PMID- 24850438
TI  - Numb chin syndrome by precursor B acute lymphoblastic leukemia.

PMID- 24850440
TI  - Advances in the treatment of childhood cancer-1944 to 1974.

PMID- 24850439
TI  - Positive relationship-intensity of response to p-phenylenediamine on patch
      testing and cross-reactions with related allergens.
AB  - BACKGROUND: Hair dye exposure is the most common cause of sensitization to p
      phenylenediamine (PPD). Cross-reactions with structurally related allergens
      occur. OBJECTIVES: It is suggested that a stronger patch test reaction (3+ rather
      than 1+) to PPD (usually tested as 1% petrolatum) is associated with an increased
      propensity for cross-reactions. In this article we will demonstrate this
      association. METHODS: Of 230 patients with allergic reactions to PPD on patch
      testing identified during 2007-2012 from clinical records, notes for 221 were
      available for review. Data were collected regarding age, sex, and grade of
      reaction [International Contact Dermatitis Research Group (ICDRG) criteria] to
      PPD. Cross-reactions with the following allergens, found in our baseline series,
      were recorded: Disperse Yellow 3, N-isopropyl-N'-phenyl-p-phenylenediamine
      (IPPD), and caine mix. Having excluded 23 doubtful reactions, the reactions from
      198 patients were further considered. RESULTS: Of the patients, 75.3% (n = 149)
      were female, and the mean age was 48.6 years (12-82 years). Of the patients
      allergic to PPD, 16.6% (n = 33) showed cross-reactions with one or more related
      allergens. Cross-reactions were seen in 16% with a grade of 1+, 14.5% with a
      grade of 2+, 28.6% with a grade of 3+ when PPD was tested 1% pet., and 50.0% when
      PPD was tested at 0.1-0.001%, arbitrarily considered to be 4+ (p = 0.02; Cramer's
      V = 0.23). CONCLUSION: An increasing likelihood of reactions to Disperse Yellow
      3, IPPD or caine mix was seen with increasing strength of patch test reaction to
      PPD. The clinical relevance of these cross-reactions is unclear.

PMID- 24850441
TI  - Are clusters important in understanding the mechanisms in atmospheric pressure
      ionization? Part 1: Reagent ion generation and chemical control of ion
      populations.
AB  - It is well documented since the early days of the development of atmospheric
      pressure ionization methods, which operate in the gas phase, that cluster ions
      are ubiquitous. This holds true for atmospheric pressure chemical ionization, as
      well as for more recent techniques, such as atmospheric pressure photoionization,
      direct analysis in real time, and many more. In fact, it is well established that
      cluster ions are the primary carriers of the net charge generated. Nevertheless,
      cluster ion chemistry has only been sporadically included in the numerous
      proposed ionization mechanisms leading to charged target analytes, which are
      often protonated molecules. This paper series, consisting of two parts, attempts
      to highlight the role of cluster ion chemistry with regard to the generation of
      analyte ions. In addition, the impact of the changing reaction matrix and the non
      thermal collisions of ions en route from the atmospheric pressure ion source to
      the high vacuum analyzer region are discussed. This work addresses such issues as
      extent of protonation versus deuteration, the extent of analyte fragmentation, as
      well as highly variable ionization efficiencies, among others. In Part 1, the
      nature of the reagent ion generation is examined, as well as the extent of
      thermodynamic versus kinetic control of the resulting ion population entering the
      analyzer region. 

PMID- 24850443
TI  - An obesity program in public schools.

PMID- 24850442
TI  - Membrane fuel cell cathode catalysts based on titanium oxide supported platinum
      nanoparticles.
AB  - The potential of platinum catalysts supported on pure, nitrogen-, or carbon-doped
      titania for application in the oxygen reduction reaction (ORR), as a cathode
      catalyst in polymer electrolyte membrane fuel cells, is investigated. The oxide
      supports are synthesized by using a sol-gel route. Modification with nitrogen and
      carbon doping is achieved by thermal decomposition of urea and the structure
      directing agent P123. Platinum nanoparticles are prepared by reduction of a
      Pt(IV) salt in ethylene glycol and subsequently immobilized on different support
      materials. Structural and electronic properties of the support materials and the
      resulting catalysts are characterized by various methods, including X-ray
      diffraction, transmission electron microscopy, and X-ray photoelectron
      spectroscopy. These results and electrochemical characterization of the support
      materials and platinum nanoparticle catalysts indicate distinct support effects
      in the catalysts. The electrocatalytic performance of these catalysts in the ORR,
      as determined in rotating ring disc electrode measurements, is promising. Also
      here, distinct support effects can be identified. Correlations with the
      structural/electronic and the electrochemical properties are discussed, as well
      as the role of metal-support interactions. 

PMID- 24850444
TI  - Process modeling of an advanced NH3 abatement and recycling technology in the
      ammonia-based CO2 capture process.
AB  - An advanced NH3 abatement and recycling process that makes great use of the waste
      heat in flue gas was proposed to solve the problems of ammonia slip, NH3 makeup,
      and flue gas cooling in the ammonia-based CO2 capture process. The rigorous rate
      based model, RateFrac in Aspen Plus, was thermodynamically and kinetically
      validated by experimental data from open literature and CSIRO pilot trials at
      Munmorah Power Station, Australia, respectively. After a thorough sensitivity
      analysis and process improvement, the NH3 recycling efficiency reached as high as
      99.87%, and the NH3 exhaust concentration was only 15.4 ppmv. Most importantly,
      the energy consumption of the NH3 abatement and recycling system was only 59.34
      kJ/kg CO2 of electricity. The evaluation of mass balance and temperature steady
      shows that this NH3 recovery process was technically effective and feasible. This
      process therefore is a promising prospect toward industrial application. 

PMID- 24850446
TI  - Introduction.

PMID- 24850445
TI  - Model-based meta-analysis for quantifying Paclitaxel dose response in cancer
      patients.
AB  - Model-based meta-analysis of dose response is a sophisticated method to guide
      dose and regimen selection. In this report, the effects of paclitaxel dose and
      regimen (weekly or every 3 weeks) on the efficacy and safety in cancer patients
      were quantified by model-based meta-analysis of 29 monotherapy trials. Logistic
      regression models were developed to assess the relationship between dose and
      objective response rate or neutropenia rate. Survival models were developed to
      assess the relationship between dose and overall survival or progression-free
      survival. Paclitaxel efficacy (e.g., objective response rate, median overall
      survival, and progression-free survival) is correlated with average dose per week
      (mg/m(2)/week), whereas safety (e.g., neutropenia rate) is correlated with dose
      per administration (mg/m(2)). Weekly paclitaxel regimen at 65-80 mg/m(2) is
      supported to have comparable to better efficacy and lower neutropenia incidence
      than an every-3-week regimen at 175 mg/m(2). 

PMID- 24850447
TI  - Synthesis of silver glyconanoparticles from new sugar-based amphiphiles and their
      catalytic application.
AB  - Oligosaccharide-based amphiphiles were readily prepared by click chemistry from
      omega-azido-hexanoic or dodecanoic acids with propargyl-functionalized
      maltoheptaose or xyloglucanoligosaccharides. These amphiphilic compounds were
      used as capping/stabilizer agents in order to obtain highly stable catalytic
      silver glyconanoparticles (Ag-GNPs) through the in situ reduction of silver
      nitrate with NaBH4. With a view to long-term storage, the stabilization was
      optimized using a multivariate approach, and the nanoparticles were characterized
      by UV-vis, TEM, SAXS, and DLS. In order to explore the functionality of the Ag
      GNPs in catalysis, a full kinetic analysis of the reduction of p-nitrophenol by
      NaBH4 in water and in water/ethanol mixtures was performed under semi
      heterogeneous and quasi-homogeneous conditions. A pseudomonomolecular surface
      reaction was performed, and the kinetic data obtained were treated according to
      the Langmuir model. The Ag-GNPs were very active, and both substrates adsorbed
      onto the surface of the nanoparticles. For comparison purposes, the reaction was
      also performed in the presence of silver-sodium dodecanoate nanoparticles, which
      showed catalytic activity similar to that of the glyconanoparticles, supporting
      the choice of the carboxyl group as the stabilizing agent, although it provided
      much lower temporal stability. Finally, by combining kinetic and water/ethanol
      surface tension data it was possible to observe the effect of the addition of the
      less polar solvent (ethanol) to the reaction medium. 

PMID- 24850449
TI  - Direct reprogramming of fibroblasts and preadipocytes into functional
      megakaryocytes.

PMID- 24850450
TI  - Plasminogen activator inhibitor-1 (PAI-1) molecule: new physiological roles and
      clinical applications.

PMID- 24850451
TI  - Conformational regulation of integrin activation in drug discovery.

PMID- 24850452
TI  - Peripheral T/NK cell lymphoma: current understanding and future perspectives.

PMID- 24850453
TI  - Impacts of new agents for multiple myeloma on development of secondary
      myelodysplastic syndrome and acute myeloid leukemia.
AB  - The use of new agents (NAs) such as bortezomib, thalidomide, and lenalidomide has
      extended the survival of patients with multiple myeloma (MM). However, whether
      long-term treatment using NAs may increase the risk of second primary
      malignancies is a concern. Three hundred and thirty-three patients with MM were
      treated at our hospital from 1998 to 2013. Additional chromosomal abnormalities
      (CAs), associated with secondary myelodysplastic syndrome/acute myeloid leukemia,
      were observed in 13 of 152 users of NAs, but in 38 of 181 non-users of NAs. The
      cumulative CA incidence was higher in non-users of NAs. The CAs frequently
      observed were 13q-, 20q-, +8 in users of NAs, while -5/5q- and -7/7q- were
      detected in non-users of NAs. The total dose and treatment period of NAs did not
      differ between CAs-positive and -negative patients. However, a higher dose of
      melphalan was observed to have been used in patients who had CAs. Longer follow
      up periods are necessary for an accurate risk assessment.

PMID- 24850454
TI  - Pagophagia in iron deficiency anemia.
AB  - The relationship between pagophagia (ice pica) and iron deficiency anemia was
      studied. All 81 patients with iron deficiency anemia defined as hemoglobin <12.0
      g/dl and ferritin level <12 ng/ml were interviewed about their habits of eating
      ice or other non-food substances. Pagophagia was defined as compulsive and
      repeated ingestion of at least one tray of ice or ice eating which was relieved
      after iron administration. Pagophagia was present in 13 patients (16.0%). All
      patients who received oral iron were periodically assessed employing a
      questionnaire on pagophagia and laboratory data. Iron therapy can cure the
      pagophagia earlier than hemoglobin recovery and repair of tissue iron deficiency.
      Although the pathogenesis of pagophagia is unclear, a biochemical approach
      involving the central nervous system might elucidate the mechanism underlying
      these abnormal behaviors.

PMID- 24850455
TI  - Successful treatment of an essential thrombocythemia patient complicated by
      Sweet's syndrome with combination of chemotherapy and lenalidomide.
AB  - A 79-year-old man had been followed up since July 2003 based on a diagnosis of
      essential thrombocythemia (ET). The patient visited our hospital after developing
      a high fever and rash in August 2010, and Sweet's syndrome was diagnosed based on
      skin biopsy results. The bone marrow aspirate showed features like those of
      myelodysplastic/myeloproliferative neoplasm (MDS/MPN, unclassifiable).
      Administration of metenolone and azacitidine was initiated in March and May 2011,
      respectively, but the rash associated with Sweet's syndrome showed exacerbation.
      Ranimustine was therefore administered starting in July 2011 to control the blood
      cell count, but the rash associated with Sweet's syndrome persisted. Combination
      therapy with lenalidomide was initiated in September 2012, and resulted in
      control of the blood cell count and marked improvement of Sweet's syndrome.

PMID- 24850456
TI  - Development of acute pure red cell aplasia after deferasirox administration in
      two cases of myelodysplastic syndrome.
AB  - Cases 1 and 2 were 55- and 68-year-old males, respectively. Both were
      administered deferasirox (DFX) because they received red blood cell transfusions
      regularly as treatment for myelodysplastic syndrome refractory anemia. DFX
      administrations were stopped on the 22nd day in case 1 and on the 78th day in
      case 2 because significantly reduced hemoglobin values and reticulocyte counts
      were observed. Bone marrow examinations showed pure red cell aplasia in both
      cases. In case 1, the reticulocyte ratio recovered to the value before drug
      administration 21 days after drug withdrawal. In case 2, it started increasing on
      the 14th day, and had recovered to the value before drug administration by the
      42nd day after drug withdrawal. Human parvovirus B19 infections were negative in
      both cases. Both cases were thought to have drug-induced pure red cell aplasia,
      probably due to DFX. This drug should be used carefully with regular follow-ups
      of the reticulocyte count.

PMID- 24850457
TI  - Long-term survival of a patient with multiple myeloma-associated severe cardiac
      AL amyloidosis after implantation of a cardioverter-defibrillator.
AB  - Cardiac involvement is by far the most relevant factor impacting poor outcomes of
      patients with systemic light-chain (AL) amyloidosis. Median survival of patients
      with symptomatic cardiac AL amyloidosis is less than 6 months. Approximately two
      thirds of these patients die suddenly due to ventricular arrhythmias and
      electromechanical dissociation. We report a 56-year-old female with very severe
      cardiac AL amyloidosis (NT-proBNP 13,355 ng/l, troponin T 0.16 MUg/l, and
      systolic blood pressure 100 mmHg), who was successfully treated with diuretics
      and an implantable cardioverter-defibrillator (ICD) and has survived for more
      than 4 years, to date. During the 4-year period after receiving the ICD, she
      experienced several episodes of sustained ventricular tachycardia and ventricular
      fibrillation, all successfully terminated by anti-tachycardia pacing or
      electrical shock. The benefit of ICD for cardiac AL amyloidosis is unclear since
      there have been only a few reports of successful use of this therapy for patients
      with cardiac AL amyloidosis. Recently, new treatment options for AL amyloidosis,
      such as bortezomib and lenalidomide, have shown high response rates and improved
      outcomes. It is important to identify those cardiac amyloidosis patients who
      might be more likely to benefit from ICD implantation.

PMID- 24850458
TI  - Cerebral toxoplasmosis after umbilical cord blood transplantation diagnosed by
      the detection of anti-toxoplasma specific IgM antibody in cerebrospinal fluid.
AB  - Cerebral toxoplasmosis is a rare, potentially fatal, complication of
      hematopoietic cell transplantation. Early definitive diagnosis is very difficult
      and it may be associated with a poor prognosis. Herein, we describe a 60-year-old
      woman who developed cerebral toxoplasmosis after cord blood transplantation for
      myelodysplastic syndrome. During treatment with tacrolimus and methylprednisolone
      for relapsed grade 2 acute gut GVHD, fever and disturbance of consciousness
      occurred on day 210. Brain MRI showed multiple ring-enhancing nodular lesions in
      the thalamus, basal ganglia, brainstem, and subcortical white matter.
      Cerebrospinal fluid (CSF) assessment revealed elevations of both anti-to-xoplasma
      IgM and IgG, which were also elevated in serum, but no evidence of other
      infections or malignancies. Notably, the IgM level was higher in the CSF than in
      serum. Thus, cerebral toxoplasmosis was diagnosed. Soon after administration of
      oral sulfamethoxazole/trimethoprim and intravenous clindamycin in combination
      with short-term dexamethasone for the cerebral edema, her symptoms and signs
      began to improve. On day 229, both IgM and IgG titers in CSF had clearly
      decreased but remained essentially constant in serum. She was discharged without
      clinically significant neurological disorders. This case suggests that CSF
      specific anti-toxoplasma IgM titers might be useful for early diagnosis of
      cerebral toxoplasmosis after transplantation.

PMID- 24850459
TI  - Complete remission achieved in a multiple myeloma patient with elevated serum KL
      6 level by a combination regimen with bortezomib, cyclophosphamide, and
      dexamethasone.
AB  - A 79-year-old woman suffering from double vision after a 4-year history of MGUS
      was referred to our hospital. MRI revealed that she had three intracranial
      plasmacytoma masses and one spinal plasmacytoma mass. Bone marrow aspirates
      showed 52.4% plasma cell infiltration and immunoelectrophoresis identified serum
      IgG-M protein, leading to a diagnosis of IgG-type multiple myeloma. IgG was
      elevated to 3,355 mg/dl and urine type Bence-Jones protein was positive. KL-6, a
      membrane-bound glycoprotein encoded by Mucin 1 and a marker of interstitial
      pneumonia, was also elevated to 1,409 mg/dl, but computed tomography of the lungs
      revealed no obvious pulmonary lesions. Previously reported studies showing that
      myeloma patients with elevated KL-6 might have a poor prognosis prompted us to
      treat this patient with a three-drug (bortezomib, cyclophosphamide, and
      dexamethasone: VCD) combination regimen. When 6 cycles of the regimen had been
      completed, no M-protein was detectable in her serum. Furthermore, kappa free
      light chain had significantly decreased from 12,700 to 24.8 mg/l. In addition,
      (18)F-FDG PET/CT revealed reduced mass sizes and no (18)F-FDG uptakes by
      plasmacytomas. Thus, she was defined as having achieved a stringent complete
      remission (sCR). We therefore concluded that the VCD combination regimen was
      highly effective in this multiple myeloma patient with KL-6 elevation.

PMID- 24850460
TI  - Hairy cell leukemia accompanied by Evans syndrome.
AB  - We report a case of Western type hairy cell leukemia (HCL), a very rare leukemia
      in Japan. In this malignancy, leukemic cells in a peripheral blood film may be
      missed due in part to accompanying pancytopenia and in part to loss of typical
      cytoplasmic projections if prepared in a conventional Japanese way using forced
      air-drying. Our present patient also had a variety of autoantibodies and the
      clinical picture was primarily that of Evans syndrome (ES), suggesting disturbed
      immune responses associated with the HCL. Although HCL accompanied by either AIHA
      or ITP has been reported, the occurrence of ES in HCL is extremely rare.

PMID- 24850462
TI  - Transition metal complexes with bioactive ligands: mechanisms for selective
      ligand release and applications for drug delivery.
AB  - The unique properties of transition metal complexes, such as environment
      responsive ligand exchange kinetics, diverse photochemical and photophysical
      properties, and the ability to form specific interactions with biomolecules, make
      them interesting platforms for selective drug delivery. This minireview will
      focus on recent examples of rationally designed complexes with bioactive ligands,
      exploring the different roles of the metal, and mechanisms of ligand release.
      Developments in the techniques used to study the mechanisms of action of metal
      drug complexes will also be discussed, including X-ray protein crystallography,
      fluorescence lifetime imaging, and X-ray absorption spectroscopy. 

PMID- 24850466
TI  - Synthesis of isatins by I2/TBHP mediated oxidation of indoles.
AB  - An I2/TBHP mediated oxidation of commercially available indoles has been
      developed, which affords isatins in moderate to good yields. 

PMID- 24850465
TI  - A fish-based diet intervention improves endothelial function in postmenopausal
      women with type 2 diabetes mellitus: a randomized crossover trial.
AB  - OBJECTIVE: The beneficial effects of fish and n-3 polyunsaturated fatty acids
      (PUFAs) consumption on atherosclerosis have been reported in numerous
      epidemiological studies. However, to the best of our knowledge, the effects of a
      fish-based diet intervention on endothelial function have not been investigated.
      Therefore, we studied these effects in postmenopausal women with type 2 diabetes
      mellitus (T2DM). MATERIALS/METHODS: Twenty-three postmenopausal women with T2DM
      were assigned to two four-week periods of either a fish-based diet (n-3 PUFAs ?
      3.0 g/day) or a control diet in a randomized crossover design. Endothelial
      function was measured with reactive hyperemia using strain-gauge plethysmography
      and compared with the serum levels of fatty acids and their metabolites.
      Endothelial function was determined with peak forearm blood flow (Peak), duration
      of reactive hyperemia (Duration) and flow debt repayment (FDR). RESULTS: A fish
      based dietary intervention improved Peak by 63.7%, Duration by 27.9% and FDR by
      70.7%, compared to the control diet. Serum n-3 PUFA levels increased after the
      fish-based diet period and decreased after the control diet, compared with the
      baseline (1.49 vs. 0.97 vs. 1.19 mmol/l, p < 0.0001). There was no correlation
      between serum n-3 PUFA levels and endothelial function. An increased ratio of
      epoxyeicosatrienoic acid/dihydroxyeicosatrienoic acid was observed after a fish
      based diet intervention, possibly due to the inhibition of the activity of
      soluble epoxide hydrolase. CONCLUSIONS: A fish-based dietary intervention
      improves endothelial function in postmenopausal women with T2DM. Dissociation
      between the serum n-3 PUFA concentration and endothelial function suggests that
      the other factors may contribute to this phenomenon.

PMID- 24850467
TI  - Guest Editor's Foreword.

PMID- 24850468
TI  - The adherence to ASAS classification criteria and to ASAS recommendations for the
      use of anti-TNH-alpha agents in axial spondyloarthritis.
AB  - OBJECTIVES: To determine the adherence of practicing rheumatologists, before and
      after an educational project, to Assessment of SpondyloArthritis international
      Society (ASAS) classification criteria and to ASAS recommendations for the use of
      anti-tumor necrosis factor (TNF)-alpha agents in patients with axial
      spondyloarthritis (SpA). METHODS: The project involved 53 rheumatologists
      attending 2 educational meetings on an update of SpA. Each meeting included
      interactive sessions on 1) clinical cases, 2) clinimetric evaluation, including
      ASAS core set for daily practice and 3) imaging. Diagnostic and therapeutic
      approach of each participant was tested using short clinical cases, obtained from
      real-life rheumatology settings, at the beginning and at the end of this
      educational project. Each case for diagnostic (n=10) or therapeutic purpose
      (n=10) had 10 possible choices. Each participant gave a score from 0 (total
      disagreement) to 10 (total agreement) for each choice. RESULTS: At baseline, the
      rheumatologists had an excellent agreement with ASAS classification criteria for
      axial SpA and anti-TNF-alpha treatment according to ASAS recommendations with a
      further significant improvement after the educational programme. In axial SpA
      cases with acute anterior uveitis (AU) or Crohn's disease, anti-TNF-alpha
      treatment was indicated mainly as monoclonal anti-TNF antibody. In presence of
      elevated levels of CRP, anti-TNF option has been considered useful. CONCLUSIONS:
      Practicing rheumatologists had a satisfying adherence to ASAS classification
      criteria and to ASAS recommendations for the use of anti-TNF-alpha agents for
      patients with axial SpA. Extra-articular manifestations and other variables might
      play a role in the decision-process of the management of axial SpA.

PMID- 24850470
TI  - Pneumocephalus following the minimally invasive hematoma aspiration and
      thrombolysis for ICH.
AB  - INTRODUCTION: The objective of this study was to clarify whether pneumocephalus
      occurred and affected the outcome following minimally invasive hematoma
      aspiration and thrombolysis for intracerebral hemorrhage (ICH). MATERIALS AND
      METHODS: A prospective case note review on all ICH patients treated with the
      micro-invasive procedure presenting to our division from 2006 to 2011 was
      conducted. Demographic, clinical, and outcome data were documented; head CT scans
      were applied postoperatively to identify the intracranial air collection. The ICH
      victims with pneumocephalus were included into Group A and the others into Group
      B. A multi-variant analysis was performed between Groups A and B to examine the
      effect of pneumocephalus on the prognosis. RESULTS: Data were collected on a
      total of 134 cases in this study, among whom 72.38% developed pneumocephalus
      postoperatively. No significant difference was demonstrated in terms of the
      preoperative and postoperative hematoma volume, Glasgow Coma Scale (GCS) score,
      middle line shift (MLS), and 30-day mortality rate between Groups A and B,
      respectively. Moreover, the long-term outcome rated by GCS of these two groups
      was also similar. Logistic regression analysis indicated double-needle puncture
      be an independent risk factor for both postoperative pneumocephalus (OR, 2.478;
      95% CI, 1.010-6.080; P = 0.045) and its degree (OR, 11.84; 95%CI, 4.141-30.208; P
      < 0.001). CONCLUSION: The present study shows that pneumocephalus is common
      following the minimally invasive hematoma aspiration and thrombolysis for ICH but
      may not affect the outcome. And double-needle puncture may be the risk factor for
      pneumocephalus.

PMID- 24850471
TI  - Functional hyposplenism is an important and underdiagnosed immunodeficiency
      condition in children.
AB  - AIM: Few studies have focused on paediatric hyposplenism/asplenism, in which
      splenic phagocytic activity is diminished or absent in an anatomically present
      spleen. This study aimed to evaluate clinical findings, laboratory tests and
      prognosis of children with functional hyposplenism/asplenism. METHODS: The study
      group comprised 74 children who had liver/spleen technetium-99m sulphur colloid
      scintigraphy from 2002 to 2008. Information collected included demographic
      features, background diseases, blood smear findings, indications for scintigraphy
      and outcome. Children with functional hyposplenism were followed until 2012.
      RESULTS: We found that 34 patients had functional hyposplenism/asplenism. The
      main indications for scintigraphy in the hyposplenic patients were persistent
      thrombocytosis and recurrent infections. Associated conditions included
      immunodeficiencies, autoimmune diseases, malignancies and genetic disorders. Main
      infections were sinopulmonary infections, bacteraemia and sepsis. The major
      pathogens were Streptococcus pneumoniae and Haemophilus influenza group A. There
      was no correlation between the presence of Howell-Jolly bodies in blood smear
      with clinical disease severity or scintigraphic findings. Repeated scintigraphy
      showed spontaneous normalisation in 40% of patients. CONCLUSION: Functional
      hyposplenism is an important and underdiagnosed immunodeficiency condition in
      children, associated with various clinical conditions including prolonged
      unexplained thrombocytosis, immune deficiency and autoimmunity. Technetium-99m
      sulphur colloid scintigraphy is the method of choice for evaluating splenic
      function.

PMID- 24850472
TI  - Therapeutic doses of multipotent stromal cells from minimal adipose tissue.
AB  - Low yield of adult adipose-derived multipotent stromal cells (ASC) can limit
      autologous cell therapy in individuals with minimal adipose tissue. In this
      study, ASC isolation was optimized from approximately 0.2 g of feline epididymal
      adipose tissue for a treatment dose of 10(6)-10(7) ASCs/kg. The ASC yield was
      determined for three digestions, 0.1 % collagenase in medium for 30 min
      (Classic), 0.3 % collagenase in buffer for 30 min (New) and 0.3 % collagenase in
      buffer for 1 h (Hour). After isolation by the new tissue digestion, continuously
      cultured ASCs (fresh) and cells recovered and expanded after cryostorage at P0
      (revitalized) were characterized up to cell passage (P) 5. Outcomes included CD9,
      CD29, CD44, CD90 and CD105 expression, cell doublings and doubling times,
      fibroblastic, adipogenic and osteogenic colony forming unit (CFU) frequency
      percentages and lineage-specific target gene expression after induction. The New
      digestion had the highest CFU yield, and about 7x10(6) ASCs/kg were available
      within three cell passages (P2). Compared to earlier passages, target surface
      antigen expression was lowest in fresh P5 cells, and fresh and revitalized P3-5
      cells had slower expansion. Fresh and revitalized P1 ASCs had higher CFU
      frequency percentages and lineage-specific gene expression than P3. The New
      method described in this study was most efficient for feline epididymal ASC
      isolation and did not alter in vitro cell behavior. Fresh and revitalized P0-P2
      feline ASCs may be most effective for preclinical and clinical trials. This study
      offers a potential option for ASC isolation from limited adipose tissue resources
      across species. 

PMID- 24850475
TI  - Nearly amorphous Mo-N gratings for ultimate resolution in extreme ultraviolet
      interference lithography.
AB  - We present fabrication and characterization of high-resolution and nearly
      amorphous Mo1 - xNx transmission gratings and their use as masks for extreme
      ultraviolet (EUV) interference lithography. During sputter deposition of Mo,
      nitrogen is incorporated into the film by addition of N2 to the Ar sputter gas,
      leading to suppression of Mo grain growth and resulting in smooth and homogeneous
      thin films with a negligible grain size. The obtained Mo0.8N0.2 thin films, as
      determined by x-ray photoelectron spectroscopy, are characterized to be nearly
      amorphous using x-ray diffraction. We demonstrate a greatly reduced Mo0.8N0.2
      grating line edge roughness compared with pure Mo grating structures after e-beam
      lithography and plasma dry etching. The amorphous Mo0.8N0.2 thin films retain, to
      a large extent, the benefits of Mo as a phase grating material for EUV
      wavelengths, providing great advantages for fabrication of highly efficient
      diffraction gratings with extremely low roughness. Using these grating masks,
      well-resolved dense lines down to 8 nm half-pitch are fabricated with EUV
      interference lithography. 

PMID- 24850474
TI  - Antitumor effect of nuclear factor-kappaB decoy transfer by mannose-modified
      bubble lipoplex into macrophages in mouse malignant ascites.
AB  - Patients with malignant ascites (MAs) display several symptoms, such as dyspnea,
      nausea, pain, and abdominal tenderness, resulting in a significant reduction in
      their quality of life. Tumor-associated macrophages (TAMs) play a crucial role in
      MA progression. Because TAMs have a tumor-promoting M2 phenotype, conversion of
      the M2 phenotypic function of TAMs would be promising for MA treatment. Nuclear
      factor-kappaB (NF-kappaB) is a master regulator of macrophage polarization. Here,
      we developed targeted transfer of a NF-kappaB decoy into TAMs by ultrasound (US)
      responsive, mannose-modified liposome/NF-kappaB decoy complexes (Man-PEG bubble
      lipoplexes) in a mouse peritoneal dissemination model of Ehrlich ascites
      carcinoma. In addition, we investigated the effects of NF-kappaB decoy
      transfection into TAMs on MA progression and mouse survival rates.
      Intraperitoneal injection of Man-PEG bubble lipoplexes and US exposure
      transferred the NF-kappaB decoy into TAMs effectively. When the NF-kappaB decoy
      was delivered into TAMs by this method in the mouse peritoneal dissemination
      model, mRNA expression of the Th2 cytokine interleukin (IL)-10 in TAMs was
      decreased significantly. In contrast, mRNA levels of Th1 cytokines (IL-12, tumor
      necrosis factor-alpha, and IL-6) were increased significantly. Moreover, the
      expression level of vascular endothelial growth factor in ascites was suppressed
      significantly, and peritoneal angiogenesis showed a reduction. Furthermore, NF
      kappaB decoy transfer into TAMs significantly decreased the ascitic volume and
      number of Ehrlich ascites carcinoma cells in ascites, and prolonged mouse
      survival. In conclusion, we transferred a NF-kappaB decoy efficiently by Man-PEG
      bubble lipoplexes with US exposure into TAMs, which may be a novel approach for
      MA treatment. 

PMID- 24850478
TI  - Prenatal exposure to narcotics- what is the risk of long-term damage to the
      central nervous system?

PMID- 24850482
TI  - Risk of myocardial infarction and stroke in bipolar disorder: a systematic review
      and exploratory meta-analysis.
AB  - OBJECTIVE: To review the evidence on and estimate the risk of myocardial
      infarction and stroke in bipolar disorder. METHOD: A systematic search using
      MEDLINE, EMBASE, PsycINFO, Web of Science, Scopus, Cochrane Database of
      Systematic Reviews, and bibliographies (1946 - May, 2013) was conducted. Case
      control and cohort studies of bipolar disorder patients age 15 or older with
      myocardial infarction or stroke as outcomes were included. Two independent
      reviewers extracted data and assessed quality. Estimates of effect were
      summarized using random-effects meta-analysis. RESULTS: Five cohort studies
      including 13 115 911 participants (27 092 bipolar) were included. Due to the use
      of registers, different statistical methods, and inconsistent adjustment for
      confounders, there was significant methodological heterogeneity among studies.
      The exploratory meta-analysis yielded no evidence for a significant increase in
      the risk of myocardial infarction: [relative risk (RR): 1.09, 95% CI 0.96-1.24, P
      = 0.20; I(2)  = 6%]. While there was evidence of significant study heterogeneity,
      the risk of stroke in bipolar disorder was significantly increased (RR 1.74, 95%
      CI 1.29-2.35; P = 0.0003; I(2)  = 83%). CONCLUSION: There may be a differential
      risk of myocardial infarction and stroke in patients with bipolar disorder.
      Confidence in these pooled estimates was limited by the small number of studies,
      significant heterogeneity and dissimilar methodological features.

PMID- 24850484
TI  - Association between resting heart rate across the life course and all-cause
      mortality: longitudinal findings from the Medical Research Council (MRC) National
      Survey of Health and Development (NSHD).
AB  - BACKGROUND: Resting heart rate (RHR) is an independent risk factor for mortality.
      Nevertheless, it is unclear whether elevations in childhood and mid-adulthood
      RHR, including changes over time, are associated with mortality later in life. We
      sought to evaluate the association between RHR across the life course, along with
      its changes and all-cause mortality. METHODS: We studied 4638 men and women from
      the Medical Research Council (MRC) National Survey of Health and Development
      (NSHD) cohort born during 1 week in 1946. RHR was obtained during childhood at
      ages 6, 7 and 11, and in mid-adulthood at ages 36 and 43. Using multivariable Cox
      regression, we calculated the HR for incident mortality according to RHR measured
      at each time point, along with changes in mid-adulthood RHR. RESULTS: At age 11,
      those in the top fifth of the RHR distribution (>=97 bpm) had an increased
      adjusted hazard of 1.42 (95% CI 1.04 to 1.93) for all-cause mortality. A higher
      adjusted risk (HR, 95% CI 2.17, 1.40 to 3.36) of death was also observed for
      those in the highest fifth (>=81 bpm) at age 43. For a >25 bpm increased change
      in the RHR over the course of 7 years (age 36-43), the adjusted hazard was
      elevated more than threefold (HR, 95% CI 3.26, 1.54 to 6.90). After adjustment,
      RHR at ages 6, 7 and 36 were not associated with all-cause mortality.
      CONCLUSIONS: Elevated RHR during childhood and midlife, along with greater
      changes in mid-adulthood RHR, are associated with an increased risk of all-cause
      mortality.

PMID- 24850485
TI  - Antecollis and levodopa-responsive parkinsonism are late features of Dravet
      syndrome.

PMID- 24850486
TI  - Recurrent thromboembolic events after ischemic stroke in patients with cancer.
AB  - OBJECTIVE: To determine the cumulative rate and characteristics of recurrent
      thromboembolic events after acute ischemic stroke in patients with cancer.
      METHODS: We retrospectively identified consecutive adult patients with active
      systemic cancer diagnosed with acute ischemic stroke at a tertiary-care cancer
      center from 2005 through 2009. Two neurologists independently reviewed all
      electronic records to ascertain the composite outcome of recurrent ischemic
      stroke, myocardial infarction, systemic embolism, TIA, or venous thromboembolism.
      Kaplan-Meier statistics were used to determine cumulative outcome rates. In
      exploratory analyses, Cox proportional hazard analysis was used to evaluate
      potential independent associations between a priori selected clinical factors and
      recurrent thromboembolic events. RESULTS: Among 263 study patients, complete
      follow-up until death was available in 230 (87%). Most patients had an
      adenocarcinoma as their underlying cancer (60%) and had systemic metastases
      (69%). Despite a median survival of 84 days (interquartile range 24-419 days), 90
      patients (34%; 95% confidence interval 28%-40%) had 117 recurrent thromboembolic
      events, consisting of 57 cases of venous thromboembolism, 36 recurrent ischemic
      strokes, 13 myocardial infarctions, 10 cases of systemic embolism, and one TIA.
      Kaplan-Meier rates of recurrent thromboembolism were 21%, 31%, and 37% at 1, 3,
      and 6 months, respectively; cumulative rates of recurrent ischemic stroke were
      7%, 13%, and 16%. Adenocarcinoma histology (hazard ratio 1.65, 95% confidence
      interval 1.02-2.68) was independently associated with recurrent thromboembolism.
      CONCLUSIONS: Patients with acute ischemic stroke in the setting of active cancer
      (especially adenocarcinoma) face a substantial short-term risk of recurrent
      ischemic stroke and other types of thromboembolism.

PMID- 24850487
TI  - Prehospital stroke scales in urban environments: a systematic review.
AB  - OBJECTIVE: To identify and compare the operating characteristics of existing
      prehospital stroke scales to predict true strokes in the hospital. METHODS: We
      searched MEDLINE, EMBASE, and CINAHL databases for articles that evaluated the
      performance of prehospital stroke scales. Quality of the included studies was
      assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. We
      abstracted the operating characteristics of published prehospital stroke scales
      and compared them statistically and graphically. RESULTS: We retrieved 254
      articles from MEDLINE, 66 articles from EMBASE, and 32 articles from CINAHL Plus
      database. Of these, 8 studies met all our inclusion criteria, and they studied
      Cincinnati Pre-Hospital Stroke Scale (CPSS), Los Angeles Pre-Hospital Stroke
      Screen (LAPSS), Melbourne Ambulance Stroke Screen (MASS), Medic Prehospital
      Assessment for Code Stroke (Med PACS), Ontario Prehospital Stroke Screening Tool
      (OPSS), Recognition of Stroke in the Emergency Room (ROSIER), and Face Arm Speech
      Test (FAST). Although the point estimates for LAPSS accuracy were better than
      CPSS, they had overlapping confidence intervals on the symmetric summary receiver
      operating characteristic curve. OPSS performed similar to LAPSS whereas MASS, Med
      PACS, ROSIER, and FAST had less favorable overall operating characteristics.
      CONCLUSIONS: Prehospital stroke scales varied in their accuracy and missed up to
      30% of acute strokes in the field. Inconsistencies in performance may be due to
      sample size disparity, variability in stroke scale training, and divergent
      provider educational standards. Although LAPSS performed more consistently,
      visual comparison of graphical analysis revealed that LAPSS and CPSS had similar
      diagnostic capabilities.

PMID- 24850488
TI  - Expanding the phenotypic spectrum of TUBB4A-associated hypomyelinating
      leukoencephalopathies.
AB  - OBJECTIVE: We performed whole-exome sequencing analysis of patients with
      genetically unsolved hypomyelinating leukoencephalopathies, identifying 8
      patients with TUBB4A mutations and allowing the phenotypic spectrum of TUBB4A
      mutations to be investigated. METHODS: Fourteen patients with hypomyelinating
      leukoencephalopathies, 7 clinically diagnosed with hypomyelination with atrophy
      of the basal ganglia and cerebellum (H-ABC), and 7 with unclassified
      hypomyelinating leukoencephalopathy, were analyzed by whole-exome sequencing. The
      effect of the mutations on microtubule assembly was examined by mapping altered
      amino acids onto 3-dimensional models of the alphabeta-tubulin heterodimer.
      RESULTS: Six heterozygous missense mutations in TUBB4A, 5 of which are novel,
      were identified in 8 patients (6/7 patients with H-ABC [the remaining patient is
      an atypical case] and 2/7 patients with unclassified hypomyelinating
      leukoencephalopathy). In 4 cases with parental samples available, the mutations
      occurred de novo. Analysis of 3-dimensional models revealed that the p.Glu410Lys
      mutation, identified in patients with unclassified hypomyelinating
      leukoencephalopathy, directly impairs motor protein and/or microtubule-associated
      protein interactions with microtubules, whereas the other mutations affect
      longitudinal interactions for maintaining alphabeta-tubulin structure, suggesting
      different mechanisms in tubulin function impairment. In patients with the
      p.Glu410Lys mutation, basal ganglia atrophy was unobserved or minimal although
      extrapyramidal features were detected, suggesting its functional impairment.
      CONCLUSIONS: TUBB4A mutations cause typical H-ABC. Furthermore, TUBB4A mutations
      associate cases of unclassified hypomyelinating leukoencephalopathies with
      morphologically retained but functionally impaired basal ganglia, suggesting that
      TUBB4A-related hypomyelinating leukoencephalopathies encompass a broader clinical
      spectrum than previously expected. Extrapyramidal findings may be a key for
      consideration of TUBB4A mutations in hypomyelinating leukoencephalopathies.

PMID- 24850489
TI  - Are prehospital stroke scales better than a coin toss at predicting acute stroke?

PMID- 24850490
TI  - Risk of recurrent thromboembolic phenomena after ischemic stroke in patients with
      malignancy.

PMID- 24850491
TI  - Factors associated with recovery from acute optic neuritis in patients with
      multiple sclerosis.
AB  - OBJECTIVE: To identify clinical and demographic features associated with the
      severity and recovery from acute optic neuritis (AON) episodes in patients with
      multiple sclerosis (MS). METHODS: Adult (n = 253) and pediatric (n = 38) patients
      whose first symptom was AON were identified from our MS database. Severity
      measured by loss of visual acuity (mild attack <=20/40, moderate attack 20/50
      20/190, and severe attack >=20/200) and recovery in visual acuity at 1 year after
      the attack (complete recovery <=20/20, fair recovery 20/40, and poor recovery
      >=20/50) were recorded. Demographic and clinical features associated with attack
      severity and recovery were identified using proportional odds logistic
      regression. For another group of patients, blood samples were available within 6
      months of an AON attack. In this group, the impact of vitamin D level on the
      severity/recovery was also assessed. RESULTS: Men (adjusted odds ratio [OR] =
      2.28, p = 0.03) and subjects with severe attacks (adjusted OR = 5.24, p < 0.001)
      had worse recovery. AON severity was similar between the pediatric and adult
      subjects, but recovery was significantly better in pediatric subjects in the
      unadjusted analysis (p = 0.041) and the analysis adjusted for sex (p = 0.029).
      Season-adjusted vitamin D level was significantly associated with attack severity
      (OR for 10-U increase in vitamin D level = 0.47; 95% confidence interval: 0.32,
      0.68; p < 0.001). Vitamin D level was not associated with recovery from the
      attack (p = 0.98) in univariate analysis or after accounting for attack severity
      (p = 0.10). CONCLUSION: Vitamin D levels affect AON severity, whereas younger
      age, attack severity, and male sex affect AON recovery. Underlying mechanisms and
      potential therapeutic targets may identify new measures to mitigate disability
      accrual in MS.

PMID- 24850492
TI  - Effects of APOE epsilon4, age, and HIV on glial metabolites and cognitive
      deficits.
AB  - OBJECTIVE: We aimed to evaluate the combined effects of HIV and APOE epsilon4
      allele(s) on glial metabolite levels, and on known cognitive deficits associated
      with either condition, across the ages. METHODS: One hundred seventy-seven
      participants, primarily of white and mixed race (97 seronegative subjects: aged
      44.7 +/- 1.3 years, 85 [87.6%] men, 28 [28.9%] APOE epsilon4+; 80 HIV+ subjects:
      aged 47.3 +/- 1.1 years, 73 [91.3%] men, 23 [28.8%] APOE epsilon4+), were
      assessed cross-sectionally for metabolite concentrations using proton magnetic
      resonance spectroscopy in 4 brain regions and for neuropsychological performance.
      RESULTS: Frontal white matter myo-inositol was elevated in subjects with HIV
      across the age span but showed age-dependent increase in seronegative subjects,
      especially in APOE epsilon4+ carriers. In contrast, only seronegative APOE
      epsilon4+ subjects showed elevated myo-inositol in parietal cortex. All APOE
      epsilon4+ subjects had lower total creatine in basal ganglia. While all HIV
      subjects showed greater cognitive deficits, HIV+ APOE epsilon4+ subjects had the
      poorest executive function, fluency memory, and attention/working memory. Higher
      myo-inositol levels were associated with poorer fine motor function across all
      subjects, slower speed of information processing in APOE epsilon4+ subjects, and
      worse fluency in HIV+ APOE epsilon4+ subjects. CONCLUSIONS: In frontal white
      matter of subjects with HIV, the persistent elevation and lack of normal age
      dependent increase in myo-inositol suggest that persistent glial activation
      attenuated the typical antagonistic pleiotropic effects of APOE epsilon4 on
      neuroinflammation. APOE epsilon4 negatively affects energy metabolism in brain
      regions rich in dopaminergic synapses. The combined effects of HIV infection and
      APOE epsilon4 may lead to greater cognitive deficits, especially in those with
      greater neuroinflammation. APOE epsilon4 allele(s) may be a useful genetic marker
      to identify white and mixed-race HIV subjects at risk for cognitive decline.

PMID- 24850493
TI  - Large-scale synthesis of reduced graphene oxides with uniformly coated
      polyaniline for supercapacitor applications.
AB  - We report an effective route for the preparation of layered reduced graphene
      oxide (rGO) with uniformly coated polyaniline (PANI) layers. These nanocomposites
      are synthesized by chemical oxidative polymerization of aniline monomer in the
      presence of layered rGO. SEM, TEM, X-ray photoelectron spectroscopy (XPS), FTIR,
      and Raman spectroscopy analysis results demonstrated that reduced graphene oxide
      polyaniline (rGO-PANI) nanocomposites are successfully synthesized. Because of
      synergistic effects, rGO-PANI nanocomposites prepared by this approach exhibit
      excellent capacitive performance with a high specific capacitance of 286 F g(-1)
      and high cycle reversibility of 94 % after 2000 cycles. 

PMID- 24850494
TI  - Theoretical study of the gas-phase thermolysis of 3-methyl-1,2,4,5-tetroxane.
AB  - Cyclic organic peroxides are a broad and highly sought-after class of peroxide
      compounds that present high reactivity and even explosive character. The
      unusually high reactivity of these peroxides can generally be attributed to the
      rupture of O-O bonds. Cyclic diperoxides are a very interesting series of
      substituted compounds in which tetroxane is the most prominent member. Gas-phase
      thermolysis of the simplest substituted member of the series [3-methyl-1,2,4,5
      tetroxane or methylformaldehyde diperoxide (MFDP)] has been observed to yield one
      acetaldehyde, one formaldehyde, and one oxygen molecule as reaction products. DFT
      at the 6-311 + G** level of theory using the BHANDHLYP correlation-exchange
      functional was applied via the Gaussian09 program to calculate the critical
      points of the potential energy surface (PES) of this reaction. Equatorial and
      axial isomers were studied. The singlet state PES of MFDP was calculated, and an
      open diradical structure was found to be the first intermediate in a stepwise
      reaction. Two PESs were subsequently obtained: singlet state (S) and triplet
      state (T) PESs. After that, two alternative stepwise reactions were found to be
      possible: 1) one in which either an acetaldehyde, or 2) formaldehyde molecule is
      initially formed. For second one, exothermic reactions were observed for both the
      S and T PESs. The reaction products include a oxygen molecule in either S or T
      state, with the T reaction being the most exothermic. When calculations were
      performed at the CASSCF(10,10)/6-311 + G** level, spin-orbit coupling permitted S
      to T crossing at the open diradical intermediate stage, a non-adiabatic reaction
      was observed, and lower activation energies and higher exothermicity were
      generally seen for the T PES than for the S PES. These results were compared with
      the corresponding results for tetroxane. The spin-orbit coupling of MFDP and
      tetroxane yielded identical values, so it appears that the methyl substituent
      does not have any effect on this coupling. 

PMID- 24850496
TI  - Sensitive detection of trypsin using liquid-crystal droplet patterns modulated by
      interactions between poly-L-lysine and a phospholipid monolayer.
AB  - Liquid-crystal (LC) droplet patterns are formed on a glass slide by evaporating a
      solution of nematic LC dissolved in heptane. In the presence of an anionic
      phospholipid, 1,2-dioleoyl-sn-glycero-3-phospho-rac-(1-glycerol) (DOPG), the LCs
      display a dark cross pattern, indicating a homeotropic orientation. When LC
      patterns are incubated with an aqueous mixture of DOPG and poly-L-lysine (PLL),
      there is a transition in the LC pattern from a dark cross to a bright fan shape
      due to the electrostatic interaction between DOPG and PLL. Known to catalyze the
      hydrolysis of PLL into oligopeptide fragments, trypsin is preincubated with PLL,
      significantly decreasing the interactions between PLL and DOPG. LCs adopt a
      perpendicular orientation at the water-LC droplet interface, which gives rise to
      a dark cross pattern. This optical response of LC droplets is the basis for a
      quick and sensitive biosensor for trypsin. 

PMID- 24850495
TI  - Analyses of cobalt-ligand and potassium-ligand bond lengths in metalloproteins:
      trends and patterns.
AB  - Cobalt and potassium are biologically important metal elements that are present
      in a large array of proteins. Cobalt is mostly found in vivo associated with a
      corrin ring, which represents the core of the vitamin B12 molecule. Potassium is
      the most abundant metal in the cytosol, and it plays a crucial role in
      maintaining membrane potential as well as correct protein function. Here, we
      report a thorough analysis of the geometric properties of cobalt and potassium
      coordination spheres that was performed with high resolution on a representative
      set of structures from the Protein Data Bank and complemented by quantum
      mechanical calculations realized at the DFT level of theory (B3LYP/ SDD) on
      mononuclear model systems. The results allowed us to draw interesting conclusions
      on the structural characteristics of both Co and K centers, and to evaluate the
      importance of effects such as their association energies and intrinsic
      thermodynamic stabilities. Overall, the results obtained provide useful data for
      enhancing the atomic models normally applied in theoretical and computational
      studies of Co or K proteins performed at the quantum mechanical level, and for
      developing molecular mechanical parameters for treating Co or K coordination
      spheres in molecular mechanics or molecular dynamics studies. 

PMID- 24850497
TI  - Reproductive Tract Infections in Rural Vietnam, Women's Knowledge, and Health
      Seeking Behavior: A Cross-Sectional Study.
AB  - We interviewed 1,805 women in a rural setting in Vietnam with the aim of
      investigating women's knowledge regarding reproductive tract infections (RTIs)
      and their health-seeking behavior. We found that women's overall knowledge was
      poor. Furthermore, only one-third of the symptomatic women sought health care.
      RTIs affect millions of women globally each year. Most vulnerable are women in
      low- and middle-income countries where poverty and gender inequities affect their
      access to health care services. Findings from our study can be used in similar
      rural settings worldwide to understand and manage the widespread problem of RTIs.

PMID- 24850498
TI  - [Prevention in the elderly: position paper on pneumococcal vaccinations. Results
      of an expert workshop on 15 November 2013 in Cologne, Germany].
AB  - Infections due to pneumococci especially in the elderly are vastly
      underestimated, e.g., because non-invasive infections such as pneumonia may
      appear with only few symptoms. Sequential vaccination with the pneumococcal
      conjugate vaccine PCV13, followed by the 23-valent polysaccharide vaccine, is
      considered as the best preventive measure for individual protection, even though
      clinical study data demonstrating the efficacy of this sequence are not yet
      available. Increase of "awareness" by use of computer-based reminder functions
      may result in a significant improvement of vaccination compliance. 

PMID- 24850499
TI  - Prognosis of myopericarditis as determined from previously published reports.
AB  - BACKGROUND: The prognosis of pericarditis with concomitant myocarditis,
      especially in the setting of troponin elevation, is a reason for concern because
      it could imply an adverse outcome. METHODS: We performed a comprehensive Medline
      search of all publications from 2000 to 2013 with the MeSH terms 'pericarditis',
      'myocarditis' and 'prognosis'. Additional publications were sought using the
      reference lists of identified papers, the published reviews on this topic, and a
      search of abstracts from the American Heart Association, American College of
      Cardiology, and European Society of Cardiology scientific sessions. RESULTS: We
      identified eight major clinical series evaluating the prognosis of
      myopericarditis. Studies included a total of 389 patients with myopericarditis
      (mean age 31.7 years, men-to-women ratio 4.0). After a mean follow-up of 31
      months, residual left-ventricular dysfunction was reported in 3.5% without cases
      of heart failure. Recurrences occurred in 13.0% of cases mainly as recurrent
      pericarditis (>90%), cardiac tamponade and constrictive pericarditis in less than
      1% of cases. The overall prognosis seems good (no mortality), with only one
      single discordant study reporting three deaths: one related to cardiac tamponade
      and two sudden cardiac deaths during hospitalization, but no out-of-hospital
      deaths during follow-up. CONCLUSION: Myopericarditis has a good overall
      prognosis. Troponin elevation in this setting does not predict an adverse outcome
      in most cases. Thus it is important to reassure the patients on their prognosis,
      explaining the nature of the disease and the likely course. Diagnostic and
      therapeutic choices should take into account the overall good outcome of these
      patients, including less invasive diagnostic tools and toxic drugs.

PMID- 24850500
TI  - Predicting the difficulty of a lead extraction procedure: the LED index.
AB  - BACKGROUND: According to recent surveys, many sites performing permanent lead
      extractions do not meet the minimum prerequisites concerning personnel training,
      procedures' volume, or facility requirements. The current Heart Rhythm Society
      consensus on lead extractions suggests that patients should be referred to more
      experienced sites when a better outcome could be achieved. The purpose of this
      study was to develop a score aimed at predicting the difficulty of a lead
      extraction procedure through the analysis of a high-volume center database. This
      score could help to discriminate patients who should be sent to a referral site.
      METHODS: A total of 889 permanent leads were extracted from 469 patients. All
      procedures were performed from January 2009 to May 2012 by two expert
      electrophysiologists, at the University Hospital of Brescia. Factors influencing
      the difficulty of a procedure were assessed using a univariate and a multivariate
      logistic regression model. The fluoroscopy time of the procedure was taken as an
      index of difficulty. A Lead Extraction Difficulty (LED) score was defined,
      considering the strongest predictors. RESULTS: Overall, 873 of 889 (98.2%) leads
      were completely removed. Major complications were reported in one patient (0.2%)
      who manifested cardiac tamponade. Minor complications occurred in six (1.3%)
      patients. No deaths occurred. Median fluoroscopic time was 8.7 min (3.3-17.3). A
      procedure was classified as difficult when fluoroscopy time was more than 31.2
      min [90th percentile (PCTL)].At a univariate analysis, the number of extracted
      leads and years from implant were significantly associated with an increased risk
      of fluoroscopy time above 90th PCTL [odds ratio (OR) 1.51, 95% confidence
      interval (CI) 1.08-2.11, P = 0.01; and OR 1.19, 95% CI 1.12-1.25, P < 0.001,
      respectively). After adjusting for patient age and sex, and combining with other
      covariates potentially influencing the extraction procedure, a multivariate
      analysis confirmed a 71% increased risk of fluoroscopy time above 90th PCTL for
      each additional lead extracted (OR 1.71, 95% CI 1.06-2.77, P = 0.028) and a 23%
      increased risk for each year of lead age (OR 1.23, 95% CI 1.15-1.31, P < 0.001).
      Further nonindependent factors increasing the risk were the presence of active
      fixation leads and dual-coil implantable cardiac defibrillator leads. Conversely,
      vegetations significantly favored lead extraction.The LED score was defined as:
      number of extracted leads within a procedure + lead age (years from implant) + 1
      if dual-coil - 1 if vegetation. The LED score independently predicted complex
      procedure (with fluoroscopic time >90th PCTL) both at univariate and multivariate
      analysis. A receiver-operating characteristic analysis showed an area under the
      curve of 0.81. A LED score greater than 10 could predict fluoroscopy time above
      90th PCTL with a sensitivity of 78.3% and a specificity of 76.7%. CONCLUSION: The
      LED score is easy to compute and potentially predicts fluoroscopy time above 90th
      PCTL with a relatively high accuracy.

PMID- 24850501
TI  - Role of the interfaces in multiple networked one-dimensional core-shell
      nanostructured gas sensors.
AB  - This study examined the gas sensing mechanism of multiple networked core-shell
      nanowire sensors. The ethanol gas sensing properties of In2O3/ZnO core-shell
      nanowires synthesized by the thermal evaporation of indium powder in an oxidizing
      atmosphere followed by the atomic layer deposition of ZnO were examined as an
      example. The pristine In2O3 nanowires and In2O3-core/ZnO-shell nanowires
      exhibited responses of ~30% and ~196%, respectively, to 1000 ppm ethanol at 300 
      degrees C. The response of the core-shell nanostructures to ethanol also showed a
      strong dependence on the shell layer width. The strongest response to ethanol was
      obtained with a shell layer thickness of ~44 nm corresponding to 2lambdaD, where
      lambdaD is the Debye length of ZnO. The enhanced sensing properties of the core
      shell nanowires toward ethanol can be explained based on the potential barrier
      controlled carrier transport model combined with the surface depletion model; the
      former is predominant over the latter. 

PMID- 24850502
TI  - Following a photoinduced reconstructive phase transformation and its influence on
      the crystal integrity: powder diffraction and theoretical study.
AB  - In the course of solid-state photoreactions, a single crystal (SC) of the
      reactant can be transformed into an SC of the product or it can lose
      crystallinity and become amorphous. In-between these two scenarios exist the
      reconstructive phase transformations, where upon irradiation, the reactant SC
      becomes a powder or an SC with increased mosaicity. We present a detailed
      description of reconstructive photodimerization, where the structural changes are
      directly correlated with the disintegration process. The kinetics of the reaction
      is explained by two kinetic regimes, forming an autocatalytic autoinhibition
      photoreaction set with high quantum yield. In addition, the photoreaction
      pathways were studied theoretically. 

PMID- 24850503
TI  - Stability of two resin combinations used as sealants against toothbrush abrasion
      and acid challenge in vitro.
AB  - OBJECTIVE: To test the stability of two conventional adhesives when combined with
      a low-viscosity caries infiltrant used for sealing sound enamel against
      toothbrush abrasion and acid challenge in vitro. MATERIALS AND METHODS: Bovine
      enamel discs (O = 3 mm) randomly assigned to three groups (n = 10/group) were
      etched with 37% phosphoric acid for 30 s and treated with resins of different
      monomer contents forming three test groups: (1) Untreated specimens (Control);
      (2) Infiltrant (Icon, DMG) + conventional enamel bonding adhesive (Heliobond,
      Ivoclar Vivadent); and (3) Infiltrant + conventional orthodontic adhesive
      (Transbond XT Primer, 3M Unitek). All specimens were immersed in hydrochloric
      acid (pH 2.6) for up to 9 days, during which they were exposed to 1825 toothbrush
      strokes per day. Calcium dissolution was assessed using Arsenazo III method at 24
      h intervals. Data were analyzed by Kruskal-Wallis and Wilcoxon signed ranks
      tests. RESULTS: Cumulative calcium dissolution for the untreated specimens (39.75
      +/- 7.32 MUmol/ml) exceeded the sealed groups (Icon + Heliobond: 23.44 +/- 7.03
      MUmol/ml; Icon + Transbond XT Primer: 22.17 +/- 5.34 MUmol/ml). Untreated
      specimens presented a relatively constant calcium dissolution rate throughout the
      experimental period, whereas the sealed groups presented a gradual increase
      indicating weakening of the seal by toothbrush abrasion. Both sealed groups
      presented significantly lower daily calcium dissolution at all time points
      compared to the control, except for Group 2 on the last measurement day.
      CONCLUSIONS: Low-viscosity caries infiltrant application on sound enamel prior to
      conventional resin application provided a protective effect against enamel
      demineralization, but this effect was not stable when challenged mechanically by
      toothbrush abrasion.

PMID- 24850504
TI  - Psychosocial well-being of prospective orthognathic-surgical patients.
AB  - OBJECTIVE: To compare the psychosocial well-being of prospective orthognathic
      surgical patients and controls. MATERIALS AND METHODS: Sixty patients referred
      for assessment of orthognathic-surgical treatment need and 29 controls
      participated. All participants filled in the modified version of Secord and
      Jourard's Body Image Questionnaire, the Orthognathic Quality of Life
      Questionnaire, the Rosenberg Self-Esteem scale, the Acceptance and Action
      Questionnaire II and a structured diary developed by the authors. Patients also
      filled in the Symptom Checklist 90. Patients assessed their dental appearance on
      a visual analogue scale modified from the Aesthetic Component (AC) of the Index
      of Orthodontic Treatment Need. Professional assessment was made from study models
      with the AC. RESULTS: Patients rating their dental appearance as AC grades 5-10
      suffered from lower orthognathic quality-of-life and poorer body image than the
      controls, while those with AC grades of 1-4 only had poorer oral function. Self
      perceived dental appearance was more important to orthognathic quality-of-life
      and body image than an orthodontist's assessment. Patients and controls had equal
      psychological flexibility and self-esteem. In all, 23-57% of patients had
      significant psychiatric symptoms, which explained the adverse emotions patients
      felt during the day. Fifteen per cent of the patients had been bullied.
      CONCLUSIONS: Many orthognathic-surgical patients cope well with their dentofacial
      deformities, despite functional masticatory problems. It seems that a subjective
      view of dental appearance may be a key factor in finding patients with
      psychosocial problems. It should be a major issue when considering psychosocial
      support and other treatment options.

PMID- 24850505
TI  - Is there a relationship between maternal periodontitis and pre-term birth? A
      prospective hospital-based case-control study.
AB  - OBJECTIVE: The aim of this study is to verify the existence of an association
      between maternal periodontal disease and pre-term delivery in an unselected
      population of post-partum Turkish women. MATERIALS AND METHODS: This case-control
      study was conducted on 100 women who gave birth in either a special or a
      government maternity hospital. The case group consisted of 50 mothers who had
      delivered an infant before 37 weeks' gestation and weighed under 2500 g. The
      control group included 50 mothers who had given birth to an infant with a birth
      weight of more than 2500 g and a gestational age of >=37 weeks. Data of mothers
      and infants were collected using medical registers and questionnaires. Clinical
      periodontal examinations were carried out in six sites on every tooth in the
      mother's mouth. A participant who presented at least four teeth with one or more
      sites with a PPD >=4 mm and CAL >=3 mm at the same site was considered to have
      periodontal disease. Statistical methods included parametric and non-parametric
      tests and multiple logistic regression analysis. RESULTS: There were no
      statistically significant differences between the cases and controls with regard
      to periodontal disease and pre-term delivery (OR = 1.48; 95% CI = 0.54-4.06).
      CONCLUSION: The findings indicated that maternal periodontitis was not a possible
      risk factor for pre-term delivery. Further studies with additional clinical
      trials are needed to explore the possible relationship between periodontal
      disease and pre-term birth.

PMID- 24850506
TI  - Determination of chemical components derived from 2% chlorhexidine gel
      degradation using gas chromatography-mass spectrometry.
AB  - OBJECTIVE: This study determined the chemical components derived from degradation
      of 2% chlorhexidine (CHX) gel and solution by using gas chromatography-mass
      spectrometry. MATERIALS AND METHODS: Three 2% CHX gels were used to identify the
      products of CHX gel degradation using gas chromatography-mass spectrometry. A
      solution of CHX was also evaluated to compare the degradation between gel and
      solution. Degradation was evaluated in four storage situations (on the worktable
      with light: on the worktable without light; in the Pasteur oven at 36.5 degrees C
      without light; and in the refrigerator at 8 degrees C without light).
      Measurements were made at four time points: initial analysis and 1, 3 and 6
      months after. The conversion of CHX into para-chloroaniline in storage situations
      and in different periods was analyzed statistically using chi-square test (alpha
      = 5%). RESULTS: The 2% CHX gel or solution had already degraded vial found within
      the period of validity, at all time points and for all storage conditions. The
      amount of para-chloroaniline (pCA) was directly proportional to time in the case
      of CHX solution, but not in CHX gel due to lack of homogeneity. CHX homogeneity
      in hydroxyethylcellulose gel was directly dependent on compounding mode.
      CONCLUSIONS: Degradation products, such as para-chloroaniline (pCA), orto-
      chloroaniline (oCA), meta-chloroaniline (mCA), reactive oxygen species (ROS) and
      organochlorines (ortho-chlorophenyl isocyanate and 2-amino-5-clorobenzonitrila)
      were found in 2% CHX gel and solution, regardless of storage conditions or time.
      In relationship to gel homogenization an alternative to produce 2% CHX gel and a
      new homogenization method have been developed.

PMID- 24850507
TI  - Influence of water sorption on mechanical properties of injection-molded
      thermoplastic denture base resins.
AB  - OBJECTIVE: This study investigated the influence of water sorption on certain
      mechanical properties of injection-molded thermoplastic denture base resins.
      MATERIALS AND METHODS: Six thermoplastic resins (two polyamides, two polyesters,
      one polycarbonate, one polymethylmethacrylate) and a polymethylmethacrylate
      (PMMA) conventional heat-polymerized denture-based polymer, selected as a
      control, were tested. Specimens of each denture base material were fabricated
      according to ISO 1567 specifications and were either dry or water-immersed for 30
      days (n = 10). The ultimate flexural strength, the flexural strength at the
      proportional limit and the elastic modulus of the denture base materials were
      calculated. RESULTS: Water sorption significantly decreased the ultimate flexural
      strength, the flexural strength at the proportional limit and the elastic modulus
      of one of the polyamides and the PMMAs. It also significantly increased the
      ultimate flexural strength of the polycarbonate. CONCLUSION: The mechanical
      properties of some injection-molded thermoplastic denture base resins changed
      after water sorption.

PMID- 24850508
TI  - Malignant transformation of oral lichen planus by a chronic inflammatory process.
      Use of topical corticosteroids to prevent this progression?
AB  - BACKGROUND: Oral lichen planus is a potentially malignant disorder with a
      capacity, although low, for malignant transformation. Of all the factors related
      to the process of malignant transformation, it is believed that the chronic
      inflammatory process plays a key role in the development of oral cancer. This
      inflammatory process is capable of providing a microenvironment based on
      different inflammatory cells and molecules that affect cellular growth,
      proliferation and differentiation. OBJECTIVES: The objectives of our study are:
      to review the available evidence about the possible relationship between the
      chronic inflammatory process present in oral lichen planus and its malignant
      transformation, to discuss the potential therapeutic implications derived from
      this relationship and to study the role that topical corticosteroids play in the
      control of oral lichen planus inflammation and its possible progression to
      malignant transformation. CONCLUSION: The maintenance of a minimum dose of
      topical corticosteroids could prevent the inflammatory progression of oral lichen
      planus to oral cancer.

PMID- 24850510
TI  - A chemoselective oxidation of monosubstituted ethylene glycol: facile synthesis
      of optically active alpha-hydroxy acids.
AB  - A mild and efficient method for the synthesis of optically active alpha-hydroxy
      acids through chemoselective oxidation of monosubstituted ethylene glycols using
      the TEMPO-NaOCl reagent system is described. It is evident from our studies that
      the solvent, pH and reaction temperature are very crucial for the success of this
      oxidation. The versatility of this method has been demonstrated with a variety of
      aliphatic, aromatic and carbohydrate substrates bearing various functional
      groups. 

PMID- 24850511
TI  - Efinaconazole (Jublia) for the treatment of onychomycosis.
AB  - Efinaconazole 10% nail solution (Jublia((r))) is a new topical triazole
      antifungal designed for the topical treatment of distal and lateral subungual
      onychomycosis. It inhibits ergosterol biosynthesis enzyme sterol 14alpha
      demethylase. Efinaconazole has lower minimum inhibitory concentrations than
      terbinafine, ciclopirox, itraconazole and amorolfine in Trichophyton rubrum,
      Trichophyton mentagrophytes and Candida albicans. The solution based formula has
      low surface tension and keratin binding properties that increase penetrance
      through the nail plate. Safety studies have shown that this formulation is not
      associated with atopic dermatitis or contact sensitivity. Duplicate Phase III
      clinical trials in adults with mild to moderate distal and lateral subungual
      onychomycosis indicate that efinaconazole 10% solution is an effective therapy
      with a pooled complete cure rate of 17% and a pooled mycological cure rate of
      54%. Efinaconazole 10% nail solution is a safe and effective new topical therapy
      for onychomycosis, which will fill a pressing need for more effective topical
      therapy in this disease. 

PMID- 24850512
TI  - [Migration].

PMID- 24850515
TI  - Present status of marijuana.

PMID- 24850517
TI  - Gynecologic examination.

PMID- 24850519
TI  - What a doctor should be.

PMID- 24850524
TI  - Cutting medicare hospital prices leads to a spillover reduction in hospital
      discharges for the nonelderly.
AB  - OBJECTIVE: To measure spillover effects of Medicare inpatient hospital prices on
      the nonelderly (under age 65). PRIMARY DATA SOURCES: Healthcare Cost and
      Utilization Project State Inpatient Databases (10 states, 1995-2009) and Medicare
      Hospital Cost Reports. STUDY DESIGN: Outcomes include nonelderly discharges,
      length of stay and case mix, staffed hospital bed-days, and the share of
      discharges and days provided to the elderly. We use metropolitan statistical
      areas as our markets. We use descriptive analyses comparing 1995 and 2009 and
      panel data fixed-effects regressions. We instrument for Medicare prices using
      accumulated changes in the Medicare payment formula. PRINCIPAL FINDINGS: Medicare
      price reductions are strongly associated with reductions in nonelderly discharges
      and hospital capacity. A 10-percent reduction in the Medicare price is estimated
      to reduce discharges among the nonelderly by about 5 percent. Changes in the
      Medicare price are not associated with changes in the share of inpatient hospital
      care provided to the elderly versus nonelderly. CONCLUSIONS: Medicare price
      reductions appear to broadly constrain hospital operations, with significant
      reductions in utilization among the nonelderly. The slow Medicare price growth
      under the Affordable Care Act may result in a spillover slowdown in hospital
      utilization and spending among the nonelderly.

PMID- 24850525
TI  - Classification and diagnosis of epileptic seizures.

PMID- 24850528
TI  - Frustrated Lewis pair modification by 1,1-carboboration: disclosure of a
      phosphine oxide triggered nitrogen monoxide addition to an intramolecular P/B
      frustrated Lewis pair.
AB  - The vicinal frustrated Lewis pair (FLP) mes2P-CH2CH2-B(C6F5)2 (3) reacts with
      phenyl(trimethylsilyl)acetylene by 1,1-carboboration to give the extended C3
      bridged FLP 6 featuring a substituted vinylborane subunit. The FLP 6 actively
      cleaves dihydrogen. The FLP 3 also undergoes a 1,1-carboboration reaction with
      diphenylphosphino(trimethylsilyl)acetylene to give the P/B/P FLP 11 that features
      a central unsaturated four-membered heterocyclic P/B FLP and a pendant CH2CH2
      Pmes2 functional group. Compound 11 reacts with nitric oxide (NO) by oxidation of
      the pendant Pmes2 unit to the P(O)mes2 phosphine oxide and N,N-addition of the
      P/B FLP unit to NO to yield the persistent P/B/PO FLPNO aminoxyl radical 14. This
      reaction is initiated by P(O)mes2 formation and opening of the central
      Ph2P...B(C6F5)2 linkage triggered by the pendant CH2CH2-P(O)mes2 group. 

PMID- 24850527
TI  - Patterns of pollen removal and deposition in Polemonium brandegeei
      (Polemoniaceae): the role of floral visitors, floral design and sexual
      interference.
AB  - The arrangement, colour, shape and size of floral parts (collectively floral
      design) have evolved primarily to promote mating success via animal-mediated
      pollen transfer. Although numerous studies have examined variation in pollinator
      assemblages, relatively few have examined patterns of pollen removal and
      deposition in the presence of fluctuating pollinators and ineffective floral
      visitors; therefore, net pollen removal and deposition by entire visitor
      assemblages are unclear. We studied the timing (diurnal or nocturnal) and effects
      of floral traits on pollen removal and deposition under a dynamic visitor
      assemblage of Polemonium brandegeei. We quantified pollen grains remaining in
      anthers (pollen removal) and deposited on stigmas (pollen deposition) of plants
      visited during either the day (07:30-20:00 h) or night (20:30-07:30 h) in natural
      populations over two flowering seasons. Pollen removal and deposition occurred
      both diurnally and nocturnally during our study. Increased diurnal removal and
      deposition coincided with peak floral visitations in 2006. This increase in
      pollen removal and deposition may reflect increased visits by pollen consumers,
      effective hawkmoth pollinators and increased self-pollen deposition due to hot,
      dry weather. Nonlinear effects of style length significantly affected pollen
      removal, with less pollen remaining in flowers with intermediate style lengths.
      Pollen deposition was more complex, with herkogamy and anther height affecting
      deposition. Further, close proximity of stigmas and anthers increased the
      potential for sexual interference between pollen removal and deposition. Overall,
      flower visitations and pollen removal and deposition varied between years and
      populations, but sex organ placement consistently influenced the removal and
      deposition of pollen. 

PMID- 24850529
TI  - Health-related quality of life and psychological well-being in patients with
      benign prostatic hyperplasia.
AB  - AIMS AND OBJECTIVES: To examine the health-related quality of life and
      psychological well-being of patients with benign prostatic hyperplasia and
      identify the predictive factors of health-related quality of life. BACKGROUND:
      Benign prostatic hyperplasia is highly prevalent in ageing men and causes
      bothersome lower urinary tract symptoms, which has a negative impact on their
      health-related quality of life. The current practice of managing benign prostatic
      hyperplasia focuses on relieving physical symptoms. However, the impact of benign
      prostatic hyperplasia on the patients' health-related quality of life and
      psychological well-being remains understudied, especially in the Asian
      population. DESIGN: A descriptive correlational survey study. METHODS: A
      convenience sample of 97 patients with benign prostatic hyperplasia was recruited
      at an outpatient urology clinic of a tertiary hospital in Singapore. The health
      related quality of life, lower urinary tract symptoms and psychological well
      being of the participants were assessed using the 12-item Short-Form Health
      Survey, International Prostate Symptom Score and the Hospital Anxiety and
      Depression Scale, respectively. RESULTS: The health-related quality of life
      scores were low with physical and mental health component scores of 47.0 and
      48.9, respectively, as assessed by the 12-item Short-Form Health Survey. There
      was a high prevalence of anxiety (10.3%) and depression (21.6%). Correlation
      analysis revealed significantly negative relationships between lower urinary
      tract symptoms, anxiety, depression and physical and mental health dimensions of
      the 12-item Short-Form Health Survey. Multiple linear regression analysis further
      identified that postvoid residual urine and lower urinary tract symptoms were
      predictive factors of the physical health dimension, whereas anxiety and
      depression were predictive factors of the mental health dimension of the 12-item
      Short-Form Health Survey. CONCLUSIONS: The health-related quality of life of
      patients with benign prostatic hyperplasia was poor, and their psychological well
      being was severely affected. Postvoid residual urine, lower urinary tract
      symptoms, anxiety and depression were identified to be significant predictive
      factors of the health-related quality of life of patients with benign prostatic
      hyperplasia. RELEVANCE TO CLINICAL PRACTICE: Findings from this study provide
      useful evidence-based information for healthcare professionals in the development
      and implementation of effective and culturally sensitive interventions to improve
      the health-related quality of life and psychological well-being of patients with
      benign prostatic hyperplasia.

PMID- 24850530
TI  - Epigenetic mechanisms in COPD: implications for pathogenesis and drug discovery.
AB  - INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is the fourth leading
      cause of death worldwide. The growing burden of COPD is due to continuous tobacco
      use, which is the most important risk factor of the disease, indoor fumes,
      occupational exposures and also aging of the world's population. Epigenetic
      mechanisms significantly contribute to COPD pathophysiology. AREAS COVERED: This
      review focuses on disease-relevant changes in DNA modification, histone
      modification and non-coding RNA expression in COPD, and provides insight into
      novel therapeutic approaches modulating epigenetic mechanisms. Recent findings
      revealed, among others, globally changed DNA methylation patterns, decreased
      levels of histone deacetylases and reduced microRNAs levels in COPD. The authors
      also discuss a potential role of the chromatin silencing Polycomb group of
      proteins in COPD. EXPERT OPINION: COPD is a highly complex disease and therapy
      development is complicated by the fact that many smokers develop both COPD and
      lung cancer. Of interest, combination therapies involving DNA methyltransferase
      inhibitors and anti-inflammatory drugs provide a promising approach, as they
      might be therapeutic for both COPD and cancer. Although the field of epigenetic
      research has virtually exploded over the last 10 years, particular efforts are
      required to enhance our knowledge of the COPD epigenome in order to successfully
      establish epigenetic-based therapies for this widespread disease.

PMID- 24850532
TI  - Risky decision making, prefrontal cortex, and mesocorticolimbic functional
      connectivity in methamphetamine dependence.
AB  - IMPORTANCE: Various neuropsychiatric disorders, especially addictions, feature
      impairments in risky decision making; clarifying the neural mechanisms underlying
      this problem can inform treatment. OBJECTIVE: To determine how methamphetamine
      dependent and control participants differ in brain activation during a risky
      decision-making task, resting-state functional connectivity within mesolimbic and
      executive control circuits, and the relationships between these measures. DESIGN,
      SETTING, AND PARTICIPANTS: A case-control, functional magnetic resonance imaging
      study of methamphetamine-dependent and healthy comparison participants at rest
      and when performing the Balloon Analogue Risk Task, which involves the choice to
      pump a balloon or to cash out in the context of uncertain risk. Conducted at a
      clinical research center at an academic institution, this study involved 25
      methamphetamine-dependent and 27 control participants. MAIN OUTCOMES AND
      MEASURES: Parametric modulation of activation in the striatum and right
      dorsolateral prefrontal cortex (rDLPFC; ie, the degree to which activation
      changed as a linear function of risk and potential reward), both indexed by pump
      number, and resting-state functional connectivity, measured in the whole brain
      with seeds in the midbrain and rDLPFC. Relationships between these outcomes were
      also tested. RESULTS: Parametric modulation of cortical and striatal activation
      by pump number during risk taking differed with group. It was stronger in the
      ventral striatum but weaker in the rDLPFC in methamphetamine-dependent
      participants than control individuals. Methamphetamine-dependent participants
      also exhibited greater resting-state functional connectivity of the midbrain with
      the putamen, amygdala, and hippocampus (P < .05, whole brain, cluster corrected).
      This connectivity was negatively related to modulation of rDLPFC activation by
      risk level during risky decision making. In control participants, parametric
      modulation of rDLPFC activation by risk during decision making was positively
      related to resting-state functional connectivity of the rDLPFC with the striatum.
      CONCLUSIONS AND RELEVANCE: Maladaptive decision making by methamphetamine users
      may reflect circuit-level dysfunction, underlying deficits in task-based
      activation. Heightened resting-state connectivity within the mesocorticolimbic
      system, coupled with reduced prefrontal cortical connectivity, may create a bias
      toward reward-driven behavior over cognitive control in methamphetamine users.
      Interventions to improve this balance may enhance treatments for stimulant
      dependence and other disorders that involve maladaptive decision making.

PMID- 24850535
TI  - Embryology of common urologic problems in children.

PMID- 24850533
TI  - Women's empowerment and child nutritional status in South Asia: a synthesis of
      the literature.
AB  - Women's disempowerment is hypothesised to contribute to high rates of
      undernutrition among South Asian children. However, evidence for this
      relationship has not been systematically reviewed. This review of empirical
      studies aims to: (1) synthesise the evidence linking women's empowerment and
      child nutritional status in South Asia and (2) suggest directions for future
      research. We systematically searched Global Health, Embase (classic and Ovid),
      MEDLINE, Campbell Collaboration, Popline, Eldis, Web of Science, EconLit and
      Scopus. We generated 1661 studies for abstract and title screening. We full-text
      screened 44 of these, plus 10 additional studies the authors were aware of. Only
      12 studies fulfilled our inclusion criteria. We included English materials
      published between 1990 and 2012 that examined the relationship(s) of at least one
      women's empowerment domain and nutritional status among South Asian children.
      Data were extracted and synthesised within three domains of empowerment: control
      of resources and autonomy, workload and time, and social support. The results
      showed women's empowerment to be generally associated with child anthropometry,
      but the findings are mixed. Inter-study differences in population
      characteristics, settings or methods/conceptualisations of women's empowerment,
      and the specific domains studied, likely contributed to these inconsistencies.
      This review also highlights that different women's empowerment domains may relate
      differently to child nutritional status. Future research should aim to harmonise
      definitions of women's empowerment, which key domains it should include, and how
      it is measured. Rigorous evaluation work is also needed to establish which
      policies and programmes facilitate women's empowerment and in turn, foster child
      nutritional well-being. 

PMID- 24850536
TI  - Intranasal H5N1 vaccines, adjuvanted with chitosan derivatives, protect ferrets
      against highly pathogenic influenza intranasal and intratracheal challenge.
AB  - We investigated the protective efficacy of two intranasal chitosan (CSN and TM
      CSN) adjuvanted H5N1 Influenza vaccines against highly pathogenic avian Influenza
      (HPAI) intratracheal and intranasal challenge in a ferret model. Six groups of 6
      ferrets were intranasally vaccinated twice, 21 days apart, with either placebo,
      antigen alone, CSN adjuvanted antigen, or TM-CSN adjuvanted antigen. Homologous
      and intra-subtypic antibody cross-reacting responses were assessed. Ferrets were
      inoculated intratracheally (all treatments) or intranasally (CSN adjuvanted and
      placebo treatments only) with clade 1 HPAI A/Vietnam/1194/2004 (H5N1) virus 28
      days after the second vaccination and subsequently monitored for morbidity and
      mortality outcomes. Clinical signs were assessed and nasal as well as throat
      swabs were taken daily for virology. Samples of lung tissue, nasal turbinates,
      brain, and olfactory bulb were analysed for the presence of virus and examined
      for histolopathological findings. In contrast to animals vaccinated with antigen
      alone, the CSN and TM-CSN adjuvanted vaccines induced high levels of antibodies,
      protected ferrets from death, reduced viral replication and abrogated disease
      after intratracheal challenge, and in the case of CSN after intranasal challenge.
      In particular, the TM-CSN adjuvanted vaccine was highly effective at eliciting
      protective immunity from intratracheal challenge; serologically, protective
      titres were demonstrable after one vaccination. The 2-dose schedule with TM-CSN
      vaccine also induced cross-reactive antibodies to clade 2.1 and 2.2 H5N1 viruses.
      Furthermore ferrets immunised with TM-CSN had no detectable virus in the
      respiratory tract or brain, whereas there were signs of virus in the throat and
      lungs, albeit at significantly reduced levels, in CSN vaccinated animals. This
      study demonstrated for the first time that CSN and in particular TM-CSN
      adjuvanted intranasal vaccines have the potential to protect against significant
      mortality and morbidity arising from infection with HPAI H5N1 virus.

PMID- 24850537
TI  - Verification of a new biocompatible single-use film formulation with optimized
      additive content for multiple bioprocess applications.
AB  - Single-use bioprocessing bags and bioreactors gained significant importance in
      the industry as they offer a number of advantages over traditional stainless
      steel solutions. However, there is continued concern that the plastic materials
      might release potentially toxic substances negatively impacting cell growth and
      product titers, or even compromise drug safety when using single-use bags for
      intermediate or drug substance storage. In this study, we have focused on the in
      vitro detection of potentially cytotoxic leachables originating from the recently
      developed new polyethylene (PE) multilayer film called S80. This new film was
      developed to guarantee biocompatibility for multiple bioprocess applications, for
      example, storage of process fluids, mixing, and cell culture bioreactors. For
      this purpose, we examined a protein-free cell culture medium that had been used
      to extract leachables from freshly gamma-irradiated sample bags in a standardized
      cell culture assay. We investigated sample bags from films generated to establish
      the operating ranges of the film extrusion process. Further, we studied sample
      bags of different age after gamma-irradiation and finally, we performed extended
      media extraction trials at cold room conditions using sample bags. In contrast to
      a nonoptimized film formulation, our data demonstrate no cytotoxic effect of the
      S80 polymer film formulation under any of the investigated conditions. The S80
      film formulation is based on an optimized PE polymer composition and additive
      package. Full traceability alongside specifications and controls of all critical
      raw materials, and process controls of the manufacturing process, that is, film
      extrusion and gamma-irradiation, have been established to ensure lot-to-lot
      consistency.

PMID- 24850538
TI  - The critical role of peritoneal cytology in the staging of gastric cancer: an
      evidence-based review.
AB  - Positive peritoneal cytology (Cyt+) is an important staging tool for patients
      with locally advanced gastric cancer. The objective of this review is to evaluate
      the current literature regarding cytology evaluation in patients with gastric
      cancer and to provide recommendations on the inclusion of this powerful
      prognosticator in patients with this disease. A literature search was performed
      for recent and pertinent studies evaluating peritoneal cytology in patients with
      gastric adenocarcinoma. Peritoneal cytology as the only evidence for M1 disease
      is present in up to 10% of patients with locally advanced gastric cancer;
      survival in the setting of Cyt+ is dismal when gastrectomy is the first line of
      therapy. Improved survival is associated with response to chemotherapy indicated
      by conversion to negative cytology, good performance status, and antral tumors.
      Highly select patients with Cyt+ treated with gastrectomy show improved survival
      in only some of the available studies. There are high quality studies that
      support the routine practice of peritoneal cytology evaluation in patients with
      locally advanced gastric cancer. The role of gastrectomy remains unclear in
      patients with Cyt+ and clinical trials are needed to define the best treatment
      option for this select group of patients.

PMID- 24850539
TI  - Acute care for frail older people: time to get back to basics?

PMID- 24850540
TI  - Effects of functional tasks exercise on older adults with cognitive impairment at
      risk of Alzheimer's disease: a randomised controlled trial.
AB  - OBJECTIVE: the aim of this study was to compare the effects of a functional tasks
      exercise programme to a cognitive training programme in older adults with mild
      cognitive impairment. DESIGN: a single-blind randomised control trial with the
      intervention group compared with an active control group. SETTING: out-patient
      clinic. PARTICIPANTS: older adults with mild cognitive impairment (n = 83) aged
      60 and older living in the community. METHODS: participants were randomised to
      either a functional task exercise group (n = 43) or an active cognitive training
      group (n = 40) for 10 weeks. All outcome measures were undertaken at baseline,
      post-intervention and 6-month follow-up using Neurobehavioral Cognitive Status
      Examination, Trail Making Test, Chinese Version Verbal Learning Test, Category
      Verbal Learning Test, Lawton Instrumental Activities of Daily Living Scale and
      Problems in Everyday Living Test. RESULTS: the functional task exercise group
      showed significant between-group differences in general cognitive functions,
      memory, executive function, functional status and everyday problem solving
      ability. The improvements were sustained over time at 6-month follow-up.
      CONCLUSION: a functional tasks exercise programme is feasible for improving
      cognitive functions and functional status of older adults with mild cognitive
      impairment. This may serve as a cost-effective adjunct to the existing
      interventions for populations with mild cognitive impairment. TRIAL REGISTRATION
      NUMBER: ACTRN12610001025022.

PMID- 24850541
TI  - National audit of continence care: adherence to National Institute for Health and
      Clinical Excellence (NICE) guidance in older versus younger adults with faecal
      incontinence.
AB  - BACKGROUND: previous UK National Audits of Continence Care showed low rates of
      assessment and treatment of faecal incontinence (FI) in older people. OBJECTIVE:
      the 2009 audit assessed adherence to the National Institute for Health and
      Clinical Excellence guidelines on management of FI and compared care in older
      versus younger patients. METHODS: fifteen older (65+) and 15 younger (18-65)
      patients with FI were to be audited in hospital (inpatient or outpatient),
      primary care (PC) and care home sites. RESULTS: data were submitted for n = 2,930
      cases from 133 hospitals, n = 1,729 from 97 PC surgeries and n = 693 from 63 care
      homes. Bowel history was not documented in 41% older versus 24% younger patients
      in hospitals and 27 versus 19% in PC (both P < 0.001). In older people, there was
      no documented focused examination in one-third in hospitals, one-half in PC and
      three-quarters in care homes. Overall, <50% had documented treatment for an
      identified bowel-related cause of FI. FI was frequently attributed to co
      morbidity. Few patients received copies of their treatment plan. Quality-of-life
      impact was poorly documented particularly in hospitals. CONCLUSIONS: this
      national audit shows deficits in documented assessment, diagnosis and treatment
      for adults with FI despite availability of clinical guidance. Overall care is
      significantly poorer for older people. Clinicians, including geriatricians, need
      to lead on improving care in older people including comprehensive assessment
      where needed. Improvement in some indicators in older people with successive
      audits suggests that ongoing national audit with linked information resources can
      be useful as both monitor and agent for change.

PMID- 24850542
TI  - Functional decline of older patients 1 year after cardiothoracic surgery followed
      by intensive care admission: a prospective longitudinal cohort study.
AB  - BACKGROUND: there is a growing demand for cardiothoracic surgery in patients'
      aged >=65 years. OBJECTIVE: : to explore which variables were independently
      associated with functional decline 12 months after cardiothoracic surgery
      followed by intensive care admission. DESIGN: prospective cohort study. SETTING:
      cardiothoracic unit of a university teaching hospital. SUBJECTS: a total of 356
      elderly patients undergoing cardiothoracic surgery followed by intensive care
      unit admission. METHODS: functioning was assessed at hospital admission and 3 and
      12 months after hospital discharge with the modified Katz activities of daily
      living (ADL) index. Data collection included demographics, surgical procedure,
      diagnosis, comorbidities, pre-morbid geriatric conditions and intensive care unit
      length of stay. Functional decline was defined as a one-point loss on the
      modified Katz ADL index score at 1 year compared with baseline functioning at
      hospital admission. Logistic regression analysis was performed to study the
      association between independent variables and functional decline. RESULTS: the 1
      year mortality rate was 8.7% of which 4.8% was in-hospital mortality. The
      youngest group consisted of 295 patients (64% men; 72 +/- 4 years), there were 61
      octogenarians (56% men; 82 +/- 2 years). One year after hospital discharge,
      younger patients demonstrated less functional decline (45 versus 56%, P < 0.001).
      Cognitive impairment, higher age, female gender, alcohol use, type of cardiac
      procedure and serum creatinine were independently associated with functional
      decline 1 year after discharge. CONCLUSIONS: the survival rates after
      cardiothoracic surgery were good, the rates of functional decline were
      substantial. These results suggest that studies on geriatric rehabilitation
      before and after surgery might be needed to overcome the decline in functioning.

PMID- 24850543
TI  - Mean platelet volume in patients with non-alcoholic fatty liver disease: is mean
      platelet volume ready as a surrogate marker?

PMID- 24850544
TI  - Modification of abdominal fat distribution after aromatase inhibitor therapy in
      breast cancer patients visualized using 3-D computed tomography volumetry.
AB  - INTRODUCTION/BACKGROUND: The purpose of this study was to describe modification
      of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT)
      distributions in breast cancer patients after aromatase inhibitor (AI) therapy
      using computed tomography (CT) volumetric measurement of abdominal body fat
      distribution. PATIENTS AND METHODS: Sixty-four consecutive patients who were
      receiving adjuvant AI therapy were included in this study. Patients were
      evaluated using CT before and after at least 6 months of AI therapy with imaging
      follow-up of 4.3 +/- 2.2 years. Abdominal fat distribution was automatically
      calculated using a workstation that obtained total abdominal adipose tissue
      (TAAT) area (mm(3)). SAT was manually segmented and VAT was determined as TAAT -
      SAT. Percentages were calculated for change of TAAT, VAT, and SAT. VAT/SAT ratio
      was calculated. RESULTS: Percentage of TAAT after AI therapy was increased by a
      mean of 9.1% from baseline (16,280.3 +/- 6953.3 mm(3)) to (17,763.6 +/- 6850.8
      mm(3)). Two groups of patients were observed; those with an increase in TAAT and
      those with a decrease. Modification of VAT/SAT ratio was observed (from 1.38 to
      1.69) in all subjects, reflecting a relative increased volume of VAT (mean, 18%)
      and slight mean reduction of SAT (mean 1.9%). CONCLUSION: In our study, therapy
      with AI in breast cancer patients was accompanied with a change in fat
      distribution to relatively greater VAT/SAT ratio in patients, regardless of
      whether they gained or lost weight after therapy. Because this pattern of fat
      distribution is associated with metabolic disorders, attention must be paid to
      these clinical manifestations in patients during their follow-up management.

PMID- 24850545
TI  - Hot and cold: coexistent Graves' disease and Hashimoto's thyroiditis in a patient
      with Schmidt's syndrome.
AB  - A 37-year-old housewife presented with generalised fatigue, palpitations and
      weight loss over the past 3 months. Physical examination revealed signs of
      hyperthyroidism. Thyroid function tests confirmed the presence of thyrotoxicosis.
      Pertechnetate radionuclide imaging of the thyroid showed diffusely increased
      radiotracer uptake consistent with Graves' disease and a cold nodule in the right
      lobe. Needle aspiration from the nodule yielded evidence of Hashimoto's
      thyroiditis. The patient also tested strongly positive for antithyroid peroxidase
      antibodies. Simultaneous laboratory evaluation revealed primary adrenal failure
      and probable pernicious anaemia, thus producing a diagnosis of Schmidt's
      syndrome. The patient was initiated on appropriate medical therapy for
      endocrinopathy. Graves' disease was treated with radioablation.

PMID- 24850546
TI  - Against all odds. Conservative management of Boerhaave's syndrome.
AB  - Spontaneous oesophageal perforation or Boerhaave's syndrome is a life-threatening
      condition that usually requires early diagnosis and early surgical management. A
      79-year-old man presented to the accident and emergency department with an
      ischaemic left big toe. He reported a 2-week history of worsening symptoms and a
      claudication distance in his left leg of 20-30 m. Three days post
      revascularisation of the leg, the patient reported chest pain radiating to the
      back. CT angiography of the aorta indicated Boerhaave's syndrome. Following 35
      days of conservative management in the intensive care unit and high dependency
      unit, the patient was stepped down to a surgical ward. A water-soluble contrast
      study demonstrated minimal leak through the perforated oesophagus. The patient
      was started on oral intake, which was well tolerated. This case highlights that
      conservative management may be appropriate. 

PMID- 24850547
TI  - The development of pulmonary aspergillosis and pneumothorax in a patient with
      neutropenic systemic lupus erythematosus and successful treatment of the first
      case.
AB  - There are reports on patients with systemic lupus erythematosus (SLE) with
      aspergillosis; however, aspergillosis-related pneumothorax has not been reported
      in SLE. We present a female patient with active SLE who was administered high
      dose steroids, developed an opportunistic bacterial infection and had a cavitary
      pulmonary lesion. Sputum cultures yielded Aspergillus fumigatus. She was
      administered voriconazole. She developed dyspnoea and chest X-ray showed
      pneumothorax. She was placed with an underwater drainage chest tube; the
      pneumothorax and the pulmonary lesion regressed. 

PMID- 24850548
TI  - Improving patient outcomes in hereditary angioedema: reducing attack frequency
      using routine prevention with C1 inhibitor concentrate.
AB  - Hereditary angioedema (HAE) is a rare inherited disorder, characterised by
      recurrent oedema attacks in various regions of the body. In HAE, mutations in the
      C1 esterase inhibitor (C1-INH) gene result in decreased C1-INH concentrations
      (type I HAE) or functionally deficient C1-INH (type II HAE), leading to
      inappropriate activation of the kallikrein-kinin system and release of vasoactive
      mediators. Treatment of HAE aims to manage acute attacks (using replacement C1
      INH or bradykinin B2 receptor antagonist) or prevent attacks through prophylaxis
      (using C1-INH or attenuated androgens). We present a case of a 67-year-old man
      with HAE who suffered a high number of breakthrough HAE attacks while undergoing
      long-term prophylaxis with attenuated androgens. Androgen therapy was safely
      discontinued and routine prevention therapy with C1-INH (1000 U) introduced as
      part of an individualised management approach, in line with published clinical
      trial data, which improved patient outcomes in terms of HAE attack frequency and
      severity. 

PMID- 24850549
TI  - Post occlusive left atrial appendage thrombosis with extension into the left
      atrium.
AB  - A 67-year-old man underwent left atrial appendage (LAA) exclusion concomitant
      with mitral valve surgery and radiofrequency ablation maze procedure. On
      transoesophageal echocardiography anticipating ablation for left atrial
      tachycardia, an echodense thrombus was visualised in the LAA location with
      apparent intracavitary extension into the left atrium. Based on CT imaging
      findings, the echo represented thrombosis of a large left atrial appendage with
      probable extension into the left atrium. 

PMID- 24850550
TI  - Recurrent cardiac tamponade: an initial presentation of lung adenocarcinoma.
AB  - A 63-year-old hypertensive woman presented initially to the surgical team with
      right upper quadrant pain, the patient was otherwise asymptomatic and clinically
      well. An abdominal CT scan excluded any surgical diagnoses but rather showed a
      pericardial effusion. When the cardiology team urgently reviewed her, they found
      her to be hypotensive and tachycardic with a raised jugular venous pressure. A
      diagnosis of cardiac tamponade was made and was transferred to the coronary care
      unit for an emergency pericardiocentesis. She developed tamponade on further
      occasions requiring pericardiocentesis. The underlying cause was investigated and
      following pericardial fluid analysis and subsequent imaging, metastatic lung
      adenocarcinoma was diagnosed. 

PMID- 24850551
TI  - Surgical management of pheochromocytoma in a 13-week pregnant woman.
AB  - A 34-year-old 13-week pregnant woman presented with hypertension refractory to
      medical therapy and on workup was found to have a right adrenal mass. Due to her
      persistent increased blood pressure she was advised urinary vanillylmandelic acid
      (VMA) and its level was raised. MRI of the abdomen showed a well-circumcised
      lesion in the right adrenal of 3.0*2.5 cm suggestive of pheochromocytoma. The
      patient was started on antihypertensives including alpha-blockers and beta
      blockers and planned for right open adrenalectomy. Intraoperatively, blood
      pressure was raised up to 180/110 mm Hg on slight manipulation of adrenal gland
      which was controlled with glyceryl-trinitrate and volatile agents.
      Postoperatively urinary VMA decreased to normal range and all antihypertensives
      were gradually stopped. She had uneventful pregnancy and delivered vaginally.
      This case report highlights the importance of surgical management of
      pheochromocytoma in second trimester of pregnancy to avoid catastrophic
      complications later in pregnancy.

PMID- 24850552
TI  - Persistent left superior vena cava in association with sinus venosus defect type
      of atrial septal defect and partial pulmonary venous return on 64-MDCT.
AB  - The most common venous abnormality of the thorax is persistent left superior vena
      cava (PLSVC), incidence being less than 0.5%. However, with congenital heart
      disease, it is about 6.1%. When the coronary sinus is dilated always search for
      PLSVC. The coronary sinus may communicate with the left atrium. This is known as
      an unroofed coronary sinus (UCS) and preoperatively documenting it is important.
      Of all the congenital cardiac anomalies, the sinus venosus defect (SVD) type of
      atrial septal defect (ASD) is most commonly associated with PLSVC and accounts
      for 4-11% of all ASDs. Multidetector CT can easily show all these abnormalities
      along with haemodynamics. On transoesophageal echocardiography it is difficult to
      characterise SVD and visualise a coronary sinus because of a limited window,
      contrast resolution and poor patient compliance. The complex of UCS and PLSVC is
      one such abnormality and its treatment requires careful assessment of other
      concomitant cardiac abnormalities to prevent post-treatment haemodynamic
      complications.

PMID- 24850553
TI  - Acute Marchiafava-Bignami disease: clinical and serial MRI correlation.
AB  - Marchiafava-Bignami disease (MBD) is a form of toxic demyelinating disease more
      often seen in chronic alcoholics. The disease process typically involves the
      corpus callosum and clinically often presents with altered sensorium,
      neurocognitive defects or seizures with acute cases often deteriorating to
      comatose state. The death rate is high. We report a rare case of MBD with
      complete clinical recovery. A 50-year-old male patient presented in an
      unconscious state and underwent MRI of the brain which showed significant lesions
      involving the corpus callosum. Following treatment with thiamine and supportive
      therapy, he improved clinically and a follow-up MRI revealed significant
      resolution of the earlier lesions. Diffusion-weighted MRI showed the changes more
      conspicuously as compared with conventional imaging. The clinical resolution
      corresponded well with the MRI pattern. The case highlights that diffusion
      weighted MRI is an extremely useful tool in evaluation and prognostication of
      MBD. 

PMID- 24850554
TI  - One lump or two? Concomitant Leydig cell tumour and paratesticular leiomyoma in
      an adult man.
AB  - We present the first reported case of a concomitant Leydig cell tumour (LCT) and
      paratesticular leiomyoma in an adult man with a history of bilateral
      cryptorchidism. An 80-year-old man presented with a 2-month history of a left
      testicular lump associated with mild discomfort and a gradual increase in size on
      a background of bilateral cryptorchidism requiring multiple orchidopexy
      procedures as a child. Ultrasound confirmed a lesion suspicious for malignancy
      and he proceeded to a left radical orchidectomy. Histopathological assessment of
      the left testis revealed a concomitant testicular LCT with rare malignant
      features and paratesticular leiomyoma. 

PMID- 24850555
TI  - Sympathetic ophthalmitis with predominant posterior segment involvement.
AB  - We report a case of a 22-year-old obese man, intellectually disabled since birth,
      who developed sympathetic ophthalmitis in his right eye (RE) 2 months after a
      penetrating injury to his left eye; this despite primary repair went into
      phthisis with no perception of light. Initially the patient presented with
      features of anterior uveitis in the RE, for which oral and topical steroids were
      prescribed. The patient failed to keep regular follow-up appointments, and
      returned 2 months later with exudative retinal detachment, and was placed on
      steroids and immunosuppressives. The visual acuity of the RE on discharge was
      6/60 with -0.5*180.

PMID- 24850556
TI  - Salt-losing nephropathy in hypothyroidism.
AB  - A 35-year-old man presented with recurrent lower extremity weakness associated
      with polyuria later progressing to generalised weakness with difficulty in
      breathing. The patient was hypotensive and dry, with normal thyroid and chest
      examination, weak lower extremity and carpopedal spasm. Workup revealed
      hypokalaemia, hyponatraemia, hypocalcaemia, hypomagnesaemia, hypochloraemia and
      hypophosphataemia. Arterial blood gas showed respiratory alkalosis with good
      oxygenation. Twenty-four-hour urine collection showed normal volume with
      electrolyte wasting. Thyroid function test revealed overt hypothyroidism with
      negative antithyroid peroxidase. The patient was well after treatment with
      levothyroxine, volume and electrolyte replacement and was discharged. Thyroid
      hormones are related to the expression of the Na-K-ATPase, Na-Pi cotransporter,
      Mg-ATPase and Na-Ca exchanger pumps in the renal tubules. Sodium, potassium,
      phosphate, calcium, magnesium and water losses result from decreased expression
      of these pumps. 

PMID- 24850557
TI  - Managing advanced unilateral pseudoexfoliative glaucoma.
AB  - The only proven therapy for glaucoma is intraocular pressure (IOP) reduction,
      which can be accomplished by different means. Each should be properly discussed
      with patients in order to best preserve visual function and quality of life. We
      report a case of unilateral pseudoexfoliative glaucoma, treated for years with
      triple topical IOP-lowering drugs. The patient presented with advanced optic
      neuropathy and important ocular side effects secondary to the treatment. Having
      discussed his options and prognosis, laser trabeculoplasty was performed while
      maintaining the remaining therapy considering the advanced stage of glaucoma. His
      IOP was effectively reduced and no progression was noted after 1-year follow-up.
      Although medical therapy is the mainstream in glaucoma management, its side
      effects should not be ignored, especially in unilateral cases. Surgery might have
      been a better solution, but we chose to perform laser trabeculoplasty, an
      effective and safer alternative, considering the unlikely but serious risk of the
      "wipe-out phenomenon" in this case. 

PMID- 24850558
TI  - Suspected hydatid cyst of liver harbouring an aggressive desmoplastic small round
      cell tumour.
AB  - Among the group of small round cell tumours, there is a distinct and rare tumour
      known as desmoplastic small round cell tumour (DSRCT). DSRCT presents as
      multiple, widespread masses in the abdomen and pelvis and may be accompanied by
      extensive tumour implants throughout the peritoneum as the tumour is known to
      spread diffusely along serosal surfaces. We discuss a case of DSRCT in a 16-year
      old boy who presented with abdominal pain since 2 years, a non-tender mass was
      palpable on the right upper quadrant of the abdomen, ultrasonographic and CT
      findings suggested hydatid cyst of liver. Laparotomy revealed multiple small
      peritoneal deposits along with a single mass in the liver. On histopathology, the
      lesion was found to be neoplastic and composed of predominantly clusters of small
      round blue cells, in a desmoplastic stroma; tumour cells were diffusely positive
      for cytokeratin, vimentin and neuron-specific enolase, thus confirming the
      diagnosis of DSRCT. 

PMID- 24850559
TI  - False-positive tuberculous meningitis due to laboratory contamination: importance
      of a holistic clinical evaluation.
AB  - Incidence of tuberculosis in Nebraska is 1.9/100,000 people. Tuberculous
      meningitis is rare and comprises 1% of extrapulmonary tuberculosis. An elderly
      Caucasian man presented with fever, headache, altered mentation and a history of
      tick bite. Cerebrospinal fluid (CSF) analysis showed negative cultures and the
      patient was treated empirically for tickborne illness. Forty-five days later, CSF
      nucleic acid amplification test (NAAT) was positive for tuberculosis. On
      readmission, repeat neurological examination and CSF analysis were benign and the
      patient was not offered antituberculous treatment. Genotype investigation of the
      culture and NAAT specimen by the Center for Disease Control confirmed laboratory
      contamination. The literature reports an incidence of 2-4% for false-positive
      tuberculosis cultures. Contaminated devices, clerical errors and laboratory
      errors have been implicated. Laboratory contamination results in smear-negative
      culture-positive cases. Epidemiological investigation with genotype testing is
      confirmatory. Detailed clinical assessment with good clinical and laboratory
      communication and frequent laboratory surveillance is advocated to mitigate these
      cases.

PMID- 24850560
TI  - Beware the person with the glass eye and the large liver.

PMID- 24850561
TI  - Face the truth: a 76-year-old man with chronic heart failure of unknown origin.

PMID- 24850562
TI  - Huge right atrial thrombus after discontinuation of anticoagulant therapy in
      atrial fibrillation.

PMID- 24850564
TI  - A pediatrician's view.

PMID- 24850565
TI  - Accelerated water quality improvement during oligotrophication in peri-alpine
      lakes.
AB  - Monitoring of four eutrophic Swiss lakes undergoing oligotrophication during more
      than 25 years (i.e., gradually decreasing nutrient loading, productivity, and
      associated symptoms of eutrophication) revealed that phosphorus (P) net
      sedimentation rates (the fraction of a lake's total P content that is buried
      within its sediments each year) and P export rates (the fraction of the lakes'
      total P content that is exported via the outlet each year) increased as the
      lakes' P contents decreased. These findings are of scientific as well as
      practical interest because they imply that, contrary to the hitherto prevailing
      view, the P concentration of eutrophic lakes will decrease more than proportional
      to the reduction of their external P load, and faster than predicted by the
      linear (eutrophic state-based) models. 

PMID- 24850567
TI  - Can obesity be prevented?

PMID- 24850566
TI  - Direct observation of ionic structure at solid-liquid interfaces: a deep look
      into the Stern Layer.
AB  - The distribution of ions and charge at solid-water interfaces plays an essential
      role in a wide range of processes in biology, geology and technology. While
      theoretical models of the solid-electrolyte interface date back to the early 20th
      century, a detailed picture of the structure of the electric double layer has
      remained elusive, largely because of experimental techniques have not allowed
      direct observation of the behaviour of ions, i.e. with subnanometer resolution.
      We have made use of recent advances in high-resolution Atomic Force Microscopy to
      reveal, with atomic level precision, the ordered adsorption of the mono- and
      divalent ions that are common in natural environments to heterogeneous
      gibbsite/silica surfaces in contact with aqueous electrolytes. Complemented by
      density functional theory, our experiments produce a detailed picture of the
      formation of surface phases by templated adsorption of cations, anions and water,
      stabilized by hydrogen bonding.

PMID- 24850568
TI  - Temperature-induced attractive interactions of PEO-containing block copolymer
      micelles.
AB  - Interactions in a temperature sensitive-colloidal model system are investigated
      over a wide range of temperatures and concentrations to characterize the
      interparticle interactions within the system. This model system is composed of
      poly(ethylene oxide) end-capped with an octadecyl chain (C18E100), which by small
      angle X-ray scattering (SAXS) have been shown to form spherical micelles in an
      aqueous salt solution. In the present study a 0.9 M NaF solution is used to shift
      the cloud point into the experimentally convenient temperature range.
      Densitometry and SAXS have shown no indication of specific interactions between
      the salt ions and the micelles. The spherical micelles are found to persist at
      elevated temperatures and a change in interparticle interaction is observed by
      viscometry and SAXS. The results are all consistent with the decreased solvent
      quality of water toward poly(ethylene oxide) with increasing temperature and it
      is seen that attractive interparticle interactions emerge in the vicinity of the
      cloud point. 

PMID- 24850569
TI  - Two novel mutations in the C-terminal region of centrosomal protein 290 (CEP290)
      result in classic Joubert syndrome.
AB  - Joubert syndrome is a neurologic disorder with a pathognomonic "molar tooth sign"
      on brain imaging. The purpose of this study was to identify potential mutations
      in a Chinese patient with Joubert syndrome by targeted massively parallel
      sequencing. Taking advantage of high-throughput DNA sequencing technologies, 18
      Joubert-causing genes of a Chinese patient with classic Joubert syndrome were
      sequenced at a time, and 2 novel variants in the CEP290 gene (c.7323_7327delAGAAG
      and c.6012-2A>G) were identified in this patient. Sanger validation showed that 2
      variants were inherited from each parents, respectively. Both variants are
      located in the C-terminal region of the CEP290 protein and are predicted to be
      deleterious. The results support that the combination of targeted genes
      enrichment and next-generation sequencing is valuable molecular diagnostic tool
      and suitable for clinical application. 

PMID- 24850570
TI  - Ornithine transcarbamylase deficiency presenting with acute reversible cortical
      blindness.
AB  - Acute focal neurologic deficits are a rare but known presentation of ornithine
      transcarbamylase deficiency, particularly in females. We describe here a 6-year
      old girl with newly diagnosed ornithine transcarbamylase deficiency who presents
      with an episode of acute cortical blindness lasting for 72 hours in the absence
      of hyperammonemia. Her symptoms were associated with a subcortical low-intensity
      lesion with overlying cortical hyperintensity on fluid-attenuated inversion
      recovery magnetic resonance imaging (MRI) of the occipital lobes. Acute
      reversible vision loss with these MRI findings is an unusual finding in patients
      with ornithine transcarbamylase deficiency. Our findings suggest a role for
      oxidative stress and aberrant glutamine metabolism in the acute clinical features
      of ornithine transcarbamylase deficiency even in the absence of hyperammonemia. 

PMID- 24850571
TI  - Transient restricted diffusion of corpus callosum and subcortical white matter
      following febrile status epilepticus.
AB  - We describe the case of a 41/2-year-old girl with prolonged febrile status
      followed by abnormal behavior and loss of speech. Interesting findings on
      diffusion-restricted imaging were noted. The clinicoradiologic possibilities are
      discussed. 

PMID- 24850572
TI  - International Classification of Functioning, Disability and Health (ICF) as a
      framework for change: revolutionizing rehabilitation.
AB  - The International Classification of Functioning, Disability and Health (ICF)
      utilizes domains of body functions and structures, activities and participation,
      as well as environmental and personal factors to fully encapsulate the concepts
      of health and disability. The International Classification of Functioning,
      Disability and Health provides a rich and holistic understanding of functioning
      that is particularly valuable in the setting of childhood disability and
      rehabilitation. With applicability that enhances a nuanced understanding of each
      child within their family, school, and community, the International
      Classification of Functioning, Disability and Health also ensures facile and
      meaningful communication between professionals. Use of the International
      Classification of Functioning, Disability and Health promotes improved treatment
      plans for individual children and for larger programmatic decisions. This article
      demonstrates how the International Classification of Functioning, Disability and
      Health has reinvented the language and understanding of childhood disability and
      rehabilitation. 

PMID- 24850573
TI  - Radiologic approach to the diagnosis of pulmonary disorders in premature infants.

PMID- 24850574
TI  - WHO reforms: on course but core functions still require reliable support.

PMID- 24850578
TI  - Clinical studies in behavior therapy with children, adolescents and their
      families.

PMID- 24850577
TI  - Vervet MRI atlas and label map for fully automated morphometric analyses.
AB  - Currently available non-human primate templates typically require input of a
      skull-stripped brain for structural processing. This can be a manually intensive
      procedure, and considerably limits their utility. The purpose of this study was
      to create a vervet MRI population template, associated tissue probability maps
      (TPM), and a label atlas to facilitate true fully automated Magnetic Resonance
      Imaging (MRI) structural analyses for morphometric analyses. Structural MRI scans
      of ten vervet monkeys (Chlorocebus aethiops) scanned at three time points were
      used in this study. An unbiased population average template was created using a
      symmetric diffeomorphic registration (SyN) procedure. Skull stripping,
      segmentation, and label map generation were performed using the publically
      available rhesus INIA19 MRI template and NeuroMap label atlas. A six-class TPM
      and a six-layer two-class normalization template was created from the vervet
      segmentation for use within the Statistical Parametric Mapping (SPM) framework.
      Fully automated morphologic processing of all of the vervet MRI scans was then
      performed using the vervet TPM and vervet normalization template including skull
      stripping, segmentation and normalization. The vervet template creation procedure
      resulted in excellent skull stripping, segmentation, and NeuroMap atlas labeling
      with 720 structures successfully registered. Fully automated processing was
      accomplished for all vervet scans, demonstrating excellent skull-stripping,
      segmentation, and normalization performance. We describe creation of an unbiased
      vervet structural MRI population template and atlas. The template includes an
      associated six-class TPM and DARTEL six-layer two-class normalization template
      for true fully automated skull-stripping, segmentation, and normalization of
      vervet structural T1-weighted MRI scans. We provide the most detailed vervet
      label atlas currently available based on the NeuroMaps atlas with 720 labels
      successfully registered. We additionally describe a novel method for atlas label
      generation that capitalizes on previous work in this area using high-dimensional
      highly accurate image matching procedures for inter-species morphologic
      normalization. 

PMID- 24850580
TI  - The Symbol Digit Modalities Test as sentinel test for cognitive impairment in
      multiple sclerosis.
AB  - BACKGROUND AND PURPOSE: Cognitive impairment (CI) is found in about half of the
      multiple sclerosis (MS) population and is an important contributor to employment
      status and social functioning. CI is encountered in all disease stages and
      correlates only moderately with disease duration or Expanded Disability Status
      Scale scores. Most present neuropsychological test batteries are time-demanding
      and expensive. The Symbol Digit Modalities Test (SDMT) has been suggested as a
      screening tool for CI in MS. In this paper, we aim to assess the performance of
      the SDMT in predicting the outcome of an extensive battery. METHODS:
      Neuropsychological test results from 359 patients were assessed in a
      multidisciplinary MS center (National MS Center Melsbroek, Belgium). Using
      receiver operating characteristic curves, the performance of the SDMT in
      predicting the general cognitive outcome of the extensive Neuropsychological
      Screening Battery for MS (NSBMS) could be assessed. The performance of the SDMT
      was assessed for different levels of CI and compared with other cognitive tests.
      Finally, useful covariates were included in a logistic regression model. RESULTS:
      At a specificity of 0.60 a high sensitivity (0.91) was obtained indicating the
      potential of the SDMT as a sentinel test for CI in MS. The SDMT outperformed the
      individual tests included in the NSBMS, used as benchmark. As the logistic
      regression model did not result in a relevant improvement, it is concluded that
      most clinical variables influence both the SDMT and the NSBMS in a similar way.
      Excluding patients with possible practice effects, an optimal cutoff of 40 was
      found for the SDMT. CONCLUSION: As the SDMT is an easy, low-cost and fast test,
      this result may help to detect CI in everyday clinical practice.

PMID- 24850584
TI  - From the publisher.

PMID- 24850587
TI  - Comparison of the BISAP scores for predicting the severity of acute pancreatitis
      in Chinese patients according to the latest Atlanta classification.
AB  - BACKGROUND: The bedside index of severity in acute pancreatitis (BISAP) is a new,
      convenient, prognostic multifactor scoring system. As there were no studies
      designed to validate this system according to the latest Atlanta classification
      in China and more data are needed before clinical application, we compared BISAP,
      the Acute Physiology and Chronic Health Evaluation (APACHE) II and Ranson scoring
      systems in predicting the severity, pancreatic necrosis and mortality of acute
      pancreatitis (AP) using the latest 2012 Atlanta classification in a tertiary care
      center in China. METHODS: The medical records of all patients with AP admitted to
      our hospitals between January 2010 and June 2013 were reviewed retrospectively.
      Severe AP was defined as the persistence of organ failure for more than 48 h. The
      capacity of the BISAP, APACHE II and Ranson's score system to predict severity,
      pancreatic necrosis and mortality was evaluated using linear-by-linear
      association. The predictive accuracy of the BISAP, APACHE II and Ranson's score
      was measured as the area under the receiver operating characteristic curve (AUC).
      RESULTS: Of 155 patients enrolled in the study, 16.7% were classified as having
      severe AP, and six (3.2%) died. There were statistically significant trends for
      increasing severity (P < 0.001), PNec (P < 0.001) and mortality (P < 0.001) with
      increasing BISAP. The AUC for severity predicted by BISAP was 0.793 (95%
      confidence interval [CI] 0.700-0.886), APACHE II 0.836 (95% CI 0.744-0.928) and
      by Ranson score was 0.903 (95% CI 0.814-0.992). The AUC for PNec predicted by
      BISAP was 0.834 (95% CI 0.739-0.929), APACHE II 0.801 (95% CI 0.691-0.910) and by
      Ranson score was 0.840 (95% CI 0.741-0.939). The AUC for mortality predicted by
      BISAP was 0.791 (95% CI 0.593-0.989), APACHE II 0.812 (95% CI 0.717-0.906) and by
      Ranson score was 0.904 (95% CI 0.829-0.979). CONCLUSIONS: BISAP score may be a
      valuable source for risk stratification and prognostic prediction in Chinese
      patients with AP. A prospective and multicenter validation study is required to
      confirm our results and further our recognition of BISAP scores in AP.

PMID- 24850588
TI  - Would continuous feedback of patient's clinical outcomes to practitioners improve
      NHS psychological therapy services? Critical analysis and assessment of quality
      of existing studies.
AB  - PURPOSE: Continuous outcome monitoring studies have been conducted by one group
      of researchers in the United States, mainly in university counselling clinics. We
      completed a systematic review of continuous outcome monitoring and feedback
      during psychological therapy and assessed the quality and methodological rigour
      of existing studies to examine if the findings might be applicable to
      psychological therapy settings in the United Kingdom. METHODS: An electronic
      database literature search was carried out on studies on or after 1990 to June
      2013 using strict research criteria. Independent ratings of the quality of
      existing studies were undertaken. RESULTS: Ten studies with original data met
      inclusion criteria and two meta-analyses. Feedback improves outcomes for clients
      who are at risk of treatment failure but effect sizes diminish with more severe
      psychiatric populations. No study has followed up patients to assess maintenance
      of gains. Study quality is highly variable. Few studies included diagnostic
      information and details of randomization. Clinical Support Tools are thought to
      be helpful but how these were used was not described. CONCLUSIONS: Although
      research in continuous monitoring and feedback of clinical outcomes shows
      promising results in counselling settings, study quality, and methodological
      issues set limitations on the generalizability of the findings. PRACTITIONER
      POINTS: Feedback improves the outcome of therapy for young people with mild
      problems for those who are at risk of not improving with therapy. Feedback
      improves outcomes for those with more severe mental health problems but with
      reduced effect sizes. We do not know if improved outcomes are sustained. The
      generalizability of the findings may be limited.

PMID- 24850594
TI  - Adolescent group psychotherapy.

PMID- 24850589
TI  - Serotonin 5-HT6 receptor antagonists for the treatment of cognitive deficiency in
      Alzheimer's disease.
AB  - Alzheimer's disease (AD) is one of the most frequent causes of death and
      disability worldwide and has a significant clinical and socioeconomic impact. In
      the search for novel therapeutic strategies, serotonin 5-HT6 receptor (5-HT6R)
      has been proposed as a promising drug target for cognition enhancement in AD.
      This manuscript reviews the compelling evidence for the implication of this
      receptor in learning and memory processes. We have summarized the current status
      of the medicinal chemistry of 5-HT6R antagonists and the encouraging preclinical
      findings that demonstrate their significant procognitive behavioral effects in a
      number of learning paradigms, probably acting through modulation of multiple
      neurotransmitter systems and signaling pathways. The results of the ongoing
      clinical trials are eagerly awaited to shed some light on the validation of 5
      HT6R antagonists as a new drug class for the treatment of symptomatic cognitive
      impairment in AD, either as stand-alone therapy or in combination with
      established agents. 

PMID- 24850595
TI  - Teenage 1977-sexual revolution or evolution?

PMID- 24850597
TI  - Pancreatoduodenectomy as classic and pylorus-preserving variant: single center
      experience.
AB  - It is presented and discussed the experience of pancreatoduodenectomy for
      pancreatic head and ampullary tumors. Of 7 cases of pancreatoduodenectomy 3 were
      performed as classic Whipple procedure and 4 as modified pylorus-preserving
      variant (PPPD). It was observed 2 cases of mild pancreatic and biliary leak and 1
      patient developed abdominal wall dehiscence after the surgical site infection.
      There was no operative mortality and overall postoperative morbidity rate was
      42,8%. It is concluded,that "end-to-end" pancreaticojejunostomy with stent
      placement and the PPPD variant are the most optimal and preferred operative
      procedures at pancreatoduodenectomy cases.

PMID- 24850598
TI  - Topical diagnostics of traumatic condylar injuries and alloplastic reconstruction
      of temporomandibular joint heads.
AB  - Condylar fractures have an important place in facial traumatic injuries.
      Classification of condylar fractures according to clinical-anatomic picture is
      common in clinical practice. According to this classification there are: 1)
      fractures of mandibular joint head, aka intraarticular fractures, 2) condylar
      neck fractures or high extra articular fractures, 3) condylar base fractures.
      Radiographic imaging plays important role in diagnosing condylar fractures along
      with knowledge of clinical symptoms. We used computer tomography imaging in our
      clinical practice. Three-dimensional imaging of computer tomography gives exact
      information about location of condylar fractures, impact of fractured fragments,
      displacement of condylar head from articular fossa. This method is mostly
      important for the cases which are hard to diagnose (fractures of mandibular joint
      head, aka intraarticular fractures). For this group of patients surgical
      treatment is necessary with the method of arthroplasty. We have observed 5
      patients with bilateral, fragmented, high condylar fractures. In all cases the
      surgery was performed on both sides with bone cement and titanium mini-plates.
      Long-term effects of the treatment included observation from 6 months to 2 years.
      In all cases anatomic and functional results were good. Shape of the mandible is
      restored, opening of mouth 3-3.5 cm, absence of malocclusion.

PMID- 24850599
TI  - [Early activation of heart-operated patients as a tool for optimization of cardio
      surgery curation (review)].
AB  - During last years in foreign countries there was widely introduced tactic of
      early activation of cardio-surgery patients. Necessary components of this
      methodical approach are early finishing of post-operation artificial respiration
      and extubation of trachea, shortening of time spending in intensive therapy till
      1 day and sign out from stationary after 5 days. As a result of reducing
      hospitalization period, the curation costs are reduced significantly. Goal of
      this research was the analysis of methods of anesthesia that allow early
      extubation and activation after cardio-surgery interventions. There were analyzed
      data of protocols of anesthesia and post-operation periods for 270 patients. It
      was concluded that applied methods of anesthesia ensure adequate protection from
      operation stress and allow reduce time of post-operation artificial respiration,
      early activation of patients without reducing level of their safety. It was also
      proved that application of any type of anesthesia medicines is not influencing
      the temp of post-operation activation. Conducted research is proving the
      advisability of using tactic of early activation of patients after heart
      operations and considers this as a tool for optimization of cardio-surgery
      curation.

PMID- 24850600
TI  - [Genetic aspects of male infertility].
AB  - We examined 118 men with infertility. Among them we identified phenotypic
      syndromes associated with infertility in 4 and chromosomal abnormalities in 16.
      Further molecular genetic study of 98 infertile men found that microdeletions in
      AZFc-locus had 3, pathological AR allele had 2, CFTR gene mutation had 4 of them.
      In 37 infertile men an increased DNA fragmentation index (>20%) was found.

PMID- 24850601
TI  - [Autoimmune mechanisms toward type I collagen during parodontitis].
AB  - The article presents original data about autoimmune mechanisms according to the
      severity of the process during the chronic generalized Parodontitis. The medical
      examination of 179 patients with different forms of Parodontitis demonstrated
      that during Parodontitis the synthesis and re-synthesis of type I Collagen is
      negatively affected and as a result, type I Collagen concentration in the blood
      serum raises. In addition, the selection of antigen reactive lymphocytes
      increases toward Type I Collagen, which in turn boosts their quantity in blood
      and also stimulates the creation of auto-antibodies toward Type I Collagen. This
      is reflected by the increased quantity of auto-antibodies in the blood serum. The
      intensity of these processes amplifies as the Parodontitis inflammation becomes
      more severe. These results demonstrate that the autoimmune process develops
      toward Type I Collagen during Parodontitis and its intensity reflects the
      severity of the pathological processes in Parodontitis.

PMID- 24850602
TI  - [Prevention of complications fixed restorations in prosthetic patients with
      hypertension].
AB  - The author on the basis of clinical and laboratory methods justified, that the
      use of locally cream "Solcoseryl-Denta" persons suffering from arterial
      hypertension, increase the speed of recovery of normal epithelial layer of the
      cells of the mucous membranes of the oral cavity, and, consequently, prevents the
      development of complications in prosthetics. On the basis of research identified
      the need in developing a method of prevention of inflammatory complications in
      prosthetic patients with arterial hypertension.

PMID- 24850603
TI  - [Correction of endothelial dysfunction in patients with essential hypertension
      and type 2 diabetes].
AB  - Presence of comorbidity in patients--that is essential hypertension and type 2
      diabetes is associated with early progression of target organs affection and
      cardiovascular complications. Hyperinsulinemia and insulin resistance are some of
      the factors that determine the frequency of cardiovascular complications in type
      2 diabetes. According to some authors, endothelial dysfunction is a link between
      insulin resistance and cardiovascular diseases. To investigate severity of
      endothelial dysfunction in patients with essential hypertension and type 2
      diabetes and its correction by using a complex treatment alpha-lipoic acid we
      have examined 84 patients with essential hypertension stage II and type 2
      diabetes in a moderate condition before and after 6 months treatment. The
      patients were divided into two groups: the first one consisted of the patients
      who received only basic therapy, and another one consisted of those patients who
      in addition to basic therapy received also alpha-lipoic acid in tablets at a dose
      of 600 mg/day. After the investigation it was discovered that changes in the
      vascular wall in patients with essential hypertension and type 2 diabetes are
      characterized by increase of intima-media thickness and pulse wave velocity in
      the carotid arteries and abdominal aorta, decrease of endothelium-dependent
      vasodilation degree and increase of the levels of proinflammatory cytokines.
      Under the influence of the mentioned complex therapy in these patients it was
      found some improvement of metabolic homeostasis and correction of endothelial
      dysfunction. The effect on the structural and functional state of great vessels
      and proinflammatory cytokines, gained due to additional prescription of alpha
      lipoic acid to the patients with essential hypertension and type 2 diabetes, was
      more considerable that the one which was shown in the group of patients who
      received only standard therapy.

PMID- 24850604
TI  - [12Ala polymorphism of receptor gene, which activates proliferation by peroxisome
      alpha2, determines severity of bronchial asthma course associated with coronary
      heart disease].
AB  - The aim of the research was to detect the role of PPAR-gamma2 gene Pro12Ala
      polymorphism in the development of bronchial asthma (BA) in combination with
      coronary heart disease (CHD). BA patients in combination with coronary artery
      disease were examined in terms of anthropometric measurements, lung function,
      cycle ergometry, ECG, blood pressure, and endothelium-independent vasodilatation.
      The alleles of PPAR-gamma2 gene polymorphic region were determined; the high
      sensitivity C-reactive protein (hs-CRP) and the adhesion molecules sVCAM-1 and
      sICAM-1 in the blood were detected; the biochemical blood analysis was performed.
      It was found that patients with Ala allele in homo-and heterozygous state, as
      opposed to patients with Pro allele in homozygous variant, reveal a significantly
      higher incidence of first grade arterial hypertension and mild persistent BA;
      lower rates of heart rate were recorded; significantly higher levels of
      parameters characterizing the systemic inflammation (white blood cell count and
      hsCRP) and lower rates of adhesion molecules of sICAM-1 level, total cholesterol,
      total and indirect bilirubin were detected. Ala allele carriers in homo- and
      heterozygous state in patients with BA in combination with CHD is associated with
      the risk of overweight, mild persistent asthma and angina I FC. Thus, the carrier
      state of 12Ala allele of PPAR-gamma2 gene Pro12Ala polymorphism may be associated
      with a higher risk of developing BA against the background of CHD.

PMID- 24850605
TI  - [Quality of life of patients with chronic hepatitis C at different degrees of
      expression of mixed cryoglobulinemia].
AB  - The article investigates the quality of life of 305 patients with chronic
      hepatitis C. It was revealed that in the absence of mixed cryoglobulinemia but in
      the presence of its biochemical signs the effect of physical conditions and
      emotional state on role functioning don't differ from those of the healthy
      people. However indicators of social functioning, self-rating of mental health
      and the general state of health are decreased. Increase of the quantitative
      maintenance of the mixed cryoglobulins in blood serum of patients with chronic
      hepatitis C leads to clinical manifestations of the HCV-related cryoglobulinemia
      syndrome accompanied by the decrease of self assessment of health by patients due
      to the deterioration of influence of a physical conditions and emotional state on
      role functioning.

PMID- 24850606
TI  - [Optimization of long-term hypolipidemia treatment of patients with myocardial
      infarction in combination with non-alcoholic steatohepatitis].
AB  - In a comparative aspect, the dynamics of indices of lipidogram, functional state
      of liver and level of C-reactive of protein have been analyzed in 79 patients
      with myocardial infarction in combination with non-alcoholic steatohepatitis, who
      received a 9-months treatment by rosuvastatin of 20 mg, atorvastatin of 80 mg, as
      well as rosuvastatin of 10 mg, atorvastatin of 40 mg in combination with
      ursodeoxycholic acid (UDCA). The obtained results show the equivalent of
      hypolipidemia effectiveness of all investigated courses of statinotherapy with
      the benefit of rosuvastatin of 20 mg in increase of level of HDL cholesterol and
      combined statinotherapy with UDCA in decrease of level of triglycerides. It was
      confirmed the significant advantages of combined statinotherapy with UDCA as for
      the influence on functional state of liver and CRP level, and advantages of
      rosuvastatin of 10 mg in combination with UDCA. Thus, the combination of
      rosuvastatin of 10 mg with UDCA should be preferable in the treatment of patients
      with myocardial infarction in combination with non-alcoholic steatohepatitis from
      the positions of the effectiveness and safety. Besides, taking into account
      positive correlation between the CRP level in blood and activity of transaminases
      in the dynamics of observation it can be concluded that high activity of
      transaminases is the prognostic marker of the severity and procession of
      polymorbid pathology - myocardial infarction in combination with non-alcoholic
      steatohepatitis.

PMID- 24850607
TI  - Early repolarization as a risk factor of atrial fibrillation.
AB  - Early repolarization pattern is a common ECG pattern characterized by J-point and
      ST segment elevation in 2 or more contiguous leads. There are some opinions that
      early repolarization may be associated with some kind of arrhythmias (including
      life-threatening arrhythmias) Aim of this study was to declare correlation
      between early repolarization and atrial fibrillation. In this study participated
      patients (19-68 years old) with early repolarization and without exclusion
      criteria. Monitoring was made by helping 24h ambulatory ECG monitoring. Variables
      are expressed as mean +/- SD, The analysis was performed using Student's t test,
      statistical tests were two-tailed, and a p value < 0.05 was considered
      statistically significant. We compared rate of atrial fibrillation in patients
      with early repolarization to rate of atrial fibrillation in general population;
      The comparison of this two data shows that rate of atrial fibrillation in
      patients with early repolarization is significant higher than rate of atrial
      fibrillation in general population (7,3 fold higher; 14,6% Vs 2%). So, early
      repolarization may be considered as independent risk factor of atrial
      fibrilallation. This is principally new and very important information.

PMID- 24850608
TI  - Evaluation of state opioid substitution treatment program in Georgia.
AB  - AIMS: Evaluation of State Opioid Substitution Treatment OST (methadone and
      buprenorphine/naloxone- Addnok-N) program in Georgia and optimization of the
      routine measurement instrument. Patients were recruited from 4 Tbilisi and 5
      regional State Programs in May-October 2013. 2 structured self-questionnaires
      (one - anonymous for sensitive questions) were developed for patients to assess
      demographics, retention in treatment, mean drug dose, HIV and Hepatitis C and B
      status, illicit drug and alcohol use, social activities, crime involvement,
      health status, HIV risk behavior, treatment compliance and satisfaction. 608
      patients (7 females) were surveyed (512 - on Methadone, 96 - on
      buprenorphine/naloxone). 337 (1 female) patients completed an anonymous
      questionnaire. Mean age - 39.43+/-8.7 (21-65 years). 10 (1.64%) respondents were
      HIV positive; 448 (73.68%) - HCV+ and 24 (3.95%) - HBV+; average methadone dose -
      39.27+/-22.2mg; buprenorphine/naloxone - 7.4+/-3.6 mg; 64 (40%) of employed began
      working while in program; 365 (60%) have been in treatment for less than 1 year,
      and 146 (24%) - for 1-3 years vs. 258 (51%) out of 506 patients surveyed in 2011.
      494 (81.2%) reported improvement of social status and 508 (83.5%) - of health
      status. 305 (90.5%) out of 337 reported no- and 30 (8.9%) - reduction of criminal
      activity. 467 (76.81%) patients attended individual and 200 (32.9%)-group
      psychotherapy sessions with various frequencies. The common adverse events: sleep
      disturbances - 48.84%; weakness - 50.82%; mood disturbances - 42.44%, and
      heaviness - 36.35%. 257 (46%) reported using of alcohol; 16 - opioids; 29 -
      sedative/hypnotics; 8 - marijuana and 1 - ATS past 30 days; 55 - drug injection
      and 11 - sharing of any injection equipment past 6 months. State OST program is
      effective in Georgia in terms of reduction of illegal drug use, injection risk
      behavior and criminal activity, and on the other hand - improving of social
      activity and general health. Treatment retention is less as compared with 2011
      survey.

PMID- 24850609
TI  - [Effect of gene polymorphism of PPARgamma2 regulatory proteins on the metabolic
      syndrome in children with nonalcoholic fatty liver disease and obesity].
AB  - The aim of this study was to investigate the influence of single nucleotide
      polymorphism Pro12Ala of PPARgamma2 gene in phenotypical manifestations,
      carbohydrate and lipid metabolism, blood pressure (BP) and tumor necrosis factor
      alpha (TNF-alpha) in children with exogenous constitutional obesity (ECO) and
      nonalcoholic fatty liver disease (NAFLD). 67 children aged from 7 to 17 years
      were examined; among them 34 patients were diagnosed with NAFLD and 33 children
      with ECO. The algorithm of examination included assessment of anthropometric
      parameters, blood lipid profile, glucose indicators and immunoreactive insulin
      (IRI) on an empty stomach, the calculation of the HOMA-IR index, genetic methods
      of examination. The study of Pro12Ala polymorphism of PPARgamma2 gene showed that
      patients with NAFLD demonstrated the highest percentage in the frequency of the
      "wild genotype" Pro/Pro (88,2%) and significantly lower prevalence rate in
      frequency of allele Ala (11,8%). The presence of the polymorphic allele Ala was
      associated with lower levels of IRI, HOMA-IR index, a significant reduction of
      virtually all components of lipid metabolism, systolic blood pressure and pro
      inflammatory cytokine TNF-alpha. Children with genotype X/Ala have greater body
      weight and higher BMI as compared with homozygous carriers of Pro allele. The
      detected changes allow us to recommend the use of genetic screening to identify
      single nucleotide polymorphism Pro12Ala of PPARgamma2 gene in obese children in
      order to determine the degree of risk of metabolic disorders development and
      implement the preventive measures in a timely manner.

PMID- 24850610
TI  - Carcinogenesis--a new point of view.
AB  - Presented article suggests the novel hypothesis of carcinogenesis, where the key
      moment for all types (biological, physical, chemical) of carcinogenesis has been
      discussed. For confirmation of the hypothesis thorough theoretical analysis of
      the mechanisms of malignant transformation of cells after influence of any type
      of carcinogens and results of experiments have been presented. Hypothesis
      highlights are formulated as follows: 1) Covalent bond disorders between S+
      methionine and Fe3+ atoms in cytochrome; 2) Electron transport chain blockade
      with certain ligand after its penetration in cytochrome pocket with further
      formation of 6th coordination bond between ligand and Fe atom (in one case
      increase in mitochondrial pH precede-, and in other, it follows electron
      transport chain blockade in cytochromes); 3) Fe3+ reduction up to Fe2+ leading to
      blockade of aerobic glycolysis; 4) Decrease in enzyme (E1-TDP, oxidases etc.)
      activity due to mitochondrial pH alterations; 5) Production of S
      adenosylmethionine owing to lipoic acid amide leading to accumulation of
      homocysteine in cytoplasm with further penetration in cell nucleus producing DNA
      mutations; 6) Fe2+ wash-out from cytochrome and its deposition in ferritin.

PMID- 24850611
TI  - [Experimental basis and comparison of clinical use radio frequency energy argon
      plasma coagulation, adhesions preparation "intercoat" complex and rehabilitation
      after laparoscopic treatment of patients with polycystic ovary and tubal
      peritoneal infertility].
AB  - Aim of this study was to evaluate the efficiency of the use of radio wave energy
      and argon plasma surgery, use of "Intercoat" for the prevention of adhesions and
      use of rehabilitation complex (L-arginine, electrical stimulation of the
      fallopian tubes) in the treatment of patients with PCOS and tubal-peritoneal
      infertility. Experimental studies on 56 female rats of Wistar and clinical
      studies of 90 patients with PCOS and tubal-peritoneal infertility were undergone.
      Use of argon plasma coagulation for ovarian hemostasis characterized by the
      smallest damaging effect. Application adhesions barrier "Intercoat" prevents the
      development of adhesions II, III, IV degree. Use of argon plasma coagulation and
      ligature tuboplasty 2.1 times increases recovery of reproductive function in
      women with PCOS. Developed method of intraoperative and postoperative management
      reduces 2 times the number of patients who develop subsequent tubal pregnancy.

PMID- 24850612
TI  - Preliminary phytochemical and biological evaluation of daphne glomerata extracts.
AB  - The article reports on the phytochemical and biological potentials of leaves and
      stems of Daphne glomerata Lam. (Fam. Thymelaeaceae). Study indicated that crude
      extracts from the leaves and stems of the plant have high biological activity.
      Cytotoxicity was assessed using resazurin on an automated 96-well Fluoroskan
      Ascent F1_ plate reader (Labsystems) using excitation and emission wavelengths of
      530 nm and 590 nm, respectively. High cytotoxic activity (<1,563 ug/ml) of both
      extracts toward lung carcinoma cell lines was elucidated. The specificity of
      extracts to WS-1 human fibroblast cell lines was observed. For the first time,
      the profiles of compounds with terpenic and phenolic nature were described in
      Daphne glomerata leaves and stems MeOH extracts by TLC and (HPLC-DAD-MS)
      techniques.

PMID- 24850613
TI  - Analysis of Perilla nankinensis decne essential oil using gas chromatography
      coupled with time-of-flight mass spectrometry.
AB  - Perilla is the genus of herbaceous plants of Lamiaceae family. The essential oil
      of Perilla is believed to be essential part of the herb. It was claimed to have
      anti-inflammatory, anti-hyperlipidemia, antioxidative and antimicrobial
      activities. Apart from pharmaceutical and nutrition purposes, It is an edible
      plant frequently used as a fresh vegetable. It was also applied to produce
      perfume and cosmetics. Due to the importance of the essential oil from the P.
      nanakinensis and the lack of detailed studies of them, our work aimed
      investigation of contents of essential compositions by GC- TOF/MS method. The
      materials of the study were the aerial parts of P. nankinesis collected at full
      flowering stage, Guria Region, Georgia. A qualitative analysis of the individual
      compounds in P. nankinensis essential oil performed by gas chromatography (GC)
      coupled with time-of-flight mass spectrometer (TOF/MS) for the identification of
      the resolved peaks. 28 components, which accounted for 77,7% of the oil, were
      identified. The main components of this essential oil were 1,3,6,10
      Dodecatetraene, 3,7,11-trimethyl-, (Z,E)- (alpha-Farnesene) (34.3%),
      Caryophyllene oxide (10.2%), 1,6-Octadien-3-ol, 3,7-dimethyl- (linalool) (10.2%).
      Essential oil also contained humulene (3.9%),caryophyllene (1.9%), methyl
      salicilate (1.15%), 2-hexanoylfuran (1.0%), gernacrene (1.1%). Based on the
      results of our experimental data and literature reviews, Perilla essential oil
      can represent special interest and can be used as an important natural substance
      for obtaining medicinal and preventive products with the several biological
      activities.

PMID- 24850614
TI  - Neutralization of interleukin-9 ameliorates symptoms of experimental autoimmune
      myasthenia gravis in rats by decreasing effector T cells and altering humoral
      responses.
AB  - Interleukin-9 (IL-9) was initially thought to be a type 2 T helper (Th2)
      associated cytokine involved in the regulation of autoimmune responses by
      affecting multiple cell types. However, it was recently shown that IL-9-producing
      CD4+ T cells represent a discrete subset of Th cells, designated Th9 cells.
      Although Th9 cells have been shown to be important in many diseases, their roles
      in myasthenia gravis (MG) are unclear. The aim of this study was to determine
      whether IL-9 and Th9 cells promote the progression of experimental autoimmune
      myasthenia gravis (EAMG). The results showed that the percentage of Th9 cells
      changed during the progression of EAMG, accompanied by an up-regulation of IL-9.
      Blocking IL-9 activity with antibodies against IL-9 inhibited EAMG-associated
      pathology in rats and reduced serum anti-acetylcholine receptor IgG levels.
      Neutralization of IL-9 altered the Th subset distribution in EAMG, reducing the
      number of Th1 cells and increasing the number of regulatory T cells.
      Administration of an anti-IL-9 antibody may represent an effective therapeutic
      strategy for MG-associated pathologies or other T-cell- or B-cell-mediated
      autoimmune diseases.

PMID- 24850615
TI  - Home-based walking exercise in peripheral artery disease: 12-month follow-up of
      the GOALS randomized trial.
AB  - BACKGROUND: We studied whether a 6-month group-mediated cognitive behavioral
      (GMCB) intervention for peripheral artery disease (PAD) participants, which
      promoted home-based walking exercise, improved 6-minute walk and other outcomes
      at 12-month follow-up, 6 months after completing the intervention, compared to a
      control group. METHODS AND RESULTS: We randomized PAD participants to a GMCB
      intervention or a control group. During phase I (months 1 to 6), the intervention
      used group support and self-regulatory skills during weekly on-site meetings to
      help participants adhere to home-based exercise. The control group received
      weekly on-site lectures on topics unrelated to exercise. Primary outcomes were
      measured at the end of phase I. During phase II (months 7 to 12), each group
      received telephone contact. Compared to controls, participants randomized to the
      intervention increased their 6-minute walk distance from baseline to 12-month
      follow-up, (from 355.4 to 381.9 m in the intervention versus 353.1 to 345.6 m in
      the control group; mean difference=+34.1 m; 95% confidence interval [CI]=+14.6,
      +53.5; P<0.001) and their Walking Impairment Questionnaire (WIQ) speed score
      (from 36.1 to 46.5 in the intervention group versus 34.9 to 36.5 in the control
      group; mean difference =+8.8; 95% CI=+1.6, +16.1; P=0.018). Change in the WIQ
      distance score was not different between the 2 groups at 12-month follow-up
      (P=0.139). CONCLUSIONS: A weekly on-site GMCB intervention that promoted home
      based walking exercise intervention for people with PAD demonstrated continued
      benefit at 12-month follow-up, 6 months after the GMCB intervention was
      completed. CLINICAL TRIAL REGISTRATION URL: ClinicalTrials.gov. Unique
      identifier: NCT00693940.

PMID- 24850616
TI  - A limited form of proteus syndrome with bilateral plantar cerebriform
      collagenomas and varicose veins secondary to a mosaic AKT1 mutation.
AB  - IMPORTANCE: Proteus syndrome is an extremely rare disorder of mosaic postnatal
      overgrowth affecting multiple tissues including bone, soft tissue, and skin. It
      typically manifests in early childhood with asymmetric and progressive skeletal
      overgrowth that leads to severe distortion of the skeleton and disability. The
      genetic basis has recently been identified as a somatic activating mutation in
      the AKT1 gene, which encodes an enzyme mediating cell proliferation and
      apoptosis. OBSERVATIONS: We present a 33-year-old man who developed plantar
      cerebriform collagenomas on the soles of both feet and varicose veins in early
      childhood, in the absence of any skeletal or other connective tissue abnormality.
      Although the patient did not meet the diagnostic criteria for Proteus syndrome,
      he was found to have the c.49G>A, p.Glu17Lys AKT1 mutation in lesional skin but
      not in his blood. CONCLUSIONS AND RELEVANCE: To our knowledge, this is the
      mildest molecularly confirmed case of Proteus syndrome, occurring in the absence
      of the characteristic skeletal overgrowth. These findings extend the spectrum of
      Proteus syndrome pathological characteristics and suggest that somatic mutations
      late in development and restricted in distribution cause subtle clinical
      presentations that do not meet the published clinical criteria.

PMID- 24850617
TI  - Glechoma hederacea Suppresses RANKL-mediated Osteoclastogenesis.
AB  - Glechoma hederacea (GH), commonly known as ground-ivy or gill-over-the-ground,
      has been extensively used in folk remedies for relieving symptoms of inflammatory
      disorders. However, the molecular mechanisms underlying the therapeutic action of
      GH are poorly understood. Here, we demonstrate that GH constituents inhibit
      osteoclastogenesis by abrogating receptor activator of nuclear kappa-B ligand
      (RANKL)-induced free cytosolic Ca(2+) ([Ca(2+)]i) oscillations. To evaluate the
      effect of GH on osteoclastogenesis, we assessed the formation of multi-nucleated
      cells (MNCs), enzymatic activity of tartrate-resistant acidic phosphatase (TRAP),
      expression of nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), and
      [Ca(2+)]i alterations in response to treatment with GH ethanol extract (GHE) in
      primarily cultured bone marrow-derived macrophages (BMMs). Treatment of RANKL
      stimulated or non-stimulated BMMs with GHE markedly suppressed MNC formation,
      TRAP activity, and NFATc1 expression in a dose-dependent manner. Additionally,
      GHE treatment induced a large transient elevation in [Ca(2+)]i while suppressing
      RANKL-induced [Ca(2+)]i oscillations, which are essential for NFATc1 activation.
      GHE-evoked increase in [Ca(2+)]i was dependent on extracellular Ca(2+) and was
      inhibited by 1,4-dihydropyridine (DHP), inhibitor of voltage-gated Ca(2+)
      channels (VGCCs), but was independent of store-operated Ca(2+) channels. Notably,
      after transient [Ca(2+)] elevation, treatment with GHE desensitized the VGCCs,
      resulting in an abrogation of RANKL-induced [Ca(2+)]i oscillations and MNC
      formation. These findings demonstrate that treatment of BMMs with GHE suppresses
      RANKL-mediated osteoclastogenesis by activating and then desensitizing DHP
      sensitive VGCCs, suggesting potential applications of GH in the treatment of bone
      disorders, such as periodontitis, osteoporosis, and rheumatoid arthritis. 

PMID- 24850618
TI  - Implementation of a neuromuscular training programme in female adolescent
      football: 3-year follow-up study after a randomised controlled trial.
AB  - BACKGROUND: Neuromuscular training (NMT) has been shown to reduce anterior
      cruciate ligament injury rates in highly structured clinical trials. However,
      there is a paucity of studies that evaluate implementation of NMT programmes in
      sports. AIM: To evaluate the implementation of an NMT programme in female
      adolescent football 3 years after a randomised controlled trial (RCT). METHODS:
      Cross-sectional follow-up after an RCT using the Reach, Effectiveness, Adoption,
      Implementation, and Maintenance Sports Setting Matrix (RE-AIM SSM) framework.
      Questionnaires were sent to the Swedish Football Association (FA), to eight
      district FAs and coaches (n=303) that participated in the RCT in 2009, and
      coaches who did not participate in the RCT but were coaching female adolescent
      football teams during the 2012 season (n=496). RESULTS: Response rates were 100%
      among the FAs, 57% among trial coaches and 36% among currently active coaches.
      The reach of the intervention was high, 99% of trial coaches (control group) and
      91% of current coaches were familiar with the programme. The adoption rate was
      74% among current coaches, but programme modifications were common among coaches.
      No district FA had formal policies regarding implementation, and 87% of current
      coaches reported no club routines for programme use. Maintenance was fairly high;
      82% of trial coaches from the intervention group and 68% from the control group
      still used the programme. CONCLUSIONS: Reach and adoption of the programme was
      high among coaches. However, this study identified low programme fidelity and
      lack of formal policies for its implementation and use in clubs and district FAs.

PMID- 24850619
TI  - Symptomatic radial artery thrombosis successfully treated with endovascular
      approach via femoral access route.
AB  - Radial access has been increasingly utilized for coronary intervention due to
      higher safety profile in comparison to femoral access site with lower bleeding
      rate. Radial artery occlusion is not uncommon with radial access site. This
      usually does not lead to any harm due to ulnar artery collaterals that are
      sufficient to prevent hand ischemia and is usually left alone. However, in the
      case of significant hand ischemia, treatment is often necessary. We are reporting
      an interesting case of symptomatic radial artery thrombosis leading to arm
      ischemia that was successfully treated percutaneously using femoral access. Using
      femoral access for radial artery intervention has not been reported previously.
      This case is followed by review of the literature. 

PMID- 24850620
TI  - Limited and localized outbreak of newly emergent type 2 vaccine-derived
      poliovirus in Sichuan, China.
AB  - From August 2011 to February 2012, an outbreak caused by type 2 circulating
      vaccine-derived poliovirus (cVDPV) occurred in Aba County, Sichuan, China. During
      the outbreak, four type 2 VDPVs (>=0.6% nucleotide divergence in the VP1 region
      relative to the Sabin 2 strain) were isolated from 3 patients with acute flaccid
      paralysis (AFP) and one close contact. In addition, a type 2 pre-VDPV (0.3% to
      0.5% divergence from Sabin 2) that was genetically related to these type 2 VDPVs
      was isolated from another AFP patient. These 4 patients were all unimmunized
      children 0.7 to 1.1 years old. Nucleotide sequencing revealed that the 4 VDPV
      isolates differed from Sabin 2 by 0.7% to 1.2% in nucleotides in the VP1 region
      and shared 5 nucleotide substitutions with the pre-VDPV. All 5 isolates were
      closely related, and all were S2/S3/S2/S3 recombinants sharing common
      recombination crossover sites. Although the two major determinants of attenuation
      and temperature sensitivity phenotype of Sabin 2 (A481 in the 5' untranslated
      region and Ile143 in the VP1 protein) had reverted in all 5 isolates, one VDPV
      (strain CHN16017) still retained the temperature sensitivity phenotype.
      Phylogenetic analysis of the third coding position of the complete P1 coding
      region suggested that the cVDPVs circulated locally for about 7 months following
      the initiating oral poliovirus vaccine (OPV) dose. Our findings reinforce the
      point that cVDPVs can emerge and spread in isolated communities with immunity
      gaps and highlight the emergence risks of type 2 cVDPVs accompanying the
      trivalent OPV used. To solve this issue, it is recommended that type 2 OPV be
      removed from the trivalent OPV or that inactivated polio vaccine (IPV) be used
      instead. 

PMID- 24850621
TI  - Contributions to protection from Streptococcus pneumoniae infection using the
      monovalent recombinant protein vaccine candidates PcpA, PhtD, and PlyD1 in an
      infant murine model during challenge.
AB  - A vaccine consisting of several conserved proteins with different functions
      directing the pathogenesis of pneumonia and sepsis would be preferred for
      protection against infection by Streptococcus pneumoniae. Infants will be the
      major population targeted for next-generation pneumococcal vaccines. Here, we
      investigated the potential efficacy provided by three recombinant pneumococcal
      vaccine candidate proteins--pneumococcal histidine triad D (PhtD), detoxified
      pneumolysin derivative (PlyD1), and pneumococcal choline-binding protein A (PcpA)
      -for reducing pneumonia and sepsis in an infant mouse vaccine model. We found
      vaccination with PhtD and PcpA provided high IgG antibody titers after
      vaccination in infant mice, similar to adult mice comparators. PlyD1-specific
      total IgG was significantly lower in infant mice, with minimal boosting with the
      second and third vaccinations. Similar isotypes of IgG for PhtD and PlyD1 were
      generated in infant compared to adult mice. Although lower total specific IgG to
      all three proteins was elicited in infant than in adult mice, the infant mice
      were protected from bacteremic pneumonia and sepsis mortality (PlyD1) and had
      lower lung bacterial burdens (PcpA and PhtD) after challenge. The observed immune
      responses coupled with bacterial reductions elicited by each of the monovalent
      proteins support further testing in human infant clinical trials.

PMID- 24850622
TI  - Molecular spectroscopic studies on the interactions of rhein and emodin with
      thioglycolic acid-capped core/shell CdTe/CdS quantum dots and their analytical
      applications.
AB  - Water-soluble thioglycolic acid (TGA)-capped core/shell CdTe/CdS quantum dots
      (QDs) were synthesized. The interactions of rhein and emodin with TGA-CdTe/CdS
      QDs were evaluated by fluorescence and ultraviolet-visible absorption
      spectroscopy. Experimental results showed that the high fluorescence intensity of
      TGA-CdTe/CdS QDs could be effectively quenched in the presence of rhein (or
      emodin) at 570 nm, which may have resulted from an electron transfer process from
      excited TGA-CdTe/CdS QDs to rhein (or emodin). The quenching intensity was in
      proportion to the concentration of both rhein and emodin in a certain range.
      Under optimized conditions, the linear ranges of TGA-CdTe/CdS QDs fluorescence
      intensity versus the concentration of rhein and emodin were 0.09650-60 ug/mL and
      0.1175-70 ug/mL with a correlation coefficient of 0.9984 and 0.9965,
      respectively. The corresponding detection limits (3sigma/S) of rhein and emodin
      were 28.9 and 35.2 ng/mL, respectively. This proposed method was applied to
      determine rhein and emodin in human urine samples successfully with remarkable
      advantages such as high sensitivity, short analysis time, low cost and easy
      operation. Based on this, a simple, rapid and highly sensitive method to
      determine rhein (or emodin) was proposed.

PMID- 24850623
TI  - Breast disorders.

PMID- 24850624
TI  - Development of a plasma zinc concentration cutoff to identify individuals with
      severe zinc deficiency based on results from adults undergoing experimental
      severe dietary zinc restriction and individuals with acrodermatitis
      enteropathica.
AB  - Plasma zinc concentration (PZC) is a recommended biomarker to assess zinc status
      and the risk of zinc deficiency in populations. However, the relation between PZC
      and clinical signs of zinc deficiency remains uncertain. These analyses were
      conducted to evaluate the relation between PZC and clinical signs of zinc
      deficiency and to determine a cutoff for PZC below which individuals would have
      an increased likelihood of having clinical signs associated with zinc deficiency.
      Electronic bibliographic searches were conducted of literature indexed in PubMed,
      Embase, CINAHL Plus, and EBSCO and related to experimental zinc depletion studies
      in adults and case reports in children and adults (ages <1 mo-43 y) with
      acrodermatitis enteropathica (AE). Data extracted included demographic
      characteristics, PZCs, and the presence or absence of clinical signs likely
      associated with zinc deficiency (e.g., dermatitis, diarrhea). Mean PZC was
      significantly lower among adults consuming severely zinc-restricted diets (<1 mg
      Zn/d) who developed clinical signs compared with those who remained asymptomatic
      (36.0 +/- 16.8 vs. 67.9 +/- 13.3 MUg/dL, P < 0.034). Likewise, patients with AE
      had a lower mean PZC when symptomatic compared with post-treatment PZC when they
      were asymptomatic (38.2 +/- 20.7 vs. 102 +/- 34.7 MUg/dL, P < 0.01). Among
      individuals with restricted dietary zinc intake, PZC predicted clinical signs
      with 82% sensitivity and 92% specificity when using a cutoff of 50 MUg/dL. Among
      individuals with AE, PZC predicted clinical signs with 80% sensitivity and 89%
      specificity when applying a cutoff of 50 MUg/dL. These analyses demonstrate a
      clear relation between PZC and the presence of clinical signs associated with
      zinc deficiency among presumably healthy individuals undergoing periods of
      dietary zinc restriction, as well as in individuals with AE, further validating
      the usefulness of PZC as a biomarker of severe zinc deficiency. 

PMID- 24850625
TI  - Zinc supplementation sustained normative neurodevelopment in a randomized,
      controlled trial of Peruvian infants aged 6-18 months.
AB  - A double-blind, randomized clinical trial was conducted to determine the effects
      of prevention of zinc deficiency on cognitive and sensorimotor development during
      infancy. At 6 mo of age, infants were randomly assigned to be administered a
      daily liquid supplement containing 10 mg/d of zinc (zinc sulfate), 10 mg/d of
      iron (ferrous sulfate), and 0.5 mg/d of copper (copper oxide), or an identical
      daily liquid supplement containing only 10 mg/d of iron and 0.5 mg/d of copper.
      Various controls were implemented to ensure adherence to the supplement protocol.
      A battery of developmental assessments was administered from 6 to 18 mo of age
      that included a visual habituation/recognition memory task augmented with heart
      rate at 6, 9, and 12 mo of age; the Bayley Scales of Infant Development, 2nd
      edition (BSID2) at 6, 12, and 18 mo; the A-not-B error task at 9 and 12 mo; and
      free-play attention tasks at 12 and 18 mo. Only infants supplemented with zinc
      had the normative decline in look duration from 6 to 12 mo during habituation and
      a normative decline in shifting between objects on free-play multiple-object
      attention tasks from 12 to 18 mo of age. The 2 groups did not differ on any of
      the psychophysiologic indices, the BSID2, or the A-not-B error task. The findings
      are consistent with zinc supplementation supporting a profile of normative
      information processing and active attentional profiles during the first 2 y of
      life. This trial was registered at clinicaltrials.gov as NCT00589264. 

PMID- 24850626
TI  - Processed meat intake is unfavorably and fish intake favorably associated with
      semen quality indicators among men attending a fertility clinic.
AB  - Emerging literature suggests that men's diets may affect spermatogenesis as
      reflected in semen quality indicators, but literature on the relation between
      meat intake and semen quality is limited. Our objective was to prospectively
      examine the relation between meat intake and indicators of semen quality. Men in
      subfertile couples presenting for evaluation at the Massachusetts General
      Hospital Fertility Center were invited to participate in an ongoing study of
      environmental factors and fertility. A total of 155 men completed a validated
      food-frequency questionnaire and subsequently provided 338 semen samples over an
      18-mo period from 2007-2012. We used linear mixed regression models to examine
      the relation between meat intake and semen quality indicators (total sperm count,
      sperm concentration, progressive motility, morphology, and semen volume) while
      adjusting for potential confounders and accounting for within-person variability
      across repeat semen samples. Among the 155 men (median age: 36.1 y; 83% white,
      non-Hispanic), processed meat intake was inversely related to sperm morphology.
      Men in the highest quartile of processed meat intake had, on average, 1.7
      percentage units (95% CI: -3.3, -0.04) fewer morphologically normal sperm than
      men in the lowest quartile of intake (P-trend = 0.02). Fish intake was related to
      higher sperm count and percentage of morphologically normal sperm. The adjusted
      mean total sperm count increased from 102 million (95% CI: 80, 131) in the lowest
      quartile to 168 million (95% CI: 136, 207) sperm in the highest quartile of fish
      intake (P-trend = 0.005). Similarly, the adjusted mean percentages of
      morphologically normal sperm for men in increasing quartiles of fish intake were
      5.9 (95% CI: 5.0, 6.8), 5.3 (95% CI: 4.4, 6.3), 6.3 (95% CI: 5.2, 7.4), and 7.5
      (95% CI: 6.5, 8.5) (P-trend = 0.01). Consuming fish may have a positive impact on
      sperm counts and morphology, particularly when consumed instead of processed red
      meats. 

PMID- 24850627
TI  - The associations between emotional eating and consumption of energy-dense snack
      foods are modified by sex and depressive symptomatology.
AB  - In recent years, emotional eating (EmE) has incited substantial research interest
      as an important psychologic determinant of food intake and overweight. However,
      little is known about factors that might modulate its relations with dietary
      habits. The objective of this study was to examine the association between EmE
      and consumption of energy-dense snack food and assess the 2-way interaction of
      EmE with sex and depressive symptoms. A total of 7378 men and 22,862 women from
      the NutriNet-Sante cohort (France, 2009-2013) who completed >=6 self-reported 24
      h food records were included in this cross-sectional analysis. EmE was evaluated
      via the revised 21-item Three-Factor Eating Questionnaire. Depressive symptoms
      were assessed by the Center for Epidemiologic Studies Depression Scale. The
      associations between EmE and energy-dense food consumption were assessed by
      multivariable logistic and linear regression models adjusted for sociodemographic
      and lifestyle factors. Higher EmE was associated with higher consumption of
      energy-dense snacks and, in particular, with consumption of sweet-and-fatty foods
      across most categories studied. However, these associations were stronger in
      women with depressive symptoms (e.g., high consumption of chocolate, OR: 1.77,
      95% CI: 1.43, 2.20; cakes/biscuits/pastries, OR: 1.81, 95% CI: 1.45, 2.26)
      compared with those without depressive symptoms (e.g., high consumption of
      chocolate, OR: 1.52, 95% CI: 1.36, 1.69; cakes/biscuits/pastries, OR: 1.44, 95%
      CI: 1.29, 1.61). In contrast, the significant positive associations observed in
      men without depressive symptoms (e.g., high consumption of chocolate, OR: 1.33,
      95% CI: 1.16, 1.52; cakes/biscuits/pastries, OR: 1.28, 95% CI: 1.11, 1.48) were
      not found in men with depressive symptoms. In conclusion, in women, EmE was
      positively associated with consumption of energy-dense snack food, particularly
      in those with depressive symptoms. For men, the relation between EmE and energy
      dense snack foods was found only in those without depressive symptoms. These
      findings call for consideration of the psychologic state when targeting unhealthy
      dietary habits, especially in women. This trial was registered at
      eudract.ema.europa.eu as 2013-000929-31. 

PMID- 24850632
TI  - Dental pulp stem cells: function, isolation and applications in regenerative
      medicine.
AB  - Dental pulp stem cells (DPSCs) are a promising source of cells for numerous and
      varied regenerative medicine applications. Their natural function in the
      production of odontoblasts to create reparative dentin support applications in
      dentistry in the regeneration of tooth structures. However, they are also being
      investigated for the repair of tissues outside of the tooth. The ease of
      isolation of DPSCs from discarded or removed teeth offers a promising source of
      autologous cells, and their similarities with bone marrow stromal cells (BMSCs)
      suggest applications in musculoskeletal regenerative medicine. DPSCs are derived
      from the neural crest and, therefore, have a different developmental origin to
      BMSCs. These differences from BMSCs in origin and phenotype are being exploited
      in neurological and other applications. This review briefly highlights the source
      and functions of DPSCs and then focuses on in vivo applications across the
      breadth of regenerative medicine.

PMID- 24850634
TI  - The value of the EEG in diagnosis, treatmen,t and prognosis of childhood
      epilepsy.

PMID- 24850635
TI  - Tunable white light emission from single-phased Li2 SrSiO4 :Dy(3+) phosphors by
      co-doping with Eu(3+).
AB  - A series of single-phase full-color emitting Li2 Sr1-x-y SiO4 :xDy(3+) ,yEu(3+)
      phosphors were synthesized by solid-state reaction and characterized by X-ray
      diffraction and photoluminescence analyses. The samples showed emission peaks at
      488 nm (blue), 572 nm (yellow), 592 nm (orange) and 617 nm (red) under 393 nm
      excitation. The photoluminescence excitation spectra, comprising the Eu-O charge
      transfer band and 4f-4f transition bands of Dy(3+) and Eu(3+) , range from 200 to
      500 nm. The Commission Internationale de I'Eclairage chromaticity coordinates for
      Li2 Sr0.98-x SiO4 :0.02Dy(3+) ,xEu(3+) phosphors were simulated. By manipulating
      Eu(3+) and Dy(3+) concentrations, the color points of Li2 Sr1-x-y SiO4 :xDy(3+)
      ,yEu(3+) were tuned from the greenish-white region to white light and eventually
      to reddish-white region, demonstrating that a tunable white light can be obtained
      by Li2 Sr1-x-y SiO4 :xDy(3+) ,yEu(3+) phosphors. Li2 Sr0.98-x SiO4 :0.02Dy(3+) ,
      xEu(3+) can serve as a white-light-emitting phosphor for phosphor-converted light
      emitting diode.

PMID- 24850636
TI  - A Pediatrician's View.

PMID- 24850639
TI  - Ovarian tumors in childhood.

PMID- 24850642
TI  - Obesity - early identification and treatment.

PMID- 24850649
TI  - The other ingredient of healthcare.

PMID- 24850656
TI  - Genetic counseling.

PMID- 24850655
TI  - Somatic consequences of drug abuse among adolescents.

PMID- 24850657
TI  - Acute gastrointestinal bleeding in infants and children.

PMID- 24850660
TI  - Metabolic, endocrine and genetic disorders of children.

PMID- 24850662
TI  - Heat-induced Antigen Retrieval in Conventionally Processed Epon-embedded
      Specimens: Procedures and Mechanisms.
AB  - We studied the effectiveness of heat-induced antigen retrieval (HIAR) in
      conventionally processed, epon-embedded specimens and the mechanisms of HIAR in
      the specimens. Frozen sections were first immunostained to examine the
      possibility of using HIAR for 18 antigens to avoid the effects of epoxy resin
      embedment. The antigenicity of 7 out of 18 antigens was retrieved with
      glutaraldehyde fixation followed by osmium tetroxide treatment whereas none were
      retrieved with glutaraldehyde fixation without post-osmication. Six antigens also
      exhibited positive immunostaining in semi-thin epon sections when the sections
      were deplasticized with sodium ethoxide followed by autoclaving. In the
      immunoelectron microscopy with the post-embedding method, positive reactions with
      fine ultrastructures were obtained using HIAR without deplasticization. These
      results suggested that osmium tetroxide binds to ethylene double bonds (which are
      introduced into protein crosslinks by glutaraldehyde) and forms an extremely
      stable resonance interaction with the Schiff bases, thus destabilizing the
      protein crosslinks. Heating also further degrades these crosslinks. The present
      study demonstrated that archival epon blocks can be useful resources for
      immunohistochemical studies for both light and electron microscopy. 

PMID- 24850664
TI  - Care of the pregnant adolescent.

PMID- 24850663
TI  - Immunohistological insight into the correlation between neuropilin-1 and
      epithelial-mesenchymal transition markers in epithelial ovarian cancer.
AB  - The mechanism by which neuropilin-1 (NRP-1) induces malignancy in Epithelial
      Ovarian Cancer (EOC) is still unknown. This study is the first to demonstrate the
      relationship between NRP-1 expression and EMT markers vimentin, N-cadherin, E
      cadherin and Slug. We used tissue microarrays containing the three main subtypes
      of EOC tumors: serous, mucinous cystadenocarcinoma and endometrioid
      adenocarcinoma and representative cases retrieved from our pathology archives.
      Immunohistochemistry was performed to detect the expression levels and location
      of NRP-1 and the aforementioned EMT proteins. NRP-1 was mainly expressed on
      cancer cells but not in normal ovarian surface epithelium (OSE). The
      Immunoreactive Scoring (IRS) values revealed that the expression of NRP-1, Slug
      and E-cadherin in the malignant subtypes of ovarian tissues was significantly
      higher (5.18 +/- 0.64, 4.84 +/- 0.7, 4.98 +/- 0.68, respectively) than their
      expression in the normal and benign tissues (1.04 +/- 0.29, 0.84 +/- 0.68, 1.71
      +/- 0.66, respectively), with no significant differences among the studied
      subtypes. Vimentin was expressed in the cancer cell component of 43% of tumors
      and it was exclusively localized in the stroma of all mucinous tumors. The
      Spearman's rho value indicated that NRP-1 is positively related to the EMT
      markers E-cadherin and Slug. This notion might indicate that NRP-1 is a partner
      in the EMT process in EOC tumors. 

PMID- 24850665
TI  - Local cell interactions and self-amplifying individual cell ingression drive
      amniote gastrulation.
AB  - Gastrulation generates three layers of cells (ectoderm, mesoderm, endoderm) from
      a single sheet, while large scale cell movements occur across the entire embryo.
      In amniote (reptiles, birds, mammals) embryos, the deep layers arise by
      epithelial-to-mesenchymal transition (EMT) at a morphologically stable midline
      structure, the primitive streak (PS). We know very little about how these events
      are controlled or how the PS is maintained despite its continuously changing
      cellular composition. Using the chick, we show that isolated EMT events and
      ingression of individual cells start well before gastrulation. A Nodal-dependent
      'community effect' then concentrates and amplifies EMT by positive feedback to
      form the PS as a zone of massive cell ingression. Computer simulations show that
      a combination of local cell interactions (EMT and cell intercalation) is
      sufficient to explain PS formation and the associated complex movements globally
      across a large epithelial sheet, without the need to invoke long-range
      signalling.DOI: http://dx.doi.org/10.7554/eLife.01817.001. 

PMID- 24850667
TI  - Application of silver nanoparticles to the chemiluminescence determination of
      cefditoren pivoxil using the luminol-ferricyanide system.
AB  - A new simple, accurate and sensitive sequential injection analysis
      chemiluminescence (CL) detection method for the determination of cefditoren
      pivoxil (CTP) has been developed. The developed method was based on the
      enhancement effect of silver nanoparticles on the CL signal arising from a
      luminol-potassium ferricyanide reaction in the presence of CTP. The optimum
      conditions relevant to the effect of luminol, potassium ferricyanide and silver
      nanoparticle concentrations were investigated. The proposed method showed linear
      relationships between relative CL intensity and the investigated drug
      concentration at the range 0.001-5000 ng/mL, (r = 0.9998, n = 12) with a
      detection limit of 0.5 pg/mL and quantification limit of 0.001 ng/mL. The
      relative standard deviation was 1.6%. The proposed method was employed for the
      determination of CTP in bulk drug, in its pharmaceutical dosage forms and
      biological fluids such as human serum and urine. The interference of some common
      additive compounds such as glucose, lactose, starch, talc and magnesium stearate
      was investigated. In addition, the interference of some related cephalosporins
      was tested. No interference was recorded. The obtained sequential injection
      analysis-CL results were statistically compared with those from a reported method
      and did not show any significant differences.

PMID- 24850668
TI  - Drug therapy of obesity in children.

PMID- 24850675
TI  - A manual for residential and day treatment of children.

PMID- 24850670
TI  - Mapping collaboration networks in the world of Autism Research.
AB  - In the era of globalization and with the emergence of autism spectrum disorder as
      a global concern, the landscape of autism research has expanded to encompass much
      of the world. Here, we seek to provide an overview of the world of autism
      research, by documenting collaboration underlying the International Meeting for
      Autism Research (IMFAR), the pre-eminent annual scientific meeting devoted to the
      presentation of the latest autism research. We analyzed published abstracts
      presented at IMFAR meetings, between 2008 and 2013, to determine patterns of
      collaboration. We described collaboration networks on the individual,
      institutional, and international levels, and visually depicted these results on
      spatial network maps. Consistent with findings from other scientific disciplines,
      we found that collaboration is correlated with research productivity.
      Collaborative hotspots of autism research throughout the years were clustered on
      the East and West coasts of the U.S., Canada, and northern Europe. In years when
      conferences were held outside of North America, the proportion of abstracts from
      Europe and Asia increased. While IMFAR has traditionally been dominated by a
      large North American presence, greater global representation may be attained by
      shifting meeting locations to other regions of the world.

PMID- 24850677
TI  - Hypothalamic releasing factors.

PMID- 24850679
TI  - Emotional factors in pediatric practice.

PMID- 24850680
TI  - Current approaches to the autistic child.

PMID- 24850685
TI  - A pediatrician's view.

PMID- 24850687
TI  - Delayed onset of neonatal drug withdrawal symptoms.

PMID- 24850689
TI  - Childhood head injuries and the skull roentgenogram.

PMID- 24850696
TI  - Group therapy sessions as part of treatment of children with cancer.

PMID- 24850697
TI  - Acute leukemia in children.

PMID- 24850699
TI  - Determination of paraquat in vegetables using HPLC-MS-MS.
AB  - A simple, sensitive, reliable and economical method was developed for the
      determination of paraquat (a widely used herbicide) in four edible vegetables
      (cabbage, lettuce, spinach and Chinese cabbage) using high-performance liquid
      chromatography-tandem mass spectrometry (HPLC-MS-MS). The samples were extracted
      with water under sonication and cleaned up by weak cation exchange solid-phase
      extraction. Chromatographic separation of paraquat was achieved on a hydrophilic
      interaction liquid chromatography column (2.1 * 100 mm, 3 um) with a gradient
      program using 10 mM ammonium acetate in 0.1% formic acid and acetonitrile as
      mobile phase. The low salt concentration used in the eluting buffer ensured
      extended LC-MS analysis of paraquat in different matrices without the necessity
      of frequent source cleaning. The validity of the developed method was evaluated
      by spiking paraquat in four edible vegetables at 50 and 500 ng g(-1). Recovery
      ranged from 43.6 to 73.5%. The limit of detection is 0.94 ng g(-1). With the
      developed method, the kinetic of paraquat entering plant tissue was also
      evaluated. 

PMID- 24850700
TI  - Simultaneous determination of seven synthetic colorants in wine by dispersive
      micro-solid-phase extraction coupled with reversed-phase high-performance liquid
      chromatography.
AB  - A novel and effective dispersive micro-solid-phase extraction (d-u-SPE) using
      ethanediamine-functionalized magnetic Fe3O4 polymer (EDA-MP) as an efficient
      adsorbent in wine sample was developed. Based on this, a simple and time-saving
      analytical method for the simultaneous determination of seven synthetic colorants
      (i.e., tartrazine, amaranth, carmine, sunset yellow, allura red, brilliant blue
      and erythrosine) in wine by reversed-phase high-performance liquid chromatography
      with an ultraviolet detector was established. The experimental parameters,
      including the chromatographic retention behavior of studied synthetic colorants,
      the effect of the usage amount of cross-linking monomer, the effect of the usage
      amount of EDA-MP on the recovery and the recyclability of the adsorbents, were
      studied in detail. The results showed that the EDA-MP could be reused efficiently
      at least six times. Under optimized conditions, the recoveries for all analytes
      were in the range of 88.6-105.2%, with the intraday relative standard deviations
      (RSDs) ranging from 2.1 to 8.2% and the interday RSDs ranging from 3.4 to 8.7%,
      and all the analytes had good linearities in the tested ranges with correlation
      coefficients (r(2)) >0.9995. The limits of quantification for seven synthetic
      colorants were between 0.12 and 0.45 mg L(-1). The developed method was
      successfully applied to wine samples, and it was confirmed that the EDA-MP
      particles were highly effective d-u-SPE materials. 

PMID- 24850703
TI  - Efficacy of triphala mouth rinse (aqueous extracts) on dental plaque and
      gingivitis in children.
AB  - AIM: The aim of the present study was to evaluate the efficacy of triphala mouth
      rinse (aqueous) in the reduction of plaque and gingivitis among children.
      METHODS: The study was a randomized, double-blinded, controlled trial, with a
      total of 60 school children (n = 30 in each group; triphala and chlorhexidine
      groups). Plaque and gingival indices were used to evaluate baseline and follow-up
      plaque and gingivitis. RESULTS: A total of 57 children completed the study. Both
      chlorhexidine and triphala groups showed significantly lower mean gingival and
      plaque index scores at follow up than baseline (P < 0.001). There was no
      significant difference in the percentage change in the mean gingival index
      between the two groups (P = 0.826). The percentage change in the mean plaque
      index was significantly higher in the chlorhexidine group compared to the
      triphala group (P = 0.048). CONCLUSION: The effectiveness of triphala in the
      reduction of plaque and gingivitis was comparable to chlorhexidine, and can be
      used for short-term purposes without potential side-effects. It is a cost
      effective alternative in reducing plaque and gingivitis.

PMID- 24850704
TI  - A program of weight reduction in children.

PMID- 24850708
TI  - Radiologic evaluation of childhood urinary tract infection.

PMID- 24850709
TI  - A Pediatrician's View.

PMID- 24850711
TI  - Treatment and rehabilitation of the young drug abuser.

PMID- 24850712
TI  - Emotional factors in pediatric practice.

PMID- 24850716
TI  - Acute upper-airway obstruction: clinicoradiologic approach.

PMID- 24850719
TI  - Rapid proliferation and differentiation impairs the development of memory CD8+ T
      cells in early life.
AB  - Neonates often generate incomplete immunity against intracellular pathogens,
      although the mechanism of this defect is poorly understood. An important question
      is whether the impaired development of memory CD8+ T cells in neonates is due to
      an immature priming environment or lymphocyte-intrinsic defects. In this article,
      we show that neonatal and adult CD8+ T cells adopted different fates when
      responding to equal amounts of stimulation in the same host. Whereas adult CD8+ T
      cells differentiated into a heterogeneous pool of effector and memory cells,
      neonatal CD8+ T cells preferentially gave rise to short-lived effector cells and
      exhibited a distinct gene expression profile. Surprisingly, impaired neonatal
      memory formation was not due to a lack of responsiveness, but instead because
      neonatal CD8+ T cells expanded more rapidly than adult cells and quickly became
      terminally differentiated. Collectively, these findings demonstrate that neonatal
      CD8+ T cells exhibit an imbalance in effector and memory CD8+ T cell
      differentiation, which impairs the formation of memory CD8+ T cells in early
      life.

PMID- 24850720
TI  - The combined role of galactose-deficient IgA1 and streptococcal IgA-binding M
      Protein in inducing IL-6 and C3 secretion from human mesangial cells:
      implications for IgA nephropathy.
AB  - IgA nephropathy (IgAN) is characterized by mesangial cell proliferation and
      extracellular matrix expansion associated with immune deposits consisting of
      galactose-deficient polymeric IgA1 and C3. We have previously shown that IgA
      binding regions of streptococcal M proteins colocalize with IgA in mesangial
      immune deposits in patients with IgAN. In the present study, the IgA-binding M4
      protein from group A Streptococcus was found to bind to galactose-deficient
      polymeric IgA1 with higher affinity than to other forms of IgA1, as shown by
      surface plasmon resonance and solid-phase immunoassay. The M4 protein was
      demonstrated to bind to mesangial cells not via the IgA-binding region but rather
      via the C-terminal region, as demonstrated by flow cytometry. IgA1 enhanced
      binding of M4 to mesangial cells, but not vice versa. Costimulation of human
      mesangial cells with M4 and galactose-deficient polymeric IgA1 resulted in a
      significant increase in IL-6 secretion compared with each stimulant alone.
      Galactose-deficient polymeric IgA1 alone, but not M4, induced C3 secretion from
      the cells, and costimulation enhanced this effect. Additionally, costimulation
      enhanced mesangial cell proliferation compared with each stimulant alone. These
      results indicate that IgA-binding M4 protein binds preferentially to galactose
      deficient polymeric IgA1 and that these proteins together induce excessive
      proinflammatory responses and proliferation of human mesangial cells. Thus,
      tissue deposition of streptococcal IgA-binding M proteins may contribute to the
      pathogenesis of IgAN. 

PMID- 24850721
TI  - Macrophages engulfing apoptotic cells produce nonclassical retinoids to enhance
      their phagocytic capacity.
AB  - Previous work in our laboratory has shown that transglutaminase 2 (TG2) acting as
      a coreceptor for integrin beta3 is required for proper phagocytosis of apoptotic
      cells. In the absence of TG2, systemic lupus erythematosus-like autoimmunity
      develops in mice, similarly to other mice characterized by a deficiency in the
      clearance of apoptotic cells. In this study, we demonstrate that increasing TG2
      expression alone in wild-type macrophages is not sufficient to enhance
      engulfment. However, during engulfment, the lipid content of the apoptotic cells
      triggers the lipid-sensing receptor liver X receptor (LXR), which in response
      upregulates the expression of the phagocytic receptor Mer tyrosine kinase and the
      phagocytosis-related ABCA1, and that of retinaldehyde dehydrogenases leading to
      the synthesis of a nonclassical retinoid. Based on our retinoid analysis, this
      compound might be a dihydro-retinoic acid derivative. The novel retinoid then
      contributes to the upregulation of further phagocytic receptors including TG2 by
      ligating retinoic acid receptors. Inhibition of retinoid synthesis prevents the
      enhanced phagocytic uptake induced by LXR ligation. Our data indicate that
      stimulation of LXR enhances the engulfment of apoptotic cells via regulating
      directly and indirectly the expression of a range of phagocytosis-related
      molecules, and its signaling pathway involves the synthesis of a nonclassical
      retinoid. We propose that retinoids could be used for enhancing the phagocytic
      capacity of macrophages in diseases such as systemic lupus erythematosus, where
      impaired phagocytosis of apoptotic cells plays a role in the pathogenesis of the
      disease. 

PMID- 24850722
TI  - Chemokines as novel and versatile reagents for flow cytometry and cell sorting.
AB  - Cell therapy regimens are frequently compromised by low-efficiency cell homing to
      therapeutic niches. Improvements in this regard would enhance effectiveness of
      clinically applicable cell therapy. The major regulators of tissue-specific
      cellular migration are chemokines, and therefore selection of therapeutic
      cellular populations for appropriate chemokine receptor expression would enhance
      tissue-homing competence. A number of practical considerations preclude the use
      of Abs in this context, and alternative approaches are required. In this study,
      we demonstrate that appropriately labeled chemokines are at least as effective in
      detecting their cognate receptors as commercially available Abs. We also
      demonstrate the utility of biotinylated chemokines as cell-sorting reagents.
      Specifically, we demonstrate, in the context of CCR7 (essential for lymph node
      homing of leukocytes), the ability of biotinylated CCL19 with magnetic bead
      sorting to enrich for CCR7-expressing cells. The sorted cells demonstrate
      improved CCR7 responsiveness and lymph node-homing capability, and the sorting is
      effective for both T cells and dendritic cells. Importantly, the ability of
      chemokines to detect CCR7, and sort for CCR7 positivity, crosses species being
      effective on murine and human cells. This novel approach to cell sorting is
      therefore inexpensive, versatile, and applicable to numerous cell therapy
      contexts. We propose that this represents a significant technological advance
      with important therapeutic implications. 

PMID- 24850723
TI  - Class II MHC/peptide interaction in Leishmania donovani infection: implications
      in vaccine design.
AB  - We show that Leishmania donovani-infected macrophages (MPhis) are capable of
      stimulating MHC class II (MHC-II)-restricted T cells at 6 h of infection. At 48
      h, infected MPhis (I-MPhis) failed to stimulate MHC-II-restricted T cells but not
      MHC class I-restricted ones, in contrast to normal MPhis. Such I-MPhis could
      stimulate T cells at a higher Ag concentration, indicating that general Ag
      processing and trafficking of peptide-MHC-II complexes are not defective.
      Analysis of the kinetic parameters, like "kon" and "koff," showed that peptide
      MHC-II complex formation is compromised in I-MPhis compared with normal MPhis.
      This indicates interference in loading of the cognate peptide to MHC-II, which
      may be due to the presence of a noncognate molecule. This notion received support
      from the finding that exposure of I-MPhis to low pH or treatment with 2-(1
      adamantyl)-ethanol, a molecule that favors peptide exchange, led to T cell
      activation. When treated with 2-(1-adamantyl)-ethanol, splenocytes from 8 wk
      infected BALB/c mice showed significantly higher antileishmanial T cell expansion
      in vitro compared with untreated controls. Hence, it is tempting to speculate
      that high, but not low, concentrations of cognate peptide may favor peptide
      exchange in I-MPhis, leading to expansion of the antileishmanial T cell
      repertoire. The results suggest that a high Ag dose may overcome compromised T
      cell responses in visceral leishmaniasis, and this has an important implication
      in therapeutic vaccine design. 

PMID- 24850724
TI  - The role of endogenous IFN-beta in the regulation of Th17 responses in patients
      with relapsing-remitting multiple sclerosis.
AB  - IFN-beta has been used as a first-line therapy for relapsing-remitting multiple
      sclerosis (RRMS). Because only a few studies have addressed the role of
      endogenous IFN-beta in the pathogenesis of the disease, our objective was to
      characterize its role in the transcriptional regulation of pathogenic Th17
      cytokines in patients with RRMS. In vitro studies have demonstrated that IFN-beta
      inhibits IL-17A, IL-17F, IL-21, IL-22, and IFN-gamma secretion in CD4(+)
      lymphocytes through the induction of suppressor of cytokine secretion 1 and
      suppressor of cytokine secretion 3. We found that patients with RRMS have
      increased serum and cerebrospinal fluid Th17 (IL-17A and IL-17F) cytokine levels
      in comparison with the control subjects, suggesting that deficient endogenous IFN
      beta secretion or signaling can contribute to the dysregulation of those
      pathogenic cytokines in CD4(+) cells. We identified that the endogenous IFN-beta
      from serum of RRMS patients induced a significantly lower IFN-inducible gene
      expression in comparison with healthy controls. In addition, in vitro studies
      have revealed deficient endogenous and exogenous IFN-beta signaling in the CD4(+)
      cells derived from patients with MS. Interestingly, upon inhibition of the
      endogenous IFN-beta signaling by silencing IFN regulatory factor (IRF) 7 gene
      expression, the resting CD4(+) T cells secreted significantly higher level of IL
      17A, IL-17F, IL-21, IL-22, and IL-9, suggesting that endogenous IFN-beta
      suppresses the secretion of these pathogenic cytokines. In vivo recombinant IFN
      beta-1a treatment induced IFNAR1 and its downstream signaling molecules' gene
      expression, suggesting that treatment reconstitutes a deficient endogenous IFN
      beta regulation of the CD4(+) T cells' pathogenic cytokine production in patients
      with MS. 

PMID- 24850725
TI  - Signal transduction by different forms of the gammadelta T cell-specific pattern
      recognition receptor WC1.
AB  - WC1 coreceptors are scavenger receptor cysteine-rich (SRCR) family members,
      related to T19 in sheep, SCART in mice, and CD163c-alpha in humans, and form a 13
      member subfamily in cattle exclusively expressed on gammadelta T cells.
      Subpopulations of gammadelta T cells are defined by anti-WC1 mAbs and respond to
      different pathogen species accordingly. In this study, variegated WC1 gene
      expression within subpopulations and differences in signaling and cell activation
      due to endodomain sequences are described. The endodomains designated types I to
      III differ by a 15- or 18-aa insert in type II and an additional 80 aa containing
      an additional eight tyrosines for type III. Anti-WC1 mAbs enhanced cell
      proliferation of gammadelta T cells when cross-linked with the TCR regardless of
      the endodomain sequences. Chimeric molecules of human CD4 ectodomain with WC1
      endodomains transfected into Jurkat cells showed that the tyrosine
      phosphorylation of the type II was the same as that of the previously reported
      archetypal sequence (type I) with only Y24EEL phosphorylated, whereas for type
      III only Y199DDV and Y56TGD were phosphorylated despite conservation of the
      Y24EEL/Y24QEI and Y199DDV/I tyrosine motifs among the three types. Time to
      maximal phosphorylation was more rapid with type III endodomains and sustained
      longer. Differences in tyrosine phosphorylation were associated with differences
      in function in that cross-linking of type III chimeras with TCR resulted in
      significantly greater IL-2 production. Identification of differences in the
      signal transduction through the endodomains of WC1 contributes to understanding
      the functional role of the WC1 coreceptors in the gammadelta T cell responses. 

PMID- 24850726
TI  - Inhibition of arenavirus infection by a glycoprotein-derived peptide with a novel
      mechanism.
AB  - The family Arenaviridae includes a number of viruses of public health importance,
      such as the category A hemorrhagic fever viruses Lassa virus, Junin virus,
      Machupo virus, Guanarito virus, and Sabia virus. Current chemotherapy for
      arenavirus infection is limited to the nucleoside analogue ribavirin, which is
      characterized by considerable toxicity and treatment failure. Using Pichinde
      virus as a model arenavirus, we attempted to design glycoprotein-derived fusion
      inhibitors similar to the FDA-approved anti-HIV peptide enfuvirtide. We have
      identified a GP2-derived peptide, AVP-p, with antiviral activity and no acute
      cytotoxicity. The 50% inhibitory dose (IC50) for the peptide is 7 MUM, with
      complete inhibition of viral plaque formation at approximately 20 MUM, and its
      antiviral activity is largely sequence dependent. AVP-p demonstrates activity
      against viruses with the Old and New World arenavirus viral glycoprotein complex
      but not against enveloped viruses of other families. Unexpectedly, fusion assays
      reveal that the peptide induces virus-liposome fusion at neutral pH and that the
      process is strictly glycoprotein mediated. As observed in cryo-electron
      micrographs, AVP-p treatment causes morphological changes consistent with fusion
      protein activation in virions, including the disappearance of prefusion
      glycoprotein spikes and increased particle diameters, and fluorescence microscopy
      shows reduced binding by peptide-treated virus. Steady-state fluorescence
      anisotropy measurements suggest that glycoproteins are destabilized by peptide
      induced alterations in viral membrane order. We conclude that untimely deployment
      of fusion machinery by the peptide could render virions less able to engage in on
      pathway receptor binding or endosomal fusion. AVP-p may represent a potent,
      highly specific, novel therapeutic strategy for arenavirus infection. IMPORTANCE:
      Because the only drug available to combat infection by Lassa virus, a highly
      pathogenic arenavirus, is toxic and prone to treatment failure, we identified a
      peptide, AVP-p, derived from the fusion glycoprotein of a nonpathogenic model
      arenavirus, which demonstrates antiviral activity and no acute cytotoxicity. AVP
      p is unique among self-derived inhibitory peptides in that it shows broad,
      specific activity against pseudoviruses bearing Old and New World arenavirus
      glycoproteins but not against viruses from other families. Further, the peptide's
      mechanism of action is highly novel. Biochemical assays and cryo-electron
      microscopy indicate that AVP-p induces premature activation of viral fusion
      proteins through membrane perturbance. Peptide treatment, however, does not
      increase the infectivity of cell-bound virus. We hypothesize that prematurely
      activated virions are less fit for receptor binding and membrane fusion and that
      AVP-p may represent a viable therapeutic strategy for arenavirus infection.

PMID- 24850727
TI  - E1-mediated recruitment of a UAF1-USP deubiquitinase complex facilitates human
      papillomavirus DNA replication.
AB  - The human papillomavirus (HPV) E1 helicase promotes viral DNA replication through
      its DNA unwinding activity and association with host factors. The E1 proteins
      from anogenital HPV types interact with the cellular WD repeat-containing factor
      UAF1 (formerly known as p80). Specific amino acid substitutions in E1 that impair
      this interaction inhibit maintenance of the viral episome in immortalized
      keratinocytes and reduce viral DNA replication by up to 70% in transient assays.
      In this study, we determined by affinity purification of UAF1 that it interacts
      with three deubiquitinating enzymes in C33A cervical carcinoma cells: USP1, a
      nuclear protein, and the two cytoplasmic enzymes USP12 and USP46.
      Coimmunoprecipitation experiments indicated that E1 assembles into a ternary
      complex with UAF1 and any one of these three USPs. Moreover, expression of E1
      leads to a redistribution of USP12 and USP46 from the cytoplasm to the nucleus.
      Chromatin immunoprecipitation studies further revealed that E1 recruits these
      threes USPs to the viral origin in association with UAF1. The function of USP1,
      USP12, and USP46 in viral DNA replication was investigated by overproduction of
      catalytically inactive versions of these enzymes in transient assays. All three
      dominant negative USPs reduced HPV31 DNA replication by up to 60%, an effect that
      was specific, as it was not observed in assays performed with a truncated E1
      lacking the UAF1-binding domain or with bovine papillomavirus 1 E1, which does
      not bind UAF1. These results highlight the importance of the USP1, USP12, and
      USP46 deubiquitinating enzymes in anogenital HPV DNA replication. IMPORTANCE:
      Human papillomaviruses are small DNA tumor viruses that induce benign and
      malignant lesions of the skin and mucosa. HPV types that infect the anogenital
      tract are the etiological agents of cervical cancer, the majority of anal
      cancers, and a growing proportion of head-and-neck cancers. Replication of the
      HPV genome requires the viral protein E1, a DNA helicase that also interacts with
      host factors to promote viral DNA synthesis. We previously reported that the E1
      helicase from anogenital HPV types associates with the WD40 repeat-containing
      protein UAF1. Here, we show that UAF1 bridges the interaction of E1 with three
      deubiquitinating enzymes, USP1, USP12, and USP46. We further show that these
      deubiquitinases are recruited by E1/UAF1 to the viral origin of DNA replication
      and that overexpression of catalytically inactive versions of these enzymes
      reduces viral DNA replication. These results highlight the need for an E1
      associated deubiquitinase activity in anogenital HPV genome replication.

PMID- 24850728
TI  - Genome-wide small interfering RNA screens reveal VAMP3 as a novel host factor
      required for Uukuniemi virus late penetration.
AB  - The Bunyaviridae constitute a large family of enveloped animal viruses, many of
      which are important emerging pathogens. How bunyaviruses enter and infect
      mammalian cells remains largely uncharacterized. We used two genome-wide
      silencing screens with distinct small interfering RNA (siRNA) libraries to
      investigate host proteins required during infection of human cells by the
      bunyavirus Uukuniemi virus (UUKV), a late-penetrating virus. Sequence analysis of
      the libraries revealed that many siRNAs in the screens inhibited infection by
      silencing not only the intended targets but additional genes in a microRNA
      (miRNA)-like manner. That the 7-nucleotide seed regions in the siRNAs can cause a
      perturbation in infection was confirmed by using synthetic miRNAs (miRs). One of
      the miRs tested, miR-142-3p, was shown to interfere with the intracellular
      trafficking of incoming viruses by regulating the v-SNARE VAMP3, a strong hit
      shared by both siRNA screens. Inactivation of VAMP3 by the tetanus toxin led to a
      block in infection. Using fluorescence-based techniques in fixed and live cells,
      we found that the viruses enter VAMP3(+) endosomal vesicles 5 min after
      internalization and that colocalization was maximal 15 min thereafter. At this
      time, LAMP1 was associated with the VAMP3(+) virus-containing endosomes. In cells
      depleted of VAMP3, viruses were mainly trapped in LAMP1-negative compartments.
      Together, our results indicated that UUKV relies on VAMP3 for penetration,
      providing an indication of added complexity in the trafficking of viruses through
      the endocytic network. IMPORTANCE: Bunyaviruses represent a growing threat to
      humans and livestock globally. Unfortunately, relatively little is known about
      these emerging pathogens. We report here the first human genome-wide siRNA
      screens for a bunyavirus. The screens resulted in the identification of 562 host
      cell factors with a potential role in cell entry and virus replication. To
      demonstrate the robustness of our approach, we confirmed and analyzed the role of
      the v-SNARE VAMP3 in Uukuniemi virus entry and infection. The information gained
      lays the basis for future research into the cell biology of bunyavirus infection
      and new antiviral strategies. In addition, by shedding light on serious caveats
      in large-scale siRNA screening, our experimental and bioinformatics procedures
      will be valuable in the comprehensive analysis of past and future high-content
      screening data.

PMID- 24850729
TI  - Human immunodeficiency virus reverse transcriptase displays dramatically higher
      fidelity under physiological magnesium conditions in vitro.
AB  - The fidelity of human immunodeficiency virus (HIV) reverse transcriptase (RT) has
      been a subject of intensive investigation. The mutation frequencies for the
      purified enzyme in vitro vary widely but are typically in the 10(-4) range (per
      nucleotide addition), making the enzyme severalfold less accurate than most
      polymerases, including other RTs. This has often been cited as a factor in HIV's
      accelerated generation of genetic diversity. However, cellular experiments
      suggest that HIV does not have significantly lower fidelity than other
      retroviruses and shows a mutation frequency in the 10(-5) range. In this report,
      we reconcile, at least in part, these discrepancies by showing that HIV RT
      fidelity in vitro is in the same range as cellular results from experiments
      conducted with physiological (for lymphocytes) concentrations of free Mg(2+)
      (~0.25 mM) and is comparable to Moloney murine leukemia virus (MuLV) RT fidelity.
      The physiological conditions produced mutation rates that were 5 to 10 times
      lower than those obtained under typically employed in vitro conditions optimized
      for RT activity (5 to 10 mM Mg(2+)). These results were consistent in both
      commonly used lacZalpha complementation and steady-state fidelity assays.
      Interestingly, although HIV RT showed severalfold-lower fidelity under high
      Mg(2+) (6 mM) conditions, MuLV RT fidelity was insensitive to Mg(2+). Overall,
      the results indicate that the fidelity of HIV replication in cells is compatible
      with findings of experiments carried out in vitro with purified HIV RT, providing
      more physiological conditions are used. IMPORTANCE: Human immunodeficiency virus
      rapidly evolves through the generation and subsequent selection of mutants that
      can circumvent the immune response and escape drug therapy. This process is
      fueled, in part, by the presumably highly error-prone HIV polymerase reverse
      transcriptase (RT). Paradoxically, results of studies examining HIV replication
      in cells indicate an error frequency that is ~10 times lower than the rate for RT
      in the test tube, which invokes the possibility of factors that make RT more
      accurate in cells. This study brings the cellular and test tube results in closer
      agreement by showing that HIV RT is not more error prone than other RTs and, when
      assayed under physiological magnesium conditions, has a much lower error rate
      than in typical assays conducted using conditions optimized for enzyme activity.

PMID- 24850730
TI  - Association between latent proviral characteristics and immune activation in
      antiretrovirus-treated human immunodeficiency virus type 1-infected adults.
AB  - Generalized immune activation during HIV infection is associated with an
      increased risk of cardiovascular disease, neurocognitive disease, osteoporosis,
      metabolic disorders, and physical frailty. The mechanisms driving this immune
      activation are poorly understood, particularly for individuals effectively
      treated with antiretroviral medications. We hypothesized that viral
      characteristics such as sequence diversity may play a role in driving HIV
      associated immune activation. We therefore sequenced proviral DNA isolated from
      peripheral blood mononuclear cells from HIV-infected individuals on fully
      suppressive antiretroviral therapy. We performed phylogenetic analyses,
      calculated viral diversity and divergence in the env and pol genes, and
      determined coreceptor tropism and the frequency of drug resistance mutations.
      Comprehensive immune profiling included quantification of immune cell subsets,
      plasma cytokine levels, and intracellular signaling responses in T cells, B
      cells, and monocytes. These antiretroviral therapy-treated HIV-infected
      individuals exhibited a wide range of diversity and divergence in both env and
      pol genes. However, proviral diversity and divergence in env and pol, coreceptor
      tropism, and the level of drug resistance did not significantly correlate with
      markers of immune activation. A clinical history of virologic failure was also
      not significantly associated with levels of immune activation, indicating that a
      history of virologic failure does not inexorably lead to increased immune
      activation as long as suppressive antiretroviral medications are provided.
      Overall, this study demonstrates that latent viral diversity is unlikely to be a
      major driver of persistent HIV-associated immune activation. IMPORTANCE: Chronic
      immune activation, which is associated with cardiovascular disease, neurologic
      disease, and early aging, is likely to be a major driver of morbidity and
      mortality in HIV-infected individuals. Although treatment of HIV with
      antiretroviral medications decreases the level of immune activation, levels do
      not return to normal. The factors driving this persistent immune activation,
      particularly during effective treatment, are poorly understood. In this study, we
      investigated whether characteristics of the latent, integrated HIV provirus that
      persists during treatment are associated with immune activation. We found no
      relationship between latent viral characteristics and immune activation in
      treated individuals, indicating that qualities of the provirus are unlikely to be
      a major driver of persistent inflammation. We also found that individuals who had
      previously failed treatment but were currently effectively treated did not have
      significantly increased levels of immune activation, providing hope that past
      treatment failures do not have a lifelong "legacy" impact.

PMID- 24850731
TI  - Effects of Toll-like receptor stimulation on eosinophilic infiltration in lungs
      of BALB/c mice immunized with UV-inactivated severe acute respiratory syndrome
      related coronavirus vaccine.
AB  - Severe acute respiratory syndrome-related coronavirus (SARS-CoV) is an emerging
      pathogen that causes severe respiratory illness. Whole UV-inactivated SARS-CoV
      (UV-V), bearing multiple epitopes and proteins, is a candidate vaccine against
      this virus. However, whole inactivated SARS vaccine that includes nucleocapsid
      protein is reported to induce eosinophilic infiltration in mouse lungs after
      challenge with live SARS-CoV. In this study, an ability of Toll-like receptor
      (TLR) agonists to reduce the side effects of UV-V vaccination in a 6-month-old
      adult BALB/c mouse model was investigated, using the mouse-passaged Frankfurt 1
      isolate of SARS-CoV. Immunization of adult mice with UV-V, with or without alum,
      resulted in partial protection from lethal doses of SARS-CoV challenge, but
      extensive eosinophil infiltration in the lungs was observed. In contrast, TLR
      agonists added to UV-V vaccine, including lipopolysaccharide, poly(U), and
      poly(I.C) (UV-V+TLR), strikingly reduced excess eosinophilic infiltration in the
      lungs and induced lower levels of interleukin-4 and -13 and eotaxin in the lungs
      than UV-V-immunization alone. Additionally, microarray analysis showed that genes
      associated with chemotaxis, eosinophil migration, eosinophilia, and cell movement
      and the polarization of Th2 cells were upregulated in UV-V-immunized but not in
      UV-V+TLR-immunized mice. In particular, CD11b(+) cells in the lungs of UV-V
      immunized mice showed the upregulation of genes associated with the induction of
      eosinophils after challenge. These findings suggest that vaccine-induced
      eosinophil immunopathology in the lungs upon SARS-CoV infection could be avoided
      by the TLR agonist adjuvants. IMPORTANCE: Inactivated whole severe acute
      respiratory syndrome-related coronavirus (SARS-CoV) vaccines induce neutralizing
      antibodies in mouse models; however, they also cause increased eosinophilic
      immunopathology in the lungs upon SARS-CoV challenge. In this study, the ability
      of adjuvant Toll-like receptor (TLR) agonists to reduce the side effects of UV
      inactivated SARS-CoV vaccination in a BALB/c mouse model was tested, using the
      mouse-passaged Frankfurt 1 isolate of SARS-CoV. We found that TLR stimulation
      reduced the high level of eosinophilic infiltration that occurred in the lungs of
      mice immunized with UV-inactivated SARS-CoV. Microarray analysis revealed that
      genes associated with chemotaxis, eosinophil migration, eosinophilia, and cell
      movement and the polarization of Th2 cells were upregulated in UV-inactivated
      SARS-CoV-immunized mice. This study may be helpful for elucidating the
      pathogenesis underlying eosinophilic infiltration resulting from immunization
      with inactivated vaccine.

PMID- 24850732
TI  - Identification of 10 cowpox virus proteins that are necessary for induction of
      hemorrhagic lesions (red pocks) on chorioallantoic membranes.
AB  - Cowpox viruses (CPXV) cause hemorrhagic lesions ("red pocks") on infected
      chorioallantoic membranes (CAM) of embryonated chicken eggs, while most other
      members of the genus Orthopoxvirus produce nonhemorrhagic lesions ("white
      pocks"). Cytokine response modifier A (CrmA) of CPXV strain Brighton Red (BR) is
      necessary but not sufficient for the induction of red pocks. To identify
      additional viral proteins involved in the induction of hemorrhagic lesions, a
      library of single-gene CPXV knockout mutants was screened. We identified 10
      proteins that are required for the formation of hemorrhagic lesions, which are
      encoded by CPXV060, CPXV064, CPXV068, CPXV069, CPXV074, CPXV136, CPXV168,
      CPXV169, CPXV172, and CPXV199. The genes are the homologues of F12L, F15L, E2L,
      E3L, E8R, A4L, A33R, A34R, A36R, and B5R of vaccinia virus (VACV). Mutants with
      deletions in CPXV060, CPXV168, CPXV169, CPXV172, or CPXV199 induced white pocks
      with a comet-like shape on the CAM. The homologues of these five genes in VACV
      encode proteins that are involved in the production of extracellular enveloped
      viruses (EEV) and the repulsion of superinfecting virions by actin tails. The
      homologue of CPXV068 in VACV is also involved in EEV production but is not
      related to actin tail induction. The other genes encode immunomodulatory proteins
      (CPXV069 and crmA) and viral core proteins (CPXV074 and CPXV136), and the
      function of the product of CPXV064 is unknown. IMPORTANCE: It has been known for
      a long time that cowpox virus induces hemorrhagic lesions on chicken CAM, while
      most of the other orthopoxviruses produce nonhemorrhagic lesions. Although cowpox
      virus CrmA has been proved to be responsible for the hemorrhagic phenotype, other
      proteins causing this phenotype remain unknown. Recently, we generated a complete
      single-gene knockout bacterial artificial chromosome (BAC) library of cowpox
      virus Brighton strain. Out of 183 knockout BAC clones, 109 knockout viruses were
      reconstituted. The knockout library makes possible high-throughput screening for
      studying poxvirus replication and pathogenesis. In this study, we screened all
      109 single-gene knockout viruses and identified 10 proteins necessary for
      inducing hemorrhagic lesions. The identification of these genes gives a new
      perspective for studying the hemorrhagic phenotype and may give a better
      understanding of poxvirus virulence.

PMID- 24850733
TI  - Interaction between hantavirus nucleocapsid protein (N) and RNA-dependent RNA
      polymerase (RdRp) mutants reveals the requirement of an N-RdRp interaction for
      viral RNA synthesis.
AB  - Viral ribonucleocapsids harboring the viral genomic RNA are used as the template
      for viral mRNA synthesis and replication of the viral genome by viral RNA
      dependent RNA polymerase (RdRp). Here we show that hantavirus nucleocapsid
      protein (N protein) interacts with RdRp in virus-infected cells. We mapped the
      RdRp binding domain at the N terminus of N protein. Similarly, the N protein
      binding pocket is located at the C terminus of RdRp. We demonstrate that an N
      protein-RdRp interaction is required for RdRp function during the course of virus
      infection in the host cell. 

PMID- 24850734
TI  - Raman spectroscopic signatures of echovirus 1 uncoating.
AB  - In recent decades, Raman spectroscopy has entered the biological and medical
      fields. It enables nondestructive analysis of structural details at the molecular
      level and has been used to study viruses and their constituents. Here, we used
      Raman spectroscopy to study echovirus 1 (EV1), a small, nonenveloped human
      pathogen, in two different uncoating states induced by heat treatments. Raman
      signals of capsid proteins and RNA genome were observed from the intact virus,
      the uncoating intermediate, and disrupted virions. Transmission electron
      microscopy data revealed general structural changes between the studied
      particles. Compared to spectral characteristics of proteins in the intact virion,
      those of the proteins of the heat-treated particles indicated reduced alpha-helix
      content with respect to beta-sheets and coil structures. Changes observed in
      tryptophan and tyrosine signals suggest an increasingly hydrophilic environment
      around these residues. RNA signals revealed a change in the environment of the
      genome and in its conformation. The ionized-carbonyl vibrations showed small
      changes between the intact virion and the uncoating intermediate, which points to
      cleavage of salt bridges in the protein structure during the uncoating process.
      In conclusion, our data reveal distinguishable Raman signatures of the intact,
      intermediate, and disrupted EV1 particles. These changes indicate structural,
      chemical, and solute-solvent alterations in the genome and in the capsid proteins
      and lay the essential groundwork for investigating the uncoating of EV1 and
      related viruses in real time. IMPORTANCE: In order to combat virus infection, we
      need to know the details of virus uncoating. We present here the novel Raman
      signatures for opened and intact echovirus 1. This gives hope that the signatures
      may be used in the near future to evaluate the ambient conditions in endosomes
      leading to virus uncoating using, e.g., coherent anti-Stokes Raman spectroscopy
      (CARS) imaging. These studies will complement structural studies on virus
      uncoating. In addition, Raman/CARS imaging offers the possibility of making
      dynamic live measurements in vitro and in cells which are impossible to measure
      by, for example, cryo-electron tomography. Furthermore, as viral Raman spectra
      can be overwhelmed with various contaminants, our study is highly relevant in
      demonstrating the importance of sample preparation for Raman spectroscopy in the
      field of virology.

PMID- 24850736
TI  - A single amino acid in EBNA-2 determines superior B lymphoblastoid cell line
      growth maintenance by Epstein-Barr virus type 1 EBNA-2.
AB  - Sequence differences in the EBNA-2 protein mediate the superior ability of type 1
      Epstein-Barr virus (EBV) to transform human B cells into lymphoblastoid cell
      lines compared to that of type 2 EBV. Here we show that changing a single amino
      acid (S442D) from serine in type 2 EBNA-2 to the aspartate found in type 1 EBNA-2
      confers a type 1 growth phenotype in a lymphoblastoid cell line growth
      maintenance assay. This amino acid lies in the transactivation domain of EBNA-2,
      and the S442D change increases activity in a transactivation domain assay. The
      superior growth properties of type 1 EBNA-2 correlate with the greater induction
      of EBV LMP-1 and about 10 cell genes, including CXCR7. In chromatin
      immunoprecipitation assays, type 1 EBNA-2 is shown to associate more strongly
      with EBNA-2 binding sites near the LMP-1 and CXCR7 genes. Unbiased motif
      searching of the EBNA-2 binding regions of the differentially regulated cell
      genes identified an ETS-interferon regulatory factor composite element motif that
      closely corresponds to the sequences known to mediate EBNA-2 regulation of the
      LMP-1 promoter. It appears that the superior induction by type 1 EBNA-2 of the
      cell genes contributing to cell growth is due to their being regulated in a
      manner different from that for most EBNA-2-responsive genes and in a way similar
      to that for the LMP-1 gene. IMPORTANCE: The EBNA-2 transcription factor plays a
      key role in B cell transformation by EBV and defines the two EBV types. Here we
      identify a single amino acid (Ser in type 1 EBV, Asp in type 2 EBV) of EBNA-2
      that determines the superior ability of type 1 EBNA-2 to induce a key group of
      cell genes and the EBV LMP-1 gene, which mediate the growth advantage of B cells
      infected with type 1 EBV. The EBNA-2 binding sites in these cell genes have a
      sequence motif similar to the sequence known to mediate regulation of the EBV LMP
      1 promoter. Further detailed analysis of transactivation and promoter binding
      provides new insight into the physiological regulation of cell genes by EBNA-2.

PMID- 24850735
TI  - Productive replication of human papillomavirus 31 requires DNA repair factor
      Nbs1.
AB  - Activation of the ATM (ataxia telangiectasia-mutated kinase)-dependent DNA damage
      response (DDR) is necessary for productive replication of human papillomavirus 31
      (HPV31). We previously found that DNA repair and homologous recombination (HR)
      factors localize to sites of HPV replication, suggesting that ATM activity is
      required to recruit factors to viral genomes that can productively replicate
      viral DNA in a recombination-dependent manner. The Mre11-Rad50-Nbs1 (MRN) complex
      is an essential component of the DDR that is necessary for ATM-mediated HR repair
      and localizes to HPV DNA foci. In this study, we demonstrate that the HPV E7
      protein is sufficient to increase levels of the MRN complex and also interacts
      with MRN components. We have found that Nbs1 depletion blocks productive viral
      replication and results in decreased localization of Mre11, Rad50, and the
      principal HR factor Rad51 to HPV DNA foci upon differentiation. Nbs1 contributes
      to the DDR by acting as an upstream activator of ATM in response to double-strand
      DNA breaks (DSBs) and as a downstream effector of ATM activity in the intra-S
      phase checkpoint. We have found that phosphorylation of ATM and its downstream
      target Chk2, as well as SMC1 (structural maintenance of chromosome 1), is
      maintained upon Nbs1 knockdown in differentiating cells. Given that ATM and Chk2
      are required for productive replication, our results suggest that Nbs1
      contributes to viral replication outside its role as an ATM activator,
      potentially through ensuring localization of DNA repair factors to viral genomes
      that are necessary for efficient productive replication. IMPORTANCE: The
      mechanisms that regulate human papillomavirus (HPV) replication during the viral
      life cycle are not well understood. Our finding that Nbs1 is necessary for
      productive replication even in the presence of ATM (ataxia telangiectasia-mutated
      kinase) and Chk2 phosphorylation offers evidence that Nbs1 contributes to viral
      replication downstream of facilitating ATM activation. Nbs1 is required for the
      recruitment of Mre11 and Rad50 to viral genomes, suggesting that the MRN complex
      plays a direct role in facilitating productive viral replication, potentially
      through the processing of substrates that are recognized by the key homologous
      recombination (HR) factor Rad51. The discovery that E7 increases levels of MRN
      components, and MRN complex formation, identifies a novel role for E7 in
      facilitating productive replication. Our study not only identifies DNA repair
      factors necessary for HPV replication but also provides a deeper understanding of
      how HPV utilizes the DNA damage response to regulate viral replication.

PMID- 24850737
TI  - Evaluation of the contributions of individual viral genes to newcastle disease
      virus virulence and pathogenesis.
AB  - Naturally occurring Newcastle disease virus (NDV) strains vary greatly in
      virulence. The presence of multibasic residues at the proteolytic cleavage site
      of the fusion (F) protein has been shown to be a primary determinant
      differentiating virulent versus avirulent strains. However, there is wide
      variation in virulence among virulent strains. There also are examples of
      incongruity between cleavage site sequence and virulence. These observations
      suggest that additional viral factors contribute to virulence. In this study, we
      evaluated the contribution of each viral gene to virulence individually and in
      different combinations by exchanging genes between velogenic (highly virulent)
      strain GB Texas (GBT) and mesogenic (moderately virulent) strain Beaudette C
      (BC). These two strains are phylogenetically closely related, and their F
      proteins contain identical cleavage site sequences, (112)RRQKR?F(117). A total of
      20 chimeric viruses were constructed and evaluated in vitro, in 1-day-old chicks,
      and in 2-week-old chickens. The results showed that both the envelope-associated
      and polymerase-associated proteins contribute to the difference in virulence
      between rBC and rGBT, with the envelope-associated proteins playing the greater
      role. The F protein was the major individual contributor and was sometimes
      augmented by the homologous M and HN proteins. The dramatic effect of F was
      independent of its cleavage site sequence since that was identical in the two
      strains. The polymerase L protein was the next major individual contributor and
      was sometimes augmented by the homologous N and P proteins. The leader and
      trailer regions did not appear to contribute to the difference in virulence
      between BC and GBT. IMPORTANCE: This study is the first comprehensive and
      systematic study of NDV virulence and pathogenesis. Genetic exchanges between a
      mesogenic and a velogenic strain revealed that the fusion glycoprotein is the
      major virulence determinant regardless of the identical virulence protease
      cleavage site sequence present in both strains. The contribution of the large
      polymerase protein to NDV virulence is second only to that of the fusion
      glycoprotein. The identification of virulence determinants is of considerable
      importance, because of the potential to generate better live attenuated NDV
      vaccines. It may also be possible to apply these findings to other
      paramyxoviruses.

PMID- 24850738
TI  - Axonal and transynaptic spread of prions.
AB  - Natural transmission of prion diseases depends upon the spread of prions from the
      nervous system to excretory or secretory tissues, but the mechanism of prion
      transport in axons and into peripheral tissue is unresolved. Here, we examined
      the temporal and spatial movement of prions from the brain stem along cranial
      nerves into skeletal muscle as a model of axonal transport and transynaptic
      spread. The disease-specific isoform of the prion protein, PrP(Sc), was observed
      in nerve fibers of the tongue approximately 2 weeks prior to PrP(Sc) deposition
      in skeletal muscle. Initially, PrP(Sc) deposits had a small punctate pattern on
      the edge of muscle cells that colocalized with synaptophysin, a marker for the
      neuromuscular junction (NMJ), in >50% of the cells. At later time points PrP(Sc)
      was widely distributed in muscle cells, but <10% of prion-infected cells
      exhibited PrP(Sc) deposition at the NMJ, suggesting additional prion replication
      and dissemination within muscle cells. In contrast to the NMJ, PrP(Sc) was not
      associated with synaptophysin in nerve fibers but was found to colocalize with
      LAMP-1 and cathepsin D during early stages of axonal spread. We propose that
      PrP(Sc)-bound endosomes can lead to membrane recycling in which PrP(Sc) is
      directed to the synapse, where it either moves across the NMJ into the
      postsynaptic muscle cell or induces PrP(Sc) formation on muscle cells across the
      NMJ. IMPORTANCE: Prion diseases are transmissible and fatal neurodegenerative
      diseases in which prion dissemination to excretory or secretory tissues is
      necessary for natural disease transmission. Despite the importance of this
      pathway, the cellular mechanism of prion transport in axons and into peripheral
      tissue is unresolved. This study demonstrates anterograde spread of prions within
      nerve fibers prior to infection of peripheral synapses (i.e., neuromuscular
      junction) and infection of peripheral tissues (i.e., muscle cells). Within nerve
      fibers prions were associated with the endosomal-lysosomal pathway prior to entry
      into muscle cells. Since early prion spread is anterograde and endosome-lysosomal
      movement within axons is primarily retrograde, these findings suggest that
      endosome-bound prions may have an alternate fate that directs prions to the
      peripheral synapse.

PMID- 24850739
TI  - MDA5 and LGP2: accomplices and antagonists of antiviral signal transduction.
AB  - Mammalian cells have the ability to recognize virus infection and mount a
      powerful antiviral transcriptional response that provides an initial barrier to
      replication and impacts both innate and adaptive immune responses. Retinoic acid
      inducible gene I (RIG-I)-like receptor (RLR) proteins mediate intracellular virus
      recognition and are activated by viral RNA ligands to induce antiviral signal
      transduction. While the mechanisms of RIG-I regulation are already well
      understood, less is known about the more enigmatic melanoma differentiation
      associated 5 (MDA5) and laboratory of genetics and physiology 2 (LGP2). Emerging
      evidence suggests that these two RLRs are intimately associated as both
      accomplices and antagonists of antiviral signal transduction. 

PMID- 24850740
TI  - Genus beta human papillomavirus E6 proteins vary in their effects on the
      transactivation of p53 target genes.
AB  - The genus beta human papillomaviruses (beta HPVs) cause cutaneous lesions and are
      thought to be involved in the initiation of some nonmelanoma skin cancers
      (NMSCs), particularly in patients with the genetic disorder epidermodysplasia
      verruciformis (EV). We have previously reported that at least two of the genus
      beta HPV E6 proteins bind to and/or increase the steady-state levels of p53 in
      squamous epithelial cells. This is in contrast to a well-characterized ability of
      the E6 proteins of cancer-associated HPVs of genus alpha HPV, which inactivate
      p53 by targeting its ubiquitin-mediated proteolysis. In this study, we have
      investigated the ability of genus beta E6 proteins from eight different HPV types
      to block the transactivation of p53 target genes following DNA damage. We find
      that the E6 proteins from diverse beta HPV species and types vary in their
      capacity to block the induction of MDM2, p21, and proapoptotic genes after
      genotoxic stress. We conclude that some genus beta HPV E6 proteins inhibit at
      least some p53 target genes, although perhaps not by the same mechanism or to the
      same degree as the high-risk genus alpha HPV E6 proteins. IMPORTANCE: This study
      addresses the ability of various human papillomavirus E6 proteins to block the
      activation of p53-responsive cellular genes following DNA damage in human
      keratinocytes, the normal host cell for HPVs. The E6 proteins encoded by the high
      risk, cancer-associated HPV types of genus alpha HPV have a well-established
      activity to target p53 degradation and thereby inhibit the response to DNA
      damage. In this study, we have investigated the ability of genus beta HPV E6
      proteins from eight different HPV types to block the ability of p53 to
      transactivate downstream genes following DNA damage. We find that some, but not
      all, genus beta HPV E6 proteins can block the transactivation of some p53 target
      genes. This differential response to DNA damage furthers the understanding of
      cutaneous HPV biology and may help to explain the potential connection between
      some beta HPVs and cancer.

PMID- 24850741
TI  - Phosphoacceptors threonine 162 and serines 170 and 178 within the carboxyl
      terminal RRRS/T motif of the hepatitis B virus core protein make multiple
      contributions to hepatitis B virus replication.
AB  - Phosphorylation of serines 157, 164, and 172 within the carboxyl-terminal SPRRR
      motif of the hepatitis B virus (HBV) core (C) protein modulates HBV replication
      at multiple stages. Threonine 162 and serines 170 and 178, located within the
      carboxyl-terminal conserved RRRS/T motif of HBV C protein, have been proposed to
      be protein kinase A phosphorylation sites. However, in vivo phosphorylation of
      these residues has never been observed, and their contribution to HBV replication
      remains unknown. In this study, [(32)P]orthophosphate labeling of cells
      expressing C proteins followed by immunoprecipitation with anti-HBc antibody
      revealed that threonine 162 and serines 170 and 178 are phosphoacceptor residues.
      A triple-alanine-substituted mutant, mimicking dephosphorylation of all three
      residues, drastically decreased pregenomic RNA (pgRNA) encapsidation, thereby
      decreasing HBV DNA synthesis. In contrast, a triple-glutamate-substituted mutant,
      mimicking phosphorylation of these residues, decreased DNA synthesis without
      significantly decreasing encapsidation. Neither triple mutant affected C protein
      expression or core particle assembly. Individual alanine substitution of
      threonine 162 significantly decreased minus-strand, plus-strand, and relaxed
      circular DNA synthesis, demonstrating that this residue plays multiple roles in
      HBV DNA synthesis. Double-alanine substitution of serines 170 and 178 reduced HBV
      replication at multiple stages, indicating that these residues also contribute to
      HBV replication. Thus, in addition to serines 157, 164, and 172, threonine 162
      and serines 170 and 178 of HBV C protein are also phosphorylated in cells, and
      phosphorylation and dephosphorylation of these residues play multiple roles in
      modulation of HBV replication. IMPORTANCE: Threonine 162, within the carboxyl
      terminal end of the hepatitis B virus (HBV adw) core (C) protein, has long been
      ignored as a phosphoacceptor, even though it is highly conserved among mammalian
      hepadnaviruses and in the overlapping consensus RxxS/T, RRxS/T, and TP motifs.
      Here we show, for the first time, that in addition to the well-known
      phosphoacceptor serines 157, 164, and 172 in SPRRR motifs, threonine 162 and
      serines 170 and 178 in the RRRS/T motif are phosphorylated in cells. We also show
      that, like serines 157, 164, and 172, phosphorylated and dephosphorylated
      threonine 162 and serines 170 and 178 contribute to multiple steps of HBV
      replication, including pgRNA encapsidation, minus-strand and plus-strand DNA
      synthesis, and relaxed-circular DNA synthesis. Of these residues, threonine 162
      is the most important. Furthermore, we show that phosphorylation of C protein is
      required for efficient completion of HBV replication.

PMID- 24850742
TI  - Enhancement of interferon induction by ORF3 product of hepatitis E virus.
AB  - Hepatitis E virus (HEV) causes both the endemic and epidemic spread of acute
      hepatitis in many parts of the world. HEV open reading frame 3 (ORF3) encodes a
      13-kDa multifunctional protein (vp13) that is essential for HEV infection of
      animals. The exact role of vp13 in HEV infection remains unclear. In this study,
      vp13 was found to enhance interferon (IFN) production induced by poly(I . C), a
      synthetic analog of double-stranded RNA. Poly(I . C) treatment induced a higher
      level of IFN-beta mRNA in HeLa cells stably expressing vp13 than in control
      cells. Using a luciferase reporter construct driven by the IFN-beta promoter, we
      demonstrated that vp13 enhanced retinoic acid-inducible gene I (RIG-I)-dependent
      luciferase expression. This enhancement was found to be due to both an increased
      level of RIG-I protein and its activation. The levels of both endogenous and
      exogenous RIG-I were increased by vp13 by extension of the half-life of RIG-I.
      Additionally, vp13 interacts with the RIG-I N-terminal domain and enhances its
      K63-linked ubiquitination, which is essential for RIG-I activation. Analysis of
      vp13 deletion constructs suggested that the C-terminal domain of vp13 was
      essential for the enhancement of RIG-I signaling. In HEV-infected hepatoma cells,
      wild-type HEV led to a higher level of RIG-I and more poly(I . C)-induced IFN
      beta expression than did ORF3-null mutants. Analysis of vp13 from four HEV
      genotypes showed that vp13 from genotype I and III strains boosted RIG-I
      signaling, while vp13 from genotype II and IV strains had a minimal effect. These
      results indicate that vp13 enhances RIG-I signaling, which may play a role in HEV
      invasion. IMPORTANCE: Hepatitis E virus (HEV) is a significant pathogen causing
      hepatitis in many parts of the world, yet it is understudied compared with other
      viral hepatitis pathogens. Here we found that the HEV open reading frame 3
      product, vp13, enhances interferon induction stimulated by a synthetic analog of
      double-stranded RNA. This enhancement may play a role in HEV invasion, as vp13 is
      essential for HEV infection in vivo. The results of this study provide insights
      into virus-cell interactions during HEV infection. In addition to revealing its
      possible roles in HEV interference with cellular signaling, these results suggest
      that the second half of the vp13 sequence can be ligated into the genomes of
      attenuated live viruses to induce an innate immune response for better protective
      immunity, as well as a marker for differentiation of vaccinated animals from
      those infected with the corresponding wild-type viruses.

PMID- 24850743
TI  - Interaction of Kaposi's sarcoma-associated herpesvirus ORF6 protein with single
      stranded DNA.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) ORF6 is homologous to the herpes
      simplex virus 1 (HSV-1) ICP8 and Epstein-Barr virus (EBV) BALF2 proteins. Here,
      we describe its single-stranded DNA (ssDNA) binding properties. Based on previous
      findings with ICP8 and BALF2, a 60-amino-acid C-terminal deletion mutant of Orf6
      was generated, and the protein was purified to explore the function of the C
      terminus in ssDNA binding. We showed that full-length ORF6 binds cooperatively to
      M13 ssDNA, disrupting its secondary structure and extending it to a length
      equivalent to that of duplex M13 DNA. The width of the ORF6-ssDNA filament is 9
      nm, and a 7.3-nm repeat can be distinguished along the filament axis.
      Fluorescence polarization analysis revealed that the wild-type and C-terminal
      mutant ORF6 proteins bind equally well to short ssDNA substrates, with
      dissociation constant (Kd) values of 2.2 * 10(-7)M and 1.5 * 10(-7)M,
      respectively. These values were confirmed by electrophoretic mobility shift assay
      (EMSA) analysis, which also suggested that binding by the full-length protein may
      involve both monomers and small multimers. While no significant difference in
      affinities of binding between full-length ORF6 and the C-terminal deletion mutant
      were observed with the short DNAs, binding of the C-terminal mutant protein to
      M13 ssDNA showed a clear lack of cooperativity as seen by electron microscopy
      (EM). Incubation of a duplex DNA containing a long single-stranded tail with
      double-helical ORF6 protein filaments revealed that the ssDNA segment can be
      enveloped within the protein filament without disrupting the filament structure.
      IMPORTANCE: This work describes the biochemical characterization of the single
      stranded DNA binding protein of KSHV, ORF6, central to viral DNA replication in
      infected cells. A C-terminal deletion mutant protein was generated to aid in
      understanding the role of the C terminus in DNA binding. Here we analyze the
      binding of the wild-type and mutant proteins to short oligomeric and longer
      genomic ssDNA substrates. Although it is capable of interacting with the short
      substrates, the inability of mutant ORF6 to form oligomers in solution hindered
      it from fully covering the long genomic substrates. We previously showed that
      ORF6 forms long filaments in solution, and we showed here that these can absorb
      ssDNA without disruption of the filament structure. This work will provide an
      important basis for future studies by us and/or others.

PMID- 24850744
TI  - Deep sequencing of HIV-infected cells: insights into nascent transcription and
      host-directed therapy.
AB  - Polyadenylated mature mRNAs are the focus of standard transcriptome analyses.
      However, the profiling of nascent transcripts, which often include
      nonpolyadenylated RNAs, can unveil novel insights into transcriptional
      regulation. Here, we separately sequenced total RNAs (Total RNAseq) and mRNAs
      (mRNAseq) from the same HIV-1-infected human CD4(+) T cells. We found that many
      nonpolyadenylated RNAs were differentially expressed upon HIV-1 infection, and we
      identified 8 times more differentially expressed genes at 12 h postinfection by
      Total RNAseq than by mRNAseq. These expression changes were also evident by
      concurrent changes in introns and were recapitulated by later mRNA changes,
      revealing an unexpectedly significant delay between transcriptional initiation
      and mature mRNA production early after HIV-1 infection. We computationally
      derived and validated the underlying regulatory programs, and we predicted drugs
      capable of reversing these HIV-1-induced expression changes followed by
      experimental confirmation. Our results show that combined total and mRNA
      transcriptome analysis is essential for fully capturing the early host response
      to virus infection and provide a framework for identifying candidate drugs for
      host-directed therapy against HIV/AIDS. IMPORTANCE: In this study, we used mass
      sequencing to identify genes differentially expressed in CD4(+) T cells during
      HIV-1 infection. To our surprise, we found many differentially expressed genes
      early after infection by analyzing both newly transcribed unprocessed pre-mRNAs
      and fully processed mRNAs, but not by analyzing mRNAs alone, indicating a
      significant delay between transcription initiation and mRNA production early
      after HIV-1 infection. These results also show that important findings could be
      missed by the standard practice of analyzing mRNAs alone. We then derived the
      regulatory mechanisms driving the observed expression changes using integrative
      computational analyses. Further, we predicted drugs that could reverse the
      observed expression changes induced by HIV-1 infection and showed that one of the
      predicted drugs indeed potently inhibited HIV-1 infection. This shows that it is
      possible to identify candidate drugs for host-directed therapy against HIV/AIDS
      using our genomics-based approach.

PMID- 24850745
TI  - Coexistence of hepatitis B virus quasispecies enhances viral replication and the
      ability to induce host antibody and cellular immune responses.
AB  - Hepatitis B virus (HBV) quasispecies contain a large number of variants that
      serve as a reservoir for viral selection under antiviral treatment and the immune
      response, leading to the acute exacerbation and subsequent development of liver
      failure. However, there is no clear experimental evidence for a significant role
      of HBV quasispecies in viral pathogenesis. In the present study, HBV sequences
      were amplified from a patient with severe liver disease and used for construction
      of HBV replication-competent plasmids. Western blotting, enzyme-linked
      immunosorbent assay (ELISA), and immunofluorescence staining were performed to
      analyze the expression, secretion, and subcellular localization of viral proteins
      in vitro. Viral replication intermediates were detected by Southern blotting. HBV
      gene expression and replication and the induction of specific immune responses in
      an HBV hydrodynamic injection (HI) mouse model were investigated. The results
      demonstrated that two naturally occurring HBV variants, SH and SH-DPS, were
      identified. The variant SH-DPS expressed only a nonexportable hepatitis B virus
      surface antigen (HBsAg) with abnormal intracellular accumulation. The coexistence
      of the HBV variants at a ratio of 1 to 4 (SH to SH-DPS) increased HBV
      replication. Significantly stronger intrahepatic cytotoxic T lymphocyte (CTL)
      responses and antibody responses specific to HBsAg were induced in mice by the
      HBV variants when coapplied by HI. These findings uncovered an unexpected aspect
      of HBV quasispecies: the coexistence of different variants can significantly
      modulate specific host immune responses, representing a novel mechanism for the
      immunopathogenesis of HBV infection. IMPORTANCE: Hepatitis B virus (HBV) is an
      important human pathogen. HBV quasispecies with genetically heterogenous variants
      are thought to play a role in the progression of HBV-associated liver diseases.
      So far, direct evidence is available in only a few cases to confirm the proposed
      role of HBV variants in the pathogenesis. We report here that the coexistence of
      two naturally occurring HBV variants at a ratio of 1 to 4 increased HBV
      replication and induced significantly stronger intrahepatic cytotoxic T
      lymphocyte responses and antibody responses specific to HBV surface antigen
      (HBsAg) in mice. Our discovery uncovered an unexpected aspect of HBV
      quasispecies: the coexistence of different variants can significantly modulate
      specific host immune responses and may enhance immune-mediated liver damage under
      some circumstances, representing a novel mechanism for the immunopathogenesis of
      HBV infection.

PMID- 24850746
TI  - Accelerated, spleen-based titration of variant Creutzfeldt-Jakob disease
      infectivity in transgenic mice expressing human prion protein with sensitivity
      comparable to that of survival time bioassay.
AB  - The dietary exposure of the human population to the prions responsible for the
      bovine spongiform encephalopathy (BSE) epizooty has led to the emergence of
      variant Creutzfeldt-Jakob disease (vCJD). This fatal, untreatable
      neurodegenerative disorder is a growing public health concern because the
      prevalence of the infection seems much greater than the disease incidence and
      because secondary transmission of vCJD by blood transfusion or use of blood
      products has occurred. A current limitation in variant CJD risk assessment is the
      lack of quantitative information on the infectivity of contaminated tissues. To
      address this limitation, we tested the potential of a transgenic mouse line
      overexpressing human prion protein (PrP), which was previously reported to
      propagate vCJD prions. Endpoint titration of vCJD infectivity in different
      tissues was evaluated by two different methods: (i) the "classical" bioassay,
      based on the appearance of clinical symptoms and the detection of pathological
      prion protein in tissues of the inoculated mouse, and (ii) a shortened bioassay
      based on the detection of the protein in the mouse spleen at defined time points.
      The two methods proved equally sensitive in quantifying infectivity, even after
      very-low-dose inoculation of infected material, but the time schedule was
      shortened from ~2.5 years to ~1 year with the spleen bioassay. Compared to the
      "gold-standard" RIII model routinely used for endpoint titration of vCJD/BSE
      prions, either method improved the sensitivity by >2 orders of magnitude and
      allowed reevaluating the infectious titer of spleen from a vCJD individual at
      disease end stage to >1,000-fold-higher values. IMPORTANCE: Here, we provide key
      reevaluation of the infectious titer of variant CJD brain and spleen tissues. The
      highly sensitive, accelerated spleen-based assay should thus constitute a key
      advance for variant CJD epidemiological and risk assessment purposes and should
      greatly facilitate future titration studies, including, for example, those aimed
      at validating decontamination procedures. The overlooked notion that the lymphoid
      tissue exhibits a higher capacity than the brain to replicate prions even after
      low-dose infection raises new questions about the molecular and/or cellular
      determinant(s) involved, a key issue regarding potent silent carriers of variant
      CJD in the lymphoid tissue.

PMID- 24850747
TI  - Discovery and evolution of bunyavirids in arctic phantom midges and ancient
      bunyavirid-like sequences in insect genomes.
AB  - Bunyaviridae is a large family of RNA viruses chiefly comprised of vertebrate and
      plant pathogens. We discovered novel bunyavirids that are approximately equally
      divergent from each of the five known genera. We characterized novel genome
      sequences for two bunyavirids, namely, Kigluaik phantom virus (KIGV), from tundra
      native phantom midges (Chaoborus), and Nome phantom virus (NOMV), from tundra
      invading phantom midges, and demonstrated that these bunyavirid-like sequences
      belong to an infectious virus by passaging KIGV in mosquito cell culture,
      although the infection does not seem to be well sustained beyond a few passages.
      Virus and host gene sequences from individuals collected on opposite ends of
      North America, a region spanning 4,000 km, support a long-term, vertically
      transmitted infection of KIGV in Chaoborus trivittatus. KIGV-like sequences
      ranging from single genes to full genomes are present in transcriptomes and
      genomes of insects belonging to six taxonomic orders, suggesting an ancient
      association of this clade with insect hosts. In Drosophila, endogenous virus
      genes have been coopted, forming an orthologous tandem gene family that has been
      maintained by selection during the radiation of the host genus. Our findings
      indicate that bunyavirid-host interactions in nonbloodsucking arthropods have
      been much more extensive than previously thought. IMPORTANCE: Very little is
      known about the viral diversity in polar freshwater ponds, and perhaps less is
      known about the effects that climate-induced habitat changes in these regions
      will have on virus-host interactions in the coming years. Our results show that
      at the tundra-boreal boundary, a hidden viral landscape is being altered as
      infected boreal phantom midges colonize tundra ponds. Likewise, relatively little
      is known of the deeper evolutionary history of bunyavirids that has led to the
      stark lifestyle contrasts between some genera. The discovery of this novel
      bunyavirid group suggests that ancient and highly divergent bunyavirid lineages
      remain undetected in nature and may offer fresh insight into host reservoirs,
      potential sources of emerging disease, and major lifestyle shifts in the
      evolutionary history of viruses in the family Bunyaviridae.

PMID- 24850750
TI  - Radiation therapy-a double-edged sword?

PMID- 24850751
TI  - Antenatal detection of heritable metabolic disorders.

PMID- 24850748
TI  - Structural insight into BH3 domain binding of vaccinia virus antiapoptotic F1L.
AB  - Apoptosis is a tightly regulated process that plays a crucial role in the removal
      of virus-infected cells, a process controlled by both pro- and antiapoptotic
      members of the Bcl-2 family. The proapoptotic proteins Bak and Bax are regulated
      by antiapoptotic Bcl-2 proteins and are also activated by a subset of proteins
      known as BH3-only proteins that perform dual functions by directly activating Bak
      and Bax or by sequestering and neutralizing antiapoptotic family members.
      Numerous viruses express proteins that prevent premature host cell apoptosis.
      Vaccinia virus encodes F1L, an antiapoptotic protein essential for survival of
      infected cells that bears no discernible sequence homology to mammalian cell
      death inhibitors. Despite the limited sequence similarities, F1L has been shown
      to adopt a novel dimeric Bcl-2-like fold that enables hetero-oligomeric binding
      to both Bak and the proapoptotic BH3-only protein Bim that ultimately prevents
      Bak and Bax homo-oligomerization. However, no structural data on the mode of
      engagement of F1L and its Bcl-2 counterparts are available. Here we solved the
      crystal structures of F1L in complex with two ligands, Bim and Bak. Our
      structures indicate that F1L can engage two BH3 ligands simultaneously via the
      canonical Bcl-2 ligand binding grooves. Furthermore, by structure-guided
      mutagenesis, we generated point mutations within the binding pocket of F1L in
      order to elucidate the residues responsible for both Bim and Bak binding and
      prevention of apoptosis. We propose that the sequestration of Bim by F1L is
      primarily responsible for preventing apoptosis during vaccinia virus infection.
      IMPORTANCE: Numerous viruses have adapted strategies to counteract apoptosis by
      encoding proteins responsible for sequestering proapoptotic components. Vaccinia
      virus, the prototypical member of the family Orthopoxviridae, encodes a protein
      known as F1L that functions to prevent apoptosis by interacting with Bak and the
      BH3-only protein Bim. Despite recent structural advances, little is known
      regarding the mechanics of binding between F1L and the proapoptotic Bcl-2 family
      members. Utilizing three-dimensional structures of F1L bound to host proapoptotic
      proteins, we generated variants of F1L that neutralize Bim and/or Bak. We
      demonstrate that during vaccinia virus infection, engagement of Bim and Bak by
      F1L is crucial for subversion of host cell apoptosis.

PMID- 24850752
TI  - Autism spectrum disorders and hyperactive/impulsive behaviors in Japanese
      patients with Prader-Willi syndrome: a comparison between maternal uniparental
      disomy and deletion cases.
AB  - This study aims to compare maternal uniparental disomy 15 (mUPD) and a paternal
      deletion of 15q11-13 (DEL) of Prader-Willi syndrome (PWS) in regard to autism
      spectrum disorders (ASD). Forty-five Japanese individuals with PWS were recruited
      from a single recruitment center. The participants consisted of 22 children (aged
      from 6 to 12) and 23 adolescents (aged from 13 to 19). Six children and seven
      adolescents were confirmed as having mUPD. Sixteen children and 16 adolescents
      were confirmed as having DEL. Under blindness to the participants' genotypes, a
      single psychologist carried out behavioral and psychological assessments,
      including the Wechsler Intelligence Scales, Pervasive Developmental Disorders
      Autism Society Japan Rating Scale (PARS), and ADHD-Rating Scale-IV (ADHD-RS-IV).
      Two comparisons were made: one between mUPD and DEL children and another between
      mUPD and DEL adolescents. In children, no significant differences were found
      between mUPD and DEL participants in terms of autistic (PARS childhood, P =
      0.657) and impulsive behaviors (ADHD-RS-IV hyperactive/impulsive, P = 0.275). In
      adolescents, mUPD patients showed significantly more autistic symptomatology
      (PARS adolescent, P = 0.027) and significantly more impulsive behavior (ADHD-RS
      IV hyperactive/impulsive, P = 0.01) than DEL patients. Our findings about
      Japanese PWS patients were consistent with previous researches from western
      countries not focused on Asian patients, indicating that mUPD cases would be more
      prone to ASD than DEL cases, regardless of ethnoregional differences. In
      addition, our data suggested that the behavioral difference between mUPD and DEL
      cases in terms of autistic and impulsive symptoms tend to be unrecognizable in
      their childhood.

PMID- 24850753
TI  - Post-antifungal effect and adhesion to buccal epithelial cells of oral Candida
      dubliniensis isolates subsequent to limited exposure to amphotericin B,
      ketoconazole and fluconazole.
AB  - AIM: The post-antifungal effect (PAFE) of Candida and its adherence to oral
      mucosal surfaces are important determinants of candidal pathogenicity. Candida
      dubliniensis is allied with recurrent oral candidosis. Oral candidosis can be
      treated with amphotericin B, ketoconazole and fluconazole. There is no
      information on the PAFE and its impact on adhesion to oral buccal epithelial
      cells (BEC) of oral C. dubliniensis isolates. Therefore, the main objective was
      to reconnoiter the PAFE and adhesion to BEC of 20 C. dubliniensis isolates
      following brief exposure to aforementioned antimycotics. METHODS: After
      determining the minimum inhibitory concentration (MIC), C. dubliniensis isolates
      were exposed to sub-lethal concentrations of these drugs for 1 h. Following
      subsequent drug removal, the PAFE and adhesion to BEC, was determined by a
      turbidometric method, and an adhesion assay, respectively. RESULTS: Minimum
      inhibitory concentration (MUg/mL) to amphotericin B, ketoconazole and
      fluconazole, ranged from 0.002 to 0.125, 0.002 to 0.012 and 0.016 to 0.38,
      respectively. Amphotericin B and ketoconazole induced mean PAFE (hours) were 2.21
      and 0.6, respectively. Fluconazole failed to produce a detectable PAFE. Compared
      to controls, amphotericin B, ketoconazole and fluconazole suppressed the ability
      to adhere to BEC with a mean percentage reduction of 74.31%, 49.80% (P < 0.0001)
      and 29.36% (P < 0.05), respectively. CONCLUSIONS: Brief exposure to sub-lethal
      concentrations of aforementioned drugs would exert an antifungal effect by
      modifying the growth and adhesion of C. dubliniensis isolates.

PMID- 24850754
TI  - Erythropoietin therapy after allogeneic hematopoietic cell transplantation: a
      prospective, randomized trial.
AB  - We conducted a prospective randomized trial to assess hemoglobin (Hb) response to
      recombinant human erythropoietin (rhEPO) therapy after hematopoietic cell
      transplantation (HCT). Patients (N = 131) were randomized (1:1) between no
      treatment (control arm) or erythropoietin at 500 U/kg per week (EPO arm).
      Patients were also stratified into 3 cohorts: patients undergoing myeloablative
      HCT with rhEPO to start on day (D)28, patients given nonmyeloablative HCT (NMHCT)
      with rhEPO to start on D28, and patients also given NMHCT but with rhEPO to start
      on D0. The proportion of complete correctors (ie, Hb >=13 g/dL) before D126
      posttransplant was 8.1% in the control arm (median not reached) and 63.1% in the
      EPO arm (median, 90 days) (P < .001). Hb levels were higher and transfusion
      requirements decreased (P < .001) in the EPO arm, but not during the first month
      in the nonmyeloablative cohort starting rhEPO on D0. There was no difference in
      rates of thromboembolic events or other complications between the 2 arms. This is
      the first randomized trial to demonstrate that rhEPO therapy hastens erythroid
      recovery and decreases transfusion requirements when started one month after
      allogeneic HCT. There was no benefit to start rhEPO earlier after NMHCT. 

PMID- 24850755
TI  - Interaction of TIF-90 and filamin A in the regulation of rRNA synthesis in
      leukemic cells.
AB  - The transcription initiation factor I (TIF-IA) is an important regulator of the
      synthesis of ribosomal RNA (rRNA) through its facilitation of the recruitment of
      RNA polymerase I (Pol I) to the ribosomal DNA promoter. Activation of the
      phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway, which occurs
      commonly in acute myelogenous leukemia, enhances rRNA synthesis through TIF-IA
      stabilization and phosphorylation. We have discovered that TIF-IA coexists with a
      splicing isoform, TIF-90, which is expressed preferentially in the nucleolus and
      at higher levels in proliferating and transformed hematopoietic cells. TIF-90
      interacts directly with Pol I to increase rRNA synthesis as a consequence of Akt
      activation. Furthermore, TIF-90 binds preferentially to a 90-kDa cleavage product
      of the actin binding protein filamin A (FLNA) that inhibits rRNA synthesis.
      Increased expression of TIF-90 overcomes the inhibitory effect of this cleavage
      product and stimulates rRNA synthesis. Because activated Akt also reduces FLNA
      cleavage, these results indicate that activated Akt and TIF-90 function in
      parallel to increase rRNA synthesis and, as a consequence, cell proliferation in
      leukemic cells. These results provide evidence that the direct targeting of Akt
      would be an effective therapy in acute leukemias in which Akt is activated. 

PMID- 24850757
TI  - miR-217 is an oncogene that enhances the germinal center reaction.
AB  - microRNAs are a class of regulators of gene expression that have been shown
      critical for a great number of biological processes; however, little is known of
      their role in germinal center (GC) B cells. Although the GC reaction is crucial
      to ensure a competent immune response, GC B cells are also the origin of most
      human lymphomas, presumably due to bystander effects of the immunoglobulin gene
      remodeling that takes place at these sites. Here we report that miR-217 is
      specifically upregulated in GC B cells. Gain- and loss-of-function mouse models
      reveal that miR-217 is a positive modulator of the GC response that increases the
      generation of class-switched antibodies and the frequency of somatic
      hypermutation. We find that miR-217 down-regulates the expression of a DNA damage
      response and repair gene network and in turn stabilizes Bcl-6 expression in GC B
      cells. Importantly, miR-217 overexpression also promotes mature B-cell
      lymphomagenesis; this is physiologically relevant as we find that miR-217 is
      overexpressed in aggressive human B-cell lymphomas. Therefore, miR-217 provides a
      novel molecular link between the normal GC response and B-cell transformation. 

PMID- 24850756
TI  - Consensus guidelines for the diagnosis and clinical management of Erdheim-Chester
      disease.
AB  - Erdheim-Chester disease (ECD) is a rare, non-Langerhans histiocytosis. Recent
      findings suggest that ECD is a clonal disorder, marked by recurrent BRAFV600E
      mutations in >50% of patients, in which chronic uncontrolled inflammation is an
      important mediator of disease pathogenesis. Although ~500 to 550 cases have been
      described in the literature to date, increased physician awareness has driven a
      dramatic increase in ECD diagnoses over the last decade. ECD frequently involves
      multiple organ systems and has historically lacked effective therapies. Given the
      protean clinical manifestations and the lack of a consensus-derived approach for
      the management of ECD, we provide here the first multidisciplinary consensus
      guidelines for the clinical management of ECD. These recommendations were
      outlined at the First International Medical Symposium for ECD, comprised of a
      comprehensive group of international academicians with expertise in the
      pathophysiology and therapy of ECD. Detailed recommendations on the initial
      clinical, laboratory, and radiographic assessment of ECD patients are presented
      in addition to treatment recommendations based on critical appraisal of the
      literature and clinical experience. These formalized consensus descriptions will
      hopefully facilitate ongoing and future research efforts in this disorder. 

PMID- 24850758
TI  - CBFbeta and RUNX1 are required at 2 different steps during the development of
      hematopoietic stem cells in zebrafish.
AB  - CBFbeta and RUNX1 form a DNA-binding heterodimer and are both required for
      hematopoietic stem cell (HSC) generation in mice. However, the exact role of
      CBFbeta in the production of HSCs remains unclear. Here, we generated and
      characterized 2 zebrafish cbfb null mutants. The cbfb(-/-) embryos underwent
      primitive hematopoiesis and developed transient erythromyeloid progenitors, but
      they lacked definitive hematopoiesis. Unlike runx1 mutants, in which HSCs are not
      formed, nascent, runx1(+)/c-myb(+) HSCs were formed in cbfb(-/-) embryos.
      However, the nascent HSCs were not released from the aorta-gonad-mesonephros
      (AGM) region, as evidenced by the accumulation of runx1(+) cells in the AGM that
      could not enter circulation. Moreover, wild-type embryos treated with an
      inhibitor of RUNX1-CBFbeta interaction, Ro5-3335, phenocopied the hematopoietic
      defects in cbfb(-/-) mutants, rather than those in runx1(-/-) mutants. Finally,
      we found that cbfb was downstream of the Notch pathway during HSC development.
      Our data suggest that runx1 and cbfb are required at 2 different steps during
      early HSC development. CBFbeta is not required for nascent HSC emergence but is
      required for the release of HSCs from AGM into circulation. Our results also
      indicate that RUNX1 can drive the emergence of nascent HSCs in the AGM without
      its heterodimeric partner CBFbeta. 

PMID- 24850759
TI  - In vivo time-lapse imaging shows diverse niche engagement by quiescent and
      naturally activated hematopoietic stem cells.
AB  - Hematopoietic stem cells (HSCs) maintain the turnover of mature blood cells
      during steady state and in response to systemic perturbations such as infections.
      Their function critically depends on complex signal exchanges with the bone
      marrow (BM) microenvironment in which they reside, but the cellular mechanisms
      involved in HSC-niche interactions and regulating HSC function in vivo remain
      elusive. We used a natural mouse parasite, Trichinella spiralis, and multipoint
      intravital time-lapse confocal microscopy of mouse calvarium BM to test whether
      HSC-niche interactions may change when hematopoiesis is perturbed. We find that
      steady-state HSCs stably engage confined niches in the BM whereas HSCs harvested
      during acute infection are motile and therefore interact with larger niches.
      These changes are accompanied by increased long-term repopulation ability and
      expression of CD44 and CXCR4. Administration of a CXCR4 antagonist affects the
      duration of HSC-niche interactions. These findings suggest that HSC-niche
      interactions may be modulated during infection. 

PMID- 24850760
TI  - CLL-cells induce IDOhi CD14+HLA-DRlo myeloid-derived suppressor cells that
      inhibit T-cell responses and promote TRegs.
AB  - Myeloid-derived suppressor cells (MDSCs) represent a heterogeneous population
      that shares certain characteristics including an aberrant myeloid phenotype and
      the ability to suppress T cells. MDSCs have been predominantly studied in
      malignant diseases and findings suggest involvement in tumor-associated immune
      suppression. Chronic lymphocytic leukemia (CLL) is the leukemia with the highest
      incidence among adults. Immune defects occur already at early disease stages and
      impact the clinical course. We assessed presence, frequency, association to other
      immune parameters, and functional properties of circulating CD14(+) cells lacking
      HLA-DR expression (HLA-DR(lo)) in patients with untreated CLL. These monocytic
      cells represent one of the best-defined human MDSC subsets. Frequency of
      CD14(+)HLA-DR(lo) cells was significantly increased in CLL patients. Furthermore,
      MDSCs suppressed in vitro T-cell activation and induced suppressive regulatory T
      cells (TRegs). The MDSC-mediated modulation of T cells could be attributed to
      their increased indoleamine 2,3-dioxygenase (IDO) activity. CLL cells induced
      IDO(hi) MDSCs from healthy donor monocytes suggesting bidirectional crosstalk
      between CLL-cells, MDSCs, and TRegs. Overall, we identified a MDSC population
      that expands in CLL. The exact mechanisms responsible for such accumulation
      remain to be elucidated and it will be of interest to test whether antagonizing
      suppressive functions of CLL MDSCs could represent a mean for enhancing immune
      responses. 

PMID- 24850761
TI  - A von Willebrand factor fragment containing the D'D3 domains is sufficient to
      stabilize coagulation factor VIII in mice.
AB  - Plasma factor VIII (FVIII) and von Willebrand factor (VWF) circulate together as
      a complex. We identify VWF fragments sufficient for FVIII stabilization in vivo
      and show that hepatic expression of the VWF D'D3 domains (S764-P1247), either as
      a monomer or a dimer, is sufficient to raise FVIII levels in Vwf(-/-) mice from a
      baseline of ~5% to 10%, to ~50% to 100%. These results demonstrate that a
      fragment containing only ~20% of the VWF sequence is sufficient to support FVIII
      stability in vivo. Expression of the VWF D'D3 fragment fused at its C terminus to
      the Fc segment of immunoglobulin G1 results in markedly enhanced survival in the
      circulation (t1/2 > 7 days), concomitant with elevated plasma FVIII levels (>25%
      at 7 days) in Vwf(-/-) mice. Although the VWF D'D3-Fc chimera also exhibits
      markedly prolonged survival when transfused into FVIII-deficient mice, the
      cotransfused FVIII is rapidly cleared. Kinetic binding studies show that VWF
      propeptide processing of VWF D'D3 fragments is required for optimal FVIII
      affinity. The reduced affinity of VWF D'D3 and VWF D'D3-Fc for FVIII suggests
      that the shortened FVIII survival in FVIII-deficient mice transfused with FVIII
      and VWF D'D3/D'D3-Fc is due to ineffective competition of these fragments with
      endogenous VWF for FVIII binding. 

PMID- 24850762
TI  - Personality profiles and psychopathology among students exposed to dating
      violence at theObafemi AwolowoUniversity, Ile-Ife.
AB  - Dating violence is a complex phenomenon, and researchers continue to examine a
      wide range of precursors and contributing factors. Evidence indicates that
      violent intimate partners may be more likely to have personality disorders and
      dependency and attachment problems compared with non-violent ones. The aim of the
      present study is to evaluate the interaction between the personality profiles,
      pattern of psychopathology, and dating violence among university students in
      Obafemi Awolowo University, Ile-Ife. The study utilized a cross-sectional survey
      design with a total of 400 students selected using a multistage sampling
      technique. They completed the Sociodemographic Data Schedule, the Conflict Tactic
      Scale (CTS), Eysenck Personality Questionnaire (EPQ), and the General Health
      Questionnaire (GHQ). Univariate analysis was used to determine the prevalence of
      dating violence, psychopathology, and personality traits, and these were
      expressed in percentages. Association at bivariate level was assessed using chi
      square and at multivariate level using logistic regression and correlations as
      was appropriate depending on the type of variable. The age of the respondents
      ranged between 18 and 35 years (M = 21.44, SD = 2.99). The prevalence of dating
      violence in the previous 12 months was 34%, and the prevalence of psychopathology
      was 15%. In the logistic regression model constructed, it was found that the
      significant predictors of dating violence were the psychoticism and neuroticism
      personality traits, which were also found to be positive correlates of
      psychopathology. The magnitude of dating violence found in this study is
      comparable with those found in other countries of the world. This study found an
      association between dating violence and personality in the study population and
      also between certain personality traits and psychopathology. The personality
      profiles of students could affect their interpersonal relationships greatly, and
      this fact must feature in dating violence prevention programs. 

PMID- 24850763
TI  - Encouraging responses in sexual and relationship violence prevention: what
      program effects remain 1 year later?
AB  - Colleges and universities are high-risk settings for sexual and relationship
      violence. To address these problems, institutions of higher education have
      implemented prevention programs, many of which train students as potential
      bystanders who can step in to help diffuse risky situations, identify and
      challenge perpetrators, and assist victims. The impact of bystander sexual and
      relationship violence prevention programs on long-term behavior of bystanders has
      remained a key unanswered question for those who seek to offer the most effective
      programs as well as for policy makers. In this study, the researchers
      experimentally evaluated the effectiveness of the Bringing in the Bystander(r) in
      person program. Participants were 948 1st-year college students of whom 47.8%
      were women and 85.2% identified as White (15% also identified as Hispanic in a
      separate question) between the ages of 18 and 24 at two universities (one a
      rural, primarily residential campus and the other an urban, highly commuter
      campus) in the northeastern United States. To date, this is the first study to
      have found positive behavior changes as long-lasting as 1 year following an
      educational workshop focusing on engaging bystanders in preventing sexual and
      relationship violence. Even so, many questions remain to be answered about
      prevention and intervention of this type. More prospective research is needed on
      bystander-focused prevention of these forms of violence to help understand and
      better predict the complicated relationships both between and among the attitudes
      and behaviors related to preventing sexual and relationship violence. In this
      regard, we make specific recommendations for designing and evaluating programs
      based on our findings relating to the importance of moderators, especially two
      key understudied ones, readiness to help and opportunity to intervene. 

PMID- 24850764
TI  - Child maltreatment and educational attainment in young adulthood: results from
      the Ontario Child Health Study.
AB  - There is increasing evidence for the adverse effects of child maltreatment on
      academic performance; however, most of these studies used selective samples and
      did not account for potential confounding or mediating factors. We examined the
      relationship between child physical abuse (PA; severe and non-severe) and sexual
      abuse (SA) and educational attainment (years of education, failure to graduate
      from high school) with a Canadian community sample. We used data from the Ontario
      Child Health Study (N = 1,893), a province-wide longitudinal survey. Potential
      confounding variables (family socio-demographic and parental capacity) and child
      level characteristics were assessed in 1983, and child abuse was determined in
      2000-2001 based on retrospective self-report. Results showed that PA and SA were
      associated with several factors indicative of social disadvantage in childhood.
      Multilevel regression analyses for years of education revealed a significant
      estimate for severe PA based on the unadjusted model (-0.60 years, 95% CI = [
      0.45, -0.76]); estimates for non-severe PA (0.05 years, CI = [-0.15, 0.26]) and
      SA (-0.25 years, CI = [-0.09, -0.42]) were not significant. In the adjusted full
      model, the only association to reach significance was between severe PA and
      reduced years of education (-0.31 years, CI = [-0.18, -0.44]). Multilevel
      regression analyses for failure to graduate from high school showed significant
      unadjusted estimates for severe PA (OR = 1.77, 95% CI = [1.21, 2.58]) and non
      severe PA (OR = 1.61, CI = [1.01, 2.57]); SA was not associated with this outcome
      (OR = 1.40, CI = [0.94, 2.07]). In the adjusted full models, there were no
      significant associations between child abuse variables and failure to graduate.
      The magnitude of effect of PA on both outcomes was reduced largely by child
      individual characteristics. These findings generally support earlier research,
      indicating the adverse effects of child maltreatment on educational attainment.
      Of particular note, severe PA was associated with reduced years of education
      after accounting for a comprehensive set of potential confounding variables and
      child characteristics. 

PMID- 24850765
TI  - Posttraumatic growth in survivors of intimate partner violence: an assumptive
      world process.
AB  - Adverse consequences of intimate partner violence (IPV) are well documented,
      whereas less research has explored positive changes. Recent efforts indicate that
      survivors report posttraumatic growth (PTG), but the schema reconstruction
      hypothesis by which this is achieved is in need of further investigation. One
      model of PTG suggests that growth is triggered by trauma(s) that challenges an
      individual's assumptive world. This threat promotes cognitive processing and
      schema reconstruction that fosters a sense of meaning and value in one's life. As
      schema change is posited as the main cognitive antecedent of PTG, a longitudinal
      assessment of world assumptions was used to examine whether assumption change
      predicts PTG in IPV survivors. Results indicate that world assumptions became
      more positive 1 year after an initial interview but only for women who had not
      been revictimized in the year between study assessments. Furthermore, positive
      world assumption change was associated with greater PTG scores. Implications for
      intervention and research are discussed. 

PMID- 24850769
TI  - Diphenylhydantoin ginggival hyperplasia.

PMID- 24850766
TI  - Heterogeneity of relationally aggressive adolescents in Taiwan: direct and
      indirect relational aggression.
AB  - Relational aggressors mistreat their targets in covert ways; however, they also
      inflict psychological harm to victims. A clarification of the distinctive
      function of the perpetrators' destructive patterns would be helpful for
      interventional consideration. This study's purpose was to, first, explore the
      classification of relational aggression (RA) by means of operational channels,
      and then, to examine the psychosocial characteristics of each subtype. The
      participants were 860 junior high school students (431 boys, M age = 14.2) from
      four schools in Taiwan. Self-reported measures of empathy, normative beliefs of
      RA, and coping strategy of interpersonal conflicts were used for data collection,
      as well as peer-nominated measures of RA and peer acceptance. By means of cluster
      analyses, five clusters were identified: direct, indirect, severe/combined,
      mild/combined, and uninvolved. The meaningfulness of the resultant cluster
      solution was examined through the analysis of social-cognitive, affective, and
      behavioral features as well as psychosocial adjustment. The findings indicated
      that different subgroups of relational aggressors demonstrated distinct
      psychosocial characteristics. In particular, in contrast to non-involved
      adolescents, the direct group tended to regard RA as acceptable, and the indirect
      group was more likely to rely on social support and have negative emotional
      reactions in dealing with interpersonal problems. 

PMID- 24850771
TI  - Wound healing of osteotomy defects prepared with piezo or conventional surgical
      instruments: a pilot study in rabbits.
AB  - AIM: The aim of the present study was to evaluate and compare the wound-healing
      process following osteotomies performed with either conventional rotary burs or
      piezoelectric surgery in a rabbit model. METHODS: Two types of osteotomy window
      defects of the nasal cavities were prepared on the nasal bone of 16 adult New
      Zealand white rabbits with either a conventional rotary bur or piezo surgery. The
      defects were covered with a resorbable membrane. Four animals were killed at 1,
      2, 3, and 5 weeks after the surgical procedure, respectively. Histological and
      morphometric evaluations were performed to assess the volumetric density of
      various tissue components: the blood clot, vascularized structures, provisional
      matrix, osteoid, mineralized bone, bone debris, residual tissue, and old bone.
      RESULTS: Significantly more bone debris was found at 1 week in the conventionally
      prepared defects compared to the piezo surgically-prepared defects. At 2 and 3
      weeks, a newly-formed hard tissue bridge, mainly composed of woven bone, was
      seen; however, no statistically-significant differences were observed. At 5
      weeks, the defects were completely filled with newly-formed bone. CONCLUSION: The
      defects prepared by piezo surgery showed a significantly decreased proportion of
      bone debris at 1 week, compared to conventional rotary bur defect.

PMID- 24850773
TI  - The good, the bad, and the ugly of interleukin-6 signaling.

PMID- 24850774
TI  - Novel iron oxyhydroxide lepidocrocite nanosheet as ultrahigh power density anode
      material for asymmetric supercapacitors.
AB  - A simple one-step electroplating route is proposed for the synthesis of novel
      iron oxyhydroxide lepidocrocite (gamma-FeOOH) nanosheet anodes with distinct
      layered channels, and the microstructural influence on the pseudocapacitive
      performance of the obtained gamma-FeOOH nanosheets is investigated via in situ X
      ray absorption spectroscopy (XAS) and electrochemical measurement. The in situ
      XAS results regarding charge storage mechanisms of electrodeposited gamma-FeOOH
      nanosheets show that a Li(+) can reversibly insert/desert into/from the 2D
      channels between the [FeO6 ] octahedral subunits depending on the applied
      potential. This process charge compensates the Fe(2+) /Fe(3+) redox transition
      upon charging-discharging and thus contributes to an ideal pseudocapacitive
      behavior of the gamma-FeOOH electrode. Electrochemical results indicate that the
      gamma-FeOOH nanosheet shows the outstanding pseudocapacitive performance, which
      achieves the extraordinary power density of 9000 W kg(-1) with good rate
      performance. Most importantly, the asymmetric supercapacitors with excellent
      electrochemical performance are further realized by using 2D MnO2 and gamma-FeOOH
      nanosheets as cathode and anode materials, respectively. The obtained device can
      be cycled reversibly at a maximum cell voltage of 1.85 V in a mild aqueous
      electrolyte, further delivering a maximum power density of 16 000 W kg(-1) at an
      energy density of 37.4 Wh kg(-1).

PMID- 24850775
TI  - Bacterial comparison of preoperative rinsing and swabbing for oral surgery using
      0.2% chlorhexidine.
AB  - AIM: The aim of the present study was to compare bacterial load using
      preoperative rinsing and swabbing techniques for oral surgery with 0.2%
      chlorhexidine (CHX). METHODS: Participants were healthy volunteers undergoing a
      general anesthetic for the removal of teeth. Participants were randomly allocated
      to receive 15 mL of 0.2% CHX for 60 s as either a rinse or have their mouths
      swabbed. Plaque samples were aseptically collected pre- and post-rinsing from the
      same sites in all patients (the distal surface of all second molar teeth).
      RESULTS: Patients in the swab group had similar bacteria counts before and after
      the application of CHX (143.4 vs 138.5 colonies, P = 1.000). After rinsing with
      CHX, there was an eightfold reduction of bacterial load (71 vs 8.8 colonies, P <
      0.001). CONCLUSION: The present study demonstrates that the use of CHX as an
      antimicrobial agent is effective in reducing the overall number of bacterial
      colonies in the oral cavity. Rinsing is a more effective method of doing this.

PMID- 24850776
TI  - European drug agency backtracks on plan to give researchers access to clinical
      trial reports.

PMID- 24850777
TI  - MBL2 gene variants coding for mannose-binding lectin deficiency are associated
      with increased risk of nephritis in Danish patients with systemic lupus
      erythematosus.
AB  - OBJECTIVES: Autoimmunity may in part result from deficiencies in the processing
      of apoptotic debris. As mannose-binding lectin (MBL) is involved in such
      processes, we hypothesized that the variants in the MBL2 gene resulting in MBL
      deficiency confer an increased risk of nephritis in systemic lupus erythematosus
      (SLE). METHODS: A total of 171 SLE patients attending a Danish tertiary
      rheumatology referral center were included. Common variant alleles in exon 1 of
      the MBL2 gene (R52C, rs5030737; G54D, rs1800450; G57E, rs1800451) were genotyped.
      The normal allele and variant alleles are termed A and O, respectively. The
      follow-up period was defined as the time from fulfillment of the ACR 1987
      classification criteria for SLE until the occurrence of an event (nephritis, end
      stage renal disease (ESRD), or death) or end of follow-up. Cox regression
      analyses were controlled for gender, age and race. RESULTS: During a median
      follow-up of 5.7 years, nephritis developed in 94 patients, and ESRD developed in
      16 of these patients. Twenty-seven patients died. The distribution of the MBL2
      genotypes A/A, A/O and O/O was 58%, 35% and 7.0%, respectively. Compared to the
      rest, O/O patients had 2.6 times (95% CI: 1.2-5.5) higher risk of developing
      nephritis, and their risk of death after 10 years was 6.0 times increased (95%
      CI: 1.0-36). MBL serum levels below 100 ng/ml were associated with a 2.0 (95% CI:
      1.2-3.4; p = 0.007) increased risk of developing nephritis. ESRD and histological
      class of nephritis were not associated with MBL deficiency. CONCLUSIONS:
      Genetically determined MBL deficiency was associated with development of
      nephritis in SLE patients, but not with histological class of nephritis or ESRD.

PMID- 24850778
TI  - Do difficulties in accessing in-hours primary care predict higher use of out-of
      hours GP services? Evidence from an English National Patient Survey.
AB  - INTRODUCTION: It is believed that some patients are more likely to use out-of
      hours primary care services because of difficulties in accessing in-hours care,
      but substantial evidence about any such association is missing. METHODS: We
      analysed data from 567,049 respondents to the 2011/2012 English General Practice
      Patient Survey who reported at least one in-hours primary care consultation in
      the preceding 6 months. Of those respondents, 7% also reported using out-of-hours
      primary care. We used logistic regression to explore associations between use of
      out-of-hours primary care and five measures of in-hours access (ease of getting
      through on the telephone, ability to see a preferred general practitioner,
      ability to get an urgent or routine appointment and convenience of opening
      hours). We illustrated the potential for reduction in use of out-of-hours primary
      care in a model where access to in-hours care was made optimal. RESULTS: Worse in
      hours access was associated with greater use of out-of-hours primary care for
      each access factor. In multivariable analysis adjusting for access and patient
      characteristic variables, worse access was independently associated with
      increased out-of-hours use for all measures except ease of telephone access.
      Assuming these associations were causal, we estimated that an 11% relative
      reduction in use of out-of-hours primary care services in England could be
      achievable if access to in-hours care were optimal. CONCLUSIONS: This secondary
      quantitative analysis provides evidence for an association between difficulty in
      accessing in-hours care and use of out-of-hours primary care services. The
      findings can motivate the development of interventions to improve in-hour access.

PMID- 24850779
TI  - Analysis of salivary secretor status in patients with oral submucous fibrosis: a
      case-control study.
AB  - AIM: Many individuals have various tobacco-related habits, yet only some develop
      clinical manifestation of lesions. This raises the question of whether there any
      inherent or host risk factors involved in the pathogenesis which need to be
      further investigated. The aim of the present study was to analyze the ABO
      antigen, secretor status, and blood groups of patients. METHODS: The study
      consisted of 99 participants, with 33 patients allocated to three groups: (a)
      patients with a tobacco-related habit and oral submucous fibrosis (OSF); (b)
      patients with a tobacco-related habit, but no lesions; and (c) healthy controls.
      A total of 1 mL unstimulated saliva was collected in a sterile test tube, and the
      Wiener agglutination test was performed to analyze the ABO antigen in all three
      groups. RESULTS: All of the OSF patients were non-secretors, whereas 84.8% were
      non-secretors in the group of individuals with habits as compared to 15.2% in the
      healthy group. A statistically-significant difference was observed between the
      OSF and healthy groups. The patients in the OSF group were predominantly blood
      group A, followed by groups O, B, and AB. CONCLUSION: There is a correlation
      between salivary secretor status and the development of OSF. Thus, non-secretors
      are at greater risk of and more prone to the development of oral lesions. Blood
      groups A and O predominate over the B and AB blood groups.

PMID- 24850780
TI  - E-cigarettes work better than nicotine replacement and willpower to help people
      quit smoking.

PMID- 24850781
TI  - Voice Outcome of Modified Frontolateral Partial Laryngectomy in Excised Canine
      Larynges and Finite Element Model.
AB  - OBJECTIVE: To evaluate vocal parameters after modified frontolateral partial
      laryngectomy (MFLPL) and frontolateral partial laryngectomy (FLPL) in both
      excised canine and finite element models. STUDY DESIGN: FLPL and MFLPL were
      compared, using a prospective paired case control laboratory study with excised
      canine larynx and computational modeling. SETTING: Basic science study conducted
      in university laboratory. METHODS: FLPL and MFLPL were performed serially on 9
      excised canine larynges. The excised larynx bench apparatus was used to collect
      phonation threshold pressure (PTP) and high-speed video data. A finite element
      model was built to compare a normal vocal fold with applied tension, a cut fold
      with no applied tension (simulating FLPL), and a cut fold with applied tension
      (simulating MFLPL). Stress values and distributions across the 3 conditions were
      computed. RESULTS: The mean PTP increase after MFLPL (15.45-17.46 cmH2O) was not
      statistically significant. In the excised canine model, fundamental frequency
      (F0) showed a significant increase for the MFLPL (P = .039). Differences in
      vibration amplitudes were not statistically significant. Von Mises stress
      distribution was most similar between the MFLPL model and the normal fold.
      Maximum von Mises stresses at the midline were 17.56, 21.63, and 5.10 kPa for the
      normal, MFLPL, and FLPL, respectively, and 47.57, 63.98, and 101.97 kPa at the
      peripheries. CONCLUSIONS: From these results, we conclude that MFLPL has the
      potential to give a better voice outcome while avoiding tracheotomy in partial
      laryngectomy patients. In vivo study in canines to examine the healing process
      would lend further evidence-based support for this surgical method.

PMID- 24850782
TI  - Orofacial adverse effects of biological agents.
AB  - Biological agents (BA) are increasingly used effectively in the treatment of a
      range of disorders, but to date, their application in diseases affecting the
      orofacial region has been fairly limited. Several orofacial adverse effects
      related to BA have been recently reported. However, the evidence for such adverse
      reactions is not always strong, and some of the adverse effects of BA have only
      been reported in case reports or case series. Most reactions to BA reported thus
      far have been in association with antitumor necrosis factor-alpha agents, which
      is not surprising, as these are the most widely-used BA. In the present study,
      the orofacial adverse effects are reported with various BA in order to sensitize
      clinicians to the possibilities. In addition, we briefly summarize the mode of
      action and indications of these BA. As the use and range of BA increases, the
      number and diversity of adverse effects might well increase. Despite the adverse
      effects of biological agents, these may often be less serious than the adverse
      effects of the more traditional immunosuppressive agents. 

PMID- 24850783
TI  - Youth exposure to alcohol advertising on television in the UK, the Netherlands
      and Germany.
AB  - BACKGROUND: Exposure of young people to alcohol advertising is a risk factor for
      underage drinking. This study assessed youth exposure to television alcohol
      advertising in the UK, the Netherlands and Germany, from December 2010 to May
      2011. METHODS: A negative binomial regression model predicted number of alcohol
      advertisements from the proportion of the television viewership in each age
      group. This allowed comparison of alcohol advertisement incidence for each youth
      age category relative to an adult reference category. RESULTS: In the UK, those
      aged 10-15 years were significantly more exposed to alcohol advertisements per
      viewing hour than adults aged >= 25 years [incidence rate ratio (IRR) = 1.11; 95%
      confidence interval (95% CI): 1.06, 1.18; P < 0.01]; in the Netherlands, those
      aged 13-19 years were more exposed per viewing hour than adults aged >= 20 years
      (IRR = 1.29; 95% CI: 1.19, 1.39; P < 0.01). Conversely, in Germany, those aged 10
      15 years were less exposed to alcohol advertisements than adults aged >= 25 years
      (IRR = 0.79; 95% CI: 0.73, 0.85; P < 0.01). In each country, young children (aged
      4-9 years in the UK and Germany, 6-12 years in the Netherlands) were less exposed
      than adults. CONCLUSION: Adolescents in the UK and the Netherlands, but not
      Germany, had higher exposure to television alcohol advertising relative to adults
      than would be expected from their television viewing. Further work across a wider
      range of countries is needed to understand the relationship between national
      policies and youth exposure to alcohol advertising on television.

PMID- 24850784
TI  - Reliable protocols for whole-mount fluorescent in situ hybridization (FISH) in
      the pea aphid Acyrthosiphon pisum: a comprehensive survey and analysis.
AB  - RNA in situ hybridization (ISH), including chromogenic ISH (CISH) and fluorescent
      ISH (FISH), has become a powerful tool for revealing the spatial distribution of
      gene transcripts in model organisms. Previously, we developed a robust protocol
      for whole-mount RNA CISH in the pea aphid Acyrthosiphon pisum, an emerging insect
      genomic model. In order to improve the resolving capacity of gene detection, we
      comprehensively surveyed current protocols of whole-mount RNA-FISH and developed
      protocols that allow, using confocal microscopy, clearer visualization of target
      messenger RNAs (mRNAs) - including those subcellularly localized and those with
      spatially overlapping expression. We find that Fast dye-based substrate
      fluorescence (SF), tyramide signal amplification (TSA), and TSA Plus all enable
      identifying gene expression thanks to multiplex amplification of fluorescent
      signals. By contrast, methods of direct fluorescence (DF) do not allow
      visualizing signals. Detection of a single gene target was achieved with SF and
      TSA Plus for most mRNAs, whereas TSA only allowed visualization of abundant
      transcripts such as Apvas1 and Appiwi2 in the germ cells. For detection of
      multiple gene targets using double FISH, we recommend: (i) TSA/TSA, rather than
      TSA Plus/TSA Plus for colocalized mRNAs abundantly expressed in germ cells, as
      proteinase K treatment can be omitted; and (ii) SF/TSA Plus for other gene
      targets such as Apen1 and Apen2 as inactivation of enzyme conjugates is not
      required. SF/SF is not ideal for double FISH experiments due to signal blurring.
      Based on these new conditions for RNA-FISH, we have obtained a better
      understanding of germline specification and embryonic segmentation in the pea
      aphid. We anticipate that the RNA-FISH protocols for the pea aphid may also be
      used for other aphids and possibly other insect species, thus expanding the range
      of species from which useful insights into development and evolution may be
      obtained. 

PMID- 24850785
TI  - Demographics and survival trends of sinonasal adenocarcinoma from 1973 to 2009.
AB  - BACKGROUND: The purpose of this work was to study the demographics and survival
      of patients diagnosed with sinonasal adenocarcinoma (SNAC) within the time period
      of 1973 to 2009 using the Surveillance, Epidemiology, and End Result (SEER)
      database. METHODS: A retrospective cohort study using the U.S. National Cancer
      Institute's SEER registry was performed to study the demographics and survival
      for SNAC from 1973 to 2009. Analysis was conducted based on race, gender, and
      stage. RESULTS: In total, 1270 cases of SNAC were analyzed for demographics and
      survival. Males accounted for 51.6% of cases, while females accounted for 48.4%
      of cases, amounting to a male to female ratio of 1.06:1.00. Disease specific
      survival at 5, 10, 15, and 20 years was 65.2%, 50.9%, 40.9%, and 36.5%,
      respectively. When analyzed by gender, females had higher survival than males,
      although this difference was not statistically significant. When analyzed by
      race, the category of other, which encompasses American Indian, Asian, Hispanic,
      and unknown or unspecified race, was shown to have the best survival, followed by
      whites and blacks, respectively. CONCLUSION: SNAC is a rare tumor classically
      associated with occupational exposure and carries a variable prognosis. This is
      the first dedicated large-scale, retrospective analysis of a North American SNAC
      population. SNAC appears to affect both males and females equally and
      predominantly affects whites. Patients categorized as other had significantly
      better survival outcomes, while gender appeared to have no significant effect on
      survival.

PMID- 24850787
TI  - Design, synthesis, and biological evaluation of 1,3-diarylpropenones as dual
      inhibitors of HIV-1 reverse transcriptase.
AB  - A small library of 1,3-diarylpropenones was designed and synthesized as dual
      inhibitors of both HIV-1 reverse transcriptase (RT) DNA polymerase (DP) and
      ribonuclease H (RNase H) associated functions. Compounds were assayed on these
      enzyme activities, which highlighted dual inhibition properties in the low
      micromolar range. Interestingly, mutations in the non-nucleoside RT inhibitor
      binding pocket strongly affected RNase H inhibition by the propenone derivatives
      without decreasing their capacity to inhibit DP activity, which suggests long
      range RT structural effects. Biochemical and computational studies indicated that
      the propenone derivatives bind two different interdependent allosteric pockets. 

PMID- 24850789
TI  - Role of prostaglandin F2alpha production in lipid bodies from Leishmania infantum
      chagasi: insights on virulence.
AB  - Lipid bodies (LB; lipid droplets) are cytoplasmic organelles involved in lipid
      metabolism. Mammalian LBs display an important role in host-pathogen
      interactions, but the role of parasite LBs in biosynthesis of prostaglandin
      F2alpha (PGF2alpha) has not been investigated. We report herein that LBs
      increased in abundance during development of Leishmania infantum chagasi to a
      virulent metacyclic stage, as did the expression of PGF2alpha synthase (PGFS).
      The amount of parasite LBs and PGF2alpha were modulated by exogenous arachidonic
      acid. During macrophage infection, LBs were restricted to parasites inside the
      parasitophorous vacuoles (PV). We detected PGF2alpha receptor (FP) on the
      Leishmania PV surface. The blockage of FP with AL8810, a selective antagonist,
      hampered Leishmania infection, whereas the irreversible inhibition of
      cyclooxygenase with aspirin increased the parasite burden. These data demonstrate
      novel functions for parasite-derived LBs and PGF2alpha in the cellular metabolism
      of Leishmania and its evasion of the host immune response. 

PMID- 24850788
TI  - HIV type 1 (HIV-1) proviral reservoirs decay continuously under sustained
      virologic control in HIV-1-infected children who received early treatment.
AB  - BACKGROUND: Early initiation of combination antiretroviral therapy (cART) to
      human immunodeficiency virus type 1 (HIV-1)-infected infants controls HIV-1
      replication and reduces mortality. METHODS: Plasma viremia (lower limit of
      detection, <2 copies/mL), T-cell activation, HIV-1-specific immune responses, and
      the persistence of cells carrying replication-competent virus were quantified
      during long-term effective combination antiretroviral therapy (cART) in 4
      perinatally HIV-1-infected youth who received treatment early (the ET group) and
      4 who received treatment late (the LT group). Decay in peripheral blood
      mononuclear cell (PBMC) proviral DNA levels was also measured over time in the ET
      youth. RESULTS: Plasma viremia was not detected in any ET youth but was detected
      in all LT youth (median, 8 copies/mL; P = .03). PBMC proviral load was
      significantly lower in ET youth (median, 7 copies per million PBMCs) than in LT
      youth (median, 181 copies; P = .03). Replication-competent virus was recovered
      from all LT youth but only 1 ET youth. Decay in proviral DNA was noted in all 4
      ET youth in association with limited T-cell activation and with absent to minimal
      HIV-1-specific immune responses. CONCLUSIONS: Initiation of early effective cART
      during infancy significantly limits circulating levels of proviral and
      replication-competent HIV-1 and promotes continuous decay of viral reservoirs.
      Continued cART with reduction in HIV-1 reservoirs over time may facilitate HIV-1
      eradication strategies.

PMID- 24850790
TI  - Enhanced in vitro transcytosis of simian immunodeficiency virus mediated by
      vaccine-induced antibody predicts transmitted/founder strain number after rectal
      challenge.
AB  - BACKGROUND: The time to acquisition of simian immunodeficiency virus (SIV)
      infection following low-dose repeated rectal challenge correlated inversely with
      the number of transmitted/founder strains among macaques vaccinated with ALVAC
      SIV/gp120 or gp120 alone. We determined if the ability of postvaccination,
      prechallenge sera to enhance SIVmac251 transcytosis across epithelial cells was
      associated with transmitted/founder strain number. METHODS: Transcytosis was
      carried out by exposing sera and SIVmac251 to the apical surface of human
      endometrial carcinoma (HEC-1A) cells at pH 6.0 and 12 hours later quantifying
      virus in fluid bathing the basolateral cell surface (maintained at pH 7.4). These
      conditions allow Fc neonatal receptor (FcRn)-dependent shuttling of virus across
      cells. RESULTS: There was a strong correlation between the amount of virus
      transcytosed and number of transmitted variants (R = 0.86, P < .0001). We also
      found that 4 animals who remained uninfected after repeated rectal challenges had
      lower serum transcytosis activity than did 19 animals who subsequently became
      infected (P = .003). Using immunohistochemistry, we demonstrated FcRn on columnar
      epithelial cells facing the lumen of the macaque rectum. CONCLUSIONS: Vaccine
      induced antibody capable of enhancing transcytosis in vitro via FcRn may play a
      role in determining transmitted/founder strain number and infection outcomes
      following in vivo challenge.

PMID- 24850791
TI  - The sooner, the better: more evidence that early antiretroviral therapy lowers
      viral reservoirs in HIV-infected infants.

PMID- 24850792
TI  - Ergoline-derived inverse agonists of the human h3 receptor for the treatment of
      narcolepsy.
AB  - Ergoline derivative (6aR,9R)-4-(2-(dimethylamino)ethyl)-N-phenyl-9-(pyrrolidine-1
      carbonyl)-6,6a,8,9-tetrahydroindolo[4,3-fg]quinoline-7(4H)-carboxamide (1), a
      CXCR3 antagonist, also inhibits human histamine H3 receptors (H3R) and represents
      a structurally novel H3R inverse agonist chemotype. It displays favorable
      pharmacokinetic and in vitro safety profiles, and served as a lead compound in a
      program to explore ergoline derivatives as potential drug candidates for the
      treatment of narcolepsy. A key objective of this work was to enhance the safety
      and efficacy profiles of 1, while minimizing its duration of action to mitigate
      the episodes of insomnia documented with previously reported clinical candidates
      during the night following administration. Modifications to the ergoline core at
      positions 1, 6 and 8 were systematically investigated, and derivative 23 (1
      ((4aR,8R,9aR)-8-(hydroxymethyl)-1-(2-((R)-2-methylpyrrolidin-1-yl)ethyl)
      4,4a,7,8,9,9a-hexahydroindolo[1,14-fg]quinolin-6(1H)-yl)ethanone) was identified
      as a promising lead compound. Derivative 23 has a desirable pharmacokinetic
      profile and demonstrated efficacy by enhancing brain concentrations of tele
      methylhistamine, a major histamine metabolite. This validates the potential of
      the ergoline scaffold to serve as a template for the development of H3R inverse
      agonists. 

PMID- 24850793
TI  - Low-dose cisplatin administration to septic mice improves bacterial clearance and
      programs peritoneal macrophage polarization to M1 phenotype.
AB  - Sepsis is a systemic inflammatory response to infection, and early responses of
      macrophages are vital in controlling the infected microorganisms. We used a cecal
      ligation and puncture (CLP) model of sepsis to determine the role of cisplatin
      (0.1, 0.5 and 1 mg kg(-1)) with respect to peritoneal macrophages, controlling
      peritoneal/blood bacterial infection, and systemic inflammation. We found that
      mice which received low-dose (0.1 and 0.5 mg kg(-1)) i.p. cisplatin had lower
      mortality rate and improved clinical scores compared with mice in normal saline
      treated group, and the level of IL-6 and TNF-alpha was significantly reduced
      after cisplatin administration in peritoneal fluid of mice underwent CLP.
      Although cisplatin had no directly bactericidal ability, the numbers of bacteria
      in peritoneal and blood were significantly reduced at 24 and 72 h after the onset
      of CLP. Besides, in vivo phagocytosis and killing assay showed that the ability
      of macrophage derived from peritoneum was significantly increased with cisplatin
      treatment (5, 10, and 15 MUM) for both gram-positive (Enterococcus faecalis) and
      gram-negative (Escherichia coli) bacteria. This was associated with the
      macrophage phenotype polarization from CD11b(+) F4/80(high) CD206(-) to CD11b(+)
      F4/80(low) CD206(-) M1 group. These findings underscore the importance of low
      dose cisplatin in the treatment of sepsis.

PMID- 24850794
TI  - Refinement of indicators and criteria in a quality tool for assessing quality in
      primary care in Canada: a Delphi panel study.
AB  - PURPOSE: Primary care is the cornerstone of the health care system and
      increasingly countries are developing indicators for assessing quality in primary
      care practices. The 'Quality Tool', developed in Ontario, Canada, provides a
      framework for assessing practices and consists of indicators and criteria. The
      purpose of this study was to validate the indicators and simplify the Quality
      Tool. METHODS: This study involved a systematic comparison of indicators in the
      Quality Tool with those in other local and international tools to determine
      common indicators to include as valid in the Quality Tool. A Delphi process was
      used to help reach consensus for inclusion of any indicators that were not
      included in the comparison exercise. SETTING: Primary care in Ontario, Canada.
      SUBJECTS: Key informants were those with known expertise and experience in
      quality assessment in primary care. MAIN OUTCOME: Validated set of indicators for
      inclusion in an updated Quality Tool. RESULTS: Twenty-three stakeholders
      participated in the Delphi panel. Forty-four indicators were included as valid
      after the systematic comparison of similar indicators in other assessment tools.
      Of the 63 indicators brought to the Delphi panel, 37 were included as valid, 15
      were excluded and 11 became criteria for other included indicators. CONCLUSIONS:
      The study resulted in a set of 81 validated primary care indicators. The
      validation of the indicators provided a strong foundation for the next version of
      the Quality Tool and may be used for quality assessment in primary care.

PMID- 24850795
TI  - The monitoring of longer term prescriptions of antidepressants: observational
      study in a primary care setting.
AB  - BACKGROUND: There is little evidence to guide the frequency of review for
      patients taking antidepressants in the longer term. OBJECTIVES: To measure the
      frequency with which patients on longer term courses of antidepressants have
      their treatment monitored in primary care and to identify patient characteristics
      associated with the frequency of monitoring. METHODS: A cohort of patients who
      were receiving antidepressants continuously for at least two years was identified
      from four general practices. Data were collected from patients' general medical
      records. The dates of all GP consultations and whether they included a documented
      review of antidepressant therapy were recorded, along with patient
      characteristics hypothesized to influence the frequency of monitoring. RESULTS:
      The frequency of antidepressant review consultations and proportion of
      participants being reviewed during a specific year of antidepressant therapy
      decreased with increasing year of antidepressant therapy. Individuals who receive
      antidepressants for an overt mental health reason; undergo more dose and drug
      changes; and who are referred to the community mental health team have their
      antidepressant therapy reviewed more often during the first five years of
      antidepressant therapy. CONCLUSION: As many patients on longer term courses of
      antidepressants are not being appropriately reviewed, a 'chronic disease
      management approach' to depression in primary care is advocated.

PMID- 24850797
TI  - Endothelial transcriptome in response to pharmacological methyltransferase
      inhibition.
AB  - The enzymatic activities of protein methyltransferases serve to write covalent
      modifications on histone and non-histone proteins in the control of gene
      transcription. Here, we describe gene expression changes in human endothelial
      cells caused by treatment with methyltransferase inhibitors 7,7'-carbonylbis
      (azanediyl) bis(4-hydroxynaphthalene-2 -sulfonic acid (AMI-1) and disodium-2
      (2,4,5,7- tetrabromo-3-oxido-6-oxoxanthen-9-yl) benzoate trihydrate (AMI-5). Deep
      sequencing of mRNA indicated robust change on transcription following AMI-5
      treatment compared with AMI-1. Functional annotation analysis revealed that both
      compounds suppress the expression of genes associated with translational
      regulation, suggesting arginine methylation by protein arginine
      methyltransferases (PRMTs) could be associated with regulation of this pathway.
      Interestingly, AMI-5 but not AMI-1 was found to decrease methylation of H3
      histones at lysine 4 and down-regulate gene expression associated with
      interleukin-6 (IL-6) and activator protein-1 (AP-1) signaling pathways. These
      results imply that inhibition of protein methylation by AMI-1 and AMI-5 can
      differentially regulate specific pathways with potential to interrupt
      pathological signaling in the vascular endothelium. 

PMID- 24850796
TI  - Genomics of rapid adaptation to antibiotics: convergent evolution and scalable
      sequence amplification.
AB  - Evolutionary adaptation can be extremely fast, especially in response to high
      selection intensities. A prime example is the surge of antibiotic resistance in
      bacteria. The genomic underpinnings of such rapid changes may provide information
      on the genetic processes that enhance fast responses and the particular trait
      functions under selection. Here, we use experimentally evolved Escherichia coli
      for a detailed dissection of the genomics of rapid antibiotic resistance
      evolution. Our new analyses demonstrate that amplification of a sequence region
      containing several known antibiotic resistance genes represents a fast genomic
      response mechanism under high antibiotic stress, here exerted by drug
      combination. In particular, higher dosage of such antibiotic combinations
      coincided with higher copy number of the sequence region. The amplification
      appears to be evolutionarily costly, because amplification levels rapidly dropped
      after removal of the drugs. Our results suggest that amplification is a scalable
      process, as copy number rapidly changes in response to the selective pressure
      encountered. Moreover, repeated patterns of convergent evolution were found
      across the experimentally evolved bacterial populations, including those with
      lower antibiotic selection intensities. Intriguingly, convergent evolution was
      identified on different organizational levels, ranging from the above sequence
      amplification, high variant frequencies in specific genes, prevalence of
      individual nonsynonymous mutations to the unusual repeated occurrence of a
      particular synonymous mutation in Glycine codons. We conclude that constrained
      evolutionary trajectories underlie rapid adaptation to antibiotics. Of the
      identified genomic changes, sequence amplification seems to represent the most
      potent, albeit costly genomic response mechanism to high antibiotic stress. 

PMID- 24850798
TI  - Sonographic dynamic assessment of lung injury in a child with hypoplastic left
      heart syndrome undergoing extracorporeal membrane oxygenation.
AB  - INTRODUCTION: Performed for many years in clinical settings, pleural and lung
      ultrasound (PLUS) has emerged to be an invaluable tool to diagnose underlying
      conditions of respiratory failure, to monitor disease progression and to ensure
      appropriate therapeutic intervention. PLUS basically relies on the analysis of
      two prevalent ultrasound artefacts: A-lines and B-lines. A-lines are hyperechoic
      reverberation artefacts of the pleural line. A-lines combined with lung sliding
      show that lungs are well aerated. B-lines are vertical hyperechoic reverberation
      artefacts arising from pleural line extending to the bottom of the screen. The
      prevalence of B-lines indicates a pathologic parenchyma. Since PLUS is readily
      available, easily affordable, and biologically non-invasive, it is especially
      suitable for bedside clinical care in critically ill and unstable adult patients.
      Several authors have recently proposed PLUS for application in critically ill
      neonates and children. We report a case in which PLUS was used to clinically
      monitor a complex lung lesion during treatment of a child with congenital heart
      disease suffering from severe lung injury. CASE DESCRIPTION: A 1-year-old male
      with hypoplastic left heart syndrome underwent bidirectional Glenn procedure and
      systemic-to-left pulmonary artery shunt for heart palliation. After surgery, he
      developed a severe acute respiratory distress syndrome (ARDS) and extra-corporeal
      membrane oxygenation (ECMO) treatment was started. PLUS was performed daily to
      monitor the disease's progression and response to treatment during lung rest. As
      B-lines were decreasing and A-lines were becoming visible, we were able to
      monitor the improving aeration of the injured lung. The ultrasound showed high
      consistency with traditional imaging. DISCUSSION: Due to its non-ionizing nature,
      low cost, easy availability, easy repeatability and real-time results, PLUS is a
      feasible and beneficial bedside imaging technique for critically ill and unstable
      adult and pediatric patients. A reliable monitoring of ongoing treatments is
      certainly helpful to provide appropriate intervention, correctly schedule chest X
      ray and CT-scan, and optimize ECMO weaning. The present case suggests that PLUS
      may be a successful and useful tool for monitoring lung diseases in children with
      CHD with severe post-operative complex lung injury.

PMID- 24850799
TI  - Data on whole-genome sequencing are insufficient to rule out patient-to-patient
      transmission as a significant source of Staphylococcus aureus acquisition in an
      intensive care unit.

PMID- 24850800
TI  - Cutaneous leishmaniasis in North Dakota.
AB  - In the United States, autochthonous cutaneous leishmaniasis caused by infection
      with Leishmania mexicana has been reported from Texas and Oklahoma. Here, we
      describe a child with 2 new features: cutaneous infection acquired outside of the
      south-central United States (in North Dakota) and infection caused by Leishmania
      donovani species complex. 

PMID- 24850801
TI  - Donor cytomegalovirus status influences the outcome of allogeneic stem cell
      transplant: a study by the European group for blood and marrow transplantation.
AB  - BACKGROUND: The use of a cytomegalovirus (CMV)-seronegative donor for a CMV
      seronegative allogeneic hematopoietic stem cell transplant (HSCT) recipient is
      generally accepted. However, the importance of donor serostatus in CMV
      seropositive patients is controversial. METHODS: A total of 49 542 HSCT patients,
      29 349 seropositive and 20 193 seronegative, were identified from the European
      Group for Blood and Marrow Transplantation database. Cox multivariate models were
      fitted to estimate the effect of donor CMV serological status on outcome.
      RESULTS: Seronegative patients receiving seropositive unrelated-donor grafts had
      decreased overall survival (hazard ratio [HR], 1.13; 95% confidence interval
      [CI], 1.06-1.21; P < .0001) compared with seronegative donors, whereas no
      difference was seen in patients receiving HLA-matched sibling grafts.
      Seropositive patients receiving grafts from seropositive unrelated donors had
      improved overall survival (HR, 0.92; 95% CI, .86-.98; P < .01) compared with
      seronegative donors, if they had received myeloablative conditioning. This effect
      was absent when they received reduced-intensity conditioning. No effect was seen
      in patients grafted from HLA-identical sibling donors. The same association was
      found if the study was limited to patients receiving transplants from the year
      2000 onward. CONCLUSIONS: We confirm the negative impact on overall survival if a
      CMV-seropositive unrelated donor is selected for a CMV-seronegative patient. For
      a CMV-seropositive patient, our data support selecting a CMV-seropositive donor
      if the patient receives a myeloablative conditioning regimen.

PMID- 24850802
TI  - Reply to Mills and Linkin.

PMID- 24850803
TI  - Editorial commentary: the complexity of latent cytomegalovirus infection in stem
      cell donors.

PMID- 24850804
TI  - Enhancement of lithium storage performance of carbon microflowers by achieving a
      high surface area.
AB  - High-surface-area, nitrogen-doped carbon microflowers (A-NCFs-4) assembled from
      porous nanosheets are prepared in a three-step process: soft-templating self
      assembly, thermal decomposition, and KOH activation. The hydrazine hydrate used
      in our experiment serves not only as a structure-directing agent, but also as a
      nitrogen source. The resultant A-NCFs-4 has a hierarchical porous structure and
      its specific surface area is as high as 2309 m(2)  g(-1). When used as anode, it
      exhibits a reversible capacity as high as 807 mAh g(-1) at 300 mA g(-1) after 100
      cycles, and an excellent rate capability of 200 mAh g(-1) at a high current
      density of 8 A g(-1). Compared with unactivated counterpart, A-NCFs-4 exhibits a
      significantly improved lithium storage capacity and rate capability; this can be
      attributed to its unique structural characteristics and high surface area. The
      hierarchical micro-/mesopore structure, high surface area, and nitrogen doping of
      A-NCFs-4 could guarantee fast mass transport for lithium species, enhance the A
      NCFs-4/electrolyte contact area, shorten the lithium-ion diffusion length, and
      accommodate strain induced by volume changes during the electrochemical reaction.
      The results indicate that the as-prepared A-NCFs-4 could be a promising candidate
      as a high-performance anode for lithium-ion batteries.

PMID- 24850805
TI  - Cumulative neonatal oxygen exposure predicts response of adult mice infected with
      influenza A virus.
AB  - An acceptable level of oxygen exposure in preterm infants that maximizes efficacy
      and minimizes harm has yet to be determined. Quantifying oxygen exposure as an
      area-under-the curve (OAUC ) has been predictive of later respiratory symptoms
      among former low birth weight infants. Here, we test the hypothesis that
      quantifying OAUC in newborn mice can predict their risk for altered lung
      development and respiratory viral infections as adults. Newborn mice were exposed
      to room air or a FiO2 of 100% oxygen for 4 days, 60% oxygen for 8 days, or 40%
      oxygen for 16 days (same cumulative dose of excess oxygen). At 8 weeks of age,
      mice were infected intranasally with a non-lethal dose of influenza A virus.
      Adult mice exposed to 100% oxygen for 4 days or 60% oxygen for 8 days exhibited
      alveolar simplification and altered elastin deposition compared to siblings
      birthed into room air, as well as increased inflammation and fibrotic lung
      disease following viral infection. These changes were not observed in mice
      exposed to 40% oxygen for 16 days. Our findings in mice support the concept that
      quantifying OAUC over a currently unspecified threshold can predict human risk
      for respiratory morbidity later in life. Pediatr Pulmonol. 2015; 50:222-230. (c)
      2014 Wiley Periodicals, Inc.

PMID- 24850806
TI  - Kinetic assay of the Michael addition-like thiol-ene reaction and insight into
      protein bioconjugation.
AB  - The chemical modification of proteins is a valuable technique in understanding
      the functions, interactions, and dynamics of proteins. Reactivity and selectivity
      are key issues in current chemical modification of proteins. The Michael addition
      like thiol-ene reaction is a useful tool that can be used to tag proteins with
      high selectivity for the solvent-exposed thiol groups of proteins. To obtain
      insight into the bioconjugation of proteins with this method, a kinetic analysis
      was performed. New vinyl-substituted pyridine derivatives were designed and
      synthesized. The reactivity of these vinyl tags with L-cysteine was evaluated by
      UV absorption and high-resolution NMR spectroscopy. The results show that
      protonation of pyridine plays a key role in the overall reaction rates. The
      kinetic parameters were assessed in protein modification. The different
      reactivities of these vinyl tags with solvent-exposed cysteine is valuable
      information in the selective labeling of proteins with multiple functional
      groups. 

PMID- 24850807
TI  - Selective inhibitors of a PAF biosynthetic enzyme lysophosphatidylcholine
      acyltransferase 2.
AB  - Platelet-activating factor (PAF) is a potent pro-inflammatory phospholipid
      mediator. In response to extracellular stimuli, PAF is rapidly biosynthesized by
      lyso-PAF acetyltransferase (lyso-PAFAT). Previously, we identified two types of
      lyso-PAFATs: lysophosphatidylcholine acyltransferase (LPCAT)1, mostly expressed
      in the lungs where it produces PAF and dipalmitoyl-phosphatidylcholine essential
      for respiration, and LPCAT2, which biosynthesizes PAF and phosphatidylcholine
      (PC) in the inflammatory cells. Under inflammatory conditions, LPCAT2, but not
      LPCAT1, is activated and upregulated to produce PAF. Thus, it is important to
      develop inhibitors specific for LPCAT2 in order to ameliorate PAF-related
      inflammatory diseases. Here, we report the first identification of LPCAT2
      specific inhibitors, N-phenylmaleimide derivatives, selected from a 174,000
      compound library using fluorescence-based high-throughput screening followed by
      the evaluation of the effects on LPCAT1 and LPCAT2 activities, cell viability,
      and cellular PAF production. Selected compounds competed with acetyl-CoA for the
      inhibition of LPCAT2 lyso-PAFAT activity and suppressed PAF biosynthesis in mouse
      peritoneal macrophages stimulated with a calcium ionophore. These compounds had
      low inhibitory effects on LPCAT1 activity, indicating that adverse effects on
      respiratory functions may be avoided. The identified compounds and their
      derivatives will contribute to the development of novel drugs for PAF-related
      diseases and facilitate the analysis of LPCAT2 functions in phospholipid
      metabolism in vivo.

PMID- 24850808
TI  - Robust validation of methylation levels association at CPT1A locus with lipid
      plasma levels.

PMID- 24850809
TI  - Genetic determinants of P wave duration and PR segment.
AB  - BACKGROUND: The PR interval on the ECG reflects atrial depolarization and
      atrioventricular nodal delay which can be partially differentiated by P wave
      duration and PR segment, respectively. Genome-wide association studies have
      identified several genetic loci for PR interval, but it remains to be determined
      whether this is driven by P wave duration, PR segment, or both. METHODS AND
      RESULTS: We replicated 7 of the 9 known PR interval loci in 16 468 individuals of
      European ancestry. Four loci were unambiguously associated with PR segment, while
      the others were shared for P wave duration and PR segment. Next, we performed a
      genome-wide analysis on P wave duration and PR segment separately and identified
      5 novel loci. Single-nucleotide polymorphisms in KCND3 (P=8.3*10(-11)) and FADS2
      (P=2.7*10(-8)) were associated with P wave duration, whereas single-nucleotide
      polymorphisms near IL17D (P=2.3*10(-8)), in EFHA1 (P=3.3*10(-10)), and in LRCH1
      (P=2.1*10(-8)) were associated with PR segment. Analysis on DNA elements
      indicated that genome-wide significant single-nucleotide polymorphisms were
      enriched at genomic regions suggesting active gene transcription in the human
      right atrium. Quantitative polymerase chain reaction showed that genes were
      significantly higher expressed in the right atrium and atrioventricular node
      compared with left ventricle (P=5.6*10(-6)). CONCLUSIONS: Genetic associations of
      PR interval seem to be mainly driven by genetic determinants of the PR segment.
      Some of the PR interval associations are strengthened by a directional consistent
      effect of genetic determinants of P wave duration. Through genome-wide
      association we also identified genetic variants specifically associated with P
      wave duration which might be relevant for cardiac biology.

PMID- 24850811
TI  - In this issue of Occupational Medicine.

PMID- 24850810
TI  - Soluble vascular adhesion protein-1 predicts incident major adverse
      cardiovascular events and improves reclassification in a finnish prospective
      cohort study.
AB  - BACKGROUND: Vascular adhesion protein-1 (VAP-1) associates to subclinical
      atherosclerotic manifestations in young people, but its association to incident
      major adverse cardiovascular events (MACEs) and cardiovascular mortality in a
      general population is not known. METHODS AND RESULTS: We used a newly developed
      ELISA to measure soluble VAP-1 (sVAP-1) levels in 2775 participants (mean age, 60
      years) from a prospective cohort study (the FINRISK 2002). During a mean follow
      up of 9 years, 265 participants underwent a MACE, and these participants had
      higher levels of sVAP-1 than those without MACE (868 ng/mL and 824 ng/mL,
      respectively, P<0.001). In multivariate-adjusted Cox proportional hazard model
      including traditional Framingham risk factors (age, sex, systolic blood pressure,
      cholesterol, high-density lipoprotein cholesterol, smoking, prevalent diabetes
      mellitus, and antihypertensive treatment), sVAP-1 independently predicted
      incident MACE (P=0.0046) and MACE mortality (P=0.026). The impact of sVAP-1 in
      predicting the 9-year absolute risk of MACE was analyzed using integrated
      discrimination improvement and net reclassification improvement with 10-fold
      cross-validation. Inclusion of sVAP-1 in the Framingham model improved integrated
      discrimination improvement (P=0.042), and the clinical net reclassification
      improvement by correctly reclassifying 9% (P=0.0019) of people in the
      intermediate risk (5%-20%) group. CONCLUSIONS: sVAP-1 associated with increased
      risk of MACE and MACE mortality in people aged >50 years without prior MACE, and
      inclusion of sVAP-1 in the risk prediction model improved the clinical net
      reclassification improvement of incident MACE. Thus, sVAP-1 may be a potential
      new biomarker for cardiovascular diseases.

PMID- 24850812
TI  - Sudden cardiac death in the fire service.

PMID- 24850813
TI  - Fire service pensions review.

PMID- 24850814
TI  - Dr Lachlan Grant (1871-1945).

PMID- 24850815
TI  - Do workplace physical activity interventions improve mental health outcomes?
AB  - BACKGROUND: Mental health is an important issue in the working population.
      Interventions to improve mental health have included physical activity. AIMS: To
      review evidence for the effectiveness of workplace physical activity
      interventions on mental health outcomes. METHODS: A literature search was
      conducted for studies published between 1990 and August 2013. Inclusion criteria
      were physical activity trials, working populations and mental health outcomes.
      Study quality was assessed using the Jadad scale. RESULTS: Of 3684 unique
      articles identified, 17 met all selection criteria, including 13 randomized
      controlled trials, 2 comparison trials and 2 controlled trials. Studies were
      grouped into two key intervention areas: physical activity and yoga exercise. Of
      eight high-quality trials, two provided strong evidence for a reduction in
      anxiety, one reported moderate evidence for an improvement in depression symptoms
      and one provided limited evidence on relieving stress. The remaining trials did
      not provide evidence on improved mental well-being. CONCLUSIONS: Workplace
      physical activity and yoga programmes are associated with a significant reduction
      in depressive symptoms and anxiety, respectively. Their impact on stress relief
      is less conclusive.

PMID- 24850817
TI  - Fifty years ago: 'The first group occupational health service in Scotland'. 1964.

PMID- 24850818
TI  - Factors influencing early retirement intentions in Australian rural general
      practitioners.
AB  - BACKGROUND: The Australian general practice workforce is ageing. This and a trend
      towards higher exit intentions and earlier retirement make it increasingly
      important to identify those work and personal factors affecting intention to
      leave, which are amenable to change. AIMS: To assess the various work,
      occupational and individual health factors associated with early retirement
      intentions among Australian rural general practitioners (GPs) that may be
      amenable to intervention. METHODS: A cross-sectional study of GPs practising in
      rural Australia. Odds ratios of early retirement intentions across work,
      occupational and individual health factors were calculated. RESULTS: There were
      92 participants (response rate 56%), and 47% of responders intended to retire
      before 65. GPs with medium to high burnout levels had higher odds of intending to
      retire. Increased job satisfaction and work ability scores were associated with
      decreased retirement intentions, whereas increased physical and mental work
      ability demands were associated with an increase in retirement intentions.
      Absenteeism was not related to retirement intentions but presenteeism was. GPs
      reporting any work-related sleep problems were found to have a 3-fold increase in
      the odds of early retirement intentions. The odds of early retirement intentions
      also increased with higher psychological distress, worsening general health and
      longer working hours. CONCLUSIONS: From a health policy reform perspective, the
      greatest impact on reducing early retirement intentions among ageing GPs could
      potentially be made by intervening in areas of working hours, burnout and work
      related sleep issues, followed by job satisfaction, psychological distress,
      health, general workability and mental and physical work ability.

PMID- 24850819
TI  - The AUDIT questionnaire.

PMID- 24850820
TI  - Genome properties and prospects of genomic prediction of hybrid performance in a
      breeding program of maize.
AB  - Maize (Zea mays L.) serves as model plant for heterosis research and is the crop
      where hybrid breeding was pioneered. We analyzed genomic and phenotypic data of
      1254 hybrids of a typical maize hybrid breeding program based on the important
      Dent * Flint heterotic pattern. Our main objectives were to investigate genome
      properties of the parental lines (e.g., allele frequencies, linkage
      disequilibrium, and phases) and examine the prospects of genomic prediction of
      hybrid performance. We found high consistency of linkage phases and large
      differences in allele frequencies between the Dent and Flint heterotic groups in
      pericentromeric regions. These results can be explained by the Hill-Robertson
      effect and support the hypothesis of differential fixation of alleles due to
      pseudo-overdominance in these regions. In pericentromeric regions we also found
      indications for consistent marker-QTL linkage between heterotic groups. With
      prediction methods GBLUP and BayesB, the cross-validation prediction accuracy
      ranged from 0.75 to 0.92 for grain yield and from 0.59 to 0.95 for grain
      moisture. The prediction accuracy of untested hybrids was highest, if both
      parents were parents of other hybrids in the training set, and lowest, if none of
      them were involved in any training set hybrid. Optimizing the composition of the
      training set in terms of number of lines and hybrids per line could further
      increase prediction accuracy. We conclude that genomic prediction facilitates a
      paradigm shift in hybrid breeding by focusing on the performance of experimental
      hybrids rather than the performance of parental lines in test crosses.

PMID- 24850822
TI  - Theresa Marteau: Tackling behaviour change.

PMID- 24850823
TI  - Cannabis regulation: high time for change?

PMID- 24850824
TI  - Deprivation of liberty in healthcare.

PMID- 24850821
TI  - Use of placebo controls in the evaluation of surgery: systematic review.
AB  - OBJECTIVE: To investigate whether placebo controls should be used in the
      evaluation of surgical interventions. DESIGN: Systematic review. DATA SOURCES: We
      searched Medline, Embase, and the Cochrane Controlled Trials Register from their
      inception to November 2013. STUDY SELECTION: Randomised clinical trials comparing
      any surgical intervention with placebo. Surgery was defined as any procedure that
      both changes the anatomy and requires a skin incision or use of endoscopic
      techniques. DATA EXTRACTION: Three reviewers (KW, BJFD, IR) independently
      identified the relevant trials and extracted data on study details, outcomes, and
      harms from included studies. RESULTS: In 39 out of 53 (74%) trials there was
      improvement in the placebo arm and in 27 (51%) trials the effect of placebo did
      not differ from that of surgery. In 26 (49%) trials, surgery was superior to
      placebo but the magnitude of the effect of the surgical intervention over that of
      the placebo was generally small. Serious adverse events were reported in the
      placebo arm in 18 trials (34%) and in the surgical arm in 22 trials (41.5%); in
      four trials authors did not specify in which arm the events occurred. However, in
      many studies adverse events were unrelated to the intervention or associated with
      the severity of the condition. The existing placebo controlled trials
      investigated only less invasive procedures that did not involve laparotomy,
      thoracotomy, craniotomy, or extensive tissue dissection. CONCLUSIONS: Placebo
      controlled trial is a powerful, feasible way of showing the efficacy of surgical
      procedures. The risks of adverse effects associated with the placebo are small.
      In half of the studies, the results provide evidence against continued use of the
      investigated surgical procedures. Without well designed placebo controlled trials
      of surgery, ineffective treatment may continue unchallenged.

PMID- 24850825
TI  - Four in 10 NHS staff believe it responds inadequately to poor performance, survey
      finds.

PMID- 24850826
TI  - Judge condemns GMC for "unacceptable delays" and inactivity.

PMID- 24850827
TI  - Number of people with health insurance has risen by 9.3 million since Affordable
      Care Act, US study finds.

PMID- 24850828
TI  - Taking a longer term view of cardiovascular risk: the causal exposure paradigm.

PMID- 24850829
TI  - Influence of cytokines on Dmt1 iron transporter and ferritin expression in
      insulin-secreting cells.
AB  - Free intracellular ferrous iron (Fe(2+)) is essential for the generation of the
      extremely toxic hydroxyl radicals, which contribute to beta-cell destruction by
      cytokines. Therefore the expression of the different divalent metal transporter 1
      (Dmt1) isoforms and ferritin (Ft) subunits, responsible for iron import and
      chelation, was analyzed under pro-inflammatory conditions (IL1beta alone or
      together with TNFalpha+IFNgamma). The Dmt1 isoforms (1A/1B and +IRE/-IRE) and the
      total Dmt1 expression in insulin-producing cells (RINm5F and INS-1E), in primary
      rat islets and, for comparison, in the neuroendocrine PC12 cell line were
      quantified by qRT-PCR. In addition, the expression of the light (L-Ft) and heavy
      Ft (H-Ft) subunits and the mitochondrial Ft isoform (Mtft) in insulin-producing
      cells under control conditions and after cytokine treatment was estimated. The 1B
      isoform was the predominant Dmt1 mRNA in all insulin-producing cells, accounting
      for almost 100% of the 1A/1B isoform expression. For the IRE variants, +IRE
      expression was higher than -IRE expression. Pro-inflammatory cytokines
      accelerated the expression of Dmt1 isoforms significantly with an overall 2.5- to
      3-fold increase in the total Dmt1 expression. In contrast, the expression of the
      iron-buffering ferritin subunits L- and H-Ft was unaffected by IL1beta and only
      slightly induced by the cytokine mixture. Mtft expression was also not increased.
      Dmt1 expression was significantly elevated through pro-inflammatory cytokines,
      whereas Ft expression was marginally increased. This imbalance between the
      increased iron transport capacity and the almost unaffected iron storage capacity
      can foster cytokine-mediated formation of hydroxyl radicals and thus pro
      inflammatory cytokine toxicity through elevated free iron concentrations.

PMID- 24850830
TI  - miR-135a-5p inhibits 3T3-L1 adipogenesis through activation of canonical Wnt/beta
      catenin signaling.
AB  - MicroRNAs are endogenous, conserved, and non-coding small RNAs that function as
      post-transcriptional regulators of fat development and adipogenesis. Adipogenic
      marker genes, such as CCAAT/enhancer binding protein alpha (Cebpa), peroxisome
      proliferator-activated receptor gamma (Pparg), adipocyte fatty acid binding
      protein (Ap2), and fatty acid synthase (Fas), are regarded as the essential
      transcriptional regulators of preadipocyte differentiation and lipid storage in
      mature adipocytes. Canonical Wnt/beta-catenin signaling is recognized as a
      negative molecular switch during adipogenesis. In the present work we found that
      miR-135a-5p is markedly downregulated during the process of 3T3-L1 preadipocyte
      differentiation. Overexpression of miR-135a-5p impairs the expressions of
      adipogenic marker genes as well as lipid droplet accumulation and triglyceride
      content, indicating the importance of miR-135a-5p for adipogenic differentiation
      and adipogenesis. Further studies show that miR-135a-5p directly targets
      adenomatous polyposis coli (Apc), contributes to the translocation of beta
      catenin from cytoplasm to nucleus, and then activates the expressions of cyclin
      D1 (Ccnd1) and Cmyc, indicating the induction of canonical Wnt/beta-catenin
      signaling. In addition, inhibition of APC with siRNA exhibits the same effects as
      overexpression of miR-135a-5p. Our findings demonstrate that miR-135a-5p
      suppresses 3T3-L1 preadipocyte differentiation and adipogenesis through the
      activation of canonical Wnt/beta-catenin signaling by directly targeting Apc.
      Taken together, these results offer profound insights into the adipogenesis
      mechanism and the development of adipose tissue. 

PMID- 24850831
TI  - Three intragenic suppressors of a GTPase-deficient allele of GNAS associated with
      McCune-Albright syndrome.
AB  - Gain-of-function mutations in heterotrimeric G-protein alpha subunits are
      associated with a variety of human diseases. McCune-Albright syndrome (MAS) is
      caused by mutations in GNAS, the gene encoding Gs. Alterations at Arg201
      significantly reduce the GTPase activity of the protein, rendering it
      constitutively active. In this study, we have constructed a library of random
      mutations in a constitutively active yeast GPA1 gene carrying a mutation
      homologous to the McCune-Albright allele (Arg297His). Intragenic suppressors
      found at sites with homology to the human Gs protein were tested for their
      ability to suppress the constitutive activity of an Arg201His mutation in Gs.
      Three intragenic suppressors, at Phe142, Arg231, and Leu266, were able to
      suppress elevated basal cAMP responses caused by Arg201His when expressed in
      HEK293 cells. A range of amino acid substitutions was introduced at each of these
      sites to investigate the chemical requirements for intragenic suppression. The
      ability of Gs proteins carrying the suppressor mutations alone to mediate
      receptor-induced cAMP production was measured. These results offer potential
      sites on Gs that could serve as drug targets for MAS therapies. 

PMID- 24850833
TI  - Identification of oxidatively modified proteins in salt-stressed Arabidopsis: a
      carbonyl-targeted proteomics approach.
AB  - In plants, environmental stresses cause an increase in the intracellular level of
      reactive oxygen species (ROS), leading to tissue injury. To obtain biochemical
      insights into this damage process, we investigated the protein carbonyls formed
      by ROS or by the lipid peroxide-derived alpha,beta-unsaturated aldehydes and
      ketones (i.e. reactive carbonyl species, or RCS) in the leaves of Arabidopsis
      thaliana under salt stress. A. thaliana Col-0 plants that we treated with 300 mM
      NaCl for 72 h under continuous illumination suffered irreversible leaf damage.
      Several RCS such as 4-hydroxy-(E)-2-nonenal (HNE) were increased within 12 h of
      this salt treatment. Immunoblotting using distinct antibodies against five
      different RCS, i.e. HNE, 4-hydroxy-(E)-2-hexenal, acrolein, crotonaldehyde and
      malondialdehyde, revealed that RCS-modified proteins accumulated in leaves with
      the progress of the salt stress treatment. The band pattern of Western blotting
      suggested that these different RCS targeted a common set of proteins. To identify
      the RCS targets, we collected HNE-modified proteins via an anti-HNE antiserum
      affinity trap and performed an isobaric tag for relative and absolute
      quantitation, as a quantitative proteomics approach. Seventeen types of protein,
      modified by 2-fold more in the stressed plants than in the non-stressed plants,
      were identified as sensitive RCS targets. With aldehyde-reactive probe-based
      affinity trapping, we collected the oxidized proteins and identified 22
      additional types of protein as sensitive ROS targets. These RCS and ROS target
      proteins were distributed in the cytosol and apoplast, as well as in the ROS
      generating organelles the peroxisome, chloroplast and mitochondrion, suggesting
      the participation of plasma membrane oxidation in the cellular injury. Possible
      mechanisms by which these modified targets cause cell death are discussed. 

PMID- 24850834
TI  - Tandem CCCH zinc finger proteins in plant growth, development and stress
      response.
AB  - Cysteine3Histidine (CCCH)-type zinc finger proteins comprise a large family that
      is well conserved across eukaryotes. Among them, tandem CCCH zinc finger proteins
      (TZFs) play critical roles in mRNA metabolism in animals and yeast. While there
      are only three TZF members in humans, a much higher number of TZFs has been found
      in many plant species. Notably, plant TZFs are over-represented by a class of
      proteins containing a unique TZF domain preceded by an arginine (R)-rich (RR)
      motif, hereafter called RR-TZF. Recently, there have been a large number of
      reports indicating that RR-TZF proteins can localize to processing bodies (P
      bodies) and stress granules (SG), two novel cytoplasmic aggregations of messenger
      ribonucleoprotein complexes (mRNPs), and play critical roles in plant growth,
      development and stress response, probably via RNA regulation. This review focuses
      on the classification and most recent development of molecular, cellular and
      genetic analyses of plant RR-TZF proteins. 

PMID- 24850832
TI  - Transcriptional analysis of endocrine disruption using zebrafish and massively
      parallel sequencing.
AB  - Endocrine-disrupting chemicals (EDCs), including plasticizers, pesticides,
      detergents, and pharmaceuticals, affect a variety of hormone-regulated
      physiological pathways in humans and wildlife. Many EDCs are lipophilic molecules
      and bind to hydrophobic pockets in steroid receptors, such as the estrogen
      receptor and androgen receptor, which are important in vertebrate reproduction
      and development. Indeed, health effects attributed to EDCs include reproductive
      dysfunction (e.g. reduced fertility, reproductive tract abnormalities, and skewed
      male:female sex ratios in fish), early puberty, various cancers, and obesity. A
      major concern is the effects of exposure to low concentrations of endocrine
      disruptors in utero and post partum, which may increase the incidence of cancer
      and diabetes in adults. EDCs affect transcription of hundreds and even thousands
      of genes, which has created the need for new tools to monitor the global effects
      of EDCs. The emergence of massive parallel sequencing for investigating gene
      transcription provides a sensitive tool for monitoring the effects of EDCs on
      humans and other vertebrates, as well as elucidating the mechanism of action of
      EDCs. Zebrafish conserve many developmental pathways found in humans, which makes
      zebrafish a valuable model system for studying EDCs, especially on early organ
      development because their embryos are translucent. In this article, we review
      recent advances in massive parallel sequencing approaches with a focus on
      zebrafish. We make the case that zebrafish exposed to EDCs at different stages of
      development can provide important insights on EDC effects on human health. 

PMID- 24850835
TI  - Physiological functions of PsbS-dependent and PsbS-independent NPQ under
      naturally fluctuating light conditions.
AB  - The PsbS protein plays an important role in dissipating excess light energy as
      heat in photosystem II (PSII). However, the physiological importance of PsbS
      under naturally fluctuating light has not been quantitatively estimated. Here we
      investigated energy allocation in PSII in PsbS-suppressed rice transformants
      (DeltapsbS) under both naturally fluctuating and constant light conditions. Under
      constant light, PsbS was essential for inducing the rapid formation of light
      inducible thermal dissipation (Phi(NPQ)), which consequently suppressed the rapid
      formation of basal intrinsic decay (Phi(f,D)), while the quantum yield of
      electron transport (Phi(II)) did not change. In the steady state phase, the
      difference between the wild type (WT) and DeltapsbS was minimized. Under
      regularly fluctuating light, the reduced PsbS resulted in higher Phi(II) upon the
      transition from high light to low light and in lower Phi(II) upon the transition
      from low light to high light, indicating that Phi(II) was, to some extent,
      controlled by PsbS. Under naturally fluctuating light in a greenhouse, rapid
      changes in Phi(II) were compensated by Phi(NPQ) in the WT, but by Phi(f,D) in
      DeltapsbS. As a consequence, a significantly lower SigmaNPQ integrated Phi(NPQ)
      over a whole day) and higher Sigmaf,D were found in DeltapsbS. Furthermore,
      thermal dissipation associated with photoinhibtion was enhanced in DeltapsbS.
      These results suggest that PsbS plays an important role in photoprotective
      process at the induction phase of photosynthesis as well as under field
      conditions. The physiological relevance of PsbS as a photoprotection mechanism
      and the identities of Phi(NPQ) and Phi(f,D) are discussed.

PMID- 24850836
TI  - Brassica oleracea MATE encodes a citrate transporter and enhances aluminum
      tolerance in Arabidopsis thaliana.
AB  - The secretion of organic acid anions from roots is an important mechanism for
      plant aluminum (Al) tolerance. Here we report cloning and characterizing BoMATE
      (KF031944), a multidrug and toxic compound extrusion (MATE) family gene from
      cabbage (Brassica oleracea). The expression of BoMATE was more abundant in roots
      than in shoots, and it was highly induced by Al treatment. The (14)C-citrate
      efflux experiments in oocytes demonstrated that BoMATE is a citrate transporter.
      Electrophysiological analysis and SIET analysis of Xenopus oocytes expressing
      BoMATE indicated BoMATE is activated by Al. Transient expression of BoMATE in
      onion epidermal cells demonstrated that it localized to the plasma membrane.
      Compared with the wild-type Arabidopsis, the transgenic lines constitutively
      overexpressing BoMATE enhanced Al tolerance and increased citrate secretion. In
      addition, Arabidopsis transgenic lines had a lower K(+) efflux and higher H(+)
      efflux, in the presence of Al, than control wild type in the distal elongation
      zone (DEZ). This is the first direct evidence that MATE protein is involved in
      the K(+) and H(+) flux in response to Al treatment. Taken together, our results
      show that BoMATE is an Al-induced citrate transporter and enhances aluminum
      tolerance in Arabidopsis thaliana. 

PMID- 24850837
TI  - Distinct redox behaviors of chloroplast thiol enzymes and their relationships
      with photosynthetic electron transport in Arabidopsis thaliana.
AB  - The thiol/disulfide redox network mediated by the thioredoxin (Trx) system in
      chloroplasts ensures light-responsive control of diverse crucial functions.
      Despite the suggested importance of this system, the working dynamics against
      changing light environments remains largely unknown. Thus, we directly assessed
      the in vivo redox behavior of chloroplast Trx-targeted thiol enzymes in
      Arabidopsis thaliana. In a time-course analysis throughout a day period that was
      artificially mimicked to natural light conditions, thiol enzymes showed a light
      dependent shift in redox state, but the patterns were distinct among thiol
      enzymes. Notably, the ATP synthase CF(1-gamma) subunit was rapidly reduced even
      under low-light conditions, whereas the stromal thiol enzymes fructose 1,6
      bisphosphatase, sedoheptulose 1,7-bisphosphatase, and NADP-malate dehydrogenase
      were gradually reduced/re-oxidized along with the increase/decrease in light
      intensity. Photo-reduction of thiol enzymes was suppressed by the impairment of
      photosynthetic linear electron transport using DCMU and 2,5-dibromo-3-methyl-6
      isopropyl-p-benzoquinone, but sensitivity to the impairment was uneven between
      CF(1-gamma) and other stromal thiol enzymes. These different dependencies of
      photo-reduction on electron transport, rather than the redox state of Trx and the
      circadian clock, could readily explain the distinct diurnal redox behaviors of
      thiol enzymes. In addition, our results indicate that the cyclic electron
      transport around PSI is also involved in redox regulation of some thiol enzymes.
      Based on these findings, we propose an in vivo working model of the redox
      regulation system in chloroplasts.

PMID- 24850838
TI  - Transcriptional regulation of the stress-responsive light harvesting complex
      genes in Chlamydomonas reinhardtii.
AB  - Dissipating excess energy of light is critical for photosynthetic organisms to
      keep the photosynthetic apparatus functional and less harmful under stressful
      environmental conditions. In the green alga Chlamydomonas reinhardtii, efficient
      energy dissipation is achieved by a process called non-photochemical quenching
      (NPQ), in which a distinct member of light harvesting complex, LHCSR, is known to
      play a key role. Although it has been known that two very closely related genes
      (LHCSR3.1 and LHCSR3.2) encoding LHCSR3 protein and another paralogous gene
      LHCSR1 are present in the C. reinhardtii genome, it is unclear how these isoforms
      are differentiated in terms of transcriptional regulation and functionalization.
      Here, we show that transcripts of both of the isoforms, LHCSR3.1 and LHCSR3.2,
      are accumulated under high light stress. Reexamination of the genomic sequence
      and gene models along with survey of sequence motifs suggested that these two
      isoforms shared an almost identical but still distinct promoter sequence and a
      completely identical polypeptide sequence, with more divergent 3'-untranscribed
      regions. Transcriptional induction under high light condition of both isoforms
      was suppressed by treatment with a photosystem II inhibitor, 3-(3,4
      dichlorophenyl)-1,1-dimethylurea (DCMU), and a calmodulin inhibitor W7. Despite a
      similar response to high light, the inhibitory effects of DCMU and W7 to the
      LHCSR1 transcript accumulation were limited compared to LHCSR3 genes. These
      results suggest that the transcription of LHCSR paralogs in C. reinhardtii are
      regulated by light signal and differentially modulated via photosynthetic
      electron transfer and calmodulin-mediated calcium signaling pathway(s). 

PMID- 24850839
TI  - Investigating the photoprotective role of cytochrome b-559 in photosystem II in a
      mutant with altered ligation of the haem.
AB  - Despite many years of study, the physiological role of cytochrome b-559 (Cyt b
      559) within the photosystem II (PSII) complex still remains unclear. Here we
      describe the analysis of a mutant of the green alga Chlamydomonas reinhardtii in
      which the His ligand to the haem, provided by the alpha subunit, has been
      replaced by a Cys residue. The mutant is unable to grow photoautotrophically but
      can assemble oxygen-evolving PSII supercomplexes to 15-20% of the levels found in
      the wild-type control. Haem is still detected in the isolated PSII supercomplexes
      but at sub-stoichiometric levels consistent with weaker binding to the mutated
      cytochrome. Analysis of PSII activity in cells indicates slowed electron transfer
      in the mutant between plastoquinones QA and QB. We show that PSII activity in the
      mutant is more sensitive to chronic photoinhibition than the WT control because
      of two effects: a faster rate of damage and an impaired PSII repair cycle at the
      level of synthesis and/or incorporation of D1 into PSII. We also demonstrate that
      Cyt b-559 plays a role during the critical stage of assembling the Mn4CaO5
      cluster. Overall we conclude that Cyt b-559 optimises electron transfer on the
      acceptor side of PSII and plays physiologically important roles in the assembly,
      repair and maintenance of the complex. 

PMID- 24850840
TI  - Therapeutic efficacy of an Fc-enhanced TCR-like antibody to the intracellular WT1
      oncoprotein.
AB  - PURPOSE: RMFPNAPYL (RMF), a Wilms' tumor gene 1 (WT1)-derived CD8 T-cell epitope
      presented by HLA-A*02:01, is a validated target for T-cell-based immunotherapy.
      We previously reported ESK1, a high avidity (Kd < 0.2 nmol/L), fully-human
      monoclonal antibody (mAb) specific for the WT1 RMF peptide/HLA-A*02:01 complex,
      which selectively bound and killed WT1(+) and HLA-A*02:01(+) leukemia and solid
      tumor cell lines. EXPERIMENTAL DESIGN: We engineered a second-generation mAb,
      ESKM, to have enhanced antibody-dependent cell-mediated cytotoxicity (ADCC)
      function due to altered Fc glycosylation. ESKM was compared with native ESK1 in
      binding assays, in vitro ADCC assays, and mesothelioma and leukemia therapeutic
      models and pharmacokinetic studies in mice. ESKM toxicity was assessed in HLA
      A*02:01(+) transgenic mice. RESULTS: ESK antibodies mediated ADCC against
      hematopoietic and solid tumor cells at concentrations below 1 MUg/mL, but ESKM
      was about 5- to 10-fold more potent in vitro against multiple cancer cell lines.
      ESKM was more potent in vivo against JMN mesothelioma, and effective against SET2
      AML and fresh ALL xenografts. ESKM had a shortened half-life (4.9 days vs. 6.5
      days), but an identical biodistribution pattern in C57BL/6J mice. At therapeutic
      doses of ESKM, there was no difference in half-life or biodistribution in HLA
      A*02:01(+) transgenic mice compared with the parent strain. Importantly,
      therapeutic doses of ESKM in these mice caused no depletion of total WBCs or
      hematopoetic stem cells, or pathologic tissue damage. CONCLUSIONS: The data
      provide proof of concept that an Fc-enhanced mAb can improve efficacy against a
      low-density, tumor-specific, peptide/MHC target, and support further development
      of this mAb against an important intracellular oncogenic protein.

PMID- 24850842
TI  - Prostate MRI: evaluating tumor volume and apparent diffusion coefficient as
      surrogate biomarkers for predicting tumor Gleason score.
AB  - PURPOSE: To investigate whether tumor volume derived from apparent diffusion
      coefficient (ADC) maps (VolumeADC) and tumor mean ADC value (ADCmean) are
      independent predictors of prostate tumor Gleason score (GS). EXPERIMENTAL DESIGN:
      Tumor volume and GS were recorded from whole-mount histopathology for 131 men
      (median age, 60 years) who underwent endorectal diffusion-weighted MRI for local
      staging of prostate cancer before prostatectomy. VolumeADC and ADCmean were
      derived from ADC maps and correlated with histopathologic tumor volume and GS.
      Univariate and multivariate analyses were performed to evaluate prediction of
      tumor aggressiveness. Areas under receiver-operating characteristics curves (AUC)
      were calculated to evaluate the performance of VolumeADC and ADCmean in
      discriminating tumors of GS 6 and GS >=7. RESULTS: Histopathology identified 116
      tumor foci >0.5 mL. VolumeADC correlated significantly with histopathologic tumor
      volume (rho = 0.683). The correlation increased with increasing GS (rho = 0.453
      for GS 6 tumors; rho = 0.643 for GS 7 tumors; rho = 0.980 for GS >=8 tumors).
      Both VolumeADC (rho = 0.286) and ADCmean (rho = -0.309) correlated with GS. At
      univariate analysis, both VolumeADC (P = 0.0325) and ADCmean (P = 0.0033) could
      differentiate GS = 6 from GS >=7 tumor foci. However, at multivariate analysis,
      only ADCmean (P = 0.0156) was a significant predictor of tumor aggressiveness
      (i.e., GS 6 vs. GS >=7). For differentiating GS 6 from GS >=7 tumors, AUCs were
      0.644 and 0.704 for VolumeADC and ADCmean, respectively, and 0.749 for both
      parameters combined. CONCLUSION: In patients with prostate cancer, ADCmean is an
      independent predictor of tumor aggressiveness, but VolumeADC is not. The latter
      parameter adds little to the ADCmean in predicting tumor GS.

PMID- 24850841
TI  - VEGF/VEGFR-2 upregulates EZH2 expression in lung adenocarcinoma cells and EZH2
      depletion enhances the response to platinum-based and VEGFR-2-targeted therapy.
AB  - PURPOSE: To investigate the mechanisms of regulation and role associated with
      enhancer of zeste homolog 2 (EZH2) expression in lung cancer cells. EXPERIMENTAL
      DESIGN: We investigated the mechanisms of EZH2 expression associated with the
      VEGF/VEGFR-2 pathway. Furthermore, we sought to determine the role of EZH2 in
      response of lung adenocarcinoma to platinum-based chemotherapy, as well as the
      effect of EZH2 depletion on VEGFR-2-targeted therapy in lung adenocarcinoma cell
      lines. In addition, we characterized EZH2 expression in lung adenocarcinoma
      specimens and correlated it with patients' clinical characteristics. RESULTS: In
      this study, we demonstrate that VEGF/VEGFR-2 activation induces expression of
      EZH2 through the upregulation of E2F3 and hypoxia-inducible factor-1alpha
      (HIF1alpha), and downregulated expression of miR-101. EZH2 depletion by treatment
      with 3-deazaneplanocin A and knockdown by siRNA decreased the expression of EZH2
      and H3K27me3, increased PARP-C level, reduced cell proliferation and migration,
      and increased sensitivity of the cells to treatment with cisplatin and
      carboplatin. In addition, high EZH2 expression was associated with poor overall
      survival in patients who received platinum-based adjuvant therapy, but not in
      patients who did not receive this therapy. Furthermore, we demonstrated for the
      first time that the inhibition of EZH2 greatly increased the sensitivity of lung
      adenocarcinoma cells to the anti-VEGFR-2 drug AZD2171. CONCLUSION: Our results
      suggest that the VEGF/VEGFR-2 pathway plays a role in regulation of EZH2
      expression via E2F3, HIF1alpha, and miR-101. EZH2 depletion decreases the
      malignant potential of lung adenocarcinoma and sensitivity of the cells to both
      platinum-based and VEGFR-2-targeted therapy.

PMID- 24850843
TI  - FGFR1/3 tyrosine kinase fusions define a unique molecular subtype of non-small
      cell lung cancer.
AB  - PURPOSE: The fibroblast growth factor receptor (FGFR)-3 fusion genes have been
      recently demonstrated in a subset of non-small cell lung cancer (NSCLC). To aid
      in identification and treatment of these patients, we examined the frequency,
      clinicopathologic characteristics, and treatment outcomes of patients who had
      NSCLC with or without FGFR fusions. EXPERIMENTAL DESIGN: Fourteen known FGFR
      fusion variants, including FGFR1, FGFR2, and FGFR3, were detected by RT-PCR and
      verified by direct sequencing in 1,328 patients with NSCLC. All patients were
      also analyzed for mutations in EGFR, KRAS, HER2, BRAF, ALK, RET, and ROS1.
      Clinical characteristics, including age, sex, smoking status, stage, subtypes of
      lung adenocarcinoma, relapse-free survival, and overall survival, were collected.
      RESULTS: Of 1,328 tumors screened, two (0.2%) were BAG4-FGFR1 fusion and 15
      (1.1%) were FGFR3-TACC3 fusion. Six of 1,016 patients with lung adenocarcinoma
      were FGFR3-TACC3 fusions and 11 of 312 lung squamous cell carcinoma harbored BAG4
      FGFR1 or FGFR3-TACC3 fusions. Compared with the FGFR fusion-negative group,
      patients with FGFR fusions were more likely to be smokers (94.1%, 16 of 17
      patients, P < 0.001), significantly associated with larger tumor (>3 cm; 88.2%,
      15 of 17 patients, P < 0.001) and with a tendency to be more poorly
      differentiated (53.9%, nine of 17 patients, P = 0.095). CONCLUSIONS: FGFR fusions
      define a molecular subset of NSCLC with distinct clinical characteristics. FGFR
      is a druggable target and patients with FGFR fusions may benefit from FGFR
      targeted therapy, which needs further clinical investigation.

PMID- 24850844
TI  - Real-time immune monitoring to guide plasmid DNA vaccination schedule targeting
      prostatic acid phosphatase in patients with castration-resistant prostate cancer.
AB  - PURPOSE: We have previously reported that a DNA vaccine encoding prostatic acid
      phosphatase (PAP) could elicit PAP-specific T cells in patients with early
      recurrent prostate cancer. In the current pilot trial, we sought to evaluate
      whether prolonged immunization with regular booster immunizations, or
      "personalized" schedules of immunization determined using real-time immune
      monitoring, could elicit persistent, antigen-specific T cells, and whether
      treatment was associated with changes in PSA doubling time (PSA DT). EXPERIMENTAL
      DESIGN: Sixteen patients with castration-resistant, nonmetastatic prostate cancer
      received six immunizations at 2-week intervals and then either quarterly (arm 1)
      or as determined by multiparameter immune monitoring (arm 2). RESULTS: Patients
      were on study a median of 16 months; four received 24 vaccinations. Only one
      event associated with treatment >grade 2 was observed. Six of 16 (38%) remained
      metastasis-free at 2 years. PAP-specific T cells were elicited in 12 of 16 (75%),
      predominantly of a Th1 phenotype, which persisted in frequency and phenotype for
      at least 1 year. IFNgamma-secreting T-cell responses measured by ELISPOT were
      detectable in 5 of 13 individuals at 1 year, and this was not statistically
      different between study arms. The overall median fold change in PSA DT from
      pretreatment to posttreatment was 1.6 (range, 0.6-7.0; P = 0.036). CONCLUSIONS:
      Repetitive immunization with a plasmid DNA vaccine was safe and elicited Th1
      biased antigen-specific T cells that persisted over time. Modifications in the
      immunization schedule based on real-time immune monitoring did not increase the
      frequency of patients developing effector and memory T-cell responses with this
      DNA vaccine.

PMID- 24850845
TI  - A high-affinity, high-stability photoacoustic agent for imaging gastrin-releasing
      peptide receptor in prostate cancer.
AB  - PURPOSE: To evaluate the utility of targeted photoacoustic imaging (PAI) in
      providing molecular information to complement intrinsic functional and anatomical
      details of the vasculature within prostate lesion. EXPERIMENTAL DESIGN: We
      developed a PAI agent, AA3G-740, that targets gastrin-releasing peptide receptor
      (GRPR), found to be highly overexpressed in prostate cancer. The binding
      specificity of the agent was evaluated in human prostate cancer cell lines, PC3
      and LNCaP, and antagonist properties determined by cell internalization and
      intracellular calcium mobilization studies. The imaging sensitivity was assessed
      for the agent itself and for the PC3 cells labeled with agent. The in vivo
      stability of the agent was determined in human plasma and in the blood of living
      mice. The in vivo binding of the agent was evaluated in PC3 prostate tumor models
      in mice, and was validated ex vivo by optical imaging. RESULTS: AA3G-740
      demonstrated strong and specific binding to GRPR. The sensitivity of detection in
      vitro indicated suitability of the agent to image very small lesions. In mice,
      the agent was able to bind to GRPR even in poorly vascularized tumors leading to
      nearly 2-fold difference in photoacoustic signal relative to the control agent.
      CONCLUSIONS: The ability to image both vasculature and molecular profile outside
      the blood vessels gives molecular PAI a unique advantage over currently used
      imaging techniques. The imaging method presented here can find application both
      in diagnosis and in image-guided biopsy.

PMID- 24850847
TI  - Semi-mechanistic pharmacokinetic/pharmacodynamic modeling of the antitumor
      activity of LY2835219, a new cyclin-dependent kinase 4/6 inhibitor, in mice
      bearing human tumor xenografts.
AB  - PURPOSE: Selective inhibition of cyclin-dependent kinases 4 and 6 (CDK4/6)
      represents a promising therapeutic strategy. However, despite documented evidence
      of clinical activity, limited information is available on the optimal dosing
      strategy of CDK4/6 inhibitors. Here, we present an integrated semi-mechanistic
      pharmacokinetic/pharmacodynamic model to characterize the quantitative
      pharmacology of LY2835219, a CDK4/6 inhibitor, in xenograft tumors. EXPERIMENTAL
      DESIGN: LY2835219 plasma concentrations were connected to CDK4/6 inhibition and
      cell-cycle arrest in colo-205 human colorectal xenografts by incorporating the
      biomarkers, phospho-(ser780)-Rb, topoisomerase II alpha, and phosphohistone H3,
      into a precursor-dependent transit compartment model. This biomarker model was
      then connected to tumor growth inhibition (TGI) by: (i) relating the rate of
      tumor growth to mitotic cell density, and (ii) incorporating a concentration
      dependent mixed cytostatic/cytotoxic effect driving quiescence and cell death at
      high doses. Model validation was evaluated by predicting LY2835219-mediated
      antitumor effect in A375 human melanoma xenografts. RESULTS: The model
      successfully described LY2835219-mediated CDK4/6 inhibition, cell-cycle arrest,
      and TGI in colo-205, and was validated in A375. The model also demonstrated that
      a chronic dosing strategy achieving minimum steady-state trough plasma
      concentrations of 200 ng/mL is required to maintain durable cell-cycle arrest.
      Quiescence and cell death can be induced by further increasing LY2835219 plasma
      concentrations. CONCLUSIONS: Our model provides mechanistic insight into the
      quantitative pharmacology of LY2835219 and supports the therapeutic dose and
      chronic dosing strategy currently adopted in clinical studies.

PMID- 24850846
TI  - Ectopic expression of cancer-testis antigens in cutaneous T-cell lymphoma
      patients.
AB  - PURPOSE: The pathogenesis of cutaneous T-cell lymphoma (CTCL) remains only
      partially understood. A number of recent studies attempted to identify novel
      diagnostic markers and future therapeutic targets. One group of antigens, cancer
      testis (CT) antigens, normally present solely in testicular germ cells, can be
      ectopically expressed in a variety of cancers. Currently, only a few studies
      attempted to investigate the expression of CT antigens in CTCL. EXPERIMENTAL
      DESIGN: In the present work, we test the expression of CT genes in a cohort of
      patients with CTCL, normal skin samples, skin from benign inflammatory
      dermatoses, and in patient-derived CTCL cells. We correlate such expression with
      the p53 status and explore molecular mechanisms behind their ectopic expression
      in these cells. RESULTS: Our findings demonstrate that SYCP1, SYCP3, REC8, SPO11,
      and GTSF1 genes are heterogeneously expressed in patients with CTCL and patient
      derived cell lines, whereas cTAGE1 (cutaneous T-cell lymphoma-associated antigen
      1) was found to be robustly expressed in both. Mutated p53 status did not appear
      to be a requirement for the ectopic expression of CT antigens. While T-cell
      stimulation resulted in a significant upregulation of STAT3 and JUNB expression,
      it did not significantly alter the expression of CT antigens. Treatment of CTCL
      cells in vitro with vorinostat or romidepsin histone deacetylase inhibitors
      resulted in a significant dose-dependent upregulation of mRNA but not protein.
      Further expression analysis demonstrated that SYCP1, cTAGE1, and GTSF1 were
      expressed in CTCL, but not in normal skin or benign inflammatory dermatoses.
      CONCLUSIONS: A number of CT genes are ectopically expressed in patients with CTCL
      and can be used as biomarkers or novel targets for immunotherapy.

PMID- 24850848
TI  - iSimp in BioC standard format: enhancing the interoperability of a sentence
      simplification system.
AB  - This article reports the use of the BioC standard format in our sentence
      simplification system, iSimp, and demonstrates its general utility. iSimp is
      designed to simplify complex sentences commonly found in the biomedical text, and
      has been shown to improve existing text mining applications that rely on the
      analysis of sentence structures. By adopting the BioC format, we aim to make
      iSimp readily interoperable with other applications in the biomedical domain. To
      examine the utility of iSimp in BioC, we implemented a rule-based relation
      extraction system that uses iSimp as a preprocessing module and BioC for data
      exchange. Evaluation on the training corpus of BioNLP-ST 2011 GENIA Event
      Extraction (GE) task showed that iSimp sentence simplification improved the
      recall by 3.2% without reducing precision. The iSimp simplification-annotated
      corpora, both our previously used corpus and the GE corpus in the current study,
      have been converted into the BioC format and made publicly available at the
      project's Web site: http://research.bioinformatics.udel.edu/isimp/. Database
      URL:http://research.bioinformatics.udel.edu/isimp/ 

PMID- 24850849
TI  - The Stem Cell Niche in Leaf Axils Is Established by Auxin and Cytokinin in
      Arabidopsis.
AB  - Plants differ from most animals in their ability to initiate new cycles of growth
      and development, which relies on the establishment and activity of branch
      meristems harboring new stem cell niches. In seed plants, this is achieved by
      axillary meristems, which are established in the axil of each leaf base and
      develop into lateral branches. Here, we describe the initial processes of
      Arabidopsis thaliana axillary meristem initiation. Using reporter gene expression
      analysis, we find that axillary meristems initiate from leaf axil cells with low
      auxin through stereotypical stages. Consistent with this, ectopic overproduction
      of auxin in the leaf axil efficiently inhibits axillary meristem initiation.
      Furthermore, our results demonstrate that auxin efflux is required for the leaf
      axil auxin minimum and axillary meristem initiation. After lowering of auxin
      levels, a subsequent cytokinin signaling pulse is observed prior to axillary
      meristem initiation. Genetic analysis suggests that cytokinin perception and
      signaling are both required for axillary meristem initiation. Finally, we show
      that cytokinin overproduction in the leaf axil partially rescue axillary meristem
      initiation-deficient mutants. These results define a mechanistic framework for
      understanding axillary meristem initiation.

PMID- 24850850
TI  - Decreased Nucleotide and Expression Diversity and Modified Coexpression Patterns
      Characterize Domestication in the Common Bean.
AB  - Using RNA sequencing technology and de novo transcriptome assembly, we compared
      representative sets of wild and domesticated accessions of common bean (Phaseolus
      vulgaris) from Mesoamerica. RNA was extracted at the first true-leaf stage, and
      de novo assembly was used to develop a reference transcriptome; the final data
      set consists of ~190,000 single nucleotide polymorphisms from 27,243 contigs in
      expressed genomic regions. A drastic reduction in nucleotide diversity (~60%) is
      evident for the domesticated form, compared with the wild form, and almost 50% of
      the contigs that are polymorphic were brought to fixation by domestication. In
      parallel, the effects of domestication decreased the diversity of gene expression
      (18%). While the coexpression networks for the wild and domesticated accessions
      demonstrate similar seminal network properties, they show distinct community
      structures that are enriched for different molecular functions. After simulating
      the demographic dynamics during domestication, we found that 9% of the genes were
      actively selected during domestication. We also show that selection induced a
      further reduction in the diversity of gene expression (26%) and was associated
      with 5-fold enrichment of differentially expressed genes. While there is
      substantial evidence of positive selection associated with domestication, in a
      few cases, this selection has increased the nucleotide diversity in the
      domesticated pool at target loci associated with abiotic stress responses,
      flowering time, and morphology.

PMID- 24850851
TI  - Auxin Depletion from the Leaf Axil Conditions Competence for Axillary Meristem
      Formation in Arabidopsis and Tomato.
AB  - The enormous variation in architecture of flowering plants is based to a large
      extent on their ability to form new axes of growth throughout their life span.
      Secondary growth is initiated from groups of pluripotent cells, called meristems,
      which are established in the axils of leaves. Such meristems form lateral organs
      and develop into a side shoot or a flower, depending on the developmental status
      of the plant and environmental conditions. The phytohormone auxin is well known
      to play an important role in inhibiting the outgrowth of axillary buds, a
      phenomenon known as apical dominance. However, the role of auxin in the process
      of axillary meristem formation is largely unknown. In this study, we show in the
      model species Arabidopsis thaliana and tomato (Solanum lycopersicum) that auxin
      is depleted from leaf axils during vegetative development. Disruption of polar
      auxin transport compromises auxin depletion from the leaf axil and axillary
      meristem initiation. Ectopic auxin biosynthesis in leaf axils interferes with
      axillary meristem formation, whereas repression of auxin signaling in polar auxin
      transport mutants can largely rescue their branching defects. These results
      strongly suggest that depletion of auxin from leaf axils is a prerequisite for
      axillary meristem formation during vegetative development.

PMID- 24850852
TI  - Colletotrichum orbiculare Secretes Virulence Effectors to a Biotrophic Interface
      at the Primary Hyphal Neck via Exocytosis Coupled with SEC22-Mediated Traffic.
AB  - The hemibiotrophic pathogen Colletotrichum orbiculare develops biotrophic hyphae
      inside cucumber (Cucumis sativus) cells via appressorial penetration; later, the
      pathogen switches to necrotrophy. C. orbiculare also expresses specific effectors
      at different stages. Here, we found that virulence-related effectors of C.
      orbiculare accumulate in a pathogen-host biotrophic interface. Fluorescence
      tagged effectors accumulated in a ring-like region around the neck of the
      biotrophic primary hyphae. Fluorescence imaging of cellular components and
      transmission electron microscopy showed that the ring-like signals of the
      effectors localized at the pathogen-plant interface. Effector accumulation at the
      interface required induction of its expression during the early biotrophic phase,
      suggesting that transcriptional regulation may link to effector localization. We
      also investigated the route of effector secretion to the interface. An exocytosis
      related component, the Rab GTPase SEC4, localized to the necks of biotrophic
      primary hyphae adjacent to the interface, thereby suggesting focal effector
      secretion. Disruption of SEC4 in C. orbiculare reduced virulence and impaired
      effector delivery to the ring signal interface. Disruption of the v-SNARE SEC22
      also reduced effector delivery. These findings suggest that biotrophy-expressed
      effectors are secreted, via the endoplasmic reticulum-to-Golgi route and
      subsequent exocytosis, toward the interface generated between C. orbiculare and
      the host cell.

PMID- 24850853
TI  - Endoreduplication-mediated initiation of symbiotic organ development in Lotus
      japonicus.
AB  - Many leguminous plants have a unique ability to reset and alter the fate of
      differentiated root cortical cells to form new organs of nitrogen-fixing root
      nodules during legume-Rhizobium symbiosis. Recent genetic studies on the role of
      cytokinin signaling reveal that activation of cytokinin signaling is crucial to
      the nodule organogenesis process. However, the genetic mechanism underlying the
      initiation of nodule organogenesis is poorly understood due to the low number of
      genes that have been identified. Here, we have identified a novel nodulation
      deficient mutant named vagrant infection thread 1 (vag1) after suppressor mutant
      screening of spontaneous nodule formation 2, a cytokinin receptor gain-of
      function mutant in Lotus japonicus. The VAG1 gene encodes a protein that is
      putatively orthologous to Arabidopsis ROOT HAIRLESS 1/HYPOCOTYL 7, a component of
      the plant DNA topoisomerase VI that is involved in the control of
      endoreduplication. Nodule phenotype of the vag1 mutant shows that VAG1 is
      required for the ploidy-dependent cell growth of rhizobial-infected cells.
      Furthermore, VAG1 mediates the onset of endoreduplication in cortical cells
      during early nodule development, which may be essential for the initiation of
      cortical cell proliferation that leads to nodule primordium formation. In
      addition, cortical infection is severely impaired in the vag1 mutants, whereas
      the epidermal infection threads formation is normal. This suggests that the VAG1
      mediated endoreduplication of cortical cells may be required for the guidance of
      symbiotic bacteria to host meristematic cells.

PMID- 24850854
TI  - MetaImprint: an information repository of mammalian imprinted genes.
AB  - Genomic imprinting is a complex genetic and epigenetic phenomenon that plays
      important roles in mammalian development and diseases. Mammalian imprinted genes
      have been identified widely by experimental strategies or predicted using
      computational methods. Systematic information for these genes would be necessary
      for the identification of novel imprinted genes and the analysis of their
      regulatory mechanisms and functions. Here, a well-designed information
      repository, MetaImprint (http://bioinfo.hrbmu.edu.cn/MetaImprint), is presented,
      which focuses on the collection of information concerning mammalian imprinted
      genes. The current version of MetaImprint incorporates 539 imprinted genes,
      including 255 experimentally confirmed genes, and their detailed research courses
      from eight mammalian species. MetaImprint also hosts genome-wide genetic and
      epigenetic information of imprinted genes, including imprinting control regions,
      single nucleotide polymorphisms, non-coding RNAs, DNA methylation and histone
      modifications. Information related to human diseases and functional annotation
      was also integrated into MetaImprint. To facilitate data extraction, MetaImprint
      supports multiple search options, such as by gene ID and disease name. Moreover,
      a configurable Imprinted Gene Browser was developed to visualize the information
      on imprinted genes in a genomic context. In addition, an Epigenetic Changes
      Analysis Tool is provided for online analysis of DNA methylation and histone
      modification differences of imprinted genes among multiple tissues and cell
      types. MetaImprint provides a comprehensive information repository of imprinted
      genes, allowing researchers to investigate systematically the genetic and
      epigenetic regulatory mechanisms of imprinted genes and their functions in
      development and diseases.

PMID- 24850855
TI  - A crucial role for the ubiquitously expressed transcription factor Sp1 at early
      stages of hematopoietic specification.
AB  - Mammalian development is regulated by the interplay of tissue-specific and
      ubiquitously expressed transcription factors, such as Sp1. Sp1 knockout mice die
      in utero with multiple phenotypic aberrations, but the underlying molecular
      mechanism of this differentiation failure has been elusive. Here, we have used
      conditional knockout mice as well as the differentiation of mouse ES cells as a
      model with which to address this issue. To this end, we examined differentiation
      potential, global gene expression patterns and Sp1 target regions in Sp1 wild
      type and Sp1-deficient cells representing different stages of hematopoiesis. Sp1(
      /-) cells progress through most embryonic stages of blood cell development but
      cannot complete terminal differentiation. This failure to fully differentiate is
      not seen when Sp1 is knocked out at later developmental stages. For most Sp1
      target and non-target genes, gene expression is unaffected by Sp1 inactivation.
      However, Cdx genes and multiple Hox genes are stage-specific targets of Sp1 and
      are downregulated at an early stage. As a consequence, expression of genes
      involved in hematopoietic specification is progressively deregulated. Our work
      demonstrates that the early absence of active Sp1 sets a cascade in motion that
      culminates in a failure of terminal hematopoietic differentiation and emphasizes
      the role of ubiquitously expressed transcription factors for tissue-specific gene
      regulation. In addition, our global side-by-side analysis of the response of the
      transcriptional network to perturbation sheds a new light on the regulatory
      hierarchy of hematopoietic specification.

PMID- 24850856
TI  - DNMT3L promotes quiescence in postnatal spermatogonial progenitor cells.
AB  - The ability of adult stem cells to reside in a quiescent state is crucial for
      preventing premature exhaustion of the stem cell pool. However, the intrinsic
      epigenetic factors that regulate spermatogonial stem cell quiescence are largely
      unknown. Here, we investigate in mice how DNA methyltransferase 3-like (DNMT3L),
      an epigenetic regulator important for interpreting chromatin context and
      facilitating de novo DNA methylation, sustains the long-term male germ cell pool.
      We demonstrated that stem cell-enriched THY1(+) spermatogonial stem/progenitor
      cells (SPCs) constituted a DNMT3L-expressing population in postnatal testes.
      DNMT3L influenced the stability of promyelocytic leukemia zinc finger (PLZF),
      potentially by downregulating Cdk2/CDK2 expression, which sequestered CDK2
      mediated PLZF degradation. Reduced PLZF in Dnmt3l KO THY1(+) cells released its
      antagonist, Sal-like protein 4A (SALL4A), which is associated with overactivated
      ERK and AKT signaling cascades. Furthermore, DNMT3L was required to suppress the
      cell proliferation-promoting factor SALL4B in THY1(+) SPCs and to prevent
      premature stem cell exhaustion. Our results indicate that DNMT3L is required to
      delicately balance the cycling and quiescence of SPCs. These findings reveal a
      novel role for DNMT3L in modulating postnatal SPC cell fate decisions.

PMID- 24850857
TI  - A dynamic regulatory network explains ParaHox gene control of gut patterning in
      the sea urchin.
AB  - The anteroposterior patterning of the embryonic gut represents one of the most
      intriguing biological processes in development. A dynamic control of gene
      transcription regulation and cell movement is perfectly orchestrated to shape a
      functional gut in distinct specialized parts. Two ParaHox genes, Xlox and Cdx,
      play key roles in vertebrate and sea urchin gut patterning through molecular
      mechanisms that are still mostly unclear. Here, we have combined functional
      analysis methodologies with high-resolution imaging and RNA-seq to investigate
      Xlox and Cdx regulation and function. We reveal part of the regulatory machinery
      responsible for the onset of Xlox and Cdx transcription, uncover a Wnt10 signal
      that mediates Xlox repression in the intestinal cells, and provide evidence of
      Xlox- and Cdx-mediated control of stomach and intestine differentiation,
      respectively. Our findings offer a novel mechanistic explanation of how the
      control of transcription is linked to cell differentiation and morphogenesis for
      the development of a perfectly organized biological system such as the sea urchin
      larval gut.

PMID- 24850858
TI  - Automated pipeline for anatomical phenotyping of mouse embryos using micro-CT.
AB  - The International Mouse Phenotyping Consortium (IMPC) plans to phenotype 20,000
      single-gene knockout mice to gain an insight into gene function. Approximately
      30% of these knockout mouse lines will be embryonic or perinatal lethal. The IMPC
      has selected three-dimensional (3D) imaging to phenotype these mouse lines at
      relevant stages of embryonic development in an attempt to discover the cause of
      lethality using detailed anatomical information. Rate of throughput is paramount
      as IMPC production centers have been given the ambitious task of completing this
      phenotyping project by 2021. Sifting through the wealth of data within high
      resolution 3D mouse embryo data sets by trained human experts is infeasible at
      this scale. Here, we present a phenotyping pipeline that identifies statistically
      significant anatomical differences in the knockout, in comparison with the wild
      type, through a computer-automated image registration algorithm. This phenotyping
      pipeline consists of three analyses (intensity, deformation, and atlas based)
      that can detect missing anatomical structures and differences in volume of whole
      organs as well as on the voxel level. This phenotyping pipeline was applied to
      micro-CT images of two perinatal lethal mouse lines: a hypomorphic mutation of
      the Tcf21 gene (Tcf21-hypo) and a knockout of the Satb2 gene. With the proposed
      pipeline we were able to identify the majority of morphological phenotypes
      previously published for both the Tcf21-hypo and Satb2 mutant mouse embryos in
      addition to novel phenotypes. This phenotyping pipeline is an unbiased, automated
      method that highlights only those structural abnormalities that survive
      statistical scrutiny and illustrates them in a straightforward fashion.

PMID- 24850860
TI  - The optimal lateral root branching density for maize depends on nitrogen and
      phosphorus availability.
AB  - Observed phenotypic variation in the lateral root branching density (LRBD) in
      maize (Zea mays) is large (1-41 cm(-1) major axis [i.e. brace, crown, seminal,
      and primary roots]), suggesting that LRBD has varying utility and tradeoffs in
      specific environments. Using the functional-structural plant model SimRoot, we
      simulated the three-dimensional development of maize root architectures with
      varying LRBD and quantified nitrate and phosphorus uptake, root competition, and
      whole-plant carbon balances in soils varying in the availability of these
      nutrients. Sparsely spaced (less than 7 branches cm(-1)), long laterals were
      optimal for nitrate acquisition, while densely spaced (more than 9 branches cm(
      1)), short laterals were optimal for phosphorus acquisition. The nitrate results
      are mostly explained by the strong competition between lateral roots for nitrate,
      which causes increasing LRBD to decrease the uptake per unit root length, while
      the carbon budgets of the plant do not permit greater total root length (i.e.
      individual roots in the high-LRBD plants stay shorter). Competition and carbon
      limitations for growth play less of a role for phosphorus uptake, and
      consequently increasing LRBD results in greater root length and uptake. We
      conclude that the optimal LRBD depends on the relative availability of nitrate (a
      mobile soil resource) and phosphorus (an immobile soil resource) and is greater
      in environments with greater carbon fixation. The median LRBD reported in several
      field screens was 6 branches cm(-1), suggesting that most genotypes have an LRBD
      that balances the acquisition of both nutrients. LRBD merits additional
      investigation as a potential breeding target for greater nutrient acquisition. 

PMID- 24850859
TI  - Evolution of the Phosphoenolpyruvate Carboxylase Protein Kinase Family in C3 and
      C4 Flaveria spp.
AB  - The key enzyme for C4 photosynthesis, Phosphoenolpyruvate Carboxylase (PEPC),
      evolved from nonphotosynthetic PEPC found in C3 ancestors. In all plants, PEPC is
      phosphorylated by Phosphoenolpyruvate Carboxylase Protein Kinase (PPCK). However,
      differences in the phosphorylation pattern exist among plants with these
      photosynthetic types, and it is still not clear if they are due to interspecies
      differences or depend on photosynthetic type. The genus Flaveria contains closely
      related C3, C3-C4 intermediate, and C4 species, which are evolutionarily young
      and thus well suited for comparative analysis. To characterize the evolutionary
      differences in PPCK between plants with C3 and C4 photosynthesis, transcriptome
      libraries from nine Flaveria spp. were used, and a two-member PPCK family (PPCKA
      and PPCKB) was identified. Sequence analysis identified a number of C3- and C4
      specific residues with various occurrences in the intermediates. Quantitative
      analysis of transcriptome data revealed that PPCKA and PPCKB exhibit inverse diel
      expression patterns and that C3 and C4 Flaveria spp. differ in the expression
      levels of these genes. PPCKA has maximal expression levels during the day,
      whereas PPCKB has maximal expression during the night. Phosphorylation patterns
      of PEPC varied among C3 and C4 Flaveria spp. too, with PEPC from the C4 species
      being predominantly phosphorylated throughout the day, while in the C3 species
      the phosphorylation level was maintained during the entire 24 h. Since C4
      Flaveria spp. evolved from C3 ancestors, this work links the evolutionary changes
      in sequence, PPCK expression, and phosphorylation pattern to an evolutionary
      phase shift of kinase activity from a C3 to a C4 mode.

PMID- 24850861
TI  - Feeling the hidden mechanical forces in lipid bilayer is an original sense.
AB  - Life's origin entails enclosing a compartment to hoard material, energy, and
      information. The envelope necessarily comprises amphipaths, such as prebiotic
      fatty acids, to partition the two aqueous domains. The self-assembled lipid
      bilayer comes with a set of properties including its strong anisotropic internal
      forces that are chemically or physically malleable. Added bilayer stretch can
      alter force vectors on embedded proteins to effect conformational change. The
      force-from-lipid principle was demonstrated 25 y ago when stretches opened
      purified Escherichia coli MscL channels reconstituted into artificial bilayers.
      This reductionistic exercise has rigorously been recapitulated recently with two
      vertebrate mechanosensitive K(+) channels (TREK1 and TRAAK). Membrane stretches
      have also been known to activate various voltage-, ligand-, or Ca(2+)-gated
      channels. Careful analyses showed that Kv, the canonical voltage-gated channel,
      is in fact exquisitely sensitive even to very small tension. In an unexpected
      context, the canonical transient-receptor-potential channels in the Drosophila
      eye, long presumed to open by ligand binding, is apparently opened by membrane
      force due to PIP2 hydrolysis-induced changes in bilayer strain. Being the
      intimate medium, lipids govern membrane proteins by physics as well as chemistry.
      This principle should not be a surprise because it parallels water's paramount
      role in the structure and function of soluble proteins. Today, overt or covert
      mechanical forces govern cell biological processes and produce sensations. At the
      genesis, a bilayer's response to osmotic force is likely among the first senses
      to deal with the capricious primordial sea. 

PMID- 24850862
TI  - Cbfbeta deletion in mice recapitulates cleidocranial dysplasia and reveals
      multiple functions of Cbfbeta required for skeletal development.
AB  - The pathogenesis of cleidocranial dysplasia (CCD) as well as the specific role of
      core binding factor beta (Cbfbeta) and the Runt-related transcription factor
      (RUNX)/Cbfbeta complex in postnatal skeletogenesis remain unclear. We demonstrate
      that Cbfbeta ablation in osteoblast precursors, differentiating chondrocytes,
      osteoblasts, and odontoblasts via Osterix-Cre, results in severe craniofacial
      dysplasia, skeletal dysplasia, abnormal teeth, and a phenotype recapitulating the
      clinical features of CCD. Cbfbeta(f/f)Osterix-Cre mice have fewer proliferative
      and hypertrophic chondrocytes, fewer osteoblasts, and almost absent trabecular
      bone, indicating that Cbfbeta may maintain trabecular bone formation through its
      function in hypertrophic chondrocytes and osteoblasts. Cbfbeta(f/f)Collagen, type
      1, alpha 1 (Col1alpha1)-Cre mice show decreased bone mineralization and skeletal
      deformities, but no radical deformities in teeth, mandibles, or cartilage,
      indicating that osteoblast lineage-specific ablation of Cbfbeta results in milder
      bone defects and less resemblance to CCD. Activating transcription factor 4
      (Atf4) and Osterix protein levels in both mutant mice are dramatically reduced.
      ChIP assays show that Cbfbeta directly associates with the promoter regions of
      Atf4 and Osterix. Our data further demonstrate that Cbfbeta highly up-regulates
      the expression of Atf4 at the transcriptional regulation level. Overall, our
      genetic dissection approach revealed that Cbfbeta plays an indispensable role in
      postnatal skeletal development and homeostasis in various skeletal cell types, at
      least partially by up-regulating the expression of Atf4 and Osterix. It also
      revealed that CCD may result from functional defects of the Runx2/Cbfbeta
      heterodimeric complex in various skeletal cells. These insights into the role of
      Cbfbeta in postnatal skeletogenesis and CCD pathogenesis may assist in the
      development of new therapies for CCD and osteoporosis. 

PMID- 24850863
TI  - Prokaryotic NavMs channel as a structural and functional model for eukaryotic
      sodium channel antagonism.
AB  - Voltage-gated sodium channels are important targets for the development of
      pharmaceutical drugs, because mutations in different human sodium channel
      isoforms have causal relationships with a range of neurological and
      cardiovascular diseases. In this study, functional electrophysiological studies
      show that the prokaryotic sodium channel from Magnetococcus marinus (NavMs) binds
      and is inhibited by eukaryotic sodium channel blockers in a manner similar to the
      human Nav1.1 channel, despite millions of years of divergent evolution between
      the two types of channels. Crystal complexes of the NavMs pore with several
      brominated blocker compounds depict a common antagonist binding site in the
      cavity, adjacent to lipid-facing fenestrations proposed to be the portals for
      drug entry. In silico docking studies indicate the full extent of the blocker
      binding site, and electrophysiology studies of NavMs channels with mutations at
      adjacent residues validate the location. These results suggest that the NavMs
      channel can be a valuable tool for screening and rational design of human drugs. 

PMID- 24850864
TI  - Combining linkage and association mapping identifies RECEPTOR-LIKE PROTEIN
      KINASE1 as an essential Arabidopsis shoot regeneration gene.
AB  - De novo shoot organogenesis (i.e., the regeneration of shoots on nonmeristematic
      tissue) is widely applied in plant biotechnology. However, the capacity to
      regenerate shoots varies highly among plant species and cultivars, and the
      factors underlying it are still poorly understood. Here, we evaluated the shoot
      regeneration capacity of 88 Arabidopsis thaliana accessions and found that the
      process is blocked at different stages in different accessions. We show that the
      variation in regeneration capacity between the Arabidopsis accessions Nok-3 and
      Ga-0 is determined by five quantitative trait loci (QTL): REG-1 to REG-5. Fine
      mapping by local association analysis identified RECEPTOR-LIKE PROTEIN KINASE1
      (RPK1), an abscisic acid-related receptor, as the most likely gene underlying REG
      1, which was confirmed by quantitative failure of an RPK1 mutation to complement
      the high and low REG-1 QTL alleles. The importance of RPK1 in regeneration was
      further corroborated by mutant and expression analysis. Altogether, our results
      show that association mapping combined with linkage mapping is a powerful method
      to discover important genes implicated in a biological process as complex as
      shoot regeneration. 

PMID- 24850865
TI  - Molecular-crowding effects on single-molecule RNA folding/unfolding
      thermodynamics and kinetics.
AB  - The effects of "molecular crowding" on elementary biochemical processes due to
      high solute concentrations are poorly understood and yet clearly essential to the
      folding of nucleic acids and proteins into correct, native structures. The
      present work presents, to our knowledge, first results on the single-molecule
      kinetics of solute molecular crowding, specifically focusing on GAAA tetraloop
      receptor folding to isolate a single RNA tertiary interaction using time
      correlated single-photon counting and confocal single-molecule FRET microscopy.
      The impact of crowding by high-molecular-weight polyethylene glycol on the RNA
      folding thermodynamics is dramatic, with up to DeltaDeltaG degrees  ~ -2.5
      kcal/mol changes in free energy and thus >60-fold increase in the folding
      equilibrium constant (Keq) for excluded volume fractions of 15%. Most
      importantly, time-correlated single-molecule methods permit crowding effects on
      the kinetics of RNA folding/unfolding to be explored for the first time (to our
      knowledge), which reveal that this large jump in Keq is dominated by a 35-fold
      increase in tetraloop-receptor folding rate, with only a modest decrease in the
      corresponding unfolding rate. This is further explored with temperature-dependent
      single-molecule RNA folding measurements, which identify that crowding effects
      are dominated by entropic rather than enthalpic contributions to the overall free
      energy change. Finally, a simple "hard-sphere" treatment of the solute excluded
      volume is invoked to model the observed kinetic trends, and which predict
      DeltaDeltaG degrees  ~ -5 kcal/mol free-energy stabilization at excluded volume
      fractions of 30%. 

PMID- 24850866
TI  - Generation of bright isolated attosecond soft X-ray pulses driven by multicycle
      midinfrared lasers.
AB  - High harmonic generation driven by femtosecond lasers makes it possible to
      capture the fastest dynamics in molecules and materials. However, to date the
      shortest subfemtosecond (attosecond, 10(-18) s) pulses have been produced only in
      the extreme UV region of the spectrum below 100 eV, which limits the range of
      materials and molecular systems that can be explored. Here we experimentally
      demonstrate a remarkable convergence of physics: when midinfrared lasers are used
      to drive high harmonic generation, the conditions for optimal bright, soft X-ray
      generation naturally coincide with the generation of isolated attosecond pulses.
      The temporal window over which phase matching occurs shrinks rapidly with
      increasing driving laser wavelength, to the extent that bright isolated
      attosecond pulses are the norm for 2-um driving lasers. Harnessing this
      realization, we experimentally demonstrate the generation of isolated soft X-ray
      attosecond pulses at photon energies up to 180 eV for the first time, to our
      knowledge, with a transform limit of 35 attoseconds (as), and a predicted linear
      chirp of 300 as. Most surprisingly, advanced theory shows that in contrast with
      as pulse generation in the extreme UV, long-duration, 10-cycle, driving laser
      pulses are required to generate isolated soft X-ray bursts efficiently, to
      mitigate group velocity walk-off between the laser and the X-ray fields that
      otherwise limit the conversion efficiency. Our work demonstrates a clear and
      straightforward approach for robustly generating bright isolated attosecond
      pulses of electromagnetic radiation throughout the soft X-ray region of the
      spectrum. 

PMID- 24850868
TI  - Phosphorylated AKT preserves stallion sperm viability and motility by inhibiting
      caspases 3 and 7.
AB  - AKT, also referred to as protein kinase B (PKB or RAC), plays a critical role in
      controlling cell survival and apoptosis. To gain insights into the mechanisms
      regulating sperm survival after ejaculation, the role of AKT was investigated in
      stallion spermatozoa using a specific inhibitor and a phosphoflow approach.
      Stallion spermatozoa were washed and incubated in Biggers-Whitten-Whittingham
      medium, supplemented with 1% polyvinyl alcohol (PVA) in the presence of 0
      (vehicle), 10, 20 or 30 MUM SH5, an AKT inhibitor. SH5 treatment reduced the
      percentage of sperm displaying AKT phosphorylation, with inhibition reaching a
      maximum after 1 h of incubation. This decrease in phosphorylation was
      attributable to either dephosphorylation or suppression of the active
      phosphorylation pathway. Stallion spermatozoa spontaneously dephosphorylated
      during in vitro incubation, resulting in a lack of a difference in AKT
      phosphorylation between the SH5-treated sperm and the control after 4 h of
      incubation. AKT inhibition decreased the proportion of motile spermatozoa (total
      and progressive) and the sperm velocity. Similarly, AKT inhibition reduced
      membrane integrity, leading to increased membrane permeability and reduced the
      mitochondrial membrane potential concomitantly with activation of caspases 3 and
      7. However, the percentage of spermatozoa exhibiting oxidative stress, the
      production of mitochondrial superoxide radicals, DNA oxidation and DNA
      fragmentation were not affected by AKT inhibition. It is concluded that AKT
      maintains the membrane integrity of ejaculated stallion spermatozoa, presumably
      by inhibiting caspases 3 and 7, which prevents the progression of spermatozoa to
      an incomplete form of apoptosis.

PMID- 24850867
TI  - Genomic landscape of CD34+ hematopoietic cells in myelodysplastic syndrome and
      gene mutation profiles as prognostic markers.
AB  - Myelodysplastic syndrome (MDS) includes a group of diseases characterized by
      dysplasia of bone marrow myeloid lineages with ineffective hematopoiesis and
      frequent evolution to acute myeloid leukemia (AML). Whole-genome sequencing was
      performed in CD34(+) hematopoietic stem/progenitor cells (HSPCs) from eight cases
      of refractory anemia with excess blasts (RAEB), the high-risk subtype of MDS. The
      nucleotide substitution patterns were found similar to those reported in AML, and
      mutations of 96 protein-coding genes were identified. Clonal architecture
      analysis revealed the presence of subclones in six of eight cases, whereas
      mutation detection of CD34(+) versus CD34(-) cells revealed heterogeneity of HSPC
      expansion status. With 39 marker genes belonging to eight functional categories,
      mutations were analyzed in 196 MDS cases including mostly RAEB (n = 89) and
      refractory cytopenia with multilineage dysplasia (RCMD) (n = 95). At least one
      gene mutation was detected in 91.0% of RAEB, contrary to that in RCMD (55.8%),
      suggesting a higher mutational burden in the former group. Gene abnormality
      patterns differed between MDS and AML, with mutations of activated signaling
      molecules and NPM1 being rare, whereas those of spliceosome more common, in MDS.
      Finally, gene mutation profiles also bore prognostic value in terms of overall
      survival and progression free survival. 

PMID- 24850869
TI  - Genetic variants of Fcgamma (GM allotypes) and the Fc-mediated effector functions
      in HIV-1 controllers.

PMID- 24850871
TI  - Single-step enrichment by Ti4+-IMAC and label-free quantitation enables in-depth
      monitoring of phosphorylation dynamics with high reproducibility and temporal
      resolution.
AB  - Quantitative phosphoproteomics workflows traditionally involve additional sample
      labeling and fractionation steps for accurate and in-depth analysis. Here we
      report a high-throughput, straightforward, and comprehensive label-free
      phosphoproteomics approach using the highly selective, reproducible, and
      sensitive Ti(4+)-IMAC phosphopeptide enrichment method. We demonstrate the
      applicability of this approach by monitoring the phosphoproteome dynamics of
      Jurkat T cells stimulated by prostaglandin E2 (PGE2) over six different time
      points, measuring in total 108 snapshots of the phosphoproteome. In total, we
      quantitatively monitored 12,799 unique phosphosites over all time points with
      very high quantitative reproducibility (average r > 0.9 over 100 measurements and
      a median cv < 0.2). PGE2 is known to increase cellular cAMP levels, thereby
      activating PKA. The in-depth analysis revealed temporal regulation of a wide
      variety of phosphosites associated not only with PKA, but also with a variety of
      other classes of kinases. Following PGE2 stimulation, several pathways became
      only transiently activated, revealing that in-depth dynamic profiling requires
      techniques with high temporal resolution. Moreover, the large publicly available
      dataset provides a valuable resource for downstream PGE2 signaling dynamics in T
      cells, and cAMP-mediated signaling in particular. More generally, our method
      enables in-depth, quantitative, high-throughput phosphoproteome screening on any
      system, requiring very little sample, sample preparation, and analysis time. 

PMID- 24850872
TI  - Ethics and end of life care: the Liverpool Care Pathway and the Neuberger Review.
AB  - The Liverpool Care Pathway for the Dying has recently been the topic of
      substantial media interest and also been subject to the independent Neuberger
      Review. This review has identified clear failings in some areas of care and
      recommended the Liverpool Care Pathway be phased out. I argue that while the
      evidence gathered of poor incidences of practice by the Review is of genuine
      concern for end of life care, the inferences drawn from this evidence are
      inconsistent with the causes for the concern. Seeking to end an approach that is
      widely seen as best practice and which can genuinely deliver high quality care
      because of negative impressions that have been formed from failing to implement
      it properly is not a good basis for radically overhauling our approach to end of
      life care. I conclude that improvements in training, communication and ethical
      decision-making, without the added demand to end the Liverpool Care Pathway,
      would have resulted in a genuine advance in end of life care. 

PMID- 24850873
TI  - Non-normative bodies, rationality, and legal personhood.
AB  - This article questions how legal personhood is constructed by law. Elective
      amputation is used as a way of interrogating the institutional, material, and
      discursive relations that combine in order to suspend legal personhood. Elective
      amputation is introduced in terms of medical and psychological explanations.
      Additionally, the perspective of self-identified elective amputees who choose to
      share their stories through online blogs is utilised to gain a narrative sense of
      how these individuals understand and engage with law. In particular, the areas of
      disability, sexuality, and rationality are used to exemplify law's continuing
      commitment to normative embodiment as grounds for ascribing legal personhood. 

PMID- 24850874
TI  - Novel photoplethysmography cardiovascular assessments in patients with Raynaud's
      phenomenon and systemic sclerosis: a pilot study.
AB  - OBJECTIVE: Multisite photoplethysmography (PPG) cardiovascular assessments can
      evaluate endothelial, peripheral autonomic and arterial dysfunction. The aim of
      this pilot study was to investigate the potential clinical utility of the
      technology in assessing patients with SSc and primary RP (PRP). METHODS:
      Multisite PPG pulse measurements, a reference ankle brachial pressure index
      (ABPI) and a full clinical assessment were undertaken for three subject groups:
      SSc, PRP and controls. Endothelial and autonomic function and arterial disease
      measures were obtained using pulse wave analysis. RESULTS: Nineteen SSc, 19 PRP
      and 23 control subjects were assessed and compared. Endothelial function was
      significantly impaired in SSc (P < 0.02), but with no difference between controls
      and PRP. Receiver operating characteristic-based classification accuracy was 81%
      (sensitivity 90%, specificity 74%) for separating SSc from controls and 82%
      (sensitivity 84%, specificity 79%) for separating SSc from PRP. SSc patients with
      digital ulcers had significantly lower endothelial function compared with those
      without ulcers (P < 0.05). Autonomic dysfunction was suggested in both SSc and
      PRP and was most exaggerated in patients with diffuse SSc. All groups had overall
      normal ABPI and arterial stiffness timing measures. Bilateral timing differences
      at the toes, which represents peripheral occlusive arterial disease, did show
      increased asymmetry in SSc (P < 0.02). CONCLUSION: Multisite PPG pulse technology
      showed potential diagnostic ability. By using measures of endothelial function,
      it differentiated SSc from control and PRP subjects with an accuracy of at least
      81%. Objective pulse-derived measures of autonomic function and arterial disease
      in SSc have also been reported in this pilot study.

PMID- 24850875
TI  - United Kingdom survey of current management of juvenile localized scleroderma.
AB  - OBJECTIVES: Juvenile localized scleroderma (JLS) is a rare condition that is
      often difficult to assess and for which a variety of monitoring tools have been
      described. We aimed to describe how monitoring tools are used and perceived by
      clinicians in the UK, to ascertain treatments used for JLS and to provide a
      description of transition arrangements to adult care. METHODS: An e-survey of UK
      paediatric rheumatologists and dermatologists managing children and young people
      (CYP) with JLS was distributed using the national organisations representing
      these clinician groups. We asked respondents for their views and experience using
      15 JLS monitoring tools, about transition services and about treatments used.
      RESULTS: Thirty-five dermatologists and 13 paediatric rheumatologists responded.
      Paediatric rheumatologists managed more CYP with JLS than dermatologists (median
      16-20 and 3, respectively). Transition arrangements were reported by 43% of
      dermatologists and 91% of paediatric rheumatologists. Medical photography was the
      most frequently regularly used monitoring tool (73% respondents). The modified
      Rodnan skin score was the skin score used most commonly: 33% of paediatric
      rheumatologists and 3% of dermatologists reported using this tool frequently.
      Topical treatments and ultraviolet light were used by 49-80% of dermatologists
      and 0-8% paediatric rheumatologists. Biologic drugs and CYC were used by 0-3% of
      dermatologists and 31-46% of paediatric rheumatologists. CONCLUSION: How
      monitoring tools are accessed, used and perceived by paediatric rheumatologists
      and dermatologists in the UK varies between and within clinician groups, as do
      treatment prescribing patterns and transition arrangements. These differences
      will impact on the feasibility of conducting multicentre clinical trials and on
      standardising clinical care.

PMID- 24850876
TI  - A study of erosive phenotypes in lupus arthritis using magnetic resonance imaging
      and anti-citrullinated protein antibody, anti-RA33 and RF autoantibody status.
AB  - OBJECTIVES: The aims of this study were to investigate the extent of MRI
      determined joint disease (erosion and synovitis) in SLE and to link this to
      autoantibody profiles known to be relevant to SLE, including ACPA, RF and anti
      RA33 antibodies. METHODS: Contrast-enhanced MRI of the hand and wrist was
      performed in 34 symptomatic SLE patients and in 15 RA patients with similar
      disease duration. Images were scored by two observers using the OMERACT
      rheumatoid arthritis MRI scoring (RAMRIS) system. Findings were correlated with
      clinical examination and autoantibody status. RESULTS: Erosions were present at
      the wrist in 93% of SLE patients and at the MCP joints in 61% of SLE patients.
      Despite the high prevalence of MRI-determined erosion, only 8.8% of SLE patients
      were ACPA positive, although these patients had a higher burden of erosive
      disease. There was no positive correlation with anti-RA33 titres and erosion
      scores in the SLE patients, but there was a negative correlation with anti-RA33
      titres and total bone oedema scores in the SLE patients. Ninety-three per cent of
      SLE patients had at least grade 1 synovitis at one or more MCP joints, and wrist
      joint synovitis was present in all the SLE patients. CONCLUSION: An MRI
      determined joint erosive phenotype is common in SLE, even in ACPA-negative cases.
      The conventional radiographic observation that anti-RA33 is not positively
      associated with erosion in patients with RA was also found to be the case in SLE
      patients.

PMID- 24850877
TI  - Correlations between changes in cytokines and clinical outcomes for early phase
      (proof of concept) trials in active diffuse systemic sclerosis using data from an
      imatinib study.
AB  - OBJECTIVE: Data from a small study testing imatinib to treat SSc were used to
      determine if cytokine changes were related to differences in clinical parameters
      to model future early phase trials pairing cytokine changes and clinical
      parameters. METHODS: Plasma and punch skin biopsy specimens collected at baseline
      and 6 months were analysed for levels of 26 fibrotic and inflammatory cytokines
      using multiplexed immunoassays and ELISA. Seven of nine patients on active
      treatment had paired data. Biopsies were biopulverized and standardized to
      protein levels in the tissue homogenate. Plasma was frozen at -80 degrees C and
      analysed using multiplexed immunoassays or ELISAs standardized to CRP.
      Correlations between fold changes in cytokines and differences in clinical
      parameters (skin score, physician and patient global assessments and HAQ) were
      performed. P < 0.01 was considered significant. RESULTS: After 6 months of
      imatinib treatment, plasma levels of soluble vascular cell adhesion molecule 1
      decreased significantly (P < 0.001), while tissue levels of soluble intercellular
      adhesion molecule 1 increased (P < 0.01). Some significant correlations between
      fold changes in certain plasma fibrotic and inflammatory cytokines and changes in
      clinical parameters after 6 months of treatment were found: patient global scores
      and IL-13 (r = 0.964, P < 0.0001); ESR and IL-12p70 (r = -0.903, P < 0.01); in
      tissue samples, patient global score and soluble E-selectin (r = 0.913, P <
      0.01); and physician global score with sCD40L (r = -0.883, P < 0.01). CONCLUSION:
      Some serum and tissue cytokines may have a role in early phase clinical trials of
      SSc, correlating with changes in clinical parameters. Serum and tissue samples
      could be analysed in early phase trials to determine whether they support the
      clinical observations. TRIAL REGISTRATION:
      http://clinicaltrials.gov/show/NCT01545427.

PMID- 24850878
TI  - Immune responses to stress in rheumatoid arthritis and psoriasis.
AB  - OBJECTIVE: Stress is one of the factors that may exacerbate the progression of
      chronic inflammatory diseases such as RA and psoriasis. We exploratively compared
      the effects of acute stress on levels of circulating cytokines involved in
      disease progression and/or the stress response in patients with RA, patients with
      psoriasis and healthy subjects. METHODS: Patients with RA, patients with
      psoriasis and healthy controls underwent a standardized psychosocial stress test
      (Trier Social Stress Test). Levels of circulating cytokines (IL-1beta, IL-2, IL
      4, IL-5, IL-6, IL-7, IL-8, IL-10, IFN-gamma and TNF-alpha) were measured before
      and after the stress test. RESULTS: The baseline levels of all cytokines, except
      IL-8, were significantly higher in patients with RA. After correction for
      baseline levels, patients with RA showed higher stress-induced levels of IL-1beta
      and IL-2 than patients with psoriasis and healthy controls. CONCLUSION: The
      results suggest that patients with RA have a different immune response to stress
      than patients with psoriasis or healthy controls. More needs to be learned about
      the complex interaction between stress, immune parameters and chronic
      inflammation.

PMID- 24850879
TI  - New pharmacological properties of Medicago sativa and Saponaria officinalis
      saponin-rich fractions addressed to Candida albicans.
AB  - The antifungal activity of the saponin-rich fractions (SFs) from Medicago sativa
      (aerial parts and roots) and Saponaria officinalis (used as a well-known source
      of plant saponins) against Candida albicans reference and clinical strains, their
      yeast-to-hyphal conversion, adhesion, and biofilm formation was investigated.
      Direct fungicidal/fungistatic properties of the tested phytochemicals used alone,
      as well as their synergy with azoles (probably resulting from yeast cell wall
      instability) were demonstrated. Here, to the best of our knowledge, we report for
      the first time the ability of saponin-rich extracts of M. sativa and S.
      officinalis to inhibit C. albicans germ tube formation, limit hyphal growth,
      reduce yeast adherence and biofilm formation, and eradicate mature (24 h) Candida
      biofilm. Moreover, M. sativa SFs (mainly obtained from aerial parts), in the
      range of concentrations which were active modulators of Candida virulence
      factors, exhibited low cytotoxicity against the mouse fibroblast line L929. These
      properties seem to be very promising in the context of using plant-derived SFs as
      potential novel antifungal therapeutics supporting classic drugs or as
      ingredients of disinfectants. 

PMID- 24850880
TI  - Instant screening and verification of carbapenemase activity in Bacteroides
      fragilis in positive blood culture, using matrix-assisted laser desorption
      ionization--time of flight mass spectrometry.
AB  - Rapid identification of isolates in positive blood cultures are of great
      importance to secure correct treatment of septicaemic patients. As antimicrobial
      resistance is increasing, rapid detection of resistance is crucial. Carbapenem
      resistance in Bacteroides fragilis associated with cfiA-encoded class B metallo
      beta-lactamase is emerging. In our study we spiked blood culture bottles with 26
      B. fragilis strains with various cfiA-status and ertapenem MICs. By using main
      spectra specific for cfiA-positive and cfiA-negative B. fragilis strains,
      isolates could be screened for resistance. To verify strains that were positive
      in the screening, a carbapenemase assay was performed where the specific peaks of
      intact and hydrolysed ertapenem were analysed with matrix-assisted laser
      desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). We show
      here that it is possible to correctly identify B. fragilis and to screen for
      enzymic carbapenem resistance directly from the pellet of positive blood
      cultures. The carbapenemase assay to verify the presence of the enzyme was
      successfully performed on the pellet from the direct identification despite the
      presence of blood components. The result of the procedure was achieved in 3 h.
      Also the Bruker mass spectrometric beta-lactamase assay (MSBL assay) prototype
      software was proven not only to be based on an algorithm that correlated with the
      manual inspection of the spectra, but also to improve the interpretation by
      showing the variation in the dataset. 

PMID- 24850881
TI  - First report of rhinosinusitis caused by Neoscytalidium dimidiatum in Iran.
AB  - The study describes isolation of Neoscytalidium dimidiatum from a case of
      eosinophilic fungal rhinosinusitis (EFRS). The isolate was identified by routine
      mycological methods and confirmed by DNA sequencing of the internal transcribed
      spacer (ITS) region of rDNA. To our knowledge, this is the first report of its
      kind from Iran. 

PMID- 24850882
TI  - Molecular analysis of low-level fluoroquinolone resistance in clinical isolates
      of Moraxella catarrhalis.
AB  - We investigated antimicrobial susceptibility and the molecular mechanism
      underlying low-level resistance to fluoroquinolones in 70 non-duplicate clinical
      isolates of Moraxella catarrhalis. The isolates were collected in a general
      hospital in Tokyo, Japan, between January and October 2013 from 38 men and 32
      women; most of the isolates (48 out of 70, 68.5%) were obtained from post-nasal
      drips of children. The antimicrobial susceptibility of M. catarrhalis isolates
      was determined with an Etest, and low-level fluoroquinolone-resistant isolates
      were subtyped by PFGE. Mutations in the gyrA and parC genes were determined by
      PCR and sequencing. PCR products of the gyrA and parC genes from the low-level
      fluoroquinolone-resistant isolates were transformed into a fluoroquinolone
      susceptible strain. Among the 70 isolates, five (7.1%) exhibited elevated
      fluoroquinolone MICs (levofloxacin, 1.0 mg l(-1); ciprofloxacin, 0.5 mg l(-1))
      and different PFGE patterns. The patients from whom these five isolates were
      isolated had not undergone treatment with fluoroquinolones for the past 6 months.
      Each of the five low-level fluoroquinolone-resistant isolates had a gyrA gene
      mutation resulting in a Thr-to-Ile substitution at aa 80 (T80I) in the GyrA
      protein, while no changes were detected in the parC gene. A transformant carrying
      the gyrA gene containing the T80I substitution, which corresponded to Ser83 in
      Escherichia coli, displayed an elevated fluoroquinolone MIC and contained the
      T80I alteration in GyrA. Thus, our findings reveal that the low-level resistance
      to fluoroquinolones in M. catarrhalis is due to an amino acid substitution of
      Thr80 to Ile in GyrA. This is the first evidence of low-level fluoroquinolone
      resistance in M. catarrhalis.

PMID- 24850883
TI  - Evaluation of a fourth-generation avidity assay for recent HIV infections among
      men who have sex with men in Amsterdam.

PMID- 24850884
TI  - The SBP2 protein central to selenoprotein synthesis contacts the human ribosome
      at expansion segment 7L of the 28S rRNA.
AB  - SBP2 is a pivotal protein component in selenoprotein synthesis. It binds the
      SECIS stem-loop in the 3' UTR of selenoprotein mRNA and interacts with both the
      specialized translation elongation factor and the ribosome at the 60S subunit. In
      this work, our goal was to identify the binding partners of SBP2 on the ribosome.
      Cross-linking experiments with bifunctional reagents demonstrated that the SBP2
      binding site on the human ribosome is mainly formed by the 28S rRNA. Direct
      hydroxyl radical probing of the entire 28S rRNA revealed that SBP2 bound to 80S
      ribosomes or 60S subunits protects helix ES7L-E in expansion segment 7 of the 28S
      rRNA. Diepoxybutane cross-linking confirmed the interaction of SBP2 with helix
      ES7L-E. Additionally, binding of SBP2 to the ribosome led to increased reactivity
      toward chemical probes of a few bases in ES7L-E and in the universally conserved
      helix H89, indicative of conformational changes in the 28S rRNA in response to
      SBP2 binding. This study revealed for the first time that SBP2 makes direct
      contacts with a discrete region of the human 28S rRNA. 

PMID- 24850886
TI  - The effect of sample storage on the performance and reproducibility of the
      galactomannan EIA test.
AB  - Galactomannan enzyme immune assay (GM EIA) is a nonculture test for detecting
      invasive aspergillosis (IA) forming a key part of diagnosis and management.
      Recent reports have questioned the reproducibility of indices after sample
      storage. To investigate this, 198 serum samples (72 from cases and 126 from
      controls) and 61 plasma samples (24 from cases and 37 from controls), initially
      tested between 2010 and 2013, were retested to determine any change in index.
      Data were also collected on circulatory protein levels for false-positive serum
      samples. Serum indices significantly declined on retesting (median: initial,
      0.50, retest, 0.23; P < 0.0001). This was shown to be diagnosis dependent as the
      decline was apparent on retesting of control samples (median: initial 0.50,
      retest 0.12; P < 0.0001), but was not evident with case samples (median: initial,
      0.80, retest, 0.80; P = 0.724). Plasma samples showed little change on reanalysis
      after long-term storage at 4 degrees C. Retesting after freezing showed a
      decrease in index values for controls (median: initial 0.40, retest 0.26; P =
      0.0505), but no significant change in cases. Circulatory proteins showed a
      correlation between serum albumin concentration and difference in index value on
      retesting. Overall, this study suggests that a lack of reproducibility in GM EIA
      positivity is only significant when disease is absent. Retesting after freezing
      helps to differentiate false-positive GM EIA results and, with consecutive
      positivity, could help to improve accuracy in predicting disease status. The
      freezing of samples prior to testing could potentially reduce false-positivity
      rates and the need to retest.

PMID- 24850885
TI  - The RIDL hypothesis: transposable elements as functional domains of long
      noncoding RNAs.
AB  - Our genome contains tens of thousands of long noncoding RNAs (lncRNAs), many of
      which are likely to have genetic regulatory functions. It has been proposed that
      lncRNA are organized into combinations of discrete functional domains, but the
      nature of these and their identification remain elusive. One class of sequence
      elements that is enriched in lncRNA is represented by transposable elements
      (TEs), repetitive mobile genetic sequences that have contributed widely to genome
      evolution through a process termed exaptation. Here, we link these two concepts
      by proposing that exonic TEs act as RNA domains that are essential for lncRNA
      function. We term such elements Repeat Insertion Domains of LncRNAs (RIDLs). A
      growing number of RIDLs have been experimentally defined, where TE-derived
      fragments of lncRNA act as RNA-, DNA-, and protein-binding domains. We propose
      that these reflect a more general phenomenon of exaptation during lncRNA
      evolution, where inserted TE sequences are repurposed as recognition sites for
      both protein and nucleic acids. We discuss a series of genomic screens that may
      be used in the future to systematically discover RIDLs. The RIDL hypothesis has
      the potential to explain how functional evolution can keep pace with the rapid
      gene evolution observed in lncRNA. More practically, TE maps may in the future be
      used to predict lncRNA function. 

PMID- 24850887
TI  - The family-specific K-loop influences the microtubule on-rate but not the
      superprocessivity of kinesin-3 motors.
AB  - The kinesin-3 family (KIF) is one of the largest among the kinesin superfamily
      and an important driver of a variety of cellular transport events. Whereas all
      kinesins contain the highly conserved kinesin motor domain, different families
      have evolved unique motor features that enable different mechanical and
      functional outputs. A defining feature of kinesin-3 motors is the presence of a
      positively charged insert, the K-loop, in loop 12 of their motor domains.
      However, the mechanical and functional output of the K-loop with respect to
      processive motility of dimeric kinesin-3 motors is unknown. We find that,
      surprisingly, the K-loop plays no role in generating the superprocessive motion
      of dimeric kinesin-3 motors (KIF1, KIF13, and KIF16). Instead, we find that the K
      loop provides kinesin-3 motors with a high microtubule affinity in the motor's
      ADP-bound state, a state that for other kinesins binds only weakly to the
      microtubule surface. A high microtubule affinity results in a high landing rate
      of processive kinesin-3 motors on the microtubule surface. We propose that the
      family-specific K-loop contributes to efficient kinesin-3 cargo transport by
      enhancing the initial interaction of dimeric motors with the microtubule track. 

PMID- 24850888
TI  - A comprehensive protein-protein interactome for yeast PAS kinase 1 reveals direct
      inhibition of respiration through the phosphorylation of Cbf1.
AB  - Per-Arnt-Sim (PAS) kinase is a sensory protein kinase required for glucose
      homeostasis in yeast, mice, and humans, yet little is known about the molecular
      mechanisms of its function. Using both yeast two-hybrid and copurification
      approaches, we identified the protein-protein interactome for yeast PAS kinase 1
      (Psk1), revealing 93 novel putative protein binding partners. Several of the Psk1
      binding partners expand the role of PAS kinase in glucose homeostasis, including
      new pathways involved in mitochondrial metabolism. In addition, the interactome
      suggests novel roles for PAS kinase in cell growth (gene/protein expression,
      replication/cell division, and protein modification and degradation), vacuole
      function, and stress tolerance. In vitro kinase studies using a subset of 25 of
      these binding partners identified Mot3, Zds1, Utr1, and Cbf1 as substrates.
      Further evidence is provided for the in vivo phosphorylation of Cbf1 at T211/T212
      and for the subsequent inhibition of respiration. This respiratory role of PAS
      kinase is consistent with the reported hypermetabolism of PAS kinase-deficient
      mice, identifying a possible molecular mechanism and solidifying the evolutionary
      importance of PAS kinase in the regulation of glucose homeostasis. 

PMID- 24850889
TI  - Transcription regulation during stable elongation by a reversible halt of RNA
      polymerase II.
AB  - Regulation of RNA polymerase II (RNAPII) during transcription is essential for
      controlling gene expression. Here we report that the transcriptional activity of
      RNAPII at the Balbiani ring 2.1 gene could be halted during stable elongation in
      salivary gland cells of Chironomus tentans larvae for extended time periods in a
      regulated manner. The transcription halt was triggered by heat shock and affected
      all RNAPII independently of their position in the gene. During the halt,
      incomplete transcripts and RNAPII remained at the transcription site, the
      phosphorylation state of RNAPII was unaltered, and the transcription bubbles
      remained open. The transcription of halted transcripts was resumed upon relief of
      the heat shock. The observed mechanism allows cells to interrupt transcription
      for extended time periods and rapidly reactivate it without the need to
      reinitiate transcription of the complete gene. Our results suggest a so-far
      unknown level of transcriptional control in eukaryotic cells. 

PMID- 24850890
TI  - The 14-3-3 protein Bmh1 functions in the spindle position checkpoint by breaking
      Bfa1 asymmetry at yeast centrosomes.
AB  - In addition to their well-known role in microtubule organization, centrosomes
      function as signaling platforms and regulate cell cycle events. An important
      example of such a function is the spindle position checkpoint (SPOC) of budding
      yeast. SPOC is a surveillance mechanism that ensures alignment of the mitotic
      spindle along the cell polarity axis. Upon spindle misalignment, phosphorylation
      of the SPOC component Bfa1 by Kin4 kinase engages the SPOC by changing the
      centrosome localization of Bfa1 from asymmetric (one centrosome) to symmetric
      (both centrosomes). Here we show that, unexpectedly, Kin4 alone is unable to
      break Bfa1 asymmetry at yeast centrosomes. Instead, phosphorylation of Bfa1 by
      Kin4 creates a docking site on Bfa1 for the 14-3-3 family protein Bmh1, which in
      turn weakens Bfa1-centrosome association and promotes symmetric Bfa1
      localization. Consistently, BMH1-null cells are SPOC deficient. Our work thus
      identifies Bmh1 as a new SPOC component and refines the molecular mechanism that
      breaks Bfa1 centrosome asymmetry upon SPOC activation. 

PMID- 24850891
TI  - Variation in harbour porpoise activity in response to seismic survey noise.
AB  - Animals exposed to anthropogenic disturbance make trade-offs between perceived
      risk and the cost of leaving disturbed areas. Impact assessments tend to focus on
      overt behavioural responses leading to displacement, but trade-offs may also
      impact individual energy budgets through reduced foraging performance. Previous
      studies found no evidence for broad-scale displacement of harbour porpoises
      exposed to impulse noise from a 10 day two-dimensional seismic survey. Here, we
      used an array of passive acoustic loggers coupled with calibrated noise
      measurements to test whether the seismic survey influenced the activity patterns
      of porpoises remaining in the area. We showed that the probability of recording a
      buzz declined by 15% in the ensonified area and was positively related to
      distance from the source vessel. We also estimated received levels at the
      hydrophones and characterized the noise response curve. Our results demonstrate
      how environmental impact assessments can be developed to assess more subtle
      effects of noise disturbance on activity patterns and foraging efficiency. 

PMID- 24850892
TI  - Marmoset monkeys evaluate third-party reciprocity.
AB  - Many non-human primates have been observed to reciprocate and to understand
      reciprocity in one-to-one social exchanges. A recent study demonstrated that
      capuchin monkeys are sensitive to both third-party reciprocity and violation of
      reciprocity; however, whether this sensitivity is a function of general
      intelligence, evidenced by their larger brain size relative to other primates,
      remains unclear. We hypothesized that highly pro-social primates, even with a
      relatively smaller brain, would be sensitive to others' reciprocity. Here, we
      show that common marmosets discriminated between human actors who reciprocated in
      social exchanges with others and those who did not. Monkeys accepted rewards less
      frequently from non-reciprocators than they did from reciprocators when the non
      reciprocators had retained all food items, but they accepted rewards from both
      actors equally when they had observed reciprocal exchange between the actors.
      These results suggest that mechanisms to detect unfair reciprocity in third-party
      social exchanges do not require domain-general higher cognitive ability based on
      proportionally larger brains, but rather emerge from the cooperative and pro
      social tendencies of species, and thereby suggest this ability evolved in
      multiple primate lineages. 

PMID- 24850893
TI  - Flow cytometric sexing of spider sperm reveals an equal sperm production ratio in
      a female-biased species.
AB  - Producing equal amounts of male and female offspring has long been considered an
      evolutionarily stable strategy. Nevertheless, exceptions to this general rule
      (i.e. male and female biases) are documented in many taxa, making sex allocation
      an important domain in current evolutionary biology research. Pinpointing the
      underlying mechanism of sex ratio bias is challenging owing to the multitude of
      potential sex ratio-biasing factors. In the dwarf spider, Oedothorax gibbosus,
      infection with the bacterial endosymbiont Wolbachia results in a female bias.
      However, pedigree analysis reveals that other factors influence sex ratio
      variation. In this paper, we investigate whether this additional variation can be
      explained by the unequal production of male- and female-determining sperm cells
      during sperm production. Using flow cytometry, we show that males produce equal
      amounts of male- and female-determining sperm cells; thus bias in sperm
      production does not contribute to the sex ratio bias observed in this species.
      This demonstrates that other factors such as parental genes suppressing
      endosymbiont effects and cryptic female choice might play a role in sex
      allocation in this species. 

PMID- 24850894
TI  - Fitness consequences of spousal relatedness in 46 small-scale societies.
AB  - Social norms that regulate reproductive and marital decisions generate impressive
      cross-cultural variation in the prevalence of kin marriages. In some societies,
      marriages among kin are the norm and this inbreeding creates intensive kinship
      networks concentrated within communities. In others, especially forager
      societies, most marriages are between more genealogically and geographically
      distant individuals, which generates a larger number of kin and affines of lesser
      relatedness in more extensive kinship networks spread out over multiple
      communities. Here, we investigate the fitness consequence of kin marriages across
      a sample of 46 small-scale societies (12,439 marriages). Results show that some
      non-forager societies (including horticulturalists, agriculturalists and
      pastoralists), but not foragers, have intensive kinship societies where fitness
      outcomes (measured as the number of surviving children in genealogies) peak at
      commonly high levels of spousal relatedness. By contrast, the extensive kinship
      systems of foragers have worse fitness outcomes at high levels of spousal
      relatedness. Overall, societies with greater levels of inbreeding showed a more
      positive relationship between fitness and spousal relatedness.

PMID- 24850895
TI  - Maternally derived chemical defences are an effective deterrent against some
      predators of poison frog tadpoles (Oophaga pumilio).
AB  - Parents defend their young in many ways, including provisioning chemical
      defences. Recent work in a poison frog system offers the first example of an
      animal that provisions its young with alkaloids after hatching or birth rather
      than before. But it is not yet known whether maternally derived alkaloids are an
      effective defence against offspring predators. We identified the predators of
      Oophaga pumilio tadpoles and conducted laboratory and field choice tests to
      determine whether predators are deterred by alkaloids in tadpoles. We found that
      snakes, spiders and beetle larvae are common predators of O. pumilio tadpoles.
      Snakes were not deterred by alkaloids in tadpoles. However, spiders were less
      likely to consume mother-fed O. pumilio tadpoles than either alkaloid-free
      tadpoles of the red-eyed treefrog, Agalychnis callidryas, or alkaloid-free O.
      pumilio tadpoles that had been hand-fed with A. callidryas eggs. Thus, maternally
      derived alkaloids reduce the risk of predation for tadpoles, but only against
      some predators. 

PMID- 24850897
TI  - Local competition sparks concerns for fairness in the ultimatum game.
AB  - Humans reject uneven divisions of resources, even at personal cost. This is
      observed in countless experiments using the ultimatum game, where a proposer
      offers to divide a resource with a responder who either accepts the division or
      rejects it (whereupon both earn zero). Researchers debate why humans evolved a
      psychology that is so averse to inequity within partnerships. We suggest that the
      scale of competition is crucial: under local competition with few competitors,
      individuals reject low offers, because they cannot afford to be disadvantaged
      relative to competitors. If one competes against the broader population (i.e.
      global competition), then it pays to accept low offers to increase one's absolute
      pay-off. We support this intuition with an illustrative game-theoretical model.
      We also conducted ultimatum games where participants received prizes based on pay
      offs relative to immediate partners (local competition) versus a larger group
      (global competition). Participants demanded higher offers under local
      competition, suggesting that local competition increases people's demands for
      fairness and aversion to inequality. 

PMID- 24850896
TI  - Human face processing is tuned to sexual age preferences.
AB  - Human faces can motivate nurturing behaviour or sexual behaviour when adults see
      a child or an adult face, respectively. This suggests that face processing is
      tuned to detecting age cues of sexual maturity to stimulate the appropriate
      reproductive behaviour: either caretaking or mating. In paedophilia, sexual
      attraction is directed to sexually immature children. Therefore, we hypothesized
      that brain networks that normally are tuned to mature faces of the preferred
      gender show an abnormal tuning to sexual immature faces in paedophilia. Here, we
      use functional magnetic resonance imaging (fMRI) to test directly for the
      existence of a network which is tuned to face cues of sexual maturity. During
      fMRI, participants sexually attracted to either adults or children were exposed
      to various face images. In individuals attracted to adults, adult faces activated
      several brain regions significantly more than child faces. These brain regions
      comprised areas known to be implicated in face processing, and sexual processing,
      including occipital areas, the ventrolateral prefrontal cortex and,
      subcortically, the putamen and nucleus caudatus. The same regions were activated
      in paedophiles, but with a reversed preferential response pattern. 

PMID- 24850898
TI  - Plain faces are more expressive: comparative study of facial colour, mobility and
      musculature in primates.
AB  - Facial colour patterns and facial expressions are among the most important
      phenotypic traits that primates use during social interactions. While colour
      patterns provide information about the sender's identity, expressions can
      communicate its behavioural intentions. Extrinsic factors, including social group
      size, have shaped the evolution of facial coloration and mobility, but intrinsic
      relationships and trade-offs likely operate in their evolution as well. We
      hypothesize that complex facial colour patterning could reduce how salient facial
      expressions appear to a receiver, and thus species with highly expressive faces
      would have evolved uniformly coloured faces. We test this hypothesis through a
      phylogenetic comparative study, and explore the underlying morphological factors
      of facial mobility. Supporting our hypothesis, we find that species with highly
      expressive faces have plain facial colour patterns. The number of facial muscles
      does not predict facial mobility; instead, species that are larger and have a
      larger facial nucleus have more expressive faces. This highlights a potential
      trade-off between facial mobility and colour patterning in primates and reveals
      complex relationships between facial features during primate evolution. 

PMID- 24850899
TI  - Natural variation in abiotic stress responsive gene expression and local
      adaptation to climate in Arabidopsis thaliana.
AB  - Gene expression varies widely in natural populations, yet the proximate and
      ultimate causes of this variation are poorly known. Understanding how variation
      in gene expression affects abiotic stress tolerance, fitness, and adaptation is
      central to the field of evolutionary genetics. We tested the hypothesis that
      genes with natural genetic variation in their expression responses to abiotic
      stress are likely to be involved in local adaptation to climate in Arabidopsis
      thaliana. Specifically, we compared genes with consistent expression responses to
      environmental stress (expression stress responsive, "eSR") to genes with
      genetically variable responses to abiotic stress (expression genotype-by
      environment interaction, "eGEI"). We found that on average genes that exhibited
      eGEI in response to drought or cold had greater polymorphism in promoter regions
      and stronger associations with climate than those of eSR genes or genomic
      controls. We also found that transcription factor binding sites known to respond
      to environmental stressors, especially abscisic acid responsive elements, showed
      significantly higher polymorphism in drought eGEI genes in comparison to eSR
      genes. By contrast, eSR genes tended to exhibit relatively greater pairwise
      haplotype sharing, lower promoter diversity, and fewer nonsynonymous
      polymorphisms, suggesting purifying selection or selective sweeps. Our results
      indicate that cis-regulatory evolution and genetic variation in stress responsive
      gene expression may be important mechanisms of local adaptation to climatic
      selective gradients. 

PMID- 24850900
TI  - MIF antagonist (CPSI-1306) protects against UVB-induced squamous cell carcinoma.
AB  - Macrophage migration inhibitory factor (MIF) is a homotrimeric proinflammatory
      cytokine implicated in chronic inflammatory diseases and malignancies, including
      cutaneous squamous cell carcinomas (SCC). To determine whether MIF inhibition
      could reduce UVB light-induced inflammation and squamous carcinogenesis, a small
      molecule MIF inhibitor (CPSI-1306) was utilized that disrupts homotrimerization.
      To examine the effect of CPSI-1306 on acute UVB-induced skin changes, Skh-1
      hairless mice were systemically treated with CPSI-1306 for 5 days before UVB
      exposure. In addition to decreasing skin thickness and myeloperoxidase (MPO)
      activity, CPSI-1306 pretreatment increased keratinocyte apoptosis and p53
      expression, decreased proliferation and phosphohistone variant H2AX (gamma-H2AX),
      and enhanced repair of cyclobutane pyrimidine dimers. To examine the effect of
      CPSI-1306 on squamous carcinogenesis, mice were exposed to UVB for 10 weeks,
      followed by CPSI-1306 treatment for 8 weeks. CPSI-1306 dramatically decreased the
      density of UVB-associated p53 foci in non-tumor-bearing skin while simultaneously
      decreasing the epidermal Ki67 proliferation index. In addition to slowing the
      rate of tumor development, CPSI-1306 decreased the average tumor burden per
      mouse. Although CPSI-1306-treated mice developed only papillomas, nearly a third
      of papillomas in vehicle-treated mice progressed to microinvasive SCC. Thus, MIF
      inhibition is a promising strategy for prevention of the deleterious cutaneous
      effects of acute and chronic UVB exposure. IMPLICATIONS: Macrophage migration
      inhibitory factor is a viable target for the prevention of UVB-induced cutaneous
      SSCs.

PMID- 24850901
TI  - Hypoxia regulates alternative splicing of HIF and non-HIF target genes.
AB  - Hypoxia is a common characteristic of many solid tumors. The hypoxic
      microenvironment stabilizes hypoxia-inducible transcription factor 1alpha
      (HIF1alpha) and 2alpha (HIF2alpha/EPAS1) to activate gene transcription, which
      promotes tumor cell survival. The majority of human genes are alternatively
      spliced, producing RNA isoforms that code for functionally distinct proteins.
      Thus, an effective hypoxia response requires increased HIF target gene expression
      as well as proper RNA splicing of these HIF-dependent transcripts. However, it is
      unclear if and how hypoxia regulates RNA splicing of HIF targets. This study
      determined the effects of hypoxia on alternative splicing (AS) of HIF and non-HIF
      target genes in hepatocellular carcinoma cells and characterized the role of HIF
      in regulating AS of HIF-induced genes. The results indicate that hypoxia
      generally promotes exon inclusion for hypoxia-induced, but reduces exon inclusion
      for hypoxia-reduced genes. Mechanistically, HIF activity, but not hypoxia per se
      is found to be necessary and sufficient to increase exon inclusion of several HIF
      targets, including pyruvate dehydrogenase kinase 1 (PDK1). PDK1 splicing
      reporters confirm that transcriptional activation by HIF is sufficient to
      increase exon inclusion of PDK1 splicing reporter. In contrast, transcriptional
      activation of a PDK1 minigene by other transcription factors in the absence of
      endogenous HIF target gene activation fails to alter PDK1 RNA splicing.
      IMPLICATIONS: This study demonstrates a novel function of HIF in regulating RNA
      splicing of HIF target genes.

PMID- 24850902
TI  - Tumor cell-derived MMP3 orchestrates Rac1b and tissue alterations that promote
      pancreatic adenocarcinoma.
AB  - Pancreatic ductal adenocarcinoma (PDA) arises at the convergence of genetic
      alterations in KRAS with a fostering microenvironment shaped by immune cell
      influx and fibrotic changes; identification of the earliest tumorigenic molecular
      mediators evokes the proverbial chicken and egg problem. Matrix
      metalloproteinases (MMP) are key drivers of tumor progression that originate
      primarily from stromal cells activated by the developing tumor. Here, MMP3, known
      to be expressed in PDA, was found to be associated with expression of Rac1b, a
      tumorigenic splice isoform of Rac1, in all stages of pancreatic cancer. Using a
      large cohort of human PDA tissue biopsies specimens, both MMP3 and Rac1b are
      expressed in PDA cells, that the expression levels of the two markers are highly
      correlated, and that the subcellular distribution of Rac1b in PDA is
      significantly associated with patient outcome. Using transgenic mouse models,
      coexpression of MMP3 with activated KRAS in pancreatic acinar cells stimulates
      metaplasia and immune cell infiltration, priming the stromal microenvironment for
      early tumor development. Finally, exposure of cultured pancreatic cancer cells to
      recombinant MMP3 stimulates expression of Rac1b, increases cellular invasiveness,
      and activation of tumorigenic transcriptional profiles. IMPLICATIONS: MMP3 acts
      as a coconspirator of oncogenic KRAS in pancreatic cancer tumorigenesis and
      progression, both through Rac1b-mediated phenotypic control of pancreatic cancer
      cells themselves, and by giving rise to the tumorigenic microenvironment; these
      findings also point to inhibition of this pathway as a potential therapeutic
      strategy for pancreatic cancer.

PMID- 24850903
TI  - Spaces of the possible: universal Darwinism and the wall between technological
      and biological innovation.
AB  - Innovations in biological evolution and in technology have many common features.
      Some of them involve similar processes, such as trial and error and horizontal
      information transfer. Others describe analogous outcomes such as multiple
      independent origins of similar innovations. Yet others display similar temporal
      patterns such as episodic bursts of change separated by periods of stasis. We
      review nine such commonalities, and propose that the mathematical concept of a
      space of innovations, discoveries or designs can help explain them. This concept
      can also help demolish a persistent conceptual wall between technological and
      biological innovation. 

PMID- 24850904
TI  - A stochastic model for early placental development.
AB  - In the human, placental structure is closely related to placental function and
      consequent pregnancy outcome. Studies have noted abnormal placental shape in
      small-for-gestational-age infants which extends to increased lifetime risk of
      cardiovascular disease. The origins and determinants of placental shape are
      incompletely understood and are difficult to study in vivo. In this paper, we
      model the early development of the human placenta, based on the hypothesis that
      this is driven by a chemoattractant effect emanating from proximal spiral
      arteries in the decidua. We derive and explore a two-dimensional stochastic
      model, and investigate the effects of loss of spiral arteries in regions near to
      the cord insertion on the shape of the placenta. This model demonstrates that
      disruption of spiral arteries can exert profound effects on placental shape,
      particularly if this is close to the cord insertion. Thus, placental shape
      reflects the underlying maternal vascular bed. Abnormal placental shape may
      reflect an abnormal uterine environment, predisposing to pregnancy complications.
      Through statistical analysis of model placentas, we are able to characterize the
      probability that a given placenta grew in a disrupted environment, and even able
      to distinguish between different disruptions. 

PMID- 24850905
TI  - Reinitiation enhances reliable transcriptional responses in eukaryotes.
AB  - Gene transcription is a noisy process carried out by the transcription machinery
      recruited to the promoter. Noise reduction is a fundamental requirement for
      reliable transcriptional responses which in turn are crucial for signal
      transduction. Compared with the relatively simple transcription initiation in
      prokaryotes, eukaryotic transcription is more complex partially owing to its
      additional reinitiation mechanism. By theoretical analysis, we showed that
      reinitiation reduces noise in eukaryotic transcription independent of the
      transcription level. Besides, a higher reinitiation rate enables a stable
      scaffold complex an advantage in noise reduction. Finally, we showed that the
      coupling between scaffold formation and transcription can further reduce
      transcription noise independent of the transcription level. Furthermore, compared
      with the reinitiation mechanism, the noise reduction effect of the coupling can
      be of more significance in the case that the transcription level is low and the
      intrinsic noise dominates. Our results uncover a mechanistic route which
      eukaryotes may use to facilitate a more reliable response in the noisy
      transcription process. 

PMID- 24850906
TI  - How much information can be obtained from tracking the position of the leading
      edge in a scratch assay?
AB  - Moving cell fronts are an essential feature of wound healing, development and
      disease. The rate at which a cell front moves is driven, in part, by the cell
      motility, quantified in terms of the cell diffusivity D, and the cell
      proliferation rate lambda. Scratch assays are a commonly reported procedure used
      to investigate the motion of cell fronts where an initial cell monolayer is
      scratched, and the motion of the front is monitored over a short period of time,
      often less than 24 h. The simplest way of quantifying a scratch assay is to
      monitor the progression of the leading edge. Use of leading edge data is very
      convenient because, unlike other methods, it is non-destructive and does not
      require labelling, tracking or counting individual cells among the population. In
      this work, we study short-time leading edge data in a scratch assay using a
      discrete mathematical model and automated image analysis with the aim of
      investigating whether such data allow us to reliably identify D and lambda. Using
      a naive calibration approach where we simply scan the relevant region of the (D,
      lambda) parameter space, we show that there are many choices of D and lambda for
      which our model produces indistinguishable short-time leading edge data.
      Therefore, without due care, it is impossible to estimate D and lambda from this
      kind of data. To address this, we present a modified approach accounting for the
      fact that cell motility occurs over a much shorter time scale than proliferation.
      Using this information, we divide the duration of the experiment into two
      periods, and we estimate D using data from the first period, whereas we estimate
      lambda using data from the second period. We confirm the accuracy of our approach
      using in silico data and a new set of in vitro data, which shows that our method
      recovers estimates of D and lambda that are consistent with previously reported
      values except that that our approach is fast, inexpensive, non-destructive and
      avoids the need for cell labelling and cell counting. 

PMID- 24850907
TI  - Synergy between shear-induced migration and secondary flows on red blood cells
      transport in arteries: considerations on oxygen transport.
AB  - Shear-induced migration of red blood cells (RBCs) is a well-known phenomenon
      characterizing blood flow in the small vessels (micrometre to millimetre size) of
      the cardiovascular system. In large vessels, like the abdominal aorta and the
      carotid artery (millimetre to centimetre size), the extent of this migration and
      its interaction with secondary flows has not been fully elucidated. RBC migration
      exerts its influence primarily on platelet concentration, oxygen transport and
      oxygen availability at the luminal surface, which could influence vessel wall
      disease processes in and adjacent to the intima. Phillips' shear-induced particle
      migration model, coupled to the Quemada viscosity model, was employed to simulate
      the macroscopic behaviour of RBCs in four patient-specific geometries: a normal
      abdominal aorta, an abdominal aortic aneurysm (AAA), a normal carotid bifurcation
      and a stenotic carotid bifurcation. Simulations show a migration of RBCs from the
      near-wall region with a lowering of wall haematocrit (volume fraction of RBCs) on
      the posterior side of the normal aorta and on the lateral-external side of the
      iliac arteries. A marked migration is observed on the outer wall of the carotid
      sinus, along the common carotid artery and in the carotid stenosis. No
      significant migration is observed in the AAA. The spatial and temporal patterns
      of wall haematocrit are correlated with the near-wall shear layer and with the
      secondary flows induced by the vessel curvature. In particular, secondary flows
      accentuate the initial lowering in RBC near-wall concentration by convecting RBCs
      from the inner curvature side to the outer curvature side. The results reinforce
      data in literature showing a decrease in oxygen partial pressure on the inner
      curvature wall of the carotid sinus induced by the presence of secondary flows.
      The lowering of wall haematocrit is postulated to induce a decrease in oxygen
      availability at the luminal surface through a diminished concentration of
      oxyhaemoglobin, hence contributing, with the reported lowered oxygen partial
      pressure, to local hypoxia. 

PMID- 24850908
TI  - Notch-dependent RBPJkappa inhibits proliferation of human cytotrophoblasts and
      their differentiation into extravillous trophoblasts.
AB  - Abnormal development of invasive trophoblasts has been implicated in the
      pathogenesis of human pregnancy diseases such as pre-eclampsia. However, critical
      signalling pathways controlling formation and differentiation of these cells have
      been poorly elucidated. Here, we provide evidence that the canonical Notch
      pathway, operating through Notch-dependent activation of its key regulatory
      transcription factor RBPJkappa, controls proliferation and differentiation in
      villous explant cultures and primary trophoblasts of early pregnancy.
      Immunofluorescence of first trimester placental tissue revealed expression of
      RBPJkappa and its co-activators, the MAML proteins, in nuclei of proliferative
      cell column trophoblasts (CCT) and differentiated, extravillous trophoblasts
      (EVTs). However, RBPJkappa expression, transcript levels of the Notch target gene
      HES1 and activity of a Notch/RBPJkappa-dependent luciferase reporter decreased
      during in vitro differentiation of primary cytotrophoblasts on fibronectin.
      Silencing of RBPJkappa using silencing RNAs (siRNAs) increased proliferation of
      CCTs in floating villous explant cultures analysed by outgrowth and BrdU
      labelling. Similarly, down-regulation of the transcription factor enhanced BrdU
      incorporation in isolated primary cultures. However, motility of these cells was
      not affected. In addition, gene silencing of RBPJkappa increased cyclin D1
      expression in the two trophoblast model systems as well as markers of the
      differentiated, EVT, i.e. integrin alpha1, ADAM12 and T-cell factor 4. In
      summary, the data suggest that Notch-dependent RBPJkappa activity could be
      required for balanced rates of trophoblast proliferation and differentiation in
      human placental anchoring villi preventing exaggerated trophoblast overgrowth as
      well as premature formation of EVTs. 

PMID- 24850909
TI  - Globular adiponectin inhibits ethanol-induced reactive oxygen species production
      through modulation of NADPH oxidase in macrophages: involvement of liver kinase
      B1/AMP-activated protein kinase pathway.
AB  - Adiponectin, an adipokine predominantly secreted from adipocytes, has been shown
      to play protective roles against chronic alcohol consumption. Although excessive
      reactive oxygen species (ROS) production in macrophages is considered one of the
      critical events for ethanol-induced damage in various target tissues, the effect
      of adiponectin on ethanol-induced ROS production is not clearly understood. In
      the present study, we investigated the effect of globular adiponectin (gAcrp) on
      ethanol-induced ROS production and the potential mechanisms underlying these
      effects of gAcrp in macrophages. Here we demonstrated that gAcrp prevented
      ethanol-induced ROS production in both RAW 264.7 macrophages and primary murine
      peritoneal macrophages. Globular adiponectin also inhibited ethanol-induced
      activation of NADPH oxidase. In addition, gAcrp suppressed ethanol-induced
      increase in the expression of NADPH oxidase subunits, including Nox2 and
      p22(phox), via modulation of nuclear factor-kappaB pathway. Furthermore,
      pretreatment with compound C, a selective inhibitor of AMPK, or knockdown of AMPK
      by small interfering RNA restored suppression of ethanol-induced ROS production
      and Nox2 expression by gAcrp. Finally, we found that gAcrp treatment induced
      phosphorylation of liver kinase B1 (LKB1), an upstream signaling molecule
      mediating AMPK activation. Knockdown of LKB1 restored gAcrp-suppressed Nox2
      expression, suggesting that LKB1/AMPK pathway plays a critical role in the
      suppression of ethanol-induced ROS production and activation of NADPH oxidase by
      gAcrp. Taken together, these results demonstrate that globular adiponectin
      prevents ethanol-induced ROS production, at least in part, via modulation of
      NADPH oxidase in macrophages. Further, LKB1/AMPK axis plays an important role in
      the suppression of ethanol-induced NADPH oxidase activation by gAcrp in
      macrophages. 

PMID- 24850910
TI  - Angiotensin II and canonical transient receptor potential-6 activation stimulate
      release of a signal transducer and activator of transcription 3-activating factor
      from mouse podocytes.
AB  - Previous studies have shown that the transcription factor signal transducer and
      activator of transcription-3 (STAT3) in podocytes plays an important role in
      progression of HIV nephropathy and in collapsing forms of glomerulonephritis.
      Here, we have observed that application of 100 nM angiotensin II (Ang II) to
      cultured podocytes for 6-24 hours causes a marked increase in the phosphorylation
      of STAT3 on tyrosine Y705 but has no effect on phosphorylation at serine S727. By
      contrast, Ang II treatment of short periods (20-60 minutes) caused a small but
      consistent suppression of tyrosine phosphylation of STAT3. A similar biphasic
      effect was seen after treatment with the diacylglycerol analog 1-oleoyl-2-acetyl
      sn-glycerol (OAG), an agent that causes activation of Ca(2+)-permeable canonical
      transient receptor potential-6 (TRPC6) channels in podocytes. The stimulatory
      effects of Ang II on STAT3 phosphorylation were abolished by small-interfering
      RNA knockdown of TRPC6 and also by inhibitors of the Ca(2+)-dependent downstream
      enzymes calcineurin and Ca(2+)-calmodulin-dependent protein kinase II. The
      stimulatory effects of Ang II appear to be mediated by secretion and accumulation
      of an unknown factor into the surrounding medium, as they are no longer detected
      when medium is replaced every 2 hours even if Ang II is continuously present. By
      contrast, the inhibitory effect of Ang II on STAT3 phosphorylation persists with
      frequent medium changes. Experiments with neutralizing and inhibitory antibodies
      suggest that the STAT3 stimulatory factor secreted from podocytes is not
      interleukin-6, but also suggest that this factor exerts its actions through a
      receptor system that requires glycoprotein 130. 

PMID- 24850911
TI  - Titin kinase is an inactive pseudokinase scaffold that supports MuRF1 recruitment
      to the sarcomeric M-line.
AB  - Striated muscle tissues undergo adaptive remodelling in response to mechanical
      load. This process involves the myofilament titin and, specifically, its kinase
      domain (TK; titin kinase) that translates mechanical signals into regulatory
      pathways of gene expression in the myofibril. TK mechanosensing appears mediated
      by a C-terminal regulatory tail (CRD) that sterically inhibits its active site.
      Allegedly, stretch-induced unfolding of this tail during muscle function releases
      TK inhibition and leads to its catalytic activation. However, the cellular
      pathway of TK is poorly understood and substrates proposed to date remain
      controversial. TK's best-established substrate is Tcap, a small structural
      protein of the Z-disc believed to link TK to myofibrillogenesis. Here, we show
      that TK is a pseudokinase with undetectable levels of catalysis and, therefore,
      that Tcap is not its substrate. Inactivity is the result of two atypical residues
      in TK's active site, M34 and E147, that do not appear compatible with canonical
      kinase patterns. While not mediating stretch-dependent phospho-transfers, TK
      binds the E3 ubiquitin ligase MuRF1 that promotes sarcomeric ubiquitination in a
      stress-induced manner. Given previous evidence of MuRF2 interaction, we propose
      that the cellular role of TK is to act as a conformationally regulated scaffold
      that functionally couples the ubiquitin ligases MuRF1 and MuRF2, thereby
      coordinating muscle-specific ubiquitination pathways and myofibril trophicity.
      Finally, we suggest that an evolutionary dichotomy of kinases/pseudokinases has
      occurred in TK-like kinases, where invertebrate members are active enzymes but
      vertebrate counterparts perform their signalling function as pseudokinase
      scaffolds. 

PMID- 24850913
TI  - Atomic force microscopy-based microrheology reveals significant differences in
      the viscoelastic response between malign and benign cell lines.
AB  - Mechanical phenotyping of cells by atomic force microscopy (AFM) was proposed as
      a novel tool in cancer cell research as cancer cells undergo massive structural
      changes, comprising remodelling of the cytoskeleton and changes of their adhesive
      properties. In this work, we focused on the mechanical properties of human breast
      cell lines with different metastatic potential by AFM-based microrheology
      experiments. Using this technique, we are not only able to quantify the
      mechanical properties of living cells in the context of malignancy, but we also
      obtain a descriptor, namely the loss tangent, which provides model-independent
      information about the metastatic potential of the cell line. Including also other
      cell lines from different organs shows that the loss tangent (G"/G') increases
      generally with the metastatic potential from MCF-10A representing benign cells to
      highly malignant MDA-MB-231 cells. 

PMID- 24850912
TI  - Reduced ribosomes of the apicoplast and mitochondrion of Plasmodium spp. and
      predicted interactions with antibiotics.
AB  - Apicomplexan protists such as Plasmodium and Toxoplasma contain a mitochondrion
      and a relic plastid (apicoplast) that are sites of protein translation. Although
      there is emerging interest in the partitioning and function of translation
      factors that participate in apicoplast and mitochondrial peptide synthesis, the
      composition of organellar ribosomes remains to be elucidated. We carried out an
      analysis of the complement of core ribosomal protein subunits that are encoded by
      either the parasite organellar or nuclear genomes, accompanied by a survey of
      ribosome assembly factors for the apicoplast and mitochondrion. A cross-species
      comparison with other apicomplexan, algal and diatom species revealed
      compositional differences in apicomplexan organelle ribosomes and identified
      considerable reduction and divergence with ribosomes of bacteria or characterized
      organelle ribosomes from other organisms. We assembled structural models of
      sections of Plasmodium falciparum organellar ribosomes and predicted interactions
      with translation inhibitory antibiotics. Differences in predicted drug-ribosome
      interactions with some of the modelled structures suggested specificity of
      inhibition between the apicoplast and mitochondrion. Our results indicate that
      Plasmodium and Toxoplasma organellar ribosomes have a unique composition,
      resulting from the loss of several large and small subunit proteins accompanied
      by significant sequence and size divergences in parasite orthologues of ribosomal
      proteins. 

PMID- 24850914
TI  - USP15 targets ALK3/BMPR1A for deubiquitylation to enhance bone morphogenetic
      protein signalling.
AB  - Protein kinase ALK3/BMPR1A mediates bone morphogenetic protein (BMP) signalling
      through phosphorylation and activation of SMADs 1/5/8. SMAD6, a transcriptional
      target of BMP, negatively regulates the BMP pathway by recruiting E3 ubiquitin
      ligases and targeting ALK3 for ubiquitin-mediated degradation. Here, we identify
      a deubiquitylating enzyme USP15 as an interactor of SMAD6 and ALK3. We show that
      USP15 enhances BMP-induced phosphorylation of SMAD1 by interacting with and
      deubiquitylating ALK3. RNAi-mediated depletion of USP15 increases ALK3 K48-linked
      polyubiquitylation, and reduces both BMP-induced SMAD1 phosphorylation and
      transcription of BMP target genes. We also show that loss of USP15 expression
      from mouse myoblast cells inhibits BMP-induced osteoblast differentiation.
      Furthermore, USP15 modulates BMP-induced phosphorylation of SMAD1 and
      transcription during Xenopus embryogenesis. 

PMID- 24850915
TI  - Moving in time: Bayesian causal inference explains movement coordination to
      auditory beats.
AB  - Many everyday skilled actions depend on moving in time with signals that are
      embedded in complex auditory streams (e.g. musical performance, dancing or simply
      holding a conversation). Such behaviour is apparently effortless; however, it is
      not known how humans combine auditory signals to support movement production and
      coordination. Here, we test how participants synchronize their movements when
      there are potentially conflicting auditory targets to guide their actions.
      Participants tapped their fingers in time with two simultaneously presented
      metronomes of equal tempo, but differing in phase and temporal regularity.
      Synchronization therefore depended on integrating the two timing cues into a
      single-event estimate or treating the cues as independent and thereby selecting
      one signal over the other. We show that a Bayesian inference process explains the
      situations in which participants choose to integrate or separate signals, and
      predicts motor timing errors. Simulations of this causal inference process
      demonstrate that this model provides a better description of the data than other
      plausible models. Our findings suggest that humans exploit a Bayesian inference
      process to control movement timing in situations where the origin of auditory
      signals needs to be resolved. 

PMID- 24850916
TI  - Analyses of evolutionary dynamics in viruses are hindered by a time-dependent
      bias in rate estimates.
AB  - Time-scales of viral evolution and emergence have been studied widely, but are
      often poorly understood. Molecular analyses of viral evolutionary time-scales
      generally rely on estimates of rates of nucleotide substitution, which vary by
      several orders of magnitude depending on the timeframe of measurement. We
      analysed data from all major groups of viruses and found a strong negative
      relationship between estimates of nucleotide substitution rate and evolutionary
      timescale. Strikingly, this relationship was upheld both within and among diverse
      groups of viruses. A detailed case study of primate lentiviruses revealed that
      the combined effects of sequence saturation and purifying selection can explain
      this time-dependent pattern of rate variation. Therefore, our analyses show that
      studies of evolutionary time-scales in viruses require a reconsideration of
      substitution rates as a dynamic, rather than as a static, feature of molecular
      evolution. Improved modelling of viral evolutionary rates has the potential to
      change our understanding of virus origins. 

PMID- 24850917
TI  - First glimpse into Lower Jurassic deep-sea biodiversity: in situ diversification
      and resilience against extinction.
AB  - Owing to the assumed lack of deep-sea macrofossils older than the Late
      Cretaceous, very little is known about the geological history of deep-sea
      communities, and most inference-based hypotheses argue for repeated
      recolonizations of the deep sea from shelf habitats following major
      palaeoceanographic perturbations. We present a fossil deep-sea assemblage of
      echinoderms, gastropods, brachiopods and ostracods, from the Early Jurassic of
      the Glasenbach Gorge, Austria, which includes the oldest known representatives of
      a number of extant deep-sea groups, and thus implies that in situ
      diversification, in contrast to immigration from shelf habitats, played a much
      greater role in shaping modern deep-sea biodiversity than previously thought. A
      comparison with coeval shelf assemblages reveals that, at least in some of the
      analysed groups, significantly more extant families/superfamilies have endured in
      the deep sea since the Early Jurassic than in the shelf seas, which suggests that
      deep-sea biota are more resilient against extinction than shallow-water ones. In
      addition, a number of extant deep-sea families/superfamilies found in the
      Glasenbach assemblage lack post-Jurassic shelf occurrences, implying that if
      there was a complete extinction of the deep-sea fauna followed by replacement
      from the shelf, it must have happened before the Late Jurassic. 

PMID- 24850918
TI  - The chemical cue tetrabromopyrrole from a biofilm bacterium induces settlement of
      multiple Caribbean corals.
AB  - Microbial biofilms induce larval settlement for some invertebrates, including
      corals; however, the chemical cues involved have rarely been identified. Here, we
      demonstrate the role of microbial biofilms in inducing larval settlement with the
      Caribbean coral Porites astreoides and report the first instance of a chemical
      cue isolated from a marine biofilm bacterium that induces complete settlement
      (attachment and metamorphosis) of Caribbean coral larvae. Larvae settled in
      response to natural biofilms, and the response was eliminated when biofilms were
      treated with antibiotics. A similar settlement response was elicited by
      monospecific biofilms of a single bacterial strain, Pseudoalteromonas sp. PS5,
      isolated from the surface biofilm of a crustose coralline alga. The activity of
      Pseudoalteromonas sp. PS5 was attributed to the production of a single compound,
      tetrabromopyrrole (TBP), which has been shown previously to induce metamorphosis
      without attachment in Pacific acroporid corals. In addition to inducing
      settlement of brooded larvae (P. astreoides), TBP also induced larval settlement
      for two broadcast-spawning species, Orbicella (formerly Montastraea) franksi and
      Acropora palmata, indicating that this compound may have widespread importance
      among Caribbean coral species. 

PMID- 24850920
TI  - Nuclear interactions in a heterokaryon: insight from the model Neurospora
      tetrasperma.
AB  - A heterokaryon is a tissue type composed of cells containing genetically
      different nuclei. Although heterokaryosis is commonly found in nature, an
      understanding of the evolutionary implications of this phenomenon is largely
      lacking. Here, we use the filamentous ascomycete Neurospora tetrasperma to study
      the interplay between nuclei in heterokaryons across vegetative and sexual
      developmental stages. This fungus harbours nuclei of two opposite mating types
      (mat A and mat a) in the same cell and is thereby self-fertile. We used
      pyrosequencing of mat-linked SNPs of three heterokaryons to demonstrate that the
      nuclear ratio is consistently biased for mat A-nuclei during mycelial growth
      (mean mat A/mat a ratio 87%), but evens out during sexual development (ratio
      ranging from 40 to 57%). Furthermore, we investigated the association between
      nuclear ratio and expression of alleles of mat-linked genes and found that
      expression is coregulated to obtain a tissue-specific bias in expression ratio:
      during mycelial extension, we found a strong bias in expression for mat A-linked
      genes, that was independent of nuclear ratio, whereas at the sexual stage we
      found an expression bias for genes of the mat a nuclei. Taken together, our data
      indicate that nuclei cooperate to optimize the fitness of the heterokaryon, via
      both altering their nuclear ratios and coregulation genes expressed in the
      different nuclei. 

PMID- 24850919
TI  - Global diversity and oceanic divergence of humpback whales (Megaptera
      novaeangliae).
AB  - Humpback whales (Megaptera novaeangliae) annually undertake the longest
      migrations between seasonal feeding and breeding grounds of any mammal. Despite
      this dispersal potential, discontinuous seasonal distributions and migratory
      patterns suggest that humpbacks form discrete regional populations within each
      ocean. To better understand the worldwide population history of humpbacks, and
      the interplay of this species with the oceanic environment through geological
      time, we assembled mitochondrial DNA control region sequences representing
      approximately 2700 individuals (465 bp, 219 haplotypes) and eight nuclear
      intronic sequences representing approximately 70 individuals (3700 bp, 140
      alleles) from the North Pacific, North Atlantic and Southern Hemisphere. Bayesian
      divergence time reconstructions date the origin of humpback mtDNA lineages to the
      Pleistocene (880 ka, 95% posterior intervals 550-1320 ka) and estimate radiation
      of current Northern Hemisphere lineages between 50 and 200 ka, indicating
      colonization of the northern oceans prior to the Last Glacial Maximum. Coalescent
      analyses reveal restricted gene flow between ocean basins, with long-term
      migration rates (individual migrants per generation) of less than 3.3 for mtDNA
      and less than 2 for nuclear genomic DNA. Genetic evidence suggests that humpbacks
      in the North Pacific, North Atlantic and Southern Hemisphere are on independent
      evolutionary trajectories, supporting taxonomic revision of M. novaeangliae to
      three subspecies. 

PMID- 24850921
TI  - Protein-poor diet reduces host-specific immune gene expression in Bombus
      terrestris.
AB  - Parasites infect hosts non-randomly as genotypes of hosts vary in susceptibility
      to the same genotypes of parasites, but this specificity may be modulated by
      environmental factors such as nutrition. Nutrition plays an important role for
      any physiological investment. As immune responses are costly, resource limitation
      should negatively affect immunity through trade-offs with other physiological
      requirements. Consequently, nutritional limitation should diminish immune
      capacity in general, but does it also dampen differences among hosts? We
      investigated the effect of short-term pollen deprivation on the immune responses
      of our model host Bombus terrestris when infected with the highly prevalent
      natural parasite Crithidia bombi. Bumblebees deprived of pollen, their protein
      source, show reduced immune responses to infection. They failed to upregulate a
      number of genes, including antimicrobial peptides, in response to infection. In
      particular, they also showed less specific immune expression patterns across
      individuals and colonies. These findings provide evidence for how immune
      responses on the individual-level vary with important elements of the environment
      and illustrate how nutrition can functionally alter not only general resistance,
      but also alter the pattern of specific host-parasite interactions. 

PMID- 24850922
TI  - Genetic recombination variation in wild Robertsonian mice: on the role of
      chromosomal fusions and Prdm9 allelic background.
AB  - Despite the existence of formal models to explain how chromosomal rearrangements
      can be fixed in a population in the presence of gene flow, few empirical data are
      available regarding the mechanisms by which genome shuffling contributes to
      speciation, especially in mammals. In order to shed light on this intriguing
      evolutionary process, here we present a detailed empirical study that shows how
      Robertsonian (Rb) fusions alter the chromosomal distribution of recombination
      events during the formation of the germline in a Rb system of the western house
      mouse (Mus musculus domesticus). Our results indicate that both the total number
      of meiotic crossovers and the chromosomal distribution of recombination events
      are reduced in mice with Rb fusions and that this can be related to alterations
      in epigenetic signatures for heterochromatinization. Furthermore, we detected
      novel house mouse Prdm9 allelic variants in the Rb system. Remarkably, mean
      recombination rates were positively correlated with a decrease in the number of
      ZnF domains in the Prdm9 gene. The suggestion that recombination can be modulated
      by both chromosomal reorganizations and genetic determinants that control the
      formation of double-stranded breaks during meiosis opens new avenues for
      understanding the role of recombination in chromosomal speciation. 

PMID- 24850923
TI  - Wheel running in the wild.
AB  - The importance of exercise for health and neurogenesis is becoming increasingly
      clear. Wheel running is often used in the laboratory for triggering enhanced
      activity levels, despite the common objection that this behaviour is an artefact
      of captivity and merely signifies neurosis or stereotypy. If wheel running is
      indeed caused by captive housing, wild mice are not expected to use a running
      wheel in nature. This however, to our knowledge, has never been tested. Here, we
      show that when running wheels are placed in nature, they are frequently used by
      wild mice, also when no extrinsic reward is provided. Bout lengths of running
      wheel behaviour in the wild match those for captive mice. This finding falsifies
      one criterion for stereotypic behaviour, and suggests that running wheel activity
      is an elective behaviour. In a time when lifestyle in general and lack of
      exercise in particular are a major cause of disease in the modern world, research
      into physical activity is of utmost importance. Our findings may help alleviate
      the main concern regarding the use of running wheels in research on exercise. 

PMID- 24850924
TI  - Insecticide exposure impacts vector-parasite interactions in insecticide
      resistant malaria vectors.
AB  - Currently, there is a strong trend towards increasing insecticide-based vector
      control coverage in malaria endemic countries. The ecological consequence of
      insecticide applications has been mainly studied regarding the selection of
      resistance mechanisms; however, little is known about their impact on vector
      competence in mosquitoes responsible for malaria transmission. As they have
      limited toxicity to mosquitoes owing to the selection of resistance mechanisms,
      insecticides may also interact with pathogens developing in mosquitoes. In this
      study, we explored the impact of insecticide exposure on Plasmodium falciparum
      development in insecticide-resistant colonies of Anopheles gambiae s.s.,
      homozygous for the ace-1 G119S mutation (Acerkis) or the kdr L1014F mutation
      (Kdrkis). Exposure to bendiocarb insecticide reduced the prevalence and intensity
      of P. falciparum oocysts developing in the infected midgut of the Acerkis strain,
      whereas exposure to dichlorodiphenyltrichloroethane reduced only the prevalence
      of P. falciparum infection in the Kdrkis strain. Thus, insecticide resistance
      leads to a selective pressure of insecticides on Plasmodium parasites, providing,
      to our knowledge, the first evidence of genotype by environment interactions on
      vector competence in a natural Anopheles-Plasmodium combination. Insecticide
      applications would affect the transmission of malaria in spite of resistance and
      would reduce to some degree the impact of insecticide resistance on malaria
      control interventions.

PMID- 24850925
TI  - Phylogenomic analysis of echinoderm class relationships supports Asterozoa.
AB  - While some aspects of the phylogeny of the five living echinoderm classes are
      clear, the position of the ophiuroids (brittlestars) relative to asteroids
      (starfish), echinoids (sea urchins) and holothurians (sea cucumbers) is
      controversial. Ophiuroids have a pluteus-type larva in common with echinoids
      giving some support to an ophiuroid/echinoid/holothurian clade named
      Cryptosyringida. Most molecular phylogenetic studies, however, support an
      ophiuroid/asteroid clade (Asterozoa) implying either convergent evolution of the
      pluteus or reversals to an auricularia-type larva in asteroids and holothurians.
      A recent study of 10 genes from four of the five echinoderm classes used
      'phylogenetic signal dissection' to separate alignment positions into subsets of
      (i) suboptimal, heterogeneously evolving sites (invariant plus rapidly changing)
      and (ii) the remaining optimal, homogeneously evolving sites. Along with most
      previous molecular phylogenetic studies, their set of heterogeneous sites,
      expected to be more prone to systematic error, support Asterozoa. The homogeneous
      sites, in contrast, support an ophiuroid/echinoid grouping, consistent with the
      cryptosyringid clade, leading them to posit homology of the ophiopluteus and
      echinopluteus. Our new dataset comprises 219 genes from all echinoderm classes;
      analyses using probabilistic Bayesian phylogenetic methods strongly support
      Asterozoa. The most reliable, slowly evolving quartile of genes also gives
      highest support for Asterozoa; this support diminishes in second and third
      quartiles and the fastest changing quartile places the ophiuroids close to the
      root. Using phylogenetic signal dissection, we find heterogenous sites support an
      unlikely grouping of Ophiuroidea + Holothuria while homogeneous sites again
      strongly support Asterozoa. Our large and taxonomically complete dataset finds no
      support for the cryptosyringid hypothesis; in showing strong support for the
      Asterozoa, our preferred topology leaves the question of homology of pluteus
      larvae open. 

PMID- 24850926
TI  - Looking beyond the hippocampus: old and new neurological targets for
      understanding memory disorders.
AB  - Although anterograde amnesia can occur after damage in various brain sites,
      hippocampal dysfunction is usually seen as the ultimate cause of the failure to
      learn new episodic information. This assumption is supported by anatomical
      evidence showing direct hippocampal connections with all other sites implicated
      in causing anterograde amnesia. Likewise, behavioural and clinical evidence would
      seem to strengthen the established notion of an episodic memory system emanating
      from the hippocampus. There is, however, growing evidence that key,
      interconnected sites may also regulate the hippocampus, reflecting a more
      balanced, integrated network that enables learning. Recent behavioural evidence
      strongly suggests that medial diencephalic structures have some mnemonic
      functions independent of the hippocampus, which can then act upon the
      hippocampus. Anatomical findings now reveal that nucleus reuniens and the
      retrosplenial cortex provide parallel, disynaptic routes for prefrontal control
      of hippocampal activity. There is also growing clinical evidence that
      retrosplenial cortex dysfunctions contribute to both anterograde amnesia and the
      earliest stages of Alzheimer's disease, revealing the potential significance of
      this area for clinical studies. This array of findings underlines the importance
      of redressing the balance and the value of looking beyond the hippocampus when
      seeking to explain failures in learning new episodic information. 

PMID- 24850927
TI  - A restatement of the natural science evidence base concerning neonicotinoid
      insecticides and insect pollinators.
AB  - There is evidence that in Europe and North America many species of pollinators
      are in decline, both in abundance and distribution. Although there is a long list
      of potential causes of this decline, there is concern that neonicotinoid
      insecticides, in particular through their use as seed treatments are, at least in
      part, responsible. This paper describes a project that set out to summarize the
      natural science evidence base relevant to neonicotinoid insecticides and insect
      pollinators in as policy-neutral terms as possible. A series of evidence
      statements are listed and categorized according to the nature of the underlying
      information. The evidence summary forms the appendix to this paper and an
      annotated bibliography is provided in the electronic supplementary material. 

PMID- 24850928
TI  - Hypoxia-inducible factor-1 mediates adaptive developmental plasticity of hypoxia
      tolerance in zebrafish, Danio rerio.
AB  - In recent years, natural and anthropogenic factors have increased aquatic hypoxia
      the world over. In most organisms, the cellular response to hypoxia is mediated
      by the master regulator hypoxia-inducible factor-1 (HIF-1). HIF-1 also plays a
      critical role in the normal development of the cardiovascular system of
      vertebrates. We tested the hypothesis that hypoxia exposures which resulted in
      HIF-1 induction during embryogenesis would be associated with enhanced hypoxia
      tolerance in subsequent developmental stages. We exposed zebrafish (Danio rerio)
      embryos to just 4 h of severe hypoxia or total anoxia at 18, 24 and 36 h post
      fertilization (hpf). Of these, exposure to hypoxia at 24 and 36 hpf as well as
      anoxia at 36 hpf activated the HIF-1 cellular pathway. Zebrafish embryos that
      acutely upregulated the HIF-1 pathway had an increased hypoxia tolerance as
      larvae. The critical window for hypoxia sensitivity and HIF-1 signalling was 24
      hpf. Adult male fish had a lower critical oxygen tension (Pcrit) compared with
      females. Early induction of HIF-1 correlated directly with an increased
      proportion of males in the population. We conclude that mounting a HIF-1 response
      during embryogenesis is associated with long-term impacts on the phenotype of
      later stages which could influence both individual hypoxia tolerance and
      population dynamics. 

PMID- 24850929
TI  - Severe recent decrease of adult body mass in a declining insectivorous bird
      population.
AB  - Migratory bird species that feed on air-borne insects are experiencing widespread
      regional declines, but these remain poorly understood. Agricultural
      intensification in the breeding range is often regarded as one of the main
      drivers of these declines. Here, we tested the hypothesis that body mass in
      breeding individuals should reflect habitat quality in an aerial insectivore, the
      tree swallow (Tachycineta bicolor), along a gradient of agricultural intensity.
      Our dataset was collected over 7 years (2005-2011) and included 2918 swallow
      captures and 1483 broods. Analyses revealed a substantial decline of the
      population over the course of the study (-19% occupancy rate), mirrored by
      decreasing body mass. This trend was especially severe in females, representing a
      total loss of 8% of their mass. Reproductive success was negatively influenced by
      intensive agriculture, but did not decrease over time. Interestingly, variation
      in body mass was independent of breeding habitat quality, leading us to suggest
      that this decline in body mass may result from carry-over effects from non
      breeding areas and affect population dynamics through reduced survival. This work
      contributes to the growing body of evidence suggesting that declines in migratory
      aerial insectivores are driven by multiple, complex factors requiring better
      knowledge of year-round habitat use. 

PMID- 24850930
TI  - The repeated evolution of large seeds on islands.
AB  - Several plant traits are known to evolve in predictable ways on islands. For
      example, herbaceous species often evolve to become woody and species frequently
      evolve larger leaves, regardless of growth form. However, our understanding of
      how seed sizes might evolve on islands lags far behind other plant traits. Here,
      we conduct the first test for macroevolutionary patterns of seed size on islands.
      We tested for differences in seed size between 40 island-mainland taxonomic
      pairings from four island groups surrounding New Zealand. Seed size data were
      collected in the field and then augmented by published seed descriptions to
      produce a more comprehensive dataset. Seed sizes of insular plants were
      consistently larger than mainland relatives, even after accounting for
      differences in growth form, dispersal mode and evolutionary history. Selection
      may favour seed size increases on islands to reduce dispersibility, as long
      distance dispersal may result in propagule mortality at sea. Alternatively,
      larger seeds tend to generate larger seedlings, which are more likely to
      establish and outcompete neighbours. Our results indicate there is a general
      tendency for the evolution of large seeds on islands, but the mechanisms
      responsible for this evolutionary pathway have yet to be fully resolved. 

PMID- 24850932
TI  - Where and how to search for evidence in the education literature: the WHEEL.
AB  - An awareness of how and where to search the education literature, and how to
      appraise it is essential to be a teacher scholar (an academic who takes a
      scholarly approach to teaching), to develop high quality education research, and
      to perform the scholarship of teaching and learning. Most pharmacy faculty
      scholars do not receive training in searching the education literature. Thus, a
      framework for searching the education literature is needed. The framework
      presented here on where and how to search for evidence in the education
      literature, referred to as the WHEEL for teaching, is meant to serve as a guide
      for faculty members in conducting comprehensive and exhaustive literature
      searches for the publication of scholarship of teaching and learning projects,
      educational research, or approaching one's teaching in a scholarly manner. Key
      resources to search and methods for searching the education literature are listed
      and described. 

PMID- 24850933
TI  - Cost savings associated with pharmacy student interventions during APPEs.
AB  - OBJECTIVE: To quantify the impact of pharmacy students' clinical interventions in
      terms of number and cost savings throughout advanced pharmacy practice
      experiences (APPEs) using a Web-based documentation program. METHODS: Five
      hundred eighty doctor of pharmacy (PharmD) students completing ten 4-week APPEs
      during the final year of the curriculum were asked to document all clinical
      interventions they made using a Web-based documentation tool. Data were collected
      over 4 academic years. RESULTS: The total number of interventions made was
      59,613, the total dollars saved was $8,583,681, and the average savings per
      intervention was $148. The top 3 categories of interventions made by students
      were identifying dosing issues, conducting chart reviews, and recommending
      appropriate therapy. The top 3 intervention types made by students that resulted
      in the most dollars saved per intervention were identifying potential allergic
      reactions, identifying drug interactions, and resolving contraindications.
      CONCLUSIONS: Pharmacy students made important and cost-effective clinical
      interventions during their APPEs that resulted in significant savings.
      Documentation programs can track the number, type, and value of the interventions
      that pharmacy students are making.

PMID- 24850934
TI  - Status of pharmacy practice experience education programs.
AB  - OBJECTIVE: To assess financial, personnel, and curricular characteristics of US
      pharmacy practice experiential education programs and follow-up on results of a
      similar survey conducted in 2001. METHODS: Experiential education directors at
      118 accredited US pharmacy colleges and schools were invited to participate in a
      blinded, Web-based survey in 2011. Aggregate responses were analyzed using
      descriptive statistics and combined with data obtained from the American
      Association of Colleges of Pharmacy to assess program demographics, faculty and
      administrative organizational structure, and financial support. RESULTS: The
      number of advanced pharmacy practice experience (APPE) sites had increased by 24%
      for medium, 50% for large, and 55% for very large colleges and schools.
      Introductory pharmacy practice experience (IPPE) sites outnumbered APPEs twofold.
      The average experiential education team included an assistant/associate dean (0.4
      full-time equivalent [FTE]), a director (1.0 FTE), assistant/associate director
      (0.5 FTE), coordinator (0.9 FTE), and multiple administrative assistants (1.3
      FTE). Most faculty members (63%-75%) were nontenure track and most coordinators
      (66%) were staff members. Estimated costs to operate an experiential education
      program represented a small percentage of the overall expense budget of pharmacy
      colleges and schools. CONCLUSION: To match enrollment growth, pharmacy practice
      experiential education administrators have expanded their teams, reorganized
      responsibilities, and found methods to improve cost efficiency. These benchmarks
      will assist experiential education administrators to plan strategically for
      future changes.

PMID- 24850935
TI  - Association of Health Sciences Reasoning Test scores with academic and
      experiential performance.
AB  - OBJECTIVES: To assess the association of scores on the Health Sciences Reasoning
      Test (HSRT) with academic and experiential performance in a doctor of pharmacy
      (PharmD) curriculum. METHODS: The HSRT was administered to 329 first-year (P1)
      PharmD students. Performance on the HSRT and its subscales was compared with
      academic performance in 29 courses throughout the curriculum and with performance
      in advanced pharmacy practice experiences (APPEs). RESULTS: Significant positive
      correlations were found between course grades in 8 courses and HSRT overall
      scores. All significant correlations were accounted for by pharmaceutical care
      laboratory courses, therapeutics courses, and a law and ethics course.
      CONCLUSION: There was a lack of moderate to strong correlation between HSRT
      scores and academic and experiential performance. The usefulness of the HSRT as a
      tool for predicting student success may be limited.

PMID- 24850936
TI  - Student and faculty member perspectives on lecture capture in pharmacy education.
AB  - OBJECTIVES: To examine faculty members' and students' use and perceptions of
      lecture recordings in a previously implemented lecture-capture initiative.
      METHODS: Patterns of using lecture recordings were determined from software
      analytics, and surveys were conducted to determine awareness and usage, effect on
      attendance and other behaviors, and learning impact. RESULTS: Most students and
      faculty members were aware of and appreciated the recordings. Students' patterns
      of use changed as the novelty wore off. Students felt that the recordings
      enhanced their learning, improved their in-class engagement, and had little
      effect on their attendance. Faculty members saw little difference in students'
      grades or in-class engagement but noted increased absenteeism. CONCLUSION:
      Students made appropriate use of recordings to support their learning, but
      faculty members generally did not make active educational use of the recordings.
      Further investigation is needed to understand the effects of lecture recordings
      on attendance. Professional development activities for both students and faculty
      members would help maximize the learning benefits of the recordings.

PMID- 24850937
TI  - Perceptions of tenure and tenure reform in academic pharmacy.
AB  - OBJECTIVES: To determine the academic pharmacy community's perceptions of and
      recommendations for tenure and tenure reform. METHODS: A survey instrument was
      administered via either a live interview or an online survey instrument to
      selected members of the US academic pharmacy community. RESULTS: The majority of
      respondents felt that tenure in academic pharmacy was doing what it was intended
      to do, which is to provide academic freedom and allow for innovation (59.6%).
      Respondents raised concern over the need for faculty mentoring before and after
      achieving tenure, whether tenure adequately recognized service, and that tenure
      was not the best standard for recognition and achievement. The majority (63%)
      agreed that tenure reform was needed in academic pharmacy, with the most
      prevalent recommendation being to implement post-tenure reviews. Some disparities
      in opinions of tenure reform were seen in the subgroup analyses of clinical
      science vs basic science faculty members, public vs private institutions, and
      administrators vs nonadministrators. CONCLUSIONS: The majority of respondents
      want to see tenure reformed in academic pharmacy.

PMID- 24850938
TI  - Online virtual-patient cases versus traditional problem-based learning in
      advanced pharmacy practice experiences.
AB  - OBJECTIVE: To evaluate the efficacy of faculty-led problem-based learning (PBL)
      vs online simulated-patient case in fourth-year (P4) pharmacy students. DESIGN:
      Fourth-year pharmacy students were randomly assigned to participate in either
      online branched-case learning using a virtual simulation platform or a small
      group discussion. Preexperience and postexperience student assessments and a
      survey instrument were completed. EVALUATION: While there were no significant
      differences in the preexperience test scores between the groups, there was a
      significant increase in scores in both the virtual-patient group and the PBL
      group between the preexperience and postexperience tests. The PBL group had
      higher postexperience test scores (74.8+/-11.7) than did the virtual-patient
      group (66.5+/-13.6) (p=0.001). CONCLUSION: The PBL method demonstrated
      significantly greater improvement in postexperience test scores than did the
      virtual-patient method. Both were successful learning methods, suggesting that a
      diverse approach to simulated patient cases may reach more student learning
      styles.

PMID- 24850939
TI  - A multipreceptor approach to ambulatory care topic discussions.
AB  - OBJECTIVE: To assess the impact of a multipreceptor approach to facilitating
      topic discussions on students' knowledge and confidence in clinical decision
      making during an ambulatory care advanced pharmacy practice experiences (APPEs).
      DESIGN: Faculty members with relevant expertise and experience facilitated
      discussions with fourth-year doctor of pharmacy (PharmD) students regarding 7
      ambulatory care topics. A student self-assessment survey and knowledge-assessment
      instrument was administered before and after discussions. ASSESSMENT: Students'
      examination scores increased significantly from 59.1% +/- 13.9% at baseline to
      76.5% +/- 12.6% at the end of the 5-week experience (p<0.001). The majority of
      participants were comfortable making therapeutic decisions regarding medication
      use as it related to all discussion topics except heart failure. CONCLUSIONS:
      Participation in topic discussions led by faculty members with expertise and
      experience for each ambulatory care topic was associated with a significant
      improvement in knowledge-assessment scores.

PMID- 24850940
TI  - An elective course on dermatological topics and cosmeceutical compounding.
AB  - OBJECTIVE: To implement and assess a pharmacy dermatology and cosmeceutical
      compounding elective course and its impact on graduates' careers. DESIGN: A 3
      credit elective course that incorporated classroom lectures on ambulatory
      dermatologic diseases and cosmeceutical products with case studies, weekly
      quizzes, and a comprehensive business plan project was implemented in a doctor of
      pharmacy (PharmD) program in 2010. ASSESSMENT: Assessment instruments including
      weekly quizzes, a business plan project, and pre- and post-course tests were used
      to evaluate course content. Across 3 offerings of the course (2010, 2011, 2012),
      pre- and post-course test scores improved. Results of a postgraduate survey
      showed that 54% of respondents worked at a pharmacy offering compounding
      services, and 57% felt that the course played a significant or very significant
      role in their counseling on dermatologic conditions. CONCLUSIONS: Assessment
      methods revealed student learning of course content and the course appeared
      moderately beneficial to graduates' early careers. A more longitudinal analysis
      is needed to assess the course's impact on long-term career choices, particularly
      those dealing with compounding of cosmeceutical products.

PMID- 24850941
TI  - An elective course in aromatherapy science.
AB  - OBJECTIVE: To evaluate the impact of an innovative team-taught elective course on
      second-year (P2) students' knowledge and skills relating to the relationship
      between aromatherapy and pharmacy. DESIGN: An Aromatherapy Science elective
      course was offered to P2 students in an accelerated doctor of pharmacy (PharmD)
      degree program and was designed to provide an elective course experience while
      focusing on active-learning skills such as group work, student-led presentations,
      and in-class activities. Lectures were designed to reinforce core curricular
      threads from the basic sciences within the pharmaceutical sciences department
      while highlighting key aromatherapy principles. ASSESSMENT: Course evaluations,
      grades, and student self-assessments were used to evaluate student fulfillment
      and knowledge gained. Students agreed this hands-on course integrated
      pharmaceutical science experiences, enriched their pharmacy education, and
      provided knowledge to enhance their confidence in describing essential oil uses,
      drug interactions, and key aromatherapy clinical implications. CONCLUSION:
      Students agreed this course prepared them to identify essential oil therapeutic
      uses and potential essential oil-drug interactions, and interpret literature. The
      introduction of aromatherapy principles to pharmacy students will prepare a new
      generation of healthcare professionals on the role of alternative medicines.

PMID- 24850942
TI  - An interprofessional faculty seminar focused on interprofessional education.
AB  - OBJECTIVE: To evaluate an interprofessional faculty seminar designed to explore
      the topic of interprofessional education (IPE) as a way to encourage dialogue and
      identify opportunities for collaboration among health professional programs.
      DESIGN: A seminar was developed with the schools of pharmacy, nursing, dental
      medicine, and medicine. Components included a review of IPE presentation, poster
      session highlighting existing IPE endeavors, discussion of future opportunities,
      and thematic round tables on how to achieve IPE competencies. ASSESSMENT: Fifty
      four health professions faculty members attended the seminar. Significant
      differences in knowledge related to the IPE seminar were identified. Responses to
      a perception survey indicated that seminar goals were achieved. CONCLUSION: An
      interprofessional faculty seminar was well received and achieved its goals.
      Participants identified opportunities and networked for future collaborations.

PMID- 24850943
TI  - A transgender health care panel discussion in a required diversity course.
AB  - OBJECTIVES: To examine the impact of a panel discussion on transgender health
      care on first-year (P1) pharmacy students' knowledge and understanding of
      transgender experiences in an Introduction to Diversity course. DESIGN: The panel
      consisted of both transgender males and females. After panelists shared their
      healthcare experiences, students asked them questions in a moderated setting.
      Students completed evaluations on the presentation and learning outcomes. They
      also wrote a self-reflection paper on the experience. ASSESSMENT: Ninety-one
      percent of students agreed that they could describe methods for showing respect
      to a transgender patient and 91.0% evaluated the usefulness of the presentation
      to be very good or excellent. Qualitative analysis (phenomenological study) was
      conducted on the self-reflection papers and revealed 7 major themes. CONCLUSION:
      First-year students reported that they found the panel discussion to be eye
      opening and relevant to their pharmacy career. Our panel may serve as model for
      other pharmacy schools to implement.

PMID- 24850944
TI  - Evaluation of an injection training and certification program for pharmacy
      students.
AB  - OBJECTIVE: To evaluate an injection training and certification program for third
      year (P3) pharmacy students, and to measure the impact of students'
      administration of immunizations at an influenza clinic on their knowledge,
      skills, and competence in immunization. DESIGN: A repeated measures design was
      used to assess students' injection skills across the injection training and
      certification program and the influenza clinic. A repeated measures design was
      also used to evaluate students' self-reported knowledge, experience, and
      confidence. ASSESSMENT: Postcertification and during influenza clinic comparisons
      showed significant improvement in students' knowledge, experience, and confidence
      after taking part in the influenza clinic. University staff members and students
      indicated in a survey that they were satisfied with the clinic services provided
      by pharmacy students. CONCLUSION: The injection training and certification
      program and the university influenza clinic were effective in enhancing and
      fostering student skills development.

PMID- 24850945
TI  - Effectiveness of E-learning in pharmacy education.
AB  - Over the past 2 decades, e-learning has evolved as a new pedagogy within pharmacy
      education. As learners and teachers increasingly seek e-learning opportunities
      for an array of educational and individual benefits, it is important to evaluate
      the effectiveness of these programs. This systematic review of the literature
      examines the quality of e-learning effectiveness studies in pharmacy, describes
      effectiveness measures, and synthesizes the evidence for each measure. E-learning
      in pharmacy education effectively increases knowledge and is a highly acceptable
      instructional format for pharmacists and pharmacy students. However, there is
      limited evidence that e-learning effectively improves skills or professional
      practice. There is also no evidence that e-learning is effective at increasing
      knowledge long term; thus, long-term follow-up studies are required.
      Translational research is also needed to evaluate the benefits of e-learning at
      patient and organizational levels. 

PMID- 24850946
TI  - In response to "use of humor to enhance learning: Bull's eye or off the mark".

PMID- 24850947
TI  - Student perspectives on student leadership development programs.

PMID- 24850948
TI  - Impact of a student leadership development program.

PMID- 24850949
TI  - Active learning should not be one-size-fits-all for foundation knowledge courses.

PMID- 24850952
TI  - Neocortical synchronization.
AB  - Neuronal synchronization occurs when two or more neuronal events are coordinated
      across time. Local synchronization produces field potentials. Long-range
      synchronization between distant brain sites contributes to the
      electroencephalogram. Neuronal synchronization depends on synaptic
      (chemical/electrical), ephaptic, and extracellular interactions. For an expanded
      treatment of this topic see Jasper's Basic Mechanisms of the Epilepsies, Fourth
      Edition (Noebels JL, Avoli M, Rogawski MA, Olsen RW, Delgado-Escueta AV, eds)
      published by Oxford University Press (available on the National Library of
      Medicine Bookshelf [NCBI] at www.ncbi.nlm.nih.gov/books).

PMID- 24850953
TI  - CFD simulation of water vapour condensation in the presence of non-condensable
      gas in vertical cylindrical condensers.
AB  - This paper presents the simulation of the condensation of water vapour in the
      presence of non-condensable gas using computational fluid dynamics (CFD) for
      turbulent flows in a vertical cylindrical condenser tube. The simulation accounts
      for the turbulent flow of the gas mixture, the condenser wall and the turbulent
      flow of the coolant in the annular channel with no assumptions of constant wall
      temperature or heat flux. The condensate film is assumed to occupy a negligible
      volume and its effect on the condensation of the water vapour has been taken into
      account by imposing a set of boundary conditions. A new strategy is used to
      overcome the limitation of the currently available commercial CFD package to
      solve the simultaneous simulation of flows involving multispecies and fluids of
      gas and liquid in separate channels. The results from the CFD simulations are
      compared with the experimental results from the literature for the condensation
      of water vapour with air as the non-condensable gas and for inlet mass fraction
      of the water vapour from 0.66 to 0.98. The CFD simulation results in general
      agree well with the directly measured quantities and it is found that the
      variation of heat flux in the condenser tube is more complex than a simple
      polynomial curve fit. The CFD results also show that, at least for flows
      involving high water vapour content, the axial velocity of the gas mixture at the
      interface between the gas mixture and the condensate film is in general not small
      and cannot be neglected.

PMID- 24850951
TI  - Structure and function of atypically coordinated enzymatic mononuclear non-heme
      Fe(II) centers.
AB  - Mononuclear, non-heme-Fe(II) centers are key structures in O2 metabolism and
      catalyze an impressive variety of enzymatic reactions. While most are bound via
      two histidines and a carboxylate, some show a different organization. A short
      overview of atypically coordinated O2 dependent mononuclear-non-heme-Fe(II)
      centers is presented here Enzymes with 2-His, 3-His, 3-His-carboxylate and 4-His
      bound Fe(II) centers are discussed with a focus on their reactivity, metal ion
      promiscuity and recent progress in the elucidation of their enzymatic mechanisms.
      Observations concerning these and classically coordinated Fe(II) centers are used
      to understand the impact of the metal binding motif on catalysis.

PMID- 24850954
TI  - Current status of taeniasis and cysticercosis in Vietnam.
AB  - Several reports on taeniasis and cysticercosis in Vietnam show that they are
      distributed in over 50 of 63 provinces. In some endemic areas, the prevalence of
      taeniasis was 0.2-12.0% and that of cysticercosis was 1.0-7.2%. The major
      symptoms of taeniasis included fidgeted anus, proglottids moving out of the anus,
      and proglottids in the feces. Clinical manifestations of cysticercosis in humans
      included subcutaneous nodules, epileptic seizures, severe headach, impaired
      vision, and memory loss. The species identification of Taenia in Vietnam included
      Taenia asiatica, Taenia saginata, and Taenia solium based on combined morphology
      and molecular methods. Only T. solium caused cysticercosis in humans.
      Praziquantel was chosen for treatment of taeniasis and albendazole for treatment
      of cysticercosis. The infection rate of cysticercus cellulosae in pigs was 0.04%
      at Hanoi slaughterhouses, 0.03-0.31% at provincial slaughterhouses in the north,
      and 0.9% in provincial slaughterhouses in the southern region of Vietnam. The
      infection rate of cysticercus bovis in cattle was 0.03-2.17% at Hanoi
      slaughterhouses. Risk factors investigated with regard to transmission of Taenia
      suggested that consumption of raw meat (eating raw meat 4.5-74.3%), inadequate or
      absent meat inspection and control, poor sanitation in some endemic areas, and
      use of untreated human waste as a fertilizer for crops may play important roles
      in Vietnam, although this remains to be validated. 

PMID- 24850955
TI  - Down-regulation of cellulose synthase inhibits the formation of endocysts in
      Acanthamoeba.
AB  - Acanthamoeba cysts are resistant to unfavorable physiological conditions and
      various disinfectants. Acanthamoeba cysts have 2 walls containing various sugar
      moieties, and in particular, one third of the inner wall is composed of
      cellulose. In this study, it has been shown that down-regulation of cellulose
      synthase by small interfering RNA (siRNA) significantly inhibits the formation of
      mature Acanthamoeba castellanii cysts. Calcofluor white staining and transmission
      electron microscopy revealed that siRNA transfected amoeba failed to form an
      inner wall during encystation and thus are likely to be more vulnerable. In
      addition, the expression of xylose isomerase, which is involved in cyst wall
      formation, was not altered in cellulose synthase down-regulated amoeba,
      indicating that cellulose synthase is a crucial factor for inner wall formation
      by Acanthamoeba during encystation. 

PMID- 24850956
TI  - Evaluation of recombinant SAG1, SAG2, and SAG3 antigens for serodiagnosis of
      toxoplasmosis.
AB  - Serologic tests are widely accepted for diagnosing Toxoplasma gondii but
      purification and standardization of antigen needs to be improved. Recently,
      surface tachyzoite and bradyzoite antigens have become more attractive for this
      purpose. In this study, diagnostic usefulness of 3 recombinant antigens (SAG1,
      SAG2, and SAG3) were evaluated, and their efficacy was compared with the
      available commercial ELISA. The recombinant plasmids were transformed to JM109
      strain of Escherichia coli, and the recombinants were expressed and purified.
      Recombinant SAG1, SAG2, and SAG3 antigens were evaluated using different groups
      of sera in an ELISA system, and the results were compared to those of a
      commercial IgG and IgM ELISA kit. The sensitivity and specificity of recombinant
      surface antigens for detection of anti-Toxoplasma IgG in comparison with
      commercially available ELISA were as follows: SAG1 (93.6% and 92.9%), SAG2
      (100.0% and 89.4%), and SAG3 (95.4% and 91.2%), respectively. A high degree of
      agreement (96.9%) was observed between recombinant SAG2 and commercial ELISA in
      terms of detecting IgG anti-Toxoplasma antibodies. P22 had the best performance
      in detecting anti-Toxoplasma IgM in comparison with the other 2 recombinant
      antigens. Recombinant SAG1, SAG2, and SAG3 could all be used for diagnosis of IgG
      specific antibodies against T. gondii. 

PMID- 24850957
TI  - Probability of antibody formation against circumsporozoite protein of Plasmodium
      vivax among Korean malaria patients.
AB  - To evaluate the seroprevalence against circumsporozoite protein (CSP) of
      Plasmodium vivax in sera of Korean patients, the central repeating domain (CRD)
      of CSP was cloned and analyzed. From the genomic DNA of patient's blood, 2 kinds
      of CSPs were identified to belong to a VK210 type, which is the dominant
      repeating of GDRA(D/A)GQPA, and named as PvCSPA and PvCSPB. Recombinantly
      expressed his-tagged PvCSPA or PvCSPB in Escherichia coli reacted well against
      sera of patients in western blot, with the detecting rate of 47.9% (58/121),
      which included 15 cases positive for PvCSPA, 6 cases positive for PvCSPB, and 37
      cases for both. The mixture of PvCSPA and PvCSPB was loaded to a rapid diagnostic
      test kit (RDT) and applied with the same set of patient sera, which resulted in
      detection rates of 57.0% (69/121). When the protein sequences of PvCSPA were
      compared with those of P. vivax in endemic regions of India and Uganda, they were
      compatibly homologous to PvCSPA with minor mutations. These results suggested
      that the recombinant PvCSPA and PvCSPB loaded RDT may be a milestone in latent
      diagnosis which has been a hot issue of domestic malaria and important for
      radical therapy in overlapped infections with P. falciparum in tropical and
      subtropical areas. During the biological process of malarial infection, exposure
      of CSP to antigen-antibody reaction up to 57.0% is the first report in Korea. 

PMID- 24850958
TI  - Ameliorative effect of bone marrow-derived stem cells on injured liver of mice
      infected with Schistosoma mansoni.
AB  - The technique of stem cells or hepatocytes transplantation has recently improved
      in order to bridge the time before whole-organ liver transplantation. In the
      present study, unfractionated bone marrow stem cells (BMSCs) were harvested from
      the tibial and femoral marrow compartments of male mice, which were cultured in
      Dulbecco's modified Eagle's medium (DMEM) with and without hepatocyte growth
      factor (HGF), and then transplanted into Schistosoma mansoni-infected female mice
      on their 8th week post-infection. Mice were sacrificed monthly until the third
      month of bone marrow transplantation, serum was collected, and albumin
      concentration, ALT, AST, and alkaline phosphatase (ALP) activities were assayed.
      On the other hand, immunohistopathological and immunohistochemical changes of
      granuloma size and number, collagen content, and cells expressing OV-6 were
      detected for identification of liver fibrosis. BMSCs were shown to differentiate
      into hepatocyte-like cells. Serum ALT, AST, and ALP were markedly reduced in the
      group of mice treated with BMSCs than in the untreated control group. Also,
      granuloma showed a marked decrease in size and number as compared to the BMSCs
      untreated group. Collagen content showed marked decrease after the third month of
      treatment with BMSCs. On the other hand, the expression of OV-6 increased
      detecting the presence of newly formed hepatocytes after BMSCs treatment. BMSCs
      with or without HGF infusion significantly enhanced hepatic regeneration in S.
      mansoni-induced fibrotic liver model and have pathologic and
      immunohistopathologic therapeutic effects. Also, this new therapeutic trend could
      generate new hepatocytes to improve the overall liver functions. 

PMID- 24850959
TI  - Sequence analysis and molecular characterization of Wnt4 gene in metacestodes of
      Taenia solium.
AB  - Wnt proteins are a family of secreted glycoproteins that are evolutionarily
      conserved and considered to be involved in extensive developmental processes in
      metazoan organisms. The characterization of wnt genes may improve understanding
      the parasite's development. In the present study, a wnt4 gene encoding 491amino
      acids was amplified from cDNA of metacestodes of Taenia solium using reverse
      transcription PCR (RT-PCR). Bioinformatics tools were used for sequence analysis.
      The conserved domain of the wnt gene family was predicted. The expression profile
      of Wnt4 was investigated using real-time PCR. Wnt4 expression was found to be
      dramatically increased in scolex evaginated cysticerci when compared to
      invaginated cysticerci. In situ hybridization showed that wnt4 gene was
      distributed in the posterior end of the worm along the primary body axis in
      evaginated cysticerci. These findings indicated that wnt4 may take part in the
      process of cysticerci evagination and play a role in scolex/bladder development
      of cysticerci of T. solium. 

PMID- 24850960
TI  - Molecular Identification of Haemadipsa rjukjuana (Hirudiniformes: Haemadipsidae)
      in Gageo Island, Korea.
AB  - There are 60 species of blood-feeding land leeches, 50 species belonging to the
      family Haemadipsidae and 10 species belonging to the family Xerobdellidae.
      Despite recent papers on the land leeches, their taxonomic identification is not
      fully understood, especially at a species level. In Korea, there have been no
      historical records of the terrestrial leeches, but recently an unrecorded blood
      feeding land leech was discovered at Gageo-do (Island), Korea. Molecular analysis
      was used to identify the species of 29 leeches collected from Mt. Dock-Sil in
      Gageo-do. Conventional PCR was conducted using nuclear 18S rRNA and mitochondrial
      cytochrome c oxidase subunit 1 (CO1) genetic marker. The 18S rRNA sequences
      revealed that the leeches share 99.9% identity with Haemadipsa rjukjuana
      (inhabiting Taiwan), and the CO1 sequences revealed that the leeches are very
      close to H. rjukjuana (inhabiting Taiwan). The CO1 sequences were separated into
      2 categories, 1 with 94.6% and the other with 94.3% similarity to the H.
      rjukjuana L00115A (inhabiting Taiwan). This new finding of the land leech is the
      first record in Korea. In addition, the north range of the distribution of the
      blood-feeding leech (Hirudiniformes: Haemadipisidae) should be reconsidered
      including Korea. 

PMID- 24850961
TI  - Comparative analysis of pathogenic organisms in cockroaches from different
      community settings in Edo State, Nigeria.
AB  - Cockroaches are abundant in Nigeria and are seen to harbour an array of
      pathogens. Environmental and sanitary conditions associated with
      demographic/socio-economic settings of an area could contribute to the prevalence
      of disease pathogens in cockroaches. A total of 246 cockroaches (Periplaneta
      americana) in urban (Benin, n=91), semi-urban (Ekpoma, n=75) and rural (Emuhi,
      n=70) settings in Edo State, Nigeria were collected within and around households.
      The external body surfaces and alimentary canal of these cockroaches were
      screened for bacterial, fungal, and parasitological infections. Bacillus sp. and
      Escherichia coli were the most common bacteria in cockroaches. However,
      Enterococcus faecalis could not be isolated in cockroaches trapped from Ekpoma
      and Emuhi. Aspergillus niger was the most prevalent fungus in Benin and Ekpoma,
      while Mucor sp. was predominant in Emuhi. Parasitological investigations revealed
      the preponderance of Ascaris lumbricoides in Benin and Emuhi, while Trichuris
      trichura was the most predominant in Ekpoma. The prevalence and burden of
      infection in cockroaches is likely to be a reflection of the sanitary conditions
      of these areas. Also, cockroaches in these areas making incursions in homes may
      increase the risk of human infections with these disease agents. 

PMID- 24850962
TI  - Detection of heparin in the salivary gland and midgut of Aedes togoi.
AB  - Mosquitoes secrete saliva that contains biological substances, including
      anticoagulants that counteract a host's hemostatic response and prevent blood
      clotting during blood feeding. This study aimed to detect heparin, an
      anticoagulant in Aedes togoi using an immunohistochemical detection method, in
      the salivary canal, salivary gland, and midgut of male and female mosquitoes.
      Comparisons showed that female mosquitoes contained higher concentrations of
      heparin than male mosquitoes. On average, the level of heparin was higher in
      blood-fed female mosquitoes than in non-blood-fed female mosquitoes. Heparin
      concentrations were higher in the midgut than in the salivary gland. This
      indicates presence of heparin in tissues of A. togoi. 

PMID- 24850963
TI  - Visceral leishmaniasis without fever in an 11-month-old infant: a rare clinical
      feature of Kala-azar.
AB  - Visceral leishmaniasis or kala-azar is an endemic parasitic disease in some parts
      of the world which is characterized by fever, splenomegaly, and pancytopenia in
      most of the cases. Herein we report an 11 month-old male infant with diagnosis of
      kala-azar who presented with pallor, hepatosplenomegaly, failure to gain weight,
      and no history of fever. Surprisingly, fever started after beginning of meglumine
      antimoniate treatment in this patient. As far as we are aware of, this is a rare
      presentation of visceral leishmaniasis. Therefore, clinicians especially in
      endemic areas are highly recommended to include kala-azar among differential
      diagnosis of unexplained anemia without fever to prevent misdiagnosis of this
      potentially fatal, but treatable condition. 

PMID- 24850964
TI  - A case of Fasciola hepatica infection mimicking cholangiocarcinoma and ITS-1
      sequencing of the worm.
AB  - Fascioliasis is a zoonotic infection caused by Fasciola hepatica or Fasciola
      gigantica. We report an 87-year-old Korean male patient with postprandial
      abdominal pain and discomfort due to F. hepatica infection who was diagnosed and
      managed by endoscopic retrograde cholangiopancreatography (ERCP) with extraction
      of 2 worms. At his first visit to the hospital, a gallbladder stone was
      suspected. CT and magnetic retrograde cholangiopancreatography (MRCP) showed an
      intraductal mass in the common bile duct (CBD) without proximal duct dilatation.
      Based on radiological findings, the presumed diagnosis was intraductal
      cholangiocarcinoma. However, in ERCP which was performed for biliary
      decompression and tissue diagnosis, movable materials were detected in the CBD.
      Using a basket, 2 living leaf-like parasites were removed. The worms were
      morphologically compatible with F. hepatica. To rule out the possibility of the
      worms to be another morphologically close species, in particular F. gigantica, 1
      specimen was processed for genetic analysis of its ITS-1 region. The results
      showed that the present worms were genetically identical (100%) with F. hepatica
      but different from F. gigantica. 

PMID- 24850965
TI  - Two human cases of Diphyllobothrium nihonkaiense infection in Korea.
AB  - Diphyllobothrium latum and Diphyllobothrium nihonkaiense are the 2 reported main
      causes of human diphyllobothriasis in the Republic of Korea. However, the
      differentiation of these 2 species based on morphologic features alone is
      difficult. The authors used nucleotide sequencing of the mitochondrial cytochrome
      c oxidase subunit 1 (cox1) gene to diagnose Diphyllobothrium spp. Two patients
      visited the emergency room at Kyungpook National University Hospital on 3 April
      and 12 April 2013, respectively, with fragments of parasites found while
      defecating. The parasites were identified as Diphyllobothrium spp. based on
      morphologic characteristics, and subsequent cox1 gene sequencing showed 99.9%
      similarity (1,478/1,480 bp) with D. nihonkaiense. Our findings support the
      hypothesis that D. nihonkaiense is a dominant species in Korea. 

PMID- 24850966
TI  - Metagonimus yokogawai: a 100-kDa somatic antigen commonly reacting with other
      trematodes.
AB  - This study was undertaken to characterize the properties of a 100 kDa somatic
      antigen from Metagonimus yokogawai. Monoclonal antibodies (mAbs) were produced
      against this 100 kDa antigen, and their immunoreactivity was assessed by western
      blot analysis with patients' sera. The mAbs against the 100 kDa antigen commonly
      reacted with various kinds of trematode antigens, including intestinal
      (Gymnophalloides seoi), lung (Paragonimus westermani), and liver flukes
      (Clonorchis sinensis and Fasciola hepatica). However, this mAb showed no cross
      reactions with other helminth parasites, including nematodes and cestodes. To
      determine the topographic distribution of the 100 kDa antigen in worm sections,
      indirect immunoperoxidase staining was performed. A strong positive reaction was
      observed in the tegumental and subtegumental layers of adult M. yokogawai and C.
      sinensis. The results showed that the 100 kDa somatic protein of M. yokogawai is
      a common antigen which recognizes a target epitope present over the tegumental
      layer of different trematode species. 

PMID- 24850967
TI  - Sequence analysis of cytb gene in Echinococcus granulosus from Western China.
AB  - Echinococcus granulosus is the causative agent of cystic echinococcosis with
      medical and veterinary importance in China. Our main objective was to discuss the
      genotypes and genetic diversity of E. granulosus present in domestic animals and
      humans in western China. A total of 45 hydatid cyst samples were collected from
      sheep, humans, and a yak and subjected to an analysis of the sequences of
      mitochondrial cytochrome b (cytb) gene. The amplified PCR product for all samples
      was a 1,068 bp band. The phylogenetic analysis showed that all 45 samples were
      identified as E. granulosus (genotype G1). Ten haplotypes were detected among the
      samples, with the main haplotype being H1. The haplotype diversity was 0.626,
      while the nucleotide diversity was 0.001. These results suggested that genetic
      diversity was low among our samples collected from the west of China based on
      cytb gene analysis. These findings may provide more information on molecular
      characteristics of E. granulosus from this Chinese region. 

PMID- 24850968
TI  - Recent situation of taeniasis in Mongolia (2002-2012).
AB  - Epidemiological situation of taeniasis in Mongolia was assessed based on
      mitochondrial DNA identification of the parasite species. Multiplex PCR was used
      on a total of 194 proglottid specimens of Taenia species and copro-PCR and loop
      mediated isothermal amplification (LAMP) assays were utilized for detection of
      copro-DNA of 37 fecal samples from taeniasis patients submitted to the Mongolian
      National Center for Communicable Diseases (NCCD) from 2002 to 2012. In addition,
      4 out of 44 calcified cysts in beef kept in formalin since 2003 were evaluated
      for histopathological confirmation of cattle cysticercosis. All proglottid
      specimens and stool samples were confirmed to be Taenia saginata by multiplex PCR
      and by copro-PCR and LAMP, respectively. Cysts collected from cattle were
      morphologically confirmed to be metacestodes of Taenia species. T. saginata
      taeniasis was identified from almost all ages from a 2-year-old boy up to a 88
      year-old woman and most prominently in 15-29 age group (37%, 74/198) followed by
      30-44 age group (34.8%, 69/198 ) from 15 of Mongolia's 21 provinces, while cattle
      cysticerci were found from 12 provinces. The highest proportion of taeniasis
      patients was in Ulaanbaatar, the capital of Mongolia. 

PMID- 24850969
TI  - Parasitic infections based on 320 clinical samples submitted to Hanyang
      University, Korea (2004-2011).
AB  - We analyzed 320 clinical samples of parasitic infections submitted to the
      Department of Environmental Biology and Medical Parasitology, Hanyang University
      from January 2004 to June 2011. They consisted of 211 nematode infections, 64
      trematode or cestode infections, 32 protozoan infections, and 13 infections with
      arthropods. The nematode infections included 67 cases of trichuriasis, 62 of
      anisakiasis (Anisakis sp. and Pseudoterranova decipiens), 40 of enterobiasis, and
      24 of ascariasis, as well as other infections including strongyloidiasis,
      thelaziasis, loiasis, and hookworm infecions. Among the cestode or trematode
      infections, we observed 27 cases of diphyllobothriasis, 14 of sparganosis, 9 of
      clonorchiasis, and 5 of paragonimiasis together with a few cases of taeniasis
      saginata, cysticercosis cellulosae, hymenolepiasis, and echinostomiasis. The
      protozoan infections included 14 cases of malaria, 4 of cryptosporidiosis, and 3
      of trichomoniasis, in addition to infections with Entamoeba histolytica,
      Entamoeba dispar, Entamoeba coli, Endolimax nana, Giardia lamblia, and Toxoplasma
      gondii. Among the arthropods, we detected 6 cases of Ixodes sp., 5 of Phthirus
      pubis, 1 of Sarcoptes scabiei, and 1 of fly larva. The results revealed that
      trichuriasis, anisakiasis, enterobiasis, and diphyllobothriasis were the most
      frequently found parasitosis among the clinical samples. 

PMID- 24850970
TI  - No detection of severe Fever with thrombocytopenia syndrome virus from ixodid
      ticks collected in seoul.
AB  - Larvae, nymphs, and adult stages of 3 species of ixodid ticks were collected by
      tick drag methods in Seoul during June-October 2013, and their infection status
      with severe fever with thrombocytopenia syndrome (SFTS) virus was examined using
      RT-PCR. During the period, 732 Haemaphysalis longicornis, 62 Haemaphysalis flava,
      and 2 Ixodes nipponensis specimens were collected. Among the specimens of H.
      longicornis, the number of female adults, male adults, nymphs, and larvae were
      53, 11, 240, and 446, respectively. Ticks were grouped into 63 pools according to
      the collection site, species, and developmental stage, and assayed for SFTS
      virus. None of the pools of ticks were found to be positive for SFTS virus gene. 

PMID- 24850971
TI  - Larval chigger mites collected from small mammals in 3 provinces, Korea.
AB  - A total of 9,281 larval chigger mites were collected from small mammals captured
      at Hwaseong-gun, Gyeonggi-do (Province) (2,754 mites from 30 small mammals), Asan
      city, Chungcheongnam-do (3,358 mites from 48 mammals), and Jangseong-gun,
      Jeollanam-do (3,169 for 62 mammals) from April-November 2009 in the Republic of
      Korea (= Korea) and were identified to species. Leptotrombidium pallidum was the
      predominant species in Hwaseong (95.8%) and Asan (61.2%), while Leptotrombidium
      scutellare was the predominant species collected from Jangseong (80.1%). Overall,
      larval chigger mite indices decreased from April (27.3) to June (4.9), then
      increased in September (95.2) and to a high level in November (169.3). These data
      suggest that L. pallidum and L. scutellare are the primary vectors of scrub
      typhus throughout their range in Korea. While other species of larval chigger
      mites were also collected with some implications in the transmission of Orientia
      tsutsugamushi, they only accounted for 11.2% of all larval chigger mites
      collected from small mammals. 

PMID- 24850972
TI  - Stress relaxation study of fillers for directly compressed tablets.
AB  - It is possible to assess viscoelastic properties of materials by means of the
      stress relaxation test. This method records the decrease in pressing power in a
      tablet at its constant height. The cited method was used to evaluate the time
      dependent deformation for six various materials: microcrystalline cellulose,
      cellulose powder, hydroxypropyl methylcellulose, mannitol, lactose monohydrate,
      and hydrogen phosphate monohydrate. The decrease in pressing powering of a tablet
      during a 180 s period was described mathematically by the parameters of three
      exponential equations, where the whole course of the stress relaxation is divided
      into three individual processes (instant elastic deformation, retarded elastic
      deformation and permanent plastic deformation). Three values of the moduli of
      plasticity and elasticity were calculated for each compound. The values of
      elastic parameters ATi have a strong relationship with bulk density. The plastic
      parameters PTi represent particle tendency to form bonds. The values of
      plasticity in the third process PT3 ranged from 400 to 600 MPas. Mannitol had
      higher plasticity and lactose monohydrate on the contrary reduced plasticity. A
      linear relation exists between AT3 and PT3 for the third process. No similar
      interpretation of moduli calculated on the basis of three exponential equations
      has been realized yet.

PMID- 24850973
TI  - The Effects of World War II on Economic and Health Outcomes across Europe.
AB  - We investigate long-run effects of World War II on socio-economic status and
      health of older individuals in Europe. We analyze data from SHARELIFE, a
      retrospective survey conducted as part of SHARE in Europe in 2009. SHARELIFE
      provides detailed data on events in childhood during and after the war for over
      20,000 individuals in 13 European countries. We construct several measures of war
      exposure-experience of dispossession, persecution, combat in local areas, and
      hunger periods. Exposure to war and more importantly to individual-level shocks
      caused by the war significantly predicts economic and health outcomes at older
      ages.

PMID- 24850974
TI  - Expectations as a key to understanding actor strategies in the field of fuel cell
      and hydrogen vehicles.
AB  - Due to its environmental impact, the mobility system is increasingly under
      pressure. The challenges to cope with climate change, air quality, depleting
      fossil resources imply the need for a transition of the current mobility system
      towards a more sustainable one. Expectations and visions have been identified as
      crucial in the guidance of such transitions, and more specifically of actor
      strategies. Still, it remained unclear why the actors involved in transition
      activities appear to change their strategies frequently and suddenly. The
      empirical analysis of the expectations and strategies of three actors in the
      field of hydrogen and fuel cell technology indicates that changing actor
      strategies can be explained by rather volatile expectations related to different
      levels. Our case studies of the strategies of two large car manufacturers and the
      German government demonstrate that the car manufacturers refer strongly to
      expectations about the future regime, while expectations related to the socio
      technical landscape level appear to be crucial for the strategy of the German
      government.

PMID- 24850975
TI  - VARIABLE SELECTION IN LINEAR MIXED EFFECTS MODELS.
AB  - This paper is concerned with the selection and estimation of fixed and random
      effects in linear mixed effects models. We propose a class of nonconcave
      penalized profile likelihood methods for selecting and estimating important fixed
      effects. To overcome the difficulty of unknown covariance matrix of random
      effects, we propose to use a proxy matrix in the penalized profile likelihood. We
      establish conditions on the choice of the proxy matrix and show that the proposed
      procedure enjoys the model selection consistency where the number of fixed
      effects is allowed to grow exponentially with the sample size. We further propose
      a group variable selection strategy to simultaneously select and estimate
      important random effects, where the unknown covariance matrix of random effects
      is replaced with a proxy matrix. We prove that, with the proxy matrix
      appropriately chosen, the proposed procedure can identify all true random effects
      with asymptotic probability one, where the dimension of random effects vector is
      allowed to increase exponentially with the sample size. Monte Carlo simulation
      studies are conducted to examine the finite-sample performance of the proposed
      procedures. We further illustrate the proposed procedures via a real data
      example.

PMID- 24850976
TI  - Computed 3D visualisation of an extinct cephalopod using computer tomographs.
AB  - The first 3D visualisation of a heteromorph cephalopod species from the Southern
      Alps (Dolomites, northern Italy) is presented. Computed tomography,
      palaeontological data and 3D reconstructions were included in the production of a
      movie, which shows a life reconstruction of the extinct organism. This detailed
      reconstruction is according to the current knowledge of the shape and mode of
      life as well as habitat of this animal. The results are based on the most
      complete shell known thus far of the genus Dissimilites. Object-based combined
      analyses from computed tomography and various computed 3D facility programmes
      help to understand morphological details as well as their ontogentical changes in
      fossil material. In this study, an additional goal was to show changes in
      locomotion during different ontogenetic phases of such fossil, marine shell
      bearing animals (ammonoids). Hence, the presented models and tools can serve as
      starting points for discussions on morphology and locomotion of extinct
      cephalopods in general, and of the genus Dissimilites in particular. The
      heteromorph ammonoid genus Dissimilites is interpreted here as an active swimmer
      of the Tethyan Ocean. This study portrays non-destructive methods of 3D
      visualisation applied on palaeontological material, starting with computed
      tomography resulting in animated, high-quality video clips. The here presented 3D
      geometrical models and animation, which are based on palaeontological material,
      demonstrate the wide range of applications, analytical techniques and also
      outline possible limitations of 3D models in earth sciences and palaeontology.
      The realistic 3D models and motion pictures can easily be shared amongst
      palaeontologists. Data, images and short clips can be discussed online and, if
      necessary, adapted in morphological details and motion-style to better represent
      the cephalopod animal.

PMID- 24850977
TI  - The Influence of Kinship on Familiar Natal Migrant Rhesus Macaques (Macaca
      mulatta).
AB  - In most primate species, females remain in the natal group with kin while males
      disperse away from kin around the time of puberty. Philopatric females bias their
      social behavior toward familiar maternal and paternal kin in several species, but
      little is known about kin bias in the dispersing sex. Male dispersal is likely to
      be costly because males encounter an increased risk of predation and death, which
      might be reduced by dispersing together with kin and/or familiar males
      (individuals that were born and grew up in same natal group) or into a group
      containing kin and/or familiar males. Here we studied the influence of kinship on
      familiar natal migrant rhesus macaques (Macaca mulatta) on Cayo Santiago, Puerto
      Rico, by combining demographic, behavioral, and genetic data. Our data suggest
      that kinship influences spatial proximity between recent natal immigrants and
      males familiar to them. Immigrants were significantly nearer to more closely
      related familiar males than to more distantly related individuals. Within a
      familiar subgroup, natal migrants were significantly closer to maternal kin,
      followed by paternal kin, then non-kin, and finally to males related via both the
      maternal and paternal line. Spatial proximity between natal immigrants and
      familiar males did not decrease over time in the new group, suggesting that there
      is no decline in associations between these individuals within the first months
      of immigration. Overall, our results might indicate that kinship is important for
      the dispersing sex, at least during natal dispersal when kin are still available.

PMID- 24850978
TI  - Authoritarian Parenting and Asian Adolescent School Performance: Insights from
      the US and Taiwan.
AB  - Our study re-examines the relationship between parenting and school performance
      among Asian students. We use two sources of data: wave I of the Adolescent Health
      Longitudinal Survey (Add Health), and waves I and II of the Taiwan Educational
      Panel Survey (TEPS). Analysis using Add Health reveals that the Asian
      American/European-American difference in the parenting-school performance
      relationship is due largely to differential sample sizes. When we select a random
      sample of European-American students comparable to the sample size of Asian
      American students, authoritarian parenting also shows no effect for European
      American students. Furthermore, analysis of TEPS shows that authoritarian
      parenting is negatively associated with children's school achievement, while
      authoritative parenting is positively associated. This result for Taiwanese
      Chinese students is similar to previous results for European-American students in
      the US.

PMID- 24850979
TI  - 60 MHz 1H NMR spectroscopy for the analysis of edible oils.
AB  - We report the first results from a new 60 MHz 1H nuclear magnetic resonance (NMR)
      bench-top spectrometer, Pulsar, in a study simulating the adulteration of olive
      oil with hazelnut oil. There were qualitative differences between spectra from
      the two oil types. A single internal ratio of two isolated groups of peaks could
      detect hazelnut oil in olive oil at the level of ~13%w/w, whereas a whole
      spectrum chemometric approach brought the limit of detection down to 11.2%w/w for
      a set of independent test samples. The Pulsar's performance was compared to that
      of Fourier transform infrared (FTIR) spectroscopy. The Pulsar delivered
      comparable sensitivity and improved specificity, making it a superior screening
      tool. We also mapped NMR onto FTIR spectra using a correlation-matrix approach.
      Interpretation of this heat-map combined with the established annotations of the
      NMR spectra suggested a hitherto undocumented feature in the IR spectrum at ~1130
      cm-1, attributable to a double-bond vibration.

PMID- 24850980
TI  - Treatment of hepatitis C virus infection and associated vascular complications: a
      literature review.
AB  - Interferon (IFN)-based therapy, the cornerstone for treatment of hepatitis C
      virus (HCV) infection, is generally considered to be the single most effective
      treatment strategy for this infection. Although most adverse effects of IFN
      therapy respond very well to the cessation of this drug, there are reports of
      serious irreversible adverse effects. This review article evaluates the adverse
      effects of IFN therapy in HCV-infected patients. We have undertaken an extensive
      search for articles regarding IFN and pegylated-IFN (PEG-IFN) therapy and their
      vascular complications using multiple sources that include PubMed, publishers'
      websites, and Google Scholar. The prevalence of ocular disorders in the early
      period (first 8 weeks) after IFN administration was high with over half of the
      patients experiencing these adverse effects. Several authors strongly propose
      screening programs for retinopathy in the early period after IFN administration.
      Pulmonary hypertension due to IFN therapy is a serious side effect due to its
      irreversible nature in most patients. Patients who develop signs of acute abdomen
      up to months after IFN administration should be rapidly assessed for potential
      adverse effects of IFN. The literature suggests a broad spectrum of vascular
      injuries to different organs in humans as adverse effects of IFN therapy in HCV
      infected patients. 

PMID- 24850981
TI  - The Effect of Intraoperative Restricted Normal Saline during Orthotopic Liver
      Transplantation on Amount of Administered Sodium Bicarbonate.
AB  - BACKGROUND: Severe metabolic acidosis occurs during orthotopic liver
      transplantation (OLT) particularly during the anhepatic phase. Although NaHCO3 is
      considered as the current standard therapy, there are numerous adverse effects.
      The aim of this study was to determine whether the restricted use of normal
      saline during anesthesia could reduce the need for NaHCO3. METHODS: In this study
      we enrolled 75 patients with end-stage liver disease who underwent OLT from
      February 2010 until September 2010 at the Shiraz Organ Transplantation Center.
      Fluid management of two different transplant anesthetics were compared. The
      effect of restricted normal saline fluid was compared with non-restricted normal
      saline fluid on hemodynamic and acid-base parameters at three times during OLT:
      after the skin incision (T1), 15 min before reperfusion (T2), and 5 min after
      reperfusion (T3). RESULTS: There were no significant differences in demographic
      characteristics of the donors and recipients (P>0.05). In the restricted normal
      saline group there was significantly lower central venous pressure (CVP) than in
      the non-restricted normal saline group (P=0.002). No significant differences were
      noted in the other hemodynamic parameters between the two groups (P>0.05). In the
      non-restricted normal saline group arterial blood pH (P=0.01) and HCO3 (P=0.0001)
      were significantly less than the restricted normal saline group. The NaHCO3
      requirement before reperfusion was significantly more than with the restricted
      normal saline group (P=0.001). CONCLUSION: Restricted normal saline
      administration during OLT reduced the severity of metabolic acidosis and the need
      for NaHCO3 during the anhepatic phase. TRIAL REGISTRATION NUMBER:
      IRCT2013110711662N5.

PMID- 24850982
TI  - Risk factors of dystocia in nulliparous women.
AB  - BACKGROUND: Detection of women at risk for dystocia will allow physicians to make
      preparations and treatment decisions that can minimize maternal and neonatal
      morbidity. We aimed to determine the risk factors for dystocia in nulliparous
      women. METHODS: This case series enrolled 447 nulliparous women who presented
      with a single pregnancy in the vertex presentation and gestational age of 38-42
      weeks. Maternal anthropometric measurements were obtained upon admission. We
      defined dystocia as a cesarean section or vacuum delivery for abnormal
      progression of labor as evidenced by the presence of effective uterine
      contractions, cervical dilation of less than 1 cm/h in the active phase for 2 h,
      duration of the second stage beyond 2 h, or fetal head descent less than 1 cm/h.
      Data were analyzed by SPSS software version 11.5. Kruskal-Wallis, logistic
      regression, chi-square, Student's t test and the Mann-Whitney tests were used as
      appropriated. RESULTS: The state anxiety score (OR=10.58, CI: 1.97-56.0),
      posterior head position (OR=9.53, CI: 4.68-19.36), fetal head swelling in the
      second stage of labor (OR=6.85, CI: 2.60-18.01), transverse diagonal of Michaelis
      sacral <=9.6 cm (OR=6.19, CI: 2.49-15.40), and height to fundal ratio <4.7
      (OR=2.68, CI: 1.09-10.60) were significant risk factors for dystocia. CONCLUSION:
      Critical care during labor and delivery in women who have a height to fundal
      height ratio of <4.7 or transverse diagonal of Michaelis sacral <=9.6 cm, an
      anxiety score greater than moderate, and posterior head position or fetal head
      swelling during the second phase could play an effective and important role in
      preventing dystocia.

PMID- 24850983
TI  - Morphine Reduces Expression of TRPV1 Receptors in the Amygdala but not in the
      Hippocampus of Male Rats.
AB  - BACKGROUND: Chronic use of opioids usually results in physical dependence. The
      underlying mechanisms for this dependence are still being evaluated. Transient
      receptor potential vanilloid type 1 (TRPV1) are important receptors of pain
      perception. Their role during opioid dependence has not been studied well. The
      aim of this study was to evaluate the effect of morphine-dependence on the
      expression of TRPV1 receptors in the amygdala and CA1 region of the hippocampus.
      METHODS: This study used four groups of rats. Two groups of rats (morphine and
      morphine+naloxone) received morphine based on the following protocol: 10 mg/kg
      (twice daily, 3 days) followed by 20, 30, 40 and 50 mg/kg (twice daily),
      respectively, for 4 consecutive days. Another group received vehicle (1 ml/kg)
      instead of morphine given using the same schedule. The morphine+naloxone group of
      rats additionally received naloxone (5 mg/kg) at the end of the protocol. The
      control group rats received no injections or intervention. The amygdala and CA1
      regions of the morphine, saline-treated and intact animals were isolated and
      prepared for real-time PCR analysis. RESULTS: Administration of naloxone induced
      withdrawal signs in morphine-treated animals. The results showed a significant
      decrease in TRPV1 gene expression in the amygdala (P<0.05) but not the CA1 region
      of morphine dependent rats. CONCLUSION: TRPV1 receptors may be involved in
      morphine-induced dependence.

PMID- 24850984
TI  - The Study of DNA Methyltransferase-3B Promoter Variant Genotype among Iranian
      Sporadic Breast Cancer Patients.
AB  - BACKGROUND: DNA methyltransferase-3B (DNMT3B) is an important enzyme responsible
      for maintaining the DNA methylation pattern in eukaryotic cells. In this study we
      have investigated the correlation between the 46359C->T polymorphism in the
      DNMT3B gene and the risk of breast cancer incidence among sporadic breast cancer
      patients in Fars Province, Southern Iran. METHODS: In this case-control study,
      100 breast cancer patients and 138 healthy control subjects were genotyped for
      the DNMT3B gene by the polymerase chain reaction-restriction fragment length
      polymorphism method. RESULTS: The genotype frequency in the case (CC 27%, CT 47%,
      TT 26%) group significantly (P=0.008) differed from the control (CC 19.56%, CT
      67.3%, TT 13%) group. We observed a decreased association between the CT genotype
      and lymph node involvement in breast cancer patients. Our results have shown that
      in comparison to the homozygous CC genotype carriers the DNMT3B-CT genotype has a
      significantly lower risk for breast cancer (OR=0.515, 95% CI=0.267-0.994,
      P=0.048). CONCLUSION: Our case-control study showed that the CT genotype was
      significantly associated with decreased breast cancer risk. Consistent with these
      results, a significant decrease of CT genotype among lymph node positive breast
      cancer patients was observed. However, a larger study population with more
      clinical data is needed to confirm these results.

PMID- 24850985
TI  - Sustained Hypoxic Pulmonary Vasoconstriction in the Isolated Perfused Rat Lung:
      Effect of alpha1-adrenergic Receptor Agonist.
AB  - BACKGROUND: Alveolar hypoxia induces monophasic pulmonary vasoconstriction in
      vivo, biphasic vasoconstriction in the isolated pulmonary artery, and
      controversial responses in the isolated perfused lung. Pulmonary vascular
      responses to sustained alveolar hypoxia have not been addressed in the isolated
      perfused rat lung. In this study, we investigated the effect of sustained hypoxic
      ventilation on pulmonary artery pressure in the present of phenylephrine, an
      alpha1-receptor agonist, under the above condition. METHODS: We performed this
      study in the isolated perfused rat lung. After preparation, the lungs were
      divided randomly into five groups of normoxic-normocapnia, hypoxic-normocapnia,
      phenylephrine pre- or post-treated hypoxic-normocapnia and phenylephrine pre
      treated normoxic-normocapnia. Pulmonary hemodynamic, airway pressure and lung
      weight were measured during 60 min of the experiment for each group. RESULTS: In
      the phenylephrine-pre-treated hypoxic-normocapnia group we observed a gradual
      increase in pulmonary artery pressure which approximated the results seen in the
      phenylephrine-pre-treated normoxic-normocapnia group. In contrast, in the
      phenylephrine-post-treated hypoxic-normcapnic group, pulmonary artery pressure
      did not change during the first 3 min of hypoxic-normocapnia. However at 1.5 min
      after administration of phenylephrine, this pressure began to increase sharply
      and continued until the end of the experiment. This response was biphasic (0-10
      min: acute phase, 10-60 min: sustained phase) with significantly higher pulmonary
      artery pressure compared to the other groups. CONCLUSION: This study, for the
      first time, showed biphasic hypoxic pulmonary vasoconstriction in the isolated
      perfused rat lung with the sole administration of phenylephrine after but not
      before hypoxic gas ventilation. This finding suggested a facilitative role of
      alveolar hypoxia on pulmonary vasoconstriction induced by an alpha1-receptor
      agonist.

PMID- 24850986
TI  - Optimization of RNA extraction from rat pancreatic tissue.
AB  - BACKGROUND: Optimized RNA extraction from tissues and cell lines consists of four
      main stages regardless of the method of extraction: 1) homogenizing, 2) effective
      denaturation of proteins from RNA, 3) inactivation of ribonuclease, and 4)
      removal of any DNA, protein, and carbohydrate contamination. Isolation of
      undamaged intact RNA is challenging when the related tissue contains high levels
      of RNase. Various technical difficulties occur during extraction of RNA from
      pancreatic tissue due to spontaneous autolysis. Since standard routine protocols
      yield unacceptable results in pancrease, we have designed a simple method for RNA
      extraction by comparing different protocols. METHODS: We obtained 20-30 mg
      pancreatic tissues in less than 2 min from 30 rats. Several methods were
      performed to extract RNA from pancreatic tissue and evaluate its integrity. All
      methods were performed three times to obtain reproducible results. RESULTS:
      Immersing pancreatic tissue in RNA-later for 24 h at -80oC yielded high quality
      RNA by using the TriPure reagent which was comparable to the commercial RNeasy
      Micro Kit. The quality of RNA was evaluated by spectrophotometer, electrophoresis
      and RT-PCR. We separated intact 28S and 18S ribosomal RNA (rRNA) when our
      procedure was compared with the RNeasy Micro Kit. Finally, full length of the
      actin gene was amplified by RT-PCR. CONCLUSION: We designed a simple, fast, cost
      effective method for complete RNA extraction from the least amount of
      quantitatively intact pancreatic tissue.

PMID- 24850987
TI  - Evaluation of thymic changes after median sternotomy in children.
AB  - In patients who undergo median sternotomy to treat congenital heart diseases, a
      thymectomy is performed to yield better access to the cardiac system. In this
      study we have used MRI to evaluate the changes in size, shape and location of the
      thymus after midsternatomy. This case-control study was performed during 2011
      2012 in Shiraz, Iran. Eligible participants between 5-17 years of age were
      divided into case and control groups (n=13 per group). Each participant underwent
      a median sternotomy at least one year prior to study entry. Participants were
      initially examined by a cardiologist and then referred for MRI. A radiologist
      examined all MRI images. The thymus was observed in all control group patients
      and in only 7 (53.8%) patients in the case group. There was a significant
      relationship noted in terms of mean age in the group whose thymus was visible and
      the group in which the thymus was not visible. We have observed no significant
      difference in thymic visibility between these two groups based on the mean age at
      midsternatomy. In pediatric patients undergoing cardiac surgery the possibility
      of remaining or regenerated thymic tissues may be evaluated by MRI. The remaining
      portion of the thymus may have any shape, size or location. Therefore, it can be
      misinterpreted as a mass if a patient's previous surgical history and age at the
      time of surgery are not taken into consideration. 

PMID- 24850988
TI  - Medical students' knowledge of indications for imaging modalities and cost
      analysis of incorrect requests, shiraz, iran 2011-2012.
AB  - Medical imaging has a remarkable role in the practice of clinical medicine. This
      study intends to evaluate the knowledge of indications of five common medical
      imaging modalities and estimation of the imposed cost of their non-indicated
      requests among medical students who attend Shiraz University of Medical Sciences,
      Shiraz, Iran. We conducted across-sectional survey using a self-administered
      questionnaire to assess the knowledge of indications of a number of medical
      imaging modalities among 270 medical students during their externship or
      internship periods. Knowledge scoring was performed according to a descriptive
      international grade conversion (fail to excellent) using Iranian academic grading
      (0 to 20). In addition, we estimated the cost for incorrect selection of those
      modalities according to public and private tariffs in US dollars. The
      participation and response rate was 200/270 (74%). The mean knowledge score was
      fair for all modalities. Similar scores were excellent for X-ray, acceptable for
      Doppler ultrasonography, and fair for ultrasonography, CT scan and MRI. The total
      cost for non-indicated requests of those modalities equaled $104303 (public
      tariff) and $205581 (private tariff). Medical students at Shiraz University of
      Medical Sciences lacked favorable knowledge about indications for common medical
      imaging modalities. The results of this study have shown a significant cost for
      non-indicated requests of medical imaging. Of note, the present radiology
      curriculum is in need of a major revision with regards to evidence-based
      radiology and health economy concerns. 

PMID- 24850989
TI  - Non-diethylstilbestrol-associated primary clear cell carcinoma of the vagina: two
      case reports with immunohistochemical studies and literature review.
AB  - Primary clear cell adenocarcinomas most commonly involve the genitourinary
      system, including the vagina. Previously, primary clear cell adenocarcinomas of
      the vagina have been discussed within the context of prenatal exposure to
      diethylstilbestrol. Due to its widely proven role in the development of this
      carcinoma, administration of diethylstilbestrol is prohibited. We present two
      cases of non-diethylstilbestrol-associated primary clear cell adenocarcinoma of
      the vagina from the archives of the Anatomical Pathology Department at King
      Abdulaziz University in order to improve our understanding of its biological
      behavior. Our findings suggest that primary clear cell adenocarcinoma of the
      vagina may be unrelated to diethylstilbestrol exposure and that non
      diethylstilbestrol-associated primary clear cell adenocarcinoma of the vagina,
      when present at a younger age, may have a worse prognosis. 

PMID- 24850990
TI  - Nevus lipomatosus cutaneous superficialis: a rare case report.
AB  - Nevus lipomatosus cutaneous superficialis is a rare idiopathic hamartomatous
      anomaly of the skin characterized by the presence of clusters of mature fat cells
      among the collagen bundles of the dermis. The classic, or solitary type, presents
      with asymptomatic soft, skin-colored to yellow papules or nodules. We report the
      case of a 12-year-old boy with congenital, classical nevus lipomatosus cutaneous
      superficialis that started as a single painless nodule. Over time, the nodule
      developed into lesions that presented as skin-colored, well-defined, soft sessile
      growths with a cerebriform surface centered by comedo-like plugs that increased
      in size and spread over a large area (approximately 12*4 cm) over the right
      gluteal region. We report this case as it is an uncommon condition with the
      intent to highlight its clinical and histopathological features, and differential
      diagnosis. 

PMID- 24850991
TI  - A new brace for maintaining the neck in a suitable position following tracheal
      reconstruction.
AB  - Segmental resection and end-to-end anastomosis is the treatment of choice for
      patients suffering from tracheal stenosis for whom conservative management is not
      planned. A complication of this procedure is tension-induced anastomotic failure.
      To prevent this complication, maintaining the neck in full flexion by means of a
      suture between the chin and upper chest is a traditional approach. We have
      designed a new brace (Shiraz brace) that securely supports the neck in this
      position and decreases the bothersome use of the suture alone. 

PMID- 24850993
TI  - The authors' reply.

PMID- 24850992
TI  - What about Memory, Consciousness, Recall, and Awareness in Anesthesia?

PMID- 24850994
TI  - Voting at 16: Turnout and the quality of vote choice.
AB  - Critics of giving citizens under 18 the right to vote argue that such teenagers
      lack the ability and motivation to participate effectively in elections. If this
      argument is true, lowering the voting age would have negative consequences for
      the quality of democracy. We test the argument using survey data from Austria,
      the only European country with a voting age of 16 in nation-wide elections. While
      the turnout levels of young people under 18 are relatively low, their failure to
      vote cannot be explained by a lower ability or motivation to participate. In
      addition, the quality of these citizens' choices is similar to that of older
      voters, so they do cast votes in ways that enable their interests to be
      represented equally well. These results are encouraging for supporters of a lower
      voting age.

PMID- 24850995
TI  - Available evidence does not support serosorting as an HIV risk reduction
      strategy: author's reply.

PMID- 24850996
TI  - Girls, girls, girls: Gender composition and female school choice.
AB  - Gender segregation in employment may be explained by women's reluctance to choose
      technical occupations. However, the foundations for career choices are laid much
      earlier. Educational experts claim that female students are doing better in math
      and science and are more likely to choose these subjects if they are in single
      sex classes. One possible explanation is that coeducational settings reinforce
      gender stereotypes. In this paper, we identify the causal impact of the gender
      composition in coeducational classes on the choice of school type for female
      students. Using natural variation in the gender composition of adjacent cohorts
      within schools, we show that girls are less likely to choose a traditionally
      female dominated school type and more likely to choose a male dominated school
      type at the age of 14 if they were exposed to a higher share of girls in previous
      grades.

PMID- 24850997
TI  - Of credence and credibility: A year gone by.

PMID- 24850998
TI  - Presidential address.

PMID- 24850999
TI  - Measuring brain activity.

PMID- 24851000
TI  - Functional MRI: Genesis, State of the art and the Sequel.

PMID- 24851001
TI  - fMRI paradigm designing and post-processing tools.
AB  - In this article, we first review some aspects of functional magnetic resonance
      imaging (fMRI) paradigm designing for major cognitive functions by using stimulus
      delivery systems like Cogent, E-Prime, Presentation, etc., along with their
      technical aspects. We also review the stimulus presentation possibilities (block,
      event-related) for visual or auditory paradigms and their advantage in both
      clinical and research setting. The second part mainly focus on various fMRI data
      post-processing tools such as Statistical Parametric Mapping (SPM) and Brain
      Voyager, and discuss the particulars of various preprocessing steps involved
      (realignment, co-registration, normalization, smoothing) in these software and
      also the statistical analysis principles of General Linear Modeling for final
      interpretation of a functional activation result. 

PMID- 24851002
TI  - Clinical utility of BOLD fMRI in preoperative work-up of epilepsy.
AB  - Surgical techniques have emerged as a viable therapeutic option in patients with
      drug refractory epilepsy. Pre-surgical evaluation of epilepsy requires a
      comprehensive, multiparametric, and multimodal approach for precise localization
      of the epileptogenic focus. Various non-invasive techniques are available at the
      disposal of the treating physician to detect the epileptogenic focus, which
      include electroencephalography (EEG), video-EEG, magnetic resonance imaging
      (MRI), functional MRI including blood oxygen level dependent (BOLD) techniques,
      single photon emission tomography (SPECT), and (18)F-fluorodeoxyglucose (FDG)
      positron emission tomography (PET). Currently, non-invasive high-resolution MR
      imaging techniques play pivotal roles in the preoperative detection of the
      seizure focus, and represent the foundation for successful epilepsy surgery. BOLD
      functional magnetic resonance imaging (fMRI) maps allow for precise localization
      of the eloquent cortex in relation to the seizure focus. This review article
      focuses on the clinical utility of BOLD (fMRI) in the pre-surgical work-up of
      epilepsy patients. 

PMID- 24851003
TI  - fMRI for mapping language networks in neurosurgical cases.
AB  - Evaluating language has been a long-standing application in functional magnetic
      resonance imaging (fMRI) studies, both in research and clinical circumstances,
      and still provides challenges. Localization of eloquent areas is important in
      neurosurgical cases, so that there is least possible damage to these areas during
      surgery, maintaining their function postoperatively, therefore providing good
      quality of life to the patient. Preoperative fMRI study is a non-invasive tool to
      localize the eloquent areas, including language, with other traditional methods
      generally used being invasive and at times perilous. In this article, we describe
      methods and various paradigms to study the language areas, in clinical
      neurosurgical cases, along with illustrations of cases from our institute. 

PMID- 24851004
TI  - Reading in Devanagari: Insights from functional neuroimaging.
AB  - OBJECTIVES: The current study used functional MRI (fMRI) to obtain a
      comprehensive understanding of the neural network underlying visual word
      recognition in Hindi/Devanagari, an alphasyllabic - partly alphabetic and partly
      syllabic Indian writing system on which little research has hitherto been carried
      out. MATERIALS AND METHODS: Sixteen (5F, 11M) neurologically healthy, native
      Hindi/Devanagari readers aged 21 to 50 named aloud 240 Devanagari words which
      were either visually linear - had no diacritics or consonant ligatures above or
      below central plane of text, e.g. ??, ????, or nonlinear - had at least one
      diacritic and/or ligature, e.g. ???, ????, and which further included 120 words
      each of high and low frequency. Words were presented in alternating high and low
      frequency blocks of 10 words each at 2s/word in a block design, with linear and
      nonlinear words in separate runs. Word reading accuracy was manually coded, while
      fMRI images were acquired on a 3T scanner with an 8-channel head-coil, using a
      T2*-weighted EPI sequence (TR/TE = 2s/35ms). RESULTS: After ensuring high word
      naming accuracy (M = 97.6%, SD = 2.3), fMRI data analyses (at FDR P < 0.005)
      revealed that reading Devanagari words elicited robust activations in bilateral
      occipito-temporal, inferior frontal and precentral regions as well as both
      cerebellar hemispheres. Other common areas of activation included left inferior
      parietal and right superior temporal cortices. Primary differences seen between
      nonlinear and linear word reading networks were in the right temporal areas and
      cerebellum. CONCLUSION: Distinct from alphabetic scripts, which are linear in
      their spatial organization, and recruit a primarily left-lateralized network for
      word reading, our results revealed a bilateral reading network for Devanagari. We
      attribute the additional activations in Devanagari to increased visual processing
      demands arising from the complex visuospatial arrangement of symbols in this
      ancient script.

PMID- 24851005
TI  - Mapping of cognitive functions in chronic intractable epilepsy: Role of fMRI.
AB  - BACKGROUND: Functional magnetic resonance imaging (fMRI), a non-invasive
      technique with high spatial resolution and blood oxygen level dependent (BOLD)
      contrast, has been applied to localize and map cognitive functions in the
      clinical condition of chronic intractable epilepsy. PURPOSE: fMRI was used to map
      the language and memory network in patients of chronic intractable epilepsy pre-
      and post-surgery. MATERIALS AND METHODS: After obtaining approval from the
      institutional ethics committee, six patients with intractable epilepsy with an
      equal number of age-matched controls were recruited in the study. A 1.5 T MR
      scanner with 12-channel head coil, integrated with audio-visual fMRI accessories
      was used. Echo planar imaging sequence was used for BOLD studies. There were two
      sessions in TLE (pre- and post-surgery). RESULTS: In TLE patients, BOLD
      activation increased post-surgery in comparison of pre-surgery in inferior
      frontal gyrus (IFG), middle frontal gyrus (MFG), and superior temporal gyrus
      (STG), during semantic lexical, judgment, comprehension, and semantic memory
      tasks. CONCLUSION: Functional MRI is useful to study the basic concepts related
      to language and memory lateralization in TLE and guide surgeons for preservation
      of important brain areas during ATLR. This will help in understanding future
      directions for the diagnosis and treatment of such disease.

PMID- 24851006
TI  - Cerebral encephalopathy with extrapontine myelinolysis in a case of postpartum
      hypernatremia.
AB  - Extrapontine myelinolysis, a fairly common metabolic disorder, is associated with
      neurological complications. Central pontine and extrapontine myelinolysis are
      commonly recognized with rapid correction of sodium. Myelinolysis, however, has
      rarely been described with hypernatremia. We report a rare case of post-partum
      hypernatremic encephalopathy associated with serum sodium levels as high as 200
      mEq/l on presentation. Although the serum sodium levels were brought down
      gradually, subsequent imaging showed progression of demyelination and
      deterioration of the neurological status. 

PMID- 24851007
TI  - Bilateral asymmetrical duplicated origin of vertebral arteries: Multidetector row
      CT angiographic study.
AB  - Bilateral duplicated origin of V-1 segment of vertebral arteries is an extremely
      rare vascular variant and only two such cases have been reported so far. Presence
      of this vascular abnormality was observed incidentally in a 36-year-old male
      patient, with a complaint of dizziness, evaluated by multidetector row computed
      tomography (CT) angiography. Two limbs of the right vertebral artery arose from
      the right subclavian artery and fused to form a single vessel at the interval
      between fourth and fifth cervical vertebrae, which entered the foramen
      transversarium of fourth cervical vertebra. On the left side, the medial limb
      originated directly from the arch of aorta and the lateral limb from the left
      subclavian artery, and both united at the interval between fifth and sixth
      cervical vertebrae to form a single vessel which entered the foramen
      transversarium of fifth cervical vertebra. No other cerebrovascular pathology
      like aneurysm, fenestration, dissection, and stenosis was detected, which could
      be correlated with the symptoms of the patient. This rare congenital vascular
      anomaly has diagnostic and therapeutic implications in any intervention involving
      the vertebral artery. 

PMID- 24851008
TI  - Variations in superior thyroid artery: A selective angiographic study.
AB  - AIM: To investigate variations in superior thyroid artery (STA) based on digital
      subtraction angiography (DSA). MATERIALS AND METHODS: Twenty five angiography
      studies of 15 pts performed between June 2010 and December 2012 were
      retrospectively evaluated. These patients underwent DSA of the head and neck
      region as a part of their superselective neoadjuvant intra-arterial chemotherapy
      protocol for treatment of laryngeal and hypopharyngeal cancers. Depending upon
      the location of the tumor, unilateral or bilateral arteriograms of common carotid
      artery (CCA), external carotid artery (ECA), and STA were performed. Arteriograms
      were evaluated for the site of origin and branching pattern of STA. STA anatomy
      was ascribed to one of the three branching patterns. RESULTS: A total of 25
      angiograms were evaluated, including 14 right and 11 left. On the right side, STA
      was noted to arise from ECA in 10 (71.5%), bifurcation of CCA in 3 (21.5%), and
      CCA in 1 (7%) patient. Left STA was seen to arise from ECA in 8 (72.5%),
      bifurcation of CCA in 2 (18.5%), and internal carotid artery (ICA) in 1 (9%)
      patient. Type III branching pattern (non-bifurcation, non-trifurcation) was found
      to be the most frequent (52%). Infrahyoid branch was found to be the most
      consistent in terms of its origin from STA. CONCLUSIONS: Origin of STA is
      predictable, arising from ECA in more than 70% cases. Branching pattern of STA,
      following origin from ECA, is, however, highly variable. Knowledge concerning the
      origin and branching pattern of STA is essential in enhancing precision and
      decreasing morbidity related to the surgical and interventional radiological head
      and neck procedures.

PMID- 24851009
TI  - Missed intranasal wooden foreign bodies on computed tomography.
AB  - We report a case of post traumatic impacted intranasal wooden foreign body in a
      16 year old boy, which was undetected on Computed Tomography in the acute stage.
      Intranasal wooden foreign body may be missed on CT in the acute stage because of
      apparent air attenuation of the foreign body and lack of contrast with the
      surrounding intranasal air. Radiologists need to be aware of the CT imaging
      appearances of wood in various stages for early detection and management. 

PMID- 24851010
TI  - Pseudomalignant myositis ossificans involving multiple masticatory muscles:
      Imaging evaluation.
AB  - Myositis ossificans is a rare cause of trismus. We present a case of
      pseudomalignant myositis ossificans involving medial pterygoid, lateral
      pterygoid, and temporalis muscles. Patient presented with gross limitation in
      mouth opening. There was no history of trauma. Computed tomography (CT) images
      revealed a bone density mass located in the region of medial and lateral
      pterygoid muscles on the right and temporalis muscle on the left. Magnetic
      resonance imaging (MRI) showed similar findings. Radiological diagnosis was
      pseudomalignant myositis ossificans. The masses were resected and histopathologic
      examination confirmed the above diagnosis. This report describes the
      characteristic CT and MRI features. The unique feature of this case is the
      absence of history of trauma with involvement of multiple masticatory muscles,
      which, to the best of our knowledge, has not been reported before. 

PMID- 24851011
TI  - Utility of C-arm CT in overcoming challenges in patients undergoing Transarterial
      chemoembolization for hepatocellular carcinoma.
AB  - Transarterial chemoembolization (TACE) is the well-known treatment for
      hepatocellular carcinoma. Multiple digital subtraction angiography (DSA)
      acquisitions in different projections are required to identify difficult arterial
      feeders. Moreover, the tell-tale tumor blush can be obscured by proximity to lung
      base, small size of lesion, and breathing artifacts. C-arm CT is a revolutionary
      advancement in the intervention radiology suite that allows acquisition of data
      which can be reformatted in multiple planes and volume rendered incorporating
      both soft tissue and vascular information like multidetector computed tomography
      (MDCT). These images acquired during the TACE procedure can provide critical
      inputs for achieving a safe and effective therapy. This case series aims to
      illustrate the utility of C-arm CT in solving specific problems encountered while
      performing TACE. 

PMID- 24851012
TI  - Hyperreactio luteinalis: An often mistaken diagnosis.
AB  - Hyperreactio luteinalis is a rare entity in which there is bilateral, benign,
      functional multicystic ovarian enlargement during pregnancy, which is most
      commonly seen in third trimester. This condition is usually innocuous and does
      not need any specific treatment. However, many a times, it is mistaken for
      ovarian malignancy and inadvertently operated upon. This is a case report of a 24
      year-old female with a partial molar pregnancy associated with hyperreactio
      luteinalis who was followed up for regression of the same and normalization of
      beta human chorionic gonadotropin (hCG) levels. 

PMID- 24851013
TI  - Cobb's collar occurring in two brothers in a family: A rare entity revisited.
AB  - Most urethral strictures arise from iatrogenic, traumatic, or inflammatory
      causes. We report the familial occurrence of a congenital bulbar urethral
      stricture in two brothers. Retrograde and voiding cystourethrography was
      performed. A Cobb's collar was diagnosed after radiological and endoscopic
      evaluation in both cases and was successfully managed with urethroplasty. Cobb's
      collar is a rarely recognized cause of a membranous stricture of bulbar urethra
      that can lead to several urinary problems. In cases of adolescent and young
      adults presenting with symptoms of progressive urinary obstruction and enuresis
      with or without urinary tract infection, Cobb's collar can be seen as a minor
      constriction in the bulbar urethra, but is not frequently symptomatic, and the
      familial occurrence of such a stricture is even rarer. 

PMID- 24851014
TI  - Does standard triple therapy still have a role in first-line Helicobacter pylori
      eradication in Korea?

PMID- 24851015
TI  - Fine, ultrafine, and yellow dust: emerging health problems in Korea.

PMID- 24851017
TI  - Blood cadmium concentration of residents living near abandoned metal mines in
      Korea.
AB  - The purpose of this study was to investigate demographic and lifestyle variables
      and blood cadmium concentrations in residents living near abandoned metal mines
      in Korea. Blood cadmium concentrations were measured in 15,161 subjects living
      around abandoned metal mines (exposed group, n = 14,464) and compared with those
      living in designated control areas (control group, n = 697). A questionnaire was
      provided to all subjects to determine age, gender, mine working history, times of
      residence, smoking habits and dietary water type. The geometric mean (95%
      confidence intervals) of blood cadmium concentration (1.25 [1.24-1.27] ug/L) in
      the exposed group was significantly higher than in the control group (1.17 [1.13
      1.22] ug/L). Mean residence time and mine working history in the exposed group
      were significantly higher than in the control group. Blood cadmium concentrations
      increased with increasing age, and residence time in both groups, and blood
      cadmium concentrations were higher in current-smokers than in non-smokers in both
      groups. This study shows the geometric mean of blood cadmium concentration in
      abandoned mining areas are higher than in non-mining areas in the general adult
      Korean population. 

PMID- 24851016
TI  - Genetic studies in human prion diseases.
AB  - Human prion diseases are fatal neurodegenerative disorders that are characterized
      by spongiform changes, astrogliosis, and the accumulation of an abnormal prion
      protein (PrP(Sc)). Approximately 10%-15% of human prion diseases are familial
      variants that are caused by pathogenic mutations in the prion protein gene
      (PRNP). Point mutations or the insertions of one or more copies of a 24 bp repeat
      are associated with familial human prion diseases including familial Creutzfeldt
      Jakob disease (CJD), Gerstmann-Straussler-Scheinker syndrome, and fatal familial
      insomnia. These mutations vary significantly in frequency between countries.
      Here, we compare the frequency of PRNP mutations between European countries and
      East Asians. Associations between single nucleotide polymorphisms (SNPs) of
      several candidate genes including PRNP and CJD have been reported. The SNP of
      PRNP at codon 129 has been shown to be associated with sporadic, iatrogenic, and
      variant CJD. The SNPs of several genes other than PRNP have been showed
      contradictory results. Case-control studies and genome-wide association studies
      have also been performed to identify candidate genes correlated with variant
      and/or sporadic CJD. This review provides a general overview of the genetic
      mutations and polymorphisms that have been analyzed in association with human
      prion diseases to date. 

PMID- 24851018
TI  - Preoperative selective desensitization of live donor liver transplant recipients
      considering the degree of T lymphocyte cross-match titer, model for end-stage
      liver disease score, and graft liver volume.
AB  - Several studies have suggested that a positive lymphocyte cross-matching (XM) is
      associated with low graft survival rates and a high prevalence of acute rejection
      after adult living donor liver transplantations (ALDLTs) using a small-for-size
      graft. However, there is still no consensus on preoperative desensitization. We
      adopted the desensitization protocol from ABO-incompatible LDLT. We performed
      desensitization for the selected patients according to the degree of T lymphocyte
      cross-match titer, model for end-stage liver disease (MELD) score, and graft
      liver volume. We retrospectively evaluated 230 consecutive ALDLT recipients for 5
      yr. Eleven recipients (4.8%) showed a positive XM. Among them, five patients with
      the high titer (> 1:16) by antihuman globulin-augmented method (T-AHG) and one
      with a low titer but a high MELD score of 36 were selected for desensitization:
      rituximab injection and plasmapheresis before the transplantation. There were no
      major side effects of desensitization. Four of the patients showed successful
      depletion of the T-AHG titer. There was no mortality and hyperacute rejection in
      lymphocyte XM-positive patients, showing no significant difference in survival
      outcome between two groups (P=1.000). In conclusion, this desensitization
      protocol for the selected recipients considering the degree of T lymphocyte cross
      match titer, MELD score, and graft liver volume is feasible and safe. 

PMID- 24851019
TI  - Use of bortezomib as anti-humoral therapy in kidney transplantation.
AB  - This study aimed to investigate the effect of bortezomib in the desensitization
      and treatment of acute antibody mediated rejection (AAMR) in kidney
      transplantation. Nine patients who received bortezomib therapy for
      desensitization (DSZ group, n = 3) or treatment of AAMR (AAMR group, n = 6) were
      included in this study. In the DSZ group, 2 patients required DSZ owing to
      positive cross match and 1 owing to ABO mismatch with high baseline anti-ABO
      antibody titer (1:1,024). Bortezomib was used at 1, 3, 8, and 11 days from the
      start of the treatment. In the AAMR group, 3 patients showed full recovery of
      allograft function after bortezomib use and decrease in donor specific anti-HLA
      antibody (HLA-DSA). However, 3 patients did not respond to bortezomib and
      experienced allograft failure. In the DSZ group, negative conversion of T-CDC
      (complement-dependent cytotoxicity) was achieved, and HLA-DSA was decreased to
      lower than a weak level (median fluorescence intensity [MFI] < 5,000) in 2
      patients. In the case of ABO mismatch kidney transplantation, the anti-A/B
      antibody titer decreased to below the target (<= 1:16) after bortezomib therapy.
      Therefore, bortezomib could be an alternative therapeutic option for
      desensitization and treatment of AAMR that is unresponsive to conventional
      therapies. 

PMID- 24851020
TI  - Pertussis seroprevalence in korean adolescents and adults using anti-pertussis
      toxin immunoglobulin G.
AB  - This study was conducted to evaluate age-specific seroprevalence of pertussis in
      Korea and to formulate a strategy to prevent and reduce the incidence of
      pertussis. Residual serum samples of healthy adolescents and adults 11 yr of age
      or older were collected between July 2012 and December 2012, and anti-pertussis
      toxin (PT) IgG titers were measured using a commercial ELISA kit. We compared the
      mean anti-PT IgG titers and seroprevalence of pertussis of the six age groups: 11
      20, 21-30, 31-40, 41-50, 51-60, and >= 61 yr. A total of 1,192 subjects were
      enrolled. The mean anti-PT IgG titer and pertussis seroprevalence were 35.53 +/-
      62.91 EU/mL and 41.4%, respectively. The mean anti-PT IgG titers and
      seroprevalence were not significantly different between the age groups. However,
      the seroprevalence in individuals 51 yr of age or older was significantly higher
      than in individuals younger than 51 yr (46.5% vs 39.1%, P = 0.017). Based on
      these results, a new pertussis prevention strategy is necessary for older adults.

PMID- 24851021
TI  - Prevention of comorbidity and acute attack of gout by uric acid lowering therapy.
AB  - The object of this study was to evaluate the effect of uric acid lowering therapy
      in reducing the new development of comorbidities and the frequency of acute
      attacks in gout patients. We retrospectively reviewed patients who were diagnosed
      to have gout with at least 3 yr of follow up. They were divided into 2 groups; 53
      patients with mean serum uric acid level (sUA)<6 mg/dL and 147 patients with mean
      sUA>=6 mg/dL. Comorbidities of gout such as hypertension (HTN), type II diabetes
      mellitus (DM), chronic kidney disease, cardiovascular disease (CVD) and
      urolithiasis were compared in each group at baseline and at last follow-up visit.
      Frequency of acute gout attacks were also compared between the groups. During the
      mean follow up period of 7.6 yr, the yearly rate of acute attack and the new
      development of HTN, DM, CVD and urolithiasis was lower in the adequately treated
      group compared to the inadequately treated group. Tight control of uric acid
      decreases the incidence of acute gout attacks and comorbidities of gout such as
      HTN, DM, CVD and urolithiasis. 

PMID- 24851023
TI  - Long-term oncologic outcomes after radical cystectomy for bladder cancer at a
      single institution.
AB  - The aim of this study was to evaluate our experience using radical cystectomy to
      treat patients with bladder cancer and to describe the associations between
      pathologic features and clinical outcomes. All 701 patients who underwent radical
      cystectomy for bladder cancer were evaluated. The patient population consisted of
      623 men and 78 women. The overall 5 and 10 yr recurrence-free survival (RFS)
      rates were 61.8% and 57.7%, respectively, and the 5 and 10 yr cancer-specific
      survival (CSS) rates were 70.8% and 65.1%, respectively. Multivariate analysis
      showed that factors significantly predictive of RFS and CSS included extravesical
      extension (P = 0.001), lymph node metastasis (P = 0.001), and lymphovascular
      invasion (P < 0.001 and P = 0.007). The 5 and 10 yr RFS rates for patients with
      lymph node metastasis were 25.6% and 20.8%, respectively, and the 5 and 10 yr CSS
      rates were 38.6% and 30.9%, respectively. Adjuvant chemotherapy significantly
      improved RFS (P = 0.002) and CSS (P = 0.001) in patients with lymph node
      metastasis. Radical cystectomy provides good survival results in patients with
      invasive bladder cancer. Pathologic features significantly associated with
      prognosis include extravesical extension, node metastasis, and lymphovascular
      invasion. Adjuvant chemotherapy improves survival in patients with advanced stage
      disease. 

PMID- 24851022
TI  - Association between recent acetaminophen use and asthma: modification by
      polymorphism at TLR4.
AB  - The risk of asthma has been increasing in parallel with use of acetaminophen,
      which is a potential source of oxidative stress. Toll-like receptor 4 (TLR4)
      plays a critical role not only in innate immunity, but also in mediating reactive
      oxygen species induced inflammation. Therefore, we investigated associations
      between acetaminophen usage and TLR4 polymorphism on asthma and bronchial
      hyperresponsiveness (BHR). The number of 2,428 elementary school children in
      Seoul and Jeongeup cities was recruited. Subjects who used acetaminophen with a
      family history of asthma had an increased risk of both asthma diagnosis ever and
      current asthma. Individuals with CT+TT genotypes at the TLR4 polymorphism, in
      combination with acetaminophen usage, also demonstrated an increased risk of
      asthma diagnosis ever (aOR, 2.08; 95% confidence interval [CI], 1.10-3.92).
      Family history of asthma and acetaminophen usage were risk factors for BHR.
      Although TLR4 was not an independent risk factor for BHR, individuals with CT+TT
      genotypes at the TLR4 polymorphism had an increased risk of BHR when combined
      with acetaminophen usage (aOR, 1.74; 95% CI, 1.03-2.94). In conclusion,
      acetaminophen usage may be associated with asthma and BHR in genetically
      susceptible subjects. This effect may be modified by polymorphism at TLR4. 

PMID- 24851024
TI  - Papillary thyroid microcarcinomas are different from latent papillary thyroid
      carcinomas at autopsy.
AB  - The aim of this study was to review the literature of latent papillary thyroid
      carcinomas (PTCs) discovered at autopsy and describe the available pathologic and
      demographic differences from a group of papillary thyroid microcarcinomas (PTMCs)
      the reported in a previous publication. We searched the PubMed for published
      articles describing latent thyroid carcinomas detected at autopsy. Meta-analysis
      was performed to identify differences between the clinicopathologic features of
      PTMCs analyzed previously in our institution (Group I) and those of latent PTCs
      described in autopsy studies (Group II). We identified 1,355 patients with PTMC
      (Group I) and 989 with latent PTCs (Group II). Mean patient age was 47.3 yr in
      Group I and 64.5 yr in Group II. The male:female ratio was 1:10.9 in Group I and
      1:1 in Group II. Most PTMCs (67.6%) were larger than 0.5 cm in size, whereas most
      latent PTCs were <1-3 mm in diameter. The rates of multifocality were 24.7% in
      Group I and 30.5% in Group II, and the rates of cervical lymph node metastasis
      were 33.4% in Group I and 10.0% in Group II. Currently available data indicated
      that clinically evident PTMCs differ from latent PTCs detected at autopsy.
      Therefore, these two entities should be regarded as different. 

PMID- 24851025
TI  - Is there any role of positron emission tomography computed tomography for
      predicting resectability of gallbladder cancer?
AB  - The role of integrated (18)F-2-fluoro-2-deoxy-D-glucose positron emission
      tomography computed tomography (PET-CT) is uncertain in gallbladder cancer. The
      aim of this study was to show the role of PET-CT in gallbladder cancer patients.
      Fifty-three patients with gallbladder cancer underwent preoperative computed
      tomography (CT) and PET-CT scans. Their medical records were retrospectively
      reviewed. Twenty-six patients underwent resection. Based on the final outcomes,
      PET-CT was in good agreement (0.61 to 0.80) with resectability whereas CT was in
      acceptable agreement (0.41 to 0.60) with resectability. When the diagnostic
      accuracy of the predictions for resectability was calculated with the ROC curve,
      the accuracy of PET-CT was higher than that of CT in patients who underwent
      surgical resection (P=0.03), however, there was no difference with all patients
      (P=0.12). CT and PET-CT had a discrepancy in assessing curative resection in nine
      patients. These consisted of two false negative and four false positive CT
      results (11.3%) and three false negative PET-CT results (5.1%). PET-CT was in
      good agreement with the final outcomes compared to CT. As a complementary role of
      PEC-CT to CT, PET-CT tended to show better prediction about resectability than
      CT, especially due to unexpected distant metastasis. 

PMID- 24851026
TI  - The relationship between J wave on the surface electrocardiography and
      ventricular fibrillation during acute myocardial infarction.
AB  - We investigated whether the presence of J wave on the surface electrocardiography
      (sECG) could be a potential risk factor for ventricular fibrillation (VF) during
      acute myocardial infarction (AMI). We performed a retrospective study of 317
      patients diagnosed with AMI in a single center from 2009 to 2012. Among the
      enrolled 296 patients, 22 (13.5%) patients were selected as a VF group. The J
      wave on the sECG was defined as a J point elevation manifested through QRS
      notching or slurring at least 1 mm above the baseline in at least two leads. We
      found that the incidence of J wave on the sECG was significantly higher in the VF
      group. We also confirmed that several conventional risk factors of VF were
      significantly related to VF during AMI; time delays from the onset of chest pain,
      blood concentrations of creatine phosphokinase and incidence of ST-segment
      elevation. Multiple logistic regression analysis demonstrated that the presence
      of J wave and the presence of a ST-segment elevation were independent predictors
      of VF during AMI. This study demonstrated that the presence of J wave on the sECG
      is significantly related to VF during AMI. 

PMID- 24851027
TI  - Alkali therapy attenuates the progression of kidney injury via Na/H exchanger
      inhibition in 5/6 nephrectomized rats.
AB  - Metabolic acidosis is a cause of renal disease progression, and alkali therapy
      ameliorates its progression. However, there are few reports on the role of renal
      acid-base transporters during alkali therapy. We evaluated the effect of sodium
      bicarbonate therapy and the role of acid-base transporters on renal disease
      progression in rats with a remnant kidney. Sprague-Dawley rats consumed dietary
      sodium bicarbonate (NaHCO3) or sodium chloride (NaCl) with 20% casein after a 5/6
      nephrectomy. After being provided with a casein diet, the NaHCO3-treated group
      had higher levels of serum bicarbonate than the control group. At week 4, the
      glomerular filtration rate in the NaHCO3 group was higher than that in the NaCl
      group, and the difference became prominent at week 10. The glomerulosclerosis and
      tubulointerstitial damage indices in the NaHCO3 group were less severe compared
      with controls at week 4 and 10. The expression of the Na/H exchanger (NHE) was
      decreased, and apical reactivity was decreased in the NaHCO3 group, compared with
      the NaCl group. Endothelin-1 levels in the kidney were also decreased in the
      NaHCO3 group. Dietary sodium bicarbonate has the effects of ameliorating renal
      disease progression, which may be related to the altered expression of NHE in the
      remaining kidney. 

PMID- 24851028
TI  - The clinical characteristics of colonic pseudo-obstruction and the factors
      associated with medical treatment response: a study based on a multicenter
      database in Korea.
AB  - Colonic pseudo-obstruction (CPO) is defined as marked colonic distension in the
      absence of mechanical obstruction. We aimed to investigate the clinical
      characteristics of CPO and the factors associated with the response to medical
      treatment by using a multicenter database in Korea. CPO was diagnosed as colonic
      dilatation without mechanical obstruction by using radiologic and/or endoscopic
      examinations. Acute CPO occurring in the postoperative period in surgical
      patients or as a response to an acute illness was excluded. CPO cases were
      identified in 15 tertiary referral hospitals between 2000 and 2011. The patients'
      data were retrospectively reviewed and analyzed. In total, 104 patients (53 men;
      mean age at diagnosis, 47 yr) were identified. Seventy-seven of 104 patients
      (74%) showed a transition zone on abdominal computed tomography. Sixty of 104
      patients (58%) showed poor responses to medical treatment and underwent surgery
      at the mean follow-up of 7.4 months (0.5-61 months). Younger age at the time of
      diagnosis, abdominal distension as a chief complaint, and greater cecal diameter
      were independently associated with the poor responses to medical treatment. These
      may be risk factors for a poor response to medical treatment. 

PMID- 24851029
TI  - Meta-analysis of first-line triple therapy for helicobacter pylori eradication in
      Korea: is it time to change?
AB  - Proton pump inhibitor (PPI)-based triple therapy consisting of PPI, amoxicillin,
      and clarithromycin, is the recommended first-line treatment for Helicobacter
      pylori infection. However, the eradication rate of triple therapy has declined
      over the past few decades. We analyzed the eradication rate and adverse events of
      triple therapy to evaluate current practices in Korea. A comprehensive literature
      search was performed up to August 2013 of 104 relevant studies comprising 42,124
      patients. The overall eradication rate was 74.6% (95% confidence interval [CI],
      72.1%-77.2%) by intention-to-treat analysis and 82.0% (95% CI, 80.8%-83.2%) by
      per-protocol analysis. The eradication rate decreased significantly from 1998 to
      2013 (P < 0.001 for both intention-to-treat and per-protocol analyses). Adverse
      events were reported in 41 studies with 8,018 subjects with an overall incidence
      rate of 20.4% (95% CI, 19.6%-21.3%). The available data suggest that the
      effectiveness of standard triple therapy for H. pylori eradication has decreased
      to an unacceptable level. A novel therapeutic strategy is warranted to improve
      the effectiveness of first-line treatment for H. pylori infection in Korea. 

PMID- 24851030
TI  - Difference of the naltrexone's effects in social drinkers by spicy food
      preference.
AB  - The purpose of this study was to investigate the differences in subjective acute
      effects of alcohol and naltrexone among those who prefer spicy food to varying
      degrees. Acute biphasic alcohol effects scale (BAES), visual analogue scale for
      craving (VAS-C), blood alcohol concentration (BAC) and food preference scale were
      measured in 26 men. Repeated measures ANOVA (2 preference groups*4 time blocks)
      on the stimulative subscale of BAES revealed a significant group by block
      interaction in naltrexone condition (N+) (P<0.001), but not in non-naltrexone
      condition (N-). Furthermore, repeated measures ANOVA (2 drug groups*4 time
      blocks) on the stimulative subscale of BAES revealed a significant group by block
      interaction in strong preference for spicy food (SP) (P<0.001), but not in lesser
      preference for spicy food (LP). The paired t-test revealed that significant
      suppression of the stimulative subscale of BAES was observed at 15 min (P<0.001)
      and 30 min (P<0.001) after drinking when N+ compared with N- in SP. For those who
      prefer spicy food, the stimulative effect of acute alcohol administration was
      suppressed by naltrexone. This result suggests that the effect of naltrexone may
      vary according to spicy food preference. 

PMID- 24851031
TI  - Patterns of antipsychotic prescription to patients with schizophrenia in Korea:
      results from the health insurance review & assessment service-national patient
      sample.
AB  - This study aimed to analyze the patterns of antipsychotic prescription to
      patients with schizophrenia in Korea. Using the Health Insurance Review &
      Assessment Service-National Patients Sample (HIRA-NPS), which was a stratified
      sampling from the entire population under the Korean national health security
      system (2009), descriptive statistics for the patterns of the monopharmacy and
      polypharmacy, neuropsychiatric co-medications, and prescribed individual
      antipsychotic for patients with schizophrenia were performed. Comparisons of
      socioeconomic and clinical factors were performed among patients prescribed only
      with first- and second-generation antipsychotics. Of 126,961 patients with
      schizophrenia (age 18-80 yr), 13,369 were prescribed with antipsychotic
      monopharmacy and the rest 113,592 with polypharmacy. Two or more antipsychotics
      were prescribed to 31.34% of the patients. Antiparkinson medications (66.60%),
      anxiolytics (65.42%), mood stabilizers (36.74%), and antidepressants (25.90%)
      were co-medicated. Patients who were prescribed only with first-generation
      antipsychotics (n=26,254) were characterized by significantly older age, greater
      proportion of male, higher proportion of medicaid, higher total medical cost,
      lower self-payment cost, and higher co-medication rates of antiparkinson agents
      and anxiolytics than those who were prescribed only with second-generation
      antipsychotics (n=67,361). In this study, it has been reported substantial
      prescription rates of first-generation antipsychotics and antipsychotic
      polypharmacy and relatively small prescription rate of clozapine to patients with
      schizophrenia. Since this study has firstly presented the patterns of
      antipsychotic prescription to schizophrenic patients in Korean national
      population, the findings of this study can be compared with those of later
      investigations about this theme. 

PMID- 24851032
TI  - Serum leptin and adiponectin levels in Korean patients with psoriasis.
AB  - Psoriasis is a disorder caused by genetic and immunological factors. Leptin, a
      peptide hormone secreted predominantly from adipose tissue, regulates energy
      intake and expenditure, as well as the T-helper response. There have been
      conflicting reports regarding serum levels of leptin and adiponectin in patients
      with psoriasis. In the present study, we measured serum levels of leptin and
      adiponectin in Korean patients with psoriasis. Twenty-four patients with
      psoriasis and fifteen control subjects were included in the study. Serum leptin
      and adiponectin levels were determined by an immunometric sandwich enzyme-linked
      immunosorbent assay (ELISA). The mean serum leptin concentration in patients with
      psoriasis was higher than in controls, and the difference was statistically
      significant. In contrast, serum adiponectin levels in patients with psoriasis
      were significantly decreased compared with healthy controls. Leptin levels in
      vitamin D-deficient patients were statistically significantly higher than in
      vitamin D-sufficient patients. Serum adiponectin concentrations showed a negative
      correlation with body mass index (BMI) and psoriasis area and severity index
      (PASI) in patients with psoriasis. In conclusion, the present study demonstrated
      that leptin and adiponectin may play a role in the immunopathogenesis of
      psoriasis and may be useful biomarkers indicating severity of psoriasis in Korean
      patients. 

PMID- 24851033
TI  - Thrombolytic therapy complemented by ECMO: successful treatment for a case of
      massive pulmonary thromboembolism with hemodynamic collapse.
AB  - Pulmonary thromboembolism (PTE) is a common clinical condition related to
      significant mortality. Furthermore, patients with PTE presenting with right heart
      thrombus show higher mortality due to rapid hemodynamic deterioration. But the
      optimal treatment of massive PTE is controversial although various methods have
      been developed and improved. Here, we presented a case of 56-yr-old woman with
      massive PTE showing hemodynamic collapse, who was successfully treated with
      extracorporeal membrane oxygenation (ECMO) adjunct to thrombolytic therapy even
      without thrombectomy. ECMO was useful for resuscitation and stabilization of the
      cardiopulmonary function. In conclusion, thrombolytic therapy complemented by
      ECMO may be an effective treatment option for acute massive PTE with hemodynamic
      instability. 

PMID- 24851034
TI  - Gastroplasty for esophageal perforation after endoscopic balloon dilatation for
      achalasia: two cases.
AB  - Esophageal perforation after endoscopic forceful pneumatic dilatation for
      achalasia is a devastating complication and surgical treatment is necessary. A 65
      yr-old man and a 54-yr-old woman referred for esophageal perforation two hours
      after pneumatic dilatation and during the procedure, respectively. Gastroplasties
      through thoracotomy were performed in both cases and their recoveries were
      uneventful. The esophagogram with gastrografin on the post-operative 8th day did
      not show any passage disturbance or leakage at the anastomosis site. On the
      follow-up endoscopy 4 to 6 months after operation revealed that reflux
      esophagitis of LA classification A were noted in the both patients. They did not
      complain any reflux symptom or dysphagia for 9 to 13 months after operation.
      Instead of the most widely used procedure; primary repair of perforation site,
      wrapping with intercostal muscle flap and esophagomyotomy, gastroplasty was
      performed in two cases of iatrogenic esophageal perforation in achalasia and
      experienced good results. 

PMID- 24851036
TI  - Response to Intervention (RTI) Services: An Ecobehavioral Perspective.
AB  - School-wide Response to Intervention (RTI) services are growing in prevalence in
      U.S. schools. Most advanced are RTI programs in elementary schools, with
      preschool and secondary education programs beginning to discuss, develop, and
      experiment with school-wide RTI. At its heart, RTI seeks to account for
      individual differences in student learning success by discovering the
      instructional situations in which each student learns best and providing them for
      all who need them. RTI is an early intervening approach to the prevention of
      learning and behavior problems before they become disabilities later. The
      implementation of school-wide RTI approaches reorganizes school ecology at
      multiple levels and when implemented with fidelity, RTI schools have a
      distinctive "ecological footprint" that differentiates them from traditional, non
      RTI schools. Implementers of RTI need consultation that provides them with
      information on the structure and function of their programs for use in problem
      solving and decision making. The purpose of this paper is to describe RTI and
      illustrate an ecobehavioral approach to providing RTI school staff with
      information they need.

PMID- 24851035
TI  - Methylenetetrahydrofolate reductase 677 genotype-specific reference values for
      plasma homocysteine and serum folate concentrations in korean population aged 45
      to 74 years: the Namwon study.
AB  - The reference interval for plasma total homocysteine (tHcy) and serum folate
      concentrations were estimated. Total of 3,154 reference individuals (1,029 men
      and 2,125 women) were selected based on stringent exclusion criteria. For plasma
      tHcy concentration (uM/L), reference values (median [5-95 percentile]) were 7.72
      (5.03 to 13.80) and 6.09 (3.95-10.19) in men and women, respectively. For serum
      folate concentration (nM/L), reference values were 23.71 (11.73-38.44) and 28.95
      (15.23-40.44) in men and women, respectively. The tHcy levels of both genders in
      the present study were lower than those in previous reports from other countries
      and Korea. 

PMID- 24851037
TI  - Upregulation of inflammatory genes in the nasal mucosa of patients undergoing
      endonasal dacryocystorhinostomy.
AB  - BACKGROUND: Epiphora is a common complaint of nasolacrimal duct obstruction
      (NLDO) in adults. The precise pathogenesis of NLDO is still unknown, but
      inflammatory processes are believed to be predisposing factors. Endoscopic
      dacryocystorhinostomy (EN-DCR) is an effective surgical technique for treating
      symptomatic NLDO. The purpose of the procedure is to relieve the patient's
      symptoms by creating an opening, ie, a rhinostoma, between the lacrimal sac and
      the nasal cavity. Although the success rates after EN-DCR are high, the procedure
      sometimes fails due to onset of a fibrotic process at the rhinostomy site. The
      aim of this prospective comparative study was to investigate inflammation-related
      gene expression in the nasal mucosa at the rhinostomy site. METHODS: Ten
      participants were consecutively recruited from eligible adult patients who
      underwent primary powered EN-DCR (five patients) or septoplasty (five controls).
      Nasal mucosa specimens were taken from the rhinostomy site at the beginning of
      surgery for analysis of gene expression. Specimens were taken from the same site
      on the lateral nasal wall for controls. Quantitative reverse transcription
      polymerase chain reaction (qRT-PCR) was performed for the inflammatory genes
      interleukin (IL)-6, IL-1beta, and CCL2, and because of a clear trend of increased
      inflammation in the EN-DCR samples, a wider PCR array was performed to compare
      inflammation-related gene expression in EN-DCR subjects and corresponding
      controls. RESULTS: Our qRT-PCR results revealed a clear trend of increased
      transcription of IL-6, IL-1beta, and CCL2 (P=0.03). The same trend was also
      evident in the PCR array, which additionally revealed notable differences between
      EN-DCR subjects and controls with regard to expression of several other
      inflammation-related mediators. At 6-month follow-up, the success rate after
      primary EN-DCR was 60%, ie, in three of five patients. CONCLUSION: The present
      study demonstrates that there is an intense inflammation gene expression response
      in the nasal mucosa of patients undergoing EN-DCR.

PMID- 24851038
TI  - Profile of ocriplasmin and its potential in the treatment of vitreomacular
      adhesion.
AB  - The recent approval by the US Food and Drug Administration of ocriplasmin for the
      treatment of symptomatic vitreomacular adhesion (VMA), often associated with
      vitreomacular traction (VMT) and macular hole (MH), has brought new attention to
      the field of pharmacologic vitreolysis. The need for an enzyme to split the
      vitreomacular interface, which is formed by a strong adhesive interaction between
      the posterior vitreous cortex and the internal limiting membrane, historically
      stems from pediatric eye surgery. This review summarizes the different anatomic
      classifications of posterior vitreous detachment or anomalous posterior vitreous
      detachment and puts these in the context of clinical pathologies commonly
      observed in clinical practice of the vitreoretinal specialist, such as MH, VMT,
      age-related macular degeneration, and diabetic macular edema. We revisit the
      outcome of the Phase II studies that indicated ocriplasmin was a safe and
      effective treatment for selected cases of symptomatic VMA and MH. Release of VMA
      at day 28 was achieved by 26.5% of patients in the ocriplasmin group versus 10.1%
      in the placebo group (P<0.001). Interestingly, for MHs, the numbers were more
      remarkable. Predictive factors for successful ocriplasmin treatment were
      identified for VMT (VMA diameter smaller than 1,500 MUm) and MH (smaller than 250
      MUm). In comparison with the highly predictable outcome after vitrectomy, the
      general success rate of ocriplasmin not under clinical trial conditions has not
      fully met expectations and needs to be proven in real-world clinical settings.
      The ocriplasmin data will be compared in the future with observational data on
      spontaneous VMA release, will help retina specialists make more accurate
      predictions, and will improve outcome rates. 

PMID- 24851039
TI  - Clinical efficacy of Spasmofen(r) suppository in the emergency treatment of renal
      colic: a randomized, double-blind, double-dummy comparative trial.
AB  - BACKGROUND: Renal colic is typically characterized by the sudden onset of severe
      pain radiating from the flank to the groin and its acute management in emergency
      departments essentially aims at rapid pain relief. Spasmofen((r)) is a brand of
      Amriya Pharmaceutical Industries in the form of rectal suppositories containing
      ketoprofen 100 mg and hyoscine butylbromide 10 mg. This combination is intended
      for the rapid relief of severe colicky pain in the renal system, hepatobiliary
      system, or gastrointestinal tract. This trial aims to compare a single-dose of
      Spasmofen rectal suppository to a single intravenous (IV) ketorolac tromethamine
      30 mg/2 mL dose in patients with acute renal colic. METHODS: A total of 80
      eligible consecutive patients presenting to the emergency departments of two
      medical centers with acute renal colic were included in the study. Eligible
      patients who signed the informed consent were randomly assigned into two
      treatment groups: an experimental group (Spasmofen group) who received one
      Spasmofen rectal suppository plus an IV injection of 2 mL of normal saline
      solution; and a control group (ketorolac group) who received one ketorolac 30
      mg/2 mL ampoule IV plus one placebo suppository. Treatment success, defined as a
      change in the verbal rating score from severe or moderate pain to none or mild at
      60 minutes after the dose, was compared between groups using the chi
      square/Fisher's exact test. Percentage reductions in visual pain analog scale
      (VPAS) scores at 15 and 60 minutes after the dose were compared between groups
      using the Z-test for proportions. RESULTS: Successful treatment at 60 minutes
      occurred in 35 of 40 (87.5%) of Spasmofen-treated patients and in 33 of 40
      (82.5%) of ketorolac-treated patients. The difference was not statistically
      significant by Fisher's exact test (P=0.755). The mean percentage reduction of
      VPAS after 15 minutes was 61.82% in the Spasmofen-treated group and 64.76% in the
      ketorolac-treated group. The difference was also not statistically significant by
      the Z-test for proportions (P=0.795). Sixty minutes after being treated,
      Spasmofen was associated with a statistically significant greater reduction in
      VPAS (mean% reduction =92.36%) than ketorolac (75.06%; P=0.0466). CONCLUSION:
      Single-dose Spasmofen rectal suppository might be a safe and effective first-aid
      treatment for the emergency department relief of acute renal colic.

PMID- 24851040
TI  - Combined isosorbide dinitrate and ibuprofen as a novel therapy for muscular
      dystrophies: evidence from Phase I studies in healthy volunteers.
AB  - We designed two Phase I studies that assessed healthy volunteers in order to
      evaluate the safety and to optimize the dosing of the combination of the drugs
      isosorbide dinitrate, a nitric oxide donor, and ibuprofen, a nonsteroidal
      antiinflammatory drug. We designed these studies with the aim of designing a
      Phase II trial to evaluate the drugs' efficacy in patients affected by Duchenne
      muscular dystrophy. For the first trial, ISOFEN1, a single-dose, randomized
      sequence, open-label, active control, three-treatment cross-over study, was aimed
      at comparing the pharmacokinetics of ibuprofen 200 mg and isosorbide dinitrate 20
      mg when given alone and concomitantly. The pharmacokinetics of ibuprofen given
      alone versus ibuprofen given concomitantly with isosorbide dinitrate were
      similar, as documented by the lack of statistically significant differences in
      the main drug's pharmacokinetic parameters (time to maximal concentration [Tmax],
      maximal concentration [Cmax], area under the curve [AUC]0-t, and AUC0-infinity).
      Similarly, we found that the coadministration of ibuprofen did not significantly
      affect the pharmacokinetics of isosorbide dinitrate. No issues of safety were
      detected. The second trial, ISOFEN2, was a single-site, dose titration study that
      was designed to select the maximum tolerated dose for isosorbide dinitrate when
      coadministered with ibuprofen. Eighteen out of the 19 enrolled subjects tolerated
      the treatment well, and they completed the study at the highest dose of
      isosorbide dinitrate applied (80 mg/day). One subject voluntarily decided to
      reduce the dose of isosorbide dinitrate from 80 mg to 60 mg. The treatment
      related adverse events recorded during the study were, for the large majority,
      episodes of headache that remitted spontaneously in 0.5-1 hour - a known side
      effect of isosorbide dinitrate. These studies demonstrate that the combination of
      isosorbide dinitrate and ibuprofen does not lead to pharmacokinetic interactions
      between the two drugs; they also demonstrate that the combination of isosorbide
      dinitrate and ibuprofen has optimal tolerability and safety profiles that are
      similar to those previously reported for isosorbide dinitrate and ibuprofen given
      alone. 

PMID- 24851041
TI  - Topical infliximab for the suppression of wound healing following experimental
      glaucoma filtration surgery.
AB  - BACKGROUND: The purpose of this work was to look into the effects of infliximab
      on wound healing in experimental glaucoma filtration surgery and to compare the
      antifibrotic effects of this agent to that of mitomycin-C (MMC). METHODS: Twenty
      eight male New Zealand White rabbits were randomly assigned to four groups, each
      including seven rabbits: control group, sham group, MMC group, and infliximab
      group. The rabbits in the control group were not operated on and did not receive
      any treatment. The rabbits in the sham group underwent trabeculectomy and had one
      drop of saline instilled four times a day for 14 days. The rabbits in the MMC
      treatment group underwent trabeculectomy, and a sponge soaked in 0.4 mg/mL MMC
      was applied intraoperatively to the scleral surgical site for three minutes. The
      rabbits in the infliximab treatment group underwent trabeculectomy and one drop
      of 10 mg/mL infliximab was instilled four times a day for 14 days after surgery.
      On day 14 of the experiment, the operated and control eyes were enucleated and
      histologically and immunohistochemically analyzed. RESULTS: The mean fibroblast
      and mononuclear cell (MNC) numbers and the mean immunostaining intensities of
      transforming growth factor-beta (TGF-beta), fibroblast growth factor-beta (FGF
      beta), and platelet-derived growth factor (PDGF) in the sham group were higher
      than those of the control group (P<0.01). The mean fibroblast and MNC numbers and
      the mean immunostaining intensities of TGF-beta, FGF-beta, and PDGF in the MMC
      and infliximab groups were statistically significantly lower than those of the
      sham group (P<0.01). The mean fibroblast and MNC numbers and the mean TGF-beta,
      FGF-beta, and PDGF immunostaining intensities of the MMC and infliximab groups
      were similar (P>0.05). CONCLUSION: Our study suggests that topical infliximab
      effectively suppresses the subconjunctival wound healing response after
      experimental glaucoma filtration surgery, reducing the MNC and fibroblast numbers
      and immunostaining intensities of TGF-beta, FGF-beta, and PDGF.

PMID- 24851042
TI  - Linagliptin: from bench to bedside.
AB  - PURPOSE: The nature of biomedical research affords a broad range of
      investigational topics at the preclinical stage, not all of which may be explored
      in subsequent clinical studies. To provide a comprehensive perspective on the
      physiologic effects of the dipeptidyl peptidase-4 inhibitor linagliptin, this
      review will discuss the results of both preclinical and clinical research,
      summarizing data describing outcomes associated with its use. SUMMARY: Clinical
      studies demonstrate an overall favorable safety profile, low risk for
      hypoglycemia, weight neutrality, primarily nonrenal clearance, and efficacy for
      glycosylated hemoglobin reduction, typically ranging from 0.6% to 0.8% depending
      on baseline levels. In addition to these characteristics, preclinical research on
      linagliptin has yielded several interesting findings such as improved wound
      healing, reduced hepatic fat content, decreased infarct size following myocardial
      infarction or intracranial stroke, and improved vascular function with decreased
      oxidative stress. In accordance with its preclinical profile, linagliptin is
      unique among available dipeptidyl peptidase-4 compounds because it does not
      require dose adjustment when used in patients with renal dysfunction. Reduction
      of albuminuria with linagliptin on top of inhibitors of the renin-angiotensin
      aldosterone system in both preclinical and post hoc clinical analysis serves as
      the foundation for ongoing clinical trials. CONCLUSION: In addition to its
      efficacy for glycemic control, current literature points to other potential
      opportunities associated with linagliptin therapy. These results warrant further
      investigation and underscore the importance of translational study based on
      findings from preclinical research. Moving forward, we can expect that future
      research on linagliptin and other incretin-based therapies will continue to
      expand their applications beyond the maintenance of glycemic control in patients
      with type 2 diabetes.

PMID- 24851043
TI  - Psychosocial predictors of non-adherence to chronic medication: systematic review
      of longitudinal studies.
AB  - OBJECTIVES: Several cross-sectional studies suggest that psychosocial factors are
      associated with non-adherence to chronic preventive maintenance medication
      (CPMM); however, results from longitudinal associations have not yet been
      systematically summarized. Therefore, the objective of this study was to
      systematically synthesize evidence of longitudinal associations between
      psychosocial predictors and CPMM non-adherence. MATERIALS AND METHODS: PUBMED,
      EMBASE, CINAHL, and PsychINFO databases were searched for studies meeting our
      inclusion criteria. The reference lists and the ISI Web of Knowledge of the
      included studies were checked. Studies were included if they had an English
      abstract, involved adult populations using CPMM living in Western countries, and
      if they investigated associations between psychosocial predictors and medication
      non-adherence using longitudinal designs. Data were extracted according to a
      literature-based extraction form. Study quality was independently judged by two
      researchers using a framework comprising six bias domains. Studies were
      considered to be of high quality if >=four domains were free of bias.
      Psychosocial predictors for non-adherence were categorized into five pre-defined
      categories: beliefs/cognitions; coping styles; social influences and social
      support; personality traits; and psychosocial well-being. A qualitative best
      evidence synthesis was performed to synthesize evidence of longitudinal
      associations between psychosocial predictors and CPMM non-adherence. RESULTS: Of
      4,732 initially-identified studies, 30 (low-quality) studies were included in the
      systematic review. The qualitative best evidence synthesis demonstrated limited
      evidence for absence of a longitudinal association between CPMM non-adherence and
      the psychosocial categories. The strength of evidence for the review's findings
      is limited by the low quality of included studies. CONCLUSION: The results do not
      provide psychosocial targets for the development of new interventions in clinical
      practice. This review clearly demonstrates the need for high-quality,
      longitudinal research to identify psychosocial predictors of medication non
      adherence.

PMID- 24851044
TI  - An online survey to study the relationship between patients' health literacy and
      coping style and their preferences for self-management-related information.
AB  - OBJECTIVE: To evaluate patients' preferences for message features and assess
      their relationships with health literacy, monitor-blunter coping style, and other
      patient-dependent characteristics. METHODS: Patients with coronary heart disease
      completed an internet-based survey, which assessed health literacy and monitor
      blunter coping style, as well as various other patient characteristics such as
      sociodemographics, disease history, and explicit information preferences. To
      assess preferences for message features, nine text sets differing in one of nine
      message features were composed, and participants were asked to state their
      preferences. RESULTS: The survey was completed by 213 patients. For three of the
      nine text sets, a relationship was found between patient preference and health
      literacy or monitor-blunter coping style. Patients with low health literacy
      preferred the text based on patient experience. Patients with a monitoring coping
      style preferred information on short-term effects of their treatment and
      mentioning of explicit risks. Various other patient characteristics such as
      marital status, social support, disease history, and age also showed a strong
      association. CONCLUSION: Individual differences exist in patients' preferences
      for message features, and these preferences relate to patient characteristics
      such as health literacy and monitor-blunter coping style.

PMID- 24851045
TI  - Profile of sapacitabine: potential for the treatment of newly diagnosed acute
      myeloid leukemia in elderly patients.
AB  - Acute myeloid leukemia (AML) is a hematopoietic stem cell disorder that affects
      approximately 14,000 persons each year in the US. AML occurs at all ages but the
      incidence increases with age with the median age at diagnosis being 67 years.
      Advances in the treatment of AML over the past decades have led to improved
      survival, albeit mostly in younger patients. The prognosis of older patients with
      this disease over the same time span has not changed much and remains dismal.
      This review focuses on the epidemiology and characteristics of AML in elderly
      patients, the rationale for treating elderly AML patients, and the currently
      available and potential future treatment options such as sapacitabine. Elderly
      AML patients treated with intensive chemotherapy have a higher mortality rate,
      and a lower rate of complete remission and overall survival when compared to the
      younger population. This is due to both the different biology of the disease and
      the number of patient-specific factors. However, elderly AML patients treated
      with aggressive chemotherapy can achieve durable remissions, which offer
      prolonged survival and improved quality of life. Recent data also indicates that
      elderly AML patients deemed unfit for intensive chemotherapy benefit from
      leukemia-specific attenuated dose chemotherapy compared to supportive care alone.
      This has led to renewed interest to look for anti-leukemic therapies designed
      specifically for older patients. Sapacitabine, a novel oral nucleoside analog,
      promises good efficacy, favorable toxicity profile, and ease of administration;
      all of which makes it very appealing. Results from pre-clinical and clinical
      studies have been very encouraging and sapacitabine is currently being evaluated
      in a Phase III study, of which the results are eagerly awaited. 

PMID- 24851046
TI  - Living in negotiation: patients' experiences of being in the diagnostic process
      of COPD.
AB  - PURPOSE: To illuminate patients' lived experiences of going through the process
      of being diagnosed with chronic obstructive pulmonary disease (COPD). PATIENTS
      AND METHODS: A phenomenological-hermeneutic analysis was applied in the
      interpretation of interviews with eight persons diagnosed with mild or moderate
      COPD. RESULTS: One main theme 'living in negotiation', and three themes 'living
      with a body out of step with the diagnosis', 'dealing with the past', and 'being
      challenged by the future' reflected the process participants were living through
      in their quest for acceptance and a new balance in life. Participants found that
      the diagnostic processes were confusing, and that the diagnosis itself was 'a
      slap in the face'. Unclear messages gave rise to fluctuating between an
      understanding of the condition as 'not too severe', insecurity, and fear. Shame
      and guilt related to the diagnosis had origins in the past, and in combination
      with the idea of 'chronic' the COPD diagnosis interfered with the present moment
      and gave rise to uncertainty for the future. The understanding of the present is
      related to negotiations not only with the past, but also with the future. Thus
      temporal aspects of the diagnosis are of great significance for the process of
      finding acceptance. CONCLUSION: Regardless of disease severity, the diagnosis
      seems to be a breakdown of life, which puts life itself at stake. Medical
      professionals should be aware that the way the diagnosis is disclosed and
      communicated has considerable significance for how individuals understand and
      deal with their illness. The diagnosis should be communicated face-to-face,
      clearly and with empathy, and followed by information about COPD. Physicians
      should allow time and listen to the patients' stories, and thus develop a shared
      understanding of the temporal aspect of the illness and patients' needs and
      concerns. Thus, good communication is essential in determining whether the
      patient remains in negotiation, or enters a process toward acceptance and new
      understanding.

PMID- 24851047
TI  - Role of the charge, carbon chain length, and content of surfactant on the skin
      penetration of meloxicam-loaded liposomes.
AB  - The objective of this study was to investigate the influence of surfactant
      charge, surfactant carbon chain length, and surfactant content on the
      physicochemical characteristics (ie, vesicle size, zeta potential, elasticity,
      and entrapment efficiency), morphology, stability, and in vitro skin permeability
      of meloxicam (MX)-loaded liposome. Moreover, the mechanism for the liposome
      enhanced skin permeation of MX was determined by Fourier transform infrared
      spectroscopy and differential scanning calorimetry. The model formulation used in
      this study was obtained using a response surface method incorporating
      multivariate spline interpolation (RSM-S). Liposome formulations with varying
      surfactant charge (anionic, neutral, and cationic), surfactant carbon chain
      length (C4, C12, and C16), and surfactant content (10%, 20%, and 29%) were
      prepared. The formulation comprising 29% cationic surfactant with a C16 chain
      length was found to be the optimal liposome for the transdermal delivery of MX.
      The skin permeation flux of the optimal formulation was 2.69-fold higher than
      that of a conventional liposome formulation. Our study revealed that surfactants
      affected the physicochemical characteristics, stability, and skin permeability of
      MX-loaded liposomes. These findings provide important fundamental information for
      the development of liposomes as transdermal drug delivery systems. 

PMID- 24851048
TI  - Preparation of biocompatible heat-labile enterotoxin subunit B-bovine serum
      albumin nanoparticles for improving tumor-targeted drug delivery via heat-labile
      enterotoxin subunit B mediation.
AB  - Heat-labile enterotoxin subunit B (LTB) is a non-catalytic protein from a
      pentameric subunit of Escherichia coli. Based on its function of binding
      specifically to ganglioside GM1 on the surface of cells, a novel nanoparticle
      (NP) composed of a mixture of bovine serum albumin (BSA) and LTB was designed for
      targeted delivery of 5-fluorouracil to tumor cells. BSA-LTB NPs were
      characterized by determination of their particle size, polydispersity,
      morphology, drug encapsulation efficiency, and drug release behavior in vitro.
      The internalization of fluorescein isothiocyanate-labeled BSA-LTB NPs into cells
      was observed using fluorescent imaging. Results showed that BSA-LTB NPs presented
      a narrow size distribution with an average hydrodynamic diameter of approximately
      254+/-19 nm and a mean zeta potential of approximately -19.95+/-0.94 mV. In
      addition, approximately 80.1% of drug was encapsulated in NPs and released in the
      biphasic pattern. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide (MTT) assay showed that BSA-LTB NPs exhibited higher cytotoxic activity
      than non-targeted NPs (BSA NPs) in SMMC-7721 cells. Fluorescent imaging results
      proved that, compared with BSA NPs, BSA-LTB NPs could greatly enhance cellular
      uptake. Hence, the results indicate that BSA-LTB NPs could be a potential
      nanocarrier to improve targeted delivery of 5-fluorouracil to tumor cells via
      mediation of LTB. 

PMID- 24851049
TI  - Dissociative symptoms reflect levels of tumor necrosis factor alpha in patients
      with unipolar depression.
AB  - Recent evidence indicates that the nature of interactions between the nervous
      system and immune system is important in the pathogenesis of depression.
      Specifically, alterations in pro-inflammatory cytokines have been related to the
      development of several psychological and neurobiological manifestations of
      depressive disorder, as well as to stress exposure. A number of findings point to
      tumor necrosis factor alpha (TNF-alpha) as one of the central factors in these
      processes. Accordingly, in the present study, we test the hypothesis that
      specific influences of chronic stressors related to traumatic stress and
      dissociation are related to alterations in TNF-alpha levels. We performed
      psychometric measurement of depression (Beck Depression Inventory [BDI]-II),
      traumatic stress symptoms (Trauma Symptom Checklist [TSC]-40), and psychological
      and somatoform dissociation (Dissociative Experiences Scale [DES] and Somatoform
      Dissociation Questionnaire [SDQ]-20, respectively), and immunochemical measure of
      serum TNF-alpha in 66 inpatients with unipolar depression (mean age 43.1 +/- 7.3
      years). The results show that TNF-alpha is significantly related to DES (Spearman
      R=-0.42, P<0.01), SDQ-20 (Spearman R=-0.38, P<0.01), and TSC-40 (Spearman R=
      0.41, P<0.01), but not to BDI-II. Results of the present study suggest that TNF
      alpha levels are related to dissociative symptoms and stress exposure in
      depressed patients. 

PMID- 24851050
TI  - Efficacy versus safety: the dilemma of using novel platelet inhibitors for the
      treatment of patients with ischemic stroke and coronary artery disease.
AB  - Coronary and cerebrovascular atherothrombosis are the leading cause of mortality
      and morbidity worldwide. Novel antiplatelet agents have been established for the
      management of patients with clinically evident coronary atherothrombosis and are
      increasingly used in these patients. These agents, however, have shown limited
      efficacy in the prevention of cerebrovascular events and potential harm in
      patients with history of stroke or transient ischemic attack. Herein, the
      efficacy and safety of two established antiplatelet agents in patients with
      stroke - aspirin and clopidogrel - are reviewed with a focus on the use and
      challenges related to novel antiplatelet agents - prasugrel, ticagrelor, and
      vorapaxar - in patients at risk for and with a history of stroke or transient
      ischemic attack. 

PMID- 24851051
TI  - Limitations of real-world treatment with atorvastatin monotherapy for lowering
      LDL-C in high-risk cardiovascular patients in the US.
AB  - BACKGROUND: Guidelines endorse statin therapy for lowering low-density
      lipoprotein cholesterol (LDL-C) to recommended levels, in patients with
      cardiovascular disease (CVD) risk, if needed, after lifestyle changes.
      Atorvastatin is a common statin with greater LDL-C lowering efficacy than most
      other statins; its availability in generic form will likely increase its use.
      This study assessed attainment of guideline-recommended LDL-C levels in high-risk
      CVD patients treated with atorvastatin monotherapy. METHODS: Analyses of two
      retrospective US cohorts of patients who received a prescription for atorvastatin
      monotherapy between January 1, 2008 and December 31, 2010 (index date defined as
      first prescription date) in the GE Centricity Electronic Medical Record (EMR)
      (N=10,693) and Humana Medicare (N=16,798) databases. Eligible patients were >=18
      years, diagnosed with coronary heart disease or atherosclerotic vascular disease,
      with >=1 LDL-C measurement between 3 months and 1 year postindex date, and
      continuously enrolled for 1 year prior to and following the index date. RESULTS:
      Of the eligible patients, 21.8%, 29.6%, 29.9%, and 18.7% (GE Centricity EMR) and
      25.4%, 32.9%, 27.8%, and 14.0% (Humana Medicare) received 10, 20, 40, and 80 mg
      doses of atorvastatin, respectively. The mean +/- standard deviation (SD) follow
      up LDL-C levels were 2.1+/-0.8 mmol/L (83+/-30 mg/dL) and 2.3+/-0.8 mmol/L (88+/
      31 mg/dL) for the GE Centricity EMR and Humana Medicare cohorts, respectively.
      Regardless of dose, only 28.3%-34.8% of patients had LDL-C levels <1.8 mmol/L
      (<70 mg/dL), and 72.0%-78.0% achieved LDL-C <2.6 mmol/L (<100 mg/dL) in both
      cohorts. As many as 41% and 13% of patients had LDL-C levels >=0.5 mmol/L (>=20
      mg/dL) above LDL-C 1.8 mmol/L (70 mg/dL) and 2.6 mmol/L (100 mg/dL),
      respectively, in both cohorts; these percentages were generally similar across
      atorvastatin doses. CONCLUSION: In this real-world US setting, a large number of
      high-risk CVD patients did not attain guideline-recommended LDL-C levels with
      atorvastatin monotherapy. More than 65% of the patients had LDL-C levels >1.8
      mmol/L (>70 mg/dL), and of these, 30%-40% had LDL-C levels >=0.5 mmol/L (>=20
      mg/dL) above this, regardless of dose. This suggests that more effective lipid
      lowering strategies, such as statin uptitration, switching to a higher efficacy
      statin, and/or combination therapy, may be required to achieve optimal LDL-C
      lowering in high-risk patients.

PMID- 24851052
TI  - Inhibition of hepatic microsomal triglyceride transfer protein - a novel
      therapeutic option for treatment of homozygous familial hypercholesterolemia.
AB  - Familial hypercholesterolemia (FH) is an autosomal dominant disease caused by
      mutations in the low-density lipoprotein (LDL)-receptor gene (LDLR). Patients
      with homozygous FH (hoFH) have inherited a mutated LDLR gene from both parents,
      and therefore all their LDL-receptors are incapable of functioning normally. In
      hoFH, serum LDL levels often exceed 13 mmol/L and tendon and cutaneous xanthomata
      appear early (under 10 years of age). If untreated, this extremely severe form of
      hypercholesterolemia may cause death in childhood or in early adulthood. Based on
      recent data, it can be estimated that the prevalence of hoFH is about 1:500,000
      or even 1:400,000. Until now, the treatment of hoFH has been based on high-dose
      statin treatment combined with LDL apheresis. Since the LDL cholesterol-lowering
      effect of statins is weak in this disease, and apheresis is a cumbersome
      treatment and not available at all centers, alternative novel pharmaceutical
      therapies are needed. Lomitapide is a newly introduced drug, capable of
      effectively decreasing serum LDL cholesterol concentration in hoFH. It inhibits
      the microsomal triglyceride transfer protein (MTTP). By inhibiting in hepatocytes
      the transfer of triglycerides into very low density lipoprotein particles, the
      drug blocks their assembly and secretion into the circulating blood. Since the
      very low density lipoprotein particles are precursors of LDL particles in the
      circulation, the reduced secretion of the former results in lower plasma
      concentration of the latter. The greatest concern in lomitapide treatment has
      been the increase in liver fat, which can be, however, counteracted by strictly
      adhering to a low-fat diet. Lomitapide is a welcome addition to the meager
      selection of drugs currently available for the treatment of refractory
      hypercholesterolemia in hoFH patients. 

PMID- 24851053
TI  - Influence of serological factors and BMI on the blood pressure/hematocrit
      association in healthy young men and women.
AB  - The association between mean arterial blood pressure (MAP) and hematocrit (Hct)
      as a surrogate for blood viscosity was investigated in a young (average 20.0+/
      2.3 years), healthy population of 174 men and 442 women. Health status was
      assessed by clinical examination and serological evaluation. Individuals with
      severe anemia or hemoconcentration, prior traumas or major surgical intervention,
      smokers, and pregnant or lactating women were excluded from the study. The
      MAP/Hct association was positive and significant (P=0.04) for women and negative,
      albeit not significantly so, for men. The MAP/Hct association was also evaluated
      in subgroups of the same population with a progressive step-by-step exclusion of:
      individuals with cholesterol >200 mg/dL; triglycerides >200 mg/dL; body mass
      index >25 kg/m(2); and glucose >100 mg/dL. This consecutively reduced the
      strength of the positive MAP/Hct association in women, which became negative -
      although not significantly so - when all anomalously high factors were excluded.
      The same trend was found in men. Our study indicates that previously reported
      positive trends in the relationship between the MAP and Hct in the population are
      not present in a young, healthy population of men or women that excludes
      individuals with the confounding factors of above normal serological values and
      BMI. 

PMID- 24851054
TI  - Primary small-cell neuroendocrine carcinoma of the male breast: a rare case
      report with review of the literature.
AB  - In this case study and review, we present a case of a primary small-cell
      neuroendocrine carcinoma (SCNC) of the male breast. Primary SCNC of the breast is
      a rare tumor with less than 30 cases reported in the literature. Most cases are
      found in women. Another exceptional point is that human epidermal growth factor
      receptor-2 (Her-2) immunoreactivity was positive in our recent case, which
      differed to previous reports detailing SCNC in women. We have no evidence to
      demonstrate the differences between treatment and prognoses for males and
      females, because we do not have sufficient cases to undertake an evidence-based
      investigation. We provide this rare case history; review the literature on SCNC
      of the breast; and discuss detailed information regarding epidemiology,
      histogenesis, clinical and histologic diagnosis criteria, surgical and adjuvant
      treatment, and prognosis. 

PMID- 24851055
TI  - Differential serum protein markers and the clinical severity of asthma.
AB  - BACKGROUND: Asthma is a heterogeneous disease characterized by different clinical
      phenotypes and the involvement of multiple inflammatory pathways. During airway
      inflammation, many cytokines and chemokines are released and some are detectable
      in the sera. OBJECTIVE: Serum chemokines and cytokines, involved in airway
      inflammation in asthma patients, were investigated. METHODS: A total of 191
      asthma patients were classified by hierarchical cluster analysis, including the
      following parameters: forced expiratory volume in 1 second (FEV1), eosinophil
      cationic protein (ECP) serum levels, blood eosinophils, Junipers asthma symptom
      score, and the change in FEV1, ECP serum levels, and blood eosinophils after 3
      weeks of asthma therapy. Serum proteins were measured by multiplex analysis.
      Receiver operating characteristic (ROC) curves were used to evaluate the validity
      of serum proteins for discriminating between asthma clusters. RESULTS:
      Classification of asthma patients identified one cluster with high ECP serum
      levels, increased blood eosinophils, low FEV1 values, and good FEV1 improvement
      in response to asthma therapy (n=60) and one cluster with low ECP serum levels,
      low numbers of blood eosinophils, higher FEV1 values, and no FEV1 improvement in
      response to asthma therapy (n=131). Serum interleukin (IL)-8, eotaxin, vascular
      endothelial growth factor (VEGF), cutaneous T-cell-attracting chemokine (CTACK),
      growth-related oncogene (GRO)-alpha, and hepatocyte growth factor (HGF) were
      significantly different between the two clusters of asthma patients. ROC analysis
      for serum proteins calculated a sensitivity of 55.9% and specificity of 75.8% for
      discriminating between them. CONCLUSION: Serum cytokine and chemokine levels
      might be predictors for the severity of asthmatic inflammation, asthma control,
      and response to therapy, and therefore might be useful for treatment
      optimization.

PMID- 24851056
TI  - From Catastrophizing to Recovery: a pilot study of a single-session treatment for
      pain catastrophizing.
AB  - BACKGROUND: Pain catastrophizing (PC) - a pattern of negative cognitive-emotional
      responses to real or anticipated pain - maintains chronic pain and undermines
      medical treatments. Standard PC treatment involves multiple sessions of cognitive
      behavioral therapy. To provide efficient treatment, we developed a single
      session, 2-hour class that solely treats PC entitled "From Catastrophizing to
      Recovery" [FCR]. OBJECTIVES: To determine 1) feasibility of FCR; 2) participant
      ratings for acceptability, understandability, satisfaction, and likelihood to use
      the information learned; and 3) preliminary efficacy of FCR for reducing PC.
      DESIGN AND METHODS: Uncontrolled prospective pilot trial with a retrospective
      chart and database review component. Seventy-six patients receiving care at an
      outpatient pain clinic (the Stanford Pain Management Center) attended the class
      as free treatment and 70 attendees completed and returned an anonymous survey
      immediately post-class. The Pain Catastrophizing Scale (PCS) was administered at
      class check-in (baseline) and at 2, and 4 weeks post-treatment. Within subjects
      repeated measures analysis of variance (ANOVA) with Student's t-test contrasts
      were used to compare scores across time points. RESULTS: All attendees who
      completed a baseline PCS were included as study participants (N=57; F=82%; mean
      age =50.2 years); PCS was completed by 46 participants at week 2 and 35
      participants at week 4. Participants had significantly reduced PC at both time
      points (P<0001) and large effect sizes were found (Cohen's d=0.85 and d=1.15).
      CONCLUSION: Preliminary data suggest that FCR is an acceptable and effective
      treatment for PC. Larger, controlled studies of longer duration are needed to
      determine durability of response, factors contributing to response, and the
      impact on pain, function and quality of life.

PMID- 24851057
TI  - Fear, guilt, and debt: an exploration of women's experience and perception of
      cesarean birth in Burkina Faso, West Africa.
AB  - BACKGROUND: This paper explores women's experience and perception of cesarean
      birth in Burkina Faso and its social and economic implications within the
      household. METHODS: Five focus groups comprising mothers or pregnant women were
      conducted among residents of Bogodogo Health District in Ouagadougou to assess
      the perceptions of cesarean section (CS) by women in the community. In addition,
      35 individual semistructured interviews were held at the homes of women who had
      just undergone CS in the referral hospital, and were conducted by an
      anthropologist and a midwife. RESULTS: Home visits to women with CS identified
      common fears about the procedure, such as "once you have had a CS, you will
      always have to deliver by CS". The central and recurring theme in the interviews
      was communication between patients and care providers, ie, women were often not
      informed of the imminence of CS in the delivery room. Information given by health
      care professionals was often either not explicit enough or not understood. The
      women received insufficient information about postoperative personal hygiene,
      diet, resumption of sexual activity, and contraception. Overall, analysis of the
      experiences of women who had undergone CS highlighted feelings of guilt in the
      aftermath of CS. Other concerns included the feeling of not being a "good mother"
      who can give birth normally, alongside concerns about needing a CS in future
      pregnancies, the high costs that this might incur for their households, general
      fatigue, and possible medical complications after surgery. CONCLUSION: Poor
      quality of care and the economic burden of CS place women in a multifaceted
      situation of vulnerability within the family. CS has a medical, emotional,
      social, and economic impact on poor African women that cannot be ignored.
      Managers of maternal health programs need to understand women's perceptions of CS
      so as to overcome existing barriers to this life-saving procedure.

PMID- 24851058
TI  - MRI-conditional pacemakers: current perspectives.
AB  - Use of both magnetic resonance imaging (MRI) and pacing devices has undergone
      remarkable growth in recent years, and it is estimated that the majority of
      patients with pacemakers will need an MRI during their lifetime. These
      investigations will generally be denied due to the potentially dangerous
      interactions between cardiac devices and the magnetic fields and radio frequency
      energy used in MRI. Despite the increasing reports of uneventful scanning in
      selected patients with conventional pacemakers under close surveillance, MRI is
      still contraindicated in those circumstances and cannot be considered a routine
      procedure. These limitations prompted a series of modifications in generator and
      lead engineering, designed to minimize interactions that could compromise device
      function and patient safety. The resulting MRI-conditional pacemakers were first
      introduced in 2008 and the clinical experience gathered so far supports their
      safety in the MRI environment if certain conditions are fulfilled. With this
      technology, new questions and controversies arise regarding patient selection,
      clinical impact, and cost-effectiveness. In this review, we discuss the potential
      risks of MRI in patients with electronic cardiac devices and present updated
      information regarding the features of MRI-conditional pacemakers and the clinical
      experience with currently available models. Finally, we provide some guidance on
      how to scan patients who have these devices and discuss future directions in the
      field. 

PMID- 24851059
TI  - Minimally invasive arthrodesis for chronic sacroiliac joint dysfunction using the
      SImmetry SI Joint Fusion system.
AB  - Chronic sacroiliac (SI) joint-related low back pain (LBP) is a common, yet under
      diagnosed and undertreated condition due to difficulties in accurate diagnosis
      and highly variable treatment practices. In patients with debilitating SI-related
      LBP for at least 6 months duration who have failed conservative management,
      arthrodesis is a viable option. The SImmetry((r)) SI Joint Fusion System is a
      novel therapy for SI joint fusion, not just fixation, which utilizes a minimally
      invasive surgical approach, instrumented fixation for immediate stability, and
      joint preparation with bone grafting for a secure construct in the long term. The
      purpose of this report is to describe the minimally invasive SI Joint Fusion
      System, including patient selection criteria, implant characteristics, surgical
      technique, postoperative recovery, and biomechanical testing results. Advantages
      and limitations of this system will be discussed. 

PMID- 24851061
TI  - The renin-angiotensin system and aging in the kidney.
AB  - Aging is associated with progressive functional deterioration and structural
      changes in the kidney. Changes in the activity or responsiveness of the renin
      angiotensin system (RAS) occur with aging. RAS changes predispose the elderly to
      various fluid and electrolyte imbalances as well as acute kidney injury and
      chronic kidney disease. Among the multiple pathways involved in renal aging, the
      RAS plays a central role. This review summarizes the association of the RAS with
      structural and functional changes in the aging kidney and age-related renal
      injury, and describes the underlying mechanisms of RAS-related renal aging. An
      improved understanding of the renal aging process may lead to better
      individualized care of the elderly and improved renal survival in age-related
      diseases. 

PMID- 24851060
TI  - Modifiers of TGF-beta1 effector function as novel therapeutic targets of
      pulmonary fibrosis.
AB  - Pulmonary fibrosis is a fatal progressive disease with no effective therapy.
      Transforming growth factor (TGF)-beta1 has long been regarded as a central
      mediator of tissue fibrosis that involves multiple organs including skin, liver,
      kidney, and lung. Thus, TGF-beta1 and its signaling pathways have been attractive
      therapeutic targets for the development of antifibrotic drugs. However, the
      essential biological functions of TGF-beta1 in maintaining normal immune and
      cellular homeostasis significantly limit the effectiveness of TGF-beta1-directed
      therapeutic approaches. Thus, targeting downstream mediators or signaling
      molecules of TGF-beta1 could be an alternative approach that selectively inhibits
      TGF-beta1-stimulated fibrotic tissue response while preserving major
      physiological function of TGF-beta1. Recent studies from our laboratory revealed
      that TGF-beta1 crosstalk with epidermal growth factor receptor (EGFR) signaling
      by induction of amphiregulin, a ligand of EGFR, plays a critical role in the
      development or progression of pulmonary fibrosis. In addition, chitotriosidase, a
      true chitinase in humans, has been identified to have modulating capacity of TGF
      beta1 signaling as a new biomarker and therapeutic target of scleroderma
      associated pulmonary fibrosis. These newly identified modifiers of TGF-beta1
      effector function significantly enhance the effectiveness and flexibility in
      targeting pulmonary fibrosis in which TGF-beta1 plays a significant role. 

PMID- 24851062
TI  - A disappearing vertical infection: will hepatitis B be a forgotten disease in
      children?

PMID- 24851064
TI  - Clinical implications of follicular and Hurthle cell carcinoma in an iodine
      sufficient area.

PMID- 24851063
TI  - Is amlodipine more cardioprotective than other antihypertensive drug classes?

PMID- 24851065
TI  - Survey of perinatal hepatitis B virus transmission after Korean National
      Prevention Program in a tertiary hospital.
AB  - BACKGROUND/AIMS: The Ministry of Health and Welfare and the Korea Centers for
      Disease Control and Prevention in South Korea have been organizing hepatitis B
      virus (HBV) vertical infection prevention projects since July 2002. In this
      single-institute study, the results of surveys conducted in target mothers who
      delivered babies in a tertiary hospital were investigated and analyzed. METHODS:
      Of the 9,281 mothers and their 9,824 neonates born between July 2002 and December
      2012, 308 hepatitis B surface antigen (HBsAg)-positive mothers and their 319
      neonates were selected for this study, and their records were analyzed
      retrospectively. RESULTS: A total of 308 mothers were HBsAg-positive, with an HBV
      prevalence of 3.32% (308/9,281). There were 319 neonates born to these HBsAg
      positive mothers, and 252 were confirmed to as either HBsAg-positive or 
      negative. Four were confirmed as HBsAg-positive, with a 1.59% (4/252) HBV
      vertical infection rate. All the mothers of neonates who had an HBV vertical
      infection were hepatitis B e antigen (HBeAg)-positive. Among the HBsAg-positive
      neonates, three were HBeAg-positive and had an HBV DNA titer of 1.0 * 10(8)
      copies/mL. CONCLUSIONS: The HBV prevalence of mothers was 3.32% (308/9,281), and
      their vertical infection rate was 1.59% (4/252). Thus, the South Korean HBV
      vertical infection prevention projects are effective, and, accordingly, HBV
      prevalence in South Korea is expected to decrease continuously.

PMID- 24851066
TI  - Amlodipine and cardiovascular outcomes in hypertensive patients: meta-analysis
      comparing amlodipine-based versus other antihypertensive therapy.
AB  - BACKGROUND/AIMS: This meta-analysis compared the effects of amlodipine besylate,
      a charged dihydropyridine-type calcium channel blocker (CCB), with other non-CCB
      antihypertensive therapies regarding the cardiovascular outcome. METHODS: Data
      from seven long-term outcome trials comparing the cardiovascular outcomes of an
      amlodipine-based regimen with other active regimens were pooled and analyzed.
      RESULTS: The risk of myocardial infarction was significantly decreased with an
      amlodipine-based regimen compared with a non-CCB-based regimen (odds ratio [OR],
      0.91; 95% confidence interval [CI], 0.84 to 0.99; p = 0.03). The risk of stroke
      was also significantly decreased (OR, 0.84; 95% CI, 0.79 to 0.90; p < 0.00001).
      The risk of heart failure increased slightly with marginal significance for an
      amlodipine-based regimen compared with a non-CCB-based regimen (OR, 1.14; 95% CI,
      0.98 to 1.31; p = 0.08). However, when compared overall with beta-blockers and
      diuretics, amlodipine showed a comparable risk. Amlodipine-based regimens
      demonstrated a 10% risk reduction in overall cardiovascular events (OR, 0.90; 95%
      CI, 0.82 to 0.99; p = 0.02) and total mortality (OR, 0.95; 95% CI, 0.91 to 0.99;
      p = 0.01). CONCLUSIONS: Amlodipine reduced the risk of total cardiovascular
      events as well as all-cause mortality compared with non-CCB-based regimens,
      indicating its benefit for high-risk cardiac patients.

PMID- 24851067
TI  - Follicular and Hurthle cell carcinoma of the thyroid in iodine-sufficient area:
      retrospective analysis of Korean multicenter data.
AB  - BACKGROUND/AIMS: Follicular thyroid carcinoma (FTC) and Hurthle cell carcinoma
      (HCC) of the thyroid are relatively uncommon thyroid malignancies in iodine
      sufficient areas. In this study we evaluated the clinical behavior, prognostic
      factors and treatment outcomes of FTC and HCC in Korea. METHODS: This multicenter
      study included 483 patients with FTC and 80 patients with HCC who underwent an
      initial surgery between 1995 and 2006 in one of the four tertiary referral
      hospitals in Korea. We evaluated clinicopathological factors associated with
      distant metastases and recurrence during a median of 6 years of follow-up.
      RESULTS: HCC patients were significantly older (49 years vs. 43 years; p < 0.001)
      and had more lymphovascular invasions (22% vs. 14%; p = 0.03) compared with FTC
      patients. Distant metastases were confirmed in 40 patients (8%) in the FTC group
      and in two patients (3%) in the HCC group (p = 0.07). Distant metastases were
      significantly associated with older age, widely invasive cancer and
      extrathyroidal invasion. Only 14 patients (3%) had recurrent disease and there
      was no significant difference between FTC and HCC groups (p = 0.38). Recurrence
      was associated with larger tumor size and cervical lymph node metastasis.
      CONCLUSIONS: HCC patients were older and had more lymphovascular invasions than
      FTC patients. However, FTC and HCC patients had similar initial
      clinicopathological features. Older age, wide invasiveness and extrathyroidal
      invasion were independent risk factors for predicting distant metastases in FTC
      and HCC patients.

PMID- 24851068
TI  - Urinary excretion of beta2-microglobulin as a prognostic marker in immunoglobulin
      A nephropathy.
AB  - BACKGROUND/AIMS: beta2-microglobulin (beta2-MG) is freely filtered at the
      glomerulus and subsequently reabsorbed and catabolized by proximal renal tubular
      cells. Urinary beta2-MG is an early and sensitive biomarker of acute kidney
      injury; however, its utility as a biomarker of immunoglobulin A nephropathy
      (IgAN) is unclear. METHODS: We included urinary beta2-MG levels in the routine
      laboratory examination of all inpatients with biopsy-proven IgAN at our hospital
      from 2006 to 2010. We retrospectively analyzed the correlation between beta2-MG
      levels and clinical parameters as a prognostic biomarker of IgAN. RESULTS: A
      total of 51 patients (30 males, 21 females; mean age, 33.01 +/- 12.73 years) with
      IgAN were included in this study. Initial demographic, clinical, and laboratory
      data for all patients are listed. The mean initial estimated glomerular
      filtration rate and 24-hour urine protein levels were 94.69 +/- 34.78 mL/min/1.73
      m(2) and 1.28 +/- 1.75 g/day, respectively. The mean level of urinary beta2-MG
      was 1.92 +/- 7.38 ug/mg creatinine. There was a significant correlation between
      initial serum creatinine (iSCr), urine protein creatinine ratio (UPCR), and the
      level of beta2-MG (r = 0.744, r = 0.667, p < 0.01). There was also a significant
      correlation between renal function tests and the level of urinary beta2-MG (p <
      0.01). Cox regression analysis showed that albumin, beta2-MG, iSCr, and UPCR were
      significant predictors of disease progression in IgAN. CONCLUSIONS: Urinary beta2
      MG levels showed a significant correlation with renal function and proteinuria in
      IgAN. Thus, we propose that urinary beta2-MG may be an additional prognostic
      factor in patients with IgAN.

PMID- 24851069
TI  - A mild decrease of renal function is related to increased hemoglobin level during
      5-year follow-up period.
AB  - BACKGROUND/AIMS: We analyzed chronological changes in hemoglobin according to
      renal function changes over a 5-year follow-up period. METHODS: We enrolled 5,266
      adults with a glomerular filtration rate (GFR) >= 60 mL/min/1.73 m(2) at an
      initial examination at a routine health check-up; a follow-up examination was
      conducted 5 years later. We categorized the subjects according to GFR ratio
      (groups 1, 2, and 3, defined as GFRratio >= 1.00, 0.75 to 0.99, and < 0.75,
      respectively). RESULTS: The mean hemoglobin level in subjects with a GFR of 60 to
      74 was higher than in those with a GFR of 75 to 89 or >= 90 mL/min/1.73 m(2) at
      the initial examination (all p < 0.001). Among females and males, the frequencies
      of increased hemoglobin were 46.8% and 40.6% in the GFRratio group 1, 52.4% and
      46.1% in group 2, and 59.6% and 52.5% in group 3 over the 5-year period,
      respectively (all p < 0.001). With multiple logistic regression, group 3 showed
      1.594-fold (95% confidence interval [CI], 1.127 to 2.225) and 1.353-fold (95% CI,
      1.000 to 1.830) higher likelihoods of increased hemoglobin over the 5-year follow
      up period in females and males, respectively. The estimated difference in
      hemoglobin level was highest in group 3 in both genders. These findings were more
      evident in subgroups without metabolic syndrome, diabetes mellitus, hypertension,
      or GFR less than 90 mL/min/1.73 m(2). CONCLUSIONS: Among a population with GFR >=
      60 mL/min/1.73 m(2), a mild decrease in GFR over a 5-year follow-up period was
      associated with an increase in hemoglobin levels.

PMID- 24851070
TI  - Clinical characteristics, pathological distribution, and prognostic factors in
      non-Hodgkin lymphoma of Waldeyer's ring: nationwide Korean study.
AB  - BACKGROUND/AIMS: In Asia, the incidence of non-Hodgkin lymphoma (NHL) has
      increased in recent decades. Waldeyer's ring (WR) is the most common site of NHL
      involving the head and neck. In this study, the pathological distribution of WR
      NHL and its clinical features were analyzed retrospectively. METHODS: From
      January 2000 through December 2010, we analyzed the medical records of 328
      patients from nine Korean institutions who were diagnosed with WR-NHL. RESULTS:
      The study group comprised 197 male and 131 female patients with a median age of
      58 years (range, 14 to 89). The rate of localized disease (stage I/II) was 64.9%,
      and that of low-risk disease (low/low-intermediate, as defined by the
      International Prognostic Index) was 76.8%. Diffuse large B-cell lymphoma (DLBCL;
      240 patients, 73.2%) was the most common pathologic subtype, followed by
      peripheral T-cell lymphoma (14 patients, 4.3%) and nasal NK/T-cell lymphoma (14
      patients, 4.3%). WR-NHL occurred most frequently in the tonsils (199 patients,
      60.6%). Extranodal involvement was greater with the T-cell subtype (20 patients,
      42.5%) compared with the B-cell subtype (69 patients, 24.5%). Multivariate
      analyses showed that age >= 62 years, T-cell subtype, and failure to achieve
      complete remission were significant risk factors for overall survival.
      CONCLUSIONS: DLBCL was found to have a higher incidence in Korea than those
      incidences reported by other WR-NHL studies. T-cell lymphoma occurred more
      frequently than did follicular lymphoma. T-cell subtype, age >= 62 years, and
      complete remission failure after first-line treatment were significant poor
      prognostic factors for overall survival according to the multivariate analysis.

PMID- 24851071
TI  - Clinical factors and treatment outcomes associated with failure in the detection
      of urate crystal in patients with acute gouty arthritis.
AB  - BACKGROUND/AIMS: To investigate the rate of detection of monosodium urate (MSU)
      crystals in the synovial fluid (SF) of patients with acute gouty arthritis and
      factors associated with false-negative results. METHODS: A total of 179 patients
      with acute gouty arthritis who had undergone SF crystal examination were
      identified from the data warehouse of two university hospitals. Clinical and
      laboratory data were obtained from the medical records. RESULTS: The overall rate
      of detection of MSU crystals was 78.8%. In univariate analyses, the only
      significant differences between the variables of crystal-negative and crystal
      positive patients were a lower C-reactive protein level (p = 0.040) and fewer
      patients undergoing emergent surgery in the crystal-positive group (p = 4.5 * 10(
      6)). In logistic regression analyses, MSU crystal-negative results were
      significantly associated with the interval from arthritis onset to crystal
      examination (p = 0.042), and this was the most significant risk factor for
      arthroscopic surgery (p = 2.1 * 10(-4)). Seventeen patients who underwent
      arthroscopic surgery had a significantly longer hospital stay (p = 0.007) and a
      significant delay in gout treatment (p = 8.74 * 10(-5)). The distribution of
      crystal-negative patients differed significantly between the SF samples that were
      evaluated by both the laboratory medicine and the rheumatology departments (p =
      1.2 * 10(-14)), and the kappa value was 0.108. CONCLUSIONS: Although several
      clinical features were associated with detection failure, SF MSU crystal
      identification was critically dependent on the observer. Considering the impact
      on the treatment outcomes, implementation of a quality control program is
      essential.

PMID- 24851072
TI  - Cryptococcal meningitis in a patient with chronic hepatitis C treated with
      pegylated-interferon and ribavirin.
AB  - Various adverse events have been reported during combination therapy with
      pegylated (PEG)-interferon-alpha and ribavirin, although opportunistic
      infections, especially cryptococcal meningitis, are very rare. A 61-year-old
      woman complained of headaches and a fever during treatment of a chronic hepatitis
      C virus (HCV) infection. She had been treated for 7 months. Her headaches were
      refractory to analgesics, and she developed subtle nuchal rigidity. The cerebral
      spinal fluid (CSF) revealed a white blood cell count of 205/mm(3), 51 mg/dL
      protein, 35 mg/dL glucose, and negative Cryptococcus antigen. The CSF culture
      resulted in no growth. Five days later, the CSF was positive for Cryptococcus
      antigen. We administered amphotericin B and flucytosine, followed by fluconazole.
      Approximately 2 months later, she was discharged. For the first time, we report a
      case of cryptococcal meningitis during the treatment of chronic HCV with PEG
      interferon-alpha and ribavirin. 

PMID- 24851073
TI  - A case of ampullary gangliocytic paraganglioma.
AB  - Gangliocytic paragangliomas (GPs) are rare tumors of the duodenum, presenting as
      single sessile or pedunculated polypoid masses. Clinical manifestations of
      duodenal GPs can vary from an incidental finding at endoscopy to frequent upper
      gastrointestinal bleeding caused by mucosal ulceration and abdominal pain. GPs
      are considered benign, but the disease can recur and spread to regional lymph
      nodes. A 41-year-old female presented with abdominal pain. Upper gastrointestinal
      endoscopy revealed a subepithelial tumor of the ampulla of Vater in the second
      portion of the duodenum. The tumor was resected using the endoscopic mucosal
      resection technique. The tumor was diagnosed as benign GP of the duodenum using
      histological and immunohistochemical staining procedures. 

PMID- 24851074
TI  - Acute esophageal necrosis occurring in a patient undergoing percutaneous coronary
      intervention.
AB  - Acute esophageal necrosis is uncommon in the literature. Its etiology is unknown,
      although cardiovascular disease, hemodynamic compromise, gastric outlet
      obstruction, alcohol ingestion, hypoxemia, hypercoagulable state, infection, and
      trauma have all been suggested as possible causes. A 67-year-old female underwent
      a coronary angiography (CAG) for evaluation of chest pain. CAG findings showed
      coronary three-vessel disease. We planned percutaneous coronary intervention
      (PCI). Coronary arterial dissection during the PCI led to sudden hypotension. Six
      hours after the index procedure, the patient experienced a large amount of
      hematemesis. Emergency gastrofibroscopy was performed and showed mucosal necrosis
      with a huge adherent blood clot in the esophagus. After conservative treatment
      for 3 months, the esophageal lesion was completely improved. She was diagnosed
      with acute esophageal necrosis. We report herein a case of acute esophageal
      necrosis occurring in a patient undergoing percutaneous coronary intervention. 

PMID- 24851075
TI  - Distant subcutaneous recurrence of a parathyroid carcinoma: abnormal uptakes in
      the (99m)Tc-sestamibi scan and (18)F-FDG PET/CT imaging.
AB  - We report a rare case of distant subcutaneous parathyroid carcinoma recurrence. A
      50-year-old woman was referred to our hospital because of sustained hypercalcemia
      despite surgical removal of a parathyroid carcinoma. A focal uptake in the upper
      mediastinal area was detected in a (99m)Tc-sestamibi scan, and (18)F
      fluorodeoxyglucose (FDG) positron-emission tomography (PET)/computed tomography
      (CT) imaging demonstrated a subcutaneous mass. She underwent tumor resection, and
      the pathological findings were consistent with a parathyroid carcinoma. The
      postoperative serum parathyroid hormone (PTH) level remained within normal
      limits. However, a new palpable solitary mass was identified in the upper portion
      of the left breast 1 year postoperatively. Both a (99m)Tc-sestamibi scan and
      (18)F-FDG PET/CT imaging revealed an abnormal lesion in the upper breast, and
      subsequent pathology reports confirmed parathyroid carcinoma metastasis. Serum
      PTH and calcium levels fell within normal ranges after tumor resection. Two
      subcutaneous recurrent lesions appeared likely due to tumor seeding during the
      previous endoscopic operation at a local hospital. 

PMID- 24851076
TI  - Unsupported conclusions in the article "Synephrine-containing dietary supplement
      precipitating apical ballooning syndrome in a young female".

PMID- 24851077
TI  - A case of Wegener's granulomatosis mimicking recurrent hemophagocytic
      lymphohistiocytosis.

PMID- 24851078
TI  - Native valve endocarditis due to extended spectrum beta-lactamase producing
      Klebsiella pneumoniae.

PMID- 24851079
TI  - Unusual metatarsophalangeal joint deformity in an advanced rheumatoid foot.

PMID- 24851080
TI  - Detection of calcium pyrophosphate dihydrate crystal deposition disease by dual
      energy computed tomography.

PMID- 24851081
TI  - Unusual cause of back pain in a 13-year-old boy: a thoracic osteoblastoma.

PMID- 24851082
TI  - Design, synthesis and characterization of a modular bridging ligand platform for
      bio-inspired hydrogen production.
AB  - Synthesis and characterization of a novel type of ambident bridging ligands
      joining together the functional prerequisites for visible-light absorption,
      photoinduced electron transfer and catalytic proton reduction is presented. This
      class of compounds consists of a chromophoric 1,2-diimine-based pi-acceptor site
      and a rigid polyaromatic dithiolate chelator. Due to the presence of a common
      conjugated linker moiety with an intrinsic two-electron redox reactivity and a
      suitable orbital coupling of the subunits, a favourable situation for vectorial
      multielectron transfer from attached electron donors to a catalytic acceptor site
      is provided. As an example for the application of this kind of bifunctional
      ligand systems, a [FeFe]-hydrogenase enzyme model compound is prepared and
      structurally characterized. Electrocatalytic hydrogen formation with this complex
      is demonstrated.

PMID- 24851083
TI  - Chorioamnionitis (ChA) modifies CX3CL1 (fractalkine) production by human amniotic
      epithelial cells (HAEC) under normoxic and hypoxic conditions.
AB  - BACKGROUND: Chemokine CX3CL1 possesses unique properties, including combined
      adhesive and chemotactic functions. Human amniotic epithelial cells (HAEC) show
      expression of CX3CL1 receptor (CX3CR1) and produce CX3CL1 in response to both
      physiologic and pathologic stimuli. Chorioamnionitis (ChA) is a common
      complication of pregnancy and labour. ChA is often accompanied by local hypoxia
      because of the high oxygen consumption at the site of inflammation. We examined
      comparatively (ChA-complicated vs. normal pregnancy) CX3CR1 expression and the
      effects of hypoxia, lipopolysaccharide (LPS), and CX3CR1 blockade on CX3CL1
      production in HAEC cultured in vitro. METHODS: HAEC have been isolated using
      trypsinization, and cultured under normoxia (20% O2) vs. hypoxia (5% O2).
      According to the experimental design, LPS (1 MUg/ml) and neutralizing anti-CX3CR1
      antibodies were added at respective time points. Mean CX3CL1 concentration in the
      supernatant samples were determined by ELISA. Expression of immunostained CX3CR1
      was analyzed using quantitative morphometry. RESULTS: We have found that the mean
      levels of CX3CL1 and CX3CR1 expression were remarkably (p < 0.05) higher in ChA,
      compared to normal pregnancy. Significantly increased expression of CX3CR1 was
      observed in ChA during both normoxia and hypoxia. Hypoxia exposure produced
      decrease in the mean concentration of CX3CL1 in both groups, however this
      reduction was stronger in normal pregnancy. In normoxia, LPS-evoked rise in the
      mean concentration of CX3CL1 was higher (p < 0.05) in normal pregnancy. This
      response was positively correlated with CX3CR1 expression. Blockade of CX3CR1
      canceled the secretory response to LPS in all groups. CONCLUSIONS: ChA
      complicated pregnancy up-regulates CX3CR1 in HAEC cultured in vitro with
      simultaneous increase in CX3CL1 production. Hypoxia-resistant production of
      CX3CL1 may be responsible for ChA-related complications of pregnancy and labor.

PMID- 24851085
TI  - Cooperative quantum-behaved particle swarm optimization with dynamic varying
      search areas and Levy flight disturbance.
AB  - This paper proposes a novel variant of cooperative quantum-behaved particle swarm
      optimization (CQPSO) algorithm with two mechanisms to reduce the search space and
      avoid the stagnation, called CQPSO-DVSA-LFD. One mechanism is called Dynamic
      Varying Search Area (DVSA), which takes charge of limiting the ranges of
      particles' activity into a reduced area. On the other hand, in order to escape
      the local optima, Levy flights are used to generate the stochastic disturbance in
      the movement of particles. To test the performance of CQPSO-DVSA-LFD, numerical
      experiments are conducted to compare the proposed algorithm with different
      variants of PSO. According to the experimental results, the proposed method
      performs better than other variants of PSO on both benchmark test functions and
      the combinatorial optimization issue, that is, the job-shop scheduling problem. 

PMID- 24851084
TI  - Forced expression of S100A10 reduces sensitivity to oxaliplatin in colorectal
      cancer cells.
AB  - BACKGROUND: Individual responses to oxaliplatin (L-OHP)-based chemotherapy remain
      unpredictable. Our recent proteomics studies have demonstrated that intracellular
      protein expression levels of S100A10 are significantly correlated with the
      sensitivity of colorectal cancer (CRC) cells to L-OHP, but not 5-FU, suggesting
      that S100A10 is a candidate predictive marker for the response to L-OHP. In this
      study, we investigated whether S100A10 is involved in L-OHP sensitivity or not.
      RESULTS: Forced expression of S100A10 in COLO-320 CRC cells significantly
      increased the 50% inhibitory concentration (IC50) for L-OHP (P = 0.003), but did
      not change that for 5-FU, indicating that S100A10 is more specific to L-OHP than
      5-FU. Silencing of the S100A10 gene showed no apparent effect on sensitivity to L
      OHP in HT29 cells. Silencing of the annexin A2 (a binding partner of S100A10)
      gene alone downregulated both annexin A2 and S100A10 protein levels, with no
      change in S100A10 gene expression. However, original levels of intact S100A10
      protein in CRC cells positively correlated with S100A10 mRNA levels (P = 0.002, R
      = 0.91). CONCLUSIONS: The present results have shown that protein expression of
      S100A10 was associated with resistance to L-OHP, but not 5-FU, supporting the
      hypothesis that S100A10 expression may predict L-OHP sensitivity. Thus, our
      present study provides basic findings to support that S100A10 expression can be
      used as a predictive marker for tumor sensitivity to L-OHP.

PMID- 24851086
TI  - Protein Kinase C-Related Kinase (PKN/PRK). Potential Key-Role for PKN1 in
      Protection of Hypoxic Neurons.
AB  - Serine/threonine protein kinase C-related kinase (PKN/PRK) is a family of three
      isoenzymes (PKN1, PKN2, PKN3), which are widely distributed in eukaryotic
      organisms and share the same overall domain structure. The Nterminal region
      encompasses a conserved repeated domain, termed HR1a-c as well as a HR2/C2
      domain. The serine/threonine kinase domain is found in the C-terminal region of
      the protein and shows high sequence homology to other members of the PKC
      superfamily. In neurons, PKN1 is the most abundant isoform and has been
      implicated in a variety of functions including cytoskeletal organization and
      neuronal differentiation and its deregulation may contribute to neuropathological
      processes such as amyotrophic lateral sclerosis and Alzheimer's disease. We have
      recently identified a candidate role of PKN1 in the regulation of neuroprotective
      processes during hypoxic stress. Our key findings were that: 1) the activity of
      PKN1 was significantly increased by hypoxia (1% O2) and neurotrophins (nerve
      growth factor and purine nucleosides); 2) Neuronal cells, deficient of PKN1
      showed a decrease of cell viability and neurite formation along with a
      disturbance of the F-actinassociated cytoskeleton; 3) Purine nucleoside-mediated
      neuroprotection during hypoxia was severely hampered in PKN1 deficient neuronal
      cells, altogether suggesting a potentially critical role of PKN1 in
      neuroprotective processes. This review gives an up-to-date overview of the PKN
      family with a special focus on the neuroprotective role of PKN1 in hypoxia. 

PMID- 24851088
TI  - Multi-Target Directed Drugs: A Modern Approach for Design of New Drugs for the
      treatment of Alzheimer's Disease.
AB  - Alzheimer's disease (AD) is a complex neurodegenerative disorder with a multi
      faceted pathogenesis. So far, the therapeutic paradigm "one-compound-one-target"
      has failed and despite enormous efforts to elucidate the pathophysiology of AD,
      the disease is still incurable. The multiple factors involved in AD include
      amyloid aggregation to form insoluble neurotoxic plaques of Abeta,
      hyperphosphorylation of tau protein, oxidative stress, calcium imbalance,
      mitochondrial dysfunction and deterioration of synaptic transmission. These
      factors together, accentuate changes in the CNS homeostasis, starting a complex
      process of interconnected physiological damage, leading to cognitive and memory
      impairment and neuronal death. A recent approach for the rational design of new
      drug candidates, also called multitarget-directed ligand (MTDL) approach, has
      gained increasing attention by many research groups, which have developed a
      variety of hybrid compounds acting simultaneously on diverse biological targets.
      This review aims to show some recent advances and examples of the exploitation of
      MTDL approach in the rational design of novel drug candidate prototypes for the
      treatment of AD. 

PMID- 24851089
TI  - The effectiveness of dimethyl fumarate monotherapy in the treatment of relapsing
      remitting multiple sclerosis: a systematic review and meta-analysis.
AB  - BACKGROUND: Dimethyl fumarate (BG-12, Tecfidera(r)) is a new oral drug approved
      by FDA and EMA in March 2013 for relapsing - remitting multiple sclerosis (RRMS).
      The drug was much anticipated because of its possible superiority over currently
      available medications: fingolimod and teriflunomide as the only MS treatments
      currently available in oral form. OBJECTIVE: The aim of this systematic review
      with meta-analysis was to assess the efficacy and safety of BG-12 in the
      treatment of RRMS. METHODS: A systematic literature search was conducted in
      Medline/PubMed, EMBASE, and Cochrane Library up till 3(rd) November, 2013. We
      sought all published randomized clinical trials evaluating the use of dimethyl
      fumarate for the treatment of patients with RRMS. All included studies were
      critically appraised and analyzed with the use of Review Manager 5.1.0. software
      according to the Preferred Reporting Items for Systematic Reviews and Meta
      Analyses (PRISMA) statement protocol. RESULTS: Two trials, DEFINE and CONFIRM
      involved 2 651 patients and compared dimethyl fumarate taken either two or three
      times daily with placebo in patients with RRMS. Additionally in CONFIRM trial
      third group of patients received glatiramer acetate. The overall results of the
      meta-analysis showed that BG-12 (at both dosages) given to patients with RRMS is
      safe and statistically significantly more effective than placebo in reducing the
      proportion of patients who had a relapse by 2 years, the rate of disability
      progression and the mean number of gadolinium-enhancing lesions at 2 years. The
      comparison between BG-12 and glatiramer acetate revealed that the analyzed agent
      could potentially be more effective in the treatment of RRMS. CONCLUSIONS:
      Despite limited RCTs data available, both analyzed BG-12 regimens showed their
      efficacy on clinical disease parameters and other measures of disease activity in
      RRMS. The safety profile of the study agent was acceptable.

PMID- 24851090
TI  - Potential effects of cannabidiol as a wake-promoting agent.
AB  - Over the last decades, the scientific interest in chemistry and pharmacology of
      cannabinoids has increased. Most attention has focused on ?(9)
      tetrahydrocannabinol (?(9)-THC) as it is the psychoactive constituent of Cannabis
      sativa (C. sativa). However, in previous years, the focus of interest in the
      second plant constituent with non-psychotropic properties, cannabidiol (CBD) has
      been enhanced. Recently, several groups have investigated the pharmacological
      properties of CBD with significant findings; furthermore, this compound has
      raised promising pharmacological properties as a wake-inducing drug. In the
      current review, we will provide experimental evidence regarding the potential
      role of CBD as a wake-inducing drug. 

PMID- 24851087
TI  - The glutamatergic aspects of schizophrenia molecular pathophysiology: role of the
      postsynaptic density, and implications for treatment.
AB  - Schizophrenia is one of the most debilitating psychiatric diseases with a
      lifetime prevalence of approximately 1%. Although the specific molecular
      underpinnings of schizophrenia are still unknown, evidence has long linked its
      pathophysiology to postsynaptic abnormalities. The postsynaptic density (PSD) is
      among the molecular structures suggested to be potentially involved in
      schizophrenia. More specifically, the PSD is an electron-dense thickening of
      glutamatergic synapses, including ionotropic and metabotropic glutamate
      receptors, cytoskeletal and scaffolding proteins, and adhesion and signaling
      molecules. Being implicated in the postsynaptic signaling of multiple
      neurotransmitter systems, mostly dopamine and glutamate, the PSD constitutes an
      ideal candidate for studying dopamine-glutamate disturbances in schizophrenia.
      Recent evidence suggests that some PSD proteins, such as PSD-95, Shank, and Homer
      are implicated in severe behavioral disorders, including schizophrenia. These
      findings, further corroborated by genetic and animal studies of schizophrenia,
      offer new insights for the development of pharmacological strategies able to
      overcome the limitations in terms of efficacy and side effects of current
      schizophrenia treatment. Indeed, PSD proteins are now being considered as
      potential molecular targets against this devastating illness. The current paper
      reviews the most recent hypotheses on the molecular mechanisms underlying
      schizophrenia pathophysiology. First, we review glutamatergic dysfunctions in
      schizophrenia and we provide an update on postsynaptic molecules involvement in
      schizophrenia pathophysiology by addressing both human and animal studies.
      Finally, the possibility that PSD proteins may represent potential targets for
      new molecular interventions in psychosis will be discussed. 

PMID- 24851091
TI  - Evidence for an immune role on cognition in schizophrenia: a systematic review.
AB  - OBJECTIVE: Recent evidence has associated immune and inflammatory changes to
      cognitive performance in many diseases, including schizophrenia. Since this is a
      new research field where concepts are not yet solid and new questions and
      hypothesis are still arising, the present study aimed at summarizing the
      available clinical data associating schizophrenia, cognition and
      inflammation/immune function. METHODS: A SYSTEMATIC REVIEW OF THE LITERATURE WAS
      MADE BY SEARCHING THE FOLLOWING TERMS IN MEDLINE: "schizophrenia or psychosis or
      psychotic" AND "inflamm* or immun* or cytokine or IL-* or TNF-* or kynureni* or
      KYNA", AND "cognit* or attention or memory or executive function". RESULTS:
      Seventy five papers were identified using the selected terms, and seven papers
      were included in the review. Papers excluded focused mainly on basic research or
      other neuropsychiatric disorders. CONCLUSIONS: Recent findings link inflammatory
      markers to cognition in schizophrenia, suggesting that inflammation is associated
      with worst cognitive performance. Microglial activation, monoaminergic imbalance,
      brain abnormalities and the kynurenine pathway are possible mechanisms underlying
      cognitive impairment in schizophrenia. Clinical trials with addition of
      immunomodulatory drugs have shown promising results, opening new windows to
      tackle cognition in schizophrenia.

PMID- 24851092
TI  - Effects of the KIBRA Single Nucleotide Polymorphism on Synaptic Plasticity and
      Memory: A Review of the Literature.
AB  - There has been a great deal of interest recently in genetic effects on
      neurocognitive performance in the healthy population. KIBRA -a postsynaptic
      protein from the WWC family of proteins- was identified in 2003 in the human
      brain and kidney and has recently been associated with memory performance and
      synaptic plasticity. Through genome-wide screening, a single nucleotide
      polymorphism (SNP) was detected in the ninth intron of KIBRA gene (T-> C
      substitution) and was implicated in human memory and the underlying neuronal
      circuitry. This review presents a synopsis of the current findings on the effects
      of the KIBRA SNP on human memory and synaptic plasticity. Overall the findings
      suggest impaired memory performance and less efficient or impaired
      hippocampal/medial temporal lobe (MTL) activation in CC homozygotes (in
      comparison to T carriers) with some differences between young and older subjects.
      This review also highlights limitations and potential sources for variability of
      studies' imaging findings along with future perspectives and implications for the
      role of KIBRA in memory-related brain systems. 

PMID- 24851094
TI  - Graphical abstracts.

PMID- 24851093
TI  - Herbal Insomnia Medications that Target GABAergic Systems: A Review of the
      Psychopharmacological Evidence.
AB  - Insomnia is a common sleep disorder which is prevalent in women and the elderly.
      Current insomnia drugs mainly target the gamma-aminobutyric acid (GABA) receptor,
      melatonin receptor, histamine receptor, orexin, and serotonin receptor. GABAA
      receptor modulators are ordinarily used to manage insomnia, but they are known to
      affect sleep maintenance, including residual effects, tolerance, and dependence.
      In an effort to discover new drugs that relieve insomnia symptoms while avoiding
      side effects, numerous studies focusing on the neurotransmitter GABA and herbal
      medicines have been conducted. Traditional herbal medicines, such as Piper
      methysticum and the seed of Zizyphus jujuba Mill var. spinosa, have been widely
      reported to improve sleep and other mental disorders. These herbal medicines have
      been applied for many years in folk medicine, and extracts of these medicines
      have been used to study their pharmacological actions and mechanisms. Although
      effective and relatively safe, natural plant products have some side effects,
      such as hepatotoxicity and skin reactions effects of Piper methysticum. In
      addition, there are insufficient evidences to certify the safety of most
      traditional herbal medicine. In this review, we provide an overview of the
      current state of knowledge regarding a variety of natural plant products that are
      commonly used to treat insomnia to facilitate future studies. 

PMID- 24851095
TI  - HVEM is a TNF Receptor with Multiple Regulatory Roles in the Mucosal Immune
      System.
AB  - The herpes virus entry mediator (HVEM) is a member of the tumor necrosis factor
      receptor superfamily (TNFRSF), and therefore it is also known as TNFRSF14 or
      CD270 (1,2). In recent years, we have focused on understanding HVEM function in
      the mucosa of the intestine, particularly on the role of HVEM in colitis
      pathogenesis, host defense and regulation of the microbiota (2,3,4). HVEM is an
      unusual TNF receptor because of its high expression levels in the gut epithelium,
      its capacity to bind ligands that are not members of the TNF super family,
      including immunoglobulin (Ig) superfamily members BTLA and CD160, and its bi
      directional functionality, acting as a signaling receptor or as a ligand for the
      receptor BTLA. Clinically, Hvem recently was reported as an inflammatory bowel
      disease (IBD) risk gene as a result of genome wide association studies (5,6).
      This suggests HVEM could have a regulatory role influencing the regulation of
      epithelial barrier, host defense and the microbiota. Consistent with this, using
      mouse models, we have revealed how HVEM is involved in colitis pathogenesis,
      mucosal host defense and epithelial immunity (3,7). Although further studies are
      needed, our results provide the fundamental basis for understanding why Hvem is
      an IBD risk gene, and they confirm that HVEM is a mucosal gatekeeper with
      multiple regulatory functions in the mucosa. 

PMID- 24851096
TI  - Advances in systems biology approaches for autoimmune diseases.
AB  - Because autoimmune diseases (AIDs) result from a complex combination of genetic
      and epigenetic factors, as well as an altered immune response to endogenous or
      exogenous antigens, systems biology approaches have been widely applied. The use
      of multi-omics approaches, including blood transcriptomics, genomics,
      epigenetics, proteomics, and metabolomics, not only allow for the discovery of a
      number of biomarkers but also will provide new directions for further
      translational AIDs applications. Systems biology approaches rely on high
      throughput techniques with data analysis platforms that leverage the assessment
      of genes, proteins, metabolites, and network analysis of complex biologic or
      pathways implicated in specific AID conditions. To facilitate the discovery of
      validated and qualified biomarkers, better-coordinated multi-omics approaches and
      standardized translational research, in combination with the skills of
      biologists, clinicians, engineers, and bioinformaticians, are required. 

PMID- 24851097
TI  - Preclinical efficacy and mechanisms of mesenchymal stem cells in animal models of
      autoimmune diseases.
AB  - Mesenchymal stem cells (MSCs) are present in diverse tissues and organs,
      including bone marrow, umbilical cord, adipose tissue, and placenta. MSCs can
      expand easily in vitro and have regenerative stem cell properties and potent
      immunoregulatory activity. They inhibit the functions of dendritic cells, B
      cells, and T cells, but enhance those of regulatory T cells by producing
      immunoregulatory molecules such as transforming growth factor-beta, hepatic
      growth factors, prostaglandin E2, interleukin-10, indolamine 2,3-dioxygenase,
      nitric oxide, heme oxygenase-1, and human leukocyte antigen-G. These properties
      make MSCs promising therapeutic candidates for the treatment of autoimmune
      diseases. Here, we review the preclinical studies of MSCs in animal models for
      systemic lupus erythematosus, rheumatoid arthritis, Crohn's disease, and
      experimental autoimmune encephalomyelitis, and summarize the underlying
      immunoregulatory mechanisms. 

PMID- 24851098
TI  - Kinetics of IFN-gamma and IL-17 Production by CD4 and CD8 T Cells during Acute
      Graft-versus-Host Disease.
AB  - Graft-versus-host disease (GVHD) is a fatal complication that occurs after
      allogeneic hematopoietic stem cell transplantation. To understand the dynamics of
      CD4 and CD8 T cell production of IFN-gamma and IL-17 during GVHD progression, we
      established a GVHD model by transplanting T cell-depleted bone marrow (TCD-BM)
      and purified T cells from B6 mice into irradiated BALB.B, creating an MHC-matched
      but minor histocompatibility (H) antigen-mismatched transplantation (B6 -> BALB.B
      GVHD). Transplantation-induced GVHD was confirmed by the presence of the
      appropriate compositional changes in the T cell compartments and innate immune
      cells in the blood and the systemic secretion of inflammatory cytokines. Using
      this B6 -> BALB.B GVHD model, we showed that the production of IFN-gamma and IL
      17 by CD4 T cells preceded that by CD8 T cells in the spleen, mesenteric lymph
      node, liver, and lung in the BALB.B GVHD host, and Th1 differentiation predated
      Th17 differentiation in all organs during GVHD progression. Such changes in
      cytokine production were based on changes in cytokine gene expression by the T
      cells at different time points during GVHD development. These results demonstrate
      that both IFN-gamma and IL-17 are produced by CD4 and CD8 T cells but with
      different kinetics during GVHD progression. 

PMID- 24851099
TI  - Shigella flexneri Inhibits Intestinal Inflammation by Modulation of Host
      Sphingosine-1-Phosphate in Mice.
AB  - Infection with invasive Shigella species results in intestinal inflammation in
      humans but no symptoms in adult mice. To investigate why adult mice are resistant
      to invasive shigellae, 6~8-week-old mice were infected orally with S. flexneri
      5a. Shigellae successfully colonized the small and large intestines. Mild cell
      death was seen but no inflammation. The infected bacteria were cleared 24 hours
      later. Microarray analysis of infected intestinal tissue showed that several
      genes that are involved with the sphingosine-1-phosphate (S1P) signaling pathway,
      a lipid mediator which mediates immune responses, were altered significantly.
      Shigella infection of a human intestinal cell line modulated host S1P-related
      genes to reduce S1P levels. In addition, co-administration of S1P with shigellae
      could induce inflammatory responses in the gut. Here we propose that Shigella
      species have evasion mechanisms that dampen host inflammatory responses by
      lowering host S1P levels in the gut of adult mice. 

PMID- 24851100
TI  - Phellinus linteus Extract Exerts Anti-asthmatic Effects by Suppressing NF-kappaB
      and p38 MAPK Activity in an OVA-induced Mouse Model of Asthma.
AB  - Phellinus linteus has been used as a traditional herbal medicine in Asian
      countries and is known to have anti-tumor, immunomodulatory, anti-inflammatory,
      and anti-allergic activities. However, the protective effects of P. linteus
      against experimental asthma have not been fully investigated. The objective of
      this study was to determine whether P. linteus ethanol extract (PLE) suppresses
      inflammatory response in an OVA-induced asthma model. As expected, the oral
      administration of PLE significantly inhibited eosinophilic airway inflammation
      and airway hyperresponsiveness in OVA-challenged BALB/c mice. Supporting these
      data, the augmentation of Th2 cytokines (IL-4, IL-5, and IL-13), eotaxin, and
      adhesion molecules in lung tissues and bronchoalveolar lavage fluid after OVA
      inhalation was markedly attenuated by PLE. Furthermore, PLE reduced OVA-induced
      activation of NF-kappaB and p38 MAPK in lung tissues. Therefore, our results
      suggest the potential of P. linteus as a therapeutic agent for asthma. 

PMID- 24851101
TI  - The Nuclear Orphan Receptor NR4A1 is Involved in the Apoptotic Pathway Induced by
      LPS and Simvastatin in RAW 264.7 Macrophages.
AB  - Macrophage death plays a role in several physiological and inflammatory
      pathologies such as sepsis and arthritis. In our previous work, we showed that
      simvastatin triggers cell death in LPS-activated RAW 264.7 mouse macrophage cells
      through both caspase-dependent and independent apoptotic pathways. Here, we show
      that the nuclear orphan receptor NR4A1 is involved in a caspase-independent
      apoptotic process induced by LPS and simvastatin. Simvastatin-induced NR4A1
      expression in RAW 264.7 macrophages and ectopic expression of a dominant-negative
      mutant form of NR4A1 effectively suppressed both DNA fragmentation and the
      disruption of mitochondrial membrane potential (MMP) during LPS- and simvastatin
      induced apoptosis. Furthermore, apoptosis was accompanied by Bcl-2-associated X
      protein (Bax) translocation to the mitochondria. Our findings suggest that NR4A1
      expression and mitochondrial translocation of Bax are related to simvastatin
      induced apoptosis in LPS-activated RAW 264.7 macrophages. 

PMID- 24851102
TI  - Cancer statistics in Korea: incidence, mortality, survival, and prevalence in
      2011.
AB  - PURPOSE: This study aimed to report nationwide cancer statistics in Korea,
      including incidence, mortality, survival, and prevalence, and their trends.
      MATERIALS AND METHODS: Incidence data from 1993 to 2011 were obtained from the
      Korea National Cancer Incidence Database, and vital status was followed through
      December 31, 2012. Mortality data from 1983 to 2011 were obtained from Statistics
      Korea. Crude and age-standardized rates for incidence, mortality, and prevalence,
      and relative survival were calculated. RESULTS: A total of 218,017 cancer cases
      and 71,579 cancer deaths were reported to have occurred in 2011, and there were
      1,097,253 prevalent cases identified in Korea as of January 1, 2012. Over the
      past 13 years (1999-2011), overall incidence rates have increased by 3.4% per
      year. The incidence rates of liver and cervical cancers have decreased, while
      those of thyroid, breast, prostate, and colorectal cancers have increased.
      Notably, thyroid cancer increased by 23.3% per year in both sexes, and became the
      most common cancer since 2009. The mortality for all cancers combined decreased
      by 2.7% per year from 2002 to 2011. Five-year relative survival rates of patients
      diagnosed in the last 5 years (2007-2011) have improved by 25.1% compared with
      those from 1993 to 1995. CONCLUSION: Overall cancer mortality rates have declined
      since 2002 in Korea, while incidence has increased rapidly and survival has
      improved.

PMID- 24851103
TI  - Prediction of cancer incidence and mortality in Korea, 2014.
AB  - PURPOSE: We studied and reported on cancer incidence and mortality rates as
      projected for the year 2014 in order to estimate Korea's current cancer burden.
      MATERIALS AND METHODS: Cancer incidence data from 1999 to 2011 were obtained from
      the Korea National Cancer Incidence Database, and cancer mortality data from 1993
      to 2012 were acquired from Statistics Korea. Cancer incidence in 2014 was
      projected by fitting a linear regression model to observed age-specific cancer
      incidence rates against observed years, then multiplying the projected age
      specific rates by the age-specific population. For cancer mortality, a similar
      procedure was employed, except that a Joinpoint regression model was used to
      determine at which year the linear trend changed significantly. RESULTS: A total
      of 265,813 new cancer cases and 74,981 cancer deaths are expected to occur in
      Korea in 2014. Further, the crude incidence rate per 100,000 of all sites
      combined will likely reach 524.7 and the age-standardized incidence rate, 338.5.
      Meanwhile, the crude mortality rate of all sites combined and age-standardized
      rate are projected to be 148.0 and 84.6, respectively. Given the rapid rise in
      prostate cancer cases, it is anticipated to be the fourth most frequently
      occurring cancer site in men for the first time. CONCLUSION: Cancer has become
      the most prominent public health concern in Korea, and as the population ages,
      the nation's cancer burden will continue to increase.

PMID- 24851104
TI  - A nationwide survey of knowledge of and compliance with cancer pain management
      guidelines by korean physicians.
AB  - PURPOSE: Although cancer pain is prevalent, under-treatment still remains a
      problem. Knowledge of and compliance with guidelines for management of cancer
      pain were analyzed for exploration of physician-related barriers to cancer pain
      management. In addition, physicians' knowledge and its correlation with cancer
      pain control were audited. MATERIALS AND METHODS: From July 8 to December 2,
      2010, a nationwide survey of house staff enquired about their knowledge of cancer
      pain control guidelines, and the medical records of patients under their care
      were analyzed. RESULTS: In total, 180 physicians participated in the study. Their
      average score for knowledge was 14.6 (range, 7 to 19; maximum possible, 20). When
      the knowledge score was divided into low, medium, and high scores, patients
      receiving care from physicians with high levels of knowledge tended to have
      better cancer pain control (p<0.001). Of the total patients with severe pain,
      19.5% were not prescribed strong opioids, and 40% were not prescribed any
      medication for breakthrough pain. CONCLUSION: Physicians' knowledge of guidelines
      for control of cancer pain showed an association with improvement of pain
      management. Overall adherence to the guidelines was lacking. Continuous
      interventions such as education and audits regarding cancer pain control
      guidelines for physician are needed.

PMID- 24851105
TI  - Clinical features and treatment of collecting duct carcinoma of the kidney from
      the korean cancer study group genitourinary and gynecology cancer committee.
AB  - PURPOSE: Collecting duct carcinoma (CDC) of the kidney is an aggressive disease
      with a poor prognosis, accountings for less than 1% of all renal cancers. To
      date, no standard therapy for CDC has been established. The aim of this study is
      an investigation of clinicopathologic findings of CDC and correlation of the
      disease status with a prognosis. MATERIALS AND METHODS: From 1996 to 2009, 35
      patients with CDC were treated at eight medical centers. The diagnosis of CDC was
      made based on nephrectomy in 27 cases and renal biopsy in eight cases. RESULTS:
      Median PFS and OS for all patients were 5.8 months (95% CI 3.5 to 9.2) and 54.4
      months (95% CI 0 to 109.2), respectively. The OS of patients with Stages I-III
      was 69.9 months (95% CI 54.0 to 85.8), while that of patients with Stage IV was
      8.6 months (95% CI 0 to 23.3), which showed a statistically significant
      difference (p=0.01). In addition, among patients with Stage IV, the OS of
      patients who received a palliative treatment (immunotherapy, chemotherapy, or
      targeted therapy) was 18.4 months, which was higher than the OS of patients
      without treatment of 4.5 months. CONCLUSION: CDC is a highly aggressive form of
      renal cell carcinoma. Despite most of the treatments, PFS and OS were short,
      however, there were some long-term survivors, therefore, conduct of additional
      research on the predictive markers of the several clinical, pathological
      differences and their treatments will be necessary.

PMID- 24851106
TI  - Impact on Loco-regional Control of Radiochemotherapeutic Sequence and Time to
      Initiation of Adjuvant Treatment in Stage II/III Rectal Cancer Patients Treated
      with Postoperative Concurrent Radiochemotherapy.
AB  - PURPOSE: This study was designed to evaluate the impact of radiochemotherapeutic
      sequence and time to initiation of adjuvant treatment on loco-regional control
      for resected stage II and III rectal cancer. MATERIALS AND METHODS: Treatment
      outcomes for rectal cancer patients from two hospitals with different sequencing
      strategies regarding adjuvant concurrent radiochemotherapy (CRCT) were compared
      retrospectively. Pelvic radiotherapy was administered concurrently on the first
      (early CRCT, n=180) or the third cycle of chemotherapy (late CRCT, n=180). During
      radiotherapy, two cycles of fluorouracil were provided to patients in both
      groups. In the early CRCT group, median six cycles of fluorouracil and leucovorin
      were prescribed during the post-CRCT period. In the late CRCT group, two cycles
      of fluorouracil were administered in the pre- and post-CRCT periods. RESULTS: No
      significant differences in the 5-year loco-regional recurrence-free survival
      (LRRFS) (92.5% vs. 95.6%, p=0.43) or overall survival and disease-free survival
      were observed between groups. Patients who began receiving adjuvant treatment
      later than five weeks after surgery had lower LRRFS than patients who received
      adjuvant treatment within five weeks following surgery (79% vs. 91%, p<0.01). The
      risk of loco-regional recurrence increased as the time to initiation of adjuvant
      treatment was delayed. CONCLUSION: In the current study, treatment outcomes were
      not significantly influenced by the sequence of adjuvant treatment but by the
      delay of adjuvant treatment for more than five weeks. Timely administration of
      adjuvant treatment is deemed important in achieving loco-regional tumor control
      for stage II/III rectal cancer patients.

PMID- 24851107
TI  - Clinical outcomes of local excision following preoperative chemoradiotherapy for
      locally advanced rectal cancer.
AB  - PURPOSE: To evaluate the treatment outcomes of local excision following
      preoperative chemoradiotherapy in patients with locally advanced rectal cancer
      who have not undergone radical surgery for any reason. MATERIALS AND METHODS: The
      data of 27 patients with locally advanced rectal cancer who underwent
      preoperative chemoradiotherapy followed by local excision were analyzed
      retrospectively. The primary endpoint was the 5-year relapse-free survival rate,
      and the secondary endpoint was the pattern of recurrence. RESULTS: The median
      follow-up time was 81.8 months (range, 28.6 to 138.5 months). The 5-year local
      relapse-free survival (LRFS), distant metastasis-free survival (DMFS), relapse
      free survival (RFS), and overall survival (OS) were 88.9%, 81.1%, 77.8%, and
      85.0%, respectively. Six (22%) patients developed treatment failure; one (4%)
      patient had local recurrence only, three (11%) patients had distant recurrence
      only, and two (7%) patients had both. The 5-year LRFS, DMFS, RFS, and OS for
      patients with ypT0-1 compared with ypT2-3 were 94.1% vs. 77.8% (p=0.244), 94.1%
      vs. 55.6% (p=0.016), 88.2% vs. 55.6% (p=0.051), and 94.1% vs. 66.7% (p=0.073),
      respectively. CONCLUSION: Local excision following preoperative chemoradiotherapy
      may be an alternative treatment for highly selected patients with locally
      advanced rectal cancer who have achieved ypT0-1 after preoperative
      chemoradiotherapy.

PMID- 24851108
TI  - Metabolic burden measured by (18)f-fluorodeoxyglucose positron emission
      tomography/computed tomography is a prognostic factor in patients with small cell
      lung cancer.
AB  - PURPOSE: Evidence regarding the usefulness of (18)F-fluorodeoxyglucose positron
      emission tomography/computed tomography ((18)F-FDG PET/CT) in predicting the
      prognosis of non-small cell lung cancer is increasing. However, data on small
      cell lung cancer (SCLC) are scarce. The aim of this study was to evaluate the
      prognostic value of metabolic parameters measured using (18)F-FDG PET/CT in
      patients with SCLC. MATERIALS AND METHODS: We conducted a retrospective review of
      114 patients with pathologically proven SCLC (26 cases of limited disease and 88
      cases of extensive disease) who underwent pretreatment (18)F-FDG PET/CT. The
      maximal SUV (SUVmax) was used quantitatively for determination of FDG PET
      activity. The SUVmax of the primary tumor (primary SUVmax), the sum of SUVmax
      values of malignant lesions (SUVsum), and the mean SUVmax of malignant lesions
      were calculated. RESULTS: The patient population was subdivided using a median
      SUVsum value of 24.6. High SUVsum showed a significant association with known
      factors for poor prognosis, including higher neuron-specific enolase (p=0.010),
      CYFRA 21-1 (p=0.014), and extensive disease status (p=0.007). Patients with high
      SUVsum had significantly shorter median overall survival (6.6 months vs. 13.0
      months, p<0.001) and progression-free survival (5.2 months vs. 8.0 months,
      p<0.001) than patients with low SUVsum. Results of multivariate analysis showed
      that SUVsum, chemotherapy cycles, and the response to first-line treatment were
      significant prognostic factors of survival. In contrast, mean SUVmax and primary
      SUVmax were not significant predictors of survival. CONCLUSION: In this study,
      metabolic burden represented by SUVsum from pretreatment (18)F-FDG PET/CT was an
      independent prognostic factor in patients with SCLC.

PMID- 24851109
TI  - Modified MVAC as a Second-Line Treatment for Patients with Metastatic Urothelial
      Carcinoma after Failure of Gemcitabine and Cisplatin Treatment.
AB  - PURPOSE: There is no established standard second-line chemotherapy for patients
      with advanced or metastatic urothelial carcinoma (UC) who failed gemcitabine and
      cisplatin (GC) chemotherapy. This study was conducted in order to investigate the
      efficacy and toxicity of modified methotrexate, vinblastine, doxorubicin, and
      cisplatin (MVAC) in patients with metastatic UC previously treated with GC.
      MATERIALS AND METHODS: We retrospectively analyzed 28 patients who received
      modified MVAC between November 2004 and November 2012. All patients failed prior,
      first-line GC chemotherapy. RESULTS: The median age of patients was 64.0 years
      (range, 33.0 to 77.0 years), and 23 (82.1%) patients had an Eastern Cooperative
      Oncology Group performance status of 0 or 1. The overall response rate and the
      disease control rate were 36.0% and 64.0%, respectively. After a median follow-up
      period of 38 weeks (range, 5 to 182 weeks), median progression free survival was
      21.0 weeks (95% confidence interval [CI], 6.3 to 35.7 weeks) and median overall
      survival was 49.0 weeks (95% CI, 18.8 to 79.3 weeks). Grade 3 or 4 hematological
      toxicities included neutropenia (n=21, 75.0%) and anemia (n=9, 32.1%). Grade 3 or
      4 non-hematological toxicities did not occur and there was no treatment-related
      death. CONCLUSION: Modified MVAC appears to be a safe and active chemotherapy
      regimen in patients with stable physical status and adequate renal function after
      GC treatment.

PMID- 24851110
TI  - Diagnostic Value of Circulating Extracellular miR-134, miR-185, and miR-22 Levels
      in Lung Adenocarcinoma-Associated Malignant Pleural Effusion.
AB  - PURPOSE: The accurate and timely diagnosis of malignant pleural effusion (MPE) in
      lung cancer patients is important because MPE has a poor prognosis and is
      classified as stage IV disease. Molecular biomarkers for pleural effusion, such
      as circulating extracellular microRNAs (miRNAs) isolated from pleural fluid, may
      help in the diagnosis of MPE. The present study examined whether miRNAs that are
      deregulated in lung cancer (miR-134, miR-185, and miR-22) can serve as diagnostic
      markers for lung adenocarcinoma-associated MPE (LA-MPE). MATERIALS AND METHODS:
      Real-time reverse transcription quantitative polymerase chain reaction was used
      to measure the expression of the three miRNAs in samples from 87 patients with
      pleural effusion comprising 45 LA-MPEs and 42 benign pleural effusions (BPEs).
      The area under the receiver operating characteristic curve (AUC) was then used to
      evaluate the diagnostic performance of each of the three miRNAs and compare it
      with that of the common tumor marker, carcinoembryonic antigen (CEA). RESULTS:
      The expression of all three miRNAs was significantly lower in LA-MPE than in BPE
      (p <0.001). The AUCs for miR-134, miR-185, miR-22, and CEA were 0.721, 0.882,
      0.832, and 0.898, respectively. Combining CEA with the three miRNAs increased the
      diagnostic performance, yielding an AUC of 0.942 (95% confidence interval, 0.864
      to 0.982), with a sensitivity of 91.9% and a specificity of 92.5%. CONCLUSION:
      The present study suggests that the expression levels of circulating
      extracellular miR-134, miR-185, and miR-22 in patients with pleural effusion may
      have diagnostic value when differentiating between LA-MPE and BPE.

PMID- 24851111
TI  - Preclinical efficacy testing for stomach and liver cancers.
AB  - PURPOSE: Hollow fiber assays offer an early in vivo method of anticancer drug
      screening. The assays have been optimized for human cancers originating from the
      lung, breast, colon, ovary, and brain, but not from the stomach and liver. The
      current study focused on optimization of hollow fiber assays for gastric and
      hepatocellular carcinoma cell lines. MATERIALS AND METHODS: Gastric (SNU-16, SNU
      484, SNU-668) and hepatocellular (HepG2, SK-Hep-1, Hep3B) carcinoma cell lines in
      hollow fibers were transplanted subcutaneously and intraperitoneally into mice,
      which were subsequently treated with a standard anticancer agent, paclitaxel. The
      hollow fiber activity of paclitaxel in each cell line was compared with the
      xenograft activity. RESULTS: Using optimized inoculation densities and schedules,
      treatment with paclitaxel was effective in gastric carcinoma cell lines, SNU-16
      and SNU-484, but not in SNU-668. In the hollow fiber assays, paclitaxel was
      effective in hepatocellular carcinoma cell lines, HepG2 and SK-Hep-1, but not in
      Hep3B. Consistent with the results of the hollow fiber assay, SNU-16 and SNU-484,
      but not SNU-668, showed tumor regression, and HepG2 and SK-Hep-1, but not Hep3B,
      showed effective tumor responses following treatment with paclitaxel in xenograft
      models. When EW7197, a novel compound, and flavopiridol were tested in SNU-16
      cells under optimized conditions, the hollow fiber activity showed good
      correlation with the xenograft activity of each compound. CONCLUSION: Our
      protocols may be useful for screening candidate small molecules that may exhibit
      activity against stomach and liver cancers, both of which are common in Korea.

PMID- 24851112
TI  - Case series of different onset of skin metastasis according to the breast cancer
      subtypes.
AB  - We report on five cases of skin metastasis according to the breast cancer (BC)
      subtype. Two cases of HER2 positive BC showed only skin metastasis after
      immediate postoperative period and rapid clinical response to targeted therapy.
      Another two cases of triple negative BC showed thyroid and lung metastasis in
      addition to skin metastasis, and their response of cytotoxic chemotherapy was not
      definite. The other hormone positive BC showed skin metastasis only, with a
      longer, slower, less progressive pattern than other subtypes. Most cases of skin
      metastasis were detected at terminal stage of malignancy and were considered to
      have a limited survival period. However, some BC patients can survive longer if
      the targeted agents are effective. Therefore, physicians should provide detailed
      follow up of BC after curative treatment and understand the metastatic pattern of
      BC according to the subtype. 

PMID- 24851113
TI  - Intra-tumoral Metastatic Double Primary Carcinoma: Synchronous Metastatic Tumor
      in Lung from Breast and Thyroid Carcinoma.
AB  - Cases of phenotypic heterogeneity of cells within tumors have recently been
      reported. Here, we report on a patient with characteristic intra-tumor double
      primary metastases in the lung. This patient was a 40-year-old Korean woman who
      had been diagnosed with breast cancer (T1N0M0, estrogen receptor/progesterone
      receptor/HER2 +/+/+) and papillary thyroid cancer three years prior and underwent
      a complete surgical resection followed by appropriate adjuvant treatment with
      radiation, hormone, and radioactive iodine. She was recently admitted for newly
      developed pulmonary nodules. Metastasectomy through video-assisted thoracoscopic
      surgery revealed recurrent double primary cancer with two different components
      (metastatic ductal carcinomas from the breast and metastatic papillary carcinomas
      from the thyroid gland) in each pulmonary nodule in the right upper lobe and
      right middle lobe. To the best of our knowledge, this is the first report of
      simultaneous recurrent double metastasis in one organ from different primary
      origins. 

PMID- 24851114
TI  - Tumor lysis syndrome in a patient with metastatic colon cancer after treatment
      with 5-fluorouracil/leucovorin and oxaliplatin: case report and literature
      review.
AB  - Development of tumor lysis syndrome (TLS) may occur after chemotherapy or
      spontaneously in bulky or rapidly growing tumors. This syndrome is frequent but
      preventable in patients with hematologic malignancies. TLS following therapy has
      been reported infrequently in various types of solid tumors. TLS associated with
      oxaliplatin containing chemotherapy in a solid tumor has never been reported. A
      59-year-old man received 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX)
      chemotherapy for metastatic colon cancer. Development of TLS occurred three days
      after administration of chemotherapy. Two days later, his abnormal laboratory
      findings were recovered with appropriate management. To the best of our
      knowledge, the current case is the first report on development of acute TLS
      following oxaliplatin containing chemotherapy in a patient with colon cancer. We
      also review the literature on tumor lysis syndrome in patients with colorectal
      cancer. 

PMID- 24851115
TI  - Strategies for Early Non-response to Antipsychotic Drugs in the Treatment of
      Acute-phase Schizophrenia.
AB  - As a strategy for antipsychotic treatment of schizophrenia, monotherapy is
      clearly optimal when both effective and tolerated. When a patient fails to
      respond to an adequate dose of an antipsychotic, alternatives include switching,
      administering a higher dose (above the licensed dose), polypharmacy or clozapine.
      Clozapine is the only option with established efficacy, but is less manageable
      than other antipsychotics. We therefore reviewed other options, focusing on the
      treatment of acute-phase schizophrenia. According to recent evidence, an
      antipsychotic may be viewed as ineffective within 1-4 weeks in acute-phase
      practice, although some differences may exist among antipsychotics. Whether a
      switching strategy is effective might depend on the initial antipsychotic and
      which antipsychotic is switched to. As weak evidence points toward augmentation
      being superior to continuation of the initial antipsychotic, inclusion of
      augmentation arms in larger studies comparing strategies for early non-responders
      in the acute-phase is justified. With respect to high-doses, little evidence is
      available regarding acute-phase treatment, and the issue remains controversial.
      Although evidence for antipsychotic switching, augmentation, and high-doses has
      gradually been accumulating, more studies performed in real clinical practice
      with minimal bias are required to establish strategies for early non-response to
      an antipsychotic drug in the treatment of acute-phase schizophrenia. 

PMID- 24851116
TI  - Neuroimmunological aberrations and cerebral asymmetry abnormalities in
      schizophrenia: select perspectives on pathogenesis.
AB  - Within the wide-ranging gamut of factors that comprise gene-environment
      interactions postulated to underlie schizophrenia, the crosstalk between
      environmental factors and feto-maternal immune components has been put forth as
      one of the important mechanisms that increase the risk towards schizophrenia in
      the offspring. Interestingly, immune factors have been shown to critically
      modulate the brain development during the prenatal stages. Moreover the past many
      decades, influential theoretical propositions and evidence base (albeit not
      unequivocally) have compellingly linked prenatal sex hormonal status to
      critically provoke long lasting immunological changes and subsequently affect
      developmental programming of cerebral asymmetry in schizophrenia. In this review,
      we summarize the select perspectives emphasizing the role of neuroimmunoendocrine
      pathways in anomalous cerebral asymmetry in contemporary understanding of
      schizophrenia pathogenesis. 

PMID- 24851118
TI  - Effects of Brilliant Blue G on Serum Tumor Necrosis Factor-alpha Levels and
      Depression-like Behavior in Mice after Lipopolysaccharide Administration.
AB  - OBJECTIVE: Accumulating evidence suggests that inflammation plays a role in the
      pathophysiology of major depression. The adenosine triphosphate (ATP)-sensitive
      P2X7 receptor (P2X7R) plays a crucial role in microglial activation caused by
      inflammation. The dye brilliant blue G (BBG) is a P2X7R antagonist. This study
      examined whether BBG shows antidepressant effects in an inflammation-induced
      model of depression. METHODS: We examined the effects of BBG (12.5, 25, or 50
      mg/kg) on serum tumor necrosis factor-alpha (TNF-alpha) levels after
      administering the bacterial endotoxin lipopolysaccharide (LPS; 0.5 mg/kg) and the
      effects of BBG (50 mg/kg) on depression-like behavior in the tail-suspension test
      (TST) and forced swimming test (FST). RESULTS: Pretreatment with BBG (12.5, 25,
      or 50 mg/kg) significantly blocked the increase in serum TNF-alpha levels after a
      single dose of LPS (0.5 mg/kg). Furthermore, BBG (50 mg/kg) significantly
      attenuated the increase in immobility time in the TST and FST after LPS (0.5
      mg/kg) administration. CONCLUSION: The results suggest that BBG has anti
      inflammatory and antidepressant effects in mice after LPS administration.
      Therefore, P2X7R antagonists are potential therapeutic drugs for inflammation
      related major depression.

PMID- 24851117
TI  - Advanced pharmacotherapy evidenced by pathogenesis of autism spectrum disorder.
AB  - In clinical practice, pharmacological treatment is mostly focused on behavioral
      symptoms in everyday life. Nevertheless, persistent effort continues to develop
      medication for causal treatment. Recent changes in diagnostic criteria from
      Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision
      (DSM-IV-TR) to DSM-5 would affect not only diagnosing approaches, but also
      therapeutic approaches. Because previous pervasive developmental disorders have
      been integrated into a single entity, the autism spectrum disorder (ASD), we have
      to prepare for what medications are valuable for the ASD. In this article, we
      reviewed the following etiological treatment: acetylcholine and glutamate related
      medicine; amino acid medicine such as secretin, endogenous opioid, and oxytocin;
      complementary and alternative medicine such as chelating agents, vitamins, and
      omega-3; promising drugs related to the scope of pharmacogenetics currently under
      study. 

PMID- 24851119
TI  - Duloxetine, a Selective Noradrenaline Reuptake Inhibitor, Increased Plasma Levels
      of 3-Methoxy-4-hydroxyphenylglycol but Not Homovanillic Acid in Patients with
      Major Depressive Disorder.
AB  - OBJECTIVE: We investigated the effects of duloxetine on the plasma levels of
      catecholamine metabolites and serum brain-derived neurotrophic factor (BDNF) in
      64 patients with major depressive disorder (MDD). METHODS: Major depressive
      episode was diagnosed using the Structured Clinical Interview for the Diagnostic
      and Statistical Manual of Mental Disorders-fourth edition (DSM-IV) according to
      the DSM-IV text revision (DSM-IV-TR) criteria. The severity of depression was
      evaluated using the 17-item Hamilton Rating Scale for Depression (HAMD-17). Blood
      sampling and clinical evaluation were performed on days 0, 28, and 56. RESULTS:
      Duloxetine treatment for 8 weeks significantly increased the plasma 3-methoxy-4
      hydroxyphenylglycol (MHPG) levels but not the homovanillic acid (HVA) levels in
      responders with MDD. CONCLUSION: These results imply that noradrenaline plays an
      important role in alleviating depressive symptoms.

PMID- 24851120
TI  - Comparison of Memory Function and MMPI-2 Profile between Post-traumatic Stress
      Disorder and Adjustment Disorder after a Traffic Accident.
AB  - OBJECTIVE: Differential diagnosis between post-traumatic stress disorder (PTSD)
      and adjustment disorder (AD) is rather difficult, but very important to the
      assignment of appropriate treatment and prognosis. This study investigated
      methods to differentiate PTSD and AD. METHODS: Twenty-five people with PTSD and
      24 people with AD were recruited. Memory tests, the Minnesota Multiphasic
      Personality Inventory 2 (MMPI-2), and Beck's Depression Inventory were
      administered. RESULTS: There were significant decreases in immediate verbal
      recall and delayed verbal recognition in the participants with PTSD. The reduced
      memory functions of participants with PTSD were significantly influenced by
      depressive symptoms. Hypochondriasis, hysteria, psychopathic deviate, paranoia,
      schizophrenia, post-traumatic stress disorder scale of MMPI-2 classified
      significantly PTSD and AD group. CONCLUSION: Our results suggest that verbal
      memory assessments and the MMPI-2 could be useful for discriminating between PTSD
      and AD.

PMID- 24851121
TI  - Drug Treated Schizophrenia, Schizoaffective and Bipolar Disorder Patients
      Evaluated by qEEG Absolute Spectral Power and Mean Frequency Analysis.
AB  - OBJECTIVE: Research of electroencephalograph (EEG) power spectrum and mean
      frequency has shown inconsistent results in patients with schizophrenic,
      schizoaffective and bipolar disorders during medication when compared to normal
      subjects thus; the characterization of these parameters is an important task.
      METHODS: We applied quantitative EEG (qEEG) to investigate 38 control, 15
      schizophrenic, 7 schizoaffective and 11 bipolar disorder subjects which remaine
      under the administration of psychotropic drugs (except control group). Absolute
      spectral power (ASP), mean frequency and hemispheric electrical asymmetry were
      measured by 19 derivation qEEG. Group mean values were compared with non
      parametrical Mann-Whitney test and spectral EEG maps with z-score method at p <
      0.05. RESULTS: Most frequent drug treatments for schizophrenic patients were
      neuroleptic+antiepileptic (40% of cases) or 2 neuroleptics (33.3%).
      Schizoaffective patients received neuroleptic+benzodiazepine (71.4%) and for
      bipolar disorder patients neuroleptic+antiepileptic (81.8%). Schizophrenic (at
      all derivations except for Fp1, Fp2, F8 and T6) and schizoaffective (only at C3)
      show higher values of ASP (+57.7% and +86.1% respectively) compared to control
      group. ASP of bipolar disorder patients did not show differences against control
      group. The mean frequency was higher at Fp1 (+14.2%) and Fp2 (+17.4%) in bipolar
      disorder patients than control group, but no differences were found in
      frequencies between schizophrenic or schizoaffective patients against the control
      group. Majority of spectral differences were found at the left hemisphere in
      schizophrenic and schizoaffective but not in bipolar disorder subjects.
      CONCLUSION: The present report contributes to characterize quantitatively the
      qEEG in drug treated schizophrenic, schizoaffective or bipolar disorder patients.

PMID- 24851123
TI  - Successful Treatment of Anorexia Nervosa in a 10-year-old Boy with Risperidone
      Long-acting Injection.
AB  - Although the effectiveness of medication in the treatment of anorexia nervosa is
      uncertain, atypical antipsychotics such as olanzapine and risperidone have been
      used empirically for decades. we describe the case of a 10-year-old boy with
      anorexia nervosa in whom remarkable improvement was seen following the
      administration of risperidone or risperidone long-acting injection and
      deterioration when these agents were ceased. Because this is, to the best of our
      knowledge, the first report describing the usefulness of risperidone long-acting
      injection for adolescent anorexia nervosa. 

PMID- 24851124
TI  - A case of acute pancreatitis associated with risperidone treatment.
AB  - Acute pancreatitis with antipsychotic treatment is rare but sometimes causes a
      fatal adverse effect. Most cases of acute pancreatitis due to atypical
      antipsychotic agents are reported to occur within six months of starting
      antipsychotic administration. Acute pancreatitis caused by risperidone is rare.
      The patient had a high fever, stomachache and vomiting. The results of the
      abdominal computed tomograhpy scan were negative. The results of the abdominal
      ultrasonography were positive for gallstones in gallbladder and distention of the
      common bile duct. She had been fasting and received antibiotic intravenous
      injections. Amylase and lipase titers were high. After risperidone
      discontinuation, both the levels of the amylase and the lipase were gradually
      decreased. Three months later, the patient still maintains a good clinical
      balance. Although atypical antipsychotic-induced pancreatitis has been reported
      in conjunction with hyperglycemia, the pathophysiologic mechanism of these
      adverse events remains unclear. This case got pancreatitis 6 month after
      risperidone treatment. Using the antipsychotic agents, it is necessary to monitor
      pancreas function. 

PMID- 24851122
TI  - A Pilot Study for Discovering Candidate Genes of Chromosome 18q21 in
      Methamphetamine Abusers: Case-control Association Study.
AB  - OBJECTIVE: It was previously suggested that the malic enzyme 2 (ME2) as the
      candidate gene for psychosis in fine mapping of chromosome 18q21. Chromosome
      18q21 is also one of the possible regions that can contribute to addiction.
      METHODS: We performed a pilot study for discovering candidate gene of chromosome
      18q21 in the methamphetamine abusers for elucidating the candidate gene for
      methamphetamine addiction leading to psychosis. We have selected 30 unrelated
      controls (16 males, 14 females; age=59.8+/-10.4) and 37 male methamphetamine
      abusers (age=43.3+/-7.8). We analyzed 20 single nucleotide polymorphisms (SNPs)
      of 7 neuronal genes in chromosome 18q21 for DNA samples that was checked for the
      data quality and genotype error. The association between the case-control status
      and each individual SNP was measured using multiple logistic regression models
      (adjusting for age and sex as covariates). And we controlled false discovery rate
      (FDR) to deal with multiple testing problem. RESULTS: We found 3 significant SNPs
      of 2 genes in chromosome 18q21 (p-value<0.05; adjusting for age as covariate) in
      methamphetamine abusers compared to controls. We also found 2 significant SNPs of
      1 gene (p-value<0.05; adjusting for age and sex as covariates) (rs3794899,
      rs3794901:MAPK4). Two SNPs in MAPK4 gene were significant in both statistical
      groups. CONCLUSION: MAPK4, the gene for mitogen-activated protein kinase 4, is
      one of the final 6 candidate genes including ME2 in 18q12-21 in our previous
      finemapping for psychosis. Our results suggest that MAPK4 can be a candidate gene
      that contribute to the methamphetamine addiction leading to psychosis.

PMID- 24851125
TI  - A case of aripiprazole induced tardive dyskinesia in a neuroleptic-naive patient
      with two years of follow up.
AB  - Tardive dyskinesia (TD) is arguably the most serious and potential irreversible
      side effect of antipsychotic medication. Traditionally first generation
      antipsychotics are the neuroleptics considered to have higher risk of TD as
      compared to second and third generation antipsychotics. Aripiprazole is a third
      generation antipsychotic with a novel mechanism of action. Risk of developing TD
      with use of aripiprazole has been unknown. Recently many cases of aripiprazole
      associated TD have been reported. A case of 52 year old Caucasian woman is
      discussed who presented to us with first manic episode. Patient had never been
      treated with any antipsychotic medication in her life before. During current
      episode, she was treated with aripiprazole 30 mg/day. During follow up, patient
      was found to have developed dyskinetic oro-facial movements within 2 months of
      starting aripiprazole. She was not taking any other antipsychotic/anti
      dopaminergic medication at that time. Patient's abnormal oro-facial movements
      could not be reversed in spite of immediate discontinuation of aripiprazole.
      Multiple medications are tried over the next 2 years but her movement disorder
      never remitted. Above case (along with other recent reports) suggest that risk of
      movement disorder with aripiprazole use could be higher than previously thought.
      Further studies are required to find out incidence of movement disorder with
      aripiprazole. Aripiprazole use should be preferably restricted to FDA approved
      indications. Clinician needs to be very vigilant about emergence of any movement
      disorder while using aripiprazole, especially in patients with risk factors for
      TD. 

PMID- 24851126
TI  - The R-Stereoisomer of Ketamine as an Alternative for Ketamine for Treatment
      resistant Major Depression.

PMID- 24851127
TI  - Tuberculous pleurisy: an update.
AB  - Tuberculous pleurisy is the most common form of extrapulmonary tuberculosis in
      Korea. Tuberculous pleurisy presents a diagnostic and therapeutic problem due to
      the limitations of traditional diagnostic tools. There have been many clinical
      research works during the past decade. Recent studies have provided new insight
      into the tuberculous pleurisy, which have a large impact on clinical practice.
      This review is a general overview of tuberculous pleurisy with a focus on recent
      findings on the diagnosis and management. 

PMID- 24851128
TI  - Pleural infection and empyema.
AB  - Increasing incidence of pleural infection has been reported worldwide in recent
      decades. The pathogens responsible for pleural infection are changing and differ
      from those in community acquired pneumonia. The main treatments for pleural
      infection are antibiotics and drainage of infected pleural fluid. The efficacy of
      intrapleural fibrinolytics remains unclear, although a recent randomized control
      study showed that the novel combination of tissue plasminogen activator and
      deoxyribonuclease had improved clinical outcomes. Surgical drainage is a critical
      treatment in patient with progression of sepsis and failure in tube drainage. 

PMID- 24851129
TI  - Usefulness of sputum induction with hypertonic saline in a real clinical practice
      for bacteriological yields of active pulmonary tuberculosis.
AB  - BACKGROUND: Mycobacterial identification in active pulmonary tuberculosis (APTB)
      is confirmative, even though successful rates using self-expectorated sputum are
      limited. Sputum specimens collected by hypertonic saline nebulization showed
      higher bacteriologic diagnostic sensitivities over those of self-expectoration,
      mostly studied in smear-negative or sputum-scarce patients. The efficacy of
      induced sputum was rarely assessed in real clinical settings. METHODS: A
      prospective randomized case-control study was performed in one hospital. The
      subjects highly suspicious of APTB were asked to provide 3 pairs of sputum
      specimens in 3 consecutive days. The first pairs of the specimens were obtained
      either by self-expectoration (ES) from the next day of the visit or sputum
      induction with 7% saline nebulization in clinic (SI), and the other specimens
      were collected in the same way. The samples were tested in microscopy, culture,
      and polymerase chain reaction (PCR). The outcomes of the bacteriological
      diagnosis were compared. RESULTS: Seventy six patients were assigned to either ES
      (38 subjects, median age of 51, 65.8% male) or SI (38 subjects, median age of 55,
      52.6% male). APTB was clinically confirmed in 51 patients (70.8%), 27 in ES and
      24 in SI. Among the APTB, more adequate specimens were collected from SI (41/65,
      63.1%) than ES (34/80, 42.5%) (p=0.01). Bacteriological confirmation was achieved
      in 14 (58.3%) patients in SI, and 13 (48.1%) in ES (p=0.46). In the same-day
      bacteriological diagnosis with microscopy and PCR, there were positive results
      for 9 patients (37.5%) in SI and 7 patients (25.9%) in ES (p=0.37). CONCLUSION:
      Sputum induction improves sputum specimen adequacy. It may be useful for the same
      day bacteriological diagnosis with microscopic examination and PCR.

PMID- 24851130
TI  - Study Design and Outcomes of Korean Obstructive Lung Disease (KOLD) Cohort Study.
AB  - BACKGROUND: The Korean Obstructive Lung Disease (KOLD) Cohort Study is a
      prospective longitudinal study of patients with chronic obstructive pulmonary
      disease (COPD), asthma, or other unclassified obstructive lung diseases. It was
      designed to develop new classification models and biomarkers that predict
      clinically relevant outcomes for patients with obstructive lung diseases.
      METHODS: Patients over 18 years old who have chronic respiratory symptoms and
      airflow limitations or bronchial hyper-responsiveness were enrolled at 17 centers
      in South Korea. After a baseline visit, the subjects were followed up every 3
      months for various assessments. RESULTS: From June 2005 to October 2013, a total
      of 477 subjects (433 [91%] males; 381 [80%] diagnosed with COPD) were enrolled.
      Analyses of the KOLD Cohort Study identified distinct phenotypes in patients with
      COPD, and predictors of therapeutic responses and exacerbations as well as the
      factors related to pulmonary hypertension in COPD. In addition, several genotypes
      were associated with radiological phenotypes and therapeutic responses among
      Korean COPD patients. CONCLUSION: The KOLD Cohort Study is one of the leading
      long-term prospective longitudinal studies investigating heterogeneity of the
      COPD and is expected to provide new insights for pathogenesis and the long-term
      progression of COPD.

PMID- 24851131
TI  - A case of pleural paragonimiasis confused with tuberculous pleurisy.
AB  - Here, we report a case of pleural paragonimiasis that was confused with
      tuberculous pleurisy. A 38-year-old man complained of a mild febrile sensation
      and pleuritic chest pain. Radiologic findings showed right pleural effusion with
      pleural thickening and subpleural consolidation. Adenosine deaminase (ADA)
      activity in the pleural effusion was elevated (85.3 IU/L), whereas other
      examinations for tuberculosis were negative. At this time, the patient started
      empirical anti-tuberculous treatment. Despite 2 months of treatment, the pleural
      effusion persisted, and video-assisted thoracoscopic surgery was performed.
      Finally, the patient was diagnosed with pleural paragonimiasis based on the
      pathologic findings of chronic granulomatous inflammation containing Paragonimus
      eggs. This case suggested that pleural paragonimiasis should be considered when
      pleural effusion and elevated ADA levels are observed. 

PMID- 24851132
TI  - A Case of IgG4-Related Disease Presenting as Massive Pleural Effusion and
      Thrombophlebitis.
AB  - Immunoglobulin (Ig) G4-related disease is a recently recognized systemic
      fibroinflammatory condition characterized by a lymphoplasmacytic infiltrate rich
      in IgG4-positive plasma cells with elevated circulating levels of IgG4. The
      disease can either be localized to one or two organs, or present as diffuse multi
      organ disease. Furthermore, lesions in different organs can present
      simultaneously or metachronously. In the pulmonary manefestations, lesions
      associated with IgG4-related disease have been described in the lung parenchyma,
      airways and pleura, as well as the mediastinum. We report a case of IgG4-related
      disease presenting as massive pleural effusion and thrombophlebitis. 

PMID- 24851133
TI  - Single pleural relapse of a nasal-type extranodal natural killer/t-cell lymphoma:
      a case report.
AB  - A nasal-type extranodal natural killer/T-cell lymphoma is considered an
      aggressive form of non-Hodgkin's lymphoma, with approximately half of all
      patients relapsing during the follow-up period, and most relapses occurring
      within the first 2 years of remission. Here we report an unusual case of a 42
      year-old man who experienced recurrence in single pleura after 8 years of
      remission. 

PMID- 24851134
TI  - Acute eosinophilic pneumonia following secondhand cigarette smoke exposure.
AB  - Acute eosinophilic pneumonia (AEP) is a disease characterized by an acute febrile
      onset, eosinophilia in bronchoalveolar lavage fluid, and a dramatic response to
      corticosteroids. Although many studies have reported a close relationship between
      direct cigarette smoking and AEP, few studies have identified an association
      between passive smoking and AEP. Here, we report a case of AEP in a 19-year-old
      female with cough, fever, and dyspnea after 4 weeks of intense exposure to
      secondhand smoke for 6 to 8 hours a day in an enclosed area. 

PMID- 24851135
TI  - Long-term treatment with dehydroepiandrosterone may lead to follicular atresia
      through interaction with anti-Mullerian hormone.
AB  - BACKGROUND: Hyperandrogenism is the primary manifestation of polycystic ovary
      syndrome (PCOS), which appears to be caused by excess exposure to androgen. As
      such, androgenized animal models have been developed and investigated to study
      the etiology of PCOS. Anti-Mullerian hormone (AMH) is known to be associated with
      follicle growth, and its levels are two to three times higher in women with PCOS
      than in those with normal ovaries. We studied how duration of androgen
      administration affects folliculogenesis and AMH expression. METHODS: We divided
      30 immature (3-week-old) Sprague Dawley rats into six groups. Three groups were
      injected each evening with dehydroepiandrosterone (DHEA) (6 mg/100 g body
      weight/0.2 ml sesame oil) for 7, 15 or 30 days, respectively. The three control
      groups were injected with 0.2 ml of sesame oil for the corresponding lengths of
      time. Resected ovaries were sectioned and examined to determine follicle numbers
      at each developmental stage, and immunostained to assess AMH expression. RESULTS:
      On day 7, follicle numbers and AMH expression levels at each developmental stage
      of follicle growth were similar in the respective control and DHEA groups. On day
      15, the total follicle number (P = 0.041), the percentage of primordial follicles
      (P = 0.039) and AMH expression were significantly greater in the DHEA than the
      control group. On day 30, the percentages of primordial (P = 0.005), primary (P =
      0.0002) and atretic (P = 0.03) follicles were significantly greater in the DHEA
      group, whereas the percentage of intermediary follicles (early pre-antral, late
      preantral, and early antral follicles) was significantly lower in the DHEA group
      (P = <0.0001). AMH expression in DHEA-treated rats on day 30 was seen exclusively
      in the primordial (P = 0.0413) and late antral follicles (p = 0.028).
      CONCLUSIONS: Androgen administration increases AMH production in a process that
      regulates the growth of primordial follicles. That is, androgen-induced AMH
      expression provides local negative feedback to folliculogenesis augmented by
      androgen.

PMID- 24851136
TI  - Polymorphisms of VEGF and VEGF receptors are associated with the occurrence of
      ovarian hyperstimulation syndrome (OHSS)-a retrospective case-control study.
AB  - BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) is the most serious
      complication of IVF/ICSI therapy. The pathophysiology and etiology of the disease
      is still not fully clarified. METHODS: To assess whether polymorphisms of the
      VEGF/VEGF-receptor system contribute to the occurrence of ovarian
      hyperstimulation syndrome (OHSS), we performed a retrospective analysis of 116
      OHSS patients, and 124 female controls. The following SNPs were genotyped:
      Rs2071559 (VEGFR2-604); rs2305948 (VEGFR2-1192); rs1870377 (VEGFR2-1719);
      rs2010963 (VEGF-405); and rs111458691 (VEGFR1-519). Odds ratios (ORs) were
      estimated with a 95% confidence interval (CI). Linkage disequilibrium (LD)
      analysis was performed in the three loci of the VEGFR2 gene. RESULT: We found an
      overrepresentation of the T allele of the VEGFR1-519 polymorphism in OHSS
      patients (P = 0.02, OR: 3.62, CI: 1.16 - 11.27). By genotype modeling, we found
      that polymorphism of VEGFR1-519 and VEGF-405 showed significant differences in
      patients and controls (p = 0.02, OR: 3.79 CI: 1.98 - 11.97 and p = 0.000005, OR:
      0.29, CI: 0.17 - 0.50). LD analysis revealed significant linkage disequilibrium
      in VEGFR2. CONCLUSION: Polymorphisms in the VEGFR2 gene and in the VEGF gene are
      associated with the occurrence of OHSS. This strengthens the evidence for an
      important role of the VEGF/VEGF- receptor system in the occurrence of OHSS.

PMID- 24851137
TI  - Using cheminformatics to predict cross reactivity of "designer drugs" to their
      currently available immunoassays.
AB  - BACKGROUND: A challenge for drug of abuse testing is presented by 'designer
      drugs', compounds typically discovered by modifications of existing clinical drug
      classes such as amphetamines and cannabinoids. Drug of abuse screening
      immunoassays directed at amphetamine or methamphetamine only detect a small
      subset of designer amphetamine-like drugs, and those immunoassays designed for
      tetrahydrocannabinol metabolites generally do not cross-react with synthetic
      cannabinoids lacking the classic cannabinoid chemical backbone. This suggests
      complexity in understanding how to detect and identify whether a patient has
      taken a molecule of one class or another, impacting clinical care. METHODS: Cross
      reactivity data from immunoassays specifically targeting designer amphetamine
      like and synthetic cannabinoid drugs was collected from multiple published
      sources, and virtual chemical libraries for molecular similarity analysis were
      built. The virtual library for synthetic cannabinoid analysis contained a total
      of 169 structures, while the virtual library for amphetamine-type stimulants
      contained 288 compounds. Two-dimensional (2D) similarity for each test compound
      was compared to the target molecule of the immunoassay undergoing analysis.
      RESULTS: 2D similarity differentiated between cross-reactive and non-cross
      reactive compounds for immunoassays targeting mephedrone/methcathinone, 3,4
      methylenedioxypyrovalerone, benzylpiperazine, mephentermine, and synthetic
      cannabinoids. CONCLUSIONS: In this study, we applied 2D molecular similarity
      analysis to the designer amphetamine-type stimulants and synthetic cannabinoids.
      Similarity calculations can be used to more efficiently decide which drugs and
      metabolites should be tested in cross-reactivity studies, as well as to design
      experiments and potentially predict antigens that would lead to immunoassays with
      cross reactivity for a broader array of designer drugs.

PMID- 24851139
TI  - Double axis cephalocondylic fixation of stable and unstable intertrochanteric
      fractures: early results in 60 cases with the veronail system.
AB  - INTRODUCTION: This prospective case-series, without control group, study presents
      our early experience in the treatment of both stable and unstable peri
      trochanteric fractures with a new cephalocondylic implant; the Veronail system.
      MATERIALS & METHODS: Enrolment in our study was from January 2008 through
      September 2009, with follow-up until October 2011 (at least 1 year). During this
      period 65 consecutively patients with a fracture in the trochanteric region of
      the femur (31.A1, A2 and A3 according to AO classification) were surgically
      managed and prospectively followed up for at least one year. Average age was 78
      years old (range 42 to 93) with 40 female and 25 male patients. All patients were
      surgically treated using the Veronail system. Demographic and nursery data such
      as pre-existing illness, previous ambulatory status, type of anaesthesia,
      duration of surgery, volume of blood loss, transfusions, length of hospital stay,
      time to union and overall complications were systematically recorded and
      analysed. RESULTS: Mean follow up was 17 months (range, 12 to 23 months).
      Radiological evaluation was performed at 1, 3, 6 and 12 months postoperatively,
      as well as at the last follow up visit. Clinical outcome was assessed using the
      parameters of Harris Hip score. Solid union was achieved in 57/60 patients (95%)
      at a mean time of 12.5 weeks. Two fractures did not progress to union. There were
      3 superficial infections and 1 deep infection; all were successfully managed with
      appropriate antibiotic treatment. The Harris hip score at the last follow up
      visit was excellent or good in 46 (77%) of the patients. CONCLUSIONS: In the face
      of the good clinical and radiological results we consider the Veronail system to
      be of particular interest and perfectly adapted in primary surgery for both
      elderly and young patients.

PMID- 24851138
TI  - The zirconia ceramic: strengths and weaknesses.
AB  - Metal ceramic restorations were considered the gold standard as reliable
      materials. Increasing demand for esthetics supported the commercialization of new
      metal free restorations. A growing demand is rising for zirconia prostheses. Peer
      reviewed articles published till July 2013 were identified through a Medline
      (Pubmed and Elsevier). Emphasizing was made on zirconia properties and
      applications. Zirconia materials are able to withstand posterior physiologic
      loads. Although zirconia cores are considered as reliable materials, these
      restorations are not problem free. 

PMID- 24851140
TI  - Ultrasonically assisted anchoring of biodegradable implants for chevron
      osteotomies - clinical evaluation of a novel fixation method.
AB  - Reconstructive osteotomies for the treatment of Hallux valgus are among the most
      prevalent procedures in foot and ankle surgery. The combination of biodegradable
      materials with an innovative method for fixation by application of ultrasonic
      energy facilitates a new bonding method for fractures or osteotomies. As clinical
      experience is still limited, the aim of this study was to assess the safety and
      performance of the SonicPin system for fixation of Austin/Chevron osteotomies.
      Chevron osteotomy was performed on 30 patients for the treatment of Hallux
      valgus. The used SonicPins were made from polylactide and are selectively melted
      into the cancellous bone structure during insertion by ultrasonic energy.
      Patients were followed for one year, which included X-ray and MRI examinations as
      well as evaluation of life quality by EQ-5D (EuroQol). The MRI after three months
      showed adequate bone healing in all cases and no signs of foreign body reactions,
      which was again confirmed by MRI 12 months postoperatively. The bony healing
      after 12 months was uneventful without any signs of foreign body reactions. In
      summary, based on the low complication rate and the significant improvement in
      health related quality of life (EQ-5D) reported in this study, fixation of an
      Austin/Chevron osteotomy with a SonicPin for treatment of Hallux valgus can be
      considered to be safe and efficient over the short term. LEVEL OF CLINICAL
      EVIDENCE: Therapeutic Level III.

PMID- 24851141
TI  - Land System Science: between global challenges and local realities.
AB  - This issue of Current Opinion in Environmental Sustainability provides an
      overview of recent advances in Land System Science while at the same time setting
      the research agenda for the Land System Science community. Land System Science is
      not just representing land system changes as either a driver or a consequence of
      global environmental change. Land systems also offer solutions to global change
      through adaptation and mitigation and can play a key role in achieving a
      sustainable future earth. The special issue assembles 14 articles that entail
      different perspectives on land systems and their dynamics, synthesizing current
      knowledge, highlighting currently under-researched topics, exploring scientific
      frontiers and suggesting ways ahead, integrating a plethora of scientific
      disciplines.

PMID- 24851142
TI  - Familial cancer among consecutive uterine cancer patients in Sweden.
AB  - BACKGROUND: Uterine cancer (UC) represents 5.1% of all female malignancies in
      Sweden. Accumulation of UC in families occurs in around 5% of cases. We wanted to
      identify any familial association between UC and other selected cancers and to
      study the frequency of Lynch,Cowden and cancer syndromes among consecutive UC
      patients in Sweden. METHODS: 481 UC patients were included. Information on the
      cancer diagnoses of their relatives (first- (FDRs) and second-degree (SDRs)
      relatives and first cousins) was obtained. The relative frequencies of different
      cancers among relatives were compared to those in the Swedish general cancer
      population in 1970 and 2010. Families that fulfilled the criteria for hereditary
      cancer syndromes were tested for mutations in the causative genes. Families with
      at least one case of UC in addition to the index patient were compared to
      families with no additional cases to investigate possible characteristics of
      putative hereditary cancer syndromes. RESULTS: There was an increased prevalence
      of UC in our study population compared to the Swedish general cancer population
      in 1970 and 2010 (6% vs. 4% and 3%, respectively). Seven families had Lynch
      Syndrome according to the Amsterdam II criteria. No families fulfilled the
      criteria for Cowden syndrome. In total 13% of index patients had at least one
      relative with UC and these families tended to have more cases of early onset
      cancer among family members. In addition, 16% of index patients were diagnosed
      with at least one other cancer. No families fulfilled the criteria for Cowden
      syndrome. CONCLUSION: We showed a familial clustering of UC among relatives of
      our index patients. Of the seven families with mutation-verified Lynch Syndrome,
      only one had been previously diagnosed, highlighting the need to increase
      gynecologists' awareness of the importance of taking family history. Our data on
      multiple cancers and young age of onset in families with uterine cancer is
      compatible with the existence of additional hereditary uterine cancer syndromes.

PMID- 24851143
TI  - CANONICAL CORRELATION ANALYSIS BETWEEN TIME SERIES AND STATIC OUTCOMES, WITH
      APPLICATION TO THE SPECTRAL ANALYSIS OF HEART RATE VARIABILITY.
AB  - Although many studies collect biomedical time series signals from multiple
      subjects, there is a dearth of models and methods for assessing the association
      between frequency domain properties of time series and other study outcomes. This
      article introduces the random Cramer representation as a joint model for
      collections of time series and static outcomes where power spectra are random
      functions that are correlated with the outcomes. A canonical correlation analysis
      between cepstral coefficients and static outcomes is developed to provide a
      flexible yet interpretable measure of association. Estimates of the canonical
      correlations and weight functions are obtained from a canonical correlation
      analysis between the static outcomes and maximum Whittle likelihood estimates of
      truncated cepstral coefficients. The proposed methodology is used to analyze the
      association between the spectrum of heart rate variability and measures of sleep
      duration and fragmentation in a study of older adults who serve as the primary
      caregiver for their ill spouse.

PMID- 24851144
TI  - Evidence of symptom profiles consistent with posttraumatic stress disorder and
      complex posttraumatic stress disorder in different trauma samples.
AB  - BACKGROUND: The International Classification of Diseases, 11th version (ICD-11),
      proposes two related stress and trauma-related disorders, posttraumatic stress
      disorder (PTSD) and complex PTSD (CPTSD). A diagnosis of CPTSD requires that in
      addition to the PTSD symptoms, an individual must also endorse symptoms in three
      major domains: (1) affective dysregulation, (2) negative self-concepts, and (3)
      interpersonal problems. This study aimed to determine if the naturally occurring
      distribution of symptoms in three groups of traumatised individuals (bereavement,
      sexual victimisation, and physical assault) were consistent with the ICD-11,
      PTSD, and CPTSD specification. The study also investigated whether these groups
      differed on a range of other psychological problems. METHODS AND RESULTS:
      Participants completed self-report measures of each symptom group and latent
      class analyses consistently found that a three class solution was best. The
      classes were "PTSD only," "CPTSD," and "low PTSD/CPTSD." These classes differed
      significantly on measures of depression, anxiety, dissociation, sleep
      disturbances, somatisation, interpersonal sensitivity, and aggression. The
      "CPTSD" class in the three samples scored highest on all the variables, with the
      "PTSD only" class scoring lower and the "low PTSD/CPTSD" class the lowest.
      CONCLUSION: This study provides evidence to support the diagnostic structure of
      CPTSD and indicted that CPTSD is associated with a broad range of other
      psychological problems.

PMID- 24851145
TI  - Standards for endovascular neurosurgical training and certification of the
      society of korean endovascular neurosurgeons 2013.
AB  - The need for standard endovascular neurosurgical (ENS) training programs and
      certification in Korea cannot be overlooked due to the increasing number of ENS
      specialists and the expanding ENS field. The Society of Korean Endovascular
      Neurosurgeons (SKEN) Certification Committee has prepared training programs and
      certification since 2010, and the first certificates were issued in 2013. A task
      force team (TFT) was organized in August 2010 to develop training programs and
      certification. TFT members researched programs and systems in other countries to
      develop a program that best suited Korea. After 2 years, a rough draft of the ENS
      training and certification regulations were prepared, and the standard training
      program title was decided. The SKEN Certification Committee made an official
      announcement about the certification program in March 2013. The final
      certification regulations comprised three major parts: certified endovascular
      neurosurgeons (EN), certified ENS institutions, and certified ENS training
      institutions. Applications have been evaluated and the results were announced in
      June 2013 as follows: 126 members received EN certification and 55 hospitals
      became ENS-certified institutions. The SKEN has established standard ENS training
      programs together with a certification system, and it is expected that they will
      advance the field of ENS to enhance public health and safety in Korea. 

PMID- 24851146
TI  - The neuroprotective effects of carnosine in early stage of focal ischemia rodent
      model.
AB  - OBJECTIVE: This study was conducted to elucidate neuroprotective effect of
      carnosine in early stage of stroke. METHODS: Early stage of rodent stroke model
      and neuroblastoma chemical hypoxia model was established by middle cerebral
      artery occlusion and antimycin A. Neuroprotective effect of carnosine was
      investigated with 100, 250, and 500 mg of carnosine treatment. And antioxidant
      expression was analyzed by enzyme linked immunosorbent assay (ELISA) and western
      blot in brain and blood. RESULTS: Intraperitoneal injection of 500 mg carnosine
      induced significant decrease of infarct volume and expansion of penumbra
      (p<0.05). The expression of superoxide dismutase (SOD) showed significant
      increase than in saline group in blood and brain (p<0.05). In the analysis of
      chemical hypoxia, carnosine induced increase of neuronal cell viability and
      decrease of reactive oxygen species (ROS) production. CONCLUSION: Carnosine has
      neuroprotective property which was related to antioxidant capacity in early stage
      of stroke. And, the oxidative stress should be considered one of major factor in
      early ischemic stroke.

PMID- 24851147
TI  - Targeting Orthotopic Glioma in Mice with Genetically Engineered Salmonella
      typhimurium.
AB  - OBJECTIVE: With the growing interests of bacteria as a targeting vector for
      cancer treatment, diverse genetically engineered Salmonella has been reported to
      be capable of targeting primary or metastatic tumor regions after intravenous
      injection into mouse tumor models. The purpose of this study was to investigate
      the capability of the genetically engineered Salmonella typhimurium (S.
      typhimurium) to access the glioma xenograft, which was monitored in mouse brain
      tumor models using optical bioluminescence imaging technique. METHODS: U87
      malignant glioma cells (U87-MG) stably transfected with firefly luciferase (Fluc)
      were implanted into BALB/cAnN nude mice by stereotactic injection into the
      striatum. After tumor formation, attenuated S. typhimurium expressing bacterial
      luciferase (Lux) was injected into the tail vein. Bioluminescence signals from
      transfected cells or bacteria were monitored using a cooled charge-coupled device
      camera to identify the tumor location or to trace the bacterial migration.
      Immunofluorescence staining was also performed in frozen sections of mouse glioma
      xenograft. RESULTS: The injected S. typhimurium exclusively localized in the
      glioma xenograft region of U87-MG-bearing mouse. Immunofluorescence staining also
      demonstrated the accumulation of S. typhimurium in the brain tumors. CONCLUSION:
      The present study demonstrated that S. typhimurium can target glioma xenograft,
      and may provide a potentially therapeutic probe for glioma.

PMID- 24851148
TI  - Reliability of stereotactic coordinates of 1.5-tesla and 3-tesla MRI in
      radiosurgery and functional neurosurgery.
AB  - OBJECTIVE: The aims of this study are to identify interpersonal differences in
      defining coordinates and to figure out the degree of distortion of the MRI and
      compare the accuracy between CT, 1.5-tesla (T) and 3.0T MRI. METHODS: We compared
      coordinates in the CT images defined by 2 neurosurgeons. We also calculated the
      errors of 1.5T MRI and those of 3.0T. We compared the errors of the 1.5T with
      those of the 3.0T. In addition, we compared the errors in each sequence and in
      each axis. RESULTS: The mean difference in the CT images between the two
      neurosurgeons was 0.48+/-0.22 mm. The mean errors of the 1.5T were 1.55+/-0.48 mm
      (T1), 0.75+/-0.38 (T2), and 1.07+/-0.57 (FLAIR) and those of the 3.0T were 2.35+/
      0.53 (T1), 2.18+/-0.76 (T2), and 2.16+/-0.77 (FLAIR). The smallest mean errors
      out of all the axes were in the x axis : 0.28-0.34 (1.5T) and 0.31-0.52 (3.0T).
      The smallest errors out of all the MRI sequences were in the T2 : 0.29-0.58
      (1.5T) and 0.31-1.85 (3.0T). CONCLUSION: There was no interpersonal difference in
      running the Gamma Plan(r) to define coordinates. The errors of the 3.0T were
      greater than those of the 1.5T, and these errors were not of an acceptable level.
      The x coordinate error was the smallest and the z coordinate error was the
      greatest regardless of the MRI sequence. The T2 sequence was the most accurate
      sequence.

PMID- 24851149
TI  - Comparison of Clinical and Radiologic Results between Expandable Cages and
      Titanium Mesh Cages for Thoracolumbar Burst Fracture.
AB  - OBJECTIVE: A thoracolumbar burst fracture is usually unstable and can cause
      neurological deficits and angular deformity. Patients with unstable thoracolumbar
      burst fracture usually need surgery for decompression of the spinal canal,
      correction of the angular deformity, and stabilization of the spinal column. We
      compared two struts, titanium mesh cages (TMCs) and expandable cages. METHODS: 33
      patients, who underwent anterior thoracolumbar reconstruction using either TMCs
      (n=16) or expandable cages (n=17) between June 2000 and September 2011 were
      included in this study. Clinical outcome was measured by visual analogue scale
      (VAS), American Spinal Injury Association (ASIA) scale and Low Back Outcome Score
      (LBOS) for functional neurological evaluation. The Cobb angle, body height of the
      fractured vertebra, the operation time and amount of intra-operative bleeding
      were measured in both groups. RESULTS: In the expandable cage group, operation
      time and amount of intraoperative blood loss were lower than that in the TMC
      group. The mean VAS scores and LBOS in both groups were improved, but no
      significant difference. Cobb angle was corrected higher than that in expandable
      cage group from postoperative to the last follow-up. The change in Cobb angles
      between preoperative, postoperative, and the last follow-up did not show any
      significant difference. There was no difference in the subsidence of anterior
      body height between both groups. CONCLUSION: There was no significant difference
      in the change in Cobb angles with an inter-group comparison, the expandable cage
      group showed better results in loss of kyphosis correction, operation time, and
      amount of intraoperative blood loss.

PMID- 24851150
TI  - Clinical features of wrist drop caused by compressive radial neuropathy and its
      anatomical considerations.
AB  - OBJECTIVE: Posture-induced radial neuropathy, known as Saturday night palsy,
      occurs because of compression of the radial nerve. The clinical symptoms of
      radial neuropathy are similar to stroke or a herniated cervical disk, which makes
      it difficult to diagnose and sometimes leads to inappropriate evaluations. The
      purpose of our study was to establish the clinical characteristics and diagnostic
      assessment of compressive radial neuropathy. METHODS: Retrospectively, we
      reviewed neurophysiologic studies on 25 patients diagnosed with radial nerve
      palsy, who experienced wrist drop after maintaining a certain posture for an
      extended period. The neurologic presentations, clinical prognosis, and
      electrophysiology of the patients were obtained from medical records. RESULTS:
      Subjects were 19 males and 6 females. The median age at diagnosis was 46 years.
      The right arm was affected in 13 patients and the left arm in 12 patients. The
      condition was induced by sleeping with the arms hanging over the armrest of a
      chair because of drunkenness, sleeping while bending the arm under the pillow,
      during drinking, and unknown. The most common clinical presentation was a wrist
      drop and paresthesia on the dorsum of the 1st to 3rd fingers. Improvement began
      after a mean of 2.4 weeks. Electrophysiologic evaluation was performed after 2
      weeks that revealed delayed nerve conduction velocity in all patients.
      CONCLUSION: Wrist drop is an entrapment syndrome that has a good prognosis within
      several weeks. Awareness of its clinical characteristics and diagnostic
      assessment methods may help clinicians make diagnosis of radial neuropathy and
      exclude irrelevant evaluations.

PMID- 24851151
TI  - Brainstem Congestion due to Dural Ateriovenous Fistula at the Craniocervical
      Junction.
AB  - Dural ateriovenous fistula (DAVF) at the craniocervical junction is rare. We
      report a patient presenting with brainstem dysfunction as an uncommon onset.
      Brainstem lesion was suggested by magnetic resonance image study. Angiogram
      revealed a DAVF at a high cervical segment supplied by the meningeal branch of
      the right vertebral artery, with ascending and descending venous drainage.
      Complete obliteration of the fistula was achieved via transarterial Onyx
      embolization. Clinical cure was achieved in the follow-up period; meanwhile,
      imaging abnormalities of this case disappeared. Accordingly, we hypothesize that
      a brainstem lesion of this case was caused by craniocervical DAVF, which induced
      venous hypertension. Thus, venous drainage patterns should be paid attention to
      because they are important for diagnosis and theraputic strategy. 

PMID- 24851152
TI  - Paraplegia due to Acute Aortic Coarctation and Occlusion.
AB  - Coarctation and occlusion of the aorta is a rare condition that typically
      presents with hypertension or cardiac failure. However, neuropathy or myelopathy
      may be the presenting features of the condition when an intraspinal subarachnoid
      hemorrhage has compressed the spinal cord causing ischemia. We report two cases
      of middle-aged males who developed acute non-traumatic paraplegia. Undiagnosed
      congenital abnormalities, such as aortic coarctation and occlusion, should be
      considered for patients presenting with nontraumatic paraplegia in the absence of
      other identifiable causes. Our cases suggest that spinal cord ischemia resulting
      from acute spinal subarachnoid hemorrhage and can cause paraplegia, and that
      clinicians must carefully examine patients presenting with nontraumatic
      paraplegia because misdiagnosis can delay initiation of the appropriate
      treatment. 

PMID- 24851153
TI  - Large intracranial aneurysm after transsphenoidal surgery for pituitary
      macroadenoma.
AB  - Uncontrolled cerebrospinal fluid (CSF) leakage after transsphenoidal surgery
      (TSS) for pituitary adenoma can lead to meningitis. Intracranial mycotic
      pseudoaneurysm is a rare complication in central nervous system infection. Large
      single pseudoaneurysm is more uncommon. Most mycotic aneurysms occur due to
      endocarditis. The present patient had no heart problem and was infected by CSF
      leakage after transsphenoidal surgery. We present a case of large ruptured
      mycotic pseudoaneurysm as a complication of cerebral infection after TSS for
      pituitary macroadenoma. 

PMID- 24851154
TI  - Ganglioglioma in brainstem : case report and a review of literatures.
AB  - Ganglioglioma is an infrequent tumor of the central nervous system (CNS); mostly
      supratentorial region. But, they can occur anywhere in the central nervous system
      such as brainstem, cerebellopontine angle (CPA), thalamus, optic nerve and spinal
      cord. Although it occurs rarely, ganglioglioma should be included in the
      differential diagnosis of a posterior fossa mass because early recognition is
      important for treatment and patient counseling. 

PMID- 24851155
TI  - Giant cell tumor of upper thoracic spine.
AB  - Giant cell tumor (GCT) of the spine is a rare benign tumor, but can be aggressive
      and can exhibit a high local recurrence rate. Furthermore, GCT of the upper
      thoracic spine may pose diagnostic and management difficulties. Here, we report a
      rare case of GCT of the upper thoracic spine with soft tissue extension to the
      spinal canal. The patient was managed by decompressive laminectomy and
      posterolateral fusion followed by an injection of polymethylmethacrylate into the
      vertebral lesion. The patient recovered clinically and showed radiological
      improvement after surgical treatment without tumor recurrence at his last follow
      up of postoperative 7 years. We present this unusual case of GCT and include a
      review of the literature. 

PMID- 24851156
TI  - Unintended complication of intracranial subdural hematoma after percutaneous
      epidural neuroplasty.
AB  - Percutaneous epidural neuroplasty (PEN) is a known interventional technique for
      the management of spinal pain. As with any procedures, PEN is associated with
      complications ranging from mild to more serious ones. We present a case of
      intracranial subdural hematoma after PEN requiring surgical evacuation. We review
      the relevant literature and discuss possible complications of PEN and
      patholophysiology of intracranial subdural hematoma after PEN. 

PMID- 24851157
TI  - Emergency neuroendoscopic management of third ventricular neurocysticercosis cyst
      presented with bruns syndrome : report of two cases and review of literature.
AB  - Neurocysticercosis is the commonest parasitic disease of the human central
      nervous system. The incidence of intra ventricular form of neurocysticercosis
      (NCC) is less common accounting 10-20% that of total central nerve system
      cysticercosis. Intra ventricular NCC is complicated due, to its high incidence of
      acute hydrocephalus caused by ball valve mechanism. The only reliable tool for
      diagnosis of NCC is by neuroimaging with CT or MRI. MRI preferred over CT because
      of its high specificity and sensitivity. In emergency situations like acute
      hydrocephalus one can proceed with emergency endoscopic surgery. Through the
      endoscopic view, intra ventricular NCC (IVNCC) has distinguished morphological
      features like the full moon sign. This feature not only helps in identification
      of IVNCC, but also guides in further endoscopic treatment strategy. Authors
      report two cases of 3rd ventricular NCC with acute hydrocephalus managed with
      emergency endoscopy. Authors have discussed the clinical features, intra
      operative endoscopic findings and role of endoscopy in emergency surgery for NCC
      with acute hydrocephalus. 

PMID- 24851158
TI  - Management of otogenic brain abscess using the transmastoid approach.
AB  - Despite significant advances in the treatment of all forms of chronic otitis
      media (COM), complications still can and do occur, with intracranial
      complications representing the most life-threatening cases, often requiring
      immediate therapeutic intervention. Herein, we present a rare case of rapidly
      progressing facial paralysis with concomitant severe headache and ipsilateral
      hearing loss secondary to an otogenic brain abscess, treated with the
      transmastoid approach, drainage, and facial nerve decompression. 

PMID- 24851159
TI  - Could this be another story of montage?

PMID- 24851160
TI  - Comparison of bispectral index scores from the standard frontal sensor position
      with those from an alternative mandibular position.
AB  - BACKGROUND: The standard bifrontal application of the bispectral index (BIS)
      sensor interferes with the operative field in neurosurgery and plastic surgery.
      The aim of this study was to compare the standard frontal BIS sensor position
      with an alternative position across the mandible. METHODS: Two BISTM Quatro
      sensors (Aspect Medical Systems, Newton, MA, USA) mounted on the frontal and
      mandibular regions were connected to BIS VistaTM monitors on each patient during
      general anesthesia. Data from each position were collected at awake, loss of
      consciousness, intubation, incision, every 30 minutes during the intraoperative
      period and emergence. These data were compared using Bland-Altman and scatter
      plot analyses. RESULTS: Scatter plot analysis revealed a significant correlation
      between BIS values of frontal and mandibular positions (R = 0.869, P = 0.000),
      except during emergence (R = 0.253, P = 0.077). Bland-Altman analysis revealed a
      negative bias of 3.2 with a limit of agreement of 16.5/-22.9, in which 3.7% of
      the values were outside of the limit of agreement. Additional values included 
      2.9 (14.1/-8.3) while patients were awake, -21.7 (14.9/-58.3) at loss of
      consciousness, -1.8 (9.0/-12.5) during maintenance, and -1.9 (14.9/-18.8) during
      emergence. CONCLUSIONS: Overall, BIS values do not agree between the standard
      frontal position and an alternative mandibular position. However, during the
      anesthesia maintenance period, the mandibular position can be availably used as
      an alternative position if the operative field renders the standard frontal
      position unavailable.

PMID- 24851161
TI  - End-tidal concentration of sevoflurane for preventing rocuronium-induced
      withdrawal of the arm in pediatric patients.
AB  - BACKGROUND: During induction of general anesthesia, the intravenous injection of
      rocuronium is often associated with withdrawal movement of the arm due to pain,
      and this abrupt withdrawal may result in dislodgement of the venous catheter,
      injury, or inadequate injection of rocuronium. We performed this study to
      evaluate the 50 and 95% effective end-tidal concentrations of sevoflurane (ETsev)
      for preventing rocuronium-induced withdrawal of the arm. METHODS: We conducted a
      prospective double-blind study in 31 pediatric patients. After free flow of
      lactated Ringer's IV fluid was confirmed, anesthesia was induced in the patients
      by using 2.5% thiopental sodium (4 mg/kg) and sevoflurane (4 vol%) with 6 L/min
      of oxygen. When the target ETsev was reached, preservative-free 1% lidocaine (1.5
      mg/kg) was intravenously injected during manual venous occlusion and rocuronium
      (0.6 mg/kg) was injected after lidocaine injection under free-flow intravenous
      fluid. A nurse who was an investigator and was blinded to the ETsev injected the
      rocuronium. The nurse evaluated the response. RESULTS: Non-withdrawal movement
      was observed in 5 out of 11 patients with ETsev 3.0 vol% and in 5 out of 6
      patients with ETsev 3.5 vol%. By Dixon's up-and-down method, the 50% effective
      concentration (EC50) of sevoflurane for non-withdrawal movement at rocuronium
      injection was 3.1 +/- 0.4 vol%. A logistic regression curve of the probability of
      non-withdrawal movements showed that the 50% effective ETsev for abolishing
      withdrawal movement at rocuronium injection was 2.9 vol% (95% confidence interval
      [CI] 2.4-3.8 vol%) and the 95% effective ETsev was 4.3 vol% (95% CI 3.6-9.8
      vol%). CONCLUSIONS: This study showed that the 50 and 95% effective ETsev that
      prevent withdrawal movement at rocuronium injection are 2.9 and 4.3 vol%,
      respectively.

PMID- 24851162
TI  - Remifentanil dose for laryngeal mask airway insertion with a single standard dose
      of propofol during emergency airway management in elderly patients.
AB  - BACKGROUND: This study determined the dose of remifentanil to use during
      insertion of a ClassicTM laryngeal mask airway (LMA, The Laryngeal Mask Co.,
      Nicosia, Cyprus) in elderly patients during emergency airway management when
      combined with a single dose of propofol. METHODS: Patients aged 65-80 years were
      enrolled. Anesthesia was induced with propofol 1 mg/kg, and then a blinded dose
      of remifentanil was infused over 30 s after confirming the patient's loss of
      consciousness. The dose of remifentanil was determined using Dixon's up-and-down
      method, starting at 0.5 ug/kg (a step size of 0.1 ug/kg). Insertion of the LMA
      was attempted 60 s after loss of consciousness. RESULTS: In total, 23 patients
      were recruited and the mean age +/- standard deviation was 72 +/- 3 years. The
      effective dose for successful LMA insertion in 50% of the patients (ED50) was
      0.20 +/- 0.05 ug/kg. No patient needed more than 0.3 ug/kg. CONCLUSIONS:
      Remifentanil 0.20 +/- 0.05 ug/kg with propofol 1 mg/kg resulted in excellent LMA
      insertion in 50% of elderly patients without significant hemodynamic changes
      during emergency airway management.

PMID- 24851163
TI  - Comparison of dexmedetomidine and epinephrine as an adjuvant to 1% mepivacaine in
      brachial plexus block.
AB  - BACKGROUND: Dexmedetomidine extends the duration of nerve block when administered
      perineurally together with local anesthetics by central and/or peripheral action.
      In this study, we compared the duration of nerve block between dexmedetomidine
      and epinephrine as an adjuvant to 1% mepivacaine in infraclavicular brachial
      plexus block. METHODS: Thirty patients, scheduled for upper limb surgery were
      assigned randomly to 3 groups of 10 patients each. We performed brachial plexus
      block using a nerve stimulator. In the control group (group C), patients received
      40 ml of 1% mepivacaine. In group E, patients received 40 ml of 1% mepivacaine
      containing 200 ug of epinephrine as an adjuvant. In group D, patients received 40
      ml of 1% mepivacaine containing 1 ug/kg of dexmedetomidine as an adjuvant.
      Sensory block duration, motor block duration, time to sense pain, and onset time
      were assessed. We also monitored blood pressure, heart rate, oxygen saturation
      and bispectral index. RESULTS: In group D and group E, sensory block duration,
      motor block duration and time to sense first pain were prolonged significantly
      compared to group C. However, there was no significant difference between group D
      and group E. CONCLUSIONS: Perineural 1 ug/kg of dexmedetomidine similarly
      prolonged nerve block duration compared to 200 ug of epinephrine, but slowed
      heart rate. Thus, dexmedetomidine is expected to be a good alternative as an
      adjuvant to local anesthesia in patients who are cautioned against epinephrine.

PMID- 24851164
TI  - Sevoflurane versus propofol for interventional neuroradiology: a comparison of
      the maintenance and recovery profiles at comparable depths of anesthesia.
AB  - BACKGROUND: Sevoflurane and propofol are used widely for interventional
      neuroradiology (INR). Using the bispectral index (BIS), we compared the clinical
      properties of sevoflurane and propofol anesthesia in patients undergoing INR at
      comparable depths of anesthesia. METHODS: The patients were allocated randomly
      into two groups. The sevoflurane group received propofol (1.5 mg/kg), alfentanil
      (5 ug/kg), and rocuronium (0.6 mg/kg) for induction, and the propofol group was
      induced with a target effect-site concentration of propofol (4 ug/ml), alfentanil
      (5 ug/kg), and rocuronium (0.6 mg/kg). After intubation, anesthesia was
      maintained with sevoflurane or propofol with 67% nitrous oxide in 33% oxygen.
      Sevoflurane and propofol concentrations were titrated to maintain the BIS at 50
      60. Phenylephrine or opioid was used to maintain the mean arterial pressure
      within 20% of the baseline values. The amounts of phenylephrine or alfentanil
      used, the number of patients showing movement during the procedure, and the
      recovery times were recorded. RESULTS: Compared to the propofol group, the
      sevoflurane group showed faster recovery in spontaneous ventilation, eye opening,
      extubation, and orientation (4 vs. 7 min, 7 vs. 9 min, 8 vs. 10 min, 10 vs. 14
      min, respectively; P < 0.01). In the propofol group, significantly greater
      amounts phenylephrine were used (P < 0.05), and more patients moved during the
      procedure (P < 0.05). CONCLUSIONS: The use of sevoflurane in maintaining
      anesthesia during INR was associated with faster recovery, less patient movement
      during the procedure, and a more stable hemodynamic response when compared to
      propofol.

PMID- 24851165
TI  - Multidrug-resistant Acinetobacter baumannii infection in intensive care unit
      patients in a hospital with building construction: is there an association?
AB  - BACKGROUND: Acinetobacter baumannii (A. baumannii) has emerged globally as a
      significant pathogen in hospitals. It is also present in soil and water. In a
      previous study, we discovered that the A. baumannii class 2 integron occurred
      most frequently. Here, we determined whether the A. baumannii class 2 integron is
      in the soil around our hospital, and if the soil is the cause for increasing
      numbers of A. baumannii infections in our intensive care unit (ICU) patients.
      METHODS: This cross-sectional prospective study was conducted in two ICUs at
      Loghman-Hakim Hospital, Tehran, Iran, from November 2012 to March 2013. Patient,
      soil, and hospital environment samples were collected. All isolates were
      identified using standard bacteriologic and biochemical methods. The phenotypes
      and genotypes were characterized. The standard disc diffusion method was utilized
      to test antimicrobial susceptibility. Integron identification was performed by
      multiplex polymerase chain reaction. RESULTS: A total of 42 A. baumannii clinical
      strains were isolated, all from patient samples; 65% of the isolated species were
      classified as class 2 integrons. The strains were 100% resistant to piperacillin,
      piperacillin-tazobactam, ceftazidime, ceftriaxone, cotrimoxazole, cefepime,
      ceropenem, and cefotaxime. However, all of the strains were sensitive to
      polymyxin B. A. baumannii was detected around the lip of one patient.
      CONCLUSIONS: Further research is necessary to establish a relationship between A.
      baumannii and soil, (especially in regards to its bioremediation), as well as to
      determine its importance in nosocomial infections and outbreaks in the ICU.

PMID- 24851166
TI  - Arrangements of the intravenous parallel infusions with anti-reflux valves
      decreasing occlusion alarm delay.
AB  - BACKGROUND: The methods of arrangement of combined intravenous parallel infusions
      using anti-reflux valve (ARV), with and without anti-syphon valve (ASV) that
      could decrease occlusion alarm delay were investigated. METHODS: Occlusion
      challenge tests were mainly performed as bench experiments of four kinds of
      multiple parallel infusions (10 ml/h and 50 ml/h infusions), which were connected
      at the proximal or distal portion of ARV, with or without ASV. Alarm threshold
      was set to 1000 mmHg. Occlusion alarm delays and the compliances of the infusion
      systems were compared among groups. RESULTS: Without ASV, compared to 10 ml/h
      infusion alone distal to anti-reflux valve, 50 ml/h infusion distal to anti
      reflux valve reduced the mean alarm delay from 416 +/- 7 s to 81 +/- 3 s (P <
      0.001). Compared to 50 ml/h infusion alone, combined 10 ml/h and 50 ml/h infusion
      distal to ARV prolonged the alarm delay from 81 +/- 3 s to 133 +/- 6 s (P <
      0.001). However, combined infusions distal to ARV with ASV significantly reduced
      the alarm delay from 133 +/- 6 s to 74 +/- 5 s (P < 0.001), and also reduced the
      compliance of the infusion system from 2.31 +/- 0.12 to 1.20 +/- 0.08 ul/mmHg (P
      < 0.001). CONCLUSIONS: The infusion setup of faster infusion rate, lower
      compliant system using ASV could effectively decrease occlusion alarm delay
      during multiple intravenous parallel infusions using ARV.

PMID- 24851167
TI  - Videothoracoscopic management of a perforated central vein and pleura after
      ultrasound-guided internal jugular vein cannulation: a case report.
AB  - A 23-year-old male underwent a left internal jugular vein catheterization during
      extended surgery for treatment of multiple fractures due to a traffic accident.
      Although the catheterization was performed under ultrasound (US) guidance,
      iatrogenic perforation of the central vein and pleura occurred. The catheter was
      removed, and the perforated site was addressed under thoracoscopy rather than an
      open thoracotomy. This case suggests that using US does not completely guarantee
      a complication-free outcome, and that catheter placement should be carefully
      confirmed. In addition, this case suggests that thoracoscopy may be an ideal
      method of resolving a perforation of the central vein and pleura. 

PMID- 24851168
TI  - Combined use of a McGrath(r) MAC video laryngoscope and Frova Intubating
      Introducer in a patient with Pierre Robin syndrome: a case report.
AB  - Patients with Pierre Robin syndrome are characterized by micrognathia,
      retrognathia, glossoptosis, and respiratory obstruction and are prone to have a
      difficult-to-intubate airway. The McGrath(r) MAC video laryngoscope provides a
      better view of the glottis than a Macintosh laryngoscope, but it is not easy to
      insert an endotracheal tube through the vocal cords because a video laryngoscope
      has a much greater curvature than that of a conventional direct laryngoscope and
      an endotracheal tube has a different curvature. The Frova Intubating Introducer
      is used as a railroad for an endotracheal tube in cases of a difficult airway. We
      thought that a combination of these two devices would make it easy to insert an
      endotracheal tube through the vocal cords, as a McGrath(r) MAC video laryngoscope
      provides a better glottic view and the Frova Intubating Introducer is a useful
      device for placing an endotracheal tube through the glottis. We report a
      successful endotracheal intubation with use of the McGrath(r) MAC video
      laryngoscope and Frova Intubating Introducer in a patient with Pierre Robin
      syndrome. 

PMID- 24851169
TI  - Echocardiographic detection of left atrial mobile calcium debris of trido valve
      surgery: a case report.
AB  - Calcification of the cardiac chambers is among the challenges associated with
      reoperative cardiac surgeries by increasing the risk of systemic embolization. We
      experienced a case of an unexpected detected mass by intraoperative
      transesophageal echocardiography during weaning from cardiopulmonary bypass in a
      patient undergoing trido mitral and tricuspid valve replacement surgery. The
      surgically removed mass was identified as calcified tissue. This case shows the
      importance of careful echocardiographic evaluation of the left heart in patients
      undergoing repeat valve surgery given their greater potential for embolic
      sources. 

PMID- 24851170
TI  - Monitored anesthesia care with dexmedetomidine in transfemoral percutaneous trans
      catheter aortic valve implantation: two cases report.
AB  - Percutaneous trans-catheter aortic valve implantation (TAVI) is recommended for
      inoperable patients with severe aortic stenosis at high risk for conventional
      aortic valve replacement. Originally, TAVI was mostly performed under general
      anesthesia. Here we describe two cases of transfemoral TAVI performed under
      monitored anesthesia care (MAC) with dexmedetomidine. Dexmedetomidine provides
      sedation, analgesia with minimal respiratory depression. Although MAC during
      transfemoral TAVI has limitations, such as unexpected patient movement and
      difficulty in intra-procedural use of transesophageal echocardiography, MAC with
      dexmedetomidine is feasible with close monitoring, fluoroscopic guidance and the
      participation of experienced anesthesiologists. 

PMID- 24851171
TI  - Anesthesia for non-pulmonary surgical intervention following lung
      transplantation: two cases report.
AB  - The survival rate after lung transplantation has increased in recent years,
      leading to an increase in non-pulmonary conditions that require surgical
      intervention. These post-transplant surgical procedures, however, are associated
      with high mortality and morbidity rates. Intra-abdominal conditions are the most
      common reasons for surgical intervention. We describe here two patients who
      underwent abdominal surgery under general anesthesia following lung
      transplantation. One patient underwent cholecystectomy due to cholecystitis after
      heart-lung transplantation, and the other patient had an exploratory laparotomy
      for duodenal ulcer perforation after double lung transplantation. Depending on
      the type of transplant intervention, the physiology of the transplanted lung must
      be considered for general anesthesia. Knowledge of underlying conditions and
      immunosuppressive therapy following transplantation are important for safe and
      effective general anesthesia. 

PMID- 24851172
TI  - Effects of palonosetron on prolongation of corrected QT intervals may be less
      than reliable.

PMID- 24851173
TI  - Application of 3D Ultrasonography in Detection of Uterine Abnormalities.
AB  - Structural pathologies in the uterine cavity such as mullerian duct anomalies
      (MDAs) and intrauterine lesions (fibroids, polyps, synechiae) may have important
      roles in subinfertility, implantation failure and pregnancy outcome. Various
      imaging modalities such as hysterosalpingography (HSG), sonography, laparoscopy
      and hysteroscopy are used in the evaluation of MDAs and intrauterine lesions.
      Recently, three-dimensional ultrasound (3DUS) has been introduced as a non
      invasive, outpatient diagnostic modality. With increased spatial awareness, it is
      superior to other techniques used for the same purpose. 

PMID- 24851174
TI  - Developmental Competence and Pluripotency Gene Expression of Cattle Cloned
      Embryos Derived from Donor Cells Treated with 5-aza-2'-deoxycytidine.
AB  - BACKGROUND: Reconstructed embryos from terminally differentiated somatic cells
      have revealed high levels of genomic methylation which results in inappropriate
      expression patterns of imprinted and non-imprinted genes. These aberrant
      expressions are probably responsible for different abnormalities during the
      development of clones. Improvement in cloning competency may be achieved through
      modification of epigenetic markers in donor cells. MATERIALS AND METHODS: Our
      objective was to determine if treatment of donor cells for 72 hours with 5-aza-2'
      deoxycytidine (5-aza-dc; 0-0.3 MUM), a DNA methyl transferase inhibitor, improved
      development and expression of Oct-4. RESULTS: In comparison with untreated cells,
      0.01 and 0.08 MUM 5-aza-dc treated cells insignificantly decreased the blastocyst
      rate (32.1% vs. 28.6% and 27.2%, respectively) while it was significant for 0.3
      MUM treated cells (6.5%). Embryo quality as measured by the total cell number
      (TCN) decreased in a dose-related fashion, which was significant at 0.08 and 0.3
      MUM 5-aza-dc treated cells when compared with 0 and 0.01 MUM 5-aza-dc treated
      cells. Although reconstructed embryos from 0.08 and 0.3 MUM 5-aza-dc treated
      cells showed lower levels of DNA methylation and histone H3 acetylation,
      development to blastocyst stage was decreased. The epigenetic markers of embryos
      cloned from 0.01 MUM 5-aza-dc remained unchanged. CONCLUSION: These results show
      that 5-aza-dc is not a suitable choice for modifying nuclear reprogramming.
      Finally, it was concluded that the wide genomic hypomethylation induced by 5-aza
      dc deleteriously impacts the developmental competency of cloned embryos.

PMID- 24851175
TI  - The Prevalence of Polycystic Ovary Syndrome (PCOS) in High School Students in
      Rasht in 2009 According to NIH Criteria.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common endocrine
      disorder in women associated with many reproductive, endocrine, metabolic and
      cardiovascular dysfunctions. This study aimed to determine the prevalence of PCOS
      among high school students in Rasht. MATERIALS AND METHODS: In a cross-sectional
      study, 1850 students were selected by a multi-stage cluster sampling from all
      high schools in Rasht. The inclusion criteria were: age 17-18 years, menarche
      from 10-16 years, normal prolactin and thyroid stimulating hormone (TSH) values,
      no history of anatomical malformation, no use of medication or hair-removal
      techniques, and a history of oligo- or amenorrhea. PCOS was diagnosed if both
      menstrual dysfunction and clinical hyperandrogenism were detected. RESULTS: Mean
      age of subjects was 17.2 +/- 0.7 years and the age of menarche was 12.8 +/- 0.9
      years. Of all students, 378 (20.4%) had oligomenorrhea and PCOS was diagnosed in
      210 (11.34 %) according to the National Institute of Health (NIH) definition.
      PCOS subjects, mean body mass index (BMI), waist circumference, and waist/hip
      (W/H) ratio were 21.1 +/- 3.6, 73.4 +/- 8.0 cm and 0.77 +/- 0.05, respectively. A
      family history of diabetes mellitus type 2 was reported in 24.7% of subjects.
      CONCLUSION: The prevalence of PCOS in this study was similar to the international
      estimates of 10-20% in Caucasians. A long-term follow-up is needed to compare the
      accuracy of clinical determination of the disease versus diagnosis based on
      hormonal and/or sonographic assessments.

PMID- 24851176
TI  - Improvement of Semen Quality in Holstein Bulls during Heat Stress by Dietary
      Supplementation of Omega-3 Fatty Acids.
AB  - BACKGROUND: Long-chain polyunsaturated fatty acids (PUFAs) of the omega-3 family
      are important for sperm membrane integrity, sperm motility and viability. There
      are evidences to suggest that dietary supplementation with omega-3 fatty acids
      affects reproduction in men and males of different animal species. Therefore, the
      aim of current study was to investigate changes in the quality parameters of
      Holstein bull semen during heat stress and the effect of feeding a source of
      omega-3 fatty acids during this period. MATERIALS AND METHODS: Samples were
      obtained from 19 Holstein bulls during the expected time of heat stress in Iran
      (June to September 2009). Control group (n=10) were fed a standard concentrate
      feed while the treatment group (n=9) had this feed top dressed with 100 g of an
      omega-3 enriched nutriceutical. Semen volume, sperm concentration and total sperm
      production were evaluated on ejaculates collected after 1, 5, 9 and 12 weeks of
      supplementation. Moreover, computer-assisted assessment of sperm motility,
      viability (eosin-nigrosin) and hypo-osmotic swelling test (HOST) were conducted.
      RESULTS: Heat stress affected sperm quality parameters by weeks five and nine of
      the study (p<0.05). Supplementation significantly increased total motility,
      progressive motility, HOST-positive spermatozoa and average path velocity in the
      fresh semen of bulls (p<0.05). CONCLUSION: Dietary omega-3 supplementation
      improved in vitro quality and motility parameters of fresh semen in Holstein
      bulls. However, this effect was not evident in frozen-thawed semen.

PMID- 24851177
TI  - Evaluation of homocysteine levels in patients with polycystic ovarian syndrome.
AB  - BACKGROUND: To determine the level of plasma homocysteine in patients with
      polycystic ovary syndrome (PCOS) compared with healthy controls. MATERIALS AND
      METHODS: In this prospective case-control study on 85 PCOS women and 83 controls
      matched by body mass index (BMI), homocysteine levels were assessed. RESULTS: The
      mean level of homocysteine was 16.25 +/- 11.94 MUmol/L in patients with PCOS and
      11.58 +/- 3.82 MUmol/L in controls (p=0.002). Patients with PCOS had a
      significantly higher risk for hyperhomocysteinemia compared with BMI-matched
      control women. CONCLUSION: These data suggest that homocysteine levels are
      elevated in the PCOS population. Further studies are needed to characterize this
      relationship.

PMID- 24851178
TI  - Effect of ovarian cyclic status on in vitro embryo production in cattle.
AB  - BACKGROUND: The relationship between cyclic status of cattle ovaries on in vitro
      embryo development up to the blastocyst stage was investigated. MATERIALS AND
      METHODS: Cattle ovaries were collected immediately after slaughter and divided
      into three categories based on their cyclic status, which included: 1. the
      presence of a large follicle (LF), 2. the presence of a corpus luteum (CL) and 3.
      ovaries without LF or CL (WLCF). Oocytes of these ovaries were obtained and used
      for in vitro maturation and fertilization. Presumptive zygotes were then cultured
      up to the blastocyst stage in synthetic oviductal fluid culture medium. RESULTS:
      There were no significant differences between cleavage rates of the three groups.
      The rate of embryos in the compact morula stage for the CL group was 48.2% which
      was significantly higher than the related rate of the LF group (36.6%), but non
      significantly higher than that of the ST group (45.7%). The highest blastocyst
      rate belonged to the CL group (54.6%) which was significantly greater than the
      WLCF group (32.9%) and non-significantly higher than the LF group (52.4%). There
      was no significant difference in blastocyst rates in the CL and LF groups.
      CONCLUSION: Preselection of oocyte donor ovaries containing a CL or LF can be
      used as a feasible and non- invasive criterion to obtain the most competent
      oocytes capable of development to the blastocyst stage.

PMID- 24851179
TI  - Gamete and embryo donation and surrogacy in australia: the social context and
      regulatory framework.
AB  - The social and legal acceptability of third-party reproduction varies around the
      world. In Australia, gamete and embryo donation and surrogacy are permitted
      within the regulatory framework set out by federal and state governments. The aim
      of this paper is to describe the social context and regulatory framework for
      third-party reproduction in Australia. This is a review of current laws and
      regulations related to third-party reproduction in Australia. Although subtle
      between-state differences exist, third-party reproduction is by and large a
      socially acceptable and legally permissible way to form a family throughout
      Australia. The overarching principles that govern the practice of third-party
      reproduction are altruism; the right of donorconceived people to be informed of
      their biological origins; and the provision of comprehensive counselling about
      the social, psychological, physical, ethical, financial and legal implications of
      third-party reproduction to those considering donating or receiving gametes or
      embryos and entering surrogacy arrangements. These principles ensure that donors
      are not motivated by financial gain, donor offspring can identify and meet with
      the person or persons who donated gametes or embryos, and prospective donors and
      recipients are aware of and have carefully considered the potential consequences
      of third-party reproduction. Australian state laws and federal guidelines
      prohibit commercial and anonymous third-party reproduction; mandate counselling
      of all parties involved in gamete and embryo donation and surrogacy arrangements;
      and require clinics to keep records with identifying and non- identifying
      information about the donor/s to allow donor-conceived offspring to trace their
      biological origins. 

PMID- 24851180
TI  - Molar pregnancy presents as tubal ectopic pregnancy.
AB  - Hydatidiform moles are abnormal gestations characterized by the presence of
      hydropic changes affecting some or all of the placental villi. Hydatidiform moles
      arise as a result of the fertilization of an abnormal ovum. In this report, the
      patient was a 29 year old Asian woman who had induction of ovulation with
      letrozol. Since the majority of molar gestations arise within the uterine cavity
      thus the occurrence of a hydatidiform mole within ectopic gestational tissue is
      rare. It is important to differentiate a hydatidiform mole from a conventional
      ectopic pregnancy, particularly in infertile women who have a history of
      ovulation induction. 

PMID- 24851182
TI  - Attributable healthcare utilization and cost of pneumonia due to drug-resistant
      streptococcus pneumonia: a cost analysis.
AB  - BACKGROUND: The burden of disease due to S. pneumoniae (pneumococcus),
      particularly pneumonia, remains high despite the widespread use of vaccines. Drug
      resistant strains complicate clinical treatment and may increase costs. We
      estimated the annual burden and incremental costs attributable to antibiotic
      resistance in pneumococcal pneumonia. METHODS: We derived estimates of healthcare
      utilization and cost (in 2012 dollars) attributable to penicillin, erythromycin
      and fluoroquinolone resistance by taking the estimate of disease burden from a
      previously described decision tree model of pneumococcal pneumonia in the U.S. We
      analyzed model outputs assuming only the existence of susceptible strains and
      calculating the resulting differences in cost and utilization. We modeled the
      cost of resistance from delayed resolution of illness and the resulting
      additional health services. RESULTS: Our model estimated that non-susceptibility
      to penicillin, erythromycin and fluoroquinolones directly caused 32,398
      additional outpatient visits and 19,336 hospitalizations for pneumococcal
      pneumonia. The incremental cost of antibiotic resistance was estimated to account
      for 4% ($91 million) of direct medical costs and 5% ($233 million) of total costs
      including work and productivity loss. Most of the incremental medical cost ($82
      million) was related to hospitalizations resulting from erythromycin non
      susceptibility. Among patients under age 18 years, erythromycin non
      susceptibility was estimated to cause 17% of hospitalizations for pneumonia and
      $38 million in costs, or 39% of pneumococcal pneumonia costs attributable to
      resistance. CONCLUSIONS: We estimate that antibiotic resistance in pneumococcal
      pneumonia leads to substantial healthcare utilization and cost, with more than
      one-third driven by macrolide resistance in children. With 5% of total
      pneumococcal costs directly attributable to resistance, strategies to reduce
      antibiotic resistance or improve antibiotic selection could lead to substantial
      savings.

PMID- 24851183
TI  - A 15-year-old adolescent with a rare pituitary lesion.
AB  - Cystic sellar lesions are a rare cause of hypopituitarism and extremely rare in
      the pediatric age group. The differential diagnosis is large and includes both
      primary pituitary abscesses and cystic components on pre-existing lesions, such
      as adenoma, craniopharyngioma, Rathke's cleft cyst, leukemia, granulomatous
      disease and lymphocytic hypophysitis. In the absence of a definitive diagnosis,
      treatment can be challenging. We report a case of a 15-year-old female, who
      presented with headaches, altered consciousness and diplopia after a molar
      extraction, for which she had received oral antibiotics. Broad-spectrum i.v.
      antibiotics were given for presumed meningitis. Blood cultures failed to identify
      pathogens. Cerebral magnetic resonance imaging showed a pituitary cystic lesion.
      Endocrine studies revealed abnormal pituitary function. In the absence of a
      therapeutic response, the patient underwent a transsphenoidal biopsy of the
      pituitary gland, which yielded a purulent liquid, but cultures were negative.
      Histopathology showed lymphocytic infiltrates but no neutrophils, compatible with
      an inflammation of autoimmune or infectious origin. High-dose glucocorticoid
      therapy was started and pursued, along with i.v. antibiotics, for 6 weeks,
      leading to clinical and radiological improvement but with persistence of
      endocrine deficits. In conclusion, this is a case of secondary panhypopituitarism
      due to a cystic pituitary lesion, with a differential diagnosis of lymphocytic
      hypophysitis vs abscess in a context of decapitated meningitis. Combination
      therapy with antibiotics and glucocorticoids is a legitimate approach in the face
      of diagnostic uncertainty, given the morbidity, and even mortality, associated
      with these lesions. LEARNING POINTS: It is not always easy to differentiate
      primary cystic sellar lesions (such as a primary infectious pituitary abscess)
      from cystic components on pre-existing lesions (such as adenoma,
      craniopharyngioma, Rathke's cleft cyst, leukemia or lymphocytic
      hypophysitis).Because of the absence of specific symptoms and of
      immunohistochemical and serum markers, response to glucocorticoids can be the
      only way to differentiate lymphocytic hypophysitis from pituitary lesions of
      another origin. In addition, microbiological cultures are negative in 50% of
      cases of primary infectious sellar abscesses, thus the response to antibiotic
      treatment is often the key element to this diagnosis.A short course of high-dose
      glucocorticoids combined with antibiotics is not harmful in cases where there is
      no diagnostic certainty as to the origin of a cystic sellar mass, given the
      morbidity and mortality associated with these lesions.This approach may also
      diminish inflammation of either infectious or autoimmune origin while ensuring
      that the most likely pathogens are being targeted.

PMID- 24851181
TI  - Parallel developmental genetic features underlie stickleback gill raker
      evolution.
AB  - BACKGROUND: Convergent evolution, the repeated evolution of similar phenotypes in
      independent lineages, provides natural replicates to study mechanisms of
      evolution. Cases of convergent evolution might have the same underlying
      developmental and genetic bases, implying that some evolutionary trajectories
      might be predictable. In a classic example of convergent evolution, most
      freshwater populations of threespine stickleback fish have independently evolved
      a reduction of gill raker number to adapt to novel diets. Gill rakers are a
      segmentally reiterated set of dermal bones important for fish feeding. A previous
      large quantitative trait locus (QTL) mapping study using a marine * freshwater F2
      cross identified QTL on chromosomes 4 and 20 with large effects on evolved gill
      raker reduction. RESULTS: By examining skeletal morphology in adult and
      developing sticklebacks, we find heritable marine/freshwater differences in gill
      raker number and spacing that are specified early in development. Using the
      expression of the Ectodysplasin receptor (Edar) gene as a marker of raker
      primordia, we find that the differences are present before the budding of gill
      rakers occurs, suggesting an early change to a lateral inhibition process
      controlling raker primordia spacing. Through linkage mapping in F2 fish from
      crosses with three independently derived freshwater populations, we find in all
      three crosses QTL overlapping both previously identified QTL on chromosomes 4 and
      20 that control raker number. These two QTL affect the early spacing of gill
      raker buds. CONCLUSIONS: Collectively, these data demonstrate that parallel
      developmental genetic features underlie the convergent evolution of gill raker
      reduction in freshwater sticklebacks, suggesting that even highly polygenic
      adaptive traits can have a predictable developmental genetic basis.

PMID- 24851184
TI  - Bilateral and bimodal benefit as a function of age for adults.
AB  - BACKGROUND: Both bilateral cochlear implants (CIs) and bimodal (electric plus
      contralateral acoustic) stimulation can provide better speech intelligibility
      than a single CI. In both cases patients need to combine information from two
      ears into a single percept. In this paper we ask whether the physiological and
      psychological processes associated with aging alter the ability of bilateral and
      bimodal CI patients to combine information across two ears in the service of
      speech understanding. MATERIALS: The subjects were 60 adult bilateral CI patients
      and 91 adult bimodal patients. The test battery was composed of monosyllabic
      words presented in quiet and the AzBio sentences presented in quiet, at +10 and
      at +5 dB signal-to-noise ratio (SNR). METHODS: The subjects were tested in
      standard audiometric sound booths. Speech and noise were always presented from a
      single speaker directly in front of the listener. RESULTS: Age and bilateral or
      bimodal benefit were not significantly correlated for any test measure.
      CONCLUSION: Other factors equal, both bilateral CIs and bimodal CIs can be
      recommended for elderly patients.

PMID- 24851185
TI  - Healthcare providers' knowledge of disordered sleep, sleep assessment tools, and
      nonpharmacological sleep interventions for persons living with dementia: a
      national survey.
AB  - A large proportion of persons with dementia will also experience disordered
      sleep. Disordered sleep in dementia is a common reason for institutionalization
      and affects cognition, fall risk, agitation, self-care ability, and overall
      health and quality of life. This report presents findings of a survey of
      healthcare providers' awareness of sleep issues, assessment practices, and
      nonpharmacological sleep interventions for persons with dementia. There were 1846
      participants, with the majority being from nursing and rehabilitation. One-third
      worked in long-term care settings and one-third in acute care. Few reported
      working in the community. Findings revealed that participants understated the
      incidence of sleep deficiencies in persons with dementia and generally lacked
      awareness of the relationship between disordered sleep and dementia. Their
      knowledge of sleep assessment tools was limited to caregiver reports, self
      reports, and sleep diaries, with few using standardized tools or other assessment
      methods. The relationship between disordered sleep and comorbid conditions was
      not well understood. The three most common nonpharmacological sleep interventions
      participants identified using were a regular bedtime routine, increased daytime
      activity, and restricted caffeine. Awareness of other evidence-based
      interventions was low. These findings will guide evidence-informed research to
      develop and test more targeted and contextualized sleep and dementia knowledge
      translation strategies. 

PMID- 24851187
TI  - Gunshot wound contamination with squirrel tissue: wound care considerations.
AB  - While report of animal bites contaminating wounds is reported commonly, direct
      wound contamination with squirrel flesh has never been reported in the
      literature. The patient suffered an accidental self-inflicted gunshot wound that
      drove squirrel flesh and buck shot deep within his right buttock. This case
      outlines his hospital course and wound treatment. The patient was treated with
      ten days of broad spectrum antibiotics, extensive debridement of the wound in the
      operating room, and further treatment of the wound with a vacuum dressing system.
      While squirrel tissue and buckshot had to be removed from the wound on day six of
      the hospital stay, the patient remained afebrile without signs or symptoms of
      systemic illness. 

PMID- 24851186
TI  - The Response of Gray Treefrogs to Anesthesia by Tricaine Methanesulfonate (TMS or
      MS-222).
AB  - The design of anesthetic protocols for frogs is commonly hindered by lack of
      information. Results from fishes and rodents do not always apply to frogs, and
      the literature in anurans is concentrated on a few species. We report on the
      response of treefrogs (Hyla chrysoscelis and H. versicolor) to tricaine
      methanesulfonate. Body mass did not differ significantly between the species or
      between sexes. In the first exposure of a frog to TMS, variation in induction
      time was best explained by species (H. chrysoscelis resisted longer) and body
      mass (larger animals resisted longer). Multiple exposures revealed a strong
      effect of individual variation on induction time and a significant increase of
      induction time with number of previous anesthesia events within the same day.
      Recovery time was mostly explained by individual variation, but it increased with
      total time in anesthetic and decreased with induction time. It also increased
      with number of days since the last series of anesthesias and decreased with
      number of previous uses of the anesthetic bath. This is one of the first studies
      of anesthesia in hylids and also one of the first assessments of the factors that
      influence the variability of the response to anesthesia within a species.

PMID- 24851188
TI  - Dyspnea, tachycardia, and new onset seizure as a presentation of wilms tumor: a
      case report.
AB  - Wilms tumor is found in 1 in 10,000 children and most commonly presents in
      asymptomatic toddlers whose care givers notice a nontender abdominal mass in the
      right upper quadrant. This case of Wilms tumor presented as a critically ill
      eleven-year old with significant tachypnea, dyspnea, vague abdominal pain,
      intermittent emesis, new onset seizure, metabolic acidosis, and hypoxemia. This
      is the first case in the literature of Wilms Tumor with cavoatrial involvement
      and seizure and pulmonary embolism resulting in aggressive resuscitation and
      treatment. Treatment included anticoagulation, chemotherapy, nephrectomy, and
      surgical resection of thrombi, followed by adjunctive chemotherapy with pulmonary
      radiation. 

PMID- 24851189
TI  - Facing the danger zone: the use of ultrasound to distinguish cellulitis from
      abscess in facial infections.
AB  - Physical exam alone is often insufficient to determine whether or not cellulitis
      is accompanied by an abscess. Bedside ultrasound can be a valuable tool in ruling
      out suspected abscess by allowing direct visualization of a fluid collection. The
      proximity of the infection to adjacent structures can also be determined, thus
      aiding clinical decision making. Patients with cellulitis near the eye and nose
      are of particular concern due to the adjacent facial structures and the anatomy
      of the venous drainage. Accurately determining the presence or absence of an
      associated abscess in these patients is a crucial step in treatment planning. The
      purpose of this report is to (1) emphasize the benefits of bedside ultrasound
      when used in conjunction with the physical exam to rule out abscess; (2)
      demonstrate the utility of bedside ultrasound in planning a treatment strategy
      for soft tissue infection; (3) depict an instance where ultrasound detected an
      abscess when computed tomography (CT) scan did not. 

PMID- 24851190
TI  - Entamoeba dispar: A Rare Case of Enteritis in a Patient Living in a Nonendemic
      Area.
AB  - Entamoeba dispar, a common noninvasive parasite, is indistinguishable in its
      cysts and trophozoite forms from Entamoeba histolytica, the cause of invasive
      amebiasis, by microscopy. To differentiate the two species seems to be a problem
      for laboratory diagnosis. Recent experimental studies showed that  E. dispar can
      be considered pathogenic too. We present a rare case of enteritis due to E.
      dispar. 

PMID- 24851191
TI  - SYK as a New Therapeutic Target in B-Cell Precursor Acute Lymphoblastic Leukemia.
AB  - The identification of SYK as a master regulator of apoptosis controlling the
      activation of the PI3-K/AKT, NFkappaB, and STAT3 pathways-three major anti
      apoptotic signaling pathways in B-lineage leukemia/lymphoma cells-prompts the
      hypothesis that rationally designed inhibitors targeting SYK may overcome the
      resistance of malignant B-lineage lymphoid cells to apoptosis and thereby provide
      the foundation for more effective multi-modality treatment regimens for poor
      prognosis B-precursor acute lymphoblastic leukemia (BPL). In recent preclinical
      proof-of-concept studies, a liposomal nanoparticle (LNP) formulation of a SYK
      substrate-binding site inhibitor, known as C61, has been developed as a
      nanomedicine candidate against poor prognosis and relapsed BPL. This nanoscale
      formulation of C61 exhibited a uniquely favorable pharmacokinetics and safety
      profile in mice, induced apoptosis in radiation-resistant primary leukemic cells
      taken directly from BPL patients as well as in vivo clonogenic BPL xenograft
      cells, destroyed the leukemic stem cell fraction of BPL blasts, and exhibited
      potent in vivo anti-leukemic activity in xenograft models of aggressive BPL.
      Further development of C61-LNP may provide the foundation for new and effective
      treatment strategies against therapy-refractory BPL.

PMID- 24851192
TI  - Metabolomic Identification in Cerebrospinal Fluid of the Effects of High Dietary
      Cholesterol in a Rabbit Model of Alzheimer's Disease.
AB  - BACKGROUND: Alzheimer's disease (AD) is the most common neurodegenerative
      disorder, manifesting clinical symptoms of cognitive impairment and dementia. The
      vast majority of cases are late onset AD (LOAD), which are genetically
      heterogeneous and occur sporadically. The neuropathological changes of LOAD can
      be reproduced by supplementing a rabbit's diet with 2% cholesterol for 12 weeks.
      METHODS: In the present study, a non-targeted Fourier transform ion cyclotron
      resonance mass spectrometry based metabolomics approach and multivariate
      statistics were used to survey the effect of cholesterol on cerebrospinal fluid
      metabolites over a 12 week time-course. RESULTS: Of the 6515 accurate masses
      detected in the rabbit CSF, 375 showed significant differences in intensity (p <
      0.05) between samples collected at different time points. Further analysis of top
      95 (p < 0.01) revealed four clusters of metabolites with different expression
      patterns throughout the course of the cholesterol treatment. The majority of
      effects were observed in 12 weeks of cholesterol treated samples, while certain
      masses showed transient changes at 8 weeks but returned back to near the levels
      of the controls at 12 weeks. The masses that started to change 8 weeks into the
      treatment may represent early metabolic changes linked to certain defects in the
      brain related to AD development. Putative metabolite identifications revealed
      certain phosphorylated glycerolipids and peptide fragments decreased after 8
      weeks of cholesterol treatment. CONCLUSION: This study showed that there are
      specific metabolic perturbations which occur in the CSF as a result of high
      cholesterol loading. Given the changes of short peptide fragments in particular,
      the effects are likely the consequence of brain degeneration caused by high
      cholesterol levels. Further investigations of these masses will lead to a greater
      understanding of the metabolic mechanisms associated with cholesterol-related AD
      development. Some of these masses may be used as candidates for the development
      of diagnostic, prognostic or theranostic markers.

PMID- 24851193
TI  - Diagnostic Utility of Gene Expression Profiles.
AB  - Two crucial problems arise from a microarray experiment in which the primary
      objective is to locate differentially expressed genes for the diagnosis of
      diseases such as cancer and Alzheimer's. The first problem is the detection of a
      subset of genes which provides an optimum discriminatory power between diseased
      and normal subjects, and the second problem is the statistical estimation of
      discriminatory power from the optimum subset of genes between two groups of
      subjects. We develop a new method to select an optimum subset of discriminatory
      genes by searching over possible linear combinations of gene expression profiles
      and locating the one which provides the maximum discriminatory power between two
      sources of RNA as measured by the area under the receiver operating
      characteristic (ROC) curve. We further provide an estimate to the optimum
      discriminatory power between the diseased and the healthy subjects over the
      selected subsets of genes. The proposed stepwise approach takes in account of the
      gene-to-gene correlations in the estimation of discriminating power as well as
      the associated variability and allows the number of genes to be selected based on
      the increment of the discriminating power. Finally, the proposed methodology is
      applied to a benchmark microarray experiment and compared to the results obtained
      through existing approaches in the literature.

PMID- 24851194
TI  - Diclazuril Protects against Maternal Gastrointestinal Syndrome and Congenital
      Toxoplasmosis.
AB  - BACKGROUND: Toxoplasmosis is a common cause of foodborne, gastrointestinal and
      congenital syndrome with particularly severe or unknown health consequences.
      There is no safe and effective preventive or therapeutic modality against
      congenital toxoplasmosis or to eliminate the persistent chronic infection.
      HYPOTHESIS: Diclazuril to be safe in pregnancy and effective against
      gastrointestinal toxoplasmosis. METHODS: CD1 programmed pregnant mice were
      divided into groups and administered a diet containing diclazuril, or sham
      control. Treatments were initiated on Day 5 of pregnancy and continued until Day
      16 when dams were euthanatized. On Day 8 of pregnancy dams were infected
      intraperitoneally with escalating doses of tachyzoites (0, 100, 300, 600) from
      Type II strain. Dams were monitored daily for distress, pain, and abortion and
      samples collected at the end of the experiments. RESULTS: Infected dams developed
      moderate to severe Toxoplasma related complications in tachyzoites dose dependent
      manner. Animals became anemic and showed hydrothorax, and ascities. Diclazuril
      effectively protected dams from ascities and anemia (p < 0.05). Infected dams
      showed splenomegaly, with massive infiltration of epithelioid cells compared with
      the protective effect of diclazuril in treated animals. Infected dams exhibited
      severe hepatitis (score 0 to 4 scale = 3.5 +/- 0.01) with influx of inflammatory
      and plasma cells, dysplastic hepatocytes, multinucleated giant cell
      transformation and hepatic cells necrosis. Diclazuril treatment significantly
      protected dams from hepatitis, also in tachyzoites dose (100, 300, 600) dependent
      manner (respectively infected-treated versus infected controls, p < 0.001, p <
      0.01 and p < 0.05). Colonic tissues were significantly shortened in length, with
      infiltration of lymphocytes, and macrophages and microabscess formations in the
      cryptic structures, with significant improvement in diclazuril treated animals.
      Additionally, the number of fetuses, fetal length and fetal weight were preserved
      in diclazuril treated dams. CONCLUSIONS: This is the first report describing of
      diclazuril safety in pregnancy as well as efficacy against mild to moderate
      hepato-gastrointestinal syndrome in dams and fetal toxoplasmosis (Special issue,
      "Treatment of Liver Diseases").

PMID- 24851195
TI  - Emerging Role of MicroRNA in Pancreatic Cancer.

PMID- 24851196
TI  - Considering Factors of and Knowledge About Patients in Handover Assessment.
AB  - The healthcare system is moving from one primary physician who assumes
      responsibility for each patient to a more team-based approach. Thus, assessing
      team communication is critical. This study characterizes and assesses the quality
      of hospitalist handover communications at shift change using the literature
      recommended content and language form elements. Quality handovers should contain
      the following content: patient identifiers, active issues, and care plans.
      Quality handovers also should include utterances in the following language forms:
      explanations, rationales, and directives. Interviews, observation, recording, and
      conversation analysis of hospitalist handover communications were used.
      Hospitalist handover utterances were assigned both content and language form
      codes. The proportion of quality element verbalization across all patient
      handovers was calculated. In addition, the impact of patient factors (new
      admission, new problem, acuity level) and handover receiver knowledge on the
      inclusion of quality elements was examined. The 106 individual patient handovers
      across 16 handover sessions were recorded. 39% contained all six quality
      elements. While the majority of handovers contained five out of six quality
      elements, only 48% included directives. There was also no difference in the
      inclusion of quality elements based on patient factors or handover receiver
      knowledge. Hospitalist handovers are lacking in directives. Efforts to improve
      handovers through enhanced electronic medical record systems and training may
      need to expand to hospitalists and other attending level physicians.

PMID- 24851197
TI  - Spatial Mutual Information as Similarity Measure for 3-D Brain Image
      Registration.
AB  - Information theoretic-based similarity measures, in particular mutual
      information, are widely used for intermodal/intersubject 3-D brain image
      registration. However, conventional mutual information does not consider spatial
      dependency between adjacent voxels in images, thus reducing its efficacy as a
      similarity measure in image registration. This paper first presents a review of
      the existing attempts to incorporate spatial dependency into the computation of
      mutual information (MI). Then, a recently introduced spatially dependent
      similarity measure, named spatial MI, is extended to 3-D brain image
      registration. This extension also eliminates its artifact for translational
      misregistration. Finally, the effectiveness of the proposed 3-D spatial MI as a
      similarity measure is compared with three existing MI measures by applying
      controlled levels of noise degradation to 3-D simulated brain images.

PMID- 24851198
TI  - The impact of sexual harassment on job satisfaction, turnover intentions, and
      absenteeism: findings from Pakistan compared to the United States.
AB  - The purpose of this study was to compare and contrast how differences in
      perceptions of sexual harassment impact productive work environments for
      employees in Pakistan as compared to the US; in particular, how it affects job
      satisfaction, turnover, and/or absenteeism. This study analyzed employee
      responses in Pakistan (n = 146) and the United States (n = 102, 76) using
      questionnaire data. Significant results indicated that employees who were
      sexually harassed reported (a) a decrease in job satisfaction (b) greater
      turnover intentions and (c) a higher rate of absenteeism. Cross-cultural
      comparisons indicated that (a) Pakistani employees who were sexually harassed had
      greater job dissatisfaction and higher overall absenteeism than did their US
      counterparts and (b) Pakistani women were more likely to use indirect strategies
      to manage sexual harassment than were US targets. 

PMID- 24851199
TI  - UV/Visible spectra of a series of natural and synthesised anthraquinones:
      experimental and quantum chemical approaches.
AB  - Root decoctions of anthraquinone-containing plants are often taken as postpartum
      tonic and aphrodisiac. Anthraquinones are known for their diverse biological
      activities, especially antioxidant and anticancer. A series of 35 anthraquinones
      was generated by isolation from Rubiaceae plants and synthesis. Their UV/vis
      spectrum depends on the nature and relative positions of auxochromic substituents
      on the basic skeleton. To predict the maximum absorption bands for the current
      series of anthraquinones, excited sate calculations were performed using TD-DFT,
      CIS, ZINDO methods. The results showed that the use of PBE0 or its combination
      with B3LYP and B3P86 hybrid functionals are the most suitable to reproduce
      accurately the experimental lambdaMAX. The structure-property relationships
      (SPRs) were established based on structural and electronic properties of the
      anthraquinones and showed (i) the importance of the number and position of OH
      groups and (ii) the positive contribution of the electrophilicity and hardness as
      electronic descriptors on position and amplitude of the maximum absorption bands.

PMID- 24851200
TI  - Fostering cultural inclusiveness and learning in culturally mixed business
      classes.
AB  - BACKGROUND: Business educators have advocated that in order to build faculty's
      intercultural capability, it is vital to provide them with professional
      development in using intercultural training resources and with "community of
      practice" support in adapting such resources for enhancing their students'
      intercultural learning. This approach has been adopted in an Australian action
      research project titled "Internationalisation at Home" (IaH), which involved
      providing faculty with professional development adapted from an established
      intercultural training resource - the EXCELL (Excellence in Cultural Experiential
      Learning and Leadership) Program. CASE DESCRIPTION: In this paper, we present two
      case studies of the implementation of the IaH Project in business schools at the
      University of Canberra and at Griffith University. Lessons learned from the first
      study were incorporated in the design and evaluation of the second one. Faculty
      leaders will describe how they engage and support colleagues in adapting
      components of EXCELL to foster cultural inclusiveness and facilitate students'
      intercultural competence development. As part of project evaluation, we
      hypothesised that students who participated in IaH courses would report greater
      levels of (1) cultural inclusiveness in their educational environment, and (2)
      cultural learning development, compared with students who were not enrolled in
      IaH courses. Research participants in the Canberra case study comprised an
      intervention group of 140 business undergraduates enrolled in an IaH course, and
      a control group of 59 non-IaH undergraduates. At Griffith, participants were 211
      first year management students in the intervention group and 84 students enrolled
      in a non-IaH first year course. DISCUSSION AND EVALUATION: In each case study, an
      end-of-semester survey showed that students who had completed courses with the
      IaH project intervention reported significantly greater levels of perceived
      cultural inclusiveness in multicultural classes, and of cultural learning
      development, than students in the control group. Faculty's reflections on project
      processes and outcomes further suggest that implementing strategic, structured
      active learning interventions such as in the IaH Project, could bring about more
      productive social interactions in multicultural classes and benefit domestic and
      especially international students. We will discuss implications of the findings
      for students' intercultural learning, faculty's needs for continual professional
      development, and the role of institutional support in intercultural competence
      development.

PMID- 24851201
TI  - Dose adjustment for normal eating: a role for the expert patient?
AB  - The Dose Adjustment for Normal Eating (DAFNE) programme of intensive insulin
      therapy for type 1 diabetes provides a structured educational intervention to
      improve glycemic control, reduce hypoglycemia and improve quality of life.
      Enhancement of self-management skills is a key element of DAFNE and patients
      acquire detailed skills in insulin dose adjustment. Following DAFNE training,
      patients report improved confidence in their ability to manage their own insulin
      dosing, but generally still seek and require the assistance of health
      professionals when making substantial changes to their insulin regimens. Some
      DAFNE trained patients may be able to assist their peers in aspects of diabetes
      management within a group environment, but widespread introduction of the expert
      patient/peer educator role in the self-management of type 1 diabetes, in
      particular related to insulin dose management, would require formal and detailed
      evaluation, preferably in randomized controlled clinical trials, before being
      introduced into routine clinical practice. 

PMID- 24851203
TI  - The role of heat shock response in insulin resistance and diabetes.
AB  - The expansion of life-style related diseases, such as metabolic syndrome (MS) and
      type 2 diabetes mellitus (T2DM), appears to be unstoppable. It is also difficult
      to cease their complications in spite of many antidiabetic medications or
      intervention of public administration. We and our collaborators found that
      physical medicine using simultaneous stimulation of heat with mild electric
      current activates heat shock response, thereby reducing visceral adiposity,
      insulin resistance, chronic inflammation and improving glucose homeostasis in
      mice models of T2DM, as well as in humans with MS or T2DM. This combination
      therapy exerts novel action on insulin signaling, beta-cell protection and body
      compositions, and may provide a new therapeutic alternative in diabetic treatment
      strategy. 

PMID- 24851202
TI  - Altered transendothelial transport of hormones as a contributor to diabetes.
AB  - The vascular endothelium is a dynamic structure responsible for the separation
      and regulated movement of biological material between circulation and
      interstitial fluid. Hormones and nutrients can move across the endothelium either
      via a transcellular or paracellular route. Transcellular endothelial transport is
      well understood and broadly acknowledged to play an important role in the normal
      and abnormal physiology of endothelial function. However, less is known about the
      role of the paracellular route. Although the concept of endothelial dysfunction
      in diabetes is now widely accepted, we suggest that alterations in paracellular
      transport should be studied in greater detail and incorporated into this model.
      In this review we provide an overview of endothelial paracellular permeability
      and discuss its potential importance in contributing to the development of
      diabetes and associated complications. Accordingly, we also contend that if
      better understood, altered endothelial paracellular permeability could be
      considered as a potential therapeutic target for diabetes. 

PMID- 24851204
TI  - Internet-based mentoring program for patients with type 1 diabetes.

PMID- 24851205
TI  - Prevalence and determinants of diabetic nephropathy in Korea: Korea national
      health and nutrition examination survey.
AB  - BACKGROUND: Diabetic nephropathy is a leading cause of end stage renal disease
      and is associated with an increased risk of cardiovascular mortality. It
      manifests as albuminuria or impaired glomerular filtration rate (GFR), and the
      prevalence of diabetic nephropathy varies with ethnicity. The prevalence of
      diabetic nephropathy and its determinants in Korean adults have not previously
      been studied at the national level. This cross-sectional study was undertaken to
      ascertain the prevalence and determinants of albuminuria and chronic kidney
      disease (CKD) in Korean patients with diabetes. METHODS: The Korea National
      Health and Nutrition Examination Survey (KNHANES) V, conducted in 2011, was used
      to define albuminuria (n=4,652), and the dataset of KNHANES IV-V (2008-2011) was
      used to define CKD (n=21,521). Selected samples were weighted to represent the
      entire civilian population in Korea. Albuminuria was defined as a spot urine
      albumin/creatinine ratio >30 mg/g. CKD was defined as a GFR <60 mL/min/1.73 m(2).
      RESULTS: Among subjects with diabetes, 26.7% had albuminuria, and 8.6% had CKD.
      Diabetes was associated with an approximate 2.5-fold increased risk of
      albuminuria, with virtually no difference between new-onset and previously
      diagnosed diabetes. Only systolic blood pressure was significantly associated
      with albuminuria, and old age, high serum triglyceride levels, and previous
      cardiovascular disease (CVD) were related with CKD in subjects with diabetes.
      CONCLUSION: Korean subjects with diabetes had a higher prevalence of albuminuria
      and CKD than those without diabetes. Blood pressure was associated with
      albuminuria, and age, triglyceride level, and previous CVD were independent
      determinants of CKD in subjects with diabetes.

PMID- 24851206
TI  - The appropriateness of the length of insulin needles based on determination of
      skin and subcutaneous fat thickness in the abdomen and upper arm in patients with
      type 2 diabetes.
AB  - BACKGROUND: Longer needle and complicated insulin injection technique such as
      injecting at a 45-degree angle and making skinfolds may decrease patient
      compliance to insulin injection therapy. In this light, shorter insulin needles
      have been recently developed. However, it is necessary to ascertain that such
      shorter needles are appropriate for Korean patients with diabetes as well.
      METHODS: First, the diverse demographic and diabetic features of 156 Korean
      adults with diabetes were collected by a questionnaire and a device unit of body
      fat measurement. The skin and subcutaneous fat thicknesses of each subject were
      measured by Ultrasound device with a 7- to 12-MHz probe. Data were analyzed using
      analysis of variance and multiple linear regression. RESULTS: The mean skin
      thickness was 2.29+/-0.37 mm in the abdomen and 2.00+/-0.34 mm in the upper arms,
      and the mean subcutaneous fat thickness was to 10.15+/-6.54 mm in the abdomen and
      5.50+/-2.68 mm in the upper arms. Our analysis showed that the factors affecting
      the skin thickness of the abdomen and upper arms were gender and body mass index
      (BMI), whereas the factors influencing the subcutaneous fat thickness in the
      abdomen were gender and BMI, and the factors influencing the subcutaneous fat
      thickness in the upper arms were gender, BMI, and age. Insulin fluids may not
      appear to be intradermally injected into the abdomen and upper arms at any needle
      lengths. The risk of intramuscular injection is likely to increase with longer
      insulin needles and lower BMI. CONCLUSION: It is recommended to fully inform the
      patients about the lengths of needles for insulin injections. As for the
      recommended needle length, the findings of this study indicate that needles as
      short as 4 mm are sufficient to deliver insulin for Korean patients with
      diabetes.

PMID- 24851207
TI  - A randomized controlled trial of an internet-based mentoring program for type 1
      diabetes patients with inadequate glycemic control.
AB  - BACKGROUND: To determine whether an internet-based mentoring program can improve
      glycemic control in subjects with type 1 diabetes mellitus (T1DM). METHODS:
      Subjects with T1DM on intensive insulin therapy and with hemoglobin A1c (HbA1c)
      >=8.0% were randomized to mentored (glucometer transmission with feedback from
      mentors) or control (glucometer transmission without feedback) groups and were
      examined for 12 weeks. Five mentors were interviewed and selected, of which two
      were T1DM patients themselves and three were parents with at least one child
      diagnosed with T1DM since more than 5 years ago. RESULTS: A total of 57 T1DM
      adult subjects with a mean duration after being diagnosed with diabetes of 7.4
      years were recruited from Samsung Medical Center. Unfortunately, the mentored
      group failed to show significant improvements in HbA1c levels or other outcomes,
      including the quality of life, after completion of the study. However, the
      mentored group monitored their blood glucose (1.41 vs. 0.30) and logged into our
      website (http://ubisens.co.kr/) more frequently (20.59 times vs. 5.07 times) than
      the control group. CONCLUSION: A 12-week internet-based mentoring program for
      T1DM patients with inadequate glycemic control did not prove to be superior to
      the usual follow-up. However, the noted increase in the subjects' frequency of
      blood glucose monitoring may lead to clinical benefits.

PMID- 24851208
TI  - Association of vaspin with metabolic syndrome: the pivotal role of insulin
      resistance.
AB  - BACKGROUND: Previous studies evaluating the relationship between serum vaspin
      concentrations and metabolic syndrome (MetS) have yielded contrasting results.
      Additionally, contribution of general and abdominal obesity, chronic
      inflammation, and insulin resistance to this relationship remains unknown.
      METHODS: In a cross-sectional setting, we investigated the association between
      vaspin and MetS in 145 subjects ranging from normoglycemia to type 2 diabetes.
      Vaspin concentrations were measured using enzyme-linked immunosorbent assay.
      RESULTS: Women had 29% higher vaspin concentrations compared with men. Subjects
      with MetS (51% of all participants) had higher vaspin concentrations (P=0.019 in
      women and P<0.001 in men). In logistic regression, vaspin significantly predicted
      raised fasting plasma glucose (P<0.001), and raised triglycerides (P<0.001) after
      controlling for age in both sexes. Moreover, vaspin was the significant predictor
      for reduced high-density lipoprotein cholesterol and raised waist circumference
      in women and men, respectively. Considering MetS as a whole, vaspin predicted
      MetS even after adjustment for age, medications, diabetes, total cholesterol, and
      waist circumference in both sexes (odds ratio [OR], 3.88; 95% confidence interval
      [CI], 1.36 to 11.05; P=0.011 for women; OR, 3.16; 95% CI, 1.28 to 7.78; P=0.012
      for men). However, this relationship rendered nonsignificant after introducing
      homeostasis model assessment of insulin resistance (HOMA-IR) in women (P=0.089)
      and high-sensitivity C-reactive protein (P=0.073) or HOMA-IR in men (P=0.095).
      CONCLUSION: Vaspin is associated with some but not all components of MetS. Vaspin
      is a predictor of MetS as a single entity, independent of obesity. This
      relationship is largely ascribed to the effects of insulin resistance and chronic
      inflammation.

PMID- 24851210
TI  - Letter: clinical marker of platelet hyperreactivity in diabetes mellitus
      (diabetes metab j 2013;37:423-8).

PMID- 24851209
TI  - Factors associated for mild cognitive impairment in older korean adults with type
      2 diabetes mellitus.
AB  - BACKGROUND: The aim of this study was to identify factors associated with mild
      cognitive impairment (MCI) in older Korean adults with type 2 diabetes mellitus.
      METHODS: A total of 226 older (age >=65 years) adults without a history of
      cerebrovascular disease or dementia participated in this study. Cognitive
      function was assessed with the Montreal Cognitive Assessment-Korean version (MoCA
      K). A MoCA-K score <23 was defined as MCI. RESULTS: The prevalence of MCI was
      32.7%. In a logistic regression analysis, age (>=74 years old vs. 65-68 years
      old; odds ratio [OR], 3.69; 95% confidence interval [CI], 1.55 to 8.82; P=0.003),
      educational background (college graduation vs. no school or elementary school
      graduation; OR, 0.16; 95% CI, 0.05 to 0.46; P=0.001), and systolic blood pressure
      (>=135 mm Hg vs. <=120 mm Hg; OR, 3.25; 95% CI, 1.29 to 8.17; P=0.012) were
      associated with MCI. CONCLUSION: More concentrated efforts focused on early
      detection and appropriate management of MCI may be required in older Korean
      adults with type 2 diabetes mellitus.

PMID- 24851211
TI  - Response: clinical marker of platelet hyperreactivity in diabetes mellitus
      (diabetes metab j 2013;37:423-8).

PMID- 24851212
TI  - Invasion and metastasis in the viewpoint of cell adhesive molecules.

PMID- 24851214
TI  - Preoperative body mass index and postoperative complications after pelvic
      exenteration in recurrent or locally advanced rectal cancer patients.

PMID- 24851213
TI  - The new stapler device is good, but needs more evaluation.

PMID- 24851215
TI  - Role of beta1-Integrin in Colorectal Cancer: Case-Control Study.
AB  - PURPOSE: In the metastatic process, interactions between circulating tumor cells
      (CTCs) and the extracellular matrix or surrounding cells are required. beta1
      Integrin may mediate these interactions. The aim of this study was to investigate
      whether beta1-integrin is associated with the detection of CTCs in colorectal
      cancer. METHODS: We enrolled 30 patients with colorectal cancer (experimental
      group) and 30 patients with benign diseases (control group). Blood samples were
      obtained from each group, carcinoembryonic antigen (CEA) mRNA for CTCs marker and
      beta1-integrin mRNA levels were estimated by using reverse transcription
      polymerase chain reaction, and the results were compared between the two groups.
      In the experimental group, preoperative results were compared with postoperative
      results for each marker. In addition, we analyzed the correlation between the
      expressions of beta1-integrin and CEA. RESULTS: CEA mRNA was detected more
      frequently in colorectal cancer patients than in control patients (P = 0.008).
      CEA mRNA was significantly reduced after surgery in the colorectal cancer
      patients (P = 0.032). beta1-Integrin mRNA was detected more in colorectal cancer
      patients than in the patients with benign diseases (P < 0.001). In colorectal
      cancer patients, expression of beta1-integrin mRNA was detected more for advanced
      stage cancer than for early-stage cancer (P = 0.033) and was significantly
      decreased after surgery (P < 0.001). In addition, expression of beta1-integrin
      mRNA was significantly associated with that of CEA mRNA in colorectal cancer
      patients (P = 0.001). CONCLUSION: In conclusion, beta1-integrin is a potential
      factor for forming a prognosis following surgical resection in colorectal cancer
      patients. beta1-Integrin may be a candidate for use as a marker for early
      detection of micrometastatic tumor cells and for monitoring the therapeutic
      response in colorectal cancer patients.

PMID- 24851216
TI  - Comparison of surgical skills in laparoscopic and robotic tasks between
      experienced surgeons and novices in laparoscopic surgery: an experimental study.
AB  - PURPOSE: Robotic surgery is known to provide an improved technical ability as
      compared to laparoscopic surgery. We aimed to compare the efficiency of surgical
      skills by performing the same experimental tasks using both laparoscopic and
      robotic systems in an attempt to determine if a robotic system has an advantage
      over laparoscopic system. METHODS: Twenty participants without any robotic
      experience, 10 laparoscopic novices (LN: medical students) and 10
      laparoscopically-experienced surgeons (LE: surgical trainees and fellows),
      performed 3 laparoscopic and robotic training-box-based tasks. This entire set of
      tasks was performed twice. RESULTS: Compared with LN, LEs showed significantly
      better performances in all laparoscopic tasks and in robotic task 3 during the 2
      trials. Within the LN group, better performances were shown in all robotic tasks
      compared with the same laparoscopic tasks. However, in the LE group, compared
      with the same laparoscopic tasks, significantly better performance was seen only
      in robotic task 1. When we compared the 2 sets of trials, in the second trial, LN
      showed better performances in laparoscopic task 2 and robotic task 3; LE showed
      significantly better performance only in robotic task 3. CONCLUSION: Robotic
      surgery had better performance than laparoscopic surgery in all tasks during the
      two trials. However, these results were more noticeable for LN. These results
      suggest that robotic surgery can be easily learned without laparoscopic
      experience because of its technical advantages. However, further experimental
      trials are needed to investigate the advantages of robotic surgery in more
      detail.

PMID- 24851217
TI  - Niti CAR 27 Versus a Conventional End-to-End Anastomosis Stapler in a
      Laparoscopic Anterior Resection for Sigmoid Colon Cancer.
AB  - PURPOSE: The Niti CAR 27 (ColonRing) uses compression to create an anastomosis.
      This study aimed to investigate the safety and the effectiveness of the
      anastomosis created with the Niti CAR 27 in a laparoscopic anterior resection for
      sigmoid colon cancer. METHODS: In a single-center study, 157 consecutive patients
      who received an operation between March 2010 and December 2011 were
      retrospectively assessed. The Niti CAR 27 (CAR group, 63 patients) colorectal
      anastomoses were compared with the conventional double-stapled (CDS group, 94
      patients) colorectal anastomoses. Intraoperative, immediate postoperative and 6
      month follow-up data were recorded. RESULTS: There were no statistically
      significant differences between the two groups in terms of age, gender, tumor
      location and other clinical characteristics. One patient (1.6%) in the CAR group
      and 2 patients (2.1%) in the CDS group experienced complications of anastomotic
      leakage (P = 0.647). These three patients underwent a diverting loop ileostomy.
      There were 2 cases (2.1%) of bleeding at the anastomosis site in the CDS group.
      All patients underwent a follow-up colonoscopy (median, 6 months). One patient in
      the CAR group experienced anastomotic stricture (1.6% vs. 0%; P = 0.401). This
      complication was solved by using balloon dilatation. CONCLUSION: Anastomosis
      using the Niti CAR 27 device in a laparoscopic anterior resection for sigmoid
      colon cancer is safe and feasible. Its use is equivalent to that of the
      conventional double-stapler.

PMID- 24851218
TI  - Preoperative body mass index, 30-day postoperative morbidity, length of stay and
      quality of life in patients undergoing pelvic exenteration surgery for recurrent
      and locally-advanced rectal cancer.
AB  - PURPOSE: Malnutrition is associated with an increased risk of developing
      complications following gastrointestinal surgery, especially following radical
      surgeries such as pelvic exenteration. This study aims to determine if
      preoperative body mass index (BMI) is associated with 30-day morbidity, length of
      hospital stay and/or quality of life (QoL) in patients undergoing pelvic
      exenteration surgery for recurrent and locally-advanced rectal cancer prior to a
      prospective trial. METHODS: A review of all patients who underwent pelvic
      exenteration surgery prior to 2008 was performed. Patients were included if they
      had a documented BMI as well as a QoL measurement (Functional Assessment Cancer
      Therapy - Colorectal questionnaire). RESULTS: Thirty-one patients, with a mean
      age of 56 years, had preoperative height and weight data, as well as measures of
      postoperative QoL, and formed the study group. The numbers of patients with
      recurrent (n = 17) or locally-advanced rectal cancer (n = 14) were similar. The
      mean length of stay was 21 days while the mean BMI of the patients was 24.3 (+/-
      5.9) kg/m(2). The majority of the patients were either of normal weight (n = 15)
      or overweight/obese (n = 11). The average length of hospital stay was
      significantly longer in patients who were underweight compared to those who were
      of normal weight (F = 6.508, P = 0.006) and those who were overweight and obese
      (F = 6.508, P = 0.007). CONCLUSION: This study suggests that a lower body mass
      index preoperatively is associated with a longer length of hospital stay. BMI is
      not associated with long-term QoL in this patient group. However, further
      prospective research is required.

PMID- 24851220
TI  - An extragastrointestinal stromal tumor in the omentum with peritoneal seeding
      mimicking an appendiceal mucinous cancer with carcinomatosis.
AB  - Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of
      the gastrointestinal tract. These tumors tend to present most frequently in the
      stomach, followed by the small intestine. GISTs can also arise from the omentum,
      retroperitoneum, mesentery, or pleura and are termed extragastrointestinal
      stromal tumors (EGISTs) when they do so. EGISTs arising from the omentum are very
      rare. Due to the limited incidence of EGISTs in the omentum, the diagnostic
      criteria are not well established, and making a correct diagnosis may be
      difficult. In this report, we present a case of an EGIST of the omentum with
      peritoneal metastasis that was initially suspected to be an appendiceal mucinous
      carcinoma with carcinomatosis on positron emission tomography/computed tomography
      imaging. 

PMID- 24851219
TI  - A survey of colonoscopic surveillance after polypectomy.
AB  - PURPOSE: Several guidelines have been proposed for surveillance colonoscopy after
      polypectomy. However, some discrepancies still exist between the guidelines and
      clinical practice. This study was conducted to identify Korean doctors'
      recommendations for the colonoscopic surveillance interval after polypectomy.
      METHODS: A survey of the attendees at the symposium of the 64th Annual Congress
      of the Korean Surgical Society was conducted. When the prepared clinical
      scenarios were given, attendees answered using a wireless radio-frequency
      audience response system. All responders' results were automatically counted
      immediately. Frequencies of different answers to each question were calculated,
      and our results were compared with those of previous surveys performed using the
      same questionnaire in the United States or Japan. RESULTS: The number of
      responder varied from 38 to 41. About 50% of valid responders selected 'follow-up
      in 3 years' for low-risk lesions, such as a 6-mm hyperplastic polyp, a 6-mm
      tubular adenoma, or two 6-mm tubular adenomas. Responders most-commonly selected
      'follow-up in 1 year' for high-risk lesions, such as a 12-mm tubular adenoma with
      high grade dysplasia or a 12-mm tubulovillous adenoma. The majority of Korean
      doctors recommend postpolypectomy colonoscopic surveillance more frequently than
      American physicians did. CONCLUSION: A discrepancy between the guidelines and
      clinical practice for the surveillance after polypectomy still exists in Korea. A
      surveillance program that can be easily and widely applied in clinical practice
      needs to be established.

PMID- 24851221
TI  - Surgical Management of Unicentric Castleman's Disease in the Abdomen.
AB  - Castleman's disease (CD) is a rare lymphoproliferative disorder that can involve
      single or multiple lymph nodes in the body. Especially, the localized form of CD
      is known to be well-controlled by using a surgical resection. On occasion, the
      surgeon may confront an abdominal and retroperitoneal mass of unknown origin.
      Thus, we present this case in which we treated a 16-year-old female patient for
      CD and investigated how to evaluate and manage the situation from the standpoint
      of CD. Also, we give a review of the pathology, clinical manifestation,
      diagnosis, and treatment of CD. 

PMID- 24851222
TI  - Cervical bronchogenic cysts mimic metastatic lymph nodes during thyroid cancer
      surgery.
AB  - PURPOSE: Although congenital bronchogenic cysts in the cervical region,
      especially in the thyroid or perithyroidal area, are rare, distinguishing them
      from other cervical cystic lesions (e.g., thyroglossal duct and branchial cleft
      cysts) and metastatic cervical lymph nodes is difficult preoperatively.
      Additionally, cystic degeneration of metastatic lymph nodes is common in patients
      with thyroid cancer. We investigated the clinical characteristics and proper
      treatment for individuals with cervical bronchogenic cysts. METHODS: Of the
      18,900 patients treated for thyroid cancer, 18 patients with pathologically
      confirmed bronchogenic cysts were retrospectively reviewed. Bilateral total
      thyroidectomy or less than total thyroidectomy with central compartment node
      dissection, including cystic mass excision was done and cystic mass was confirmed
      by postoperative pathologic examination. RESULTS: All cervical bronchogenic cysts
      were asymptomatic. Their mean size was 1.2 cm (range, 0.3 to 3 cm). Of these 18
      patients, 15 did not have any abnormal radiological findings, except for
      lymphadenopathy during preoperative evaluations. Most bronchogenic cysts were
      detected around the thyroid and paratracheal areas. On preoperative imaging and
      intraoperatively, most were indistinguishable from metastatic cervical lymph
      nodes or other cystic lesions. CONCLUSION: Although cervical bronchogenic cysts
      are rare and benign, they should be distinguished from other cystic cervical
      masses, especially metastatic cervical lymph nodes associated with thyroid
      cancer. Possible cervical bronchogenic cysts found during thyroid cancer
      evaluation or surgery should be surgically excised.

PMID- 24851223
TI  - Laparoscopic treatment of hepatic cysts located in the posterosuperior segments
      of the liver.
AB  - PURPOSE: Laparoscopy is considered the treatment of choice for hepatic cysts,
      especially those located in anterolateral segments (AL; segments II, III, IVb, V,
      and VI) because of the ease of laparoscopic access. Here, we evaluated the
      feasibility and safety of laparoscopic treatment of hepatic cysts in
      posterosuperior segments (PS; segments I, IVa, VII, and VIII). METHODS: We
      retrospectively analyzed clinical data for 34 patients who underwent laparoscopic
      treatment of hepatic cysts between September 2004 and December 2012. Patients
      were divided into two groups depending on whether the main largest cyst was
      located in AL (n = 20) or PS (n = 14). Laparoscopic cyst unroofing was performed
      in 29 patients with symptomatic simple cysts. Laparoscopic resection was
      performed in 5 patients with suspected cystic neoplasms. RESULTS: There were no
      deaths or major complications. The mean operation time was 110 minutes and the
      mean hospital stay was 4.4 days. The mean cyst size was not significantly
      different (P = 0.511) but the frequency of multiple cysts was significantly
      greater in group PS (P = 0.003). The predominant type of resection was unroofing
      in both groups (P = 0.251). The mean blood loss (P = 0.747), mean hospital stay
      (P = 0.812), mean operation time (P = 0.669), morbidity rate (P = 0.488), and
      relapse rate (P = 0.448) were not significantly different. Relapse occurred in
      one patient who underwent reunroofing 17 months later. The median follow-up is 62
      months. CONCLUSION: Laparoscopy is a safe procedure for hepatic cysts located in
      posterosuperior segments.

PMID- 24851224
TI  - Comprehension of readmission after laparoscopy assisted distal gastrectomy: what
      are the causes?
AB  - PURPOSE: The aim of this study is to evaluate long-term outcomes regarding
      readmission for laparoscopy-assisted distal subtotal gastrectomy (LADG) compared
      to conventional open distal subtotal gastrectomy (CODG) for early gastric cancer
      (EGC). METHODS: Between January 2003 and December 2006, 223 and 106 patients
      underwent LADG and CODG, respectively, for EGC by one surgeon. The
      clinicopathologic characteristics, postoperative outcomes, postoperative
      complications, overall 5-year survival, recurrence, and readmission were
      retrospectively compared between the two groups. RESULTS: Multiple readmission
      rate in LADG was significantly less than that in CODG (0.4% vs. 3.8%, P = 0.039),
      although the readmission rate, reoperation rate after discharge, and mean
      readmission days were not significantly different between the two groups.
      Readmission rates of the LADG and CODG groups were 12.6% and 14.2%, respectively.
      First flatus time and postoperative hospital stay was significantly shorter in
      the LADG group. However, there was no significant difference in the complication
      rates between the two groups. Overall 5-year survival rates of the LADG and CODG
      group were 100% and 99.1% (P = 0.038), respectively. CONCLUSION: Compared to the
      CODG group, the LADG group has several advantages in surgical short-term outcome
      and some benefit in terms of readmission in surgical long-term outcome for
      patients with EGC, even though the oncologic outcome of LADG is similar to that
      of CODG over 5 years.

PMID- 24851225
TI  - Adult intussusceptions: preoperative predictive factors for malignant lead point.
AB  - PURPOSE: Adult intussusception is uncommon, but an organic lesion is found to be
      the lead point in 75% to 90% of the cases. This study was designed to review our
      experience with adult intussusception and to determine if there are any
      preoperative predictive factors for a malignant lead point. METHODS: Thirty-three
      patients over 15 years of age were diagnosed with intussusceptions through
      operative finding over a period of 20 years. We reviewed the medical records of
      these patients retrospectively, and preoperative predictive factors of malignant
      lead points were analyzed. RESULTS: The preoperative diagnosis of intussusception
      had been made correctly in 86% of the cases, and computed tomography could find a
      lead point in 79%. A causative organic lesion was found in 29 patients (88%)
      pathologically; 16 cases (48%) were due to benign tumors, and 13 (39%) were due
      to malignant tumors. A malignant lead point was present in four of 21 enteric
      (20%) versus nine of 13 colonic intussusceptions (75%). The period from symptom
      appearance to hospital visit showed a more chronic nature in malignant neoplasm
      than in benign neoplasm (P = 0.006), and the location of causative organic lesion
      showed significant difference between benign and malignant groups (P = 0.003).
      CONCLUSION: Adult intussusceptions are commonly secondary to a pathologic lead
      point, and a computed tomography is an effective diagnostic tool for finding a
      lead point preoperatively. The chronic nature of the disease presentation and
      colonic location of the lead point may suggest a malignant neoplasm.

PMID- 24851226
TI  - Comparison of abdominal and perineal procedures for complete rectal prolapse: an
      analysis of 104 patients.
AB  - PURPOSE: Selecting the best surgical approach for treating complete rectal
      prolapse involves comparing the operative and functional outcomes of the
      procedures. The aims of this study were to evaluate and compare the operative and
      functional outcomes of abdominal and perineal surgical procedures for patients
      with complete rectal prolapse. METHODS: A retrospective study of patients with
      complete rectal prolapse who had operations at a tertiary referral hospital and a
      university hospital between March 1990 and May 2011 was conducted. Patients were
      classified according to the type of operation: abdominal procedure (AP) (n = 64)
      or perineal procedure (PP) (n = 40). The operative outcomes and functional
      results were assessed. RESULTS: The AP group had the younger and more men than
      the PP group. The AP group had longer operation times than the PP group (165
      minutes vs. 70 minutes; P = 0.001) and longer hospital stays (10 days vs. 7 days;
      P = 0.001), but a lower overall recurrence rate (6.3% vs. 15.0%; P = 0.14). The
      overall rate of the major complication was similar in the both groups (10.9% vs.
      6.8%; P = 0.47). The patients in the AP group complained more frequently of
      constipation than of incontinence, conversely, in the PP group of incontinence
      than of constipation. CONCLUSION: The two approaches for treating complete rectal
      prolapse did not differ with regard to postoperative morbidity, but the overall
      recurrence tended to occur frequently among patients in the PP group. Functional
      results after each surgical approach need to be considered for the selection of
      procedure.

PMID- 24851227
TI  - High pretransplant HBV level predicts HBV reactivation after kidney
      transplantation in HBV infected recipients.
AB  - PURPOSE: HBsAg-positive kidney recipients are at increased risk for mortality and
      graft failure. The aims of this study were to identify the outcomes of HBsAg
      positive recipients who received preemptive antiviral agents after successful
      kidney transplantation and to analyze risk factors for HBV reactivation. METHODS:
      We retrospectively reviewed the medical records of 944 patients performed kidney
      transplantation between 1999 and 2010. RESULTS: HBsAg-negative recipients were
      902 patients and HBsAg-positive recipients, 42. Among HBsAg-positive recipients,
      HBV reactivation was detected in 7 patients and well controlled by switch or
      combination therapy. Graft failure developed in only one patient due to chronic
      rejection regardless of HBV reactivation but no deaths occurred. All patients
      were alive at the end of follow-up and none developed end-stage liver disease or
      hepatocellular carcinoma. There was statistically significant difference in graft
      survival between HBsAg-positive recipients and HBsAg-negative. Multivariate
      analysis identified increased HBV DNA levels (>5 * 10(4) IU/mL) in the HBsAg
      positive kidney transplant recipients as a risk factor for HBV reactivation (P =
      0.007). CONCLUSION: Effective viral suppression with antiviral agents in HBsAg
      positive renal transplant recipients improves patient outcome and allograft
      survival. Antiviral therapy may be especially beneficial in patients with high
      HBV DNA levels prior to transplantation.

PMID- 24851228
TI  - Hiatal hernia in pediatric patients: laparoscopic versus open approaches.
AB  - PURPOSE: The aim of this study was to evaluate the surgical outcomes of
      laparoscopic approach for hiatal hernia (HH) in pediatric patients. METHODS: This
      was a retrospective study of 33 patients younger than 18 years who underwent an
      operation for HH between January 1999 and December 2012. RESULTS: The HH symptoms
      were various and included regurgitation, vomiting, weight loss, cough,
      hoarseness, and cyanosis. Among the 33 patients, there were 25 sliding types, 1
      paraesophageal type, and 7 mixed types. Open surgery (OS) and laparoscopic
      surgery (LS) were used in 16 and 17 patients, respectively. There were no
      statistically significant differences in sex, age, or body weight between the
      groups. The median operating time was longer in the LS group (150 minutes; range,
      90-250 minutes vs. 125 minutes; range, 66-194 minutes; P = 0.028). Time to oral
      intake was shorter in the LS group than in the OS group (1 day; range, 1-3 days
      vs. 2 days; range, 1-7 days; P = 0.001) and time to full feeding was shorter in
      the LS group than in the OS group (6 days; range, 3-16 days vs. 10 days; range, 3
      33 days; P = 0.048). There were no differences in length of hospital stay and
      complications between the two groups. There was no perioperative mortality or
      recurrence of HH. CONCLUSION: A good surgical outcome for laparoscopic correction
      of HH was seen in pediatric patients.

PMID- 24851229
TI  - Chronic gastric anisakiasis provoking a bleeding gastric ulcer.
AB  - Gastric anisakiasis is a parasitic disease caused by the gastric mucosal
      penetration of the Anisakis larvae ingested with raw fish. Acute gastric
      anisakiasis is diagnosed by the endoscopic visualization of Anisakis larvae along
      with mucosal edema, erythema, hemorrhage, and/or an ulcer, whereas chronic
      anisakiasis is often observed as a localized tumor commonly occurring in the
      submucosal layer, and is characterized by eosinophilic granuloma with edema and
      embedded Anisakis larvae on pathological examination of surgical specimens. We
      report here a case of chronic gastric anisakiasis provoking a bleeding gastric
      ulcer, which is a rare clinical manifestation of this condition. 

PMID- 24851230
TI  - Repair of type I endoleak by chimney technique after endovascular abdominal
      aortic aneurysm repair.
AB  - Endovascular aneurysm repair is a minimally invasive, durable and effective
      alternative to open surgery for treatment of abdominal aortic aneurysms (AAA).
      However, in patients who do not have an adequate sealing zone, open surgical
      repair is required, which may increase mortality and morbidity. An alternative
      treatment in patients with challenging anatomy is the so-called "chimney graft"
      technique. Here, we describe a case using the chimney graft technique for
      treatment of juxtarenal type I endoleak followed by a previous conventional stent
      graft insertion to the AAA with good results. 

PMID- 24851231
TI  - The experience of transumbilical endoscopic appendectomies.
AB  - Minimally invasive surgery is being widely accepted in various fields of surgery.
      Although several appendectomy techniques have been reported but, there is no
      standardization. We report here the experiences of transumbilical endoscopic
      appendectomy in humans. Between July 2008 and September 2010, ten patients with
      appendicitis successfully underwent transumbilical endoscopic appendectomies.
      There were 7 cases of suppurative, 2 cases of gangrenous and 1 case of perforated
      in operative findings. The ages of the patients were 13-56 years (mean age, 32.7
      +/- 15.4 years). Under general anesthesia, a 15-mm port was inserted through the
      umbilicus and then a two-channel endoscope was inserted in the peritoneal cavity.
      After appendix identification, counter-traction of the appendix with a direct
      abdominal wall puncture using a straight round needle prolene was performed to
      achieve good visualization of the operative field. Tissue dissection was
      performed using an endoscopic needle knife. Tissue grasping and resected appendix
      retrieval were done with endoscopic forceps. The average operation time was 79.5
      +/- 23.6 minutes (range, 45 to 110 minutes). No procedures were converted to
      laparoscopic or open appendectomy. Hospital stay was 4-6 days. All patients
      completely recovered without complications. As it is highly maneuverable, we
      believe transumbilical endoscopic appendectomy can be a feasible method. And, as
      surgeons want to proceed from laparoscopic surgery to natural orifice
      transluminal endoscopic surgery, this procedure could be a triable method. 

PMID- 24851232
TI  - Associations between cognitive, sociocontextual, and affective variables and
      unprotected anal intercourse among men who have sex with men--a comparative study
      conducted in two Chinese cities.
AB  - Few studies compared HIV-related risk behaviors between cities with different
      sociocultural environments among men who have sex with men (MSM). This study
      investigated the prevalence of unprotected anal intercourse (UAI) and associated
      individual and socio-cultural factors among Chinese MSM in Hong Kong and Shenzhen
      in Mainland China, which were proximal to each other but experienced different
      socioeconomic developments. Amongst all the 535 participants, 40.2% had had UAI.
      Significant factors of UAI among Shenzhen MSM included being able to find someone
      to share one's sexual orientation, disclosure of sexual orientation to family
      members, HIV risk perception, and use of alcohol or substances (adjusted OR
      ranged from 2.37 to 4.91), whilst disclosure of sexual orientation to family
      members was the only significant factor among Hong Kong MSM (adjusted OR = 1.64).
      Geographic variations in factors associated with UAI were observed. Future
      research and interventions need to take this into account. 

PMID- 24851233
TI  - Cardiovascular MRI in Detection and Measurement of Aortic Atheroma in Stroke/TIA
      patients.
AB  - BACKGROUND: Aortic Atheroma (AoA) is an independent risk factor for new and
      recurrent stroke. AoA ulceration and mobility are associated with an increased
      risk for brain embolism. Transesophageal echocardiography (TEE) is the gold
      standard for detection and measurement of AoA in stroke/TIA patients.
      Cardiovascular MRI (cMRI) could be an alternative, non-invasive imaging modality
      for stroke/TIA patients. The objective of this study was to assess the accuracy
      and correlation of AoA detected and measured by cMRI versus TEE in patients with
      recent stroke/TIA. METHODS AND RESULTS: Twenty-two stroke/TIA patients undergoing
      TEE as a part of their stroke workup consented to a protocol-mandated cMRI
      performed on a 1.5 T magnet. The protocol included an axial non-breathhold EKG
      gated dual-echo spin echo MRI of the thoracic aorta (TR/TE1/TE2=900/29/69) and a
      contrast-enhanced breathhold 3D gradient-echo image of the thorax
      (flip/TR/TE=12/4.0/1.71). Maximum plaque thickness, ulceration (>= 2 mm) and
      mobility of AoA were assessed in the proximal (ascending and proximal arch) and
      distal (distal arch and descending) segments of thoracic aorta by a cardiologist
      to interpret the TEE and a radiologist to interpret the cMRI. There was good
      correlation between cMRI and TEE in measurement of plaque thickness in the
      proximal segments (R=0.73, p<0.0001) and the distal segments (R=0.81, p<0.0001)
      of the aortic arch (AA). cMRI had a high degree of accuracy in detecting
      measurable AoA (>= 1 mm) in the proximal segments (sensitivity 90%, specificity
      100%), as well as the distal segments (sensitivity 67%, specificity 100%). cMRI
      also had a high degree of accuracy in detecting significant AoA (>= 4 mm) in
      proximal segments (sensitivity 71%, specificity 93%), as well as distal segments
      (sensitivity 71%, specificity 100%). CONCLUSION: The study showed a high degree
      of accuracy and correlation of AoA detected and measured by cMRI as compared to
      TEE in patients with recent stroke/TIA. This technique has limitations in
      detection of AoA ulceration, and protocols assessing AoA mobility need to be
      developed.

PMID- 24851234
TI  - CT Angiography and Presentation NIH stroke Scale in Predicting TIA in Patients
      Presenting with Acute Stroke Symptoms.
AB  - Patient candidacy for acute stroke intervention, is currently assessed using
      brain computed tomography angiography (CTA) evidence of significant
      stenosis/occlusion (SSO) with a high National Institutes of Health Stroke Scale
      (NIHSS) (>6). This study examined the association between CTA without significant
      stenosis/occlusion (NSSO) and lower NIHSS (<= 6) with transient ischemic attack
      (TIA) and other good clinical outcomes at discharge. Patients presenting <8 hours
      from stroke symptom onset, had an NIHSS assessment and brain CTA performed at
      presentation. Good clinical outcomes were defined as: discharge diagnosis of TIA,
      modified Rankin Score [mRS] <= 1, and home as the discharge disposition. Eighty
      five patients received both an NIHSS at presentation and a CTA at 4.2 +/- 2.2
      hours from stroke symptom onset. Patients with NSSO on CTA as well as those with
      NIHSS<=6 had better outcomes at discharge (p<0.001). NIHSS <= 6 were more likely
      than NSSO (p=0.01) to have a discharge diagnosis of TIA (p<0.001). NSSO on CTA
      and NIHSS <= 6 also correlated with fewer deaths (p<0.001). Multivariable
      analyses showed NSSO on CTA (Adjusted OR: 5.8 95% CI: 1.2-27.0, p=0.03)
      independently predicted the discharge diagnosis of TIA. Addition of NIHSS <= 6 to
      NSSO on CTA proved to be a stronger independent predictor of TIA (Adjusted OR
      18.7 95% CI: 3.5-98.9, p=0.001).

PMID- 24851235
TI  - Type 1 fimbriae in commensal Escherichia coli derived from healthy humans.
AB  - Type 1 fimbriae are one of the most important factors of Escherichia coli
      adaptation to different niches in the host. Our study indicated that the genetic
      marker--fimH gene occurred commonly in commensal E. coli derived from healthy
      humans but expression of the type 1 fimbriae was not observed. Identification of
      fim structural subunit genes (fimA-fimH) and recombinase fimE and fimB genes
      showed that many of the strains were carrying an incomplete set of genes and the
      genes expression study revealed that in strains with complete set of fim genes,
      the fimC gene, encoding the chaperone protein, was not expressed.

PMID- 24851237
TI  - Blockade of glutamate release by botulinum neurotoxin type A in humans: a dermal
      microdialysis study.
AB  - BACKGROUND: The analgesic action of botulinum neurotoxin type A (BoNTA) has been
      linked to the blockade of peripheral release of neuropeptides and
      neurotransmitters in animal models; however, there is no direct evidence of this
      in humans. OBJECTIVES: To investigate the effect of BoNTA on glutamate release in
      humans, using an experimental model of pain and sensitization provoked by
      capsaicin plus mild heat. METHODS: Twelve healthy volunteers (six men, six women)
      were pretreated with BoNTA (10 U) on the volar forearm and with a saline control
      on the contralateral side. Dermal microdialysis was applied one week later to
      collect interstitial samples before and after the application of a capsaicin
      patch (8%) plus mild heat (40 degrees C/60 min) to provoke glutamate release,
      pain and vasodilation. Samples were collected every hour for 3 h using linear
      microdialysis probes (10 mm, 100 kD). Dialysate was analyzed for glutamate
      concentration. Pain intensity and skin vasomotor reactions (temperature and blood
      flow changes) were also recorded. RESULTS: BoNTA significantly reduced glutamate
      release compared with saline (P<0.05). The provoked pain intensity was lower in
      the BoNTA-pretreated arm (P<0.01). The reduction in pain scores was not
      correlated with glutamate level. Cutaneous blood flow (P<0.05), but not cutaneous
      temperature (P>=0.05), was significantly reduced by BoNTA. There was a
      correlation between glutamate level and skin blood flow (r=0.58/P<0.05) but not
      skin temperature (P>=0.05). No differences according to sex were observed in any
      response. CONCLUSIONS: The present study provided the first direct evidence
      supporting the inhibitory effect of BoNTA on glutamate release in human skin,
      which is potentially responsible for some of the analgesic action of BoNTA.

PMID- 24851238
TI  - Adherence of pain assessment to the German national standard for pain management
      in 12 nursing homes.
AB  - BACKGROUND: Pain is very common among nursing home residents. The assessment of
      pain is a prerequisite for effective multiprofessional pain management. Within
      the framework of the German health services research project, 'Action Alliance
      Pain-Free City Muenster', the authors investigated pain assessment adherence
      according to the German national Expert Standard for Pain Management in Nursing,
      which is a general standard applicable to all chronic/acute pain-affected persons
      and highly recommended for practice. OBJECTIVES: To evaluate the state of pain
      assessment and to identify need for improvement in 12 nursing homes in a German
      city. METHODS: In the present study, the authors used an ex-post-facto design
      (survey methodology). Available written policies for routine pain assessment in
      residents >=65 years of age were reviewed and a standardized online survey
      completed by 151 of 349 nurses in 12 nursing home facilities was conducted
      between September 2010 and April 2011. RESULTS: Most of the included nursing
      homes provided written policies for pain assessment, and the majority of nurses
      reported that they assess and regularly reassess pain. However, observational
      tools for residents with severe cognitive impairment and written reassessment
      schedules were lacking in many facilities or were inconsistent. CONCLUSIONS:
      Essentially, pain assessment appeared to be feasible in the majority of the
      German nursing homes studied. However, the absence or inconsistency of
      reassessment schedules indicate that pain management guidelines should include a
      detailed and explicit reassessment schedule for the heterogenic needs of nursing
      home residents. For residents with severe cognitive impairment, assessment tools
      are needed that are simple to use and clearly indicate the presence or absence of
      pain.

PMID- 24851239
TI  - Development, implementation and evaluation of a pain management and palliative
      care educational seminar for medical students.
AB  - BACKGROUND: Despite calls for the development and evaluation of pain education
      programs during early medical student training, little research has been
      dedicated to this initiative. OBJECTIVES: To develop a pain management and
      palliative care seminar for medical students during their surgical clerkship and
      evaluate its impact on knowledge over time. METHODS: A multidisciplinary team of
      palliative care and pain experts worked collaboratively and developed the seminar
      over one year. Teaching methods included didactic and case-based instruction, as
      well as small and large group discussions. A total of 292 medical students
      attended a seminar during their third- or fourth-year surgical rotation. A 10
      item test on knowledge regarding pain and palliative care topics was administered
      before the seminar, immediately following the seminar and up to one year
      following the seminar. Ninety-five percent (n=277) of students completed the post
      test and 31% (n=90) completed the follow-up test. RESULTS: The mean pretest, post
      test and one-year follow-up test scores were 51%, 75% and 73%, respectively. Mean
      test scores at post-test and follow-up were significantly higher than pretest
      scores (all P<0.001). No significant difference was observed in mean test scores
      between follow-up and post-test (P=0.559), indicating that students retained
      knowledge gained from the seminar. CONCLUSIONS: A high-quality educational
      seminar using interactive and case-based instruction can enhance students'
      knowledge of pain management and palliative care. These findings highlight the
      feasibility of developing and implementing pain education material for medical
      students during their training.

PMID- 24851242
TI  - What have we learnt about the mechanisms of rapid water transport, ion rejection
      and selectivity in nanopores from molecular simulation?
AB  - Nanopores have demonstrated an extraordinary ability to allow water molecules to
      pass through their interiors at rates far exceeding expectations based on
      continuum theory. Moreover, simulation studies suggest that particular nanoscale
      pores have the potential to discriminate between water and salts as well as to
      distinguish between a range of different ion types. Some of the unusual features
      of transport in these nanopores have been elucidated with molecular dynamics
      simulation, specifically the spontaneous filling and rapid transport of water,
      the rejection of ions and the selection between ions. The main focus of this
      review, however, is the physical mechanisms which act to produce such remarkable
      behaviour at this scale, drawing on the many studies that have been conducted in
      the last decade. Since molecular dynamics simulations allow the motion of
      individual atoms to be followed over time, they have the potential to provide
      fundamental insight into the reasons why transport in nanoscale pores differs
      from expectations based on macroscopic theory. Gaining an understanding of the
      mechanisms of transport in these tiny pores should guide future experiments in
      this area aimed at developing novel technologies and improving existing membrane
      separation techniques.

PMID- 24851240
TI  - The antiallodynic action of pregabalin may depend on the suppression of spinal
      neuronal hyperexcitability in rats with spared nerve injury.
AB  - BACKGROUND: Pregabalin (PGB) is a novel antiepileptic drug and is also used as a
      first-line medication for the treatment of neuropathic pain. However, the
      mechanisms of its analgesic effects remain largely unknown. OBJECTIVES: To
      elucidate the mechanisms underlying the antiallodynic action of PGB in rats with
      neuropathic pain. METHODS: In a rat model of neuropathic pain induced by spared
      nerve injury, mechanical allodynia, as a behavioural sign of neuropathic pain,
      was assessed by measuring 50% paw withdrawal threshold with von Frey filaments.
      Activities of dorsal horn wide dynamic range (WDR) neurons were examined by
      extracellular electrophysiological recording in vivo. RESULTS: Spinal
      administration of PGB exerted a significant antiallodynic effect and a prominent
      inhibitory effect on the hypersensitivity of dorsal horn WDR neurons in rats with
      spared nerve injury. CONCLUSION: The antiallodynic action of PGB is likely
      dependent on the suppression of WDR neuron hyperexcitability in rats with
      neuropathic pain.

PMID- 24851243
TI  - High-performance and tailorable pressure sensor based on ultrathin conductive
      polymer film.

PMID- 24851244
TI  - Resident rounds: Part III: Multiple myeloma presenting as fulminant retiform
      purpura.
AB  - Retiform purpura secondary to underlying type 1 cryoglobulinemia can be a
      presenting sign of multiple myeloma. Severe pain may herald microvascular
      occlusion and impending ulceration. Recognizing the distinctive cutaneous and
      histopathologic features of this occlusive vasculopathy allows for timely
      diagnosis and treatment.

PMID- 24851245
TI  - Direct fabrication of hexagonally ordered ridged nanoarchitectures via dual
      interference lithography for efficient sensing applications.

PMID- 24851241
TI  - AID-induced remodeling of immunoglobulin genes and B cell  fate.
AB  - Survival and phenotype of normal and malignant B lymphocytes are critically
      dependent on constitutive signals by the B cell receptor (BCR) for antigen. In
      addition, either antigen ligation of the BCR or various mitogenic stimuli result
      in B cell activation and induction of activation-induced deaminase (AID). AID
      activity can in turn mediate somatic hypermutation (SHM) of immunoglobulin (Ig) V
      regions and also deeply remodel the Ig heavy chain locus through class switch
      recombination (CSR) or locus suicide recombination (LSR). In addition to changes
      linked to affinity for antigen, modifying the class/isotype (i.e. the structure
      and function) of the BCR or suddenly deleting BCR expression also modulates the
      fate of antigen-experienced B cells.

PMID- 24851246
TI  - Ex vivo reconstruction of the donor renal artery in renal transplantation: a case
      control study.
AB  - Transplantation of renal allografts with anatomic variability or injured
      vasculature poses a challenge to the transplanting surgeon but can be salvaged
      for transplantation with ex vivo bench reconstruction of the vasculature. We
      investigated whether renal allograft function is impaired in these reconstructed
      allografts; compared to the donor-matched, un-reconstructed allograft.
      Reconstructed allografts were transplanted into 60 patients at our institution
      between 1986 and 2012. A control group was selected from the matched pair of the
      recipient in deceased donor transplantation. We found no significant difference
      in the overall graft and patient survival rates (P = 1.0, P = 0.178). Serum
      creatinine levels were not significantly higher in the study group at 1, 3 and 12
      months postoperatively. There were two cases of vascular thrombosis in the study
      group that were not related to the ex vivo reconstruction. A significantly
      greater proportion of reconstructed patients were investigated with a colour
      duplex ultrasound postoperatively (0.007). Although we have demonstrated a higher
      index of suspicion of transplant failure in patients with a reconstructed
      allograft, this practice has proven to be a safe and useful technique with
      equivocal outcome when compared to normal grafts; increasing the organ pool
      available for transplantation.

PMID- 24851247
TI  - High-level expression of Aspergillus niger b-galactosidase in Ashbya gossypii.
AB  - Ashbya gossypii has been recently considered as a host for the expression of
      recombinant proteins. The production levels achieved thus far were similar to
      those obtained with Saccharomyces cerevisiae for the same proteins. Here, the b
      galactosidase from Aspergillus niger was successfully expressed and secreted by
      A. gossypii from 2-mm plasmids carrying the native signal sequence at higher
      levels than those secreted by S. cerevisiae laboratorial strains. Four different
      constitutive promoters were used to regulate the expression of bgalactosidase: A.
      gossypii AgTEF and AgGPD promoters, and S. cerevisiae ScADH1 and ScPGK1
      promoters. The native AgTEF promoter drove the highest expression levels of
      recombinant b-galactosidase in A. gossypii, leading to 2- and 8-fold higher
      extracellular activity than the AgGPD promoter and the heterologous promoters,
      respectively. In similar production conditions, the levels of active b
      galactosidase secreted by A. gossypii were up to 37 times higher than those
      secreted by recombinant S. cerevisiae and 2.5 times higher than those previously
      reported for the b-galactosidase-high producing S. cerevisiae NCYC869-A3/pVK1.1.
      The substitution of glucose by glycerol in the production medium led to a 1.5
      fold increase in the secretion of active b-galactosidase by A. gossypii.
      Recombinant b-galactosidase secreted by A. gossypii was extensively glycosylated,
      as are the native A. niger b-galactosidase and recombinant b-galactosidase
      produced by yeast. These results highlight the potential of A. gossypii as a
      recombinant protein producer and open new perspectives to further optimize
      recombinant protein secretion in this fungus.

PMID- 24851248
TI  - The Cardiostars Project: inspiring the   next generation of cardiologists.

PMID- 24851250
TI  - 50th anniversary of angioplasty.

PMID- 24851249
TI  - Bioinspired catechol-terminated self-assembled monolayers with enhanced adhesion
      properties.
AB  - The role of the catechol moiety in the adhesive properties of mussel proteins and
      related synthetic materials has been extensively studied in the last years but
      still remains elusive. Here, a simplified model approach is presented based on a
      self-assembled monolayer (SAM) of upward-facing catechols thiol-bound to
      epitaxial gold substrates. The orientation of the catechol moieties is confirmed
      by spectroscopy, which also showed lack of significant amounts of interfering o
      quinones. Local force-distance curves on the SAM measured by atomic force
      microscopy (AFM) shows an average adhesion force of 45 nN, stronger than that of
      a reference polydopamine coating, along with higher reproducibility and less
      statistical dispersion. This is attributed to the superior chemical and
      topographical homogeneity of the SAM coating. Catechol-terminated SAMs are also
      obtained on high-roughness gold substrates that show the ability to assemble
      magnetic nanoparticles, despite their lack of enhanced adhesion at the molecular
      level. Finally, the influence of the catechol group on the formation and quality
      of the SAM is explored both theoretically (molecular dynamics simulations) and
      experimentally using direct-write AFM lithography.

PMID- 24851251
TI  - Cardiac resynchronization therapy: are patients   being properly selected?

PMID- 24851252
TI  - RNAi-microsponges form through self-assembly of the organic and inorganic
      products of transcription.
AB  - Inorganic nanostructures have been used extensively to package nucleic acids into
      forms useful for therapeutic applications. Here we report that the two products
      of transcription, RNA and inorganic pyrophosphate, can self-assemble to form
      composite microsponge structures composed of nanocrystalline magnesium
      pyrophosphate sheets (Mg2P2O7*3.5H2O) with RNA adsorbed to their surfaces. The
      microsponge particles contain high loadings of RNA (15-21 wt.%) that are
      protected from degradation and can be obtained through a rolling circle mechanism
      as large concatemers capable of mediating RNAi. The morphology of the RNAi
      microsponges is influenced by the time-course of the transcription reaction and
      interactions between RNA and the inorganic phase. Previous work demonstrated that
      polycations can be used to condense RNAi microsponges into nanoparticles capable
      of efficient transfection with low toxicity. Our new findings suggest that the
      formation of these nanoparticles is mediated by the gradual dissolution of
      magnesium pyrophosphate that occurs in the presence of polycations. The simple
      one-pot approach for assembling RNAi microsponges along with their unique
      properties could make them useful for RNA-based therapeutics.

PMID- 24851253
TI  - [Paul Bornstein (1934-2013), a pioneer of matrix biology and pathology].

PMID- 24851254
TI  - Display of heterologous proteins on the Saccharomyces cerevisiae surface display
      system using a single constitutive expression vector.
AB  - In this study, we constructed a novel and simple yeast surface display system
      with a single expression vector. The newly established system uses a
      bidirectional expression vector carrying the AGA1 gene driven by the PGK1
      promoter in one direction and the AGA2-expression cassette driven by the TEF1
      promoter in the reverse direction, and uses the geneticin, a G418-resistant gene,
      as the selection marker for transformants. Because all the display elements are
      put into one expression vector, the new system is much simpler to use, and there
      is no need for any genetic modification of the host strains; therefore, the new
      system can be used in wild type as well as laboratory strains of Saccharomyces
      cerevisiae. The display efficiency of heterologous proteins using the new system
      has been confirmed by displaying enhanced green fluorescent protein and Eimeria
      tenella (a chicken protozoan parasite) microneme protein2 (EtMic2) on several S.
      cerevisiae strains. We also tested the new system with an aga2 mutant strain of
      S. cerevisiae. The results indicate that the native expressed Aga2 protein has no
      effect on the display efficiency of heterologous proteins.

PMID- 24851256
TI  - Measuring disparities in sanitation access: does the measure matter?
AB  - OBJECTIVE: Initiatives to monitor progress in health interventions like
      sanitation are increasingly focused on disparities in access. We explored three
      methodological challenges to monitoring changes in sanitation coverage across
      socio-economic and demographic determinants: (i) confounding by wealth indices
      including water and sanitation assets, (ii) use of individual urban and rural
      settings versus national wealth indices and (iii) child-level versus household
      level analyses. METHODS: Sanitation coverage by wealth for children and
      households across settings was estimated from recent Demographic and Health
      Surveys in six low-income countries. Household assignment to wealth quintiles was
      based on principal components analyses of assets. Concordance in household
      quintile assignment and estimated distribution of improved sanitation was
      assessed using two wealth indices differing by inclusion or exclusion of water
      and sanitation assets and independently derived for each setting. Improved
      sanitation was estimated using under five children and households. RESULTS:
      Wealth indices estimated with water, and sanitation assets are highly correlated
      with indices excluding them but can overstate disparities in sanitation access.
      Independently, derived setting wealth indices highly correlate with setting
      estimates of coverage using a single national index. Sanitation coverage and
      quintile disparities were consistently lower in household-level estimates.
      CONCLUSIONS: Standard asset indices provide a reasonably robust measure of
      disparities in improved sanitation, although overestimation is possible. Separate
      setting wealth quintiles reveal important disparities in urban areas, but
      analysis of setting quintiles using a national index is sufficient. Estimates and
      disparities in household-level coverage of improved sanitation can underestimate
      coverage for children under five.

PMID- 24851255
TI  - A novel approach for using dielectric spectroscopy to predict viable cell volume
      (VCV) in early process development.
AB  - Online monitoring of viable cell volume (VCV) is essential to the development,
      monitoring, and control of bioprocesses. The commercial availability of steam
      sterilizable dielectricspectroscopy probes has enabled successful adoption of
      this technology as a key noninvasive method to measure VCV for cell-culture
      processes. Technological challenges still exist, however. For some cell lines,
      the technique's accuracy in predicting the VCV from probepermittivity
      measurements declines as the viability of the cell culture decreases. To
      investigate the cause of this decrease in accuracy, divergences in predicted vs.
      actual VCV measurements were directly related to the shape of dielectric
      frequency scans collected during a cell culture. The changes in the shape of the
      beta dispersion, which are associated with changes in cell state, are quantified
      by applying a novel "area ratio" (AR) metric to frequency-scanning data from the
      dielectric-spectroscopy probes. The AR metric is then used to relate the shape of
      the beta dispersion to single-frequency permittivity measurements to accurately
      predict the offline VCV throughout an entire fed-batch run, regardless of cell
      state. This work demonstrates the possible feasibility of quantifying the shape
      of the beta dispersion, determined from frequency-scanning data, for enhanced
      measurement of VCV in mammalian cell cultures by applying a novel shape
      characterization technique. In addition, this work demonstrates the utility of
      using changes in the shape of the beta dispersion to quantify cell health.

PMID- 24851257
TI  - Depressive symptoms and suicide risk in older adults: value placed on autonomy as
      a moderator for men but not women.
AB  - Risk for suicide is elevated among older men. We examined whether value placed on
      autonomy amplifies the relation between depressive symptoms and suicide risk
      differently for older men and women. Participants were 98 community-dwelling
      older adults, M age 73.6 (SD = 8.6), 65.1% female, 93.1% White. Questionnaires
      measured suicide risk (SBQ-R), depressive symptoms (CESD), and value placed on
      autonomy (PSI-II autonomy). Among men, depressive symptoms were associated with
      suicide risk only when PSI-II autonomy was elevated. Among women, greater
      depressive symptoms were associated with suicide risk at all levels of PSI-II
      autonomy. Further research on attitudes toward autonomy is warranted.

PMID- 24851258
TI  - Meaning made of stress among veterans transitioning to college: examining unique
      associations with suicide risk and life-threatening behavior.
AB  - Meaning made of stress has been shown to be a unique predictor of mental and
      physical health. In this study, we examined the unique associations between two
      facets of meaning made of stress (comprehensibility and footing in the world) and
      suicide risk and life-threatening behavior among military veterans who have
      transitioned to college were examined, controlling for demographic factors,
      religiousness, combat-related physical injury, combat exposure, depressive
      symptoms, and posttraumatic stress symptoms. Findings suggest that
      comprehensibility (having "made sense" of a stressor) is uniquely associated with
      lower suicide risk and a lower likelihood of driving under the influence of drugs
      or alcohol and engaging in self-mutilating behaviors.

PMID- 24851259
TI  - Caseload, management and treatment outcomes of patients with hypertension and/or
      diabetes mellitus in a primary health care programme in an informal setting.
AB  - OBJECTIVE: In three primary health care clinics run by Medecins Sans Frontieres
      in the informal settlement of Kibera, Nairobi, Kenya, we describe the caseload,
      management and treatment outcomes of patients with hypertension (HT) and/or
      diabetes mellitus (DM) receiving care from January 2010 to June 2012. METHOD:
      Descriptive study using prospectively collected routine programme data. RESULTS:
      Overall, 1465 patients were registered in three clinics during the study period,
      of whom 87% were hypertensive only and 13% had DM with or without HT. Patients
      were predominantly female (71%) and the median age was 48 years. On admission,
      24% of the patients were obese, with a body mass index (BMI) > 30 kg/m2. Overall,
      55% of non-diabetic hypertensive patients reached their blood pressure (BP)
      target at 24 months. Only 28% of diabetic patients reached their BP target at 24
      months. For non-diabetic patients, there was a significant decrease in BP between
      first consultation and 3 months of treatment, maintained over the 18-month
      period. Only 20% of diabetic patients with or without hypertension achieved
      glycaemic control. By the end of the study period,1003 (68%) patients were alive
      and in care, one (<1%) had died, eight (0.5%) had transferred out and 453 (31%)
      were lost to follow-up. CONCLUSION: Good management of HT and DM can be achieved
      in a primary care setting within an informal settlement. This model of
      intervention appears feasible to address the growing burden of non-communicable
      diseases in developing countries.

PMID- 24851260
TI  - Systematic review of the proportion of pregnancy-related deaths attributed to HIV
      in population-based studies in sub-Saharan Africa.
AB  - OBJECTIVES: To estimate the proportion of pregnancy-related deaths attributed to
      HIV in population-based studies in sub-Saharan Africa, and to document the
      methods used to make such attribution. METHODS: Four databases were searched for
      studies on causes of maternal and pregnancy-related mortality published from 2003
      to June 2013. Data were extracted, and meta-analysis of proportions with random
      effects was used to obtain summary estimates. RESULTS: In the 19 studies found,
      the proportion of deaths attributed to HIV ranged from 0.0% to 27.0%. The summary
      proportion was 3.4% (95% confidence interval: 1.8-6.3), with high heterogeneity.
      Subregionally, the summary proportions were 1.1% (0.4-3.3%) in West Africa,
      4.5%(1.7-11.2%) in East Africa and 26.1% (21.9-30.7%) in Southern Africa.
      Criteria for assigning HIV as a cause of maternal death were rarely reported, and
      overall, methods were poor. CONCLUSIONS: The proportion of pregnancy
      related/maternal deaths attributed to HIV is substantially lower than modelled
      estimates, but comparisons are hampered by the absence of standard approaches.
      Clear guidelines on how to classify pregnancy-related deaths as attributable to
      HIV are urgently needed, so that the effect of the HIV epidemic on pregnancy
      related mortality can be monitored and action taken accordingly.

PMID- 24851261
TI  - RE: Applying the ICMJE authorship criteria to operational research in low-income
      countries: the need to engage programme managers and policy makers by Zachariah
      et al. (2013) TMIH 18, pp. 1025-1028.

PMID- 24851262
TI  - RE: Severe mental illness at ART initiation is associated with worse retention in
      care among HIV-infected Ugandan adults by JM Nachega et al. (2013), TMIH 18, pp
      53-57.

PMID- 24851263
TI  - RE: Severe mental illness at ART initiation is associated with worse retention in
      care among HIV-infected Ugandan adults by JM Nachega et al. (2013), TMIH 18, pp
      53-57.

PMID- 24851264
TI  - Reply to Giri and Long: Freeze-mediated expansion of mangroves does not depend on
      whether expansion is emergence or reemergence.

PMID- 24851265
TI  - Reply to Corbeil et al.: Dedifferentiation and multipotency.

PMID- 24851266
TI  - Sirolimus for non-progressive NF1-associated plexiform neurofibromas: an NF
      clinical trials consortium phase II study.
AB  - BACKGROUND: Patients with Neurofibromatosis Type 1 (NF1) have an increased risk
      of developing tumors of the central and peripheral nervous system, including
      plexiform neurofibromas (PN), which are benign nerve sheath tumors that are among
      the most debilitating complications of NF1. There are no standard treatment
      options for PN other than surgery, which is often difficult due to the extensive
      growth and invasion of surrounding tissues. Mammalian Target of Rapamycin (mTOR)
      acts as a master switch of cellular catabolism and anabolism and controls protein
      translation, angiogenesis, cell motility, and proliferation. The NF1 tumor
      suppressor, neurofibromin, regulates the mTOR pathway activity. Sirolimus is a
      macrolide antibiotic that inhibits mTOR activity. PROCEDURE: We conducted a 2
      stratum phase II clinical trial. In stratum 2, we sought to determine whether the
      mTOR inhibitor sirolimus in subjects with NF1 results in objective radiographic
      responses in inoperable PNs in the absence of documented radiographic progression
      at trial entry. RESULTS: No subjects had better than stable disease by the end of
      six courses. However, the children's self-report responses on health-related
      quality of life questionnaires indicated a significant improvement in the mean
      scores of the Emotional and School domains from baseline to 6 months of
      sirolimus. CONCLUSIONS: This study efficiently documented that sirolimus does not
      cause shrinkage of non-progressive PNs, and thus should not be considered as a
      treatment option for these tumors. This study also supports the inclusion of
      patient-reported outcome measures in clinical trials to assess areas of benefit
      that are not addressed by the medical outcomes.

PMID- 24851268
TI  - Application of translational science to the clinical problem of asthma. Preface.

PMID- 24851267
TI  - Adult testicular volume predicts spermatogenetic recovery after allogeneic HSCT
      in childhood and adolescence.
AB  - BACKGROUND: Testicular dysfunction and infertility are of major concern in long
      term survivors after allogeneic hematopoietic stem cell transplantation (HSCT).
      This study assesses predictive factors for very long-term testicular recovery
      after allogeneic HSCT in childhood and adolescence. PROCEDURE: Testicular volume,
      sperm production and long-term need of testosterone substitution were evaluated
      among 106 male survivors transplanted at Huddinge and Helsinki University
      Hospitals from 1978 through 2000, at a mean age of 8 +/- 4.6 years (range 1-17).
      A mean +/- SD of 13 +/- 4.8 years (range 4-28) had elapsed since their HSCT and
      the mean age of the participants was 22 +/- 6.0 years (range 12-42). An adult
      testicular volume was recorded in 74 patients at a mean age of 19 +/- 3.3 years
      (range 14-36). RESULTS: Recipients conditioned with busulfan-based regimens or
      regimens containing only cyclophosphamide had significantly larger adult
      testicular volumes (mean volume 18 ml and 16 ml vs. 9 ml, P < 0.00001,
      respectively) and lower serum levels of FSH (mean 9 IU and 5 IU vs. 19 IU, P <
      0.01 and 0.001, respectively) compared to those conditioned with total body
      irradiation (TBI). Multivariate analysis demonstrated that a non-leukemia
      diagnosis (P < 0.01) and adult testicular volume >= 15 ml (P < 0.03) positively
      impacted spermatogenetic recovery. CONCLUSIONS: A larger adult testicular volume,
      normal serum levels of FSH and spermatozoa detected in a majority of seminal
      fluids after busulfan-based or cyclophosphamide conditionings suggest very long
      term recovery of spermatogenesis after chemotherapy-based regimens. A simple
      measurement of adult testicular volume may help predict spermatogenetic potential
      among pediatric HSCT survivors.

PMID- 24851269
TI  - The spectrum of asthma: an introduction.

PMID- 24851271
TI  - Expression of P2X7 ATP receptor mediating the IL8 and CCL20 release in human
      periodontal ligament stem cells.
AB  - ATP is released by human periodontal ligament cells (hPDLCs) and has been shown
      to regulate PDL regeneration and responses to mechanical stress through
      activation of P2Y receptors. This nucleotide, however, has also been reported to
      trigger the pro-inflammatory cascade by inducing the maturation and/or release of
      chemokines/cytokines from various cell types mainly via P2X7 receptors. Much less
      is known on the possible role of ATP in stem cells deriving from PDL (hPDLSCs)
      which are considered to be a promising tool for cell-based therapy to restore
      lesions. Given the role played by P2X7 in pathophysiological conditions, in this
      study we investigated the expression of P2X7 ATP receptors in hPDLSCs. The
      results obtained showed that hPDLSCs express P2X7 receptors evaluated by means of
      cytofluorimetric, immunohistochemistry, reverse transcriptase-PCR, and Western
      blot analyses. P2X7 ligation by 2',3'-(benzoyl-4-benzoyl)-ATP (BzATP), a specific
      receptor agonist, was followed by an increase in intracellular Ca2+ and in the
      uptake of ethidium bromide. These effects were dramatically reduced by oxidized
      ATP (oATP), the P2X7 irreversible inhibitor, suggesting that the P2X7 is the
      functional receptor involved. At 24 h treatment of hPDLSCs with BzATP it enhanced
      the release of the pro-inflammatory agents IL8 and CCL20, without influencing
      cell viability. These effects were counteracted by pre-treating the cells with
      oATP or with A-740003, a selective and potent P2X7 competitive antagonist.
      Collectively, these results indicated that extracellular ATP mediate a pro
      inflammatory response via P2X7 receptors in hPDLSCs opening a further approach to
      control hPDLSCs behavior in their possible application as therapeutic tool.

PMID- 24851272
TI  - The complicated origins of our species.

PMID- 24851270
TI  - Osteoblasts protect AML cells from SDF-1-induced apoptosis.
AB  - The bone marrow provides a protective environment for acute myeloid leukemia
      (AML) cells that often allows leukemic stem cells to survive standard
      chemotherapeutic regimens. Targeting these leukemic stem cells within the bone
      marrow is critical for preventing relapse. We recently demonstrated that SDF-1, a
      chemokine abundant in the bone marrow, induces apoptosis in AML cell lines and in
      patient samples expressing high levels of its receptor, CXCR4. Here we show that
      a subset of osteoblast lineage cells within the bone marrow can protect AML cells
      from undergoing apoptosis in response to the SDF-1 naturally present in that
      location. In co-culture systems, osteoblasts at various stages of differentiation
      protected AML cell lines and patient isolates from SDF-1-induced apoptosis. The
      differentiation of the osteoblast cell lines, MC3T3 and W-20-17, mediated this
      protection via a cell contact-independent mechanism. In contrast, bone marrow
      derived mesenchymal cells, the precursors of osteoblasts, induced apoptosis in
      AML cells via a CXCR4-dependent mechanism and failed to protect AML cells from
      exogenously added SDF-1. These results indicate that osteoblasts in the process
      of differentiation potently inhibit the SDF-1-driven apoptotic pathway of CXCR4
      expressing AML cells residing in the bone marrow. Drugs targeting this protective
      mechanism could potentially provide a new approach to treating AML by enhancing
      the SDF-1-induced apoptosis of AML cells residing within the bone marrow
      microenvironment.

PMID- 24851273
TI  - Q & A: Suresh Jesuthasan.

PMID- 24851275
TI  - [What occupational exposures increase the risk of carpal tunnel syndrome?].

PMID- 24851274
TI  - Interaction of integrin beta4 with S1P receptors in S1P- and HGF-induced
      endothelial barrier enhancement.
AB  - We previously reported sphingosine 1-phosphate (S1P) and hepatocyte growth factor
      (HGF) augment endothelial cell (EC) barrier function and attenuate murine acute
      lung inury (ALI). While the mechanisms underlying these effects are not fully
      understood, S1P and HGF both transactivate the S1P receptor, S1PR1 and integrin
      beta4 (ITGB4) at membrane caveolin-enriched microdomains (CEMs). In the current
      study, we investigated the roles of S1PR2 and S1PR3 in S1P/HGF-mediated EC
      signaling and their associations with ITGB4. Our studies confirmed ITGB4 and
      S1PR2/3 are recruited to CEMs in human lung EC in response to either S1P (1 uM, 5
      min) or HGF (25 ng/ml, 5 min). Co-immunoprecipitation experiments identified an
      S1P/HGF-mediated interaction of ITGB4 with both S1PR2 and S1PR3. We then employed
      an in situ proximity ligation assay (PLA) to confirm a direct ITGB4-S1PR3
      association induced by S1P/HGF although a direct association was not detectable
      between S1PR2 and ITGB4. S1PR1 knockdown (siRNA), however, abrogated S1P/HGF
      induced ITGB4-S1PR2 associations while there was no effect on ITGB4-S1PR3
      associations. Moreover, PLA confirmed a direct association between S1PR1 and
      S1PR2 induced by S1P and HGF. Finally, silencing of S1PR2 significantly
      attenuated S1P/HGF-induced EC barrier enhancement as measured by transendothelial
      resistance while silencing of S1PR3 significantly augmented S1P/HGF-induced
      barrier enhancement. These results confirm an important role for S1PR2 and S1PR3
      in S1P/HGF-mediated EC barrier responses that are associated with their complex
      formation with ITGB4. Our findings elucidate novel mechanisms of EC barrier
      regulation that may ultimately lead to new therapeutic targets for disorders
      characterized by increased vascular permeability including ALI.

PMID- 24851276
TI  - [Responsiveness to the change in the Work Performance Questionnaire (Spanish
      version) in a working population].
AB  - The objective of this paper is to examine the responsiveness of the Work Role
      Functioning Questionnaire (Spanish version) ( WRFQ-SpV) so that it could be used
      in evaluative studies. For this purpose a longitudinal survey was performed.
      Combinations of distributions-and anchor- based approaches were used. Five
      hypotheses were tested, examining validity of change scores. The consensus-based
      standards for the selection of health status measurement instruments (COSMIN)
      guided the study design. One hundred and two participants (mean age, 47.3 years;
      SD=10.3 years) completed the WRFQ-SpV twice, within a mean interval of 3.7 (
      SD=1.8) months. Four hypotheses were confirmed and one was rejected . It was
      verified that the WRFQ-SpV was able to detect (true) changes over time. In
      conclusion, suggestive evidence about the possible use if the WRFQ-SpV with
      evaluative purposes was provided. More research is needed to examine the
      instrument responsiveness for groups whose health is stable or deteriorates.

PMID- 24851277
TI  - Author's reply: To PMID 24222284.

PMID- 24851278
TI  - Author's reply: To PMID 24413503.

PMID- 24851279
TI  - Author's reply: To PMID 23798639.

PMID- 24851280
TI  - Author's reply: To PMID 23798633.

PMID- 24851281
TI  - Response to 'Statement from the European Society of Vascular Surgery and the
      World Federation of Vascular Surgery Societies' Inter-Society Consensus Document
      (TASC) III and International Standards for Vascular Care (ISVaC).

PMID- 24851282
TI  - UTS2R gene polymorphisms are associated with fatty  acid composition in Japanese
      beef cattle.
AB  - Fatty acid composition of beef adipose tissue is one of its important traits
      because a high proportion of monounsaturated fatty acid is related to favorable
      beef flavor and tenderness. In this study, we searched polymorphisms in full
      length coding DNA sequence of urotensin 2 recepter and investigated the effects
      on fatty acid composition (C14:0, C14:1, C16:0, C16:1, C18:0, C18:1, C18:2,
      monounsaturated fatty acid, saturated fatty acid). Eight single nucleotide
      polymorphisms (SNP) were identified by sequence comparison among eight animals,
      including five Japanese Black and three Holstein cattle. One of these SNP
      (c.866C>T) was predicted to cause amino acid substitutions (P289L) and the other
      seven synonymous SNP, including c.267C>T, were presumed to be in linkage
      disequilibrium. Therefore we selected two SNP (c.267C>T and c.866C>T) for further
      analysis. We investigated associations between these genotypes and fatty acid
      composition in three Japanese Black populations (n=560, 245 and 287) and a
      Holstein population (n=202). Tukey-Kramer's honestly significant difference test
      revealed that CC genotype in c.267C>T indicated lower C14:0 and higher C18:1 than
      the other genotypes in Japanese Black cattle and CC genotype in c.866C>T showed
      lower C16:1 than CT genotype in Holstein cattle (P<0.05). These results suggested
      that these genotypes would contribute to production of high-grade meat as
      selection markers in beef cattle.

PMID- 24851283
TI  - Direct visualization of membrane architecture of myelinating cells in transgenic
      mice expressing membrane-anchored EGFP.
AB  - Myelinogenesis is a complex process that involves substantial and dynamic changes
      in plasma membrane architecture and myelin interaction with axons. Highly
      ramified processes of oligodendrocytes in the central nervous system (CNS) make
      axonal contact and then extrapolate to wrap around axons and form multilayer
      compact myelin sheathes. Currently, the mechanisms governing myelin sheath
      assembly and axon selection by myelinating cells are not fully understood. Here,
      we generated a transgenic mouse line expressing the membrane-anchored green
      fluorescent protein (mEGFP) in myelinating cells, which allow live imaging of
      details of myelinogenesis and cellular behaviors in the nervous systems. mEGFP
      expression is driven by the promoter of 2'-3'-cyclic nucleotide 3'
      phosphodiesterase (CNP) that is expressed in the myelinating cell lineage. Robust
      mEGFP signals appear in the membrane processes of oligodendrocytes in the CNS and
      Schwann cells in the peripheral nervous system (PNS), wherein mEGFP expression
      defines the inner layers of myelin sheaths and Schmidt-Lanterman incisures in
      adult sciatic nerves. In addition, mEGFP expression can be used to track the
      extent of remyelination after demyelinating injury in a toxin-induced
      demyelination animal model. Taken together, the membrane-anchored mEGFP
      expression in the new transgenic line would facilitate direct visualization of
      dynamic myelin membrane formation and assembly during development and process
      remodeling during remyelination after various demyelinating injuries.

PMID- 24851311
TI  - [Weapons of mass destruction].

PMID- 24851312
TI  - Dr David Stather.

PMID- 24851313
TI  - John Edwin Horton 1931-2012.

PMID- 24851284
TI  - The cerebellum and addiction: insights gained from neuroimaging research.
AB  - Although cerebellar alterations have been consistently noted in the addiction
      literature, the pathophysiology of this link remains unclear. The cerebellum is
      commonly classified as a motor structure, but human functional neuroimaging along
      with clinical observations in cerebellar stroke patients and anatomical tract
      tracing in non-human primates suggests its involvement in cognitive and affective
      processing. A comprehensive literature search on the role of the cerebellum in
      addiction was performed. This review article (1) considers the potential role of
      the cerebellum in addiction; (2) summarizes the cerebellar structural alterations
      linked to addiction; (3) presents the functional neuroimaging evidence linking
      the cerebellum with addiction; and (4) proposes a model for addiction that
      underscores the role of the cerebellum. The data implicate the cerebellum as an
      intermediary between motor and reward, motivation and cognitive control systems,
      as all are relevant etiologic factors in addiction. Furthermore, consideration of
      these findings could contribute to deeper and more sophisticated insights into
      normal reward and motivational function. The goal of this review is to spread
      awareness of cerebellar involvement in addictive processes, and to suggest a
      preliminary model for its potential role.

PMID- 24851314
TI  - Barbara Farnsworth Heslop Immunologist, academic.

PMID- 24851315
TI  - TRICARE revision to CHAMPUS DRG-based payment system, pricing of hospital claims.
      Final rule.
AB  - This Final rule changes TRICARE's current regulatory provision for inpatient
      hospital claims priced under the DRG-based payment system. Claims are currently
      priced by using the rates and weights that are in effect on a beneficiary's date
      of admission. This Final rule changes that provision to price such claims by
      using the rates and weights that are in effect on a beneficiary's date of
      discharge.

PMID- 24851316
TI  - Proceedings of the 23rd International Conference on Information Processing in
      Medical Imaging, June 28-July 3, 2013, Asilomar, CA.

PMID- 24851317
TI  - [Oral infection and rheumatic diseases-editorial].

PMID- 24851318
TI  - [Catheter related septic central venous thrombosis of the superior vena cava and
      right atrium: case reports-editorial].

PMID- 24851319
TI  - Obesity: progress and challenges.

PMID- 24851320
TI  - [Catheter related septic central venous thrombosis of the superior vena cava and
      right atrium: case reports-editorial].

PMID- 24851321
TI  - A legal review of autism, a syndrome rapidly gaining wide attention within our
      society.

PMID- 24851322
TI  - The FDA and the pharmaceutical industry: is regulation contributing to drug
      shortage?

PMID- 24851323
TI  - Avoiding contractual liability to baseball players who have used performance
      enhancing drugs: can we knock it out of the park?

PMID- 24851324
TI  - Enhanced stabilization of digested sludge during long-term storage in anaerobic
      lagoons.
AB  - The goal of this work was to study changes in anaerobically stored digested
      sludge under different lengths of storage time to evaluate the quality of final
      product biosolids. The analyses of collected data suggest the organic matter
      degradation occurrence in the anaerobic environment of the lagoon approximately
      within the first year. After that, the degradation becomes very slow, which is
      likely caused by unfavorable environmental conditions. The performance of lagoon
      aging of digested sludge was also compared to the performance of lagoon aging of
      anaerobically digested and dewatered sludge. It was concluded that both of these
      processes result in biosolids of comparative quality and that the former provides
      more economical solution to biosolids handling by eliminating the need for
      mechanical dewatering.

PMID- 24851325
TI  - Removal of copper ions from water using epichlorohydrin cross-linked beta
      cyclodextrin polymer: characterization, isotherms and kinetics.
AB  - Beta-cyclodextrin (beta-CD) cross-linked with epichlorohydrin to form water
      insoluble beta-cyclodextrin polymer (beta-CDP) has been shown to be an effective
      sorbent for sorption of organic particles, but the sorption of copper (Cu2+) in
      aqueous solutions by beta-CDP has not been conducted. The objective of this study
      was to explore the sorption mechanism of beta-CDP for copper. The effects of
      different experimental conditions such as pH, ionic strength, contact time, and
      temperature were inspected using a batch method. In addition, binding scheme was
      estimated by using Fourier transform infrared (FTIR) spectroscopy, Xray
      photoelectron spectroscopy (XPS), a scanning electron microscope (SEM), and
      Brunauer-Emmett-Teller (BET) analysis. The adsorption of Cu2+ was observed to be
      higher at pH 6.0. The kinetic study revealed that the adsorption is fitted well
      by the pseudo-second-order kinetic model. The maximum binding of Cu2+ was
      estimated to be 111.11 mg/g through the Langmuir isotherm model--much higher than
      the existing sorption technologies. Hence, the adsorption-desorption trends of
      epichlorohydrin cross-linked with beta-CD, along with its good recyclability,
      establish an alternative, effective, and novel remediation technology for the
      removal of Cu2+ from aqueous solutions.

PMID- 24851326
TI  - Nitrogen removal from wastewater by an aerated subsurface-flow constructed
      wetland in cold climates.
AB  - The objective of this study was to assess the role of cyclic aeration,
      vegetation, and temperature on nitrogen removal by subsurface-flow engineered
      wetlands. Aeration was shown to enhance total nitrogen and ammonia removal and to
      enhance removal of carbonaceous biochemical oxygen demand, chemical oxygen
      demand, and phosphorus. Effluent ammonia and total nitrogen concentrations were
      significantly lower in aerated wetland cells when compared with unaerated cells.
      There was no significant difference in nitrogen removal between planted and
      unplanted cells. Effluent total nitrogen concentrations ranged from 9 to 12 mg
      N/L in the aerated cells and from 23 to 24 mg N/L in unaerated cells. Effluent
      ammonia concentrations ranged from 3 to 7 mg N/L in aerated wetland cells and
      from 22 to 23 mg N/L in unaerated cells. For the conditions tested, temperature
      had only a minimal effect on effluent ammonia or total nitrogen concentrations.
      The tanks-in-series and the PkC models predicted the general trends in effluent
      ammonia and total nitrogen concentrations, but did not do well predicting short
      term variability. Rate coefficients for aerated systems were 2 to 10 times
      greater than those for unaerated systems.

PMID- 24851327
TI  - Nitrogen and chemical oxygen demand removal from septic tank wastewater in
      subsurface flow constructed wetlands: substrate (cation exchange capacity)
      effects.
AB  - The current article focuses on chemical oxygen demand (COD) and nitrogen
      (ammonium and nitrate) removal performance from synthetic human wastewater as
      affected by different substrate rocks having a range of porosities and cation
      exchange capacities (CECs). The aggregates included lava rock, lightweight
      expanded shale, meta-basalt (control), and zeolite. The first three had CECs of 1
      to 4 mequiv/100 gm, whereas the zeolite CEC was much greater (-80 mequiv/100 gm).
      Synthetic wastewater was gravity fed to each constructed wetland system,
      resulting in a 4-day retention time. Effluent samples were collected, and COD and
      nitrogen species concentrations measured regularly during four time periods from
      November 2008 through June 2009. Chemical oxygen demand and nitrogen removal
      fractions were not significantly different between the field and laboratory
      constructed wetland systems when corrected for temperature. Similarly, overall
      COD and nitrogen removal fractions were practically the same for the aggregate
      substrates. The important difference between aggregate effects was the zeolite's
      ammonia removal process, which was primarily by adsorption. The resulting single
      stage nitrogen removal process may be an alternative to nitrification and
      denitrification that may realize significant cost savings in practice.

PMID- 24851328
TI  - Microbial community analysis of a single chamber microbial fuel cell using potato
      wastewater.
AB  - Microbial fuel cells (MFCs) convert chemical energy to electrical energy via bio
      electrochemical reactions mediated by microorganisms. This study investigated the
      diversity of the microbial community in an air cathode single chamber MFC that
      used potato-process wastewater as substrate. Terminal restriction fragment length
      polymorphism results indicated that the bacterial communities on the anode,
      cathode, control electrode, and MFC bulk fluid were similar, but differed
      dramatically from that of the anaerobic domestic sludge and potato wastewater
      inoculum. The 16S ribosomal DNA sequencing results showed that microbial species
      detected on the anode were predominantly within the phyla of Proteobacteria,
      Firmicutes, and Bacteroidetes. Fluorescent microscopy results indicated that
      there was a clear enhancement of biofilm formation on the anode. Results of this
      study could help improve understanding of the complexity of microbial communities
      and optimize the microbial composition for generating electricity by MFCs that
      use potato wastewater.

PMID- 24851329
TI  - Fate of heavy metals and evaluation of eutrophication in a wetland-reservoir
      system.
AB  - The fate of heavy metals (Cd, Cr, Cu, Ni, Pb, and Zn) in the water column,
      sediment, and macrophytic plants as well as a total phosphorus eutrophication
      model were evaluated by a field monitoring program in the LungLuanTan wetland
      reservoir system in Taiwan. Zinc and Cd were found to have the highest and lowest
      partition coefficients, respectively. The levels of heavy metals in the sediment
      of the wetland were highest in the dry season. In fresh plant tissues and
      sediment, Cd had the highest bioconcentration factor during the study period.
      Furthermore, the results obtained using the total phosphorus model with time
      variable volumes for reservoir eutrophication and observed values were in
      reasonable agreement. Based on the modeling results, appropriate watershed
      management strategies are proposed to restore the wetland-reservoir water
      quality.

PMID- 24851330
TI  - Feasibility of using NaCl to reduce membrane fouling in anaerobic membrane
      bioreactors.
AB  - The objective of this research study is to assess the feasibility of naturally
      occurring Na+ ions in wastewater as a possible coagulant to control the fouling
      of AnMBR under high salinity conditions. A multi-bladed stirrer was installed in
      the reactor, which aimed at providing a good mixing condition for inducing
      coagulation. The rotation speed of the stirrer was set at 30 rpm for achieving
      the coagulation effect. A sludge was cultured in a saline environment with sodium
      concentration as high as 13 g/L. It was observed that, the applied conditions
      could not provide a high saline sludge with a good filterability. In addition,
      results of Fourier transform infrared spectroscopy showed that the functional
      groups of the cake layer formed by the saline sludge was similar to that of non
      saline sludge, therefore, the high salinity should promote the formation of a gel
      layer.

PMID- 24851331
TI  - Nonlinear programming technique for analyzing flocculent settling data.
AB  - The traditional graphical approach for drawing iso-concentration curves to
      analyze flocculent settling data and design sedimentation basins poses
      difficulties for computer-based design methods. Thus, researchers have developed
      empirical approaches to analyze settling data. In this study, the ability of five
      empirical approaches to fit flocculent settling test data is compared. Particular
      emphasis is given to compare rule-based SETTLE and rule-based nonlinear
      programming (NLP) techniques as a viable alternative to the modeling methods of
      Berthouex and Stevens (1982), San (1989), and Ozer (1994). Published flocculent
      settling data are used to test the suitability of these empirical approaches. The
      primary objective, however, is to determine if the results of a NLP optimization
      technique are more reliable than those of other approaches. For this,
      mathematical curve fitting is conducted and the modeled concentration data are
      graphically compared to the observed data. The design results in terms of average
      solid removal efficiency as a function of detention times are also compared.
      Finally, the sum of squared errors values from these approaches are compared. The
      results indicate a strong correlation between observed and NLP modeled
      concentration data. The SETTLE and NLP approaches tend to be more conservative at
      lower retention times and less conservative at longer retention times. The SETTLE
      approach appears to be the most conservative. In terms of sum of squared errors
      values, NLP appears to be rank number one (i.e., best model) for eight data sets
      and number two for six data sets among 15 data sets. Therefore, NLP is
      recommended for analyzing flocculent settling data as a logical extension of
      other approaches. The NLP approach is further recommended as it is an
      optimization technique and uses conventional mathematical algorithms that can be
      solved using widely available software such as EXCEL and LINGO.

PMID- 24851332
TI  - Kinetic and thermodynamic studies on the removal of oil from water using
      superhydrophobic kapok fiber.
AB  - In this paper, an oil sorbent based on superhydrophobic kapok fiber fabricated by
      the sol-gel method was used for the selective sorption of oil from the surface of
      artificial seawater. The effects of process parameters such as seawater pH,
      seawater temperature, and contact time on the extent of oil sorption were
      investigated. The as-prepared fiber showed higher oil sorption capacity than raw
      fiber in both the trenchant acid and alkaline seawater environment. Results of
      the kinetic studies show that the sorption process follows pseudo-second-order
      reaction kinetics. The thermodynamic investigations demonstrate that the sorption
      process is spontaneous and endothermic. In addition, the as-prepared fiber can
      float on the water surface after the sorption of oil, which facilitates the post
      processing of oil-loaded fiber. The modified fiber might provide a simple method
      for the removal and collection of oil on the water surface.

PMID- 24851333
TI  - Evaluation of activated sludge for biodegradation of propylene glycol as an
      aircraft deicing fluid.
AB  - Aircraft deicing fluid used at airport facilities is often collected for
      treatment or disposal in order to prevent serious ecological threats to nearby
      surface waters. This study investigated lab scale degradation of propylene
      glycol, the active ingredient in a common aircraft deicing fluid, by way of a
      laboratory-scale sequencing batch reactor containing municipal waste water
      treatment facility activated sludge performing simultaneous organic carbon
      oxidation and nitrification. The ability of activated sludge to remove propylene
      glycol was evaluated by studying the biodegradation and sorption characteristics
      of propylene glycol in an activated sludge medium. The results indicate sorption
      may play a role in the fate of propylene glycol in AS, and the heterotrophic
      bacteria readily degrade this compound. Therefore, a field deployable bioreactor
      may be appropriate for use in flight line applications.

PMID- 24851334
TI  - Effect of wildfires on physicochemical changes of watershed dissolved organic
      matter.
AB  - Physicochemical characterization of dissolved organic carbon (DOC) provides
      essential data to describe watershed characteristics after drastic changes caused
      by wildfires. Post-fire watershed behavior is important for water source
      selection, management, and drinking water treatment optimization. Using ash and
      other burned vegetation fragments, a leaching procedure was implemented to
      describe physicochemical changes to watershed DOC caused by wildfires. Samples
      were collected after the 2007 and 2009 wildfires near Santa Barbara, California.
      Substantial differences in size distribution (measured by ultrafiltration),
      polarity (measured by polarity rapid assessment method), and the origin of
      leached DOC (measured by fluorescence) were observed between burned and unburned
      sites. Recently burned ash had 10 times the DOC leaching potential, and was
      dominated by large size fragments, compared to weathered 2-year-old ash. Charged
      DOC fractions were found to positively correlate with DOC size, whereas
      hydrophobic and hydrophilic DOC fractions were not. Proteins were only observed
      in recently burned ash and were indicative of recent post-fire biological
      activity.

PMID- 24851335
TI  - [Skills, competences, and attitudes. Everything?].

PMID- 24851336
TI  - [The nurse at the hospital].

PMID- 24851337
TI  - [A. J. Cronin: a physician writer in defense of nursing].

PMID- 24851338
TI  - [Triage clinic practice. Application of different systems of triage].
AB  - INTRODUCTION: Emergency Services in Spain are suffering from a permanent increase
      in demand, making it difficult to fast and efficient they are required. The new
      situation has led to a transformation of the emergency departments with
      structural, organizational and functional changes, being triage system one of the
      key points. Triage systems are intended primarily to classify patients according
      to the level of urgency in order to prioritize the order of attendance, in
      addition to defining the most appropriate location, predict clinical outcomes and
      resource needs of patients, which contribute to the management of Emergency
      Service. DEVELOPMENT: Five models are currently recognized triage with a wide
      deployment among countries: Australian Triage Scale, Manchester Triage System,
      Emergency Severity Index, Canadian Triage and Acuity Scale, and Spanish Triage
      System, created from the Andorran Model of Triage (MAT). DISCUSSION: In
      Catalonia, we propose the implementation of a unique triage mode, MAT, and is
      considered a key intervention to improve the quality of care for emergencies, but
      from this deployment would be necessary to know if the results confirm this is a
      good system for managing all emergency services. CONCLUSION: Triage has become
      the hallmark of the hospital Emergency department who applies. It is an objective
      tool used to evaluate and improve the operation of the Emergency Services.

PMID- 24851339
TI  - [Emergency department triage: independent nursing intervention?].
AB  - The branch hospital triage aimed at, as well as exercised by nurses, has evolved
      to meet their needs to organize and make visible the nurses' duties. However, it
      is still not properly considered as independent nursing intervention. Evidencing
      practice triage nurse in hospital as experienced by their protagonists disclosed
      the possible causes of this paradoxical competence. In a sample of 41 nurses, of
      the 52 possible with previous experience in hospital triage in the Emergency
      Department of the Hospital General Dr. Jose Molina Orosa in Lanzarote, the nurses
      themselves carried out an opinion survey that group together statements about
      different aspects of the triaje nurse. In its results, 65.8% of those polled
      thought the triaje nursing training to be deficient and even though nearly half
      48.7%, was considered competent to decide the level of emergency, 46.3% disagreed
      to take this task part of their duty. It is conclusive that the training received
      in hospital triage, regulated and sustained, is deficient, that is the main
      reason why professionals have their doubts to take on an activity they are not
      familiar with. Triage systems do not record the entire outcome of the nursing
      work and nursing methodology does not seem to be quite indicative for this task.

PMID- 24851340
TI  - [Triage evaluation making in a pediatric emergency department of a tertiary
      hospital].
AB  - OBJECTIVE: Evaluation triage level assignments depending level of the
      professionals' education and experience in the unit. METHOD: This was a
      retrospective and observational study to triages making from January to March
      2012 in Pediatric Emergency Department of tertiary hospital in Madrid. The
      collection data included variables from Pediatric Canadian Triage with five
      levels, triage tool using in the unit. RESULTS: 6443 triages were evaluated. The
      most common mistakes was: not to register pain level, 1445 (22.4%); not to
      register hydration level, 377 (5.9%); principal symptoms inappropriate, 232
      (3.6%). Didn't indicate pain level 140 (5.6%) nurses with 12 hour formal training
      on triage; 492 (14.5%) with training in the unit, and 92 (16.3%) without training
      in the last year (p < 0.001). Among the nurses working in the unit more than 7
      years did not register pain level 472 (12.3%), identified inappropriate principal
      symptoms 197 (5%) and did not register hydration level 296 (7.7%). CONCLUSIONS:
      The triage education favors better adaptation in the triage assignment. The most
      common errors are: not to register level pain and hydration when it's needed for
      the principal symptoms.

PMID- 24851341
TI  - [The birthing ball: rediscovering a non pharmacological resource of great
      importance in the birth process].
AB  - Advances occurred in recent years in obstetrics show that the free movement of
      the pelvis during labour decreases pain and facilitates the birth of the newborn.
      Nowadays, many techniques have effective non pharmacological relief in pain
      during labour. The birthing ball (BB) is one of them, closely linked to freedom
      of movement, the pelvic tilt and vertical feeding; it has shown a decrease in
      anxiety and pain during the birthing process and increased rate of normal
      deliveries. The BB does not replace other non-pharmacological techniques during
      the period of expansion, but can complement it, thereby improving their
      effectiveness. Not shown any harmful effects associated with the use of the BB
      both the mother and the newborn. As health professionals, we must know how to use
      and the benefits that are associated with the BB, to offer it as an effective
      method of pain relief in labour available to us.

PMID- 24851343
TI  - Preface. Interesting and wide-ranging assortment of theoretical and research
      perspectives that typify the important issues in developmental psychology.

PMID- 24851342
TI  - [Herpes zoster treated with Bach flowers].
AB  - This report describes the case of a man of 78 years old who suffers multiple
      disorders. This man was attended by a communitarian nurse in a health care
      center. The patient was treated with floral therapy, and the evolution of the
      patient, the prescriptions (oral and topic) and the interventions of the nurse
      are explained with detail in the report. METHODOLOGY: Visits at the health center
      and a monitoring of the injuries. CONCLUSIONS: The result of the treatment was a
      short recovery time for the different injuries. The implication of the family and
      the patient himself in the treatment helped to get these good results and reduce
      the anxiety of the patient.

PMID- 24851344
TI  - Demystifying internalization and socialization: linking conceptions of how
      development happens to organismic-developmental theory.
AB  - Internalization and socialization are central constructs in developmental
      psychology for explaining and investigating how development happens through
      social interaction. There has been and continues to be much debate about how to
      conceptualize and investigate these processes. The ways in which internalization
      and socialization promote development have also been difficult to identify. The
      goal of this chapter is to offer a way of clarifying what happens during
      internalization and socialization by linking them to a clear conceptualization of
      development. The chapter first provides an overview of internalization and
      socialization theory and research. This review indicates that the focus on how
      development happens through social interaction has taken attention away from
      specifying the developmental changes that occur through social interaction. It is
      argued that understanding internalization and socialization can be enhanced by
      linking them to a clear definition of development, such as the one provided by
      organismic-developmental theory. According to organismic-developmental theory,
      developmental change is distinguished from any change that may occur over time.
      Rather, development is defined in terms of the differentiation and integration of
      action components in relation to cultural values and expectations for
      development. After explicating organismic-developmental theory's key claims, some
      implications of utilizing it for advancing an understanding of internalization
      and socialization are discussed. The chapter ends with suggestions for future
      research on internalization, socialization, and development.

PMID- 24851345
TI  - Adolescents' theories of the commons.
AB  - Drawing from research on civic engagement and environmental commitment, we make a
      case for the processes inherent in how adolescents' ideas about the commons
      (those things that bind a polity together) develop. Engagement in the public
      realm with a plethora of perspectives and a goal of finding common ground is
      fundamental. Adolescents participate in the public realm through mini-polities
      (e.g., schools, community organizations). Practices in those settings can
      reinforce or challenge dominant political narratives. Special attention is given
      to the natural environment as a commons that transcends generations and to the
      opportunities in schools and in community partnerships that enable adolescents to
      realize their interdependence with nature and to author decisions about the
      commons.

PMID- 24851346
TI  - LGB-parent families: the current state of the research and directions for the
      future.
AB  - Over the past several decades, lesbian, gay, and bisexual (LGB) parenting has
      grown more visible. Alongside this enhanced visibility, research on the
      experiences of LGB parents and their children has proliferated. The current
      chapter addresses this research, focusing on several main content areas: family
      building by LGB people, the transition to parenthood for LGB parents, and
      functioning and experiences of LGB parents and their children. In the context of
      discussing what we know about LGB-parent families, we highlight gaps in our
      knowledge and point to key areas that future research should aim to answer,
      including how race, ethnicity, social class, and geographic factors shape the
      experiences of LGB-parent families.

PMID- 24851347
TI  - The impact of parental deployment to war on children: the crucial role of
      parenting.
AB  - It is estimated that approximately 2 million children have been affected by
      military deployment, yet much of what is known about the adjustment of children
      experiencing a parent's combat deployment has emerged only within the past 5-10
      years. The extant literature on associations of parental deployment and
      children's adjustment is briefly reviewed by child's developmental stage.
      Applying a family stress model to the literature, we propose that the impact of
      parental deployment and reintegration on children's adjustment is largely
      mediated by parenting practices. Extensive developmental literature has
      demonstrated the importance of parenting for children's resilience in adverse
      contexts more generally, but not specifically in deployment contexts. We review
      the sparse literature on parenting in deployed families as well as emerging data
      on empirically supported parenting interventions for military families. An agenda
      for future research in this area is proffered.

PMID- 24851348
TI  - Shining light on infants' discovery of structure.
AB  - Learning and discovery seem often to begin with noting patterns. Human infants
      are skilled at pattern detection, even patterns only definable at an abstract
      level, which is key to their acquisition of complex knowledge systems such as
      language and music. However, research examining infants' abstract rule learning
      has generated inconsistent results. We propose that apparent domain differences
      in infants' abstract rule learning may be the result of extraneous stimulus
      variation and discrepancies in the methodologies employed across studies probing
      this skill. We discuss how a behavioral methodology indexing infants' online
      learning would be valuable in furthering understanding of infants' (as well as
      adults') abstract rule learning and its neurophysiological concomitants. We
      outline current research aimed at developing such an index, and we propose future
      research, pairing such techniques with neurophysiological methods, aimed at
      shining more light on human skill at discovering structure.

PMID- 24851349
TI  - Development of adaptive tool-use in early childhood: sensorimotor, social, and
      conceptual factors.
AB  - Tool-use is specialized in humans, and juvenile humans show much more prolific
      and prodigious tool-use than other juvenile primates. Nonhuman primates possess
      many of the basic motor and behavioral capacities needed for manual tool-use:
      perceptual-motor specialization, sociocultural practices and interactions, and
      abstract conceptualization of kinds of functions, both real and imagined. These
      traits jointly contribute to the human specialization for tool-using. In
      particular, from 2 to 5 years of age children develop: (i) more refined motor
      routines for interacting with a variety of objects, (ii) a deeper understanding
      and awareness of the cultural context of object-use practices, and (iii) a
      cognitive facility to represent potential dynamic human-object interactions. The
      last trait, which has received little attention in recent years, is defined as
      the ability to form abstract (i.e., generalizable to novel contexts)
      representations of kinds of functions, even with relatively little training or
      instruction. This trait might depend not only on extensive tool-using experience
      but also on developing cognitive abilities, including a variety of cognitive
      flexibility: specifically, imagistic memory for event sequences incorporating
      causal inferences about mechanical effects. Final speculations point to a
      possible network of neural systems that might contribute to the cognitive
      capacity that includes sensorimotor, sensory integration, and prefrontal cortical
      resources and interconnections.

PMID- 24851350
TI  - Edge replacement and minimality as models of causal inference in children.
AB  - Recently, much research has focused on causal graphical models (CGMs) as a
      computational-level description of how children represent cause and effect. While
      this research program has shown promise, there are aspects of causal reasoning
      that CGMs have difficulty accommodating. We propose a new formalism that amends
      CGMs. This edge replacement grammar formalizes one existing and one novel
      theoretical commitment. The existing idea is that children are determinists, in
      the sense that they believe that apparent randomness comes from hidden
      complexity, rather than inherent nondeterminism in the world. The new idea is
      that children think of causation as a branching process: causal relations grow
      not directly from the cause, but from existing relations between the cause and
      other effects. We have shown elsewhere that these two commitments together, when
      formalized, can explain and quantitatively fit the otherwise puzzling effect of
      nonindependence observed in the adult causal reasoning literature. We then test
      the qualitative predictions of this new formalism on children in a series of
      three experiments.

PMID- 24851351
TI  - Applying risk and resilience models to predicting the effects of media violence
      on development.
AB  - Although the effects of media violence on children and adolescents have been
      studied for over 50 years, they remain controversial. Much of this controversy is
      driven by a misunderstanding of causality that seeks the cause of atrocities such
      as school shootings. Luckily, several recent developments in risk and resilience
      theories offer a way out of this controversy. Four risk and resilience models are
      described, including the cascade model, dose-response gradients, pathway models,
      and turning-point models. Each is described and applied to the existing media
      effects literature. Recommendations for future research are discussed with regard
      to each model. In addition, we examine current developments in theorizing that
      stressors have sensitizing versus steeling effects and recent interest in
      biological and gene by environment interactions. We also discuss several of the
      cultural aspects that have supported the polarization and misunderstanding of the
      literature, and argue that applying risk and resilience models to the theories
      and data offers a more balanced way to understand the subtle effects of media
      violence on aggression within a multicausal perspective.

PMID- 24851352
TI  - Bringing a developmental perspective to early childhood and family
      interventionists: where to begin.
AB  - There is a pressing need to share advances in developmental science with the
      large, multidisciplinary professional workforce that serves vulnerable infants
      and toddlers and their families. Foundational knowledge and conceptual frameworks
      that integrate material regarding the contents and processes of early development
      and promotion of their use can assist interventionists and the families they
      serve. This chapter describes an approach that has been developed over the past
      10 years and summarizes key contents with sample practical applications. Topic
      areas include developmental theories, newborn capacities, a model for
      synthesizing information about early social competence (including self
      regulation, early relationships, social skills, and social cognition), and key
      current topics in developmental psychopathology. Brief considerations of
      diversity and stigma for work with young children and families are also included.

PMID- 24851353
TI  - Vocabulary development and intervention for English learners in the early grades.
AB  - The purpose of this chapter is to describe the vocabulary development and
      promising, evidence-based vocabulary interventions for English learners (ELs)
      from preschool through second grade. To achieve this purpose, we have taken six
      steps. First, we describe the elements of language development in the native
      language (L1) and a second language (L2) and how these elements relate to three
      phases of reading development (i.e., the prereading phase, the learning to read
      phase, and the reading to learn phase). We contend that in order for ELs to
      succeed in school, they need a strong language foundation prior to entering
      kindergarten. This language foundation needs to continue developing during the
      "learning to read" and "reading to learn" phases. Second, we describe the
      limitations of current practice in preschool for ELs related to vocabulary
      instruction and to family involvement to support children's language development.
      Third, we report curricular challenges faced by ELs in early elementary school,
      and we relate these challenges to the increase in reading and language demands
      outlined in the Common Core State Standards (CCSS). Specific language activities
      that can help meet some of the demands are provided in a table. Fourth, we
      synthesize the research on evidence-based vocabulary instruction and intervention
      and discuss implications for practice with ELs. Fifth, we describe two
      intervention projects under development that have the potential to improve EL
      vocabulary and language proficiency in the early grades. We conclude with a
      summary of the chapter and provide additional resources on the topic.

PMID- 24851354
TI  - [Pandemic influenza: entr'acte].

PMID- 24851355
TI  - [Levothyroxine and generics: current reflections].

PMID- 24851356
TI  - [Cancer: screening inconsistencies].

PMID- 24851357
TI  - [Borrelia-associated lymphocytoma cutis].

PMID- 24851358
TI  - [Kaposi sarcoma and HHV-8: a model of cutaneous cancer in immunosuppressed
      patients].
AB  - The virus HHV-8 will celebrate its twentieth birthday by the end of this year and
      its relationships with Kaposi sarcoma are not completely elucidated. HHV-8 is an
      enigmatic virus, with an inhomogeneous distribution, a salivary transmission
      while it is not an ubiquitous virus, at least in western countries. However, HHV
      8 has a unique genetic equipment rending is role in Kaposi sarcoma more than
      plausible. While the virus is necessary, it appears that it is not sufficient as
      the development of Kaposi sarcoma is frequently associated with immunosuppression
      whatever the cause (iatrogenic, viral, age-related). Kaposi sarcoma should be
      more considered as an opportunistic tumour than a viral-induced cancer and the
      best treatment for Kaposi sarcoma is immune restoration at least when it is
      possible.

PMID- 24851359
TI  - [Licit and illicit substance use during pregnancy].
AB  - Licit and illicit substance use during pregnancy is a major public health
      concern. Alcohol and substance (tobacco, cannabis, cocaine...) use prevalence
      during pregnancy remains under estimated. Some studies have reported the
      prevalence of alcohol or substance use in different countries worldwide but most
      of them were based on the mother's interview. Consumption of one or more
      psychoactive substances during pregnancy may have serious consequences on the
      pregnancy and on the child development. However, the type of consequences is
      still a matter of controversies. The reasons are diverse: different rating
      scales, potential interactions with environmental and genetic factors.
      Considering the negative consequences of drug use during pregnancy, preventive
      campaigns against the use of drugs during pregnancy are strongly recommended.

PMID- 24851360
TI  - [Post-traumatic pneumocephalus].

PMID- 24851361
TI  - [Recall or precision?].

PMID- 24851362
TI  - [Can we make the diagnosis of functional bowel disorders using only the clinical
      criteria of Rome III?].

PMID- 24851364
TI  - [Air pollution and acute coronary artery diseases incidence].

PMID- 24851363
TI  - [Risk of reactivation of hepatitis B in patients with the lymphoma HBsAg negative
      , anti-HBc positive treated with rituximab-CHOP].

PMID- 24851365
TI  - [ Occupational diseases--new risks and post-occupational follow-up].

PMID- 24851366
TI  - [How to establish the relationship between an occupational exposure and the
      occurrence of a disease?].
AB  - The establishment of causal relationship between a previous exposure and a
      disease is based on medical and scientific data. In France, three procedures
      operate for the recognition and the compensation of the diseases related to
      occupational exposure, to asbestos and to nuclear weapons tests. A suspicion of
      link is enough for the victim to initiate proceedings. The physician of each
      patient had to identify the exposure that could further the occurrence of their
      disease, to advise and to make the social allocations easier, and to certify the
      disease but not the link or exposure.

PMID- 24851367
TI  - [Economic burden of occupational diseases].

PMID- 24851368
TI  - [Consequences of recognition as an occupational disease by health insurance].

PMID- 24851369
TI  - [Psychosocial risks at work].
AB  - Psychosocial risks, characterized by their multiple causes in the workplace and
      consequences in terms of pathology, require interconnected medical and
      multidisciplinary management and care. Burn out syndrome is increasing and can
      possibly need to be declared as an occupational accident. Preventive actions must
      be favored considering the seriousness of some clinical settings.

PMID- 24851370
TI  - [News on occupational contact dermatitis].
AB  - Contact dermatitis--irritant contact dermatitis, allergic contact dermatitis and
      protein contact dermatitis--are the most common occupational skin diseases, most
      often localized to the hands. Contact urticaria is rarer The main occupational
      irritants are wet work, detergents and disinfectants, cutting oils, and solvents.
      The main occupational allergens are rubber additives, metals (chromium, nickel,
      cobalt), plastics (epoxy resins, acrylic), biocides and plants. Diagnosis is
      based on clinical examination, medical history and allergy testing. For a number
      of irritating or sensitizing agents, irritant or allergic dermatitis can be
      notified as occupational diseases. The two main prevention measures are reducing
      skin contact with irritants and complete avoidance of skin contact with offending
      allergens.

PMID- 24851371
TI  - [Work-related musculoskeletal disorders: priority to prevention and coordination
      of the interventions].
AB  - Upper-limb musculoskeletal disorders (UL-MSDs) are painful conditions related to
      the overuse of periarticular soft tissues. The main UL-MSDs are rotator cuff
      tendinopathy, epicondylalgia, carpal tunnel syndrome and non-specific pain UL
      MSDs are multifactorial disorders associated with individual and occupational
      (biomechanical, psychosocial and factors related to work organization) risk
      factors. Treatments are based on a global assessment of the clinical, social and
      occupational situations in order to identify cases of good prognosis and those,
      ess frequent, at high risk of prolonged work disability. The management of
      complex cases needs a close cooperation, with the agreement of the
      patient/worker, between the general practtioner and the occupational physician.
      One or more return to work visits are needed to help workers to keep their job.
      The prevention of UL-MSDs requires a global and integrated approach focusing on
      the reduction of the exposure to working constraints, early diagnosis and
      management and, if necessary, an intervention of stay at work. The new
      compensation procedures for UL-MSDs are described.

PMID- 24851372
TI  - [Idiopathic environmental intolerance: 2 disabling entities to recognize].
AB  - Idiopathic environmental intolerance is characterized by a variety of non
      specific symptoms involving several organs within the same individual, and
      attributed to the exposure to chemical odors (multiple chemical sensitivities) or
      to the exposure to electromagnetic fields (electromagnetic hypersensitivity).
      Symptoms occur following an exposure to agents generally regarded as harmless due
      to the low levels of exposure, and they do not answer to any definition of
      organic diseases. The lack of established etiology renders treatment difficult.
      It is important for practitioner to recognize such disorders and assess the
      social and professional impact so as to improve patients' quality of life.

PMID- 24851373
TI  - [Occupational diseases and night-shift work].
AB  - Shift and night work concern every year more and more workers, specifically
      women. Recent recommendations on good practice for the medical surveillance of
      shift and night workers have been edited in France. They confirmed that this kind
      of organisation, unavoidable in some economical sectors is associated with a
      significant higher risk of sleep and wake disorders, cardiovascular disorders,
      overweight and obesity, breath cancer. Specific surveillance of shift and night
      workers is recommended in occupational health.

PMID- 24851374
TI  - [Post-occupational medical follow-up: stakes, terms, obstacles].
AB  - The number of new cancers attributable to occupational exposure each year in
      France is estimated to be 20000, and about 25% of retired men have been
      occupationally exposed to asbestos, and 8% to wood dust. Since 1995, a post
      occupational medical follow-up exists for people, inactive, unemployed or (pre-)
      retired, who during their employment were exposed to some pneumoconiosis-causing
      agents and/or carcinogens occupational. This system is little known and
      underused. The obstacles to this follow-up are multiple and complex. The main is
      the lack of information of the various participants in the process (employees,
      former employees, physicians, employers) but the outlook is optimistic.
      Strengthening ties between generalist practitioners and occupational physicians
      are needed to improve the efficiency of post-occupational medical follow-up.

PMID- 24851375
TI  - [From EBM to centers of evidence].

PMID- 24851376
TI  - [Opioid substitution treatment and risk reduction].

PMID- 24851377
TI  - [The fight against the organ shortage].

PMID- 24851378
TI  - [Adult's heart failure].

PMID- 24851379
TI  - [Addiction to cannabis, cocaine, amphetamines, opiates, synthetic drugs].

PMID- 24851380
TI  - [Organ transplantation].

PMID- 24851381
TI  - [Bone fragility].

PMID- 24851382
TI  - [Private clinics and public hospitals in France: from complementarity to
      compromise].

PMID- 24851383
TI  - Dream job.

PMID- 24851384
TI  - Dentists, vaccines and disease detection.

PMID- 24851385
TI  - Not an arguable issue.

PMID- 24851386
TI  - Burdensome law.

PMID- 24851387
TI  - Invisalign: current guidelines for effective treatment.
AB  - Invisalign is an increasingly popular technique for aligning teeth and correcting
      malocclusions orthodontically. This article analyzes the current professional
      literature published on Invisalign and the benefits and risks of using the
      technique for both patients and doctors. The steady increase in the number of
      cases treated with Invisalign and where the technique is going in the future is
      investigated. Ten guidelines for Invisalign treatment and patient selection are
      given, along with case examples.

PMID- 24851388
TI  - Practice ownership in the age of big dental, big debt and mid-level providers.

PMID- 24851389
TI  - Elements in oral health programs.
AB  - Demographically, dental caries remains the single most common disease of
      childhood. Various campaigns have been carried out to promote and to improve the
      oral health of children. However, the prevalence of dental caries was still more
      than 50% in many communities. This article reviews different approaches used in
      dental health programs in industrialized and developing countries. To build a
      comprehensive oral health preventive program, three elements are essential. They
      are oral health education/instruction, primary prevention measures and secondary
      prevention measures.

PMID- 24851390
TI  - Interdisciplinary approach to oral rehabilitation of patient with amelogenesis
      imperfecta.
AB  - Amelogenesis imperfecta is a hereditary condition that affects the development of
      enamel, causing quantity, structural and compositional anomalies that involve all
      dentitions. Consequently, the effects can extend to both the primary and
      secondary dentitions. Patients with amelogenesis imperfecta may present with
      clinical difficulties, such as insufficient crown length, tooth sensitivity and
      orthodontic discrepancies, all of which can be resolved successfully with an
      interdisciplinary approach. This case report describes the interdisciplinary
      approach to the treatment of a 22-year-old patient with amelogenesis imperfecta.
      The proper alignment of anterior teeth and gingivo-cervical line was provided
      with orthodontic and periodontal treatments. All-ceramic crowns were placed on
      anterior, and metal-ceramic restorations were placed on posterior teeth to reduce
      sensitivity and improve esthetics with function. Improved esthetic appearance,
      reduced tooth sensitivity and the resolution of a potentially harmful
      psychosocial condition were achieved. Patient remained satisfied in the 12-month
      follow-up examination.

PMID- 24851391
TI  - Rigo-Fede disease: case report.
AB  - Riga-Fede disease results when an infant's instinctive tongue thrusting and
      raking motion over recently erupted primary mandibular incisors causes a
      traumatic ulceration of the tongue and/or mouth floor. The symptoms and
      therapeutic approach to the condition are highlighted in this case report.

PMID- 24851392
TI  - Use of oral healthcare and need to expand population that is served: a
      commentary.
AB  - General population demographics are undergoing dramatic changes. Long-term
      customary populations that provided the bulwark for successful dental practices
      are being replaced by the many minority populations. Despite these significant
      general population developments, the demographic profile of the dental profession
      has experienced (and, apparently, based on dental student populations, will
      continue to experience) limited changes. The economic strength of the profession
      may well be predicated upon its responses to these developments. The question
      remains, "Is the profession preparing for them?".

PMID- 24851393
TI  - Histologic findings within peri-implant soft tissue in failed implants secondary
      to excess cement: report of two cases and review of literature.
AB  - A link has been established between peri-implant disease and excess cement
      extrusion in cement-retained implant restorations. The histologic findings of two
      patients with failed implants secondary to residual excess cement are reported
      here. If excess cement is detected early and adequately removed, resolution can
      occur in the majority of situations. Simple recommendations are proposed, with
      the intention of preventing further implant failures from residual excess cement.

PMID- 24851394
TI  - Myositis ossificans of infraorbital musculature in uncontrolled diabetic.
AB  - Myositis ossificans traumatica is a form of dystrophic calcification that leads
      to heterotopic ossification of intramuscular connective tissue. It is rare in the
      orofacial region. A history of trauma, conventional radiography and computed
      tomography, along with histopathological examination, can be used effectively to
      diagnose this condition. We present a unique case of infected myositis ossificans
      traumatica in the infraorbital region in an uncontrolled diabetic.

PMID- 24851395
TI  - Oral osteosarcoma: a case report and analysis of previously reported cases.
AB  - Osteosarcoma is the most common malignancy of mesenchymal cells after
      hematopoietic neoplasms. Most originate within bones, but the occurrence of this
      malignancy in the jaw bones is rare. There is controversy about the
      characteristics of this tumor in the literature. The aim of this paper was to
      collect the previous reported data and provide a statistical analysis of them.
      Additionally, we have reported a case of mandibular osteosarcoma.

PMID- 24851396
TI  - Prescribe correctly: it's the law.

PMID- 24851398
TI  - Foreword. Chronobiology (time, clocks and calendars).

PMID- 24851397
TI  - UB researchers develop first evidence-based diagnostic criteria for TMD.

PMID- 24851399
TI  - Preface. Chronobiology.

PMID- 24851400
TI  - The circadian organization of the cardiovascular system in health and disease.
AB  - In normal conditions, the temporal organization of blood pressure (BP) is mainly
      controlled by neuroendocrine mechanisms. Above all, the monoaminergic systems
      (including variations in activity of the autonomous nervous system, and in
      secretion of biogenic amines) appear to integrate the major driving factors of
      temporal variability, but evidence is available also for a role of the
      hypothalamic-pituitary-adrenal, hypothalamic-pituitary-thyroid, opioid, renin
      angiotensin-aldosterone, and endothelial systems, as well as other vasoactive
      peptides. Many hormones with established actions on the cardiovascular system
      (arginine vasopressin, vasoactive intestinal peptide, melatonin, somatotropin,
      insulin, steroids, serotonin, CRF, ACTH, TRH, endogenous opioids, and
      prostaglandin E2) are also involved in sleep induction or arousal, which in turn
      affects BP regulation. Hence, physical, mental, and pathological stimuli which
      may drive activation or inhibition of these neuroendocrine effectors of
      biological rhythmicity, may also interfere with the temporal BP structure. On the
      other hand, the immediate adaptation of the exogenous components of BP rhythms to
      the demands of the environment are modulated by the circadian-time-dependent
      responsiveness of the biological oscillators and their neuroendocrine effectors.
      These notions may contribute to a better understanding of the pathophysiology and
      therapeutics of hypertension, myocardial ischemia and infarction, cardiac
      arrhythmias and all kind of acute cardiovascular accidents. For instance, the
      normal temporal balance between external stimuli and neurohumoral influences with
      endogenous rhythmicity is preserved in uncomplicated, essential hypertension,
      whereas it is frequently lost in complicated and secondary forms of hypertension
      where gross alterations are found in the circadian profile of BP. When all the
      gates of the critical physiologic functions are aligned at the same time, the
      susceptibility, and thus risk, of adverse events becomes extremely high, even in
      the presence of minor environmental stimuli that could be usually harmless, and
      circadian rhythms of cardiovascular events are observed. This implies that one
      cannot afford to miss what happens during day but also night. Moreover, the
      requirement for preventive and therapeutic interventions varies predictably
      during the 24 h, suggesting that the delivery of protective or preventive
      medications should be synchronized in time in proportion to need, as determined
      by established rhythmic patterns in cardiovascular function as well as risk, in a
      manner that will avert or minimize their undesired side effects.

PMID- 24851401
TI  - Chronodisruption, cell cycle checkpoints and DNA repair.
AB  - Chronodisruption, a disturbance in "natural" daily light/dark regulation, is
      possibly linked to disturbances in cell cycle homeostasis. The association and
      the synchronization between circadian rhythms and mitosis are not yet clear. The
      circadian oscillator is involved in the major cellular pathways of cell division.
      A molecular link between the circadian clock and the mammalian DNA damage
      checkpoints has been outlined. Analyses suggest an association between light
      disruption and obstruction of the cell cycle homeostasis. Disruption in the
      homeostatic control of the cell cycle has been associated with cancer and
      acceleration of malignant growth, possibly as a result of the interruption of DNA
      damage check-points. Studies further indicate that light signal during the dark
      phase affects the transcription level of a substantial number of genes that are
      associated with cell cycle progression, cell proliferation and tumorigenesis.
      Indeed, the International Agency for Research in Cancer categorized "shift work
      that involves circadian disruption" as possibly carcinogenic. In this review the
      current finding on light pollution and its potential influence on cell cycle
      check-points and DNA repair is presented.

PMID- 24851402
TI  - New methods to assess circadian clocks in humans.
AB  - Proper function of the circadian system seems crucial for human health. New
      advances in methods for assessment of the functional state of the human circadian
      system facilitate our understanding of the relationship between the disruption of
      the circadian system and various diseases. Based on the results of such studies,
      new directions for the diagnosis and treatment of diseases emerge. This
      communication aims to summarize current methods for evaluating the human
      circadian system in the laboratory as well as in field studies. The advantages
      and limitations of the current methods and various approaches used for both in
      vivo and in vitro assessment of the human circadian system are discussed.

PMID- 24851403
TI  - Photoperiodic regulation of seasonal reproduction in higher vertebrates.
AB  - Long-lived animals such as birds and mammals adapt readily to seasonal changes in
      their environment. They integrate environmental cues with their internal clocks
      to prepare and time seasonal physiological changes. This is reflected in several
      seasonal phenotypes, particularly in those linked with migration, hibernation,
      pelage growth, reproduction and molt. The two endocrine secretions that play key
      roles in regulating the seasonal physiology are melatonin and thyroid hormone.
      Whereas, melatonin is used as an endocrine index of day length (and consequently
      duration of night), the seasonal up- and down-regulation of thyroid hormone
      affects the physiology, perhaps by influencing different pathways. Both of these
      hormones are shown to act via a 'photoperiodic axis' constituted by the
      photoreceptors, hypothalamus and pituitary. Recent studies have revealed that the
      pars tuberalis that connects hypothalamus and pituitary, locally synthesizes the
      thyroid stimulating hormone (TSH) in response to light (birds) or melatonin
      (mammals). The levels of TSH regulate the DIO2 and DIO3 synthesis in the
      ependymal cells in hypothalamus, and in turn affect the release of gonadotropin
      releasing hormone. This review mainly focuses on the current understanding of the
      mechanisms of photoperiodic regulation of seasonal responses in the higher
      vertebrates.

PMID- 24851404
TI  - Twenty-four-hour pattern in French firemen of lag time response to out-of
      hospital cardiac arrest and work-related injury.
AB  - Circadian cognitive and physical rhythms plus 24 h patterns of accidents and work
      related injuries (WRI) have been verified in numerous studies. However, rarely,
      if ever, have 24 h temporal differences in both work performance and risk of WRI
      been assessed in the same group of workers. We explored in a homogenous group of
      French firemen (FM) 24 h patterns of both lag time (LT) response duration to
      emergency calls for medical help (ECFM) for life-threatening out-of-hospital
      cardiac arrests (OHCA), used as a non-specific index of work performance, and
      WRI. Our studies demonstrate rather high amplitude statistically significant 24 h
      patterns of the two variables. The LT response duration was twice as long -0500 h
      (slowest response) than -1600 h (fastest response). In the same group of FM, the
      actual number WRI/h was greatest -1600 h and lowest in the early morning hours.
      However, the 24 h pattern of the relative risk (RR) of WRIs, i.e., per clock hour
      number of WRI/(total number of responses to emergency calls x number of FM at
      risk per response), was very different, the RR being greatest -0200 h and lowest
      in the afternoon. The 24 h pattern in LT response duration to ECMH for OHCA and
      RR of WRI was strongly correlated (r = +0.85, P < 0.01), with the nocturnal
      trough (slowest response) in LT response duration coinciding with the nocturnal
      peak RR of WRI. These findings indicate the requirement for circadian rhythm
      based interventions to improve the nocturnal compromised work performance and
      elevated risk of WRI of shift-working FM.

PMID- 24851405
TI  - Melatonin: an internal signal for daily and seasonal timing.
AB  - Melatonin is secreted only during night, irrespective of the habitat of an
      organism and the site of its synthesis and secretion, and hence known as
      "darkness hormone". Elevated melatonin levels reflect the nighttime. In
      vertebrates, the main site of melatonin production is the pineal gland. Species
      in which melatonin is also secreted from sources other than the pineal, as in
      some birds, relative contributions of different melatonin producing tissues to
      the blood melatonin level can vary from species to species. Melatonin acts
      through its receptors, which are members of the G protein-coupled (GPCR)
      superfamily. Three melatonin receptors subtypes MT1 (mella), MT2 (mellb), and MT3
      (mellc) have been identified in different brain areas and other body organs of
      vertebrates. Melatonin synthesis and secretion are circadianly rhythmic. Changes
      and differences in specific features of melatonin signal can vary among species,
      and under a variety of natural environmental conditions. Two major physiological
      roles of melatonin are established in vertebrates. First, melatonin is involved
      in the circadian system regulated behavioural and physiological functions.
      Second, it is critical for the photoperiodic system. Besides, melatonin has been
      implicated in various ways both directly and indirectly to human health,
      including jet lag, sleep, immune system and cancer.

PMID- 24851406
TI  - Modulation of pineal activity during the 23rd sunspot cycle: melatonin rise
      during the ascending phase of the cycle is accompanied by an increase of the
      sympathetic tone.
AB  - In two groups of female CD-rats nocturnal urine (19-23 h, 23-3 h, 3-7 h) was
      collected at monthly intervals over 658 days (I: 1997-1999) and 494 days (II:
      1999-2000) coinciding with the ascending limb (1996-2000) of the 23rd sunspot
      cycle (1996-2008). The excretion of 6-sulfatoxymelatonin (aMT6s: I, II) was
      determined as well as the ratio of noradrenaline/adrenaline (NA/A: I) reflecting
      the activity of the sympathetic nervous system. AMT6s was higher in II than I (19
      7 h: +24%; P < 0.001; 23-3 h: +30% and 3-7 h: +17%, P < 0.001), and progressively
      increased (19-23 h) showing linear regressions (1: R = +0.737, P = 0.003; II: R =
      +0.633, 0.008) which correlated (I) with the Planetary Index (Ap: R = +0.598, P =
      0.020), an established estimate of geomagnetic disturbances due to solar
      activity. NA/A rose at all intervals (I: 46-143%) correlating with Ap (R = +0.554
      0.768; P = 0.0399-0.0013). These results indicate that melatonin secretion rises
      as solar activity increases during the ascending limb of a sunspot cycle
      accompanied by growing geomagnetic disturbances (Ap) which elevate the
      sympathetic tone and thus affect the pineal gland, initially stimulating the
      activity of arylalkylamine N-acetyltransferase and subsequently fostering the
      expression of N-acetylserotonin O-methyltransferase (rate-limiting enzyme for
      melatonin biosynthesis) if Ap increases further. The potential (patho)
      physiological significance of these findings is discussed and the need for a
      systematic continuation of such studies is emphasized.

PMID- 24851407
TI  - Light wavelength dependent circadian and seasonal responses in blackheaded
      bunting.
AB  - Animals in the wild are exposed to daily variations in sun light, viz. duration,
      intensity and spectrum. Photosensitive blackheaded buntings (Emberiza
      melanocephala) were exposed to photoperiods differing in the length of light
      period, wavelengths and intensity. The effects of such light changes were
      measured on locomotor activity rhythm as well as seasonal responses like
      development of migratory restlessness: Zugunruhe, body mass and gonadal growth.
      The results show that the buntings are differentially responsive to light
      wavelengths and intensities and are indicative of a phase-dependent action of
      light on the circadian photoperiodic system. These birds seem to use changes in
      the light variables of the solar environment to regulate their circadian and
      seasonal responses.

PMID- 24851408
TI  - Slow and fast orthodromic and antidromic variants in acute 9-h jet-lagged pygmy
      field mice.
AB  - Biological clocks help organism to adapt temporally to a variety of rhythmic
      environmental cues. Acute changes in the rhythmicity of entraining cues causes
      short- to long-term physiological distress in individuals, for example, those
      occurring during jet-lag after long-haul transmeridial flights, or shift work.
      Variations in the rate of re-entrainment to a 9 h advanced schedule (simulation
      of acute Jet-lag/shift work) in the Indian pygmy field mouse, Mus terricolor are
      reported. Wheel- and lab-acclimated adult male mice were entrained to a 12:12 h
      light:dark (LD) cycles, followed by a 9 h advance in the LD cycle. In response,
      these mice either advanced or delayed their activity onsets, with individual
      variation in the rate and direction. Rapid orthodromic (advancing) re-entrainers
      exhibited a coincidence of activity onsets with the new dark onset in < = 3 days,
      while gradually advancing re-entrainers took -9 days or more. Delayers
      (antidromic) also either re-entrained very rapidly (< = 2 days), or gradually (-9
      days). Acrophase measurement confirmed the direction of the transients, which did
      not depend on the free-running period. Such different patterns might determine
      the differential survival of individuals under the pressure of re-entrainment
      schedules seen in jet-lag and shift work.

PMID- 24851409
TI  - Daily variation in melatonin level, antioxidant activity and general immune
      response of peripheral blood mononuclear cells and lymphoid tissues of Indian
      goat Capra hircus during summer and winter.
AB  - Daily variation in circulatory melatonin level, during different seasons, has
      been reported to influence immune system and free-radical scavenging capacity in
      mammals, including human beings. Similar studies have not been carried out on
      small ruminant viz. goats that are susceptible to opportunistic infections,
      increased oxidative load and sickness during free-grazing activity and frequent
      exposure to agro-chemicals. Therefore, daily variation in immune status,
      antioxidant enzyme activity and its possible correlation with circulatory
      melatonin level during two different seasons, summer (long day) and winter (short
      day) were studied in the Indian goat, Capra hircus. The clinically important
      immune parameters, such as total leukocyte count, % lymphocyte count and %
      stimulation ratio of T-lymphocytes presented a day/night rhythm prominently in
      the winter. The oxidative load in terms of malonedialdehyde was always low during
      night while antioxidant enzymes superoxide dismutase, catalase and total
      antioxidant status were high during nighttime (1800 to 0600 hrs). Interestingly,
      the studied parameters were significantly higher during the winter in both the
      sexes. Rhythmometric analyses showed prominent rhythmicity in above parameters.
      The data presented strong positive correlation between high levels of nighttime
      melatonin levels and immune parameters during winter. It suggests that melatonin
      possesses immunoenhacing as well as antioxidative property during winter. This
      might be a necessity for maintenance of physiological harmony in goats to protect
      them from winter stress.

PMID- 24851410
TI  - Binding pattern of 125iodine thyroxine and tri-iodothyronine in skin and liver
      tissues of spotted munia, Lonchura punctulata: co-relation to seasonal cycles of
      breeding and molting.
AB  - Prevalent notion about thyroid hormones is that thyroxine (T4) is a mere
      precursor and physiological effects of thyroid hormones are elicited by tri
      iodothyronine (T3) after mono-deiodination of T4. Earlier studies on feather
      regeneration and molt done on spotted munia L. punctulata suggest that T4 (mono
      deiodination suppressed by iopanoic acid and thyroidectomized birds) is more
      effective than T3 in inducing feather regeneration. The binding pattern of 125I
      labeled T4 and T3 has been investigated in the nuclei prepared from skin and
      liver tissues (samples obtained during different months) of spotted munia using
      scatchard plot analysis. The results show that binding capacity (B(max)--pmole/80
      microgm DNA) of 125I-T3 to nuclei of skin was significantly higher in November as
      compared to April and June, whereas the binding affinity (Kd-10(-9)M(-1)) was
      significantly lower in November as compared to April and June. During November,
      B(max) for binding of T3 and T4 did not vary in liver and skin nuclei but Kd
      varied significantly. Binding capacity of 125I- T3 to skin and liver did not vary
      but binding affinity of 125I- T4 to skin was approximately 7 times higher than
      that of liver. The results suggest that T4 does show a variation in binding
      pattern that co-relates to the molting pattern of spotted munia. These variations
      might play important role in different physiological phenomenon in this tropical
      bird. The experiments do point towards the possibility of independent role of T4
      as a hormone, however, further experiments need to be done to ascertain the role
      of T4 in this model and work out the exact molecular mechanism of action.

PMID- 24851411
TI  - Internal coincidence of serotonergic and dopaminergic oscillations modulates
      photo sexual responses of Japanese quail, Coturnix coturnix japonica.
AB  - Specific temporal phase relation of neural oscillations appears to be the
      regulator of gonadal development in many seasonally breeding species. To find out
      the specific phase angle of two neural oscillations that triggers gonado
      inhibitory or gonado-stimulatory response, and to test the internal coincidence
      model, sexually immature male Japanese quail were administered with the serotonin
      precursor, 5-hydroxytryptophan and the dopamine precursor, L
      dihydroxyphenylalanine at hourly intervals of 6, 7, 8, 9, 10, 11 and 12 h (5
      mg/100 g body weight/day for 12 days under continuous condition of light, LL).
      Thereafter all the groups were shifted to long photoperiod (LD16:8). During post
      treatment period, in general, a significant suppression of gonadal activity was
      seen in the 7 h and 8 h quail and an increase in the 11 h and 12 h quail compared
      to the control and these effects were maintained until 105 days post treatment
      when the study was terminated. These findings suggest that, in addition to the
      effects of photoperiod, the gonadal development of Japanese quail may be also
      modulated by internal coincidence of serotonergic and dopaminergic oscillations
      (induced by the administration of their precursor drugs) and the gonadal response
      varies depending on the time interval between the administrations of two drugs on
      a circadian basis. These results also demonstrate inversion of gonadal response
      from 7/8 h (suppressive) to 11/12 h (stimulatory) phase relation of the two
      oscillations and suggest that similar to photoperiodic time measurement, Japanese
      quail may also detect changes in the phase angle of circadian oscillations to
      modulate its gonadal activity.

PMID- 24851412
TI  - Participation of endogenous circadian rhythm in photoperiodic time measurement
      during ovarian responses of the subtropical tree sparrow, Passer montanus.
AB  - Resonance experiment was employed to investigate the mechanism of photoperiodic
      time measurement during initiation of ovarian growth and functions in the
      subtropical population of female tree sparrow (Passer montanus) at Shillong
      (Latitude 25 degrees 34 'N, Longitude 91 degrees 53 'E). Photosensitive birds
      were subjected to various resonance light dark cycles of different durations such
      as: 12-(6L:6D), 24-(6L:18D), 36-(6L:30D), 48-(6L:42D), 60-(6L:54D) and 72
      (6L:66D) h along with a control group under long days (14L:10D) for 35 days.
      Birds, exposed to long days, exhibited ovarian growth confirming their
      photosensitivity at the beginning of the experiment. The birds experiencing
      resonance light/dark cycles of 12, 36 and 60 h responded well while those exposed
      to 24, 48 and 72 h cycles did not. Serum levels of estradiol-17beta ran almost
      parallel to changes in the follicular size. Further, histomorphometric analyses
      of ovaries of the birds subjected to various resonance light dark cycles revealed
      distinct correlation with the ovarian growth and the serum levels of estradiol
      17beta. No significant change in body weight was observed in the birds under any
      of the light regimes. The results are in agreement with the avian external
      coincidence model of photoperiodic time measurement and indicate that an
      endogenous circadian rhythm is involved during the initiation of the gonadal
      growth and functions in the female tree sparrow.

PMID- 24851413
TI  - Daily and seasonal activity patterns in blackheaded munia.
AB  - To test the circadian clock characteristics, activity behaviour of male
      blackheaded munia was recorded. Two experiments were performed. In experiment 1A,
      activity of munia was recorded under long days, LD (14L: 10D); and short days, SD
      (10L: 14D). Locomotor activity of two groups of munia exposed to equinox (12L:
      12D) daylength followed by transfer of one group each to continuous dimlight (DD)
      and continuous bright light (LL) was recorded in experiment 1B. Experiment 2
      aimed to describe seasonal trend in daily pattern of activity/rest cycle under
      natural illumination conditions (NDL). Hourly activity during daytime was more
      under SD than under LD. Munia did not exhibit bimodality in daily activity
      pattern; activity during morning, M (2h) was more than evening, E. A free-running
      activity rhythm was recorded in munia under DD; the same was arrhythmic under LL.
      The seasonal pattern in daily activity profiles under NDL corresponds to the
      seasonal changes in daylength. Daylength regulates daily and seasonal activity
      patterns in blackheaded munia.

PMID- 24851414
TI  - Effects of light intensity on circadian activity behaviour in the Indian
      weaverbird (Ploceus philippinus).
AB  - Circadian (locomotor activity/perching) behaviour of the weaverbird (Ploceus
      philippinus) under different light intensities was studied. Six groups of birds
      were subjected to 12L:12D (L = 1000 and 10 lux and D = 0.3 lux) for two weeks,
      and thereafter released into constant dim illumination (LL(dim) = 0.3 lux). After
      two weeks of LL(dim), birds were given a 2 h light pulse of 1000 lux at circadian
      time (CT) 12, 17 and 20, and exposure of LL(dim) was continued for another two
      weeks and the activity pattern was monitored. As expected, all birds were
      entrained under 12L:12D showing dense-activity in the group that was placed under
      light phase of 1000 lux. Under LL(dim) birds exhibited circadian activity rhythms
      with periods longer or shorter than 24 h. Light pulse at CT 12 caused small delay
      shift in the activity phase, but a larger delay in phase shift occurred when the
      pulse was given at CT 17. A pulse at CT 20 caused small advanced phase shift.
      Thus, photoperiodic weaverbird appears to show circadian system regulated
      behaviour as seen by activity-rest pattern under programmed light cycles.

PMID- 24851415
TI  - Daily behaviour can differ between colour morphs of the same species: a study on
      circadian activity behaviour of grey and pied zebra finches.
AB  - To investigate if the plumage colour mutation relates to circadian activity
      behaviour in the zebra finch, Taeniopygia guttata, wild type grey and pied mutant
      males were sequentially subjected for three weeks each to 12 h light:12 h
      darkness (12L:12D) and constant dim light (LL(dim)) condition. During the first 3
      h of the 12 h day, pied finches were significantly greater active than grey
      finches. Also, as compared to grey, pied finches had longer activity duration in
      the day, with early activity onsets and late activity offsets. This was changed
      under free-running condition (LL(dim)), when the activity later in the subjective
      day (clock hour 9 and 11) was significantly greater in grey than in pied
      finches.Two colour morphs differed in daily activity profile, but not in the
      total daily activity or circadian rhythm period. Results suggest that greyzebra
      finches represent late chronotype, and could perhaps be better adapted to a
      seemingly stressful environment, such as low intensity LL(dim) in the present
      study.

PMID- 24851416
TI  - Photoperiodic effects on activity behaviour in the spiny eel (Macrognathus
      pancalus).
AB  - The study focused on the characteristics of circadian locomotor activity in the
      spiny eel, M. pancalus, kept under different photoperiodic conditions. Two
      experiments were conducted. Experiment 1 tested the light intensity dependent
      effect on circadian rhythmicity of the locomotor activity in spiny eel. Three
      groups of fish were entrained to 12L:12D conditions for 10 days. Thereafter, they
      were released to constant conditions for 15 days as indicated below: group 1-DD
      (0 lux), group 2- LL(dim) (-1 lux) and group 3-LL(bright) (-500 lux). The
      locomotor activity of the fish, housed singly in an aquarium, was recorded
      continuously with infrared sensors connected to a computer. More than 90%
      activity of the eels was confined to the dark hours suggesting nocturnal habit.
      Under constant conditions, the activity in 7/9 fish in group 1, 4/8 in group 2
      and 3/8 in group 3, started free running with a mean circadian period of 24.48 +/
      0.17 h, 23.21 +/- 0.47 h and 25.54 +/- 1.13 h in respective groups. Remaining
      fish in each group became arrhythmic. This suggests that spiny eel can be
      synchronised to LD cycle and under constant conditions they free run with a
      circadian period. However, their activity under LL is light intensity dependent;
      higher the intensity, more disruption in circadian locomotor activity. Experiment
      2 was conducted to study the effect of decreasing night length (increasing
      photoperiod) on circadian locomotor activity. The fish were sequentially exposed
      to 16D (8L:16D), 12D (12L:12D), 8D (16L:8D), 4D (20L:4D) and 2D (22L:2D) for 10
      days in each condition, thereafter, they were released in constant dark (DD=
      0lux). The results showed that the duration of night length affects both, the
      amplitude and duration of locomotor activity. It can be concluded that the spiny
      eels are nocturnal and that their locomotor activity is under the circadian
      control and may be influenced by the photoperiod.

PMID- 24851417
TI  - Aromatase activity in brain and ovary: seasonal variations correlated with
      circannual gonadal cycle in the catfish, Heteropneustes fossilis.
AB  - Seasonal variations in the aromatase activity in H. fossilis estimated by a
      microassay were correlated with the sex steroids, vitellogenin in and ovarian
      weight during circannual reproductive cycle. In the female catfish, aromatase
      activity was detectable in the hypothalamus throughout the year whereas in ovary
      only during active vitellogenesis. In the catfish, hypothalamic aromatase levels
      increased two times during annual gonadal cycle, once in a fully gravid fish and
      then in a reproductively quiescent fish. On the other hand, increase in the
      ovarian aromatase activity was observed only during vitellogenesis, which showed
      a direct correlation with plasma levels of sex steroids. Further, plasma levels
      of testosterone and estradiol suggested a precursor-product relationship. At the
      completion of vitellogenesis, ovarian aromatase activity declined sharply
      resulting in elevation of plasma testosterone levels, which in turn could be
      utilized as substrate by the hypothalamic aromatase whose activity was the
      highest in the postvitellogenic catfish. At least two isoforms of gene, cyp19a
      and cyp19b, coding for aromatase in ovary and brain respectively were expressed
      in the catfish. Aromatase activity was more concentrated in those areas of
      catfish brain, which have been implicated in the control of reproduction.

PMID- 24851418
TI  - Season-dependent effect of thermopulse on gonadal recrudescence in the female
      catfish, Clarias batrachus.
AB  - In the present study, the female Clarias batrachus, held under long photoperiod
      (13L:11D), were exposed to high water temperature either constantly (24 h) and/or
      in form of thermopulse of 6 h and 12 h durations, separately, at different times
      of the day/night cycle for six weeks during the early post-spawning and late post
      spawning phases of its reproductive cycle. The effects of high water temperature
      (30 +/- 1 degrees C) on gonadosomatic index (GSI), plasma levels of testosterone
      (T) and oestradiol-17beta (E2) were observed. During the late post-spawning
      phase, thermopulse of 12 h duration given in the morning hour increased all the
      studied parameters most effectively as compared to that given at evening hour of
      the day/night cycle or even in comparison to the fish exposed to constant high
      temperature. Thermopulse of 6 h duration given in the morning or noon also raised
      these parameters compared to the controls, but the magnitudes of stimulation were
      moderate. However, exposures of the catfish to such photothermal regimes during
      the early post-spawning phase completely failed to bring any change in the
      studied parameters. These findings, thus, clearly indicate that treatment with
      high temperature under long photoperiod may stimulate gonadal activity in C.
      batrachus, provided given at appropriate season of the year. A diurnal basis of
      response to high temperature and the existence of a rigid gonado-refractory phase
      (perhaps just after the spawning) are also evident in the reproductive cycle of
      C. batrachus.

PMID- 24851419
TI  - Blood pressure variability and pedigree analysis of nocturnal SBP dipping in
      Kumbas from rural Chhattisgarh, India.
AB  - Family is the smallest unit of people to share most of the lifestyle,
      environmental and genetic factors. They are likely to have similarity in many
      physiological and behavioural aspects. Therefore, we designed a protocol to test
      the effect of large rural Indian families living together (Kumbas), on blood
      pressure variability. We also investigated the hypothesis that 'nocturnal
      dipping' in systolic blood pressure (SBP) is not heritable. Members of two
      families (1 and 2) consisting of 3-4 generations willingly participated in the
      study. Both families (natives of Chhattisgarh) belong to reasonably peaceful
      rural area and are financially stable. Farming is the main occupation of the
      members of both families. Few members of the families had jobs or small business.
      The null hypothesis regarding heritability of nocturnal dipping trait was
      accepted based on data emanating from either of the studied families. Hourly
      averaged values depicted less variation in males and females of family 1 from
      midnight to early morning at around 06:00, as compared to that in males and
      females of family 2. The 24 h averages of BP in family 2 were significantly
      higher as compared to that in family 1. Further, in family 2 the peaks of SBP,
      diastolic blood pressure (DBP) and mean arterial pressure (MAP) occurred
      significantly earlier as compared to that in family 1. The peak spread of SBP,
      DBP, heart rate (HR), MAP and pulse pressure (PP) among the members of family 1
      was narrower than that for the members of family 2. Arbitrary cut-off values for
      classification of dipping, small sample size, and age dependency of nocturnal
      dipping might have marred outcome of the pedigree analysis of nocturnal dipping
      trait in this study. We have a hunch that the family shares typical temporal ups
      and downs in 24 h BP and HR. The above hypothesis needs confirmation based on
      studies with large data set involving subjective and objective assessment of the
      effects of psychosocial factors on BP and HR variability.

PMID- 24851420
TI  - Effect of hospitalization on rest-activity rhythm and quality of life of cancer
      patients.
AB  - Rest-activity rhythm and quality of life (QoL) in three cohorts, namely (1)
      cancer in-patients, (2) out-patients, and (3) control subjects were studied. The
      patients of the former two groups were chosen randomly from the Regional Cancer
      Center, Raipur, India. All patients received chemotherapy for 3-4 consecutive
      days. The in-patients remained hospitalized for the entire period of chemotherapy
      plus one day post treatment. The out-patients, unlike the in-patients, went to
      their homes daily after treatment. Rest-activity rhythm of the patients was
      monitored using Actical. Quality of life (QoL) and psychological status of
      patients were assessed using EORTC QLQ-C30 and Hospital Anxiety & Depression
      Scale, respectively. Each subject exhibited significant circadian rhythm in rest
      activity. The average values for Mesor, amplitude, peak activity, autocorrelation
      coefficient and dichotomy index of all three groups varied significantly between
      one group to the other in the following order: in-patient < out-patient <
      control. Further, quality of life, measured from responses on functional and
      symptom scales, was better off in cancer out-patients compared to the in
      patients. It is concluded that hospitalization alters rest-activity rhythm
      parameters markedly and deteriorates QoL in cancer patients. Nevertheless,
      further extensive investigation is desirable to support the above speculation and
      to ascertain if hospitalization produces similar effects on patients suffering
      from diseases other than cancer.

PMID- 24851421
TI  - Short-duration judgment in young Indian subjects under 30 h constant wakefulness.
AB  - The present study aimed to investigate probability of a possible endogenous
      circadian rhythm in human cognitive attribute to estimate short intervals.
      Apparently healthy young males and females were selected for our study. Eight
      subjects prospectively produced the short-time intervals 10 s and 60 s at 2
      hourly intervals in 30 h constant routine (CR) study conducted in spring (CR-1).
      The study was repeated again in autumn (CR-2) in the remaining eight subjects.
      The established circadian markers, namely serum cortisol, salivary melatonin
      levels and tympanic temperature were also measured either in CR-1 or CR-2. Oral
      temperature was measured simultaneously. Circadian rhythms were validated in
      serum cortisol, salivary melatonin, oral, and tympanic temperatures. Circadian
      rhythm in 60 s estimates was observed in a few subjects and in all males at group
      level in CR-1. The cognitive attribute to perceive short intervals vary as
      function of season. The results provide evidence in support of interaction among
      the interval, circadian and circannual timing systems in human.

PMID- 24851422
TI  - Relationship of chronotype to sleep pattern in a cohort of college students
      during work days and vacation days.
AB  - To study whether the chronotype is linked with the sleep characteristics among
      college going students assessed during college days and vacation days, adult
      female students at undergraduate level were asked to answer the Hindi/English
      version of the Munich Chronotype Questionnaire (MCTQ), fill a sleep log, and
      drinking and feeding logs for three weeks covering college and vacation days.
      Based on chronotype categorization as morning type, intermediate type and evening
      type, sleep onset and offset times, sleep duration and mid-sleep times for each
      group were compared, separately for college and vacation days. Results indicate
      that the sleep duration of the morning types was significantly longer than the
      evening types, both, during college and vacation days. Similarly, the sleep onset
      and sleep offset times were significantly earlier in the morning types than the
      evening type students. During the vacation days, the individuals exhibited longer
      sleep duration with delayed mid-sleep times. Further there was no significant
      difference among the chronotypes regarding their feeding and drinking frequency
      per cent during the college and the vacation days. It is suggested that the
      students should be made aware of their chronotype, so that they can utilize their
      time optimally, and develop a schedule more suitable to their natural needs.

PMID- 24851423
TI  - [Lump in the throat - problems breathing].

PMID- 24851424
TI  - [Coffee - a stimulant for the liver].

PMID- 24851425
TI  - [No cell phone, computer or tablet before going to bed!].

PMID- 24851426
TI  - [Preparation for retirement. Physician 60-years-old - when will you stop?].

PMID- 24851427
TI  - [E-card and telematics. Safe and efficient in the digital network of the health
      care system].

PMID- 24851428
TI  - [Euthyroid struma with a thyroid nodule. Is the combination of L-thyroxine and
      iodine effective here?].

PMID- 24851429
TI  - [Evaluation of chronic diarrhea. No shotgun diagnosis!].

PMID- 24851430
TI  - [Acute mesenteric ischemia emergency. The pitfalls of a false relief].

PMID- 24851431
TI  - [Fever and epigastric pain. It could be a liver abscess].

PMID- 24851432
TI  - [Vaccinations in adults. Fill in the gaps!].

PMID- 24851433
TI  - [Naturopathy consultation. Light and plants for the psyche].

PMID- 24851434
TI  - [Tumor markers, mammography and colon cancer screening. Prevention in oncology -
      what makes sense, what does not?].

PMID- 24851435
TI  - [Looking for the cause. Would iron deficiency anemia cause sudden deafness?].

PMID- 24851436
TI  - [Early intervention against chronification. In pain medicine do not hold back, be
      assertive (interview by Dr. Christine Starostzik)].

PMID- 24851437
TI  - [In retirement pills often lie untouched].

PMID- 24851438
TI  - [Psychiatric illnesses have increased worldwide].

PMID- 24851439
TI  - [High risk of relapse in opiate intoxication].

PMID- 24851440
TI  - [In atrial fibrillation is anticoagulation too often omitted?].

PMID- 24851441
TI  - [With sleep apnea into social isolation].

PMID- 24851442
TI  - [Bothered by menopausal symptoms--what to recommend your patient?].

PMID- 24851443
TI  - [Hormone therapy during peri- and postmenopause].

PMID- 24851444
TI  - [Phytotherapy in menopausal symptoms].

PMID- 24851445
TI  - [Atopic eczema].

PMID- 24851446
TI  - [Unintended weight loss].

PMID- 24851447
TI  - [Mid-foot fractures of the chopart and lisfranc joint line].

PMID- 24851448
TI  - [Obesity and diabetes in young adults].

PMID- 24851449
TI  - [Which antidepressant for what patients? St. John's wort: broad application - new
      mechanism of action].

PMID- 24851450
TI  - Why implementing the ACA has been harder than we thought.
AB  - With March 2014 past and the 2014 enrollment period having ended with it, the
      first major implementation phase of the Affordable Care Act (ACA) also has ended.
      It is too soon to know how many have enrolled, how many have paid their first
      month premiums, how many will continue to pay their premiums throughout the year,
      and how many were previously uninsured, or any details on other key issues that
      have been raised. But it is not too soon for a general assessment of this initial
      phase of the ACA roll-out, especially now that we have passed the four-year
      anniversary of the bill's signing.

PMID- 24851451
TI  - Tying supply chain costs to patient care.
AB  - In September 2014, the FDA will establish a unique device identification (UDI)
      system to aid hospitals in better tracking and managing medical devices and
      analyzing their effectiveness. When these identifiers become part of patient
      medical records, the UDI system will provide a much-needed link between supply
      cost and patient outcomes. Hospitals should invest in technology and processes
      that can enable them to trace supply usage patterns directly to patients and
      analyze how these usage patterns affect cost and quality.

PMID- 24851452
TI  - 5 strategies for lessening the self-insurance impact of the ACA.
AB  - Many healthcare organizations use self-insurance programs to control professional
      liability and workers' compensation exposures, such as self-insured retention, a
      large deductible program, a trust fund, or a captive. The impact of the
      Affordable Care Act on self-insurance programs may take years to determine.
      Communication among all areas involved in the self-insurance program and the
      evaluation of different cost perspectives will be key to keeping the self
      insurance program financially healthy. Empowering actuaries to create different
      scenarios also will help leaders stay on top of the issue.

PMID- 24851453
TI  - Atul Gawande understanding the forces driving healthcare change.

PMID- 24851454
TI  - Ripple effects of reform on capital financing.
AB  - Healthcare leaders should inventory and quantify the capital initiatives deemed
      critical for success under changing business models. Key considerations in
      planning such initiatives are opportunity costs and potential impact on
      productivity. Senior leaders also should create rolling five-year estimates of
      expenditures in addition to a one-year budget. Approaches to paying for such
      initiatives include borrowing from cash reserves, partnering to share cash and
      other resources, and developing new revenue sources derived from the initiatives
      themselves.

PMID- 24851455
TI  - Building blocks for organizational change.
AB  - To understand the types of organizational change that will best help them meet
      strategic goals, hospitals and health systems are: Projecting their quality and
      savings goals for the coming years and weighing their ability to meet them.
      Looking for partner organizations that share their culture, goals, and
      capabilities. Assessing the types of organizational arrangements that will
      provide the desired benefits. Determining the key components needed to make the
      arrangement fit their goals and culture.

PMID- 24851456
TI  - Determining your organization's 'risk capability'.
AB  - An assessment of a provider's level of risk capability should focus on three key
      elements: Business intelligence, including sophisticated analytical models that
      can offer insight into the expected cost and quality of care for a given
      population. Clinical enterprise maturity, marked by the ability to improve health
      outcomes and to manage utilization and costs to drive change. Revenue
      transformation, emphasizing the need for a revenue cycle platform that allows for
      risk acceptance and management and that provides incentives for performance
      against defined objectives.

PMID- 24851457
TI  - Improving price transparency: an overview of the HFMA price transparency task
      force report.
AB  - Over the past year, it has become abundantly clear that many Americans are
      concerned about the cost of their health care and want to be better healthcare
      consumers. But some have been frustrated by the lack of readily accessible
      information on healthcare prices.

PMID- 24851458
TI  - Time to replace adjusted discharges.
AB  - With inpatient revenue averaging less than 50 percent of total operating revenue
      for hospitals and bundled payments becoming the norm, Equivalent Discharges is a
      simple, alternative metric that offers superior predictive power of hospital
      volume. Equivalent Discharges are not subject to the same measurement flaws as
      adjusted discharges or adjusted patient days. The new metric also explains cost
      variation in situations where there is a more complex case mix.

PMID- 24851459
TI  - Managing chronic conditions: economic analysis can help mitigate costs of
      diabetic ulcers.
AB  - Hospital finance leaders should perform economic analyses of emerging treatments
      for chronic conditions that could provide cost-effective alternatives to
      generally accepted standards of care. One such treatment for diabetic foot ulcers
      (DFUs) is noncontact low-frequency ultrasound, which has been shown to reduce
      both costs and healing times associated with these conditions. By reviewing
      results of clinical trials to understand the costs and treatment considerations
      for DFUs and other chronic conditions, finance leaders can engage in informed
      conversations with physicians on how best to manage costs.

PMID- 24851460
TI  - Analyzing financial performance in the new world.
AB  - Over the past several years, health care has seen the beginnings of a significant
      transformation in the nature of analytics. This transformation is being driven by
      the advent of a new world in which providers hold increased accountability for
      the efficiency, quality, and safety of the care that their organizations provide-
      and it is occurring across several dimensions.

PMID- 24851461
TI  - Competitive collaborators.

PMID- 24851462
TI  - The fiscal and political realities of SGR reform.

PMID- 24851463
TI  - Risk and return in the post-crisis world.
AB  - In the wake of the global financial crisis, the actions of leading central banks
      appear to have modified some of the long-established relationships between risk
      and return. But those principles may reassert themselves in the coming years as
      the financial environment returns to longstanding earlier patterns.

PMID- 24851464
TI  - Opportunity knocks.

PMID- 24851465
TI  - Palliative and end-of-life care in South Dakota.
AB  - BACKGROUND: Geographical disparities play a significant role in palliative and
      end-of-life care access. This study assessed availability of palliative and end
      of life (hospice) care in South Dakota. METHODS: Grounded in a conceptual model
      of advance care planning, this assessment explored whether South Dakota health
      care facilities had contact persons for palliative care, hospice services, and
      advance directives; health care providers with specialized training in palliative
      and hospice care; and a process for advance directives and advance care planning.
      Trained research assistants conducted a brief telephone survey. RESULTS: Of 668
      health care eligible facilities, 455 completed the survey for a response rate of
      68 percent (455 out of 668). Over one-half of facilities had no specific contact
      person for palliative care, hospice services and advance directives. Nursing
      homes reported the highest percentage of contacts for palliative care, hospice
      services and advance directives. Despite a lack of a specific contact person,
      nearly 75 percent of facilities reported having a process in place for addressing
      advance directives with patients; slightly over one-half (53 percent) reported
      having a process in place for advance care planning. Of participating facilities,
      80 percent had no staff members with palliative care training, and 73 percent
      identified lack of staff members with end-of-life care training. Palliative care
      training was most commonly reported among hospice/home health facilities (45
      percent). CONCLUSIONS: The results of this study demonstrate a clear need for a
      health care and allied health care workforce with specialized training in
      palliative and end-of-life care.

PMID- 24851466
TI  - Acute cerebrovascular accident in an 18-year-old male with von Willebrand
      disease.
AB  - Compared to the older populations, stroke is an infrequent occurrence in
      children, adolescents, and young adults. Furthermore, individuals who have
      hypocoagulability disorders, such as von Willebrand disease (vWD), appear to
      possess a degree of protection against thrombotic events. Here, we describe an 18
      year-old male with a history of vWD who presented to the emergency department
      with left sided hemiparesis that occurred shortly after being placed in a
      headlock while wrestling. MRI revealed a right paramedian pontine stroke. The
      relationship between vWD and stroke is discussed as well as the role of neck
      trauma in vertebral artery injury. While vWD does appear to decrease the
      incidence of thrombotic events, such patients are still at risk, especially in
      the context of common inciting events such as neck trauma.

PMID- 24851467
TI  - Death certification: a primer. Part I--an introduction to the death certificate.
AB  - Unlike the medical record, the death certificate is a public legal document that
      deserves the certifier's best intellectual effort to complete. The death
      certificate serves a variety of purposes, to include: A. Legal proof of death,
      usually necessary for a family to receive social security, health insurance, and
      other death benefits. B. A closure statement to the family from the physician
      documenting his or her final diagnosis. C. A family heirloom document that
      preserves a family history of causes of death (which may be invaluable in
      documenting hereditary diseases within a family). D. The death certificate is the
      backbone of national death statistics. Incorrect data from death certificates
      translates into incorrect state and national death rates for all causes. Cause of
      death assessment is inherently inaccurate (autopsy studies suggest that at least
      10 percent of deaths have major unrecognized underlying disease processes that
      would have altered therapy had they been known). Even correct diagnostic
      assessments, however, can be lost to the system if they are improperly entered on
      to the death certificate.

PMID- 24851468
TI  - Norepinephrine vs. dopamine: new recommendations for initial vasopressor
      selection in septic shock.

PMID- 24851469
TI  - SDSMA Center for Physician Resources Practice of Medicine Series--Reporting
      obligations in the event of a data breach.

PMID- 24851470
TI  - Quality focus: Electronically specified clinical quality measures.

PMID- 24851471
TI  - DAKOTACARE's integrated medical and pharmacy management: enhancing value.

PMID- 24851472
TI  - Eclectic child welfare approaches to working with children, youth, and families.

PMID- 24851473
TI  - Pre-placement risk and longitudinal cognitive development for children adopted
      from foster care.
AB  - This study examined the trajectory of cognitive development over the first five
      years of adoptive placement among children adopted from foster care and how pre
      adoption risk factors relate to this development. Overall, children's cognitive
      scores increased significantly, with the most rapid improvement occurring in the
      first year post-placement. By five years post-placement, children's mean
      cognitive and achievement scores were in the average range. Adoption is a
      positive intervention for children's cognitive development.

PMID- 24851474
TI  - Challenges to recruit and retain American Indian and Alaskan Natives into social
      work programs: the impact on the child welfare workforce.
AB  - There is a shortage of professionally trained American Indian/Alaskan Native
      (AI/AN) social workers available to provide services including child welfare
      services to tribal communities. This study used a mixed-model survey design to
      examine the perceptions of 47 AI/AN BSW and MSW students enrolled in social work
      programs across the to determine the challenges associated with recruitment and
      retention. The findings are supported in the literature. Findings indicate that
      social work academic programs have not made substantial gains in the recruitment
      and retention of AI/AN students over several decades. Students identified the
      following seven major barriers to successful recruitment and retention: (1) a
      lack of AI/AN professors; (2) a shortage of field placement agencies that serve
      AI/AN clients; (3) conflicts between students' academic obligations and
      responsibilities to their families and tribal communities; (4) students' feelings
      of cultural isolation; (5) the need for AI/AN role models and mentors; (6) a lack
      of understanding by universities of cultural customs and traditional values; and
      (7) racism. Implications for policy and practice are offered.

PMID- 24851475
TI  - Acknowledging the past while looking to the future: conceptualizing indigenous
      child trauma.
AB  - Trauma affects children from all ethnicities, nationalities and socioeconomic
      backgrounds. However, indigenous children may experience trauma differently than
      their majority population peers due to traumatic histories of colonization and
      marginalization. This article reports on an exploratory qualitative study of how
      service providers in Western Montana and Northern Norway conceptualize Native
      American and Sami children's experiences of trauma today. Findings reveal that
      participants relate current trauma experiences of indigenous youth to historical
      and intergenerational traumas.

PMID- 24851476
TI  - Peer-centered practice: a theoretical framework for intervention with young
      people in and from care.
AB  - This paper puts forward a conceptual framework for engaging peers as central to
      transitional services for care-leavers. The situation of youth exiting care is
      examined and an evidence-informed approach to supporting care-leavers is
      presented. Exploring the social networks of youth leaving care provides a
      mechanism for both supporting the maintenance of ties and fostering the
      development of weak tie connections that facilitate opportunities for social
      mobility.

PMID- 24851477
TI  - Wisconsin's Community Response Program for families that have been reported for
      child maltreatment.
AB  - In 2006, the Wisconsin Children's Trust Fund launched a pilot initiative called
      "Community Response," a program targeted to families reported for maltreatment
      but not served by child protective services due to insufficient child safety
      concerns. This article presents general information on the program, including the
      variation in models used by sites across the state, information on the families
      that were served by the program, and lessons learned from the experience that may
      guide practical decisions around the implementation of similar models elsewhere.

PMID- 24851479
TI  - Embracing diversity.

PMID- 24851478
TI  - The effects of the Orff Approach on self-expression, self-efficacy, and social
      skills of children in low-income families in South Korea.
AB  - This experiment was designed to study the Orff Approach--a child-centered,
      developmental approach to music education that aims to enrich the imagination
      through the acceleration of psychological activities. The study was conducted in
      children who had exhibited problematic behavior possibly due to economical or
      psychological issues; it aimed to determine whether the Orff Approach satisfies
      educational and treatment purposes and is an acceptable alternative in improving
      self-expression, self-efficacy, and social skills. The experiment involved 43
      elementary school children in South Korean households with a monthly income of
      100% below the average (according to the National Basic Living Security Act,
      South Korea's Ministry of Health and Welfare), and the results showed an increase
      of the chil-dren's self-expression, self-efficacy, and social skills after
      musical activities with the Orff Approach. Also, children interacted with the
      musical activities--according to the Orff Approach--like a game.They noted that
      they were able to explain their thoughts and emotions better; their relationships
      with friends improved, as well. Therefore, this research is significant because
      it shows that musical activities according to the Orff Approach have
      possibilities to be utilized as a program for children's psychological and
      emotional support.

PMID- 24851480
TI  - SGR--fixable?

PMID- 24851481
TI  - Doing what's best isn't always easy.

PMID- 24851482
TI  - Is the end finally in sight for the Medicare SGR?

PMID- 24851483
TI  - When is brain dead not dead enough?

PMID- 24851484
TI  - Cranberry juice, atorvastatin and back pain.

PMID- 24851485
TI  - VAD: an under-recognized cause of stroke in the young.

PMID- 24851486
TI  - The Patients' Compensation Act (S.B. 141)--the wrong medicine for physicians in
      Georgia.

PMID- 24851487
TI  - Update: the Patient Protection And Affordable Care Act.

PMID- 24851488
TI  - HHS conclusion may enable providers to retain payments from insurers.

PMID- 24851489
TI  - Pain management rules in Georgia.

PMID- 24851490
TI  - Where we practice: West Georgia.

PMID- 24851491
TI  - Allergy immunotherapy: the first 100 years.

PMID- 24851492
TI  - Me and my journals.

PMID- 24851493
TI  - Next generation.

PMID- 24851494
TI  - My diabetes history.

PMID- 24851495
TI  - Respecting your elders.

PMID- 24851496
TI  - Big-time rush.

PMID- 24851497
TI  - Anatomy of a sensor. A look inside this cutting-edge diabetes device.

PMID- 24851498
TI  - Reaching goal.

PMID- 24851499
TI  - Not your type?

PMID- 24851500
TI  - Light & lovely. Honor the special women in your life with this elegant yet easy
      Mother's Day lunch.

PMID- 24851501
TI  - Safe to eat.

PMID- 24851502
TI  - Checklist to choose a health plan.

PMID- 24851503
TI  - Choosing the best plan for you: a tool for purchasing coverage in the health
      insurance exchange.

PMID- 24851504
TI  - Tools and tips for creating a positive work environment.

PMID- 24851505
TI  - HIPAA and the American Red Cross.

PMID- 24851506
TI  - Improving patient information leaflets: developing and applying an evaluative
      model of patient-centredness for text.
AB  - The purpose of this paper is to present an evaluative model of patient
      centredness for text and to illustrate how this can be applied to patient
      information leaflets (PILs) that accompany medication in the European Union.
      Patients have criticized PILs for sidelining their experiences, knowledge and
      affective needs, and denying their individuality. The health communication
      paradigm of patient-centredness provides valuable purchase on these issues,
      taking its starting point in the dignity and integrity of the patient as a
      person. Employing this evaluative model involves two stages. First, a Foucauldian
      Discourse Analysis is performed of sender and receiver and of the main discourses
      in PILs. These aspects are then evaluated using the perspectives of patient
      centredness theory relating to the medical practitioner, patient and content. The
      evaluative model is illustrated via a PIL for medication for depression and panic
      attacks. Evaluation reveals a preponderance of biomedical statements, with a
      cluster of patient-centred statements primarily relating to the construction of
      the patient. The paper contributes a new method and evaluative approach to PIL
      and qualitative health research, as well as outlining a method that facilitates
      the investigation of interdiscursivity, a recent focus of critical genre
      analysis.

PMID- 24851507
TI  - Experience of suicidal thoughts: a discourse analytic study.
AB  - In this paper we explore the relationship between current psychiatric thinking on
      suicide and service users' accounts of suicidal ideation and suicide attempts.
      The data comes from recordings of psychiatric interviews collected in three
      psychiatric hospitals in Poland. Assuming a constructionist view of discourse we
      argue that the literature on suicide ignores and simplifies the experience of
      those who think about suicide and attempt to commit it, and constructs their
      experiences as a homogeneous group of 'thoughts' with only limited content. We
      also offer a preliminary insight into the complexity of 'suicide thoughts', as
      narrated by those reporting them. We demonstrate that they are marginalized and
      made relatively irrelevant in the accounts of attempted suicide. Additionally, we
      demonstrate that while women construct suicide attempts (whether actually
      attempted in the end or not) as at least potentially beyond their control, men's
      narratives show them in control of the attempt, as if choosing an available
      option. We conclude by exploring possibilities of further qualitative discourse
      analytic research which builds on the findings we present here.

PMID- 24851508
TI  - The multiple meanings of 'disability' in interviews with amputees.
AB  - The link between having a lower-limb amputation and being disabled might seem
      self-evident. Indeed, the medical model of disability would suggest that lower
      limb amputation causes disability, and that all lower-limb amputees are disabled
      people. Conversely, social models of disability would argue that limb loss does
      not determine disability, but that disabilities are rather caused by social
      structures and prejudices, while the interactional model suggests that there are
      both individual and social causes of disability. This paper draws on interviews
      with nine lower-limb amputees to address amputees' own accounts of disability, in
      order to determine how (if at all) they make links between being an amputee and
      being disabled. The analysis shows that participants draw on various models of
      disability, as well as their own lived experiences, to construct subjective and
      diverse definitions of disability. Three interlinking definitions of disability
      recurred across the data: disability as a measure of personal (in)abilities;
      disability as a stigmatizing mask; and disability as an official status. Overall,
      disability was constructed as a complex, context-dependent label, which could not
      be reduced to any singular concept.

PMID- 24851509
TI  - Assumptions about culture in discourse on ethnic minority health.
AB  - This paper is interested in the way the concept of culture is deployed in
      documents aimed at investigating, informing on and promoting aspects of ethnic
      minority health. Within a health-political discourse focusing increasingly on
      individual lifestyles, ethnic minority health became subject to increased
      political and professional interest in the last decades of the twentieth and the
      first decade of the twenty-first century. Analysis of the discourse on ethnic
      minority health emerging in five texts addressing health professionals shows that
      the culture of ethnic minority citizens is primarily seen as contributing to low
      levels of knowledge about health and to adverse health behavior. Thus, the texts
      present cultural beliefs and practices as contributing to the high prevalence of
      lifestyle diseases among ethnic minority population groups. The analysis,
      however, demonstrates that a more nuanced discourse is evolving, taking the
      complexity of the culture concept into account. In accordance with Danish health
      political priorities, the most recent text analyzed in this study promotes an
      individualistic approach to both ethnic minority and Danish ethnic majority
      citizens.

PMID- 24851510
TI  - Misunderstandings, communicative expectations and resources in illness
      narratives: insights from beyond interview transcripts.
AB  - Interactional misunderstandings in interviews are often glossed over in analysing
      narratives, so overlooking important clues about how interactants frame the
      interview discussion. Such misunderstandings will influence ongoing talk, shaping
      knowledge researchers produce about participants. We discuss whether
      interpretations of illness narratives may be enhanced if we analyse
      misunderstandings in conjunction with other contextually-available data not
      visible within interview transcripts. Using research interviews with people with
      asthma, we adopted linguistic-ethnographic methods to analyse the manifestation
      and specific consequences of interactional tensions and misunderstandings between
      interviewer and interviewee. Misunderstandings can indicate inequalities in
      communicative expectations and discursive resources available to interactants,
      which may lead to participants' talk being inappropriately identified as
      indicating a particular narrative. Incorporating ethnographic contextual features
      may make visible pertinent discourses not overtly evident within interviews. This
      may help theorize interview talk, like health and illness narratives, as
      manifesting within cycles of discourse that will intersect differently in each
      interaction.

PMID- 24851511
TI  - Movie dialogues as discourse data in the study of forecasting mechanisms in the
      delivery of medical bad news.
AB  - Understanding the communication skills for delivering bad news, an important
      daily task for medical professionals, presents a challenge for most researchers
      due to methodological and ethical dilemmas. Movie dialogues, in which difficult
      communication of life-and-death issues are fundamental ingredients in creating
      dramatic effects, are often adopted in medical education and are thus potential
      data for study. By applying the concept of forecasting mechanism' in bad news
      delivery (Schegloff 1988; Maynard 2003), this study examines bad news delivery
      events depicted in three movie clips. My analysis demonstrates that (1)
      forecasting, as a 'macro conversation mechanism', is observed in both natural and
      artificial discourses; (2) two subtypes of forecasting are identifiable in movie
      dialogues:forecasting that directs the interaction to a 'recipient-leading-the
      telling' pattern, and forecasting that constructs the delivery event as one with
      shared agency; and (3) the two subtypes may facilitate the deliverer's task by
      minimizing conflicting perspectives with the recipient, ensuring the recipient's
      orientation to the bad news, and freeing the deliverer from the pressure of being
      blamed. These findings indicate the possibility of applying movie clips in
      discourse research and medical education in regard to conversational strategies
      for difficult communication.

PMID- 24851512
TI  - Communicating moral reasoning in medicine as an expression of respect for
      patients and integrity among professionals.
AB  - The communication of moral reasoning in medicine can be understood as a means of
      showing respect for patients and colleagues through the giving of moral reasons
      for actions. This communication is especially important when disagreements arise.
      While moral reasoning should strive for impartiality, it also needs to
      acknowledge the individual moral beliefs and values that distinguish each person
      (moral particularity) and give rise to the challenge of contrasting moral
      frameworks (moral pluralism). Efforts to communicate moral reasoning should move
      beyond common approaches to principles-based reasoning in medical ethics by
      addressing the underlying beliefs and values that define our moral frameworks and
      guide our interpretations and applications of principles. Communicating about
      underlying beliefs and values requires a willingness to grapple with challenges
      of accessibility (the degree to which particular beliefs and values are
      intelligible between persons) and translatability (the degree to which particular
      beliefs and values can be transposed from one moral framework to another) as
      words and concepts are used to communicate beliefs and values. Moral dialogues
      between professionals and patients and among professionals themselves need to be
      handled carefully, and sometimes these dialogues invite reference to underlying
      beliefs and values. When professionals choose to articulate such beliefs and
      values, they can do so as an expression of respectful patient care and
      collaboration and as a means of promoting their own moral integrity by signaling
      the need for consistency between their own beliefs, words and actions.

PMID- 24851513
TI  - Using videoed simulated clinical interaction to promote communication skills and
      reflective practice for overseas-born medical students.
AB  - This paper describes a teaching intervention designed to promote the clinical
      communications skills of overseas-born medical students through critical
      reflection on the practice of others. Using a staged process and a video
      recording of a simulated medical interaction it investigated the extent to which
      the participants were able to anticipate, identify and resolve the targeted
      communication issues, and demonstrate selected skills in a simulated interaction.
      Data comprised worksheet notes, transcriptions (group discussions) and completed
      questionnaires (ratings and comments). Analysis was thematic (worksheet notes,
      transcription, questionnaire feedback) and quantitative (questionnaire ratings).
      The results suggest the notion of reflective practice could be productively
      extended to take account of current developments in pedagogy and learning. This
      includes providing opportunities for students to share ideas, resolve differences
      and ambiguities, and address gaps in their communication skills as well as to
      apply learned concepts and receive targeted feedback. While the intervention
      specifically targeted overseas-born medical students, the approach described in
      the paper has potential for developing the communication skills of 'local'
      medical students and healthcare professionals more generally.

PMID- 24851514
TI  - The patient's Lifeworld: building meaningful clinical encounters between
      patients, physicians and interpreters.
AB  - In this paper, our objectives are first to explore the different ways physicians
      and interpreters interact with patients' Lifeworld, and second, to describe and
      compare communication patterns in consultations with professional and those with
      family interpreters. We conducted analyses of transcriptions of 16 family
      practice consultations in Montreal in the presence of interpreters. Patterns of
      communication are delineated, grounded in Habermas' Communicative Action Theory
      and Mishler's operational concepts of Voice of Medicine and Voice of Lifeworld.
      Four communication patterns emerged: (1) strategically using Lifeworld data to
      achieve biomedical goals; (2) having an interest in the Lifeworld for itself; (3)
      integrating the Lifeworld with biomedicine; and (4) referring to another
      professional. Our results suggest physicians engage with patients' Lifeworld and
      may benefit from both types of interpreters' understanding of the patient's
      specific situations. A professional interpreter is likely to transmit the
      patient's Lifeworld utterances to the physician. A family member, on the other
      hand, may provide extra biomedical and Lifeworld information, but also prevent
      the patient's Lifeworld accounts from reaching the physician. Physicians'
      training should include advice on how to work with all types of interpreters and
      interpreters' training should include mediation competencies in order to enhance
      their ability to promote the processes of co-construction of meaning.

PMID- 24851515
TI  - Admirable dishonesty in medical practice.
AB  - Historically, the ethics of dishonesty within the physician-patient relationship
      has been analyzed largely from the deontological and consequentialist viewpoints.
      In this essay I offer a new exploration of dishonesty from the recently developed
      Virtue Ethics of Care perspective. First, I will explain and justify a general
      prescription for honest conduct within the relationship. Next, I will explore the
      conditions under which the Virtue Ethics of Care would find acts of dishonesty in
      medical practice to be admirable. Here, the moral distinction between lying and
      deception will be discussed. Then, two special contexts in medical practice,
      paternalistic dishonesty and patient dishonesty, will be analyzed. I will close
      with a discussion of the role of trust in the relationship and how it acts to
      prevent the Virtue Ethics of Care from sliding down the path toward objectionable
      acts of dishonesty.

PMID- 24851516
TI  - Depression, sense and sensitivity: on pre-diagnostic questioning about self-harm
      and suicidal inclination in the primary care consultation.
AB  - National Health Service directives in the UK specify that, in any primary care
      consultation where a patient either demonstrably has--or is suspected to have-
      depression, a 'direct question' should be asked regarding their thoughts or
      activities relating to self-harm or suicide. The evidence collected for this
      study, which takes the form of recorded interactions between doctors and patients
      in primary care settings, indicates that this is most commonly done post
      diagnosis as an exercise in 'risk assessment' Suicidal ideation, however, is not
      only classified as a possible outcome of depression but also a core symptom of
      the condition and, consequently, such a question is sometimes asked prior to the
      diagnostic phase of the consultation, as a key step in reaching a depression
      diagnosis. This specific activity presents a general practitioner with an
      inferably difficult communicative task: how to raise the matter of suicide/self
      harm when the patient does not already have a depression diagnosis as an
      interactional resource with which to make sense of its local relevance. Herein,
      using a conversation analytic method, techniques employed by general
      practitioners and patients in negotiating three of these potentially sensitive
      moments are examined. Analytic observations are then used to highlight a range of
      issues pertinent to the formulation of normative frames of 'good practice' in
      handling difficult clinical topics in situ.

PMID- 24851517
TI  - Pain and nurses' emotion work in a paediatric clinic: treatment procedures and
      nurse-child alignments.
AB  - In the treatment of cancer in children, treatment procedures have been reported
      to be one of the most feared elements, as more painful than the illness as such.
      This study draws on a video ethnography of routine needle procedure events, as
      part of fieldwork at a paediatric oncology clinic documenting everyday treatment
      negotiations between nurses and young children. On the basis of detailed
      transcriptions of verbal and nonverbal staff-child interaction, the analyses
      focus on ways in which pain and anxiety can be seen as phenomena that are partly
      contingent on nurses' emotion work. The school-age children did not display fear.
      In the preschool group, though, pain and fear seemed to be phenomena that were
      greatly reduced through nurses' emotion work. This study focuses on three
      preschoolers facing potentially painful treatment, showing how the nurses engaged
      in massive emotion work with the children, through online commentaries,
      interactive formats (delegation of tasks, consent sequences, collaborative 'we'
      formats), as well as solidarity-oriented moves (such as praise and endearment
      terms). Even a young toddler would handle the distress of needle procedures, when
      interacting with an inventive nurse who mobilized child participation through
      skilful emotion work.

PMID- 24851518
TI  - Titling and authorship practices in medical case reports: a diachronic study
      (1840-2009).
AB  - This paper is a diachronic analysis of a corpus of 180 titles drawn from Case
      Reports (CRs) published in the BMJ and BMJ Case Reports between 1840 and 2009.
      The corpus was divided into three blocks, and the frequency of occurrence of 69
      text-internal variables was recorded in each title. Between-block comparisons
      were carried out, and Student's t-tests were applied to the quantitative results.
      Our findings show that CR titles have evolved over the 160-year period studied in
      the sense that they have increased in length, syntactic complexity, semantic
      richness and title-type diversity. Authorship patterns and collaboration
      practices have changed too. Although internationalization of case reporting has
      increased over time, today's preferred practice is still local collaboration. The
      only variable that has remained constant over the years is the nominal nature of
      CR titles. We put forth several social and scientific factors that could account
      for the various shifts observed. We claim that non-informativeness of CR titles
      that persisted over time can be explained by the fact that CR authors are
      reluctant to give a generalization flavor to their findings.

PMID- 24851519
TI  - Stress management: corpus-based insights into vernacular interpretations of
      stress.
AB  - Examination of the term stress in naturally occurring vernacular prose provides
      evidence of three separate senses being conflated. A corpus analysis of 818
      instances of stress from non-academic texts in the Corpus of Contemporary
      American English (COCA) and the Corpus of American Discourses on Health (CADOH)
      shows a negative prosody for stress, which is portrayed variously as a source
      outside the body, a physical symptom within the body and an emotional state. The
      data show that contemporary speakers intermingle the three senses, making more
      difficult a discussion between doctors and patients of ways to 'reduce stress:
      when stress might be interpreted as a stressor, a symptom, or state of anxiety.
      This conflation of senses reinforces the impression that stress is pervasive and
      increasing. In addition, a semantic shift is also refining a new sense for
      stress, as post-traumatic stress develops as a specific subtype of emotional
      stress whose use has increased in circulation in the past 20 years.

PMID- 24851520
TI  - Intestinal permeabililty in portal hypertension: still a dilemma.

PMID- 24851521
TI  - Recurrent acute pancreatitis: an approach to diagnosis and management.
AB  - Recurrent acute pancreatitis (RAP) is defined as more than two attacks of acute
      pancreatitis (AP) without any evidence of underlying chronic pancreatitis (CP).
      As the known causes of AP are generally taken care of, RAP usually occurs in the
      idiopathic group, which forms 20%-25% of cases of AP. The causes of idiopathic
      RAP (IRAP) can be mechanical, toxic-metabolic, anatomical, or miscellaneous.
      Microlithiasis commonly reported from the West is not a common cause of IRAP
      among Indian patients. Pancreas divisum (PD) is now believed as a cofactor, the
      main factor being associated genetic mutations. The role of Sphincter of Oddi
      dysfunction (SOD) as a cause of IRAP remains controversial. Malignancy should be
      ruled out in any patient with IRAP > 50 years of age. Early CP can present
      initially as RAP. The work-up of patients with IRAP includes a detailed history
      and investigations. Primary investigations include liver function tests (LFT),
      serum calcium and triglyceride, abdominal ultrasonography (USG) and contrast
      ehhanced computed tomography (CECT) abdomen. Endoscopic ultrasound (EUS),
      magnetic resonance cholangiopancreatography (MRCP) and possibly endoscopic
      retrograde cholangiopancreatography (ERCP) are indicated in the secondary phase
      if the work-up is negative after the primary investigations. EUS is advised
      usually 6-8 weeks after an acute episode. Treatment of patients with IRAP is
      aimed at the specific aetiology. In general, empirical cholecystectomy should be
      discouraged with the availability and widespread use of EUS. Endoscopic
      sphincterotomy is advised if there is strong suspicion of SOD. Minor papilla
      sphincterotomy should be carried out in those with PD but with limited
      expectations. Regular follow-up of patients with IRAP is necessary because most
      patients are likely to develop CP in due course.

PMID- 24851522
TI  - Frequency and factors associated with increased small intestinal permeability in
      patients with portal hypertension.
AB  - AIM: Cirrhosis with portal hypertension (PHT) may be associated with increased
      small intestinal permeability (SIP), predisposing to malnutrition and bacterial
      translocation causing septicaemia, endotoxaemia and spontaneous bacterial
      peritonitis. However, data on SIP in extrahepatic portal venous obstruction
      (EHPVO), in which PHT occurs without hepatic dysfunction, are scanty. Such
      studies would help to know the effect of PHT on SIP independent of hepatic
      dysfunction; hence, we undertook this study. METHODS: A total of 96 patients with
      PHT (cirrhosis 71, EHPVO 25) underwent evaluation of SIP using urinary
      lactulose/mannitol excretion ratio over 6 hours after oral administration of 15
      mL (10 g) lactulose and 5 g mannitol using 1H-NMR spectroscopy by a method
      described by us previously. RESULTS: Gender of patients with EHPVO and cirrhosis
      was comparable but patients with EHPVO were younger in age. The causes of
      cirrhosis were cryptogenic (n = 22), alcohol (n = 20), post-viral (n = 21) and
      others (n = 8). Twenty-seven (38%) patients with cirrhosis had ascites. Abnormal
      SIP was detected in 47 (49%) patients (40/71,56% with cirrhosis vs. 7/25, 28%
      with EHPVO, p = 0.01). Patients with cirrhosis had a higher urinary
      lactulose/mannitol excretion ratio than those with EHPVO (0.09, range 0-0.87 mmol
      vs. 0.05, 0-0.19 mmol; p = 0.008). Patients with abnormal SIP had a higher Child
      score, and more often had cirrhosis than EHPVO, ascites and deranged liver
      function. On multivariate analysis, presence of cirrhosis, ascites, high serum
      bilirubin level and prothrombin time were associated with abnormal SIP.
      CONCLUSIONS: Cirrhosis was associated with abnormal SIP, which was related to
      liver dysfunction. However, SIP was normal in patients with EHPVO.

PMID- 24851523
TI  - Profile of patients with incidentally detected nonalcoholic fatty liver disease
      (IDNAFLD) in coastal eastern India.
AB  - BACKGROUND AND AIM: Non-alcoholic fatty liver disease (NAFLD) has emerged as the
      commonest hepatic problem in both developed and developing countries. This study
      was conducted to delineate the clinical profile of incidentally detected NAFLD
      patients. METHODS: A retrospective analysis of clinical, biochemical and
      histological parameters was performed for 632 patients in whom fatty liver was
      diagnosed by ultrasonography during 2006-2010. Every patient's clinical
      presentation, history, liver function tests, blood sugar, lipid profile,
      ultrasonogram, histology and other relevant investigations were analyzed.
      Patients referred for transaminitis or overt chronic liver disease were excluded.
      RESULTS: Out of 632 consecutive NAFLD patients, 484 (76.6%) were males and 148
      (23.4%) were females. Mean age of our patients was 42.44 +/- 10.18 years. Their
      mean body mass index (BMI) was 26.14 +/- 3.38 kg/m2. Obesity (BMI > 25), diabetes
      mellitus, hypertension, hyperlipidemia, metabolic syndrome and insulin resistance
      were present in 61.7%, 15.2%, 19.8%, 62.0%, 40.0%, and 54.4% patients,
      respectively. SGOT and SGPT were elevated in 38.29% and 55.1% patients,
      respectively. The common primary diseases for which these patients sought
      consultation were non-ulcer dyspepsia (NUD) (54.5%) and irritable bowel syndrome
      (IBS) (29.4%). Of the 64 patients who underwent liver biopsy, one-fourth had
      definite NASH while one-third patients had fibrosis. CONCLUSION: In India,
      incidentally detected NAFLD (IDNAFLD) patients are predominantly middle aged
      males, most of whom are not lean. Most of these patients seek consultation for
      functional bowel disease.

PMID- 24851524
TI  - Non-alcoholic fatty liver disease among visitors to a hepatitis awareness
      programme.
AB  - BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) is rapidly
      becoming the most common liver disease worldwide. The present study aimed to
      evaluate the prevalence of NAFLD among the visitors screened on World Hepatitis
      Day 2010 and 2011. METHODS: Attendees of the hepatitis awareness programme (n =
      928) were offered screening to rule out liver ailments. The participants were
      evaluated on history, body mass index (BMI) measurement, blood tests for
      hepatitis B surface antigen (HBsAg), anti-hepatitis C virus (anti-HCV), alanine
      aminotransferase (ALT) levels and abdominal ultrasound (US). RESULTS: On
      ultrasonography, fatty liver was present in 142 of 806 subjects who were found
      negative for viral serology and had no history of regular alcohol intake. This
      accounted for 15.3% of all the visitors. Comparing them with the rest of the
      serology-negative alcohol-negative subjects, there were more housewives (p =
      0.005) with fatty liver. They were older with mean age 43.3 +/- 12.1 years
      compared to 33.1 +/- 16.1 years (p = 0.000) in patients without fatty liver and
      had a higher BMI 28.6 +/- 6.0 kg/m2 vs. 22.2 +/- 5.3 kg/m2 (p = 0.000).
      Regression analysis suggested BMI as the only significant independent risk factor
      (p = 0.000). However, 32 subjects with fatty liver had BMI < 25 kg/m2 and 6 of
      them had diabetes mellitus. Thirty-one subjects (21.8%) with fatty liver had
      raised ALT level (p = 0.000) and possible non-alcoholic steatohepatitis (NASH)
      which accounts for 3.34% (31/928) of the total visitors. CONCLUSIONS: This
      analysis reveals that our general population is at risk of having NAFLD and NASH
      and these should be looked into even in non-obese persons.

PMID- 24851525
TI  - Risk of development of hepatocellular carcinoma in patients with NASH-related
      cirrhosis.
AB  - BACKGROUND AND AIMS: The risk of development of hepatocellular carcinoma (HCC) in
      hepatitis B virus (HBV) and hepatitis C virus (HCV) infection is well established
      and is being recognized increasingly in non-alcoholic steatohepatitis (NASH)
      related cirrhosis. This study aimed to assess the risk of development of HCC in
      patients with NASH-related cirrhosis. METHODS: From January 2010 to October 2011,
      we prospectively enrolled 585 patients with liver cirrhosis (men:women ratio
      4.4:1, mean age 50.1 +/- 6.1 years, aetiology HBV 19%, HCV 14.2%, NASH-related
      7%, cryptogenic cirrhosis 17.8%, already diagnosed cirrhosis 48.2%, and the
      remaining were newly diagnosed cases). The cumulative follow-up was for 5.9 +/-
      0.5, 6.1 + 0.8 and 6.8 + 1.2 years for HBV, HCV and NASH-related cirrhosis,
      respectively. Patients with advanced cirrhosis, Child class C and associated
      comorbid conditions where survival was < 1 year were excluded from the study. The
      remaining patients were followed up 6-monthly with ultrasound examination and
      alpha-fetoprotein (AFP) test. Patients suspected of HCC underwent triple-phase
      computed tomography (CT) scan and liver biopsy was done to confirm the diagnosis.
      RESULTS: A total of 54 patients developed HCC, of which 26 had HBV, 14 had HCV, 9
      had- cryptogenic and 6 had- NASH-related cirrhosis. The annual rate of
      development of HCC was 1.5%, 3.6%, 0.6% and 0.46 in HBV, HCV, cryptogenic and
      NASH-related cirrhosis, respectively. CONCLUSIONS: The incidence of HCC was
      highest in HCV and lowest in NASH-related cirrhosis. These figures suggest an
      intermediate risk of development of HCC when compared to western countries and
      Japan.

PMID- 24851526
TI  - Serogroup distribution of Shigella in Ile-Ife, southwest Nigeria.
AB  - BACKGROUND: Shigellosis is endemic throughout the world and Shigella spp. is
      among the most common pathogens responsible for bacterial diarrhoeal diseases.
      Death attributed to shigellosis is common in developing countries, where affected
      populations are immunologically compromised due to poor nutrition and background
      infections. AIM: To investigate the serogroup distribution of Shigella spp.
      recovered from clinically diagnosed cases of gastroenteritis and acute diarrhoea
      among children (0-5 years) in Ile-Ife, southwest Nigeria between September 2003
      and September 2006. METHODS: The isolates were identified and characterized
      biochemically and serologically. RESULTS: Out of 102 Shigella isolates
      identified, 45 (44%) were S. flexneri, 26 (25%) were S. dysenteriae, 19 (19%)
      were S. boydii, 6 (6%) were S. sonnei and 6 (6%) were untypable strains.
      CONCLUSIONS: We conclude that Shigella serogroups can be considered an important
      aetiological agent of acute diarrhoea and mortality among children in Ile-Ife,
      southwest Nigeria.

PMID- 24851527
TI  - Role of diagnostic laparoscopy in chronic and recurrent abdominal pain.
AB  - BACKGROUND: Chronic abdominal pain is a very common condition presenting to a
      general surgeon. It is defined as pain lasting for more than 3 months. Sometimes,
      the diagnosis cannot be established even with the help of advanced radiological
      investigations. This study aims to define the role of laparoscopy in diagnosing
      the cause of chronic abdominal pain and thus enabling a definitive management.
      METHODS: The study included 52 patients admitted to the Department of Surgery,
      Himalayan Institute of Medical Sciences, Dehradun, India for chronic abdominal
      pain of unknown origin. All patients underwent diagnostic laparoscopy with
      methodical inspection of the whole abdomen. RESULTS: Diagnosis was established in
      86.5% of cases either by direct visualization or histopathological examination.
      The most common pathology was chronic appendicitis (19%) followed by adhesions
      (17.3%) and peritoneal tuberculosis (15.3%). A therapeutic procedure was done in
      46% of cases during laparoscopy. No major complication was reported during the
      study. CONCLUSIONS: Laparoscopy is a safe and effective method to diagnose the
      cause of chronic abdominal pain in cases where other non-invasive methods prove
      unreliable.

PMID- 24851528
TI  - Mesenteric haematoma or tear is the criminal.

PMID- 24851529
TI  - Strongyloidiasis--a forerunner of adult T-cell lymphoma.

PMID- 24851530
TI  - Tubercular pancreatic abscess: diagnostic dilemma and management.

PMID- 24851531
TI  - Malignant paraganglioma of the bile duct.

PMID- 24851532
TI  - Perivascular epithelioid cell tumour of the duodenum.

PMID- 24851533
TI  - Should gut malrotation be suspected in adolescents and young adults presenting
      with failure to thrive?

PMID- 24851534
TI  - Intracranial fungal infections in chronic liver disease: a report of two cases.

PMID- 24851535
TI  - Endometriosis causing small bowel obstruction.

PMID- 24851536
TI  - Non-traumatic rupture of malarial spleen.

PMID- 24851537
TI  - Enteral stenting using the rendezvous technique.

PMID- 24851538
TI  - Reflux disease in an infant: a twist in the tale.

PMID- 24851539
TI  - Primary gastric combined adeno- small cell neuroendocrine carcinoma.

PMID- 24851540
TI  - Chronic hepatic abscess due to gallbladder perforation: three cases and exact
      nomenclature.

PMID- 24851541
TI  - Isolated periampullary tuberculosis: masquerading as periampullary carcinoma.

PMID- 24851542
TI  - Chronic encapsulating peritonitis or cocoon abdomen.

PMID- 24851543
TI  - How and why hyperbaric oxygen therapy can bring new hope for children suffering
      from cerebral palsy--an editorial perspective.

PMID- 24851544
TI  - Intensive rehabilitation combined with HBO2 therapy in children with cerebral
      palsy: a controlled longitudinal study.
AB  - OBJECTIVE: The present study aimed to assess the effect of intensive
      rehabilitation combined with hyperbaric oxygen (HBO2) therapy on gross motor
      function in children with cerebral palsy (CP). METHODS: We carried out an open,
      observational, platform-independent study in 150 children with cerebral palsy
      with follow-up over eight months to compare the effects of standard intensive
      rehabilitation only (control group n = 20) to standard intensive rehabilitation
      combined with one of three different hyperbaric treatments. The three hyperbaric
      treatments used were: air (FiO2 = 21%) pressurized to 1.3 atmospheres
      absolute/atm abs (n = 40); 100% oxygen pressurized at 1.5 atm abs (n = 32); and
      100% oxygen, pressurized at 1.75 atm abs (n = 58). Each subject assigned to a
      hyperbaric arm was treated one hour per day, six days per week during seven weeks
      (40 sessions). Gross motor function measure (GMFM) was evaluated before the
      treatments and at two, four, six and eight months after beginning the treatments.
      RESULTS: All four groups showed improvements over the course of the treatments in
      the follow-up evaluations (p < 0.001). However, GMFM improvement in the three
      hyperbaric groups was significantly superior to the GMFM improvement in the
      control group (p < 0.001). There was no significant difference between the three
      hyperbaric groups. CONCLUSION: The eight-month-long benefits we have observed
      with combined treatments vs. rehabilitation can only have been due to a
      beneficial effect of hyperbaric treatment.

PMID- 24851545
TI  - Hyperbaric oxygen treatment for post-radiation central nervous system injury: a
      retrospective case series.
AB  - Increased use of radiation therapy and increasing life spans following radiation
      treatment has led to an increase in the finding of post-radiation central nervous
      system injury in patients who have previously undergone radiation treatments. At
      this time, information regarding treatment for patients suffering from this
      serious side effect is limited and not readily available. It is imperative to
      examine possible treatment options, complications and success rates for these
      patients. This retrospective review will look at 10 patients who underwent
      hyperbaric oxygen therapy for post-radiation injury to the central nervous
      system. Review and investigation of the subjective, clinical and radiologic
      outcomes of these patients was conducted. It was determined that for patients
      with post-radiation central nervous system injury it is important to distinguish
      the exact diagnosis for each patient. For those patients with radiation necrosis,
      conclusion was made that hyperbaric oxygen (HBO2) therapy does lead to
      improvement in subjective, clinical and radiologic outcomes. However, the results
      were not consistent across all patients. For those patients with non-specific
      delayed radiation injury, findings showed that HBO2 does not lead to any
      improvement. Therefore, we conclude that for those patients who have been
      diagnosed with radiation necrosis of the central nervous system, we recommend
      HBO2 therapy as a potential treatment option for some patients.

PMID- 24851546
TI  - Effects of scuba diving on vascular repair mechanisms.
AB  - A single air dive causes transient endothelial dysfunction. Endothelial
      progenitor cells (EPCs) and circulating angiogenic cells (CAC) contribute
      synergistically to endothelial repair. In this study (1) the acute effects of
      diving on EPC numbers and CAC migration and (2) the influence of the gas mixture
      (air/nitrox-36) was investigated. Ten divers performed two dives to 18 meters on
      Day (D) 1 and D3, using air. After 15 days, dives were repeated with nitrox-36.
      Blood sampling took place before and immediately after diving. Circulating EPCs
      were quantified by flow cytometry, CAC migration of culture was assessed on D7.
      When diving on air, a trend for reduced EPC numbers is observed post-dive, which
      is persistent on D1 and D3. CAC migration tends to improve acutely following
      diving. These effects are more pronounced with nitrox-36 dives. Diving acutely
      affects EPC numbers and CAC function, and to a larger extent when diving with
      nitrox-36. The diving-induced oxidative stress may influence recruitment or
      survival of EPC. The functional improvement of CAC could be a compensatory
      mechanism to maintain endothelial homeostasis.

PMID- 24851547
TI  - The relevance of magnetic resonance imaging in spinal cord decompression
      sickness: a survey of seven cases.
AB  - To investigate the magnetic resonance imaging (MRI) features of spinal cord
      decompression sickness (DCS) on compressed-air divers, we hereby report seven
      cases diagnosed with spinal cord DCS. Only two patients out of seven showed
      positive MRI findings: A detailed case report will be provided on each. In one of
      the cases, the MRI revealed extensive high signal within the central gray matter
      of the spinal cord. The other one showed patchy high signal on T2-weighted images
      as well as diffusion-weighted images (DWI) in the dorsal column white matter of
      the spinal cord. The findings in our collective suggest that the MRI focused on
      the spinal cord is not always appropriate for obtaining a quick diagnosis. The
      discrepancy between MRI findings and clinical evolution leads to the conclusion
      that MRI focused on the spinal cord does not always correlate with neurological
      improvement. Decision for hyperbaric oxygen (HBO2) treatment should not be based
      primarily on MRI findings.

PMID- 24851548
TI  - The impact of freediving on psychomotor performance and blood catecholamine
      concentration.
AB  - The aim of the study was to investigate the effects of breath-hold diving on
      divers' psychomotor performance and blood adrenaline, noradrenaline and lactate
      concentrations. Four male divers took part in the experiment. During the study
      the divers' choice reaction time as well as plasma concentration of adrenaline,
      noradrenaline and lactate were measured. The measurements were carried out before
      immersion (before a warm-up), three minutes after the dive, and 60 minutes after
      the dive. A reduction in the reaction time to audiovisual stimuli was found in
      three divers, three minutes after the dive. Diver 4, who broke his personal best
      record, had a longer choice reaction time at three minutes after the dive. The
      adrenaline concentration was lowered in Diver 1 and Diver 2, at three minutes
      after the dive. The adrenaline level in Diver 3 was relatively steady at all test
      measurements. In Diver 4, who broke his personal best, a twofold increase in
      adrenaline concentration was noted at three minutes after the dive. All examined
      divers revealed an increase in noradrenaline blood level at three minutes after
      the dive. The results of the study are of great practical value since disturbed
      reactions during freediving can put the diver at the risk of serious barotraumas.

PMID- 24851549
TI  - A retrospective cohort study of lidocaine in divers with neurological
      decompression illness.
AB  - Lidocaine is the most extensively studied substance for adjuvant therapy in
      neurological decompression illness (DCI), but results have been conflicting. In
      this retrospective cohort study, we compared 14 patients who received adjuvant
      intravenous lidocaine for neurological decompression sickness and cerebral
      arterial gas embolism between 2001 and 2011 against 21 patients who were treated
      between 1996 and 2001 and did not receive lidocaine. All patients were treated
      with hyperbaric oxygen (HBO2) therapy according to accepted guidelines. Groups
      were comparable for all investigated confounding factors, except that
      significantly more control patients had made an unsafe dive (62% vs. 14%, p =
      0.007). Groups had comparable injury severity as measured by Dick and Massey
      score (lidocaine 2.7 +/- 1.7, control 2.0 +/- 1.6), an adapted version of the
      Dick and Massey score, and the Blatteau score. Number of HBO2 sessions given was
      comparable in both groups (lidocaine 2.7 +/- 2.3, control 2.0 +/- 1.0). There was
      neither a positive nor a negative effect of lidocaine on outcome (relative risk
      for objective neurological signs at follow-up in the lidocaine group was 1.8, 95%
      CI 0.2-16). This is the first retrospective cohort study of lidocaine in
      neurological DCI. Since our study is under-powered to draw definitive
      conclusions, a prospective multicenter study remains the only way to reliably
      determine the effect of lidocaine in neurological decompression illness.

PMID- 24851550
TI  - Prevalence of cardiomegaly and left ventricular hypertrophy in scuba diving and
      traffic accident victims.
AB  - Although frequently asymptomatic, left ventricular hypertrophy (LVH) is an
      independent predictor of sudden cardiac death (SCD). We hypothesized that diving
      may increase the propensity for pre-existent LVH to cause a lethal arrhythmia
      (and SCD) and therefore the prevalence of LVH may be greater among scuba
      fatalities than among traffic fatalities. We compared autopsy data for 100 scuba
      fatalities with 178 traffic fatalities. Extracted data contained information on
      age, sex, height, body mass, heart mass (HM), left ventricular wall thickness
      (LVWT), interventricular wall thickness (IVWT), and degree of coronary artery
      stenosis. A case was classified as LVH if the LVWT was > 15 mm. Log risk models
      were used to compare HM and LVWT in two groups while controlling for body mass,
      body length, age and sex. The prevalence of LVH was compared using Pearson's
      test. The mean HM was 428.3 +/- 100 for divers and 387 +/- 87 for controls. The
      crude HM ratio for scuba fatalities vs. controls was 1.11 (1.05, 1.17), and when
      controlled for sex, age and body mass the ratio was 1.06 (1.01, 1.09). The mean
      LVWT was 15 +/- 3.5 for divers and 14 +/- 2.7 for controls (p = 0.0017). HM and
      LVWT measured at autopsy were greater in scuba than in traffic fatalities.

PMID- 24851551
TI  - Multilocus sequencing typing of Pseudomonas aeruginosa isolates and analysis of
      potential pathogenicity of typical genotype strains from occupational oxyhelium
      saturation divers.
AB  - BACKGROUND: Pseudomonas aeruginosa (P. aeruginosa) is a common microbe isolated
      from divers with ear and skin infections. To obtain the epidemic characters of
      the occurrence of the P. aeruginosa infection, multilocus sequence typing (MLST)
      was used to assess the genetic background of different strains isolated from
      divers involved in saturation diving. METHODS: A total of 64 P. aeruginosa
      strains from naval divers were sequenced by multilocus sequence typing using
      seven housekeeping genes (acsA, aroE, guaA, mutL, nuoD, ppsA and trpE). The
      results were analyzed based on the P. aeruginosa international MLST database to
      obtain the allelic profiles and sequence types (STs). MLST data were analyzed by
      Bionumerics 4.0 (http: // pubmlst.org/mlstanalyse) using LIAN and eBURST. Twenty
      eight strains with the typical genotype were selected for further analysis of
      pathogenic characteristics by Caenorhabditis elegans (C. elegans) fast killing
      model. RESULTS: Data from MLST revealed a high STs diversity among the strains.
      Of the 64 strains, 53 strains were assigned to 19 STs, and the remaining 11
      clones could not be assigned. ST274 accounted for 18.5% (12/64), and ST260
      accounted for 15.62% (10/64). C. elegans killing assay showed that all the test
      strains had distinct virulent properties as compared with the negative control
      group. Clone 503-1 had the highest virulence and clone 54 had the lowest
      virulence as compared with the positive clinical group. CONCLUSION: The P.
      aeruginosa strains carried by the occupational diver groups in Chinese regions
      have characteristically dominant STs, and have a relatively strong virulence as
      compared with the standard strain and the clinically isolated positive control
      strain.

PMID- 24851552
TI  - Skin-sparing mastectomy flap ischemia salvage using urgent hyperbaric chamber
      oxygen therapy: a case report.
AB  - Since its introduction in 1991, skin-sparing mastectomy has emerged as an
      acceptable surgical technique in the management of breast cancer patients,
      providing optimal oncological safety and efficacy with favorable aesthetic
      results. Rates of native skin flap ischemia and necrosis after skin-sparing
      mastectomy are 2%-30% and result in a decreased aesthetic outcome and delay of
      necessary adjuvant treatment. Hyperbaric oxygen therapy has been advocated for
      the management of various compromised flaps, and when instituted immediately
      postoperatively, may prevent progression of ischemia into necrosis. We report the
      case of a 41-year-old female who developed skin flap ischemia after undergoing
      skin-sparing mastectomy and was immediately treated with hyperbaric oxygen. The
      patient received a total of five hyperbaric oxygen therapy sessions, achieving
      full resolution of the ischemia without any complications. Further research is
      essential to determine the role of hyperbaric oxygen therapy in managing skin
      flap ischemia post skin-sparing mastectomy. Until such studies exist, hyperbaric
      oxygen therapy may be considered a preferred option in the management of native
      skin flap ischemia after skin-sparing mastectomy.

PMID- 24851553
TI  - Hyperbaric oxygen treatment for decompression sickness.
AB  - Decompression sickness (DCS) is a clinical syndrome occurring usually within 24
      hours of a reduction in ambient pressure. DCS occurs most commonly in divers
      ascending from a minimum depth of 20 feet (6 meters) of sea water, but can also
      occur during rapid decompression from sea level to altitude (typically > 17,000
      feet / 5,200 meters). Manifestations are one or more of the following: most
      commonly, joint pain, hypesthesia, generalized fatigue or rash; less common but
      more serious, motor weakness, ataxia, pulmonary edema, shock and death. The cause
      of DCS is in situ bubble formation in tissues, causing mechanical disruption of
      tissue, occlusion of blood flow, platelet activation, endothelial dysfunction and
      capillary leakage. High inspired concentration of oxygen (O2) is recommended as
      first aid for all cases and can be definitive treatment for most altitude DCS.
      For most other cases, hyperbaric oxygen is recommended,most commonly 100% O2
      breathing at 2.82 atmospheres absolute (U.S.Navy Treatment Table 6 or
      equivalent). Additional treatments (generally no more than one to two) are used
      for residual manifestations until clinical stability; some severe cases may
      require more treatments. Isotonic, glucose-free fluids are recommended for
      prevention and treatment of hypovolemia. An evidence-based review of adjunctive
      therapies is presented.

PMID- 24851554
TI  - Hyperbaric oxygen treatment for air or gas embolism.
AB  - Gas can enter arteries (arterial gas embolism) due to alveolar-capillary
      disruption (caused by pulmonary overpressurization, e.g., breath-hold ascent by
      divers) or veins (venous gas embolism, VGE) as a result of tissue bubble
      formation due to decompression (diving, altitude exposure) or during certain
      surgical procedures where capillary hydrostatic pressure at the incision site is
      sub-atmospheric. Both AGE and VGE can be caused by iatrogenic gas injection. AGE
      usually produces strokelike manifestations, such as impaired consciousness,
      confusion, seizures and focal neurological deficits. Small amounts of VGE are
      often tolerated due to filtration by pulmonary capillaries. However, VGE can
      cause pulmonary edema, cardiac "vapor lock" and AGE due to transpulmonary passage
      or right-to-left shunt through a patent foramen ovale. Intravascular gas can
      cause arterial obstruction or endothelial damage and secondary vasospasm and
      capillary leak. Vascular gas is frequently not visible with radiographic imaging,
      which should not be used to exclude the diagnosis of AGE. Isolated VGE usually
      requires no treatment; AGE treatment is similar to decompression sickness (DCS),
      with first aid oxygen then hyperbaric oxygen. Although cerebral AGE (CAGE) often
      causes intracranial hypertension, animal studies have failed to demonstrate a
      benefit of induced hypocapnia. An evidence-based review of adjunctive therapies
      is presented.

PMID- 24851555
TI  - High-fat diets and decompression stress revisited.

PMID- 24851556
TI  - Response: High-fat diets and decompression stress revisited.

PMID- 24851557
TI  - Antibiotic resistance patterns of Enterococcus spp. isolated from Musca domestica
      and Chrysomya megacephala in ubon Ratchathani.
AB  - BACKGROUND: The housefly Musca domestica and the blowfly Chrysomya megacephala
      are found worldwide and are medically significant as mechanical vectors of
      various pathogens from unsanitary locations to food, resulting in diseases in
      humans. OBJECTIVES: This study aimed to test the antimicrobial activity against
      Enterococcus spp. isolated from M. domestica and C. megacephala by standard disk
      diffusion and minimal inhibitory concentration (MIC), and to study the potential
      of M. domestica and C. megacephala to transfer multi-drug resistant enterococcus
      to humans. MATERIAL AND METHOD: Seven hundred adult flies were collected from
      fresh-food markets, garbage piles, restaurants, school cafeterias, and rice paddy
      fields in Muang Ubon Ratchathani and Warinchamrap in Ubon Ratchathani Province.
      Antimicrobial susceptibility for Enterococcus spp. isolated from adult flies was
      performed by disk diffusion test and minimum inhibitory concentration (MIC)
      determination. RESULTS: One hundred and twenty isolates of Enterococcus spp. were
      taken from 67 M. domestica and 53 C. megacephala. Standard disk diffusion showed
      the Enterococcus spp. isolates exhibited susceptibility to ampilcillin (99.2%),
      chloramphenicol (74.20%), tetracycline (75.0%), vancomycin (50.8%), and
      erythromycin (42.5%). The MICs of antimicrobial agents for all isolates were < or
      = 0.25-8 microg/mL for vancomycin, 1- > 16 microg/mL for tetracycline, 4- > 16
      microg/mL for chloramphenicol, and 0.5-8 microg/mL for ciprofloxacin. CONCLUSION:
      The study demonstrated the potential of M. domestica and C. megacephala to carry
      Enterococcus spp. Nine antimicrobial susceptibility patterns were obtained among
      the 120 enterococci isolates.

PMID- 24851558
TI  - Methicillin-resistant Staphylococcus aureus with reduced susceptibility to
      vancomycin in Sanprasitthiprasong Hospital.
AB  - BACKGROUND: Staphylococcus aureus is a species of bacteria that causes a number
      of diseases and more than 60% of it is presently resistant to methicillin.
      Vancomycin is the drug of choice for the eradication of methicillin-resistant S.
      aureus (MRSA). OBJECTIVE: This study aimed to investigate the susceptibility of
      heterogeneous vancomycin intermediate S. aureus (hVISA) and vancomycin
      intermediate S. aureus (VISA) to vancomycin by standard disk diffusion,
      microbroth dilution, a one-point population assay, and a population analysis
      profile. MATERIAL AND METHOD: Sixty-eight MRSA isolates from patients admitted to
      Sanprasitthiprasong Hospital between November 2010 and November 2011 were tested.
      RESULTS: Standard disk diffusion showed that all the MRSA isolates were
      susceptible to vancomycin. Vancomycin MICs for all isolates were 1-2 microg/mL.
      Only two MRSA isolates (2.9%) were able to grow on brain heart infusion agar
      supplemented with vancomycin 4 microg/mL and were confirmed by a population
      analysis as hVISA. CONCLUSION: This study showed the effect of vancomycin on MRSA
      and the need for early detection and controlled planning.

PMID- 24851559
TI  - Prognostic factors of human papillomavirus genotypes of invasive cervical
      carcinoma: an analytical cross-sectional study in lower north-east Thailand.
AB  - BACKGROUND: Cervical cancer (CXCA) caused by persistent infections by high-risk
      human papillomavirus (HR-HPV) can lead to multi-step carcinogenesis. The best
      management strategy and significant prognosis for cervical cancer patients remain
      unclear. OBJECTIVE: To investigate the associations of the two most common HR
      HPVs with clinical outcomes of progression and recurrence status as well as
      prognosis outcomes of patients. MATERIAL AND METHOD: An analytical cross
      sectional study of patients registered at Ubon Ratchathani Cancer Hospital was
      conducted from 2007 to 2010. Clinical data, histopathological features, and
      clinical outcomes of progression and recurrence status were recorded. HPV type
      specific E6/E7 nested multiplex polymerase chain reaction (NMPCR) was performed
      to identify HR-HPV16 and 18 using extracted deoxyribonucleic acid (DNA) from
      embedded paraffin. Clinical findings and HPV genotypes were analyzed using
      Fisher's exact test. Association studies of crucial factors and HR-HPV genotypes
      were performed using logistic regression analysis (odds ratio [OR]) and 95%
      confidence interval [CI]). A p-value of less than 0.05 was considered
      statistically significant. RESULTS: The study found single HPV16 infection in
      57.3%, single HPV18 in 17.3%, mixed HR-HPV16/18 in 13.1%, and non-HPV16, 18, or
      16/18 in 12.3%. The findings showed significant association among their genotypes
      and histopathological types and grading (p < 0.0001 and p = 0.014). Clinical
      outcomes of progression and recurrence status with increased severity of clinical
      staging were associated significantly (p = 0.001 and p = 0.002). HPV18 type
      specific was shown as a poor prognostic type with its relevance to the severity
      of disease higher than that of HPV16. CONCLUSION AND DISCUSSION: HPV16 and 18
      remain the major type-specifics especially in relation to invasive CXCA,
      requiring further therapeutic vaccination study and proper prognosis. HR-HPV type
      specific is very important during cervical carcinogenesis but other crucial
      contributing factors for prognostic outcomes should be further elucidated.

PMID- 24851560
TI  - Survey of pathogenic Leptospira in rats by polymerase chain reaction in Sisaket
      Province.
AB  - BACKGROUND: Leptospirosis, a zoonotic disease caused by Leptospira, has been a
      health problem in Thailand for several years. It can be transmitted to humans via
      rats' urine, which may contaminate the environment. The prevalence rate of
      Leptospira infection in rats may result in the spread of leptospirosis in humans.
      OBJECTIVE: The present study aimed to determine the prevalence rate of Leptospira
      infection in a total of 87 rats from areas where patients with leptospirosis had
      been reported compared to areas with no reports of leptospirosis in Sisaket
      Province. MATERIAL AND METHOD: DNA samples were isolated from rats' kidneys. The
      polymerase chain reaction (PCR) technique was used for the detection of 16s rRNA
      and LipL32 genes specific to genus and pathogenic Leptospira, respectively.
      RESULTS: In areas where patients with leptospirosis had been reported, 8.7%
      (4/46) of rats were infected with pathogenic Leptospira; no infected rats were
      found in non-endemic areas. CONCLUSION: This indicated the prevalence rate of
      Leptospira infection in rats between endemic and non-endemic areas of human
      leptospirosis. The prevalence rate of Leptospira infection in rats may result in
      the spread of leptospirosis to humans. These results may be of benefit in the
      prevention and/or control of the spread of leptospirosis in humans due to
      Leptospira-infected rats.

PMID- 24851561
TI  - Isolation of Toxocara eggs from flies in Northeast Thailand.
AB  - BACKGROUND: Flies are natural carriers of pathogens and play a considerable role
      in the mechanical transmission of many pathogens, such as viruses, fungi,
      bacteria, and parasites, in various regions of the world. OBJECTIVE: To
      investigate the existence of Toxocara spp. eggs on two types of flies, the
      Oriental latrine fly, Chrysomya megacephala, and the housefly, Musca domestica,
      in Ubon Ratchathani, Northeast Thailand. MATERIAL AND METHOD: Flies were
      collected by the use of sterilized insect sweeping nets at five types of sites,
      fresh-food markets, garbage piles, restaurants, school cafeterias, and paddy
      fields from September 2010 to October 2011. After centrifugation, sediments from
      each fly species were examined for parasites under a light microscope. RESULTS:
      From the analysis of 555 C. megacephala and 439 M. domestica adult samples,
      Toxocara eggs were isolated from only the former species in all sites except for
      the restaurants in the Warinchamrap. No other helminthes and protozoa were found
      on the body surfaces of both fly species. CONCLUSION: The data suggest that C.
      megacephala is more likely to be a potential carrier of Toxocara eggs than M.
      domestica in areas frequented by humans in this region of Thailand.

PMID- 24851562
TI  - Prevalence of helminthic infections and risk factors in villagers of Nanglae Sub
      District, Chiang Rai Province, Thailand.
AB  - The purposes of the present study were to survey the prevalence of helminthic
      infections in people living in Nanglae Sub-District of Chiang Rai Province,
      Thailand from January to March 2013, and to determine factors that correlated
      with these infections. Two hundred and sixty-three fecal samples were examined
      for helminth eggs by the use of Kato's thick smear technique. All data were
      analyzed by descriptive statistics including frequencies, percentages and
      correlations (Odds ratio [OR] and 95% confidence interval [CI]). The percentage
      of overall helminthic infections was 11.8%, comprising 6.1% Taenia spp., 4.5%,
      Ascaris lumbricoides, 0.8%, Strongyloides stercoralis and 0.4% flukes producing
      opisthorchiid-like eggs. In addition, the prevalence of helminthic infection
      correlated significantly with the consumption of raw meat (OR = 2.270, 95% CI =
      1.047-4.923) and raising dogs in the house (OR = 2.444, 95% CI = 1.080-5.534).

PMID- 24851563
TI  - Iron-chelating, free radical scavenging and anti-proliferative activities of
      Azadirachta indica.
AB  - BACKGROUND: Excessive production of reactive oxygen species leads to oxidative
      stress which occurs in various diseases, such as diabetes, cancer,
      neurodegenerative diseases, and secondary iron overload in thalassemia.
      Antioxidants are compounds that inhibit the oxidative processes and delay or
      suppress oxidative stress. Phytochemicals in herbs are interesting sources of
      natural antioxidants with cancer preventive properties. The use of natural
      products is beneficial for the prevention and/or treatment of oxidative stress
      mediated diseases. OBJECTIVE: The study aimed to investigate the antioxidant and
      anti-proliferative properties of ethanolic extract from Azadirachta indica (neem)
      leaves. MATERIAL AND METHOD: Neem leaves were extracted by 80% ethanol (v/v). The
      ethanolic extract was tested for free radical scavenging activity by 2,2'-azino
      bis-3-ethylbenzothiaziline-6-sulfonic acid (ABTS) and for the reduction of the
      power of ferric ion (Fe3+) to ferrousion (Fe2+) by ferric reducing antioxidant
      plasma (FRAP) assay. Furthermore, the ability of iron-binding activity was
      investigated by the spectrophotometry technique. The inhibitory effect on the
      growth of human promyelocytic leukemic cell line (HL-60 cells) was determined by
      MTT assay. RESULTS: The ethanolic extract from neem leaves exhibited free radical
      scavenging activities and reduced the power of ferric ion (Fe3+) to ferrous ion
      (Fe2+) in dose responses. Furthermore, it was able to bind with iron rapidly
      within 5 minutes. Interestingly, this extract inhibited human promyelocytic
      leukemic cell line (HL-60 cells) growth in concentration response (0-500
      microg/ml) for 24 hour treatment. CONCLUSION: The ethanolic extract from neem
      leaves had strong antioxidant activity and an anti-proliferative effect on cancer
      cells.

PMID- 24851565
TI  - Fetal blood sampling in prenatal diagnosis of thalassemia at late pregnancy.
AB  - Fetal blood sampling is a procedure that involves the drawing of a blood sample
      from the umbilical vein of the umbilical cord, which can be performed after 18
      weeks gestation. Fetal blood sampling is a preferable method for prenatal
      diagnosis of thalassemia in second trimester or late pregnancy. Additionally, it
      is suggested to be performed in cases in which mosaicisms are identified by
      amniocentesis or chorionic villus sampling (CVS), areas where DNA analysis is not
      available, and when mutations of the parents are not known. Laboratory steps
      regarding prenatal diagnosis by fetal blood sampling were summarized, including
      the ensuring of fetal origin, determination of red blood cell parameters, fetal
      hemoglobin analysis, and finally fetal DNA analysis. The objective of this review
      is to present an overview of procedures in terms of benefits, laboratory
      interpretations, and some limitations.

PMID- 24851564
TI  - Bactericidal efficacy of alcohol solution in community hospital and health
      centers.
AB  - OBJECTIVE: To evaluate bactericidal efficacy of alcohol solution during actual
      use and typical storage conditions in community hospital and health centers.
      MATERIAL AND METHOD: The alcohol samples were collected immediately after the
      first bottle-opening (day 0) and on day 3, 7, 14, 21 and 30 from 10 stations in
      hospital and community health centers in Pone-na-kaew district, Sakon Nakhon
      province, Thailand, during May-July 2011. Bactericidal efficacy of these samples
      against Staphylococcus epidermidis, Staphylococcus aureus, Escherichia coli,
      Pseudomonas aeruginosa and Klebsiella pneumoniae was evaluated. Ethanol
      concentration was quantified by a gas chromatography method. RESULTS:
      Bactericidal efficacy of the alcohol samples still remained on day 30 with
      ethanol concentration range of 60.91-65.99% v/v. CONCLUSION: This finding should
      be considered as a cost-benefit model for using alcohol solution in community
      hospital and health centers.

PMID- 24851566
TI  - Quartz crystal microbalance biosensors: prospects for point-of-care diagnostics.
AB  - BACKGROUND: A QCM is a label-free and extremely mass-sensitive device, which
      allows the detection of the binding event between trace medical analytes and bio
      receptors on its surface. QCM, the most promising type of biosensors, has
      attracted much interest due to the inherent benefits over other transducers,
      including better sensitivity, ease-of-use, integration with compact analytical
      devices, and economy, and also involving relatively simple technology in its
      production. Thus, they have great potential with regard to point-of-care (POC)
      testing for early detection of diseases. MATERIAL AND METHOD: Retrievable
      articles that related to acoustic type sensing of Pubmed and Science direct
      database were included. Additionally, abstracts presented at Biosensor World
      Congress held between 2008 and 2012 were searching to identify relevant clinical
      trials. RESULTS: All studies demonstrated the opportunity in the use of QCM as a
      novel diagnostic method. Several attempts have been made to construct integrated
      systems that show promising application for POC tests. CONCLUSION: This review
      represents another step to meet challenges, especially in the improved
      minimization and sensitivity of biosensors. As this work continues, new
      bioreceptor and biomarkers emerging from the could make it an ideal candidate for
      cheap POC diagnostic.

PMID- 24851567
TI  - Combined effects of hypertension and diabetes mellitus with stroke among Thais in
      the central region of Thailand: a cross-sectional study.
AB  - OBJECTIVE: To determine associations of individual and combined effects of
      hypertension and diabetes with stroke among Thais aged 55 years and older
      MATERIAL AND METHOD: Cross-sectional data from national screening program for
      metabolic syndrome in Thailand for the year 2010 among participants who lived in
      central region of Thailand were used. The number of participants was 13,268 in
      the analysis. RESULTS: The prevalence of stroke was 0.9%. Associations between
      hypertension and diabetes found among participants who had hypertension only,
      diabetes only, and both hypertension and diabetes were: 8.99 (95% CI 4.63-17.43),
      3.72 (95% CI 1.03-13.37), 10.48 (95% CI 4.54-24.20) among males and 5.16 (95% CI
      2.29-11.53), 6.55 (95% CI 2.19-19.55), and 9.29 (95% CI 3.81-22.68) among
      females, respectively. CONCLUSION: The present study suggested dramatically the
      strong effects of the association of combined hypertension and diabetes with
      stroke. Strengthening health promotion programs for the prevention of
      hypertension, diabetes, especially having both diseases after screening, is
      important among Thai population.

PMID- 24851568
TI  - Factors associated with hepatitis C infection among patients with skin diseases.
AB  - OBJECTIVE: The present study attempted to assess factors associated with positive
      anti-HCV among patients with skin diseases. MATERIAL AND METHOD: A retrospective
      analysis of 3,496 subjects' history profiles from the HCV antibody surveillance
      projects performed from 2000 to 2007. Only 150 subject profiles with skin
      diseases were included in the analysis of factors associated with positive anti
      HCV Patient profiles including socio-demographic parameters, the main risk
      behavior or risk exposure, types of skin diseases, anti-HIV status, and results
      of anti-HCV were analyzed using Chi-square test or Fisher's exact test. RESULTS:
      Results revealed that only 10 from 150 studied patients (6.7%) were positive for
      anti-HCV antibody. Patient profiles including socio-demographic parameters, the
      main risk behavior or risk exposure, types of skin diseases, and anti-HIV status
      among patients with or without anti-HCV were compared and analyzed to assess
      factors associated with positive anti-HCV. It was found that patient's income,
      types of skin disease, and anti-HIV status were significantly associated with
      positive anti-HCV among this group, p = 0.0240, p = 0.0053 and p = 0.0462,
      respectively. CONCLUSION: This analysis found three studied factors including
      patient's income, types of skin disease, and anti-HIV status to be significantly
      associated with HCV infection in patients with skin diseases. However, a large
      scale work should be done to confirm the present study.

PMID- 24851569
TI  - Dengue hemorrhagic fever knowledge, perception, and preventive behavior among
      secondary school students in Bangkok.
AB  - OBJECTIVE: To explore dengue hemorrhagic fever (DHF) knowledge, perception, and
      preventive behavior among secondary school students in Nong-Kheam, Bangkok,
      Thailand. MATERIAL AND METHOD: A cross-sectional descriptive study was conducted
      with 300 students between 12 and 16 years old currently attending secondary
      schools in the Bangkok metropolitan areas using self-administered questionnaires.
      Data were subsequently summarized using descriptive statistics. RESULTS: Only
      18.0% of students had a good level of overall knowledge of DHF but more than half
      had a good level of perception of DHF The results also revealed that only 4.7% of
      students had a good level of preventive behavior and 75.6% required improvement.
      CONCLUSION: The levels of knowledge, perception, and preventive behavior were
      low. Health education programs should be continued and intensified with emphasis
      on improving the knowledge of students on prevention and control practices.

PMID- 24851570
TI  - Effect of oat consumption on lipid profiles in hypercholesterolemic adults.
AB  - BACKGROUND: Hypercholesterolemia is a strong risk factor in cardiovascular
      disease. Oat (Avena sativa L.) beta-glucan, the soluble fiber in oat, has been
      known to reduce blood cholesterol levels considerably. However, the effect of oat
      soluble fiber in the Thai population is unknown. OBJECTIVE: To determine the
      effect of oat consumption on serum lipid profiles in Thai hypercholesterolemic
      adults. MATERIAL AND METHOD: The present study was a randomized, crossover
      design. Twenty-four hypercholesterolemic adults, male and female aged 30-60
      years, were randomly assigned into two groups of twelve each. Group 1 consumed 70
      g (3 g beta-glucan) of oatmeal daily through the first 4-week intervention, and
      then switched to 70 g rice porridge (control product) daily for the next 4-week
      intervention. Group 2 consumed rice porridge first and then oatmeal. Before and
      after each intervention period, lipid profiles including total cholesterol (TC),
      triglycerides (TG), high density lipoprotein cholesterol (HDL-C), and low density
      lipoprotein cholesterol (LDL-C) of all subjects were measured. RESULTS: Following
      daily oat consumption, total cholesterol and LDL-cholesterol levels were
      significantly lower than baseline levels and lower than the levels observed with
      rice consumption. Oat consumption reduced total cholesterol by 5% and LDL
      cholesterol by 10% from baseline levels. In addition, mean and percent changes
      were significantly different from the levels after consuming rice porridge (p <
      0.05). CONCLUSION: Oatmeal reduced serum total cholesterol and LDL-cholesterol
      levels in hypercholesterolemic Thai adults. Hence, oat consumption is a
      reasonable recommendation for Thai individuals with hyperlipidemia.

PMID- 24851571
TI  - Prevalence and factors associated with metabolic syndrome among a group of Thai
      working population: a cross sectional study.
AB  - OBJECTIVE: To determine prevalence and factors associated with metabolic syndrome
      (MetS) among employees of the Electricity Generating Authority of Thailand based
      in Bangkok. MATERIAL AND METHOD: The present study was conducted among 2,544
      participants (1,875 men, 669 women) enrolled in the cohort study of Faculty of
      Medicine, Ramathibodi Hospital. Baseline cross sectional data in 2009 was
      analyzed. The MetS was defined using NCEP ATP III criteria. Odds ratios (OR) and
      95% confidence interval (95% CI) stratified by gender were computed. RESULTS:
      Overall prevalence of metabolic syndrome was 16.6%, 18.2% in males and 10.3% in
      females. More than half of the participants had a low intensity of physical
      activity. Significant non-modified factors associated with MetS among males were
      increased age (OR = 1.02; borderline 95% CI 1.00-1.04), levels of education were
      bachelor degree and lower compared with higher than bachelor degree (OR = 1.87;
      95% CI 1.20-2.91 and OR = 2.28; 95% CI 1.32-3.93), working in a middle and lower
      type of job (OR = 1.44; 95% CI 1.01-2.05, OR = 2.08; 95% CI 0.98-4.40) compared
      with a high-end type of job. For females, significant factors associated with
      MetS were increased age (OR = 1.08; 95%CI 1.02-1.15), having middle income
      compared with high income (OR = 3.01; 95% CI 1.28-7.06). CONCLUSION: Modified
      risk factor in low physical activity should be managed by increased intensity of
      physical activity among participants in a low and middle type of job and income
      to reduce cardiovascular risk.

PMID- 24851572
TI  - Perception and knowledge on health risks by waterpipe tobacco-smoking tourists in
      a night spot of Bangkok, Thailand.
AB  - OBJECTIVE: To identify the perception level, and knowledge level of health risks
      due to waterpipe tobacco smoking, and knowledge about prohibition of waterpipe
      tobacco smoking, of foreign tourists in Thailand. MATERIAL AND METHOD: This is a
      descriptive cross-sectional study, carried out among foreign tourists in
      nightspots on Khao San Road area of Bangkok. Structured interview questionnaire
      was the data collection instrument for 176 convenience-sampling. RESULTS: More
      than half (52.3%) of the foreign tourists had a poor level of perception about
      waterpipe smoking. Majority of foreign tourists (75.5%) had low level of
      knowledge on the health risks. More than 50% didn't know about the illegal status
      of waterpipe smoking in Thailand. Chi-square analysis showed that the region
      where tourists reside was statistically associated with the perception level
      regarding waterpipe smoking. Age of waterpipe smoking initiation was associated
      with the region and gender Age of tourists was associated with the knowledge on
      prohibition of waterpipe smoking. CONCLUSION: Raising awareness among foreign
      tourists through media advocacy about the rules and regulations regarding
      waterpipe smoking is necessary to support tobacco control policy. Strict
      enforcement of the existing law on prohibiting waterpipe smoking should be
      implemented, Authorities should inform owners/managers of waterpipe, tobacco
      smoking prohibition, and require them to put up prohibition signs in their
      establishments, in both Thai and English languages.

PMID- 24851573
TI  - Computer assisted instruction on "learning nutrition flags for deaf 5th grade and
      6th grad students": effectiveness of instruction.
AB  - OBJECTIVE: Deaf students are of a number of under privilege group for whom there
      are limited resources for their use, related to health including nutrition. The
      purpose of this research was to create computer-assisted instruction for
      "nutrition flags" for 5 and 6th grade students. The content of nutrition included
      the concept of a healthy balance diets and portion sizes of each food group.
      MATERIAL AND METHOD: The content and pictures for computer-assisted instruction
      came from existing curriculum, and focused on nutritional content. The contents
      in this instruction were divided into three units according to students' learning
      capacity. The story boards were developed by staff including nutritionists, Thai
      sign language interpreters, and deaf students. Then, the contents and nutrition
      vocabulary were translated into Thai sign language. After recording the sign
      language on video, this material was merged with the contents and converted into
      a computer program. The computer assisted instruction was tested with students
      from Nakon Pathom School for the Deaf The first trial was conducted with three
      students, the second with five students, and the third with 15 students during
      the academic year 2009. The computer- assisted instruction was revised until it
      met the standard criteria of 80/80. Effectiveness testing was carried out with 36
      students for five consecutive days. On the first day, the pre-test was completed,
      and on days 2-4, the students performed self-study and completed the exercises
      for units 1-3, with 50 minutes spent on each unit. The post-test was completed on
      the last day. The study was conducted during the 2010 academic year Data analysis
      was performed using the t-test. RESULTS AND CONCLUSION: The results showed an
      effectiveness of 81.85/82.22, which was higher than the standard criteria of
      80/80. The post-test average score was higher than the pre-test average score
      with a statistical significance level at p < 0.0001. Suggestions for instruction
      for the deaf are that the length of the instruction in each unit should be no
      longer than 30 minutes and the sign language window should be large because this
      mode of communication relies on sight.

PMID- 24851574
TI  - The life experiences of Thai women and smoking: a phenomenological study.
AB  - OBJECTIVE: Exploring and understanding the live experiences of women smokers as
      well as the conditions and the family/social context of Thai society. MATERIAL
      AND METHOD: A phenomenological approach was used and conducted from July 2011 to
      April 2012. The informants were 25 Thai women smokers in Bangkok and peripheral
      areas. Data were collected from focus group discussions and indepth interviews
      and was analyzed using Diekelmann and Love thematic analysis. RESULTS: The
      informants ranged in age from 14 to 66 years. The highest education level was a
      Vocational Certificate and the lowest level was a primary education (Grade 4).
      The youngest began smoking at 12 years. The average duration of smoking behavior
      was 22.3 years; the longest of smoking duration was 52 years. They smoked 2.4
      packs of cigarettes per day on average, 6 packs per day at the maximum. Within a
      family setting, the highest number of people smoking and living in the same
      household was 13 persons. Five themes were identified as follows: 1) the starting
      point of smoking:-the family environment triggers smoking; 2) the meaning of
      smoking:-smoking means 'cigarettes are like friends ', 3) femininity and
      smoking.:-smoking is an individual right and is not illegal; 4) smoking and
      health:-smoking-health linkage is not an immediate issue as the informants did
      not suffer from any serious illness; and 5) view on/intention to stop smoking:
      the permanent cessation of smoking was not possible due to the current
      environment in which their friends or family members still smoked, and because
      some also chose to reduce their stress by smoking. CONCLUSION: Family environment
      and peer group influenced the informants smoking behavior Children see their
      grandmother mother or elder sister smoke, so smoking is perceived as normal
      behavior among women as well. Most of them had chosen cigarette smoking as a way
      to relieve themselves from stressful environments.

PMID- 24851575
TI  - Health effects of people living close to a petrochemical industrial estate in
      Thailand.
AB  - OBJECTIVE: An acute health effect of people living near the petrochemical
      industrial estate in Thailand was assessed using a panel study design. MATERIAL
      AND METHOD: The populations in communities near the petrochemical industrial
      estates were recruited. The daily air pollutant concentrations, daily percentage
      of respiratory and other health symptoms reported were collected for 63 days. The
      effect of air pollutants to reported symptoms of people were estimated by
      adjusted odds ratios and 95% confidence interval using binary logistic
      regression. RESULTS: The significant associations were found with the adjusted
      odds ratios of 38.01 for wheezing, 18.63 for shortness of breath, 4.30 for eye
      irritation and 3.58 for dizziness for total volatile organic compounds (Total
      VOCs). The adjusted odds ratio for carbon monoxide (CO2) was 7.71 for cough, 4.55
      for eye irritation and 3.53 for weakness and the adjusted odds ratio for ozone
      (O3) was 1.02 for nose congestion, sore throat and 1.05 for phlegm. CONCLUSION:
      The results showed that the people living near petrochemical industrial estate
      had acute adverse health effects, shortness of breath, eye irritation, dizziness,
      cough, nose congestion, sore throat, phlegm and weakness from exposure to
      industrial air pollutants.

PMID- 24851576
TI  - Health risk assessment of volatile organic compounds in a high risk group
      surrounding Map Ta Phut industrial estate, Rayong Province.
AB  - OBJECTIVE: The health risks of a high-risk group, surrounding Map Ta Phut
      industrial estate, Rayong, which may be exposed to VOCs through inhalation of
      contaminated air and dermal contact of contaminated water were assessed. MATERIAL
      AND METHOD: The health risk was assessed for 19 subjects categorized as children,
      adult and elderly from Ban plong and Nongfab communities following the US
      Environmental Protection Agency (EPA) method. The VOC concentrations in ambient
      air and ground water were monitored by Pollution Control Department (PCD),
      Ministry of Natural Resources and Environment to represent average VOC exposure
      of subjects. RESULTS: The lifetime cancer risk of VOCs exposure from inhalation
      and dermal contact with ground water were 1.32 x 10(-7)-5.21 x 10(6) for elderly
      1.18 x 10(-7)-6.20 x 10(-6)for adult and 8.93 x 10(-7)-5.93 x 10(-6) for
      children. For non-cancer risk, the hazard index was 0.44 for elderly, 0.38-0.42
      for adult and 0.55 for children. CONCLUSION: The lifetime cancer risk of the high
      risk group living near Map Ta Phut industrial estate was in acceptable range for
      elderly, adult and children. For non-cancer risk, it is also acceptable.

PMID- 24851577
TI  - Assessment of occupational exposure to malathion and bifenthrin in mosquito
      control sprayers through dermal contact.
AB  - OBJECTIVE: To assess occupational exposure of malathion and bifenthrin
      concentrations by dermal contact and urinary 3-(2-chloro-3, 3, 3-trifluoro-1
      propenyl)-2, 2-dimethyl-cyclopropanecarboxylic (TFP) acid, health symptoms
      developed and the relationship between bifenthrin concentrations and TFP acid in
      urine of the mosquito control sprayers. MATERIAL AND METHOD: The aerosols of
      these two pesticides were collected using 100 cm2 cotton patches attached on the
      skin of upper legs of 54 volunteer of mosquito control sprayers. Their urine
      samples were also collected before and after application. RESULTS: These subjects
      exposed to average malathion and bifenthrin concentrations of 0.18 and 0.32
      microg/cm2, respectively After application, the average concentration of urinary
      TFP acid in the sprayers was 39.22 +/- 0.77 mg/g creatinine ranging from 0.58 to
      261.19 mg/g creatinine. A significant difference was found between urinary TFP
      acid levels before and after application (p < 0.001) but the bifenthrin
      concentrations through dermal contact and urinary TFP acid levels were not
      significantly correlated (p > 0.05). CONCLUSION: The mosquito control sprayers
      had dermal contact with smoke of malathion and bifenthrin and some sprayers
      developed health symptoms after exposure. They should use protective clothing
      made ofplastic, nylon or polyester to protect sprayers from skin contact.

PMID- 24851578
TI  - Factors influencing happiness of the grandmothers raising grandchildren in rural
      areas of Northern Thailand.
AB  - OBJECTIVE: To study the factors influencing happiness of grandmothers raising
      grandchildren in the rural areas of Northern Thailand. MATERIAL AND METHOD: Cross
      sectional survey research was conducted among 400 grandmothers, aged 50-79 years,
      who raised their grandchildren in the rural areas of Northern Thailand.
      Participants were selected by cluster sampling. Data were collected through a
      structured interview from April to July 2009 and analyzed by frequency,
      percentage, Pearson product moment correlation coefficient, and Multiple
      regression analysis. RESULTS: Nearly half (46.8%) of grandmothers raising
      grandchildren had high level of happiness, followed by moderate level (40.4%) and
      low level (12.8%). The factors, which significantly influenced the happiness of
      the grandmothers, were self-esteem, social support, and family relationships (p
      value < 0.05). In addition, self-esteem, social support, and family relationships
      could significantly predict happiness of the grandmothers by 48.1%. Self-esteem
      had the highest predictive power of happiness among grandmothers. CONCLUSION: The
      factors influencing happiness of grandmothers raising grandchildren were self
      esteem, social support, and family relationships. To promote happiness of
      grandmothers, responsible organizations should establish activities that enhance
      the grandmother's self-esteem, provide sufficient social support, and promote
      good family relationships.

PMID- 24851579
TI  - Factors influencing family planning practice among reproductive age married women
      in Hlaing Township, Myanmar.
AB  - OBJECTIVE: To study the factors that influence the family planning practice among
      married, reproductive age women in Hlaing Township, Myanmar. MATERIAL AND METHOD:
      Cross-sectional survey research was conducted among 284 married, reproductive age
      women using stratified random sampling. The data were collected through
      questionnaire interviews during February and March 2012 and analyzed by
      frequency, percentage, Chi-square test, and multiple logistic regression.
      RESULTS: The proportion of families practicing family planning was 74.7%,
      contraceptive injection being the most commonly used method. The factors
      influencing family planning practice were attitude towards family planning, 24
      hour availability of family planning services, health worker support, and partner
      and friends support. The women with a positive attitude toward family planning
      practiced family planning 3.7 times more than women who had a negative attitude.
      If family planning services were available for 24 hours, then women would
      practice 3.4 times more than if they were not available for 24 hours. When women
      got fair to good support from health workers, they practiced 15.0 times more on
      family planning and 4.3 times more who got fair to good support from partners and
      friends than women who got low support. CONCLUSION: The factors influencing
      family planning practice of married, reproductive age women were attitude toward
      family planning, 24-hour availability of family planning services, health worker
      support, and partner and friends support. The findings suggest that empowerment
      of health workers, training of volunteers, pharmacists and contraceptive drug
      providers, encouraging inter-spousal communication, and peer support, as well as
      an integrated approach to primary health care in order to target different
      populations to change women's attitudes on family planning, could increase family
      planning practice among Myanmar women.

PMID- 24851580
TI  - Condom use among male migrant workers in dry zone, Myanmar.
AB  - OBJECTIVE: To study the factors associated with condom use among male Myanmar
      migrant workers in Pakokku, Myanmar MATERIAL AND METHOD: This cross-sectional
      study used two stages cluster sampling with probability proportional to size
      (PPS) method to collect samples. During 1-14 February 2010, 324 male Myanmar
      migrant workers between 18 and 60 years of age were asked to complete face-to
      face structured interview on knowledge, perception, cues to action, peer
      influence and sexual behaviors. Data were analyzed by descriptive statistics, Chi
      square test and Fishers exact test. RESULTS: Results revealed that 71.0 percent
      of respondents were under young and middle adult age and 66.7 percent were
      married. It showed that 11.1 percent of the respondents used condom regularly
      with spouse or girlfriends or sex workers during the past year There were
      associations between age (p = 0.006), marital status (p < 0.001), educational
      level (p = 0.014), monthly income (p = 0.015), level of knowledge on HIV/AIDS (p
      = 0.017), perceived susceptibility of getting HIV/ AIDS (p = 0.024) and condom
      use. No associations were noted between occupation, duration of career; duration
      of each trip, perceived severity, perceived benefit, perceived barrier, cues to
      action, peer influence and condom use. CONCLUSION: With low proportion of regular
      condom use among study group, behavior change, communication interventions and
      strengthening of the 100.0% Targeted Condom Promotion Project are recommended to
      promote perception and knowledge about HIV/AIDS and condom use among male migrant
      workers.

PMID- 24851581
TI  - Spatial analysis of social determinants for tuberculosis in Thailand.
AB  - OBJECTIVE: The present study aimed to investigate the association between social
      factors and spatial risk of TB in Thailand. MATERIAL AND METHOD: Ecological study
      and spatial statistics were employed to examine effects of social factors on age
      standardized morbidity ratios of TB (SMR) in 76 provinces in Thailand during 2006
      2009. RESULTS: The autoregressive model reveals similarity of TB risk in proximal
      areas (Moran's I = 0.612; p < 0.05). After adjusting for HIV epidemic and spatial
      autocorrelation (rho = 0.581, p < 0.001), a spatial autoregressive model revealed
      significant relationship of unemployment rate (beta = 0.073) and household income
      (beta = 0.134) to spatial risk of TB with variance of explanation 55%.
      CONCLUSION: The present study indicated the area at risk of TB is in areas with
      high employment rate and household income, which are specific characteristics of
      an urban area. Therefore, in urban areas that are vulnerable to TB transmission,
      a development of specific TB surveillance and prevention and control programs is
      need.

PMID- 24851582
TI  - An effect of walking exercise applying the theory of planned behavior in people
      at risk of hypertension.
AB  - OBJECTIVE: To investigate an effectiveness of walking exercise program applying
      the Theory of Planned Behavior in people at risk of hypertension in Samut Sakorn
      province. MATERIAL AND METHOD: The present study is a quasi-experimental
      research. The inclusion criteria were people aged 35-59 years old, systolic blood
      pressure 120-139 mmHg, and diastolic blood pressure 80-89 mmHg. Participants were
      randomly selected into the experimental group (n = 34) and the comparison group
      (n = 34). The experimental group received activities including health
      information, benefits of walking exercise, group discussion in exercise barriers,
      modeling and experience exchange, walking exercise practice, and practice on
      using walking monitoring booklet at the baseline and the 2nd week, whereas the
      comparison group received only health information and the booklet practice at the
      beginning of the intervention. Data were collected by self-administered
      questionnaires at the baseline, 2nd week, and 6th week. Statistical analysis was
      performed using Chi-square, Independent t-test, and repeated measures ANOVA.
      RESULTS: The experimental group made significant improvements in attitude towards
      walking exercise, perceived behavior control, subjective norm, walking exercise
      intention, and walking exercise over time (p < 0.05). However, no statistically
      significant differences between the experimental and the comparison groups were
      found in subjective norm, systolic and diastolic blood pressure from baseline to
      the 6th week. The experimental group had a significant higher mean difference
      score of attitude towards walking exercise, perceived behavior control, walking
      exercise intention, walking exercise, weight, and BMI compared to those in the
      comparison group (p < 0.05). Subjective norm scores in the experimental group
      were more likely to increase from baseline to the 6th week, but not a significant
      difference. CONCLUSION: Walking exercise programs applying the Theory of Planned
      Behavior should be recommended in people at risk of hypertension. Health
      professionals should also be motivated to practice with this program.

PMID- 24851583
TI  - Self-efficacy, decisional balance and stages of change on dietary practices among
      metabolic syndrome persons, Uthai Thani Province.
AB  - OBJECTIVE: To determine factors related to stages of change regarding dietary
      intake of persons with metabolic syndrome in Uthai Thani. MATERIAL AND METHOD:
      Five hundred metabolic syndrome persons were randomly selected using a three
      stage sampling method and voluntarily responded to a validated, self-administered
      questionnaire. RESULTS: Majority of the respondents (36.4%) had dietary practices
      in the pre-contemplation stage while only 17.4 percent of them were in the action
      and maintenance stage. Perceived self-efficacy, pros, and cons of decisional
      balance for dietary intake had statistically positive association with the stages
      of change (Somers' d value = 0.21, 0.29, and 0.09 with p < 0.01, < 0.01, and
      0.015 respectively). CONCLUSION: Perceived self-efficacy, pros, and cons of
      decisional balance are related to stages of change regarding dietary intake of
      persons with metabolic syndrome. Therefore, perceived self-efficacy, pros for
      positive and cons for negative dietary intake should be emphasized to elevate
      food consumption practices of the metabolic syndrome persons from pre
      contemplation to action and maintenance stage.

PMID- 24851584
TI  - Quality of life among women living with HIV/AIDS in Yangon, Myanmar.
AB  - OBJECTIVE: Women living with HIV/AIDS have many problems, especially in their
      quality of life. Although they receive ARTI they still experience stress and are
      discriminated against in their communities. Stigmatization, social support and
      other individual factors such as disease progression, economic status and gender
      role are determinants of quality of life among women living with HIV/AIDS. This
      cross sectional study was aimed to measure the quality of life among women living
      with HIV/AIDS in Yangon and to identify the factors that are able to predict it.
      MATERIAL AND METHOD: 172 women living with HIV/AIDS, were included in the present
      study and were interviewed by using questionnaires. The WHOQOL-BREFform with 26
      items was usedfor assessing the quality of life, then t-test and regression
      analysis was used for statistical analysis. RESULTS AND CONCLUSION: Overall
      quality of life all domain scores were presented with transformed score (0 to 100
      scale) for comparison, and the mean score was 79.7. Physical domain was the
      highest with a score of 58.19, social domain was 56.49, psychological domain was
      48.54 and environmental domain was 46.84. A total of 64.5% had experienced a low
      level of perceived stigma, and only 0.6% experienced a high level of perceived
      stigma. Only 7% had good social support and 22.1% had low support. Social
      support, last CD4 count, family income per month, age, stigma and duration of
      treatment were determined as the significant predictors on quality of life after
      controlling for other factors. The factors could explain 22% of the variation in
      quality of life. In the absence of good social networks, peer group support,
      family involvement and support, reduction of stigma through multi-sectored
      approaches, women with HIV/AIDS will continue to suffer poor quality of life,
      less enjoyment and poor life satisfaction.

PMID- 24851585
TI  - Why do the street children of Kathmandu do not want to live in rehabilitation
      homes?
AB  - OBJECTIVE: The general objective of the present study was to identify the factors
      associated with street children's decision to live in Rehabilitation homes.
      MATERIAL AND METHOD: It was a cross sectional study with 118 respondents. Data
      were collected by snowball sampling using constructed questionnaire and focus
      group discussion was also done for in-depth understanding. Descriptive, Chi
      square and multivariate logistic regression study was carried out based on the
      PRECEDE model to analyze the data. RESULTS: Lack of care (p-value = 0.005),
      attitude of the respondents (p-value = 0.004), strict rules within the
      organizations (p-value = 0.025) and resilience of the respondents (p-value =
      0.001) were significantly associated with the decision of the children to live in
      rehabilitation homes. The results of the multivariate logistic regression
      confirmed that children who were weakly resilient were 4.5 times more likely (OR
      = 4.54, 95% CI: 1.28-16.06), moderately resilient were 4 times more likely to
      live in rehabilitation homes (OR = 4.24, 95% CI: 1.53-11.68), than strong
      resilient. Children with favorable attitude were 16 times more likely to join
      rehabilitation homes (OR = 16.30, 95% CI: 1.78-149.10) than those favorable ones.
      CONCLUSION: The results showed that the children had open access to
      rehabilitation programs and services, but they had an unfavorable attitude
      towards the organizations. Most of the children were resilient and well aware of
      their situation. Organizations were mostly seen by these children as a means of
      support, but not the only option to better their life, indicating that programs
      and services should be planned accordingly and should not focus on
      institutionalizing them as the only solution.

PMID- 24851586
TI  - Development of natural helper characteristic scale (NHCS): an instrument for
      identifying natural helpers for health area in Thai context.
AB  - BACKGROUND: Volunteerism in health through cadres of village health volunteers
      (VHV) has been common since the "health for all" campaign. At present, with
      political support, the VHV receives monthly financial support, and this creates a
      conflict of interest and competition among the VHV groups. Therefore, a tool to
      identify the VHV who has natural helper characteristics, a voluntary mind set and
      a readiness to help is needed. OBJECTIVE: The purpose of the present study was to
      develop and test the quality of the natural helper characteristic scale (NHCS).
      MATERIAL AND METHOD: The present study used a multi-methods design to identify
      natural helper characteristic constructs in the Thai public health context by
      interviewing community leaders and public health professionals who have
      experience in working with natural helpers successfully. Suggested constructs
      have been validated with key informants using telephone interview to confirm the
      common constructs before reconfirmation with factor analysis and reliability
      statistical test. RESULTS: Qualitative data indicated 3 constructs is commonly
      found and statistically tested by exploratory factor analysis revealed a 30-item
      with a five-factor solution (altruism, role recognition, openness to new
      experiences, family readiness, and social acceptance) that accounted for 62.24%
      of the variance. The finding of confirmatory factor analysis indicated that the 5
      factor model with 24 items demonstrated acceptable fit indicated a good fit to
      the data (2 = 439.91; df = 217 (p < 0.001); chi2/ df = 2.02; RMSEA = 0.05; GFI =
      0.90; and, CFI = 0.96). Cronbach's alpha coefficients of the total scale's
      Cronbach's alpha was 0.94. CONCLUSION: The NHCS demonstrated evidence of the
      content and construct validity, and adequate internal consistency reliability.
      The NHCS can be used for identifying natural helpers in working for the health
      programs.

PMID- 24851587
TI  - Sodium intake and socio-demographic determinants of the non-compliance with daily
      sodium intake recommendations: Thai NHES IV.
AB  - OBJECTIVE: To estimate daily intake of sodium and examine the relation of socio
      demographic factors with sodium intake exceeding the recommendations. MATERIAL
      AND METHOD: Data from the Thai National Health Examination Survey IV (NHES IV)
      conducted during 2008-2009 were used. The 24-hour-dietary-recall data were
      available for a subsample of 10% of the total participants. All food and beverage
      data were analyzed for amount of total daily sodium intake for each person. In
      statistical analyses, descriptive statistics were employed to describe
      participants' characteristics, quantities of dietary sodium and percentages of
      participants noncompliant with daily sodium intake recommendations. Logistic
      regression was used to examine socio-demographic determinants of sodium intake
      exceeding the recommendations. RESULTS: 2,969 participants participated in this
      study. Sodium intake varied by socio-demographics. Percentages of participants
      non-compliant with sodium intake recommendations ranged from 75.3 (> or = 1,500
      mg) to 52.0 (> or = 2,400 mg) for those aged < 16 years and from 86.3 (> or =
      1,500 mg) to 67.6 (2,400 mg) for those aged > or = 16 years. In the younger
      group, age and region were key determinants of consuming sodium exceeding all
      recommendations. Having family income between 5,000 and < 10,000 baht/month was
      significantly associated with sodium intake exceeding recommendation targets. In
      the older group, being female and increasing age reduced a risk of non-compliance
      with some recommendations; oppositely, region and residential area participants
      lived significantly, increased non-compliant risk. CONCLUSION: Most participants
      consumed dietary sodium exceeding current recommendations. Effective programs to
      reduce sodium intake in Thais are critical.

PMID- 24851588
TI  - Not chewing food among the Thai elderly with complete denture.
AB  - OBJECTIVE: The study aims to investigate the use of a complete denture in terms
      of not chewing food and determining the strength of association between not
      chewing food and several potential risk factors among the Thai elderly. MATERIAL
      AND METHOD: Under the support of the "Khao Aroi" or "Delicious Rice" or "Dental
      Implant" Project of Institute of Dentistry, Department of Medical Services,
      Ministry of Public Health, and in co-operation with the Ministry of Science and
      Technology during 2007-2011, a cross-sectional survey by multi-stage cluster
      sampling was conducted in 2008, in 21 provinces, 87 hospitals, with 2,676 Thai
      elderly. The sample was drawn from a sampling frame of 58,043 target Thai people
      aged 60 years and over under the Dental Prosthesis Service Campaign (DPSC)
      project during 2005 and 2007. All Thai elderly, who received a complete denture
      from the DPSC project at least three months prior were surveyed from May to
      October 2008 through questionnaires. Data were analyzed by a set of descriptive
      analyses and binary logistic regression models. RESULTS: Not chewing food among
      the Thai elderly, after receiving a complete denture, was 12.5%, quite a bit more
      effective than ordinary work. Nontaluck found 38% for the proportion not wearing
      dentures in the 30-baht health care program. This finding is confirmed by the
      work of Dalodom et al that the use of dentures by Thai elderly was 93% in the
      DPSC project. The important risk factors that influenced not to chew food were
      satisfaction with dentures, patients satisfaction with the denture fitting and
      care, while controlling the amount of dentures, respectively. CONCLUSION:
      Satisfaction of patients with their dentures, good oral health care in fitting
      denture work, and good communication between dentists and patients are important
      keys affecting the use of dentures.

PMID- 24851589
TI  - Parents' perceptions of child abuse and child discipline in Bangkok, Thailand.
AB  - BACKGROUND: Violation of a child's right to protection is an issue for children
      all over the world. In Thailand, the greatest barrier to intervening in child
      abuse issues is the lack of awareness and the positive attitudes and beliefs on
      using violence as a way to discipline children. The incongruent definition used
      amongst Thai society and relevant sectors, causes incidences to be under reported
      and an obstacle to child survival and development. OBJECTIVE: The present study
      is a qualitative study and aims to explore the perceptions of child abuse and
      child discipline definitions amongst parents in the Bangkok Metropolitan Area in
      order to extend broader knowledge for interpretation, definitions and to
      differentiate the line between child abuse and child discipline. MATERIAL AND
      METHOD: Focus group discussions were used as the primary data collection method
      and content analysis was applied as the data analysis. RESULTS: The results
      produced two categories of parents' perceptions regarding child abuse and
      discipline. First, was the perception of the causes of child punishment and child
      discipline, and second was the meaning and difference between child abuse and
      child discipline. CONCLUSION: The study results would be beneficial for policy
      makers, health and related sectors to understand the meaning of the terms used
      amongst family members in order to apply and promote child protection strategies
      in culturally appropriate

PMID- 24851590
TI  - Carbon balance in municipal solid waste management--a case study of Nonthaburi
      municipality, Thailand.
AB  - OBJECTIVE: This research aimed to investigate the carbon equivalences associated
      with the unit processes of municipal solid waste management (MSWM) in Nonthaburi
      municipality. In addition, factors affecting MSWM's carbon-related activities
      were determined to find the reduction potential of carbon emissions into the
      atmosphere. MATERIAL AND METHOD: Afield survey was conducted to quantify the
      amount of resources used in MSWM. Then, they were evaluated in terms of carbon
      equivalences occurring in the process scheme and categorized into carbon
      emissions, fixation and reduction,following a carbon-balanced model. RESULTS:
      From carbon balance analysis of the base-line-scenario MSWM, the carbon emissions
      were found to be -2,374.56 MTCE/y, resulting in the average carbon unit of-22.98
      kg CE/ton solid waste. The negative sign indicates a carbon reduction, instead of
      an emission,from this MSWM practice, which helps to reduce the concentration of
      carbon dioxide in the atmosphere. CONCLUSION: The results of the model reveal
      that the highest contribution to carbon reduction potential in MSWM is recycling.
      Accordingly, it is strongly recommended that a policy promoting reuse, recovery,
      and recycling be pursued in every step of MSWM to assist in, not only extending
      landfill service life span, but also alleviating the increasing global warming
      problems.

PMID- 24851591
TI  - Determinant factors of life expectancy at birth in the European union countries.
AB  - The main aim of this article is to explore determinants of life expectancy at
      birth among 28 European Union countries. Selected variables namely, gross
      domestic product (GDP) growth rate, population growth rate, level of education
      attained, education enrolment, GDP per capita and life expectancy have been
      considered for abovementioned countries in the period from 2001 to 2011 on a
      yearly basis by applying panel data analyses approach. Obtained results reveal
      that GDP per capita and attained education level together explain between 72.6%
      and 82.6% of differences in life expectancy at birth (depending on year of
      observation).

PMID- 24851593
TI  - Life satisfaction and school performance of children exposed to classic and cyber
      peer bullying.
AB  - This paper analyses the relationship between the exposure of school children to
      various forms of peer bullying (classic/cyber) and their life satisfaction in the
      domain of school, family, friends and school performance. The sample included 562
      children from rural and urban areas of Croatia who were attending the seventh and
      the eighth grade of primary school. Results show that children were more often
      exposed to classic forms of peer bullying, especially verbal, and then physical
      bullying. On the other hand, cyber bullying most often comprises harassment in
      forums, blogs, chats or social networks, then on the web, by e-mail and mobile
      phone. Almost half of the examinees knew the identity of the bully, while a
      minority believes that bullies are the same ones who also physically abuse them
      at school. We found that children exposed to all forms of both classic and cyber
      bullying, unlike their peers who do not have such experience, show less
      satisfaction with friends, while those exposed to physical and cyber bullying
      show dissatisfaction with their family, too. However no statistically significant
      difference was found in their satisfaction with school. Children exposed to
      physical bullying showed poorer school performance, poorer achievement in
      Croatian and math, while children exposed to verbal and cyber bullying and
      children who were not exposed to such forms of bullying showed no differences in
      their school achievement.

PMID- 24851592
TI  - Mixed feelings about the diagnosis of type 2 diabetes mellitus: a consequence of
      adjusting to health related quality of life.
AB  - This study aims to explore patients' reactions to the diagnosis of type 2
      diabetes mellitus (T2DM) and their health related quality of life. We adopted a
      qualitative exploratory study design using a thematic analysis. Twelve patients
      with T2DM for more than a 2-year duration were interviewed using a semi
      structured interview guide. Both purposive and theoretical samplings were used
      for data collection. The in-depth interviews were audio-taped and transcribed
      verbatim, followed by line-by-line coding and constant comparison to identify the
      themes. Data management was facilitated using Nvivo 10. Patients shared their
      mixed feelings about the diagnosis of T2DM. Six domains of quality of life
      emerged from these interviews, namely physical and social functioning, work
      function and social obligations, dietary freedom and conforming to treatment
      standard. Diabetes management needs to take these themes and patients' feelings
      associated with their quality of life into consideration.

PMID- 24851594
TI  - Sexual behaviour and condom use as a protection against sexually transmitted
      infections in student population.
AB  - The aim of the study was to determine the differences in sexual behaviour and
      condom use as a protection against sexually transmitted infections (STI) between
      the first-year and the last-year students. Data were collected by filling
      anonymous and consented questionnaire in June of 2011 at University of Josip
      Juraj Strossmayer in Osijek, Croatia. Out of 857 students in the planned sample,
      462 (53.9%) filled out the questionnaire, and 353/462 (76.4%) were sexually
      active. Data from sexually active students were processed and statistically
      significant results between first-year and the last-year students were presented.
      Studied sample consisted of 192/353 (54.4%) first-year students and 161/353
      (45.6%) last-year students. Average age of sexual initiation for the first-year
      students was 17.28 +/- 1.29 years, a for the last-year students 18.45 +/- 2.14
      years, and the difference is significant (Man-Whitney test = 10335.00, p < 0.01).
      First-year students have lower number of sexual partners (chi2 = 28.005, p <
      0.01), during relationship they had lower number of intercourses with the third
      person (2 = 17.947, p < 0.01), and feel that lower number of their friends were
      already sexually active at the time of their own sexual initiation (chi2 =
      18.350, p < 0.01). First-year students more often inform their partners about
      existing or previous STI (chi2 = 14.476, p < 0.01) and curiosity significantly
      influenced their decision regarding sexual initiation (chi2 = 8.689, p < 0.05).
      First-year students more often used condom at their first sexual intercourse
      (chi2 = 7.275, p < 0.01), and more rarely used withdrawal (chi2 = 6.380, p <
      0.05). At their last sexual intercourse, first-year students more often used any
      kind of protection (chi2 = 3.853, p < 0.05),more often used condom (chi2 =
      11.110, p < 0.01) and withdrawal (chi2 = 5.156, p < 0.05), and more rarely used
      contraceptive pills (chi2 = 4.405, p < 0.05). First-year students more often use
      condom in a permanent relationship (chi2 = 13.384, p < 0.05), and also plan to
      use it during following intercourse in the permanent relationship (chi2 = 17.575,
      p < 0.01). Growing condom use and decreasing risky sexual behaviour among
      students, as well as other adolescents and young adults needs to be maintained.
      Youth should learn before sexual initiation that only correct condom use at every
      sexual intercourse protects them against STI and human immunodeficiency virus
      (HIV). Sexual education and STI/HIV prevention programmes, positive role of media
      (television) and civil organisations that communicate with the youth can help
      that. Such changes among adolescents and young adults should have to be seen in
      student population as well.

PMID- 24851595
TI  - Attitudes towards and knowledge about homosexuality among medical students in
      Zagreb.
AB  - The aim of the study was to investigate whether students in their fifth and sixth
      years of medical school in Zagreb have homophobic attitudes and assess their
      knowledge about homosexuality. A survey was conducted among fifth and sixth year
      medical students during the 2009/2010 academic year. The survey consisted of
      general demographic data, two validated questionnaires--"Knowledge about
      Homosexuality Questionnaire" and "Heterosexual Attitudes towards Homosexuality
      Scale"--and questions about personal experiences created for this study. The mean
      knowledge scores were X = 14.8 out of 20. Furthermore, gender differences in
      attitudes were observed, indicating less negative attitudes among the female
      participants. The regression model was significant (ANOVA: Sum of Squares =
      38.065; df = 17, Mean Square= 2239, F = 10.6; p < 0.001) with 38% of explained
      variance. The significant predictor variables that indicate lower attitudes about
      homosexuality score were female gender (beta= -0.14, p = 0.015), sixth year of
      study (beta = -0.16, p = 0.009) and more knowledge about homosexuality (beta = 
      0.48, p < 0.001). Negative attitudes are present among the students; therefore,
      educational efforts should be included in the curricula of medical schools to
      diminish the negative perceptions of the lesbian, gay, bisexual and transgender
      community.

PMID- 24851596
TI  - The theoretical and practical knowledge of nurses and midwives regarding to the
      hepatitis-B virus (HBV) vaccination: a cross-sectional study in Konya--Turkey.
AB  - The aim of our cross-sectional study was to investigate the factors that affected
      Hepatitis-B Vaccination (HBV) knowledge of the nurses and midwives, serving at
      various medical facilities as part of the primary healthcare services in Konya,
      Turkey. The study was conducted during March 01-31, 2004, including 127
      consentient nurses and midwives (out of 161) serving at 22 different healthcare
      centers in the region. In the survey, their source of information with regards to
      HBV vaccination varied from continuing education programs (37%) to book or
      brochure reading (11.8%), and their formal nursing education (11%). A
      statistically significant relationship was found between the number of years
      employed in this profession and knowledge of Hepatitis markers that are done
      prior to the beginning of vaccination calendar (p = 0.01) (p < 0.05). Majority
      (74.8%) of the participants reported that they gave information to families about
      potential side effects of HBV vaccination. In conclusion we have suggested that a
      special training program should be given to nurses and midwives that included
      topics like Hepatitis markers, vaccine administration techniques, doses, proper
      record taking, briefing individuals and families.

PMID- 24851597
TI  - From Morisky to Hill-bone; self-reports scales for measuring adherence to
      medication.
AB  - There are a number of approaches to studying medication-taking behavior. Self
      report measures have the benefits of being cheap, easy to administer, non
      intrusive, and able to provide information on attitudes and beliefs about
      medication. Potential limitations to self-report are that the ability to
      understand the items, and willingness to disclose information, can affect
      response accuracy and, thus, questionnaire validity. A computerized systematic
      search of the PubMed databases identified articles on scales for medication
      adherence measuring using the MeSH terms medication adherence, compliance, and
      persistence combined with the terms questionnaire self-report. Adherence scales
      have identified mostly in the last few years (2005-2012). One of the main sources
      has been article (Lavsa et. al) which evaluated literature describing medication
      adherence surveys/scales to gauge patient behaviors at the point of care.
      Articles were included if they evaluated or reviewed self-reported adherence
      medication scale applicable to chronic diseases and with a good coefficient of
      internal consistency reliability (Cronbach's alpha (alpha)). Articles that
      contained data about self-report medication adherence scales use were included. A
      total of about one hundred articles were identified. Of those articles, 20% (20
      of 100) were included in the review because of their relevance to the article
      topic. This article describes various self-report scales by which to monitor
      medication adherence, their advantages and disadvantages, and discusses the
      effectiveness of their application at different chronic diseases. There are many
      self-report scales for measuring medication adherence and their derivatives (or
      subscales). Due to the different nature of the diseases, there is no gold
      standard scale for measuring medication adherence. It can be nevertheless
      concluded that the nearest to gold-standard is the Medication Adherence
      Questionnaire (MAQ) scale by Morisky et.al. but we found better internal
      consistency reliability in some other scales.

PMID- 24851598
TI  - Osteoporosis, spinal mobility and chest expansion index in patients with
      ankylosing spondylitis.
AB  - To determine the correlation between the bone mineral density (BMD) and spinal
      mobility and chest expansion index in patients with ankylosing spondylitis.
      Eighty patients with confirmed diagnosis of ankylosing spondylitis were included
      in this study. In all of them physical examination was performed including
      assessment of spinal mobility and chest expansion index. Bone mineral density of
      the lumbar spine (L1-L4, anteroposterior view) and at the left hip was measured
      by dual X-ray absorptiometry (DXA) in standard manner According to the WHO
      classification of osteoporosis, patients were classified in three groups (normal,
      osteopenic or osteoporotic) depending on the osteoporotic status in lumbar spine,
      hip and femoral neck region. Eighty patients (46 men and 34 women; age 25-73
      years) were included. Mean BMD for lumbar spine was 1.104 +/- 1.043 (T score:
      0.67 +/- 2.15) and for total hip was 1.057 +/- 0.899 (T score: -0.28 +/- 2.34).
      Significant difference in the mobility of thoracic spine was observed in patients
      in regard to the WHO classification of osteoporosis in lumbar and femoral region
      (p = 0.031, Oneway Anova for osteoporosis of lumbar region; p = 0.022, Oneway
      Anova for osteoporosis of total hip region). Mean value for the chest expansion
      index was 3.07 +/- 1.66 cm. Chest expansion index was significantly reduced in
      patients having osteoporosis in lumbar and total hip region (p = 0.015, Oneway
      Anova for osteoporosis of lumbar region; p = 0.038, Oneway Anova for osteoporosis
      of total hip region). The observation that reduced mobility of thoracic and
      lumbar spine and chest expansion index occured in patients with low BMD in lumbar
      and total hip region suggest that osteoporosis should be monitored more
      frequently in patients with AS.

PMID- 24851599
TI  - Quality of life in Croatian metastatic melanoma patients.
AB  - The aim of this study was to examine the quality of life (QoL) in 40 Croatian
      metastatic melanoma patients who had completed at least first-line treatment and
      to see if there was a correlation between QoL parameters and serum lactate
      dehydrogenase (LDH). LDH levels were measured and all patients clinically
      examined between April and September 2013. Two QoL questionnaires were used for
      patient self-evaluation: the European Organization for Research and Treatment of
      Cancer Quality of life Questionnaire (EORTC QLQ-C30) and the Dartmouth Primary
      Care Cooperative Research Network and the World Organization of National
      Colleges, Academies, and Academic Associations of General Practitioners/Family
      Physicians (COOP/WONCA) charts. The average EORTC QLQ-C30 score for global health
      status (GHS) was 41.204. The average scores for functional scales were high, with
      the exception of emotional functioning (65.02). Blood LDH levels positively
      correlated with the Eastern Cooperative Oncology Group (ECOG) status (r = 0.415;
      p < 0.01) and pain (r = 0.345; p < 0.05), but not with any functional or
      COOP/WONCA scores. Global health status (GHS) positively correlated with patient
      age at the time of evaluation (r = 0.386; p < 0.05) and age at the time when
      metastatic disease had been diagnosed (r = 0.366; p < 0.05). Quality of life for
      the studied group of metastatic melanoma patients in Croatia can be considered
      generally good, with the exception of emotional functioning and symptoms of
      fatigue, dispnoea, insomnia, and financial difficulties.

PMID- 24851600
TI  - The burden of hospitalised carcinoma patients in Osijek-Baranja County, Croatia,
      1998-2010.
AB  - The purpose of this paper was to determine the number and trend of
      hospitalisations caused by carcinoma in the Osijek-Baranja County, to to
      determine the proportion of these hospitalizations compared to all other
      hospitalization, as well as to determine the burden put on the hospitals by
      external patients (those not residing in the Osijek-Baranja County area). There
      has been an average of 10.1% of hospitalisations caused by carcinoma in the
      Osijek-Baranja County from 1998 to 2010. In the aforementioned period there have
      been an average 15.9% days of hospitalisation caused by carcinoma. Patients
      hospitalised due to carcinoma stay in hospital 5.3 days longer than other
      patients. The number of hospitalisations as a whole, as well as those due to
      carcinoma, is rising, while the number of days of hospitalisation per patient is
      decreasing. The number of hospitalisations which refer to men is slightly higher
      than for women (51.2%:48.8%). Almost one third of patients hospitalised are not
      residents of the Osijek-Baranja County due to a gravitational hospitalisation
      instance. Residents of northern Bosnia and Herzegovina are the most common
      patients being treated in our county. This burden has to be taken in to account
      when planning our health care due to the geographically, economically and
      politically specific situation of Osijek-Baranya County. This data has to be
      taken in to account when further planning our health care, as to relieve the
      acute medical situation hospitals of some of their burden, as well as to provide
      adequate care to patients suffering chronically from carcinoma. It is especially
      important to stress out that our county does not have a palliative care facility,
      nor a hospice for the terminally ill.

PMID- 24851601
TI  - Malignant neoplasms of digestive organs (C15-C26) in the Osijek-Baranja County,
      Croatia.
AB  - The Institute of Public Health for the Osjek-Baranja County (OBC) has processed
      the data on cancer patients that were collected from mandatory county hospitals
      data reports, county bureaus of statistics and the County Register of Deaths. The
      cancers were defined according to the International Statistical Classification of
      Diseases and Related Health Problems, 10th Revision (ICD-10), codes of malignant
      neoplasms of digestive organs (C15-C26). The aim of this article is to show the
      size of the problem and the burden of the health care system caused by cancers of
      the digestive system (C15-C26) in the OBC in the period 2001-2006. This article
      deals with cancer incidence and mortality data, appertaining age distribution,
      cancer survival, median age at diagnosis and at death and length of stay in
      hospitals. The overall incidence and mortality rate from cancer group C15-C26
      (101.1 and 80/100,000, respectively, EU standard population) declined in all age
      groups, comparing the data originating from the 2001-2003 period to the data
      referring to the 2004-2006 period. The median age at diagnosis of cancer was 67.8
      years with a shift of 0.91 year up in second period (the median age in the first
      period was 67.3 years and in the second one 68.2 years). The median age at
      diagnosis of cancer in females was 69.7 years while in males was 66.3 years,
      which represents a difference of 2.9 years in favour of females. The overall
      relative survival rate of all ages was 23.6%. This figure was slightly bigger for
      females (24.3%) than for males (23.1%). Concerning all age groups, the number of
      hospital admissions of males increased during the observation period while the
      number of hospital admissions of women decreased at the same time. The average
      length of stay over the six years did not changed significantly. Group of cancer
      C15-C26 was the most common group of cancers regarding both genders. The five
      year relative survival as one of the reliable benchmarks of the quality of the
      health care system needs to be raised to a great extent in order to come nearer
      to the EU average within a short period of time.

PMID- 24851602
TI  - Assessment of nutritional status in cancer patients in Osijek health area center.
AB  - The aim of this research was to perform the nutritional screening and clinical
      assessment of malnutrition and of cachexia as well as the need for enteral
      nutritional support. We used an international questionnaire for nutrition
      screening and clinical assessment of malnutrition. 103 cancer patients
      participated in the research. The results indicate that 80patients (78%) have
      recently unintentionally lost weight in the last six months. Of those 80 patients
      12 (15%) have lost more than 15 kilograms. Three patients (3%) suffer from hunger
      because of their inability to eat. Presence of multiple (3 or more) symptoms
      (nausea, vomiting, diarrhea or anorexia) was reported by 11 patients (11%).
      Severe work dysfunction was found in 28 patients (27%). 14 patients (14%)
      experience significant loss of musculature (musculus quadriceps femoris, musculus
      deltoideus). The obtained results indicate that 15patients (14%) are severely,
      and 39 patients (38%) are moderately undernourished. This survey confirmed the
      significance of nutritional screening in cancer patients, as it detected 30
      patients (29%) who required introduction of enteral nutrition.

PMID- 24851603
TI  - Emergency surgery for large bowel obstruction caused by cancer.
AB  - There are several options for surgical treatment of large bowel obstruction
      caused by cancer, depending on location of obstruction, intraoperative local
      findings (perforation, peritonitis, bowel dilatation proximal to obstruction) and
      patients' condition. Resection and anastomosis as one stage surgery would be
      prefered procedure. Anastomotic leakage, on the other hand, highly elevates risk
      of mortality and mobidity. The most important question is whether to, in
      resectable cases, perform primary resection with anastomosis or not. This study
      was retrospective and included 40 patients that have undergone emergency surgery
      for large bowel obstruction caused by cancer. According to whether resection and
      anastomosis was made at initial surgery or not, patients were grouped in group A
      (N = 18) and group B (N = 21), respectively. We have analysed the type of
      surgical procedure, days of hospitalization, mortality, anastomotic leakeage,
      wound infection and other postoperative complications. Our results show that
      there is no major difference in mortality and morbidity in these two groups,
      suggesting that for selected patients primary resection and anastomosis is a safe
      option of tratment with acceptable risk. Since there are no strict guidelines or
      scorring system which would point the tratment option the decision about the
      choice of procedure still remains the burden of surgeon and depends on its
      experience and subspeciality. Our experience recomends primary resection and
      anastomosis except in cases of bowel perforation on tumor site, in cases of
      extreme dilatation and atony of bowel proximal to obstruction site and severe
      hypoproteinemia and anemia.

PMID- 24851604
TI  - Incidence and prevalence of inflammatory bowel disease in Vukovarsko-Srijemska
      County, Croatia, 1991-2000 and 2001-2010: a population-based study.
AB  - Inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis
      (UC), were retrospectively assessed on the incidence and prevalence in Vukovarsko
      Srijemska County, continental Croatia. There were a total number of 150 patients,
      119 with UC and 31 with CD. Of them, 79.3% were patients with UC, indicating a
      predominant participation of UC in the sample. Comparisons between the period of
      surveillance, 2001-2010, and the decade before, 1991-2000, showed a significant
      increase in the incidence rates of both, UC and CD (UC 3.5, CD 0.95, 2001-2010,
      and UC 1.0, CD 0.45, 1991-2000). Comparison of this study with that performed in
      Primorsko-Goranska County, coastal Croatia, revealed different distribution
      patterns of IBD. In Primorsko-Goranska County, significantly higher incidence and
      prevalence rates of UC and CD and rather equal ratios between two diseases, were
      observed. The results are indicative of the differences between more developed
      Western and less developed Eastern parts of Croatia.

PMID- 24851605
TI  - Severe acute pancreatitis as a part of multiple dysfunction syndrome.
AB  - Acute pancreatitis is a disease with various degrees of clinical manifestations.
      Mild and moderate severe acute pancreatitis is an illness characterized with
      chemical inflammation which, in general, passes without major complications.
      Clinical picture of severe acute pancreatitis other side is commonly complicated
      with functional deterioration of other organs, and frequently has characteristics
      of multiple organ dysfunction or failure syndrome with or without bacterial super
      infection. We studied 82 patients admitted to the intensive care unit with severe
      acute pancreatitis, 14 died. The mortality was in statistically significant
      correlation with the severity of clinical condition at admission assessed by
      APACHE II score, and higher Ranson's and Glasgow criteria by admission. Adequate
      volume supplementation, on time, as well as percutaneous drainage of infected
      pancreas collection reduces a risk of pure outcome.

PMID- 24851606
TI  - A correlation between the expression of estrogen receptors and progesterone
      receptors in cancer cells and in the myometrium and prognostic factors in
      endometrial cancer.
AB  - Endometrial cancer is the most common gynecological malignancy in Croatia. The
      aim of this study was to determine the immunohistochemical expression of estrogen
      receptors (ER) and progesterone receptors (PGR) in cancer cells and in the
      myometrium and to correlate it with prognostic factors of endometrial carcinoma.
      ER positivity in carcinoma cell nuclei was found in 42 cases (73.7%) and PGR
      positivity was found in 39 cases (68.4%). Loss of ER in carcinoma cell nuclei
      correlated with larger tumor size (p = 0.041), poor carcinoma differentiation (p
      = 0.012), a more aggressive histological type (p < 0.001), lymphovascular space
      invasion (p = 0.002) and a higher surgical stage (p = 0.037). Loss of PGR in
      carcinoma cell nuclei correlated with an increased age in patients (p = 0.009),
      poor tumor differentiation (p = 0.002), a more aggressive histological type (p <
      0.001), lymphovascular space invasion (p = 0.002) and a higher surgical stage (p
      < 0.001). The lower expression of both receptors did not correlate with the depth
      of myometrial invasion. Regarding the status of receptors in the myometrium, loss
      of PGR in the myometrium correlated with a more aggressive histological type (p =
      0.005) and a lack of ER in the myometrium tended to correlate with tumor growth
      (p = 0.059). In conclusion, the loss of both hormone receptors in carcinoma cells
      and loss of PGR in the myometrium was a predictor of a more aggressive type of
      endometrial cancer and a poor prognosis.

PMID- 24851607
TI  - The level of serum pro-matrix metalloproteinase-2 as a prognostic factor in
      patients with invasive ductal breast cancer.
AB  - This paper analyses data of 150 female patients undergoing surgical treatment for
      invasive ductal breast cancer at the University Hospital for Tumors from January
      2006 to January 2007. The control group consisted of 50 healthy women. The
      patients were classified into three groups, depending on their tumor
      differentiation, i.e. grade I, II and III tumor groups. Each group consisted of
      50 patients. Traditional prognostic factors including: age, tumor size and
      differentiation grade, axillary lymph node status, presence of distant
      metastases, steroid receptor findings, vascular invasion of the primary tumor,
      presence of an extensive intraductal component (EIC) in the primary tumor, HER-2
      protein expression were evaluated. Both the patients' and controls' serum levels
      of proMMP-2 (pro-matrix metalloproteinase-2) were assessed using the ELISA
      method. The aim of the study was to assess pathohistological prognostic factors
      and the level of serum proMMP-2 in the three patient groups and the controls,
      compare the relationship between the prognostic factors and the level of serum
      proMMP-2 in the patient groups, and upon the results, determine possible features
      of proMMP-2 as a prognostic factor in breast cancer patients. The study results
      showed no difference in proMMP-2 concentrations between the three patient groups
      and the controls. No statistically significant difference in the serum proMMP-2
      concentration was found between the patient groups, although the grade III group
      values were the highest showing a trend toward statistical significance.
      Comparison of proMMP-2 and prognostic factors revealed a statistically
      significant correlation between proMMP-2 and age in patients with histologic
      grade I tumors. There was no statistically significant correlation between
      circulating proMMP-2 and other pathohistological prognostic factors.

PMID- 24851608
TI  - Association study of cytochrome P450 1A1*2A polymorphism with prostate cancer
      risk and aggressiveness in Croatians.
AB  - Cytochrome P450 1A1 (CYP1A1) is an enzyme participating in the bioactivation of
      various endogenous and environmental reactive compounds that can bind to DNA and
      thus induce cancerogenesis. Gene encoding the enzyme is expressed in the prostate
      tissue and is polymorphic. CYP1A1*2A gene polymorphism is associated with
      elevated enzyme activity and/or inducibility which can lead to accumulation of
      genotoxic compounds and consequently to cancerogenesis. We examined the
      association of this polymorphism with prostate cancer (PCa) risk and
      aggressiveness. The case-control study consisted of 120 PCa patients and 120
      benign prostatic hyperplasia (BPH) controls, in Croatian population. Regarding
      aggressiveness, PCa patients were grouped according to the Gleason score (GS),
      tumor stage (T) and existence of distant metastasis (M). The polymorphism was
      analyzed using real-time polymerase chain reaction (PCR). We did not observe
      association of mutated allele with PCa risk, neither with PCa aggressiveness.
      Furthermore, frequency of polymorphic genotype was slightly higher in BPH group
      (16.6% vs. 14.2%, respectively) and also in less aggressive form of PCa (20.4%
      vs. 9.6% for GS < 7; 15.6% vs. 9.1% for T < 3; 16.7% vs. 10.0% for no distant
      metastasis). Comparing our findings with other published results, we can assume
      that the ethnicity influence the genotype distribution and thus may affect the
      etiology of PCa, even possibly in the way to cause an opposite effect among
      different ethnic groups. Given the small number of participants, results should
      be validated on the larger sample size.

PMID- 24851609
TI  - Comparison between clinical significance of serum proinflammatory protein
      interleukin-6 and classic tumor markers total PSA, free PSA and free/total PSA
      prior to prostate biopsy.
AB  - The aim of the study was to clarify whether serum levels of proinflammatory
      cytokine interleukin-6 (IL-6) could be a useful marker in prostate diseases.
      Serum IL-6 was determined prior to prostate biopsy procedure in 82 patients with
      prostate adenocarcinoma (PCa), 25 patients with benign prostatic hyperplasia
      (BPH), 24 patients with high-grade prostatic intraepithelial neoplasia (PIN) and
      17 patients with chronic prostatitis. Serum IL-6 levels were compared with total
      PSA (tPSA), free PSA (fPSA) and the free/total ratio (f/tPSA) serum levels.
      Statistically significant difference was not found in serum IL-6 levels among the
      four groups (p = 0.088). However, the patients with poorly differentiated PCa
      with Gleason score (GS) 4 + 3 = 7 and > 7 had significantly higher serum IL-6
      levels than the patients with moderately differentiated PCa with GS 3 + 4 = 7 and
      < 7 (p = 0.007). The findings suggest that serum IL-6 level might be a
      potentially useful marker for poorly differentiated PCa.

PMID- 24851610
TI  - Ultrasound distinction between simple recurrent urinary tract infections and a
      specific bladder wall inflammatory entity called cystitis cystica.
AB  - A specific representative of recurrent urinary tract infections (UTI) called
      cystitis cystica (CC) was assessed by ultrasound. The aim of the study was to
      delineate, by means of ultrasound measurement (US) of bladder wall thickness
      (BWT), the children with mere repeated UTI from those prone to frequent UTI due
      to CC. Two groups were compared, the control group of 30 with recurrent UTI
      without US CC BWT changes, and the group of 30 children with characteristic CC
      bladder wall thickening in whom cystoscopy was performed for verification the
      diagnosis of CC. BWT of > 3 mm (> 2.8 mm and > 3.3 mm) was found as cut-of value
      for distinction of CC versus simple recurrent UTI. US BWT measurement is useful
      in diagnosing CC and therefore valuable in decision about need of UTI
      prophylaxis.

PMID- 24851611
TI  - The risk of developing endemic nephropathy in subjects with proteinuria.
AB  - Endemic nephropathy is a chronic tubulointerstitial disease characterized by
      early damage to the proximal tubule, with low-molecular weight proteinuria being
      an important hallmark and possible tool for early diagnosis. The aim of this
      retrospective cohort study was to assess the risk of developing endemic
      nephropathy in subjects with proteinuria from the endemic region in Croatia. The
      cohort study included subjects with proteinuria determined by the sulfosalicylic
      acid method (after 1988 with strip method), involved in the field survey
      conducted in the Croatian endemic village of Kaniza in 1975 and followed up until
      1997. Subjects with endemic nephropathy established at the first visit and
      patients that failed to present for follow up visits after 1975. were excluded.
      In the field survey group that consisted of 624 subjects (286 male and 338
      female), proteinuria was established in 157 subjects. Upon the application of
      exclusion and inclusion criteria, the study cohort included 111 of 157 subjects.
      The mean follow up was 7.26 years (95% confidence interval 4.06-10.46 years).
      During the follow up period, 19 (17%) subjects with initial proteinuria developed
      endemic nephropathy. The incidence density of endemic nephropathy among subjects
      with proteinuria was 1.3 per 100 persons/year. Estimated risk was 0.0137
      (confidence interval 0.0087-0.0214) per year of exposure. The presence of
      proteinuria determined by the sulfosalicylic acid or test strip in subjects from
      the endemic village indicated that endemic nephropathy would develop in 1.3 of
      100 subjects with proteinuria per year.

PMID- 24851612
TI  - Importance of determination of urine neutrophile gelatinase associated lipocalin
      in early detection of acute kidney injury.
AB  - Acute kidney injury (AKI) is a complex, frequent and serious clinical problem
      with high rate of mortality. Therefore there is a serious need for early
      detection of AKI, with a tendency to detect early stage--RISK dut to start with
      therapy as soon as possible and prevent irreversible changes in renal function.
      Study's purposes were to explore the rhythm of urine neutrophile gelatinase
      associated lipocalin (urine NGAL) concentration changes before and after
      cardiovascular surgery and compare results of urine NGAL values with results of
      serum creatinine and creatinine clearance as main diagnostic indicators of renal
      function in order to define role of urine NGAL biomarker in early diagnosis of
      acute kidney injure. In the prospective clinical study 150 cardiovascular surgery
      patients were included. Basal value and concentration of urine NGAL were tested
      3, 6 and 12 hours after cardiovascular surgery, and concentration of serum
      creatinine was tested once per day first three days after surgery. Also
      creatinine clearance value was calculated according to Cockrof-Goult formula.
      After above mentioned, rate of acute kidney injure was estimated according to
      RIFLE criteria. The study results showed that the value of urine NGAL was
      elevated above cutt-off after cardiac operation in a group of patients who
      developed AKI (defined according to RIFLE criteria). There were statisticaly
      significant difference between all four measerments (p < 0.05). There were also
      moderate positive correlation (0.500 and 0.502) between urine NGAL values and
      percentage difference of serum creatinine and creatinine clearence. All that
      indicate that higer values of urine NGAL are followed by higher percentage
      difference of serume creatinine and creatinine clearence. By using of automated
      urine NGAL test detection of acute kidney injure is posible 24-48 hours earlier
      comparing with actual results acquired by determination of serum creatinine
      concentration. The results of this study will indicate urine NGAL as a reliable
      biomarker of early acute kidney injure. A combination of early and late markers
      of kidney damage (urine NGAL, serum creatinine) can greatly contribute to better
      control the outcome of all those who are a risk group for the development of AKI.

PMID- 24851613
TI  - Effect of chorioamnionitis on mortality, early onset neonatal sepsis and
      bronchopulmonary dysplasia in preterm neonates with birth weight of < 1,500
      grams.
AB  - The aim of the study was to investigate the effects of chorioamnionitis on
      mortality and early onset neonatal sepsis (EONS) and bronchopulmonary dysplasia
      (BPD) in preterm neonates with birth weight < or = 1,500 g. The study included
      395 preterm infants born at the Zagreb Clinical Hospital Center, from January
      2001 to December 2005. All the placentas from preterm deliveries were sent for
      pathological examination. The patients were categorized into two groups: one
      including patients with chorioamnionitis at placental histology (47%) and the
      other control group without chorioamnionitis (53%). Neonates were distributed
      into 3 groups according to gestational age: the first group with 132 (33%)
      infants born at < or = 28 weeks of gestation, the second with 202 (52%) infant
      born from 29 to 32 weeks of gestation and the third with 61 (15%) infants born at
      > or = 33 weeks gestation. Chorioamnionitis was diagnosed significantly more
      often in the first gestational age group (91/132-69% of infants, chi2 = 51.307, p
      < 0.05). The outcome was lethal in 67/395 (17%) patients; 55% of them had
      chorioamnionitis (chi2 = 2.421, p > 0.05). Lethal outcome ensued in 54/132 (41%)
      infants from the first gestational age group; 30/54 (55%) were born from
      pregnancies complicated by chorioamnionitis. In comparison with the control
      group, mortality was significantly higher in the group of premature infants with
      gestation < or = 28 weeks whose placentas showed chorioamnionitis (chi2 = 7.645,
      p < 0.01). EONS was probable or confirmed in 100/395 (25%) infants; in 66/100
      (66%) infants pregnancy was complicated by chorioamnionitis (chi2 = 22.396, p <
      0.01). BPD developed in 25/395 (6%) infants; in 12/25 (48%) infants placentas
      showed chorioamnionitis (chi2 = 0.022, p > 0.05). In conclusion, premature
      neonates from pregnancies complicated by chorioamnionitis are more often born at
      < or = 28 weeks of gestation. Chorioamnionitis in neonates whose gestation is <
      or = 28 weeks leads to a significantly higher rate of mortality than in neonates
      with a longer gestation period. A greater incidence of EONS was proven in the
      group of infants with chorioamnionitis. The difference between the incidence of
      BPD in preterm infants born from pregnancies complicated by chorioamnionitis and
      the control group was not significant.

PMID- 24851614
TI  - Unconjugated pathological jaundice in newborns.
AB  - Neonatal jaundice is the occurrence of elevated bilirubin levels in the blood. It
      may be physiological or pathological. If the concentration of non-conjugated
      bilirubin in the blood is too high, it breaches the blood brain barrier and
      bilirubin encephalopathy occurs with serious consequences for the child. The aim
      of the research was to examine the incidence frequency of unconjugated pathologic
      jaundice in newborns and connect it to some epidemiological variations (medical,
      social, demographic) as well as to prove the increased frequency of jaundice in
      children born by stimulation and labour induction. The study included 800
      infants: 198 (24.8%) of them did, and 602 (75.2%) did not suffer from jaundice.
      Statistical analysis confirmed the association between the onset of jaundice in
      newborns and the following parameters: gestational age, birth weight, maternal
      infections and other illnesses during pregnancy and premature rupture of
      membranes as complications during labor and the mode of delivery.

PMID- 24851615
TI  - Changes in dietary intake and body weight in lactating and non-lactating women:
      prospective study in northern coastal Croatia.
AB  - Postpartum weight retention is a risk factor for the development of midlife
      obesity. Since dietary intake and breastfeeding practice could be promoters of
      weight loss during postpartum, the objective of this study was to investigate
      their influence on weight retention during six months postpartum. The study
      sample consisted of 83 lactating and 76 non-lactating Croatian women who were
      examined at three measurement waves: at 1 month +/- 1 week, 3 months +/- 1 week
      and 6 months +/- 1 week postpartum. At each measurement wave, two consecutive 24
      hour dietary recalls were collected, and body weight measurements were made. Both
      groups had a daily energy intake lower by about 25% than recommended. Although
      both groups continuously decreased energy and macronutrient intake, lactating
      women had energy intake higher by 205 kcal (p = 0.048) and 370 kcal (p < 0.001)
      after one and three months, respectively. At six months postpartum lactating
      women had a higher intake of fat (p = 0.036) but a lower intake of protein (p =
      0.009) compared with non-lactating mothers. After six months, lactating women
      retained 101.9% of pre-pregnancy weight, which was significantly less than the
      percentage of weight retained among non-lactating women (p = 0.014). Multiple
      regression analysis showed that weight retention were predicted by: type of
      feeding (beta = -0.281; p <0.001), and time since parturition (beta = -0.151; p <
      0.001), while gestational weight gain (P = 0.491; p < 0.001), energy intake (b =
      0.157; p < 0.001) and energy derived from fat (beta = 0.122; p = 0.035) were
      positive predictors. We concluded that the dietary intake of Croatian women and
      breastfeeding practice over six months significantly influence their weight loss.

PMID- 24851616
TI  - The effects of parental smoking on anthropometric parameters, peak expiratory
      flow rate and physical condition in school children.
AB  - Passive smoking in children is a considerable health problem, mainly arising from
      parental smoking. The objectives of the present cross-sectional study were to
      assess the impact of passive smoking on 1) anthropometric parameters; 2) peak
      expiratory flow rate (PEFR); and 3) physical condition in school children. The
      target population included 177 children attending elementary school 5th to 8th
      grade. Study subjects were divided into two groups according to parental smoking
      habits. Body weight and height were determined using a digital weighing scale and
      digital stadiometer; PEFR was measured between 8 a.m. and 10 a.m. using a Peak
      Flow Meter; and physical condition was assessed by the 6-minute run test. Sixty
      six percent of study children were exposed to passive smoking. The children of
      smoking parents had higher BMI [18.79 (17.50-21.13) kg/m2] than children of
      nonsmoking parents [17.90 (16.00-20.00) kg/m2; p = 0.036]. There was no
      statistically significant difference in body height and weight. The children of
      smoking parents had statistically lower values of PEFR [M(IQR) = 84 (78-88)%,
      M(IQR) = 94 (89-101)%, respectively; p < 0.0001] and 6-minute run test than
      children of nonsmoking parents [M(IQR) = 2(1-3), M(IQR) = 4(3-5); respectively; p
      < 0.0001]. The results of the present study showed that exposure of school
      children to passive smoking by their parents resulted in an increase of BMI,
      impairment of lung function, and impairment of physical condition, especially in
      children of both smoking parents.

PMID- 24851617
TI  - Variation in indicators of respiratory functions among Warsaw adolescents in
      relation to ambient air pollution and smoking.
AB  - This work presents results of studies on secondary school adolescents inhabiting
      two regions of Warsaw: Srodmiescie district (Downtown) and Miedzylesie (Wawer
      district - Vicinity), conducted in 2006. These two districts significantly differ
      according to air pollution, which is much higher in Downtown than in Vicinity.
      The sample consists of 219 boys and 225 girls aged 13-16 years. The measurements
      included body height and weight and 8 respiratory variables of lung function: VC,
      FEV1, TV, MV, IRV, ERV, Ap, RR. Additionally information about education of
      parents, number of children in family, number of rooms in a house/apartment,
      smoking habits of pupils and their parents were provided. Sib-sib size, parents
      education level and number of rooms in apartment or house were included in a
      principal component analysis (PCA) to obtain a common factor representing general
      socio-economic status (SES) for families. First factor scores were used as
      covariates in the further analysis. The influence of air pollution on respiratory
      variables was evaluated using the analysis of covariance (ANCOVA). The results
      show that there are significant relations of air pollution to Ap, MV and IRV and
      smoking habits of individuals on their MV and TV. In the heavier polluted region
      there are observed longer time of Ap and higher values of IRV There is an
      opposite reaction of MV on air pollution and smoking. The MV values are lower in
      the heavier polluted area but presents greater values in smoking individuals.
      Also values of TV are greater if individuals smoke comparing with non smokers.

PMID- 24851618
TI  - Risk management in air protection in the Republic of Croatia.
AB  - In the Republic of Croatia, according to the Air Protection Act, air pollution
      assessment is obligatory on the whole State territory. For individual regions and
      populated areas in the State a network has been established for permanent air
      quality monitoring. The State network consists of stations for measuring
      background pollution, regional and cross-border remote transfer and measurements
      as part of international government liabilities, then stations for measuring air
      quality in areas of cultural and natural heritage, and stations for measuring air
      pollution in towns and industrial zones. The exceeding of alert and information
      threshold levels of air pollutants are related to emissions from industrial
      plants, and accidents. Each excess represents a threat to human health in case of
      short-time exposure. Monitoring of alert and information threshold levels is
      carried out at stations from the state and local networks for permanent air
      quality monitoring according to the Air Quality Measurement Program in the State
      network for permanent monitoring of air quality and air quality measurement
      programs in local networks for permanent air quality monitoring. The State
      network for permanent air quality monitoring has a developed automatic system for
      reporting on alert and information threshold levels, whereas many local networks
      under the competence of regional and local self-governments still lack any fully
      installed systems of this type. In case of accidents, prompt action at all
      responsibility levels is necessary in order to prevent crisis and this requires
      developed and coordinated competent units of State Administration as well as self
      government units. It is also necessary to be continuously active in improving the
      implementation of legislative regulations in the field of crises related to
      critical and alert levels of air pollutants, especially at local levels.

PMID- 24851619
TI  - The examination of the heart rate recovery after anaerobic running in soccer
      players.
AB  - The purpose of this study was to examine the heart rate recovery depending on
      anaerobic running. A total of 23 professional soccer players who were player of
      Turkish Super Leagues, were examined. Anaerobic Run test was applied to the
      soccer players and their heart rates were recorded before running, just after
      running, in 3rd and 6th minutes of recovery period. Any statistical differences
      were not found between the heart rates before run and in 6th minute after run (p
      > 0.05). On the other hand, there was a statistical difference between the heart
      rates before run, after run and in 3rd minute after run; the heart rates after
      run and before run; the heart rates in 3rd and 6th minutes of recovery (p <
      0.05). A relationship was determined between the heart rates after run, before
      run (r = 0.457) and in 3rd minute of recovery (r = 0.537) and the heart rates in
      3rd and 6th minutes of recovery (r = 0.629). On the other hand, no relation was
      found between the heart rates before run, in 3rd minute recovery (r = 0.247) and
      in 6th minute of recovery (r = -0.004) and the heart rates just after run and in
      6th minute of recovery (r = 0.280) (p > 0.05). In conclusion, even if the
      increase of heart rate occurring after anaerobic run doesn't completely return to
      normal in 3rd minute of recovery, it will supply the athlete with a suitable
      condition for the second loading with regard to efficient rest. It is thought
      that a rest over 3 minutes should be given for athletes to make the heart rate
      after anaerobic run return to normal.

PMID- 24851620
TI  - Diagnostic value of MPO in patients admitted for suspected acute coronary
      syndrome--a study of adult in Mostar, Bosnia and Herzegovina.
AB  - We assessed the diagnostic efficacy of plasma Myeloperoxidasis (MPO) alone or in
      combination with cardiac troponin I (cTnI) for detecting ACS in patients
      presenting with chest pain initiating within 24 h before the hospital admission.
      In this prospective cohort study were included all respondents who have visited
      outpatient clinic of internal diseases, University Hospital Mostar because of
      chest pain and suspected acute coronary syndrome within 24 h of the onset of the
      period of 6 months and the total sample consisted of 114 patients. Troponin and
      myeloperoxidase were significantly positively correlated at the beginning of
      treatment, myeloperoxidase was significantly positively associated with adverse
      cardiovascular events during hospitalization and myocardial infarction (p <
      0.05), with the regression analysis did not show a significant predictor in the
      development of myocardial infarction (p > 0.05). Sensitivity of myeloperoxidase
      as a valid test detection of myocardial infarction at baseline was 0.15 and
      specificity was 0.85, suggesting good diagnostic value usable in the clinical
      practice.

PMID- 24851621
TI  - Body mass index and anthropometric characteristics of the hand as risk factors
      for carpal tunnel syndrome.
AB  - Carpal tunnel syndrome (CTS) is the most common peripheral entrapment compressive
      neuropathy in the upper limbs. It is often correlated with personal factors of
      individuals, not only with certain medical conditions and jobs. The study aimed
      at clarifying the association of carpal tunnel syndrome with anthropometric
      characteristics of the hand and body mass index (BMI) as independent risk
      factors. A total of 100 subjects participated: 50 patients with electro
      diagnostically confirmed CTS and 50 healthy volunteers without CTS symptoms as
      control group, each group including 37 women and 13 men. Height, weight, BMI,
      wrist depth and width, wrist index, hand shape index, digit index, palm length,
      palm width, third finger length and ratio of hand length to body height were
      assessed in all participants. To determine independent risk factors for CTS,
      multiple logistic regression was used. Wrist index and wrist width were
      significantly higher in CTS patients than in the control group. The estimated
      optimal threshold of wrist index for prediction of CTS was 0.69, above which the
      odds for CTS were estimated to increase 42-fold. Elevated BMI correlated with
      bilateral CTS in both genders. The study identified wrist index, BMI and ratio of
      hand length to body height ratio as independent risk factors for CTS.

PMID- 24851622
TI  - Anthropometric indices of obesity and potential health risk in adult rural
      population from Backa and Banat--the Republic of Serbia.
AB  - Obesity, along with other unhealthy living habits, nowadays represents one of the
      greatest risk factors for various diseases. Vojvodina is a part of Serbia where a
      high percentage of the overweight has been recorded since the period of former
      Yugoslavia. The aim of this study therefore was to determine the percentage of
      adults with potential health risk using the indices of obesity. The
      anthropological study was conducted from 2001 to 2006. The tested group consisted
      of 4504 individuals, 1965 men and 2539 women. The mean age of the sample was
      40.61 +/- 11.29. The data were collected in 46 villages in Backa and Banat, in
      the central and north-east parts of Vojvodina, situated in the north of Serbia.
      The investigation included the height, weight, waist and hip circumference.
      Nutritional condition was determined using the body mass index (BMI kg/m2), while
      the waist circumference and WHR were used for assessing the central obesity.
      According to the average BMI (26.86 kg/m2 males, 25.80 kg/m2 females), the
      population of Backa and Banat is characterised with pre-obesity. In total, 58.47%
      individuals of both sexes are with excessive body weight, 38.52% of them being
      classified as overweight and 19.48% as obese. Central obesity is more frequent in
      males aged up to 40, while in females it is more present above the age of 50. A
      higher waist circumference (males > 94 cm; females > 80 cm) is observed in 58% of
      males and 55% of females, with the risk value (males > 102 cm; females > 88 cm)
      recorded in 32% of men and women. The indices of obesity indicate a potential
      health risk for more than a half of the subjects in this study. The data
      therefore point to the necessity of introducing educational programs for
      promoting good nutrition and healthy living habits that would ultimately reduce
      the number of individuals with health risk.

PMID- 24851623
TI  - Prevalence of depressive symptoms among college students and the influence of
      sport activity.
AB  - The present study asses the prevalence of depressive symptoms among college
      students in Split, Croatia, and positive influence of sport activity on
      decreasing the depression symptoms. Authors screened all 664 college students of
      the first year of study. All of them were over the 18 years and the mean age was
      19.4 +/- 1.2 years. There were 466 females (70.2%) and 178 (26.8%) males. They
      answered The Beck Depression Inventory (BDI) and questionnaire about their sport
      activity (no sport activity, recreational and active in sports). For the purpose
      of the analysis depressive symptoms were defined as a score of > 11. Chi-square
      and Mann-Whitney test were used for data analysis. 9.4% of the students had
      significant depression symptoms (score > 11). No one student had score > 26
      (symptoms of major depression). Statistically significant lower score on BDI have
      students who are active in sports (score median = 3) compared to group of
      recreational (score median = 4) and in correlation to group who are not active in
      sports (score median = 5) (Kruskal-Wallis: p < 0.001). In the group of active in
      sports (N = 254) there are only 5.5% with depressions symptoms, while in the
      group of non active in sports (N = 60) are 18 depressive (chi2-test: p = 0,005).
      Females are statistically more depressed than males (chi2-test: p = 0.01). In the
      female group 49 (10.5%) are depressed, and in the male group are 9 (5%). Compared
      to gender in separate analysis we did not find correlation of decreasing
      depression symptoms and sport activity among males (chi2-test: p = 0.47), while
      in females we find that sport activity has significant effect (chi2-test: p =
      0.026). Our results shoved moderate values of depression symptoms among college
      population in Split, Croatia. More females than males experienced depressive
      symptoms. While sport activity did not have significant influence on the
      depression in male population, it has significant influence in reducing the
      depression symptoms among females.

PMID- 24851624
TI  - The relationship of morphology and motor abilities to specific table tennis tasks
      in youngsters.
AB  - The aim of this research was to establish the relationship of certain basic motor
      abilities and morphological characteristics and efficacy in specific table tennis
      tasks. The research sample consisted of cadet category table tennis players (N =
      101; aged 10.52 +/- 0.78 years, training experience 2.8 +/- 0.93 years). The
      participants were measured as they performed 24 motor tasks, along with 15
      anthropometric measures and 3 specific table tennis tests. Indicators of the
      relationship between morphological characteristics and motor abilities, coupled
      with the results of the specific table tennis tests indicate that: a)
      subcutaneous fatty tissue on the lower extremities significantly limits the test
      results where movements involving fast changes in direction are required; b)
      subcutaneous abdominal adipose tissues have a positive influence on tasks
      demanding controlled and precise alternate bouncing of the ball; c) in general, a
      positive influence can be seen in the results of specific tests concerning the
      following motor abilities: arm coordination, agility, explosive arm power,
      movement frequency speed and repetitive leg power. The test used for a
      coordination assessment of the whole body revealed a negative influence on the
      success of performing specific tasks.

PMID- 24851625
TI  - Effect of exercises on quality of life in women with osteoporosis and osteopenia.
AB  - Osteoporosis is a disease characterized by decreased bone mass and impaired
      microarchitecture resulting in bone fragility and an increased risk of fractures.
      Prevention of osteoporosis and osteoporotic fractures among others include
      adequate physical activity. Epidemiological studies indicate that fewer fractures
      in active women, regardless of whether it is a result of direct effects on bone
      or improve coordination, balance and muscle strength. The aim of research was to
      examine the impact of exercise program for osteoporosis in the duration of four
      weeks on health and psychological aspects of patient quality of life using the
      questionnaire SF-36, used before and after the program. The SF-36 is used for
      self-assessment of health status and represents the operationalization of two
      general concept of health such as physical and mental health and consists of 36
      particles. The study included 39 participants with osteopenia and osteoporosis.
      All respondents have implemented a program of exercises for osteoporosis in
      duration 28 days. The program consisted of exercises for osteoporosis, advice on
      diet, tips on preventing falls, interviews and examinations performed before and
      during implementation of the program. Results showed that using a short program
      of exercises and education leads to significant changes in self-reported quality
      of life of subjects. The study confirmed a statistically significant reduction in
      pain using a visual analog scale (VAS) before and after the program.

PMID- 24851626
TI  - Jaw injuries of independence victims from the 1991 War in Croatia.
AB  - In the aetiology of maxillofacial injuries, car accidents, violence, sports
      injuries and lately war injuries are frequently mentioned. The purpose of this
      study was to exhibit and analyse types of jaw injuries on bodies exhumed from
      massive and individual graves located in regions temporarily occupied during the
      War in Croatia that lasted from 1991 to 1995. The sample was the post-mortal
      documentation of the orofacial region (set of teeth, photographs, radiographic
      images) of 1068 victims exhumed from massive grave sites in Croatia. The jaw
      traumatism was analysed on the whole sample as well as on individual graves,
      whilst the analysis of trauma frequency was performed separately. Descriptive
      statistics were computed and the value of P < .05 was accepted as statistically
      significant. Results of this study showed that out of 1068 examined corpses, 332
      had midface and lower face fractures, which was 31.1% of the total number. Lower
      face fractures were more frequent with 28.1%. Age related frequency analysis
      showed a significant dependency. There were 34.6% of fractures in the under 30
      age group, 34.2% in those aged 30-60, while 21.3% of fractures were noted in the
      over 60 age group. Female bodies had the lowest number of jaw fractures
      regardless of the osteoporotic changes. The results of this study suggest that
      younger and middle aged persons were molested more. Jaw fractures suggest ante
      mortal molestation. In females, the more likely fracture causes were the falls of
      the bodies into the graves or body to body hits.

PMID- 24851627
TI  - Oral health-related risk behaviours and attitudes among Croatian adolescents-
      multiple logistic regression analysis.
AB  - The aim of this study was to explore the patterns of oral health-related risk
      behaviours in relation to dental status, attitudes, motivation and knowledge
      among Croatian adolescents. The assessment was conducted in the sample of 750
      male subjects - military recruits aged 18-28 in Croatia using the questionnaire
      and clinical examination. Mean number of decayed, missing and filled teeth (DMFT)
      and Significant Caries Index (SIC) were calculated. Multiple logistic regression
      models were crated for analysis. Although models of risk behaviours were
      statistically significant their explanatory values were quite low. Five of them-
      rarely toothbrushing, not using hygiene auxiliaries, rarely visiting dentist,
      toothache as a primary reason to visit dentist, and demand for tooth extraction
      due to toothache--had the highest explanatory values ranging from 21-29% and
      correctly classified 73-89% of subjects. Toothache as a primary reason to visit
      dentist, extraction as preferable therapy when toothache occurs, not having
      brushing education in school and frequent gingival bleeding were significantly
      related to population with high caries experience (DMFT > or = 14 according to
      SiC) producing Odds ratios of 1.6 (95% CI 1.07-2.46), 2.1 (95% CI 1.29-3.25), 1.8
      (95% CI 1.21-2.74) and 2.4 (95% CI 1.21-2.74) respectively. DMFT> or = 14 model
      had low explanatory value of 6.5% and correctly classified 83% of subjects. It
      can be concluded that oral health-related risk behaviours are interrelated. Poor
      association was seen between attitudes concerning oral health and oral health
      related risk behaviours, indicating insufficient motivation to change lifestyle
      and habits. Self-reported oral hygiene habits were not strongly related to dental
      status.

PMID- 24851628
TI  - The incidence of satellite cysts in keratocystic odontogenic tumors.
AB  - Renaming of the Odontogenic Keratocyst as the Keratocystic Odontogenic Tumor by
      the World Health Organization (WHO) is based on the aggressive nature of this
      lesion. Satellite cysts founded in the walls of the original cysts may give rise
      to a new lesion formation. The aim of this retrospecitve study was to identify
      the existence of specific features according incidence of satellite cysts and the
      pallisading of the basal layer of the epithelium and to establish their mutual
      correlation. The histopathologic data of Keratocystic Odontogenic Tumor on the
      basis of new WHO's classification (2005) were analized. Prominent palisade basal
      cell layer was found in 415 (94.75%) and partially absent palisade basal cell
      layer in 23 (5.25%) cases. Satellite cysts were presented in prominent palisade
      basal cell layer in 85 specimens (20.5%) and in cases with partial absent of the
      palisade basal layer in 3 spicemens (13%). The higher the frequency of
      pallisading was the higher the frequency of satellite cysts was (p > 0.05).

PMID- 24851629
TI  - Initial effects of a treatment by fixed partial dentures supported by mini dental
      implants from a patient's point of view.
AB  - Mini dental implants (MDIs) in dentistry are recommended for cases with adequate
      bone quality and height, but a lack of alveolar bone width. Some studies well
      documented successful usage of MDIs for a removable denture support, but studies
      of MDIs supporting fixed prosthodontic restorations are scarce. We aimed to study
      the effect of fixed partial dentures (FPD) therapy supported by MDIs or by MDIs
      and natural teeth, on patients self perceived oral health related quality of life
      (OHRQoL), self perceived oral aesthetics and self perceived chewing function. A
      total of 23 patients (10 female and 13 men, age range from 54 to 78 years) were
      included and 61 MDIs were inserted, 10 in the maxilla and 51 in the mandible. In
      14 patients FPDs were constructed only on MDIs and in 9 patients FPDs were
      constructed on both, MDIs and natural teeth. FPDs on MDIs were replacing mostly
      mandibular incisors, the second maxillary incisors and the first maxillary
      premolars. Those FPDs supported by both, MDIs and natural teeth had some MDIs
      inserted in frontal regions to allow a FPD construction. The three
      questionnaires: the OHIP-CRO14 for the assessment of OHRQoL, the OES-CRO for
      assessment of oral aesthetics and the Chewing function questionnaire (CFQ) for
      assessment of chewing function have been administrated twice:prior to the MDIs
      insertion and three months after the FPD treatment supported by MDIs had been
      finished. The CFQ and the OHIP summary scores significantly decreased revealing
      better OHRQoL and better chewing ability after treatment, and the OES scores
      significantly increased indicating increased self perceived oral aesthetics (p <
      0.01). Clinical examination revealed no periimplant inflammation. Patients' data
      supplement the initially promising clinical findings. However, further follow ups
      will be necessary to finally confirm the long term clinical benefit of MDIs.

PMID- 24851630
TI  - Evaluation of sentinel node biopsy in oral carcinomas.
AB  - It is still a matter of debate whether sentinel node biopsy might replace neck
      dissection in patients with clinically negative neck lymph nodes who suffer from
      oral squamous cell carcinoma. In 30 patients (26 male, 4 female, average age 59.4
      years) with oral squamous cell carcinoma we performed ultrasound guided punction
      of the lymph nodes which were lymphoscintigraphically seen together with
      histopatological analysis of the dissected node. Sentinel lymph node was seen in
      93% cases. By use of lymphoscintigraphy sentinel node was verified in 23
      patients. Ultrasound guided punction showed presence of regional disease in 10%
      of cases, whereas sentinel biopsy revealed 23 of the converted necks.
      Histopathological findings were positive in 33% of our patients. The results of
      this study revealed that sentinel biopsy did not reveal 27% of the patients with
      positive neck histopathology. In conclusion, sentinel node biopsy should be
      performed in selective cases as in some localizations it is easier to perform
      neck dissection in comparison to the sentinel node biopsy.

PMID- 24851631
TI  - Full thickness cartilage palisade tympanoplasty with malleus interposition: a
      study of the long term results.
AB  - The aim of this retrospective study is to review long term results of full
      thickness cartilage palisade tympanoplasty (FTCPT) with malleus head
      interposition performed on 51 patients (56 ears); 36 women and 15 men (7-73
      years, 44 years average). The pathology of ears which encourages this technique
      of tympanoplasty is presented. On average 12 years after surgery we have
      elaborated anatomic and functional results. Anatomic results were categorized
      based on empiric evaluation of the new tympanic membrane status: 40 (71%)
      tympanic membranes without anatomic irregularities, 14 (25%) with irregularities
      and 2 (4%) with secondary perforation. Functional results (tonal audiogram) are
      based on pure tone average air-bone gap (PTA-ABG) at 4 frequencies. Main
      functional results of 51 ears (51 audiograms performed): pre- and post-operative
      average PTA-ABGs were 27.07 +/- 9.98 and 10.77 +/- 7.85 dB (t = 10.36; p <
      0.001). In the group of ears with a tympanic membrane with no anatomic
      irregularities, pre- and post-operative average PTA-ABGs were 27.30 +/- 10.56 and
      10.82 +/- 8.33 dB (t = 8.09; p < 0.001). In the group of ears with cartilage
      resorption, pre- and post-operative PTA-ABGs were 24.92 +/- 8.19 and 9.33 +/-
      6.58 dB (t = 6.21; p < 0.001). The differences between the two groups are
      irrelevant. Postoperative PTA-ABG values of ears after first surgery (N = 34) and
      revision surgery (N = 17) was significantly different (8.75 +/- 5.75 and 15.16 +/
      9.62 dB) (t = 2.60; p = 0.016). In spite of the thickness of the new tympanal
      membrane, FTCPT is a successful technique for solving advanced ear pathology.

PMID- 24851632
TI  - Opportunities and contradictions in maritime heritage and small-scale fishing--a
      case study of Catalonia.
AB  - Much has been written in recent years about the crisis in fisheries caused by the
      critical reduction in catches and about the strategies developed by local
      communities of fishers in response. The aim of this article is to demonstrate
      that the use of maritime heritage can also be considered part of these
      strategies. Like fishers elsewhere, Catalan small-scale fishers face severe
      threats to their professional survival. Recently some of them have became
      involved in activities related to maritime heritage as a strategy to draw the
      attention of policy makers and the general public to their problems, a strategy
      not without clear contradictions. But beyond these contradictions, the article
      points out the opportunities that use of maritime heritage offers to fishers in
      Catalonia as well as elsewhere.

PMID- 24851633
TI  - The discrepancy in the perception of the public-political speech in Croatia.
AB  - Key place in this paper takes the study of political speech in the Republic of
      Croatia and their impact on voters, or which keywords are in political speeches
      and public appearances of politicians in Croatia that their voting body wants to
      hear. Given listed below we will define the research topic in the form of a
      question - is there a discrepancy in the perception of the public-political
      speech in Croatia, and which keywords are specific to the two main regions in
      Croatia and that inhabitant these regions respond. Marcus Tullius Cicero, the
      most important Roman orator, he used a specific associative mnemonic technique
      that is called "technique room". He would talk expound on keywords and conceptual
      terms that he needed for the desired topic and join in these make them, according
      to the desired order, in a very creative and unique way, the premises of the
      house or palace, which he knew well. Then, while holding the speech intended to
      pass through rooms of the house or palace and then put keywords and concepts come
      to mind, again according to the desired order. Given that this is a specific kind
      of research political speech that is relatively recent in Croatia, it should be
      noted that there is still, this kind of political communication is not
      sufficiently explored. Particularly the emphasis on the impact and use of
      keywords specific to the Republic of Croatia, in everyday public and political
      communication. The paper will be analyzed the political, campaign speeches and
      promises several winning candidates, and now Croatian MEPs, specific keywords
      related to: economics, culture, science, education and health. The analysis is
      based on comparison of the survey results on the representation of key words in
      the speeches of politicians and qualitative analysis of the speeches of
      politicians on key words during the election campaign.

PMID- 24851634
TI  - Pagan-Christian change in northeastern Hungary in the 10th-13th centuries AD--a
      palaeodemographic aspect.
AB  - In the present paper the authors compared skeletal populations (2421 individuals)
      excavated from four cemeteries, namely Hajdudorog-Gyulas (10th century AD),
      Hajdidorog-Temetohegy (11th century AD), Hajdudorog-Katidulo (12th-13th century
      AD) and Hajdudorog-Szalldafold (12th-13th century AD) from a micro-region of
      Northern Hajdusag (located in the northern part of the Great Hungarian Plain in
      Hungary in the Carpathian Basin) based on demographic data. The cemeteries were
      dated to the age of the Hungarian conquest and the Arpadian age and provided
      representative data for anthropological research. Previous studies based on
      craniological and archaeological investigations have already suggested that there
      was discontinuity in the population history between the 10th and the 11th
      centuries AD and continuity between the 11th and 12th centuries AD in this
      region. This hypothesis could be partially supported by demographic
      investigations because conclusive evidence was found that there must have been a
      change in the population at the turn of the 10th and 11th centuries AD, and there
      was certain continuity between the 11th and 12-13th centuries AD. The authors
      suppose that there were two crises in the examined period: the first crisis set
      in at the transition from the pagan era (10th century AD) to the Christian era
      (from the beginning of the 11th century AD, with population resettlements within
      the Carpathian Basin), the second might have been more moderate and meant burying
      the dead of the populations lacking a church in the churchyards of villages which
      had a church. At that time one graveyard around a church may have been used by
      several village populations.

PMID- 24851635
TI  - De novo case of a partial trisomy 4p and a partial monosomy 8p.
AB  - The extent of clinical expression in cases of segmental aneuploidy often varies
      depending on the size of the chromosomal region involved. Here we present
      clinical and cytogenetic findings in a 5-month old boy with a duplication of a
      chromosomal segment 4p16.1-->4pter and a deletion of a chromosomal segment 8p23.1
      ->8pter. His karyotype was determined by applying classical GTG banding and FISH
      method (WHCR region, centromere 4, centromere 8, telomere 8p) as
      46,XY,der(8)t(4;8)(p16.1;p23.1).ish der(8)t(4;8)(D8S504-,WHCR+,D8Z2+)dn. Parents
      are not related and have normal karyotypes, indicating de novo origin. We have
      compared similarity of the clinical features in our proband to other patients
      carrying only a duplication of the distal part of 4p or a deletion of distal part
      of 8p or similar combination described in the literature.

PMID- 24851636
TI  - Use of recombinant human bone morphogenetic protein (rhBMP2) in bilateral
      alveolar ridge augmentation: case report.
AB  - In recent years, the delivery of osteoinductive factors such as bone morphogenic
      proteins (BMPs) has become an alternative approach to traditional bone grafting
      due to their capacity to produce bone healing and new bone formation. BMP-2 has
      proved to possess the highest osteoinductive potential among BMPs. The case
      reported the clinical use of recombinant human BMP-2 for bilateral vertical
      alveolar ridge augmentation. In a case of 61 year-old patient with a significant
      bilateral vertical bony deficiency of the mandible, rhBMP-2 administered via an
      absorbable collagen sponge carrier (ACS) was used for bilateral alveolar ridge
      bone induction. Augmented sites were covered and fixed with titanium mesh.
      Augmented sites were reopened 6 months after surgery. Titanium membrane and
      retaining screws were removed and three dental implants were placed. The tissue
      samples for the histologic analysis were harvested. Following 3 months healing
      period, the submerged implants were uncovered and restored with zirconium-ceramic
      crowns. Cone beam computed tomography (CBCT), panoramix and 3D radiographic
      evaluation were obtained prior to and after the surgical procedure. Vertical gain
      of the bone was 5.5 mm on the left and 5 mm on the right side, with 6 mm width of
      the bone. Histologic analysis revealed formation of mature trabecular bone with
      signs of osteoblastic proliferation. Implant stability quotient (ISQ) values were
      in the range between 69 and 75 for all three implants. No suppuration, gingival
      recession or pain were present 24 months after surgery. Vertical bone
      augmentation using rhBMP-2 is optional treatment modality to consider when
      planning dental implant placement in sites where severe vertical insufficiency
      exists.

PMID- 24851637
TI  - Asymmetric neonatal crying: microdeletion, infection or birth injury?--a case
      report.
AB  - Asymmetric neonatal crying is a rare minor congenital abnormality caused by
      unilateral agenesis or hypoplasia of depressor anguli oris muscle and depressor
      labii inferioris muscle. It is either an isolated clinical finding or one of the
      clinical findings included in several malformation syndromes linked to a
      microdeletion within a chromosomal region 22q11.2. Some malformations in that
      region are associated with serious cardiovascular anomalies. Nowadays, standard
      diagnostic techniques for detecting aberrations within the chromosomal region
      22q11.2 are fluorescence in situ hybridization (FISH) and multiplex ligation
      probe amplification (MLPA). This short report describes an eutrophic female
      newborn whose both lip corners are symmetrically positioned while at rest; while
      crying, left lip corner and left half of the lower lip are falling. She also has
      partial bilateral syndactyly between second and third toe, open foramen ovale and
      by ultrasound detected hyperechogenic region in the thalamus and brain
      parenchyme. Aiming to investigate etiopathogenesis of the newborn asymmetric
      crying and accompanying minor abnormalities, we have tried to verify or exclude:
      microdeletion syndrome, TORCH infection and birth injury. Recognising such a
      paresis soon after the delivery is of great importance and can be helpful in
      detecting other accompanying anomalies, especially cardiovascular anomalies.

PMID- 24851638
TI  - A case of transient constrictive pericarditis in a 42-year-old patient.
AB  - We report a case of 42 year old patient with acute idiopathic pericarditis in
      whom we describe transient cardiac constriction, consisting of the temporary
      development of features of constrictive pericarditis with subsequent return to
      normality after medical therapy alone. After a mean of 6 months, there have been
      no recurrences of constrictive physiology or clinical symptoms. The results of
      our study suggest that patients who have constrictive features early in the
      course of their illness and are hemodynamically stable should be considered for a
      trial of conservative therapy before pericardiectomy is pursued.

PMID- 24851639
TI  - Ovarian torsion in adolescent with chronic immune thrombocytopenia.
AB  - Ovarian torsions in adolescence are rarity, particularly bilateral, with mostly
      unknown etiology. Enlargement of the ovary contributes to torsion. Young girl
      presenting with abdominal pains, nausea and vomiting was for two days suspected
      and observed as gastroenteritis. By exclusion of gastroenteritis she was admitted
      for gynecological work-up. Ultrasound showed significantly enlarged right ovary,
      with tumor-like appearance. At the laparotomy, gynecologist found torsioned,
      necrotic ovary and ovariectomy was performed. Histology showed massive stromal
      bleeding (haemorrhage). Asymptomatic enlargement of remaining ovary occurred nine
      months after the ovariectomy. This enlargement was accompanied with platelets'
      fall and the possibility of repeated torsion impended. Thrombocytopenia was
      suspected from the first moment, but diagnosed after the surgery.
      Thrombocytopenia in adolescence requires additional attention as possible cause
      of intra-ovarian bleeding with consecutive enlargement and may lead to torsion.
      Oral contraceptives regulate dysfunctional bleeding, decrease ovarian volume and
      by so, may minimize risk of torsion. This strategy proved effective in the case
      we present.

PMID- 24851640
TI  - A first case of endoscopical removal of an eroded adjustable gastric band in
      Croatia.
AB  - Laparoscopic gastric banding (LAGB) is one of the most common surgical procedures
      in the treatment of morbid obesity since it provides good long-term outcomes in
      weight loss and decrease of comorbidities associated with obesity. Although the
      procedure has low morbidity and almost none-existing mortality, certain
      complications can occur. Erosion of the band into the gastric wall is one of the
      rare complications in LAGB. The reported incidence varies from 1 to 11%, however
      the largest study reported an incidence of 1.6%. This is in accordance with the
      incidence in our Centre for obesity, where only one case of erosion occurred
      among 112 operative procedures. The aim of this paper is to present a patient
      with gastric band erosion and it's removal by using the endoscopic techniques as
      a minimally invasive management method.

PMID- 24851641
TI  - Development of the competitive business in the context of environmental
      legislation in Croatia.
AB  - Environmental protection has a key role in the context of crisis management. It
      is not just about development of the industry of environmental protection and
      implementation of new ways of management in innovative solutions in solving
      problems. Important area of improvement is also revision of environmental
      legislation aiming at simplification and reduction of costs of procedures for the
      business. This paper discusses problems of business sector in Croatia related to
      transposition of demanding environmental EU regulation, it suggests improvements
      such as simplification of special waste management systems, of environmental
      impact assessments processes, environmental permitting etc. The paper considers
      revision of environmental protection not by lowering environmental standards, but
      by introducing transparent and compromising models between business and
      environmental protection, based on sustainable development, with control
      mechanisms which don't impact functioning of business sector (and its
      competitiveness), therefore allowing successful protection of environment and its
      renewable and non-renewable resources.

PMID- 24851642
TI  - Green technologies--assumption of economic recovery.
AB  - Green technologies include implementation of technological projects in the field
      of environmental protection through all associated components, such as: waters,
      soil, air or biodiversity. Hence, such projects potentially become a driving
      force of new economic momentum in the conditions of post-crisis recovery. In
      addition, the support of this segment by the institutions of the European Union,
      either in terms of organization through the establishment of rules and systems
      for monitoring and control of environmental protection measures, and most
      importantly in terms of finances, by supporting the development of infrastructure
      for environmental protection, is today an indisputable category. The aim of the
      research is to show the potential of green technologies in the initiation of
      economic activities based on content analysis of the collected literature, as
      well as to determine the correlation between green technologies and environmental
      protection and the measures for the reduction of the impact of energy sector on
      the greenhouse gas emissions.

PMID- 24851643
TI  - Brugada syndrome and right ventricle morphofunctional abnormalities on
      echocardiography in young male with family anamnesis of sudden cardiac death.
AB  - First presented by Brugada and Brugada in 1992, Brugada Syndrome (BrS) is a
      primary electrical disease of the heart that causes sudden cardiac death or life
      threatening ventricular arrhythmias. This disease is hereditary autosomic
      dominant transmitted and genetically determined. The syndrome has been linked to
      mutations in SCN5A, the gene encoding for the a-subunit of the sodium channel.
      Electrocardiogram (ECG) abnormalities indicating Brugada syndrome, include
      repolarization and depolarization abnormalities in the absence of identifiable
      structural cardiac abnormalities or other conditions or agents known to lead to
      ST-segment elevation in the right precordial leads (V1-V3). Intravenous
      administration of sodium channel blocking drugs may modify the ECG pattern.
      Ajmaline, flecainide, procainamide and propafenone exaggerate the ST-segment
      elevation or unmask it when it is initially absent. An implantable cardioverter
      defibrillator (ICD) is the only proven effective device treatment for the
      disease. Although BrS is primary electrical disease, some authors have suggested
      the presence of morphological and functional abnormalities mainly located in the
      right ventricle (RV), notably in the outflow tract (RVOT). In this short report
      we will present a young male, with predisposition and positive family history of
      sudden cardiac death, with complete diagnostic procedure including propafenon
      testing unmasking Brugada syndrome. An echosonography revealed dilated apical
      right ventricle, suggesting BrS is not only electrical disorder, but may include
      morphofunctional abnormalities, described in previous reports. In addition, we
      reviewed the possible connection between Brugada syndrome and morphological
      abnormalities in RV.

PMID- 24851644
TI  - Effects of internal and external environment on health and well-being: from cell
      to society.
AB  - Stem cell fate in cell culture depends on the composition of the culturing media.
      Every single cell in an organism is influenced by its microenvironment and
      surrounding cells. Biology, psychology, emotions, spirit, energy, lifestyle,
      culture, economic and political influences, social interactions in family, work,
      living area and the possibilities to expresses oneself and live full life with a
      sense of well-being have influence on people appearances. Disease is as much
      social as biological. It is a reaction of an organism to unbalancing changes in
      the internal environment caused by the changes in the external environment and/or
      by the structural and functional failures or unfortunate legacies. Health
      gradient in the society depends on the every day circumstances in which people
      live and work. The health of the population is an insight into the society. The
      problem facing medicine in the complex society of today cannot be resolved
      without the aid of social sciences, as cultural, social, ecological and mental
      processes affect physiological responses and health outcomes. Anthropology could
      be a bridge between biomedicine and social sciences and influence strategies in
      public health to prevent rather than cure and in education for fulfillment in
      life and improvement of society.

PMID- 24851645
TI  - Advances in a rapidly emerging field of hair follicle stem cell research.
AB  - Human skin maintains the ability to regenerate during adulthood, as it constantly
      renews itself throughout adult life, and the hair follicle (HF) undergoes a
      perpetual cycle of growth and degeneration. The study of stem cells (SCs) in the
      epidermis and skin tissue engineering is a rapidly emerging field, where advances
      have been made in both basic and clinical research. Advances in basic science
      include the ability to assay SCs of the epidermis in vivo, identification of an
      independent interfollicular epidermal SC, and improved ability to analyze
      individual SCs divisions, as well as the recent hair organ regeneration via the
      bioengineered hair follicular unit transplantation (FUT) in mice. Advances in the
      clinic include recognition of the importance of SCs for wound repair and for gene
      therapy in inherited skin diseases, for example epidermolysis bullosa. The study
      of the HF stem cells (HFSCs) started by identification of epidermal SC in the HF
      bulge as quiescent "label retaining cells". The research of these cells emerged
      rapidly after the identification of bulge cell molecular markers, such as keratin
      15 (K15) and CD34 in mice and CD200 in humans, which allowed the isolation and
      characterization of bulge cells from follicles. This paper provides an overview
      of the current knowledge on epidermal SCs in the HF describing their essential
      characteristics and the control of follicle SCs fate, their role in alopecia, as
      well as their use in tissue engineering.

PMID- 24851646
TI  - Ulipristal acetate in emergency contraception.
AB  - Despite the widespread availability of highly effective methods of contraception,
      unintended pregnancy is common. Unplanned pregnancies have been linked to a range
      of health, social and economic consequences. Emergency contraception reduces risk
      of pregnancy after unprotected intercourse, and represents an opportunity to
      decrease number of unplanned pregnancies and abortions. Emergency contraception
      pills (ECP) prevent pregnancy by delaying or inhibiting ovulation, without
      interfering with post fertilization events. If pregnancy has already occurred,
      ECPs will not be effective, therefore ECPs are not abortificants. Ulipristal
      acetate (17alpha-acetoxy-11beta-(4N-N,N-dymethilaminophenyl)-19-norpregna--4,9
      diene-3,20-dione) is the first drug that was specifically developed and licensed
      for use as an emergency contraceptive. It is an orally active, synthetic,
      selective progesterone modulator that acts by binding with high affinity to the
      human progesterone receptor where it has both antagonist and partial agonist
      effects. It is a new molecular entity and the first compound in a new
      pharmacological class defined by the pristal stem. Up on the superior clinical
      efficacy evidence, UPA has been quickly recognized as the most effective
      emergency contraceptive pill, and recently recommended as the first prescription
      choice for all women regardless of the age and timing after intercourse. This
      article provides literature review of UPA and its role in emergency
      contraception.

PMID- 24851647
TI  - Should MS be treated by escalation or induction therapy?
AB  - MS is a chronic, increasingly disabling disease whose long-term outcomes
      determine the key social, medical and economic impact of this disease. Disease
      modifying therapies (DMTs) for multiple sclerosis (MS) are prescribed to delay
      disease progression and to protect a patient's functional capability. The
      concepts of escalation and induction immunotherapy in MS represent different
      therapeutic strategies for the treatment of MS. Both strategies may be valuable
      options for patients starting on DMT, however, induction therapy mainly focuses
      on patients with very aggressive course of MS from the onset. Using a patient
      unique approach to selection of treatment, MS can be effectively control disease
      and may delay or even prevent the development of secondary progressive MS.

PMID- 24851648
TI  - 'Lege artis'--an outdated concept in modern medicine?

PMID- 24851649
TI  - Human rights and reproductive choices in the case-law of Italian and European
      courts.
AB  - The major issues regarding human fertilisation and embryology are addressed in a
      comparative perspective and in the light of relevant rulings of the European
      Court for Human Rights: the relationship between artificial procreation and
      parental responsibilities, the legal nature of the unborn child, the human right
      to reproduce and to have a healthy child. The article focuses on the key data of
      the latest Italian regulation regarding assisted conception, especially compared
      with British law. Particular attention is paid to the contribution given by
      recent European decisions to the protection of new human rights. National and
      international judgements ensure the right to private life and to health that are
      not always guaranteed by law. Converging developments in case-law panorama make
      the right to have children, to responsible procreation, to information about
      medical treatments, much less disharmonic realities than the Member States
      legislation suggests.

PMID- 24851650
TI  - The possibility of compensation for damages in cases of wrongful conception,
      wrongful birth and wrongful life. An Estonian perspective.
AB  - While case law in cases of wrongful conception, wrongful birth and wrongful life
      is completely missing in Estonia, this article is aimed at providing possible
      solutions under Estonian law to some of the legally complex problems that these
      cases contain. Through the analysis of Estonian, German and U.S. legal literature
      and case law, the article is mainly focused on proposing some solutions to the
      legal problems concerning compensable damage, but also explains the Estonian
      legal framework of the contractual and delictual basis for compensation for the
      damages. The application of several grounds for the possibility of limiting the
      compensation in the afore-mentioned cases are analysed.

PMID- 24851651
TI  - The case of the electronic cigarette in the EU.
AB  - Although the electronic cigarette was invented in 2004, only recently the product
      has started to provoke discussion. On the one hand, the electronic cigarette is
      characterized by scientific uncertainties. It is not clear whether the device can
      be used in smoking cessation therapy, whether the use induces non-smokers-
      including minors--to start smoking and whether the vaporized substances and the
      act of vaporizing itself (which is smoking an electronic cigarette) is harmful.
      On the other hand, there is no harmonised European legal framework and different
      Member States attribute a different legal status to the e-cigarette. In this
      article, the author analyses how the e-cigarette should be qualified according to
      the current European legislation and ECJ case law and describes how the e
      cigarette is qualified in the UK, France, The Netherlands, Belgium and Spain.

PMID- 24851653
TI  - European Court of Human Rights. EC HR 2014/4 Case of I.B. v. Greece, 3 October
      2013, no. 552/10 (first section).

PMID- 24851652
TI  - Giving information on medicinal products to the general public--in search of a
      definition to safeguard the patient.
AB  - Information on medicinal products is vital for enabling patients to give informed
      consent to the use of a specific product. Within the European Union (EU) the
      debate about how much information about prescription-only medicinal products
      should be made available to patients has gone on for the past five years with no
      definite conclusion yet. This contribution assesses the current legislation and
      the ongoing debate in order to identify the challenges and the prospect of new
      legislation, and consider its potential implications for the scope for
      advertising and for patient safety.

PMID- 24851654
TI  - European Court of Human Rights. ECHR 2014/5 Case of Glien v. Germany, 28 November
      2013, no. 7345/12 (fifth section).

PMID- 24851655
TI  - European court of Human Rights. ECHR 2014/6 Case of Arskaya v. Ukraine, 5
      December 2013, no. 45076/05 (fifth section).

PMID- 24851656
TI  - European Court of Human Rights. ECHR 2014/7 Case of Raudevs v. Latvia, 17
      December 2013, no. 24086/03 (fourth section).

PMID- 24851658
TI  - European Court of Justice. ECJ 2014/4 Susanne Sokoll-Seebacher v. Agnes
      Hemetsberger, successor to Susanna Zehetner, 13 February 2004 (C367/12).

PMID- 24851657
TI  - European Court of Justice. ECJ 2014/3 Alessandra Venturini v. ASL Varese and
      others (C-159/12), Maria Rosa Gramegna v. ASL Lodi and others (C-160/12) and Anna
      Muzzio v. ASL Pavia and others (C-161/12) of 5 December 2013.

PMID- 24851659
TI  - Instrument development and testing.

PMID- 24851660
TI  - Development of the Intrapartum Nurses' Beliefs Related to Birth Practice Scale.
AB  - BACKGROUND AND PURPOSE: Intrapartum (IP) nurses make decisions driven by beliefs.
      This study's purpose was to develop an instrument measuring birth beliefs of the
      IP nurse related to birth practice. METHODS: The theory of planned behavior
      guided the development process, providing a connection between beliefs and
      practice. This article describes the domain identification, item generation, and
      instrumentation process. RESULTS: The Intrapartum Nurses' Beliefs Related to
      Birth Practice (IPNBBP) is an online, self-administered instrument with 36 Likert
      scale items measuring the birth beliefs of IP nurse and categorizes medicalized
      birth beliefs, normal birth beliefs, and beliefs outlined in the theory of
      planned behavior. CONCLUSION: Following psychometric testing, the IPNBBP may be
      used to provide a link between the beliefs and practice of IP nursing and
      maternal and neonatal outcomes.

PMID- 24851661
TI  - Development and testing of the Preeclampsia Prenatal Symptom-Monitoring Checklist
      (PPSMC).
AB  - BACKGROUND AND PURPOSE: Preeclampsia, a common disorder of unknown origin,
      presents with signs and symptoms that can be subtle, making assessment and
      intervention challenging. The purpose of this study was to refine the
      psychometric properties of an instrument designed to assess a comprehensive range
      of preeclampsia symptoms. METHODS: Testing of the Preeclampsia Prenatal Symptom
      Monitoring Scale (PPSMC) was accomplished through a retrospective, correlational,
      and comparative study of 100 postpartum women with preeclampsia and gestational
      hypertension. RESULTS: The initial 17-item Cronbach's alpha was .73; reliability
      of the current 11-item PPSMC increased to .77. Content validity index for the
      PPSMC (17 items) was .88; for the PPSMC (11 items), .93. Exploratory factor
      analysis, known group comparisons, and predictive validity lend beginning support
      of the instrument's construct validity. CONCLUSION: This instrument may be useful
      in examining in greater detail the symptomatology of women with preeclampsia in
      practice and research settings.

PMID- 24851662
TI  - Measuring the meaning of miscarriage: revision of the Impact of Miscarriage
      Scale.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to determine a factor
      structure for the Impact of Miscarriage Scale (IMS). The 24 items comprising the
      IMS were originally derived from a phenomenological study of miscarriage in
      women. Initial psychometric properties were established based on a sample of 188
      women (Swanson, 1999a). METHOD: Data from 341 couples were subjected to
      confirmatory factor analysis (CFA) and exploratory factor analysis (EFA).
      RESULTS: CFA did not confirm the original structure. EFA explained 57% of the
      variance through an 18-item, 4-factor structure: isolation and guilt, loss of
      baby, devastating event, and adjustment. Except for the Adjustment subscale,
      Cronbach's alpha coefficients were > or = .78. CONCLUSION: Although a 3-factor
      solution is most defensible, with further refinement and additional items, the
      4th factor (adjustment) may warrant retention.

PMID- 24851663
TI  - A child self-report exemplar: adapting administration procedures of the self
      perception profile for children to reduce measurement error.
AB  - BACKGROUND AND PURPOSE: Child self-reports can provide unique information to
      researchers. When the 2-step structured format of a frequently used self-concept
      measure resulted in unusable data during a pilot of inner-city school children,
      the framework of attention and executive control was used to analyze the task and
      adapt administration format. METHODS: A card system was substituted for the paper
      format and Cronbach's alphas calculated on data obtained from 233 3rd-6th
      graders. RESULTS: Complete data; alphas ranged from .58 (social competence) to
      .75 (behavioral conduct). CONCLUSIONS: The use of cards to facilitate choices
      effectively reduced error by removing one option from view prior to completing
      second step. Two competence subscales (social and athletic) had alphas less than
      .70 suggesting further exploration with this population.

PMID- 24851664
TI  - The new Intragroup Conflict Scale: testing and psychometric properties.
AB  - BACKGROUND AND PURPOSE: The importance of healthy work environments has received
      attention. Health care organizations are plagued with conflict which is
      detrimental to work environments. Thus, conflict must be studied. The purpose of
      this article is to describe the testing of a measure of conflict. METHODS: A
      survey was used to evaluate the psychometric properties. The sample consisted of
      430 nurses at an academic medical center. RESULTS: Using principal component
      analysis (PCA) with varimax rotation, a six-factor solution (30 items) that
      explained 74.3% of variance emerged. Coefficient alpha ranged from .95 to .81.
      Correlations with existing scales supported construct validity (r = -.32(-)-.58).
      CONCLUSIONS: The results are encouraging. Use of the scale may provide insight
      into the impact of conflict on patient, staff, and organizational outcomes.

PMID- 24851665
TI  - A meta-synthesis of health-related self-efficacy instrumentation: problems and
      suggestions.
AB  - BACKGROUND AND PURPOSE: Self-efficacy, a central construct in health
      interventions, has been measured in various contexts. The absence of any
      published meta-review of self-efficacy instrumentation led to the current meta
      synthesis that reports and evaluates the instrumentation processes. METHODS: A
      systematic search resulted in 39 self-efficacy instrumentation studies, which
      were evaluated for the aspects of conceptual bases, health contexts, operational
      definition, instrumentation procedures, reliability and scale length, and item
      content. RESULTS: Primarily based in Bandura's social cognitive theory, these
      studies reported self-efficacy instrumentation for developing new scales and
      modifying/validating measures for illness management, healthy behavior
      adoption/maintenance, disease/risk prevention, and aging management. Trait-like,
      specific-domain, and situation approaches were used for generating item content.
      Problems in some studies include non-efficacy items, a lack of systematic
      instrumentation procedures, item content too general for specific-domain self
      efficacy, and measurement inefficiency. CONCLUSIONS: The piecemeal fashion of
      self-efficacy instrumentation has resulted in incomparable self-efficacy measures
      of similar domains of health functioning. A trans-domain framework, thus, is
      warranted. Suggestions are provided for solving other problems in self-efficacy
      instrumentation.

PMID- 24851666
TI  - Postexamination analysis of objective tests using the three-parameter item
      response theory.
AB  - BACKGROUND AND PURPOSE: Although the importance of item response theory (IRT) has
      been emphasized in health and medical education, in practice, few
      psychometricians in nurse education have used these methods to create tests that
      discriminate well at any level of student ability. The purpose of this study is
      to evaluate the psychometric properties of a real objective test using three
      parameter IRT. METHODS: Three-parameter IRT was used to monitor and improve the
      quality of the test items. RESULTS: Item parameter indices, item characteristic
      curves (ICCs), test information functions, and test characteristic curves reveal
      aberrant items which do not assess the construct being measured. CONCLUSIONS: The
      results of this study provide useful information for educators to improve the
      quality of assessment, teaching strategies, and curricula.

PMID- 24851667
TI  - Development and testing of the Clinical Research Appraisal Inventory-Short Form.
AB  - BACKGROUND AND PURPOSE: The National Academy of Sciences stressed the need for a
      doctorally prepared workforce and earlier entry into doctoral study in nursing
      and the behavioral, social, and basic sciences. Social Cognitive Career Theory
      (SCCT) suggests that self-efficacy for career related skills informs career
      choices. Thus, increasing clinical research self-efficacy early in students'
      studies could increase their choice of a research career. To test interventions,
      a psychometrically sound measure of clinical research self-efficacy is needed.
      METHODS: We examined the psychometrics of the Clinical Research Appraisal
      Inventory-Short Form (CRAI-SF) in undergraduate and first-year graduate students
      (N = 268). This scale is a modification of the Clinical Research Appraisal
      Inventory, which measures physician-scientists' clinical research self-efficacy.
      RESULTS: Content validity was supported by external review. Factor analysis
      revealed six factors explaining 75% of scale variance. Internal consistency of
      subscales and total scale ranged from .84 to .98. Differences in scores by gender
      (p = .016) and discipline of study (p = .000) supported construct validity.
      CONCLUSIONS: The CRAI-SF is a useful measure of undergraduate and first-year
      graduate students' perceived clinical research self-efficacy.

PMID- 24851668
TI  - Development and validation of a survey to assess patient-perceived medication
      knowledge and confidence in medication use.
AB  - BACKGROUND AND PURPOSE: The primary objective of this study is to establish the
      validity and reliability of a perceived medication knowledge and confidence
      survey instrument (Okere-Renier Survey). METHODS: Two-stage psychometric analyses
      were conducted to assess reliability (Cronbach's alpha > .70) of the associated
      knowledge scale. To evaluate the construct validity, exploratory and confirmatory
      factor analyses were performed. RESULTS: Exploratory factor analysis (EFA)
      revealed three subscale measures and confirmatory factor analysis (CFA) indicated
      an acceptable fit to the data (goodness-of-fit index [GFI = 0.962], adjusted
      goodness-of-fit index [AGFI = 0.919], root mean square residual [RMR = 0.065],
      root mean square error of approximation [RMSEA] = 0.073). A high internal
      consistency with Cronbach's a of .833 and .744 were observed in study Stages 1
      and 2, respectively. CONCLUSIONS: The Okere-Renier Survey is a reliable
      instrument for predicting patient-perceived level of medication knowledge and
      confidence.

PMID- 24851669
TI  - Development and psychometric testing of the Mariani Nursing Career Satisfaction
      Scale.
AB  - BACKGROUND AND PURPOSE: The Mariani Nursing Career Satisfaction Scale (MNCSS) was
      developed to explore the influence of mentoring on career satisfaction of
      registered nurses (RNs). A review of the literature revealed no contemporary
      valid and reliable measure of career satisfaction. METHODS: The MNCSS is a
      semantic differential of 16 opposite adjective pairs on which participants rate
      feelings about their nursing career. The MNCSS was used in a pilot study and
      three major studies exploring career satisfaction of RNs. Validity, reliability,
      and exploratory factor analysis (FA) were computed to explore the internal
      structure of the instrument. RESULTS: The newly developed instrument had a
      content validity index (CVI) of .84 and Cronbach's alpha internal consistency
      reliabilities of .93-.96 across three major studies. Exploratory FA (N = 496)
      revealed a univocal instrument with one factor that explains 57.8% of the
      variance in career satisfaction scores. CONCLUSIONS: The MNCSS is a valid and
      reliable instrument for measuring career satisfaction. FA of the combined data
      from three studies yielded one factor that measures the concept of career
      satisfaction.

PMID- 24851670
TI  - Precision of the Conceptual Research Utilization Scale.
AB  - BACKGROUND AND PURPOSE: Conceptual research utilization (CRU) is one indicator of
      an optimum practice environment that leads to improved patient and organizational
      outcomes. Yet, its measurement has not been adequately addressed. In this study,
      we investigated precision of scores obtained with a new CRU scale using item
      response theory (IRT) methods. METHODS: We analyzed the responses from 1,349
      health care aides from 30 Canadian nursing homes using Samejima's (1969, 1996)
      graded response model (GRM). RESULTS: Findings suggest that the CRU scale is most
      precise at low to average trait levels with significantly less precision at
      higher trait levels. CONCLUSIONS: The scale showed acceptable precision at low to
      average trait levels. New items and/or different response options that capture
      higher trait levels are needed. Future development of the scale is discussed.

PMID- 24851671
TI  - Exploratory factor analysis of the Clinical Learning Environment, Supervision and
      Nurse Teacher Scale (CLES+T).
AB  - BACKGROUND AND PURPOSE: The Clinical Learning Environment, Supervision and Nurse
      Teacher (CLES+T) scale measures student nurses' perceptions of clinical learning
      environments. This study evaluates the construct validity and internal
      reliability of the CLES+T in hospital settings in New Zealand. Comparisons are
      made between New Zealand and Finnish data. METHODS: The CLES+T scale was
      completed by 416 Bachelor of Nursing students following hospital clinical
      placements between October 2008 and December 2009. Construct validity and
      internal reliability were assessed using exploratory factor analysis and
      Cronbach's alpha. RESULTS: Exploratory factor analysis supports 4 factors.
      Cronbach's alpha ranged from .82 to .93. All items except 1 loaded on the same
      factors found in unpublished Finnish data. The first factor combined 2 previous
      components from the published Finnish component analysis and was renamed:
      connecting with, and learning in, communities of clinical practice. The remaining
      3 factors (Nurse teacher, Supervisory relationship, and Leadership style of the
      manager) corresponded to previous components and their conceptualizations.
      CONCLUSION: The CLES+T has good internal reliability and a consistent factor
      structure across samples. The consistency across international samples supports
      faculties and hospitals using the CLES+T to benchmark the quality of clinical
      learning environments provided to students.

PMID- 24851672
TI  - Sensing parts-per-trillion Cd(2+), Hg(2+), and Pb(2+) collectively and
      individually using phosphorothioate DNAzymes.
AB  - Cadmium, mercury, and lead are collectively banned by many countries and regions
      in electronic devices due to their extremely high toxicity. To date, no sensing
      method can detect them as a group and also individually with sufficient
      sensitivity and selectivity. An RNA-cleaving DNAzyme (Ce13d) was recently
      reported to be active with trivalent lanthanides, which are hard Lewis acids. In
      this work, phosphorothioate (PS) modifications were systematically made on Ce13d.
      A single PS modification at the substrate cleavage site shifts the activity from
      being dependent on lanthanides to soft thiophilic metals. By incorporating the PS
      modification to another DNAzyme, a sensor array was prepared to detect each
      metal. Individual sensors have excellent sensitivity (limit of detection = 4.8 nM
      Cd(2+), 2.0 nM Hg(2+), and 0.1 nM Pb(2+)). This study provides a new route to
      obtain metal-specific DNAzymes by atomic replacement and also offers important
      mechanistic insights into metal binding and DNAzyme catalysis. 

PMID- 24851673
TI  - Fragment quantum mechanical calculation of proteins and its applications.
AB  - Conspectus The desire to study molecular systems that are much larger than what
      the current state-of-the-art ab initio or density functional theory methods could
      handle has naturally led to the development of novel approximate methods,
      including semiempirical approaches, reduced-scaling methods, and fragmentation
      methods. The major computational limitation of ab initio methods is the scaling
      problem, because the cost of ab initio calculation scales nth power or worse with
      system size. In the past decade, the fragmentation approach based on chemical
      locality has opened a new door for developing linear-scaling quantum mechanical
      (QM) methods for large systems and for applications to large molecular systems
      such as biomolecules. The fragmentation approach is highly attractive from a
      computational standpoint. First, the ab initio calculation of individual
      fragments can be conducted almost independently, which makes it suitable for
      massively parallel computations. Second, the electron properties, such as density
      and energy, are typically combined in a linear fashion to reproduce those for the
      entire molecular system, which makes the overall computation scale linearly with
      the size of the system. In this Account, two fragmentation methods and their
      applications to macromolecules are described. They are the electrostatically
      embedded generalized molecular fractionation with conjugate caps (EE-GMFCC)
      method and the automated fragmentation quantum mechanics/molecular mechanics (AF
      QM/MM) approach. The EE-GMFCC method is developed from the MFCC approach, which
      was initially used to obtain accurate protein-ligand QM interaction energies. The
      main idea of the MFCC approach is that a pair of conjugate caps (concaps) is
      inserted at the location where the subsystem is divided by cutting the chemical
      bond. In addition, the pair of concaps is fused to form molecular species such
      that the overcounted effect from added concaps can be properly removed. By
      introducing the electrostatic embedding field in each fragment calculation and
      two-body interaction energy correction on top of the MFCC approach, the EE-GMFCC
      method is capable of accurately reproducing the QM molecular properties (such as
      the dipole moment, electron density, and electrostatic potential), the total
      energy, and the electrostatic solvation energy from full system calculations for
      proteins. On the other hand, the AF-QM/MM method was used for the efficient QM
      calculation of protein nuclear magnetic resonance (NMR) parameters, including the
      chemical shift, chemical shift anisotropy tensor, and spin-spin coupling
      constant. In the AF-QM/MM approach, each amino acid and all the residues in its
      vicinity are automatically assigned as the QM region through a distance cutoff
      for each residue-centric QM/MM calculation. Local chemical properties of the
      central residue can be obtained from individual QM/MM calculations. The AF-QM/MM
      approach precisely reproduces the NMR chemical shifts of proteins in the gas
      phase from full system QM calculations. Furthermore, via the incorporation of
      implicit and explicit solvent models, the protein NMR chemical shifts calculated
      by the AF-QM/MM method are in excellent agreement with experimental values. The
      applications of the AF-QM/MM method may also be extended to more general
      biological systems such as DNA/RNA and protein-ligand complexes. 

PMID- 24851674
TI  - When 'sperm' becomes 'donor': transitions in parents' views of the sperm donor.
AB  - Abstract Little is known about recipients' views of their sperm donor. This study
      aimed to examine the possible transitions or consistencies in donor sperm
      recipients' (DSRs') view on the sperm donor over time. A longitudinal qualitative
      study of 19 Belgian heterosexual DSRs was undertaken. Interviews took place with
      both partners of the couple during pregnancy, at birth and 1.5-2 years after
      birth, and were analysed using a grounded theory approach. Recipients who
      intended to disclose exhibited a transition in their awareness of the donor from
      being of minimal importance to one who was increasingly seen as part of their
      family narrative. This was partly triggered by the offspring's life, remarks
      about resemblance and the socio-cultural context. The perceived position of the
      donor changed for most recipients from a threatening rival to a 'distractor'.
      This change was supported by the emerging father-child bond and the confidence
      that stemmed from it. These observations were applicable to those recipients who
      intended to disclose their donor conception; for those recipients who intended
      not to disclose, little or no transition was observed. This study describes and
      analyses the transitions and consistencies in recipients' views of the donor over
      different stages of the family life-cycle (pregnancy, birth, toddler stage) and
      could help the fertility clinics tailor their counselling to the specific stages
      of parenthood. 

PMID- 24851675
TI  - Heterotriangulenes pi-expanded at bridging positions.
AB  - A series of nitrogen-containing heterotriangulenes expanded at the bridging
      positions has been synthesized. Among them, a dibenzo[c,g]fluorenylidene
      substituted derivative has a highly twisted conformation for the overcrowded
      alkene moieties, which impart a highly electron-accepting character to the
      electron-donating heterotriangulene skeleton and thereby an NIR absorption as
      well as multiredox properties with a low reduction potential. 

PMID- 24851677
TI  - [The ultimate goals of treatment in systemic lupus erythematosus are long-term
      preservation of organ function, and improved quality of life and survival].

PMID- 24851676
TI  - Gambling in Brazil: a call for an open debate.
AB  - AIMS: To provide an overview of gambling in Brazil, including historical
      background, past and current legislation, gamblers' profile, treatment and
      research initiatives. METHODS: Review of the published literature and research
      reports. RESULTS: Gambling is deeply rooted in Brazilian history and culture, but
      gambling regulation historically alternates between legalization and banning.
      Currently, only state lotteries, horse betting and poker-playing are allowed.
      There is pressure to widen the games repertoire, but efforts at full legalization
      and commercial exploration of gambling have receded. Despite the barriers to
      gambling access, Brazil has prevalence rates similar to other countries: 1.0 and
      1.3% life-time prevalence for pathological and problem gambling. A faster
      progression from regular to problem gambling was found among middle-aged women in
      clinical samples and for adolescent male gamblers in a population-based sample.
      Youth gambling is associated with severe forms of gambling and other risk-taking
      behaviours. Treatment options are scarce, and the public health system is
      unprepared to support gambling patients. Ongoing incipient efforts are being made
      to establish a treatment model combining psychotherapy and psychiatric
      comorbidity treatment with promotion of quality of life. CONCLUSION: Life-time
      incidence of pathological gambling in Brazil appears similar to many other
      countries, at approximately 1%. Arguably, there is a need to develop a more
      coherent regulatory and treatment response to this societal problem.

PMID- 24851678
TI  - [The era of reduced glucocorticoid treatment in lupus is coming].

PMID- 24851679
TI  - [Long-term effects of hydroxychloroquine on metabolism of serum lipids and left
      ventricular structure and function in patients of systemic lupus erythematosus].
AB  - OBJECTIVE: To observe the long-term effects of hydroxychloroquine treatment on
      blood lipids and left ventricular function of systemic lupus erythematosus (SLE)
      patients. METHODS: A total of 72 SLE patients were randomly divided into 2 groups
      of hydroxychloroquine treatment (n = 36) and non-hydroxychloroquine (n = 36). The
      serum level of lipids, left ventricular end-diastolic diameter (LVEDD), left
      ventricular end-systolic diameter (LVESD), interventricular septum thickness
      (IVST), left ventricular posterior wall thickness (LVPWT), fractional shortening
      rate (FS), left ventricular ejection fraction (LVEF) and E/A ratio were measured
      before, 6 month, 12 month and 2 years after treatment. RESULTS: After long-term
      use of hydroxychloroquine, there were statistically differences in the levels of
      total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL) and high
      density lipoprotein (HDL). And LVEDD, LVWPT and E/A were statistically different
      (P < 0.05) before and after hydroxychloroquine dosing. CONCLUSION: The long-term
      use of hydroxychloroquine may improve lipid metabolism and left ventricular
      function in SLE patients.

PMID- 24851680
TI  - [Systemic lupus erythematosus associated pulmonary arterial hypertension:
      clinical analysis of 91 cases].
AB  - OBJECTIVE: To explore the clinical characteristics and therapeutic efficacy of
      systemic lupus erythematosus (SLE) associated pulmonary arterial hypertension
      (PAH). METHODS: A total of 91 cases of SLE-PAH from 2007 to 2011 were reviewed
      and followed up. They were divided into 2 groups: group A: New York Heart
      Association (NYHA) functional class 1 and 2; group B: NYHA functional class 3 and
      4. RESULTS: There were 2 males and 89 females with a mean age of 37 +/- 11 years.
      The mean duration of SLE disease process was 7 +/- 6 years. PAH was the primary
      symptom of SLE onset in 10 cases. Pulmonary arterial systolic pressure (PASP) as
      measured by ultrasonic cardiography (UCG) were between 40 to 128 mmHg. Eighteen
      cases (19.78%) underwent right heart catheterization (RHC). There were good
      parallels of PASP value between RHC and UCG. The main characteristics included
      Raynaud's phenomenon (53.8%), pericardial effusion (51.6%) and a high titer of
      anti-RNP antibody (57.1%). PASP was positively associated with SLE disease
      activity in mild and moderate cases. Among 27 mortality cases, there were 4 in
      group A (14.8%) and 23 in group B (85.2%) . And the causes of immortality were
      mostly non-cardiac in group A and right heart failure in group B.
      Cyclophosphamide was effective in mild and moderate cases. Forty-four cases
      received PAH target treatment and it could decrease the PASP in mild and moderate
      cases and significantly prolong the survival for severe cases. CONCLUSION: The
      major clinical characteristics of SLE-PAH patients include Raynaud's phenomenon,
      pericardial effusion and positivity of anti-RNP antibody. PASP is positively
      associated with SLE disease activity in mild and moderate cases for whom
      intravenous pulse cyclophosphamide therapy may be effective. For severe cases,
      concomitant PAH target therapy may significantly improve the prognosis.

PMID- 24851681
TI  - [Clinical features and prognosis of patients with lupus nephritis].
AB  - OBJECTIVE: To explore the clinical features and prognosis of patients with lupus
      nephritis (LN) in a large multicenter lupus cohort of Jiangsu Province. METHODS:
      Medical records of 2 078 systemic lupus erythematosus (SLE) inpatients from 15
      hospitals at the first admission from 1999 to 2012 were reviewed and classified
      into two groups with LN or without. The clinical features between two groups were
      compared with Mann-Whitney U or Chi-square test and potentially associated
      factors tested by Cox regression. RESULTS: A total of 883 (42.5%) hospitalized
      lupus patients were diagnosed as LN. And the median age at disease onset of LN
      patients was lower than that of those without LN [(30 +/- 11) vs (32 +/- 12)
      years, P < 0.01]. Cardiopulmonary involvement, neuropsychiatric disorder,
      gastrointestinal dysfunction, hematologic disease, ophthalmopathy, SLEDAI score >
      9 at admission and SLE disease activity index (SLEDAI) score > 9 at discharge
      were more often seen in patients with LN compared to those without LN (31.5%,
      7.9%, 13.9%, 69.0%, 1.5%, 77.4%, 29.8% vs 18.8%, 5.1%, 6.8%, 63.1%, 0.3%, 43.1%,
      8.1%, all P < 0.01). The mortality rates at 1 or 5 years after first admission
      were both significantly higher in LN patients than those without LN (7.2%, 15.0%
      vs 3.1%, 6.3%, P < 0.01). Independent predictors for mortality in patients with
      LN were neuropsychiatric involvement[hazard ratio (HR) 2.46], SLEDAI score > 9 at
      discharge (HR 2.34), increased serum creatinine (HR 2.21) and elevated alanine
      aminotransferase and (or) aspartate transaminase (HR 2.09) whereas
      glucocorticosteroid therapy (HR 0.18) was a protective factor. CONCLUSION: LN is
      one common complication of SLE patients during an early stage. And LN patients
      are more prone to present other vital organ involvement, higher disease activity
      and worse treatment outcomes. When accompanied with neuropsychiatric involvement,
      increased serum creatinine or elevated transaminase, worse prognosis is expected.
      Glucocorticosteroid treatment may offer some benefits.

PMID- 24851682
TI  - [Assessment of ovarian reserve with anti-Mullerian hormone in female patients
      with systemic lupus erythematosus].
AB  - OBJECTIVE: To evaluate the serum level of anti-Mullerian hormone (AMH) in female
      patients with systemic lupus erythematosus (SLE) and identify its correlations
      with age and cyclophosphamide (CYC) therapy. METHODS: A total of 77 SLE female
      patients and 38 control healthy women with regular menstrual cycles were
      recruited. AMH was measured by enzyme linked immunosorbent assay (ELISA) kit.
      Follicle-stimulating hormone (FSH), estradiol (E2) and antral follicle count
      (AFC) of bilateral ovary were detected at the third day of menstrual cycle.
      RESULTS: Their mean age was (29 +/- 5) years (range, 20-40) and the mean duration
      (2.7 +/- 2.4) years. The mean serum level of AMH was (1.5 +/- 1.3) ug/L and AFC
      10 +/- 7. Linear regression revealed AFC (r = 0.9, P < 0.01) was associated with
      the level of AMH. The mean levels of AMH and AFC were significantly higher in
      patients naive to CYC therapy than in those under exposure, but lower than that
      in healthy control (P < 0.01). No difference existed in FSH and E2 among 3
      groups. Compared with those above 30 years old, the patients aged 30 years and
      younger had significantly higher level of AMH (P < 0.01). The Spearman's
      correlation analysis indicated that each 5 gm of CYC exposure were independently
      associated with a lower level of AMH (r = -0.4, P < 0.01). CONCLUSION: As a more
      sensitive marker of ovarian reserve, AMH is associated with age and the
      cumulative dose of CYC. SLE patients aged >30 years and under exposure to CYC >10
      g should be closely monitored for potential adverse events.

PMID- 24851683
TI  - [Prospective study of efficacy and safety of hydroxychloroquine in pregnant
      patients with systemic lupus erythematosus].
AB  - OBJECTIVE: To evaluate the efficacy and safety of hydroxychloroquine (HCQ) in
      pregnant patients with systemic lupus erythematosus (SLE). METHODS: A total of 48
      pregnant patients with SLE were prospectively recruited from January 2010 to
      December 2012 at Peking Union Medical College Hospital. Diseases were stable,
      functions of important organs normal and immunosuppressants were discontinued for
      at least 6 months. Prednisone ( <= 15 mg qd ) and HCQ (0.2 bid) were taken during
      the whole pregnancy. SLE disease activity before, during and after pregnancy and
      pregnancy outcome were analyzed. RESULTS: SLE relapsed in 9(18.8%) patients
      during pregnancy and 2 (4.2%) cases relapsed after delivery. There was no
      mortality. And 44 cases (91.7%) had successful pregnancy with 12 (27.3%) preterm
      infants and 13 (29.6%) infants with low birth weight. All neonates grew
      healthily, except one with hypoevolutism because of premature growth . Neither
      visual field nor fundus showed any abnormality. CONCLUSION: HCQ may be effective
      in improving the pregnancy and fetal outcomes in SLE patients. And it is safe for
      pregnant women and fetuses. The patients should be regularly monitored and
      followed up.

PMID- 24851684
TI  - [Characteristics of cognitive impairment in adults with cerebral ischemia].
AB  - OBJECTIVE: To explore the characteristics of cognitive impairment of cerebral
      ischemia in adults to provide rationales for proper diagnosis and targeted
      treatment. METHODS: A battery of standardized neuropsychological tests including
      mini-mental state examination (MMSE) and memory and executive screening (MES) was
      administered in a cohort of consecutive patients with cerebral ischemia.
      According to the screening results, they were divided into 3 subgroups of
      vascular dementia (VaD), vascular mild cognitive impairment (VaMCI) and non
      vascular cognitive impairment (VCI). The general profiles of 3 subgroups were
      compared and the characteristics of VaMCI subgroup examined. Then the
      relationship between the composition of cognitive impairment and the type of
      ischemia (stroke and transient ischemic attack) was analyzed. RESULTS: Fifty-six
      patients and 48 healthy subjects (normal control group) matched with regards to
      age, gender and education were recruited. Compared to normal control group, there
      was a decline in the scores of MMSE [(25.0 +/- 5.6) vs (28.0 +/- 1.4); t = 2.695,
      P = 0.007] and MES [(67 +/- 21) vs (84 +/- 7); z = 3.860, P = 0.000] in case
      group. There were 33 cases (58.9%) of VCI in case group, including 11 (19.6%) in
      VaD subgroup, 22 (39.3%) in VaMCI subgroup and 23 (41.1%) in non-VCI subgroup.
      And the rate of VaD/VaMCI was 1/2. The percentage of males (36.4% vs 78.3%;
      chi(2) = 5.720, P = 0.017) and education [(8 +/- 3) vs (12 +/- 4); P = 0.010] of
      VaD subgroup were significantly lower than that of non-VCI subgroup; the
      education of VaMCI subgroup was significantly lower than that of non-VCI subgroup
      [(7 +/- 3) vs (12 +/- 4); P = 0.001]; a positive correlation existed between
      scores of MMSE/MES and cognitive impairment. The neuropsychological tests were
      both sensitive and specific.In VaMCI subgroup, 22 cases (100%) presented with a
      deficit of at least 1 certain executive function/attention index, 21(95.5%) with
      at least 1 certain memory index, 17(77.3%) with at least 1 certain language index
      and 16(72.7%) with at least 1 certain visuospatial function index; all VaMCI
      cases presented with comprehensive cognitive impairment: 11 (50%) in 4 domains,
      10 (45%) in 3 domains and 1 (5%) in 2 domains.No significant difference existed
      among 3 subgroups with regard to type of ischemia (chi(2) = 1.111, P = 0.574). In
      the case group, 30 patients suffered stroke and 17 (56.7%) had an onset of VCI
      with a rate of VaMCI/VCI at 58.8%; transient ischemic attack occurred in 26
      patients and 16 (61.5%) suffered VCI with a rate of VaMCI/VCI at 75.0%.
      CONCLUSION: Our study not only profiles the prevalence and peculiarity of
      cognitive impairment in patients with cerebral ischemia, but also provides
      concrete rationales for further diagnosis and classification of VCI.

PMID- 24851685
TI  - [Correlation between serum levels of homocysteine and folate and cognitive
      dysfunction in first-episode schizophrenics].
AB  - OBJECTIVE: To explore the correlation between serum levels of homocysteine (Hcy)
      and folate and cognitive function in first-episode drug-naive schizophrenics.
      METHODS: A total of 60 first-episode schizophrenics (schizophrenia group) from
      our hospital and 60 healthy individuals (control group) were enrolled.Serum
      levels of folate and Hcy were measured with electrochemical luminescence method
      and enzymatic cycling assay respectively. Positive and Negative Syndrome Scale
      (PANSS) was used to evaluate the mental symptoms and Matrics Consensus Cognitive
      Battery (MCCB) was used to evaluate the cognitive function. RESULTS: Serum level
      of folate in schizophrenia group (4.1 +/- 1.9 ng/ml) was lower than that in
      control group (7.5 +/- 1.9 ng/ml) (P < 0.001). And serum level of Hcy in
      schizophrenia group (27 +/- 9 umol/L) was significantly higher than that in
      control group (18 +/- 6 umol/L) (P = 0.006). Serum level of folate in
      schizophrenia group had negative correlations with Hcy level (r = -0.38, P =
      0.002) and negative symptoms (r = -0.25, P < 0.05) while Hcy level was negatively
      correlated with cognitive function scores (r = -0.38, r = -0.33, r = -0.30, r = 
      0.30, P < 0.05). CONCLUSION: Serum level of folate decreases while serum level of
      Hcy increases in first-episode schizophrenics. Both have some relevance with
      mental symptom and cognitive dysfunction.

PMID- 24851686
TI  - [Prognostic outcomes of adherence to guideline of bundle therapy by key points of
      control strategies in septic shock patients].
AB  - OBJECTIVE: To evaluate the improvement of clinical septic shock guideline of
      bundle therapy by key points of control strategies and its impact on the outcomes
      of septic shock patients. METHODS: The quality control team and sepsis steering
      committee were established to apply key points of control strategies to improve
      the clinical septic shock guideline of bundle therapy. The time to resuscitation,
      antibiotics and cultures, the implementation rate of 6-hour resuscitation goals,
      glucose control and lung protective ventilation strategies were recorded during
      the plan-do-check-act (PDCA) steps. And the changes of length of ICU stay and
      hospital mortality were analyzed. RESULTS: Between July 2009 and December 2012, a
      total of 563 sequential septic shock patients were admitted. Demographics
      included median age, gender ratio, initial Acute Physiology and Chronic Health
      Evaluation II (Apache II) score and sources of infection showed no significant
      differences during this period. Compared with 2009, the time to resuscitation
      (65.1 +/- 10.3 vs 99.7 +/- 10.5 min, P < 0.01) , the time to cultures (55.9 +/-
      5.2 vs 71.5 +/- 7.9 min, P < 0.01) and the time to antibiotics (58.1 +/- 5.8 vs
      152.8 +/- 16.1 min, P < 0.01) significantly decreased in 2012. The implementation
      rate of 6-hour resuscitation goals (68.7% vs 28.7%, P < 0.01) , the
      implementation rate of glucose control (79.6% vs 40.0%, P < 0.01) and the
      implementation rate of lung protective ventilation strategies (74.1% vs 51.4%, P
      = 0.004) improved significantly form 2009 to 2012. The length of ICU stay (7.2 +/
      1.5 vs 9.8 +/- 2.7 d, P < 0.01) decreased. And hospital mortality decreased from
      40.0% in 2009 to 23.1% in 2012 (P = 0.015). CONCLUSION: The key points of control
      strategies can improve the clinical septic shock guideline of bundle therapy
      performance so that there are significant decreases of length of ICU stay and
      hospital mortality of septic shock patients.

PMID- 24851687
TI  - [Strengthened respiratory management for lower tracheostomy risks in patients
      with complete cervical spinal cord injury].
AB  - OBJECTIVE: To access the feasibility of reducing tracheostomy rates in patients
      with complete cervical spinal cord injury through a systemic respiratory
      management mode. METHODS: A retrospective review was performed for 239 patients
      on a systemic respiratory management mode after complete cervical spinal cord
      injury in Shanghai Changzheng Hospital from 2006 to 2012. Their demographic and
      clinical data, including age, gender, cause of injury, level of cervical spinal
      cord injuries, surgical approaches, tracheostomy rates and mortality rates, were
      collected and analyzed. Tracheostomy rates were compared with those of patients
      with complete cervical spinal cord injury. Tracheostomy rates were compared with
      those patients with complete cervical spinal cord injury from 1991 to 2005. The
      new respiratory management mode for patients with severe cervical spinal cord
      injury included maintaining adequate energy and water for patients, relieving
      bronchospasm, loosening phlegm, strengthening body-turning and backslapping,
      sputum aspiration with suction tube through nasal cavity or bronchofibroscope,
      strengthening deep breath and cough training, strict control of tracheostomy
      indications and short-term postoperative intubation reserving if necessary.
      RESULTS: 32 patients were implemented tracheostomy. The tracheostomy rate was
      13.4%. 10 patients died, the mortality rate was 4.18%. However, the tracheostomy
      rate was 19.1% and mortality rate 21.4% from 1991 to 2005. The tracheostomy rate
      was significantly lower than before and survival rate improved significantly.
      CONCLUSION: The systemic respiratory management mode can effectively reduce
      tracheostomy rate of patients with complete cervical spinal cord injury and
      improve their survival rate.

PMID- 24851688
TI  - [Efficacy and prognostic factors of preoperative radiation therapy of elbow
      arthrolysis].
AB  - OBJECTIVE: To assess the efficacy and prognostic factors of preoperative
      radiation therapy in patients of elbow arthrolysis. METHODS: From October 2008 to
      September 2010, 43 patients with heterotopic ossification (HO) history at elbow
      were studied retrospectively. Radiation therapy was given in single fraction of 8
      Gy within 1-4 h pre-operation. The elbow HO classifications at preoperation and
      the last follow-up were analyzed and their efficacy and related prognostic
      factors evaluated. RESULTS: The median follow-up period was 34 (23.24-46.26)
      months. The elbow function of 19 (44.2%) cases returned to normal. One case was
      ineffective. Only one case had vulnus swelling. Graham and Hastings HO
      classification scores were significantly different between pre-operation and the
      last follow-up (Z = -5.899, P = 0.000). Logistic analysis showed that age and
      time between diagnoses and treatment had a significant influence of elbow HO.
      CONCLUSION: Preoperative radiation therapy of 8 Gy within 1-4 h of elbow
      arthrolysis is both safe and effective. And greater age, milder wound and longer
      time between diagnoses and treatment have better outcomes.

PMID- 24851689
TI  - [Effects of volume-controlled ventilation and pressure-controlled volume-
      guaranteed mode during one-lung ventilation on circulation, pulmonary function
      and lung injury].
AB  - OBJECTIVE: To compare the effects of volume-controlled ventilation (VCV) and
      pressure-controlled volume-guaranteed (PCV-VG) mode during one-lung ventilation
      (OLV) on circulation, pulmonary function and lung injury. METHODS: 2012 February
      to 2013 March in Ningbo No2. Hospital cardiothoracic surgery, 30 patients aged 52
      to 76 years (ASA grade II-III) undergoing elective thoracoscopic lobectomy were
      randomly divided into VCV group and PCV-VG group, with 15 cases in each group.
      After anesthesia induction and endotracheal intubation, endobronchial blocker was
      inserted to start OLV. Heart rate (HR), mean arterial pressure (MAP), measured
      tidal volume (TV), peak airway pressure (Ppeak), airway resistance (Raw), chest
      compliance (Cdyn) and the end-tidal carbon dioxide pressure (PetCO(2)) were
      recorded at the time point of 15 minutes after turning to the lateral position,
      15 minutes and 60 minutes after OLV, and 15 minutes after the resumption of two
      lung ventilation. In the meanwhile, arterial blood gas analysis was conducted to
      measure indicators of pH, oxygen tension (PaO(2)) and carbon dioxide partial
      pressure (PaCO(2)). Blood was drawn before induction, 1 hour after OLV and 1 hour
      after the end of surgery, and the concentration of interleukin-6 (IL-6) and tumor
      necrosis factor-alpha (TNF-alpha) were detected by enzyme-linked immunosorbent
      assay (ELISA). RESULTS: HR, MAP, TV, PetCO(2), pH and PaCO(2) in two groups at
      the time point of 15 minutes after turning to the lateral position, 15 minutes
      and 60 minutes after OLV, and 15 minutes after the resumption of two lung
      ventilation showed no significant difference (P > 0.05). At the point of 15
      minutes after turning to the lateral position and 15 minutes after two lung
      ventilation, Ppeak and Cdyn of two groups were significantly different (P < 0.05)
      (Ppeak:16 +/- 3 cmH(2)O, 16 +/- 3 cmH(2)O for VCV group and 14 +/- 2 cmH(2)O, 14
      +/- 2 cmH(2)O for PCV-VG group; Cdyn: 43.5 +/- 5.9 ml/cmH(2)O, 43.8 +/- 6.7
      ml/cmH2O for VCV group and 49.7 +/- 7.1 ml/cmH(2)O, 53.3 +/- 9.6 ml/cmH(2)O for
      PCV-VG group). Compared with VCV group, PCV-VG group showed a lower Ppeak 15
      minutes and 60 minutes after OLV [ (17 +/- 2 cmH(2)O) vs (22 +/- 4 cmH(2)O) and
      (18 +/- 4 cmH(2)O) vs( 23 +/- 3 cmH(2)O) with a higher Cdyn at the same point
      (38.6 +/- 6.3 ml/cmH(2)O) vs (29.6 +/- 3.2 ml/cmH(2)O) and 37.3 +/- 6.0
      ml/cmH(2)O) vs (30.3 +/- 3.8 ml/cmH(2)O)] (P < 0.01). Compared with VCV group,IL
      6 and TNF-alpha of PCV-VG group 1 hour after OLV and 1 hour after the end of
      surgery were significantly lower (P < 0.01) (IL-6: 52.32 +/- 3.59 vs 62.65 +/-
      4.17 pg/ml and 63.57 +/- 4.98 vs 82.38 +/- 4.10 pg/ml; TNF-alpha: 3.23 +/- 0.27
      vs 4.19 +/- 0.38 pg/ml and 4.01 +/- 0.28 vs. 5.49 +/- 0.31 pg/ml). CONCLUSION:
      During one-lung ventilation in thoracoscopic lobectomy, PCV-VG mode has a
      competitive advantage over VCV mode in terms of pulmonary function and lung
      protection.

PMID- 24851690
TI  - [Diagnostic value of solid component for lung adenocarcinoma shown as ground
      glass nodule on computed tomography].
AB  - OBJECTIVE: To explore the feasibility of making a preoperative diagnosis of lung
      adenocarcinoma shown as ground-glass nodule (GGN) on computed tomography (CT).
      METHODS: A total of 143 GGN lesions proved pathologically were divided randomly
      into A and B groups. Then each group was further divided pathologically into
      preinvasive lesion, minimal invasive adenocarcinoma (MIA) and invasive
      adenocarcinoma (IAC) subgroups. Group A (n = 101), size of lesion, proportion of
      ground glass opacity (GGO) composition of lesion, long diameter, longest diameter
      and size of solid component in lesion were measured on CT so as to establish the
      CT diagnostic standard of lung adenocarcinoma shown as GGN on CT. Group B (n =
      42) was employed to evaluate the accuracy of the above CT diagnostic standard.
      SPSS 17.0 software was used for statistical analysis. RESULTS: Significant
      statistic significance existed in all parameters among all groups (P < 0.05). All
      parameters were correlated the pathologic type of lesion. The differences were
      statistically significant (P = 0.000). Through the receiver operating
      characteristic (ROC) curve, between groups of preinvasive lesion and MIA, each
      parameter had a medium diagnostic value of 0.70-0.90; between groups of MIA and
      IAC, size of lesion and long diameter of solid component in lesion had a medium
      diagnostic value of 0.70-0.90, longest diameter of solid component, size of solid
      component in lesion and proportion of GGO composition of lesion had a high
      diagnostic value with an AUC of >0.90. The CT diagnostic standard, derived from
      group A, was used to analyze the pathologic type of group B. And t no significant
      statistic significance existed between CT preoperative diagnosis and operative
      pathologic diagnosis (P > 0.05) . The correct diagnosis rates of size of lesion,
      proportion of GGO composition of lesion, long diameter, longest diameter and size
      of solid component in lesion were 71.43%, 76.19%, 90.05%, 90.05% and 88.10%
      respectively. CONCLUSION: Based upon size of lesion, proportion of GGO
      composition of lesion, long diameter, longest diameter and size of solid
      component in lesion, preoperative CT examination may be used to determine the
      pathological types of lung adenocarcinoma shown as GGN.

PMID- 24851691
TI  - [Study of ADC value in healthy adults kidney of different age groups].
AB  - OBJECTIVE: To evaluate the changes of ADC value on renal parenchyma at different
      age groups in healthy adults. METHODS: One hundred healthy adults were divided
      into five groups based on age:namely 18-29 years, 30-39 years, 40-49 years, 50-59
      years and 60-69 years. All adults underwent diffusion-weighted magnetic
      resonance(MR) imaging of the kidneys with b values of 800 s/mm(2). ADC values of
      renal parenchyma were measured by the manufacturer's software. RESULTS: With the
      increasing of age , the renal parenchyma ADCs decrease. The ADCs of renal
      parenchyma in five age groups were (2.07 +/- 0.10) *10(-3)mm(2)/s, (2.06 +/-
      0.12) *10(-3)mm(2)/s, (2.03 +/- 0.10) *10(-3)mm(2)/s, (1.98 +/- 0.17) *10(
      3)mm(2)/s and (1.94 +/- 0.12) *10(-3)mm(2)/s, which had statistically significant
      different (F = 3.375, P < 0.05). CONCLUSION: (1)The ADCs of renal parenchyma may
      be influenced by age , with the increasing of age, ADCs of normal kidney
      presented tenuous decreasing tendency especially the people aged >= 40 years;
      (2)in clinical application, we ought to pay attention to the influence of age
      factor. Income data of this study can be took as normal reference value in other
      more study.

PMID- 24851692
TI  - [Efficacy of short-term catheter-directed thrombolysis used with rt-PA combined
      with endovascular interventional therapy in patients with lower limb ischemia].
AB  - OBJECTIVES: To evaluate the performance effect of short-term catheter-directed
      thrombolysis with different dosage of rt-PA allied with endovascular
      interventional therapy for patients with acute lower limb ischemia. METHODS: To
      separate 84 consecutive patients suffered from acute lower limb ischemia into two
      groups at random, then adopt catheter-directed thrombolysis for each group of
      patients injected 20 mg (Group A) or 10 mg (Group B) rt-PA into the occlusive
      lesion correspondingly, and subsequently perform endovascular intervention on
      significant underlying lesions on the base of angiography results. Adopt
      statistical methods to assess treatment effectiveness, rates of complication and
      amputation rates within 30 days, 6 months or 12 months. The statistic analysis
      was performed under SPSS 16.0 format, and adopts t test and chi(2) test. RESULTS:
      There was no statistical difference on patient characteristics and lesions
      between both groups (P > 0.05). Procedural success rates as well clinical success
      rates were all 100%. Not incur any diversity on thrombolysis effectiveness
      between both groups injected different dosage of rt-PA (P > 0.05). Not found
      major differences on ratios of PTA or implant stent between both groups (P >
      0.05). During the follow-up period of 30-day, 6-, 12- months, there were no
      statistical differences on the amputation-free survival rates and complication
      rates between both groups. CONCLUSIONS: Whereas short-term catheter-directed
      thrombolysis combined with endovascular interventional therapy won good operation
      effectiveness on patients with acute lower limb ischemia, moreover the dosage of
      rt-PA did not impact on thrombolysis, it is worthy to be applied in the clinical
      practice.

PMID- 24851693
TI  - [Multifunctional nano-vector for gene delivery into human adipose derived
      mesenchymal stem cells and in vitro cellular magnetic resonance imaging].
AB  - OBJECTIVE: To examine the feasibility and efficacy of using superparamagnetic
      iron oxide nanoparticles coated with polyethylene glycol-grafted polyethylenimine
      (PEG-g-PEI-SPION) as a carrier for gene delivery into human adipose derived
      mesenchymal stem cells (hADMSCs) and in vitro cellular magnetic resonance imaging
      (MRI). METHODS: PEG-g-PEI-SPION was synthesized as previously reported. Gel
      electrophoresis was performed to assess the pDNA condensation capacity of PEG-g
      PEI-SPION. The particle size and zeta potential of PEG-g-PEI-SPION/pDNA complexes
      were determined by dynamic light scattering. Cytotoxicity of PEG-g-PEI-SPION was
      evaluated by CCK-8 assay with hADMSCs. Gene transfection efficiency of PEG-g-PEI
      SPION in hADMSCs was quantified by flow cytometry. The cellular internalization
      of PEG-g-PEI-SPION/pDNA nanocomplexes was studied by confocal laser scanning
      microscopy and Prussian blue staining. MRI function of PEG-g-PEI-SPION was
      studied by in vitro cellular MRI scanning. RESULTS: PEG-g-PEI-SPION condensed
      pDNA to form stable complexes of 80-100 nm in diameter and showed low
      cytotoxicity in hADMSCs. At the optimal N/P ratio of 20, PEG-g-PEI-SPION/pDNA
      obtained the highest transfection efficiency of 22.8% +/- 3.6% in hADMSCs. And it
      was higher than that obtained with lipofectamine 11.2% +/- 2.6% (P < 0.05).
      Furthermore, hADMSCs labeled with PEG-g-PEI-SPION showed sensitive low signal
      intensity on MRI T2-weighted images in vitro. CONCLUSION: PEG-g-PEI-SPION is an
      efficient and MRI-visible nano-vector for gene delivery into hADMSCs.

PMID- 24851694
TI  - [Notch signaling pathway in 1-methyl-4-phenylpyridinium-induced apoptosis of SH
      SY5Y cell].
AB  - OBJECTIVE: To explore the role of Notch signaling pathway and the effect of gamma
      secretase inhibitor (DAPT) on the apoptosis induced by 1-methyl-4
      phenylpyridinium (MPP(+)) in differentiated SH-SY5Y cell. METHODS: SH-SY5Y cell
      were incubated with various concentrations (0, 0.5, 1, 1.5, 2 mmol/L) of MPP(+)
      for 0, 24, 48 and 72 h respectively. Flow cytometry with Annexin V-FITC/PI double
      staining was used for apoptotic analysis. The protein expressions of Notch-1,
      Jagged-1 and Hes-1 were detected by Western blot. SH-SY5Y cell were preincubated
      with 10 umol/L DAPT for 15 min before 1.5 mmol/L MPP(+) treatment for 48 h. Flow
      cytometry and Western blot were performed to analyze the cell apoptosis and
      protein expressions of Notch-1, Jagged-1 and Hes-1. RESULTS: MPP(+) induced the
      apoptosis of SH-SY5Y cell in a dose (3.20% +/- 0.19% vs 10.00% +/- 1.72%, 20.60%
      +/- 3.76%, 32.80% +/- 5.12%, 46.00% +/- 5.06%, all P < 0.05) and time- (2.80% +/-
      0.21% vs 12.30% +/- 1.82%, 19.60% +/- 2.89%, 35.00% +/- 4.78%, all P < 0.05)
      dependent manner. MPP(+) up-regulated the expressions of Notch-1, Jagged-1 and
      Hes-1 in a dose- and time-dependent manner in SH-SY5Y cell. DAPT treatment
      decreased MPP(+)-induced apoptosis (3.10% +/- 0.21% vs 35.50% +/- 4.98%, 19.20%
      +/- 2.98%, both P < 0.05) and the expressions of Notch-1, Jagged-1 and Hes-1 in
      SH-SY5Y cell. CONCLUSION: The activation of Notch signaling pathway plays an
      important role in MPP(+)-induced apoptosis of SH-SY5Y cell. DAPT inhibits Notch
      signaling pathway and protects SH-SY5Y cell from MPP(+)-induced apoptosis.

PMID- 24851695
TI  - [Curcumin improves the impaired working memory in cerebral ischemia-reperfusion
      rats by inhibiting proinflammatory cytokines].
AB  - OBJECTIVE: To investigate the ameliorative effect of curcumin pretreatment
      against impaired spatial working memory on global cerebral ischemia-reperfusion
      rats and to explore its mechanism. METHODS: After trained on a modified T-maze,
      120 adult SD rats were randomly divided into 5 groups: sham group (S group),
      cerebral ischemia-reperfusion group (IR group), curcumin group (C group), LPS
      group (L group) and curcumin+LPS group (C+L group). Rats were treated with drugs
      or vehicles 1 h before 10 min global cerebral ischemia. Six rats in each group 7
      days after reperfusion were tested in T-maze. Six rats in each group were
      sacrificed at 2 h, 1, 3 and 7 d after reperfusion and their serum or brains were
      harvested. Brain sections were stained with HE or toluidine blue and neuronal
      damage was quantified by the average neuronal density of CA1 area.
      Immunohistochemical staining for hippocampal IL-1beta and TNF-alpha was carried
      out, levels of serum IL-1beta and TNF-alpha was detected using ELISA procedure.
      RESULTS: Compared with S group, percentage of T-maze correct responses was
      decreased (88% +/- 12% vs 69% +/- 8%, P < 0.05), an extensive pyramidal neurons
      loss in CA1 area was observed, level of IL-1beta (0.26 +/- 0.04 vs 0.53 +/- 0.06,
      P < 0.05;48 +/- 13 vs 161 +/- 31, P < 0.05) and TNF-alpha (40.244 +/- 0.025 vs
      0.418 +/- 0.036, P < 0.05; 33 +/- 4 vs 85 +/- 15, P < 0.05) in hippocampi or
      serum was increased in IR group. Compared with IR group, percentage of T-maze
      correct responses was increased (78% +/- 13%) and average pyramidal neuronal
      density in CA1 area was increased with an decrease in hippocampi or serum IL
      1beta (0.44 +/- 0.09, 72 +/- 19) and TNF-alpha (0.307 +/- 0.047, 57 +/- 14) in C
      group(P < 0.05). Compared with IR group, percentage of T-maze correct responses
      (61% +/- 6%) was decreased with IL-1beta (0.86 +/- 0.13, 331 +/- 51), TNF-alpha
      (0.735 +/- 0.059, 185 +/- 20) in hippocampi and serum was increased in L group (P
      < 0.05). Compared with L group, percentage of T-maze correct responses (69% +/-
      12%) and average pyramidal neuronal density in CA1 area was increased with IL
      1beta (0.69 +/- 0.09, 246 +/- 24), TNF-alpha(0.586 +/- 0.047, 105 +/- 25) in
      hippocampi and serum was decreased in C+L group (P < 0.05). CONCLUSION: Curcumin
      pretreatment improves the impaired spatial working memory in global cerebral
      ischemia-reperfusion rats by inhibiting proinflammatory cytokines.

PMID- 24851696
TI  - Association of perceived stress with depressive symptoms in older Taiwanese:
      Results of a population-based study.
AB  - AIMS: We determined the association of perceived stress with depressive symptoms
      in older Taiwanese. METHODS: We analyzed the 2007 dataset of the Taiwan
      Longitudinal Survey on Aging, a population-based survey of 4534 persons aged >=54
      years. Perceived stress was based on respondents' reports of whether each of the
      five situations (own health, financial status, job, getting along with family
      members and family members' problems) "makes you feel stressed or anxious".
      Participants were rated with the 10-item Center for Epidemiologic Studies
      Depression scale (score 0-30; >=10 as having depressive symptoms). Multivariate
      logistic regression analysis was carried out to determine the association of each
      perceived stress situation with depressive symptoms in persons aged 54-64 years
      (middle-aged), 65-74 years (young-old) and >=75 years (old-old). RESULTS: Over
      one-third of respondents were stressed over their own health. The middle-aged
      respondents who were stressed were 2.0-10.9-fold as likely to have depressive
      symptoms, the young-old were 3.1-8.1-fold as likely and the old-old were 4.3-12.6
      fold as likely compared with the non-stressed respondents (all P < 0.001).
      Financial stress and its association with depressive symptoms deceased with
      increasing age. Nearly half of the Taiwanese older adults had concerns over
      family members' problems and the concern was associated with depressive symptoms
      in the younger age groups. Relationship strain with family members existed in
      <10% of older Taiwanese, but the association with depressive symptoms was strong.
      Job-related stress was not associated with depressive symptoms. CONCLUSIONS:
      Perceived stress and its association with depressive symptoms vary according to
      stress situations and age. The present findings should be useful for developing
      appropriate strategies to reduce the risk of depression in older adults.

PMID- 24851697
TI  - Diagnostic value of clinical tests for degenerative rotator cuff disease in
      medical practice.
AB  - OBJECTIVES: To assess the diagnostic value of clinical tests for degenerative
      rotator cuff disease (DRCD) in medical practice. METHODS: Patients with DRCD were
      prospectively included. Eleven clinical tests of the rotator cuff have been done.
      One radiologist performed ultrasonography (US) of the shoulder. Results of US
      were expressed as normal tendon, tendinopathy or full-thickness tear (the
      reference). For each clinical test and each US criteria, sensitivity,
      specificity, negative predictive value and positive predictive value, accuracy,
      negative likelihood ratio (NLR) and positive likelihood ratio (PLR) were
      calculated. Clinical relevance was defined as PLR >=2 and NLR <=0.5. RESULTS: For
      35 patients (39 shoulders), Jobe (PLR: 2.08, NLR: 0.31) and full-can (2, 0.5)
      test results were relevant for diagnosis of supraspinatus tears and resisted
      lateral rotation (2.42, 0.5) for infraspinatus tears, with weakness as response
      criteria. The lift-off test (8.50, 0.27) was relevant for subscapularis tears
      with lag sign as response criteria. Yergason's test (3.7, 0.41) was relevant for
      tendinopathy of the long head of the biceps with pain as a response criterion.
      There was no relevant clinical test for diagnosis of tendinopathy of
      supraspinatus, infraspinatus or subscapularis. CONCLUSIONS: Five of 11 clinical
      tests were relevant for degenerative rotator cuff disease.

PMID- 24851698
TI  - Intrathecal baclofen for dystonia treatment during pregnancy: A case report.

PMID- 24851699
TI  - Epigenetics and epilepsy.
AB  - INTRODUCTION: Epigenetics is the study of heritable modifications in gene
      expression that do not change the DNA nucleotide sequence. Some of the most
      thoroughly studied epigenetic mechanisms at present are DNA methylation, post
      transcriptional modifications of histones, and the effect of non-coding RNA
      molecules. Gene expression is regulated by means of these mechanisms and
      disruption of these molecular pathways may elicit development of diseases.
      DEVELOPMENT: We describe the main epigenetic regulatory mechanisms and review the
      most recent literature about epigenetic mechanisms and how those mechanisms are
      involved in different epileptic syndromes. CONCLUSION: Identifying the epigenetic
      mechanisms involved in epilepsy is a promising line of research that will deliver
      more in-depth knowledge of epilepsy pathophysiology and treatments.

PMID- 24851700
TI  - Cytotoxic effect of ergot alkaloids in Achnatherum inebrians infected by the
      Neotyphodium gansuense endophyte.
AB  - Ergonovine or ergonovinine was isolated from the aerial parts of endophyte
      (Neotyphodium gansuense) infected (E+) drunken horse grass (Achnatherum
      inebrians), neither of which existed in endophyte-free (E-) plants. Both of these
      ergot alkaloids had a cytotoxic effect on animal smooth muscle cells and
      increased cell growth inhibition with greater concentrations, in a significantly
      (P < 0.05) positive correlation. The median inhibitory concentrations (IC50) for
      ergonovine and ergonovinine were 71.95 and 72.75 MUg/mL, respectively. These
      results indicate that endophytic ergot alkaloids may be the cause of drunken
      horse grass poisoning. 

PMID- 24851701
TI  - Enhanced data generated with electrons (EDGE) special issue introduction.

PMID- 24851702
TI  - Magnesium availability regulates the development of root hairs in Arabidopsis
      thaliana (L.) Heynh.
AB  - Root hairs are reported to be plastic in response to nutrient supply, but
      relatively little is known about their development in response to magnesium (Mg)
      availability. Here, we showed that development of root hairs of Arabidopsis
      decreased progressively with increasing Mg supply, which was related to the
      initiation of new trichoblast files and likelihood of trichoblasts to form hairs.
      Tip-focused reactive oxygen species (ROS) and cytosolic Ca(2+) concentrations
      [(Ca(2+) )c] during elongation of root hairs were enhanced under low Mg but
      decreased under high Mg. Under low Mg, application of diphenylene iodonium (DPI)
      or BAPTA [1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid] blocked the
      enhanced development of root hairs and the opposite was true when the plants
      under high Mg were treated with phenazine methosulphate (PMS), methyl viologen
      (MV) or CaCl2 . Furthermore, Mg availability did not alter root hair growth in
      rhd2-1 mutant that contains lower levels of ROS and cytosolic [Ca(2+) ]c.
      Transcriptome data and qPCR results revealed a greater fraction of morphogenetic
      H-genes, and cell wall organization genes were up-regulated by low Mg but down
      regulated by high Mg. Our data suggest a profound effect of Mg supply on the
      development of root hairs in Arabidopsis, through the characterized Ca(2+) and
      ROS signals that modulate the elongation of root hairs and the expression of root
      hair morphogenetic genes.

PMID- 24851712
TI  - Improved soybean oil quality by targeted mutagenesis of the fatty acid desaturase
      2 gene family.
AB  - Soybean oil is high in polyunsaturated fats and is often partially hydrogenated
      to increase its shelf life and improve oxidative stability. The trans-fatty acids
      produced through hydrogenation pose a health threat. Soybean lines that are low
      in polyunsaturated fats were generated by introducing mutations in two fatty acid
      desaturase 2 genes (FAD2-1A and FAD2-1B), which in the seed convert the
      monounsaturated fat, oleic acid, to the polyunsaturated fat, linoleic acid.
      Transcription activator-like effector nucleases (TALENs) were engineered to
      recognize and cleave conserved DNA sequences in both genes. In four of 19
      transgenic soybean lines expressing the TALENs, mutations in FAD2-1A and FAD2-1B
      were observed in DNA extracted from leaf tissue; three of the four lines
      transmitted heritable FAD2-1 mutations to the next generation. The fatty acid
      profile of the seed was dramatically changed in plants homozygous for mutations
      in both FAD2-1A and FAD2-1B: oleic acid increased from 20% to 80% and linoleic
      acid decreased from 50% to under 4%. Further, mutant plants were identified that
      lacked the TALEN transgene and only carried the targeted mutations. The ability
      to create a valuable trait in a single generation through targeted modification
      of a gene family demonstrates the power of TALENs for genome engineering and crop
      improvement. 

PMID- 24851713
TI  - Humic acids-based hierarchical porous carbons as high-rate performance electrodes
      for symmetric supercapacitors.
AB  - Two kinds of hierarchical porous carbons (HPCs) with specific surface areas of
      2000 m(2)g(-1) were synthesized using leonardite humic acids (LHA) or
      biotechnology humic acids (BHA) precursors via a KOH activation process. Humic
      acids have a high content of oxygen-containing groups which enabled them to
      dissolve in aqueous KOH and facilitated the homogeneous KOH activation. The LHA
      based HPC is made up of abundant micro-, meso-, and macropores and in 6M KOH it
      has a specific capacitance of 178 F g(-1) at 100 Ag(-1) and its capacitance
      retention on going from 0.05 to 100 A g(-1) is 64%. In contrast, the BHA-based
      HPC exhibits a lower capacitance retention of 54% and a specific capacitance of
      157 F g(-1) at 100 A g(-1) which is due to the excessive micropores in the BHA
      HPC. Moreover, LHA-HPC is produced in a higher yield than BHA-HPC (51 vs. 17
      wt%).

PMID- 24851714
TI  - Resilience in families with a child with cancer.
AB  - The aim of this study was to identify and explore resilience factors associated
      with family adaption after a child had been diagnosed with cancer. Using a cross
      sectional survey research design, parents (n = 26), and children (n = 25) from
      the same families independently completed six self-report questionnaires, as well
      as responded to an open-ended question about those qualities that helped their
      family through the period following the diagnosis. The most significant results
      came from the children's data. According to these results, connectedness within
      the family, the experience of control over life events, family routines,
      positive, and supportive communication, redefinition of crisis situations, and
      lastly, a passive appraisal of crisis situations, were positively linked to
      better family adaptation. The identified factors should be strengthened and
      developed in families finding themselves in a similar situation. 

PMID- 24851715
TI  - Widespread erythema ab igne caused by hot bathing.

PMID- 24851718
TI  - Enteric reconstruction of pancreatic stump following pancreaticoduodenectomy: a
      review of the literature.
AB  - Techniques for reconstruction of pancreatic stump with gastrointestinal tract
      following pancreaticoduodenectomy are closely related to postoperative
      complications, mortality and quality of life. In order to reduce postoperative
      complications, particularly pancreatic fistula, many modifications and new
      surgical techniques have been proposed to replace the traditional
      pancreaticojejunostomy and pancreaticogastrostomy. The objective of this review,
      based on large prospective randomized trials and meta-analyses, is to evaluate
      the different techniques of enteric reconstruction of pancreatic stump following
      pancreaticoduodenectomy, including: invagination pancreaticojejunostomy, binding
      pancreaticojejunostomy, duct-to-mucosa pancreaticojejunostomy, Roux-en-Y
      pancreaticojejunostomy, and pancreaticogastrostomy, so as to provide a
      comprehensive comparison of these techniques and to assess of their roles and
      effectiveness. 

PMID- 24851717
TI  - IL-1beta-induced, matrix metalloproteinase-3-regulated proliferation of embryonic
      stem cell-derived odontoblastic cells is mediated by the Wnt5 signaling pathway.
AB  - We previously established a method for differentiating induced pluripotent stem
      cells and embryonic stem (ES) cells into alpha2 integrin-positive odontoblast
      like cells. We also reported that interleukin (IL)-1beta induces matrix
      metalloproteinase (MMP)-3-regulated cell proliferation and suppresses apoptosis
      in these cells, suggesting that MMP-3 plays a potentially unique physiological
      role in the regeneration of odontoblast-like cells. Here, we examined whether up
      regulation of MMP-3 activity by IL-1beta was mediated by Wnt signaling and led to
      increased proliferation of odontoblast-like cells. IL-1beta increased mRNA and
      protein levels of Wnt5a, Wnt5b and the Wnt receptor Lrp5. Exogenous Wnt5a and
      Wnt5b were found to increase MMP-3 mRNA, protein and activity, and interestingly
      the rate of proliferation in these cells. Treatment with siRNAs against Wnt5a,
      Wnt5b and Lrp5 suppressed the IL-1beta-induced increase in MMP-3 expression and
      suppressed cell proliferation, an effect rescued by application of exogenous
      Wnt5. These results demonstrate the sequential involvement of Wnt5, Lrp5 and MMP
      3 in effecting IL-1beta-induced proliferation of ES cell-derived odontoblast-like
      cells.

PMID- 24851720
TI  - Organics Exposure in Orbit (OREOcube): A next-generation space exposure platform.
AB  - The OREOcube (ORganics Exposure in Orbit cube) experiment on the International
      Space Station (ISS) will investigate the effects of solar and cosmic radiation on
      organic thin films supported on inorganic substrates. Probing the kinetics of
      structural changes and photomodulated organic-inorganic interactions with real
      time in situ UV-visible spectroscopy, this experiment will investigate the role
      played by solid mineral surfaces in the (photo)chemical evolution, transport, and
      distribution of organics in our solar system and beyond. In preparation for the
      OREOcube ISS experiment, we report here laboratory measurements of the
      photostability of thin films of the 9,10-anthraquinone derivative anthrarufin (51
      nm thick) layered upon ultrathin films of iron oxides magnetite and hematite (4
      nm thick), as well as supported directly on fused silica. During irradiation with
      UV and visible light simulating the photon flux and spectral distribution on the
      surface of Mars, anthrarufin/iron oxide bilayer thin films were exposed to CO2
      (800 Pa), the main constituent (and pressure) of the martian atmosphere. The time
      dependent photodegradation of anthrarufin thin films revealed the inhibition of
      degradation by both types of underlying iron oxides relative to anthrarufin on
      bare fused silica. Interactions between the organic and inorganic thin films,
      apparent in spectral shifts of the anthrarufin bands, are consistent with
      presumed free-electron quenching of semiquinone anion radicals by the iron oxide
      layers, effectively protecting the organic compound from photodegradation.
      Combining such in situ real-time kinetic measurements of thin films in future
      space exposure experiments on the ISS with postflight sample return and analysis
      will provide time-course studies complemented by in-depth chemical analysis. This
      will facilitate the characterization and modeling of the chemistry of organic
      species associated with mineral surfaces in astrobiological contexts. 

PMID- 24851719
TI  - A comparative study on two different pathological methods to retrieve lymph nodes
      following gastrectomy.
AB  - BACKGROUND: The number of lymph nodes harvested during gastrectomy depends on the
      extension of lymphadenectomy and the method of lymph node retrieval. AIM: The
      objective of this study was to evaluate two methods of lymph node retrieval in
      specimens of gastric cancer. METHODS: The number of lymph nodes was compared
      using two different techniques. The technique used in the first group was manual
      dissection following formalin fixation, and the techniques used in the second
      group was fat-clearing by acetone. RESULTS: Both groups were comparable for
      demographic and pathological variables. The average number of harvested nodes was
      19.3 +/- 10 for the manual group as compared to 26.1 +/- 14 in the acetone group
      (P = 0.003). The differences in the average number of positive nodes did not
      reach statistical significance (4.6 compared to 6.9 nodes). CONCLUSION: The
      acetone clearing technique enables the evaluation of a larger number of nodes. An
      increase, but statistically non significant, number of positive nodes was noted
      in the acetone group.

PMID- 24851721
TI  - Fluorescence aptameric sensor for isothermal circular strand-displacement
      polymerization amplification detection of adenosine triphosphate.
AB  - In this work, isothermal circular strand-displacement polymerization
      amplification assay is developed for highly specific and sensitive detection of
      adenosine triphosphate (ATP). The amplification process consists of circular
      common target molecule-displacement polymerization (CCDP) and circular nucleic
      acid strand-displacement polymerization (CNDP). In the presence of ATP, the
      complementary strand was released from the aptamer by the target recognition of
      ATP, and catalyzed the subsequent cycle reaction. With the polymerase and primer,
      the displaced target triggers the process of CCDP. With the involvement of
      nicking endonuclease, the released complementary strand triggers the CNDP.
      Combined CCDP with CNDP, the exponentially produced fluorescence probes are
      obtained, achieving a detection limit of ATP as low as 2.6 * 10(-10)M. Moreover,
      the proposed strategy exhibits an excellent specificity and is successfully
      applied in real sample assay which demonstrates potential application in
      practical samples.

PMID- 24851722
TI  - Time-dependent migratory behaviors in the long-term studies of fibroblast
      durotaxis on a hydrogel substrate fabricated with a soft band.
AB  - Durotaxis, biased cell movement up a stiffness gradient on culture substrates, is
      one of the useful taxis behaviors for manipulating cell migration on engineered
      biomaterial surfaces. In this study, long-term durotaxis was investigated on
      gelatinous substrates containing a soft band of 20, 50, and 150 MUm in width
      fabricated using photolithographic elasticity patterning; sharp elasticity
      boundaries with a gradient strength of 300 kPa/50 MUm were achieved. Time
      dependent migratory behaviors of 3T3 fibroblast cells were observed during a time
      period of 3 days. During the first day, most of the cells were strongly repelled
      by the soft band independent of bandwidth, exhibiting the typical durotaxis
      behavior. However, the repellency by the soft band diminished, and more cells
      crossed the soft band or exhibited other mixed migratory behaviors during the
      course of the observation. It was found that durotaxis strength is weakened on
      the substrate with the narrowest soft band and that adherent affinity-induced
      entrapment becomes apparent on the widest soft band with time. Factors, such as
      changes in surface topography, elasticity, and/or chemistry, likely contributing
      to the apparent diminishing durotaxis during the extended culture were examined.
      Immunofluorescence analysis indicated preferential collagen deposition onto the
      soft band, which is derived from secretion by fibroblast cells, resulting in the
      increasing contribution of haptotaxis toward the soft band over time. The
      deposited collagen did not affect surface topography or surface elasticity but
      did change surface chemistry, especially on the soft band. The observed time
      dependent durotaxis behaviors are the result of the mixed mechanical and chemical
      cues. In the studies and applications of cell migratory behavior under a
      controlled stimulus, it is important to thoroughly examine other (hidden)
      compounding stimuli in order to be able to accurately interpret data and to
      design suitable biomaterials to manipulate cell migration. 

PMID- 24851724
TI  - Adolescents' perceptions of peers with depression: an attributional analysis.
AB  - Understanding adolescents' perceptions of peers with depression is vital in order
      to tackle peer exclusion and lessen stigmatization. To examine adolescents'
      perceptions of a hypothetical peer with depression, we test an attributional
      model: that stigma towards persons with mental disorders is influenced by
      attributions about the causes of their disorders and inferences of personal
      responsibility. Participants were 401 adolescents from 4th year/10th grade with
      an age range of 14.75-17.08 years (M=15.90 years; S.D.=0.403 years). Structural
      Equation Modeling was employed to assess the relationships among causal
      attributions (personal control), perceived responsibility, and emotional
      reactions, in predicting social acceptance/exclusion of a peer with depression.
      Results indicated that (a) if the peer with depression is perceived as having
      little control over the cause of depression, responsibility is not inferred,
      participants feel sympathy and pity, and are likely to socially accept the peer
      (b) gender of vignette character and participant influence these responses. This
      study builds on our theoretical understanding of why adolescents with depression
      may face social exclusion from peers by applying a well-established theory in
      social psychology. Findings should be incorporated into the design of
      interventions aimed at reducing peer exclusion and stigmatization of adolescents
      with depression. 

PMID- 24851723
TI  - Trajectory of care and use of multimodality therapy in older patients with
      pancreatic adenocarcinoma.
AB  - INTRODUCTION: Multimodality therapy with chemotherapy and operative resection is
      recommended for patients with locoregional pancreatic cancer but is not received
      by many patients. OBJECTIVE: To evaluate patterns in the use and timing of
      chemotherapy and resection and factors associated with receipt of multimodality
      therapy in older patients with locoregional pancreatic cancer. METHODS: We used
      Surveillance, Epidemiology, and End Results-linked Medicare data (1992-2007) to
      identify patients with locoregional pancreatic adenocarcinoma. Multimodality
      therapy was defined as receipt of both chemotherapy and pancreatic resection.
      Logistic regression was used to determine factors independently associated with
      receipt of multimodality therapy. Log-rank tests were used to identify
      differences in survival for patients stratified by type and timing of treatment.
      RESULTS: We identified 10,505 patients with pancreatic adenocarcinoma. 5,358
      patients (51.0%) received either chemotherapy or surgery, with 1,166 patients
      (11.1%) receiving both modalities. Resection alone was performed in 1,138
      patients (10.8%), and chemotherapy alone was given to 3,054 (29.1%) patients. In
      patients undergoing resection as the initial treatment modality, 49.4% never
      received chemotherapy; 97.4% of patients who underwent chemotherapy as the
      initial treatment modality never underwent resection. The use of multimodality
      therapy increased from 7.4% of patients in 1992-1995 to 13.8% of patients in 2004
      2007 (P < .0001). The 2-year survival was 41.0% for patients receiving
      multimodality therapy, 25.1% with resection alone, and 12.5% with chemotherapy
      alone (P < .0001). Of the patients receiving multimodality therapy, chemotherapy
      was delivered in the adjuvant setting in 93.1% and in the neoadjuvant setting in
      6.9%, with similar 2-year survival with either approach (neoadjuvant vs adjuvant,
      46.9% vs 40.6%; P = .16). Year of diagnosis, white race, less comorbidity, and no
      vascular invasion were independently associated with receipt of multimodality
      therapy. CONCLUSION: Only half of older patients with locoregional pancreatic
      cancer receive any treatment, and fewer than one quarter of treated patients
      receive multimodality therapy. Nearly all patients receiving chemotherapy as the
      initial treatment modality did not undergo resection, whereas half of those
      undergoing resection first received chemotherapy. When multimodality therapy is
      used, the vast majority of patients had chemotherapy in the adjuvant setting with
      a similar survival, regardless of approach.

PMID- 24851725
TI  - Neuropsychological functioning in adolescents and young adults with major
      depressive disorder--a review.
AB  - While neuropsychological dysfunction is a contributor to major depressive
      disorder (MDD) in adult MDD, little is known about neuropsychological function in
      MDD during adolescence and early adulthood. The aim of this review is to evaluate
      literature on neuropsychological function in this young age group. A database
      search of Medline, the Cochrane database and PsycInfo was conducted.
      Inclusion/exclusion criteria yielded seven case-control studies on
      neuropsychological functioning in MDD (12-25 years of age) published since 1995.
      Effect sizes were calculated. Results show a broader range of statistically
      significant neuropsychological deficits in MDD compared to controls in the
      cognitive domains of executive function (EF), working memory (WM), psychomotor
      and processing speed (PPS), verbal fluency (VF) and visual (-spatial) memory
      (VM). Most convincingly, three out of four studies investigating WM and three out
      of four studies investigating PPS found statistically significant impairments in
      MDD with varying effect sizes. EF deficits were reported only in three out of
      seven studies with small, medium and large effect sizes. While some evidence was
      found for impaired VM and VF, no evidence was observed for attention and verbal
      learning and memory; however, these domains have been less extensively studied.
      Further research is required to broaden the study base. 

PMID- 24851726
TI  - Antiplatelet and anticoagulative medication during shockwave lithotripsy.
AB  - BACKGROUND AND PURPOSE: Shockwave lithotripsy (SWL) is the gold standard
      treatment of patients with most renal and proximal ureteral calculi. Severe
      bleeding complications in SWL are extremely rare. Uncorrected bleeding diathesis
      might increase the risk and is considered to be an absolute contraindication for
      SWL. Perioperative management of anticoagulative and antiplatelet therapy has
      changed in the recent past. In particular, low-dose acetylsalicylic acid (ASA) is
      no longer a contraindication for many surgical procedures. METHODS: A systematic
      Medline/PubMed literature search of peer-reviewed scientific articles in urology
      and cardiovascular medicine was performed concerning the management of
      anticoagulative and antiplatelet medication during SWL. RESULTS: The literature
      on medically acquired and pathological bleeding diathesis and SWL in general is
      rare, retrospective, nonstandardized, and of low quality. Routine cessation of
      obligatory indicated anticoagulative or antiplatelet medication implies a
      significant risk for cardiovascular adverse events (CAE). Ureterorenoscopy is
      recommended in patients with uncorrected bleeding diathesis, although this is not
      based on high-level evidence. CONCLUSION: In patients with obligatory intake of
      anticoagulative or antiplatelet medication, the risk for CAE must be balanced
      against the SWL-induced bleeding risk. In patients with low-dose ASA-intake, SWL
      should be considered as an option instead of being disregarded as an absolute
      contraindication. Prospective randomized trials designed to define the optimal
      management of anticoagulants and antiplatelets during SWL are warranted.

PMID- 24851727
TI  - Breakthrough ideas leading to new futures: next steps.
AB  - In 2010, the educational International Surgical Wound Forum (ISWF) was created to
      facilitate discussion among global experts regarding modern wound treatment
      challenges and how negative pressure wound therapy (NPWT) could be used to
      address those challenges. This is the second of two supplements, which are based
      on 2012 and 2013 ISWF presentations and demonstrate the evolution of NPWT's role
      in wound care. The previous supplement provided an overview of critical health
      care issues and current clinical practice and reviewed evidence and experience
      using NPWT with instillation of topical wound solutions. This supplement presents
      clinical experience using negative pressure over closed surgical incisions, in
      the open abdomen, and in wounds with enteroatmospheric fistulas.

PMID- 24851728
TI  - Value of incisional negative pressure wound therapy in orthopaedic surgery.
AB  - Soft tissue and wound treatment after orthopaedic interventions (especially after
      trauma) is still an enormously challenging situation for every surgeon. Since
      development of negative pressure wound therapy (NPWT), new indications have been
      consistently added to the original field of application. Recently, NPWT has been
      applied directly over high-risk closed surgical incisions. Review of the
      literature indicates that this therapy has shown positive effects on incisions
      after total ankle replacement or calcaneal fractures, preventing haematoma and
      wound dehiscence. In those cases reduced swelling, decreased pain and healing
      time of the wound were seen. Additionally, NPWT applied on incisions after
      acetabular fractures showed a decreased rate of infection and wound healing
      problems compared with published infection rates. Even after total hip
      arthroplasty, incisional NPWT reduced incidence of postoperative seroma and
      improved wound healing. In patients with tibial plateau, pilon or calcaneus
      fractures requiring surgical stabilisation after blunt trauma, reduced risk of
      developing acute and chronic wound dehiscence and infection was observed when
      using incisional NPWT. To conclude, incisional NPWT can help to reduce risk of
      delayed wound healing and infection after severe trauma and orthopaedic
      interventions.

PMID- 24851730
TI  - The use of a surgical incision management system on vascular surgery incisions: a
      pilot study.
AB  - Health care-associated infections in hospitals, including surgical site
      infections, contribute significantly to morbidity as well as mortality. Surgical
      incision management (SIM) using negative pressure wound therapy (PrevenaTM
      Incision Management System, Kinetic Concepts, Inc., San Antonio, TX, USA) is
      designed to cover and protect closed surgical incisions from external factors
      including infectious sources and local trauma, while negative pressure removes
      fluid and infectious material from the surgical incision. A prospective case
      control study assessed wound complications in patients undergoing vascular bypass
      procedures, where both femoral areas were incised to gain access to the femoral
      arteries. SIM was placed on one femoral area while a standard postoperative wound
      dressing was placed on the contralateral femoral area. Eight patients were
      included in this pilot study. All of them required bilateral femoral artery
      access. During the follow-up period patients were monitored for wound
      complications. All wound complications requiring surgical intervention were
      considered significant. No significant wound complications occurred in wounds
      treated with SIM, compared with three significant complications in control
      wounds. These preliminary data would suggest a potential reduction in wound
      complications and no observed increase in haemorrhage in high-risk patients with
      severe co-morbidities undergoing vascular surgery.

PMID- 24851729
TI  - Effect of surgical incision management on wound infections in a poststernotomy
      patient population.
AB  - Skin breakdown and infiltration of skin flora are key causative elements in
      poststernotomy wound infections. We hypothesised that surgical incision
      management (SIM) using negative pressure wound therapy over closed surgical
      incisions for 6-7 days would reduce wound infections in a comprehensive
      poststernotomy patient population. 'All comers' undergoing median sternotomy at
      our institution were analysed prospectively from 1 September to 15 October 2013
      (study group, n = 237) and retrospectively from January 2008 to December 2009
      (historical control group, n = 3508). The study group had SIM (PrevenaTM Therapy)
      placed immediately after skin suturing and applied at -125 mmHg for 6-7 days,
      whereas control group received conventional sterile wound tape dressings. Primary
      endpoint was wound infection within 30 days. Study group had a significantly
      lower infection rate than control group: 1.3% (3 patients) versus 3.4% (119
      patients), respectively (P < 0.05; odds ratio 2.74). In the study group, when the
      foam dressing was removed after 6-7 days, the incision was primarily closed in
      234 of 237 patients (98.7%). SIM over clean, closed incisions for the first 6-7
      postoperative days significantly reduced the incidence of wound infection after
      median sternotomy. Based on these data SIM may be cost-effective in patients
      undergoing cardiac surgery.

PMID- 24851731
TI  - The open abdomen: temporary closure with a modified negative pressure therapy
      technique.
AB  - The most common indications for an open abdomen (OA) are abdominal compartment
      syndrome, damage control surgery, diffuse peritonitis and wound dehiscence, and
      often require a temporary abdominal closure (TAC). The different TAC methods that
      are currently available include skin closure techniques, mesh products and
      negative pressure therapy (NPT) systems. For this study, we retrospectively
      reviewed records of 115 OA patients treated with the commercially available NPT
      systems (V.A.C.((r)) Abdominal Dressing System and ABTheraTM Open Abdomen
      Negative Pressure Therapy System) using a new method of applying the system - the
      narrowing technique - over a 5-year period. Endpoints included fascial closure
      and 30-day mortality rates and presence of enteroatmospheric fistulas. Secondary
      closure of the fascia was obtained in 92% (106/115) of the patients with a
      mortality rate of 17% (20/115) and a fistula rate of 3.5% (4/115). The use of the
      narrowing technique to apply NPT may explain the high closure rates observed in
      the patient population of this study. Further studies are necessary to compare
      the different methods and to evaluate the long-term outcomes. 

PMID- 24851732
TI  - Management of enteroatmospheric fistulae.
AB  - A small-bowel enteroatmospheric fistula (EAF) is an especially challenging
      complication for patients with open abdomens (OAs) and their surgeons.
      Manipulation of the bowel during treatment (e.g. dressing changes) is one of the
      risk factors for developing these openings between the atmosphere and the
      gastrointestinal tract. Unlike enterocutaneous fistulae, EAFs have neither
      overlying soft tissue nor a real fistula tract, which reduces the likelihood of
      their spontaneous closure. Surgical closure is necessary but not always easy to
      do in the OA environment. Negative pressure wound therapy (NPWT) has been used
      successfully as an adjunct therapy to heal the wound around EAFs. This review
      discusses many aspects of managing EAFs in patients with OAs, and presents
      techniques that have been developed to isolate the fistula and divert effluent
      while applying NPWT to the surrounding wound bed.

PMID- 24851733
TI  - A simple novel technique for enteroatmospheric fistulae: silicone fistula plug.
AB  - Enteroatmospheric fistulae (EAFs), a rare condition that develops in patients
      treated with an open abdomen, present serious problems for the surgeon. There are
      no fixed algorithms for treatment of EAF, and treatment options are determined
      based on the experience of the surgeon and status of the patient. We developed a
      'suspended silicone fistula plug' for treating a patient who developed an EAF
      after undergoing multiple operations in a short period of time. Used in
      conjunction with negative pressure wound therapy, application of this novel
      therapy resulted in EAF closure and patient discharge.

PMID- 24851734
TI  - Use of self-expanding covered stent and negative pressure wound therapy to manage
      late rectal perforation after injury from an improvised explosive device: a case
      report.
AB  - Blast injuries, caused by explosions accompanied by high-pressure waves, produce
      tissue damage in the acute period, followed in the later period by circulatory
      disorders due to vascular endothelial damage and related tissue necrosis. Blunt
      rectal perforation is rare and difficult to diagnose. In the acute period
      following blast pelvic injuries, the main objectives are to stop bleeding,
      minimise contamination and preserve the patient's life. The patient in this
      report had major vascular injuries, severe pelvic injury and, in the later
      period, rectal perforation because of vascular endothelial damage caused by the
      blast effect. Our aim was to treat the patient conservatively because of his poor
      general condition. We placed a self-expanding covered stent (SECS) into the
      rectum and then applied negative pressure wound therapy (NPWT; V.A.C.(r) Therapy,
      KCI) to the pelvic region and perirectal area. At the end of the treatment, the
      rectal perforation was closed, and the patient was discharged with healing. In
      this article, we discuss the novel use of an SECS with NPWT and review related
      literature.

PMID- 24851735
TI  - Vertebral compression fracture rules.

PMID- 24851736
TI  - Minimally invasive versus open laminotomy.

PMID- 24851737
TI  - Evidence-based guidelines improperly assessed epidural injections.

PMID- 24851738
TI  - Letter to the editor regarding Mannion, Brox, Fairbank. Comparison of spinal
      fusion and nonoperative treatment in patients with chronic low back pain: long
      term follow-up of three randomized controlled trials.

PMID- 24851739
TI  - Letter to the editor regarding Smuck M, Cristostomo RA, Demirjian R, et al.
      Morphologic change in the lumbar spine after lumbar medial branch radiofrequency
      neurotomy: a quantitative radiological study.

PMID- 24851740
TI  - Reply to letter to the editor "Morphologic changes in the lumbar spine following
      lumbar medial branch radiofrequency neurotomy: a quantitative radiologic study".

PMID- 24851741
TI  - Pathomechanism of intravertebral clefts in osteoporotic compression fractures of
      the spine: basivertebral foramen collapse might cause intravertebral avascular
      necrosis.

PMID- 24851742
TI  - Letter to the editor regarding: "Effectiveness of local vancomycin powder to
      decrease surgical site infections: a meta-analysis" by Chiang et al.

PMID- 24851743
TI  - A commentary on cervical spondylolysis in the contact athlete.

PMID- 24851745
TI  - Major histocompatibility complex class II alleles and haplotypes associated with
      non-suppurative meningoencephalitis in greyhounds.
AB  - Non-suppurative meningoencephalitis is a breed-restricted canine
      neuroinflammatory disorder affecting young greyhounds in Ireland. A genetic risk
      factor is suspected because of the development of disease in multiple siblings
      and an inability to identify a causative infectious agent. The aim of this study
      was to examine potential associations between dog leucocyte antigen (DLA) class
      II haplotype and the presence of the disease. DLA three locus haplotypes were
      determined in 31 dogs with non-suppurative meningoencephalitis and in 115 healthy
      control dogs using sequence-based typing (SBT) methods. All dogs were unrelated
      at the parental level. Two haplotypes (DRB1*01802/DQA1*00101/DQB1*00802 and
      DRB1*01501/DQA1*00601/DQB1*02201) were significantly (P = 0.0099 and 0.037)
      associated with the presence of meningoencephalitis, with odds ratios (95%
      confidence interval) of 5.531 (1.168-26.19) and 3.736 (1.446-9.652),
      respectively. These results confirm that there is an association between DLA
      class II haplotype and greyhound meningoencephalitis, suggesting an immunogenetic
      risk factor for the development of the disease. Greyhound meningoencephalitis may
      be a suitable model for human neuroinflammatory diseases with an immunogenetic
      component. 

PMID- 24851744
TI  - A new marker of sepsis post burn injury?*.
AB  - OBJECTIVES: Accurate diagnosis of sepsis is difficult in patients post burn due
      to the large inflammatory response produced by the major insult. We aimed to
      estimate the values of serum N-terminal pro-B-type natriuretic peptide and
      procalcitonin and the changes in hemodynamic variables as markers of sepsis in
      critically ill burn patients. DESIGN: Prospective, observational study. SETTING:
      A quaternary-level university-affiliated ICU. PATIENTS: Fifty-four patients with
      burns to total body surface area of greater than or equal to 15%, intubated with
      no previous cardiovascular comorbidities, were enrolled. INTERVENTIONS: At
      admission, a FloTrac/Vigileo system was attached and daily blood samples taken
      from the arterial catheter. Infection surveillance was carried out daily with
      patients classified as septic/nonseptic according to American Burns Consensus
      criteria. MEASUREMENTS AND MAIN RESULTS: N-terminal pro-B-type natriuretic
      peptide, procalcitonin, and waveform analysis of changes in stroke volume index
      and systemic vascular resistance index were measured within the first 24 hours
      after burn and daily thereafter for the length of the ICU stay or until their
      first episode of sepsis. Prevalences of stroke volume variation less than 12%
      (normovolemia) with hypotension (systolic blood pressure < 90 mm Hg) were
      recorded. Patients with sepsis differed significantly from "no sepsis" for N
      terminal pro-B-type natriuretic peptide, systemic vascular resistance index, and
      stroke volume index on days 3-7. Procalcitonin did not differ between sepsis and
      "no sepsis" except for day 3. Area under the receiver operating characteristic
      curves showed excellent discriminative power for B-type natriuretic peptide (p =
      0.001; 95% CI, 0.99-1.00), systemic vascular resistance index (p < 0.001; 95% CI,
      0.97-0.99), and stroke volume index (p < 0.01; 95% CI, 0.96-0.99) in predicting
      sepsis but not for procalcitonin (not significant; 95% CI, 0.29-0.46). A chi
      square crosstab found that there was no relationship between hypotension with
      normovolemia (stroke volume variation < 12%) and sepsis. CONCLUSIONS: Serum N
      terminal pro-B-type natriuretic peptide levels and certain hemodynamic changes
      can be used as an early indicator of sepsis in patients with burn injury.
      Procalcitonin did not assist in the early diagnosis of sepsis.

PMID- 24851746
TI  - Optimal resources for children's surgical care.
AB  - We will discuss a new initiative of the American College of Surgeons and the
      American Pediatric Surgical Association to prospectively define optimal resource
      standards for children's surgical care. 

PMID- 24851747
TI  - A survey-based assessment of the Canadian pediatric surgery workforce.
AB  - BACKGROUND: There is significant lack of information regarding the Canadian
      pediatric surgery workforce. METHODS: An IRB-approved survey aimed at assessing
      workforce issues was administered to pediatric surgeons and pediatric surgery
      chiefs in Canada in 2012. RESULTS: The survey was completed by 98% of practicing
      surgeons and 13 of the 18 division chiefs. Only 6% of surgeons are older than 60
      years, and only a fifth anticipate retirement over the next decade. The workforce
      is stable, with 82% of surgeons unlikely to change current positions. Surgical
      volume showed essentially no growth during the 5-year period 2006-2010. The
      majority of surgeons felt they were performing the right number or too few cases
      and anticipated minimal or no future growth in their individual practices or that
      of their group. Based on anticipated vacancies, the best estimate is a need for
      20 new pediatric surgeons over the next decade. This need is significantly
      surpassed by the current output from the Canadian training programs. CONCLUSIONS:
      The Canadian pediatric surgery workforce is currently saturated. The mismatch
      between the number of graduating trainees and the available positions over the
      next decade has significant repercussions for current surgery and pediatric
      surgery residents wishing to practice in Canada.

PMID- 24851748
TI  - ACS national surgical quality improvement program: targeting quality improvement
      in Canadian pediatric surgery.
AB  - PURPOSE: The pediatric NSQIP program is in the early stages of facilitated
      surgical quality improvement for children. The objective of this study is to
      describe the initial experience of the first Canadian Children's Hospital
      participant in this program. METHOD: Randomly sampled surgical cases from the
      "included" case list were abstracted into the ACS-NSQIP database. These surgical
      procedure-specific data incorporate patient risk factors, intraoperative details,
      and 30 day outcomes to generate annual reports which provide hierarchical ranking
      of participant hospitals according to their risk-adjusted outcomes. RESULTS: Our
      first risk-adjusted report identified local improvement opportunities based on
      our rates of surgical site infection (SSI) and urinary tract infection (UTI). We
      developed and implemented an engagement strategy for our stakeholders, performed
      literature reviews to identify practice variation, and conducted case control
      studies to understand local risk factors for our SSI/UTI occurrences. We have
      begun quality improvement activities targeting reduction in rates of SSI and UTI
      with our general surgery division and ward nurses, respectively. CONCLUSIONS: The
      NSQIP pediatric program provides high quality outcome data that can be used in
      support of quality improvement. This process requires multidisciplinary teamwork,
      systematic stakeholder engagement, clinical research methods and process
      improvement through engagement and culture change.

PMID- 24851749
TI  - Prenatal MRI fetal lung volumes and percent liver herniation predict pulmonary
      morbidity in congenital diaphragmatic hernia (CDH).
AB  - PURPOSE: The purpose of this study was to determine whether prenatal imaging
      parameters are predictive of postnatal CDH-associated pulmonary morbidity.
      METHODS: The records of all neonates with CDH treated from 2004 to 2012 were
      reviewed. Patients requiring supplemental oxygen at 30 days of life (DOL) were
      classified as having chronic lung disease (CLD). Fetal MRI-measured
      observed/expected total fetal lung volume (O/E-TFLV) and percent liver herniation
      (%LH) were recorded. Receiver operating characteristic (ROC) curves and
      multivariate regression were applied to assess the prognostic value of O/E-TFLV
      and %LH for development of CLD. RESULTS: Of 172 neonates with CDH, 108 had fetal
      MRIs, and survival was 76%. 82% (89/108) were alive at DOL 30, 46 (52%) of whom
      had CLD. Neonates with CLD had lower mean O/E-TFLV (30 vs.42%; p=0.001) and
      higher %LH (21.3+/-2.8 vs.7.1+/-1.8%; p<0.001) compared to neonates without CLD.
      Using ROC analysis, the best cutoffs in predicting CLD were an O/E-TFLV<35%
      (AUC=0.74; p<0.001) and %LH>20% (AUC=0.78; p<0.001). On logistic regression, O/E
      TFLV<35% and a %LH>20% were highly associated with indicators of long-term
      pulmonary sequelae. On multivariate analysis, %LH was the strongest predictor of
      CLD in patients with CDH (OR: 10.96, 95%CI: 2.5-48.9, p=0.002). CONCLUSION:
      Prenatal measurement of O/E-TFLV and %LH is predictive of CDH pulmonary morbidity
      and can aid in establishing parental expectations of postnatal outcomes.

PMID- 24851751
TI  - Prenatally-counseled congenital diaphragmatic hernia parents exhibit positive
      well-being before and after surgical repair.
AB  - BACKGROUND/PURPOSE: The purpose of this paper was to examine the effect of
      prenatal counseling in the Advanced Fetal Care Center (AFCC) on the well-being of
      parents of infants with congenital diaphragmatic hernia (CDH). METHODS: From 2008
      through 2012, 26 mothers and fathers of surgically repaired CDH patients who
      received prenatal counseling at our institution, and 15 who received no prenatal
      counseling, each completed the Short-Form 36 version 1 (SF-36v1) at the
      appropriate time points: prenatal, two weeks, and six months post-surgery.
      RESULTS: Parents in both groups did not differ by demographic characteristics.
      Patients who received prenatal counseling had significantly longer ventilatory
      time and length of stay (LOS) in the ICU and in the hospital compared to those
      who did not receive prenatal counseling (all P<.01). Mothers and fathers had
      similar SF-36v1 mental and physical component summary (MCS, PCS) post-surgery
      scores when compared by counseling status. Prenatal MCS scores for mothers and
      fathers (47 vs. 41; P=.24) were similar to those at six months post-surgery (47
      vs. 47; P=.90). CONCLUSIONS: When hospital LOS was controlled between groups
      stratified by AFCC counseling status, MCS scores were comparable prenatally and
      were sustained at six months post-surgery for both parents. These findings may
      reflect the support services parents received beginning in the prenatal period.

PMID- 24851750
TI  - Minimally invasive versus open repair of Bochdalek hernia: a meta-analysis.
AB  - BACKGROUND: Diaphragmatic hernia can be repaired by open or minimally invasive
      surgery (MIS), although it is unclear which technique has better outcomes. Our
      objective was to compare the outcomes of these procedures in a systematic review
      and meta-analysis. METHODS: We sought all publications describing both techniques
      through MEDLINE, Embase, and CENTRAL. Our primary outcome of interest was
      recurrence. We conducted statistical analyses using Review Manager 5.2. RESULTS:
      We did not identify any randomized controlled trials. Our pooled estimate of
      results from 10 studies showed that total recurrence was higher after MIS (OR:
      2.81 [1.73, 4.56], p<0.001). Subgroup analyses indicated higher recurrence after
      MIS for patch repairs (OR: 4.29 [2.13, 8.67], p<0.001), but not for primary
      repairs. Operative time was longer for MIS (MD: 55.25 [40.21, 70.28], p<0.001),
      while postoperative ventilator time and postoperative mortality were higher after
      open surgery (MD: 1.33 [0.05, 2.62], p= 0.04; OR: 7.54 [3.36, 16.90], p<0.001,
      respectively). CONCLUSIONS: Recurrence rate is higher after MIS than open repair
      when a patch is used. Operative time is also longer with MIS. Poorer outcomes
      after open surgery may be a result of selection bias rather than surgical
      technique. Surgeons should carefully consider the potential morbidity associated
      with MIS when deciding on a repair method.

PMID- 24851752
TI  - Mainstem bronchial atresia: a lethal anomaly amenable to fetal surgical
      treatment.
AB  - PURPOSE: The purpose of this study was to review the unique imaging
      characteristics, prenatal course, and outcomes for fetuses with mainstem
      bronchial atresia (MBA). METHODS: The records of all patients referred for a
      fetal lung malformation from 2001 to 2012 and the medical literature were
      reviewed to identify cases of MBA. RESULTS: Of 129 fetuses evaluated, 3 were
      diagnosed prenatally with right-sided MBA. The first had a CCAM-volume ratio
      (CVR) of 9, hydrops, mirror syndrome, and preterm delivery of a nonviable fetus.
      The second (CVR 2.6) had ascites, preterm delivery at 34-weeks, and neonatal
      demise. The third fetus (CVR 5.7) presented with hydrops at 21-weeks, prompting
      fetal pneumonectomy. Postoperatively, hydrops resolved, and the contralateral
      lung grew dramatically, but preterm delivery occurred 3 weeks later. Ventilation
      could not be sustained, and the infant died. Four similar cases of MBA were in
      the literature, all right-sided. Two fetuses with hydrops delivered at 25-weeks
      and died immediately. One pregnancy was terminated. One fetus underwent
      pneumonectomy at 24-weeks but died intraoperatively. CONCLUSION: MBA is a rare
      and lethal lesion that must be distinguished from other right-sided lung masses.
      Fetal pneumonectomy can be performed with resolution of hydrops and compensatory
      contralateral lung growth, but remains limited by complications of preterm birth.

PMID- 24851753
TI  - Fetal MRI improves diagnostic accuracy in patients referred to a fetal center for
      suspected esophageal atresia.
AB  - PURPOSE: The purpose of this study was to describe prenatal imaging
      characteristics and outcomes of fetuses with suspected esophageal atresia (EA) in
      order to improve prenatal diagnosis, counseling, and management. METHODS: The
      medical records of all patients referred to our multidisciplinary fetal center
      for suspected EA from January 2003 to April 2013 were reviewed retrospectively.
      RESULTS: Thirty-three patients were referred with a prenatal diagnosis of
      possible EA. Following fetal center evaluation with MRI, EA was deemed unlikely
      in 6 (18%) fetuses. Of 27 fetuses in whom EA could not be excluded, EA was
      confirmed postnatally in 15 (56%), excluded in 7 (26%), and unconfirmed in 5 (3
      fetal losses; 2 lost to follow-up). Imaging characteristics on fetal MRI
      associated with the highest positive predictive values (PPV) were an esophageal
      pouch (100%) and a small stomach (75%). The finding of polyhydramnios had high
      sensitivity (93%) but low specificity (31%) and PPV (61%) for a diagnosis of EA.
      CONCLUSION: Prenatal imaging and fetal center evaluation correctly identify the
      presence or absence of esophageal atresia in 78% of patients referred on
      suspicion of this condition. The presence of an esophageal pouch on fetal MRI has
      significant predictive value for EA. These data may assist with evidence-based
      prenatal family counseling.

PMID- 24851754
TI  - Post-operative management of esophageal atresia-tracheoesophageal fistula and
      gastroesophageal reflux: a Canadian Association of Pediatric Surgeons annual
      meeting survey.
AB  - BACKGROUND: Esophageal atresia (EA), with or without tracheoesophageal fistula
      (TEF), is commonly associated with gastroesophageal reflux (GER) after surgical
      repair. One risk factor for anastomotic stricture is post-operative GER. This
      survey assessed practice patterns among attendees at the Canadian Association of
      Pediatric Surgeons (CAPS) annual meeting with respect to management of GER post
      EA-TEF repair. METHODS: A pre-piloted survey was handed out and collected at the
      2012 CAPS annual meeting. Data were entered and coded, and descriptive statistics
      were calculated. RESULTS: We distributed 70 surveys, and 57 (81.4%) surveys were
      returned. On average, the incidence of EA-TEF is 8-10 cases per institution, per
      year. Anti-reflux medication is started immediately post-operatively in 74% of
      patients at institution of feeds (11%), or if symptoms of reflux develop (14%).
      Proton pump inhibitors and H2-receptor antagonists are used in approximately
      equal proportion. Patients are typically kept on anti-reflux medication for 3-6
      months (37%) or 6-12 months (35%). CONCLUSIONS: Most CAPS attendees treat
      postoperative GER prophylactically. However, there is no consistency in
      management strategy regarding which anti-reflux agent to use or for how long. A
      multi-centered study is required to establish a standardized protocol for the
      post-operative management of EA-TEF to prevent reflux and its effect on
      anastomotic strictures.

PMID- 24851755
TI  - Practice variation in gastroschisis: factors influencing closure technique.
AB  - BACKGROUND: Little is known about the factors influencing surgical practice
      variation in newborns with gastroschisis. The purpose of this study was to
      correlate prognostic variables with the intended and actual abdominal closure
      technique and assess related outcomes. METHODS: GS cases were abstracted from a
      national database. Variables evaluated included GA, BW, bowel injury severity
      (GPS), neonatal illness severity (SNAP-II), inborn status, center volume and
      training status, and admission time. Evaluated outcomes by closure method
      included duration of TPN, LOS, and complications. Descriptive, univariate and
      multivariable regression analyses were conducted. RESULTS: The cohort consisted
      of 679 patients. A total of 372 (55%) underwent attempted PR, of which 300 (81%)
      were successful, while 307 (45%) had a silo placed intentionally. Patients
      undergoing attempted PR were more likely to be inborn, have daytime admissions,
      and higher SNAP-II scores. Successful PR was predicted by low risk GPS and high
      volume center. With the exception of higher rates of SSI in the planned silo
      group, outcomes in the successful PR and planned silo groups were comparable.
      CONCLUSION: Practice variation related to type of closure is predicted by
      situational and institutional factors (outborn, nighttime admission, and center
      volume), while outcome variation is attributable to patient factors rather than
      practice variation.

PMID- 24851756
TI  - Human milk fortifier: an occult cause of bowel obstruction in extremely premature
      neonates.
AB  - BACKGROUND: Human milk fortifier (HMF) is used in neonatal units throughout North
      America to facilitate growth of preterm infants. Little data is available on the
      gastrointestinal side effects and potential adverse events. The purpose of this
      paper was to present a series of infants presenting with bowel obstruction
      associated with HMF. METHODS: Cases of HMF obstruction were collected between
      January 2010 and December 2012. Charts were reviewed and relevant data was
      collected. RESULTS: During the study period, 7 premature infants presented with
      bowel obstruction secondary to intestinal concretions of HMF. All babies were
      premature with gestational ages from 25 to 27 weeks. Birth weight was less than
      1000 grams in all patients. Patients presented with feeding intolerance, bilious
      aspirates, abdominal distension, and obstipation. Four of the patients presented
      with acute deterioration and required urgent surgical intervention. CONCLUSIONS:
      HMF is an important source of nutritional support in infants, which is felt to be
      safe. We present a series of infants where its use has resulted in significant
      complications. HMF should be used with caution in infants, especially those with
      a history of necrotizing enterocolitis. Further research should examine the
      calcium, protein, and fatty acid concentration tolerable in the gastrointestinal
      tract of infants.

PMID- 24851757
TI  - Intrauterine growth restriction and prematurity influence regulatory T cell
      development in newborns.
AB  - PURPOSE: The aim of this study was to determine the relationship of birth weight
      and gestational age with regulatory T cells (Tregs) in cord blood of human
      newborns. METHODS: Cord blood mononuclear cells (CBMCs) of 210 newborns were
      analyzed using flow cytometry to identify Tregs (CD3(+), CD4(+), CD25(high),
      FoxP3(high)) and measure FoxP3 mean fluorescence intensity (MFI). Suppressive
      index (SI) was calculated as FoxP3 MFI per Treg. RESULTS: Mode of delivery had no
      significant effect on Tregs at birth. Term babies with growth restriction had
      fewer Tregs than their appropriate weight counterparts but equivalent SI. Preterm
      babies had higher percentages of Tregs, but lower SI than term controls. SI
      steadily increased through gestation. CONCLUSIONS: Intrauterine growth
      restriction is correlated with fewer circulating Tregs and prematurity with
      decreased functionality of Tregs compared to term appropriate weight infants.
      This may have implications in diseases such as necrotizing enterocolitis that
      disproportionately affect premature and lower birth weight infants.

PMID- 24851758
TI  - Inter-rater agreement in the evaluation of abdominal radiographs for necrotizing
      enterocolitis.
AB  - PURPOSE: Abdominal radiographs are frequently employed in the surveillance of
      patients with necrotizing enterocolitis (NEC), with typical findings well
      described. Clinicians interpret and act upon these films at different intervals,
      however, and inter-rater agreement has not been evaluated to date. METHODS:
      Thirty abdominal radiographs of premature infants were distributed to attending
      radiologists (4), pediatric surgeons (4), and trainees (4), who evaluated for
      findings of NEC from a list of eight potential choices (1=normal, 8=perforation).
      Fleiss's Kappa (FK) was used to evaluate concordance between multiple raters with
      0-0.2=slight association and 0.8-1=almost perfect agreement. RESULTS: Practicing
      surgeons had an FK of 0.77 overall (95% CI: 0.67-0.87), but demonstrated poor
      agreement when evaluating decubitus films (FK: 0.39, 95% CI:0.12-0.65).
      Radiologists had excellent inter-rater agreement (FK: 0.81, 95% CI: 0.74-0.88),
      but had only modest agreement with surgeons (FK: 0.59, 95% CI: 0.56-0.63) and
      poor agreement for decubitus films (FK: 0.15, 95% CI: 0.47-0.26). Surgical and
      radiology trainees had fair agreement with their respective attendings (0.60, 95%
      CI: 0.55-0.65 and 0.64, 95% CI: 0.60-0.69, respectively). CONCLUSIONS: While
      inter-rater agreement was good-excellent among attending staff, it was only
      moderate between radiologists and surgeons and between trainees and their
      attendings. This highlights the importance of inter-disciplinary and hierarchical
      communication to optimize clinical decision-making. Decubitus films may be of
      limited value in evaluating patients with NEC.

PMID- 24851759
TI  - Evaluation of sodium deficit in infants undergoing intestinal surgery.
AB  - BACKGROUND: Sodium is a critical growth factor for children. Severe deficits
      cause growth impairment and cognitive dysfunction. Both the diagnosis and risk of
      sodium depletion in children undergoing intestinal surgery are poorly understood.
      METHODS: With IRB approval, children undergoing intestinal surgery (2009-2012)
      who had a urine sodium measurement were retrospectively reviewed. Sodium deficits
      were defined: urine sodium <30 mmol/L and <10 mmol/L were deficient and severely
      deficient, respectively. Demographics, weight changes, and intake (sodium, fluid,
      and nutritional) were tabulated. Data were analyzed using regression analysis and
      Mann Whitney U tests. RESULTS: Thirty-nine patients, 51.3% female, with a
      gestational age of 32.2 weeks and weight of 1.43 kg were identified. The most
      common diagnoses were NEC (38.5%), intestinal atresia (20.5%), and isolated
      perforation (10.3%). Sodium deficiency was documented in 36/39 (92%) and 92.9%
      for those in continuity. Severe deficiency occurred in 64%. Urine sodium was
      significantly correlated with weight gain (p=0.002). Weight gain in patients with
      urine sodium <30 mmol/L was significantly decreased vs. those >=30 mmol/L (+0.58
      g/d vs. +21.6 g/d, p=0.016). CONCLUSION: In this population, sodium depletion is
      common in children undergoing intestinal surgery, even when the colon is in
      continuity. Correction of the sodium deficit to achieve urine sodium >30 mmol/L
      is associated with improved weight gain.

PMID- 24851760
TI  - Citrulline levels following proximal versus distal small bowel resection.
AB  - PURPOSE: Citrulline, a nonprotein amino acid synthesized by enterocytes, is a
      biomarker of bowel length and the capacity to wean from parenteral nutrition.
      However, the potentially variant effect of jejunal versus ileal excision on
      plasma citrulline concentration [CIT] has not been studied. This investigation
      compared serial serum [CIT] and mucosal adaptive potential after proximal versus
      distal small bowel resection. METHODS: Enterally fed Sprague-Dawley rats
      underwent sham operation or 50% small bowel resection, either proximal (PR) or
      distal (DR). [CIT] was measured at operation and weekly for 8 weeks. At necropsy,
      histologic features reflecting bowel adaptation were evaluated. RESULTS: By weeks
      6-7, [CIT] in both resection groups significantly decreased from baseline
      (P<0.05) and was significantly lower than the concentration in sham animals
      (P<0.05). There was no difference in [CIT] between PR and DR at any point. Villus
      height and crypt density were higher in the PR than in the DR group (P<=0.02).
      CONCLUSION: [CIT] effectively differentiates animals undergoing major bowel
      resection from those with preserved intestinal length. The region of intestinal
      resection was not a determinant of [CIT]. The remaining bowel in the PR group
      demonstrated greater adaptive potential histologically. [CIT] is a robust
      biomarker for intestinal length, irrespective of location of small intestine
      lost.

PMID- 24851762
TI  - Comparative outcome analysis of the management of pediatric intussusception with
      or without surgical admission.
AB  - BACKGROUND: Controversy persists about the need to admit patients after
      successful reduction of intussusception. Our hypothesis is that pediatric
      intussusception can be managed with discharge from the emergency department (ED)
      after reduction without increasing morbidity, yielding significant cost savings.
      METHODS: A chart review over 10 years was performed at two Canadian institutions.
      Data abstracted included: demographics, length of stay (LOS), initial and
      recurrence management. Primary outcome was early recurrence and resultant
      management, including LOS and need for operative intervention. Costs were
      calculated using hospital-specific data. RESULTS: 584 patient records were
      assessed: 329 patients were managed with admission after reduction, 239 as
      outpatients. In the admission group, 28 patients had at least one recurrence
      (8.5%), with 8 after discharge. In the outpatient group, 21 patients had at least
      one recurrence (8.8%), with 19 after discharge. The difference post-discharge was
      significant (p=0.004). Outcomes of recurrence did not differ, with 2 patients in
      each group requiring operative intervention. Average LOS in the admission group
      was 90 h, with additional average cost of $1771 per non-operated patient.
      CONCLUSIONS: Pediatric intussusception can be safely managed as an outpatient
      with reliable follow up. Discharge from the ED reduces hospital charges without
      increasing morbidity. This approach should be considered in managing patients
      with intussusception.

PMID- 24851761
TI  - Gastrointestinal bleeding as a complication of serial transverse enteroplasty.
AB  - PURPOSE: Serial transverse enteroplasty (STEP) lengthens and tapers bowel in
      patients with intestinal failure. Evaluation and treatment of serious late
      gastrointestinal bleeding (GIB) in three STEP patients are described. METHODS:
      Patients participating in an interdisciplinary intestinal rehabilitation program
      were reviewed to identify those who underwent STEP and had GIB requiring
      transfusion. RESULTS: Of 296 patients, 23 underwent STEP, and 3 (13%) had
      subsequent GIB requiring transfusion. Diagnoses were vanishing
      gastroschisis/atresia, malrotation/atresia, and gastroschisis.. STEP was
      performed at ages 3-5 months, using 5-15 stapler-firings with an increase in mean
      bowel length from 39 to 62 cm. GIB was diagnosed 5-30 months post-op and resulted
      in 1-7 transfusions per patient. Endoscopy demonstrated staple-line ulceration in
      two patients and eosinophilic enterocolitis in the third. All were treated with
      enteral antibiotics, sulfasalazine, and luminal steroids. Those with ulcers
      responded to bowel rest, and the patient with eosinophilic enterocolitis
      stabilized with luminal steroids. In all three, hemoglobin levels improved
      despite persistent occult bleeding. CONCLUSIONS: Significant GIB is a potential
      late complication of STEP. Endoscopy identified the underlying source of GIB in
      all three patients. A combination of enteral antibiotics, anti-inflammatory
      medications, and bowel rest was effective in treating post-STEP GIB, without the
      need for additional bowel resection.

PMID- 24851763
TI  - Cystic fibrosis: a surgical matter?
AB  - BACKGROUND: Gastroesophageal reflux disease (GERD) is very common in patients
      with chronic lung diseases. We evaluated the incidence of GERD in young patients
      with cystic fibrosis (CF) and defined the characteristics of gastroesophageal
      reflux episodes analyzed by pH-multichannel intraluminal impedance (pH-MII) and
      esophagogastric scintigraphy. PATIENTS AND METHODS: Since 2010, 31 patients with
      CF underwent pH-MII. Scintigraphy and upper endoscopy were performed in positive
      GERD patients. Forced expiratory volume in 1 second (FEV1%) predicted was
      detected. RESULTS: pH-MII was positive in 17/31 (54.8%) patients (mean age: 12.4
      years; range: 4-17 years). pH monitoring detected an average of 64.6 acid reflux
      events 4.4 episodes >5 minutes in duration. The DeMeester score was 38.5.
      Impedance identified a mean number of reflux episodes of 66 (65.2% acid; 32%
      weakly acidic; 2.8% nonacidic), 28% of which reached the proximal esophagus.
      Esophageal transit and gastric emptying were delayed in 6/13 (46.1%) and in 5/15
      (33.3%) cases, respectively. No differences were found in lung function between
      positive and negative GERD patients (P=0.88). CONCLUSIONS: Pediatric patients
      with CF have a high incidence of GERD with acidic events. These patients should
      be investigated with pH-MII and scintigraphy in order to make an early diagnosis
      and determine the most appropriate follow-up.

PMID- 24851764
TI  - Reducing scheduled phlebotomy in stable pediatric patients with blunt liver or
      spleen injury.
AB  - BACKGROUND/PURPOSE: Although consensus-based guidelines exist for managing
      pediatric liver/spleen injuries, optimal phlebotomy frequency is unknown. We
      hypothesize surgeons order more phlebotomy than necessary and propose a pathway
      with one blood draw, early ambulation and discharge, fewer ICU admissions, and
      physiology-driven interventions. METHODS: Records of 120 children with solid
      organ injury from two hospital registries (2008-2012) were analyzed. We compared
      resource utilization between our current management and management if the
      proposed pathway were in place. Paired t-test was used for statistical analysis.
      RESULTS: Sixty-one patients were included (35 spleen, 22 liver, 4 combined).
      Average age was 11.6 (+/-4.2) years, injury severity score 9 (+/-5), and median
      injury grade 3. 51% of children were admitted to the ICU. Average phlebotomy per
      patient was 5 (+/-2) and length-of-stay 4.3 (+/-1.5) days. Three patients became
      unstable and required transfusion. No patients required operation or
      angioembolization. Our pathway would decrease ICU admissions by 65% (p<0.001),
      blood draws by 70% (p<0.001), and length-of-stay by 37% (p<0.001), while
      identifying all patients requiring transfusion based on hemodynamic status.
      CONCLUSION: Our data suggest that clinical parameters could identify patients
      requiring intervention and decrease resource utilization. This suggests that
      serial phlebotomy may be unnecessary, and the proposed pathway is worthy of
      prospective validation.

PMID- 24851765
TI  - Burden of complications from needle penetration of plastic ports in children.
AB  - BACKGROUND: Complications of totally implanted venous access ports are well
      documented. A concerning mechanical complication we have encountered is posterior
      penetration of plastic ports with the access needle. The purpose of this study is
      to investigate the burden of posterior penetrations. METHODS: We performed a
      retrospective review of all ports placed between November 2007 and December 2011
      at a single institution. RESULTS: There were 247 children who received a port.
      117 children (47%) received a port with a plastic posterior wall, 95 children
      (38%) received a port with a metal posterior wall, and 35 children (14%) had
      ports that were unable to be identified as plastic or metal. Posterior port
      penetrations occurred 8 times (3.2% overall, 6.8% of plastic ports). All
      perforations occurred in plastic ports of a single brand and product code.
      Average time from port insertion to penetration was 11.2+/-21.3 months (range 0.3
      to 63.4 months). Other complications included catheter malfunction (14),
      infection (9), pain (2), inability to draw/aspirate (4), leak (3), port migration
      (2), and malfunctioning not otherwise specified (15). CONCLUSIONS: There is an
      unacceptably high risk of needle penetration of the posterior wall of plastic
      ports. We recommend utilizing ports with metal backing to avoid this
      complication.

PMID- 24851766
TI  - Determinants of wait time for infant inguinal hernia repair in a Canadian
      children's hospital.
AB  - BACKGROUND: Longer wait time for infant inguinal hernia (IH) repair is associated
      with higher complication rates. We wished to determine if socioeconomic and
      demographic factors influence wait times for IH repair. METHODS: Children <2
      years old with IH at a Canadian children's hospital were retrospectively
      reviewed. Days from diagnosis to surgical consultation (W1) and from consultation
      to repair (W2) were collected along with demographic, medical, and socioeconomic
      data. Linear regression analysis was performed. RESULTS: A total of 131 patients
      were appropriate for analysis (82.4% male). Median distance to hospital was 27.5
      km (IQR=10.5-50.4) and median income was $34,477 (IQR=30,127-41,986). Median W1,
      W2, and Wtotal (W1+W2) were 24 (IQR=8-48), 43 (IQR=21-69) and 79 (IQR=38-112)
      days, respectively. Wait times were shorter in infants who were male (p=0.044),
      symptomatic (p<0.001), diagnosed in the ED (p<0.001), or had an incarcerated
      hernia (p=0.006). They were longer for premature infants (p=0.009) and those with
      significant comorbidities (p=0.018). Neither income (p=0.328) nor distance from
      hospital (p=0.292) was associated with longer wait times. CONCLUSION: Wait times
      for IH repair were appropriately influenced by medical risk factors. Income and
      distance to hospital did not appear to influence wait times. A population-based
      study is needed to determine if these findings reflect a general trend within the
      Canadian health care system.

PMID- 24851767
TI  - Undescended testes: does age at orchiopexy affect survival of the testis?
AB  - PURPOSE: The optimal age at which to perform orchiopexy for cryptorchidism has
      long been debated. The aim of this study was to determine if age at orchiopexy
      affected testicular atrophy. METHODS: A retrospective review of patients
      undergoing orchiopexy from 2000 to 2010 was conducted. An individual testis,
      rather than patient, was used as the dependent variable. A total of 349 testicles
      from 1126 charts (ICD-9=752.51) were identified. Primary study outcome was
      testicular survival without atrophy. RESULTS: Mean follow up for the study was 25
      months. There was postoperative atrophy in 27 testes (7.7%). Intraabdominal
      testicle was independently associated with increased postsurgical atrophy
      (p<0.0001). The odds of postsurgical atrophy were 15.66 times higher for an
      abdominal vs. inguinal location (95% CI: 5.5-44.6). Testicular atrophy was
      highest for orchiopexy at ages 13-24 months (n=16 of 133, 12%) vs. those less
      than 13 months (n=3 of 64, 5%), and those greater than 24 months (n=8 of 152, 5%)
      (p=0.0024). After adjusting for location, age was not statistically significant
      with postsurgical atrophy (p=0.055). CONCLUSIONS: From this study we conclude
      that there is no increase in testicular atrophy in patients less than 13 months.

PMID- 24851768
TI  - Transanal pullthrough for Hirschsprung disease: matched case-control comparison
      of Soave and Swenson techniques.
AB  - BACKGROUND: Both the Swenson and the Soave procedures have been adapted to a
      transanal approach. The purpose of this study was to compare outcomes following
      the transanal Swenson and Soave procedures using a matched case control analysis.
      METHODS: A retrospective chart review was performed to identify all transanal
      Soave and Swenson pullthroughs done at 2 tertiary care children's hospitals
      between 2000 and 2010. Patients were matched for gestational age, mean weight at
      time of the operation, level of aganglionosis, and presence of co-morbidities.
      Student's t-test and chi-squared analysis were performed. RESULTS: Fifty-four
      patients (Soave 27, Swenson 27) had adequate data for matching and analysis. Mean
      follow-up was 4+/-1.6 years and 3.2 +/-2.7 years for the Soave and Swenson
      groups, respectively. No significant differences in mean operating time
      (Soave:191+/-55, Swenson:167+/-61 min, p=0.6), overall hospital stay (6+/-4 vs
      7.8+/-5 days, p=0.7), and number with intra-operative complications (3 vs 4,
      p=1.0), post-operative obstructive symptoms (6 vs 9, p=0.5), enterocolitis
      episodes (4 vs 4, p=1.0), or fecal incontinence (0 vs 2, p=0.4) were noted.
      CONCLUSION: After controlling for potential confounders, there were no
      significant differences in the short and intermediate term outcome between
      transanal Soave and transanal Swenson pullthrough procedures.

PMID- 24851769
TI  - Determinants of appendicitis outcomes in Canadian children.
AB  - BACKGROUND: Outcomes of appendicitis may be influenced by access to healthcare.
      We investigated the determinants of pediatric appendicitis outcomes in the single
      payer Canadian healthcare system. METHODS: Children coded for urgent appendectomy
      by the Canadian Institute of Health Information during the period 2004-2010 were
      analyzed. Misdiagnosis rate, perforated appendicitis rate, and hospital stay were
      the outcomes studied. Analyzed variables included age, gender, domicile,
      socioeconomic status, surgeon's specialty, hospital type, region, and operative
      approach. Logistic regression analysis was used to examine associations, and a
      quintile regression model examined the effect on median hospital stay. RESULTS:
      41,702 patients were studied. A higher rate of perforated appendicitis was
      associated with lower age [OR 2.66], male gender [OR 1.18], pediatric surgeon [OR
      1.25], and treatment outside the Maritimes. A higher rate of misdiagnosis was
      associated with lower age [OR 1.53], female gender [OR 2.29], non-children's
      hospital [OR 1.33], and western Canada [OR 1.22]. A significantly longer hospital
      stay was associated with open appendectomy, pediatric surgeon, and the
      Territories for simple appendicitis, and open appendectomy, pediatric surgeon,
      children's hospital, and the Maritimes for perforated appendicitis. CONCLUSIONS:
      In Canada, outcomes of pediatric appendicitis are associated with regional and
      treatment-level factors. Rural domicile and socioeconomic status do not affect
      outcomes.

PMID- 24851770
TI  - Non-operative management of early, acute appendicitis in children: is it safe and
      effective?
AB  - PURPOSE: The purpose of this study was to determine if early, acute appendicitis
      in children can be safely and effectively managed with antibiotics alone.
      METHODS: A retrospective review was performed of children (<18 yrs) treated non
      operatively (NOM) for early, acute appendicitis since May 2012. These were
      compared to patients treated with appendectomy between January 2011 and October
      2011 (OM). Inclusion criteria included: (a) symptoms <48 h, (b) localized
      peritonitis, and (c) ultrasound findings consistent with early, acute
      appendicitis. RESULTS: Twelve patients (66% female, mean age 12.2,SD=4.2 yrs)
      were treated non-operatively, while 12 (50% female, mean age 12.5,SD=3.2 yrs)
      were treated operatively. Two NOM children (16.7%) required initial appendectomy.
      One patient developed recurrent appendicitis requiring appendectomy 7 months post
      discharge. Four other NOM patients returned with symptoms but did not require
      admission or surgery. Two OM patients (8.3%) had hospital visits and admissions
      related to surgical site infections. Mean length of stay (LOS) for the first
      visit was 1.5 days (SD=1.0d) (NOM) vs. 1.3 days (SD=0.5d) (OM) (p=0.61).
      Including first and subsequent admissions, mean LOS was 1.8 days (SD=1.1d) (NOM)
      vs. 1.7 days (SD=1.5d) (OM) (p=0.97). CONCLUSION: Early acute appendicitis in
      appropriately selected children can be successfully treated non-operatively.
      Randomized trials with longer follow-up are required.

PMID- 24851771
TI  - Pediatric surgical camps as one model of global surgical partnership: a way
      forward.
AB  - BACKGROUND/PURPOSE: A uniquely Ugandan method of holding surgical "camps" has
      been one means to deal with the volume of patients needing surgery and provides
      opportunities for global partnership. METHODS: We describe an evolved partnership
      between pediatric surgeons in Uganda and Canada wherein Pediatric Surgical Camps
      were organized by the Ugandans with team participation from Canadians. The camp
      goals were to provide pediatric surgical and anesthetic service and education and
      to foster collaboration as a way forward to assist Ugandan health delivery.
      RESULTS: Three camps were held in Uganda in 2008, 2011, and 2013. A total of 677
      children were served through a range of operations from hernia repair to more
      complex surgery. The educational mandate was achieved through the involvement of
      10 Canadian trainees, 20 Ugandan trainees in surgery and anesthesia, and numerous
      medical students. Formal educational sessions were held. The collaborative
      mandate was manifest in relationship building, an understanding of Ugandan health
      care, research projects completed, agreement on future camps, and a proposal for
      a Canadian-Ugandan pediatric surgery teaching alliance. CONCLUSION: Pediatric
      Surgical Camps founded on global partnerships with goals of service, education,
      and collaboration can be one way forward to improve pediatric surgery access and
      expertise globally.

PMID- 24851772
TI  - Motion analysis in the pediatric laparoscopic surgery (PLS) simulator: validation
      and potential use in teaching and assessing surgical skills.
AB  - BACKGROUND: Construct validity for the pediatric laparoscopic surgery (PLS)
      simulator has been established through a scoring system based on time and
      precision. We describe the development and initial validation of motion analysis
      to teach and assess skills related to pediatric minimal access surgery (MAS).
      METHODS: Participants were asked to perform a standardized intracorporeal
      suturing task. They were classified as novices, intermediates, and experts.
      Motion in the four degrees of freedom available during traditional MAS (PITCH,
      YAW, ROLL and SURGE) was assessed using range, velocity, and acceleration.
      RESULTS: Analysis of motion allowed discrimination between the 75 participants
      according to level of expertise. The most discriminating motion parameter was the
      acceleration in performing the ROLL (pronation/supination) with values of 30+/-27
      for novices, 15+/-5 for intermediates, and 3.7+/-3 for experts (p<0.001).
      CONCLUSIONS: Tracking and analyzing the motion of instruments within the PLS
      simulator allow discrimination between novices, intermediates, and experts, thus
      establishing construct validity. Further development may establish motion
      analysis as a useful "real time" modality to teach and assess MAS skills.

PMID- 24851773
TI  - Informed consent for emergency surgery--how much do parents truly remember?
AB  - BACKGROUND/PURPOSE: The purpose of this study was to evaluate parental retention
      of possible surgical complications in children undergoing emergency laparoscopic
      appendectomy. METHODS: A prospective pilot study involving parents whose children
      had emergency laparoscopic appendectomy was performed. Parents were counseled
      regarding 7 potential complications of laparoscopic appendectomy. They were asked
      to recall this list immediately after the consent process (immediate recall, IR)
      and before discharge from inpatient stay (delayed recall, DR). A score (0-7) was
      awarded indicating the number of correct answers. For each recall, parents were
      also reminded on complications they omitted (prompted recall). One surgeon
      administered all consents in person. Demographic data were collected. Data were
      reported as median (range). RESULTS: Twenty-one mothers and 10 fathers were
      recruited, aged 42 years (30-54). Nine (29%) had university or post-graduate
      education. Score for IR was 2 (0-6). Five (16%) parents scored 0. Upon prompting
      after IR, 20 (65%) parents had no impression of at least 1 complication. Score
      for DR was 2 (0-7), while 7 (23%) parents scored 0. At prompting after DR, 25
      (81%) had no memory of at least one complication. Eight (26%) demonstrated
      improved DR scores. Scores were not affected by patient demographics or time
      between interviews. CONCLUSIONS: There is poor parental retention of information
      provided during operative consent. Hence, proper documentation of this process is
      essential.

PMID- 24851774
TI  - Epidural analgesia versus intravenous patient-controlled analgesia following
      minimally invasive pectus excavatum repair: a systematic review and meta
      analysis.
AB  - BACKGROUND/PURPOSE: The minimally invasive pectus excavatum repair (MIPER) is a
      painful procedure. The ideal approach to postoperative analgesia is debated. We
      performed a systematic review and meta-analysis to assess the efficacy and safety
      of epidural analgesia compared to intravenous Patient Controlled Analgesia (PCA)
      following MIPER. METHODS: We searched MEDLINE (1946-2012) and the Cochrane
      Library (inception-2012) for randomized controlled trials (RCT) and cohort
      studies comparing epidural analgesia to PCA for postoperative pain management in
      children following MIPER. We calculated weighted mean differences (WMD) for
      numeric pain scores and summarized secondary outcomes qualitatively. RESULTS: Of
      699 studies, 3 RCTs and 3 retrospective cohorts met inclusion criteria. Compared
      to PCA, mean pain scores were modestly lower with epidural immediately (WMD 
      1.04, 95% CI -2.11 to 0.03, p=0.06), 12 hours (WMD -1.12; 95% CI -1.61 to -0.62,
      p<0.001), 24 hours (WMD -0.51, 95%CI -1.05 to 0.02, p=0.06), and 48 hours (WMD 
      0.85, 95% CI -1.62 to -0.07, p=0.03) after surgery. We found no statistically
      significant differences between secondary outcomes. CONCLUSIONS: Epidural
      analgesia may provide superior pain control but was comparable with PCA for
      secondary outcomes. Better designed studies are needed. Currently the analgesic
      technique should be based on patient preference and institutional resources.

PMID- 24851775
TI  - Surgical and anesthetic considerations in histrelin capsule implantation for the
      treatment of precocious puberty.
AB  - BACKGROUND: Precocious puberty treatment traditionally meant anxiety-provoking
      monthly depot injections until the advent of the annually implanted histrelin
      capsule. This study is the first to evaluate the surgical and anesthetic aspects
      of histrelin implantation for precocious puberty. METHODS: All cases from one
      surgeon at a tertiary pediatric hospital were reviewed for patient age,
      anesthetic type, technical difficulties, and complications. RESULTS: From 12/2007
      to 3/2013, 114 cases (49% implantations, 25% removals/re-implantations, 25%
      removals) were performed. Local anesthesia was employed in 100% of non-general
      anesthesia cases (n=109, 96%), augmented by inhaled N2O in 49%. Five patients
      (4%) underwent general anesthesia: three neurologically-impaired and two
      coordinated with scheduled MRIs. Procedural difficulties (n=18, 16%) included
      implant fracture during removal (n=16/58 removals, 28%). Fracture never occurred
      during implantation. Three children (3%) suffered complications. One infection
      was treated with antibiotics, and two implants were removed for systemic allergic
      reaction. Six children (5%) had unscheduled post-operative checks for pain (n=3,
      3%), allergy to elastic dressing (n=2, 2%), or rash (n=1, 1%). Mean charges for
      general anesthesia were $10,188+/-1292 versus $528+/-147 for N2O or local alone
      (p<0.0001). CONCLUSION: While histrelin implantation is straightforward, removal
      presents technical challenges. Local anesthesia, with possible N2O
      supplementation, is well-tolerated and introduces substantial resource and cost
      savings.

PMID- 24851776
TI  - A pilot investigation of a Pediatric Surgery Journal Club.
AB  - BACKGROUND: The CanMEDS competency "scholar" encompasses the creation,
      dissemination, application, and translation of medical knowledge. We hypothesize
      that a structured journal club (JC) for pediatric surgical trainees would meet
      these objectives in an enjoyable and long-lasting manner. METHODS: A JC involving
      two pediatric surgery training programs was created with each session focusing on
      a specific study design. Pre-tests/post-tests were administered before/after each
      session with durability of learning assessed during the following session.
      Metrics analyzed included participant satisfaction and an appraisal of evidence
      based medicine (EBM) principals. Test results were analyzed using the paired T
      test with p<0.05 considered significant. RESULTS: On average, 14 participants
      attended each session, with all trainees present (4). While participants believed
      they understood EBM principles, 40% were unfamiliar with question formulation,
      48% were unfamiliar with critical appraisal tools, and 60% had not appraised an
      article within the previous year. Pre-test to post-test comparison yielded an
      improvement in mean score (20=perfect score): 10.8 to 16.9, p<0.01. Measures of
      participant satisfaction were uniformly positive. CONCLUSION: A structured
      Pediatric Surgery Journal Club addresses scholarly training objectives in a
      highly satisfactory manner and yields durable learning. A web-based curriculum
      based on this model could serve as an important educational tool for trainees and
      attending staff alike.

PMID- 24851779
TI  - Review of nutritional assessment and clinical outcomes in pediatric surgical
      patients: does preoperative nutritional assessment impact clinical outcomes?
AB  - INTRODUCTION: Malnourished adult patients who undergo surgical procedures tend to
      have worse clinical outcomes compared to well-nourished patients. In the
      pediatric surgical patient, nutritional assessment is considered a critical
      aspect of the initial evaluation, but a correlation between preoperative
      malnutrition and poor surgical outcomes is not clear. We hypothesized that an
      evidence-based review would reveal that measures of nutritional assessment in
      children would not correlate pre-operative malnutrition with poor surgical
      outcomes. MATERIALS AND METHODS: A search of major English language medical
      databases (Medline, Cochrane, SCOPUS) was conducted for the key words nutritional
      assessment, pediatric, children, surgery, and outcomes. All methods of
      nutritional assessment in pediatric surgery were evaluated for their relevance
      and relation to outcomes after surgery. The Oxford Center for Evidence Based
      Medicine (CEBM) classification for levels of evidence was used to develop grades
      of clinical recommendation for each variable studied. RESULTS: 35 articles were
      evaluated after an exhaustive literature search, of which six met inclusion
      criteria for this review. There is a paucity of high quality evidence correlating
      preoperative malnutrition in pediatric surgical patients with clinical outcomes.
      Factors contributing to the low level of evidence include a lack of high quality
      randomized controlled trials, a lack of consensus in study design and methods,
      and utilization of incongruous methods of nutritional assessment, including
      methods that may be unproven in the study population. CONCLUSION: Larger multi
      center randomized studies are needed to offer higher level of evidence to support
      nutritional intervention prior to major elective pediatric surgery.

PMID- 24851778
TI  - Optimizing resources for the surgical care of children: an American Pediatric
      Surgical Association Outcomes and Clinical Trials Committee consensus statement.
AB  - The United States' healthcare system is facing unprecedented pressures: the
      healthcare cost curve is not sustainable while the bar of standards and
      expectations for the quality of care continues to rise. Systems committed to the
      surgical treatment of children will likely require changes and reorganization.
      Regardless of these mounting pressures, hospitals must remain focused on
      providing the best possible care to each child at every encounter. Available
      clinical expertise and hospital resources should be optimized to match the
      complexity of the treated condition. Although precise criteria are lacking, there
      is a growing consensus that the optimal combination of clinical experience and
      hospital resources must be defined, and efforts toward this goal have been
      supported by the Regents of the American College of Surgeons, the members of the
      American Pediatric Surgical Association, and the Society for Pediatric Anesthesia
      (SPA) Board of Directors. The topic of optimizing outcomes and the discussion of
      the concepts involved have unfortunately become divisive. Our goals, therefore,
      are 1) to provide a review of the literature that can provide context for the
      discussion of regionalization, volume, and optimal resources and promote mutual
      understanding of these important terms, 2) to review the evidence that has been
      published to date in pediatric surgery associated with regionalization, volume,
      and resource, 3) to focus on a specific resource (anesthesia), and the
      association that this may have with outcomes, and 4) to provide a framework for
      future research and policy efforts. 

PMID- 24851780
TI  - Transanal rectal mucosectomy and partial internal anal sphincterectomy for
      Hirschsprung's disease.
AB  - PURPOSE: Hirschsprung-associated enterocolitis (HAEC) is a serious complication
      of Hirschsprung's disease (HD), with generalized sepsis and high mortality rate.
      Although the surgical correction of HD is mostly successful, challenges remain in
      the management of children with repeated episodes of enterocolitis. The authors
      describe a novel modification of transanal rectal mucosectomy and partial
      internal anal sphincterectomy (TRM-PIAS) for HD. METHODS: One hundred twenty
      seven HD children aged from 8 days to 16 years who successfully underwent TRM
      PIAS were reviewed. TRM-PIAS was carried out circumferentially along the
      anorectal line. Anterior dissection was conducted between the rectal submuscosal
      layer and the rectal muscular sleeve. The posterior dissection was performed
      along the plane between internal and external anal sphincters. Normal colon was
      pulled through and anastomosed to anal mucosa. Aganglionic segment, rectal
      mucosa, part of internal anal sphincter and posterior rectal muscular cuff were
      removed. Twenty-five age-matched children without defecation dysfunction were
      used as the control group in the study of anal resting pressure. RESULTS:
      Patients were followed up for 6-12 years (median: 8.2 years). The median age at
      last follow-up was 12.2 years (7.2-20.1 years). The incidence of enterocolitis
      decreased from 33.9% (43/127) preoperatively to 1.6% (2/127) postoperatively
      (P<0.01). The incidence of constipation decreased from 100% (127/127)
      preoperatively to 2.4% (3/127) postoperatively (P<0.01). Soiling rate on
      postoperative 1 month was 32.3%. It gradually decreased to 1.6% 6 months later.
      Anorectal manometries showed that mean anal resting pressure was significantly
      reduced from 37.9+/-12.5 mm Hg preoperatively to 20.2+/-6.4 mm Hg on
      postoperative 1 month and 24.8+/-9.9 mm Hg on postoperative 6 months, which were
      similar to age-matched normal controls (27.9+/-9.6 mm Hg, P>0.05). CONCLUSIONS:
      TRM-PIAS is effective in treatment of HD. It is associated with low postoperative
      HD-associated enterocolitis.

PMID- 24851781
TI  - Congenital urethral polyps in children: report of 18 patients and review of
      literature.
AB  - BACKGROUND/PURPOSE: To evaluate the presentation, diagnosis and management of
      congenital urethral polyps (CUP) in children and to report the results of the
      endoscopic resection of polyp with long-term follow-up. METHODS: Between April
      1995 to March 2010, 18 children (14 boys, 4 girls) with CUP were treated. The
      most common presentation was urinary outflow obstruction/retention, hematuria or
      protruding polyp from the urethra meatus in girls. Six patients presented with
      vesicoureteral reflux (VUR). All children (except one) underwent a transurethral
      resection of the CUP. RESULTS: Following the endoscopic resection of the polyps,
      there was no polyp recurrence, and all patients became symptom-free. The children
      exhibited no reflux, urinary retention, hematuria or urinary tract infection
      (UTI) following endoscopic management. Abnormal uroflowmetry patterns returned to
      normal following the resection of the polyp for one year after the operation.
      CONCLUSIONS: Urethral polyps must be considered in every child with history of
      triad of recurrent intermittent urinary retention, hematuria and lower urinary
      tract symptoms. The cure can be achieved in all cases by an endoscopic approach.
      This type of tumor is always benign and very rarely recurs, unless the pedicle
      stalk is not resected. The endoscopic management of reflux is unnecessary in this
      group of patients due to their natural history of secondary reflux.

PMID- 24851782
TI  - Pitfalls abound when using administrative health databases.

PMID- 24851783
TI  - Reply to letter to the editor.

PMID- 24851785
TI  - The fate of osteophytes in the superolateral region of the acetabulum after total
      hip arthroplasty.
AB  - Acetabular osteophytes are common during total hip arthroplasty (THA). However,
      the fate and role of superolateral osteophytes of the acetabulum after THA remain
      unclear. The present study reviewed a series of radiographic changes in the
      osteophytes on the superolateral region of the acetabulum in 35 hips. The mean
      follow-up period was 42.2months. The results revealed that the osteophytes that
      were not in contact with the superolateral edge of acetabular cup were gradually
      absorbed after THA. In contrast, the osteophytes that were in contact with the
      superolateral edge of the acetabular cup underwent remodeling, formed regular
      trabecula, were stress bearing, and eventually integrated with the acetabular cup
      and the original acetabular bone, and should play a role in stabilizing the
      acetabular cup.

PMID- 24851784
TI  - Clinical presentation and outcome of 20 fetuses with parvovirus B19 infection
      complicated by severe anemia and/or fetal hydrops.
AB  - AIM: The aim of this study was to assess the prognosis of parvovirus B19
      infection with severely anemic and/or hydropic fetuses according to initial
      ultrasound and biological criteria. MATERIAL AND METHODS: Retrospective study of
      20 cases of congenital parvovirus B19-proven infection (positive PCR) complicated
      by fetal anemia and/or hydrops was examined. Anemia was suspected on an elevated
      peak systolic velocity of the middle cerebral artery and was confirmed by fetal
      blood sampling. RESULTS: Survival rate was 70% (14/20) overall and 76% (13/17)
      for fetuses with one or more transfusions. When fetal effusion regressed after
      the transfusion, all 11 fetuses survived, and neonatal condition was favorable
      for all. Among the 14 live-born children, there was one neonatal death and one
      admission to the neonatal care unit with no major complications. CONCLUSION:
      Despite active management by transfusion in fetuses with parvovirus B19
      infection, mortality remained substantial during the acute phase of anemia and
      fetal hydrops. Regression of effusion appears to be an important variable for
      prognosis. Non-anemic forms exist with isolated refractory ascites or pleural
      effusion. Maternal mirror syndrome appears to reflect the intensity and
      persistence of the fetal anemia.

PMID- 24851786
TI  - Dental clearance prior to elective arthroplasty may not be needed for everyone.
AB  - We investigated the prevalence and risk factors for preoperative dental clearance
      failure in joint arthroplasty patients. Over a 5-month period, all patients
      scheduling total joint arthroplasty completed a dental questionnaire. Data
      collected included demographics, medical and dental history, dental hygiene
      practices, frequency of dental care, and results of dental clearance. Of the 300
      patients, 35 (12%) failed dental clearance. Risk factors included tobacco use,
      poor flossing habits, history of tooth extraction, age, narcotic use, and lack of
      a dentist visit within 12 months. Of 189 patients who lacked the 3 least
      prevalent risk factors (tobacco use, narcotic use, no dental visit within 12
      months), 11 (6%) failed dental clearance. Selective dental clearance based on
      patient risk stratification may be a reasonable approach.

PMID- 24851787
TI  - Cementless bipolar hemiarthroplasty using a micro-arc oxidation coated stem in
      patients with displaced femoral neck fractures.
AB  - Femoral stem fixation for displaced femoral neck fractures in osteoporotic
      patients is an ongoing debate. We evaluated the outcome of 136 cementless bipolar
      hemiarthroplasty using a Micro-arc oxidation (MAO) coated stem. All patients
      survived the procedure and were discharged from the hospital. Thirty- and 90-day
      mortality rates were 0.7% and 2.2%, respectively. Ninety-eight hips were followed
      for a minimum of 2years (mean, 44months) postoperatively. Three stems were
      revised because of a periprosthetic fracture. Although cortical stress shielding
      around the stem was observed in 3 hips, there was no loosening or osteolysis.
      Cementless bipolar hemiarthroplasty using a MAO-coated stem is a useful and safe
      option to treat displaced femoral neck fractures.

PMID- 24851788
TI  - Acute delayed infection: increased risk in failed metal on metal total hip
      arthroplasty.
AB  - Adverse local tissue reactions occurring in metal-on-metal total hip arthroplasty
      (MoM THA) could potentially lead to secondary failure modes such as dislocation
      or infection. The authors report a series of 124 patients treated with MoM hip
      arthroplasty between 2006 and 2010 with a minimum follow-up of 3 years. Eight
      hips presented with acute delayed or late periprosthetic joint infection (PJI)
      (defined as an infection occurring after 3 months in an otherwise well
      functioning implant). The rate of infection observed was higher than expected,
      almost 4 times higher (5.6%) compared to previous historical cohorts from our
      institution (1.3%). This high risk of infection in patients with DePuy ASR
      implants requires further study but we theorize that the increased prevalence of
      infection could be due to a combination of particulate debris, molecular (rather
      than particulate) effects of Co and Cr ions on soft tissues, and/or products of
      corrosion that may change the local environment predisposing to infection.

PMID- 24851789
TI  - Modeling polyethylene wear acceleration due to femoral head dislocation damage.
AB  - Scratching, scraping, and metal transfer to femoral heads commonly accompany
      acetabular shell contact during dislocation and closed reduction maneuvers. While
      head damage conceptually leads to accelerated wear, reports on this subject are
      mainly anecdotal, and differ widely on the potency of such effect. Towards better
      understanding this relationship, a physically validated finite element (FE) model
      was used to compute polyethylene wear acceleration propensity of specific head
      damage patterns on thirteen retrievals. These FE models estimated wear increases
      averaging half an order of magnitude when compared to simulations for undamaged
      heads. There was no correlation between the number of dislocations sustained and
      wear acceleration. These results underscore the importance of implant-gentle
      closed reduction, and heightened wear monitoring of successfully reduced
      dislocation patients. 

PMID- 24851790
TI  - Management of periprosthetic joint infection after total hip arthroplasty using a
      custom made articulating spacer (CUMARS); the Exeter experience.
AB  - Periprosthetic joint infection (PJI) after THA is a major complication with an
      incidence of 1%-3%. We report our experiences with a technique using a custom
      made articulating spacer (CUMARS) at the first of two-stage treatment for PJI.
      This technique uses widely available all-polyethylene acetabular components and
      the Exeter Universal stem, fixed using antibiotic loaded acrylic cement. Seventy
      six hips were treated for PJI using this technique. Performed as the first of a
      two-stage procedure, good functional results were commonly seen, leading to
      postponing second stage indefinitely with retention of the CUMARS prosthesis in
      34 patients. The CUMARS technique presents an alternative to conventional
      spacers, using readily available components that are well tolerated, allowing
      weight bearing and mobility, and achieving comparable eradication rates. 

PMID- 24851791
TI  - An increase in cranial acetabular version with age: implications for
      femoroacetabular impingement.
AB  - This cadaveric study aimed to determine if acetabular retroversion demonstrates
      predictable changes with age that could inform understanding of factors that may
      contribute to the pathophysiology of femoroacetabular impingement. Two-hundred
      forty pelves were divided into young and old groups. Version was measured at the
      cranial (5mm below superior rim), central (transverse of acetabulum), and caudal
      (5mm above inferior rim) locations. The data showed a significant difference
      between young (10+/-10 degrees ) and old (13+/-9 degrees ) cranial version
      (P=.02). Cranial retroversion increases with age and may reflect a developmental
      component in the etiology of the focal rim impingement lesion or ossification of
      the damaged labrum. Global acetabular retroversion does not appear to change with
      age and may reflect a congenital etiology. 

PMID- 24851792
TI  - Robotic guidance does not improve component position or short-term outcome in
      medial unicompartmental knee arthroplasty.
AB  - We performed a retrospective review in a matched group of patients on the use of
      robotic-assisted UKA implantation versus UKA performed using standard operative
      techniques to assess differences between procedures. While both techniques
      resulted in reproducible and excellent outcomes with low complication rates, the
      results demonstrate little to no clinical or radiographic difference in outcomes
      between cohorts. Average operative time differed significantly with, and average
      of 20 minutes greater in, the robotic-assisted UKA group (P=0.010). Our minimal
      clinical and radiographic differences lend to the argument that it is difficult
      to justify the routine use of expensive robotic techniques for standard medial
      UKA surgery, especially in a well-trained, high-volume surgeon. Further surgical,
      clinical and economical study of this technology is necessary.

PMID- 24851793
TI  - The effect of a single dose of preemptive pregabalin administered with COX-2
      inhibitor: a trial in total knee arthroplasty.
AB  - We sought to compare a group (Group L) (n=21) of patients that underwent total
      knee arthroplasty and received a single preoperative dose of pregabalin combined
      with a COX-2 inhibitor with a control group (Group C) (n=20) that only received a
      COX-2 inhibitor in terms of (1) acute postoperative pain intensity, (2) analgesic
      consumption, and (3) functional recovery. Mean cumulative fentanyl consumption
      during the first 48 hours was lower in Group L than in Group C (P<0.05). The pain
      scores at rest were lower in Group L at 6 and 12 hours after surgery (P<0.05). No
      significant intergroup difference was noted in functional recovery. The addition
      of pregabalin led to an additive reduction in early postoperative pain and
      analgesic consumption.

PMID- 24851794
TI  - Intraoperative platelet-rich plasma does not improve outcomes of total knee
      arthroplasty.
AB  - This randomized controlled study was conducted to assess the effects of platelet
      rich plasma (PRP) on outcomes of total knee arthroplasty (TKA). Forty patients
      who underwent unilateral TKA were evaluated prospectively; 20 received
      intraoperative PRP and 20 served as control subjects. The results showed no
      significant differences in reduction of bleeding, range of motion, swelling
      around the knee joint, muscle power recovery, pain, Knee Society Scores, and Knee
      Injury and Osteoarthritis Outcome Score between the 2 groups. Additionally, no
      distinct clinical characteristics were found in patients who received
      intraoperative PRP. Therefore, we conclude that intraoperative PRP does not
      improve outcomes of TKA. 

PMID- 24851795
TI  - Impact of metabolic syndrome on perioperative complication rates after total
      joint arthroplasty surgery.
AB  - This study investigated the impact of metabolic syndrome (MetS) on perioperative
      and postoperative complication rates: the results of a cohort of 168 total hip
      and knee arthroplasties, 63 of normal weight, 105 with obesity without risk
      factors for metabolic syndrome and 39 with obesity and other factors that
      classify them with metabolic syndrome. Patients with metabolic syndrome were more
      likely to have complications than those without metabolic syndrome (P=0.0156).
      Perioperative and postoperative complication rates for the MetS and control
      groups were 35.9% and 16.3%, respectively. Elevated BMI was the element of MetS
      that had the largest impact on post-surgical complication rates, and this was
      statistically significant (P=0.0028). The presence of MetS in patients undergoing
      total joint arthroplasty has a significant impact on surgical complication rates.
      This cannot be attributed to the BMI component alone, and may help guide efforts
      of patient optimization prior to total joint arthroplasty. 

PMID- 24851796
TI  - Treatment patterns among colorectal cancer patients in South Australia: a
      demonstration of the utility of population-based data linkage.
AB  - RATIONALE, AIMS AND OBJECTIVES: Population level data on colorectal cancer (CRC)
      management in Australia are lacking. This study assessed broad level patterns of
      care and concordance with guidelines for CRC management at the population level
      using linked administrative data from both the private and public health sectors
      across South Australia. Disparities in CRC treatment were also explored. METHOD:
      Linking information from the South Australian Cancer Registry, hospital
      separations, radiotherapy services and hospital-based cancer registry systems
      provided data on the socio-demographic, clinical and treatment characteristics
      for 4641 CRC patients, aged 50-79 years, diagnosed from 2003 to 2008. Factors
      associated with receiving site/stage-specific treatments (surgery, chemotherapy
      and radiotherapy) and overall concordance with treatment guidelines were
      identified using Poisson regression analysis. RESULTS: About 83% of colon and 56%
      of rectal cancer patients received recommended treatment. Provision of neo
      adjuvant/adjuvant therapies may be less than optimal. Radiotherapy was less
      likely among older patients (prevalence ratio 0.7, 95% confidence interval 0.5
      0.8). Chemotherapy was less likely among older patients (0.7, 0.6-0.8), those
      with severe or multiple co-morbidities (0.8, 0.7-0.9), and those from rural areas
      (0.9, 0.8-1.0). Overall discordance with treatment guidelines was more likely
      among rectal cancer patients (3.0, 2.7-3.3), older patients (1.6, 1.4-1.8), those
      with multiple co-morbid conditions (1.3, 1.1-1.4), and those living in rural
      areas (1.2, 1.0-1.3). CONCLUSIONS: Greater emphasis should be given to ensure CRC
      patients who may benefit from neo-adjuvant/adjuvant therapies have access to
      these treatments.

PMID- 24851797
TI  - Three-dimensional extracellular matrix scaffolds by microfluidic fabrication for
      long-term spontaneously contracted cardiomyocyte culture.
AB  - To repair damaged cardiac tissue, the important principle of in vitro cell
      culture is to mimic the in vivo cell growth environment. Thus, micro-sized cells
      are more suitably cultured in three-dimensional (3D) than in two-dimensional (2D)
      microenvironments (ex: culture dish). With the matching dimensions of works
      produced by microfluidic technology, chemical engineering and biochemistry
      applications have used this technology extensively in cellular works. The 3D
      scaffolds produced in our investigation has essential properties, such has high
      mass transfer efficiency, and variable pore sizes, to adapt to various needs of
      different cell types. In addition to the malleability of these innovative
      scaffolds, fabrication procedure was effortless and fast. Primary neonatal mice
      cardiomyocytes were successfully harvested and cultured in 3D scaffolds made of
      gelatin and collagen. Gelatin and gelatin-collagen scaffold were produced by the
      formation of microbubbles through a microfluidic device, and the mechanical
      properties of gelatin scaffold and gelatin-collagen scaffold were measured.
      Cellular properties in the microbubbles were also monitored. Fluorescence
      staining results assured that cardiomyocytes could maintain in vivo morphology in
      3D gelatin scaffold. In addition, it was found that 3D scaffold could prolong the
      contraction behavior of cardiomyocytes compared with a conventional 2D culture
      dish. Spontaneously contracted behavior was maintained for the longest (about 1
      month) in the 3D gelatin scaffold, about 19 days in the 3D gelatin-collagen
      scaffold. To sum up, this 3D platform for cell culture has promising potential
      for myocardial tissue engineering. 

PMID- 24851798
TI  - Mapping of sheep sensory cortex with a novel microelectrocorticography grid.
AB  - Microelectrocorticography (uECoG) provides insights into the cortical
      organization with high temporal and spatial resolution desirable for better
      understanding of neural information processing. Here we evaluated the use of
      uECoG for detailed cortical recording of somatosensory evoked potentials (SEPs)
      in an ovine model. The approach to the cortex was planned using an MRI-based 3D
      model of the sheep's brain. We describe a minimally extended surgical procedure
      allowing placement of two different uECoG grids on the somatosensory cortex. With
      this small craniotomy, the frontal sinus was kept intact, thus keeping the
      surgical site sterile and making this approach suitable for chronic
      implantations. We evaluated the procedure for chronic implantation of an
      encapsulated uECoG recording system. During acute and chronic recordings,
      significant SEP responses in the triangle between the ansate, diagonal, and
      coronal sulcus were identified in all animals. Stimulation of the nose, upper
      lip, lower lip, and chin caused a somatotopic lateral-to-medial, ipsilateral
      response pattern. With repetitive recordings of SEPs, this somatotopic pattern
      was reliably recorded for up to 16 weeks. The findings of this study confirm the
      previously postulated ipsilateral, somatotopic organization of the sheep's
      sensory cortex. High gamma band activity was spatially most specific in the
      comparison of different frequency components of the somatosensory evoked
      response. This study provides a basis for further acute and chronic
      investigations of the sheep's sensory cortex by characterizing its exact
      position, its functional properties, and the surgical approach with respect to
      macroanatomical landmarks.

PMID- 24851799
TI  - Gender issues in antiepileptic drug treatment.
AB  - The purpose of this review is to discuss gender-related aspects in the,
      pharmacokinetics, effects, selection and use of antiepileptic drugs (AED). In
      general, there are few known gender related differences in pharmacokinetics or
      efficacy of AEDs. Conversely, gender has a significant influence on the
      susceptibility to certain adverse effects, not the least those involving
      alterations in sex hormone metabolism. Particularly relevant are the teratogenic
      effects of AEDs, with important differences among AEDs in their potential to
      cause adverse effects on the fetus when used during pregnancy. Pregnancy can also
      markedly affect the pharmacokinetics of several AEDs, and dose adjustments are
      often needed during pregnancy to maintain seizure control. Some treatments that
      are used only by women, such as contraceptive steroids and hormone replacement
      therapy, can also interact with AEDs to an extent that may affect the utilization
      of both the AEDs and the other drug.

PMID- 24851802
TI  - Childhood obsessive-compulsive traits in anorexia nervosa patients, their
      unaffected sisters and healthy controls: a retrospective study.
AB  - Although there is evidence that childhood perfectionistic traits predate the
      onset of eating disorders, few studies to date have examined the prevalence and
      clinical correlates of these traits in patients with anorexia nervosa (AN) and
      their unaffected sisters. The aim of this work was to study the prevalence of
      childhood obsessive-compulsive traits in patients with lifetime AN, their
      unaffected sisters and healthy women. A total of 116 AN patients, 32 healthy
      sisters and 119 controls were assessed by the EATATE Interview to assess traits
      such as perfectionism, inflexibility, rule-bound traits, drive for order and
      symmetry, and excessive doubt and cautiousness. Both self-report and maternal
      reports were collected. AN patients reported more childhood obsessive-compulsive
      traits than their healthy sisters and controls. In contrast, no differences
      between healthy controls and unaffected sisters emerged. In patients with AN, a
      dose-response relationship was found between the number of childhood obsessive
      compulsive traits and psychopathology, including body image distortion, thus
      indicating that these traits are an important feature to be considered in
      assessing and treating eating disorders.

PMID- 24851801
TI  - Immunotherapy targeting alpha-synuclein protofibrils reduced pathology in (Thy-1)
      h[A30P] alpha-synuclein mice.
AB  - Several lines of evidence suggest that accumulation of aggregated alpha-synuclein
      (alpha-synuclein) in the central nervous system (CNS) is an early pathogenic
      event in Parkinson's disease and other Lewy body disorders. In recent years,
      animal studies have indicated immunotherapy with antibodies directed against
      alpha-synuclein as a promising novel treatment strategy. Since large alpha
      synuclein oligomers, or protofibrils, have been demonstrated to possess
      pronounced cytotoxic properties, such species should be particularly attractive
      as therapeutic targets. In support of this, (Thy-1)-h[A30P] alpha-synuclein
      transgenic mice with motor dysfunction symptoms were found to display increased
      levels of alpha-synuclein protofibrils in the CNS. An alpha-synuclein protofibril
      selective monoclonal antibody (mAb47) was evaluated in this alpha-synuclein
      transgenic mouse model. As measured by ELISA, 14month old mice treated for
      14weeks with weekly intraperitoneal injections of mAb47 displayed significantly
      lower levels of both soluble and membrane-associated protofibrils in the spinal
      cord. Besides the lower levels of pathogenic alpha-synuclein demonstrated, a
      reduction of motor dysfunction in transgenic mice upon peripheral administration
      of mAb47 was indicated. Thus, immunotherapy with antibodies targeting toxic alpha
      synuclein species holds promise as a future disease-modifying treatment in
      Parkinson's disease and related disorders. 

PMID- 24851803
TI  - Impact of counselling on quality of life and sleep in cancer patients.
AB  - It has been acknowledged that poor quality of sleep significantly correlates with
      poor quality of life; evidence suggests that counselling has a positive impact
      not only on the cancer patient's quality of life, but also on family members and
      friends. The aim of this service evaluation was to determine if there was an
      improvement in clients' quality of life and sleep patterns following counselling
      as offered by a local cancer charity. A total of 60 matched pre- and post
      counselling questionnaires were completed and subjected to statistical analysis.
      When considering quality of life, in the domains of Role Emotional, Mental Health
      and Mental Component Summary Score, it can be concluded that counselling has a
      positive effect on emotional health and mental wellbeing. The mean total number
      of hours sleep per night significantly increased from 6 hours sleep per night at
      baseline to 6.8 hours sleep per night at the completion of counselling (p=0.005)
      showing clients gained an extra 48 minutes sleep per night. The improved
      emotional and mental wellbeing alongside the extra 48 minutes sleep per night
      provides evidence that there is a positive outcome for those patients and
      families who use counselling services. Nurses and other members of the
      multidisciplinary team should be encouraged to discuss supportive therapies with
      patients and those affected by cancer at all stages of the cancer trajectory,
      regardless of social status, gender or cancer type. 

PMID- 24851804
TI  - Pain management in cancer nursing.

PMID- 24851805
TI  - Challenges for the clinical nurse specialist in uro-oncology care.
AB  - Cancer is a complex illness that over the years has provoked much fear and
      speculation for patients, their relatives and health professionals. Emphasis has
      been placed on cancer management from the point of diagnosis, as well as
      treatments and their associated risks. As a result of increased technology and
      improved treatment modalities, more people are now surviving cancer and go on to
      live longer and healthier lives. While such an achievement is commendable, it
      places a significant strain on the healthcare economy. The Cancer Reform Strategy
      acknowledges that the management of cancers in the UK warrants clear definitive
      protocols and guidelines, to ensure a strategy that is capable of achieving the
      desired outcomes for those individuals who are affected by the disease. Integral
      to this objective is the multidisciplinary team, in which the role of the cancer
      nurse specialist is fundamental to achieving holistic patient outcomes. However,
      this article addresses the challenges of a uro-oncology clinical nurse specialist
      from a conceptual, as well as a personal, perspective. It focuses on the role
      that is specific to the management of patients who are diagnosed with urological
      cancers. 

PMID- 24851800
TI  - Sex dimorphism in seizure-controlling networks.
AB  - Males and females show a different predisposition to certain types of seizures in
      clinical studies. Animal studies have provided growing evidence for sexual
      dimorphism of certain brain regions, including those that control seizures.
      Seizures are modulated by networks involving subcortical structures, including
      thalamus, reticular formation nuclei, and structures belonging to the basal
      ganglia. In animal models, the substantia nigra pars reticulata (SNR) is the best
      studied of these areas, given its relevant role in the expression and control of
      seizures throughout development in the rat. Studies with bilateral infusions of
      the GABA(A) receptor agonist muscimol have identified distinct roles of the
      anterior or posterior rat SNR in flurothyl seizure control, that follow sex
      specific maturational patterns during development. These studies indicate that
      (a) the regional functional compartmentalization of the SNR appears only after
      the third week of life, (b) only the male SNR exhibits muscimol-sensitive
      proconvulsant effects which, in older animals, is confined to the posterior SNR,
      and (c) the expression of the muscimol-sensitive anticonvulsant effects become
      apparent earlier in females than in males. The first three postnatal days are
      crucial in determining the expression of the muscimol-sensitive proconvulsant
      effects of the immature male SNR, depending on the gonadal hormone setting.
      Activation of the androgen receptors during this early period seems to be
      important for the formation of this proconvulsant SNR region. We describe
      molecular/anatomical candidates underlying these age- and sex-related
      differences, as derived from in vitro and in vivo experiments, as well as by
      [(14)C]2-deoxyglucose autoradiography. These involve sex-specific patterns in the
      developmental changes in the structure or physiology or GABA(A) receptors or of
      other subcortical structures (e.g., locus coeruleus, hippocampus) that may affect
      the function of seizure-controlling networks.

PMID- 24851806
TI  - Social media and the changing face of cancer.

PMID- 24851807
TI  - Polymeric membrane dressings for radiotherapy-induced skin damage.
AB  - Radiotherapy is one of the mainline treatments for cancer. One of the side
      effects associated with radiotherapy includes skin problems, which range from
      mild (dull erythema and tightening of the skin) to severe (moist desquamation
      resulting in open wounds that can be very painful associated with sloughy and, in
      some severe cases, necrosis). The increased use of advanced radical treatments,
      such as intensity-modulated radiotherapy treatment (IMRT), can also result in a
      higher number of patients experiencing skin reactions. It is estimated that
      approximately 87% of patients will experience a moderate-to-severe skin reaction
      (Harris et al, 2011) An evaluation was undertaken in 20 patients with head and
      neck cancer following a prescribed treatment of radiotherapy to compare a
      polymeric membrane dressing (PolyMem(r)) against the standard treatment. The
      standard treatment consisted of topical aqueous cream at the start of
      radiotherapy with the addition of paraffin gauze when moist desquamation
      occurred. A bespoke evaluation form was completed for a period of 4 weeks or
      until healed. Patients were asked to complete both qualitative descriptions and
      numerical scores of pain for symptoms and procedural pain. Analgesia and sleep
      patterns were logged and, in addition, free text diaries were provided for up to
      4 weeks. Common themes were identified and qualitative data analysed.

PMID- 24851808
TI  - What would you consider 'good enough' as a patient?

PMID- 24851809
TI  - Using a soft-silicone dressing to treat moist desquamation.
AB  - Skin reactions are a common side effect of radiotherapy. Radiotherapy damages
      basal cells and skin reactions occur when the basal layer is unable to produce
      enough new cells to compensate for the loss of damaged cells at the skin's
      surface. Skin reactions progress from erythema, through dry desquamation to moist
      desquamation. As yet, there are no nationally recognised guidelines for the
      management of radiotherapy-induced skin reactions. As a result, there is
      widespread variation in practice throughout the UK. Hydrocolloid and hydrogel
      dressings have been used to treat moist desquamation. However, this article
      describes the successful clinical experience with an alternative dressing,
      Mepilex Lite(r). The clinical evidence presented also raises the question of
      whether Mepilex Lite can be used prophylactically as an alternative to aqueous
      cream on grade 1 (erythema) reactions. Further evidence on this indication for
      Mepilex Lite will be published in a BJN supplement in November 2014. 

PMID- 24851810
TI  - Graft-versus-host disease in oncology nursing practice.
AB  - INTRODUCTION: Gastrointestinal graft-versus-host disease (GI-GvHD) is extremely
      debilitating and is multifactorial in its causative factors, management and
      treatment. It is an exaggeration of normal physiological mechanisms wherein the
      donor immune system attempts to rid itself of the host. The inflammatory process
      that follows has the benefit of providing an anti-tumour effect for many
      diseases, but unfortunately in patients undergoing human stem-cell
      transplantation, the nature of the inflammation can result in disability, wasting
      and death. AIM: The aim of this article is to discuss the pathophysiology of this
      often misunderstood or misdiagnosed condition, as well as its signs and symptoms,
      management and considerations for nursing care. Considerations for nursing
      practice: While the medical management is aimed at minimising GvHD through the
      reduction of T-cell production and proliferation and gastrointestinal
      decolonisation, the nursing care is often focused on the signs and symptoms that
      can have the most prominent impact on patients. CONCLUSION: GI-GvHD has serious
      life-threatening complications, namely wasting syndrome, diarrhoea and
      dehydration. The basis of signs and symptomology is easily recognisable owing to
      the stages of progression through the human stem-cell transplantation process.
      Oncology nurses are in a prime position to identify these serious risks, initiate
      treatment immediately and collaborate effectively within the multidisciplinary
      team to minimise GvHD onset and provide expert support to patients, family and
      caregivers.

PMID- 24851812
TI  - Sulfuric acid hydrolysis and detoxification of red alga Pterocladiella capillacea
      for bioethanol fermentation with thermotolerant yeast Kluyveromyces marxianus.
AB  - One-step sulfuric acid saccharification of the red alga Pterocladiella capillacea
      was optimized, and various detoxification methods (neutralization, overliming,
      and electrodialysis) of the acid hydrolysate were evaluated for fermentation with
      the thermotolerant yeast Kluyveromyces marxianus. A proximate composition
      analysis indicated that P. capillacea was rich in carbohydrates. A significant
      galactose recovery of 81.1 +/- 5% was also achieved under the conditions of a 12%
      (w/v) biomass load, 5% (v/v) sulfuric acid, 121 degrees C, and hydrolysis for 30
      min. Among the various detoxification methods, electrodialysis was identified as
      the most suitable for fermentable sugar recovery and organic acid removal (100%
      reduction of formic and levulinic acids), even though it failed to reduce the
      amount of the inhibitor 5-HMF. As a result, K. marxianus fermentation with the
      electrodialyzed acid hydrolysate of P. capillacea resulted in the best ethanol
      levels and fermentation efficiency. 

PMID- 24851811
TI  - Systems analysis of West Nile virus infection.
AB  - Emerging and re-emerging mosquito-borne viruses continue to pose a significant
      threat to human health throughout the world. Over the past decade, West Nile
      virus (WNV), Dengue virus (DENV), and Chikungunya virus (CHIKV), have caused
      annual epidemics of virus-induced encephalitis, hemorrhagic fever?shock
      syndromes, and arthritis, respectively. Currently, no specific antiviral
      therapies or vaccines exist for use in humans to combat or prevent these viral
      infections. Thus, there is a pressing need to define the virus-host interactions
      that govern immunity and infection outcome. Recent technological breakthroughs in
      'omics' resources and high-throughput based assays are beginning to accelerate
      antiviral drug discovery and improve on current strategies for vaccine design. In
      this review, we highlight studies with WNV and discuss how traditional and
      systems biological approaches are being used to rapidly identify novel host
      targets for therapeutic intervention and develop a deeper conceptual
      understanding of the host response to virus infection. 

PMID- 24851813
TI  - Phenylpropanoids of plant origin as inhibitors of biofilm formation by Candida
      albicans.
AB  - Biofilm-related infections of Candida albicans are a frequent cause of morbidity
      and mortality in hospitalized patients, especially those with immunocompromised
      status. Options of the antifungal drugs available for successful treatment of
      drug-resistant biofilms are very few, and as such, new strategies need to be
      explored against them. The aim of this study was to evaluate the efficacy of
      phenylpropanoids of plant origin against planktonic cells, important virulence
      factors, and biofilm forms of C. albicans. Standard susceptibility testing
      protocol was used to evaluate the activities of 13 phenylpropanoids against
      planktonic growth. Their effects on adhesion and yeast-to-hyphae morphogenesis
      were studied in microplate-based methodologies. An in vitro biofilm model
      analyzed the phenylpropanoid-mediated prevention of biofilm development and
      mature biofilms using XTT-metabolic assay, crystal violet assay, and light
      microscopy. Six molecules exhibited fungistatic activity at <=0.5 mg/ml, of which
      four were fungicidal at low concentrations. Seven phenylpropanoids inhibited
      yeast-to-hyphae transition at low concentrations (0.031-0.5 mg/ml), whereas
      adhesion to the solid substrate was prevented in the range of 0.5-2 mg/ml.
      Treatment with <=0.5 mg/ml concentrations of at least six small molecules
      resulted in significant (p < 0.05) inhibition of biofilm formation by C.
      albicans. Mature biofilms that are highly resistant to antifungal drugs were
      susceptible to low concentrations of 4 of the 13 molecules. This study revealed
      phenylpropanoids of plant origin as promising candidates to devise preventive
      strategies against drug-resistant biofilms of C. albicans. 

PMID- 24851814
TI  - Distribution and characterization of integrons in enterobacteriaceae isolates
      from chickens in Korea.
AB  - The use of antimicrobial agents for additives or therapeutics is strongly
      associated with a prevalence of antimicrobial resistance in commensal
      Enterobacteriaceae. We aimed to characterize integrons in Enterobacteriaceae
      isolates obtained from chicken cecums in Korea. Moreover, the correlation between
      integron gene cassettes and antimicrobial resistance was also investigated. A
      total of 90 isolates the belonged to Enterobacteriaceae were recovered from
      chickens grown at Gyeongsang and Chungcheong provinces in Korea. Antimicrobial
      susceptibility tests were performed by the disk diffusion method. PCR and DNA
      sequencing were also performed to characterize the gene cassette arrays of the
      integrons. Of the 90 Enterobacteriaceae isolates tested, 39 (43.3%) and 10
      (11.1%) isolates carried class 1 and 2 integrons, respectively. Whereas the class
      2 integron did not contain gene cassettes, the class 1 integrons carried seven
      different gene cassette arrays. The class 1 integrons harbored genes encoding
      resistant determinants to aminoglycosides (aadA1, aadA2, and aadA5), trimethoprim
      (dfrA1, dfrA12, dfrA17, and dfrA32), lincosamides (linF), and erythromycin
      (ereA). Moreover, the presence of a class 1 integron was significantly related to
      a high resistance rate of antimicrobial agents, such as spectinomycin and
      trimethoprim. We confirmed that diverse class 1 integrons were widely distributed
      in Enterobacteriaceae isolates from chickens and directly contributed to the
      resistance to diverse antimicrobial agents in Korea. 

PMID- 24851816
TI  - Enzymatic synthesis of 2-phenoxyethanol galactoside by whole cells of beta
      galactosidase-containing Escherichia coli.
AB  - We investigated whether beta-galactosidase (beta-gal)-containing Escherichia coli
      cells could transfer a galactose to 2-phenoxyethanol, resulting in 2
      phenoxyethanol galactoside (PE-Gal). PE-Gal was confirmed by liquid
      chromatography-mass spectrometry. In addition, we also confirmed that a galactose
      molecule was covalently bonded with PE during thin-layer chromatography analysis
      of the beta-gal hydrolysate of PE-Gal. The yield for PE-Gal synthesis was about
      37.5% (weight basis), which was about 7-8 times greater than that of a previous
      report. In addition, the concentration of beta-gal (0.96 U/ml) used in this PE
      Gal synthesis was about 20 times less than that in a previous report. 

PMID- 24851815
TI  - Incorporation of Nasutitermes takasagoensis endoglucanase into cell surface
      displayed minicellulosomes in Pichia pastoris X33.
AB  - In this study, the yeast Pichia pastoris was genetically modified to assemble
      minicellulosomes on its cell surface by the heterologous expression of a
      truncated scaffoldin CipA from Clostridium acetobutylicum. Fluorescence
      microscopy and western blot analysis confirmed that CipA was targeted to the
      yeast cell surface and that NtEGD, the Nasutitermes takasagoensis endoglucanase
      that was fused with dockerin, interacted with CipA on the yeast cell surface,
      suggesting that the cohesin and dockerin domains and cellulose-binding module of
      C. acetobutylicum were functional in the yeasts. The enzymatic activities of the
      cellulases in the minicellulosomes that were displayed on the yeast cell surfaces
      increased dramatically following interaction with the cohesin-dockerin domains.
      Additionally, the hydrolysis efficiencies of NtEGD for carboxymethyl cellulose,
      microcrystal cellulose, and filter paper increased up to 1.4-fold, 2.0-fold, and
      3.2-fold, respectively. To the best of our knowledge, this is the first report
      describing the expression of C. acetobutylicum minicellulosomes in yeast and the
      incorporation of animal cellulases into cellulosomes. This strategy of
      heterologous cellulase incorporation lends novel insight into the process of
      cellulosome assembly. Potentially, the surface display of cellulosomes, such as
      that reported in this study, may be utilized in the engineering of S. cerevisiae
      for ethanol production from cellulose and additional future applications. 

PMID- 24851818
TI  - Pelvic inflammatory disease in China.

PMID- 24851817
TI  - Preparation and characterization of silver nanoparticles-loaded calcium alginate
      beads embedded in gelatin scaffolds.
AB  - Silver nanoparticles (AgNPs)-loaded alginate beads embedded in gelatin scaffolds
      were successfully prepared. The AgNPs-loaded calcium alginate beads were prepared
      by electrospraying method. The effect of alginate concentration and applied
      voltage on shape and diameter of beads was studied. The diameter of dry AgNPs
      loaded calcium alignate beads at various concentrations of AgNO3 ranged between
      154 and 171 MUm. The AgNPs-loaded calcium alginate beads embedded in gelatin
      scaffolds were fabricated by freeze-drying method. The water swelling and weight
      loss behaviors of the AgNPs-loaded alginate beads embedded in gelatin scaffolds
      increased with an increase in the submersion time. Moreover, the genipin-cross
      linked gelatin scaffolds were proven to be nontoxic to normal human dermal
      fibroblasts, suggesting their potential uses as wound dressings. 

PMID- 24851819
TI  - Evaluation of warfarin dose requirements in patients with chronic kidney disease
      and end-stage renal disease.
AB  - STUDY OBJECTIVES: The effect of chronic kidney disease (CKD) on warfarin has
      gained attention because of an increased risk of thromboembolism and an increased
      risk of bleeding associated with warfarin treatment in these patients. Data
      suggest that patients with reduced kidney function require lower warfarin doses;
      however, relatively few patients with end-stage renal disease (ESRD) were
      included in previous studies. The goal of this study was to evaluate warfarin
      dosing requirements and time to reach therapeutic international normalized ratio
      (INR) in patients with CKD stages 3-5 and ESRD compared with patients with normal
      kidney function (NKF). METHODS: A historical cohort was identified to evaluate
      warfarin response in 210 hospitalized adults with varying degrees of kidney
      function initiated or maintained on warfarin for 4 or more consecutive days
      including 49 patients with NKF (glomerular filtration rate [GFR] higher than 60
      ml/min/1.73 m(2) ), 44 with CKD stage 3, 27 with CKD stage 4/5, and 90 with ESRD.
      The average daily dose (ADD), time to achieve a therapeutic INR, and adverse
      effects were compared. MEASUREMENTS AND MAIN RESULTS: The ADD to maintain a
      therapeutic INR was 5.6 +/- 1.7 mg in the NKF group, 4.3 +/- 1.6 mg in CKD stage
      3, 4.6 +/- 1.9 mg in CKD stage 4/5, and 4.8 +/- 1.9 mg in ESRD. The ADD was lower
      in CKD/ESRD patients compared with NKF patients (p=0.001), especially among
      whites. The time to reach a therapeutic INR in patients newly initiated on
      warfarin was significantly lower in the CKD/ESRD group when compared with the NKF
      group (p=0.02). No differences in bleeding episodes were observed during
      hospitalization or within 30 days of discharge in patients with CKD stage 3 or
      higher compared with patients with NKF. CONCLUSIONS: Our findings suggest that
      CKD and ESRD patients require ~20% lower warfarin doses to maintain a therapeutic
      INR and may require less time to achieve a therapeutic INR compared with patients
      with NKF.

PMID- 24851820
TI  - Emotional and Behavioral Problems in Migrant Children and Adolescents in American
      Countries: A Systematic Review.
AB  - The present review postulates the current mental health status in migrant
      children and adolescents in the North American continent. 35 studies published
      from 2009 to 2013 chosen from a systematic literature research were included.
      Almost all studies were conducted in the United States and Canada. From the
      perspective of selection effect, migration as a risk factor was not proven. The
      migration process perspective could have underestimated a higher danger of
      problem behavior in second-generation migrant children. Comparing native and
      migrant children, balanced results in problem behavior were reported, but the
      Asian migrant group was at higher risk of developing mental disorders. Family
      based risk factors were offered: high acculturation stress, low English language
      competence, language brokering, discrepancies in children's and parent's cultural
      orientation, the non-Western cultural orientation, e.g., collectivistic,
      acceptance feelings of parents, or harsh parenting. However, the importance to
      support migrant families in the acculturation process becomes apparent. 

PMID- 24851821
TI  - Recognition of Risk Factors for Postpartum Depression in Refugee and Immigrant
      Women: Are Current Screening Practices Adequate?
AB  - Currently little is known of postpartum depression (PPD) screening and referral
      for refugee and immigrant women in Northern New England where the foreign born
      population has been rapidly expanding in the past decade. Research on PPD has
      focused largely on the general population leaving a large gap in our
      understanding of PPD in this vulnerable group. A retrospective chart review was
      conducted from a tertiary medical center with 1,160 births per year. Total sample
      n = 126, 28 % scored at risk for PPD. 39 % of women at risk had follow up
      documented as a phone call alone, however 43 % of that at risk group did not
      speak English. Focuses on the suitability of tools that have not been
      psychometrically tested for this population and may be culturally inappropriate
      for non western women. Lack of appropriate follow up is challenged and who is
      best placed to perform screening is considered. 

PMID- 24851823
TI  - Interplay between microdynamics and macrorheology in vesicle suspensions.
AB  - The microscopic dynamics of objects suspended in a fluid determines the
      macroscopic rheology of a suspension. For example, as shown by Danker and Misbah
      [Phys. Rev. Lett., 2007, 98, 088104], the viscosity of a dilute suspension of
      fluid-filled vesicles is a non-monotonic function of the viscosity contrast (the
      ratio between the viscosities of the internal encapsulated and the external
      suspending fluids) and exhibits a minimum at the critical point of the tank
      treading-to-tumbling transition. By performing numerical simulations, we recover
      this effect and demonstrate that it persists for a wide range of vesicle
      parameters such as the concentration, membrane deformability, or swelling degree.
      We also explain why other numerical and experimental studies lead to
      contradicting results. Furthermore, our simulations show that this effect even
      persists in non-dilute and confined suspensions, but that it becomes less
      pronounced at higher concentrations and for more swollen vesicles. For dense
      suspensions and for spherical (circular in 2D) vesicles, the intrinsic viscosity
      tends to depend weakly on the viscosity contrast. 

PMID- 24851822
TI  - Widening Life Expectancy Advantage of Hispanics in the United States: 1990-2010.
AB  - We examine trends in the Hispanic longevity advantage between 1990 and 2010,
      focusing on the contribution of cigarette smoking. We calculate life expectancy
      at age 50 for Hispanics and non-Hispanic whites between 1990 and 2010. We use an
      indirect method to calculate the contribution of smoking to changes over time in
      life expectancy. Among women, the Hispanic advantage in life expectancy grows
      from 2.14 years in 1990 (95 % CI 1.99-2.30 years) to 3.53 years in 2010 (3.42
      3.64 years). More than 40 % of this increase reflects widening differences in
      smoking-attributable mortality. The advantage for Hispanic men increases from
      2.27 years (2.14-2.41 years) to 2.91 years (2.81-3.01 years), although smoking
      makes only a small contribution. Despite persistent disadvantage, US Hispanics
      have increased their longevity advantage over non-Hispanic whites since 1990,
      much of which reflects the continuing importance of cigarette smoking to the
      Hispanic advantage. 

PMID- 24851824
TI  - Microflow injection potassium bioassay based on G-quadruplex DNAzyme-enhanced
      chemiluminescence.
AB  - By taking advantage of microflow injection chemiluminescence analysis, we
      developed a distinctive microfluidic bioassay method based on G-Quadruplex
      DNAzyme-enhanced chemiluminescence for the determination of K(+) in human serum.
      AGRO100, the G-rich oligonucleotide with high hemin binding affinity was
      primarily selected as a K(+) recognition element. In the presence of K(+),
      AGRO100 folded into G-quadruplex and bound hemin to form DNAzyme, which catalyzed
      the oxidation of luminol by H2 O2 to produce chemiluminescence. The intensity of
      chemiluminescence increased with the K(+) concentration. In the study, the
      DNAzyme showed both long-term stability and high catalytic activity; other common
      cations at their physiological concentration did not cause notable interference.
      With only 6.7 * 10(-13) mol of AGRO100 consumption per sample, a linear response
      of K(+) ranged from 1 to 300 umol/L, the concentration detection limit 0.69
      umol/L (S/N = 3) and the absolute detection limit 1.38 * 10(-12) mol were
      obtained. The precision of 10 replicate measurements of 60 umol/L K(+) was found
      to be 1.72% (relative standard deviation). The accuracy of the method was
      demonstrated by analyzing real human serum samples.

PMID- 24851825
TI  - Palivizumab for prophylaxis against respiratory syncytial virus infection in
      children with cystic fibrosis.
AB  - BACKGROUND: Respiratory syncytial virus infection causes acute lung infection in
      infants and young children worldwide, resulting in considerable morbidity and
      mortality. Children with cystic fibrosis are prone to recurrent lung
      inflammation, bacterial colonisation and subsequent chronic airway disease,
      putting them at risk for severe respiratory syncytial virus infections requiring
      intensive care and respiratory support. No treatment currently exists, hence
      prevention is important. Palivizumab is effective in reducing respiratory
      syncytial virus hospitalisation rates and is recommended for prophylaxis in high
      risk children with other conditions. It is unclear if palivizumab can prevent
      respiratory syncytial virus hospitalisations and intensive care unit admissions
      in children with cystic fibrosis. OBJECTIVES: To determine the efficacy and
      safety of palivizumab (Synagis((r))) compared with placebo, no prophylaxis or
      other prophylaxis, in preventing hospitalisation and mortality from respiratory
      syncytial virus infection in children with cystic fibrosis. SEARCH METHODS: We
      searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register
      and scanned references of the eligible study and related reviews.Date of last
      search: 17 March 2014. SELECTION CRITERIA: Randomised and quasi-randomised
      studies. DATA COLLECTION AND ANALYSIS: The authors independently extracted data
      and assessed risk of bias. MAIN RESULTS: One study (186 infants up to two years
      old) comparing five monthly doses of palivizumab (N = 92) to placebo (N = 94)
      over one respiratory syncytial virus season was identified and met our inclusion
      criteria. We judged there to be a low risk of bias with respect to the
      concealment of the randomization schedule (although it was not clear how this was
      generated) and to blinding of participants and study personnel. There is also a
      low risk of bias with regards to incomplete outcome data. However, we judged
      there to be a high risk of bias from selective reporting (summary statements
      presented but no data) and the fact that this industry-supported study has not
      been published as a full report in a peer-reviewed journal.At six months follow
      up, one participant in each group was hospitalised due to respiratory syncytial
      virus; there were no deaths in either group. In the palivizumab and placebo
      groups, 86 and 90 children experienced any adverse event, while five and four
      children had related adverse events respectively. Nineteeen children receiving
      palivizumab and 16 receiving placebo suffered serious adverse events; one
      participant receiving palivizumab discontinued due to this. At 12 months follow
      up, there were no significant differences between groups in number of Pseudomonas
      bacterial colonisations or change in weight-to-height ratio. AUTHORS'
      CONCLUSIONS: We identified one randomised controlled trial comparing five monthly
      doses of palivizumab to placebo in infants up to two years old with cystic
      fibrosis. While the overall incidence of adverse events was similar in both
      groups, it is not possible to draw firm conclusions on the safety and
      tolerability of respiratory syncytial virus prophylaxis with palivizumab in
      infants with cystic fibrosis. Six months after treatment, the authors reported no
      clinically meaningful differences in outcomes. Additional randomised studies are
      needed to establish the safety and efficacy of palivizumab in children with
      cystic fibrosis.

PMID- 24851827
TI  - Statin therapy improves long-term survival in non-ischaemic cardiomyopathy: a
      pooled analysis of 4500 patients.
AB  - Statin therapy has demonstrated a beneficial effect in patients with chronic
      heart failure. While the majority of patients with ischaemic cardiomyopathy are
      prescribed these drugs, studies have demonstrated that less than one fifth of
      patients with dilated cardiomyopathy are on regular statin therapy. We have
      performed a meta-analysis of 4500 patients from six studies (four randomised
      controlled trials). Our results demonstrate that statin therapy significantly
      improves long-term survival in patients with non-ischaemic heart failure {Hazard
      ratio for mortality 0.45 (0.33-0.62); p<0.0001; I(2)=41%; p-value for
      heterogeneity=0.13}. 

PMID- 24851826
TI  - Physical activity recommendations in patients with chronic obstructive pulmonary
      disease.
AB  - BACKGROUND: Physical activity recommendations are hardly studied in patients with
      chronic obstructive pulmonary disease (COPD), and specifically recommendations
      that are individualized to a patient's aerobic fitness level are not studied.
      OBJECTIVES: To compare individualized (relative) and nonindividualized (absolute)
      physical activity recommendations in patients with COPD and to assess whether
      there are differences between patients with mild to moderate and (very) severe
      COPD. METHODS: We compared 7 different physical activity recommendations that
      were described in the literature. Four recommendations were individualized based
      on the patient's aerobic fitness level measured by a maximal cycle ergometer
      test. Three recommendations were nonindividualized. The recommendations were
      measured with an accelerometer, pedometer or questionnaire in 115 patients with
      mild to very severe COPD (68% male, mean age 65 years, mean FEV1 58% predicted).
      RESULTS: The percentage of patients that met the different recommendations ranged
      from 22 to 86% and only 8 patients met all 7 recommendations. The agreement
      between the different recommendations was poor (intraclass correlation
      coefficient, 0.28). Individualizing the recommendations resulted in a higher
      number of patients with severe or very severe COPD meeting the individualized
      recommendations compared to the nonindividualized recommendations. In contrast,
      patients with mild to moderate COPD less frequently met the individualized
      recommendations. CONCLUSIONS: Our study showed that applying various physical
      activity recommendations with small differences in frequency, intensity or time
      led to large differences in the classification of patients with COPD into being
      sufficiently physically active or not. Consequently, the used recommendation will
      highly affect the proposed physical activity advice to the patient.

PMID- 24851828
TI  - Long-term screening for sleep apnoea in paced patients: preliminary assessment of
      a novel patient management flowchart by using automatic pacemaker indexes and
      sleep lab polygraphy.
AB  - BACKGROUND: The primary aim of this pilot study was to prospectively assess a
      flowchart to screen and diagnose paced patients (pts) affected by sleep apnoeas,
      by crosschecking indexes derived from pacemakers (minute ventilation sensor on
      board) with Sleep-Lab Polygraphy (PG) outcomes. Secondarily, "smoothed" long-term
      pacemaker indexes (all the information between two consecutive follow-up visits)
      have been retrospectively compared vs. standard short-term pacemaker indexes
      (last 24h) at each follow-up (FU) visit, to test their correlation and diagnostic
      concordance. METHODS: Data from long-term FU of 61 paced pts were collected. At
      each visit, the standard short-term apnoea+hypopnoea (PM_AHI) index was retrieved
      from the pacemaker memory. Patients showing PM_AHI >= 30 at least once during FU
      were proposed to undergo a PG for diagnostic confirmation. Smoothed pacemaker
      (PM_SAHI) indexes were calculated by averaging the overall number of
      apnoeas/hypopnoeas over the period between two FU visits, and retrospectively
      compared with standard PM_AHI. RESULTS: Data were available from 609 consecutive
      visits (overall 4.64 +/- 1.78 years FU). PM_AHI indexes were positive during FU
      in 40/61 pts (65.6%); 26/40 pts (65%) accepted to undergo a PG recording; Sleep
      Lab confirmed positivity in 22/26 pts (84.6% positive predictive value for
      PM_AHI). A strong correlation (r=0.73) and a high level of concordance were found
      between smoothed and standard indexes (multivariate analysis, Cohen's-k and Z
      score tests). CONCLUSIONS: Pacemaker-derived indexes may help in screening paced
      pts potentially affected by sleep apnoeas. Long-term "smoothed" apnoea indexes
      could improve the accuracy of pacemaker screening capability, even though this
      hypothesis must be prospectively confirmed by larger studies.

PMID- 24851829
TI  - Geriatric cardiac surgery: chronology vs. biology.
AB  - Cardiac surgery is increasingly performed in elderly patients, and whilst the
      incidence of common risk factors associated with poorer outcome increases with
      age, recent studies suggest that outcomes in this population may be better than
      is widely appreciated. As such, in this review we have examined the current
      evidence for common cardiac surgical procedures in patients aged over 70 years.
      Coronary artery bypass grafting (CABG) in the elderly has similar early safety to
      percutaneous intervention, though repeat revascularisation is lower. Totally
      avoiding instrumentation of the ascending aorta with off-pump techniques may also
      reduce the incidence of neurological injury. Aortic valve replacement (AVR)
      significantly improves quality of life and provides excellent short- and long
      term outcomes. Combined AVR and CABG carries higher risk but late survival is
      still excellent. Mini-sternotomy AVR in the elderly can provide comparable
      survival to full-sternotomy AVR. More accurate risk stratification systems are
      needed to appropriately select patients for transcatheter aortic valve
      implantation. Mitral valve repair is superior to replacement in the elderly,
      although choosing the most effective method is important for achieving maximal
      quality of life. Minimally-invasive mitral valve surgery in the elderly has
      similar postoperative outcomes to sternotomy-based surgery, but reduces hospital
      length of stay and return to activity. In operative candidates, surgical repair
      is superior to percutaneous repair. Current evidence indicates that advanced age
      alone is not a predictor of mortality or morbidity in cardiac surgery. Thus
      surgery should not be overlooked or denied to the elderly solely on the basis of
      their "chronological age", without considering the patient's true "biological
      age". 

PMID- 24851830
TI  - How wing kinematics affect power requirements and aerodynamic force production in
      a robotic bat wing.
AB  - Bats display a wide variety of behaviors that require different amounts of
      aerodynamic force. To control and modulate aerodynamic force, bats change wing
      kinematics, which, in turn, may change the power required for wing motion. There
      are many kinematic mechanisms that bats, and other flapping animals, can use to
      increase aerodynamic force, e.g. increasing wingbeat frequency or amplitude.
      However, we do not know if there is a difference in energetic cost between these
      different kinematic mechanisms. To assess the relationship between mechanical
      power input and aerodynamic force output across different isolated kinematic
      parameters, we programmed a robotic bat wing to flap over a range of kinematic
      parameters and measured aerodynamic force and mechanical power. We systematically
      varied five kinematic parameters: wingbeat frequency, wingbeat amplitude, stroke
      plane angle, downstroke ratio, and wing folding. Kinematic values were based on
      observed values from free flying Cynopterus brachyotis, the species on which the
      robot was based. We describe how lift, thrust, and power change with increases in
      each kinematic variable. We compare the power costs associated with generating
      additional force through the four kinematic mechanisms controlled at the
      shoulder, and show that all four mechanisms require approximately the same power
      to generate a given force. This result suggests that no single parameter offers
      an energetic advantage over the others. Finally, we show that retracting the wing
      during upstroke reduces power requirements for flapping and increases net lift
      production, but decreases net thrust production. These results compare well with
      studies performed on C. brachyotis, offering insight into natural flight
      kinematics. 

PMID- 24851831
TI  - Maternal nicotine exposure exacerbates neonatal hyperoxia-induced lung fibrosis
      in rats.
AB  - BACKGROUND: Maternal nicotine exposure increases lung collagen in fetal and
      newborn animals. Connective tissue growth factor (CTGF) plays a role in hyperoxia
      induced pulmonary fibrosis. OBJECTIVE: To determine whether pre- and postnatal
      nicotine exposure can augment CTGF expression and postnatal hyperoxia-induced
      lung fibrosis. METHODS: Nicotine was administered to pregnant Sprague-Dawley rats
      at a dose of 6 mg/kg/day from gestational days 7-21 (prenatal nicotine-treated
      group) and gestational day 7 to postnatal day 14 (pre- and postnatal nicotine
      treated group). A control group of pregnant dams was injected with an equal
      volume of saline. Within 12 h of birth, rats were exposed to room air or 1 week
      of >95% O2 and an additional 2 weeks of 60% O2 (3 weeks of hyperoxia). Lungs were
      taken for total collagen, CTGF expression and histological analyses. RESULTS: In
      each maternal treatment group, the rats reared in hyperoxia had a higher total
      collagen compared with rats reared in room air on postnatal days 7 and 21.
      Collagen content was significantly higher in rats born to pre- and postnatal
      nicotine-treated dams than rats born to saline-treated and prenatal nicotine
      treated dams on postnatal days 7 and 21. Pre- and postnatal nicotine exposure and
      neonatal hyperoxia exposure increased CTGF expression on postnatal days 7 and 21.
      CONCLUSIONS: CTGF may be involved in the pathogenesis of lung fibrosis induced by
      maternal nicotine and neonatal hyperoxia, and maternal nicotine exposure
      exacerbates neonatal hyperoxia-induced lung fibrosis. These results are relevant
      to neonates who require supplemental oxygen and are exposed to the breast milk of
      smoking mothers during infancy.

PMID- 24851832
TI  - The morphological growth patterns of colorectal liver metastases are prognostic
      for overall survival.
AB  - Colorectal metastases in the liver grow according to three histological patterns:
      a pushing pattern, a replacement pattern, and a desmoplastic pattern. The
      objective of the current study was to explore the prognostic significance of
      these three growth patterns for survival. The study included 217 consecutive
      patients, liver resected between 2007 and 2011 due to hepatic metastases from
      colorectal adenocarcinoma. The growth patterns were assessed on archival
      hematoxylin and eosin-stained tissue sections. In 150 metastases, the density of
      the immune cell infiltrate at the tumor periphery was judged by a semi
      quantitative method. The prevalence of the pushing-type, the desmoplastic-type,
      and the replacement-type was 33%, 32%, and 11%, respectively; 24% of the
      metastases displayed a mixed pattern. Kaplan-Meier analysis and Cox regression
      demonstrated a prognostic significance of the growth patterns (P=0.0006, log-rank
      test), as the replacement pattern appeared as an independent predictor of poor
      overall survival. For patients with replacement growth, the hazard of death was 2
      2.5 times higher than for patients with pushing growth (P=0.004, cox regression)
      or mixed growth (P=0.01), and nearly four times higher than for patients with
      desmoplastic growth (P<0.0001). The negative prognostic effect of the replacement
      growth pattern was even more pronounced after adjusting for tumor size.
      Desmoplastic growth corresponded with small tumor size, dense lymphocytic
      infiltration and a more favorable prognosis. Eventually, the growth patterns may
      contribute to a histology-based prognostic biomarker for patients with colorectal
      liver metastases. 

PMID- 24851833
TI  - NUT midline carcinomas in the thymic region.
AB  - NUT midline carcinomas (NMCs) are rare tumors described predominantly in the
      pediatric age group. We recently reported two cases of these tumors occurring in
      the thymic region. In order to establish the true incidence of these tumors, we
      examined a large series of thymic carcinomas for morphological features of NUT
      tumor and further assessed the expression of NUTM1 (also known as NUT) protein by
      immunohistochemistry. The histological review of slides from 110 cases of thymic
      carcinoma was undertaken to identify carcinomas with mixed undifferentiated and
      squamous features that are typically associated with NUT carcinomas. The
      presenting symptoms, morphological spectrum of tumors and outcome data of
      patients with these histologies are presented. Immunohistochemistry for NUTM1 was
      performed on 35 cases of thymic carcinoma with available blocks (3 with these
      histological features and 32 without these features) to exclude the possibility
      of midline carcinoma. Tumors from 10 patients had features of mixed small cell
      undifferentiated squamous cell carcinoma (M:F, 1.5:1; age range, 22-79). These
      patients predominantly presented with advanced disease and had respiratory
      related symptoms or chest pain; four had paraneoplastic syndromes. The squamous
      component in all cases was well differentiated with little or no atypia. The
      undifferentiated component varied in cell size and lacked characteristic features
      of small cell carcinoma. All but one patients developed metastases or died within
      3 years of diagnosis. NUTM1 expression was seen in two of three tumors with these
      histological features and in none of the 32 cases without. Mixed small cell
      undifferentiated carcinomas share histological and immunohistochemical similarity
      with NMCs and have aggressive clinical course. These tumors are not uncommon and
      should be considered in the differential diagnosis of carcinomas in the thymic
      region as novel therapies might be available. 

PMID- 24851834
TI  - Cytochrome P450-catalyzed dealkylation of atrazine by Rhodococcus sp. strain
      NI86/21 involves hydrogen atom transfer rather than single electron transfer.
AB  - Cytochrome P450 enzymes are responsible for a multitude of natural transformation
      reactions. For oxidative N-dealkylation, single electron (SET) and hydrogen atom
      abstraction (HAT) have been debated as underlying mechanisms. Combined evidence
      from (i) product distribution and (ii) isotope effects indicate that HAT, rather
      than SET, initiates N-dealkylation of atrazine to desethyl- and
      desisopropylatrazine by the microorganism Rhodococcus sp. strain NI86/21. (i)
      Product analysis revealed a non-selective oxidation at both the alphaC and betaC
      atom of the alkyl chain, which is expected for a radical reaction, but not SET.
      (ii) Normal (13)C and (15)N as well as pronounced (2)H isotope effects
      (epsiloncarbon: -4.00/00 +/- 0.20/00; epsilonnitrogen: -1.40/00 +/- 0.30/00,
      KIEH: 3.6 +/- 0.8) agree qualitatively with calculated values for HAT, whereas
      inverse (13)C and (15)N isotope effects are predicted for SET. Analogous results
      are observed with the Fe(iv)[double bond, length as m-dash]O model system
      [5,10,15,20-tetrakis(pentafluorophenyl)porphyrin-iron(iii)-chloride + NaIO4], but
      not with permanganate. These results emphasize the relevance of the HAT mechanism
      for N-dealkylation by P450. 

PMID- 24851835
TI  - [German Resuscitation Register : lots of quality management at low cost].

PMID- 24851836
TI  - [Perioperative management of patients with obstructive sleep apnea : update on
      the practice guidelines of the American Society of Anesthesiologists Task Force].
AB  - Obstructive sleep apnea (OSA) is a widespread disease which is associated with
      many cardiovascular diseases and can have health-related consequences for
      affected patients if untreated. It is known that perioperative airway
      complications occur more often in OSA patients during general anesthesia. Some
      years ago the Task Force of the American Society of Anesthesiologists (ASA)
      published practice guidelines on the perioperative approach to OSA patients.
      These guidelines have now been revised and updated. This article gives a summary
      of the recommended approach for the perioperative treatment of patients with OSA
      given in the 2014 guidelines. 

PMID- 24851837
TI  - Factors in relation to bone mineral density in Korean middle-aged and older men:
      2008-2010 Korea National Health and Nutrition Examination Survey.
AB  - BACKGROUND/AIMS: Studies on determinants of bone mineral density (BMD) among
      Asian middle-aged and older men are very limited. The aim of this study was to
      investigate general determinants and dietary factors influencing BMD in Korean
      middle-aged and older men. METHODS: This study was conducted using data from the
      2008-2010 Korea National Health and Nutrition Examination Survey. A total of
      2,305 male subjects aged 50-79 years were included. Whole-body, total femur,
      femoral neck, and lumbar spine BMDs were measured by dual-energy X-ray
      absorptiometry. Dietary intake was estimated by 24-hour dietary recall. A food
      frequency questionnaire for 63 food items was also administered. RESULTS:
      Proportions of osteoporosis at the total femur, femoral neck, and lumbar spine
      were 0.7, 3.3 and 7.0%, respectively. Age, height, weight, body mass index, fat
      mass, lean body mass, waist circumference, serum vitamin D, parathyroid hormone,
      and exercise were related to BMD, but the relationships were site specific. Diet
      quality and intake of vegetables, fruits, and calcium were associated with BMD.
      CONCLUSIONS: These results suggest that a high-quality diet, an adequate intake
      of fruits, vegetables, and calcium, as well as exercise, high serum vitamin D and
      weight maintenance might be determinants of BMD among middle-aged and older Asian
      men.

PMID- 24851838
TI  - Neuroprotection elicited by P2Y13 receptors against genotoxic stress by inducing
      DUSP2 expression and MAPK signaling recovery.
AB  - Nucleotides activating P2Y13 receptors display neuroprotective actions against
      different apoptotic stimuli in cerebellar granule neurons. In the present study,
      P2Y13 neuroprotection was analyzed in conditions of genotoxic stress. Exposure to
      cisplatin and UV radiation induced caspase-3-dependent apoptotic cell death, and
      p38 MAPK signaling de-regulation. Pre-treatment with P2Y13 nucleotide agonist,
      2methyl-thio-ADP (2MeSADP), restored granule neuron survival and prevented p38
      long-lasting activation induced by cytotoxic treatments. Microarray gene
      expression analysis in 2MeSADP-stimulated cells revealed over-representation of
      genes related to protein phosphatase activity. Among them, dual-specificity
      phosphatase-2, DUSP2, was validated as a transcriptional target for P2Y13
      receptors by QPCR. This effect could explain 2MeSADP ability to dephosphorylate a
      DUSP2 substrate, p38, reestablishing the inactive form. In addition, cisplatin
      induced p38 sustained activation correlated perfectly with progressive reduction
      in DUSP2 expression. In conclusion, P2Y13 receptors regulate DUSP2 expression and
      contribute to p38 signaling homeostasis and survival in granule neurons. 

PMID- 24851839
TI  - Modulation of NRF2 signaling pathway by nuclear receptors: implications for
      cancer.
AB  - Nuclear factor-erythroid 2 p45-related factor 2 (NRF2, also known as Nfe2l2)
      plays a critical role in regulating cellular defense against electrophilic and
      oxidative stress by activating the expression of an array of antioxidant response
      element-dependent genes. On one hand, NRF2 activators have been used in clinical
      trials for cancer prevention and the treatment of diseases associated with
      oxidative stress; on the other hand, constitutive activation of NRF2 in many
      types of tumors contributes to the survival and growth of cancer cells, as well
      as resistance to anticancer therapy. In this review, we provide an overview of
      the NRF2 signaling pathway and discuss its role in carcinogenesis. We also
      introduce the inhibition of NRF2 by nuclear receptors. Further, we address the
      biological significance of regulation of the NRF2 signaling pathway by nuclear
      receptors in health and disease. Finally, we discuss the possible impact of NRF2
      inhibition by nuclear receptors on cancer therapy. 

PMID- 24851841
TI  - A roadmap for CAM research towards the horizon of 2020.

PMID- 24851840
TI  - Enhanced rate of degradation of basic proteins by 26S immunoproteasomes.
AB  - Immunoproteasomes are alternative forms of proteasomes specialized in the
      generation of MHC class I antigenic peptides and important for efficient cytokine
      production. We have identified a new biochemical property of 26S
      immunoproteasomes, namely the ability to hydrolyze basic proteins at greatly
      increased rates compared to constitutive proteasomes. This enhanced degradative
      capacity is specific for basic polypeptides, since substrates with a lower
      content in lysine and arginine residues are hydrolyzed at comparable rates by
      constitutive and immunoproteasomes. Crucially, selective inhibition of the
      immunoproteasome tryptic subunit beta2i strongly reduces degradation of basic
      proteins. Therefore, our data demonstrate the rate limiting function of the
      proteasomal trypsin-like activity in controlling turnover rates of basic protein
      substrates and suggest new biological roles for immunoproteasomes in maintaining
      cellular homeostasis by rapidly removing a potentially harmful excess of free
      histones that can build up under different pathophysiological conditions. 

PMID- 24851842
TI  - Before and after CAMbrella.

PMID- 24851843
TI  - Experimental models of integrative healthcare in a regional health system: a
      complex innovation path.

PMID- 24851844
TI  - A plant-derived wound therapeutic for cost-effective treatment of post-surgical
      scalp wounds with exposed bone.
AB  - BACKGROUND: To evaluate efficacy and cost-effectiveness of a plant-derived wound
      dressing (ONE), a mixture of hypericum oil (Hypericum perforatum L.) and neem oil
      (Azadirachta indica A. Juss.), in scalp wounds with exposed bone. PATIENTS AND
      METHODS: All patients with scalp wounds with exposed bone, following the excision
      of skin tumors, and treated with ONE in 2011 were included. Time of healing,
      wound size, area of exposed bone, ease of handling, pain, and complications were
      evaluated. Costs of dressings and nursing time were compared with those cited in
      literature for other treatment modalities. RESULTS: Fifteen consecutive patients
      with a mean age of 76.87 +/- 10.3 years (59-90 years) were analyzed. The mean
      wound size was 10.9 +/- 6.84 cm(2) (0.4-22.6 cm(2)) with 4.8 +/- 5.9 cm(2) (0.3
      20.7 cm(2)) of exposed bone. The time of complete healing by secondary intention
      was 8.1 (4-20) weeks. Rapid formation of granulation tissue was observed which
      after 4 weeks covered the entire exposed bone surface in 11 of 15 cases (73%).
      Dressing change was simple with no pain reported; no infections or other
      complications occurred. Using ONE for a mean healing time of 56.7 days resulted
      in mean costs of EUR 423.73, which is substantially lower than those published
      for fascia lata, negative pressure therapy, or collagen matrix followed by skin
      grafting (EUR 1,612.82, EUR 4,411.80 and EUR 1,503.72, respectively). CONCLUSION:
      This retrospective, non-controlled analysis supports ONE as a simple-to-use and
      safe treatment option for scalp wounds with exposed bone. Treatment costs compare
      favorably to those published for other treatment modalities.

PMID- 24851845
TI  - An earplug technique to reduce the gag reflex during dental procedures.
AB  - BACKGROUND: The gag reflex is a frequent problem occurring during dental
      treatment procedures, especially while making impressions of the maxillary teeth.
      The present study aims to evaluate the efficacy of a simple earplug as an
      external auditory canal stimulator to supress the profound gag reflex and as a
      second step, to map areas of the oropharynx suppressed by this technique.
      METHODS: In the first step of the study, 90 patients who had a gag reflex during
      the impression procedure were allocated to a study group, a sham group, and a
      control group for evaluating the efficacy of the earplug technique. Second, 20
      new patients with a gag reflex were included in order to map the oropharnygeal
      areas suppressed by this technique. RESULTS: The severity of the gag reflex was
      reduced in the earplug group (but not in the sham or the control group). The
      affected area included the hard palate, uvula, and the tongue but not the
      posterior wall of oropharynx. CONCLUSION: An earplug technique can be a useful,
      practical, and effective tool to overcome the gag reflex during oral procedures,
      such as impression procedures of maxillary teeth.

PMID- 24851846
TI  - Different cerebral responses to puncturing at ST36 among patients with functional
      dyspepsia and healthy subjects.
AB  - BACKGROUND: Little research has been done on the connection between functional
      status and acupuncture efficacy; however, functional status is a key factor in
      the study of acupuncture efficacy. Therefore, we have tried to compare functional
      dyspepsia (FD) patients with healthy subjects (HS) to determine the different
      cerebral responses elicited by acupuncture stimulation at Zusanli (ST36).
      PATIENTS AND METHODS: IN this study, 24 FD patients and 24 HS were given
      acupuncture stimulation at ST36 while being monitored by an fMRI scan. RESULTS:
      Compared with HS, FD patients showed an fMRI signal decrease in the right
      anterior cingulate cortex, right medial prefrontal cortex, right orbitofrontal
      cortex, left superior occipital gyrus, and right cuneus; but on the other hand,
      there was an fMRI signal increase in the right insula, right postcentral gyrus,
      and right supramarginal gyrus. CONCLUSION: Acupuncture stimulation at ST36 evoked
      pronounced changes, especially in the homeostatic afferent processing network of
      FD patients, compared to HS. We hypothesize that the cerebral responses elicited
      by acupuncture stimulation in certain diseases, such as FD are correlated to
      specific regions. The action of stimulating acupoints might be dynamic; the
      functional status is therefore an essential impact factor for cerebral responses
      to acupuncture stimulation.

PMID- 24851847
TI  - Stress-relieving effects of short-term balneotherapy - a randomized controlled
      pilot study in healthy adults.
AB  - BACKGROUND: Stress-relieving effects of balneotherapy compared to progressive
      muscle relaxation (PMR) and to resting were investigated by measuring subjective
      relaxation and salivary cortisol. It was also examined whether participants with
      a high versus low stress level would have a different relaxation response.
      METHODS: A sample of healthy volunteers was randomized to balneotherapy, PMR, or
      a resting control group, each intervention lasting for 25 min. Pre- and post
      intervention salivary cortisol samples were collected, and participants rated
      their status of relaxation on a quantitative scale. In addition, 3 questionnaires
      were applied to detect participants' stress level and bodily complaints. RESULTS:
      49 healthy participants were recruited (65.3% female). In a pre-post comparison,
      salivary cortisol decreased (F = 23.53, p < 0.001) and subjective relaxation
      ratings increased (F = 132.18, p < 0.001) in all 3 groups. Study participants in
      the balneotherapy group rated themselves as more relaxed after the intervention
      as compared to the other groups (F = 5.22, p < 0.009). Participants with a high
      versus low stress level differed in somatic symptoms and in morning cortisol
      levels, but showed a similar relaxation response. CONCLUSION: Findings suggest
      that compared to PMR and resting, balneotherapy seems to be more beneficial with
      regard to subjective relaxation effects and similarly beneficial with regard to a
      decrease in salivary cortisol.

PMID- 24851848
TI  - [The use of complementary and alternative therapies in Germany - a systematic
      review of nationwide surveys].
AB  - In this systematic review we aimed to summarize surveys investigating the use of
      complementary and alternative medicine (CAM) methods in the general German
      population and by physicians and lay practitioners. Nationwide surveys (using
      random, panel, or quota sampling methods) published since 1993 investigating the
      CAM use among the population and healthcare providers in Germany were identified
      through searches in PubMed, Google Scholar, Google, citation screening, and
      expert contacts. In addition we collected publicly available data from official
      nationwide health statistics and market statistics. 16 surveys of the general
      adult population and 4 surveys among physicians met inclusion criteria. The use
      of CAM among general population in the previous years varied between 40 and 62%.
      General practitioners and orthopedic specialists in private practice seem to
      provide CAM therapies widely and more frequently than other physician groups,
      with herbal medicine and chirotherapy being the most frequently used treatments.
      We could not identify any surveys of lay practitioners. The available surveys
      provide clear evidence of the widespread use of CAM methods in Germany both by
      the general population and by physicians. In recent years the use of CAM methods
      does not seem to increase any longer; for some methods (particularly herbal
      remedies) the use seems to be declining.

PMID- 24851849
TI  - Management of insomnia in traditional Persian medicine.
AB  - Insomnia is a sleep disorder which affects 10-48% of general population.
      Different measures, such as pharmacotherapy and behavioral management, are
      applied for insomnia and associated complaints. In traditional medical systems,
      herbal medicines are considered beneficial. Therefore, the present paper compiles
      pharmacological and medical insights into the management of insomnia according to
      Traditional Persian Medicine. Herein, preserved medical and pharmaceutical
      manuscripts of Persian medicine from 10th to 18th century A.D. were investigated
      for information about concepts of insomnia treatment and herbal remedies.
      Additionally, for all herbal remedies, an extensive search of scientific
      databases, such as MEDLINE and Scopus, has been performed to find related works
      concerning hypnotic, sedative, and anxiolytic as well as narcoleptic effects.
      Insomnia (generally called Sahar in Persian manuscripts) is a well-known
      disorder. Herbal medical intervention was the major treatment prescribed by
      Iranian physicians. Totally, 36 medicinal herbs related to 25 plant families are
      derived from the searched literature. These remedies were applied orally,
      topically, and nasally. Based on scientific data, 50% of reported herbs have
      relevant pharmacological effects. Besides historical elucidation, this paper
      presents medical and pharmacological approaches that had been applied by Persian
      practitioners in order to deal with sleep complications. Considering the fruitful
      results of these findings, this essay should encourage researchers to conduct
      more investigations in this field in order to understand the mechanisms and
      effects of traditionally applied herbs still unknown to modern medicine.

PMID- 24851850
TI  - [A research roadmap for complementary and alternative medicine - what we need to
      know by 2020].
AB  - BACKGROUND: The CAMbrella coordination action was funded within the Framework
      Programme 7. Its aim is to provide a research roadmap for clinical and
      epidemiological research for complementary and alternative medicine (CAM) that is
      appropriate for the health needs of European citizens and acceptable to their
      national research institutes and healthcare providers in both public and private
      sectors. One major issue in the European research agenda is the demographic
      change and its impact on health care. Our vision for 2020 is that there is an
      evidence base that enables European citizens to make informed decisions about
      CAM, both positive and negative. This roadmap proposes a strategic research
      agenda for the field of CAM designed to address future European health care
      challenges. This roadmap is based on the results of CAMbrella's several work
      packages, literature reviews and expert discussions including a consensus
      meeting. METHODS: We first conducted a systematic literature review on key issues
      in clinical and epidemiological research in CAM to identify the general concepts,
      methods and the strengths and weaknesses of current CAM research. These findings
      were discussed in a workshop (Castellaro, Italy, September 7-9th 2011) with
      international CAM experts and strategic and methodological recommendations were
      defined in order to improve the rigor and relevance of CAM research. These
      recommendations provide the basis for the research roadmap, which was
      subsequently discussed in a consensus conference (Jarna, Sweden, May 9-11th 2012)
      with all CAMbrella members and the CAMbrella advisory board. The roadmap was
      revised after this discussion in CAMbrella Work Package (WP) 7 and finally
      approved by CAMbrella's scientific steering committee on September 26th 2012.
      RESULTS: Our main findings show that CAM is very heterogenous in terms of
      definitions and legal regulations between the European countries. In addition,
      citizens' needs and attitudes towards CAM as well as the use and provision of CAM
      differ significantly between countries. In terms of research methodology, there
      was consensus that CAM researchers should make use of all the commonly accepted
      scientific research methods and employ those with utmost diligence combined in a
      mixed methods framework. CONCLUSIONS: We propose 6 core areas of research that
      should be investigated to achieve a robust knowledge base and to allow
      stakeholders to make informed decisions. These are: Research into the prevalence
      of CAM in Europe: Reviews show that we do not know enough about the circumstances
      in which CAM is used by Europeans. To enable a common European strategic
      approach, a clear picture of current use is of the utmost importance. Research
      into differences regarding citizens' attitudes and needs towards CAM: Citizens
      are the driver for CAM utilization. Their needs and views on CAM are a key
      priority, and their interests must be investigated and addressed in future CAM
      research. Research into safety of CAM: Safety is a key issue for European
      citizens. CAM is considered safe, but reliable data is scarce although urgently
      needed in order to assess the risk and cost-benefit ratio of CAM. Research into
      the comparative effectiveness of CAM: Everybody needs to know in what situation
      CAM is a reasonable choice. Therefore, we recommend a clear emphasis on
      concurrent evaluation of the overall effectiveness of CAM as an additional or
      alternative treatment strategy in real-world settings. Research into effects of
      context and meaning: The impact of effects of context and meaning on the outcome
      of CAM treatments must be investigated; it is likely that they are significant.
      Research into different models of CAM health care integration: There are
      different models of CAM being integrated into conventional medicine throughout
      Europe, each with their respective strengths and limitations. These models should
      be described and concurrently evaluated; innovative models of CAM provision in
      health care systems should be one focus for CAM research. We also propose a
      methodological framework for CAM research. We consider that a framework of mixed
      methodological approaches is likely to yield the most useful information. In this
      model, all available research strategies including comparative effectiveness
      research utilising quantitative and qualitative methods should be considered to
      enable us to secure the greatest density of knowledge possible. Stakeholders,
      such as citizens, patients and providers, should be involved in every stage of
      developing the specific and relevant research questions, study design and the
      assurance of real-world relevance for the research. Furthermore, structural and
      sufficient financial support for research into CAM is needed to strengthen CAM
      research capacity if we wish to understand why it remains so popular within the
      EU. In order to consider employing CAM as part of the solution to the health
      care, health creation and self-care challenges we face by 2020, it is vital to
      obtain a robust picture of CAM use and reliable information about its cost,
      safety and effectiveness in real-world settings. We need to consider the
      availability, accessibility and affordability of CAM. We need to engage in
      research excellence and utilise comparative effectiveness approaches and mixed
      methods to obtain this data. Our recommendations are both strategic and
      methodological. They are presented for the consideration of researchers and
      funders while being designed to answer the important and implicit questions posed
      by EU citizens currently using CAM in apparently increasing numbers. We propose
      that the EU actively supports an EU-wide strategic approach that facilitates the
      development of CAM research. This could be achieved in the first instance through
      funding a European CAM coordinating research office dedicated to foster
      systematic communication between EU governments, public, charitable and industry
      funders as well as researchers, citizens and other stakeholders. The aim of this
      office would be to coordinate research strategy developments and research funding
      opportunities, as well as to document and disseminate international research
      activities in this field. With the aim to develop sustainability as second step,
      a European Centre for CAM should be established that takes over the monitoring
      and further development of a coordinated research strategy for CAM, as well as it
      should have funds that can be awarded to foster high quality and robust
      independent research with a focus on citizens health needs and pan-European
      collaboration. We wish to establish a solid funding for CAM research to
      adequately inform health care and health creation decision-making throughout the
      EU. This centre would ensure that our vision of a common, strategic and
      scientifically rigorous approach to CAM research becomes our legacy and Europe's
      reality. We are confident that our recommendations will serve these essential
      goals for EU citizens.

PMID- 24851851
TI  - Regulating chondrogenesis of human mesenchymal stromal cells with a retinoic Acid
      receptor-Beta inhibitor: differential sensitivity of chondral versus
      osteochondral development.
AB  - AIM: Main objective was to investigate whether the synthetic retinoic acid
      receptor (RAR)-beta antagonist LE135 is able to drive in vitro chondrogenesis of
      human mesenchymal stromal cells (MSCs) or improve differentiation by suppressing
      hypertrophic chondrocyte development. METHODS: Chondrogenesis of human bone
      marrow and adipose tissue-derived MSCs was induced in micromass pellet culture
      for six weeks. Effects of LE135 alone and in combinatorial treatment with TGF
      beta on deposition of cartilaginous matrix including collagen type II and
      glycosaminoglycans, on deposition of non-hyaline cartilage collagens type I and
      X, and on hypertrophy markers including alkaline phosphatase (ALP), indian
      hedghehog (IHH) and matrix metalloproteinase (MMP)-13 were assessed. RESULTS:
      LE135 was no inducer of chondrogenesis and failed to stimulate deposition of
      collagen type II and glycosaminoglycans. Moreover, addition of LE135 to TGF-beta
      treated pellets inhibited cartilaginous matrix deposition and gene expression of
      COL2A1. In contrast, non-hyaline cartilage collagens were less sensitive to LE135
      and hypertrophy markers remained unaffected. CONCLUSION: This demonstrates a
      differential sensitivity of chondral versus endochondral differentiation pathways
      to RARbeta signaling; however, opposite to the desired direction. The relevance
      of trans-activating versus trans-repressing RAR signaling, including effects on
      activator protein (AP)-1 is discussed and implications for overcoming current
      limits of hMSC chondrogenesis are considered.

PMID- 24851854
TI  - Retraction note: strategies for efficient production of heterologous proteins in
      Escherichia coli.

PMID- 24851853
TI  - Angiotensin-converting enzyme gene polymorphisms and risk for sporadic
      Alzheimer's disease: a meta-analysis.
AB  - Numerous studies have tested for associations between common polymorphisms of the
      angiotensin-converting enzyme gene and sporadic Alzheimer disease (SAD), but
      results have been inconclusive. Using meta-analysis, our study aimed to clarify
      the nature of the genetic risks contributed by the three polymorphisms (rs4291,
      rs4343, rs1800764) for developing SAD. Through searching of Pubmed, Embase,
      Alzgene and manually searching relevant references, a total of 14 articles with
      26 independent studies were included. Odds ratios (ORs) with 95% confidence
      intervals (CIs) were used to assess the strength of the association studies. The
      heterogeneity across the studies was tested, as was publication bias. We observed
      significant association between SNP rs4291 and SAD using allelic comparison (OR =
      1.08, 95% CI 1.03-1.14), homozygote comparison (OR = 1.16, 95% CI 1.04-1.30) and
      the recessive model (OR = 1.10, 95% CI 1.02-1.18). Association with SNP rs1800764
      was revealed but it was not sufficiently robust to withstand the Benjamini
      Hochberg method and stepdown Bonferroni correction. Significant association was
      not identified in the analysis for SNP rs4343. In subgroup analyses, the risk of
      SAD associated with SNP rs4291 appeared to be significant among Caucasians and in
      older cases (mean age >=75 years). Our results confirmed a significant but modest
      association between SNP rs4291 and SAD susceptibility. Further study of the
      pathogenetic characteristics of this polymorphism and independent confirmation of
      the association in larger studies are warranted.

PMID- 24851855
TI  - Testing for pediatric obstructive sleep apnea when health care resources are
      rationed.
AB  - IMPORTANCE: Evaluation of pediatric obstructive sleep apnea in resource-limited
      health care systems necessitates testing modalities that are accurate and more
      cost-effective than polysomnography. OBJECTIVE: To trace the clinical pathway of
      children referred to our sleep laboratory for possible obstructive sleep apnea
      who were evaluated using nocturnal pulse oximetry and the McGill Oximetry Score.
      DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective cohort study of
      children 2 to 17 years old with suspected obstructive sleep apnea due to
      adenotonsillar hypertrophy, conducted at a Canadian pediatric tertiary care
      center. INTERVENTIONS: Nocturnal pulse oximetry studies scored using the McGill
      Oximetry Score. MAIN OUTCOMES AND MEASURES: For children who underwent
      adenotonsillectomy we determined the length of time from oximetry to surgery,
      postoperative length of stay, postoperative readmissions, and emergency
      department visits in the month following surgery and major surgical
      complications. We analyzed these outcomes by oximetry result. We compared the
      cost savings of our diagnostic approach with those of other diagnostic models.
      RESULTS: Among 362 children, the median age was 4.8 years (interquartile range,
      3.3-6.7), and 61% were male. Two-hundred-sixty-six (73%) and 96 (27%),
      respectively, had inconclusive and abnormal oximetry results. Eighty of 96 of
      children with abnormal oximetry results (83%) and 81 of 266 children with
      inconclusive oximetry results (30%) underwent adenotonsillectomy. Thirty-three of
      266 children (12%) underwent further evaluation with polysomnography; of 14
      diagnosed as having OSA, 12 underwent adenotonsillectomy. Children with abnormal
      oximetry results were operated on soonest after testing and triaged based on
      oximetry results. No child with an inconclusive oximetry result required
      hospitalization for more than 1 night postoperatively; 14% of children (11 of 80)
      with an abnormal oximetry result required hospitalization for 2 or 3 nights (chi2
      = 12.0; P = .001). Rates of readmissions and emergency department visits were
      low, irrespective of oximetry results (whether inconclusive or abnormal). We show
      that our oximetry-based diagnostic approach results in considerable cost savings
      compared with a polysomnography-for-all approach. CONCLUSIONS AND RELEVANCE:
      Oximetry studies evaluated with the McGill Oximetry Score expedite diagnosis and
      treatment of children with adenotonsillar hypertrophy referred for suspected
      sleep-disordered breathing. When resources for testing for sleep-disordered
      breathing are rationed or severely limited, our proposed diagnostic approach can
      help maximize cost-savings and allows sleep laboratories to focus resources on
      medically complex children requiring polysomnographic evaluation of suspected
      sleep disorders.

PMID- 24851856
TI  - Cerebrospinal fluid levels of a 20-22 kDa NH2 fragment of human tau provide a
      novel neuronal injury biomarker in Alzheimer's disease and other dementias.
AB  - Truncation at N-terminal domain of tau protein is early associated with
      neurofibrillary pathology in several human tauopathies, including Alzheimer's
      disease (AD). In affected subjects, the monitoring of total (t-tau) and/or
      phosphorylated tau (p-tau) levels in cerebrospinal fluid (CSF) provides a
      reliable, indirect evaluation of cellular changes occurring in vivo and the
      identification of additional CSF biomarkers would better assist with the clinical
      practice, allowing a broader profile of underlying ongoing neurodegeneration.
      Here we show that a 20-22 kDa NH2-truncated form of human tau (i.e., NH2htau), a
      neurotoxic fragment of the full length protein (htau40) that we previously found
      in synapses from subjects affected by different tauopathies: (i) is not a normal
      constituent of CSF, unlike t-tau and p-tau, being exceptionally detected in
      patients without cognitive impairment; (ii) discriminates, with a weak
      specificity of 65% but a high sensitivity of 85%, patients carrying a large
      spectrum of neurodegenerative diseases associated with cognitive deterioration
      (i.e., AD, frontotemporal lobar degeneration, Parkinson's disease with dementia,
      vascular dementia, mixed dementia, etc.) from subjects affected by other
      neurological disorders without mnesic disability; and (iii) is a neuronal injury
      biomarker as its levels in CSF are not related to the severity and progression of
      cognitive decline. The dynamic evaluation of NH2htau in CSF might add some useful
      hints in the ordinary clinical practice as it provides a novel, general biomarker
      for human tauopathies and other neurodegenerative diseases associated with
      dementia. 

PMID- 24851858
TI  - Relativistic quantum metrology: exploiting relativity to improve quantum
      measurement technologies.
AB  - We present a framework for relativistic quantum metrology that is useful for both
      Earth-based and space-based technologies. Quantum metrology has been so far
      successfully applied to design precision instruments such as clocks and sensors
      which outperform classical devices by exploiting quantum properties. There are
      advanced plans to implement these and other quantum technologies in space, for
      instance Space-QUEST and Space Optical Clock projects intend to implement quantum
      communications and quantum clocks at regimes where relativity starts to kick in.
      However, typical setups do not take into account the effects of relativity on
      quantum properties. To include and exploit these effects, we introduce techniques
      for the application of metrology to quantum field theory. Quantum field theory
      properly incorporates quantum theory and relativity, in particular, at regimes
      where space-based experiments take place. This framework allows for high
      precision estimation of parameters that appear in quantum field theory including
      proper times and accelerations. Indeed, the techniques can be applied to develop
      a novel generation of relativistic quantum technologies for gravimeters, clocks
      and sensors. As an example, we present a high precision device which in principle
      improves the state-of-the-art in quantum accelerometers by exploiting
      relativistic effects. 

PMID- 24851857
TI  - An evidence-based algorithm for the management of marginal ulcers following Roux
      en-Y gastric bypass.
AB  - As the demand for obesity surgery grows, Roux-en-Y gastric bypass remains the
      most commonly performed procedure associated with low complication rates and good
      long-term co-morbidity resolution and weight loss. Marginal ulcers remain a cause
      of significant morbidity in medium and long term and are reported in every large
      series of this operation. Marginal ulceration is a complex problem with unclear
      aetiology and lack of clear consensus on its prevention and management. A clearer
      understanding of the available evidence regarding the prevention and treatment of
      marginal ulcers is needed to improve patient care. We propose an algorithm for
      management of patients with marginal ulcers based on the best available evidence
      in the literature. 

PMID- 24851860
TI  - Synergistic interaction between job control and social support at work on
      depression, burnout, and insomnia among Japanese civil servants.
AB  - PURPOSE: To elucidate whether low job control and low social support at work have
      synergistic interaction on mental health. The synergistic interaction was also
      analyzed after stratification by high and low job demands. METHODS: Participants
      were 2,121 local government employees in Asahikawa city, Japan. The Brief Job
      Stress Questionnaire was used to assess job demands, job control, and social
      support. Depression was assessed using the Patient Health Questionnaire-9. The
      Maslach Burnout Inventory-General Survey was used to assess burnout. Insomnia was
      assessed using the Athens Insomnia Scale. Possible confounder-adjusted logistic
      regression analyses were performed to obtain odds ratios for depression, burnout,
      and insomnia, and synergy indices between job control and social support at work
      were assessed. RESULTS: The synergy indices among men and women, respectively,
      were 2.08 (80 % confidence interval: 1.01, 4.27) and 1.98 (0.67, 5.89) for
      depression, 1.79 (1.28, 2.51) and 2.62 (1.07, 6.40) for burnout, and 1.92 (1.22,
      3.02) and 2.77 (0.43, 18.01) for insomnia. Men with high job demands had higher
      synergistic interaction on depression and burnout, compared to men with low job
      demands, and women with low job demands had higher synergistic interaction
      between job control and social support at work on burnout and insomnia, compared
      to women with high job demands. CONCLUSIONS: There were more-than-additive
      interactions of job control and social support at work on depression, burnout,
      and insomnia. After stratification by job demands, the synergistic interaction
      may be different between men and women. To assess job stress, it is necessary to
      consider the interactive effect of not only job demands and job control but also
      job control and social support at work.

PMID- 24851859
TI  - Identification of a retroelement from the resurrection plant Boea hygrometrica
      that confers osmotic and alkaline tolerance in Arabidopsis thaliana.
AB  - Functional genomic elements, including transposable elements, small RNAs and non
      coding RNAs, are involved in regulation of gene expression in response to plant
      stress. To identify genomic elements that regulate dehydration and alkaline
      tolerance in Boea hygrometrica, a resurrection plant that inhabits drought and
      alkaline Karst areas, a genomic DNA library from B. hygrometrica was constructed
      and subsequently transformed into Arabidopsis using binary bacterial artificial
      chromosome (BIBAC) vectors. Transgenic lines were screened under osmotic and
      alkaline conditions, leading to the identification of Clone L1-4 that conferred
      osmotic and alkaline tolerance. Sequence analyses revealed that L1-4 contained a
      49-kb retroelement fragment from B. hygrometrica, of which only a truncated
      sequence was present in L1-4 transgenic Arabidopsis plants. Additional subcloning
      revealed that activity resided in a 2-kb sequence, designated Osmotic and
      Alkaline Resistance 1 (OAR1). In addition, transgenic Arabidopsis lines carrying
      an OAR1-homologue also showed similar stress tolerance phenotypes. Physiological
      and molecular analyses demonstrated that OAR1-transgenic plants exhibited
      improved photochemical efficiency and membrane integrity and biomarker gene
      expression under both osmotic and alkaline stresses. Short transcripts that
      originated from OAR1 were increased under stress conditions in both B.
      hygrometrica and Arabidopsis carrying OAR1. The relative copy number of OAR1 was
      stable in transgenic Arabidopsis under stress but increased in B. hygrometrica.
      Taken together, our results indicated a potential role of OAR1 element in plant
      tolerance to osmotic and alkaline stresses, and verified the feasibility of the
      BIBAC transformation technique to identify functional genomic elements from
      physiological model species. 

PMID- 24851861
TI  - Targeting S1P receptors in experimental autoimmune encephalomyelitis in mice
      improves early deficits in locomotor activity and increases ultrasonic
      vocalisations.
AB  - Fingolimod (FTY720) is an oral therapy for relapsing remitting multiple sclerosis
      (MS) and targets sphingosine 1-phosphate receptors (S1PRs). FTY720 also rescues
      animals from experimental autoimmune encephalomyelitis (EAE), an animal model of
      MS. The protective effects of FTY720 in EAE are primarily scored manually by
      examining weight loss and limb paralysis that begins around 10-12 days after
      immunisation. To our knowledge, pre-clinical effects of FTY720 on animal
      behaviour early in EAE have not been explored. Here, we developed an automated
      behaviour monitoring system to examine the early effects of FTY720 on subtle pre
      symptomatic behaviour of mice induced with EAE. Our automated home-cage
      monitoring system (AHC-MS) enabled non-contact detection of movement and
      ultrasonic vocalisations (USVs) of mice induced with EAE, thus allowing detection
      of subtle changes in mouse behaviour before paralysis occurs. Mice receiving
      FTY720 emit longer USVs and display higher levels of motor activity than vehicle
      treated EAE mice before clinical symptoms become apparent. Importantly, this
      study promotes the 3Rs ethics (replacement, reduction and refinement) in the EAE
      animal model and may also improve pre-screening of potentially novel MS
      therapies. In addition, this is the first report showing the early effects of
      FTY720 in EAE which underscores its protective effects. 

PMID- 24851862
TI  - The chloroplast genome of Hyoscyamus niger and a phylogenetic study of the tribe
      Hyoscyameae (Solanaceae).
AB  - The tribe Hyoscyameae (Solanaceae) is restricted to Eurasia and includes the
      genera Archihyoscyamus, Anisodus, Atropa, Atropanthe, Hyoscyamus, Physochlaina,
      Przewalskia and Scopolia. Even though the monophyly of Hyoscyameae is strongly
      supported, the relationships of the taxa within the tribe remain unclear.
      Chloroplast markers have been widely used to elucidate plant relationships at low
      taxonomic levels. Identification of variable chloroplast intergenic regions has
      been developed based on comparative genomics of chloroplast genomes, but these
      regions have a narrow phylogenetic utility. In this study, we present the
      chloroplast genome sequence of Hyoscyamus niger and make comparisons to other
      solanaceous plastid genomes in terms of gene order, gene and intron content,
      editing sites, origins of replication, repeats, and hypothetical open reading
      frames. We developed and sequenced three variable plastid markers from eight
      species to elucidate relationships within the tribe Hyoscyameae. The presence of
      a horizontally transferred intron in the mitochondrial cox1 gene of some species
      of the tribe is considered here a likely synapomorphy uniting five genera of the
      Hyoscyameae. Alternatively, the cox1 intron could be a homoplasious character
      acquired twice within the tribe. A homoplasious inversion in the intergenic
      plastid spacer trnC-psbM was recognized as a source of bias and removed from the
      data set used in the phylogenetic analyses. Almost 12 kb of plastid sequence data
      were not sufficient to completely resolve relationships among genera of
      Hyoscyameae but some clades were identified. Two alternative hypotheses of the
      evolution of the genera within the tribe are proposed. 

PMID- 24851863
TI  - An innovative influenza vaccination policy: targeting last season's patients.
AB  - Influenza vaccination is the primary approach to prevent influenza annually.
      WHO/CDC recommendations prioritize vaccinations mainly on the basis of age and co
      morbidities, but have never considered influenza infection history of individuals
      for vaccination targeting. We evaluated such influenza vaccination policies
      through small-world contact networks simulations. Further, to verify our findings
      we analyzed, independently, large-scale empirical data of influenza diagnosis
      from the two largest Health Maintenance Organizations in Israel, together
      covering more than 74% of the Israeli population. These longitudinal individual
      level data include about nine million cases of influenza diagnosed over a decade.
      Through contact network epidemiology simulations, we found that individuals
      previously infected with influenza have a disproportionate probability of being
      highly connected within networks and transmitting to others. Therefore, we showed
      that prioritizing those previously infected for vaccination would be more
      effective than a random vaccination policy in reducing infection. The
      effectiveness of such a policy is robust over a range of epidemiological
      assumptions, including cross-reactivity between influenza strains conferring
      partial protection as high as 55%. Empirically, our analysis of the medical
      records confirms that in every age group, case definition for influenza, clinical
      diagnosis, and year tested, patients infected in the year prior had a
      substantially higher risk of becoming infected in the subsequent year.
      Accordingly, considering individual infection history in targeting and promoting
      influenza vaccination is predicted to be a highly effective supplement to the
      current policy. Our approach can also be generalized for other infectious
      disease, computer viruses, or ecological networks. 

PMID- 24851865
TI  - Adolescents' views about a proposed rewards intervention to promote healthy food
      choice in secondary school canteens.
AB  - Using rewards may be an effective method to positively influence adolescent
      eating behaviour, but evidence regarding this approach is limited. The aim of
      this study was to explore young adolescent views about a proposed reward
      intervention associated with food choice in school canteens. Focus groups were
      held in 10 schools located in lower socioeconomic areas within Northern Ireland
      and involved 90 pupils aged 11-12 years (54 girls, 36 boys). Our findings
      indicated a high degree of acceptability for a reward scheme but there was major
      diversity in the type of rewards valued by pupils, largely defined by
      geographical area and socio-cultural differences. Pupils from rural areas tended
      to emphasize group-based and longer-term rewards, whereas pupils from urban-city
      schools tended to suggest individualistic and immediate rewards. The major
      factors influencing food choice were food price, value for money, taste and
      visual appearance. Pupils felt that factors outside of their control, such as
      being assigned to the second lunch sitting placed considerable constraints on
      their food choice. This research not only indicated a high degree of
      acceptability for a rewards-based intervention but also highlighted a number of
      socio-cultural and environmental factors that should be considered by researchers
      when developing such an intervention. 

PMID- 24851864
TI  - Inactivation of fructose-1,6-bisphosphate aldolase prevents optimal co-catabolism
      of glycolytic and gluconeogenic carbon substrates in Mycobacterium tuberculosis.
AB  - Metabolic pathways used by Mycobacterium tuberculosis (Mtb) to establish and
      maintain infections are important for our understanding of pathogenesis and the
      development of new chemotherapies. To investigate the role of fructose-1,6
      bisphosphate aldolase (FBA), we engineered an Mtb strain in which FBA levels were
      regulated by anhydrotetracycline. Depletion of FBA resulted in clearance of Mtb
      in both the acute and chronic phases of infection in vivo, and loss of viability
      in vitro when cultured on single carbon sources. Consistent with prior reports of
      Mtb's ability to co-catabolize multiple carbon sources, this in vitro
      essentiality could be overcome when cultured on mixtures of glycolytic and
      gluconeogenic carbon sources, enabling generation of an fba knockout (Deltafba).
      In vitro studies of Deltafba however revealed that lack of FBA could only be
      compensated for by a specific balance of glucose and butyrate in which growth and
      metabolism of butyrate were determined by Mtb's ability to co-catabolize glucose.
      These data thus not only evaluate FBA as a potential drug target in both
      replicating and persistent Mtb, but also expand our understanding of the
      multiplicity of in vitro conditions that define the essentiality of Mtb's FBA in
      vivo. 

PMID- 24851866
TI  - The cytoplasmic tail of FPC antagonizes the full-length protein in the regulation
      of mTOR pathway.
AB  - FPC (fibrocystin or polyductin) is a single transmembrane receptor-like protein,
      responsible for the human autosomal recessive polycystic kidney disease (ARPKD).
      It was recently proposed that FPC undergoes a Notch-like cleavage and
      subsequently the cleaved carboxy(C)-terminal fragment translocates to the
      nucleus. To study the functions of the isolated C-tail, we expressed the
      intracellular domain of human FPC (hICD) in renal epithelial cells. By 3
      dimensional (3D) tubulogenesis assay, we found that in contrast to tubule-like
      structures formed from control cells, hICD-expressing cells exclusively formed
      cyst-like structures. By western blotting, we showed that the Akt/mTOR pathway,
      indicated by increased phosphorylation of Akt at serine 473 and S6 kinase 1 at
      threonine 389, was constitutively activated in hICD-expressing cells, similar to
      that in FPC knockdown cells and ARPKD kidneys. Moreover, application of mTOR
      inhibitor rapamycin reduced the size of the cyst-like structures formed by hICD
      expressing cells. Application of either LY294002 or wortmannin inhibited the
      activation of both S6K1 and Akt. Expression of full-length FPC inhibited the
      activation of S6 and S6 kinase whereas co-expression of hICD with full-length FPC
      antagonized the inhibitory effect of full-length FPC on mTOR. Taken together, we
      propose that FPC modulates the PI3K/Akt/mTOR pathway and the cleaved C-tail
      regulates the function of the full-length protein. 

PMID- 24851867
TI  - Helminth colonization is associated with increased diversity of the gut
      microbiota.
AB  - Soil-transmitted helminths colonize more than 1.5 billion people worldwide, yet
      little is known about how they interact with bacterial communities in the gut
      microbiota. Differences in the gut microbiota between individuals living in
      developed and developing countries may be partly due to the presence of
      helminths, since they predominantly infect individuals from developing countries,
      such as the indigenous communities in Malaysia we examine in this work. We
      compared the composition and diversity of bacterial communities from the fecal
      microbiota of 51 people from two villages in Malaysia, of which 36 (70.6%) were
      infected by helminths. The 16S rRNA V4 region was sequenced at an average of
      nineteen thousand sequences per samples. Helminth-colonized individuals had
      greater species richness and number of observed OTUs with enrichment of
      Paraprevotellaceae, especially with Trichuris infection. We developed a new
      approach of combining centered log-ratio (clr) transformation for OTU relative
      abundances with sparse Partial Least Squares Discriminant Analysis (sPLS-DA) to
      enable more robust predictions of OTU interrelationships. These results suggest
      that helminths may have an impact on the diversity, bacterial community structure
      and function of the gut microbiota. 

PMID- 24851868
TI  - Screening for autism spectrum disorders with the brief infant-toddler social and
      emotional assessment.
AB  - OBJECTIVE: Using parent-completed questionnaires in (preventive) child health
      care can facilitate the early detection of psychosocial problems and
      psychopathology, including autism spectrum disorders (ASD). A promising
      questionnaire for this purpose is the Brief Infant-Toddler Social and Emotional
      Assessment (BITSEA). The screening accuracy with regard to ASD of the BITSEA
      Problem and Competence scales and a newly calculated Autism score were evaluated.
      METHOD: Data, that was collected between April 2010 and April 2011, from a
      community sample of 2-year-olds (N = 3127), was combined with a sample of
      preschool children diagnosed with ASD (N = 159). For the total population and for
      subgroups by child's gender, area under the Receiver Operating Characteristic
      (ROC) curve was examined, and across a range of BITSEA Problem, Competence and
      Autism scores, sensitivity, specificity, positive and negative likelihood
      ratio's, diagnostic odds ratio and Youden's index were reported. RESULTS: The
      area under the ROC curve (95% confidence interval, [95%CI]) of the Problem scale
      was 0.90(0.87-0.92), of the Competence scale 0.93(0.91-0.95), and of the Autism
      score 0.95(0.93-0.97). For the total population, the screening accuracy of the
      Autism score was significantly better, compared to the Problem scale. The
      screening accuracy of the Competence scale was significantly better for girls
      (AUC = 0.97; 95%CI = 0.95-0.98) than for boys (AUC = 0.91; 95%CI = 0.88-0.94).
      CONCLUSION: The results indicate that the BITSEA scales and newly calculated
      Autism score have good discriminative power to differentiate children with and
      without ASD. Therefore, the BITSEA may be helpful in the early detection of ASD,
      which could have beneficial effects on the child's development.

PMID- 24851869
TI  - Exaggerated blood pressure variability in patients with pneumoconiosis: a pilot
      study.
AB  - BACKGROUND: Chronic hypoxia is a risk factor for cardiovascular disease, but its
      association with blood pressure (BP) remains unclear. We performed this study to
      clarify the hypothesis that chronic hypoxia is associated with abnormal BP
      variability in patients with pneumoconiosis. METHODS: We recruited 19 patients
      with pneumoconiosis and 30 age- and BP level-matched control subjects. We used
      simultaneous pulse oximetry and ambulatory BP monitoring for all subjects. We
      evaluated their BP levels and variability by determining the SD and coefficient
      of variation (CV) of the BP data. The dipper pattern was defined as nocturnal BP
      fall >=10%; the nondipper pattern was defined as nocturnal BP fall >=0% but <10%;
      the riser pattern was defined as nocturnal BP fall <0%. Pearson and Spearman
      correlation coefficients were used to calculate the correlations between
      parameters. RESULTS: In patients with pneumoconiosis, the daytime systolic BP
      (SBP) level was lower, the CV in 24-hour SBP (P < 0.05) and diastolic BP (P <
      0.001) were higher than that in control subjects. And although not statistically
      significant (P = 0.13), the odds ratio of riser pattern was 3.73 in patients with
      pneumoconiosis, and their nighttime pulse rate was significantly higher (P <
      0.05) than that in control subjects. The median daytime pulse oximetry oxygen
      saturation was inversely associated with mean (r = -0.30; P < 0.01) and SD (r = 
      0.38; P < 0.001) in daytime SBP. The median nighttime pulse oximetry oxygen
      saturation was inversely associated (r = -0.55; P < 0.001) and the mean nighttime
      pulse rate was associated (r = 0.51; P < 0.001) with CV in nighttime SBP. Partial
      pressure of oxygen was inversely associated with CV in daytime SBP (r = -0.24; P
      < 0.05). CONCLUSIONS: Exaggerated BP variability was seen in patients with
      pneumoconiosis, and the measures of hypoxia were associated with large
      fluctuations in ambulatory BP. Chronic and intermittent hypoxia could be the
      contributing factors of these findings. CLINICAL TRIAL REGISTRATION: Clinical
      Trial Number UMIN000000894 (University Hospital Medical Information Network
      Clinical Trials Registry website).

PMID- 24851871
TI  - Dementia strategy should focus on reducing risks and promoting brain health, say
      experts.

PMID- 24851872
TI  - Needs assessments of memory disorder patients.
AB  - BACKGROUND: Previous research shows that informal caregivers of individuals with
      a memory disorder experience financial strain, declining physical health, and
      psychological distress. Various resources and services have been developed to
      address and/or prevent these potential outcomes, yet caregivers continue to be
      negatively affected by the demands of caregiving. We hypothesize that better
      identification and clarification of concrete patient and caregiver needs will aid
      in the modification and improvement of the available resources. The purpose of
      this study is to determine the psychosocial needs of the cognitively impaired
      population and their caregivers. METHODS: A one-page Needs Assessment was created
      to address areas of potential concern for the individual with a memory disorder
      and the caregiver. This assessment was administered during visits to an
      outpatient clinic in Philadelphia. RESULTS: A total of 204 Needs Assessments were
      collected. The significant needs found in our study cohort include sleep,
      exercise, clinical trials, education, and assistance with ADLs and IADLs.
      CONCLUSIONS: This study satisfied the initial identification of caregiver and
      patient needs; now each must be explored further to determine how to successfully
      meet such needs. If the primary needs of the patient can be met by a focused
      service, the caregiver will no longer be the sole provider of meeting the
      specific need. This will decrease the involved role of the caregiver, maximize
      patient homecare, minimize caregiver stress, and increase the quality of life for
      both the patient and caregiver.

PMID- 24851873
TI  - Beyond reminiscence: using generic video to elicit conversational language.
AB  - Videos and multimedia are increasingly used to stimulate reminiscence in dementia
      care. However, they are also valuable in eliciting a wide range of language
      patterns that are not necessarily keyed to reminiscence about self. Low
      technology, home-made generic and personalized videos were tested with 2 samples
      of persons with dementia, to increase engagement and support the retention of
      identity. Participants showed a slight, though not significant, preference for
      looking first at personalized videos and produced a wider range of conversational
      language topics and phrasal patterns in response to the generic videos. 

PMID- 24851875
TI  - Lifelong rupture risk of intracranial aneurysms depends on risk factors: a
      prospective Finnish cohort study.
AB  - BACKGROUND AND PURPOSE: Our aim was to define for the first time the lifelong
      natural course of unruptured intracranial aneurysms (UIAs) and identify high-risk
      and low-risk patients for the rupture. METHODS: One hundred and eighteen patients
      (61 women) with UIAs were diagnosed between 1956 and 1978 and followed up until
      death or subarachnoid hemorrhage (SAH). The median age at the diagnosis was 43.5
      years (range, 22.6-60.7 years). The median size of the UIA at the diagnosis was 4
      mm (range, 2-25 mm). Analyzed risk factors for a rupture included sex, age,
      cigarette smoking, systolic blood pressure values, diagnosed hypertension, UIA
      size, and number of UIAs. RESULTS: Thirty four (29%) out of 118 people had SAH
      during the lifelong follow-up. The median age at SAH was 51.3 years (range, 30.1
      71.8 years). The annual rupture rate per patient was 1.6%. Female sex, current
      smoking, and aneurysm size of >=7 mm in diameter were risk factors for a lifetime
      SAH. Depending on the risk factor burden, the lifetime risk of an aneurysmal SAH
      varied from 0% to 100%, and the annual rupture rate from 0% to 6.5%. Of the 96
      patients with small (<7 mm) UIAs, 24 (25%) had an aneurysmal SAH during the
      follow-up. CONCLUSIONS: Almost 30% of all UIAs in people of working age ruptured
      during a lifelong follow-up. The risk varied substantially on the basis of risk
      factor burden. Because even small UIAs ruptured, treatment decisions of UIAs
      should perhaps be based on the risk factor status.

PMID- 24851870
TI  - The complex ultrastructure of the endolysosomal system.
AB  - Live-cell imaging reveals the endolysosomal system as a complex and highly
      dynamic network of interacting compartments. Distinct types of endosomes are
      discerned by kinetic, molecular, and morphological criteria. Although none of
      these criteria, or combinations thereof, can capture the full complexity of the
      endolysosomal system, they are extremely useful for experimental purposes. Some
      membrane domain specializations and specific morphological characteristics can
      only be seen by ultrastructural analysis after preparation for electron
      microscopy (EM). Immuno-EM allows a further discrimination of seemingly identical
      compartments by their molecular makeup. In this review we provide an overview of
      the ultrastructural characteristics and membrane organization of endosomal
      compartments, along with their organizing machineries. 

PMID- 24851874
TI  - Capillary Index Score in the Interventional Management of Stroke trials I and II.
AB  - BACKGROUND AND PURPOSE: The Capillary Index Score (CIS) is a simple angiography
      based scale for assessing viable tissue in the ischemic territory. We
      retrospectively applied it to Interventional Management of Stroke (IMS) trials I
      and II to evaluate the predictive value for good outcomes. METHODS: CIS was
      calculated from pretreatment diagnostic cerebral angiograms blinded to outcome.
      IMS I and II diagnostic cerebral angiogram images of sufficient quality were
      reviewed and CIS calculated for treated subjects with internal carotid artery or
      M1 occlusion. CIS scoring (0-3) was dichotomized into favorable (f CIS; 2 or 3)
      and poor (p CIS; 0 or 1). Modified thrombolysis in cerebral infarction score 2b
      or 3 was considered good revascularization. CIS and modified thrombolysis in
      cerebral infarction scores were compared with good outcome, defined as modified
      Rankin Scale score<=2 at 90 days. RESULTS: Twenty-eight of 161 subjects met the
      inclusion criteria. Thirteen (46%) had f CIS. Good clinical outcome was
      significantly different between the 2 CIS groups (62% for f CIS versus 7% for p
      CIS; P=0.004). Good reperfusion correlated to good outcome (P=0.04). No
      significant differences in time to intravenous or intra-arterial treatment were
      identified between f CIS and p CIS groups (P>0.25). CONCLUSIONS: A f CIS was
      found in ~50% of subjects and was a virtual prerequisite for good outcome in this
      study subgroup of IMS I and II. We call this the 50% barrier.

PMID- 24851876
TI  - A DTX/MATE-type transporter facilitates abscisic acid efflux and modulates ABA
      sensitivity and drought tolerance in Arabidopsis.
AB  - Abscisic acid (ABA) regulates numerous physiological and developmental processes
      in plants. Recent studies identify intracellular ABA receptors, implicating the
      transport of ABA across cell membranes as crucial for ABA sensing and response.
      Here, we report that a DTX/Multidrug and Toxic Compound Extrusion (MATE) family
      member in Arabidopsis thaliana, AtDTX50, functions as an ABA efflux transporter.
      When expressed heterologously in both an Escherichia coli strain and Xenopus
      oocyte cells, AtDTX50 was found to facilitate ABA efflux. Furthermore, dtx50
      mutant mesophyll cells preloaded with ABA released less ABA compared with the
      wild-type (WT). The AtDTX50 gene was expressed mainly in the vascular tissues and
      guard cells and its expression was strongly up-regulated by exogenous ABA. The
      AtDTX50::GFP fusion protein was localized predominantly to the plasma membrane.
      The dtx50 mutant plants were observed to be more sensitive to ABA in growth
      inhibition. In addition, compared with the WT, dtx50 mutant plants were more
      tolerant to drought with lower stomatal conductance, consistent with its function
      as an ABA efflux carrier in guard cells. 

PMID- 24851877
TI  - Nanoparticle-delivered quercetin for cancer therapy.
AB  - Quercetin, a natural protective bioflavonoid, possesses diverse pharmacologic
      effects, such as antioxidant, anti-inflammatory, anti-proliferative, and anti
      angiogenic activities. Recently, quercetin's effect in cancer prevention and
      treatment was recognized. However, the poor water solubility and low
      bioavailability of quercetin limit its clinical use in cancer therapy.
      Nanotechnology provides a method to create novel formulations for hydrophobic
      drug. Nanoparticles-delivered quercetin has attracted many attentions for its
      enhanced anticancer potential and promising clinical application. This review
      will discuss the application of nanotechnology in quercetin delivery for cancer
      therapy.

PMID- 24851879
TI  - The effect of lycopene on the PI3K/Akt signalling pathway in prostate cancer.
AB  - Prostate cancer is common in men with very high mortality which is one of leading
      causes of cancer-related deaths in men. The main treatment approaches for
      metastasized prostate cancer are androgen deprivation and chemotherapeutic
      agents. Although there are initial responses to castration, the resistance to the
      treatment will eventually occur, leading to castration-resistant prostate cancer.
      The common chemotherapeutic agents for the treatment of prostate cancer are
      docetaxel and taxane but outcomes of using these drugs have not been
      satisfactory. Therefore, it is necessary to find better treatment approaches for
      prostate cancer and to search for compounds that are effective in prostate cancer
      prevention. Lycopene extracted from tomato and other fruits or plants such as
      Gac, watermelon, pink grapefruit, pink guava, red carrot and papaya has been
      shown to be effective on prostate cancer prevention and treatment. The advantage
      of the application of lycopene for its anti-prostate cancer activity is that
      lycopene can reach much higher concentration in prostate tissue than other
      tissues. In this review, the effect of lycopene on PI3K/Akt pathway is
      summarised, which could be one of major mechanisms for anti-cancer activity of
      lycopene.

PMID- 24851878
TI  - From French Paradox to cancer treatment: anti-cancer activities and mechanisms of
      resveratrol.
AB  - Resveratrol (3, 5, 4'-trihydroxy-trans-stilbene, RVT), a stilbenoid, polyphenol
      phytochemical present in berries, grape, peanuts and wine. It has been suggested
      as a major contributor to "French Paradox" that reduces the mortality from
      coronary heart disease (CHD) by consuming RVT in red wine even in some of French
      population with a high-fat intake. With extensive research, it has been found
      that RVT is a versatile and pleiotropic agent, it not only possesses
      cardiovascular-protective benefits by its powerful antioxidant capacity, anti
      inflammatory, regulating metabolism and anti-aging effects, but also has strong
      anti-tumor activities through inhibiting tumor cell proliferation, inducing cell
      apoptosis, promoting tumor cell differentiation, preventing tumor invasion and
      metastasis, and further moderating the host immune system to kill tumor cells.
      This review will focus on RVT's anti-tumor activity and tumor prevention
      potential including: the anti-tumor spectrum in vitro and in vivo; molecular
      targets and signal pathways involving RVT anti-tumor mechanisms; evidences from
      clinical trial for its bioavailability, dosage, toxicity and benefit in humans;
      and its prospective including its analog, deviations, and combinative
      chemotherapy.

PMID- 24851880
TI  - Garlic-derived allyl sulfides in cancer therapy.
AB  - Garlic (Allium sativam L.) is widely used in traditional herbal remedies and
      alternative medicine. The potential health benefits of garlic are largely
      attributed to its metabolic byproducts. Extensive in vivo and in vitro studies
      has demonstrated that the garlic derivatives possess anti-cancer effects, but the
      underlying mechanisms are not completely understood. In this mini-review, we aim
      to summarize the reported biological effects of garlic products as anti-tumor
      agents, and present the possible molecular mechanisms responsible for the anti
      carcinogenesis effects of garlic and its derivatives.

PMID- 24851881
TI  - Curcumin: a promising agent targeting cancer stem cells.
AB  - Cancer stem cells are a subset of cells that are responsible for cancer
      initiation and relapse. They are generally resistant to the current anticancer
      agents. Successful anticancer therapy must consist of approaches that can target
      not only the differentiated cancer cells, but also cancer stem cells. Emerging
      evidence suggested that the dietary agent curcumin exerted its anti-cancer
      activities via targeting cancer stem cells of various origins such as those of
      colorectal cancer, pancreatic cancer, breast cancer, brain cancer, and head and
      neck cancer. In order to enhance the therapeutic potential of curcumin, this
      agent has been modified or used in combination with other agents in the
      experimental therapy for many cancers. In this mini-review, we discussed the
      effect of curcumin and its derivatives in eliminating cancer stem cells and the
      possible underlying mechanisms.

PMID- 24851882
TI  - Novel mechanisms of anticancer activities of green tea component epigallocatechin
      3-gallate.
AB  - After water, tea is the most widely consumed beverage. The major active
      constituents in green tea are catechins, of which epigallocatechin-3-gallate
      (EGCG) is the most abundant and active compound. Animal experimental studies
      using EGCG alone or green tea catechins with EGCG being a major component have
      generated a mounting body of evidence suggesting that EGCG as a naturally
      occurring compound and commonly consumed beverage ingredient is a promising
      cancer preventive agent. However, the relationship between green tea consumption
      and reduced cancer risk seen from epidemiologic studies is not as encouraging as
      that observed in animal studies and remains inconclusive. In the present article,
      the achievements using EGCG or green tea catechins for cancer prevention were
      reviewed, the latest identified anticancer mechanisms of EGCG and the emerging
      mechanism-based cancer therapies of EGCG were outlined, and the potential reasons
      for the discrepancy in animal studies and epidemiological studies were
      tentatively analysed. On the basis of these analyses, it could be anticipated
      that future intervention trials in humans would be able to achieve consistent
      cancer prevention effects provided that the timely intervention of EGCG or green
      tea catechins at appropriate high-dose levels presumably approaching their upper
      safety limits have had been fully considered.

PMID- 24851883
TI  - [Progression in predicting high-risk prostate cancer using tissue biomarkers].

PMID- 24851884
TI  - [Effects of bladder neck preservation and reconstruction of rhabdosphincter on
      urinary continence recovery after laparoscopic radical prostatectomy].
AB  - OBJECTIVE: To retrospectively analyze the effects of bladder neck preservation
      (BNP) and reconstruction of rhabdosphincter (RS) on urinary continence recovery
      for patients after laparoscopic radical prostatectomy (LRP). METHODS: Bladder
      neck preservation plus reconstruction of rhabdosphincter (BNP+RS) was employed in
      18 prostate cancer patients after LRP from January 2011 to December 2012.
      Eighteen contemporary cases of routine LRP were selected for control group. The
      operative duration, blood loss volume, postoperative surgical margins, urine
      leakage and continence rate were compared between two groups. RESULTS: LRP was
      successfully performed through extraperitoneal space in all 36 cases. There was
      no conversion into open surgery. The median operative duration, blood loss
      volume, positive surgical margins and urine leakage rate in BNP+RS and control
      groups were 164 (125-245) versus 142 (95-210) min, 195 (80-550) versus 230 (120
      400) ml, 3 versus 2 cases and 0 versus 2 cases respectively. At 3, 6, 12 months,
      the continence rates in BNP+RS and control groups were 12 cases (66.7%) versus 5
      cases (13.9%, P = 0.044) , 15 cases(83.3%) versus 11 cases (30.6%, P = 0.264) and
      16 cases (88.9%) versus 13 cases (36.1%, P = 0.402) respectively. A significant
      higher continence rate in the first 3 months postoperatively was found in BNP+RS
      group than control group. CONCLUSION: BNP plus RS reconstruction after LRP can
      significantly improve continence in the first 3 months after operation.

PMID- 24851885
TI  - [Clinical significance of serum telomerase mRNA in patients with prostate
      cancer].
AB  - OBJECTIVE: To explore the clinical significance of detecting serum mRNA of
      telomerase in the diagnosis of prostate cancer. METHODS: Serum samples were
      collected from 29 patients with prostate cancer and 29 age-matched patients with
      cardiovascular or metabolic disease as non-tumor controls. Sera samples from 15
      healthy age-matched subjects were used as healthy control. Detection of serum
      telomerase mRNA was performed with real-time reverse transcriptase quantitative
      polymerase chain reaction (PCR). RESULTS: Serum telomerase mRNA was detectable in
      89.7% (26/29) patients with prostate cancer, but almost undetectable in non-tumor
      (6.9%, 2/29) and healthy control groups(1/14). CONCLUSION: Using real-time PCR
      for detecting serum telomerase mRNA may be an auxiliary method for diagnosing and
      monitoring of prostate cancer.

PMID- 24851886
TI  - [Value of magnetic resonance imaging for early diagnosis of prostatic carcinoma
      in central zone].
AB  - OBJECTIVE: To explore the magnetic resonance imaging (MRI) manifestations of
      early prostatic carcinoma (PCa) in central zone (CZ) . METHODS: A total of 284
      cases of PCa were scanned by MRI while 24 cases of carcinoma in 28 PCa focus were
      in central zone. Their T1WI, T2WI, DWI and ADC value characteristics were
      analyzed respectively and the completeness of annular low signal between central
      and peripheral zones were observed. At the same time, 45 cases of PCa were
      located in peripheral zone (PZ) . Twenty cases of benign prostatic hyperplasia
      (BPH) were comparatively analyzed. All cases received a histological diagnosis.
      RESULTS: Most cases of early PCa in CZ demonstrated ill-defined margin, amorphous
      shape and equal signal intensity on T1WI, low signal intensity on T2WI and high
      signal intensity on DWI. The mean ADC value for PCa focus was (0.867 +/-
      0.074)*10(-3) mm(2)/s and PCa foci were enhanced slightly. In these cases, most
      annular low signals between CZ and PZ were destroyed. The difference of ADC
      values between PCa in CZ and PZ groups ((0.914 +/- 0.066) *10(-3) mm(2)/s ) had
      no statistic significance (P > 0.05) , but the ADC values between PCa and BPH in
      CZ groups ((1.517 +/- 0.315) *10(-3) mm(2)/s ) had statistically significant
      difference (P < 0.05). CONCLUSION: Some reliable diagnostic characteristics on
      MRI may be used for an early diagnosis of PCa in CZ.

PMID- 24851887
TI  - [Correlation of thyroid-stimulating hormone with metabolic syndrome in euthyroid
      male elders].
AB  - OBJECTIVE: To explore the relationship between thyroid-stimulating hormone (TSH)
      and metabolic syndrome (MS) and its components in euthyroid male elders. METHODS:
      For this cross-sectional study, 307 euthyroid male elders aged over 60 years
      participating in a routine annual health screening examination at our hospital
      during May-June 2011 were enrolled. Their mean age was (72.6 +/- 7.9) years.
      Height, weight, blood pressure, blood glucose, blood lipids, fasting insulin
      levels and thyroid functions (TT3, TT4, FT3, FT4, TSH, TgAb & TPOAb) were
      measured. And the association of thyroid functions and the presence of MS and its
      components was analyzed. RESULTS: The prevalence of MS was 40.7% (125/307). The
      TSH level was significantly higher in the MS and obese group than that in control
      group ((2.6 +/- 1.1) vs (2.4 +/- 1.0) mU/L, P = 0.014; (2.7 +/- 1.1) vs (2.3 +/-
      1.1)mU/L, P = 0.007). The prevalence of MS and obesity showed a gradual increase
      according to the TSH tertiles. When comparing subjects in the highest and lowest
      tertile of TSH, the former group demonstrated 1.872 and 1.904-fold increases in
      the odds ratio for obesity and MS after adjusting for age and homeostasis model
      assessment for insulin resistance (HOMA-IR) (95%CI: 1.051-3.332, P = 0.033;
      95%CI: 1.070-3.387, P = 0.028) . Logistic regression analysis showed that the TSH
      levels were independent influencing factors for MS in male elders (OR = 1.324,
      95%CI:1.042-1.683) . CONCLUSION: High circulating TSH level, albeit normal, is
      associated with elevated risk for metabolic syndrome in male elders.

PMID- 24851888
TI  - [Associations of ulcerative colitis with vitamin D receptor gene polymorphisms
      and serum levels of 25-hydroxyl vitamin D].
AB  - OBJECTIVE: To explore the associations of ulcerative colitis (UC) with vitamin D
      receptor (VDR) gene polymorphisms and serum levels of 25-hydroxyl vitamin
      D[25(OH)D]. METHODS: From July 2004 to July 2013, a total of 404 UC patients were
      recruited from 4 hospitals of Wenzhou City. A total of 612 controls were
      collected from Health Examination Center of Second Affiliated Hospital of Wenzhou
      Medical University. Four single nucleotide polymorphisms of VDR (Fok I, Bsm I,
      Apa I, Taq I) were detected by mini-sequencing technique. The frequencies of
      minor allele and genotype of VDR were compared between UC patients and the
      controls by chi(2) test and Bonferroni correction. Moreover, 75 UC patients and
      120 gender-and age-matched healthy controls during the corresponding period were
      randomly selected for determining the serum levels of 25(OH)D by
      electrochemiluminescence immunoassay and were compared by Student's test.
      RESULTS: After Bonferroni correction, mutant allele and genotype frequencies of
      VDR (Fok I, Bsm I, Apa I, Taq I) did not statistically differ between UC patients
      and the controls (all P > 0.012 5). Stratification by the Truelove & Witts
      severity index, mutant allele (C) and genotype (TC+CC) of VDR(Fok I) were
      significantly higher in patients with mild and moderate UC than in those with
      severe UC (54.37% (373/686) vs 37.70% (46/122), 81.92% (281/343) vs 55.74%
      (34/61), both P < 0.01). Haplotype analysis showed that three polymorphic loci of
      Bsm I, Apa Iand Taq Iwere in a complete linkage disequilibrium. The AAC haplotype
      decreased significantly in UC patients compared to the controls (3.58% (29/808)
      vs 6.01% (74/1 224), P = 0.012). The average serum levels of 25 (OH)D in UC
      patients were significantly lower than those in the controls ((48 +/- 17) vs (54
      +/- 18)nmol/L, P = 0.017). Furthermore, the average serum levels of 25(OH)D were
      significantly higher in patients with mild and moderate UC than in those with
      severe UC and were significantly lower in patients with extensive colitis than in
      those with distal colitis (both P < 0.01). By linear regression analysis, the
      serum levels of 25(OH)D in UC patients were independently and positively
      correlated with hemoglobin (beta = 0.499, P < 0.01) and yet independently and
      negatively correlated with C-reaction protein (beta = -0.346, P < 0.01) and white
      blood cells (beta = -0.291, P = 0.002). Using Logistic regression analysis, it
      was found that mutant genotype (GA/AA) of VDR (Bsm I) played an independently
      protective role in UC (OR = 0.328, P = 0.028) while mutant genotype (TC/CC) of
      VDR (Fok I) and vitamin D deficiency (<50.0 nmol/L) had an interaction in UC (OR
      = 2.070, P = 0.006). CONCLUSIONS: Genetic polymorphism of VDR (Fok I, Bsm I, Apa
      I, Taq I) and serum levels of 25(OH)D are significantly correlated with UC.
      Mutation of VDR (Bsm I) is a protective factor for UC. Moreover, mutant genotype
      (TC/CC) of VDR (Fok I) and vitamin D deficiency may exert synergistic effects on
      the susceptibility to UC.

PMID- 24851889
TI  - [Correlation between the expression of neuropilin-2 and tumor-associated
      lymphangiogenesis in gastric cancer and clinicopathological parameters].
AB  - OBJECTIVE: To explore the correlation between the expression of neuropilin-2
      (NRP2) and tumor-associated lymphangiogenesis and clinicopathological parameters
      in gastric carcinoma (GC). METHODS: All GC, margin and normal tissues of 65 cases
      through surgical resection were retrospectively collected at our hospital and
      Tangshan People's Hospital from October 2011 to October 2013. The expressions of
      NRP2 in GC, tumor margin and normal gastric tissues were analyzed by
      immunohistochemistry. Lymphangiogenesis was marked with D2-40 monoclonal antibody
      and microlymphatic density (MLD) counted. And the morphology of lymphatic vessels
      was observed. RESULTS: A positive expression of NRP2 was found in GC (n = 40,
      61.5%) and it was significantly higher than that in tumor margin (n = 32, 49.2%)
      and normal tissues (n = 3, 4.6%) (P < 0.05). But the counts of MLD in both GC (12
      +/- 5)/mm(2) and normal region (23 +/- 6)/mm(2) were significantly lower than
      that of tumor margin region (44 +/- 13)/mm(2) (P < 0.05). In addition, the
      morphologies of lymphatic vessels were different among 3 groups. Also NRP2
      expression and MLD count were correlated with differentiation degree,
      infiltrative degree, lymphatic vessel invasion, lymph node metastasis and TNM
      staging of GC (all P < 0.05). The expression intensity of NRP2 in tumor margin
      tissues was positively correlated with MLD (r = 0.517, P = 0.000). CONCLUSIONS:
      The expression of NRP2 in GC may modulate lymphangiogenesis and lymphatic
      metastasis. And it may play a key role in tumorigenesis, progression and
      prognosis predicating in GC.

PMID- 24851890
TI  - [Plasma DNA methylation of shp1 in patients with diffuse large B cell lymphoma].
AB  - OBJECTIVE: To explore the methylation status of shp1 gene in plasma DNA from
      patients with diffuse large B cell lymphoma (DLBCL) and discuss its possible
      application in molecular diagnosis and targeted therapy of the disease. METHODS:
      Methylation-specific polymerase chain reaction (MSP) was used to detect the
      methylation status of shp1 gene in plasma and peripheral blood leukocytes (PBLs)
      of 35 DLBCL patients. The formaldehyde-fixed, paraffin-embedded (FFPE) tumor
      tissue samples were collected from 28 DLBCL patients, 6 patients of benign
      lymphoid hyperplasia and 13 healthy volunteers were selected as nonmalignant
      controls from January 2012 to December 2013. Methylation frequencies of shp1 gene
      in different groups were compared and the associations of shp1 methylation status
      with clinicopathological characteristics were analyzed. RESULTS: No methylation
      of shp1 was detected in any of the 19 nonmalignant controls. The methylation rate
      of shp1 in plasma, PBLs and FFPE tumor tissues from patients with DLBCL was 51.4%
      (18/35), 28.6% (10/35) and 64.3% (18/28) respectively; there was a high
      methylation consistency of shp1 between plasma and FFPE tumor tissues (kappa =
      0.78, P = 0.00).However, methylation consistency was lower between PBLs and FFPE
      tumor tissues (kappa = 0.36, P = 0.01). Methylation of shp1 was frequently
      detected in plasma and FFPE tumor tissues samples from patients with a high serum
      level of lactate dehydrogenase (13/16 vs 5/19, 11/12 vs 7/16, P = 0.02, 0.04)
      .However, no such association was detected in PBLs (P = 0.14). CONCLUSIONS:
      Methylation of shp1 in plasma DNA can represent shp1 methylation status in tumor
      tissue. And it may serve as a promising biomarker in aiding DLBCL diagnosis and
      guiding targeted therapy.

PMID- 24851891
TI  - [Value of cardiopulmonary exercise test in cardiac function evaluation of
      patients with chronic left heart failure caused by dilated cardiomyopathy].
AB  - OBJECTIVE: To assess the value of cardiopulmonary exercise test in the evaluation
      of cardiac function in patients with chronic left heart failure caused by dilated
      cardiomyopathy. METHODS: Fifty-three inpatients aged 18 year and over with
      chronic left heart failure caused by dilated cardiomyopathy at Fuwai Hospital
      from October 2010 to October 2011 were selected and divided into 2 groups
      according to the New York Heart Association (NYHA) heart function classification.
      One group had 20 cases for class II and another 33 cases for class III-IV. All of
      them received cardiopulmonary exercise tests. Synchronous measurement and record
      of gas exchange indices were taken during every breath, and so were heart rate,
      blood pressure, electrocardiogram and blood oxygen saturation. At the same time,
      other routine tests were also performed. After exercise test, anaerobic threshold
      and peak oxygen consumption indices were calculated and statistically analyzed.
      They also received subsequent follow-ups of 1 day, 1 week, 1 month, 6 months and
      1 year, including activities, clinical manifestations and cardiac adverse events.
      RESULTS: At baseline, the differences in gender, age, body mass index, concurrent
      diseases, left ventricular end-diastolic diameter, left ventricular ejection
      fraction and serum creatinine had no statistical significance (P > 0.05).
      Compared with cardiac function class II group, the class III-IV group had higher
      left atrial diameter, level of amino terminal pro-B-type natriuretic peptide (NT
      proBNP), incidence of atrial fibrillation ((51.4 +/- 7.5) vs (43.6 +/- 7.7) mm,
      (2 607 +/- 1 782) vs (1 312 +/- 901) ug/L, 42.4% (14/33) vs 5.0% (1/20)) and
      lower glomerular filtration rate, peak oxygen consumption, levels of anaerobic
      threshold ((72 +/- 20) vs (97 +/- 23) ml/min, (13.7 +/- 2.6) vs (20.5 +/- 3.6)
      ml.min(-1).kg(-1), (10.7 +/- 1.5) vs (13.3 +/- 2.1) ml.min(-1).kg(-1)) (all P <
      0.01). And NT-proBNP and cardiac function classification showed a positive
      correlation (OR = 1.002, P = 0.003) while peak oxygen consumption, anaerobic
      threshold and cardiac function classification were negatively correlated (OR =
      0.736, 0.608; P = 0.011, 0.001). CONCLUSIONS: Cardiopulmonary exercise test
      objectively reflects the cardiopulmonary reserve of heart failure patients with
      dilated cardiomyopathy. And the parameters of anaerobic threshold and peak oxygen
      consumption may reflect the patient's motor ability quantitatively and
      accurately.

PMID- 24851892
TI  - [Imaging evaluations of Salter innominate osteotomy for developmental dysplasia
      of the hip].
AB  - OBJECTIVE: To evaluate the imaging efficacies after Salter innominate osteotomy
      for developmental dysplasia of the hip (DDH). METHODS: A total of 51 DDH patients
      with 70 hips were recruited between March 2011 to August 2012. All of them
      underwent Salter innominate osteotomy. Preoperative radiographs including
      acetabular index (AI), sharp angle (SA), obturator angle and obturator height
      were measured. And postoperative radiographs were taken at 2 days, 3 months, 6
      months and 1 year to measure the parameters of AI, sharp acetabular angle,
      obturator angle, obturator height, shifting index and descending angle of distal
      iliac end. Paired t test was used for statistical analyses. RESULTS: The average
      correction of AI was 35.5 degrees  +/- 2.3 degrees  preoperatively versus 14.6
      degrees  +/- 1.6 degrees  postoperatively ( P = 0.000) . The average correction
      of Sharp angle was 50.6 degrees  +/- 3.7 degrees  preoperatively versus 33.1
      degrees  +/- 3.2 degrees  postoperatively (P = 0.000) . The average correction of
      obturator angle was 58.3 degrees  +/- 3.9 degrees  preoperatively versus 39.5
      degrees  +/- 2.8 degrees  postoperatively (P = 0.000) . The average correction of
      obturator height was (1.65 +/- 0.26) cm preoperatively versus (1.10 +/- 0.14) cm
      postoperatively (P = 0.000) . At 3 months, 6 months and 1 year post-operation,
      the average values of AI, SA, obturator angle and obturator height continued to
      fall. Both of them showed statistical improvement. Shifting index and descending
      angle of distal iliac end were 30.1% +/- 3.6% and 31.3 degrees  +/- 4.1 degrees 
      on average. Six (8.57%) Shenton lines were bad. CONCLUSIONS: The imaging
      evaluations of acetabulum and pelvis show marked improvements until 1 year in DDH
      patients after Salter innominate osteotomy. It provides data reference for
      operative evaluations through measuring the imaging parameters of truncation
      bone.

PMID- 24851893
TI  - [Plasma microRNA profile in immune thrombocytopenia: screening and verification].
AB  - OBJECTIVE: To screen the plasma microRNA (miRNA) profile of immune
      thrombocytopenia (ITP) patients. METHODS: Agilent 19.0 miRNA microarray was used
      to detect the expression profile of miRNA in plasma from 25 ITP patients and 20
      healthy controls from June 2012 to September 2013. The software programs of
      TargetScan and miRanda were used for predicting target genes associated with
      differential miRNA. Then gene ontology (GO) and pathway analysis were performed
      to explore the genes and pathways involved in the pathogenesis of ITP. And
      differential miRNA was validated by real-time quantitative polymerase chain
      reaction (PCR). RESULTS: A genome-wide miRNA array revealed 29 differential
      miRNAs in the plasma samples of ITP patients including 15 up-regulated and 14
      down-regulated miRNA. A total of 608 potential genes were predicted by TargetScan
      and miRanda.GO result showed that there were 475 (78.12%), 491(80.76%) and 533
      (87.66%) genes respectively involved in biological process, molecular function
      and cellular component.Enrichment test showed 9 GO terms had significant
      difference (P < 0.05). Pathway analysis showed that 157 pathways were associated
      with 608 genes.Enrichment test showed 25 pathways had significant difference (P <
      0.05). As revealed by real-time PCR, the expressions of miRNA4778-5p and
      miRNA4800-5p became obviously up-regulated while those of miRNA4707-5p,
      miRNA4721, miRNA3620-3p and miRNA378i decreased (all P < 0.05). The results
      agreed with those of microarray. CONCLUSIONS: The plasma differential miRNA
      profiles are identified in ITP patients. And miRNA is involved in calcium
      signaling pathway and T cell receptor signaling pathway may be associated with
      ITP pathogenesis.

PMID- 24851894
TI  - [Effect and mechanism of dantrolene on skeletal muscle of rats with severe scald
      injury].
AB  - OBJECTIVE: To explore the effect and mechanism of ryanodine receptor antagonist
      dantrolene on skeletal muscle of rats with severe scald injury. METHODS: A total
      of 56 Wistar rats were divided into control, scald and dantrolene treatment
      groups according to a random digital table. Rats in scald and dantrolene
      treatment groups were subject to 50% total body surface area (TBSA) full
      thickness scald by a 12-second immersion of back and a 6-second immersion of
      abdomen in 94  degrees C water and then received an intraperitoneal injection of
      Ringer's solution. At the same time, the rats in scald group received 5% mannitol
      through caudal vein while those in dantrolene treatment group received dantrolene
      2 mg/kg (dissolved in 5% mannitol). Rats in control group were sham-injured
      through an immersion of back and abdomen into 37  degrees C warm water. Tibialis
      anterior muscle samples were harvested at Days 1, 4 and 7 post-scalding. Changes
      of skeletal muscle ultrastructure were observed by transmission electron
      microscope, subcellular calcium ion (Ca(2+)) contents of skeletal muscle
      (including cytoplasm, mitochondria & sarcoplasm reticulum) were detected by
      electron probe X-ray microanalysis (EPMA) and the levels of calpain-1 and calpain
      2 protein were determined by Western blot. And the activities of calpain were
      detected by enzyme-linked immunosorbent assay. RESULTS: In scald group, assorted
      arrangement appeared immediately at Day 1 post-injury and partial disappearance
      of Z lines at Day 7 post-injury. There were no significant ultrastructure changes
      in dantrolene treatment group at Day 1 and 4 post-injury. Curled filament and
      mild fracture occurred merely in dantrolene treatment group at Day 7 post-injury.
      The cytoplasmic contents of Ca(2+) were significantly higher in scald group than
      those in control group at Day 1 and 4 ((0.964 +/- 0.060), (0.639 +/- 0.067) vs
      (0.266 +/- 0.029) umol/L respectively, all P < 0.05) while the contents of Ca(2+)
      within sarcoplasm reticulum were obviously lower in scald group than those in
      control group at Day 1 and 4 ((0.368 +/- 0.060), (0.814 +/- 0.089) vs (1.337 +/-
      0.112) umol/L respectively, all P < 0.05). However, those subcellular regions in
      dantrolene treatment group ((0.310 +/- 0.069), (0.490 +/- 0.039) and (1.241 +/-
      0.073), (1.161 +/- 0.094) umol/L) had no significant difference with control
      group (all P > 0.05). Calpain-1 and calpain-2 protein levels in scald group
      increased significantly at Day 1 and 4 post-injury versus control group (1.371 +/
      0.034, 1.214 +/- 0.030 vs 0.838 +/- 0.017 & 1.464 +/- 0.015, 1.390 +/- 0.023 vs
      0.806 +/- 0.026 respectively, all P < 0.05), whereas calpain-1 and calpain-2
      protein levels in dantrolene treatment (0.984 +/- 0.031, 0.935 +/- 0.023 and
      0.836 +/- 0.014, 0.741 +/- 0.020) obviously were lower than those in scald group
      respectively (all P < 0.05). The activities of calpain in scald and dantrolene
      treatment groups at Day 1, 4 and 7 post-injury were (8.33 +/- 0.21), (9.33 +/-
      0.21), (10.59 +/- 0.18) and (7.76 +/- 0.28), (7.86 +/- 0.20), (7.91 +/- 0.22)
      umol/L respectively while the activity of calpain in control group was (7.62 +/-
      0.19) umol/L. The activities of calpain in scald group were significantly higher
      than those in dantrolene treatment and control groups (all P < 0.05) whereas the
      activities of calpain in dantrolene treatment group had no obvious change versus
      control group (all P > 0.05). CONCLUSIONS: Dantrolene offers significant
      protection from skeletal muscle tissue damage and minimizes the ultrastructural
      change of tibialis anterior muscle induced by severe scald injury. The mechanism
      is probably through inhibiting an excessive release of Ca(2+) within sarcoplasm
      reticulum and down-regulated cytoplasmic expression and activity of calpain-1 and
      calpain-2.

PMID- 24851895
TI  - [Effects of adiponectin on endoplasmic reticulum stress-mediated apoptosis and
      cell cytoskeleton and its mechanism of podocytes cultured in high glucose].
AB  - OBJECTIVE: To explore the effects of adiponectin (APN) on high glucose-induced
      endoplasmic reticulum stress (ERS)-mediated apoptosis and cytoskeleton. METHODS:
      The conditionally immortal human glomerular podocytes were divided into normal
      glucose, mannitol, high glucose and high glucose with adiponectin groups. Flow
      cytometry was employed to assess cell apoptosis.Real-time polymerase chain
      reaction (PCR) and Western blot were used to detect the expressions of such ERS
      molecules as GRP78, CHOP and caspase 12 and desmin and TRPC6. Immunofluorescent
      staining was used to detect the changes in the skeleton of podocyte. RESULTS: (1)
      The apoptosis rate in high glucose group is significantly higher than the other
      groups (26.15% +/- 1.38% vs 2.39% +/- 0.58%, 4.84% +/- 0.87%, 16.71% +/- 1.15%,
      all P < 0.05). Compared with control group, the mRNA and protein expressions of
      GRP78, CHOP and caspase 12 were all up-regulated significantly in high glucose
      group (P < 0.05). The high glucose with adiponectin group could reduce the
      podocyte apoptosis by 10% and down-regulated the mRNA and protein expressions of
      GRP78, CHOP and caspase 12 versus high glucose group (all P < 0.05). (2) High
      glucose-induced podocyte caused the up-regulated expressions of TRPC6 and desmin
      (all P < 0.05) and it was inhibited by adiponectin (all P < 0.05). Additionally,
      immunofluorescent assay of high glucose-induced podocyte cytoskeleton showed
      disorderly F-actin and absent tensile fiber. Adiponectin prevented the F-actin
      cytoskeleton disruption under high glucose. CONCLUSION: Adiponectin plays a
      protective role in high glucose-induced podocyte through reducing endoplasmic
      reticulum stress-induced apoptosis and blunting the injury of cytoskeleton.

PMID- 24851896
TI  - [Comparison of biological characteristics and quantity of epidermal stem cells
      from hypertrophic scar skin and normal skin of human beings].
AB  - OBJECTIVE: To compare the biological characteristics of epidermal stem cells
      (ESCs) from hypertrophic scar and normal skin. METHODS: Epidermal stem cells were
      separated, enriched and adhered from 20 hypertrophic scars (scar group) and 20
      normal skins (control group). The morphology and growth characteristics of
      primary epidermal stem cells were observed. The absorbance (A) values of
      expression of Keratin 19, nucleoprotein p63 and integrin beta1 were tested by
      Western blot. And the genes of Oct-4 and Nanog were tested by quantitative
      reverse transcription-polymerase chain reaction (qRT-PCR). Flow cytometry was
      used to examine the markers of integrin CD29, integrin CD49f and Keratin 19 of
      ESCs. RESULTS: The primary cultured cells showed the similar shape and growth
      curve. By comparing the epidermal stem cells from scar groups and control groups,
      the absorbance values of the expression of Keratin 19, nucleoprotein p63 and
      integrin beta1 were 860 +/- 4, 712 +/- 3, 422 +/- 6 and 862 +/- 3, 707 +/- 9, 413
      +/- 6 (all P > 0.05). The expression values of Oct-4, Nanog were (7.79 +/-
      0.44)*10(-4), (5.96 +/- 0.36)*10(-4) and (7.93 +/- 0.29)*10(-4), (6.06 +/-
      0.35)*10(-4) (all P > 0.05). Percentages of positive cells expressing CD29, CD49f
      and Keratin 19 were (97.3 +/- 0.7)%, (94.6 +/- 1.1)%, (92.5 +/- 0.8)% and (98.8
      +/- 4.6)%, (98.9 +/- 0.4)%, (94.4 +/- 0.7)% respectively (all P < 0.05).
      CONCLUSIONS: The ESCs in hypertrophic scar have the same characteristics with
      ESCs in normal skin. However, the ESCs from hypertrophic scar are lower than that
      from normal skin.

PMID- 24851897
TI  - [Palmitate induced apoptosis in MC3T3-E1 cell by activation of nuclear factor
      kappa B].
AB  - OBJECTIVE: To explore whether palmitate-induced apoptosis of osteoblastic MC3T3
      E1 cell is mediated by an activation of nuclear factor-kappa B (NF-kappaB).
      METHODS: Cell viability was assessed with methyl thiazolyl tetrazolium (MTT)
      assay and cell apoptosis by Hochest 33258 staining. Palmitate was added at
      different timepoints and dosages.Western blot was used to evaluate the expression
      levels of IkappaBalpha, p-NF-kappaB p65 and NF-kappaB p65 protein. RESULTS:
      Palmitate led to a dose- and time-dependent decreases in cell viability and
      increase in cell apoptosis. Cell viability dropped to 54% and cleaved caspase-3
      increased 3.1-fold in cells treated with 500 umol/L palmitate compared to
      control. The level of p-NF-kappaB p65 protein markedly increased at 60 min post
      stimulation and reached a 2.96-fold increase of baseline level at 120 min (P <
      0.05) . The IkappaBalpha level markedly declined at 60 min post-stimulation and
      decreased by 57% at 120 min (P < 0.05) . Compared to the group with palmitate
      treatment alone, pyrrolidine dithiocarbamic acid (10/20 umol/L) significantly
      inhibited the palmitate-induced increase of p-NF-kappaB p65 (1.39 +/- 0.12, 1.25
      +/- 0.10 vs 1.76 +/- 0.14, both P < 0.05) , restored the palmitate-induced
      decrease of caspase-3 (2.24 +/- 0.28 vs 1.29 +/- 0.27, P < 0.05) and inhibited
      the palmitate-induced increase of cleaved caspase-3 (0.63 +/- 0.01 vs 1.13 +/-
      0.10, P < 0.05) . CONCLUSION: Palmitate induces apoptosis of MC3T3-E1 cell by an
      activation of NF-kappaB.

PMID- 24851898
TI  - [Effect of urinary Tamm-horsfall protein concentration changes under
      centrifugation and its association with urolithiasis formation in rats].
AB  - OBJECTIVE: To explore the concentration changes of Tamm-Horsefall protein (THP)
      under centrifugation in rat urine and discuss its association with urolithiasis
      formation. METHODS: A total of 40 Wistar rats were divided randomly into 4 groups
      of flying with stone (A), flying without stone (B), stone without flying (C) and
      control (D). After centrifugation, the THP concentrations of each group were
      measured by enzyme-linked immunosorbent assay (ELISA). Then urinary system was
      dissected, stained with hematoxylin & eosin and observed under electron
      microscopy to examine the distribution and number of each section. The SPSS 13.0
      software was used for data analyses. RESULTS: Group A showed significant
      difference in THP concentrations with groups C and D ( (11 +/- 4) vs (15 +/- 6),
      (17 +/- 4) ng/ml, P = 0.037 and 0.005).No statistically significant difference
      existed between groups A and B ((11 +/- 5) ng/ml, P = 0.998) or groups C and D (P
      = 0.422). Group B had significant difference in THP concentrations with groups D
      (P = 0.036). Regarding the number of stones in ureter, Group A had statistically
      significant difference with B (P = 0.029).However, there was no difference in the
      number of bladder stones.In kidney stones, there was significant difference (P =
      0.029) on "+ +" rating. CONCLUSION: Centrifugation may reduce the urinary
      concentration of THP so as cause urolithiasis formation in rats.

PMID- 24851899
TI  - Fast deterministic ptychographic imaging using X-rays.
AB  - We present a deterministic approach to the ptychographic retrieval of the wave at
      the exit surface of a specimen of condensed matter illuminated by X-rays. The
      method is based on the solution of an overdetermined set of linear equations, and
      is robust to measurement noise. The set of linear equations is efficiently solved
      using the conjugate gradient least-squares method implemented using fast Fourier
      transforms. The method is demonstrated using a data set obtained from a gold
      chromium nanostructured test object. It is shown that the transmission function
      retrieved by this linear method is quantitatively comparable with established
      methods of ptychography, with a large decrease in computational time, and is thus
      a good candidate for real-time reconstruction. 

PMID- 24851900
TI  - Correlating the effects of bone morphogenic protein to secreted soluble factors
      from fibroblasts and mesenchymal stem cells in regulating regenerative processes
      in vitro.
AB  - The capacity to regenerate complex tissue structures after amputation in humans
      is limited to the digit tip. In a comparable mouse digit model, which includes
      both distal regeneration-competent and proximal regeneration-incompetent regions,
      successful regeneration involves precise orchestration of complex
      microenvironmental cues, including paracrine signaling via heterogeneous cell
      cell interactions. Initial cellular processes, such as proliferation and
      migration, are critical in the formation of an initial stable cell mass and the
      ultimate regenerative outcome. Hence, the objective of these in vitro studies was
      to investigate the effect of soluble factors secreted by fibroblasts and
      mesenchymal stem cells (MSCs) on the proliferation and migration of cells from
      the regeneration-competent (P3) and -incompetent (P2) regions of the mouse digit
      tip. We found that P2 and P3 cells were more responsive to fibroblasts than MSCs
      and that the effects were mediated by bi-directional communication. To initiate
      understanding of the specific soluble factors that may be involved in the
      fibroblast-mediated changes in migration of P2 and P3 cells, bone morphogenic
      protein 2 (BMP2) was exogenously added to the medium. We found that changes in
      migration of P3 cells were similar when exposed to BMP2 or co-cultured with
      fibroblasts, indicating that BMP signaling may be responsible for the migratory
      response of P3 cells to the presence of fibroblasts. Furthermore, BMP2 expression
      in fibroblasts was shown to be responsive to tensile strain, as is present during
      wound closure. Therefore, these in vitro studies indicate that regenerative
      processes may be regulated by fibroblast-secreted soluble factors, which, in
      turn, are modulated by both cross-talk between heterogeneous phenotypes and the
      physical microenvironment of the healing site. 

PMID- 24851901
TI  - One Health: past successes and future challenges in three African contexts.
AB  - BACKGROUND: The recent emergence of zoonotic diseases such as Highly Pathogenic
      Avian Influenza (HPAI) and Severe Acute Respiratory Syndrome (SARS) have
      contributed to dominant Global Health narratives around health securitisation and
      pandemic preparedness, calling for greater co-operation between the health,
      veterinary and environmental sectors in the ever-evolving One Health movement. A
      decade later, One Health advocates face increasing pressure to translate the
      approach from theory into action. METHODOLOGY/PRINCIPAL FINDINGS: A qualitative
      case study methodology was used to examine the emerging relationships between
      international One Health dialogue and its practical implementation in the African
      health policy context. A series of Key Informant Interviews (n = 32) with policy
      makers, government officials and academics in Nigeria, Tanzania and Uganda are
      presented as three separate case studies. Each case examines a significant aspect
      of One Health operationalisation, framed around the control of both emerging and
      Neglected Zoonotic Diseases including HPAI, Human African Trypanosomiasis and
      rabies. The research found that while there is general enthusiasm and a strong
      affirmative argument for adoption of One Health approaches in Africa, identifying
      alternative contexts away from a narrow focus on pandemics will help broaden its
      appeal, particularly for national or regionally significant endemic and neglected
      diseases not usually addressed under a "global" remit. CONCLUSIONS/SIGNIFICANCE:
      There is no 'one size fits all' approach to achieving the intersectoral
      collaboration, significant resource mobilisation and political co-operation
      required to realise a One Health approach. Individual country requirements cannot
      be underestimated, dismissed or prescribed in a top down manner. This article
      contributes to the growing discussion regarding not whether One Health should be
      operationalised, but how this may be achieved.

PMID- 24851903
TI  - Switching the reaction course of electrochemical CO2 reduction with ionic
      liquids.
AB  - The ionic liquid 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide
      ([emim][Tf2N]) offers new ways to modulate the electrochemical reduction of
      carbon dioxide. [emim][Tf2N], when present as the supporting electrolyte in
      acetonitrile, decreases the reduction overpotential at a Pb electrode by 0.18 V
      as compared to tetraethylammonium perchlorate as the supporting electrolyte. More
      interestingly, the ionic liquid shifts the reaction course during the
      electrochemical reduction of carbon dioxide by promoting the formation of carbon
      monoxide instead of oxalate anion. With increasing concentration of [emim][Tf2N],
      a carboxylate species with reduced CO2 covalently bonded to the imidazolium ring
      is formed along with carbon monoxide. The results highlight the catalytic effects
      of the medium in modulating the CO2 reduction products. 

PMID- 24851904
TI  - Echinococcus P29 antigen: molecular characterization and implication on post
      surgery follow-up of CE patients infected with different species of the
      Echinococcus granulosus complex.
AB  - The protein P29 is a potential serological marker for post-treatment monitoring
      of cystic echinococcosis (CE) especially in young patients. We now have
      demonstrated that P29 is encoded in the Echinococcus genus by a single gene
      consisting of 7 exons spanning 1.2 kb of DNA. Variability of the p29 gene at
      inter- and intra-species level was assessed with 50 cDNA and 280 genomic DNA
      clones isolated from different E. granulosus s.l. isolates (E. granulosus sensu
      stricto (G1), E. equinus (G4), E. ortleppi (G5), E. canadensis (G6), E.
      canadensis (G7) and E. canadensis (G10)) as well as four E. multilocularis
      isolates. Scarce interspecies polymorphism at the p29 locus was observed and
      affected predominantly E. granulosus s.s. (G1), where we identified two alleles
      (A1 and A2) coding for identical P29 proteins and yielding in three genotypes
      (A1/A1, A2/A2 and A1/A2). Genotypic frequencies expected under Hardy-Weinberg
      equilibrium revealed a high rate of heterozygosity (47%) that strongly supports
      the hypothesis that E. granulosus s.s. (G1) is predominantly outbreeding.
      Comparative sequence analyses of the complete p29 gene showed that phylogenetic
      relationships within the genus Echinococcus were in agreement with those of
      previous nuclear gene studies. At the protein level, the deduced P29 amino acid
      (AA) sequences exhibited a high level of conservation, ranging from 97.9% AA
      sequence identity among the whole E. granulosus s.l. group to 99.58% identity
      among E. multilocularis isolates. We showed that P29 proteins of these two
      species differ by three AA substitutions without implication for antigenicity. In
      Western-blot analyses, serum antibodies from a human CE patient infected with E.
      canadensis (G6) strongly reacted with recombinant P29 from E. granulosus s.s.
      (G1) (recEg(G1)P29). In the same line, human anti-Eg(G1)P29 antibodies bound to
      recEcnd(G6)P29. Thus, minor AA sequence variations appear not to impair the
      prognostic serological use of P29. 

PMID- 24851905
TI  - Novel epigenetic target therapy for prostate cancer: a preclinical study.
AB  - Epigenetic events are critical contributors to the pathogenesis of cancer, and
      targeting epigenetic mechanisms represents a novel strategy in anticancer
      therapy. Classic demethylating agents, such as 5-Aza-2'-deoxycytidine
      (Decitabine), hold the potential for reprograming somatic cancer cells
      demonstrating high therapeutic efficacy in haematological malignancies. On the
      other hand, epigenetic treatment of solid tumours often gives rise to undesired
      cytotoxic side effects. Appropriate delivery systems able to enrich Decitabine at
      the site of action and improve its bioavailability would reduce the incidence of
      toxicity on healthy tissues. In this work we provide preclinical evidences of a
      safe, versatile and efficient targeted epigenetic therapy to treat hormone
      sensitive (LNCap) and hormone refractory (DU145) prostate cancers. A novel
      Decitabine formulation, based on the use of engineered erythrocyte (Erythro
      Magneto-Hemagglutinin Virosomes, EMHVs) drug delivery system (DDS) carrying this
      drug, has been refined. Inside the EMHVs, the drug was shielded from the
      environment and phosphorylated in its active form. The novel magnetic EMHV DDS,
      endowed with fusogenic protein, improved the stability of the carried drug and
      exhibited a high efficiency in confining its delivery at the site of action in
      vivo by applying an external static magnetic field. Here we show that Decitabine
      loaded into EMHVs induces a significant tumour mass reduction in prostate cancer
      xenograft models at a concentration, which is seven hundred times lower than the
      therapeutic dose, suggesting an improved pharmacokinetics/pharmacodynamics of
      drug. These results are relevant for and discussed in light of developing
      personalised autologous therapies and innovative clinical approach for the
      treatment of solid tumours. 

PMID- 24851909
TI  - 'Paper-light' is the right way to go.

PMID- 24851908
TI  - Design principles for efficient, repeated jumpgliding.
AB  - Combined jumping and gliding locomotion, or 'jumpgliding', can be an efficient
      way for small robots or animals to travel over cluttered terrain. This paper
      presents functional requirements and models for a simple jumpglider which
      formalize the benefits and limitations of using aerodynamic surfaces to augment
      jumping ability. Analysis of the model gives insight into design choices and
      control strategies for higher performance and to accommodate special conditions
      such as a slippery launching surface. The model informs the design of a robotic
      platform that can perform repeated jumps using a carbon fiber spring and a
      pivoting wing. Experiments with two different versions of the platform agree with
      predictions from the model and demonstrate a significantly greater range, and
      lower cost-of-transport, than a comparable ballistic jumper. 

PMID- 24851906
TI  - Different modes of retrovirus restriction by human APOBEC3A and APOBEC3G in vivo.
AB  - The apolipoprotein B editing complex 3 (A3) cytidine deaminases are among the
      most highly evolutionarily selected retroviral restriction factors, both in terms
      of gene copy number and sequence diversity. Primate genomes encode seven A3
      genes, and while A3F and 3G are widely recognized as important in the restriction
      of HIV, the role of the other genes, particularly A3A, is not as clear. Indeed,
      since human cells can express multiple A3 genes, and because of the lack of an
      experimentally tractable model, it is difficult to dissect the individual
      contribution of each gene to virus restriction in vivo. To overcome this problem,
      we generated human A3A and A3G transgenic mice on a mouse A3 knockout background.
      Using these mice, we demonstrate that both A3A and A3G restrict infection by
      murine retroviruses but by different mechanisms: A3G was packaged into virions
      and caused extensive deamination of the retrovirus genomes while A3A was not
      packaged and instead restricted infection when expressed in target cells.
      Additionally, we show that a murine leukemia virus engineered to express HIV Vif
      overcame the A3G-mediated restriction, thereby creating a novel model for
      studying the interaction between these proteins. We have thus developed an in
      vivo system for understanding how human A3 proteins use different modes of
      restriction, as well as a means for testing therapies that disrupt HIV Vif-A3G
      interactions. 

PMID- 24851910
TI  - International Nurses Day.

PMID- 24851911
TI  - Pre-diabetes and capturing opportunities to raise awareness.
AB  - This article explores the high risk of diabetes and cardiovascular diseases in
      adults over 18 years of age and recognises, through the literature, the potential
      role for nurses in engagement with diabetes prevention strategies in their
      everyday practice. It considers the latest international projections for
      diabetes, a critical review of evidence of how diabetes can be prevented and how
      effective methods of detection of pre-diabetes can be employed with every
      clinical encounter with adults who perhaps previously were not considered to be
      'at risk' of developing type 2 diabetes. Effective consultation approaches to
      raise diabetes awareness within populations and to enable tailored approaches to
      public health lifestyle advice are explored, to encourage each practitioner to
      'think diabetes' in every clinical encounter. 

PMID- 24851912
TI  - Dipping a toe into the specialist nursing pool.

PMID- 24851913
TI  - epic 3 Guidelines: saving lives.

PMID- 24851914
TI  - The art of noticing: essential to nursing practice.
AB  - Noticing is integral to the everyday practice of nurses; it is the pre-cursor for
      clinical reasoning, informing judgement and the basis of care. By noticing the
      nurse can pre-empt possible risks or support subtle changes towards recovery.
      Noticing can be the activity that stimulates action before words are exchanged,
      pre-empting need. In this article, the art of noticing is explored in relation to
      nursing practice and how the failure to notice can have serious consequences for
      those in care. 

PMID- 24851915
TI  - Are we preparing student nurses for final practice placement?
AB  - The aims of this research were to illuminate student nurses' perceptions of
      preparedness for final practice placement, and to ascertain factors that
      supported and hindered preparation for final placement practice. This
      phenomenological qualitative research was carried out in a UK higher education
      institution (HEI) with eight adult branch student nurses maintaining written
      diaries for the first 4 weeks of their final 10-week practice placement. Data
      were then analysed by means of an interpretive phenomenological approach (IPA).
      Results showed that students felt ill-prepared for placement. Eight clear themes
      emerged, including: being used as 'an extra pair of hands'; mentors appearing to
      treat student practice documentation as unimportant; and high staff expectations.
      Other themes were: mentor importance; students feeling that they lacked
      knowledge; and students feeling unsupported and stressed. In conclusion, although
      students felt that they lacked knowledge and were used as an extra pair of hands,
      they did show clinical competence. 

PMID- 24851916
TI  - To write or not to write: a nurse's account of writing for publication.
AB  - Writing for publication is often seen as an arduous, daunting task reserved
      mainly for those in academia. This paper represents the first author's experience
      over the past 2 years of working on writing papers for publication in the context
      of personal and academic development. The aim is to reflect on the first author's
      journey towards publication with the intention of encouraging nursing staff to
      make their work visible and validate their practice through publication. This
      personal journey was made easier by the encouragement, help and support of the
      second author, a university lecturer acting as a mentor, advisor and critical
      friend. This paper is also intended to assure and give courage to those who have
      considered writing about their practice but are reluctant to do so. 

PMID- 24851917
TI  - Choosing the 'right' people for nursing: can we recruit to care?
AB  - Can we recruit to care? A brief view of the recruitment of student nurses at a UK
      university is highlighted as an example of selecting the 'right' people for
      nursing careers. The Francis report advises that student nurses need to be both
      intelligent and caring, with an intrinsic desire to help others. They are
      required to be passionate about the values that underpin nursing and motivated to
      put the welfare of others above their own. When recruiting nurses from a society
      with values far removed from those desired by the nursing profession, finding the
      right people to become the workforce of the future is a difficult task. Academic
      and practice personnel interviewed potential student nurses with an emphasis on
      looking for caring attributes alongside the necessary educational requirements.
      The students were being recruited for a new humanised nursing curriculum with
      caring values at the heart of the educational experience. 

PMID- 24851918
TI  - Transforming primary care for the most vulnerable in society.

PMID- 24851919
TI  - The importance of measurement tools in building a safe environment.

PMID- 24851920
TI  - The Hillsborough disaster: how it has changed UK healthcare law. Part 1.
AB  - The 25th anniversary of the Hillsborough Stadium disaster was commemorated this
      year with memorial services and a toll of bells to remember the 96 who died that
      day. Their legacy is largely seen in safe, modern, all-seat stadia but it endures
      beyond football. Court cases resulting from the aftermath of the tragedy have
      helped shape healthcare law in the UK and in a short series of articles Richard
      Griffith highlights the impact the Hillsborough disaster has had, beginning with
      the development of the law in relation to psychiatric injury arising from
      another's negligent act. 

PMID- 24851921
TI  - Reflection: from staff nurse to nurse consultant. Part 8: learning from
      reflection.

PMID- 24851922
TI  - Spiro-fused six-membered N-heterocyclic carbene: a new scaffold toward unique
      properties and activities.
AB  - A six-membered N-heterocyclic carbene fused with a spiro-scaffold is designed.
      The new NHC shows stronger sigma-donation ability than typical 5-membered NHCs.
      This property leads to interesting reactivities of this spiro-fused six-membered
      NHC. For example, the NHC-BF3 Lewis pair complex can be readily prepared by using
      LiBF4 as the BF3 source, or through a direct bond-reconstruction of the
      tetrafluoroborate salt NHC.HBF4. 

PMID- 24851924
TI  - Strong effect of weak charging in suspensions of anisotropic colloids.
AB  - Suspensions of hard colloidal particles frequently serve as model systems in
      studies on fundamental aspects of phase transitions. But often colloidal
      particles that are considered as "hard" are in fact weakly charged. If the
      colloids are spherical, weak charging has only a weak effect on the structural
      properties of the suspension, which can be easily corrected for. However, this
      does not hold for anisotropic particles. We introduce a model for the interaction
      potential between charged ellipsoids of revolution (spheroids) based on the
      Derjaguin approximation of Debye-Huckel theory and present a computer simulation
      study on aspects of the system's structural properties and phase behaviour. In
      line with previous experimental observations, we find that even a weak surface
      charge has a strong impact on the correlation functions. A likewise strong impact
      is seen on the phase behaviour, in particular, we find stable cubatic order in
      suspensions of oblate ellipsoids. 

PMID- 24851923
TI  - Soluble endoglin, transforming growth factor-Beta 1 and soluble tumor necrosis
      factor alpha receptors in different clinical manifestations of preeclampsia.
AB  - BACKGROUND: Despite intensive research, the etiopathogenesis of preeclampsia (PE)
      remains uncertain. Inflammatory and angiogenic factors are thought to play
      considerable roles in this disease. The objective of this study was to
      investigate the association between soluble endoglin (sEng), transforming growth
      factor beta-1 (TGF-beta1) and tumor necrosis factor alpha soluble receptors (sTNF
      Rs) and the clinical manifestations of PE. METHODS: Plasma levels of sEng, TGF
      beta1 and sTNF-Rs were determined by ELISA in 23 non-pregnant, 21 normotensive
      pregnant and 43 PE women. PE women were stratified into subgroups according to
      the severity [mild (n = 12) and severe (n = 31)] and onset-time of the disease
      [early (n = 19) and late (n = 24)]. RESULTS: Pregnancy was associated with higher
      levels of sEng, sTNF-R1 and sTNF-R2 than the non-pregnant state. Moreover, PE
      women had higher levels of sEng and sTNF-R1 than normotensive pregnant women. No
      difference was found in TGF-beta1 levels, comparing the three study groups. Late
      PE had higher levels of sTNF-R1 and sTNF-R2 than early PE. No significant
      differences were found in sEng and TGF-beta1 comparing early and late PE. sEng
      levels were higher in severe PE than in mild PE and no difference was found for
      TGF-beta1, sTNF-R1 and sTNF-R2 levels. There was a positive correlation among
      sEng, TNF-R1 and sTNF-2 levels. Logistic regression analysis revealed that
      primiparity and sEng levels are independently associated with the development of
      PE. Furthermore, sEng levels are independently associated with the disease
      severity. CONCLUSIONS: These results suggest that pregnancy is a condition
      associated with higher levels of anti-angiogenic and pro-inflammatory factors
      than the non-pregnant state and that PE is associated with an imbalance of these
      factors in the maternal circulation.

PMID- 24851926
TI  - An in situ spectroscopic study of the local structure of oxyfluoride melts: NMR
      insights into the speciation in molten LiF-LaF3-Li2O systems.
AB  - The local structure of molten LaF3-LiF-Li2O has been investigated by high
      temperature NMR spectroscopy. The (139)La and (19)F chemical shifts have been
      measured as a function of temperature and composition. The NMR spectra show that
      Li2O reacts completely with LaF3 to form a LaOF compound in the solid state below
      the melting temperature of the sample. LaOF is not completely dissolved in the
      fluoride melt and solid LaOF is observed in the (19)F spectra for Li2O
      concentrations above 10 mol%. We discuss the local environment of lanthanum ions
      in molten LaF3-LiF-Li2O and compare the results to those with the LaF3-LiF-CaO
      system. The analysis of the temperature and Li2O concentration dependences of the
      (139)La and (19)F chemical shifts suggests that several kinds of lanthanum
      oxyfluoride long-lived LaOxFy(3-x-y) units are present in the melt. 

PMID- 24851925
TI  - Comparative analysis of maize (Zea mays) crop performance: natural variation,
      incremental improvements and economic impacts.
AB  - Grain yield from maize hybrids continues to improve through advances in breeding
      and biotechnology. Despite genetic improvements to hybrid maize, grain yield from
      distinct maize hybrids is expected to vary across growing locations due to
      numerous environmental factors. In this study, we examine across-location
      variation in grain yield among maize hybrids in three case studies. The three
      case studies examine hybrid improvement through breeding, introduction of an
      insect protection trait or introduction of a transcription factor trait
      associated with increased yield. In all cases, grain yield from each hybrid
      population had a Gaussian distribution. Across-location distributions of grain
      yield from each hybrid partially overlapped. The hybrid with a higher mean grain
      yield typically outperformed its comparator at most, but not all, of the growing
      locations (a 'win rate'). These results suggest that a broad set of environmental
      factors similarly impacts grain yields from both conventional- and biotechnology
      derived maize hybrids and that grain yields among two or more hybrids should be
      compared with consideration given to both mean yield performance and the
      frequency of locations at which each hybrid 'wins' against its comparators. From
      an economic standpoint, growers recognize the value of genetically improved maize
      hybrids that outperform comparators in the majority of locations. Grower adoption
      of improved maize hybrids drives increases in average U.S. maize grain yields and
      contributes significant value to the economy. 

PMID- 24851927
TI  - Progressive dysphagia in a patient with a history of cervical spine fusion.

PMID- 24851928
TI  - Prestroke physical activity is associated with good functional outcome and
      arterial recanalization after stroke due to a large vessel occlusion.
AB  - BACKGROUND: Although multiple studies and meta-analyses have consistently
      suggested that regular physical activity (PhA) is associated with a decreased
      stroke risk and recurrence, there is limited data on the possible preconditioning
      effect of prestroke PhA on stroke severity and prognosis. We aimed to study the
      association of prestroke PhA with different outcome variables in patients with
      acute ischemic stroke due to an anterior large vessel occlusion. METHODS: The
      Prestroke Physical Activity and Functional Recovery in Patients with Ischemic
      Stroke and Arterial Occlusion trial is an observational and longitudinal study
      that included consecutive patients with acute ischemic stroke admitted to a
      single tertiary stroke center. Main inclusion criteria were: anterior circulation
      ischemic stroke within 12 h from symptom onset; presence of a confirmed anterior
      large vessel occlusion, and functional independence previous to stroke. Prestroke
      PhA was evaluated with the International Physical Activity Questionnaire and
      categorized into mild, moderate and high levels by means of metabolic equivalent
      (MET) minutes per week thresholds. The primary outcome measure was good
      functional outcome at 3 months (modified Rankin scale <=2). Secondary outcomes
      were severity of stroke at admission, complete early recanalization, early
      dramatic neurological improvement and final infarct volume. RESULTS: During the
      study period, 159 patients fulfilled the above criteria. The mean age was 68
      years, 62% were men and the baseline NIHSS score was 17. Patients with high
      levels of prestroke PhA were younger, had more frequently distal occlusions and
      had lower levels of blood glucose and fibrinogen at admission. After multivariate
      analysis, a high level of prestroke PhA was associated with a good functional
      outcome at 3 months. Regarding secondary outcome variables and after adjustment
      for relevant factors, a high level of prestroke PhA was independently associated
      with milder stroke severity at admission, early dramatic improvement, early
      arterial recanalization after intravenous thrombolysis and lower final infarct
      volume. The beneficial association of prestroke PhA with stroke outcomes was
      already present with a cutoff point of 1,000 MET min/week, a level of PhA easily
      achieved by walking 1 h/day during 5 days or by doing a vigorous aerobic activity
      1 h/day twice a week. CONCLUSIONS: Prestroke PhA is independently associated with
      favorable stroke outcomes after a large vessel occlusion. Future research on the
      underlying mechanisms is needed to understand this neuroprotective effect of PhA.

PMID- 24851929
TI  - All-trans retinoic acid induces DU145 cell cycle arrest through Cdk5 activation.
AB  - BACKGROUND/AIMS: All-trans retinoic acid (ATRA), the active form of vitamin A,
      plays an important role in the growth arrest of numerous types of cancer cells.
      It has been indicated that cyclin-dependent kinase 5 (Cdk5) activity can be
      affected by ATRA treatment. Our previous results demonstrate the involvement of
      Cdk5 in the fate of prostate cancer cells. The purpose of this study is to
      examine whether Cdk5 is involved in ATRA-induced growth arrest of the castration
      resistant cancer cell line DU145 through up-regulating Cdk inhibitor protein,
      p27. METHODS: DU145 cells were treated with ATRA, and cell proliferation, protein
      expression, and protein localization of Cdk5/p27 were examined. Cell
      proliferation and cell cycle distribution were also determined under Cdk5
      inhibition induced by inhibitor or knockdown. RESULTS: ATRA treatment inhibited
      DU145 cell proliferation and significantly increased p27 expression through Cdk5
      up-regulation. Immunocytochemical data showed that a Cdk5 inhibitor reduced ATRA
      triggered nuclear distribution of p27 in DU145 cells. The proliferation
      inhibition and G1 phase accumulation of DU145 cells were significantly increased
      by ATRA treatment, whereas Cdk5 inhibitor and siRNA could reverse these effects.
      CONCLUSIONS: Our results demonstrate that ATRA induced growth inhibition in
      castration-resistant prostate cancer cells through activating Cdk5 and p27. We
      hope this finding will increase the knowledge of prostate cancer treatment and
      can be applied in patients' nutritional control in the future.

PMID- 24851934
TI  - Macitentan (Opsumit) for the treatment of pulmonary arterial hypertension.
AB  - The endothelin pathway is a key pathway for the pathogenesis of pulmonary
      arterial hypertension (PAH). Antagonism of this pathway is recommended as initial
      therapy in low-risk patient with PAH to inhibit fibrosis, cell proliferation, and
      inflammation caused by endothelin. Prior to October 2013, ambrisentan, a
      selective ETA receptor antagonist and bosentan, a dual ETA/ETB antagonist, were
      the only currently available agents for PAH targeting the endothelin pathway.
      Based on the results of the SERAPHIN trial, macitentan (brand name Opsumit(r)), a
      new ETA/ETB antagonist, has been US FDA approved to delay disease progression and
      reduce hospitalizations for PAH. SERAPHIN is the first ERA trial to use an event
      driven strategy with a composite primary end point of morbidity or mortality.
      Previous trials have focused on short-term outcomes, such as improved 6-min walk
      distance and WHO functional class.

PMID- 24851935
TI  - Estimation of the 6-digit level allele and haplotype frequencies of HLA-A, -B,
      and -C in Koreans using ambiguity-solving DNA typing.
AB  - Because Korean society is fast becoming multi-ethnic, the determination of
      ambiguous human leukocyte antigen (HLA) types using HLA allele frequencies is
      becoming less applicable. In this study, we focused on the development of new
      technical methods to directly resolve the ambiguities arising from HLA
      genotyping. One hundred and fifty unrelated healthy Korean adults were included
      in this study. All alleles from each HLA locus were first divided into 2-4
      groups, with each group amplified in a single PCR tube (multi-group-specific
      amplification, MGSA). To resolve phase ambiguities, some allele groups were also
      amplified separately in small group-specific amplification (SGSA) tubes. In order
      to then resolve incomplete sequence ambiguities, primers for MGSA and SGSA were
      initially designed to cover additional exons. If needed, a heterozygous ambiguity
      resolving primer (HARP) or sequence specific primer (SSP) was also used. When
      MGSA and SGSA methods were applied, the rate of phase ambiguity was greatly
      reduced to an average of 6% (1.3% in HLA-A, 15.7% in -B, and 2.0% in -C).
      Additional HARP and SSP methods could resolve all the phase ambiguities. Using
      our proposed method, we also detected three alleles that have not been previously
      reported in Korea, C*04:82, C*07:18, and C*08:22, and report 6-digit level HLA
      allele and haplotype frequencies among Koreans. In conclusion, the use of
      MGSA/SGSA for the initial amplification step is a cost-effective method
      facilitating timely and accurate reporting, given the continuing increase in the
      ethnic diversity of the Korean population. The MGSA described here can be
      applicable to various populations and thus could be shared by the majority of HLA
      typing laboratories. However, efforts to solve HLA ambiguity should continue,
      because SGSA, HARPs and SSPs would be specific to a particular population. 

PMID- 24851937
TI  - Diagnostic outcome of preoperative coagulation testing in children.
AB  - The value of routine coagulation testing instead of bleeding history alone in
      children, to predict bleeding risk prior to tonsillectomy and adenoidectomy has
      been questioned. Our objectives are to identify the causes of abnormal PT and/or
      aPTT in these patients, and to determine whether routine preoperative coagulation
      testing is effective in identifying children with a clinically significant
      coagulation abnormality prior to undergoing a procedure. In this study, data were
      extracted by chart review for 854 patients referred to the pediatric hematology
      service at Stony Brook University for the evaluation of an elevated PT and/or
      aPTT on preoperative testing. Seven hundred and ninety two of 854 reviewed charts
      (92.7%) contained sufficient data for analysis. On repeat testing, 393 (49.6%)
      had a laboratory abnormality identified. A potentially significant coagulation
      abnormality was identified in 32 of 792 patients (4%). For the remaining 760
      patients, the most common diagnosis was a lupus anticoagulant (n = 98, 24.6%) or
      a "presumed" lupus anticoagulant (n = 166, 41.6%). A positive personal or family
      bleeding history was documented in 268 patients (268/792 = 33.8%). Of these
      patients, only 107 (39.9%) had an abnormality identified on further work-up.
      Seventeen of the 32 patients with clinically significant bleeding disorders
      identified were found to have a positive bleeding history (17/32 = 53.1%).
      Routine preoperative coagulation testing identifies only a small number of
      children at increased risk for surgical bleeding. However, a "positive" bleeding
      history identifies only 60% of children found to have a clinically significant
      coagulation abnormality. Routine preoperative coagulation testing may serve as a
      useful adjunct to clinical history. 

PMID- 24851936
TI  - The effect of mechanical stimulation on mineralization in differentiating
      osteoblasts in collagen-I scaffolds.
AB  - Developing a viable and functional bone scaffold in vitro that is capable of
      surviving and bearing mechanical load in vivo requires an understanding of the
      cell biology of osteoprogenitor cells, particularly how they are influenced by
      mechanical stimulation during cell differentiation and maturation. In this study,
      mechanical load was applied using a modified FlexCell plate to impart confined
      compression to collagen-I scaffolds seeded with undifferentiated murine embryonic
      stem cells. The activity, presence, and expression of osteoblast-cadherin (OB
      Cad) and connexin-43, as well as various pluripotent and osteogenic markers were
      examined at 5-30 days of differentiation as cells were stimulated to
      differentiate to osteoblasts with and without applied mechanical load.
      Fluorescence recovery after photobleaching, immunofluorescence, viability, von
      Kossa, and real-time polymerase chain reaction assessments revealed that
      mechanical prestimulation of this cell-seeded scaffold altered the expression of
      OB-Cad and connexin-43 and resulted in significant differences in the structure
      and organization of mineralization present in the collagen matrix. Specifically,
      cells in gels that were loaded for 40 h after 5 days of differentiation and then
      left to fully differentiate for 30 days produced a highly structured honeycomb
      shaped mineralization in the matrix; an outcome that was previously shown to be
      indicative of late osteoblast/early osteocyte activity. This study highlights the
      potential of mechanical load to accelerate differentiation and enhance osteoblast
      communication and function during the differentiation process, and highlights a
      time point of cell differentiation within this scaffold to apply load in order to
      most effectively transduce a mechanical signal. 

PMID- 24851939
TI  - Enantioselective organocatalytic partial transfer hydrogenation of lactone-fused
      quinolines.
AB  - The first enantioselective synthesis of 4-aza-podophyllotoxin derivatives by
      partial transfer hydrogenation of lactone-fused quinolines was achieved using a
      chiral Bronsted acid catalyst. This reaction was extended to a large scope of
      substrates with good yields and enantioselectivities. 

PMID- 24851941
TI  - Expression profile and subcellular localization of GAPDH in the smooth muscle
      cells of human atherosclerotic plaque: an immunohistochemical and ultrastructural
      study with biological therapeutic perspectives.
AB  - Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) has long been considered a
      classical glycolytic enzyme involved exclusively in cytosolic energy production.
      Several recent studies, however, have demonstrated that GAPDH is a
      multifunctional protein whose presence and activity can be regulated by disease
      states and/or experimental manipulation. Expression levels of GAPDH have been
      shown to be altered in certain tumors as well as in proliferating and
      differentiating cells. Since dedifferentiation and proliferation of smooth muscle
      cells (SMCs) are important features of human atherosclerosis, we have
      characterized the expression profile of GAPDH in the SMCs of atherosclerotic
      plaques and its putative interrelationship with the synthetic/proliferative
      status of these cells utilizing the proliferating cell nuclear antigen (PCNA)
      antibody, a valuable marker of cell proliferation. Western blot data revealed
      that GAPDH was significantly upregulated in atherosclerotic plaque specimens.
      Immunohistochemical stains demonstrated that GAPDH accumulated in the nucleus of
      dedifferentiated SMCs that also showed positive immunoreactivity for PCNA, but
      remained cytoplasmatic in the contractile SMCs (PCNA-negative), thus reflecting
      the proliferative, structural and synthetic differences between them. We suggest
      that, in human atherosclerotic plaque, GAPDH might exert additional functions
      that are independent of its well-documented glycolytic activity and might play
      key roles in development of the disease. 

PMID- 24851940
TI  - Neuronal adaptation involves rapid expansion of the action potential initiation
      site.
AB  - Action potential (AP) generation is the key to information-processing in the
      brain. Although APs are normally initiated in the axonal initial segment,
      developmental adaptation or prolonged network activity may alter the initiation
      site geometry thus affecting cell excitability. Here we find that hippocampal
      dentate granule cells adapt their spiking threshold to the kinetics of the
      ongoing dendrosomatic excitatory input by expanding the AP-initiation area away
      from the soma while also decelerating local axonal spikes. Dual-patch soma-axon
      recordings combined with axonal Na(+) and Ca(2+) imaging and biophysical
      modelling show that the underlying mechanism involves distance-dependent
      inactivation of axonal Na(+) channels due to somatic depolarization propagating
      into the axon. Thus, the ensuing changes in the AP-initiation zone and local AP
      propagation could provide activity-dependent control of cell excitability and
      spiking on a relatively rapid timescale. 

PMID- 24851942
TI  - Birth and death of links control disease spreading in empirical contact networks.
AB  - We investigate what structural aspects of a collection of twelve empirical
      temporal networks of human contacts are important to disease spreading. We scan
      the entire parameter spaces of the two canonical models of infectious disease
      epidemiology--the Susceptible-Infectious-Susceptible (SIS) and Susceptible
      Infectious-Removed (SIR) models. The results from these simulations are compared
      to reference data where we eliminate structures in the interevent intervals, the
      time to the first contact in the data, or the time from the last contact to the
      end of the sampling. The picture we find is that the birth and death of links,
      and the total number of contacts over a link, are essential to predict outbreaks.
      On the other hand, the exact times of contacts between the beginning and end, or
      the interevent interval distribution, do not matter much. In other words, a
      simplified picture of these empirical data sets that suffices for epidemiological
      purposes is that links are born, is active with some intensity, and die.

PMID- 24851943
TI  - Impact of thoracic epidural analgesia on blood loss in radical retropubic
      prostatectomy.
AB  - INTRODUCTION: Radical retropubic prostatectomy (RRP) is associated with an
      increased risk of intraoperative blood loss and the necessity of transfusions.
      This prospective randomised clinical study evaluates the influence of thoracic
      epidural analgesia (TEA) on blood loss in RRP. MATERIALS AND METHODS: 235
      patients were randomised: TEA in group 1 (n = 116; general anaesthesia + TEA)
      comprised continuous administration of 0.25% bupivacaine, while group 2 (n = 119;
      general anaesthesia alone) received intravenous analgesia with fentanyl
      (intubation: 2 ug/kg; maintenance: 0.1-0.3 mg). A restrictive infusion regimen
      (<1,000 ml until specimen removal) was administered in both groups. Blood loss,
      infusion rates and anaesthesiological parameters were recorded and analysed using
      regression models and analyses of variance. RESULTS: Haemoglobin difference
      between the pre- and the first postoperative day (group 1: 3.35 +/- 1.16 g/dl;
      group 2: 3.56 +/- 1.42 g/dl; p = 0.19), overall blood loss (group 1: 665 +/-
      431.5 ml; group 2: 705 +/- 881 ml; p = 0.73) and transfusion rates (0.4%
      intraoperatively; 2.55% postoperatively; p = 1.0) did not show group differences.
      In regression analysis blood loss was influenced by preoperative haemoglobin
      levels (p < 0.0001), patients' weight (p = 0.018) and duration of the operation
      (p = 0.017). CONCLUSIONS: This study did not demonstrate a direct impact of TEA
      on intraoperative blood loss and transfusion rates in RRP. Further randomised
      clinical trials are needed to evaluate an impact of the different anaesthetic
      procedures presented alone or in combination on blood loss.

PMID- 24851945
TI  - Facing the challenges of structure-based target prediction by inverse virtual
      screening.
AB  - Computational target prediction for bioactive compounds is a promising field in
      assessing off-target effects. Structure-based methods not only predict off
      targets, but, simultaneously, binding modes, which are essential for
      understanding the mode of action and rationally designing selective compounds.
      Here, we highlight the current open challenges of computational target prediction
      methods based on protein structures and show why inverse screening rather than
      sequential pairwise protein-ligand docking methods are needed. A new inverse
      screening method based on triangle descriptors is introduced: iRAISE (inverse
      Rapid Index-based Screening Engine). A Scoring Cascade considering the reference
      ligand as well as the ligand and active site coverage is applied to overcome
      interprotein scoring noise of common protein-ligand scoring functions.
      Furthermore, a statistical evaluation of a score cutoff for each individual
      protein pocket is used. The ranking and binding mode prediction capabilities are
      evaluated on different datasets and compared to inverse docking and pharmacophore
      based methods. On the Astex Diverse Set, iRAISE ranks more than 35% of the
      targets to the first position and predicts more than 80% of the binding modes
      with a root-mean-square deviation (RMSD) accuracy of <2.0 A. With a median
      computing time of 5 s per protein, large amounts of protein structures can be
      screened rapidly. On a test set with 7915 protein structures and 117 query
      ligands, iRAISE predicts the first true positive in a ranked list among the top
      eight ranks (median), i.e., among 0.28% of the targets. 

PMID- 24851946
TI  - A surrogate marker of airway hyperresponsiveness in patients with bronchial
      asthma.

PMID- 24851944
TI  - Intra-subtype variation in enteroadhesion accounts for differences in epithelial
      barrier disruption and is associated with metronidazole resistance in
      Blastocystis subtype-7.
AB  - Blastocystis is an extracellular, enteric pathogen that induces intestinal
      disorders in a range of hosts including humans. Recent studies have identified
      potential parasite virulence factors in and host responses to this parasite;
      however, little is known about Blastocystis-host attachment, which is crucial for
      colonization and virulence of luminal stages. By utilizing 7 different strains of
      the parasite belonging to two clinically relevant subtypes ST-4 and ST-7, we
      investigated Blastocystis-enterocyte adhesion and its association with parasite
      induced epithelial barrier disruption. We also suggest that drug resistance in ST
      7 strains might result in fitness cost that manifested as impairment of parasite
      adhesion and, consequently, virulence. ST-7 parasites were generally highly
      adhesive to Caco-2 cells and preferred binding to intercellular junctions. These
      strains also induced disruption of ZO-1 and occludin tight junction proteins as
      well as increased dextran-FITC flux across epithelial monolayers. Interestingly,
      their adhesion was correlated with metronidazole (Mz) susceptibility. Mz
      resistant (Mzr) strains were found to be less pathogenic, owing to compromised
      adhesion. Moreover, tolerance of nitrosative stress was also reduced in the Mzr
      strains. In conclusion, the findings indicate that Blastocystis attaches to
      intestinal epithelium and leads to epithelial barrier dysfunction and that drug
      resistance might entail a fitness cost in parasite virulence by limiting entero
      adhesiveness. This is the first study of the cellular basis for strain-to-strain
      variation in parasite pathogenicity. Intra- and inter-subtype variability in
      cytopathogenicity provides a possible explanation for the diverse clinical
      outcomes of Blastocystis infections. 

PMID- 24851947
TI  - The relationship between total serum IgE levels and atopic sensitization in
      subjects with or without atopic dermatitis.

PMID- 24851948
TI  - IL-33 promotes the induction and maintenance of Th2 immune responses by enhancing
      the function of OX40 ligand.
AB  - BACKGROUND: In Th2 immune responses, TSLP is a key player by induction of OX40
      ligand (OX40L) on dendritic cells (DCs), which is the trigger to induce Th2 cell
      mediated allergic cascade. Thus, TSLP-DC-OX40L axis might be the principal
      pathway in the inflammatory cascades in atopic dermatitis and asthma. IL-33,
      which is produced by epithelial cells, has been implicated in the Th2 immune
      responses and pathogenesis of the allergic disorders. However, the role of IL-33
      in the Th2-polarizing TSLP-DC-OX40L axis still remains largely elusive. We
      focused on the ability of IL-33 to promote OX40L-mediated Th2 responses. METHODS:
      Purified human naive or memory CD4+ T cells were stimulated with recombinant
      OX40L or TSLP-treated DCs (TSLP-DCs) in the presence of IL-33, and the cytokine
      production by the primed T cells was examined. We also performed
      immunohistochemical analyses for the expression of IL-33 in specimens of lymph
      node and skin from the patients with atopic dermatitis. RESULTS: IL-33 remarkably
      enhanced TSLP-DCs-driven or OX40L-driven Th2 responses from naive T cells and the
      Th2 functional attributes of CRTH2+ CD4+ Th2 memory cells by the increased
      production of IL-5, IL-9, and IL-13. In addition, IL-33 was expressed in the
      nuclei of epithelial cells in not only skin lesion but also lymph nodes of the
      patient with atopic dermatitis, suggesting a specialized role in adaptive T cell
      priming phase. CONCLUSIONS: IL-33 works as a positive regulator of TSLP-DC-OX40L
      axis that initiates and maintains the Th2 cell-mediated inflammatory responses,
      and therefore, it would be a new therapeutic target for the treatment of allergic
      disorders.

PMID- 24851949
TI  - Rapamycin attenuates pulmonary allergic vasculitis in murine model by reducing
      TGF-beta production in the lung.
AB  - BACKGROUND: Rapamycin has been reported to inhibit mesenchymal cell proliferation
      in a murine model of pulmonary fibrosis. In the present study, we examined the
      effects of rapamycin on vascular remodeling including intraluminal myofibroblast
      proliferation in a murine model of allergic vasculitis with eosinophil
      infiltration. METHODS: C57BL/6 mice were sensitized with ovalbumin (OVA) and
      alum. The positive controls were exposed to aerosolized OVA daily for 7 days. The
      other group of mice was administered with rapamycin (1mg/kg) intraperitoneally,
      in parallel with daily exposure to aerosolized OVA for 7 days. On the 3rd and 7th
      day, bronchoalveolar lavage (BAL) was performed and the lungs were excised for
      pathological analysis. Cell differentials were determined and concentrations of
      IL-4, IL-5, IL-13 and TGF-beta in the BAL fluid (BALF) were measured. Semi
      quantitative analysis of pathological changes in the pulmonary arteries was
      evaluated according to the severity of vasculitis. RESULTS: The number of
      eosinophils in BALF was reduced significantly in the mice treated with rapamycin
      compared to the positive control. There was a significant decrease in the TGF
      beta concentration of the BALF in the rapamycin-treated group compared to that of
      the positive control. The pathological scores were reduced significantly in the
      rapamycin-treated group compared to the positive control group. Intraluminal
      myofibroblasts in pulmonary arteries were reduced dramatically in the rapamycin
      treated group compared to the positive control group. CONCLUSIONS: Rapamycin
      suppressed pulmonary vascular remodeling in a murine model of allergic vasculitis
      with eosinophil infiltration through reducing eosinophil infiltration and TGF
      beta production in the lung and inhibition against biological action of TGF-beta.

PMID- 24851950
TI  - Iron and copper as virulence modulators in human fungal pathogens.
AB  - Fungal pathogens have evolved sophisticated machinery to precisely balance the
      fine line between acquiring essential metals and defending against metal
      toxicity. Iron and copper are essential metals for many processes in both fungal
      pathogens and their mammalian hosts, but reduce viability when present in excess.
      However, during infection, the host uses these two metals differently. Fe has a
      long-standing history of influencing virulence in pathogenic fungi, mostly in
      regards to Fe acquisition. Numerous studies demonstrate the requirement of the Fe
      acquisition pathway of Candida, Cryptococcus and Aspergillus for successful
      systemic infection. Fe is not free in the host, but is associated with Fe-binding
      proteins, leading fungi to develop mechanisms to interact with and to acquire Fe
      from these Fe-bound proteins. Cu is also essential for cell growth and
      development. Essential Cu-binding proteins include Fe transporters, superoxide
      dismutase (SOD) and cytochrome c oxidase. Although Cu acquisition plays critical
      roles in fungal survival in the host, recent work has revealed that Cu
      detoxification is extremely important. Here, we review fungal responses to
      altered metal conditions presented by the host, contrast the roles of Fe and Cu
      during infection, and outline the critical roles of fungal metal homeostasis
      machinery at the host-pathogen axis.

PMID- 24851951
TI  - Multi-walled carbon nanotubes, natural organic matter, and the benthic diatom
      Nitzschia palea: "a sticky story".
AB  - Different effects of multi-walled carbon nanotubes (MWCNTs) on the freshwater
      diatom Nitzschia palea were examined. MWCNTs used in this study (MWCNT) were
      dispersed either by sonication without (MWCNT sonicated) or with a realistic
      concentration (10 mg L(-1)) of Natural Organic Matter (MWCNT+NOM). A pocket-size
      device was designed to distinguish shading effect (using MWCNT suspensions as
      external filters) from total exposure effect of MWCNT sonicated and MWCNT+NOM on
      benthic algae. This study demonstrates that cell division was strongly inhibited
      after a 48 h exposure to MWCNT+NOM compared to MWCNT sonicated. This device did
      not yield a quantifiable contribution of shading to growth inhibition of MWCNT
      sonicated and below 10 mg L(-1) of MWCNT+NOM. In all cases, neither lethal
      effects nor drops in photosynthetic quantum yield were observed. After a 6-d
      exposure, a complete growth recovery was observed for all conditions except at
      the highest concentration of MWCNT+NOM. Different microscopic approaches using
      carbohydrates markers revealed the strong affinity between MWCNT and
      extracellular polymeric substances (EPS) produced by N. palea. These seem to
      constitute a defensive mechanism against MWCNT.

PMID- 24851952
TI  - Warty intralymphatic histiocytosis successfully treated with topical tacrolimus.

PMID- 24851953
TI  - Heat, pressure and light-induced interconversion of bisdithiazolyl radicals and
      dimers.
AB  - The heterocyclic bisdithiazolyl radical 1b (R1 = Me, R2 = F) crystallizes in two
      phases. The alpha-phase, space group P21/n, contains two radicals in the
      asymmetric unit, both of which adopt slipped pi-stack structures. The beta-phase,
      space group P21/c, consists of cross-braced pi-stacked arrays of dimers in which
      the radicals are linked laterally by hypervalent 4-center 6-electron S...S-S...S
      sigma-bonds. Variable-temperature magnetic susceptibility measurements on alpha
      1b indicate Curie-Weiss behavior (with Theta = -14.9 K), while the dimer phase
      beta-1b is diamagnetic, showing no indication of thermal dissociation below 400
      K. High-pressure crystallographic measurements indicate that the cross-braced pi
      stacked arrays of dimers undergo a wine-rack compression, but the dimer remains
      intact up to 8 GPa (at ambient temperature). The resistance of beta-1b to
      dissociate under pressure, also observed in its conductivity versus pressure
      profile, is in marked contrast to the behavior of the related dimer beta-1a (R1 =
      Et, R2 = F), which readily dissociates into a pair of radicals at 0.8 GPa. The
      different response of the two dimers to pressure has been rationalized in terms
      of differences in their linear compressibilities occasioned by changes in the
      degree of cross-bracing of the pi-stacks. Dissociation of both dimers can be
      effected by irradiation with visible (lambda = 650 nm) light; the transformation
      has been monitored by optical spectroscopy, magnetic susceptibility measurements,
      and single crystal X-ray diffraction. The photoinduced radical pairs persist up
      to temperatures of 150 K (beta-1b) and 242 K (beta-1a) before reverting to the
      dimer state. Variable-temperature optical measurements on beta-1b and beta-1a
      have afforded Arrhenius activation energies of 8.3 and 19.6 kcal mol(-1),
      respectively, for the radical-to-dimer reconversion. DFT and CAS-SCF calculations
      have been used to probe the ground and excited electronic state structures of the
      dimer and radical pair. The results support the interpretation that the ground
      state interconversion of the dimer and radical forms of beta-1a and beta-1b is
      symmetry forbidden, while the photochemical transformation is symmetry allowed.

PMID- 24851954
TI  - Searching for answers and validation: Australian women's experiences of coping
      with the adverse sexual effects of antidepressants.
AB  - Sexual difficulties relating to selective serotonin reuptake inhibitor (SSRI)
      medication have an impact on quality of life and are a common cause for non
      adherence to medication. While most research has focussed on the prevalence and
      treatment of sexual difficulties, little is known about how patients cope with
      the adverse sexual effects of SSRIs. This qualitative study, using Interpretive
      Phenomenological Analysis (IPA), investigated the experiences of 10 Australian
      women currently coping with the adverse sexual effects ofthis antidepressant by
      conducting semi-structured interviews. This paper presents one major theme from
      the study and reports the findings related to women's self-reported experiences
      of interacting with GPs in their search for answers and validation of their
      concerns. Findings from the study add to the current literature by providing an
      insight into how interactions with GPs impact on women's abilities to cope with
      adverse sexual effects. Empathic discussions and shared decision-making between
      GPs and women can provide the opportunity to improve the management of the
      adverse sexual effects of SSRIs and may lead to improved outcomes for women.

PMID- 24851956
TI  - Smart systems and personalized health: the real challenge of bridging the
      innovation gap.
AB  - Smart miniaturized systems, emerging from the integration of heterogeneous
      technologies like micro- and nano electronics, photonics, biotechnology,
      materials and information & communication technologies are considered today,
      after two decades of intensive public support, proven concepts and functional
      prototypes, as key enablers opening up new opportunities for healthcare and in
      particular personalized health. They offer an enhanced ability to sense, detect,
      analyze, communicate, respond, and monitor phenomena from macro (e.g. body,
      tissues) to nano scale (e.g. molecules, genes). For the majority of these
      projects, planning for the next phase of prototype validation, product design,
      supply chain, user targeting, clinical validation and commercial roll-out are now
      taking full attention. The new EU Framework Program for Research and Innovation,
      Horizon 2020, is focusing on technology transfer support and building ecosystems
      and value chains to ensure better time to market and higher impact of knowledge
      based technologies. The state-of-the-art and upcoming challenges for the
      implementation of H2020 and new opportunities in smart systems for pHealth are
      discussed in the paper. 

PMID- 24851957
TI  - Policy Management Standards Enabling Trustworthy pHealth.
AB  - Current paradigm changes for improving safety, quality and efficiency of care
      processes under massive deployment of information and communication technologies
      (ICT) place high requirements on privacy and security. These mainly focus on
      privilege management and access control harmonized in international standards and
      their further evolution. NIST and ISO, but especially HL7 play a prominent role
      in this context. Starting with classic role-based access control (RBAC)
      foundations to new specifications for security and privacy labeling of segmented
      health information, HL7 security is presented as a scalable intermediate solution
      on the way to comprehensive privilege management and access control by explicit,
      ontology-based, formal and therefore machine-processable policies. The
      successfully balloted HL7 labeling specification supports context-sensitive
      communication and cooperation between different stakeholders and processes with
      different purposes of use, based on meta-data of information, actors and
      processes involved. Basics of policy management and practical solutions are
      discussed. 

PMID- 24851959
TI  - Interoperable ICT and Telemedicine.

PMID- 24851958
TI  - The internet of things for personalized health.
AB  - Advances in information and communications technologies (ICT) enable new
      personalized health care concepts which are often characterized by four "P"
      terms, i.e. personalized, predictive, preventive and participatory. However, real
      world implementations of the complete 4P spectrum hardly exist today. The
      Internet of Things (IoT) has been defined as an extension to the current Internet
      that enables pervasive communication between the physical and the virtual world.
      Smart devices and enabling elements like Near Field Communication (NFC) and Radio
      Frequency Identification (RFID) technology already exist and increasingly will be
      a mainstream element of our lives. This future vision paper attempts to assess if
      and how the Internet of Things for personalized health (IoT4pH) can help to
      facilitate the 4P healthcare paradigm and discusses related challenges and
      opportunities. 

PMID- 24851960
TI  - Conceptual Model Formalization in a Semantic Interoperability Service Framework:
      Transforming Relational Database Schemas to OWL.
AB  - Healthcare information is distributed through multiple heterogeneous and
      autonomous systems. Access to, and sharing of, distributed information sources
      are a challenging task. To contribute to meeting this challenge, this paper
      presents a formal, complete and semi-automatic transformation service from
      Relational Databases to Web Ontology Language. The proposed service makes use of
      an algorithm that allows to transform several data models of different domains by
      deploying mainly inheritance rules. The paper emphasizes the relevance of
      integrating the proposed approach into an ontology-based interoperability service
      to achieve semantic interoperability. 

PMID- 24851961
TI  - Representing the Glasgow Coma Scale in IT: Proper Specification is Required for
      Assessment Scales.
AB  - In healthcare a huge amount of assessment scales and score systems are in use to
      abbreviate and summarize the results of clinical observations to interpret a
      patient's condition in a valid and reliable manner. It is challenging to convey
      the information in a semantic interoperable form to other systems. A bad approach
      would be to invent individual models for each of them. Within this paper we would
      like to demonstrate that a generic model is sufficient by demonstrating the
      realization with the Glasgow Coma Scale. 

PMID- 24851962
TI  - A Personal Health Record System for Diabetes Care Conforming to the ISO 16527
      Interoperability Requirements.
AB  - A Personal Health Record (PHR) is a health information repository controlled and
      managed directly by a patient or his/her custodian, or a person interested in
      his/her own health. PHR System's adoption and compliance with international
      standards is foremost important because it can help to meet international,
      national, regional or institutional interoperability and portability policies. In
      this paper, an interoperable PHR System for supporting the control of type 2
      diabetes mellitus is proposed, which meets the mandatory interoperability
      requirements proposed in the Personal Health Record System Functional Model
      standard (ISO 16527). After performing a detailed analysis of different
      applications and platforms for the implementation of electronic Personal Health
      Records, the adaptation of the Indivo Health open source platform was completed.
      Interoperability functions were added to this platform by integrating the Mirth
      Connect platform. The assessment of the platform's interoperability capabilities
      was carried out by a group of experts, who verified the interoperability
      requirements proposed in the ISO 16527 standard. 

PMID- 24851963
TI  - Integration of telehealth and telecare: the implementation model for chronic
      disease management in the veneto region.
AB  - The integration of health and social care is the latest dogma for improving the
      quality of care for chronic and frail patients. In the Veneto Region, a unique
      platform has been developed for the provision of both telecare and telehealth to
      chronic patients that are equipped at home with a personal health system for real
      time detection of emergencies situations and to measure their clinical parameters
      according to a plan scheduled by their clinician. The integrated service is
      centrally managed by a regional eHealth center that represents the point of
      intermediation between the patient and the health and social care professionals. 

PMID- 24851965
TI  - Solutions for Personalized Care and mHealth Applications.

PMID- 24851964
TI  - Towards automated biomedical ontology harmonization.
AB  - The use of biomedical ontologies is increasing, especially in the context of
      health systems interoperability. Ontologies are key pieces to understand the
      semantics of information exchanged. However, given the diversity of biomedical
      ontologies, it is essential to develop tools that support harmonization processes
      amongst them. Several algorithms and tools are proposed by computer scientist for
      partially supporting ontology harmonization. However, these tools face several
      problems, especially in the biomedical domain where ontologies are large and
      complex. In the harmonization process, matching is a basic task. This paper
      explains the different ontology harmonization processes, analyzes existing
      matching tools, and proposes a prototype of an ontology harmonization service.
      The results demonstrate that there are many open issues in the field of
      biomedical ontology harmonization, such as: overcoming structural discrepancies
      between ontologies; the lack of semantic algorithms to automate the process; the
      low matching efficiency of existing algorithms; and the use of domain and top
      level ontologies in the matching process. 

PMID- 24851966
TI  - Systematic Review of Interventions Supported by ICT for the Prevention Treatment
      of Occupational Stress.
AB  - PROBLEM: Stress-related disorders have become one of the main problems of public
      health in many countries and of worldwide organizations, and they are expected to
      become more common in the forthcoming decades. OBJECTIVE: This article aims at
      providing a systematic review and a descriptive evaluation of the interventions
      supported by ICT for the prevention and treatment of occupational stress.
      METHODS: A systematic review of five databases (EBSCO, The Cochrane Library,
      PubMed, ScienceDirect and IEEEXplorer) was carried out. RESULTS: This article
      provides a quantitative and qualitative description of 21 studies about
      occupational stress interventions supported by ICT. The following factors were
      considered for the analysis: impact of the intervention, design of the study,
      type of intervention, purpose of the intervention, type of instrument for the
      measurement of occupational stress, and type of ICT used. CONCLUSIONS: The
      systematic review demonstrated that interventions supported by ICT for the
      prevention and treatment of occupational stress are scarce but effective.

PMID- 24851967
TI  - Augmented reality cube game for cognitive training: an interaction study.
AB  - There is the potential that cognitive activity may delay cognitive decline in
      people with mild cognitive impairment. Games provide both cognitive challenge and
      motivation for repeated use, a prerequisite for long lasting effect. Recent
      advances in technology introduce several new interaction methods, potentially
      leading to more efficient, personalized cognitive gaming experiences. In this
      paper, we present an Augmented Reality (AR) cognitive training game, utilizing
      cubes as input tools, and we test the cube interaction with a pilot study. The
      results of the study revealed the marker occlusion problem, and that novice AR
      users can adjust to the developed AR environment after a small number of
      sessions. 

PMID- 24851969
TI  - Wearable and implantable devices and systems.

PMID- 24851968
TI  - Mobile Display of Information about Aggregated Antibiotic Resistance in the
      Hospital Setting Supported by Near Field Communication.
AB  - Antibiotic resistance is a heterogeneous phenomenon. It does not only differ
      between countries or states, but also between wards of hospitals, where different
      resistance patterns have been found. To support clinicians in administering
      empiric antibiotic therapy, we developed software to present information about
      antibiotic resistance using a mobile concept. A pre-existing infrastructure was
      deployed as the server component. The systems analyze and aggregate data from
      laboratory information systems, generating statistical data on antibiotic
      resistance. The information is presented to the Android client using a
      Representational State Transfer (REST) interface. Geographical localization is
      performed using near field communication (NFC) tags. The prototype provides
      tabulated data concerning antibiotic resistance patterns in the wards of a
      hospital. Using Android, NFC, and data caching, the usability of the system is
      estimated to be high. We hypothesize that antibiotic stewardship in hospitals can
      be supported by this software, thus improving medical monitoring of antibiotic
      resistance. Future studies in a productive environment are needed to measure the
      impact of the system on the outcome of patient care. 

PMID- 24851970
TI  - Reflection/Transmission study of two fabrics with microwave properties.
AB  - In this study, the transmission and reflection of two conductive fabrics are
      investigated in the frequency range from 2 to 18 GHz. One of the fabrics is a non
      woven polypyrrole, and the other consists of a polyethylene warp with steel
      threads in the weft. Reflection and transmission measurements are performed in
      order to characterize the electromagnetic properties of the materials. Reflection
      measurements are performed for two polarizations at normal, 0 degrees , and 60
      degrees  incident angles. Transmission measurements are also done for two
      polarization directions at normal incidence. The results show that the fabric
      with the steel filler reflects most of the incident radiation, and has very low
      transmission with some polarization dependence. The polypyrrole non-woven fabric,
      on the other hand, has reflection and transmission properties that show that it
      is absorbing the incident radiation. Wearable on-body sensors that in addition
      are comfortable to wear can be integrated in the textile of clothes. These
      sensors can e.g., be used to monitor health or analyze gait. The fabrics have the
      potential to be used in health applications when designing on-body sensors, e.g.
      for movement analysis. 

PMID- 24851971
TI  - Human activity classification with inertial sensors.
AB  - Monitoring human physical activity has become an important research area and is
      essential to evaluate the degree of functional performance and general level of
      activity of a person. The discrimination of daily living activities can be
      implemented with machine learning techniques. A public dataset provided during
      the European Symposium on Artificial Neural Networks 2013, with time and
      frequency domain features extracted from raw signals of the smartphone inertial
      sensors, was used to implement and evaluate an activity classifier. Using a
      decision tree classifier, an accuracy of 86% was achieved for the classification
      of walk, climb stairs, stand, sit, and lay down. The results obtained suggest
      that the smartphone's inertial sensors could be used for an accurate physical
      activity classification even with real-time requirements. 

PMID- 24851972
TI  - Transcutaneous assessment of glomerular filtration rate.
AB  - Glomerular filtration rate (GFR) is considered the best parameter for the
      assessment of renal function, being usually determined on the basis of urine or
      plasma clearance of exogenous renal markers. The common methodology is invasive,
      time consuming and cumbersome, with multiple blood and/or urine sampling and
      following laboratory assays required. The method detailed here allows to
      transcutaneously determine the renal function in awake animals, in a non-invasive
      and efficient manner by using an electronic device which detects the fluorescence
      emitted through the skin from the renal marker FITC-Sinistrin. A crucial target
      has been to improve the fixation of the device, which is dependent on the skin
      structure. For validation, the technique has been compared with the classical
      clearance method, and its robustness has been demonstrated in healthy and
      diseased murine models. Moreover, the method allows sequential measurements in
      the same individual. Thus progression and recovery of renal failure can be
      followed. Therefore, its future application in humans would allow an accurate and
      appropriate prediction and monitoring of patients with established kidney disease
      over time. Furthermore, it will be possible to observe those patients under other
      pathological conditions with associated risk of developing renal problems. 

PMID- 24851973
TI  - Inter-BAN Interference Mitigation: A Correlated Equilibrium Perspective.
AB  - A Body Area Network (BAN) is a wireless network of wearable or implantable
      computing devices. A BAN typically consists of several miniaturized radio-enabled
      body sensor/actuator that communicate with a single coordinator. Medical
      applications usually impose stringent constraints on the BAN operational
      reliability, quality of service, and power consumption. However, as there is no
      coordination among multiple co-located BANs, cross-interference could make
      achieving these objectives a challenging problem. Assuming Time Division Multiple
      Access (TDMA) at each BAN, this paper investigates the ability of regret matching
      based transmission scheduling algorithm to ease the impact of inter-BAN
      interference. This scheduling algorithm uses pattern of past interference for
      implicit coordination between different BAN transmissions. Simulation results
      demonstrate potential benefits of the proposed scheme for inter-BAN interference
      mitigation. 

PMID- 24851974
TI  - A mobile system for the collection of clinical data and EEG signals by using the
      sana platform.
AB  - Nowadays, more than 450 millions of people around the world suffer from mental
      disorders. One of the main problems of that type of illnesses is the lack of
      early detection, generally due to the reduced number of professionals specialized
      in mental health, especially in low- and middle-income countries. This article
      aims at describing the process of construction of an m-Health system that
      supports the collection of clinical data, including EEG signals, in order to
      assist the initial assessment of neurologic problems. The system has been mainly
      developed by using low-cost technology, implemented under the open-source
      platform SANA, and integrating a non-professional EEG device for the acquisition
      of bioelectric signals of the brain. The functionalities of this application and
      its usefulness have been evaluated by a group of six experts who concluded that
      a) the system implements 100% of the functionalities described in the system
      design phase, and b) the usefulness of the system's functionalities is 96%. 

PMID- 24851976
TI  - Security, privacy, safety, trust and ethics.

PMID- 24851975
TI  - A vital signs telemonitoring system - interoperability supported by a personal
      health record systema and a cloud service.
AB  - This article presents the development process of an acquisition and data storage
      system managing clinical variables through a cloud storage service and a Personal
      Health Record (PHR) System. First, the paper explains how a Wireless Body Area
      Network (WBAN) that captures data from two sensors corresponding to arterial
      pressure and heart rate is designed. Second, this paper illustrates how data
      collected by the WBAN are transmitted to a cloud storage service. It is worth
      mentioning that this cloud service allows the data to be stored in a persistent
      way on an online database system. Finally, the paper describes, how the data
      stored in the cloud service are sent to the Indivo PHR System, where they are
      registered and charted for future revision by health professionals. The research
      demonstrated the feasibility of implementing WBAN networks for the acquisition of
      clinical data, and particularly for the use of Web technologies and standards to
      provide interoperability with PHR Systems at technical and syntactic levels. 

PMID- 24851978
TI  - End-to-End Encryption for Personal Telehealth Systems.
AB  - Data from personal health devices is expected to be an important part of
      personalized care in future, but communication frameworks for such data create
      new challenges for security and privacy. Continua Health Alliance has been very
      active and successful in defining guidelines and a reference architecture for
      transmitting personal health device data based on well-known international
      standards. But looking at the security definitions, the concepts are still facing
      open issues and weaknesses like identity management or missing end-2end (E2E)
      encryption. This paper presents an approach for an E2E encryption framework based
      on Continua's reference architecture and the underlying base standards. It
      introduces the basic process and proposes necessary extensions to the
      architecture as well as to the standardized protocols of ISO/IEEE 11073 and HL7
      version 2. 

PMID- 24851977
TI  - Trust Information and Privacy Policies - Enablers for pHealth and Ubiquitous
      Health.
AB  - pHealth occurs in uncontrolled and unsecure environment where predefined
      organizational trust does not exist. To be accepted by users, pHealth requires a
      privacy model where privacy is a personal property, i.e., a person can perform
      own will and define policies which regulate how personal health information (PHI)
      is used. Privacy and trust are interconnected concepts. Therefore, before
      beginning to use pHealth services, the person needs practical and reliable
      information that enables her or him to determine the trustworthiness level of
      services. To avoid the use of blind trust, organizations, researchers,
      policymakers, and standardization organizations have proposed the use of dynamic
      context-aware policies for privacy management in pHealth. To make meaningful
      privacy decision, a person should understand the impact of selected policy rules
      on the processing of PHI in different situations. In this paper, the use of
      computational trust information for defining privacy polies and reducing their
      number is proposed. A trust value and understandable trust attributes enable a
      person to tailor privacy policies requested for trustworthy use of pHealth
      services. Trust attributes proposed are derived from privacy concerns existing in
      open ubiquitous environment. These attributes also force pHealth services
      providers to publish information needed for trust calculation and in this way to
      support openness and transparency. 

PMID- 24851979
TI  - Towards Assisted Moderation in Online Healthcare Social Networks: Improving Trust
      in YouTube Searches.
AB  - Moderation of content in online Health Social Networks (HSN) is critical because
      information is not only published and produced by experts or health
      professionals, but also by users of that information. The objective of this paper
      is to propose a semi-automatic moderation Web Service for assessing the quality
      (trustworthiness) of health-related videos published on the YouTube social
      network. The service is relevant for moderators or community managers, who get
      enabled to control the quality of videos published on their online HSN sites. The
      HealthTrust metric was selected as the metric to be implemented in the service in
      order to support the assessment of trustworthiness of videos in Online HSN. The
      service is a RESTful service which can be integrated into open source Virtual
      Social Network Platforms, therefore improving trust in the process of searching
      and publishing content extracted from YouTube. A preliminary pilot evaluation in
      a simple use case demonstrated that the relevance of videos retrieved using the
      moderation service was higher compared to the relevance of the videos retrieved
      using the YouTube search engine. 

PMID- 24851981
TI  - Applying open source data visualization tools to standard based medical data.
AB  - Presentation of medical data in personal health records (PHRs) requires flexible
      platform independent tools to ensure easy access to the information. Different
      backgrounds of the patients, especially elder people require simple graphical
      presentation of the data. Data in PHRs can be collected from heterogeneous
      sources. Application of standard based medical data allows development of generic
      visualization methods. Focusing on the deployment of Open Source Tools, in this
      paper we applied Java Script libraries to create data presentations for standard
      based medical data. 

PMID- 24851982
TI  - Evaluation study for a multi-user oriented medical data visualization method.
AB  - The chosen evaluation concept is based the Guideline for Good Evaluation Practice
      in Health Informatics (GEP-HI). The stages of the study were identified. Each
      stage got a detailed description. We also identified the participants and their
      required qualifications and responsibilities. The developed evaluation concept
      was used for the evaluation study of the developed medical data visualization
      method. The study was performed in Tomsk, Russia. This helped to involve more
      doctors and patients to the study. This also facilitated the involvement of
      patients, because they have already the experience of using patients' portal. 

PMID- 24851983
TI  - Embedded sensor systems for health - providing the tools in future healthcare.
AB  - Wearable, embedded sensor systems for health applications are foreseen to be
      enablers in the future healthcare. They will provide ubiquitous monitoring of
      multiple parameters without restricting the person to stay at home or in the
      hospital. By following trend changes in the health status, early deteriorations
      will be detected and treatment can start earlier. Also health prevention will be
      supported. Such future healthcare requires technology development, including
      miniaturized sensors, smart textiles and wireless communication. The tremendous
      amount of data generated by these systems calls for both signal processing and
      decision support to guarantee the quality of data and avoid overflow of
      information. Safe and secure communications have to protect the integrity of the
      persons monitored. 

PMID- 24851984
TI  - The ELF@Home project: Elderly sELF-care based on sELF-check of health conditions
      and sELF-fitness at home.
AB  - The ELF@Home project is a research and innovation project running from June
      1<sup>st</sup> 2013 to May 31<sup>st</sup> 2016 and co-funded by the Ambient
      Assisted Living Joint Programme (AAL JP) and National Authorities in Spain,
      Sweden and Germany. The ELF@Home project relies on the use of the proven
      advantages of elderly fitness to develop a self-care solution based on self-check
      of health conditions and self-fitness at home. The project uses information and
      communication technologies (ICT) to build an autonomous fitness system targeting
      healthy or pre-frail elderly people aged over 65 and living independently at
      home. 

PMID- 24851985
TI  - Design and implementation of a personal health record system for diabetes
      mellitus type 2 monitoring.
AB  - The objective of this paper is to describe the design and implementation of a
      Personal Health Record System (PHR-S) for supporting monitoring of blood glucose
      in diabetes mellitus type 2 patients. The paper describes a survey applied in
      order to elicit the specific ICT needs of Diabetes Mellitus Type 2 patients.
      Based on the requirements, a web application "GlucoseDataManager" was implanted
      and integrated into a local deployed IndivoHealth PHR-S platform. 

PMID- 24851986
TI  - The impact of computerized decision aid on mode of delivery - a study protocol.
AB  - The paper describes the design of computerized decision aid (DA) and a protocol
      for a cluster randomized controlled trial to study the effects of computerized DA
      on decisional conflict and knowledge of pregnant Iranian women pertaining to the
      mode of delivery: Caesarean section vs. vaginal delivery. 

PMID- 24851987
TI  - Accuracy in pedometers: dependent on the technology for measurement?
AB  - Today, there are a variety of pedometers available based on different
      technologies. The aim of this study was to investigate step measurement accuracy
      regarding two different pedometer technologies, spring-suspended lever arm and
      accelerometers, in six walking environments, compared to a reference method.
      Descriptive data indicates that the spring-suspended lever arm pedometer had the
      largest SD and underestimated the steps in five out of six walking environments.
      The ANOVA showed that both pedometer technologies performed accurate measurements
      in one of the walking environments. However, none of the pedometer technologies
      performed accurate step measurements in all six walking environments. 

PMID- 24851988
TI  - A wireless sensor insole for collecting gait data.
AB  - This paper presents the status of the EU project WIISEL - Wireless Insole for
      Independent and Safe Elderly Living, with the focus on sensors and wireless
      communications. Pressure and inertial sensors are embedded into insoles and a
      smartphone collects data utilizing Bluetooth Low Energy. 

PMID- 24851989
TI  - Personal health systems research--charting the European landscape.
AB  - Personal Health Systems (PHS) open new ways of providing continuous, quality
      controlled and personalized health services to empowered individuals and require
      the emergence of novel cross-disciplinary innovation partnerships. We analyzed
      the European PHS research and innovation landscape with the ultimate goal of a
      better understanding of mismatches between the potential of, and need for, PHS.
      The results of network analysis indicate a dynamic but fragmented PHS innovation
      landscape in Europe. In addition to excellent technological solutions, PHS
      implementation also needs a multi-stakeholder process of service system
      innovation to reach ambitious aims in the future. 

PMID- 24851993
TI  - Genetic parameters for feed efficiency and body weight traits in Japanese quail.
AB  - 1. The objectives of the present study were to estimate heritability and genetic
      correlations for feed efficiency and body weight (BW) in Japanese quail. 2.
      Recorded traits during different weeks of the growing period were BW from hatch
      to 35 d, feed intake (FI), feed conversion ratio (FCR) and residual feed intake
      (RFI) from hatch to 28 d of age. 3. Genetic parameters were estimated by
      restricted maximum likelihood method using ASREML software. The results showed
      that heritability estimates for BW ranged from 0.11 to 0.22, and maternal
      permanent environmental effect was the highest at hatch (0.45). FCR, RFI and FI
      showed moderate heritabilities ranging from 0.13 to 0.40. 4.Genetic correlations
      of BW28 with FI0-28 (0.88) and RFI0-28 (0.1) and genetic correlation of FI0-28
      with FCR0-28 (0.13) and RFI0-28 (0.52) were positive. A negative genetic
      correlation was found between BW28 and FCR0-28 (-0.49). There was a high positive
      genetic correlation (0.67) between RFI0-28 and FCR0-28. 5. In conclusion,
      selection for increased BW and reduced FI in a selection index could be
      recommended to improve feed efficiency traits including FCR and RFI in Japanese
      quail.

PMID- 24851994
TI  - Modeling and simulation of the transient response of temperature and relative
      humidity sensors with and without protective housing.
AB  - Based on the necessity for enclosure protection of temperature and relative
      humidity sensors installed in a hostile environment, a wind tunnel was used to
      quantify the time that the sensors take to reach equilibrium in the environmental
      conditions to which they are exposed. Two treatments were used: (1) sensors with
      polyvinyl chloride (PVC) enclosure protection, and (2) sensors with no enclosure
      protection. The primary objective of this study was to develop and validate a 3-D
      computational fluid dynamics (CFD) model for analyzing the temperature and
      relative humidity distribution in a wind tunnel using sensors with PVC enclosure
      protection and sensors with no enclosure protection. A CFD simulation model was
      developed to describe the temperature distribution and the physics of mass
      transfer related to the airflow relative humidity. The first results demonstrate
      the applicability of the simulation. For verification, a sensor device was
      successfully assembled and tested in an environment that was optimized to ensure
      fast change conditions. The quantification setup presented in this paper is thus
      considered to be adequate for testing different materials and morphologies for
      enclosure protection. The results show that the boundary layer flow regime has a
      significant impact on the heat flux distribution. The results indicate that the
      CFD technique is a powerful tool which provides a detailed description of the
      flow and temperature fields as well as the time that the relative humidity takes
      to reach equilibrium with the environment in which the sensors are inserted. 

PMID- 24851995
TI  - Titanium dioxide crystals with tailored facets.

PMID- 24851996
TI  - Uncovering the self-assembly of DNA nanostructures by thermodynamics and
      kinetics.
AB  - CONSPECTUS: DNA nanotechnology is one of the most flourishing interdisciplinary
      research fields. DNA nanostructures can be designed to self-assemble into a
      variety of periodic or aperiodic patterns of different shapes and length scales.
      They can be used as scaffolds for organizing other nanoparticles, proteins, and
      chemical groups, leveraging their functions for creating complex bioinspired
      materials that may serve as smart drug delivery systems, in vitro or in vivo
      biomolecular computing platforms, and diagnostic devices. Achieving optimal
      structural features, efficient assembly protocols, and precise functional group
      positioning and modification requires a thorough understanding of the
      thermodynamics and kinetics of the DNA nanostructure self-assembly process. The
      most common real-time measurement strategies include monitoring changes in UV
      absorbance based on the hyperchromic effect of DNA, and the emission signal
      changes of DNA intercalating dyes or covalently conjugated fluorescent dyes/pairs
      that accompany temperature dependent structural changes. Thermodynamic studies of
      a variety of DNA nanostructures have been performed, from simple double stranded
      DNA formation to more complex origami assembly. The key parameters that have been
      evaluated in terms of stability and cooperativity include the overall dimensions,
      the folding path of the scaffold, crossover and nick point arrangement, length
      and sequence of single strands, and salt and ion concentrations. DNA tile-tile
      interactions through sticky end hybridization have also been analyzed, and the
      steric inhibition and rigidity of tiles turn out to be important factors. Many
      kinetic studies have also been reported, and most are based on double stranded
      DNA formation. A two-state assumption and the hypothesis of several intermediate
      states have been applied to determine the rate constant and activation energy of
      the DNA hybridization process. A few simulated models were proposed to represent
      the structural, mechanical, and kinetic properties of DNA hybridization. The
      kinetics of strand displacement reactions has also been studied as a special case
      of DNA hybridization. The thermodynamic and kinetic characteristics of DNA
      nanostructures have been exploited to develop rapid and isothermal annealing
      protocols. It is conceivable that a more thorough understanding of the DNA
      assembly process could be used to guide the structural design process and
      optimize the conditions for assembly, manipulation, and functionalization, thus
      benefiting both upstream design and downstream applications.

PMID- 24851997
TI  - Platelets for neonatal transfusion - study 2: a randomised controlled trial to
      compare two different platelet count thresholds for prophylactic platelet
      transfusion to preterm neonates.
AB  - INTRODUCTION: Neonatal thrombocytopenia is a common and important clinical
      problem in preterm neonates. A trial assessing clinically relevant outcomes in
      relation to the different platelet count thresholds used to trigger transfusion
      has never been undertaken in preterm neonates with severe thrombocytopenia.
      OBJECTIVES: Platelets for Neonatal Transfusion - Study 2 (PlaNeT-2) aims to
      assess whether a higher prophylactic platelet transfusion threshold is superior
      to the lower thresholds in current standard practice in reducing the proportion
      of patients who have a major bleed or die up to study day 28. METHODS: PlaNeT-2
      is a two-stage, randomised, parallel-group, superiority trial. PlaNet-2 compares
      clinical outcomes in preterm neonates (<34 weeks' gestation at birth) randomised
      to receive prophylactic platelet transfusions to maintain platelet counts at or
      above either 25 * 10(9)/l or 50 * 10(9)/l. The primary outcome measure is the
      proportion of patients who either die or experience a major bleed up to and
      including study day 28. A total of 660 infants will be randomised. RESULTS AND
      CONCLUSIONS: This trial will help define optimal platelet transfusion support for
      severely thrombocytopenic preterm neonates by evaluating the risks and benefits
      of two different prophylactic neonatal platelet transfusion thresholds.

PMID- 24851998
TI  - The problem of increasing maternal morbidity: integrating normality and risk in
      maternity care in the United States.

PMID- 24852001
TI  - The role of the institutional review board in public health research: the
      position of the Journal of Public Health Management and Practice.

PMID- 24852002
TI  - Medicare claims data as public use files: a new tool for public health
      surveillance.
AB  - Claims data are an important source of data for public health surveillance but
      have not been widely used in the United States because of concern with personally
      identifiable health information and other issues. We describe the development and
      availability of a new set of public use files created using de-identified health
      care claims for fee-for-service Medicare beneficiaries, including individuals 65
      years and older and individuals with disabilities younger than 65 years, and
      their application as tools for public health surveillance. We provide an overview
      of these files and their attributes; a review of beneficiary de-identification
      procedures and implications for analysis; a summary of advantages and limitations
      for use of the public use files for surveillance, alone and in combination with
      other data sources; and discussion and examples of their application for public
      health surveillance using examples that address chronic conditions monitoring,
      hospital readmissions, and prevalence and expenditures in diabetes care.

PMID- 24852003
TI  - Local health departments and billing for clinical services.

PMID- 24852004
TI  - Public health's role in driving down the misuse of prescription drugs: 15 * 15.

PMID- 24852005
TI  - Bottom-up proteomics of Escherichia coli using dynamic pH junction
      preconcentration and capillary zone electrophoresis-electrospray ionization
      tandem mass spectrometry.
AB  - We report the use of the dynamic pH junction based capillary zone electrophoresis
      electrospray ionization-tandem mass spectrometry (CZE-ESI-MS/MS) for bottom-up
      proteomics with an electrokinetically pumped sheath-flow nanospray capillary
      electrophoresis-mass spectrometry (CE-MS) interface and both LTQ-XL and LTQ
      Orbitrap-Velos mass spectrometers. Conventional injection of 20 nL of a 1 mg/mL
      BSA digest identified 37 peptides and produced 66% sequence coverage. In
      contrast, pH junction injection of 130 nL (or larger) of a 0.05 mg/mL BSA digest
      identified 40 peptides and produced 70% coverage using a pH 6.5 sample buffer and
      the LTQ. A 20 nL conventional injection of a 1 mg/mL Escherichia coli digest
      identified 508 peptides and 199 proteins with the LTQ. A 400 nL pH junction
      injection of a 0.1 mg/mL E. coli digest identified 527 peptides and 179 proteins
      with the LTQ. Triplicate technical replicates of a 0.01 mg/mL sample with 400-nL
      injection volume using a pH junction identified 288 +/- 9 peptides and 121 +/- 5
      proteins with the LTQ. There was outstanding concordance in migration time
      between the pH junction and normal injection. The pH junction produced narrower
      peaks and significant concentration for all but the most acidic components in the
      sample. Compared with the conventional stacking method, the pH junction method
      can generate comparable performance for small injection volume (20 nL) and
      significantly better concentration performance for a large injection volume (200
      nL). We also applied the pH junction to three intact standard proteins and
      observed a >10* increase in peak intensity compared to conventional injection. 

PMID- 24852007
TI  - A reference for ductus venosus blood flow at 11-13+6 weeks of gestation.
AB  - OBJECTIVE: To establish reference ranges for ductus venosus (DV) blood flow
      assessment obtained transabdominally at 11-13(+6) weeks of gestation. METHODS: A
      cross-sectional study was conducted on singleton pregnancies with a crown-rump
      length (CRL) ranging from 45 to 84 mm, normal fetus, and subsequent newborn birth
      weight appropriate for gestational age. Measurements of DV Doppler variables were
      performed by experienced sonographers: peak velocity during ventricular systole
      (S-wave) and diastole (D-wave), nadir during atrial contraction (A-wave), time
      averaged maximum velocity (TAmax), pulsatility index for veins (PIV), and peak
      velocity index for veins (PVIV). RESULTS: A total of 304 fetuses were included.
      The mean CRL was 60.7 +/- 7.2 mm (range: 45.9-75.5). The mean nuchal translucency
      measurement was 1.4 +/- 0.4 mm. The S-wave, D-wave, A-wave, and TAmax values
      varied significantly with gestational age (p < 0.05) and regression models were
      constructed for each variable. The remaining variables, systolic/atrial wave
      ratio, preload index, PVIV, and PIV, did not vary significantly with gestational
      age within this CRL range. CONCLUSION: Reference ranges for DV Doppler assessment
      were established in normal fetuses. These ranges may be a useful tool for
      evaluation of anueploidy and fetal cardiac function.

PMID- 24852006
TI  - PCR amplification of repetitive DNA: a limitation to genome editing technologies
      and many other applications.
AB  - Designer transcription-activator like effectors (TALEs) is a promising technology
      and made it possible to edit genomes with higher specificity. Such specific
      engineering and gene regulation technologies are also being developed using RNA
      binding proteins like PUFs and PPRs. The main feature of TALEs, PUFs and PPRs is
      their repetitive DNA/RNA-binding domains which have single nucleotide binding
      specificity. Available kits today allow researchers to assemble these repetitive
      domains in any combination they desire when generating TALEs for gene targeting
      and editing. However, PCR amplifications of such repetitive DNAs are highly
      problematic as these mostly fail, generating undesired artifact products or
      deletions. Here we describe the molecular mechanisms leading to these artifacts.
      We tested our models also in plasmid templates containing one copy versus two
      copies of GFP-coding sequence arranged as either direct or inverted repeats. Some
      limited solutions in amplifying repetitive DNA regions are described. 

PMID- 24852008
TI  - Management and decision-making process leading to coronary angiography and
      revascularization in octogenarians with coronary artery disease: Insights from a
      large single-center registry.
AB  - AIMS: Cardiovascular diseases remain the most common cause of death in older
      adults. Guidelines state that advanced age alone should not limit the use of
      invasive therapy. However, coronary angiograms and subsequent revascularization
      are often not carried out in octogenarians. The benefit/risk balance of an
      invasive strategy and the decision-making process are not clearly defined. The
      aim of the present study was to assess the decision-making process, and the in
      hospital and long-term mortality based on the clinical presentation, the
      diagnostic approach (coronary angiogram or conservative) and the therapeutic
      management (revascularization or not). METHODS: The present study was a single
      center retrospective analysis. RESULTS: A total of 522 patients aged >=80 years,
      with a diagnosis of coronary disease were included from 2003 to 2009. The mean
      age was 82 +/- 2.6 years. A total of 195 of 522 (37%) presented with a ST segment
      elevation myocardial infarction (STEMI). A coronary angiogram was carried out in
      316 patients (60.5%) and 71% were treated by percutaneous coronary
      revascularization. A total of 39.5% were considered ineligible for a coronary
      angiogram due to cardiological reasons or comorbidities. Excluding cardiogenic
      shock, overall in-hospital mortality was 4.9%. Clinical presentation strongly
      influenced both in-hospital and 6-month mortality rates (cardiogenic shock 20%
      and 28.7%, stable angina 1% and 4.1%, respectively, P < 0.001). Long-term
      mortality was reduced in the coronary angiography arm compared with the
      conservative group (14.3% vs 20.9%, P = 0.04) whether or not revascularization
      was carried out. CONCLUSION: In the present study, in octogenarians, long-term
      mortality was lower in the group of patients who underwent a coronary angiogram,
      regardless of revascularization. The selection process for coronary angiography
      and angioplasty was mostly influenced by the existence of age-associated
      comorbidities. Risk prediction models are required to reduce age-dependent
      biases.

PMID- 24852010
TI  - Pseudorandomness of gene expression: a new evo-devo theory of ageing.
AB  - In contrast to the first part of life (development), ageing appears to be under
      less strict genetic control. The precise timing of events so characteristic of
      development seems to loosen its grasp, while stochastic and environmental factors
      seem to become the dominant force. Evolutionary theories put forward a decreasing
      evolutionary pressure over the course of life as the reason behind this pattern,
      yet dissenting views on ageing as a genetically programmed process linger. In
      this paper we address this dissent by presenting insights from an artificial
      evolutionary-developmental system, ET, and propose a new evo-devo theory of
      ageing-a theory that sees ageing as a continuation of development in the
      postreproductive period. In this theory both development and ageing are under
      genetic control. Nonetheless, while gene expression patterns that drive
      development are optimised by evolution, patterns that drive ageing are not
      optimised, because evolutionary pressure decreases with age. For these reasons,
      during ageing the changes orchestrated by genes are "pseudorandom"- deterministic
      but erratic-and their effects on an individual's health are more likely to be
      detrimental than beneficial. As such, they contribute to the continuous
      deterioration of bodily functions that characterise ageing. 

PMID- 24852009
TI  - Range-wide latitudinal and elevational temperature gradients for the world's
      terrestrial birds: implications under global climate change.
AB  - Species' geographical distributions are tracking latitudinal and elevational
      surface temperature gradients under global climate change. To evaluate the
      opportunities to track these gradients across space, we provide a first baseline
      assessment of the steepness of these gradients for the world's terrestrial birds.
      Within the breeding ranges of 9,014 bird species, we characterized the spatial
      gradients in temperature along latitude and elevation for all and a subset of
      bird species, respectively. We summarized these temperature gradients globally
      for threatened and non-threatened species and determined how their steepness
      varied based on species' geography (range size, shape, and orientation) and
      projected changes in temperature under climate change. Elevational temperature
      gradients were steepest for species in Africa, western North and South America,
      and central Asia and shallowest in Australasia, insular IndoMalaya, and the
      Neotropical lowlands. Latitudinal temperature gradients were steepest for
      extratropical species, especially in the Northern Hemisphere. Threatened species
      had shallower elevational gradients whereas latitudinal gradients differed little
      between threatened and non-threatened species. The strength of elevational
      gradients was positively correlated with projected changes in temperature. For
      latitudinal gradients, this relationship only held for extratropical species. The
      strength of latitudinal gradients was better predicted by species' geography, but
      primarily for extratropical species. Our findings suggest threatened species are
      associated with shallower elevational temperature gradients, whereas steep
      latitudinal gradients are most prevalent outside the tropics where fewer bird
      species occur year-round. Future modeling and mitigation efforts would benefit
      from the development of finer grain distributional data to ascertain how these
      gradients are structured within species' ranges, how and why these gradients vary
      among species, and the capacity of species to utilize these gradients under
      climate change. 

PMID- 24852011
TI  - Cosmological immortality: how to eliminate aging on a universal scale.
AB  - The death of our universe is as certain as our individual death. Some
      cosmologists have elaborated models which would make the cosmos immortal. In this
      paper, I examine them as cosmological extrapolations of immortality narratives
      that civilizations have developed to face death anxiety. I first show why
      cosmological death should be a worry, then I briefly examine scenarios involving
      the notion of soul or resurrection on a cosmological scale. I discuss in how far
      an intelligent civilization could stay alive by engaging in stellar, galactic and
      universal rejuvenation. Finally, I argue that leaving a cosmological legacy via
      universe making is an inspiring and promising narrative to achieve cosmological
      immortality. 

PMID- 24852012
TI  - The pursuit of longevity - the bringer of peace to the middle East.
AB  - Despite the common apprehensions regarding the aging population, this work aims
      to argue, on both deontological and utilitarian moral grounds, that any increase
      in general life-expectancy will be beneficial for the Middle East, countering the
      common fears associated with this increase. A set of ethical arguments concerning
      increasing longevity is presented, from both the deontological and utilitarian
      perspective. A wide selection of economic, psychological, demographic and
      epidemiological literature and databases is analyzed to determine common
      correlates of extended longevity. On the deontological grounds, the value of
      extended longevity is derived from the value of life preservation, regardless of
      its term. On the utilitarian grounds, the value of extended longevity is
      demonstrated by its correlation with further human values, such as education
      level and intellectual activity, economic prosperity, equality, solidarity and
      peacefulness. With the common apprehensions of stagnation and scarcity due to
      life extension found wanting, the pursuit of longevity by the population can be
      seen as a cross-cultural and cross-generational good. Though the current study
      mainly refers to sources and data relevant to the Middle East, a similar pro
      longevity argument can be also made for other cultural contexts. In view of its
      numerous benefits, normatively, the goal of longevity should be set clearly and
      openly by the society, and actively pursued, or at least discussed, in academia,
      the political system and broader public. 

PMID- 24852013
TI  - An evolutionary and genomic approach to challenges and opportunities for
      eliminating aging.
AB  - While solutions to major scientific and medical problems are never perfect or
      complete, it is still reasonable to delineate cases where both have been
      essentially solved. For example, Darwin's theory of natural selection provides a
      successful solution to the problem of biological adaptation, while the germ
      theory of infection solved the scientific problem of contagious disease. Likewise
      in the context of medicine, we have effectively solved the problem of contagious
      disease, reducing it to a minor cause of death and disability for almost everyone
      in countries with advanced medicine and adequate resources. Evolutionary
      biologists claim to have solved the scientific problem of aging: we explain it
      theoretically using Hamilton's forces of natural selection; in experimental
      evolution we readily manipulate the onset, rate, and eventual cessation of aging
      by manipulating these forces. In this article, we turn to the technological
      challenge of solving the medical problem of aging. While we feel that the broad
      outlines of such a solution are clear enough starting from the evolutionary
      solution to the scientific problem of aging, we do not claim that we can give a
      complete or exhaustive plan for medically solving the problem of aging. But we
      are confident that biology and medicine will effectively solve the problem of
      aging within the next 50 years, providing Hamiltonian lifestyle changes, tissue
      repair, and genomic technological opportunities are fully exploited in public
      health practices, in medical practice, and in medical research, respectively. 

PMID- 24852014
TI  - Evolutionary orthodoxy: how and why the evolutionary theory of aging went astray.
AB  - Prevailing ideas of how aging evolved are a poor fit with the picture of aging
      that is developing from genetics labs and breeding experiments. Nevertheless, the
      community of theorists is reluctant to consider alternate approaches because the
      differences are profound, calling into question much of the standard methodology
      of Population Genetics. (At stake is not the legacy of Darwin, but the particular
      model of Darwinian selection that has dominated the field of research since the
      middle of the 20th Century). This model may be a historic artifact, arising from
      a time before computers, when a premium was placed on equations that could be
      solved analytically. The standard Population Genetic model gained credibility
      through agreement with laboratory experiments that were designed to realize the
      assumptions of the model, rather than to mirror conditions in the natural world.
      Models of evolution based on pure individual selection or inclusive fitness
      cannot explain the basic phenomenology of aging. Aging is not the only area of
      conflict, however. Other areas which present difficulties for the standard model
      include the origin of sex, the maintenance of diversity, the basis of
      evolvability (including hierarchical structure of the genome), occasional
      persistence of eusociality without close relatedness, and many examples of strong
      altruism. From many corners of the field, creative and visionary biologists are
      calling for a re-thinking of the fundamental mechanisms of natural selection. 

PMID- 24852015
TI  - The concept of phenoptosis and its usefulness for controlling aging.
AB  - Aging is generally interpreted according to two opposing paradigms: 1) as a non
      adaptive phenomenon, caused by the age-related failure of homeostatic mechanisms;
      2) as a specific function, favored by natural selection, which determines the
      self-destruction of the organism, namely explaining aging as phenoptosis. This
      interpretation requires genetically determined and regulated age-specific
      mechanisms, now well documented by an impressive and growing scientific evidence.
      It follows that, in principle, aging is modifiable even up to the condition,
      already existing for many species, of "negligible senescence", alias unlimited
      longevity. 

PMID- 24852016
TI  - Human evolution, life history theory, and the end of biological reproduction.
AB  - Throughout primate history there have been three major life history transitions
      towards increasingly delayed sexual maturation and biological reproduction, as
      well as towards extended life expectancy. Monkeys reproduce later and live longer
      than do prosimians, apes reproduce later and live longer than do monkeys, and
      humans reproduce later and live longer than do apes. These life history
      transitions are connected to increased encephalization. During the last life
      history transition from apes to humans, increased encephalization co-evolved with
      increased dependence on cultural knowledge for energy acquisition. This led to a
      dramatic pressure for more energy investment in growth over current biological
      reproduction. Since the industrial revolution socioeconomic development has led
      to even more energy being devoted to growth over current biological reproduction.
      I propose that this is the beginning of an ongoing fourth major primate life
      history transition towards completely delayed biological reproduction and an
      extension of the evolved human life expectancy. I argue that the only fundamental
      difference between this primate life history transition and previous life history
      transitions is that this transition is being driven solely by cultural evolution,
      which may suggest some deeper evolutionary transition away from biological
      evolution is already in the process of occurring. 

PMID- 24852017
TI  - Reversal of informational entropy and the acquisition of germ-like immortality by
      somatic cells.
AB  - We live within an increasingly technological, information-laden environment for
      the first time in human evolution. This subjects us (and will continue to subject
      us in an accelerating fashion) to an unremitting exposure to 'meaningful
      information that requires action'. Directly dependent upon this new environment
      are novel evolutionary pressures, which can modify existing resource allocation
      mechanisms and may eventually favour the survival of somatic cells (particularly
      neurons) at the expense of germ line cells. In this theoretical paper I argue
      that persistent, structured information-sharing in both virtual and real domains,
      leads to increased biological complexity and functionality, which reflects upon
      human survival characteristics. Certain biological immortalisation mechanisms
      currently employed by germ cells may thus need to be downgraded in order to
      enable somatic cells to manage these new energy demands placed by our modern
      environment. Relevant concepts from a variety of disciplines such as the
      evolution of complex adaptive systems, information theory, digital hyper
      connectivity, and cell immortalisation will be reviewed. Using logical, though
      sometimes speculative arguments, I will attempt to describe a new biology. A
      biology not driven by sex and reproduction but by information and somatic
      longevity. 

PMID- 24852018
TI  - Cybernetic principles of aging and rejuvenation: the buffering- challenging
      strategy for life extension.
AB  - Aging is analyzed as the spontaneous loss of adaptivity and increase in fragility
      that characterizes dynamic systems. Cybernetics defines the general regulatory
      mechanisms that a system can use to prevent or repair the damage produced by
      disturbances. According to the law of requisite variety, disturbances can be held
      in check by maximizing buffering capacity, range of compensatory actions, and
      knowledge about which action to apply to which disturbance. This suggests a
      general strategy for rejuvenating the organism by increasing its capabilities of
      adaptation. Buffering can be optimized by providing sufficient rest together with
      plenty of nutrients: amino acids, antioxidants, methyl donors, vitamins,
      minerals, etc. Knowledge and the range of action can be extended by subjecting
      the organism to an as large as possible variety of challenges. These challenges
      are ideally brief so as not to deplete resources and produce irreversible damage.
      However, they should be sufficiently intense and unpredictable to induce an
      overshoot in the mobilization of resources for damage repair, and to stimulate
      the organism to build stronger capabilities for tackling future challenges. This
      allows them to override the trade-offs and limitations that evolution has built
      into the organism's repair processes in order to conserve potentially scarce
      resources. Such acute, "hormetic" stressors strengthen the organism in part via
      the "order from noise" mechanism that destroys dysfunctional structures by
      subjecting them to strong, random variations. They include heat and cold,
      physical exertion, exposure, stretching, vibration, fasting, food toxins, micro
      organisms, environmental enrichment and psychological challenges. The proposed
      buffering-challenging strategy may be able to extend life indefinitely, by
      forcing a periodic rebuilding and extension of capabilities, while using the
      Internet as an endless source of new knowledge about how to deal with
      disturbances. 

PMID- 24852019
TI  - Validating the operational bias and hypothesis of universal exponent in landslide
      frequency-area distribution.
AB  - The exponent decay in landslide frequency-area distribution is widely used for
      assessing the consequences of landslides and with some studies arguing that the
      slope of the exponent decay is universal and independent of mechanisms and
      environmental settings. However, the documented exponent slopes are diverse and
      hence data processing is hypothesized for this inconsistency. An elaborated
      statistical experiment and two actual landslide inventories were used here to
      demonstrate the influences of the data processing on the determination of the
      exponent. Seven categories with different landslide numbers were generated from
      the predefined inverse-gamma distribution and then analyzed by three data
      processing procedures (logarithmic binning, LB, normalized logarithmic binning,
      NLB and cumulative distribution function, CDF). Five different bin widths were
      also considered while applying LB and NLB. Following that, the maximum likelihood
      estimation was used to estimate the exponent slopes. The results showed that the
      exponents estimated by CDF were unbiased while LB and NLB performed poorly. Two
      binning-based methods led to considerable biases that increased with the increase
      of landslide number and bin width. The standard deviations of the estimated
      exponents were dependent not just on the landslide number but also on binning
      method and bin width. Both extremely few and plentiful landslide numbers reduced
      the confidence of the estimated exponents, which could be attributed to limited
      landslide numbers and considerable operational bias, respectively. The diverse
      documented exponents in literature should therefore be adjusted accordingly. Our
      study strongly suggests that the considerable bias due to data processing and the
      data quality should be constrained in order to advance the understanding of
      landslide processes. 

PMID- 24852020
TI  - Convenient detection of HPV virus in a clinical sample using concurrent rolling
      circle and junction probe amplifications.
AB  - Herein we show that two isothermal amplification strategies, rolling circle
      amplification and junction probe strategy, can be used in tandem in the same tube
      under isothermal conditions to detect HPV16 in clinical cervical swabs. It was
      discovered that the prior treatment of the clinical sample with a cocktail of
      restriction endonucleases (REAses) to digest the genomic DNA facilitated the
      isothermal detection assay. 

PMID- 24852021
TI  - BCA2/Rabring7 targets HIV-1 Gag for lysosomal degradation in a tetherin
      independent manner.
AB  - BCA2 (Rabring7, RNF115 or ZNF364) is a RING-finger E3 ubiquitin ligase that was
      identified as a co-factor in the restriction imposed by tetherin/BST2 on HIV-1.
      Contrary to the current model, in which BCA2 lacks antiviral activity in the
      absence of tetherin, we found that BCA2 possesses tetherin-independent antiviral
      activity. Here we show that the N-terminus of BCA2 physically interacts with the
      Matrix region of HIV-1 and other retroviral Gag proteins and promotes their
      ubiquitination, redistribution to endo-lysosomal compartments and, ultimately,
      lysosomal degradation. The targeted depletion of BCA2 in tetherin-expressing and
      tetherin-deficient cells results in a significant increase in virus release and
      replication, indicating that endogenous BCA2 possesses antiviral activity.
      Therefore, these results indicate that BCA2 functions as an antiviral factor that
      targets HIV-1 Gag for degradation, impairing virus assembly and release. 

PMID- 24852023
TI  - Toward autonomous avian-inspired grasping for micro aerial vehicles.
AB  - Micro aerial vehicles, particularly quadrotors, have been used in a wide range of
      applications. However, the literature on aerial manipulation and grasping is
      limited and the work is based on quasi-static models. In this paper, we draw
      inspiration from agile, fast-moving birds such as raptors, that are able to
      capture moving prey on the ground or in water, and develop similar capabilities
      for quadrotors. We address dynamic grasping, an approach to prehensile grasping
      in which the dynamics of the robot and its gripper are significant and must be
      explicitly modeled and controlled for successful execution. Dynamic grasping is
      relevant for fast pick-and-place operations, transportation and delivery of
      objects, and placing or retrieving sensors. We show how this capability can be
      realized (a) using a motion capture system and (b) without external sensors
      relying only on onboard sensors. In both cases we describe the dynamic model, and
      trajectory planning and control algorithms. In particular, we present a
      methodology for flying and grasping a cylindrical object using feedback from a
      monocular camera and an inertial measurement unit onboard the aerial robot. This
      is accomplished by mapping the dynamics of the quadrotor to a level virtual image
      plane, which in turn enables dynamically-feasible trajectory planning for image
      features in the image space, and a vision-based controller with guaranteed
      convergence properties. We also present experimental results obtained with a
      quadrotor equipped with an articulated gripper to illustrate both approaches. 

PMID- 24852024
TI  - Euthanasia for children and young people?
AB  - In February 2014 the Belgian parliament voted to extend the existing euthanasia
      law to cover children under the age of 18. The law sanctions euthanasia for
      children with terminal or incurable conditions who are near death, suffering
      'constant and unbearable pain', and whose parents and health professionals agree
      with the decision. The child also has to be interviewed by a psychologist or
      psychiatrist to ascertain and certify their 'capacity of discernment'. 

PMID- 24852025
TI  - Listening differently to patients can help enhance their experience of care.
AB  - Receiving and responding to timely feedback from patients is a vital component of
      high-quality care. However, this has long been a neglected area, especially for
      people receiving end-of-life services. 

PMID- 24852022
TI  - Scribble modulates the MAPK/Fra1 pathway to disrupt luminal and ductal integrity
      and suppress tumour formation in the mammary gland.
AB  - Polarity coordinates cell movement, differentiation, proliferation and apoptosis
      to build and maintain complex epithelial tissues such as the mammary gland. Loss
      of polarity and the deregulation of these processes are critical events in
      malignant progression but precisely how and at which stage polarity loss impacts
      on mammary development and tumourigenesis is unclear. Scrib is a core polarity
      regulator and tumour suppressor gene however to date our understanding of Scrib
      function in the mammary gland has been limited to cell culture and
      transplantation studies of cell lines. Utilizing a conditional mouse model of
      Scrib loss we report for the first time that Scrib is essential for mammary duct
      morphogenesis, mammary progenitor cell fate and maintenance, and we demonstrate a
      critical and specific role for Scribble in the control of the early steps of
      breast cancer progression. In particular, Scrib-deficiency significantly induced
      Fra1 expression and basal progenitor clonogenicity, which resulted in fully
      penetrant ductal hyperplasia characterized by high cell turnover, MAPK
      hyperactivity, frank polarity loss with mixing of apical and basolateral membrane
      constituents and expansion of atypical luminal cells. We also show for the first
      time a role for Scribble in mammalian spindle orientation with the onset of
      mammary hyperplasia being associated with aberrant luminal cell spindle
      orientation and a failure to apoptose during the final stage of duct
      tubulogenesis. Restoring MAPK/Fra1 to baseline levels prevented Scrib
      hyperplasia, whereas persistent Scrib deficiency induced alveolar hyperplasia and
      increased the incidence, onset and grade of mammary tumours. These findings,
      based on a definitive genetic mouse model provide fundamental insights into
      mammary duct maturation and homeostasis and reveal that Scrib loss activates a
      MAPK/Fra1 pathway that alters mammary progenitor activity to drive premalignancy
      and accelerate tumour progression. 

PMID- 24852026
TI  - The development of national guidelines for the management of radiotherapy-induced
      skin reactions.
AB  - Over 60% of individuals diagnosed with cancer in the UK receive radiotherapy as
      part of their treatment (Department of Health, 2012). Radiotherapy is highly
      effective, and 34-50% of prescribed radiotherapy is given with palliative intent
      to treat symptoms of advanced disease (Hung, 2007). 

PMID- 24852027
TI  - The role of subcutaneous infusion in integrated, patient-centred palliative care.
AB  - The NHS Outcomes Framework (Department of Health (DH), 2010) set out the UK
      Government's plans to reform the NHS to focus more on patient outcomes. 

PMID- 24852028
TI  - Patients' experiences of ongoing palliative chemotherapy for metastatic
      colorectal cancer: a qualitative study.
AB  - BACKGROUND: Colorectal cancer is the second most common cause of cancer death in
      New Zealand. With new chemotherapy regimens, patients with metastatic colorectal
      cancer are now living longer with the condition and its treatment. AIM: This
      study aimed to explore patients' experiences of extended palliative chemotherapy
      for metastatic colorectal cancer. METHODS: A convenience sample of 10 outpatients
      who had been receiving palliative chemotherapy for more than 12 months from a
      teaching hospital and regional cancer centre in New Zealand participated in face
      to-face semi-structured interviews. The data was analysed using a general
      inductive approach. FINDINGS: Three key themes were identified: the importance of
      relationships, presenting a positive face, and life is for living. The importance
      of interpersonal relationships with health professionals and a sense of comradery
      with other chemotherapy patients positively affected the patients' experiences of
      treatment. Positivity was a key coping strategy that also has negative
      implications as patients may not reveal their concerns and needs. CONCLUSION: The
      key to improving the care of people with advanced cancer is understanding their
      experiences of care. Communication between the patient, family, and health-care
      team ensures assumptions that misinterpret attributes of positivity are not made.

PMID- 24852029
TI  - Impact of a legislative framework on quality of end-of-life care and dying in an
      acute hospital in Spain.
AB  - BACKGROUND: In Andalusia, Spain, a legislative framework was put in place in 2010
      to guarantee dignity in dying and quality of care in the last phase of life. AIM:
      The aim of this study was to determine whether health professionals have
      incorporated the requirements of this legislation into their clinical practice
      and whether there have been improvements in decision-making procedures affecting
      the quality of dying in hospitals. METHODS: A cross-sectional analysis was
      carried out in an acute hospital in Andalusia, Spain. Clinical records of
      patients who died in the Costa del Sol Hospital were evaluated before and after
      the new legislative framework was introduced. Participants were all the patients
      aged over 18 years (n=398) who died in 2009 (n=216) or 2011 (n=182) of
      oncological disease or non-oncological chronic disease. Bivariate analyses
      evaluated differences between the two periods and associations among the
      patients' characteristics and the context of care. RESULTS: Provision of
      information on measures to facilitate comfort and the relief of physical
      suffering increased from 15.7% to 22.0%, although this was not significant. There
      was a significant increase in the number of patients who received joint
      counselling in this regard from doctors and nurses, from 0% in 2009 to 7.1% in
      2011. CONCLUSIONS: The minimal changes found 1 year after the implementation of
      the framework confirm that culture change is a lengthy, difficult task that
      cannot be achieved through laws alone.

PMID- 24852030
TI  - Can art therapy reduce death anxiety and burnout in end-of-life care workers? a
      quasi-experimental study.
AB  - BACKGROUND: The need for empathy and the difficulties of coping with mortality
      when caring for the dying and the bereaved can cause psychological, emotional,
      and spiritual strain. OBJECTIVE: The aim of this study was to examine the
      effectiveness of art-therapy-based supervision in reducing burnout and death
      anxiety among end-of-life care workers in Hong Kong. METHODS: Through a quasi
      experimental design, 69 participants enrolled in a 6-week, 18-hour art-therapy
      based supervision group, and another 63 enrolled in a 3-day, 18-hour standard
      skills-based supervision group (n=132). Pre- and post-intervention assessments
      were carried out with three outcome measures: the Maslach Burnout Inventory
      General Survey, the Five Facet Mindfulness Questionnaire, and the Death Attitude
      Profile-Revised. The data was analysed using paired sample t-tests. RESULTS:
      Significant reductions in exhaustion and death anxiety and significant increases
      in emotional awareness were observed for participants in the art-therapy-based
      supervision group. CONCLUSION: This study provides preliminary evidence that art
      therapy-based supervision for end-of-life care workers can reduce burnout by
      enhancing emotional awareness and regulation, fostering meaning-making, and
      promoting reflection on death.

PMID- 24852031
TI  - Nurses' perceptions of proactive palliative care: a Dutch focus group study.
AB  - BACKGROUND: Early identification of pain and other problems is an important
      aspect of palliative care. Although nurses have an important role in palliative
      care, little is known about nurses' perceptions of proactive palliative care.
      OBJECTIVES: This study aimed to explore nurses' perceptions and experiences of
      proactive identification of problems and requirements among patients with
      palliative care needs. METHODS: This was a qualitative study in which 16 nurses
      working in palliative care took part in two focus groups. RESULTS: All of the
      nurses underlined the importance of their early involvement in palliative care.
      Anticipation of possible future problems, advice and information about end-of
      life care and palliative care facilities, and assessment of patients' wishes
      regarding care and preferred place of death were mentioned as important aspects
      of the early identification of problems and needs. Four themes were identified:
      the start of proactive palliative care; communication, support, and guidance;
      advocating for patients; and cooperation with health professionals. CONCLUSIONS:
      Nurses' involvement in proactive palliative care is important in supporting
      patients' palliative care management. Ongoing education, focused on
      multidisciplinary communication and cooperation, professional development, and
      empowerment of nurses, remains of utmost importance.

PMID- 24852032
TI  - Community palliative care clinical nurse specialists: a descriptive study of
      nurse-patient interactions.
AB  - BACKGROUND: With an ageing population and changes to the UK process of
      commissioning health-care services, it is important that the role of the
      community palliative care clinical nurse specialist (CPC-CNS) is better
      understood. AIM: This study aimed to describe CPC-CNS activities during
      interactions with patients. METHODS: Four CPC-CNSs were observed and audio
      recorded during interactions with 34 patients. The data was assessed
      qualitatively using thematic analysis. RESULTS: An enormous breadth of activities
      were observed, within a framework of assessment, planning, intervention, and
      evaluation. Cross-cutting themes were real-time decision making, leadership,
      ability to respond to and coordinate complex and varied situations, and
      communication techniques. Data saturation was not achieved. CONCLUSION: CPC-CNSs
      provide multifaceted care, requiring wide-ranging knowledge to enable them to act
      as liaison points in a complex health service, respond independently to the
      fluctuating needs of patients, and provide effective advance care planning,
      particularly to those with advanced disease, multi-morbidity, and frailty.

PMID- 24852036
TI  - Commensurability-driven structural defects in double emulsions produced with two
      step microfluidic techniques.
AB  - The combination of two drop makers such as flow focusing geometries or ?
      junctions is commonly used in microfluidics to fabricate monodisperse double
      emulsions and novel fluid-based materials. Here we investigate the physics of the
      encapsulation of small droplets inside large drops that is at the core of such
      processes. The number of droplets per drop studied over time for large sequences
      of consecutive drops reveals that the dynamics of these systems are complex: we
      find a succession of well-defined elementary patterns and defects. We present a
      simple model based on a discrete approach that predicts the nature of these
      patterns and their non-trivial scheme of arrangement in a sequence as a function
      of the ratio of the two timescales of the problem, the production times of
      droplets and drops. Experiments validate our model as they concur very well with
      predictions. 

PMID- 24852037
TI  - Comparison of high vs. normal/low protein diets on renal function in subjects
      without chronic kidney disease: a systematic review and meta-analysis.
AB  - BACKGROUND: It was the aim of the present systematic review and meta-analysis to
      investigate the effects of high protein (HP) versus normal/low protein (LP/NP)
      diets on parameters of renal function in subjects without chronic kidney disease.
      METHODS: Queries of literature were performed using the electronic databases
      MEDLINE, EMBASE, and the Cochrane Trial Register until 27th February 2014. Study
      specific weighted mean differences (MD) were pooled using a random effect model
      by the Cochrane software package Review Manager 5.1. FINDINGS: 30 studies
      including 2160 subjects met the objectives and were included in the meta
      analyses. HP regimens resulted in a significantly more pronounced increase in
      glomerular filtration rate [MD: 7.18 ml/min/1.73 m2, 95% CI 4.45 to 9.91,
      p<0.001], serum urea [MD: 1.75 mmol/l, 95% CI 1.13 to 237, p<0.001], and urinary
      calcium excretion [MD: 25.43 mg/24h, 95% CI 13.62 to 37.24, p<0.001] when
      compared to the respective LP/NP protocol. CONCLUSION: HP diets were associated
      with increased GFR, serum urea, urinary calcium excretion, and serum
      concentrations of uric acid. In the light of the high risk of kidney disease
      among obese, weight reduction programs recommending HP diets especially from
      animal sources should be handled with caution.

PMID- 24852038
TI  - Paradoxical changes of retinal nerve fiber layer thickness in uveitic glaucoma.
AB  - IMPORTANCE: Measurement of retinal nerve fiber layer (RNFL) thickness using
      optical coherence tomography can aid in the diagnosis and management of glaucoma.
      We observed a previously unreported phenomenon in eyes with uveitis-associated
      glaucoma in which paradoxical changes in RNFL thickness were noted. OBSERVATIONS:
      Four eyes of 3 patients with uveitis-associated glaucoma had a relatively normal
      RNFL measurement on presentation during periods of active uveitis and raised
      intraocular pressure. Subsequent control of uveitis and intraocular pressure was
      associated with a paradoxical thinning of the RNFL and increased cupping.
      CONCLUSIONS AND RELEVANCE: Normal-appearing measurements of RNFL thickness in
      patients with uveitis should be interpreted cautiously in those with a raised
      intraocular pressure. Physicians should recognize that continued thinning of the
      RNFL and increased cupping, despite good intraocular pressure control in such
      eyes, may be due to resolution of edema of the RNFL.

PMID- 24852040
TI  - Catalytic bond forming reactions promoted by amidinate, guanidinate and
      phosphaguanidinate compounds of magnesium.
AB  - The synthesis and catalytic properties of a series of magnesium compounds
      consisting of monoanionic, N,N'-chelating ligands (N?N = amidinates,
      guanidinates, phosphaguanidinates) is reported. The compounds were synthesized by
      (i) insertion of a carbodiimide into an existing Mg-C or Mg-N bond, or (ii)
      protonolysis of an organomagnesium compound by a neutral pre-ligand. Structural
      analyses of mono- or bis-(chelate) compounds with general formula Mg(N?N)X(L)n
      and Mg(N?N)2(L)n (X = halide, aryloxide, amide; L = Et2O, THF; n = 0, 1 or 2)
      have been performed and the influence that the ligand substituent patterns have
      on the solid-state structures has been probed. Selected examples of the compounds
      were tested as (pre)catalysts for the polymerization of lactide, the dimerization
      of aldehydes and the hydroacetylenation of carbodiimides. 

PMID- 24852039
TI  - Transgenic rice as bioreactor for production of the Candida antarctica lipase B.
AB  - Candida antarctica lipase B (CALB) is a versatile biocatalyst used for a wide
      range of biotransformation. Methods for low cost production of this enzyme are
      highly desirable. Here, we report a mass production method of CALB using
      transgenic rice seeds as the bioreactor. The transgenic rice transformed with the
      CALB gene under the control of the promoter of the rice seed storage protein GT1
      was found to have accumulated a large quantity of CALB in seeds. The transgenic
      line with the highest lipolytic activity reached to 85 units per gram of dry
      seeds. One unit is defined as the amount of lipase necessary to liberate 1 MUmol
      p-nitrophenol from p-nitrophenyl butyrate in 1 min. The rice recombinant lipase
      (rOsCALB) from this line represents 40% of the total soluble proteins in the
      crude seed extracts. The enzyme purified from the rice seeds had an optimal
      temperature of 40  degrees C, and optimal pH of 8.5, similar to that of the
      fermentation products. Test of its conversion ability as a biocatalyst for
      biodiesel production suggested that rOsCALB is functionally identical to the
      fermentation products in its industrial application. 

PMID- 24852042
TI  - Information contributed by meta-analysis in exposure-response modeling:
      application to phase 2 dose selection of guselkumab in patients with moderate-to
      severe psoriasis.
AB  - Ustekinumab, a human immunoglobulin G1 kappa (IgG1kappa) monoclonal antibody that
      binds with high affinity to human interleukin (IL)-12 and IL-23, has been
      approved to treat patients with psoriasis. Guselkumab is a related human IgG1
      monoclonal antibody in clinical development which specifically blocks IL-23. The
      objective of this study was to study the exposure-response relationship of
      guselkumab to guide dose selection for a Phase 2 study in patients with moderate
      to-severe psoriasis. Data were available from a Phase 1 study of 47 healthy
      subjects and 24 patients with psoriasis who received various doses of guselkumab.
      Disease severity was assessed using Psoriasis Area and Severity Index (PASI)
      scores in all studies. Individual pharmacokinetic parameters were derived from
      population pharmacokinetics modeling for the purpose of exposure-response
      modeling to guide dosing regimen selection. A population mechanism-based exposure
      response model of guselkumab was developed to evaluate the association of
      guselkumab dosing with PASI scores using a Type I indirect response model, with
      placebo effect empirically modeled. The model was subsequently updated, first by
      incorporating data from psoriasis patients who received placebo (n = 765) and
      from patients actively treated with ustekinumab 45 or 90 mg (n = 1,230) in two
      ustekinumab Phase 3 trials. Inclusion of this additional ustekinumab data and the
      consequent contributions to specific model components substantially reduced
      uncertainties in all model components except for one parameter. Additional
      sensitivity analyses showed that the dose selection decision was robust to this
      remaining uncertainty. The described approach underscores the importance of
      utilizing all available sources of information in dose selection decisions, along
      with the importance of effective development team interaction. 

PMID- 24852043
TI  - High prevalence of cross-resistance to aminoglycosides in fluoroquinolone
      resistant Escherichia coli clinical isolates.
AB  - BACKGROUND: Multidrug-resistant Escherichia coli, especially a lineage of O25b:H4
      ST131, has increased and spread worldwide. The surveillance of cross-resistance
      of E. coli is necessary. METHODS: Cross-resistance to fluoroquinolones (FQs) and
      aminoglycosides (AGs) was examined in E. coli isolated in Hokkaido Prefecture,
      Japan, between 2008 and 2009. RESULTS: Gentamicin (GEN) resistance was more
      common in FQ-resistant isolates (30/112 strains; 26.8%) than in FQ-susceptible
      isolates (2/100 strains; 2%). The frequency of GEN resistance was similar in two
      groups of FQ-resistant strains, O25b:H4-ST131 genotype (22/87 strains; 25.3%) and
      a group of other FQ-resistant genotypes (8/25 strains; 32.0%). The main AG
      resistance gene was aac(3)-II (87.5% of GEN-resistant strains). The only amikacin
      resistant strain which was FQ resistant carried the aac(6')-Ib-cr gene. CTX-M
      type extended-spectrum beta-lactamase (ESBL) genes were also found in FQ
      resistant strains at a high frequency. However, the number of strains with both
      ESBL and AG-modifying enzyme genes was relatively low (8 strains). CONCLUSION:
      All FQ-resistant strains, not only O25b:H4-ST131, appeared to preferentially
      acquire ESBL genes and/or genes encoding AG-modifying enzymes; however, the
      acquisitions of these genes seemed to occur independently.

PMID- 24852041
TI  - Positron emission tomography diagnostic imaging in multidrug-resistant
      hepatocellular carcinoma: focus on 2-deoxy-2-(18F)Fluoro-D-Glucose.
AB  - Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide.
      Surgical resection and liver transplantation are still the best options for
      treatment. Nevertheless, as the number of patients who may benefit from these
      therapies is limited, alternative therapies have been developed, including
      chemotherapy. However, partly due to the expression of multidrug resistance (MDR)
      proteins, it has been found that HCC is a highly chemoresistant tumor. The major
      family of MDR proteins is the ATP-binding cassette (ABC) transporter superfamily,
      which includes P-glycoprotein (Pgp) and MDR-associated protein 1 (MRP1). Positron
      emission tomography using the radiolabeled analog of glucose, 2-deoxy-2
      ((18)F)fluoro-D-glucose ([(18)F]FDG), has been used in diagnostic imaging of
      various types of tumors. Clinical studies are inconsistent but experimental
      studies have shown that [(18)F]FDG uptake is associated with tumor grade and is
      inversely proportional to Pgp expression in HCC. These studies unveil that
      [(18)F]FDG can be a substrate of Pgp, although that relationship remains unclear.
      This review sums up the relationship between MDR expression in HCC, and
      [(18)F]FDG uptake by tumor cells, showing that this radiopharmaceutical may
      provide a useful tool for the study of chemoresistance in HCC, and that the use
      of this marker may contribute to the therapeutic choice on this highly aggressive
      tumor. 

PMID- 24852048
TI  - [Atypical rhagade of the anal rim].

PMID- 24852049
TI  - Use of ranolazine in patients with stable angina pectoris.
AB  - The current American Heart Association/American College of Cardiology guidelines
      for patients with stable angina pectoris recommend beta-blockers as the initial
      drug therapy for prevention of angina pectoris (class I B indication). Long
      acting nitrates or calcium channel blockers should be prescribed for prevention
      of angina when beta-blockers are contraindicated or not tolerated secondary to
      side effects (class I B indication). Long-acting nitrates or calcium channel
      blockers in combination with beta-blockers should be prescribed for angina
      prevention when initial treatment with beta-blockers is unsuccessful (class I B
      indication). Only sublingual nitroglycerin or nitroglycerin spray should be used
      for immediate relief of angina pectoris (class I B indication). Ranolazine with
      beta-blockers can be used for prevention of angina when initial treatment with
      beta-blockers is not successful (class IIa A indication). If angina persists
      despite treatment with beta-blockers, long-acting nitrates and calcium channel
      blockers, we recommend the addition of ranolazine for prevention of stable angina
      pectoris. This editorial discusses the contemporary role of ranolazine in the
      management of patients with stable angina pectoris.

PMID- 24852050
TI  - Incidence of human Taenia solium larval Infections in an Ecuadorian endemic area:
      implications for disease burden assessment and control.
AB  - BACKGROUND: Human cysticercosis is a zoonotic disease causing severe health
      disorders and even death. While prevalence data become available worldwide,
      incidence rate and cumulative incidence figures are lacking, which limits the
      understanding of the Taenia solium epidemiology. METHODOLOGY/PRINCIPAL FINDINGS:
      A seroepidemiological cohort study was conducted in a south-Ecuadorian community
      to estimate the incidence rate of infection with and the incidence rate of
      exposure to T. solium based on antigen and antibody detections, respectively. The
      incidence rate of infection was 333.6 per 100,000 person-years (95% CI: [8.4
      1,858] per 100,000 person-years) contrasting with a higher incidence rate of
      exposure 13,370 per 100,000 person-years (95% CI: [8,730-19,591] per 100,000
      person-years). The proportion of infected individuals remained low and stable
      during the whole study year while more than 25% of the population showed at least
      one antibody seroconversion/seroreversion during the same time period.
      CONCLUSIONS/SIGNIFICANCE: Understanding the transmission of T. solium is
      essential to develop ad hoc cost-effective prevention and control programs. The
      estimates generated here may now be incorporated in epidemiological models to
      simulate the temporal transmission of the parasite and the effects of control
      interventions on its life cycle. These estimates are also of high importance to
      assess the disease burden since incidence data are needed to make regional and
      global projections of morbidity and mortality related to cysticercosis.

PMID- 24852052
TI  - HLA-B*52:33, a variant of HLA-B*52, discovered in a Taiwanese unrelated
      hematopoietic stem cell donor.

PMID- 24852054
TI  - Impact of psoriasis severity on family income and quality of life.
AB  - BACKGROUND: Psoriasis is a common disease and the costs of its therapy, medical
      care and loss of productivity are a major financial burden for patients and
      society. The financial status of psoriasis patients and its relationship with
      disease severity and quality of life (QoL) remains ill characterized. OBJECTIVE:
      The aim of this study was to assess the economic status of psoriasis patients and
      to investigate its correlation with disease severity and its impact on QoL.
      METHODS: A total of 83 (45 male) psoriasis patients, treated at a Polish
      specialty clinic, were assessed for their financial and employment status. QoL
      was measured with a generic (WHOQOL-BREF) and a skin disease-related QoL
      instrument (dermatology life quality index--DLQI). The effects of demographic and
      clinical variables, including disease severity measured by Psoriasis Area and
      Severity Index (PASI), on the family income of patients were analyzed by multiple
      logistic regression. The mediating effect of family income between PASI and QoL
      was assessed by using the Baron and Kenny's procedure. RESULTS: Patients' family
      income correlate negatively with psoriasis severity (Spearman's rho = -0.356; P <
      0.01). Disease severity in patients with a family income below the social minimum
      was significantly higher (PASI: 20.5 +/- 12.2) than in patients with a higher
      family income (PASI: 11.7 +/- 7.7, P < 0.001). We found that education, disease
      severity and age predict 50% of the variability in family income (P < 0.001).
      Disease severity showed the second strongest impact on income after education (P
      < 0.01). Family income was found to link disease severity to global QoL
      impairment (P < 0.05). CONCLUSION: Disease severity negatively affects the
      financial status of psoriasis patients, which in turn, is a mediator of global
      QoL impairment. Our findings are alarming and call for long-term solutions that
      equalize employment opportunities for patients with psoriasis.

PMID- 24852055
TI  - Mephedrone and other cathinones.
AB  - PURPOSE OF REVIEW: New designer drugs are constantly emerging in the illicit drug
      market and represent a significant health problem. A very popular class comprises
      synthetic cathinones, beta-keto amphetamine analogues, endowed with
      psychostimulant properties. The aim of this review is to discuss the recent
      progress in our understanding of how cathinones act and the health consequences
      of their use. RECENT FINDINGS: Despite being banned, synthetic cathinones are
      still used, especially by certain sub-populations. The recently observed trend to
      supplement psychostimulatory drugs of abuse with mephedrone must be considered
      highly dangerous to the public health. At the molecular level, the drugs act as
      blockers or substrates for monoamine transporter proteins. In animal studies,
      cathinones were found to evoke abuse-related behaviors and to have a negative
      impact on cognitive processes. The increased popularity of mephedrone among men
      who have sex with men with alarming sexual health consequences warrants the
      implementation of new treatments and education/training programs. SUMMARY:
      Synthetic cathinones exert similar, but not identical, effects to
      psychostimulatory drugs of abuse. The use of cathinones may lead to serious
      psychotic, neurological, cardiovascular, and sexual health consequences. Exposure
      to these drugs may result in multiorgan failure and death.

PMID- 24852051
TI  - Antigens for CD4 and CD8 T cells in tuberculosis.
AB  - Tuberculosis (TB), caused by infection with Mycobacterium tuberculosis (MTB),
      represents an important cause of morbidity and mortality worldwide for which an
      improved vaccine and immunodiagnostics are urgently needed. CD4(+) and CD8(+) T
      cells play an important role in host defense to TB. Definition of the antigens
      recognized by these T cells is critical for improved understanding of the
      immunobiology of TB and for development of vaccines and diagnostics. Herein, the
      antigens and epitopes recognized by classically HLA class I- and II-restricted
      CD4(+) and CD8(+) T cells in humans infected with MTB are reviewed.
      Immunodominant antigens and epitopes have been defined using approaches targeting
      particular TB proteins or classes of proteins and by genome-wide discovery
      approaches. Antigens and epitopes recognized by classically restricted CD4(+) and
      CD8(+) T cells show extensive breadth and diversity in MTB-infected humans. 

PMID- 24852056
TI  - Polysubstance use: diagnostic challenges, patterns of use and health.
AB  - PURPOSE OF REVIEW: Polysubstance use is common, particularly amongst some age
      groups and subcultures. It is also associated with elevated risk of psychiatric
      and physical health problems. We review the recent research findings, comment on
      changes to polysubstance diagnoses, report on contemporary clinical and
      epidemiological polysubstance trends, and examine the efficacy of preventive and
      treatment approaches. RECENT FINDINGS: Approaches to describing polysubstance use
      profiles are becoming more sophisticated. Models over the last 18 months that
      employ latent class analysis typically report a no use or limited-range cluster
      (alcohol, tobacco and marijuana), a moderate-range cluster (limited range and
      amphetamine derivatives), and an extended-range cluster (moderate range, and
      nonmedical use of prescription drugs and other illicit drugs). Prevalence rates
      vary as a function of the population surveyed. Wide-ranging polysubstance users
      carry higher risk of comorbid psychopathology, health problems, and deficits in
      cognitive functioning. SUMMARY: Wide-ranging polysubstance use is more prevalent
      in subcultures such as 'ravers' (dance club attendees) and those already
      dependent on substances. Health risks are elevated in these groups. Research into
      the prevention and treatment of polysubstance use is underdeveloped. There may be
      benefit in targeting specific polysubstance use and risk profiles in prevention
      and clinical research.

PMID- 24852057
TI  - Diagnosis telling in people with psychosis.
AB  - PURPOSE OF REVIEW: There are complexities in communicating diagnostic information
      relating to schizophrenia spectrum disorders. There is a current dearth of
      research in understanding how clinicians effectively communicate with service
      users about such diagnostic news. In this review, we aim to synthesize the latest
      research throughout 2012 and 2013 that presented data relating to the
      communication of a diagnosis of schizophrenia spectrum disorders, including
      individuals who had experienced first-episode psychosis or were in at-risk mental
      states. Comprehensive database and manual searches were conducted which obtained
      data from both service users and health professional groups. RECENT FINDINGS:
      Fourteen quantitative and qualitative studies were found. The majority of studies
      were descriptive and heterogeneous in content. Key themes included service user
      preferences towards disclosure and diagnostic terminology, health professional
      training, stigma-related issues and the use of diagnostic communication models.
      SUMMARY: Overall, communication models that foster therapeutic relationships and
      actively encourage the health professional to reduce stigma may be a key to
      initial diagnostic discussions in clinical practice. Such communication models
      and intervention require further more rigorous evaluation, as none have been
      tested through randomized controlled protocols in clinical settings.

PMID- 24852058
TI  - Peer support in mental health services.
AB  - PURPOSE OF REVIEW: Considering international diversity in the implementation of
      mental health peer support and an increasing research interest in peer support
      work (PSW), this review focuses on priorities in current research and practice.
      With grassroots in informal services for people with mental health problems, peer
      support has been strengthened by the recovery paradigm in mental health policy,
      and there are steps towards integration in statutory services. RECENT FINDINGS:
      Current issues include benefits of peer support, its efficacy and effectiveness.
      The value of peer support in formal and informal settings is discussed, and
      organizational change processes and the challenges in peer support implementation
      are discussed. Recent studies have identified the need for a clarification of
      roles, competencies and job structure and for adequate training and supervision.
      Along with reported benefits for consumer and PSW involvement in care revealed by
      mixed method studies, destigmatization at the personal and system level is a
      crucial PSW component. SUMMARY: Various types of peer support merit further
      evaluation. Assessing the impact of peer support on service users, peer providers
      and organizations require complex intervention studies, using mixed methods
      designs with qualitative exploration of underlying processes and experiences to
      complement high-quality controlled trials.

PMID- 24852059
TI  - Review of the energy drink literature from 2013: findings continue to support
      most risk from mixing with alcohol.
AB  - PURPOSE OF REVIEW: In the field of caffeine research, interest in and concern for
      energy drink consumption have grown. Most caffeine-related research studies
      published in 2013 focused on energy drink consumption. This article reviews this
      literature. RECENT FINDINGS: Prevalence of energy drink consumption varies by
      measure and age group. Lack of a standardized definition of use inhibits
      comparison across studies. Studies reviewed show that energy drink consumption is
      generally low, but the minority who drink the most may be consuming at unsafe
      levels. Energy drinks are popular among adolescents and young adults. They boost
      energy and alertness in some conditions, but may have adverse hemodynamic
      effects. Harmful consequences, including involvement in risky driving, riding
      with an intoxicated driver and being taken advantage of sexually, were reported
      significantly more often by adolescents and young adults who combined energy
      drinks with alcohol compared with those who did not. SUMMARY: This review of
      recent literature focused on prevalence, motivation, and consequences of energy
      drink use. Clear findings emerged only on the dangers of mixing alcohol and
      energy drinks. The lack of a standardized measure made the comparison across
      studies difficult. Future research should extend and clarify these findings using
      standardized measures of use.

PMID- 24852060
TI  - Prevention of common mental disorders: conceptual framework and effective
      interventions.
AB  - PURPOSE OF REVIEW: Mental disorders take a major toll, economically, socially,
      and psychologically, on individuals, families, and societies. Prevention provides
      an important and realistic opportunity to overcome this major health problem.
      This review outlines a conceptual framework for mental health prevention and
      effective strategies and programs for the prevention of mental disorders. RECENT
      FINDINGS: Risk and protective factors for mental illness provide leverage points
      for prevention interventions. A life course perspective, looking at disease from
      conception, pregnancy, parenting, infancy, childhood, adolescence, adulthood to
      aging, emphasizes the importance of targeting prevention efforts as early as
      possible in life. Currently available effective and realistic preventions
      targeting major phases of life including both universal (community) and selective
      high-risk approaches are noted. The Internet and its associated technologies are
      seen to have great potential for prevention. SUMMARY: Common mental disorders are
      preventable, and prevention is cost-effective. Although the evidence base for the
      prevention of mental disorders needs to be expanded with rigorous large-scale
      pragmatic trials of promising effective programs, we have at our disposal strong
      evidence and effective tools on which to base prevention efforts. These facts
      need to be fully communicated to providers, policy makers, and the population at
      large, and acted upon.

PMID- 24852061
TI  - Insights on the evolution of plant succulence from a remarkable radiation in
      Madagascar (Euphorbia).
AB  - Patterns of adaptation in response to environmental variation are central to our
      understanding of biodiversity, but predictions of how and when broad-scale
      environmental conditions such as climate affect organismal form and function
      remain incomplete. Succulent plants have evolved in response to arid conditions
      repeatedly, with various plant organs such as leaves, stems, and roots physically
      modified to increase water storage. Here, we investigate the role played by
      climate conditions in shaping the evolution of succulent forms in a plant clade
      endemic to Madagascar and the surrounding islands, part of the hyper-diverse
      genus Euphorbia (Euphorbiaceae). We used multivariate ordination of 19 climate
      variables to identify links between particular climate variables and three major
      forms of succulence-succulent leaves, cactiform stem succulence, and tubers. We
      then tested the relationship between climatic conditions and succulence, using
      comparative methods that account for shared evolutionary history. We confirm that
      plant water storage is associated with the two components of aridity,
      temperature, and precipitation. Cactiform stem succulence, however, is not
      prevalent in the driest environments, countering the widely held view of
      cactiforms as desert icons. Instead, leaf succulence and tubers are significantly
      associated with the lowest levels of precipitation. Our findings provide a clear
      link between broad-scale climatic conditions and adaptation in land plants, and
      new insights into the climatic conditions favoring different forms of succulence.
      This evidence for adaptation to climate raises concern over the evolutionary
      future of succulent plants as they, along with other organisms, face
      anthropogenic climate change.

PMID- 24852062
TI  - Waiting list scandal prompts calls for shake-up at US Veterans Affairs.

PMID- 24852063
TI  - Framing comorbidities and co-occurrences in a migraine with aura patient.

PMID- 24852064
TI  - An alarming deterioration of neurological status.

PMID- 24852065
TI  - Histology of the suprapubic and anogenital cutaneous glands in male cotton top
      tamarins (Saguinus oedipus).
AB  - In cotton top tamarins (Saguinus oedipus), scent glands have been mostly studied
      in females from museum collections. This work aims to extend the investigation to
      male specimens, introducing a novel source of skin samples. Two adult males from
      zoo populations, one intact and one castrated, were immediately frozen after
      natural death. Skin samples were later collected at the thawing onset, soaked
      with cold fixative and processed for light microscopy. Sebaceous units of scent
      glands showed phasic secretory activity in the intact male and marked fibrosis in
      the castrated male. It appears, therefore, that light microscopy samples from
      frozen tissues provide detailed features that can disclose distinctive traits in
      specimens characterized by different hormonal balances.

PMID- 24852067
TI  - Evaluating the patients with thalassemia major for long-term endocrinological
      complications after bone marrow transplantation.
AB  - The aim of this study was to evaluate the endocrinological complications of the
      patients with thalassemia major (TM) who underwent bone marrow transplantation
      (BMT) and followed-up more than two years in our center, prospectively. "BMT
      group" consisted of 41 patients with TM. The mean age was 12.4 +/- 5.4 years and
      transplantation age was mean 7.5 +/- 4.9 years. Post-BMT follow-up lasted from 24
      to 122 months (mean 65.07 months). Also, 32 TM patients with similar age group
      and same history of transfusion and chelation therapy were recruited for the
      study as "control (C) group". The weight SDS score after transplantation was
      found better than before transplantation (p = 0.010). There was a negative
      correlation between height SDS and BMT age (p = 0.008). The height SDS scores
      were better in patients whose BMT age was under seven years old compared to those
      older than seven years old (p = 0.02). Z-scores of femur neck and L2-4 vertebrae
      DEXA were decreased (p = 0.032, p = 0.0001) and incidence of insulin resistance
      increased (p = 0.01) in patients with increased BMT age. The risk of gonadal
      insufficiency was significantly lower in the patients who underwent BMT <7 years
      of age (p = 0.009). There was no statistically significant relationship between
      BMT age and complications such as hypothyroidism, hypoparathyroidism, and adrenal
      insufficiency. The patients with TM should be evaluated for transplantation in
      early stage of the disease, especially before the age of seven years. Because the
      BMT cannot correct the endocrinological complications of TM completely, the
      patients should be followed up regularly after the transplantation. 

PMID- 24852068
TI  - Prescription and repair rates of prosthetic limbs in the VA healthcare system:
      implications for national prosthetic parity.
AB  - Abstract Purpose: To quantify prescription and repair rates of prosthetic limbs
      in the Department of Veterans Affairs (VA) and explore differences by level,
      type, and age. Methods: Veterans (N = 32 440) with an initial prosthetic
      prescription between 2000 and 2010 were classified by amputation level and type.
      Annual rates of prescription and repair were calculated using person-time and
      compared by group. Results: Veterans with upper limb amputation had lower annual
      prescription and repair rates (0.28 and 0.21) compared with those with lower limb
      amputation (0.40 and 0.56). Myoelectric devices users had higher prescription
      rates. However, body-powered users had higher repair rates. Prescription and
      repair rates for microprocessor knee joints were higher than for fluid and
      friction devices. Veterans under 65 had 0.07 and 0.16 higher rates of
      prescription and repair than those over 65 (p < 0.0001). Conclusions: Because the
      VA is unconstrained by co-pays or caps, data on prosthetic prescription and
      repair can be used to estimate rates that might occur if national prosthetic
      parity laws were adopted. Given the rates found, it is likely that annual costs
      would exceed the typical annual and/or lifetime caps in most insurance plans. In
      states without prosthetic parity laws, such costs likely limit access to needed
      devices. Implications for Rehabilitation For the almost 2 million people in the
      United States living with an amputation or congenital limb loss, purchasing and
      maintaining a prosthetic limb can be costly, with insurances often imposing
      annual or lifetime caps. Data on prosthetic purchasing and repair is limited and
      reliant on self-reported information. Because the VA is unconstrained by co-pays
      or caps, claims data on prosthetic prescription and repair can be used to
      estimate rates that might occur if national prosthetic parity laws were adopted.
      Given the rates found, it is likely that annual costs would exceed the typical
      annual and/or lifetime caps in most insurance plans. In states without prosthetic
      parity laws, such costs likely limit access to needed devices.

PMID- 24852066
TI  - Specific analogues uncouple transport, signalling, oligo-ubiquitination and
      endocytosis in the yeast Gap1 amino acid transceptor.
AB  - The Saccharomyces cerevisiae amino acid transceptor Gap1 functions as receptor
      for signalling to the PKA pathway and concomitantly undergoes substrate-induced
      oligo-ubiquitination and endocytosis. We have identified specific amino acids and
      analogues that uncouple to certain extent signalling, transport, oligo
      ubiquitination and endocytosis. L-lysine, L-histidine and L-tryptophan are
      transported by Gap1 but do not trigger signalling. Unlike L-histidine, L-lysine
      triggers Gap1 oligo-ubiquitination without substantial induction of endocytosis.
      Two transported, non-metabolizable signalling agonists, beta-alanine and D
      histidine, are strong and weak inducers of Gap1 endocytosis, respectively, but
      both causing Gap1 oligo-ubiquitination. The non-signalling agonist, non
      transported competitive inhibitor of Gap1 transport, L-Asp-gamma-L-Phe, induces
      oligo-ubiquitination but no discernible endocytosis. The Km of L-citrulline
      transport is much lower than the threshold concentration for signalling and
      endocytosis. These results show that molecules can be transported without
      triggering signalling or substantial endocytosis, and that oligo-ubiquitination
      and endocytosis do not require signalling nor metabolism. Oligo-ubiquitination is
      required, but apparently not sufficient to trigger endocytosis. In addition, we
      demonstrate intracellular cross-induction of endocytosis of transport-defective
      Gap1(Y395C) by ubiquitination- and endocytosis-deficient Gap1(K9R,K16R). Our
      results support the concept that different substrates bind to partially
      overlapping binding sites in the same general substrate-binding pocket of Gap1,
      triggering divergent conformations, resulting in different conformation-induced
      downstream processes.

PMID- 24852069
TI  - Anti-VEGF therapy in myopic choroidal neovascularization: long-term results.
AB  - PURPOSE: To evaluate the medium- and long-term efficacy of anti-VEGF agents in
      the treatment of choroidal neovascularization secondary to pathologic myopia
      (mCNV). METHODS: We performed a retrospective analysis of patients with mCNV who
      had been treated with intravitreous anti-VEGF for at least 2 years. The best
      corrected visual acuity (BCVA) and central retinal thickness (CRT) were compared
      before and after the treatment. The number of injections per year was also
      assessed. RESULTS: The results were analysed at 2 years for 67 eyes, at 3 years
      for 52 eyes, at 4 years for 28 eyes and at 5 years for 13 eyes. The mean change
      from baseline BCVA was significant at 2 years (+8.6 letters; p < 0.001) and this
      gain remained significantly stable for a period of 5 years. The mean CRT showed a
      significant decrease over time, with a nadir at 2 years (-104.0 MUm; p < 0.001).
      The mean number of injections performed during the first year was 5.2, being
      lower in subsequent years (p < 0.001). CONCLUSION: In this subset of patients
      with mCNV, an intravitreous therapy with anti-VEGF agents proved to have
      effective results over 5 years, with a sustained increase in BCVA.

PMID- 24852070
TI  - Reaction mechanism and product branching ratios of the CH + C3H8 reaction: a
      theoretical study.
AB  - The C4H9 potential energy surface accessed by the reaction of methylidyne
      radical, CH (X(2)Pi), with propane, C3H8, including possible intermediates,
      transition states and dissociation products, has been studied by ab initio and
      density functional calculations at the CCSD(T)/CBS//B3LYP/6-311G(d,p) level of
      theory. The computed relative energies and molecular parameters were utilized to
      calculate collision-energy-dependent unimolecular rate constants at the zero
      pressure limit for isomerization and dissociation channels of the C4H9 adducts
      formed in the entrance reaction channels. The rate constants were used to
      evaluate the product branching ratios in the CH + C3H8 reaction under single
      collision conditions. The results show that the reaction can produce mostly
      ethene (C2H4) + ethyl radical (C2H5) and propene (C3H6) + methyl radical (CH3),
      and up to 14% of various butene isomers (C4H8) + H. The product branching ratios
      are sensitive to the initial reaction adduct (a butyl radical, C4H9) formed in
      the entrance channels via barrierless insertion of the CH radical into the
      terminal and middle C-H bonds of propane or, possibly, into the single C-C bonds.
      A more definite answer on relative contributions of various available CH
      insertion channels can be obtained through ab initio quasiclassical trajectory
      calculations, which are proposed for the future. The results allowed us to
      conclude that the CH + C3H8 reaction does not result in major amounts in the
      direct growth of the carbon-skeleton to four-carbon C4H8 products via the CH-for
      H exchange because C-C bond cleavages in C4H9 radicals are generally more
      preferable than C-H bond cleavages. 

PMID- 24852071
TI  - Early myocardial deformation abnormalities in breast cancer survivors.
AB  - To evaluate the role of 2D myocardial strain (rate) imaging in the detection of
      early subclinical cardiotoxicity in breast cancer survivors treated with an
      anthracycline-based chemotherapeutic regimen. 57 adult breast cancer survivors
      were analyzed 1 year after therapy. All patients underwent biomarker analysis and
      2D echocardiography consisting of conventional echocardiographic and strain
      (rate) parameters. Conventional echocardiographic values were normal. Global
      longitudinal strain was normal, but 18 % of patients showed a >2 SD decrease when
      individually compared to reference values. This subgroup showed a decrease in end
      systolic and end-diastolic volumes and an increase in left ventricular mass.
      Radial and circumferential strain rates were significantly decreased in the whole
      study group. 2D myocardial strain (rate) imaging showed abnormalities in breast
      cancer survivors, while conventional echocardiographic values remained normal,
      rendering 2D myocardial strain (rate) imaging an interesting tool for the early
      detection of anthracycline-induced cardiotoxicity. 

PMID- 24852072
TI  - Complete genome sequence analysis of an enterovirus 75 isolate from China.
AB  - Enterovirus 75 (EV-B75) is a member of the species Enterovirus B (EV-B). So far,
      only the complete genome of the prototype strain from the United States is
      available. Here, we report the genome sequence of an EV-B75 isolate from an acute
      flaccid paralysis patient in China. Sequence analysis revealed high nucleotide
      sequence divergence from foreign EV-B75 strains and suggested several
      recombination events with other serotypes of EV-B.

PMID- 24852073
TI  - Characterization of epizootic hemorrhagic disease virus from a bovine with
      clinical disease with high nucleotide sequence identity to white-tailed deer
      isolates.
AB  - Epizootic hemorrhagic disease virus (EHDV) was isolated from a pregnant cow in
      Indiana, USA, exhibiting excessive salivation, pyrexia and abortion. VP2, VP5,
      and VP7 sequences of the isolated bovine EHDV showed 97.7, 97.4, and 97.9 %
      identity to a serotype 2 reference virus. Bovine EHDV was closely related (>99.9
      %) to white tailed deer (WTD) EHDV collected from Iowa in 2013 and showed less
      than 2.1 % divergence from EHDV collected from WTD across the USA in 2013. The
      high degree of sequence identity between bovine and WTD EHDV isolates
      demonstrates that similar viruses concurrently circulate in both species and
      suggests possible further incursions into bovines.

PMID- 24852076
TI  - Decreased cyclooxygenase-2 gene expression and lactoferrin release in blood
      neutrophils of heifers during the calving period.
AB  - Immunosuppression during the calving period in dairy cows is associated with an
      increased risk of diseases. Correct neutrophil function is a key mechanism of
      innate immunity that is used to protect the host from pathogenic microorganisms.
      The aim of this study was to evaluate the function of blood neutrophils obtained
      from heifers between 30 days preparturition and 30 days postparturition. We
      assessed the phagocytosis of fluorescent bioparticles using flow cytometry,
      chemotaxis induced by chemoattractants using the transwell plate assay,
      lactoferrin release using ELISA and cyclooxygenase-2 (COX-2) gene expression
      using real time-PCR. Our results showed an increased ability of phagocytosis of
      bioparticles and chemotaxis induced by the chemotactic agent platelet activating
      factor (PAF), between day 15 preparturition until day 30 postparturition, and at
      calving, respectively. COX-2 gene expression induced by PAF was increased only in
      neutrophils obtained at days 30 pre- and post-parturition (p<0.001). Neutrophil
      lactoferrin release was reduced between day 15 preparturition and day 30
      postparturition compared with that at day 30 preparturition. Furthermore,
      lactoferrin plasma levels were increased at calving. In conclusion, we provided
      evidence that neutrophils from heifers around calving time exhibit impairment of
      particular defensive functions, such as COX-2 mRNA expression and lactoferrin,
      suggesting that these mechanisms may contribute to immunosuppression in cows
      around calving.

PMID- 24852075
TI  - Comparison of gene expression of immune mediators in lung and pulmonary lymph
      node granulomas from cattle experimentally infected with Mycobacterium bovis.
AB  - The cellular infiltrates and macrophage activation pathways may differ in
      granulomas found in the lungs and pulmonary lymph nodes of cattle infected with
      Mycobacterium bovis. The aim of this study was to compare the histopathology and
      gene expression profiles of cytokines and immune mediators for cattle which had
      these lesions in both sites. Ten Friesian-cross, 15-16 month old cattle were
      challenged intratracheally with 5 * 10(3)CFU of virulent M. bovis and killed and
      necropsied at 28 weeks after infection. Seven animals were found to have gross TB
      granulomas in both their lungs and pulmonary lymph nodes (PLN) and these lesions
      were fully encapsulated with central necrosis and mineralisation. Neutrophil
      infiltration was clearly involved in granuloma in lung whereas neutrophils were
      limited in lesions of PLN. Comparisons were made of immune mediators from these
      two sites from the same animals as well as those between lesioned PLN tissues and
      non-lesioned prescapular lymph nodes (PSLN). Gene expressions of the immune
      mediators were normalised using a housekeeping gene (U1), a monocyte/macrophage
      marker (CD14) and a common leucocyte marker (CD45). mRNA expression of IFN-gamma,
      IL-17A, IRF5(1) and arginase 1 (Arg1) was significantly up-regulated in lung
      compared to that for PLN (p<0.05), while mRNA expression of IFN-gamma, IL-12p40,
      TNF-alpha and iNOs for PLN was significantly higher than that for PSLN (p<0.05).
      In addition, IL-10 mRNA expression was significantly higher for lung compared to
      PLN when normalised for CD45 (p<0.05). The results suggested that the stronger
      proinflammatory immune response in the lesioned lung may be a consequence of
      enhanced expression of IRF5 promoting IFN-gamma and IL-17 production. In
      contrast, Arg1 expression in the lungs could facilitate the infection through
      competing with iNOs for l-arginine, preventing generation of nitric oxide for
      clearance of M. bovis infection.

PMID- 24852074
TI  - Repeat associated non-ATG (RAN) translation: new starts in microsatellite
      expansion disorders.
AB  - Microsatellite-expansion diseases are a class of neurological and neuromuscular
      disorders caused by the expansion of short stretches of repetitive DNA (e.g.
      GGGGCC, CAG, CTG ...) within the human genome. Since their discovery 20 years
      ago, research into how microsatellites expansions cause disease has been examined
      using the model that these genes are expressed in one direction and that
      expansion mutations only encode proteins when located in an ATG-initiated open
      reading frame. The fact that these mutations are often bidirectionally
      transcribed combined with the recent discovery of repeat associated non-ATG (RAN)
      translation provides new perspectives on how these expansion mutations are
      expressed and impact disease. Two expansion transcripts and a set of unexpected
      RAN proteins must now be considered for both coding and 'non-coding' expansion
      disorders. RAN proteins have been reported in a growing number of diseases,
      including spinocerebellar ataxia type 8 (SCA8), myotonic dystrophy type 1 (DM1),
      Fragile-X tremor ataxia syndrome (FXTAS), and C9ORF72 amyotrophic lateral
      sclerosis (ALS)/frontotemporal dementia (FTD). 

PMID- 24852078
TI  - Critical slowing down and noise-induced intermittency in bistable perception:
      bifurcation analysis.
AB  - Stochastic dynamics and critical slowing down were studied experimentally and
      numerically near the onset of dynamical bistability in visual perception under
      the influence of noise. Exploring the Necker cube as the essential example of an
      ambiguous figure, and using its wire contrast as a control parameter, we measured
      dynamical hysteresis in two coexisting percepts as a function of both the
      velocity of the parameter change and the background luminance. The bifurcation
      analysis allowed us to estimate the level of cognitive noise inherent to brain
      neural cells activity, which induced intermittent switches between different
      perception states. The results of numerical simulations with a simple energy
      model are in good qualitative agreement with psychological experiments. 

PMID- 24852077
TI  - Optimisation of antiretroviral therapy in HIV-infected children under 3 years of
      age.
AB  - BACKGROUND: In the absence of antiretroviral therapy (ART), over 50% of HIV
      infected infants progress to AIDS and death by 2 years of age. However, there are
      challenges to initiation of ART in early life, including the possibility of drug
      resistance in the context of prevention of mother-to-child transmission (PMTCT)
      programs, a paucity of drug choices , uncertain dosing for some medications and
      long-term toxicities. Key management decisions include when to start ART, what
      regimen to start, and whether and when to substitute drugs or interrupt therapy.
      This review, an update of a previous review, aims to summarize the currently
      available evidence on this topic and inform the ART management in HIV-infected
      children less than 3 years of age. OBJECTIVES: To evaluate 1) when to start ART
      in young children (less than 3 years); 2) what ART to start with, comparing first
      line non-nucleoside reverse transcriptase inhibitor (NNRTI) and protease
      inhibitor (PI)-based regimens; and 3) whether alternative strategies should be
      used to optimize antiretroviral treatment in this population: induction
      (initiation with 4 drugs rather than 3 drugs) followed by maintenance ART,
      interruption of ART and substitution of PI with NNRTI drugs once virological
      suppression is achieved on a PI-based regimen. SEARCH METHODS: Search methodsWe
      searched for published studies in the Cochrane HIV/AIDS Review Group Trials
      Register, The Cochrane Library, Pubmed, EMBASE and CENTRAL. We screened abstracts
      from relevant conference proceedings and searched for unpublished and ongoing
      trials in clinical trial registries (ClinicalTrials.gov and the WHO International
      Clinical Trials Registry Platform). SELECTION CRITERIA: We identified RCTs that
      recruited perinatally HIV-infected children under 3 years of age without
      restriction of setting. We rejected trials that did not include children less
      than 3 years of age, did not provide stratified outcomes for those less than 3
      years or did not evaluate either timing of ART initiation, choice of drug regimen
      or treatment switch/interruption strategy. DATA COLLECTION AND ANALYSIS: Two
      reviewers independently applied study selection criteria, assessed study quality
      and extracted data. Effects were assessed using the hazard ratio (HR) for time-to
      event outcomes, relative risk for dichotomous outcomes and weighted mean
      difference for continuous outcomes. MAIN RESULTS: A search of the databases
      identified a total of 735 unique, previously unreviewed studies, of which 731
      were excluded to leave 4 new studies to incorporate into the review. Four
      additional studies were identified in conference proceedings, for a total of 8
      studies addressing when to start treatment (n=2), what to start (n=3), whether to
      substitute lopinavir/ritonavir (LPV/r) with nevirapine (NVP) (n=1), whether to
      use an induction-maintenance ART strategy (n=1) and whether to interrupt
      treatment (n=1).Treatment initiation in asymptomatic infants with good
      immunological status was associated with a 75% reduction (HR=0.25; 95%CI 0.12
      0.51; p=0.0002) in mortality or disease progression in the one trial with
      sufficient power to address this question. In a smaller pilot trial, median CD4
      cell count was not significantly different between early and deferred treatment
      groups 12 months after ART.Regardless of previous exposure to nevirapine for
      PMTCT, the hazard for treatment failure at 24 weeks was 1.79 (95%CI 1.33, 2.41)
      times higher in children starting ART with a NVP-based regimen compared to those
      starting with a LPV/r-based regimen (p=0.0001) with no clear difference in the
      effect observed for children younger or older than 1 year. The hazard for
      virological failure at 24 weeks was overall 1.84 (95%CI 1.29, 2.63) times higher
      for children starting ART with a NVP-based regimen compared to those starting
      with a LPV/r-based regimen (p=0.0008) with a larger difference in time to
      virological failure (or death) between the NVP and LPV/r-based regimens when ART
      was initiated in the first year of life.Infants starting a LPV/r regimen and
      achieving sustained virological suppression who then substituted LPV/r with NVP
      after median 9 months on LPV/r were less likely to develop virological failure
      (defined as at least one VL greater than 50 copies/mL) compared with infants who
      started and stayed on LPV/r (HR=0.62, 95%CI 0.41, 0.92, p=0.02). However the
      hazard for confirmed failure at a higher viral load (>1000 copies/mL) was greater
      among children who switched to NVP compared to those who remained on LPV/r
      (HR=10.19, 95% CI 2.36, 43.94, p=0.002).Children undergoing an induction
      maintenance ART approach with a 4-drug NNRTI-based regimen for 36 weeks, followed
      by 3-drug ART, had significantly greater CD4 rise than children receiving a
      standard 3-drug NNRTI-based ART at 36 weeks (mean difference 1.70 [95%CI 0.61,
      2.79] p=0.002) and significantly better viral load response at 24 weeks (OR 1.99
      [95%CI 1.09, 3.62] p=0.02). However, the immunological and virological benefits
      were short-term.The one trial of treatment interruption that compared children
      initiating continuous ART from infancy with children interrupting ART was
      terminated early because the duration of treatment interruption was less than 3
      months in most infants. Children interrupting treatment had similar growth and
      occurrence of serious adverse events as those in the continuous arm. AUTHORS'
      CONCLUSIONS: ART initiation in asymptomatic children under 1 year of age reduces
      morbidity and mortality, but it remains unclear whether there are clinical
      benefits to starting ART in asymptomatic children diagnosed with HIV infection
      between 1-3 years.The available evidence shows that a LPV/r-based first-line
      regimen is more efficacious than a NVP-based regimen, regardless of PMTCT
      exposure status. New formulations of LPV/r are urgently required to enable new
      WHO recommendations to be implemented. An alternative approach to long-term LPV/r
      is substituting LPV/r with NVP once virological suppression is achieved. This
      strategy looked promising in the one trial undertaken, but may be difficult to
      implement in the absence of routine viral load testing.A 4-drug induction
      maintenance approach showed short-term virological and immunological benefits
      during the induction phase but, in the absence of sustained benefits, is not
      recommended as a routine treatment strategy. Treatment interruption following
      early ART initiation in infancy was challenging for children who were severely
      immunocompromised in the context of poor clinical immunological condition at ART
      initiation due to the short duration of interruption, and is therefore not
      practical in ART treatment programmes where close monitoring is not feasible.

PMID- 24852079
TI  - Enhanced piezoelectric and mechanical properties of AlN-modified BaTiO3 composite
      ceramics.
AB  - BaTiO3-xAlN (BT-xAlN) composite ceramics were prepared by conventional solid
      state reaction sintering. The effects of the AlN content on the crystalline
      structures, densities, and electrical and mechanical properties of the BT
      ceramics were investigated. The BT-1.5%AlN ceramic exhibits a good piezoelectric
      constant of 305 pC N(-1) and an improved Vickers hardness of 5.9 GPa. The
      enhanced piezoelectricity originates from interactions between defect dipoles and
      spontaneous polarization inside the domains due to the occurrence of local
      symmetry, caused by the preferential distribution of the Al(3+)-N(3-) pairs
      vertical to the c axis. The hardening of the material is attributed to the
      improved density, and particle and grain boundary strengthening. Our work
      indicates that if a suitable doping ion pair is designed, lead-free ceramic
      systems prepared from ordinary raw materials by a conventional sintering method
      have a high probability of exhibiting good piezoelectric and mechanical
      properties simultaneously. 

PMID- 24852080
TI  - Highly efficient one-pot labeling of new phosphonium cations with fluorine-18 as
      potential PET agents for myocardial perfusion imaging.
AB  - Lipophilic cations such as phosphonium salts can accumulate in mitochondria of
      heart in response to the negative inner-transmembrane potentials. Two phosphonium
      salts [(18)F]FMBTP and [(18)F]mFMBTP were prepared and evaluated as potential
      myocardial perfusion imaging (MPI) agents in this study. The cations were
      radiolabeled via a simplified one-pot method starting from [(18)F]fluoride and
      followed by physicochemical property tests, in vitro cellular uptake assay, ex
      vivo mouse biodistribution, and in vivo rat microPET imaging. The total
      radiosynthesis time was less than 60 min including HPLC purification. The [(18)F]
      labeled compounds were obtained in high radiolabeling yield (~50%) and good
      radiochemical purity (>99%). Both compounds were electropositive, and their log P
      values at pH 7.4 were 1.16 +/- 0.003 (n = 3) and 1.05 +/- 0.01 (n = 3),
      respectively. Both [(18)F]FMBTP and [(18)F]mFMBTP had high heart uptake (25.24 +/
      2.97% ID/g and 31.02 +/- 0.33% ID/g at 5 min postinjection (p.i.)) in mice with
      good retention (28.99 +/- 3.54% ID/g and 26.82 +/- 3.46% ID/g at 120 min p.i.).
      From the PET images in rats, the cations exhibited high myocardium uptake and
      fast clearance from liver and small intestine to give high-contrast images across
      all time points. These phosphonium cations were radiosynthesized via a highly
      efficient one-pot procedure for potential MPI offering high heart accumulation
      and rapid nontarget clearance. 

PMID- 24852081
TI  - Open and laparoscopic resection of hepatocellular adenoma: trends over 23 years
      at a specialist hepatobiliary unit.
AB  - BACKGROUND: Hepatocellular adenoma (HCA) is a rare benign liver epithelial tumour
      that can require surgery. This retrospective study reports a 23-year experience
      of open and laparoscopic resections for HCA. METHODS: Patients with a
      histological diagnosis of HCA were included in this analysis. Surgical resection
      was performed in all symptomatic patients and in those with lesions measuring >5
      cm. RESULTS: Between 1989 and 2012, 62 patients, 59 of whom were female,
      underwent surgery for HCA (26 by open surgery and 36 by laparoscopic surgery).
      Overall, 96.6% of female patients had a history of contraceptive use; 54.8% of
      patients presented with abdominal pain and 11.2% with haemorrhage; the remaining
      patients were asymptomatic. Patients who underwent laparoscopy had smaller
      lesions (mean +/- standard deviation diameter: 68.3 +/- 35.2 mm versus 91.9 +/-
      42.5 mm; P = 0.022). Operatively, laparoscopic and open liver resection did not
      differ except in the number of pedicle clamps, which was significantly lower in
      the laparoscopic group (27.8% versus 57.7% of patients; P = 0.008). Postoperative
      variables did not differ between the groups. Mortality was nil. Two surgical
      specimens were classified as HCA/borderline hepatocellular carcinoma. At the 3
      year follow-up, all patients were alive with no recurrence of HCA. CONCLUSIONS:
      Open and laparoscopic liver resections are both safe and feasible approaches for
      the surgical management of HCA. However, laparoscopic liver resections may be
      limited by lesion size and location and require advanced surgical skills.

PMID- 24852082
TI  - Jadeite in Chelyabinsk meteorite and the nature of an impact event on its parent
      body.
AB  - The Chelyabinsk asteroid impact is the second largest asteroid airburst in our
      recorded history. To prepare for a potential threat from asteroid impacts, it is
      important to understand the nature and formational history of Near-Earth Objects
      (NEOs) like Chelyabinsk asteroid. In orbital evolution of an asteroid, collision
      with other asteroids is a key process. Here, we show the existence of a high
      pressure mineral jadeite in shock-melt veins of Chelyabinsk meteorite. Based on
      the mineral assemblage and calculated solidification time of the shock-melt
      veins, the equilibrium shock pressure and its duration were estimated to be at
      least 3-12 GPa and longer than 70 ms, respectively. This suggests that an
      impactor larger than 0.15-0.19 km in diameter collided with the Chelyabinsk
      parent body at a speed of at least 0.4-1.5 km/s. This impact might have separated
      the Chelyabinsk asteroid from its parent body and delivered it to the Earth. 

PMID- 24852085
TI  - Non-English speaking is a predictor of survival after admission to intensive
      care.
AB  - PURPOSE: The relationship between English proficiency and health care outcomes in
      intensive care has rarely been examined. This study aimed to determine whether
      being a non-English speaker would predict mortality in a critical care setting.
      Secondary end points were intensive care unit (ICU) and hospital length of stay.
      MATERIALS AND METHODS: This is a single-center, retrospective, cohort study of
      admissions from January 1, 2000 until December 31, 2011 in a tertiary level
      intensive care setting in Melbourne, Australia. All admissions during the study
      period were included. Patients without language data were excluded. Of those with
      multiple admissions, only the first was included. Analysis of 20082 ICU
      admissions was undertaken, of which 19059 (94.9%) were English speakers. RESULTS:
      After adjusting for confounding variables (age, severity of illness, diagnostic
      group, year of admission, and socioeconomic status), English-speaking status was
      independently associated with an increased risk of death (odds ratio, 1.91; 95%
      confidence interval 1.46-2.49; P < .001). There was no difference in ICU length
      of stay between groups. Hospital length of stay was shorter for English speakers.
      CONCLUSION: Contrary to expectations, this large single-center study shows a
      consistent relationship between non-English-speaking status and increased
      survival after admission to ICU.

PMID- 24852086
TI  - Reply to Letter to Editor: "Kriek R., Marketing messages in pharmacological
      papers and scientific chapters: The case of palmitoylethanolamide and its
      formulations" [Pharmacol Res (2014) 10.1016/j.phrs.2014.04.007].

PMID- 24852084
TI  - Plasmid profile and pulsed-field gel electrophoresis analysis of Salmonella
      enterica isolates from humans in Turkey.
AB  - This study was conducted for typing Salmonella enterica subspecies enterica
      strains in Turkey using pulsed-field gel electrophoresis (PFGE) and plasmid DNA
      profile analysis. Fourty-two strains were isolated from clinical samples obtained
      from unrelated patients with acute diarrhea. The samples were collected from
      state hospitals and public health laboratories located at seven provinces in
      different regions of Turkey at different times between 2004 and 2010. The strains
      were determined to belong to 4 different serovars. The Salmonella enterica
      strains belonged to the serovars Salmonella Enteritidis (n = 23), Salmonella
      Infantis (n = 14), Salmonella Munchen (n = 2), and Salmonella Typhi (n = 3).
      Forty-two Salmonella enterica strains were typed with PFGE methods using XbaI
      restriction enzyme and plasmid analysis. At the end of typing, 11 different PFGE
      band profiles were obtained. Four different PFGE profiles (type 1, 4, 9, and 10)
      were found among serotype S. Enteritidis species, 3 different PFGE profiles (type
      3, 5, 6) were found among S. Infantis species, 2 different PFGE profiles were
      found among S. Typhi species (type 2 and 11), and 2 different PFGE profiles were
      found among S. Munchen species (type 7, 8). The UPGMA dendrogram was built on the
      PFGE profiles. In this study, it was determined that 4 strains of 42 Salmonella
      enterica strains possess no plasmid, while the isolates have 1-3 plasmids ranging
      from 5.0 to 150 kb and making 12 different plasmid profiles (P1-P12). In this
      study, we have applied the analysis of the PFGE patterns and used bioinformatics
      methods to identify both inter and intra serotype relationships of 4 frequently
      encountered serotypes for the first time in Turkey. 

PMID- 24852083
TI  - Association analysis identifies new risk loci for non-obstructive azoospermia in
      Chinese men.
AB  - Male factor infertility affects one-sixth of couples worldwide, and non
      obstructive azoospermia (NOA) is one of the most severe forms. Our previous
      genome-wide association study (GWAS) identified three susceptibility loci for NOA
      in Han Chinese men. Here we test promising associations in an extended three
      stage validation using 3,608 NOA cases and 5,909 controls to identify additional
      risk loci. We find strong evidence of three NOA susceptibility loci (P<5.0 * 10(
      8)) at 6p21.32 (rs7194, P=3.76 * 10(-19)), 10q25.3 (rs7099208, P=6.41 * 10(-14))
      and 6p12.2 (rs13206743, P=3.69 * 10(-8)), as well as one locus approaching genome
      wide significance at 1q42.13 (rs3000811, P=7.26 * 10(-8)). In addition, we
      investigate the phenotypic effect of the related gene (gek, orthologous to
      CDC42BPA) at 1q42.13 on male fertility using a Drosophila model. These results
      advance our understanding of the genetic susceptibility to NOA and provide
      insights into its pathogenic mechanism. 

PMID- 24852087
TI  - Efficacy of a thermoexpandable metallic prostate stent (Memokath) in elderly
      patients with urethral obstruction requiring long-term management with urethral
      Foley catheters.
AB  - AIM: To investigate whether the insertion of a thermoexpandable metallic prostate
      stent (Memokath) facilitates the removal of Foley catheters in elderly patients
      ineligible for urethral obstruction surgery because of the potential
      complications involved in long-term catheter management. METHODS: A total of 37
      male patients (mean age 79.8 +/- 6.2 years) ineligible for surgery under general
      anesthesia because of advanced age, the presence of post-cerebrovascular
      disorders or anticoagulant therapy use and who subsequently had a Memokath stent
      inserted between June 2007 and November 2009 were enrolled in the present study.
      Patients with spinal injury were excluded. We compared the correlation between
      prostatic urethral length and total prostate volume (TPV). We also evaluated the
      postoperative postvoid residual (PVR) and presence of pyuria, and reviewed
      postoperative complications and unassisted urination ability. RESULTS: We found a
      positive correlation between prostatic urethral length and TPV. After the
      insertion of the Memokath stent, the catheters were removed from all patients who
      could urinate unassisted. The PVR was <50 mL in 76.4% patients, and there was a
      52% improvement in pyuria after insertion of the Memokath stent. The mean
      postoperative follow-up duration was 33.2 +/- 16.7 months. A total of 21 patients
      (56.7%) were able to urinate unassisted after receiving the Memokath stent.
      Unassisted urination was difficult in patients with poor performance status. No
      serious complications were observed after insertion of the Memokath stent.
      CONCLUSIONS: The Memokath stent was safe and useful for elderly patients with
      urethral obstruction and good performance status requiring long-term management
      with urethral Foley catheters.

PMID- 24852089
TI  - [Bioethical reflections on ill-considered care due to an early diagnosis of
      Alzheimer disease].
AB  - Early diagnosis of Alzheimer disease raises important bioethical issues. In the
      interval between early disease detection and symptom onset, there is a time in
      which the patient's autonomy, privacy, and dignity may be undermined by certain
      healthcare measures or by family care and support. These measures may eventually
      turn patients into an object of care, preventing them from accepting the disease,
      developing an identity, and rearranging their living spaces. Every effort should
      be made to ensure that care does not become compassionate harassment or an
      invasive act, annulling the patient's autonomy, identity, and self-determination.

PMID- 24852088
TI  - CE-ESI-MS for bottom-up proteomics: Advances in separation, interfacing and
      applications.
AB  - With the development of more sensitive hyphenation strategies for capillary
      electrophoresis-electrospray-mass spectrometry the technique has reemerged as
      technique with high separation power combined with high sensitivity in the
      analysis of peptides and protein digests. This review will discuss the newly
      developed hyphenation strategies for CE-ESI-MS and their application in bottom-up
      proteomics as well as the applications in the same time span, 2009 to present,
      using co-axial sheathliquid. Subsequently all separate aspects in the development
      of a CE-ESI-MS method for bottom-up proteomics shall be discussed, highlighting
      certain applications and discussing pros and cons of the various choices. The
      separation of peptides in a capillary electrophoresis system is discussed
      including the great potential for modeling of this migration of peptides due to
      the simple electrophoretic separation process. Furthermore, the technical aspects
      of method development are discussed, namely; background electrolyte choice,
      coating of the separation capillary and chosen loading method. Finally,
      conclusions and an outlook on future developments in the field of bottom-up
      proteomics by CE-ESI-MS will be provided.

PMID- 24852090
TI  - [Opportunity for the integration of the gender perspective in health research and
      innovation in Europe: COST Network genderSTE].
AB  - The European Commission supports several routes for incorporating the gender
      perspective. The Commission currently supports the new Horizon 2020 program, and
      also funds projects such as "gendered innovations", which show how gender
      innovations increase the quality of research and professional practice for health
      and welfare. One of the policy instruments is the Recommendation on Gender,
      Science and Innovation. Against this background, the international European
      Cooperation in Science and Technology (COST) network genderSTE (Gender, Science,
      Technology and Environment) was created, which seeks to: 1) promote structural
      changes in institutions to increase the number of women researchers; 2) identify
      the gender dimensions relevant to the environment; and 3) improve the integration
      of a gender perspective in research and technology. COST GenderSTE supports
      networking and the dissemination of knowledge with a gender perspective. All
      these tools provide an opportunity to incorporate a gender perspective in
      research in Europe. 

PMID- 24852091
TI  - [Exposure to occupational carcinogens among employees protected by prevention
      services outside the province of Salamanca (Spain)].

PMID- 24852092
TI  - Transdermal drug delivery: 30+ years of war and still fighting!
AB  - By any measure, transdermal drug delivery (TDD) is a successful controlled
      release technology. Over the last 30+ years, a steady flux of transdermal
      products have received regulatory approval and reached the market. For the right
      compounds, TDD is an effective and preferred route of administration; for others,
      delivery across the skin makes no sense at all. Currently, the "rules" that
      govern (passive) TDD feasibility are clearly understood, and research activity is
      focused on novel approaches that strive to subvert skin's excellent barrier
      function, and broaden the range of active species amenable to percutaneous
      administration. 

PMID- 24852093
TI  - Perspective and potential of oral lipid-based delivery to optimize
      pharmacological therapies against cardiovascular diseases.
AB  - Cardiovascular diseases (CVDs) remain the major cause of morbidity and mortality
      globally. Despite the large number of cardiovascular drugs available for
      pharmacological therapies, factors limiting the efficient oral use are
      identified, including low water solubility, pre-systemic metabolism, food intake
      effects and short half-life. Numerous in vivo proof-of-concepts studies are
      presented to highlight the viability of lipid-based delivery to optimize the oral
      delivery of cardiovascular drugs. In particular, the key performance enhancement
      roles of oral lipid-based drug delivery systems (LBDDSs) are identified, which
      include i) improving the oral bioavailability, ii) sustaining/controlling drug
      release, iii) improving drug stability, iv) reducing food intake effect, v)
      targeting to injured sites, and vi) potential for combination therapy. Mechanisms
      involved in achieving these features, range of applicability, and limits of
      available systems are detailed. Future research and development efforts to
      address these issues are discussed, which is of significant value in directing
      future research work in fostering translation of lipid-based formulations into
      clinical applications to reduce the prevalence of CVDs.

PMID- 24852094
TI  - Galactose-installed photo-crosslinked pH-sensitive degradable micelles for active
      targeting chemotherapy of hepatocellular carcinoma in mice.
AB  - In this study, we designed and developed galactose-installed photo-crosslinked pH
      sensitive degradable micelles (Gal-CLMs) for active targeting chemotherapy of
      hepatocellular carcinoma in mice. Gal-CLMs were readily obtained from co-self
      assembly of poly(ethylene glycol)-b-poly(mono-2,4,6-trimethoxy benzylidene
      pentaerythritol carbonate-co-acryloyl carbonate) (PEG-b-P(TMBPEC-co-AC)) and Gal
      PEG-b-poly(epsilon-caprolactone) (Gal-PEG-b-PCL) copolymers followed by photo
      crosslinking. Notably, paclitaxel (PTX)-loaded Gal-CLMs (Gal-PTX-CLMs) showed a
      narrow distribution (PDI=0.08-0.12) with average sizes ranging from 92.1 to
      136.3nm depending on the Gal contents. The release of PTX from Gal-CLMs while
      inhibited at physiological pH was enhanced under endosomal pH conditions. MTT
      assays in asialoglycoprotein receptor (ASGP-R) over-expressing HepG2 cells
      demonstrated that half-maximal inhibitory concentration (IC50) values of Gal-PTX
      CLMs decreased from 11.7 to 2.9 to 1.1MUg/mL with increasing Gal contents from
      10% to 20% to 30%, supporting receptor-mediated endocytosis mechanism. The in
      vivo biodistribution studies in human hepatoma SMMC-7721 tumor-bearing nude mice
      displayed that Gal20-PTX-CLMs resulted in significantly enhanced drug
      accumulation in the tumors over non-targeting PTX-CLM counterpart. In accordance,
      Gal20-PTX-CLMs caused much greater tumor growth inhibition than non-targeting PTX
      CLMs as well as non-crosslinking Gal20-PTX-NCLM controls (average tumor volume:
      ca. 35mm(3)versus 144mm(3) and 130mm(3), respectively). Histological analysis
      showed that Gal20-PTX-CLMs induced more extensive apoptosis of tumor cells while
      less damage to normal liver and kidney compared to Taxol. Ligand-installed photo
      crosslinked pH-responsive degradable micelles have a great potential for targeted
      cancer chemotherapy.

PMID- 24852095
TI  - Improving the distribution of Doxil(r) in the tumor matrix by depletion of tumor
      hyaluronan.
AB  - Liposomes improve the pharmacokinetics and safety of rapidly cleared drugs, but
      have not yet improved the clinical efficacy compared to the non-encapsulated
      drug. This inability to improve efficacy may be partially due to the non-uniform
      distribution of liposomes in solid tumors. The tumor extra-cellular matrix is a
      barrier to distribution and includes the high molecular weight glycosaminoglycan,
      hyaluronan (HA). Strategies to remove HA or block its synthesis may improve drug
      delivery into solid tumors. Orally administered methylumbelliferone (MU) is an
      inhibitor of HA synthesis, but it is limited by low potency and limited
      solubility. In this study, we encapsulate a water-soluble phosphorylated prodrug
      of MU (MU-P) in a liposome (L-MU-P). We demonstrate that L-MU-P is a more potent
      inhibitor of HA synthesis than oral MU in the 4T1 murine mammary carcinoma model
      using both a quantitative ELISA and histochemistry. We show that HA depletion
      improves the tumor distribution of liposomes computed using Mander's
      colocalization analysis of liposomes with the tumor vasculature. Hyaluronan
      depletion also increases the fraction of the tumor area positive for liposomes.
      This improved distribution extends the overall survival of mice treated with
      Doxil(r). 

PMID- 24852096
TI  - Injectable multifunctional microgel encapsulating outgrowth endothelial cells and
      growth factors for enhanced neovascularization.
AB  - Recent cell-based therapy approaches have employed both nanotechnologies and
      other biomedical technologies to enhance their therapeutic potential. A combined
      strategy using therapeutic stem/progenitor cells and angiogenic proteins is
      attractive for the treatment of vascular disease. In this study, we developed an
      injectable multifunctional micro-sized gel system (microgel), composed of
      arginine-glycine-aspartic acid (RGD)-conjugated alginate, for the delivery of
      both cells and growth factors in vivo. The microgels encapsulated with outgrowth
      endothelial cells (OECs) and growth factors (vascular endothelial growth factor,
      VEGF, and hepatocyte growth factor, HGF) were formed via electrospraying. Cells
      encapsulated within the microgel exhibited a time-dependent proliferation with
      enhanced cell viability, and the size-controlled microgels resulted in sustained
      release of growth factors for enhanced new vessel formation by tube formation and
      rat aorta sprouting in vitro. Increased angiogenesis was also estimated in mice
      treated with RGD-microgel containing OECs and growth factors. Furthermore,
      injection of the multifunctional microgel into a hindlimb ischemia model improved
      blood flow perfusion and increased the capillary density by histological
      analysis. Compared with hydrogel system, injectable microgel system was shown to
      be superior with no toxicity. Overall, our injectable multifunctional microgel
      system can be attributed to deliver potential therapeutic agents/cells for the
      treatment of vascular diseases. 

PMID- 24852097
TI  - Styrene-maleic acid copolymer-encapsulated CORM2, a water-soluble carbon monoxide
      (CO) donor with a constant CO-releasing property, exhibits therapeutic potential
      for inflammatory bowel disease.
AB  - Carbon monoxide (CO), the physiological product of heme oxygenase during
      catabolic breakdown of heme, has versatile functions and fulfills major anti
      oxidative and anti-apoptotic roles in cell systems. Administration of CO is thus
      thought to be a reasonable therapeutic approach in diseases-such as inflammatory
      bowel disease-that are induced by reactive oxygen species (ROS).
      Tricarbonyldichlororuthenium(II) dimer (CORM2) is a commonly used CO donor, but
      it has poor aqueous solubility and a very short CO-releasing half-life (t1/2). In
      the present study, we prepared micelles consisting of water-soluble styrene
      maleic acid copolymer (SMA) encapsulating CORM2 (SMA/CORM2) that had a
      hydrodynamic size of 165.3nm. Compared with free CORM2, SMA/CORM2 demonstrated
      better water solubility (>50mg/ml in a physiological water solution). Moreover,
      because of micelle formation in an aqueous environment, the CO release rate was
      slow and sustained. These properties resulted in much longer in vivo bioactivity
      of SMA/CORM2 compared with that of free CORM2, i.e. the t1/2 in blood of
      SMA/CORM2 in mice after intravenous (i.v.) injection was about 35 times longer
      than that of free CORM2. We then evaluated the therapeutic potential of SMA/CORM2
      in a murine model of inflammatory colitis induced by dextran sulfate sodium
      (DSS). Administration (either i.v. or oral) of SMA/CORM2 once at the beginning of
      colitis, 3days after DSS treatment, significantly improved colitis symptoms-loss
      of body weight, diarrhea, and hematochezia-as well as histopathological colonic
      changes-shortening of the colon and necrosis or ulcers in the colonic mucosa. Up
      regulation of inflammatory cytokines including monocyte chemotactic protein-1,
      tumor necrosis factor-alpha, and interleukin-6 in this DSS-induced colitis was
      significantly suppressed in SMA/CORM2-treated mice. SMA/CORM2 may thus be a
      superior CO donor and may be a candidate drug, which involves cytokine
      suppression, for ROS-related diseases including inflammatory bowel disease. 

PMID- 24852099
TI  - Ultrasound-enhanced drug delivery in prostate cancer xenografts by nanoparticles
      stabilizing microbubbles.
AB  - The delivery of nanoparticles to solid tumors is often ineffective due to the
      lack of specificity towards tumor tissue, limited transportation of the
      nanoparticles across the vascular wall and poor penetration through the
      extracellular matrix of the tumor. Ultrasound is a promising tool that can
      potentially improve several of the transportation steps, and the interaction
      between sound waves and microbubbles generates biological effects that can be
      beneficial for the successful delivery of nanocarriers and their contents. In
      this study, a novel platform consisting of nanoparticle-stabilized microbubbles
      has been investigated for its potential for ultrasound-enhanced delivery to tumor
      xenografts. Confocal laser scanning microscopy was used to study the supply of
      nanoparticles from the vasculature and to evaluate the effect of different
      ultrasound parameters at a microscopic level. The results demonstrated that
      although the delivery is heterogeneous within tumors, there is a significant
      improvement in the delivery and the microscopic distribution of both
      nanoparticles and a released model drug when the nanoparticles are combined with
      microbubbles and ultrasound. The mechanisms that underlie the improved delivery
      are discussed. 

PMID- 24852098
TI  - A rapamycin-releasing perivascular polymeric sheath produces highly effective
      inhibition of intimal hyperplasia.
AB  - Intimal hyperplasia produces restenosis (re-narrowing) of the vessel lumen
      following vascular intervention. Drugs that inhibit intimal hyperplasia have been
      developed, however there is currently no clinical method of perivascular drug
      delivery to prevent restenosis following open surgical procedures. Here we report
      a poly(epsilon-caprolactone) (PCL) sheath that is highly effective in preventing
      intimal hyperplasia through perivascular delivery of rapamycin. We first screened
      a series of bioresorbable polymers, i.e., poly(lactide-co-glycolide) (PLGA),
      poly(lactic acid) (PLLA), PCL, and their blends, to identify desired release
      kinetics and sheath physical properties. Both PLGA and PLLA sheaths produced
      minimal (<30%) rapamycin release within 50days in PBS buffer. In contrast, PCL
      sheaths exhibited more rapid and near-linear release kinetics, as well as durable
      integrity (>90days) as evidenced in both scanning electron microscopy and
      subcutaneous embedding experiments. Moreover, a PCL sheath deployed around
      balloon-injured rat carotid arteries was associated with a minimum rate of
      thrombosis compared to PLGA and PLLA. Morphometric analysis and
      immunohistochemistry revealed that rapamycin-loaded perivascular PCL sheaths
      produced pronounced (85%) inhibition of intimal hyperplasia (0.15+/-0.05 vs
      1.01+/-0.16), without impairment of the luminal endothelium, the vessel's anti
      thrombotic layer. Our data collectively show that a rapamycin-loaded PCL delivery
      system produces substantial mitigation of neointima, likely due to its favorable
      physical properties leading to a stable yet flexible perivascular sheath and
      steady and prolonged release kinetics. Thus, a PCL sheath may provide useful
      scaffolding for devising effective perivascular drug delivery particularly suited
      for preventing restenosis following open vascular surgery. 

PMID- 24852100
TI  - Defeating the fear: new insights into the neurobiology of stress susceptibility.
AB  - The psychopathological impact of emotional stress on a specific individual varies
      markedly: while most escape the development of post-traumatic stress disorder
      and/or major depression, a select group of individuals demonstrate a
      vulnerability to succumb to these conditions. The past decade has witnessed an
      explosion in animal research into the underlying neurobiological mechanisms that
      govern both vulnerability and resilience to such stressors. In the May 2014
      issue, Chou and colleagues employ the mouse social defeat model of chronic stress
      to demonstrate that defeated susceptible mice display an exaggerated conditioned
      fear response associated with more pronounced autonomic changes. These
      physiological alterations were found to be mediated via local increases in the
      levels of brain derived neurotrophic factor (BDNF) within the basolateral
      amygdala and could be inhibited by the systemic administration of a beta
      adrenergic antagonist. This mini-review critically examines this manuscript's new
      mechanistic insights in light of previous results employing similar approaches.
      The strengths and limitations of the social defeat model, as well as the
      relevance of these findings to neurologic illness are discussed briefly. 

PMID- 24852101
TI  - Angiopoietin-1 ameliorates inflammation-induced vascular leakage and improves
      functional impairment in a rat model of acute experimental autoimmune
      encephalomyelitis.
AB  - Multiple sclerosis (MS) is characterized by perivascular inflammatory
      infiltration, secondary demyelination, and axonal loss in the central nervous
      system. Angiopoietin-1 (Ang-1) constitutes a family of endothelial growth factors
      that can inhibit MS-associated, inflammation-induced blood vascular leakage and
      lessen increased blood vessel permeability. This study was designed to
      investigate the effects of Ang-1 on a model of acute experimental autoimmune
      encephalomyelitis (EAE). Evans blue and the luciferase assay were employed to
      test blood vessel permeability, while immunohistochemistry, ELISA, and Western
      blotting were used to assess the degree of inflammation. Electron microscopy and
      cortical somatosensory evoked potentials were also used to observe axonal loss,
      white matter demyelination, and functional impairment in EAE groups. Our results
      showed that Ang-1 treatment could ameliorate inflammation-induced leakage,
      inhibit inflammatory cell infiltration into the brain and spinal cord, and
      improve functional impairment associated with EAE in a dose-dependent manner. 

PMID- 24852103
TI  - Exome sequencing identifies a recessive PIGN splice site mutation as a cause of
      syndromic congenital diaphragmatic hernia.
AB  - Using exome sequencing we identify a homozygous splice site mutation in the PIGN
      gene in a foetus with multiple congenital anomalies including bilateral
      diaphragmatic hernia, cardiovascular anomalies, segmental renal dysplasia, facial
      dysmorphism, cleft palate, and oligodactyly. This finding expands the phenotypic
      spectrum associated with homozygous loss of function mutations in PIGN, and adds
      further support for defective GPI anchor biosynthesis as a cause of developmental
      abnormalities. We demonstrate that exome sequencing is a valuable approach for
      the identification of a genetic cause in sporadic cases of multiple congenital
      anomalies (MCA) due to inherited mutations. 

PMID- 24852104
TI  - Endoscopic therapy for Kock pouch strictures in patients with inflammatory bowel
      disease.

PMID- 24852102
TI  - Chemokine CXCL1 enhances inflammatory pain and increases NMDA receptor activity
      and COX-2 expression in spinal cord neurons via activation of CXCR2.
AB  - Recent studies have shown that CXCL1 upregulation in spinal astrocytes is
      involved in the maintenance of neuropathic pain. However, whether and how CXCL1
      regulates inflammatory pain remains unknown. Here we show that intraplantar
      injection of CFA increased mRNA and protein expressions of CXCL1 and its major
      receptor CXCR2 in the spinal cord at 6h and 3days after the injection.
      Immunofluorescence double staining showed that CXCL1 and CXCR2 were expressed in
      spinal astrocytes and neurons, respectively. Intrathecal injection of CXCL1
      neutralizing antibody or CXCR2 antagonist SB225002 attenuated CFA-induced
      mechanical and heat hypersensitivity on post-CFA day 3. Patch-clamp recordings
      showed that CXCL1 potentiated NMDA-induced currents in lamina II neurons via
      CXCR2, and this potentiation was further increased in CFA-treated mice.
      Furthermore, intrathecal injection of CXCL1 increased COX-2 expression in dorsal
      horn neurons, which was blocked by pretreatment with SB225002 or MEK (ERK kinase)
      inhibitor PD98059. Finally, pretreatment with SB225002 or PD98059 decreased CFA
      induced heat hyperalgesia and COX-2 mRNA/protein expression and ERK activation in
      the spinal cord. Taken together, our data suggest that CXCL1, upregulated and
      released by spinal astrocytes after inflammation, acts on CXCR2-expressing spinal
      neurons to increase ERK activation, synaptic transmission and COX-2 expression in
      dorsal horn neurons and contributes to the pathogenesis of inflammatory pain. 

PMID- 24852105
TI  - Efficiency of pancreatic duct stenting therapy in children with chronic
      pancreatitis.
AB  - BACKGROUND: Chronic pancreatitis (CP) is a rare disease in childhood. Although
      ERCP is commonly performed in children, the effect of pancreatic duct stenting
      therapy in children with CP is unknown. OBJECTIVE: To investigate the efficacy of
      pancreatic duct stenting in children with CP. DESIGN: Retrospective analysis.
      SETTING: National referral center. PATIENTS: A total of 208 children with CP
      hospitalized between 1988 and 2012. INTERVENTIONS: ERCP with pancreatic duct
      stenting. MAIN OUTCOME MEASUREMENTS: Results of endoscopic therapy and number of
      pancreatitis episodes per year before and after treatment. RESULTS: A total of
      223 pancreatic duct stenting procedures were performed in 72 children. The median
      number of stent replacements was 3 (range 1-21). A statistically significant
      decrease in the number of pancreatitis episodes per year was observed: from 1.75
      to 0.23 after endoscopic treatment (P < .05). Pancreatic duct stenting was
      performed more frequently in patients with hereditary pancreatitis (61.5%) and in
      children with CP and anatomic anomalies of the pancreatic duct (65%; P < .05).
      LIMITATIONS: Retrospective analysis with the assessment of adverse events based
      on medical history. CONCLUSION: Pancreatic duct stenting therapy is a safe and
      effective procedure in children with CP. This therapy should be recommended
      especially for children with hereditary pancreatitis and patients with anatomic
      anomalies of the pancreatic duct.

PMID- 24852106
TI  - Development of a swine bile duct dilation model using endoclips or a detachable
      snare under cap-assisted endoscopy.
AB  - BACKGROUND: A reproducible large animal model of bile duct dilation for the
      preclinical testing of new biliary devices and for training endoscopic biliary
      intervention is required. Surgical methods are mainly used to produce large
      animal models of biliary obstruction. OBJECTIVE: To develop an animal model of
      bile duct dilation using endoscopic methods and to compare the merits of
      endoclips and detachable snares for the obstruction of major duodenal papillae.
      DESIGN: Proof of concept experimental study. SETTINGS: Animal laboratory.
      INTERVENTIONS: Endoscopic clipping of the major duodenal papilla or closure of
      the major duodenal papilla with a detachable snare. MAIN OUTCOME MEASUREMENTS:
      Feasibility, efficacy, and safety of endoscopic methods to develop swine models
      with bile duct dilation were estimated by degree of dilation at the common bile
      duct (CBD), intrahepatic duct (IHD), and gallbladder (GB). RESULTS: All animals
      survived until the end of the experiment. Clipping of the major duodenal papilla
      and closure of the major duodenal papilla with a detachable snare were performed
      successfully in all swine. No technical difficulty or adverse event occurred
      during the procedures. Biliary dilatations in all animals were observed on
      cholangiograms (mean Delta% of postprocedural and preprocedural maximum
      diameters: CBD, 301%; IHD, 223.5%; GB, 34.8%). Degree of bile duct dilation in
      the snare group tended to be greater (CBD, 367.3%; IHD, 298.3%; GB, 47.8%) than
      in the endoclip group (CBD, 234.7%; IHD, 148.7%; GB, 21.8%), but this difference
      was not significant. An analysis of degrees of dilation according to location in
      the biliary tree showed that the GB was not dilated as well as the CBD or IHD.
      LIMITATIONS: Animal model. CONCLUSION: The 2 endoscopic procedures described are
      effective and safe for creating a swine model of bile duct dilation and could be
      helpful for training biliary intervention and for endoscopic biliary studies.

PMID- 24852108
TI  - Twentieth WFN World Congress on Parkinson's disease and related disorders.

PMID- 24852107
TI  - Reprint of: Environments of B cell development.
AB  - B lymphocyte development in the mouse begins with the generation of long-term
      reconstituting, pluripotent hematopoietic stem cells, over multipotent
      myeloid/lymphoid progenitors and common lymphoid progenitors to B-lineage
      committed pro/pre B and pre B cells, which first express pre B cell receptors and
      then immunoglobulins, B cell receptors, to generate the repertoires of peripheral
      B cells. This development is influenced and guided by cells of non-hematopoietic
      and hematopoietic origins. We review here some of the recent developments, and
      our contributions in this fascinating field of developmental immunology. 

PMID- 24852109
TI  - A combined spectroscopic and molecular docking approach to characterize binding
      interaction of megestrol acetate with bovine serum albumin.
AB  - The binding interactions between megestrol acetate (MA) and bovine serum albumin
      (BSA) under simulated physiological conditions (pH 7.4) were investigated by
      fluorescence spectroscopy, circular dichroism and molecular modeling. The results
      revealed that the intrinsic fluorescence of BSA was quenched by MA due to
      formation of the MA-BSA complex, which was rationalized in terms of a static
      quenching procedure. The binding constant (Kb ) and number of binding sites (n)
      for MA binding to BSA were 2.8 * 10(5)  L/mol at 310 K and about 1 respectively.
      However, the binding of MA with BSA was a spontaneous process due to the negative
      ?G(0) in the binding process. The enthalpy change (?H(0) ) and entropy change
      (?S(0) ) were - 124.0 kJ/mol and -295.6 J/mol per K, respectively, indicating
      that the major interaction forces in the binding process of MA with BSA were van
      der Waals forces and hydrogen bonding. Based on the results of spectroscopic and
      molecular docking experiments, it can be deduced that MA inserts into the
      hydrophobic pocket located in subdomain IIIA (site II) of BSA. The binding of MA
      to BSA leads to a slight change in conformation of BSA but the BSA retained its
      secondary structure, while conformation of the MA has significant change after
      forming MA-BSA complex, suggesting that flexibility of the MA molecule supports
      the binding interaction of BSA with MA.

PMID- 24852111
TI  - Can the quantity of cell-free fetal DNA predict preeclampsia: a systematic
      review.
AB  - OBJECTIVE: Previous studies have demonstrated an increase in the quantity of cell
      free fetal DNA (cffDNA) before the onset of preeclampsia. It would be beneficial
      if the quantity of cffDNA predicted preeclampsia in order to implement
      preventative trials and strategies to decrease maternal and fetal morbidity. Our
      objective was to review the literature on using cffDNA levels as a predictor of
      preeclampsia. METHODS: We performed a systematic review following the Meta
      analyses and Systematic Review of Observational Studies guidelines. Included
      studies evaluated cffDNA levels in pregnant women before the clinical onset of
      preeclampsia. RESULTS: Thirteen studies met inclusion criteria. There was
      considerable heterogeneity between included studies, and all received a quality
      grade of C on the Grading of Recommendations Assessment, Development, and
      Evaluation scale. Of the 13 studies, 11 found an increase in cffDNA among
      pregnant women who subsequently developed preeclampsia. In addition, all four
      studies analyzing early-onset or severe preeclampsia found significantly elevated
      cffDNA levels prior to disease onset. CONCLUSION: Cell-free fetal DNA
      quantification is a promising marker for preeclampsia prediction, especially for
      the development of early-onset or severe preeclampsia. However, because of the
      heterogeneity in published studies, a precise conclusion about the statistical
      and clinical relevance cannot be made.

PMID- 24852113
TI  - Direct arylation of pyridines without the use of a transition metal catalyst.
AB  - A method for achieving the direct arylation of pyridines with phenylhydrazine
      hydrochloride was developed in this study. This new reaction proceeds readily at
      room temperature without the use of any transition metal catalysts. This method
      allows rapid access to various arylated heterocycles that are more difficult to
      access through traditional methods. 

PMID- 24852112
TI  - Spectroscopic properties and energy transfer parameters of Er3+-doped
      fluorozirconate and oxyfluoroaluminate glasses.
AB  - Er3+-doped fluorozirconate (ZrF4-BaF2-YF3-AlF3) and oxyfluoroaluminate glasses
      are successfully prepared here. These glasses exhibit significant superiority
      compared with traditional fluorozirconate glass (ZrF4-BaF2-LaF3-AlF3-NaF) because
      of their higher temperature of glass transition and better resistance to water
      corrosion. Judd-Ofelt (J-O) intensity parameters are evaluated and used to
      compute the radiative properties based on the VIS-NIR absorption spectra. Broad
      emission bands located at 1535 and 2708 nm are observed, and large calculated
      emission sections are obtained. The intensity of 2708 nm emission closely relates
      to the phonon energy of host glass. A lower phonon energy leads to a more
      intensive 2708 nm emission. The energy transfer processes of Er3+ ions are
      discussed and lifetime of Er3+:4I13/2 is measured. It is the first time to
      observe that a longer lifetime of the 4I13/2 level leads to a less intensive 1535
      nm emission, because the lifetime is long enough to generate excited state
      absorption (ESA) and energy transfer (ET) processes. These results indicate that
      the novel glasses possess better chemical and thermal properties as well as
      excellent optical properties compared with ZBLAN glass. These Er3+-doped ZBYA and
      oxyfluoroaluminate glasses have potential applications as laser materials.

PMID- 24852114
TI  - Subjective and objective binge eating in relation to eating disorder
      symptomatology, depressive symptoms, and self-esteem among treatment-seeking
      adolescents with bulimia nervosa.
AB  - This study investigated the importance of the distinction between objective (OBE)
      and subjective binge eating (SBE) among 80 treatment-seeking adolescents with
      bulimia nervosa. We explored relationships among OBEs, SBEs, eating disorder (ED)
      symptomatology, depression, and self-esteem using two approaches. Group
      comparisons showed that OBE and SBE groups did not differ on ED symptoms or self
      esteem; however, the SBE group had significantly greater depression. Examining
      continuous variables, OBEs (not SBEs) accounted for significant unique variance
      in global ED pathology, vomiting, and self-esteem. SBEs (not OBEs) accounted for
      significant unique variance in restraint and depression. Both OBEs and SBEs
      accounted for significant unique variance in eating concern; neither accounted
      for unique variance in weight/shape concern, laxative use, diuretic use, or
      driven exercise. Loss of control, rather than amount of food, may be most
      important in defining binge eating. Additionally, OBEs may indicate broader ED
      pathology, while SBEs may indicate restrictive/depressive symptomatology.

PMID- 24852115
TI  - An exact solution for R2,eff in CPMG experiments in the case of two site chemical
      exchange.
AB  - The Carr-Purcell-Meiboom-Gill (CPMG) experiment is widely used to quantitatively
      analyse the effects of chemical exchange on NMR spectra. In a CPMG experiment,
      the effective transverse relaxation rate, R2,eff, is typically measured as a
      function of the pulse frequency, nuCPMG. Here, an exact expression for how R2,eff
      varies with nuCPMG is derived for the commonly encountered scenario of two-site
      chemical exchange of in-phase magnetisation. This result, summarised in Appendix
      A, generalises a frequently used equation derived by Carver and Richards,
      published in 1972. The expression enables more rapid analysis of CPMG data by
      both speeding up calculation of R2,eff over numerical methods by a factor of ca.
      130, and yields exact derivatives for use in data analysis. Moreover, the
      derivation provides insight into the physical principles behind the experiment. 

PMID- 24852117
TI  - BINGO: targeted therapy for advanced biliary-tract cancer.

PMID- 24852116
TI  - Gemcitabine and oxaliplatin with or without cetuximab in advanced biliary-tract
      cancer (BINGO): a randomised, open-label, non-comparative phase 2 trial.
AB  - BACKGROUND: Gemcitabine plus a platinum-based agent (eg, cisplatin or
      oxaliplatin) is the standard of care for advanced biliary cancers. We
      investigated the addition of cetuximab to chemotherapy in patients with advanced
      biliary cancers. METHODS: In this non-comparative, open-label, randomised phase 2
      trial, we recruited patients with locally advanced (non-resectable) or metastatic
      cholangiocarcinoma, gallbladder carcinoma, or ampullary carcinoma and a WHO
      performance status of 0 or 1 from 18 hospitals across France and Germany.
      Eligible patients were randomly assigned (1:1) centrally with a minimisation
      procedure to first-line treatment with gemcitabine (1000 mg/m(2)) and oxaliplatin
      (100 mg/m(2)) with or without cetuximab (500 mg/m(2)), repeated every 2 weeks
      until disease progression or unacceptable toxicity. Randomisation was stratified
      by centre, primary site of disease, disease stage, and previous treatment with
      curative intent or adjuvant therapy. Investigators who assessed treatment
      response were not masked to group assignment. The primary endpoint was the
      proportion of patients who were progression-free at 4 months, analysed by
      intention to treat. This study is registered with ClinicalTrials.gov, number
      NCT00552149. FINDINGS: Between Oct 10, 2007, and Dec 18, 2009, 76 patients were
      assigned to chemotherapy plus cetuximab and 74 to chemotherapy alone. 48 (63%;
      95% CI 52-74) patients assigned to chemotherapy plus cetuximab and 40 (54%; 43
      65) assigned to chemotherapy alone were progression-free at 4 months. Median
      progression-free survival was 6.1 months (95% CI 5.1-7.6) in the chemotherapy
      plus cetuximab group and 5.5 months (3.7-6.6) in the chemotherapy alone group.
      Median overall survival was 11.0 months (9.1-13.7) in the chemotherapy plus
      cetuximab group and 12.4 months (8.6-16.0) in the chemotherapy alone group. The
      most common grade 3-4 adverse events were peripheral neuropathy (in 18 [24%] of
      76 patients who received chemotherapy plus cetuximab vs ten [15%] of 68 who
      received chemotherapy alone), neutropenia (17 [22%] vs 11 [16%]), and increased
      aminotransferase concentrations (17 [22%] vs ten [15%]). 70 serious adverse
      events were reported in 39 (51%) of 76 patients who received chemotherapy plus
      cetuximab (34 events in 19 [25%] patients were treatment-related), whereas 41
      serious adverse events were reported in 25 (35%) of 71 patients who received
      chemotherapy alone (20 events in 12 [17%] patients were treatment-related). One
      patient died of atypical pneumonia related to treatment in the chemotherapy alone
      group. INTERPRETATION: The addition of cetuximab to gemcitabine and oxaliplatin
      did not seem to enhance the activity of chemotherapy in patients with advanced
      biliary cancer, although it was well tolerated. Gemcitabine and platinum-based
      combination should remain the standard treatment option. FUNDING: Institut
      National du Cancer, Merck Serono.

PMID- 24852119
TI  - Synthesis and structure-activity relationship of cyclopentenone oximes as novel
      inhibitors of the production of tumor necrosis factor-alpha.
AB  - 3-Alkyl-2-aryl-2-cyclopenten-1-one oxime derivatives (1) were studied as a novel
      class of inhibitors of tumor necrosis factor alpha (TNF-alpha) with regard to
      synthesis and in vitro SAR inhibition of TNF-alpha. The in vitro IC50 values of
      these compounds in rat and human peripheral blood mononuclear cells were at the
      sub-micromolar level. 

PMID- 24852118
TI  - Discovery of N-sulfonyl-7-azaindoline derivatives as potent, orally available and
      selective M(4) muscarinic acetylcholine receptor agonists.
AB  - We designed and synthesized novel N-sulfonyl-7-azaindoline derivatives as
      selective M4 muscarinic acetylcholine receptor agonists. Modification of the N
      carbethoxy piperidine moiety of compound 2, an M4 muscarinic acetylcholine
      receptor (mAChR)-preferring agonist, led to compound 1, a selective M4 mAChR
      agonist. Compound 1 showed a highly selective M4 mAChR agonistic activity with
      weak hERG inhibition in vitro. A pharmacokinetic study of compound 1 in vivo
      revealed good bioavailability and brain penetration in rats. Compound 1 reversed
      methamphetamine-induced locomotor hyperactivity in rats (1-10 mg/kg, po).

PMID- 24852120
TI  - Sulfonamide inhibition studies of the beta carbonic anhydrase from Drosophila
      melanogaster.
AB  - An inibition study of the beta-carbonic anhydrase (CA, EC 4.2.1.1) DmBCA from the
      insect Drosophila melanogaster with sulfonamides and sulfamates is reported.
      Among the panel of 40 investigated compounds, the best DmBCA inhibitors were the
      sulfonylated benzenesulfonamides and ethoxzolamide, which showed inhibition
      constants in the range of 65.3-138 nM. Methazolamide and sulthiame were also
      effective inhibitors with KIs ranging between 237 and 249 nM, whereas most of the
      simple aromatic/heterocyclic sulfonamides showed inhibition constants in the
      range of 0.47-6.40 MUM. Topiramate, zonisamide and saccharine did not inhibit
      DmBCA. As orthologs of this mitochondrial CA are found in many insect species
      involved in the spread of various diseases, inhibitors interfering with their
      activity may be of interest for developing insecticides with an alternative
      mechanism of action to the presently used agents, for which many insects
      developed extensive resistance.

PMID- 24852121
TI  - NF-kappaB inhibitory activity of polyoxygenated steroids from the Vietnamese soft
      coral Sarcophyton pauciplicatum.
AB  - Chromatographic purification of the methanolic extract from the soft coral
      Sarcophyton pauciplicatum led to the isolation of three polyhydroxylated steroids
      1-3, including a new compound, sarcopanol A (1). Their structures were elucidated
      by spectroscopic analysis and by comparison of the spectroscopic data with those
      of similar compounds previously reported in literature. The anti-inflammatory
      effects of isolated compounds were evaluated using nuclear factor kappa B (NF
      kappaB) luciferase and reverse transcription polymerase chain reaction (RT-PCR).
      The effect of isolated compounds on cell growth was evaluated by MTS assays.
      Compounds 1 and 2 significantly inhibited TNFalpha/INFgamma-induced NF-kappaB
      transcriptional activity in human keratinocyte (HaCaT) cells in a dose-dependent
      manner, with EC50 values of 8.27+/-3.28 and 26.07+/-5.59 MUM, respectively.
      Furthermore, the transcriptional inhibition of these compounds was confirmed by a
      decrease in cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and
      intercellular adhesion molecule-1 (ICAM-1) gene expression levels in HaCaT cells.

PMID- 24852123
TI  - The effect of dietary supplementation with the natural carotenoids curcumin and
      lutein on pigmentation, oxidative stability and quality of meat from broiler
      chickens affected by a coccidiosis challenge.
AB  - 1. An experiment was performed to evaluate the effectiveness of the antioxidants
      curcumin (CRM) and lutein (LTN) on the quality of meat from coccidiosis-infected
      broilers. A total of 200 one-day-old Arbor Acre chicks were randomly assigned to
      a treatment group with 5 replicates. The treatments included a basal diet without
      carotenoid supplementation (control), with 300 mg/kg CRM, with 300 mg/kg LTN or
      with a combination (C + L) of 150 mg/kg CRM and 150 mg/kg LTN. All chickens were
      challenged with Eimeria maxima at 21 d old. 2. The results revealed that the
      coccidiosis reduced redness of meat, while supplementation with carotenoids
      improved the fresh meat's redness (a*) and yellowness (b*) and contributed to
      colour stability maintenance after storage (1 month at -18 degrees C and 3 d at 4
      degrees C). 3. Coccidiosis did not produce lipid and protein oxidation in fresh
      meat, but after storage for one month, the malondialdehyde levels and carbonyl
      contents were lower in the CRM and C + L birds and the sulfhydryl contents were
      higher in C + L birds. 4. The sodium dodecyl sulphate-polyacrylamide gel
      electrophoresis banding pattern showed equivalent myosin chain fragmentations in
      all treatment groups, whereas lower intensity actin bands were observed in the
      control group (CONT). Moreover, myofibril protein denaturation (differential
      scanning calorimetry) profiles showed a reduction in the CONT myosin and actin
      peaks. Coccidiosis reduced the meat's water holding capacity in non-supplemented
      chicken meat and was improved by natural carotenoid. 5. These results emphasise
      that coccidiosis did not decrease the eating quality of fresh meat, that natural
      carotenoids are efficient antioxidants and that CRM (300 mg/kg) fed individually
      or combined with LTN was the most effective supplemented antioxidant compound.

PMID- 24852122
TI  - Biotin-c10-AppCH2ppA is an effective new chemical proteomics probe for
      diadenosine polyphosphate binding proteins.
AB  - Here we report on the synthesis of a synthetic, stable biotin-c10-AppCH2ppA
      conjugate involving an unusual Cannizzaro reaction step. This conjugate is used
      to bind prospective Ap4A binding proteins from Escherichia coli bacterial cell
      lyzates. Following binding, identities of these proteins are then determined
      smoothly by a process of magnetic bio-panning and electrospray mass spectrometry.
      Protein hits appear to be a definitive set of stress protein related targets.
      While this hit list may not be exclusive, and may vary with the nature of
      sampling conditions and organism status, nevertheless hits do appear to
      correspond with bona fide Ap4A-binding proteins. Therefore these hits represent a
      sound basis on which to construct new hypotheses concerning the cellular
      importance of Ap4A to bacterial cells and the potential biological significance
      of Ap4A-protein binding interactions. 

PMID- 24852124
TI  - Ultrasonographic study of initial size and postnatal growth of kidneys in preterm
      infants.
AB  - BACKGROUND: Preterm birth is known to be associated with risks of impaired
      nephrogenesis. OBJECTIVES: To determine the normal range of renal sizes at birth
      in preterm infants as well as their short-term postnatal renal growth, to assess
      the correlation between initial renal size and growth parameters at birth and to
      compare the initial and serial renal sizes between appropriate-for-gestational
      age (AGA) and small-for-gestational-age (SGA) preterm infants. METHODS: Initial
      ultrasonography (US) was prospectively performed in 125 preterm infants within
      the first 72 h of life and every 2 weeks thereafter until a postmenstrual age
      (PMA) of 37 weeks was reached. Correlation between renal size and growth
      parameters was investigated. Renal lengths of AGA and SGA preterm infants were
      compared with those of age-matched fetuses described in the literature. RESULTS:
      The renal sizes at birth in preterm infants are presented. Multiple regression
      analysis showed the strongest correlation between initial renal size and birth
      weight (p < 0.0001). Initial renal lengths of AGA infants were not significantly
      different from those of age-matched fetuses at >=30 weeks' gestational age (GA),
      whereas those of SGA infants were significantly smaller at >=28 weeks' GA. Serial
      renal lengths of SGA infants were significantly smaller than fetal renal lengths
      at >=30 weeks' GA. CONCLUSION: With US, the normal range of initial renal sizes
      of AGA preterm infants was defined according to GA. In contrast to AGA infants,
      SGA infants showed smaller initial renal sizes and no significant catch-up growth
      until a PMA of 37 weeks.

PMID- 24852125
TI  - Current status of online rating of Australian doctors.
AB  - Online rating of patient satisfaction of their doctor is increasingly common
      worldwide. This study of 4157 ratings of Australian doctors found patients were
      extremely satisfied with their doctor. However, this result was limited by a low
      prevalence of rated doctors and low numbers of ratings per doctor. Further
      studies are needed to determine how online rating will affect future practice for
      all doctors. 

PMID- 24852126
TI  - Assessment of conditioning-specific movement tasks and physical fitness measures
      in talent identified under 16-year-old rugby union players.
AB  - Preparedness to train was assessed using a battery of conditioning-specific
      movement tasks (CSMTs) on a group of talent identified rugby union players (n =
      156; age = 15 +/- 7 years; stature = 176 +/- 7 cm; and mass = 74 +/- 14 kg). In
      addition to explore the link between movement competency and performance, a
      series of standard fitness tests was conducted. Overall the group's CSMTs
      competency ratings were low, but task dependent. The proportion of competent
      players ranged from 14% for a single leg squat to 70% for a double to single leg
      landing. Players were subsequently grouped based on their CSMTs ratings using
      cluster analysis. This analysis classified players on features of the CSMT
      battery that distinguished between groups rather than an arbitrary score. Fitness
      test scores were then compared between the 3 groups identified. The "general low
      competency" group jumped 9.1 cm lower (p = 0.0218), sprinted slower across 10, 20
      and 40 m (range, p = 0.0126-0.0018) and covered 389 m less (p = 0.0105) Yo-Yo
      intermittent recovery level 1 distance compared with the "squat competent group."
      In summary, at this important time before academy selection, most players could
      not competently perform the CSMTs that underpin rugby conditioning and may not be
      prepared for the transition into the "training to compete" stage of the suggested
      long-term athlete development model. For this sample of players, the athlete
      development process may therefore be unnecessarily inhibited. Moreover, our
      observations that competency in some CSMTs may explain better running and jumping
      performances in some players suggest that a focus on monitoring and addressing
      movement competencies during the training to train stage of player development
      should be considered.

PMID- 24852127
TI  - Scaling--which methods best predict performance?
AB  - Athletes with a higher body mass (BM) tend to be stronger, with ratio scaling
      possibly eliminating this effect. The aim of this study was to compare
      relationships between sprint performances with scaled measures of strength and
      power. Fifteen professional rugby league players (age, 26.27 6 3.87 years;
      height, 183.33 6 6.37 cm; BM, 96.86 6 11.49 kg) performed 1 repetition maximum
      back squats, power cleans, squat jumps, and sprints (5, 10, and 20 m). Heavier
      athletes (forward) generated significantly greater absolute levels of power
      during the squat jump (5,659.11 6 710.35 vs.4,740.16 6 558.61 W; p , 0.001);
      however, when power data were scaled no differences were observed. Squat
      performance indicated no differences in absolute ability between the subgroups
      (190.6 6 14.25 vs. 205.7 6 18.35 kg), although the lighter group was
      significantly (p # 0.05) stronger than the heavier group when using ratio and
      allometric methods (2.1 vs. 1.9 kg . kg(-1) and 10.42 vs. 9.87 kg . kg(0.28)),
      respectively. Significant relationships with 5-m sprints were only observed for
      ratio and allometrically scaled power cleans (r = 20.625, p , 0.02; r = 20.675, p
      , 0.02), with similar correlations between allometrically scaled 10-m sprint and
      both back squat and power clean performances. Scaled power clean performances
      were also inversely correlated with 20-m sprints (r = 20.620, r = 20.638, p ,
      0.02). Where differences in absolute strength are apparent between individuals of
      different BM, then the use of scaling is required. Because of the similarity
      between ratio and allometric methods, simple ratio scaling is recommended.

PMID- 24852128
TI  - Large-scale, protection-free synthesis of Se-adenosyl-L-selenomethionine
      analogues and their application as cofactor surrogates of methyltransferases.
AB  - S-adenosyl-L-methionine (SAM) analogues have previously demonstrated their
      utility as chemical reporters of methyltransferases. Here we describe the facile,
      large-scale synthesis of Se-alkyl Se-adenosyl-L-selenomethionine (SeAM) analogues
      and their precursor, Se-adenosyl-L-selenohomocysteine (SeAH). Comparison of SeAM
      analogues with their equivalent SAM analogues suggests that sulfonium-to
      selenonium substitution can enhance their compatibility with certain protein
      methyltransferases, favoring otherwise less reactive SAM analogues. Ready access
      to SeAH therefore enables further application of SeAM analogues as chemical
      reporters of diverse methyltransferases.

PMID- 24852130
TI  - DNA molecular beacon-based plastic biochip: a versatile and sensitive scanometric
      detection platform.
AB  - In this paper, we report a novel DNA molecular beacon (MB)-based plastic biochip
      platform for scanometric detection of a range of analytical targets. Hairpin DNA
      strands, which are dually modified with amino and biotin groups at their two ends
      are immobilized on a disposable plastic (polycarbonate) substrate as recognition
      element and gold nanoparticle-assisted silver-staining as signal reading
      protocol. Initially, the immobilized DNA probes are in their folded forms; upon
      target binding the hairpin secondary structure of the probe strand is "forced"
      open (i.e., converted to the unfolded state). Nanogold-streptavidin conjugates
      can then bind the terminal biotin groups and promote the deposition of rather
      large silver particles which can be either directly visualized or quantified with
      a standard flatbed scanner. We demonstrate that with properly designed probe
      sequences and optimized preparation conditions, a range of molecular targets,
      such as DNA strands, proteins (thrombin) and heavy metal ions (Hg(2+)), can be
      detected with high sensitivity and excellent selectivity. The detection can be
      done in both standard physiological buffers and real world samples. This
      constitutes a platform technology for performing rapid, sensitive, cost
      effective, and point-of-care (POC) chemical analysis and medical diagnosis. 

PMID- 24852129
TI  - HSV-1 ICP0: An E3 Ubiquitin Ligase That Counteracts Host Intrinsic and Innate
      Immunity.
AB  - The herpes simplex virus type 1 (HSV-1) encoded E3 ubiquitin ligase, infected
      cell protein 0 (ICP0), is required for efficient lytic viral replication and
      regulates the switch between the lytic and latent states of HSV-1. As an E3
      ubiquitin ligase, ICP0 directs the proteasomal degradation of several cellular
      targets, allowing the virus to counteract different cellular intrinsic and innate
      immune responses. In this review, we will focus on how ICP0's E3 ubiquitin ligase
      activity inactivates the host intrinsic defenses, such as nuclear domain 10
      (ND10), SUMO, and the DNA damage response to HSV-1 infection. In addition, we
      will examine ICP0's capacity to impair the activation of interferon (innate)
      regulatory mediators that include IFI16 (IFN gamma-inducible protein 16), MyD88
      (myeloid differentiation factor 88), and Mal (MyD88 adaptor-like protein). We
      will also consider how ICP0 allows HSV-1 to evade activation of the NF-kappaB
      (nuclear factor kappa B) inflammatory signaling pathway. Finally, ICP0's
      paradoxical relationship with USP7 (ubiquitin specific protease 7) and its roles
      in intrinsic and innate immune responses to HSV-1 infection will be discussed. 

PMID- 24852132
TI  - Establishment and characterization of a piscean PCF cell line for toxicity and
      gene expression studies as in vitro model.
AB  - A new piscean fibroblastic cell line termed as PCF derived from the caudal fin
      tissue of dark mahseer, Puntius (Tor) chelynoides was established and
      characterized in the present study which was found to be suitable for toxicity
      and gene expression studies as in vitro model. The cell line grew well in
      Leibovitz's L-15 medium supplemented with 10% fetal bovine serum (FBS). The cells
      were able to grow at a temperature ranging from 20 to 28  degrees C with an
      optimal growth at 24  degrees C and the cell line have been expanded in culture
      for more than 70 passages. Authentication of the cell line was carried out using
      mitochondrial DNA markers (Cytochrome Oxidase subunit I and 16S ribosomal RNA).
      Presence of vimentin in the cells confirmed the fibroblastic origin of cell line.
      Significant cytopathic effects were observed upon exposure of PCF cell line to
      bacterial extracellular products and the study also validated the suitability of
      cell line in transgenic applications as well as in genotoxicity assessment as an
      in vitro model.

PMID- 24852131
TI  - Vortioxetine restores reversal learning impaired by 5-HT depletion or chronic
      intermittent cold stress in rats.
AB  - Current treatments for depression, including serotonin-specific reuptake
      inhibitors (SSRIs), are only partially effective, with a high incidence of
      residual symptoms, relapse, and treatment resistance. Loss of cognitive
      flexibility, a component of depression, is associated with dysregulation of the
      prefrontal cortex. Reversal learning, a form of cognitive flexibility, is
      impaired by chronic stress, a risk factor for depression, and the stress-induced
      impairment in reversal learning is sensitive to chronic SSRI treatment, and is
      mimicked by serotonin (5-HT) depletion. Vortioxetine, a novel, multimodal-acting
      antidepressant, is a 5-HT3, 5-HT7 and 5-HT1D receptor antagonist, a 5-HT1B
      receptor partial agonist, a 5-HT1A receptor agonist, and inhibits the 5-HT
      transporter. Using adult male rats, we first investigated the direct effects of
      vortioxetine, acting at post-synaptic 5-HT receptors, on reversal learning that
      was compromised by 5-HT depletion using 4-chloro-DL-phenylalanine methyl ester
      hydrochloride (PCPA), effectively eliminating any contribution of 5-HT reuptake
      blockade. PCPA induced a reversal learning impairment that was alleviated by
      acute or sub-chronic vortioxetine administration, suggesting that post-synaptic 5
      HT receptor activation contributes to the effects of vortioxetine. We then
      investigated the effects of chronic dietary administration of vortioxetine on
      reversal learning that had been compromised in intact animals exposed to chronic
      intermittent cold (CIC) stress, to assess vortioxetine's total pharmacological
      effect. CIC stress impaired reversal learning, and chronic vortioxetine
      administration prevented the reversal-learning deficit. Together, these results
      suggest that the direct effect of vortioxetine at 5-HT receptors may contribute
      to positive effects on cognitive flexibility deficits, and may enhance the effect
      of 5-HT reuptake blockade. 

PMID- 24852133
TI  - The expression of cell cycle related proteins PCNA, Ki67, p27 and p57 in normal
      and preeclamptic human placentas.
AB  - Placenta is a transitional area making many physiological activities between
      mother and fetus and therefore, it is a critical organ influencing the outcome of
      pregnancy. Fetal growth is directly related to placental development. Accurate
      placental development depends on coordinated action of trophoblasts'
      proliferation, differentiation and invasion. Information on cell cycle related
      proteins that control these events is limited and how they are affected in
      preeclampsia is not fully understood yet. Therefore, in this study, in order to
      understand the role of cell cycle regulators in preeclamptic placentas we aimed
      to determine the spatio-temporal immunolocalizations of cell cycle regulators in
      preeclamptic and normal human term placentas. Term placentas were obtained from
      women diagnosed with preeclampsia and from normal pregnancies with informed
      consent following cesarean deliveries. Placental samples were stained via
      immunohistochemistry with PCNA, Ki67, p27, p57, vimentin and cytokeratin 7
      antibodies and were examined by light microscopy. PCNA and Ki67 staining
      intensities significantly increased in villous parts, significantly decreased in
      basal plates of PE group and did not change in chorionic plates. Staining
      intensities of cell cycle inhibitors p27 and p57 significantly increased in all
      parts of preeclamptic placentas compared to control. Placental abnormalities of
      preeclamptic placentas might be associated with proliferation and cell cycle
      arrest mechanisms' alterations occurred in preeclampsia. 

PMID- 24852134
TI  - Evaluation of a levonorgestrel-releasing intrauterine system for treating
      endometrial hyperplasia in patients with polycystic ovary syndrome.
AB  - OBJECTIVE: To evaluate the use of a levonorgestrel-releasing intrauterine system
      (LNG-IUS) for treating endometrial hyperplasia in patients with polycystic ovary
      syndrome (PCOS). METHODS: LNG-IUSs were inserted in 60 PCOS patients with simple
      (40 cases), irregular (12 cases), or complex (8 cases) endometrial hyperplasia.
      Follow-ups were performed at 3, 6, 12, and 24 months after insertion. At each
      time point, changes in menstruation, hemoglobin level, and endometrial thickness
      and pathology were recorded. Menstrual changes were assessed with the Pictorial
      Blood Assessment Chart. Hemoglobin levels were measured by the Blood Routine
      Test. Endometrial thickness was determined by transvaginal ultrasound.
      Endometrial pathology was defined as simple, irregular, or complex endometrial
      hyperplasia by a pathologist after curettage. Outcomes at each time point were
      compared to baseline (pre-insertion) measurements by Student's t test or ANOVA
      (for multiple comparisons) with the post hoc Dunnett's test. Differences with a p
      < 0.05 were considered statistically significant. RESULTS: At all time points
      after LNG-IUS insertion and in all patients, menstrual blood loss was decreased
      and hemoglobin level was increased significantly compared to pre-insertion
      levels. The endometrial thickness was significantly reduced in all groups after
      12 months. Most patients showed transformation of the endometrial pathology, with
      complete disappearance of simple and irregular cases of endometrial hyperplasia
      and a decreased number of complex endometrial hyperplasia cases. CONCLUSIONS: LNG
      IUS is an effective, safe, nonsurgical, and atraumatic approach with few side
      effects for the treatment of endometrial hyperplasia in patients with PCOS.

PMID- 24852135
TI  - Aliphatic polyester block polymers: renewable, degradable, and sustainable.
AB  - Nearly all polymers are derived from nonrenewable fossil resources, and their
      disposal at their end of use presents significant environmental problems.
      Nonetheless, polymers are ubiquitous, key components in myriad technologies and
      are simply indispensible for modern society. An important overarching goal in
      contemporary polymer research is to develop sustainable alternatives to "petro
      polymers" that have competitive performance properties and price, are derived
      from renewable resources, and may be easily and safely recycled or degraded.
      Aliphatic polyesters are particularly attractive targets that may be prepared in
      highly controlled fashion by ring-opening polymerization of bioderived lactones.
      However, property profiles of polyesters derived from single monomers
      (homopolymers) can limit their applications, thus demanding alternative
      strategies. One such strategy is to link distinct polymeric segments in an A-B-A
      fashion, with A and B chosen to be thermodynamically incompatible so that they
      can self-organize on a nanometer-length scale and adopt morphologies that endow
      them with tunable properties. For example, such triblock copolymers can be useful
      as thermoplastic elastomers, in pressure sensitive adhesive formulations, and as
      toughening modifiers. Inspired by the tremendous utility of petroleum-derived
      styrenic triblock copolymers, we aimed to develop syntheses and understand the
      structure-property profiles of sustainable alternatives, focusing on all
      renewable and all readily degradable aliphatic polyester triblocks as targets.
      Building upon oxidation chemistry reported more than a century ago, a constituent
      of the peppermint plant, (-)-menthol, was converted to the epsilon-caprolactone
      derivative menthide. Using a diol initiator and controlled catalysis, menthide
      was polymerized to yield a low glass transition temperature telechelic polymer
      (PM) that was then further functionalized using the biomass-derived monomer
      lactide (LA) to yield fully renewable PLA-PM-PLA triblock copolymers. These new
      materials were microphase-separated and could be fashioned as high-performing
      thermoplastic elastomers, with properties comparable to commercial styrenic
      triblock copolymers. Examination of their hydrolytic degradation (pH 7.4, 37 
      degrees C) revealed retention of properties over a significant period, indicating
      potential utility in biomedical devices. In addition, they were shown to be
      useful in pressure-sensitive adhesives formulations and as nucleating agents for
      crystallization of commercially relevant PLA. More recently, new triblocks have
      been prepared through variation of each of the segments. The natural product
      alpha-methylene-gamma-butyrolactone (MBL) was used to prepare triblocks with
      poly(alpha-methylene-gamma-butyrolactone) (PMBL) end blocks, PMBL-PM-PMBL. These
      materials exibited impressive mechanical properties that were largely retained at
      100  degrees C, thus offering application advantages over triblock copolymers
      comprising poly(styrene) end blocks. In addition, replacements for PM were
      explored, including the polymer derived from 6-methyl caprolactone (MCL). In sum,
      success in the synthesis of fully renewable and degradable ABA triblock
      copolymers with useful properties was realized. This approach has great promise
      for the development of new, sustainable polymeric materials as viable
      alternatives to nonrenewable petroleum-derived polymers in numerous applications.

PMID- 24852137
TI  - The role of acrylonitrile in controlling the structure and properties of
      nanostructured ionomer films.
AB  - Ionomers are polymers which contain ionic groups that are covalently bound to the
      main chain. The presence of a small percentage of ionic groups strongly affects
      the polymer's mechanical properties. Here, we examine a new family of
      nanostructured ionomer films prepared from core-shell polymer nanoparticles
      containing acrylonitrile (AN), 1,3-butadiene (Bd) and methacrylic acid (MAA).
      Three new AN-containing dispersions were investigated in this study. The core
      shell nanoparticles contained a PBd core. The shells contained copolymerised Bd,
      AN and MAA, i.e., PBd-AN-MAA. Three types of crosslinking were present in these
      films: covalent crosslinks (from Bd); strong physical crosslinks (involving ionic
      bonding of RCOO(-) and Zn(2+)) and weaker physical crosslinks (from AN). We
      examined and compared the roles of AN and ionic crosslinking (from added Zn(2+))
      on the structure and mechanical properties of the films. The FTIR spectroscopy
      data showed evidence for RCOOH-nitrile hydrogen bonding with tetrahedral
      geometry. DMTA studies showed that AN copolymerised within the PBd-AN-MAA phase
      uniformly. Tensile stress-strain data showed that inclusion of AN increased
      elasticity and toughness. Analysis showed that about 33 AN groups were required
      to provide an elastically-effective chain. However, only 1.5 to 2 ionically
      bonded RCOO(-) groups were required to generate an elastically-effective chain.
      By contrast to ionic bonding, AN inclusion increased the modulus without
      compromising ductility. Our results show that AN is an attractive, versatile,
      monomer for increasing the toughness of nanostructured ionomers and this should
      also be the case for other nanostructured polymer elastomers. 

PMID- 24852136
TI  - Human papillomavirus type 16 viral load in relation to HIV infection, cervical
      neoplasia and cancer in Senegal.
AB  - BACKGROUND: The importance of human papillomavirus (HPV) viral load in the
      pathogenesis of cervical cancer among HIV-infected and HIV-uninfected women has
      not yet been established. METHODS: In this cross-sectional study, HPV-16 viral
      loads were measured using previously-collected and frozen cervical swab samples
      from 498 HPV-16 positive Senegalese women (368 HIV-seronegative, 126 HIV-1 and/or
      HIV-2 seropositive). The real-time polymerase chain reaction assay was used to
      quantify HPV-16 E7 copy number normalized by human cellular DNA (beta-actin), and
      viral loads were log10 transformed. Associations between HPV-16 viral load,
      degree of cervical abnormality, and HIV status were assessed using multinomial
      and linear regression methods. RESULTS: Compared to women with normal cytology,
      the likelihood of CIN1 (ORa: 1.21, 95% CI 0.93-1.57), CIN2-3 (ORa: 2.38, 95% CI
      1.72-3.29) and cancer (ORa: 2.12, 95% CI 1.52-2.96) was found to increase for
      each 1-unit log10 increase in HPV-16 viral load. Compared to HIV-negative women,
      HIV-positive women had higher average HPV-16 viral load values (betaa: 0.39, 95%
      CI 0.03-0.75), even after accounting for degree of cervical abnormality.
      CONCLUSION: In our study of women including those with cancer, HPV-16 viral load
      was associated with a higher likelihood of cervical abnormalities. However,
      substantial overlaps across categories of disease severity existed. Higher viral
      load among HIV-infected individuals may indicate that HIV infection influences
      HPV viral replication factors.

PMID- 24852138
TI  - Acute appendicitis in organ transplantation patients: a report of two cases and a
      literature review.
AB  - BACKGROUND: Abdominal surgery on patients with previous organ transplantation,
      especially in the early postoperative period, is a challenging problem. Due to
      high risk of complications in transplant patients, we usually tend to treat such
      patients more conservatively rather compared to the more aggressive attitude in
      diagnosis and surgery of non-transplant patients. Delayed diagnosis, delayed
      surgery, and high morbidity and mortality are more common in transplant patients
      with GI disease. While appendicitis is one of the most common surgical diseases,
      with an estimated lifetime risk of 8.6% for males and 6.7% for females, there are
      relatively few reports of appendicitis in solid organ transplant recipients, and
      the condition has rarely been reported after liver transplantation. CASE REPORT:
      We have performed surgery on 2 cases of presumed acute appendicitis among 75
      cases of kidney and liver transplantation in our series in the last 10 years.
      Laparoscopic technique was used for exploration of presumed acute appendicitis
      with atypical clinical and image presentation in a deceased donor liver
      transplantation (DDLT) and a deceased donor kidney transplantation (DDKT).
      CONCLUSIONS: Acute appendicitis in both patients was highly suspected
      preoperatively in computed tomography, and early exploration with laparoscopic
      technique prompted early diagnosis and treatment, with excellent surgical
      outcomes.

PMID- 24852139
TI  - Gender differences in health-related quality of life of Korean patients with
      chronic obstructive lung disease.
AB  - OBJECTIVES: The aim of this study was to identify the health-related quality of
      life (HRQOL) of COPD patients over 40 years of age in Korea and to assess the
      relevance of gender differences. DESIGN AND SAMPLE: Original data from KNHANES
      (Korea National Health and Nutrition Examination Survey) were analyzed using SAS
      9.3 software. The sample comprised 556 male and 195 female COPD patients.
      MEASURES: Selected demographic variables, HRQOL [EuroQol 5-Dimension], physical
      and psychological characteristics, and health-related characteristics were
      examined. RESULTS: The results showed that the HRQOL of COPD patients was better
      for females than for males, and that the HRQOL among males differed with the
      education, economic activity, economic level, blood pressure, suicidal ideation,
      and physical activity, while among females it differed with age, living status,
      education, economic activity, economic level, blood pressure, stress recognition,
      suicidal ideation, alcohol use, and physical activity. Further analysis verified
      that for males, the education, suicidal ideation, and physical activity were
      factors that affected HRQOL (R(2) = 0.139, p < .001), while for females these
      factors were the education, obesity, and suicidal ideation (R(2) = 0.340, p <
      .001). CONCLUSION: Effective-health promoting interventions for COPD patients
      require the development of individualized programs that take into account gender
      related factors that can enhance HRQOL.

PMID- 24852140
TI  - Mouse lung infection model to assess Rhodococcus equi virulence and vaccine
      protection.
AB  - The pathogenic actinomycete Rhodococcus equi causes severe purulent lung
      infections in foals and immunocompromised people. Although relatively
      unsusceptible to R. equi, mice are widely used for in vivo studies with this
      pathogen. The most commonly employed mouse model is based on systemic
      (intravenous) infection and determination of R. equi burdens in spleen and liver.
      Here, we investigated the murine lung for experimental infection studies with R.
      equi. Using a 10(7)CFU intranasal challenge in BALB/c mice, virulent R. equi
      consistently survived in quantifiable numbers up to 10 days in the lungs whereas
      virulence-deficient R. equi bacteria were rapidly cleared. An internally
      controlled virulence assay was developed in which the test R. equi strains are co
      inoculated and monitored in the same mouse. Isogenic R. equi bacteria lacking
      either the plasmid vapA gene or the entire virulence plasmid were compared using
      this competitive assay. Both strains showed no significant differences in in vivo
      fitness in the lung, indicating that the single loss of the virulence factor VapA
      was sufficient to account for the full attenuation seen in the absence of the
      virulence plasmid. To test the adequacy of the lung infection model for
      monitoring R. equi vaccine efficacy, BALB/c mice were immunized with live R. equi
      and challenged intranasally. Vaccination conferred protection against acute
      pulmonary challenge with virulent R. equi. Our data indicate that the murine lung
      infection model provides a useful tool for both R. equi virulence and vaccine
      studies. 

PMID- 24852141
TI  - Antimicrobial resistance in bacteria from animals and the environment.

PMID- 24852142
TI  - Resistance to hepatitis C virus protease inhibitors.
AB  - Significant scientific advances have enabled the development of new classes of
      antivirals for the treatment of HCV. Protease inhibitors were the first approved,
      achieving substantially higher response rates, with shorter treatment durations,
      in the majority of genotype 1 infected patients. However, in patients who fail
      treatment, drug resistant variants frequently emerge. The pattern of resistant
      variants observed is a result of the specific inhibitor, viral subtype, and level
      of drug selective pressure. Data suggest the replacement of these variants over
      time; however, retreatment of these patients is an area of needed investigation.
      As multiple drug classes progress in development, combinations of agents improve
      treatment success, increase the genetic barrier to resistance, and provide
      shorter treatment durations for diverse patient populations. 

PMID- 24852144
TI  - Bilateral subfoveal neurosensory retinal detachment associated with MEK inhibitor
      use for metastatic cancer.
AB  - IMPORTANCE: Bilateral central serous retinopathy-like events have been described
      in patients receiving drugs that inhibit the mitogen-activated protein kinase
      enzyme MEK for metastatic cancer. To date, the clinical details of this ocular
      adverse effect have not been adequately described in the literature. We report on
      a series of bilateral subfoveal neurosensory retinal detachments in patients with
      metastatic cancer undergoing systemic therapy with MEK inhibitors enrolled in
      clinical trials at our center. OBSERVATIONS: The clinical records of all patients
      with metastatic cancer enrolled in clinical trials requiring protocol
      ophthalmologic evaluation at our center were reviewed. Patients were excluded if
      they were receiving a non-MEK inhibitor, such as a BRAF inhibitor. Results of
      visual acuity and ophthalmic diagnostic tests, as well as clinical course and
      management, were determined. Three patients who received oral MEK inhibitors
      developed bilateral subfoveal neurosensory retinal detachment. Patient 1 had
      metastatic uveal melanoma; the findings resolved without intervention, and
      subsequent mild uveitis was responsive to topical corticosteroids. Patient 2 had
      metastatic cholangiocarcinoma, and his findings resolved after 2 weeks of
      observation. Patient 3 had metastatic rectal cancer, with bilateral uveitis and
      bilateral subfoveal retinal detachment. Her findings resolved with observation
      and topical corticosteroids for uveitis. No patient developed permanent ocular
      sequelae, and none withdrew from the clinical trial of MEK inhibitor therapy.
      CONCLUSIONS AND RELEVANCE: In this series, we report the detailed clinical
      findings of bilateral subfoveal neurosensory retinal detachment associated with
      MEK inhibitor use for treatment of metastatic cancer. A clinical finding of
      uveitis may prompt the ophthalmologist to consider subfoveal neurosensory retinal
      detachment.

PMID- 24852143
TI  - Hydrogen sulfide deactivates common nitrobenzofurazan-based fluorescent thiol
      labeling reagents.
AB  - Sulfhydryl-containing compounds, including thiols and hydrogen sulfide (H2S),
      play important but differential roles in biological structure and function. One
      major challenge in separating the biological roles of thiols and H2S is
      developing tools to effectively separate the reactivity of these sulfhydryl
      containing compounds. To address this challenge, we report the differential
      responses of common electrophilic fluorescent thiol labeling reagents, including
      nitrobenzofurazan-based scaffolds, maleimides, alkylating agents, and
      electrophilic aldehydes, toward cysteine and H2S. Although H2S reacted with all
      of the investigated scaffolds, the photophysical response to each scaffold was
      significantly different. Maleimide-based, alkylating, and aldehydic thiol
      labeling reagents provided a diminished fluorescence response when treated with
      H2S. By contrast, nitrobenzofurazan-based labeling reagents were deactivated by
      H2S addition. Furthermore, the addition of H2S to thiol-activated
      nitrobenzofurazan-based reagents reduced the fluorescence signal, thus
      establishing the incompatibility of nitrobenzofurazan-based thiol labeling
      reagents in the presence of H2S. Taken together, these studies highlight the
      differential reactivity of thiols and H2S toward common thiol-labeling reagents
      and suggest that sufficient care must be taken when labeling or measuring thiols
      in cellular environments that produce H2S due to the potential for both false
      positive and eroded responses. 

PMID- 24852145
TI  - A MU analysis-based, controller-synthesis framework for robust bioinspired visual
      navigation in less-structured environments.
AB  - Safe, autonomous navigation by aerial microsystems in less-structured
      environments is a difficult challenge to overcome with current technology. This
      paper presents a novel visual-navigation approach that combines bioinspired wide
      field processing of optic flow information with control-theoretic tools for
      synthesis of closed loop systems, resulting in robustness and performance
      guarantees. Structured singular value analysis is used to synthesize a dynamic
      controller that provides good tracking performance in uncertain environments
      without resorting to explicit pose estimation or extraction of a detailed
      environmental depth map. Experimental results with a quadrotor demonstrate the
      vehicle's robust obstacle-avoidance behaviour in a straight line corridor, an S
      shaped corridor and a corridor with obstacles distributed in the vehicle's path.
      The computational efficiency and simplicity of the current approach offers a
      promising alternative to satisfying the payload, power and bandwidth constraints
      imposed by aerial microsystems. 

PMID- 24852146
TI  - BAG6/BAT3 modulates autophagy by affecting EP300/p300 intracellular localization.
AB  - We recently reported that BAG6/BAT3 (BCL2-associated athanogene 6) is essential
      for basal and starvation-induced autophagy in E18.5 bag6(-/-) mouse embryos and
      in mouse embryonic fibroblasts (MEFs) through the modulation of the EP300/p300
      dependent acetylation of TRP53 and autophagy-related (ATG) proteins. We observed
      that BAG6 increases TRP53 acetylation during starvation and pro-autophagic TRP53
      target gene expression. BAG6 also decreases the EP300 dependent-acetylation of
      ATG5, ATG7, and LC3-I, posttranslational modifications that inhibit autophagy. In
      addition, in the absence of BAG6 or when using a mutant of BAG6 exclusively
      located in the cytoplasm, autophagy is inhibited, ATG7 is hyperacetylated, TRP53
      acetylation is abrogated, and EP300 accumulates in the cytoplasm indicating that
      BAG6 is involved in the regulation of the nuclear localization of EP300. We also
      reported that the interaction between BAG6 and EP300 occurs in the cytoplasm
      rather than the nucleus. Moreover, during starvation, EP300 is transported to the
      nucleus in a BAG6-dependent manner. We concluded that BAG6 regulates autophagy by
      controlling the localization of EP300 and its accessibility to nuclear (TRP53)
      and cytoplasmic (ATGs) substrates. 

PMID- 24852147
TI  - A child's vision.
AB  - Implementing standard vision screening techniques in the primary care practice is
      the most effective means to detect children with potential vision problems at an
      age when the vision loss may be treatable. A critical period of vision
      development occurs in the first few weeks of life; thus, it is imperative that
      serious problems are detected at this time. Although it is not possible to
      quantitate an infant's vision, evaluating ocular health appropriately can mean
      the difference between sight and blindness and, in the case of retinoblastoma,
      life or death. 

PMID- 24852148
TI  - Amblyopia.
AB  - Amblyopia refers to unilateral or bilateral reduction in best corrected visual
      acuity, not directly attributed to structural abnormality of the eye or posterior
      visual pathways. Early detection of amblyopia is crucial to obtaining the best
      response to treatment. Amblyopia responds best to treatment in the first few
      years of life. In the past several years a series of studies undertaken by the
      Pediatric Eye Disease Investigator Group (PEDIG) have been designed to evaluate
      traditional methods for treating amblyopia and provide evidence on which to base
      treatment decisions. This article summarizes and discusses the findings of the
      PEDIG studies to date. 

PMID- 24852149
TI  - Pediatric refractive surgery.
AB  - This article reviews current thoughts regarding pediatric refractive surgery.
      This encompasses current trends in adult refractive surgery, differences between
      adult and pediatric refractive surgery, and future possibilities for refractive
      technology for the pediatric population. 

PMID- 24852150
TI  - The lacrimal system.
AB  - The lacrimal system comprises of a series of anatomical structures with specific
      physiologic properties. Tearing from a nasolacrimal duct obstruction (NLDO) is
      the most common lacrimal system abnormality encountered by pediatric
      ophthalmologists. Most NLDOs spontaneously improve with conservative management
      by 12 months of age, but persistent or atypical cases may be treated with a
      procedure consisting of probing and irrigation of the lacrimal system. Other less
      common but significant lacrimal system abnormalities are also discussed. 

PMID- 24852151
TI  - Periocular hemangiomas and lymphangiomas.
AB  - Infantile hemangiomas are the most common benign tumor of childhood.
      Lymphangiomas are benign hamartomatous vascular tumors. Both lesions can be
      problematic when located in the periocular region. Pediatricians must be familiar
      with the characteristics of each which would necessitate referral to an
      ophthalmologist or other subspecialist for evaluation, including obstruction of
      the visual axis which can lead to amblyopia of the affected eye. Additional
      potential complications include proptosis, ocular motility limitation, optic
      nerve injury, and poor eyelid closure with or without corneal surface disease.
      All children with periocular hemangiomas or lymphangiomas should be referred to
      an ophthalmologist for further evaluation. 

PMID- 24852152
TI  - Genetics and ocular disorders: a focused review.
AB  - Increasingly accurate phenotyping leads to better genetic evaluation. Genetic eye
      conditions may be due to a common cellar defect (eg, ciliopathies or
      RASopathies). Early-onset retinal dystrophies may be associated with renal
      disease. An understanding of genetic testing helps clinicians identify
      shortcomings in testing which may lead to a better understanding of the most
      appropriate test for a given ocular condition. Dedicated genetic counselors
      within ophthalmic and pediatric clinics are likely to improve the delivery of
      clinical care in these settings. 

PMID- 24852153
TI  - Retinopathy of prematurity.
AB  - Premature infants born at 30 weeks' gestational age or younger, or 1500 g or
      smaller, are screened for retinopathy of prematurity (ROP). Guidelines for
      supplemental oxygen in neonatal intensive care units have decreased but not
      eliminated the incidence of severe ROP. The underlying cause for ROP is
      prematurity and low birth weight, and with the survival of smaller and younger
      babies, ROP continues to be a significant problem facing premature infants.
      Threshold ROP is treated with retinal photocoagulation, but newer treatments such
      as intraocular injections of bevacizumab (Avastin) are being used alone or in
      conjunction with laser. 

PMID- 24852154
TI  - A review of pediatric idiopathic intracranial hypertension.
AB  - It is now well recognized that idiopathic intracranial hypertension (IIH) can
      occur in children. Relative to the adult population, the demographic features and
      clinical presentation of IIH as well as the diagnosis and treatment guidelines
      for children are quite different. Although these differences are well
      established, specific diagnostic and treatment guidelines for pediatric patients
      have largely been based on the adult literature. Exciting new evidence is now
      available to assist the clinician in managing pediatric patients with IIH. 

PMID- 24852155
TI  - The pediatric red eye.
AB  - There is a broad differential for the pediatric red eye, which may range from
      benign conditions to vision- and/or life-threatening conditions. This article
      presents a systematic differential, red flags for referral, and treatment
      options. 

PMID- 24852156
TI  - Allergic eye disease.
AB  - Ocular allergy is one of the most common conditions encountered by pediatricians
      and ophthalmologists and is characterized by bilateral injection with itching as
      the predominant symptom. Risk factors include history of atopy (asthma, eczema,
      seasonal allergies). Basic and clinical research have provided insight into the
      immunologic mechanisms, clinical presentation, differential diagnosis, and
      pharmacologicmanagement of this condition. New pharmacologic agents have improved
      the efficacy and safety of ocularallergy treatment. This article discusses the
      classification of ocular allergy diagnosis and management, and addresses clinical
      symptoms and signs that indicate more severe allergic disease or alternative
      diagnosis that should prompt expeditious referral to an ophthalmologist. 

PMID- 24852157
TI  - Convergence insufficiency and vision therapy.
AB  - There is no standard meaning of the term "vision therapy", and for this reason it
      is often a controversial topic between some members of the ophthalmic and
      optometric community. Most pediatric ophthalmologists avoid using the term
      because it is nonspecific. Convergence Insufficiency (CI) is a binocular visual
      problem that causes problems and symptoms with near fixation. There is consensus
      among eye care professionals that convergence therapy is effective in treating
      CI. Convergence therapy is not effective in treating learning disabilities, but
      can sometimes relieve symptoms that might be a barrier to reading. 

PMID- 24852158
TI  - Pediatric Clinics of North America. Pediatric ophthalmology. Foreword.

PMID- 24852159
TI  - Pediatric Clinics of North America. Pediatric ophthalmology. Preface.

PMID- 24852160
TI  - Presidential Address: We Can Move Mountains, One Step at a Time.

PMID- 24852162
TI  - Introduction to the CPNP 2014 Poster Abstracts.

PMID- 24852164
TI  - A theoretical study on the reaction pathways and the mechanism of 1,3- dipolar
      cycloaddition of vinyl acetylene and methyl azide.
AB  - 1,3-dipolar cycloaddition procedure is one of the most widely practiced methods
      in order to synthesize heterocyclic compounds. Although, it seems very simple,
      but, there are numerous precursors of heterocyclic molecules who have more than
      one positions to react with a 1,3-dipole species. As a result, while using a
      precursor with more than one position for reaction, it is probable to synthesize
      several products with different structures. This paper studies all possible
      interactions of vinyl acetylene, which has two positions for reaction, with
      methyl azide. This reaction could lead to the emergence of any 1,3-dipolar
      cycloaddition products. Our ultimate goal is to help researchers to find out how
      precursors containing both carbon-carbon double, and the triple bonds interact
      with 1,3- dipolar species. The present study used the DFT calculations at B3LYP/6
      311++G(3df,pd) level to check all probable interactions between vinyl acetylene
      and methyl azide, and determined Potential Energy Surface, and optimized all
      species. 

PMID- 24852165
TI  - Ventilation/perfusion scintigraphy in children with post-infectious bronchiolitis
      obliterans: a pilot study.
AB  - PURPOSE: Childhood post-infectious bronchiolitis obliterans (BO) is an infrequent
      lung disease leading to narrowing and/or complete obliteration of small airways.
      Ventilation and perfusion (V/Q) scan can provide both regional and global
      pulmonary information. However, only few retrospective researches investigating
      post-infectious BO involved V/Q scan, the clinical value of this method is
      unknown. This preliminary prospective study was aimed to evaluate the correlation
      of V/Q scan with disease severity, pulmonary function test results, and prognosis
      in children with post-infectious BO. METHODS: Twenty-five post-infectious BO
      children (18 boys and 7 girls; mean age, 41 months) underwent V/Q scan and
      pulmonary function tests. Patients were followed after their inclusion.
      Ventilation index and perfusion index obtained from V/Q scan were used to measure
      pulmonary abnormalities. Spearman's rank correlation test of ventilation index
      and perfusion index on disease severity, lung function tests indices, and follow
      up results were performed. RESULTS: The median follow-up period was 4.6 years
      (range, 2.2 to 5.0 years). Ventilation index and perfusion index were both
      correlated with disease severity (r = 0.72, p<0.01 and r = 0.73, p<0.01), but
      only ventilation index was related to pulmonary function tests results (all
      p<0.05). In addition, Spearman test yielded significant correlations between
      perfusion index and prognosis (r = 0.77, p<0.01), and ventilation index and
      prognosis (r = 0.63, p = 0.01). CONCLUSIONS: For children with post-infectious
      BO, the present study preliminarily indicated that the degree of ventilation and
      perfusion abnormalities evaluated by V/Q scan may be used to assess disease
      severity, and may be predictive of patient's outcome.

PMID- 24852166
TI  - An improved model for nucleation-limited ice formation in living cells during
      freezing.
AB  - Ice formation in living cells is a lethal event during freezing and its
      characterization is important to the development of optimal protocols for not
      only cryopreservation but also cryotherapy applications. Although the model for
      probability of ice formation (PIF) in cells developed by Toner et al. has been
      widely used to predict nucleation-limited intracellular ice formation (IIF), our
      data of freezing Hela cells suggest that this model could give misleading
      prediction of PIF when the maximum PIF in cells during freezing is less than 1
      (PIF ranges from 0 to 1). We introduce a new model to overcome this problem by
      incorporating a critical cell volume to modify the Toner's original model. We
      further reveal that this critical cell volume is dependent on the mechanisms of
      ice nucleation in cells during freezing, i.e., surface-catalyzed nucleation (SCN)
      and volume-catalyzed nucleation (VCN). Taken together, the improved PIF model may
      be valuable for better understanding of the mechanisms of ice nucleation in cells
      during freezing and more accurate prediction of PIF for cryopreservation and
      cryotherapy applications. 

PMID- 24852167
TI  - Spatiotemporal lipid profiling during early embryo development of Xenopus laevis
      using dynamic ToF-SIMS imaging.
AB  - Time-of-flight secondary ion mass spectrometry (ToF-SIMS) imaging has been used
      for the direct analysis of single intact Xenopus laevis embryo surfaces, locating
      multiple lipids during fertilization and the early embryo development stages with
      subcellular lateral resolution (~4 MUm). The method avoids the complicated sample
      preparation for lipid analysis of the embryos, which requires selective chemical
      extraction of a pool of samples and chromatographic separation, while preserving
      the spatial distribution of biological species. The results show ToF-SIMS is
      capable of profiling multiple components (e.g., glycerophosphocholine, SM,
      cholesterol, vitamin E, diacylglycerol, and triacylglycerol) in a single X.
      laevis embryo. We observe lipid remodeling during fertilization and early embryo
      development via time course sampling. The study also reveals the lipid
      distribution on the gamete fusion site. The methodology used in the study opens
      the possibility of studying developmental biology using high resolution imaging
      MS and of understanding the functional role of the biological molecules. 

PMID- 24852169
TI  - An extremely simple method for fabricating 3D protein microarrays with an anti
      fouling background and high protein capacity.
AB  - Protein microarrays have become vital tools for various applications in
      biomedicine and bio-analysis during the past decade. The intense requirements for
      a lower detection limit and industrialization in this area have resulted in a
      persistent pursuit to fabricate protein microarrays with a low background and
      high signal intensity via simple methods. Here, we report on an extremely simple
      strategy to create three-dimensional (3D) protein microarrays with an anti
      fouling background and a high protein capacity by photo-induced surface
      sequential controlled/living graft polymerization developed in our lab. According
      to this strategy, "dormant" groups of isopropyl thioxanthone semipinacol (ITXSP)
      were first introduced to a polymeric substrate through ultraviolet (UV)-induced
      surface abstraction of hydrogen, followed by a coupling reaction. Under visible
      light irradiation, the ITXSP groups were photolyzed to initiate surface living
      graft polymerization of poly(ethylene glycol) methyl methacrylate (PEGMMA), thus
      introducing PEG brushes to the substrate to generate a full anti-fouling
      background. Due to the living nature of this graft polymerization, there were
      still ITXSP groups on the chain ends of the PEG brushes. Therefore, by in situ
      secondary living graft cross-linking copolymerization of glycidyl methacrylate
      (GMA) and polyethylene glycol diacrylate (PEGDA), we could finally plant height
      controllable cylinder microarrays of a 3D PEG network containing reactive epoxy
      groups onto the PEG brushes. Through a commonly used reaction of amine and epoxy
      groups, the proteins could readily be covalently immobilized onto the
      microarrays. This delicate design aims to overcome two universal limitations in
      protein microarrays: a full anti-fouling background can effectively eliminate
      noise caused by non-specific absorption and a 3D reactive network provides a
      larger protein-loading capacity to improve signal intensity. The results of non
      specific protein absorption tests demonstrated that the introduction of PEG
      brushes greatly improved the anti-fouling properties of the pristine low-density
      polyethylene (LDPE), for which the absorption to bovine serum albumin was reduced
      by 83.3%. Moreover, the 3D protein microarrays exhibited a higher protein
      capacity than the controls to which were attached the same protein on PGMA
      brushes and monolayer epoxy functional groups. The 3D protein microarrays were
      used to test the immunoglobulin G (IgG) concentration in human serum, suggesting
      that they could be used for biomedical diagnosis, which indicates that more
      potential bio-applications could be developed for these protein microarrays in
      the future. 

PMID- 24852168
TI  - Lipoprotein subclasses and endogenous sex hormones in women at midlife.
AB  - The objective of this work was to evaluate the associations between levels of
      endogenous sex hormones in women at midlife and lipoprotein subclasses. One
      hundred and twenty women (68 late peri-/postmenopausal and 52 pre-/early
      perimenopausal) from the Study of Women's Health Across the Nation (Pittsburgh
      site) were included. Lipoprotein subclasses were quantified using NMR
      spectroscopy. Participants (57.5% White and 42.5% Black) were 50.4 +/- 1.9 years
      old. Adjusting for age, race, cycle day of blood draw, BMI, physical activity,
      and alcohol consumption, a negative correlation was found between estradiol (E2)
      and medium-small LDL particle (LDL-P) concentration (rho = -0.19, P = 0.04).
      Further, E2 was positively correlated with HDL particle (HDL-P) size (rho = 0.22,
      P = 0.02). For sex hormone binding globulin (SHBG), independent negative
      correlation was found with total small LDL-P concentration. SHBG was also
      positively correlated with LDL-P and HDL-P sizes (P < 0.05 for all). For free
      androgen index (FAI), positive correlations were found with concentrations of
      total VLDL particles, total LDL-Ps, and total small LDL-Ps. Additionally, FAI was
      negatively correlated with large HDL-P concentration, and HDL-P and LDL-P sizes
      (P < 0.05 for all). Lower levels of E2 and SHBG, and higher levels of FAI were
      associated with a more atherogenic profile of lipoprotein subclasses. Sex hormone
      levels at midlife may increase women's risk of coronary heart disease.

PMID- 24852170
TI  - Octopamine neuromodulation regulates Gr32a-linked aggression and courtship
      pathways in Drosophila males.
AB  - Chemosensory pheromonal information regulates aggression and reproduction in many
      species, but how pheromonal signals are transduced to reliably produce behavior
      is not well understood. Here we demonstrate that the pheromonal signals detected
      by Gr32a-expressing chemosensory neurons to enhance male aggression are filtered
      through octopamine (OA, invertebrate equivalent of norepinephrine) neurons. Using
      behavioral assays, we find males lacking both octopamine and Gr32a gustatory
      receptors exhibit parallel delays in the onset of aggression and reductions in
      aggression. Physiological and anatomical experiments identify Gr32a to octopamine
      neuron synaptic and functional connections in the suboesophageal ganglion.
      Refining the Gr32a-expressing population indicates that mouth Gr32a neurons
      promote male aggression and form synaptic contacts with OA neurons. By
      restricting the monoamine neuron target population, we show that three previously
      identified OA-Fru(M) neurons involved in behavioral choice are among the Gr32a-OA
      connections. Our findings demonstrate that octopaminergic neuromodulatory neurons
      function as early as a second-order step in this chemosensory-driven male social
      behavior pathway.

PMID- 24852171
TI  - Broad-spectrum anti-biofilm peptide that targets a cellular stress response.
AB  - Bacteria form multicellular communities known as biofilms that cause two thirds
      of all infections and demonstrate a 10 to 1000 fold increase in adaptive
      resistance to conventional antibiotics. Currently, there are no approved drugs
      that specifically target bacterial biofilms. Here we identified a potent anti
      biofilm peptide 1018 that worked by blocking (p)ppGpp, an important signal in
      biofilm development. At concentrations that did not affect planktonic growth,
      peptide treatment completely prevented biofilm formation and led to the
      eradication of mature biofilms in representative strains of both Gram-negative
      and Gram-positive bacterial pathogens including Pseudomonas aeruginosa,
      Escherichia coli, Acinetobacter baumannii, Klebsiella pneumoniae, methicillin
      resistant Staphylococcus aureus, Salmonella Typhimurium and Burkholderia
      cenocepacia. Low levels of the peptide led to biofilm dispersal, while higher
      doses triggered biofilm cell death. We hypothesized that the peptide acted to
      inhibit a common stress response in target species, and that the stringent
      response, mediating (p)ppGpp synthesis through the enzymes RelA and SpoT, was
      targeted. Consistent with this, increasing (p)ppGpp synthesis by addition of
      serine hydroxamate or over-expression of relA led to reduced susceptibility to
      the peptide. Furthermore, relA and spoT mutations blocking production of (p)ppGpp
      replicated the effects of the peptide, leading to a reduction of biofilm
      formation in the four tested target species. Also, eliminating (p)ppGpp
      expression after two days of biofilm growth by removal of arabinose from a strain
      expressing relA behind an arabinose-inducible promoter, reciprocated the effect
      of peptide added at the same time, leading to loss of biofilm. NMR and
      chromatography studies showed that the peptide acted on cells to cause
      degradation of (p)ppGpp within 30 minutes, and in vitro directly interacted with
      ppGpp. We thus propose that 1018 targets (p)ppGpp and marks it for degradation in
      cells. Targeting (p)ppGpp represents a new approach against biofilm-related drug
      resistance. 

PMID- 24852172
TI  - No evidence for race and socioeconomic status as independent predictors of 30-day
      readmission rates following orthopedic surgery.
AB  - The Centers for Medicare & Medicaid Services considers readmissions within 30
      days of discharge to be a quality indicator. Hospitals' and eventually
      physicians' readmission rates will be used to determine payment for services. It
      is imperative that health care providers understand which patients are at risk
      for readmission so that they can apply the appropriate preventive interventions.
      The research team analyzed all orthopedic admissions and readmissions at their
      institution from September 2008 to April 2011 in this study. Preparing for the
      next stage in health care reform, identifying any preoperative factors that may
      place certain patients into a "high-risk" category for readmission following an
      orthopedic procedure is of paramount importance. This data analysis of more than
      13 000 patients noted that race-based and income-based risk factors did not
      translate into significant risk factors or predictors of 30-day readmission
      following orthopedic admission. 

PMID- 24852174
TI  - Multiple resistances and complex mechanisms of Anopheles sinensis mosquito: a
      major obstacle to mosquito-borne diseases control and elimination in China.
AB  - Malaria, dengue fever, and filariasis are three of the most common mosquito-borne
      diseases worldwide. Malaria and lymphatic filariasis can occur as concomitant
      human infections while also sharing common mosquito vectors. The overall
      prevalence and health significance of malaria and filariasis have made them top
      priorities for global elimination and control programmes. Pyrethroid resistance
      in anopheline mosquito vectors represents a highly significant problem to malaria
      control worldwide. Several methods have been proposed to mitigate insecticide
      resistance, including rotational use of insecticides with different modes of
      action. Anopheles sinensis, an important malaria and filariasis vector in
      Southeast Asia, represents an interesting mosquito species for examining the
      consequences of long-term insecticide rotation use on resistance. We examined
      insecticide resistance in two An. Sinensis populations from central and southern
      China against pyrethroids, organochlorines, organophosphates, and carbamates,
      which are the major classes of insecticides recommended for indoor residual
      spray. We found that the mosquito populations were highly resistant to the four
      classes of insecticides. High frequency of kdr mutation was revealed in the
      central population, whereas no kdr mutation was detected in the southern
      population. The frequency of G119S mutation in the ace-1 gene was moderate in
      both populations. The classification and regression trees (CART) statistical
      analysis found that metabolic detoxification was the most important resistance
      mechanism, whereas target site insensitivity of L1014 kdr mutation played a less
      important role. Our results indicate that metabolic detoxification was the
      dominant mechanism of resistance compared to target site insensitivity, and
      suggests that long-term rotational use of various insecticides has led An.
      sinensis to evolve a high insecticide resistance. This study highlights the
      complex network of mechanisms conferring multiple resistances to chemical
      insecticides in mosquito vectors and it has important implication for designing
      and implementing vector resistance management strategies. 

PMID- 24852173
TI  - Impact of light/dark cycle patterns on oxidative stress in an adriamycin-induced
      nephropathy model in rats.
AB  - The principal goal of this study was to determine the effect of the photoperiod
      on oxidative damage biomarkers in rats submitted to different light/darkness
      patterns, in a hyperlipidemic nephropathy model (induced by adriamycin), as well
      as its possible relationship with melatonin and leptin secretion rhythms. To test
      this hypothesis, six different groups were used (N = 6 rats per group): control
      (12 h/12h light:dark); exposure to permanent illumination (24 h light); exposure
      to darkness (22 h dark); injected with adriamycin, 12h/12h light:dark; injected
      with adriamycin + exposure to permanent illumination and injected with adriamycin
      + exposure to darkness (22 h dark). The different photoperiods were begun two
      weeks prior to medication and were maintained up to the day of the animal's
      sacrifice, ten days after medication. The following parameters were analysed: i)
      weight evolution; ii) in plasma: urea, creatinine, uric acid, total proteins,
      albumen, lactate dehydrogenase, creatinine-quinase, aspartate aminotransferase,
      alanine aminotransferase and total cholesterol; iii) in urine: urea, creatinine,
      total proteins and microalbumen; iv) biomarkers of oxidative damage in kidneys,
      heart, liver and brain: lipoperoxides, total glutathione, reduced glutathione,
      catalase, glutathione peroxidase, glutathione reductase and glutathione
      transferase; v) melatonin (pineal gland tissue and plasma) and leptin (plasma).
      From the results obtained it was concluded that the administration of adriamycin
      generated oxidative stress in renal, cerebral, hepatic and cardiac tissue.
      Additionally, in the healthy animal, but of a lesser relevance in the adriamycin
      animal, permanent light worsened the oxidative stress, whereas darkness improved
      it. This could be related to the circadian rhythm of the inverse release shown by
      melatonin and leptin, accentuating the release of melatonin in the darkness phase
      and that of leptin in the light phase. The correlation between melatonin and
      leptin in the healthy animal seemed to confirm the relationship between both
      variables and their influence on oxidative damage biomarkers. 

PMID- 24852175
TI  - Taximin, a conserved plant-specific peptide is involved in the modulation of
      plant-specialized metabolism.
AB  - Small peptides play important roles in the signalling cascades that steer plant
      growth, development and defence, and often crosstalk with hormonal signalling.
      Thereby, they also modulate metabolism, including the production of bioactive
      molecules that are of high interest for human applications. Yew species (Taxus
      spp.) produce diterpenes such as the powerful anticancer agent paclitaxel, the
      biosynthesis of which can be stimulated by the hormone jasmonate, both in whole
      plants and cell suspension cultures. Here, we identified Taximin, as a gene
      encoding a hitherto unreported, plant-specific, small, cysteine-rich signalling
      peptide, through a transcriptome survey of jasmonate-elicited T. baccata
      suspension cells grown in two-media cultures. Taximin expression increased in a
      coordinated manner with that of paclitaxel biosynthesis genes. Tagged Taximin
      peptides were shown to enter the secretory system and localize to the plasma
      membrane. In agreement with this, the exogenous application of synthetic Taximin
      peptide variants could transiently modulate the biosynthesis of taxanes in T.
      baccata cell suspension cultures. Importantly, the Taximin peptide is widely
      conserved in the higher plant kingdom with a high degree of sequence
      conservation. Accordingly, Taximin overexpression could stimulate the production
      of nicotinic alkaloids in Nicotiana tabacum hairy root cultures in a synergistic
      manner with jasmonates. In contrast, no pronounced effects of Taximin
      overexpression on the specialized metabolism in Medicago truncatula roots were
      observed. This study increases our understanding of the regulation of Taxus
      diterpene biosynthesis in particular and plant metabolism in general. Ultimately,
      Taximin might increase the practical potential of metabolic engineering of
      medicinal plants. 

PMID- 24852176
TI  - Hypertension in postmenopausal women: how to approach hypertension in menopause.
AB  - During fertile life women are usually normo or hypotensive. Hypertension may
      appear during pregnancy and this represents a peculiar phenomenon increasing
      nowadays for delay time of pregnancy. Gestational hypertension appears partially
      similar to hypertension in the context of metabolic syndrome for a similar
      condition of increased waste circumference. Parity, for the same pathogenesis,
      has been reported to be associated to peri and postmenopausal hypertension, not
      confirmed by our study of parous women with transitional non persistent
      perimenopausal hypertension. Estrogen's deficiency inducing endothelial
      dysfunction and increased body mass index are the main cause for hypertension in
      this phase of life. For these reasons lifestyle modification, diet and
      endothelial active drugs represent the ideal treatment. Antioxidant agents may
      have a role in prevention and treatment of hypertension. In conclusion,
      hypertension in women represents a peculiar constellation of different biological
      and pathogenic factors, which need a specific gender related approach,
      independent from the male model. 

PMID- 24852177
TI  - BioCreative-IV virtual issue.

PMID- 24852178
TI  - Survey on the current trends in managing intrauterine growth restriction.
AB  - OBJECTIVE: To provide a snapshot of the current trends in managing intrauterine
      growth restriction (IUGR) and to assess the agreement on the gestational age and
      the way of delivery in different clinical scenarios. METHODS: A PubMed search was
      performed to identify all original articles on IUGR in the last 6 years. The most
      active 20 authors were selected as experts and were invited to respond to a
      survey on their preferred gestational age for elective delivery in several IUGR
      cases depending on Doppler measurements (including umbilical artery (UA), middle
      cerebral artery, cerebroplacental ratio, uterine artery and ductus venosus),
      biophysical profile and cardiotocography. RESULTS: 15 of the 20 selected experts
      agreed to participate in the survey, of which 3 failed to meet the deadline to
      complete the survey. Management of IUGR was relatively uniform for abnormal UA,
      uterine artery or cerebroplacental ratio. Although average gestational age at
      delivery reflected a clear progression with accepted markers of severity,
      discrepancies of up to 4 weeks were found for abnormal middle cerebral artery
      Doppler and absent end-diastolic velocity in the UA, and of up to 8 weeks for
      reverse end-diastolic velocity in the UA and abnormalities in the ductus venosus
      Doppler. CONCLUSIONS: Management of IUGR is still far from being uniform among
      centers, with most controversy surrounding the management of early-onset IUGR.
      There is a need of prospective studies to address this issue.

PMID- 24852179
TI  - Impact of physical activity interventions on anthropometric outcomes: systematic
      review and meta-analysis.
AB  - Considerable research has tested physical activity (PA) interventions to prevent
      and treat overweight and obesity. This comprehensive meta-analysis synthesized
      the anthropometric effects of supervised exercise interventions and motivational
      interventions to increase PA. Eligible intervention studies included healthy
      participants with reported anthropometric outcomes [e.g., body mass index (BMI)].
      Extensive searching located 54,642 potentially eligible studies. We included data
      from 535 supervised exercise and 283 motivational interventions in our syntheses,
      which used random-effects analyses. Exploratory moderator analyses used meta
      analytic analogues of ANOVA and regression. We synthesized data from 20,494
      participants in supervised exercise and 94,711 undergoing motivational
      interventions. The overall mean effect sizes (ES, d) for treatment versus control
      groups in supervised exercise interventions were 0.20 (treatment vs. control
      within-group comparison) and 0.22 (between-group comparison). The ES of 0.22
      represents a post-intervention BMI of 26.7 kg/m(2) for treatment participants
      relative to 27.7 kg/m(2) for controls. The corresponding mean ES for motivational
      interventions was significantly smaller (d = 0.09 for between group, d = 0.10 for
      treatment vs. control within-group). Control group within-group comparisons
      revealed slightly worsening anthropometric outcomes during study participation (d
      = -0.03 to -0.04). Moderator analyses identified potential variables for future
      research. These findings document significant improvements in anthropometric
      effects from both supervised exercise and motivational interventions.

PMID- 24852180
TI  - Drug-eluting stent, but not bare metal stent, accentuates the systematic
      inflammatory response in patients.
AB  - OBJECTIVE: The systematic pro-inflammatory responses after percutaneous coronary
      intervention with drug-eluting stents (DES) remain poorly defined. Therefore, we
      compared the systematic pro-inflammatory state of circulating mononuclear cells
      (MNCs) between DES and bare metal stent (BMS) implantation. METHODS: Patients
      with indications for treatment with stents were randomized in a 1:1 ratio to
      placement of DES or BMS. The primary endpoint was a change of pro-inflammatory
      state at 12 weeks post-procedure. RESULTS: Thirty-six consecutive patients
      received DES or BMS. At 12 weeks after stent implantation, the lipid profile and
      high-sensitivity C-reactive protein (hs-CRP) improved significantly in both
      groups. The mRNA levels and plasma concentrations of interleukin-6, tumor
      necrosis factor-alpha and matrix metalloproteinase-9 were significantly elevated
      in the DES group, which was not observed in the BMS group. An increase in NF
      kappaB binding activity and a decrease in PPAR-gamma expression in MNCs were
      observed in the DES group, along with increases in IkappaB phosphorylation and
      p50 expression. However, similar changes were not observed in the BMS group.
      CONCLUSIONS: Systematic inflammatory responses were accentuated after the
      patients were treated percutaneously with DES, despite their improved lipid
      profile and hs-CRP. These data may provide fundamental information for optimizing
      therapeutic strategy in the era of DES.

PMID- 24852182
TI  - Geographic variation in out-of-pocket expenditures of elderly Medicare
      beneficiaries.
AB  - OBJECTIVES: To examine whether out-of-pocket expenditures (OOPEs) exhibit the
      same geographic variation as Medicare claims, given wide variation in the costs
      of U.S. health care, but no information on how that translates into OOPEs or
      financial burden for older Americans. DESIGN: Retrospective cohort study.
      SETTING: Data from the Health and Retirement Study linked to Medicare claims.
      PARTICIPANTS: A nationally representative cohort of 4,657 noninstitutionalized,
      community-dwelling, fee-for-service elderly Medicare beneficiaries interviewed in
      2006 and 2008. MEASUREMENTS: The primary predictor was per capita Medicare
      spending quintile according to hospital referral region. The primary outcome was
      a self-reported, validated measure of annual OOPEs excluding premiums. RESULTS:
      Mean and median adjusted per capita Medicare payments were $5,916 and $2,635,
      respectively; mean and median adjusted OOPEs were $1,525 and $779, respectively.
      Adjusted median Medicare payments were $3,474 in the highest cost quintile and
      $1,942 in the lowest cost quintile (ratio 1.79, P < .001 for difference). In
      contrast, adjusted median OOPEs were not higher in the highest than in the lowest
      Medicare cost quintile ($795 vs $764 for a Q5:Q1 ratio of 1.04, P = .42). The
      Q5:Q1 ratio was 1.48 for adjusted mean Medicare payments and 1.04 for adjusted
      mean OOPEs (both P < .001). CONCLUSION: Medicare payments vary widely between
      high- and low-cost regions, but OOPEs do not.

PMID- 24852183
TI  - Owl monkeys (Aotus spp.) perform self- and social anointing in captivity.
AB  - Several species of primates, including owl monkeys (Aotus spp.), anoint by
      rubbing their fur with odiferous substances. Previous research has shown that
      capuchin monkeys (Cebus and Sapajus) anoint socially by rubbing their bodies
      together in groups of two or more while anointing. Owl monkeys housed at the
      DuMond Conservancy have been observed to anoint over the last 10 years, and we
      report detailed new information on the anointing behavior of this population,
      including descriptions of social anointing which occurs frequently. We first
      investigated the occurrence of self-anointing in 35 Aotus spp. presented with
      millipedes. Detailed descriptions regarding body regions anointed were obtained
      for all anointers (n = 28). The median duration for a self-anointing bout was 3.6
      min (range from approx. 2 s to 14.15 min). While the latency and length of
      anointing bouts showed considerable interindividual differences, no statistically
      significant differences were found between sexes, wild- or captive-born owl
      monkeys or across age groups. However, we found the lower back and tail were
      anointed at a rate significantly greater than other body parts, but there were no
      differences in these patterns across sex or wild- or captive-born owl monkeys.
      More recently, social anointing was investigated in 26 Aotus spp. presented with
      millipedes, of which half were observed to anoint socially. The average duration
      for all social anointing bouts was 72.88 s, with a median duration of 30 s (range
      5-322 s). A detailed ethogram was also generated that included behaviors that
      were performed while anointing, including facial expressions and vocalizations.
      The intraindividual variability for 8 monkeys used in both investigations is
      discussed. These findings extend our knowledge of anointing and confirm the
      existence of social anointing in another genus with a unique biology (nocturnal
      and socially monogamous) distinct from capuchins.

PMID- 24852181
TI  - Oncogenic drivers, targeted therapies, and acquired resistance in non-small-cell
      lung cancer.
AB  - In the past decade, a shift toward targeted therapies in non-small-cell lung
      cancer following molecular profiling has dramatically changed the way advanced
      adenocarcinoma is treated. However, tumor cells inevitably acquire resistance to
      such therapies, circumventing any sustained clinical benefit. As the genomic
      classification of lung cancer continues to evolve and as the mechanisms of
      acquired resistance to targeted therapies become elucidated and more improved
      target-specific drugs come into sight, the future will see more promising results
      from the clinic through the development of new therapeutic strategies to
      overcome, or prevent the development of, resistance for lung cancer patients. 

PMID- 24852184
TI  - Enhancing dissemination and implementation research using systems science
      methods.
AB  - BACKGROUND: Dissemination and implementation (D&I) research seeks to understand
      and overcome barriers to adoption of behavioral interventions that address
      complex problems, specifically interventions that arise from multiple interacting
      influences crossing socio-ecological levels. It is often difficult for research
      to accurately represent and address the complexities of the real world, and
      traditional methodological approaches are generally inadequate for this task.
      Systems science methods, expressly designed to study complex systems, can be
      effectively employed for an improved understanding about dissemination and
      implementation of evidence-based interventions. PURPOSE: The aims of this study
      were to understand the complex factors influencing successful D&I of programs in
      community settings and to identify D&I challenges imposed by system complexity.
      METHOD: Case examples of three systems science methods-system dynamics modeling,
      agent-based modeling, and network analysis-are used to illustrate how each method
      can be used to address D&I challenges. RESULTS: The case studies feature relevant
      behavioral topical areas: chronic disease prevention, community violence
      prevention, and educational intervention. To emphasize consistency with D&I
      priorities, the discussion of the value of each method is framed around the
      elements of the established Reach Effectiveness Adoption Implementation
      Maintenance (RE-AIM) framework. CONCLUSION: Systems science methods can help
      researchers, public health decision makers, and program implementers to
      understand the complex factors influencing successful D&I of programs in
      community settings and to identify D&I challenges imposed by system complexity.

PMID- 24852185
TI  - Structural and energetic properties of acetonitrile-Group IV (A & B) halide
      complexes.
AB  - We have conducted an extensive computational study of the structural and
      energetic properties of select acetonitrile-Group IV (A & B) tetrahalide
      complexes, both CH3CN-MX4 and (CH3CN)2-MX4 (M = Si, Ge, Ti; X = F, Cl). We have
      also examined the reactivity of CH3CN with SiF4, SiCl4, GeCl4, and TiCl4, and
      measured low-temperature IR spectra of thin films containing CH3CN with SiF4,
      GeCl4, or TiCl4. The six 1:1 complexes fall into two general structural classes.
      CH3CN-TiCl4, CH3CN-TiF4, and CH3CN-GeF4, exhibit relatively short M-N bonds (~2.3
      A), an intermediate degree of distortion in the MX4 subunit, and binding energies
      ranging from 11.0 to 13.0 kcal/mol. Conversely, CH3CN-GeCl4, CH3CN-SiF4, and
      CH3CN-SiCl4, are weakly bonded systems, with long M-N distances (>3.0 A), little
      distortion in the MX4 subunit, and binding energies ranging from 3.0 to 4.4
      kcal/mol. The structural features of analogous 2:1 systems resemble those of
      their 1:1 counterparts, whereas the binding energies (relative to three isolated
      fragments) are roughly twice as large. Calculated M-N potential curves in the gas
      phase and bulk, dielectric media are reported for all 1:1 complexes, and for two
      systems, CH3CN-GeF4 and CH3CN-SiF4, these data predict significant condensed
      phase structural changes. The effect on the CH3CN-SiF4 potential is extreme; the
      curve becomes quite flat over a broad range in dielectric media, and at higher
      epsilon values, the global minimum shifts inward by about 1.0 A. In bulk
      reactivity experiments, no reaction was observed between CH3CN and SiF4, SiCl4,
      or GeCl4, whereas CH3CN and TiCl4 were found to react immediately upon contact.
      Also, thin-film IR spectra indicate a strong interaction between CH3CN and TiCl4,
      yet only weak interactions between CH3CN and GeCl4 or SiF4 in the solid state.

PMID- 24852186
TI  - Intergenic lncRNAs and the evolution of gene expression.
AB  - Eukaryote genomes encode a surprisingly large number of noncoding transcripts.
      Around two-thirds of human transcribed loci do not encode protein, and many are
      intergenic and produce long (>200 nucleotides) noncoding RNAs (lncRNAs).
      Extensive analyses using comparative genomics and transcriptomics approaches have
      established that lncRNA sequence and transcription tend to turn over rapidly
      during evolution. Our appreciation of the biological roles of lncRNAs, based only
      on a handful of transcripts with well-characterized functions, is that lncRNAs
      have diverse roles in regulating gene expression. These proposed roles together
      with their rapid rates of evolution suggest that lncRNAs could contribute to the
      divergent expression patterns observed among species and potentially to the
      origin of new traits. 

PMID- 24852187
TI  - Value of 18F-FDG uptake on PET/CT and CEA level to predict epidermal growth
      factor receptor mutations in pulmonary adenocarcinoma.
AB  - PURPOSE: The identification of the mutation status of the epidermal growth factor
      receptor (EGFR) is important for the optimization of treatment in patients with
      pulmonary adenocarcinoma. The acquisition of adequate tissues for EGFR mutational
      analysis is sometimes not feasible, especially in advanced-stage patients. The
      aim of this study was to predict EGFR mutation status in patients with pulmonary
      adenocarcinoma based on (18)F-fluorodeoxyglucose (FDG) uptake and imaging
      features in positron emission tomography/computed tomography (PET/CT), as well as
      on the serum carcinoembryonic antigen (CEA) level. METHODS: We retrospectively
      reviewed 132 pulmonary adenocarcinoma patients who underwent EGFR mutation
      testing, pretreatment FDG PET/CT and serum CEA analysis. The associations between
      EGFR mutations and patient characteristics, maximal standard uptake value
      (SUVmax) of primary tumors, serum CEA level and CT imaging features were
      analyzed. Receiver-operating characteristic (ROC) curve analysis was performed to
      quantify the predictive value of these factors. RESULTS: EGFR mutations were
      identified in 69 patients (52.2 %). Patients with SUVmax >=6 (p = 0.002) and CEA
      level >=5 (p = 0.013) were more likely to have EGFR mutations. The CT
      characteristics of larger tumors (>=3 cm) (p = 0.023) and tumors with a
      nonspiculated margin (p = 0.026) were also associated with EGFR mutations.
      Multivariate analysis showed that higher SUVmax and CEA level, never smoking and
      a nonspiculated tumor margin were the most significant predictors of EGFR
      mutation. The combined use of these four criteria yielded a higher area under the
      ROC curve (0.82), suggesting a good discrimination. CONCLUSION: The combined
      evaluation of FDG uptake, CEA level, smoking status and tumor margins may be
      helpful in predicting EGFR mutation status in patients with pulmonary
      adenocarcinoma, especially when the tumor sample is inadequate for genetic
      analysis or genetic testing is not available. Further large-scale prospective
      studies are needed to validate these results.

PMID- 24852188
TI  - The role of metabolic tumor volume and total lesion glycolysis on 18F-FDG PET/CT
      in the prognosis of epithelial ovarian cancer.
AB  - PURPOSE: This study assessed the prognostic value of pre-operative 2-[(18)F]
      fluoro-2-deoxy-D-glucose ((18)F-FDG) positron emission tomography/computed
      tomography (PET/CT) volumetric parameters, including metabolic tumor volume (MTV)
      and total lesion glycolysis (TLG), in patients with epithelial ovarian cancer.
      METHODS: A total of 175 patients with epithelial ovarian cancer who underwent
      (18) F-FDG PET/CT and subsequent cytoreductive surgery were retrospectively
      enrolled. Maximum standardized uptake value (SUVmax) on (18)F-FDG PET/CT was
      measured for all patients. Because nine patients showed low tumor-to-background
      uptake ratios, MTV and TLG were measured in 166 patients. Univariate and
      multivariate analyses were performed to evaluate the prognostic significance of
      SUVmax, MTV, TLG, and clinicopathological factors for disease progression-free
      survival. RESULTS: Disease progressed in 78 (44.6 %) of the 175 patients, and the
      2-year disease progression-free survival rate was 57.5 %. Univariate analysis
      showed that tumor stage, histopathological type, presence of regional lymph node
      metastasis, residual tumor after cytoreductive surgery, pre-operative serum
      carbohydrate antigen 125 (CA125) level, SUVmax, MTV, and TLG were significant
      prognostic factors (p < 0.05). Among these variables, tumor stage (p = 0.0006)
      and TLG (p = 0.008) independently correlated with disease progression-free
      survival on multivariate analysis. The disease progression rate was only 2.3 % in
      stage I-II patients with low TLG (<=100.0), compared to 80.0 % in stage III-IV
      patients with high TLG (>100.0). CONCLUSION: Along with tumor stage, TLG is an
      independent prognostic factor for disease progression after cytoreductive surgery
      in patients with epithelial ovarian cancer. By combining tumor stage and TLG, one
      can further stratify the risk of disease progression for patients undergoing
      cytoreductive surgery.

PMID- 24852189
TI  - Halogen bonding of electrophilic bromocarbons with pseudohalide anions.
AB  - UV-Vis measurements showed that the interaction of pseudohalide anions, A(-) (A(
      ) = N3(-), NCO(-), NCS(-)), with electrophilic bromocarbons, R-Br (R-Br = CBr4,
      CBr3NO2, CBr3CONH2, CBr3H, CBr3F, CBr3CN or C3Br2F6), in solution results in
      formation of [R-Br, A(-)] complexes. These associates are characterized by
      intense absorption bands in the 200-350 nm range showing distinct Mulliken
      correlation with the frontier (HOMO-LUMO) orbitals' separations of the
      interacting anion and the R-Br electrophile. X-ray crystallographic studies
      established the principal structural features of the halogen-bonded associates
      between bromocarbons and polydentate pseudohalide anions. Specifically, in the
      (Pr4N)NCO.CBr4, (Pr4N)N3.CBr4 and (Pr4N)NCO.CBr3NO2 co-crystals, bromine
      substituents of the electrophiles are halogen-bonded with the (C=N or N=N) pi
      bonds of the cyanate or azide anions. Co-crystals of CBr4 with (Pr4N)NCS show two
      modes (C-Br...S-C and C-Br...N=C) of halogen bonding, while tribromoacetamide
      molecules form C-Br...S-C halogen bonds and N-H...N=C hydrogen bonds with
      thiocyanate anions. Structures and energetics of the halogen-bonded complexes
      resulted from the M06-2X/6-311+G(dp) computations of various R-Br-A(-) pairs were
      consistent with the experimental data. These computations revealed that the
      variations of the intramolecular (C-Br) and intermolecular (Br...A(-)) bond
      lengths are correlated with the A(-) -> R-Br charge transfer determined from
      Natural Bond Orbital analysis. Also, the scrutiny of the structural data
      indicated that the locations of the intermolecular contacts in these associates
      are determined primarily by the frontier orbital shapes of the halogen-bonded
      species. Thus, spectral and structural data point out a significant role of
      molecular-orbital (charge-transfer) interactions in formation of halogen bonded
      complexes involving pseudohalides and bromocarbons.

PMID- 24852190
TI  - Human herpesvirus 6 encephalitis simulating brain metastases in a patient with
      advanced small-cell lung cancer.
AB  - BACKGROUND: The brain is a frequent site of metastases in small-cell lung cancer.
      Symptoms of cerebral involvement are headache, disorientation, nausea/vomiting
      and seizures. CASE: A man with small-cell lung cancer developed a human
      herpesvirus 6 (HHV-6) meningoencephalitis with neurological symptoms that
      simulated brain involvement from the lung cancer. HHV-6 is a T cell lymphotropic
      virus which may be pathogenic in the immunocompromised host. HHV-6 remains latent
      after the first infection, and when the immune system is compromised it can
      reactivate. The treatment of HHV-6 infection is highly specific and the drugs
      recommended are the two antivirals, ganciclovir or foscarnet. CONCLUSION: In
      cancer patients neurologic symptoms are usually due to brain metastases. This
      case shows that in a cancer patient any aspecific neurologic symptom should be
      carefully evaluated in order to exclude a non-oncologic cause. This statement is
      particularly true if the therapies for the oncological and neurological diseases
      are effective.

PMID- 24852194
TI  - Comparative proteome analysis of peripheral neutrophils from sulfur mustard
      exposed and COPD patients.
AB  - Respiratory disorders in sulfur mustard (SM)-exposed and chronic obstructive
      pulmonary disease (COPD) patients are mostly associated with neutrophilic
      inflammation, severe airflow limitation, and oxidative stress. The objective of
      this study was to establish whether neutrophil (PMN) proteomes in these diseases
      were similar or differed. Blood neutrophil proteomes from healthy, SM-exposed,
      and COPD subjects were analyzed using two-dimensional gel electrophoresis
      followed by matrix-assisted laser desorption ionization time-of-flight mass
      spectrometry (MALDI TOF MS). Elastase activity was determined kinetically. The
      results showed that levels of S100 calcium-binding protein (CBP) A12, S100 CBP
      A8, glyceraldehyde-3-phosphate dehy-drogenase, superoxide dismutase, and protein
      disulfide isomerase proteins - as well as elastase activity - were significantly
      increased in PMN from 'diseased' hosts compared to in cells from healthy
      controls. In contrast, coactosin-like protein, RhoGDP dissociation inhibitor, and
      actin isoforms were significantly decreased in diseased subjects' PMN compared to
      PMN of healthy controls. Moreover, serpin B1 and coronin-1A were expressed only
      in PMN of the healthy subjects. Lastly, S100 CBP A9, endoplasmic reticulum (ER)
      60 protease, and glutathione-S-transferase isoforms were differentially expressed
      in the cells from the SM-exposed and COPD subjects. These results show that
      serpin B1, an efficient inhibitor of neutrophil serine proteases, was not
      detectable, and elastase activity significantly increased in PMN from both SM
      exposed and COPD patients. It seems that, apart from inflammation and oxidative
      stress, a protease:anti-protease imbalance exists within PMN of both COPD and SM
      exposed patients.

PMID- 24852195
TI  - Re: Biochemical evaluation of immunotoxic effects of cadmium in rats.

PMID- 24852197
TI  - Comparison of anterior segment measurements with optical low-coherence
      reflectometry and rotating dual Scheimpflug analysis.
AB  - PURPOSE: To compare the anterior segment measurements obtained with optical low
      coherence reflectometry (OLCR) (Lenstar LS 900, version 2.1.1) and rotating dual
      Scheimpflug analysis (Galilei G1, version 3). SETTING: Private practice,
      Policlinic Lleida, Lleida, Spain. DESIGN: Prospective comparative observational
      study. METHODS: The following measurements were performed in patients requiring a
      preoperative study for a refractive procedure or cataract surgery and healthy
      volunteers from the clinic's staff: central corneal thickness (CCT), anterior
      chamber depth (ACD), horizontal limbal distance (white-to-white distance [WTW]),
      pupil diameter, keratometry (K) readings at the steepest meridian (steep K) and
      the flattest meridian (flat K), corneal astigmatism power, and plus astigmatic
      cylinder. Measurements were taken using the OLCR device and rotating dual
      Scheimpflug analyzer. The main outcome measure was the degree of agreement
      between steep K, flat K, astigmatism power, cylinder axis, CCT, ACD, WTW, and
      pupil diameter measurements. RESULTS: The study enrolled 100 eyes of 100
      subjects. Steep K, flat K, corneal astigmatism power, cylinder axis, and WTW
      measurements with the OLCR device and Scheimpflug analyzer showed narrow 95%
      limits of agreement (LoA), which implies good agreement (P>.05, Bland-Altman plot
      analysis). In contrast, the range and 95% LoA for CCT, ACD, and pupil diameter
      values were statistically significantly different (P<.05, Bland-Altman plot
      analysis). CONCLUSION: In clinical practice, the OLCR device and the rotating
      dual Scheimpflug analyzer system can be used interchangeably for WTW measurements
      and K readings but not for CCT, ACD, and pupil diameter values. FINANCIAL
      DISCLOSURE: No author has a financial or proprietary interest in any material or
      method mentioned.

PMID- 24852198
TI  - Design and development of novel mitochondrial targeted nanocarriers, DQAsomes for
      curcumin inhalation.
AB  - Curcumin has potent antioxidant and anti-inflammatory properties but poor
      absorption following oral administration owing to its low aqueous solubility.
      Development of novel formulations to improve its in vivo efficacy is therefore
      challenging. In this study, formulation of curcumin-loaded DQAsomes (vesicles
      formed from the amphiphile, dequalinium) for pulmonary delivery is presented for
      the first time. The vesicles demonstrated mean hydrodynamic diameters between 170
      and 200 nm, with a zeta potential of approximately +50 mV, high drug loading (up
      to 61%) and encapsulation efficiency (90%), resulting in enhanced curcumin
      aqueous solubility. Curcumin encapsulation in DQAsomes in the amorphous state was
      confirmed by X-ray diffraction and differential scanning calorimetry analysis.
      The existence of hydrogen bonds and cation-pi interaction between curcumin and
      vesicle building blocks, namely dequalinium molecules, were shown in lyophilized
      DQAsomes using FT-IR analysis. Encapsulation of curcumin in DQAsomes enhanced the
      antioxidant activity of curcumin compared to free curcumin. DQAsome dispersion
      was successfully nebulized with the majority of the delivered dose deposited in
      the second stage of the twin-stage impinger. The vesicles showed potential for
      mitochondrial targeting. Curcumin-loaded DQAsomes thus represent a promising
      inhalation formulation with improved stability characteristics and mitochondrial
      targeting ability, indicating a novel approach for efficient curcumin delivery
      for effective treatment of acute lung injury and the rationale for future in vivo
      studies. 

PMID- 24852199
TI  - Pitfalls of ophthalmic radiographic imaging.
AB  - PURPOSE OF REVIEW: Ophthalmologists are dependent on computed tomography (CT) and
      MRI to aid in the diagnosis and management of patients with orbital and visual
      conditions. Pitfalls in the imaging process can lead to inefficient care or
      patient harm. This review summarizes these problems and provides methods to
      reduce imaging errors. RECENT FINDINGS: There has been exponential growth in the
      number of radiographic scans performed, resulting in increased awareness of the
      risks from medical radiation. Strategies to minimize radiation exposure include
      reducing the need for sequential scans, using appropriate technology, and
      substituting MRI for CT. Contrast administration can be associated with systemic
      reactions, renal disease, and thyroid dysfunction. Scan interpretation errors are
      reduced by the ophthalmologist reviewing the study and communication with the
      radiologist. SUMMARY: Medical radiation exposure can be reduced by initially
      ordering the appropriate scan and substituting MRI for CT when possible. MRI is
      contraindicated in patients with certain implants and metallic foreign bodies.
      Noncontrast studies are adequate to evaluate many conditions and some patients
      should not receive contrast. Imaging errors can be reduced by the ophthalmologist
      personally reviewing the orbital scans and correlating the results with the
      clinical findings.

PMID- 24852200
TI  - Update on Asian eyelid anatomy and clinical relevance.
AB  - PURPOSE OF REVIEW: Asians make up the world's largest ethnic group, and the
      eyelid is one of the most prominent features of the face, regardless of race.
      Recent advances in Asian eyelid research have improved the understanding of its
      unique anatomy and, more importantly, highlighted differences surgeons should be
      aware of when performing Asian eyelid surgery. RECENT FINDINGS: The most obvious
      characteristic of the Asian eyelid is the absent or very low lid crease and
      fuller upper eyelid. Caucasian eyelids typically have a double eyelid, but Asian
      eyelids can be categorized into three types: single eyelid, low eyelid crease,
      and double eyelid. Morphological variations in each layer from the different skin
      complexities to a taller, more circular-shaped orbital bone create a different
      eyelid appearance. Some components such as a submuscularis fibroadipose tissue
      layer and a lower-positioned transverse ligament were recently identified and
      found exclusively in the Asian eye. Many eyelid crease formation theories have
      been postulated, but none is scientifically proven because multiple factors are
      possibly involved. SUMMARY: Thorough understanding of Asian eyelid anatomy is
      imperative. The eyelid is the key distinctive feature of the Asian eye. Improving
      patient appearance while maintaining ethnic characteristics is the goal of Asian
      eyelid surgery.

PMID- 24852201
TI  - Spectrum of pediatric cancers in Mozambique: an analysis of hospital and
      population-based data.
AB  - The existing data provide little detail about the epidemiology of pediatric
      cancers in Mozambique. We aimed at characterizing the spectrum of pediatric
      cancers (0-14 years) diagnosed in Mozambique in two different calendar periods.
      Data were obtained from the Pathology Department of the Maputo Central Hospital
      (DP-HCM) (1999-2000 and 2009-2010), which receives virtually all samples for
      histopathological diagnosis in Maputo, with the exception of leukemia, and from
      the population-based Cancer Registry of Beira (2009-2010). In 1999-2000, the DP
      HCM diagnosed 61 cancers. Burkitt lymphoma, malignant bone tumors, and
      rhabdomyosarcomas accounted for 24.6%, 11.5%, and 9.8% of all cases,
      respectively. In 2009-2010, the number of cancers increased to 150, reflecting a
      two- to threefold increase in the proportion of Kaposi sarcomas, non-Hodgkin
      lymphomas, nephroblastomas, and neuroblastomas. In 2009-2010, the Cancer Registry
      of Beira registered 34 cases, corresponding to an incidence rate of 9.7/100,000
      inhabitants in this age group; Kaposi sarcomas, lymphomas, retinoblastomas, and
      nephroblastomas accounted for 29.4%, 23.5%, 8.8%, and 8.8% of all cases,
      respectively. These data show that pediatric cancers account for an appreciable
      burden in Mozambique, probably reflecting a high frequency of HIV-associated
      cancers and improved access to diagnosis, and highlight the potential for
      improving surveillance in this low resource setting.

PMID- 24852202
TI  - Traditional food patterns are associated with better diet quality and improved
      dietary adequacy in Aboriginal peoples in the Northwest Territories, Canada.
AB  - BACKGROUND: Traditionally, the Arctic diet has been derived entirely from locally
      harvested animal and plant species; however, in recent decades, imported foods
      purchased from grocery stores have become widely available. The present study
      aimed to examine Inuvialuit, traditional or nontraditional dietary patterns;
      nutrient density of the diet; dietary adequacy; and main food sources of energy
      and selected nutrient intakes. METHODS: This cross-sectional study used a
      culturally appropriate quantitative food frequency questionnaire to assess diet.
      Traditional and nontraditional eaters were classified as those consuming more or
      less than 300 g of traditional food daily. Nutrient densities per 4184 kJ (1000
      kcal) were determined. Dietary adequacy was determined by comparing participants'
      nutrient intakes with the Dietary Reference Intakes. RESULTS: The diet of
      nontraditional eaters contained, on average, a lower density of protein, niacin,
      vitamin B12 , iron, selenium, zinc, omega-3 fatty acids (P <= 0.0001), vitamin B6
      , potassium, thiamin, pantothenic acid (P <= 0.001), riboflavin and magnesium (P
      <= 0.05). Inadequate nutrient intake was more common among nontraditional eaters
      for calcium, folate, vitamin C, zinc, thiamin, pantothenic acid, vitamin K,
      magnesium, potassium and sodium. Non-nutrient-dense foods (i.e. high fat and high
      sugar foods) contributed to energy intake in both groups, more so among
      nontraditional eaters (45% versus 33%). Traditional foods accounted for 3.3% and
      20.7% of total energy intake among nontraditional and traditional eaters,
      respectively. CONCLUSIONS: Diet quality and dietary adequacy were better among
      Inuvialuit who consumed more traditional foods. The promotion of traditional
      foods should be incorporated in dietary interventions for this population.

PMID- 24852203
TI  - PHF8 and REST/NRSF co-occupy gene promoters to regulate proximal gene expression.
AB  - Chromatin regulators play an important role in the development of human diseases.
      In this study, we focused on Plant Homeo Domain Finger protein 8 (PHF8), a
      chromatin regulator that has attracted special concern recently. PHF8 is a
      histone lysine demethylase ubiquitously expressed in nuclei. Mutations of PHF8
      are associated with X-linked mental retardation. It usually functions as a
      transcriptional co-activator by associating with H3K4me3 and RNA polymerase II.
      We found that PHF8 may associate with another regulator, REST/NRSF, predominately
      at promoter regions via studying several published PHF8 chromatin
      immunoprecipitation-sequencing (ChIP-Seq) datasets. Our analysis suggested that
      PHF8 not only activates but may also repress gene expression. 

PMID- 24852204
TI  - 'Scarless' laparoscopic urologic surgery by the combination of mini-laparoscopic
      and laparoendoscopic single-site surgery equipment.
AB  - OBJECTIVE: We evaluated reconstructive and oncological laparoendoscopic single
      site surgery (LESS) combined with mini-laparoscopic instruments as standard
      equipment. PATIENTS AND METHODS: 30 patients underwent reconstructive and
      oncological LESS: mini-laparoscopic-assisted LESS pyeloplasty (LESS-P, n = 18),
      mini-laparoscopic-assisted LESS partial nephrectomy (LESS-PN, n = 7) or mini
      laparoscopic-assisted LESS radical prostatectomy (LESS-RP, n = 5). Perioperative
      data were prospectively collected. RESULTS: The 18 LESS-P cases had operative
      times ranging between 120 and 180 min (average 147.9 min). Estimated blood loss
      ranged between 100 and 300 ml (average 202.1 ml). Two patients required
      additional management for failed reconstruction. LESS-PN was performed in 7
      patients with tumor size ranging between 2.5 and 3.8 cm (average 2.7 cm). Average
      operative time and blood loss were 155 (140-180) min and 321.4 (250-550) ml,
      respectively. Renal artery clamping took place in 1 case. LESS-RP was performed
      in 5 patients; average operative time was 156 (140-180) min and average blood
      loss 196 (100-400) ml. Functional and oncological outcome was directly comparable
      to laparoscopic radical prostatectomy. CONCLUSION: The combination of LESS and
      mini-laparoscopic instrumentation as routine equipment of reconstructive LESS
      reveals a different perspective for 'scarless' urologic surgery.

PMID- 24852205
TI  - The incidence of and risk factors for developing atypical femoral fractures in
      Japan.
AB  - The long-term treatment with anti-resorptive drugs for osteoporotic patients is
      suggested to be associated with an increase in atypical femoral fractures (AFFs).
      However, their incidence, patient characteristics, and risk factors have not been
      fully elucidated especially in Asian countries. This retrospective observational
      cohort study found fourteen AFFs in ten patients (four bilateral fractures) among
      2,238 hip and femoral shaft fractures treated in our associated hospitals between
      2005 and 2010; this incidence (0.63%) was similar to Caucasians. Of the ten
      patients with AFFs, nine (90%) and six (60%) were using bisphosphonates (BPs) and
      glucocorticoids (GCs), respectively, compared to 14.3 and 8.6% for patients with
      typical femoral fractures who were using these agents. As comorbid conditions,
      five patients had collagen disease (CD) and two had diabetes. A fracture location
      , age- and gender-matched (1:3) case-control study revealed that administration
      of BPs, GCs, and suffering from collagen disease (CD) were significant risk
      factors for developing AFFs [odds ratios 36.0 (95% confidence intervals 3.8
      342.2), 13.0 (2.3-74.1) and 9.0 (1.6-50.3), respectively]. Interestingly, all of
      the patients with atypical subtrochanteric femoral fractures, defined as those
      within 5 cm of the lesser trochanter, were taking GCs due to CD, and the age of
      these patients (average of 54.8 years) was significantly younger than those with
      atypical diaphyseal femoral fractures (average of 77.2 years, p < 0.05). In
      conclusion, the incidence of AFFs in the Japanese population was similar to that
      of Caucasians, and taking BPs and GCs and suffering from CD were risk factors for
      developing AFFs.

PMID- 24852206
TI  - Wound classification reporting in HPB surgery: can a single word change public
      perception of institutional performance?
AB  - INTRODUCTION: The drive to improve outcomes and the inevitability of mandated
      public reporting necessitate uniform documentation and accurate databases. The
      reporting of wound classification in patients undergoing hepato-pancreatico
      biliary (HPB) surgery and the impact of inconsistencies on quality metrics were
      investigated. METHODS: The 2005-2011 National Surgical Quality Improvement
      Program (NSQIP) participant use file was interrogated to identify patients
      undergoing HPB resections. The effect of wound classification on post-operative
      surgical site infection (SSI) rates was determined through logistic regression.
      The impact of variations in wound classification reporting on perceived outcomes
      was modelled by simulating observed-to-expected (O/E) ratios for SSI. RESULTS: In
      total, 27,376 patients were identified with significant heterogeneity in wound
      classification. In spite of clear guidelines prompting at least 'clean
      contaminated' designation for HPB resections, 8% of all cases were coded as
      'clean'. Contaminated [adjusted odds ratio (AOR): 1.39, P = 0.001] and dirty
      (AOR: 1.42, P = 0.02] cases were associated with higher odds of SSI, whereas
      clean-contaminated were not (P = 0.99). O/E ratios were highly sensitive to
      modest changes in wound classification. CONCLUSIONS: Perceived performance is
      affected by heterogeneous reporting of wound classification. As institutions work
      to improve outcomes and prepare for public reporting, it is imperative that all
      adhere to consistent reporting practices to provide accurate and reproducible
      outcomes.

PMID- 24852208
TI  - Efficacy of language-appropriate cueing on micrographia in Korean patients with
      Parkinson's disease.
AB  - AIM: First, we objectively quantified the handwriting size of Parkinson's disease
      (PD) patients. Second, we investigated the efficacy of the external visual cueing
      on Korean handwriting in PD. METHODS: We recruited 57 patients diagnosed with PD
      and 37 community-dwelling normal older adults. All participants were asked to
      write a target word on a blank sheet of paper. For investigating the external
      visual cueing, 24 PD patients wrote the target word in square grids. The size of
      each syllable of the word was measured using a public domain software program. In
      order to measure the area of a syllable, the upper, lower, left and right margins
      of the syllable were outlined with a rectangle. The area of selection in square
      pixels or in calibrated square units was used to spatially calibrate the image
      automatically. RESULTS: The PD group showed significantly smaller writing size
      than the normal group in all syllables of the free writing. The writing size in
      the square grids of the PD patients was bigger than their free writing.
      CONCLUSION: The present study is noteworthy, because it is the first attempt to
      use a software program to objectively quantify parkinsonian handwriting size.
      This measuring system would help clinicians monitor handwriting size throughout
      the disease course. From the perspective of rehabilitation, language-appropriate
      external visual cues might be useful in daily communication (i.e. handwriting)
      activities in Korean patients with PD.

PMID- 24852207
TI  - Application of the Rosner-Wei risk-prediction model to estimate sexual
      orientation patterns in colon cancer risk in a prospective cohort of US women.
AB  - PURPOSE: We examined whether lesbian and bisexual women may be at greater risk of
      colon cancer (CC) than heterosexual women. METHODS: Working with a large cohort
      of US women ages 25-64 years, we analyzed 20 years of prospective data to
      estimate CC incidence, based on known risk factors by applying the Rosner-Wei CC
      risk-prediction model. Comparing to heterosexual women, we calculated for lesbian
      and bisexual women the predicted 1-year incidence rate (IR) per 100,000 person
      years and estimated incidence rate ratios (IRR) and 95 % confidence intervals
      (CI), based on each woman's comprehensive risk factor profile. RESULTS: Analyses
      included 1,373,817 person-years of data from 66,257 women. For each sexual
      orientation group, mean predicted 1-year CC IR per 100,000 person-years was
      slightly over 12 cases for each of the sexual orientation groups. After
      controlling for confounders in fully adjusted models and compared with
      heterosexuals, no significant differences in IRR were observed for lesbians (IRR
      1.01; 95 % CI 0.99, 1.04) or bisexuals (IRR 1.01; 95 % CI 0.98, 1.04).
      CONCLUSIONS: CC risk is similar across all sexual orientation subgroups, with all
      groups comparably affected. Health professionals must ensure that prevention,
      screening, and treatment programs are adequately reaching each of these
      communities.

PMID- 24852211
TI  - The 24th american Peptide symposium.

PMID- 24852209
TI  - [What happens to therapeutic changes decided during hospitalization in an
      internal medicine ward? A two-month single-centre prospective study in France].
AB  - PURPOSE: During a hospitalization in an internal medicine department, drug
      prescriptions are frequently modified. We studied the course of these therapeutic
      changes after patients' discharge. METHODS: Eighty-four patients with a long-term
      drug prescription and a registered general practitioner were included on the day
      of their discharge from an internal medicine department in Paris. Their
      medications before and after the hospitalization were established according to
      the discharge letter, and patients were contacted two months after discharge in
      order to assess the modifications that could have occurred during these two
      months after discharge. RESULTS: Medications prescribed before the admission were
      often preserved, 17.7% were withdrawn, and 7% were switched to another
      medication. Two months after discharge, 85% of the modifications were maintained,
      the discharge drug prescription was renewed without a change for 77% of the
      patients. The drug classes that were the more frequently modified during the
      hospital stay were the antihypertensive therapies, with 65% of sustained
      modifications at two months, and analgesics, with 75% of sustained modifications.
      Therapeutic changes that were explained in the discharge letter were more
      frequently preserved at two months than those that were not explained (100%
      versus 79%, 95%CI of the difference [0.09-0.27]; P<0.0001). CONCLUSION:
      Therapeutic changes decided during a hospitalization in an internal medicine unit
      and prescribed at discharge are mostly preserved in outpatients two months after
      discharge, especially when the modifications are explained in the discharge
      letter.

PMID- 24852212
TI  - Single and dual drug selection for transgenes following bombardment of
      Caenorhabditis species.
AB  - The use of drugs and drug resistance genes is a powerful method to select for the
      presence of a transgene. Unlike methods that require the complementation of a
      genetic mutation, this system can be used on any genetic background. Drug
      selection does not require extensive manipulation or costly equipment, yet it is
      very rapid and can achieve extremely high efficiency, selecting a small number of
      transgenic worms from among millions of non-transgenic worms. Introducing
      integrated transgenes into Caenorhabditis elegans by microparticle bombardment
      represents just such a challenge. Here we describe in detail the protocol we have
      developed for dual-drug selection in liquid with puromycin and G418 which works
      well in a variety of Caenorhabditis species. We also show that single drug
      selection with only puromycin or only G418 is effective in C. elegans. The
      growing number of drug selection markers that have been adapted to C. elegans are
      an important addition to the genetic toolkit at our disposal. 

PMID- 24852214
TI  - Modeling of cell culture damage and recovery leads to increased antibody and
      biomass productivity in CHO cell cultures.
AB  - The development of an efficient and productive cell-culture process requires a
      deep understanding of intracellular mechanisms and extracellular conditions for
      optimal product synthesis. Mathematical modeling provides an effective strategy
      to predict, control, and optimize cell performance under a range of culture
      conditions. In this study, a mathematical model is proposed for the investigation
      of cell damage of a Chinese hamster ovary cell culture secreting recombinant anti
      RhD monoclonal antibody (mAb). Irreversible cell damage was found to be
      correlated with a reduction in pH. This irreversible damage to cellular function
      is described mathematically by a Tessier-based model, in which the actively
      growing fraction of cells is dependent on an intracellular metabolic product
      acting as a growth inhibitor. To further verify the model, an offline model-based
      optimization of mAb production in the cell culture was carried out, with the goal
      of minimizing cell damage and thereby enhancing productivity through intermittent
      refreshment of the culture medium. An experimental implementation of this model
      based strategy resulted in a doubling of the yield as compared to the batch
      operation and the resulting biomass and productivity profiles agreed with the
      model predictions. 

PMID- 24852213
TI  - Epidermal cells help coordinate leukocyte migration during inflammation through
      fatty acid-fuelled matrix metalloproteinase production.
AB  - In addition to satisfying the metabolic demands of cells, mitochondrial
      metabolism helps regulate immune cell function. To date, such cell-intrinsic
      metabolic-immunologic cross-talk has only been described operating in cells of
      the immune system. Here we show that epidermal cells utilize fatty acid beta
      oxidation to fuel their contribution to the immune response during cutaneous
      inflammation. By live imaging metabolic and immunological processes within intact
      zebrafish embryos during cutaneous inflammation, we uncover a mechanism where
      elevated beta-oxidation-fuelled mitochondria-derived reactive oxygen species
      within epidermal cells helps guide matrix metalloproteinase-driven leukocyte
      recruitment. This mechanism requires the activity of a zebrafish homologue of the
      mammalian mitochondrial enzyme, Immunoresponsive gene 1. This study describes the
      first example of metabolic reprogramming operating within a non-immune cell type
      to help control its contribution to the immune response. Targeting of this
      metabolic-immunologic interface within keratinocytes may prove useful in treating
      inflammatory dermatoses. 

PMID- 24852215
TI  - Chitosan and silver nanoparticles: promising anti-toxoplasma agents.
AB  - Toxoplasmosis is a worldwide infection caused by obligate intracellular protozoan
      parasite which is Toxoplasma gondii. Chitosan and silver nanoparticles were
      synthesized to be evaluated singly or combined for their anti-toxoplasma effects
      as prophylaxis and as treatment in the experimental animals. Results were
      assessed through studying the parasite density and the ultrastructural parasite
      changes, and estimation of serum gamma interferon. Weight of tissue silver was
      assessed in different organs. Results showed that silver nanoparticles used
      singly or combined with chitosan have promising anti-toxoplasma potentials. The
      animals that received these compounds showed statistically significant decrease
      in the mean number of the parasite count in the liver and the spleen, when
      compared to the corresponding control group. Light microscopic examination of the
      peritoneal exudates of animals receiving these compounds showed stoppage of
      movement and deformity in shape of the tachyzoites, whereas, by scanning electron
      microscope, the organisms were mutilated. Moreover, gamma interferon was
      increased in the serum of animals receiving these compounds. All values of silver
      detected in different tissues were within the safe range. Thus, these
      nanoparticles proved their effectiveness against the experimental Toxoplasma
      infection. 

PMID- 24852217
TI  - Insights into regulatory molecules of intestinal epithelial cell turnover during
      experimental infection by Heterophyes heterophyes.
AB  - Heterophyiasis is an intestinal disease that remains endemic in many parts of the
      world, particularly the Nile Delta of Egypt and Southeast Asia, yet the
      populations at risk of infection expand throughout the world. The main
      histopathological feature of infection is villous atrophy, but the underlying
      factors are not well understood. Apoptosis of the villous epithelial cells was
      previously reported to be enhanced during intestinal parasitic infections;
      however, the role of Heterophyes heterophyes on enterocyte apoptosis was to be
      explored. Therefore, intestinal sections from mice experimentally infected with
      H. heterophyes were studied histopathologically and immunohistochemically for
      caspase-3 and NF-kappaB and compared to non-infected control mice. Atrophic villi
      covered by poorly differentiated epithelial cells were observed in the 2nd week
      post-infection. Also, we noted marked hyperplasia of the intestinal crypts with
      abundant inflammatory cellular infiltrate in the lamina propria, as well as
      apoptosis of cells lining the intestinal villi. Both caspase-3 and NF-kappaB
      showed positive staining in the intestinal epithelial cells with varying grades
      of intensity over the length of infection. Caspase-3 expression rose at the 2nd
      week p.i. then decreased over time, whereas NF-kappaB expression showed
      progressive increase throughout the weeks of infection. In conclusion, caspase-3
      activation may be an important factor in the apoptotic pathway in early
      heterophyiasis, and, on the other hand, NF-kappaB seems to play a role in
      protecting the intestinal cells from excessive apoptosis. These observations may
      help open new avenues for tissue protective therapies that avoid or control the
      deleterious processes of apoptosis in various inflammatory conditions. 

PMID- 24852216
TI  - Determination of parasitic load in different tissues of murine toxoplasmosis
      after immunization by excretory-secretory antigens using Real time QPCR.
AB  - Excretory-secretory antigens (ESAs) of Toxoplasma gondii are one of the
      candidates for immunization against toxoplasmosis. For evaluation of
      immunization, we determined the kinetics of the distribution of Toxoplasma and
      parasite load in different tissues of mice immunized by ESAs. In this
      experimental study, 36 mice in case (n=18) and control (n=18) groups were
      immunized with ESAs and PBS, respectively. After 2weeks, mice were challenged
      intraperitoneally with Toxoplasma virulent RH strain. Blood and different tissues
      (brain, spleen, liver, heart, kidney, and muscle) were collected daily after
      challenge (1, 2, 3 and last day before death). Parasite load was calculated using
      Real time QPCR targeted at the B1 gene. ESAs as vaccine in different tissues
      showed various effects. However, infected mice which received the vaccine in
      comparison with control group, displayed a drastically decreasing in parasite
      burden, in their blood and tissues (P=0.000). These results indicated that ESAs
      with reduction of parasite load in different tissues of host could be evaluable
      candidate for the development of immunization strategies against toxoplasmosis. 

PMID- 24852219
TI  - Peripheral blood features of acute myeloid leukemia with myelodysplasia-related
      changes developing in a patient with sickle cell anemia.

PMID- 24852218
TI  - Could hyponatremia be a marker of anastomotic leakage after colorectal surgery? A
      single center analysis of 1,106 patients over 5 years.
AB  - PURPOSE: The aim of this study is to define the significance of hyponatremia as a
      marker of anastomotic leakage after colorectal surgery. METHODS: All anastomoses
      in colorectal surgery performed at a single institution between July 2007 and
      July 2012 (n = 1,106) were retrospectively identified. Serum sodium levels and
      leukocyte values measured when an anastomotic leak was diagnosed by CT scan
      and/or surgical reintervention (n = 81) were compared to the values preferably on
      postoperative day 5 in the absence of an anastomotic leak (n = 1,025). RESULTS:
      The leak rate in anastomoses of the rectum was 9.0 %, while the leak rate of the
      other anastomoses was 5.4 %. Mean serum sodium level was 138.8 mmol/l in the
      group with an anastomotic leak and 140.5 mmol/l in the group without.
      Hyponatremia (<136 mmol/l) was present in 23 % of patients in the group with an
      anastomotic leak and in 15 % in the group without (p < 0.001). In multivariate
      analysis, leukocytes and serum sodium level remained as significant markers of an
      anastomotic leak. As a marker of an anastomotic leak, hyponatremia had a
      specificity of 93 % and a sensitivity of 23 %, while the presence of either
      leukocytosis or hyponatremia had a sensitivity of 68 %, a specificity of 75 %, a
      positive predictive value of 18 %, and a negative predictive value of 97 %.
      CONCLUSIONS: Hyponatremia could be a specific and relevant marker of anastomotic
      leakage after colorectal surgery. If hyponatremia and leukocytosis are present
      after colorectal surgery, anastomotic leakage should be suspected and a CT scan
      with rectal contrast dye is recommended.

PMID- 24852220
TI  - Young adolescents' perceptions, patterns, and contexts of energy drink use. A
      focus group study.
AB  - Caffeinated energy drinks (EDs) are purported to increase energy and improve
      performance, but have been associated with adverse health effects and death. EDs
      are popular among adolescents and young adults, yet little is known about their
      use among young adolescents. This study explored perceptions, patterns, and
      contexts of ED use in six focus groups with 40 adolescents aged 12-15 years from
      two regional Australian schools. A thematic analysis of the data was used to
      investigate knowledge about ED brands and content, ED use, reasons for ED use,
      physiological effects, and influences on ED use. Participants were familiar with
      EDs and most had used them at least once but had limited knowledge of ED
      ingredients, and some had difficulty differentiating them from soft and sports
      drinks. EDs were used as an alternative to other drinks, to provide energy, and
      in social contexts, and their use was associated with short-term physiological
      symptoms. Parents and advertising influenced participants' perceptions and use of
      EDs. These findings suggest young adolescents use EDs without knowing what they
      are drinking and how they are contributing to their personal risk of harm. The
      advertising, appeal, and use of EDs by adolescents appear to share similarities
      with alcohol and tobacco. Further research is needed to replicate and extend the
      current findings, informed by the lessons learned in alcohol research. 

PMID- 24852221
TI  - Tailoring compensation effects of health-unrelated food properties.
AB  - With the steady rise of the adiposity epidemic, there are increasing calls to
      stimulate healthier food choices. This is difficult, however, because consumers
      hold the nearly universal belief that healthy foods are less tasty. To increase
      their attractiveness, optimizing certain health-unrelated food attributes may
      help compensate for the loss in taste that is caused by the reduction of fat or
      sugar. The overall objective of this paper is to examine the boundary conditions
      under which such compensation effects emerge. Using the example of cookies, we
      examine how compensation effects depend on (i) the consumer segment, (ii) the
      configuration of the food product, and (iii) the type of evaluation process. This
      paper empirically tests compensation effects for optimized flavor intensity. We
      apply a combination of adaptive conjoint analysis and sensory preference tests.
      Market simulations and sensitivity analyses demonstrate that the intricate
      interplay among the three contingency variables is far more important than the
      question of whether compensation effects emerge or not. The analyses uncover four
      distinct segments and they show that compensation effects depend on which type of
      health-related attribute is reduced and whether the health-unrelated attribute is
      improved intrinsically or extrinsically. 

PMID- 24852223
TI  - A chronic fatigue syndrome model demonstrates mechanical allodynia and muscular
      hyperalgesia via spinal microglial activation.
AB  - Patients with chronic fatigue syndrome (CFS) and fibromyalgia syndrome (FMS)
      display multiple symptoms, such as chronic widespread pain, fatigue, sleep
      disturbance, and cognitive dysfunction. Abnormal pain sensation may be the most
      serious of these symptoms; however, its pathophysiology remains unknown. To
      provide insights into the molecular basis underlying abnormal pain in CFS and
      FMS, we used a multiple continuous stress (CS) model in rats, which were housed
      in a cage with a low level of water (1.5 cm in depth). The von Frey and Randall
      Seritto tests were used to evaluate pain levels. Results showed that mechanical
      allodynia at plantar skin and mechanical hyperalgesia at the anterior tibialis
      (i.e., muscle pain) were induced by CS loading. Moreover, no signs of
      inflammation and injury incidents were observed in both the plantar skin and leg
      muscles. However, microglial accumulation and activation were observed in L4-L6
      dorsal horn of CS rats. Quantification analysis revealed a higher accumulation of
      microglia in the medial part of Layers I-IV of the dorsal horn. To evaluate an
      implication of microglia in pain, minocycline was intrathecally administrated
      (via an osmotic pump). Minocycline significantly attenuated CS-induced mechanical
      hyperalgesia and allodynia. These results indicated that activated microglia were
      involved in the development of abnormal pain in CS animals, suggesting that the
      pain observed in CFS and FMS patients may be partly caused by a mechanism in
      which microglial activation is involved.

PMID- 24852222
TI  - Aberrant DNA methylation in ES cells.
AB  - Both mouse and human embryonic stem cells can be differentiated in vitro to
      produce a variety of somatic cell types. Using a new developmental tracing
      approach, we show that these cells are subject to massive aberrant CpG island de
      novo methylation that is exacerbated by differentiation in vitro. Bioinformatics
      analysis indicates that there are two distinct forms of abnormal de novo
      methylation, global as opposed to targeted, and in each case the resulting
      pattern is determined by molecular rules correlated with local pre-existing
      histone modification profiles. Since much of the abnormal methylation generated
      in vitro appears to be stably maintained, this modification may inhibit normal
      differentiation and could predispose to cancer if cells are used for replacement
      therapy. Excess CpG island methylation is also observed in normal placenta,
      suggesting that this process may be governed by an inherent program. 

PMID- 24852224
TI  - Biotechnological potential of the seaweed Cladophora rupestris (Chlorophyta,
      Cladophorales) lipidic extract.
AB  - Recently, with the advent of modern technologies, various marine organisms
      including algae are being studied as sources of natural substances effective on
      classical microorganisms and able to also combat the new trend of acquired
      resistance in microbes. In the present study the antimicrobial activity of the
      lipidic extract of the green seaweed Cladophora rupestris collected in a
      Mediterranean area, in two sampling periods (January and April), was assayed. The
      chemical characterization of the lipidic fractions was performed by gas
      chromatography and multinuclear and multidimensional NMR spectroscopy. In the
      lipidic extract of C. rupestris collected in January an antibacterial activity
      against Enterococcus sp., Streptococcus agalactiae and Vibrio cholerae non-O1 was
      recorded; by contrast, bacterial inhibition was measured on several Vibrio
      species only in April. The fatty acid profile of C. rupestris lipidic extract,
      analyzed by gas chromatography, resulted mainly composed of palmitic, myristic,
      oleic, alpha linolenic, palmitoleic and linoleic acids. Moreover, since alpha
      linolenic acid was the predominant omega3 fatty acid in April, we suggest its
      involvement in the antibacterial activity observed in this month, taking also
      into account that pure alpha-linolenic acid resulted effective towards some
      vibrios strains. C. rupestris fatty acid profile revealed also an interesting
      composition in polyunsaturated fatty acids in both the considered periods with
      the omega6/omega3 ratio lower than 1, leading to conclude that this macroalga may
      be employed as a natural source of omega3. Finally, the (1)H NMR spectrum in
      CDCl3 of algal lipid fractions showed the characteristic signals of saturated
      (SAFAs) and unsaturated fatty acids (UFAs) as well as other metabolites and a
      marked difference in free fatty acids (FFAs) content for the two examined algal
      lipid fractions. It is noteworthy that C. rupestris lipidic extracts show, by NMR
      spectroscopy, the signal pattern of polyhydroxybutyrate, a natural biocompatible
      and biodegradable polymer. In conclusion, on account of its antimicrobial
      activity, nutritional value and bioplastic content, C. rupestris lipidic extract
      can be considered a promising source for future biotechnological applications. 

PMID- 24852225
TI  - Newly identified precipitating factors in mechanical ventilation-induced brain
      damage: implications for treating ICU delirium.
AB  - Delirium is 1.5 to 4.1 times as likely in intensive care unit patients when they
      are mechanically ventilated. While progress in treatment has occurred, delirium
      is still a major problem in mechanically ventilated patients. Based on studies of
      a murine mechanical ventilation model, we summarize evidence here for a novel
      mechanism by which such ventilation can quickly initiate brain damage likely to
      cause cognitive deficits expressed as delirium. That mechanism consists of
      aberrant vagal sensory input driving sustained dopamine D2 receptor (D2R)
      signaling in the hippocampal formation, which induces apoptosis in that brain
      area within 90 min without causing hypoxia, oxidative stress, or inflammatory
      responses. This argues for minimizing the duration and tidal volumes of
      mechanical ventilation and for more effectively reducing sustained D2R signaling
      than achieved with haloperidol alone. The latter might be accomplished by
      reducing D2R cell surface expression and D2R-mediated Akt inhibition by elevating
      protein expression of dysbindin-1C.

PMID- 24852226
TI  - Highlights on corticospinal damage and movement control from the commemorative
      symposium honoring the retirement of Professor Roger Lemon.
AB  - A symposium entitled "Motor control: from the periphery to the cortex and back'
      was held at the University College London Institute of Neurology to commemorate
      the retirement of Professor Roger Lemon, whose research has significantly
      advanced the field of fine motor cortical control. This report focuses on
      discussions at the symposium regarding the descending tracts associated with
      motor control, highlighting the neurological response and subsequent
      rehabilitation of motor pathway damage resulting from cerebrovascular insults.

PMID- 24852227
TI  - Understanding the cause of sporadic Alzheimer's disease.
AB  - The increasing prevalence of Alzheimer's disease (AD) and a lack of effective
      prevention or disease-modifying therapies are global challenges with devastating
      personal, social and economic consequences. The amyloid beta (Abeta) hypothesis
      posits that cerebral beta-amyloidosis is a critical early event in AD
      pathogenesis. However, failed clinical trials of Abeta-centric drug candidates
      have called this hypothesis into question. Whereas we acknowledge that the Abeta
      hypothesis is far from disproven, we here re-visit the links between Abeta, tau
      and neurodegeneration. We review the genetics, epidemiology and pathology of
      sporadic AD and give an updated account of what is currently known about the
      molecular pathogenesis of the disease.

PMID- 24852228
TI  - Corticolimbic connectivity as a possible biomarker for bipolar disorder.
AB  - Bipolar disorder is a severe, disabling and life-threatening illness, which
      affects nearly 2% of the general population. The identification of reliable and
      objective biomarkers may aid early diagnosis and optimize treatment efficacy.
      Through a careful overview of the neuroimaging studies which investigated the
      structural, functional, and effective connectivity in bipolar disorder, we
      explored the role of a disconnected cortico-limbic circuitry in the development
      and maintenance of the disorder. This review offers perspectives and suggestions
      for future research, in order to propose the corticolimbic disconnection as a
      neurobiological underpinning and biomarker for bipolar psychopathology.

PMID- 24852229
TI  - Therapeutic cell carriers: a potential road to cure glioma.
AB  - Many different experimental molecular therapeutic approaches have been evaluated
      in an attempt to treat brain cancer. However, despite the success of these
      experimental molecular therapies, research has shown that the specific and
      efficient delivery of therapeutic agents to tumor cells is a limitation. In this
      regard, cell carrier systems have garnered significant attraction due to their
      capacity to be loaded with therapeutic agents and carry them specifically to
      tumor sites. Furthermore, cell carriers can be genetically modified to express
      therapeutic agents that can directly eradicate cancerous cells or can modulate
      tumor microenvironments. This review describes the current state of cell
      carriers, their use as vehicles for the delivery of therapeutic agents to brain
      tumors, and future directions that will help overcome the present obstacles to
      cell carrier mediated therapy for brain cancer.

PMID- 24852231
TI  - Clinical management of epileptic encephalopathies of childhood and infancy.
AB  - Epileptic encephalopathies represent a group of devastating epileptic disorders
      that appear early in life and are characterized by pharmacoresistant generalized
      or focal seizures, persistent severe EEG abnormalities, and cognitive dysfunction
      or decline. The ictal and interictal epileptic discharges are age-specific and
      are either the main cause or contribute to cognitive deterioration in the
      idiopathic or symptomatic group respectively. Despite choosing the most
      appropriate anti-seizure drugs for the seizure-type and syndrome the results are
      often disappointing and polytherapy and/or alternative therapy becomes
      unavoidable. In those cases, consideration should be given to the quality of life
      of the child and carers. In this review we will discuss the clinical and EEG
      characteristics, evolution and management of age-related epileptic
      encephalopathies, recognized by the International League Against Epilepsy.

PMID- 24852230
TI  - Advances in understanding spontaneous intracerebral hemorrhage: insights from
      neuroimaging.
AB  - Spontaneous (non-traumatic) symptomatic intracerebral hemorrhage is a devastating
      form of stroke, with very high overall mortality and morbidity. Even with the
      best current medical or surgical treatment, outcomes still remain poor. By
      contrast with ischemic stroke, the incidence of intracerebral hemorrhage is not
      decreasing. Indeed, the incidence of intracerebral hemorrhage related to
      antithrombotic drugs, including oral anticoagulants, has increased in recent
      decades. Despite the clear unmet research need for both prevention and acute
      treatment, there has, until recently, been limited progress in understanding the
      pathogenesis of this disease. New advances, especially related to neuroimaging
      biomarkers, are rapidly increasing our understanding of the spectrum of
      mechanisms of brain injury in intracerebral hemorrhage. The aim of this article
      is to review recent insights from neuroimaging studies into the pathophysiology
      and causes of intracerebral hemorrhage, focusing on MRI. We also discuss some of
      the current and future challenges facing clinicians in understanding and treating
      intracerebral hemorrhage.

PMID- 24852232
TI  - Monoamine oxidase and alpha-synuclein as targets in Parkinson's disease therapy.
AB  - The degeneration of dopaminergic neurons in Parkinson's disease (PD) is suggested
      to be associated with the generation of cytotoxic products from dopamine (DA)
      metabolism and the formation of fibrillar inclusions of the protein alpha
      synuclein (AS). Despite of the role of AS in the pathogenesis of PD is not
      completely understood, the stabilization of nontoxic aggregates could represent a
      potential therapeutic route. In respect to the DA metabolism, a well-established
      strategy is the inhibition of the enzyme monoamine oxidase, which is responsible
      to catalyze the major route of inactivation of neurotransmitters. Although
      pharmacological strategies to treat different aspects of the parkinsonian
      condition are under investigation, the development of multifunctional molecules
      that act simultaneously on different targets associated to PD has gained
      attention only recently. In this work we examine the biochemical properties of
      synthetic and natural molecules that are capable of interfering on both DA system
      (via monoamine oxidase inhibition) and AS fibrillation.

PMID- 24852234
TI  - The IUPAC International Congresses of Pesticide Chemistry (1963-2014) and Pest
      Management Science: a half-century of progress.
AB  - As we approach the 2014 San Francisco IUPAC Pesticide Chemistry Congress, we
      reflect on the 51 years of such congresses every 4 years since 1963. Meanwhile,
      our journal, Pesticide Science/Pest Management Science, has in parallel
      continually published relevant science for nearly as long (44 years from 1970).

PMID- 24852235
TI  - Interference control in children with reading difficulties.
AB  - Two studies investigated whether the greater Stroop interference reported in
      children with reading difficulties compared to typical readers of the same age
      represents a generalized deficit in interference control or a consequence of
      their reading problems. In Study 1, a color-word Stroop task and a nonverbal task
      involving responses to locations associated with pictures were administered to 23
      children with single word reading difficulties and 22 typically developing
      children matched for age and nonverbal ability. Children with reading
      difficulties showed disproportionate interference effects in the color-word
      Stroop but not the nonverbal task. In Study 2, groups of poor and typical readers
      completed a spatial Stroop task with printed input that did not require a verbal
      response and a nonverbal analogue. Both groups showed comparable interference in
      these two tasks. Thus, the reported problems in the color-word Stroop task in
      children with reading difficulties do not appear to entail general impairments in
      interference control. 

PMID- 24852236
TI  - RNA-Seq and expression microarray highlight different aspects of the fetal
      amniotic fluid transcriptome.
AB  - OBJECTIVE: The aim of this study was to compare the complexity of the amniotic
      fluid supernatant cell-free fetal transcriptome as described by RNA Sequencing
      (RNA-Seq) and gene expression microarrays. METHODS: Cell-free fetal RNA from the
      amniotic fluid supernatant of five euploid mid-trimester samples was divided and
      prepared in tandem for analysis by either the Affymetrix HG-U133 Plus 2.0 Gene
      Chip microarray or Illumina HiSeq. Transcriptomes were assembled and compared on
      the basis of the presence of signal, rank-order gene expression, and pathway
      enrichment using Ingenuity Pathway Analysis (IPA). RNA-Seq data were also
      examined for evidence of alternative splicing. RESULTS: Within individual
      samples, gene expression was strongly correlated (R = 0.43-0.57). Fewer expressed
      genes were observed using RNA-Seq than gene expression microarrays (4158 vs
      8842). Most of the top pathways in the 'Physiological Systems Development and
      Function' IPA category were shared between platforms, although RNA-Seq yielded
      more significant p-values. Using RNA-Seq, examples of known alternative splicing
      were detected in several genes including H19 and IGF2. CONCLUSIONS: In this pilot
      study, we found that expression microarrays gave a broader view of overall gene
      expression, while RNA-Seq demonstrated alternative splicing and specific pathways
      relevant to the developing fetus. The degraded nature of cell-free fetal RNA
      presented technical challenges for the RNA-Seq approach.

PMID- 24852238
TI  - Manganese porphyrin-double stranded DNA complex guided in situ deposition of
      polyaniline for electrochemical thrombin detection.
AB  - In this work, we proposed a novel electrochemical strategy for sensitive
      detection of thrombin (TB) based on in situ generation of polyaniline (PANI) as a
      redox mediator by using a manganese porphyrin-double stranded DNA (MnTMPyP-dsDNA)
      peroxidase-like artificial enzyme mimic as a powerful catalyst and template. 

PMID- 24852237
TI  - Regulation of secondary cell wall biosynthesis by poplar R2R3 MYB transcription
      factor PtrMYB152 in Arabidopsis.
AB  - Poplar has 192 annotated R2R3 MYB genes, of which only three have been shown to
      play a role in the regulation of secondary cell wall formation. Here we report
      the characterization of PtrMYB152, a poplar homolog of the Arabidopsis R2R3 MYB
      transcription factor AtMYB43, in the regulation of secondary cell wall
      biosynthesis. The expression of PtrMYB152 in secondary xylem is about 18 times of
      that in phloem. When expressed in Arabidopsis under the control of either 35S or
      PtrCesA8 promoters, PtrMYB152 increased secondary cell wall thickness, which is
      likely caused by increased lignification. Accordingly, elevated expression of
      genes encoding sets of enzymes in secondary wall biosynthesis were observed in
      transgenic plants expressing PtrMYB152. Arabidopsis protoplast transfection
      assays suggested that PtrMYB152 functions as a transcriptional activator. Taken
      together, our results suggest that PtrMYB152 may be part of a regulatory network
      activating expression of discrete sets of secondary cell wall biosynthesis genes.

PMID- 24852239
TI  - Biomarkers for infertility and recurrent pregnancy loss.

PMID- 24852240
TI  - Hysteroscopy prior to a first IVF treatment cycle: the need for well-performed
      RCT.

PMID- 24852241
TI  - Epstein-Barr virus-positive nodular lymphocyte predominant Hodgkin lymphoma.
AB  - Hodgkin lymphoma (HL) is classified into 2 largely distinct subgroups, namely
      nodular lymphocyte predominant HL (NLPHL) and classic HL (CHL). CHL is further
      divided into nodular sclerosis, lymphocyte-rich, mixed cellularity (MCCHL) and
      lymphocyte-depleted (LDCHL) subtypes. In industrialized nations, Epstein-Barr
      virus (EBV) has been associated with all types of CHL, especially the MCCHL and
      LDCHL subtypes, but is rare in NLPHL. We report 8 cases of EBV-positive NLPHL
      occurring in patients in the United States. All 8 patients have no history of
      immunosuppression and presented with localized or systemic lymphadenopathy.
      Histologically, 6 cases had a vaguely nodular pattern and 2 cases had a nodular
      and diffuse pattern. In all cases, lymphocyte predominant (LP) cells were
      observed in a background of small lymphocytes and histiocytes.
      Immunohistochemical analysis showed that the LP cells in all cases were positive
      for CD20, CD79a, PAX5, OCT2, and CD45 and were negative for CD15. CD30 was
      expressed variably in 7 cases. EBV encoded RNA was present in all LP cells in 5
      cases and in a subset of LP cells in 3 cases. One patient was treated with
      radiation therapy and 7 patients received chemotherapy, including 4 of 7 patients
      who underwent autologous stem cell transplantation. EBV infection is a rare
      primary or secondary event in NLPHL that correlates with poorer prognosis and
      often requires more aggressive therapy. The variable expression of CD30 in most
      of these cases could be the result of EBV infection. 

PMID- 24852242
TI  - Progressive leukemic non-nodal mantle cell lymphoma associated with deletions of
      TP53, ATM, and/or 13q14.
AB  - Leukemic, non-nodal mantle cell lymphoma (MCL) is a relatively indolent disease
      characterized by asymptomatic leukemic presentation, non-nodal disease
      distribution, and slow disease progression, particularly in comparison to that of
      classic nodal MCL. We studied 3 cases of leukemic, non-nodal MCL in which TP53,
      ATM, and/or 13q14 deletions were identified. All three patients had disease
      progression leading to treatment requirements in two of the patients at 5 and 18
      months after initial diagnosis. The third patient also clinically progressed 25
      months after initial diagnosis but was lost to follow up despite recommendation
      for initiation of therapy. We present these cases as potential evidence that
      while leukemic non-nodal MCL is typically an indolent disease compared to
      classically defined mantle cell lymphoma, cytogenetic heterogeneity exists and
      cases with TP53, ATM, and/or 13q14 deletions may have a relatively aggressive
      clinical course. 

PMID- 24852243
TI  - Deep sequencing detects very-low-grade somatic mosaicism in the unaffected mother
      of siblings with nemaline myopathy.
AB  - When an expected mutation in a particular disease-causing gene is not identified
      in a suspected carrier, it is usually assumed to be due to germline mosaicism. We
      report here very-low-grade somatic mosaicism in ACTA1 in an unaffected mother of
      two siblings affected with a neonatal form of nemaline myopathy. The mosaicism
      was detected by deep resequencing using a next-generation sequencer. We
      identified a novel heterozygous mutation in ACTA1, c.448A>G (p.Thr150Ala), in the
      affected siblings. Three-dimensional structural modeling suggested that this
      mutation may affect polymerization and/or actin's interactions with other
      proteins. In this family, we expected autosomal dominant inheritance with either
      parent demonstrating germline or somatic mosaicism. Sanger sequencing identified
      no mutation. However, further deep resequencing of this mutation on a next
      generation sequencer identified very-low-grade somatic mosaicism in the mother:
      0.4%, 1.1%, and 8.3% in the saliva, blood leukocytes, and nails, respectively.
      Our study demonstrates the possibility of very-low-grade somatic mosaicism in
      suspected carriers, rather than germline mosaicism. 

PMID- 24852244
TI  - On the application of Nafion membrane for the preparation of (90)Y skin patches,
      quality control, and biological evaluation for treatment of superficial tumors.
AB  - This article describes the preparation, quality control, and biological
      evaluation of (90)Y-skin patches based on Nafion((r)) membrane as a viable
      treatment modality for superficial skin tumors such as melanoma. To arrive at the
      conditions for optimum uptake of (90)Y on the membrane, influence of various
      experimental parameters, such as pH of the feed solution, inactive yttrium
      carrier concentration, reaction volume, contact time, and temperature, was
      systematically investigated. Under the optimized conditions, >95% of the (90)Y
      activity (37-185 MBq) could be incorporated in the Nafion membranes to prepare
      (90)Y-skin patches. Quality control tests were carried out to ensure
      nonleachability, uniform distribution of activity, and stability of the (90)Y
      patches. Mice bearing transplanted melanoma tumors that were treated with two
      doses of 74 MBq (90)Y-Nafion membrane sources showed complete tumor regression.
      Histopathological examination of the treated area showed absence of tumor. The
      results of the study indicate the potential of (90)Y-Nafion membrane sources for
      treatment of superficial skin tumors.

PMID- 24852245
TI  - Ernest Henry Starling (1866-1927) on the formation and reabsorption of lymph.
AB  - Ernest Henry Starling laid the groundwork for our modern understanding of how the
      interstitial fluid, which he referred to as 'lymph', is regulated. Together with
      his colleague, William Bayliss, he provided the crucial insight into how fluid is
      driven out of the capillary to form interstitial fluid. That was to measure
      (estimate) the capillary pressure in different parts of the circulation and to
      relate changes in these pressures to altered lymph formation. In addressing how
      interstitial fluid re-enters the circulation, he was able to show that this
      occurs not only via the lymphatics, but also by re-entering the capillaries,
      mediated by the oncotic pressure of the plasma proteins. Starling's discoveries
      put to rest all notions that the processes of filtration and reabsorption of
      fluid are mediated by the 'vital activity' of cells. They could be explained
      entirely on the basis of physic-chemical forces. Based upon his insights from
      animal experiments, he was able to explain the genesis of edema (dropsy) in a
      number of disease states, including venous obstruction, cardiac disease and
      inflammatory conditions.

PMID- 24852246
TI  - Generalized psychological distress among HIV-infected patients enrolled in
      antiretroviral treatment in Dilla University Hospital, Gedeo zone, Ethiopia.
AB  - BACKGROUND: Psychological disorders like depression and anxiety are potentially
      dangerous conditions. In the context of HIV/AIDS, this can influence health
      seeking behavior or uptake of diagnosis and treatment for HIV/AIDS, add to the
      burden of disease for HIV patients, create difficulty in adherence to treatment,
      and increase the risk of mortality and morbidity. The objective of this study was
      to assess the prevalence and correlates of generalized psychological distress
      among HIV-infected subjects on antiretroviral treatment (ART). DESIGN: An
      institution-based cross-sectional study was conducted. Interviews were conducted
      with 500 patients initiating ART at Dilla Referral Hospital. Generalized
      psychological distress was measured using the Hospital Anxiety and Depression
      Scale (HADS). A cutoff score >=19 was used to identify possible cases of patients
      with generalized psychological distress. Multivariable logistic regression
      analysis using SPSS Version 20 was performed to identify factors associated with
      psychological distress. RESULTS: The prevalence of generalized psychological
      distress among the population of this study was 11.2% (HADS>=19). Factors
      independently associated with generalized psychological distress were moderate
      stress (OR=6.87, 95% CI 2.27-20.81), low social support (OR=10.17, 95% CI 2.85
      36.29), number of negative life events of six and above (OR=3.99, 95% CI 1.77
      8.99), not disclosing HIV status (OR=5.24, 95% CI 1.33-20.62), and CD4 cell count
      of <200 cells/mm(3) (OR=1.98, 95% CI 0.45-0.83) and 200-499 cells/mm(3) (OR=3.53,
      95% CI 1.62-7.73). CONCLUSIONS: This study provides prevalence of psychological
      distress lower than the prevalence of common mental disorders in Ethiopia and
      comparable to some other studies in sub-Saharan Africa. The findings are
      important in terms of their relevance to identifying high-risk groups for
      generalized psychological distress and preventing distress through integrating
      mental health services with HIV/AIDS care and support program.

PMID- 24852247
TI  - Measuring HIV-related mortality in the first decade of anti-retroviral therapy in
      sub-Saharan Africa.

PMID- 24852248
TI  - pocketZebra: a web-server for automated selection and classification of subfamily
      specific binding sites by bioinformatic analysis of diverse protein families.
AB  - The new web-server pocketZebra implements the power of bioinformatics and
      geometry-based structural approaches to identify and rank subfamily-specific
      binding sites in proteins by functional significance, and select particular
      positions in the structure that determine selective accommodation of ligands. A
      new scoring function has been developed to annotate binding sites by the presence
      of the subfamily-specific positions in diverse protein families. pocketZebra web
      server has multiple input modes to meet the needs of users with different
      experience in bioinformatics. The server provides on-site visualization of the
      results as well as off-line version of the output in annotated text format and as
      PyMol sessions ready for structural analysis. pocketZebra can be used to study
      structure-function relationship and regulation in large protein superfamilies,
      classify functionally important binding sites and annotate proteins with unknown
      function. The server can be used to engineer ligand-binding sites and allosteric
      regulation of enzymes, or implemented in a drug discovery process to search for
      potential molecular targets and novel selective inhibitors/effectors. The server,
      documentation and examples are freely available at
      http://biokinet.belozersky.msu.ru/pocketzebra and there are no login
      requirements. 

PMID- 24852250
TI  - De novo detection of differentially bound regions for ChIP-seq data using peaks
      and windows: controlling error rates correctly.
AB  - A common aim in ChIP-seq experiments is to identify changes in protein binding
      patterns between conditions, i.e. differential binding. A number of peak- and
      window-based strategies have been developed to detect differential binding when
      the regions of interest are not known in advance. However, careful consideration
      of error control is needed when applying these methods. Peak-based approaches use
      the same data set to define peaks and to detect differential binding. Done
      improperly, this can result in loss of type I error control. For window-based
      methods, controlling the false discovery rate over all detected windows does not
      guarantee control across all detected regions. Misinterpreting the former as the
      latter can result in unexpected liberalness. Here, several solutions are
      presented to maintain error control for these de novo counting strategies. For
      peak-based methods, peak calling should be performed on pooled libraries prior to
      the statistical analysis. For window-based methods, a hybrid approach using
      Simes' method is proposed to maintain control of the false discovery rate across
      regions. More generally, the relative advantages of peak- and window-based
      strategies are explored using a range of simulated and real data sets.
      Implementations of both strategies also compare favourably to existing programs
      for differential binding analyses. 

PMID- 24852249
TI  - Identification of a large protein network involved in epigenetic transmission in
      replicating DNA of embryonic stem cells.
AB  - Pluripotency of embryonic stem cells (ESCs) is maintained by transcriptional
      activities and chromatin modifying complexes highly organized within the
      chromatin. Although much effort has been focused on identifying genome-binding
      sites, little is known on their dynamic association with chromatin across cell
      divisions. Here, we used a modified version of the iPOND (isolation of proteins
      at nascent DNA) technology to identify a large protein network enriched at
      nascent DNA in ESCs. This comprehensive and unbiased proteomic characterization
      in ESCs reveals that, in addition to the core replication machinery, proteins
      relevant for pluripotency of ESCs are present at DNA replication sites. In
      particular, we show that the chromatin remodeller HDAC1-NuRD complex is enriched
      at nascent DNA. Interestingly, an acute block of HDAC1 in ESCs leads to increased
      acetylation of histone H3 lysine 9 at nascent DNA together with a concomitant
      loss of methylation. Consistently, in contrast to what has been described in
      tumour cell lines, these chromatin marks were found to be stable during cell
      cycle progression of ESCs. Our results are therefore compatible with a rapid
      deacetylation-coupled methylation mechanism during the replication of DNA in ESCs
      that may participate in the preservation of pluripotency of ESCs during
      replication. 

PMID- 24852251
TI  - StemCellNet: an interactive platform for network-oriented investigations in stem
      cell biology.
AB  - Stem cells are characterized by their potential for self-renewal and their
      capacity to differentiate into mature cells. These two key features emerge
      through the interplay of various factors within complex molecular networks. To
      provide researchers with a dedicated tool to investigate these networks, we have
      developed StemCellNet, a versatile web server for interactive network analysis
      and visualization. It rapidly generates focused networks based on a large
      collection of physical and regulatory interactions identified in human and murine
      stem cells. The StemCellNet web-interface has various easy-to-use tools for
      selection and prioritization of network components, as well as for integration of
      expression data provided by the user. As a unique feature, the networks generated
      can be screened against a compendium of stemness-associated genes. StemCellNet
      can also indicate novel candidate genes by evaluating their connectivity
      patterns. Finally, an optional dataset of generic interactions, which provides
      large coverage of the human and mouse proteome, extends the versatility of
      StemCellNet to other biomedical research areas in which stem cells play important
      roles, such as in degenerative diseases or cancer. The StemCellNet web server is
      freely accessible at http://stemcellnet.sysbiolab.eu. 

PMID- 24852252
TI  - PredHS: a web server for predicting protein-protein interaction hot spots by
      using structural neighborhood properties.
AB  - Identifying specific hot spot residues that contribute significantly to the
      affinity and specificity of protein interactions is a problem of the utmost
      importance. We present an interactive web server, PredHS, which is based on an
      effective structure-based hot spot prediction method. The PredHS prediction
      method integrates many novel structural and energetic features with two types of
      structural neighborhoods (Euclidian and Voronoi), and combines random forest and
      sequential backward elimination algorithms to select an optimal subset of
      features. PredHS achieved the highest performance identifying hot spots compared
      with other state-of-the-art methods, as benchmarked by using an independent
      experimentally verified dataset. The input to PredHS is protein structures in the
      PDB format with at least two chains that form interfaces. Users can visualize
      their predictions in an interactive 3D viewer and download the results as text
      files. PredHS is available at http://www.predhs.org. 

PMID- 24852254
TI  - Diels-Alder reaction of 1,3-diarylbenzo[c]furans with thiophene S,S
      dioxide/indenone derivatives: a facile preparation of substituted
      dibenzothiophene S,S-dioxides and fluorenones.
AB  - One pot syntheses of substituted dibenzothiophene S,S-dioxides and fluorenones
      were successfully achieved by Diels-Alder reaction of benzo[c]furans with
      thiophene S,S-dioxides and indenones, respectively. Photophysical properties of
      representative seven- and nine-membered dibenzothiophene S,S-dioxide acenes were
      also reported. 

PMID- 24852253
TI  - Hydroxyl-radical-induced oxidation of 5-methylcytosine in isolated and cellular
      DNA.
AB  - The methylation and oxidative demethylation of cytosine in CpG dinucleotides
      plays a critical role in the regulation of genes during cell differentiation,
      embryogenesis and carcinogenesis. Despite its low abundance, 5-methylcytosine
      (5mC) is a hotspot for mutations in mammalian cells. Here, we measured five
      oxidation products of 5mC together with the analogous products of cytosine and
      thymine in DNA exposed to ionizing radiation in oxygenated aqueous solution. The
      products can be divided into those that arise from hydroxyl radical (*OH)
      addition at the 5,6-double bond of 5mC (glycol, hydantoin and imidazolidine
      products) and those that arise from H-atom abstraction from the methyl group of
      5mC including 5-hydroxymethylcytosine (5hmC) and 5-formylcytosine (5fC). Based on
      the analysis of these products, we show that the total damage at 5mC is about 2
      fold greater than that at C in identical sequences. The formation of hydantoin
      products of 5mC is favored, compared to analogous reactions of thymine and
      cytosine, which favor the formation of glycol products. The distribution of
      oxidation products is sequence dependent in specific ODN duplexes. In the case of
      5mC, the formation of 5hmC and 5fC represents about half of the total of *OH
      induced oxidation products of 5mC. Several products of thymine, cytosine, 5mC, as
      well as 8-oxo-7,8-dihydroguanine (8oxoG), were also estimated in irradiated
      cells. 

PMID- 24852255
TI  - The effect of 8-week plyometric training on leg power, jump and sprint
      performance in female soccer players.
AB  - The aim of this study was to determine the effect of 8-week plyometric training
      (PT) on the leg power and jump and sprint performance in female soccer players.
      Eighteen female soccer players from Women Second League (age = 18.2 +/- 2.3
      years, height = 161.3 +/- 5.4 cm, body mass = 56.6 +/- 7.2 kg) were randomly
      assigned to control (n = 9) and plyometric (n = 9) groups. Both groups continued
      together with regular technical and tactical soccer training for 4 days a week.
      Additionally, the plyometric group underwent PT for 8 weeks, 1 day per week, 60
      minute session duration. During the 8-week period, the control group was hindered
      from any additional conditioning training. All players' jumps (triple hop,
      countermovement jump, and standing broad jump), running speed (20 m), and peak
      power were evaluated before and after 8 weeks. No significant difference was
      found between the groups at pretest variables (p > 0.05). Significant
      improvements were found in the posttest of both the groups (p <= 0.05), except
      for 20-m sprint test in the control group (p > 0.05). Triple hop distance,
      countermovement jump, standing broad jump, peak power, and 20-m sprint test
      values were all significantly improved in the plyometric group, compared with the
      control group (p <= 0.05). We concluded that short duration PT is an improved
      important component of athletic performance in female soccer players. The results
      indicate that safe, effective, and alternative PT can be useful to strength and
      conditioning coaches, especially during competition season where less time is
      available for training.

PMID- 24852256
TI  - Accuracy of a vertical jump contact mat for determining jump height and flight
      time.
AB  - Several devices are available to measure vertical jump (VJ) height based on
      flight time, VJ reach height, or ground reaction forces. The purpose of this
      study was to determine the accuracy of a VJ mat for measuring flight time and VJ
      height compared with a VJ tester or a force plate. Seventeen men and 18 women (X
      +/- SD; age = 20.9 +/- 0.7 years, height = 176.1 +/- 0.9 cm, weight = 72.6 +/-
      13.5 kg) served as subjects. Subjects performed counter-movement vertical jumps
      while standing on both a force plate (1,000 Hz) and a VJ mat. A Vertec VJ tester
      was used to measure jump reach. Compared with the force plate, the VJ mat
      reported greater VJ height (VJ mat = 0.50 +/- 0.12 m, force plate = 0.34 +/- 0.10
      m) and flight time (VJ mat = 0.629 +/- 0.078 seconds, force plate = 0.524 +/-
      0.077 seconds). Comparison of VJ heights from the VJ mat and the Vertec revealed
      no significant differences (Vertec = 0.48 +/- 0.11 m). Regression analyses
      indicated strong relationships between testing methods and suggested that high VJ
      performances may be underestimated with the VJ mat. This particular VJ mat
      compared favorably with the Vertec but not the force plate. It seems that the
      different flight times derived from the VJ mat may permit the VJ mat to be in
      closer agreement with VJ heights from the Vertec. Also, the VJ mat may not be an
      appropriate tool for assessing high VJ performances (i.e., >=0.70 m; ~28 inches).
      Practitioners and researchers using similar VJ mats may not obtain accurate
      flight times and may underestimate high performers.

PMID- 24852257
TI  - Relationship Between Jump Rope Double Unders and Sprint Performance in Elementary
      Schoolchildren.
AB  - According to dynamic analyses of muscle contraction, jump rope is a typical
      stretch-shortening cycle (SSC) movement. It has been reported that the
      relationship with SSC is higher in double unders than in single unders (basic
      jumps); however, the relationship between jump rope and sprint performances has
      not been extensively studied. To clarify this relationship in elementary
      schoolchildren, we compared the sprint speed and SSC ability of children who were
      grouped according to gender and ability. The subjects were 143 elementary fifth
      and sixth graders (78 boys, 65 girls). The consecutive maximal number of double
      unders, reactivity index (index of SSC ability) by Myotest, and 20-m sprint time
      were measured. According to the mean of jump rope records, the children were
      divided into a superior ability group (more than average + 0.5 SD) and an
      inferior ability group (less than average - 0.5 SD) for each gender. In both
      genders, a significant difference was found in the 20-m sprint time between the
      inferior and superior ability groups. The times for the superior ability groups
      (boys, 3.75 +/- 0.23 seconds; girls, 4.02 +/- 0.24 seconds) were excellent
      compared with the inferior ability groups (boys, 4.17 +/- 0.32 seconds; girls,
      4.23 +/- 0.21 seconds). This effect size was higher in boys (1.44) than in girls
      (0.93). The reactivity index in the superior ability group was excellent compared
      with that in the inferior ability group. In conclusion, children who perform
      better in double unders are also faster during a 20-m sprint run. This tendency
      may be higher in boys. Classic jump rope training, such as double unders, should
      be effective as elementary plyometrics for improving the sprint ability of
      children.

PMID- 24852258
TI  - Validity and reliability of 2 upper-body strength tests for preschool children.
AB  - The "bent knee push-up" and the "timed dipping" are 2 upper-body strength
      assessment tests whose simplicity and ease of use make them suitable to be
      applied to preschool children. Nevertheless, their psychometric properties have
      not been properly studied for this age group. This study aimed to fill this gap.
      To accomplish this, both tests were administered 3 times (familiarization, test,
      and retest) to a group of 120 children (mean age, 48.60 +/- 9.94 months; body
      mass index, 17.05 +/- 2.04 kg.m; 50% girls), with a week interval between each
      assessment. The obtained results in each test were compared with those obtained
      in the "handheld dynamometry" (the criterion measure) with the aim of identifying
      their construct validity. The reliability of the tests was analyzed by comparing
      the obtained results during the second (test) and the third (retest) time that
      each 1 was carried out. Intraclass correlation coefficients (ICCs) were used to
      examine reliability, and Pearson's correlation coefficients were used to examine
      validity. The bent knee push-up showed a moderate reliability for 3-year-old
      children (ICC, 0.690; 95% confidence interval [95% CI], 0.379-0.845) and high for
      those aged 4 years (ICC, 0.848; 95% CI, 0.715-0.919) and 5 (ICC, 0.702; 95% CI,
      0.441-0.841). Similar results were obtained for the timed dipping, in children
      aged 3 years (ICC, 0.522; 95% CI, 0.422-0.761), 4 years (ICC, 0.766; 95% CI,
      0.560-0.875), and 5 years (ICC, 0.828; 95% CI, 0.677-0.908). Both tests showed a
      good construct validity, with the exception of the timed dipping in 3-year-old
      children (r = 0.200; p = 0.256). The results in this study suggest that the bent
      knee push-up and the timed dipping show psychometric properties that make them
      suitable to be used in research carried out with preschoolers.

PMID- 24852259
TI  - Acoustic impedance microscopy for biological tissue characterization.
AB  - A new method for two-dimensional acoustic impedance imaging for biological tissue
      characterization with micro-scale resolution was proposed. A biological tissue
      was placed on a plastic substrate with a thickness of 0.5mm. A focused acoustic
      pulse with a wide frequency band was irradiated from the "rear side" of the
      substrate. In order to generate the acoustic wave, an electric pulse with two
      nanoseconds in width was applied to a PVDF-TrFE type transducer. The component of
      echo intensity at an appropriate frequency was extracted from the signal received
      at the same transducer, by performing a time-frequency domain analysis. The
      spectrum intensity was interpreted into local acoustic impedance of the target
      tissue. The acoustic impedance of the substrate was carefully assessed prior to
      the measurement, since it strongly affects the echo intensity. In addition, a
      calibration was performed using a reference material of which acoustic impedance
      was known. The reference material was attached on the same substrate at different
      position in the field of view. An acoustic impedance microscopy with 200*200
      pixels, its typical field of view being 2*2 mm, was obtained by scanning the
      transducer. The development of parallel fiber in cerebella cultures was clearly
      observed as the contrast in acoustic impedance, without staining the specimen.
      The technique is believed to be a powerful tool for biological tissue
      characterization, as no staining nor slicing is required.

PMID- 24852260
TI  - Picosecond acoustics method for measuring the thermodynamical properties of
      solids and liquids at high pressure and high temperature.
AB  - Based on the original combination of picosecond acoustics and diamond anvils
      cell, recent improvements to accurately measure hypersonic sound velocities of
      liquids and solids under extreme conditions are described. To illustrate the
      capability of this technique, results are given on the pressure and temperature
      dependence of acoustic properties for three prototypical cases: polycrystal
      (iron), single-crystal (silicon) and liquid (mercury) samples. It is shown that
      such technique also enables the determination of the density as a function of
      pressure for liquids, of the complete set of elastic constants for single
      crystals, and of the melting curve for any kind of material. High pressure
      ultrafast acoustic spectroscopy technique clearly opens opportunities to measure
      thermodynamical properties under previously unattainable extreme conditions.
      Beyond physics, this state-of-the-art experiment would thus be useful in many
      other fields such as nonlinear acoustics, oceanography, petrology, in of view. A
      brief description of new developments and future directions of works conclude the
      article. 

PMID- 24852261
TI  - Invited comment on the paper by Benagiano et al. Entitled 'the history of
      endometriosis'.

PMID- 24852262
TI  - Raphe AMPA receptors and nicotinic acetylcholine receptors mediate ketamine
      induced serotonin release in the rat prefrontal cortex.
AB  - Several lines of evidence indicate that ketamine has a rapid antidepressant-like
      effect in rodents and humans, but underlying mechanisms are unclear. In the
      present study, we investigated the effect of ketamine on serotonin (5-HT) release
      in the rat prefrontal cortex by in vivo microdialysis. A subcutaneous
      administration of ketamine (5 and 25 mg/kg) significantly increased the
      prefrontal 5-HT level in a dose-dependent manner, which was attenuated by local
      injection of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor
      (AMPAR) antagonists into the dorsal raphe nucleus (DRN). Direct stimulation of
      AMPARs in the DRN significantly increased prefrontal 5-HT level, while intra-DRN
      injection of ketamine (36.5 nmol) had no effect. Furthermore, intra-DRN injection
      of an alpha 4 beta 2-nicotinic acetylcholine receptor (nAChR) antagonist, dihydro
      beta-erythroidine (10 nmol), significantly attenuated the subcutaneous ketamine
      induced increase in prefrontal 5-HT levels. These results suggest that AMPARs and
      alpha 4 beta 2-nAChRs in the DRN play a key role in the ketamine-induced 5-HT
      release in the prefrontal cortex. 

PMID- 24852264
TI  - Rickettsia conorii israelensis in Rhipicephalus sanguineus ticks, Sardinia,
      Italy.
AB  - The presence of tick-borne Rickettsia spp. was examined by PCR using DNA samples
      extracted from 254 ticks collected from mammals originating from northern and
      eastern Sardinia, Italy. The spotted fever group rickettsial agent Rickettsia
      conorii israelensis was detected in 3 Rhipicephalus sanguineus ticks from a dog
      for the first time in this geographical area. In addition, Ri. massiliae, Ri.
      slovaca, and Ri. aeschlimannii were detected in Rh. turanicus, Rh. sanguineus,
      Dermacentor marginatus, and Hyalomma marginatum marginatum ticks from dogs,
      goats, wild boar, and horse. Moreover, Candidatus Rickettsia barbariae was
      detected in 2 Rh. turanicus ticks from goats. The detection of Ri. conorii
      israelensis, an emergent agent which causes Israeli spotted fever, increases our
      knowledge on tick-borne rickettsioses in Sardinia.

PMID- 24852263
TI  - Physiological Function and Characterization of TRPCs in Neurons.
AB  - Ca2+ entry is essential for regulating vital physiological functions in all
      neuronal cells. Although neurons are engaged in multiple modes of Ca2+ entry that
      regulates variety of neuronal functions, we will only discuss a subset of
      specialized Ca2+-permeable non-selective Transient Receptor Potential Canonical
      (TRPC) channels and summarize their physiological and pathological role in these
      excitable cells. Depletion of endoplasmic reticulum (ER) Ca2+ stores, due to G
      protein coupled receptor activation, has been shown to activate TRPC channels in
      both excitable and non-excitable cells. While all seven members of TRPC channels
      are predominately expressed in neuronal cells, the ion channel properties, mode
      of activation, and their physiological responses are quite distinct. Moreover,
      many of these TRPC channels have also been suggested to be associated with
      neuronal development, proliferation and differentiation. In addition, TRPCs also
      regulate neurosecretion, long-term potentiation and synaptic plasticity.
      Similarly, perturbations in Ca2+ entry via the TRPC channels have been also
      suggested in a spectrum of neuropathological conditions. Hence, understanding the
      precise involvement of TRPCs in neuronal function and in neurodegenerative
      conditions would presumably unveil avenues for plausible therapeutic
      interventions for these devastating neuronal diseases. 

PMID- 24852265
TI  - c-Jun promotes cell migration and drives expression of the motility factor ENPP2
      in soft tissue sarcomas.
AB  - Genomic amplification of the c-Jun proto-oncogene has been identified in ~30% of
      dedifferentiated liposarcomas (DDLPS), but the functional contribution of c-Jun
      to the progression of DDLPS remains poorly understood. In previous work we showed
      that knock-down of c-Jun by RNA interference impaired the in vitro proliferation
      and in vivo growth of a DDLPS cell line (LP6) with genomic amplification of the c
      Jun locus. Here, we used gene expression analysis and functional studies in a
      broad panel of cell lines to further define the role of c-Jun in DDLPS and other
      soft tissue sarcomas. We show that c-Jun knock-down impairs transition through
      the G1 phase of the cell cycle in multiple DDLPS cell lines. We also found that
      high levels of c-Jun expression are both necessary and sufficient to promote
      DDLPS cell migration and invasion in vitro. Our data suggest that high levels of
      c-Jun enhance motility in part by driving the expression of ENPP2/Autotaxin. c
      Jun over-expression has minimal effects on in vitro proliferation but
      substantially enhances the in vivo growth of weakly tumourigenic DDLPS cell
      lines. Finally, we provide evidence that c-Jun genomic amplification and over
      expression may have similar functional consequences in other types of soft tissue
      sarcoma. Our data suggest a model in which relatively low levels of c-Jun are
      sufficient for in vitro proliferation, but high levels of c-Jun enhance
      invasiveness and capacity for in vivo tumour growth. These observations provide
      an explanation for the selective advantage provided by c-Jun genomic
      amplification in vivo and suggest that sarcomas with elevated c-Jun levels are
      likely to have a particularly high malignant potential. Data from exon array and
      RNA-Seq experiments have been deposited in the GEO database (Accession No.
      GSE57531).

PMID- 24852267
TI  - Colloidal membranes of hard rods: unified theory of free edge structure and twist
      walls.
AB  - Monodisperse suspensions of rod like chiral fd viruses are condensed into a rod
      length thick colloidal monolayers of aligned rods by depletion forces. Twist
      deformations of the molecules are expelled to the monolayer edge as in a chiral
      smectic A liquid crystal, and a cholesteric band forms at the edge. Coalescence
      of two such isolated membranes results in a twist wall sandwiched between two
      regions of aligned rods, dubbed pi-walls. By modeling the membrane as a binary
      fluid of coexisting cholesteric and chiral smectic A liquid-crystalline regions,
      we develop a unified theory of the pi-walls and the monolayer edge. The mean
      field analysis of our model yields the molecular tilt profiles, the local
      thickness change, and the crossover from smectic to cholesteric behavior at the
      monolayer edge and across the pi-wall. Furthermore, we calculate the line tension
      associated with the formation of these interfaces. Our model offers insights
      regarding the stability and the detailed structure of the pi-wall and the
      monolayer edge. 

PMID- 24852266
TI  - Edentulism and other variables associated with self-reported health status in
      Mexican adults.
AB  - BACKGROUND: To determine if edentulism, controlling for other known factors, is
      associated with subjective self-report health status (SRH) in Mexican adults.
      MATERIAL AND METHODS: We examined the SRH of 13 966 individuals 35 years and
      older, using data from the National Survey of Performance Assessment, a cross
      sectional study that is part of the technical collaboration between the Ministry
      of Health of Mexico and the World Health Organization, which used the survey
      instrument and sampling strategies developed by WHO for the World Health Survey.
      Sociodemographic, socioeconomic, medical, and behavioral variables were collected
      using questionnaires. Self-reported health was our dependent variable. Data on
      edentulism were available from 20 of the 32 Mexican states. A polynomial logistic
      regression model adjusted for complex sampling was generated. RESULTS: In the
      SRH, 58.2% reported their health status as very good/good, 33.8% said they had a
      moderate health status, and 8.0% reported that their health was bad/very bad. The
      association between edentulism and SRH was modified by age and was significant
      only for bad/very bad SRH. Higher odds of reporting moderate health or poor/very
      poor health were found in women, people with lower socio-economic status and with
      physical disabilities, those who were not physically active, or those who were
      underweight or obese, those who had any chronic disease, and those who used
      alcohol. CONCLUSIONS: The association of edentulism with a self-report of a poor
      health status (poor/very poor) was higher in young people than in adults. The
      results suggest socioeconomic inequalities in SRH. Inequality was further
      confirmed among people who had a general health condition or a disability.
      Dentists and health care professionals need to recognize the effect of edentulism
      on quality of life among elders people.

PMID- 24852268
TI  - Chest physiotherapy for acute wheezing episodes: an inappropriate interpretation
      of the first trial in outpatient infants.

PMID- 24852269
TI  - Investigation of in vitro parameters and in vivo fertility of rabbit spermatozoa
      after chilled storage.
AB  - Artificial insemination (AI) programmes in the rabbit meat industry require
      improved longevity of spermatozoa stored in vitro. Two studies evaluated the
      effects of storage temperature and extender on in vitro quality and fertility of
      rabbit spermatozoa over 96h of chilled storage. In Experiment 1, three ejaculates
      were collected from each of five bucks and diluted 1:10 in either Extender A or
      B, and then divided further for storage at 5 degrees C or 15 degrees C. Sperm
      motility (MOT) was assessed by CASA at 0, 24, 48, 72 and 96h of storage.
      Viability, acrosome integrity, mitochondrial membrane potential (MMP), oxidative
      stress and DNA integrity of the two best extenders were assessed by flow
      cytometry. Extender B at 15 degrees C gave significantly higher values of MOT and
      MMP from 24 and 72h, respectively. At 96h, viability, acrosome and DNA integrity
      were best maintained at 15 degrees C (P<0.05). In contrast, storage at 5 degrees
      C resulted in lower oxidative stress from 72h. In Experiment 2, a pilot study
      examined fertility rates of does inseminated with spermatozoa diluted in Extender
      B and stored at 5 degrees C or 15 degrees C. Sixty seven multiparous does were
      inseminated with spermatozoa stored for 0h (n=12; control), 48h (n=26) or 72h
      (n=29). Kindling rates and litter sizes for does inseminated with semen stored
      for 48h at 5 degrees C or 15 degrees C and 72h at 5 degrees C were similar
      (P>0.05) to those of the controls; kindling rate dropped following insemination
      with spermatozoa held at 15 degrees C for 72h, though litter size did not. 

PMID- 24852270
TI  - Effects of maternal undernutrition during late pregnancy on the development and
      function of ovine fetal liver.
AB  - This study investigated the effects of maternal undernutrition during late
      pregnancy on the development and function of ovine fetal liver. Eighteen ewes
      with singleton fetuses were allocated to three groups at d 90 of pregnancy:
      Restricted Group 1 (RG1, 0.175MJMEkgBW(-0.75)d(-1), n=6), Restricted Group 2
      (RG2, 0.33MJMEkgBW(-0.75)d(-1), n=6) and a Control Group (CG, ad libitum,
      0.67MJMEkgBW(-0.75)d(-1), n=6). Fetuses were recovered at slaughter on d 140.
      Fetuses in the RG1 group exhibited decreased (P<0.05) liver weight, total
      antioxidant capacity (T-AOC), superoxide dismutase activity (SOD), cholinesterase
      (CHE), total protein (TP), globulin (GLB), and alanine transaminase (ALT). In
      addition, intermediate changes were found in the RG2 fetuses, including decreased
      liver weight, T-AOC and CHE (P<0.05). In contrast, increases in fetal hepatic
      collagen fibers and reticular fibers, glutathione peroxidase (GSH-Px),
      malondialdehyde (MDA), nitric oxide (NO), nitric oxide synthase (NOs), monoamine
      oxidase (MAO), albumin (ALB)/GLB, aspartate transaminase (AST), and AST/ALT were
      found in the RG1 fetuses (P<0.05). The RG2 fetuses had increased fetal hepatic
      collagen fibers, NOs and MAO (P<0.05) relative to the control fetuses. These
      results indicate that impaired fetal hepatic growth, fibrosis, antioxidant
      imbalance and dysfunction were associated with maternal undernutrition. 

PMID- 24852271
TI  - Fundus autofluorescence in Tay-Sachs disease.

PMID- 24852272
TI  - Flocking algorithm for autonomous flying robots.
AB  - Animal swarms displaying a variety of typical flocking patterns would not exist
      without the underlying safe, optimal and stable dynamics of the individuals. The
      emergence of these universal patterns can be efficiently reconstructed with agent
      based models. If we want to reproduce these patterns with artificial systems,
      such as autonomous aerial robots, agent-based models can also be used in their
      control algorithms. However, finding the proper algorithms and thus understanding
      the essential characteristics of the emergent collective behaviour requires
      thorough and realistic modeling of the robot and also the environment. In this
      paper, we first present an abstract mathematical model of an autonomous flying
      robot. The model takes into account several realistic features, such as time
      delay and locality of communication, inaccuracy of the on-board sensors and
      inertial effects. We present two decentralized control algorithms. One is based
      on a simple self-propelled flocking model of animal collective motion, the other
      is a collective target tracking algorithm. Both algorithms contain a viscous
      friction-like term, which aligns the velocities of neighbouring agents parallel
      to each other. We show that this term can be essential for reducing the inherent
      instabilities of such a noisy and delayed realistic system. We discuss simulation
      results on the stability of the control algorithms, and perform real experiments
      to show the applicability of the algorithms on a group of autonomous quadcopters.
      In our case, bio-inspiration works in two ways. On the one hand, the whole idea
      of trying to build and control a swarm of robots comes from the observation that
      birds tend to flock to optimize their behaviour as a group. On the other hand, by
      using a realistic simulation framework and studying the group behaviour of
      autonomous robots we can learn about the major factors influencing the flight of
      bird flocks. 

PMID- 24852273
TI  - New developments in redox chemical delivery systems by means of 1,4
      dihydroquinoline-based targetor: application to galantamine delivery to the
      brain.
AB  - The therapeutic efficiency of palliative treatments of AD, mostly based on
      acetylcholinesterase (AChE) inhibitors, is marred by serious adverse effects due
      to peripheral activity of these AChE inhibitors. In the literature, a redox-based
      chemical delivery system (CDS) has been developed to enhance drugs distribution
      to the brain while reducing peripheral side effects. Herein, we disclose two new
      synthetic strategies for the preparation of 1,4-dihydroquinoline/quinolinium salt
      redox-based systems particularly well designed for brain delivery of drugs
      sensitive to alkylation reactions. These strategies have been applied in the
      present case to the AChE inhibitor galantamine with the aim of alleviating
      adverse effects observed with cholinergic AD treatment. The first strategy is
      based on an intramolecular alkylation reaction as key step, whilst the second
      strategy relies on a useful coupling between galantamine and quinolinium salt key
      intermediate. In the course of this work, polymer-supported reagents and a solid
      phase synthesis approach revealed to be highly helpful to develop this redox
      based galantamine CDS. 

PMID- 24852274
TI  - Synthesis of symmetrically substituted 3,3-dibenzyl-4-hydroxy-3,4-dihydro-1H
      quinolin-2-ones, as novel quinoline derivatives with antibacterial activity.
AB  - A novel series of symmetrically substituted 3,3-dibenzyl-4-hydroxy-3,4-dihydro-1H
      quinolin-2-ones was synthesized and tested as antimicrobials. The minimum
      inhibitory concentration (MIC) values of the most active heterocycles were
      slightly higher than those exhibited by levofloxacin, employed as comparator.
      Structural factors affecting the activity were explored along three
      diversification points, including the substituents of the aromatic rings of the 3
      benzyl moieties, as well as the functionalization of both, the homocyclic ring of
      the heterocycle and the quinolonic nitrogen atom. 6-Chloro and 3,3-bis(4'
      chlorobenzyl) derivatives showed the lower MIC values. Optimally substituted
      heterocycles were synthesized, which exhibited enhanced activity. 

PMID- 24852275
TI  - Design, synthesis and in vitro and in vivo antitumour activity of 3
      benzylideneindolin-2-one derivatives, a novel class of small-molecule inhibitors
      of the MDM2-p53 interaction.
AB  - A novel class of small-molecule inhibitors of MDM2-p53 interaction with a (E)-3
      benzylideneindolin-2-one scaffold was identified using an integrated virtual
      screening strategy that combined both pharmacophore- and structure-based
      approaches. The hit optimisation identified several compounds with more potent
      activity than the hit compound and the positive drug nutlin-3a, especially
      compound 1b, which exhibited both the highest binding affinity to MDM2 (Ki =
      0.093 MUM) and the most potent antiproliferative activity against HCT116 (wild
      type p53) cells (GI50 = 13.42 MUM). Additionally, 1b dose-dependently inhibited
      tumour growth in BALB/c mice bearing CT26 colon carcinoma, with no visible sign
      of toxicity. In summary, compound 1b represents a novel and promising lead
      structure for the development of anticancer drugs as MDM2-p53 interaction
      disruptors. 

PMID- 24852276
TI  - Ferrocenyl and dicobalt hexacarbonyl chromones--new organometallics inducing
      oxidative stress and arresting human cancer cells in G2/M phase.
AB  - The straightforward syntheses of four new ferrocenyl and dicobalt hexacarbonyl
      chromones are presented. The redox behavior of the novel metallo-chromones has
      been examined by cyclic voltammetry (CV), revealing a reversible behavior of the
      ferrocenyl groups, while the dicobalt hexacarbonyl derivatives show irreversible
      oxidation. The anticancer activity of the products has been evaluated against
      hepatocellular carcinoma (Hep G2), ER+ (MCF-7) and ER- (MDA-MB-231) breast
      adenocarcinoma, and leukemic (CCRF-CEM) human cancer cell lines. The mechanism of
      action for the most active complexes has been investigated and it seems to
      involve oxidative stress and apoptosis induction. Moreover, the results show that
      the investigated metallo-chromones generate damage to DNA and arrest the cell
      cycle in G2/M phase. 

PMID- 24852278
TI  - Three new cembranoid-type diterpenes from Red Sea soft coral Sarcophyton glaucum:
      isolation and antiproliferative activity against HepG2 cells.
AB  - Three new cembranoids: sarcophytolol (1), sarcophytolide B (2), and
      sarcophytolide C (3), along with three known metabolites: 10(14)aromadendrene
      (4), deoxosarcophine (5), and sarcophine (6) were obtained from the soft bodied
      coral Sarcophyton glaucum. The structures were determined based on spectroscopic
      measurements (NMR, UV, IR and MS). Compounds 1, 3, and 4 had similar significant
      cytotoxic effects towards HepG2 (Human hepatocellular liver carcinoma; IC50 = 20
      MUM). 2 and 3 showed activity against MCF-7 (Human breast adenocarcinoma; IC50 25
      +/- 0.0164 and 29 +/- 0.030 MUM, respectively). Finally, 4 showed potent activity
      towards PC-3 (Prostate cancer; IC50 9.3 +/- 0.164 MUM). The antiproliferative
      activity of 1, 3 and 4, can be attributed, at least partly, to their ability to
      induce cellular apoptosis. 

PMID- 24852277
TI  - Synthesis of novel 1,2,3-triazole derivatives of isoniazid and their in vitro and
      in vivo antimycobacterial activity evaluation.
AB  - We report herein the synthesis and antimycobacterial activity of 1,2,3-triazole
      derivatives of isoniazid. Most of the compounds exhibited potent activity against
      Mycobacterium tuberculosis H37Rv strain with MIC99 values ranging from 0.195 to
      1.56 MUM in vitro. One compound showed better in vitro activity than the
      reference, whereas five compounds were equally potent to the reference compound
      isoniazid. The cytotoxicity of these compounds was studied against THP-1 cell
      line and no toxicity was observed even at 50 MUM concentration. The compound with
      most potent in vitro activity was evaluated for in vivo in murine model of
      tuberculosis and significantly reduced bacillary load in both lungs and spleen at
      10 weeks post-treatment. However this clearance effect was more pronounced in the
      case of spleen. Molecular docking and molecular dynamics simulations have been
      performed using two targets 2IDZ 1 (wild type Enoyl-acyl-carrier-protein
      reductase) and 4DQU 2 (mutant type Enoyl-acyl-carrier-protein reductase) to study
      the binding orientation and stability of the compound 47. Docking studies proved
      compound 47 fit well into the binding pocket of both the targets. Molecular
      dynamic simulations concluded that the highest active compound 47 in complex with
      4DQU was more stable when compared to the 2IDZ. We believe that further
      optimization of these molecules may lead to potent anti-tubercular agents. 

PMID- 24852279
TI  - Polyisoprenylated methylated protein methyl esterase: a putative biomarker and
      therapeutic target for pancreatic cancer.
AB  - Pancreatic cancer is the most deadly neoplasm with a 5-year survival rate of less
      than 6%. Over 90% of cases harbor K-Ras mutations, which are the most challenging
      to treat due to lack of effective therapies. Here, we reveal that
      polyisoprenylated methylated protein methyl esterase (PMPMEase) is overexpressed
      in 93% of pancreatic ductal adenocarcinoma. We further present polyisoprenylated
      cysteinyl amide inhibitors (PCAIs) as novel compounds designed with structural
      elements for optimal in vivo activities and selective disruption of
      polyisoprenylation-mediated protein functions. The PCAIs inhibited PMPMEase with
      Ki values ranging from 3.7 to 20 MUM. The 48 h EC50 values for pancreatic cancer
      Mia PaCa-2 and BxPC-3 cell lines were as low as 1.9 MUM while salirasib and
      farnesylthiosalicylamide were ineffective at 20 MUM. The PCAIs thus have the
      potential to serve as effective therapies for pancreatic and other cancers with
      hyperactive growth signaling pathways mediated by Ras and related G-proteins. 

PMID- 24852280
TI  - A new convenient synthetic method and preliminary pharmacological
      characterization of triazinediones as prokineticin receptor antagonists.
AB  - A new efficient synthetic method to obtain prokineticin receptor antagonists
      based on the triazinedione scaffold is described. In this procedure the overall
      yield improves from 13% to about 54%, essentially for two factors: 1) N
      (chlorocarbonyl) isocyanate is no more used, it represents the yield limiting
      step with an average yield not exceeding 30%. 2) The Mitsunobu reaction is not
      involved in the new synthetic scheme avoiding the use of time and solvent
      consuming column chromatography. All synthesized triazinediones were preliminary
      pharmacologically screened in vivo for their ability to reduce the Bv8-induced
      thermal hyperalgesia. In this assay all compounds displayed EC50 values in the
      picomolar-subpicomolar range, some triazinediones containing a 4-halogen
      substituted benzyl group in position 5 showed the best activity. The analogues
      containing a 4-fluorine atom (PC-7) and a 4-bromobenzyl group (PC-25) resulted 10
      times more potent than the reference PC-1 that bears a 4-ethylbenzyl group. While
      the 4-trifluoromethylbenzyl substituted analog (PC-27) was 100 times more potent
      as compared to PC1. 

PMID- 24852282
TI  - Quality improvement for the ambulatory surgery center.

PMID- 24852281
TI  - Synthesis and antiproliferative effect of novel 4-thiazolidinone-, pyridine- and
      piperazine-based conjugates on human leukemic cells.
AB  - The present work reveals the synthesis and antiproliferative effect of a series
      of 2, 3 disubstituted 4-thiazolidinone analogues on human leukemic cells. The
      chemical structures of newly synthesized compounds were confirmed by IR, (1)H
      NMR, (13)C NMR and mass spectral analysis. Compound methyl 3-methoxy-4-(4-oxo-3
      (5-(piperazin-1-yl)pyridin-2-yl)thiazolidin-2-yl)benzoate (5) displayed potent
      activity (IC509.71, 15.24 and 19.29 MUM) against Nalm6, K562, Jurkat cells. Cell
      cycle analysis and mitochondrial membrane potential further confirmed that
      compound 5 is cytotoxic and able to induce cell death. 

PMID- 24852283
TI  - Imaging adherent cells in the microfluidic channel hidden by flowing RBCs as
      occluding objects by a holographic method.
AB  - Imaging through turbid media is a challenging topic. A liquid is considered
      turbid when dispersed particles provoke strong light scattering, thus destroying
      the image formation by any standard optical system. Generally, colloidal
      solutions belong to the class of turbid media since dispersed particles have
      dimensions ranging between 0.2 MUm and 2 MUm. However, in microfluidics, another
      relevant issue has to be considered in the case of flowing liquid made of a
      multitude of occluding objects, e.g. red blood cells (RBCs) flowing in veins. In
      such a case instead of severe scattering processes unpredictable phase delays
      occur resulting in a wavefront distortion, thus disturbing or even hindering the
      image formation of objects behind such obstructing layer. In fact RBCs can be
      considered to be thin transparent phase objects. Here we show that sharp
      amplitude imaging and phase-contrast mapping of cells hidden behind biological
      occluding objects, namely RBCs, is possible in harsh noise conditions and with a
      large field-of view by Multi-Look Digital Holography microscopy (ML-DH).
      Noteworthy, we demonstrate that ML-DH benefits from the presence of the RBCs,
      providing enhancement in terms of numerical resolution and noise suppression thus
      obtaining images whose quality is higher than the quality achievable in the case
      of a liquid without occlusive objects. 

PMID- 24852284
TI  - Effects of Lactobacillus paracasei CNCM I-4034, Bifidobacterium breve CNCM I-4035
      and Lactobacillus rhamnosus CNCM I-4036 on hepatic steatosis in Zucker rats.
AB  - We have previously described the safety and immunomodulatory effects of
      Lactobacillus paracasei CNCM I-4034, Bifidobacterium breve CNCM I-4035 and
      Lactobacillus rhamnosus CNCM I-4036 in healthy volunteers. The scope of this work
      was to evaluate the effects of these probiotic strains on the hepatic steatosis
      of obese rats. We used the Zucker rat as a genetic model of obesity. Zucker
      Lepr(fa/fa) rats received one of three probiotic strains, a mixture of L.
      paracasei CNCM I-4034 and B. breve CNCM I-4035, or a placebo for 30 days. An
      additional group of Zucker-lean+/fa rats received a placebo for 30 days. No
      alterations in intestinal histology, in the epithelial, lamina propria, muscular
      layers of the ileal or colonic mucosa, or the submucosae, were observed in any of
      the experimental groups. Triacylglycerol content decreased in the liver of Zucker
      Lepr(fa/fa) rats that were fed L. rhamnosus, B. breve, or the mixture of B. breve
      and L. paracasei. Likewise, the area corresponding to neutral lipids was
      significantly smaller in the liver of all four groups of Zucker-Lepr(fa/fa) rats
      that received probiotics than in rats fed the placebo. Zucker-Lepr(fa/fa) rats
      exhibited significantly greater serum LPS levels than Zucker-lean+/fa rats upon
      administration of placebo for 30 days. In contrast, all four groups of obese
      Zucker-Lepr(fa/fa) rats that received LAB strains exhibited serum LPS
      concentrations similar to those of Zucker-lean+/fa rats. Serum TNF-alpha levels
      decreased in the Zucker-Lepr(fa/fa) rats that received B. breve, L. rhamnosus, or
      the mixture, whereas L. paracasei feeding decreased IL-6 levels in the serum of
      Zucker-Lepr(fa/fa) rats. In conclusion, the probiotic strains reduced hepatic
      steatosis in part by lowering serum LPS, and had an anti-inflammatory effect in
      obese Zucker rats.

PMID- 24852286
TI  - Prevalence of orthorexia nervosa among ashtanga yoga practitioners: a pilot
      study.
AB  - PURPOSE: Orthorexia nervosa (ON, i.e., fixation on righteous eating) is a poorly
      defined disordered eating behavior that results from a pathological obsession
      with food, its purported nutritional value, composition, origin, etc. METHODS: We
      investigated the prevalence of ON in a local ashtanga yoga community, by using a
      validated questionnaire (ORTO-15) that sets a threshold of ON diagnosis at <=40.
      RESULTS: Among the 136 respondents, the mean ORTO-15 score (which was normally
      distributed) was 35.27 +/- 3.69, i.e., 86 % of respondents had an ORTO-15 score
      lower than 40 and no significant association with age or BMI was recorded. When
      we analyzed the differential distribution of orthorexia in our cohort, we
      recorded an association of ORTO-15 score and vegetarianism, i.e., the ORTO-15
      score was lower among vegetarians. CONCLUSIONS: The results of this pilot study
      should suggest ashtanga yoga teachers to avoid excessive reference to a healthy
      diet, which is natural component of yoga practice.

PMID- 24852285
TI  - Assessment of blood-brain barrier function and the neuroinflammatory response in
      the rat brain by using cerebral open flow microperfusion (cOFM).
AB  - Blood-brain barrier (BBB) impairment in systemic inflammation leads to
      neuroinflammation. Several factors including cytokines, chemokines and signal
      transduction molecules are implicated in BBB dysfunction in response to systemic
      inflammation. Here, we have adopted a novel in vivo technique; namely, cerebral
      open flow microperfusion (cOFM), to perform time-dependent cytokine analysis (TNF
      alpha, IL-6 and IL-10) in the frontal cortex of the rat brain in response to a
      single peripheral administration of lipopolysaccharide (LPS). In parallel, we
      monitored BBB function using sodium fluorescein as low molecular weight reporter
      in the cOFM sample. In response to the systemic LPS administration, we observed a
      rapid increase of TNF-alpha in the serum and brain, which coincides with the BBB
      disruption. Brain IL-6 and IL-10 synthesis was delayed by approximately 1 h. Our
      data demonstrate that cOFM can be used to monitor changes in brain cytokine
      levels and BBB disruption in a rat sepsis model. 

PMID- 24852287
TI  - Gadolinium contrast agents for CNS imaging: current concepts and clinical
      evidence.
AB  - SUMMARY: The aim of this article was to review the properties of the various
      gadolinium-based contrast agents used for CNS imaging along with the clinical
      evidence and published data that highlight the impact these different properties
      can have on diagnostic performance. In addition, approaches to optimizing image
      acquisition that take into account the different properties of specific
      gadolinium-based contrast agents and an extensive review of the safety profiles
      of the various agents are presented.

PMID- 24852288
TI  - Intracranial aneurysmal pulsatility as a new individual criterion for rupture
      risk evaluation: biomechanical and numeric approach (IRRAs Project).
AB  - BACKGROUND AND PURPOSE: The present study follows an experimental work based on
      the characterization of the biomechanical behavior of the aneurysmal wall and a
      numerical study where a significant difference in term of volume variation
      between ruptured and unruptured aneurysm was observed in a specific case. Our
      study was designed to highlight by means of numeric simulations the correlation
      between aneurysm sac pulsatility and the risk of rupture through the mechanical
      properties of the wall. MATERIALS AND METHODS: In accordance with previous work
      suggesting a correlation between the risk of rupture and the material properties
      of cerebral aneurysms, 12 fluid-structure interaction computations were performed
      on 12 "patient-specific" cases, corresponding to typical shapes and locations of
      cerebral aneurysms. The variations of the aneurysmal volume during the cardiac
      cycle (DeltaV) are compared by using wall material characteristics of either
      degraded or nondegraded tissues. RESULTS: Aneurysms were located on 6 different
      arteries: middle cerebral artery (4), anterior cerebral artery (3), internal
      carotid artery (1), vertebral artery (1), ophthalmic artery (1), and basilar
      artery (1). Aneurysms presented different shapes (uniform or multilobulated) and
      diastolic volumes (from 18 to 392 mm3). The pulsatility (DeltaV/V) was
      significantly larger for a soft aneurysmal material (average of 26%) than for a
      stiff material (average of 4%). The difference between DeltaV, for each
      condition, was statistically significant: P=.005. CONCLUSIONS: The difference in
      aneurysmal pulsatility as highlighted in this work might be a relevant patient
      specific predictor of aneurysm risk of rupture.

PMID- 24852289
TI  - MR myelography for identification of spinal CSF leak in spontaneous intracranial
      hypotension.
AB  - BACKGROUND AND PURPOSE: CT myelography has historically been the test of choice
      for localization of CSF fistula in patients with spontaneous intracranial
      hypotension. This study evaluates the additional benefits of intrathecal
      gadolinium MR myelography in the detection of CSF leak. MATERIALS AND METHODS: We
      performed a retrospective review of patients with spontaneous intracranial
      hypotension who underwent CT myelography followed by intrathecal gadolinium MR
      myelography. All patients received intrathecal iodine and off-label gadolinium
      based contrast followed by immediate CT myelography and subsequent intrathecal
      gadolinium MR myelography with multiplanar T1 fat-suppressed sequences. CT
      myelography and intrathecal gadolinium MR myelography images were reviewed by an
      experienced neuroradiologist to determine the presence of CSF leak. Patient
      records were reviewed for demographic data and adverse events following the
      procedure. RESULTS: Twenty-four patients met both imaging and clinical criteria
      for spontaneous intracranial hypotension and underwent CT myelography followed by
      intrathecal gadolinium MR myelography. In 3/24 patients (13%), a CSF leak was
      demonstrated on both CT myelography and intrathecal gadolinium MR myelography,
      and in 9/24 patients (38%), a CSF leak was seen on intrathecal gadolinium MR
      myelography (P = .011). Four of 6 leaks identified independently by intrathecal
      gadolinium MR myelography related to meningeal diverticula. CT myelography did
      not identify any leaks independently. There were no reported adverse events.
      CONCLUSIONS: Present data demonstrate a higher rate of leak detection with
      intrathecal gadolinium MR myelography when investigating CSF leaks in our cohort
      of patients with spontaneous intracranial hypotension. Although intrathecal
      gadolinium is an FDA off-label use, all patients tolerated the medication without
      evidence of complications. Our data suggest that intrathecal gadolinium MR
      myelography is a well-tolerated examination with significant benefit in the
      evaluation of CSF leak, particularly for patients with leak related to meningeal
      diverticula.

PMID- 24852290
TI  - Direct visualization of anatomic subfields within the superior aspect of the
      human lateral thalamus by MRI at 7T.
AB  - BACKGROUND AND PURPOSE: The morphology of the human thalamus shows high
      interindividual variability. Therefore, direct visualization of landmarks within
      the thalamus is essential for an improved definition of electrode positions for
      deep brain stimulation. The aim of this study was to provide anatomic detail in
      the thalamus by using inversion recovery TSE imaging at 7T. MATERIALS AND
      METHODS: The MR imaging protocol was optimized on 1 healthy subject to segment
      thalamic nuclei from one another. Final images, acquired with 0.5(2)-mm2 in-plane
      resolution and 3-mm section thickness, were compared with stereotactic brain
      atlases to assign visualized details to known anatomy. The robustness of the
      visualization of thalamic nuclei was assessed with 4 healthy subjects at lower
      image resolution. RESULTS: Thalamic subfields were successfully delineated in the
      dorsal aspect of the lateral thalamus. T1-weighting was essential. MR images had
      an appearance very similar to that of myelin-stained sections seen in brain
      atlases. Visualized intrathalamic structures were, among others, the lamella
      medialis, the external medullary lamina, the reticulatum thalami, the nucleus
      centre median, the boundary between the nuclei dorso-oralis internus and
      externus, and the boundary between the nuclei dorso-oralis internus and
      zentrolateralis intermedius internus. CONCLUSIONS: Inversion recovery-prepared
      TSE imaging at 7T has a high potential to reveal fine anatomic detail in the
      thalamus, which may be helpful in enhancing the planning of stereotactic
      neurosurgery in the future.

PMID- 24852291
TI  - MRI-based radiologic scoring system for extent of brain injury in children with
      hemiplegia.
AB  - BACKGROUND AND PURPOSE: Brain MR imaging is recommended in children with cerebral
      palsy. Descriptions of MR imaging findings lack uniformity, due to the absence of
      a validated quantitative approach. We developed a quantitative scoring method for
      brain injury based on anatomic MR imaging and examined the reliability and
      validity in correlation to motor function in children with hemiplegia. MATERIALS
      AND METHODS: Twenty-seven children with hemiplegia underwent MR imaging (T1, T2
      weighted sequences, DTI) and motor assessment (Manual Ability Classification
      System, Gross Motor Functional Classification System, Assisting Hand Assessment,
      Jebsen Taylor Test of Hand Function, and Children's Hand Experience
      Questionnaire). A scoring system devised in our center was applied to all scans.
      Radiologic score covered 4 domains: number of affected lobes, volume and type of
      white matter injury, extent of gray matter damage, and major white matter tract
      injury. Inter- and intrarater reliability was evaluated and the relationship
      between radiologic score and motor assessments determined. RESULTS: Mean total
      radiologic score was 11.3 +/- 4.5 (range 4-18). Good inter- (rho = 0.909, P <
      .001) and intrarater (rho = 0.926, P = < .001) reliability was demonstrated.
      Radiologic score correlated significantly with manual ability classification
      systems (rho = 0.708, P < .001), and with motor assessments (assisting hand
      assessment [rho = -0.753, P < .001]; Jebsen Taylor test of hand function [rho =
      0. 766, P < .001]; children's hand experience questionnaire [rho = -0. 716, P <
      .001]), as well as with DTI parameters. CONCLUSIONS: We present a novel MR
      imaging-based scoring system that demonstrated high inter- and intrarater
      reliability and significant associations with manual ability classification
      systems and motor evaluations. This score provides a standardized radiologic
      assessment of brain injury extent in hemiplegic patients with predominantly
      unilateral injury, allowing comparison between groups, and providing an
      additional tool for counseling families.

PMID- 24852292
TI  - Selectivity in genetic association with sub-classified migraine in women.
AB  - Migraine can be sub-classified not only according to presence of migraine aura
      (MA) or absence of migraine aura (MO), but also by additional features
      accompanying migraine attacks, e.g. photophobia, phonophobia, nausea, etc. all of
      which are formally recognized by the International Classification of Headache
      Disorders. It remains unclear how aura status and the other migraine features may
      be related to underlying migraine pathophysiology. Recent genome-wide association
      studies (GWAS) have identified 12 independent loci at which single nucleotide
      polymorphisms (SNPs) are associated with migraine. Using a likelihood framework,
      we explored the selective association of these SNPs with migraine, sub-classified
      according to aura status and the other features in a large population-based
      cohort of women including 3,003 active migraineurs and 18,108 free of migraine.
      Five loci met stringent significance for association with migraine, among which
      four were selective for sub-classified migraine, including rs11172113 (LRP1) for
      MO. The number of loci associated with migraine increased to 11 at suggestive
      significance thresholds, including five additional selective associations for MO
      but none for MA. No two SNPs showed similar patterns of selective association
      with migraine characteristics. At one extreme, SNPs rs6790925 (near TGFBR2) and
      rs2274316 (MEF2D) were not associated with migraine overall, MA, or MO but were
      selective for migraine sub-classified by the presence of one or more of the
      additional migraine features. In contrast, SNP rs7577262 (TRPM8) was associated
      with migraine overall and showed little or no selectivity for any of the migraine
      characteristics. The results emphasize the multivalent nature of migraine
      pathophysiology and suggest that a complete understanding of the genetic
      influence on migraine may benefit from analyses that stratify migraine according
      to both aura status and the additional diagnostic features used for clinical
      characterization of migraine. 

PMID- 24852293
TI  - Mutations in SETD2 cause a novel overgrowth condition.
AB  - BACKGROUND: Overgrowth conditions are a heterogeneous group of disorders
      characterised by increased growth and variable features, including macrocephaly,
      distinctive facial appearance and various degrees of learning difficulties and
      intellectual disability. Among them, Sotos and Weaver syndromes are clinically
      well defined and due to heterozygous mutations in NSD1 and EZH2, respectively.
      NSD1 and EZH2 are both histone-modifying enzymes. These two epigenetic writers
      catalyse two specific post-translational modifications of histones: methylation
      of histone 3 lysine 36 (H3K36) and lysine 27 (H3K27). We postulated that
      mutations in writers of these two chromatin marks could cause overgrowth
      conditions, resembling Sotos or Weaver syndromes, in patients with no NSD1 or
      EZH2 abnormalities. METHODS: We analysed the coding sequences of 14 H3K27
      methylation-related genes and eight H3K36 methylation-related genes using a
      targeted next-generation sequencing approach in three Sotos, 11 'Sotos-like' and
      two Weaver syndrome patients. RESULTS: We identified two heterozygous mutations
      in the SETD2 gene in two patients with 'Sotos-like' syndrome: one missense
      p.Leu1815Trp de novo mutation in a boy and one nonsense p.Gln274* mutation in an
      adopted girl. SETD2 is non-redundantly responsible for H3K36 trimethylation. The
      two probands shared similar clinical features, including postnatal overgrowth,
      macrocephaly, obesity, speech delay and advanced carpal ossification.
      CONCLUSIONS: Our results illustrate the power of targeted next-generation
      sequencing to identify rare disease-causing variants. We provide a compelling
      argument for Sotos and Sotos-like syndromes as epigenetic diseases caused by loss
      of-function mutations of epigenetic writers of the H3K36 histone mark.

PMID- 24852295
TI  - The prognostic significance of inspiratory capacity in pulmonary arterial
      hypertension.
AB  - BACKGROUND: Patients with pulmonary arterial hypertension (PAH) present with an
      altered inspiratory capacity (IC) reflecting dynamic hyperinflation (DH) that
      leads to mechanical constraints and excessive ventilatory demand, particularly
      during exercise, resulting in exertional dyspnea. OBJECTIVES: Assessment of the
      long-term consequences of altered IC and DH in PAH. METHODS: 50 patients with
      newly diagnosed PAH were prospectively recruited. All patients were assessed by
      means of right heart catheterization, 6-min walking distance (6MWD) test, lung
      function and cardiopulmonary exercise testing, including the assessment of IC.
      RESULTS: 37 patients with idiopathic PAH and 13 patients with conditions
      associated with PAH (29 female; mean age 51.6 +/- 15.1 years; World Health
      Organization, WHO class, 2.7 +/- 0.6) presented with a mean pulmonary arterial
      pressure of 42.8 +/- 15.9 mm Hg and pulmonary vascular resistance (PVR) of 737.2
      +/- 592.8 dyn*s/cm(5). The mean IC at rest was 87.2 +/- 17.3% pred. Kaplan-Meier
      analysis revealed that patients with an IC at rest >89% pred. had a significantly
      better 5-year survival than those with lower values (94.1 vs. 75.1%; log-rank p =
      0.036). Univariate analysis identified IC at rest (% pred.) as a predictor of
      survival with a hazard ratio (HR) of 5.05 (95% confidence interval, CI, 0.97
      26.24, p = 0.054). In multivariate analysis including PVR, WHO class, 6MWD and
      peak oxygen uptake as covariates, IC at rest remained an independent predictor of
      survival (HR: 8.06, 95% CI 0.92-70.34; p = 0.059). DH expressed as DeltaIC or
      static hyperinflation expressed as IC/total lung capacity at rest revealed no
      prognostic significance. CONCLUSION: In patients with PAH, IC at rest is of
      prognostic significance at the time of diagnosis.

PMID- 24852294
TI  - Integrative functional genomics of hepatitis C virus infection identifies host
      dependencies in complete viral replication cycle.
AB  - Recent functional genomics studies including genome-wide small interfering RNA
      (siRNA) screens demonstrated that hepatitis C virus (HCV) exploits an extensive
      network of host factors for productive infection and propagation. How these co
      opted host functions interact with various steps of HCV replication cycle and
      exert pro- or antiviral effects on HCV infection remains largely undefined. Here
      we present an unbiased and systematic strategy to functionally interrogate HCV
      host dependencies uncovered from our previous infectious HCV (HCVcc) siRNA
      screen. Applying functional genomics approaches and various in vitro HCV model
      systems, including HCV pseudoparticles (HCVpp), single-cycle infectious particles
      (HCVsc), subgenomic replicons, and HCV cell culture systems (HCVcc), we
      identified and characterized novel host factors or pathways required for each
      individual step of the HCV replication cycle. Particularly, we uncovered multiple
      HCV entry factors, including E-cadherin, choline kinase alpha, NADPH oxidase
      CYBA, Rho GTPase RAC1 and SMAD family member 6. We also demonstrated that guanine
      nucleotide binding protein GNB2L1, E2 ubiquitin-conjugating enzyme UBE2J1, and 39
      other host factors are required for HCV RNA replication, while the
      deubiquitinating enzyme USP11 and multiple other cellular genes are specifically
      involved in HCV IRES-mediated translation. Families of antiviral factors that
      target HCV replication or translation were also identified. In addition, various
      virologic assays validated that 66 host factors are involved in HCV assembly or
      secretion. These genes included insulin-degrading enzyme (IDE), a proviral
      factor, and N-Myc down regulated Gene 1 (NDRG1), an antiviral factor.
      Bioinformatics meta-analyses of our results integrated with literature mining of
      previously published HCV host factors allows the construction of an extensive
      roadmap of cellular networks and pathways involved in the complete HCV
      replication cycle. This comprehensive study of HCV host dependencies yields novel
      insights into viral infection, pathogenesis and potential therapeutic targets. 

PMID- 24852296
TI  - SMAD3 is associated with the total burden of radiographic osteoarthritis: the
      Chingford study.
AB  - BACKGROUND: A newly-described syndrome called Aneurysm-Osteoarthritis Syndrome
      (AOS) was recently reported. AOS presents with early onset osteoarthritis (OA) in
      multiple joints, together with aneurysms in major arteries, and is caused by rare
      mutations in SMAD3. Because of the similarity of AOS to idiopathic generalized OA
      (GOA), we hypothesized that SMAD3 is also associated with GOA and tested the
      hypothesis in a population-based cohort. METHODS: Study participants were derived
      from the Chingford study. Kellgren-Lawrence (KL) grades and the individual
      features of osteophytes and joint space narrowing (JSN) were scored from
      radiographs of hands, knees, hips, and lumbar spines. The total KL score,
      osteophyte score, and JSN score were calculated and used as indicators of the
      total burden of radiographic OA. Forty-one common SNPs within SMAD3 were
      genotyped using the Illumina HumanHap610Q array. Linear regression modelling was
      used to test the association between the total KL score, osteophyte score, and
      JSN score and each of the 41 SNPs, with adjustment for patient age and BMI.
      Permutation testing was used to control the false positive rate. RESULTS: A total
      of 609 individuals were included in the analysis. All were Caucasian females with
      a mean age of 60.9+/-5.8. We found that rs3825977, with a minor allele (T)
      frequency of 20%, in the last intron of SMAD3, was significantly associated with
      total KL score (beta = 0.14, Ppermutation = 0.002). This association was stronger
      for the total JSN score (beta = 0.19, Ppermutation = 0.002) than for total
      osteophyte score (beta = 0.11, Ppermutation = 0.02). The T allele is associated
      with a 1.47-fold increased odds for people with 5 or more joints to be affected
      by radiographic OA (Ppermutation = 0.046). CONCLUSION: We found that SMAD3 is
      significantly associated with the total burden of radiographic OA. Further
      studies are required to reveal the mechanism of the association.

PMID- 24852297
TI  - Why women choose to give birth at home: a situational analysis from urban slums
      of Delhi.
AB  - OBJECTIVES: Increasing institutional births is an important strategy for
      attaining Millennium Development Goal -5. However, rapid growth of low income and
      migrant populations in urban settings in low-income and middle-income countries,
      including India, presents unique challenges for programmes to improve utilisation
      of institutional care. Better understanding of the factors influencing home or
      institutional birth among the urban poor is urgently needed to enhance programme
      impact. To measure the prevalence of home and institutional births in an urban
      slum population and identify factors influencing these events. DESIGN: Cross
      sectional survey using quantitative and qualitative methods. SETTING: Urban poor
      settlements in Delhi, India. PARTICIPANTS: A house-to-house survey was conducted
      of all households in three slum clusters in north-east Delhi (n=32 034
      individuals). Data on birthing place and sociodemographic characteristics were
      collected using structured questionnaires (n=6092 households). Detailed
      information on pregnancy and postnatal care was obtained from women who gave
      birth in the past 3 months (n=160). Focus group discussions and in-depth
      interviews were conducted with stakeholders from the community and healthcare
      facilities. RESULTS: Of the 824 women who gave birth in the previous year, 53%
      (95% CI 49.7 to 56.6) had given birth at home. In adjusted analyses, multiparity,
      low literacy and migrant status were independently predictive of home births.
      Fear of hospitals (36%), comfort of home (20.7%) and lack of social support for
      child care (12.2%) emerged as the primary reasons for home births. CONCLUSIONS:
      Home births are frequent among the urban poor. This study highlights the urgent
      need for improvements in the quality and hospitality of client services and need
      for family support as the key modifiable factors affecting over two-thirds of
      this population. These findings should inform the design of strategies to promote
      institutional births.

PMID- 24852298
TI  - Effects of the expansion of doctors' offices adjacent to private pharmacies in
      Mexico: secondary data analysis of a national survey.
AB  - OBJECTIVES: To compare the sociodemographic characteristics, reasons for
      attending, perception of quality and associated out-of-pocket (OOP) expenditures
      of doctors' offices adjacent to private pharmacies (DAPPs) users with users of
      Social Security (SS), Ministry of Health (MoH), private doctor's offices
      independent from pharmacies and non-users. SETTING: Secondary data analysis of
      the 2012 National Survey of Health and Nutrition of Mexico. PARTICIPANTS: The
      study population comprised 25 852 individuals identified as having had a health
      problem 15 days before the survey, and a random sample of 12 799 ambulatory
      health service users. OUTCOME MEASURES: Sociodemographic characteristics, reasons
      for attending healthcare services, perception of quality and associated OOP
      expenditures. RESULTS: The distribution of users was as follows: DAPPs (9.2%), SS
      (16.1%), MoH (20.9%), private providers (15.4%) and non-users (38.5%); 65% of
      DAPP users were affiliated with a public institution (MoH 35%, SS 30%) and 35%
      reported not having health coverage. DAPP users considered the services
      inexpensive, convenient and with a short waiting time, yet they received >=3
      medications more often (67.2%, 95% CI 64.2% to 70.1%) than users of private
      doctors (55.7%, 95% CI 52.5% to 58.6%) and public institutions (SS 53.8%, 95% CI
      51.6% to 55.9%; MoH 44.7%, 95% CI 42.5% to 47.0%). The probability of spending on
      consultations (88%, 95% CI 86% to 89%) and on medicines (97%, 95% CI 96% to 98%)
      was much higher for DAPP users when compared with SS (2%, 95% CI 2% to 3% and
      12%, 95% CI 11% to 14%, respectively) and MoH users (11%, 95% CI 9% to 12% and
      32%, 95% CI 30% to 34%, respectively). CONCLUSIONS: DAPPs counteract current
      financial protection policies since a significant percentage of their users were
      affiliated with a public institution, reported higher OOP spending and higher
      number of medicines prescribed than users of other providers. The
      overprescription should prompt studies to learn about DAPPs' quality of care,
      which may arise from the conflict of interest implicit in the linkage of
      prescribing and dispensing processes.

PMID- 24852299
TI  - Ethnicity and the association between anthropometric indices of obesity and
      cardiovascular risk in women: a cross-sectional study.
AB  - OBJECTIVES: The objectives of this study were to determine whether the cross
      sectional associations between anthropometric obesity measures, body mass index
      (BMI), waist circumference (WC) and waist-to-hip ratio (WHR), and calculated 10
      year cardiovascular disease (CVD) risk using the Framingham and general CVD risk
      score models, are the same for women of Australian, UK and Ireland, North
      European, South European and Asian descent. This study would investigate which
      anthropometric obesity measure is most predictive at identifying women at
      increased CVD risk in each ethnic group. DESIGN: Cross-sectional data from the
      National Heart Foundation Risk Factor Prevalence Study. SETTING: Population-based
      survey in Australia. PARTICIPANTS: 4354 women aged 20-69 years with no history of
      heart disease, diabetes or stroke. Most participants were of Australian, UK and
      Ireland, North European, South European or Asian descent (97%). OUTCOME MEASURES:
      Anthropometric obesity measures that demonstrated stronger predictive ability of
      identifying women at increased CVD risk and likelihood of being above the
      promulgated treatment thresholds of various risk score models. RESULTS: Central
      obesity measures, WC and WHR, were better predictors of cardiovascular risk. WHR
      reported a stronger predictive ability than WC and BMI in Caucasian women. In
      Northern European women, BMI was a better indicator of risk using the general CVD
      (10% threshold) and Framingham (20% threshold) risk score models. WC was the most
      predictive of cardiovascular risk among Asian women. CONCLUSIONS: Ethnicity
      should be incorporated into CVD assessment. The same anthropometric obesity
      measure cannot be used across all ethnic groups. Ethnic-specific CVD prevention
      and treatment strategies need to be further developed.

PMID- 24852300
TI  - Facilitators and barriers to quality of care in maternal, newborn and child
      health: a global situational analysis through metareview.
AB  - OBJECTIVE: Conduct a global situational analysis to identify the current
      facilitators and barriers to improving quality of care (QoC) for pregnant women,
      newborns and children. STUDY DESIGN: Metareview of published and unpublished
      systematic reviews and meta-analyses conducted between January 2000 and March
      2013 in any language. Assessment of Multiple Systematic Reviews (AMSTAR) is used
      to assess the methodological quality of systematic reviews. SETTINGS: Health
      systems of all countries. Study outcome: QoC measured using surrogate indicators-
      effective, efficient, accessible, acceptable/patient centred, equitable and safe.
      ANALYSIS: Conducted in two phases (1) qualitative synthesis of extracted data to
      identify and group the facilitators and barriers to improving QoC, for each of
      the three population groups, into the six domains of WHO's framework and explore
      new domains and (2) an analysis grid to map the common facilitators and barriers.
      RESULTS: We included 98 systematic reviews with 110 interventions to improve QoC
      from countries globally. The facilitators and barriers identified fitted the six
      domains of WHO's framework--information, patient-population engagement,
      leadership, regulations and standards, organisational capacity and models of
      care. Two new domains, 'communication' and 'satisfaction', were generated.
      Facilitators included active and regular interpersonal communication between
      users and providers; respect, confidentiality, comfort and support during care
      provision; engaging users in decision-making; continuity of care and effective
      audit and feedback mechanisms. Key barriers identified were language barriers in
      information and communication; power difference between users and providers;
      health systems not accounting for user satisfaction; variable standards of
      implementation of standard guidelines; shortage of resources in health facilities
      and lack of studies assessing the role of leadership in improving QoC. These were
      common across the three population groups. CONCLUSIONS: The barriers to good
      quality healthcare are common for pregnant women, newborns and children; thus,
      interventions targeted to address them will have uniform beneficial effects.
      Adopting the identified facilitators would help countries strengthen their health
      systems and ensure high-quality care for all.

PMID- 24852301
TI  - PROSPECTIV-a pilot trial of a nurse-led psychoeducational intervention delivered
      in primary care to prostate cancer survivors: study protocol for a randomised
      controlled trial.
AB  - BACKGROUND: Prostate cancer survivors can experience physical, sexual,
      psychological and emotional problems, and there is evidence that current follow
      up practices fail to meet these men's needs. Studies show that secondary and
      primary care physicians see a greater role for primary care in delivering follow
      up, and that primary care-led follow-up is acceptable to men with prostate
      cancer. METHODS AND ANALYSIS: A two-phase study with target population being men
      who are 9-24 months from diagnosis. Phase 1 questionnaire aims to recruit 300 men
      and measure prostate-related quality of life and unmet needs. Men experiencing
      problems with urinary, bowel, sexual or hormonal function will be eligible for
      phase 2, a pilot trial of a primary care nurse-led psychoeducational
      intervention. Consenting eligible participants will be randomised either to
      intervention plus usual care, or usual care alone (40 men in each arm). The
      intervention, based on a self-management approach, underpinned by Bandura's
      Social Cognitive Theory, will provide advice and support tailored to these men's
      needs and address any problems they are experiencing. Telephone follow-up will
      take place at 6 months. Study outcomes will be measured by a questionnaire at 7
      months. Phase 1 will allow us to estimate the prevalence of urinary, sexual,
      bowel and hormone-related problems in prostate cancer survivors and the level of
      unmet needs. 'Usual care' will also be documented. Phase 2 will provide
      information on recruitment and retention, acceptability of the
      intervention/outcome measures, effect sizes of the intervention and cost
      effectiveness data, which is required to inform development of a larger, phase 3
      randomised controlled trial. The main outcome of interest is change in prostate
      cancer-related quality of life. Methodological issues will also be addressed.
      ETHICS AND DISSEMINATION: Ethics approval has been gained (Oxford REC A
      12/SC/0500). Findings will be disseminated in peer-reviewed journals, at
      conferences, through user networks and relevant clinical groups. TRIAL
      REGISTRATION NUMBER: ISRCTN 97242511.

PMID- 24852303
TI  - Characterization of nineteen microsatellite markers and development of multiplex
      PCRs for the wedge clam Donax trunculus (Mollusca: Bivalvia).
AB  - The wedge clam Donax trunculus is an Atlantic-Mediterranean warm-temperate
      species found from Senegal to the northern coast of France, including the
      Mediterranean and Black Sea. It is commercially exploited in several European
      countries and constitutes an important fishing resource due to its high
      economical value. To contribute to its conservation and management, nineteen
      microsatellite markers were isolated from two enriched genomic libraries. These
      loci were characterized in 30 clams from a single population from northwest
      Spain. The number of alleles per locus ranged from 2 to 17 and observed and
      expected heterozygosity varied from zero to 0.714 and from 0.078 to 0.950,
      respectively. Linkage disequilibrium was not detected and nine loci were in
      agreement with Hardy-Weinberg equilibrium. Fifteen polymorphic markers were
      arranged into three multiplex PCR sets to reduce both time and cost of
      microsatellite genotyping. This is the first time that polymorphic microsatellite
      markers have been reported for D. trunculus. These new markers provide a valuable
      resource for future population genetics studies and management and culture of
      this species. 

PMID- 24852302
TI  - The role of team climate in improving the quality of chronic care delivery: a
      longitudinal study among professionals working with chronically ill adolescents
      in transitional care programmes.
AB  - OBJECTIVES: This study aimed to (1) evaluate the effectiveness of implementing
      transition programmes in improving the quality of chronic care delivery and (2)
      identify the predictive role of (changes in) team climate on the quality of
      chronic care delivery over time. SETTINGS: This longitudinal study was undertaken
      with professionals working in hospitals and rehabilitation units that
      participated in the transition programme 'On Your Own Feet Ahead!' in the
      Netherlands. PARTICIPANTSS: A total of 145/180 respondents (80.6%) filled in the
      questionnaire at the beginning of the programme (T1), and 101/173 respondents
      (58.4%) did so 1 year later at the end of the programme (T2). A total of 90 (52%)
      respondents filled in the questionnaire at both time points. Two-tailed, paired t
      tests were used to investigate improvements over time and multilevel analyses to
      investigate the predictive role of (changes in) team climate on the quality of
      chronic care delivery. INTERVENTIONS: Transition programme. PRIMARY OUTCOME
      MEASURES: Quality of chronic care delivery measured with the Assessment of
      Chronic Illness Care Short version (ACIC-S). RESULTS: The overall ACIC-S score at
      T1 was 5.90, indicating basic or intermediate support for chronic care delivery.
      The mean ACIC-S score at T2 significantly improved to 6.70, indicating advanced
      support for chronic care. After adjusting for the quality of chronic care
      delivery at T1 and significant respondents' characteristics, multilevel
      regression analyses showed that team climate at T1 (p<0.01) and changes in team
      climate (p<0.001) predicted the quality of chronic care delivery at T2.
      CONCLUSIONS: The implementation of transition programmes requires a supportive
      and stimulating team climate to enhance the quality of chronic care delivery to
      chronically ill adolescents.

PMID- 24852304
TI  - Polymorphism of killer cell immunoglobulin-like receptors (KIR) and their HLA
      ligands in Graves' disease.
AB  - Killer immunoglobulin-like receptors (KIR) play a pivotal role in commencement of
      both innate and adaptive immunity. Dysregulation of KIRs is associated with an
      increased risk of autoimmune disorders. This study was designed to assess whether
      polymorphisms in KIR gene family and their respective HLA class I ligands confer
      protection or susceptibly to Graves' disease (GD). Eighty patients with confirmed
      GD (cases) and 176 healthy unrelated subjects (controls) were recruited. Using a
      polymerase chain reaction sequence-specific primer directed method (PCR-SSP),
      presence or absence of KIR genes and their HLA ligands were determined. No
      significant differences were observed between case and control groups regarding
      individual KIR gene frequencies (p > 0.05 in all cases). The frequency of group A
      haplotype (the most common KIR haplotype, encompassing
      2DL1/2DL3/3DL1/2DS4/2DP1/3DP1/2DL4/3DL2/3DL3), was not different between
      individuals with and without GD. Moreover, among all other haplotypes (group Bx),
      no significant differences regarding distribution of centromeric and telomeric
      gene clusters were identifiable. Inhibitory/activatory gene contents were also
      comparable between the two groups. Four models of KIR-HLA interaction
      (inhibition, activation, unrestrained inhibition, and unrestrained activation)
      were constructed. No combination proved to confer susceptibility to, or offer
      protection against GD. It seems that the contribution of KIR gene polymorphism to
      natural killer cell dysfunction and other autoimmune abnormalities observed in GD
      is limited.

PMID- 24852305
TI  - Molecular studies of the structural ecology of natural occlusal caries.
AB  - Microbiological studies of occlusal dental biofilms have hitherto been hampered
      by inaccessibility to the sampling site and demolition of the original biofilm
      architecture. This study shows for the first time the spatial distribution of
      bacterial taxa in vivo at various stages of occlusal caries, applying a molecular
      methodology involving preparation of embedded hard dental tissue slices for
      fluorescence in situ hybridization (FISH) and confocal microscopy. Eleven freshly
      extracted teeth were classified according to their occlusal caries status. The
      teeth were fixed, embedded, sectioned and decalcified before FISH was performed
      using oligonucleotide probes for selected abundant species/genera associated with
      occlusal caries including Streptococcus, Actinomyces, Veillonella, Fusobacterium,
      Lactobacillus and Bifidobacterium. The sites showed distinct differences in the
      bacterial composition between different ecological niches in occlusal caries.
      Biofilm observed along the entrance of fissures showed an inner layer of
      microorganisms organized in palisades often identified as Actinomyces, covered by
      a more loosely structured bacterial layer consisting of diverse genera, similar
      to supragingival biofilm. Biofilm within the fissure proper seemed less
      metabolically active, as judged by low fluorescence signal intensity and presence
      of material of non-bacterial origin. Bacterial invasion (often Lactobacillus and
      Bifidobacterium spp.) into the dentinal tubules was seen only at advanced stages
      of caries with manifest cavity formation. It is concluded that the molecular
      methodology represents a valuable supplement to previous methods for the study of
      microbial ecology in caries by allowing analysis of the structural composition of
      the undisturbed biofilm in caries lesions in vivo.

PMID- 24852306
TI  - Effect of a rye dwarfing gene on plant height, heading stage, and Fusarium head
      blight in triticale (*Triticosecale Wittmack).
AB  - KEY MESSAGE: The rye-derived dwarfing gene Ddw1 on chromosome 5R acts in
      triticale in considerably reducing plant height, increasing FHB severity and
      delaying heading stage. Triticale, an amphiploid hybrid between durum wheat and
      rye, is an European cereal mainly grown in Germany, France, Poland, and Belarus
      for feeding purposes. Dwarfing genes might further improve the genetic potential
      of triticale concerning lodging resistance and yield. However, they might have
      pleiotropic effects on other, agronomically important traits including Fusarium
      head blight. Therefore, we analyzed a population of 199 doubled haploid (DH)
      lines of the cross HeTi117-06 * Pigmej for plant height, heading stage, and FHB
      severity across 2 locations and 2 years. The most prominent QTL was detected on
      chromosome 5R explaining 48, 77, and 71 % of genotypic variation for FHB
      severity, plant height, and heading stage, respectively. The frequency of
      recovery in cross validation was >=90 % for all three traits. Because the markers
      that detect dwarfing gene Ddw1 in rye are also in our population the most closely
      linked markers, we assume that this major QTL resembles Ddw1. For FHB severity
      two, for plant height three, and for heading stage five additional QTL were
      detected. Caused by the considerable genetic variation for heading stage and FHB
      severity within the progeny with the dwarfing allele, short-strawed, early
      heading and FHB-resistant lines can be developed when population size is large
      enough.

PMID- 24852308
TI  - Are advance directives associated with better hospice care?
AB  - OBJECTIVES: To describe individuals with advance directives at the time of
      hospice enrollment and to determine whether they have patterns of care and
      outcomes that are different from those of individuals without advance directives.
      DESIGN: Electronic health record-based retrospective cohort study with propensity
      score-adjusted analysis. SETTING: Three hospice programs in the United States.
      PARTICIPANTS: Individuals admitted to hospice between January 1, 2008, and May
      15, 2012 (N = 49,370). MEASUREMENTS: Timing of hospice enrollment before death,
      rates of voluntary withdrawal from hospice, and site of death. RESULTS: Most
      participants (35,968, 73%) had advance directives at the time of hospice
      enrollment. These participants were enrolled in hospice longer (median 29 vs 15
      days) and had longer survival times before death (adjusted hazard ratio = 0.62;
      95% confidence interval (CI) 0.58-0.66; P < .001). They were less likely to die
      within the first week after hospice enrollment (24.3% vs 33.2%; adjusted odds
      ratio (aOR) = 0.83, 95% CI = 0.78-0.88; P < .001). Participants with advance
      directives were less likely to leave hospice voluntarily (2.2% vs 3.4%; aOR =
      0.82, 95% CI = 0.74-0.90; P = .003) and more likely to die at home or in a
      nursing home than in an inpatient unit (15.3% vs 25.8%; aOR = 0.82, 95% CI = 0.77
      0.87; P < .001). CONCLUSION: Participants with advance directives were enrolled
      in hospice for a longer period of time before death than those without and were
      more likely to die in the setting of their choice.

PMID- 24852307
TI  - The interface between methyltransferase and polymerase of NS5 is essential for
      flavivirus replication.
AB  - The flavivirus NS5 harbors both a methyltransferase (MTase) and an RNA-dependent
      RNA polymerase (RdRP). Both enzyme activities of NS5 are critical for viral
      replication. Recently, the full-length NS5 crystal structure of Japanese
      encephalitis virus reveals a conserved MTase-RdRP interface that features two
      conserved components: a six-residue hydrophobic network and a GTR sequence. Here
      we showed for the first time that these key interface components are essential
      for flavivirus replication by various reverse genetics approaches. Interestingly,
      some replication-impaired variants generated a common compensatory NS5 mutation
      outside the interface (L322F), providing novel routes to further explore the
      crosstalk between MTase and RdRP. 

PMID- 24852309
TI  - Measurement of serum TNF alpha as a sensitive and specific marker in diagnosing
      extrahepatic biliary atresia.

PMID- 24852310
TI  - Retrospective analysis of operated cases of post appendectomy small bowel
      obstruction in a tertiary care centre.

PMID- 24852311
TI  - Theoretical study of the oxidation mechanisms of naphthalene initiated by
      hydroxyl radicals: the OH-addition pathway.
AB  - The oxidation mechanisms of naphthalene by OH radicals under inert (He)
      conditions have been studied using density functional theory along with various
      exchange-correlation functionals. Comparison has been made with benchmark CBS-QB3
      theoretical results. Kinetic rate constants were correspondingly estimated by
      means of transition state theory and statistical Rice-Ramsperger-Kassel-Marcus
      (RRKM) theory. Comparison with experiment confirms that, on the OH-addition
      reaction pathway leading to 1-naphthol, the first bimolecular reaction step has
      an effective negative activation energy around -1.5 kcal mol(-1), whereas this
      step is characterized by an activation energy around 1 kcal mol(-1) on the OH
      addition reaction pathway leading to 2-naphthol. Effective rate constants have
      been calculated according to a steady state analysis upon a two-step model
      reaction mechanism. In line with experiment, the correspondingly obtained
      branching ratios indicate that, at temperatures lower than 410 K, the most
      abundant product resulting from the oxidation of naphthalene by OH radicals must
      be 1-naphthol. The regioselectivity of the OH(*)-addition onto naphthalene
      decreases with increasing temperatures and decreasing pressures. Because of
      slightly positive or even negative activation energies, the RRKM calculations
      demonstrate that the transition state approximation breaks down at ambient
      pressure (1 bar) for the first bimolecular reaction steps. Overwhelmingly high
      pressures, larger than 10(5) bar, would be required for restoring to some extent
      (within ~5% accuracy) the validity of this approximation for all the reaction
      channels that are involved in the OH-addition pathway. Analysis of the computed
      structures, bond orders, and free energy profiles demonstrate that all reaction
      steps involved in the oxidation of naphthalene by OH radicals satisfy Leffler
      Hammond's principle. Nucleus independent chemical shift indices and natural bond
      orbital analysis also show that the computed activation and reaction energies are
      largely dictated by alterations of aromaticity, and, to a lesser extent, by
      anomeric and hyperconjugative effects. 

PMID- 24852312
TI  - Algorithmic approach to solid adnexal masses and their mimics: utilization of
      anatomic relationships and imaging features to facilitate diagnosis.
AB  - Solid adnexal masses, while less common than their cystic counterparts, may
      present a challenge for radiologists given the wide range of histologic entities
      that occur in this region. Pelvic masses, especially when large, can seem
      overwhelming at first but application of an algorithmic approach allows for more
      confident assessment. This approach focuses first on the use of anatomic
      relationships and interactions of various pelvic structures to localize the mass'
      origin. For instance, the directionality of ureteral displacement can suggest if
      a mass is intra or extraperitoneal. Then, key discriminating imaging features,
      such as the presence of fat, hypervascularity, or low T2 signal on magnetic
      resonance imaging (MRI) can be applied to further narrow the list of diagnostic
      possibilities. Entities such as leiomyomas, nerve sheath tumors, congenital
      uterine anomalies, and vascular abnormalities (ovarian torsion or iliac vessel
      aneurysm) in particular are often accurately characterized with sonography and/or
      MRI. For solid adnexal masses in which a definitive diagnosis by imaging is not
      reached, information germane to clinicians regarding further management can still
      be provided, principally with regard to surgical vs. nonsurgical treatment. 

PMID- 24852313
TI  - Multi detector computed tomography (MDCT) for the diagnosis of early
      complications after pancreas transplantation.
AB  - PURPOSE: Solitary Pancreas (SPT) and simultaneous kidney-pancreas (SPKT)
      transplants carry a high risk of surgical complications that may lead to the loss
      of the pancreas graft and impact later kidney function. The purpose of this study
      was to investigate the role of MDCT in the diagnosis of early complications and
      its impact on kidney function. METHODS: All patients receiving SPT or SPKT over 5
      years were retrospectively included. Complications that occurred within the first
      15 days were registered and MDCT data analyzed. Data regarding donor, transplant,
      and recipient characteristics as well as transplantation procedures were analyzed
      according to the occurrence of early complications. Kidney function at day 3
      following MDCT was evaluated. RESULTS: One hundred and forty-one patients were
      included (85 men, 56 women; mean age 40.1 years, SD 7.7) with 119 SPKT and 22
      SPT. Sixty-four complications were registered in 50 patients. Partial (P-) or
      complete venous thrombosis (C-VT) occurred in 12.1 % (n = 17), arterial
      thrombosis (AT) in 1.4 % (n = 2), and hemorrhage in 8.5 % (n = 12) of all
      patients. For venous thrombosis, the predominant risk factor was body mass index
      (BMI) for either recipients (P < 0.05) or donors (P < 0.01). Median time for
      venous thrombosis diagnosis with MDCT was 4 days. Kidney function was not altered
      following MDCT. Fourteen pancreatectomies were necessary. All patients with C-VT
      and AT had to undergo graftectomy. CONCLUSION: Vascular complications occurred
      early following grafting. Systematic early-enhanced MDCT at day 2-3 should be
      adequate to detect early thrombosis, especially if risk factors have been
      identified, without induced kidney function alteration.

PMID- 24852314
TI  - A fullerene-carbene adduct as a crystalline molecular rotor: remarkable behavior
      of a spherically-shaped rotator.
AB  - A new fullerene structure was recently obtained from the reaction of a Lewis
      basic N-heterocyclic carbene (NHC) and the Lewis acidic C60. The molecular
      features of the zwitterionic adduct can be described as a molecular rotor with
      the fullerene cage acting as the rotator that spins about one distinct axis given
      by its C-C single bond linkage with the imidazolium heterocycle stator. A
      detailed structural analysis of the compound by means of single-crystal X-ray
      diffraction (XRD) revealed significant differences in the packing motifs of
      solvent-free and solvent-containing crystals. Variable temperature single-crystal
      XRD experiments (80 K <= T <= 480 K) carried out to investigate the rotational
      dynamics of the fullerene group in the higher quality solvent-free structure
      revealed atomic displacement parameters consistent with fast rotation of the
      highly symmetric fullerene in the solid state, whereas the imidazolium unit
      remains in a fixed position and therefore represents the stator. DFT and
      semiempirical calculations were applied to get insight into the profile of the
      rotational potential of the fullerene unit, particularly considering interactions
      with the neighboring molecules in the crystal lattice. The results indicate that
      the crystal environment leads to the presence of one lowest energy minimum that
      is connected to seven others that are slightly higher in energy through
      rotational barriers of approximately 1.5-2.5 kcal mol(-1). 

PMID- 24852315
TI  - Neoadjuvant, anthracycline-free chemotherapy with carboplatin and docetaxel in
      triple-negative, early-stage breast cancer: a multicentric analysis of
      feasibility and rates of pathologic complete response.
AB  - BACKGROUND: Triple-negative breast cancer (TNBC) attracts a disproportionate
      share of intensive research because of its poor prognosis. Standard anthracycline
      and taxane-based regimens still yield an unsatisfactorily low rate of pathologic
      complete response (pCR). The pCR rate is a recognized surrogate marker for good
      long-term survival. METHODS: A multicentric, retrospective study was conducted
      including all patients not willing to undergo or not suitable for an
      anthracycline-based regimen. Six cycles of docetaxel 75 mg/m(2) and carboplatin
      AUC 6 q3w were administered. The primary endpoint was pCR (ypT0/ypTis + ypN0) and
      near-pCR (<=5 mm residual disease). The secondary endpoint was feasibility (CTCAE
      version 4.03 criteria) and adherence to treatment. RESULTS: Six cycles of
      carboplatin AUC 6 and docetaxel 75 mg/m(2) resulted in a high pCR rate of 50% and
      a combined pCR/near-pCR rate of 70%. Grade 3 and 4 toxicities were rare events
      and 28 of 30 (93%) patients completed all 6 cycles. No toxicity-related treatment
      discontinuation and no febrile neutropenia were registered. CONCLUSION: This
      chemotherapy regimen provides a highly effective and feasible strategy for
      patients not willing to receive or not suitable for an anthracycline-based
      treatment (cardiac ejection fraction <65% or age >65 years). Combinations of
      platinum compounds with taxanes and anthracyclines may be also desirable in TNBC.

PMID- 24852316
TI  - The neural basis of self-face recognition after self-concept threat and
      comparison with important others.
AB  - The implicit positive association (IPA) theory attributed self-face advantage to
      the IPA with self-concept. Previous behavioral study has found that self-concept
      threat (SCT) could eliminate the self-advantage in face recognition over familiar
      face, without taking levels of facial familiarity into account. The current event
      related potential study aimed to investigate whether SCT could eliminate the self
      face advantage over stranger-face. Fifteen participants completed a "self-friend"
      comparison task in which participants identified the face orientation of self
      face and friend-face after SCT and non-self-concept threat (NSCT) priming, and a
      "self-stranger" comparison task was also completed in which participants
      identified the face orientation of self-face and stranger-face after SCT and NSCT
      priming. The results showed that the N2 amplitudes were more negative for
      processing friend-face than self-face after NSCT priming, but there was no
      significant difference between them after SCT priming. Moreover, the N2
      amplitudes were more negative for processing stranger-face than self-face both
      after SCT priming and after NSCT priming. Furthermore, SCT manipulated the N2
      amplitudes of friend-face rather than self-face. Overall, the present study made
      a supplementary to the current IPA theory and further indicated that SCT would
      only eliminate this self-face recognition advantage when comparing with important
      others.

PMID- 24852317
TI  - Spironolactone inhibits production of proinflammatory mediators in response to
      lipopolysaccharide via inactivation of nuclear factor-kappaB.
AB  - The effect of spironolactone (SPIR) on lipopolysaccharide (LPS)-induced
      production of proinflammatory mediators was examined using RAW 264.7 macrophage
      like cells and mouse peritoneal macrophages. SPIR significantly inhibited LPS
      induced production of nitric oxide (NO), tumor necrosis factor-alpha and
      prostaglandin E2. The inhibition was not mediated by cell death. SPIR reduced the
      expression of an inducible NO synthase mRNA in response to LPS. SPIR
      significantly inhibited phosphorylation of p65 nuclear factor (NF)-kappaB in
      response to LPS. Furthermore, SPIR inhibited phosphorylation of IkappaB kinase
      (IKK) as an upstream molecule of NF-kappaB in response to LPS. LPS did not induce
      the production of aldosterone in RAW 264.7 cells. Taken together, SPIR is
      suggested to inhibit LPS-induced proinflammatory mediators via inactivation of
      IKK/NF-kappaB in LPS signaling.

PMID- 24852318
TI  - Class A dioscorins of various yam species suppress ovalbumin-induced allergic
      reactions.
AB  - CONTEXT: Dioscorins, the primary storage proteins in yam tubers, of different
      species exhibited varying immunomodulatory activities in mice. We inferred that
      this might be attributed to the various isoforms in the yam tubers. OBJECTIVE: We
      aimed to investigate the antiallergic potential of the Class A dioscorins of
      various yam species using the ovalbumin (OVA)-induced murine allergy model.
      MATERIALS AND METHODS: We purified the recombinant Class A dioscorins
      (rDioscorins) of various yam species from Escherichia coli and evaluated their
      antiallergic potential by enzyme-linked immunosorbent assay. RESULTS: The Class A
      rDioscorins of various yam species suppressed allergic reactions by significantly
      decreasing the serum IgE and histamine levels. The serum IFN-gamma and IgG2a
      levels significantly increased in all rDioscorin-treated mice. The splenocytes of
      the rDioscorin-treated mice also exhibited upregulated IFN-gamma secretion in
      response to ConA stimulation. By contrast, the serum IL-5 levels decreased to
      basal levels in mice treated with Class A rDioscorins and the amount of IL-5
      produced by splenocytes decreased in response to ConA stimulation. DISCUSSION:
      The Class A rDioscorins suppress allergic reactions, possibly through modulating
      an imbalanced Th1/Th2 immune response to OVA by promoting Th1 cell responses.
      Furthermore, the Class A rDioscorins of various yam species exhibited similar
      immunomodulatory activities in OVA-sensitized mice, which were different from the
      activities demonstrated by native dioscorins, suggesting that distinct
      immunomodulatory effects of native dioscorins on mice were attributed to the
      various isoforms in the yam tubers. CONCLUSION: The Class A dioscorins of various
      yam species exhibit antiallergic activity and are potential immunotherapeutic
      agents for treating IgE-mediated hypersensitivity.

PMID- 24852319
TI  - Imaging diagnosis--computed tomographic, surgical, and histopathologic
      characteristics of an infiltrative angiolipoma in a dog.
AB  - A 6-year-old female spayed Shetland Sheepdog presented for evaluation of a
      subcutaneous mass over the right prescapular region. The mass had been
      cytologically diagnosed as a lipoma by the referring veterinarian 20 months
      prior, but had grown significantly and was very firm. CT scan of the mass was
      suggestive of neoplasia; however, the tissue of origin could not be determined.
      Histopathologic evaluation diagnosed infiltrative angiolipoma, and marginal
      resection of the tumor was performed. Infiltrative angiolipomas are benign but
      locally aggressive neoplasms uncommonly reported in veterinary medicine. This
      report correlates the clinical, CT, and histopathologic characteristics of an
      infiltrative angiolipoma. 

PMID- 24852320
TI  - Acetate treatment increases fatty acid content in LPS-stimulated BV2 microglia.
AB  - Acetate supplementation increases plasma acetate, brain acetyl-CoA, histone
      acetylation, phosphocreatine levels, and is anti-inflammatory in models of
      neuroinflammation and neuroborreliosis. Although radiolabeled acetate is
      incorporated into the cellular lipid pools, the effect that acetate
      supplementation has on lipid deposition has not been quantified. To determine the
      impact acetate-treatment has on cellular lipid content, we investigated the
      effect of acetate in the presence of bacterial lipopolysaccharide (LPS) on fatty
      acid, phospholipid, and cholesterol content in BV2 microglia. We found that 1, 5,
      and 10 mM of acetate in the presence of LPS increased the total fatty acid
      content in BV2 cells by 23, 34, and 14 % at 2 h, respectively. Significant
      increases in individual fatty acids were also observed with all acetate
      concentrations tested with the greatest increases occurring with 5 mM acetate in
      the presence of LPS. Treatment with 5 mM acetate in the absence of LPS increased
      total cholesterol levels by 11 %. However, neither treatment in the absence of
      LPS significantly altered the content of individual phospholipids or total
      phospholipid content. To determine the minimum effective concentration of acetate
      we measured the time- and concentration-dependent changes in histone acetylation
      using western blot analysis. These studies showed that 5 mM acetate was necessary
      to induce histone acetylation and at 10 mM acetate, the histone acetylation-state
      increased as early as 0.5 h following the start of treatment. These data suggest
      that acetate increases fatty acid content in LPS-stimulated BV2 microglia that is
      reflected by an increase in fatty acids esterified into membrane phospholipids.

PMID- 24852321
TI  - Regulation of diacylglycerol kinase delta2 expression in C2C12 skeletal muscle
      cells by free fatty acids.
AB  - Decreased expression of diacylglycerol kinase (DGK) delta in skeletal muscles is
      closely related to the pathogenesis of type 2 diabetes. However, the regulation
      of DGKdelta expression is not well understood. In this study, we found that
      myristic acid (14:0) significantly increased DGKdelta2 protein expression in a
      dose-dependent manner (EC(50) = 0.16 mM) in mouse C2C12 myotubes. In contrast,
      oleic [18:1(n-9)], eicosenoic [20:1(n-9)] and erucic [22:1(n-9)] acids markedly
      decreased DGKdelta2 expression. Myristic acid slowly enhanced DGKdelta2
      expression at the transcription level. Therefore, DGKdelta2 expression is
      positively regulated by the relatively short-chain saturated fatty acid myristic
      acid but attenuated by n-9 monounsaturated fatty acids.

PMID- 24852322
TI  - Progression from mild cognitive impairment to dementia: a 3-year longitudinal
      study.
AB  - OBJECTIVE: To examine characteristics that predict the progression from mild
      cognitive impairment to dementia. METHODS: Of 970 patients recruited from nine
      memory clinics around Australia, 185 had mild cognitive impairment diagnosed.
      Measures of cognitive ability, functional ability, and neuropsychiatric symptoms
      were completed at baseline and over 3 years of follow up. RESULTS: Over 3 years,
      52 (28%) patients with mild cognitive impairment developed dementia. Older age,
      lower cognitive ability at baseline, and faster decline in cognitive ability over
      the first 6 months of follow up, but not depression, predicted progression to
      dementia. CONCLUSIONS: The findings confirm that simple clinical data such as
      age, cognitive ability at baseline, and rate of cognitive decline are important
      predictors of progression from mild cognitive impairment to dementia over 3
      years.

PMID- 24852323
TI  - Psychological outcomes following the Victorian Black Saturday bushfires.
AB  - OBJECTIVE: We aimed to map the prevalence and predictors of psychological
      outcomes in affected communities 3-4 years after the Black Saturday bushfires in
      the state of Victoria, Australia. METHODS: Baseline assessment of a longitudinal
      cohort study in high-, medium-, and low-affected communities in Victoria.
      Participants included 1017 residents of high-, medium-, and low-affected fire
      communities. Participants were surveyed by means of a telephone and web-based
      interview between December 2011 and January 2013. The survey included measures of
      fire-related post-traumatic stress disorder (PTSD) and general PTSD from other
      traumatic events, major depressive episode, alcohol use, and general
      psychological distress. RESULTS: The majority of respondents in the high-
      (77.3%), medium- (81.3%), and low-affected (84.9%) communities reported no
      psychological distress on the K6 screening scale. More participants in the high
      affected communities (15.6%) reported probable PTSD linked to the bushfires than
      medium- (7.2%) and low-affected (1.0%) communities (odds ratio (OR): 4.57, 95%
      confidence interval (CI): 2.61-8.00, p = 0.000). Similar patterns were observed
      for depression (12.9%, 8.8%, 6.3%, respectively) (OR: 1.83, 95% CI: 1.17-2.85, p
      = 0.008) and severe psychological distress (9.8%, 5.0%, 4.9%, respectively) (OR:
      2.08, 95% CI: 1.23-3.55, p = 0.007). All communities reported elevated rates of
      heavy drinking (24.7%, 18.7%, 19.6%, respectively); however, these were higher in
      the high-affected communities (OR: 1.39, 95% CI: 1.01-1.89, p = 0.04). Severe
      psychological distress was predicted by fear for one's life in the bushfires,
      death of someone close to them in the bushfires, and subsequent stressors. One
      third of those with severe psychological distress did not receive mental health
      assistance in the previous month. CONCLUSIONS: Several years following the Black
      Saturday bushfires the majority of affected people demonstrated resilience
      without indications of psychological distress. A significant minority of people
      in the high-affected communities reported persistent PTSD, depression, and
      psychological distress, indicating the need for promotion of the use of health
      and complementary services, community-based initiatives, and family and other
      informal supports, to target these persistent problems.

PMID- 24852324
TI  - Tying up loose ends: a method for constructing and evaluating decision aids that
      meet blunt and sharp-end goals.
AB  - We present a methodological framework for constructing and evaluating decision
      aids--fast and frugal trees (FFTs)--ideally suited to the front line of an
      organisation. Their performance can be analysed in signal detection theory,
      allowing for transparent selection of FFTs given managerial-level trade-offs
      among type I and II errors. We extend FFTs from binary classification to
      selection from multiple actions (FFT multiple) as well as performance analysis to
      organisational goal states beyond type I and II error reduction. Concepts and
      framework are introduced and a tutorial-style example application (threat
      assessment at military checkpoints) is provided. Throughout, we discuss ways to
      deal with missing or incomplete data and show that the performance of decision
      aids may be overestimated if the effectiveness of actions is not heeded. The
      methodology can be used to construct and evaluate decision aids in any area
      characterised by dichotomised cues and a one-to-many mapping between
      categorisation outcomes and actions.

PMID- 24852325
TI  - Monocytes and CD4+ T cells contribution to the under-expression of NR4A2 and
      TNFAIP3 genes in patients with multiple sclerosis.
AB  - We recently found a gene signature for multiple sclerosis (MS) that reverted to
      normal during pregnancy in MS patients and included NR4A2 and TNFAIP3, key
      molecules in anti-inflammatory processes. Here we focus on the expression levels
      of these two genes in monocytes and CD4+ T cells from healthy controls and
      treatment-naive RRMS patients. Our findings show that monocytes play a key role
      in the dysregulated anti-inflammatory response, being the expression of both
      genes down-regulated in these cells in RRMS patients with respect to healthy
      individuals. CD4+ T cells seem to have only a marginal part, because we can
      observe only a slight down-regulation in NR4A2. 

PMID- 24852326
TI  - Amino acids as co-amorphous excipients for simvastatin and glibenclamide:
      physical properties and stability.
AB  - Co-amorphous drug mixtures with low-molecular-weight excipients have recently
      been shown to be a promising approach for stabilization of amorphous drugs and
      thus to be an alternative to the traditional amorphous solid dispersion approach
      using polymers. However, the previous studies are limited to a few drugs and
      amino acids. To facilitate the rational selection of amino acids, the practical
      importance of the amino acid coming from the biological target site of the drug
      (and associated intermolecular interactions) needs to be established. In the
      present study, the formation of co-amorphous systems using cryomilling and
      combinations of two poorly water-soluble drugs (simvastatin and glibenclamide)
      with the amino acids aspartic acid, lysine, serine, and threonine was
      investigated. Solid-state characterization with X-ray powder diffraction,
      differential scanning calorimetry, and Fourier-transform infrared spectroscopy
      revealed that the 1:1 molar combinations simvastatin-lysine, glibenclamide
      serine, and glibenclamide-threonine and the 1:1:1 molar combination glibenclamide
      serine-threonine formed co-amorphous mixtures. These were homogeneous single
      phase blends with weak intermolecular interactions in the mixtures.
      Interestingly, a favorable effect by the excipients on the tautomerism of
      amorphous glibenclamide in the co-amorphous blends was seen, as the formation of
      the thermodynamically less stable imidic acid tautomer of glibenclamide was
      suppressed compared to that of the pure amorphous drug. Furthermore, the co
      amorphous mixtures provided a physical stability advantage over the amorphous
      drugs alone. 

PMID- 24852327
TI  - Intrapleural minocycline pleurodesis for the treatment of primary spontaneous
      pneumothorax.
AB  - PURPOSE OF REVIEW: The role of chemical pleurodesis in the treatment of primary
      spontaneous pneumothorax remains unclear. According to current practice
      guidelines, chemical pleurodesis is reserved for patients who are unable or
      unwilling to have surgery. Some recent studies showed that intrapleural
      minocycline pleurodesis could decrease the rate of pneumothorax recurrence, when
      used either as the initial treatment for simple pneumothorax after successful
      aspiration and drainage or as an adjuvant treatment for complicated or recurrent
      pneumothorax following thoracoscopic surgery. The purpose of this review is to
      discuss the current available evidence on intrapleural minocycline pleurodesis
      for the treatment of primary spontaneous pneumothorax. RECENT FINDINGS: In a
      recently published prospective, randomized controlled trial, additional
      minocycline pleurodesis following simple aspiration and drainage was a well
      tolerated and more effective initial treatment for a first episode of primary
      spontaneous pneumothorax than simple aspiration and drainage alone. Other
      prospective, randomized controlled trials showed that additional minocycline
      pleurodesis after thoracoscopic treatment was a well tolerated and convenient
      procedure which can reduce the rate of ipsilateral recurrence of primary
      spontaneous pneumothorax. SUMMARY: Intrapleural minocycline pleurodesis can be
      considered an adjunct to standard treatment of primary spontaneous pneumothorax,
      after either simple aspiration and drainage or after thoracoscopic surgery.

PMID- 24852328
TI  - Thoracentesis and the risks for bleeding: a new era.
AB  - PURPOSE OF REVIEW: Thoracentesis is a commonly performed procedure throughout the
      world. Convention dictates that patients should have laboratory values such as
      international normalized ratio (INR) and platelets corrected or medications that
      affect bleeding withheld prior to performing this procedure. By transfusing blood
      products or withholding medications, patients are exposed to risks that are
      different than but equally if not more significant than the risk of hemothorax
      from thoracentesis. This review highlights recent studies that suggest the
      parameters of performing thoracentesis should be less stringent than
      traditionally thought. RECENT FINDINGS: Although the safety of thoracentesis has
      improved with the use of ultrasound and other advancements, the number of
      patients on new medications that exert an influence on bleeding and those who
      have physiologic coagulation abnormalities continues to grow. Despite a 1991
      study demonstrating the safety of thoracentesis in patients with an abnormal INR
      or low platelet count, transfusion of blood products to normalize laboratory
      values is commonplace. A number of studies within the past year address the
      safety of thoracentesis amidst INR and platelet abnormalities and in patients
      taking antiplatelet or other medications that affect a patient's bleeding
      potential. SUMMARY: Although large randomized studies do not exist, recent
      literature suggests that it is time to reevaluate the need to correct INR and
      platelet counts or to transfuse blood products or withhold medications prior to
      thoracentesis in patients felt to have a risk of possible bleeding.

PMID- 24852329
TI  - High-grade lung adenocarcinomas with micropapillary and/or solid patterns: a
      review.
AB  - PURPOSE OF REVIEW: The purpose of review is to discuss the most recent research
      findings on lung adenocarcinomas with solid and micropapillary patterns. RECENT
      FINDINGS: Multiple recent studies have confirmed that both patterns are
      associated with adverse clinicopathologic features such as lymphovascular and
      pleural invasion, as well as lymph node metastasis, and consequently with poor
      disease-free survival, overall survival, or both. Radiologic characteristics such
      as high F-fluorodeoxyglucose (FDG) uptake, a solid nodule, and size >=2 cm have
      been found to be useful to detect solid and micropapillary patterns. A seminal
      study has shown that the presence of a micropapillary component (>=5%) is a risk
      factor for early locoregional recurrence in patients undergoing limited resection
      for small (<2 cm) adenocarcinomas, but not for patients undergoing lobectomy.
      Several studies have demonstrated that micropapillary-predominant tumors are
      associated with EGFR mutations, whereas solid-predominant tumors are negatively
      associated with mutations of this gene and positively associated with KRAS
      mutations, indicative of the lack of response to EGFR tyrosine kinase inhibitors.
      The possible role of molecular events such as loss of BRG1/BRM and activation of
      c-Met has been identified in solid pattern and micropapillary pattern,
      respectively. SUMMARY: Micropapillary and solid patterns are markers for early
      recurrence and poor survival in lung adenocarcinomas. In order to overcome the
      unfavorable outcomes, the preoperative detection of these patterns, development
      of targeted therapy for KRAS mutants, and discovery of biomarkers that play a
      significant role in development or progression or both of these patterns are
      warranted to help in treating lung adenocarcinoma patients with micropapillary or
      solid patterns or both effectively.

PMID- 24852330
TI  - Vincristine and irinotecan in children with relapsed hepatoblastoma: a single
      institution experience.
AB  - PURPOSE: This study was to determine the efficacy of vincristine and irinotecan
      in children with relapsed hepatoblastoma (HB). METHODS: A total of 10 patients
      with relapsed HB were enrolled. Three patients were excluded. Patients received
      irinotecan 50 mg/m(2)/day, day 1-5 and vincristine 1.5 mg/m(2)/day, day 1,
      repeated every 3 weeks. The maximum cycles were eight. Reevaluation of tumor was
      performed every two cycles. The primary outcome was the rate of complete
      resection. Secondary outcomes were event-free survival (EFS) and overall survival
      (OS). RESULTS: Of the seven patients assessable for response, one patient with
      normal AFP level showed a progressive disease and withdrew. He finally died 6
      months later. Four had PR, all of them underwent a second surgery and achieved
      complete resection. Two patients had SD, one patient relapsed 6 months after
      orthotopic liver transplantation and died, the other one undergoing surgery had
      micro margin positive, he relapsed again but alive. The rate of complete
      resection was 71.4% (including orthotopic liver transplantation). The 2-year EFS
      and OS for the whole group were 57.1% (95% CI, 12.7% to 34.2%) and 71.4% (95% CI,
      16.39% to 37.4%), respectively. CONCLUSIONS: The combination of irinotecan and
      vincristine has a significant antitumor activity and acceptable toxicity in
      children with relapsed HB.

PMID- 24852331
TI  - Crystal-momentum dispersion of ultrafast spin change in fcc Co.
AB  - Nearly twenty years ago, Beaurepaire and coworkers showed that when an ultrafast
      laser impinges on a ferromagnet, its spin moment undergoes a dramatic change, but
      how it works remains a mystery. While the current experiment is still unable to
      resolve the minute details of the spin change, crystal momentum-resolved
      techniques have long been used to analyze the charge dynamics in superconductors
      and strongly correlated materials. Here we extend it to probe spin moment change
      in the entire three-dimensional Brillouin zone for fcc Co. Our results indeed
      show a strong spin activity along the Delta line, supporting a prior experimental
      finding. The spin active pockets coalesce into a series of spin surfaces that
      follow the Fermi surfaces. We predict two largest spin change pockets which have
      been elusive to experiments: one pocket is slightly below the Delta line and the
      other is along the Lambda line and close to the L point. Our theory presents an
      opportunity for the time-, spin- and momentum-resolve photoemission technique. 

PMID- 24852333
TI  - Relation of gelsolin amyloidosis and periodontal health.
AB  - OBJECTIVE: Hereditary gelsolin amyloidosis (AGel amyloidosis) is a rare,
      dominantly inherited systemic disease with worldwide distribution, caused by a
      gelsolin gene mutation. We studied the periodontal conditions and microbiological
      plaque composition of AGel amyloidosis patients. MATERIAL AND METHODS: A
      voluntary study group of 36 AGel amyloidosis patients (mean age 61) filled in a
      questionnaire. A thorough periodontal examination included periodontal pocket
      depth and attachment level measurements, registrations of visible plaque,
      bleeding on probing and panoramic radiographs. The presence of oral Candida was
      studied by fungal culture method. Bacterial samples from deepened pockets (>=4
      mm) were analyzed with checkerboard DNA-DNA hybridization method. RESULTS: VPI
      (15.3 %) and BOP (11.2 %) of the patients were modest reflecting relatively
      adequate oral self-care. Still 89 % of the patients had at least one PPD of >=4
      mm; 78.5 % of the PPDs >=6 mm were found in molars. Patients had lost one third
      of the molars due to periodontitis and/or tooth decay. Half of the patients (53
      %) were Candida carriers. Bacterial analysis of subgingival plaque samples
      revealed bacterial species common to chronic periodontitis. CONCLUSION: AGel
      amyloidosis may increase the risk for periodontitis even when the oral self-care
      is adequate. Molar teeth appear to be mostly affected, leading to tooth loss.
      CLINICAL RELEVANCE: AGel amyloidosis as a systemic disease is related with a vast
      variety of symptoms with variable severity. Even though a causal relationship of
      the systemic disease and periodontitis has not yet been proven, increased risk
      for periodontal problems should be considered when examining AGel amyloidosis
      patients.

PMID- 24852332
TI  - Prenatal diagnosis of a placental infarction hematoma associated with fetal
      growth restriction, preeclampsia and fetal death: clinicopathological
      correlation.
AB  - The lesion termed 'placental infarction hematoma' is associated with fetal death
      and adverse perinatal outcome. Such a lesion has been associated with a high risk
      of fetal death and abruption placentae. The fetal and placental hemodynamic
      changes associated with placental infarction hematoma have not been reported.
      This paper describes a case of early and severe growth restriction with
      preeclampsia, and progressive deterioration of the fetal and placental Doppler
      parameters in the presence of a placental infarction hematoma.

PMID- 24852334
TI  - Surface scratch assessment of titanium implant abutments and cementum following
      instrumentation with metal curettes.
AB  - OBJECTIVES: This study was conducted to compare the surface scratch resistance of
      titanium implant abutments and cementum to evaluate the impact of scaling with
      metal curettes on both surfaces. MATERIALS AND METHODS: A standard in vitro force
      of 14 N was used to assess the scratch width and depth created by curettes on
      extracted human tooth roots and titanium implant abutments. Scratch width and
      depth were analysed using a stereomicroscope and non-contact surface
      profilometry. RESULTS: The mean force applied during test scaling procedures by
      experienced volunteer operators was 14 N. Mechanical scaling using this force in
      vitro of cementum produced a mean scratch width of 59.4 +/- 1.9 MUm, N = 20, and
      scratch depth of 0.86 +/- 0.03 MUm, N = 20, compared to the titanium abutments'
      mean scratch width of 30.8 +/- 1.9 MUm, N = 6, and scratch depth of 0.34 +/- 0.02
      MUm, N = 6. These differences were statistically significant (P < 0.05).
      CONCLUSIONS: Although there a number of factors in the clinical situation which
      are not easily reproducible in vitro, this proof-of-principle in vitro study is
      the first to confirm quantitatively that titanium abutments had a significantly
      greater scratch resistance than cementum when metal curettes were used on these
      surfaces. This information should be considered, especially if there is a
      preferred choice of metal instruments for effective dental prophylactic
      procedures for the maintenance of titanium dental implants. CLINICAL RELEVANCE:
      Clinical dogma suggests that titanium implant abutment surfaces should not be
      instrumented with metal instruments due to scratching of the surface. However,
      since cementum is softer than titanium, the logic of this tenet seems flawed.
      This study demonstrated for the first time that titanium abutments undergo less
      scratch damage during scaling with metal curettes than does cementum. Metal
      curettes may be used on titanium abutments with as much confidence as for root
      planing on natural teeth.

PMID- 24852335
TI  - Prevalence and management of chronic kidney disease in primary care patients in
      the UK.
AB  - BACKGROUND: This study aimed to estimate the prevalence of chronic kidney disease
      (CKD) in the UK in 2010 and to assess prevalence, comorbidities and comedications
      associated with the disease over time, following inclusion of CKD in the Quality
      and Outcomes Framework (QOF). METHODS: This was a retrospective, longitudinal
      study assessing individuals with prevalent or incident CKD (identified using
      estimated glomerular filtration rate readings and/or Read codes) in the General
      Practice Research Database (GPRD) in 2010. Individuals were assessed at two time
      points: in 2010 and at the date of their first classification of CKD in the GPRD.
      RESULTS: The prevalence of stage 3-5 CKD in 2010 was 5.9%. In patients with stage
      3-5 CKD at first classification, their disease remained stable, progressed or
      improved by 2010 in approximately 50%, 10-15% and 25-30% of patients,
      respectively. Diagnoses of cardiovascular-related comorbidities (hypertension,
      hypercholesterolaemia, diabetes and cardiovascular disease), and treatment with
      antihypertensives and lipid-modifying therapy (LMT), increased with worsening
      disease severity. When patients were stratified by diagnosis date, the proportion
      of patients with stage 3-5 CKD and cardiovascular-related comorbidities decreased
      with time, and the relative use of LMT and antihypertensives among patients with
      hypercholesterolaemia and hypertension increased with time. CONCLUSIONS: Chronic
      kidney disease is generally stable or progressive, although more patients improve
      disease stage than previously assumed. Data suggest that the introduction of CKD
      into the QOF has increased awareness of CKD among physicians in the UK, allowing
      for earlier intervention and better control of CKD progression.

PMID- 24852336
TI  - Cardiac 99mTc sestamibi SPECT and 18F FDG PET as viability markers in Takotsubo
      cardiomyopathy.
AB  - In patients with heart failure (HF) due to coronary disease, a combined
      evaluation of perfusion and glucose metabolism by cardiac single photon emission
      computed tomography (SPECT)/positron emission tomography (PET) can be used to
      distinguish viable from non-viable myocardium, and current guidelines recommend
      cardiac SPECT and fluorodeoxyglucose (FDG) PET for viability assessment.
      Takotsubo cardiomyopathy (TTC) is a disease characterized by acute but reversible
      HF leaving no scarring. To explore how robust the semi-quantitative viability
      criteria used in cardiac SPECT and FDG PET stands their ground in a population
      with TTC. From 1 September 2009 to 1 October 2012, 24 patients suspected of TTC
      were enrolled in a multimodality cardiac imaging research project.
      Echocardiography, (99m)Tc SPECT, and (18)F FDG PET were performed during the
      acute admission and at follow-up 4 months later. Nineteen patients had a final
      diagnosis of TTC consistent with Mayo Clinic Diagnostic Criteria. Three of these
      patients were excluded from further analysis, since wall motion abnormalities
      were not persistent at the time of nuclear imaging. The remaining sixteen
      patients exhibited a distinct pattern with HF, "apical ballooning" and a
      perfusion-metabolism defect in the midventricular/apical region. When viability
      criteria were applied, they identified significant scarring/limited hibernation
      in the akinetic part of the left ventricle. However, full recovery was found in
      all TTC patients on follow-up. Using the current guideline-endorsed viability
      criteria for semiquantitative cardiac SPECT and FDG PET, these modalities failed
      to demonstrate the presence of viability in the acute state of TTC.

PMID- 24852337
TI  - Non-invasive in vivo measurement of cardiac output in C57BL/6 mice using high
      frequency transthoracic ultrasound: evaluation of gender and body weight effects.
AB  - Even though mice are being increasingly used as models for human cardiovascular
      diseases, non-invasive monitoring of cardiovascular parameters such as cardiac
      output (CO) in this species is challenging. In most cases, the effects of gender
      and body weight (BW) on these parameters have not been studied. The objective of
      this study was to provide normal reference values for CO in C57BL/6 mice, and to
      describe possible gender and/or BW associated differences between them. We used
      30-MHz transthoracic Doppler ultrasound to measure hemodynamic parameters in the
      ascending aorta [heart rate (HR), stroke volume (SV), stroke index (SI), CO, and
      cardiac index (CI)] in ten anesthetized mice of either sex. No differences were
      found for HR, SV, and CO. Both SI and CI were statistically lower in males.
      However, after normalization for BW, these differences disappeared. These results
      suggest that if comparisons of cardiovascular parameters are to be made between
      male and female mice, values should be standardized for BW. 

PMID- 24852339
TI  - Laparoscopic versus open reversal of Hartmann's procedure: a retrospective
      review.
AB  - BACKGROUND: Restoration of bowel continuity following Hartmann's procedure may be
      performed using a laparoscopic or open technique. This study is the first of its
      kind comparing laparoscopic with open reversal of Hartmann's procedure in
      Australasia. METHODS: This is a retrospective review of 107 patients who
      underwent either a laparoscopic (n = 43) or open (n = 64) reversal of Hartmann's
      procedure between 2001 and 2012. Outcome measures were perioperative clinical
      outcomes and post-operative complications. RESULTS: Patients in the two groups
      were comparable in age, body mass index, American Society of Anesthesiologists
      score and number of previous operations. The most common indication for the
      original Hartmann's operation in both groups was diverticular disease. Total
      theatre time was longer for the laparoscopic group (276.4 versus 242.0 min; P =
      0.02). Three patients in the laparoscopic group required conversion to laparotomy
      (7%). Laparoscopic reversal of Hartmann's procedure was associated with shorter
      time to passage of flatus (2.8 versus 4.0 days; P < 0.001) and faeces (4.2 versus
      5.6 days; P = 0.002), and shorter overall length of hospital stay (6.7 versus
      10.8 days; P < 0.001). There were fewer patients in the laparoscopic group who
      had post-operative complications (14% versus 31%; P = 0.04), including fewer
      cases of post-operative ileus (2% versus 17%; P = 0.02). There were no cases of
      anastomotic leak or in-hospital mortality in either group. CONCLUSION:
      Laparoscopic reversal of Hartmann's procedure is a safe and feasible alternative
      to open Hartmann's reversal and may be associated with significantly faster
      recovery time and fewer post-operative complications.

PMID- 24852338
TI  - Left atrial appendage dysfunction in acute cerebral embolism patients with sinus
      rhythm: correlation with pulse wave tissue Doppler imaging.
AB  - To evaluate left atrial appendage (LAA) dysfunction using left atrial pulse-wave
      tissue Doppler imaging (PW-TDI) in acute cerebral embolism (ACE) patients with
      sinus rhythm (SR), transthoracic (TTE) and transesophageal echocardiograhy (TEE)
      were performed in 60 consecutive patients with SR without obvious left
      ventricular dysfunction within 2 weeks after ACE. Two groups were identified: LAA
      dysfunction [LAA emptying peak flow velocity (LAA-eV) <0.55 m/s, n = 20, age 65
      +/- 10 years] and without LAA dysfunction (LAA-eV >= 0.55 m/s, n = 40, age 64 +/-
      10 years) on TEE. Left atrial wall motion velocity (WMV) was obtained from PW
      TDI, with the sample volume placed at the left atrial anterior wall adjacent to
      ascending aortic inferior wall from the long axis view on TTE. WMVs showed
      triphasic waves: after the P wave (La') during systole (Ls'), and during early
      diastole. La' and Ls' were significantly lower in the group with versus without
      LAA dysfunction (4.9 +/- 1.4 vs. 7.7 +/- 1.8 cm/s, p < 0.0001; 5.3 +/- 2.0 vs.
      6.7 +/- 1.9 cm/s, p < 0.001, respectively) and prevalence of paroxysmal atrial
      fibrillation, left atrial volume index, and serum levels of brain natriuretic
      peptide were significantly higher (60 vs. 15 %, p < 0.001; 32 +/- 13 vs. 24 +/-
      13 ml/m(2), p < 0.05; 174 +/- 279 vs. 48 +/- 68 pg/ml, p < 0.01, respectively).
      La' was an independent predictor of LAA dysfunction (OR 0.380, 95 % CI 0.156
      0.925, p < 0.05), and was significantly correlated with LAA-eV (r = 0.594, p <
      0.0001) and LAA fractional area change (r = 0.682, p < 0.0001). The optimal cut
      off value for LAA-eV < 0.55 m/s was 5.5 cm/s (sensitivity 83 %, specificity 88
      %). La' is a useful and convenient strong predictor of LAA dysfunction in ACE
      patients with SR.

PMID- 24852340
TI  - Opening the black-box of person-centred care: An arts-informed narrative inquiry
      into mental health education and practice.
AB  - BACKGROUND: Nursing education has a history of encouraging students to know their
      patients and to negotiate the in-between of art/science, person/profession, and
      intuition/evidence. Nurse-teachers know that students may abandon some values and
      practices when they encounter practice environments that are complex and have
      competing agendas. We are concerned that nursing knowledge is black-boxed,
      invisible and taken-for-granted, in healthcare settings. OBJECTIVES: Our research
      explores how nursing students and nurses are constructing and enacting person
      centred care in mental health education and practice. We want to understand the
      nursing standpoint on this significant ontological issue and to make nursing
      knowledge construction and utilization visible; illuminating how person-centred
      theory emerges from practice. DESIGN: The process involved four 3-hour group
      meetings and an individual follow-up telephone conversation. SETTINGS: Students
      and nurses met at a tertiary-care mental health organization. PARTICIPANTS:
      Fourteen nurses (Registered Nurses and Registered Practical Nurses) and nursing
      students (Bachelor of Science in Nursing and Practical Nursing) participated in
      our inquiry. METHODS: We used arts-informed narrative inquiry to explore
      experience through the arts such as metaphor, collage, poems, letters, and group
      conversations. RESULTS: The black-box is opened as the inquiry reveals how
      nursing knowledge is constructed, assumptions are challenged and new practices
      emerge. CONCLUSIONS: Our research is significant for education and for practice
      and is transferable to other populations and settings. Nurses are affirmed in
      person-centred values and practices that include partnership with those in their
      care, role modeling for colleagues and mentoring students and new nurses.
      Students participate in transferring their learning from school to practice, in
      the company of experienced colleagues; together they open the black-box to show
      how nurses conceptualize and enact person-centred care.

PMID- 24852341
TI  - Structural similarity between beta(3)-peptides synthesized from beta(3)-homo
      amino acids and aspartic acid monomers.
AB  - Formation of stable secondary structures by oligomers that mimic natural peptides
      is a key asset for enhanced biological response. Here we show that oligomeric
      beta(3)-hexapeptides synthesized from L-aspartic acid monomers (beta(3)-peptides
      1, 5a, and 6) or homologated beta(3)-amino acids (beta(3)-peptide 2), fold into
      similar stable 14-helical secondary structures in solution, except that the
      former form right-handed 14-helix and the later form left-handed 14-helix.
      beta(3)-Peptides from L-Asp monomers contain an additional amide bond in the side
      chains that provides opportunities for more hydrogen bonding. However, based on
      the NMR solution structures, we found that beta(3)-peptide from L-Asp monomers
      (1) and from homologated amino acids (2) form similar structures with no
      additional side-chain interactions. These results suggest that the beta(3)
      peptides derived from L-Asp are promising peptide-mimetics that can be readily
      synthesized using L-Asp monomers as well as the right-handed 14-helical
      conformation of these beta(3)-peptides (such as 1 and 6) may prove beneficial in
      the design of mimics for right-handed alpha-helix of alpha-peptides.

PMID- 24852342
TI  - Seasonal variations of the humoral immune parameters of European sea bass
      (Dicentrarchus labrax L.).
AB  - Seasonal cycles, mainly due to great variations in the light duration and
      temperature, are important and modulate several aspects of the animal behavior.
      In the case of poikilotherms animals such as fish this is very relevant. Thus,
      temperature changes fish immunity and affects disease resistance. We evaluate in
      this work the season variations of the European sea bass (Dicentrarchus labrax)
      humoral innate parameters focusing on winter months, at which the culture of this
      specie is more difficult. Our results showed that not all the innate immune
      parameters are depressed by low temperatures. Moreover, some of them are more
      dependent than others to the season and both temperature and photoperiod are
      operating together. 

PMID- 24852343
TI  - Antibacterial activity and immune responses of a molluscan macrophage expressed
      gene-1 from disk abalone, Haliotis discus discus.
AB  - The membrane-attack complex/perforin (MACPF) domain-containing proteins play an
      important role in the innate immune response against invading microbial
      pathogens. In the current study, a member of the MACPF domain-containing
      proteins, macrophage expressed gene-1 (MPEG1) encoding 730 amino acids with the
      theoretical molecular mass of 79.6 kDa and an isoelectric point (pI) of 6.49 was
      characterized from disk abalone Haliotis discus discus (AbMPEG1). We found that
      the characteristic MACPF domain (Val(131)-Tyr(348)) and transmembrane segment
      (Ala(669)-Ile(691)) of AbMPEG1 are located in the N- and C-terminal ends of the
      protein, respectively. Ortholog comparison revealed that AbMPEG1 has the highest
      sequence identity with its pink abalone counterpart, while sequences identities
      of greater than 90% were observed with MPEG1 members from other abalone species.
      Likewise, the furin cleavage site KRRRK was highly conserved in all abalone
      species, but not in other species investigated. We identified an intron-less
      genomic sequence within disk abalone AbMPEG1, which was similar to other
      mammalian, avian, and reptilian counterparts. Transcription factor binding sites,
      which are important for immune responses, were identified in the 5'-flanking
      region of AbMPEG1. qPCR revealed AbMPEG1 transcripts are present in every tissues
      examined, with the highest expression level occurring in mantle tissue.
      Significant up-regulation of AbMPEG1 transcript levels was observed in hemocytes
      and gill tissues following challenges with pathogens (Vibrio parahemolyticus,
      Listeria monocytogenes and viral hemorrhagic septicemia virus) as well as
      pathogen-associated molecular patterns (PAMPs: lipopolysaccharides and poly I:C
      immunostimulant). Finally, the antibacterial activity of the MACPF domain was
      characterized against Gram-negative and -positive bacteria using a recombinant
      peptide. Taken together, these results indicate that the biological significance
      of the AbMPEG1 gene includes a role in protecting disk abalone through the
      ability of AbMPEG1 to initiate an innate immune response upon pathogen invasion.

PMID- 24852345
TI  - Combination pill effective, but expensive.

PMID- 24852344
TI  - Clathrin light chains are required for the gyrating-clathrin recycling pathway
      and thereby promote cell migration.
AB  - The clathrin light chain (CLC) subunits participate in several membrane traffic
      pathways involving both clathrin and actin, through binding the actin-organizing
      huntingtin-interacting proteins (Hip). However, CLCs are dispensable for clathrin
      mediated endocytosis of many cargoes. Here we observe that CLC depletion affects
      cell migration through Hip binding and reduces surface expression of beta1
      integrin by interference with recycling following normal endocytosis of inactive
      beta1-integrin. CLC depletion and expression of a modified CLC also inhibit the
      appearance of gyrating (G)-clathrin structures, known mediators of rapid
      recycling of transferrin receptor from endosomes. Expression of the modified CLC
      reduces beta1-integrin and transferrin receptor recycling, as well as cell
      migration, implicating G-clathrin in these processes. Supporting a physiological
      role for CLC in migration, the CLCb isoform of CLC is upregulated in migratory
      human trophoblast cells during uterine invasion. Together, these studies
      establish CLCs as mediating clathrin-actin interactions needed for recycling by G
      clathrin during migration. 

PMID- 24852346
TI  - Production, gene structure and characterization of two orthologs of leptin and a
      leptin receptor in tilapia.
AB  - Full-length cDNA encoding two leptin sequences (tLepA and tLepB) and one leptin
      receptor sequence (tLepR) were identified in tilapia (Oreochromis niloticus). The
      full-length cDNA of tLepR was 3423bp, encoding a protein of 1140 amino acid (aa)
      which contained all functionally important domains conserved among vertebrate
      leptin receptors. The cDNAs of tLepA and tLepB were 486bp and 459bp in length,
      encoding proteins of 161 aa and 152 aa, respectively. Modeling the three
      dimensional structures of tLepA and tLepB predicted strong conservation of
      tertiary structure with that of human leptin, comprised of four helixes. Using
      synteny, the tLeps were found near common genes, such as IMPDH1 and LLRC4. The
      cDNA for tLepA and tLepB was cloned and synthetic cDNA optimized for expression
      in Escherichia coli was prepared according to the cloned sequence. The tLepA- and
      tLepB-expressing plasmids were transformed into E. coli and expressed as
      recombinant proteins upon induction with nalidixic acid, found almost entirely in
      insoluble inclusion bodies (IBs). The proteins were solubilized, refolded and
      purified to homogeneity by anion-exchange chromatography. In the case of tLepA,
      the fraction eluted contained a mixture of monomers and dimers. The purified
      tLepA and tLepB monomers and tLepA dimer showed a single band of ~15kDa on an SDS
      polyacrylamide gel in the presence of reducing agent, whereas the tLepA dimer
      showed one band of ~30kDa in the absence of reducing agent, indicating its
      formation by S-S bonds. The three tLeps were biologically active in promoting
      proliferation of BAF/3 cells stably transfected with the long form of human
      leptin receptor (hLepR), but their activity was four orders of magnitude lower
      than that of mammalian leptin. Furthermore, the three tLeps were biologically
      active in promoting STAT-LUC activation in COS7 cells transfected with the
      identified tLepR but not in cells transfected with hLepR. tLepA was more active
      than tLepB. Low or no activity likely resulted from low identity (9-22%) to
      mammalian leptins. In an in vivo experiment in which tilapia were fed ad libitum
      or fasted, there was no significant difference in the expressions of tLepA, tLepB
      or tLepR in the brain between the two groups examined both by real-time PCR and
      RNA next generation sequencing. In conclusion, in the present report we show
      novel, previously unknown sequences of tilapia leptin receptor and two leptins
      and prepare two biologically active recombinant leptin proteins. 

PMID- 24852347
TI  - Leptin and cholecystokinin in Schizothorax prenanti: molecular cloning, tissue
      expression, and mRNA expression responses to periprandial changes and fasting.
AB  - In the present study, full-length cDNA sequences of leptin and cholecystokinin
      (CCK) were cloned from Schizothorax prenanti (S. prenanti), and applied real-time
      quantitative PCR to characterize the tissue distribution, and appetite regulatory
      effects of leptin and CCK in S. prenanti. The S. prenanti leptin and CCK full
      length cDNA sequences were 1121 bp and 776 bp in length, encoding the peptide of
      171 and 123 amino acid residues, respectively. Tissue distribution analysis
      showed that leptin mRNA was mainly expressed in the liver of S. prenanti. CCK was
      widely expressed, with the highest levels of expression in the hypothalamus,
      myelencephalon, telencephalon and foregut of S. prenanti. The CCK mRNA expression
      was highly elevated after feeding, whereas the leptin mRNA expression was not
      affected by single meal. These results suggested that CCK is a postprandial
      satiety signal in S. prenanti, but leptin might not be. In present study, leptin
      and CCK gene expression were both decreased after fasting and increased after
      refeeding, which suggested leptin and CCK might be involved in regulation of
      appetite in S. prenanti. This study provides an essential groundwork to further
      elucidate the appetite regulatory systems of leptin and CCK in S. prenanti as
      well as in other teleosts.

PMID- 24852348
TI  - Early expression of aromatase and the membrane estrogen receptor GPER in
      neuromasts reveals a role for estrogens in the development of the frog lateral
      line system.
AB  - Estrogens and their receptors are present at very early stages of vertebrate
      embryogenesis before gonadal tissues are formed. However, the cellular source and
      the function of estrogens in embryogenesis remain major questions in
      developmental endocrinology. We demonstrate the presence of estrogen-synthesizing
      enzyme aromatase and G protein-coupled estrogen receptor (GPER) proteins
      throughout early embryogenesis in the model organism, Silurana tropicalis. We
      provide the first evidence of aromatase in the vertebrate lateral line. High
      levels of aromatase were detected in the mantle cells of neuromasts, the
      mechanosensory units of the lateral line, which persisted throughout the course
      of development (Nieuwkoop and Faber stages 34-47). We show that GPER is expressed
      in both the accessory and hair cells. Pharmacological activation of GPER with the
      agonist G-1 disrupted neuromast development and migration. Future study of this
      novel estrogen system in the amphibian lateral line may shed light on similar
      systems such as the mammalian inner ear. 

PMID- 24852349
TI  - Elevated testosterone is required for male copulatory behavior and aggression in
      Madagascar ground gecko (Paroedura picta).
AB  - Elevated levels of gonadal androgens are often required for the expression of
      male-specific behavioral and morphological traits in all classes of vertebrates,
      including reptiles. Here, we tested the role of male gonadal androgens in the
      control of male sexual behavior, aggressive behavior, and size of the hemipenes
      in the gecko Paroedura picta. We performed hormonal manipulations involving
      castration with and without testosterone (T) replacement in males and application
      of exogenous T and ovariectomy in females. Castration suppressed sexual behavior
      and hemipenes size in males, and these effects were fully rescued by exogenous T.
      Sexual behavior and growth of the hemipenes were masculinized by male-typical
      levels of T in females, while ovariectomized females retained female-typical
      expression of these traits. These results indicate that the development of male
      sexual behavior in adult females does not require early or pubertal organization.
      Elevated T increased the likelihood of aggressive behavior directed toward a male
      intruder, but aggression occurred only rarely. Elevated T is necessary and
      sufficient for enlargement of the hemipenes and the expression of male sexual
      behavior in both males and females of Paroedura picta. In contrast to sexual
      behavior, the expression of aggressive behavior is apparently more dependent on
      other factors in addition to T itself. 

PMID- 24852350
TI  - Brain arginine vasotocin and isotocin in breeding female three-spined
      sticklebacks (Gasterosteus aculeatus): the presence of male and egg deposition.
AB  - Arginine vasotocin (AVT) and isotocin (IT) are fish hypothalamic nonapeptides
      involved in numerous social and reproductive behaviors. Vasotocinergic and
      isotocinergic fibers project to different brain areas where peptides act as
      neurotransmitters and/or neuromodulators. In this study, we measured whole brain
      levels of bioactive AVT and IT in breeding females of three-spined stickleback
      (Gasterosteus aculeatus) when they were kept with: (i) courting nest-owners, (ii)
      courting males that did not build the nest, (iii) non-courting males, and (iv)
      alone. Only some of the females kept with courting nest-owners deposited eggs.
      The highest and similar brain AVT levels were in those of females that did not
      deposit eggs, regardless of whether they were kept with non-courting or courting
      male, having the nest or not. The highest IT levels were in females that did not
      deposit eggs but only in those kept with courting male. We suggest that
      production of AVT in females' brain is stimulated by the presence of male in
      close proximity, irrespective of whether or not it displays courting behavior,
      but that of IT is stimulated by male courtship proxies. Moreover, presence of
      courting or non-courting male that stimulate IT or/and AVT producing neurones may
      be decisive for final oocyte maturation or egg deposition, because brain levels
      of both nonapeptides decrease after egg deposition. Similar AVT levels in brains
      of aggressive and non-aggressive individuals and lack of correlation between
      brain IT levels and aggressive behavior of females suggest that the nonapeptides
      are not related to females aggressiveness in three-spined sticklebacks. 

PMID- 24852351
TI  - PACAP and PAC1 receptor in the reproductive cycle of male lizard Podarcis sicula.
AB  - Pituitary adenylate cyclase-activating peptide (PACAP) is a neuropeptide involved
      in multiple functions, including vertebrate reproduction. Recently, we reported
      the presence of PACAP in the testis of Italian wall lizard Podarcis sicula during
      reproductive period (May-June). Herein we investigated the PACAP mRNA expression
      and the localization of PACAP/PACAP receptor system, in the other periods of the
      Podarcis reproductive cycle, namely in summer stasis, early autumnal resumption,
      mid-autumnal resumption, winter stasis, and spring resumption. Using biomolecular
      and immunohistochemical investigations, we demonstrated that PACAP mRNA was
      widely expressed in all germ and somatic cells; in summer stasis (July-August)
      and early autumnal resumption (September) in particular, the mRNA was always
      found in Sertoli cells while was transiently expressed in germ and in Leydig
      cells. Differently from the mRNA, the protein was always present in germ and
      somatic cells independently from the reproductive cycle phase. As PACAP, the PAC1
      receptor was always present in the testis, except for the summer stasis (July
      August) and the early autumnal resumption (September), when PACAP was lacking in
      germ and somatic cells (Leydig and Sertoli cells). The present results strongly
      suggest that PACAP/PAC1 receptor system is widely represented during the
      reproductive cycle of male lizard. The possible involvement of PACAP/PACAP
      receptor system in the control of spermatogenesis is discussed. 

PMID- 24852352
TI  - Immune responses of eastern fence lizards (Sceloporus undulatus) to repeated
      acute elevation of corticosterone.
AB  - Prolonged elevations of glucocorticoids due to long-duration (chronic) stress can
      suppress immune function. It is unclear, however, how natural stressors that
      result in repeated short-duration (acute) stress, such as frequent agonistic
      social encounters or predator attacks, fit into our current understanding of the
      immune consequences of stress. Since these types of stressors may activate the
      immune system due to increased risk of injury, immune suppression may be reduced
      at sites where individuals are repeatedly exposed to potentially damaging
      stressors. We tested whether repeated acute elevation of corticosterone (CORT, a
      glucocorticoid) suppresses immune function in eastern fence lizards (Sceloporus
      undulatus), and whether this effect varies between lizards from high-stress (high
      baseline CORT, invaded by predatory fire ants) and low-stress (low baseline CORT,
      uninvaded) sites. Lizards treated daily with exogenous CORT showed higher
      hemagglutination of novel proteins by their plasma (a test of constitutive
      humoral immunity) than control lizards, a pattern that was consistent across
      sites. There was no significant effect of CORT treatment on bacterial killing
      ability of plasma. These results suggest that repeated elevations of CORT, which
      are common in nature, produce immune effects more typical of those expected at
      the acute end of the acute-chronic spectrum and provide no evidence of modulated
      consequences of elevated CORT in animals from high-stress sites. 

PMID- 24852353
TI  - Molecular characterization and analysis of a putative 5-HT receptor involved in
      reproduction process of the pearl oyster Pinctada fucata.
AB  - 5-HT (5-hydroxytryptamine; serotonin) has been linked to a variety of biological
      roles including gonad maturation and sequential spawning in bivalve molluscs. To
      gain a better understanding of the effects of 5-HT on developmental regulation in
      the pearl oyster Pinctada fucata, the isolation, cloning, and expression of the 5
      HT receptor was investigated in this study. A full-length cDNA (2541 bp) encoding
      a putative 5-HT receptor (5-HTpf) of 471 amino acids was isolated from the ovary
      of the pearl oyster. It shared 71% and 51% homology, respectively, with the
      Crassostrea gigas 5-HT receptor and the Aplysia californica 5-HT1ap. The 5-HTpf
      sequence possessed the typical characteristics of seven transmembrane domains and
      a long third inner loop. Phylogenetic analysis also indicated that 5-HTpf was
      classified into the 5-HT1 subtype together with other invertebrate 5-HT1
      receptors. Quantitative RT-PCR showed that 5-HTpf is widely expressed in all
      tissues tested, is involved in the gametogenesis cycle, embryonic and larval
      development stages, and expression is induced by E2 in ovarian tissues. These
      results suggest that 5-HTpf is involved in the reproductive process, specifically
      in the induction of oocyte maturation and spawning of P. fucata.

PMID- 24852354
TI  - Recombinant interleukin-12, but not granulocyte-colony stimulating factor,
      improves survival in lethally irradiated nonhuman primates in the absence of
      supportive care: evidence for the development of a frontline radiation medical
      countermeasure.
AB  - Hematopoietic syndrome of acute radiation syndrome (HSARS) is a life-threatening
      condition with no approved treatment. We compared recombinant human interleukin
      12 (rHuIL-12; 175 ng/kg * 1) with vehicle, granulocyte-colony-stimulating factor
      (G-CSF; 10 ug/kg/day * 18), or rHuIL-12+G-CSF after lethal irradiation in rhesus
      monkeys in a Good Laboratory Practice, randomized, blinded, placebo-controlled
      study. Fluids, antibiotics, and blood products were not used. Survival at day 60
      was significantly increased for rHuIL-12 versus G-CSF or vehicle. rHuIL-12/G-CSF
      combination provided no additional survival benefit over rHuIL-12. Both rHuIL-12
      and rHuIL-12+G-CSF increased blood cell nadirs, induced earlier recovery of all
      hematopoietic lineages, and significantly decreased frequencies of severe
      cytopenias versus vehicle or G-CSF. In bone marrow, rHuIL-12 alone increased
      erythroid, myeloid, and megakaryocyte counts relative to vehicle or G-CSF. Thus,
      a single injection of rHuIL-12, without supportive medical intervention,
      significantly improved survival and promoted multilineage hematopoietic recovery
      in a nonhuman primate model of HSARS.

PMID- 24852355
TI  - Modulatory effects of sodium salicylate on the factors affecting protein
      aggregation during rotenone induced Parkinson's disease pathology.
AB  - Sodium salicylate (SS) confers neuroprotection in various models of Parkinson's
      disease (PD) but the mechanisms behind its protective actions are not clear. PD
      pathology is multifactorial involving numerous processes such as protein
      aggregation, dysfunction of protein degradation machinery and apoptosis. Detailed
      evaluation of effects of SS on these processes can provide an insight into the
      mechanism of neuroprotection by SS in PD pathology. In a rotenone (2mg/kg b.w.)
      based rat model of PD, SS (100mg/kg b.w.) was administered in conjunction. Drug
      treatments continued for 5 weeks after which various analyses were conducted
      using mid-brain tissue. IHC analysis revealed a decline in the aggregation of
      alpha-synuclein and ubiquitin with SS supplementation. These effects might be
      mediated by the elevation in HSF-1, HSP-40, and HSP-27 expression following SS co
      treatment. This HSP upregulation helped in the improvement in proteasome activity
      as well as expression. Further, IHC analysis revealed that SS co-treatment
      prevented the activation of astrocytes caused by rotenone. Since astrocytes are
      involved in maintenance of glutathione (GSH) homeostasis, it resulted in a
      concomitant improvement in the GSH levels. As a result, decrease in apoptosis as
      indicated by caspase-9 and caspase-3 expression as well as TUNEL assay was also
      observed in the SS conjunction group. Our results indicate that besides being a
      known free radical scavenger and anti-inflammatory compound, SS can provide
      neuroprotection by differently upregulating the HSPs and reducing the protein
      aggregation burden.

PMID- 24852356
TI  - Distributed observers for pose estimation in the presence of inertial sensory
      soft faults.
AB  - Distributed Particle-Kalman Filter based observers are designed in this paper for
      inertial sensors (gyroscope and accelerometer) soft faults (biases and drifts)
      and rigid body pose estimation. The observers fuse inertial sensors with
      Photogrammetric camera. Linear and angular accelerations as unknown inputs of
      velocity and attitude rate dynamics, respectively, along with sensory biases and
      drifts are modeled and augmented to the moving body state parameters. To reduce
      the complexity of the high dimensional and nonlinear model, the graph theoretic
      tearing technique (structural decomposition) is employed to decompose the system
      to smaller observable subsystems. Separate interacting observers are designed for
      the subsystems which are interacted through well-defined interfaces. Kalman
      Filters are employed for linear ones and a Modified Particle Filter for a
      nonlinear non-Gaussian subsystem which includes imperfect attitude rate dynamics
      is proposed. The main idea behind the proposed Modified Particle Filtering
      approach is to engage both system and measurement models in the particle
      generation process. Experimental results based on data from a 3D MEMS IMU and a
      3D camera system are used to demonstrate the efficiency of the method. 

PMID- 24852357
TI  - Predictors of using mental health services after sexual assault.
AB  - Sexual assault increases the risk for psychopathology. Despite the availability
      of effective interventions, relatively few victims who need treatment receive
      care in the months following an assault. Prior work identified several factors
      associated with utilizing care, including ethnicity, insurance, and posttraumatic
      stress disorder (PTSD) symptoms. Few studies, however, have examined predictors
      of treatment utilization prospectively from the time of assault. The present
      study hypothesized that White racial status, younger age, being partnered, having
      health insurance, having previously received mental health treatment, and having
      more PTSD and depression symptoms would predict utilization of care in the 6
      months postassault. This was examined in a sample of 266 female sexual assault
      victims with an average age of 26.2 years, of whom 62.0% were White and 38.0%
      were African American assessed at 1.5 and 6 months postassault. Available
      information on utilizing care varied across assessments (1.5 months, n = 214; 3
      months, n = 126; 6 months, n = 204). Significant predictors included having
      previously received mental health treatment (OR = 4.09), 1 day depressive
      symptoms (OR = 1.06), and having private insurance (OR = 2.24) or Medicaid (OR =
      2.19). Alcohol abuse and prior mental health care were associated with a
      substantial increase in treatment utilization (OR = 4.07). The findings highlight
      the need to help victims at risk obtain treatment after sexual assault. 

PMID- 24852358
TI  - The transcriptional repression activity of STAF65gamma is facilitated by promoter
      tethering and nuclear import of class IIa histone deacetylases.
AB  - Aberrant expression levels of transcriptional regulators result in alterations in
      transcriptional control. STAF65gamma is a structural subunit of the GCN5
      transcriptional co-activator complex. Reports showed that STAF65gamma is highly
      expressed in several human cancer cells, but the consequences of this aberrant
      expression pattern remain elusive. Here, we show that the STAF65gamma protein is
      highly expressed in lung adenocarcinoma patients and high levels of STAF65gamma
      correlate with poor prognosis. High levels of STAF65gamma cause repression of the
      c-Myc oncogene through physical association with transcription factor YY1 and co
      repressors HDACs. Physical interactions between STAF65gamma and class IIa HDACs
      facilitate nuclear enrichment and regulate the assembly of HDAC complexes.
      Moreover, SUMOylation of STAF65gamma is necessary for maintaining the co
      repressor complex containing YY1 and class IIa HDACs at the promoter. Our
      findings reveal a distinct role of STAF65gamma in nuclear import, transcriptional
      repression, and cell cycle regulation at high levels of expression, which is
      associated with poor clinical outcomes of lung adenocarcinoma. 

PMID- 24852359
TI  - HCC prevalence and histopathological findings in liver explants of patients with
      hereditary tyrosinemia type 1.
AB  - BACKGROUND: Untreated tyrosinemia type 1 (HT1) is manifested by liver failure
      associated with renal tubular dysfunction, growth failure, and rickets. The
      indication for liver transplantation (LT) is restricted to non-responders to 2-(2
      nitro-4-trifluoromethylbenzoyl)-1, 3-cyclohexanedione (NTBC) treatment, patients
      not treated with NTBC or for patients with HCC. The aim of this study is to
      report on a series of NTBC naive HT1 patients submitted to LT along with the
      prevalence of HCC in their liver explants. PROCEDURE: This is a retrospective
      study of 16 children with HT1 who underwent liver transplantation between January
      1993 and December 2012. RESULTS:  CLINICAL FEATURES: liver failure in 12 (75%),
      growth failure in 4 (25%), rickets in 5 (31.2%), hypertrophic cardiomyopathy in
      three (18.7%), and renal tubulopathy in seven patients (43.7%). Median AFP level
      was 64,335 ng/ml. Abdominal CT scans showed multiple nodules in most patients.
      Histopathology of the explants showed cirrhosis in all patients and HCC in 12
      (75%), 3 with microvascular invasion. The majority of the tumors were well
      differentiated. Patient survival rate was 86% at a median follow-up of 6.6 years.
      All survivors were tumor-free with no adjuvant chemotherapy. CONCLUSION: In
      countries where neonatal screening programs are not effective and NTBC treatment
      is not widely available, LT still plays an important role in the treatment of
      children with HT1. An early indication in patients who present with multinodular
      livers can also serve to treat an otherwise underdiagnosed HCC condition.

PMID- 24852361
TI  - Patient autonomy as a limit on a doctor's duty to follow-up.
AB  - The principle of personal autonomy means that patients are free not to attend
      scheduled medical appointments and to risk the complications that may occur as a
      consequence of their non-attendance. But the situation may be more complicated if
      the patient's doctor recognises that the patient may be vulnerable to a
      particular risk. What are the limits of the doctor's obligation to follow-up or
      recall the patient for a further consultation? Some recent cases cast light upon
      this issue.

PMID- 24852360
TI  - Eribulin mesylate in the management of metastatic breast cancer and other solid
      cancers: a drug review.
AB  - In the new era of 'precision' cancer medicine, new drug development has shifted
      from cytotoxic chemotherapy to molecularly targeted agents. Eribulin mesylate, a
      microtubule-destabilizing agent, is the only 'classical' cytotoxic agent approved
      for the treatment of breast cancer in the last 7 years. This synthetic analogue
      of halichondrin B, isolated from the marine sponge 'Halicondria Okaida', was
      responsible for prolonging overall survival of heavily pretreated metastatic
      breast cancer patients in a large Phase III trial. Eribulin is now under clinical
      development in earlier settings such as the neo-adjuvant and adjuvant settings.
      Furthermore, its unique mechanism of action and the absence of cross-resistance
      with taxanes have led to the design of clinical trials in multiple indications:
      bladder cancer, lung cancer, prostate cancer... The main adverse events are
      neutropenia, fatigue and peripheral neuropathy.

PMID- 24852362
TI  - E-suicide note: A newer trend and its medico-legal implications in India.
AB  - Rapid advancements of information and communication technology in the form of
      electronic mails, mobile phones, social networking sites, etc have an increasing
      impact on people's day to day life. It has been observed that these readily
      available applications are used frequently to express suicidal intentions. There
      are many studies on conventional handwritten suicide notes but suicide note in
      electronic format is an emerging issue and an under-researched phenomena. The
      authors have termed it as "E-suicide note" and discuss its medico-legal
      implications in India with examples from their observations.

PMID- 24852363
TI  - Castration laws: Marching towards imperfect justice.
AB  - Castration is an anthropogenic procedure by which the person loses the functions
      of the testicles or ovaries; it can be performed by surgery or by administering
      chemicals. The motivation was primarily eugenic, to weed out the "unfit" from the
      human gene pool. In 1996, California first introduced chemical castration under s
      645 of the California Penal Code for child molestation and this legal template
      has spread globally to counter sexual offences. The anti-androgenic
      pharmacotherapy used for chemical castration includes cyproterone acetate or
      medroxy-progesterone acetate (Depo-Provera), which reduces testosterone levels
      and reduces male sexual urge and fantasies. However, the associated health
      hazards with anti-libido drugs put a question mark on such State sponsored penal
      response. Castration destroys human dignity, breaches the right of privacy and
      procreation and attracts the cruel and unusual punishment clause. The failed
      Oregon castration experiment and Moldova Court verdict in July 2013 indicate that
      the stage is set to right this wrong.

PMID- 24852364
TI  - Alcohol, duty-of-care and common law--where do the consequences of drunken
      behaviour lie?
AB  - Legal issues around the duty of care in common law with regard to addictive legal
      drugs are evolving. Two recent cases came before the Irish courts dealing with
      the issue of duty of care of alcohol suppliers to intoxicated individuals. In
      both cases the intoxication was self-induced and the consequences were lethal.
      The juxtaposition of personal autonomy and duty of care cannot ignore personal
      responsibility. Do we need protection from ourselves? 

PMID- 24852365
TI  - Fetal MRI diagnosis of brainstem disconnection with novel inner ear anomalies.

PMID- 24852366
TI  - Effects of externally supplied protein on root morphology and biomass allocation
      in Arabidopsis.
AB  - Growth, morphogenesis and function of roots are influenced by the concentration
      and form of nutrients present in soils, including low molecular mass inorganic N
      (IN, ammonium, nitrate) and organic N (ON, e.g. amino acids). Proteins, ON of
      high molecular mass, are prevalent in soils but their possible effects on roots
      have received little attention. Here, we investigated how externally supplied
      protein of a size typical of soluble soil proteins influences root development of
      axenically grown Arabidopsis. Addition of low to intermediate concentrations of
      protein (bovine serum albumen, BSA) to IN-replete growth medium increased root
      dry weight, root length and thickness, and root hair length. Supply of higher BSA
      concentrations inhibited root development. These effects were independent of
      total N concentrations in the growth medium. The possible involvement of
      phytohormones was investigated using Arabidopsis with defective auxin (tir1-1 and
      axr2-1) and ethylene (ein2-1) responses. That no phenotype was observed suggests
      a signalling pathway is operating independent of auxin and ethylene responses.
      This study expands the knowledge on N form-explicit responses to demonstrate that
      ON of high molecular mass elicits specific responses. 

PMID- 24852368
TI  - NIM811, a cyclophilin inhibitor without immunosuppressive activity, is beneficial
      in collagen VI congenital muscular dystrophy models.
AB  - Ullrich congenital muscular dystrophy (UCMD) and Bethlem myopathy (BM) are
      inherited muscle diseases due to mutations in the genes encoding the
      extracellular matrix protein collagen (Col) VI. Opening of the cyclosporin A
      sensitive mitochondrial permeability transition pore (PTP) is a causative event
      in disease pathogenesis, and a potential target for therapy. Here, we have tested
      the effect of N-methyl-4-isoleucine-cyclosporin (NIM811), a non-immunosuppressive
      cyclophilin inhibitor, in a zebrafish model of ColVI myopathy obtained by
      deletion of the N-terminal region of the ColVI alpha1 triple helical domain, a
      common mutation of UCMD. Treatment with antisense morpholino sequences targeting
      col6a1 exon 9 at the 1-4 cell stage (within 1 h post fertilization, hpf) caused
      severe ultrastructural and motor abnormalities as assessed by electron and
      fluorescence microscopy, birefringence, spontaneous coiling events and touch
      evoked responses measured at 24-48 hpf. Structural and functional abnormalities
      were largely prevented when NIM811--which proved significantly more effective
      than cyclosporin A--was administered at 21 hpf, while FK506 was ineffective.
      Beneficial effects of NIM811 were also detected (i) in primary muscle-derived
      cell cultures from UCMD and BM patients, where the typical mitochondrial
      alterations and depolarizing response to rotenone and oligomycin were
      significantly reduced; and (ii) in the Col6a1(-/-) myopathic mouse model, where
      apoptosis was prevented and muscle strength was increased. Since the PTP of
      zebrafish shares its key regulatory features with the mammalian pore, our results
      suggest that early treatment with NIM811 should be tested as a potential therapy
      for UCMD and BM.

PMID- 24852369
TI  - Atmin mediates kidney morphogenesis by modulating Wnt signaling.
AB  - The DNA damage protein and transcription factor Atmin (Asciz) is required for
      both lung tubulogenesis and ciliogenesis. Like the lungs, kidneys contain a
      tubular network that is critical for their function and in addition, renal
      ciliary dysfunction has been implicated in the pathogenesis of cystic kidney
      disease. Using the Atmin mouse mutant Gasping6 (Gpg6), we investigated kidney
      development and found it severely disrupted with reduced branching morphogenesis,
      resulting in fewer epithelial structures being formed. Unexpectedly,
      transcriptional levels of key cilia associated genes were not altered in
      Atmin(Gpg6/Gpg6) kidneys. Instead, Gpg6 homozygous kidneys exhibited altered
      cytoskeletal organization and modulation of Wnt signaling pathway molecules,
      including beta-catenin and non-canonical Wnt/planar cell polarity (PCP) pathway
      factors, such as Daam2 and Vangl2. Wnt signaling is important for kidney
      development and perturbation of Wnt signaling pathways can result in cystic, and
      other, renal abnormalities. In common with other PCP pathway mutants,
      Atmin(Gpg6/Gpg6) mice displayed a shortened rostral-caudal axis and mis-oriented
      cell division. Moreover, intercrosses between Atmin(Gpg6/+) and Vangl2(Lp/+) mice
      revealed a genetic interaction between Atmin and Vangl2. Thus we show for the
      first time that Atmin is critical for normal kidney development and we present
      evidence that mechanistically, Atmin modifies Wnt signaling pathways,
      specifically placing it as a novel effector molecule in the non-canonical Wnt/PCP
      pathway. The identification of a novel modulator of Wnt signaling has important
      implications for understanding the pathobiology of renal disease. 

PMID- 24852367
TI  - Genome-wide association study and mouse expression data identify a highly
      conserved 32 kb intergenic region between WNT3 and WNT9b as possible
      susceptibility locus for isolated classic exstrophy of the bladder.
AB  - Bladder exstrophy-epispadias complex (BEEC), the severe end of the urorectal
      malformation spectrum, has a profound impact on continence as well as sexual and
      renal functions. It is widely accepted that for the majority of cases the genetic
      basis appears to be multifactorial. Here, we report the first study which
      utilizes genome-wide association methods to analyze a cohort comprising patients
      presenting the most common BEEC form, classic bladder exstrophy (CBE), to
      identify common variation associated with risk for isolated CBE. We employed
      discovery and follow-up samples comprising 218 cases/865 controls and 78 trios in
      total, all of European descent. Our discovery sample identified a marker near
      SALL1, showing genome-wide significant association with CBE. However, analyses
      performed on follow-up samples did not add further support to these findings. We
      were also able to identify an association with CBE across our study samples
      (discovery: P = 8.88 * 10(-5); follow-up: P = 0.0025; combined: 1.09 * 10(-6)) in
      a highly conserved 32 kb intergenic region containing regulatory elements between
      WNT3 and WNT9B. Subsequent analyses in mice revealed expression for both genes in
      the genital region during stages relevant to the development of CBE in humans.
      Unfortunately, we were not able to replicate the suggestive signal for WNT3 and
      WNT9B in a sample that was enriched for non-CBE BEEC cases (P = 0.51). Our
      suggestive findings support the hypothesis that larger samples are warranted to
      identify association of common variation with CBE. 

PMID- 24852370
TI  - Genome-wide association study identifies a novel susceptibility gene for serum
      TSH levels in Chinese populations.
AB  - Thyroid-stimulating hormone (TSH) is a sensitive indicator of thyroid function.
      High and low TSH levels reflect hypothyroidism and hyperthyroidism, respectively.
      Even within the normal range, small differences in TSH levels, on the order of
      0.5-1.0 mU/l, are associated with significant differences in blood pressure, BMI,
      dyslipidemia, risk of atrial fibrillation and atherosclerosis. Most of the
      variance in TSH levels is thought to be genetically influenced. We conducted a
      genome-wide association study of TSH levels in 1346 Chinese Han individuals. In
      the replication study, we genotyped four candidate SNPs with the top association
      signals in an independent isolated Chinese She cohort (n = 3235). We identified a
      novel serum TSH susceptibility locus within XKR4 at 8q12.1 (rs2622590, Pcombined
      = 2.21 * 10(-10)), and we confirmed two previously reported TSH susceptibility
      loci near FOXE1 at 9q22.33 and near CAPZB at 1p36.13, respectively. The
      rs2622590_T allele at XKR4 and the rs925489_C allele near FOXE1 were correlated
      with low TSH levels and were found to be nominally associated to patients with
      papillary thyroid carcinoma (PTC) (OR = 1.41, P= 0.014 for rs2622590_T, and OR =
      1.61, P= 0.030 for rs925489_C). The rs2622590 and rs925489 genotypes were also
      correlated with the expression levels of FOXE1 and XKR4, respectively, in PTC
      tissues (P = 2.41 * 10(-4) and P= 0.02). Our findings suggest that the SNPs in
      XKR4 and near FOXE1 are involved in the regulation of TSH levels. 

PMID- 24852371
TI  - The deubiquitinase USP15 antagonizes Parkin-mediated mitochondrial ubiquitination
      and mitophagy.
AB  - Loss-of-function mutations in PARK2, the gene encoding the E3 ubiquitin ligase
      Parkin, are the most frequent cause of recessive Parkinson's disease (PD). Parkin
      translocates from the cytosol to depolarized mitochondria, ubiquitinates outer
      mitochondrial membrane proteins and induces selective autophagy of the damaged
      mitochondria (mitophagy). Here, we show that ubiquitin-specific protease 15
      (USP15), a deubiquitinating enzyme (DUB) widely expressed in brain and other
      organs, opposes Parkin-mediated mitophagy, while a panel of other DUBs and a
      catalytically inactive version of USP15 do not. Moreover, knockdown of USP15
      rescues the mitophagy defect of PD patient fibroblasts with PARK2 mutations and
      decreased Parkin levels. USP15 does not affect the ubiquitination status of
      Parkin or Parkin translocation to mitochondria, but counteracts Parkin-mediated
      mitochondrial ubiquitination. Knockdown of the DUB CG8334, the closest homolog of
      USP15 in Drosophila, largely rescues the mitochondrial and behavioral defects of
      parkin RNAi flies. These data identify USP15 as an antagonist of Parkin and
      suggest that USP15 inhibition could be a therapeutic strategy for PD cases caused
      by reduced Parkin levels. 

PMID- 24852372
TI  - STRA6 is critical for cellular vitamin A uptake and homeostasis.
AB  - Vitamin A must be adequately distributed within the body to maintain the
      functions of retinoids in the periphery and chromophore production in the eyes.
      Blood transport of the lipophilic vitamin is mediated by the retinol-binding
      protein, RBP4. Biochemical evidence suggests that cellular uptake of vitamin A
      from RBP4 is facilitated by a membrane receptor. This receptor, identified as the
      Stimulated by retinoic acid gene 6 (Stra6) gene product, is highly expressed in
      epithelia that constitute blood-tissue barriers. Here we established a Stra6
      knockout mouse model to analyze the metabolic basis of vitamin A homeostasis in
      peripheral tissues. These mice were viable when bred on diets replete in vitamin
      A, but evidenced markedly reduced levels of ocular retinoids. Ophthalmic imaging
      and histology revealed malformations in the choroid and retinal pigmented
      epithelium, early cone photoreceptor cell death, and reduced lengths of rod outer
      segments. Similar to the blood-retina barrier in the RPE, vitamin A transport
      through the blood-cerebrospinal fluid barrier in the brain's choroid plexus was
      impaired. Notably, treatment with pharmacological doses of vitamin A restored
      vitamin A transport across these barriers and rescued the vision of Stra6(-/-)
      mice. Furthermore, under conditions mimicking vitamin A excess and deficiency,
      our analyses revealed that STRA6-mediated vitamin A uptake is a regulated process
      mandatory for ocular vitamin A uptake when RBP4 constitutes the only transport
      mode in vitamin A deficiency. These findings identifying STRA6 as a bona fide
      vitamin A transporter have important implications for disease states associated
      with impaired blood vitamin A homeostasis. 

PMID- 24852374
TI  - Gene dosage of the transcription factor Fingerin (bHLHA9) affects digit
      development and links syndactyly to ectrodactyly.
AB  - Distal limb deformities are congenital malformations with phenotypic variability,
      genetic heterogeneity and complex inheritance. Among these, split-hand/foot
      malformation is an ectrodactyly with missing central fingers, yielding a lobster
      claw-like hand, which when combined with long-bone deficiency is defined as split
      hand/foot malformation and long-bone deficiency (SHFLD) that is genetically
      heterogeneous. Copy number variation (CNV) consisting of 17p13.3 duplication was
      identified in unrelated pedigrees, underlying SHFLD3 (OMIM 612576). Although the
      transcription factor Fingerin (bHLHA9) is the only complete gene in the critical
      region, its biological role is not yet known and there are no data supporting its
      involvement in mammalian limb development. We have generated knockout mice in
      which only the entire coding region of Fingerin was deleted, and indeed found
      that most null mice display some limb defects. These include various levels of
      simple asymmetrical syndactyly, characterized by webbed fingers, generated by
      incomplete separation of soft, but not skeletal, tissues between forelimb digits
      2 and 3. As expected, hand pads of Fingerin null embryos exhibited reduced
      apoptosis between digital rays 2 and 3. This defect was shown to cause syndactyly
      when the same limbs were grown ex vivo following the apoptosis assay.
      Extrapolating from mouse data, we suggest that Fingerin loss-of-function in
      humans may underlie MSSD syndactyly (OMIM 609432), which was mapped to the same
      locus. Taken together, Fingerin gene dosage links two different congenital limb
      malformations, syndactyly and ectrodactyly, which were previously postulated to
      share a common etiology. These results add limb disorders to the growing list of
      diseases resulting from CNV. 

PMID- 24852373
TI  - ACVR1 p.Q207E causes classic fibrodysplasia ossificans progressiva and is
      functionally distinct from the engineered constitutively active ACVR1 p.Q207D
      variant.
AB  - Fibrodysplasia ossificans progressiva (FOP) is a disabling genetic disorder of
      progressive heterotopic ossification (HO). Here, we report a patient with an
      ultra-rare point mutation [c.619C>G, p.Q207E] located in a codon adjacent to the
      most common FOP mutation [c.617G>A, p.R206H] of Activin A Receptor, type 1
      (ACVR1) and that affects the same intracellular amino acid position in the GS
      activation domain as the engineered constitutively active (c.a.) variant p.Q207D.
      It was predicted that both mutations at residue 207 have similar functional
      effects by introducing a negative charge. Transgenic p.Q207D-c.a. mice have
      served as a model for FOP HO in several in vivo studies. However, we found that
      the engineered ACVR1(Q207D-c.a.) is significantly more active than the classic
      FOP mutation ACVR1(R206H) when overexpressed in chicken limbs and in
      differentiation assays of chondrogenesis, osteogenesis and myogenesis.
      Importantly, our studies reveal that the ACVR1(Q207E) resembles the classic FOP
      receptor in these assays, not the engineered ACVR1(Q207D-c.a.). Notably, reporter
      gene assays revealed that both naturally occurring FOP receptors (ACVR1(R206H)
      and ACVR1(Q207E)) were activated by BMP7 and were sensitive to deletion of the
      ligand binding domain, whereas the engineered ACVR1(Q207D-c.a.) exhibited ligand
      independent activity. We performed an in silico analysis and propose a structural
      model for p.Q207D-c.a. that irreversibly relocates the GS domain into an
      activating position, where it becomes ligand independent. We conclude that the
      engineered p.Q207D-c.a. mutation has severe limitations as a model for FOP,
      whereas the naturally occurring mutations p.R206H and p.Q207E facilitate receptor
      activation, albeit in a reversible manner. 

PMID- 24852377
TI  - Fighting influenza--a new weapon in the armoury?

PMID- 24852376
TI  - Effect of nitazoxanide in adults and adolescents with acute uncomplicated
      influenza: a double-blind, randomised, placebo-controlled, phase 2b/3 trial.
AB  - BACKGROUND: Influenza is an important cause of morbidity and mortality worldwide.
      Treatment options are scarce, and new drugs with novel mechanisms of action are
      needed. We aimed to assess the efficacy and safety of nitazoxanide, a thiazolide
      anti-infective, for treatment of acute uncomplicated influenza. METHODS: We did a
      double-blind, randomised, placebo-controlled, phase 2b/3 trial in 74 primary care
      clinics in the USA between Dec 27, 2010, and April 30, 2011. We enrolled
      participants aged 12-65 years with fever, at least one respiratory symptom, and
      one constitutional symptom of influenza within 48 h of symptom onset. We randomly
      assigned participants to receive either nitazoxanide 600 mg, nitazoxanide 300 mg,
      or placebo twice daily for 5 days, (ratio 1:1:1) and followed them up for 28
      days. Randomisation lists were computer generated and done in blocks of three.
      Sponsor, investigators, study monitors, patients, and laboratory personnel were
      all masked to treatment allocation in the study. The primary endpoint was the
      time from first dose to alleviation of symptoms. The primary analysis was by
      intention-to-treat for participants with influenza infection confirmed by RT-PCR
      or culture at baseline. This trial is registered with ClinicalTrials.gov, number
      NCT01227421. FINDINGS: Of 650 participants screened, 624 (96%) were enrolled. Of
      these, 212 were randomly assigned to receive placebo twice a day, 201 to receive
      nitazoxanide 300 mg twice a day, and 211 to receive nitazoxanide 600 mg a day.
      The median duration of symptoms for participants receiving placebo was 116.7 h
      (95% CI 108.1-122.1) compared with 95.5 h (84.0-108.0; p=0.0084) for those
      receiving 600 mg nitazoxanide and 109.1 h (96.1-129.5, p=0.52) for those
      receiving 300 mg nitazoxanide. Adverse events were similar between the three
      groups, the most common being headache reported by 24 (11%) of 212 patients
      enrolled in placebo group, 12 (6%) of 201 patients in the low-dose group, and 17
      (8%) of 211 patients in the high-dose group, or diarrhoea, reported by seven (3%)
      patients in the placebo group, four (2%) patients enrolled in the low-dose group,
      and 17 (8%) patients in the high-dose group. INTERPRETATION: Treatment with
      nitazoxanide 600 mg twice daily for 5 days was associated with a reduction of the
      duration of symptoms in participants with acute uncomplicated influenza. Further
      studies are warranted to confirm these findings and to assess efficacy of the
      drug alone or in combination with existing drugs in seriously ill patients and
      those at risk of influenza complications. FUNDING: Romark Laboratories LC.

PMID- 24852378
TI  - [Non-invasive ventilation improves comfort in pediatric palliative care
      patients].
AB  - OBJECTIVE: To analyze the appropriate use of non-invasive ventilation and its
      contribution to improving comfort in pediatric palliative care patients. PATIENTS
      AND METHOD: This is a descriptive cross-sectional study comprising 55 palliative
      care patients from San Juan de Dios Hospital in Barcelona. The effectiveness was
      evaluated using a register of socio-demographic, clinical-ventilatory and
      oxymetric parameters, the comfort and dyspnea's grade using Silverman Anderson
      scale, and pain level using pediatric scales. RESULTS: The effectiveness of the
      technique was proved by a decreased heart rate (133.53+/-25.8 vs. 111.04+/-23.1;
      p<0.0001), respiratory rate (35.02+/-12.9 vs. 25.63+/-5.7; p<0.0001) and an
      increase of partial oxygen saturation (95.7+/-2.9 vs. 96.87+/-7.2; p<0.0001) and
      partial oxygen saturation/fraction of inspired oxygen ratio (297.12+/-113.4 vs.
      336.97+/-100.7; p<0.0001). Dyspnea and pain levels improved in 100% of the
      patients. CONCLUSIONS: The therapy was effective and the comfort improved in 100%
      of the patients.

PMID- 24852375
TI  - A comprehensive examination of breast cancer risk loci in African American women.
AB  - Genome-wide association studies have identified 73 breast cancer risk variants
      mainly in European populations. Given considerable differences in linkage
      disequilibrium structure between populations of European and African ancestry,
      the known risk variants may not be informative for risk in African ancestry
      populations. In a previous fine-mapping investigation of 19 breast cancer loci,
      we were able to identify SNPs in four regions that better captured risk
      associations in African American women. In this study of breast cancer in African
      American women (3016 cases, 2745 controls), we tested an additional 54 novel
      breast cancer risk variants. Thirty-eight variants (70%) were found to have an
      association with breast cancer in the same direction as previously reported, with
      eight (15%) replicating at P < 0.05. Through fine-mapping, in three regions
      (1q32, 3p24, 10q25), we identified variants that better captured associations
      with overall breast cancer or estrogen receptor positive disease. We also
      observed suggestive associations with variants (at P < 5 * 10(-6)) in three
      separate regions (6q25, 14q13, 22q12) that may represent novel risk variants.
      Directional consistency of association observed for ~65-70% of currently known
      genetic variants for breast cancer in women of African ancestry implies a shared
      functional common variant at most loci. To validate and enhance the spectrum of
      alleles that define associations at the known breast cancer risk loci, as well as
      genome-wide, will require even larger collaborative efforts in women of African
      ancestry. 

PMID- 24852381
TI  - Tumor thrombus in the renal vein from an adrenal metastasis of lung cancer: 18FDG
      PET/CT findings.
AB  - Tumor thrombus is a rare complication of solid cancer. The authors report a case
      of a 76-year-old woman presenting a thick walled cystic mass in the lower lobe of
      the left lung. 18FDG positron emission tomography (PET)/computed tomography (CT)
      was performed, showing tracer accumulation in the wall of the pulmonary lesion
      and in the mediastinal and hilar lymph nodes. Moreover, PET/CT depicted a gross
      mass in the left adrenal gland and a hypermetabolic focus corresponding to the
      anatomic location of the left renal vein. Contrast-enhanced CT, subsequently
      performed, confirmed PET findings in the lung, lymph nodes, and adrenal glands,
      also demonstrating marginal enhancement and intraluminal filling defect in the
      left renal vein, which was interpreted as tumor thrombus due to the 18FDG uptake
      at PET scan. CT-guided biopsy of the mass was positive for poorly differentiated
      carcinoma. 18FDG PET can be useful to diagnose tumor thrombus in oncological
      patients.

PMID- 24852379
TI  - The mucoid switch in Pseudomonas aeruginosa represses quorum sensing systems and
      leads to complex changes to stationary phase virulence factor regulation.
AB  - The opportunistic pathogen Pseudomonas aeruginosa chronically infects the airways
      of Cystic Fibrosis (CF) patients during which it adapts and undergoes clonal
      expansion within the lung. It commonly acquires inactivating mutations of the
      anti-sigma factor MucA leading to a mucoid phenotype, caused by excessive
      production of the extracellular polysaccharide alginate that is associated with a
      decline in lung function. Alginate production is believed to be the key benefit
      of mucA mutations to the bacterium in the CF lung. A phenotypic and gene
      expression characterisation of the stationary phase physiology of mucA22 mutants
      demonstrated complex and subtle changes in virulence factor production, including
      cyanide and pyocyanin, that results in their down-regulation upon entry into
      stationary phase but, (and in contrast to wildtype strains) continued production
      in prolonged stationary phase. These findings may have consequences for chronic
      infection if mucoid P. aeruginosa were to continue to make virulence factors
      under non-growing conditions during infection. These changes resulted in part
      from a severe down-regulation of both AHL-and AQ (PQS)-dependent quorum sensing
      systems. In trans expression of the cAMP-dependent transcription factor Vfr
      restored both quorum sensing defects and virulence factor production in early
      stationary phase. Our findings have implications for understanding the evolution
      of P. aeruginosa during CF lung infection and it demonstrates that mucA22
      mutation provides a second mechanism, in addition to the commonly occurring lasR
      mutations, of down-regulating quorum sensing during chronic infection this may
      provide a selection pressure for the mucoid switch in the CF lung. 

PMID- 24852383
TI  - Copper-catalyzed esterification of alkylbenzenes with cyclic ethers and
      cycloalkanes via C(sp3)-H activation following cross-dehydrogenative coupling.
AB  - A copper-catalyzed cross-dehydrogenative coupling strategy has been developed for
      the synthesis of two classes of esters from simple solvents. The reaction of
      methylarenes with cyclic ethers resulted in alpha-acyloxy ethers involving four
      sp(3) C-H cleavages, while treatment of methylarenes with cycloalkanes led to the
      formation of allyl esters at the expense of six consecutive sp(3) C-H bonds. 

PMID- 24852382
TI  - Plasma omentin levels in drug-free patients with schizophrenia.
AB  - AIMS: We aimed to investigate plasma omentin concentrations in non-obese, drug
      free patients with schizophrenia in comparison with healthy volunteers. METHOD:
      Thirty-two patients with schizophrenia and 33 control subjects were recruited.
      Plasma omentin levels were determined by enzyme-linked immunosorbent assay.
      RESULTS: Plasma levels of omentin (ng/ml) were found to be markedly lower in
      patients with schizophrenia (median = 7.7, 25th percentile = 6.3, 75th percentile
      = 604.9) than in controls (median = 486, 25th percentile = 326, 75th percentile =
      794.2, p < 0.01). No significant difference was found between drug-free (n = 23)
      and drug-naive (n = 9) patients with respect to plasma omentin levels. Omentin
      concentrations correlated negatively with severity of illness, suggesting that
      patients with more severe pathology had lower fasting levels of omentin (n = 32;
      r = -0.387; p = 0.029). CONCLUSION: The present results suggest that plasma
      omentin levels are decreased in physically healthy, non-obese, antipsychotic-free
      patients with schizophrenia when compared with physically and mentally healthy
      individuals. To our knowledge, this is the first study that demonstrated the
      association between omentin and schizophrenia.

PMID- 24852384
TI  - Minimally Invasive Surgery in Patients With Adolescent Idiopathic Scoliosis: Is
      it Better than the Standard Approach? A 2-Year Follow-up Study.
AB  - STUDY DESIGN: This is a retrospective controlled study. OBJECTIVE: To compare the
      safety and efficacy of minimally invasive surgery (MIS) for the surgical
      management of adolescent idiopathic scoliosis (AIS) to the standard open
      posterior approach (PSF). SUMMARY OF BACKGROUND DATA: MIS approaches offer the
      potential to reduce soft-tissue trauma, intraoperative blood loss, and surgical
      site infection. Thus far, MIS has been successfully utilized for the surgical
      correction of multilevel spine pathology in adults. It is not yet known if these
      results can be replicated in the surgical management of AIS. MATERIALS AND
      METHODS: Seven MIS patients were compared with 15 PSF patients using minimum 2
      year follow-up data. Parameters studied included preoperative patient and
      deformity characteristics, perioperative details, extent of deformity correction,
      and complications. Data were compared using Mann-Whitney tests for continuous
      variables and Fisher exact tests for categorical variables. RESULTS: The MIS and
      PSF groups were similar for all preoperative characteristics collected (P>0.05).
      MIS patients had fewer fixation points (P=0.015), but a longer median operative
      time (P=0.011). There was no significant difference in estimated blood loss (EBL)
      (P=0.051), EBL/fixation point (P=0.204), or amount of fluids administered
      (P=0.888). Postoperative recovery did not differ between the 2 groups in number
      of intensive care unit days (P=0.362), length of hospital stay (P=0.472), time to
      mobilization (P=1.00), Visual Analogue Scale pain scores (P=0.698), or patient
      controlled analgesia (P=1.00). The MIS technique had similar deformity
      correction, screw placement accuracy, and fusion status when compared with the
      PSF group. MIS patients had lower blood transfusion rate (P=0.02), shorter fusion
      (P=0.046) and fewer pedicle screws (P=0.015). CONCLUSIONS: The short-term
      advantages seen in MIS for adult scoliosis were not as obvious in our series. We
      found similar deformity correction and adequate fusion, however shortcomings
      related to learning curve, and instrumentation persist. MIS surgery is an
      innovative treatment for AIS that is technically feasible with significantly
      lower transfusion rate, shorter fusion lenghts and lesser pedicle screw fixation.
      Despite these advanatges, its role in AIS is currently difficut to define.

PMID- 24852385
TI  - The late Early Pleistocene human dental remains from Uadi Aalad and Mulhuli-Amo
      (Buia), Eritrean Danakil: macromorphology and microstructure.
AB  - Fieldwork performed during the last 15 years in various Early Pleistocene East
      African sites has significantly enlarged the fossil record of Homo erectus sensu
      lato (s.l.). Additional evidence comes from the Danakil Depression of Eritrea,
      where over 200 late Early to early Middle Pleistocene sites have been identified
      within a ~1000 m-thick sedimentary succession outcropping in the Dandiero Rift
      Basin, near Buia. Along with an adult cranium (UA 31), which displays a blend of
      H. erectus-like and derived morpho-architectural features and three pelvic
      remains, two isolated permanent incisors (UA 222 and UA 369) have also been
      recovered from the 1 Ma (millions of years ago) Homo-bearing outcrop of Uadi
      Aalad. Since 2010, our surveys have expanded to the nearby (4.7 km) site of
      Mulhuli-Amo (MA). This is a fossiliferous area that has been preliminarily
      surveyed because of its exceptional concentration of Acheulean stone tools. So
      far, the site has yielded 10 human remains, including the unworn crown of a lower
      permanent molar (MA 93). Using diverse analytical tools (including high
      resolution MUCT and MUMRI), we analysed the external and internal macromorphology
      and microstructure of the three specimens, and whenever possible compared the
      results with similar evidence from early Homo, H. erectus s.l., H. antecessor, H.
      heidelbergensis (from North Africa), Neanderthals and modern humans. We also
      assessed the UA 369 lower incisor from Uadi Aalad for root completion timing and
      showed that it compares well with data for root apex closure in modern human
      populations. 

PMID- 24852387
TI  - The professional practice of registered nurses.

PMID- 24852386
TI  - Coccygeal movement test: an objective, non-invasive test for localization of the
      pelvic floor muscles in healthy women.
AB  - OBJECTIVE: To evaluate the use of palpation of the coccyx (the coccygeal movement
      test, CMT) as a possible objective screening tool for the assessment of adequate
      localization of the pelvic floor muscles (PFMs). SUBJECTS AND METHODS: Twenty
      four healthy female volunteers, known to be able to locate their PFMs, were given
      instructions (allocated at random) to perform a 'correct contraction',
      'straining' or 'nothing' when examined by six independent assessors using the
      CMT. The assessors were blinded to the instructions and to the test results
      recorded by other assessors. Data were available for 137 observations, and these
      were dichotomized into either 'able to contract' ('correct contraction') or 'not
      able to contract' ('straining' or 'nothing'). This information was used to
      calculate the sensitivity, specificity and positive and negative predictive
      values for the CMT. RESULTS: The CMT correctly identified 56/58 observations when
      women did not perform the contraction of the PFMs compared to 61/79 observations
      when they did. Hence, the sensitivity and specificity were 97 and 77%,
      respectively. CONCLUSION: This study showed that the CMT was a useful test to
      identify women who were able to localize their PFMs compared to those who were
      not, making it a potentially useful initial screening test in structured training
      programmes for the PFMs.

PMID- 24852388
TI  - Ropinirole regulates emotionality and neuronal activity markers in the limbic
      forebrain.
AB  - Restless legs syndrome (RLS) and Parkinson's disease (PD) are movement disorders
      usually accompanied by emotional and cognitive deficits. Although D3/D2 receptor
      agonists are effective against motor and non-motor deficits in RLS and PD, the
      exact behavioral and neurochemical effects of these drugs are not clearly
      defined. This study aimed to evaluate the effects of acute ropinirole (0, 0.1, 1
      or 10 mg/kg, i.p.), a preferential D3/D2 receptor agonist, on intracranial self
      stimulation (ICSS), spontaneous motor activity, anxiety- and depression-like
      behaviors, spatial reference and working memory in rats as well as on certain
      markers of neuronal activity, i.e. induction of immediate early genes, such as c
      fos and arc, and crucial phosphorylations on GluA1 subunit of alpha-Amino-3
      hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and NA1, NA2A and
      NA2B subunits of N-methyl-D-aspartate (NMDA) receptors. Ropinirole decreased ICSS
      thresholds and induced anxiolytic- and antidepressive-like effects without
      affecting motor activity or spatial memory. The effects on emotionality were
      associated with a decrease in p-Ser897-NA1 and an increase in p-Tyr1472-NA2B in
      the ventral striatum as well as an increased induction of c-fos messenger RNA
      (mRNA) in the prefrontal cortex (PFC) and decreased expression of arc mRNA in the
      striatum and the shell of the nucleus accumbens. Our data indicate that
      ropinirole significantly affects emotionality at doses (1-10 mg/kg, i.p.) that
      exert no robust effects on locomotion or cognition. The data reinforce the use of
      D3/D2 receptor agonists in the treatment of RLS and PD patients characterized by
      emotional deficits and suggest that altered NMDA-mediated neurotransmission in
      the limbic forebrain may underlie some of ropinirole's therapeutic actions.

PMID- 24852389
TI  - Funding decisions for newborn screening: a comparative review of 22 decision
      processes in Europe.
AB  - Decision-makers need to make choices to improve public health. Population-based
      newborn screening (NBS) is considered as one strategy to prevent adverse health
      outcomes and address rare disease patients' needs. The aim of this study was to
      describe key characteristics of decisions for funding new NBS programmes in
      Europe. We analysed past decisions using a conceptual framework. It incorporates
      indicators that capture the steps of decision processes by health care payers.
      Based on an internet survey, we compared 22 decisions for which answers among two
      respondents were validated for each observation. The frequencies of indicators
      were calculated to elicit key characteristics. All decisions resulted in
      positive, mostly unrestricted funding. Stakeholder participation was diverse
      focusing on information provision or voting. Often, decisions were not fully
      transparent. Assessment of NBS technologies concentrated on expert opinion,
      literature review and rough cost estimates. Most important appraisal criteria
      were effectiveness (i.e., health gain from testing for the children being
      screened), disease severity and availability of treatments. Some common and
      diverging key characteristics were identified. Although no evidence of explicit
      healthcare rationing was found, processes may be improved in respect of
      transparency and scientific rigour of assessment. 

PMID- 24852390
TI  - Geographical distribution patterns of iodine in drinking-water and its
      associations with geological factors in Shandong Province, China.
AB  - County-based spatial distribution characteristics and the related geological
      factors for iodine in drinking-water were studied in Shandong Province (China).
      Spatial autocorrelation analysis and spatial scan statistic were applied to
      analyze the spatial characteristics. Generalized linear models (GLMs) and
      geographically weighted regression (GWR) studies were conducted to explore the
      relationship between water iodine level and its related geological factors. The
      spatial distribution of iodine in drinking-water was significantly heterogeneous
      in Shandong Province (Moran's I = 0.52, Z = 7.4, p < 0.001). Two clusters for
      high iodine in drinking-water were identified in the south-western and north
      western parts of Shandong Province by the purely spatial scan statistic approach.
      Both GLMs and GWR indicated a significantly global association between iodine in
      drinking-water and geological factors. Furthermore, GWR showed obviously spatial
      variability across the study region. Soil type and distance to Yellow River were
      statistically significant at most areas of Shandong Province, confirming the
      hypothesis that the Yellow River causes iodine deposits in Shandong Province. Our
      results suggested that the more effective regional monitoring plan and water
      improvement strategies should be strengthened targeting at the cluster areas
      based on the characteristics of geological factors and the spatial variability of
      local relationships between iodine in drinking-water and geological factors. 

PMID- 24852391
TI  - Green perspectives for public health: a narrative review on the physiological
      effects of experiencing outdoor nature.
AB  - Natural environments offer a high potential for human well-being, restoration and
      stress recovery in terms of allostatic load. A growing body of literature is
      investigating psychological and physiological health benefits of contact with
      Nature. So far, a synthesis of physiological health outcomes of direct outdoor
      nature experiences and its potential for improving Public Health is missing. We
      were interested in summarizing the outcomes of studies that investigated
      physiological outcomes of experiencing Nature measuring at least one
      physiological parameter during the last two decades. Studies on effects of indoor
      or simulated Nature exposure via videos or photos, animal contact, and wood as
      building material were excluded from further analysis. As an online literature
      research delivered heterogeneous data inappropriate for quantitative synthesis
      approaches, we descriptively summarized and narratively synthesized studies. The
      procedure started with 1,187 titles. Research articles in English language
      published in international peer-reviewed journals that investigated the effects
      of natural outdoor environments on humans by were included. We identified 17
      relevant articles reporting on effects of Nature by measuring 20 different
      physiological parameters. We assigned these parameters to one of the four body
      systems brain activity, cardiovascular system, endocrine system, and immune
      function. These studies reported mainly direct and positive effects, however, our
      analyses revealed heterogeneous outcomes regarding significance of results. Most
      of the studies were conducted in Japan, based on quite small samples,
      predominantly with male students as participants in a cross-sectional design. In
      general, our narrative review provided an ambiguous illustration of the effects
      outdoor nature exerted on physiological parameters. However, the majority of
      studies reported significant positive effects. A harmonizing effect of Nature,
      especially on physiological stress reactions, was found across all body systems.
      From a Public Health perspective, interdisciplinary work on utilizing benefits of
      Nature regarding health promotion, disease prevention, and nature-based therapy
      should be optimized in order to eventually diminish given methodological
      limitations from mono-disciplinary studies. 

PMID- 24852393
TI  - Influence of viticulture practices on grape aroma precursors and their relation
      with wine aroma.
AB  - BACKGROUND: The effects of two different operations in the vineyard (basal leaf
      plucking and head trimming) on the synthesis of aromatic precursors in the grape
      and their impact on wine aroma have been studied and compared with a control
      sample. The study was carried out over two consecutive years with four different
      varieties. Glycosidic precursors were analysed in grapes and volatile compounds
      were studied in the wines. ANOVA studies were performed to study the effect of
      the vintage, variety and treatment for each of the compounds released from their
      precursors. RESULTS: Regarding treatment, the highest values in the concentration
      of free aroma compounds were achieved in the leaf plucking grapes, except for
      Chardonnay. Significant and positive correlations between aromatic precursors of
      terpenes present in grapes and their released form in wines were found for all
      varieties. For norisoprenoids, significant and positive correlations were
      exclusively found for Chardonnay and for phenols and vanillins in the year 2010
      the correlations were high in three of the four varieties studied. CONCLUSION: In
      the assays of the 2 years, more precursors were synthesised in Merlot,
      Gewurztraminer and Tempranillo grapes if the vineyards were plucked.

PMID- 24852392
TI  - Diabetes prevention in the New York City Sikh Asian Indian community: a pilot
      study.
AB  - India has one of the highest burdens of diabetes worldwide, and rates of diabetes
      are also high among Asian Indian immigrants that have migrated into the United
      States (U.S.). Sikhs represent a significant portion of Asian Indians in the U.S.
      Diabetes prevention programs have shown the benefits of using lifestyle
      intervention to reduce diabetes risk, yet there have been no culturally-tailored
      programs for diabetes prevention in the Sikh community. Using a quasi
      experimental two-arm design, 126 Sikh Asian Indians living in New York City were
      enrolled in a six-workshop intervention led by community health workers. A total
      of 108 participants completed baseline and 6-month follow-up surveys between
      March 2012 and October 2013. Main outcome measures included clinical variables
      (weight, body mass index (BMI), waist circumference, blood pressure, glucose, and
      cholesterol) and health behaviors (changes in physical activity, food behaviors,
      and diabetes knowledge). Changes were significant for the treatment group in
      weight, BMI, waist circumference, blood pressure, glucose, physical activity,
      food behaviors, and diabetes knowledge, and between group differences were
      significant for glucose, diabetes knowledge, portion control, and physical
      activity social interaction. Retention rates were high. Findings demonstrate that
      a diabetes prevention program in the Sikh community is acceptable, feasible, and
      efficacious. 

PMID- 24852394
TI  - PL03.05 An intergroup randomized phase III comparison of standard-dose (60 Gy) vs
      high-dose (74 Gy) chemoradiotherapy (CRT) +/- cetuximab (cetux) for stage III non
      small cell lung cancer (NSCLC): results on cetux from RTOG 0617.

PMID- 24852395
TI  - MO06.12 Efficacy and safety of paclitaxel and carboplatin with bevacizumab for
      the first-line treatment of patients with nonsquamous non-small cell lung cancer
      (NSCLC): analyses based on age in the phase 3 PointBreak and E4599 trials.

PMID- 24852396
TI  - O02.03 Value of adding erlotinib to thoracic radiation therapy with chemotherapy
      for stage III non-small cell lung cancer: a prospective phase II study.

PMID- 24852397
TI  - MO06.03 Bevacizumab and erlotinib or bevacizumab, cisplatin and pemetrexed in
      patients with metastatic non-small cell lung cancer: EGFR mutation based
      treatment allocation and repeat biopsy at progression in the SAKK19/09 (BIOPRO)
      trial.

PMID- 24852398
TI  - Clinical Trials of PD-1 and PD-L1 inhibitors in NSCLC.

PMID- 24852399
TI  - Commentary: highlights in NSCLC from the 15th World Conference on Lung Cancer.

PMID- 24852400
TI  - Adaptable healing patient room for stroke patients. A staff evaluation.
AB  - INTRODUCTION: This article is part of the focus theme of Methods of Information
      in Medicine on "Pervasive Intelligent Technologies for Health". BACKGROUND: This
      paper addresses the evaluation with hospital staff of an in-patient environment
      that supports patients, family, nursing staff and medical specialists during the
      recovery process of neurology patients and especially patients recovering from a
      stroke. We describe the methods that were used to evaluate the Adaptive Daily
      Rhythm Atmospheres (ADRA), Artificial Skylight (AS) and Adaptive Stimulus Dosage
      (ASD) concepts. OBJECTIVES: The goal of this evaluation was to gather qualitative
      and quantitative feedback from hospital staff about the usefulness, the usability
      and desirability of the Adaptive Daily Rhythm Atmospheres (ADRA), Artificial
      Skylight (AS) and Adaptive Stimulus Dosage (ASD) concepts that were implemented
      as different phases of a novel healing patient room. This paper reports the
      effects of these concepts with regard to 1) the healing process of the patient
      and 2) the workflow of the staff. These results are part of a larger R&D project
      and provide the initial feedback in an iterative user-centered design
      methodology. METHODS: After signing informed consents, the group of participants
      was taken to the laboratory environment where they were introduced to the
      Adaptive Healing Environment Patient Room and where they could also experience
      the room. Then, the participants were seated next to the patient bed so they had
      a similar viewing angle as the patients. The participants received a booklet with
      questionnaires. The items on this questionnaire addressed the influence on the
      healing process (i.e., the possible effect the concept/phase has on the healing
      process of the patient, meaning faster recovery, better sleep and enhanced well
      being) and influence on the workflow (i.e., the possible effect of such a
      concept/phase on the working activities of the staff in the ward). We presented
      every concept (AS and ASD) and all the phases of ADRA. After every presentation
      of the concept or phase of the ADRA system the participants rated the concept or
      phase anonymously on a 7-point Likert scale. In addition to rating the phase in
      the therefore designed booklets, they were also asked to motivate their ratings
      in writing. Subsequently, a focus group discussion took place. During the
      discussion the two note takers wrote down all the comments. Afterwards the
      quantitative results were analyzed with the non-parametric Kruskal-Wallis test.
      Significant effects were further analyzed in a post-hoc Mann-Whitney test.
      RESULTS: The results show that hospital staff expects a positive effect on the
      healing process of the patient for the Artificial Skylight, the Adaptable
      Stimulus Dosage concept and the different ADRA phases that provide a clear daily
      rhythm structure during the day. In fact the staff members from different
      healthcare institutions and with different professional roles agreed on most
      aspects. In addition, the staff also expected a positive effect for almost all
      phases on the efficiency of the clinical workflow, also for the AS and ASD
      concepts. This is a very promising result as the phases were designed primarily
      with the healing effect of the patient in mind. CONCLUSIONS: The hospital staff
      evaluation in the laboratory setting gave us an indication of the likely impact
      of the Adaptive Healing Environment Patient Room on the healing progress of
      patients. Furthermore, this laboratory evaluation of the concepts was an
      important step that enabled to improve the shortcomings of the current concept
      before starting clinical trials. In addition, we generated feedback from
      different departments from different institutions, which suggest that they all
      see similar added values for the patient room.

PMID- 24852401
TI  - Response-guided therapy in patients with genotype 1 hepatitis C virus: current
      status and future prospects.
AB  - On-treatment responses to antiviral therapy are used to determine duration of
      therapy in patients being treated for genotype 1 hepatitis C virus infection.
      Such use of response-guided therapy has successfully reduced exposure of patients
      to the side-effects of pegylated interferon and ribavirin without jeopardizing
      overall treatment success. Response-guided therapy is an integral part of
      treatment using the current standard treatments involving the direct-acting
      antiviral (DAA) agents--boceprevir or telaprevir--combined with pegylated
      interferon/ribavirin. Improvements in our understanding of the kinetics of viral
      load during antiviral therapy have shown us that more potent suppression of viral
      replication increases the rate of viral eradication, providing impetus for the
      development of more potent DAAs. Emerging results from clinical trials of these
      agents--including trials of interferon-free DAA combinations--suggest that very
      high rates of viral eradication are achievable, even in patients who failed to
      respond to previous courses of interferon-based therapy. Furthermore, because of
      these high rates of treatment success, on-treatment assessment of viral response
      may become unnecessary. The field of hepatitis C virus therapy is evolving
      rapidly and current trends indicate that the era of simple treatment regimens
      with high rates of success and good tolerability are near.

PMID- 24852402
TI  - PEGylated fluorescent carbon nanoparticles for noninvasive heart imaging.
AB  - Fluorescent carbon nanoparticles (CNP) have gained much attention due to their
      unique fluorescent properties and safety. In this study, we evaluated the
      potential application of CNP and PEGylated CNP (PEG-CNP) in noninvasive heart
      imaging. CNP was prepared by hydrothermal treatment of silk. The particle size
      and zeta potential of CNP were 121.8 nm and -3.7 mV, respectively, which did not
      change significantly after PEGylation with a PEG density of 4.43 +/- 0.02 MUg/mg
      CNP. FTIR and XPS showed that CNP possessed several functional groups, such as 
      COOH, -OH, and NH2, which could be utilized for PEGylation and other
      modifications. CNP displayed strong blue fluorescence after excitation at the
      wavelength of 375 nm. PEG-CNP displayed better serum stability compared to CNP.
      The hemolysis rate of PEG-CNP was lower than that of CNP, suggesting PEGylation
      could enhance the hemocompatibility of CNP. Both CNP and PEG-CNP showed higher
      uptake capacity by H9c2 cells (a heart cell line) than that by human umbilical
      vein endothelial cells (HUVEC), suggesting the particles tend to be selectively
      taken up by heart cells. Both CNP and PEG-CNP were proven to be taken up through
      endosome-mediated pathway, and the colocalization of nanoparticles with
      mitochondria was also observed. In vivo results demonstrated that CNP could
      target heart with much higher fluorescent intensity than liver and spleen.
      Although PEGylation could decrease the distribution in heart, it remained high
      for PEG-CNP. In conclusion, CNP could be used for heart imaging, and moreover,
      PEGylation could improve the stability and biocompatibility of CNP. 

PMID- 24852404
TI  - Probing the impact of sex steroids and menopause-related sex steroid deprivation
      on modulation of immune senescence.
AB  - Immune senescence denotes the general decline in immune system function,
      characterized by a reduced immune response and an increased inflammatory state.
      Menopause is a natural change in a women's life, the menopause-related low
      estrogen levels affecting many body functions, among them the immune system.
      Numerous human studies with menopausal women and animal models with surgically
      induced menopause show a clear impact of sex steroids in immune responses. Female
      superiority in vaccination response and predisposition to infections are
      eliminated after menopause, while during menopause inflammatory cytokines such as
      Tumor Necrosis Factor-alpha (TNF-alpha), Interleukins-1beta, 6, 8 and 13 (IL
      1beta, IL-6, IL-8, IL-13) and Monocyte Chemoattractant Protein-1 (MCP-1) are
      increased, implying a molecular connection of sex steroid loss with immune
      senescence. Moreover, immune cells modify their number and function after the
      menopausal transition, this offering another explanation for immune senescence.
      Until now most of the existing studies have concluded that menopause plays an
      additional role to aging in immune senescence. While it is clear that we are as
      yet far from thoroughly understanding the molecular pathways connecting sex
      steroids and menopause with immune senescence, such knowledge is highly likely to
      enable future targeted interventions in treatment and prevention of age-related
      diseases in women. 

PMID- 24852405
TI  - Primary endovascular treatment of post-irradiated carotid pseudoaneurysm at the
      skull base with the Pipeline embolization device.
AB  - BACKGROUND: A post-irradiated carotid pseudoaneurysm at the skull base can cause
      life-threatening blowout syndrome. Conventional treatments include parent vessel
      occlusion, endovascular coiling or covered stenting. Use of the Pipeline
      embolization device (PED) for pseudoaneurysm exclusion at the skull base is not
      well described. OBJECTIVE: To report the clinical and angiographic outcome after
      using multiple PEDs to treat recently ruptured radiation-induced carotid
      pseudoaneurysms at the skull base. METHODS: Retrospective review of the clinical
      and angiographic records of patients who received PEDs as primary treatment for
      skull base carotid pseudoaneurysm between April 1, 2011 to March 31, 2013.
      RESULTS: Seven patients (five men, two women) with a mean age of 58 years (range
      47-65) were treated in the study period. Primary treatment with the PED alone,
      with adjunct coil embolization in two patients, achieved immediate hemostasis in
      all patients, with no pseudoaneurysm rebleeding after a mean follow-up of 15.3
      months (range 4-24 months). One patient had periprocedural cerebral infarction.
      Delayed internal carotid artery occlusion secondary to in-stent thrombosis
      occurred in three patients, one of whom had lacunar infarct and two remained
      asymptomatic. CONCLUSIONS: Endovascular treatment with the PED was effective in
      excluding skull base post-irradiated carotid pseudoaneurysms and preventing
      recurrent blowout. However, the risk of ischemic complications in this group of
      patients was high and our experience did not support the use of flow diverters as
      a first-line treatment for this condition.

PMID- 24852403
TI  - Treatment of climacteric symptoms in breast cancer patients: a retrospective
      study from a medication databank.
AB  - INTRODUCTION: Women affected by breast cancer (BC) will often go through
      menopause at an earlier age and display more frequent and severe symptoms than
      women who have a natural menopause. The safety of hormone replacement therapy
      (HRT) and vaginal estrogens for BC survivors has been debated over time and
      remains unclear. Non hormonal therapies such as antidepressants, gabapentine and
      clonidine may be useful for those patients but there are few data about their
      safety. AIM: This retrospective study analyses the use by BC patients of
      treatments known to alleviate climacteric symptoms. MATERIAL AND METHOD: Post
      menopausal Estrogen Receptors positive (ER+) BC patients, aged 45-69, were
      identified as having bought, at least once, an aromatase inhibitor (AI) or
      tamoxifen between the years 2000 and 2012 through a pharmaceutical databank in
      Belgium. Among them, we defined users of a climacteric treatment those who
      bought, at least once, HRT, vaginal topical estrogens, antidepressants, clonidine
      and gabapentine. RESULTS: We identified 2530 BC patients. Among them, 45% were
      buying a treatment known to alleviate menopausal symptoms. The majority of these
      treatments were non-HRT therapies. HRT and vaginal estrogens were seldom bought
      (respectively 1.1% and 6%), but 3% bought vaginal estrogens while buying AI.
      About 9.2% of tamoxifen users patients bought antidepressants implicated in
      tamoxifen metabolism at the same time as tamoxifen. CONCLUSIONS: Most BC patients
      follow current guidelines contra-indicating the use of HRT after BC, they use non
      hormonal therapies. In some cases they use unfortunately antidepressants that may
      alter the metabolism of tamoxifen.

PMID- 24852406
TI  - Robust post-stall perching with a simple fixed-wing glider using LQR-Trees.
AB  - Birds routinely execute post-stall maneuvers with a speed and precision far
      beyond the capabilities of our best aircraft control systems. One remarkable
      example is a bird exploiting post-stall pressure drag in order to rapidly
      decelerate to land on a perch. Stall is typically associated with a loss of
      control authority, and it is tempting to attribute this agility of birds to the
      intricate morphology of the wings and tail, to their precision sensing apparatus,
      or their ability to perform thrust vectoring. Here we ask whether an extremely
      simple fixed-wing glider (no propeller) with only a single actuator in the tail
      is capable of landing precisely on a perch from a large range of initial
      conditions. To answer this question, we focus on the design of the flight control
      system; building upon previous work which used linear feedback control design
      based on quadratic regulators (LQR), we develop nonlinear feedback control based
      on nonlinear model-predictive control and 'LQR-Trees'. Through simulation using a
      flat-plate model of the glider, we find that both nonlinear methods are capable
      of achieving an accurate bird-like perching maneuver from a large range of
      initial conditions; the 'LQR-Trees' algorithm is particularly useful due to its
      low computational burden at runtime and its inherent performance guarantees. With
      this in mind, we then implement the 'LQR-Trees' algorithm on real hardware and
      demonstrate a 95 percent perching success rate over 147 flights for a wide range
      of initial speeds. These results suggest that, at least in the absence of
      significant disturbances like wind gusts, complex wing morphology and sensing are
      not strictly required to achieve accurate and robust perching even in the post
      stall flow regime. 

PMID- 24852407
TI  - Squamous cell carcinoma with clear-cell features of the palpebral conjunctiva.

PMID- 24852408
TI  - Distribution, source, fate and bioaccumulation of methyl siloxanes in marine
      environment.
AB  - Studies have shown that some cyclic methyl siloxanes were identified as
      characterized of persistent, bioaccumulated, toxic, and potential to ecological
      harm. In this study, we determined methyl siloxanes in seawater, sediment and
      bottom fish samples collected from marine environment in Northeast China. The
      mean concentrations of total methyl siloxanes were 46.1 +/- 27.2 ng/L, 12.4 +/-
      5.39 ng/g dry weight (dw) and 5.10 +/- 1.34 wet weight (ww) in seawater, sediment
      and fish, respectively. Very strong and significant correlations (r = 0.94, p <
      0.0001) were found in compositions of methyl siloxanes between seawater and
      sewage, indicating that sewage was the main source of methyl siloxanes in the
      marine area studied. It was found that the mean value of biota-sediment
      accumulation factor (BSAF) was.0.716 +/- 0.456 for D4, 0.103 +/- 0.0771 for D5,
      1.06 +/- 0.528 for D6 and 0.877 +/- 0.530 for D7. 

PMID- 24852409
TI  - Is there a relationship between earthworm energy reserves and metal availability
      after exposure to field-contaminated soils?
AB  - Generic biomarkers are needed to assess environmental risks in metal polluted
      soils. We assessed the strength of the relationship between earthworm energy
      reserves and metal availability under conditions of cocktail of metals at low
      doses and large range of soil parameters. Aporrectodea caliginosa was exposed in
      laboratory to a panel of soils differing in Cd, Pb and Zn total and available
      (CaCl2 and EDTA-extractable) concentrations, and in soil texture, pH, CEC and
      organic-C. Glycogen, protein and lipid contents were recorded in exposed worms.
      Glycogen contents were not linked to the explaining variables considered.
      Variable selection identified CaCl2 extractable metals concentrations and soil
      texture as the main factors affecting protein and lipid contents. The results
      showed opposite effects of Pb and Zn, high inter-individual variability of
      biomarkers and weak relationships with easily extractable metals. Our results
      support the lack of genericity of energy reserves in earthworms exposed to field
      contaminated soils. 

PMID- 24852410
TI  - The fate of per- and polyfluoroalkyl substances within a melting snowpack of a
      boreal forest.
AB  - Per- and polyfluoroalkyl substances (PFAS) were measured systematically in a
      snowpack in northern Sweden to determine chemical behaviour during seasonal melt.
      Average PFAS concentrations were generally low, but displayed a wide range with
      median (range) concentrations of PFOA and PFOS of 66.5 pg L(-1) (ND-122) and 20.5
      pg L(-1) (2.60-253) respectively. Average concentrations of the shorter chain, C4
      and C5 perfluoroalkyl carboxylates (PFCAs) and perfluoroalkyl sulfonates (PFSAs),
      were ~10-fold higher. Differences in the PFAS concentrations and profile were
      observed between surface snow and deeper layers, with evidence of PFAS migration
      to deeper snow layers as melt progressed. Chemical loads (ng m(-2)) for C4-9
      PFCAs decreased gradually as melt progressed, but increased for C4, C6-8 PFSAs
      and the longer chain C10-12 PFCAs. This enrichment in the diminishing snowpack is
      an unusual phenomenon that will affect PFAS elution with meltwater and subsequent
      entry to catchment surface waters. 

PMID- 24852411
TI  - Investigating the life-cycle and growth rate of Pediastrum boryanum and the
      implications for wastewater treatment high rate algal ponds.
AB  - The colonial alga Pediastrum boryanum has beneficial characteristics for
      wastewater treatment High Rate Algal Ponds (HRAP) including high biomass
      productivity and settleability. Our previous work has shown that these
      characteristics are enhanced when a portion of gravity harvested algae is
      recycled back to the pond. To help understand the mechanisms behind the improved
      performance of P. boryanum dominated HRAP with algal recycling, this study
      investigated the life-cycle of P. boryanum. Experiments determined the exact
      timing and growth rate of P. boryanum life-cycle stages ('juvenile', 'growth' and
      'reproductive') under four combinations of light and temperature (250 or 120
      MUMol/m(2)/s; 20 or 10  degrees C). Single juvenile 16-celled colonies were grown
      in microcosms on an inverted microscope and photographed every 15 min until
      reproduction ceased. Two asexual life-cycles and a rarely occurring sexual life
      cycle were observed. The time required to achieve asexual reproductive maturity
      increased from 52 h (high light and temperature) to 307 h (low light and
      temperature), indicating that the minimum hydraulic retention time or mean cell
      residence time (MCRT) must be higher than these values to sustain a P. boryanum
      HRAP culture under ambient conditions. The net growth rate of a P. boryanum
      colony varied between life-cycle stages (growth > juvenile > reproductive). This
      suggests that the higher biomass productivity measured in HRAP with algal
      recycling could be due to both the increased MCRT and an increase in the net
      growth rate of the HRAP culture by 'seeding' with faster growing colonies. 

PMID- 24852412
TI  - New systematic methodology for incorporating dynamic heat transfer modelling in
      multi-phase biochemical reactors.
AB  - This paper presents a new modelling methodology for dynamically predicting the
      heat produced or consumed in the transformations of any biological reactor using
      Hess's law. Starting from a complete description of model components
      stoichiometry and formation enthalpies, the proposed modelling methodology has
      integrated successfully the simultaneous calculation of both the conventional
      mass balances and the enthalpy change of reaction in an expandable multi-phase
      matrix structure, which facilitates a detailed prediction of the main heat fluxes
      in the biochemical reactors. The methodology has been implemented in a plant-wide
      modelling methodology in order to facilitate the dynamic description of mass and
      heat throughout the plant. After validation with literature data, as illustrative
      examples of the capability of the methodology, two case studies have been
      described. In the first one, a predenitrification-nitrification dynamic process
      has been analysed, with the aim of demonstrating the easy integration of the
      methodology in any system. In the second case study, the simulation of a thermal
      model for an ATAD has shown the potential of the proposed methodology for
      analysing the effect of ventilation and influent characterization. 

PMID- 24852413
TI  - Analysis of bacterial communities and bacterial pathogens in a biogas plant by
      the combination of ethidium monoazide, PCR and Ion Torrent sequencing.
AB  - The present study investigated the changes of bacterial community composition
      including bacterial pathogens along a biogas plant, i.e. from the influent, to
      the biogas reactor and to the post-digester. The effects of post-digestion
      temperature and time on the changes of bacterial community composition and
      bacterial pathogens were also studied. Microbial analysis was made by Ion Torrent
      sequencing of the PCR amplicons from ethidium monoazide treated samples, and
      ethidium monoazide was used to cleave DNA from dead cells and exclude it from PCR
      amplification. Both similarity and taxonomic analysis showed that the bacterial
      community composition in the influent was changed after anaerobic digestion.
      Firmicutes were dominant in all the samples, while Proteobacteria decreased in
      the biogas reactor compared with the influent. Variations of bacterial community
      composition in the biogas reactor with time were also observed. This could be
      attributed to varying composition of the influent. Batch experiments showed that
      the methane recovery from the digested residues (obtained from biogas reactor)
      was mainly related with post-digestion temperature. However, post-digestion time
      rather than temperature had a significant effect on the changes of bacterial
      community composition. The changes of bacterial community composition were also
      reflected in the changes of relative abundance of bacterial pathogens. The
      richness and relative abundance of bacterial pathogens were reduced after
      anaerobic digestion in the biogas reactor. It was found in batch experiments that
      bacterial pathogens showed the highest relative abundance and richness after 30
      days' post-digestion. Streptococcus bovis was found in all the samples. Our
      results showed that special attention should be paid to the post-digestion since
      the increase in relative abundance of bacterial pathogens after post-digestion
      might reflect regrowth of bacterial pathogens and limit biosolids disposal
      vectors. 

PMID- 24852414
TI  - Colloidal synthesis and photocatalytic properties of orthorhombic AgGaS2
      nanocrystals.
AB  - AgGaS2 (AGS) nanocrystals that exist in the orthorhombic phase were successfully
      prepared for the first time through a one-pot colloidal synthetic strategy using
      suitable coordinating solvents. These orthorhombic AGS nanocrystals were found to
      display great potential in visible-light-driven photocatalysis. 

PMID- 24852415
TI  - Advances in the production and handling of encoded microparticles.
AB  - Here we highlight emerging technologies in the synthesis, handling, and
      application of encoded microparticles for multiplexed assays. Traditionally, in
      drug discovery and life sciences research, multiple reactions will be conducted
      in parallel using microwell plate formats or microfluidic implementations, in
      which volumes are confined and reactions annotated by knowledge of what reagents
      were added to each volume. Microparticle-based information carriers provide an
      alternative approach to performing such multiplexed reactions, in which reactions
      and events are instead annotated with unique codes associated with the solid
      phase particle. One challenge has been in creating a unique and large enough code
      set that is also easily readout, and we highlight two approaches that have
      brought orthogonal optical tagging techniques to bear. Another challenge has been
      that in such approaches, reactions have usually been confined to the surface of,
      or within the bulk of the specifically-tagged particle. We also highlight a
      creative approach and strategy for multiplexing - called "partipetting"- in which
      the coded particle can be a carrier of a unique fluid reagent. 

PMID- 24852416
TI  - Transition from pediatric to adult care. eight years after the transition from
      pediatric to adult diabetes care: metabolic control, complications and associated
      diseases.
AB  - BACKGROUND: Transition from pediatric to adult care is a critical process in the
      life of patients with diabetes. AIM: Primary aim of the study was to compare the
      metabolic control between pediatric care and adult care at least 5 years in a
      group of patients with type 1 diabetes mellitus (T1DM). Secondary aim was to
      evaluate the presence of complications, associated diseases and psychological
      psychiatric disorders. SUBJECTS AND METHODS: We obtained data from 73 % (69/94)
      patients (current mean age 34 years) transferred to local adult centers between
      1985 and 2005 at a mean age of 23.8 years. Data were collected for HbA1c,
      diabetic complications and associated diseases. RESULTS: Mean HbA1c did not
      change during the pediatric, transition and adult period [8.4 +/- 1.8 % (68 +/-
      18 mmol/mol), 8.3 +/- 1.4 % (67 +/- 15 mmol/mol) and 8.4 +/- 1.3 % (68 +/- 14
      mmol/mol), respectively]. 13 patients dropped out, after 2-12 years since
      transition, and their HbA1c mean value at transition was 10.4 %. After a mean of
      25.9 years of disease, 35/69 patients (50.7 %) showed retinopathy, and 12/69
      patients (17.3 %) nephropathy. Thyroid diseases were the most frequent associated
      diseases (18.3 %), followed by depression (11.2 %) and benign neoplasms (9.8 %).
      Drug or alcohol addictions were present in four cases (5.6 %). CONCLUSIONS: After
      a mean follow-up of 8 years metabolic control after transition did not change
      significantly in patients constantly attending to adult care centre. Patients
      with diabetes onset between 20 and 40 years ago were free from complications in
      50 % of cases when considering retinopathy and in more than 80 % considering
      nephropathy. Thyroid problems were the most common associated diseases. Poor
      metabolic control at transition is associated with higher risk of drop-out and
      psychosocial morbidity.

PMID- 24852418
TI  - Successful treatment of lung cancer by multimodal endobronchial interventions.
AB  - The innovation of thoracic interventions, such as endobronchial ultrasound and
      photodynamic ablation, has changed the interventional management of lung cancer.
      In this case report, we discuss the case of a successful treatment of
      endobronchial squamous cell carcinoma occluding the left upper lobe bronchus by a
      minimally invasive transbronchial approach. This case was initially planned for a
      sleeve left upper lobectomy. The careful assessment of radiological and
      ultrasonographic imaging concluded that the tumor was early-stage lung cancer.
      Multimodal endobronchial treatment cured the lung cancer without a thoracotomy.
      Pulmonary function was well preserved and no recurrence was found for more than 5
      years. Even in the presence of a bulky endobronchial tumor, if there is no clear
      evidence of extraluminal invasion by computed tomography scan, a local
      bronchoscopic staging of the disease is mandatory.

PMID- 24852417
TI  - Effects of cocaine on the hypothalamic-pituitary-adrenal axis.
AB  - INTRODUCTION: Cocaine hydrochloride is a psychoactive substance extracted from
      the leaves of plants called Erythroxylum coca. Cocaine is the second most
      commonly used drug in the world after cannabis; 20 % of cocaine users will become
      long-term cocaine-dependent patients. Different routes of administration may be
      recognized: smokable modality, intranasal and intravenous. Cocaine is a potent
      stimulant of the sympathetic nervous system and causes structural changes on the
      brain, heart, lung, liver and kidney. It has long been known that use of cocaine
      may produce alterations to the endocrine system. Research on behavioral and
      neuroendocrine effects of cocaine dates back several years ago and has
      increasingly focused on alterations of the hypothalamic-pituitary-adrenal (HPA)
      axis, which appears to be the chief target of cocaine effects. STUDIES: Animal
      (mainly rats and monkeys) and human studies have clearly shown a close relation
      between cocaine consumption and overdrive of the HPA axis. Such activation is
      likely involved, though via a still undefined mechanism, in the behavioral and
      cardiovascular changes of drug abusers as well as in the reinforcement/relapse
      phenomena. Further studies of the pathophysiology of cocaine addicts will help to
      devise new therapeutic strategies for these patients.

PMID- 24852420
TI  - Diagnostic accuracy of cone beam computed tomography compared with intraoral
      radiography for the detection of noncavitated occlusal carious lesions.
AB  - The aim of this study was to evaluate the accuracy of cone beam computed
      tomography (CBCT) in the detection of noncavitated occlusal caries lesions and to
      compare this accuracy with that observed with conventional radiographs. 135 human
      teeth, 67 premolars and 68 molars with macroscopically intact occlusal surfaces,
      were examined by two independent observers using the CBCT system: NewTom 3G
      (Quantitative Radiology) and intraoral conventional film (Kodak Insight). The
      true lesion diagnosis was established by histological examination. The detection
      methods were compared by means of sensitivity, specificity, predictive values and
      accuracy. To assess intra- and interobserver agreement, weighted kappa
      coefficients were computed. Analyses were performed separately for caries
      reaching into dentin and for all noncavitated lesions. For the detection of
      occlusal lesions extending into dentin, sensitivity values were lower for film
      (0.45) when compared with CBCT (0.51), but the differences were not statistically
      significant (p > 0.19). For all occlusal lesions sensitivity values were 0.32 and
      0.22, respectively, for CBCT and film. The specificity scores were high for both
      modalities. Interobserver agreement amounted to 0.93 for the CBCT system and to
      0.87 for film. It was concluded that the use of the 9-inch field of view NewTom
      CBCT unit for the diagnosis of noncavitated occlusal caries cannot be
      recommended.

PMID- 24852419
TI  - Should the subventricular zone be part of the "rad" zone?

PMID- 24852421
TI  - The 3'-terminal 55 nucleotides of bovine coronavirus defective interfering RNA
      harbor cis-acting elements required for both negative- and positive-strand RNA
      synthesis.
AB  - The synthesis of the negative-strand [(-)-strand] complement of the ~30 kilobase,
      positive-strand [(+)-strand] coronaviral genome is a necessary early step for
      genome replication. The identification of cis-acting elements required for (-)
      strand RNA synthesis in coronaviruses, however, has been hampered due to
      insufficiencies in the techniques used to detect the (-)-strand RNA species.
      Here, we employed a method of head-to-tail ligation and real-time quantitative
      reverse transcription polymerase chain reaction (qRT-PCR) to detect and
      quantitate the synthesis of bovine coronavirus (BCoV) defective interfering (DI)
      RNA (-) strands. Furthermore, using the aforementioned techniques along with
      Northern blot assay, we specifically defined the cis-acting RNA elements within
      the 3'-terminal 55 nucleotides (nts) which function in the synthesis of (-)- or
      (+)-strand BCoV DI RNA. The major findings are as follows: (i) nts from -5 to -39
      within the 3'-terminal 55 nts are the cis-acting elements responsible for (-)
      strand BCoV DI RNA synthesis, (ii) nts from -3 to -34 within the 3'-terminal 55
      nts are cis-acting elements required for (+)-strand BCoV DI RNA synthesis, and
      (iii) the nucleotide species at the 3'-most position (-1) is important, but not
      critical, for both (-)- and (+)-strand BCoV DI RNA synthesis. These results
      demonstrate that the 3'-terminal 55 nts in BCoV DI RNA harbor cis-acting RNA
      elements required for both (-)- and (+)-strand DI RNA synthesis and extend our
      knowledge on the mechanisms of coronavirus replication. The method of head-to
      tail ligation and qRT-PCR employed in the study may also be applied to identify
      other cis-acting elements required for (-)-strand RNA synthesis in coronaviruses.

PMID- 24852422
TI  - Pandemic influenza plans in residential care facilities.
AB  - OBJECTIVES: To identify characteristics of residential care facilities (RCFs)
      associated with having a pandemic influenza plan. DESIGN: Nationally
      representative, cross-sectional survey. SETTING: RCFs in the United States.
      PARTICIPANTS: Participating facilities in the 2010 National Survey of RCFs (N =
      2,294), representing 31,030 assisted living facilities and personal care homes.
      MEASUREMENTS: Facility-level characteristics associated with a pandemic influenza
      plan, including general organization descriptors, staffing, resident services,
      and immunization practices. RESULTS: Forty-five percent (95% confidence interval
      (CI) = 43-47%) had a pandemic plan, 14% (95% CI = 13-16%) had a plan in
      preparation, and 41% (95% CI = 38-43%) had no plan. In the multivariable model,
      organization characteristics, staffing, and immunization practices were
      independently associated with the presence of a pandemic preparedness plan.
      Organization characteristics were larger size (extra large, OR = 3.27, 95% CI =
      1.96-5.46; large, OR = 2.60, 95% CI = 1.81-3.75; medium, OR = 1.66, 95% CI = 1.21
      2.27 vs small), not-for-profit status (OR = 1.65, 95% CI = 1.31-2.09 vs for
      profit), and chain affiliation (OR = 1.65, 95% CI = 1.31-2.09 vs nonaffiliated).
      Staffing characteristics included number of registered nurse hours (<15 minutes,
      OR = 1.36, 95% CI = 1.07-1.74 vs no hours), any licensed practical nurse hours
      (OR = 1.47, 95% CI = 1.08-1.99 vs no hours), and at least 75 hours of required
      training for aides (OR = 1.34, 95% CI = 1.05-1.71 vs <75 hours). RCFs with high
      staff influenza vaccination rates (81-100%, OR = 2.12, 95% CI = 1.27-3.53 vs 0%
      vaccinated) were also more likely to have a pandemic plan. CONCLUSION: A majority
      of RCFs lacked a pandemic influenza plan. These facilities were smaller, for
      profit, non-chain-affiliated RCFs and had lower staff vaccination rates. These
      characteristics may help target facilities that need to develop plans to handle a
      pandemic, or other disasters.

PMID- 24852424
TI  - A nasally applied cellulose powder in seasonal allergic rhinitis in adults with
      grass pollen allergy: a double-blind, randomized, placebo-controlled, parallel
      group study.
AB  - BACKGROUND: A nasally applied cellulose powder is increasingly used in many
      countries as a remedy for allergic rhinitis. In 2009, a 4-week study in birch
      pollen-allergic children showed a reduction in nasal symptoms. The best effect
      occurred on days with lower pollen counts. The present study in grass pollen
      allergic adults used the same basic design. METHODS: In May 2013, a double-blind,
      placebo-controlled study was conducted in 108 patients with allergic rhinitis due
      to grass pollen (18-40 years of age). SMS on mobile phones were used as reminders
      of treatment and reporting of symptom scores. RESULTS: We found significant
      reductions in severity scores for sneezing, runny nose, stuffy nose and symptoms
      from eyes and lower airways, both separately and together (all p < 0.001).
      Reflective opinion of effect and guess on treatment at follow-up visits (both p <
      0.001) confirmed a high efficacy. No clinically significant adverse effects were
      reported. CONCLUSIONS: The product provided significant protection against all
      seasonal allergic rhinitis symptoms from both upper and lower airways during the
      grass pollen season in an adult population. The magnitude and scope of efficacy
      support the use of the product as an early choice in the treatment of allergic
      rhinitis.

PMID- 24852423
TI  - Genetic deletion of Mst1 alters T cell function and protects against
      autoimmunity.
AB  - Mammalian sterile 20-like kinase 1 (Mst1) is a MAPK kinase kinase kinase which is
      involved in a wide range of cellular responses, including apoptosis, lymphocyte
      adhesion and trafficking. The contribution of Mst1 to Ag-specific immune
      responses and autoimmunity has not been well defined. In this study, we provide
      evidence for the essential role of Mst1 in T cell differentiation and
      autoimmunity, using both genetic and pharmacologic approaches. Absence of Mst1 in
      mice reduced T cell proliferation and IL-2 production in vitro, blocked cell
      cycle progression, and elevated activation-induced cell death in Th1 cells. Mst1
      deficiency led to a CD4+ T cell development path that was biased toward Th2 and
      immunoregulatory cytokine production with suppressed Th1 responses. In addition,
      Mst1-/- B cells showed decreased stimulation to B cell mitogens in vitro and
      deficient Ag-specific Ig production in vivo. Consistent with altered lymphocyte
      function, deletion of Mst1 reduced the severity of experimental autoimmune
      encephalomyelitis (EAE) and protected against collagen-induced arthritis
      development. Mst1-/- CD4+ T cells displayed an intrinsic defect in their ability
      to respond to encephalitogenic antigens and deletion of Mst1 in the CD4+ T cell
      compartment was sufficient to alleviate CNS inflammation during EAE. These
      findings have prompted the discovery of novel compounds that are potent
      inhibitors of Mst1 and exhibit desirable pharmacokinetic properties. In
      conclusion, this report implicates Mst1 as a critical regulator of adaptive
      immune responses, Th1/Th2-dependent cytokine production, and as a potential
      therapeutic target for immune disorders. 

PMID- 24852425
TI  - Comment on Xu XW et al.: Prognostic significance of VEGF expression in
      osteosarcoma: a meta-analysis.

PMID- 24852426
TI  - Evaluation of urinary XIAP as a diagnostic biomarker of carcinoma of urinary
      bladder.
AB  - Early diagnosis of carcinoma of the bladder remains a challenge. Urine cytology,
      as an adjunct to cystoscopy, is less sensitive for low-grade tumors. X-linked
      inhibitor of apoptosis (XIAP), a negative regulator of apoptotic stimuli and a
      member of apoptosis family, is frequently activated in bladder carcinoma. Our aim
      is to investigate the significance of urinary XIAP for the noninvasive diagnosis
      of transitional cell carcinoma (TCC) of the urinary bladder. We examined urinary
      XIAP expression in a bladder cancer cell line (T24) and in urine of 28 healthy
      individuals, 46 patients of nonmalignant disorders, and 117 cases (69 primary and
      48 recurrent cases) of histologically proven TCC prior to transurethral
      resection, by using real-time PCR, and compared it with voided urinary cytology
      (VUC). XIAP expression was found in T24 cell line and also was found to be
      significantly higher in the cancer group as compared to the controls (p < 0.001).
      XIAP messenger RNA (mRNA) expression showed a significant (p < 0.05) association
      with stage and grade (p < 0.05). XIAP shows the sensitivity of 82.91 % and
      specificity of 78.38 % (p < 0.001), whereas urine cytology had sensitivity of
      66.67 % and specificity of 95.95 % for TCC cases. The combination of XIAP and VUC
      had better sensitivity (98.2 %) and specificity (92.6 %) than they showed
      individually (p < 0.001). XIAP mRNA expression did not significantly correlated
      with the patient's age, sex, and smoking (p > 0.05). Urinary XIAP can be used as
      a noninvasive diagnostic biomarker for bladder TCC in adjunct to cytology mainly
      for low-grade non-muscle-invasive tumors.

PMID- 24852427
TI  - Survivin and HLA-I expression predicts survival of patients with clear cell renal
      cell carcinoma.
AB  - Altered expression of survivin and leukocyte antigen class I (HLA-I) proteins is
      associated with tumor progression. This study investigated their expressions in
      clear cell renal cell carcinoma (ccRCC) tissues for association with a clinical
      significance of ccRCC patients. Ninety ccRCC and 20 normal tissue samples (i.e.,
      control) were immunohistochemically stained for survivin and HLA-I expression for
      an association with clinicopathological data and survival of ccRCC patients.
      Survivin protein was expressed in 82.2 % (74/90) of ccRCC tissue samples compared
      to 0 % in the normal tissues, and HLA-I protein was expressed in 90 % (18/20) of
      the normal tissues vs. 67.8 % (61/90) in ccRCC samples. Survivin expression was
      associated with tumor grade, stage, and lymph node metastasis (p = 0.000, p =
      0.016, and p = 0.001, respectively). Conversely, lost HLA-I expression did not
      have any associations with clinicopathological data (p > 0.05). Survivin-negative
      patients had a higher tumor-free survival rate than patients with survivin
      expression (p = 0.037). Patients with normal HLA-I levels had a higher tumor-free
      survival rate than those with reduced HLA-I levels (p = 0.02). The uni- and
      multivariate analyses indicated that expression of survivin and HLA-I,
      individually and in combination, was an independent predictor for survival of
      ccRCC patients. Overexpression of survivin but reduced HLA-I expression is useful
      in the prediction of tumor-free survival of ccRCC patients.

PMID- 24852428
TI  - Interactive effect of glutathione S-transferase M1 and T1 polymorphisms on
      hepatocellular carcinoma.
AB  - Glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) have been involved in the
      risk of hepatocellular carcinoma (HCC). However, the interactive effect of GSTM1
      and GSTT1 has not been reported previously. The aim of this work was to
      investigate the interaction and synergism of their variants. We identified nine
      publications including 1,085 cases and 2,396 controls containing both GSTM1 and
      GSTT1, and the bi-factor variance analysis of equal repeated test, binary class
      logistic regression analysis, meta-analysis and probability method were used in
      this analysis. Data showed there was no interaction between GSTM1 and GSTT1 null
      genotype variation in HCC development. In addition, individuals with at least one
      null genotype of GSTM1 and GSTT1 had higher susceptibility to HCC (OR = 2.99, 95
      % CI 2.21-4.02). In the control group, the probability of individuals with at
      least one null genotype of GSTM1 and GSTT1 was 0.6624, while in the case group,
      the probability to develop HCC with at least one null genotype of GSTM1 and GSTT1
      increased to 0.1760, which was considered as the changing characteristics of HCC
      occurrence in Chinese population. Our result suggests that there would be no
      direct interaction of GSTM1 and GSTT1 genotype in HCC risk. We speculate that
      GSTM1 and GSTT1 genotype variations have their own independent function in HCC
      development and may mutate independently to cause HCC. The synergism variants of
      the two genes in HCC development have bigger risk in Chinese population.

PMID- 24852429
TI  - The ATP7B genetic polymorphisms predict clinical outcome to platinum-based
      chemotherapy in lung cancer patients.
AB  - This study aims to investigate the influence of ATP7B genetic polymorphism to
      platinum-based chemotherapy in Chinese Han lung cancer patients. A total of 338
      Chinese Han lung cancer patients were enrolled in this study. All patients
      underwent at least two cycles of platinum-based chemotherapy. Four tag SNPs of
      ATP7B (rs1061472, rs9535826, rs7999812, and rs9535828) were selected to evaluate
      their impacts to platinum-based chemotherapy in these patients. ATP7B rs9535828
      and rs9535826 were found to be associated with platinum resistance in Chinese Han
      lung cancer patients. Patients with A allele in ATP7B rs9535828 presented an
      increased susceptibility to platinum drugs (OR 1.96, 95 % CI 1.17-3.30, p <
      0.01). Patients with G allele in ATP7B rs9535826 had the highest susceptibility
      to platinum drugs (OR 2.05, 95 % CI 1.19-3.52, p < 0.01). Our findings suggest
      that ATP7B genetic polymorphisms could affect the therapeutic efficacy of
      platinum-based chemotherapy, and ATP7B gene might be considered as predictive
      markers for the efficacy evaluation of platinum-based chemotherapy in Chinese Han
      lung cancer patients.

PMID- 24852430
TI  - Tiam1 siRNA enhanced the sensitivity of sorafenib on esophageal squamous cell
      carcinoma in vivo.
AB  - Our previous study demonstrated that Tiam1 was highly expressed in esophageal
      squamous cell carcinoma (ESCC) tissues. In the present study, we investigated the
      therapeutic role of Tiam1 siRNA in combination with sorafenib in xenografted
      human ESCC. Our results demonstrated that expression of Tiam1 protein in EC9706
      cells was significantly higher than those in ESCC cells (Eca109 and EC1) and
      normal esophageal epithelial cells Het-1A (P < 0.05). Tiam1 siRNA markedly
      suppressed Tiam1 protein expression in tumor tissues of nude mice, but sorafenib
      did not alter Tiam1 level. In addition, Tiam1 siRNA or sorafenib alone evidently
      inhibited tumor growth, reduced Ki-67 proliferation index, and induced cell
      apoptosis in xenografted nude mice, and their combinations had the strongest
      effect. Notably, Tiam1 siRNA or sorafenib alone obviously increased p27 level,
      but reduced Mcl-1 and bcl-2 levels in xenografted nude mice, and their
      combinations reached the best effect. These findings suggest that combination of
      Tiam1 siRNA with sorafenib may be the novel molecular therapy target for the
      patients with ESCC.

PMID- 24852431
TI  - The specific methylation characteristics of cancer related genes in Chinese
      colorectal cancer patients.
AB  - Aberrant DNA methylation at CpG islands has been implicated as a critical player
      in colorectal cancer (CRC). However, its biological role and clinical
      significance in carcinogenesis have not been clearly clarified in Chinese CRC
      patients. In order to examine the methylation status of cancer-related genes in
      CRC progression, 184 tumor tissues were collected from Chinese patients diagnosed
      with CRC during 2008-2011. Promoter methylation was assessed by combined
      bisulphite-restriction analysis, methylation-specific PCR, and bisulphite
      sequencing PCR . The relationship between the gene promoter methylation status
      and clinicopathological factors/CRC mortality was examined by using the chi
      square test/Cox-proportional hazards models. Promoter hypermethylation of MLH1,
      p16, SFRP2, PHD3, KLOTHO, and IGFBP7 was observed in 1.6, 10.9, 97.3, 44.0, 59.8,
      and 88.6 % of CRC samples, respectively. KLOTHO promoter methylation reduced with
      age (P = 0.018) whereas p16 promoter methylation increased with age (P = 0.044)
      and was more frequent among males (P = 0.017). Tumor tissues (73.9 %) had
      concurrent methylation of two or more genes, with the most frequent combination
      as KLOTHO and IGFBP7 (53.8 %). Concurrent methylation of KLOTHO and IGFBP7
      occurred more frequently among patients less than 70 years old (P = 0.035) and
      those with poor differentiation (P = 0.024). CRC-specific mortality was not
      associated with promoter methylation and clinicopathological features except for
      age (P = 0.038; risk ratio (RR), 1.96; 95 % confidence interval (CI), 1.04-3.70)
      and TNM stage (P = 0.034; RR, 3.47; 95 % CI, 1.10-10.92). Methylation frequencies
      of MLH1, p16, PHD3, KLOTHO, and IGFBP7 in CRC tissues were significantly higher
      than that in the paired normal tissues, while promoter hypermethylation of SFRP2
      was widespread in normal tissues. In conclusion, we suggest that methylation of
      some genes (MLH1, PHD3, KLOTHO, p16, and IGFBP7) is important in CRC progression
      whereas SFRP2 methylation is unlikely to contribute to CRC development in Chinese
      patients. Besides, by identifying the characteristics of concordant methylation,
      we confirm the multifactorial nature of tumor progression.

PMID- 24852432
TI  - Revisiting the role of MCL1 in tumorigenesis of solid cancer: gene expression
      correlates with antiproliferative phenotype in breast cancer cells and its
      functional regulatory variants are associated with reduced cancer susceptibility.
AB  - Compared to the well-defined anti-apoptotic role of myeloid cell leukemia
      sequence 1 (MCL1), its antiproliferative function in tumorigenesis is less
      studied. We had recently reported that regulatory variants of MCL1 contribute to
      enhanced promoter activity but reduced risk of lung cancer. We hypothesized that
      MCL1 expression may manifest antiproliferative phenotype and its functional
      variations may have etiological relevance for breast cancer. We manipulated MCL1
      expression in MCF-7 cells and MDA231 with overexpression and knockdown, analyzed
      the effects on cell viability and cell cycling phase, and characterized the
      correlation with expression profiles of key regulators of cell cycle. We further
      genotyped the -190 insertion polymorphism and the neighboring single nucleotide
      polymorphisms (SNPs) in 745 breast cancer patients and 537 controls and analyzed
      their association with cancer risk. We confirmed that heightened expression of
      MCL1 resulted in decreased proliferation ability of breast cancer cells. We
      further observed that MCL1 overexpression in breast cancer cells resulted in cell
      cycle progression arresting in S phase and concomitant enhanced expression of
      p27, which could be rescued by p27 knockdown with co-transfection of small
      interfering RNA (siRNA). Furthermore, we found a significant reduction in breast
      cancer risk [odds ratio (OR) = 0.74; 95 % confidence interval (CI) = 0.59-0.93]
      associated with -190 insertion genotype; the expression-enhancing regulatory
      haplotype (OR 0.79; 95 % CI 0.66-0.95) and diplotype (OR 0.71; 95 % CI 0.57-0.89)
      were consistently associated with decreased cancer susceptibility. The study
      demonstrates that the expression-enhancing regulatory variants of MCL1 are
      protective modifiers of breast cancer risk, and reduced cell proliferation and
      arrested cell cycle progression partly mediated by p27 might be the underlying
      mechanism.

PMID- 24852433
TI  - Addressing uncertainties in renal transplantation: hypomagnesemia and the case of
      diabetes prevention.

PMID- 24852435
TI  - Life cycle assessment on microalgal biodiesel production using a hybrid
      cultivation system.
AB  - A life cycle assessment (LCA) was performed on a putative biodiesel production
      plant in which the freshwater alga Chlorella vulgaris, was grown using an
      existing system similar to a published commercial-scale hybrid cultivation. The
      hybrid system couples airlift tubular photobioreactors with raceway ponds in a
      two-stage process for high biomass growth and lipid accumulation. The results
      show that microalgal biodiesel production would have a significantly lower
      environmental impact than fossil-derived diesel. Based on the functional unit of
      1 ton of biodiesel produced, the hybrid cultivation system and hypothetical
      downstream process (base case) would have 42% and 38% savings in global warming
      potential (GWP) and fossil-energy requirements (FER) when compared to fossil
      derived diesel, respectively. Sensitivity analysis was performed to identify the
      most influential process parameters on the LCA results. The maximum reduction in
      GWP and FER was observed under mixotrophic growth conditions with savings of 76%
      and 75% when compared to conventional diesel, respectively. 

PMID- 24852436
TI  - Ethical issues of expert witness testimony.
AB  - Being a surgical expert witness (EW) in professional liability claims implies
      ethical responsibilities, which are usually unknown to the parties who try to
      obtain such testimony as well as to the surgeons involved in providing the expert
      opinion required by the courts. Giving medical testimony can be included in the
      field of surgery since (1) being an expert medical witness and judge the
      performance of another surgeon means that the witness must have a medical license
      and preferably be board-certified as a surgeon, and (2) the EW opinion sets the
      standard of care to be applied in each particular case. Thus, the role of the
      surgeon EW in the legal arena must have the same degree of integrity as the
      surgeon in his practice with direct patient care and it should be reviewed and
      subject to regulation. 

PMID- 24852434
TI  - Recent mitochondrial DNA mutations increase the risk of developing common late
      onset human diseases.
AB  - Mitochondrial DNA (mtDNA) is highly polymorphic at the population level, and
      specific mtDNA variants affect mitochondrial function. With emerging evidence
      that mitochondrial mechanisms are central to common human diseases, it is
      plausible that mtDNA variants contribute to the "missing heritability" of several
      complex traits. Given the central role of mtDNA genes in oxidative
      phosphorylation, the same genetic variants would be expected to alter the risk of
      developing several different disorders, but this has not been shown to date. Here
      we studied 38,638 individuals with 11 major diseases, and 17,483 healthy
      controls. Imputing missing variants from 7,729 complete mitochondrial genomes, we
      captured 40.41% of European mtDNA variation. We show that mtDNA variants
      modifying the risk of developing one disease also modify the risk of developing
      other diseases, thus providing independent replication of a disease association
      in different case and control cohorts. High-risk alleles were more common than
      protective alleles, indicating that mtDNA is not at equilibrium in the human
      population, and that recent mutations interact with nuclear loci to modify the
      risk of developing multiple common diseases. 

PMID- 24852437
TI  - Comparison of single-incision plus one additional port laparoscopy-assisted
      anterior resection with conventional laparoscopy-assisted anterior resection for
      rectal cancer.
AB  - BACKGROUND: Reduced-port laparoscopic surgery is the latest innovation in
      minimally invasive surgery. We performed single-incision plus one additional port
      laparoscopy-assisted anterior resection (SILS + 1-AR) starting in August 2010.
      This study aimed at evaluating the feasibility of SILS + 1-AR and comparing it
      with that of conventional laparoscopy-assisted anterior resection (C-AR).
      METHODS: Patients with preoperative clinical stage 0 to stage III rectal cancer
      were included. Demographic, intraoperative, and pathological examination data, as
      well as short-term outcome data, of 20 patients who underwent SILS + 1-AR were
      retrospectively compared with that of 20 patients who underwent C-AR.
      Invasiveness of the two procedures was also evaluated through a vital signs diary
      and hematological examination on postoperative days (POD) 1, 3, and 7. RESULTS:
      Operating time, mean estimated blood loss, the number of lymph nodes dissected,
      the number of lymph node metastases, and the mean distal resection margin length
      were not significantly different. However, postoperative neutrophil counts in the
      SILS + 1-AR group were lower than those in the C-AR group (P = 0.085). A
      significant difference in body temperature was observed in the SILS + 1-AR group
      on POD 1 (P = 0.028). No significant differences were observed in perioperative
      and overall morbidity between the two groups. Conversion to open surgery was
      required in 2 (10 %) of the 20 patients in the SILS + 1-AR group. The mean
      postoperative length of stay and recurrence rates were similar in the two groups.
      CONCLUSION: SILS + 1-AR for rectal cancer is similar to C-AR in safety,
      feasibility, and provision of oncological radicality.

PMID- 24852441
TI  - Concerted charge and energy transfer processes in a highly flexible fullerene-dye
      system: a mixed quantum-classical study.
AB  - Photoinduced excitation energy transfer and accompanying charge separation are
      elucidated for a supramolecular system of a single fullerene covalently linked to
      six pyropheophorbide-a dye molecules. Molecular dynamics simulations are
      performed to gain an atomistic picture of the architecture and the surrounding
      solvent. Excitation energy transfer among the dye molecules and electron transfer
      from the excited dyes to the fullerene are described by a mixed quantum-classical
      version of the Forster rate and the semiclassical Marcus rate, respectively. The
      mean characteristic time of energy redistribution lies in the range of 10 ps,
      while electron transfer proceeds within 150 ps. In between, on a 20 to 50 ps time
      scale, conformational changes take place in the system. This temporal hierarchy
      of processes guarantees efficient charge separation, if the structure is exposed
      to a solvent. The fast energy transfer can adopt the dye excitation to the actual
      conformation. In this sense, the probability to achieve charge separation is
      large enough since any dominance of unfavorable conformations that exhibit a
      large dye-fullerene distance is circumvented. And the slow electron transfer may
      realize an averaging with respect to different conformations. To confirm the
      reliability of our computations, ensemble measurements on the charge separation
      dynamics are simulated and a very good agreement with the experimental data is
      obtained. 

PMID- 24852439
TI  - Laser treatment for diabetic macular edema in the 21st century.
AB  - Diabetic macular edema (DME) is the leading cause of blindness in the diabetic
      population. The diabetes Control and Complications Trial reported that 27% of
      patients affected by type 1 diabetes develop DME within 9 years of onset. Other
      studies have shown that in patients with type 2 diabetes, the prevalence
      increased from 3% to 28% within 5 years of diagnosis to twenty years after the
      onset. At the present time, despite the enthusiasm for evaluating several new
      treatments for DME, including the intravitreal therapies for DME (e.g.,
      corticosteroids, and anti-VEGF drugs), laser photocoagulation remains the current
      gold standard and the only treatment with proven efficacy in a wide range of
      clinical trials for this condition. Despite being the standard technique for
      comparison and evaluation of the emerging treatments, we have generally poor
      understanding of the ETDRS recommendations, and we often forget about the results
      of laser in DME. The purpose of this review is to update our knowledge on laser
      photocoagulation for DME with an extensive review of the ETDRS results and
      discuss the laser techniques. Furthermore, we will describe the new developments
      in laser systems and review the current indications and results. Finally, we will
      discuss the results of laser treatments versus the current pharmacological
      therapies. We conclude by trying to provide a general overview that which laser
      treatment must be indicated and what types of lasers are currently recommended. 

PMID- 24852440
TI  - Weight-loss strategies used by the general population: how are they perceived?
AB  - BACKGROUND: The rising prevalence of obesity and the social pressure for thinness
      increase the prevalence of dieting. However, little is known about the overall
      perception of dieting strategies actually used by the general population.
      OBJECTIVES: Our main objective was to investigate perceptions of weight-loss
      practices in an observational study in order to identify the most favourable
      strategy. DESIGN: Adults from the ongoing Nutrinet-Sante cohort study who had
      reported engaging in dieting in the three previous years were included in the
      study. For each diet, detailed information was collected on types of diets,
      circumstances and perception of the diet, and outcomes. Perceptions were compared
      across diets using sex-specific mixed effects models. RESULT: Among the 48 435
      subjects who had completed the respective questionnaire, 12 673 (26.7%, 87.8% of
      women) had followed at least one weight-loss diet in the previous three years.
      Diet plans prescribed by health professionals and diets conforming to official
      dietary recommendations were the most favourably perceived among all assessed
      weight-loss strategies. Alternatively, commercial diet plans and self-imposed
      dietary restrictions were more negatively perceived (Odds ratios (OR) for
      adherence difficulty 1.30 (95% confidence interval (0.99;1.7)) in men and OR 1.92
      (1.76;2.10) in women compared to official nutritional guidelines; OR 1.06
      (0.82;1.38) in men and OR 1.39 (1.26;1.54) in women respectively) compared to
      official nutritional guidelines. CONCLUSION: Official dietary recommendations
      could be useful tools for maintaining a dietary balance while following a weight
      loss diet.

PMID- 24852442
TI  - Effects of erythromycin and rifampicin on immunomodulatory gene expression and
      cellular function in human polymorphonuclear leukocytes.
AB  - BACKGROUND: We investigated the effects of two antibiotics, erythromycin and
      rifampicin, on the immunomodulatory gene expression and cellular function of
      human polymorphonuclear leukocytes (PMNs). METHODS: We used real-time
      quantitative PCR to examine the expression of immunomodulatory genes. The
      production of reactive oxygen species (ROS) was determined by fluorescence
      activated cell sorting. PMN chemotaxis was analyzed using a KK chemotaxis
      chamber. RESULTS: Stimulation of PMNs with lipopolysaccharide (LPS) resulted in
      increases in the mRNA levels of immunomodulatory genes. Rifampicin significantly
      inhibited the overexpression of TLR2, TLR4, CD14 and IL8Rs. However, erythromycin
      suppressed only the upregulation of TLR2 and TNFA. Neither antibiotic had an
      effect on the production of ROS. Rifampicin significantly inhibited PMN
      chemotaxis, but erythromycin had no effect. CONCLUSIONS: Erythromycin and
      rifampicin may play anti-inflammatory roles by affecting the expression levels of
      immunomodulatory genes or the chemotaxis of PMNs.

PMID- 24852443
TI  - Highly shifted proton MR imaging: cell tracking by using direct detection of
      paramagnetic compounds.
AB  - PURPOSE: To explore the feasibility of tracking thulium (Tm)-1,4,7,10
      tetraazacyclododecane-alpha,alpha',alpha'',alpha'''-tetramethyl-1,4,7,10
      tetraacetic acid (DOTMA)-labeled cells in vivo by means of highly shifted proton
      magnetic resonance (MR) imaging as a potential alternative to established cell
      tracking methods. MATERIALS AND METHODS: All animal experiments were approved by
      the local ethics committee for animal experiments. Highly shifted proton MR
      imaging is based on the principle that the shifted resonances on Tm and
      dysprosium (Dy)-DOTMA can be detected separately from the tissue water signal at
      MR imaging with very short echo time and radial center-out readout (UTE, or
      "ultrashort echo time"). MR imaging of aqueous solutions and in mice in vivo was
      performed at 9.4 T. Human fibrosarcoma cells (HT-1080) and murine macrophages
      were labeled with different amounts of Tm-DOTMA. Labeled fibrosarcoma cells were
      injected subcutaneously into three mice. For cell tracking, labeled macrophages
      were administered intravenously into eight mice bearing local granulomatous
      inflammation. Three-dimensional UTE MR imaging was performed during 1 week.
      Macrophage viability and activity and fibrosarcoma cell viability were
      statistically analyzed by performing an unpaired two-tailed t test for labeled
      versus unlabeled cells by using data of at least six independent experiments.
      RESULTS: The strongly shifted MR lines of Tm- and Dy-DOTMA can be separated from
      the tissue water signal and from each other. A detection limit of about 25 umol/L
      of Tm-DOTMA was calculated from in vitro MR measurements. A mean +/- standard
      error of the mean intracellular uptake of (4.19 +/- 0.88) * 10(9) (HT-1080) and
      (10.1 +/- 3.0) * 10(10) (macrophages) of Tm-DOTMA molecules per cell was
      achieved. In vivo, Tm-DOTMA signal was detectable for 1 week in both tumors and
      macrophages, with a detection limit of approximately 10(4) HT-1080 and 600
      macrophages. Histologic examination results and elemental bioimaging confirmed
      labeled cells as source of MR signal. CONCLUSION: Strongly shifted proton three
      dimensional UTE MR imaging of Tm-DOTMA-labeled cells is a highly specific and
      sensitive tool for in vivo cell tracking.

PMID- 24852445
TI  - Meroterpenoids from the alga-derived fungi Penicillium thomii Maire and
      Penicillium lividum Westling.
AB  - Ten new austalide meroterpenoids (1-10) were isolated from the alga-derived fungi
      Penicillium thomii KMM 4645 and Penicillium lividum KMM 4663. Their structures
      were elucidated by extensive spectroscopic analysis and by comparison with
      related known compounds. The absolute configurations of some of the metabolites
      were assigned by the modified Mosher's method and CD data. Compounds 1, 2, 8, and
      9 were able to inhibit AP-1-dependent transcriptional activity in JB6 Cl41 cell
      lines at noncytotoxic concentrations. Austalides 1-5, 8, and 9 exhibited
      significant inhibitory activity against endo-1,3-beta-D-glucanase from a
      crystalline stalk of the marine mollusk Pseudocardium sachalinensis.

PMID- 24852446
TI  - Complications of negative pressure wound therapy: a mini review.
AB  - Negative pressure wound therapy, with its wide indications and narrow
      contraindications, has been widely used for various complicated wounds. Despite
      its excellent properties in promoting wound healing, there are sporadic but
      increasing reports on the complications. These complications included bleeding,
      infection, pain, rupture of the heart, and death in the short term. When used for
      the long term, the therapy may decrease life quality, increase anxiety, and lead
      to malnutrition. In this review, we briefly summarize the complications of
      negative pressure wound therapy. 

PMID- 24852444
TI  - Development of peptide-based lineage-specific serology for chronic Chagas
      disease: geographical and clinical distribution of epitope recognition.
AB  - BACKGROUND: Chagas disease, caused by infection with the protozoan Trypanosoma
      cruzi, remains a serious public health issue in Latin America. Genetically
      diverse, the species is sub-divided into six lineages, known as TcI-TcVI, which
      have disparate geographical and ecological distributions. TcII, TcV, and TcVI are
      associated with severe human disease in the Southern Cone countries, whereas TcI
      is associated with cardiomyopathy north of the Amazon. T. cruzi persists as a
      chronic infection, with cardiac and/or gastrointestinal symptoms developing years
      or decades after initial infection. Identifying an individual's history of T.
      cruzi lineage infection directly by genotyping of the parasite is complicated by
      the low parasitaemia and sequestration in the host tissues. METHODOLOGY/PRINCIPAL
      FINDINGS: We have applied here serology against lineage-specific epitopes of the
      T. cruzi surface antigen TSSA, as an indirect approach to allow identification of
      infecting lineage. Chagasic sera from chronic patients from a range of endemic
      countries were tested by ELISA against synthetic peptides representing lineage
      specific TSSA epitopes bound to avidin-coated ELISA plates via a biotin labelled
      polyethylene glycol-glycine spacer to increase rotation and ensure each amino
      acid side chain could freely interact with their antibodies. 79/113 (70%) of
      samples from Brazil, Bolivia, and Argentina recognised the TSSA epitope common to
      lineages TcII/TcV/TcVI. Comparison with clinical information showed that a higher
      proportion of Brazilian TSSApep-II/V/VI responders had ECG abnormalities than non
      responders (38% vs 17%; p<0.0001). Among northern chagasic sera 4/20 (20%) from
      Ecuador reacted with this peptide; 1/12 Venezuelan and 1/34 Colombian samples
      reacted with TSSApep-IV. In addition, a proposed TcI-specific epitope, described
      elsewhere, was demonstrated here to be highly conserved across lineages and
      therefore not applicable to lineage-specific serology. CONCLUSIONS/SIGNIFICANCE:
      These results demonstrate the considerable potential for synthetic peptide
      serology to investigate the infection history of individuals, geographical and
      clinical associations of T. cruzi lineages.

PMID- 24852447
TI  - Late cardiac effect of radiation therapy on a young woman with mediastinal
      Hodgkin's lymphoma.
AB  - We experienced an excision of the mediastinal tumor located in left anterior
      mediastinum found in a 21-year-old woman. The histologic diagnosis of Hodgkin's
      lymphoma was obtained. After operation, she was treated with mantle field
      radiotherapy (total 42 Gy) followed by chemotherapy. At 43-year old, she
      developed constrictive pericarditis and heart failure resulted in the late
      cardiac effects of mediastinal irradiation. Despite pericardiectomy followed by
      medical treatment, her cardiac symptoms gradually worsened and she died at 51
      year old. At autopsy, her heart was smaller than normal person. The residual
      pericardium and the surface of the myocardium had fibrous degeneration with tight
      adhesion and thickness that were dominant at the right atrium and ventricle.
      Likewise, we demonstrated that pericardiectomy scarcely led to a favorable
      outcome in this patient. These facts might be based on the radiation-associated
      cardiac effects involving any components of the cardiac structure. 

PMID- 24852448
TI  - Why parents refuse newborn hearing screening?

PMID- 24852449
TI  - Adherence to treatment guidelines for acute otitis media in children. The
      necessity of an effective strategy of guideline implementation.
AB  - OBJECTIVES: Acute otitis media is the single diagnosis responsible for most
      prescriptions of antibiotics in Sweden and the USA. The treatment of acute otitis
      media has significant impact on child health, healthcare costs, and the
      development of anti-microbial resistance. In the Swedish national guidelines from
      the year 2000, watchful waiting was recommended for most children over 2 years of
      age. The aims of the present study were to assess the degree of adherence to
      acute otitis media guidelines at a busy pediatric emergency department of a
      university hospital and to determine whether an information campaign changed the
      result. METHODS: Audit of 91 patient records before and 80 patient records after
      an information campaign consisting of an oral presentation, posting of flow
      charts, and sending of educational material to prescribing physicians. Four
      endpoints were studied: choosing to use antibiotics, choice of antibiotic, dosage
      of antibiotic, and duration of treatment. RESULTS: Before the information
      campaign, adherence to guidelines was between 70% (dosage) and around 90%
      (duration). No significant change was seen after the information campaign. The
      endpoint choosing to use antibiotics showed a large divergence in adherence in
      children under 2 years (96%) compared to older children (39%). CONCLUSIONS:
      Overall adherence to recommendations was 70-90% but adherence to watchful waiting
      was poor. Information did not improve adherence, suggesting insufficient
      educational power or the existence of barriers other than lack of knowledge.
      Specific barriers should be identified, and implementation and follow-up should
      be part of producing guidelines in order to achieve the desired results.

PMID- 24852450
TI  - All children with malignant rhabdoid tumors should be treated initially with
      intensive chemotherapy.
AB  - Malignant rhabdoid tumors (MRT) of soft tissues are aggressive tumors, which can
      be detected in almost any part of the body. MRT are rare, and very few cases have
      been reported in the literature. Prognosis of these tumors is extremely poor
      despite intensive therapy. Some risk factors such as young age or disseminated
      disease are associated with an aggressive and almost always lethal clinical
      course. Some clinicians even recommend initial palliative care due to this
      outcome. We report a case of metastatic MRT in a 6-month-old child with excellent
      initial response to chemotherapy. 

PMID- 24852451
TI  - Successful recruitment methods in the community for a two-site clinical trial.
AB  - Effective screening and recruitment are essential to the success of randomized
      clinical trials. This report is to describe key screening and recruitment
      strategies in a two site randomized clinical trial (RCT) conducted in community
      settings with a vulnerable chronically ill population and to suggest valuable
      approaches when planning trials. Differences between sites in a complex study
      with two considerably different environments (academic versus home care) and
      their participant pools presented challenges which required different screening
      and recruitment methods. A high level of communication between sites, creative
      problem solving and the ability to be flexible when problems were encountered
      were needed for successful screening and recruitment. 

PMID- 24852452
TI  - Teaching the teachers: faculty development in inter-professional education.
AB  - AIMS: The purpose of this study is to evaluate changes in self-concept for the
      knowledge, skills and attitudes toward inter-professional teamwork of
      facilitators who participated in training and an inter-professional team training
      event. BACKGROUND: Inter-professional education requires dedicated and educated
      faculty. METHODS: A pretest posttest quasi-experimental design was used for the
      evaluation. Fifty-three facilitators were asked to complete pre-post
      questionnaires to measure inter-professional team self-concept (IPTSC), assessing
      self-concept for the knowledge, skills, and attitudes required for performing in
      an inter-professional team. RESULTS: Post-session scores on inter-professional
      team knowledge, skills and attitudes were significantly higher (F(1, 31) = 5.59,
      p = .02). CONCLUSION: A facilitator development course and participation in the
      teaching event had a positive impact on perceived knowledge, skills and attitudes
      toward inter-professional teamwork.

PMID- 24852454
TI  - The first human laparoscopy and NOTES operation: Dimitrij Oscarovic Ott (1855
      1929).
AB  - Dimitrij Oscarovic Ott (1855-1929) can undoubtedly be called the true pioneer of
      laparoscopy, especially of natural orifice transluminal endoscopic surgery. In
      1901 already he performed abdominal examinations via a transvaginal access
      calling this procedure 'ventroscopy'. In 1902 the publication of his first
      results, as well as a description of the method and the equipment used, were
      released. In addition to Georg Kelling (1866-1945) and Hans Christian Jacobaeus
      (1879-1937), he therefore was one of the pioneers of present-day laparoscopy.
      Whereas Kelling published and presented his first results of merely animal trials
      in 1901 and Jacobaeus performed his first interventions on humans only in 1910,
      Ott had already used his new method in clinical practice since 1901. By only one
      incision in the cul-de-sac and utilizing a head lamp system similar to reflector
      lamps used by otolaryngologists, he inspected the abdominal cavity making use of
      a gynecological speculum. The patient was positioned in an extreme head-down
      position; for better lighting he used an additional light source which was
      connected to the speculum. Nowadays in Russia Prof. Ott still is a legend,
      especially in St. Petersburg. He was the director of the National Institute of
      Obstetrics and the personal physician to Empress Aleksandra Fedorovna (1872
      1918). He is regarded as the father of the Russian school of obstetrics and
      gynecology as well as the founder of endoscopic surgery and laparoscopy in
      Russia.

PMID- 24852453
TI  - Diagnostic ability of %p2PSA and prostate health index for aggressive prostate
      cancer: a meta-analysis.
AB  - The role of [-2]proPSA (p2PSA) based diagnostic tests for the detection of
      aggressive prostate cancer (PCa) has not been fully evaluated. We conducted a
      meta-analysis to evaluate the diagnostic performance of p2PSA/free PSA (%p2PSA)
      and prostate health index (Phi) tests for PCa and to evaluate their ability in
      discriminating between aggressive and non-aggressive PCa. A total of 16 articles
      were included in this meta-analysis. For the detection of PCa, the pooled
      sensitivity, specificity, and AUC were 0.86 (95% CI, 0.84-0.87), 0.40 (95% CI,
      0.39-042) and 0.72 (95% CI, 0.67-0.77) for %p2PSA respectively, and were 0.85
      (95% CI, 0.83-0.86), 0.45 (95% CI, 0.44-0.47) and 0.70 (95% CI=0.65-0.74) for
      Phi, respectively. In addition, the sensitivity for discriminating PCa between
      higher Gleason score (>=7) and lower Gleason score (<7) was 0.96 (95% CI, 0.93
      0.98) and 0.90 (95% CI, 0.87-0.92) for %p2PSA and Phi respectively, and the
      specificity was low, only 0.09 (95% CI, 0.06-0.12) and 0.17 (95% CI, 0.14-0.19)
      for %p2PSA and Phi, respectively. Phi and %p2PSA have a high diagnostic accuracy
      rates and can be used in PCa diagnosis. Phi and %p2PSA may be useful as tumor
      markers in predicating patients harboring more aggressive disease and guiding
      biopsy decisions.

PMID- 24852455
TI  - All-atom structures and calcium binding sites of the bacterial photosynthetic LH1
      RC core complex from Thermochromatium tepidum.
AB  - Computationally derived structures of the photosynthetic core complex composed of
      the light-harvesting (LH) system LH1 and the reaction center (RC) from a
      thermophilic purple sulfur bacterium Thermochromatium tepidum are reported
      providing first models of the LH1 system at atomic resolution. We used the known
      primary structure of alpha and beta polypeptides from this particular LH1 complex
      and the related bacterial LH templates to design the LH1 torus composed of 16
      alphabeta subunits trapping bacteriochlorophyll (BChl-a) dimers and carotenoid
      molecules. The macromolecule of RC was placed in the center of the ring and the
      LH1-RC complex was inserted inside the lipid bilayer to simulate the membrane
      environment. Since thermal stability of the LH1-RC complex is linked to Ca(2+)
      binding by the complex, location of trapping sites of calcium ions in the LH1
      polypeptides is examined by using molecular dynamics simulations of the entire
      system solvated in water with CaCl2 molecules in the system. The newly predicted
      Ca(2+) trapping sites can be responsible for attractive interaction of
      neighboring alphabeta subunits of LH1 with relevance to stability of the calcium
      bound LH1-RC complex. 

PMID- 24852456
TI  - The diets of school-aged Aboriginal youths in Canada: a systematic review of the
      literature.
AB  - BACKGROUND: Most national surveys examining diet leave large segments of the
      Aboriginal population under-represented. The present study aimed to: (i) review
      primary research studies that investigated the dietary intakes of Canadian school
      aged Aboriginal youths; (ii) summarise the tools and methodologies currently used
      to measure diet in this population; and (iii) identify knowledge gaps and suggest
      areas of future research. METHODS: A systematic review of research published
      between January 2004 and January 2014 related to the diets of Canadian school
      aged (6-18 years) Aboriginal youths was undertaken, including Medline, Scopus,
      ERIC, Web of Science and Google Scholar databases. Studies were summarised based
      on purpose, year, sample population, setting, dietary assessment method and main
      findings. RESULTS: Twenty-four studies were reviewed, all of which were cross
      sectional in design. Most (n = 16; 67%) were from Ontario or Quebec, investigated
      the diets of First Nations (n = 21; 88%) youths and took place in remote or
      isolated settings (n = 18; 75%). Almost all of the studies used the 24-h recall
      to assess intake (n = 19; 79%), of which 89% used a single recall. The findings
      suggest that the diets of Aboriginal youths could be improved. Of particular
      concern are inadequate intakes of vegetables and fruit, milk and alternatives,
      fibre, folate, vitamin A, vitamin C, calcium and vitamin D, concomitant with an
      excess consumption of sugar sweetened beverages, snacks and fast foods.
      Traditional foods remain important but tend to be consumed infrequently.
      CONCLUSIONS: The diets of Canadian Aboriginal youths are energy-dense and
      nutrient-poor. The diets of Inuit and Metis youths, in particular, and
      perceptions of a balanced diet warrant further investigation.

PMID- 24852457
TI  - Simultaneous EEG-fMRI: trial level spatio-temporal fusion for hierarchically
      reliable information discovery.
AB  - Simultaneous electroencephalography (EEG) and functional magnetic resonance
      imaging (fMRI) have been pursued in an effort to integrate complementary
      noninvasive information on brain activity. The primary goal involves better
      information discovery of the event-related neural activations at a spatial region
      of the BOLD fluctuation with the temporal resolution of the electrical signal.
      Many techniques and algorithms have been developed to integrate EEGs and fMRIs;
      however, the relative reliability of the integrated information is unclear. In
      this work, we propose a hierarchical framework to ensure the relative reliability
      of the integrated results and attempt to understand brain activation using this
      hierarchical ideal. First, spatial Independent Component Analysis (ICA) of fMRI
      and temporal ICA of EEG were performed to extract features at the trial level.
      Second, the maximal information coefficient (MIC) was adopted to temporally match
      them across the modalities for both linear and non-linear associations. Third,
      fMRI-constrained EEG source imaging was utilized to spatially match components
      across modalities. The simultaneously occurring events in the above two match
      steps provided EEG-fMRI spatial-temporal reliable integrated information,
      resulting in the most reliable components with high spatial and temporal
      resolution information. The other components discovered in the second or third
      steps provided second-level complementary information for flexible and cautious
      explanations. This paper contains two simulations and an example of real data,
      and the results indicate that the framework is a feasible approach to reveal
      cognitive processing in the human brain. 

PMID- 24852458
TI  - Radial, spiral and reverberating waves of spreading depolarization occur in the
      gyrencephalic brain.
AB  - OBJECTIVES: The detection of the hemodynamic and propagation patterns of
      spreading depolarizations (SDs) in the gyrencephalic brain using intrinsic
      optical signal imaging (IOS). METHODS: The convexity of the brain surface was
      surgically exposed in fourteen male swine. Within the boundaries of this window,
      brains were immersed and preconditioned with an elevated K(+) concentration (7
      mmol/l) in the standard Ringer lactate solution for 30-40 min. SDs were triggered
      using 3-5 MUl of 1 mol/l KCl solution. Changes in tissue absorbency or reflection
      were registered with a CCD camera at a wavelength of 564 nm (14 nm FWHM), which
      was mounted 25 cm above the exposed cortex. Additional monitoring by
      electrocorticography and laser-Doppler was used in a subset of animals (n=7) to
      validate the detection of SD. RESULTS: Of 198 SDs quantified in all of the
      experiments, 187 SDs appeared as radial waves that developed semi-planar fronts.
      The morphology was affected by the surface of the gyri, the sulci and the pial
      vessels. Other SD patterns such as spirals and reverberating waves, which have
      not been described before in gyrencephalic brains, were also observed. Diffusion
      gradients created in the cortex surface (i.e., KCl concentrations), sulci,
      vessels and SD-SD interactions make the gyrencephalic brain prone to the
      appearance of irregular SD waves. CONCLUSION: The gyrencephalic brain is capable
      of irregular SD propagation patterns. The irregularities of the gyrencephalic
      brain cortex may promote the presence of re-entrance waves, such as spirals and
      reverberating waves.

PMID- 24852461
TI  - Local sleep spindle modulations in relation to specific memory cues.
AB  - Sleep spindles have been connected to memory processes in various ways. In
      addition, spindles appear to be modulated at the local cortical network level. We
      investigated whether cueing specific memories during sleep leads to localized
      spindle modulations in humans. During learning of word-location associations,
      words presented in the left and right visual hemifields were paired with
      different odors. By presenting a single odor during a subsequent nap, we aimed to
      selectively reactivate a subset of the studied material in sleeping subjects.
      During sleep, we observed topographically restricted spindle responses to memory
      cues, suggesting successful reactivation of specific memory traces. In
      particular, we found higher amplitude and greater incidence of fast spindles over
      posterior brain areas involved in visuospatial processing, contralateral to the
      visual field being cued. These results suggest that sleep spindles in different
      cortical areas reflect the reprocessing of specific memory traces. 

PMID- 24852459
TI  - Flexible modulation of network connectivity related to cognition in Alzheimer's
      disease.
AB  - Functional neuroimaging tools, such as fMRI methods, may elucidate the neural
      correlates of clinical, behavioral, and cognitive performance. Most functional
      imaging studies focus on regional task-related activity or resting state
      connectivity rather than how changes in functional connectivity across conditions
      and tasks are related to cognitive and behavioral performance. To investigate the
      promise of characterizing context-dependent connectivity-behavior relationships,
      this study applies the method of generalized psychophysiological interactions
      (gPPI) to assess the patterns of associative-memory-related fMRI hippocampal
      functional connectivity in Alzheimer's disease (AD) associated with performance
      on memory and other cognitively demanding neuropsychological tests and clinical
      measures. Twenty-four subjects with mild AD dementia (ages 54-82, nine females)
      participated in a face-name paired-associate encoding memory study. Generalized
      PPI analysis was used to estimate the connectivity between the hippocampus and
      the whole brain during encoding. The difference in hippocampal-whole brain
      connectivity between encoding novel and encoding repeated face-name pairs was
      used in multiple-regression analyses as an independent predictor for 10
      behavioral, neuropsychological and clinical tests. The analysis revealed
      connectivity-behavior relationships that were distributed, dynamically
      overlapping, and task-specific within and across intrinsic networks; hippocampal
      whole brain connectivity-behavior relationships were not isolated to single
      networks, but spanned multiple brain networks. Importantly, these spatially
      distributed performance patterns were unique for each measure. In general, out-of
      network behavioral associations with encoding novel greater than repeated face
      name pairs hippocampal-connectivity were observed in the default-mode network,
      while correlations with encoding repeated greater than novel face-name pairs
      hippocampal-connectivity were observed in the executive control network (p<0.05,
      cluster corrected). Psychophysiological interactions revealed significantly more
      extensive and robust associations between paired-associate encoding task
      dependent hippocampal-whole brain connectivity and performance on memory and
      behavioral/clinical measures than previously revealed by standard activity
      behavior analysis. Compared to resting state and task-activation methods, gPPI
      analyses may be more sensitive to reveal additional complementary information
      regarding subtle within- and between-network relations. The patterns of robust
      correlations between hippocampal-whole brain connectivity and behavioral measures
      identified here suggest that there are 'coordinated states' in the brain; that
      the dynamic range of these states is related to behavior and cognition; and that
      these states can be observed and quantified, even in individuals with mild AD. 

PMID- 24852460
TI  - Subject-specific functional parcellation via prior based eigenanatomy.
AB  - We present a new framework for prior-constrained sparse decomposition of matrices
      derived from the neuroimaging data and apply this method to functional network
      analysis of a clinically relevant population. Matrix decomposition methods are
      powerful dimensionality reduction tools that have found widespread use in
      neuroimaging. However, the unconstrained nature of these totally data-driven
      techniques makes it difficult to interpret the results in a domain where network
      specific hypotheses may exist. We propose a novel approach, Prior Based
      Eigenanatomy (p-Eigen), which seeks to identify a data-driven matrix
      decomposition but at the same time constrains the individual components by
      spatial anatomical priors (probabilistic ROIs). We formulate our novel solution
      in terms of prior-constrained l1 penalized (sparse) principal component analysis.
      p-Eigen starts with a common functional parcellation for all the subjects and
      refines it with subject-specific information. This enables modeling of the inter
      subject variability in the functional parcel boundaries and allows us to
      construct subject-specific networks with reduced sensitivity to ROI placement. We
      show that while still maintaining correspondence across subjects, p-Eigen
      extracts biologically-relevant and patient-specific functional parcels that
      facilitate hypothesis-driven network analysis. We construct default mode network
      (DMN) connectivity graphs using p-Eigen refined ROIs and use them in a
      classification paradigm. Our results show that the functional connectivity graphs
      derived from p-Eigen significantly aid classification of mild cognitive
      impairment (MCI) as well as the prediction of scores in a Delayed Recall memory
      task when compared to graph metrics derived from 1) standard registration-based
      seed ROI definitions, 2) totally data-driven ROIs, 3) a model based on standard
      demographics plus hippocampal volume as covariates, and 4) Ward Clustering based
      data-driven ROIs. In summary, p-Eigen incarnates a new class of prior-constrained
      dimensionality reduction tools that may improve our understanding of the
      relationship between MCI and functional connectivity. 

PMID- 24852462
TI  - Long-term cortisol levels measured in scalp hair of obese patients.
AB  - OBJECTIVE: In obese subjects a relatively high cortisol output in urine has been
      observed compared to nonobese individuals. However, cortisol levels in blood,
      saliva, and urine in association with obesity have been inconsistent across
      studies, possibly due to the high variability of systemic cortisol levels.
      Cortisol levels measured in scalp hair provide a marker for long-term cortisol
      exposure, and have been associated with cardiovascular disease in an elderly
      population and to disease course in Cushing's disease. We aimed to compare hair
      cortisol levels between obese patients and nonobese controls. METHODS: Hair
      cortisol levels of 47 obese patients (median BMI 38.8, range 31.1-65.8), 41
      overweight, and 87 normal-weight subjects using an enzyme-linked immunosorbent
      assay (ELISA) were measured. RESULTS: Obese patients had higher hair cortisol
      levels than overweight and normal weight subjects (respectively 30.8 vs 8.5 and
      8.4 pg/mg hair, P < 0.001). No significant difference in hair cortisol levels was
      found between normal weight and overweight subjects. CONCLUSIONS: Our results
      suggest a higher long-term cortisol exposure in obese patients, which may
      contribute to cardiovascular disease risk. Future research will determine whether
      long-term cortisol levels provide a novel treatment target in the management of
      cardiovascular disease risk in obesity.

PMID- 24852463
TI  - Evaluation and management of hypertension in the perioperative period of Mohs
      micrographic surgery: a review.
AB  - BACKGROUND: While patients' hypertensive problems are usually actively and
      effectively managed by their primary physician, the dermatologic surgeon can
      still be affected by hypertension where the condition is unrecognized or
      uncontrolled. Hypertension is an important contributor to both bleeding and
      hematoma formation during and after surgery, ultimately affecting functional and
      cosmetic outcomes. OBJECTIVE: To extensively review the literature on
      perioperative management of the hypertensive patient as relates to the
      dermatologic surgeon. MATERIALS AND METHODS: An updated and comprehensive
      literature review, focusing on current diagnostic guidelines, practice by
      specific dermatologic surgery groups and management recommendations, was
      conducted. RESULTS: Review of the literature does support generalized guidelines
      for the management of hypertensive patients in the Mohs Micrographic Surgery
      (MMS) setting; however data on implementation and outcomes by specific
      dermatologic surgery groups is variable and lacking. CONCLUSIONS: The treatment
      of nonmelanoma skin cancers with MMS is now routine, and fortunately can be
      performed quite safely. There are still improvements to be made however, in
      managing perioperative hypertension-both in making patients aware of their
      condition and in treating it effectively. Practicing these measures can promote
      patients' overall health and the efficiency of the dermatologic surgeon's
      practice.

PMID- 24852464
TI  - Five percent 5-fluorouracil in a cream or for superficial peels in the treatment
      of advanced photoaging of the forearms: a randomized comparative study.
AB  - BACKGROUND: The antimetabolite 5-fluorouracil (5-FU) is used for topical
      treatment of actinic keratosis. Overall improvement in the skin is also observed.
      Additionally, 5-FU was reported to be used for superficial peels. OBJECTIVES: To
      evaluate the efficacy and safety of 5% 5-FU cream compared with peels for
      photodamaged forearms. METHODS: This interventional, randomized, comparative,
      evaluator-blind study included 32 patients with severe photoaging of forearms.
      The regimens comprised either application of 5% 5-FU cream everyday for 4 weeks
      on 1 forearm and 4 weekly peels on the other. Efficacy assessment included:
      clinical photodamage scores, opinion of patients and investigators, and blind
      photographic evaluation by independent observers. Skin biopsies were performed
      for histologic and immunohistochemical analysis. Safety evaluation comprised
      observation of adverse events. RESULTS: Clinical and histologic findings
      confirmed the benefits of topical 5% 5-FU, in cream or peels, which improved skin
      appearance and decreased the dermal elastotic material. Immunohistochemistry
      showed reduced levels of epidermal p53 and increase in the level of procollagen
      I. Results were maintained after 6 months. Predictable adverse events occurred,
      with no differences between treatments. Patients reported better tolerability to
      peels. CONCLUSION: Five percent 5-FU cream or peels was safe and effective for
      the treatment of photodamaged forearms. Decreased epidermal p53 levels and new
      dermal collagen were confirmed.

PMID- 24852465
TI  - Clinical implications of the middle temporal vein with regard to temporal fossa
      augmentation.
AB  - BACKGROUND: The middle temporal vein (MTV) traverses the temporal fossa between
      the superficial and deep layers of the deep temporal fascia. During filler
      injection into a deficient temporal fossa, filling agents may be inadvertently
      injected into the MTV, which results in vascular complications. OBJECTIVE: To
      investigate the course of the MTV to enable safe filler injection in the temple
      area. MATERIALS AND MATERIALS: The course and diameter of the MTV were measured
      in 18 hemifaces from 9 Korean cadavers. RESULTS: The MTV was located 23.5 and
      18.5 mm above the zygomatic arch at the jugale and the zygion, respectively. The
      diameter of the MTV at its thickest point was 5.1 mm. A splitting and reuniting
      pattern, such that the MTV occupied more space than a single trunk, was observed
      in 28% of cases. CONCLUSION: We propose that the safest area for filler injection
      in temporal fossa augmentation is one finger width above the zygomatic arch.

PMID- 24852466
TI  - Treatment of atrophic scars with fractionated CO2 laser facilitating delivery of
      topically applied poly-L-lactic acid.
AB  - BACKGROUND: Atrophic scars represent a loss of collagen and a challenging
      reconstructive dilemma with disappointing traditional treatments. OBJECTIVE: To
      study the safety and efficacy of the treatment of atrophic scars using an
      ablative fractionated CO2 laser and topical poly-L-lactic acid (PLLA) immediately
      after to improve atrophic scars. MATERIALS AND METHODS: This was an uncontrolled,
      institutional review board-approved, prospective study evaluating the treatment
      of atrophic scars. Four blinded dermatologists evaluated a total of 20
      photographs taken at baseline and 3 months after the laser and PLLA treatments
      using the Modified Manchester Scar Scale. Four criteria were evaluated: (1)
      overall improvement, (2) improvement in scar atrophy, (3) improvement in scar
      color/dyschromia mismatch, and (4) improvement in scar contour. RESULTS: All 4
      observers accurately identified 76 of the 80 "before" and "after" photographs.
      Therefore, the blinded evaluating physicians agreed that at the 3-month follow-up
      visit, 95% of the scars had improved. Each criterion demonstrated an average
      improvement of at least 33%. CONCLUSION: The combination of using an ablative
      fractional CO2 laser and PLLA in the treatment of atrophic scars has a
      synergistic effect on their inherent properties in up-regulating new collagen
      synthesis to improve atrophic scars.

PMID- 24852467
TI  - Efficacy of pulsed dye laser versus intense pulsed light in the treatment of
      striae distensae.
AB  - BACKGROUND: Pulsed dye laser (PDL) and intense pulsed light (IPL) have been used
      to treat striae distensae. OBJECTIVE: To compare the difference between the
      treatment efficacy of PDL and IPL on striae distensae. MATERIALS AND METHODS:
      Twenty patients with age ranging from 15 to 42 years were included in this study.
      All patients were treated on one side of their bodies with PDL and on the other
      side with IPL for 5 sessions with a 4-week interval between the sessions. Skin
      biopsies were stained with hematoxylin and eosin, Masson trichrome, orcein,
      Alcian blue, and anticollagen I alpha1. RESULTS: After both PDL and IPL, striae
      width was decreased and skin texture was improved in a highly significant manner.
      Collagen expression was increased in a highly significant manner after PDL and
      IPL. However, PDL induced the expression of collagen I in a highly significant
      manner compared with IPL, where p values were <.001 and .193, respectively.
      Striae rubra gave a superior response with either PDL or IPL compared with striae
      alba, which was evaluated clinically by the width, color, and texture, although
      the histological changes could not verify this consequence. CONCLUSION: Both PDL
      and IPL can enhance the clinical picture of striae through collagen stimulation.

PMID- 24852468
TI  - High-intensity focused ultrasound for the reduction of subcutaneous adipose
      tissue using multiple treatment techniques.
AB  - BACKGROUND: High-intensity focused ultrasound (HIFU) is a noninvasive alternative
      to traditional invasive body sculpting procedures. OBJECTIVE: To assess the
      effectiveness and tolerability of HIFU treatment using high and low fluence
      settings with 2 treatment techniques, grid repeat (GR) and site repeat (SR).
      MATERIALS AND METHODS: Two multicenter studies were conducted. Subjects underwent
      1 HIFU treatment with 1 of 5 treatment protocols (total fluence, 150-180 J/cm).
      Primary end point was change from baseline in waist circumference (CBWC) at 12
      weeks. Secondary end points included CBWC at 4 and 8 weeks and investigator- and
      subject-assessed clinical improvement. Adverse events were monitored throughout
      the study. RESULTS: In the intent-to-treat (ITT) population, all subjects had a
      statistically significant mean circumferential reduction of -2.3 +/- 2.9 cm (p <
      .0001) from baseline at 12 weeks, with no significant differences among the 5
      treatment groups (ITT: p = .153). Analysis of secondary end points in the ITT
      population demonstrated a significant circumferential reduction starting as early
      as 4 weeks in all subjects (-1.1 +/- 1.9 cm, p < .0001). Most subjects in all
      treatment groups showed improvements at 12 weeks as rated by the investigators
      and subjects. CONCLUSION: High-intensity focused ultrasound treatment using
      either a low or high fluence setting in a GR or SR method is effective for
      circumferential waist reduction, resulting in statistically significant CBWC in
      all treatment groups.

PMID- 24852469
TI  - Twenty-four-week multicenter, evaluator-blinded clinical study of the efficacy
      and safety of a dextran filler in the treatment of nasolabial folds.
AB  - BACKGROUND: Cross-linked dextran shows complete degradation in the vital tissue
      and has characteristics of neocollagenesis. However, its efficacy as a dermal
      filler in treating facial soft tissue defects has not been investigated.
      OBJECTIVE: To evaluate the efficacy and safety of subcutaneous injection of a
      dextran filler in treating nasolabial folds for 24 weeks. METHODS AND MATERIALS:
      Twenty patients were enrolled in this 24-week multicenter, evaluator-blinded
      clinical study. Each patient received a single session of a dextran filler
      treatment in both nasolabial folds, and no touch-up injections were given.
      Treatment efficacy was evaluated by blinded investigators at 4, 12, and 24 weeks
      after baseline. Safety data were collected from patient diaries and interviews at
      each follow-up visit. RESULTS: There were significant improvements (p<.0001) in
      the Wrinkle Severity Rating Scale scores compared with those at baseline with a
      mean decrease of 1.50+/-0.51 at 24 weeks. Only 1 mild treatment-related adverse
      event was noted throughout the 24-week follow-up period. CONCLUSION: Cross-linked
      dextran-derived injectable filler is considered to be a favorable measure in
      tissue augmentation of the nasolabial folds. Further investigation is needed to
      demonstrate the long-term efficacy and safety of dextran fillers.

PMID- 24852470
TI  - Carbon dioxide laser perforation and extirpation of steatocystoma multiplex.
AB  - BACKGROUND: Steatocystoma multiplex (SM) is a rare condition that presents as
      multiple dermal cysts, the appearance of which can have a significant impact on
      the patients' quality of life. Treatment options for SM are limited to surgical
      excision. OBJECTIVE: To present our experience of treating 8 SM cases using a
      novel approach that uses the carbon dioxide (CO2) laser and to explore patients'
      views about the treatment. METHODS: Patients were identified from our records.
      All patients had multiple lesions treated using the CO2 laser in the super pulse
      mode that punctured the cyst. This was followed by extirpating the cyst wall and
      its contents using a small Volkmann's spoon. Treatment efficacy was assessed
      clinically and feedback from the patients was sought through a telephone
      interview. RESULTS: All patients showed significant clinical improvement with
      minimal scarring and low recurrence rates. High levels of patient satisfaction,
      which helped to significantly improve their quality of life, were reported with
      the CO2 laser treatment. CONCLUSION: CO2 laser perforation and extirpation is a
      successful approach for managing SM that results in high patient satisfaction.

PMID- 24852471
TI  - An interrater and intrarater reliability study of 3 photographic scales for the
      classification of perioral aesthetic features.
AB  - BACKGROUND: Validated aesthetic rating scales for the perioral area provide
      objective evaluations for clinical trials and practice. OBJECTIVE: To confirm the
      reliability of 3 scales for evaluating dermal filler and neurotoxin treatments of
      the perioral area. MATERIALS AND METHODS: Three lip-specific photographic scales
      were developed from standardized 2-dimensional images to evaluate Perioral Lines
      at Rest (POL), Oral Commissures (OCS), and Perioral Lines at Maximum Contraction
      (POLM) severity scales. Each 4-grade scale (none to severe) had 3 representative
      images per grade. Physician validators rated volunteers on each scale (2 rounds
      of live review). Volunteers provided 2 series of self-assessments. Physician and
      subject intrarater reliability were based on the comparison of round 1 and round
      2 scores (mean weighted kappa coefficient). Other measures were physician
      interrater agreement (intraclass correlation) and subject/physician interrater
      agreement (Pearson correlation). RESULTS: Physician intrarater agreement was
      almost perfect or substantial (POL, 0.725; OCS, 0.789; POLM, 0.826). Overall,
      physician interrater agreement was almost perfect for all 3 scales and ranged
      from moderate to substantial by grade. Subject intrarater agreement and
      subject/physician interrater agreement were substantial. CONCLUSION: All scales
      demonstrated a high degree of intrarater and interrater reliability during the
      validation process. Physician concordance was good; subject ratings were reliable
      and comparable to physician assessments.

PMID- 24852472
TI  - Who do you prefer? A study of public preferences for health care provider type in
      performing cutaneous surgery and cosmetic procedures in the United States.
AB  - BACKGROUND: The public preference for provider type in performing cutaneous
      surgery and cosmetic procedures is unknown in the United States. METHODS: An
      internet-based survey was administered to the lay public. Respondents were asked
      to select the health care provider (dermatologist, plastic surgeon, primary care
      physician, general surgeon, and nurse practitioner/physician's assistant) they
      mostly prefer to perform different cutaneous cosmetic and surgical procedures.
      RESULTS: Three hundred fifty-four respondents undertook the survey.
      Dermatologists were identified as the most preferable health care provider to
      evaluate and biopsy worrisome lesions on the face (69.8%), perform skin cancer
      surgery on the back (73.4%), perform skin cancer surgery on the face (62.7%), and
      perform laser procedures (56.3%) by most of the respondents. For filler
      injections, the responders similarly identified plastic surgeons and
      dermatologists (47.3% vs 44.6%, respectively) as the most preferred health care
      provider. For botulinum toxin injections, there was a slight preference for
      plastic surgeons followed by dermatologists (50.6% vs 38.4%). Plastic surgeons
      were the preferred health care provider for procedures such as liposuction
      (74.4%) and face-lift surgery (96.1%) by most of the respondents. CONCLUSION:
      Dermatologists are recognized as the preferred health care providers over plastic
      surgeons, primary care physicians, general surgeons, and nurse
      practitioners/physician's assistants to perform a variety of cutaneous cosmetic
      and surgical procedures including skin cancer surgery, on the face and body, and
      laser procedures. The general public expressed similar preferences for
      dermatologists and plastic surgeons regarding filler injections.

PMID- 24852473
TI  - A regional survey of purse-string sutures for partial and complete closure of
      Mohs surgical defects.
AB  - BACKGROUND: The purse-string suture is a method for partial and complete closure
      of circular surgical defects. OBJECTIVE: Short-term and long-term efficacy and
      cosmesis were assessed to evaluate the utility of purse-string closure as the
      sole method of closure of Mohs defects in different locations. MATERIALS AND
      METHODS: Sixty-six circular wounds from Mohs surgery were closed with a running
      intradermal suture traversing the circumference of the wound. Preoperative and
      immediate postoperative wound areas were measured. Long-term cosmetic appearance
      was also assessed. RESULTS: An immediate decrease in average wound area was
      observed, most notably in the neck and arm. Long-term cosmetic results were best
      in the head and neck and were remarkably similar for a given anatomic area.
      CONCLUSION: The purse-string suture is rapid, simple, and associated with little
      morbidity. In properly selected cases, it is an excellent alternative for partial
      and complete closure of circular defects resulting from Mohs surgery.

PMID- 24852474
TI  - Gender differences in tumor and patient characteristics in those undergoing Mohs
      surgery.
AB  - BACKGROUND: Nonmelanoma skin cancer is the most common cancer in the United
      States, and when indicated, Mohs micrographic surgery (MMS) is an effective
      method for tumor removal. Few studies have focused on gender-specific
      characteristics among those undergoing MMS. OBJECTIVE: To elucidate patient- and
      tumor-specific characteristics in female MMS patients. MATERIALS AND METHODS: We
      performed a retrospective chart review of 12,344 consecutive patients undergoing
      MMS from 2005 to 2012. RESULTS: There was a 1.5:1 male predominance in the
      presentation of basal cell carcinoma (BCC) for MMS. However, BCC comprised 72% of
      tumors in women compared with 63% in men. Presenting tumor sizes of BCCs were
      smaller in women (0.9 vs 1.2 cm, p < .01). Superficial BCCs were more common in
      women (p < .001). Women had fewer squamous cell carcinoma (p < .01) and squamous
      cell carcinoma in situ (p < .01). They were more likely to present with tumors on
      their legs and central facial areas, whereas men had more tumors on their scalps
      and ears. Plastic surgery referral was over twice as common in the female
      population (p < .01). CONCLUSION: In our data set, significant gender-specific
      differences were found in women compared with men undergoing MMS. These findings
      may be the result of discrepancies in sun exposure, protective behavior, and
      cosmetic concern.

PMID- 24852475
TI  - Nail surgery among Mohs surgeons: prevalence, safety, and practice patterns.
AB  - BACKGROUND: Among US dermatologists, Mohs surgeons perform most of the nail
      surgeries. The specific practice patterns and safety precautions have not been
      formally studied. OBJECTIVE: To study the practice patterns, safety precautions,
      and complications of this group when performing nail surgery. METHODS: A survey
      was sent electronically to all members of the American College of Mohs Surgery
      Listserv. The survey evaluated the demographics of the surgeons, the types of
      surgery performed, the techniques for obtaining a bloodless field, and
      complications. RESULTS: Those surgeons who performed more procedures in training
      tended to continue that practice and performed more surgeries when in practice,
      as did surgeons with greater time since completing fellowship. Complications were
      rare. CONCLUSION: The data herein support that nail surgeries performed by Mohs
      surgeons are safe, with minimal complications, despite a broad range of
      approaches to obtaining a bloodless field and with a variety of procedures
      performed.

PMID- 24852476
TI  - Lip reconstruction with a mucosal A-to-T flap, revisited.

PMID- 24852477
TI  - Clinical improvement of striae distensae in Korean patients using a combination
      of fractionated microneedle radiofrequency and fractional carbon dioxide laser.

PMID- 24852479
TI  - Treatment of a deep infantile hemangioma using a penetrating insulated
      electrosurgical electrode (sublation).

PMID- 24852478
TI  - Surgical approach to harpoon nail: a new variant of ingrowing toenail.

PMID- 24852480
TI  - Detection of the tumor margin of basal-cell carcinoma using dermoscopy and high
      frequency ultrasound with narrow pieces of surgical tape as skin markers.

PMID- 24852481
TI  - Using recombinant human epidermal growth factor for the successful treatment of
      an excisional wound without a primary closure.

PMID- 24852482
TI  - A case of metastatic dermatofibrosarcoma protuberans.

PMID- 24852483
TI  - Impact of the ENDORSE study results on thromboprophylaxis prescribing patterns in
      medical patients attending the emergency department.
AB  - AIMS: The aim of the study was to evaluate the impact of the ENDORSE study
      results on thromboprophylaxis prescribing patterns in medical patients attending
      the Emergency Department (ED) by assessing prescribing appropriateness at
      admission. METHODS: A cross-sectional, observational, descriptive study was
      designed and included all adult medical patients admitted from an ED between 20
      November 2012 and 26 November 2012 at a large tertiary hospital. Patients to whom
      anticoagulants were prescribed for therapeutic purposes, patients admitted to
      Intensive Care Unit or maternity wards were excluded. Prescribing appropriateness
      was assessed using the Padua Prediction Score (ACCP 2012 guideline) for
      thromboembolic risk assessment and the NICE model to determine risk of bleeding.
      The primary end-point was the adequacy of thromboprophylaxis prescribed at the ED
      according to the ACCP 2012 guideline. RESULTS: A total of 393 patients were
      examined and 207 patients were included in the study (53.1% were male) with a
      median age of 75.3 years. The most common diagnosis at admission was related to a
      respiratory disease (41.1%). In 34.8% of the patients (72 patients), the
      recommendation of prophylaxis according to ACCP 2012 guideline did not match with
      the prophylaxis prescribed at admission. Reasons for non-concordance were
      undertreatment (14.5%) and overtreatment (20.3%). CONCLUSIONS: The adequacy of
      thromboprophylaxis in high risk patients for VTE has improved compared with the
      ENDORSE study. However, the percentage of patients with discordant prescriptions
      remains high. Despite the existence of treatment omissions, this percentage has
      been overcome by patients overtreated.

PMID- 24852484
TI  - Diverse regulation of cardiac expression of relaxin receptor by alpha1- and beta1
      adrenoceptors.
AB  - PURPOSE: Relaxin, a new drug for heart failure therapy, exerts its cardiac
      actions through relaxin family peptide receptor 1 (RXFP1). Factors regulating
      RXFP1 expression remain unknown. We have investigated effects of activation of
      adrenoceptors (AR), an important modulator in the development and prognosis of
      heart failure, on expression of RXFP1 in rat cardiomyocytes and mouse left
      ventricles (LV). METHODS: Expression of RXFP1 at mRNA (real-time PCR) and protein
      levels (immunoblotting) was measured in cardiomyocytes treated with alpha- and
      beta-AR agonists or antagonists. RXFP1 expression was also determined in the LV
      of transgenic mouse strains with cardiac-restricted overexpression of alpha1A-,
      alpha1B- or beta2-AR. Specific inhibitors were used to explore signal pathways
      involved in alpha1-AR mediated regulation of RXFP1 in cardiomyocytes. RESULTS: In
      cultured cardiomyocytes, alpha1-AR stimulation resulted in 2-3 fold increase in
      RXFP1 mRNA (P < 0.001), which was blocked by specific inhibitors for protein
      kinase C (PKC) or mitogen-activated protein kinases/extracellular signal
      regulated kinases (MAPK/ERK). Activation of beta1-, but not beta2-AR,
      significantly inhibited RXFP1 expression (P < 0.001). Relative to respective wild
      type controls, RXFP1 mRNA levels in the LV of mice overexpressing alpha1A- or
      alpha1B-AR were increased by 3- or 10-fold, respectively, but unchanged in beta2
      AR transgenic hearts. Upregulation by alpha1-AR stimulation RXFP1 expression was
      confirmed at protein levels both in vitro and in vivo. CONCLUSIONS: Expression of
      RXFP1 was up-regulated by alpha1-AR but suppressed by beta-AR, mainly beta1-AR
      subtype, in cardiomyocytes. Future studies are warranted to characterize the
      functional significance of such regulation, especially in the setting of heart
      failure.

PMID- 24852485
TI  - Healthy aging in Finland: patients adhere well to chronic statin therapy and
      their doctors to the guidelines.

PMID- 24852489
TI  - Assessment of haematological and clinical pathology effects of blood
      microsampling in suckling and weaned juvenile rats.
AB  - Tail vein microsampling in juvenile rats for toxicokinetic assessment has the
      potential to significantly reduce satellite animal use. This paper explores the
      toxicological consequences of microsampling at various post natal day (PND) ages.
      METHODS: Microsamples were taken as follows: suckling pups, 10 pups/sex, 3*32MUL
      samples on PND19, euthanased PND20; weaned pups, 10 pups/sex, 6*32MUL samples on
      PND23 and PND37, euthanased PND38; and satellite pups, 3 pups/sex, 5*32MUL
      samples on PND14 and PND35, euthanased on PND36. At termination on PND20 or
      PND38, clinical pathology samples were obtained and spleen, liver and bone marrow
      were examined. There were 10 unsampled concurrent control animals for each
      experiment. RESULTS: Suckling animals: females showed a slight, statistically
      significant decrease in red blood cell count (0.94* of control; p<0.05) with
      slight decreases in haemoglobin and haematocrit. The suckling males showed a
      slight increase in reticulocyte counts (1.05* of control) plus a statistically
      significant, slight increase in relative splenic weight. Weanling animals: the
      only effect was decreased liver weight in the microsampled females. In both
      suckling and weanling experiments, all clinical pathology values were within the
      age control range. In the satellite pups microsampled on PND14, there was a
      statistically significant transient increase in bodyweight gain between PND17 and
      PND21. CONCLUSION: The nature of the toxicological effects of microsampling was
      as expected. The magnitude of effects does not preclude microsampling main test
      pups provided care is taken over study design and blood volume loss.

PMID- 24852486
TI  - Chronic social stress in puberty alters appetitive male sexual behavior and
      neural metabolic activity.
AB  - Repeated social subjugation in early puberty lowers testosterone levels. We used
      hamsters to investigate the effects of social subjugation on male sexual behavior
      and metabolic activity within neural systems controlling social and motivational
      behaviors. Subjugated animals were exposed daily to aggressive adult males in
      early puberty for postnatal days 28 to 42, while control animals were placed in
      empty clean cages. On postnatal day 45, they were tested for male sexual behavior
      in the presence of receptive female. Alternatively, they were tested for mate
      choice after placement at the base of a Y-maze containing a sexually receptive
      female in one tip of the maze and an ovariectomized one on the other. Social
      subjugation did not affect the capacity to mate with receptive females. Although
      control animals were fast to approach females and preferred ovariectomized
      individuals, subjugated animals stayed away from them and showed no preference.
      Cytochrome oxidase activity was reduced within the preoptic area and ventral
      tegmental area in subjugated hamsters. In addition, the correlation of metabolic
      activity of these areas with the bed nucleus of the stria terminalis and anterior
      parietal cortex changed significantly from positive in controls to negative in
      subjugated animals. These data show that at mid-puberty, while male hamsters are
      capable of mating, their appetitive sexual behavior is not fully mature and this
      aspect of male sexual behavior is responsive to social subjugation. Furthermore,
      metabolic activity and coordination of activity in brain areas related to sexual
      behavior and motivation were altered by social subjugation. 

PMID- 24852487
TI  - eIF2B is a decameric guanine nucleotide exchange factor with a gamma2epsilon2
      tetrameric core.
AB  - eIF2B facilitates and controls protein synthesis in eukaryotes by mediating
      guanine nucleotide exchange on its partner eIF2. We combined mass spectrometry
      (MS) with chemical cross-linking, surface accessibility measurements and homology
      modelling to define subunit stoichiometry and interactions within eIF2B and eIF2.
      Although it is generally accepted that eIF2B is a pentamer of five non-identical
      subunits (alpha-epsilon), here we show that eIF2B is a decamer. MS and cross
      linking of eIF2B complexes allows us to propose a model for the subunit
      arrangements within eIF2B where the subunit assembly occurs through catalytic
      gamma- and epsilon-subunits, with regulatory subunits arranged in asymmetric
      trimers associated with the core. Cross-links between eIF2 and eIF2B allow
      modelling of interactions that contribute to nucleotide exchange and its control
      by eIF2 phosphorylation. Finally, we identify that GTP binds to eIF2Bgamma,
      prompting us to propose a multi-step mechanism for nucleotide exchange. 

PMID- 24852490
TI  - Primary measures of dependence among menthol compared to non-menthol cigarette
      smokers in the United States.
AB  - Previously published studies provide somewhat inconsistent evidence on whether
      menthol in cigarettes is associated with increased dependence. The National
      Health and Nutrition Examination Survey, National Survey on Drug Use and Health,
      National Health Interview Survey, and Tobacco Use Supplement to the Current
      Population Survey collect data on current cigarette type preference and primary
      measures of dependence, and thus allow examination of whether menthol smokers are
      more dependent than non-menthol smokers. Analyses based on combined data from
      multiple administrations of each of these four nationally representative surveys,
      using three definitions for current smokers (i.e., smoked ?1day, ?10days and
      daily during the past month), consistently demonstrate that menthol smokers do
      not report smoking more cigarettes per day than non-menthol smokers. Moreover,
      two of the three surveys that provide data on time to first cigarette after
      waking indicate no difference in urgency to smoke among menthol compared to non
      menthol smokers, while the third suggests menthol smokers may experience a
      greater urgency to smoke; estimates from all three surveys indicate that menthol
      versus non-menthol smokers do not report a higher Heaviness of Smoking Index.
      Collectively, these findings indicate no difference in dependence among U.S.
      smokers who use menthol compared to non-menthol cigarettes.

PMID- 24852491
TI  - Health assessment of gasoline and fuel oxygenate vapors: micronucleus and sister
      chromatid exchange evaluations.
AB  - Micronucleus and sister chromatid exchange (SCE) tests were performed for vapor
      condensate of baseline gasoline (BGVC), or gasoline with oxygenates, methyl tert
      butyl ether (G/MTBE), ethyl tert butyl ether (G/ETBE), t-amyl methyl ether
      (G/TAME), diisopropyl ether (G/DIPE), t-butyl alcohol (TBA), or ethanol (G/EtOH).
      Sprague Dawley rats (the same 5/sex/group for both endpoints) were exposed to 0,
      2000, 10,000, or 20,000mg/m(3) of each condensate, 6h/day, 5days/week over
      4weeks. Positive controls (5/sex/test) were given cyclophosphamide IP, 24h prior
      to sacrifice at 5mg/kg (SCE test) and 40mg/kg (micronucleus test). Blood was
      collected from the abdominal aorta for the SCE test and femurs removed for the
      micronucleus test. Blood cell cultures were treated with 5MUg/ml
      bromodeoxyuridine (BrdU) for SCE evaluation. No significant increases in
      micronucleated immature erythrocytes were observed for any test material.
      Statistically significant increases in SCE were observed in rats given BGVC alone
      or in female rats given G/MTBE. G/TAME induced increased SCE in both sexes at the
      highest dose only. Although DNA perturbation was observed for several samples,
      DNA damage was not expressed as increased micronuclei in bone marrow cells.
      Inclusion of oxygenates in gasoline did not increase the effects of gasoline
      alone or produce a cytogenetic hazard.

PMID- 24852492
TI  - Testing the coherence between occupational exposure limits for inhalation and
      their biological limit values with a generalized PBPK-model: the case of 2
      propanol and acetone.
AB  - The coherence between occupational exposure limits (OELs) and their corresponding
      biological limit values (BLVs) was evaluated for 2-propanol and acetone. A
      generic human PBPK model was used to predict internal concentrations after
      inhalation exposure at the level of the OEL. The fraction of workers with
      predicted internal concentrations lower than the BLV, i.e. the 'false negatives',
      was taken as a measure for incoherence. The impact of variability and uncertainty
      in input parameters was separated by means of nested Monte Carlo simulation.
      Depending on the exposure scenario considered, the median fraction of the
      population for which the limit values were incoherent ranged from 2% to 45%.
      Parameter importance analysis showed that body weight was the main factor
      contributing to interindividual variability in blood and urine concentrations and
      that the metabolic parameters Vmax and Km were the most important sources of
      uncertainty. This study demonstrates that the OELs and BLVs for 2-propanol and
      acetone are not fully coherent, i.e. enforcement of BLVs may result in OELs being
      violated. In order to assess the acceptability of this "incoherence", a maximum
      population fraction at risk of exceeding the OEL should be specified as well as a
      minimum level of certainty in predicting this fraction.

PMID- 24852493
TI  - Health assessment of gasoline and fuel oxygenate vapors: generation and
      characterization of test materials.
AB  - In compliance with the Clean Air Act regulations for fuel and fuel additive
      registration, the petroleum industry, additive manufacturers, and oxygenate
      manufacturers have conducted comparative toxicology testing on evaporative
      emissions of gasoline alone and gasoline containing fuel oxygenates. To mimic
      real world exposures, a generation method was developed that produced test
      material similar in composition to the re-fueling vapor from an automotive fuel
      tank at near maximum in-use temperatures. Gasoline vapor was generated by a
      single-step distillation from a 1000-gallon glass-lined kettle wherein
      approximately 15-23% of the starting material was slowly vaporized, separated,
      condensed and recovered as test article. This fraction was termed vapor
      condensate (VC) and was prepared for each of the seven test materials, namely:
      baseline gasoline alone (BGVC), or gasoline plus an ether (G/MTBE, G/ETBE,
      G/TAME, or G/DIPE), or gasoline plus an alcohol (G/EtOH or G/TBA). The VC test
      articles were used for the inhalation toxicology studies described in the
      accompanying series of papers in this journal. These studies included evaluations
      of subchronic toxicity, neurotoxicity, immunotoxicity, genotoxicity, reproductive
      and developmental toxicity. Results of these studies will be used for comparative
      risk assessments of gasoline and gasoline/oxygenate blends by the US
      Environmental Protection Agency.

PMID- 24852494
TI  - Metals in cosmetics: an a posteriori safety evaluation.
AB  - According to EU Regulation No. 1223/2009/CE cosmetic products for daily use can
      contain 'technically unavoidable traces' of metals. This definition is too vague.
      Authorities should set well-defined limits, considering the risks associated with
      metal contamination of personal care products (PCPs). This paper characterizes
      the risk arising from a number of metals (antimony, arsenic, cadmium, cobalt,
      chromium, mercury, nickel, lead) that may occur in 'unavoidable traces" in raw
      materials and, consequently, in PCPs. A 'worst case scenario' was adopted, based
      on the following assumptions: (i) the individual ingredients contained the
      maximum amount in traces allowed for each metal; (ii) the hypothetical PCP was
      produced exclusively with that single ingredient; (iii) when absorption through
      the skin was not known, data related to oral absorption were used. Risk
      characterization was performed calculating the Systemic Exposure Dosage (SED) and
      the Margin of Safety (MoS=NOAEL or BMDL10/SED). Exposure to the allegedly
      'technically unavoidable' maximum amounts of metals in cosmetic ingredients
      resulted in MoSs exceeding 100 (safety threshold) with one exception. This
      suggests that the availability of experimental dermal absorption rates could
      enable significant improvement in MoS, thus increasing safety levels. Although
      results are reassuring, the authors recommend minimization of contamination,
      according to the state of the art of manufacturing methods.

PMID- 24852495
TI  - Effect of captopril on collagen metabolisms in keloid fibroblast cells.
AB  - BACKGROUND: Keloid is a proliferative disease of fibrous tissues. The mechanism
      and consistently effective treatments of keloid remained unknown. Although there
      was a report about treating keloid with topical captopril, the further
      investigation about captopril affecting keloid has not been performed so far.
      OBJECTIVES: The aim of this study was to analyse the effect of captopril on
      collagen metabolisms in keloid fibroblast cells, and to provide information for
      the mechanism and therapy of keloid. METHODS: To investigate the effects and
      relative mechanism of captopril on keloid fibroblast cells, we examined the
      changes of collagen metabolism, expression of angiotensin, transforming growth
      factor (TGF)-beta1, platelet-derived growth factor (PDGF)-BB and heat shock
      protein 47 (HSP47), and cellular proliferation in keloid fibroblast cells.
      RESULTS: We found that all collagen metabolisms, expression of TGF-beta1, PDGF-BB
      and HSP47, and cellular proliferation decreased significantly with effective
      captopril concentrations in keloid fibroblast cells. CONCLUSIONS: With a
      comprehensive analysis of test results, we proposed that captopril may decrease
      the expression of angiotensin, PDGF-BB, TGF-beta1 and HSP47, and further inhibit
      proliferation and collagen synthesis of keloid fibroblast cells, which were the
      key in keloid formation.

PMID- 24852496
TI  - Psychometric properties of the parent and teacher ADHD Rating Scale (ADHD-RS):
      measurement invariance across gender, age, and informant.
AB  - Attention deficit/hyperactivity disorder (ADHD) is one of the most common
      psychiatric disorders in childhood and adolescence. Rating the severity of
      psychopathology and symptom load is essential in daily clinical practice and in
      research. The parent and teacher ADHD-Rating Scale (ADHD-RS) includes inattention
      and hyperactivity/impulsivity subscales and is one of the most frequently used
      scales in treatment evaluation of children with ADHD. An extended version, mADHD
      RS, also includes an oppositional defiant disorder subscale. The partial credit
      Rasch model, which is based on item response theory, was used to test the
      psychometric properties of this scale in a sample of 566 Danish school children
      between 6 and 16 years of age. The results indicated that parents and teachers
      had different frames of reference when rating symptoms in the mADHD-RS. There was
      support for the unidimensionality of the three subscales when parent and teacher
      ratings were analyzed independently. Nonetheless, evidence for differential item
      functioning was found across gender and age for specific items within each of the
      subscales. The findings expand existing psychometric information about the mADHD
      RS and support its use as a valid and reliable measure of symptom severity when
      used in age- and gender-stratified materials. 

PMID- 24852498
TI  - Effects of psychotherapy on trauma-related cognitions in posttraumatic stress
      disorder: a meta-analysis.
AB  - In the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders
      criteria for posttraumatic stress disorder (PTSD) incorporate trauma-related
      cognitions. This adaptation of the criteria has consequences for the treatment of
      PTSD. Until now, comprehensive information about the effect of psychotherapy on
      trauma-related cognitions has been lacking. Therefore, the goal of our meta
      analysis was to determine which psychotherapy most effectively reduces trauma
      related cognitions. Our literature search for randomized controlled trials
      resulted in 16 studies with data from 994 participants. We found significant
      effect sizes favoring trauma-focused cognitive-behavioral therapy as compared to
      nonactive or active nontrauma-focused control conditions of Hedges' g = 1.21, 95%
      CI [0.69, 1.72], p < .001 and g = 0.36, 95% CI [0.09, 0.63], p = .009,
      respectively. Treatment conditions with elements of cognitive restructuring and
      treatment conditions with elements of exposure, but no cognitive restructuring
      reduced trauma-related cognitions almost to the same degree. Treatments with
      cognitive restructuring had small advantages over treatments without cognitive
      restructuring. We concluded that trauma-focused cognitive-behavioral therapy
      effectively reduces trauma-related cognitions. Treatments comprising either
      combinations of cognitive restructuring and imaginal exposure and in vivo
      exposure, or imaginal exposure and in vivo exposure alone showed the largest
      effects. 

PMID- 24852497
TI  - Aging increases distraction by auditory oddballs in visual, but not auditory
      tasks.
AB  - Aging is typically considered to bring a reduction of the ability to resist
      distraction by task-irrelevant stimuli. Yet recent work suggests that this
      conclusion must be qualified and that the effect of aging is mitigated by whether
      irrelevant and target stimuli emanate from the same modalities or from distinct
      ones. Some studies suggest that aging is especially sensitive to distraction
      within-modality while others suggest it is greater across modalities. Here we
      report the first study to measure the effect of aging on deviance distraction in
      cross-modal (auditory-visual) and uni-modal (auditory-auditory) oddball tasks.
      Young and older adults were asked to judge the parity of target digits (auditory
      or visual in distinct blocks of trials), each preceded by a task-irrelevant sound
      (the same tone on most trials-the standard sound-or, on rare and unpredictable
      trials, a burst of white noise-the deviant sound). Deviant sounds yielded
      distraction (longer response times relative to standard sounds) in both tasks and
      age groups. However, an age-related increase in distraction was observed in the
      cross-modal task and not in the uni-modal task. We argue that aging might affect
      processes involved in the switching of attention across modalities and speculate
      that this may due to the slowing of this type of attentional shift or a reduction
      in cognitive control required to re-orient attention toward the target's
      modality. 

PMID- 24852499
TI  - Biological properties and molecular targets of umbelliprenin--a mini-review.
AB  - 7-Prenyloxycoumarins are a group of secondary metabolites found mainly in plants
      belonging to the families Rutaceae and Apiaceae. Auraptene, umbelliprenin (UM),
      and 7-isopentenyloxycoumarin are some examples of prenylated coumarins. UM occurs
      in various edible plant species including celery, coriander, angelica, lemon, and
      particularly, Ferula species. Although UM was isolated more than 50 years ago,
      its biological activities have been studied since the last two decades. Besides
      anticancer activities, biological activities including anti-inflammatory,
      antioxidant, and antileishmanial activities have been reported from this natural
      compound. The present mini-review deals with the biological activities and
      mechanism of actions reported for UM. 

PMID- 24852501
TI  - Potent inhibition by ropivacaine of metastatic colon cancer SW620 cell invasion
      and NaV1.5 channel function.
AB  - BACKGROUND: Metastatic breast and colon cancer cells express neonatal and adult
      splice variants of NaV1.5 voltage-activated Na(+) channels (VASCs). Block of
      VASCs inhibits cell invasion. Local anaesthetics used during surgical tumour
      excision inhibit VASC activity on nociceptive neurones providing regional
      anaesthesia. Inhibition of VASCs on circulating metastatic cancer cells may also
      be beneficial during the perioperative period. However, ropivacaine, frequently
      used to provide analgesia during tumour resection, has not been tested on colon
      cancer cell VASC function or invasion. METHODS: We used reverse transcription
      polymerase chain reaction and sequencing to identify NaV1.5 variants in the SW620
      metastatic colon cancer cell line. Recombinant adult and neonatal NaV1.5 variants
      were expressed in human embryonic kidney cells. Voltage-clamp recordings and
      invasion assays were used to examine the effects of ropivacaine on recombinant
      NaV1.5 channels and the metastatic potential of SW620 cells, respectively.
      RESULTS: SW620 cells expressed adult and neonatal NaV1.5 variants, which had
      similar steady-state inactivation profiles, but distinctive activation curves
      with the neonatal variant having a V1/2 of activation 7.8 mV more depolarized
      than the adult variant. Ropivacaine caused a concentration-dependent block of
      both NaV1.5 variants, with IC50 values of 2.5 and 3.9 uM, respectively. However,
      the reduction in available steady-state current was selective for neonatal NaV1.5
      channels. Ropivacaine inhibited SW620 invasion, with a potency similar to that of
      inhibition of NaV1.5 channels (3.8 uM). CONCLUSIONS: Ropivacaine is a potent
      inhibitor of both NaV1.5 channel activity and metastatic colon cancer cell
      invasion, which may be beneficial during surgical colon cancer excision.

PMID- 24852503
TI  - Involuntary movements due to vitamin B12 deficiency.
AB  - Deficiency of vitamin B12 produces protean effects on the nervous system, most
      commonly neuropathy, myelopathy, cognitive and behavioural symptoms, and optic
      atrophy. Involuntary movements comprise a relatively rare manifestation of this
      readily treatable disorder. Both adults and infants deficient in vitamin B12 may
      present with chorea, tremor, myoclonus, Parkinsonism, dystonia, or a combination
      of these, which may precede diagnosis or become apparent only a few days after
      parenteral replacement therapy has begun. The pathogenesis of these movement
      disorders shows interesting parallels to certain neurodegenerative conditions.
      The clinical syndrome responds well to vitamin B12 supplementation in most cases,
      and an early diagnosis is essential to reverse the haematological and
      neurological dysfunction characteristic of this disorder. In this article, we
      elucidate the association of vitamin B12 deficiency with movement disorders in
      adults and in infants, discuss the pathogenesis of this association, review
      previously reported cases, and present a young adult male with severe generalized
      chorea that showed a salutary response to vitamin B12 supplementation. 

PMID- 24852500
TI  - Association between intraoperative electroencephalographic suppression and
      postoperative mortality.
AB  - BACKGROUND: Low bispectral index values frequently reflect EEG suppression and
      have been associated with postoperative mortality. This study investigated
      whether intraoperative EEG suppression was an independent predictor of 90 day
      postoperative mortality and explored risk factors for EEG suppression. METHODS:
      This observational study included 2662 adults enrolled in the B-Unaware or BAG
      RECALL trials. A cohort was defined with >5 cumulative minutes of EEG
      suppression, and 1:2 propensity-matched to a non-suppressed cohort (<=5 min
      suppression). We evaluated the association between EEG suppression and mortality
      using multivariable logistic regression, and examined risk factors for EEG
      suppression using zero-inflated mixed effects analysis. RESULTS: Ninety day
      postoperative mortality was 3.9% overall, 6.3% in the suppressed cohort, and 3.0%
      in the non-suppressed cohort {odds ratio (OR) [95% confidence interval (CI)]=2.19
      (1.48-3.26)}. After matching and multivariable adjustment, EEG suppression was
      not associated with mortality [OR (95% CI)=0.83 (0.55-1.25)]; however, the
      interaction between EEG suppression and mean arterial pressure (MAP) <55 mm Hg
      was [OR (95% CI)=2.96 (1.34-6.52)]. Risk factors for EEG suppression were older
      age, number of comorbidities, chronic obstructive pulmonary disease, and higher
      intraoperative doses of benzodiazepines, opioids, or volatile anaesthetics. EEG
      suppression was less likely in patients with cancer, preoperative alcohol, opioid
      or benzodiazepine consumption, and intraoperative nitrous oxide exposure.
      CONCLUSIONS: Although EEG suppression was associated with increasing anaesthetic
      administration and comorbidities, the hypothesis that intraoperative EEG
      suppression is a predictor of postoperative mortality was only supported if it
      was coincident with low MAP. CLINICAL TRIAL REGISTRATION: NCT00281489 and
      NCT00682825.

PMID- 24852502
TI  - Component reductions in oxygen delivery generate variable haemodynamic and stress
      hormone responses.
AB  - BACKGROUND: In clinical practice, global oxygen delivery (DO2) is often
      considered as a whole; however pathological and adaptive responses after a
      decrease in individual constituents of the DO2 equation (cardiac output,
      haemoglobin, oxyhaemoglobin saturation) are likely to be diverse. We hypothesized
      that an equivalent decrease in DO2 after reductions in each separate component of
      the equation would result in different haemodynamic, tissue oxygenation, and
      stress hormonal responses. METHODS: Anaesthetized, fluid-resuscitated male Wistar
      rats were subjected to circulatory, anaemic, or hypoxic hypoxia (by haemorrhage,
      isovolaemic haemodilution, and breathing a hypoxic gas mix, respectively),
      produced either rapidly over 5 min or graded over 30 min, to a targeted 50%
      decrease in global oxygen delivery. Sham-operated animals acted as controls.
      Measurements were made of haemodynamics, skeletal muscle tissue oxygen tension,
      blood gas analysis, and circulating stress hormone levels. RESULTS: Whereas
      haemorrhage generated the largest decrease in cardiac output, and the greatest
      stress hormone response, haemodilution had the most marked effect on arterial
      pressure. In contrast, rapid hypoxaemia produced a minor impact on global
      haemodynamics yet induced the greatest decrease in regional oxygenation. A
      greater degree of hyperlactataemia was observed with graded insults compared with
      those administered rapidly. CONCLUSIONS: Decreasing global oxygen delivery,
      achieved by targeted reductions in its separate components, induces varying
      circulatory, tissue oxygen tension, and stress hormone responses. We conclude
      that not all oxygen delivery is the same; this disparity should be emphasized in
      classical teaching and re-evaluated in patient management.

PMID- 24852505
TI  - Individualized physiotherapy in the treatment of patellofemoral pain.
AB  - BACKGROUND AND PURPOSE: Patellofemoral pain (PFP) is associated with a wide range
      of local and global physical factors possibly contributing to pain and thus
      requires detailed assessment and individualized treatment. Yet, no cohort study
      was found that assessed the value of individualized physiotherapy, probably
      because this approach lends itself to clinical practice but not to scientific
      research. Most studies focus on a 'knee' or 'hip' treatment approach irrespective
      of individual global differences in lower limb alignment, movement patterns and
      muscle tightness. Therefore, this study aimed to determine the effectiveness of
      supplementing local treatment of PFP with individualized treatment targeting
      global contributing factors. Secondarily it aimed to subgroup the patients
      according to variations in lower limb alignment/laxity, movement patterns,
      biarticular muscle tightness and joint degeneration. METHOD: Forty-one patients
      (60 knees) with PFP who had followed a programme of local quadriceps
      strengthening, quadriceps stretching and taping for one fortnight were prescribed
      an individualized programme based on assessment. This global assessment included
      lower limb postural alignment, movement patterns, muscle tightness and range of
      motion. Another fortnight's treatment was prescribed accordingly and included
      specific, individualized postural and movement retraining, stretching and
      functional weight-bearing, strengthening exercises. Seven outcome measures,
      namely four pain measures, isokinetic quadriceps strength, quadriceps length and
      eccentric knee control, assessed improvement. RESULTS: All outcome measures
      showed further significant improvement following individualized treatment (p <
      0.03). Patients fell into four broad physical subgroups: hypermobility (often
      with malalignment), hypomobility (with three of four tight muscle groups), faulty
      movement patterns (mostly dynamic knee valgus) and patellofemoral osteoarthritis.
      CONCLUSIONS: Individualized treatment supplementing local standard physiotherapy
      for PFP leads to further significant improvement over 2 weeks. This study
      highlights the importance of assessing patients globally in order to optimize
      treatment and ongoing improvement. Recognition of different subgroups may guide
      treatment that should include both local and deficit-targeted global treatment.

PMID- 24852504
TI  - Involvement of the Wbp pathway in the biosynthesis of Porphyromonas gingivalis
      lipopolysaccharide with anionic polysaccharide.
AB  - The periodontal pathogen Porphyromonas gingivalis has two different
      lipopolysaccharide (LPS) molecules, O-LPS and A-LPS. We have recently shown that
      P. gingivalis strain HG66 lacks A-LPS. Here, we found that introduction of a wild
      type wbpB gene into strain HG66 restored formation of A-LPS. Sequencing of the
      wbpB gene from strain HG66 revealed the presence of a nonsense mutation in the
      gene. The wbpB gene product is a member of the Wbp pathway, which plays a role in
      the synthesis of UDP-ManNAc(3NAc)A in Pseudomonas aeruginosa; UDP-ManNAc(3NAc)A
      is sequentially synthesized by the WbpA, WbpB, WbpE, WbpD and WbpI proteins. We
      then determined the effect of the PGN_0002 gene, a wbpD homolog, on the
      biosynthesis of A-LPS. A PGN_0002-deficient mutant demonstrated an A-LPS
      biosynthesis deficiency. Taken together with previous studies, the present
      results suggest that the final product synthesized by the Wbp pathway is one of
      the sugar substrates necessary for the biosynthesis of A-LPS. 

PMID- 24852506
TI  - Effect of heavy metals on growth response and antioxidant defense protection in
      Bacillus cereus.
AB  - Bacterial cells in aerobic environment generate reactive oxygen species which may
      lead to oxidative stress, induced by a wide range of environmental factors
      including heavy metals. In the present context an attempt has been made to
      determine the toxic impact of cadmium and copper on growth performance, oxidative
      stress, and relative level of antioxidant protection in Bacillus cereus. Outcome
      of this study suggests that both the metal ions depleted the growth rate in this
      organism with respect to time and concentration of the metal ions. CdCl2 exposure
      induced extracellular glutathione (GSH) production, whereas, its level was
      declined in response to CuSO4. Superoxide dismutase (SOD) activity and hydrogen
      peroxide (H2 O2 ) content was elevated under CdCl2 stress but the activity of
      catalase (CAT) was inhibited. In contrast, incubation of bacteria with CuSO4
      exhibited decreased SOD activity with concomitant rise in CAT activity and H2 O2
      content. We also observed elevation of intracellular GSH level in this bacteria
      following supplementation of N-acetyl cysteine (NAC) in the medium. Overall
      findings of this study indicated differential toxicity of CdCl2 and CuSO4 in
      inducing oxidative stress, depleting growth rate and the possible involvement of
      GSH and CAT in adaptive antioxidant response. 

PMID- 24852507
TI  - Multiple sclerosis genetics.
AB  - Genome-wide association studies have revolutionised the genetic analysis of
      multiple sclerosis. Through international collaborative efforts involving tens of
      thousands of cases and controls, more than 100 associated common variants have
      now been identified. These variants consistently implicate genes associated with
      immunological processes, overwhelmingly lie in regulatory rather than coding
      regions, and are frequently associated with other autoimmune diseases. The
      functional implications of these associated variants are mostly unknown; however,
      early work has shown that several variants have effects on splicing that result
      in meaningful changes in the balance between different isoforms in relevant
      tissues. Including the well established risk attributable to variants in genes
      encoding human leucocyte antigens, only about a quarter of reported heritability
      can now be accounted for, suggesting that a substantial potential for further
      discovery remains. 

PMID- 24852508
TI  - Transfemoral interfaces with vacuum assisted suspension comparison of gait,
      balance, and subjective analysis: ischial containment versus brimless.
AB  - OBJECTIVE: Investigate the effect of a brimless interface design compared with
      ischial ramus containment (IRC) of interfaces when using vacuum-assisted
      suspension (VAS) on transfemoral amputees (TFAs). DESIGN: Randomized experimental
      crossover. SETTING: Household, community, and clinic. PARTICIPANTS: Unilateral
      TFAs (N=12 enrolled, N=10 analyzed). Mean age: 42.9 years. Mean residual limb
      length: 60.3% of the sound side femur length. Participants' mean time as an
      amputee: 8.3 years and median AMP score: 43. INTERVENTIONS: (1) IRC VAS
      interface, and (2) brimless VAS interface. Average medial wall height for IRC
      interfaces was 0.7cm proximal to the distal-most aspect of the ischial tuberosity
      (IT). The medial wall on the brimless design was an average of 3.3cm distal to
      the distal-most aspect of the IT. MAIN OUTCOME MEASURES: Spatiotemporal gait
      parameters, limits of stability, four square step test, and subjective perception
      using the prosthetic evaluation questionnaire (PEQ). RESULTS: Step length was
      significantly improved towards the IRC (p=0.04), when calculating degree of
      asymmetry. Base of support was significantly narrowed toward the brimless
      (p=0.03). All subjective measures reached statistical significance in favor of
      improvement with the brimless design, compared to the IRC. CONCLUSIONS: The
      brimless design was equivalent to IRC in most gait and balance outcome measures.
      However, step length was more symmetrical toward the IRC while base of support
      was narrowed toward the brimless demonstrating mixed inconsistent performance
      changes. Further, the PEQ demonstrated significant subjective improvements in
      prosthetic related function and quality of life when participants used the
      brimless design. Brimless interface design may be a clinically viable choice.

PMID- 24852509
TI  - Association of endothelial lipase Thr111Ile polymorphism with proliferative
      retinopathy in type 2 diabetes patients.
AB  - AIM: Our previous study demonstrated that the endothelial lipase (EL) C.584C>T
      polymorphism (rs2000813, p.Thr111Ile) was significantly associated with diabetic
      retinopathy (DR). The present work was conducted to see if this specific variant
      of the EL gene was more specifically linked to the severity of DR. METHODS: This
      retrospective cohort study was based on a review of the institutional charts of
      287 type 2 diabetes patients (mean age = 59.7 years; mean BMI = 29.0 kg/m(2);
      mean HbA1c=8.4%) genotyped for the EL C.584C>T polymorphism (rs2000813,
      p.Thr111Ile). The stage of DR was also determined for each genotype (CC, CT, TT).
      RESULTS: On univariate analysis, the minor allele homozygote TT variant was
      significantly associated with severe DR (OR: 4.3; 95% CI: 1.4, 13.1) compared
      with the major CC homozygote. No significant result was found for the CT
      heterozygote. Multivariate analysis revealed an increased risk for TT homozygotes
      to present with severe non-proliferative DR (OR: 8.09; 95% CI: 1.23, 53.1) or
      proliferative DR. Other associations were not significant. CONCLUSION: Minor
      allele homozygosity for this EL variant (c.584C>T) could be a significant risk
      factor for developing severe, sight-threatening disease due to proliferative DR.
      Further prospective studies of this EL polymorphism in a larger population sample
      are needed to confirm these results.

PMID- 24852510
TI  - Glycaemic variability and ambient hyperglycaemia: how and when are they linked?

PMID- 24852511
TI  - Solitary fibrous tumour of the submandibular gland.

PMID- 24852512
TI  - Cystic parathyroid adenoma: Report of a case.

PMID- 24852513
TI  - Design and experimental analysis of a new malleovestibulopexy prosthesis using a
      finite element model of the human middle ear.
AB  - INTRODUCTION AND OBJECTIVE: Many designs of prostheses are available for middle
      ear surgery. In this study we propose a design for a new prosthesis, which
      optimises mechanical performance in the human middle ear and improves some
      deficiencies in the prostheses currently available. Our objective was to design
      and assess the theoretical acoustic-mechanical behaviour of this new total
      ossicular replacement prosthesis. METHODS: The design of this new prosthesis was
      based on an animal model (an iguana). For the modelling and mechanical analysis
      of the new prosthesis, we used a dynamic 3D computer model of the human middle
      ear, based on the finite elements method (FEM). RESULTS: The new
      malleovestibulopexy prosthesis design demonstrates an acoustical-mechanical
      performance similar to that of the healthy human middle ear. This new design also
      has additional advantages, such as ease of implantation and stability in the
      middle ear. CONCLUSIONS: This study shows that computer simulation can be used to
      design and optimise the vibroacoustic characteristics of middle ear implants and
      demonstrates the effectiveness of a new malleovestibulopexy prosthesis in
      reconstructing the ossicular chain.

PMID- 24852514
TI  - Gender-specific association between the COMT Val158Met polymorphism and openness
      to experience in panic disorder patients.
AB  - BACKGROUND: Because major depression and panic disorder are both more prevalent
      among females and since several lines of evidence suggest that genetic factors
      might influence an individual's vulnerability to panic disorder, gene-gender
      interactions are being examined in such psychiatric disorders and mental traits.
      A number of studies have suggested that specific genes, e.g. catechol-O
      methyltransferase (COMT), might lead to distinct clinical characteristics of
      panic disorder. METHOD: We compared gender-specific personality-related
      psychological factors of 470 individuals with panic disorder and 458 healthy
      controls in terms of their COMT Val158Met polymorphism and their scores on the
      Revised NEO Personality Inventory (NEO PI-R) and State-Trait Anxiety Inventory
      (STAI) with a 1-way analysis of covariance. RESULTS: In the male panic disorder
      patients, the NEO PI-R score for openness to experience was significantly lower
      in the Met/Met carrier group, whereas there was no such association among the
      female panic disorder patients or the male or female control groups. CONCLUSION:
      The gender-specific effect of the COMT genotype suggests that the COMT Val/Met
      genotype may influence a personality trait, openness to experience, in males with
      panic disorder.

PMID- 24852515
TI  - Conditioning techniques and ischemic reperfusion injury in relation to on-pump
      cardiac surgery.
AB  - OBJECTIVES: The objective was to investigate the potential protective effects of
      two conditioning methods, on myocardial ischemic and reperfusion injury in
      relation to cardiac surgery. DESIGN: Totally 68 patients were randomly assigned
      to either a control group (n = 23), a remote ischemic preconditioning (RIPC)
      group (n = 23) or a glucagon-like peptide-1 (GLP-1) analogue group (n = 22). The
      RIPC protocol consisted of three cycles of upper limb ischemia. The GLP-1
      analogue protocol consisted of intravenous infusion with exenatide. The primary
      endpoint was postoperative cardiac enzyme release. The other secondary endpoints
      were metabolic parameters related to myocardial ischemia, measured using
      microdialysis technique, as well as other operative- and postoperative data.
      RESULTS: Postoperative cardiac enzyme release indicated a possible beneficial
      effect of the interventions, but the difference did not reach statistical
      significance. RIPC showed a trend toward lower levels (p = 0.07). We managed to
      establish a functional myocardial microdialysis model, but we were unable to
      demonstrate clear protective effects. CONCLUSIONS: We were in this prospective
      randomized proof-of-concept trial, unable to show distinct protective effects of
      the studied conditioning methods. However, this trial can hopefully contribute to
      generate a productive discussion concerning limitations and future use of cardiac
      conditioning as well as microdialysis technique.

PMID- 24852516
TI  - Determination of toxic congeners of 17 PCDDs/PCDFs and 12 dl-PCBs using
      polyurethane foam passive air samplers in ten cities around Seoul.
AB  - Twenty-nine toxic congeners including 17 polychlorinated dibenzo-p-dioxins
      (PCDDs) and polychlorinated dibenzofurans (PCDFs) and 12 dioxin-like
      polychlorinated biphenyls (dl-PCBs) were determined using passive air samplers
      (PAS) at ten satellite cities of Seoul for two years. Chemical analysis was done
      by high resolution gas chromatography (HRGC) coupled with high resolution mass
      spectrometry (HRMS). The ten monitoring sites represent urban-residential,
      industrial, urban-rural mixed, and rural types of regions in Gyeonggi Province,
      Republic of Korea. The concentrations of PCDDs/PCDFs and dioxin-like PCBs ranged
      from 0.59 pg.day(-1) to 29.7 pg.day(-1) and from 3.44 pg.day(-1) to 99.7 pg.day(
      1), respectively with the highest values at industrial areas. The relative
      abundance of more toxic congeners (tetra- and penta-chlorinated PCDDs/PCDFs) was
      the highest in urban-rural mixed group despite the less emission sources than
      industrial group. It implies that this group was under the influence of fugitive
      emissions that have not yet been identified or regulated. This study reports the
      first attempt of atmospheric PCDDs/PCDFs and dl-PCB measurements with PAS in the
      monitoring network of Korea, which highlights the efficacy of PAS in continuous
      and long-term monitoring of those species particularly at regions that could
      easily slip out of environmental governance or of low accessibility to
      monitoring.

PMID- 24852517
TI  - Network identification of hormonal regulation.
AB  - Relations among hormone serum concentrations are complex and depend on various
      factors, including gender, age, body mass index, diurnal rhythms and secretion
      stochastics. Therefore, endocrine deviations from healthy homeostasis are not
      easily detected or understood. A generic method is presented for detecting
      regulatory relations between hormones. This is demonstrated with a cohort of
      obese women, who underwent blood sampling at 10 minute intervals for 24-hours.
      The cohort was treated with bromocriptine in an attempt to clarify how hormone
      relations change by treatment. The detected regulatory relations are summarized
      in a network graph and treatment-induced changes in the relations are determined.
      The proposed method identifies many relations, including well-known ones.
      Ultimately, the method provides ways to improve the description and understanding
      of normal hormonal relations and deviations caused by disease or treatment. 

PMID- 24852518
TI  - Joint effects of environmental exposures and familial susceptibility to lung
      cancer in Chinese never smoking men and women.
AB  - OBJECTIVES: Previous epidemiological studies had limited power to investigate the
      joint effects of individual environmental risk factors and familial
      susceptibility to lung cancer. This study aimed to address this shortcoming.
      METHODS: We recruited 345 never smoking lung cancer cases and 828 community
      referents. We developed a collective environmental exposure index by assigning a
      value of 1 to subjects at high risks regarding environmental risk factors and 0
      otherwise, and then summed over using weights equivalent to the excess odds
      ratio. Potential additive and multiplicative interactions between environmental
      exposure index and family cancer history were examined. RESULTS: Compared with
      "low environmental exposure and without family cancer history", the odds ratio
      was 6.80 (95% confidence interval = 3.31-13.98) for males who had high
      environmental exposures but without family cancer history, whereas it increased
      to 30.61 (95% confidence interval = 9.38-99.87) if they also had a positive
      family history. The corresponding associations became weaker in never smoking
      females. No multiplicative interaction was observed for both genders and an
      additive interaction was restricted among males. CONCLUSIONS: This study
      developed a novel environmental exposure index that offers sufficient interest
      deserving further studies on the interactions between environmental exposures and
      familial susceptibility to lung cancer risk.

PMID- 24852519
TI  - Genetic susceptibility, residential radon, and lung cancer in a radon prone area.
AB  - INTRODUCTION: Radon exposure has been classified as the second cause of lung
      cancer, after tobacco, and the first in never smokers. GSTM1 and GSTT1 genes
      deletion increase the risk of lung cancer. We aim to know whether the risk of
      lung cancer because of residential radon is modulated by these genetic
      polymorphisms. METHODS: Hospital-based, case-control study where cases had
      confirmed lung cancer. Cases and controls did not have previous neoplasm and were
      older than 30. Controls attended hospital for noncomplex surgery. We analyzed the
      results for the whole sample and separately for never/light smokers and
      moderate/heavy smokers. RESULTS: Seven-hundred and ninety-two participants were
      analyzed. GSTM1 and GSTT1 deletion conferred an odds ratio (OR) of 1.38 (95%
      confidence interval [CI] 0.93-2.04) and 1.13 (95% CI 0.70-1.82), respectively.
      Individuals with GSTM1 present and residential radon concentrations higher than
      148 Bq/m had an OR of 1.48 (95% CI 0.73-3.00), whereas those with GSTM1 deleted
      had an OR of 2.64 (95% CI 1.18-5.91) when compared with participants with GSTM1
      present and radon concentrations below 50 Bq/m3. Similar results were observed
      for GSTT1 deletion. These results were basically the same for the moderate/heavy
      smokers' subgroup. CONCLUSIONS: The absence of GSTM1 and GSTT1 genes increases
      the risk of lung cancer because of radon exposure. These genes might modulate the
      carcinogenic pathway of alpha radiation. Further studies are warranted analyzing
      this association in never smokers.

PMID- 24852520
TI  - Self-reported cardiovascular disease and the risk of lung cancer, the HUNT study.
AB  - INTRODUCTION: Inflammation is involved in development of lung cancer and
      cardiovascular disease (CVD), and we hypothesize that self-reported CVD is an
      independent risk factor for lung cancer. METHODS: Data from the Nord-Trondelag
      Health Study (1984-2008) linked to the Norwegian Cancer and Death Cause Registry
      were analyzed stratified by smoking status. In total, 97,087 persons (1,634,967
      person years) were included (never smokers 567,575 person years, former smokers
      295,685 person years, current smokers 444,922 person years, and unknown 326,785
      person years) and followed for an average of 15 years. The proportional hazard
      model was applied to estimate the hazard ratio (HR) with a 95% confidence
      interval (CI) for self-reported CVD on lung cancer incidence rate adjusted for
      age, sex, body mass index, burden of tobacco smoking and chronic cough with
      phlegm. RESULTS: 1080 cases of lung cancer (1.1%) occurred. A total of 5981
      (6.9%) participants had at baseline or developed during follow-up self-reported
      CVD. After adjusting for confounders, self-reported CVD was an independent risk
      factor for the development of lung cancer in former (HR [95% CI] 1.74 [1.11
      2.73]) and current smokers (HR [95% CI] 1.38 [1.04-1.83]), but not in never
      smokers (HR [95% CI] 0.87 [0.34-2.23]). CONCLUSIONS: Self-reported CVD was
      independently associated with increased occurrence of lung cancer in former and
      current smokers. CVD may be a novel risk factor for lung cancer screening.

PMID- 24852522
TI  - Communication: Imaging the effects of the antisymmetric-stretching excitation in
      the O(3P) + CH4(v3 = 1) reaction.
AB  - Effects of one-quantum excitation of the antisymmetric-stretching mode of CH4(v3
      = 1) on the O((3)P) + CH4 reaction were studied in a crossed-beam, ion-imaging
      experiment. In the post-threshold region, we found that (1) the product state
      distributions are dominated by the CH3(00) + OH(v' = 1) pair, (2) the product
      angular distributions extend toward sideways from the backward dominance of the
      ground-state reaction, and (3) vibrational excitation exerts a positive effect on
      reactivity, but translational energy is more efficient in promoting the rate of
      this central-barrier reaction. All major findings agree reasonably well with
      recent theoretical results. Some remaining questions are pointed out.

PMID- 24852523
TI  - Communication: Nanosize-induced restructuring of Sn nanoparticles.
AB  - Stabilities and structures of beta- and alpha-Sn nanoparticles are studied using
      density functional theory. Results show that beta-Sn nanoparticles are more
      stable. For both phases of Sn, nanoparticles smaller than 1 nm (~48 atoms) are
      amorphous and have a band gap between 0.4 and 0.7 eV. The formation of band gap
      is found to be due to amorphization. By increasing the size of Sn nanoparticles
      (1-2.4 nm), the degree of crystallization increases and the band gap decreases.
      In these cases, structures of the core of nanoparticles are bulk-like, but
      structures of surfaces on the faces undergo reconstruction. This study suggests a
      strong size dependence of electronic and atomic structures for Sn nanoparticle
      anodes in Li-ion batteries.

PMID- 24852524
TI  - Predictions for water clusters from a first-principles two- and three-body force
      field.
AB  - A new rigid-monomer three-body potential has been developed for water by fitting
      it to more than 70 thousand trimer interaction energies computed ab initio using
      coupled-cluster methods and augmented triple-zeta-quality basis sets. This
      potential was used together with a modified form of a previously developed two
      body potential and with a polarization model of four- and higher-body
      interactions to predict the energetics of the water trimer, hexamer, and 24-mer.
      Despite using the rigid-monomer approximation, these predictions agree better
      with flexible-monomer benchmarks than published results obtained with flexible
      monomer force fields. An unexpected finding of our work is that simple
      polarization models predict four-body interactions to within a few percent,
      whereas for three-body interactions these models are known to have errors on the
      order of 50%. 

PMID- 24852525
TI  - Biased gradient squared descent saddle point finding method.
AB  - The harmonic approximation to transition state theory simplifies the problem of
      calculating a chemical reaction rate to identifying relevant low energy saddle
      points in a chemical system. Here, we present a saddle point finding method which
      does not require knowledge of specific product states. In the method, the
      potential energy landscape is transformed into the square of the gradient, which
      converts all critical points of the original potential energy surface into global
      minima. A biasing term is added to the gradient squared landscape to stabilize
      the low energy saddle points near a minimum of interest, and destabilize other
      critical points. We demonstrate that this method is competitive with the dimer
      min-mode following method in terms of the number of force evaluations required to
      find a set of low-energy saddle points around a reactant minimum. 

PMID- 24852526
TI  - A unified model for simulating liquid and gas phase, intermolecular energy
      transfer: N2 + C6F6 collisions.
AB  - Molecular dynamics simulations were used to study relaxation of a vibrationally
      excited C6F6* molecule in a N2 bath. Ab initio calculations were performed to
      develop N2-N2 and N2-C6F6 intermolecular potentials for the simulations. Energy
      transfer from "hot" C6F6 is studied versus the bath density (pressure) and number
      of bath molecules. For the large bath limit, there is no heating of the bath. As
      C6F6* is relaxed, the average energy of C6F6* is determined versus time, i.e.,
      ?E(t)?, and for each bath density ?E(t)? is energy dependent and cannot be fit by
      a single exponential. In the long-time limit C6F6 is fully equilibrated with the
      bath. For a large bath and low pressures, the simulations are in the fixed
      temperature, independent collision regime and the simulation results may be
      compared with gas phase experiments of collisional energy transfer. The
      derivative d[?E(t)?]/dt divided by the collision frequency omega of the N2 bath
      gives the average energy transferred from C6F6* per collision ?DeltaE(c)?, which
      is in excellent agreement with experiment. For the ~100-300 ps simulations
      reported here, energy transfer from C6F6* is to N2 rotation and translation in
      accord with the equipartition model, with no energy transfer to N2 vibration. The
      energy transfer dynamics from C6F6* is not statistically sensitive to fine
      details of the N2-C6F6 intermolecular potential. Tests, with simulation ensembles
      of different sizes, show that a relatively modest ensemble of only 24
      trajectories gives statistically meaningful results.

PMID- 24852527
TI  - An inversion-relaxation approach for sampling stationary points of spin model
      Hamiltonians.
AB  - Sampling the stationary points of a complicated potential energy landscape is a
      challenging problem. Here, we introduce a sampling method based on relaxation
      from stationary points of the highest index of the Hessian matrix. We illustrate
      how this approach can find all the stationary points for potentials or
      Hamiltonians bounded from above, which includes a large class of important spin
      models, and we show that it is far more efficient than previous methods. For
      potentials unbounded from above, the relaxation part of the method is still
      efficient in finding minima and transition states, which are usually the primary
      focus of attention for atomistic systems. 

PMID- 24852528
TI  - Assessing the density functional theory-based multireference configuration
      interaction (DFT/MRCI) method for transition metal complexes.
AB  - We report an assessment of the performance of density functional theory-based
      multireference configuration interaction (DFT/MRCI) calculations for a set of 3d-
      and 4d-transition metal (TM) complexes. The DFT/MRCI results are compared to
      published reference data from reliable high-level multi-configurational ab initio
      studies. The assessment covers the relative energies of different ground-state
      minima of the highly correlated CrF6 complex, the singlet and triplet
      electronically excited states of seven typical TM complexes (MnO4(-), Cr(CO)6,
      [Fe(CN)6](4-), four larger Fe and Ru complexes), and the corresponding electronic
      spectra (vertical excitation energies and oscillator strengths). It includes
      comparisons with results from different flavors of time-dependent DFT (TD-DFT)
      calculations using pure, hybrid, and long-range corrected functionals. The
      DFT/MRCI method is found to be superior to the tested TD-DFT approaches and is
      thus recommended for exploring the excited-state properties of TM complexes.

PMID- 24852529
TI  - The Nose-Hoover looped chain thermostat for low temperature thawed Gaussian wave
      packet dynamics.
AB  - We have used a generalised coherent state resolution of the identity to map the
      quantum canonical statistical average for a general system onto a phase-space
      average over the centre and width parameters of a thawed Gaussian wave packet. We
      also propose an artificial phase-space density that has the same behaviour as the
      canonical phase-space density in the low-temperature limit, and have constructed
      a novel Nose-Hoover looped chain thermostat that generates this density in
      conjunction with variational thawed Gaussian wave-packet dynamics. This forms a
      new platform for evaluating statistical properties of quantum condensed-phase
      systems that has an explicit connection to the time-dependent Schrodinger
      equation, whilst retaining many of the appealing features of path-integral
      molecular dynamics. 

PMID- 24852530
TI  - Coherence penalty functional: a simple method for adding decoherence in Ehrenfest
      dynamics.
AB  - We present a new semiclassical approach for description of decoherence in
      electronically non-adiabatic molecular dynamics. The method is formulated on the
      grounds of the Ehrenfest dynamics and the Meyer-Miller-Thoss-Stock mapping of the
      time-dependent Schrodinger equation onto a fully classical Hamiltonian
      representation. We introduce a coherence penalty functional (CPF) that accounts
      for decoherence effects by randomizing the wavefunction phase and penalizing
      development of coherences in regions of strong non-adiabatic coupling. The
      performance of the method is demonstrated with several model and realistic
      systems. Compared to other semiclassical methods tested, the CPF method
      eliminates artificial interference and improves agreement with the fully quantum
      calculations on the models. When applied to study electron transfer dynamics in
      the nanoscale systems, the method shows an improved accuracy of the predicted
      time scales. The simplicity and high computational efficiency of the CPF approach
      make it a perfect practical candidate for applications in realistic systems. 

PMID- 24852531
TI  - Two-dimensional fluorescence-detected coherent spectroscopy with absolute phasing
      by confocal imaging of a dynamic grating and 27-step phase-cycling.
AB  - We present a novel experimental scheme for two-dimensional fluorescence-detected
      coherent spectroscopy (2D-FDCS) using a non-collinear beam geometry with the aid
      of "confocal imaging" of dynamic (population) grating and 27-step phase-cycling
      to extract the signal. This arrangement obviates the need for distinct
      experimental designs for previously developed transmission detected non-collinear
      two-dimensional coherent spectroscopy (2D-CS) and collinear 2D-FDCS. We also
      describe a novel method for absolute phasing of the 2D spectrum. We apply this
      method to record 2D spectra of a fluorescent dye in solution at room temperature
      and observe "spectral diffusion." 

PMID- 24852532
TI  - Evolution of the vibrational spectra of doped hydrogen clusters with pressure.
AB  - The evolution of the vibrational spectra of the isoelectronic hydrogen clusters
      H26, H24He, and H24Li(+) is determined with pressure. We establish the
      vibrational modes with collective character common to the clusters, identify
      their individual vibrational fingerprints and discuss frequency shifts in the
      giga-Pascal pressure region. The results are of interest for the identification
      of doping elements such as inert He and ionic Li(+) in hydrogen under confinement
      or, conversely, establish the pressure of doped hydrogen when the vibrational
      spectrum is known. At high pressure, the spectra of the nanoclusters resemble the
      spectrum of a solid, and the nanoclusters may be considered crystals of nanometer
      scale. The computations are performed at the gradient-corrected level of density
      functional theory. The investigation is the first of its kind. 

PMID- 24852533
TI  - Line-space description of resonant four-wave mixing: theory for isotropic
      molecular states.
AB  - Based on the quantum Liouville formalism, a theory of the two-color, triply
      resonant four-wave mixing is developed for molecules with isotropically oriented
      angular momenta. The approach allows to strictly incorporate the relaxation
      matrices Gamma((r)) (r = 0, 1, 2) into the third-order susceptibility chi((3))
      whose expression acquires therewith the form of a scalar product in the line
      space. Thanks to this representation, isolation of all resonance terms from
      chi((3)) becomes a routine task. Some of these terms correspond to the case when
      a molecule initially interacts with two pump photons of the same frequency. Such
      interactions give rise to the grating line-space vectors which have the same
      (zero) eigenfrequency. Due to this degeneracy, the latter are easily mixed by
      rotationally inelastic collisions which shows up in a state-resolved coherence
      transfer. The satellite signals induced thereby provide a great scope to study
      the state-to-state inelastic rates in situ by purely optical means. If the
      diagonal form of Gamma is assumed, the satellites become forbidden and our
      results reduce to conventional expressions for the main resonances. Polarization
      configurations are designed for direct measurements of the population (r = 0),
      orientation (r = 1), and alignment (r = 2) contributions to chi((3)). Finally,
      depending on the photon-molecule interaction sequence, the resonance terms of
      chi((3)) are shown to be differently affected by velocity averaging, the effect
      which conspicuously manifests itself when Doppler broadening becomes paramount. 

PMID- 24852534
TI  - Isotope effects and spectroscopic assignments in the non-dissociative
      photoionization spectrum of N2.
AB  - Photoionization efficiency spectra of (14)N2, (15)N(14)N, and (15)N2 from 15.5 to
      18.9 eV were measured using synchrotron radiation at the Advanced Light Source at
      Lawrence Berkeley National Laboratory with a resolution of 6 meV, and significant
      changes in peak energies and intensities upon isotopic substitution were
      observed. Previously, we reported the isotope shifts and their applications to
      Titan's atmosphere. Here, we report more extensive experimental details and
      tabulate the isotope shifts of many transitions in the N2 spectrum, including
      those for (15)N(14)N, which have not been previously reported. The isotope shifts
      are used to address several long-standing ambiguities in spectral peak
      assignments just above the ionization threshold of N2. The feature at 15.677 eV
      (the so-called second "cathedral" peak) is of particular interest in this
      respect. The measured isotope shifts for this peak relative to (14)N2 are 0.015
      +/- 0.001 eV for (15)N2 and 0.008 +/- 0.001 eV for (15)N(14)N, which match most
      closely with the isotope shifts predicted for transitions to the (A (2)Piu v' =
      2)4ssigma(g) (1)Pi(u) state using Herzberg equations for the isotopic differences
      in harmonic oscillator energy levels plus the first anharmonic correction of
      0.0143 eV for (15)N2 and 0.0071 eV for (15)N(14)N. More generally, the isotope
      shifts measured for both (15)N2 and (15)N(14)N relative to (14)N2 provide new
      benchmarks for theoretical calculations of interferences between direct and
      indirect autoionization states which can interact to produce intricate resonant
      structures in molecular photoionization spectra in regions near ionization
      thresholds.

PMID- 24852535
TI  - Solid state 1H spin-lattice relaxation and isolated-molecule and cluster
      electronic structure calculations in organic molecular solids: the relationship
      between structure and methyl group and t-butyl group rotation.
AB  - We report ab initio density functional theory electronic structure calculations
      of rotational barriers for t-butyl groups and their constituent methyl groups
      both in the isolated molecules and in central molecules in clusters built from
      the X-ray structure in four t-butyl aromatic compounds. The X-ray structures have
      been reported previously. We also report and interpret the temperature dependence
      of the solid state (1)H nuclear magnetic resonance spin-lattice relaxation rate
      at 8.50, 22.5, and 53.0 MHz in one of the four compounds. Such experiments for
      the other three have been reported previously. We compare the computed barriers
      for methyl group and t-butyl group rotation in a central target molecule in the
      cluster with the activation energies determined from fitting the (1)H NMR spin
      lattice relaxation data. We formulate a dynamical model for the superposition of
      t-butyl group rotation and the rotation of the t-butyl group's constituent methyl
      groups. The four compounds are 2,7-di-t-butylpyrene, 1,4-di-t-butylbenzene, 2,6
      di-t-butylnaphthalene, and 3-t-butylchrysene. We comment on the unusual ground
      state orientation of the t-butyl groups in the crystal of the pyrene and we
      comment on the unusually high rotational barrier of these t-butyl groups. 

PMID- 24852536
TI  - Structural dynamics of phenylisothiocyanate in the light-absorbing excited
      states: resonance Raman and complete active space self-consistent field
      calculation study.
AB  - The excited state structural dynamics of phenyl isothiocyanate (PITC) after
      excitation to the light absorbing S2(A'), S6(A'), and S7(A') excited states were
      studied by using the resonance Raman spectroscopy and complete active space self
      consistent field method calculations. The UV absorption bands of PITC were
      assigned. The vibrational assignments were done on the basis of the Fourier
      transform (FT)-Raman and FT-infrared measurements, the density-functional theory
      computations, and the normal mode analysis. The A-, B-, and C-bands resonance
      Raman spectra in cyclohexane, acetonitrile, and methanol solvents were,
      respectively, obtained at 299.1, 282.4, 266.0, 252.7, 228.7, 217.8, and 208.8 nm
      excitation wavelengths to probe the corresponding structural dynamics of PITC.
      The results indicated that the structural dynamics in the S2(A'), S6(A'), and
      S7(A') excited states were very different. The conical intersection point
      CI(S2/S1) were predicted to play important role in the low-lying excited state
      decay dynamics. Two major decay channels were predicted for PITC upon excitation
      to the S2(A') state: the radiative S(2,min) -> S0 transition and the nonradiative
      S2 -> S1 internal conversion via CI(S2/S1). The differences in the decay dynamics
      between methyl isothiocyanate and PITC in the first light absorbing excited state
      were discussed. The role of the intersystem crossing point ISC(S1/T1) in the
      excited state decay dynamics of PITC is evaluated.

PMID- 24852537
TI  - Nuclear spin conversion of water inside fullerene cages detected by low
      temperature nuclear magnetic resonance.
AB  - The water-endofullerene H2O@C60 provides a unique chemical system in which freely
      rotating water molecules are confined inside homogeneous and symmetrical carbon
      cages. The spin conversion between the ortho and para species of the endohedral
      H2O was studied in the solid phase by low-temperature nuclear magnetic resonance.
      The experimental data are consistent with a second-order kinetics, indicating a
      bimolecular spin conversion process. Numerical simulations suggest the
      simultaneous presence of a spin diffusion process allowing neighbouring ortho and
      para molecules to exchange their angular momenta. Cross-polarization experiments
      found no evidence that the spin conversion of the endohedral H2O molecules is
      catalysed by (13)C nuclei present in the cages. 

PMID- 24852538
TI  - The zero-multipole summation method for estimating electrostatic interactions in
      molecular dynamics: analysis of the accuracy and application to liquid systems.
AB  - In the preceding paper [I. Fukuda, J. Chem. Phys. 139, 174107 (2013)], the zero
      multipole (ZM) summation method was proposed for efficiently evaluating the
      electrostatic Coulombic interactions of a classical point charge system. The
      summation takes a simple pairwise form, but prevents the electrically non-neutral
      multipole states that may artificially be generated by a simple cutoff
      truncation, which often causes large energetic noises and significant artifacts.
      The purpose of this paper is to judge the ability of the ZM method by
      investigating the accuracy, parameter dependencies, and stability in applications
      to liquid systems. To conduct this, first, the energy-functional error was
      divided into three terms and each term was analyzed by a theoretical error-bound
      estimation. This estimation gave us a clear basis of the discussions on the
      numerical investigations. It also gave a new viewpoint between the excess energy
      error and the damping effect by the damping parameter. Second, with the aid of
      these analyses, the ZM method was evaluated based on molecular dynamics (MD)
      simulations of two fundamental liquid systems, a molten sodium-chlorine ion
      system and a pure water molecule system. In the ion system, the energy accuracy,
      compared with the Ewald summation, was better for a larger value of multipole
      moment l currently induced until l ? 3 on average. This accuracy improvement with
      increasing l is due to the enhancement of the excess-energy accuracy. However,
      this improvement is wholly effective in the total accuracy if the theoretical
      moment l is smaller than or equal to a system intrinsic moment L. The simulation
      results thus indicate L ~ 3 in this system, and we observed less accuracy in l =
      4. We demonstrated the origins of parameter dependencies appearing in the
      crossing behavior and the oscillations of the energy error curves. With raising
      the moment l we observed, smaller values of the damping parameter provided more
      accurate results and smoother behaviors with respect to cutoff length were
      obtained. These features can be explained, on the basis of the theoretical error
      analyses, such that the excess energy accuracy is improved with increasing l and
      that the total accuracy improvement within l ? L is facilitated by a small
      damping parameter. Although the accuracy was fundamentally similar to the ion
      system, the bulk water system exhibited distinguishable quantitative behaviors. A
      smaller damping parameter was effective in all the practical cutoff distance, and
      this fact can be interpreted by the reduction of the excess subset. A lower
      moment was advantageous in the energy accuracy, where l = 1 was slightly superior
      to l = 2 in this system. However, the method with l = 2 (viz., the zero
      quadrupole sum) gave accurate results for the radial distribution function. We
      confirmed the stability in the numerical integration for MD simulations employing
      the ZM scheme. This result is supported by the sufficient smoothness of the
      energy function. Along with the smoothness, the pairwise feature and the
      allowance of the atom-based cutoff mode on the energy formula lead to the exact
      zero total-force, ensuring the total-momentum conservations for typical MD
      equations of motion. 

PMID- 24852539
TI  - Ab initio and relativistic DFT study of spin-rotation and NMR shielding constants
      in XF6 molecules, X = S, Se, Te, Mo, and W.
AB  - We present an analysis of the spin-rotation and absolute shielding constants of
      XF6 molecules (X = S, Se, Te, Mo, W) based on ab initio coupled cluster and four
      component relativistic density-functional theory (DFT) calculations. The results
      show that the relativistic contributions to the spin-rotation and shielding
      constants are large both for the heavy elements as well as for the fluorine
      nuclei. In most cases, incorporating the computed relativistic corrections
      significantly improves the agreement between our results and the well-established
      experimental values for the isotropic spin-rotation constants and their
      anisotropic components. This suggests that also for the other molecules, for
      which accurate and reliable experimental data are not available, reliable values
      of spin-rotation and absolute shielding constants were determined combining ab
      initio and relativistic DFT calculations. For the heavy nuclei, the breakdown of
      the relationship between the spin-rotation constant and the paramagnetic
      contribution to the shielding constant, due to relativistic effects, causes a
      significant error in the total absolute shielding constants. 

PMID- 24852540
TI  - Laser control of the radiationless decay in pyrazine using the dynamic Stark
      effect.
AB  - The laser control of the radiationless decay between the B(3u)(npi*) and
      B(2u)(pipi*) states of pyrazine using the dynamic Stark effect has been
      investigated. A vibronic coupling model Hamiltonian in diabatic representation,
      including potential energy, transition dipole, and static polarizability surfaces
      as a function of the four most important vibrational modes of the molecule has
      been parametrized using multi-reference electronic structure calculations. The
      interaction of the molecule with a strong non-resonant laser pulse has been
      analyzed in terms of dressed potential energy surfaces. Because of the large
      polarizability difference between the vibronically coupled B(3u)(npi*) and
      B(2u)(pipi*) states, the Stark effect induced by the non-resonant laser pulse
      shifts the conical intersection away from the Franck-Condon region. We have
      shown, by solving the time-dependent Schrodinger equation for the molecule
      interacting with a relatively weak pump pulse driving the electronic excitation
      from the ground state to the B(2u)(pipi*) state, and a strong non-resonant
      control pulse, that this control mechanism can be used to trap the wavepacket on
      the B(2u)(pipi*) potential energy surface for a much longer time than the natural
      B(2u)(pipi*) lifetime.

PMID- 24852541
TI  - Free energy of cluster formation and a new scaling relation for the nucleation
      rate.
AB  - Recent very large molecular dynamics simulations of homogeneous nucleation with
      (1 - 8) * 10(9) Lennard-Jones atoms [J. Diemand, R. Angelil, K. K. Tanaka, and H.
      Tanaka, J. Chem. Phys. 139, 074309 (2013)] allow us to accurately determine the
      formation free energy of clusters over a wide range of cluster sizes. This is now
      possible because such large simulations allow for very precise measurements of
      the cluster size distribution in the steady state nucleation regime. The peaks of
      the free energy curves give critical cluster sizes, which agree well with
      independent estimates based on the nucleation theorem. Using these results, we
      derive an analytical formula and a new scaling relation for nucleation rates: ln
      J'/eta is scaled by ln S/eta, where the supersaturation ratio is S, eta is the
      dimensionless surface energy, and J(') is a dimensionless nucleation rate. This
      relation can be derived using the free energy of cluster formation at equilibrium
      which corresponds to the surface energy required to form the vapor-liquid
      interface. At low temperatures (below the triple point), we find that the surface
      energy divided by that of the classical nucleation theory does not depend on
      temperature, which leads to the scaling relation and implies a constant, positive
      Tolman length equal to half of the mean inter-particle separation in the liquid
      phase.

PMID- 24852542
TI  - Simulation of the single-vibronic-level emission spectrum of HPS.
AB  - We have computed the potential energy surfaces of the X1A' and A1A" states of HPS
      using the explicitly correlated multi-reference configuration interaction (MRCI
      F12) method, and Franck-Condon factors between the two states, which include
      anharmonicity and Duschinsky rotation, with the aim of testing the assignment of
      the recently reported single-vibronic-level (SVL) emission spectrum of HPS [R.
      Grimminger, D. J. Clouthier, R. Tarroni, Z. Wang, and T. J. Sears, J. Chem. Phys.
      139, 174306 (2013)]. These are the highest level calculations on these states yet
      reported. It is concluded that our spectral simulation supports the assignments
      of the molecular carrier, the electronic states involved and the vibrational
      structure of the experimental laser induced fluorescence, and SVL emission
      spectra proposed by Grimminger et al. [J. Chem. Phys. 139, 174306 (2013)].
      However, there remain questions unanswered regarding the relative electronic
      energies of the two states and the geometry of the excited state of HPS.

PMID- 24852543
TI  - Electronic state spectroscopy of diiodomethane (CH2I2): experimental and
      computational studies in the 30,000-95,000 cm-1 region.
AB  - The electronic absorption spectrum of diiodomethane in the 30,000-95,000 cm(-1)
      region is investigated using synchrotron radiation; the spectrum in the 50,000
      66,500 cm(-1) region is reported for the first time. The absorption bands in the
      30,000-50,000 cm(-1) region are attributed to valence transitions, while the
      vacuum ultraviolet (VUV) spectrum (50,000-95,000 cm(-1)) is dominated by several
      Rydberg series converging to the first four ionization potentials of CH2I2 at
      9.46, 9.76, 10.21, and 10.56 eV corresponding to the removal of an electron from
      the outermost 3b2, 2b1, 1a2, and 4a1 non-bonding orbitals, respectively. Rydberg
      series of ns, np, and nd type converging to each of the four ionization
      potentials are assigned based on a quantum defect analysis. Time dependent
      density functional theory calculations of excited states support the analysis and
      help in interpretation of the Rydberg and valence nature of observed transitions.
      Density functional theory calculations of the neutral and ionic ground state
      geometries and vibrational frequencies are used to assign the observed vibronic
      structure. Vibronic features accompanying the Rydberg series are mainly due to
      excitation of the C-I symmetric stretch (nu3) and CH2 wag (nu8) modes, with
      smaller contributions from the C-H symmetric stretch (nu1). UV absorption bands
      are assigned to low lying valence states 1(1)B2, 1(1)B1, 2(1)A1, 3(1)A1, 2(1)B1,
      and 2(1)B2 and the unusually high underlying intensity in parts of the VUV
      spectrum is attributed to valence states with high oscillator strength. This is
      the first report of a comprehensive Rydberg series and vibronic analysis of the
      VUV absorption spectrum of CH2I2 in the 50,000-85,000 cm(-1) region. The VUV
      absorption spectrum of CD2I2 which serves to verify and consolidate spectral
      assignments is also reported here for the first time.

PMID- 24852544
TI  - Structure, solvation, and dynamics of Mg2+, Ca2+, Sr2+, and Ba2+ complexes with 3
      hydroxyflavone and perchlorate anion in acetonitrile medium: a molecular dynamics
      simulation study.
AB  - Molecular dynamics simulations of complexes of Mg(2+), Ca(2+), Sr(2+), and Ba(2+)
      with 3-hydroxyflavone (flavonol, 3HF) and ClO4- in acetonitrile were performed.
      The united atoms force field model was proposed for the 3HF molecule using the
      results of DFT quantum chemical calculations. 3HF was interpreted as a rigid
      molecule with two internal degrees of freedom, i.e., rotation of the phenyl ring
      and of the OH group with respect to the chromone moiety. The interatomic radial
      distribution functions showed that interaction of the cations with flavonol
      occurs via the carbonyl group of 3HF and it is accompanied with substitution of
      one of the acetonitrile molecules in the cations' first solvation shells.
      Formation of the cation-3HF complexes does not have significant impact on the
      rotation of the phenyl ring with respect to the chromone moiety. However, the
      orientation of the flavonol's OH-group is more sensitive to the interaction with
      doubly charged cations. When complex with Mg(2+) is formed, the OH-group turns
      out of the plane of the chromone moiety that leads to rupture of intramolecular H
      bond in the ligand molecule. Complexation of Ca(2+), Sr(2+), and BaClO4+ with 3HF
      produces two structures with different OH-positions, as in the free flavonol with
      the intramolecular H-bond and as in the complex with Mg(2+) with disrupted H
      bonding. It was shown that additional stabilization of the [MgClO4(3HF)](+) and
      [BaClO4(3HF)](+) complexes is determined by strong affinity of perchlorate anion
      to interact with flavonol via intracomplex hydrogen bond between an oxygen atom
      of the anion and the hydrogen atom of the 3-hydroxyl group. Noticeable difference
      in the values of the self-diffusion coefficients for Kt(2+) from one side and
      ClO4-, 3HF, and AN in the cations' coordination shell from another side implies
      quite weak interaction between cation, anion, and ligands in the investigated
      complexes.

PMID- 24852545
TI  - Fluctuating micro-heterogeneity in water-tert-butyl alcohol mixtures and lambda
      type divergence of the mean cluster size with phase transition-like multiple
      anomalies.
AB  - Water-tert-butyl alcohol (TBA) binary mixture exhibits a large number of
      thermodynamic and dynamic anomalies. These anomalies are observed at surprisingly
      low TBA mole fraction, with x(TBA) ~ 0.03-0.07. We demonstrate here that the
      origin of the anomalies lies in the local structural changes that occur due to
      self-aggregation of TBA molecules. We observe a percolation transition of the TBA
      molecules at x(TBA) ~ 0.05. We note that "islands" of TBA clusters form even
      below this mole fraction, while a large spanning cluster emerges above that mole
      fraction. At this percolation threshold, we observe a lambda-type divergence in
      the fluctuation of the size of the largest TBA cluster, reminiscent of a critical
      point. Alongside, the structure of water is also perturbed, albeit weakly, by the
      aggregation of TBA molecules. There is a monotonic decrease in the tetrahedral
      order parameter of water, while the dipole moment correlation shows a weak
      nonlinearity. Interestingly, water molecules themselves exhibit a reverse
      percolation transition at higher TBA concentration, x(TBA) ~ 0.45, where large
      spanning water clusters now break-up into small clusters. This is accompanied by
      significant divergence of the fluctuations in the size of largest water cluster.
      This second transition gives rise to another set of anomalies around. Both the
      percolation transitions can be regarded as manifestations of Janus effect at
      small molecular level.

PMID- 24852546
TI  - Carbon tetrachloride under extreme conditions.
AB  - We report on three experiments on carbon tetrachloride subjected to extreme
      conditions. In the first experiment, Raman spectra of CCl4 were acquired up to 28
      GPa. Evidence was observed for at least two new phases of CCl4 above 14 GPa
      (phase VI) and above 22 GPa (phase VII). Decompression of the sample showed no
      evidence of pressure-induced decomposition. In the second experiment, a
      synchrotron x-ray diffraction study was performed up to 30 GPa verifying phase V
      and potential phases above 14 (VI) and 22 GPa (VII), respectively. In the third
      study, we examined irradiated CCl4 using synchrotron infrared spectroscopy to
      reduce fluorescent contamination. Some sort of carbon allotrope appears as a
      byproduct suggesting the following reaction with hard x-rays: CCl4+ hnu -> C +
      2Cl2. 

PMID- 24852547
TI  - Enhanced flow of core-softened fluids through narrow nanotubes.
AB  - We investigate through non-equilibrium molecular dynamic simulations the flow of
      anomalous fluids inside rigid nanotubes. Our results reveal an anomalous increase
      of the overall mass flux for nanotubes with sufficiently smaller radii. This is
      explained in terms of a transition from a single-file type of flow to the
      movement of an ordered-like fluid as the nanotube radius increases. The
      occurrence of a global minimum in the mass flux at this transition reflects the
      competition between the two characteristic length scales of the core-softened
      potential. Moreover, by increasing further the radius, another substantial change
      in the flow behavior, which becomes more evident at low temperatures, leads to a
      local minimum in the overall mass flux. Microscopically, this second transition
      is originated by the formation of a double-layer of flowing particles in the
      confined nanotube space. These nano-fluidic features give insights about the
      behavior of confined isotropic anomalous fluids. 

PMID- 24852548
TI  - Spontaneous chiral resolution in two-dimensional systems of patchy particles.
AB  - Short ranged potentials and their anisotropy produce spontaneous chiral
      resolution in a two dimensional model of patchy particles introduced in this
      paper. This model could represent an equimolar binary mixture (racemic mixture)
      of two kinds of chiral molecules (enantiomers) adsorbed to a bi-dimensional
      domain where only lateral short ranged interactions are present. Most racemic
      mixtures undergo chiral resolution due to their spatial anisotropy, the combined
      effect of long range forces and the thermodynamic conditions. The patchy
      particles are modeled as a hard disk and four different bonding sites located to
      produce chirality. Phase behavior and structural properties are analysed using
      Discontinuous Molecular Dynamics in the canonical ensemble. When the four patchy
      particles are separated by the angles {60 degrees , 120 degrees , 60 degrees ,
      120 degrees }, spontaneous chiral resolution is produced, given by the formation
      of homochiral clusters, if started from the corresponding racemic mixture. Gel
      behavior is also obtained in all the systems for low temperatures and low
      densities. 

PMID- 24852549
TI  - Elastically cooperative activated barrier hopping theory of relaxation in viscous
      fluids. I. General formulation and application to hard sphere fluids.
AB  - We generalize the force-level nonlinear Langevin equation theory of single
      particle hopping to include collective effects associated with long range elastic
      distortion of the liquid. The activated alpha relaxation event is of a mixed
      spatial character, involving two distinct, but inter-related, local and
      collective barriers. There are no divergences at volume fractions below jamming
      or temperatures above zero Kelvin. The ideas are first developed and implemented
      analytically and numerically in the context of hard sphere fluids. In an
      intermediate volume fraction crossover regime, the local cage process is dominant
      in a manner consistent with an apparent Arrhenius behavior. The super-Arrhenius
      collective barrier is more strongly dependent on volume fraction, dominates the
      highly viscous regime, and is well described by a nonsingular law below jamming.
      The increase of the collective barrier is determined by the amplitude of thermal
      density fluctuations, dynamic shear modulus or transient localization length, and
      a growing microscopic jump length. Alpha relaxation time calculations are in good
      agreement with recent experiments and simulations on dense fluids and suspensions
      of hard spheres. Comparisons of the theory with elastic models and entropy crisis
      ideas are explored. The present work provides a foundation for constructing a
      quasi-universal, fit-parameter-free theory for relaxation in thermal molecular
      liquids over 14 orders of magnitude in time. 

PMID- 24852550
TI  - Elastically cooperative activated barrier hopping theory of relaxation in viscous
      fluids. II. Thermal liquids.
AB  - Building on the elastically collective nonlinear Langevin equation theory
      developed for hard spheres in Paper I, we propose and implement a quasi-universal
      theory for the alpha relaxation of thermal liquids based on mapping them to an
      effective hard sphere fluid via the dimensionless compressibility. The result is
      a zero adjustable parameter theory that can quantitatively address in a unified
      manner the alpha relaxation time over 14 or more decades. The theory has no
      singularities above zero Kelvin, and relaxation in the equilibrium low
      temperature limit is predicted to be of a roughly Arrhenius form. The two-barrier
      (local cage and long range collective elastic) description results in a rich
      dynamic behavior including apparent Arrhenius, narrow crossover, and deeply
      supercooled regimes, and multiple characteristic or crossover times and
      temperatures of clear physical meaning. Application of the theory to nonpolar
      molecules, alcohols, rare gases, and liquids metals is carried out. Overall, the
      agreement with experiment is quite good for the temperature dependence of the
      alpha time, plateau shear modulus, and Boson-like peak frequency for van der
      Waals liquids, though less so for hydrogen-bonding molecules. The theory predicts
      multiple growing length scales upon cooling, which reflect distinct aspects of
      the coupled local hopping and cooperative elastic physics. Calculations of the
      growth with cooling of an activation volume, which is strongly correlated with a
      measure of dynamic cooperativity, agree quantitatively with experiment.
      Comparisons with elastic, entropy crisis, dynamic facilitation, and other
      approaches are performed, and a fundamental basis for empirically extracted
      crossover temperatures is established. The present work sets the stage for
      addressing distinctive glassy phenomena in polymer melts, and diverse liquids
      under strong confinement. 

PMID- 24852551
TI  - Defect interactions with stepped CeO2/SrTiO3 interfaces: implications for
      radiation damage evolution and fast ion conduction.
AB  - Due to reduced dimensions and increased interfacial content, nanocomposite oxides
      offer improved functionalities in a wide variety of advanced technological
      applications, including their potential use as radiation tolerant materials. To
      better understand the role of interface structures in influencing the radiation
      damage tolerance of oxides, we have conducted atomistic calculations to elucidate
      the behavior of radiation-induced point defects (vacancies and interstitials) at
      interface steps in a model CeO2/SrTiO3 system. We find that atomic-scale steps at
      the interface have substantial influence on the defect behavior, which ultimately
      dictate the material performance in hostile irradiation environments. Distinctive
      steps react dissimilarly to cation and anion defects, effectively becoming biased
      sinks for different types of defects. Steps also attract cation interstitials,
      leaving behind an excess of immobile vacancies. Further, defects introduce
      significant structural and chemical distortions primarily at the steps. These two
      factors are plausible origins for the enhanced amorphization at steps seen in our
      recent experiments. The present work indicates that comprehensive examination of
      the interaction of radiation-induced point defects with the atomic-scale topology
      and defect structure of heterointerfaces is essential to evaluate the radiation
      tolerance of nanocomposites. Finally, our results have implications for other
      applications, such as fast ion conduction. 

PMID- 24852552
TI  - Determination of the thermodynamic correction factor of fluids confined in nano
      metric slit pores from molecular simulation.
AB  - The multi-component diffusive mass transport is generally quantified by means of
      the Maxwell-Stefan diffusion coefficients when using molecular simulations. These
      coefficients can be related to the Fick diffusion coefficients using the
      thermodynamic correction factor matrix, which requires to run several simulations
      to estimate all the elements of the matrix. In a recent work, Schnell et al.
      ["Thermodynamics of small systems embedded in a reservoir: A detailed analysis of
      finite size effects," Mol. Phys. 110, 1069-1079 (2012)] developed an approach to
      determine the full matrix of thermodynamic factors from a single simulation in
      bulk. This approach relies on finite size effects of small systems on the density
      fluctuations. We present here an extension of their work for inhomogeneous
      Lennard Jones fluids confined in slit pores. We first verified this extension by
      cross validating the results obtained from this approach with the results
      obtained from the simulated adsorption isotherms, which allows to determine the
      thermodynamic factor in porous medium. We then studied the effects of the pore
      width (from 1 to 15 molecular sizes), of the solid-fluid interaction potential
      (Lennard Jones 9-3, hard wall potential) and of the reduced fluid density (from
      0.1 to 0.7 at a reduced temperature T* = 2) on the thermodynamic factor. The
      deviation of the thermodynamic factor compared to its equivalent bulk value
      decreases when increasing the pore width and becomes insignificant for reduced
      pore width above 15. We also found that the thermodynamic factor is sensitive to
      the magnitude of the fluid-fluid and solid-fluid interactions, which softens or
      exacerbates the density fluctuations. 

PMID- 24852553
TI  - Phase diagram of the CF4 monolayer and bilayer on graphite.
AB  - We report an experimental study of physisorbed monolayers and bilayers of CF4 on
      graphite using infrared reflection absorption spectroscopy supplemented by
      ellipsometry. The symmetric C-F stretch mode nu3 near 1283 cm(-1) in the gas is
      strongly blue shifted in the film by dynamic dipole coupling. This blue shift
      provides a very sensitive measure of the inter-molecular spacing in the monolayer
      and, less directly, in the bilayer. We find that important corrections are
      necessary to the volumetric coverage scales used in previous heat capacity and x
      ray diffraction studies of this system. This requires quantitative and some
      qualitative changes to the previously proposed phase diagram. We find evidence
      for a new phase transition in the middle of the hexagonal incommensurate region
      and construct new phase diagrams in both the variables coverage-temperature and
      chemical potential-temperature. We determine the compressibility and thermal
      expansion in the low-pressure hexagonal incommensurate phase and values for the
      entropy change in several phase transitions. Below about 55 K there is evidence
      of solution of up to 7% of an impurity, most likely CO, in our monolayer but not
      the bilayer film. 

PMID- 24852554
TI  - Statistical mechanical models for dissociative adsorption of O2 on metal(100)
      surfaces with blocking, steering, and funneling.
AB  - We develop statistical mechanical models amenable to analytic treatment for the
      dissociative adsorption of O2 at hollow sites on fcc(100) metal surfaces. The
      models incorporate exclusion of nearest-neighbor pairs of adsorbed O. However,
      corresponding simple site-blocking models, where adsorption requires a large
      ensemble of available sites, exhibit an anomalously fast initial decrease in
      sticking. Thus, in addition to blocking, our models also incorporate more facile
      adsorption via orientational steering and funneling dynamics (features supported
      by ab initio Molecular Dynamics studies). Behavior for equilibrated adlayers is
      distinct from those with finite adspecies mobility. We focus on the low
      temperature limited-mobility regime where analysis of the associated master
      equations readily produces exact results for both short- and long-time behavior.
      Kinetic Monte Carlo simulation is also utilized to provide a more complete
      picture of behavior. These models capture both the initial decrease and the
      saturation of the experimentally observed sticking versus coverage, as well as
      features of non-equilibrium adlayer ordering as assessed by surface-sensitive
      diffraction. 

PMID- 24852555
TI  - Dissociation pathways of a single dimethyl disulfide on Cu(111): reaction induced
      by simultaneous excitation of two vibrational modes.
AB  - We present a novel reaction mechanism for a single adsorbed molecule that
      proceeds via simultaneous excitation of two different vibrational modes excited
      by inelastic tunneling electrons from a scanning tunneling microscope.
      Specifically, we analyze the dissociation of a single dimethyl disulfide (DMDS,
      (CH3S)2) molecule on Cu(111) by using a versatile theoretical method, which
      permits us to simulate reaction rates as a function of sample bias voltage. The
      reaction is induced by the excitation of C-H stretch and S-S stretch modes by a
      two-electron process at low positive bias voltages. However, at increased
      voltages, the dissociation becomes a single-electron process that excites a
      combination mode of these stretches, where excitation of the C-H stretch is the
      energy source and excitation of the S-S stretch mode enhances the anharmonic
      coupling rate. A much smaller dissociation yield (few orders of magnitude) at
      negative bias voltages is understood in terms of the projected density of states
      of a single DMDS on Cu(111), which reflects resonant excitation through the
      molecular orbitals. 

PMID- 24852556
TI  - Vapor liquid solid-hydride vapor phase epitaxy (VLS-HVPE) growth of ultra-long
      defect-free GaAs nanowires: ab initio simulations supporting center nucleation.
AB  - High aspect ratio, rod-like and single crystal phase GaAs nanowires (NWs) were
      grown by gold catalyst-assisted hydride vapor phase epitaxy (HVPE). High
      resolution transmission electron microscopy and micro-Raman spectroscopy revealed
      polytypism-free zinc blende (ZB) NWs over lengths of several tens of micrometers
      for a mean diameter of 50 nm. Micro-photoluminescence studies of individual NWs
      showed linewidths smaller than those reported elsewhere which is consistent with
      the crystalline quality of the NWs. HVPE makes use of chloride growth precursors
      GaCl of which high decomposition frequency after adsorption onto the liquid
      droplet catalysts, favors a direct and rapid introduction of the Ga atoms from
      the vapor phase into the droplets. High influxes of Ga and As species then yield
      high axial growth rate of more than 100 MUm/h. The diffusion of the Ga atoms in
      the liquid droplet towards the interface between the liquid and the solid
      nanowire was investigated by using density functional theory calculations. The
      diffusion coefficient of Ga atoms was estimated to be 3 * 10(-9) m(2)/s. The fast
      diffusion of Ga in the droplet favors nucleation at the liquid-solid line
      interface at the center of the NW. This is further evidence, provided by an
      alternative epitaxial method with respect to metal-organic vapor phase epitaxy
      and molecular beam epitaxy, of the current assumption which states that this type
      of nucleation should always lead to the formation of the ZB cubic phase. 

PMID- 24852557
TI  - Concentration fluctuations in miscible polymer blends: influence of temperature
      and chain rigidity.
AB  - In contrast to binary mixtures of small molecule fluids, homogeneous polymer
      blends exhibit relatively large concentration fluctuations that can strongly
      affect the transport properties of these complex fluids over wide ranges of
      temperatures and compositions. The spatial scale and intensity of these
      compositional fluctuations are studied by applying Kirkwood-Buff theory to model
      blends of linear semiflexible polymer chains with upper critical solution
      temperatures. The requisite quantities for determining the Kirkwood-Buff
      integrals are generated from the lattice cluster theory for the thermodynamics of
      the blend and from the generalization of the random phase approximation to
      compressible polymer mixtures. We explore how the scale and intensity of
      composition fluctuations in binary blends vary with the reduced temperature tau =
      (T - T(c))/T (where T(c) is the critical temperature) and with the asymmetry in
      the rigidities of the components. Knowledge of these variations is crucial for
      understanding the dynamics of materials fabricated from polymer blends, and
      evidence supporting these expectations is briefly discussed.

PMID- 24852558
TI  - Structural and phase transitions of one and two polymer mushrooms in poor
      solvent.
AB  - Using the recently proposed fast lattice Monte Carlo (FLMC) simulations and the
      corresponding lattice self-consistent field (LSCF) calculations based on the same
      model system, where multiple occupancy of lattice sites is allowed [Q. Wang, Soft
      Matter 5, 4564 (2009); Q. Wang, Soft Matter 5, 6206 (2010)], we studied the coil
      globule transition (CGT) of one-mushroom systems and the fused-separated
      transition (FST) of two-mushroom systems, where a polymer mushroom is formed by a
      group of n homopolymer chains each of N segments end-grafted at the same point
      onto a flat substrate and immersed in a poor solvent. With our soft potential
      that allows complete particle overlapping, LSCF theory neglecting the system
      fluctuations/correlations becomes exact in the limit of n -> infinity, and FLMC
      results approach LSCF predictions with increasing n. Using LSCF calculations, we
      systematically constructed the phase diagrams of one- and two-mushroom systems. A
      second-order symmetric-asymmetric transition (SAT) was found in the globule state
      of one-mushroom systems, where the rotational symmetry around the substrate
      normal passing through the grafting point is broken in each individual
      configuration but preserved by the degeneracy of different orientations of these
      asymmetric configurations. Three different states were also found in two-mushroom
      systems: separated coils, separated globules, and fused globule. We further
      studied the coupling between FST in two-mushroom systems and CGT and SAT of each
      mushroom. Finally, direct comparisons between our simulation and theoretical
      results, without any parameter-fitting, unambiguously and quantitatively revealed
      the fluctuation/correlation effects on these phase transitions. 

PMID- 24852559
TI  - Exact evaluation of the depletion force between nanospheres in a polydisperse
      polymer fluid under Theta conditions.
AB  - We analyze a system consisting of two spherical particles immersed in a
      polydispersed polymer solution under theta conditions. An exact theory is
      developed to describe the potential of mean force between the spheres for the
      case where the polymer molecular weight dispersity is described by the Schulz
      Flory distribution. Exact results can be derived for the protein regime, where
      the sphere radius (R(s)) is small compared to the average radius of gyration of
      the polymer (R(g)). Numerical results are relatively easily obtained in the cases
      where the sphere radius is increased. We find that even when q = R(g)/R(s) ? 10,
      then the use of a monopole expansion for the polymer end-point distribution about
      the spheres is sufficient. For even larger spheres q ~ 1, accuracy is maintained
      by including a dipolar correction. The implications of these findings on
      generating a full many-body effective interaction for a collection of N spheres
      imbedded in the polymer solution are discussed.

PMID- 24852561
TI  - Conformation of polyelectrolytes in poor solvents: variational approach and
      quantitative comparison with scaling predictions.
AB  - We present the results of variational calculations of a polyelectrolyte solution
      with low salt in poor solvent conditions for a polymer backbone. By employing the
      variation method, we quantitatively determined the diagram of the state of the
      polyelectrolyte in poor solvents as a function of the charge density and the
      molecular weight. The exact structure and diagram of the polyelectrolyte were
      compared to the scaling predictions of the necklace model developed by Dobrynin
      and Rubinstein [Prog. Polym. Sci. 30, 1049-1118 (2005); Dobrynin and Rubinstein,
      Macromolecules 32, 915-922 (1999); Dobrynin and Rubinstein, Macromolecules 34,
      1964-1972 (2001)]. We find that the scaling necklace model may be used as a
      rather good estimation and analytical approximation of the exact variational
      model. It is also pointed out that the molecular connection of polymer is crucial
      for ellipsoid and necklace conformation. 

PMID- 24852560
TI  - Coating thickness and coverage effects on the forces between silica nanoparticles
      in water.
AB  - The structure and interactions of coated silica nanoparticles have been studied
      in water using molecular dynamics simulations. For 5 nm diameter amorphous silica
      nanoparticles, we studied the effects of varying the chain length and grafting
      density of polyethylene oxide on the nanoparticle coating's shape and on
      nanoparticle-nanoparticle effective forces. For short ligands of length n = 6 and
      n = 20 repeat units, the coatings are radially symmetric while for longer chains
      (n = 100) the coatings are highly anisotropic. This anisotropy appears to be
      governed primarily by chain length, with coverage playing a secondary role. For
      the largest chain lengths considered, the strongly anisotropic shape makes
      fitting to a simple radial force model impossible. For shorter ligands, where the
      coatings are isotropic, we found that the force between pairs of nanoparticles is
      purely repulsive and can be fit to the form (R/2r(core) - 1)(-b) where R is the
      separation between the center of the nanoparticles, r(core) is the radius of the
      silica core, and b is measured to be between 2.3 and 4.1.

PMID- 24852562
TI  - Asymptotic solutions of the Oosawa model for the length distribution of
      biofilaments.
AB  - Nucleated polymerisation phenomena are general linear growth processes that
      underlie the formation of a range of biofilaments in nature, including actin and
      tubulin that are key components of the cellular cytoskeleton. The conventional
      theoretical framework for describing this process is the Oosawa model that takes
      into account homogeneous nucleation coupled to linear growth. In his original
      work, Oosawa provided an analytical solution to the total mass concentration of
      filaments; the time evolution of the full length distribution has, however, been
      challenging to access, in large part due to the nonlinear nature of the rate
      equations inherent in the description of such phenomena and to date analytical
      solutions for the filament distribution are known only in certain special cases.
      Here, by exploiting a technique based on the method of matched asymptotics, we
      present an analytical treatment of the Oosawa model that describes the shape of
      the length distribution of biofilaments reversibly growing through primary
      nucleation and filament elongation. Our work highlights the power of matched
      asymptotics for obtaining closed-form analytical solutions to nonlinear master
      equations in biophysics and allows us to identify the key time scales that
      characterize biological polymerization processes. 

PMID- 24852563
TI  - Iterative derivation of effective potentials to sample the conformational space
      of proteins at atomistic scale.
AB  - The current capacity of computers makes it possible to perform simulations of
      small systems with portable, explicit-solvent potentials achieving high degree of
      accuracy. However, simplified models must be employed to exploit the behavior of
      large systems or to perform systematic scans of smaller systems. While powerful
      algorithms are available to facilitate the sampling of the conformational space,
      successful applications of such models are hindered by the availability of simple
      enough potentials able to satisfactorily reproduce known properties of the
      system. We develop an interatomic potential to account for a number of properties
      of proteins in a computationally economic way. The potential is defined within an
      all-atom, implicit solvent model by contact functions between the different atom
      types. The associated numerical values can be optimized by an iterative Monte
      Carlo scheme on any available experimental data, provided that they are
      expressible as thermal averages of some conformational properties. We test this
      model on three different proteins, for which we also perform a scan of all
      possible point mutations with explicit conformational sampling. The resulting
      models, optimized solely on a subset of native distances, not only reproduce the
      native conformations within a few Angstroms from the experimental ones, but show
      the cooperative transition between native and denatured state and correctly
      predict the measured free-energy changes associated with point mutations.
      Moreover, differently from other structure-based models, our method leaves a
      residual degree of frustration, which is known to be present in protein
      molecules. 

PMID- 24852564
TI  - Sampling the equilibrium kinetic network of Trp-cage in explicit solvent.
AB  - We employed the single replica multiple state transition interface sampling
      (MSTIS) approach to sample the kinetic (un)folding network of Trp-cage mini
      protein in explicit water. Cluster analysis yielded 14 important metastable
      states in the network. The MSTIS simulation thus resulted in a full 14 * 14 rate
      matrix. Analysis of the kinetic rate matrix indicates the presence of a near
      native intermediate state characterized by a fully formed alpha helix, a slightly
      disordered proline tail, a broken salt-bridge, and a rotated arginine residue.
      This intermediate was also found in recent IR experiments. Moreover, the
      predicted rate constants and timescales are in agreement with previous
      experiments and simulations. 

PMID- 24852565
TI  - Flow time through esophagogastric junction derived during high-resolution
      impedance-manometry studies: a novel parameter for assessing esophageal bolus
      transit.
AB  - This study aimed to develop and validate a method to measure bolus flow time
      (BFT) through the esophagogastric junction (EGJ) using a high-resolution
      impedance-manometry (HRIM) sleeve. Ten healthy subjects were studied with
      concurrent HRIM and videofluoroscopy; another 15 controls were studied with HRIM
      alone. HRIM studies were performed using a 4.2-mm-outer diameter assembly with 36
      pressure sensors at 1-cm intervals and 18 impedance segments at 2-cm intervals
      (Given Imaging, Los Angeles, CA). HRIM and fluoroscopic data from four barium
      swallows, two in the supine and two in the upright position, were analyzed to
      create a customized MATLAB program to calculate BFT using a HRIM sleeve
      comprising three sensors positioned at the crural diaphragm. Bolus transit
      through the EGJ measured during blinded review of fluoroscopy was almost
      identical to BFT calculated with the HRIM sleeve, with the nadir impedance
      deflection point used as the signature of bolus presence. Good correlation
      existed between videofluoroscopy for measurement of upper sphincter relaxation to
      beginning of flow [R = 0.97, P < 0.001 (supine) and R = 0.77, P < 0.01 (upright)]
      and time to end of flow [R = 0.95, P < 0.001 (supine) and R = 0.82, P < 0.01
      (upright)]. The medians and interquartile ranges (IQR) of flow time though the
      EGJ in 15 healthy subjects calculated using the virtual sleeve were 3.5 s (IQR
      2.3-3.9 s) in the supine position and 3.2 s (IQR 2.3-3.6 s) in the upright
      position. BFT is a new metric that provides important information about bolus
      transit through the EGJ. An assessment of BFT will determine when the EGJ is open
      and will also provide a useful method to accurately assess trans-EGJ pressure
      gradients during flow. 

PMID- 24852567
TI  - Converging effects of a Bifidobacterium and Lactobacillus probiotic strain on
      mouse intestinal physiology.
AB  - Evidence has grown to support the efficacy of probiotics in the management of
      gastrointestinal disorders, many of which are associated with dysregulated fluid
      and electrolyte transport. A growing body of evidence now suggests that the host
      microbiota and probiotics can influence intestinal ion transport and that these
      effects often occur in a strain-dependent manner. In this study, we sought to
      investigate the effects of two therapeutically relevant organisms,
      Bifidobacterium infantis 35,624 and Lactobacillus salivarius UCC118, on small
      intestinal transit, fecal output and water content, transepithelial resistance
      (TER), and colonic secretomotor function. Mice fed either strain displayed
      significantly reduced small intestinal transit in vivo, though neither strain
      influenced fecal pellet output or water content. Colon from mice fed both
      organisms displayed increased colonic TER, without a concomitant change in the
      gene expression of the tight junction proteins claudin 1 and occludin. However,
      L. salivarius UCC118 selectively inhibited neurally evoked ion secretion in
      tissues from animals fed this particular probiotic. Consistent with this finding,
      the neurotoxin tetrodotoxin (TTx) significantly inhibited the short-circuit
      current response induced by L. salivarius UCC118 following addition to colonic
      preparations in Ussing chambers. Responses to B. infantis 35,624 also displayed
      sensitivity to TTx, although to a significantly lesser degree than L. salivarius
      UCC118. Both strains similarly inhibited cholinergic-induced ion transport after
      addition to Ussing chambers. Taken together, these data suggest that B. infantis
      35,624 and L. salivarius UCC118 may be indicated in disorders associated with
      increased small intestinal transit, and, in particular for L. salivarius UCC118,
      neurally mediated diarrhea.

PMID- 24852566
TI  - Lactobacillus reuteri DSM 17938 differentially modulates effector memory T cells
      and Foxp3+ regulatory T cells in a mouse model of necrotizing enterocolitis.
AB  - Necrotizing enterocolitis (NEC) is an inflammatory disease with evidence of
      increased production of proinflammatory cytokines in the intestinal mucosa.
      Lactobacillus reuteri DSM 17938 (LR17938) has been shown to have anti
      inflammatory activities in an experimental model of NEC. Activated effector
      lymphocyte recruitment to sites of inflammation requires the sequential
      engagement of adhesion molecules such as CD44. The phenotype of CD44(+)CD45RB(lo)
      separates T effector/memory (Tem) cells from naive (CD44(-)CD45RB(hi)) cells. It
      is unknown whether these Tem cells participate in the inflammation associated
      with NEC and can be altered by LR17938. NEC was induced in 8- to 10-day-old
      C57BL/6J mice by gavage feeding with formula and exposure to hypoxia and cold
      stress for 4 days. Survival curves and histological scores were analyzed.
      Lymphocytes isolated from mesenteric lymph nodes and ileum were labeled for CD4,
      CD44, CD45RB, intracellular Foxp3, and Helios and subsequently analyzed by flow
      cytometry. LR17938 decreased mortality and the incidence and severity of NEC. The
      percentage of Tem cells in the ileum and mesenteric lymph nodes was increased in
      NEC but decreased by LR17938. Conversely, the percentage of CD4(+)Foxp3(+)
      regulatory T (Treg) cells in the intestine decreased during NEC and was restored
      to normal by LR17938. The majority of the Treg cells preserved by LR17938 were
      Helios+ subsets, possibly of thymic origin. In conclusion, LR17938 may represent
      a useful treatment to prevent NEC. The mechanism of protection by LR17938
      involves modulation of the balance between Tem and Treg cells. These T cell
      subsets might be potential biomarkers and therapeutic targets during intestinal
      inflammation.

PMID- 24852571
TI  - Personalized medicine, availability, and group disparity: an inquiry into how
      physicians perceive and rate the elements and barriers of personalized medicine.
AB  - BACKGROUND: The success of personalized medicine depends on factors influencing
      the availability and implementation of its new tools to individualize clinical
      care. However, little is known about physicians' views of the availability of
      personalized medicine across racial/ethnic groups and the relationship between
      perceived availability and clinical implementation. This study examines
      physicians' perceptions of key elements/tools and potential barriers to
      personalized medicine in connection with their perceptions of the availability of
      the latter across subpopulations. METHODS: Study subjects consisted of physicians
      recruited from Cincinnati Children's Hospital Medical Center and UC Health. An
      electronic survey conducted from September 2012 to November 2012 recruited 104
      physicians. Wilcoxon rank sum analysis compared groups. RESULTS: Physicians were
      divided about whether personalized medicine contributes to health equality, as
      37.4% of them believe that personalized medicine is currently available only for
      some subpopulations. They also rated the importance of racial/ethnic background
      almost as high as the importance of genetic information in the delivery of
      personalized medicine. Actual elements of personalized medicine rated highest
      include family history, drug-drug interaction alerts in medical records, and
      biomarker measurements to guide therapy. Costs of gene-based therapies and
      genetic testing were rated the most significant barriers. The ratings of several
      elements and barriers were associated with perceived availability of personalized
      medicine across subpopulations. CONCLUSION: While physicians hold differing views
      about the availability and implementation of personalized medicine, they likewise
      establish complex relationships between race/ethnicity and personalized medicine
      that may carry serious implications for its clinical success.

PMID- 24852572
TI  - An evaluation of Hospice New Zealand's interprofessional fundamentals of
      palliative care program at a single site.
AB  - OBJECTIVE: To study the efficacy of two modules within the Fundamentals of
      Palliative Care educational program within a single site. The modules included
      the concepts of Essence of Palliative Care and Pain and Symptom Management.
      METHOD: A mixed-methods approach incorporating questionnaires and interviews was
      implemented. Two phases were included. First, a purposive sample of 22 workshop
      participants were invited to fill out evaluation questionnaires on two occasions
      (immediately after the session and four weeks as follow-up). Second,
      semistructured interviews were conducted and interviews transcribed and analyzed
      using content analysis. RESULTS: Participants felt they gained further knowledge
      in palliative patient management and refined their clinical practice. The
      questionnaire feedback revealed that the Essence of Palliative Care module
      provided a breadth of content but had difficulties in capturing the diverse needs
      of all attendees. The Pain and Symptom Management module was perceived as more
      technical and clinical, and this suited health professionals with an informed
      background. The interviewee feedback (three nurses, three nurse educators, one
      manager) suggested that the learning outcomes were comprehensive but needed to be
      more sensitive to learner needs. The teaching and learning activities were
      perceived as useful and encouraging. However, learners came from diverse
      contexts, and it was difficult to suit all learning preferences. Assessment and
      evaluation processes required more psychometric attention. SIGNIFICANCE OF
      RESULTS: The piloting of the Fundamentals of Palliative Care program at this
      single site was of benefit and relevance to participants in their clinical
      practice. Overall, participants felt the course was useful to them and that they
      were able to gain valuable knowledge and skills. Several areas could be refined
      to optimize the learning, including: (1) knowing attendee learning potentialities
      and prior experiences, (2) considering a more inclusive and formal assessment
      process, (3) creating diverse mechanisms for disseminating knowledge and skills,
      and (4) improving methods of evaluation.

PMID- 24852568
TI  - H1-antihistamines exacerbate high-fat diet-induced hepatic steatosis in wild-type
      but not in apolipoprotein E knockout mice.
AB  - We examined the effects of two over-the-counter H1-antihistamines on the
      progression of fatty liver disease in male C57Bl/6 wild-type and apolipoprotein E
      (ApoE)-/- mice. Mice were fed a high-fat diet (HFD) for 3 mo, together with
      administration of either cetirizine (4 mg/kg body wt) or fexofenadine (40 mg/kg
      body wt) in drinking water. Antihistamine treatments increased body weight gain,
      gonadal fat deposition, liver weight, and hepatic steatosis in wild-type mice but
      not in ApoE-/- mice. Lobular inflammation, acute inflammation, and necrosis were
      not affected by H1-antihistamines in either genotype. Serum biomarkers of liver
      injury tended to increase in antihistamine-treated wild-type mice. Serum level of
      glucose was increased by fexofenadine, whereas lipase was increased by
      cetirizine. H1-antihistamines reduced the mRNA expression of ApoE and
      carbohydrate response element-binding protein in wild-type mice, without altering
      the mRNA expression of sterol regulatory element-binding protein 1c, fatty acid
      synthase, or ApoB100, in either genotype. Fexofenadine increased both
      triglycerides and cholesterol ester, whereas cetirizine increased only
      cholesterol ester in liver, with a concomitant decrease in serum triglycerides by
      both antihistamines in wild-type mice. Antihistamines increased hepatic levels of
      conjugated bile acids in wild-type mice, with the effect being significant in
      fexofenadine-treated animals. The increase was associated with changes in the
      expression of organic anion transport polypeptide 1b2 and bile salt export pump.
      These results suggest that H1-antihistamines increase the progression of fatty
      liver disease in wild-type mice, and there seems to be an association between the
      severity of disease, presence of ApoE, and increase in hepatic bile acid levels. 

PMID- 24852569
TI  - In Barrett's esophagus patients and Barrett's cell lines, ursodeoxycholic acid
      increases antioxidant expression and prevents DNA damage by bile acids.
AB  - Hydrophobic bile acids like deoxycholic acid (DCA), which cause oxidative DNA
      damage and activate NF-kappaB in Barrett's metaplasia, might contribute to
      carcinogenesis in Barrett's esophagus. We have explored mechanisms whereby
      ursodeoxycholic acid (UDCA, a hydrophilic bile acid) protects against DCA-induced
      injury in vivo in patients and in vitro using nonneoplastic, telomerase
      immortalized Barrett's cell lines. We took biopsies of Barrett's esophagus from
      21 patients before and after esophageal perfusion with DCA (250 MUM) at baseline
      and after 8 wk of oral UDCA treatment. DNA damage was assessed by phospho-H2AX
      expression, neutral CometAssay, and phospho-H2AX nuclear foci formation.
      Quantitative PCR was performed for antioxidants including catalase and GPX1.
      Nrf2, catalase, and GPX1 were knocked down with siRNAs. Reporter assays were
      performed using a plasmid construct containing antioxidant responsive element. In
      patients, baseline esophageal perfusion with DCA significantly increased phospho
      H2AX and phospho-p65 in Barrett's metaplasia. Oral UDCA increased GPX1 and
      catalase levels in Barrett's metaplasia and prevented DCA perfusion from inducing
      DNA damage and NF-kappaB activation. In cells, DCA-induced DNA damage and NF
      kappaB activation was prevented by 24-h pretreatment with UDCA, but not by mixing
      UDCA with DCA. UDCA activated Nrf2 signaling to increase GPX1 and catalase
      expression, and protective effects of UDCA pretreatment were blocked by siRNA
      knockdown of these antioxidants. UDCA increases expression of antioxidants that
      prevent toxic bile acids from causing DNA damage and NF-kappaB activation in
      Barrett's metaplasia. Elucidation of this molecular pathway for UDCA protection
      provides rationale for clinical trials on UDCA for chemoprevention in Barrett's
      esophagus. 

PMID- 24852570
TI  - Sex-related differences in growth and carbon allocation to defence in Populus
      tremula as explained by current plant defence theories.
AB  - Plant defence theories have recently evolved in such a way that not only the
      quantity but also the quality of mineral nutrients is expected to influence plant
      constitutive defence. Recently, an extended prediction derived from the protein
      competition model (PCM) suggested that nitrogen (N) limitation is more important
      for the production of phenolic compounds than phosphorus (P). We aimed at
      studying sexual differences in the patterns of carbon allocation to growth and
      constitutive defence in relation to N and P availability in Populus tremula L.
      seedlings. We compared the gender responses in photosynthesis, growth and whole
      plant allocation to phenolic compounds at different combination levels of N and
      P, and studied how they are explained by the main plant defence theories. We
      found no sexual differences in phenolic concentrations, but interestingly, slow
      growing females had higher leaf N concentration than did males, and genders
      differed in their allocation priority. There was a trade-off between growth and
      the production of flavonoid-derived phenylpropanoids on one hand, and between the
      production of salicylates and flavonoid-derived phenylpropanoids on the other.
      Under limited nutrient conditions, females prioritized mineral nutrient
      acquisition, flavonoid and condensed tannin (CT) production, while males invested
      more in above-ground biomass. Salicylate accumulation followed the growth
      differentiation balance hypothesis as low N mainly decreased the production of
      leaf and stem salicylate content while the combination of both low N and low P
      increased the amount of flavonoids and CTs allocated to leaves and to a lesser
      extent stems, which agrees with the PCM. We suggest that such a discrepancy in
      the responses of salicylates and flavonoid-derived CTs is linked to their clearly
      distinct biosynthetic origins and/or their metabolic costs.

PMID- 24852573
TI  - Metagenomic analyses reveal the involvement of syntrophic consortia in
      methanol/electricity conversion in microbial fuel cells.
AB  - Methanol is widely used in industrial processes, and as such, is discharged in
      large quantities in wastewater. Microbial fuel cells (MFCs) have the potential to
      recover electric energy from organic pollutants in wastewater; however, the use
      of MFCs to generate electricity from methanol has not been reported. In the
      present study, we developed single-chamber MFCs that generated electricity from
      methanol at the maximum power density of 220 mW m(-2) (based on the projected
      area of the anode). In order to reveal how microbes generate electricity from
      methanol, pyrosequencing of 16S rRNA-gene amplicons and Illumina shotgun
      sequencing of metagenome were conducted. The pyrosequencing detected in abundance
      Dysgonomonas, Sporomusa, and Desulfovibrio in the electrolyte and anode and
      cathode biofilms, while Geobacter was detected only in the anode biofilm. Based
      on known physiological properties of these bacteria, it is considered that
      Sporomusa converts methanol into acetate, which is then utilized by Geobacter to
      generate electricity. This speculation is supported by results of shotgun
      metagenomics of the anode-biofilm microbes, which reconstructed relevant
      catabolic pathways in these bacteria. These results suggest that methanol is
      anaerobically catabolized by syntrophic bacterial consortia with electrodes as
      electron acceptors.

PMID- 24852574
TI  - Symptoms of nicotine toxicity in subjects achieving high cotinine levels during
      nicotine replacement therapy.
AB  - INTRODUCTION: Nicotine replacement therapy (NRT) aids smoking reduction and
      cessation. Although NRT is effective and safe, some smokers may achieve high
      nicotine levels. The purpose of this study was to determine the incidence and
      severity of nicotine-related adverse events in subjects with levels of cotinine,
      a metabolite of nicotine, that increased by >50% compared with baseline smoking
      in controlled clinical trials of NRT. METHODS: Data from participants in
      randomized, double-blind, controlled trials of various formulations of NRT
      (Nicorette(r)), including patch, gum, oral inhaler, sublingual tablet, nasal
      spray, mouth spray, and combinations, were extracted from a clinical database.
      Eligible studies were performed between 1989 and 2010. In addition to baseline,
      at least 1 subsequent plasma or salivary cotinine concentration was measured, and
      adverse events were recorded simultaneously. Of 28 eligible studies, 24 were
      smoking cessation studies and 4 were smoking reduction studies. RESULTS: Cotinine
      levels that increased by >50% above baseline were recorded during treatment in
      746 of 7,120 subjects (10.5%). Nausea was reported in 16 subjects (0.2% of the
      total, upper 99% confidence limit [CL] 0.4%), vomiting in 2 subjects (0.0%, upper
      99% CL 0.1%), palpitations in 5 subjects (0.1%, upper 99% CL 0.2%), dizziness in
      11 subjects (0.2%; upper 99% CL 0.3%), and headache in 35 subjects (0.5%, upper
      99% CL 0.7%). CONCLUSIONS: Typical symptoms indicating nicotine overdose together
      with high cotinine levels were rare during treatment with NRT. These findings
      support the safety of NRT for smoking cessation or reduction.

PMID- 24852576
TI  - Effects of lipid environment on the conformational changes of an ABC importer.
AB  - In order to shuttle substrates across the lipid bilayer, membrane proteins
      undergo a series of conformation changes that are influenced by protein
      structure, ligands, and the lipid environment. To test the effect of lipid on
      conformation change of the ABC transporter MolBC, EPR studies were conducted in
      lipids and detergents of variable composition. In both a detergent and lipid
      environment, MolBC underwent the same general conformation changes as detected by
      site-directed EPR spectroscopy. However, differences in activity and the details
      of the EPR analysis indicate conformational rigidity that is dependent on the
      lipid environment. From these observations, we conclude that native-like lipid
      mixtures provide the transporter with greater activity and conformational
      flexibility as well as technical advantages such as reconstitution efficiency and
      protein stability.

PMID- 24852575
TI  - Methylmercury alters the activities of Hsp90 client proteins, prostaglandin E
      synthase/p23 (PGES/23) and nNOS.
AB  - Methylmercury (MeHg) is a persistent pollutant with known neurotoxic effects. We
      have previously shown that astrocytes accumulate MeHg and play a prominent role
      in mediating MeHg toxicity in the central nervous system (CNS) by altering
      glutamate signaling, generating oxidative stress, depleting glutathione (GSH) and
      initiating lipid peroxidation. Interestingly, all of these pathways can be
      regulated by the constitutively expressed, 90-kDa heat shock protein, Hsp90. As
      Hsp90 function is regulated by oxidative stress, we hypothesized that MeHg
      disrupts Hsp90-client protein functions. Astrocytes were treated with MeHg and
      expression of Hsp90, as well as the abundance of complexes of Hsp90-neuronal
      nitric oxide synthase (nNOS) and Hsp90-prostaglandin E synthase/p23 (PGES/p23)
      were assessed. MeHg exposure decreased Hsp90 protein expression following 12 h of
      treatment while shorter exposures had no effect on Hsp90 protein expression.
      Interestingly, following 1 or 6 h of MeHg exposure, Hsp90 binding to PGES/p23 or
      nNOS was significantly increased, resulting in increased prostaglandin E2 (PGE2)
      synthesis from MeHg-treated astrocytes. These effects were attenuated by the
      Hsp90 antagonist, geldanmycin. NOS activity was increased following MeHg
      treatment while cGMP formation was decreased. This was accompanied by an increase
      in *O2- and H2O2 levels, suggesting that MeHg uncouples NO formation from NO
      dependent signaling and increases oxidative stress. Altogether, our data
      demonstrates that Hsp90 interactions with client proteins are increased following
      MeHg exposure, but over time Hsp90 levels decline, contributing to oxidative
      stress and MeHg-dependent excitotoxicity. 

PMID- 24852578
TI  - How safe is safe enough?

PMID- 24852580
TI  - A tale of two emergency visits.

PMID- 24852577
TI  - Pharmacological identification of a guanidine-containing beta-alanine analogue
      with low micromolar potency and selectivity for the betaine/GABA transporter 1
      (BGT1).
AB  - The gamma-aminobutyric acid (GABA) transporters (GATs) are key membrane
      transporter proteins involved in the termination of GABAergic signaling at
      synapses in the mammalian brain and proposed drug targets in neurological
      disorders such as epilepsy. To date, four different GAT subtypes have been
      identified: GAT1, GAT2, GAT3 and the betaine/GABA transporter 1 (BGT1). Owing to
      the lack of potent and subtype selective inhibitors of the non-GAT1 GABA
      transporters, the physiological role and therapeutic potential of these
      transporters remain to be fully understood. Based on bioisosteric replacement of
      the amino group in beta-alanine or GABA, a series of compounds was generated, and
      their pharmacological activity assessed at human GAT subtypes. Using a cell-based
      [(3)H]GABA uptake assay, several selective inhibitors at human BGT1 were
      identified. The guanidine-containing compound 9 (2-amino-1,4,5,6
      tetrahydropyrimidine-5-carboxylic acid hydrochloride) displayed more than 250
      times greater potency than the parent compound beta-alanine at BGT1 and is thus
      the most potent inhibitor reported to date for this subtype (IC50 value of 2.5
      uM). In addition, compound 9 displayed about 400, 16 and 40 times lower
      inhibitory potency at GAT1, GAT2 and GAT3, respectively. Compound 9 was shown to
      be a substrate for BGT1 and to have an overall similar pharmacological profile at
      the mouse orthologue. Compound 9 constitutes an interesting pharmacological tool
      for specifically investigating the cellular pharmacology of BGT1 and is the first
      small-molecule substrate identified with such a high selectivity for BGT1 over
      the three other GAT subtypes.

PMID- 24852581
TI  - Assessment of consultation impact on emergency department operations through
      novel metrics of responsiveness and decision-making efficiency.
AB  - OBJECTIVES: Requests for specialty consultation are common in emergency
      departments (EDs) and often contribute to delays in throughput. Our objectives
      were to describe the contribution of the consultation process to total ED length
      of stay (LOS) through novel metrics and illustrate causes of delay. METHODS: We
      conducted a prospective cross-sectional study at three Canadian tertiary care
      centres. Adult ED patients with requested medical/surgical consultations were
      enrolled. We created original metric intervals: total consultation time (TCT)
      defined as the interval from the initial consultation request to the disposition
      decision, consult response time (CRT) from the request to the consultant arrival,
      and decision-making interval (DMI) from arrival to the disposition decision. The
      consultation impact index (CII) was defined as the percentage of ED LOS consumed
      by the TCT. Reasons for delay were documented if time stamps exceeded preset
      benchmarks. RESULTS: The median TCT for 285 patients was 138 minutes
      (interquartile range [IQR]: 82-239 minutes), whereas the median total ED LOS was
      778 minutes (IQR 485-1,274 minutes). The median CRT was 55 minutes (IQR 21-115
      minutes), and the median DMI was 58 minutes (IQR 25-126 minutes). The CII
      measured 26% (95% CI 23-28). Major contributors to consultation delay included
      urgent ward issues, simultaneous ED consultations, and the need for additional
      laboratory or radiographic investigations. CONCLUSION: The consultation process
      is highly variable and has an important impact on ED LOS. We describe novel
      measures related to consultation performance and provide an analysis of what
      causes delays. These results can be used to seek improvements in the consulting
      process.

PMID- 24852582
TI  - Detection and correction of prescription errors by an emergency department
      pharmacy service.
AB  - OBJECTIVES: Emergency departments (EDs) are recognized as a high-risk setting for
      prescription errors. Pharmacist involvement may be important in reviewing
      prescriptions to identify and correct errors. The objectives of this study were
      to describe the frequency and type of prescription errors detected by pharmacists
      in EDs, determine the proportion of errors that could be corrected, and identify
      factors associated with prescription errors. METHODS: This prospective
      observational study was conducted in a tertiary care teaching ED on 25
      consecutive weekdays. Pharmacists reviewed all documented prescriptions and
      flagged and corrected errors for patients in the ED. We collected information on
      patient demographics, details on prescription errors, and the pharmacists'
      recommendations. RESULTS: A total of 3,136 ED prescriptions were reviewed. The
      proportion of prescriptions in which a pharmacist identified an error was 3.2%
      (99 of 3,136; 95% confidence interval [CI] 2.5-3.8). The types of identified
      errors were wrong dose (28 of 99, 28.3%), incomplete prescription (27 of 99,
      27.3%), wrong frequency (15 of 99, 15.2%), wrong drug (11 of 99, 11.1%), wrong
      route (1 of 99, 1.0%), and other (17 of 99, 17.2%). The pharmacy service
      intervened and corrected 78 (78 of 99, 78.8%) errors. Factors associated with
      prescription errors were patient age over 65 (odds ratio [OR] 2.34; 95% CI 1.32
      4.13), prescriptions with more than one medication (OR 5.03; 95% CI 2.54-9.96),
      and those written by emergency medicine residents compared to attending emergency
      physicians (OR 2.21, 95% CI 1.18-4.14). CONCLUSIONS: Pharmacists in a tertiary ED
      are able to correct the majority of prescriptions in which they find errors.
      Errors are more likely to be identified in prescriptions written for older
      patients, those containing multiple medication orders, and those prescribed by
      emergency residents.

PMID- 24852583
TI  - An inventory of Canadian trauma systems: opportunities for improving access to
      trauma care.
AB  - OBJECTIVE: Despite evidence that patients suffering major traumatic injuries have
      improved outcomes when cared for within an organized system, the extent of trauma
      system development in Canada is limited. We sought to compile a detailed
      inventory of trauma systems in Canada as a first step toward identifying
      opportunities for improving access to trauma care. METHODS: We distributed a
      nationwide online and mail survey to stakeholders intended to evaluate the extent
      of implementation of specific trauma system components. Targeted stakeholders
      included emergency physicians, trauma surgeons, trauma program medical directors
      and program managers, prehospital providers, and decision makers at the regional
      and provincial levels. A "snowball" approach was used to expand the sample base
      of the survey. Descriptive statistics were generated to quantify the nature and
      extent of trauma system development by region. RESULTS: The overall response rate
      was 38.7%, and all levels of stakeholders and all provinces/territories were
      represented. All provinces were found to have designated trauma centres; however,
      only 60% were found to have been accredited within the past 10 years. Components
      present in 50% or fewer provinces included an inclusive trauma system model,
      interfacility transfer agreements, and a mechanism to track bed availability
      within the system. CONCLUSION: There is significant variability in the extent of
      trauma system development in Canada. Although all provinces have designated
      trauma centres, opportunities exist in many systems to implement additional
      components to improve the inclusiveness of care. In future work, we intend to
      quantify the strength of the relationship between different trauma system
      components and access to definitive trauma care.

PMID- 24852584
TI  - A randomized, controlled trial of oral versus intravenous fluids for lowering
      blood glucose in emergency department patients with hyperglycemia.
AB  - OBJECTIVES: Blood glucose can be lowered via insulin and/or fluid administration.
      Insulin, although efficacious, can cause hypoglycemia and hypokalemia. Fluids do
      not cause hypoglycemia or hypokalemia, but the most effective route of fluid
      administration has not been well described. This study compared the efficacy and
      safety of oral versus intravenous fluids for reducing blood glucose in patients
      with hyperglycemia. METHODS: We conducted a prospective, nonblinded, randomized,
      controlled trial. Inclusion criteria were blood glucose > 13.9 mmol/L, age > 18
      years, and ability to tolerate oral fluids. Subjects were excluded for critical
      illness, contraindication to fluids, and/or hyperglycemia therapy prior to
      enrolment. Subjects were randomized to receive oral bottled water or intravenous
      normal saline (maximum 2 L) over 2 hours. The primary outcome of interest was a
      change in blood glucose at 2 hours across treatment arms. RESULTS: The 48
      subjects were randomized. Baseline blood glucose levels and total amount of fluid
      received were similar between the two groups. The mean decrease in blood glucose
      at 2 hours was similar for both treatment arms: a mean decrease of 3.4 mmol/L
      (20.2 mmol/L to 16.8 mmol/L) in the oral fluid group versus a mean decrease of
      4.0 mmol/L (19.7 mmol/L to 15.7 mmol/L) in the intravenous fluid group. The mean
      difference between groups was -0.6 mmol/L (95% confidence interval -2.3-1.2; p  =
      0.51). No adverse events were observed in either group. CONCLUSION: In this
      unblinded randomized trial, oral and intravenous fluids were equally efficacious
      in lowering blood glucose levels in stable hyperglycemic patients and no adverse
      events were noted. Physicians should be mindful that, although similar, the
      reduction in blood glucose was modest in both groups.

PMID- 24852585
TI  - Socioeconomic status of emergency department users in Ontario, 2003 to 2009.
AB  - OBJECTIVE: Emergency department (ED) overcrowding in Canada is an ongoing problem
      resulting in prolonged wait times, service declines, increased patient suffering,
      and adverse patient outcomes. We explored the relationship between socioeconomic
      status (SES) and ED use in Canada's universal health care system to improve our
      understanding of the nature of ED users to both improve health care to the most
      deprived populations and reduce ED patient input. METHODS: This retrospective
      study took information from the National Ambulatory Care Reporting System (NACRS)
      database for all ED visits in Ontario between April 1, 2003, and March 31, 2010.
      As there is no direct measure of SES available from ED visit records, a proxy
      measure of SES was used, namely a deprivation index (DI) developed from material
      and social factors from the 2006 Canadian census using the patient's residential
      neighbourhood. DI scores were assigned to ED visit records using Statistics
      Canada's Postal Code Conversion File, which links postal and census geography.
      RESULTS: A total of 36,765,189 visits occurred during the study period. A cross
      province trend was found wherein the most deprived population used EDs
      disproportionately more than the least deprived population (relative risk: 1.971
      95% confidence interval 1.969-1.973, p < 0.0001). This trend was stable across
      the entire study period, although the divergence is attenuating. CONCLUSION:
      Social determinants of health clearly impact ED use patterns. People of the
      lowest SES use ED services disproportionately more than other socioeconomic
      groups. Focused health system planning and policy development directed at
      optimizing health services for the lowest SES populations are essential to
      changing ED use patterns and may be one method of decreasing ED overcrowding.

PMID- 24852586
TI  - Is lumbar puncture still needed in suspected subarachnoid hemorrhage after a
      negative head computed tomographic scan?
AB  - CLINICAL QUESTION: Is lumbar puncture still needed in suspected subarachnoid
      hemorrhage with a negative head computed tomographic scan performed within 6
      hours of headache onset? ARTICLE CHOSEN: Perry JJ, Stiell IG, Sivilotti ML, et
      al. Sensitivity of computed tomography performed within six hours of onset of
      headache for diagnosis of subarachnoid haemorrhage: prospective cohort study. BMJ
      2011;343:d4277. OBJECTIVE: To determine whether lumbar puncture can be safely
      omitted after a negative head computed tomographic scan in the workup of a
      suspected subarachnoid hemorrhage.

PMID- 24852587
TI  - Tamsulosin for treatment of unilateral distal ureterolithiasis: a systematic
      review and meta-analysis.
AB  - OBJECTIVES: The lifetime prevalence of ureterolithiasis is approximately 13% for
      men and 7% for women in the United States. Tamsulosin, an alpha-antagonist, has
      been used as therapy to facilitate the expulsion of lithiasis. Whether it is a
      good treatment for distal lithiasis remains controversial. We conducted a
      systematic review and meta-analysis to evaluate the effect of tamsulosin on the
      passage of distal ureterolithiasis. METHODS: A systematic search was conducted
      using MEDLINE, EMBASE, and Cochrane Central. Trial eligibility was evaluated by
      two investigators. All randomized controlled trials (RCTs) comparing tamsulosin
      to standard therapy or placebo for the treatment of a single distal
      ureterolithiasis <= 10 mm in adult patients with renal colic confirmed by
      radiographic imaging were included. Data extraction was conducted in duplicate.
      Primary outcome was the expulsion rate, and secondary outcomes were the mean time
      for ureterolithiasis expulsion, analgesic requirements, and side effects. Mantel
      Haenszel random effect models were used, and heterogeneity was assessed using I2
      statistics. Data were presented with relative risks (RRs). RESULTS: The search
      strategy identified 685 articles, of which 22 studies were included. Combined
      results suggested a benefit for the expulsion of ureterolithiasis (<= 10 mm) when
      tamsulosin was used compared to a standard treatment (RR 1.50 [95% CI 1.31-1.71],
      I2  =  70%). A decrease in the average time of expulsion of the ureterolithiasis
      of 3.33 days in favour of tamsulosin was observed (95% CI -4.23, -2.44], I2  = 
      67%). CONCLUSION: Tamsulosin increases the rate of spontaneous passage of distal
      ureterolithiasis (<= 10 mm).

PMID- 24852588
TI  - Improving air medical transport of the trauma patient from the ground.

PMID- 24852589
TI  - Thyrotoxic periodic paralysis triggered by beta2-adrenergic bronchodilators.
AB  - Hypokalemic periodic paralysis is the most common form of periodic paralysis and
      is characterized by attacks of muscle paralysis associated with a low serum
      potassium (K+) level due to an acute intracellular shifting. Thyrotoxic periodic
      paralysis (TPP), characterized by the triad of muscle paralysis, acute
      hypokalemia, and hyperthyroidism, is one cause of hypokalemic periodic paralysis.
      The triggering of an attack of undiagnosed TPP by beta2-adrenergic
      bronchodilators has, to our knowledge, not been reported previously. We describe
      two young men who presented to the emergency department with the sudden onset of
      muscle paralysis after administration of inhaled beta2-adrenergic bronchodilators
      for asthma. In both cases, the physical examination revealed an enlarged thyroid
      gland and symmetrical flaccid paralysis with areflexia of lower extremities.
      Hypokalemia with low urine K+ excretion and normal blood acid-base status was
      found on laboratory testing, suggestive of an intracellular shift of K+, and the
      patients' muscle strength recovered at serum K+ concentrations of 3.0 and 3.3
      mmol/L. One patient developed hyperkalemia after a total potassium chloride
      supplementation of 110 mmol. Thyroid function testing was diagnostic of primary
      hyperthyroidism due to Graves disease in both cases. These cases illustrate that
      beta2-adrenergic bronchodilators should be considered a potential precipitant of
      TPP.

PMID- 24852590
TI  - Colchicine overdose with coingestion of nonsteroidal antiinflammatory drugs.
AB  - Colchicine has a low therapeutic index. Its toxic effects generally occur at
      doses >= 0.5 mg/kg. We present the case of a 39-year-old female with toxicity
      following ingestion of 0.28 mg/kg. The patient presented to the emergency
      department (ED) with severe nausea, vomiting, and abdominal pain following an
      intentional multidrug ingestion that included colchicine, indomethacin, and
      zopiclone. Despite toxicologic management and supportive care, admission to the
      intensive care unit was required for clinical deterioration and symptom
      management. Shock and multiorgan failure resulted, with death occurring 52 hours
      postingestion. Although the toxic effects of colchicine are well documented,
      mortality caused by low doses is relatively uncommon. Management of toxicity
      consists of early diagnosis, decontamination, and supportive measures. Toxicity
      may be enhanced by drug interactions inhibiting metabolic enzymes or poor
      excretion due to renal failure. In this case, the ingestion of a nonsteroidal
      antiinflammatory drug and the associated volume depletion from the
      gastrointestinal effects of colchicine may have contributed to renal dysfunction,
      exacerbating the toxicity of colchicine. This ingestion of a relatively small
      dose of colchicine led to severe toxicity. Treatment options for colchicine
      toxicity are limited.

PMID- 24852591
TI  - The arithmetic of gestalt.

PMID- 24852593
TI  - Reflection on the Affordable Care Act (ACA) of 2010.

PMID- 24852594
TI  - Informing drug development and clinical practice through patient-centered
      outcomes research.

PMID- 24852592
TI  - Genome-wide nucleosome positioning is orchestrated by genomic regions associated
      with DNase I hypersensitivity in rice.
AB  - Nucleosome positioning dictates the DNA accessibility for regulatory proteins,
      and thus is critical for gene expression and regulation. It has been well
      documented that only a subset of nucleosomes are reproducibly positioned in
      eukaryotic genomes. The most prominent example of phased nucleosomes is the
      context of genes, where phased nucleosomes flank the transcriptional starts sites
      (TSSs). It is unclear, however, what factors determine nucleosome positioning in
      regions that are not close to genes. We mapped both nucleosome positioning and
      DNase I hypersensitive site (DHS) datasets across the rice genome. We discovered
      that DHSs located in a variety of contexts, both genic and intergenic, were
      flanked by strongly phased nucleosome arrays. Phased nucleosomes were also found
      to flank DHSs in the human genome. Our results suggest the barrier model may
      represent a general feature of nucleosome organization in eukaryote genomes.
      Specifically, regions bound with regulatory proteins, including intergenic
      regions, can serve as barriers that organize phased nucleosome arrays on both
      sides. Our results also suggest that rice DHSs often span a single, phased
      nucleosome, similar to the H2A.Z-containing nucleosomes observed in DHSs in the
      human genome. 

PMID- 24852595
TI  - Role of the patient-centered outcomes research institute in addressing
      disparities and engaging patients in clinical research.

PMID- 24852596
TI  - A community-engaged approach to quantifying caregiver preferences for the
      benefits and risks of emerging therapies for Duchenne muscular dystrophy.
AB  - BACKGROUND: There is growing agreement that regulators performing benefit-risk
      evaluations should take patients' and caregivers' preferences into consideration.
      The Patient-Focused Drug Development Initiative at the US Food and Drug
      Administration offers patients and caregivers an enhanced opportunity to
      contribute to regulatory processes by offering direct testimonials. This process
      may be advanced by providing scientific evidence regarding treatment preferences
      through engagement of a broad community of patients and caregivers. OBJECTIVE: In
      this article, we demonstrate a community-engaged approach to measure caregiver
      preferences for potential benefits and risks of emerging therapies for Duchenne
      muscular dystrophy (DMD). METHODS: An advocacy oversight team led the community
      engaged study. Caregivers' treatment preferences were measured by using best
      worst scaling (BWS). Six relevant and understandable attributes describing
      potential benefits and risks of emerging DMD therapies were identified through
      engagement with advocates (n = 5), clinicians (n = 9), drug developers from
      pharmaceutical companies and academic centers (n = 11), and other stakeholders (n
      = 5). The attributes, each defined across 3 levels, included muscle function,
      life span, knowledge about the drug, nausea, risk of bleeds, and risk of
      arrhythmia. Cognitive interviewing with caregivers (n = 7) was used to refine
      terminology and assess acceptability of the BWS instrument. The study was
      implemented through an online survey of DMD caregivers, who were recruited in the
      United States through an advocacy group and snowball sampling. Caregivers were
      presented with 18 treatment profiles, identified via a main-effect orthogonal
      experimental design, in which the dependent variable was the respondents'
      judgment as to the best and worst feature in each profile. Preference weights
      were estimated by calculating the relative number of times a feature was chosen
      as best and as worst, which were then used to estimate relative attribute
      importance. RESULTS: A total of 119 DMD caregivers completed the BWS instrument;
      they were predominately biological mothers (67.2%), married (89.9%), and white
      (91.6%). Treatment effect on muscle function was the most important among
      experimental attributes (28.7%), followed by risk of heart arrhythmia (22.4%) and
      risk of bleeding (21.2%). Having additional postapproval data was relatively the
      least important attribute (2.3%). CONCLUSIONS: We present a model process for
      advocacy organizations aiming to promote patient-centered drug development. The
      community-engaged approach was successfully used to develop and implement a
      survey to measure caregiver preferences. Caregivers were willing to accept a
      serious risk when balanced with a noncurative treatment, even absent improvement
      in life span. These preferences should inform the Food and Drug Administration's
      benefit-risk assessment of emerging DMD therapies. This study highlights the
      synergistic integration of traditional advocacy methods and scientific approach
      to quantify benefit-risk preferences.

PMID- 24852597
TI  - EVAPIL-R Scale: Continuous development and validation of a tool to assess patient
      reported tolerability of different contraceptive methods in longitudinal studies.
AB  - BACKGROUND:  OBJECTIVE: The objective of this study was to modify the EVAPIL, a
      questionnaire designed to assess user-reported tolerability of combined oral
      contraceptives (COCs) in cross-sectional studies, to make it appropriate for
      assessing the tolerability of intrauterine systems (IUSs), subdermal implants,
      and COCs in longitudinal studies. METHODS: Development of the EVAPIL-Revised
      (EVAPIL-R) was informed by a targeted literature review, qualitative interviews
      with IUS-prescribing gynecologists (n = 5), and IUS and implant users in the
      United States, Germany, and France (n = 36). RESULTS: Evidence generated supports
      the content validity of the EVAPIL-R for assessing user-reported tolerability of
      COCs, IUSs, and implants. Modifications to improve the relevance and usability of
      the questionnaire in longitudinal studies included specification of a defined
      recall period, addition of separate assessments of frequency and intensity (where
      relevant), and inclusion of additional items measuring concepts of importance to
      IUS and implant users (eg, vaginal discharge). CONCLUSIONS: The EVAPIL-R is a
      valuable tool for use in research and clinical practice to identify tolerability
      concerns in hormonal contraceptive users. Future research will evaluate the
      psychometric validity and responsiveness of the EVAPIL-R. Understanding of user
      reported tolerability of contraceptive methods is critical for facilitating
      patient adherence and potentially reducing the number of unintended pregnancies.
      The EVAPIL-R may be used to facilitate "women-centered" research and
      contraceptive counseling and provision.

PMID- 24852598
TI  - New mouse model of Alzheimer's.
AB  - Amyloid beta-peptide (Abeta) accumulation is a key characteristic of Alzheimer's
      disease (AD); therefore, mouse models of AD exhibiting Abeta pathology are
      valuable tools for unraveling disease mechanisms. However, the overexpression of
      Abeta precursor protein (APP) used in previous mouse models may cause Abeta
      independent artifacts that influence data interpretation. To circumvent these
      problems, we used an APP knock-in (KI) strategy to introduce mutations to the
      mouse APP gene to develop a new generation of AD mouse models. These new models,
      termed APP(NL-F) and APP(NL-G-F), have endogenous APP levels and develop robust
      Abeta amyloidosis, which induce synaptic degeneration and memory impairments.
      Thus, we suggest that these novel APP KI mice will serve as important tools to
      elucidate molecular mechanisms of AD. 

PMID- 24852599
TI  - Physical activity levels in women attending breast screening, receiving
      chemotherapy and post-breast cancer treatment; a cross-sectional study.
AB  - BACKGROUND: A lack of physical activity (PA) is a well-recognised risk factor in
      the development of breast cancer (BC) and evidence-base research on the impact of
      PA on BC survival is consolidating. However, evidence reveals that BC survivors
      have low levels of PA, suggesting the need of targeted interventions to enhance
      the PA behaviour of BC survivors. Unfortunately, there is lack of data from the
      UK about the PA behaviours of women at various stages of diagnosis and treatment
      of BC. Therefore, the aim of the present study was to assess PA levels in women
      at different stages of BC pathway. PATIENTS AND METHODS: A convenient sample of
      patients was selected at various stages of presentation and treatment of BC.
      Patients attending for breast screening for NHSBSP (n = 188), post-operative
      patients attending for chemotherapy (n = 41) and BC patients within one year's
      post-treatment (n = 80) were invited to take part in this cross-sectional study.
      RESULTS: Based on the odds ratio, the likelihood of a chemotherapy participant
      not meeting PA guidelines (i.e., being in the low activity category) were three
      times higher than the odds of a NHSBPS attendee not meeting PA guidelines, and
      compared to post-treatment participants, the chemotherapy patient's odds of not
      meeting PA guidelines was four times higher. The odds of NHSBPS attendees being
      in the high activity category compared to the moderate category were three times
      higher than that of a post-treatment participant. CONCLUSIONS: The current study
      suggests the need to establish robust PA interventions to enhance the PA
      behaviour of breast cancer survivors.

PMID- 24852600
TI  - Elevated white blood cell count is associated with higher risk of glucose
      metabolism disorders in middle-aged and elderly Chinese people.
AB  - White blood cell (WBC) count has been associated with diabetic risk, but whether
      the correlation is independent of other risk factors has hardly been studied.
      Moreover, very few such studies with large sample sizes have been conducted in
      Chinese. Therefore, we investigated the relationship between WBC count and
      glucose metabolism in China. We also examined the relevant variables of WBC
      count. A total of 9,697 subjects (mean age, 58.0 +/- 9.1 years) were recruited.
      The subjects were classified into four groups, including subjects with normal
      glucose tolerance, isolated impaired fasting glucose, impaired glucose tolerance
      and type 2 diabetes mellitus (T2DM). We found that WBC count increased as glucose
      metabolism disorders exacerbated. WBC count was also positively correlated with
      waist hip ratio, body mass index, smoking, triglycerides, glycosylated
      haemoglobin A1c (HbA1c) and 2-h postprandial glucose. In addition, high density
      lipoprotein and the female gender were inversely correlated with WBC levels. In
      patients with previously diagnosed T2DM, the course of T2DM was not correlated
      with WBC count. Our findings indicate that elevated WBC count is independently
      associated with worsening of glucose metabolism in middle-aged and elderly
      Chinese. In addition, loss of weight, smoking cessation, lipid-modifying
      therapies, and control of postprandial plasma glucose and HbA1c may ameliorate
      the chronic low-grade inflammation.

PMID- 24852601
TI  - Gender differences in promotion and scholarly impact: an analysis of 1460
      academic ophthalmologists.
AB  - OBJECTIVES: In recent years, gender differences in academic promotion have been
      documented within surgical fields. To the best of our knowledge, gender
      discrepancies in association with scholarly productivity have not been well
      assessed among academic ophthalmologists. Because research productivity is
      strongly associated with academic career advancement, we sought to determine
      whether gender differences in scholarly impact, measured by the h-index, exist
      among academic ophthalmologists. DESIGN: Academic rank and gender were determined
      using faculty listings from academic ophthalmology departments. h-index and
      publication experience (in years) of faculty members were determined using the
      Scopus database. SETTING: Academic medical center. RESULTS: From assistant
      professor through professor, the h-index increased with subsequent academic rank
      (p < 0.001), although between chairpersons and professors no statistical
      difference was found (p > 0.05). Overall, men had higher h-indices (h = 10.4 +/-
      0.34 standard error of mean) than women (h = 6.0 +/- 0.38 standard error of
      mean), a finding that was only statistically significant among assistant
      professors in a subgroup analysis. Women were generally underrepresented among
      senior positions. When controlling for publication range (i.e., length of time
      publishing), men had higher h-indices among those with 1 to 10 years of
      publication experience (p < 0.0001), whereas women had scholarly impact
      equivalent to and even exceeding that of men later in their careers. CONCLUSION:
      Women in academic ophthalmology continue to be underrepresented among senior
      faculty. Although women surpass men in scholarly productivity during the later
      stages of their careers, low scholarly impact during the earlier stages may
      impede academic advancement and partly explain the gender disparity in senior
      academic positions.

PMID- 24852602
TI  - Effect of UV-C radiation on bioactive compounds of pineapple (Ananas comosus L.
      Merr.) by-products.
AB  - BACKGROUND: The industrial processing of pineapple generates a high quantity of
      by-products. To reduce the environmental impact of these by-products and the
      inherent cost of their treatment, it is important to characterise and valorise
      these products, converting them into high added value products. Ultra-violet
      radiation is one of the main sustainable sanitation techniques for fruits. Since
      this radiation can induce plant stress which can promote the biosynthesis of
      bioactive compounds, it is important to evaluate its effect in fruits. RESULTS:
      The amounts of vitamins (C and E) and carotenoids (alpha-carotene, beta-carotene,
      beta-cryptoxanthin, lutein, lycopene, neoxanthin, violaxanthin and zeaxanthin) in
      pineapple by-products (core and rind) were analysed before and after treatment
      with UV radiation. All treated and untreated pineapple by-products contained beta
      carotene as the main carotenoid (rind, 2537-3225 ug; and core, 960-994 ug 100 g(
      1) DW). Pineapple rind also contained lutein (288-297 ug 100 g(-1) DW) and alpha
      carotene (89-126 ug 100 g(-1) DW). CONCLUSION: The results provide evidence of
      the potential of pineapple by-products as a source of bioactive compounds with
      antioxidant activity, which can be used by pharmaceutical, cosmetics and food
      industries. In addition, UV-C was shown to be a treatment that can add
      nutritional value to pineapple by-products.

PMID- 24852603
TI  - Sperm whales and killer whales with the largest brains of all toothed whales show
      extreme differences in cerebellum.
AB  - Among cetaceans, killer whales and sperm whales have the widest distribution in
      the world's oceans. Both species use echolocation, are long-lived, and have the
      longest periods of gestation among whales. Sperm whales dive much deeper and much
      longer than killer whales. It has long been thought that sperm whales have the
      largest brains of all living things, but our brain mass evidence, from published
      sources and our own specimens, shows that big males of these two species share
      this distinction. Despite this, we also find that cerebellum size is very
      different between killer whales and sperm whales. The sperm whale cerebellum is
      only about 7% of the total brain mass, while the killer whale cerebellum is
      almost 14%. These results are significant because they contradict claims that the
      cerebellum scales proportionally with the rest of the brain in all mammals. They
      also correct the generalization that all cetaceans have enlarged cerebella. We
      suggest possible reasons for the existence of such a large cerebellar size
      difference between these two species. Cerebellar function is not fully
      understood, and comparing the abilities of animals with differently sized
      cerebella can help uncover functional roles of the cerebellum in humans and
      animals. Here we show that the large cerebellar difference likely relates to
      evolutionary history, diving, sensory capability, and ecology.

PMID- 24852605
TI  - Interaction of autophagy and Toll-like receptors: a regulatory cross-talk--even
      in cancer cells?
AB  - Accumulating evidence indicates that the aberrantly altered process of autophagy
      is definitely involved in carcinogenesis. Nonetheless, Toll-like receptors (TLRs)
      sensing cell-derived pattern/danger-associated molecules also have the capacity
      to promote tumor development and immune escape. TLRs are usually expressed in
      immunocompetent cells, though several types of cancer cells have also been
      reported to display these innate immune receptors. On the other hand, however,
      both TLR- and autophagy-related signals may exert tumor suppressor mechanisms
      mainly in a cell-specific and context-dependent manner. The role of autophagy has
      been radically expanded, and now this machinery is considered as a fundamental
      eukaryotic cellular homeostatic process and integral component of the immune
      system influencing infection, inflammation and immunity. Recent studies have
      documented that TLRs and autophagy are interrelated in response to danger
      signals, furthermore there is a controling cross-talk among them to avoid
      deficient or excessive immunological effects. Although the potential interaction
      of autophagy and TLRs in cancer cells has not yet been clarified, it seems to be
      a critical aspect of cancer development and progression. Upon translation of
      basic knowledge into practice it is reasonable to speculate that modulation of
      the TLR-autophagy regulatory loop might be relevant for cancer treatment by
      providing further possible therapeutic targets. 

PMID- 24852604
TI  - Use of sodium butyrate as an alternative to dietary fiber: effects on the
      embryonic development and anti-oxidative capacity of rats.
AB  - In this study, we evaluated the effect of replacing dietary fiber with sodium
      butyrate on reproductive performance and antioxidant defense in a high fat diet
      during pregnancy by using a rat model. Eighty virgin female Sprague Dawley rats
      were fed one of four diets--(1) control diet (C group), (2) high fat + high fiber
      diet (HF group), (3) high-fat +5% sodium butyrate diet (SB group), and (4) HF
      diet + alpha-cyano-4-hydroxy cinnamic acid (CHC group)--intraperitoneally on days
      8, 10, 12, 14, and 16 of gestation. SB and dietary fiber had similar effects on
      improving fetal number and reducing the abortion rate; however, the anti-oxidant
      capacity of maternal serum, placenta, and fetus was superior in the HF group than
      in the SB group. In comparison, CHC injection decreased reproductive performance
      and antioxidant defense. Both dietary fiber (DF) and SB supplementation had a
      major but different effect on the expression of anti-oxidant related genes and
      nutrient transporters genes. In summary, our data indicate that SB and DF showed
      similar effect on reproductive performance, but SB cannot completely replace the
      DF towards with respect to redox regulation in high-fat diet; and SB might
      influence offspring metabolism and health differently to DF.

PMID- 24852607
TI  - High-level soluble expression of Serratia marcescens H30 lipase in Escherichia
      coli.
AB  - Serratia marcescens lipase (SmL) is an important biocatalyst used to
      enantioselectively hydrolyze (+/-)-trans-3-(4-methoxyphynyl) glycidic acid methyl
      ester. However, the economically justified level recombinant soluble expression
      of SmL in Escherichia coli has not been established. Thus, fusion genes of lipase
      from S. marcescens H30 with different fusion tags were constructed and expressed
      in E. coli. The effects of fusion tags were revealed. A significant increase in
      recombinant lipase solubility showed that E. coli BL21 (DE3)/pET32a-SmL was a
      suitable choice for SmL production. To optimize the performance of recombinant
      SmL production, changes in culture medium compositions and induction conditions
      were systematically tested. Finally, the recombinant SmL activity and
      productivity reached approximately 23,000 U/L and 1,278 U/L/H in shake flasks,
      respectively. This value is the highest SmL activity attained by heterogeneous
      recombinant expression in E. coli. Lipase activity and productivity reached
      19,650 U/L and 1,228 U/L/H, respectively, by scaling up SmL production in a 7.0 L
      fermenter. The existence of the Trx tag did not influence the chiral selectivity
      of recombinant SmL. These findings indicate a possibility for soluble and
      economical SmL expression in E. coli to meet industrial needs. 

PMID- 24852606
TI  - Domestic animal hosts strongly influence human-feeding rates of the Chagas
      disease vector Triatoma infestans in Argentina.
AB  - BACKGROUND: The host species composition in a household and their relative
      availability affect the host-feeding choices of blood-sucking insects and
      parasite transmission risks. We investigated four hypotheses regarding factors
      that affect blood-feeding rates, proportion of human-fed bugs (human blood
      index), and daily human-feeding rates of Triatoma infestans, the main vector of
      Chagas disease. METHODS: A cross-sectional survey collected triatomines in human
      sleeping quarters (domiciles) of 49 of 270 rural houses in northwestern
      Argentina. We developed an improved way of estimating the human-feeding rate of
      domestic T. infestans populations. We fitted generalized linear mixed-effects
      models to a global model with six explanatory variables (chicken blood index, dog
      blood index, bug stage, numbers of human residents, bug abundance, and maximum
      temperature during the night preceding bug catch) and three response variables
      (daily blood-feeding rate, human blood index, and daily human-feeding rate).
      Coefficients were estimated via multimodel inference with model averaging.
      FINDINGS: Median blood-feeding intervals per late-stage bug were 4.1 days, with
      large variations among households. The main bloodmeal sources were humans (68%),
      chickens (22%), and dogs (9%). Blood-feeding rates decreased with increases in
      the chicken blood index. Both the human blood index and daily human-feeding rate
      decreased substantially with increasing proportions of chicken- or dog-fed bugs,
      or the presence of chickens indoors. Improved calculations estimated the mean
      daily human-feeding rate per late-stage bug at 0.231 (95% confidence interval,
      0.157-0.305). CONCLUSIONS AND SIGNIFICANCE: Based on the changing availability of
      chickens in domiciles during spring-summer and the much larger infectivity of
      dogs compared with humans, we infer that the net effects of chickens in the
      presence of transmission-competent hosts may be more adequately described by
      zoopotentiation than by zooprophylaxis. Domestic animals in domiciles profoundly
      affect the host-feeding choices, human-vector contact rates and parasite
      transmission predicted by a model based on these estimates.

PMID- 24852608
TI  - Direct Radial LMHF Microvibration Induced Bone Formation and Promoted Implant
      Osseointegration.
AB  - BACKGROUND: Mechanical loading is known to play an important role in bone
      remodeling. PURPOSE: This study aimed to evaluate the effect of direct low
      magnitude high-frequency (LMHF) microvibration on dental implant bone formation
      and osseointegration. MATERIALS AND METHODS: Titanium implants were installed in
      rabbit tibiae. The implants in the left legs were loaded with mechanical
      vibration (15 MUm) at 10, 20, 30, and 40 Hz (10, 20, 30, and 40 Hz groups,
      respectively) for 30 minutes every day. The implants on the right legs were used
      as a sham control and did not receive a vibration load. RESULTS: After 20 days,
      the 10, 20, and 30 Hz groups showed significantly greater newly formed bone
      volume, density, ratio of the bone surface area to the trabecular bone surface
      area, and ratio of the bone surface area in direct contact with osteoclasts
      versus the total bone surface area in the region of interest compared with the
      sham control group, especially the 20 Hz group. However, the 40 Hz group did not.
      CONCLUSIONS: In conclusion, the application of direct LMHF (10, 20, or 30 Hz)
      vibration on the implants promoted bone formation and osseointegration,
      especially at 20 Hz; however, the use of 40 Hz did not result in any significant
      improvement.

PMID- 24852609
TI  - Discrimination between intact and decayed pulp regions in carious teeth by ADC
      mapping.
AB  - The aim of this study was to evaluate an advanced magnetic resonance imaging
      (MRI) method, apparent diffusion coefficient (ADC) mapping, in the functional
      assessment of carious teeth. 38 extracted human teeth with scores of 0, 3 and 6
      according to International Caries Detection and Assessment System (ICDAS)
      criteria were screened and subsequently analyzed by MRI at 2.35 T. Histology
      sectioning of teeth was used for the gold standard by analyzing two extreme cases
      (intact and severely decayed). ADC maps of the same teeth were calculated from
      corresponding diffusion-weighted images and used to obtain ADC distributions
      along dental pulp as functions of the relative pulp length measured from the
      occlusal pulp side. The measured distributions were analyzed for the best fit by
      a four-parameter three-segment linear regression model for ADC distribution along
      the pulp. MRI results were in good agreement with findings in histological
      sections of identical teeth. The best fit model parameters, relative decayed
      region depth, relative transition region width and ADC values of intact and
      decayed pulp tissue, showed statistically significant differences between the ADC
      values of intact and decayed pulp tissue (1.0 * 10(-9) m(2)/s vs. 0.74-0.89 * 10(
      9) m(2)/s) and the relative decayed region depth progressing with ICDAS score (3
      vs. 46% with ICDAS 3 vs. ICDAS 6). The results of this feasibility study
      confirmed relevance of ADC mapping for the discrimination and localization of
      intact and decayed regions in dental pulps of carious teeth.

PMID- 24852610
TI  - New ionic dinuclear Ir(III) Schiff base complexes with aggregation-induced
      phosphorescent emission (AIPE).
AB  - Two new ionic dinuclear Ir(III) Schiff base complexes which are straightforward
      to synthesise have luminescence quantum yields as high as 37% in neat films.
      These are the first examples of dinuclear ionic Ir(III) complexes that display
      aggregation-induced phosphorescent emission (AIPE).

PMID- 24852611
TI  - Effects of chemical contaminants on growth, age-structure, and reproduction of
      Mytilus edulis complex from Puget sound, Washington.
AB  - Bivalves are used as sentinel species to detect chemical contaminants in the
      marine environment, but biological effects on indigenous populations that result
      from chemical exposure are largely unknown. We assessed age-weight, length-weight
      relationships, age structure, and reproductive status (i.e. fecundity, egg size)
      of the blue mussel Mytilus edulis complex from six sites in central Puget Sound,
      Washington, and one site in the relatively pristine area of northern Puget Sound.
      Results of this study suggest that mussels from urban areas of Puget Sound
      exhibit a lower growth rate, altered population age-structure, and potential
      reproductive impairment as a result of exposure to chemical contaminants. These
      findings support the use of mussels as sentinel species to assess the biological
      effects of contaminants on invertebrate populations. 

PMID- 24852612
TI  - Composition of PM2.5 and PM1 on high and low pollution event days and its
      relation to indoor air quality in a home for the elderly.
AB  - Many studies probing the link between air quality and health have pointed towards
      associations between particulate matter (PM) exposure and decreased lung
      function, aggravation of respiratory diseases like asthma, premature death and
      increased hospitalisation admissions for the elderly and individuals with
      cardiopulmonary diseases. Of recent, it is believed that the chemical composition
      and physical properties of PM may contribute significantly to these adverse
      health effects. As part of a Belgian Science Policy project ("Health effects of
      particulate matter in relation to physical-chemical characteristics and
      meteorology"), the chemical composition (elemental and ionic compositions) and
      physical properties (PM mass concentrations) of PM were investigated, indoors and
      outdoors of old age homes in Antwerp. The case reported here specifically relates
      to high versus normal/low pollution event periods. PM mass concentrations for PM1
      and PM2.5 fractions were determined gravimetrically after collection via
      impaction. These same samples were hence analysed by EDXRF spectrometry and IC
      for their elemental and ionic compositions, respectively. During high pollution
      event days, PM mass concentrations inside the old age home reached 53 MUg m(-3)
      and 32 MUg m(-3) whilst outside concentrations were 101 MUg m(-3) and 46 MUg m(
      3) for PM2.5 and PM1, respectively. The sum of nss-sulphate, nitrate and
      ammonium, dominate the composition of PM, and contribute the most towards an
      increase in the PM during the episode days constituting 64% of ambient PM2.5 (52
      MUg m(-3)) compared to 39% on non-episode days (10 MUg m(-3)). Other PM
      components, such as mineral dust, sea salt or heavy metals were found to be
      considerably higher during PM episodes but relatively less important. Amongst
      heavy metals Zn and Pb were found at the highest concentrations in both PM2.5 and
      PM1. Acid-base ionic balance equations were calculated and point to acidic
      aerosols during event days and acidic to alkaline aerosols during non-event days.
      No significant sources of indoor pollutants could be identified inside the old
      age home as high correlations were found between outdoor and indoor PM,
      confirming mainly the outdoor origin of indoor air.

PMID- 24852613
TI  - Occurrence and source apportionment of PAHs in highly vulnerable karst system.
AB  - The concentration and spatial distribution of polycyclic aromatic hydrocarbons
      (PAHs) in topsoil, groundwater and groundwater suspended solids (SS) at Guozhuang
      karst water system of northern China were investigated. The total concentration
      of PAHs ranged from 622 to 87,880 ng/g dry weight in topsoil, from 4739 to 59,314
      ng/g dry weight in SS, and from 2137 to 9037 ng/L in groundwater, with mean
      values of 17,174 ng/g, 11,990 ng/g and 5020 ng/L, respectively. High
      concentrations of PAHs were mainly observed in the coal mining industrial area
      and the discharge area. The composition of PAHs indicated that low molecular
      weight PAHs were predominant in groundwater samples, the content of medium
      molecular weight PAHs was elevated in SS, and carcinogenic high molecular weight
      PAHs were frequently detected in topsoil. The high contents of low-medium
      molecular weight PAHs in groundwater and SS suggested relatively recent local
      sources of PAHs that were transported into the aquifer via leakage of
      contaminated surface water and/or infiltration of PAH-containing precipitation.
      The results of evaluating sources of PAHs using ratios of specific PAH compounds
      showed that PAHs mainly originated from coal and wood combustion. Furthermore,
      five sources were identified by positive matrix factorization (PMF) model, and
      the contribution to the total loadings of groundwater PAHs were: 2% for unburnt
      oil, 32% for coal combustion, 22% for vehicle emission, 27% for biomass
      combustion and 18% for coke production, respectively. Furthermore, strong
      correlations of total PAHs with total organic carbon (TOC) in topsoil indicated
      co-emission of PAHs and TOC. Poor correlations of PAHs with dissolved organic
      carbon (DOC) in groundwater indicated that other factors exert stronger
      influences. Therefore, PAHs might have posed a major threat to the quality of
      potable groundwater in Guozhuang karst water system.

PMID- 24852614
TI  - Soil nematode assemblages as bioindicators of radiation impact in the Chernobyl
      Exclusion Zone.
AB  - In radioecology, the need to understand the long-term ecological effects of
      radioactive contamination has been emphasised. This requires that the health of
      field populations is evaluated and linked to an accurate estimate of received
      radiological dose. The aim of the present study was to assess the effects of
      current radioactive contamination on nematode assemblages at sites affected by
      the fallout from the Chernobyl accident. First, we estimated the total dose rates
      (TDRs) absorbed by nematodes, from measured current soil activity concentrations,
      Dose Conversion Coefficients (DCCs, calculated using EDEN software) and soil-to
      biota concentration ratios (from the ERICA tool database). The impact of current
      TDRs on nematode assemblages was then evaluated. Nematodes were collected in
      spring 2011 from 18 forest sites in the Chernobyl Exclusion Zone (CEZ) with
      external gamma dose rates, measured using radiophotoluminescent dosimeters,
      varying from 0.2 to 22 MUGy h(-1). These values were one order of magnitude below
      the TDRs. A majority of bacterial-, plant-, and fungal-feeding nematodes and very
      few of the disturbance sensitive families were identified. No statistically
      significant association was observed between TDR values and nematode total
      abundance or the Shannon diversity index (H'). The Nematode Channel Ratio (which
      defines the relative abundance of bacterial- versus fungal-feeding nematodes)
      decreased significantly with increasing TDR, suggesting that radioactive
      contamination may influence nematode assemblages either directly or indirectly by
      modifying their food resources. A greater Maturity Index (MI), usually
      characterising better soil quality, was associated with higher pH and TDR values.
      These results suggest that in the CEZ, nematode assemblages from the forest sites
      were slightly impacted by chronic exposure at a predicted TDR of 200 MUGy h(-1).
      This may be imputable to a dominant proportion of pollutant resistant nematodes
      in all sites. This might result from a selection at the expense of sensitive
      species after the accident.

PMID- 24852615
TI  - Source apportionment of sulfate and nitrate particulate matter in the Eastern
      United States and effectiveness of emission control programs.
AB  - Reducing population exposure to PM2.5 in the eastern US will require control of
      secondary sulfate and nitrate. A source-oriented Community Multi-scale Air
      Quality (CMAQ) model is used to determine contributions of major emission sources
      to nitrate and sulfate concentrations in the seven eastern US cities (New York
      City, Pittsburgh, Baltimore, Chicago, Detroit, St. Paul, and Winston-Salem) in
      January and August of 2000 and 2006. Identified major nitrate sources include on
      road gasoline-powered vehicles, diesel engines, natural gas and coal combustion.
      From 2000 to 2006, January nitrate concentrations decreased by 25-68% for all the
      seven cities. On average, ~53% of this change was caused by emissions controls
      while 47% was caused by meteorology variations. August nitrate concentrations
      decreased by a maximum of 68% in New York City but Detroit experienced increasing
      August nitrate concentrations by up to 33%. On average, ~33% of the reduction in
      nitrate is offset by increases associated with meteorological conditions that
      favor nitrate formation. Coal combustion and natural gas are the dominant sources
      for sulfate in both seasons. January sulfate decrease from 2000 to 2006 in all
      cities by 4-58% except New York City, which increases by 13%. On average, ~93% of
      the reduction in sulfate was attributed to emission controls with 7% associated
      with changes in meteorology. August sulfate concentrations decrease by 11-44% in
      all cities. On average, emission controls alone between 2000 and 2006 would have
      caused 6% more reduction but the effectiveness of the controls was mitigated by
      meteorology conditions more favorable to sulfate production in 2006 vs. 2000. The
      results of this study suggest that regional emissions controls between 2000 and
      2006 have been effective at reducing population exposure to PM2.5 in the eastern
      US, but yearly variations in meteorology must be carefully considered when
      assessing the exact magnitude of the control benefits. 

PMID- 24852616
TI  - Uncertainty quantification and integration of machine learning techniques for
      predicting acid rock drainage chemistry: a probability bounds approach.
AB  - Acid rock drainage (ARD) is a major pollution problem globally that has adversely
      impacted the environment. Identification and quantification of uncertainties are
      integral parts of ARD assessment and risk mitigation, however previous studies on
      predicting ARD drainage chemistry have not fully addressed issues of
      uncertainties. In this study, artificial neural networks (ANN) and support vector
      machine (SVM) are used for the prediction of ARD drainage chemistry and their
      predictive uncertainties are quantified using probability bounds analysis.
      Furthermore, the predictions of ANN and SVM are integrated using four aggregation
      methods to improve their individual predictions. The results of this study showed
      that ANN performed better than SVM in enveloping the observed concentrations. In
      addition, integrating the prediction of ANN and SVM using the aggregation methods
      improved the predictions of individual techniques. 

PMID- 24852617
TI  - Diagnosis of ALK-positive anaplastic large cell lymphoma based on CD30 testing.

PMID- 24852618
TI  - Undiagnosed mycosis fungoides with transformation to large cell peripheral T-cell
      lymphoma.

PMID- 24852619
TI  - Commentary: diagnostic dilemmas that impact treatment decisions in lymphoma.

PMID- 24852620
TI  - Multilinguismo nas ciencias ambientais: Ahora ya! (Multilingualism in
      environmental sciences: it's about time!).

PMID- 24852621
TI  - Role of hypothermic machine perfusion in liver transplantation.
AB  - Machine liver perfusion has significantly evolved during the last ten years to
      optimize extended criteria liver grafts and to address the worldwide organ
      shortage. This review gives an overview on available ex vivo and in vivo data on
      hypothermic machine liver perfusion. We discuss also possible protective pathways
      and show most recent clinical applications of hypothermic machine liver perfusion
      in human. 

PMID- 24852622
TI  - Elementary mode analysis reveals that Clostridium acetobutylicum modulates its
      metabolic strategy under external stress.
AB  - Clostridium acetobutylicum is a strict anaerobe which exhibits two distinct steps
      in its metabolic network. In the first step, sugars are oxidized to organic acids
      (acetic and butyric). This is accompanied with growth. The acids produced in the
      first phase are re-assimilated into solvents (acetone, butanol, and ethanol) in
      the second phase of metabolism. The two phases are hence called acidogenesis and
      solventogenesis, respectively. In this work, using Elementary Mode Analysis
      (EMA), we quantify fluxes through Elementary Modes under different physical and
      chemical conditions. Our analysis reveals that, in response to external stresses,
      the organism invokes Elementary Modes which couple acidogenesis and
      solventogenesis. This coupling leads to the organism exhibiting characteristics
      of both, acidogenesis and solventogenesis at the same time. Significantly, this
      coupling was not invoked during any "unstressed" conditions tested in this study.
      Overall, our work highlights the flexibility in Clostridium acetobutylicum to
      modulate its metabolism to enhance chances of survival under harsh conditions. 

PMID- 24852623
TI  - Plant cold acclimation and freezing tolerance.
AB  - This introductory chapter provides a brief overview of plant freezing tolerance
      and cold acclimation and describes the basic concepts and approaches that are
      currently followed to investigate these phenomena. We highlight the
      multidisciplinary nature of these investigations and the necessity to use
      methodologies from different branches of science, such as ecology, genetics,
      physiology, biochemistry, and biophysics, to come to a complete understanding of
      the complex adaptive mechanisms underlying plant cold acclimation. 

PMID- 24852624
TI  - Measuring freezing tolerance: survival and regrowth assays.
AB  - Screening plants for freezing tolerance under tightly controlled conditions is an
      invaluable technique for studying freezing tolerance and selecting for improved
      winterhardiness. Artificial freezing tests of cereal plants historically have
      used isolated crown and stem tissue prepared by "removing all plant parts 3 cm
      above and 0.5 cm below the crown tissue" (Fowler et al., Crop Sci 21:896-901,
      1981). Here, we describe a method of conducting freezing tolerance tests using
      intact plants grown in small horticultural containers, including suggested
      methods for collecting and analyzing the data. 

PMID- 24852625
TI  - Measuring freezing tolerance: electrolyte leakage and chlorophyll fluorescence
      assays.
AB  - Quantitative assessment of freezing tolerance is essential to unravel plant
      adaptations to cold temperatures. Not only the survival of whole plants but also
      impairment of detached leaves after a freeze-thaw cycle can be used to accurately
      quantify plant freezing tolerance in terms of LT50 values. Here we describe two
      methods to determine the freezing tolerance of detached leaves using different
      physiological parameters. Firstly, we illustrate how to assess the integrity of
      (predominantly) the plasma membrane during freezing using an electrolyte leakage
      assay. Secondly, we provide a chlorophyll fluorescence imaging protocol to
      determine the freezing tolerance of the photosynthetic apparatus.

PMID- 24852626
TI  - Conducting field trials for frost tolerance breeding in cereals.
AB  - Cereal species can be damaged by frost either during winter or at flowering
      stage. Frost tolerance per se is only a part of the mechanisms that allow the
      plants to survive during winter; winterhardiness also considers other biotic or
      physical stresses that challenge the plants during the winter season limiting
      their survival rate. While frost tolerance can also be tested in controlled
      environments, winterhardiness can be determined only with field evaluations. Post
      heading frost damage occurs from radiation frost events in spring during the
      reproductive stages. A reliable evaluation of winterhardiness or of post-heading
      frost damage should be carried out with field trials replicated across years and
      locations to overcome the irregular occurrence of natural conditions which
      satisfactorily differentiate genotypes. The evaluation of post-heading frost
      damage requires a specific attention to plant phenology. The extent of frost
      damage is usually determined with a visual score at the end of the winter.

PMID- 24852627
TI  - A whole-plant screening test to identify genotypes with superior freezing
      tolerance.
AB  - Freezing tolerance is a determinant factor of persistence of perennials grown in
      northern climate. Selection for winterhardiness in field nurseries is difficult
      because of the unpredictability of occurrence of test winters allowing the
      identification of hardy genotypes. Here we describe a whole-plant assay entirely
      performed indoor in growth chambers and walk-in freezers to identify genotypes
      with superior tolerance to freezing within populations of open pollinated
      species. Three successive freezing stresses are applied to progressively
      eliminate 90 % of the population and to retain only the 10 % best performing
      genotypes. This approach can be used to generate recurrently selected populations
      more tolerant to freezing in different species.

PMID- 24852628
TI  - Mapping of quantitative trait loci (QTL) associated with plant freezing tolerance
      and cold acclimation.
AB  - Most agronomic traits are determined by quantitative trait loci (QTL) and exhibit
      continuous distribution in segregating populations. The genetic architecture and
      the hereditary characteristics of these traits are much more complicated than
      those of oligogenic traits and need adapted strategies for deciphering. The model
      plant Arabidopsis thaliana is widely studied for quantitative traits, especially
      via the utilization of natural genetic diversity. Here we describe a QTL-mapping
      protocol for analyzing freezing tolerance after cold acclimation in this species
      based on its specific genetic tools. Nevertheless, this approach can also be
      applied for the elucidation of complex traits in other plant species.

PMID- 24852629
TI  - Common garden experiments to characterize cold acclimation responses in plants
      from different climatic regions.
AB  - Cold acclimation is a crucial factor to consider in the context of ongoing
      climate change. Maladaptation with regard to frost damage and use of the growing
      season may occur depending on cold acclimation cues. Importance of photoperiod
      and preceding temperatures as cues needs therefore to be evaluated within
      (ecotypes) and among species. Common garden designs, in particular the (1)
      establishment of multiple common gardens along latitudinal/altitudinal gradients,
      (2) with in situ additional climate manipulations and (3) with manipulations in
      climate chambers are proposed as tools for the detection of local adaptations and
      relative importance of temperature and photoperiod as cues for cold adaptation.
      Here, we discuss issues in species and ecotype selection, establishment of common
      gardens including manipulations of temperature and photoperiod, and
      quantification of cold adaptation. 

PMID- 24852630
TI  - Identification of Arabidopsis mutants with altered freezing tolerance.
AB  - Low temperature is an important determinant in the configuration of natural plant
      communities and defines the range of distribution and growth of important crops.
      Some plants, including Arabidopsis, have evolved sophisticated adaptive
      mechanisms to tolerate low and freezing temperatures. Central to this adaptation
      is the process of cold acclimation. By means of this process, many plants from
      temperate regions are able to develop or increase their freezing tolerance in
      response to low, nonfreezing temperatures. The identification and
      characterization of factors involved in freezing tolerance are crucial to
      understand the molecular mechanisms underlying the cold acclimation response and
      have a potential interest to improve crop tolerance to freezing temperatures.
      Many genes implicated in cold acclimation have been identified in numerous plant
      species by using molecular approaches followed by reverse genetic analysis.
      Remarkably, however, direct genetic analyses have not been conveniently exploited
      in their capacity for identifying genes with pivotal roles in that adaptive
      response. In this chapter, we describe a protocol for evaluating the freezing
      tolerance of both non-acclimated and cold-acclimated Arabidopsis plants. This
      protocol allows the accurate and simple screening of mutant collections for the
      identification of novel factors involved in freezing tolerance and cold
      acclimation.

PMID- 24852631
TI  - Infrared thermal analysis of plant freezing processes.
AB  - Infrared thermal analysis is an invaluable technique to study the plant freezing
      process. In the differential mode infrared thermal analysis allows to localize
      ice nucleation and ice propagation in whole plants or plant samples at the tissue
      level. Ice barriers can be visualized, and supercooling of cells, tissues, and
      organs can be monitored. Places where ice masses are accommodated in the apoplast
      can be identified. Here, we describe an experimental setting developed in the
      laboratory in Innsbruck, give detailed information on the practical procedure and
      preconditions, and give additionally an idea of the problems that can be
      encountered and how they by special precautions may be overcome. 

PMID- 24852632
TI  - Cryo-scanning electron microscopy to study the freezing behavior of plant
      tissues.
AB  - A cryo-scanning electron microscope (cryo-SEM) is a valuable tool for observing
      bulk frozen samples to monitor freezing responses of plant tissues and cells.
      Here, essential processes of a cryo-SEM to observe freezing behaviors of plant
      tissue cells are described.

PMID- 24852633
TI  - Three-dimensional reconstruction of frozen and thawed plant tissues from
      microscopic images.
AB  - Histological analysis of frozen and thawed plants has been conducted for many
      years but the observation of individual sections provides only a 2-dimensional
      representation of a 3-dimensional phenomenon. Most techniques for viewing
      internal plant structure in three dimensions are either low in resolution or the
      instrument cannot penetrate deep enough into the tissue to visualize the whole
      plant. Techniques with higher resolution are expensive and equipment often
      requires time-consuming training. We present a relatively simple and less
      expensive technique using pixel-based (JPEG) images of histological sections of
      an Arabidopsis thaliana plant and commercially available software to generate 3D
      reconstructions of internal structures. The technique has proven to work just as
      effectively for images from medical histology.

PMID- 24852634
TI  - Proteomic approaches to identify cold-regulated soluble proteins.
AB  - DIGE (differential in-gel electrophoresis) is a modified version of the widely
      used 2-D gel electrophoresis (2-DE) for separation of complex protein samples.
      Two extracts to be compared are differentially labeled using fluorescent cyanine
      dyes and then separated together by 2-DE. An internal standard labeled using a
      third dye is included. This approach avoids the pitfalls of gel distortions
      frequently observed in the standard procedure, which hamper the subsequent gel
      image analysis. Inclusion of an internal standard improves the quantitative
      evaluation of the protein patterns. Using the advantages of the DIGE approach,
      impact of minor temperature differences during cold stress treatment could be
      quantitatively monitored. We will describe the application of DIGE to monitor the
      impact of cold stress on the proteome pattern of Arabidopsis. In addition to the
      separation of proteins, we will also outline how plant growth is performed.
      Finally, we will also give protocols how proteins of interest can be identified
      by MALDI-TOF- as well as ESI-MS/MS.

PMID- 24852635
TI  - Proteomic approaches to identify cold-regulated plasma membrane proteins.
AB  - Plasma membrane is the primary determinant of freezing tolerance in plants
      because of its central role in freeze-thaw cycle. Changes in the plasma membrane
      proteins have been one of the major research areas in plant cold acclimation. To
      obtain comprehensive profiles of the plasma membrane proteomes and their changes
      during the cold acclimation process, a plasma membrane purification method using
      a dextran-polyethylene glycol two polymer system and a mass spectrometry-based
      shotgun proteomics method using nano-LC-MS/MS for the plasma membrane proteins
      are described. The proteomic results obtained are further applied to label-free
      protein semiquantification.

PMID- 24852636
TI  - Profiling methods to identify cold-regulated primary metabolites using gas
      chromatography coupled to mass spectrometry.
AB  - This book chapter describes the analytical procedures required for the profiling
      of a metabolite fraction enriched for primary metabolites. The profiling is based
      on routine gas chromatography coupled to mass spectrometry (GC-MS). The generic
      profiling method is adapted to plant material, specifically to the analysis of
      single leaves from plants that were exposed to temperature stress experiments.
      The described method is modular. The modules include a rapid sampling and
      metabolic inactivation protocol for samples in a wide size range, a sample
      extraction procedure, a chemical derivatization step that is required to make the
      metabolite fraction amenable to gas chromatographic analysis, a routine GC-MS
      method, and finally the procedures of data processing and data mining. A basic
      and extendable set of standardizations for metabolite recovery and retention
      index alignment of the resulting GC-MS chromatograms is included. The method has
      two applications: (1) the rapid screening for changes of relative metabolite
      pools sizes under temperature stress and (2) the verification of cold-regulated
      metabolites by exact quantification using a GC-MS protocol with extended internal
      and external standardization. 

PMID- 24852637
TI  - A lipidomic approach to identify cold-induced changes in Arabidopsis membrane
      lipid composition.
AB  - Lipidomic analysis using electrospray ionization triple quadrupole mass
      spectrometry can be employed to monitor lipid changes that occur during cold and
      freezing stress of plants. Here we describe the analysis of Arabidopsis thaliana
      polar glycerolipids with normal and oxidized acyl chains, sampled during cold and
      freezing treatments. Mass spectral data are processed using the online
      capabilities of LipidomeDB Data Calculation Environment.

PMID- 24852638
TI  - Quantification of superoxide and hydrogen peroxide in leaves.
AB  - Reactive oxygen species (ROS) are produced in plants under both non-stressful and
      stressful conditions. Various histochemical staining methods have been developed
      and are widely used to visualize ROS accumulation sites. In contrast to
      qualitative analysis, quantification of ROS has been time- and labor consuming.
      As a consequence, the number of samples, which could be analyzed in parallel, has
      been limited. To overcome this problem, we introduce an improved semiquantitative
      method, in which ROS levels are quantified after histochemical staining in plant
      organs with the digital image analysis package ImageJ.

PMID- 24852639
TI  - Estimating ice encasement tolerance of herbage plants.
AB  - One of the key stresses acting on herbage plants during winter is ice encasement,
      when plants are enclosed in compact ice and turn from aerobic to anaerobic
      respiration. The cause of cell death is related to the accumulation of
      metabolites to toxic levels during winter and perhaps also to production of
      reactive oxygen species (ROS) when plants escape from long-lasting ice cover. The
      process of ice encasement damage has been studied by sampling studies, indirect
      measurements of ice tolerance, field tests and provocation methods by increasing
      stress in the field artificially, thus increasing the ice stress. Here we
      describe a laboratory method to measure ice encasement tolerance. This is the
      most common and effective way to measure ice encasement tolerance of large plant
      material. Plants are raised from seeds (or taken from the field), cold
      acclimated, usually at +2  degrees C under short day conditions, in a greenhouse
      or growth chamber (or in the field during fall). Plants are submerged in cold
      water in beakers and frozen encased in ice, usually at -2  degrees C. Plants are
      kept enclosed in ice at this temperature. Samples are taken at intervals,
      depending on species and tolerance of plant material, and put smoothly to
      regrowth. Damage is then evaluated after a suitable time of regeneration.

PMID- 24852640
TI  - Characterization of ice binding proteins from sea ice algae.
AB  - Several polar microalgae are able to live and thrive in the extreme environment
      found within sea ice, where growing ice crystals may cause mechanical damage to
      the cells and reduce the organisms' living space. Among the strategies adopted by
      these organisms to cope with the harsh conditions in their environment, ice
      binding proteins (IBPs) seem to play a key role and possibly contribute to their
      success in sea ice. IBPs have the ability to control ice crystal growth. In
      nature they are widespread among sea ice microalgae, and their mechanism of
      function is of interest for manifold potential applications. Here we describe
      methods for a classical determination of the IBP activity (thermal hysteresis,
      recrystallization inhibition) and further methods for protein characterization
      (ice pitting assay, determination of the nucleating temperature).

PMID- 24852641
TI  - Isolation and characterization of ice-binding proteins from higher plants.
AB  - The characterization of ice-binding proteins from plants can involve many
      techniques, only a few of which are presented here. Chief among these methods are
      tests for ice recrystallization inhibition activity. Two distinct procedures are
      described; neither is normally used for precise quantitative assays. Thermal
      hysteresis assays are used for quantitative studies but are also useful for ice
      crystal morphologies, which are important for the understanding of ice-plane
      binding. Once the sequence of interest is cloned, recombinant expression,
      necessary to verify ice-binding protein identity can present challenges, and a
      strategy for recovery of soluble, active protein is described. Lastly,
      verification of function in planta borrows from standard protocols, but with an
      additional screen applicable to ice-binding proteins. Here we have attempted to
      assist researchers wishing to isolate and characterize ice-binding proteins from
      plants with a few methods critical to success.

PMID- 24852642
TI  - A theoretical analysis of pitch stability during gliding in flying snakes.
AB  - Flying snakes use their entire body as a continuously morphing 'wing' to produce
      lift and shallow their glide trajectory. Their dominant behavior during gliding
      is aerial undulation, in which lateral waves are sent posteriorly down the body.
      This highly dynamic behavior, which is unique among animal gliders, should have
      substantial effects on the flight dynamics and stability of the snakes, resulting
      from the continuous redistribution of mass and aerodynamic forces. In this study,
      we develop two-dimensional theoretical models to assess the stability
      characteristics of snakes in the pitch direction. Previously measured force
      coefficients are used to simulate aerodynamic forces acting on the models, and
      undulation is simulated by varying mass. Model 1 is a simple three-airfoil
      representation of the snake's body that possesses a passively stable equilibrium
      solution, whose basin of stability contains initial conditions observed in
      experimental gliding trajectories. Model 2 is more sophisticated, with more
      degrees of freedom allowing for postural changes to better represent the snake's
      real kinematics; in addition, a restoring moment is added to simulate potential
      active control. The application of static and dynamic stability criteria show
      that Model 2 is passively unstable, but can be stabilized with a restoring
      moment. Overall, these models suggest that undulation does not contribute to
      stability in pitch, and that flying snakes require a closed-loop control system
      formed around a passively stable dynamical framework. 

PMID- 24852643
TI  - Quadratic Phase Couplings in the EEG of Premature and Full-term Newborn during
      Quiet Sleep.
AB  - INTRODUCTION: This article is part of the Focus Theme of Methods of Information
      in Medicine on "Biosignal Interpretation: Advanced Methods for Neural Signals and
      Images". OBJECTIVES: The aim of this study was to compare rhythmicities in the
      quadratic phase coupling (QPC) in the trace discontinue EEG patterns (TD) of
      premature newborns and the trace alternant EEG patterns (TA) of full-term
      newborns by means of time-variant bispectral analysis. Both pattern occur during
      quiet sleep and are characterized by an ongoing sequence of interburst and burst
      patterns. The courses of time-variant bispectral measures during the EEG burst
      most likely indicate specific interrelations between cortical and thalamocortical
      brain structures. METHODS: The EEG of a group of premature (n = 5) and of full
      term (n = 5) newborns was analysed. Time-variant QPC was investigated by means of
      time-variant parametric bispectral analysis. The frequency plain [0.5 Hz, 1.5 Hz]
      x [3 Hz, 6 Hz] was used as the region-of-interest (ROI). RESULTS: QPC rhythms
      with a frequency of 0.1 Hz (8 - 11 s) were found in all full-term newborns at all
      electrodes. For the premature newborns the QPC rhythms were less stable and
      slower (< 0.1 Hz, 11 -  17 s) at all electrodes and showed a higher inter
      individual variation than for the full-term newborns. Statistically, the
      adaptation of a linear mixed model revealed a difference of about 5 s between
      both groups of newborns. CONCLUSIONS: The comparison of the results of both
      groups of newborns indicates a development in the interaction between cortical,
      thalamocortical and neurovegetative structures in the neonatal brain.

PMID- 24852645
TI  - Investigation of high pressure steaming (HPS) as a thermal treatment for lipid
      extraction from Chlorella vulgaris.
AB  - Biofuels from algae are considered a technically viable energy source that
      overcomes several of the problems present in previous generations of biofuels. In
      this research high pressure steaming (HPS) was studied as a hydrothermal pre
      treatment for extraction of lipids from Chlorella vulgaris, and analysis by
      response surface methodology allowed finding operational points in terms of
      target temperature and algae concentration for high lipid and glucose yields.
      Within the range covered by these experiments the best conditions for high bio
      crude yield are temperatures higher than 174 degrees C and low biomass
      concentrations (<5 g/L). For high glucose yield there are two suitable
      operational ranges, either low temperatures (<105 degrees C) and low biomass
      concentrations (<4 g/L); or low temperatures (<105 degrees C) and high biomass
      concentrations (<110 g/L). High pressure steaming is a good hydrothermal
      treatment for lipid recovery and does not significantly change the fatty acids
      profile for the range of temperatures studied.

PMID- 24852644
TI  - Mutation in TMEM98 in a large white kindred with autosomal dominant nanophthalmos
      linked to 17p12-q12.
AB  - IMPORTANCE: Nanophthalmos is a congenital disorder characterized by small eyes,
      with the main complications being severe hyperopia and angle-closure glaucoma.
      OBJECTIVE: To perform a clinical and genetic investigation of a large white
      family with autosomal dominant nanophthalmos. DESIGN, SETTING, AND PARTICIPANTS:
      Detailed clinical evaluation and a genome-wide linkage scan was conducted in the
      family NNO-SA1. Linkage was evaluated with a 10K single-nucleotide polymorphism
      array, followed by whole exome sequencing, to identify novel segregating coding
      variants within the linked region. The candidate gene was screened for mutations
      in additional independent families by direct sequencing of the coding exons and
      intron/exon boundaries. The expression pattern of the candidate gene in ocular
      tissues was analyzed by reverse transcriptase-polymerase chain reaction.
      Participants were recruited through ophthalmology clinics at Flinders Medical
      Centre, Adelaide, South Australia, Australia. Nanophthalmos was defined as an
      axial length less than 20.0 mm and/or refractive error greater than +7.00. Of the
      35 available individuals from family NNO-SA1, 16 participants (46%) had a
      diagnosis of nanophthalmos, with mean refraction of +11.8 D and mean axial length
      of 17.6 mm. Unaffected unrelated individuals serving as controls were screened
      for the identified mutation. Additional independent families with clinically
      diagnosed nanophthalmos were also recruited. MAIN OUTCOMES AND MEASURES:
      Nanophthalmos status. RESULTS: Significant linkage was detected on chromosome 17
      between single-nucleotide polymorphism markers rs2323659 and rs967293, with a
      maximum location score of 4.1. Exome sequencing identified a single novel
      segregating missense variant within the linkage region located in exon 8 of the
      transmembrane-98 (TMEM98) gene c.577G>C (p.Ala193Pro), which was absent in the
      Exome Variant Server database and among 285 local white individuals serving as
      controls. The TMEM98 gene was expressed in all ocular tissues tested including
      sclera and optic nerve head. CONCLUSIONS AND RELEVANCE: A novel gene associated
      with nanophthalmos, TMEM98 most likely represents the cause of the disease in
      this family. To our knowledge, this represents the first gene identified causing
      autosomal dominant nanophthalmos.

PMID- 24852646
TI  - Relative extents of activity loss between enzyme-substrate interactions and
      combined environmental mechanisms.
AB  - Enzymatic hydrolysis of biomass undergoes a significant decrease in rate, which
      is often attributed to activity loss of enzyme during the incubation. Activity
      loss due to both interaction with substrate (for example inactivation of adsorbed
      enzyme) and all combined environmental mechanisms in a substrate free buffer
      solution were compared in this study. Enzyme-substrate interactions contributed
      more towards the overall activity loss than did the combined environmental
      sources as evidenced from three independent metrics. (1) Relative extents of
      inactivation were higher for enzyme-substrate interactions than for environmental
      mechanisms. (2) Apparent half-lives (1.37-11.01 h) following interaction with
      substrate were relatively small compared to environmental inactivation, which was
      21.5h. (3) The inactivation rate constant for enzyme-substrate interactions (0.56
      h(-1)) was 46 times higher than that of environmental inactivation (0.0123 h(
      1)). These results suggest enzyme-substrate interaction is the main cause of
      cellulase activity loss and contributes significantly to the slow rate of
      hydrolysis.

PMID- 24852647
TI  - Effect of arsenic on nitrification of simulated mining water.
AB  - Mining and mineral processing of gold-bearing ores often release arsenic to the
      environment. Ammonium is released when N-based explosives or cyanide are used.
      Nitrification of simulated As-rich mining waters was investigated in batch
      bioassays using nitrifying cultures enriched in a fluidized-bed reactor (FBR).
      Nitrification was maintained at 100mg AsTOT/L. In batch assays, ammonium was
      totally oxidized by the FBR enrichment in 48 h. As(III) oxidation to As(V)
      occurred during the first 3h attenuating arsenic toxicity to nitrification. At
      150 and 200mg AsTOT/L, nitrification was inhibited by 25%. Candidatus Nitrospira
      defluvii and other nitrifying species mainly colonized the FBR. In conclusion,
      the FBR enriched cultures of municipal activated sludge origins tolerated high As
      concentrations making nitrification a potent process for mining water treatment.

PMID- 24852648
TI  - Continuous xylose fermentation by Clostridium acetobutylicum--kinetics and
      energetics issues under acidogenesis conditions.
AB  - The paper reports the assessment of the growth kinetics of Clostridium
      acetobutylicum DSM 792 adopting xylose as carbon source. Xylose is the
      fundamental component of hemicellulose hydrolysis, a relevant fraction of
      lignocellulosic feedstocks for biofuel production. Tests were carried out in a
      CSTR operated under controlled pH. The effects of acids (acetic and butyric) and
      solvents (acetone, ethanol and butanol) on the fermentation were investigated.
      The conversion process was characterized under steady-state conditions in terms
      of concentration of xylose, cells, acids, and pH. The growth kinetics was
      expressed by means of a multiple product inhibition and it was able to predict
      microorganism growth rate under a broad interval of operating conditions, even
      those typical of solvents production. The mass fractional yield of biomass and
      products were expressed as a function of the specific growth rate taking into
      account the Pirt model. 

PMID- 24852649
TI  - Characterization of biocoals and dissolved organic matter phases obtained upon
      hydrothermal carbonization of brewer's spent grain.
AB  - The wet biomass brewer's spent grain was subjected to hydrothermal carbonization
      to produce biocoal. Mass balance considerations indicate for about two thirds of
      the organic carbon of the input biomass to be transferred into the biocoal. The
      van Krevelen plot refers to a high degree of defunctionalization with
      decarboxylation prevailing over dehydration. Calorific data revealed a
      significant energy densification of biocoals as compared to the input substrate.
      Sorption coefficients of organic analytes covering a wide range of
      hydrophobicities and polarities on biocoal were similar to those for dissolved
      humic acids. Data from GC/MS analysis indicated that phenols and benzenediols
      along with fatty acids released from bound lipids during the hydrothermal process
      constituted abundant products. Our findings demonstrate that the brewer's spent
      grain by-product is a good feedstock for hydrothermal carbonization to produce
      biocoal, the latter offering good prospects for energetic and soil-improving
      application fields. 

PMID- 24852651
TI  - Postural control strategies during single limb stance following acute lateral
      ankle sprain.
AB  - BACKGROUND: Single-limb stance is maintained via the integration of visual,
      vestibular and somatosensory afferents. Musculoskeletal injury challenges the
      somatosensory system to reweight distorted sensory afferents. This investigation
      supplements kinetic analysis of eyes-open and eyes-closed single-limb stance
      tasks with a kinematic profile of lower limb postural orientation in an acute
      lateral ankle sprain group to assess the adaptive capacity of the sensorimotor
      system to injury. METHODS: Sixty-six participants with first-time acute lateral
      ankle sprain completed a 20-second eyes-open single-limb stance task on their
      injured and non-injured limbs (task 1). Twenty-three of these participants
      successfully completed the same 20-second single-limb stance task with their eyes
      closed (task 2). A non-injured control group of 19 participants completed task 1,
      with 16 completing task 2. 3-dimensional kinematics of the hip, knee and ankle
      joints, as well as associated fractal dimension of the center-of-pressure path
      were determined for each limb during these tasks. FINDINGS: Between trial
      analyses revealed significant differences in stance limb kinematics and fractal
      dimension of the center-of-pressure path for task 2 only. The control group
      bilaterally assumed a position of greater hip flexion compared to injured
      participants on their side-matched "involved"(7.41 [6.1 degrees ] vs 1.44 [4.8]
      degrees ; eta(2)=.34) and "uninvolved" (9.59 [8.5 degrees ] vs 2.16 [5.6 degrees
      ]; eta(2)=.31) limbs, with a greater fractal dimension of the center-of-pressure
      path (involved limb=1.39 [0.16 degrees ] vs 1.25 [0.14 degrees ]; uninvolved
      limb=1.37 [0.21 degrees ] vs 1.23 [0.14 degrees ]). INTERPRETATION: Bilateral
      impairment in postural control strategies present following a first time acute
      lateral ankle sprain.

PMID- 24852650
TI  - The risk of serious infection in patients with rheumatoid arthritis treated with
      tumor necrosis factor inhibitors decreased over time: a report from the registry
      of Japanese rheumatoid arthritis patients on biologics for long-term safety
      (REAL) database.
AB  - To investigate changes in the risk for serious infections (SIs) over time in
      Japanese rheumatoid arthritis (RA) patients treated with tumor necrosis factor
      inhibitors (TNFIs). This prospective cohort study included Japanese RA patients
      who began treatment with a TNFI from 2005 to 2007 (2005 group, n = 716, 634.2
      patient years [PY]) and from 2008 to 2011 (2008 group, n = 352, 270.1 PY) at the
      time or after their enrollment in the registry of Japanese RA patients on
      biologics for long-term safety (REAL) database. Patients were observed for 12
      months or until discontinuation of their initial TNFI in the REAL database. Drug
      discontinuation reasons and retention rates were analyzed. Incidence rates of
      serious adverse events (SAEs) were calculated with 95 % confidence intervals
      (CIs). The Cox proportional hazard model was applied to estimate the risk for
      SIs. The retention rate in the 2008 group was significantly lower than the 2005
      group (p < 0.001). Discontinuation rates due to lack of efficacy or good control
      for the 2008 group were significantly higher than the 2005 group (p < 0.001). The
      crude incidence rate ratios comparing the 2008 group with the 2005 group for SAEs
      were 0.93 (95 % CI 0.65-1.34) and for SIs were 0.50 (0.24-1.03). The 2008 group
      had significantly lower risk for SIs than the 2005 group after adjusting for
      covariates (hazard ratio: 0.43 [0.20-0.93]). These results indicate significant
      decrease of the risk for SIs with TNFI treatment over time; this may be explained
      by evidence-based risk management of RA patients given TNFIs.

PMID- 24852653
TI  - Great news: we made MEDLINE!

PMID- 24852652
TI  - Influence of flexible fixation for open book injury after pelvic trauma--a
      biomechanical study.
AB  - BACKGROUND: Implant loosening is frequently detected after fixation of open book
      injuries. Though many authors do not see this as a complication, it is often the
      reason for hardware removal or reinstrumentation in the case of remaining
      instability. We hypothesized that the flexibility of the implant has an influence
      on loosening and thus on failure of the construct. METHODS: We used 6 fresh
      frozen pelvic specimens and tested them with our recently introduced test setup
      for two-leg alternate loading. We subjected them to a non-destructive quasi
      static test in the intact condition followed by a non-destructive cyclic test
      under axial sinusoidal loading with progressive amplitude. Afterwards we
      simulated an open book injury and performed fixation with three different
      configurations of a modular fixation system (1-, 2- or 4-rod configuration) in
      randomized order. Subsequently, the specimens were subjected to 3 cyclic tests
      with the same loading protocol as previously defined. Finally, each construct was
      cyclically tested to failure keeping the final rod configuration. FINDINGS: We
      detected significantly greater mobility after 1-rod-fixation and no significant
      differences after 2-rod or 4-rod-fixation compared to the intact symphysis
      condition. In the destructive test series the 4-rod-fixation failed first
      followed by the 1-rod-fixation. The 2-rod-fixation sustained almost 3 times as
      many load cycles prior to failure as the 4-rod-fixation, whereas the 1-rod
      fixation sustained twice as many cycles as the 4-rod-fixation. INTERPRETATION: In
      conclusion, flexible fixation of the ruptured pubic symphysis in human specimens
      shows superior behavior with respect to load bearing capacity and ability to
      withstand cyclic loading compared to stiff constructs.

PMID- 24852655
TI  - Operating mechanisms of electrolytes in magnesium ion batteries: chemical
      equilibrium, magnesium deposition, and electrolyte oxidation.
AB  - Since the early nineties there have been a number of reports on the experimental
      development of Mg electrolytes based on organo/amide-magnesium chlorides and
      their transmetalations. However, there are no theoretical papers describing the
      underlying operating mechanisms of Mg electrolytes, and there is no clear
      understanding of these mechanisms. We have therefore attempted to clarify the
      operating mechanisms of Mg electrolytes by studying the characteristics of Mg
      complexes, solvation, chemical equilibrium, Mg-deposition processes, electrolyte
      oxidation processes, and oxidative degradation mechanism of RMgCl-based
      electrolytes, using ab initio calculations. The formation and solvation energies
      of Mg complexes highly depend on the characteristics of R groups. Thus, changes
      in R groups of RMgCl lead to changes in the equilibrium position and the
      electrochemical reduction and oxidation pathways and energies. We first provide a
      methodological scheme for calculating Mg reduction potential values in non
      aqueous electrolytes and electrochemical windows. We also describe a strategy for
      designing Mg electrolytes to maximize the electrochemical windows and oxidative
      stabilities. These results will be useful not only for designing improved Mg
      electrolytes, but also for developing new electrolytes in the future. 

PMID- 24852654
TI  - Regulated genes in psoriatic skin during treatment with fumaric acid esters.
AB  - BACKGROUND: Fumaric acid esters (FAEs) are widely used in Europe for the
      treatment of psoriasis because of their clinical efficacy and favourable safety
      profile. However, the mechanisms of action by which FAEs improve psoriasis remain
      largely unknown. OBJECTIVES: To identify pathways and mechanisms affected by FAE
      treatment and to compare these with pathways affected by treatment with the
      antitumour necrosis factor (anti-TNF)-alpha biologic etanercept. METHODS: In a
      prospective cohort study, 50 patients with plaque psoriasis were treated with
      FAEs for 20 weeks. Nine patients were randomly selected for gene expression
      profiling of plaque biopsies from week 0 and week 12. The groups consisted of FAE
      responders [> Psoriasis Area and Severity Index (PASI)-75 improvement] and
      nonresponders (< PASI-50 improvement). Changes in gene expression profiles were
      analysed using Ingenuity Pathway Analysis (IPA) and the outcome was compared with
      gene expression affected by etanercept. RESULTS: Response to FAE treatment was
      associated with a >= 2-fold change (P < 0.05) in the expression of 458 genes. In
      FAE responders the role of interleukin-17A in the psoriasis pathway was most
      significantly activated. Glutathione and Nrf2 pathway molecules were specifically
      induced by FAE treatment and not by etanercept treatment, representing an FAE
      specific effect in psoriatic skin. In addition, FAE treatment specifically
      induced the transcription factors PTTG1, NR3C1, GATA3 and NFkappaBIZ in
      responding patients. CONCLUSIONS: FAE treatment induces glutathione and Nrf2
      pathway genes in lesional skin of patients with psoriasis. In responders, FAEs
      specifically regulate the transcription factors PTTG1, NR3C1, GATA3 and
      NFkappaBIZ, which are important in normal cutaneous development, and the T-helper
      (Th)2 and Th17 pathways, respectively.

PMID- 24852656
TI  - ITP-QoL questionnaire for children with immune thrombocytopenia: Italian version
      validation's.
AB  - BACKGROUND: The ITP-QoL is a disease-specific questionnaire for the assessment of
      health-related quality of life (HRQoL) in children with immune thrombocytopenia
      (ITP) and their parents. The aim of this study was to test the psychometric
      characteristics of the ITP-QoL in the Italian pediatric population in terms of
      validity and reliability. PROCEDURE: Children aged 8-16 years with acute or
      chronic ITP and their parents were recruited in Italy. Participants completed the
      ITP-QoL together with other patient-reported outcomes (PROs). Reliability was
      calculated using Cronbach's alpha. Convergent validity was determined by means of
      the Pearson correlation coefficients. RESULTS: A total of 91 ITP patients, mean
      age of 12.11 +/- 2.47 years, and their parents participated; 61.5% of the
      patients were female. Two patients had acute ITP and 30.2% had a moderate to
      severe status of ITP. Cutaneous symptoms were more frequent than mucosal
      symptoms. Due to item and scale analyses 20 items were deleted from the original
      ITP-QoL. Internal consistency of the ITP-QoL was found to be good with Cronbach's
      alpha exceeding alpha = 0.70 for all but one subscale. Concerning convergent
      validity "moderate" to "high" negative correlations were found between ITP-QoL
      and KINDL subscales. The ITP-QoL was able to discriminate between clinical
      subgroups such as number of days lost at school due to ITP and hospitalization.
      CONCLUSIONS: Our study was able to demonstrate that the Italian version of ITP
      QoL (for children aged 8-16 years) is a valid and reliable instrument for the
      assessment of HRQoL in children with ITP.

PMID- 24852657
TI  - A person-centred segmentation study in elderly care: towards efficient demand
      driven care.
AB  - Providing patients with more person-centred care without increasing costs is a
      key challenge in healthcare. A relevant but often ignored hindrance to delivering
      person-centred care is that the current segmentation of the population and the
      associated organization of healthcare supply are based on diseases. A person
      centred segmentation, i.e., based on persons' own experienced difficulties in
      fulfilling needs, is an elementary but often overlooked first step in developing
      efficient demand-driven care. This paper describes a person-centred segmentation
      study of elderly, a large and increasing target group confronted with
      heterogeneous and often interrelated difficulties in their functioning. In twenty
      five diverse healthcare and welfare organizations as well as elderly associations
      in the Netherlands, data were collected on the difficulties in biopsychosocial
      functioning experienced by 2019 older adults. Data were collected between March
      2010 and January 2011 and sampling took place based on their (temporarily) living
      conditions. Factor Mixture Model was conducted to categorize the respondents into
      segments with relatively similar experienced difficulties concerning their
      functioning. First, the analyses show that older adults can be empirically
      categorized into five meaningful segments: feeling vital; difficulties with
      psychosocial coping; physical and mobility complaints; difficulties experienced
      in multiple domains; and feeling extremely frail. The categorization seems robust
      as it was replicated in two population-based samples in the Netherlands. The
      segmentation's usefulness is discussed and illustrated through an evaluation of
      the alignment between a segment's unfulfilled biopsychosocial needs and current
      healthcare utilization. The set of person-centred segmentation variables provides
      healthcare providers the option to perform a more comprehensive first triage step
      than only a disease-based one. The outcomes of this first step could guide a
      focused and, therefore, more efficient second triage step. On a local or regional
      level, this person-centred segmentation provides input information to
      policymakers and care providers for the demand-driven allocation of resources. 

PMID- 24852658
TI  - The 'gender puzzle' of alternative medicine and holistic spirituality: a
      literature review.
AB  - Both as producers and consumers women are more likely than men to engage with
      complementary and alternative medicine (CAM) and 'New Age' holistic
      spiritualities. We conducted a literature review of sociological and
      anthropological articles, with the aim of studying why women in particular use
      and practice these alternatives, and whether using them presents an opportunity
      to challenge the conventional gender order and unequal power relations. A
      systematic search of nine databases, complemented by an informal search resulted
      in the identification of 114 articles, of which 27 were included in the review.
      The search period was limited to 2000-2013. Thematic analysis of the literature
      indicated three major trends: women draw on traditional female resources and
      perceived 'feminine' characteristics; the realm of CAM and holistic spirituality
      challenges power relations and gender inequalities in healthcare, wellbeing, and
      employment, and may serve as an emancipating, empowering alternative; however,
      factors such as lack of political support, legitimacy, and a solid institutional
      base for the field of CAM and holistic spirituality, and its use by predominantly
      white middle- and upper-class women, work against significant change in the realm
      of healthcare and limit gendered social change. We suggest that the empowerment
      women experience is a form of feminine strength and personal empowerment that
      stems from power-from-within, which is not directed toward resistance. The
      literature review reveals some lacunae in the literature that call for future
      gendered research: the lack of quantitative studies, of data concerning the
      financial success of CAM practitioners, of studies linking CAM with a feminist
      oriented analysis of the medical world, of understanding gender perceptions in
      the holistic milieu and CAM, and of studies conducted from an intersectionality
      perspective.

PMID- 24852659
TI  - Assessing the responsiveness of chronic disease care - is the World Health
      Organization's concept of health system responsiveness applicable?
AB  - The concept of health system responsiveness is an important dimension of health
      system performance assessment. Further efforts have been made in recent years to
      improve the analysis of responsiveness measurements, yet few studies have applied
      the responsiveness concept to the evaluation of specific health care delivery
      structures. The objective of this study was to test the World Health
      Organization's (WHO's) responsiveness concept for an application in the
      evaluation of chronic disease care. In September and October 2012 we conducted
      four focus groups of chronically ill people (n = 38) in Germany, in which
      participants discussed their experiences and expectations regarding health care.
      The data was analyzed deductively (on the basis of the WHO responsiveness
      concept) and inductively using directed content analysis. Ten themes related to
      health system responsiveness and one theme (finances) not directly related to
      health system responsiveness, but of high importance to the focus group
      participants, could be identified. Eight of the ten responsiveness themes are
      consistent with the WHO concept. Additionally, two new themes were identified:
      trust (consultation and treatment are not led by any motive other than the
      patients' wellbeing) and coordination (treatment involving different providers is
      coordinated and different actors communicate with each other). These findings
      indicate the suitability of the WHO responsiveness concept for the evaluation of
      chronic disease care. However, some amendments, in particular an extension of the
      concept to include the two domains trust and coordination, are necessary for a
      thorough assessment of the responsiveness of chronic disease care.

PMID- 24852661
TI  - Concussion knowledge and management practices among coaches and medical staff in
      Irish professional rugby teams.
AB  - BACKGROUND: Self-reported concussion rates among U-20 and elite rugby union
      players in Ireland are 45-48%. Half of these injuries go unreported. Accurate
      knowledge of concussion signs and symptoms and appropriate management practices
      among coaches and medical staff is important to improve the welfare of players.
      AIMS: Examine concussion knowledge among coaches, and management techniques among
      medical staff of professional Irish rugby teams. METHODS: Surveys were
      administered to 11 coaches and 12 medical staff at the end of the 2010-2011
      season. RESULTS: Coaches demonstrated an accurate knowledge of concussion with a
      good understanding of concussion-related symptoms. Medical staff reported using a
      variety of methods for assessing concussion and making return-to-play decisions.
      Reliance on subjective clinical methods was evident, with less reliance on
      objective postural stability performance. CONCLUSIONS: Overall, the coaches in
      this investigation have accurate knowledge of concussion and medical staff use
      effective techniques for managing this injury. On-going education is needed to
      assist coaches in identifying concussion signs and symptoms. It is recommended
      that medical staff increase their reliance on objective methods for assessment
      and return-to-play decision making.

PMID- 24852660
TI  - Identification of hematopoietic-specific regulatory elements from the CD45 gene
      and use for lentiviral tracking of transplanted cells.
AB  - The development of a hematopoietic reporter is crucial for determining the fate
      of lineages derived from cell-based therapies. A marking system will enable safer
      embryonic stem and induced pluripotent stem cell-based derivation of blood
      lineages and facilitate the development of efficient cellular reprogramming
      strategies based on direct fibroblast conversion. Here we report that the protein
      tyrosine phosphatase CD45 is an ideal candidate gene on which to base a
      hematopoietic reporter. CD45 regulatory elements were discovered by analyzing
      transcription factor chromatin occupancy (ChIP-seq) and promoter nuclease
      sensitivity (DNase-seq) to identify minimally sufficient sequences required for
      expression. After cloning the CD45 regulatory elements into an attenuated
      lentiviral backbone, we found that two transcriptional initiation regions were
      essential for high-level expression. Expressing CD45 promoters containing these
      regions and tethered to green fluorescent protein (GFP) in a primary B-cell
      differentiation assay and a transplantation model resulted in high levels of GFP
      in lymphoid, myeloid, and nucleated erythroid cells in mouse and human blood cell
      lineages. Moreover, GFP levels remained high 5 months after secondary
      transplantation, indicating persistence of the reporter. No CD45-driven GFP
      expression is observed after fibroblast or embryonic stem cell transduction. The
      GFP reporter is seen only after embryonic stem cells differentiate into
      hematopoietic cell progenitors and lineages, suggesting that this hematopoietic
      reporter system could be useful in validating potential autologous blood cell
      therapies.

PMID- 24852662
TI  - Fever of unknown origin in a young man.
AB  - INTRODUCTION: Sphingomonas paucimobilis bacteraemia is a rare infection typically
      related to nosocomial outbreaks. MATERIAL: A 33-year-old immunocompetent man
      requested evaluation in the Internal Medicine Department for fever without
      source. His physical examination was normal. Laboratory analysis showed mild
      hypertransaminasemia. In both blood culture sets grew Gram-negative bacilli,
      being identified as S. paucimobilis. The patient was treated with oral
      levofloxacin with full recovery. CONCLUSION: S. paucimobilis infections can occur
      in the community setting in a relatively non-immunocompromised patient. In a
      patient with bacteraemia, microbiological studies are crucial to ensure a
      successful outcome.

PMID- 24852663
TI  - Effect of intravenous dexmedetomidine-midazolam on fentanyl-induced cough.

PMID- 24852664
TI  - Static or dynamic predictors of physical activity (PA)? A tracking study based on
      12- and 38-month follow-ups in older adults.
AB  - Studies that investigated stability of PA in older populations are scarce.
      Moreover, no studies used dynamic indicators to predict PA trajectories. The
      purpose of the present study were to investigate PA stability overtime, and to
      examine if changes in self-reported physical function (dynamic indicator) are
      better predictors of trajectories of PA than baseline measures of physical
      function (static indicator). This is a prospective postal survey with two time
      point follow-ups: 12 and 38 months. Participants were older adults aged >= 60
      years, and members of the medical insurance scheme of the French national
      education system. They responded to a self-report questionnaire on PA and general
      health status at three different times: baseline, 12- and 38-month follow-ups
      (n=243 for the 12-month follow-up; n=164 for the 38-month follow-up). Overtime
      analyses of PA showed a moderate-to-good stability with regard to both duration
      and volume of PA; however, a decrease in stability for vigorous PA was found
      between 12- and 38-month follow-ups. Both baseline measure and changes in
      physical function predicted PA trajectories, but magnitudes of associations were
      stronger for the dynamic indicator. Moreover, change in physical function was the
      only predictor of both becoming active compared with Inactive (reduced
      probability) and becoming inactive compared to Active (increased probability). In
      conclusion, a dynamic indicator of physical function is a better predictor of PA
      variation than static indicators.

PMID- 24852665
TI  - "Vivre/Leben/Vivere": An interdisciplinary survey addressing progress and
      inequalities of aging over the past 30 years in Switzerland.
AB  - In this paper, we present the rationale and the design of "Vivre/Leben/Vivere"
      (VLV), a large interdisciplinary survey looking at the life and health conditions
      of individuals who are aged 65 and older and living in Switzerland. VLV is of the
      third survey of a repeated cross-sectional study, previously conducted in 1979
      and 1994 in two French-speaking areas of Switzerland (the cantons of Geneva and
      Valais). Launched in 2011, VLV extends the original design to additional German
      and Italian-speaking areas and targets a sample of 4200 individuals. Quantitative
      data are collected by means of two questionnaires and a life history calendar,
      assessing current resources in multiple spheres of the individuals' life (e.g.
      household conditions, physical and psychological health, social relations,
      participation, and values) and their accumulation across the life course. The
      objectives of VLV are twofold: first it aims to provide an updated view of life
      and health conditions of the population aged 65 and older in Switzerland, with a
      major concern in assessing diversity and inequalities. Second, VLV aims to
      compare these conditions to those observed in 1979 and 1994; hence, it aims
      providing means to question the sustainability of the positive trends, reported
      in the previous surveys. VLV is a rare opportunity in Europe to acquire
      exhaustive and cardinal knowledge about the heterogeneity of the life conditions
      of the aged and their changes over the past 30 years. 

PMID- 24852666
TI  - Perceived sleep quality is associated with depression in a Korean elderly
      population.
AB  - Our study aimed to examine the relationship between perceived sleep quality and
      depression using Pittsburgh Sleep Quality Index (PSQI) and Cole's model to
      materialize the concept of perceived sleep quality in the non-cognitively
      impaired elderly. Older adults aged 60+ were recruited from the baseline study of
      Suwon Project (SP) between 2009 and 2011 (n=2040). Perceived sleep quality was
      measured using the Korean version of the Pittsburgh Sleep Quality Index (PSQI-K),
      and depression was accessed using the Korean version of the Geriatric Depression
      Scale-Short Form (SGDS-K). We excluded the cognitively impaired elderly using the
      Korean version-Mini Mental Status Examination (K-MMSE) score less than or equal
      to 17. In multivariable adjusted logistic regression related to PSQI-K
      components, poor perceived sleep quality, including poor subjective sleep quality
      (Odds ratio (OR)=1.27, 95% confidence interval (CI)=1.01-1.61), longer sleep
      latency (OR=1.32, 95% CI=1.13-1.55) and the frequent use of sleeping medication
      (OR=1.30, 95% CI=1.10-1.53) were significantly associated with depression after
      adjusting for age, sex, education, living status, current smoking and current
      alcohol drinking, the number of comorbidity and Beck Anxiety Inventory (BAI).
      PSQI-K global score also had greater odds of reporting depression (OR=1.12, 95%
      CI=1.07-1.16). These results suggested that poor perceived sleep quality was
      associated with a greater level of depression in the elderly. 

PMID- 24852667
TI  - Association between socioeconomic status (SES), mental health and need for long
      term care (NLTC)-A Longitudinal Study among the Japanese Elderly.
AB  - This study was carried out to explore the relationship between the SES, mental
      health and the NLTC of the Japanese elderly, with the aim of providing useful
      information to lower the NLTC. A longitudinal survey was carried out in Tama
      City, Tokyo in 2001 and 2004. Data were collected from the urban-dwelling older
      adults, aged 65 years old and above, through self-reported questionnaires, which
      was participated by 7905 respondents (47.6% male and 52.4% female). Chi-square
      test, Kendall tau-b correlation analysis and structural equation modeling (SEM)
      were used to identify the association between SES, mental health and NLTC. The
      results of the SEM analysis indicated that mental health would exert a negative
      effect on NLTC for both the elderly men and the elderly women, while the effect
      was stronger for the elderly women; SES was significantly and negatively
      associated to NLTC, both for the elderly men and elderly women; a significant and
      positive relationship was observed between SES and mental health for both
      genders, but slightly stronger for the elderly men. These findings have
      implications for targeting the interventions that are aimed to delaying the NLTC
      and the financing of LTC system. 

PMID- 24852668
TI  - Sarcopenia and falls in community-dwelling elderly subjects in Japan: Defining
      sarcopenia according to criteria of the European Working Group on Sarcopenia in
      Older People.
AB  - This study assessed the association between sarcopenia (using the definition of
      the European Working Group on Sarcopenia in Older People) and fall in the past
      year among community-dwelling Japanese elderly. Subjects were 1110 community
      dwelling Japanese aged 65 or older. We used bioelectrical impedance analysis
      (BIA) to measure muscle mass, grip strength to measure muscle strength, and usual
      walking speed to measure physical performance in a baseline study. "Sarcopenia"
      was characterized by low muscle mass and low muscle strength or low physical
      performance. "Presarcopenia" was characterized only by low muscle mass. Subjects
      who did not have any of these deficiencies were classified as "normal." We then
      administered a questionnaire assessing age, sex, household status, chronic
      illness, lifestyle-related habits, and fall. This study showed the prevalence of
      fall was 16.9% and 21.3% in men and women, respectively, while that of sarcopenia
      was 13.4% and 14.9% in men and women, respectively. In men and women, the
      prevalence of sarcopenia was higher among those who had fallen. A logistic
      regression analysis using age, body fat, current drinker status, and physical
      inactivity for men, and age, body fat, smoking, and diabetes for women as
      covariate variables revealed that sarcopenia was significantly associated with a
      history of fall. The odds ratio for fall in the sarcopenia group relative to the
      normal group was 4.42 (95%CI 2.08-9.39) in men and 2.34 (95%CI 1.39-3.94) in
      women. This study revealed sarcopenia to be associated with falling in elderly
      Japanese. Sarcopenia prevention interventions may help prevent falls among
      elderly individuals. 

PMID- 24852669
TI  - Anti-inflammatory effect by exclusive enteral nutrition (EEN) in a patient with
      juvenile idiopathic arthritis (JIA): brief report.
AB  - There is extensive evidence for influence of gut microbiota on health. Exclusive
      enteral nutrition (EEN) possibly changes gut microbiota, but the exact
      pathophysiological role is unknown. EEN has been shown to have an anti
      inflammatory effect in children with Mb Crohn, an inflammatory bowel disease. The
      intestinal tract is very scarcely studied in children with juvenile idiopathic
      arthritis (JIA), but data points to an immunologically important role. The aim of
      this study was to explore if EEN had any anti-inflammatory effect in children
      with JIA. The first patient enrolled in the study was followed for 1 year. She
      had onset of severe polyarticular disease at 3.2 years of age, negative in RF,
      anti-CCP, ANA, and HLA-B27. She was included in the study at 7.4 years of age.
      Exclusive enteral nutrition was given in two periods of almost 7 weeks each,
      several months apart, during the year of the study. Clinical and laboratory
      status were assessed before, during, and after treatment periods. In this
      patient, EEN had remarkable anti-inflammatory effect that was sustained for
      months after each of two separate treatment periods. Exclusive enteral nutrition
      is a possible anti-inflammatory treatment in patients with JIA, but to what
      extent EEN is effective in other children with JIA needs to be explored, as well
      as the possible pathophysiological role of EEN in those children. 

PMID- 24852670
TI  - Detection of asymptomatic cranial neuropathies in patients with systemic lupus
      erythematosus and their relation to antiribosomal P antibody levels and disease
      activity.
AB  - The objectives of this study are to assess the risk of asymptomatic cranial
      neuropathy among patients with systemic lupus erythematosus (SLE) and find any
      association with disease activity and antiribosomal P antibodies. This study is a
      case-control study including 60 female patients and 30 healthy female controls.
      Disease activity was measured with the SLE disease activity index (SLEDAI). All
      patients were evaluated using evoked potentials, blink reflex, and levels of
      antiribosomal P antibodies. Patients with abnormal electrophysiological
      parameters had significantly higher levels of antiribosomal P antibodies (P =
      0.034) and secondary antiphospholipid syndrome (P = 0.044). Antiribosomal P
      antibodies (odds ratio 5.4, 95 % confidence interval 1.002-1.03, P = 0.002) and
      presence of anti-DNA antibodies (odds ratio 1.01, 95 % confidence interval 1.2
      24.8, P = 0.032) were independent risk factors for the presence of the abnormal
      electrophysiological parameters. Disease duration was positively correlated with
      wave 1 of the auditory brain reflex (P < 0.001) and a latency of the evoked blink
      reflex (component R1, P = 0.013). SLEDAI scores were positively correlated with
      latencies of the visually evoked potential (P100, P = 0.02), wave 1 of the
      auditory brain reflex (P < 0.001), and a latency of the evoked blink reflex (R2c,
      P = 0.005). Steroid dosage was negatively correlated with P100 latencies (P =
      0.042) and components of the evoked blink reflex (R1, P = 0.042; R2i, P = 0.041;
      R2c, P < 0.001). Because abnormalities in the visually evoked potential and blink
      reflex were associated with antiribosomal P antibodies, they can be useful for
      detecting asymptomatic cranial neuropathy. Further studies on large number of
      patients should be done to determine any association.

PMID- 24852672
TI  - Bias to pollen odors is affected by early exposure and foraging experience.
AB  - In many pollinating insects, foraging preferences are adjusted on the basis of
      floral cues learned at the foraging site. In addition, olfactory experiences
      gained at early adult stages might also help them to initially choose food
      sources. To understand pollen search behavior of honeybees, we studied how
      responses elicited by pollen-based odors are biased in foraging-age workers
      according to (i) their genetic predisposition to collect pollen, (ii) pollen
      related information gained during foraging and (iii) different experiences with
      pollen gained at early adult ages. Bees returning to the hive carrying pollen
      loads, were strongly biased to unfamiliar pollen bouquets when tested in a food
      choice device against pure odors. Moreover, pollen foragers' orientation response
      was specific to the odors emitted by the pollen type they were carrying on their
      baskets, which suggests that foragers retrieve pollen odor information to
      recognize rewarding flowers outside the hive. We observed that attraction to
      pollen odor was mediated by the exposure to a pollen diet during the first week
      of life. We did not observe the same attraction in foraging-age bees early
      exposed to an artificial diet that did not contain pollen. Contrary to the
      specific response observed to cues acquired during foraging, early exposure to
      single-pollen diets did not bias orientation response towards a specific pollen
      odor in foraging-age bees (i.e. bees chose equally between the exposed and the
      novel monofloral pollen odors). Our results show that pollen exposure at early
      ages together with olfactory experiences gained in a foraging context are both
      relevant to bias honeybees' pollen search behavior. 

PMID- 24852671
TI  - Neuropeptides affecting the transfer of juvenile hormones from males to females
      during mating in Spodoptera frugiperda.
AB  - In the polyandric moth, Spodopterafrugiperda, juvenile hormone (JH) is
      transferred from the male accessory reproductive glands (AG) to the female bursa
      copulatrix (BC) during copulation (see Hassanien et al., 2014). Here we used the
      RNA interference technique to study the role of allatoregulating neuropeptides in
      controlling the synthesis and transfer of JH during mating. Knockdown of S.
      frugiperda allatostatin C (Spofr-AS type C) in freshly emerged males leads to an
      accumulation of JH in the AG beyond that in the control and mating results in a
      higher transport of JH I and JH II into the female BC. Knockdown of S. frugiperda
      allatotropin 2 (Spofr-AT2) significantly reduces the amount of JH in the AG as
      well as its transfer into the female BC during copulation. Knockdown of S.
      frugiperda allatostatin A (Spofr-AS type A) and S. frugiperda allatotropin (Spofr
      AT; Hassanien et al., 2014) only slightly affects the accumulation of JH in the
      AG and its transfer from the male to the female. We conclude that Spofr-AS type C
      and Spofr-AT2 act as true allatostatin and true allatotropin, respectively, on
      the synthesis of JH I and JH II in the male AG. Moreover, both peptides seem to
      control the synthesis of JH III in the corpora allata of adult males and its
      release into the hemolymph. 

PMID- 24852673
TI  - Parasitization by Scleroderma guani influences protein expression in Tenebrio
      molitor pupae.
AB  - Ectoparasitoid wasps deposit their eggs onto the surface and inject venom into
      their hosts. Venoms are chemically complex and they exert substantial impact on
      hosts, including permanent or temporary paralysis and developmental arrest. These
      visible venom effects are due to changes in expression of genes encoding
      physiologically relevant proteins. While the influence of parasitization on gene
      expression in several lepidopterans has been reported, the molecular details of
      parasitoid/beetle relationships remain mostly unknown. This shortcoming led us to
      pose the hypothesis that envenomation by the ectoparasitic ant-like bethylid wasp
      Scleroderma guani leads to changes in protein expression in the yellow mealworm
      beetle Tenebrio molitor. We tested our hypothesis by comparing the proteomes of
      non-parasitized and parasitized host pupae using iTRAQ-based proteomics. We
      identified 41 proteins that were differentially expressed (32?- and 9?-regulated)
      in parasitized pupae. We assigned these proteins to functional categories,
      including immunity, stress and detoxification, energy metabolism, development,
      cytoskeleton, signaling and others. We recorded parallel changes in mRNA levels
      and protein abundance in 14 selected proteins following parasitization. Our
      findings support our hypothesis by documenting changes in protein expression in
      parasitized hosts. 

PMID- 24852674
TI  - Dimensions of religious/spiritual well-being and the dark triad of personality.
AB  - BACKGROUND: In general, religious/spiritual dimensions are found to be negatively
      correlated with all kinds of psychiatric disorders such as depression, suicidal
      ideation and substance abuse. Contrary to these findings, the goal of this study
      was to investigate the relationship between dimensions of religious/spiritual
      well-being (RSWB) and less favorable aspects of personality - the so-called 'dark
      triad' of personality traits, i.e. narcissism, machiavellianism and psychopathy -
      together with general deficits in personality structure. SAMPLING AND METHODS: A
      total of 312 college students (220 females) completed the Multidimensional
      Inventory for RSWB, the revised Narcissistic Personality Inventory, the
      Machiavellianism Inventory and the Levenson Self-Report Psychopathy Scale along
      with the 16-item Inventory of Personality Organization. RESULTS: RSWB was
      confirmed to be negatively correlated with these negative aspects of personality,
      in particular with subclinical psychopathy. More specifically, there were several
      notable overlaps; narcissism, for instance, was found to be significantly
      positively associated with some RSWB subdimensions such as 'hope' or
      'connectedness'. CONCLUSIONS: First deductions can be made from these data
      concerning an ambivalent role of spirituality in impaired personality structure.
      These associations might be further investigated especially in psychiatric
      patients diagnosed with personality disorders in order to describe potential
      psychopathological facets of religion and spirituality more adequately.

PMID- 24852675
TI  - Xanthogranulomatous prostatitis: multiparametric MRI appearances.
AB  - Granulomatous prostatitis is an unusual form of prostatitis, and
      xanthogranulomatous prostatitis (XGP) is an even rarer granulomatous
      inflammation. Very few XGP cases have been reported in the literature. The
      reports concerning MRI features of XGP are even less. The present two cases of
      XGP in our report have different appearances from previous reports and are
      accompanied by abscess. We also exhibit the magnetic resonance spectroscopy and
      dynamic contrast-enhanced MRI characteristics, which have never been reported. 

PMID- 24852676
TI  - "Swirl sign" of aggressive angiomyxoma-a lesser known diagnostic sign.
AB  - Aggressive angiomyxoma is a rare mesenchymal tumor with high rate of local
      recurrence, found mainly in the pelvis and perineum of women of reproductive-aged
      group. We present cases of two patients, with emphasis on the magnetic resonance
      (MR) imaging characteristics. The clinical presentation was nonspecific. MR
      imaging revealed characteristic "swirl sign" in T2-weighted sequence.
      Preoperative diagnosis could not be made in the first patient due to a lack of
      experience about the diagnosis. Preoperative diagnosis was made in the second
      case and was helpful for the surgeon to excise the mass completely. Aggressive
      angiomyxoma should be on the top of a differential diagnosis in the appropriate
      clinical and imaging scenario. 

PMID- 24852677
TI  - Digital breast tomosynthesis of gynecomastia and associated findings-a pictorial
      review.
AB  - Men referred for breast imaging most frequently present with a unilateral
      palpated breast lump or breast enlargement. In the vast majority of these cases,
      the cause is benign and the most common etiology is gynecomastia. This pictorial
      review illustrates the appearance by full field digital mammography and digital
      breast tomosynthesis of gynecomastia as well as additional findings in the male
      breast including sternalis muscle and hypertrophied pectoralis muscle, lipoma,
      intramammary lymph node, fat necrosis, breast cancer, and atypical ductal
      hyperplasia. 

PMID- 24852679
TI  - Three-year clinical experience with VQ SPECT for diagnosing pulmonary embolism:
      diagnostic performance.
AB  - Ventilation-perfusion (VQ) single-photon emission computed tomography (SPECT)
      comprised the administration of SmartVent (n=386) or Technegas (n=1564) and 200
      MBq (99m)Tc-MAA. 1406 scans were normal, 462 showed PE, 61 showed a singular
      subsegmental mismatched defect, 21 scans were non-diagnostic. 26% of scans
      performed with Technegas showed PE, compared to 15% with SmartVent. VQ SPECT had
      a sensitivity of 95.7%, specificity 98.6%, positive predictive value 95.7%,
      negative predictive value 98.6%. A normal VQ SPECT scan implied a more than ten
      fold lower cause-specific mortality (1 in 1406) than a scan showing PE (1 in
      116). NPV of a negative D-dimer was 94.3%. 

PMID- 24852680
TI  - Chiral spin torque arising from proximity-induced magnetization.
AB  - Domain walls can be driven by current at very high speeds in nanowires formed
      from ultra-thin, perpendicularly magnetized cobalt layers and cobalt/nickel
      multilayers deposited on platinum underlayers due to a chiral spin torque. An
      important feature of this torque is a magnetic chiral exchange field that each
      domain wall senses and that can be measured by the applied magnetic field
      amplitude along the nanowire where the domain walls stop moving irrespective of
      the magnitude of the current. Here we show that this torque is manifested when
      the magnetic layer is interfaced with metals that display a large proximity
      induced magnetization, including iridium, palladium and platinum but not gold. A
      correlation between the strength of the chiral spin torque and the proximity
      induced magnetic moment is demonstrated by interface engineering using atomically
      thin dusting layers. High domain velocities are found where there are large
      proximity-induced magnetizations in the interfaced metal layers. 

PMID- 24852678
TI  - Peritoneal chronic inflammatory mass formation due to gallstones lost during
      laparoscopic cholecystectomy.
AB  - We here describe the radiologic findings of peritoneal chronic abscess formation
      due to gallstones lost within the peritoneum during laparoscopic cholecystectomy
      (LC). A radiologic workup 7 months after LC revealed a soft-tissue mass with
      contrast enhancement, harboring internal necrosis and punctate calcium located in
      the Morrison's pouch. The mass exhibited restricted water molecule diffusion,
      absence of fat deposition, and increased F-18 fluorodeoxy-D-glucose uptake, thus
      mimicking a malignant tumor. The biopsy revealed an inflammatory granuloma.
      Another patient with similar findings was treated with percutaneous abscess
      drainage. Thus, radiologists should be aware of this disease condition and its
      imaging findings. 

PMID- 24852681
TI  - Improving access to hearing services for people with low vision: piloting a
      "hearing screening and education model" of intervention.
AB  - OBJECTIVES: The aims of this study were to investigate the potential unmet need
      for hearing services among older people attending low-vision rehabilitation, and
      pilot a "Hearing Screening and Education Model" (HSEM) of intervention to promote
      use of hearing services and aids among these individuals. DESIGN: In the Vision
      Hearing project, 300 clients attending low-vision clinics in Sydney, Australia,
      participated in baseline interviews and the HSEM (2010-2011). The HSEM consisted
      of: (1) standard pure-tone audiometry; (2) discussion of hearing loss and
      implications of dual sensory impairment; and (3) provision of information on
      hearing services and facilitated referral. Those with hearing loss who did not
      own hearing aids, reported low use (<1 hr/day), or used a single aid with
      bilateral loss were referred for full assessment by an audiologist and to the
      follow-up arm of the study (n = 210). Follow-up interviews were conducted within
      12 months to ascertain actions taken and audiological and other health outcomes.
      RESULTS: Of 169 participants in the follow-up study, 68 (40.2%) sought help for
      hearing loss within 12 months. Help-seekers had higher mean hearing handicap
      scores at baseline compared with non-help-seekers. The majority of help-seekers
      (85.3%) underwent a complete hearing assessment. Fifty-four percent (n = 37) were
      recommended hearing aids and the majority of these (n = 27) obtained new hearing
      aids. Seven participants had existing aids adjusted, and 3 obtained alternate
      assistive listening devices. Almost half of those receiving new aids or
      adjustments to hearing aids reported low use (<1 hr/day) at follow-up. Among help
      seekers, 40% were unsure or did not believe their audiologist knew of their
      visual diagnosis. Of concern, 60% of participants did not seek help largely due
      to perceptions their hearing loss was not bad enough; the presence of competing
      priorities; concerns over dealing with vision loss and managing hearing aids with
      poor vision. CONCLUSIONS: Hearing- and vision-rehabilitation services need to
      better screen for, and take account of, dual sensory impairment among their older
      clients. If audiologists are made more aware of visual conditions affecting their
      clients, they may be better placed to facilitate access to appropriate
      technologies and rehabilitation, which may improve aid retention and benefit.

PMID- 24852682
TI  - Cerebrospinal fluid beta-amyloid and phospho-tau biomarker interactions affecting
      brain structure in preclinical Alzheimer disease.
AB  - OBJECTIVE: To assess the relationships between core cerebrospinal fluid (CSF)
      biomarkers and cortical thickness (CTh) in preclinical Alzheimer disease (AD).
      METHODS: In this cross-sectional study, normal controls (n = 145) from the
      Alzheimer's Disease Neuroimaging Initiative underwent structural 3T magnetic
      resonance imaging (MRI) and lumbar puncture. CSF beta-amyloid1-42 (Abeta) and
      phospho-tau181p (p-tau) levels were measured by Luminex assays. Samples were
      dichotomized using published cutoffs (Abeta(+) /Abeta(-) and p-tau(+) /ptau(-)).
      CTh was measured by Freesurfer. CTh difference maps were derived from interaction
      and correlation analyses. Clusters from the interaction analysis were isolated to
      analyze the directionality of the interaction by analysis of covariance. RESULTS:
      We found a significant biomarker interaction between CSF Abeta and CSF p-tau
      levels affecting brain structure. Cortical atrophy only occurs in subjects with
      both Abeta(+) and p-tau(+). The stratified correlation analyses showed that the
      relationship between p-tau and CTh is modified by Abeta status and the
      relationship between Abeta and CTh is modified by p-tau status. p-Tau-dependent
      thinning was found in different cortical regions in Abeta(+) subjects but not in
      Abeta(-) subjects. Cortical thickening was related to decreasing CSF Abeta values
      in the absence of abnormal p-tau, but no correlations were found in p-tau(+)
      subjects. INTERPRETATION: Our data suggest that interactions between biomarkers
      in AD result in a 2-phase phenomenon of pathological cortical thickening
      associated with low CSF Abeta, followed by atrophy once CSF p-tau becomes
      abnormal. These interactions should be considered in clinical trials in
      preclinical AD, both when selecting patients and when using MRI as a surrogate
      marker of efficacy.

PMID- 24852683
TI  - The influence of salsolinol on basic rat metabolism.
AB  - Parkinson's disease (PD) is associated with a broad spectrum of non-motor
      symptoms, which are poorly understood and foremost, may precede motor impairment.
      These symptoms include weight changes and gastrointestinal dysregulation. In our
      experiment, we applied salsolinol given peripherally and continuously in rats to
      induce changes in the enteric nervous system, which might be similar to those
      observed in PD patients. Surprisingly, we noted decrease in body weight and
      alteration in body fat contents of the animals during salsolinol exposure. The
      blood glucose levels, lipid profile and hepatic enzymes levels were assessed as
      well. While lipid profile, postprandial blood glucose and hepatic enzymes levels
      remained indifferent, postprandial triglyceridemia was significantly lower in all
      salsolinol-treated rats in comparison with the control, which might be related to
      disturbed absorption. We also suggest that diminished body weight gain and lower
      adipose tissue accumulation in salsolinol-treated animals were due to delayed
      gastric emptying together with disturbed gut function resulting in absorptive
      dysfunction. 

PMID- 24852684
TI  - The atlanto-axial synostosis - a case of vertebral anomaly.
AB  - The subject of this analysis are the first two cervical vertebrae (the atlas and
      the axis), fused together as consequence of a pathological process. A detailed
      analysis of the specimen revealed a synostosis which existed between the lateral
      facets of the atlanto-axial joint. Hence, a fusion between the anterior arch of
      the atlas and the dens of the axis, and an incomplete ossification of the yellow
      ligaments was observed. The dimensions of the fused vertebrae, except for the
      length of the C2 vertebral foramen, remain within the normal range of variation
      for an adult male. Morphological appearance of the specimen allowed to exclude
      the congenital nature of the synostosis. Therefore we attribute a post-traumatic
      etiology to the studied anomaly. 

PMID- 24852685
TI  - The role of the histaminergic system in the central cardiovascular regulation in
      haemorrhagic hypotension.
AB  - The histaminergic system consists of neurons located in tuberomammillary nucleus
      of the posterior hypothalamus. It affects many functions of the central nervous
      system, including regulation of the brainstem cardiovascular center. In this
      paper, we present current review of the literature concerning the role of the
      histaminergic system in the cardiovascular regulation in haemorrhagic
      hypotension. Experimental studies demonstrate that in both, normotension and
      critical hemorrhagic hypotension, histamine, acting as a central
      neurotransmitter, evokes the pressor effect. Interestingly, increases in mean
      arterial pressure are significantly higher in hypovolaemic than in normovolaemic
      animals. Many lines of evidence support the hypothesis that in haemorrhagic
      shock, the histaminergic system is able to activate neural and humoral
      compensatory mechanisms involving the sympathetic nervous and renin-angiotensin
      systems, arginine vasopressin and proopiomelanocortin-derived peptides. We
      suggest that the histaminergic system could be a new target for treatment of
      hemorrhagic hypotension. 

PMID- 24852686
TI  - Hymenoptera venom allergy in humans.
AB  - Reactions to Hymenoptera stings may appear as local or systemic responses.
      According to European data, the incidence of systemic reactions to Hymenoptera
      stings in the general population is 0.3-7.5%, with the value being 0.3-0.8% in
      children and 14-43% in beekeepers. The most common systemic allergic
      (anaphylactic) reactions are caused by honeybees (Apis mellifera), and certain
      species of wasps in the family Vespidae. Severe generalized immediate-type
      allergic (anaphylactic) reactions to insect stings are of the highest clinical
      importance. They affect skin, gastrointestinal tract, respiratory and
      cardiovascular system. The classification of severity of anaphylactic reaction
      following insect stings is based on the 4-grade Mueller scale. Crucial in
      patomechanism of anaphylaxis are specific IgE antibodies directed against the
      components of the venom, which mediate the activation of mast cells, the main
      effector cells of anaphylaxis. Therapeutic management in insect venom allergy
      should be considered in the context of prophylaxis, intervention in case symptoms
      develop, prevention in the form of venom specific immunotherapy (VIT). There are
      two steps of VIT 1. Initial dose venom immunotherapy (given according to four
      protocols which differ the time to reach the maintenance dose) 2. Maintenance
      dose VIT, usually equal 100 ug. Standard treatment time should span 3-5 years.
      The main mechanisms of immune tolerance that are initiated by VIT are associated
      with: 1. a decreased reactivity of effector cells, 2. expansion of T regulatory
      lymphocytes with IL-10 expression. Therapeutic effectiveness amounts to 90-100%
      in wasp venom allergy and approximately 80% in bee venom allergy. 

PMID- 24852687
TI  - New insights into salt-sensitive hypertension.
AB  - Salt sensitivity, described as association between salt intake and blood
      pressure, varies among individuals. HSD contributes to salt-sensitive
      hypertension. Traditional view on blood pressure regulation was focused on the
      kidneys and ECV expansion secondary to body Na+ load. However, the latest data
      suggest that salt-sensitive hypertension does not primarily come about by volume
      related mechanisms and other than the renal body fluid control must play an
      important role. Since Na+ accumulation in the body does not necessarily lead to
      expansion of the extracellular volume it is suggested that Na+ might be stored in
      an osmotically inactive form either as osmotically inactive Na+ storage in the
      skin and/or osmotically neutral Na+/K+ exchange in muscle. Hypertonicity in the
      skin interstitium compared with blood and therefore osmotic stress may be a
      crucial cause of interstitial Na+ accumulation and hypertension development.
      Dietary salt loading increases osmotically inactive skin Na+ storage and
      polyanionic character of the skin, leading to local hypertonicity. The response
      to this hypertonic internal environment in the skin interstitium involves MPS
      driven and TonEBP-VEGF-C-mediated hyperplasia of lymph capillaries and increased
      eNOS expression. A decreased osmotically inactive storage capacity for Na+ or
      reduced osmotically neutral Na+/K+ exchange may predispose to marked volume
      retention, and therefore to rise in blood pressure. 

PMID- 24852688
TI  - Is the vagus nerve stimulation a way to decrease body weight in humans?
AB  - Obesity and its complications constitute an important health problem in growing
      number of people. Behavioral and pharmacological treatment is not much effective
      and surgical treatment carries too many threats. Promising method to be used is
      pharmacological or electric manipulation of vagus nerves. Regulation of food
      intake and energy utilization is a complex process regulated by centers in
      hypothalamus and brainstem which are receiving information from the peripheral
      via afferent neural pathways and sending peripherally adequate instructions by
      efferent neural pathways. In these signals conduction an important role plays
      vagus nerve. Additionally central nervous system stays under influence of
      endocrine, paracrine and neuroendocrine signals taking part in these regulations,
      functioning directly onto the centre or on the afferent neural endings. 80-90%
      fibers of vagus nerve are afferent fibers, so their action is mainly afferent,
      but possible contribution of the efferent fibers cannot be excluded. Efferent
      stimulation induces motility and secretion in the intestinal tract. Afferent
      unmyelinated C-type fibres of the vagus nerve are more sensitive and easily
      electrically stimulated. Information from vagus nerve is transmitted to nucleus
      tractus solitarius, which has projections to nucleus arcuate of the medio-basal
      hypothalamus, involved in the control of feeding behavior. It is suggested, that
      interaction onto the vagus nerve (stimulation or blocking) can be an alternative
      for other ways of obesity treatment. Through the manipulation of the vagus nerve
      activity the goal is achieved by influence on central nervous system regulating
      the energy homeostasis. 

PMID- 24852689
TI  - Chronic vagus nerve stimulation reduces body fat, blood cholesterol and
      triglyceride levels in rats fed a high-fat diet.
AB  - There is growing evidence that vagus nerve stimulation (VNS) exerts a suppressive
      effect on both short- and long-term feeding in animal models. We previously
      showed that VNS with high-frequency (10 Hz) electrical impulses decreased food
      intake and body weight in rats. In the present study, we investigated the effect
      of VNS with a low frequency (1 Hz) on the serum lipid concentrations, feeding
      behavior and appetite in rats fed a high-fat diet. The levels of appetite
      regulating peptides were also assessed. Adult male Wistar rats were
      subcutaneously implanted with a microstimulator (MS) and fed a high-fat diet
      throughout the entire study period (42 days). The left vagus nerve was stimulated
      subdiaphragmatically by rectangular electrical pulses (10 ms, 200 mV, 1 Hz, 12 h
      a day) generated by the MS. The daily food intake and body weight were measured
      each morning. At the end of the experiments, the serum glucose, cholesterol,
      triglycerides, low-density lipoproteins, high-density lipoproteins, ghrelin,
      leptin and nesfatin-1 concentrations were measured. The adipose tissue content
      was evaluated by the assessment of the weight of the epididymal fat pads. Chronic
      VNS significantly decreased food intake, body weight gain and epididymal fat pad
      weight. VNS also lowered the total plasma cholesterol concentrations and
      triglyceride levels. Finally, the serum concentrations of nesfatin-1 were
      elevated, leptin levels were decreased, and ghrelin levels remained unchanged
      after VNS. The study demonstrates that chronic electrical VNS exerts anorexigenic
      effects, lowering the blood concentration of lipids. Increased nesfatin-1 levels
      may contribute to these effects.

PMID- 24852690
TI  - Bridges of the sella turcica - anatomy and topography.
AB  - This paper presents anatomy and topography of the inconstant osseous bridges that
      may occur in the sella turcica region. The interclinoid bridge and the
      caroticoclinoid bridge can be formed in consequence of abnormal ossification of
      the dural folds or disturbances in development of the sphenoid bone. Their
      presence may be of clinical importance because of potential influence on the
      neurovascular structures passing in the vicinity of the clinoid processes of the
      sphenoid bone. 

PMID- 24852691
TI  - The immune microenvironment: a major player in human cancers.
AB  - Cancer is a major public health issue and figures among the leading causes of
      death in the world. Cancer development is a long process, involving the mutation,
      amplification or deletion of genes and chromosomal rearrangements. The
      transformed cells change morphologically, enlarge, become invasive and finally
      detach from the primary tumor to metastasize in other organs through the blood
      and/or lymph. During this process, the tumor cells interact with their
      microenvironment, which is complex and composed of stromal and immune cells that
      penetrate the tumor site via blood vessels and lymphoid capillaries. All subsets
      of immune cells can be found in tumors, but their respective density,
      functionality and organization vary from one type of tumor to another. Whereas
      inflammatory cells play a protumoral role, there is a large body of evidence of
      effector memory T cells controlling tumor invasion and metastasis. Thus, high
      densities of memory Th1/CD8 cytotoxic T cells in the primary tumors correlate
      with good prognosis in most tumor types. Tertiary lymphoid structures, which
      contain mature dendritic cells (DC) in a T cell zone, proliferating B cells and
      follicular DC, are found in the tumor stroma and they correlate with intratumoral
      Th1/CD8 T cell and B cell infiltration. Eventually, tumors undergo genetic and
      epigenetic modifications that allow them to escape being controlled by the immune
      system. This comprehensive review describes the immune contexture of human
      primary and metastatic tumors, how it impacts on patient outcomes and how it
      could be used as a predictive biomarker and guide immunotherapies.

PMID- 24852692
TI  - Risk factor analysis for bone marrow histiocytic hyperplasia with
      hemophagocytosis: an autopsy study.
AB  - The excessive release of inflammatory cytokines occasionally induces life
      threatening hemophagocytosis referred to as hemophagocytic syndrome (HPS). A
      similar condition, histiocytic hyperplasia with hemophagocytosis (HHH), is often
      seen in bone marrow collected during autopsy. Unlike HPS, the pathogenesis of HHH
      remains unclear. Therefore, we performed a clinicopathological analysis of HHH
      from 70 autopsy cases at the University of Fukui Hospital. HHH was detected in 29
      of 70 autopsies (41.4 %) and was significantly complicated with hematological
      diseases (p < 0.05) and sepsis (p < 0.05). The percentage of macrophages in bone
      marrow (BM) nucleated cells was significantly increased in HHH (p < 0.001). Data
      from medical records indicated no significant changes, except for the minimum
      values of white blood cell counts (p < 0.05) and platelet counts (p < 0.05) in
      HHH patients as compared with non-HHH patients. Concentrations of inflammatory
      mediators including IL-1beta, IL-6, and IL-8 were significantly increased in HHH
      patients. Multivariate risk factor analysis identified hematological diseases
      (odds ratio (OR), 11.71), >= 15 % BM macrophages (OR, 9.42), sepsis (OR, 7.77),
      and high serum IL-6 levels (OR, 1.00) as independent risk factors for HHH. HHH
      with hypocellular BM, the most aggressive form of HHH, was recognized in 8 of 29
      HHH patients and was associated with >= 25 % BM macrophages (p < 0.001),
      leukocytopenia (p < 0.05), and high IL-8 levels (p < 0.05). None of the HHH
      patients fulfilled the diagnostic criteria of HPS. These findings suggest that
      HHH is a different entity from HPS and that it preferentially develops under
      conditions of excessive inflammation and its associated risks, such as
      hematological diseases and sepsis.

PMID- 24852693
TI  - Bariatric surgery-induced weight loss causes remission of food addiction in
      extreme obesity.
AB  - OBJECTIVE: To test the hypotheses that bariatric surgery-induced weight loss:
      induces remission of food addiction (FA), and normalizes other eating behaviors
      associated with FA. METHODS: Forty-four obese subjects (BMI= 48 +/- 8 kg/m(2) )
      were studied before and after ~20% weight loss induced by bariatric surgery (25
      Roux-en-Y gastric bypass, 11 laparoscopic adjustable gastric banding, and eight
      sleeve gastrectomy). We assessed: FA (Yale Food Addiction Scale), food cravings
      (Food Craving Inventory), and restrictive, emotional and external eating
      behaviors (Dutch Eating Behavior Questionnaire). RESULTS: FA was identified in
      32% of subjects before surgery. Compared with non-FA subjects, those with FA
      craved foods more frequently, and had higher scores for emotional and external
      eating behaviors (all P-values <0.01; all Cohen's d >0.8). Surgery-induced weight
      loss resulted in remission of FA in 93% of FA subjects; no new cases of FA
      developed after surgery. Surgery-induced weight loss decreased food cravings, and
      emotional and external eating behaviors in both groups (all P-values < 0.001; all
      Cohen's d >= 0.8). Restrictive eating behavior did not change in non-FA subjects
      but increased in FA subjects (P < 0.01; Cohen's d>1.1). CONCLUSION: Bariatric
      surgery-induced weight loss induces remission of FA and improves several eating
      behaviors that are associated with FA.

PMID- 24852694
TI  - Elevated circulating lipasin/betatrophin in human type 2 diabetes and obesity.
AB  - Lipasin (also known as C19ORF80, RIFL, ANGPTL8 and betatrophin) is a newly
      discovered circulating factor that regulates lipid metabolism and promotes
      pancreatic beta-cell proliferation. Whether circulating levels of lipasin in
      humans are altered in a) type 2 diabetes; b) obesity and c) the postprandial
      state, however, is unknown. The current study aimed to compare serum lipasin
      levels in those who were a) non-diabetic (N=15) or diabetic (BMI- and age
      matched; N=14); b) lean or obese (N=53 totally) and c) fasting and 2 hours
      following a defined meal (N=12). Serum lipasin levels were determined by the
      enzyme-linked immunosorbent assay. Lipasin levels [mean+/-SEM] were increased by
      more than two fold (P<0.001) in the diabetic patients (5.56+/-0.73 ng/mL) as
      compared to the control subjects (2.19+/-0.24 ng/mL). Serum lipasin levels were
      positively correlated with BMI (rho=0.49, P<0.001), and showed a 35% increase 2
      hours following a defined meal (P=0.009). Therefore, lipasin/betatrophin is
      nutritionally-regulated hepatokine that is increased in human type 2 diabetes and
      obesity.

PMID- 24852695
TI  - Morphological parameters related to ruptured aneurysm in the patient with
      multiple cerebral aneurysms (clinical investigation).
AB  - OBJECTIVES: We evaluated the rupture risk of multiple cerebral aneurysms in
      aspects of various morphological parameters, and determined which parameter can
      be a reliable predictor as one aneurysm ruptured, and the others did not.
      METHODS: Between 2007 and 2012, three-dimensional (3D) angiographic images of 85
      patients harboring multiple aneurysms (85 ruptured and 104 unruptured aneurysms)
      were used to assess the following morphological parameters: geometry of the
      aneurysm itself, e.g., maximal size, aspect ratio, bottleneck ratio, height/width
      ratio, undulation, and daughter sac; architecture of the aneurysm and surrounding
      vessels, e.g. aneurysmal angle, vessel angle, inflow angle, parent-daughter
      angle, and size ratio type I & II. Univariate analysis was applied to all
      parameters, and significant parameters were identified in multivariate analysis,
      yielding the cut-off point from receiver-operating characteristic (ROC) curve
      analysis. RESULTS: On multivariate logistic regression, the aspect ratio [odds
      ratio (OR), 1.21; 95% confidence interval (CI), 1.05-1.41] and daughter sac (OR,
      3.12; 95% CI, 1.05-9.27) were significant parameters in geometries of the
      aneurysm itself. The size ratio type I (OR, 1.14; 95% CI, 1.05-1.22) and parent
      daughter angle (OR, 1.02; 95% CI, 1.00-1.04) were independent parameters in
      architecture of the aneurysm and surrounding vessels. From the ROC curve, the
      aspect ratio and size ratio type I had cut-off values of 1.3 and 1.8,
      respectively. CONCLUSION: Several morphological parameters were investigated to
      predict a rupture in multiple cerebral aneurysms using 3D angiogram. The aspect
      ratio, size ratio type I, daughter sac, and parent-daughter angle were revealed
      as competent parameters.

PMID- 24852696
TI  - Salvage therapy for recurrent glioblastoma multiforme: a multimodal approach
      combining fluorescence-guided resurgery, interstitial irradiation, and
      chemotherapy.
AB  - OBJECTIVES: Several studies have revealed that different salvage treatments in
      glioblastoma multiforme patients presenting a recurrence have limited palliative
      treatment options. The aim of this study was to evaluate the utility and
      limitations of multimodal salvage treatments in recurrent glioblastoma multiforme
      patients combining 5-aminolevulinic acid (5-ALA) fluorescence-guided resurgery,
      interstitial irradiation, and dense dose temozolomide chemotherapy (ddTMZ).
      METHODS: Seventeen consecutive patients with recurrent globlastoma multiforme
      underwent a combined scheme of salvage treatments including fluorescence-guided
      reoperation, high dose rate (HDR) brachytherapy, and ddTMZ chemotherapy and were
      included in this prospective study. This multimodal treatment group was compared
      with a 1?1 matched historical control group of 17 patients who have been treated
      with intensive temozolomide chemotherapy as the only treatment modality. All
      patients were previously treated with surgery of the primary pathology,
      concomitant, and adjuvant radiochemotherapy with temozolomide. RESULTS: Median
      follow-up was 32 months (range: 28-36 months). Median survival was 9 months for
      the entire cohort after salvage treatment and can be translated into a 3-month
      improvement in survival compared to the control group of patients with
      glioblastoma recurrence treated with temozolomide alone (P  =  0.043).
      Complications rates of multimodal salvage treatment were comparable with the
      temozolomide control group. DISCUSSION: Our experience suggests that a combined
      salvage treatment plan have the advantages of all three methods and, thus,
      provide additional survival benefit and can be considered in selected patients
      affected by recurrent high grade gliomas. Nonetheless, more cases and additional
      studies are necessary to further prove the advantages of this multimodal
      treatment.

PMID- 24852697
TI  - Inflammatory response in laparoscopic vs. open surgery for gastric cancer.
AB  - OBJECTIVE: Laparoscopic surgery may offer advantages compared to open surgery,
      such as earlier mobilization, less pain and lower post-surgical morbidity.
      Surgical stress is thought to be associated with the postoperative immunological
      changes in the body as an impaired immune function, which may lead to an
      increased susceptibility to complications and morbidity. The aim of this review
      was to investigate if laparoscopic surgery reduces the immunological response
      compared to open surgery in gastric cancer. METHODS: We conducted a literature
      search identifying relevant studies comparing laparoscopy or laparoscopic
      assisted surgery with open gastric surgery. The main outcome was postoperative
      immunological status defined as surgical stress parameters, including
      inflammatory cytokines and blood parameters. RESULTS: We identified seven studies
      that addressed the immunological status in patients undergoing laparoscopic or
      laparoscopy-assisted surgery compared to open surgery. IL-6 in circulation was
      found to be significantly reduced in laparoscopic patients. Furthermore, the
      plasma concentration of C-reactive protein was significantly lower in
      laparoscopic patients compared to patients undergoing laparotomy. Finally, most
      studies reported lower levels of white blood cell count in laparoscopic patients,
      although this result did not reach statistical significance in a small number of
      studies. CONCLUSIONS: Laparoscopy-assisted gastric surgery seems to attenuate the
      immune response compared to open surgery. Larger and prospective studies are
      needed to further evaluate if the immunological status is relatively preserved in
      minimal invasive surgery and if this may reduce the postoperative complications
      compared to open surgery.

PMID- 24852698
TI  - Assessment of genotoxicity associated with Behcet's disease using sister
      chromatid exchange assay: vitamin E versus mitomycin C.
AB  - Behcet's disease (BD) is a multisystemic chronic inflammatory disorder that
      presents throughout the world with high frequency in Turkey and Middle East. BD
      has been shown to be associated with genotoxicity as patients with the disease
      have demonstrated high rates of sister chromatid exchange (SCE) and oxidative DNA
      damage. In this study, we examined the effect of vitamin E, which is known for
      its strong antioxidant activity, on the rate of SCE in cultured lymphocytes
      obtained from BD patients. In addition, the susceptibility of patient lymphocytes
      to the mutagenic agent mitomycin C (MMC) was also investigated. The results
      showed significant elevation in the rate of SCE in lymphocytes obtained from
      patients compared to those from healthy subjects (P < 0.01). Treatment with
      vitamin E normalized the elevated rate of SCE to a comparable level observed in
      the control group (P < 0.01). Finally, treatment of cultures with MMC
      significantly increased the rate of SCE in the lymphocytes of both patients and
      controls (P < 0.001). The magnitude of change in the rate of SCE induced by MMC
      was equivalent in both groups. This result suggests similar sensitivity of BD
      lymphocytes and control ones to MMC. In conclusion, genotoxicity associated with
      BD can be overcome by treatment with vitamin E. Lymphocytes of BD have normal
      sensitivity to the mutagenic agent MMC. 

PMID- 24852699
TI  - Liver X Receptor activation delays chondrocyte hypertrophy during endochondral
      bone growth.
AB  - OBJECTIVE: Activation of the Liver X Receptor (LXR) has recently been identified
      as a therapeutic strategy for osteoarthritis (OA). Human OA articular cartilage
      explants show decreased LXR expression, and LXRbeta-null mice display OA-like
      symptoms. LXR agonist administration to OA articular cartilage explants
      suppresses proteoglycan degradation and restores LXR-activated transcription. We
      aimed to investigate the effect of LXR activation on chondrocyte differentiation
      to elucidate the molecular mechanisms behind its protection against OA. METHOD:
      The specific LXR agonist, GW3965, was used to examine the effect of LXR
      activation on chondrocyte differentiation. Tibia organ cultures were used to
      examine the effect of LXR activation on bone growth and growth plate morphology,
      followed by immunohistochemical analysis. In ATDC5 and micromass cultures,
      chondrocyte differentiation was examined through cellular staining and
      proliferation assays. Various chondrogenic markers were analyzed by real-time
      reverse-transcription polymerase chain reaction (qRT-PCR) in micromass RNA.
      RESULTS: Chondrocyte hypertrophy was suppressed by GW3965 treatment, as shown by
      decreased hypertrophic zone length in the tibial growth plate, decreased alkaline
      phosphatase staining in ATDC5 and micromass cultures, and down regulation of
      Col10a1, Mmp13 and Runx2 expression. Increased proliferation in treated ATDC5
      cells and up-regulation of Col2a1 expression in treated micromass cultures
      suggest hypertrophy is suppressed secondary to prolonged proliferation. Decreased
      p57 levels in treated growth plates suggest this to be due to cell-cycle exit
      delay. CONCLUSION: Our findings regarding LXR's role in cartilage development
      provide insight into how LXR activation prevents cartilage breakdown, further
      solidifying its potential as a therapeutic target of OA.

PMID- 24852700
TI  - Low magnitude high frequency vibration accelerated cartilage degeneration but
      improved epiphyseal bone formation in anterior cruciate ligament transect induced
      osteoarthritis rat model.
AB  - OBJECTIVES: To evaluate the effects of low-magnitude high-frequency vibration
      (LMHFV) on degenerated articular cartilage and subchondral bone in anterior
      cruciate ligament transection (ACLT) induced osteoarthritis (OA) rat model.
      METHODS: 6 months old female Sprague-Dawley rats received ACLT on right knee and
      randomly divided into treatment and control groups. OA developed 12 weeks after
      surgery. LMHFV (35 Hz, 0.3 g) treatment was given 20 min/day and 5 days/week.
      After 6, 12 and 18 weeks, six rats of each group were sacrificed at each time
      point and the right knees were harvested. OA grading score, distal femur
      cartilage volume (CV), subchondral bone morphology, elastic modulus of cartilage
      and functional changes between groups were analyzed. RESULTS: Increased cartilage
      degradation (higher OA grading score) and worse functional results (lower duty
      cycle, regular index and higher limb idleness index) were observed after LMHFV
      treatment (P = 0.011, 0.020, 0.012 and 0.005, respectively). CV increased after
      LMHFV treatment (P = 0.019). Subchondral bone density increased with OA progress
      (P < 0.01). Increased BV/TV, Tb.N and decreased Tb.Sp were observed in distal
      femur epiphysis in LMHFV treatment group (P = 0.006, 0.018 and 0.011,
      respectively). CONCLUSION: LMHFV accelerated cartilage degeneration and caused
      further functional deterioration of OA affected limb in ACLT-induced OA rat
      model. In contrast, LMHFV promoted bone formation in OA affected distal femur
      epiphysis, but did not reverse OA progression.

PMID- 24852701
TI  - Severe obstructive sleep apnoea syndrome and erectile dysfunction: a prospective
      randomised study to compare sildenafil vs. nasal continuous positive airway
      pressure.
AB  - BACKGROUND: A high incidence of erectile dysfunction (ED) among patients with
      obstructive sleep apnoea syndrome (OSAS) has been reported, with a strong
      correlation between obstructive sleep apnoea, ED, and quality of life (QOL), and
      it has been estimated that 10-60% of patients with OSAS suffer from ED. In this
      prospective randomised controlled trial, we investigated 82 men with ED
      consecutively who were referred to the outpatient clinic for sleep disorders and
      had severe OSAS (AHI> 30 events/h) without any other comorbidities as a possible
      cause of ED. The aim of this study was to evaluate and compare the efficacy of
      sildenafil vs. continuous positive airway pressure (CPAP) in men with ED and
      severe OSAS. METHODS: Eighty-two patients were randomised to two main treatment
      groups: group 1 patients (n = 41) were treated with 100-mg sildenafil 1 h before
      sexual intercourse without CPAP, and group 2 patients (n = 41 men) were treated
      with only nasal CPAP during night time sleep. Both groups were evaluated with the
      same questionnaires (International Index of Erectile Function-EF domain; Sex
      Encounter Profile; Erectile Dysfunction Inventory Treatment Satisfaction) 12
      weeks after treatment. RESULTS: In patients receiving sildenafil treatment, 58.2%
      of those who attempted sexual intercourses were successful compared to 30.4% in
      the CPAP group. The mean number of successful attempts per week was significantly
      higher in the sildenafil group compared with the CPAP group (2.9 vs. 1.7,
      respectively; p < 0.0001). The mean IIEF-EF domain scores were significantly
      higher in the sildenafil group compared with the CPAP group (p < 0.0001). The
      overall satisfaction rate was 68% with sildenafil treatment and 29% with CPAP
      treatment. CONCLUSIONS: This study confirms that severe OSAS is strongly
      associated with erectile dysfunction. CPAP and sildenafil (100 mg) are safe and
      effective therapies for OSAS-related ED patients. In the present study sildenafil
      was more effective than CPAP in treating ED associated with OSAS, as indicated by
      a significantly higher rate of successful attempts at intercourse and higher IIEF
      EF domain scores. Our study, to date, is the only that has investigated
      sildenafil in patients with severe OSAS.

PMID- 24852702
TI  - Reaction and catalyst engineering to exploit kinetically controlled whole-cell
      multistep biocatalysis for terminal FAME oxyfunctionalization.
AB  - The oxyfunctionalization of unactivated C-H bonds can selectively and efficiently
      be catalyzed by oxygenase-containing whole-cell biocatalysts. Recombinant
      Escherichia coli W3110 containing the alkane monooxygenase AlkBGT and the outer
      membrane protein AlkL from Pseudomonas putida GPo1 have been shown to efficiently
      catalyze the terminal oxyfunctionalization of renewable fatty acid methyl esters
      yielding bifunctional products of interest for polymer synthesis. In this study,
      AlkBGTL-containing E. coli W3110 is shown to catalyze the multistep conversion of
      dodecanoic acid methyl ester (DAME) via terminal alcohol and aldehyde to the
      acid, exhibiting Michaelis-Menten-type kinetics for each reaction step. In two
      liquid phase biotransformations, the product formation pattern was found to be
      controlled by DAME availability. Supplying DAME as bulk organic phase led to
      accumulation of the terminal alcohol as the predominant product. Limiting DAME
      availability via application of bis(2-ethylhexyl)phthalate (BEHP) as organic
      carrier solvent enabled almost exclusive acid accumulation. Furthermore,
      utilization of BEHP enhanced catalyst stability by reducing toxic effects of
      substrate and products. A further shift towards the overoxidized products was
      achieved by co-expression of the gene encoding the alcohol dehydrogenase AlkJ,
      which was shown to catalyze efficient and irreversible alcohol to aldehyde
      oxidation in vivo. With DAME as organic phase, the aldehyde accumulated as main
      product using resting cells containing AlkBGT, AlkL, as well as AlkJ. This study
      highlights the versatility of whole-cell biocatalysis for synthesis of
      industrially relevant bifunctional building blocks and demonstrates how
      integrated reaction and catalyst engineering can be implemented to control
      product formation patterns in biocatalytic multistep reactions.

PMID- 24852703
TI  - Complications after resection of colorectal cancer in a public hospital and a
      private hospital.
AB  - BACKGROUND: To our knowledge, immediate post-operative complication rates after
      resection of colorectal cancer (CRC) have not been compared between public and
      private hospitals in the Australian health care system. We compared the frequency
      of surgical and medical complications between a public tertiary referral hospital
      and a private hospital. METHODS: Data were drawn from a prospective registry of
      all patients having a resection for CRC between 2000 and 2010 performed by
      members of the Concord Hospital colorectal surgical unit, either at this hospital
      or at a single private hospital with which they were affiliated. Complication
      rates were compared after adjustment for preoperative and perioperative features
      by logistic regression. RESULTS: Among the 16 surgical complications, the only
      significant difference after adjustment for other features was a higher rate of
      septicaemia in the public hospital (odds ratio (OR) 2.2, 95% confidence interval
      (CI) 1.1-4.6). Among the seven medical complications, the only significant
      differences were a higher risk of cardiac complications in patients with cardiac
      co-morbidity (OR 1.8, 95% CI 1.1-3.0) and of respiratory complications in
      patients without respiratory co-morbidity (OR 3.1, 95% CI 2.2-5.9) in the public
      hospital. CONCLUSION: In this study, where the same group of surgeons performed
      all reported CRC resections in the two hospitals, no independent effect of the
      type of hospital was found on 15 of 16 surgical complications and 5 of 7 medical
      complications. Type of hospital had no impact on rates of specific complications
      apart from septicaemia and cardiorespiratory complications, which were higher in
      the public hospital.

PMID- 24852704
TI  - Well-defined "clickable" copolymers prepared via one-pot synthesis.
AB  - Well-defined "clickable" homo- and co-polymers were synthesised using a living
      polymerisation technique. Specifically propargyl methacrylate was successfully
      homo- and co-polymerised using group transfer polymerisation, GTP. This one-pot
      synthesis was performed without the need to protect the acetylenic group. Finally
      it was confirmed that the acetylenic functional group was unaffected by the
      polymerisation by clicking with azide 4-azidobenzoic acid. 

PMID- 24852705
TI  - Obstetric care in a migrant population with free access to health care.
AB  - OBJECTIVE: To evaluate differences in obstetric care between immigrant and native
      women in a country with free access to health care. METHODS: A cross-sectional
      study was carried out of immigrant mothers delivering in one of the four public
      hospitals in the Porto, Portugal, metropolitan area between February and December
      2012. The comparison group included native Portuguese mothers who delivered in
      the same institutions. The participants (89 immigrant mothers and 188 Portuguese
      mothers) were recruited by telephone and completed a written questionnaire during
      a home visit. RESULTS: Immigrant women were more likely to have their first
      pregnancy appointment after 12 weeks of pregnancy (27.0% vs 14.4%, P = 0.011) and
      to have fewer than three prenatal visits (2.2% vs 0.0%, P < 0.001). They were
      also more likely to have had a cesarean delivery (48.3% vs 31.4%, P = 0.023),
      perineal laceration (48.8% vs 11.6%, P < 0.001), or postpartum hemorrhage (33.5%
      vs 12.3%, P < 0.001). CONCLUSION: Migrants were more prone to late prenatal care
      and to intrapartum complications. Unsatisfactory interactions with healthcare
      staff may play an important role in these findings.

PMID- 24852706
TI  - Gender differences in the relationship between anxiety symptoms and physical
      inactivity in a community-based sample of adults with type 2 diabetes.
AB  - OBJECTIVE: To examine the association between physical inactivity and anxiety
      symptoms in a community-based sample of men and women with type 2 diabetes
      mellitus. METHODS: Eligibility criteria included residents of Quebec, Canada aged
      between 40 and 75 years, having a diagnosis of type 2 diabetes (<=10 years),
      being insulin-naive and having participated in a previous telephone-based survey
      of diabetes treatments. Of the 2028 eligible respondents, 1953 (96.3%) provided
      information on anxiety symptoms and were included in this analysis. Participants
      were interviewed and provided information on diabetes-related clinical and
      sociodemographic factors. RESULTS: A total of 27.3% of participants reported
      being physically inactive. The prevalence of mild to severe anxiety symptoms was
      22.9%. Persons with mild anxiety symptoms and moderate to severe anxiety symptoms
      were 1.4 times and 1.7 times more likely to report being inactive than persons
      without anxiety symptoms, respectively. Subgroup analyses according to gender
      revealed that women who had mild anxiety symptoms were 1.5 times more likely to
      report being inactive compared with women who did not have anxiety symptoms,
      whereas men who had moderate to severe anxiety symptoms were 2.5 times more
      likely to be inactive than men who did not have anxiety symptoms. CONCLUSIONS:
      Anxiety symptoms in the mild and moderate to severe range are a relevant clinical
      comorbidity in persons with type 2 diabetes, and men may represent a particularly
      vulnerable subgroup. Future research is recommended to further assess the
      relationship between anxiety symptoms and diabetes-related health behaviours.

PMID- 24852707
TI  - Enantiospecific intramolecular Heck reactions of secondary benzylic ethers.
AB  - Enantioenriched methylenecyclopentanes are synthesized by stereospecific, nickel
      catalyzed Heck cyclizations of secondary benzylic ethers. The reaction proceeds
      in high yield and enantiospecificity for benzylic ethers of both pi-extended and
      simple arenes. Ethers with pendant 1,2-disubstituted olefins form trisubstituted
      olefins with control of both absolute configuration and alkene geometry.
      Diastereoselective synthesis of a polycyclic furan is demonstrated. 

PMID- 24852715
TI  - Visible-light-induced annihilation of tumor cells with platinum-porphyrin
      conjugates.
AB  - Despite the extensive use of porphyrins in photodynamic therapy (PDT),
      tetraplatinated porphyrins have so far not been studied for their anticancer
      properties. Herein, we report the synthesis of such novel platinum-porphyrin
      conjugates as well as their photophysical characterization and in vitro light
      induced anticancer properties. These conjugates showed only minor cytotoxicity in
      the dark, but IC50 values down to 19 nM upon irradiation with light at 420
      nm.These values correspond to an excellent phototoxic index (PI=IC50 in the
      dark/IC50 in light), which reached 5000 in a cisplatin-resistant cell line. After
      incubation with HeLa cells, nuclear Pt concentrations were 30 times higher than
      with cisplatin. All of these favorable characteristics imply that tetraplatinated
      porphyrin complexes are worthy of exploration as novel PDT anticancer agents in
      vivo. 

PMID- 24852716
TI  - Combined source apportionment and degradation quantification of organic
      pollutants with CSIA: 1. Model derivation.
AB  - Compound-specific stable isotope analysis (CSIA) serves as a tool for source
      apportionment (SA) and for the quantification of the extent of degradation (QED)
      of organic pollutants. However, simultaneous occurrence of mixing of sources and
      degradation is generally believed to hamper both SA and QED. On the basis of the
      linear stable isotope mixing model and the Rayleigh equation, we developed the
      stable isotope sources and sinks model, which allows for simultaneous SA and QED
      of a pollutant that is emitted by two sources and degrades via one transformation
      process. It was shown that the model necessitates at least dual-element CSIA for
      unequivocal SA in the presence of degradation-induced isotope fractionation, as
      illustrated for perchlorate in groundwater. The model also enables QED, provided
      degradation follows instantaneous mixing of two sources. If mixing occurs after
      two sources have degraded separately, the model can still provide a conservative
      estimate of the overall extent of degradation. The model can be extended to a
      larger number of sources and sinks as outlined. It may aid in forensics and
      natural attenuation assessment of soil, groundwater, surface water, or
      atmospheric pollution. 

PMID- 24852718
TI  - Reply: Letter to the editor, Cochrane rearranged.

PMID- 24852717
TI  - Immunogenicity and safety of one dose of diphtheria, tetanus, acellular pertussis
      and poliomyelitis vaccine (Repevax(r)) followed by two doses of diphtheria,
      tetanus and poliomyelitis vaccine (Revaxis(r)) in adults aged >= 40 years not
      receiving a diphtheria- and tetanus-containing vaccination in the last 20 years.
AB  - INTRODUCTION: The immunogenicity and safety of one dose of Tdap-IPV (tetanus,
      diphtheria, acellular pertussis and inactivated poliomyelitis vaccine) and two
      doses of Td-IPV (tetanus, diphtheria and inactivated poliomyelitis vaccine) were
      assessed in adults who had not received a diphtheria- and tetanus-containing
      vaccine in the last 20 years. METHODS: This open-label, multicentre study was
      conducted in adults aged >= 40 years with no diphtheria- and tetanus-containing
      vaccine in the last 20 years. Participants received one dose of Tdap-IPV followed
      by two doses of Td-IPV (0, 1, 6 month schedule). Primary immunogenicity
      objectives: to demonstrate acceptable seroprotection rates (percentage of
      participants with antibody titre above threshold) post-dose 3 for diphtheria (>=
      0.1IU/mL by seroneutralization assay [SNA]); tetanus (>= 0.1IU/mL by enzyme
      linked immunosorbent assay [ELISA]); and poliomyelitis (>= 8 1/dil by SNA); and
      to evaluate the percentage of participants with an antibody concentration >=
      5EU/mL (by ELISA) for pertussis antigens post-dose 1. Seroprotection rates were
      acceptable if the lower limit of the 95% confidence interval (CI) was >95%.
      Percentage of participants with basic clinical immunity against diphtheria (>=
      0.01IU/mL) was also assessed. Safety (adverse events [AEs] and serious AEs) was
      assessed after each dose. RESULTS: Overall, 336 participants were included (mean
      age: 60.2 years). Post-dose 3 seroprotection rates were: diphtheria, 94.6% (CI
      91.5-96.8); tetanus and poliomyelitis, 100% (CI: 98.8-100). Percentage of
      participants with an antibody titre >= 5EU/mL against pertussis antigens was >=
      95.8% for all five pertussis components. Basic clinical immunity against
      diphtheria was achieved in 100% (CI: 98.8-100) of participants. AEs were reported
      more frequently following vaccination with Tdap-IPV (post-dose 1: 65.3%) than
      with Td-IPV (post-dose 2: 48.3%; post-dose 3: 50.3%). CONCLUSIONS: This study
      highlights the benefits of using Tdap-IPV followed by two doses of Td-IPV in an
      adult population to achieve maximal protection against diphtheria, tetanus,
      poliomyelitis and pertussis simultaneously.

PMID- 24852719
TI  - How very young men who have sex with men view vaccination against human
      papillomavirus.
AB  - BACKGROUND: HPV vaccination of men who have sex with men (MSM) prior to the
      commencement of sexual activity would have the maximum impact on preventing HPV
      and anal cancer in this population. However, knowledge and attitudes towards HPV
      vaccination among very young MSM have not been previously studied. METHODS: Two
      hundred MSM aged 16 to 20 were recruited via community and other sources.
      Participants were asked about their knowledge and attitudes towards HPV and HPV
      vaccination. RESULTS: Most (80%, 95% confidence interval (CI) 72.2-87.2%) men
      were not willing to purchase the vaccine because of its cost (AUD$450). However,
      if the vaccine was offered to MSM free of charge, 86% (95% CI: 80-90%) reported
      they would be willing to disclose their sexuality to a health care provider in
      order to obtain the vaccine. Over half (54%, 95%: 47-61%) of men would only be
      willing to disclose their sexuality to receive the HPV vaccine after their first
      experience of anal intercourse. The age at first insertive anal intercourse and
      the age at first receptive anal intercourse were 0.21 (IQR: -2.5 to 3.2) and 0.17
      (IQR: -2.9 to 2.7) years earlier than the age that men would be willing to
      disclose their sexuality to receive the HPV vaccine, respectively. Willingness to
      receive the vaccine at a younger age was associated with younger age at first
      insertive anal intercourse. CONCLUSION: Overall, very young MSM expressed high
      acceptance of HPV vaccination. Early, opportunistic vaccination of very young MSM
      may be feasible in settings where very young MSM have not been vaccinated through
      universal programs targeting school aged males. However, given HPV infections
      occur early on, the effectiveness of this approach will be less than vaccination
      targeting school aged boys.

PMID- 24852720
TI  - Report of the Third European Expert Meeting on Rotavirus Vaccination: Progress in
      rotavirus universal mass vaccination in Europe.

PMID- 24852721
TI  - Vaccines and vaccination against yellow fever: WHO Position Paper, June 2013-
      recommendations.
AB  - This article presents the World Health Organizations (WHO) evidence and
      recommendations for the use of yellow fever (YF) vaccination from "Vaccines and
      vaccination against yellow fever: WHO Position Paper - June 2013" published in
      the Weekly Epidemiological Record. This position paper summarizes the WHO
      position on the use of YF vaccination, in particular that a single dose of YF
      vaccine is sufficient to confer sustained life-long protective immunity against
      YF disease. A booster dose is not necessary. The current document replaces the
      position paper on the use of yellow fever vaccines and vaccination published in
      2003. Footnotes to this paper provide a number of core references. In accordance
      with its mandate to provide guidance to Member States on health policy matters,
      WHO issues a series of regularly updated position papers on vaccines and
      combinations of vaccines against diseases that have an international public
      health impact. These papers are concerned primarily with the use of vaccines in
      large-scale immunization programmes; they summarize essential background
      information on diseases and vaccines, and conclude with WHO's current position on
      the use of vaccines in the global context. This paper reflects the
      recommendations of WHO's Strategic Advisory Group of Experts (SAGE) on
      immunization. These recommendations were discussed by SAGE at its April 2013
      meeting. Evidence presented at the meeting can be accessed at
      http://www.who.int/immunization/sage/previous/en/index.html.

PMID- 24852722
TI  - Causes of variation in BCG vaccine efficacy: examining evidence from the BCG
      REVAC cluster randomized trial to explore the masking and the blocking
      hypotheses.
AB  - BCG protection varies and in some places (nearest the equator) is low or absent.
      Understanding this variation can inform the efforts to develop new vaccines
      against tuberculosis. Two main hypotheses are used to explain this variation:
      under masking, new vaccines are unlikely to increase protection; under blocking
      new vaccines have a greater potential to be effective when BCG is not. We
      conducted a cluster randomized trial to explored the masking and blocking
      hypotheses by studying BCG vaccine efficacy of neonatal vaccination and when
      administered for the first or a second (revaccination) time at school age in two
      sites (Manaus close and Salvador further south from the equator). Seven hundred
      and sixty three state schools were matched on socio economic characteristics of
      the neighborhood and 239,934 children were randomized to vaccine (BCG vaccination
      at school age) or control group. Protection by first BCG vaccination at school
      age was high in Salvador (34%, 95% CI 7-53%, p=0.017) but low in Manaus (8%, 95%
      CI t0 39-40%, p=0.686). For revaccination at school age, protection was modest in
      Salvador (19%, 95% CI 3-33%, p=0.022) and absent in Manaus (1%, 95% CI to 27-23%,
      p=0.932). Vaccine efficacy for neonatal vaccination was similar in Salvador (40%,
      95% CI 22-54%, p<0.001) and Manaus (36%, 95% CI 11-53%, p=0.008). Variation in
      BCG efficacy was marked when vaccine was given at school age but absent at birth,
      which points towards blocking as the dominant mechanism. New tuberculosis
      vaccines that overcome or by pass this blocking effect could confer protection in
      situations where BCG is not protective.

PMID- 24852724
TI  - Isolation, identification, characterization, and evaluation of cadmium removal
      capacity of Enterobacter species.
AB  - This study focused on the isolation and characterization of high cadmium
      resistant bacterial strains, possible exploitation of its cadmium-accumulation
      and cadmium-induced proteins. Cadmium-resistant bacterial strains designated as
      RZ1 and RZ2 were isolated from industrial wastewater of Penang, Malaysia. These
      isolates were identified as Enterobacter mori and Enterobacter sp. WS12 on the
      basis of phenotypic, biochemical and 16S rDNA sequence based molecular
      phylogenetic characteristics. Both isolates were Gram negative, cocci, and
      growing well in Lauria-Bertani broth medium at 35  degrees C temperature and pH
      7.0. Results also indicated that Enterobacter mori and Enterobacter sp. WS12are
      capable to remove 87.75 and 85.11% of the cadmium from 100 ug ml(-1)
      concentration, respectively. This study indicates that these strains can be
      useful as an inexpensive and efficient bioremediation technology to remove and
      recover the cadmium from wastewater. 

PMID- 24852725
TI  - [Courses in microsurgical techniques in France and abroad].
AB  - The objective of this work was to determine the state of current training
      programs for microsurgery in France and abroad. Our survey of microsurgery
      training programs determined the registration volume, program contents, and
      number of students in France, and looked at registration volume and teaching time
      for programs abroad. Data were obtained from the Internet, university
      administration, those responsible for university diploma programs, and students.
      There were 18 university diploma programs in microsurgery in France. The average
      list price was ?1,129 for an average of 19 hours of theoretical training and 100
      hours of practice. Evaluation methods varied, but all required at least vascular
      anastomosis in rats. In 2011-2012, 148 students were enrolled and 126 graduated
      (85% passing rate). Abroad, 16 basic courses were listed in the USA, Europe and
      Asia. Nine advanced courses were offered. The average price was $1,346 for 36
      hours of practice in the basic courses and $1,955 for over 50 hours of training
      in advanced courses. None of these courses gave out a diploma. Our results show
      that in France, university diploma programs in microsurgery are heterogeneous and
      the French College should consider updating them. Globally, a study is underway
      by the International Microsurgical Simulation Society.

PMID- 24852723
TI  - Reconstructing the evolutionary origins and phylogeography of hantaviruses.
AB  - Rodents have long been recognized as the principal reservoirs of hantaviruses.
      However, with the discovery of genetically distinct and phylogenetically
      divergent lineages of hantaviruses in multiple species of shrews, moles, and
      insectivorous bats from widely separated geographic regions, a far more complex
      landscape of hantavirus host distribution, evolution, and phylogeography is
      emerging. Detailed phylogenetic analyses, based on partial and full-length
      genomes of previously described rodent-borne hantaviruses and newly detected non
      rodent-borne hantaviruses, indicate an Asian origin and support the emerging
      concept that ancestral non-rodent mammals may have served as the hosts of
      primordial hantaviruses. 

PMID- 24852727
TI  - Meta-analysis of anxiety disorders and temperament.
AB  - BACKGROUND: The aims of the present study were to explore whether symptoms in
      different anxiety disorders are associated with Cloninger's model temperament
      dimensions novelty seeking (NS), harm avoidance (HA), reward dependence and
      persistence compared with control subjects in clinical samples of adults or late
      adolescents. METHOD: Literature search in the following databases: Cochrane
      Library, PubMed (Medline), Web of Science, Psycinfo and PsycArticles. Systematic
      review, grading the level of evidence and meta-analysis for each disorder by
      comparing the temperament dimension scores between patient and control samples in
      single studies. RESULTS: A total of 40 papers fulfilled the inclusion criteria.
      Meta-analyses were conducted on a total of 24 studies focusing on panic disorder
      (PD), social anxiety disorder (SAD) and obsessive-compulsive disorder (OCD). The
      primary finding was a constant and clinically marked positive association between
      the HA temperament dimension and symptoms of PD, SAD and OCD, with a most marked
      effect in SAD, and a moderate effect in OCD and PD. Second, less marked and
      clinically marginal associations between NS score and SAD and OCD (negative
      associations), but no associations with PD were observed. The meta-analyses
      revealed heterogeneity between the results of individual studies, especially in
      the analyses including SAD and OCD. CONCLUSIONS: PD, SAD and OCD share a marked
      and state-dependent avoidant behavioral pattern, which is common for all anxiety
      disorders. However, PD showed a different pattern of arousal to novel stimuli
      from that of SAD and OCD. The findings are state dependent and based on cross
      sectional studies.

PMID- 24852726
TI  - Evidence-based guidelines of the spanish psoriasis group on the use of biologic
      therapy in patients with psoriasis in difficult-to-treat sites (nails, scalp,
      palms, and soles).
AB  - Psoriatic lesions affecting the scalp, nails, palms, and the soles of the feet
      are described as difficult-to-treat psoriasis and require specific management.
      Involvement of these sites often has a significant physical and emotional impact
      on the patient and the lesions are difficult to control with topical treatments
      owing to inadequate penetration of active ingredients and the poor cosmetic
      characteristics of the vehicles used. Consequently, when difficult-to-treat sites
      are involved, psoriasis can be considered severe even though the lesions are not
      extensive. Scant information is available about the use of biologic therapy in
      this setting, and published data generally comes from clinical trials of patients
      who also had moderate to severe extensive lesions or from small case series and
      isolated case reports. In this article we review the quality of the scientific
      evidence for the 4 biologic agents currently available in Spain (infliximab,
      etanercept, adalimumab, and ustekinumab) and report level i evidence for the use
      of biologics to treat nail psoriasis (level of recommendation A) and a somewhat
      lower level of evidence in the case of scalp involvement and palmoplantar
      psoriasis. 

PMID- 24852728
TI  - Transforming doctoral education through the clinical electronic portfolio.
AB  - The DNP is a terminal degree focusing on the preparation of expert clinicians
      with advanced leadership, evidence-based practice, and systems management skills.
      An electronic clinical portfolio (e-portfolio) allows students to showcase their
      individual experiences, provides an objective measure of their achievement, and
      demonstrates integration of the core doctoral competencies within each specialty.
      The purpose of this article was to describe the development of an e-portfolio and
      provide general guidelines for successful implementation and evaluation. 

PMID- 24852730
TI  - Effect of precursor stoichiometry on the morphology of nanoporous platinum
      sponges.
AB  - Nanoscale sponges formed by de-alloying suitable metallic alloys have a wide
      variety of potential applications due to their enhanced catalytic, optical, and
      electrochemical properties. In general, these materials have a bi-continuous,
      vermicular morphology of pores and ligaments with a fibrous appearance; however,
      other morphologies are sometimes reported. Here, we investigate how stoichiometry
      and process parameters control the characteristics of sponges formed from thin
      film precursors of AlxPt. Materials deposited at elevated temperatures and with
      mole fraction of Al between 0.65 and 0.90 produce the classic isotropic fibrous
      sponges with a morphology that varies systematically with precursor
      stoichiometry; however, de-alloying of material deposited at room temperature
      produced unusual isotropic foamy sponges. The evidence suggests that formation of
      a conventional fibrous sponge requires an equilibrated precursor whereas foamy
      morphologies will result if the precursor is metastable. Modeling was used to
      investigate the range of possible morphologies. As stoichiometry changed in the
      model system, the average mean and Gaussian curvature of the sponges
      systematically changed, too. The evolution of these shapes passed through certain
      special morphologies; for example, modelled structures with 0.80 Al had a zero
      average Gaussian curvature and might represent a structural optimum for some
      applications. These observations provide a means to control sponge morphology at
      the nanoscale. 

PMID- 24852729
TI  - Multi-parameter assessment of platelet inhibition and its stability during
      aspirin and clopidogrel therapy.
AB  - INTRODUCTION: Poor response to antiplatelet drugs is associated with adverse
      outcomes. We assessed platelet inhibition and its stability and tested
      correlation and agreement between platelet function assays. METHODS: Peripheral
      blood from 58 patients on both aspirin and clopidogrel who underwent percutaneous
      coronary intervention (PCI) was collected at hospital discharge (visit-1) and at
      30-90 days (visit-2). Platelet function was measured using light transmission
      aggregometry (LTA-AA and LTA-ADP), VerifyNow(r) (Aspirin; ARU and P2Y12; PRU), ex
      vivo TxB2, urinary 11dhTxB2, and VASP (PRI) assays. Data were analyzed as
      continuous, quartiles and binary. Patients were defined as aspirin poor responder
      (PR) with ARU >= 550, LTA-AA maximum >= 20%, TxB2 >= 1 ng/mL or 11dhTxB2 >= 1,500
      pg/mg of creatinine and as clopidogrel PR with PRU >= 240, PRU >= 208, LTA-ADP
      maximum >= 40%, PRI >= 50%, or PRI >=66%. RESULTS: Aspirin PR was 3-33% and
      clopidogrel PR was 10-35% in visit-1. LTA-AA, 11dhTxB2, and all clopidogrel
      response measures showed correlation and agreement between visit-1 and visit-2.
      The highest agreement between two visits was revealed by PRU >= 240 and PRI >=
      66% (PRU-kappa=0.7, 95% CI=0.47, 0.93; PRI-kappa=0.69, 95% CI=0.42, 0.95, p
      values<0.001). Comparison of platelet function assays in a single visit (visit-1)
      revealed a poor correlation between LTA-AA and 11dhTxB2 assays and no agreement
      among aspirin-response assays. The highest correlation and agreement were
      obtained between VerifyNow(r) P2Y12 and VASP assays (rho=0.7, p-value<0.001 and
      PRU >= 208-PRI-kappa=0.41-0.42, 95% CI=0.13, 0.69, p-values<0.001). CONCLUSIONS:
      Platelet inhibition is stable during aspirin and clopidogrel treatment.
      Clopidogrel-response assays correlate and agree with each other better than
      aspirin-response assays.

PMID- 24852731
TI  - Coeliac disease in the oral mucosa?

PMID- 24852732
TI  - An economic analysis of inadequate prescription of antiulcer medications for in
      hospital patients at a third level institution in Colombia.
AB  - INTRODUCTION: The prescription and costs of antiulcer medications for in-hospital
      use have increased during recent years with reported inadequate use and
      underused. AIM: To determine the patterns of prescription-indication and also
      perform an economic analysis of the overcost caused by the non-justified use of
      antiulcer medications in a third level hospital in Colombia. MATERIALS AND
      METHODS: Cross-sectional study of prescription-indication of antiulcer
      medications for patients hospitalized in "Hospital Universitario San Jorge" of
      Pereira during July of 2012. Adequate or inadequate prescription of the first
      antiulcer medication prescribed was determined as well as for others prescribed
      during the hospital stay, supported by clinical practice guidelines from the
      Zaragoza I sector workgroup, clinical guidelines from the Australian Health
      Department, and finally the American College of Gastroenterology Criteria for
      stress ulcer prophylaxis. Daily defined dose per bed/day was used, as well as the
      cost for 100 beds/day and the cost of each bed/drug. A multivariate analysis was
      carried out using SPSS 21.0. RESULTS: 778 patients were analyzed, 435 men (55.9
      %) and 343 women, mean age 56.6 +/- 20.1 years. The number of patients without
      justification for the prescription of the first antiulcer medication was 377
      (48.5 %), and during the whole in-hospital time it was 336 (43.2 %). Ranitidine
      was the most used medication, in 438 patients (56.3 %). The cost/month for poorly
      justified antiulcer medications was ? 3,335.6. The annual estimated cost for
      inadequate prescriptions of antiulcer medications was ? 16,770.0 per 100 beds.
      CONCLUSION: A lower inadequate prescription rate of antiulcer medications was
      identified compared with other studies; however it was still high and is
      troubling because of the major costs that these inadequate prescriptions
      generates for the institution.

PMID- 24852733
TI  - Histopathological findings in the oral mucosa of celiac patients.
AB  - BACKGROUND: Celiac disease (CD) is an immune-mediated enteropathy triggered by
      the ingestion of gluten in genetically susceptible subjects. Although the small
      intestinal mucosa is the main site of the gut's involvement in CD, other mucosal
      surfaces belonging to the gastrointestinal tract and the gut-associated lymphoid
      tissue are known to be affected. AIM: Assuming that the oral mucosa could reflect
      the histopathological inflammatory alterations of the intestine in CD patients,
      this study wishes to assess the pattern of T-cell subsets in the oral mucosa of
      young adults with CD. METHODS: A group of 37 patients (age range 20-38 years;
      female: male ratio 28:9) with CD were enrolled. Out of 37 patients, 19 patients
      (group A) followed a gluten free diet (GFD) -2 patients from less than one year;
      6 patients between 1 and 5 years; 11 patients more than 5 years- while 18
      patients (group B) were still untreated. Fifteen healthy volunteers (age range 18
      35 years, female: Male ratio 11:4) served as controls for the CD patients.
      Ethical approval for the research was granted by the Ethics Committee. Biopsy
      specimens were taken from normal looking oral mucosa. The immunohistochemical
      investigation was performed with monoclonal antibodies to CD3, CD4, CD8, and
      gamma/delta-chains T cell receptor (TCR). RESULTS: The T-lymphocytic inflammatory
      infiltrate was significantly (p < 0.0001) increased in group B (both compared
      with group A and with the control group). CONCLUSION: This study confirms the
      oral cavity to be a site of involvement of CD and its possible diagnostic
      potentiality in this disease.

PMID- 24852735
TI  - Experimental study of hybrid-knife endoscopic submucosal dissection (ESD) versus
      standard ESD in a Western country.
AB  - BACKGROUND: Endoscopic submucosal dissection (ESD) is an effective but time
      consuming treatment for early neoplasia that requires a high level of expertise.
      OBJECTIVE: The objective of this study was to assess the efficacy and learning
      curve of gastric ESD with a hybrid knife with high pressure water jet and to
      compare with standard ESD. MATERIAL AND METHODS: We performed a prospective non
      survival animal study comparing hybrid-knife and standard gastric ESD. Variables
      recorded were: Number of en-bloc ESD, number of ESD with all marks included (R0),
      size of specimens, time and speed of dissection and adverse events. Ten
      endoscopists performed a total of 50 gastric ESD (30 hybrid-knife and 20
      standard). RESULTS: Forty-six (92 %) ESD were en-bloc and 25 (50 %) R0 (hybrid
      knife: n = 13, 44 %; standard: n = 16, 80 %; p = 0.04). Hybrid-knife ESD was
      faster than standard (time: 44.6 +/- 21.4 minutes vs. 68.7 +/- 33.5 minutes; p =
      0.009 and velocity: 20.8 +/- 9.2 mm(2)/min vs. 14.3 +/- 9.3 mm(2)/min (p =
      0.079). Adverse events were not different. There was no change in speed with any
      of two techniques (hybrid-knife: From 20.33 +/- 15.68 to 28.18 +/- 20.07
      mm(2)/min; p = 0.615 and standard: From 6.4 +/- 0.3 to 19.48 +/- 19.21 mm(2)/min;
      p = 0.607). The learning curve showed a significant improvement in R0 rate in the
      hybrid-knife group (from 30 % to 100 %). CONCLUSION: despite the initial
      performance of hybrid-knife ESD is worse than standard ESD, the learning curve
      with hybrid knife ESD is short and is associated with a rapid improvement. The
      introduction of new tools to facilitate ESD should be implemented with caution in
      order to avoid a negative impact on the results.

PMID- 24852734
TI  - Dental erosion, an extraesophageal manifestation of gastroesophageal reflux
      disease. The experience of a center for digestive physiology in Southeastern
      Mexico.
AB  - BACKGROUND: Dental erosion (DE) is the loss of the hard tissues of the tooth
      produced by the action of gastric juice, pepsin and acid on the dental enamel,
      its frequency ranges from 5 to 53.41 %. In Mexico there are no reports on the
      frequency and possible association. OBJECTIVE: To establish the prevalence of
      dental erosion and its relationship to GERD. PATIENTS AND METHODS: Prospective,
      observational, descriptive and comparative study was conducted in 60 patients
      diagnosed with GERD and 60 healthy patients at the Institute of Medical and
      Biological Research of the Universidad Veracruzana in Veracruz city.
      Anthropometric characteristics, dietary habits, oral hygiene, alcohol
      consumption, smoking, ED index and Index of decayed/missing dental pieces/sealed
      and correlation between severity of ED and GERD were analyzed. RESULTS: 78.67 %
      of patients with GERD had ED, 23.33 % corresponded to grade 0, 41.67 % to N1, N2
      and 23.33 % to 11.67 % to N3. Predominance of females (2,3:1). The mean age was
      50.92 +/- 13.52 years. The severity of dental erosion was significantly related
      to the severity of reflux, halitosis, CPO index and poor eating habits. There was
      no statistically significant difference in the other variables analyzed.
      CONCLUSIONS: Dental erosion has a high frequency in patients with GERD and reflux
      characteristics are directly related to their severity and therefore should be
      considered as a manifestation of GERD extraesophageal.

PMID- 24852736
TI  - Endoscopic diagnosis and therapies for Barrett esophagus. A review.
AB  - Barrett's esophagus is an area of great interest in Gastroenterology, with an
      increasing number of research studies being published in recent years and
      decades. Due to the fast growing evidence regarding this disease, it has become
      extremely difficult to keep updated on this subject. The present review article
      aims to summarize and update what is known regarding diagnosis and therapy in
      Barrett's esophagus. A critical and detailed review is made and the role of
      surveillance for this condition, techniques available for diagnosis (standard
      white light endoscopy, virtual chromoendoscopy, magnification...) and treatment
      (mucosectomy, ablation...) are presented. New and emerging technologies are
      described in detail and existing evidence is presented.

PMID- 24852737
TI  - Endoscopic submucosal dissection. Sociedad Espanola de Endoscopia Digestiva
      (SEED) clinical guideline.

PMID- 24852739
TI  - Mechanical colonic obstruction due to diaphragmatic hernia. Report of a case.

PMID- 24852738
TI  - Diffuse colon opacifications due to lanthanum carbonate.

PMID- 24852740
TI  - Transoral endoluminal approach to Zenker's diverticulum using LigasureTM. Early
      clinical experience.
AB  - The development of minimally invasive procedures has rekindled interest in
      endoluminal techniques for the management of Zenker's diverticulum. Tissue
      sealers as employed in laparoscopic surgery have not been previously used for
      Zenker's diverticulum septotomy.Supported by the established safety of linear
      cutters, bipolar forceps, and ultrasonic scalpels, we have started a procedure
      using the Ligasure 5TM tissue sealer. Safety and efficacy results in our early
      clinical experience are shown for a prospective series of 5 consecutive Zenker's
      diverticulum cases that were perorally managed with tissue sealing.The procedure
      was quickly and safely performed in the endoscopy room under sedation. Mean
      number of seals per patient was 2, and mean procedure duration was 33 minutes. No
      complications developed during or after the procedure, and patients were
      discharged with immediate dysphagia relief and adequate oral tolerance. No
      diverticular relapses occurred after a mean follow-up of 21 months (range 18-30).
      This procedure may be repeated as often as desired with no need for hospital
      admission. Safety should be prospectively assessed by further studies using a
      higher number of procedures.

PMID- 24852741
TI  - Severe spruelike enteropathy due to olmesartan.
AB  - Villous atrophy and negative serologic testing is a diagnostic challenge, and the
      rarer possibility of drug-induced enteritis should be considered. We report a
      rare case of severe spruelike enteritis due to olmesartan that completely
      resolved after withdrawal of the drug. The possibility that patient labeled as
      "refractory" celiac disease may actually be due to drug treatment should always
      be taken into consideration, to avoid unnecessary investigations.

PMID- 24852742
TI  - [Non cirrhotic portal hypertension].

PMID- 24852743
TI  - Acute pancreatitis as fatal complication after chemoembolization of
      hepatocellular carcinoma.

PMID- 24852744
TI  - Acute necrotizing pancreatitis after transarterial chemoembolization of
      hepatocellular carcinoma: An unusual complication.

PMID- 24852745
TI  - Ectopic hepatocellular carcinoma in the gallbladder.

PMID- 24852746
TI  - Ulcerative colitis and isotretinoin: Is there a causal relationship?

PMID- 24852747
TI  - Conservative management of isolated dissection of the superior mesenteric artery.

PMID- 24852748
TI  - Cell-based modulation of autoimmune responses in multiple sclerosis and
      experimental autoimmmune encephalomyelitis: therapeutic implications.
AB  - Multiple sclerosis (MS) is a prototypic autoimmune inflammatory disorder of the
      central nervous system (CNS). MS pathogenesis is a complex phenomenon that is
      influenced by genetic and environmental factors that lead to the dysregulation of
      immune homeostasis and tolerance. It has been shown that pathogenic T lymphocyte
      subsets, such as T helper 1 (Th1) and Th17 cells, play a crucial role in the
      autoimmune cascade influencing disease initiation, progression and subsequent
      tissue damage during MS. On the other hand, several mechanisms have been
      described in both patients and animal models of MS with the potential to modulate
      myelin-specific autoimmune responses and to facilitate amelioration of disease
      pathology. To this end, regulatory T cells (Tregs) are considered to be a
      powerful cell subset not only in the maintenance of homeostasis but also in the
      re-establishment of tolerance. Along these lines, other cell subsets such as
      dendritic cells (DCs), myeloid-derived suppressor cells (MDSCs), gammadelta T
      cells and natural killer (NK) cells have been shown to regulate the autoimmune
      response in the CNS under certain circumstances. This review will attempt to
      summarize the relevant knowledge of the regulatory mechanisms exerted by immune
      cells in MS that could hold the promise for the design of novel therapeutic
      strategies.

PMID- 24852750
TI  - High concentrate-induced subacute ruminal acidosis (SARA) increases plasma acute
      phase proteins (APPs) and cortisol in goats.
AB  - The aim of this study was to investigate changes of stress status in dairy goats
      induced to subacute ruminal acidosis (SARA). The level of acute phase proteins
      (APPs) including haptoglobin (HP) and serum amyloid A (SAA) in plasma and their
      mRNA expression in liver, as well as plasma cortisol and genes expression of key
      factors controlling cortisol synthesis in adrenal cortex were compared between
      SARA and control goats. SARA was induced by feeding high concentrate diet (60%
      concentrate of dry matter) for 3 weeks (SARA, n=6), while control goats (Con,
      n=6) received a low concentrate diet (40% concentrate of dry matter) during the
      experimental time. SARA goats showed ruminal pH below 5.8 for more than 3 h per
      day, which was significantly lower than control goats (pH>6.0). SARA goats
      demonstrated a significant increase of hepatic HP and SAA mRNA expression
      (P<0.05), and the level of HP but not SAA in plasma was markedly increased
      compared with control (P<0.05). The level of cortisol in plasma showed a trend to
      increase in SARA goats (0.05<P<0.1). In adrenal cortex, mRNA expression of
      17alpha-hydroxylase cytochrome (P45017alpha ) (P<0.01) and 3beta-hydroxysteroid
      dehydrogenase (3beta-HSD) (P<0.05) was significantly increased in SARA goats. The
      contents of 3beta-HSD and P450 side-chain cleavage protein were increased by
      58.6% and 39.4%, respectively, but did not reach the statistical significance
      (P>0.05). These results suggested that SARA goats experienced a certain stress
      status, exhibiting an increase in HP production and cortisol secretion. 

PMID- 24852749
TI  - Genotoxic Klebsiella pneumoniae in Taiwan.
AB  - BACKGROUND: Colibactin is a nonribosomal peptide-polyketide synthesized by multi
      enzyme complexes encoded by the pks gene cluster. Colibactin-producing
      Escherichia coli have been demonstrated to induce host DNA damage and promote
      colorectal cancer (CRC) development. In Taiwan, the occurrence of pyogenic liver
      abscess (PLA) has been suggested to correlate with an increasing risk of CRC, and
      Klebsiella pneumoniae is the predominant PLA pathogen in Taiwan.
      METHODOLOGY/PRINCIPAL FINDINGS: At the asn tRNA loci of the newly sequenced K.
      pneumoniae 1084 genome, we identified a 208-kb genomic island, KPHPI208, of which
      a module identical to the E. coli pks colibactin gene cluster was recognized.
      KPHPI208 consists of eight modules, including the colibactin module and the
      modules predicted to be involved in integration, conjugation, yersiniabactin
      production, microcin production, and unknown functions. Transient infection of
      BALB/c normal liver cells with K. pneumoniae 1084 increased the phosphorylation
      of histone H2AX, indicating the induction of host DNA damage. Colibactin was
      required for the genotoxicity of K. pneumoniae 1084, as it was diminished by
      deletion of clbA gene and restored to the wild type level by trans
      complementation with a clbA coding plasmid. Besides, BALB/c mice infected with K.
      pneumoniae 1084 exhibited enhanced DNA damage in the liver parenchymal cells when
      compared to the isogenic clbA deletion mutant. By PCR detection, the prevalence
      of pks-positive K. pneumoniae in Taiwan is 25.6%, which is higher than that
      reported in Europe (3.5%), and is significantly correlated with K1 type, which
      predominantly accounted for PLA in Taiwan. CONCLUSIONS: Our knowledge regarding
      how bacteria contribute to carcinogenesis has just begun. The identification of
      genotoxic K. pneumoniae and its genetic components will facilitate future studies
      to elucidate the molecular basis underlying the link between K. pneumoniae, PLA,
      and CRC.

PMID- 24852751
TI  - Lay beliefs about autism spectrum disorder among the general public and childcare
      providers.
AB  - We conducted a survey of beliefs about autism among the general public in the
      United States and Canada (n = 823) and among individuals working in childcare
      facilities in the state of Idaho (n = 176). Results included the following.
      Almost all respondents correctly believed that autism's primary causes are
      genetic and neurological (not parenting, drugs, or current diet), that it can be
      identified in early childhood, and that helpful interventions exist. Respondents
      generally distinguished diagnostic from non-diagnostic traits, but approximately
      half incorrectly labeled constant squirming as diagnostic and difficulties in
      making friends as non-diagnostic. College graduates and childcare workers were
      more likely to have learned about autism in professional/academic settings and to
      correctly recognize diagnostic traits. Of concern, 10% of respondents considered
      vaccinations to be among the two main causes of autism. Accurate public
      understanding of autism spectrum disorders can facilitate early identification
      and effective intervention; our results suggest that efficient channels for
      conveying accurate information include broadcast and online media (from which the
      general public, especially members of ethnic minority groups, were most likely to
      learn about autism), and professional development courses for childcare
      providers. 

PMID- 24852752
TI  - Emotion recognition from congruent and incongruent emotional expressions and
      situational cues in children with autism spectrum disorder.
AB  - In this research, the emotion recognition abilities of children with autism
      spectrum disorder and typically developing children were compared. When facial
      expressions and situational cues of emotion were congruent, accuracy in
      recognizing emotions was good for both children with autism spectrum disorder and
      typically developing children. When presented with facial expressions incongruent
      with situational cues, children with autism spectrum disorder relied more on
      facial cues than situational cues, whereas typically developing children relied
      more on situational cues. The exception was fear. When presented with incongruent
      information (i.e. a smiling boy surrounded by a swarm of bees), most children
      based their response on the situation and indicated that the boy felt scared.
      While the majority of typically developing children commented on the disparity
      between facial expressions and situational cues, children with autism spectrum
      disorder did not mention the conflicting cues. Although typically developing
      children were more accurate in recognizing emotion with situational cues,
      children with autism spectrum disorder were still adequate at identifying emotion
      from situational cues alone. These findings suggest that children with autism
      spectrum disorder show an understanding of simple emotions in prototypical
      situations, but may prefer facial expressions when facial expressions and
      situational cues are incongruent. Reasons for these findings are discussed. 

PMID- 24852753
TI  - Chronic ethanol consumption increases myocardial mitochondrial DNA mutations: a
      potential contribution by mitochondrial topoisomerases.
AB  - AIMS: Alcoholic cardiomyopathy (ACM) presents as decreased myocardial
      contractility, arrhythmias and secondary non-ischemic dilated cardiomyopathy
      leading to heart failure. Mitochondrial dysfunction is known to have a
      significant role in the development and complications of ACM. This study
      investigated if chronic ethanol feeding promoted myocardial mitochondrial
      topoisomerase dysfunction as one underlying cause of mitochondrial DNA (mtDNA)
      damage and mitochondrial dysfunction in ACM. METHODS: The impact of chronic
      ethanol exposure on the myocardial mitochondria was examined in both neonatal
      cardiomyocytes using 50 mM ethanol for 6 days and in rats assigned to control or
      ethanol feeding groups for 4 months. RESULTS: Chronic ethanol feeding led to
      significant (P < 0.05) decreases in M-mode Fractional Shortening, ejection
      fraction, and the cardiac output index as well as increases in Tau. Ethanol
      feeding promoted mitochondrial dysfunction as evidenced by significantly
      decreased left ventricle cytochrome oxidase activity and decreases in
      mitochondrial protein content. Both in rats and in cultured cardiomyocytes,
      chronic ethanol presentation significantly increased mtDNA damage. Using isolated
      myocardial mitochondria, both mitochondrial topoisomerase-dependent DNA cleavage
      and DNA relaxation were significantly altered by ethanol feeding. CONCLUSION:
      Chronic ethanol feeding compromised cardiovascular and mitochondrial function as
      a result of a decline in mtDNA integrity that was in part the consequence of
      mitochondrial topoisomerase dysfunction. Understanding the regulation of the
      mitochondrial topoisomerases is critical for protection of mtDNA, not only for
      the management of alcoholic cardiomyopathy, but also for the many other clinical
      treatments that targets the topoisomerases in the alcoholic patient.

PMID- 24852754
TI  - Prostacyclin analogue beraprost inhibits cardiac fibroblast proliferation
      depending on prostacyclin receptor activation through a TGF beta-Smad signal
      pathway.
AB  - Previous studies showed that prostacyclin inhibited fibrosis. However, both
      receptors of prostacyclin, prostacyclin receptor (IP) and peroxisome proliferator
      activated receptor (PPAR), are abundant in cardiac fibroblasts. Here we
      investigated which receptor was vital in the anti-fibrosis effect of
      prostacyclin. In addition, the possible mechanism involved in protective effects
      of prostacyclin against cardiac fibrosis was also studied. We found that
      beraprost, a prostacyclin analogue, inhibited angiotensin II (Ang II)-induced
      neonatal rat cardiac fibroblast proliferation in a concentration-dependent and
      time-dependent manner. Beraprost also suppressed Ang II-induced collagen I mRNA
      expression and protein synthesis in cardiac fibroblasts. After IP expression was
      knocked down by siRNA, Ang II-induced proliferation and collagen I synthesis
      could no longer be rescued by beraprost. However, treating cells with different
      specific inhibitors of PPAR subtypes prior to beraprost and Ang II stimulation,
      all of the above attenuating effects of beraprost were still available. Moreover,
      beraprost significantly blocked transforming growth factor beta (TGF beta)
      expression as well as Smad2 phosphorylation and reduced Smad-DNA binding
      activity. Beraprost also increased phosphorylation of cAMP response element
      binding protein (CREB) at Ser133 in the nucleus. Co-immunoprecipitation analysis
      revealed that beraprost increased CREB but decreased Smad2 binding to CREB
      binding protein (CBP) in nucleus. In conclusion, beraprost inhibits cardiac
      fibroblast proliferation by activating IP and suppressing TGF beta-Smad signal
      pathway. 

PMID- 24852755
TI  - 3-Deazaneplanocin A (DZNep), an inhibitor of the histone methyltransferase EZH2,
      induces apoptosis and reduces cell migration in chondrosarcoma cells.
AB  - OBJECTIVE: Growing evidences indicate that the histone methyltransferase EZH2
      (enhancer of zeste homolog 2) may be an appropriate therapeutic target in some
      tumors. Indeed, a high expression of EZH2 is correlated with poor prognosis and
      metastasis in many cancers. In addition, 3-Deazaneplanocin A (DZNep), an S
      adenosyl-L homocysteine hydrolase inhibitor which induces EZH2 protein depletion,
      leads to cell death in several cancers and tumors. The aim of this study was to
      determine whether an epigenetic therapy targeting EZH2 with DZNep may be also
      efficient to treat chondrosarcomas. METHODS: EZH2 expression was determined by
      immunohistochemistry and western-blot. Chondrosarcoma cell line CH2879 was
      cultured in the presence of DZNep, and its growth and survival were evaluated by
      counting adherent cells periodically. Apoptosis was assayed by cell cycle
      analysis, Apo2.7 expression using flow cytometry, and by PARP cleavage using
      western-blot. Cell migration was assessed by wound healing assay. RESULTS:
      Chondrosarcomas (at least with high grade) highly express EZH2, at contrary to
      enchondromas or chondrocytes. In vitro, DZNep inhibits EZH2 protein expression,
      and subsequently reduces the trimethylation of lysine 27 on histone H3
      (H3K27me3). Interestingly, DZNep induces cell death of chondrosarcoma cell lines
      by apoptosis, while it slightly reduces growth of normal chondrocytes. In
      addition, DZNep reduces cell migration. CONCLUSION: These results indicate that
      an epigenetic therapy that pharmacologically targets EZH2 via DZNep may
      constitute a novel approach to treat chondrosarcomas.

PMID- 24852756
TI  - A double-blind, placebo-controlled, randomised, clinical study on the
      effectiveness of collagen peptide on osteoarthritis.
AB  - BACKGROUND: Recent studies show that enzymatically hydrolysed collagen, the
      collagen peptide, is absorbed and distributed to joint tissues and has analgesic
      and anti-inflammatory properties. A double-blind, placebo-controlled, randomised
      trial with collagen peptides isolated from pork skin (PCP) and bovine bone (BCP)
      sources was carried out to study the effectiveness of orally supplemented
      collagen peptide to control the progression of osteoarthritis in patients
      diagnosed with knee osteoarthritis. Improvement in treatment was assessed with
      reduction in Western Ontario McMaster Universities (WOMAC), visual analogue scale
      (VAS) and quality of life (QOL) scores from baseline to 13 weeks (Visit 7).
      Safety and tolerability were also evaluated. RESULTS: There was significant
      reduction from baseline to Visit 7 in the primary end points of WOMAC and VAS
      scores and in the secondary end point of QOL score in subjects with PCP and BCP
      groups, while in subjects with placebo group the end point indices remained
      unaltered. Furthermore, all the score levels of WOMAC, VAS and QOL decreased
      significantly (P < 0.01) in the study group compared to placebo group in Visit 7.
      CONCLUSION: The study demonstrated that collagen peptides are potential
      therapeutic agents as nutritional supplements for the management of
      osteoarthritis and maintenance of joint health.

PMID- 24852757
TI  - Effects of prenatal cocaine exposure on social development in mice.
AB  - Prenatal cocaine exposure (PCE) in humans and animals has been shown to impair
      social development. Molecules that mediate synaptic plasticity and learning in
      the medial prefrontal cortex (mPFC), specifically brain-derived neurotrophic
      factor (BDNF) and its downstream signaling molecule, early growth response
      protein 1 (egr1), have been shown to affect the regulation of social interactions
      (SI). In this study we determined the effects of PCE on SI and the corresponding
      ultrasonic vocalizations (USVs) in developing mice. Furthermore, we studied the
      PCE-induced changes in the constitutive expression of BDNF, egr1 and their
      transcriptional regulators in the mPFC as a possible molecular mechanism
      mediating the altered SI. In prenatal cocaine-exposed (PCOC) mice we identified
      increased SI and USV production at postnatal day (PD) 25, and increased SI but
      not USVs at PD35. By PD45 the expression of both social behaviors normalized in
      PCOC mice. At the molecular level, we found increased BDNF exon IV and egr1 mRNA
      in the mPFC of PCOC mice at PD30 that normalized by PD45. This was concurrent
      with increased EGR1 protein in the mPFC of PCOC mice at PD30, suggesting a role
      of egr1 in the enhanced SI observed in juvenile PCOC mice. Additionally, by
      measuring the association of acetylation of histone 3 at lysine residues 9 and 14
      (acH3K9,14) and MeCP2 at the promoters of BDNF exons I and IV and egr1, our
      results provide evidence of promoter-specific alterations in the mPFC of PCOC
      juvenile mice, with increased association of acH3K9,14 only at the BDNF exon IV
      promoter. These results identify a potential PCE-induced molecular alteration as
      the underlying neurobiological mechanism mediating the altered social development
      in juvenile mice.

PMID- 24852758
TI  - Rab35 is translocated from Arf6-positive perinuclear recycling endosomes to
      neurite tips during neurite outgrowth.
AB  - Small GTPase Rab35 is a key regulator of neurite outgrowth, and its activation
      dramatically enhances nerve growth factor (NGF)-induced neurite outgrowth. We
      recently reported finding that Rab35 and its effector molecules recruit EHD1, a
      facilitator of vesicle formation, to Arf6-positive perinuclear recycling
      endosomes (hereafter simply referred to as recycling endosomes) in response to
      NGF stimulation. Although Rab35 is likely to promote the formation of transport
      vesicles from recycling endosomes that contributes to neurite outgrowth, the
      destination of the vesicles during neurite outgrowth remains unknown. Here we
      report finding that Rab35 is translocated from recycling endosomes to neurite
      tips in a late phase of NGF stimulation. We found that Rab35 immunofluorescence
      signals accumulated at recycling endosomes during the first 6 h, i.e., the early
      phase of NGF stimulation and then translocated to neurite tips during the late
      phase of NGF stimulation (i.e., >6 h to <36 h after NGF stimulation). These
      findings suggest that Rab35 regulates membrane trafficking from recycling
      endosomes to neurite tips during neurite outgrowth.

PMID- 24852759
TI  - Use of segregation indices, Townsend Index, and air toxics data to assess
      lifetime cancer risk disparities in metropolitan Charleston, South Carolina, USA.
AB  - BACKGROUND: Studies have demonstrated a relationship between segregation and
      level of education, occupational opportunities, and risk behaviors, yet a paucity
      of research has elucidated the association between racial residential
      segregation, socioeconomic deprivation, and lifetime cancer risk. OBJECTIVES: We
      examined estimated lifetime cancer risk from air toxics by racial composition,
      segregation, and deprivation in census tracts in Metropolitan Charleston.
      METHODS: Segregation indices were used to measure the distribution of groups of
      people from different races within neighborhoods. The Townsend Index was used to
      measure economic deprivation in the study area. Poisson multivariate regressions
      were applied to assess the association of lifetime cancer risk with segregation
      indices and Townsend Index along with several sociodemographic measures. RESULTS:
      Lifetime cancer risk from all pollution sources was 28 persons/million for half
      of the census tracts in Metropolitan Charleston. Isolation Index and Townsend
      Index both showed significant correlation with lifetime cancer risk from
      different sources. This significance still holds after adjusting for other
      sociodemographic measures in a Poisson regression, and these two indices have
      stronger effect on lifetime cancer risk compared to the effects of
      sociodemographic measures. CONCLUSIONS: We found that material deprivation,
      measured by the Townsend Index and segregation measured by the Isolation index,
      introduced high impact on lifetime cancer risk by air toxics at the census tract
      level.

PMID- 24852760
TI  - Work history and mortality risks in 90,268 US radiological technologists.
AB  - OBJECTIVES: There have been few studies of work history and mortality risks in
      medical radiation workers. We expanded by 11 years and more outcomes our previous
      study of mortality risks and work history, a proxy for radiation exposure.
      METHODS: Using Cox proportional hazards models, we estimated mortality risks
      according to questionnaire work history responses from 1983 to 1989 through 2008
      by 90,268 US radiological technologists. We controlled for potential confounding
      by age, birth year, smoking history, body mass index, race and gender. RESULTS:
      There were 9566 deaths (3329 cancer and 3020 circulatory system diseases).
      Mortality risks increased significantly with earlier year began working for
      female breast (p trend=0.01) and stomach cancers (p trend=0.01), ischaemic heart
      (p trend=0.03) and cerebrovascular diseases (p trend=0.02). The significant trend
      with earlier year first worked was strongly apparent for breast cancer during
      baseline through 1997, but not 1998-2008. Risks were similar in the two periods
      for circulatory diseases. Radiological technologists working >=5 years before
      1950 had elevated mortality from breast cancer (HR=2.05, 95% CI 1.27 to 3.32),
      leukaemia (HR=2.57, 95% CI 0.96 to 6.68), ischaemic heart disease (HR=1.13, 95%
      CI 0.96 to 1.33) and cerebrovascular disease (HR=1.28, 95% CI 0.97 to 1.69). No
      other work history factors were consistently associated with mortality risks from
      specific cancers or circulatory diseases, or other conditions. CONCLUSIONS:
      Radiological technologists who began working in early periods and for more years
      before 1950 had increased mortality from a few cancers and some circulatory
      system diseases, likely reflecting higher occupational radiation exposures in the
      earlier years.

PMID- 24852761
TI  - The Clinical Outcomes of Immediate Versus Delayed Restoration Procedures on
      Immediate Implants: A Comparative Cohort Study for Single-Tooth Replacement.
AB  - BACKGROUND: Immediate implant placement into fresh extraction sockets is
      generally considered a reliable procedure that offers several clinical
      advantages. PURPOSE: The primary aim of this study was to evaluate and compare
      the overall clinical outcomes of immediate and delayed restoration procedures for
      implants placed in fresh extraction sockets by means of a flapless technique and
      resorbable membrane stabilizing a xenograft. Total costs and operating times were
      also compared. MATERIALS AND METHODS: In this prospective cohort study, changes
      of marginal bone level, facial soft tissue (DeltaFST), and width of keratinized
      gingiva (DeltaWKG), in addition to the papilla index, underwent a pairwise
      comparison; correlations with pristine buccal bone thickness were also
      investigated. RESULTS: Although similar results were recorded for the two
      procedures, with a bone loss of -1.0 +/- 0.5 mm and -0.9 +/- 0.7 mm,
      respectively, for immediate and delayed restoration, negative remodeling in the
      delayed restoration procedure was seen to occur from 4 to 12 months after implant
      placement. No significant differences were recorded between the two procedures in
      terms of DeltaFST and DeltaWKG. A loss of the papillary soft tissues before
      restoration, followed by a reestablishment after restoration, seemed to be
      verified for the delayed group, for which the papilla index went from the minimum
      of 0 at 4 months to a value of 2 at 24 months. Moreover, the immediate
      restoration procedure seemed to be more promising in terms of healing times and
      costs. CONCLUSION: Immediate restoration of implants installed in fresh
      extraction sockets was at least as effective and safe as delayed restoration.

PMID- 24852762
TI  - A body, a dog, and a fistful of scats.
AB  - Dogs and coyotes are the most frequently reported canids responsible for
      scavenging human remains. We present the case of a 90-year-old woman whose
      mummified body was found in her home showing partial destruction of the thorax
      and extremities and absence of the cranium. The victim lived with a beagle dog
      whose dead body was also found, along with abundant scats throughout the house.
      Scavenging by the decedent's pet was the proposed hypothesis for the partial
      dismemberment and consumption of her body. Forensic analysis revealed that the
      victim died as a result of an accidental fracture of the proximal femoral
      epiphysis. Bone exam showed signs of canine scavenging on certain bones.
      Macroscopic and histological analyses of the dog feces revealed the presence of
      small bone fragments within scats. All the collected data supported the
      hypothesis that the decedent's pet fed on the victim following her death. The
      current case illustrates that forensic anthropology has much more to offer than
      personal identification and determining the manner of death. Systematic search
      and examination of scat deposits recovered from the scene may be very useful in
      the medicolegal investigation, identifying the origin of body mutilation and
      particularly the animal responsible for any scavenging. 

PMID- 24852764
TI  - A highly efficient mesoscopic solar cell based on CH3NH3PbI(3-x)Cl(x) fabricated
      via sequential solution deposition.
AB  - A mixed halide perovskite of CH3NH3PbI(3-x)Cl(x) is synthesized via two-step
      sequential solution deposition by using a mixture of PbCl2 and PbI2 as the
      precursor to overcome the low solubility of pure PbCl2 with easy morphology
      control. 11.7% power conversion efficiency is achieved for the mesoscopic cell,
      much higher than the cell constructed via a spin-coating process.

PMID- 24852763
TI  - Child externalizing behavior problems linked to genetic and non-genetic variation
      in dental caries.
AB  - The association of environmental and genetic variation in caries with child
      externalizing behavior problems (inattention, hyperactivity, impulsivity, and
      defiance) was studied in a sample of 239 pairs of 3- to 8-year-old impoverished
      Brazilian twins. It was hypothesized that externalizing problems would show a
      stronger positive association with environmental than genetic variation in
      caries. Univariate twin models were estimated to parse variation in caries into
      three components: additive genetic (A), shared environment (C) and non-shared
      environment/error (E). Age-adjusted associations between externalizing problems
      and each variance component were tested. Contrary to the hypothesis, modest but
      very consistent negative associations were found between externalizing problems
      and both genetic and environmental variation in caries. Mutans streptococci and
      sweetness preference did not explain the negative associations of caries and
      externalizing problems. Externalizing problems in non-medicated children were
      associated with less dental decay that could be explained by both genetic and
      environmental factors.

PMID- 24852765
TI  - [Neuro-orthopedics].

PMID- 24852766
TI  - [Conservative and operative treatment of working age patients with gonarthritis.
      Economic considerations].
AB  - BACKGROUND: The development of the overall achievements for hospital performance
      since the introduction in Germany of the diagnosis-related groups (DRG) system in
      2003 is the subject of healthcare political discussion. The field of prosthetics
      is often at the center of considerations. PROBLEM: After consideration of the
      development of achievements with international and regional earnings, the
      question was investigated how the average expenditure for patients with
      gonarthritis developed in a time period of 1 year before and after implantation
      of total knee prostheses. MATERIAL AND METHODS: The study was based on individual
      patient data from the accounting data of the AOK (General Regional Healthcare
      Insurance) from the categories, inpatient care, panel physician treatment,
      pharmaceuticals and medicines as well as disability leave periods. The data
      include the average expenditure and disability times calculated by the AOK for
      individual patients 12 months before and 12 months after implantation of a total
      knee prosthesis. The methods were selected because the international
      classification of diseases (ICD) coding does not allow a differentiation in the
      degree of severity and, therefore, a comparison of patients who were only
      conservatively treated within the scope of panel physicians which would have led
      to problems in risk adjustment. Due to a lack of coding guidelines for treatment
      by panel physicians, the accuracy of the diagnosis is also limited in comparison
      to inpatient treatment data. RESULTS: The expenditure and the average disability
      leave for gonarthritis patients were higher in the year following implantation of
      total knee prostheses than in the year prior to implantation. DISCUSSION: No
      conclusions can be drawn from the provision of service data with respect to the
      quality of life of the patients. Investigations over a longer time period seem to
      be necessary.

PMID- 24852767
TI  - MiR-16 induced the suppression of cell apoptosis while promote proliferation in
      esophageal squamous cell carcinoma.
AB  - BACKGROUND/AIMS: MicroRNAs (miRNAs) are non-coding small RNAs that regulate cell
      proliferation and functions by interfering with the translation of target mRNAs.
      Altered expression of miRNA is known to induce various human malignancies, but
      little is known about the role of miRNAs in esophageal squamous cell carcinoma
      (ESCC). METHODS: RT-PCR and Western blot were used to examine the expression of
      miRNAs and candidate genes in 40 pairs of squamous cell carcinoma of human. MiR
      16 mimics and inhibitor were transfected in human TE-1 and Eca-109 cells before
      detecting the cell migration, proliferation, apoptosis and cell cycle. The
      regulation mechanism was confirmed by luciferase reporter assay. Caspase-3 and 9
      were detected by RT-PCR and Western blot. RESULTS: Aberrant increased level of
      miR-16 was detected in the ESCC tissues compared with the corresponding adjacent
      tumor tissues. MiR-16 could inhibit cell apoptosis while promote cell
      proliferation by down-regulating RECK and SOX6 in TE-1 and Eca-109 cell lines
      through binding the 3'UTR of both RECK and SOX6 mRNA. CONCLUSIONS: Aberrant
      expression level of miR-16 could suppress cell apoptosis while promote growth by
      regulating RECK and SOX6 which play important roles in the pathogenesis of ESCC.

PMID- 24852768
TI  - A review of phosphodiesterase-inhibition and the potential role for
      phosphodiesterase 4-inhibitors in clinical dermatology.
AB  - BACKGROUND: Phosphodiesterase inhibitors are commonly used drugs. Specific
      phosphodiesterase inhibitors with anti-inflammatory properties are being assessed
      as dermatological treatments. PURPOSE: To describe important aspects of
      phosphodiesterase inhibition and the safety and efficacy of 2 phosphodiesterase-
      4 inhibitors being studied for the treatment of dermatologic diseases METHODS: We
      did a non-systematic analysis of literature on phosphodiesterase inhibition
      followed by a review of published information on apremilast and topical AN2728
      and their use for psoriasis and atopic dermatitis. FINDINGS: Apremilast and
      topical AN2728 have modest efficacy in treatment of psoriasis. Apremilast
      achieved PASI-75 scores ranging from 24-33%. In phase 2 studies, AN2728 had
      modest efficacy for psoriasis (40% of patients achieved a >= 2 grade improvement
      as assessed by the Overall target Plaque Severity Score). In phase 2 studies of
      AN2728 use in atopic dermatitis, subjects achieved a 71% improvement from
      baseline Atopic Dermatitis Severity Index. In all studies, most adverse effects
      were minimal. The limitations of this paper are the limited number of published
      studies, the lack of long-term data, and the lack of head -to - head trials
      directly comparing phosphodiesterase inhibitors with other treatments.
      CONCLUSION: Phosphodiesterase inhibitors constitute a widely used class of drugs
      that may see growing use for inflammatory dermatologic diseases.

PMID- 24852769
TI  - Common reasons why acne patients call the office.
AB  - BACKGROUND: Communication between physicians and patients is essential to
      providing proper medical care. At times, patients leave visits with
      insufficiently addressed questions. These questions prompt patients to call the
      clinic for additional information, which disrupts the flow of care, delays proper
      treatment, and reduces patient satisfaction. PURPOSE: We aim to examine acne
      patients' post-visit questions to develop interventions to improve patient
      education and reduce call backs. METHODS: A retrospective electronic medical
      record chart review was performed involving Wake Forest Baptist Health
      Dermatology clinic visits between October 1, 2012 and October 31, 2012. We
      identified acne patients using clinic visit notes and recorded their telephone
      calls to the clinic between October 1, 2012 and March 29, 2013. RESULTS: Of 315
      acne patients, 31 (9.8%) called the clinic. Isotretinoin was the subject of 66.7%
      of the calls, half of which involved questions about potential side effects.
      Other calls addressed topical medications, acne symptoms, and pharmacy requests.
      LIMITATIONS: The study involved one center and email and fax correspondence was
      not captured. CONCLUSIONS: We found gaps in communication sufficient to require
      patients to call in for support, specifically regarding oral isotretinoin
      treatment. Interventions to address these questions have the potential to improve
      quality of care.

PMID- 24852770
TI  - Multinucleate cell angiohistiocytoma: a case report and review of the literature.
AB  - Multinucleate cell angiohistiocytoma (MCAH) is a rare, benign vascular
      proliferation. Fewer than 80 cases have been reported to date, which may relate
      to under-recognition of this entity. Lesions are commonly asymptomatic and appear
      as erythematous to violaceous papules on the lower extremities and dorsal hands
      of middle-aged to elderly women. The characteristic histopathologic and
      immunohistochemical features of MCAH are essential for definitive diagnosis of
      MCAH. Multinucleate cell angiohistiocytoma follows a slowly progressive course,
      although spontaneous regression has been reported in rare cases. We present a
      case of MCAH to increase awareness and elucidate the characteristic clinical and
      histopathologic features of this disorder. 

PMID- 24852771
TI  - [Acquired cutis laxa associated with monoclonal gammopathy and lambda light chain
      deposition disease].
AB  - Cutis laxa is a rare entity characterized clinically by redundant skin that gives
      an appearance of premature aging. The appearance relates to a loss of elasticity
      because of the destruction of elastic fibers that affects the skin and other
      organs. It may be associated with inflammatory conditions or diseases, such as
      plasma cell dyscrasias. We report the case of a 54-year-old man with acquired
      cutis laxa, which preceded the development of IgG-lambda monoclonal gammopathy
      with lambda light chain deposits in the kidney. The patient had a fatal outcome
      owing to severe and rapidly progressive renal failure. We emphasize the
      importance of recognizing a plasma cell dyscrasia in a patient with cutis laxa,
      although this association is rare. 

PMID- 24852772
TI  - Multiple clustered and focally atrophic dermatofibromas (DF).
AB  - Multiple clustered dermatofibromas describes a confluence of dermatofibromas in
      one anatomic location. We describe a 32-year-old man who presented for evaluation
      owing to skin papules and plaques and concerns about malignancy. Repeat
      histopathological evaluation found no evidence for dermatofibrosarcoma
      protuberans. Our case presents this relatively rare condition and discusses
      observation along with potential treatment options. 

PMID- 24852774
TI  - Regression of cutaneous invasive squamous cell carcinoma in a patient with
      chronic cutaneous graft versus host disease.
AB  - Numerous complications can be observed in the post-transplant period among
      recipients of hematopoietic stem cells including graft-versus-host disease
      (GVHD), which is associated with significant morbidity and mortality. On the
      other hand, graft versus tumor (GVT) effect is a well-described phenomenon in
      patients with hematologic malignancies and has also been reported in renal cell
      cancer, ovarian cancer, breast carcinoma, and melanoma. We describe spontaneous
      regression of a cutaneous invasive squamous cell carcinoma and multifocal
      atypical intraepidermal proliferations in a patient with chronic graft-versus
      host disease following initiation of extracorporeal photopheresis (ECP). This
      observation raises questions regarding the GVT in cutaneous neoplasms and
      potential immunomodulatory effects of ECP. 

PMID- 24852773
TI  - Cetirizine-induced acute generalized exanthematous pustulosis: a serious reaction
      to a commonly used drug.
AB  - Acute generalized exanthematous pustulosis (AGEP) is an abrupt cutaneous adverse
      reaction usually in response to medications. It is generally a self-limiting
      disease if diagnosed promptly and the offending agent discontinued. Cetirizine, a
      commonly used anti-histamine medication for the treatment of allergic diseases
      has few reported side effects and is normally well-tolerated and effective.
      Herein, the first reported case of cetirizine induced AGEP is presented, followed
      by a discussion of the clinical and pathological aspects of this adverse
      cutaneous reaction to a widely used drug. Awareness of this reaction is vital
      owing to the extensive use of cetirizine and the importance of drug cessation
      once the reaction is identified. Lastly, other pustular cutaneous reactions may
      present similarly and therefore accurate identification of this disease can
      prevent unnecessary diagnostic testing. 

PMID- 24852775
TI  - [Cervical adenocarcinoma with lymphatic spread presenting as carcinoma "en
      cuirasse"of the vulva: case report].
AB  - We report the case of a patient with carcinoma "en cuirasse" of the vulva. CASE
      REPORT: A female patient presented complaining of inguinal lymphadenopathy. Lymph
      node excision, immunohistochemistry analyses, and further exams showed the
      presence of cervical adenocarcinoma. The cancer was surgically removed and the
      patient was treated with radiotherapy and chemotherapy with a good initial
      response. Some months later she presented with intense edema of the lower limbs,
      hardening and thickening of the labia majora, and pelvic and genital ulceration.
      A cutaneous biopsy with subsequent immunohistochemical staining showed lymphatic
      dissemination of adenocarcinoma to the vulva. DISCUSSION: Carcinoma "en cuirasse"
      is a rare presentation of cutaneous metastasis in which the affected skin shows
      hardening and induration, acquiring a sclerodermoid appearance. This is, to the
      best of our knowledge, the first report in Brazil of carcinoma "en cuirasse" of
      the vulva associated with cervical adenocarcinoma.

PMID- 24852776
TI  - Disseminated cutaneous mycobacterium avium complex in a person with AIDS.
AB  - A cutaneous Mycobacterium avium complex (MAC) infection is a rare infection that
      can occur through direct inoculation or via dissemination to the skin. We report
      an interesting case of disseminated cutaneous MAC infection in a 45-year-old man
      with acquired immunodeficiency syndrome (AIDS), currently treated with highly
      active antiretroviral therapy (HAART) and MAC prophylaxis. 

PMID- 24852777
TI  - Improvement in severe psoriasis associated with isoniazid treatment.
AB  - A 67 year-old man was diagnosed 10 years ago with severe plaque psoriasis and was
      hospitalized for re-evaluation of therapy. He was treated previously with topical
      corticosteroids, methotrexate, and phototherapy. As part of the assessment
      protocol for initiation of biological treatment, a tuberculin skin test was done,
      which was positive without signs of active tuberculosis. Isoniazid therapy was
      started with marked improvement of psoriatic lesions before biologic treatment
      could be initiated. 

PMID- 24852778
TI  - [Superimposed lichen planus pigmentosus].
AB  - Lichen planus pigmentosus is an uncommon variant of lichen planus that is
      characterized by the insidious onset of dark brown macules in sun-exposed areas
      and flexural folds. Superimposed linear lichen planus is an exceedingly rare
      disorder, but it has been found in both lichen planopilaris and lichen planus
      types. A 39-year-old woman is presented showing a segmental and linear lichen
      planus associated with non-segmental lesions meeting all criteria for the
      diagnosis of superimposed linear planus pigmentosus. The segmental lesions were
      always more pronounced. 

PMID- 24852779
TI  - Cervicofacial actinomycosis: a long forgotten infectious complication of
      immunosuppression - report of a case and review of the literature.
AB  - Actinomycosis is a rare chronic granulomatous infection caused by Gram-positive,
      non-acid-fast, anaerobic to microaerophilic bacteria.We report a case of
      cervicofacial actinomycosis in an 86-year-old woman undergoing immunosuppressive
      therapy with azathioprine and prednisone for rheumatoid arthritis. She underwent
      a dental treatment several months earlier. The diagnosis of culture-negative
      actinomycosis was based on histolopathology findings and the isolation of
      companion bacteria. The patient was treated with amoxicillin-clavulanic acid for
      3 months, which produced complete clearance of her cervicofacial
      actinomycosis.Our case points out the pitfalls of diagnostic procedures in
      actinomycosis and the ability of this rare disease to mimic other medical
      conditions. 

PMID- 24852781
TI  - Dermatology on Tumblr.
AB  - Tumblr broke into the social media scene in 2007 as a micro-blogging platform
      that hosts 169 million blogs, 75 billion total posts, and 111 million posts daily
      to date. This study aimed to determine the presence of dermatology-focused
      journals, organizations, and groups on Tumblr. These were entered into the Tumblr
      search query to identify affiliated Tumblr blogs and 'dermatology Tumblr' was
      searched on Google to determine the first four distinct results that were active
      within the last six months. None of the dermatology-focused journals,
      organizations, or groups maintained a Tumblr blog and three of the first four
      blogs on Google were maintained by private practices. In conclusion, Tumblr
      remains a social media domain that lacks a strong presence from dermatology
      journals and organizations, remaining an untapped resource for information
      dissemination and interaction with the public. 

PMID- 24852780
TI  - Omphalolith: a rare entity but important to recognize.
AB  - Omphalolith (umbolith) is an uncommon entity under normal circumstances. However,
      in a deeply retracted umbilicus in an obese individual, the accumulation of sebum
      and keratin may lead to the formation of a stone. This calculus may remain
      undiagnosed for many years until revealed by secondary infection or ulceration.
      We report an interesting case of an omphalolith in a young woman. In our
      literature search, very few cases of omphalolith have been reported. 

PMID- 24852782
TI  - Nodular goiter with thyroid antibodies in chronic idiopathic urticaria.
AB  - We report a case of chronic idiopathic urticaria associated with nodular goiter
      and Graves disease. The urticaria resolved with normalization of the thyroid
      function. 

PMID- 24852783
TI  - Bilateral suborbital rash: a dermatologic manifestation of neuropsychiatric
      disease in a pediatric patient.
AB  - A 10-year-old girl presented with a new onset bilateral suborbital rash.
      Dermatologic examination revealed violaceous, non-tender, well-demarcated patches
      with an atypical distribution and pigmentation. After further investigation, a
      diagnosis of Munchausen syndrome was made and the patient was referred to her
      primary care provider for further management. 

PMID- 24852784
TI  - Citation classics and top-cited authors of psoriasis in five high-impact general
      medical journals, 1970-2012.
AB  - Psoriasis is a relevant topic for publication in general medical journals. We
      conducted a search of the Thomson Reuters' Science Citation using the search term
      of "psoriasis" in five high-impact general medical journals. All citation
      classics from 1970 to 2012 were included and each author's total number of
      citations was summated. A total of 51 citation classics were collected. The most
      common topic of publication was psoriasis treatment (37), especially biologic
      agents (16). A total of 1037 authors of psoriasis articles were identified in our
      study and the top 25 most-cited authors were compiled. We hope our citation
      analysis provides a historical perspective and highlights the work of our
      colleagues and predecessors. 

PMID- 24852785
TI  - Dissecting cellulitis (Perifolliculitis Capitis Abscedens et Suffodiens): a
      comprehensive review focusing on new treatments and findings of the last decade
      with commentary comparing the therapies and causes of dissecting cellulitis to
      hidradenitis suppurativa.
AB  - Dissecting cellulitis (DC) also referred to as to as perifolliculitis capitis
      abscedens et suffodiens (Hoffman) manifests with perifollicular pustules,
      nodules, abscesses and sinuses that evolve into scarring alopecia. In the U.S.,
      it predominantly occurs in African American men between 20-40 years of age. DC
      also occurs in other races and women more rarely. DC has been reported worldwide.
      Older therapies reported effective include: low dose oral zinc, isotretinoin,
      minocycline, sulfa drugs, tetracycline, prednisone, intralesional triamcinolone,
      incision and drainage, dapsone, antiandrogens (in women), topical clindamycin,
      topical isotretinoin, X-ray epilation and ablation, ablative C02 lasers, hair
      removal lasers (800nm and 694nm), and surgical excision. Newer treatments
      reported include tumor necrosis factor blockers (TNFB), quinolones, macrolide
      antibiotics, rifampin, alitretinoin, metronidazole, and high dose zinc sulphate
      (135-220 mg TID). Isotretinoin seems to provide the best chance at remission, but
      the number of reports is small, dosing schedules variable, and the long term
      follow up beyond a year is negligible; treatment failures have been reported.
      TNFB can succeed when isotretinoin fails, either as monotherapy, or as a bridge
      to aggressive surgical treatment, but long term data is lacking. Non-medical
      therapies noted in the last decade include: the 1064 nm laser, ALA-PDT, and
      modern external beam radiation therapy. Studies that span more than 1 year are
      lacking. Newer pathologic hair findings include: pigmented casts, black dots, and
      "3D" yellow dots. Newer associations include: keratitis-ichthyosis-deafness
      syndrome, Crohn disease and pyoderma gangrenosum. Older associations include
      arthritis and keratitis. DC is likely a reaction pattern, as is shown by its
      varied therapeutic successes and failures. The etiology of DC remains enigmatic
      and DC is distinct from hidradenitis suppurativa, which is shown by their varied
      responses to therapies and their histologic differences. Like HS, DC likely
      involves both follicular dysfunction and an aberrant cutaneous immune response to
      commensal bacteria, such as coagulase negative staphylococci. The incidence of DC
      is likely under-reported. The literature suggests that now most cases of DC can
      be treated effectively. However, the lack of clinical studies regarding DC
      prevents full understanding of the disease and limits the ability to define a
      consensus treatment algorithm. 

PMID- 24852786
TI  - Evaluation of Finnish Diabetes Risk Score in screening undiagnosed diabetes and
      prediabetes among U.S. adults by gender and race: NHANES 1999-2010.
AB  - OBJECTIVE: To evaluate the performance of Finnish Diabetes Risk Score (FINDRISC)
      in detecting undiagnosed diabetes and prediabetes among U.S. adults by gender and
      race. METHODS: This cross-sectional analysis included participants (aged >=20
      years) from the National Health and Nutrition Examination Survey (NHANES) 1999
      2010. Sensitivity, specificity, area under the receiver operating characteristic
      (ROC) curve and the optimal cutoff points for identifying undiagnosed diabetes
      and prediabetes were calculated for FINDRISC by gender and race/ethnicity.
      RESULTS: Among the 20,633 adults (>=20 years), 49.8% were women and 53.0% were
      non-Hispanic White. The prevalence of undiagnosed diabetes and prediabetes was
      4.1% and 35.6%, respectively. FINDRISC was positively associated with the
      prevalence of diabetes (OR = 1.48 for 1 unit increase, p<0.001) and prediabetes
      (OR = 1.15 for 1 unit increase, p<0.001). The area under ROC for detecting
      undiagnosed diabetes was 0.75 for total population, 0.74 for men and 0.78 for
      women (p = 0.04); 0.76 for White, 0.76 for Black and 0.72 for Hispanics (p = 0.03
      for White vs. Hispanics). The area under ROC for detecting prediabetes was 0.67
      for total population, 0.66 for men and 0.70 for women (p<0.001); 0.68 for White,
      0.67 for Black and 0.65 for Hispanics (p<0.001 for White vs. Hispanics). The
      optimal cutoff point was 10 (sensitivity = 0.75) for men and 12 (sensitivity =
      0.72) for women for detecting undiagnosed diabetes; 9 (sensitivity = 0.61) for
      men and 10 (sensitivity = 0.69) for women for detecting prediabetes. CONCLUSIONS:
      FINDRISC is a simple and non-invasive screening tool to identify individuals at
      high risk for diabetes in the U.S. adults.

PMID- 24852788
TI  - A phase II study of cyclophosphamide, etoposide, vincristine and prednisone
      (CEOP) alternating with pralatrexate (P) as front line therapy for patients with
      peripheral T-cell lymphoma (PTCL): preliminary results from the T-Cell Consortium
      trial.

PMID- 24852789
TI  - Analysis of peripheral T-cell lymphoma (PTCL) subtype by race and geography using
      the Comprehensive Oncology Measures for Peripheral T-Cell Lymphoma Treatment
      (COMPLETE) dataset.

PMID- 24852787
TI  - Community knowledge and attitudes and health workers' practices regarding non
      malaria febrile illnesses in eastern Tanzania.
AB  - INTRODUCTION: Although malaria has been the leading cause of fever for many
      years, with improved control regimes malaria transmission, morbidity and
      mortality have decreased. Recent studies have increasingly demonstrated the
      importance of non-malaria fevers, which have significantly improved our
      understanding of etiologies of febrile illnesses. A number of non-malaria febrile
      illnesses including Rift Valley Fever, dengue fever, Chikungunya virus infection,
      leptospirosis, tick-borne relapsing fever and Q-fever have been reported in
      Tanzania. This study aimed at assessing the awareness of communities and
      practices of health workers on non-malaria febrile illnesses. METHODS: Twelve
      focus group discussions with members of communities and 14 in-depth interviews
      with health workers were conducted in Kilosa district, Tanzania. Transcripts were
      coded into different groups using MaxQDA software and analyzed through thematic
      content analysis. RESULTS: The study revealed that the awareness of the study
      participants on non-malaria febrile illnesses was low and many community members
      believed that most instances of fever are due to malaria. In addition, the
      majority had inappropriate beliefs about the possible causes of fever. In most
      cases, non-malaria febrile illnesses were considered following a negative Malaria
      Rapid Diagnostic Test (mRDT) result or persistent fevers after completion of anti
      malaria dosage. Therefore, in the absence of mRDTs, there is over diagnosis of
      malaria and under diagnosis of non-malaria illnesses. Shortages of diagnostic
      facilities for febrile illnesses including mRDTs were repeatedly reported as a
      major barrier to proper diagnosis and treatment of febrile patients. CONCLUSION:
      Our results emphasize the need for creating community awareness on other causes
      of fever apart from malaria. Based on our study, appropriate treatment of febrile
      patients will require inputs geared towards strengthening of diagnostic
      facilities, drugs availability and optimal staffing of health facilities.

PMID- 24852790
TI  - The combination of hypomethylating agents and histone deacetylase inhibitors
      (HDACi) are synergistically cytotoxic and reverse the malignant phenotype in
      preclinical models of T-cell lymphoma.

PMID- 24852791
TI  - Phase II trial of brentuximab vedotin for CD30+ cutaneous T-cell lymphomas and
      lymphoproliferative disorders.

PMID- 24852792
TI  - Preliminary results of a phase II study of single agent Bay 80-6946, a Novel PI3K
      inhibitor, in patients with relapsed/refractory, indolent or aggressive lymphoma.

PMID- 24852793
TI  - Romidepsin is effective and well-tolerated in patients >=60 years old with
      relapsed or refractory peripheral T-cell lymphoma (PTCL): analysis from phase 2
      trials.

PMID- 24852794
TI  - Commentary.

PMID- 24852795
TI  - Post-stroke depression therapy: where are we now?
AB  - Post-stroke depression is an important psychological consequence of ischemic
      stroke, and affects around one third of stroke patients at any time post-stroke.
      It has a negative impact on patient morbidity and mortality, and as such
      development of effective post-stroke recognition and treatment strategies are
      very important. There are several therapeutic strategies for post-stroke
      depression, including both pharmacological and non-pharmacological approaches. In
      this review, we present evidence regarding the underlying biology of post-stroke
      depression, commonalities between post-stroke depression and Major Depressive
      Disorder and explore several treatment approaches, including antidepressant
      therapy, psychotherapy, surgical therapy, electroconvulsive therapy, acupuncture,
      music therapy and natural products. Further experimental and clinical studies are
      required, particularly in emerging fields such as the role of nutraceuticals in
      the treatment of stroke. 

PMID- 24852796
TI  - A comparative analysis of the bistability switch for platelet aggregation by
      logic ODE based dynamical modeling.
AB  - A kinetic description of the fragile equilibrium in thrombozytes regulating blood
      flow would be an important basis for rational medical interventions. Challenges
      for such a model include regulation by a complex bistability switch that
      determines the transition from reversible to irreversible aggregation and sparse
      data on the kinetics. A so far scarcely applied technique is given by the
      derivation of ordinary differential equations from Boolean expressions, which are
      called logic ODEs. We employ a combination of light-scattering based thrombocyte
      aggregation data, western blot and calcium measurements to compare three
      different ODE approaches regarding their suitability to achieve a data-consistent
      model of the switch. Our analysis reveals the standardized qualitative dynamical
      system approach (SQUAD) to be a better choice than classical mass action
      formalisms. Furthermore, we analyze the dynamical properties of the platelet
      aggregation threshold as a basis for medical interventions such as novel platelet
      aggregation inhibitors. 

PMID- 24852797
TI  - Improved catalyzed reporter deposition, iCARD.
AB  - Novel reporters have been synthesized with extended hydrophilic linkers that in
      combination with polymerizing cross-linkers result in very efficient reporter
      deposition. By utilizing antibodies to stain HER2 proteins in a cell line model
      it is demonstrated that the method is highly specific and sensitive with
      virtually no background. The detection of HER2 proteins in tissue was used to
      visualize individual antigens as small dots visible in a microscope. Image
      analysis-assisted counting of fluorescent or colored dots allowed assessment of
      relative protein levels in tissue. Taken together, we have developed novel
      reporters that improve the CARD method allowing highly sensitive in situ
      detection of proteins in tissue. Our findings suggest that in situ protein
      quantification in biological samples can be performed by object recognition and
      enumeration of dots, rather than intensity-based fluorescent or colorimetric
      assays. 

PMID- 24852798
TI  - Hypothalamic attack: a wonderful artifact or a useful perspective on escalation
      and pathology in aggression? A viewpoint.
AB  - W.R. Hess' early demonstration of aggressive responses evoked by electrical
      stimulation in the cat's hypothalamus had a significant impact on the development
      of psychological and behavioral concepts. Many ideas on behavioral routines,
      allegedly organized in the brainstem, derive from his observation. Similar
      responses have since been evoked from the hypothalamus of many different species,
      suggesting that the mechanism mediating these responses is evolutionarily well
      preserved. However, these effects have also been portrayed as artificial
      responses to an artificial stimulus in an artificial environment. True enough;
      after many years of research, crucial questions on the underlying mechanism
      remain unanswered. Questions such as: How do they emerge in the first place? What
      neuronal elements mediate these responses? What is their role in "spontaneous"
      aggression? In the first part of this chapter we show methodology to study such
      questions in a consistent way using behavioral, physiological, anatomical, and
      pharmacological findings on hypothalamic attack in rats. In the second part we
      suggest that one important function of the underlying mechanism is to match the
      dynamics of the endocrine stress response with the dynamics of the behavioral and
      physiological requirements of coping with conflicts. This neuroendocrine
      behavioral matching seems crucial right from the first emergence of the
      aggressive response in inexperienced animals, up to the full-blown violent
      responding in fully experienced animals. Impeding these essential functions
      results in inadequate coping with conflicts. The stress response during a first
      conflict in an inexperienced individual in an unfamiliar environment seems to
      rapidly initialize a crucial change in a mechanism involved in the appraisal of
      social signals during conflict. That change has enduring consequences for future
      conflict strategies. This concept opens another perspective on "escalated" or
      "pathological" aggression, especially so in individuals with a dysfunctional
      stress response. 

PMID- 24852799
TI  - Stress, arousal, and sleep.
AB  - Stress is considered to be an important cause of disrupted sleep and insomnia.
      However, controlled and experimental studies in rodents indicate that effects of
      stress on sleep-wake regulation are complex and may strongly depend on the nature
      of the stressor. While most stressors are associated with at least a brief period
      of arousal and wakefulness, the subsequent amount and architecture of recovery
      sleep can vary dramatically across conditions even though classical markers of
      acute stress such as corticosterone are virtually the same. Sleep after stress
      appears to be highly influenced by situational variables including whether the
      stressor was controllable and/or predictable, whether the individual had the
      possibility to learn and adapt, and by the relative resilience and vulnerability
      of the individual experiencing stress. There are multiple brain regions and
      neurochemical systems linking stress and sleep, and the specific balance and
      interactions between these systems may ultimately determine the alterations in
      sleep-wake architecture. Factors that appear to play an important role in stress
      induced wakefulness and sleep changes include various monominergic
      neurotransmitters, hypocretins, corticotropin releasing factor, and prolactin. In
      addition to the brain regions directly involved in stress responses such as the
      hypothalamus, the locus coeruleus, and the amygdala, differential effects of
      stressor controllability on behavior and sleep may be mediated by the medial
      prefrontal cortex. These various brain regions interact and influence each other
      and in turn affect the activity of sleep-wake controlling centers in the brain.
      Also, these regions likely play significant roles in memory processes and
      participate in the way stressful memories may affect arousal and sleep. Finally,
      stress-induced changes in sleep-architecture may affect sleep-related neuronal
      plasticity processes and thereby contribute to cognitive dysfunction and
      psychiatric disorders. 

PMID- 24852800
TI  - Potential of organ donation from deceased donors: study from a public sector
      hospital in India.
AB  - Deceased donor organ programme is still in infancy in India. Assessing deceased
      donation potential and identifying barriers to its utilization are required to
      meet needs of patients with organ failure. Over a 6-month period, we identified
      and followed all presumed brainstem dead patients secondary to brain damage. All
      patients requiring mechanical ventilation with no signs of respiratory activity
      and dilated, fixed and nonreacting pupils were presumed to be brainstem dead. All
      events from suspicion of brainstem death (BSD) to declaration of BSD, approach
      for organ donation, recovery and transplants were recorded. Subjects were
      classified as possible, potential and effective donors, and barriers to donation
      were identified at each step. We identified 80 presumed brainstem dead patients
      over the study period. The mean age of this population was 35.9 years, and 67.5%
      were males. When formally asked for consent for organ donation (n = 49), 41
      patients' relatives refused. The conversion rate was only 8.2%. The number of
      possible, potential and effective donors per million population per year were
      127, 115.7 and 9.5, respectively. The poor conversion rate of 8.2% suggests a
      huge potential for improvement. Family refusal in majority of cases reflects poor
      knowledge and thus warrants interventions at community level. 

PMID- 24852801
TI  - Predicting 3-year mortality after percutaneous coronary intervention: updated
      logistic clinical SYNTAX score based on patient-level data from 7 contemporary
      stent trials.
AB  - OBJECTIVES: This study aimed to update the Logistic Clinical SYNTAX score to
      predict 3-year survival after percutaneous coronary intervention (PCI) and
      compare the performance with the SYNTAX score alone. BACKGROUND: The SYNTAX score
      is a well-established angiographic tool to predict long-term outcomes after PCI.
      The Logistic Clinical SYNTAX score, developed by combining clinical variables
      with the anatomic SYNTAX score, has been shown to perform better than the SYNTAX
      score alone in predicting 1-year outcomes after PCI. However, the ability of this
      score to predict long-term survival is unknown. METHODS: Patient-level data (N =
      6,304, 399 deaths within 3 years) from 7 contemporary PCI trials were analyzed.
      We revised the overall risk and the predictor effects in the core model (SYNTAX
      score, age, creatinine clearance, and left ventricular ejection fraction) using
      Cox regression analysis to predict mortality at 3 years. We also updated the
      extended model by combining the core model with additional independent predictors
      of 3-year mortality (i.e., diabetes mellitus, peripheral vascular disease, and
      body mass index). RESULTS: The revised Logistic Clinical SYNTAX models showed
      better discriminative ability than the anatomic SYNTAX score for the prediction
      of 3-year mortality after PCI (c-index: SYNTAX score, 0.61; core model, 0.71; and
      extended model, 0.73 in a cross-validation procedure). The extended model in
      particular performed better in differentiating low- and intermediate-risk groups.
      CONCLUSIONS: Risk scores combining clinical characteristics with the anatomic
      SYNTAX score substantially better predict 3-year mortality than the SYNTAX score
      alone and should be used for long-term risk stratification of patients undergoing
      PCI.

PMID- 24852803
TI  - Second-generation drug-eluting stents and bioresorbable vascular scaffolds in
      patients with diabetes.

PMID- 24852802
TI  - Everolimus-eluting Xience v/Promus versus zotarolimus-eluting resolute stents in
      patients with diabetes mellitus.
AB  - OBJECTIVES: This study sought to compare everolimus-eluting stents (EES) versus
      Resolute zotarolimus-eluting stents (ZES) in terms of patient- or stent-related
      clinical outcomes in an "all-comer" group of patients with diabetes mellitus (DM)
      who underwent percutaneous coronary intervention. BACKGROUND: DM significantly
      increases the risk of adverse events after percutaneous coronary intervention.
      The efficacy and safety of second-generation drug-eluting stents, in particular
      EES versus ZES, in patients with DM have not been extensively evaluated. METHODS:
      Patients with DM (1,855 of 5,054 patients, 36.7%) from 2 prospective registries
      (the EXCELLENT [Efficacy of Xience/Promus Versus Cypher in Reducing Late Loss
      After Stenting] registry and RESOLUTE-Korea [Registry to Evaluate the Efficacy of
      Zotarolimus-Eluting Stent]) who were treated with EES (n = 1,149) or ZES (n =
      706) were compared. Stent-related outcome was target lesion failure (TLF), and
      patient-oriented composite events were a composite of all-cause mortality, any
      myocardial infarction, and any revascularization. RESULTS: Despite a higher risk
      patient profile in the ZES group, both TLF (43 of 1,149 [3.7%] vs. 25 of 706
      [3.5%], p = 0.899) and patient-oriented composite events (104 of 1,149 [9.1%] vs.
      72 of 706 [10.2%], p = 0.416) were similar between the EES and ZES in patients
      with DM at 1 year. In those without DM, EES and ZES also showed comparable
      incidence of TLF (39 of 1,882 [2.1%] vs. 33 of 1,292 [2.6%], p = 0.370) and
      patient-oriented composite events (119 of 1,882 [6.3%] vs. 81 of 1,292 [6.3%], p
      = 0.951), which were all significantly lower than in the DM patients. These
      results were corroborated by similar findings from the propensity score-matched
      cohort. Upon multivariate analysis, chronic renal failure was the most powerful
      predictor of TLF in DM patients (hazard ratio: 4.39, 95% confidence interval:
      1.91 to 10.09, p < 0.001). CONCLUSIONS: After unrestricted use of second
      generation drug-eluting stents in all-comers receiving percutaneous coronary
      intervention, both EES and ZES showed comparable clinical outcomes in the
      patients with DM up to 1 year of follow-up. DM compared with non-DM patients
      showed significantly worse patient- and stent-related outcomes. Nonetheless,
      overall incidences of TLF were low, even in the patients with DM, suggesting
      excellent safety and efficacy of both types of second-generation drug-eluting
      stents in this high-risk subgroup of patients.

PMID- 24852805
TI  - After 3 decades, at long last, a new device to deal with calcific lesions.

PMID- 24852804
TI  - Pivotal trial to evaluate the safety and efficacy of the orbital atherectomy
      system in treating de novo, severely calcified coronary lesions (ORBIT II).
AB  - OBJECTIVES: The ORBIT II (Evaluate the Safety and Efficacy of OAS in Treating
      Severely Calcified Coronary Lesions) trial evaluated the safety and efficacy of
      the coronary Orbital Atherectomy System (OAS) to prepare de novo, severely
      calcified coronary lesions for stent placement. BACKGROUND: Despite advances in
      interventional techniques, treatment of calcified coronary lesions remains a
      challenge. Stent placement in these lesions may result in stent underexpansion,
      malapposition, and procedural complications. METHODS: ORBIT II is a prospective,
      multicenter, nonblinded clinical trial that enrolled 443 consecutive patients
      with severely calcified coronary lesions at 49 U.S. sites from May 25, 2010, to
      November 26, 2012. Investigators used the centrifugal action of the OAS diamond
      coated crown to modify calcified lesions prior to stent placement. RESULTS: The
      pre-procedure mean minimal lumen diameter of 0.5 mm increased to 2.9 mm after the
      procedure. The primary safety endpoint was 89.6% freedom from 30-day major
      adverse cardiac events compared with the performance goal of 83%. The primary
      efficacy endpoint (residual stenosis <50% post-stent without in-hospital major
      adverse cardiac events) was 88.9% compared with the performance goal of 82%.
      Stent delivery occurred successfully in 97.7% of cases with <50% stenosis in
      98.6% of subjects. Low rates of in-hospital Q-wave myocardial infarction (0.7%),
      cardiac death (0.2%), and target vessel revascularization (0.7%) were reported.
      CONCLUSIONS: The ORBIT II coronary OAS trial met both the primary safety and
      efficacy endpoints by significant margins. Preparation of severely calcified
      plaque with the OAS not only helped facilitate stent delivery, but improved both
      acute and 30-day clinical outcomes compared with the outcomes of historic control
      subjects in this difficult-to-treat patient population. (Evaluate the Safety and
      Efficacy of OAS in Treating Severely Calcified Coronary Lesions [ORBIT II];
      NCT01092416).

PMID- 24852807
TI  - Serial 2-dimensional and 3-dimensional optical coherence tomography assessment of
      overhanging struts of drug-eluting absorbable metal scaffold: "DREAMS" for jailed
      side branch?

PMID- 24852808
TI  - Neoatherosclerosis: fooling mother nature.

PMID- 24852806
TI  - Effects of transcatheter pulmonary valve replacement on the hemodynamic and
      ventricular response to exercise in patients with obstructed right ventricle-to
      pulmonary artery conduits.
AB  - OBJECTIVES: This study sought to investigate the effects of exercise on the right
      ventricle in patients with an obstructed right ventricular outflow tract (RVOT)
      conduit before and after transcatheter pulmonary valve replacement (TPVR).
      BACKGROUND: Conventionally, assessment of the right ventricle in congenital heart
      disease patients with dysfunctional RVOT conduits is performed at rest. However,
      this does not reflect dynamic exercise changes. METHODS: Exercise stress
      echocardiography (ESE) before and 6 months after TPVR was performed. ESE protocol
      included measurement of rest and immediate post-exercise RVOT maximal
      instantaneous gradients (MIGs), right ventricular (RV) systolic pressure, 2
      dimensional fractional area change, and global longitudinal strain (GLS).
      RESULTS: Twenty patients with RVOT conduit obstruction (median age, 18 years),
      the majority (n = 14) with tetralogy of Fallot, completed the study. Pre-TPVR,
      the median resting MIG across the RVOT was 53 mm Hg (23 to 95 mm Hg) and
      increased to 93 mm Hg (49 to 156 mm Hg; p < 0.001) with exercise. After TPVR, the
      median MIG at rest was 26 mm Hg (6 to 41 mm Hg, and after exercise, it was 45 mm
      Hg (9 to 102 mm Hg), both significantly lower than before TPVR (p <= 0.001), but
      there was still a substantial increase in gradient with exercise in many
      patients. The RV fractional area change, RV GLS, and left ventricular GLS, both
      at rest and after exercise, were significantly greater after TPVR than before. A
      greater pre-TPVR exercise-related increase in RV function was associated with
      improvement in peak Vo2 after TPVR (p = 0.01). CONCLUSIONS: In patients with
      obstructed RVOT conduits, TPVR resulted in significant improvement in conduit
      stenosis and RV function at both rest and at peak exercise and in exercise
      cardiopulmonary function. The ability to augment RV function at peak exercise
      before TPVR was associated with improved exercise capacity 6 months after TPVR.

PMID- 24852809
TI  - Noncardiac pathology exposed at coronary angiography for ST-segment elevation.

PMID- 24852810
TI  - A wireless platform for in vivo measurement of resistance properties of the
      gastrointestinal tract.
AB  - Active locomotion of wireless capsule endoscopes has the potential to improve the
      diagnostic yield of this painless technique for the diagnosis of gastrointestinal
      tract disease. In order to design effective locomotion mechanisms, a quantitative
      measure of the propelling force required to effectively move a capsule inside the
      gastrointestinal tract is necessary. In this study, we introduce a novel wireless
      platform that is able to measure the force opposing capsule motion, without
      perturbing the physiologic conditions with physical connections to the outside of
      the gastrointestinal tract. The platform takes advantage of a wireless capsule
      that is magnetically coupled with an external permanent magnet. A secondary
      contribution of this manuscript is to present a real-time method to estimate the
      axial magnetic force acting on a wireless capsule manipulated by an external
      magnetic field. In addition to the intermagnetic force, the platform provides
      real-time measurements of the capsule position, velocity, and acceleration. The
      platform was assessed with benchtop trials within a workspace that extends 15 cm
      from each side of the external permanent magnet, showing average error in
      estimating the force and the position of less than 0.1 N and 10 mm, respectively.
      The platform was also able to estimate the dynamic behavior of a known resistant
      force with an error of 5.45%. Finally, an in vivo experiment on a porcine colon
      model validated the feasibility of measuring the resistant force in opposition to
      magnetic propulsion of a wireless capsule. 

PMID- 24852811
TI  - Improving nutrition in Afghanistan through a community-based growth monitoring
      and promotion programme: a pre-post evaluation in five districts.
AB  - In Afghanistan, malnutrition in children less than 60 months of age remains high
      despite nutritional services being offered in health facilities since 2003.
      Afghanistan's Ministry of Public Health solicited extensive community
      consultation to develop pictorial community-based growth monitoring and promotion
      (cGMP) tools to help illiterate community health workers (CHWs) provide
      nutritional assessment and counselling. The planned evaluation in the five
      districts where cGMP was implemented demonstrated that a mean weight-for-age
      (WFA) Z-score of 414 participant children was 0.3 Z-scores higher than that of
      matched non-participants who lived outside of cGMP programme catchment areas. The
      mean change in WFA Z-scores at evaluation was 0.3 (95% CI 0.3, 0.4) Z-scores
      higher than at entry into the programme. The most influential factor on WFA Z
      score changes in participants was initial WFA Z-score. Those with an initial WFA
      Z-score of less than -2 experienced a mean increase of 0.33 (95% CI 0.29, 0.38)
      WFA Z-scores per session attended, while those with a baseline WFA Z-score of
      greater than zero showed a decrease of 0.19 (95% CI 0.22, 0.15) WFA Z-scores per
      session attended. These results are encouraging since they demonstrate that the
      cGMP programme in Afghanistan for illiterate women has some potential to
      contribute to improving nutrition, specifically in underweight children of either
      sex who enter the programme at less than nine months of age and attend 50% or
      more sessions. 

PMID- 24852812
TI  - Two-year changes in refractive error and related biometric factors in an adult
      Chinese population.
AB  - IMPORTANCE: This article provides, to our knowledge, the first longitudinal
      population-based data on refractive error (RE) in Chinese persons. OBJECTIVE: To
      study cohort effects and changes associated with aging in REs among Chinese
      adults. DESIGN, SETTING, AND PARTICIPANTS: A 2-year, longitudinal population
      based cohort study was conducted in southern China. Participants, identified
      using cluster random sampling, included residents of Yuexiu District, Guangzhou,
      China, aged 35 years or older who had undergone no previous eye surgery. METHODS:
      Participants underwent noncycloplegic automated refraction and keratometry in
      December 2008 and December 2010; in a random 50% sample of the participants,
      anterior segment ocular coherence tomography measurement of lens thickness, as
      well as measurement of axial length and anterior chamber depth by partial
      coherence laser interferometry, were performed. MAIN OUTCOMES AND MEASURES: Two
      year change in spherical equivalent refraction (RE), lens thickness, axial
      length, and anterior chamber depth in the right eye. RESULTS: A total of 745
      individuals underwent biometric testing in both 2008 and 2010 (2008 mean [SD]
      age, 52.2 [11.5] years; 53.7% women). Mean RE showed a 2-year hyperopic shift
      from -0.44 (2.21) to -0.31 (2.26) diopters (D) (difference, +0.13; 95% CI, 0.11
      to 0.16). A consistent 2-year hyperopic shift of 0.09 to 0.22 D was observed
      among participants aged 35 to 64 years when stratifying by decade, suggesting
      that a substantial change in RE with aging may occur during this 30-year period.
      Cross-sectionally, RE increased only in the cohort younger than 50 years (0.11
      D/y; 95% CI, 0.06 to 0.16). In the cross-sectional data, axial length decreased
      at -0.06 mm/y (95% CI, -0.09 to -0.04), although the 2-year change in axial
      length was positive and thus could not explain the cross-sectional difference.
      These latter results suggest a cohort effect, with greater myopia developing
      among younger persons. CONCLUSIONS AND RELEVANCE: This first Chinese population
      based longitudinal study of RE provides evidence for both important longitudinal
      aging changes and cohort effects, most notably greater myopia prevalence among
      younger persons.

PMID- 24852813
TI  - Local recurrence of breast cancer in reconstructed breasts using TRAM flap after
      skin-sparing mastectomy: clinical and imaging features.
AB  - OBJECTIVES: To evaluate clinical and imaging features of cancer recurrence in
      reconstructed breasts following skin-sparing mastectomy (SSM) or nipple areolar
      skin-sparing mastectomy (NASSM). METHODS: This study was approved by our
      Institutional Review Board. In this retrospective study, we included patients
      with pathologically confirmed recurrent cancer who had transverse rectus
      abdominis myocutaneous (TRAM) flap reconstruction after SSM or NASSM and whose
      follow-up radiological studies were available. Each patient's demographic data,
      imaging studies and clinical outcomes were reviewed. Two breast radiologists
      analysed the imaging findings of follow-up mammography, ultrasound and magnetic
      resonance imaging. RESULTS: Of the 964 patients, 16 (1.7%) had local cancer
      recurrence. The average follow-up period until the detection was 31.1 months
      (range, 7-84 months). Fourteen (87.5%) patients had recurrence on the skin or in
      subcutaneous fat. Of the 16 patients, recurrence was detected by breast self
      examination in 13 (81.3%) patients. Eight (50%) lesions mimicked benign lesions.
      The other eight (50%) lesions manifested various degree of suspicion for the
      malignancy. CONCLUSIONS: Recurrent cancer after TRAM flap reconstruction
      following SSM and NASSM is often recognised by breast self-examination and mimics
      imaging findings of benign lesions. Therefore, meticulous physical examination
      and history-taking are important. Pathological confirmation is worthwhile even in
      the benign-appearing lesions. KEY POINTS: Overview of clinical and imaging
      features of cancer recurrence in reconstructed breasts. 50% of recurred malignant
      lesions mimicking imaging findings of benign lesions. Patients may benefit from
      thorough self-breast examination.

PMID- 24852814
TI  - Real-time scrotal ultrasound of patients with varicoceles: correlation with
      impaired semen analysis.
AB  - OBJECTIVES: To evaluate the potential relationship between scrotal ultrasound
      findings and abnormal semen analysis. METHODS: Eighty-seven patients with
      varicoceles underwent semen analysis and scrotal sonography. On ultrasound,
      estimated testes volume and the largest pampiniform vein diameters on the
      affected side at rest and with Valsalva manoeuvre in both the supine and upright
      positions were examined. In addition, the differences between the largest venous
      diameters at rest and during the Valsalva manoeuvre in each position (supine and
      upright) and also the differences between the largest venous diameter in the
      supine position and the upright position in each condition (at rest and during
      the Valsalva manoeuvre) were calculated. The relationship between various
      ultrasound parameters and impaired semen analysis was evaluated using receiver
      operating characteristic curves. RESULTS: Seventy-one patients had
      spermatogenesis impairment, and the remaining 16 had normal semen analysis. The
      difference in the mean spermatic vein diameter at rest between the supine and
      upright positions (cut-off point, 0.25 mm) had the highest diagnostic accuracy in
      differentiating the patients with abnormal sperm analysis from those with normal
      spermatogenesis with an area under the curve of 0.86. CONCLUSIONS: Real-time
      scrotal ultrasound can be helpful in predicting abnormal sperm analysis in
      patients with varicoceles. KEY POINTS: Scrotal ultrasound is a non-invasive
      method to evaluate spermatic veins in varicoceles. Ultrasound can evaluate venous
      dimension change at rest after upright position (DeltaD(R) ). DeltaD( R)  > 2.5
      mm distinguishes patients with abnormal semen analysis. DeltaD( R) has the most
      accuracy in predicting abnormal spermatogenesis. Ultrasound findings improve
      differentiation between patients with abnormal and normal spermatogeneses.

PMID- 24852815
TI  - Interaction between hydrophobically modified 2-hydroxyethyl cellulose and sodium
      dodecyl sulfate studied by viscometry and two-dimensional NOE NMR spectroscopy.
AB  - Interaction between an anionic surfactant, sodium dodecyl sulfate (SDS), and a
      nonionic polymer, 2-hydroxyethyl cellulose (HEC) hydrophobically modified with
      benzoyl chloride (bmHEC), is studied by viscometry and two-dimensional nuclear
      Overhauser effect NMR spectroscopy (2D NOESY) in a semidilute regime of bmHEC.
      The hydrophobicity of bmHEC was varied with different substitution of benzoyl
      group to HEC macromolecules. In general, the low-shear viscosity of 1 wt % bmHEC
      aqueous solution is increased with added SDS surfactant having concentration from
      0 to 0.5 wt %, and then decreased significantly with a further addition of
      surfactant to 3 wt %. The activation energy of transient network formation in 1
      wt % bmHEC aqueous solution present with SDS surfactant is found to be dependent
      with SDS concentration, which varies from 32.7 to 69.80 kJ/mol. The maximum
      activation energy takes place when 0.5 wt % SDS is added, which coincides with
      that of the maximal viscosity. The 2D NOESY displays that the surfactants
      actually interact with bmHEC not only on the hydrophobes, namely benzoyl groups,
      but also the polymer backbone, i.e., glucose units. In contrast, no interaction
      is revealed by 2D NOESY in the aqueous system containing SDS surfactant and HEC
      polymer. 

PMID- 24852816
TI  - Theorizing the relationship between NGOs and the state in medical humanitarian
      development projects.
AB  - Social scientists have fiercely debated the relationship between non-governmental
      organizations (NGOs) and the state in NGO-led development projects. However, this
      research often carries an implicit, and often explicit, anti-state bias,
      suggesting that when NGOs collaborate with states, they cease to be a progressive
      force. This literature thus fails to recognize the state as a complex,
      heterogeneous, and fragmented entity. In particular, the unique political context
      within which an NGO operates is likely to influence how it carries out its work.
      In this article, we ask: how do NGOs work and build relationships with different
      types of states and--of particular relevance to practitioners--what kinds of
      relationship building lead to more successful development outcomes on the ground?
      Drawing on 29 in-depth interviews with members of Partners in Health and Oxfam
      America conducted between September 2010 and February 2014, we argue that NGOs
      and their medical humanitarian projects are more likely to succeed when they
      adjust how they interact with different types of states through processes of
      interest harmonization and negotiation. We offer a theoretical model for
      understanding how these processes occur across organizational fields.
      Specifically, we utilize field overlap theory to illuminate how successful
      outcomes depend on NGOs' ability to leverage resources--alliances and networks;
      political, financial, and cultural resources; and frames--across state and non
      state fields. By identifying how NGOs can increase the likelihood of project
      success, our research should be of interest to activists, practitioners, and
      scholars.

PMID- 24852817
TI  - Surface and intramural reentrant patterns during atrial fibrillation in the
      sheep.
AB  - INTRODUCTION: This article is part of the Focus Theme of Methods of Information
      in Medicine on "Biosignal Interpretation: Advanced Methods for Studying
      Cardiovascular and Respiratory Systems". BACKGROUND: Atrial fibrillation (AF) is
      the most common sustained cardiac arrhythmia in humans and is predicted to
      dramatically increase its prevalence in the future. High-resolution mapping data
      and Fourier power spectral analysis with its dominant frequency support the
      hypothesis that AF in the structurally normal sheep heart and in some patients
      often presents organized drivers in the form of periodic surface re-entries or
      breakthroughs. Nevertheless, the dynamics of those surface patterns of activity,
      as well as their intramural components are still poorly understood. OBJECTIVE: To
      present data on AF waves from the surface of isolated sheep hearts and discuss
      the interpretation of their intramural patterns. METHODS: We used a combination
      of endocardial-epicardial optical mapping with phase and spectral analysis as
      well as computer simulation of the re-entrant activity in the myocardial wall.
      RESULTS: Analysis of the surfaces' optical mapping data in the phase domain
      reveals that activation of the posterior left atrium (PLA) consisted of
      alternating patterns of breakthroughs and reentries. The patterns on the
      endocardial and epicardial PLA surface at any given moment of time of the AF
      could be either identical or not identical, and the activity in the thickness of
      the PLA wall is hypothesized to conform to either ectopic discharge or reentrant
      scroll waves, but a definite evidence for the presence of such mechanisms is
      currently lacking. A universal minimal-principle theory is shown in a computer
      model to result in a tendency of the axis of the scroll waves to align with the
      myocardial fibers inside the wall. CONCLUSION: The tendency of filaments of
      scroll waves to align with myocardial fibers may contribute to the variety and
      intermittency of surface rotors seen in AF.

PMID- 24852819
TI  - Variability of seed traits and properties of soluble mucilages in lines of the
      flax genetic collection of Vavilov Institute.
AB  - Upon hydration, flax seeds secrete mucilages whose content and physico-chemical
      properties vary according to the genotype and environment. The aim of the work
      was to investigate the complex genetic relationships between the vegetative
      period, colour, size and production of seed, the composition (polysaccharides and
      proteins) and physico-chemical properties of soluble mucilages collected at 28 
      degrees C from seeds of 18 lines grown in St Petersburg area. The vegetative
      period duration was found to impact the size and production of seeds, the yield
      of mucilages, including the polysaccharides, and the galactosidase enzymes, as
      well as their composition (mainly the rhamnogalacturonan I moieties) and some of
      their properties (mainly viscosity). Data allowed to significantly distinguish 6
      fibre lines with mucilages enriched in rhamnogalacturonan I, 6 lines with
      mucilages enriched in arabinoxylan including 5 linseeds and 1 mutated fibre-line,
      and 5 lines with mucilages enriched in homogalacturonan-like polymer including 4
      fibre lines and 1 brown linseed. Seven fibre lines had mucilages particularly
      rich in galactose. High to very high variability was found for 14 traits.
      Relatively independent characters (form/shape, protein and galactosidase) were
      identified and could be combined by breeding, with a focus on mucilage yield,
      composition and properties. Main-component analyses of line characters showed a
      large diversity in linseeds mainly due to their different origin but small
      variation in Russian fibre lines with brown seeds.

PMID- 24852820
TI  - Adverse skin reactions during treatment with cetuximab plus radiotherapy:
      Multidisciplinary approach to minimize radio-chemotherapy interruption.
AB  - BACKGROUND: Antibodies against the epidermal growth factor receptor (EGFR), such
      as cetuximab, are effective in loco-regional advanced squamous cell carcinoma of
      the head and neck (SCCHN) in association with radiotherapy. Cutaneous reactions
      are well known as adverse events during treatment with EGFR inhibitors.
      OBJECTIVE: To identify a multidisciplinary approach for mucous-cutaneous toxicity
      during cetuximab-radiotherapy treatment in order to reduce the risk of an early
      radio-chemotherapy interruption. METHODS: The data of 38 patients with SCCHN
      receiving cetuximab and radiotherapy were retrospectively analyzed. The control
      group (n = 15) received the standardized treatments according to the severity of
      skin reactions with dermatologic visits only for high degrees of toxicity. The
      experimental group (n = 23) was monitored and daily treated by dermatologists
      since grade 1 of cutaneous toxicity. The primary end-point of our study was the
      mean days of antitumor therapy interruption. RESULTS: The mean number of days of
      antitumor therapy suspension was 12.6 (7.6) in the standard treatment group and
      5.0 (6.6) in the experimental group (p = 0.002). This difference was observed for
      each grade of toxicity. CONCLUSION: The early interruption of radio-chemotherapy
      has a negative impact on survival in patients with SCCHN. In our study, a closer
      dermatological examination and treatment for all degrees of toxicity reduced
      early interruptions of chemo-radiotherapy.

PMID- 24852821
TI  - Does switching from oral to subcutaneous administration of methotrexate influence
      on patient reported gastro-intestinal adverse effects?
AB  - INTRODUCTION: When treating patients with methotrexate (MTX) the most frequently
      reported adverse effects (AE) are gastrointestinal (GI) with nausea being
      reported by 10-20%. If intolerable AE of oral MTX persist, switching from oral to
      subcutaneous (SC) or intramuscular (IM) administration is common. However, this
      approach is largely empirical and the evidence is inconsistent. To our knowledge,
      this will be the first study to estimate the change in GI AE of switching from
      oral to SC MTX. METHODS: A retrospective postal survey was sent to patients who
      had changed from oral MTX to SC MTX. GI AE was rated by visual analogue scale
      (VAS) regarding frequency and intensity of nausea, frequency of vomiting and
      frequency of discomfort. All participants gave informed consent. No further
      ethical clearance was necessary according to national law. RESULTS: Of the sample
      39/57 (68.4%) responded. Significant reductions in VAS were found in three of
      four primary outcome measures for GI AE. Only frequency of vomiting was not
      significantly reduced. CONCLUSION: Our findings support the common practice of
      switching from oral to SC MTX to alleviate GI AE, however, additional research is
      needed in order to clarify this rarely studied subject.

PMID- 24852818
TI  - Heterology expression of the tomato LeLhcb2 gene confers elevated tolerance to
      chilling stress in transgenic tobacco.
AB  - Chilling is one of the most serious environmental stresses that disrupt the
      metabolic balance of cells and enhance the production of reactive oxygen species
      (ROS). Light harvesting complex (LHC) proteins had a function in dissipating
      excess excitation energy and eliminating ROS to maintain the normal physiological
      function of cells. A tomato (Lycopersicon esculentum) LHC antenna protein gene
      (LeLhcb2) was isolated. The LeLhcb2-green fluorescent protein (GFP) fusion
      protein was targeted to the chloroplast of Arabidopsis mesophyll protoplast.
      Quantitative real-time polymerase chain reaction (qRT-PCR) analysis indicated
      that the expression of LeLhcb2 was markedly abundant in leaves and was induced by
      chilling (4  degrees C). qRT-PCR analysis and western blot confirmed that the
      sense gene LeLhcb2 was transferred into tobacco genome and overexpressed. Under
      chilling stress, the transgenic plants showed not only better growth, higher
      fresh weight, chlorophyll content, but also lower malondialdehyde (MDA)
      accumulation and relative electrical conductivity (REC), compared with the wild
      type (WT). The maximal photochemical efficiency of PSII (Fv/Fm), non
      photochemical quenching (NPQ) and D1 protein content were also higher in the
      transgenic plants. Furthermore, the relatively lower hydrogen peroxide (H2O2) and
      superoxide radical (O2(-)) levels in the sense plants were not considered to due
      to the higher activity of ascorbate peroxidase (APX) and superoxide dismutase
      (SOD). These results suggested that the overexpression of LeLhcb2 had a key
      function in alleviating photo-oxidation of PSII and enhanced transgenic tobacco
      tolerance to chilling stress.

PMID- 24852822
TI  - High energy conformers of M(+)(APE)(H2O)(0-1)Ar(0-1) clusters revealed by
      combined IR-PD and DFT-MD anharmonic vibrational spectroscopy.
AB  - IR-PD vibrational spectroscopy and DFT-based molecular dynamics simulations are
      combined in order to unravel the structures of M(+)(APE)(H2O)0-1 ionic clusters
      (M = Na, K), where APE (2-amino-1-phenyl ethanol) is commonly used as an analogue
      for the noradrenaline neurotransmitter. The strength of the synergy between
      experiments and simulations presented here is that DFT-MD provides anharmonic
      vibrational spectra that unambiguously help assign the ionic clusters structures.
      Depending on the interacting cation, we have found that the lowest energy
      conformers of K(+)(APE)(H2O)0-1 clusters are formed, while the lowest energy
      conformers of Na(+)(APE)(H2O)0-1 clusters can only be observed through water loss
      channel (i.e. without argon tagged to the clusters). Trapping of higher energy
      conformers is observed when the argon loss channel is recorded in the experiment.
      This has been rationalized by transition state energies. The dynamical anharmonic
      vibrational spectra unambiguously provide the prominent OH stretch due to the
      OH...NH2 H-bond, within 10 cm(-1) of the experiment, hence reproducing the 240
      300 cm(-1) red-shift (depending on the interacting cation) from bare neutral APE.
      When this H-bond is not present, the dynamical anharmonic spectra provide the
      water O-H stretches as well as the rotational motion of the water molecule at
      finite temperature, as observed in the experiment.

PMID- 24852823
TI  - Higher levels of antibodies to the tumour-associated antigen cyclin B1 in cancer
      free individuals than in patients with breast cancer.
AB  - Cyclin B1 is a checkpoint protein that regulates cell division from G2 to the M
      phase. Studies in mice have shown that cyclin B1 vaccine-induced immunity
      significantly delayed or prevented the spontaneous cancer development later in
      life. We hypothesized that if these results showing a protective effect of anti
      cyclin B1 antibodies could be extrapolated to the human condition, cancer-free
      individuals should have higher levels of endogenous antibodies than patients with
      cancers characterized by the over-expression of this tumour-associated antigen.
      To test this hypothesis, we characterized a large (1739 subjects) number of multi
      ethnic patients with breast cancer (which over-expresses cyclin B1) and matched
      controls for anti-cyclin B1 immunoglobulin (Ig)G antibodies. Multivariate
      analyses, after adjusting for the covariates, showed that cancer-free individuals
      had significantly higher levels of naturally occurring IgG antibodies to cyclin
      B1 than patients with breast cancer (mean +/- standard deviation: 148.0 +/- 73.6
      versus 126.1 +/- 67.8 arbitrary units per ml; P < 0.0001). These findings may
      have important implications for cyclin B1-based immunotherapy against breast
      cancer and many other cyclin B1-over-expressing malignancies.

PMID- 24852824
TI  - Developmental trajectories of verbal and visuospatial abilities in healthy older
      adults: comparison of the hemisphere asymmetry reduction in older adults model
      and the right hemi-ageing model.
AB  - Two models of cognitive ageing, the hemisphere asymmetry reduction in older
      adults (HAROLD) model and the right hemi-ageing model, were compared based upon
      the verbal memory and visuospatial task performance of 338 elderly participants.
      Comparison of the developmental trajectories for four age groups (50s, 60s, 70s
      and 80s) supported the HAROLD model, but not the right hemi-ageing model.
      Performance differences between the verbal memory and visuospatial tasks in the
      earlier age groups decreased in the later age groups. There was a sex difference
      in the cognitive-decline trajectories for verbal and visuospatial task
      performance after the 50s. 

PMID- 24852825
TI  - Re: 'Cradle cap' in puppies.

PMID- 24852827
TI  - Theta-burst stimulation induces LTP at excitatory and inhibitory synapses in the
      spinal trigeminal subnucleus interpolaris.
AB  - Long-lasting synaptic modifications of excitatory and inhibitory synaptic
      transmissions induced by theta-burst stimulation (TBS) were examined in the
      spinal trigeminal subnucleus interpolaris (Vi). We found that conditioning
      afferents of another subnucleus caudalis (Vc) to the Vi with TBS produced long
      term depression (LTD). However, when GABAA and glycine receptors were blocked,
      the same stimulation paradigm produced long-term potentiation (LTP). The
      induction of LTP involved neither NMDA receptors nor a presynaptic change. The
      expression of LTP was obviously suppressed by the activation of group I mGluRs
      because its magnitude increased in the presence of antagonists for group I
      mGluRs. Besides the LTP at excitatory synapses, TBS also induced LTP at
      inhibitory GABAergic synapses, which required the activation of NMDA receptors
      and NO-cGMP signaling but was not involved in the increase of postsynaptic Ca(2+)
      concentration. Therefore, this study shows, for the first time, an activity
      dependent plasticity at excitatory and inhibitory synapses in the Vi by the same
      conditioning stimulation. 

PMID- 24852826
TI  - Six homeoproteins and a Iinc-RNA at the fast MYH locus lock fast myofiber
      terminal phenotype.
AB  - Thousands of long intergenic non-coding RNAs (lincRNAs) are encoded by the
      mammalian genome. However, the function of most of these lincRNAs has not been
      identified in vivo. Here, we demonstrate a role for a novel lincRNA, linc-MYH, in
      adult fast-type myofiber specialization. Fast myosin heavy chain (MYH) genes and
      linc-MYH share a common enhancer, located in the fast MYH gene locus and
      regulated by Six1 homeoproteins. linc-MYH in nuclei of fast-type myofibers
      prevents slow-type and enhances fast-type gene expression. Functional fast
      sarcomeric unit formation is achieved by the coordinate expression of fast MYHs
      and linc-MYH, under the control of a common Six-bound enhancer. 

PMID- 24852828
TI  - Impairment of attention networks in patients with untreated hyperthyroidism.
AB  - Attention disorders are common symptoms in patients with untreated
      hyperthyroidism. Nevertheless, it is unknown whether they represent a global
      attention deficit or selective impairment of attention networks. Thirty-seven
      patients with hyperthyroidism were recruited and underwent the Attention Network
      Test (ANT), which provided measures of three independent attention networks
      (alerting, orienting and executive control), before being treated with
      methimazole. This study demonstrated that patients with untreated hyperthyroidism
      had significant deficits in the alerting and executive control networks.
      Interestingly, a significant positive association was also found between T4 level
      and the value of the executive network in patients with hyperthyroidism. These
      results suggest that the patients with hyperthyroidism may not just exist a
      specific impairment of attention networks, and there was some relationship
      between the level of T4, not T3 or TSH, and the value of the executive control
      network in patients with hyperthyroidism. 

PMID- 24852829
TI  - The association of single nucleotide polymorphism of the Fyn gene with sporadic
      Alzheimer's disease in the Chinese Han population.
AB  - Recent studies suggested genetic factors contribute to the pathogenesis of
      sporadic Alzheimer's disease (sAD). Fibroblast Yes related novel (Fyn), a tau
      kinase, has been reported to be associated with aberrant phosphorylated tau and
      neurofibrillary tangles formation. Fyn gene may be a potential candidate gene for
      AD. To investigate the association of the polymorphisms in Fyn gene with the
      susceptibility to sAD, we conducted a case-control study in a Chinese Han cohort
      including 200 sAD patients and 243 control participants. Four single nucleotide
      polymorphisms (SNPs) (rs111787668, rs1057979, rs6916861 and rs12910) within the
      promoter region of Fyn gene and one (rs7768046) in intron were selected and
      genotyped with a polymerase chain reaction-ligase detection reaction (PCR-LDR)
      method. Logistic regression under four genetic models was used to analyze the
      association between target SNPs and the risk of sAD. After adjusting for age, sex
      and APOE E4 status, no association was revealed between these SNPs or the
      haplotypes containing four SNPs and the risk of sAD (P>0.05). The SNPs in the
      selected regions of the Fyn gene are unlikely to confer the susceptibility of sAD
      in the Chinese Han population. Further studies with a larger sample size and
      different ethnic populations are needed to reveal the role of Fyn gene in the
      pathogenesis of sAD. 

PMID- 24852830
TI  - Perioperative hypertensive emergencies.
AB  - The concept of "perioperative hypertensive emergency" must be defined differently
      from that of ambulatory hypertensive emergency in view of its unique clinical
      considerations in an atypical setting. It should be noted that moderately high
      normal blood pressure (BP) values in the perioperative setting often trigger
      situations requiring immediate treatment in what would otherwise be a "BP
      acceptable" non-surgical condition. Commonly recognized circumstances that may
      result in a perioperative hypertensive emergency include exacerbation of severe
      mitral insufficiency, hypertension resulting in acute decompensated heart
      failure, hypertension caused by acute catecholamine excess, rebound hypertension
      after withdrawal of antihypertensive medications, hypertension resulting in
      bleeding from vascular surgery suture lines, intracerebral hemorrhage, aortic
      dissection, hypertension associated with preeclampsia, and hypertension
      associated with autonomic dysreflexia. In addition, perioperative BP lability has
      been reported to increase the risk for stroke, acute kidney injury, and 30-day
      mortality in patients undergoing cardiac surgery.

PMID- 24852831
TI  - 'Olympic' centenarians: are they just biologically exceptional?

PMID- 24852832
TI  - Use of covered Cheatham-Platinum stents in congenital heart disease.
AB  - BACKGROUND: Controversy remains regarding the use of covered stents in congenital
      heart disease (CHD). We evaluate the possibilities and safety of covered Cheatham
      Platinum (CCP) stents in CHD. METHODS: Single-center retrospective CHD-database
      study of all CCP stents, 2003-2012. Three study groups: aortic coarctation (CoA),
      right ventricular outflow tract pre-stenting for percutaneous revalvulation
      (RVOT), and miscellaneous. Continuous data expressed as median (range). RESULTS:
      114 CCP stents in 105 patients, age 16.8 years (4.2-71.2). CoA group: 54 CCP
      stents in 51 patients: 3/54 for aneurysm exclusion, in 51/54 covering used
      "prophylactically" because of increased risk for vessel tear. Overall, CCP
      stenting increased the coarctation diameter from 6mm (0-15) to 15 mm (10-20)
      (p<0.001). RVOT group: 39 CCP stents in 37 patients (34 with RVOT graft, 3 with
      transannular patch): the graft lumen had shrunken from nominal 21 mm (10-26) to
      13 mm (5-22); with the CCP stent the RVOT was redilated to 22 mm (16-26, p<0.001
      vs stenosis). Miscellaneous group: 21 CCP stents in 17 patients: closure of
      Fontan-circuit fenestration (n=5), restoration of superior caval vein (n=2) or
      pulmonary artery (n=3) patency, relief of supra-pulmonary stenosis (n=2),
      exclusion of aberrant pulmonary arteries (n=1), cavopulmonary conduit expansion
      (n=2), Blalock-Taussig shunt flow reduction (n=1), and defibrillator lead
      protection from sharp stents (n=1). Hybrid procedures performed in 3/17 patients.
      CCP stent was used as rescue treatment in 2/patients to seal iatrogenic bleeding.
      CONCLUSION: CCP stents can safely be applied in CHD patients. The covering allows
      adequate sealing of existing or expected tears, thereby increasing the safety
      margin with more complete dilation.

PMID- 24852833
TI  - Anti-hypertrophic effects of oxytocin in rat ventricular myocytes.
AB  - BACKGROUND: Oxytocin (OT) and functional OT receptor (OTR) are expressed in the
      heart and are involved in blood pressure regulation and cardioprotection. Cardiac
      OTR signaling is associated with atrial natriuretic peptide (ANP) and nitric
      oxide (NO) release. During the synthesis of OT, its precursor, termed OT-Gly-Lys
      Arg (OT-GKR), is accumulated in the developing rat heart. Consequently, we
      hypothesized that an OT-related mechanism of ANP controls cardiomyocyte (CM)
      hypertrophy. METHODS: The experiments were carried out in newborn and adult rat
      CM cultures. The enhanced protein synthesis and increased CM volume were mediated
      by a 24-h treatment with endothelin-1 or angiotensin II. RESULTS: The treatment
      of CM with OT or its abundant cardiac precursor, OT-GKR, revealed ANP
      accumulation in the cell peri-nuclear region and increased intracellular cGMP.
      Consequently, the CM hypertrophy was abolished by the treatment of 10nM OT or
      10nM OT-GKR. The ANP receptor antagonist (anantin) and NO synthases inhibitor (l
      NAME) inhibited cGMP production in CMs exposed to OT. STO-609 and compound C
      inhibition of anti-hypertrophic OT effects in CMs indicated the contribution of
      calcium-calmodulin kinase kinase and AMP-activated protein kinase pathways.
      Moreover, in ET-1 stimulated cells, OT treatment normalized the reduced Akt
      phosphorylation, prevented abundant accumulation of ANP and blocked ET-1-mediated
      translocation of nuclear factor of activated T-cells (NFAT) into the cell nuclei.
      CONCLUSION: cGMP/protein kinase G mediates OT-induced anti-hypertrophic response
      with the contribution of ANP and NO. OT treatment represents a novel approach in
      attenuation of cardiac hypertrophy during development and cardiac pathology.

PMID- 24852834
TI  - Coronary fistula of the left main artery draining in the right atrium and
      associated aorto-right atrial fistula.

PMID- 24852835
TI  - Impact of hypertension on clinical outcome in STEMI patients undergoing primary
      angioplasty with BMS or DES: insights from the DESERT cooperation.
AB  - BACKGROUND: Hypertension is a well known risk factor for atherosclerosis.
      However, data on the prognostic impact of hypertension in patients with ST
      elevation myocardial infarction (STEMI) are inconsistent and mainly related to
      studies performed in the thrombolytic era, with very few data in patients
      undergoing primary angioplasty. Therefore, the aim of the current study was to
      evaluate the impact hypertension on clinical outcome in STEMI patients undergoing
      primary PCI with BMS or DES. METHODS: Our population is represented by 6298 STEMI
      patients undergoing primary angioplasty included in the DESERT database from 11
      randomized trials comparing DES vs BMS for STEMI. RESULTS: Hypertension was
      observed in 2764 patients (43.9%), and associated with ageing (p<0.0001), female
      gender (p<0.001), diabetes (p<0.0001), hypercholesterolemia (p<0.0001), previous
      MI (p=0.002), previous revascularization (p=0.002), longer time-to-treatment
      (p<0.001), preprocedural TIMI 3 flow, and with a lower prevalence of smoking (41%
      vs 53.9%, p<0.001) and anterior MI (42% vs 45.9%, p=0.002). Hypertension was
      associated with impaired postprocedural TIMI 0-2 flow (Adjusted OR [95% CI]=1.22
      [1.01-1.47], p=0.034). At a follow-up of 1,201 +/- 440 days, hypertension was
      associated with higher mortality (adjusted HR [95% CI]=1.24 [1.01-1.54],
      p=0.048), reinfarction (adjusted HR [95% CI]=1.31 [1.03-1.66], p=0.027), stent
      thrombosis (adjusted HR [95% CI]=1.29 [0.98-1.71], p=0.068) and TVR (adjusted HR
      [95% CI]=1.22 [1.04-1.44], p=0.013). CONCLUSIONS: This study showed that among
      STEMI patients undergoing primary angioplasty with DES or BMS, hypertension is
      independently associated with impaired epicardial reperfusion, mortality,
      reinfarction and TVR, and a trend in higher ST.

PMID- 24852836
TI  - Feature-tracking cardiovascular magnetic resonance as a novel technique for the
      assessment of mechanical dyssynchrony.
AB  - BACKGROUND: Myocardial tagging using cardiovascular magnetic resonance (CMR) is
      the gold-standard for the assessment of myocardial mechanics. Feature-tracking
      cardiovascular magnetic resonance (FT-CMR) has been validated against myocardial
      tagging. We explore the potential of FT-CMR in the assessment of mechanical
      dyssynchrony, with reference to patients with cardiomyopathy and healthy
      controls. METHODS: Healthy controls (n=55, age: 42.9 +/- 13 yrs, LVEF: 70 +/- 5%,
      QRS: 88 +/- 9 ms) and patients with cardiomyopathy (n=108, age: 64.7 +/- 12 yrs,
      LVEF: 29 +/- 6%, QRS: 147 +/- 29 ms) underwent FT-CMR for the assessment of the
      circumferential (CURE) and radial (RURE) uniformity ratio estimate based on
      myocardial strain (both CURE and RURE: 0 to 1; 1=perfect synchrony) RESULTS: CURE
      (0.79 +/- 0.14 vs. 0.97 +/- 0.02) and RURE (0.71 +/- 0.14 vs. 0.91 +/- 0.04) were
      lower in patients with cardiomyopathy than in healthy controls (both p<0.0001).
      CURE (area under the receiver-operator characteristic curve [AUC]: 0.96), RURE
      (AUC: 0.96) and an average of these (CURE:RUREAVG, AUC: 0.98) had an excellent
      ability to discriminate between patients with cardiomyopathy and controls
      (sensitivity 90%; specificity 98% at a cut-off of 0.89). The time taken for semi
      automatically tracking myocardial borders was 5.9 +/- 1.4 min. CONCLUSION:
      Dyssynchrony measures derived from FT-CMR, such as CURE and RURE, provide almost
      absolute discrimination between patients with cardiomyopathy and healthy
      controls. The rapid acquisition of these measures, which does not require
      specialized CMR sequences, has potential for the assessment of mechanical
      dyssynchrony in clinical practice.

PMID- 24852837
TI  - Trend in the use of drug eluting stents in the United States: insight from over
      8.1 million coronary interventions.
AB  - BACKGROUND: Drug eluting stents (DES) reduce the risk of restenosis but are
      associated with increase in the risk of very late stent thrombosis, especially
      when antiplatelet therapy is held. The trend in DES use across the US is not
      fully defined. METHODS: Data from the 2001-2011 Nationwide Inpatient Sample for
      patients undergoing PCI were used. The trend in DES use was analyzed overall and
      in subgroups at risk of restenosis (those with diabetes, chronic kidney disease
      or prior PCI), stent thrombosis (those with acute coronary syndrome) or bleeding
      (those with history of bleeding peptic ulcer or atrial fibrillation). RESULTS:
      Among the 8,150,763 PCI procedures performed, DES use peaked in 2005 at 89% in
      all patients including groups with a low risk of restenosis, high risk of stent
      thrombosis or bleeding. A steep drop to 66% was noted in 2007 followed by a
      progressive rise to 73% in 2011 (P<0.0001). The 2011 DES use patterns indicate
      increased DES use in subgroups at risk of restenosis, decreased use in subgroups
      at risk of thrombosis or bleeding but also lower use in groups at risk for
      discriminant care such as African Americans, the elderly and patients with
      Medicaid/self-pay. CONCLUSIONS: DES trends indicate rapid and broad initial use
      followed by a sharp decline in 2007 and a progressive rise in 2011. DES use in
      2011 seemed based on risk category, but was lower in groups at risk for
      discriminant care.

PMID- 24852839
TI  - Incidence of sudden cardiac death in congestive heart failure: Chagas disease
      versus systemic arterial hypertension.

PMID- 24852841
TI  - Transient parkinsonism after unilateral midbrain stroke: a compensatory
      intervention from the healthy side?

PMID- 24852840
TI  - Atopic myelitis is not restricted to Japanese patients.

PMID- 24852842
TI  - Functional improvement and maturation of rat and human engineered heart tissue by
      chronic electrical stimulation.
AB  - Spontaneously beating engineered heart tissue (EHT) represents an advanced in
      vitro model for drug testing and disease modeling, but cardiomyocytes in EHTs are
      less mature and generate lower forces than in the adult heart. We devised a novel
      pacing system integrated in a setup for videooptical recording of EHT contractile
      function over time and investigated whether sustained electrical field
      stimulation improved EHT properties. EHTs were generated from neonatal rat heart
      cells (rEHT, n=96) or human induced pluripotent stem cell (hiPSC)-derived
      cardiomyocytes (hEHT, n=19). Pacing with biphasic pulses was initiated on day 4
      of culture. REHT continuously paced for 16-18 days at 0.5Hz developed 2.2* higher
      forces than nonstimulated rEHT. This was reflected by higher cardiomyocyte
      density in the center of EHTs, increased connexin-43 abundance as investigated by
      two-photon microscopy and remarkably improved sarcomere ultrastructure including
      regular M-bands. Further signs of tissue maturation include a rightward shift (to
      more physiological values) of the Ca(2+)-response curve, increased force response
      to isoprenaline and decreased spontaneous beating activity. Human EHTs stimulated
      at 2Hz in the first week and 1.5Hz thereafter developed 1.5* higher forces than
      nonstimulated hEHT on day 14, an ameliorated muscular network of longitudinally
      oriented cardiomyocytes and a higher cytoplasm-to-nucleus ratio. Taken together,
      continuous pacing improved structural and functional properties of rEHTs and
      hEHTs to an unprecedented level. Electrical stimulation appears to be an
      important step toward the generation of fully mature EHT. 

PMID- 24852844
TI  - Cellulose-acetate electrophoresis reveals haemoglobin variation in Iranian
      domestic shorthaired cats.

PMID- 24852843
TI  - Adiponectin regulates SR Ca(2+) cycling following ischemia/reperfusion via
      sphingosine 1-phosphate-CaMKII signaling in mice.
AB  - The adipocyte-secreted hormone adiponectin (APN) exerts protective effects on the
      heart under stress conditions. Recent studies have demonstrated that APN induces
      a marked Ca(2+) influx in skeletal muscle. However, whether APN modulates
      [Ca(2+)]i activity, especially [Ca(2+)]i transients in cardiomyocytes, is still
      unknown. This study was designed to determine whether APN modulates [Ca(2+)]i
      transients in cardiomyocytes. Adult male wild-type (WT) and APN knockout (APN KO)
      mice were subjected to myocardial ischemia/reperfusion (I/R, 30min/30min) injury.
      CaMKII-PLB phosphorylation and SR Ca(2+)-ATPase (SERCA2) activity were
      downregulated in I/R hearts of WT mice and further decreased in those of APN KO
      mice. Both the globular domain of APN and full-length APN significantly reversed
      the decrease in CaMKII-PLB phosphorylation and SERCA2 activity in WT and APN KO
      mice. Interestingly, compared with WT littermates, single myocytes isolated from
      APN KO mice had remarkably decreased [Ca(2+)]i transients, cell shortening, and a
      prolonged Ca(2+) decay rate. Further examination revealed that APN enhances
      SERCA2 activity via CaMKII-PLB signaling. In in vivo and in vitro experiments,
      both APN receptor 1/2 and S1P were necessary for the APN-stimulated CaMKII-PLB
      SERCA2 activation. In addition, S1P activated CaMKII-PLB signaling in neonatal
      cardiomyocytes in a dose dependent manner and improved [Ca(2+)]i transients in
      APN KO myocytes via the S1P receptor (S1PR1/3). Further in vivo experiments
      revealed that pharmacological inhibition of S1PR1/3 and SERCA2 siRNA suppressed
      APN-mediated cardioprotection during I/R. These data demonstrate that S1P is a
      novel regulator of SERCA2 that activates CaMKII-PLB signaling and mediates APN
      induced cardioprotection. 

PMID- 24852838
TI  - Valve surgery in active infective endocarditis: a simple score to predict in
      hospital prognosis.
AB  - AIMS: Surgery for infective endocarditis (IE) is associated with high mortality.
      Our objectives were to describe the experience with surgical treatment for IE in
      Spain, and to identify predictors of in-hospital mortality. METHODS: Prospective
      cohort of 1000 consecutive patients with IE. Data were collected in 26 Spanish
      hospitals. RESULTS: Surgery was performed in 437 patients (43.7%). Patients
      treated with surgery were younger and predominantly male. They presented fewer
      comorbid conditions and more often had negative blood cultures and heart failure.
      In-hospital mortality after surgery was lower than in the medical therapy group
      (24.3 vs 30.7%, p=0.02). In patients treated with surgery, endocarditis involved
      a native valve in 267 patients (61.1%), a prosthetic valve in 122 (27.9%), and a
      pacemaker lead with no clear further valve involvement in 48 (11.0%). The most
      common aetiologies were Staphylococcus (186, 42.6%), Streptococcus (97, 22.2%),
      and Enterococcus (49, 11.2%). The main indications for surgery were heart failure
      and severe valve regurgitation. A risk score for in-hospital mortality was
      developed using 7 prognostic variables with a similar predictive value (OR
      between 1.7 and 2.3): PALSUSE: prosthetic valve, age >= 70, large intracardiac
      destruction, Staphylococcus spp, urgent surgery, sex [female], EuroSCORE >= 10.
      In-hospital mortality ranged from 0% in patients with a PALSUSE score of 0 to
      45.4% in patients with PALSUSE score >3. CONCLUSIONS: The prognosis of IE surgery
      is highly variable. The PALSUSE score could help to identify patients with higher
      in-hospital mortality.

PMID- 24852845
TI  - Angiostrongylus vasorum in Great Britain: a nationwide postal questionnaire
      survey of veterinary practices.
AB  - The lungworm, Angiostrongylus vasorum, was first reported in indigenous dogs in
      southwestern England in 1980 and has since been recorded in Wales, southeastern
      England and, more recently, in the West Midlands, northern England and Scotland.
      The nationwide distribution of the parasite was evaluated using a postal
      questionnaire sent to 3950 small animal practices during 2009. Information was
      sought on the location of each practice, awareness of the parasite locally,
      number of cases diagnosed over the past year and whether diagnosis was based on
      clinical signs alone or supported by additional tests. 1419 practices returned a
      usable response, the majority being located in a city/town. Nearly one-third of
      responding practices were aware of the parasite locally, 20.7 per cent had seen
      at least one confirmed case and 0.3 per cent >20 confirmed cases over the past
      year. The most widely used tests were faecal examination and any type of imaging.
      Existing clusters of infection were detected in southeastern England and south
      Wales; infection was also found to be widespread in central England, though
      patchy in northern England and Scotland. Using distribution of clinical cases as
      an indicator of parasite distribution, this study confirmed that A. vasorum has
      spread beyond traditional UK endemic foci. 

PMID- 24852846
TI  - The association of osteocalcin and adiponectin with glucose metabolism in
      nondiabetic postmenopausal women.
AB  - BACKGROUND/AIM: This study was designed to determine if osteocalcin is associated
      with insulin resistance, metabolic risk factors and adiponectin levels in
      nondiabetic postmenopausal women. METHODS: A total of 87 menopausal nondiabetic
      subjects were enrolled into the study. Levels of fasting plasma glucose (FPG),
      insulin and serum lipids were determined. To estimate insulin sensitivity,
      homeostasis model assessment (HOMA-IR) and the quantitative insulin sensitivity
      check index (QUICKI) were used. Serum total osteocalcin and adiponectin levels
      were measured and the features of metabolic syndrome were identified. RESULTS:
      The mean age of the patients was 54.7 years. Among the participants, 28.7% were
      obese (body mass index, BMI, >=30). Insulin resistance was detected by HOMA-IR in
      42.5% and by the QUICKI index in 63.2% of the cases. Metabolic syndrome was
      present in 29.8% of the patients. Neither the baseline characteristics nor the
      metabolic risk factors were correlated with osteocalcin or adiponectin levels (p
      > 0.05). When the patients were analyzed regarding BMI, osteocalcin levels were
      significantly lower in overweight women. Serum adiponectin levels were
      significantly lower in women with metabolic syndrome. CONCLUSION: No correlation
      between total osteocalcin and FPG, fasting insulin and insulin resistance
      parameters was found in nondiabetic postmenopausal women. Serum levels of
      adiponectin were associated with metabolic syndrome.

PMID- 24852847
TI  - Effect of polymer-free TiO2 stent coated with abciximab or alpha lipoic acid in
      porcine coronary restenosis model.
AB  - BACKGROUND: Polymer-free drug-eluting stents (DES) may overcome the shortcomings
      of polymer-based DES. The aim of this study was to examine the effect of the
      polymer-free TiO2 film-coated stent with abciximab or alpha lipoic acid in a
      porcine coronary overstretch restenosis model. METHODS: Pigs were randomized into
      four groups in which the coronary arteries (24 pigs, 48 coronaries in each group)
      had TiO2 film-coated stent with abciximab (TCA, n = 12), TiO2 film-coated stent
      with alpha lipoic acid (TCALA, n = 12), biolimus A9-eluting stents with
      biodegradable polymer (BES, n = 12), and TiO2 film-coated stent (TCstent, n =
      12). Histopathologic analysis was performed at 28 days after stenting. RESULTS:
      There was no significant difference in the injury score and internal elastic
      lamina (IEL) among the four groups. There were significant differences in the
      lumen area, neointima area, percent area stenosis, fibrin score, and inflammation
      score among the four groups [2.7 +/- 1.0mm(2), 2.6 +/- 0.94 mm(2), 48.9 +/-
      16.25%, 1.0 (range 0.0-3.0), 1.0 (range 0.0-2.0) in TCA stent group vs. 2.7 +/-
      1.24 mm(2), 2.9 +/- 0.83 mm(2), 53.5 +/- 17.19%, 1.0 (range 0.0-2.0), 1.0 (range
      0.0-2.0) in TCALA stent group vs. 2.7 +/- 1.30 mm(2), 2.6 +/- 1.06 mm(2), 50.1 +/
      23.20%, 2.0 (range 1.0-3.0), 2.0 (range 1.0-3.0) in BES group vs. 1.7 +/- 0.63
      mm(2), 3.3 +/- 0.58 mm(2), 60.2 +/- 10.12%, 0.5 (range 0.0-2.0), 1.0 (range 0.0
      2.0) in TC stent group, respectively]. CONCLUSION: TCA and TCALA are more
      effective to reduce neointimal hyperplasia compared to TC. Moreover, fibrin and
      inflammation scores are significantly lower in TCA and TCALA than BES in porcine
      coronary restenosis model.

PMID- 24852850
TI  - Defining a therapeutic target for pallidal deep brain stimulation for dystonia.
AB  - OBJECTIVE: To create a data-driven computational model that identifies brain
      regions most frequently influenced by successful deep brain stimulation (DBS) of
      the globus pallidus (GP) for advanced, medication-resistant, generalized
      dystonia. METHODS: We studied a retrospective cohort of 21 DYT1 primary dystonia
      patients treated for at least 1 year with bilateral pallidal DBS. We first
      created individual volume of tissue activation (VTA) models utilizing
      neuroimaging and postoperative stimulation and clinical data. These models were
      then combined into a standardized probabilistic dystonia stimulation atlas (DSA).
      Finally, we constructed a candidate target volume from electrodes demonstrating
      at least 75% improvement in contralateral symptoms, utilizing voxels stimulated
      by least 75% of these electrodes. RESULTS: Pallidal DBS resulted in a median
      contralateral hemibody improvement of 90% (mean = 83%, standard deviation [SD] =
      20) after 1 year of treatment. Individual VTA models of the 42 active electrodes
      included in the study demonstrated a mean stimulation volume of 501mm ([SD] =
      284). The resulting DSA showed that areas most frequently stimulated were located
      squarely in the middle of the posterior GP, with a common target volume measuring
      153mm(3) . INTERPRETATION: Our results provide a map of the region of influence
      of therapeutic DBS for dystonia and represent a potential target to refine
      current methods of surgical planning and stimulation parameters selection. Based
      on their role in alleviating symptoms, these regions may also provide anatomical
      and physiological information relevant to disease models of dystonia. Further
      experimental and clinical studies will be needed to validate their importance.

PMID- 24852851
TI  - Allergy to formaldehyde: basophil histamine-release test is useful for diagnosis.
AB  - We describe a case of formaldehyde-induced urticaria with a positive test result
      for serum IgE antibody against this substance. Formaldehyde's slow protein
      binding property may explain why basophil histamine-release tests using fresh
      formaldehyde solutions are not diagnostic, whereas the tests are useful if
      formaldehyde that had been stored with albumin is used.

PMID- 24852852
TI  - An analysis of von Economo neurons in the cerebral cortex of cetaceans,
      artiodactyls, and perissodactyls.
AB  - Von Economo neurons (VENs) are specialized projection neurons with a
      characteristic spindle-shaped soma and thick basal and apical dendrites. VENs
      have been described in restricted cortical regions, with their most frequent
      appearance in layers III and V of the anterior cingulate cortex, anterior insula,
      and frontopolar cortex of humans, great apes, macaque monkeys, elephants, and
      some cetaceans. Recently, a ubiquitous distribution of VENs was reported in
      various cortical areas in the pygmy hippopotamus, one of the closest living
      relatives of cetaceans. That finding suggested that VENs might not be unique to
      only a few species that possess enlarged brains. In the present analysis, we
      assessed the phylogenetic distribution of VENs within species representative of
      the superordinal clade that includes cetartiodactyls and perissodactyls, as well
      as afrotherians. In addition, the distribution of fork cells that are often found
      in close proximity to VENs was also assessed. Nissl-stained sections from the
      frontal pole, anterior cingulate cortex, anterior insula, and occipital pole of
      bowhead whale, cow, sheep, deer, horse, pig, rock hyrax, and human were examined
      using stereologic methods to quantify VENs and fork cells within layer V of all
      four cortical regions. VENs and fork cells were found in each of the species
      examined here with species-specific differences in distributions and densities.
      The present results demonstrated that VENs and fork cells were not restricted to
      highly encephalized or socially complex species, and their repeated emergence
      among distantly related species seems to represent convergent evolution of
      specialized pyramidal neurons. The widespread phylogenetic presence of VENs and
      fork cells indicates that these neuron morphologies readily emerged in response
      to selective forces,whose variety and nature are yet to be identified. 

PMID- 24852853
TI  - Circulating free DNA in a screening program for early colorectal cancer
      detection.
AB  - AIMS AND BACKGROUND: The quantification and molecular characterization of
      circulating free DNA (cfDNA) have attracted much interest as new and promising,
      noninvasive means of detecting and monitoring the presence of surgical resectable
      colorectal cancer (CRC). Instead, the role of cfDNA in the early detection of
      malignant and premalignant colorectal lesions is still unclear. The aim of this
      study was to evaluate the predictive power of the quantification and KRAS status
      of cfDNA in detecting early colorectal lesions in plasma from healthy high-risk
      subjects. METHODS: The study population consisted of 170 consecutive healthy high
      risk subjects aged >50 years who participated in the screening program promoted
      by the Local Health Service (ASL-Milano) for early CRC detection and who
      underwent endoscopic examination after being found positive at fecal occult blood
      test (FOBT). Thirty-four participants had malignant lesions consisting of 12
      adenocarcinomas (at an early stage in half of the cases) and 22 instances of high
      grade intraepithelial neoplasia (HGIN) in adenomas; 73 participants had
      premalignant lesions (adenomas and hyperplasia), and 63 participants had no
      lesions. Plasma cfDNA was quantified by quantitative real-time PCR and analyzed
      for KRAS mutations by a mutant-enriched PCR. KRAS status was assessed also in
      matched adenocarcinoma and HGIN tissues. The distribution of cfDNA concentrations
      among FOBT-positive subjects with diagnosed lesion (cases) was compared with that
      of FOBT-positive subjects without lesions (controls) and its predictive
      capability (AUC) was assessed. RESULTS: The predictive capability of cfDNA levels
      was satisfactory in predicting adenocarcinomas (AUC 0.709; 95% CI, 0.508-0.909)
      but not HGIN and premalignant lesions. The rate of KRAS mutations in plasma was
      low (5/170 = 3%) compared with the rate observed in the matched adenocarcinoma
      and HGIN tissues (45%). CONCLUSIONS: The use of cfDNA quantification to predict
      adenocarcinoma at an early stage in high-risk (aged >50 years and FOBT positive)
      subjects seems to be promising but needs more sensitive methods to improve cfDNA
      detection.

PMID- 24852854
TI  - KRAS mutations and M2PK upregulation in stool samples from individuals with
      positive fecal occult blood tests screened for colorectal cancer.
AB  - BACKGROUND: Screening for colorectal cancer (CRC) requires non-invasive methods
      of high diagnostic sensitivity and specificity. We evaluated the measurement of
      genetic and protein biomarkers of CRC in stool samples with the aim of testing
      their clinical utility in a CRC screening program. PATIENTS AND METHODS:
      Individuals aged 53-75 years who were at risk of CRC and immunochemical fecal
      occult blood test (iFOBT) positive were invited to submit stool samples for
      molecular testing prior to colonoscopy. KRAS codon 12 Gly->Asp, Gly, Val, and
      codon 13 Gly->Cys gene mutations were tested using an in-house real-time ARMS PCR
      method. M2PK levels in stool samples were measured utilizing a commercial ELISA
      kit. RESULTS: At colonoscopy, 7.6% of patients were found to have CRC, 50% had
      adenomas, 10.6% had hyperplastic polyps, 20.2% had diverticulosis and
      hemorrhoids, and 11.6% had normal mucosa. The best sensitivity for CRC (50%) was
      found in those cases where M2PK and KRAS abnormalities coexisted. M2PK showed a
      detection rate of 40.3% for adenomas but the combination of M2PK and KRAS
      abnormalities was found in only 5.7% of adenomas (P <0.01). iFOBT was false
      positive in 31.8% of cases in which colonoscopy excluded neoplastic lesions,
      while the coexistence of molecular and enzymatic abnormalities was more specific
      with false positive rates between 8.3% and 9.0% (P <0.05). CONCLUSION: Our
      molecular screening approach demonstrates that detection of cancer-associated
      biomarkers measured in iFOBT-positive stool samples could help separate true from
      false positives in a FOBT-based screening process. M2PK showed particular promise
      for the detection of CRC and adenomas.

PMID- 24852848
TI  - The Brassica oleracea genome reveals the asymmetrical evolution of polyploid
      genomes.
AB  - Polyploidization has provided much genetic variation for plant adaptive
      evolution, but the mechanisms by which the molecular evolution of polyploid
      genomes establishes genetic architecture underlying species differentiation are
      unclear. Brassica is an ideal model to increase knowledge of polyploid evolution.
      Here we describe a draft genome sequence of Brassica oleracea, comparing it with
      that of its sister species B. rapa to reveal numerous chromosome rearrangements
      and asymmetrical gene loss in duplicated genomic blocks, asymmetrical
      amplification of transposable elements, differential gene co-retention for
      specific pathways and variation in gene expression, including alternative
      splicing, among a large number of paralogous and orthologous genes. Genes related
      to the production of anticancer phytochemicals and morphological variations
      illustrate consequences of genome duplication and gene divergence, imparting
      biochemical and morphological variation to B. oleracea. This study provides
      insights into Brassica genome evolution and will underpin research into the many
      important crops in this genus. 

PMID- 24852855
TI  - Sequential dose-dense 5-fluorouracil, epirubicin and cyclophosphamide followed by
      docetaxel in patients with early breast cancer with four or more positive lymph
      nodes.
AB  - AIM: The aim of present study was to investigate the feasibility of a densified
      sequence of FEC75 (5-fluorouracil 600 mg/m2, epirubicin 75 mg/m2,
      cyclophosphamide 600 mg/m2) and docetaxel 100 mg/m2 (D100) in patients with
      primary operable high-risk breast cancer. METHODS: Fifty-one consecutive patients
      with resectable breast cancer and 4 or more positive axillary lymph nodes were
      enrolled. After a common regimen of 4 cycles of FEC75 given every 14 days,
      patients received 4 cycles of D100 every 14 days. Prophylactic granulocyte colony
      stimulating factor was administered subcutaneously at 5 mg/kg daily from days 5
      to 10 to each patient. RESULTS: The primary endpoint was the proportion of
      subjects receiving at least 85% of the relative dose intensity (rDI) both in the
      FEC and docetaxel parts of the regimen. In view of the high percentage of grade 3
      4 skin toxicity (32%) observed in the first 25 patients (Group A) during D100
      treatment, it was decided to continue the study using a docetaxel dose reduced by
      15% (85 mg/m2; D85). This second group of 26 patients was defined as Group B. Of
      the total 51 patients, 38 (75%) received docetaxel rDI >=85%, 23/26 patients
      (88.5%) and 15/25 patients (60.0%) in Group B and Group A, respectively. The
      observed grade 3-4 hematological and nonhematological toxicities were in line
      with data from the literature. The only significant difference was the higher
      percentage of grade 3-4 skin toxicity experienced with D100. CONCLUSION: This
      study failed to demonstrate the feasibility of a dose-dense FEC-D regimen with
      docetaxel 100 mg/m2. Docetaxel 85 mg/m2 seems to allow a higher rDI than
      docetaxel 100 mg/m2 but this should be confirmed in a larger cohort of patients.

PMID- 24852856
TI  - Prognostic function of Ki-67 for pathological complete response rate of
      neoadjuvant chemotherapy in triple-negative breast cancer.
AB  - AIMS AND BACKGROUND: Triple-negative breast cancer (TNBC) has fluctuating
      pathological complete response (pCR) rates to neoadjuvant chemotherapy (NAC)
      according to published reports. Biomarkers predicting pCR rates of NAC would
      improve TNBC patients' outcomes. We conducted a meta-analysis to estimate the
      prognostic function of Ki-67 in relation to pCR rates of NAC in TNBC. METHODS AND
      STUDY DESIGN: Relevant publications in the literature from January 2006 to March
      2013 were selected by searching PubMed, SpringerLink, Web of Science, Scopus and
      the Cochrane Library. The quality of prognostic studies was evaluated according
      to the standard reported by Hayden et al. Relative risk (RR) and 95% confidence
      interval (CI) were used to estimate the prognostic function of Ki-67 for pCR
      rates in TNBC. The fail-safe number was used to detect possible publication bias.
      Review Manager and MIX software was used to merge extracted data. RESULTS: The
      pCR rate of TNBC with high Ki-67 expression was 3.36 times that of low Ki-67
      expression TNBC. The merged RR was 3.36 (95% CI: 1.61-7.02) and the fail-safe
      number was 34. No obvious publication bias but heterogeneity of the case series
      was detected. CONCLUSIONS: Ki-67 was a predictor of pCR rates to NAC in TNBC.

PMID- 24852857
TI  - Do high-risk features support the use of adjuvant chemotherapy in stage II colon
      cancer? A Turkish Oncology Group study.
AB  - BACKGROUND: A high-risk group of patients with stage II colon cancer has been
      identified by the results of studies in Western populations. The aim of this
      study was to investigate the prognostic factors of adjuvant chemotherapy in
      Turkish patients with stage II colon cancer. METHODS: A total of 554 stage II
      colon cancer patients were retrospectively enrolled in the study. Three hundred
      fifty-three patients had received adjuvant chemotherapy (5-FU-LV, FOLFOX or FLOX)
      and 201 had received no adjuvant chemotherapy. T4 tumor stage, lymphovascular
      invasion, perineural invasion, bowel obstruction and/or perforation, <12
      harvested lymph nodes, and poor differentiation were defined as high-risk
      factors. RESULTS: The median age of the patients was 62 years (range 26-88). The
      median disease-free survival (DFS) was 58.1 months (95% CI, 47.6 months to 68.5
      months) in the non-treatment group and has not been reached in the treatment
      group (P <0.01). In univariate analysis, patient age >60 years and T4 tumor stage
      were statistically significant factors that affected DFS as poor prognostic
      factors. Adjuvant chemotherapy reduced the risk of recurrence with statistical
      significance (P <0.01). In multivariate analysis, patient age >60 years and T4
      tumor stage were independent risk factors affecting DFS. In addition, adjuvant
      chemotherapy was an independent favorable prognostic factor for DFS (P <0.01).
      CONCLUSIONS: Clinical and pathological risk factors in patients with stage II
      colon cancer may be different in the Turkish population compared to other
      populations. Further prospective studies in colon cancer are needed to understand
      the differences in biology and risk factors between races.

PMID- 24852858
TI  - Pilot study of intense neoadjuvant chemoradiotherapy for locally advanced rectal
      cancer: retrospective review of a phase II study.
AB  - AIMS AND BACKGROUND: Locally advanced rectal adenocarcinoma is typically treated
      with neoadjuvant chemoradiotherapy and surgery. We assessed the effect of an
      additional cycle of capecitabine/oxaliplatin chemotherapy before surgery in 57
      patients with T3/4, N+/- or T1/2, N+ rectal cancer. MATERIALS AND STUDY DESIGN:
      Radiotherapy (total dose, 50.4 Gy) was combined with three cycles of chemotherapy
      (two cycles concomitant with radiotherapy), and each cycle consisted of
      oxaliplatin (130 mg/m2 on day 1) and capecitabine (825 mg/m2, twice per day from
      day 1 to day 14) for 21 days. In addition to assessing the safety of this
      treatment, the primary endpoint was pathological complete response (pCR). The
      secondary endpoint was the change in primary tumor and node stage from pre
      treatment to post-surgery. RESULTS: Eleven patients (19%) experienced complete
      tumor regression and 23 patients (40%) experienced tumor regression grade 3.
      Tumor down-staging occurred in 31 patients (54.4%) and down-staging of nodes
      occurred in 25 patients (43.9%). There was a significant difference in tumor
      stage between pre-treatment and post-surgery (P <0.001). Patients with less
      advanced N stages had significantly better recurrence-free survival but similar
      metastasis-free survival and overall survival. Tumor regression grade was not
      associated with overall survival, recurrence-free survival or metastasis-free
      survival. The most common adverse events were pulmonary infection (n = 6, 10.5%)
      and intestinal obstruction (n = 6, 10.5%): CONCLUSIONS. An additional cycle of
      chemotherapy given after chemoradiotherapy and before surgery provided good
      efficacy and had a satisfactory safety profile in patients with locally advanced
      rectal cancer.

PMID- 24852859
TI  - Tumor volume reduction assessed by planning computed tomography in patients with
      rectal cancer during preoperative chemoradiation: impact of residual tumor volume
      on the prediction of pathologic tumor regression.
AB  - AIMS AND BACKGROUND: To determine whether the residual tumor volume measured
      using the Eclipse treatment planning system correlates with pathologic tumor
      regression grade after preoperative chemoradiotherpy for rectal cancer. MATERIALS
      AND METHODS: The study included 30 patients with rectal cancer who had undergone
      preoperative chemoradiotherpy followed by surgery from June 2008 to April 2011 at
      the Korea University Guro Hospital. The tumor volume was measured using the
      Eclipse treatment planning system in the initial simulation computed tomography
      and boost planning computed tomography. The correlation between the residual
      tumor volume in boost planning computed tomography and the pathologic tumor
      regression grade was analyzed. Tumor regression grade defined in the American
      Joint Committee on Cancer 7th edition was used. RESULTS: The mean and median
      residual tumor volume was 57.34% +/- 20.37% and 52.35% (range, 18.42%-95.79%),
      respectively. After surgery, pathologic complete response (tumor regression grade
      0) occurred in 4 patients (13.33%), moderate response (tumor regression grade 1)
      in 18 patients (60%), minimal response (tumor regression grade 2) in 4 patients
      (13.33%), and poor response (tumor regression grade 3) in 4 patients (13.33%).
      When residual tumor volume was categorized into two groups (<50% and >=50%),
      complete or moderate regression (tumor regression grade 0 or 1) was significantly
      greater for patients with a residual tumor volume <50% ( P <0.05). The mean
      residual tumor volume of tumor regression grade 0 or 1 was 49.07% +/- 18.39% and
      that of tumor regression grade 2 or 3 was 76.31% +/- 16.94% (P <0.05).
      CONCLUSIONS: Residual tumor volume measured using routine boost planning computed
      tomography during preoperative chemoradiotherpy correlated significantly with
      pathologic tumor regression grade after surgery.

PMID- 24852860
TI  - Mono-institutional Italian experience with a double-lumen balloon-brachytherapy
      device for early breast cancer: results at a 5-year minimum follow-up.
AB  - AIMS AND BACKGROUND: To report the 5-year minimum follow-up in low-risk breast
      cancer patients treated with a double-lumen balloon-brachytherapy device in one
      mono-institutional Italian experience. Local control data and cosmetic outcomes
      were collected and analyzed. METHODS: Between October 2004 and December 2007, we
      treated 30 early stage breast cancer patients who underwent conservative surgery
      followed by adjuvant accelerated partial breast irradiation with a double-lumen
      balloon-brachytherapy system. Eligibility criteria for the protocol were based on
      the indications of the American Brachytherapy Society and the American Society of
      Breast Surgeons. The device was placed inside the lumpectomy cavity during
      surgery by open technique in all the patients. Computed tomography images and
      standard X-ray were used for treatment planning. The total irradiation dose was
      34 Gy in 10 fractions of 3.4 Gy (twice daily) over 5 days to the lumpectomy
      cavity. RESULTS: Median follow-up was 80.5 months (range, 60-98). No patient
      developed local recurrence or distant metastasis. At the end of treatment, there
      was evidence of a symptomatic seroma in 83% of the total patients, with a yearly
      decreasing trend. However, the incidence of mild and moderate fibrosis
      progressively increased. Seventy-seven percent of the patients were satisfied
      with their cosmetic results. CONCLUSIONS: Our findings reinforce the hypothesis
      that an accelerated double-lumen balloon-breast brachytherapy catheter in
      selected low-risk patients is safe, and a favorable cosmetic outcome can be
      achieved.

PMID- 24852861
TI  - Reproducible deep-inspiration breath-hold irradiation with forward intensity
      modulated radiotherapy for left-sided breast cancer significantly reduces cardiac
      radiation exposure compared to inverse intensity-modulated radiotherapy.
AB  - AIMS AND BACKGROUND: To investigate the objective utility of our clinical routine
      of reproducible deep-inspiration breath-hold irradiation for left-sided breast
      cancer patients on reducing cardiac exposure. METHODS AND STUDY DESIGN: Free
      breathing and reproducible deep-inspiration breath-hold scans were evaluated for
      our 10 consecutive left-sided breast cancer patients treated with reproducible
      deep-inspiration breath-hold. The study was based on the adjuvant dose of 50 Gy
      in 25 fractions of 2 Gy/fraction. Both inverse and forward intensity-modulated
      radiotherapy plans were generated for each computed tomography dataset. RESULTS:
      Reproducible deep-inspiration breath-hold plans with forward intensity-modulated
      radiotherapy significantly spared the heart and left anterior descending artery
      compared to generated free-breathing plans based on mean doses - free-breathing
      vs reproducible deep-inspiration breath-hold, left ventricle (296.1 vs 94.5 cGy,
      P = 0.005), right ventricle (158.3 vs 59.2 cGy, P = 0.005), left anterior
      descending artery (171.1 vs 78.1 cGy, P = 0.005), and whole heart (173.9 vs 66
      cGy, P = 0.005), heart V20 (2.2% vs 0%, P = 0.007) and heart V10 (4.2% vs 0.3%, P
      = 0.007) - whereas they revealed no additional burden on the ipsilateral lung.
      Reproducible deep-inspiration breath-hold and free-breathing plans with inverse
      intensity-modulated radiotherapy provided similar organ at risk sparing by
      reducing the mean doses to the left ventricle, left anterior descending artery,
      heart, V10-V20 of the heart and right ventricle. However, forward intensity
      modulated radiotherapy showed significant reduction in doses to the left
      ventricle, left anterior descending artery, heart, right ventricle, and
      contralateral breast (mean dose, 248.9 to 12.3 cGy, P = 0.005). The mean doses
      for free-breathing vs reproducible deep-inspiration breath-hold of the proximal
      left anterior descending artery were 1.78 vs 1.08 Gy and of the distal left
      anterior descending artery were 8.11 vs 3.89 Gy, whereas mean distances to the 50
      Gy isodose line of the proximal left anterior descending artery were 6.6 vs 3.3
      cm and of the distal left anterior descending artery were 7.4 vs 4.1 cm, with
      forward intensity-modulated radiotherapy. Overall reduction in mean doses to
      proximal and distal left anterior descending artery with deep-inspiration breath
      hold irradiation was 39% (P = 0.02) and 52% (P = 0.002), respectively.
      CONCLUSIONS: We found a significant reduction of radiation exposure to the
      contralateral breast, left and right ventricles, as well as of proximal and
      especially distal left anterior descending artery with the deep-inspiration
      breath-hold technique with forward intensity-modulated radiotherapy planning.

PMID- 24852862
TI  - Management of pulmonary oligometastases by stereotactic body radiotherapy.
AB  - AIMS AND BACKGROUND: The aim of the study was to evaluate the feasibility,
      toxicity and effectiveness of active breathing control-guided stereotactic body
      radiotherapy in the management of pulmonary oligometastases. METHODS AND STUDY
      DESIGN: Between June 2010 and June 2012, 20 patients (13 males, 7 females) with
      31 pulmonary metastases referred to the Department of Radiation Oncology, Gulhane
      Military Medical Academy were treated using active breathing control-guided
      stereotactic body radiotherapy. Response Evaluation Criteria in Solid Tumors and
      Common Terminology Criteria for Adverse Events were used in the assessment of
      treatment response and toxicity, respectively. RESULTS: Assessment of treatment
      response revealed complete response, partial response, stable disease, and
      progressive disease in 30%, 25%, 30%, and 15% of the patients, respectively. At a
      median follow-up of 14 months, local control was 85% and overall survival was
      70%, with negligible treatment-related toxicity. CONCLUSIONS: Stereotactic body
      radiotherapy is safe and effective in the management of pulmonary
      oligometastases. It offers favorable treatment outcomes as a viable non-invasive
      therapeutic modality.

PMID- 24852863
TI  - Evaluation of linear accelerator-based stereotactic radiosurgery in the
      management of glomus jugulare tumors.
AB  - AIMS AND BACKGROUND: Although mostly benign and slow-growing, glomus jugulare
      tumors have a high propensity for local invasion of adjacent vascular structures,
      lower cranial nerves and the inner ear, which may result in substantial morbidity
      and even mortality. Treatment strategies for glomus jugulare tumors include
      surgery, preoperative embolization followed by surgical resection, conventionally
      fractionated external beam radiotherapy, radiosurgery in the form of stereotactic
      radiosurgery or fractionated stereotactic radiation therapy, and combinations of
      these modalities. In the present study, we evaluate the use of linear accelerator
      (LINAC)-based stereotactic radiosurgery in the management of glomus jugulare
      tumors and report our 15-year single center experience. METHODS AND STUDY DESIGN:
      Between May 1998 and May 2013, 21 patients (15 females, 6 males) with glomus
      jugulare tumors were treated using LINAC-based stereotactic radiosurgery at the
      Department of Radiation Oncology, Gulhane Military Medical Academy. The
      indication for stereotactic radiosurgery was the presence of residual or
      recurrent tumor after surgery for 5 patients, whereas 16 patients having growing
      tumors with symptoms received stereotactic radiosurgery as the primary treatment.
      RESULTS: Median follow-up was 49 months (range, 3-98). Median age was 55 years
      (range, 24-77). Of the 21 lesions treated, 13 (61.9%) were left-sided and 8
      (38.1%) were right-sided. Median dose was 15 Gy (range, 10-20) prescribed to the
      85%-100% isodose line encompassing the target volume. Local control defined as
      either tumor shrinkage or the absence of tumor growth on periodical follow-up
      neuroimaging was 100%. CONCLUSIONS: LINAC-based stereotactic radiosurgery offers
      a safe and efficacious management strategy for glomus jugulare tumors by
      providing excellent tumor growth control with few complications.

PMID- 24852864
TI  - Radiotherapy in patients with vestibular schwannoma and neurofibromatosis type 2:
      clinical results and review of the literature.
AB  - AIMS AND BACKGROUND: To evaluate the long-term outcome of patients with
      vestibular schwannoma (VS) and neurofibromatosis type 2 (NF2) treated with
      fractionated stereotactic radiotherapy (FSRT) or stereotactic radiosurgery (SRS).
      PATIENTS AND METHODS: Sixteen VS in 14 patients with NF2 were treated with FSRT
      (n = 14) and SRS (n = 2). Patients with tumor progression and/or progression of
      clinical symptoms were selected for treatment. For patients treated with FSRT a
      median total dose of 57.6 Gy was prescribed with a median fractionation of 5 *
      1.8 Gy per week. For patients who underwent SRS a median single dose of 17 Gy was
      prescribed to the 80% isodose. RESULTS: FSRT and SRS were well tolerated. Local
      control rate was 94% for a median follow-up time of 131 months; 2- and 5-year
      progression-free survival were 100%. The probability of maintaining the
      pretreatment hearing level was 44%. Useful hearing preservation was 33%. Cranial
      nerve toxicity was moderate. Trigeminal nerve function worsened in 2 patients
      (12%) and facial nerve function in 3 patients (19%). One patient developed a new
      tinnitus. CONCLUSION: FSRT and SRS are both safe and effective noninvasive and
      minimally invasive treatment options for patients with VS in the setting of NF2.
      The long-term local control rates are excellent. Functional hearing preservation
      is worse in patients with VS and NF2 than in patients with sporadic VS.

PMID- 24852866
TI  - Usefulness of combined PET/CT to assess regional lymph node involvement in
      gastric cancer.
AB  - AIMS AND BACKGROUND: The aim of this study was to evaluate the value of positron
      emission tomography/computed tomography (PET/CT) for preoperative staging of
      gastric cancer and to compare the diagnostic performance of PET/CT with that of
      contrast-enhanced computed tomography (CECT). METHODS: We retrospectively
      reviewed 74 gastric cancer patients who underwent preoperative PET/CT and CECT,
      and subsequent curative surgical resection between April 2007 and July 2011.
      Preoperative PET/CT and CECT images for primary tumors of the stomach and lymph
      node metastases were reviewed retrospectively. The final diagnoses of primary
      tumors and LN metastases were based on histopathological specimens in all
      patients. RESULTS: Advanced gastric cancer was present in 65% of patients (n =
      48), and the remaining patients had early gastric cancer (n = 26). Sixteen
      patients (22%) showed signet-ring-cell histology. For the detection of the
      primary tumor, the sensitivity of PET/CT was significantly higher than that of
      CECT (67% vs 55%, respectively; P = 0.049). For the evaluation of regional lymph
      node metastasis, the sensitivity, specificity, and accuracy of PET/CT and CECT
      were 34% and 51% (P = 0.065), 88% and 79% (P = 0.687), and 58% and 64% (P =
      0.332), respectively. Neither PET/CT nor CECT detected regional lymph node
      metastases in early gastric cancer patients. Signet-ring-cell histology showed
      trends of non-FDG-avid lymph node metastases (odds ratio = 0.15, 95% confidence
      interval 0.17-1.37, P = 0.093). CONCLUSIONS: The accuracy of PET/CT is low and it
      is not a useful tool in the staging of gastric cancer overall in early gastric
      cancer and in signet-ring-cell carcinoma. Furthermore, the sensitivity of PET/CT
      could be inferior to that of CECT in the diagnosis of regional lymph node
      metastasis.

PMID- 24852865
TI  - Incidence and dose-volume analysis of acute bladder toxicity following pelvic
      radiotherapy.
AB  - AIMS AND BACKGROUND: The authors performed this prospective study to evaluate the
      incidence of acute bladder toxicity following pelvic radiation therapy and to
      determine any dosimetric predictors for the toxicity. METHODS AND STUDY DESIGN:
      Acute bladder toxicity was evaluated weekly by physicians using the Common
      Terminology Criteria for Adverse Events (CTCAE version 4.0). At the same time,
      the International Prostate Symptom Score (IPSS) and Overactive Bladder Symptom
      Score (OABSS) were also assessed by each patient during radiation therapy. We
      contoured the bladder wall, solid bladder and trigone on the planning computed
      tomography and analyzed dose-volume histograms to determine which of these could
      be the most suitable dosimetric predictor. RESULTS: Of 92 eligible patients, 27
      (29%) demonstrated CTCAE grade 2 acute bladder toxicity, with nocturia as the
      most frequently observed symptom. IPSS demonstrated better agreement with CTCAE
      than OABSS. In receiver-operating characteristic curve analysis, the largest area
      under the curve was observed for V20 of both the bladder wall and the bladder.
      CONCLUSIONS: Acute bladder toxicity during pelvic radiation therapy is not a
      trivial complication and should be actively investigated. Dose-volume
      relationships demonstrate that both bladder wall V20 and bladder solid V20 are
      useful surrogates for identifying patients at high risk of toxicity. The roles of
      IPSS and OABSS need to be validated in a larger study.

PMID- 24852867
TI  - Comparing five diagnostic criteria for multiple myeloma: a retrospective study of
      227 cases.
AB  - AIMS AND BACKGROUND: Several diagnostic criteria for multiple myeloma are used in
      clinical practice, and it can be difficult to reach a diagnosis when a patient's
      clinical presentation is consistent with one criterion but not with another.
      However, no study to date has compared the superiority of the different
      diagnostic criteria. The aim of this research is to compare the efficacy of five
      diagnostic criteria for multiple myeloma and to find the reasons for misdiagnosis
      of atypical multiple myeloma cases. METHODS AND STUDY DESIGN: A total of 227
      multiple myeloma cases were retrospectively studied. The clinical data (including
      plasma cell morphology, flow cytometry, immunofixation electrophoresis, imaging
      information and clinical manifestations) were scrutinized and the reasons
      underlying the misdiagnoses analyzed. RESULTS: The Traditional Domestic criteria
      had the highest misdiagnosis rate due to the high fixed bone marrow plasma cell
      percentage and serum M-protein thresholds. The WHO criteria and the International
      Myeloma Working Group 2009 criteria exhibited relatively low misdiagnosis rates
      due to their lower bone marrow plasma cell percentage thresholds, flexible
      criteria and detailed end-organ damage descriptions. The 2003 International
      Myeloma Working Group criteria and the 2011 Chinese Myeloma Working Group
      criteria exhibited perfect performance, as each focused on monoclonal plasma cell
      proliferation and not on fixed bone marrow plasma cell percentage and serum M
      protein thresholds. CONCLUSIONS: The 2003 International Myeloma Working Group
      criteria and the 2011 Chinese Myeloma Working Group criteria have advantages in
      diagnosing early or atypical multiple myeloma cases. To avoid misdiagnosing some
      atypical cases of multiple myeloma, attention should be paid to evidence of
      monoclonal plasma cell proliferation, and flow cytometry may be a useful tool for
      discovering monoclonal plasma cell proliferation. Advanced imaging techniques
      should be used to confirm any suspected or atypical findings on metastatic bone
      survey.

PMID- 24852868
TI  - Serum ALDH1A1 is a tumor marker for the diagnosis of non-small cell lung cancer.
AB  - BACKGROUND: ALDH1A1 (aldehyde dehydrogenase 1 family, member A1) is highly
      expressed in non-small-cell lung cancer (NSCLC). We assessed the potential
      clinical value of serum ALDH1A1 in the diagnosis and prognosis of non-small-cell
      lung cancer. METHOD: Between 2010 and 2011, serum samples from 100 non-small-cell
      lung cancer patients before tumor resection, 60 patients with benign lung
      disease, and 60 healthy volunteers were collected and analyzed retrospectively
      for ALDH1A1, using sandwich ELISA. We further evaluated the serum and tumor
      ALDH1A1 levels of non-small-cell lung cancer patients before and after surgery.
      We compared the diagnostic and prognostic values of serum ALDH1A1 with that of
      carcinoembryonic antigen. RESULTS: Elevated serum ALDH1A1 levels were observed in
      55 of the 100 (55%) non-small-cell lung cancer patients. The ALDH1A1 levels were
      much higher in patients with advanced stages than in those with early stage
      tumors. Of the 30 non-small-cell lung cancer patients who underwent surgery, 19
      had elevated serum ALDH1A1 levels before surgery, but the serum ALDH1A1 level was
      undetectable by postoperative day 7. Analysis of receiver operating
      characteristic curves showed that ALDH1A1 might be better than carcinoembryonic
      antigen in distinguishing non-small-cell lung cancer from benign disease or the
      healthy control. Combined application of ALDH1A1 and carcinoembryonic antigen
      significantly increased the sensitivity of carcinoembryonic antigen alone, with
      an accuracy of 83%. CONCLUSIONS: Our results showed that serum levels of ALDH1A1
      were correlated with carcinogenesis and progression of non-small-cell lung
      cancer. Detection of serum ALDH1A1 can be helpful in the diagnosis and prognosis
      of non-small-cell lung cancer. The diagnosis rate of non-small-cell lung cancer
      could be significantly improved when carcinoembryonic antigen is combined with
      ALDH1A1.

PMID- 24852869
TI  - Outcome and patterns of care in advanced biliary tract carcinoma (ABC):
      experience from two tertiary institutions in the United Kingdom.
AB  - AIMS AND BACKGROUND: The ABC-02 trial has defined the standard therapy for
      patients with advanced biliary tract cancer (ABC); however, outcome in an
      unselected patient population in the UK has not been described. We aimed to
      investigate the outcome of a series of patients with ABC from two large UK cancer
      networks. METHODS AND STUDY DESIGN: We retrospectively reviewed all cases of ABC
      presenting to two UK cancer networks over a nine-year period. Overall survival
      (OS) and factors influencing OS were assessed. RESULTS: Four hundred and two
      patients were available for analysis. The median OS was 6.2 months. On univariate
      analysis, age >=70 years (P = 0.047), advanced disease stage (P <0.001), gall
      bladder primary (P = 0.033), poor performance status (P <0.001) and lack of
      chemotherapy (P <0.001) were associated with worse outcome. Survival was superior
      in the 36.4% of patients who received palliative chemotherapy (12.5 vs 4.3
      months; P <0.001). On multivariate analysis of patients who had chemotherapy,
      those who did not receive fluoropyrimidine-based regimens (HR = 5.12; P = 0.022)
      or gemcitabine-based regimens (HR = 5.01; P = 0.021) had a higher mortality,
      whereas the effect of platinum-containing regimens was of borderline significance
      (HR = 2.23; P = 0.086). Sites, age, and multi-agent regimens were not
      significant. CONCLUSIONS: This is one of the largest retrospective studies
      reporting outcome of palliative chemotherapy for ABC. It confirms the benefit of
      palliative chemotherapy in an unselected group of patients. Fluoropyrimidine
      based regimens appear to be as effective as gemcitabine-based treatments.

PMID- 24852871
TI  - Sexual satisfaction assessment in 194 nonmetastatic cancer patients on treatment
      or in follow-up.
AB  - AIMS AND BACKGROUND: Sexuality is an important aspect of quality of life, but
      health care professionals still avoid discussing sexual issues with cancer
      patients. METHODS AND STUDY DESIGN: We present a secondary analysis of sexuality
      issues according to the results of a survey on 266 patients with early-stage
      cancer. The aim of the survey was to ascertain the feasibility and clinical
      usefulness of questionnaires (Patient Dignity Inventory, PDI; Hospital Anxiety
      and Depression Scale, HADS; Edmonton Symptom Assesssment Scale, ESAS; FACIT
      spiritual well-being scale, FACIT-SP; System of Belief Inventory, SBI-15R)
      investigating aspects such as dignity, hope and research of meaning in life. The
      present study is an ancillary analysis of the full sample, and we have focused on
      the results of FACIT-SP about the correlation between sexual satisfaction and
      clinical characteristics in 108 patients having solid tumors and 86 having
      hematological malignancies with no metastases who were on active cancer treatment
      or in follow-up in four different cancer treatment settings during the first half
      of 2011. RESULTS: The median age of the 194 patients was 65 years, 112 were
      women, 155 were undergoing treatment and 39 were in follow-up. Eighty-three
      patients were above the cutoff score for HADS. Among the 171 believers, 80 were
      churchgoers and 91 were nonchurchgoers, whereas the nonbelievers among the
      patients were 23. Thirty-five percent of the patients did not respond to the
      sexuality item of the questionnaire. Among the responders (n = 126), 36% reported
      having no sexual satisfaction (score = 0). Sexual dissatisfaction was greater in
      older patients (47% vs 31%, not significant [NS]), women (43% vs 27%, NS),
      patients on treatment (38% vs 25%, NS), patients who requested psychological
      support (53% vs 25%, P = 0.001), patients with high levels of anxiety and
      depression, i.e., HADS scores >10 (44% vs 30%, NS), nonbelievers (61% vs 34%
      among churchgoers, 29% among believers but nonchurchgoers, P = 0.046).
      CONCLUSIONS: One out of 3 patients did not respond to the item on sexuality.
      Among the responders, 1 out of 3 reported having no sexual satisfaction. Half of
      the patients receiving psychological support considered their sexual life not
      satisfying. Clinical interviews and specific questionnaires on sexuality should
      be used to investigate this particular aspect.

PMID- 24852872
TI  - The increasing incidence of remote metastasis: a case report of metastatic
      hepatocellular carcinoma to the rectosigmoid.
AB  - As the fifth most common malignancy worldwide, survival rates of hepatocellular
      carcinoma (HCC) have only slightly improved over the years due to early-stage
      detection. HCC is well known to metastasize to the lung, lymph nodes, and
      musculoskeletal regions; however, only 0.5% to 6% of HCCs metastasize to the
      gastrointestinal tract. In the case described here, a CT scan and subsequent
      colonoscopy of a 51-year-old Asian male with a history of hepatitis B and HCC
      revealed a mass lesion of metastatic HCC 12 cm from the anal verge. Because
      metastatic HCC to the lower gastrointestinal tract has only recently been
      reported, it is speculated that the prolonged survival of patients is also
      increasing the incidence of extrahepatic metastasis, giving the disease greater
      opportunity to spread to more distant regions of the body. This case may be the
      farthest metastasis within the gastrointestinal tract to date.

PMID- 24852870
TI  - Darbepoetin alfa administered once every three weeks for the treatment of anemia
      in elderly patients with non-myeloid tumors receiving chemotherapy.
AB  - AIMS AND BACKGROUND: The present study aims to describe the hematological
      response to darbepoetin alfa (DA) under daily clinical practice conditions in
      anemic elderly patients with non-myeloid tumors receiving chemotherapy. METHODS
      AND STUDY DESIGN: This was a prospective, observational, multicenter study in
      elderly (>=65 years) patients with non-myeloid cancer receiving DA (500 MUg every
      3 weeks) for chemotherapy-induced anemia (hemoglobin [Hb] level <=11.0 g/dL).
      RESULTS: A total of 102 anemic patients with solid tumors and 51 with
      hematological malignancies were included in 28 centers in Spain. Mean age (+/-SD)
      was 73.4 (+/-5.8) years, and mean baseline Hb level was 10.0 (+/-0.8) g/dL. DA
      was administered for a median of 8 weeks. Of the 115 subjects with a post
      baseline Hb value, the percentage of patients who achieved a hematopoietic
      response (Hb increase >=2 g/dL or reaching >=12 g/dL without transfusions in the
      previous 28 days) was 69.7% (95% CI 56.1% to 83.3%). Functional Assessment of
      Cancer Therapy-Fatigue subscale scores increased during the study (median change
      1.0 [Q1 -5.0, Q3 9.0], P = 0.04). One patient (0.7%) experienced a non-serious
      adverse reaction (cutaneous rash). CONCLUSION: The study results suggest that DA
      is an effective and well-tolerated therapy for the treatment of chemotherapy
      induced anemia in elderly patients.

PMID- 24852873
TI  - Minimizing a tricky situation in breast irradiation with helical tomotherapy.
AB  - We report on a patient with breast cancer undergoing adjuvant intensity-modulated
      whole breast and lymph node irradiation with static angle tomotherapy
      (TomoDirect), who experienced a traumatic ipsilateral humeral fracture and was
      able to continue radiotherapy with helical tomotherapy and daily dosimetric
      monitoring by means of the Planned Adaptive module.

PMID- 24852874
TI  - Technical and clinical description of a case of extensive anogenital Paget's
      disease associated with anal cancer treated by tomotherapy.
AB  - In this paper we describe a case of extramammary Paget's disease associated with
      anal cancer, which was successfully treated by intensity-modulated radiotherapy
      using tomotherapy with a simultaneous integrated boost and daily image guidance.
      The main pitfall in this report is the relatively short follow-up (1 year), which
      means that the evaluated data is promising but not conclusive. Considering the
      rarity and wide extension of our patient's Paget's disease in the anogenital
      region, and the lack of literature reports about curative radiotherapy in this
      particular setting, this case report may be considered the first related to
      extensive extramammary Paget's disease treated by tomotherapy.

PMID- 24852875
TI  - A case of lung adenocarcinoma with postoperative recurrence of multiple bone
      metastases that showed a gradual complete response to combined administration of
      erlotinib and zoledronic acid.
AB  - We describe a case of lung adenocarcinoma with multiple postoperative bone
      metastases that showed a gradual but complete response to combined administration
      of erlotinib and zoledronic acid. A 76-year-old man with moderately
      differentiated adenocarcinoma underwent a radical left upper lobectomy and
      mediastinal lymph node dissection. Three and a half years after the operation,
      serum carcinoembryonic antigen (CEA) was elevated and 18F-fluorodeoxyglucose
      positron emission tomography (18FDG-PET) revealed multiple bone metastases.
      Pretreatment evaluation of EGFR mutations in the resected primary adenocarcinoma
      specimen showed an L858R mutation in exon 21. Gefitinib was started as first-line
      treatment. However, evaluation 1 month after administration revealed progressive
      disease. Erlotinib was started as second-line treatment, and evaluation 1 month
      after administration revealed that the disease was stable. Administration of
      zoledronic acid was then begun with continuation of erlotinib. After 2 courses of
      zoledronic acid, the serum CEA level had not changed but the maximum standardized
      uptake values of each region uniformly decreased. Furthermore, the uptake of
      18FDG completely disappeared after 6 courses. Subsequently, the serum CEA level
      continued to decrease and the disappearance of 18FDG uptake was confirmed after
      10 courses (12 months after initiation of erlotinib administration). Our results
      suggest that the combined administration of both drugs is effective against bone
      metastases.We experienced a case of lung adenocarcinoma with postoperative
      recurrence of multiple bone metastases that showed a gradual but complete
      response to combined administration of erlotinib and zoledronic acid. Our results
      suggest that the combined treatment of both drugs is an effective therapy against
      bone metastases.

PMID- 24852876
TI  - Gefitinib leads to complete resolution of postoperative cervical chyloma and
      chylothorax in a lung cancer patient.
AB  - Cervical chyloma is a not uncommon complication after neck surgery, especially
      following diagnostic excision of supraclavicular lymph nodes. Conservative
      treatment remains the standard approach but is inevitably distressful. We
      describe the case of a 60-year-old Asian woman who was diagnosed as having
      adenocarcinoma of the lung with cervical and supraclavicular node involvement.
      She developed persistent cervical chyle leak after excisional biopsy of the
      supraclavicular nodes and proved refractory to all management. Subsequent
      gefitinib therapy led to rapid resolution of chyloma and tumor regression. This
      case provided a unique experience of managing intractable postoperative chyloma
      in a cancer patient.

PMID- 24852877
TI  - Surgical treatment of an isolated omental cervical cancer recurrence: report of a
      case and review of the literature.
AB  - AIMS AND BACKGROUND: Recurrent cervical cancer has traditionally been associated
      with a dismal prognosis. Historically, patients who developed distant metastases
      from cervical cancer were not considered eligible for surgical resection; only
      palliative treatment options are available, generally consisting of chemo- and/or
      radiotherapy. Metastases usually appear in the liver, lung or lymph nodes. The
      abdominal cavity is a quite unusual site of recurrence and the disease usually
      has multiple foci. For this reason, peritoneal involvement by cervical cancer is
      considered a contraindication to local treatment. METHODS AND STUDY DESIGN: We
      report the first case of a 30-year-old woman with isolated intra-abdominal
      cervical cancer recurrence diagnosed with 18F-FDG PET/CT, successfully surgically
      treated. RESULTS: Histopathological analysis confirmed the tumor to be an omental
      relapse of squamous cervical cancer previously treated with anterior pelvic
      exenteration and platinum based chemotherapy. The patient underwent adjuvant
      treatment with 3 cycles of topotecan and has remained free of disease during the
      4 years of follow-up. CONCLUSIONS: In selected cases with isolated recurrences, a
      surgical resection may provide a long term complete remission in recurrent
      cervical cancer patients.

PMID- 24852879
TI  - Case report of a long-surviving man with metastatic renal cell carcinoma treated
      with pazopanib.
AB  - Renal cell carcinoma is the most common type of kidney cancer in adults. It
      accounts for approximately 3% of adult malignancies and 90-95% of neoplasms
      arising from the kidney. At the moment several biological agents are used for the
      treatment of metastatic renal cell carcinoma. We describe the case of a man who
      has been treated with pazopanib (Votrient) for metastatic renal cell carcinoma
      since July 2011. At the time of writing, the patient is still receiving treatment
      (29 months) and is showing a long-lasting response with a favorable safety
      profile. This is an excellent example of chronic neoplastic disease in a patient
      who can be defined as long-surviving.

PMID- 24852878
TI  - Management of a ruptured mucinous mesenteric cyst with hyperthermic
      intraperitoneal chemotherapy.
AB  - Mesenteric cysts are rare intra-abdominal cysts that are generally regarded as
      benign, and the incidence of malignancy is often cited to be 3%. The typical
      recommendation for treatment is complete excision to minimize recurrence.
      Excision can be performed laparoscopically, but this can lead to intra-abdominal
      dissemination of the cyst contents. There has been one case report describing the
      development of pseudomyxoma peritonei following rupture of a mesenteric cyst. We
      describe the treatment and outcome of a patient who underwent cytoreductive
      surgery with hyperthermic intraperitoneal chemotherapy for the treatment of an
      incompletely resected mucinous cystadenocarcinoma originating from the colonic
      mesentery.

PMID- 24852881
TI  - Room temperature plasmonic lasing in a continuous wave operation mode from an
      InGaN/GaN single nanorod with a low threshold.
AB  - It is crucial to fabricate nano photonic devices such as nanolasers in order to
      meet the requirements for the integration of photonic and electronic circuits on
      the nanometre scale. The great difficulty is to break down a bottleneck as a
      result of the diffraction limit of light. Nanolasers on a subwavelength scale
      could potentially be fabricated based on the principle of surface plasmon
      amplification by stimulated emission of radiation (SPASER). However, a number of
      technological challenges will have to be overcome in order to achieve a SPASER
      with a low threshold, allowing for a continuous wave (cw) operation at room
      temperature. We report a nano-SPASER with a record low threshold at room
      temperature, optically pumped by using a cw diode laser. Our nano-SPASER consists
      of a single InGaN/GaN nanorod on a thin SiO2 spacer layer on a silver film. The
      nanorod containing InGaN/GaN multi-quantum-wells is fabricated by means of a cost
      effective post-growth fabrication approach. The geometry of the
      nanorod/dielectric spacer/plasmonic metal composite allows us to have accurate
      control of the surface plasmon coupling, offering an opportunity to determine the
      optimal thickness of the dielectric spacer. This approach will open up a route
      for further fabrication of electrically injected plasmonic lasers. 

PMID- 24852882
TI  - Gastric acid-dependent diseases: a twentieth-century revolution.

PMID- 24852883
TI  - R-spondin2 activates hepatic stellate cells and promotes liver fibrosis.
AB  - BACKGROUND: The development of liver fibrosis is the fundamental stage toward a
      number of mortal complications of liver diseases, including cirrhosis and
      hepatocellular carcinoma. Canonical Wnt pathway is crucial in diverse biological
      processes and mediates the progression and regression of liver fibrosis. As a
      potent Wnt pathway agonist, the role of roof plate-specific spondin-2 (R
      Spondin2) in the hepatic fibrosis has not been well elucidated. AIMS: The purpose
      of this study was to investigate whether R-Spondin2 contributes to hepatic
      stellate cells (HSCs) activation, the key event in liver fibrogenesis. METHODS:
      Human liver tissues, hepatic fibrosis mouse model, and freshly isolated mice HSCs
      were used. Protein expression and transcriptional level were analyzed by Western
      blot assays and real-time PCR, respectively. Exogenous stimulation with
      recombinant R-Spondin2 and knockdown of R-Spondin2 were performed to investigate
      functionality. Nuclear beta-catenin level and T cell-specific transcription
      factors activity were analyzed, and HSC proliferation was tested by MTT assay.
      RESULTS: Overexpression of R-Spondin2 was observed in both human fibrotic liver
      tissues and hepatic fibrosis mouse model. Exogenous stimulation with R-Spondin2
      in the freshly isolated mice HSCs induced a dose-dependent increase in Wnt
      pathway activities, HSC proliferation, and the expression of alpha-smooth muscle
      actin (alpha-SMA) and Collagen I. Additionally, Wnt pathway activities, HSC
      proliferation, and the expressions of alpha-SMA and Collagen I decreased in the R
      Spondin2 knockdown HSCs. CONCLUSIONS: These findings suggest that R-Spondin2 may
      promote HSC activation by enhancing the canonical Wnt pathway.

PMID- 24852884
TI  - Pain provocation and low gallbladder ejection fraction with CCK cholescintigraphy
      are not predictive of chronic acalculous gallbladder disease symptom relief after
      cholecystectomy.
AB  - INTRODUCTION: Chronic acalculous gallbladder disease (CAGD) falls within the
      spectrum of diseases associated with gallbladder dysmotility. Cholecystokinin
      cholescintigraphy (CCK-CS) has been used to evaluate for CAGD, with a gallbladder
      ejection fraction (GBEF) of <35 % being indicative of gallbladder dysfunction.
      The reproduction of biliary colic upon administration of CCK has been cited as
      indicative of CAGD. Our purpose was to determine whether low GBEF or reproduction
      of pain during CCK-CS was predictor of surgical outcomes related to resolution of
      symptoms or as a correlate to gallbladder pathology. METHODS: A retrospective
      review of patients was performed to evaluate adults with a diagnosis of CAGD who
      underwent CCK-CS prior to surgical intervention. CPT and ICD-9 coding queries
      were used to identify the patient population. Patients with cholelithiasis were
      excluded. RESULTS: Sixty-four patients met inclusion criteria. Two patients were
      lost to follow-up and were excluded. During CCK-CS, 41 patients (66 %) reported
      symptoms similar to their presenting complaint. Twenty-one patients reported no
      symptoms with CCK-CS. There was no significant relationship between gallbladder
      pathology and either GBEF or reproduction of symptoms with CCK-CS (p = 0.14).
      About 81 % of patients (n = 50) had relief of symptoms following cholecystectomy.
      Sixty-six percentage of patients (n = 33) with long-term symptom relief after
      cholecystectomy had reproduction of symptoms with CCK-CS. Nineteen percentage of
      all patients (n = 12) had long-term symptom recurrence despite surgery. Eight of
      these patients (66 %) had symptom reproduction with CCK-CS. There was no
      significant correlation with either the GBEF or symptoms reproduction with CCK-CS
      as a predictor of postoperative outcome (p = 0.12). CONCLUSION: Provocation of
      pain by CCK-CS and low GBEF are unreliable predictors of postoperative relief of
      symptoms following cholecystectomy for biliary dyskinesia or chronic acalculous
      gallbladder disease.

PMID- 24852885
TI  - The expression level of TRAF1 in human gastric mucosa is related to virulence
      genotypes of Helicobacter pylori.
AB  - OBJECTIVE: To investigate the expression level of tumor necrosis factor receptor
      associated factor 1 (TRAF1) in gastric mucosa tissue in patients infected with
      Helicobacter pylori (H. pylori) and to analyze the relationship between TRAF1
      expression and H. pylori virulence. METHODS: Gastric tissue samples were
      collected from patients with gastritis, atrophic gastritis, intestinal metaplasia
      with atypical hyperplasia, and gastric cancer. The expression level of TRAF1 in
      each group was analyzed by real-time polymerase chain reaction (PCR) and Western
      blot analysis. Virulence genotypes of H. pylori were determined by PCR. RESULTS:
      Significant differences in TRAF1 mRNA levels were observed between the gastritis
      and gastric cancer groups, and the atrophic gastritis and gastric cancer groups
      (p < 0.05). Moreover, significant differences in TRAF1 protein levels were
      observed between the gastritis and intestinal metaplasia with atypical
      hyperplasia groups, between the gastritis and gastric cancer groups, and between
      the atrophic gastritis and gastric cancer groups (all p < 0.05). The virulence
      genotypes of cytotoxin-associated gene A (cagA), vacAs1, and vacAm1 were more
      frequent in the TRAF1 high-level group than in the TRAF1 low-level group (p <
      0.05). CONCLUSION: Higher TARF1 expression level is associated with infection by
      CagA(+)/vacAs1(+)/m1(+) virulent H. pylori strains and may promote the
      proliferation of gastric mucosal cells and induce gastric cancer.

PMID- 24852886
TI  - Oregonin from the Bark of Alnus japonica restrained ischemia-reperfusion-induced
      mesentery oxidative stress by inhibiting NADPH oxidase activation.
AB  - OBJECTIVE: NADPH oxidase activation results in ROS overproduction that is the
      pathological basis of I/R injury. This study aimed to investigate potential
      effects of ORG on I/R-induced ROS production in rat mesenteric microvasculature
      and underlying mechanisms. METHODS: Mesenteric I/R in Male Wistar rats (200~250
      g) was induced by ligation of the mesenteric artery and vein for 10 minutes
      followed by reperfusion for 60 minutes by releasing of the occlusion. The rats
      were infused intravenously with or without ORG (5 mg/kg per hour) 10 minutes
      before ischemia (pretreatment) or 20 minutes after reperfusion (posttreatment).
      The DHR fluorescence intensity on, the leukocytes adherent to, and mast cell
      degranulation out of mesenteric venules were determined using an intravital
      microscope. NADPH oxidase subunit p47(phox) membrane translocation in intestine
      tissues was detected by Western blotting. RESULTS: Pre- or posttreatment with ORG
      inhibited I/R-induced DHR fluorescence intensity on the venular walls and
      leukocytes adhesion, ORG pretreatment inhibited mast cell degranulation as well.
      Furthermore, the translocation of p47(phox) from cytosol to membrane was
      suppressed markedly by ORG after I/R. CONCLUSIONS: The results suggested that ORG
      restrained I/R-induced ROS production, which might be correlated with its
      inhibitive effect on NADPH activation.

PMID- 24852888
TI  - Progression of alterations in lipid metabolism in kidney transplant recipients
      over 5 years of follow-up.
AB  - BACKGROUND: Alterations in lipid metabolism frequently affect kidney transplant
      recipients and contribute to the onset of metabolic and cardiovascular diseases
      that threaten graft integrity. The purpose of this research study was to
      investigate the pattern of hyperlipidaemia and its progression, as well as to
      study potential risk factors in kidney transplant recipients. METHODS: In this
      study, 119 kidney transplant recipients of both sexes were monitored over a
      period of 5 years in our posttransplant clinic. During this period, all patients
      had pretransplant and posttransplant blood tests to measure levels of the
      following: total cholesterol, low-density lipoproteins (LDL), high-density
      lipoproteins (HDL) and triglycerides. Furthermore, the subjects were also weighed
      and their height measured. Their body mass index was then calculated using the
      weight (kg)/height (m(2) ) formula. RESULTS: In the 5 years following the
      transplant, the patients experienced a significant increase in the levels of
      their biochemical markers as well as in their BMI. Consequently, a greater number
      suffered from dyslipidaemia, diabetes and hypertension. CONCLUSIONS: Kidney
      transplants can often trigger hyperlipidaemia, as reflected in higher levels of
      total cholesterol, low-density lipoproteins and high-density lipoproteins. The
      results of our study also showed that despite statin therapy, the patients had
      higher triglyceride levels, which made them more vulnerable to diabetes,
      hypertension, cardiovascular disease and graft rejection.

PMID- 24852889
TI  - Empathy at a distance: a qualitative study on the impact of publically-displayed
      art on observers.
AB  - While there is some evidence in the literature on the impact of art therapy for
      consumers, there is comparatively little written on how art that has been created
      by consumers impacts on those observing the art. This paper reports on a
      qualitative research study that sought to determine if publically-displayed art
      created by young consumers impacted on stigma reduction and self-help-seeking
      behaviours of the observers. The findings derived from the thematic analysis of
      qualitative interviews suggested that publically-displayed art is a safe medium,
      through which empathy and understanding towards young people with mental illness
      can be enhanced, and that the art generates discussion and self-help behaviours
      for mental illness. These findings highlight how mental health nurses can promote
      social inclusion and reduce stigma through public mental health initiatives that
      are an important inclusion in the scope of mental health nursing practice. 

PMID- 24852890
TI  - Influenza and other respiratory virus infections in outpatients with medically
      attended acute respiratory infection during the 2011-12 influenza season.
AB  - BACKGROUND: Respiratory tract infections are a major cause of outpatient visits,
      yet only a portion is tested to determine the etiologic organism. Multiplex
      reverse transcriptase polymerase chain reaction (MRT-PCR) assays for detection of
      multiple viruses are being used increasingly in clinical settings. METHODS:
      During January-April 2012, outpatients with acute respiratory illness (<= 7 days)
      were tested for influenza using singleplex RT-PCR (SRT-PCR). A subset was assayed
      for 18 viruses using MRT-PCR to compare detection of influenza and examine the
      distribution of viruses and characteristics of patients using multinomial
      logistic regression. RESULTS: Among 662 participants (6 months-82 years),
      detection of influenza was similar between the MRT-PCR and SRT-PCR (kappa =
      0.83). No virus was identified in 267 (40.3%) samples. Commonly detected viruses
      were human rhinovirus (HRV, 15.4%), coronavirus (CoV, 10.4%), respiratory
      syncytial virus (RSV, 8.4%), human metapneumovirus (hMPV, 8.3%), and influenza
      (6%). Co-detections were infrequent (6.9%) and most commonly occurred among those
      <18 years old. In regression analyses, compared with non-viral illnesses, RSV and
      hMPV were significantly more frequent in children and less frequent in 18- to 49
      year-olds than in those >= 50 years (P = 0.01), fever was more common in hMPV and
      influenza infections (P = 0.008), nasal congestion was more frequent in CoV, HRV,
      hMPV, influenza and RSV infections (P = 0.001), and body mass index was higher
      among those with influenza (P = 0.036). CONCLUSIONS: Using MRT-PCR, a viral
      etiology was found in three-fifths of patients with medically attended outpatient
      visits for acute respiratory illness during the influenza season; co-detected
      viruses were infrequent. Symptoms varied by viral etiology.

PMID- 24852891
TI  - Imaging in endometrial cancer.
AB  - The prognosis for women with endometrial cancer is generally good. This is
      because the disease is often diagnosed at an early treatable stage, as women seek
      care owing to postmenopausal bleeding. The prognosis is, however, worse for women
      with high-risk endometrial cancer. These women may benefit from more extensive
      surgery, including pelvic- and para-aortic lymph-node dissection, whereas such
      surgery is of no benefit for women with low-risk cancer. It is, therefore,
      important to correctly identify women with high-risk cancer before surgery. No
      consensus has been reached on how and when to use imaging to assess local
      extension of the disease. Nevertheless, evidence shows that imaging will improve
      the identification of women with high-risk cancer. The primary aim of this review
      is to present the examination technique, accuracy, imaging findings, benefits,
      and shortcomings of ultrasound and magnetic resonance imaging in the assessment
      of local tumour extension, in women with endometrial cancer. A secondary goal is
      to discuss the role of positron emission tomography and computed tomography,
      diagnostic modalities that primarily are used to detect lymph node and distant
      metastasis. 

PMID- 24852887
TI  - Context-dependent signal integration by the GLI code: the oncogenic load,
      pathways, modifiers and implications for cancer therapy.
AB  - Canonical Hedgehog (HH) signaling leads to the regulation of the GLI code: the
      sum of all positive and negative functions of all GLI proteins. In humans, the
      three GLI factors encode context-dependent activities with GLI1 being mostly an
      activator and GLI3 often a repressor. Modulation of GLI activity occurs at
      multiple levels, including by co-factors and by direct modification of GLI
      structure. Surprisingly, the GLI proteins, and thus the GLI code, is also
      regulated by multiple inputs beyond HH signaling. In normal development and
      homeostasis these include a multitude of signaling pathways that regulate proto
      oncogenes, which boost positive GLI function, as well as tumor suppressors, which
      restrict positive GLI activity. In cancer, the acquisition of oncogenic mutations
      and the loss of tumor suppressors - the oncogenic load - regulates the GLI code
      toward progressively more activating states. The fine and reversible balance of
      GLI activating GLI(A) and GLI repressing GLI(R) states is lost in cancer. Here,
      the acquisition of GLI(A) levels above a given threshold is predicted to lead to
      advanced malignant stages. In this review we highlight the concepts of the GLI
      code, the oncogenic load, the context-dependency of GLI action, and different
      modes of signaling integration such as that of HH and EGF. Targeting the GLI code
      directly or indirectly promises therapeutic benefits beyond the direct blockade
      of individual pathways. 

PMID- 24852892
TI  - Hyperthermia sensitization and proton beam triggered liposomal drug release for
      targeted tumor therapy.
AB  - PURPOSE: The objectives of this study were to: 1) determine if mild hyperthermia
      (40-42 degrees C) can sensitize tumor cells for more effective proton beam
      radiotherapy (PBRT); 2) characterize the survival fraction of cells exposed to
      PBRT; and 3) characterize release of the drug doxorubicin (Dox) from low
      temperature sensitive liposomes (LTSLs) without exposure to mild hyperthermia in
      combination with PBRT. METHODS: Dox was actively loaded in LTSLs. A549 monolayer
      cells were incubated with 100-200 nM of Dox-LTSL (+/-mild hyperthermia). Cell
      irradiation (0-6 Gy) was performed by placing the cell culture plates inside a
      solid water phantom and using a clinical proton treatment beam with energy of 150
      MeV. End points were survival fraction, radiation-mediated Dox release, and
      reactive oxygen species (ROS) production. RESULTS: Hyperthermia effectively
      sensitized cells for PBRT and lowered the cell survival fraction (SF) by an
      average of 9.5%. The combination of 100 nM Dox-LTSL and PBRT (1-6 Gy) achieved
      additive to synergistic response at various dose combinations. At higher
      radiation doses (>3 Gy), the SF in the Dox and Dox-LTSL groups was similar
      (~20%), even in the absence of hyperthermia. In addition, 30% of the Dox was
      released from LTSLs and a 1.3-1.6 fold increase in ROS level occurred compared to
      LTSL alone therapy. CONCLUSIONS: The combination of LTSLs and PBRT achieves
      additive to synergistic effect at various dose combinations in vitro. Concurrent
      PBRT and Dox-LTSL treatment significantly improved the cytotoxic outcomes of the
      treatment compared to PBRT and Dox chemotherapy without LTSLs. We hypothesize
      that PBRT may induce drug release from LTSL in the absence of hyperthermia.

PMID- 24852893
TI  - A new twist in the old story-can compression induce mixing of phase separated
      solid dispersions? A case study of spray-dried miconazole-PVP VA64 solid
      dispersions.
AB  - PURPOSE: The phase response of Miconazole-PVP VA64 solid dispersions upon
      compression was investigated. This would allow understanding the phase behavior
      of these solid dispersions upon application of a different kind of stress (other
      than humidity and temperature) and ultimately lead to mechanistic perception of
      the phase changes taking place. METHODS: Miconazole and PVP VA64 were chosen as a
      model drug and polymer, respectively and solid dispersions were prepared by spray
      drying. Dried solid dispersions were compressed using different compression
      pressure but constant dwell time. MDSC and XRPD were used to characterize and
      study the effect of compression on the system. RESULTS: The solid dispersions
      showed a single Tg till 20% drug loading after which two Tg's were observed.
      Application of compression to the phase separated 30 and 40% compositions induced
      mixing resulting in only a single Tg. This reduction in number of Tg's upon
      compression is a result of mixing which can be attributed to polymer flow
      resulting in reduction of the domain size of different phases in the solid
      dispersions. CONCLUSIONS: Application of compression can influence the phase
      behavior of Miconazole-PVP VA64 solid dispersions. This observation may have
      drastic impact on the formulation development approach for solid dispersions to
      be administered as tablets.

PMID- 24852894
TI  - Dissolution testing of powders for inhalation: influence of particle deposition
      and modeling of dissolution profiles.
AB  - PURPOSE: The aim of this study was to investigate influencing factors on the
      dissolution test for powders for pulmonary delivery with USP apparatus 2 (paddle
      apparatus). METHODS: We investigated the influence of dose collection method,
      membrane holder type and the presence of surfactants on the dissolution process.
      Furthermore, we modeled the in vitro dissolution process to identify influencing
      factors on the dissolution process of inhaled formulations based on the Nernst
      Brunner equation. RESULTS: A homogenous distribution of the powder was required
      to eliminate mass dependent dissolution profiles. This was also found by modeling
      the dissolution process under ideal conditions. Additionally, it could be shown
      that influence on the diffusion pathway depends on the solubility of the
      substance. CONCLUSION: We demonstrated that the use of 0.02% DPPC in the
      dissolution media results in the most discriminating and reproducible dissolution
      profiles. In the model section we demonstrated that the dissolution process
      depends strongly on saturation solubility and particle size. Under defined
      assumptions we were able show that the model is predicting the experimental
      dissolution profiles.

PMID- 24852895
TI  - Interspecies pharmacokinetic modeling of subcutaneous absorption of rituximab in
      mice and rats.
AB  - PURPOSE: To investigate the effect of dose level and anatomical site of injection
      on the pharmacokinetics of rituximab in mice, and to evaluate the utility of a
      pharmacokinetic model for describing interspecies differences in subcutaneous
      absorption between mice and rats. METHODS: Rituximab serum concentrations were
      measured following intravenous and subcutaneous administration at the back and
      abdomen of mice. Several approaches were compared for scaling model parameters
      from estimated values in rats. RESULTS: The bioavailability of rituximab
      following subcutaneous injection was inversely related to the dose level and was
      dependent on the site of injection in mice. The overall rate of absorption was
      faster in mice as compared to rats. Subcutaneous absorption profiles were well
      described using the proposed structural model, in which the total receptor
      concentration, the affinity of rituximab to the receptor, and the degradation
      rate constant were assumed to be species independent. CONCLUSIONS: Subcutaneous
      absorption processes show similar trends in rats and mice, although the magnitude
      differs between species. A mathematical model that combines the absorption of
      free and bound antibody with presystemic degradation successfully captured
      rituximab pharmacokinetics in both species, and approaches for sharing and
      scaling parameters between species were identified.

PMID- 24852897
TI  - Reversible sigma C-C bond formation between phenanthroline ligands activated by
      (C5Me5)2Yb.
AB  - The electronic structure and associated magnetic properties of the 1,10
      phenanthroline adducts of Cp*2Yb are dramatically different from those of the
      2,2'-bipyridine adducts. The monomeric phenanthroline adducts are ground state
      triplets that are based upon trivalent Yb(III), f(13), and (phen(*-) ) that are
      only weakly exchange coupled, which is in contrast to the bipyridine adducts
      whose ground states are multiconfigurational, open-shell singlets in which
      ytterbium is intermediate valent ( J. Am. Chem. Soc 2009 , 131 , 6480 ; J. Am.
      Chem. Soc 2010 , 132 , 17537 ). The origin of these different physical properties
      is traced to the number and symmetry of the LUMO and LUMO+1 of the heterocyclic
      diimine ligands. The bipy(*-) has only one pi*1 orbital of b1 symmetry of
      accessible energy, but phen(*-) has two pi* orbitals of b1 and a2 symmetry that
      are energetically accessible. The carbon ppi-orbitals have different nodal
      properties and coefficients and their energies, and therefore their populations
      change depending on the position and number of methyl substitutions on the ring.
      A chemical ramification of the change in electronic structure is that
      Cp*2Yb(phen) is a dimer when crystallized from toluene solution, but a monomer
      when sublimed at 180-190  degrees C. When 3,8-Me2phenanthroline is used, the
      adduct Cp*2Yb(3,8-Me2phen) exists in the solution in a dimer-monomer equilibrium
      in which DeltaG is near zero. The adducts with 3-Me, 4-Me, 5-Me, 3,8-Me2, and 5,6
      Me2-phenanthroline are isolated and characterized by solid state X-ray
      crystallography, magnetic susceptibility and LIII-edge XANES spectroscopy as a
      function of temperature and variable-temperature (1)H NMR spectroscopy. 

PMID- 24852896
TI  - Controlled delivery of fibroblast growth factor-9 from biodegradable poly(ester
      amide) fibers for building functional neovasculature.
AB  - PURPOSE: For building functional vasculature, controlled delivery of fibroblast
      growth factor-9 (FGF9) from electrospun fibers is an appealing strategy to
      overcome challenges associated with its short half-life. FGF9 sustained delivery
      could potentially drive muscularization of angiogenic sprouts and help regenerate
      stable functional neovasculature in ischemic vascular disease patients. METHODS:
      Electrospinning parameters of FGF9-loaded poly(ester amide) (PEA) fibers have
      been optimized, using blend and emulsion electrospinning techniques. In vitro PEA
      matrix degradation, biocompatibility, FGF9 release kinetics, and bioactivity of
      the released FGF9 were evaluated. qPCR was employed to evaluate platelet-derived
      growth factor receptor-beta (PDGFRbeta) gene expression in NIH-3T3 fibroblasts,
      10T1/2 cells, and human coronary artery smooth muscle cells cultured on PEA
      fibers at different FGF9 concentrations. RESULTS: Loaded PEA fibers exhibited
      controlled release of FGF9 over 28 days with limited burst effect while
      preserving FGF9 bioactivity. FGF9-loaded and unloaded electrospun fibers were
      found to support the proliferation of fibroblasts for five days even in serum
      depleted conditions. Cells cultured on FGF9-supplemented PEA mats resulted in
      upregulation of PDGFRbeta in concentration and cell type-dependent manner.
      CONCLUSION: This study supports the premise of controlled delivery of FGF9 from
      PEA electrospun fibers for potential therapeutic angiogenesis applications.

PMID- 24852898
TI  - Trigeminal nerve stimulation does not acutely affect cortical excitability in
      healthy subjects.
AB  - BACKGROUND: Trigeminal nerve stimulation (TNS) has recently emerged as a new
      therapeutic option for patients with drug-resistant epilepsy but its potential
      mechanisms of action are not known. Since other antiepileptic treatments have
      been shown to alter cortical excitability, thereby reducing the liability to
      seizures, it has been suggested that cranial nerve stimulation such as TNS may
      act in the same way. OBJECTIVE: To study whether TNS has the potential to alter
      cortical excitability in healthy subjects. METHODS: An adaptive paired-pulse
      transcranial magnetic stimulation protocol stimulating the dominant hand motor
      area was used to measure resting motor threshold (rMT), short-interval
      intracortical inhibition (SICI), intracortical facilitation (ICF) and long
      interval intracortical inhibition (LICI) before, during, and after 40 min of 120
      Hz bilateral external continuous trigeminal nerve stimulation. Neuronavigation
      was used for guidance. RESULTS: TNS was well tolerated by all subjects. No
      significant changes were seen in the parameters studied. CONCLUSION: Unlike for
      example anti-epileptic drugs and the ketogenic diet, trigeminal nerve stimulation
      does not seem to alter cortical excitability in healthy subjects. This is the
      first study on cortical excitability in relation to continuous trigeminal nerve
      stimulation. It still remains to be proven that TNS has the prerequisites to
      effectively counteract epileptic events in humans.

PMID- 24852899
TI  - Self-assembly of graphene oxide at interfaces.
AB  - Due to its amphiphilic property, graphene oxide (GO) can achieve a variety of
      nanostructures with different morphologies (for example membranes, hydrogel,
      crumpled particles, hollow spheres, sack-cargo particles, Pickering emulsions,
      and so on) by self-assembly. The self-assembly is mostly derived from the self
      concentration of GO sheets at various interfaces, including liquid-air, liquid
      liquid and liquid-solid interfaces. This paper gives a comprehensive review of
      these assembly phenomena of GO at the three types of interfaces, the derived
      interfacial self-assembly techniques, and the as-obtained assembled materials and
      their properties. The interfacial self-assembly of GO, enabled by its fantastic
      features including the amphiphilicity, the negatively charged nature, abundant
      oxygen-containing groups and two-dimensional flexibility, is highlighted as an
      easy and well-controlled strategy for the design and preparation of
      functionalized carbon materials, and the use of self-assembly for uniform
      hybridization is addressed for preparing hybrid carbon materials with various
      functions. A number of new exciting and potential applications are also presented
      for the assembled GO-based materials. This contribution concludes with some
      personal perspectives on future challenges before interfacial self-assembly may
      become a major strategy for the application-targeted design and preparation of
      functionalized carbon materials. 

PMID- 24852900
TI  - All-inorganic nanocrystals as a glue for BiSbTe grains: design of interfaces in
      mesostructured thermoelectric materials.
AB  - Nano- and mesostructuring is widely used in thermoelectric (TE) materials. It
      introduces numerous interfaces and grain boundaries that scatter phonons and
      decrease thermal conductivity. A new approach has been developed for the rational
      design of the interfaces in TE materials by using all-inorganic nanocrystals
      (NCs) that serve as a "glue" for mesoscopic grains. For example, circa 10 nm Bi
      NCs capped with (N2H5)4Sb2Te7 chalcogenidometallate ligands can be used as an
      additive to BiSbTe particles. During heat treatment, NCs fill up the voids
      between particles and act as a "glue", joining grains in hot-pressed pellets or
      solution-processed films. The chemical design of NC glue allowed the selective
      enhancement or decrease of the majority-carrier concentration near the grain
      boundaries, and thus resulted in doped or de-doped interfaces in granular TE
      material. Chemically engineered interfaces can be used as to optimize power
      factor and thermal conductivity.

PMID- 24852901
TI  - Use of external ventriculostomy and intrathecal anti-fungal treatment in cerebral
      mucormycotic abscess.
AB  - Mucormycosis is an invasive fungal infection associated with a high mortality.
      Cerebral mucor abscesses can result secondary to rhinocerebral or hematogenous
      spread. Amphotericin B, posaconazole, and aggressive surgical resection are the
      hallmarks of treatment. While amphotericin is typically administered
      intravenously, less is known about the use of intrathecal amphotericin B. We
      describe a 42-year-old man who developed a cerebellar mucor abscess after
      undergoing hematopoietic stem cell transplant for the treatment of
      myelodysplastic syndrome. In the post-operative period he was admitted to the
      neurocritical care unit and received liposomal amphotericin B intravenously and
      through an external ventricular drain. This patient demonstrates that utilization
      of an external ventricular drain for intrathecal antifungal therapy in the post
      operative period may warrant further study in patients with difficult to treat
      intracranial fungal abscesses. 

PMID- 24852902
TI  - The effect of blood transfusion on short-term, perioperative outcomes in elective
      spine surgery.
AB  - Studies in various surgical procedures have shown that transfusion of red blood
      cells (RBC) increases the risk of postoperative morbidity and mortality. Impact
      of blood transfusion in patients undergoing spine surgery is not well-described.
      We assessed the impact of intra and postoperative transfusion on postoperative
      morbidity and mortality in patients undergoing elective spine surgery. We used
      the American College of Surgeons' National Surgical Quality Improvement Program
      to identify a retrospective cohort of 36,901 adult patients who underwent
      elective spine surgery between 2006 and 2011. Patients who received intra or
      postoperative transfusion (n=3262) were matched to those who did not using
      propensity scores. Logistic regression predicted adverse postoperative outcomes.
      We conducted sensitivity analysis in a subset of patients in whom the number of
      intraoperatively transfused units of RBC or whole blood was known. Upon matching,
      preoperative hematocrit, length of surgery, and percentage of spinal fusion
      surgery were not significantly different between transfused and non-transfused
      patients. After matching, transfusion remained adversely associated with
      prolonged length of stay (LOS) in hospital (odds ratio [OR] 2.6, 95% confidence
      interval [CI] 2.3-2.9), postoperative complications (OR 1.6, 95% CI 1.4-1.9), and
      an increased 30 day return to operation room (OR 1.7, 95% CI 1.3-2.2).
      Transfusion of even one unit of blood intraoperatively was associated with
      prolonged LOS (OR 2.0, 95% CI 1.5-2.6) and minor complications (OR 2.4, 95% CI
      1.3-4.3). Therefore, transfusion of RBC or whole blood, even a single unit,
      increased LOS and postoperative morbidity in patients undergoing elective spine
      surgery, independent of preoperative hematocrit level and patient comorbidities.

PMID- 24852903
TI  - Outcomes and patterns of care in adult skull base chordomas from the
      Surveillance, Epidemiology, and End Results (SEER) database.
AB  - This study aims to demonstrate survival rates and treatment patterns among
      patients with chordomas of the skull base using a large population database.
      Patients with cranial chordomas between 1973 and 2009 were identified from the
      USA Surveillance, Epidemiology, and End Results (SEER) public use database.
      Kaplan-Meier analysis was used to examine the effect of surgery and radiation on
      overall survival. We identified 394 patients with histologically-confirmed
      cranial chordomas. Median survival was 151 months. Most patients (89.09%)
      underwent surgery. Less than half (44.92%) received radiation after diagnosis.
      Patients who underwent surgical resection survived significantly longer than
      those who did not undergo resection, regardless of other treatments (151 versus
      81 months, p<0.001). Ten year survival was lower among patients receiving
      radiation (44.8% versus 61.4%, p=0.66). Surgery predicted better overall survival
      by univariate analysis (hazard ratio [HR] 0.603, p=0.0293); younger age at
      diagnosis (HR 1.028, p<0.001), and later year of diagnosis (HR 0.971, p=0.0027)
      were prognostic of improved survival in a multivariate model. In subgroup
      analysis of patients with documented tumor size, smaller tumor size (HR 1.021,
      p=0.0067), younger age (HR 1.031, p=0.001), and treatment within a higher volume
      registry (HR 0.490, p=0.0129) predicted improved survival. Surgical intervention
      offers survival benefit for cranial chordomas. Findings of decreased survival in
      patients receiving radiation may be associated with selection. Studies examining
      surgical extent of resection data and radiation details are needed to determine
      the impact of radiotherapy.

PMID- 24852904
TI  - Cryoglobulinemic vasculitis in a patient with CREST syndrome.
AB  - Cryoglobulinemic vasculitis is a rare entity. Although it has been reported in
      diffuse systemic sclerosis, it has not been reported in calcinosis, Raynaud's
      phenomenon, esophageal dysmotility, sclerodactyly and telangiectasia (CREST)
      syndrome. We report a patient with cryoglobulinemic vasculitis with CREST
      syndrome who did not have typical clinical features of vasculitis. This 58-year
      old woman presented with mild generalized weakness and a diagnosis of CREST
      syndrome, which included Raynaud's syndrome, dysphagia and telangiectasias. She
      was positive for serum cryoglobulins, which led to a sural nerve biopsy. The
      biopsy results were consistent with cryoglobulinemic vasculitis. Cryoglobulinemic
      vasculitis has not been previously reported in CREST syndrome to our knowledge.
      Additionally, the patient also had limited clinical symptoms. Our patient
      displays the importance of checking for cryoglobulins and obtaining a nerve
      biopsy when the serum is positive. Both of these diagnostic tests were integral
      for directing appropriate treatment for this patient. 

PMID- 24852905
TI  - Dissociation of severity of stroke and aphasia recovery early after intravenous
      recombinant tissue plasminogen activator thrombolysis.
AB  - Clinical observation suggested to us that aphasia recovers relatively better than
      other deficits early after intravenous recombinant tissue plasminogen activator
      (IV-rtPA) treatment in stroke patients with minor deficits, while the reverse
      seemed the case in those with severe deficits. Retrospective analysis of acute
      ischemic stroke patients with aphasia admitted within 3 hours from symptom onset
      and treated with IV-rtPA was carried out. Stroke severity, aphasia and global
      neurological impairment were assessed at admission and 24 hours after
      thrombolysis. Improvement of aphasia (gain of ? 1 point on the National
      Institutes of Health Stroke Scale [NIHSS] aphasia score) and global neurological
      improvement (gain of ? 4 points on the NIHSS) were compared in minor strokes
      (NIHSS ? 7), moderate strokes (NIHSS 8-15), and major strokes (NIH ? 16). Sixty
      nine of 243 stroke patients suffered from aphasia. Improvement of aphasia
      occurred in 7/16 minor strokes, 11/25 moderate strokes, and 7/28 severe strokes.
      Improvement of ? 4 points on the NIHSS occurred in 3/16 minor strokes, 17/25
      moderate strokes and 15/28 severe strokes. There is a significant (X(2)=4.073,
      p<0.05) dissociation of recovery of aphasia and that of other neurological
      deficits between minor versus severe strokes. This confirms the clinically
      suspected dissociation between a good early recovery from aphasia in minor
      strokes relative to recovery of other neurological deficits, as opposed to a
      better recovery from other neurological deficits than from aphasia in patients
      with severe strokes.

PMID- 24852906
TI  - [Steroid 21-hydroxylase deficiencies and female infertility: pathophysiology and
      management].
AB  - Steroid 21-hydroxylase deficiency is the most common adrenal genetic disease and
      is also named congenital adrenal hyperplasia. Depending on the severity of
      CYP21A2 gene mutations, there are severe or "classical" forms and moderate or
      "nonclassical" forms of 21-hydroxylase deficiency. The enzyme deficiency causes a
      disruption of adrenal steroidogenesis, which induces hyperandrogenism and
      elevated plasma levels of progesterone and 17-hydroxyprogesterone, the two
      substrates of 21-hydroxylase. These endocrine abnormalities will disrupt gonadal
      axis, endometrial growth and maturation and finally secretion of cervical mucus.
      All these phenomena contribute to a female hypofertility. Infertility is more
      severe in classical forms. When to become pregnant, treatment with hydrocortisone
      or dexamethasone can limit the production of adrenal androgens and progesterone
      and improves spontaneous pregnancy rates while minimizing the risk of
      miscarriage, which is usually relatively high in this disease. When planning
      pregnancy in patients with a 21-hydroxylase deficiency, genotyping the partner is
      required to screen for heterozygozity (1/50) and to assess the risk of
      transmission of a classical form in the progeny. 

PMID- 24852907
TI  - [Laparoscopic promontofixation: defining early morbidity using a standardized
      method].
AB  - OBJECTIVE: Adverse event reporting for laparoscopic promontofixation is highly
      variable and non-standardized in the literature. The aim of this study was to
      better characterize early postoperative complications of laparoscopic
      promontofixation for genital prolapse using a standardized reporting methodology.
      PATIENTS AND METHODS: A retrospective study was conducted on 174 women with
      genital prolapse undergoing laparoscopic promontofixation from January 2008 to
      January 2013. Complications arising during the first month after surgery were
      reviewed according to the Clavien and Dindo classification. RESULTS: At least one
      postoperative adverse event was reported in 57 out of 174 (33 %) women, grade 1
      in 22 patients (13 %), grade 2 in 31 patients (18 %) and grade 3 in 4 patients (2
      %). No patient experienced a grade 4 or 5 complication. Fifty-three out of 57 (93
      %) complications were grade 1 or 2. The most frequently reported adverse event
      (n=24; 14 %) was constipation (grade 2). DISCUSSION AND CONCLUSION: Laparoscopic
      promontofixation is a safe procedure with almost exclusively benign (grade 1 or
      2) early complications. The hypothesis of induction or increasing constipation by
      this type of genital prolapse surgery should be further evaluated.

PMID- 24852908
TI  - [Selective termination of pregnancy for monochorionic twins: a national survey of
      professional practice].
AB  - OBJECTIVES: Selective Termination of Pregnancy (STOP) for discordant fetal
      condition in monochorionic twin pregnancy is a rarely performed procedure raising
      technical and ethical considerations. There are no epidemiological data available
      in France concerning STOP and no guideline or scientific consensus on how or when
      to perform has been published. MATERIALS AND METHODS: We conducted a study of
      national practice using a declarative questionnaire sent by e-mail to each
      medical coordinator of every 48 Multidisciplinary Center for Prenatal Diagnosis
      in France. The questions focused on the issues of 2010 and 2011. Two reminders
      were sent in case of no answer. RESULTS: The response rate to the questionnaire
      was 56 %; 81 % of centers have experienced at least once during the two years
      2010-2011 a discordant fetal anomaly in monochorionic twin pregnancy. Only 59 %
      of centers perform all the techniques of STOP. When interruption of the umbilical
      blood flow is considered, bipolar forceps coagulation is the most used (75 %).
      Achieving STOP during a cesarean section is a common practice (75 % of centers).
      Locoregional anesthesia is the preferred mode of anesthesia for STOP. DISCUSSION
      AND CONCLUSION: STOP on monochorionic twin pregnancy is not practiced in all
      Multidisciplinary Center for Prenatal Diagnosis in France. The most widely
      practiced and most studied technique is bipolar forceps coagulation. The option
      of an expectant management should always be considered and its risks should be
      balanced with those of STOP. The practice of STOP during cesarean section is not
      unusual.

PMID- 24852909
TI  - [Delayed necrotizing fasciitis: a complication of stress incontinence surgery by
      suburethral sling].
AB  - We report a 50-year-old woman case with an extensive necrotizing fasciitis (NF).
      The NF appeared 10 years after a tension free vaginal tape procedure for urinary
      stress incontinence. Vital prognosis was engaged due to the initial sepsis
      severity. This kind of complication is rare and could be under estimated. NF
      usually appear soon after surgery, whatever within the year following
      implantation. Anyway, NF are always related to a vaginal erosion of the tape.

PMID- 24852910
TI  - [Unilateral gigantomastia of pregnancy: case-report of a giant breast hamartoma].
AB  - Breast hamartoma is a benign tumour consisting of fat, fibrous and glandular
      tissue. A young woman in her 19th week of pregnancy underwent exceptional surgery
      for a unilateral gigantomastia secondary to a rapid-growth giant hamartoma during
      her second pregnancy. Rigourous clinical and ultrasonographic examinations were
      performed followed by multiple biopsies. The decision to perform surgery was
      guided by the risk to skin integrity and of tumour infarct. Our report provides
      detailed information on gestational benign breast tumours, on the specificities
      of medical imaging and breast surgery in pregnant patients. 

PMID- 24852911
TI  - [Umbilical vein varix thrombosis].
AB  - Umbilical vein varix is a rare entity, which can lead to in utero fetal death. We
      report the case of a women diagnosed with umbilical vein varix on the 31st week
      of amenorrhea. A close follow-up and the early diagnosis of umbilical vein
      thrombosis have allowed the patient to give birth to a healthy newborn on the
      34th week of amenorrhea. Improved ultrasound imaging as well as systematic study
      of fetal annexes lead to an early diagnosis of umbilical vein abnormalities. This
      allows a close follow-up and an early diagnosis of fetal life-threatening
      complications. 

PMID- 24852912
TI  - [MRI-guided breast microbiospy or macrobiopsy: which is the best option for a
      small tumor?].
AB  - The choice of the optimum therapeutic strategy for breast cancer depends on the
      histological diagnosis of the sample obtained by biopsy. The microbiopsy is the
      preferred method as it provides an accurate diagnosis of the histological type as
      well as the main prognostic factors, whilst being simple, fast and inexepensive.
      However, some infraclinic breast tumors are not accessible by conventional
      guidance due to excessive depth inside the breast, their small size or technical
      inability to image them by mammography or ultrasonography. In those cases, the
      MRI guidance may help to perform the biopsy. Most MRI biopsies are made by large
      core needle that are known to alter the histological structure of the tumor and
      to disturb the anatomopatholgical analysis (size and surgical margin). Those are
      very important elements to know before treatment. Our case report details an
      original technique of MRI microbiopsy of a deep 4mm opacity found on the occasion
      of a patient's mammography. The operative specimen revealed an invasive ductal
      carcinoma of 4mm diameter which scored III on the Elston and Ellis scale
      (oestrogen and progesterone receptors tested negative and HER-2 was over
      expressed). It was associated with a high grade in situ ductal carcinoma. No
      systemic treatment was prescribed due to the small size of the carcinoma. The
      development of partially or totally amagnetic microbiopsy pistols would help
      perform microbiopses guided by MRI. 

PMID- 24852913
TI  - Toxicity of imine-iminium dyes and pigments: electron transfer, radicals,
      oxidative stress and other physiological effects.
AB  - Although conjugation is well known as an important contributor to color, there is
      scant recognition concerning involvement of imine and iminium functions in the
      physiological effects of this class of dyes and pigments. The group includes the
      dyes methylene blue, rhodamine, malachite green, fuchsin, crystal violet,
      auramine and cyanins, in addition to the pigments consisting of pyocyanine,
      phthalocyanine and pheophytin. The physiological effects consist of both toxicity
      and beneficial aspects. The unifying theme of electron transfer-reactive oxygen
      species-oxidative stress is used as the rationale in both cases. Toxicity is
      frequently prevented or alleviated by antioxidants. The apparent dichotomy of
      methylene blue action as both oxidant and antioxidant is rationalized based on
      similar previous cases. This mechanistic approach may have practical benefit.
      This review is important in conveying, for the first time, a unifying mechanism
      for toxicity based on electron transfer-reactive oxygen species-oxidative stress
      arising from imine-iminium.

PMID- 24852914
TI  - Effects of healthy aging on the cardiopulmonary hemodynamic response to exercise.
AB  - This study aimed to define the influence of healthy aging on the central
      hemodynamic response to exercise. Advancing age results in numerous alterations
      to the cardiovascular system and is a major risk factor to develop heart failure.
      In patients with suspected heart failure with preserved ejection fraction, there
      is an increasing interest in the incorporation of stress hemodynamic studies into
      the diagnostic evaluation pathway. However, many patients with suspected heart
      failure with preserved ejection fraction are older, and there are few data
      regarding the effect of aging on the normal central hemodynamic responses to
      exercise. Therefore, we examined 55 healthy patients using right-sided cardiac
      catheterization with exercise. Mean age was 49.6 years, with 36% older than 55
      years. On exercise, the mean pulmonary artery pressure was higher with advancing
      age (r = 0.412, p = 0.002). Additionally, age was negatively associated with
      cardiac index (r = 0.407, p = 0.005). The exercise-induced rise in pulmonary
      capillary wedge pressure (r = 0.378, p = 0.004) was greater with advancing age.
      Pulse pressure measured during exercise (r = 0.541, p <0.01) increased with age,
      as did diastolic dysfunction assessed by E/A ratio (r = 0.569, p <0.001). In
      conclusion, aging was associated with decreased cardiac output and increased
      pulmonary artery pressure during exercise, which developed as the consequence of
      both increased pulmonary vasculature resistance and higher left ventricular
      filling pressures. 

PMID- 24852915
TI  - Relation of T-wave alternans to mortality and nonsustained ventricular
      tachycardia in patients with non-ST-segment elevation acute coronary syndrome
      from the MERLIN-TIMI 36 trial of ranolazine versus placebo.
AB  - We explored the utility of T-wave alternans (TWA) in predicting mortality in
      patients with non-ST-segment elevation acute coronary syndrome (NSTEACS). Maximum
      TWA was calculated using Modified Moving Average method from continuous
      electrocardiographic recordings in patients with left ventricular ejection
      fraction <40% and ventricular tachycardia (VT) >=4 beats during index
      hospitalization or sudden cardiac death during the follow-up year and age- and
      sex-matched controls in the Metabolic Efficiency with Ranolazine for Less
      Ischemia in Non-ST Elevation Acute Coronary Syndrome-Thrombolysis In Myocardial
      Infarction (MERLIN-TIMI) 36 trial. All patients received standard therapy for
      NSTEACS plus ranolazine (n = 109) or placebo (n = 101). Median follow-up was 1
      year. Baseline clinical characteristics did not differ between patients with
      elevated TWA (>=47 MUV) compared with lower levels. Patients with TWA >=47 MUV at
      admission had increased risk of total mortality (adjusted odds ratio [ORadj]
      2.35, p = 0.04) during follow-up and VT >=4 beats (ORadj 2.70, p = 0.01) during
      hospitalization with a trend toward increased cardiovascular death risk (ORadj
      2.18, p = 0.07) during follow-up. In patients receiving placebo, TWA >=47 MUV on
      day 6 was associated with increased risk of total mortality (OR 4.12, 95%
      confidence interval 1.25 to 13.64, p = 0.02) and cardiovascular death (OR 4.73, p
      = 0.01) during follow-up. No deaths occurred among patients with TWA >=47 MUV
      assigned to ranolazine. In conclusion, in patients with NSTEACS and left
      ventricular ejection fraction <40%, TWA >=47 MUV early after admission is
      associated with increased risk of mortality at 1 year and with nonsustained VT
      during hospitalization. TWA may be useful in risk estimation in patients with
      NSTEACS. The possibility that TWA may serve as a therapeutic target deserves
      further exploration. 

PMID- 24852916
TI  - Usefulness of hyponatremia as a predictor for adverse events in patients with
      heart failure receiving cardiac resynchronization therapy.
AB  - Hyponatremia portends a poor prognosis in patients with heart failure (HF). The
      aim of this study was to evaluate prognostic implication of hyponatremia on
      adverse events in patients with HF receiving cardiac resynchronization therapy
      (CRT). Additionally, the impact of improvement of hyponatremia after CRT device
      implantation was also evaluated. In this retrospective analysis, we included
      patients in whom a CRT device was implanted between April 2004 and April 2010 at
      our institution and had a baseline sodium level obtained within 72 hours of
      implantation. The patients were followed up for 3 years after implantation for
      subsequent primary composite end points, that is, hospitalization for HF, left
      ventricular assist device or heart transplant, and all-cause death. Sodium levels
      were followed up at 3 to 6 months after device implantation. Hyponatremia was
      defined as a serum sodium level of <135 mmol/L. A total of 402 patients were
      included (age 68.7 +/- 12.3 years, women 20.9%). One hundred seventy-nine adverse
      events were noted in this period. In a Cox proportional hazards univariate model,
      hyponatremia (hazard ratio [HR] 1.54, 95% confidence interval [CI] 1.113 to
      2.131, p = 0.009), creatinine (HR 1.267, 95% CI 1.156 to 1.389, p <0.001), and
      diuretics (HR 2.652, 95% CI 1.401 to 5.019, p = 0.003) were associated with
      occurrence of the composite end point. A total of 57.9% of patients with
      hyponatremia at baseline had the composite end point compared with 40.7% of those
      with normal sodium concentration (p = 0.004). Kaplan-Meier curve showed that
      hyponatremic patients fared worse. Also, patients in whom hyponatremia resolved
      after CRT device implantation had lower incidence of the composite end point
      compared with patients who had normal pre-CRT sodium levels but developed
      hyponatremia later. In conclusion, baseline hyponatremia is associated with poor
      prognosis in patients with HF. CRT can resolve hyponatremia in some patients
      after device implantation. Patients with postimplantation hyponatremia (either
      newly developed or persistent from baseline) have a poor clinical outcome. Post
      CRT improvement of hyponatremia is associated with improved clinical outcomes. 

PMID- 24852917
TI  - External beam radiation with 'curative intent' in advanced ovarian cancer: an
      uncommon but rational management approach based on the natural history of cancer
      in an individual patient.

PMID- 24852918
TI  - Multiple sclerosis, solitary sclerosis or something else?
AB  - BACKGROUND: Inflammatory demyelinating diseases of the central nervous system
      represent a wide spectrum of entities and their classification cannot currently
      be regarded complete. OBJECTIVE: Our aim is to describe a series of patients
      presenting with progressive myelopathy associated to a single demyelinating
      lesion of the spinal cord. METHODS: We identified the patients affected by
      chronic progressive spinal cord dysfunction related to a single spinal cord
      lesion not satisfying the diagnostic criteria for any of the currently defined
      diseases. RESULTS: Seven females and one male were included. The median age at
      onset of symptoms was 53 years (range 42-68) and the median follow-up was 8 years
      (range 5-12). Brain and spinal magnetic resonance imaging (MRI) scans detected
      only one single, circumscribed, T2 hyperintense, non-longitudinally extensive
      lesion at level of cervico-medullary junction or cervical cord, in the absence of
      Gadolinium enhancement or swelling. Cerebrospinal fluid (CSF) examination
      displayed neither oligoclonal bands nor raised IgG index. A response to
      immunosuppressive agents was observed in some of the patients. Serial control
      brain and spinal MRI did not reveal accumulation of new lesions. CONCLUSION: New
      entities or variants should be included among the inflammatory demyelinating
      diseases of the central nervous system, and their characterization may have
      relevant prognostic and treatment implications.

PMID- 24852919
TI  - Blood miRNA expression pattern is a possible risk marker for natalizumab
      associated progressive multifocal leukoencephalopathy in multiple sclerosis
      patients.
AB  - BACKGROUND: Natalizumab has shown its efficacy in reducing multiple sclerosis
      (MS) relapses and progression of disability; however, it has been associated with
      an increased risk of developing progressive multifocal leukoencephalopathy (PML).
      The differential expression of microRNA (miRNA), the small non-coding RNAs that
      regulate gene expression, in natalizumab-treated patients has been reported and
      miRNA have also been described as good candidates for disease biomarkers.
      OBJECTIVE: To characterize the effect of natalizumab therapy on the miRNA
      expression pattern and to search for miRNAs that can predict PML on an individual
      basis. METHODS: The expression of 754 microRNAs was measured in blood samples
      from 19 relapsing-remitting MS patients at three time points during natalizumab
      therapy, using TaqMan OpenArray panels. Two patients included in this study
      developed PML after more than 2 years of therapy. RESULTS: We found that the
      expression level of three miRNAs (let-7c, miR-125a-5p and miR-642) was affected
      after 6 months of therapy (t6). Furthermore, we observed a differential
      expression of another three miRNAs (miR-320, miR-320b and miR-629) between the
      PML and non-PML groups after 12 months of treatment (t12); and a positive
      correlation was found between therapy time and the expression of miR-320.
      CONCLUSIONS: Natalizumab modified the expression levels of three miRNAs after a 6
      month treatment. We suggest miR-320, miR-320b and miR-629 as possible biomarkers
      for individual PML risk assessment.

PMID- 24852920
TI  - Changes in cognition, arm function and lower body function after slow-release
      Fampridine treatment.
AB  - OBJECTIVE: We aimed to evaluate the effect of slow-release (SR) Fampridine on
      multiple outcome measures reflecting different domains, and to compare the
      responsiveness of the Six Spot Step Test (SSST) and the Timed 25 Foot Walk
      (T25FW). METHODS: For this study 108 participants were included. On day 0 they
      were tested with the T25FW, the SSST, the 9-Hole Peg Test (9-HPT), the 5 Times
      Sit-To-Stand test (5-STS) and the Symbol Digit Modalities Test (SDMT). Four weeks
      of treatment with SR Fampridine 10 mg BID was commenced. Participants were tested
      again after 26-28 days of treatment. RESULTS: Mean changes observed were: SSST 
      3.4+/-6.4 s (p<0.001), T25FW -1.2+/-3.7 s (p<0.001), 9-HPT -1.2+/-6.0 s
      (p<0.001), 5- STS -3.4+/-7.2 s (p<0.001) and SDMT 1.4+/-4.8 a.u. (p=0.003).
      Change on the SSST differed significantly from T25FW (SSST 17.0+/-19.6% vs. T25FW
      11.2+/-17.1%, p=0.0013). Some 48.6% were found to have a meaningful change on the
      SSST compared with 25.7% on the T25FW. The response to treatment with SR
      Fampridine did not correlate with age, sex, Expanded Disability Status Scale and
      disease duration. CONCLUSION: SR Fampridine treatment has significant effects on
      different domains including upper and lower body and cognition. Furthermore, the
      SSST is more responsive to the effect of SR Fampridine than is the T25FW.
      ClinicalTrials.gov identifier: NCT01656148.

PMID- 24852921
TI  - Multiphasic acute disseminated encephalomyelitis associated with atypical rubella
      virus infection.
AB  - We report the first case of an occurrence of multiphasic acute disseminated
      encephalomyelitis (ADEM) associated with atypical rubella virus infection with no
      rash and long-term increased titers of serum anti-rubella IgM in a 17-year-old
      male who had no history of rubella vaccination. He suffered from at least six
      clinical exacerbations with disseminated hyperintense lesions on FLAIR MR images
      during the course of 18 months. Repeated methylprednisolone pulse therapy and
      intravenous immunoglobulin therapy resolved the exacerbations. In patients with
      multiphasic ADEM of unknown etiology, clinicians should also consider the
      possibility of preceding infection with rubella virus. 

PMID- 24852922
TI  - Multiple deep white matter lesions mimic multiple sclerosis as an unusual
      complication of left atrial myxoma.
AB  - We report the case of a patient who developed right hemiparesis with an acute
      onset 2 weeks before being transferred to our hospital. The brain MRI revealed
      multiple lesions in deep white matter; some were ovoid and perpendicular to the
      lateral ventricle, typical of cerebral demyelinating disease such as multiple
      sclerosis. The patient reported no history of hypertension, diabetes,
      dyslipidemia or other conventional vascular risk factors. The initial diagnosis
      was clinically isolated syndrome. However, low fever and petechiae in the
      extremities developed during hospitalization, which reminded us of
      cardioembolism. Echocardiography finally revealed a left atrial myxoma. The
      patient's symptom alleviated after resection of the tumor. 

PMID- 24852923
TI  - Further investigation of safety monitoring guidelines based on magnetic resonance
      imaging lesion activity in multiple sclerosis clinical trials.
AB  - We assess two modified guidelines for monitoring patient safety in multiple
      sclerosis (MS) trials. These guidelines flag patients with an increase in
      contrast enhancing lesion (CEL) count above a threshold over the CEL level 1-2
      months earlier. We compare the new guidelines to the original guideline where the
      threshold is set according to the baseline by applying the guidelines to two
      previous studies. The odds ratios of a subsequent clinical relapse associated
      with meeting the CEL threshold based on the modified guidelines are similar to
      those based on the original guideline. There is a need for patient and cohort
      specific monitoring procedures. 

PMID- 24852924
TI  - Depression in multiple sclerosis: a long-term longitudinal study.
AB  - BACKGROUND: Depression is a common comorbidity in multiple sclerosis (MS), but
      little is known about its long-term prognosis. Depression in the general
      population is usually episodic with relatively short-lasting depressive episodes.
      In this study we investigate the long-term prognosis of depression in MS.
      METHODS: Using data from a large longitudinal observational study and from the
      Calgary MS clinic database, we investigated changes in Center for Epidemiological
      Studies Depression Scale (CESD) scores in MS patients over four years of follow
      up. We used logistic regression to investigate the association of the factors
      sex, age, disease duration, Expanded Disability Status Scale (EDSS), depression
      at baseline, and antidepressant use with depression at each year of follow-up.
      RESULTS: CESD scores remained largely stable, or decreased slightly over four
      years of follow-up, whereas EDSS scores steadily increased. Depression at
      baseline was the strongest predictor of depression at follow-up; the other
      factors were not or not consistently associated with depression at follow-up. As
      expected, antidepressant use was associated with a greater risk of depression at
      follow-up. Starting and stopping antidepressant treatment during follow-up was
      not associated with the risk of depression at follow-up or with significant
      change in CESD scores. CONCLUSION: In contrast to depression in the general
      population, depression in MS is largely chronic, which suggests a different
      pathophysiology.

PMID- 24852925
TI  - Extensive cerebral white matter involvement in a patient with NMO spectrum
      disorder.
AB  - Abnormal brain MRI has been described in up to 60% of patients with NMO patients.
      However, white matter T2 hyperintensities have been rarely observed. We report
      the case of a 49-year-old woman with long-lasting neuromyelitis optica (NMO)
      spectrum disorder and diffuse cerebral white matter T2-weighted hyperintensities.
      Our case suggests that some NMO patients can progressively develop l extensive
      cerebral involvement. 

PMID- 24852926
TI  - Multiple deep white matter lesions mimicking multiple sclerosis as an unusual
      complication of a left atrial myxoma.

PMID- 24852927
TI  - Multiple sclerosis in New Zealand Maori.
AB  - The prevalence of MS in New Zealand in 2006 was 73.2 (age standardized per
      100,000) while for those with indigenous Maori ancestry it was 3.6 times lower at
      20.6. Earlier regional surveys (1968-2001) all reported much lower, or zero,
      prevalence for Maori than European. There was no evidence for differences in MS
      between those with and without Maori ancestry in either clinical features or
      latitude, confirming that Maori ancestry does not produce the reported increase
      in prevalence with latitude. It is likely that prevalence is increasing in low
      risk Maori; however, MS prognosis is independent of Maori ancestry. 

PMID- 24852929
TI  - Bacterial diversity in soil from geophagic mining sites in the Qwa-Qwa region of
      South Africa.
AB  - Geophagia is practised in many parts of the world and can be associated with
      medicinal treatments, ceremonial events and spiritual behaviours/practices. This
      is the first report on a systematic investigation and description of the
      bacterial diversity in soil regularly ingested by geophagic individuals using a
      culture-independent method. Diversity in 17 different mining sites was
      investigated using denaturing gradient gel electrophoresis. Genetic material from
      Pantoea, Stenotrophomonas, Listeria, Rhodococcus and Sphingomonads was present in
      most of the soil samples. Species from these genera are recognised, potential or
      immerging human pathogens, and are of special interest in immune-compromised
      individuals. Other genera able to produce a variety of bacteriocins and
      antimicrobial/antifungal substances inhibitory towards food borne pathogens
      (Dactylosporangium and Bacillus) and able to degrade a range of environmental
      pollutants and toxins (Duganella and Massilia) were also present. These essential
      insights provide the platform for adjusting culturing strategies to isolate
      specific bacteria, further phylogenetic studies and microbial mining prospect for
      bacterial species of possible economic importance. 

PMID- 24852928
TI  - An observational comparison of natalizumab vs. fingolimod using JCV serology to
      determine therapy.
AB  - BACKGROUND: The lack of prospective trial data comparing certain multiple
      sclerosis (MS) therapies could be addressed with observational research.
      OBJECTIVE: The objective of this paper is to investigate outcomes of natalizumab
      versus fingolimod treatment in an MS cohort using a novel method of patient
      selection. METHODS: We reviewed entries from our clinic's database for all
      relapsing-remitting MS patients started on fingolimod and natalizumab where JCV
      serology was used to determine treatment. We analyzed each group for time to
      first relapse and in a second analysis, time to first relapse or gadolinium
      enhancing lesion. RESULTS: Sixty-nine patients on natalizumab and 36 on
      fingolimod met our inclusion criteria and had adequate follow-up for analysis.
      The baseline clinical characteristics at the time of treatment switch were
      similar. With a mean follow-up of 1.5 years for both treatment groups, there was
      a trend favoring natalizumab in time to first relapse, although this was not
      statistically significant (2.20 (0.87, 5.55) p = 0.095). There was a significant
      difference in the secondary outcome, time to relapse or gadolinium-enhancing
      lesion (2.31 (1.03, 5.17) p = 0.041), favoring natalizumab. Adjusted analyses
      favored natalizumab for both outcomes (p < 0.05). CONCLUSION: This work employed
      an observational study design where treatment allocation by JCV serology allowed
      for treatment groups with well-balanced characteristics.

PMID- 24852930
TI  - Controlled electrochemical carboxylation of graphene to create a versatile
      chemical platform for further functionalization.
AB  - An electrochemical approach is introduced for the versatile carboxylation of
      multi-layered graphene in 0.1 M Bu4NBF4/MeCN. First, the graphene substrate
      (i.e., graphene chemically vapor-deposited on Ni) is negatively charged at -1.9 V
      versus Ag/AgI in a degassed solution to allow for intercalation of Bu4N(+) and,
      thereby, separation of the individual graphene sheets. In the next step, the
      strongly activated and nucleophilic graphene is allowed to react with added
      carbon dioxide in an addition reaction, introducing carboxylate groups stabilized
      by Bu4N(+) already present. This procedure may be carried out repetitively to
      further enhance the carboxylation degree under controlled conditions.
      Encouragingly, the same degree of control is even attainable, if the
      intercalation and carboxylation is carried out simultaneously in a one-step
      procedure, consisting of simply electrolyzing in a CO2-saturated solution at the
      graphene electrode for a given time. The same functionalization degree is
      obtained for all multi-layered regions, independent of the number of graphene
      sheets, which is due to the fact that the entire graphene structure is opened in
      response to the intercalation of Bu4N(+). Hence, this electrochemical method
      offers a versatile procedure to make all graphene sheets in a multi-layered but
      expanded structure accessible for functionalization. On a more general level,
      this approach will provide a versatile way of forming new hybrid materials based
      on intimate bond coupling to graphene via carboxylate groups. 

PMID- 24852931
TI  - Low vacuum annealing of cellulose acetate on nickel towards transparent
      conductive CNT-graphene hybrid films.
AB  - We report a versatile method based on low vacuum annealing of cellulose acetate
      on nickel (Ni) surface for rapid fabrication of graphene and carbon nanotube
      (CNT)-graphene hybrid films with tunable properties. Uniform films mainly
      composed of tri-layer graphene can be achieved via a surface precipitation of
      dissociated carbon at 800  degrees C for 30 seconds under vacuum conditions of
      ~0.6 Pa. The surface precipitation process is further found to be efficient for
      joining the precipitated graphene with pre-coated CNTs on the Ni surface,
      consequently, generating the hybrid films. As expected, the hybrid films exhibit
      substantial opto-electrical and field electron emission properties superior to
      their individual counterparts. The finding suggests a promising route to
      hybridize the graphene with diverse nanomaterials for constructing novel hybrid
      materials with improved performances. 

PMID- 24852932
TI  - Relationship of mismatch repair proteins and survivin in colon polyps and
      carcinomas.
AB  - Mismatch repair genes (MMR) play an essential role in DNA repair. MMR mutations
      predominantly in MLH1, MSH2, MSH6, PMS2, and rarely in PMS1, may cause the
      production of abnormally short or inactivated proteins. The antiapoptotic protein
      survivin functions in the inhibition of apoptosis, regulation of cell division
      and also enhances angiogenesis. Both MMRP and survivin are considered to be
      powerful prognostic parameters. This study was designed to determine the
      relationship between MMRP and survivin in colon lesions. The study included 113
      cases of colon carcinoma and 51 cases of colon polyps. Survivin expression and
      MMRP status were assessed by immunohistochemistry. In each section, expression,
      intensity of immunostaining and percentage of labeled cells were analyzed. In
      carcinomas, immunoreaction was detected in 100/113 cases for MLH1 (88.5%),
      112/113 cases for MSH2 (99.1%), 110/113 cases for MSH6 (97.3%), and 103/113 cases
      for PMS2 (91.2%). Survivin was shown in 47/113 cases (41.6%). The statistical
      analysis confirmed a significant correlation between the expression of MMRP and
      survivin in the assessed parameters. All 51 polyp samples were positive for MLH1,
      MSH2, MSH6 and PMS2. Only 8 of those (15.7%) were positive for survivin.
      Statistically significant differences were observed between the expression of
      MMRP and survivin. In conclusion, this study revealed that MMRP may suppress the
      antiapoptotic function of survivin through p53 inactivation of its promoter in
      grade 1 and grade 2 colon carcinomas. 

PMID- 24852933
TI  - Pediatric emergency care capabilities of Indian Health Service emergency medical
      service agencies serving American Indians/Alaska Natives in rural and frontier
      areas.
AB  - INTRODUCTION: In the USA, the emergency medical services (EMS) system is vital
      for American Indians and Alaska Natives, who are disproportionately burdened by
      injuries and diseases and often live in rural areas geographically far from
      hospitals. In rural areas, where significant health disparities exist, EMS is
      often a primary source of healthcare providing a safety net for uninsured
      individuals or families who otherwise lack access to health-related services. EMS
      is frequently the first entry point for children and their families into the
      healthcare system. The Indian Health Service (IHS) supports the federally funded,
      tribally operated EMS agencies to help meet the affiliated American Indian and
      Alaska Natives' pre-hospital needs. While periodic assessments of state EMS
      agencies capabilities to care for children occur, it appears a systematic
      assessment of IHS EMS agencies in regards to children had not been previously
      conducted. METHODS: A consensus process, involving stakeholders, was used to
      identify topic areas for a survey for assessing the pediatric capabilities of IHS
      EMS. The survey was sent to 75 of 88 IHS EMS agency contacts. RESULTS: Sixty-one
      agencies (81%) responded. Nine agencies (15%) did not have a medical director.
      Agencies without a medical director were less likely to report the availability
      of online (p=0.1) or offline (p<0.01) pediatric medical direction. Half (51%) of
      the agencies had a mass casualties plan; however, 29% reported responding to a
      mass casualty incident, involving a large number of pediatric patients, that
      overwhelmed their service. Most agencies were well integrated with their state
      EMS system with almost all (95%) collecting EMS patient care data and 47% using
      national standard data elements. CONCLUSIONS: In some areas, IHS EMS agencies did
      not have the infrastructure to treat pediatric patients during day-to-day
      operations as well as disasters. Similar to operational challenges faced by rural
      EMS agencies, the IHS agencies lacked a medical director, were unable to provide
      pediatric continuing education, and were overwhelmed during mass casualty
      incidents. Moreover, the overall ratio of IHS EMS to service population is almost
      double that for other EMS agencies. In other areas, agencies were well integrated
      with their state EMS system. One possible solution to increase capabilities to
      care for pediatric patients is combining and sharing of common resources
      including medical directors with their state EMS systems and authorities.

PMID- 24852935
TI  - Statins and contrast-induced acute kidney injury with coronary angiography.
AB  - BACKGROUND: Contrast-induced acute kidney injury is an adverse outcome resulting
      from radiocontrast medium exposure during coronary angiography and percutaneous
      coronary intervention. METHODS: A systematic search was conducted to retrieve
      studies that investigated the impact of statin exposure before coronary
      angiography or percutaneous coronary intervention on the development of contrast
      induced acute kidney injury. The primary outcome was the development of contrast
      induced acute kidney injury. We separately analyzed statin/placebo comparisons
      and high-/low-dose statin comparisons. RESULTS: Fifteen randomized controlled
      trials met inclusion criteria: 11 studies with statin-naive subjects, 2 studies
      with chronic statin users, and 2 studies with unspecified prior statin exposure.
      Statin exposure reduced the risk of contrast-induced acute kidney injury relative
      to placebo (relative risk [RR] 0.63, P = .01) with a nonsignificant reduction in
      the need for hemodialysis (RR 0.25, P = .08). This benefit was also observed in
      high-dose versus low-dose statin trials (RR 0.46, P = .004), in statin-naive
      patients (RR 0.53, P <.0001), and with all studied statins. Higher statin
      exposure reduced contrast-induced acute kidney injury in patients with acute
      coronary syndromes compared with placebo or low-dose statins (RR 0.49, P
      <.00001), with no significant benefit among patients undergoing elective
      procedures (RR 0.86, P = .50). Subgroup analyses confirmed the benefit of statins
      in patients with diabetes, chronic kidney disease, congestive heart failure, and
      those receiving >140 mL of contrast dye. CONCLUSION: Statin therapy is effective
      at reducing the risk of contrast-induced acute kidney injury. It should thus be
      considered, at least on a short-term basis, for patients at increased risk of
      this complication.

PMID- 24852936
TI  - Fine needle aspiration cytology of acinar cell cystadenoma of the pancreas.
AB  - BACKGROUND: Acinar cell cystadenoma (ACC) is a recently recognized cystic lesion
      of the pancreas that demonstrates acinar differentiation and is currently
      believed to behave in a benign fashion. ACC enters the differential diagnosis of
      pancreatic cystic lesions alongside better recognized entities such as mucinous
      cystic and intraductal papillary mucinous neoplasms. Although uncommon, patients
      with ACC can undergo fine needle aspiration (FNA) of the lesion. However, the
      diagnosis is rarely made on cytologic examination due to sparse cellularity.
      Furthermore, the eosinophilic amorphous material in the cyst lumen may be
      mistaken for mucin, resulting in an incorrect diagnosis of a mucinous cyst. To
      date, there is a paucity of literature on the cytomorphology of ACC, both in peer
      reviewed publications and cytopathology texts. CASE: To our knowledge, we present
      the first detailed case report of FNA of ACC in a 22-year-old asymptomatic
      female. The FNA cytology specimen was hypocellular, and the presence of amorphous
      secretions led to the initial diagnosis of a mucinous-type neoplasm. Following
      surgical resection, the cytology specimen was reviewed. CONCLUSION: We discuss
      the cytomorphologic features of ACC along with the potential pitfalls and
      diagnostic implications.

PMID- 24852934
TI  - Pneumococcal vaccine and patients with pulmonary diseases.
AB  - Chronic pulmonary diseases are chronic diseases that affect the airways and lung
      parenchyma. Examples of common chronic pulmonary diseases include asthma,
      bronchiectasis, chronic obstructive lung disease, lung fibrosis, sarcoidosis,
      pulmonary hypertension, and cor pulmonale. Pulmonary infection is considered a
      significant cause of mortality in patients with chronic pulmonary diseases.
      Streptococcus pneumoniae is the leading isolated bacteria from adult patients
      with community-acquired pneumonia, the most common pulmonary infection.
      Vaccination against S. pneumoniae can reduce the risk of mortality, especially
      from more serious infections in both immunocompetent and immunocompromised
      patients. Patients with chronic pulmonary diseases who take steroids or
      immunomodulating therapy (eg, methotrexate, anti-tumor necrosis factor
      inhibitors), or who have concurrent sickle cell disease or other
      hemoglobinopathies, primary immunodeficiency disorders, human immunodeficiency
      virus infection/acquired immunodeficiency syndrome, nephrotic syndrome, and
      hematologic or solid malignancies should be vaccinated with both 13-valent
      pneumococcal conjugate vaccine and the pneumococcal polysaccharide vaccine 23
      valent. 

PMID- 24852937
TI  - Reference values for biochemical parameters in blood serum of young and adult
      alpacas (Vicugna pacos).
AB  - The aim of this study was to establish reference interval for biochemical
      parameters in blood of alpacas on the basis of large population of clinically
      healthy animals, and to determine the influence of sex, age and season on
      nitrogen and lipid metabolites, enzymes, electrolytes, vitamins and minerals in
      blood of alpacas. Blood samples were collected from 311 alpacas (61 males and 201
      females >6 months of age and 49 crias (21 males and 28 females) ?6 months of
      age). Selected farms were located in Central Europe (Czech Republic and Germany).
      We determined 24 biochemical parameters from blood serum. We performed the
      comparison of results by the sex of animals and for the older group also the
      comparison of the results with regard to the season, respectively, to the feeding
      period. We found no highly significant difference (P<0.01) between males and
      females with the exception of gamma-glutamyl transferase (GGT), alkaline
      phosphatase (ALP) and cholesterol. We found 15 significantly different parameters
      between the group of crias 6 months of age and the older alpacas. Based on our
      findings we suggest for most parameters to use different reference intervals
      (especially ALP, cholesterol, total protein, globulin, non-esterified fatty acids
      (NEFA), GGT and phosphorus) for the two above-mentioned age groups. Another
      important finding is the differences between some parameters in older group of
      alpacas in summer/winter feeding period. Animals in the summer feeding period
      have higher values of parameters related to fat mobilization (beta
      hydroxybutyrate, NEFA) and liver metabolism (bilirubin, alanine
      aminotransferase). The winter period with increased feeding of supplements with
      higher amount of fat, vitamins and minerals is characteristic by increased values
      of cholesterol, triglycerides, vitamins A and E, and some minerals (K, Ca, Mg and
      Cl) in blood serum. Clinical laboratory diagnosis of metabolic disturbances may
      be improved with use of age-based reference values and with consideration of
      seasonal differences. 

PMID- 24852938
TI  - Inclusion of Palmaria palmata (red seaweed) in Atlantic salmon diets: effects on
      the quality, shelf-life parameters and sensory properties of fresh and cooked
      salmon fillets.
AB  - BACKGROUND: The use of Palmaria palmata (PP) as a natural ingredient in farmed
      Atlantic salmon diets was investigated. The effect of salmon diet supplementation
      with P. palmata (0, 5, 10 and 15%) or synthetic astaxanthin (positive control,
      PC) for 16 weeks pre-slaughter on quality indices of fresh salmon fillets was
      examined. The susceptibility of salmon fillets/homogenates to oxidative stress
      conditions was also measured. RESULTS: In salmon fillets stored in modified
      atmosphere packs (60% N2 /40% CO2 ) for up to 15 days at 4  degrees C, P. palmata
      increased surface -a* (greenness) and b* (yellowness) values in a dose-dependent
      manner, resulting in a final yellow/orange flesh colour. In general, the dietary
      addition of P. palmata had no effect on pH, lipid oxidation (fresh, cooked and
      fillet homogenates) and microbiological status. 'Eating quality' sensory
      descriptors (texture, odour and oxidation flavour) in cooked salmon fillets were
      not influenced by dietary P. palmata. Salmon fed 5% PP showed increased overall
      acceptability compared with those fed PC and 0% PP. CONCLUSION: Dietary P.
      palmata was ineffective at providing red coloration in salmon fillets, but
      pigment deposition enhanced fillets with a yellow/orange colour. Carotenoids from
      P. palmata may prove to be a natural pigment alternative to canthaxanthin in
      salmon feeds.

PMID- 24852939
TI  - Morphology and histomorphometry of the bladder and urethra in ovariectomized rats
      after long-term use of tibolone.
AB  - BACKGROUND: This study aimed to evaluate the effect of long-term high-dose
      tibolone on the bladders and urethras of ovariectomized rats. METHODS: Bilateral
      ovariectomy was performed in 14 young adult rats randomly divided into 2 groups.
      Experimental rats (n = 9) received 1 mg/day of tibolone orally; control rats (n =
      6) received a placebo. After 150 days, the bladders and urethras were removed.
      Bladder cell proliferation was analyzed by Ki-67 immunohistochemistry. A
      histomorphometric analysis was performed for epithelial thickness and the percent
      areas of collagen fibers and blood vessels. Data were compared using a Mann
      Whitney test (significance level at p < 0.05). RESULTS: Urothelial thickness and
      the percent area of collagen fibers and blood vessels were not significantly
      different between the tibolone and control groups in the bladder and urethra. In
      addition, urothelium cell proliferation in the bladder showed a low
      immunopositivity in both groups. Furthermore, the glycogen and glycoprotein
      contents in urethral epithelium were slightly modified by tibolone and no change
      was observed in the bladder. CONCLUSION: Long-term administration of tibolone has
      no effect on urothelial trophism, collagen fibers, the number of vessels, or cell
      proliferation in the urethra and bladder of the ovariectomized rat.

PMID- 24852940
TI  - Antibody-conjugated paramagnetic nanobeads: kinetics of bead-cell binding.
AB  - Specific labelling of target cell surfaces using antibody-conjugated paramagnetic
      nanobeads is essential for efficient magnetic cell separation. However, studies
      examining parameters determining the kinetics of bead-cell binding are scarce.
      The present study determines the binding rates for specific and unspecific
      binding of 150 nm paramagnetic nanobeads to highly purified target and non-target
      cells. Beads bound to cells were enumerated spectrophotometrically. Results show
      that the initial bead-cell binding rate and saturation levels depend on initial
      bead concentration and fit curves of the form A(1 - exp(-kt)). Unspecific binding
      within conventional experimental time-spans (up to 60 min) was not detectable
      photometrically. For CD3-positive cells, the probability of specific binding was
      found to be around 80 times larger than that of unspecific binding. 

PMID- 24852941
TI  - Insulin-Like Growth Factor I Inhibits Alveolar Bone Loss Following Tooth
      Extraction in Rats.
AB  - BACKGROUND: Alveolar bone is often lost after tooth extraction. Few studies have
      assessed the longitudinal changes in bone volume that occur within these
      extraction sites. PURPOSE: To investigate the longitudinal morphological changes
      in extraction sockets following sustained continuous subcutaneous infusion of
      human recombinant insulin-like growth factor I (IGF-I). MATERIALS AND METHODS:
      Fourteen rats were subjected to right mandibular first molar extraction.
      Experimental rats (n = 7) received a continuous subcutaneous infusion of human
      recombinant IGF-I (320 mg/day) for 3 weeks by osmotic minipump. Control animals
      were treated with saline via the same method (n = 7). All rats were then housed
      for an additional 3 weeks. Micro-CT scanning was performed immediately after
      tooth extraction and at 1, 2, 3, and 6 weeks after extraction. RESULTS: New bone
      formation was markedly higher in the IGF-I-treated group as compared with the
      control group. The loss in alveolar ridge height in the IGF-I group was
      significantly lower than that in the control group at each time point after
      extraction on the buccal side and at 2, 3, and 6 weeks on the lingual side.
      CONCLUSIONS: IGF-I treatment increases the volume of newly formed bone and
      reduces the loss in alveolar ridge height following tooth extraction.

PMID- 24852942
TI  - An invasive vector of zoonotic disease sustained by anthropogenic resources: the
      raccoon dog in northern Europe.
AB  - The raccoon dog (Nyctereutes procyonoides) is an introduced species in Europe
      with a continually expanding range. Since the species is capable of affecting
      local ecosystems and is a vector for a number of severe zoonotic diseases, it is
      important to understand its food habits. Raccoon dog diet was studied in Estonia
      by examining the contents of 223 stomach samples collected during the coldest
      period of the year, August to March, in 2010-2012. The most frequently consumed
      food categories were anthropogenic plants (e.g. cereals, fruits; FO = 56.1%) and
      carrion (e.g. carcasses of artiodactyls and carnivores; FO = 48.4%). Carrion was
      also the only food category that was consumed significantly more frequently by
      raccoon dogs exhibiting symptoms of sarcoptic mange than by uninfected animals.
      Small mammals, which represent intermediate hosts for the zoonotic tapeworm
      Echinococcus multilocularis, were more commonly recorded in samples also
      containing anthropogenic plants than expected by chance. Comparison of raccoon
      dog and red fox (Vulpes vulpes) diet in Estonia revealed higher overlap than
      found elsewhere in Europe, with 'carrion' and 'anthropogenic plants' making up
      the bulk of both species' diet; however, raccoon dogs were more omnivorous than
      red foxes. Our results suggest that while the use of most food categories
      reflects the phenology of natural food sources, 'anthropogenic plants' and
      'carrion' provide an essential resource for raccoon dogs during the coldest
      period of the year, with the latter resource especially important for individuals
      infected with sarcoptic mange. Since both of these food categories and small
      mammals are often found at supplementary feeding sites for wild boar (Sus
      scrofa), this game management practice may facilitate high densities of
      mesocarnivores and promote the spread of some severe zoonotic diseases, including
      alveolar echinococcosis, trichinellosis, rabies and sarcoptic mange. 

PMID- 24852943
TI  - Interactive ion-mediated sap flow regulation in olive and laurel stems:
      physicochemical characteristics of water transport via the pit structure.
AB  - Sap water is distributed and utilized through xylem conduits, which are vascular
      networks of inert pipes important for plant survival. Interestingly, plants can
      actively regulate water transport using ion-mediated responses and adapt to
      environmental changes. However, ionic effects on active water transport in
      vascular plants remain unclear. In this report, the interactive ionic effects on
      sap transport were systematically investigated for the first time by visualizing
      the uptake process of ionic solutions of different ion compositions (K+/Ca2+)
      using synchrotron X-ray and neutron imaging techniques. Ionic solutions with
      lower K+/Ca2+ ratios induced an increased sap flow rate in stems of Olea europaea
      L. and Laurus nobilis L. The different ascent rates of ionic solutions depending
      on K+/Ca2+ ratios at a fixed total concentration increases our understanding of
      ion-responsiveness in plants from a physicochemical standpoint. Based on these
      results, effective structural changes in the pit membrane were observed using
      varying ionic ratios of K+/Ca2+. The formation of electrostatically induced
      hydrodynamic layers and the ion-responsiveness of hydrogel structures based on
      Hofmeister series increase our understanding of the mechanism of ion-mediated sap
      flow control in plants. 

PMID- 24852944
TI  - Antigen-specific culture of memory-like CD8 T cells for adoptive immunotherapy.
AB  - Cytotoxic T cells typically are expanded ex vivo in culture with IL2 for adoptive
      immunotherapy. This culture period leads to a differentiated phenotype and
      acquisition of effector function, as well as a loss of in vivo proliferative
      capability and antitumor efficacy. Here, we report antigen-specific and
      polyclonal expansion of cytotoxic T cells in a cocktail of cytokines and small
      molecules that leads to a memory-like phenotype in mouse and human cells even
      during extended culture, leading to enhanced in vivo expansion and tumor control
      in mice.

PMID- 24852945
TI  - Unacylated ghrelin suppresses ghrelin-induced neuronal activity in the
      hypothalamus and brainstem of male rats [corrected].
AB  - Ghrelin, the endogenous growth hormone secretagogue, has an important role in
      metabolic homeostasis. It exists in two major molecular forms: acylated (AG) and
      unacylated (UAG). Many studies suggest different roles for these two forms of
      ghrelin in energy balance regulation. In the present study, we compared the
      effects of acute intracerebroventricular administration of AG, UAG and their
      combination (AG+UAG) to young adult Wistar rats on food intake and central
      melanocortin system modulation. Although UAG did not affect food intake it
      significantly increased the number of c-Fos positive neurons in the arcuate
      (ARC), paraventricular (PVN) and solitary tract (NTS) nuclei. In contrast, UAG
      suppressed AG-induced neuronal activity in PVN and NTS. Central UAG also
      modulated hypothalamic expression of Mc4r and Bmp8b, which were increased and
      Mc3r, Pomc, Agrp and Ucp2, which were decreased. Finally, UAG, AG and combination
      treatments caused activation of c-Fos in POMC expressing neurons in the arcuate,
      substantiating a physiologic effect of these peptides on the central melanocortin
      system. Together, these results demonstrate that UAG can act directly to increase
      neuronal activity in the hypothalamus and is able to counteract AG-induced
      neuronal activity in the PVN and NTS. UAG also modulates expression of members of
      the melanocortin signaling system in the hypothalamus. In the absence of an
      effect on energy intake, these findings indicate that UAG could affect energy
      homeostasis by modulation of the central melanocortin system. 

PMID- 24852946
TI  - Effect of erythritol and xylitol on dental caries prevention in children.
AB  - OBJECTIVE: The aim of this study was to test the efficacy of long-term, daily
      intake of erythritol and xylitol candy, compared with sorbitol candy, on the
      development of enamel and dentin caries lesions. METHODS: The study was a double
      blind randomized controlled prospective clinical trial. Altogether 485 primary
      school children, first- and second-graders at baseline, from southeastern Estonia
      participated in this 3-year intervention. Each child consumed four erythritol,
      xylitol or sorbitol (control) candies three times per school day. The daily
      intake of polyol was about 7.5 g. The International Caries Detection and
      Assessment System (ICDAS) was used in the clinical examinations by four
      calibrated examiners at baseline and at 12, 24 and 36 months. RESULTS: The annual
      examination analyses and the follow-up analyses confirmed that the number of
      dentin caries teeth and surfaces at 24 months follow-up and surfaces at 36 months
      follow-up was significantly lower in the mixed dentition in the erythritol group
      than in the xylitol or control group. Time of enamel/dentin caries lesions to
      develop and of dentin caries lesions to progress was significantly longer in the
      erythritol group compared to the sorbitol and xylitol groups. Also the increase
      in caries score was lower in the erythritol group than in the other groups.
      CONCLUSIONS: In the follow-up examinations, a lower number of dentin caries teeth
      and surfaces was found in the erythritol group than in the xylitol or control
      groups. Time to the development of caries lesions was longest in the erythritol
      group. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT01062633.

PMID- 24852947
TI  - Endothelin-1 gene polymorphisms influence cerebrospinal fluid endothelin-1 levels
      following aneurysmal subarachnoid hemorrhage.
AB  - Aneurysmal subarachnoid hemorrhage is a type of stroke with high morbidity and
      mortality. Increased endothelin-1 (ET-1) levels have been associated with
      increased risk of cerebral vasospasm, which is associated with increased
      morbidity. The purpose of this study was to investigate the relationships between
      ET-1 genotypes and ET-1 protein levels in cerebrospinal fluid (CSF) measured 72
      hr before angiographic vasospasm measurement in subjects at high risk of cerebral
      vasospasm. Specifically, this study evaluated the differences between variant
      positive and variant negative groups of nine different ET-1 single-nucleotide
      polymorphisms (SNPs) in relationship with the ET-1 protein exposure rate. The CSF
      ET-1 protein levels were quantified using enzyme-linked immunosorbent assay. One
      functional SNP and eight ET-1 tagging SNPs were selected because they represent
      genetic variability in the entire ET-1 gene. The variant negative group of SNP
      rs2070699 was associated with a significantly higher ET-1 exposure rate than the
      variant positive group (p = 0.004), while the variant positive group of the
      rs5370 group showed a trend toward association with a higher ET-1 exposure rate
      (p = 0.051). Other SNPs were not informative. This is the first study to show
      differences in ET-1 exposure rate 72 hr before angiography in relation to ET-1
      genotypes. These exploratory findings need to be replicated in a larger study; if
      replicated, these differences in genotypes may be a way to inform clinicians of
      those patients at a higher risk of increased ET-1 protein levels, which may lead
      to a higher risk of angiographic vasospasm. 

PMID- 24852948
TI  - Green tea polyphenol epigallocatechin-3-gallate inhibits TNF-alpha-induced
      production of monocyte chemoattractant protein-1 in human umbilical vein
      endothelial cells.
AB  - AIMS: Epigallocatechin-3-gallate (EGCG), a major catechin found in green tea,
      displays a variety of pharmacological properties and recently received attention
      as a prospective dietary intervention in cardiovascular diseases (CVD). This
      study was conducted to test the hypothesis that EGCG was able to inhibit tumor
      necrosis factor-alpha (TNF-alpha)-induced production of monocyte chemoattractant
      protein-1 (MCP-1) in human umbilical vein endothelial cells (HUVECs) and
      investigated the underlying molecular mechanisms. METHODS: The inhibitory effect
      of EGCG on TNF-alpha-induced expression of MCP-1 was measured using ELISA and RT
      qPCR. The effect of EGCG on TNF-alpha-induced nuclear factor-kappa B (NF-kappaB)
      activation was investigated by western blot and luciferase assays. Monocyte
      adhesion assay was detected by microscope. RESULTS: EGCG significantly suppressed
      the TNF-alpha-induced protein and mRNA expression of MCP-1. Investigation of the
      mechanism suggested that EGCG suppressed the TNF-alpha-mediated NF-kappaB
      activation. In addition, the 67-kD laminin receptor (67LR) was involved in EGCG
      mediated suppression of MCP-1 generation. Furthermore, EGCG potently inhibited
      monocyte adhesion to activated HUVECs. CONCLUSION: EGCG suppresses TNF-alpha
      induced MCP-1 expression in HUVECs. This effect was mediated by 67LR and was via
      the inhibition of NF-kappaB activation. Our results demonstrated that EGCG might
      be a possible medicine for CVD prevention and treatment.

PMID- 24852949
TI  - Bilateral agenesis of arcuate fasciculus demonstrated by fiber tractography in
      congenital bilateral perisylvian syndrome.
AB  - Congenital bilateral perisylvian syndrome (CBPS) is a type of cortical
      developmental abnormality associated with distinctive clinical and imaging
      features. Clinical spectrum of this syndrome is quite heterogeneous, with
      different degrees of neurological impairment in affected individuals. High
      definition magnetic resonance imaging (MRI) has a great importance in revealing
      the presence of CBPS, but is limited in elucidating the heterogeneous clinical
      spectrum. The arcuate fasciculus (AF) is a prominent language tract in the
      perisylvian region interconnecting Broca and Wernicke areas, and has a high
      probability of being affected developmentally in CBPS. Herein, we report a case
      of CBPS with investigation of AF using diffusion tensor imaging (DTI) and fiber
      tractography in relation to clinical findings. We postulated that proven absence
      of AF on DTI and fiber tractography would correlate with a severe phenotype of
      CBPS. 

PMID- 24852951
TI  - Humidity-triggered self-healing films with excellent oxygen barrier performance.
AB  - Hybrid films were fabricated via layer-by-layer assembly of layered double
      hydroxide (LDH) nanoplatelets and poly(sodium styrene-4-sulfonate) (PSS) followed
      by subsequent permeation of poly(vinyl alcohol) (PVA), which show excellent
      oxygen barrier performance with humidity-triggered self-healing capability. 

PMID- 24852950
TI  - Comparative clinical pharmacokinetics of antibody-drug conjugates in first-in
      human Phase 1 studies.
AB  - Although there are currently more than 30 antibody-drug conjugates (ADC) in
      clinical development for the treatment of blood cancers and solid tumors,
      comparison of their clinical pharmacokinetics (PK) is challenging because of the
      large number of, and differences between, the targets, ADC constructs, dosing
      regimens, and patient populations. In this review, we standardized the
      evaluation, using non-compartmental PK data reported at Cycle 1, i.e., following
      the first drug administration of what is usually a repeated-dose treatment, in
      monotherapy. We report ADC clinical PK properties, dosing regimen, determination
      of doses ranges and associated maximum tolerated doses. We also evaluated the
      effect of structural characteristics and target types (hematological vs. solid
      tumors) on PK. In addition, we discuss how integration of PK/pharmacodynamics
      approaches on top of classical dose escalation in first-in-human studies may
      improve dosing regimen determination for subsequent phases of clinical
      development. 

PMID- 24852953
TI  - Controlling Salmonella along the food chain in the European Union - progress over
      the last ten years.

PMID- 24852952
TI  - Offering the opportunity for family to be present during cardiopulmonary
      resuscitation: 1-year assessment.
AB  - PURPOSE: To evaluate the psychological consequences among family members given
      the option to be present during the CPR of a relative, compared with those not
      routinely offered the option. METHODS: Prospective, cluster-randomized,
      controlled trial involving 15 prehospital emergency medical services units in
      France, comparing systematic offer for a relative to witness CPR with the
      traditional practice among 570 family members. Main outcome measure was 1-year
      assessment included proportion suffering post-traumatic stress disorder (PTSD),
      anxiety and depression symptoms, and/or complicated grief. RESULTS: Among the 570
      family members [intention to treat (ITT) population], 408 (72%) were evaluated at
      1 year. In the ITT population (N = 570), family members had PTSD-related symptoms
      significantly more frequently in the control group than in the intervention group
      [adjusted odds ratio, 1.8; 95% confidence interval (CI) 1.1-3.0; P = 0.02] as did
      family members to whom physicians did not propose witnessing CPR [adjusted odds
      ratio, 1.7; 95% CI 1.1-2.6; P = 0.02]. In the observed cases population (N =
      408), the proportion of family members experiencing a major depressive episode
      was significantly higher in the control group (31 vs. 23%; P = 0.02) and among
      family members to whom physicians did not propose the opportunity to witness CPR
      (31 vs. 24%; P = 0.03). The presence of complicated grief was significantly
      greater in the control group (36 vs. 21%; P = 0.005) and among family members to
      whom physicians did not propose the opportunity to witness resuscitation (37 vs.
      23%; P = 0.003). CONCLUSIONS: At 1 year after the event, psychological benefits
      persist for those family members offered the possibility to witness the CPR of a
      relative in cardiac arrest.

PMID- 24852954
TI  - Multidisciplinary investigation of a multicountry outbreak of Salmonella Stanley
      infections associated with turkey meat in the European Union, August 2011 to
      January 2013.
AB  - Between August 2011 and January 2013, an outbreak of Salmonella enterica serovar
      Stanley (S. Stanley) infections affected 10 European Union (EU) countries, with a
      total of 710 cases recorded. Following an urgent inquiry in the Epidemic
      Intelligence Information System for food- and waterborne diseases (EPIS-FWD) on
      29 June 2012, an international investigation was initiated including EU and
      national agencies for public health, veterinary health and food safety. Two of
      three local outbreak investigations undertaken by affected countries in 2012
      identified turkey meat as a vehicle of infection. Furthermore, routine EU
      monitoring of animal sources showed that over 95% (n=298) of the 311 S. Stanley
      isolates reported from animal sampling in 2011 originated from the turkey food
      production chain. In 2004-10, none had this origin. Pulsed-field gel
      electrophoresis (PFGE) profile analysis of outbreak isolates and historical S.
      Stanley human isolates revealed that the outbreak isolates had a novel PFGE
      profile that emerged in Europe in 2011. An indistinguishable PFGE profile was
      identified in 346 of 464 human, food, feed, environmental and animal isolates
      from 16 EU countries: 102 of 112 non-human isolates tested were from the turkey
      production chain. On the basis of epidemiological and microbiological evidence,
      turkey meat was considered the primary source of human infection, following
      contamination early in the animal production chain.

PMID- 24852955
TI  - Investigating an outbreak of Clostridium perfringens gastroenteritis in a school
      using smartphone technology, London, March 2013.
AB  - On 22 March 2013, 150 of 1,255 students (13-17 years) and staff at a school in
      London reported gastrointestinal symptoms; onset peaked 8 to 12 hours after a
      lunch served in the school on 21 March. We performed a retrospective cohort study
      of all students and staff. We defined cases as school attenders on 20 and 21
      March with onset of gastrointestinal symptoms between 20 and 23 March. We tested
      food, environmental and stool samples of cases for common pathogens and bacterial
      toxins. We administered an online questionnaire via email, encouraging the use of
      smartphones to respond, to measure risk of illness for food items eaten at school
      on 20 and 21 March. Survey response was 45%. Adjusted risk ratios were generated
      in a multivariable analysis. Those who ate chicken balti on 21 March were 19.3
      times more likely to become ill (95% confidence interval: 7.3-50.9). Clostridium
      perfringens was detected in all 19 stool samples collected. Within eight school
      hours of its launch, 412 of 561 (73%) responders had completed the survey.
      Hygienic standards in the kitchen were satisfactory. The investigation was done
      rapidly due to smartphone technology and we recommend considering this technology
      in future outbreaks.

PMID- 24852956
TI  - Long-term control of carbapenemase-producing Enterobacteriaceae at the scale of a
      large French multihospital institution: a nine-year experience, France, 2004 to
      2012.
AB  - In 2009, following the occurrence of several outbreaks of carbapenemase-producing
      Enterobacteriaceae (CPE), a programme for controlling the spread of CPE was
      implemented in the 38 hospitals of the Assistance Publique-Hopitaux de Paris, a
      21,000-bed institution. This programme included recommendations to isolate, and
      screen for CPE, patients previously hospitalised abroad, and bundled measures to
      control cross transmission (barrier precautions, dedicated staff and screening of
      contact patients). From 2004 to 2012, 140 CPE index cases were identified, 17
      leading to outbreaks. After application of the programme, in spite of an increase
      in the number of CPE index cases epidemiologically linked with a recent stay or
      hospitalisation abroad, the proportion of cases followed by outbreaks, which was
      40% (4/10) before 2009, decreased to 10% (13/130) (p=0.02), and the proportion of
      secondary cases among all CPE cases decreased from 69% (22/32) to 23% (38/168),
      (p<0.001). The number of secondary cases varied significantly depending on the
      speed and strength of the measures implemented around the CPE index case: quick
      (within two days of patient admission at the hospital) setting of nursing staff
      dedicated to the patient, quick setting of simple barrier precautions, or delayed
      measures of control (p=0.001). A sustained and coordinated strategy can lead to
      control CPE at the level of a large regional multi-hospital institution in a
      country where CPE are at an emerging stage.

PMID- 24852957
TI  - Letter to the editor: measles on the cruise ship: links with virus spreading into
      an emergency department in Southern Italy.

PMID- 24852958
TI  - Authors reply: measles on the cruise ship: links with virus spreading into an
      emergency department in Southern Italy.

PMID- 24852959
TI  - Effect of wire size on maxillary arch force/couple systems for a simulated high
      canine malocclusion.
AB  - AIMS: To better understand the effects of copper nickel titanium (CuNiTi)
      archwire size on bracket-archwire mechanics through the analysis of force/couple
      distributions along the maxillary arch. The hypothesis is that wire size is
      linearly related to the forces and moments produced along the arch. MATERIALS AND
      METHODS: An Orthodontic Simulator was utilized to study a simplified high canine
      malocclusion. Force/couple distributions produced by passive and elastic ligation
      using two wire sizes (Damon 0.014 and 0.018 inch) measured with a sample size of
      144. RESULTS: The distribution and variation in force/couple loading around the
      arch is a complicated function of wire size. The use of a thicker wire increases
      the force/couple magnitudes regardless of ligation method. Owing to the non
      linear material behaviour of CuNiTi, this increase is less than would occur based
      on linear theory as would apply for stainless steel wires. CONCLUSIONS: The
      results demonstrate that an increase in wire size does not result in a
      proportional increase of applied force/moment. This discrepancy is explained in
      terms of the non-linear properties of CuNiTi wires. This non-proportional force
      response in relation to increased wire size warrants careful consideration when
      selecting wires in a clinical setting.

PMID- 24852960
TI  - Spatio-temporal factors associated with meningococcal meningitis annual incidence
      at the health centre level in Niger, 2004-2010.
AB  - BACKGROUND: Epidemics of meningococcal meningitis (MM) recurrently strike the
      African Meningitis Belt. This study aimed at investigating factors, still poorly
      understood, that influence annual incidence of MM serogroup A, the main etiologic
      agent over 2004-2010, at a fine spatial scale in Niger. METHODOLOGY/PRINCIPAL
      FINDINGS: To take into account data dependencies over space and time and control
      for unobserved confounding factors, we developed an explanatory Bayesian
      hierarchical model over 2004-2010 at the health centre catchment area (HCCA)
      level. The multivariate model revealed that both climatic and non-climatic
      factors were important for explaining spatio-temporal variations in incidence:
      mean relative humidity during November-June over the study region (posterior mean
      Incidence Rate Ratio (IRR) = 0.656, 95% Credible Interval (CI) 0.405-0.949) and
      occurrence of early rains in March in a HCCA (IRR = 0.353, 95% CI 0.239-0.502)
      were protective factors; a higher risk was associated with the percentage of
      neighbouring HCCAs having at least one MM A case during the same year (IRR =
      2.365, 95% CI 2.078-2.695), the presence of a road crossing the HCCA (IRR =
      1.743, 95% CI 1.173-2.474) and the occurrence of cases before 31 December in a
      HCCA (IRR = 6.801, 95% CI 4.004-10.910). At the study region level, higher annual
      incidence correlated with greater geographic spread and, to a lesser extent, with
      higher intensity of localized outbreaks. CONCLUSIONS: Based on these findings, we
      hypothesize that spatio-temporal variability of MM A incidence between years and
      HCCAs result from variations in the intensity or duration of the dry season
      climatic effects on disease risk, and is further impacted by factors of spatial
      contacts, representing facilitated pathogen transmission. Additional unexplained
      factors may contribute to the observed incidence patterns and should be further
      investigated.

PMID- 24852963
TI  - Human beans.

PMID- 24852962
TI  - Engineered glycated amino dendritic polymers as specific nonviral gene delivery
      vectors targeting the receptor for advanced glycation end products.
AB  - The receptor for advanced glycation end products (RAGE) is involved in diabetes
      or angiogenesis in tumors. Under pathological conditions, RAGE is overexpressed
      and upon ligand binding and internalization stimulates signaling pathways that
      promote cell proliferation. In this work, amino dendritic polymers PEI 25 kDa and
      alkylated derivatives of PAMAM-G2 were engineered by the nonenzymatic Maillard
      glycation reaction to generate novel AGE-containing gene delivery vectors
      targeting the RAGE. The glycated dendritic polymers were easily prepared and
      retained the capability to bind and protect DNA from endonucleases. Furthermore,
      while glycation decreased the transfection efficiency of the dendriplexes in CHO
      k1 cells which do not express RAGE, glycated dendriplexes acted as efficient
      transfection reagents in CHO-k1 cells which stably express recombinant RAGE. In
      addition, preincubation with BSA-AGEs, a natural ligand of the RAGE, or dansyl
      cadaverine, an inhibitor of the RAGE internalization, blocked transfection,
      confirming their specificity toward RAGE. The results were confirmed in NRK and
      RAW264.7 cell lines, which naturally express the receptor. The glycated compounds
      retain their transfection efficiency in the presence of serum and promote in vivo
      transfection in a mouse model. Accordingly, RAGE is a suitable molecular target
      for the development of site-directed engineered glycated nonviral gene vectors. 

PMID- 24852961
TI  - Inhibiting sperm pyruvate dehydrogenase complex and its E3 subunit,
      dihydrolipoamide dehydrogenase affects fertilization in Syrian hamsters.
AB  - BACKGROUND/AIMS: The importance of sperm capacitation for mammalian fertilization
      has been confirmed in the present study via sperm metabolism. Involvement of the
      metabolic enzymes pyruvate dehydrogenase complex (PDHc) and its E3 subunit,
      dihydrolipoamide dehydrogenase (DLD) in hamster in vitro fertilization (IVF) via
      in vitro sperm capacitation is being proposed through regulation of sperm
      intracellular lactate, pH and calcium. METHODOLOGY AND PRINCIPAL FINDINGS:
      Capacitated hamster spermatozoa were allowed to fertilize hamster oocytes in
      vitro which were then assessed for fertilization, microscopically. PDHc/DLD was
      inhibited by the use of the specific DLD-inhibitor, MICA (5-methoxyindole-2
      carboxylic acid). Oocytes fertilized with MICA-treated (MT) [and thus PDHc/DLD
      inhibited] spermatozoa showed defective fertilization where 2nd polar body
      release and pronuclei formation were not observed. Defective fertilization was
      attributable to capacitation failure owing to high lactate and low intracellular
      pH and calcium in MT-spermatozoa during capacitation. Moreover, this defect could
      be overcome by alkalinizing spermatozoa, before fertilization. Increasing
      intracellular calcium in spermatozoa pre-IVF and in defectively-fertilized
      oocytes, post-fertilization rescued the arrest seen, suggesting the role of
      intracellular calcium from either of the gametes in fertilization. Parallel
      experiments carried out with control spermatozoa capacitated in medium with low
      extracellular pH or high lactate substantiated the necessity of optimal sperm
      intracellular lactate levels, intracellular pH and calcium during sperm
      capacitation, for proper fertilization. CONCLUSIONS: This study confirms the
      importance of pyruvate/lactate metabolism in capacitating spermatozoa for
      successful fertilization, besides revealing for the first time the importance of
      sperm PDHc/ DLD in fertilization, via the modulation of sperm intracellular
      lactate, pH and calcium during capacitation. In addition, the observations made
      in the IVF studies in hamsters suggest that capacitation failures could be a
      plausible cause of unsuccessful fertilization encountered during human assisted
      reproductive technologies, like IVF and ICSI. Our studies indicate a role of
      sperm capacitation in the post-penetration events during fertilization.

PMID- 24852964
TI  - Oral surgery: Prominent bone shelves.

PMID- 24852965
TI  - Dental graduates: Not all doom and gloom.

PMID- 24852966
TI  - Bolitho not Bolam.

PMID- 24852967
TI  - Erosive lichen planus.

PMID- 24852969
TI  - Feature: What is your Plan B?

PMID- 24852970
TI  - Support the campaign against DFT salary cut.

PMID- 24852971
TI  - High risk kids should brush with more fluoride.

PMID- 24852972
TI  - William David Stalley.

PMID- 24852973
TI  - A dentist's life: I always try to see the good in a situation.

PMID- 24852976
TI  - Apply for NICE accreditation.

PMID- 24852980
TI  - Dental centre opens in converted Yorkshire mansion.

PMID- 24852982
TI  - Exeter funds portable dental surgery.

PMID- 24852984
TI  - Phillip Cannell: 'A successful practice depends on its people'.
AB  - Phillip Cannell is a partner at Chalkwell Dental Practice in Southend and a
      senior lecturer at the University of Essex. His research interests include the
      use of skill mix within primary care dentistry, clinical audit and work-based
      education. 

PMID- 24852985
TI  - Craniofacial dystrophy. A possible syndrome?
AB  - This article proposes a possible syndrome, craniofacial dystrophy (CFD), as one
      of the underlying causes of malocclusion and a range of other symptoms. These
      symptoms have seen a dramatic rise in the twentieth century, lack a clear
      aetiology and are currently treated symptomatically. Over the last 10,000 years
      there has been a progressive downswing in the anterior craniofacial structure
      (ACS), possibly due to a combination of changes in the masticatory effort and the
      posture of the tongue and the mandible. If the mouth is postured open and the
      muscles are weaker the face lengthens, a downswing, reducing the cross sectional
      area at the level of the oropharynx. This leads to less space for the tongue, the
      airway and the teeth, and is exacerbated by an increasingly evident 'suckling
      like' swallowing pattern. Changes in the shape of the ACS affect the functions
      for which this structure is responsible, leading to a range of symptoms,
      including malocclusion. Certain compensatory responses are possible to maintain
      these functions, primarily the airway. These vary between individuals, may be
      under genetic influence and may also influence the ACS and dentition, at times
      creating vicious cycles.

PMID- 24852987
TI  - Clinical guide to periodontology: part 3. Multidisciplinary integrated treatment.
AB  - The establishment of periodontal health should be a primary aim in all treatment
      plans. The methods by which this can be achieved have been dealt with in previous
      chapters, but there are a number of situations where integration of these
      treatment methods with other dental disciplines needs to be clarified. To
      simplify matters this chapter will consider periodontal implications in three
      main areas: treatment of drifted anterior teeth, pre-restorative procedures and
      replacement of missing teeth. 

PMID- 24852986
TI  - Minimal intervention dentistry II: part 7. Minimal intervention in cariology: the
      role of glass-ionomer cements in the preservation of tooth structures against
      caries.
AB  - Glass-ionomer cements (GICs) are essential materials in clinical practice because
      of their versatility, self-adhesion to enamel and dentine, and good
      biocompatibility. In addition, being chemically cured, with no shrinkage stress,
      makes them well suited for minimally invasive restorative techniques. This
      article looks at some of the clinical situations where the chemical adhesion and
      high biocompatibility of GIC are important for clinical success: excavation of
      deep carious lesions, fissure sealing and protection of root surfaces against
      caries.

PMID- 24852988
TI  - Skin cancer - an overview for dentists.
AB  - Skin cancer is common and an increasing problem in the UK. It frequently occurs
      on the head and neck skin. A significant proportion of the adult population in
      the UK visits the dentist each year, thus making dental practitioners ideally
      placed to identify suspicious lesions, which could be skin cancer, as part of
      their routine extra-oral examination. These patients can then be referred on to
      hospital or their GP for further management. The dentist can also give advice on
      risk factors and self-monitoring to patients. This paper aims to describe the
      risk factors, pathology, presentation and treatments for the three most common
      forms of skin cancer - basal and squamous cell carcinomas, and malignant
      melanoma, to give the dental practitioner the knowledge and confidence to examine
      for and identify these skin cancers. 

PMID- 24852993
TI  - Summary of: The quality of orthodontic practice websites.

PMID- 24852994
TI  - Summary of: Apical periodontitis and the technical quality of root canal
      treatment in an adult sub-population in London.

PMID- 24852995
TI  - Trends and costs of high concentration fluoride toothpaste prescribing in
      Scotland.
AB  - Within Scotland there has been a significant increase in the prescription of
      2,800 ppm and 5,000 ppm fluoride toothpaste. The objective of this paper was to
      analyse the trends in high concentration fluoride toothpaste (HCFT) in the five
      Scottish South East and Tayside (SEAT) health boards and consider the options for
      future national management of this prescribing. A retrospective analysis of
      routine prescribing data for the years 2006-2012 was carried out in primary care
      dental practices in Scotland. The cost of HCFT prescribing in the five Scottish
      health boards has increased from L15,243 (4,147 items) in 2006/07 to L206,529
      (24,113 items), in 2011/12. Out of 2,430 dental list numbers, 100 list numbers
      (4.1%) accounted for 70% of the total prescribing costs (L144,367). The public
      dental service employs 153 (6%) of dentists working in Scotland, who in turn
      prescribe 11.6% HCFT. There is a need to ensure that the prescription of HCFT is
      both encouraged as best practice care but also managed appropriately to ensure
      that its delivery is targeted at those who are most in need.

PMID- 24852996
TI  - The relevance of NICE to dentistry - what can it do for me?
AB  - Elizabeth Robb, a senior special care dentist, was awarded a NICE Fellowship in
      2012, a first for the profession. The NICE website is a goldmine of information
      for all healthcare professionals including dentists and dental care
      professionals. This article looks at some of the most useful parts of the website
      and explains the everyday relevance of NICE to all branches of the profession
      from the dental student to the coalface clinician and the academic researcher. 

PMID- 24853010
TI  - The quality of orthodontic practice websites.
AB  - OBJECTIVE: To evaluate orthodontic practice websites for the reliability of
      information presented, accessibility, usability for patients and compliance to
      General Dental Council (GDC) regulations on ethical advertising. SETTING: World
      Wide Web. MATERIALS AND METHODS: The term 'orthodontic practice' was entered into
      three separate search engines. The 30 websites from the UK were selected and
      graded according to the LIDA tool (a validated method of evaluating healthcare
      websites) for accessibility, usability of the website and reliability of
      information on orthodontic treatment. The websites were then evaluated against
      the GDC's Principles for ethical advertising in nine different criteria. RESULTS:
      On average, each website fulfilled six out of nine points of the GDC's criteria,
      with inclusion of a complaints policy being the most poorly fulfilled criteria.
      The mean LIDA score (a combination of usability, reliability and accessibility)
      was 102/144 (standard deviation 8.38). The websites scored most poorly on
      reliability (average 43% SD 11.7), with no single website reporting a clear,
      reliable method of content production. Average accessibility was 81% and
      usability 73%. CONCLUSIONS: In general, websites did not comply with GDC
      guidelines on ethical advertising. Furthermore, practitioners should consider
      reporting their method of information production, particularly when making claims
      about efficiency and speed of treatment in order to improve reliability.

PMID- 24853012
TI  - The chance of small interfering RNAs as eligible candidates for a personalized
      treatment of prostate cancer.
AB  - BACKGROUND: Prostate cancer is one of the leading malignant tumors in men.
      Current therapies are associated with severe side effects making it problematic
      for many multi-morbid patients to receive treatment. Prostate specific antigen,
      serum response factor (SRF), signal transducer and activator of transcription-3
      (STAT3), hypoxia-inducible factor-1alpha (HIF-1alpha), HIF-2alpha, E2F1 and
      Survivin are well known proteins being overexpressed in cancer cells, expediting
      cell growth and also demonstrated in prostate cancer cells. Targeting these genes
      using the RNA-Interference pathway could be a new approach for prostate cancer
      therapy with fewer side effects. METHODS: Three prostate cancer cell lines were
      cultured under standard conditions and transfected with three different
      concentrations (25 nM, 50 nM, 100 nM) of specific small interfering RNAs (siRNAs)
      targeting SRF, STAT3, HIF1alpha, HIF2alpha, E2F1 and Survivin in a non-viral
      manner. Cells treated with non-specific siRNA (SCR-siRNA) served as control.
      Changes of messenger RNA (mRNA) levels were determined using quantitative real
      time polymerase chain reaction (qRT-PCR). The analysis of the effect of siRNA on
      the number of cells was detected using CASY cell counter system. RESULTS:
      Transfections of the PC-3 cell line with specific siRNA especially against
      Survivin, E2F1, HIF1alpha- and HIF2alpha-siRNA resulted in a significant
      reduction of intracellular mRNA concentration together with a significant
      decreased number of cells. In the LnCAP and DU-145 cell lines Survivin and E2F1
      showed similar effects. The impact of silencing STAT3 or SRF showed little
      influence on the amount of cells in all three cell lines. CONCLUSIONS: This study
      shows that RNAi succeeds in silencing gene expression and reducing the number of
      cells in differing dimensions depending on the transfected cell line and used
      siRNA.

PMID- 24853013
TI  - Ten lessons from EGFR.

PMID- 24853011
TI  - Apical periodontitis and the technical quality of root canal treatment in an
      adult sub-population in London.
AB  - AIM: To assess the prevalence of apical periodontitis (AP) and the technical
      quality of root canal treatment in an adult sub-population in London.
      METHODOLOGY: Panoramic radiographs of 136 patients who attended a dental hospital
      were collected. The periapical health of teeth present was assessed
      radiographically and the presence or absence of AP noted. The technical quality
      of the root canal treatment was scored as adequate or inadequate, based on the
      European Society of Endodontology (2006) guidelines. RESULTS: A total of 3,396
      teeth were assessed; AP was detected in 4.1% of the teeth. Forty-nine percent of
      patients had at least one tooth with radiographic evidence of AP. The percentage
      of root filled teeth with AP was 38.3%. AP was significantly more frequently
      found in root treated, compared with non-root treated, teeth (p <0.001). In 44.3%
      of the cases, the technical quality of the root canal filling was inadequate. AP
      was detected in 14% of adequately, compared with 68.6% of inadequately, root
      filled teeth. There is a significant negative correlation between the technical
      quality of root canal treatment and the presence of AP (p <0.001). CONCLUSIONS:
      There was a high prevalence of AP and poor technical quality root canal
      treatment; a strong association between AP and root filled teeth, and between the
      periapical health and the technical quality of the root canal treatment. The
      results are consistent with previous studies using similar methodology and re
      confirmed that high technical quality root canal treatment is crucial to ensure a
      favourable treatment outcome.

PMID- 24853014
TI  - Prospective analysis of efficacy and safety of an individualized-midazolam-dosing
      protocol for sedation during prolonged bronchoscopy.
AB  - BACKGROUND: Newer more advanced techniques in bronchoscopy may require longer
      procedure times, although a standard protocol for sedation during prolonged
      bronchoscopy has not yet been defined. METHODS: We designed a prospective, non
      randomized, single-arm study (UMIN trial number 000003971) using patient
      questionnaires and vital sign monitoring to assess the efficacy and safety of a
      standardized midazolam dosing protocol based on gender and age for use during
      bronchoscopy. The loading dose of midazolam was 0.075mg/kg for men <=65 years old
      and women <=70 and 0.05mg/kg for men >=66 years and women >=71 years, with
      subsequent doses of one-half the loading dose to be administered every 20min. The
      primary endpoint was tolerability and secondary endpoints included anxiety and
      recall of procedure, willingness to undergo repeat procedure, and complications.
      Safety was evaluated in terms of monitored changes in blood pressures, ECG,
      oxygen saturation, and CO2 content in expiration during the procedure. RESULTS: A
      total of 204 patients were included in the study. Overall, 163 patients (79.9%)
      reported "no distress" during the procedure, 185 patients (90.7%) reported "no
      anxiety," and 175 (85.8%) replied that they would accept a repeat procedure, if
      necessary. The mean minimum oxygen saturation was 90.2% and the mean maximum
      expiratory CO2 level was 37.7mmHg. There were no serious complications related to
      the protocol. CONCLUSIONS: The midazolam dosing protocol examined in this study
      was safe and effective. It is simple, and it could easily be translated to
      routine clinical practice.

PMID- 24853015
TI  - Pulmonary nocardiosis: a clinical analysis of 59 cases.
AB  - BACKGROUND: Pulmonary nocardiosis is a rare but severe infection caused by
      Nocardia species. This study aimed at describing the clinical characteristics and
      prognosis of pulmonary nocardiosis. METHODS: An observational, retrospective
      study was undertaken of patients diagnosed with pulmonary nocardiosis over a 13
      year period at the Kinki-Chuo Chest Medical Center, Osaka, Japan. RESULTS: Seven
      patients with airway nocardial colonization and 59 patients with pulmonary
      nocardiosis were identified, one of whom had disseminated nocardiosis. Patients
      with pulmonary nocardiosis were predominantly male patients (73%), with a mean
      age of 66 (range, 15-88) years. New-onset cough and dyspnea were the most common
      manifestations (76%). Although 52 (88%) patients had at least one underlying
      pulmonary disease, most patients did not appear to be systemically
      immunocompromised. The predominant abnormality on chest computed tomography in
      pulmonary nocardiosis was airspace consolidation (52%), sometimes associated with
      cavitation. Multivariate Cox proportional-hazards analysis revealed the following
      significant and independent risk factors for overall mortality: age >68 years
      (hazard ratio [HR], 4.7; 95% confidence interval [CI], 1.6-14; p=0.05), pulmonary
      aspergillosis (HR, 8.8; 95% CI, 2.4-33; p=0.01), and
      trimethoprim/sulfamethoxazole (TMP-SMZ) resistance (HR, 4.3; 95% CI, 1.6-11;
      p=0.04). CONCLUSIONS: Clinicians should be aware that pulmonary nocardiosis can
      occur even in immunocompetent patients, especially those with an underlying
      pulmonary disease. In pulmonary nocardiosis, older age, pulmonary aspergillosis,
      and TMP-SMZ resistance are associated with increased risk of mortality.

PMID- 24853016
TI  - Current trends in the management of pulmonary hypertension associated with
      respiratory disease in institutions approved by the Japanese Respiratory Society.
AB  - BACKGROUND: Pulmonary hypertension (PH) often correlates with respiratory disease
      severity. Right heart catheterization (RHC) is recommended for the definitive
      diagnosis of PH associated with respiratory disease (R-PH). However, no previous
      studies have evaluated the perceived necessity for pulmonologists to use RHC for
      R-PH diagnosis, or the management of R-PH in Japan. METHODS: Questionnaires were
      mailed to 855 institutions, approved by the Japanese Respiratory Society.
      Questions included the prevalence and necessity of RHC and other methods in R-PH
      diagnosis, and current trends in the treatment of R-PH. RESULTS: Questionnaires
      were returned from 289 institutions (34%). Patients with R-PH were examined by
      pulmonologists in 89% of institutions; some pulmonologists performed
      echocardiography (15%) and some RHC (13%). Echocardiography was used to diagnose
      R-PH in 99% of institutions and RHC was used in 36%. RHC was considered in cases
      of suspected PH in 49% of institutions and prior to initiation of pulmonary
      arterial hypertension (PAH)-specific therapy in 57%. Of patients diagnosed with R
      PH, 47% were treated with ambulatory oxygen therapy. Furthermore, 98 of 145
      institutions used PAH-specific therapy to treat R-PH. Of the 1355 patients who
      underwent RHC as a part of PH evaluation, 29% were confirmed to have PH, and 8%
      had severe PH with a mean pulmonary arterial pressure of >=35mmHg. CONCLUSIONS:
      The current diagnostic and treatment modalities for R-PH in Japan were evaluated.
      Although few pulmonologists perform RHC for R-PH diagnosis in Japan, more than
      half consider using RHC for patients before initiating PAH-specific therapy.

PMID- 24853017
TI  - Endobronchial ultrasound-guided transbronchial needle aspiration in the diagnosis
      of small cell lung cancer.
AB  - BACKGROUND: Massive lymphadenopathy and direct mediastinal invasion are well
      recognized phenomena in patients with small cell lung cancer (SCLC). The aim of
      this study was to assess the utility of endobronchial ultrasound-guided
      transbronchial needle aspiration (EBUS-TBNA) in the diagnosis of SCLC. METHODS:
      We retrospectively reviewed the records of 780 patients who underwent EBUS-TBNA
      at our institution from March 2004 to June 2012. Of these, 101 had a final
      diagnosis of SCLC. Excluding 3 patients with known SCLC who underwent EBUS-TBNA
      for staging purposes and including 2 patients who underwent EBUS-TBNA twice for
      the diagnosis of recurrence after achieving complete response by chemoradiation
      therapy during the study period, a total of 100 EBUS-TBNA procedures in 98
      patients were analyzed. RESULTS: Other diagnostic tests prior to the initial EBUS
      TBNA had failed to yield a diagnosis in 41 patients. The overall diagnostic yield
      of EBUS-TBNA for SCLC was 97% (97 of 100). Rapid on-site cytologic evaluation
      (ROSE) was performed at the operator's discretion in 77 procedures. ROSE did not
      have any impact on diagnostic yield (99% with ROSE vs. 90% without ROSE, p=0.1),
      but the use of ROSE was associated with fewer lesions (mean 1.1 with ROSE vs. 1.6
      without ROSE, p<0.01) or aspirates (mean 2.3 with ROSE vs. 4.0 without ROSE,
      p<0.01). CONCLUSIONS: EBUS-TBNA provided a high diagnostic yield in SCLC with or
      without ROSE. EBUS-TBNA can be recommended for patients suspected to have SCLC,
      even if other diagnostic tests have failed.

PMID- 24853018
TI  - Relationship between the ratios of CD4/CD8 T-lymphocytes in the bronchoalveolar
      lavage fluid and lymph nodes in patients with sarcoidosis.
AB  - BACKGROUND: Evaluating the ratio of CD4/CD8 T-lymphocytes in the bronchoalveolar
      lavage fluid (BALF) is important for understanding the clinical and pathological
      conditions of patients with sarcoidosis. However, few studies have thus far
      demonstrated the usefulness of evaluating the relationship between the ratios of
      CD4/CD8 T-lymphocytes in the mediastinal lymph nodes and BALF. This study aimed
      to investigate and identify the relationships between CD4/CD8 T-lymphocyte ratio
      in the mediastinal lymph nodes and BALF in patients with sarcoidosis. METHODS:
      Thirty-three consecutive patients with sarcoidosis with enlarged mediastinal
      and/or hilar lymphadenopathy were enrolled in the study, and endobronchial
      ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and
      bronchoalveolar lavage (BAL) were simultaneously performed. The CD4/CD8 T
      lymphocyte ratios in the mediastinal lymph nodes and BALF were evaluated using
      immunohistochemistry and flow cytometry, respectively. RESULTS: The interobserver
      variability in the CD4/CD8 ratio in the mediastinal lymph nodes as determined by
      immunostaining was low, and the pathological and cytological profiles of T
      lymphocytes in the mediastinal and/or hilar lymph nodes and BALF were correlated
      in patients with sarcoidosis. Additionally, the CD4/CD8 T-lymphocyte ratios in
      BALF were significantly higher than those in the mediastinal lymph nodes.
      Importantly, non-caseating granulomas were detected at a high rate by using EBUS
      TBNA. CONCLUSIONS: Performing EBUS-TBNA in patients with sarcoidosis allows
      correct diagnosis as well as the estimation of the ratio of CD4/CD8 T-lymphocytes
      in BALF.

PMID- 24853019
TI  - Toxicity and efficacy of chemotherapy for non-small cell lung cancer with
      cavitary lesions.
AB  - BACKGROUND: Concurrent chemoradiation in stage III non-small cell lung cancer
      (NSCLC) patients with cavitary lesions is reported to cause serious lung
      complications and is a predictor of poor survival. However, the efficacy and
      toxicity associated with chemotherapy for advanced NSCLC patients with cavitary
      lesions is not clear. We investigated the toxicities, particularly hemoptysis and
      cavity infection, and efficacy associated with chemotherapy for NSCLC patients
      with cavitary lesions. METHODS: We retrospectively reviewed consecutive patients
      who received first-line chemotherapy, including platinum-based chemotherapy,
      single-agent chemotherapy, or epidermal growth factor receptor-tyrosine kinase
      inhibitors, at our institution between January 2008 and December 2010. RESULTS:
      We found tumor cavitation prior to treatment in 23 of 415 NSCLC patients (5.5%).
      The response rate of all the patients was 30%, and the median survival time (MST)
      was 8.9 months. The MST of the 15 patients treated with platinum-based
      chemotherapy was 11 months. Grade 1 bronchopulmonary hemorrhage occurred in 2
      patients. Grade 3 cavitary infection occurred in 2 patients, resulting in the
      discontinuation of chemotherapy. CONCLUSIONS: This study indicates that the
      toxicity of chemotherapy for NSCLC patients with cavitary lesions is tolerable;
      however, the development of cavitary infection should be carefully considered. In
      addition, this study suggests that the efficacy of chemotherapy for NSCLC
      patients with cavitary lesions is similar to the response rates reported in the
      literature; however, the survival of these patients may be worse than that for
      general NSCLC patients.

PMID- 24853021
TI  - BMPR2 gene mutation in pulmonary arteriovenous malformation and pulmonary
      hypertension: a case report.
AB  - The transforming growth factor-beta superfamily signaling pathway is thought to
      be involved in the pathogenesis of pulmonary arteriovenous malformation (PAVM).
      However, the association between bone morphogenetic protein receptor type 2
      (BMPR2) gene mutations and PAVM remains unclear. We present a case of concurrent
      PAVM and pulmonary arterial hypertension (PAH), with a deletion mutation in exon
      6 and exon 7 of the BMPR2 gene. Drug treatment for PAH improved the patient's
      hemodynamics and exercise capacity, but worsened oxygenation. This case suggests
      that BMPR2 gene mutation may be associated with the complex presentation of PAVM
      combined with PAH. 

PMID- 24853022
TI  - Reversed halo sign in pulmonary infarction with tumor emboli: a case report.
AB  - We describe the case of a 79-year-old woman with pulmonary infarction due to
      tumor emboli whose high-resolution CT (HRCT) scan demonstrated the reversed halo
      sign. The patient had gastric cancer and died because of cancer-related cerebral
      infarction. On autopsy, the central ground-glass area of the reversed halo sign
      on HRCT corresponded to pulmonary edema associated with alveolar septal capillary
      metastasis, whereas the peripheral ring-like consolidation consisted of a
      hemorrhagic infarct with tumor emboli. The present case is important because a
      detailed pathologic correlation with this unique HRCT appearance was revealed. 

PMID- 24853020
TI  - Phase II study of amrubicin combined with carboplatin for refractory relapsed
      small-cell lung cancer: North Japan Lung Cancer Group Trial 0802.
AB  - BACKGROUND: Amrubicin (AMR), a new anthracycline agent, has shown promising
      results for advanced small-cell lung cancer (SCLC), although the efficacy of AMR
      alone against refractory relapsed SCLC is insufficient. This study was conducted
      to evaluate the safety and efficacy of the combination of AMR and carboplatin
      (CBDCA) in patients with refractory relapsed SCLC. METHODS: Patients with
      advanced SCLC who relapsed within 90 days after the completion of first-line
      chemotherapy received AMR (30mg/m(2), days 1-3) and CBDCA (area under the curve
      4.0mgmL(-1)min(-1), day 1) every 3 weeks. The primary endpoint of this study was
      the overall response rate (ORR), and the secondary endpoints were progression
      free survival (PFS), overall survival, and the toxicity profile. Assuming that an
      ORR of 45% in eligible patients would indicate potential usefulness and an ORR of
      20% would be the lower limit of interest, with alpha=0.10 and beta=0.10, at least
      24 patients were required. RESULTS: Among 29 eligible patients, the ORR was 34%
      (90% confidence interval, 20-48). The median PFS was 3.5 months, whereas the
      median survival time was 7.3 months. The most common grade 3-4 toxicity was
      neutropenia (79%), although only one patient (3%) suffered from febrile
      neutropenia. Non-hematological toxicities were of moderate severity and no
      treatment-related death was observed. CONCLUSIONS: This is the first prospective
      study of AMR combined with CBDCA for refractory relapsed SCLC, which was
      effective and well tolerated. However, further investigation of this regimen is
      warranted.

PMID- 24853023
TI  - Morgagni hernia with respiratory failure aggravated by noninvasive positive
      pressure ventilation: a case report and overview of the literature.
AB  - An elderly woman diagnosed with multiple myeloma (MM) in 2007 had improved with
      chemotherapy. She had severe kyphosis and a diaphragmatic hernia (DH), but no
      respiratory symptoms. In 2011, because of thoracic deformity and emaciation, we
      advised her to continue the previously prescribed domiciliary noninvasive
      positive pressure ventilation (NPPV) therapy for chronic type II respiratory
      failure. However, she refused to continue NPPV. She was later admitted for
      deterioration in respiratory status and carbon dioxide (CO2) narcosis. We
      believed her low adherence to domiciliary NPPV caused CO2 narcosis; hence, we
      advised her to continue domiciliary NPPV and she complied. In May 2012, the now
      79-year-old patient was admitted for acute exacerbation of chronic respiratory
      failure and CO2 narcosis. Chest imaging suggested that DH had caused a
      deterioration of her status. She underwent laparoscopic diaphragmatic hernia
      repair. Operative findings revealed a retrosternal hernia sac, and she was
      diagnosed as having a Morgagni hernia (MH). Her respiratory status subsequently
      improved. We hypothesize that NPPV increased intra-abdominal pressure, thereby
      worsening the MH and exacerbating respiratory failure. We believe that clinicians
      should be cautious when prescribing NPPV for MH patients. 

PMID- 24853024
TI  - Three cases of mesalazine-induced pneumonitis with eosinophilia.
AB  - Oral mesalazine, or 5-aminosalicylate, is one of the first-choice medications for
      the treatment of ulcerative colitis and is commonly used for both induction and
      maintenance therapy. In a 6-month period, we treated three cases of mesalazine
      induced pneumonitis. In all three cases, computed tomography images revealed
      upper lobe dominant bilateral peripherally localized consolidations. Such images
      are commonly observed in patients with cryptogenic organizing pneumonia or
      chronic eosinophilic pneumonia. Computed tomography images for mesalazine-induced
      pneumonitis have been rarely reported in the literature. 

PMID- 24853025
TI  - Consolidation with a twisted appearance along the airways: a report of five cases
      of interstitial pneumonia.
AB  - High-resolution CT showed areas of airspace consolidation with a twisted
      appearance of the airways, along with areas of peribronchial ground-glass
      attenuation and traction bronchiectasis, in five patients with interstitial
      pneumonia. These areas of airspace consolidation were termed "twisted
      consolidation" (TwC). The five patients included two patients receiving treatment
      for rheumatoid arthritis (RA), one patient with newly diagnosed RA, and one
      patient who subsequently showed RA. Three patients showed improvement after
      steroid administration. An association of TwC with RA is suspected, but further
      studies are necessary. 

PMID- 24853026
TI  - Barodontalgias, dental and orofacial barotraumas: a survey in Swiss divers and
      caisson workers.
AB  - Changing ambient pressure can lead to medical conditions in body cavities filled
      with air. Intraoral pain elicited by changes in pressure is referred to as
      barodontalgia. Dental barotraumas are defined as pressure-induced damages of
      teeth and restorations. The pathophysiologic background so far is not completely
      clear. The present study deals with dental and orofacial symptoms which can occur
      as a result of pressure variations. With the aid of cantonal administrations,
      diving associations, and tunnel construction firms, 520 pressure-exposed
      individuals (499 scuba/ professional divers, 21 caisson workers operating at
      excess pressure) were questioned regarding dental problems. A personal interview
      was conducted with affected individuals. Problems in the dental area were
      experienced by 15% of all respondents. Toothaches were suffered by 10.2% of the
      participants. Tooth injuries occurred in 6.3% of all interviewees (26 fractured
      amalgam restorations, 4 crown fractures, 3 losses of tooth fragments). A
      proportion of 11.3% among the respondents complained about temporomandibular
      joint problems or mucosal irritations (for example aphthae) related to the
      mouthpieces. Barotraumas outside the dental area were incurred by 31.9% of the
      divers. Of these, 69.9% concerned the ears and 65.6% occurred during the descent.
      Based on the results obtained from the survey and taking into account the current
      literature, recommendations for the prevention of barotraumas in divers and
      caisson workers were prepared. Diagnostic exclusion of dental pathologies and
      avoidance of retentive reconstruction materials are important factors for the
      prevention of barodontalgias and dental barotraumas.

PMID- 24853028
TI  - Association of vitamin D receptor gene polymorphism with the risk of systemic
      lupus erythematosus.
AB  - Relationship between vitamin D receptor (VDR) gene polymorphism and the risk of
      systemic lupus erythematosus (SLE) from the published reports are still
      conflicting. This study was conducted to evaluate the relationship between VDR
      BsmI (rs1544410), Fok1 (rs2228570), ApaI (rs7975232) and TaqI (rs731236) gene
      polymorphism and the risk of SLE using meta-analysis method. The association
      studies were identified from PubMed and Cochrane Library on 1 March 2014, and
      eligible investigations were included and synthesized using meta-analysis method.
      Thirteen reports were recruited into this meta-analysis for the association of
      VDR gene polymorphism with SLE susceptibility. In this meta-analysis for overall
      populations, the BsmI B allele and bb genotype, Fok1 f allele and ff genotype,
      and ApaI aa genotype, were associated with the risk of SLE. In Asians, the BsmI B
      allele, BB genotype and bb genotype, Fok1 f allele and ff genotype were
      associated with the risk of SLE. In Africans, the BsmI B allele, BB genotype and
      bb genotype, Fok1 f allele and ff genotype, ApaI A allele, AA genotype and aa
      genotype were associated with the risk of SLE. However, VDR BsmI, Fok1, ApaI and
      TaqI gene polymorphism were not associated with the risk of SLE in Caucasians. In
      conclusion, the BsmI B allele and bb genotype, Fok1 f allele and ff genotype were
      associated with the risk of SLE in overall populations, and in Asians, but these
      associations were not found in Caucasians. However, more studies should be
      conducted to confirm it. 

PMID- 24853027
TI  - Antigenic peptide molecular recognition by the DRB1-DQB1 haplotype modulates
      multiple sclerosis susceptibility.
AB  - Multiple sclerosis (MS) is an autoimmune disease of the central nervous system
      that has a notably high incidence in Sardinia. Our study focuses on two HLA class
      II haplotypes associated with the disease in Sardinia, the rare predisposing
      DRB1*15:01-DQB1*06:02 and the widespread protective DRB1*16:01-DQB1*05:02. This
      framework enabled the highlighting of HLA binding pocket specificity and peptide
      recognition mechanisms by employing molecular dynamics simulations of the whole
      DRB1-DQB1 haplotype interacting with MBP- and EBV-derived peptides. We analyzed
      peptide-protein interaction networks and temporal evolution of the original
      complexes and after key amino acid mutations. The mutation G86V of the protective
      DRB1 allele exerted its effect mainly in the presence of the EBV viral peptide,
      with local and long range outcomes. However, the V38A mutation of the protective
      DQB1 showed a long range effect only in the case of the MBP myelin peptide. Our
      findings also demonstrate a DRB1/DQB1 complementary molecular recognition of
      peptides. This mechanism could provide a robust synergistic action and a
      differential role of DRB1 and DQB1 in tissues and in the time-steps towards
      autoimmunity. In addition, we demonstrate that negatively charged residues in
      pockets 4 and 9 play a role in MS susceptibility. Our findings are supported by
      recent experiments using a closely related MS animal model. Overall, our analysis
      confirms the role of the DRB1-DQB1 haplotype in conferring disease predisposition
      and could provide a valuable aid in designing optimal therapeutic peptides for MS
      therapy. 

PMID- 24853029
TI  - NFATc3 pathway participates in the process that 15-LO/15-HETE protects pulmonary
      artery smooth muscle cells against apoptosis during hypoxia.
AB  - Hypoxia activates nuclear factor of activated T cells isoforms c3 (NFATc3), a
      Ca(2+)-dependent transcription factor in murine pulmonary arteries (PAs), and
      NFATc3 has been proved to be implicated in hypoxia-induced pulmonary arterial
      smooth muscle cells (PASMCs) proliferation, but it remains unclear whether NFATc3
      acts on the apoptosis of PASMCs, an important step in PAs remodeling. Our
      laboratory has demonstrated that 15-hydroxyeicosatetraenoic acid (15-HETE) is a
      key factor in hypoxia-induced PA remodeling and can increase PASMC intracellular
      Ca(2+) ([Ca(2+)](i)) in rats. It is possible that NFATc3 is related with the
      function of 15-HETE anti-apoptosis during hypoxia. Our results identified that
      NFATc3 was mainly localized in rat PASMCs and was upregulated in PAs during
      hypoxia-induced rat pulmonary hypertension (PH), while this effect was inhibited
      by administration of nordihydroguaiaretic acid (NDGA), a 15-lipoxygenase (15-LO)
      inhibitor. Moreover, hypoxia and exogenous 15-HETE promoted the expression and
      nuclear translocation of NFATc3 in PASMCs, which was inhibited by NDGA or small
      interfering RNA targeted to rat 15-LO1 or 15-LO2. Furthermore, endogenous 15-HETE
      induced by hypoxia and exogenous 15-HETE suppressed serum deprivation-induced
      loss of rat PASMCs survival and prevented annexin V binding, mitochondrial
      membrane potential depolarization, DNA nick end labeling and chromatin
      condensation. Although all these effects were suppressed after the cells were
      treated with cyclosporin A (a calcineurin/NFAT inhibitor), it aggravated the
      apoptosis induced by serum deprivation. Thus, all these results indicate that 15
      HETE-mediated PASMCs anti-apoptosis in hypoxic PH via the Ca(2+)-NFATc3 pathway.

PMID- 24853030
TI  - Matched comparison of robot-assisted, laparoscopic and open radical prostatectomy
      regarding pathologic and oncologic outcomes in obese patients.
AB  - OBJECTIVES: To investigate pathological and oncological outcomes of obese
      patients who underwent robot-assisted radical prostatectomy (RARP) compared with
      laparoscopic radical prostatectomy (LRP) or open retropubic radical prostatectomy
      (RRP) since limited comparative data exist with regard to oncological and
      survival outcomes. METHODS: A total of 869 patients with body mass index >= 30
      from two academic centers were identified. A total of 194 patients who underwent
      RARP were propensity score (PS) matched 1:1 to LRP or RRP cases. PS-matching
      variables included prostate-specific antigen (PSA), biopsy Gleason score,
      clinical stage, surgeon experience, and nerve-sparing technique. Predictors of
      positive surgical margins (PSMs) were analyzed using logistic regression.
      Predictors of recurrence-free survival (RFS) were analyzed within Cox regression
      models. Overall survival was compared with RFS using the log-rank test. RESULTS:
      Pathologic Gleason scores <7, =7, and >7 were found in 24.2, 63.6, and 11.7 % of
      patients, respectively. There were no statistically significant differences
      related to pathologic stage or lymph node metastases between surgical techniques.
      PSM for pT2 disease were observed in 22.9, 17.4, and 19.3 % of patients
      undergoing RARP, LRP, and RRP, respectively (not significantly different).
      Preoperative PSA and clinical stage cT2 disease were independently associated
      with PSM. There were no significant differences in mean 3-year RFS for RARP, LRP,
      and RRP (87.4, 91.0, and 85.7 %). Biopsy Gleason score >7, PSM, and clinical
      stage two were independent predictors of decreased RFS. CONCLUSIONS: RARP
      demonstrates similar pathological and oncological results compared with LRP or
      RRP for obese patients.

PMID- 24853032
TI  - The History of the Data Systems AutoChemist(r) (ACH) and AutoChemist- PRISMA
      (PRISMA(r)): from 1964 to 1986.
AB  - OBJECTIVES: This paper presents the history of data system development steps
      (1964 - 1986) for the clinical analyzers AutoChemist(r), and its successor
      AutoChemist PRISMA(r) (PRogrammable Individually Selective Modular Analyzer). The
      paper also partly recounts the history of development steps of the minicomputer
      PDP 8 from Digital Equipment. The first PDP 8 had 4 core memory boards of 1 K
      each and was large as a typical oven baking sheet and about 10 years later, PDP 8
      was a "one chip microcomputer" with a 32 K memory chip. The fast developments of
      PDP 8 come to have a strong influence on the development of the data system for
      AutoChemist. Five major releases of the software were made during this period (1
      5 MIACH). RESULTS: The most important aims were not only to calculate the
      results, but also be able to monitor their quality and automatically manage the
      orders, store the results in digital form for later statistical analysis and
      distribute the results to the physician in charge of the patient using thesame
      computer as the analyzer. Another result of the data system was the ability to
      customize AutoChemist to handle sample identification by using bar codes and the
      presentation of results to different types of laboratories. CONCLUSIONS: Digital
      Equipment launched the PDP 8 just as a new minicomputer was desperately needed.
      No other known alternatives were available at the time. This was to become a key
      success factor for AutoChemist. That the AutoChemist with such a high capacity
      required a computer for data collection was obvious already in the early 1960s.
      That computer development would be so rapid and that one would be able to
      accomplish so much with a data system was even suspicious at the time. In total,
      75; AutoChemist (31) and PRISMA (44) were delivered Worldwide. The last PRISMA
      was delivered in 1987 to the Veteran Hospital Houston, TX USA.

PMID- 24853031
TI  - On determining factors for good research in biomedical and health informatics.
      Some lessons learned.
AB  - OBJECTIVE: What are the determining factors for good research in medical
      informatics or, from a broader perspective, in biomedical and health informatics?
      METHOD: From the many lessons learned during my professional career, I tried to
      identify a fair sampling of such factors. On the occasion of giving the IMIA
      Award of Excellence lecture during MedInfo 2013, they were presented for
      discussion. RESULTS: Sixteen determining factors (df) have been identified: early
      identification and promotion (df1), appropriate education (df2), stimulating
      persons and environments (df3), sufficient time and backtracking opportunities
      (df4), breadth of medical informatics competencies (df5), considering the
      necessary preconditions for good medical informatics research (df6), easy access
      to high-quality knowledge (df7), sufficient scientific career opportunities
      (df8), appropriate conditions for sustainable research (df9), ability to
      communicate and to solve problems (df10), as well as to convey research results
      (df11) in a highly inter- and multidisciplinary environment, ability to think for
      all and, when needed, taking the lead (df12), always staying unbiased (df13),
      always keeping doubt (df14), but also always trying to provide solutions (df15),
      and, finally, being aware that life is more (df16). CONCLUSIONS: Medical
      Informatics is an inter- and multidisciplinary discipline "avant la lettre".
      Compared to monodisciplinary research, inter- and multidisciplinary research does
      not only provide significant opportunities for solving major problems in science
      and in society. It also faces considerable additional challenges for medical
      informatics as a scientific field. The determining factors, presented here, are
      in my opinion crucial for conducting successful research and for developing a
      research career. Since medical informatics as a field has today become an
      important driving force for research progress, especially in biomedicine and
      health care, but also in fields like computer science, it may be helpful to
      consider such factors in relation with research and education in our discipline.

PMID- 24853033
TI  - The History of the AutoChemist(r): From Vision to Reality.
AB  - OBJECTIVES: This paper discusses the early history and development of a clinical
      analyser system in Sweden (AutoChemist, 1965). It highlights the importance of
      such high capacity system both for clinical use and health care screening. The
      device was developed to assure the quality of results and to automatically handle
      the orders, store the results in digital form for later statistical analyses and
      distribute the results to the patients' physicians by using the computer used for
      the analyser. RESULTS: The most important result of the construction of an
      analyser able to produce analytical results on a mass scale was the development
      of a mechanical multi-channel analyser for clinical laboratories that handled
      discrete sample technology and could prevent carry-over to the next test samples
      while incorporating computer technology to improve the quality of test results.
      The AutoChemist could handle 135 samples per hour in an 8-hour shift and up to 24
      possible analyses channels resulting in 3,200 results per hour. Later versions
      would double this capacity. Some customers used the equipment 24 hours per day.
      CONCLUSIONS: With a capacity of 3,000 to 6,000 analyses per hour, pneumatic
      driven pipettes, special units for corrosive liquids or special activities, and
      an integrated computer, the AutoChemist system was unique and the largest of its
      kind for many years. Its follower - The AutoChemist PRISMA (PRogrammable
      Individually Selective Modular Analyzer) - was smaller in size but had a higher
      capacity. Both analysers established new standards of operation for clinical
      laboratories and encouraged others to use new technologies for building new
      analysers.

PMID- 24853035
TI  - Commentaries on the IMIA Award of Excellence Lecture by Reinhold Haux.
AB  - The IMIA Yearbook editorial team asked five internationally renowned biomedical
      informaticians to respond to Prof. Haux's editorial. This paper summarizes their
      thoughts and responses. Contributions are ordered alphabetically by the
      contributor's last name. All authors provided an equal contribution to this
      manuscript. 

PMID- 24853034
TI  - Big data and biomedical informatics: a challenging opportunity.
AB  - Big data are receiving an increasing attention in biomedicine and healthcare. It
      is therefore important to understand the reason why big data are assuming a
      crucial role for the biomedical informatics community. The capability of handling
      big data is becoming an enabler to carry out unprecedented research studies and
      to implement new models of healthcare delivery. Therefore, it is first necessary
      to deeply understand the four elements that constitute big data, namely Volume,
      Variety, Velocity, and Veracity, and their meaning in practice. Then, it is
      mandatory to understand where big data are present, and where they can be
      beneficially collected. There are research fields, such as translational
      bioinformatics, which need to rely on big data technologies to withstand the
      shock wave of data that is generated every day. Other areas, ranging from
      epidemiology to clinical care, can benefit from the exploitation of the large
      amounts of data that are nowadays available, from personal monitoring to primary
      care. However, building big data-enabled systems carries on relevant implications
      in terms of reproducibility of research studies and management of privacy and
      data access; proper actions should be taken to deal with these issues. An
      interesting consequence of the big data scenario is the availability of new
      software, methods, and tools, such as map-reduce, cloud computing, and concept
      drift machine learning algorithms, which will not only contribute to big data
      research, but may be beneficial in many biomedical informatics applications. The
      way forward with the big data opportunity will require properly applied
      engineering principles to design studies and applications, to avoid
      preconceptions or over-enthusiasms, to fully exploit the available technologies,
      and to improve data processing and data management regulations. 

PMID- 24853036
TI  - Healthcare information technology infrastructures in Turkey.
AB  - OBJECTIVES: The objective of this paper is to describe some of the major
      healthcare information technology (IT) infrastructures in Turkey, namely, Saglik
      Net (Turkish for "Health-Net"), the Centralized Hospital Appointment System, the
      Basic Health Statistics Module, the Core Resources Management System, and the e
      prescription system of the Social Security Institution. International
      collaboration projects that are integrated with Saglik-Net are also briefly
      summarized. METHODS: The authors provide a survey of the some of the major
      healthcare IT infrastructures in Turkey. RESULTS: Saglik-Net has two main
      components: the National Health Information System (NHIS) and the Family Medicine
      Information System (FMIS). The NHIS is a nation-wide infrastructure for sharing
      patients' Electronic Health Records (EHRs). So far, EHRs of 78.9 million people
      have been created in the NHIS. Similarly, family medicine is operational in the
      whole country via FMIS. Centralized Hospital Appointment System enables the
      citizens to easily make appointments in healthcare providers. Basic Health
      Statistics Module is used for collecting information about the health status,
      risks and indicators across the country. Core Resources Management System speeds
      up the flow of information between the headquarters and Provincial Health
      Directorates. The e-prescription system is linked with Saglik-Net and seamlessly
      integrated with the healthcare provider information systems. Finally, Turkey is
      involved in several international projects for experience sharing and
      disseminating national developments. CONCLUSION: With the introduction of the
      "Health Transformation Program" in 2003, a number of successful healthcare IT
      infrastructures have been developed in Turkey. Currently, work is going on to
      enhance and further improve their functionality.

PMID- 24853037
TI  - Big3. Editorial.
AB  - OBJECTIVES: To provide an editorial introduction into the 2014 IMIA Yearbook of
      Medical Informatics with an overview of the content, the new publishing scheme,
      and upcoming 25th anniversary. METHODS: A brief overview of the 2014 special
      topic, Big Data - Smart Health Strategies, and an outline of the novel publishing
      model is provided in conjunction with a call for proposals to celebrate the 25th
      anniversary of the Yearbook. RESULTS: 'Big Data' has become the latest buzzword
      in informatics and promise new approaches and interventions that can improve
      health, well-being, and quality of life. This edition of the Yearbook
      acknowledges the fact that we just started to explore the opportunities that 'Big
      Data' will bring. However, it will become apparent to the reader that its
      pervasive nature has invaded all aspects of biomedical informatics - some to a
      higher degree than others. It was our goal to provide a comprehensive view at the
      state of 'Big Data' today, explore its strengths and weaknesses, as well as its
      risks, discuss emerging trends, tools, and applications, and stimulate the
      development of the field through the aggregation of excellent survey papers and
      working group contributions to the topic. CONCLUSIONS: For the first time in
      history will the IMIA Yearbook be published in an open access online format
      allowing a broader readership especially in resource poor countries. For the
      first time, thanks to the online format, will the IMIA Yearbook be published
      twice in the year, with two different tracks of papers. We anticipate that the
      important role of the IMIA yearbook will further increase with these changes just
      in time for its 25th anniversary in 2016.

PMID- 24853038
TI  - Low-complexity intrauterine pressure estimation using the Teager energy operator
      on electrohysterographic recordings.
AB  - Monitoring the progression of maternal uterine activity provides important
      prognostic information during pregnancy and parturition. Currently used methods
      for intrauterine pressure (IUP) measurement are unsuitable for long-term
      observation of uterine activity. The abdominally measured electrohysterogram
      (EHG) provides a non-invasive alternative to the existing methods for long-term
      ambulatory uterine contraction monitoring. A new low-complexity method for IUP
      estimation based on the Teager energy (TE) operator is proposed. The TE operator
      was used as it mimics the physiologic phenomena underlying the generation of the
      EHG signals. Several EHG signal analysis methods for IUP estimation from the
      literature are compared with the new TE method. The comparison is based on
      correlation and root mean square error of the IUP estimate with the gold standard
      internally measured IUP as well as their respective computational complexity. The
      proposed method results in a superior IUP estimation accuracy and complexity
      compared to state-of-the-art methods from the literature, with a complexity as
      much as 55 times lower. Therefore, the proposed method offers a valuable new
      option for long-term ambulatory uterine monitoring. 

PMID- 24853040
TI  - High temperature heat source generation with quasi-continuous wave semiconductor
      lasers at power levels of 6 W for medical use.
AB  - We investigate a technology to create a high temperature heat source on the tip
      surface of the glass fiber proposed for medical surgery applications. Using 4 to
      6 W power level semiconductor lasers at a wavelength of 980 nm, a laser coupled
      fiber tip was preprocessed to contain a certain amount of titanium oxide powder
      with a depth of 100 MUm from the tip surface so that the irradiated low laser
      energy could be perfectly absorbed to be transferred to thermal energy. Thus, the
      laser treatment can be performed without suffering from any optical
      characteristic of the material. A semiconductor laser was operated quasi
      continuous wave mode pulse time duration of 180 ms and >95% of the laser energy
      was converted to thermal energy in the fiber tip. Based on two-color thermometry,
      by using a gated optical multichannel analyzer with a 0.25 m spectrometer in
      visible wavelength region, the temperature of the fiber tip was analyzed. The
      temperature of the heat source was measured to be in excess 3100 K.

PMID- 24853041
TI  - Analytical strategies based on quantum dots for heavy metal ions detection.
AB  - Heavy metal contamination is one of the major concerns to human health because
      these substances are toxic and retained by the ecological system. Therefore, in
      recent years, there has been a pressing need for fast and reliable methods for
      the analysis of heavy metal ions in environmental and biological samples. Quantum
      dots (QDs) have facilitated the development of sensitive sensors over the past
      decade, due to their unique photophysical properties, versatile surface chemistry
      and ligand binding ability, and the possibility of the encapsulation in different
      materials or attachment to different functional materials, while retaining their
      native luminescence property. This paper comments on different sensing strategies
      with QD for the most toxic heavy metal ions (i.e., cadmium, Cd2+; mercury, Hg2+;
      and lead, Pb2+). Finally, the challenges and outlook for the QD-based sensors for
      heavy metals ions are discussed.

PMID- 24853039
TI  - Accessibility and utilization patterns of a mobile medical clinic among
      vulnerable populations.
AB  - We mapped mobile medical clinic (MMC) clients for spatial distribution of their
      self-reported locations and travel behaviors to better understand health-seeking
      and utilization patterns of medically vulnerable populations in Connecticut.
      Contrary to distance decay literature, we found that a small but significant
      proportion of clients was traveling substantial distances to receive repeat care
      at the MMC. Of 8404 total clients, 90.2% lived within 5 miles of a MMC site, yet
      mean utilization was highest (5.3 visits per client) among those living 11-20
      miles of MMCs, primarily for those with substance use disorders. Of clients
      making >20 visits, 15.0% traveled >10 miles, suggesting that a significant
      minority of clients traveled to MMC sites because of their need-specific
      healthcare services, which are not only free but available at an acceptable and
      accommodating environment. The findings of this study contribute to the important
      research on healthcare utilization among vulnerable population by focusing on
      broader dimensions of accessibility in a setting where both mobile and fixed
      healthcare services coexist. 

PMID- 24853042
TI  - Albuminuria and sodiuria in IUGR children.
AB  - OBJECTIVE: Intrauterine growth restriction (IUGR) is associated with
      hyperfiltration, glomerulosclerosis and albuminuria. Albuminuria may further lead
      to tubulointerstitial inflammation, fibrosis and tubular atrophy. The time at
      which this may occur is unknown. This study was designed to assess the
      relationship between glomerular and tubular damage in IUGR children. METHODS: We
      enrolled 50 children, 25 IUGR, categorized by estimated fetal weight <10th
      percentile and umbilical artery pulsatility index >2 SD, and 25 appropriate for
      gestational age (AGA) controls at 18 months of age. We compared albuminuria among
      IUGR and AGA children, to assess the relationship between albuminuria and
      contemporary sodium and lysozyme excretion, as a measure of tubular damage.
      RESULTS: The albumin-creatinine (mg/g) and sodium-creatinine (MUM/L) ratios (3.12
      and 441.3, versus 1.39 and 226.1 in AGA; p = 0.002 and p = 0.012, respectively)
      were significantly higher in the IUGR subjects compared with AGA children, and
      significantly correlated (rho = 0.593, p = 0.002). Conversely, urinary lysozyme
      was undetectable or in normal excretion range. CONCLUSIONS: Our results show
      glomerulosclerosis and albuminuria in IUGR children aged 18 months. Elevated
      sodium excretion in the absence of abnormal lysozymuria may represent a
      epiphenomenon of glomerulosclerosis and of albuminuria.

PMID- 24853044
TI  - Specific rotation of monosaccharides: a global property bringing local
      information.
AB  - Carbohydrates generally occur in several conformations that may differ among
      themselves by energy values that are smaller than the accuracy of the most
      sophisticated theoretical methods used to determine them. In addition, the
      preferential orientations of the hydroxyl groups of these molecules cannot be
      identified by any experimental technique. Therefore, a method that is able to
      validate the absolute conformations (i.e., consisting of the orientations of the
      hydroxyl groups) of carbohydrates would be helpful to improve our knowledge about
      monosaccharides. SR has been used for this purpose, and here, we present a test
      to measure the specific rotation (SR) ability of a molecule that possesses not
      only many conformations, but also four adjacent chiral centers. The results show
      that the final SR value is a weighted average of a global property (obtained for
      each conformation), and the latter by its turn is influenced by each chiral
      center in a multi chiral system. By comparing the SR values calculated for the
      most abundant anomers of xylopyranose with those of the corresponding monochiral
      analogs obtained by saturation of three different chiral centers each time, the
      influence of each center on the global property is confirmed. 

PMID- 24853043
TI  - Lactobacillus acidophilus NCFM affects colonic mucosal opioid receptor expression
      in patients with functional abdominal pain - a randomised clinical study.
AB  - BACKGROUND: In a recent double-blinded clinical trial, the probiotic combination
      of Lactobacillus acidophilus NCFM (L-NCFM) and B-LBi07 reduced bloating symptoms
      in patients with functional bowel disorders; an effect more evident in those who
      reported abdominal pain. In mice, L-NCFM but not B-LBi07 induced colonic mu
      opioid receptor (MOR) and cannabinoid receptor 2 (CB2) expression, and reduced
      visceral sensitivity. AIMS: To determine if L-NCFM was the active component in
      the clinical trial and to investigate the mechanism of action in humans with mild
      to moderate abdominal pain. METHODS: Caucasian women (n = 20) 18-70 years with
      mild to moderate abdominal pain were enrolled in a double-blind, two-armed,
      single-centre study. Patients were given either L-NCFM alone or in combination
      with B-LBi07 for 21 days at a total dose of 2 * 10(10) CFU b.d. Colonic biopsies
      were collected during unsedated, unprepped flexible sigmoidoscopy before and at
      the end of probiotic consumption. mRNA and immunostaining were then performed on
      these biopsies. Patients kept symptom diaries for the 7 days prior to starting
      probiotic therapy and for the last 7 days of therapy. RESULTS: L-NCFM alone, but
      not with B-LBi07, induced colonic MOR mRNA and protein expression, as well as
      downstream signalling, as measured by enterocyte STAT3-phosphorylation. In
      contrast, CB2 expression was decreased. Both treatment groups trended towards
      improvement in symptoms, but the study was insufficiently powered to draw
      meaningful conclusions. CONCLUSIONS: Lactobacillus acidophilus NCFM modulates mu
      opioid receptor expression and activity, while the combination of L-NCFM and B
      LBi07 does not. This study provides a possible mechanism for action by which
      probiotics modulates pain sensation in humans (Clinical Trial Number:
      NCT01064661).

PMID- 24853047
TI  - Determination of size of molecular clusters of ethanol by means of NMR
      diffusometry and hydrodynamic calculations.
AB  - The microscopic structure of ethanol in the liquid state is characterized as a
      dynamic equilibrium of hydrogen-bonded clusters of different sizes and
      topologies. We have developed a novel method for determination of the average
      size of the clusters that combines the measurement of diffusion coefficient by
      means of NMR diffusometry technique and hydrodynamic simulations. The approach
      includes the use of HydroNMR [J. Garcia de la Torre, M. L. Huertas, and B.
      Carrasco, J. Magn. Reson. 147, 2000, 138] for small molecules, which is attained
      here by the calibration procedure using a dilute solution of tetramethylsilane.
      It is thus possible to correlate the experimentally determined diffusion
      coefficient of ethanol with calculated diffusion coefficients of the modeled
      clusters of different sizes. We found that average size of the clusters in 0.16 M
      solution of ethanol in n-hexane corresponds to the monomer above 300 K and to the
      pentamer/hexamer below 240 K. The clusters in the case of 0.44 M solution are
      generally slightly larger, from the average size corresponding to the dimer at
      320 K and the hexamer at 210 K. 

PMID- 24853045
TI  - In-utero infection with HIV-1 associated with suppressed lymphoproliferative
      responses at birth.
AB  - In-utero exposure to HIV-1 may affect the immune system of the developing child
      and may induce HIV-1-specific immune responses, even in the absence of HIV-1
      infection. We evaluated lymphoproliferative capacity at birth among 40 HIV-1
      uninfected infants born to HIV-1-infected mothers and 10 infants who had acquired
      HIV-1 in utero. Cord blood mononuclear cells were assayed using [(3) H]-thymidine
      incorporation for proliferation in response to HIV-1 p55-gag and the control
      stimuli phytohaemagglutinin (PHA), Staphylococcus enterotoxin B (SEB) and
      allogeneic cells. In response to HIV-1 p55-gag, eight (20%) HIV-1-exposed,
      uninfected (EU) infants had a stimulation index (SI) >= 2 and three (30%) in
      utero HIV-1 infected infants had SI >=2. The frequency and magnitude of responses
      to HIV-1 p55-gag were low overall, and did not differ statistically between
      groups. However, proliferative responses to control stimuli were significantly
      higher in EU infants than in infants infected in utero, with a median SI in
      response to PHA of 123 [interquartile range (IQR) 77-231] versus 18 (IQR 4-86)
      between EU and infected infants, respectively (P < 0.001). Among infected
      infants, gestational maturity was associated with the strength of HIV-1 p55-gag
      response (P < 0.001); neither maternal nor infant HIV-1 viral load was
      associated. In summary, EU and HIV-1-infected infants mounted HIV-1-specific
      lymphoproliferative responses at similar rates (20-30%), and although global
      immune function was preserved among EU infants, neonatal immune responses were
      significantly compromised by HIV-1 infection. Such early lymphoproliferative
      compromise may, in part, explain rapid progression to AIDS and death among HIV-1
      infected infants.

PMID- 24853046
TI  - Impaired compensatory beta-cell function and growth in response to high-fat diet
      in LDL receptor knockout mice.
AB  - In this study, we investigated the effect of low density lipoprotein receptor
      (LDLr) deficiency on gap junctional connexin 36 (Cx36) islet content and on the
      functional and growth response of pancreatic beta-cells in C57BL/6 mice fed a
      high-fat (HF) diet. After 60 days on regular or HF diet, the metabolic state and
      morphometric islet parameters of wild-type (WT) and LDLr-/- mice were assessed.
      HF diet-fed WT animals became obese and hypercholesterolaemic as well as
      hyperglycaemic, hyperinsulinaemic, glucose intolerant and insulin resistant,
      characterizing them as prediabetic. Also they showed a significant decrease in
      beta-cell secretory response to glucose. Overall, LDLr-/- mice displayed greater
      susceptibility to HF diet as judged by their marked cholesterolaemia, intolerance
      to glucose and pronounced decrease in glucose-stimulated insulin secretion. HF
      diet induced similarly in WT and LDLr-/- mice, a significant decrease in Cx36
      beta-cell content as revealed by immunoblotting. Prediabetic WT mice displayed
      marked increase in beta-cell mass mainly due to beta-cell
      hypertrophy/replication. Nevertheless, HF diet-fed LDLr-/- mice showed no
      significant changes in beta-cell mass, but lower islet-duct association
      (neogenesis) and higher beta-cell apoptosis index were seen as compared to
      controls. The higher metabolic susceptibility to HF diet of LDLr-/- mice may be
      explained by a deficiency in insulin secretory response to glucose associated
      with lack of compensatory beta-cell expansion.

PMID- 24853048
TI  - Whole-exome sequencing confirmation of a novel heterozygous mutation in RUNX1 in
      a pregnant woman with platelet disorder.
AB  - We describe a successful pregnancy and delivery in a patient with platelet
      disorder. Prophylactic platelet transfusions ensured that there were no bleeding
      complications during and after cesarean section. Following delivery, we performed
      whole exome sequencing, using next generation sequencing, to analyze the DNA
      samples of the patient and her family, and to identify the disease-causing
      mutation or variant. To identify de-novo mutations systematically, we also
      analyzed DNA isolated from the parents of the patient and the neonate. We
      successfully identified a causative novel mutation c.419 G > A (p.S140N) in RUNX1
      in the patient and the neonate. Mutations of RUNX1 have been reported to be
      associated with familial platelet disorder and with a predisposition for
      myelodysplasia and/or acute myeloid leukemia. The patient and the neonate require
      careful long-term hematological follow-up. Identification of mutations by a
      through whole-exome analysis using next-generation sequencing may be useful in
      the determination of a long-term follow-up schedule for the patient. 

PMID- 24853049
TI  - "Advances in the surgical management of bone tumors".
AB  - Bone tumor surgery is extremely challenging, particularly when tumors are located
      in tightly confined anatomical areas and abutting critical organs and
      neurovascular structures. Tumor resection requires good cutting accuracy to
      ensure safety, to achieve negative margins, and to preserve critical structures
      when possible. The purpose of this paper was to review the literature on the
      surgical advances for bone tumor surgery published within the last year. The
      majority of literature identified focused on computer-assisted surgical
      approaches. There is increasing evidence that 3D navigation plays an important
      role in the resection of bone tumors. Reconstruction materials that encourage
      healing and prevent infections are also in development. Optimal care includes
      execution of a well-developed pre-operative plan using a multidisciplinary
      approach led by the orthopaedic oncologist. 

PMID- 24853050
TI  - Comparison of intervention methods for reducing human exposure to Mycobacterium
      bovis through milk in pastoralist households of Tanzania.
AB  - Bovine tuberculosis (bTB), caused by Mycobacterium bovis, is a disease of
      zoonotic concern, especially in countries with no control programs in livestock
      and where routine pasteurization of milk is not practiced. In Tanzania, bTB is
      widespread in livestock and has been diagnosed in humans; however, herd bTB
      testing is primarily carried out for bTB-free certification in commercial dairy
      herds at the expense of the dairy cattle owner. For rural livestock holders, such
      an expense is prohibitive, and consequently there is no control of bTB in most
      areas. Although effective long-term solutions to control bTB in livestock are
      desirable, there is a need to assess the effect of preventive measures on
      reducing human exposure to bTB in such settings. We utilized locally relevant
      cattle herd characteristics and management data from the Health for Animals and
      Livelihood Improvement (HALI) project in south-central Tanzania to build a Reed
      Frost model that compared the efficacy of alternative methods aimed at reducing
      the exposure of humans to infectious milk from a typical pastoralist cattle herd.
      During a 10-year simulation period, the model showed that boiling milk 80% of the
      time is necessary to obtain a reduction in liters of infectious milk
      approximately equivalent to what would be obtained with a standard 2-year testing
      and removal regimen, and that boiling milk was more effective than animal test
      and removal early in the time period. In addition, even with testing and removing
      infected cattle, a residual risk of exposure to infectious milk remained due to
      imperfect sensitivity of the skin test and a continuous risk of introduction of
      infectious animals from other herds. The model was sensitive to changes in
      initial bTB prevalence but not to changes in herd size. In conclusion, continuous
      complimentary treatment of milk may be an effective strategy to reduce human
      exposure to M. bovis-infected milk in settings where bTB is endemic and a
      comprehensive bTB control program is yet to be implemented. 

PMID- 24853051
TI  - Efficacy of fipronil (1.0 mg/kg) against Rhipicephalus (Boophilus) microplus
      strains resistant to ivermectin (0.63 mg/kg).
AB  - The present study aimed to evaluate the efficacy of fipronil (1 mg/kg) against
      three strains of ivermectin-resistant Rhipicephalus (Boophilus) microplus (R.
      (B.) microplus), naturally infesting cattle from different states of Brazil.
      Three rural properties with a history of macrocyclic lactones ineffectiveness
      against the cattle tick, and low frequency use of fipronil in the herd, were
      selected for the study. The animals were randomized according to the mean tick
      counts, performed on days -3, -2 and -1, into three groups with 10 animals each:
      T01, control (saline solution); T02, subcutaneous ivermectin (0.63 mg/kg) and
      T03, topical fipronil (1 mg/kg). Treatment was performed on day 0. Counts of
      partially engorged female ticks were performed on days 3, 7 and 14 post-treatment
      (DPT), and then every 7 days until the 49th DPT. In all three experiments, it was
      possible to diagnose resistance of R. (B.) microplus to ivermectin (0.63 mg/kg).
      The maximum efficacy (arithmetic mean) obtained for ivermectin was 64% in
      experiment II. On the other hand, the formulation containing fipronil (1 mg/kg)
      reached high efficacy values (>=97%) in all three experiments. The results from
      all experiments in this study demonstrate the high efficacy of 1mg/kg fipronil,
      administered pour-on in naturally infested cattle, against strains of R. (B.)
      microplus that are resistant to 630 mcg/kg ivermectin.

PMID- 24853053
TI  - mRNA levels of BACE1 and its interacting proteins, RTN3 and PPIL2, correlate in
      human post mortem brain tissue.
AB  - beta-Site amyloid precursor protein cleaving enzyme (BACE1) is the rate-limiting
      enzyme for production of Abeta peptides, proposed to drive the pathological
      changes found in Alzheimer's disease (AD). Reticulon 3 (RTN3) is a negative
      modulator of BACE1 (beta-secretase) proteolytic activity, while peptidylprolyl
      isomerase (cyclophilin)-like 2 (PPIL2) positively regulated BACE1 gene expression
      in a cell-based assay. This study aimed to analyze RTN3 and PPIL2 mRNA levels in
      four brain regions from individuals with AD and controls. BACE1 mRNA had been
      previously quantified in the samples, as had glial fibrillary acidic protein
      (GFAP) and neuron-specific enolase (NSE), to track changing cell populations in
      the tissue. mRNA levels in the human post mortem brain tissue were assayed using
      quantitative real-time polymerase chain reaction (qPCR) and qbase(PLUS),
      employing validated stably expressed reference genes. No differences in RTN3 or
      PPIL2 mRNA levels were found in individuals with AD, compared to controls. Both
      RTN3 and PPIL2 mRNA levels correlated significantly with BACE1 mRNA and all three
      showed similar disease stage-dependent changes with respect to NSE and GFAP.
      These findings indicated that the in vitro data demonstrating an effect of PPIL2
      on BACE1 expression have functional relevance in vivo. Further research into
      BACE1-interacting proteins could provide a fruitful approach to the modulation of
      this protease and consequently Abeta production. 

PMID- 24853052
TI  - Differential effects of aging on dendritic spines in visual cortex and prefrontal
      cortex of the rhesus monkey.
AB  - Aging decreases the density of spines and the proportion of thin spines in the
      non-human primate (NHP) dorsolateral prefrontal cortex (dlPFC). In this study, we
      used confocal imaging of dye-loaded neurons to expand upon previous results
      regarding the effects of aging on spine density and morphology in the NHP dlPFC
      and compared these results to the effects of aging on pyramidal neurons in the
      primary visual cortex (V1). We confirmed that spine density, and particularly the
      density of thin spines, decreased with age in the dlPFC of rhesus monkeys.
      Furthermore, the average head diameter of non-stubby spines in the dlPFC was a
      better predictor than chronological age of the number of trials required to reach
      criterion on both the delayed response test of visuospatial working memory and
      the delayed nonmatching-to-sample test of recognition memory. By contrast, total
      spine density was lower on neurons in V1 than in dlPFC, and neither total spine
      density, thin spine density, nor spine size in V1 was affected by aging. Our
      results highlight the importance and selective vulnerability of dlPFC thin spines
      for optimal prefrontal-mediated cognitive function. Understanding the nature of
      the selective vulnerability of dlPFC thin spines as compared to the resilience of
      thin spines in V1 may be a promising area of research in the quest to prevent or
      ameliorate age-related cognitive decline. 

PMID- 24853054
TI  - Connections of the magnocellular medial preoptic nucleus (MPN mag) in male Syrian
      hamsters. II. The efferents.
AB  - The magnocellular medial preoptic nucleus (MPN mag) plays a critical role in the
      regulation of male copulatory behavior in the Syrian hamster. Our study of the
      afferents are consistent with the hypothesis that the MPN mag receives input from
      areas in the chemosensory pathway and nuclear groups that contain receptors for
      gonadal steroids (Wang and Swann, 2006). The goal of the present study is to
      identify targets of the MPN mag by describing the location of labeled fibers
      following an injection of biotinylated dextran amine (BDA) into the MPN mag. Our
      results indicate that targets of the MPN mag include: (1) brainstem nuclei
      implicated in regulating male mating behavior in other species, such as the
      periaqueductal gray, deep mesencephalic nucleus, retrorubral field, ventral
      tegmental area and lateral paragigantocellular nucleus and (2) steroid
      concentrating nuclei in the septum, preoptic area and hypothalamus. The lack of
      projections from the MPN mag to its chemosensory afferents indicate that the
      connections of the MPN mag with the posterior medial bed nucleus of the stria
      terminalis, medial and anterior cortical nuclei of the amygdala are
      unidirectional, and that chemosensory information flows from the medial amygdala
      and bed nucleus of the stria terminalis (BST) to the MPN mag. The bidirectional
      nature of the connections between the MPN mag and steroid-concentrating nuclei
      suggest that the MPN mag may influence the function of a steroid-concentrating
      network that regulates behaviors. Together these results support the hypothesis
      that the MPN mag regulates male mating behavior by integrating chemosensory and
      hormonal signals and relaying this information to brainstem areas that control
      motor output. 

PMID- 24853055
TI  - Risk factors for cytomegalovirus gastrointestinal diseases in adult patients with
      cancer.
AB  - Cytomegalovirus (CMV) gastrointestinal (GI) disease has been noticed frequently
      in cancer patients, causing abdominal pain, diarrhea, and GI bleeding. However,
      little is known about its actual incidence, clinical presentation, and the risk
      factors for its development among cancer patients. To answer these questions, we
      analyzed all cases that occurred during an 18-year period at our center. A case
      control study was performed to identify risk factors for CMV GI disease.
      Electronic medical records were reviewed from individuals who were admitted and
      diagnosed with CMV GI disease during the period of January 1995 through March
      2013 at a tertiary care center. Two CMV disease-free cancer patients were matched
      as controls. A total of 98 episodes of CMV GI disease were included in this
      study, and the overall incidence rate was 52.5 per 100,000 cancer patients, with
      an increasing trend throughout the study period. According to multivariate
      analysis, male sex, low body mass index, lymphopenia, hematological malignancy,
      and steroid use and red blood cell transfusion within 1 month prior to the CMV
      disease were identified to be independent risk factors. Among these factors, RBC
      transfusion showed the highest odds ratio (OR = 5.09). Male sex, low body mass
      index, lymphopenia, hematological malignancy, steroid use, and red blood cell
      transfusion within 1 month prior to the CMV disease diagnosis were independent
      risk factors for the development of CMV GI disease in adult patients with cancer.

PMID- 24853056
TI  - Serum annexin A2 levels in acute brucellosis and brucellar spondylodiscitis.
AB  - Brucellosis is a chronic granulomatous infection and may present with various
      clinical manifestations. Brucellar spondylodiscitis symptoms are initially subtle
      and nonspecific. Annexin A2 (ANXA2) is involved in various biological functions,
      including osteoclast formation, bone resorption, and cell growth regulation. In
      this study, we aimed to determine the clinical significance of serum ANXA2 levels
      in acute brucellosis and brucellar spondylodiscitis. This prospective study
      included 96 acute brucellosis patients and 51 healthy controls. Acute brucellosis
      was diagnosed by a 1/160 or higher titer in a standard tube agglutination (STA)
      test or a four-fold increase in titers between two STA tests performed two weeks
      apart in the presence of clinical symptoms within the last eight weeks and/or
      growth of Brucella spp. in appropriately prepared culture media. ANXA2 levels
      were determined with an enzyme-linked immunosorbent assay (ELISA). Forty (41.7 %)
      of 96 acute brucellosis patients were male and 56 (58.3 %) were female. Serum
      ANXA2 levels were elevated in patients compared to healthy controls (p = 0.001).
      Eighteen of 96 (18.7 %) acute brucellosis patients had brucellar
      spondylodiscitis. The serum ANXA2 levels of patients with brucellar
      spondylodiscitis were higher than those of patients with acute disease without
      brucellar spondylodiscitis (p = 0.001). ANXA2, C-reactive protein (CRP), and
      erythrocyte sedimentation rate (ESR) values were elevated in the brucellar
      spondylodiscitis group compared to patients without brucellar spondylodiscitis.
      Serum ANXA2 measurement together with ESR and CRP is thought to be indicative in
      the diagnosis of brucellar spondylodiscitis, a common complication of
      brucellosis. 

PMID- 24853057
TI  - Electroformation of Janus and patchy capsules.
AB  - Janus and patchy particles have designed heterogeneous surfaces that consist of
      two or several patches with different materials properties. These particles are
      emerging as building blocks for a new class of soft matter and functional
      materials. Here we introduce a route for forming heterogeneous capsules by
      producing highly ordered jammed colloidal shells of various shapes with domains
      of controlled size and composition. These structures combine the functionalities
      offered by Janus or patchy particles, and those given by permeable shells such as
      colloidosomes. The simple assembly route involves the synergetic action of
      electro-hydrodynamic flow and electro-coalescence. We demonstrate that the method
      is robust and straightforwardly extendable to production of multi-patchy
      capsules. This forms a starting point for producing patchy colloidosomes with
      domains of anisotropic chemical surface properties, permeability or mixed liquid
      solid phase domains, which could be exploited to produce functional emulsions,
      light and hollow supra-colloidosome structures, or scaffolds. 

PMID- 24853058
TI  - Feedback processing in adolescence: an event-related potential study of age and
      gender differences.
AB  - Adolescence has frequently been characterized as a period of increased risk
      taking, which may be largely driven by maturational changes in neural areas that
      process incentives. To investigate age- and gender-related differences in reward
      processing, we recorded event-related potentials (ERPs) from 80 participants in a
      gambling game, in which monetary wins and losses were either large or small. We
      measured two ERP components: the feedback-related negativity (FRN) and the
      feedback P3 (fP3). The FRN was sensitive to the size of a win in both adult (aged
      23-35 years) and adolescent (aged 13-17 years) males, but not in females. Small
      wins appeared to be less rewarding for males than for females, which may in part
      explain more approach-driven behavior in males in general. Furthermore,
      adolescent boys showed both delayed FRNs to high losses and less differentiation
      in FRN amplitude between wins and losses in comparison to girls. The fP3, which
      is thought to index the salience of the feedback at a more conscious level than
      the FRN, was also larger in boys than in girls. Taken together, these results
      imply that higher levels of risk taking that are commonly reported in adolescent
      males may be driven both by hypersensitivity to high rewards and insensitivity to
      punishment or losses.

PMID- 24853059
TI  - The cognitive behavioural prevention of suicide in psychosis: a clinical trial.
AB  - BACKGROUND: Suicide behaviour in psychosis is a significant clinical and social
      problem. There is a dearth of evidence for psychological interventions designed
      to reduce suicide risk in this population. AIMS: To evaluate a novel, manualised,
      cognitive behavioural treatment protocol (CBSPp) based upon an empirically
      validated theoretical model. METHODS: A randomly controlled trial with
      independent and masked allocated and assessment of CBSPp with TAU (n=25, 24
      sessions) compared to TAU alone (n=24) using standardised assessments. Measures
      of suicide probability, and suicidal ideation were the primary outcomes and
      measures of hopelessness, depression, psychotic symptoms, functioning, and self
      esteem were the secondary outcomes, assessed at 4 and 6 months follow-up.
      RESULTS: The CBSPp group improved differentially to the TAU group on two out of
      three primary outcome measures of suicidal ideation and suicide probability, and
      on secondary outcomes of hopelessness related to suicide probability, depression,
      some psychotic symptoms and self-esteem. CONCLUSIONS: CBSPp is a feasible
      intervention which has the potential to reduce proxy measures of suicide in
      psychotic patients.

PMID- 24853060
TI  - Using self-determination theory to understand motivation deficits in
      schizophrenia: the 'why' of motivated behavior.
AB  - Self-determination theory (SDT) provides a model for understanding motivation
      deficits in schizophrenia, and recent research has focused on problems with
      intrinsic motivation. However, SDT emphasizes that motivated behavior results
      from three different factors: intrinsic motivators (facilitated by needs for
      autonomy, competency, and relatedness), extrinsic motivators (towards reward or
      away from punishment), or when intrinsic and extrinsic motivators are absent or
      thwarted a disconnect-disengagement occurs resulting in behavior driven by
      boredom or 'passing time'. Using a novel approach to Ecological Momentary
      Assessment, we assessed the degree to which people with schizophrenia were
      motivated by these factors relative to healthy control participants. Forty-seven
      people with and 41 people without schizophrenia were provided with cell phones
      and were called four times a day for one week. On each call participants were
      asked about their goals, and about the most important reason motivating each
      goal. All responses were coded by independent raters (blind to group and
      hypotheses) on all SDT motivating factors, and ratings were correlated to patient
      functioning and symptoms. We found that, relative to healthy participants, people
      with schizophrenia reported goals that were: (1) less motivated by filling
      autonomy and competency needs, but equivalently motivated by relatedness; (2)
      less extrinsically rewarding, but equivalently motivated by punishment; (3) more
      disconnected-disengaged. Higher disconnected-disengaged goals were significantly
      associated with higher negative symptoms and lower functioning. These findings
      indicate several important leverage points for behavioral treatments and suggest
      the need for vigorous psychosocial intervention focusing on autonomy, competence,
      and reward early in the course of illness.

PMID- 24853061
TI  - Cognitive performance and peripheral endocannabinoid system receptor expression
      in schizophrenia.
AB  - Schizophrenia is a chronic psychiatric syndrome characterized by generalized
      cognitive deficits that are associated with functional impairment. The
      endocannabinoid system (ECS) modulates neurotransmission and neuronal plasticity
      and is important for cognitive functioning. Evidence points to the involvement of
      this neuromodulatory system in the pathophysiology of schizophrenia and that
      alteration of the ECS on peripheral lymphocytes could reflect central changes.
      The objective of this study was to compare levels of peripheral endocannabinoid
      receptor expression in patients with schizophrenia and healthy subjects and find
      evidence of association between peripheral expression of those receptors and
      cognitive performance. Patients with stabilized schizophrenia (N=53) and controls
      (N=22) underwent clinical and cognitive evaluation, and assessment of cannabinoid
      receptor expression on the surface of peripheral immune cells (lymphocytes,
      natural killer cells and monocytes) by flow cytometry. Patients with
      schizophrenia had lower levels of cannabinoid receptor expression on total T
      lymphocytes, but after controlling for possible confounders this difference did
      not remain significant. In patients, increased cannabinoid receptor expression on
      lymphocytes and monocytes was significantly correlated with worst cognitive
      performance. These data provide additional evidence of the involvement of the ECS
      in the pathophysiology of cognitive deficits in schizophrenia. 

PMID- 24853062
TI  - Kenya Trypanosomiasis Research Institute cryobank for human and animal
      trypanosome isolates to support research: opportunities and challenges.

PMID- 24853063
TI  - Keeping them all together: beta-propeller domains in histone methyltransferase
      complexes.
AB  - Histone methyltransferases (HKMTs) residing in multi-subunit protein complexes
      frequently require the presence of beta-propeller proteins to achieve their
      biological functions. Recent biochemical studies have highlighted the functional
      diversity of these scaffolding proteins in maintaining the integrity of the
      complexes, allosterically regulating HKMT enzymatic activity and acting as
      "histone tethering devices" to facilitate the interaction between HKMTs and their
      substrates. Structural studies have revealed that, while beta-propeller domain
      proteins share structural similarity, they employ divergent mechanisms to achieve
      their functions. This review focuses on the progress made in the last decade to
      identify the biochemical determinants underlying the functions of these important
      proteins.

PMID- 24853064
TI  - Pediatric heart allocation and transplantation in Eurotransplant.
AB  - Pediatric heart allocation in Eurotransplant (ET) has evolved over the past
      decades to better serve patients and improve utilization. Pediatric heart
      transplants (HT) account for 6% of the annual transplant volume in ET. Death
      rates on the pediatric heart transplant waiting list have decreased over the
      years, from 25% in 1997 to 18% in 2011. Within the first year after listing, 32%
      of all infants (<12 months), 20% of all children aged 1-10 years, and 15% of all
      children aged 11-15 years died without having received a heart transplant.
      Survival after transplantation improved over the years, and in almost a decade,
      the 1-year survival went from 83% to 89%, and the 3-year rates increased from 81%
      to 85%. Improved medical management of heart failure patients and the
      availability of mechanical support for children have significantly improved the
      prospects for children on the heart transplant waiting list. 

PMID- 24853066
TI  - Sequencing of EHR adoption among US hospitals and the impact of meaningful use.
AB  - OBJECTIVE: To examine whether there is a common sequence of adoption of
      electronic health record (EHR) functions among US hospitals, identify differences
      by hospital type, and assess the impact of meaningful use. MATERIALS AND METHODS:
      Using 2008 American Hospital Association (AHA) Information Technology (IT)
      Supplement data, we calculate adoption rates of individual EHR functions, along
      with Loevinger homogeneity (H) coefficients, to assess the sequence of EHR
      adoption across hospitals. We compare adoption rates and Loevinger H coefficients
      for hospitals of different types to assess variation in sequencing. We
      qualitatively assess whether stage 1 meaningful use functions are those adopted
      early in the sequence. RESULTS: There is a common sequence of EHR adoption across
      hospitals, with moderate-to-strong homogeneity. Patient demographic and ancillary
      results functions are consistently adopted first, while physician notes, clinical
      reminders, and guidelines are adopted last. Small hospitals exhibited greater
      homogeneity than larger hospitals. Rural hospitals and non-teaching hospitals
      exhibited greater homogeneity than urban and teaching hospitals. EHR functions
      emphasized in stage 1 meaningful use are spread throughout the scale. DISCUSSION:
      Stronger homogeneity among small, rural, and non-teaching hospitals may be driven
      by greater reliance on vendors and less variation in the types of care they
      deliver. Stage 1 meaningful use is likely changing how hospitals sequence EHR
      adoption--in particular, by moving clinical guidelines and medication
      computerized provider order entry ahead in sequence. CONCLUSIONS: While there is
      a common sequence underlying adoption of EHR functions, the degree of adherence
      to the sequence varies by key hospital characteristics. Stage 1 meaningful use
      likely alters the sequence.

PMID- 24853065
TI  - mHealth interventions for weight loss: a guide for achieving treatment fidelity.
AB  - mHealth interventions have shown promise for helping people sustain healthy
      behaviors such as weight loss. However, few have assessed treatment fidelity,
      that is, the accurate delivery, receipt, and enactment of the intervention.
      Treatment fidelity is critical because the valid interpretation and translation
      of intervention studies depend on treatment fidelity assessments. We describe
      strategies used to assess treatment fidelity in mobile health (mHealth)
      interventions aimed at sustaining healthy behaviors in weight loss. We reviewed
      treatment fidelity recommendations for mHealth-based behavioral interventions and
      described how these recommendations were applied in three recent weight loss
      studies. We illustrate how treatment fidelity can be supported during study
      design, training of providers, treatment delivery, receipt of treatment, and
      enactment of treatment skills. Pre-planned strategies to ensure the treatment
      fidelity of mHealth interventions will help counter doubts concerning valid
      conclusions about their effectiveness and allow investigators and clinicians to
      implement robustly efficacious mobile health programs. TRIAL REGISTRATION NUMBER:
      1F31 NR012599.

PMID- 24853067
TI  - Supervised machine learning and active learning in classification of radiology
      reports.
AB  - OBJECTIVE: This paper presents an automated system for classifying the results of
      imaging examinations (CT, MRI, positron emission tomography) into reportable and
      non-reportable cancer cases. This system is part of an industrial-strength
      processing pipeline built to extract content from radiology reports for use in
      the Victorian Cancer Registry. MATERIALS AND METHODS: In addition to traditional
      supervised learning methods such as conditional random fields and support vector
      machines, active learning (AL) approaches were investigated to optimize training
      production and further improve classification performance. The project involved
      two pilot sites in Victoria, Australia (Lake Imaging (Ballarat) and Peter
      MacCallum Cancer Centre (Melbourne)) and, in collaboration with the NSW Central
      Registry, one pilot site at Westmead Hospital (Sydney). RESULTS: The
      reportability classifier performance achieved 98.25% sensitivity and 96.14%
      specificity on the cancer registry's held-out test set. Up to 92% of training
      data needed for supervised machine learning can be saved by AL. DISCUSSION: AL is
      a promising method for optimizing the supervised training production used in
      classification of radiology reports. When an AL strategy is applied during the
      data selection process, the cost of manual classification can be reduced
      significantly. CONCLUSIONS: The most important practical application of the
      reportability classifier is that it can dramatically reduce human effort in
      identifying relevant reports from the large imaging pool for further
      investigation of cancer. The classifier is built on a large real-world dataset
      and can achieve high performance in filtering relevant reports to support cancer
      registries.

PMID- 24853069
TI  - The changing geometry of a fitness landscape along an adaptive walk.
AB  - It has recently been noted that the relative prevalence of the various kinds of
      epistasis varies along an adaptive walk. This has been explained as a result of
      mean regression in NK model fitness landscapes. Here we show that this phenomenon
      occurs quite generally in fitness landscapes. We propose a simple and general
      explanation for this phenomenon, confirming the role of mean regression. We
      provide support for this explanation with simulations, and discuss the empirical
      relevance of our findings. 

PMID- 24853068
TI  - Programmed death 1 deficiency induces the polarization of macrophages/microglia
      to the M1 phenotype after spinal cord injury in mice.
AB  - The inflammatory response following spinal cord injury (SCI) involves the
      activation of resident microglia and the infiltration of macrophages. Macrophages
      and microglia can be polarized into the classically activated proinflammatory M1
      phenotype or the alternatively activated anti-inflammatory M2 phenotype.
      Programmed cell death 1 (PD-1) is a critical immune inhibitory receptor involved
      in innate and adaptive immune responses. However, whether PD-1 is involved in the
      modulation of macrophage/microglial polarization is unknown. In this study, the
      mRNA levels of pd1 gradually increased after SCI, and PD-1 protein was found in
      macrophages/microglia in injured spinal cord sections. PD-1 knockout (KO) mice
      showed poor locomotor recovery after spinal cord crushing compared with wild-type
      mice. M1-type macrophages/microglia accumulated in greater numbers in the injured
      spinal cord of PD-1-KO mice. Under polarized stimulation, induced expression of
      PD-1 occurred in cultured macrophages and microglia. PD-1 suppressed M1
      polarization by reducing the phosphorylation of signal transducer and activator
      of transcription 1 (STAT1) and promoted M2 polarization by increasing STAT6
      phosphorylation. In PD-1-KO mice, the M1 response was enhanced via the activation
      of STAT1 and nuclear factor-kappa B. Furthermore, PD-1 played various roles in
      phagocytosis in macrophages and microglia. Therefore, our results suggest that PD
      1 signaling plays an important role in the regulation of macrophage/microglial
      polarization. Thus, deregulated PD-1 signaling may induce the polarization of
      macrophages/microglia toward the M1 phenotype. Overall, our results provide new
      insights into the modulatory mechanisms of macrophage/microglial polarization,
      thereby possibly facilitating the development of new therapies for SCI via the
      regulation of macrophage/microglial polarization through PD-1 signaling. 

PMID- 24853070
TI  - Improved diagnosis of pulmonary emphysema using in vivo dark-field radiography.
AB  - OBJECTIVES: The purpose of this study was to assess whether the recently
      developed method of grating-based x-ray dark-field radiography can improve the
      diagnosis of pulmonary emphysema in vivo. MATERIALS AND METHODS: Pulmonary
      emphysema was induced in female C57BL/6N mice using endotracheal instillation of
      porcine pancreatic elastase and confirmed by in vivo pulmonary function tests,
      histopathology, and quantitative morphometry. The mice were anesthetized but
      breathing freely during imaging. Experiments were performed using a prototype
      small-animal x-ray dark-field scanner that was operated at 35 kilovolt (peak)
      with an exposure time of 5 seconds for each of the 10 grating steps. Images were
      compared visually. For quantitative comparison of signal characteristics, regions
      of interest were placed in the upper, middle, and lower zones of each lung.
      Receiver-operating-characteristic statistics were performed to compare the
      effectiveness of transmission and dark-field signal intensities and the combined
      parameter "normalized scatter" to differentiate between healthy and emphysematous
      lungs. RESULTS: A clear visual difference between healthy and emphysematous mice
      was found for the dark-field images. Quantitative measurements of x-ray dark
      field signal and normalized scatter were significantly different between the mice
      with pulmonary emphysema and the control mice and showed good agreement with
      pulmonary function tests and quantitative histology. The normalized scatter
      showed a significantly higher discriminatory power (area under the receiver
      operating-characteristic curve [AUC], 0.99) than dark-field (AUC, 0.90; P = 0.01)
      or transmission signal (AUC, 0.69; P < 0.001) alone did, allowing for an
      excellent discrimination of healthy and emphysematous lung regions. CONCLUSIONS:
      In a murine model, x-ray dark-field radiography is technically feasible in vivo
      and represents a substantial improvement over conventional transmission-based x
      ray imaging for the diagnosis of pulmonary emphysema.

PMID- 24853071
TI  - Dose and image quality of cone-beam computed tomography as compared with
      conventional multislice computed tomography in abdominal imaging.
AB  - OBJECTIVES: Recent technical developments have facilitated the application of
      cone-beam computed tomography (CBCT) for interventional and intraoperative
      imaging. The aim of this study was to compare the radiation doses and image
      quality in CBCT with those of conventional multislice spiral computed tomography
      (MSCT) for abdominal and genitourinary imaging. METHODS: Different CBCT and MSCT
      protocols for imaging soft tissues and hard-contrast objects at different dose
      levels were investigated in this study. Local skin and organ doses were measured
      with thermoluminescent dosimeters placed in an anthropomorphic phantom. Moreover,
      the contrast-to-noise ratio, the noise-power spectrum, and the high-contrast
      resolution derived from the modulation transfer function were determined in a
      phantom with the same absorption properties as those of anthropomorphic phantom.
      RESULTS: The effective dose of the examined abdominal/genitourinary CBCT
      protocols ranged between 0.35 mSv and 18.1 mSv. As compared with MSCT, the local
      skin dose of CBCT examinations could locally reach much higher doses up to 190
      mGy. The effective dose necessary to realize the same contrast-to-noise ratio
      with CBCT and MSCT depended on the MSCT convolution kernel: the MSCT dose was
      smaller than the corresponding CBCT dose for a soft kernel but higher than that
      for a hard kernel. The noise-power spectrum of the CBCT images at tube voltages
      of 85/90 kV(p) is at least half of that of images measured at 103/115 kV(p) at
      any arbitrarily chosen spatial frequency. Although the pixel size and slice
      thickness of CBCT were half of those of the MSCT images, high-contrast resolution
      was inferior to the MSCT images reconstructed with a hard convolution kernel.
      CONCLUSIONS: As compared with MSCT using a medium-hard convolution kernel, CBCT
      produces images at medium noise levels and, simultaneously, medium spatial
      resolution at approximately the same dose. It is well suited for visualizing hard
      contrast objects in the abdomen with relatively low image noise and patient dose.
      For the detection of low-contrast objects at standard tube voltages of
      approximately 120 kV(p), however, MSCT should be preferred.

PMID- 24853072
TI  - Wavelength-versatile graphene-gold film saturable absorber mirror for ultra
      broadband mode-locking of bulk lasers.
AB  - An ultra-broadband graphene-gold film saturable absorber mirror (GG-SAM) with a
      spectral coverage exceeding 1300 nm is experimentally demonstrated for mode
      locking of bulk solid-state lasers. Owing to the p-type doping effect caused by
      graphene-gold film interaction, the graphene on gold-film substrate shows a
      remarkably lower light absorption relative to pristine graphene, which is very
      helpful to achieve continuous-wave mode-locking in low-gain bulk lasers. Using
      the GG-SAM sample, stable mode-locking is realized in a Yb:YCOB bulk laser near 1
      MUm, a Tm:CLNGG bulk laser near 2 MUm and a Cr:ZnSe bulk laser near 2.4 MUm. The
      saturable absorption is characterised at an intermediate wavelength of 1.56 MUm
      by pump-probe measurements. The as-fabricated GG-SAM with ultra-broad bandwidth,
      ultrafast recovery time, low absorption, and low cost has great potential as a
      universal saturable absorber mirror for mode-locking of various bulk lasers with
      unprecedented spectral coverage. 

PMID- 24853073
TI  - Pan-digestive tract colonization by cytomegalovirus in common variable
      immunodeficiency.

PMID- 24853075
TI  - The Langmuir isotherm: a commonly applied but misleading approach for the
      analysis of protein adsorption behavior.
AB  - The Langmuir adsorption isotherm provides one of the simplest and most direct
      methods to quantify an adsorption process. Because isotherm data from protein
      adsorption studies often appear to be fit well by the Langmuir isotherm model,
      estimates of protein binding affinity have often been made from its use despite
      that fact that none of the conditions required for a Langmuir adsorption process
      may be satisfied for this type of application. The physical events that cause
      protein adsorption isotherms to often provide a Langmuir-shaped isotherm can be
      explained as being due to changes in adsorption-induced spreading, reorientation,
      clustering, and aggregation of the protein on a surface as a function of solution
      concentration in contrast to being due to a dynamic equilibrium adsorption
      process, which is required for Langmuir adsorption. Unless the requirements of
      the Langmuir adsorption process can be confirmed, fitting of the Langmuir model
      to protein adsorption isotherm data to obtain thermodynamic properties, such as
      the equilibrium constant for adsorption and adsorption free energy, may provide
      erroneous values that have little to do with the actual protein adsorption
      process, and should be avoided. In this article, a detailed analysis of the
      Langmuir isotherm model is presented along with a quantitative analysis of the
      level of error that can arise in derived parameters when the Langmuir isotherm is
      inappropriately applied to characterize a protein adsorption process.

PMID- 24853074
TI  - Atypical reversible posterior leukoencephalopathy syndrome (RPLS) induced by
      cediranib in a patient with metastatic rectal cancer.
AB  - BACKGROUND: Reversible posterior leukoenecphalopathy syndrome (RPLS) is a rare
      clinicoradiologic syndrome characterized by neurologic symptoms such as seizures,
      headaches, visual abnormalities, confusion and encephalopathy, accompanied by
      vasogenic edema of posterior white matter seen on neuroimaging. It has been
      reported in association with many anti-angiogenic therapies, including
      bevacizumab, sunitinib, sorafenib, pazopanib and regorafenib. Cediranib is a
      potent, orally available small molecule tyrosine kinase inhibitor with anti
      angiogenic activity, which has been shown to have activity against various solid
      tumors. CASE REPORT: We present a case of a 65 year old male with metastatic
      adenocarcinoma of the rectum who received cediranib as part of a phase I clinical
      trial. He developed confusion and fluctuations in his level of consciousness. MRI
      of the brain revealed diffuse low level T2 signal abnormality in the cerebral
      peduncles, pons, and medulla and patchy T2 signal in both thalami, consistent
      with RPLS. With conservative management, including tight blood pressure control,
      his symptoms improved and MRI findings resolved. CONCLUSION: RPLS is a rare, but
      serious, clinicoradiologic syndrome which has been described as an adverse effect
      of many anti-angiogenic agents and should also be considered in patients on
      cediranib who present with neurologic symptoms along with vasogenic edema seen on
      MRI. If RPLS is suspected, cediranib should be discontinued and blood pressure
      should be aggressively controlled.

PMID- 24853076
TI  - Helicobacter hepaticus cholesterol-alpha-glucosyltransferase is essential for
      establishing colonization in male A/JCr mice.
AB  - BACKGROUND: Helicobacter pylori cholesterol-alpha-glucosyltransferase (cgt) is
      essential for survival of H. pylori in mice. Enterohepatic H. hepaticus, the
      cause of colonic and hepatocellular carcinoma in susceptible mouse strains,
      contains an ortholog of the H. pylori cgt. However, the role of cgt in the
      pathogenesis of H. hepaticus has not been investigated. MATERIALS AND METHODS:
      Two cgt-deficient isogenic mutants of wild-type H. hepaticus (WT) 3B1 were
      generated and used to inoculate male A/JCr mice. Cecal and hepatic colonization
      levels of the mutants and WT 3B1 as well as select inflammation-associated
      cytokines were measured by qPCR at 4 months postinoculation. RESULTS: Both
      mutants were undetectable in the cecum of any inoculated mice (10 per mutant) but
      were detected in two livers (one for each mutant); by contrast, 9 and 7 of 10
      mice inoculated with WT 3B1 were qPCR positive in the ceca and livers,
      respectively. The mice inoculated with the mutants developed significantly less
      severe hepatic inflammation (p < .05) and also produced significantly lower
      hepatic mRNA levels of proinflammatory cytokines Ifn-gamma (p < .01) and Tnf
      alpha (p <= .02) as well as anti-inflammatory factors Il10 and Foxp3 compared
      with the WT 3B1-inoculated mice. Additionally, the WT 3B1-inoculated mice
      developed significantly higher Th1-associated IgG2a (p < .0001) and Th2
      associated IgG1 responses (p < .0001) to H. hepaticus infection than mice dosed
      with isogenic cgt mutants. CONCLUSION: Our data indicate that the cholesterol
      alpha-glucosyltransferase is required for establishing colonization of the
      intestine and liver and therefore plays a critical role in the pathogenesis of H.
      hepaticus.

PMID- 24853078
TI  - Commercial motorcycle drivers' perceptions of risk and road safety in urban
      Nigeria: an explorative study.
AB  - Road traffic injury is a great public health challenge with an emerging trend of
      increasing rates and high mortality involving commercial motorcycles in Nigeria.
      A qualitative approach was used with 10 in-depth interviews conducted to explore
      the risk perceptions of commercial motorcyclists in Ibadan, Nigeria. The data
      analysis using manifest and latent content analysis resulted in an overarching
      theme: inadequate structures and internalised norms prevent change. The three
      themes leading to the overarching theme are: risk-taking as generally acceptable;
      risk-taking as an intrinsic part of occupation; and risk-taking as a way to make
      ends meet. The study suggests that there is a great need for adequate regulation
      as regards training and licensing of riders. Also the need to tighten enforcement
      of traffic rules is paramount to road safety in Nigeria.

PMID- 24853077
TI  - Dynamic transcription factor activity profiles reveal key regulatory interactions
      during megakaryocytic and erythroid differentiation.
AB  - The directed differentiation toward erythroid (E) or megakaryocytic (MK) lineages
      by the MK-E progenitor (MEP) could enhance the ex vivo generation of red blood
      cells and platelets for therapeutic transfusions. The lineage choice at the MEP
      bifurcation is controlled in large part by activity within the intracellular
      signal transduction network, the output of which determines the activity of
      transcription factors (TFs) and ultimately gene expression. Although many TFs
      have been implicated, E or MK differentiation is a complex process requiring
      multiple days, and the dynamics of TF activities during commitment and terminal
      maturation are relatively unexplored. Herein, we applied a living cell array for
      the large-scale, dynamic quantification of TF activities during MEP bifurcation.
      A panel of hematopoietic TFs (GATA-1, GATA-2, SCL/TAL1, FLI-1, NF-E2, PU.1, c
      Myb) was characterized during E and MK differentiation of bipotent K562 cells.
      Dynamic TF activity profiles associated with differentiation towards each lineage
      were identified, and validated with previous reports. From these activity
      profiles, we show that GATA-1 is an important hub during early hemin- and PMA
      induced differentiation, and reveal several characteristic TF interactions for E
      and MK differentiation that confirm regulatory mechanisms documented in the
      literature. Additionally, we highlight several novel TF interactions at various
      stages of E and MK differentiation. Furthermore, we investigated the mechanism by
      which nicotinamide (NIC) promoted terminal MK maturation using an MK-committed
      cell line, CHRF-288-11 (CHRF). Concomitant with its enhancement of ploidy, NIC
      strongly enhanced the activity of three TFs with known involvement in terminal MK
      maturation: FLI-1, NF-E2, and p53. Dynamic profiling of TF activity represents a
      novel tool to complement traditional assays focused on mRNA and protein
      expression levels to understand progenitor cell differentiation.

PMID- 24853079
TI  - Genomics of wood-degrading fungi.
AB  - Woody plants convert the energy of the sun into lignocellulosic biomass, which is
      an abundant substrate for bioenergy production. Fungi, especially wood decayers
      from the class Agaricomycetes, have evolved ways to degrade lignocellulose into
      its monomeric constituents, and understanding this process may facilitate the
      development of biofuels. Over the past decade genomics has become a powerful tool
      to study the Agaricomycetes. In 2004 the first sequenced genome of the white rot
      fungus Phanerochaete chrysosporium revealed a rich catalog of lignocellulolytic
      enzymes. In the decade that followed the number of genomes of Agaricomycetes grew
      to more than 75 and revealed a diversity of wood-decaying strategies. New
      technologies for high-throughput functional genomics are now needed to further
      study these organisms. 

PMID- 24853081
TI  - Modeling age-specific mortality for countries with generalized HIV epidemics.
AB  - BACKGROUND: In a given population the age pattern of mortality is an important
      determinant of total number of deaths, age structure, and through effects on age
      structure, the number of births and thereby growth. Good mortality models exist
      for most populations except those experiencing generalized HIV epidemics and some
      developing country populations. The large number of deaths concentrated at very
      young and adult ages in HIV-affected populations produce a unique 'humped' age
      pattern of mortality that is not reproduced by any existing mortality models.
      Both burden of disease reporting and population projection methods require age
      specific mortality rates to estimate numbers of deaths and produce plausible age
      structures. For countries with generalized HIV epidemics these estimates should
      take into account the future trajectory of HIV prevalence and its effects on age
      specific mortality. In this paper we present a parsimonious model of age-specific
      mortality for countries with generalized HIV/AIDS epidemics. METHODS AND
      FINDINGS: The model represents a vector of age-specific mortality rates as the
      weighted sum of three independent age-varying components. We derive the age
      varying components from a Singular Value Decomposition of the matrix of age
      specific mortality rate schedules. The weights are modeled as a function of HIV
      prevalence and one of three possible sets of inputs: life expectancy at birth, a
      measure of child mortality, or child mortality with a measure of adult mortality.
      We calibrate the model with 320 five-year life tables for each sex from the World
      Population Prospects 2010 revision that come from the 40 countries of the world
      that have and are experiencing a generalized HIV epidemic. Cross validation shows
      that the model is able to outperform several existing model life table systems.
      CONCLUSIONS: We present a flexible, parsimonious model of age-specific mortality
      for countries with generalized HIV epidemics. Combined with the outputs of
      existing epidemiological and demographic models, this model makes it possible to
      project future age-specific mortality profiles and number of deaths for countries
      with generalized HIV epidemics.

PMID- 24853082
TI  - Quantum dot and superparamagnetic nanoparticle interaction with pathogenic fungi:
      internalization and toxicity profile.
AB  - For several years now, nanoscaled materials have been implemented in
      biotechnological applications related to animal (in particular human) cells and
      related pathologies. However, the use of nanomaterials in plant biology is far
      less widespread, although their application in this field could lead to the
      future development of plant biotechnology applications. For any practical use, it
      is crucial to elucidate the relationship between the nanomaterials and the target
      cells. In this work we have evaluated the behavior of two types of nanomaterials,
      quantum dots and superparamagnetic nanoparticles, on Fusarium oxysporum, a fungal
      species that infects an enormous range of crops causing important economic losses
      and is also an opportunistic human pathogen. Our results indicated that both
      nanomaterials rapidly interacted with the fungal hypha labeling the presence of
      the pathogenic fungus, although they showed differential behavior with respect to
      internalization. Thus, whereas magnetic nanoparticles appeared to be on the cell
      surface, quantum dots were significantly taken up by the fungal hyphae showing
      their potential for the development of novel control approaches of F. oxysporum
      and related pathogenic fungi following appropriate functionalization. In
      addition, the fungal germination and growth, accumulation of ROS, indicative of
      cell stress, and fungal viability have been evaluated at different nanomaterial
      concentrations showing the low toxicity of both types of nanomaterials to the
      fungus. This work represents the first study on the behavior of quantum dots and
      superparamagnetic particles on fungal cells, and constitutes the first and
      essential step to address the feasibility of new nanotechnology-based systems for
      early detection and eventual control of pathogenic fungi. 

PMID- 24853080
TI  - A critique of the drug discovery and phase 3 clinical programs targeting the
      amyloid hypothesis for Alzheimer disease.

PMID- 24853083
TI  - Prognostic implications of quantitative evaluation of baseline Q-wave width in ST
      segment elevation myocardial infarction.
AB  - OBJECTIVES: To evaluate quantitative relationships between baseline Q-wave width
      and 90-day outcomes in ST-segment elevation myocardial infarction (STEMI).
      BACKGROUND: Baseline Q-waves are useful in predicting clinical outcomes after MI.
      METHODS: 3589 STEMI patients were assessed from a multi-centre study. RESULTS:
      1156 patients of the overall cohort had pathologic Q-waves. The 90-day mortality
      and the composite of mortality, congestive heart failure (CHF), or cardiogenic
      shock (p<0.001 for both outcomes) rose as Q-wave width increased. After adapting
      a threshold >=40ms for inferior and >=20ms for lateral/apical MI in all patients
      (n=3065) with any measureable Q-wave we found hazard ratios (HR) for mortality
      (HR: 2.44, 95% confidence interval (CI) (1.54-3.85), p<0.001) and the composite
      (HR: 2.32, 95% CI (1.70-3.16), p<0.001). This improved reclassification of
      patients experiencing the composite endpoint versus the conventional definition
      (net reclassification index (NRI): 0.23, 95% CI (0.09-0.36), p<0.001) and
      universal MI definition (NRI: 0.15, 95% CI (0.02-0.29), p=0.027). CONCLUSIONS:
      The width of the baseline Q-wave in STEMI adds prognostic value in predicting 90
      day clinical outcomes. A threshold of >=40ms in inferior and >=20ms for
      lateral/apical MI enhances prognostic insight beyond current criteria.

PMID- 24853084
TI  - Use of electrocardiogram indices of myocardial ischemia for risk stratification
      and decision making of reperfusion strategies.
AB  - After about a century since its clinical introduction, the 12-lead
      electrocardiogram (ECG) remains a cornerstone in diagnosis and management of
      acute ST-elevation myocardial infarction (STEMI). It provides clinicians and
      researchers with invaluable information regarding the presence, location, and
      extent of myocardial infarction. Moreover the ECG contains a wealth of prognostic
      information useful in risk stratification of STEMI patients and identification of
      particular subgroups that may benefit from more aggressive therapeutic
      interventions. New data suggest the ECG may be useful in guiding the choice of
      reperfusion treatment when primary percutaneous coronary intervention (PCI)
      cannot be delivered in the timeframe recommended by current STEMI guidelines.
      This paper summarizes the role of the ECG in assessing the baseline risk of
      patients with STEMI and evaluates the use of ECG indices in decision making of
      reperfusion strategies.

PMID- 24853085
TI  - Evaluation of very low amplitude intra-QRS potentials during the initial minutes
      of acute transmural myocardial ischemia.
AB  - INTRODUCTION: Low-level electrocardiographic changes from depolarization
      wavefront may accompany acute myocardial ischemia. The purpose of this study was
      to assess the changes of microvolt amplitude intra-QRS potentials induced by
      elective percutaneous coronary interventions (PCI). METHODS: Fifty-seven patients
      with balloon inflation periods ranging from 3.1 to 7.3 minutes (4.9+/-0.7 min)
      were studied. Nine leads continuous high-resolution ECG before and during PCI
      were recorded and signal-averaged. Abnormal intra-QRS at microvolt level (MUAIQP)
      were obtained using a signal modeling approach. MUAIQP, R-wave amplitude and QRS
      duration were measured in the processed ECG during baseline and PCI episodes.
      RESULTS: The mean MUAIQP amplitude significantly decreased for each of the
      standard 12 leads at the PCI event respect to baseline. Left anterior descending
      artery (LAD) occlusion resulted in a decrease MUAIQP in both the precordial leads
      and the limb leads, while right coronary (RCA) and left circumflex (LCx) arteries
      occlusions mainly affected limb leads. R-wave amplitude increased during PCI in
      RCA and LCx groups in lead III but decreased in the precordial leads, while the
      amplitude decreased in the LAD group in lead III. The average duration of the QRS
      augmented in groups RCA and LCx but not in the LAD group. CONCLUSIONS: Abnormal
      intra-QRS potentials at the level of MUV provide an excellent tool to
      characterize the very-low amplitude fragmentation of the QRS complex and its
      changes due to ischemic injuries. MUAIQP shows promise as a new ECG index to
      measure electrophysiologic changes associated with acute myocardial ischemia.

PMID- 24853086
TI  - Chromosome aberrations identified by cytogenetic analysis of the first two clones
      of cultured amniotic fluid cells compared with QF-PCR results.
AB  - We report on our experience of studying amniotic fluid cells by cytogenetic
      analysis (CA) of the first 2 clones. We investigated the incidence and types of
      chromosome aberrations detected by CA of 196 amniocenteses performed on pregnant
      women at high risk. Of these cases, 178 were analysed by QF-PCR (risk group A).
      The results were compared with the data obtained by CA of 1,263 amniocenteses
      carried out in patients with other indications. QF-PCR was used to investigate
      1,030 of these cases (risk group B). The combined average turnaround time for a
      CA result of the first 2 clones in both risk groups was within 9 +/- 2 days. The
      final CA results (>=6 clones) were obtained within 12 +/- 4 days. In risk group
      A, CA was not possible in 2 cases due to cell culture failure. The foetal
      karyotype was abnormal in 13.8% of the cases by CA of >=6 clones and in 13.5% of
      the cases by QF-PCR. Together, CA of >=6 clones and QF-PCR detected chromosome
      aberrations in 14.8% of the cases. With the exception of 2 cases of in vitro
      culture failure and 1 case with low gonosomal mosaicism, CA of the first 2 clones
      detected all cases with chromosome aberrations. Five cases with clinically
      significant chromosome aberrations were not detected by QF-PCR. In risk group B,
      the foetal karyotype was found to be abnormal in 2.2% of the cases by CA of >=6
      clones and in 1.0% of the cases by QF-PCR. Together, CA of >=6 clones and QF-PCR
      revealed chromosome aberrations in 2.2% of the cases. With the exception of 1
      case with low gonosomal mosaicism, CA of the first 2 clones detected all other
      cases with chromosome aberrations. The majority of these cases were inherited
      chromosome aberrations. Eighteen cases with chromosome aberrations were not
      detected by QF-PCR. Based on our results, CA of >=6 clones, together with QF-PCR
      as a first test, should be performed in all prenatal cases with abnormal
      ultrasound findings. In pregnancies with other indications, CA of the first 2
      clones alone is sufficient to identify all clinically significant (and inherited)
      chromosome aberrations.

PMID- 24853087
TI  - Effects of early blood pressure lowering on early and long-term outcomes after
      acute stroke: an updated meta-analysis.
AB  - BACKGROUND: Hypertension is common after acute stroke onset. Previous studies
      showed controversial effects of early blood pressure (BP) lowering on stroke
      outcomes. The aim of this study is to assess the effects of early BP lowering on
      early and long-term outcomes after acute stroke. METHODS: A meta-analysis was
      conducted with prospective randomized controlled trials assessing the effects of
      early BP lowering on early and long-term outcomes after acute stroke compared
      with placebo. Literature searching was performed in the databases from inception
      to December 2013. New evidence from recent trials were included. Outcomes were
      analyzed as early (within 30 days) and long-term (from 3 to 12 months) endpoints
      using summary estimates of relative risks (RR) and their 95% confidence intervals
      (CI) with the fixed-effect model or random-effect model. RESULTS: Seventeen
      trials providing data from 13236 patients were included. Pooled results showed
      that early BP lowering after acute stroke onset was associated with more death
      within 30 days compared with placebo (RR: 1.34 and 95% CI: 1.02, 1.74, p = 0.03).
      However the results showed that early BP lowering had no evident effect on early
      neurological deterioration, early death within 7 days, long-term death, early and
      long-term dependency, early and long-term combination of death or dependency,
      long-term stroke recurrence, long-term myocardial infarction and long-term CVE.
      CONCLUSIONS: The new results lend no support to early BP lowering after acute
      stroke. Early BP lowering may increase death within 30 days after acute stroke.

PMID- 24853088
TI  - Late onset of the serological response against the 18 kDa small heat shock
      protein of Mycobacterium ulcerans in children.
AB  - A previous survey for clinical cases of Buruli ulcer (BU) in the Mape Basin of
      Cameroon suggested that, compared to older age groups, very young children may be
      less exposed to Mycobacterium ulcerans. Here we determined serum IgG titres
      against the 18 kDa small heat shock protein (shsp) of M. ulcerans in 875
      individuals living in the BU endemic river basins of the Mape in Cameroon and the
      Densu in Ghana. While none of the sera collected from children below the age of
      four contained significant amounts of 18 kDa shsp specific antibodies, the
      majority of sera had high IgG titres against the Plasmodium falciparum merozoite
      surface protein 1 (MSP-1). These data suggest that exposure to M. ulcerans
      increases at an age which coincides with the children moving further away from
      their homes and having more intense environmental contact, including exposure to
      water bodies at the periphery of their villages. 

PMID- 24853090
TI  - Coal seam gas water: potential hazards and exposure pathways in Queensland.
AB  - The extraction of coal seam gas (CSG) produces large volumes of potentially
      contaminated water. It has raised concerns about the environmental health impacts
      of the co-produced CSG water. In this paper, we review CSG water contaminants and
      their potential health effects in the context of exposure pathways in
      Queensland's CSG basins. The hazardous substances associated with CSG water in
      Queensland include fluoride, boron, lead and benzene. The exposure pathways for
      CSG water are (1) water used for municipal purposes; (2) recreational water
      activities in rivers; (3) occupational exposures; (4) water extracted from
      contaminated aquifers; and (5) indirect exposure through the food chain. We
      recommend mapping of exposure pathways into communities in CSG regions to
      determine the potentially exposed populations in Queensland. Future efforts to
      monitor chemicals of concern and consolidate them into a central database will
      build the necessary capability to undertake a much needed environmental health
      impact assessment. 

PMID- 24853089
TI  - Development of SLE among "potential SLE" patients seen in consultation: long-term
      follow-up.
AB  - OBJECTIVE: To identify factors associated with development of systemic lupus
      erythematosus (SLE) among patients evaluated at a tertiary care Lupus Center for
      potential SLE. METHODS: We identified patients first seen at the Brigham and
      Women's Hospital Lupus Center between 1 January 1992 and 31 December 2012 and
      thought to have potential SLE by a board-certified rheumatologist. All had 1-3
      SLE ACR criteria at initial visit and > 2 follow-up visits >= 3 months apart. We
      reviewed medical records through 15 May 2013 for: SLE signs and symptoms,
      autoimmune serologies, prescriptions and diagnoses by board-certified
      rheumatologists. Bivariable analyses and multivariable logistic regression models
      were used to identify independent predictors of developing SLE. RESULTS: Two
      hundred and sixty four patients met inclusion criteria. At initial visit, mean
      age was 39.2 (SD 12.4) years, 94% were female and 67% white. Mean number of SLE
      ACR criteria was 2.7 (SD 1.0) and 88% were antinuclear antibody (ANA) positive at
      initial consultation. Mean follow-up time was 6.3 (SD 4.3) years and 67% were
      prescribed hydroxychloroquine in follow-up. At most recent visit, 56 (21%) had
      been diagnosed with SLE; 47 (18%) were thought not to have SLE and 161 (61%) were
      still considered to have potential SLE. In multivariable regression models, oral
      ulcers (OR 2.40, 95% CI 1.03-5.58), anti-dsDNA (OR 2.59, 95% CI 1.25-5.35) and
      baseline proteinuria or cellular casts (OR 16.20, 95% CI 1.63-161.02) were
      independent predictors of developing SLE. The most common other final diagnoses
      included fibromyalgia, Sjogren's syndrome, mixed connective tissue disease and
      cutaneous lupus. CONCLUSION: Among patients with potential SLE at initial
      consultation, 21% were diagnosed with definite SLE within 6.3 years. Oral ulcers,
      anti-dsDNA and proteinuria or cellular casts were independent predictors of
      developing definite SLE. A better means of accurately identifying those who will
      develop SLE among those presenting with potential disease is necessary.

PMID- 24853091
TI  - Larval behaviours and their contribution to the distribution of the intertidal
      coral reef sponge Carteriospongia foliascens.
AB  - Sponges (Phylum Porifera) are an evolutionary and ecologically significant group;
      however information on processes influencing sponge population distributions is
      surprisingly limited. Carteriospongia foliascens is a common Indo-Pacific sponge,
      which has been reported from the intertidal to the mesophotic. Interestingly, the
      distribution of C. foliascens at inshore reefs of the Great Barrier Reef is
      restricted to the intertidal with no individuals evident in adjacent subtidal
      habitats. The abundance of C. foliascens and substrate availability was first
      quantified to investigate the influence of substrate limitation on adult
      distribution. Pre-settlement processes of larval spawning, swimming speeds,
      phototaxis, vertical migration, and settlement to intertidal and subtidal
      substrate cues were also quantified. Notably, suitable settlement substrate
      (coral rubble) was not limiting in subtidal habitats. C. foliascens released up
      to 765 brooded larvae sponge(-1) day(-1) during the day, with larvae (80%+/-5.77)
      being negatively phototactic and migrating to the bottom within 40 minutes from
      release. Subsequently, larvae (up to 58.67%+/-2.91) migrated to the surface after
      the loss of the daylight cue (nightfall), and after 34 h post-release >98.67% (+/
      0.67) of larvae had adopted a benthic habit regardless of light conditions.
      Intertidal and subtidal biofilms initiated similar settlement responses, inducing
      faster (as early 6 h post-release) and more successful metamorphosis (>60%) than
      unconditioned surfaces. C. foliascens has a high larval supply and larval
      behaviours that support recruitment to the subtidal. The absence of C. foliascens
      in subtidal habitats at inshore reefs is therefore proposed to be a potential
      consequence of post-settlement mortalities.

PMID- 24853092
TI  - BSA Au clusters as a probe for enhanced fluorescence detection using multipulse
      excitation scheme.
AB  - Although BSA Au clusters fluoresce in red region (lambdamax: 650 nm), they are of
      limited use due to low fluorescence quantum yield (~6%). Here we report an
      enhanced fluorescence imaging application of fluorescent bio-nano probe BSA Au
      clusters using multipulse excitation scheme. Multipulse excitation takes
      advantage of long fluorescence lifetime (> 1 us) of BSA Au clusters and enhances
      its fluorescence intensity 15 times over short lived cellular auto-fluorescence.
      Moreover we have also shown that by using time gated detection strategy signal
      (fluorescence of BSA Au clusters) to noise (auto-fluorescence) ratio can be
      increased by 30 fold. Thereby with multipulse excitation long lifetime probes can
      be used to develop biochemical assays and perform optical imaging with zero
      background.

PMID- 24853094
TI  - Comparative efficacy and safety of different doses of ergocalciferol
      supplementation in patients with metabolic syndrome.
AB  - BACKGROUND: Vitamin D deficiency is a common problem worldwide. Several studies
      have shown an association between vitamin D deficiency and the increased risk of
      metabolic syndrome. No previous study has compared the efficacy and safety of
      ergocalciferol at 40,000 versus 20,000 IU/week in patients with metabolic
      syndrome. OBJECTIVE: To evaluate the efficacy of ergocalciferol supplementation
      on serum 25-hydroxyvitamin D [25(OH)D] concentrations and to examine safety
      parameters in metabolic syndrome patients. SETTING: Outpatient department of
      Phramongkutklao Hospital, Bangkok, Thailand. METHOD: A randomized, double
      blinded, parallel study was conducted in metabolic syndrome patients with vitamin
      D deficiency [25(OH)D <20 ng/mL]. Ninety patients were randomly assigned into
      three groups of 30 patients each. Group 1 was given two capsules of placebo/week,
      group 2 was given ergocalciferol 20,000 IU/week, and group 3 was given
      ergocalciferol 40,000 IU/week for 8 weeks. MAIN OUTCOME MEASURE: serum 25(OH)D
      concentrations, serum calcium, safety, and corrected QT (QTc) interval. RESULTS:
      Of the 90 patients enrolled, 84 patients completed the study. At the end of the
      study, the mean serum 25(OH)D in groups 2 and 3 significantly increased from the
      baseline (15.1 and 14.3 to 26.8 and 30.0 ng/mL, respectively). The increase in
      serum 25(OH)D in groups 2 and 3 were comparable and significantly greater than
      that of the placebo group. The percentage number of patients achieving normal
      vitamin D levels in groups 1, 2 and 3 were 3.3, 33.3, and 60.0 %, respectively,
      which were significantly different between groups (p < 0.001). Adverse reactions
      in both ergocalciferol treatment groups were not different from the placebo group
      (p > 0.05). Serum calcium levels did not change within and between groups of
      treatment. No significant change in QTc was observed in any patient. CONCLUSIONS:
      Both 20,000 and 40,000 IU/week of ergocalciferol supplementation for 8 weeks were
      able to increase serum 25(OH)D concentrations significantly. However, more
      patients in the ergocalciferol 40,000 IU/week treatment group achieved a normal
      serum 25(OH)D level than in the group which received 20,000 IU/week. Clinicians
      would have informed of choosing the dosing regimen of ergocalciferol in metabolic
      syndrome patients.

PMID- 24853095
TI  - Serum bacterial toxins are related to the progression of inflammatory bowel
      disease.
AB  - OBJECTIVES: Inflammatory bowel disease (IBD), including Crohn's disease (CD) and
      ulcerative colitis (UC), is an autoimmune disease. Disorder of intestinal
      microbes is thought to play a critical role in the pathogenesis of IBD. Detection
      of bacterial toxins could become a new approach to judge the situation of this
      disease. MATERIALS AND METHODS: Serum samples were collected from 142 IBD
      patients and 40 healthy donors as well as 15 CD patients with anti-tumor necrosis
      factor (TNF) monoclonal antibody (infliximab [IFX]). Enzyme-linked immunosorbent
      assay kits for Clostridium difficile, Escherichia coli O157, salmonella, and
      Staphylococcus aureus were used to analyze these bacterial toxins in sera.
      RESULTS: The positive rates of bacterial toxins from C. difficile, E. coli O157,
      salmonella, and S. aureus in the IBD patients were found in low incidences and
      associated with disease duration, colonic involvement, and treatment with
      prednisone and immunomodulators. The active CD and UC patients had significant
      higher positive rates of these bacterial toxins than those in remission or
      healthy controls. Blockage of TNF with IFX in CD patients resulted in significant
      decreases of the levels of toxins of C. difficile, E. coli O157, salmonella, and
      S. aureus in sera. CONCLUSIONS: Some bacterial toxins are present in the sera of
      active IBD patients, and patients with long disease duration, colonic
      involvement, or treatment with prednisone and immunomodulators are more
      susceptible to bacterial infection. Inhibition of inflammation with IFX would
      reduce the bacterial toxins via improvement of intestinal inflammation. Detecting
      bacteria-derived toxins in sera can be used to predict the progression of IBD.

PMID- 24853093
TI  - Identification of nitric oxide as an endogenous inhibitor of 26S proteasomes in
      vascular endothelial cells.
AB  - The 26S proteasome plays a fundamental role in almost all eukaryotic cells,
      including vascular endothelial cells. However, it remains largely unknown how
      proteasome functionality is regulated in the vasculature. Endothelial nitric
      oxide (NO) synthase (eNOS)-derived NO is known to be essential to maintain
      endothelial homeostasis. The aim of the present study was to establish the
      connection between endothelial NO and 26S proteasome functionality in vascular
      endothelial cells. The 26S proteasome reporter protein levels, 26S proteasome
      activity, and the O-GlcNAcylation of Rpt2, a key subunit of the proteasome
      regulatory complex, were assayed in 26S proteasome reporter cells, human
      umbilical vein endothelial cells (HUVEC), and mouse aortic tissues isolated from
      26S proteasome reporter and eNOS knockout mice. Like the other selective NO
      donors, NO derived from activated eNOS (by pharmacological and genetic approach)
      increased O-GlcNAc modification of Rpt2, reduced proteasome chymotrypsin-like
      activity, and caused 26S proteasome reporter protein accumulation. Conversely,
      inactivation of eNOS reversed all the effects. SiRNA knockdown of O-GlcNAc
      transferase (OGT), the key enzyme that catalyzes protein O-GlcNAcylation,
      abolished NO-induced effects. Consistently, adenoviral overexpression of O
      GlcNAcase (OGA), the enzyme catalyzing the removal of the O-GlcNAc group,
      mimicked the effects of OGT knockdown. Finally, compared to eNOS wild type aortic
      tissues, 26S proteasome reporter mice lacking eNOS exhibited elevated 26S
      proteasome functionality in parallel with decreased Rpt2 O-GlcNAcylation, without
      changing the levels of Rpt2 protein. In conclusion, the eNOS-derived NO functions
      as a physiological suppressor of the 26S proteasome in vascular endothelial
      cells. 

PMID- 24853096
TI  - Parasite load decrease during application of a safe and easily applied
      antileishmanial aminoglycoside cream.

PMID- 24853097
TI  - Reversible pulmonary arterial hypertension in cobalamin-dependent cobalamin C
      disease due to a novel mutation in the MMACHC gene.
AB  - Methylmalonic aciduria and homocystinuria, cobalamin C (CblC) disease (OMIM
      277400), is the most frequent inborn error of vitamin B12 (cobalamin, Cbl)
      metabolism and is caused by an inability of the cell to convert Cbl to its active
      forms (MeCbl and AdoCbl). More than 75 mutations have been identified in the
      MMACHC gene which is responsible for CblC disease. We present a case with CblC
      disease and pulmonary arterial hypertension (PAH) as the main symptom. The
      patient improved dramatically with parenteral hydroxocobalamin treatment. Most
      cases of CblC disease have a multisystemic disease with failure to thrive,
      developmental delay, hypotonia, visual impairment, and hematologic
      manifestations. This patient had isolated pulmonary hypertension and
      hyperhomocysteinemia which is thought to be an important factor in the
      pathogenesis of PAH. Genetic analysis identified a novel homozygous mutation
      (c.484G > T; p.Gly162Trp) in the MMACHC gene. CONCLUSION: CblC disease should be
      considered in the differential diagnosis of pulmonary hypertension.

PMID- 24853098
TI  - Optimism as a prior belief about the probability of future reward.
AB  - Optimists hold positive a priori beliefs about the future. In Bayesian
      statistical theory, a priori beliefs can be overcome by experience. However,
      optimistic beliefs can at times appear surprisingly resistant to evidence,
      suggesting that optimism might also influence how new information is selected and
      learned. Here, we use a novel Pavlovian conditioning task, embedded in a
      normative framework, to directly assess how trait optimism, as classically
      measured using self-report questionnaires, influences choices between visual
      targets, by learning about their association with reward progresses. We find that
      trait optimism relates to an a priori belief about the likelihood of rewards, but
      not losses, in our task. Critically, this positive belief behaves like a
      probabilistic prior, i.e. its influence reduces with increasing experience.
      Contrary to findings in the literature related to unrealistic optimism and self
      beliefs, it does not appear to influence the iterative learning process directly.

PMID- 24853099
TI  - Reduced membranous MET expression is linked to bladder cancer progression.
AB  - The MET protein is involved in the malignant progression of different tumors.
      This study aimed to analyze the relationship of MET expression with tumor
      phenotype and clinical outcome in bladder cancer and the role of gene
      amplification for MET overexpression. A bladder cancer tissue microarray
      containing 686 bladder cancers was analyzed by immunohistochemistry and by
      fluorescence in situ hybridization. MET immunostaining was seen in normal
      urothelium and was recorded in 459 of 560 analyzable urothelial carcinomas
      (82.0%). Low MET staining was associated with a more unfavorable tumor phenotype.
      MET staining was seen in 89.8% of 266 pTa, 81.1% of 132 pT1, and 69.4% of 160 pT2
      4 cancers (P < 0.0001). MET staining was detectable in 92.4% of 66 grade 1, 85.6%
      of 257 grade 2, and 75.1% of 237 grade 3 cancers (P = 0.001). MET expression
      status was not associated with overall or tumor-specific survival in muscle
      invasive cancers (pT2-4), tumor progression in pT1 cancers, or recurrences in pTa
      tumors. Only four of the analyzed tumors (0.8%) showed amplification of the MET
      gene. We conclude that MET is not overexpressed in urothelial cancer but rather
      downregulated in a fraction of cancers. Accordingly, rare amplification of the
      genomic area including the MET gene was not associated with MET protein
      overexpression. 

PMID- 24853100
TI  - Genetic anticipation of familial breast cancer with or without BRCA mutation in
      the Korean population.
AB  - We investigated genetic anticipation of breast or ovarian cancer in patients with
      familial breast cancer. Among 201 patients with breast cancer who had a family
      history of breast or ovarian cancer, 95 families had affected familial members in
      the previous generation. Of these families, 2 were excluded because of
      insufficient data. From the 93 eligible families, 112 and 111 members were
      identified in the previous and proband generations, respectively. BRCA mutations
      were detected in 26 (28.0%) of the 93 probands. The median age at diagnosis of
      the first generation was 57 years and of the second generation was 40 years,
      which was a significant difference. The result from the mixed-effects model also
      demonstrated significant genetic anticipation (P < 0.0001). The expected age
      difference at onset of breast or ovarian cancer between the two generations was
      17.06 years. BRCA mutation status did not influence the generational difference
      in age at diagnosis (17.99 vs. 16.62 y, P = 0.3973). Genetic counseling and early
      screening should be provided to women whose parent had a breast or ovarian cancer
      diagnosis. 

PMID- 24853102
TI  - Requirement for Asn298 on D1 protein for oxygen evolution: analyses by exhaustive
      amino acid substitution in the green alga Chlamydomonas reinhardtii.
AB  - PSII generates strong oxidants used for water oxidation. The secondary electron
      donor, Y(Z), is Tyr161 on PSII reaction center D1 protein and mediates electron
      transfer from the oxygen-evolving Mn(4)CaO(5) cluster to the primary electron
      donor, P680. The latest PSII crystal structure revealed the presence of a
      hydrogen bond network around Y(Z), which is anticipated to play important roles
      in the electron and proton transfer reactions. Y(Z) forms a hydrogen bond with
      His190 which in turn forms a hydrogen bond with Asn298 on D1 protein. Although
      functional roles of Y(Z) and His190 have already been characterized, little is
      known about the functional role of Asn298. Here we have generated 19 mutants from
      a green alga Chlamydomonas reinhardtii, in which the Asn298 has been substituted
      by each of the other 19 amino acid residues. All mutants showed significantly
      impaired or no photosynthetic growth. Seven mutants capable of photosynthetic
      growth showed oxygen-evolving activity although at a significantly reduced rate.
      Interestingly the oxygen-evolving activity of these mutants was markedly
      photosensitive. The 19 mutants accumulated PSII at variable levels and showed a
      light-induced electron transfer reaction from 1,5-diphenylcarbazide (DPC) to 2,6
      dichlorophenolindophenol (DCIP), suggesting that Asn298 is important for the
      function and photoprotection of the Mn(4)CaO(5) cluster.

PMID- 24853103
TI  - Purification and identification of angiotensin I-converting enzyme-inhibitory
      peptides from apalbumin 2 during simulated gastrointestinal digestion.
AB  - BACKGROUND: Bee larvae are considered to be an important reservoir for proteins.
      However, little attention has been paid to the release of potential bioactive
      peptides from bee larva proteins. In this study the major protein in bee larvae
      was hydrolyzed in vitro by gastrointestinal enzymes. The peptide profile of the
      hydrolysis was characterized by gel filtration chromatography and tricine-SDS
      PAGE. Furthermore, the bioactive peptide was isolated and identified by Q-TOF
      MS/MS. RESULTS: The major bee larva protein was identified as apalbumin 2 and was
      more digestible into peptides with molecular weights lower than 3 kDa. The
      hydrolysate obtained after 3 h of digestion exhibited angiotensin I-converting
      enzyme (ACE)-inhibitory activity and was purified sequentially by gel filtration
      and RP-HPLC. The molecular weights of peptide fractions with ACE-inhibitory
      activity were distributed between 0.5 and 1.5 kDa. A novel peptide with highest
      ACE-inhibitory activity (IC50 54.9 umol L(-1) ) was purified by further RP-HPLC.
      The amino acid sequence of this peptide was identified as LLKPY (632.40 Da).
      CONCLUSION: ACE-inhibitory peptides could be formed from bee larvae through
      gastrointestinal digestion. The most active peptide (LLKPY) is potentially useful
      as a therapeutic agent in treating hypertension.

PMID- 24853104
TI  - Comparative study on intestinal metabolism and absorption in vivo of ginsenosides
      in sulphur-fumigated and non-fumigated ginseng by ultra performance liquid
      chromatography quadruple time-of-flight mass spectrometry based chemical
      profiling approach.
AB  - Our previous study indicated that sulphur-fumigation of ginseng in post-harvest
      handling processes could induce chemical transformation of ginsenosides to
      generate multiple ginsenoside sulphur derivatives. In this study, the influence
      of sulphur-fumigation on intestinal metabolism and absorption in vivo of
      ginsenosides in ginseng was sequentially studied. The intestinal metabolic and
      absorbed profiles of ginsenosides in rats after intra-gastric (i.g.)
      administration of sulphur-fumigated ginseng (SFG) and non-fumigated ginseng (NFG)
      were comparatively characterized by a newly established ultra performance liquid
      chromatography quadruple time-of-flight mass spectrometry (UPLC-QTOF-MS/MS) with
      electrospray ionization negative (ESI-) mode. A novel strategy based on the
      characteristic product ions and fragmentation pathways of different types of
      aglycones (saponin skeletons) and glycosyl moieties was proposed and successfully
      applied to rapid structural identification of ginsenoside sulphur derivatives and
      relevant metabolites. In total, 18 ginsenoside sulphur derivatives and 26
      ginsenoside sulphur derivative metabolites in the faeces together with six
      ginsenoside sulphur derivatives in the plasma were identified in the SFG
      administrated group but not in the NFG-administrated group. The results clearly
      demonstrated that the intestinal metabolic and absorbed profiles of ginsenosides
      in sulphur-fumigated and non-fumigated ginseng were quite different, which
      inspired that sulphur-fumigation of ginseng should not be recommended before the
      bioactivity and toxicity of the ginsenoside sulphur derivatives were
      systematically evaluated.

PMID- 24853101
TI  - Mechanisms by which SMARCB1 loss drives rhabdoid tumor growth.
AB  - SMARCB1 (INI1/SNF5/BAF47), a core subunit of the SWI/SNF (BAF) chromatin
      remodeling complex, is inactivated in the large majority of rhabdoid tumors, and
      germline heterozygous SMARCB1 mutations form the basis for rhabdoid
      predisposition syndrome. Mouse models validated Smarcb1 as a bona fide tumor
      suppressor, as Smarcb1 inactivation in mice results in 100% of the animals
      rapidly developing cancer. SMARCB1 was the first subunit of the SWI/SNF complex
      found mutated in cancer. More recently, at least seven other genes encoding
      SWI/SNF subunits have been identified as recurrently mutated in cancer.
      Collectively, 20% of all human cancers contain a SWI/SNF mutation. Consequently,
      investigation of the mechanisms by which SMARCB1 mutation causes cancer has
      relevance not only for rhabdoid tumors, but also potentially for the wide variety
      of SWI/SNF mutant cancers. Here we discuss normal functions of SMARCB1 and the
      SWI/SNF complex as well as mechanistic and potentially therapeutic insights that
      have emerged. 

PMID- 24853105
TI  - Supercritical carbon dioxide extraction of capsaicinoids from malagueta pepper
      (Capsicum frutescens L.) assisted by ultrasound.
AB  - Extracts from malagueta pepper (Capsicum frutescens L.) were obtained using
      supercritical fluid extraction (SFE) assisted by ultrasound, with carbon dioxide
      as solvent at 15MPa and 40 degrees C. The SFE global yield increased up to 77%
      when ultrasound waves were applied, and the best condition of ultrasound-assisted
      extraction was ultrasound power of 360W applied during 60min. Four capsaicinoids
      were identified in the extracts and quantified by high performance liquid
      chromatography. The use of ultrasonic waves did not influence significantly the
      capsaicinoid profiles and the phenolic content of the extracts. However,
      ultrasound has enhanced the SFE rate. A model based on the broken and intact cell
      concept was adequate to represent the extraction kinetics and estimate the mass
      transfer coefficients, which were increased with ultrasound. Images obtained by
      field emission scanning electron microscopy showed that the action of ultrasonic
      waves did not cause cracks on the cell wall surface. On the other hand,
      ultrasound promoted disturbances in the vegetable matrix, leading to the release
      of extractable material on the solid surface. The effects of ultrasound were more
      significant on SFE from larger solid particles. 

PMID- 24853106
TI  - AgI/TiO2 nanocomposites: ultrasound-assisted preparation, visible-light induced
      photocatalytic degradation of methyl orange and antibacterial activity.
AB  - AgI/TiO2 nanocomposites were prepared by an ultrasound-assisted precipitation
      process and subsequent low-temperature (350 degrees C) calcination. The crystal
      phase, morphology and optical properties of the AgI/TiO2 nanocomposites were
      characterized by X-ray diffraction, transmission electron microscopy and UV-vis
      absorption spectroscopy. After calcination, the crystallite size of AgI
      nanoparticles in the AgI/TiO2 nanocomposites decreased, and visible light
      absorption intensity of the AgI/TiO2 nanocomposites was significantly enhanced.
      The AgI/TiO2 nanocomposites after calcination exhibited the superior
      photocatalytic activity for methyl orange degradation and killing of Escherichia
      coli under visible light irradiation. The improvement of photocatalytic activity
      could be attributed to two reasons, namely, reduced crystallite size and enhanced
      visible light absorption of AgI nanoparticles in calcined AgI/TiO2
      nanocomposites. The trapping experiments demonstrated that superoxide radical
      (O2(-)) and holes (h(+)) were the main reactive species for the photodegradation
      of methyl orange under visible light irradiation. The ultrasound-assisted
      preparation approach is efficient and facile, which promotes large-scale
      production and application of AgI/TiO2 nanocomposites in photocatalytic
      degradation of organic pollutants, disinfection and other fields. 

PMID- 24853108
TI  - Ultrasound and modulation assisted synthesis of {[Cu2(BDC-NH2)2(dabco)]DMF.3H2O}
      nanostructures: new precursor to prepare nanorods and nanotubes of copper(II)
      oxide.
AB  - Nanostructures of porous coordination polymer {[Cu2(BDC-NH2)2(dabco)]DMF.3H2O}
      (1) have been synthesized in the presence of acetic acid as a modulator via
      sonochemical method. Different concentrations of metal ions, organic linkers,
      modulator reagent and also different sonication times were held to improve the
      quality and distribution of nanostructures. Ultrasound irradiation helps to
      nucleation step of the oriented attachment of modulation method and nanorods of
      compound 1 has been prepared. Compound 1 was calcinated at 500 degrees C to
      prepare nanorods and nanotubes of copper(II) oxide. Compound 1 and CuO
      nanostructures were characterized by scanning electron microscopy (SEM),
      transmission electron microscopy (TEM) and high resolution transmission electron
      microscopy (HR-TEM), X-ray powder diffraction (XRD) and thermal gravimetric
      analysis (TGA). 

PMID- 24853107
TI  - Ultrasound enhancement of near-neutral photo-Fenton for effective E. coli
      inactivation in wastewater.
AB  - In this study, we attempt for the first time to couple sonication and photo
      Fenton for bacterial inactivation of secondary treated effluent. Synthetic
      wastewater was subjected to sequential high-frequency/low power sonication,
      followed by mild photo-Fenton treatment, under a solar simulator. It was followed
      by the assessment of the contribution of each component of the process (Fenton,
      US, hv) towards the removal rate and the long-term survival; sunlight greatly
      improved the treatment efficiency, with the coupled process being the only one to
      yield total inactivation within the 4-h period of treatment. The short-term
      beneficial disinfecting action of US and its detrimental effect on bacterial
      survival in long term, as well as the impact of light addition were also
      revealed. Finally, an investigation on the operational parameters of the process
      was performed, to investigate possible improvement and/or limitations of the
      coupled treatment; 3 levels of each parameter involved (hydraulic, environmental,
      US and Fenton) were tested. Only H2O2 increased improved the process
      significantly, but the action mode of the joint process indicated potential cost
      effective solutions towards the implementation of this method. 

PMID- 24853109
TI  - Association of maternal education, early infections, and antibiotic use with
      celiac disease: a population-based birth cohort study in northeastern Italy.
AB  - We conducted a population-based birth cohort study of approximately 203,000
      babies born in northeastern Italy (1989-2012) to investigate perinatal variables,
      early infections leading to hospital admission, and antibiotic use in the first
      12 months of life as possible risk factors for celiac disease (CD). Incident CD
      cases were identified from pathology reports, hospital discharge records, and
      exemptions from prescription charges for clinical tests. Multivariate Poisson
      regression models were fitted to estimate incidence rate ratios (IRRs). A total
      of 1,227 children had CD; CD was histopathologically confirmed in 866 (71%).
      Female sex, maternal age, and high maternal educational level were found to be
      significantly associated with CD. Gastrointestinal infections were strongly
      associated with a subsequent diagnosis of CD (IRR = 2.04, 95% confidence interval
      (CI): 1.30, 3.22). Antibiotic use was significantly associated with CD onset (IRR
      = 1.24, 95% CI: 1.07, 1.43), with a dose-response relationship for number of
      courses (P-trend < 0.01). Cephalosporin use strongly increased the risk of CD
      (IRR = 1.42, 95% CI: 1.18, 1.73). Use of antibiotics (supported by the dose
      response relationship) and gastrointestinal infections in the first year of life
      may facilitate the early onset of CD by altering intestinal microflora and the
      gut mucosal barrier. Perinatal factors, including cesarean section, had little
      influence on the risk of childhood CD. 

PMID- 24853111
TI  - Keep an eye on iodine and the thyroid and save the brain.

PMID- 24853110
TI  - Risk for femoral fractures in Parkinson's disease patients with and without
      severe functional impairment.
AB  - BACKGROUND: Impaired balance is a major problem in patients with idiopathic
      Parkinson's disease (PD) resulting in an increased risk of falls and fall-related
      fractures. Most studies which analyzed the risk of femoral fractures in patients
      with idiopathic PD were performed either in specialized centers or excluded very
      frail patients. The current study used a large population-based dataset in order
      to analyze the risk of femoral fractures in patients with idiopathic PD. METHODS:
      Data from more than 880.000 individuals aged 65 years or older and insured
      between 2004 and 2009 at a large German health insurance company were used for
      the analyses. Persons with idiopathic PD were identified by the dispensing of
      Parkinson-specific medication and by hospital diagnoses, if available. People
      without PD served as the reference group. Incident femoral fractures were
      obtained from hospital diagnoses. Analyses were stratified by gender and
      information on severe functional impairment (care need) as provided by
      reimbursement claims. RESULTS: Compared with the reference group, persons with
      idiopathic PD had a more than doubled risk to sustain a femoral fracture. The
      risk was higher in men (HR = 2.61; 95%-CI: 2.28-2.98) than in women (HR = 1.79;
      95%-CI: 1.66-1.94). The increased risk was only observed in people without severe
      functional impairment. The sensitivity analysis using a refined definition of
      idiopathic PD patients yielded similar results. CONCLUSION: The findings confirm
      the increased risk of femoral fractures in patients with idiopathic PD. The
      relative risk is particularly high in male PD patients and in patients without
      severe functional impairment.

PMID- 24853114
TI  - Thermochemical insight into the reduction of CO to CH3OH with [Re(CO)](+) and
      [Mn(CO)](+) complexes.
AB  - To gain insight into thermodynamic barriers for reduction of CO into CH3OH, free
      energies for reduction of [CpRe(PPh3)(NO)(CO)](+) into CpRe(PPh3)(NO)(CH2OH) have
      been determined from experimental measurements. Using model complexes, the free
      energies for the transfer of H(+), H(-), and e(-) have been determined. A pKa of
      10.6 was estimated for [CpRe(PPh3)(NO)(CHOH)](+) by measuring the pKa for the
      analogous [CpRe(PPh3)(NO)(CMeOH)](+). The hydride donor ability (DeltaG degrees
      H(-)) of CpRe(PPh3)(NO)(CH2OH) was estimated to be 58.0 kcal mol(-1), based on
      calorimetry measurements of the hydride-transfer reaction between
      CpRe(PPh3)(NO)(CHO) and [CpRe(PPh3)(NO)(CHOMe)](+) to generate the methylated
      analogue, CpRe(PPh3)(NO)(CH2OMe). Cyclic voltammograms recorded on
      CpRe(PPh3)(NO)(CMeO), CpRe(PPh3)(NO)(CH2OMe), and [CpRe(PPh3)(NO)(CHOMe)](+)
      displayed either a quasireversible oxidation (neutral species) or reduction
      (cationic species). These potentials were used as estimates for the oxidation of
      CpRe(PPh3)(NO)(CHO) or CpRe(PPh3)(NO)(CH2OH) or the reduction of
      [CpRe(PPh3)(NO)(CHOH)](+). Combination of the thermodynamic data permits
      construction of three-dimensional free energy landscapes under varying conditions
      of pH and PH2. The free energy for H2 addition (DeltaG degrees H2) to
      [CpRe(PPh3)(NO)(CO)](+) (+15 kcal mol(-1)) was identified as the most significant
      thermodynamic impediment for the reduction of CO. DFT computations on a series of
      [Cp(X)M(L)(NO)(CO)](+) (M = Re, Mn) complexes indicate that DeltaG degrees H2 can
      be varied by 11 kcal mol(-1) through variation of both the ancillary ligands and
      the metal. 

PMID- 24853112
TI  - Dual RNA-seq of parasite and host reveals gene expression dynamics during
      filarial worm-mosquito interactions.
AB  - BACKGROUND: Parasite biology, by its very nature, cannot be understood without
      integrating it with that of the host, nor can the host response be adequately
      explained without considering the activity of the parasite. However, due to
      experimental limitations, molecular studies of parasite-host systems have been
      predominantly one-sided investigations focusing on either of the partners
      involved. Here, we conducted a dual RNA-seq time course analysis of filarial worm
      parasite and host mosquito to better understand the parasite processes underlying
      development in and interaction with the host tissue, from the establishment of
      infection to the development of infective-stage larva. METHODOLOGY/PRINCIPAL
      FINDINGS: Using the Brugia malayi-Aedes aegypti system, we report parasite gene
      transcription dynamics, which exhibited a highly ordered developmental program
      consisting of a series of cyclical and state-transitioning temporal patterns. In
      addition, we contextualized these parasite data in relation to the concurrent
      dynamics of the host transcriptome. Comparative analyses using uninfected tissues
      and different host strains revealed the influence of parasite development on host
      gene transcription as well as the influence of the host environment on parasite
      gene transcription. We also critically evaluated the life-cycle transcriptome of
      B. malayi by comparing developmental stages in the mosquito relative to those in
      the mammalian host, providing insight into gene expression changes underpinning
      the mosquito-borne parasitic lifestyle of this heteroxenous parasite.
      CONCLUSIONS/SIGNIFICANCE: The data presented herein provide the research
      community with information to design wet lab experiments and select candidates
      for future study to more fully dissect the whole set of molecular interactions of
      both organisms in this mosquito-filarial worm symbiotic relationship.
      Furthermore, characterization of the transcriptional program over the complete
      life cycle of the parasite, including stages within the mosquito, could help
      devise novel targets for control strategies.

PMID- 24853113
TI  - Do women notice the impact of childbirth-related levator trauma on pelvic floor
      and sexual function? Results of an observational ultrasound study.
AB  - INTRODUCTION AND HYPOTHESIS: The levator ani is thought to play an important role
      in sexual function; however, to date little literature has been published on the
      impact of delivery-related levator trauma on female sexual function. We
      hypothesised that delivery-related levator trauma has a negative impact on
      women's reports of pelvic floor and sexual function postpartum. METHODS: In 294
      primigravid women with a singleton pregnancy, four-dimensional (4D) translabial
      ultrasound imaging was used to assess delivery-related levator avulsion and
      levator hiatal over-distension, and postpartum pelvic floor and sexual function
      was assessed by an in-house validated questionnaire. Associations between
      questionnaire responses and levator avulsion and hiatal over-distension were
      investigated using standard linear modelling methods. RESULTS: Levator avulsion
      was diagnosed in 14% of women (42 out of 292; 25 unilateral, 17 bilateral) and
      was found to be significantly associated with lower scores for the pelvic floor
      integrity and function domain of the questionnaire (P < 0.0005). Avulsion was
      associated with lower scores for this domain (no avulsion = 2.78, unilateral
      avulsion = 2.61, bilateral avulsion = 2.29). This association remained
      significant after controlling for potential confounders (p = 0.013). Avulsion was
      not associated with any of the other domains of sexual function and levator
      hiatal over-distension was not associated with scores for any of the
      questionnaire domains. CONCLUSIONS: The effect of levator avulsion on pelvic
      floor and sexual function an average of 5.2 months after childbirth seems to be
      limited to a perception of increased vaginal and pelvic floor muscle laxity, and
      reduced pelvic floor muscle efficiency. The impact of levator hiatal over
      distension on postpartum pelvic floor and sexual function appears to be
      negligible.

PMID- 24853116
TI  - Acarbose monotherapy and weight loss in Eastern and Western populations with
      hyperglycaemia: an ethnicity-specific meta-analysis.
AB  - OBJECTIVE: To demonstrate if weight loss achieved with acarbose in individuals
      with hyperglycaemia differs between Eastern and Western populations. METHODS:
      Databases and reference lists of clinical trials on acarbose were searched.
      Eligible studies were randomised controlled trials of acarbose monotherapy in
      populations with hyperglycaemia of more than 12-week duration that provided data
      on body weight (BW) or body mass index (BMI). RESULTS: A total of 34 trials (6082
      participants) were included. The effect of acarbose on BW was superior to that of
      placebo [weighted mean difference (WMD) = -0.52, 95% confidence interval (CI) 
      0.78 to -0.25], nateglinide (WMD = -1.33, 95% CI -1.51 to -0.75) and metformin
      (WMD = -0.67, 95% CI -1.14 to -0.20). Compared with placebo, there was a
      significantly greater weight loss of 0.92 kg (p < 0.05, I(2)  = 88.8%) with
      acarbose in Eastern populations (WMD = -1.20, 95% CI -1.51 to -0.75) than that in
      Western populations (WMD = -0.28, 95% CI -0.59 to 0.03). Across all studies, the
      acarbose group achieved a significantly larger absolute weight loss of (change
      from baseline) 1.35 kg (p < 0.05, I(2)  = 94.3%) in Eastern populations (WMD = 
      2.26, 95% CI -2.70 to -1.81) than in Western populations (WMD = -0.91, 95% CI 
      1.36 to -0.47). Nevertheless, the possible risk of bias in Eastern studies may
      influence the results. CONCLUSION: The effect of acarbose on weight loss seems to
      be more pronounced in Eastern than in Western populations with hyperglycaemia,
      and is superior to that of placebo, nateglinide and metformin across both
      ethnicities.

PMID- 24853115
TI  - Caries: review of human genetics research.
AB  - The NIH Consensus Development Program released a statement in 2001
      (http://consensus.nih.gov/2001/2001DentalCaries115html.htm) and listed six major
      clinical caries research directions. One of these directions was the need for
      genetic studies to identify genes and genetic markers of diagnostic, prognostic
      and therapeutic value. This last decade has seen a steep increase in studies
      investigating the presence of genetic factors influencing individual
      susceptibility to caries. This review revisits recent caries human genetic
      studies and provides a perspective for future studies in order to fulfil their
      promise of revolutionizing our understanding of and the standard of care for the
      most prevalent bacteria-mediated non-contagious disease in the world.

PMID- 24853117
TI  - A quantum dot-based microRNA nanosensor for point mutation assays.
AB  - We have developed a quantum dot-based microRNA nanosensor for point mutation
      assays using primer generation-mediated rolling circle amplification. The
      proposed method exhibits high sensitivity with a detection limit of as low as
      50.9 aM and a large dynamic range of 7 orders of magnitude from 0.1 fM to 1 nM.
      Importantly, this method can be further applied to analyze the point mutation of
      mir-196a2 in the lung tissues of non small-cell lung cancer patients. 

PMID- 24853118
TI  - Temporal Artery Calciphylaxis Presenting as Temporal Arteritis in a Case of
      Rhinoorbitocerebral Mucormycosis.
AB  - Mucormycosis is a rare often fatal opportunistic fungal infection. It is
      typically described in patients with diabetes in ketoacidotic status and is rare
      in renal transplant recipients. Calciphylaxis is a rare and highly morbid disease
      of vascular calcification affecting patients with end-stage renal disease (ESRD).
      The first case of a renal transplant recipient who was inflicted with both
      rhinoorbitocerebral mucormycosis and calciphylaxis is reported. A 45-year-old man
      presented with 2-day history of left upper blepharoptosis, periorbital pain, left
      sided headache, binocular diplopia, and left V2 numbness. He had undergone renal
      transplant for ESRD 7 months earlier with resultant immunosuppressive therapy.
      MRI and nasal biopsy confirmed rhinoorbitocerebral mucormycosis.
      Immunosuppressive therapy was stopped and antifungal therapy begun. He had
      orbital exenteration for progressive rhinoorbitocerebral mucormycosis. Two months
      later, the patient reported new-onset intermittent bitemporal headache and
      bilateral swollen, tender temporal arteries. Temporal artery biopsy revealed
      features consistent with calciphylaxis. Clinical presentation, treatment course,
      and follow up are discussed. 

PMID- 24853119
TI  - Melkersson-Rosenthal syndrome with isolated unilateral eyelid edema: an
      immunopathologic study.
AB  - Lymphedema is caused by defective drainage of the lymphatic system. In Melkersson
      Rosenthal syndrome, involvement is predominantly of the lumens with blockage of
      lymphatic channels by histiocytic-epithelioid cell clusters accompanied by dermal
      granulomas and lymphocytes. It is a localized, painless, nonitching, and
      nonpitting form of lymphedema. Besides the eyelids, the disease can cause lip
      edema, facial palsy, and/or fissured tongue. It is rare and has received little
      attention in the ophthalmic literature, either in its complete triadic form, or
      more frequently, in its monosymptomatic forms. Pathogenesis is not well
      understood, and there is no effective therapy. The authors describe a case of
      Melkesson-Rosenthal syndrome in a 45-year-old Hispanic man with isolated
      unilateral upper eyelid edema. Histopathological and immunohistochemical
      evaluations of an eyelid biopsy specimen revealed intravascular and extravascular
      clusters of histiocytic-epithelioid cells that were CD68/163-positive. Variable
      numbers of mostly T-lymphocytes were found in the epidermis, dermis, and
      orbicularis muscle and by virtue of the associated granulomas established the
      diagnosis of Melkersson-Rosenthal syndrome. CD4 helper and CD8 suppressor T
      lymphocytes were equally represented. CD20 B-lymphocytes were exceedingly sparse.
      Conspicuous CD1a-positive Langerhans' cells were present in the epidermis,
      sometimes formed subepithelial loose aggregates and were also incorporated in the
      granulomas. The differential diagnosis includes the far more common condition of
      acne rosacea. Management of Melkersson-Rosenthal syndrome, and of angioedema in
      general, is reviewed. 

PMID- 24853120
TI  - Curcuminoid treatment for knee osteoarthritis: a randomized double-blind placebo
      controlled trial.
AB  - Treatment of osteoarthritis (OA) is challenging owing to the inefficacy and long
      term adverse events of currently available medications including non-steroidal
      anti-inflammatory drugs. Curcuminoids are polyphenolic phytochemicals with
      established anti-inflammatory properties and protective effects on chondrocytes.
      The aim of this study is to investigate the clinical efficacy of curcuminoids in
      patients suffering from knee OA. A pilot randomized double-blind placebo-control
      parallel-group clinical trial was conducted among patients with mild-to-moderate
      knee OA. Patients were assigned to curcuminoids (1500 mg/day in 3 divided doses;
      n = 19) or matched placebo (n = 21) for 6 weeks. Efficacy measures were changes
      in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), visual
      analogue scale (VAS) and Lequesne's pain functional index (LPFI) scores during
      the study. There was no significant difference in age, gender, body mass index,
      and VAS, WOMAC and LPFI scores between the study groups at baseline (p > 0.05).
      Treatment with curcuminoids was associated with significantly greater reductions
      in WOMAC (p = 0.001), VAS (p < 0.001) and LPFI (p = 0.013) scores compared with
      placebo. With respect to WOMAC subscales, there were significant improvements in
      the pain and physical function scores (p < 0.001) but not stiffness score (p >
      0.05). There was no considerable adverse effect in both groups. To conclude,
      curcuminoids represent an effective and safe alternative treatment for OA.

PMID- 24853124
TI  - Assembly of BaTiO3 nanocrystals into macroscopic aerogel monoliths with high
      surface area.
AB  - Aerogels with their low density and high surface area are fascinating materials.
      However, their advantageous morphology is still far from being fully exploited
      owing to their limited compositional variety and low crystallinity. Replacing the
      sol-gel process by a particle-based assembly route is a powerful alternative to
      expand the accessible functionalities of aerogels. A strategy is presented for
      the controlled destabilization of concentrated dispersions of BaTiO3
      nanoparticles, resulting in the assembly of the fully crystalline building blocks
      into cylindrically shaped monolithic gels, thereby combining the inherent
      properties of ternary oxides with the highly porous microstructure of aerogels.
      The obtained aerogels showed an unprecedentedly high surface area of over 300
      m(2)  g(-1).

PMID- 24853123
TI  - In silico screening of the key cellular remodeling targets in chronic atrial
      fibrillation.
AB  - Chronic atrial fibrillation (AF) is a complex disease with underlying changes in
      electrophysiology, calcium signaling and the structure of atrial myocytes. How
      these individual remodeling targets and their emergent interactions contribute to
      cell physiology in chronic AF is not well understood. To approach this problem,
      we performed in silico experiments in a computational model of the human atrial
      myocyte. The remodeled function of cellular components was based on a broad
      literature review of in vitro findings in chronic AF, and these were integrated
      into the model to define a cohort of virtual cells. Simulation results indicate
      that while the altered function of calcium and potassium ion channels alone
      causes a pronounced decrease in action potential duration, remodeling of
      intracellular calcium handling also has a substantial impact on the chronic AF
      phenotype. We additionally found that the reduction in amplitude of the calcium
      transient in chronic AF as compared to normal sinus rhythm is primarily due to
      the remodeling of calcium channel function, calcium handling and cellular
      geometry. Finally, we found that decreased electrical resistance of the membrane
      together with remodeled calcium handling synergistically decreased cellular
      excitability and the subsequent inducibility of repolarization abnormalities in
      the human atrial myocyte in chronic AF. We conclude that the presented results
      highlight the complexity of both intrinsic cellular interactions and emergent
      properties of human atrial myocytes in chronic AF. Therefore, reversing
      remodeling for a single remodeled component does little to restore the normal
      sinus rhythm phenotype. These findings may have important implications for
      developing novel therapeutic approaches for chronic AF. 

PMID- 24853122
TI  - Impact of ASHA training on active case detection of visceral leishmaniasis in
      Bihar, India.
AB  - BACKGROUND: One of the major challenges for management of visceral leishmaniasis
      (VL) is early diagnosis of cases to improve treatment outcome and reduce
      transmission. We have therefore investigated active case detection of VL with the
      help of accredited social health activists (ASHA). ASHAs are women who live in
      the community and receive performance-based incentives for overseeing maternal
      and other health-related issues in their village. METHODS AND PRINCIPAL FINDING:
      Through conducting interviews with 400 randomly selected ASHAs from four primary
      health care centers (PHCs), it was observed that their level of knowledge about
      visceral leishmaniasis (VL) regarding transmission, diagnosis, and treatment was
      limited. The baseline data indicated that less than 10% of VL cases seeking
      treatment at the PHCs were referred by ASHAs. To increase the knowledge and the
      referral rate of VL cases by ASHAs, training sessions were carried out during the
      monthly ASHA meetings at their respective PHCs. Following a single training
      session, the referral rate increased from less than 10% to over 27% and the
      overall knowledge about VL substantially improved. It was not possible, however,
      to demonstrate that ASHA training reduced the time that individuals had fever
      before treatment at the PHC. CONCLUSIONS: Training ASHAs to identify VL cases in
      villages for early diagnosis and treatment at the local PHC is feasible and
      should be undertaken routinely to improve knowledge about VL.

PMID- 24853121
TI  - Pre-clinical characterization of Dacomitinib (PF-00299804), an irreversible pan
      ErbB inhibitor, combined with ionizing radiation for head and neck squamous cell
      carcinoma.
AB  - Epidermal growth factor receptor (EGFR) is over-expressed in nearly all cases of
      squamous cell carcinoma of the head and neck (SCCHN), and is an important driver
      of disease progression. EGFR targeted therapies have demonstrated clinical
      benefit for SCCHN treatment. In this report, we investigated the pre-clinical
      efficacy of Dacomitinib (PF-00299804), an irreversible pan-ErbB inhibitor, both
      alone and in combination with ionizing radiation (IR), a primary curative
      modality for SCCHN. One normal oral epithelial (NOE) and three SCCHN (FaDu, UT
      SCC-8, UT-SCC-42a) cell lines were used to conduct cell viability, clonogenic
      survival, cell cycle, and immunoblotting assays in vitro, using increasing doses
      of Dacomitinib (10-500 nM), both with and without IR (2-4 Gy). The FaDu xenograft
      model was utilized for tumor growth delay assays in vivo, and immunohistochemical
      analyses were conducted on extracted tumors. A dose-dependent reduction in cell
      viability and clonogenic survival after Dacomitinib treatment was observed in all
      three SCCHN models. Treatment led to a significant reduction in EGFR signalling,
      with a subsequent decrease in phosphorylation of downstream targets such as ERK,
      AKT, and mTOR. In vivo, Dacomitinib treatment delayed tumor growth, while
      decreasing phospho-EGFR and Ki-67 immunoexpression. These effects were further
      enhanced when combined with IR, both in vitro and in vivo. The preclinical data
      support the further evaluations of Dacomitinib combined with IR for the future
      management of patients with SCCHN. 

PMID- 24853126
TI  - Influence of Belousov-Zhabotinsky substrate concentrations on autonomous
      oscillation of polymer chains with Fe(bpy)3 catalyst.
AB  - We studied the effect of initial substrate concentrations in the Belousov
      Zhabotinsky (BZ) reaction on the optical transmittance self-oscillation behavior
      of a polymer chain consisting of N-isopropylacrylamide (NIPAAm) and a Fe catalyst
      ([Fe(bpy)3]). The driving force of this transmittance self-oscillation was the
      solubility difference between the reduced and oxidized states of the [Fe(bpy)3]
      moiety in the polymer chain. The amplitude of the soluble-insoluble self
      oscillation of poly(NIPAAm-co-[Fe(bpy)3]) was significantly smaller than that of
      poly(NIPAAm-co-[Ru(bpy)3]). Theoretical simulation results attributed this
      behavior to the small difference in the solvent qualities, C*, of the reduced and
      oxidized states. Furthermore, we clarified that poly(NIPAAm-co-[Fe(bpy)3])
      required a narrower concentration range of HNO3 to exhibit self-oscillation than
      poly(NIPAAm-co-[Ru(bpy)3]), since transmittance self-oscillation occurred only
      for [HNO3] = 0.3 M. The period of self-oscillation of poly(NIPAAm-co-[Fe(bpy)3])
      in solution was controlled mainly by NaBrO3 concentration and was hardly
      influenced by the initial concentration of malonic acid. 

PMID- 24853125
TI  - Transient myeloproliferative disorder in neonates without Down syndrome: case
      report and review.
AB  - Transient myeloproliferative disorder (TMD) is a clonal proliferation of
      megakaryoblasts, typically occurring in newborns with Down syndrome. It is
      believed that TMD occurs in the presence of GATA1 mutation together with trisomy
      21. However, a limited number of patients with TMD but without Down syndrome have
      been reported, all with a blast population with numeric or rarely structural
      chromosome 21 abnormalities. We present the first case of a newborn boy with a
      TMD without trisomy 21 and without any of the mentioned molecular or cytogenetic
      abnormalities. This case report suggests that unknown disease mechanisms may
      provoke or mimic TMD. This case report is followed by a concise review of the
      literature discussing the different entities and pathomechanisms of TMD and acute
      megakaryocytic leukaemia in patients with or without Down syndrome. 

PMID- 24853127
TI  - Tagging SNPs in the MTHFR gene and risk of ischemic stroke in a Chinese
      population.
AB  - Stroke is currently the leading cause of functional impairments worldwide. Folate
      supplementation is inversely associated with risk of ischemic stroke.
      Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme involved in
      folate metabolism. The aim of this study is to examine whether genetic variants
      in MTHFR gene are associated with the risk of ischemic stroke and fasting total
      serum homocysteine (tHcy) level. We genotyped nine tag SNPs in the MTHFR gene in
      a case-control study, including 543 ischemic stroke cases and 655 healthy
      controls in China. We found that subjects with the rs1801133 TT genotype and
      rs1801131 CC genotype had significant increased risks of ischemic stroke
      (adjusted odds ratio (OR)=1.82, 95% confidence interval (CI): 1.27-2.61, p=0.004;
      adjusted OR=1.99, 95% CI: 1.12-3.56, p=0.01) compared with subjects with the
      major alleles. Haplotype analysis also found that carriers of the MTHFR CTTCGA
      haplotype (rs12121543-rs13306553-rs9651118-rs1801133-rs2274976-rs1801131) had a
      significant reduced risk of ischemic stroke (adjusted OR=0.53, 95% CI: 0.35-0.82)
      compared with those with the CTTTGA haplotype. Besides, the MTHFR rs1801133 and
      rs9651118 were significantly associated with serum levels of tHcy in healthy
      controls (p<0.0001 and p=0.02). These findings suggest that variants in the MTHFR
      gene may influence the risk of ischemic stroke and serum tHcy.

PMID- 24853128
TI  - Synthesis and bioactivity of 5-substituted-2-furoyl diacylhydazide derivatives
      with aliphatic chain.
AB  - A series of 5-substituted-2-furoyl diacylhydazide derivatives with aliphatic
      chain were designed and synthesized. Their structures were characterized by IR,
      1H NMR, elemental analysis, and X-ray single crystal diffraction. The anti-tumor
      bioassay revealed that some title compounds exhibited promising activity against
      the selected cancer cell lines, especially against the human promyelocytic
      leukemic cells (HL-60). Their fungicidal tests indicated that most of the title
      compounds showed significant anti-fungal activity. The preliminary structure
      activity relationship showed that the aliphatic chain length and differences in
      the R2 group had obvious effects on the anti-tumor and anti-fungal activities.
      The bioassay results demonstrated that the title compounds hold great promise as
      novel lead compounds for further drug discovery. 

PMID- 24853129
TI  - Genes and gene networks involved in sodium fluoride-elicited cell death
      accompanying endoplasmic reticulum stress in oral epithelial cells.
AB  - Here, to understand the molecular mechanisms underlying cell death induced by
      sodium fluoride (NaF), we analyzed gene expression patterns in rat oral
      epithelial ROE2 cells exposed to NaF using global-scale microarrays and
      bioinformatics tools. A relatively high concentration of NaF (2 mM) induced cell
      death concomitant with decreases in mitochondrial membrane potential, chromatin
      condensation and caspase-3 activation. Using 980 probe sets, we identified 432 up
      regulated and 548 down-regulated genes, that were differentially expressed by
      >2.5-fold in the cells treated with 2 mM of NaF and categorized them into 4
      groups by K-means clustering. Ingenuity(r) pathway analysis revealed several gene
      networks from gene clusters. The gene networks Up-I and Up-II included many up
      regulated genes that were mainly associated with the biological function of
      induction or prevention of cell death, respectively, such as Atf3, Ddit3 and Fos
      (for Up-I) and Atf4 and Hspa5 (for Up-II). Interestingly, knockdown of Ddit3 and
      Hspa5 significantly increased and decreased the number of viable cells,
      respectively. Moreover, several endoplasmic reticulum (ER) stress-related genes
      including, Ddit3, Atf4 and Hapa5, were observed in these gene networks. These
      findings will provide further insight into the molecular mechanisms of NaF
      induced cell death accompanying ER stress in oral epithelial cells. 

PMID- 24853130
TI  - Transition from cyclosporine-induced renal dysfunction to nephrotoxicity in an in
      vivo rat model.
AB  - Cyclosporin A (CsA), a calcineurin inhibitor, remain the cornerstone of
      immunosuppressive regimens, regardless of nephrotoxicity, which depends on the
      duration of drug exposure. The mechanisms and biomarkers underlying the
      transition from CsA-induced renal dysfunction to nephrotoxicity deserve better
      elucidation, and would help clinical decisions. This study aimed to clarify these
      issues, using a rat model of short- and long-term CsA (5 mg/kg bw/day) treatments
      (3 and 9 weeks, respectively). Renal function was assessed on serum and urine;
      kidney tissue was used for histopathological characterization and gene and/or
      protein expression of markers of proliferation, fibrosis and inflammation. In the
      short-term, creatinine and blood urea nitrogen (BUN) levels increased and
      clearances decreased, accompanied by glomerular filtration rate (GFR) reduction,
      but without kidney lesions; at that stage, CsA exposure induced proliferating
      cell nuclear antigen (PCNA), transforming growth factor beta 1 (TGF-beta1),
      factor nuclear kappa B (NF-kappabeta) and Tumor Protein P53 (TP53) kidney mRNA up
      regulation. In the long-term treatment, renal dysfunction data was accompanied by
      glomerular and tubulointerstitial lesions, with remarkable kidney mRNA up
      regulation of the mammalian target of rapamycin (mTOR) and the antigen identified
      by monoclonal antibody Ki-67 (Mki67), accompanied by mTOR protein overexpression.
      Transition from CsA-induced renal dysfunction to nephrotoxicity is accompanied by
      modification of molecular mechanisms and biomarkers, being mTOR one of the key
      players for kidney lesion evolution, thus suggesting, by mean of molecular
      evidences, that early CsA replacement by mTOR inhibitors is indeed the better
      therapeutic choice to prevent chronic allograft nephropathy. 

PMID- 24853131
TI  - Effect of a novel quaternary ammonium methacrylate polymer (QAMP) on adhesion and
      antibacterial properties of dental adhesives.
AB  - This study investigated the resin-dentin bond strength (MUTBS), degree of
      conversion (DC), and antibacterial potential of an innovative adhesive system
      containing a quaternary ammonium methacrylate polymer (QAMP) using in situ and in
      vitro assays. Forty-two human third molars were flattened until the dentin was
      exposed and were randomly distributed into three groups of self-etching adhesive
      systems: ClearfilTM SE Bond containing 5% QAMP (experimental group), ClearfilTM
      Protect Bond (positive control) and ClearfilTM SE Bond (negative control). After
      light curing, three 1 mm-increments of composite resin were bonded to each dentin
      surface. A total of thirty of these bonded teeth (10 teeth per group) was
      sectioned to obtain stick-shaped specimens and tested under tensile stress
      immediately, and after 6 and 12 months of storage in distilled water. Twelve
      bonded teeth (4 teeth per group) were longitudinally sectioned in a mesio-to
      distal direction to obtain resin-bonded dentin slabs. In situ DC was evaluated by
      micro-Raman spectroscopy. In vitro DC of thin films of each adhesive system was
      measured using Fourier transform infrared spectroscopy. In vitro susceptibility
      tests of these three adhesive systems were performed by the minimum
      inhibitory/minimum bactericidal concentration (MIC/MBC) assays against
      Streptococcus mutans, Lactobacillus casei, and Actinomyces naeslundii. No
      statistically significant difference in MUTBS was observed between ClearfilTM SE
      Bond containing 5% QAMP and ClearfilTM SE Bond (p>0.05) immediately, and after 6
      and 12 months of water storage. However ClearfilTM Protect Bond showed a
      significant reduction of MUTBS after 12 months of storage (p=0.039). In addition,
      QAMP provided no significant change in DC after incorporating into ClearfilTM SE
      Bond (p>0.05). ClearfilTM SE Bond containing 5% QAMP demonstrated MIC/MBC values
      similar to the positive control against L. casei and A. naeslundii and higher
      than the negative control for all evaluated bacterial strains. The use of QAMP in
      an adhesive system demonstrated effective bond strength, a suitable degree of
      conversion, and adequate antibacterial effects against oral bacteria, and may be
      useful as a new approach to provide long-lasting results for dental adhesives.

PMID- 24853133
TI  - Integrated assessment of metal contamination in sediments from two tropical
      estuaries.
AB  - In order to evaluate if sediment metal contamination is responsible for benthic
      degradation and identify possible reference sites in Todos os Santos Bay (TSB),
      comparisons between a highly impacted (Subae) and less impacted (Jaguaripe)
      estuarine systems were made based on (i) field assessment of macrobenthic
      assemblage, (ii) sediment metal concentrations and (iii) chronic toxicity test
      with the tropical copepod Nitokra sp. Data were integrated by multivariate
      analysis (BIOENV and PCA) and the ratio-to-mean (RTMe) approach. Estuaries were
      divided into four different salinity zones to avoid misclassification of benthic
      conditions. Salinity was the main variable correlated to the benthic distribution
      in both estuaries, indicating that categories based on salinity features seem to
      be suitable in TSB. Correspondence among lines of evidence differed in low and
      high metal contaminated systems. Chronic toxicity was found along both the entire
      systems, being considerably higher in Jaguaripe. However, there was no clear
      evidence of metal contamination and benthic alteration in most stations of
      Jaguaripe. Although the concentrations of Sr and Cu were correlated to the
      benthic assemblage in Jaguaripe, it is unlikely that toxicity has been caused by
      these elements. The benthic assemblage distribution of Jaguaripe seems to be
      rather related to natural stressful conditions of transitional waters. Even
      though the Jaguaripe estuary might not be pristine, it can be used as a reference
      estuary for benthic assessment in TSB. Regarding the Subae estuary, toxicity and
      Zn were also correlated to the benthic assemblage and most stations showed signs
      of benthic alteration and metal contamination. All lines of evidence were in
      agreement providing evidences that metal contamination might be responsible for
      benthic degradation in Subae. 

PMID- 24853132
TI  - Mangiferin facilitates islet regeneration and beta-cell proliferation through
      upregulation of cell cycle and beta-cell regeneration regulators.
AB  - Mangiferin, a xanthonoid found in plants including mangoes and iris unguicularis,
      was suggested in previous studies to have anti-hyperglycemic function, though the
      underlying mechanisms are largely unknown. This study was designed to determine
      the therapeutic effect of mangiferin by the regeneration of beta-cells in mice
      following 70% partial pancreatectomy (PPx), and to explore the mechanisms of
      mangiferin-induced beta-cell proliferation. For this purpose, adult C57BL/6J mice
      after 7-14 days post-PPx, or a sham operation were subjected to mangiferin (30
      and 90 mg/kg body weight) or control solvent injection. Mangiferin-treated mice
      exhibited an improved glycemia and glucose tolerance, increased serum insulin
      levels, enhanced beta-cell hyperplasia, elevated beta-cell proliferation and
      reduced beta-cell apoptosis. Further dissection at the molecular level showed
      several key regulators of cell cycle, such as cyclin D1, D2 and cyclin-dependent
      kinase 4 (Cdk4) were significantly up-regulated in mangiferin-treated mice. In
      addition, critical genes related to beta-cell regeneration, such as pancreatic
      and duodenal homeobox 1 (PDX-1), neurogenin 3 (Ngn3), glucose transporter 2 (GLUT
      2), Forkhead box protein O1 (Foxo-1), and glucokinase (GCK), were found to be
      promoted by mangiferin at both the mRNA and protein expression level. Thus,
      mangiferin administration markedly facilitates beta-cell proliferation and islet
      regeneration, likely by regulating essential genes in the cell cycle and the
      process of islet regeneration. These effects therefore suggest that mangiferin
      bears a therapeutic potential in preventing and/or treating the diabetes. 

PMID- 24853134
TI  - Effects of chemical and thermal stress on acetylcholinesterase activity in the
      brain of the bank vole, Myodes glareolus.
AB  - One of the most important issues in ecotoxicology is better understanding the
      effects of interactions between chemical pollutants and physical environmental
      factors on animals. To fill this knowledge gap, changes in the activity of
      acetylcholinesterase (AChE) in the brain samples of bank voles Myodes
      (Clethrionomys) glareolus due to temperature effects, and two chemical stressors
      were studied in a full factorial laboratory experiment (27 treatments). The
      experiment was divided into three phases: acclimatisation (3 days), intoxication
      (42 days) and elimination (21 days). During the intoxication phase, animals were
      orally exposed to different concentrations of either nickel (0, 300 or 800 mg
      Ni/kg food), chlorpyrifos (CPF) (0, 50 or 350 mg CPF/kg food) or a mixture of
      both chemicals. During the acclimatisation and elimination phases, the bank voles
      were given uncontaminated food. The experiment was conducted at three different
      temperatures (10, 20 or 30  degrees C), and a 12 h:12 h light:dark regime. The
      animals were sacrificed at 0, 5, 10, 20, 42, 49 and 63 days after the beginning
      of the intoxication, and brain samples were obtained for chemical analysis. The
      nickel accumulation in the brain depended on the level of nickel exposure and on
      interactions between the temperature and other factors. Nickel exhibited no
      effect on AChE activity. In contrast, AChE was drastically inhibited by
      chlorpyrifos and low temperature, but interactions between all factors
      significantly influenced the enzyme activity during the elimination phase of the
      experiment. High mortality was observed in the groups exposed to high
      concentrations of nickel and chlorpyrifos.

PMID- 24853136
TI  - Physical, chemical, and biological characteristics of compounds used in hydraulic
      fracturing.
AB  - Hydraulic fracturing (HF), a method to enhance oil and gas production, has become
      increasingly common throughout the U.S. As such, it is important to characterize
      the chemicals found in HF fluids to evaluate potential environmental fate,
      including fate in treatment systems, and human health impacts. Eighty-one common
      HF chemical additives were identified and categorized according to their
      functions. Physical and chemical characteristics of these additives were
      determined using publicly available chemical information databases. Fifty-five of
      the compounds are organic and twenty-seven of these are considered readily or
      inherently biodegradable. Seventeen chemicals have high theoretical chemical
      oxygen demand and are used in concentrations that present potential treatment
      challenges. Most of the HF chemicals evaluated are non-toxic or of low toxicity
      and only three are classified as Category 2 oral toxins according to standards in
      the Globally Harmonized System of Classification and Labeling of Chemicals;
      however, toxicity information was not located for thirty of the HF chemicals
      evaluated. Volatilization is not expected to be a significant exposure pathway
      for most HF chemicals. Gaps in toxicity and other chemical properties suggest
      deficiencies in the current state of knowledge, highlighting the need for further
      assessment to understand potential issues associated with HF chemicals in the
      environment. 

PMID- 24853137
TI  - Application of cetyltrimethylammonium bromide bentonite-titanium dioxide
      photocatalysis technology for pretreatment of aging leachate.
AB  - Organobentonite-photocatalysis technology was applied to pretreat aging leachate
      containing refractory pollutants. The organobentonite was synthesized by organic
      modifier cetyltrimethylammonium bromide (CTMAB) and natural bentonite. In
      characterization experiments, we could confirm that organic functional groups of
      cetyltrimethylammonium (CTMA(+)) cations were successfully loaded on the surface
      of bentonite. The combination of CTMAB2.5 adsorption and TiO2 photocatalysis was
      superior to either running separately. Furthermore, removal efficiency of
      simultaneously utilizing CTMAB2.5 and TiO2 was better than them in succession.
      The combination technology was feasible and was optimized by response surface
      methodology (RSM) with COD and NH3-N removal rate as the target responses. The
      optimal operation conditions calculated from the regression equations were
      CTMAB2.5 dosage of 7.5 g/L, pH at 3.5, TiO2 dosage of 1.63 g/L, and reaction time
      for 60.02 min, which maintained the removal of COD and NH3-N at 82% and 37%,
      respectively.

PMID- 24853135
TI  - The role of the anterior insula in adolescent decision making.
AB  - Much recent research on adolescent decision making has sought to characterize the
      neurobiological mechanisms that underlie the proclivity of adolescents to engage
      in risky behavior. One class of influential neurodevelopmental models focuses on
      the asynchronous development of neural systems, particularly those responsible
      for self-regulation and reward seeking. While this work has largely focused on
      the development of prefrontal (self-regulation) and striatal (reward processing)
      circuitry, the present article explores the significance of a different region,
      the anterior insular cortex (AIC), in adolescent decision making. Although the
      AIC is known for its role as a cognitive-emotional hub, and is included in some
      models of adult self-regulation and reward seeking, the importance of the AIC and
      its maturation in adolescent risk taking has not been extensively explored. In
      this article we discuss evidence on AIC development, and consider how age-related
      differences in AIC engagement may contribute to heightened risk taking during
      adolescence. Based on this review, we propose a model in which the engagement of
      adolescents in risk taking may be linked in part to the maturation of the AIC and
      its connectivity to the broader brain networks in which it participates.

PMID- 24853138
TI  - Use of a moss biomonitoring method to compile emission inventories for small
      scale industries.
AB  - We used a method of detecting small-scale pollution sources (DSSP) that involves
      measurement of the concentrations of elements in moss tissues, with the following
      aims: (i) to determine any common qualitative patterns of contaminant emissions
      for individual industrial sectors, (ii) to compare any such patterns with
      previously described patterns, and (iii) to compile an inventory of the metals
      and metalloids emitted by the industries considered. Cluster analysis revealed
      that there were no common patterns of emission associated with the industrial
      sectors, probably because of differences in production processes and in the types
      of fuel and raw materials. However, when these variables were shared by different
      factories, the concentrations of the elements in moss tissues enabled the
      factories to be grouped according to their emissions. We compiled a list of the
      metals and metalloids emitted by the factories under study and found that the
      DSSP method was satisfactory for this purpose in most cases (53 of 56). The
      method appears to be a useful tool for compiling contaminant inventories; it may
      also be useful for determining the efficacy of technical improvements aimed at
      reducing the industrial emission of contaminants and could be incorporated in
      environmental monitoring and control programmes. 

PMID- 24853139
TI  - Transport and retention of zinc oxide nanoparticles in porous media: effects of
      natural organic matter versus natural organic ligands at circumneutral pH.
AB  - The potential toxicity of nanoparticles (NPs) has received considerable
      attention, but there is little knowledge relating to the fate and transport of
      engineered ZnO NPs in the environment. Column experiments were performed at pH
      7.3-7.6 to generate effluent concentrations and retention profiles for assessing
      the fate and transport of ZnO NPs (PZC=9.3, nominal size 20 nm) in saturated
      quartz sands (256 MUm) in the presence of low natural organic matter (NOM)
      concentrations (1 mg/L humic and fulvic acids) and millimolar natural organic
      ligands (NOL) levels (formic, oxalic, and citric acids). At circumneutral pHs,
      ZnO NPs were positively charged and immobile in sand. The presence of NOM
      decreased the attachment efficiency facilitating ZnO transport through sand
      columns. Conversely, ZnO transport in the presence of formic and oxalic acids was
      only slightly improved when compared to ZnO in DI water; whereas, citric acid
      showed no improvement. The distinct difference between NOM and NOL may have
      important implications with regard to ZnO transport in the subsurface
      environment. Experimental results suggested the presence of both favorable and
      unfavorable nanoparticle interactions causes significant deviations from
      classical colloid filtration theory (CFT).

PMID- 24853140
TI  - Effects of the interaction of single-walled carbon nanotubes with 4-nonylphenol
      on their in vitro toxicity.
AB  - The aim of this study was to assess the toxicological risks arising from the
      coexistence of polyethylene glycol coated single-walled carbon nanotubes (SWCNTs
      PEG) and a known environmental contaminant: 4-nonylphenol (NP). To this end, in
      vitro toxicity assays involving the exposure of 3T3-L1 cells (mouse embryonic
      fibroblasts) to SWCNTs-PEG alone or in combination with NP for 24 or 48 h were
      performed. Experimental treatments were conducted in both presence (10%) and
      absence of serum in order to evaluate its influence on the toxicity of SWCNTs
      PEG. Although the results provided no unambiguous evidences of synergistic
      toxicity between SWCNTs-PEG and NP, some specific treatments with mixtures
      (SWCNTs-PEG+NP) resulted in an unexpected combined toxicity in relation to the
      individual treatments. Only in those cases the interaction between SWCNTs-PEG and
      NP could have a synergistic effect on the resulting toxicity. The addition of 10%
      serum increased the stability of SWCNTs-PEG in the culture medium-possibly by
      steric repulsions-and reduced the toxicity of nanoparticles as a result. Overall,
      the serum had a "protective effect" on cells against all treatments: SWCNTs-PEG,
      NP or their mixtures (SWCNTs-PEG+NP). Raman spectroscopy allowed the
      intracellular distribution of SWCNTs-PEG to be elucidated.

PMID- 24853142
TI  - Cardiotoxicity evaluation of anthracyclines in zebrafish (Danio rerio).
AB  - Drug-induced cardiotoxicity is a leading factor for drug withdrawals, and limits
      drug efficacy and clinical use. Therefore, new alternative animal models and
      methods for drug safety evaluation have been given great attention.
      Anthracyclines (ANTs) are widely prescribed anticancer agents that have a
      cumulative dose relationship with cardiotoxicity. We performed experiments to
      study the toxicity of ANTs in early developing zebrafish embryos, especially
      their effects on the heart. LC50 values for daunorubicin, pirarubicin,
      doxorubicin (DOX), epirubicin and DOX-liposome at 72 h post-fertilization were
      122.7 MUM, 111.9 MUM, 31.2 MUM, 108.3 MUM and 55.8 MUM, respectively. At the same
      time, zebrafish embryos were exposed to ANTs in three exposure stages and induced
      incomplete looping of the heart tube, pericardia edema and bradycardia in a dose
      dependent manner, eventually leading to death. DOX caused the greatest heart
      defects in the treatment stages and its liposome reduced the effects on the
      heart, while daunorubicin produced the least toxicity. Genes and proteins related
      to heart development were also identified to be sensitive to ANT exposure and
      downregulated by ANTs. It revealed ANTs could disturb the heart formation and
      development. ANTs induced cardiotoxicity in zebrafish has similar effects in
      mammalian models, indicating that zebrafish may have a potential value for
      assessment of drug-induced developmental cardiotoxicity.

PMID- 24853143
TI  - Source of prescription drugs used nonmedically in rural and urban populations.
AB  - BACKGROUND: Unintentional overdose deaths due to nonmedical use of prescription
      drugs disproportionately impact rural over urban settings in the United States.
      Sources of these prescriptions may play a factor. OBJECTIVE: This study examines
      the relationships between rurality and source of prescription drugs used
      nonmedically. METHODS: Using data from the National Survey on Drug Use and Health
      2008-2010 (n = 10 693), we examined bivariate and multivariate associations of
      socio-demographic and clinical correlates and source (physician or non-physician)
      of prescription drugs (opioid, sedative, tranquilizer, or stimulant) used
      nonmedically among urban and rural residents. We also examined the type of
      prescription drugs used nonmedically among urban and rural residents by source.
      RESULTS: Among respondents reporting past year nonmedical use of prescription
      medications, 18.9% of urban residents and 17.5% of rural residents had a
      physician source for drugs used nonmedically. Likelihood of physician source for
      urban and rural residents was increased in Hispanic, insured individuals and
      those with any prescription drug dependence. Rural residents who had a non
      physician source were more likely than urban residents with a non-physician
      source to use hydrocodone (49% vs. 43.3%, p = 0.05), morphine (17.7% vs. 14.0%, p
      = 0.04), tramadol products (18.1% vs. 11.2%, p = 0.003), and methadone (17.2% vs.
      10.9%, p = 0.001). CONCLUSION: Urban and rural individuals with nonmedical use of
      prescription drugs are equally likely to obtain these prescriptions from a
      physician source. Some factors associated with obtaining prescription drugs from
      a physician source differed between these populations, which may have
      implications for public health approaches to addressing problems such as
      overdose.

PMID- 24853141
TI  - HCC development is associated to peripheral insulin resistance in a mouse model
      of NASH.
AB  - NAFLD is the most common liver disease worldwide but it is the potential
      evolution to NASH and eventually to hepatocellular carcinoma (HCC), even in the
      absence of cirrhosis, that makes NAFLD of such clinical importance. AIM: we aimed
      to create a mouse model reproducing the pathological spectrum of NAFLD and to
      investigate the role of possible co-factors in promoting HCC. METHODS: mice were
      treated with a choline-deficient L-amino-acid-defined-diet (CDAA) or its control
      (CSAA diet) and subjected to a low-dose i.p. injection of CCl4 or vehicle.
      Insulin resistance was measured by the euglycemic-hyperinsulinemic clamp method.
      Steatosis, fibrosis and HCC were evaluated by histological and molecular
      analysis. RESULTS: CDAA-treated mice showed peripheral insulin resistance at 1
      month. At 1-3 months, extensive steatosis and fibrosis were observed in CDAA and
      CDAA+CCl4 groups. At 6 months, equal increase in steatosis and fibrosis was
      observed between the two groups, together with the appearance of tumor. At 9
      months of treatment, the 100% of CDAA+CCl4 treated mice revealed tumor versus 40%
      of CDAA mice. Insulin-like Growth Factor-2 (IGF-2) and Osteopontin (SPP-1) were
      increased in CDAA mice versus CSAA. Furthermore, Immunostaining for p-AKT, p-c
      Myc and Glypican-3 revealed increased positivity in the tumors. CONCLUSIONS: the
      CDAA model promotes the development of HCC from NAFLD-NASH in the presence of
      insulin resistance but in the absence of cirrhosis. Since this condition is
      increasingly recognized in humans, our study provides a model that may help
      understanding mechanisms of carcinogenesis in NAFLD.

PMID- 24853145
TI  - Automated cardiac sarcomere analysis from second harmonic generation images.
AB  - Automatic quantification of cardiac muscle properties in tissue sections might
      provide important information related to different types of diseases. Second
      harmonic generation (SHG) imaging provides a stain-free microscopy approach to
      image cardiac fibers that, combined with our methodology of the automated
      measurement of the ultrastructure of muscle fibers, computes a reliable set of
      quantitative image features (sarcomere length, A-band length, thick-thin
      interaction length, and fiber orientation). We evaluated the performance of our
      methodology in computer-generated muscle fibers modeling some artifacts that are
      present during the image acquisition. Then, we also evaluated it by comparing it
      to manual measurements in SHG images from cardiac tissue of fetal and adult
      rabbits. The results showed a good performance of our methodology at high signal
      to-noise ratio of 20 dB. We conclude that our automated measurements enable
      reliable characterization of cardiac fiber tissues to systematically study
      cardiac tissue in a wide range of conditions.

PMID- 24853144
TI  - Improving intra-fractional target position accuracy using a 3D surface surrogate
      for left breast irradiation using the respiratory-gated deep-inspiration breath
      hold technique.
AB  - PURPOSE: To evaluate the use of 3D optical surface imaging as a surrogate for
      respiratory gated deep-inspiration breath-hold (DIBH) for left breast
      irradiation. MATERIAL AND METHODS: Patients with left-sided breast cancer treated
      with lumpectomy or mastectomy were selected as candidates for DIBH treatment for
      their external beam radiation therapy. Treatment plans were created on both free
      breathing (FB) and DIBH computed tomography (CT) simulation scans to determine
      dosimetric benefits from DIBH. The Real-time Position Management (RPM) system was
      used to acquire patient's breathing trace during DIBH CT acquisition and
      treatment delivery. The reference 3D surface models from FB and DIBH CT scans
      were generated and transferred to the "AlignRT" system for patient positioning
      and real-time treatment monitoring. MV Cine images were acquired during treatment
      for each beam as quality assurance for intra-fractional position verification.
      The chest wall excursions measured on these images were used to define the actual
      target position during treatment, and to investigate the accuracy and
      reproducibility of RPM and AlignRT. RESULTS: Reduction in heart dose can be
      achieved using DIBH for left breast/chest wall radiation. RPM was shown to have
      inferior correlation with the actual target position, as determined by the MV
      Cine imaging. Therefore, RPM alone may not be an adequate surrogate in defining
      the breath-hold level. Alternatively, the AlignRT surface imaging demonstrated a
      superior correlation with the actual target positioning during DIBH. Both the
      vertical and magnitude real-time deltas (RTDs) reported by AlignRT can be used as
      the gating parameter, with a recommended threshold of +/-3 mm and 5 mm,
      respectively. CONCLUSION: The RPM system alone may not be sufficient for the
      required level of accuracy in left-sided breast/CW DIBH treatments. The 3D
      surface imaging can be used to ensure patient setup and monitor inter- and intra-
      fractional motions. Furthermore, the target position accuracy during DIBH
      treatment can be improved by AlignRT as a superior surrogate, in addition to the
      RPM system.

PMID- 24853146
TI  - Deblurring algorithms accounting for the finite detector size in photoacoustic
      tomography.
AB  - Most reconstruction algorithms for photoacoustic tomography, like back projection
      or time reversal, work ideally for point-like detectors. For real detectors,
      which integrate the pressure over their finite size, images reconstructed by
      these algorithms show some blurring. Iterative reconstruction algorithms using an
      imaging matrix can take the finite size of real detectors directly into account,
      but the numerical effort is significantly higher compared to the use of direct
      algorithms. For spherical or cylindrical detection surfaces, the blurring caused
      by a finite detector size is proportional to the distance from the rotation
      center (spin blur) and is equal to the detector size at the detection surface. In
      this work, we apply deconvolution algorithms to reduce this type of blurring on
      simulated and on experimental data. Two particular deconvolution methods are
      compared, which both utilize the fact that a representation of the blurred image
      in polar coordinates decouples pixels at different radii from the rotation
      center. Experimental data have been obtained with a flat, rectangular
      piezoelectric detector measuring signals around a plastisol cylinder containing
      various small photoacoustic sources with variable distance from the center. Both
      simulated and experimental results demonstrate a nearly complete elimination of
      spin blur.

PMID- 24853147
TI  - Cervical cancer detection by time-resolved spectra of blood components.
AB  - Fluorescence spectral techniques are very sensitive, and hence they are gaining
      importance in cancer detection. The biomarkers indicative of cancer could be
      identified and quantified by spectral or time domain fluorescence spectroscopy.
      The results of an investigation of time-resolved spectra of cellular components
      of blood obtained from cervical cancer patients and normal controls are given.
      The cancer indicative biomarker in this paper is porphyrin; it has a fluorescence
      decay time of 60% more in samples of cancer patients than those of normal
      controls. Based on such measurements, a randomized set comprising samples from
      cancer patients and controls (N=27 in total) could be classified with sensitivity
      (92%) and specificity (86%).

PMID- 24853148
TI  - The deception of alcohol.

PMID- 24853149
TI  - Reinforcing the PA brand.

PMID- 24853150
TI  - Marathon Monday--a reflection.

PMID- 24853152
TI  - When communication fails: resolving end-of-life impasses.
AB  - Various protocols and advance directives can prepare physician assistants for
      difficult conversations with patients about end-of-life care. This case scenario
      explores the roles and influences that complicated one patient's care and how the
      situation was resolved.

PMID- 24853153
TI  - Three common ophthalmic emergencies.
AB  - Vision changes and ophthalmic complaints may represent potentially serious,
      sometimes fatal, systemic illnesses. This article summarizes the presenting signs
      and symptoms of retinal artery occlusion, giant cell arteritis, and oculomotor
      nerve palsy. 

PMID- 24853154
TI  - Liver transplantation in a critically ill patient.
AB  - The United Network for Organ Sharing recently changed its policies for liver
      allocation to give patients with severe hepatic failure priority due to their
      greater risk of morbidity and mortality. This case illustrates the benefit of
      transplant in critically ill patients. 

PMID- 24853155
TI  - Understanding the AHA/ACC's new cholesterol treatment guidelines.

PMID- 24853156
TI  - Exenatide extended-release: a once-weekly option for patients with type 2
      diabetes.
AB  - Exenatide extended-release is a new long-acting glucagon-like peptide-1 agonist
      that may be an attractive option for patients desiring to lose weight, who are
      prone to hypoglycemic episodes, and who have not achieved desired glycemic
      control with current therapy. 

PMID- 24853157
TI  - Lyme disease.

PMID- 24853158
TI  - Adult epiglottitis complicated by negative pressure pulmonary edema.

PMID- 24853159
TI  - Quality-switched laser tattoo removal.
AB  - Quality-switched (Q-switched) laser is the most effective method to remove
      tattoos with minimal adverse outcomes. This article reviews the types of tattoos
      commonly treated with Q-switched lasers, mechanisms behind the procedure,
      technologies used, patient considerations and contraindications, addressing
      patient expectations, treatment procedures, possible adverse reactions, and
      future techniques and technology.

PMID- 24853162
TI  - Something old, something new.

PMID- 24853161
TI  - Abdominal distension and upper extremity muscle wasting in a 59-year-old woman.

PMID- 24853163
TI  - Comparison of parameter threshold combinations for diffusion tensor tractography
      in chronic stroke patients and healthy subjects.
AB  - BACKGROUND: Although quantitative evaluation of diffusion tensor imaging (DTI)
      data seemed to be extremely important for clinical research its application is
      under debate. Besides fractional anisotropy (FA) the quantitative comparison
      between hemispheres of the number of fibers reconstructed by means of diffusion
      tensor tractography (DTT) is commonly used. However, the tractography-related
      parameters FA, minimum tract length (LENGTH) and the angle between two contiguous
      tracking steps (ANGLE) are inconsistently applied. Using 18 combinations we
      tested for the influence of parameter thresholds on the amount of reconstructed
      fibers for the posterior pyramidal tract in both hemispheres in order to obtain
      meaningful thresholds for DTT. RESULTS: In 14 chronic stroke patients with
      unilateral lesions of the pyramidal tract around the height of the internal
      capsule and considerable motor deficits a 3-way repeated-measures ANOVA showed a
      significant interaction between the effects of FA and ANGLE level on
      reconstructed fiber lateralization, F (2.9, 37.67) = 3.01, p = 0.044, and a
      significant main effect FA, F (1.4, 18.1) = 11.58, p = 0.001. Post-hoc pairwise
      comparisons showed that this interaction was completely driven by FA. In 22 right
      handed healthy subjects no significant interactions or main effects could be
      found. CONCLUSION: The parameter threshold combinations with highest FA showed
      highest effect. ANGLE and LENGTH insofar influenced the lateralization effect
      when selected as liberal as possible, short LENGTH and large ANGLE thresholds.
      The DTT approach should be used with great care since results are highly
      dependent on the thresholds applied.

PMID- 24853164
TI  - The relationship between migraine and infant colic: a systematic review and meta
      analysis.
AB  - CONTEXT: Infant colic is a common and distressing disorder of early infancy. Its
      etiology is unknown, making treatment challenging. Several articles have
      suggested a link to migraine. OBJECTIVE: The objective of this article was to
      perform a systematic review and, if appropriate, a meta-analysis of the studies
      on the relationship between infant colic and migraine. DATA SOURCES: Studies were
      identified by searching PubMed and ScienceDirect and by hand-searching references
      and conference proceedings. STUDY SELECTION: For the primary analysis, studies
      specifically designed to measure the association between colic and migraine were
      included. For the secondary analysis, studies that collected data on colic and
      migraine but were designed for another primary research question were also
      included. DATA EXTRACTION: Data were abstracted from the original studies,
      through communication with study authors, or both. Two authors independently
      abstracted data. MAIN OUTCOMES AND MEASURES: The main outcome measure was the
      association between infant colic and migraine using both a fixed-effects model
      and a more conservative random-effects model. RESULTS: Three studies were
      included in the primary analysis; the odds ratio for the association between
      migraine and infant colic was 6.5 (4.6-8.9, p < 0.001) for the fixed-effects
      model and 5.6 (3.3-9.5, p = 0.004) for the random-effects model. In a sensitivity
      analysis wherein the study with the largest effect size was removed, the odds
      ratio was 3.6 (95% CI 1.7-7.6, p = 0.001) for both the fixed-effects model and
      random-effects model. CONCLUSIONS: In this meta-analysis, infant colic was
      associated with increased odds of migraine. If infant colic is a migrainous
      disorder, this would have important implications for treatment. The main
      limitation of this meta-analysis was the relatively small number of studies
      included.

PMID- 24853165
TI  - Proton pump inhibitor-related headaches: a nationwide population-based case
      crossover study in Taiwan.
AB  - BACKGROUND: Headaches resulting from proton pump inhibitor (PPI) use could cause
      discontinuation of PPI in as many as 40% of patients who experience such
      headaches. Previous studies focusing on acute headache risk from PPI use are rare
      and limited to clinical trials of a single PPI. OBJECTIVES: To investigate the
      association between PPI use and headache with a nationwide population-based case
      crossover study. METHODS: Records containing the first diagnosis of any headache,
      including migraine and tension-type headaches, were retrieved from Taiwan
      National Health Insurance Database (1998-2010). We compared the rates of PPI use
      for cases and controls during time windows of 7, 14, and 28 days. The adjusted
      self-matched odds ratios (ORs) and 95% confidence intervals (CIs) from a
      conditional logistic regression model were used to determine the association
      between PPI use and headache. RESULTS: Overall, 314,210 patients with an initial
      diagnosis of any headache during the study period were enrolled. The adjusted ORs
      for headache risk after PPI exposure were calculated for three time periods
      (within 7 days=1.41, p=0.002, 95% CI 1.14-1.74; within 14 days=1.36, p<0.001, 95%
      CI 1.16-1.59; within 28 days=1.20, p=0.002, 95% CI 1.07-1.35). Subgroup analyses
      showed female patients had an increased risk of headache. Among PPIs,
      lansoprazole and esomeprazole had the highest risks of headache incidence, which
      were similar to that of nitrates. CONCLUSION: PPI usage is associated with an
      increased risk for acute headache. Female patients and use of lansoprazole or
      esomeprazole present the greatest risks of headache.

PMID- 24853167
TI  - Psychopathy: clinical features, developmental basis and therapeutic challenges.
AB  - WHAT IS KNOWN AND OBJECTIVE: Psychopathy is a personality disorder characterized
      by deficits in personality and behaviour. Personality deficits are marked by
      interpersonal and affective facets, including pathological lying, grandiose sense
      of self-worth, lack of remorse and callousness. Behavioural deficits are defined
      by lifestyle and antisocial deficits, including impulsivity, parasitic lifestyle
      and poor behavioural controls. The objective of this review is to provide
      clinicians with (i) an appreciation of the clinical features of psychopathy, (ii)
      an understanding of the structural and functional derangements and the genetic
      and environmental factors which serve as the basis for the development of
      psychopathy and (iii) a summary of published reports of pharmacological
      approaches to the management of this disorder. METHODS: A literature search of
      MEDLINE/PubMed (1966-present) was conducted using the MeSH search terms
      psychopathy and antisocial personality disorder alone and in combination with the
      subheading drug therapy. Additional databases included Web of Science (1945
      present) and International Pharmaceutical Abstracts (1970-present) using the text
      words psychopath and antisocial personality were searched. A search of Amazon
      books using the search terms psychopathy and sociopathy was also performed.
      Bibliographies of relevant articles were searched for additional citations. All
      data sources in English were considered for inclusion. For background
      information, broad subject headings were searched for review articles first.
      Human and animal drug therapy articles were evaluated giving preference to those
      papers using a controlled trial methodology. RESULTS AND DISCUSSION: Psychopathy
      is a personality disorder characterized by a lack of conscience, pathologic
      lying, manipulative behaviour and often superficial charm. The incidence of
      psychopathy in the general population is generally considered to be 0.6-4% with a
      higher proportion of males to females. Brain imaging studies of psychopaths
      suggest a smaller and less active amygdala and prefrontal cortex. There also
      appear to be physiological derangements in psychopathy, including
      alterations/dysregulation in neurotransmitter homeostasis (dopamine and
      serotonin), altered endocrine responses (testosterone and cortisol) and altered
      autonomic responses to emotional stimuli and stressors. Although both genetic and
      environmental factors likely contribute to the developmental basis of
      psychopathy, these factors are poorly understood at present. To date, limited
      studies with pharmacologic interventions in psychopathy are available and there
      are insufficient trials to determine efficacy. WHAT IS NEW AND CONCLUSION:
      Psychopathy is a serious personality disorder with profound negative effects on
      individuals and society. To design rational therapeutic strategies for this
      disorder, additional research is needed to discover the specific pathological and
      pathophysiological basis of psychopathy and to further elucidate the genetic and
      environmental factors responsible for psychopathic development. There is emerging
      evidence of phenotypic variants in psychopathy, including successful and
      unsuccessful types. It is important for clinicians to be cognizant of the
      psychopathic personality.

PMID- 24853166
TI  - Prevalence of neck pain in migraine and tension-type headache: a population
      study.
AB  - BACKGROUND: We assessed the prevalence of neck pain in the population in relation
      to headache. METHODS: In a cross-sectional study, a total of 797 individuals
      completed a headache interview and provided self-reported data on neck pain. We
      identified migraine, TTH or both migraine and TTH (M+TTH) groups. Pericranial
      tenderness was recorded in 496 individuals. A total tenderness score (TTS) was
      calculated as the sum of local scores with a maximum score of 48. RESULTS: The
      one-year prevalence of neck pain was 68.4% and higher in those with vs. without
      primary headache (85.7% vs. 56.7%; adjusted OR 3.0, 95% CI 2.0-4.4, p<0.001).
      Adjusting for age, gender, education and poor self-rated health, in comparison
      with those without headaches, the prevalence of neck pain (56.7%) was
      significantly higher in those with M+TTH (89.3%), pure TTH (88.4%) and pure
      migraine (76.2%) (p<0.05 for all three group comparisons). Individuals with neck
      pain had higher TTS than individuals without neck pain (15.1+/-10.5 vs. 8.4+/
      8.0, p<0.001). CONCLUSIONS: Neck pain is highly prevalent in the general
      population and even more prevalent in individuals with primary headaches.
      Prevalence is highest in coexistent M+TTH, followed by pure TTH and migraine.
      Myofascial tenderness is significantly increased in individuals with neck pain.

PMID- 24853168
TI  - Effect of the Interposition of Calcium Phosphate Materials on Tendon-Bone Healing
      During Repair of Chronic Rotator Cuff Tear.
AB  - BACKGROUND: The current nature of tendon-bone healing after rotator cuff (RC)
      repair is still the formation of granulation tissue at the tendon-bone interface
      rather than the formation of fibrocartilage, which is the crucial structure in
      native tendon insertion and can be observed after knee ligament reconstruction.
      The interposition of calcium phosphate materials has been found to be able to
      enhance tendon-bone healing in knee ligament reconstruction. However, whether the
      interposition of these kinds of materials can enhance tendon-bone healing or even
      change the current nature of tendon-bone healing after RC repair still needs to
      be explored. HYPOTHESIS: The interposition of calcium phosphate materials during
      RC repair would enhance tendon-bone healing or change its current nature of
      granulation tissue formation into a more favorable process. STUDY DESIGN:
      Controlled laboratory study. METHODS: A total of 144 male Sprague-Dawley rats
      underwent unilateral detachment of the supraspinatus tendon, followed by delayed
      repair after 3 weeks. The animals were allocated into 1 of 3 groups: (1) repair
      alone, (2) repair with Ca5(PO4)2SiO4 (CPS) bioceramic interposition, or (3)
      repair with hydroxyapatite (HA) bioceramic interposition at the tendon-bone
      interface. Animals were sacrificed at 2, 4, or 8 weeks postoperatively, and
      microcomputed tomography (micro-CT) was used to quantify the new bone formation
      at the repair site. New fibrocartilage formation and collagen organization at the
      tendon-bone interface was evaluated by histomorphometric analysis. Biomechanical
      testing of the supraspinatus tendon-bone complex was performed. Statistical
      analysis was performed using 1-way analysis of variance. Significance was set at
      P < .05. RESULTS: The micro-CT analysis demonstrated remarkable osteogenic
      activity and osteoconductivity to promote new bone formation and ingrowth of CPS
      and HA bioceramic, with CPS bioceramic showing better results than HA.
      Histological observations indicated that CPS bioceramic had excellent
      biocompatibility and biodegradability. At early time points after the RC repair,
      CPS bioceramic significantly increased the area of fibrocartilage at the tendon
      bone interface compared with the control and HA groups. Moreover, CPS and HA
      bioceramics had significantly improved collagen organization. Biomechanical tests
      indicated that the CPS and HA groups have greater ultimate load to failure and
      stiffness than the control group at 4 and 8 weeks, and the CPS specimens
      exhibited the maximum ultimate load to failure, stiffness, and stress of the
      healing enthesis. CONCLUSION: Both CPS and HA bioceramics aid in cell attachment
      and proliferation and accelerate new bone formation, and CPS bioceramic has a
      more prominent effect on tendon-to-bone healing. CLINICAL RELEVANCE: Local
      application of CPS and HA bioceramic at the tendon-bone interface shows promise
      in improving healing after rotator cuff tear repair.

PMID- 24853170
TI  - Implant-Supported Single Crowns Replacing Congenitally Missing Maxillary Lateral
      Incisors: A 5-Year Follow-Up.
AB  - BACKGROUND: Knowledge of the long-term survival of single implants in cases of
      congenitally missing lateral incisors in the maxilla is limited. PURPOSE: This
      retrospective study aimed to evaluate the 5-year survival of implants and implant
      supported crowns (ISCs) and to assess the functional and aesthetic outcomes from
      the professional and patient perspectives. MATERIALS AND METHODS: From a total of
      46 patients with congenitally missing upper lateral incisors, 36 patients treated
      with 54 Branemark(r) (Nobel Biocare AB, Goteborg, Sweden) implants and ISCs
      participated in the study. A clinical examination, California Dental Association
      (CDA) evaluation, and patient questionnaire were used to rate and compare the
      objective and subjective evaluations of the ISCs. RESULTS: The survival of
      implants and ISCs was 100%. The CDA ratings were satisfactory for all ISCs, with
      70% being rated excellent. The patient rating was also high for the overall
      satisfaction item, with 21 being completely satisfied and 14 fairly satisfied.
      However, 12 patients wished for the replacement of their ISCs. Logistic
      regression analysis indicated that a less optimal embrasure fill was the most
      discriminating factor though not statistically significant (p = .082).
      CONCLUSIONS: One-third of the patients wished for the replacement of their ISCs.
      Soft tissue adaptation seems to be an important factor for overall satisfaction.

PMID- 24853169
TI  - Population pharmacokinetic study of benznidazole in pediatric Chagas disease
      suggests efficacy despite lower plasma concentrations than in adults.
AB  - INTRODUCTION: Chagas disease, caused by the parasite Trypanosoma cruzi, can lead
      to long term cardiac morbidity. Treatment of children with benznidazole is
      effective, but no pediatric pharmacokinetics data are available and clinical
      pharmacology information on the drug is scarce. PATIENTS AND METHODS: Prospective
      population pharmacokinetic (PK) cohort study in children 2-12 years old with
      Chagas disease treated with oral benznidazole 5-8 mg/kg/day BID for 60 days.
      (clinicaltrials.gov #NCT00699387). RESULTS: Forty children were enrolled in the
      study. Mean age was 7.3 years. A total of 117 samples were obtained from 38
      patients for PK analysis. A one compartment model best fit the data. Weight
      corrected clearance rate (CL/F) showed a good correlation with age, with younger
      patients having a significantly higher CL/F than older children and adults.
      Simulated median steady-state benznidazole concentrations, based on model
      parameters, were lower for children in our study than for adults and lowest for
      children under 7 years of age. Treatment was efficacious in the 37 patients who
      completed the treatment course, and well tolerated, with few, and mild, adverse
      drug reactions (ADRs). DISCUSSION: Observed benznidazole plasma concentrations in
      children were markedly lower than those previously reported in adults (treated
      with comparable mg/kg doses), possibly due to a higher CL/F in smaller children.
      These lower blood concentrations were nevertheless associated to a high
      therapeutic response in our cohort. Unlike adults, children have few adverse
      reactions to the drug, suggesting that there may be a direct correlation between
      drug concentrations and incidence of ADRs. Our results suggest that studies with
      lower doses in adults may be warranted. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT00699387.

PMID- 24853171
TI  - Development and validation of a theoretical test in endosonography for pulmonary
      diseases.
AB  - BACKGROUND: Theoretical testing provides the necessary foundation to perform
      technical skills. Additionally, testing improves the retention of knowledge.
      OBJECTIVES: The aims of this study were to develop a multiple-choice test in
      endosonography for pulmonary diseases and to gather validity evidence for this
      test. METHODS: Initially, 78 questions were constructed after informal
      conversational interviews with 4 international experts in endosonography. The
      clarity and content validity of the questions were tested using a Delphi-like
      approach. Construct validity was explored by administering the test to 3 groups
      with different levels of endosonography experience: 27 medical students, 18
      respiratory physicians with limited endosonography experience, and 14 experts in
      endosonography. RESULTS: Two Delphi iterations reduced the test to 52 questions.
      After item analysis, the final test consisted of 46 questions with a mean item
      discrimination of 0.47 and a mean item difficulty of 0.63. The internal
      consistency reliability was calculated at 0.91. The 3 groups performed
      significantly differently (ANOVA: p < 0.001), and post hoc tests were
      significant. The experts performed significantly more consistently than the
      novices (p = 0.037) and the intermediates (p < 0.001). CONCLUSIONS: This study
      provides a theoretical test in endosonography consisting of multiple-choice
      questions. Validity evidence was gathered, and the test demonstrated content and
      construct validity.

PMID- 24853173
TI  - Validation of a computational docking methodology to identify the non-covalent
      binding site of ligands to DNA.
AB  - Despite the biomedical consequences of carcinogen-DNA interactions and the
      potential of DNA as a drug target in medicinal chemistry, only a small number of
      studies have validated or used docking methods for the prediction of the physical
      binding of small molecules to DNA. Knowledge of the DNA-physically-bound ligand
      geometry can lead to the elucidation of the molecular-level mechanism of drugs as
      well as predicting the subsequent chemical interactions that lead to DNA damage
      from carcinogens. We sought to validate AutoDock 4.2, a docking method that
      includes a physics-based free energy function and a Lamarckian Genetic Algorithm,
      for the prediction of ligand geometries upon physical binding to DNA. We
      performed simulations by systematically changing the length of the search process
      for a comprehensive set of 32 ligand-DNA molecular systems with different physico
      chemical properties, and we used a free-energy-based convergence criterion to
      terminate our simulations. For 11 out of 28 molecular systems for which
      convergence was achieved, the lowest binding free energy geometries were within 2
      A of the experimentally determined geometry. Considering all predicted sites with
      free energy changes within 20% of the lowest binding free energy site, we found a
      site within 2 A of the experimentally determined geometry for 24 out of the 28
      systems. However, the predicted hydrogen bonding interactions were different for
      most molecular systems compared to the same interactions in the experimentally
      determined geometry. We discuss reasons for the successes and failures,
      implications, and the importance of ensuring an adequate search in docking
      calculations. Overall, we concluded that AutoDock 4.2 can be used to predict the
      non-covalent binding geometry of a small molecule to DNA with some limitations. 

PMID- 24853174
TI  - Engineering three-dimensionally electrodeposited Si-on-Ni inverse opal structure
      for high volumetric capacity Li-ion microbattery anode.
AB  - Aiming at improving the volumetric capacity of nanostructured Li-ion battery
      anode, an electrodeposited Si-on-Ni inverse opal structure has been proposed in
      the present work. This type of electrode provides three-dimensional bi-continuous
      pathways for ion/electron transport and high surface area-to-volume ratios, and
      thus exhibits lower interfacial resistance, but higher effective Li ions
      diffusion coefficients, when compared to the Si-on-Ni nanocable array electrode
      of the same active material mass. As a result, improved volumetric capacities and
      rate capabilities have been demonstrated in the Si-on-Ni inverse opal anode. We
      also show that optimization of the volumetric capacities and the rate performance
      of the inverse opal electrode can be realized by manipulating the pore size of
      the Ni scaffold and the thickness of the Si deposit. 

PMID- 24853175
TI  - High level of HSF1 associates with aggressive endometrial carcinoma and suggests
      potential for HSP90 inhibitors.
AB  - BACKGROUND: Recent identification of a specific role of HSF1 in cancer
      progression has led to new relevance of HSF1 as both a prognostic and a
      predictive marker. The role of HSF1 in endometrial cancer has so far been
      unexplored. METHODS: A total of 823 lesions from endometrial carcinoma
      precursors, primary tumours and metastases were prospectively collected and
      explored for HSF1 protein expression in relation to established markers for
      aggressive disease and survival. Transcriptional alterations related to HSF1
      protein level were investigated by microarray analysis for 224 freshly frozen
      samples in parallel. RESULTS: High expression of HSF1 protein in endometrial
      carcinoma is significantly associated with aggressive disease and poor survival
      (all P-values <= 0.02), also among ERalpha-positive patients presumed to have
      good prognosis. The HSF1-related gene signatures increase during disease
      progression and were also found to have prognostic value. Gene expression
      analyses identified HSP90 inhibition as a potential novel therapeutic approach
      for cases with high protein expression of HSF1. CONCLUSIONS: We demonstrate for
      the first time in endometrial cancer that high expression of HSF1 and measures
      for transcriptional activation of HSF1 associate with poor outcome and disease
      progression. The HSP90 inhibitors are suggested as new targeted therapeutics for
      patients with high HSF1 levels in tumour in particular.

PMID- 24853176
TI  - MGMT promoter hypermethylation and K-RAS, PTEN and TP53 mutations in tamoxifen
      exposed and non-exposed endometrial cancer cases.
AB  - BACKGROUND: Tamoxifen has anti-oestrogenic and anti-tumour activity in the
      breast, but is oestrogenic and carcinogenic in the endometrium. It can induce
      experimental tumours by both hormonal and DNA-damaging mechanisms, but its
      carcinogenic mode of action in human endometrium remains unclear. METHODS: We
      investigated whether an epigenetic mechanism, involving promoter hypermethylation
      of the gene for the DNA repair enzyme MGMT (O6-methylguanine DNA
      methyltransferase), was associated with K-RAS, TP53 and PTEN mutations in
      endometrial tumours from women treated with tamoxifen (TAM, n=30) or unexposed to
      the drug (EC, n=38). RESULTS: There were significant (P<0.05) differences in
      tumour grade between the TAM and EC groups, with more favourable morphology in
      the latter. K-RAS mutations, predominantly G>A, occurred in small numbers in both
      groups. TP53 mutations were of mainly A>G, C>T and indel modifications in both
      groups, but more frequent in TAM cases. PTEN mutations dominated in EC tumours
      and were of the type that has large impact on protein function, such as indel or
      nonsense mutations. These observations alongside the mutational spectrum in PTEN
      suggest that the malignancies arise from different backgrounds, hence pointing to
      an effect of tamoxifen. Both groups displayed MGMT promoter hypermethylation.
      This coincided with mutations more frequently in the TAM (78%) than in the EC
      (50%) group, even though there were significantly (P<0.05) fewer mutations and
      methylations in TAM cases. CONCLUSIONS: Although the difference in coincidence
      did not reach significance with the current sample size, the findings suggest
      that epigenetic processes may play a role in the way tamoxifen induces
      endometrial cancer.

PMID- 24853177
TI  - The impact of life tables adjusted for smoking on the socio-economic difference
      in net survival for laryngeal and lung cancer.
AB  - BACKGROUND: Net survival is a key measure in cancer control, but estimates for
      cancers that are strongly associated with smoking may be biased. General
      population life tables represent background mortality in net survival, but may
      not adequately reflect the higher mortality experienced by smokers. METHODS: Life
      tables adjusted for smoking were developed, and their impact on net survival and
      inequalities in net survival for laryngeal and lung cancers was examined.
      RESULTS: The 5-year net survival estimated with smoking-adjusted life tables was
      consistently higher than the survival estimated with unadjusted life tables: 7%
      higher for laryngeal cancer and 1.5% higher for lung cancer. The impact of using
      smoking-adjusted life tables was more pronounced in affluent patients; the
      deprivation gap in 5-year net survival for laryngeal cancer widened by 3%, from
      11% to 14%. CONCLUSIONS: Using smoking-adjusted life tables to estimate net
      survival has only a small impact on the deprivation gap in survival, even when
      inequalities are substantial. Adjusting for the higher, smoking-related
      background mortality did increase the estimates of net survival for all
      deprivation groups, and may be more important when measuring the public health
      impact of differences or changes in survival, such as avoidable deaths or crude
      probabilities of death.

PMID- 24853178
TI  - Prognostic role of FGFR1 amplification in early-stage non-small cell lung cancer.
AB  - BACKGROUND: Recently, fibroblast growth factor receptor 1 (FGFR1) was discovered
      in squamous cell carcinomas (SCC) of the lung with FGFR1 amplification described
      as a promising predictive marker for anti-FGFR inhibitor treatment. Only few data
      are available regarding prevalence, prognostic significance and clinico
      pathological characteristics of FGFR1-amplified and early-stage non-small cell
      lung carcinomas (NSCLC). We therefore investigated the FGFR1 gene status in a
      large number of well-characterised early-stage NSCLC. METHODS: FGFR1 gene status
      was evaluated using a commercially available fluorescent in situ hybridisation
      (FISH) probe on a tissue microarray (TMA). This TMA harbours 329 resected,
      formalin-fixed and paraffin-embedded, nodal-negative NSCLC with a UICC stage I
      II. The FISH results were correlated with clinico-pathological features and
      overall survival (OS). RESULTS: The prevalence of an FGFR1 amplification was
      12.5% (41/329) and was significantly (P<0.0001) higher in squamous cell carcinoma
      (SCC) (20.7%) than in adenocarcinoma (2.2%) and large cell carcinoma (13%).
      Multivariate analysis revealed significantly (P=0.0367) worse 5-year OS in
      patients with an FGFR1-amplified NSCLC. CONCLUSIONS: FGFR1 amplification is
      common in early-stage SCC of the lung and is an independent and adverse
      prognostic marker. Its potential role as a predictive marker for targeted
      therapies or adjuvant treatment needs further investigation.

PMID- 24853179
TI  - Tropomyosin-related receptor kinase B at the invasive front and tumour cell
      dedifferentiation in gastric cancer.
AB  - BACKGROUND: Tropomyosin-related receptor kinase B (TrkB) promotes proliferation
      and invasion, relating to poor prognosis of various malignancies. We examined the
      role of TrkB at the invasive front of gastric cancer (GC) and its association
      with tumour cell dedifferentiation and tumour budding. METHODS: Immunoreactive
      TrkB was evaluated at the tumour centre and margin using whole-tissue sections of
      320 GC patients. Tumour cell dedifferentiation was defined as higher histologic
      grade at the tumour margin than the surface or tumour centre. Tumour budding was
      also scored on cytokeratin-stained sections. RESULTS: Sixty-five patients (20%)
      showed higher TrkB expression at the invasive front (TrkB expression was higher
      at the tumour margin than tumour centre). It was significantly associated with
      several aggressive phenotypes in the full cohort (n=320). It showed a prognostic
      significance in test subgroup (n=98) and was identified as an independent
      prognostic factor (HR=2.09; 95% CI: 1.26-3.53) by multivariate analysis in
      validation subgroup (n=222). Twenty-one patients showed tumour cell
      dedifferentiation. In predominantly differentiated tumour, higher TrkB at the
      invasive front was significantly associated with tumour budding rather than
      tumour cell dedifferentiation. CONCLUSIONS: Assessment of immunoreactive TrkB at
      the invasive front by whole-tissue sections provides prognostic information for
      GC patients.

PMID- 24853181
TI  - Role of Fbxw7 in the maintenance of normal stem cells and cancer-initiating
      cells.
AB  - In addition to the properties of self-renewal and multipotency, stem cells are
      characterised by their distinct cell cycle status. Somatic stem cells are
      maintained in a quiescent state but switch reversibly from quiescence to
      proliferation as needed. On the other hand, embryonic stem cells and induced
      pluripotent stem cells proliferate rapidly until the induction of differentiation
      results in inhibition of cell cycle progression. Uncovering the mechanisms
      underlying cell cycle control in stem cells should thus provide insight into
      regulation of the balance between self-renewal and differentiation, a key goal of
      stem cell biology. Recent research has shown that cancer-initiating cells (CICs),
      a cell population with stem cell-like properties in cancer, are also quiescent,
      with this characteristic conferring resistance to anticancer therapies that
      target dividing cells. Elucidation of the mechanisms of CIC quiescence might
      therefore be expected to provide a basis for the eradication of cancer. This
      review summarises our current understanding of the role of F-box and WD40 repeat
      domain-containing 7 (Fbxw7), a key regulator of the cell cycle, in the
      maintenance of normal stem cells and CICs, as well as attempts to define future
      challenges in this field. 

PMID- 24853180
TI  - Long-term alcohol intake and risk of endometrial cancer in the Nurses' Health
      Study, 1980-2010.
AB  - BACKGROUND: Previous epidemiologic studies have shown inconsistent results for
      the association between alcohol intake and endometrial cancer risk. Most of the
      studies, however, assessed alcohol intake after cancer diagnosis, or measured
      alcohol intake at baseline only. METHODS: We prospectively examined the
      association between alcohol intake and endometrial cancer risk in the Nurses'
      Health Study with 68 067 female participants aged 34-59 years in 1980. Alcohol
      intake was measured several times with validated dietary questionnaires. We
      calculated cumulative average alcohol intake to represent long-term intakes of
      individual subjects. Using Cox proportional hazards models, we estimated
      incidence rate ratios (RRs) and 95% confidence intervals (CIs) for endometrial
      cancer risk after controlling for several risk factors simultaneously. RESULTS:
      We identified a total of 794 invasive endometrial adenocarcinoma from 1980 to
      2010. We found an inverse association among alcohol drinkers (multivariable
      RR=0.81; 95% CI: 0.68-0.96) compared with nondrinkers. Women with light alcohol
      intake of <5 g per day (~half drink per day) had a 22% lower risk of endometrial
      cancer (multivariable RR=0.78; 95% CI: 0.66-0.94). Higher intake of alcohol,
      however, did not provide additional benefits against endometrial cancer:
      multivariable RRs for 5-14.9 g (~1 drink), 15-29.9 g (~2 drinks), or >= 30 g (>=
      2 drinks) versus 0 g per day were 0.88, 0.83, and 0.78 (95% CI: 0.49-1.25),
      respectively. The lower risk among drinkers (~half drink per day) appeared to be
      stronger for obese women, but no significant interaction by body mass index was
      found. CONCLUSIONS: This study provides prospective evidence for an inverse
      association between light alcohol intake (~half drink per day) in the long term
      and endometrial cancer risk, but above that level no significant association was
      found.

PMID- 24853182
TI  - Cdc20 and securin overexpression predict short-term breast cancer survival.
AB  - BACKGROUND: Cdc20 is an essential component of cell division and responsible for
      anaphase initiation regulated by securin degradation. Cdc20 function is strongly
      regulated by the spindle assembly checkpoint to ensure the timely separation of
      sister chromatids and integrity of the genome. We present the first results on
      Cdc20 in a large clinical breast cancer material. METHODS: The study was based on
      445 breast cancer patients with up to 20 years of follow-up (mean 10.0 years).
      DNA content was determined by image cytometry on cell imprints, and Cdc20 and
      securin immunohistochemistry on tissue microarrays of breast cancer tissue.
      RESULTS: In our results, high Cdc20 and securin expression was associated with
      aneuploid DNA content. In prognostic analyses, high Cdc20 immunoexpression alone
      and in combination with high securin immunoexpression indicated aggressive course
      of disease and up to 6.8-fold (P<0.001) risk of breast cancer death.
      Particularly, high Cdc20 and securin immunoexpression identified a patient
      subgroup with extremely short, on average 2.4 years, breast cancer survival and
      triple-negative breast cancer (TNBC) subtype. CONCLUSIONS: We report for the
      first time the association of high Cdc20 and securin immunoexpression with
      extremely poor outcome of breast cancer patients. Our experience indicates that
      Cdc20 and securin are promising candidates for clinical applications in breast
      cancer prognostication, especially in the challenging prognostic decisions of
      TNBC.

PMID- 24853183
TI  - Multi-colour FISH in oesophageal adenocarcinoma-predictors of prognosis
      independent of stage and grade.
AB  - BACKGROUND: Oesophageal adenocarcinoma or Barrett's adenocarcinoma (EAC) is
      increasing in incidence and stratification of prognosis might improve disease
      management. Multi-colour fluorescence in situ hybridisation (FISH) investigating
      ERBB2, MYC, CDKN2A and ZNF217 has recently shown promising results for the
      diagnosis of dysplasia and cancer using cytological samples. METHODS: To identify
      markers of prognosis we targeted four selected gene loci using multi-colour FISH
      applied to a tissue microarray containing 130 EAC samples. Prognostic predictors
      (P1, P2, P3) based on genomic copy numbers of the four loci were statistically
      assessed to stratify patients according to overall survival in combination with
      clinical data. RESULTS: The best stratification into favourable and unfavourable
      prognoses was shown by P1, percentage of cells with less than two ZNF217 signals;
      P2, percentage of cells with fewer ERBB2- than ZNF217 signals; and P3, overall
      ratio of ERBB2-/ZNF217 signals. Median survival times for P1 were 32 vs 73
      months, 28 vs 73 months for P2; and 27 vs 65 months for P3. Regarding each tumour
      grade P2 subdivided patients into distinct prognostic groups independently within
      each grade, with different median survival times of at least 35 months.
      CONCLUSIONS: Cell signal number of the ERBB2 and ZNF217 loci showed independence
      from tumour stage and differentiation grade. The prognostic value of multi-colour
      FISH-assays is applicable to EAC and is superior to single markers.

PMID- 24853184
TI  - X-chromosome-linked inhibitor of apoptosis as a key factor for chemoresistance in
      clear cell carcinoma of the ovary.
AB  - BACKGROUND: X-chromosome-linked inhibitor of apoptosis (XIAP) is one of the anti
      apoptotic proteins leading to chemoresistance in several cancers. The aim of this
      study is to evaluate the impact of XIAP expression upon ovarian clear cell
      carcinoma (CCC) that has a platinum-resistant phenotype. METHODS: Tissue
      microarrays made from 90 CCC patients were analysed for immunohistochemical
      expression levels of XIAP, c-Met, p-Akt and Bcl-XL. In addition, CCC cell lines
      were evaluated whether XIAP silencing could modulate sensitivity to platinum
      agent in vitro. RESULTS: High XIAP expression was observed in 30 (33%) of 90 CCC
      cases, and was associated with c-Met (<0.01) and Bcl-XL (<0.01) expression. Cases
      with high XIAP expression had lower response rate to primary platinum-based
      chemotherapy (10% vs 65%, P=0.02). In stages II-IV tumours, high XIAP expression
      was related with worse progression-free survival (PFS, P=0.02). Furthermore, high
      XIAP expression was identified as an independent worse prognostic factor for PFS
      and overall survival. Finally, downregulation of XIAP using XIAP-specific small
      interfering RNA increased sensitivity to cisplatin in human cancer cells derived
      from CCC. CONCLUSIONS: X-chromosome-linked inhibitor of apoptosis expression was
      correlated with chemoresistance of primary chemotherapy, and identified as a
      prognostic marker for CCC. X-chromosome-linked inhibitor of apoptosis could be a
      candidate for new therapeutic target in CCC.

PMID- 24853185
TI  - Co-targeting the IGF system and HIF-1 inhibits migration and invasion by (triple
      negative) breast cancer cells.
AB  - BACKGROUND: Metastatic triple-negative breast cancer is mostly incurable, due to
      lack of suitable drug targets. The insulin-like growth factor (IGF) system could
      provide such a target, and IGF-1 receptor (IGF-1R)-directed agents are already
      available, but seem unable to control all the complexities of the system,
      including crosstalk with hypoxia-inducible pathways. METHODS: Migration of triple
      negative MDA-231 breast cancer cells and its modulation by IGFs, the IGF-1R
      inhibitor NVP-AEW541 and the IGF-2-sequestering monoclonal antibody MAB292 were
      assessed by the scratch wound healing and Boyden chamber assays; the effect of
      topotecan (inhibiting hypoxia-inducible factor-1 (HIF-1)) under hypoxia was also
      evaluated. Constitutive as well as drug-modulated levels of components of the IGF
      and HIF-1 pathways were evaluated by western blotting and qPCR. RESULTS: IGF
      induced migration of MDA-231 cells was not abrogated by the IGF-1R inhibitor NVP
      AEW541, whereas IGF-2 sequestration by MAB292 significantly reduced cell
      migration. Under hypoxia, topotecan was also effective, likely by reducing HIF-1
      induced IGF-2 release. Simultaneous targeting of IGF-1R and IGF-2 or HIF-1
      completely abolished cell migration. CONCLUSIONS: IR activation may account for
      the failure of NVP-AEW541 to suppress MDA-231 cell migration. Ligand-targeting
      compounds, or co-inhibition of the IGF and HIF-1 systems, may prevent activation
      of compensatory signalling, thereby providing a valuable addition to IGF-1R
      inhibitor-based therapies.

PMID- 24853188
TI  - Variations in the anatomical positioning of impacted mandibular wisdom teeth and
      their practical implications.
AB  - Surgical removal of impacted third molars is one of the most frequent procedures
      in oral surgery. Here, three-dimensional (3D) imaging is often used, yet its
      necessity is still being heavily debated. The aim of the study was to describe
      the variation in the anatomical positioning of third mandibular molars, and, by
      doing so, examine the necessity of 3D imaging. A retrospective case study was
      performed with the patients from an oral surgery department from January 2009 to
      February 2013. The primary focus of the study was on the spatial relationship to
      the mandibular canal, as well as angulation, root configuration, and
      developmental stage of the wisdom tooth. Descriptive statistics were calculated
      for these variables. A total of 1197 wisdom teeth in 699 patients were evaluated.
      46.7% exhibited direct contact to the mandibular canal, another 28.7% showed
      close proximity and 24.6% a measurable distance. In 29.0%, the mandibular canal
      was vestibular and in 23.8% lingual to the wisdom tooth. In 7.4%, it was
      interradicular and in 0.6% intraradicular. Most teeth had one (21.3%) or two
      (55.3%) roots. Others had three (17.6%), four (2.0%) or five (0.2%) roots. In
      31.4% of the teeth, the root perforated the lingual compact bone, and in 4.3% the
      vestibular compact bone. 44.4% of the teeth had mesial angulation, 9.7% distal
      angulation, 35.3% lingual and 2.9% buccal angulation. Due to the anatomical
      variety, the use of 3D imaging is recommended before surgical removal of
      mandibular third molars if conventional imaging cannot exclude complicated
      conditions.

PMID- 24853186
TI  - Exogenous administration of protease-resistant, non-matrix-binding IGFBP-2
      inhibits tumour growth in a murine model of breast cancer.
AB  - BACKGROUND: Insulin-like growth factors (IGF-I and IGF-II) signal via the type 1
      IGF receptor (IGF-1R) and IGF-II also activates the insulin receptor isoform A
      (IR-A). Signalling via both receptors promotes tumour growth, survival and
      metastasis. In some instances IGF-II action via the IR-A also promotes resistance
      to anti-IGF-1R inhibitors. This study assessed the efficacy of two novel modified
      IGF-binding protein-2 (IGFBP-2) proteins that were designed to sequester both
      IGFs. The two modified IGFBP-2 proteins were either protease resistant alone or
      also lacked the ability to bind extracellular matrix (ECM). METHODS: The modified
      IGFBP-2 proteins were tested in vitro for their abilities to inhibit cancer cell
      proliferation and in vivo to inhibit MCF-7 breast tumour xenograft growth.
      RESULTS: Both mutants retained low nanomolar affinity for IGF-I and IGF-II (0.8
      2.1-fold lower than IGFBP-2) and inhibited cancer cell proliferation in vitro.
      However, the combined protease resistant, non-matrix-binding mutant was more
      effective in inhibiting MCF-7 tumour xenograft growth and led to inhibition of
      angiogenesis. CONCLUSIONS: By removing protease cleavage and matrix-binding
      sites, modified IGFBP-2 was effective in inhibiting tumour growth and reducing
      tumour angiogenesis.

PMID- 24853191
TI  - Surface extraction can provide a reference for micro-CT analysis of retrieved
      total knee implants.
AB  - BACKGROUND: Quantitative measurements of damage and wear in orthopaedic
      components retrieved from patients during revision surgery can provide valuable
      information. However, to perform these measurements there needs to be an estimate
      of the original, unworn geometry of the component, often requiring multiple scans
      of the various sizes of components that have been retrieved. The objective of
      this study was to determine whether the articular and backside surfaces could be
      independently segmented from a micro-CT reconstruction of a tibial insert, such
      that a tibial insert of one thickness could be used as a reference for a tibial
      insert of a different thickness. METHODS: New tibial inserts of a single width
      but with six different thicknesses were obtained and scanned with micro-CT. An
      automated method was developed to computationally segment the articular and
      backside surfaces of the components. Variability between intact and extracted
      components was determined. RESULTS: The deviations between the comparisons of the
      extracted surfaces (range, 0.0004 to 0.010 mm) were less (p<0.001) than the
      baseline deviation between the intact surfaces (range, 0.0002 to 0.053 mm).
      CONCLUSIONS: An extracted surface from one insert thickness could be used to
      accurately represent the surface of an insert of a different thickness. This
      greatly enhances the feasibility of performing retrieval studies using micro-CT
      as a quantitative tool, by reducing the costs and time associated with acquiring,
      scanning, and reconstructing multiple reference tibial insert geometries.
      CLINICAL RELEVANCE: This will add greater detail to studies of retrieved
      implants, to better establish how implants are functioning in vivo.

PMID- 24853187
TI  - Prevention of multidrug resistance (MDR) in osteosarcoma by NSC23925.
AB  - BACKGROUND: The major limitation to the success of chemotherapy in osteosarcoma
      is the development of multidrug resistance (MDR). Preventing the emergence of MDR
      during chemotherapy treatment has been a high priority of clinical and
      investigational oncology, but it remains an elusive goal. The NSC23925 has
      recently been identified as a novel and potent MDR reversal agent. However,
      whether NSC23925 can prevent the development of MDR in cancer is unknown.
      Therefore, this study aims to evaluate the effects of NSC23925 on prevention of
      the development of MDR in osteosarcoma. METHODS: Human osteosarcoma cell lines U
      2OS and Saos were exposed to increasing concentrations of paclitaxel alone or in
      combination with NSC23925 for 6 months. Cell sublines selected at different time
      points were evaluated for their drug sensitivity, drug transporter P-glycoprotein
      (Pgp) expression and activity. RESULTS: We observed that tumour cells selected
      with increasing concentrations of paclitaxel alone developed MDR with resistance
      to paclitaxel and other Pgp substrates, whereas cells cultured with paclitaxel
      NSC23925 did not develop MDR and cells remained sensitive to chemotherapeutic
      agents. Paclitaxel-resistant cells showed high expression and activity of the
      Pgp, whereas paclitaxel-NSC23925-treated cells did not express Pgp. No changes in
      IC50 and Pgp expression and activity were observed in cells grown with the
      NSC23925 alone. CONCLUSIONS: Our findings suggest that NSC23925 may prevent the
      development of MDR by specifically preventing the overexpression of Pgp. Given
      the significant incidence of MDR in osteosarcoma and the lack of effective agents
      for prevention of MDR, NSC23925 and derivatives hold the potential to improve the
      outcome of cancer patients with poor prognosis due to drug resistance.

PMID- 24853192
TI  - A deformation mechanism of hard metal surrounded by soft metal during roll
      forming.
AB  - It is interesting to imagine what would happen when a mixture of soft-boiled eggs
      and stones is deformed together. A foil made of pure Ti is stronger than that
      made of Cu. When a composite Cu/Ti foil deforms, the harder Ti will penetrate
      into the softer Cu in the convex shapes according to previously reported results.
      In this paper, we describe the fabrication of multilayer Cu/Ti foils by the roll
      bonding technique and report our observations. The experimental results lead us
      to propose a new deformation mechanism for a hard metal surrounded by a soft
      metal during rolling of a laminated foil, particularly when the thickness of hard
      metal foil (Ti, 25 MUm) is much less than that of the soft metal foil (Cu, 300
      MUm). Transmission Electron Microscope (TEM) imaging results show that the hard
      metal penetrates into the soft metal in the form of concave protrusions. Finite
      element simulations of the rolling process of a Cu/Ti/Cu composite foil are
      described. Finally, we focus on an analysis of the deformation mechanism of Ti
      foils and its effects on grain refinement, and propose a grain refinement
      mechanism from the inside to the outside of the laminates during rolling. 

PMID- 24853194
TI  - Radiation therapy for chemotherapy-resistant recurrent epithelial ovarian cancer.
AB  - OBJECTIVES: While radiation therapy is administered as a palliative treatment for
      recurrent ovarian cancer, it remains unclear whether it improves the prognosis.
      METHODS: The effects and adverse events of radiation therapy for patients with
      recurrent epithelial ovarian cancer were investigated using medical records.
      RESULTS: Herein, 46 subjects comprising 33 patients whose recurrent lesions were
      contained within the irradiation field (therapeutic radiation group; TRG) and 13
      patients with some recurrent lesions outside the irradiation field (palliative
      radiation group; PRG) were included. The TRG achieved a response rate (RR) of
      66%, a disease control rate (DCR) of 100%, a progression-free survival (PFS) of
      10 months, and an overall survival (OS) of 20 months. The PFS after radiation
      therapy was significantly longer than that following chemotherapy received just
      before radiation therapy. The PFS of patients with recurrent intrapelvic lesions
      was longer than that of patients with some extrapelvic recurrence. There was no
      significant association between PFS after radiation therapy and the duration from
      the previous chemotherapy or histological type. The RR, DCR, PFS, and OS of the
      PRG were 30 and 90% and 2 and 6 months, respectively. Serious adverse events were
      rare. CONCLUSIONS: Radiation therapy is a potential option for chemotherapy
      resistant, localized recurrent ovarian cancer. (c) 2014 S. Karger AG, Basel.

PMID- 24853195
TI  - Use of a machine learning algorithm to classify expertise: analysis of hand
      motion patterns during a simulated surgical task.
AB  - PURPOSE: To test the hypothesis that machine learning algorithms increase the
      predictive power to classify surgical expertise using surgeons' hand motion
      patterns. METHOD: In 2012 at the University of North Carolina at Chapel Hill, 14
      surgical attendings and 10 first- and second-year surgical residents each
      performed two bench model venous anastomoses. During the simulated tasks, the
      participants wore an inertial measurement unit on the dorsum of their dominant
      (right) hand to capture their hand motion patterns. The pattern from each bench
      model task performed was preprocessed into a symbolic time series and labeled as
      expert (attending) or novice (resident). The labeled hand motion patterns were
      processed and used to train a Support Vector Machine (SVM) classification
      algorithm. The trained algorithm was then tested for discriminative/predictive
      power against unlabeled (blinded) hand motion patterns from tasks not used in the
      training. The Lempel-Ziv (LZ) complexity metric was also measured from each hand
      motion pattern, with an optimal threshold calculated to separately classify the
      patterns. RESULTS: The LZ metric classified unlabeled (blinded) hand motion
      patterns into expert and novice groups with an accuracy of 70% (sensitivity 64%,
      specificity 80%). The SVM algorithm had an accuracy of 83% (sensitivity 86%,
      specificity 80%). CONCLUSIONS: The results confirmed the hypothesis. The SVM
      algorithm increased the predictive power to classify blinded surgical hand motion
      patterns into expert versus novice groups. With further development, the system
      used in this study could become a viable tool for low-cost, objective assessment
      of procedural proficiency in a competency-based curriculum.

PMID- 24853193
TI  - Effect of intraperitoneal administered ginseng total saponins on hyperalgesia
      induced by repeated intramuscular injection of acidic saline in rats.
AB  - The aim of this study was to assess the antinociceptive activity of ginseng total
      saponins (GTS) on hyperalgesia induced by repeated intramuscular injections of
      acidic saline in rats and to examine the mechanisms involved. Rats were injected
      intraperitoneally with a 0.9% saline vehicle or various doses of GTS after the
      development of hyperalgesia. Rats were then injected with N-methyl-D-aspartate
      (NMDA) or naloxone 10 min before GTS injection. The mechanical withdrawal
      threshold (MWT) was assessed with von Frey filaments. The MWT was significantly
      increased after intraperitoneal injection of 100 mg/kg and 200 mg/kg of GTS when
      compared with the MWT after the development of hyperalgesia. Injection of GTS
      with NMDA showed a significant decrease in the MWT when compared with GTS
      injection. GTS showed an antinociceptive activity against chronic muscle-induced
      pain, and the effect of GTS may be mediated by NMDA.

PMID- 24853196
TI  - End-of-life and palliative care curricula in internal medicine clerkships: a
      report on the presence, value, and design of curricula as rated by clerkship
      directors.
AB  - PURPOSE: End-of-life and palliative care (EOL/PC) education is a necessary
      component of undergraduate medical education. The extent of EOL/PC education in
      internal medicine (IM) clerkships is unknown. The purpose of this national study
      was to investigate the presence of formal EOL/PC curricula within IM clerkships;
      the value placed by IM clerkship directors on this type of curricula; curricular
      design and implementation strategies; and related barriers and resources. METHOD:
      The Clerkship Directors in Internal Medicine conducted its annual survey of its
      institutional members in April 2012. The authors analyzed responses to survey
      items pertaining to formal EOL/PC curriculum and content using descriptive
      statistics. The authors used qualitative techniques to analyze free-text
      responses. RESULTS: The response rate was 77.0% (94/122). Of those responding,
      75.8% (69/91) believed such training should occur in the IM clerkship, and 43.6%
      (41/94) reported formal curricula in EOL/PC. Multiple instructional modalities
      were used to deliver this content, with the majority of programs dedicating four
      or more hours to the curriculum. Curricula covered a wide range of topics, and
      student assessment tools were varied. Most felt that students valued this
      education. The qualitative analysis revealed differences in the values clerkship
      directors placed on teaching EOL/PC within the IM clerkship. CONCLUSIONS:
      Although many IM clerkship directors have implemented formal curricula in EOL/PC,
      a substantial gap remains between those who have implemented and those who
      believe it belongs in the clerkship. Time, faculty, cost, and competing demands
      are the main barriers to implementation.

PMID- 24853197
TI  - How men can excel as mentors of women.
AB  - Most male professionals have more experience mentoring men than they do mentoring
      women, and their male mentees progress further than their female mentees. Yet, in
      academic medicine, men have few forums in which to discuss the gender-related
      issues that they encounter. To address the gender-related questions that commonly
      arise, the author of this commentary offers perspectives and recommendations,
      consolidated from over 25 years of experience leading career and talent
      development programs, to assist men in successfully mentoring women. Her
      recommendations are organized around three questions: (1) How do women's and
      men's experiences in mentoring relationships tend to differ? (2) What interferes
      with the accurate evaluation of women's skills? and (3) Is the current generation
      of female trainees still at a gender-related disadvantage? She argues that men's
      ability to effectively mentor women depends to a great extent on their
      understanding of the challenges that women disproportionately face in developing
      their careers. Mentors who are skilled in adapting to the gender-related needs of
      mentees will contribute to women's retention and development in academic
      medicine, enhance the leadership capacity of their organizations and the
      profession, and extend their own legacies. 

PMID- 24853198
TI  - Connecting the dots: interprofessional health education and delivery system
      redesign at the Veterans Health Administration.
AB  - Health systems around the United States are embracing new models of primary care
      using interprofessional team-based approaches in pursuit of better patient
      outcomes, higher levels of satisfaction among patients and providers, and
      improved overall value. Less often discussed are the implications of new models
      of care for health professions education, including education for physicians,
      nurse practitioners, physician assistants, and other professions engaged in
      primary care. Described here is the interaction between care transformation and
      redesign of health professions education at the largest integrated delivery
      system in the United States: the Veterans Health Administration (VA). Challenges
      and lessons learned are discussed in the context of a demonstration initiative,
      the VA Centers of Excellence in Primary Care Education. Five sites, involving VA
      medical centers and their academic affiliates in Boise, Cleveland, San Francisco,
      Seattle, and West Haven, introduced interprofessional primary care curricula for
      resident physicians and nurse practitioner students beginning in 2011.
      Implementation struggles largely revolved around the operational logistics and
      cultural disruption of integrating educational redesign for medicine and nursing
      and facilitating the interface between educational and clinical activities. To
      realize new models for interprofessional teaching, faculty, staff, and trainees
      must understand the histories, traditions, and program requirements across
      professions and experiment with new approaches to achieving a common goal. Key
      recommendations for redesign of health professions education revolve around
      strengthening the union between interprofessional learning, team-based practice,
      and high-value care. 

PMID- 24853199
TI  - The relationship between licensing examination performance and the outcomes of
      care by international medical school graduates.
AB  - PURPOSE: The Step 2 Clinical Knowledge (CK) examination of the United States
      Medical Licensing Examination sequence is a requirement for the certification of
      international medical graduates (IMGs) by the Educational Commission for Foreign
      Medical Graduates. An association between scores on the test and the quality of
      care later provided by those who take it is central to its use in certification
      and licensure. The purpose of this study was to determine whether there is a
      relationship between scores on Step 2 CK and patient outcomes for IMGs. METHOD:
      This is a retrospective observational study of the 60,958 hospitalizations from
      2003 to 2009 in Pennsylvania where the principal diagnosis was acute myocardial
      infarction or congestive heart failure and the attending physician (N = 2,525)
      was an IMG who had taken the Step 2 CK. The main measures were the three-digit
      scores on Step 2 CK and in-hospital mortality. RESULTS: After adjustment for
      severity of illness, physician characteristics, and hospital characteristics,
      performance on Step 2 CK had a statistically significant inverse relationship
      with mortality. Each additional point on the examination was associated with a
      0.2% (95% CI: 0.1%-0.4%) decrease in mortality. The size of the effect is
      noteworthy, with each standard deviation (roughly 20 points) equivalent to a 4%
      change in mortality risk. CONCLUSIONS: These findings provide evidence for the
      validity of Step 2 CK scores. Given the magnitude of its relationship with
      patient outcomes, the results support the use of the examination as an effective
      screening strategy for licensure.

PMID- 24853200
TI  - Characterization of a novel carbonic anhydrase from freshwater pearl mussel
      Hyriopsis cumingii and the expression profile of its transcript in response to
      environmental conditions.
AB  - Gene encoding for alpha-carbonic anhydrases (alpha-CAs) and their functions in
      fundamental metabolism and biomineralization are widely identified in mollusks.
      However, the transcriptional regulation of alpha-CA genes in response to various
      environmental conditions remains unknown. In the present study, we characterized
      a cDNA encoding for an alpha-CA (HcCA) from the freshwater pearl mussel Hyriopsis
      cumingii. The spatial and temporal expression patterns of HcCA indicate that this
      gene is mainly expressed in the mantle of juvenile mussels. The expression
      profile of HcCA under various environmental conditions reveals that the
      transcription of HcCA is significantly regulated by Ca(2+) concentration, water
      temperature, pH and air exposure. Our results suggest that HcCA is a crucial
      target gene by which the external environmental conditions affecting shell growth
      and pH homeostasis of H. cumingii.

PMID- 24853201
TI  - Novel frame shift mutations ('A' deletion) observed in exon 9 of Wilms' tumor
      (WT1) gene in a patient reported with glomerulosclerosis.
AB  - Wilms' tumor-suppressor gene-1 (WT1) is a transcription factor that contains four
      zinc-finger motifs at the C-terminus and plays a crucial role in kidney and gonad
      development. We have identified primitive glomeruloid formation using
      immunohistochemistry in a patient who was clinically diagnosed with a Wilms'
      tumor. In order to understand the involvement of mutations in the WT1 gene, the
      genomic DNA was isolated from peripheral blood of the patient (18/F). Exon 9 of
      the WT1 gene was amplified and sequenced. The obtained sequence was BLAST
      searched against the transcript variants (TV) of the WT1 gene. An amplified exon
      9 sequence of the WT1 gene showing similarity with exon 9 of TV-A, F and exon 10
      of TV-B, D and E with a deletion of single nucleotide 'A' causing frame shift in
      the 4th zinc finger domain of the WT1 protein resulted in Wilms' tumor condition.
      The deletion position is variable with different transcript variants and they are
      present at: for TV-A c.1592delA, p.468, for TV-F c.1053delA, p.259, for TV-B
      c.1643delA, p.485, for TV-D c.1652 delA, p.488, and for TV-E c.1095delA, p.273;
      all these variations resulted in frame shift mutation. In order to substantiate
      these results in silico analysis was carried out; the structural superimposition
      of wild type and mutant WT1 structures showed that the mutated region exhibited a
      different confirmation with RMSD of 1.759A. Therefore, these results conclusively
      explain the mutation in the WT1 gene that leads to structural changes
      contributing to glomerulosclerosis.

PMID- 24853204
TI  - Understanding intrinsically irreversible, non-Nernstian, two-electron redox
      processes: a combined experimental and computational study of the electrochemical
      activation of platinum(IV) antitumor prodrugs.
AB  - Six-coordinate Pt(IV)-complexes are prominent prodrug candidates for the
      treatment of various cancers where, upon two-electron reduction and loss of two
      axial ligands, they form more familiar, pharmacologically active four-coordinate
      Pt(II) drugs. A series of electrochemical experiments coupled with extensive
      density functional calculations has been employed to elucidate the mechanism for
      the two-electron reduction of Pt(IV)(NH3)2Cl2L2 to Pt(II)(NH3)2Cl2 (L = CH3COO(
      ), 1; L = CHCl2COO(-), 2; L = Cl(-), 3). A reliable estimate for the normal
      reduction potential E(o) is derived for the electrochemically irreversible Pt(IV)
      reduction and is compared directly to the quantum chemically calculated reduction
      potentials. The process of electron transfer and Pt-L bond cleavage is found to
      occur in a stepwise fashion, suggesting that a metastable six-coordinate Pt(III)
      intermediate is formed upon addition of a single electron, and the loss of both
      axial ligands is associated with the second electron transfer. The quantum
      chemically calculated reduction potentials are in excellent agreement with
      experimentally determined values that are notably more positive than peak
      potentials reported previously for 1-3. 

PMID- 24853202
TI  - The CCoAOMT1 gene from jute (Corchorus capsularis L.) is involved in lignin
      biosynthesis in Arabidopsis thaliana.
AB  - The Caffeoyl-CoA 3-O-methyltransferase (CCoAOMT) is a key enzyme in lignin
      biosynthesis in plants. In this study we cloned the full-length cDNA of the
      Caffeoyl-CoA 3-O-methyltransferase (CCoAOMT) gene from jute using homology clone
      (primers were designed according to the sequence of CCoAOMT gene of other
      plants), and a modified RACE technique, subsequently named "CcCCoAOMT1".
      Bioinformatic analyses showed that the gene is a member of the CCoAOMT gene
      family. Real-time PCR analysis revealed that the CcCCoAOMT1 gene is
      constitutively expressed in all tissues, and the expression level was greatest in
      stem, followed by stem bark, roots and leaves. In order to understand this gene's
      function, we transformed it into Arabidopsis thaliana; integration (one insertion
      site) was confirmed following PCR and southern hybridization. The over-expression
      of CcCCoAOMT1 in these transgenic A.thaliana plants resulted in increased plant
      height and silique length relative to non-transgenic plants. Perhaps the most
      important finding was that the transgenic Arabidopsis plants contained more
      lignin (20.44-21.26%) than did control plants (17.56%), clearly suggesting an
      important role of CcCCoAOMT1 gene in lignin biosynthesis. These data are
      important for the success of efforts to reduce jute lignin content (thereby
      increasing fiber quality) via CcCCoAOMT1 gene inhibition. 

PMID- 24853203
TI  - Identification of a functional element in the promoter of the silkworm (Bombyx
      mori) fat body-specific gene Bmlp3.
AB  - 30K proteins are a group of structurally related proteins that play important
      roles in the life cycle of the silkworm Bombyx mori and are largely synthesized
      and regulated in a time-dependent manner in the fat body. Little is known about
      the upstream regulatory elements associated with the genes encoding these
      proteins. In the present study, the promoter of Bmlp3, a fat body-specific gene
      encoding a 30K protein family member, was characterized by joining sequences
      containing the Bmlp3 promoter with various amounts of 5' upstream sequences to a
      luciferase reporter gene. The results indicated that the sequences from -150 to 
      250bp and -597 to -675bp upstream of the Bmlp3 transcription start site were
      necessary for high levels of luciferase activity. Further analysis showed that a
      21-bp sequence located between -230 and -250 was specifically recognized by
      nuclear factors from silkworm fat bodies and BmE cells, and could enhance
      luciferase reporter-gene expression 2.8-fold in BmE cells. This study provides
      new insights into the Bmlp3 promoter and contributes to the further clarification
      of the function and developmental regulation of Bmlp3.

PMID- 24853206
TI  - Effect of temperature on hypoxia tolerance and its underlying biochemical
      mechanism in two juvenile cyprinids exhibiting distinct hypoxia sensitivities.
AB  - It is increasingly important to investigate the effect of temperature on hypoxia
      tolerance in fish species, as worldwide hypoxia worsens with increases in global
      warming. We selected the hypoxia-tolerant crucian carp (Carassius carassius) and
      the hypoxia-sensitive Chinese bream (Parabramis pekinensis) as model fish and
      investigated their hypoxia tolerance based on the critical oxygen tension of the
      routine metabolic rate (MO2rout) (Pcrit), aquatic surface respiration (ASRcrit)
      and loss of equilibrium (LOEcrit) after two weeks of acclimation at either 10, 20
      or 30  degrees C. We also measured the tissue substrate (glycogen and glucose of
      muscle and liver) and lactate levels of both normoxia- and hypoxia-treated fish
      (post-LOE). Crucian carp exhibited significantly lower Pcrit and LOEcrit but not
      ASRcrit. Crucian carp possessed higher hypoxia tolerance, partially due to a
      higher tissue glycogen reserve, which provides cellular fuel under severe
      hypoxia, as well as higher lactate tolerance and clearance ability than Chinese
      bream. The hypoxia tolerance was maintained in crucian carp but was decreased in
      Chinese bream as the temperature increased. The difference between the two
      species is based on the greater recruitment of tissue glycogen, resulting in an
      increased level of cellular fuel during hypoxia in crucian carp than in Chinese
      bream. In addition, crucian carp possessed the greater liver lactate clearance
      capacity, and the smaller increase in the MO2rout at higher temperatures compared
      to Chinese bream. Furthermore, substrate shortage and decreased lactate tolerance
      at high temperatures in Chinese bream might also contribute to the difference in
      hypoxia tolerance between the two species.

PMID- 24853207
TI  - The J6JFH1 strain of hepatitis C virus infects human B-cells with low replication
      efficacy.
AB  - Abstract Hepatitis C virus (HCV) infection is a serious health problem worldwide
      that can lead to hepatocellular carcinoma or end-stage liver disease. Current
      treatment with pegylated interferon, ribavirin, and NS3/4A protease inhibitor
      would lead to a good prognosis in a large population of patients, but there is
      still no effective vaccine for HCV. HCV robustly infects hepatocytes in the
      liver. However, extrahepatic manifestations such as mixed cryoglobulinemia, a
      systemic immune complex-mediated disorder characterized by B-cell proliferation,
      which may evolve into overt B-cell non-Hodgkin's lymphoma, have been
      demonstrated. HCV-RNA is often found to be associated with peripheral blood
      lymphocytes, suggesting a possible interaction with peripheral blood mononuclear
      cells (PBMCs), especially B-cells with HCV. B-cell HCV infection was a matter of
      debate for a long time, and the new advance in HCV in vitro infectious systems
      suggest that exosome can transmit HCV genome to support "infection." We aimed to
      clarify the susceptibility of primary B-cells to HCV infection, and to study its
      functional effect. In this article, we found that the recombinant HCV J6JFH1
      strain could infect human B-cells isolated from the peripheral blood of normal
      volunteers by the detection of both HCV-negative-strand RNA by reverse
      transcription polymerase chain reaction, and NS5A protein. We also show the
      blocking of HCV replication by type I interferon after B-cell HCV infection.
      Although HCV replication in B-lymphocytes showed lower efficiency, in comparison
      with hepatocyte line (Huh7) cells, our results clearly demonstrate that human B
      lymphocytes without other non-B-cells can actually be infected with HCV, and that
      this interaction leads to the induction of B-cells' innate immune response, and
      change the response of these cells to apoptosis.

PMID- 24853205
TI  - A global non-coding RNA system modulates fission yeast protein levels in response
      to stress.
AB  - Non-coding RNAs (ncRNAs) are frequent and prevalent across the taxa. Although
      individual non-coding loci have been assigned a function, most are
      uncharacterized. Their global biological significance is unproven and remains
      controversial. Here we investigate the role played by ncRNAs in the stress
      response of Schizosaccharomyces pombe. We integrate global proteomics and RNA
      sequencing data to identify a systematic programme in which elevated antisense
      RNA arising both from ncRNAs and from 3'-overlapping convergent gene pairs is
      directly associated with substantial reductions in protein levels throughout the
      genome. We describe an extensive array of ncRNAs with trans associations that
      have the potential to influence multiple pathways. Deletion of one such locus
      reduces levels of atf1, a transcription factor downstream of the stress-activated
      mitogen-activated protein kinase (MAPK) pathway, and alters sensitivity to
      oxidative stress. These non-coding transcripts therefore regulate specific stress
      responses, adding unanticipated information-processing capacity to the MAPK
      signalling system. 

PMID- 24853208
TI  - Advancing the standard of cancer care in 2014.

PMID- 24853209
TI  - The Affordable Care Act: where are we now? An NCCN roundtable.
AB  - The Affordable Care Act (ACA) is a transformational event for health care in the
      United States, with multiple impacts on health care, the economy, and society.
      Oncologists and other health care providers are already experiencing many changes
      direct and indirect, anticipated and unanticipated. A distinguished and diverse
      panel assembled at the NCCN 19th Annual Conference to discuss the early phase of
      implementation of the ACA. The roundtable touched on early successes and
      stumbling blocks; the impact of the ACA on contemporary oncology practice and the
      new risk pool facing providers, payers, and patients; and some of the current and
      future challenges that lie ahead for all. 

PMID- 24853210
TI  - Genomic analysis of breast cancer heralds a changing treatment paradigm.
AB  - Deep genomic analysis in breast cancer and the identification of driver mutations
      will result in treatments based on molecular subtypes and pathways. Mutations not
      yet familiar to most oncologists will become part of the clinical oncology
      vernacular. Such discoveries will advance the concept of "biology first, not drug
      first," because molecular biology will drive drug development and clinical trial
      design involving small, molecularly defined subsets of patients, according to a
      presentation at the NCCN 19th Annual Conference. 

PMID- 24853211
TI  - Treatment of metastatic breast cancer.
AB  - Many newer agents in combination are being studied in the front-line treatment of
      women with HER2-positive metastatic breast cancer (MBC), but the story in the
      endocrine arena is more about the wise use of new strategies to overcome
      endocrine resistance, because no new antihormonal agents have been approved in
      the past decade. During his presentation at the NCCN 19th Annual Conference, Dr.
      William Gradishar explored what's new in the treatment of MBC, focusing primarily
      on enhancing the effect of endocrine therapy to overcome resistance with newer
      targeted agents such as everolimus, reevaluating the role of rebiopsy on disease
      progression and measuring circulating tumor cells as a surrogate of response to
      treatment, and reviewing the effective treatment regimens for HER2-positive
      disease. 

PMID- 24853212
TI  - Advances in the treatment of non-small cell lung cancer.
AB  - Clinical trial data continue to emerge on treatments in advanced non-small cell
      lung cancer (NSCLC), supporting the strategy that histology and molecular driver
      mutations should guide treatment selection. During her presentation at the NCCN
      19th Annual Conference, Dr. Leora Horn highlighted 3 specific areas in which the
      2014 NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for NSCLC
      focus attention: updates on the assortment of chemotherapy options, targeted
      therapies and how acquired resistance to epidermal growth factor receptor
      tyrosine kinase inhibitors appears to have become the catalyst of the development
      of newer-generations of agents, and the revisited role of newer immunotherapeutic
      options. 

PMID- 24853213
TI  - Point/Counterpoint: early detection of prostate cancer: do the benefits outweigh
      the consequences?
AB  - Few clinical issues have polarized the oncology community as much as screening
      for prostate cancer, with advocates of prostate-specific antigen (PSA) testing
      vocal on one side and skeptics just as vocal on the other. At the NCCN 19th
      Annual Conference, Dr. Peter R. Carroll and Dr. Andrew J. Vickers tackled the
      controversy surrounding early detection of prostate cancer, focusing attention on
      the randomized trial results at the heart of the matter; over-detection (the
      Achilles' heel of screening); and the rationale behind the new, streamlined 2014
      NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Prostate
      Cancer Early Detection, which emphasize selective early detection and treatment
      and are tightly aligned with the NCCN Guidelines for Prostate Cancer. 

PMID- 24853214
TI  - New developments in the treatment of castration-resistant prostate cancer.
AB  - During the past 4 years, a host of new agents have been approved for the
      treatment of patients with advanced prostate cancer. As a result, selecting the
      right agent for the right patient at the right time is a clinical challenge. At
      the NCCN 19th Annual Conference, Dr. Celestia Higano explored the rationale
      behind such therapeutic decisions and the supporting clinical trial data. She
      reviewed the different classes of therapeutic agents, from immunotherapy and
      hormonal therapies to chemotherapy and radioisotopes, and offered suggestions for
      the clinical scenarios in which they may be used most successfully. 

PMID- 24853215
TI  - NCCN roundtable: talking to children about cancer.
AB  - A roundtable presentation at the NCCN 19th Annual Conference focused on the
      child's experience when a parent has cancer and concluded that honest
      communication, appropriate to the child's age and temperament, is essential, and
      that oncology providers should institute programs that help families deal with
      the illness. 

PMID- 24853216
TI  - Optimizing surveillance and balancing evidence with patient expectations.
AB  - For most cancers, intensive posttreatment surveillance does not improve survival,
      but can induce anxiety in patients and may lead to unnecessary testing due to
      false-positive results. For colorectal cancer, more intensive surveillance,
      especially during the first few survivorship years, is warranted. For breast
      cancer, surveillance for second primary cancers with annual mammography is
      warranted. This may also be the case for non-small cell lung cancer. For other
      tumors, less routine surveillance testing can be recommended. 

PMID- 24853217
TI  - Agents make "preferred list" in metastatic melanoma.
AB  - The 2014 version of the NCCN Guidelines for Melanoma lists 6 preferred regimens,
      most with a category 1 recommendation, and 8 "other active regimens." Effective
      new agents include ipilimumab, a monoclonal anti-CTLA4 antibody, and agents
      targeted against mutated BRAF and MEK. Researchers are now focused on the optimal
      way to combine or sequence these agents, while exploring other new classes.

PMID- 24853218
TI  - Optimal treatment of unresectable nonmelanoma skin cancers.
AB  - Unlike in other types of cancer, in metastatic nonmelanoma, there are few
      dedicated oncologists to care for patients with unresectable skin cancers and
      little reliable clinical evidence to craft a therapeutic strategy. In his
      presentation at the NCCN 19th Annual Conference, Dr. Thomas Olencki offered a
      glimpse of some of the therapeutic regimens tried in the past for these rare skin
      cancers and briefly reviewed some of the more promising agents for advanced
      squamous cell, basal cell, and Merkel cell carcinomas, although the current
      evidence base is limited. 

PMID- 24853219
TI  - Targeted agents: management of dermatologic toxicities.
AB  - Epidermal growth factor receptor (EGFR) inhibitors are widely used in the
      treatment of many cancers, and the cutaneous toxicity profile associated with
      these agents has become prominent. In fact, dermatologic side effects have also
      been reported with other targeted agents, including both BRAF and mTOR
      inhibitors. During her presentation at the NCCN 19th Annual Conference, Dr.
      Barbara Burtness reviewed the array of skin complications caused by many targeted
      therapies, focusing on the more common culprits, the role of prophylactic versus
      reactive management strategies, the need to be attentive to potential infections,
      the importance of mastering local measures to improve quality of life and
      cosmetic issues, the therapeutic mainstays (oral and topical antibiotics and
      topical steroids), and the preference of improving these cutaneous complications
      over suspending anticancer treatment. 

PMID- 24853220
TI  - Guidelines for NHL: updates to the management of diffuse large B-cell lymphoma
      and new guidelines for primary cutaneous CD30+ T-cell lymphoproliferative
      disorders and T-cell large granular lymphocytic leukemia.
AB  - During his presentation at the NCCN 19th Annual Conference, Dr. Andrew D.
      Zelenetz reviewed the updates to the 2014 NCCN Clinical Practice Guidelines in
      Oncology (NCCN Guidelines) for Non-Hodgkin's Lymphomas. Dr. Zelenetz first
      discussed the updates for diffuse large B-cell lymphoma (DLBCL), focusing
      primarily on the emergence of MYC-positive DLBCL; the limited role of imaging in
      early-stage disease; new treatment options; the challenge of tumor heterogeneity;
      and the impact of cell of origin in the selection of future therapies. Then, on
      behalf of Dr. Steven Horwitz, Dr. Zelenetz presented the new guidelines for
      primary cutaneous CD30+ T-cell lymphoproliferative disorders and T-cell large
      granular lymphocytic leukemia. 

PMID- 24853221
TI  - Chronic lymphocytic leukemia: state of the art and beyond.
AB  - In the treatment of chronic lymphocytic leukemia (CLL), select genomic studies
      can assist in risk stratification of newly diagnosed patients. Chemoimmunotherapy
      targeting CD20 offers a survival advantage in symptomatic patients both with and
      without these high-risk genetic features, though patients with del(17p13.1) have
      poor outcomes and require specific intervention. Obinutuzumab plus chlorambucil
      is a treatment standard for untreated elderly patients and is superior to
      rituximab plus chlorambucil. In the setting of relapsed CLL, the new kinase
      inhibitors have the potential to completely change the treatment paradigm of CLL.

PMID- 24853222
TI  - Multiple myeloma: advances reported in 2013 are useful in the clinic.
AB  - Studies on multiple myeloma reported in 2013 offer support for maintenance after
      induction and consolidation in newly diagnosed patients eligible for
      transplantation and for continued lenalidomide in patients not eligible for
      transplantation. The newest available agents, carfilzomib and pomalidomide, are
      approved to treat relapsed/refractory myeloma, and in combination they produce
      impressive response rates and durability. On the horizon, new classes of agents
      promise even more impressive gains in remission and survival. 

PMID- 24853223
TI  - NCCN bone health task force: key recommendations.
AB  - For patients with advanced cancers involving bone, the standard of care for
      maintaining bone health is the use of antiresorptive therapies such as
      bisphosphonates, selective estrogen-receptor modulators, and denosumab. However,
      although long-term adverse events are rare and the risk-benefit ratio of these
      agents is usually markedly in favor of treatment, clinicians should be aware that
      they can occur. At the NCCN 19th Annual Conference, Dr. Azeez Farooki presented
      the key findings of the NCCN Bone Health Task Force, focusing on such topics as
      screening for osteoporosis; the controversial use of drug holidays from chronic
      bisphosphonate therapy; the provocative yet unclear story surrounding the
      potential anticancer benefits of antiresorptive agents; imaging for metastatic
      bone disease; and safety considerations linked to calcium supplements, vitamin D,
      and bone-strengthening agents. 

PMID- 24853224
TI  - Monitoring molecular response to tyrosine kinase therapy in chronic myelogenous
      leukemia.
AB  - The dramatic decline in mortality rates in chronic myelogenous leukemia (CML) is
      a direct result of the advent of tyrosine kinase inhibitors (TKIs) and the
      dawning of the targeted era. Although many patients experience long-term benefits
      from imatinib or related agents, problems with resistance and tolerance dampen
      the outcomes for many others. During his presentation at the NCCN 19th Annual
      Conference, Dr. Jerald Radich reviewed the ever-expanding menu of TKIs for CML
      and shared his thoughts on resolving the clinical questions regarding when to
      start which drugs, how to sequence the drugs, and how best to decide when to
      change the therapeutic tack. 

PMID- 24853225
TI  - Treatment strategies for myeloid growth factors and intravenous iron: when, what,
      and how?
AB  - Myeloid growth factors can reduce the risk of chemotherapy-induced neutropenia
      (CIN) and thus impact the survival of patients with cancer. Patients should be
      assessed for risk, taking into consideration patient-related risk factors and
      chemotherapy regimens. Patients stratified as having at least a 20% risk for CIN
      should be considered for prophylactic growth factors. The NCCN Guidelines for
      Myeloid Growth Factors provide category 1 recommendations for the daily use of
      filgrastim, tbo-filgrastim, and pegfilgrastim. Cancer-related anemia can be
      treated with erythropoiesis-stimulating agents, red blood cell transfusion, or
      intravenous iron. 

PMID- 24853226
TI  - NCCN guidelines for survivorship expanded to address two common conditions.
AB  - The NCCN Clinical Practice Guidelines in Oncology for Survivorship include a new
      section on cancer-associated cognitive impairment and an expanded section on
      adult cancer pain that more completely addresses chemotherapy-induced peripheral
      neuropathy. These additions to the guidelines are the result of increasing
      awareness that long-term cancer survivors struggle with many late effects. Both
      the assessment and the management of cognitive impairment still lack a strong
      evidence-based foundation. The management of peripheral neuropathy, including the
      use of anti-depressants and opioids, often in combination, is backed by data
      primarily derived from clinical trials performed for various types of peripheral
      neuropathy. 

PMID- 24853228
TI  - Common controversies in the management of gallbladder cancer.
AB  - Gallbladder cancer is a rare and lethal malignancy. Most patients are best served
      at high-volume centers of excellence, where they are likely to receive evidence
      based care derived from a multidisciplinary approach. Surgical resection is
      recommended for early-stage disease, whereas if the disease is unresectable, the
      treatment options include biliary drainage, gemcitabine-based combination
      chemotherapy, fluoropyrimidine chemoradiation, clinical trial enrollment, or best
      supportive care. While treatment by T-stage is straightforward in many cases, the
      debate regarding simple versus radical cholecystectomy is still active for
      patients with T1b disease. Other controversies exist over the necessity of
      resecting the bile duct and port sites, the extent of lymph node dissection and
      hepatic resections, and the value of resection for patients with jaundice. 

PMID- 24853227
TI  - NCCN increases the emphasis on genetic/familial high-risk assessment in
      colorectal cancer.
AB  - NCCN has developed new guidelines for the assessment of high-risk
      familial/genetic colorectal cancer, and has positioned these recommendations
      within the guidelines for detection, prevention, and risk reduction. The Panel
      recommends that all patients with colorectal cancer be screened for Lynch
      syndrome, which occurs in 1 of every 35 patients and is the most common form of
      hereditary colorectal cancer. Such screening could be universal so that all
      tumors are genetically tested, or screening could be restricted to patients under
      the age of 70 and those aged 70 and older who meet clinical criteria. 

PMID- 24853229
TI  - Don't neglect cultural diversity in oncology care.
AB  - The growing Hispanic population in the United States mandates the need for
      oncology providers to become more familiar with disease patterns and cultural
      belief systems that can impact cancer care. "Culturally competent care" should be
      the mandate of all providers. This comprises awareness of cultural differences,
      communication in a manner that the patient understands, and respect. 

PMID- 24853230
TI  - International adaptation and use of NCCN Guidelines.
AB  - The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) describe a
      continuum of cancer care in the United States, from initial diagnosis through
      treatment and referral to hospice beyond treatment. However, in many other
      countries, there are no regional or national clinical practice guidelines. In
      2008, the NCCN-MENA (Middle East and North Africa) project was launched to adapt
      the NCCN Guidelines to this part of the world. During their joint presentation at
      the NCCN 19th Annual Conference, Dr. Ali Bazarbachi and Dr. Andrew D. Zelenetz
      explored the modification process of NCCN Guidelines for MENA and shared examples
      of how it improved the care of patients with adult T-cell leukemia or lymphoma
      and younger patients with diffuse large B-cell lymphoma-regardless of where they
      live. 

PMID- 24853232
TI  - A photochromic supramolecular polymer based on bis-p-sulfonatocalix[4]arene
      recognition in aqueous solution.
AB  - A photochromic supramolecular polymer based on bis-p-sulfonatocalix[4]arene
      recognition with a dithienylethene derivative in aqueous solution was fabricated.
      The resultant polymer showed good photochromic behaviour with obvious colour
      switching and a morphology change under alternative UV/Vis light stimuli. 

PMID- 24853231
TI  - Seroprevalence of autoantibodies against brain antigens in health and disease.
AB  - OBJECTIVE: We previously reported an unexpectedly high seroprevalence (~10%) of N
      methyl-D-aspartate-receptor subunit-NR1 (NMDAR1) autoantibodies (AB) in healthy
      and neuropsychiatrically ill subjects (N = 2,817). This finding challenges an
      unambiguous causal relationship of serum AB with brain disease. To test whether
      similar results would be obtained for other brain antigen-directed AB previously
      connected with pathological conditions, we systematically screened serum samples
      of 4,236 individuals. METHODS: Serum samples of healthy (n = 1,703) versus
      neuropsychiatrically ill subjects (schizophrenia, affective disorders, stroke,
      Parkinson disease, amyotrophic lateral sclerosis, personality disorder; total n =
      2,533) were tested. For analysis based on indirect immunofluorescence, we used
      biochip mosaics of frozen brain sections (rat, monkey) and transfected HEK293
      cells expressing respective recombinant target antigens. RESULTS: Seroprevalence
      of all screened AB was comparable in healthy and ill individuals. None of them,
      however, reached the abundance of NMDAR1 AB (again ~10%; immunoglobulin [Ig] G
      ~1%). Appreciable frequency was noted for AB against amphiphysin (2.0%), ARHGAP26
      (1.3%), CASPR2 (0.9%), MOG (0.8%), GAD65 (0.5%), Ma2 (0.5%), Yo (0.4%), and Ma1
      (0.4%), with titers and Ig class distribution similar among groups. All other AB
      were found in <=0.1% of individuals (anti-AMPAR-1/2, AQP4, CV2, Tr/DNER, DPPX
      IF1, GABAR-B1/B2, GAD67, GLRA1b, GRM1, GRM5, Hu, LGl1, recoverin, Ri, ZIC4). The
      predominant Ig class depended on antigen location, with intracellular epitopes
      predisposing to IgG (chi-square = 218.91, p = 2.8 * 10(-48) ). INTERPRETATION: To
      conclude, the brain antigen-directed AB tested here are comparably detectable in
      healthy subjects and the disease groups studied here, thus questioning an upfront
      pathological role of these serum AB.

PMID- 24853233
TI  - Down-regulated MAC30 expression inhibits proliferation and mobility of human
      gastric cancer cells.
AB  - BACKGROUND: Gastric cancer is one of the most common cancers in the world.
      MAC30/Transmembrane protein 97 (TMEM97) is aberrantly up-regulated in many human
      carcinoma cells. However, the function of MAC30 in gastric carcinoma cells is not
      studied. MATERIAL AND METHODS: To investigate the function of MAC30 in gastric
      carcinoma, we used RNA silencing technology to knock down the expression of MAC30
      in gastric cancer cells BGC-823 and AGS. Real-time quantitative PCR and Western
      blot were used to analyze the mRNA level and the related protein expression. The
      localization of MAC30 and lamellipodia was observed by immunofluorescence. The
      biological phenotypes of gastric cells were examined by cell proliferation assay,
      cell cycle analysis, apoptosis assay, cell migration and invasion assay. RESULTS:
      We found that down-regulation of MAC30 expression efficiently inhibited the
      proliferation of gastric cancer cells. Furthermore, the mobility of gastric
      cancer cells was also inhibited by down-regulation of MAC30. Moreover, we found
      that MAC30 knockdown inhibited AKT phosphorylation and reduced the expression of
      cyclinB1 and WAVE2. CONCLUSION: To our knowledge, this is the first report
      investigating the effect of MAC30 on growth, cell cycle, migration, and invasion
      in gastric carcinoma cells via suppressing AKT signaling pathway. MAC30 may be a
      potential therapeutic target for treatment of gastric carcinoma.

PMID- 24853234
TI  - Stem cell responses to nanotopography.
AB  - Cells interact with various nanoscaled topographical and biochemical cues in
      their cellular macromolecular environment. Nanotopography recreates or mimic the
      cellular macromolecular environment in vitro. The influence of material surface
      topography on the behavior of adherent cells has been studied. Current techniques
      enable various kinds of nanopatterned surface to be generated and applied to
      cells. The purpose of this review is to provide an overview of nanotopography and
      its surface patterns, and introduce nanotopography effects on cell behavior
      including cell attachment, proliferation, and cell differentiation with
      particular emphasis on musculoskeletal regeneration.

PMID- 24853235
TI  - Impact of the Great East Japan Earthquake on acute myocardial infarction in
      Fukushima prefecture.
AB  - OBJECTIVE: The incidence of cardiovascular disease (CVD) reportedly increases
      following a huge disaster. On March 11, 2011, the Great East Japan Earthquake hit
      a large area of eastern Japan. In Fukushima prefecture, many people suffered from
      the consequences of the earthquake, the subsequent tsunami, and especially the
      Fukushima Daiichi Nuclear Power Plant accident. We assessed whether the incidence
      of acute myocardial infarction (AMI) increased after the earthquake. METHODS: We
      enrolled AMI patients admitted to 36 hospitals in Fukushima prefecture between
      March 11, 2009, and March 10, 2013 (n = 3068). We compared the incidence of AMI
      after the earthquake for more than 3 months and 1 year with that in the control
      years. RESULTS: The incidence of Fukushima's annual AMI patients (per 100 000
      persons) in 2011 was similar to that of previous years (n = 38.9 [2011] vs 37.2
      [2009] and 38.5 [2010], P = .581). However, a significantly higher incidence of
      AMI was found in the Iwaki district after the disaster that corresponded to the 1
      year period of observation (n = 38.7 [2011] vs 27.3 [2009] and 32.8 [2010], P =
      .045). CONCLUSION: The Great East Japan Earthquake affected the incidence of AMI
      only in limited areas of Fukushima prefecture.

PMID- 24853236
TI  - Interface controls spontaneous crystallization in thin films of the ionic liquid
      [C2C1Im][OTf] on atomically clean Pd(111).
AB  - A total of 5-30 monolayer thick films of the ionic liquid (IL) [C2C1Im][OTf] were
      vaporized in vacuo onto an atomically clean Pd(111) single crystal surface at 220
      K. Time- and temperature-resolved infrared reflection-absorption spectroscopy
      reveals growth, interactions with the metallic support, and the macroscopic phase
      behavior of the layer. At 220 K, the IL layer first grows in the form of a glassy
      phase. Crystallization of the IL was witnessed above a critical thickness of
      about 10 monolayers. On the basis of the known bulk crystal structure of the IL,
      we suggest the formation of well-oriented checkerboard-like crystalline film
      structures on the surface. The preferential orientation manifested by the crystal
      phase with regard to the macroscopic metallic surface is attributed to strong
      interactions between anionic headgroups and the metal. 

PMID- 24853238
TI  - Examining postconcussion symptoms of dizziness and imbalance on neurocognitive
      performance in collegiate football players.
AB  - OBJECTIVE: This study examined the effects of symptom reports of dizziness and
      imbalance on cognitive function in concussed collegiate football players. DESIGN:
      Retrospective, descriptive. SETTING: University athletic medicine facility.
      SUBJECTS: Twenty-seven collegiate football players were included in the final
      analysis: 16 with symptoms of dizziness/imbalance resulting from concussion and
      11 without dizziness/imbalance resulting from concussion. MAIN OUTCOME MEASURES:
      Participants completed the Immediate Postconcussion Assessment and Cognitive
      Testing (ImPACT) at baseline, at 1 to 2 days postconcussion and 5 to 7 days
      postconcussion. The ImPACT neurocognitive assessment consists of 6 modules,
      yielding 4 composite scores: verbal memory, visual memory, visual-motor
      processing speed, and reaction time. In addition, it includes a postconcussion
      symptom scale total score. RESULTS: Results revealed that participants with
      reports of dizziness and imbalance had significantly lower scores on the ImPACT
      composite scores; however, these individuals also had an overall higher symptom
      inventory. When accounting for the additional postconcussion symptoms, time was
      the only significant effect. CONCLUSION: Dizziness and imbalance are common
      symptoms postconcussion; however, these symptoms did not predict performance on
      acute ImPACT scores. Further research is needed to understand the mechanisms
      causing postconcussion symptoms, including symptoms of dizziness and imbalance,
      and influence on outcomes postconcussion.

PMID- 24853239
TI  - Why do treatment failure and recurrences of benign paroxysmal positional vertigo
      occur?
AB  - OBJECTIVE: To investigate the potential risk factors associated to the treatment
      failure and recurrence of benign paroxysmal positional vertigo (BPPV). STUDY
      DESIGN: Prospective cohort study. SETTING: Tertiary referral center. PATIENTS:
      Four hundred patients with benign paroxysmal positional vertigo, 119 men and 281
      women, aged 27 to 88 years. INTERVENTION: Patients were treated once a week, with
      only one, appropriate, depending on the affected canal, repositioning maneuver
      (modified Epley, Semont, barbecue/inverted Gufoni, Kim). The control Dix-Hallpike
      test and the roll test were performed on 7 days. MAIN OUTCOME MEASURES: The
      treatment outcome and recurrence were evaluated with regard to sex, age, duration
      of symptoms, etiologic factors, migraines, osteoporosis, vascular risk factors,
      endocrine diseases, localization of otoconia, and simultaneous involvement of
      multiple canals. RESULTS: The results indicate that treatment was negatively
      affected by patients' age, osteoporosis, and head trauma, without them causing
      recurrent symptoms. The highest number of uncured patients was observed in the 73
      to 88-year-old age group (14.8%). The application of more than one maneuver was
      necessary in 27.5% of cases with primary BPPV and 88.9% with secondary BPPV. The
      highest treatment success was achieved in the group with BPPV of the posterior
      semicircular canal (F = 3.668, p = 0.026). The recurrence rate was 15.5%.
      CONCLUSION: Potential risk factors associated to the treatment failure were as
      follows: the age older than 50, secondary BPPV, head trauma, the occurrence of
      osteoporosis, and localization of otoconia in the anterior semicircular canal.
      The analyzed factors did not have impact on the recurrence.

PMID- 24853237
TI  - Obesity and economic environments.
AB  - This review summarizes current understanding of economic factors during the
      obesity epidemic and dispels some widely held, but incorrect, beliefs. Rising
      obesity rates coincided with increases in leisure time (rather than increased
      work hours), increased fruit and vegetable availability (rather than a decline in
      healthier foods), and increased exercise uptake. As a share of disposable income,
      Americans now have the cheapest food available in history, which fueled the
      obesity epidemic. Weight gain was surprisingly similar across sociodemographic
      groups or geographic areas, rather than specific to some groups (at every point
      in time; however, there are clear disparities). It suggests that if one wants to
      understand the role of the environment in the obesity epidemic, one needs to
      understand changes over time affecting all groups, not differences between
      subgroups at a given time. Although economic and technological changes in the
      environment drove the obesity epidemic, the evidence for effective economic
      policies to prevent obesity remains limited. Taxes on foods with low nutritional
      value could nudge behavior toward healthier diets, as could subsidies/discounts
      for healthier foods. However, even a large price change for healthy foods could
      close only part of the gap between dietary guidelines and actual food
      consumption. Political support has been lacking for even moderate price
      interventions in the United States and this may continue until the role of
      environmental factors is accepted more widely. As opinion leaders, clinicians
      play an important role in shaping the understanding of the causes of obesity.

PMID- 24853240
TI  - A soft-surgery approach to minimize hearing damage caused by the insertion of a
      cochlear implant electrode: a guinea pig animal model.
AB  - OBJECTIVE: A "soft surgery" technique was applied, using various types of
      specifically designed dummy electrodes, to mimic cochlear implantation in a
      guinea pig model, and the degree of hearing-preservation/cochlear damage was
      assessed. METHODS: Tricolor guinea pigs were divided into 3 groups: group A were
      implanted with electrodes without any contacts or wires (soft electrode), group B
      were implanted with electrodes having a metallic wire inside (stiff electrode),
      and group C underwent a cochleostomy procedure without implantation. Compound
      action potentials, in the range of 4 to 32 kHz, were used to assess
      electrophysiologic changes in the hearing function presurgery and postsurgery.
      Data were collected before surgery, at times t = 0 (immediately after surgery)
      and at 3, 7, 14, and 30 days. RESULTS: At low frequencies (4-8 kHz), an immediate
      elevation of hearing threshold was observed in all 3 groups. Higher threshold
      shifts were more consistent for group B implanted with a stiff electrode, in
      comparison to the other 2 groups. Animals from group C presented a recovery from
      hearing loss, starting 3 days after surgery. At high frequencies (16-32 kHz), the
      elevation of hearing threshold was higher, as compared with the data from the low
      frequencies. Group C animals presented oscillatory threshold shifts twice, and
      the recovery to normal threshold values occurred approximately at t = 14 days.
      CONCLUSION: The data suggest that cochleostomy is minimally harmful to the inner
      ear and that a soft electrode might better preserve the inner ear integrity than
      a rigid electrode.

PMID- 24853241
TI  - Multichannel facial nerve monitoring: value in detection of mechanically elicited
      electromyographic activity and prediction of postoperative outcome.
AB  - OBJECTIVE: To determine the value of using a multichannel facial nerve (FN)
      monitoring setup in detecting mechanically elicited EMG activity during
      vestibular schwannoma (VS) surgery. STUDY DESIGN: Prospective study. SETTING:
      Tertiary referral center. PATIENTS AND METHODS: This study was conducted on 42
      patients operated for VS removal. The FN was monitored using a 5-channel setup
      with electrodes inserted in mentalis, o.oris, nasalis, o.oculi, and frontalis.
      The number of channels activated simultaneously in response to a particular event
      was recorded together with the amplitude of response on each muscle. EMG activity
      occurring simultaneously on all 5 channels was referred to as "all-channels
      activity." Postoperative FN function was assessed immediately and 1 year
      postoperatively using the House-Brackmann classification. RESULTS: The 5-channel
      setup detected a significantly higher number of mechanically elicited EMG
      activity than would have been possible using a 2-channel setup. The number and
      amplitude of EMG activity detected on the mentalis muscle was significantly
      higher compared with other muscles. Patients with higher percentage of events in
      which the mentalis fired while o.oris and o.oculi did not were more likely to
      develop a better long-term outcome. Positive correlation was found between the
      number of all-channels activity and postoperative outcome (p < 0.001).
      CONCLUSION: The use of a multichannel setup allowed earlier and efficient
      detection of mechanically elicited EMG activity. Including the mentalis muscle
      significantly increased the detection rate, which tended to reflect as
      improvement in the long-term outcome. The occurrence of all-channels activity
      should be considered a prompt warning sign.

PMID- 24853242
TI  - Cognitive delay as a risk factor for late presentation of vestibular schwannoma.
AB  - OBJECTIVE: The majority of patients with vestibular schwannoma (VS) initially
      experience audiovestibular dysfunction prompting medical evaluation. Over the
      past several years, the authors have noticed a significant disparity in clinical
      presentation among patients with preexisting cognitive impairment compared with
      the general population. The objective of the current study is to review the
      clinical presentation of 5 consecutive patients with baseline cognitive delay who
      were ultimately diagnosed with VS. DESIGN: Retrospective review. SETTING: Two
      tertiary academic referral centers. PATIENTS: Consecutive subjects with baseline
      cognitive impairment who were evaluated for VS between 2010 and 2013. MAIN
      OUTCOME MEASURES: Presenting symptoms and tumor characteristics. RESULTS: Five
      adult subjects were identified. The most common reasons for seeking medical care
      included worsening ataxia and headaches, despite the fact that all patients had
      profound ipsilateral hearing loss. Additionally, 2 patients endorsed facial
      numbness, and 2 had partial facial paresis. MRI revealed a median preoperative
      tumor size of 4.7 cm (4.3-5.7 cm), and all patients had varying degrees of
      hydrocephalus and peritumoral vasogenic edema. CONCLUSION: Preexisting cognitive
      impairment is a risk factor for late presentation of VS. Patients with normal
      cognitive function most commonly seek medical care after unilateral hearing loss
      and tinnitus. In contrast, individuals with poor cognitive capacity may be unable
      to acknowledge such symptoms or communicate their presence. In such patients, the
      diagnosis of VS is elusive, and clinicians should maintain a low threshold for
      imaging to avoid further delays in diagnosis and treatment.

PMID- 24853243
TI  - Stability testing after osseointegrated implant surgery without skin thinning in
      children: case reports after abutment loss.
AB  - OBJECTIVE: To evaluate 2 cases of implant loss after osseointegration using low
      resonance frequency analysis. PATIENTS: Ten children were operated on
      consecutively with the non-skin-thinning implantation of bone-anchored hearing
      devices. A capsule report was completed with 2 children who experienced loss of
      their abutments 3 to 4 weeks after implantation. INTERVENTION: Eligible children
      for bone-anchored hearing device implantation were operated on and followed for a
      total of 1 year. Visits were planned for 1 week, 3 months, 6 months, and 12
      months after surgery. Each visit included clinical controls and a stability test
      with Osstell's resonance frequency analysis measurement, using stability values
      from 0 to 100 (representing a range of low to high stability, respectively). Of
      the 10 cases, two were performed as a 2-step, whereas the other 8 were performed
      as a 1-step non-skin-thinning procedure. MAIN OUTCOME MEASURE AND RESULTS: Two of
      the children (1 two-step and 1 one-step) showed low-resonance measurements of 30
      or less after surgery. Both of these children lost their abutments early after
      surgery. These children had no skin-related problems at the time of abutment
      loss. CONCLUSION: It may be possible to predict abutment loss in children with
      primary resonance values lower than 30.

PMID- 24853244
TI  - Long-term follow-up results of canal wall down tympanoplasty with mastoid
      obliteration using the bone pate plate for canal wall reconstruction in
      cholesteatoma surgery.
AB  - BACKGROUND: The pathogenesis of recurrent cholesteatoma can be roughly divided
      into residual lesions and re-retraction of the epithelium. To prevent both
      residual and re-retraction cholesteatoma, we performed canal wall down
      tympanoplasty with mastoid obliteration using the bone pate plate for canal wall
      reconstruction as a fundamental surgical treatment for patients with acquired
      cholesteatoma. We attempted to achieve the complete extirpation of cholesteatoma
      in the wide surgical field made by the canal wall down procedure and
      simultaneously prevent recurrent retraction cholesteatoma and regain the
      physiologic canal wall, in which patients can have a "maintenance-free ear."
      OBJECTIVE: The surgical method used in the present study was described, and the
      long-term postoperative results of this method were evaluated. STUDY DESIGN:
      Retrospective study. PATIENTS: Participants were 118 patients with acquired
      cholesteatoma who underwent canal wall down tympanoplasty with mastoid
      obliteration and could be followed-up for more than 5 years. MAIN OUTCOME
      MEASURES: Postoperative changes in the reconstructed canal wall, the rate of
      otorrhea, and exposure of the material were examined using endoscopic images,
      medical charts, and CT scans. RESULTS: A total of 113 ears (95.8 %) achieved the
      nearly physiologic appearance of the external auditory canal, and these
      conditions were maintained throughout the follow-up periods. However, recurrent
      cholesteatoma was not observed during the follow-up periods. Postoperative
      otorrhea was observed in 2.5% of ears. Exposure of the bone pate was only noted
      in 1 patient (0.8 %). Postoperative CT scans confirmed that ossification
      developed in the bone pate used in the reconstructed canal wall and mastoid
      surface. CONCLUSION: Canal wall down tympanoplasty with mastoid obliteration
      using the bone pate plate for canal wall reconstruction prevents both recurrent
      and residual cholesteatoma and contributes to a good quality of life for the
      patient.

PMID- 24853245
TI  - The shape of the osseous external auditory canal and its relationship to chronic
      external otitis.
AB  - BACKGROUND: In literature and based on clinical observations, the shape of the
      osseous external auditory canal (OEAC) has often been suggested to be an
      etiologic factor in chronic otitis externa (COE). However, to date, no evidence
      has been presented to confirm this correlation. The aim of this study was to see
      whether evidence of such a correlation exists, and if so, what shape of the OEAC
      is related to COE. METHODS: Using CT scans of 2 groups of patients (with and
      without COE), a novel and easy to use method was introduced to measure 2
      dimensions of the OEAC: the pretympanic recess (the depth (DPTR) and anterior
      curvature (ACPTR)). In addition, a descriptive classification of the entire OAEC
      was introduced. RESULTS: The proposed method was demonstrated to be useful as
      excellent interobserver agreements were found (r = 0.89). No significant
      differences in the descriptive classifications of the OEAC were observed between
      COE and the non-COE patients. The DPTR was significantly deeper in COE patients.
      For the ACPTR, no significant differences were observed. CONCLUSION: Based on a
      new method of determining the DPTR, we demonstrate that the DPTR is significantly
      deeper in COE patients and that the shape of the OEAC is thus of importance in
      the pathogenesis of COE.

PMID- 24853246
TI  - Facial nerve schwannomas presenting as occluding external auditory canal masses:
      a therapeutic dilemma.
AB  - OBJECTIVE: To present a series of patients with facial nerve schwannomas (FNSs)
      presenting as occluding external auditory canal (EAC) masses. STUDY DESIGN:
      Retrospective case series. PATIENTS: Four patients were identified with mastoid
      segment FNSs occluding the EAC. Three patients presented with conductive hearing
      loss (CHL), and the fourth presented with facial paralysis, later developing CHL.
      INTERVENTION: One patient underwent conservative debulking, removing the EAC
      component only. Two patients were managed nonoperatively with periodic cleaning
      of entrapped keratin. The fourth patient received radiation therapy. MAIN OUTCOME
      MEASURES: Facial nerve function, canal cholesteatoma formation, and hearing.
      RESULTS: Among the patients managed with serial cleaning of entrapped keratin,
      one maintained normal facial function and one worsened to House-Brackmann II/VI.
      Facial function worsened to House-Brackmann II/VI in the patient who underwent
      surgical debulking. The fourth patient, who received radiation, developed
      complete facial paralysis. All patients accumulated keratin medial to the tumor,
      and all had CHL. CONCLUSION: When evaluating an EAC tumor, it is important to
      obtain imaging before biopsy because biopsy of a schwannoma can result in
      paralysis. EAC occlusion by a schwannoma presents a challenging management issue,
      particularly when cholesteatoma forms between the tumor and the tympanic
      membrane. The primary goal is maintaining normal facial function as long as
      possible and avoiding secondary ear canal complications. The presence of canal
      occlusion limits the choice of stereotactic radiation because this leads to a
      month-long period of tumor swelling and cutaneous sloughing. Resection and
      grafting are indicated when substantial facial weakness or twitch develops.

PMID- 24853247
TI  - Acute and subacute chemical-induced lung injuries: HRCT findings.
AB  - Lung injury caused by chemicals includes bronchitis, bronchiolitis, chemical
      pneumonitis, pulmonary edema, acute respiratory distress syndrome, organizing
      pneumonia, hypersensitivity pneumonitis, acute eosinophilic pneumonia, and
      sarcoid-like granulomatous lung disease. Each chemical induces variable
      pathophysiology and the situation resembles to the drug induced lung disease. The
      HRCT features are variable and nonspecific, however HRCT may be useful in the
      evaluation of the lung injuries and so we should know about HRCT features of lung
      parenchymal abnormalities caused by chemicals.

PMID- 24853248
TI  - Room-temperature ligand-free Pd/C-catalyzed C-S bond formation: synthesis of 2
      substituted benzothiazoles.
AB  - The synthesis of 2-substituted benzothiazoles has been achieved via cyclization
      of o-iodothiobenzanilide derivatives using Pd/C as the catalyst at room
      temperature. The protocol is ligand-free, additive-free, and high-yielding and
      involves very mild conditions. 

PMID- 24853249
TI  - The cognitive cost of event-based prospective memory in children.
AB  - Prospective memory is the act of remembering to perform an action in the future,
      often after the presentation of a cue. However, processes involved in remembering
      the future intention might hinder performance on activities leading up to and
      surrounding the event in which an intention must be carried out. The current
      study was designed to assess whether young children who were asked to engage in
      prospective memory do so at a cost to current cognitive processing. Participants
      (4-, 5-, and 6-year-olds) either performed a simple ongoing selection task only
      (control condition) or performed the selection task with an embedded prospective
      memory task (experimental condition). Results revealed that children in the
      experimental condition were slower in the execution of the ongoing task relative
      to children in the control condition, lending support to the theory that children
      as young as 4 ears selectively allocate resources in an effort to succeed in
      multiple tasks.

PMID- 24853250
TI  - Association between physical activity and mortality in breast cancer: a meta
      analysis of cohort studies.
AB  - Previous studies concerning the association between physical activity (PA) and
      mortality in breast cancer yielded mixed results. We investigated the association
      by performing a meta-analysis of all available studies. Relevant studies were
      identified by searching PubMed and EMBASE to January 2014. We calculated the
      summary relative risk (RR) and 95 % confidence intervals (CIs) using random
      effects models. The dose-response relationship was assessed by restricted cubic
      spline model and multivariate random-effect meta-regression. Sixteen cohort
      studies involving 42,602 patients of breast cancer were selected for meta
      analysis. The analyses showed that patients who participated in any amount of PA
      before diagnosis had a RR of 0.82 (95 % CI 0.74-0.91) for breast cancer-specific
      mortality (vs. low PA). Those who participated in high PA and moderate PA before
      diagnosis had a RR of breast cancer-specific mortality of 0.81 (95 % CI 0.72
      0.90) and 0.83 (95 % CI 0.73-0.94), respectively. Similar inverse associations of
      prediagnosis PA were found for all-cause mortality. Postdiagnosis PA on breast
      cancer-specific and all-cause mortality also showed the same results. Stratifying
      by body mass index (<25 vs. >=25) or menopausal status, all the subgroups
      experienced benefits with PA, with a stronger mortality reduction among
      overweight women than normal weight women and among postmenopausal women than
      premenopausal women. A linear and significant dose-response association was only
      found for breast cancer-specific or all-cause mortality and prediagnosis PA (P
      for nonlinearity = 0.07 and 0.10, respectively). In conclusion, both prediagnosis
      and postdiagnosis PA were associated with reduced breast cancer-specific
      mortality and all-cause mortality.

PMID- 24853251
TI  - Induction or exacerbation of psoriasis in patients with Crohn's disease under
      treatment with anti-TNF antibodies.
AB  - BACKGROUND AND AIMS: Paradoxically, psoriasis or psoriasiform skin lesions
      induced or exacerbated by anti-TNF antibodies have been described. Here, we
      report a series of 13 novel cases featuring exacerbation or occurrence of
      psoriatic skin lesions induced by anti-TNF antibodies in patients with Crohn's
      disease (CD). METHODS: We performed a systematic analysis of exacerbation or
      occurrence of psoriasis or psoriasiform skin lesions induced by anti-TNF
      antibodies in an inflammatory bowel disease patient cohort at the University
      Hospital Zurich. RESULTS: We identified 13 CD patients who developed psoriasis or
      psoriasiform lesions while receiving anti-TNF therapy. 10 of the 13 patients were
      female with an average age of 26.9 years at diagnosis. 11 of the 13 patients had
      a complicated disease. The mean time of clinical latency between diagnosis and
      onset of psoriasis was about 9.4 years, and the time between the beginning of all
      biological infusions and the onset of psoriasis was about 7 months. 7 of the 13
      patients received infliximab, 3 adalimumab, and 3 certolizumab pegol at onset of
      psoriasis. In most of the cases, anti-TNF therapy was changed or discontinued and
      skin lesions improved. CONCLUSION: Most of our described patients featured a
      complicated disease course of CD and had an improvement of the rash after
      changing the anti-TNF therapy.

PMID- 24853252
TI  - Manipulating and probing enzymatic conformational fluctuations and enzyme
      substrate interactions by single-molecule FRET-magnetic tweezers microscopy.
AB  - Enzyme-substrate interaction plays a critical role in enzymatic reactions,
      forming the active enzyme-substrate complex, the transition state ready to react.
      Studying the enzyme-substrate interaction will help in the ultimate molecular
      level characterization of the enzymatic transition state that defines the
      reaction pathway, energetics, and the dynamics. In our initial effort to
      experimentally investigate the enzyme-substrate interactions and the related
      conformational fluctuations, we have developed a new approach to manipulate the
      enzymatic conformation and enzyme-substrate interaction at a single-molecule
      level by using a combined magnetic tweezers and simultaneous fluorescence
      resonance energy transfer (FRET) spectroscopic microscopy. By a repetitive
      pulling-releasing manipulation of a Cy3-Cy5 dye labeled 6-hydroxymethyl-7,8
      dihydropterin pyrophosphokinase (HPPK) molecule under the conditions with and
      without enzymatic substrates, we have probed and analyzed the enzymatic
      conformational dynamics. Our results indicate that the enzyme conformational
      flexibility can be regulated by enzyme-substrate interactions: (1) enzyme at its
      conformation-perturbed state has less flexibility when binding substrates, and
      (2) substrate binding to enzyme significantly changes the enzyme conformational
      flexibility, an experimental evidence of so called entropy trapping in the enzyme
      substrate reactive transition state. Furthermore, our results provide a
      significant experimental analysis of the folding-binding enzyme-substrate
      interactions, a dynamic nature of the enzymatic active transition state formation
      process. 

PMID- 24853253
TI  - Intraoperative neurophysiological monitoring in pediatric neurosurgery.
AB  - The use of intraoperative neurophysiological monitoring (IONM) in pediatric
      neurosurgery is not new; however, its application to a wider range of procedures
      is a relatively new development. The purpose of this article is to review the
      physiology underlying the commonly employed IONM modalities and to describe their
      application to a subset of pediatric neurosurgical procedures. 

PMID- 24853254
TI  - Acquired thrombotic thrombocytopenic purpura due to antibody-mediated ADAMTS13
      deficiency precipitated by a localized Castleman's disease: a case report.
AB  - Acquired ADAMTS13 inhibitor causing thrombotic thrombocytopenic purpura (TTP) may
      be precipitated by some infections, inflammatory diseases or neoplasia. We
      reported a case of refractory TTP precipitated by a newly diagnosed localized
      Castleman's disease (CD). TTP was initially treated with plasma exchange and
      immunosuppressive therapy with corticosteroids; however the treatment failed to
      promote sustained response. During hospitalization, an abdominal tumor was
      diagnosed and resected; the histological analysis revealed a CD of hyaline
      vascular variant rich stroma. After tumor removal, the patient achieved a long
      lasting clinical remission and normalized ADAMTS13 activity. This clinical case
      describes a novel association of acquired ADAMTS13 inhibitor and CD. The antibody
      to ADAMTS13 developed along with the systemic manifestation of CD and promptly
      disappeared after the resection of the tumor. There are reports of neoplasia
      associated thrombotic microangiopathy however direct evidence of CD-dependent
      ADAMTS13 inhibitor had not yet been reported. 

PMID- 24853256
TI  - A clinical test of lumbopelvic control: development and reliability of a clinical
      test of dissociation of lumbopelvic and thoracolumbar motion.
AB  - LBP is often associated with changes in motor control. Some subgroups of LBP have
      been argued to have a compromised ability to dissociate lumbopelvic movement from
      that of the thoracolumbar junction. Clinical methods to evaluate this task may
      aid identification of this LBP subgroup and determine the utility of this
      information to guide clinical interventions. The study aimed to develop a
      clinical test to assess the ability to dissociate lumbopelvic movement from that
      of the thoracolumbar junction, and to evaluate the inter-rater reliability of the
      test in individuals with and without low back pain (LBP) when performed by
      experienced and novice therapists. A clinical scale was developed to characterise
      quality of performance of lumbopelvic motion with limited motion at the
      thoracolumbar junction. Inter-tester repeatability was measured in three
      experiments. Test outcomes for pain-free controls were compared between three
      assessors with different amounts of clinical experience. Test scores for LBP
      participants were compared between two assessors, and between assessments
      undertaken from video recordings. Agreement between assessors was tested with
      weighted Kappa Coefficient. The test had acceptable reliability in pain-free and
      LBP participants, but was better when undertaken by experienced therapists. Kappa
      index ranged from 0.81 to 0.66 for live assessments, and 0.62 for video
      assessments. The results showed that the test is reliable when performed by
      experienced assessors. The test can assess thoracolumbar movements in different
      groups of individuals. 

PMID- 24853255
TI  - Altered postural responses persist following physical therapy of general versus
      specific trunk exercises in people with low back pain.
AB  - Interventions that target trunk muscle impairments in people with LBP have been
      promoted; however, the treatment effects on muscle activation impairments during
      postural tasks remain unclear. Thus, our objective was to evaluate the effects
      trunk stabilization vs. general strength and conditioning exercises on the
      automatic postural response in persons with chronic low back pain (LBP). Fifty
      eight subjects with chronic, recurrent LBP (n = 58) (i.e., longer than six
      months) were recruited and randomly assigned to one of two, 10-week physical
      therapy programs: stabilization (n = 29) or strength and conditioning (n = 29).
      Pain and function were measured at 11 weeks and 6 months post-treatment
      initiation. To quantify postural following support surface perturbations, surface
      electrodes recorded electromyography (EMG) of trunk and leg muscles and force
      plates recorded forces under the feet, to calculate the center of pressure. Both
      groups demonstrated significant improvements in pain and function out to 6
      months. There were also changes in muscle activation patterns immediately post
      treatment, but not at 6 months. However, changes in center of pressure (COP)
      responses were treatment specific. Following treatment, the stabilization group
      demonstrated later onset of COP displacement, while the onset of COP displacement
      in the strengthening group was significantly earlier following treatment. Despite
      two different treatments, clinical improvements and muscle activation patterns
      were similar for both groups, indicating that the stabilization treatment
      protocol does not preferentially improve treatment outcomes or inter-muscle
      postural coordination patterns for persons with LBP. CLINICAL TRIAL REGISTRATION
      NUMBER: NCT01611792.

PMID- 24853258
TI  - Patient preference with respect to QoL and reduction in opioid-induced
      constipation (OIC) after treatment with prolonged-release (PR) oxycodone/naloxone
      compared with previous analgesic therapy [PREFER study].
AB  - OBJECTIVE: The aim of this study was to assess patient preference in terms of
      quality of life (QoL), analgesia and bowel function for patients with moderate to
      severe chronic non-malignant pain, when treated with oxycodone PR/naloxone PR
      compared with the previous WHO-step I and/or WHO-step II analgesic treatment .
      STUDY DESIGN: This was a 3-week open-label phase 3b study conducted in Belgium
      and the Netherlands, after 3 weeks patients could enter an extension phase.
      Patient preference with respect to QoL for oxycodone PR/naloxone PR treatment
      compared with previous WHO-step I and/or WHO-step II analgesics was assessed. A
      patient was considered a responder with respect to QoL if this assessment was
      'better' or 'much better' compared with previous WHO-step I or II analgesics at
      any time point. RESULTS: Response rate with respect to QoL was 59.2% (95% CI:
      51.7-66.8%) for the Full Analysis (FA)-population, for the Per Protocol
      population response rate was 71.7% (95% CI: 63.1-80.3%). Explorative analysis
      showed that response rate with respect to QoL was highest in constipated patients
      pretreated with WHO-step II analgesics (73.8%). Mean +/- SD pain score in the FA
      population at start was 74.7 +/- 16.6 decreasing to 53.9 +/- 24.3 after a median
      (range) treatment period of 173.5 (31-771) days. For constipated subjects the
      significant reduction in constipation [improvement of the Bowel Function Index
      (BFI)], was -24.8 points (95% CI: -17.1 to -32.5). BFI for non-constipated
      subjects remained well below 28.8. Adverse events with oxycodone PR/naloxone PR
      treatment were well-known opioid-related adverse events. CONCLUSION: This study
      shows that the studied patients previously treated with WHO-step I and/or WHO
      step II analgesics prefer treatment with oxycodone PR/naloxone PR with respect to
      QoL. Moreover, the study shows that treatment with oxycodone PR/naloxone PR
      significantly reduces OIC in constipated patients and that non-constipated
      patients do not develop OIC during treatment with oxycodone PR/naloxone PR.

PMID- 24853257
TI  - Variable ganciclovir concentrations in a critically ill patient receiving
      continuous renal replacement therapy and plasma exchange?

PMID- 24853259
TI  - Community knowledge, health beliefs, practices and experiences related to dengue
      fever and its association with IgG seropositivity.
AB  - BACKGROUND: Demographic, economic and behavioural factors are central features
      underpinning the successful management and biological control of dengue. This
      study aimed to examine these factors and their association with the
      seroprevalence of this disease. METHODOLOGY: We conducted a cross-sectional
      telephone survey of households in a 3 km radius of the schools where we had
      conducted serological tests on the student population in a previous study.
      Households were surveyed about their socio-demographics, knowledge, practices,
      and Health Belief Model (HBM) constructs. The results were then associated with
      the prevalence rate of dengue in the community, as marked by IgG seropositivity
      of the students who attended school there. RESULTS: A total of 1,400 complete
      responses were obtained. The community's IgG seropositivity was significantly
      positively associated with high household monthly income, high-rise residential
      building type, high surrounding vegetation density, rural locality, high
      perceived severity and susceptibility, perceived barriers to prevention, knowing
      that a neighbour has dengue, frequent fogging and a higher level of knowledge
      about dengue. In the multivariate analyses, three major correlates of the
      presence of IgG seropositivity in the community: (1) high-rise residential
      apartment house type or condominium buildings; (2) the main construct of the HBM,
      perceived severity and susceptibility; and (3) the additional constructs of the
      HBM, lack of preventive measures from the community level and having a neighbour
      with dengue as a cue to action. Weak correlations were found between self
      practices to prevent dengue and the level of dengue seropositivity in the
      community, and between HBM constructs and knowledge (r = 0.09). CONCLUSIONS: The
      residential environment factor and the constructs of the HBM are useful and
      important elements in developing interventions to prevent and control dengue. The
      study also sheds light on the importance of the need for approaches that ensure
      the translation of knowledge into practice.

PMID- 24853260
TI  - Specific antibodies in oral immunotherapy for cow's milk allergy: kinetics and
      prediction of clinical outcome.
AB  - BACKGROUND: METHODS for predicting the clinical outcome of specific oral
      immunotherapy (OIT) would improve the safety of the therapy. METHODS: We
      investigated 40 children aged 6-17 years with IgE-mediated cow's milk allergy
      (CMA) who either successfully completed OIT (n = 32) or discontinued the therapy
      due to adverse reactions (n = 8). From sera drawn before and after OIT, we
      analyzed specific IgA, IgG, IgG1 and IgG4 to cow's milk (CM), casein, beta
      lactoglobulin and ovalbumin (with enzyme-linked immunosorbent assay) and IgE to
      CM and hen's egg white [with enzymatic fluoroimmunoassay (Phadia ThermoFisher
      Scientific CAP system)]. As a reference, we also analyzed serum samples from 8-
      to 9-year-old children who either had no history of CMA (n = 76) or who had
      spontaneously recovered from IgE-mediated CMA (n = 56). RESULTS: Levels of
      specific IgA, IgG, IgG1 and IgG4 to CM and casein, and CM-specific IgE prior to
      OIT were higher in children who discontinued the therapy than in those who
      achieved desensitization (p < 0.05). Adverse reactions in the entire population
      were associated with low IgG and IgG4, but high IgG1 levels to ovalbumin (p <
      0.05). Specific IgA, IgG, IgG1 and IgG4 to CM proteins significantly increased
      and IgE to CM decreased during OIT in children who achieved desensitization (p <
      0.01). In those who discontinued OIT, only IgG, IgG1 and IgG4 to CM increased
      significantly (p < 0.03) and CM IgE remained unchanged. CONCLUSIONS: High
      specific IgE, IgA and IgG-class antibodies to CM proteins appear to predict
      failure to achieve desensitization in CM OIT. Specific IgA and IgG-class
      antibodies to CM increase and CM IgE decreases during desensitization.

PMID- 24853261
TI  - Apparent progression of presbyopia after laser in situ keratomileusis in patients
      with early presbyopia.
AB  - PURPOSE: To assess the effect of laser in situ keratomileusis (LASIK) on near
      visual function in presbyopic patients. DESIGN: Retrospective cohort study.
      METHODS: Fifty-three eyes of 40 patients 45 years of age and older who had
      undergone LASIK for high myopia (-6 diopters [D] and over) were included. The
      minimal add powers for obtaining the best-corrected near visual acuity (add
      powers) were measured preoperatively and 3 months postoperatively, and the
      correlations with the powers corrected by LASIK, corneal higher-order aberrations
      (HOAs), ocular HOAs, and patient ages were evaluated using univariate analysis.
      Factors correlated with the changes in add powers were evaluated further by
      multivariate analysis. RESULTS: The mean +/- standard deviation patient age was
      50.0 +/- 4.1 years; the power corrected by LASIK was -7.56 +/- 1.06 D. The mean
      add power was 1.80 +/- 0.60 D preoperatively, which increased significantly (P <
      .001) to 2.18 +/- 0.69 D postoperatively. Significant correlations with the
      increased add powers were detected with age (P = .01) and the power corrected by
      LASIK (P = .04) but not with corneal and ocular HOAs (P > .05). Multivariate
      analysis showed that only age was correlated significantly (P = .01). The
      percentage of eyes with increased add powers of 0.5 D or more was 60.4%, which
      was significantly (P = .02) higher in younger patients. CONCLUSIONS: This study
      verified the apparent progression of presbyopia after LASIK and the importance of
      obtaining informed consent from patients, especially those with early presbyopia.

PMID- 24853263
TI  - Mechanistic insights from DGT and soil solution measurements on the uptake of Ni
      and Cd by radish.
AB  - This work tests the previously proposed hypothesis that plant uptake of metals is
      determined dominantly by diffusional controlled or plant limiting uptake
      mechanisms at, respectively, low and high metal concentrations. Radish (Raphanus
      sativus) was grown in 13 soils spiked with Ni (10 and 100 mg kg(-1)) and Cd (0.5
      and 4 mg kg(-1)) for 4 weeks to investigate the mechanisms affecting plant
      uptake. Soil solution concentrations, Css, of Ni and Cd were measured, along with
      the DGT interfacial concentration, CDGT, and the derived effective concentration
      in soil solution, CE. Free ion activities, aNi(2+) and aCd(2+), were obtained
      using WHAM 6. Although there was a poor relationship between Ni in radish roots
      and either Css or aNi(2+) in unamended soils, the distribution of data could be
      rationalized in terms of the extent of release of Ni from the soil solid phase,
      as identified by DGT and soil solution measurements. By contrast Ni in radish was
      linearly related to CE, demonstrating diffusion limited uptake. For soils amended
      with high concentrations of Ni, linear relationships were obtained for Ni in
      radish plotted against, Css, aNi(2+), and CE, consistent with the plant
      controlling uptake. For Ni the hypothesis concerning dominant diffusional and
      plant limiting uptake mechanisms was demonstrated. Poor relationships between Cd
      in radish and Css, aCd(2+), and CE, irrespective of amendment by Cd, showed the
      importance of factors other than diffusional supply, such as rhizosphere and
      inhibitory processes, and that fulfilment of this hypothesis is plant and metal
      specific. 

PMID- 24853262
TI  - EndoGlide versus EndoSerter for the insertion of donor graft in descemet
      stripping automated endothelial keratoplasty.
AB  - PURPOSE: To compare 2 lenticule insertion methods currently in use for Descemet
      stripping automated endothelial keratoplasty (DSAEK). DESIGN: Prospective
      randomized single-masked study. PATIENTS AND METHODS: Twenty patients with Fuchs
      endothelial dystrophy and pseudophakic bullous keratopathy undergoing DSAEK
      surgery were included and randomized to the use of either EndoGlide or EndoSerter
      as a delivery method for the donor lenticule. Post surgery, patients were
      monitored for up to 1 year. Evaluation included corrected distance visual acuity
      (CDVA) and refraction. Specular microscopy images were obtained at the 6- and 12
      month visits. Complications, including rebubbling rate, graft dislocation, and
      graft failure, were recorded. RESULTS: Twenty eyes were randomized to receive the
      Tan EndoGlide or the EndoSerter injector for lenticule insertion. Mean patient
      age was 65.9+/-8.4 years and 70.3+/-9.8 years in the Tan EndoGlide and EndoSerter
      groups, respectively (P=.3). Two eyes in each group needed rebubbling. The mean
      endothelial cell loss, including the rebubbled eyes, at the 12-month visit was
      1093+/-629 cells/mm2 (range: 239-2109 cells/mm2, mean percentage cell loss 41.2%)
      and 877+/-566 cells/mm2 (range: 116-1851 cells/mm2, mean percentage cell loss
      31.4%) in the Tan EndoGlide and EndoSerter groups, respectively (P=.45). Mean
      CDVA did not show a statistically significant difference between the 2 groups at
      the 6- or 12-month visit. CONCLUSION: The EndoSerter shows comparable results to
      the Tan EndoGlide. However, further investigation is warranted in order to
      validate these findings.

PMID- 24853264
TI  - 2014 ISCB Accomplishment by a Senior Scientist Award: Gene Myers.

PMID- 24853265
TI  - The effect of epigallocatechin gallate on hepatocytes isolated from normal and
      partially hepatectomized rats.
AB  - Epigallocatechin gallate (EGCG) is an antioxidant found in green tea. In this
      study, male Wistar rats were subjected either to partial hepatectomy (PHx), or a
      sham operation (LAP). Twenty-four hours after surgery, hepatocytes were isolated
      and treated with various concentrations of EGCG for up to 72 h. We then measured
      markers of cell viability, oxidative stress, DNA synthesis, and caspase activity.
      Morphological criteria, cell viability tests, and albumin synthesis revealed
      toxicity starting at 10 MUmol/L. DNA synthesis was higher in hepatocytes isolated
      from rats after PHx and inhibited by EGCG. Furthermore, EGCG increased the
      activity of caspases 3 and 7, seen more in hepatocytes from PHx rats. In
      conclusion, EGCG at a concentration of 10 MUmol/L was toxic for hepatocytes
      isolated from both PHx and LAP rats. 

PMID- 24853266
TI  - A coding method for efficient subgraph querying on vertex- and edge-labeled
      graphs.
AB  - Labeled graphs are widely used to model complex data in many domains, so subgraph
      querying has been attracting more and more attention from researchers around the
      world. Unfortunately, subgraph querying is very time consuming since it involves
      subgraph isomorphism testing that is known to be an NP-complete problem. In this
      paper, we propose a novel coding method for subgraph querying that is based on
      Laplacian spectrum and the number of walks. Our method follows the filtering-and
      verification framework and works well on graph databases with frequent updates.
      We also propose novel two-step filtering conditions that can filter out most
      false positives and prove that the two-step filtering conditions satisfy the no
      false-negative requirement (no dismissal in answers). Extensive experiments on
      both real and synthetic graphs show that, compared with six existing counterpart
      methods, our method can effectively improve the efficiency of subgraph querying. 

PMID- 24853267
TI  - Knockout of endothelial cell-derived endothelin-1 attenuates skin fibrosis but
      accelerates cutaneous wound healing.
AB  - Endothelin (ET)-1 is known for the most potent vasoconstrictive peptide that is
      released mainly from endothelial cells. Several studies have reported ET-1
      signaling is involved in the process of wound healing or fibrosis as well as
      vasodilation. However, little is known about the role of ET-1 in these processes.
      To clarify its mechanism, we compared skin fibrogenesis and wound repair between
      vascular endothelial cell-specific ET-1 knockout mice and their wild-type
      littermates. Bleomycin-injected fibrotic skin of the knockout mice showed
      significantly decreased skin thickness and collagen content compared to that of
      wild-type mice, indicating that bleomycin-induced skin fibrosis is attenuated in
      the knockout mice. The mRNA levels of transforming growth factor (TGF)-beta were
      decreased in the bleomycin-treated skin of ET-1 knockout mice. On the other hand,
      skin wound healing was accelerated in ET-1 knockout mice, which was indicated by
      earlier granulation tissue reduction and re-epithelialization in these mice. The
      mRNA levels of TGF-beta, tumor necrosis factor (TNF)-alpha and connective tissue
      growth factor (CTGF) were reduced in the wound of ET-1 knockout mice. In
      endothelial ET-1 knockout mouse, the expression of TNF-alpha, CTGF and TGF-beta
      was down-regulated. Bosentan, an antagonist of dual ET receptors, is known to
      attenuate skin fibrosis and accelerate wound healing in systemic sclerosis, and
      such contradictory effect may be mediated by above molecules. The endothelial
      cell-derived ET-1 is the potent therapeutic target in fibrosis or wound healing,
      and investigations of the overall regulatory mechanisms of these pathological
      conditions by ET-1 may lead to a new therapeutic approach. 

PMID- 24853268
TI  - Affecting speed and accuracy in perception.
AB  - An account of affective modulations in perceptual speed and accuracy (ASAP:
      Affecting Speed and Accuracy in Perception) is proposed and tested. This account
      assumes an emotion-induced inhibitory interaction between parallel channels in
      the visual system that modulates the onset latencies and response durations of
      visual signals. By trading off speed and accuracy between channels, this
      mechanism achieves (a) fast visuo-motor responding to course-grained information,
      and (b) accurate visuo-attentional selection of fine-grained information. ASAP
      gives a functional account of previously counterintuitive findings, and may be
      useful for explaining affective influences in both featural-level single-stimulus
      tasks and object-level multistimulus tasks. 

PMID- 24853270
TI  - Non-invasive wearable electrochemical sensors: a review.
AB  - Wearable sensors have garnered considerable recent interest owing to their
      tremendous promise for a plethora of applications. Yet the absence of reliable
      non-invasive chemical sensors has greatly hindered progress in the area of on
      body sensing. Electrochemical sensors offer considerable promise as wearable
      chemical sensors that are suitable for diverse applications owing to their high
      performance, inherent miniaturization, and low cost. A wide range of wearable
      electrochemical sensors and biosensors has been developed for real-time non
      invasive monitoring of electrolytes and metabolites in sweat, tears, or saliva as
      indicators of a wearer's health status. With continued innovation and attention
      to key challenges, such non-invasive electrochemical sensors and biosensors are
      expected to open up new exciting avenues in the field of wearable wireless
      sensing devices and body-sensor networks, and thus find considerable use in a
      wide range of personal health-care monitoring applications, as well as in sport
      and military applications.

PMID- 24853269
TI  - Adult age differences in frontostriatal representation of prediction error but
      not reward outcome.
AB  - Emerging evidence from decision neuroscience suggests that although younger and
      older adults show similar frontostriatal representations of reward magnitude,
      older adults often show deficits in feedback-driven reinforcement learning. In
      the present study, healthy adults completed reward-based tasks that did or did
      not depend on probabilistic learning, while undergoing functional neuroimaging.
      We observed reductions in the frontostriatal representation of prediction errors
      during probabilistic learning in older adults. In contrast, we found evidence for
      stability across adulthood in the representation of reward outcome in a task that
      did not require learning. Together, the results identify changes across adulthood
      in the dynamic coding of relational representations of feedback, in spite of
      preserved reward sensitivity in old age. Overall, the results suggest that the
      neural representation of prediction error, but not reward outcome, is reduced in
      old age. These findings reveal a potential dissociation between cognition and
      motivation with age and identify a potential mechanism for explaining changes in
      learning-dependent decision making in old adulthood. 

PMID- 24853272
TI  - A nucleation-based method to study hydrophobic interactions under confinement:
      enhanced hydrophobic association driven by energetic contributions.
AB  - A novel simulation approach was developed and applied to the study of hydrophobic
      interactions for a small hydrophobic solute pair under confinement. In this
      method, the aggregation-volume-bias Monte Carlo algorithm, developed originally
      for nucleation studies, is used to evaluate the association free energy with
      water molecules for a methane pair through the gradual addition of water
      molecules into a nanometer-sized sphere. Through a thermodynamic cycle, this
      method allows for a convenient examination of the free energy difference between
      two different solvated configurations without sampling any of the configurations
      in between. The potential of mean force (PMF) for a methane pair under
      confinement obtained from this method reveals that the stability of the contact
      pair configuration can be enhanced compared to that in bulk water, which is in
      agreement with previous studies. Also, constraining the center of this methane
      pair at the center of this confined volume yields a PMF with a metastable solvent
      separated configuration, resembling more closely the PMF from the bulk-phase
      system compared to previous studies in which this solvent-separated minimum was
      found to be completely absent. A combination with histogram reweighting enables
      the study of this association behavior at different thermodynamic conditions
      without additional simulations. From a comprehensive thermodynamic analysis, it
      is evident that such hydrophobic association, known to be entropically driven in
      the bulk-phase system at ambient conditions, is entropically favorable only when
      a suitable range of solvent molecules is added to the confined system. More
      importantly, the energetic contributions are a favorable factor that explains the
      enhanced hydrophobic association toward the high number of solvent molecules. 

PMID- 24853271
TI  - Rapid reconstitution of functionally active 6-sulfoLacNAc(+) dendritic cells
      (slanDCs) of donor origin following allogeneic haematopoietic stem cell
      transplant.
AB  - The role of dendritic cells (DCs) and macrophages in allogeneic haematopoietic
      stem cell transplant (HSCT) is critical in determining the extent of graft-versus
      host response. The goal of this study was to analyse slanDCs, a subset of human
      proinflammatory DCs, in haematopoietic stem cell (HSC) sources, as well as to
      evaluate their 1-year kinetics of reconstitution, origin and functional
      capacities in peripheral blood (PB) and bone marrow (BM) of patients who have
      undergone HSCT, and their presence in graft-versus-host disease (GVHD) tissue
      specimens. slanDCs were also compared to myeloid (m)DCs, plasmacytoid (p)DCs and
      monocytes in HSC sources and in patients' PB and BM throughout reconstitution.
      slanDCs accounted for all HSC sources. In patients' PB and BM, slanDCs were
      identified from day +21, showing median frequencies comparable to healthy donors,
      donor origin and kinetics of recovery similar to mDCs, pDCs, and monocytes. Under
      cyclosporin treatment, slanDCs displayed a normal pattern of maturation, and
      maintained an efficient chemotactic activity and capacity of releasing tumour
      necrosis factor (TNF)-alpha upon lipopolysaccharide (LPS) stimulation. None the
      less, they were almost undetectable in GVHD tissue specimens, being present only
      in intestinal acute GVHD samples. slanDCs reconstitute early, being donor-derived
      and functionally competent. The absence of slanDCs from most of the GVHD-targeted
      tissue specimens seems to rule out the direct participation of these cells in the
      majority of the local reactions characterizing GVHD.

PMID- 24853273
TI  - Prediction of the determinants of thermal stability by linear discriminant
      analysis: the case of the glutamate dehydrogenase protein family.
AB  - Little is known about the determinants of thermal stability in individual protein
      families. Most of the knowledge on thermostability comes, in fact, from
      comparative analyses between large, and heterogeneous, sets of thermo- and
      mesophilic proteins. Here, we present a multivariate statistical approach aimed
      to detect signature sequences for thermostability in a single protein family. It
      was applied to the glutamate dehydrogenase (GDH) family, which is a good model
      for investigating this peculiar process. The structure of GDH consists of six
      subunits, each of them organized into two domains. Formation of ion-pair networks
      on the surface of the protein subunits, or increase in the inter-subunit
      hydrophobic interactions, have been suggested as important factors for explaining
      stability at high temperatures. However, identification of the amino acid changes
      that are involved in this process still remains elusive. Our approach consisted
      of a linear discriminant analysis on a set of GDH sequences from Archaea and
      Bacteria (33 thermo- and 36 mesophilic GDHs). It led to detection of 3 amino acid
      clusters as the putative determinants of thermal stability. They were localized
      at the subunit interface or in close proximity to the binding site of the
      NAD(P)(+) coenzyme. Analysis within the clusters led to prediction of 8 critical
      amino acid sites. This approach could have a wide utility, in the ligth of the
      notion that each protein family seems to adopt its own strategy for achieving
      thermostability. 

PMID- 24853274
TI  - Dynamics and control of foot-and-mouth disease in endemic countries: a pair
      approximation model.
AB  - Previous mathematical models of spatial farm-to-farm transmission of foot and
      mouth disease (FMD) have explored the impacts of control measures such as culling
      and vaccination during a single outbreak in a country normally free of FMD. As a
      result, these models do not include factors that are relevant to countries where
      FMD is endemic in some regions, like long-term waning natural and vaccine
      immunity, use of prophylactic vaccination and disease re-importations. These
      factors may have implications for disease dynamics and control, yet few models
      have been developed for FMD-endemic settings. Here we develop and study an SEIRV
      (susceptible-exposed-infectious-recovered-vaccinated) pair approximation model of
      FMD. We focus on long term dynamics by exploring characteristics of repeated
      outbreaks of FMD and their dependence on disease re-importation, loss of natural
      immunity, and vaccine waning. We find that the effectiveness of ring and
      prophylactic vaccination strongly depends on duration of natural immunity, rate
      of vaccine waning, and disease re-introduction rate. However, the number and
      magnitude of FMD outbreaks are generally more sensitive to the duration of
      natural immunity than the duration of vaccine immunity. If loss of natural
      immunity and/or vaccine waning happen rapidly, then multiple epidemic outbreaks
      result, making it difficult to eliminate the disease. Prophylactic vaccination is
      more effective than ring vaccination, at the same per capita vaccination rate.
      Finally, more frequent disease re-importation causes a higher cumulative number
      of infections, although a lower average epidemic peak. Our analysis demonstrates
      significant differences between dynamics in FMD-free settings versus FMD-endemic
      settings, and that dynamics in FMD-endemic settings can vary widely depending on
      factors such as the duration of natural and vaccine immunity and the rate of
      disease re-importations. We conclude that more mathematical models tailored to
      FMD-endemic countries should be developed that include these factors. 

PMID- 24853276
TI  - Catechin-based procyanidins from Peumus boldus Mol. aqueous extract inhibit
      Helicobacter pylori urease and adherence to adenocarcinoma gastric cells.
AB  - In this work, the anti-Helicobacter pylori effect of an aqueous extract from
      dried leaves of Peumus boldus Mol. (Monimiaceae) was evaluated. This extract
      displayed high inhibitory activity against H. pylori urease. Therefore, in order
      to clarify the type of substances responsible for such effect, a bioassay-guided
      fractionation strategy was carried out. The active compounds in the fractions
      were characterized through different chromatographic methods (RP-HPLC; HILIC
      HPLC). The fraction named F5 (mDP = 7.8) from aqueous extract was the most active
      against H. pylori urease with an IC50  = 15.9 ug gallic acid equivalents
      (GAE)/mL. HPLC analysis evidenced that F5 was composed mainly by catechin-derived
      proanthocyanidins (LC-MS and phloroglucinolysis). The anti-adherent effect of
      boldo was assessed by co-culture of H. pylori and AGS cells. Both the aqueous
      extract and F5 showed an anti-adherent effect in a concentration-dependent
      manner. An 89.3% of inhibition was reached at 2.0 mg GAE/mL of boldo extract. In
      conjunction, our results suggest that boldo extract has a potent anti-urease
      activity and anti-adherent effect against H. pylori, properties directly linked
      with the presence of catechin-derived proanthocyanidins.

PMID- 24853275
TI  - Influence of preoperative transcatheter arterial chemoembolization on gene
      expression in the HIF-1alpha pathway in patients with hepatocellular carcinoma.
AB  - PURPOSE: Although transcatheter arterial chemoembolization (TACE) is the most
      common treatment option in patients with hepatocellular carcinoma (HCC), its
      clinical benefits remain still controversial. Since TACE induces hypoxic necrosis
      in tumors, hypoxia-inducible factor 1alpha (HIF-1alpha) could critically affect
      biology in residual tumors after TACE treatment and subsequent prognosis.
      However, HIF-1alpha and its prognostic relevance in TACE have rarely been
      examined in human specimens. In the current study, we investigated the prognosis
      and expression of genes regulated by HIF-1alpha in HCC patients receiving
      preoperative TACE for the first time. METHODS: In total, 35 patients with HCC (10
      patients undergoing preoperative TACE) were retrospectively studied. The
      prognostic significance of TACE was analyzed using Kaplan-Meier and Cox
      regression models. Protein levels of HIF-1alpha and mRNA levels of HIF-1alpha
      associated genes were examined using immunohistochemistry (IHC) and real-time RT
      PCR, respectively. RESULTS: Preoperative TACE was significantly associated with
      increased 2-year recurrence rate (80 vs. 36 %, P = 0.00402) and shorter disease
      free survival (DFS) time (11.9 vs. 35.7 months, P = 0.0182). TACE was an
      independent prognostic factor for recurrence (P = 0.007) and poor DFS (P = 0.010)
      in a multivariate analysis. Immunohistochemical staining revealed in vivo
      activation of HIF-1alpha in human specimens treated with TACE. Notably, protein
      levels of HIF-1alpha were significantly increased in TACE tissues demonstrated by
      IHC. Transcriptional targets of HIF-1alpha showed mRNA expression patterns
      consistent with activation of HIF-1alpha in TACE tissues. CONCLUSIONS: Our
      findings collectively demonstrate that preoperative TACE confers poor prognosis
      in HCC patients through activation of HIF-1alpha.

PMID- 24853278
TI  - [PET in gliomas. Overview of current studies].
AB  - Gliomas which represent 30% of intracranial tumours are morphologic lesions and
      therefore CT and MRI are the first line diagnostic procedures with MRI giving
      better soft tissue resolution and permitting additional functional information.
      These mainly morphologic imaging modalities yield only restricted information on
      grade of malignancy, on infiltration into and effects on surrounding brain
      tissue, on differentiation between necrotic and recurrent tumour, on prognosis
      and on efficacy of treatment. Information on these important issues for patient
      management can be obtained by PET-studies of glucose metabolism with FDG, of
      aminoacid-uptake and protein synthesis with 11C-methionin, 18F-fluorethyltyrosin
      and 18F-fluor-deoxyphenylalanin and of proliferation by 18F-deoxythymidin. With
      the increasing availability of 18F-tracers PET has obtained wider spread clinical
      application. In all these applications a coregistration with morphologic imaging
      should be obtained, and for that purpose hybrid installations (PET-MR) are
      already being used. 

PMID- 24853277
TI  - A pilot phase I dose finding safety study of the thrombopoietin-receptor agonist,
      eltrombopag, in patients with myelodysplastic syndrome treated with azacitidine.
AB  - OBJECTIVES: Thrombocytopenia is an independent adverse prognostic factor in
      patients with Myelodysplastic syndromes (MDS). Azacitidine, first-line treatment
      for the majority of patients with higher-risk MDS, is associated with aggravated
      thrombocytopenia during the first cycles. Eltrombopag is a novel thrombopoietin
      receptor agonist, which also has been shown to inhibit proliferation of leukaemia
      cell lines in vitro. This phase I clinical trial was designed to explore the
      safety and tolerability of combining eltrombopag with azacitidine in patients
      with MDS. In addition, we assessed the potential effects of eltrombopag on
      hematopoietic stem and progenitor cells (HSPCs) from included patients. PATIENTS
      AND METHODS: Previously untreated patients with MDS eligible for treatment with
      azacitidine and with a platelet count <75 * 10(9) /L were included. Patients
      received eltrombopag in dose escalation cohorts during three cycles of
      azacitidine. RESULTS: Twelve patients, with a median age of 74 yr, were included.
      Severe adverse events included infectious complications, deep vein thrombosis and
      transient ischaemic attack. The maximal tolerated eltrombopag dose was 200 mg qd.
      Complete remission or bone marrow remission was achieved in 4 of 12 patients.
      Platelet counts improved or remained stable in 9 of 12 patients despite
      azacitidine treatment. No increase in blast count, disease progression, or bone
      marrow fibrosis related to study medication was reported. Eltrombopag did not
      induce cycling of HSPCs. CONCLUSION: The combination of eltrombopag with
      azacitidine in high-risk MDS patients is feasible and well tolerated.
      Improvements in platelet counts and the potential antileukaemic effect of
      eltrombopag should be explored in a randomised study.

PMID- 24853279
TI  - Differentially expressed microRNAs and affected signaling pathways in placentae
      of transgenic cloned cattle.
AB  - Placental deficiencies are related to the developmental abnormalities of
      transgenic cattle produced by somatic cell nuclear transfer, but the concrete
      molecular mechanism is not very clear. Studies have shown that placental
      development can be regulated by microRNAs (miRNAs) in normal pregnancy. Thus,
      this study screened differentially expressed miRNAs by the next-generation
      sequencing technology to reveal the relationship between miRNAs expression and
      aberrant development of placentae produced by the transgenic-clone technology.
      Expressions of miRNAs and mRNAs in different placentae were compared, the
      placentae derived from one natural pregnancy counterpart (PNC), one natural
      pregnancy of a cloned offspring as a mother (PCM), and two transgenic (human beta
      defensin-3) cloned pregnancy: one offspring was alive after birth (POL) and the
      other offspring was dead in 2 days after birth (POD). Further, signaling pathway
      analysis was conducted. The results indicated that 694 miRNAs were differentially
      expressed in four placental samples, such as miR-210, miR-155, miR-21, miR-128,
      miR-183, and miR-145. Signaling pathway analysis revealed that compared with PNC,
      significantly upregulated pathways in POL, POD, and PCM mainly included focal
      adhesion, extracellular matrix-receptor interaction, pathways in cancer,
      regulation of actin cytoskeleton, endosytosis, and adherens junction, and
      significantly downregulated pathways mainly included malaria, nucleotide binding
      oligomerization domain-like receptor signaling, cytokine-cytokine receptor
      interaction, Jak-STAT signaling pathway. In conclusion, this study confirmed
      alterations of the expression profile of miRNAs and signaling pathways in
      placentae from transgenic (hBD-3) cloned cattle (PTCC), which could lead to the
      morphologic and histologic deficiencies of PTCC. This information would be useful
      for the relative research in future.

PMID- 24853280
TI  - Goat oocyte quality and competence to undergo IVM and embryo development after
      parthenogenetic activation from goats fed with different levels of cashew nut
      bran as source of dietary lipids.
AB  - Lipid-rich and energy-dense diets can have significant effects on the
      reproductive physiology, including the ovarian function and fertility. The aim of
      this study was to assess the effect of cashew nut bran supplementation as a lipid
      source on follicle development, plasma and intrafollicular concentrations of
      cholesterol, and developmental competence of in vitro-matured goat oocytes. The
      inclusion of cashew nut bran as 24% of the goats' diet for 28 days increased the
      percentage and number of degenerated oocytes compared with the control (P <
      0.05), and also the plasma cholesterol levels and the proportion of grade IV
      oocytes compared with all other treatments (P < 0.05). Moreover, a significant
      reduction was observed in the proportion of viable oocytes compared with the
      control and in the percentage of grade II oocytes compared with all other
      treatments (P < 0.05). Oocyte maturation, cleavage, and blastocyst rates after
      parthenogenetic activation of viable oocytes were not affected by the type of
      diet. In conclusion, the inclusion of cashew nut bran as 24% of the diet of adult
      goats for 28 days changed plasma cholesterol levels and reduced the proportion of
      viable immature oocytes; however, the 12% and 24% diet supplementations with
      cashew nut bran did not interfere with competence of resulting viable oocytes to
      reach the metaphase II stage after IVM, and to develop after parthenogenetic
      activation.

PMID- 24853281
TI  - Generation and characterization of bat-induced pluripotent stem cells.
AB  - Induced pluripotent stem cells (iPSCs) were first generated from mouse embryonic
      fibroblasts in the year 2006. These cells resemble the typical morphology of
      embryonic stem cells, express pluripotency markers, and are able to transmit
      through germlines. To date, iPSCs of many species have been generated, whereas
      generation of bat iPSCs (biPSCs) has not been reported. To facilitate in-depth
      study of bats at the molecular and cellular levels, we describe the successful
      derivation of biPSCs with a piggyBac (PB) vector that contains eight
      reprogramming factors Oct4, Sox2, Klf4, Nanog, cMyc, Lin28, Nr5a2, and
      miR302/367. These biPSCs were cultured in media containing leukemia inhibitory
      factor and three small molecule inhibitors (CHIR99021, PD0325901, and A8301).
      They retained normal karyotype, displayed alkaline phosphatase activity, and
      expressed pluripotency markers Oct4, Sox2, Nanog, TBX3, and TRA-1-60. They could
      differentiate in vitro to form embryoid bodies and in vivo to form teratomas that
      contained tissue cells of all three germ layers. Generation of biPSCs will
      facilitate future studies on the mechanisms of antiviral immunity and longevity
      of bats at the cellular level.

PMID- 24853282
TI  - Arsenic and selenium toxicity and their interactive effects in humans.
AB  - Arsenic (As) and selenium (Se) are unusual metalloids as they both induce and
      cure cancer. They both cause carcinogenesis, pathology, cytotoxicity, and
      genotoxicity in humans, with reactive oxygen species playing an important role.
      While As induces adverse effects by decreasing DNA methylation and affecting
      protein 53 expression, Se induces adverse effects by modifying thioredoxin
      reductase. However, they can react with glutathione and S-adenosylmethionine by
      forming an As-Se complex, which can be secreted extracellularly. We hypothesize
      that there are two types of interactions between As and Se. At low concentration,
      Se can decrease As toxicity via excretion of As-Se compound [(GS3)2AsSe](-), but
      at high concentration, excessive Se can enhance As toxicity by reacting with S
      adenosylmethionine and glutathione, and modifying the structure and activity of
      arsenite methyltransferase. This review is to summarize their toxicity mechanisms
      and the interaction between As and Se toxicity, and to provide suggestions for
      future investigations. 

PMID- 24853283
TI  - Policy designs for cannabis legalization: starting with the eight Ps.
AB  - The cannabis policy landscape is changing rapidly. In November 2012 voters in
      Colorado and Washington State passed ballot initiatives to remove the prohibition
      on the commercial production, distribution, and possession of cannabis. This
      paper does not address the question of whether cannabis should be legal; it
      instead focuses on the design considerations confronting jurisdictions that are
      pondering a change in cannabis policy. Indeed, whether or not cannabis
      legalization is net positive or negative for public health and public safety
      largely depends on regulatory decisions and how they are implemented. This essay
      presents eight of these design choices which all conveniently begin with the
      letter "P": production, profit motive, promotion, prevention, potency, purity,
      price, and permanency.

PMID- 24853284
TI  - Escherichia coli viability determination using dynamic light scattering: a
      comparison with standard methods.
AB  - To determine the concentration of bacteria in a sample is important in the food
      industry, medicine and biotechnology. A disadvantage of the plate-counting method
      is that a microorganism colony could arise from one cell or from many cells. The
      other standard methodology, known as optical density determination, is based on
      the turbidity of a suspension and registers all bacteria, dead and alive. In this
      article, dynamic light scattering is proposed as a fast and reliable method to
      determine bacterial viability and, consequently, time evolution. Escherichia coli
      was selected because this microorganism is well known and easy to handle. A
      correlation between the data from these three techniques was obtained. We were
      able to calculate the growth rate, usually determined by plate counting or
      optical density measurement, using dynamic light scattering and to predict
      bacterial behavior. An analytical relationship between the colony forming units
      and the light scattered intensity was also deduced. 

PMID- 24853285
TI  - Over-expression of catalase in myeloid cells confers acute protection following
      myocardial infarction.
AB  - Cardiovascular disease is the leading cause of death in the United States and new
      treatment options are greatly needed. Oxidative stress is increased following
      myocardial infarction and levels of antioxidants decrease, causing imbalance that
      leads to dysfunction. Therapy involving catalase, the endogenous scavenger of
      hydrogen peroxide (H2O2), has been met with mixed results. When over-expressed in
      cardiomyocytes from birth, catalase improves function following injury. When
      expressed in the same cells in an inducible manner, catalase showed a time
      dependent response with no acute benefit, but a chronic benefit due to altered
      remodeling. In myeloid cells, catalase over-expression reduced angiogenesis
      during hindlimb ischemia and prevented monocyte migration. In the present study,
      due to the large inflammatory response following infarction, we examined myeloid
      specific catalase over-expression on post-infarct healing. We found a significant
      increase in catalase levels following infarction that led to a decrease in H2O2
      levels, leading to improved acute function. This increase in function could be
      attributed to reduced infarct size and improved angiogenesis. Despite these
      initial improvements, there was no improvement in chronic function, likely due to
      increased fibrosis. These data combined with what has been previously shown
      underscore the need for temporal, cell-specific catalase delivery as a potential
      therapeutic option. 

PMID- 24853286
TI  - Detection of a specific biomarker for Epstein-Barr virus using a polymer-based
      genosensor.
AB  - This paper describes methodology for direct and indirect detections of a specific
      oligonucleotide for Epstein-Barr virus (EBV) using electrochemical techniques.
      The sequence of oligonucleotide probe (EBV1) revealed a high sequence identity
      (100%) with the EBV genome. For the development of the genosensor, EBV1 was
      grafted to the platform sensitized with poly(4-aminothiophenol). After that, the
      hybridization reaction was carried out with the complementary target (EBV2) on
      the modified electrode surface using ethidium bromide as DNA intercalator. The
      oxidation peak currents of ethidium bromide increased linearly with the values of
      the concentration of the complementary sequences in the range from 3.78 to 756
      umol.L-1. In nonstringent experimental conditions, this genosensor can detect
      17.32 nmol.L-1 (three independent experiments) of oligonucleotide target,
      discriminating between complementary and non-complementary oligonucleotides, as
      well as differentiating one-base mismatch, as required for detection of genetic
      diseases caused by point mutations. The biosensor also displayed high specificity
      to the EBV target with elimination of interference from mix (alanine, glucose,
      uric acid, ascorbic acid, bovine serum albumin (BSA), glutamate and glycine) and
      good stability (120 days). In addition, it was possible to observe differences
      between hybridized and non-hybridized surfaces through atomic force microscopy.

PMID- 24853288
TI  - Green conversion of agroindustrial wastes into chitin and chitosan by Rhizopus
      arrhizus and Cunninghamella elegans strains.
AB  - This article sets out a method for producing chitin and chitosan by
      Cunninghamella elegans and Rhizopus arrhizus strains using a green metabolic
      conversion of agroindustrial wastes (corn steep liquor and molasses). The
      physicochemical characteristics of the biopolymers and antimicrobial activity are
      described. Chitin and chitosan were extracted by alkali-acid treatment, and
      characterized by infrared spectroscopy, viscosity and X-ray diffraction. The
      effectiveness of chitosan from C. elegans and R. arrhizus in inhibiting the
      growth of Listeria monocytogenes, Staphylococcus aureus, Pseudomonas aeruginosa,
      Salmonella enterica, Escherichia coli and Yersinia enterocolitica were evaluated
      by determining the minimum inhibitory concentrations (MIC) and the minimum
      bactericidal concentrations (MBC). The highest production of biomass (24.60 g/L),
      chitin (83.20 mg/g) and chitosan (49.31 mg/g) was obtained by R. arrhizus. Chitin
      and chitosan from both fungi showed a similar degree of deacetylation,
      respectively of 25% and 82%, crystallinity indices of 33.80% and 32.80% for
      chitin, and 20.30% and 17.80% for chitosan. Both chitin and chitosan presented
      similar viscosimetry of 3.79-3.40 cP and low molecular weight of 5.08*103 and
      4.68*103 g/mol. They both showed identical MIC and MBC for all bacteria assayed.
      These results suggest that: agricultural wastes can be produced in an
      environmentally friendly way; chitin and chitosan can be produced economically;
      and that chitosan has antimicrobial potential against pathogenic bacteria.

PMID- 24853289
TI  - A trivalent approach for determining in vitro toxicology: Examination of oxime
      K027.
AB  - Unforeseen toxic effects contribute to compound attrition during preclinical
      evaluation and clinical trials. Consequently, there is a need to correlate in
      vitro toxicity to in vivo and clinical outcomes quickly and effectively. We
      propose an expedited evaluation of physiological parameters in vitro that will
      improve the ability to predict in vivo toxicity of potential therapeutics. By
      monitoring metabolism, mitochondrial physiology and cell viability, our approach
      provides insight to the extent of drug toxicity in vitro. To implement our
      approach, we used human hepatocellular carcinoma cells (HepG2) and neuroblastoma
      cells (SH-SY5Y) to monitor hepato- and neurotoxicity of the experimental oxime
      K027. We utilized a trivalent approach to measure metabolism, mitochondrial
      stress and induction of apoptosis in 96-well formats. Any change in these three
      areas may suggest drug-induced toxicity in vivo. K027 and pralidoxime, an oxime
      currently in clinical use, had no effect on glycolysis or oxygen consumption in
      HepG2 and SH-SY5Y cells. Similarly, these oximes did not induce oxidant
      generation nor alter mitochondrial membrane potential. Further, K027 and
      pralidoxime failed to activate effector caspases, and these oximes did not alter
      viability. The chemotherapeutic agent, docetaxel, negatively affected metabolism,
      mitochondrial physiology and viability. Our studies present a streamlined high
      throughput trivalent approach for predicting toxicity in vitro, and this approach
      reveals that K027 has no measurable hepatotoxicity or neurotoxicity in vitro,
      which correlates with their in vivo data. This approach could eliminate toxic
      drugs from consideration for in vivo preclinical evaluation faster than existing
      toxicity prediction panels and ultimately prevent unnecessary experimentation.

PMID- 24853287
TI  - A pH and redox dual responsive 4-arm poly(ethylene glycol)-block-poly(disulfide
      histamine) copolymer for non-viral gene transfection in vitro and in vivo.
AB  - A novel 4-arm poly(ethylene glycol)-b-poly(disulfide histamine) copolymer was
      synthesized by Michael addition reaction of poly(ethylene glycol) (PEG) vinyl
      sulfone and amine-capped poly(disulfide histamine) oligomer, being denoted as 4
      arm PEG-SSPHIS. This copolymer was able to condense DNA into nanoscale polyplexes
      (<200 nm in average diameter) with almost neutral surface charge (+(5-10) mV).
      Besides, these polyplexes were colloidal stable within 4 h in HEPES buffer saline
      at pH 7.4 (physiological environment), but rapidly dissociated to liberate DNA in
      the presence of 10 mM glutathione (intracellular reducing environment). The
      polyplexes also revealed pH-responsive surface charges which markedly increased
      with reducing pH values from 7.4-6.3 (tumor microenvironment). In vitro
      transfection experiments showed that polyplexes of 4-arm PEG-SSPHIS were capable
      of exerting enhanced transfection efficacy in MCF-7 and HepG2 cancer cells under
      acidic conditions (pH 6.3-7.0). Moreover, intravenous administration of the
      polyplexes to nude mice bearing HepG2-tumor yielded high transgene expression
      largely in tumor rather other normal organs. Importantly, this copolymer and its
      polyplexes had low cytotoxicity against the cells in vitro and caused no death of
      the mice. The results of this study indicate that 4-arm PEG-SSPHIS has high
      potential as a dual responsive gene delivery vector for cancer gene therapy. 

PMID- 24853291
TI  - Observation of nano-dewetting in colloidal crystal drying.
AB  - The drying of colloidal crystals is connected with a continuous shrinkage
      process. However, several minutes after starting the drying, the system seems to
      take a breath before it shrinks monotonously until its final state after about
      one day. This short period we call "v"-event because of the shape of the curve
      characterizing the lattice constant: a decrease followed by a counter-intuitive
      increase which ends after one hour. This event is found in time-dependent optical
      spectra. It is assigned to the start of a nano-dewetting process occurring at the
      colloidal particles. 

PMID- 24853290
TI  - Pelvic digit: a rare lesion.

PMID- 24853292
TI  - Exercise-induced pulse wave velocity changes in untreated patients with essential
      hypertension: the effect of an angiotensin receptor antagonist.
AB  - This study investigates arterial stiffness changes after acute exercise in young
      patients with untreated, recently diagnosed grade I essential hypertension (UH)
      compared with normotensive (NT) individuals and the effect of antihypertensive
      treatment on this phenomenon. Study 1 consisted of 25 UH and 15 NT patients. UH
      patients who received treatment were included in study 2 and were followed-up
      after a 3-month treatment period with an angiotensin II receptor blocker. Aortic
      pulse wave velocity (PWV) was assessed at baseline, at maximal exercise, and at
      10, 30, and 60 minutes later. In UH patients, PWV increased significantly at
      maximal exercise and 10 and 30 minutes of recovery, despite blood pressure fall
      to baseline levels. No significant PWV changes were observed in NT patients. Post
      treatment PWV levels were significantly decreased and similar to those of NT
      patients. Arterial stiffness is impaired following high-intensity acute exercise
      even in the early stages of hypertension. Antihypertensive treatment ameliorates
      these effects. 

PMID- 24853293
TI  - Colonisation with methicillin-resistant Staphylococcus aureus prior to renal
      transplantation is associated with long-term renal allograft failure.
AB  - Renal transplant recipients are at an increased risk of developing Methicillin
      resistant Staphylococcus aureus due to their immunosuppressed status. Herein, we
      investigate the incidence of MRSA infection in patients undergoing renal
      transplantation and determine the effect of MRSA colonisation on renal allograft
      function and overall mortality. Between January 1st 2007 and December 31st 2012,
      1499 consecutive kidney transplants performed in our transplant unit and a
      retrospective 1:2 matched case-control study was performed on this patient
      cohort. The 1-, 3- and 5-year overall graft survival rates were 100%, 86% and
      78%, respectively, in MRSA positive recipients compared with 100%, 100% and 93%,
      respectively, in the control group (P < 0.05). The 1-, 3- and 5-year overall
      patient survival rates were 100%, 97% and 79%, respectively, in MRSA positive
      recipients compared with 100%, 100% and 95%, respectively, in the control group
      (P = 0.1). In a multiple logistic regression analysis, colonisation with MRSA pre
      operatively was an independent predictor for renal allograft failure at 5 years
      (hazard ratio: 4.6, 95% confidence interval: 1-30.7, P = 0.048). These findings
      demonstrate that the incidence of long-term renal allograft failure is
      significantly greater in this patient cohort compared with a matched control
      population. 

PMID- 24853294
TI  - Plasma-based proteomics reveals lipid metabolic and immunoregulatory
      dysregulation in post-stroke depression.
AB  - BACKGROUND: Post-stroke depression (PSD) is the most common psychiatric
      complication facing stroke survivors and has been associated with increased
      distress, physical disability, poor rehabilitation, and suicidal ideation.
      However, the pathophysiological mechanisms underlying PSD remain unknown, and no
      objective laboratory-based test is available to aid PSD diagnosis or monitor
      progression. METHODS: Here, an isobaric tags for relative and absolute
      quantitation (iTRAQ)-based quantitative proteomic approach was performed to
      identify differentially expressed proteins in plasma samples obtained from PSD,
      stroke, and healthy control subjects. RESULTS: The significantly differentiated
      proteins were primarily involved in lipid metabolism and immunoregulation. Six
      proteins associated with these processes--apolipoprotein A-IV (ApoA-IV),
      apolipoprotein C-II (ApoC-II), C-reactive protein (CRP), gelsolin, haptoglobin,
      and leucine-rich alpha-2-glycoprotein (LRG)--were selected for Western blotting
      validation. ApoA-IV expression was significantly upregulated in PSD as compared
      to stroke subjects. ApoC-II, LRG, and CRP expression were significantly
      downregulated in both PSD and HC subjects relative to stroke subjects. Gelsolin
      and haptoglobin expression were significantly dysregulated across all three
      groups with the following expression profiles: gelsolin, healthy
      control>PSD>stroke subjects; haptoglobin, stroke>PSD>healthy control.
      CONCLUSIONS: Early perturbation of lipid metabolism and immunoregulation may be
      involved in the pathophysiology of PSD. The combination of increased gelsolin
      levels accompanied by decreased haptoglobin levels shows promise as a plasma
      based diagnostic biomarker panel for detecting increased PSD risk in post-stroke
      patients.

PMID- 24853295
TI  - Fronto-limbic disconnection in bipolar disorder.
AB  - BACKGROUND: Bipolar disorder (BD) is a severe, disabling and life-threatening
      illness. Disturbances in emotion and affective processing are core features of
      the disorder with affective instability being paralleled by mood-congruent biases
      in information processing that influence evaluative processes and social
      judgment. Several lines of evidence, coming from neuropsychological and imaging
      studies, suggest that disrupted neural connectivity could play a role in the
      mechanistic explanation of these cognitive and emotional symptoms. The aim of the
      present study is to investigate the effective connectivity in a sample of bipolar
      patients. METHODS: Dynamic causal modeling (DCM) technique was used to study 52
      inpatients affected by bipolar disorders consecutively admitted to San Raffaele
      hospital in Milano and forty healthy subjects. A face-matching task was used as
      activation paradigm. RESULTS: Patients with BD showed a significantly reduced
      endogenous connectivity in the DLPFC to Amy connection. There was no significant
      group effect upon the endogenous connection from Amy to ACC, from ACC to Amy and
      from DLPFC to ACC. CONCLUSIONS: Both DLPFC and ACC are part of a network
      implicated in emotion regulation and share strong reciprocal connections with the
      amygdale. The pattern of abnormal or reduced connectivity between DLPFC and
      amygdala may reflect abnormal modulation of mood and emotion typical of bipolar
      patients.

PMID- 24853296
TI  - The economic burden of schizophrenia in Germany: a population-based retrospective
      cohort study using genetic matching.
AB  - OBJECTIVE: Prior studies to determine the economic consequences of schizophrenia
      have largely been undertaken in clinical settings with a small number of cases
      and have been unable to analyze effects across different age cohorts. The aim of
      this study is to investigate the burden of schizophrenia in Germany. METHODS:
      Costs, service utilization, and premature mortality attributable to schizophrenia
      were estimated for the year 2008 using a retrospective matched cohort design.
      Therefore, 26,977 control subjects as well as 9411 individuals with a confirmed
      diagnosis of schizophrenia were drawn from a sickness fund claims database. To
      reduce conditional bias, the non-parametric genetic matching method was employed.
      RESULTS: The final study population comprised 8224 matched pairs. The annual cost
      attributable to schizophrenia was ?11,304 per patient from the payers'
      perspective and ?20,609 from the societal perspective with substantial variations
      among age groups: direct medical expenses were highest among patients aged>65
      years, whereas younger individuals (<25 years) incurred the greatest non-medical
      costs. The annual burden of schizophrenia from the perspective of German society
      ranges between ?9.63 billion and ?13.52 billion. CONCLUSION: There are
      considerable differences in the distribution of costs and service utilization for
      schizophrenia. Because schizophrenia is characterized by an early age of onset
      and a long duration, research efforts should be targeted at particular
      populations to obtain the most beneficial outcomes, both clinically and
      economically.

PMID- 24853297
TI  - The SATISPSY-22: development and validation of a French hospitalized patients'
      satisfaction questionnaire in psychiatry.
AB  - OBJECTIVE: The aim of our study was to develop a specific French self
      administered instrument for measuring hospitalized patients' satisfaction in
      psychiatry based on exclusive patient point of view: the SATISPSY-22. METHODS:
      The development of the SATISPSY was undertaken in three steps: item generation,
      item reduction, and validation. The content of the SATISPSY was derived from 80
      interviews with patients hospitalized in psychiatry. Using item response and
      classical test theories, item reduction was performed in 2 hospitals on 270
      responders. The validation was based on construct validity, reliability, and some
      aspects of external validity. RESULTS: The SATISPSY contains 22 items describing
      6 dimensions (staff, quality of care, personal experience, information, activity,
      and food). The six-factor structure accounted for 78.0% of the total variance.
      Each item achieved the 0.40 standard for item-internal consistency, and the
      Cronbach's alpha coefficients were>0.70. Scores of dimensions were strongly
      positively correlated with Visual Analogue Scale scores. Significant associations
      with socioeconomic and clinical indicators showed good discriminant and external
      validity. INFIT statistics were ranged from 0.71 to 1.25. CONCLUSIONS: The
      SATISPSY-22 presents satisfactory psychometric properties, enabling patient
      feedback to be incorporated in a continuous quality health care improvement
      strategy.

PMID- 24853298
TI  - Indwelling pleural catheters.
AB  - Indwelling pleural catheters (IPC) are now established as one of the major tools
      for the management of recurrent pleural effusions. Their traditional role, which
      saw them only as second line treatment for malignant effusions, has now expanded.
      Recent evidence has not only suggested that they may be effectively employed as
      first-line therapy in some malignant cases, but that there is a wider spectrum of
      diseases which may be managed by their use. The majority of patients are likely
      to experience symptomatic benefit and some may also go on to achieve pleurodesis.
      IPCs are relatively simple to insert and maintain, and theoretically allow
      patients to be managed entirely as an outpatient, meaning that they are likely to
      be cost-effective in the longer term. They can also dramatically improve the
      quality of life in patients who have typically needed lengthy hospital admissions
      or who have terminal malignant disease.

PMID- 24853299
TI  - Lipocalin 2 modulates the cellular response to amyloid beta.
AB  - The production, accumulation and aggregation of amyloid beta (Abeta) peptides in
      Alzheimer's disease (AD) are influenced by different modulators. Among these are
      iron and iron-related proteins, given their ability to modulate the expression of
      the amyloid precursor protein and to drive Abeta aggregation. Herein, we describe
      that lipocalin 2 (LCN2), a mammalian acute-phase protein involved in iron
      homeostasis, is highly produced in response to Abeta1-42 by choroid plexus
      epithelial cells and astrocytes, but not by microglia or neurons. Although Abeta1
      42 stimulation decreases the dehydrogenase activity and survival of wild-type
      astrocytes, astrocytes lacking the expression of Lcn2 are not affected. This
      protection results from a lower expression of the proapoptotic gene Bim and a
      decreased inflammatory response. Altogether, these findings show that Abeta
      toxicity to astrocytes requires LCN2, which represents a novel mechanism to
      target when addressing AD. 

PMID- 24853301
TI  - Cytokine gene polymorphisms and severity of CF lung disease.
AB  - BACKGROUND: The search for modifier genes to explain inconsistencies in cystic
      fibrosis (CF) genotype-phenotype relationships has yielded mixed results. In a
      previous cross-sectional study from our centre the clinical effect (as described
      by FEV1, BMI z-score, admitted days and NIH score) of single nucleotide
      polymorphisms (SNPs) of four cytokine genes (IL-8, TNF-alpha, IL-1beta and IL-10)
      was examined in 158 children with CF. No association between cytokine genotype
      and any biological outcome measure was found. In this present study a cross
      sectional and longitudinal examination of this relationship was undertaken to
      test the hypothesis that pro-inflammatory SNPs would affect longitudinal changes
      in CF lung disease. METHODS: Using the cohort examined in our earlier study we
      performed both longitudinal and cross-sectional data analyses examining the
      relationship between SNPs (TNF-alpha, IL-8, IL-10 and IL-1beta) and clinical
      outcome measurements. In the first part of this current study, lung function data
      (annual decline of FEV1 percent predicted) was compared with the cytokine
      genotype over a 13 year period. In the second part of this current study multiple
      regression was used to assess associations between clinical outcomes (best FEV1
      percent predicted and BMI at the age of 10 years) and alleles of cytokine genes,
      adjusting for gender, CF genotype and lung infection status. RESULTS: A total of
      152 patients with CF were analysed in the longitudinal study and data from 130
      patients at the age of 10 years were analysed in the cross-sectional study. There
      was evidence for an association between pro-inflammatory SNPs of the IL-8, IL-10
      and IL-1beta genes and more severe lung disease. Multiple regression of the
      longitudinal data with a total of 10,956 lung function measurements showed an
      additional annual decline of the percentage predicted FEV1 of -1.15 (IL-8,
      p<0.001), -0.24 (IL-10, p=0.049) and -0.41 (IL-1beta, p<0.001) for patients with
      any of the pro-inflammatory alleles. None of the cross-sectional data showed a
      significant association between the cytokine genotypes and the clinical outcomes.
      CONCLUSION: Pro-inflammatory alleles of three cytokine genotypes, IL-8, IL-10 and
      IL-1beta, appear to be associated with slightly more severe lung disease in
      patients with CF over a 13 year period. Further studies are required to exclude
      influence of confounders on the severity of lung disease.

PMID- 24853300
TI  - Crucial role of calbindin-D28k in the pathogenesis of Alzheimer's disease mouse
      model.
AB  - Calbindin-D28k (CB), one of the major calcium-binding and buffering proteins, has
      a critical role in preventing a neuronal death as well as maintaining calcium
      homeostasis. Although marked reductions of CB expression have been observed in
      the brains of mice and humans with Alzheimer disease (AD), it is unknown whether
      these changes contribute to AD-related dysfunction. To determine the pathogenic
      importance of CB depletions in AD models, we crossed 5 familial AD mutations
      (5XFAD; Tg) mice with CB knock-out (CBKO) mice and generated a novel line
      CBKO.5XFAD (CBKOTg) mice. We first identified the change of signaling pathways
      and differentially expressed proteins globally by removing CB in Tg mice using
      mass spectrometry and antibody microarray. Immunohistochemistry showed that
      CBKOTg mice had significant neuronal loss in the subiculum area without changing
      the magnitude (number) of amyloid beta-peptide (Abeta) plaques deposition and
      elicited significant apoptotic features and mitochondrial dysfunction compared
      with Tg mice. Moreover, CBKOTg mice reduced levels of phosphorylated mitogen
      activated protein kinase (extracellular signal-regulated kinase) 1/2 and cAMP
      response element-binding protein at Ser-133 and synaptic molecules such as N
      methyl-D-aspartate receptor 1 (NMDA receptor 1), NMDA receptor 2A, PSD-95 and
      synaptophysin in the subiculum compared with Tg mice. Importantly, this is the
      first experimental evidence that removal of CB from amyloid precursor
      protein/presenilin transgenic mice aggravates AD pathogenesis, suggesting that CB
      has a critical role in AD pathogenesis. 

PMID- 24853302
TI  - Anacardic acid induces cell apoptosis associated with induction of ATF4-dependent
      endoplasmic reticulum stress.
AB  - Anacardic acid (6-pentadecylsalicylic acid, AA), a natural compound isolated from
      the traditional medicine Amphipterygium adstringens, has been reported to possess
      antitumor activities. However, its molecular targets have not been thoroughly
      studied. Here, we report that AA is a potent inducer of endoplasmic reticulum
      (ER) stress, leading to apoptosis in hepatoma HepG2 and myeloma U266 cells.
      Induction of ER stress by AA was supported by a dose- and time-dependent increase
      in expression of the ER signaling downstream molecules, such as GRP78/BiP,
      phosphorylated eIF2alpha, ATF4 and CHOP in both HepG2 and U266 cell lines.
      Blockage of ATF4 expression by siRNA partially inhibited, while knockdown of CHOP
      expression by siRNA slightly increased AA-induced cell death in these cells. In
      addition, AA suppressed HepG2 xenograft tumor growth, associated with increased
      ER stress in vivo. These results suggest that AA induces tumor cell apoptosis
      associated with ATF4-dependent ER stress. 

PMID- 24853303
TI  - Green synthesis of low-toxicity graphene-fulvic acid with an open band gap
      enhances demethylation of methylmercury.
AB  - The demethylation of methylmercury has received substantial attention. Here, a
      novel chemical method for the demethylation of methylmercury is proposed. The low
      toxicity graphene-fulvic acid (FA, a ubiquitous material in the environment) was
      synthesized without the use of a chemical reagent. The hybridized graphene-FA
      presented an indirect open band gap of 2.25-2.87 eV as well as adequate aqueous
      dispersion. More importantly, the hybridized graphene-FA exhibited 6- and 10-fold
      higher photocatalytic efficiencies for the demethylation of methylmercury than FA
      and free FA with graphene, respectively. This result implies that immobilized,
      rather than free, FA accelerated the catalysis. Furthermore, inorganic mercuric
      ion, elemental mercury, and mercuric oxide were identified as the primary
      demethylation products. For free FA with graphene, graphene quenches the excited
      state FA, inhibiting the demethylation by electron transfer. In contrast, the
      graphene of the self-assembled graphene-FA serves as an electron reservoir,
      causing electron-hole pair separation. Graphene-FA showed a negligible toxicity
      toward microalgae compared to graphene. The above results reveal that the green
      synthesis of graphene and organic molecules is a convenient strategy for
      obtaining effective cocatalysts. 

PMID- 24853305
TI  - Stabilizing incidence of hepatitis C virus infection among men who have sex with
      men in Amsterdam.

PMID- 24853304
TI  - WHO multicenter evaluation of FACSCount CD4 and Pima CD4 T-cell count systems:
      instrument performance and misclassification of HIV-infected patients.
AB  - BACKGROUND: CD4+ T-cell counts are used to screen and follow-up HIV-infected
      patients during treatment. As part of the World Health Organization
      prequalification program of diagnostics, we conducted an independent multicenter
      evaluation of the FACSCount CD4 and the Pima CD4, using the FACSCalibur as
      reference method. METHODS: A total of 440 paired capillary and venous blood
      samples were collected from HIV-infected patients attending the HIV outpatient
      clinic in Antwerp, Belgium, and the HIV care and treatment center in Dar es
      Salam, Tanzania. Capillary blood was run on Pima analyzer, whereas venous blood
      was analyzed on FACSCount, Pima, and FACSCalibur instruments. Precision and
      agreement between methods were assessed. RESULTS: The FACSCount CD4 results were
      in agreement with the FACSCalibur results with relative bias of 0.4% and 3.1% on
      absolute CD4 counts and an absolute bias of -0.6% and -1.1% on CD4% in Antwerp
      and Dar es Salam, respectively. The Pima CD4 results were in agreement with the
      FACSCalibur results with relative bias of -4.1% and -9.4% using venous blood and
      of -9.5% and -0.9% using capillary blood in Antwerp and Dar es Salam,
      respectively. At the threshold of 350 cells per microliter, the FACSCount CD4 and
      Pima CD4 using venous and capillary blood misclassified 7%, 9%, and 13% of
      patients, respectively. CONCLUSIONS: The FACSCount CD4 provides reliable CD4
      counts and CD4% and is suitable for monitoring adult and pediatric HIV patients
      in moderate-volume settings. The Pima CD4 is more suitable for screening eligible
      adult HIV patients for antiretroviral treatment initiation in low-volume
      laboratories.

PMID- 24853306
TI  - Study product adherence measurement in the iPrEx placebo-controlled trial:
      concordance with drug detection.
AB  - OBJECTIVE: To evaluate the concordance between adherence estimated by self-report
      (in-person interview or computer-assisted self-interview), in-clinic pill counts,
      and pharmacy dispensation records and drug detection among participants in a
      placebo-controlled pre-exposure prophylaxis HIV prevention trial (iPrEx). DESIGN:
      Cross-sectional evaluation of 510 participants who had drug concentration data
      and matched adherence assessments from their week-24 study visit. METHODS: Self
      reported adherence collected through (1) interview and (2) computer-assisted self
      interview surveys, (3) adherence estimated by pill count, and (4) medication
      possession ratio was contrasted to having a detectable level of drug
      concentrations [either tenofovir diphosphate (TFV-DP) or emtricitabine
      triphosphate (FTC-TP)], as well as to having evidence of consistent dosing
      (tenofovir diphosphate >= 16 fmol/106 cells), focusing on positive predictive
      values, overall and by research site. RESULTS: Overall, self-report and pharmacy
      records suggested high rates of product use (over 90% adherence); however, large
      discrepancies between these measures and drug detection were noted, which varied
      considerably between sites (positive predictive values from 34% to 62%). Measures
      of adherence performed generally well in the US sites but had poor accuracy in
      other research locations. Medication possession ratio outperformed other measures
      but still had relatively low discrimination. CONCLUSIONS: The sizable discrepancy
      between adherence measures and drug detection in certain regions highlights the
      potential contribution of factors that may have incentivized efforts to seem
      adherent. Understanding the processes driving adherence reporting in some
      settings, but not others, is essential for finding effective ways to increase
      accuracy in measurement of product use and may generalize to promotion efforts
      for open-label pre-exposure prophylaxis.

PMID- 24853308
TI  - Impact of isoniazid preventive therapy for HIV-infected adults in Rio de Janeiro,
      Brazil: an epidemiological model.
AB  - BACKGROUND: The potential epidemiological impact of isoniazid preventive therapy
      (IPT), delivered at levels that could be feasibly scaled up among people living
      with HIV (PLHIV) in modern, moderate-burden settings, remains uncertain. METHODS:
      We used routine surveillance and implementation data from a cluster-randomized
      trial of IPT among HIV-infected clinic patients with good access to
      antiretroviral therapy in Rio de Janeiro, Brazil, to populate a parsimonious
      transmission model of tuberculosis (TB)/HIV. We modeled IPT delivery as a
      constant process capturing a proportion of the eligible population every year. We
      projected feasible reductions in TB incidence and mortality in the general
      population and among PLHIV specifically at the end of 5 years after implementing
      an IPT program. RESULTS: Data on time to IPT fit an exponential curve well,
      suggesting that IPT was delivered at a rate covering 20% (95% confidence
      interval: 16% to 24%) of the 2500 eligible individuals each year. By the end of
      year 5 after modeled program rollout, IPT had reduced TB incidence by 3.0% [95%
      uncertainty range (UR): 1.6% to 7.2%] in the general population and by 15.6% (95%
      UR: 15.5% to 36.5%) among PLHIV. Corresponding reductions in TB mortality were
      4.0% (95% UR: 2.2% to 10.3%) and 14.3% (14.6% to 33.7%). Results were robust to
      wide variations in parameter values on sensitivity analysis. CONCLUSIONS: TB
      screening and IPT delivery can substantially reduce TB incidence and mortality
      among PLHIV in urban, moderate-burden settings. In such settings, IPT can be an
      important component of a multi-faceted strategy to feasibly reduce the burden of
      TB in PLHIV.

PMID- 24853307
TI  - Reliability and validity of depression assessment among persons with HIV in sub
      Saharan Africa: systematic review and meta-analysis.
AB  - OBJECTIVE: The aim of this study was to systematically review the reliability and
      validity of instruments used to screen for major depressive disorder or assess
      depression symptom severity among persons with HIV in sub-Saharan Africa. DESIGN:
      Systematic review and meta-analysis. METHODS: A systematic evidence search
      protocol was applied to 7 bibliographic databases. Studies examining the
      reliability and/or validity of depression assessment tools were selected for
      inclusion if they were based on the data collected from HIV-positive adults in
      any African member state of the United Nations. A random-effects meta-analysis
      was used to calculate pooled estimates of depression prevalence. In a subgroup of
      studies of criterion-related validity, the bivariate random-effects model was
      used to calculate pooled estimates of sensitivity and specificity. RESULTS: Of
      1117 records initially identified, I included 13 studies of 5373 persons with HIV
      in 7 sub-Saharan African countries. Reported estimates of Cronbach alpha ranged
      from 0.63 to 0.95, and analyses of internal structure generally confirmed the
      existence of a depression-like construct accounting for a substantial portion of
      variance. The pooled prevalence of probable depression was 29.5% [95% confidence
      interval (CI): 20.5 to 39.4], whereas the pooled prevalence of major depressive
      disorder was 13.9% (95% CI: 9.7 to 18.6). The Center for Epidemiologic Studies
      Depression scale was the most frequently studied instrument, with a pooled
      sensitivity of 0.82 (95% CI: 0.73 to 0.87) for detecting major depressive
      disorder. CONCLUSIONS: Depression-screening instruments yielded relatively high
      false positive rates. Overall, few studies described the reliability and/or
      validity of depression instruments in sub-Saharan Africa.

PMID- 24853309
TI  - Safety of cotrimoxazole in pregnancy: a systematic review and meta-analysis.
AB  - INTRODUCTION: Cotrimoxazole is widely prescribed to treat a range of infections,
      and for HIV-infected individuals it is administered as prophylaxis to protect
      against opportunistic infections. Some reports suggest that fetuses exposed to
      cotrimoxazole during early pregnancy may have an increased risk of congenital
      anomalies. We carried out this systematic review to update the evidence of
      cotrimoxazole safety in pregnancy. METHODS: Three databases and 1 conference
      abstract site were searched in duplicate up to October 31, 2013, for studies
      reporting adverse maternal and infant outcomes among women receiving
      cotrimoxazole during pregnancy. This search was updated in MEDLINE via PubMed to
      April 28, 2014. Studies were included irrespective of HIV infection status or the
      presence of other coinfections. Our primary outcome was birth defects of any
      kind. Secondary outcomes included spontaneous abortions, terminations of
      pregnancy, stillbirths, preterm deliveries, and drug-associated toxicity.
      RESULTS: Twenty-four studies were included for review. There were 232 infants
      with congenital anomalies among 4196 women receiving cotrimoxazole during
      pregnancy, giving an overall pooled prevalence of 3.5% (95% confidence interval:
      1.8% to 5.1%; tau2 = 0.03). Three studies reported 31 infants with neural tube
      defects associated with first trimester exposure to cotrimoxazole, giving a crude
      prevalence of 0.7% (95% confidence interval: 0.5% to 1.0%) with most data (29
      neural tube defects) coming from a single study. The majority of adverse drug
      reactions were mild. The quality of the evidence was very low. CONCLUSIONS: The
      findings of this review support continued recommendations for cotrimoxazole as a
      priority intervention for HIV-infected pregnant women. It is critical to improve
      data collection on maternal and infant outcomes.

PMID- 24853310
TI  - Correlates of suboptimal entry into early infant diagnosis in rural north central
      Nigeria.
AB  - BACKGROUND: Despite an estimated 59,000 incident pediatric HIV infections in 2012
      in Nigeria, rates of early infant diagnosis (EID) of HIV service uptake remain
      low. We evaluated maternal factors independently associated with EID uptake in
      rural North Central Nigeria. METHODS: We performed a cohort study using HIV/AIDS
      program data of HIV-infected pregnant women enrolled into HIV care/treatment on
      or before December 31, 2012 (n = 712). We modeled the probability of initiation
      of EID using multivariable logistic regression. RESULTS: Three hundred fifty
      seven HIV-infected pregnant women enrolled their infants in EID across the 4
      study sites. Women who enrolled their infants in EID vs. those who did not were
      similar across age, occupation, referral source, and select laboratory variables.
      Clinic of enrollment and date of enrollment were strong predictors for EID entry
      (P < 0.001). Women enrolled more recently were less likely to have their infants
      undergo EID than those enrolled at the beginning of the project (January 2011 vs.
      January 2010, adjusted odds ratio = 0.35, 95% confidence interval: 0.22 to 0.56;
      January 2012 vs. January 2010, adjusted odds ratio = 0.30, 95% confidence
      interval: 0.14 to 0.61). Women who received care in the more urban setting of
      Umaru Yar Adua Hospital were more likely to have their infants enrolled in EID
      than those who received care in the other 3 clinics. CONCLUSIONS: HIV-infected
      women in our prevention of mother-to-child HIV transmission program were more
      likely to bring in their infants for EID if they were enrolled in a more
      urbanized clinic location, and if they presented during an earlier phase of the
      program. The need for more intensive family engagement and program quality
      improvement is apparent, especially in rural settings.

PMID- 24853311
TI  - An intervention to support HIV preexposure prophylaxis adherence in HIV
      serodiscordant couples in Uganda.
AB  - BACKGROUND: Daily preexposure prophylaxis (PrEP) is an effective HIV prevention
      strategy, but adherence is required for maximum benefit. To date, there are no
      empirically supported PrEP adherence interventions. This article describes the
      process of developing a PrEP adherence intervention and presents results on its
      impact on adherence. METHODS: The Partners PrEP Study was a placebo-controlled
      efficacy trial of daily oral tenofovir and emtricitabine/tenofovir PrEP among
      uninfected members of HIV-serodiscordant couples. An ancillary adherence study
      was conducted at 3 study sites in Uganda. Participants with <80% adherence as
      measured by unannounced pill count received an additional adherence counseling
      intervention based on Lifesteps, an evidence-based HIV treatment adherence
      intervention, based on principles of cognitive-behavioral theory. FINDINGS: Of
      the 1147 HIV-seronegative participants enrolled in the ancillary adherence study,
      168 (14.6%) triggered the adherence intervention. Of participants triggering the
      intervention, 62% were men; median age was 32.5 years. The median number of
      adherence counseling sessions was 10. Mean adherence during the month before the
      intervention was 75.7% and increased significantly to 84.1% in the month after
      the first intervention session (P < 0.001). The most frequently endorsed
      adherence barriers at session 1 were travel and forgetting. INTERPRETATION: A
      PrEP adherence intervention was feasible in a clinical trial of PrEP in Uganda
      and PrEP adherence increased after the intervention. Future research should
      identify PrEP users with low adherence for enhanced adherence counseling and
      determine optimal implementation strategies for interventions to maximize PrEP
      effectiveness.

PMID- 24853313
TI  - Rational design and characterization of the novel, broad and potent bispecific
      HIV-1 neutralizing antibody iMabm36.
AB  - BACKGROUND: Although broadly neutralizing monoclonal antibodies (bNAbs) have
      always been considered to be a potential therapeutic option for the prophylaxis
      and treatment of HIV infection, their lack of breadth against all HIV variants
      has been one of the limiting factors. To provide sufficient neutralization
      breadth and potency against diverse viruses, including neutralization escape
      mutants, strategies to combine different bNAbs have been explored recently.
      METHODS: We rationally designed and engineered a novel bispecific HIV-1
      neutralizing antibody (bibNAb), iMabm36. The potency and breadth of iMabm36
      against HIV were extensively characterized in vitro. RESULTS: iMabm36 comprises
      the anti-CD4 Ab ibalizumab (iMab) linked to 2 copies of the single-domain Ab m36,
      which targets a highly conserved CD4-induced epitope. iMabm36 neutralizes a
      majority of a large, multiclade panel of pseudoviruses (96%, n = 118) at an IC50
      concentration of less than 10 ug/mL, with 83% neutralized at an IC50
      concentration of less than 0.1 ug/mL. In addition, iMabm36 neutralizes a small
      panel of replication-competent transmitted-founder viruses to 100% inhibition at
      a concentration of less than 0.1 ug/mL in a peripheral blood mononuclear cell
      based neutralizing assay. Mechanistically, the improved antiviral activity of
      iMabm36 is dependent on both the CD4-binding activity of the iMab component and
      the CD4i-binding activity of the m36 component. After characterizing that viral
      resistance to iMabm36 neutralization was due to mutations residing in the
      bridging sheet of gp120, an optimized m36 variant was engineered that, when fused
      to iMab, improved antiviral activity significantly. CONCLUSIONS: The
      interdependency of this dual mechanism of action enables iMabm36 to potently
      inhibit HIV-1 entry. These results demonstrate that mechanistic-based design of
      bibNAbs can generate potential preventive and therapeutic candidates for
      HIV/AIDS.

PMID- 24853315
TI  - What influences referral to 12-step mutual self-help groups by treatment
      professionals?
AB  - BACKGROUND/AIMS: Twelve-step mutual self-help groups provide cost-effective
      support for recovery from substance misuse problems. Evidence suggests they are
      successful as an adjunct to formal treatment and that referral from clinicians is
      important in fostering engagement. METHODS: This study surveyed substance misuse
      treatment professionals employed within two agencies in Birmingham (UK). RESULTS:
      A total of 92 clinicians (79.3%) eligible to participate completed a
      questionnaire that explored their attitudes, knowledge and referral practices
      with regard to 12-step groups (TSGs). Most (74%) had a positive attitude, and
      almost 80% referred at least some of their clients to TSGs. However, 30% had not
      referred any clients in the past month, and multivariate analysis showed that
      referral was associated with greater objective knowledge about TSGs when other
      factors were controlled for. CONCLUSIONS: These results have implications for
      linking professional treatment to mutual self-help groups, and potential
      strategies to increase referral are discussed.

PMID- 24853314
TI  - Ultrasound-guided rectus sheath block or wound infiltration in children: a
      randomized blinded study of analgesia and bupivacaine absorption.
AB  - BACKGROUND: Rectus sheath block can provide analgesia following umbilical hernia
      repair. However, conflicting reports on its analgesic effectiveness exist. No
      study has investigated plasma local anesthetic concentration following ultrasound
      guided rectus sheath block (USGRSB) in children. OBJECTIVES: Compare the
      effectiveness and bupivacaine absorption following USGRSB or wound infiltration
      (WI) for umbilical hernia repair in children. METHODS: A randomized blinded study
      comparing WI with USGRSB in 40 children undergoing umbilical hernia repair was
      performed. Group WI (n = 20) received wound infiltration 1 mg.kg(-1) 0.25%
      bupivacaine. Group RS (n = 20) received USGRSB 0.5 mg.kg(-1) 0.25% bupivacaine
      per side in the posterior rectus sheath compartment. Pain scores and rescue
      analgesia were recorded. Blood samples were drawn at 0, 10, 20, 30, 45, and 60
      min. RESULTS: Patients in the WI group had a twofold increased risk of requiring
      morphine (hazard ratio 2.06, 95% CI 1.01, 4.20, P = 0.05). When required, median
      time to first morphine dose was longer in the USGRSB group (65.5 min vs. 47.5
      min, P = 0.049). Peak plasma bupivacaine concentration was higher following
      USGRSB than WI (median: 631.9 ng.ml(-1) IQR: 553.9-784.1 vs. 389.7 ng.ml(-1) IQR:
      250.5-502.7, P = 0.002). Tmax was longer in the USGRSB group (median 45 min IQR:
      30-60 vs. 20 min IQR: 20-45, P = 0.006). CONCLUSIONS: USGRSB provides more
      effective analgesia than WI for umbilical hernia repair. USGRSB with 1 mg.kg(-1)
      0.25% bupivacaine is associated with safe plasma bupivacaine concentration that
      peaks higher and later than WI. Caution against using larger volumes of higher
      concentration local anesthetic for USGRSB is advised.

PMID- 24853312
TI  - Relationship between hyperglycemia and the risk of tuberculosis in Asian HIV
      positive individuals in the antiretroviral therapy era: cohort study.

PMID- 24853317
TI  - Modified forward model for eliminating the time-varying impact in fluorescence
      molecular tomography.
AB  - In conventional fluorescence molecular tomography, the distribution of
      fluorescent contrast agents is reconstructed with the assumption of constant
      concentration during data acquisition for each image frame. However, the
      concentration of fluorescent contrast target is usually time-varying in
      experiments or in-vivo studies. In this case, the reconstruction methods cannot
      be directly applied to the fluorescence measurements without considering the time
      varying effects of concentration. We propose a modified forward model by dividing
      the fluorescence yield distribution into two parts: one is a constant
      representing the spatial distribution of the fluorescent target and the other is
      an impact factor representing the effects of the concentration change and other
      possible factors. By extracting spatial distribution information from the
      reconstruction result, the location and volume of the fluorescent target can be
      obtained accurately. Both simulation and phantom experiments are carried out and
      the results indicate that, by using the modified forward model, the quality of
      reconstruction could be significantly improved in terms of accurate localization
      and strong anti-noise ability.

PMID- 24853316
TI  - Decay theory of immediate memory: From Brown (1958) to today (2014).
AB  - This work takes a historical approach to discussing Brown's (1958) paper, "Some
      Tests of the Decay Theory of Immediate Memory". This work was and continues to be
      extremely influential in the field of forgetting over the short term. Its primary
      importance is in establishing a theoretical basis to consider a process of
      fundamental importance: memory decay. Brown (1958) established that time-based
      explanations of forgetting can account for both memory capacity and forgetting of
      information over short periods of time. We discuss this view both in the context
      of the intellectual climate at the time of the paper's publication and in the
      context of the modern intellectual climate. The overarching theme we observe is
      that decay is as controversial now as it was in the 1950s and 1960s. 

PMID- 24853318
TI  - Capsule endoscopic findings correlate with fecal calprotectin and C-reactive
      protein in patients with suspected small-bowel Crohn's disease.
AB  - OBJECTIVE: Capsule endoscopy (CE) is a sensitive method for detecting
      inflammatory lesions in the small bowel. Such lesions may be due to Crohn's
      disease but also to other causes and a histological diagnosis may be difficult to
      achieve in the small bowel. The aim of the study was to find a possible
      correlation between capsule endoscopic findings, biochemical parameters, and
      symptoms in patients with suspected or known small-bowel Crohn's disease.
      MATERIALS AND METHODS: Thirty patients with inflammatory lesions in the small
      bowel diagnosed by CE were included. CE findings of inflammation were graded
      using the Lewis score. C-reactive protein (CRP) and fecal calprotectin were used
      as biochemical parameters. Symptoms were graded using the Harvey-Bradshaw index.
      The patients were followed up after 9 months with a second CE, CRP, fecal
      calprotectin, and Harvey-Bradshaw index. RESULTS: There was a significant
      persistent correlation between endoscopic inflammation and fecal calprotectin (p
      = 0.003 at inclusion and p < 0.001 at follow-up). CRP was correlated to
      endoscopic inflammation at inclusion (p = 0.006), but not at follow-up. Symptoms
      were not correlated with endoscopic inflammation. CONCLUSION: Inflammatory
      lesions in the small bowel diagnosed by CE in patients with suspected Crohn's
      disease are correlated to fecal calprotectin and CRP, but not to symptoms.

PMID- 24853319
TI  - Non-contact in vivo measurement of ocular microtremor using laser speckle
      correlation metrology.
AB  - Ocular microtremor (OMT) is a small involuntary eye movement present in all
      subjects. In this paper we present the results of in vivo OMT measurement using a
      novel non-contact laser speckle technique. OMT signals have not previously been
      measured from the sclera using this laser speckle correlation technique. To
      verify the system's ability to record eye movements, it is first tested using a
      large angle eye rotation. Next, the system is tested with a group of 20 subjects
      and OMT parameters are extracted. The results of OMT measurements gave a mean
      frequency of 78 +/- 3.86 Hz and peak-to-peak amplitude of 21.42 +/- 7.01 urad,
      these values are consistent with known values from eye-contacting methods. 

PMID- 24853320
TI  - Amino derivatives of glycyrrhetinic acid as potential inhibitors of
      cholinesterases.
AB  - The development of remedies against the Alzheimer's disease (AD) is one of the
      biggest challenges in medicinal chemistry nowadays. Although not completely
      understood, there are several strategies fighting this disease or at least
      bringing some relief. During the progress of AD, the level of acetylcholine (ACh)
      decreases; hence, a therapy using inhibitors should be of some benefit to the
      patients. Drugs presently used for the treatment of AD inhibit the two ACh
      controlling enzymes, acetylcholinesterase as well as butyrylcholinesterase;
      hence, the design of selective inhibitors is called for. Glycyrrhetinic acid
      seems to be an interesting starting point for the development of selective
      inhibitors. Although its glycon, glycyrrhetinic acid is known for being an AChE
      activator, several derivatives, altered in position C-3 and C-30, exhibited
      remarkable inhibition constants in micro-molar range. Furthermore, five
      representative compounds were subjected to three more enzyme assays (on carbonic
      anhydrase II, papain and the lipase from Candida antarctica) to gain information
      about the selectivity of the compounds in comparison to other enzymes. In
      addition, photometric sulforhodamine B assays using murine embryonic fibroblasts
      (NiH 3T3) were performed to study the cytotoxicity of these compounds. Two
      derivatives, bearing either a 1,3-diaminopropyl or a 1H-benzotriazolyl residue,
      showed a BChE selective inhibition in the single-digit micro-molar range without
      being cytotoxic up to 30MUM. In silico molecular docking studies on the active
      sites of AChE and BChE were performed to gain a molecular insight into the mode
      of action of these compounds and to explain the pronounced selectivity for BChE. 

PMID- 24853321
TI  - Synthesized quercetin derivatives stimulate melanogenesis in B16 melanoma cells
      by influencing the expression of melanin biosynthesis proteins MITF and p38 MAPK.
AB  - In order to understand the effect of structure-activity relationships on
      melanogenesis using B16 melanoma cells, 19 quercetin derivatives were
      synthesized. Among the synthesized compounds, 3-O-methylquercetin (11) and
      3',4',7-O-trimethylquercetin (14) increased melanin content more potently than
      the positive control theophylline, while exhibiting low cytotoxicity. Compound 11
      exhibited less melanogenesis-stimulating activity than compound 14. However, 11
      increased the expression of tyrosinase and tyrosinase-related protein 1 (TRP-1)
      to a greater extent than 14, thereby suggesting that melanogenesis in melanoma
      cells does not depend solely on the expression of the enzymes catalyzing melanin
      biosynthesis. Furthermore, 14 also stimulated the expression of the
      microphthalmia-associated transcription factor (MITF) and p-p38 mitogen activated
      protein kinase (MAPK), while they were not increased by 11. These results suggest
      that 11 may enhance the expression of tyrosinase and TRP-1 by regulating the
      proteasomal degradation of melanogenic enzymes and/or by activating other
      transcriptional factors regulating enzyme expression. 

PMID- 24853322
TI  - New rhenium complexes with ciprofloxacin as useful models for understanding the
      properties of [99mTc]-ciprofloxacin radiopharmaceutical.
AB  - Rhenium complexes with the antibiotic ciprofloxacin have been prepared to be
      studied as models of technetium radiopharmaceuticals. With this aim, the new
      rhenium complexes 1 {[ReO(Cpf)2]Cl}, 2 {[ReO(CpfH)2]Cl3} and 3 {fac
      [Re(CO)3(H2O)(Cpf)]} with ciprofloxacin (CpfH=ciprofloxacin; Cpf=conjugated base
      of ciprofloxacin) have been synthesised and characterised by elemental analyses,
      IR, NMR ((1)H, (19)F and (13)C CP-MAS) spectroscopy, as well as MS measurements.
      All spectroscopic data are consistent with the coordination of ciprofloxacin in
      all these complexes through the carbonyl and the carboxylate oxygen atoms with
      the formation of a six member chelate ring. The study of a Tc-ciprofloxacin
      solution by ESI-MS reveals the presence of [TcO(Cpf)2](+) cations, which agrees
      with the hypothesis that complexes 1 and 2 can be seen as model rhenium complexes
      of this radiopharmaceutical. Antimicrobial and DNA gyrase inhibition studies
      performed with complexes 2 and 3 have shown a very similar behaviour between
      complex 2 and the free antibiotic, whereas complex 3 exhibit a lower
      antimicrobial activity. Based on a joint analysis of the data reported in the
      literature and the chemical and biological results obtained in this study, a
      tentative proposal to explain some aspects of the behaviour of Tc-ciprofloxacin
      radiopharmaceutical has been made. 

PMID- 24853325
TI  - A call for uniformity and collectivism.

PMID- 24853323
TI  - Identification and characterization of a new reversible MAGL inhibitor.
AB  - Monoacylglycerol lipase is a serine hydrolase that play a major role in the
      degradation of 2-arachidonoylglycerol, an endocannabinoid neurotransmitter
      implicated in several physiological processes. Recent studies have shown the
      possible role of MAGL inhibitors as anti-inflammatory, anti-nociceptive and anti
      cancer agents. The use of irreversible MAGL inhibitors determined an unwanted
      chronic MAGL inactivation, which acquires a functional antagonism function of the
      endocannabinoid system. However, the application of reversible MAGL inhibitors
      has not yet been explored, mainly due to the scarcity of known compounds
      possessing efficient reversible inhibitory activities. In this study we reported
      the first virtual screening analysis for the identification of reversible MAGL
      inhibitors. Among the screened compounds, the (4-(4-chlorobenzoyl)piperidin-1
      yl)(4-methoxyphenyl)methanone (CL6a) is a promising reversible MAGL inhibitor
      lead (Ki=8.6MUM), which may be used for the future development of a new class of
      MAGL inhibitors. Furthermore, the results demonstrate the validity of the
      methodologies that we followed, encouraging additional screenings of other
      commercial databases. 

PMID- 24853324
TI  - Two pink nodules in a patient with acute myeloid leukemia.

PMID- 24853327
TI  - Percutaneous ultrasonography as imaging modality and sampling guide for
      pulmonologists.
AB  - Ultrasound (US) imaging is gradually progressing into common practice in
      contemporary pulmonology. Its main applications are to determine the presence and
      amount of pleural effusions and to guide subsequent treatment interventions.
      Guidelines recommend the use of US for these indications. Training programs are
      organized and competency levels are formulated. Image guidance with US to obtain
      specimens for pathologic and/or microbiological analysis is less extensively
      practiced by pulmonologists but it is an important tool for tumour staging and
      diagnosing diseases. Lung tumours in contact with the pleural surface, pleural
      thickenings, mediastinal tumours and chest wall tumours are conceivable
      indications for pulmonologists to approach with the help of US visualization.
      Moreover, sampling of chest disease-related extrathoracal lesions may also be
      regarded as the working field of the pulmonologist. For example, supraclavicular
      and axillar lymph node metastasis, and also soft tissue and bone metastases, are
      lesions encountered during dissemination tests. US-guided biopsy provides not
      only a diagnosis, but also gives information on the stage of disease in sometimes
      inaccessible primary lesions. US-guided sampling increases diagnostic efficacy
      and safety and enables very precise performance of fine-needle aspirations as
      well as tissue core biopsies.

PMID- 24853328
TI  - Crystal engineering of zeolites with graphene.
AB  - Achieving control over the morphology of zeolite crystals at the nanoscale is
      crucial for enhancing their performance in diverse applications including
      catalysis, sensors and separation. The complexity and sensitivity of zeolite
      synthesis processes, however, often make such control both highly empirical and
      difficult to implement. We demonstrate that graphene can significantly alter the
      morphology of titanium silicalite (TS-1) particles, in particular being able to
      reduce their dimensions from several hundreds to less than 10 nm. Through
      electron microscopy and molecular mechanics simulations we propose a mechanism
      for this change based on the preferential interaction of specific TS-1 surfaces
      with benzyl-alcohol-mediated graphene. These findings suggest a facile new means
      of controlling the zeolite morphology and thereby also further demonstrate the
      potential of graphene in hybrid materials. Moreover, the generality of the
      mechanism points the way to a new avenue of research in using two-dimensional
      materials to engineer functional inorganic crystals. 

PMID- 24853329
TI  - Ionic size dependent electroviscous effects in ion-selective nanopores.
AB  - Pressure-driven flows of aqueous ionic liquids are characterized by
      electroviscosity-an increase in the effective (apparent) viscosity because of an
      induced back electric field termed streaming potential. In this work, we
      investigate the electrokinetic phenomenon of streaming potential mediated flows
      in ion-selective nanopores. We report a dramatic augmentation in the effective
      viscosity as attributable to the finite size effect of the ionic species in
      counterion-only systems. The underlying physics involves complex interaction
      between the concerned electrochemical phenomena and hydrodynamic transport in a
      confined fluidic environment, which we capture through a modified continuum based
      approach and validate using molecular dynamics simulations. We obtain an
      expression for the ionic-size dependent streaming potential pertinent to the
      physical situation being addressed. The corresponding estimations of effective
      viscosity implicate that the classical paradigm of point sized ions can give rise
      to gross underestimations of the flow resistance in counterion-only systems
      especially for negligible surface (Stern layer) conductivity and large fluidic
      slip at the surface. 

PMID- 24853330
TI  - A mechanistic study of the Lewis base-directed cycloaddition of 2-pyrones and
      alkynylboranes.
AB  - Significant rate enhancements in the Diels-Alder reaction of alkynes and 2
      pyrones bearing a Lewis basic group are observed when a combination of
      alkynyltrifluoroborates and BF3.OEt2 is used. This process generates
      functionalized aromatic compounds with complete regiocontrol. The observed rate
      enhancement was studied by density functional theory methods and appears to
      originate from coordination of the diene substrate to a mixture of alkynylborane
      intermediates, followed by a Lewis acid-mediated product equilibration step.
      Evidence for this mechanism is presented, as is the enhanced promotion of the
      cycloaddition via the use of alternative Lewis acid promoters. 

PMID- 24853331
TI  - The habenulo-interpeduncular and mammillothalamic tracts: early developed fiber
      tracts in the human fetal diencephalon.
AB  - PURPOSE: The habenulo-interpeduncular (HI) and mammillothalamic (MT) tracts are
      phylogenetically ancient. The clinical relevance of these tracts has recently
      received attention. In this work, we map the anatomy the developing HI and MT.
      METHODS: To investigate the topographical anatomy of developing fiber tracts in
      and around the diencephalon, we examined the horizontal, frontal, and sagittal
      serial paraffin sections of 28 human fetuses at 8-12 weeks of gestation. RESULTS:
      In all specimens, eosinophilic early fiber bundles were limited to the bilateral
      HI and MT tracts in contrast to pale-colored later developing fibers such as the
      thalamocortical projections and optic tract. The HI and MT tracts ran nearly
      parallel and sandwiched the thalamus from the dorsal and ventral sides,
      respectively. The nerve tract course appeared to range from 5-7 mm for the HI
      tract and 3-5 mm for the MT tract in 15 specimens at 11-12 weeks. The HI tract
      was embedded in, adjacent to, or distant from the developing parvocellular red
      nucleus. CONCLUSIONS: In early human fetuses, HI and MT tracts might be limited
      pathways for primitive cholinergic fiber connections between the ventral midbrain
      and epithalamic limbic system.

PMID- 24853333
TI  - The history of endometriosis.
AB  - A dispute has recently emerged whether early descriptions exist of the condition
      we name endometriosis. A first question is: 'Who identified endometriosis?' To
      respond, two non-complementary methods have been employed: searching for ancient
      descriptions of symptoms associated with endometriosis or, alternatively,
      identifying researchers who described pathological features we associate with the
      presence of endometriosis in its various forms. We opted for the latter and found
      no evidence that in older times anyone delineated the macroscopic features of
      endometriosis; descriptions of menstrual or cyclic pain cannot be taken as proof
      of knowledge of what caused it. During the mid-part of the 19th century,
      Rokitansky had a great intuition: endometrial glands and stroma can be present in
      ovarian and uterine neoplasias. However, using histological parameters of
      endometrial structure and activity, the first scientist to delineate peritoneal
      endometriosis under the name 'adenomyoma' was Cullen. On the other hand,
      Rokitansky was the first to describe a form of adenomyosis (an adenomatous
      polyp). Early descriptions of ovarian endometrioma as 'haematomas of the ovary'
      or 'chocolate cysts' date back to the end of the 19th century. The first mention
      of an 'ovary containing uterine mucosa' was published in 1899 by Russel, but
      Sampson was the first to demonstrate specific endometrial activities, such as
      desquamation at the time of menstruation and decidualization in pregnancy;
      subsequently, he presented a theory on its pathogenesis.

PMID- 24853332
TI  - Correlating brain volume and callosal thickness with clinical and laboratory
      indicators of disease severity in children with HIV-related brain disease.
AB  - BACKGROUND: Objective MRI markers of central nervous system disease severity may
      precede subjective features of HIV encephalopathy in children. Previous work in
      HIV-infected adults shows that brain atrophy was associated with low CD4 and with
      neuropsychological impairment. Significant thinning of the corpus callosum (CC),
      predominantly anteriorly, was also found in HIV-infected adults and correlated
      with CD4 levels. These findings have not been tested in children. PURPOSE: The
      aim of this study was to determine if brain volume and midsagittal CC linear
      measurements (thickness and length) on MRI in children with HIV-related brain
      disease correlate with clinical and laboratory parameters of disease severity.
      METHODS: Retrospective MRI analysis in children with HIV-related brain disease
      used a volumetric analysis software and a semi-automated tool to measure brain
      volume and callosal thickness/length, respectively. Each measure was correlated
      with clinical parameters of disease severity including Griffiths Mental
      Development scores (GMDS), absolute CD4 counts (cells/mm(3)), nadir CD4 (the
      lowest CD4 recorded, excluding baseline), duration of HAART, and decreased brain
      growth. RESULTS: Thirty-three children with HIV-related brain disease were
      included. Premotor segment of the CC mean thickness correlated with age (p =
      0.394). Motor CC maximum thickness correlated significantly with general
      developmental quotient (p = 0.0277); CC length correlated with a diagnosis of
      acquired microcephaly (p = 0.0071) and to CD4 level closest to date of the MRI
      scan (p = 0.04). CONCLUSIONS: Length of the CC and the "motor CC segment" may
      represent surrogate clinical biomarkers of central nervous system disease
      severity and with decreased level of immunity in HIV-infected patients that
      precede established HIV encephalopathy.

PMID- 24853334
TI  - Current and future greenhouse gas emissions associated with electricity
      generation in China: implications for electric vehicles.
AB  - China's oil imports and greenhouse gas (GHG) emissions have grown rapidly over
      the past decade. Addressing energy security and GHG emissions is a national
      priority. Replacing conventional vehicles with electric vehicles (EVs) offers a
      potential solution to both issues. While the reduction in petroleum use and hence
      the energy security benefits of switching to EVs are obvious, the GHG benefits
      are less obvious. We examine the current Chinese electric grid and its evolution
      and discuss the implications for EVs. China's electric grid will be dominated by
      coal for the next few decades. In 2015 in Beijing, Shanghai, and Guangzhou, EVs
      will need to use less than 14, 19, and 23 kWh/100 km, respectively, to match the
      183 gCO2/km WTW emissions for energy saving vehicles. In 2020, in Beijing,
      Shanghai, and Guangzhou EVs will need to use less than 13, 18, and 20 kWh/100 km,
      respectively, to match the 137 gCO2/km WTW emissions for energy saving vehicles.
      EVs currently demonstrated in China use 24-32 kWh/100 km. Electrification will
      reduce petroleum imports; however, it will be very challenging for EVs to
      contribute to government targets for GHGs emissions reduction. 

PMID- 24853335
TI  - Structural basis for histone mimicry and hijacking of host proteins by influenza
      virus protein NS1.
AB  - Pathogens can interfere with vital biological processes of their host by
      mimicking host proteins. The NS1 protein of the influenza A H3N2 subtype
      possesses a histone H3K4-like sequence at its carboxyl terminus and has been
      reported to use this mimic to hijack host proteins. However, this mimic lacks a
      free N-terminus that is essential for binding to many known H3K4 readers. Here we
      show that the double chromodomains of CHD1 adopt an 'open pocket' to interact
      with the free N-terminal amine of H3K4, and the open pocket permits the NS1 mimic
      to bind in a distinct conformation. We also explored the possibility that NS1
      hijacks other cellular proteins and found that the NS1 mimic has access to only a
      subset of chromatin-associated factors, such as WDR5. Moreover, methylation of
      the NS1 mimic can not be reversed by the H3K4 demethylase LSD1. Overall, we thus
      conclude that the NS1 mimic is an imperfect histone mimic. 

PMID- 24853337
TI  - Diastereomeric preference of a triply axial chiral binaphthyl based molecule: a
      concentration dependent study by chiroptical spectroscopies.
AB  - We have examined the effects of environmental perturbations, specifically
      solvents and concentrations, on axial chirality of a recently synthesized axially
      chiral binaphthyl fluorene based salen ligand, named AFX-155, {[2,2'-(1E,1'E)-(R)
      1,1'-binaphthyl-2,2'-diylbis(azan-1-yl-1-ylidene)bis(methan-1-yl-1-ylidene)bis(4
      ((7-(diphenylamino)-9,9-dihexyl-9H-fluoren-2-l)ethynyl)-phenol)]}. Chirality and
      dominant conformations of AFX-155 in CDCl3 solvent have been characterized using
      vibrational absorption (VA) and vibrational circular dichroism (VCD) spectroscopy
      in combination with DFT calculations. AFX-155 exhibits triple axial chirality:
      one is at the binaphthyl ring and the other two are related to the axes of
      chirality along the -C-N bonds where Cs are part of the binaphthyl group. To
      evaluate solvent and concentration dependence, complementary VA and VCD
      experiments in both THF-d8 and CDCl3 have been performed, as well as the optical
      rotatory dispersion (ORD) and electronic CD (ECD) measurements in CDCl3 under
      much diluted conditions. While the binaphthyl chirality is determined by the
      synthetic route, the results show that the latter two axial chirality labels of
      the dominant diastereomers are concentration dependent. Under much diluted
      conditions, R-binaphthyl, R_intra_HB//R_extra_HB (R-RR) is favoured, whereas R
      binaphthyl, S_intra_HB//S_extra_HB (R-SS) is the dominant species in a
      concentrated solution. This diastereomeric interconversion is found to be
      independent of the two solvents used. To provide insights into this interesting
      finding, conformational searches and the related spectral simulations have been
      carried out at the DFT/B3LYP/6-31G(d) level. 

PMID- 24853336
TI  - Ultrafast spontaneous emission of copper-doped silicon enhanced by an optical
      nanocavity.
AB  - Dopants in silicon (Si) have attracted attention in the fields of photonics and
      quantum optics. However, the optical characteristics are limited by the small
      spontaneous emission rate of dopants in Si. This study demonstrates a large
      increase in the spontaneous emission rate of copper isoelectronic centres (Cu
      IECs) doped into Si photonic crystal nanocavities. In a cavity with a quality
      factor (Q) of ~16,000, the photoluminescence (PL) lifetime of the Cu-IECs is 1.1
      ns, which is 30 times shorter than the lifetime of a sample without a cavity. The
      PL decay rate is increased in proportion to Q/Vc (Vc is the cavity mode volume),
      which indicates the Purcell effect. This is the first demonstration of a cavity
      enhanced ultrafast spontaneous emission from dopants in Si, and it may lead to
      the development of fast and efficient Si light emitters and Si quantum optical
      devices based on dopants with efficient optical access. 

PMID- 24853338
TI  - [An atypical Stafne cavity-multi-chamber bone lesion with bucal expansion. A case
      report].
AB  - In the literature Stafne bone cavities are mostly described for male patients in
      their fifth and sixth decade. Usually the lingual cavities appear as ovoid
      lesions located unilateral in the molar region of the lower jaw underneath the
      inferior alveolar nerve. Classically they contain parts of the submandibular
      gland. This case study describes a patient who was referred to the authors?
      clinic with a cavity in the right lower jaw extending over a mesio-distal
      diameter of 24 mm. Its appearance on panoramic x-ray and cone beam computer
      tomography (CTBT) was inconclusive. The diagnosis could finally be made after
      magnetic resonance imaging (MRI). It was based on the content of gland, fat and
      lymphatic tissue in a lingual open cavity, which is a characteristic feature of
      Stafne bone cavities. Assumed aetiology and differential diagnosis are discussed.

PMID- 24853339
TI  - The relevance of the chemokine receptor ACKR3/CXCR7 on CXCL12-mediated effects in
      cancers with a focus on virus-related cancers.
AB  - Recent studies have highlighted the importance of understanding the molecular
      determinants of CXCL12-mediated effects in cancers. Once previously thought to
      interact exclusively with CXCR4, CXCL12 also binds with high affinity to CXCR7
      (recently renamed ACKR3), which belongs to an atypical chemokine receptor family
      whose members fail to activate Galphai proteins but interact with beta-arrestins.
      In addition to its capacity to control CXCL12 bioavailability, ACKR3 can either
      enhance or dampen CXCR4-mediated signaling and activity. In light of the most
      recent findings, we have examined the role of ACKR3 in cancer, including a subset
      of virus-related cancers. 

PMID- 24853340
TI  - The role of bone morphogenetic proteins in myeloma cell survival.
AB  - Multiple myeloma is characterized by slowly growing clones of malignant plasma
      cells in the bone marrow. The malignant state is frequently accompanied by
      osteolytic bone disease due to a disturbed balance between osteoblasts and
      osteoclasts. Bone morphogenetic proteins (BMPs) are present in the bone marrow
      and are important for several aspects of myeloma pathogenesis including growth
      and survival of tumor cells, bone homeostasis, and anemia. Among cancer cells,
      myeloma cells are particularly sensitive to growth inhibition and apoptosis
      induced by BMPs and therefore represent good models to study BMP receptor usage
      and signaling. Our review highlights and discusses the current knowledge on BMP
      signaling in myeloma. 

PMID- 24853341
TI  - Investigation of the effect of different polishing techniques on the surface
      roughness of denture base and repair materials.
AB  - STATEMENT OF PROBLEM: The rough surface of denture base materials may cause
      plaque accumulation and staining. Thus, the effectiveness of polishing techniques
      should be known. PURPOSE: The purpose of this study was to compare the effects of
      chairside polishing kits and conventional laboratory techniques on the surface
      roughness of denture base and repair materials. MATERIAL AND METHODS: Ninety-six
      specimens, 50 +/-1 mm in diameter and 0.5 +/-0.05 thick, were fabricated from
      heat-polymerized acrylic resin (HP), polyamide resin (PR), and autopolymerizing
      resin (AP) and submitted to grinding with a tungsten carbide bur. The specimens
      were divided into 4 groups according to the polishing technique used: control
      group without polishing, conventional laboratory polishing, polished with Acrylic
      Polisher HP blue kit, and polished with AcryPoint polishing kit. Surface
      roughness (Ra) was measured after polishing with a profilometer. Data were
      analyzed with a 2-way analysis of variance, and the Tukey honestly significant
      difference (HSD) test was performed to identify significant differences
      (alpha=.05). RESULTS: The polishing techniques significantly affected the Ra of
      denture base materials (P<.001). The highest mean average Ra was measured for the
      control group. The lowest Ra values were determined in specimens exposed to
      conventional laboratory polishing techniques. No significant differences were
      found between Acrylic Polisher HP blue and AcryPoint polishing kits (P>.05).
      Statistically significant differences were found in the Ra between the PR and
      both the HP and AP (P<.001); PR exhibited the highest Ra values. CONCLUSIONS:
      Conventional laboratory polishing was the most effective polishing technique. A
      significantly smoother surface than that of the specimens in the control group
      was produced with chairside silicone polishing kits.

PMID- 24853342
TI  - Combined vaginal-cesarean delivery of twins: risk factors and neonatal outcome--a
      single center experience.
AB  - OBJECTIVE: We aimed to characterize risk factors for combined twin delivery and
      assess neonatal outcome. METHODS: This was a retrospective cohort study of all
      women admitted for trial of labor (TOL) with twin gestation, in a single,
      tertiary, university-affiliated medical center. Eligibility was limited to
      gestations with twin A delivered vaginally. RESULTS: During the study period, 44
      263 women delivered in our center, of whom 1307 (2.9%) delivered twins. Overall,
      221 out of 247 women (89.5%) undergoing TOL delivered twin A vaginally.
      Parturients who delivered twin B by cesarean delivery (n = 23) were compared with
      those delivered twin B vaginally (n = 198). Multivariate analysis demonstrated
      that risk factors combined delivery were included non-cephalic twin B at
      admission (aOR 11.5, 95% CI 3.8-34.9, p < 0.001) or after delivery of twin A (aOR
      17.7, 95% CI 6.6-47.2, p < 0.001), and dichorionic-diamniotic (DCDA) twins (aOR
      8.9, 95% CI 1.8-44.0, p = 0.008). Spontaneous version of a cephalic twin B was
      not found to increase the risk (above the baseline risk of non-cephalic twin B)
      for combined delivery. Combined delivery was associated with slightly higher risk
      for hemorrhagic-ischemic encephalopathy of twin B (4.3% versus 0%, p = 0.003).
      CONCLUSION: Non-cephalic twin B at admission or following delivery of twin A
      poses higher risk for combined delivery. Neonatal outcome of twin B following
      combined delivery are comparable with those of vaginal delivery.

PMID- 24853343
TI  - Development of an enzyme-linked-receptor assay based on Syrian hamster beta2
      adrenergic receptor for detection of beta-agonists.
AB  - beta-Adrenergic agonists (beta-agonists) are illegally used in animal husbandry,
      threatening the health of consumers. To realize multianalyte detection of beta
      agonists, a beta2-adrenergic receptor (beta2-AR) was cloned from Syrian hamster
      lung and heterogeneously expressed by Spodoptera frugiperda (Sf9) cells. The
      recombinant beta2-AR was purified from intracellular soluble proteins of infected
      Sf9 cells, and was utilized to establish an enzyme-linked-receptor assay (ELRA)
      to detect a group of beta-agonists simultaneously. This assay was based on direct
      competitive inhibition of binding of horseradish peroxidase-labeled ractopamine
      to the immobilized beta2-AR proteins by beta-agonists. The IC50 and limit of
      detection values for ractopamine were 30.38MUgL(-1) and 5.20MUgL(-1),
      respectively. Clenbuterol and salbutamol showed 87.7% and 58.5% cross
      reactivities with ractopamine, respectively. This assay is simple, rapid, and
      environmentally friendly, showing a potential application in the screening of
      beta-agonists in animal feeds. 

PMID- 24853345
TI  - H4H - hydration for health.

PMID- 24853344
TI  - A fast automated screening method for the detection of blood transfusion in
      sports.
AB  - Currently, there is no simple direct screening method for the misuse of blood
      transfusions in sports. In this study, we investigated whether the measurement of
      iron in EDTA-plasma can serve as biomarker for such purpose. Our results revealed
      an increase of the plasma iron level up to 25-fold 6 h after blood re-infusion.
      The variable remained elevated 10-fold one day after the procedure. A specificity
      of 100% and a sensitivity of 93% were obtained with a proposed threshold at 45
      ug/dL of plasma iron. Therefore, our test could be used as a simple, cost
      effective biomarker for the screening for blood transfusion misuse in sports.

PMID- 24853346
TI  - From state to process: defining hydration.

PMID- 24853347
TI  - Optimal hydration biomarkers: consideration of daily activities.

PMID- 24853348
TI  - Hydration and kidney health.

PMID- 24853349
TI  - Obesity: a gateway disease with a rising prevalence.

PMID- 24853350
TI  - Hydration and obesity prevention.

PMID- 24853351
TI  - Design and construction of acetyl-CoA overproducing Saccharomyces cerevisiae
      strains.
AB  - Saccharomyces cerevisiae has increasingly been engineered as a cell factory for
      efficient and economic production of fuels and chemicals from renewable
      resources. Notably, a wide variety of industrially important products are derived
      from the same precursor metabolite, acetyl-CoA. However, the limited supply of
      acetyl-CoA in the cytosol, where biosynthesis generally happens, often leads to
      low titer and yield of the desired products in yeast. In the present work,
      combined strategies of disrupting competing pathways and introducing heterologous
      biosynthetic pathways were carried out to increase acetyl-CoA levels by using the
      CoA-dependent n-butanol production as a reporter. By inactivating ADH1 and ADH4
      for ethanol formation and GPD1 and GPD2 for glycerol production, the glycolytic
      flux was redirected towards acetyl-CoA, resulting in 4-fold improvement in n
      butanol production. Subsequent introduction of heterologous acetyl-CoA
      biosynthetic pathways, including pyruvate dehydrogenase (PDH), ATP-dependent
      citrate lyase (ACL), and PDH-bypass, further increased n-butanol production.
      Recombinant PDHs localized in the cytosol (cytoPDHs) were found to be the most
      efficient, which increased n-butanol production by additional 3 fold. In total, n
      butanol titer and acetyl-CoA concentration were increased more than 12 fold and 3
      fold, respectively. By combining the most effective and complementary acetyl-CoA
      pathways, more than 100mg/L n-butanol could be produced using high cell density
      fermentation, which represents the highest titer ever reported in yeast using the
      clostridial CoA-dependent pathway. 

PMID- 24853353
TI  - Polysaccharide nanofibers with variable compliance for directing cell fate.
AB  - Cells perceive their microenvironment through physical and mechanical cues, such
      as extracellular matrix topography or stiffness. In this study, we developed a
      polysaccharide scaffold that can provide combined substrate topography and matrix
      compliance signals to direct cell fate. Pullulan/dextran (P/D) nanofibers were
      fabricated with variable stiffness by in situ crosslinking during
      electrospinning. By varying the chemical crosslinking content between 10, 12, 14,
      and 16%, (denoted as STMP10, STMP12, STMP14, and STMP16 respectively), scaffold
      mechanical stiffness was altered. We characterized substrate stiffness by various
      methods. Under hydrated conditions, atomic force microscopy and tensile tests of
      bulk scaffolds were conducted. Under dry conditions, tensile tests of scaffolds
      and single nanofibers were examined. In addition, we evaluated the efficacy of
      the scaffolds in directing stem cell differentiation. Using human first trimester
      mesenchymal stem cells (fMSCs) cultured on STMP14 P/D scaffolds (Young's modulus:
      7.84 kPa) in serum-free neuronal differentiation medium exhibited greatest extent
      of differentiation. Cells showed morphological changes and significantly higher
      expression of motor neuron markers. Further analyses by western blotting also
      revealed the enhanced expression of choline acetyltransferase on STMP14 (7.84
      kPa) and STMP16 (11.08 kPa) samples as compared to STMP12 (7.19 kPa). Taken
      together, this study demonstrates that the stiffness of P/D nanofibers can be
      altered by differential in situ crosslinking during electrospinning and suggests
      the feasibility of using such polysaccharide nanofibers in supporting fMSC
      neuronal commitment.

PMID- 24853354
TI  - From water to aquaretics: a legendary route.
AB  - Man is water. When life appeared on earth, the primordial cell had a simple
      structure and could immediately ascertain from the surrounding aquatic
      environment the substances for nutrition and oxygen, without any need for
      structural complexity. As part of evolution, during the transition from aquatic
      to terrestrial life, vertebrates had to fight against dehydration as well as fish
      in the sea. In this complex mechanism of osmoregulation, the structure and
      function of some osmoregulatory hormones have been maintained during the
      evolution of species, from fish to man. Within the homeostatic mechanism, the
      renin-angiotensin-aldosterone system (RAAS) is crucial in the regulation of renal
      reasorption of water and sodium. It is also involved in the regulation of renal
      plasma flux, blood volume and blood pressure. Vasopressin plays a hormonal
      function in the mechanisms of water homeostasis acting through Aquaporins (AQP),
      channel-proteins that allow bi-directional water transport across cell membranes.

PMID- 24853355
TI  - Control of emission colour with N-heterocyclic carbene (NHC) ligands in
      phosphorescent three-coordinate Cu(I) complexes.
AB  - A series of three phosphorescent mononuclear (NHC)-Cu(I) complexes were prepared
      and characterized. Photophysical properties were found to be largely controlled
      by the NHC ligand chromophore. Variation of the NHC ligand leads to emission
      colour tuning over 200 nm range from blue to red, and emission efficiencies of
      0.16-0.80 in the solid state.

PMID- 24853352
TI  - Model based engineering of Pichia pastoris central metabolism enhances
      recombinant protein production.
AB  - The production of recombinant proteins is frequently enhanced at the levels of
      transcription, codon usage, protein folding and secretion. Overproduction of
      heterologous proteins, however, also directly affects the primary metabolism of
      the producing cells. By incorporation of the production of a heterologous protein
      into a genome scale metabolic model of the yeast Pichia pastoris, the effects of
      overproduction were simulated and gene targets for deletion or overexpression for
      enhanced productivity were predicted. Overexpression targets were localized in
      the pentose phosphate pathway and the TCA cycle, while knockout targets were
      found in several branch points of glycolysis. Five out of 9 tested targets led to
      an enhanced production of cytosolic human superoxide dismutase (hSOD). Expression
      of bacterial beta-glucuronidase could be enhanced as well by most of the same
      genetic modifications. Beneficial mutations were mainly related to reduction of
      the NADP/H pool and the deletion of fermentative pathways. Overexpression of the
      hSOD gene itself had a strong impact on intracellular fluxes, most of which
      changed in the same direction as predicted by the model. In vivo fluxes changed
      in the same direction as predicted to improve hSOD production. Genome scale
      metabolic modeling is shown to predict overexpression and deletion mutants which
      enhance recombinant protein production with high accuracy. 

PMID- 24853356
TI  - Use of ionic liquids as neoteric solvents in the synthesis of fused heterocycles.
AB  - Medicinal chemistry has been benefited by combinatorial chemistry and high
      throughput parallel synthesis. Ionic liquids reduce the materials and energy
      intensity of chemical processes and products, minimize or eliminate the
      dispersion of harmful chemicals in the environment, maximize the use of renewable
      resources and extend the durability and recyclability of products. It is possible
      to tune the physical and chemical properties by varying the nature of the cations
      and anions. Ionic liquids can be easily recovered, cleaned up, and reused
      repeatedly. 

PMID- 24853358
TI  - Optical properties of developing pip and stone fruit reveal underlying structural
      changes.
AB  - Analyzing the optical properties of fruits represents a powerful approach for non
      destructive observations of fruit development. With classical spectroscopy in the
      visible and near-infrared wavelength ranges, the apparent attenuation of light
      results from its absorption or scattering. In horticultural applications,
      frequently, the normalized difference vegetation index (NDVI) is employed to
      reduce the effects of varying scattering properties on the apparent signal.
      However, this simple approach appears to be limited. In the laboratory, with time
      resolved reflectance spectroscopy, the absorption coefficient, MUa , and the
      reduced scattering coefficient, MUs ', can be analyzed separately. In this study,
      these differentiated optical properties were recorded (540-940 nm), probing fruit
      tissue from the skin up to 2 cm depth in apple (Malus * domestica 'Elstar') and
      plum (Prunus domestica 'Tophit plus') harvested four times (65-145 days after
      full bloom). The MUa spectra showed typical peak at 670 nm of the chlorophyll
      absorption. The MUs ' at 670 nm in apple changed by 14.7% (18.2-15.5 cm(-1) ),
      while in plum differences of 41.5% (8.5-5.0 cm(-1) ) were found. The scattering
      power, the relative change of MUs ', was zero in apple, but enhanced in plum over
      the fruit development period. This mirrors more isotropic and constant structures
      in apple compared with plum. For horticultural applications, the larger
      variability in scattering properties of plum explains the discrepancy between
      commercially assessed NDVI values or similar indices and the absolute MUa values
      in plum (R < 0.05), while the NDVI approach appeared reasonable in apple (R >=
      0.80). 

PMID- 24853360
TI  - Drinking severity and its association with nutrition risk among African American
      women.
AB  - This analysis examined the association between drinking severity, food
      insecurity, and drinking related health comorbidities among 258 African American
      women who drank heavily from the "Sister to Sister" study. Women were stratified
      by drinking status: 23% were heavy drinkers (women who drank 30 to 52 weeks in
      the 12 months prior to study participation and consumed the equivalent of at
      least 20 alcoholic beverages at one sitting) and 77% were less heavy drinkers
      (women with all other combinations of drinking habits who drank less than 30
      weeks in the 12 months prior to study participation). Heavy drinkers were more
      likely to not check nutrition labels, skip meals to buy drugs/alcohol, and report
      a history of stomach disease, diabetes, memory, weight, and kidney problems
      compared with less heavy drinkers. The heavy drinkers were at increased nutrition
      risk due to food insecurities and were more susceptible to drinking related
      health comorbidities compared with less heavy drinkers. 

PMID- 24853361
TI  - The use of an ecodevelopmental approach to examining substance use among rural
      and urban Latino/a youth: peer, parental, and school influences.
AB  - Using an ecodevelopmental framework, we examined how peer, parent, and student
      variables influence substance (tobacco, alcohol, and marijuana) use among rural
      and urban Latino/a adolescents (N = 2,500). Generally speaking, Latino/a
      adolescents in rural areas endorsed higher levels of substance use. Among the
      primary variables of study, there were a number of nuanced differences noted
      based on location, gender, and type of substance. Peer use was related to
      individual substance use in both rural and urban areas. However, peer use was a
      significantly stronger predictor of tobacco use among rural Latinas than urban
      dwelling. Parental monitoring was not predictive of urban marijuana use, yet was
      negatively associated with substance use for all subgroups and was especially
      pronounced for female alcohol use. Parental emotional involvement predicted
      higher alcohol use among urban boys. School achievement was negatively associated
      with substance use for all subgroups while, conversely, school involvement was
      associated with higher alcohol use for rural boys. Cultural and contextual
      implications for intervention and prevention are discussed. 

PMID- 24853362
TI  - Younger versus older African Americans: patterns and prevalence of recent illicit
      drug use.
AB  - OBJECTIVES: The current study examined recent substance use among younger and
      older African Americans and factors associated with recent use. METHODS: The
      current study used a subset of African American men and women (N = 260) from the
      NEURO-HIV Epidemiological Study (Mage = 42, SD = 9.27; 59% female). Self-report
      of past 6 month substance use was evaluated for 21 different substances by routes
      of administration (ROA). RESULTS: Older adults were 1.9 times (AOR = 1.92, 95% CI
      = 1.13-3.26) more likely to have used crack in the past 6 months and half as
      likely to have used marijuana (AOR = .44, 95% CI = .25-.77). There were no
      significant differences for heroin use. DISCUSSION: Substance use at midlife may
      have significant implications for adverse social and health outcomes among
      African Americans. Findings support the need to better understand the
      developmental pathways of drug use and dependence among African Americans.

PMID- 24853363
TI  - Drinking games participation among female students at a regional Australian
      university.
AB  - Participation in drinking games (DGs) by university students is often associated
      with heavy drinking and negative social and health impacts. Although research in
      Australia indicates that university students tend to drink at risky levels, there
      is paucity of literature on DGs among students, especially those residing at
      regional universities. This research examined drinking among female college
      students of white background. Eighteen female students participated in face-to
      face in-depth interviews to describe their DG experiences. Most women played DGs
      for social and monetary reasons, with many drinking high volumes of alcohol
      during the game. Excessive drinking was linked with the type of beverage
      consumed. Despite knowing the health risks associated with DGs, there was a
      strong social imperative for these young women to play these games. Research and
      public health initiatives to better understand and address problematic drinking
      activities in rural and regional Australia have tended to ignore women and the
      dominant white populations whose heavy drinking has been largely restricted to
      private spheres. 

PMID- 24853364
TI  - Health-compromising behaviors among a multi-ethnic sample of Canadian high school
      students: risk-enhancing effects of discrimination and acculturation.
AB  - This article examines whether acculturation and experiences of discrimination
      help to explain observed ethnic disparities in rates of three health-compromising
      behaviors: interpersonal violence, drinking, and cannabis use. Data were drawn
      from a cross-sectional survey of 3,400 high school students from Toronto, Canada,
      sampled in 1998-2000. Multivariate ordinary least squares and logistic regression
      models tested for baseline differences in the health-compromising behaviors by
      ethnic identity. Subsequent models adjusted for control measures and introduced
      acculturation and discrimination measures. Results confirm that experiences of
      discrimination and acculturation are risk enhancing, whereas active cultural
      retention appears to protect ethnic youth from participation in health
      compromising activities. 

PMID- 24853365
TI  - Ethiopian origin high-risk youth: a cross-cultural examination of alcohol use,
      binge drinking, and problem behavior.
AB  - Alcohol use among underage youth has a major impact on public health, accidents,
      fatalities, and other problem behaviors. In Israel, alcohol use, binge drinking,
      and related problem behaviors are a growing concern. The purpose of this study
      was to examine underserved and underreported Ethiopian origin youth by comparing
      their substance use patterns and behavior with other high-risk youth. Data were
      collected from a purposive sample of boys of Ethiopian, former Soviet Union, and
      Israeli origin who were receiving treatment for drug use. Youth were asked to
      complete a simply worded self-report questionnaire developed for monitoring
      substance use and related problem behaviors. Ethiopian youth reported higher
      rates of family unemployment and public welfare dependence, last 30-day
      consumption of beer and hard liquor, serious fighting, and achievement decline
      when in school compared with the other youths. Findings highlight the need for
      ethno-cultural specific prevention and intervention efforts and further research
      of this high-risk, underserved group of immigrant origin youth. 

PMID- 24853366
TI  - An umbrella protocol for standardized data collection (SDC) in rectal cancer: a
      prospective uniform naming and procedure convention to support personalized
      medicine.
AB  - Predictive models allow treating physicians to deliver tailored treatment moving
      from prescription by consensus to prescription by numbers. The main features of
      an umbrella protocol for standardizing data and procedures to create a consistent
      dataset useful to obtain a trustful analysis for a Decision Support System for
      rectal cancer are reported. 

PMID- 24853367
TI  - Correlation of contouring variation with modeled outcome for conformal non-small
      cell lung cancer radiotherapy.
AB  - BACKGROUND AND PURPOSE: Contouring variation is a well know uncertainty in modern
      radiotherapy. This study investigates the relationship between contouring
      variation, tumor control probability (TCP) and equivalent uniform dose (EUD) for
      conformal non-small cell lung cancer (NSCLC) radiotherapy. MATERIAL AND METHODS:
      Seven patients were retrospectively recruited to the study and multiple PTV
      contours were generated based on CT and PET imaging by three observers. Plans
      were created for each PTV volume. Volumes were analyzed geometrically using
      volume, location, dimension and conformity index (CI). Radiobiological plan
      analysis consisted of two TCP models and EUD. Spearman's correlation coefficient
      (rho) was used to quantify the association between geometric variation and
      radiobiological metrics. RESULTS: The variation in CI and TCP for the study was
      0.66-0.90% and 0.19-0.68%. Changes in lateral dimension and volume were
      significantly correlated with TCP and EUD with an average rho of -0.49 and 0.43
      (p<0.01) respectively. CONCLUSIONS: TCP and geometric contour variation show
      significant correlation. This correlation was most significant for changes in
      lateral dimensions of PTV volumes. This association may be used in the assessment
      of contouring protocol violations in multicenter clinical trials and aid in the
      design of future contouring studies.

PMID- 24853370
TI  - A novel method for direct measurement of complement convertases activity in human
      serum.
AB  - Complement convertases are enzymatic complexes that play a central role in
      sustaining and amplification of the complement cascade. Impairment of complement
      function leads directly or indirectly to pathological conditions, including
      higher infection rate, kidney diseases, autoimmune- or neurodegenerative diseases
      and ischaemia-reperfusion injury. An assay for direct measurement of activity of
      the convertases in patient sera is not available. Existing assays testing
      convertase function are based on purified complement components and, thus,
      convertase formation occurs under non-physiological conditions. We designed a new
      assay, in which C5 blocking compounds enabled separation of the complement
      cascade into two phases: the first ending at the stage of C5 convertases and the
      second ending with membrane attack complex formation. The use of rabbit
      erythrocytes or antibody-sensitized sheep erythrocytes as the platforms for
      convertase formation enabled easy readout based on measurement of haemolysis.
      Thus, properties of patient sera could be studied directly regarding convertase
      activity and membrane attack complex formation. Another advantage of this assay
      was the possibility to screen for host factors such as C3 nephritic factor and
      other anti-complement autoantibodies, or gain-of-function mutations, which
      prolong the half-life of complement convertases. Herein, we present proof of
      concept, detailed description and validation of this novel assay.

PMID- 24853369
TI  - The effects of a novel hormonal breast cancer therapy, endoxifen, on the mouse
      skeleton.
AB  - Endoxifen has recently been identified as the predominant active metabolite of
      tamoxifen and is currently being developed as a novel hormonal therapy for the
      treatment of endocrine sensitive breast cancer. Based on past studies in breast
      cancer cells and model systems, endoxifen classically functions as an anti
      estrogenic compound. Since estrogen and estrogen receptors play critical roles in
      mediating bone homeostasis, and endoxifen is currently being implemented as a
      novel breast cancer therapy, we sought to comprehensively characterize the in
      vivo effects of endoxifen on the mouse skeleton. Two month old ovariectomized
      C57BL/6 mice were treated with vehicle or 50 mg/kg/day endoxifen hydrochloride
      via oral gavage for 45 days. Animals were analyzed by dual-energy x-ray
      absorptiometry, peripheral quantitative computed tomography, micro-computed
      tomography and histomorphometry. Serum from control and endoxifen treated mice
      was evaluated for bone resorption and bone formation markers. Gene expression
      changes were monitored in osteoblasts, osteoclasts and the cortical shells of
      long bones from endoxifen treated mice and in a human fetal osteoblast cell line.
      Endoxifen treatment led to significantly higher bone mineral density and bone
      mineral content throughout the skeleton relative to control animals. Endoxifen
      treatment also resulted in increased numbers of osteoblasts and osteoclasts per
      tissue area, which was corroborated by increased serum levels of bone formation
      and resorption markers. Finally, endoxifen induced the expression of osteoblast,
      osteoclast and osteocyte marker genes. These studies are the first to examine the
      in vivo and in vitro impacts of endoxifen on bone and our results demonstrate
      that endoxifen increases cancellous as well as cortical bone mass in
      ovariectomized mice, effects that may have implications for postmenopausal breast
      cancer patients. 

PMID- 24853372
TI  - Umbelliferone increases the expression of adipocyte-specific genes in 3T3-L1
      adipocyte.
AB  - Umbelliferone (UMB), a natural product of coumarin family, has been shown to
      reduce blood glucose and to improve lipid profiles in streptozotocin (STZ)
      induced diabetic rats. Our objective was to examine the effect of UMB on
      adipogenesis by investigating its stimulatory effect on lipid accumulation and
      mRNA expression of adipogenic transcription factors and adipocyte-specific genes
      in 3 T3-L1 preadipocyte culture. An Oil Red O staining was used to monitor lipid
      accumulation, and we found that UMB treatment at concentration range of 10-100
      MUM significantly increased lipid accumulation of differentiating 3 T3-L1 cells.
      At the molecular level of adipogenesis, we examined the mRNA expression of
      adipogenic transcription factors, peroxisome proliferator-activated receptor
      gamma, CCAAT/enhancer-binding protein alpha, and sterol regulatory element
      binding protein 1c. Those transcription factors were increased by UMB at 10-100
      MUM. Interestingly, UMB also stimulated the mRNA expression of adipocyte-specific
      genes, adipocyte fatty acid-binding protein, lipoprotein lipase, fatty acid
      synthase, fatty acid translocase, and adiponectin. Our findings indicate that the
      stimulatory effect of UMB on adipocyte differentiation likely occurs through up
      regulation of adipogenic transcription factors and downstream adipocyte-specific
      gene expression.

PMID- 24853371
TI  - Serological responses and biomarker evaluation in mice and pigs exposed to tsetse
      fly bites.
AB  - BACKGROUND: Tsetse flies are obligate blood-feeding insects that transmit African
      trypanosomes responsible for human sleeping sickness and nagana in livestock. The
      tsetse salivary proteome contains a highly immunogenic family of the endonuclease
      like Tsal proteins. In this study, a recombinant version of Tsal1 (rTsal1) was
      evaluated in an indirect ELISA to quantify the contact with total Glossina
      morsitans morsitans saliva, and thus the tsetse fly bite exposure.
      METHODOLOGY/PRINCIPAL FINDINGS: Mice and pigs were experimentally exposed to
      different G. m. morsitans exposure regimens, followed by a long-term follow-up of
      the specific antibody responses against total tsetse fly saliva and rTsal1. In
      mice, a single tsetse fly bite was sufficient to induce detectable IgG antibody
      responses with an estimated half-life of 36-40 days. Specific antibody responses
      could be detected for more than a year after initial exposure, and a single bite
      was sufficient to boost anti-saliva immunity. Also, plasmas collected from tsetse
      exposed pigs displayed increased anti-rTsal1 and anti-saliva IgG levels that
      correlated with the exposure intensity. A strong correlation between the
      detection of anti-rTsal1 and anti-saliva responses was recorded. The ELISA test
      performance and intra-laboratory repeatability was adequate in the two tested
      animal models. Cross-reactivity of the mouse IgGs induced by exposure to
      different Glossina species (G. m. morsitans, G. pallidipes, G. palpalis
      gambiensis and G. fuscipes) and other hematophagous insects (Stomoxys calcitrans
      and Tabanus yao) was evaluated. CONCLUSION: This study illustrates the potential
      use of rTsal1 from G. m. morsitans as a sensitive biomarker of exposure to a
      broad range of Glossina species. We propose that the detection of anti-rTsal1
      IgGs could be a promising serological indicator of tsetse fly presence that will
      be a valuable tool to monitor the impact of tsetse control efforts on the African
      continent.

PMID- 24853373
TI  - Spatial generalization in operant learning: lessons from professional basketball.
AB  - In operant learning, behaviors are reinforced or inhibited in response to the
      consequences of similar actions taken in the past. However, because in natural
      environments the "same" situation never recurs, it is essential for the learner
      to decide what "similar" is so that he can generalize from experience in one
      state of the world to future actions in different states of the world. The
      computational principles underlying this generalization are poorly understood, in
      particular because natural environments are typically too complex to study
      quantitatively. In this paper we study the principles underlying generalization
      in operant learning of professional basketball players. In particular, we utilize
      detailed information about the spatial organization of shot locations to study
      how players adapt their attacking strategy in real time according to recent
      events in the game. To quantify this learning, we study how a make?miss from one
      location in the court affects the probabilities of shooting from different
      locations. We show that generalization is not a spatially-local process, nor is
      governed by the difficulty of the shot. Rather, to a first approximation, players
      use a simplified binary representation of the court into 2 pt and 3 pt zones.
      This result indicates that rather than using low-level features, generalization
      is determined by high-level cognitive processes that incorporate the abstract
      rules of the game.

PMID- 24853374
TI  - Meeting Swedish Health Care System: Immigrant Parents of Children With Asthma
      Narrate.
AB  - Coming to a new country involves many challenges. One of them is to approach a
      new health care system when you have a child with asthma. The aim of this study
      was to gain a broader understanding of immigrant parents' experiences of the
      Swedish health care system. Twelve parents of children with asthma were
      interviewed and their narratives were analyzed by using qualitative content
      analysis. The results show that immigrant parents' experiences of Swedish health
      care vary and involve both advantages and disadvantages. Advantages of the
      Swedish health care system are described as Being met with respect and Affordable
      care, while disadvantages are described as Problems with communication, Being
      discriminated against and Lack of confidence. The disadvantages are challenges
      for health care professionals, who are expected to offer care on equal terms to
      the whole population. Therefore, they need to provide culturally competent care
      and encourage immigrant parents to voice their expectations and worries. 

PMID- 24853375
TI  - Evaluation of different cooking conditions on broccoli (Brassica oleracea var.
      italica) to improve the nutritional value and consumer acceptance.
AB  - The objective of this study was to gain insights into the effect of the cooking
      method on the liking as well as the retention of glucosinolates in broccoli. With
      this knowledge it can be concluded whether the health aspects of broccoli be
      improved by the cooking method without deteriorating sensory perception. For
      this, broccoli was cooked by methods commonly applied by consumers: boiling with
      a cold (water) start; boiling with a hot (water) start; and steaming. Firmness,
      greenness and amount of total glucosinolates in cooked broccoli were
      instrumentally determined. Sensory evaluation by untrained consumers (n = 99) for
      liking and sensory attributes intensity rating were performed on broccoli cooked
      by steaming and boiling-cold start at three time points, which resulted in
      'high', 'medium', 'low' firm broccoli samples. At the end of cooking, steaming
      showed an increase in the amount of total glucosinolates (+17%). Boiling-hot
      start (-41%) and boiling-cold start (-50%) showed a decrease in amount of total
      glucosinolates. Sensory evaluation did not show statistically significant
      differences between steaming and boiling-cold start in liking at 'high' and
      'medium' firmness; and in the attribute intensity ratings (except for juiciness
      at 'medium' firmness, and flavour at 'medium' and 'low' firmness). This study
      demonstrates that medium firm broccoli showed optimum liking and that steaming
      compared to boiled-cold start showed higher amount of glucosinolates. It is
      concluded that the health aspects of broccoli can be improved without reducing
      the sensory aspects by optimising the cooking method.

PMID- 24853377
TI  - Labelling and tracking of human mesenchymal stromal cells in preclinical studies
      and large animal models of degenerative diseases.
AB  - Success of stem cell therapies were reported in different medical disciplines,
      including haematology, rheumatology, orthopaedic surgery, traumatology, and
      others. Currently, more than 4000 clinical trials using stem cells have been
      completed or are underway, among which 378 investigated or are at present
      investigating mesenchymal stromal cells (MSCs). The majority of clinical trials
      using stem- or progenitor- cells, including hematopoietic stem cells and MSCs,
      target the immune system. However, therapies based on MSCs are increasingly
      implemented to treat symptoms in which failure of the resident stem cells in
      situ, or malfunction of tissues or structures are not associated with immune
      cells or inflammation, but instead are associated with mechanical or metabolic
      stress, ageing, developmental or acquired malformations, and other causes. To
      proceed further in the development of stem cell therapies as a safe and effective
      treatment for surgical and other medical specialities, the behaviour of MSCs
      implanted in preclinical models and their impact on the site of application need
      to be explored in detail. Depending on the pre-clinical model employed, tracking
      of labelled stem cells in live animals makes an enormous difference for
      exploration of the mechanisms and kinetics involved in MSC-mediated tissue
      regeneration. Here we review (pre-)clinically applicable key methods to label
      human MSCs for short and long-term observations in small and large animal models.

PMID- 24853376
TI  - Chronic electrical stimulation with a suprachoroidal retinal prosthesis: a
      preclinical safety and efficacy study.
AB  - PURPOSE: To assess the safety and efficacy of chronic electrical stimulation of
      the retina with a suprachoroidal visual prosthesis. METHODS: Seven normally
      sighted feline subjects were implanted for 96-143 days with a suprachoroidal
      electrode array and six were chronically stimulated for 70-105 days at levels
      that activated the visual cortex. Charge balanced, biphasic, current pulses were
      delivered to platinum electrodes in a monopolar stimulation mode. Retinal
      integrity/function and the mechanical stability of the implant were assessed
      monthly using electroretinography (ERG), optical coherence tomography (OCT) and
      fundus photography. Electrode impedances were measured weekly and electrically
      evoked visual cortex potentials (eEVCPs) were measured monthly to verify that
      chronic stimuli were suprathreshold. At the end of the chronic stimulation
      period, thresholds were confirmed with multi-unit recordings from the visual
      cortex. Randomized, blinded histological assessments were performed by two
      pathologists to compare the stimulated and non-stimulated retina and adjacent
      tissue. RESULTS: All subjects tolerated the surgical and stimulation procedure
      with no evidence of discomfort or unexpected adverse outcomes. After an initial
      post-operative settling period, electrode arrays were mechanically stable. Mean
      electrode impedances were stable between 11-15 kOmega during the implantation
      period. Visually-evoked ERGs & OCT were normal, and mean eEVCP thresholds did not
      substantially differ over time. In 81 of 84 electrode-adjacent tissue samples
      examined, there were no discernible histopathological differences between
      stimulated and unstimulated tissue. In the remaining three tissue samples there
      were minor focal fibroblastic and acute inflammatory responses. CONCLUSIONS:
      Chronic suprathreshold electrical stimulation of the retina using a
      suprachoroidal electrode array evoked a minimal tissue response and no adverse
      clinical or histological findings. Moreover, thresholds and electrode impedance
      remained stable for stimulation durations of up to 15 weeks. This study has
      demonstrated the safety and efficacy of suprachoroidal stimulation with charge
      balanced stimulus currents.

PMID- 24853378
TI  - Arrangement of the Clostridium baratii F7 toxin gene cluster with identification
      of a sigma factor that recognizes the botulinum toxin gene cluster promoters.
AB  - Botulinum neurotoxin (BoNT) is the most poisonous substances known and its eight
      toxin types (A to H) are distinguished by the inability of polyclonal antibodies
      that neutralize one toxin type to neutralize any of the other seven toxin types.
      Infant botulism, an intestinal toxemia orphan disease, is the most common form of
      human botulism in the United States. It results from swallowed spores of
      Clostridium botulinum (or rarely, neurotoxigenic Clostridium butyricum or
      Clostridium baratii) that germinate and temporarily colonize the lumen of the
      large intestine, where, as vegetative cells, they produce botulinum toxin.
      Botulinum neurotoxin is encoded by the bont gene that is part of a toxin gene
      cluster that includes several accessory genes. We sequenced for the first time
      the complete botulinum neurotoxin gene cluster of nonproteolytic C. baratii type
      F7. Like the type E and the nonproteolytic type F6 botulinum toxin gene clusters,
      the C. baratii type F7 had an orfX toxin gene cluster that lacked the regulatory
      botR gene which is found in proteolytic C. botulinum strains and codes for an
      alternative sigma factor. In the absence of botR, we identified a putative
      alternative regulatory gene located upstream of the C. baratii type F7 toxin gene
      cluster. This putative regulatory gene codes for a predicted sigma factor that
      contains DNA-binding-domain homologues to the DNA-binding domains both of BotR
      and of other members of the TcdR-related group 5 of the sigma70 family that are
      involved in the regulation of toxin gene expression in clostridia. We showed that
      this TcdR-related protein in association with RNA polymerase core enzyme
      specifically binds to the C. baratii type F7 botulinum toxin gene cluster
      promoters. This TcdR-related protein may therefore be involved in regulating the
      expression of the genes of the botulinum toxin gene cluster in neurotoxigenic C.
      baratii. 

PMID- 24853379
TI  - An easy-to-hard effect after nonreinforced preexposure in a sweetness
      discrimination.
AB  - Experiments 1A and 1B used a taste-aversion procedure with rats to demonstrate
      that exposure to easily discriminated flavors along a dimension (1 % and 10 %
      sucrose) can facilitate learning a subsequent hard discrimination (4 % and 7 %
      sucrose) when one of those flavors is paired with illness. Experiment 1A compared
      the effects of preexposure to the easily discriminated flavors against exposure
      to the same stimuli used in the discrimination training or no exposure at all.
      Experiment 1B replicated the conditions in Experiment 1A, with 2 additional days
      of training and unrestricted access to the flavors on CS+/CS- trials in
      discrimination training. Contrary to findings with multidimensional stimuli
      (Scahill & Mackintosh, Journal of Experimental Psychology: Animal Behavior
      Processes, 30, 96-103, 2004; Suret & McLaren, The Quarterly Journal of
      Experimental Psychology, 56B, 30-42, 2003), we found that preexposure to the
      easily discriminable stimuli varying along a single dimension of sweetness
      facilitated subsequent discrimination training over the other conditions in each
      experiment. We discuss the results in terms of the ideas presented by Gibson
      (1969) and Mackintosh (Psychological Review, 82, 276-298, 1975) and in terms of
      hedonic variables not considered by theories of perceptual learning.

PMID- 24853380
TI  - Overactivated neddylation pathway as a therapeutic target in lung cancer.
AB  - BACKGROUND: A number of oncoproteins and tumor suppressors are known to be
      neddylated, but whether the neddylation pathway is entirely activated in human
      cancer remains unexplored. METHODS: NEDD8-activating enzyme (NAE) (E1) and NEDD8
      conjugating enzyme (E2) expression and global-protein neddylation were examined
      by immunohistochemistry, immunoblotting, and real-time polymerase chain reaction
      analysis. Cell proliferation, clonogenic survival, migration, and motility in
      vitro, as well as tumor formation and metastasis in vivo, were determined upon
      neddylation inhibition by MLN4924, an investigational NEDD8-activating enzyme
      inhibitor. Survival was analyzed with Kaplan-Meier methods and compared by the
      log-rank test. All statistical tests were two-sided. RESULTS: The entire
      neddylation pathway, including NEDD8-activating enzyme E1, NEDD8-conjugating
      enzyme E2, and global-protein neddylation, is overactivated in both lung
      adenocarcinoma and squamous-cell carcinoma. Compared with lung adenocarcinoma
      patients with low expression, those with high expression had worse overall
      survival (NEDD8-activating enzyme E1 subunit 1 [NAE1]: hazard ratio [HR] = 2.07,
      95% confidence interval [CI] = 0.95 to 4.52, P = .07; ubiquitin-conjugating
      enzyme E2M (UBC12): HR = 13.26, 95% CI = 1.77 to 99.35, P = .01; global protein
      neddylation: HR = 3.74, 95% CI = 1.65 to 8.47, P = .002). Moreover, inhibition of
      neddylation by the NAE inhibitor MLN4924 statistically significantly suppressed
      proliferation, survival, migration, and motility of lung cancer cells in vitro
      and tumor formation and metastasis in vivo. At the molecular level, MLN4924
      inactivated Cullin-RING E3 ligases, led to accumulation of tumor-suppressive
      Cullin-RING E3 ligase substrates and induced phorbol-12-myristate-13-acetate
      induced protein 1 (NOXA)-dependent apoptosis or cellular senescence. CONCLUSIONS:
      Our study highlights the overactivated neddylation pathway in lung cancer
      development and as a promising therapeutic target.

PMID- 24853381
TI  - Fludarabine, cyclophosphamide and rituximab as first-line treatment in patients
      with newly diagnosed follicular lymphoma.
AB  - Fludarabine-based regimens are highly effective as first-line therapy in patients
      with follicular lymphoma. Nevertheless, noticeable haematological toxicity has
      been reported using fludarabine-based regimens. AIM: To analyse the combination
      of low-dose oral fludarabine and cyclophosphamide plus rituximab (FCR) as
      induction therapy, followed by rituximab as maintenance therapy. METHODS: We
      retrospectively analysed 73 patients diagnosed with low-grade follicular lymphoma
      treated with two different schemes: attenuated oral (AO) and standard intravenous
      (SIV) FCR. RESULTS: Overall response rate (ORR) was 95% (complete response rate,
      CRR 79.5%, partial response, PR 15.4%). CRR was 84.6% in AO vs. 61.9% in SIV (P =
      0.058). 44.4% of patients underwent maintenance therapy. Grade 3-4 toxicities
      included neutropenia: 65.4%; anaemia: 39.7%; thrombocytopenia: five patients;
      infectious complications: six patients. There were no treatment-related deaths.
      6.8% had a secondary malignancy. Progression-free survival (PFS) was 84.6% at 12
      yr. The following variables influenced PFS in multivariate analysis: Hb < 12 g/dL
      [HR 4.7 (95% CI 1.18-18.6)], response after induction [HR 4.9 (95% CI 1.01-24)]
      for PR vs. CR and [HR 21.27 (95% CI 4.33-104)] for SD/DP vs. CR. OS was 83.1% at
      12 yr. The following variables significantly influenced OS in multivariate
      analysis: not receiving rituximab as maintenance therapy (HR 10.7 (95% CI 1.4
      82.5), increased levels of beta2-microglobulin [HR 5.2 (95% CI 1.16-23.7)].
      CONCLUSIONS: FCR allowed us to obtain a high response rate, which translated into
      promising progression free and overall survival with an acceptable and manageable
      toxicity profile, especially with the attenuated oral scheme.

PMID- 24853383
TI  - Ultrafast molecule separation through layered WS(2) nanosheet membranes.
AB  - Two-dimensional layered materials have joined in the family of size-selective
      separation membranes recently. Here, chemically exfoliated tungsten disulfide
      (WS2) nanosheets are assembled into lamellar thin films and explored as an
      ultrafast separation membrane for small molecules with size of about 3 nm.
      Layered WS2 membranes exhibit 5- and 2-fold enhancement in water permeance of
      graphene oxide membranes and MoS2 laminar membranes with similar rejection,
      respectively. To further increase the water permeance, ultrathin nanostrands are
      used as templates to generate more fluidic channel networks in the WS2 membrane.
      The water permeation behavior and separation performance in the pressure loading
      unloading process reveal that the channels created by the ultrathin nanostrands
      are cracked under high pressure and result in a further 2-fold increase of the
      flux without significantly degrading the rejection for 3 nm molecules. This is
      supported by finite-element-based mechanical simulation. These layered WS2
      membranes demonstrate up to 2 orders of magnitude higher separation performance
      than that of commercial membranes with similar rejections and hold the promising
      potential for water purification. 

PMID- 24853382
TI  - Increased fluid administration in the first three hours of sepsis resuscitation
      is associated with reduced mortality: a retrospective cohort study.
AB  - BACKGROUND: The surviving sepsis guidelines recommend early aggressive fluid
      resuscitation within 6 h of sepsis onset. Although rapid fluid administration may
      offer benefit, studies on the timing of resuscitation are lacking. We
      hypothesized that there is an association between quicker, adequate fluid
      resuscitation and patient outcome from sepsis onset time. METHODS: This is a
      retrospective cohort study of consecutive adults with severe sepsis and septic
      shock admitted to a quaternary care medical ICU between January 2007 and December
      2009. Data were collected from a previously validated electronic medical
      database. Multivariate regression modeling was performed, adjusting for age,
      admission weight, Sequential Organ Failure Assessment score, APACHE (Acute
      Physiology and Chronic Health Examination) III score, and total fluid
      administration within the first 6 h of sepsis onset time. RESULTS: Of 651
      patients with severe sepsis and septic shock screened, 594 had detailed fluid
      data. In a univariate analysis, the median amount of fluid within the first 3 h
      for survivors at discharge was 2,085 mL (940-4,080 mL) and for nonsurvivors,
      1,600 mL (600-3,010 mL; P = .007). In comparison, during the latter 3 h, the
      median amount was 660 mL (290-1,485 mL) vs 800 mL (360-1,680 mL; P = .09),
      respectively. After adjusting for confounders, the higher proportion of total
      fluid received within the first 3 h was associated with decreased hospital
      mortality (OR, 0.34; 95% CI, 0.15-0.75; P = .008). CONCLUSIONS: Earlier fluid
      resuscitation (within the first 3 h) is associated with a greater number of
      survivors with severe sepsis and septic shock.

PMID- 24853385
TI  - Adipose-derived regenerative cell therapy inhibits the progression of
      monocrotaline-induced pulmonary hypertension in rats.
AB  - AIMS: Functional and structural changes in pulmonary vasculature characterize
      pulmonary arterial hypertension (PAH) and the prognosis of advanced PAH remains
      poor despite progress in pharmacotherapy. Adipose-derived regenerative cells
      (ADRCs) promote cell regeneration at pathological sites and comprise a novel
      therapy for ailments of various organs. We investigated the effects of ADRC
      therapy in rat models of monocrotaline (MCT)-induced pulmonary hypertension (PH)
      and the underlying mechanisms. MAIN METHODS: Rats were assigned to Control and
      MCT groups without and with (M/A) intravenous transfusion of seven million ADRCs
      on day 7. We echocardiographically evaluated pulmonary hypertension as pulmonary
      artery flow acceleration time (PAAT) and deceleration (PADc). Right ventricular
      (RV) systolic pressure was measured by catheterization on day 28 and then
      pathological changes in pulmonary vessels were assessed. We analyzed PAH
      associated gene expression on day 14 using real-time RT-PCR. KEY FINDINGS:
      Echocardiography and RV catheterization showed that ADRC therapy inhibited PH
      development (assessed as PAAT, PADc, and RV systolic pressure) at day 28 (MCT vs.
      M/A, P<0.05). Pulmonary vascular remodeling was also inhibited (vessel wall
      thickness: MCT vs. M/A, P<0.01). Messenger RNA levels of endothelin (ET) A and B
      receptors, ET-1 and transforming growth factor (TGF)-beta increased in the lungs
      by MCT were suppressed by ADRCs (MCT vs. M/A, P<0.05). SIGNIFICANCE: The
      development of PH was inhibited by ADRCs through suppressing changes in the
      expression of genes associated with ET and TGF-beta systems. We believe that ADRC
      therapy could serve as a novel strategy for treating PH.

PMID- 24853384
TI  - Subtype-dependent prognostic relevance of an interferon-induced pathway metagene
      in node-negative breast cancer.
AB  - The majority of gene expression signatures developed to predict the likelihood to
      relapse in breast cancer (BC) patients assigns a high risk score to patients with
      Estrogen Receptor (ER) negative or highly proliferating tumors. We aimed to
      identify a signature of differentially expressed (DE) metagenes, rather than
      single DE genes, associated with distant metastases beyond classical risk
      factors. We used 105 gene expression profiles from consecutive BCs to identify
      metagenes whose prognostic role was defined on an independent series of 92
      ESR1+/ERBB2- node-negative BCs (42 cases developing metastases within 5 years
      from diagnosis and 50 cases metastasis-free for more than 5 years, comparable for
      age, tumor size, ER status and surgery). Findings were validated on publicly
      available datasets of 684 node-negative BCs including all the subtypes. Only a
      metagene containing interferon-induced genes (IFN metagene) proved to be
      predictive of distant metastasis in our series of patients with ESR1+/ERBB2-
      tumors (P = 0.029), and such a finding was validated on 457 ESR1+/ERBB2- BCs from
      public datasets (P = 0.0424). Conversely, the IFN metagene was associated with a
      low risk of metastasis in 104 ERBB2+ tumors (P = 0.0099) whereas it did not prove
      to significantly affect prognosis in 123 ESR1-/ERBB2- tumors (P = 0.2235). A
      complex prognostic interaction was revealed in ESR1+/ERBB2- and ERBB2+ tumors
      when the association between the IFN metagene and a T-cell metagene was
      considered. The study confirms the importance of analyzing prognostic variables
      separately within BC subtypes, highlights the advantages of using metagenes
      rather than genes, and finally identifies in node-negative ESR1+/ERBB2- BCs, the
      unfavorable role of high IFN metagene expression.

PMID- 24853386
TI  - Unexpected and novel functions of complement proteins.

PMID- 24853389
TI  - ALK-positive non-small cell lung cancer: mechanisms of resistance and emerging
      treatment options.
AB  - Targeted therapy has emerged as an effective treatment option for certain
      molecular subsets of advanced stage non-small cell lung cancer (NSCLC). The
      discovery of the echinoderm microtubule-associated protein like 4-anaplastic
      lymphoma kinase (EML4-ALK) translocation as an oncogenic driver has led to the
      development of novel therapies with activity in vitro and in the clinic. The
      first-in-class tyrosine kinase inhibitor crizotinib is effective against ALK
      positive NSCLC and is currently used as first-line or salvage therapy in the
      setting of advanced disease. However, resistance inevitably develops through a
      variety of mechanisms, including point mutations affecting the fusion protein,
      activation of bypass signaling pathways, copy number gain of ALK, and other
      means. Increased understanding of these pathways is essential for tailoring
      treatment choices to improve outcomes and minimize toxicities. Potent second
      generation ALK inhibitors currently in trials are producing encouraging results
      in ALK-positive NSCLC, even in patients with acquired resistance to crizotinib.
      The success in identifying the ALK translocations and rapidly developing targeted
      drugs to exploit it paves the way for a better understanding of NSCLC biology and
      the quest to provide effective, personalized treatment for lung cancer patients.

PMID- 24853388
TI  - Preference for distinct functional conformations of the dopamine transporter
      alters the relationship between subjective effects of cocaine and stimulation of
      mesolimbic dopamine.
AB  - BACKGROUND: Subjective effects of cocaine are mediated primarily by dopamine (DA)
      transporter (DAT) blockade. The present study assessed the hypothesis that
      different DAT conformational equilibria regulate differences in cocaine-like
      subjective effects and extracellular DA induced by diverse DA-uptake inhibitors
      (DUIs). METHODS: The relationship between cocaine-like subjective effects and
      stimulation of mesolimbic DA levels by standard DUIs (cocaine, methylphenidate,
      WIN35,428) and atypical DUIs (benztropine analogs: AHN1-055, AHN2-005, JHW007)
      was investigated using cocaine discrimination and DA microdialysis procedures in
      rats. RESULTS: All drugs stimulated DA levels with different maxima and time
      courses. Standard DUIs, which preferentially bind outward-facing DAT
      conformations, fully substituted for cocaine, consistently producing cocaine-like
      subjective effects at DA levels of 100-125% over basal values, regardless of dose
      or pretreatment time. The atypical DUIs, with DAT binding minimally affected by
      DAT conformation, produced inconsistent cocaine-like subjective effects. Full
      effects were obtained, if at all, only at a few doses and pretreatment times and
      at DA levels 600-700% greater than basal values. Importantly, the linear, time
      independent, relationship between cocaine-like subjective effects and DA
      stimulation obtained with standard DUIs was not obtained with the atypical DUIs.
      CONCLUSIONS: These results suggest a time-related desensitization process
      underlying the reduced cocaine subjective effects of atypical DUIs that may be
      differentially induced by the binding modalities identified using molecular
      approaches. Since the DAT is the target of several drugs for treating
      neuropsychiatric disorders, such as attention-deficit/hyperactivity disorder,
      these results help to identify safe and effective medications with minimal
      cocaine-like subjective effects that contribute to abuse liability.

PMID- 24853390
TI  - Eukaryotic elongation factor 2 kinase, an unusual enzyme with multiple roles.
AB  - Eukaryotic elongation factor 2 kinase (eEF2K) is a member of the small group of
      atypical 'alpha-kinases'. It phosphorylates and inhibits eukaryotic elongation
      factor 2, to slow down the elongation stage of protein synthesis, which normally
      consumes a great deal of energy and amino acids. The activity of eEF2K is
      normally dependent on calcium ions and calmodulin. eEF2K is also regulated by a
      plethora of other inputs, including inhibition by signalling downstream of
      anabolic signalling pathways such as the mammalian target of rapamycin complex 1.
      Recent data show that eEF2K helps to protect cancer cells against nutrient
      starvation and is also cytoprotective in other settings, including hypoxia.
      Growing evidence points to roles for eEF2K in neurological processes such as
      learning and memory and perhaps in depression. 

PMID- 24853387
TI  - Chronic cannabinoid receptor 2 activation reverses paclitaxel neuropathy without
      tolerance or cannabinoid receptor 1-dependent withdrawal.
AB  - BACKGROUND: Mixed cannabinoid receptor 1 and 2 (CB1 and CB2) agonists such as
      Delta(9)-tetrahydrocannabinol (Delta(9)-THC) can produce tolerance, physical
      withdrawal, and unwanted CB1-mediated central nervous system side effects.
      Whether repeated systemic administration of a CB2-preferring agonist engages CB1
      receptors or produces CB1-mediated side effects is unknown. METHODS: We evaluated
      antiallodynic efficacy, possible tolerance, and cannabimimetic side effects of
      repeated dosing with a CB2-preferring agonist AM1710 in a model of chemotherapy
      induced neuropathy produced by paclitaxel using CB1 knockout (CB1KO), CB2
      knockout (CB2KO), and wild-type (WT) mice. Comparisons were made with the
      prototypic classic cannabinoid Delta(9)-THC. We also explored the site and
      possible mechanism of action of AM1710. RESULTS: Paclitaxel-induced mechanical
      and cold allodynia developed to an equivalent degree in CB1KO, CB2KO, and WT
      mice. Both AM1710 and Delta(9)-THC suppressed established paclitaxel-induced
      allodynia in WT mice. In contrast to Delta(9)-THC, chronic administration of
      AM1710 did not engage CB1 activity or produce antinociceptive tolerance, CB1
      mediated cannabinoid withdrawal, hypothermia, or motor dysfunction. Antiallodynic
      efficacy of systemic administration of AM1710 was absent in CB2KO mice and WT
      mice receiving the CB2 antagonist AM630, administered either systemically or
      intrathecally. Intrathecal administration of AM1710 also attenuated paclitaxel
      induced allodynia in WT mice, but not CB2KO mice, implicating a possible role for
      spinal CB2 receptors in AM1710 antiallodynic efficacy. Finally, both acute and
      chronic administration of AM1710 decreased messenger RNA levels of tumor necrosis
      factor-alpha and monocyte chemoattractant protein 1 in lumbar spinal cord of
      paclitaxel-treated WT mice. CONCLUSIONS: Our results highlight the potential of
      prolonged use of CB2 agonists for managing chemotherapy-induced allodynia with a
      favorable therapeutic ratio marked by sustained efficacy and absence of
      tolerance, physical withdrawal, or CB1-mediated side effects.

PMID- 24853391
TI  - Designing a community engagement framework for a new dengue control method: a
      case study from central Vietnam.
AB  - BACKGROUND: The Wolbachia strategy aims to manipulate mosquito populations to
      make them incapable of transmitting dengue viruses between people. To test its
      efficacy, this strategy requires field trials. Public consultation and engagement
      are recognized as critical to the future success of these programs, but questions
      remain regarding how to proceed. This paper reports on a case study where social
      research was used to design a community engagement framework for a new dengue
      control method, at a potential release site in central Vietnam.
      METHODOLOGY/PRINCIPAL FINDINGS: The approach described here, draws on an
      anthropological methodology and uses both qualitative and quantitative methods to
      design an engagement framework tailored to the concerns, expectations, and socio
      political setting of a potential trial release site for Wolbachia-infected Aedes
      aegypti mosquitoes. The process, research activities, key findings and how these
      were responded to are described. Safety of the method to humans and the
      environment was the most common and significant concern, followed by efficacy and
      impact on local lives. Residents expected to be fully informed and engaged about
      the science, the project, its safety, the release and who would be responsible
      should something go wrong. They desired a level of engagement that included
      regular updates and authorization from government and at least one member of
      every household at the release site. CONCLUSIONS/SIGNIFICANCE: Results
      demonstrate that social research can provide important and reliable insights into
      public concerns and expectations at a potential release site, as well as guidance
      on how these might be addressed. Findings support the argument that using
      research to develop more targeted, engagement frameworks can lead to more
      sensitive, thorough, culturally comprehensible and therefore ethical consultation
      processes. This approach has now been used successfully to seek public input and
      eventually support for releases Wolbachia-infected mosquitoes, in two different
      international settings--Australia and Vietnam.

PMID- 24853392
TI  - Evolution of adaptive immunity: implications of a third lymphocyte lineage in
      lampreys.
AB  - An alternative antigen receptor, named the variable lymphocyte receptor (VLR),
      was first identified in lampreys in 2004. Since then, the mechanism of VLR
      diversification via somatic gene assembly and the function of VLR-expressing
      lymphocytes have been the subject of much research. VLRs comprise leucine-rich
      repeat (LRR) motifs and are found only in the most phylogenetically distant
      vertebrates from mammals, lampreys, and hagfish. Previous reports showed that
      VLRA and VLRB are reciprocally expressed by lymphocytes that resemble T- and B
      cells; however, more recent reports show that another VLR, VLRC, is expressed on
      a third lymphocyte lineage, which may be equivalent to gammadelta T cells. The
      existence of three major lymphocyte lineages - one B-cell-like and two T-cell
      like - and their development in lampreys, parallels the mammalian adaptive immune
      system. This suggests that these three cell lineages were present in the common
      vertebrate ancestor approximately 500 million years ago. 

PMID- 24853394
TI  - Evaluation of amino acid ester-based ionic liquids as buffer additives in CE for
      the separation of 2-arylpropionic acids nonsteroidal anti-inflammatory drugs.
AB  - The aim of the present study is the CE performance evaluation for the separation
      of 2-arylpropionic acid nonsteroidal anti-inflammatory drugs. In particular, the
      separation of indoprofen, carprofen, ketoprofen, ibuprofen, and flurbiprofen was
      obtained by supporting the BGE either with SDS or an amino acid ester-based ionic
      liquid (AAIL). The performance of these additives was evaluated by comparing
      migration times, efficiencies and %RSD values. The addition of the AAIL into the
      BGE provided baseline separation within 10 min, while in the case of SDS, the
      analytes eluted within 23 min. The optimum conditions involve a BGE of 100 mM
      Tris/10 mM sodium tetraboratedecahydrate (pH 8) and 40 mM l-alanine tert butyl
      ester lactate or 10 mM SDS and a temperature of 35 degrees C for AAIL and 20
      degrees C for SDS. The run-to-run reproducibility was evaluated by computing the
      %RSD values of the EOF and the analyte peaks. When the AAIL was used, an
      excellent reproducibility was obtained, since all %RSD values were below 1.3%. On
      the contrary, the addition of SDS resulted in much higher RSD values (2.1-11.7%).
      The efficiency values of all analyte peaks were above 102 000 for l-AlaC4 Lac, in
      comparison to SDS, which provided efficiency values between 47000 and 76000.
      Finally, in an attempt to study the synergistic effect of SDS and AAIL, both
      additives were added into the BGE at concentrations of 10 and 40 mM,
      respectively. The results were similar to the ones obtained when SDS was used as
      the sole additive.

PMID- 24853395
TI  - Transthoracic echocardiographic guidance for obtaining an optimal insertion
      length of internal jugular venous catheters in infants.
AB  - BACKGROUND: There are multiple methods of determining the optimal position of
      central venous catheter (CVC) tips. The purpose of this study was to assess the
      feasibility of transthoracic echocardiography (TTE), and compare TTE and height
      based method for correct positioning of CVCs in infants undergoing cardiac
      surgery. METHODS: Ultrasonography-guided central venous catheterization was
      performed via the right internal jugular vein. Longitudinal images of the right
      atrium and superior vena cava were obtained using TTE. The catheter tip was
      located 10 mm above the crista terminalis. If the catheter tip was not clearly
      visualized, the probe was rotated to obtain transverse images and the CVC tip was
      positioned at the level of the pulmonary artery bifurcation. The mean distance
      from the catheter tip to the level of the carina was compared with that
      calculated using a height-based formula. RESULTS: Among 106 cases, positioning of
      the CVC tip under TTE guidance failed in four patients; thus, the success rate
      was 96.2%. The mean distance from the CVC tip to the level of the carina was
      different for positioning using the TTE method (-3.8 +/- 8.2 mm; 95% confidence
      interval, -5.5 to -2.2 mm) and that using the height-based formula (6.1 +/- 9.6
      mm; 95% CI, 4.2 to 8.0 mm; P = 0.001). The distance was consistent regardless of
      the height when the insertion length was determined using TTE (r = -0.048, P >
      0.05). CONCLUSIONS: Transthoracic echocardiography is a practical method for the
      correct placement of the CVC tip with less variability compared to the height
      based method.

PMID- 24853393
TI  - Circadian rhythms and mood: opportunities for multi-level analyses in genomics
      and neuroscience: circadian rhythm dysregulation in mood disorders provides clues
      to the brain's organizing principles, and a touchstone for genomics and
      neuroscience.
AB  - In the healthy state, both circadian rhythm and mood are stable against
      perturbations, yet they are capable of adjusting to altered internal cues or
      ongoing changes in external conditions. The dual demands of stability and
      flexibility are met by the collective properties of complex neural networks.
      Disruption of this balance underlies both circadian rhythm abnormality and mood
      disorders. However, we do not fully understand the network properties that govern
      the crosstalk between the circadian system and mood regulation. This puzzle
      reflects a challenge at the center of neurobiology, and its solution requires the
      successful integration of existing data across all levels of neural organization,
      from molecules, cells, circuits, network dynamics, to integrated mental function.
      This essay discusses several open questions confronting the cross-level
      synthesis, and proposes that circadian regulation, and its role in mood, stands
      as a uniquely tractable system to study the causal mechanisms of neural
      adaptation. Also watch the Video Abstract. Editor's suggested further reading in
      BioEssays Major depressive disorder: A loss of circadian synchrony? Abstract. 

PMID- 24853396
TI  - The serial nature of the masked onset priming effect revisited.
AB  - Reading aloud is faster when target words/nonwords are preceded by masked prime
      words/nonwords that share their first sound with the target (e.g., save-SINK)
      compared to when primes and targets are unrelated to each other (e.g., farm
      SINK). This empirical phenomenon is the masked onset priming effect (MOPE) and is
      known to be due to serial left-to-right processing of the prime by a sublexical
      reading mechanism. However, the literature in this domain lacks a critical
      experiment. It is possible that when primes are real words their
      orthographic/phonological representations are activated in parallel and
      holistically during prime presentation, so any phoneme overlap between primes and
      targets (and not just initial-phoneme overlap) could facilitate target reading
      aloud. This is the prediction made by the only computational models of reading
      aloud that are able to simulate the MOPE, namely the DRC1.2.1, CDP+, and CDP++
      models. We tested this prediction in the present study and found that initial
      phoneme overlap (blip-BEST), but not end-phoneme overlap (flat-BEST), facilitated
      target reading aloud compared to no phoneme overlap (junk-BEST). These results
      provide support for a reading mechanism that operates serially and from left to
      right, yet are inconsistent with all existing computational models of single-word
      reading aloud. 

PMID- 24853399
TI  - Lymphoid neogenesis in skin of human hand, nonhuman primate, and rat vascularized
      composite allografts.
AB  - The mechanisms of skin rejection in vascularized composite allotransplantation
      (VCA) remain incompletely understood. The formation of tertiary lymphoid organs
      (TLO) in hand transplantation has been recently described. We assess this
      phenomenon in experimental and clinical VCA rejection. Skin biopsies of human (n
      = 187), nonhuman primate (n = 11), and rat (n = 15) VCAs were analyzed for
      presence of TLO. A comprehensive immunohistochemical assessment (characterization
      of the cell infiltrate, expression of adhesion molecules) including staining for
      peripheral node addressin (PNAd) was performed and correlated with rejection and
      time post-transplantation. TLO were identified in human, nonhuman primate, and
      rat skin samples. Expression of PNAd was increased in the endothelium of vessels
      upon rejection in human skin (P = 0.003) and correlated with B- and T-lymphocyte
      numbers and LFA-1 expression. PNAd expression was observed at all time-points
      after transplantation and increased significantly after year 5. In nonhuman
      primate skin, PNAd expression was found during inflammatory conditions early and
      late after transplantation. In rat skin, PNAd expression was strongly associated
      with acute rejection and time post-transplantation. Lymphoid neogenesis and TLO
      formation can be uniformly found in experimental and human VCA. PNAd expression
      in vascular endothelium correlates with skin rejection and T- and B-cell
      infiltration. 

PMID- 24853397
TI  - gammadelta T cells recognize the insulin B:9-23 peptide antigen when it is
      dimerized through thiol oxidation.
AB  - The insulin peptide B:9-23 is a natural antigen in the non-obese diabetic (NOD)
      mouse model of type 1 diabetes (T1D). In addition to alphabeta T cells and B
      cells, gammadelta T cells recognize the peptide and infiltrate the pancreatic
      islets where the peptide is produced within beta cells. The peptide contains a
      cysteine in position 19 (Cys19), which is required for the gammadelta but not the
      alphabeta T cell response, and a tyrosine in position 16 (Tyr16), which is
      required for both. A peptide-specific mAb, tested along with the T cells,
      required neither of the two amino acids to bind the B:9-23 peptide. We found that
      gammadelta T cells require Cys19 because they recognize the peptide antigen in an
      oxidized state, in which the Cys19 thiols of two peptide molecules form a
      disulfide bond, creating a soluble homo-dimer. In contrast, alphabeta T cells
      recognize the peptide antigen as a reduced monomer, in complex with the MHCII
      molecule I-A(g7). Unlike the unstructured monomeric B:9-23 peptide, the
      gammadelta-stimulatory homo-dimer adopts a distinct secondary structure in
      solution, which differs from the secondary structure of the corresponding portion
      of the native insulin molecule. Tyr16 is required for this adopted structure of
      the dimerized insulin peptide as well as for the gammadelta response to it. This
      observation is consistent with the notion that gammadelta T cell recognition
      depends on the secondary structure of the dimerized insulin B:9-23 antigen. 

PMID- 24853400
TI  - Expression of CYP3A in chronic ethanol-fed mice is mediated by endogenous
      pregnane X receptor ligands formed by enhanced cholesterol metabolism.
AB  - Pregnane X receptor (PXR) is a nuclear receptor that plays a key regulatory role
      in xenobiotic metabolism in a ligand-dependent manner. Recently, ethanol was
      reported to be either an inducer or inhibitor of Cytochrome P450 (CYP) 3A
      expression. According to our recent microarray data, chronic ethanol upregulates
      the expression of the genes associated with oxidative phase I drug metabolism,
      phase II conjugation reaction and phase III xenobiotic transport, most of which
      are known to be regulated by PXR. In this study, we investigated the effects of
      chronic ethanol on the expression and activity of CYP3A11 in mice and the role of
      PXR. Ethanol was administrated to male ICR mice by feeding a standard Lieber
      DeCarli diet containing 36 % ethanol for 4 weeks. Ethanol significantly increased
      hepatic mRNA expression of Pxr and Cyp3a11. Treatment of mice with ethanol
      increased nuclear translocation of PXR. Consistent with the increase in nuclear
      PXR, ethanol significantly increased the binding of PXR to the Cyp3a11 promoter.
      Hepatic cholesterol level and bile acid synthesis are increased by ethanol
      treatment. The level of some cholesterol metabolites, such as 5beta-cholestane
      3alpha,7alpha,12alpha-triol, 7alpha-hydroxy-4-cholestene-3-one and lithocholic
      acid, that have been identified as potent PXR agonists are increased in the
      livers of ethanol-treated mice. In summary, chronic ethanol upregulates the
      expression of Pxr and Cyp3a11 mRNAs and proteins in mice by PXR activation
      mediated by enhanced cholesterol metabolism and bile acid synthesis. Our data
      provide some critical information needed to understand the molecular mechanisms
      of ethanol-induced CYP3A expression.

PMID- 24853398
TI  - Effects of strenuous exercise on Th1/Th2 gene expression from human peripheral
      blood mononuclear cells of marathon participants.
AB  - Physical stressors, such as strenuous exercise, can have numerous effects on the
      human body including the immune system. The aim of this study was to evaluate the
      gene expression profile of Th1/Th2 cytokines and related transcription factor
      genes in order to investigate possible immune imbalances before and after a
      marathon. Blood samples were collected from 16 normal volunteers 24-48 h before
      and one week after completing a marathon race. Gene expression of Th1 and Th2
      related cytokines from human peripheral blood mononuclear cells (PBMC) was
      analyzed using Human Th1-Th2-Th3 RT(2) Profiler PCR Array and qRT-PCR that
      measured the transcript levels of 84 genes related to T cell activation. We found
      that PBMC express a characteristic Th2-like gene profile one week post-marathon
      compared to pre-marathon. The majority of genes up-regulated one week post
      marathon such as IL-4, GATA3, and CCR4 were Th2 associated. For Th1-related
      genes, CXCR3 and IRF1 were up-regulated one week post-marathon. There was a trend
      of down-regulation of two Th1 related genes, T-bet and STAT1. Th3-related gene
      expression patterns did not change in the study. The ratios of both IFN-gamma/IL
      4 and T-bet/GATA3 gene expressions were significantly lower one week after
      marathon. These findings suggest that a Th1/Th2 immune imbalance persisted at
      least 1 week after completion of a marathon which offers a mechanistic rationale
      for the increased risk of upper respiratory tract infections often reported after
      strenuous exercise.

PMID- 24853401
TI  - Elevated copper ion levels as potential cause of impaired kinesin-dependent
      transport processes.
AB  - Copper is a trace element required to maintain essential life processes. In
      healthy organisms, copper metabolism is well balanced. If this balance is
      destroyed, the cellular level of free copper might increase and cause toxic
      effects. So far, the molecular mechanisms of copper intoxication are understood
      only partly. The present study revealed that the kinesin-dependent transport
      system is strongly affected by copper(II) ions. Both the microtubules, along
      which kinesin moves, and the kinesin itself were found to be the target
      structures of copper ions: Microtubule formation was suppressed by copper ions
      (IC50 26-70 uM) apparently chiefly by inhibition of binding of microtubule
      associated proteins to tubulin. This inhibition could be widely compensated by
      the microtubule-stabilising agent paclitaxel. In addition, copper ions strongly
      inhibited the ATPase activity of neuron-specific kinesin KIF5A. At final KIF5A
      concentration of 112 nM, an IC50 of 1.3 uM was determined. Correspondingly, the
      motility activity of KIF5A, measured as velocity of microtubules gliding across a
      kinesin-covered surface, was blocked. The effects of copper ions on microtubules
      and on KIF5A are suggested to contribute to impaired transport processes within
      brain and other organs in cases of copper ion surplus.

PMID- 24853402
TI  - Gene expression levels of matrix metalloproteinases in human atherosclerotic
      plaques and evaluation of radiolabeled inhibitors as imaging agents for plaque
      vulnerability.
AB  - INTRODUCTION: Atherosclerotic plaque rupture is the primary cause for myocardial
      infarction and stroke. During plaque progression macrophages and mast cells
      secrete matrix-degrading proteolytic enzymes, such as matrix metalloproteinases
      (MMPs). We studied levels of MMPs and tissue inhibitor of metalloproteinases-3
      (TIMP-3) in relation to the characteristics of carotid plaques. We evaluated in
      vitro two radiolabeled probes targeting active MMPs towards non-invasive imaging
      of rupture-prone plaques. METHODS: Human carotid plaques obtained from
      endarterectomy were classified into stable and vulnerable by visual and
      histological analysis. MMP-1, MMP-2, MMP-8, MMP-9, MMP-10, MMP-12, MMP-14, TIMP
      3, and CD68 levels were investigated by quantitative polymerase chain reaction.
      Immunohistochemistry was used to localize MMP-2 and MMP-9 with respect to CD68
      expressing macrophages. Western blotting was applied to detect their active
      forms. A fluorine-18-labeled MMP-2/MMP-9 inhibitor and a tritiated selective MMP
      9 inhibitor were evaluated by in vitro autoradiography as potential lead
      structures for non-invasive imaging. RESULTS: Gene expression levels of all MMPs
      and CD68 were elevated in plaques. MMP-1, MMP-9, MMP-12 and MMP-14 were
      significantly higher in vulnerable than stable plaques. TIMP-3 expression was
      highest in stable and low in vulnerable plaques. Immunohistochemistry revealed
      intensive staining of MMP-9 in vulnerable plaques. Western blotting confirmed
      presence of the active form in plaque lysates. In vitro autoradiography showed
      binding of both inhibitors to stable and vulnerable plaques. CONCLUSIONS: MMPs
      differed in their expression patterns among plaque phenotypes, providing possible
      imaging targets. The two tested MMP-2/MMP-9 and MMP-9 inhibitors may be useful to
      detect atherosclerotic plaques, but not the vulnerable lesions selectively.

PMID- 24853404
TI  - Going beyond the numbers - a call to redefine polypharmacy.

PMID- 24853403
TI  - Human whole-body biodistribution and dosimetry of a new PET tracer,
      [(11)C]ketoprofen methyl ester, for imagings of neuroinflammation.
AB  - INTRODUCTION: Neuroinflammatory processes play an important role in the
      pathogenesis of Alzheimer's disease and other brain disorders, and nonsteroidal
      anti-inflammatory drugs (NSAIDs) are considered therapeutic candidates. As a
      biomarker of neuroinflammatory processes, (11)C-labeled ketoprofen methyl ester
      ([(11)C]KTP-Me) was designed to allow cerebral penetration of ketoprofen (KTP),
      an active form of a selective cyclooxygenase-1 inhibitor that acts as an NSAID.
      Rat neuroinflammation models indicate that [(11)C]KTP-Me enters the brain and is
      retained in inflammatory lesions, accumulating in activated microglia. [(11)C]KTP
      Me is washed out from normal tissues, leading to the present first-in-human
      exploratory study. METHODS: [(11)C]KTP-Me was synthesized by rapid C
      [(11)C]methylation of [(11)C]CH3I and the corresponding arylacetate precursor,
      purified with high-performance liquid chromatography, and prepared as an
      injectable solution including PEG400, providing radiochemical purity of >99% and
      specific activity of >25GBq/MUmol at injection. Six young healthy male humans
      were injected with [(11)C]KTP-Me and scanned with PET camera to determine the
      early-phase brain time course followed by three whole-body scans starting 8, 20,
      and 40 min post-injection, together with sequential blood sampling and labeled
      metabolite analysis. RESULTS: No adverse effects were observed during PET
      scanning after [(11)C]KTP-Me injection. [(11)C]KTP-Me was rapidly metabolized to
      (11)C-labeled ketoprofen ([(11)C]KTP) within 2-3 min and was gradually cleared
      from blood. The radioactivity entered the brain with an average peak cortical SUV
      of 1.5 at 2 min. The cortical activity was gradually washed out. Whole-body
      images indicated that the urinary bladder was the major excretory pathway. The
      organ with the highest radiation dose was the urinary bladder (average dose of
      41MUGy/MBq, respectively). The mean effective dose was 4.7MUSv/MBq, which was
      comparable to other (11)C-labeled radiopharmaceuticals. CONCLUSION: [(11)C]KTP-Me
      demonstrated a favorable dosimetry, biodistribution, and safety profile.
      [(11)C]KTP-Me entered the human brain, and the radioactivity was washed out from
      cerebral tissue. These data warrant further exploratory studies on patients with
      neuroinflammation.

PMID- 24853405
TI  - Ron Mann: Pharmacoepidemiologist, 1928-2013.

PMID- 24853406
TI  - Synthesis, characterization, and systematic studies of a novel aluminum selective
      chelating resin.
AB  - A procedure is detailed for the selective analysis of trace aluminum by flame
      atomic absorption spectrophotometer coupled with off-line column separation and
      preconcentration. Chelating resin was synthesized by covalent functionalization
      of Amberlite XAD-16 by 2-(2-hydroxyphenyl) benzoxazole. The modified resin was
      characterized using FT-IR spectroscopy, energy dispersive x-ray analysis,
      elemental analysis, thermogravimetric analysis/differential thermal analysis, and
      minimum energy run. The optimum sorption was at pH 9 +/- 0.1 with corresponding
      t(1/2) of only 7 min. Many competitive anions and cations studied did not
      interfere at all in the selective determination of Al(III), at the optimized
      conditions. The resin shows maximum sorption capacity of 21.58 mg g(-1) and can
      be regenerated up to 75 cycles without any discernible capacity loss. The
      Langmuir isotherm model provides the better correlation of the experimental data
      (r(2) = 0.999) in comparison to Freundlich isotherm model, while the Scatchard
      analysis revealed homogeneous binding sites in the chelating resin. Analytical
      figures of merit were evaluated by accuracy (standard reference materials and
      recovery experiment), precision (RSD <5%), and detection limit (2.8 MUg L(-1)).
      The applicability was demonstrated by analysis of trace aluminum in biological,
      environmental, and food samples.

PMID- 24853408
TI  - The impact of aging and Alzheimer's disease on emotional enhancement of memory.
AB  - Emotional enhancement of memory (EEM) has been a well-known phenomenon which
      corresponds to the advantage of emotional stimuli to be better recalled than
      neutral ones. Previous studies suggest that aging favours recollection of
      positive items and this pattern is disrupted in Alzheimer's disease (AD).
      Emotional valence of different stimulus modalities, i.e. pictures and words, may
      also have an effect on each other's memory performances. However, none of these
      were clearly studied in AD. This study aimed to evaluate how emotional valences
      of simultaneously presented stimuli affected recall in healthy young (YG, n =
      30), healthy elderly (HE, n = 30) participants and in patients with AD (n = 30).
      A battery consisting of emotional words presented on emotional pictures was
      developed. An analysis of a 3 (Groups) * 3 (Emotional Valence of Picture) * 3
      (Emotional Valence of Word) mixed ANOVA design was carried out. Patients with AD
      could process emotional information similarly to healthy participants; however,
      they had EEM only for picture recalling. Emotional valence of the co-presented
      stimulus had a boosting effect both in the YG and HE, but not in AD group,
      especially if both of the stimuli had the same emotional valence. This study
      highlights the impaired EEM for verbal and preserved EEM for non-verbal
      declarative memory in patients with AD, the neurobiological underpinnings of
      which should be addressed by future studies.

PMID- 24853407
TI  - Filtration of fullerene and copper oxide nanoparticles using surface-modified
      microfilters.
AB  - This study evaluated the filtration of engineered nanoparticles of fullerene and
      copper oxide (CuO) from water by using surface-modified microsized filters. The
      surfaces of microsized filters of cellulose acetate and glass fibers were coated
      with cationic and anionic surfactants to give them positively and negatively
      charged surfaces, respectively. Uncoated microfilters removed 30% of a fullerene
      suspension, while no nanosized CuO suspension was removed. Cationic surfactant
      coated filters enhanced the removal efficiency up to 70% for the fullerene
      suspension, while the anionic surfactant-coated filters could not remove
      fullerene at all. The positively charged filters with cationic surfactant coating
      could easily adsorb negatively charged fullerenes on their surfaces. However,
      none of the surfactant-coated filters removed the CuO nanoparticles because the
      nanoparticles were not affected by the electrical charge of the filtration
      medium. The Hamaker constants of nanoparticles interacting with the filter
      materials in water were calculated to study these interactions. The Hamaker
      constant of fullerene interacting with cellulose acetate in water, 4.68E - 21 J,
      was higher than that of interacting with quartz in water, 2.59E - 21 J. However,
      the Hamaker constants of CuO interacting with quartz and cellulose acetate in
      water were both negative values, implying repulsive van der Waals interactions.
      The curves of potential energy of interaction between nanoparticles and the
      various filter media implied that the nanoparticles were very stable in water,
      and so, natural deposition of nanoparticles on the filters would not occur.
      Therefore, electrical bonding and hydrophobic interactions were the forces
      dominating fullerene removal by positively charged filters.

PMID- 24853409
TI  - Toward an improved definition of acute-on-chronic liver failure.

PMID- 24853410
TI  - Monomelic amyotrophy: clinical profile and natural history of 279 cases seen over
      35 years (1976-2010).
AB  - Our objective was to study the clinical characteristics and natural history of
      monomelic amyotrophy (MMA). We used a retrospective study of 279 patients
      diagnosed to have either upper (Hirayama disease) or lower limb MMA. Results
      showed that brachial MMA (BMMA) occurred in 224 patients (male:female, 9:1). Mean
      age of onset was 19.5 +/- 4.18 years. Progression occurred over less than five
      years in the majority (95.9%) of patients. Duration at the last follow-up was: up
      to five years in 61.4%, 5-10 in 21.3%, 10-15 in 7.2%, > 15 years in 10.1%. MRI
      showed asymmetrical lower cervical cord atrophy in 44.6% of patients. Crural MMA
      (CMMA) occurred in 55 patients (male:female, 13:1). Mean age of onset was 21.38
      +/- 5.3 years. Similar to BMMA, most cases (65.5%) had onset between 15 and 25
      years of age. Total duration of illness at the last follow-up was up to five
      years in 52.7%, 10 and beyond in 47.3%. In conclusion, a large cohort of patients
      with monomelic amyotrophy seen over 35 years (1976-2010) is described. Study data
      support the clinical findings and its natural history with long term follow-up,
      and the findings emphasize that monomelic amyotrophy is a 'benign' condition with
      a self-limiting course.

PMID- 24853411
TI  - Nucleation and growth synthesis of siloxane gels to form functional,
      monodisperse, and acoustically programmable particles.
AB  - Nucleation and growth methods offer scalable means of synthesizing colloidal
      particles with precisely specified size for applications in chemical research,
      industry, and medicine. These methods have been used to prepare a class of
      silicone gel particles that display a range of programmable properties and narrow
      size distributions. The acoustic contrast factor of these particles in water is
      estimated and can be tuned such that the particles undergo acoustophoresis to
      either the pressure nodes or antinodes of acoustic standing waves. These
      particles can be synthesized to display surface functional groups that can be
      covalently modified for a range of bioanalytical and acoustophoretic sorting
      applications. 

PMID- 24853412
TI  - Knockout of PARG110 confers resistance to cGMP-induced toxicity in mammalian
      photoreceptors.
AB  - Hereditary retinal degeneration (RD) relates to a heterogeneous group of blinding
      human diseases in which the light sensitive neurons of the retina, the
      photoreceptors, die. RD is currently untreatable and the underlying cellular
      mechanisms remain poorly understood. However, the activity of the enzyme poly-ADP
      ribose polymerase-1 (PARP1) and excessive generation of poly-ADP-ribose (PAR)
      polymers in photoreceptor nuclei have been shown to be causally involved in RD.
      The activity of PARP1 is to a large extent governed by its functional antagonist,
      poly-ADP-glycohydrolase (PARG), which thus also may have a role in RD. To
      investigate this, we analyzed PARG expression in the retina of wild-type (wt)
      mice and in the rd1 mouse model for human RD, and detected increased PARG protein
      in a subset of degenerating rd1 photoreceptors. Knockout (KO) animals lacking the
      110 kDa nuclear PARG isoform were furthermore analyzed, and their retinal
      morphology and function were indistinguishable from wild-type animals.
      Organotypic wt retinal explants can be experimentally treated to induce rd1-like
      photoreceptor death, but PARG110 KO retinal explants were unexpectedly highly
      resistant to such treatment. The resistance was associated with decreased PAR
      accumulation and low PARP activity, indicating that PARG110 may positively
      regulate PARP1, an event that therefore is absent in PARG110 KO tissue. Our study
      demonstrates a causal involvement of PARG110 in the process of photoreceptor
      degeneration. Contrasting its anticipated role as a functional antagonist,
      absence of PARG110 correlated with low PARP activity, suggesting that PARG110 and
      PARP1 act in a positive feedback loop, which is especially active under
      pathologic conditions. This in turn highlights both PARG110 and PARP1 as
      potential targets for neuroprotective treatments for RD. 

PMID- 24853413
TI  - Sec-containing TrxR1 is essential for self-sufficiency of cells by control of
      glucose-derived H2O2.
AB  - It is commonly recognized that diabetic complications involve increased oxidative
      stress directly triggered by hyperglycemia. The most important cellular
      protective systems against such oxidative stress have yet remained unclear. Here
      we show that the selenoprotein thioredoxin reductase 1 (TrxR1), encoded by the
      Txnrd1 gene, is an essential enzyme for such protection. Individually grown
      Txnrd1 knockout (Txnrd1(-/-)) mouse embryonic fibroblasts (MEFs) underwent
      massive cell death directly linked to glucose-induced H2O2 production. This death
      and excessive H2O2 levels could be reverted by reconstituted expression of
      selenocysteine (Sec)-containing TrxR1, but not by expression of Sec-devoid
      variants of the enzyme. Our results show that Sec-containing TrxR1 is absolutely
      required for self-sufficient growth of MEFs under high-glucose conditions, owing
      to an essential importance of this enzyme for elimination of glucose-derived
      H2O2. To our knowledge, this is the first time a strict Sec-dependent function of
      TrxR1 has been identified as being essential for mammalian cells. 

PMID- 24853414
TI  - The heat-shock response co-inducer arimoclomol protects against retinal
      degeneration in rhodopsin retinitis pigmentosa.
AB  - Retinitis pigmentosa (RP) is a group of inherited diseases that cause blindness
      due to the progressive death of rod and cone photoreceptors in the retina. There
      are currently no effective treatments for RP. Inherited mutations in rhodopsin,
      the light-sensing protein of rod photoreceptor cells, are the most common cause
      of autosomal-dominant RP. The majority of mutations in rhodopsin, including the
      common P23H substitution, lead to protein misfolding, which is a feature in many
      neurodegenerative disorders. Previous studies have shown that upregulating
      molecular chaperone expression can delay disease progression in models of
      neurodegeneration. Here, we have explored the potential of the heat-shock protein
      co-inducer arimoclomol to ameliorate rhodopsin RP. In a cell model of P23H rod
      opsin RP, arimoclomol reduced P23H rod opsin aggregation and improved viability
      of mutant rhodopsin-expressing cells. In P23H rhodopsin transgenic rat models,
      pharmacological potentiation of the stress response with arimoclomol improved
      electroretinogram responses and prolonged photoreceptor survival, as assessed by
      measuring outer nuclear layer thickness in the retina. Furthermore, treated
      animal retinae showed improved photoreceptor outer segment structure and reduced
      rhodopsin aggregation compared with vehicle-treated controls. The heat-shock
      response (HSR) was activated in P23H retinae, and this was enhanced with
      arimoclomol treatment. Furthermore, the unfolded protein response (UPR), which is
      induced in P23H transgenic rats, was also enhanced in the retinae of arimoclomol
      treated animals, suggesting that arimoclomol can potentiate the UPR as well as
      the HSR. These data suggest that pharmacological enhancement of cellular stress
      responses may be a potential treatment for rhodopsin RP and that arimoclomol
      could benefit diseases where ER stress is a factor. 

PMID- 24853415
TI  - Death-associated protein kinase 1 has a critical role in aberrant tau protein
      regulation and function.
AB  - The presence of tangles composed of phosphorylated tau is one of the
      neuropathological hallmarks of Alzheimer's disease (AD). Tau, a microtubule (MT)
      associated protein, accumulates in AD potentially as a result of
      posttranslational modifications, such as hyperphosphorylation and conformational
      changes. However, it has not been fully understood how tau accumulation and
      phosphorylation are deregulated. In the present study, we identified a novel role
      of death-associated protein kinase 1 (DAPK1) in the regulation of the tau
      protein. We found that hippocampal DAPK1 expression is markedly increased in the
      brains of AD patients compared with age-matched normal subjects. DAPK1
      overexpression increased tau protein stability and phosphorylation at multiple AD
      related sites. In contrast, inhibition of DAPK1 by overexpression of a DAPK1
      kinase-deficient mutant or by genetic knockout significantly decreased tau
      protein stability and abolished its phosphorylation in cell cultures and in mice.
      Mechanistically, DAPK1-enhanced tau protein stability was mediated by Ser71
      phosphorylation of Pin1, a prolyl isomerase known to regulate tau protein
      stability, phosphorylation, and tau-related pathologies. In addition, inhibition
      of DAPK1 kinase activity significantly increased the assembly of MTs and
      accelerated nerve growth factor-mediated neurite outgrowth. Given that DAPK1 has
      been genetically linked to late onset AD, these results suggest that DAPK1 is a
      novel regulator of tau protein abundance, and that DAPK1 upregulation might
      contribute to tau-related pathologies in AD. Therefore, we offer that DAPK1 might
      be a novel therapeutic target for treating human AD and other tau-related
      pathologies. 

PMID- 24853416
TI  - Integrated analyses identify the involvement of microRNA-26a in epithelial
      mesenchymal transition during idiopathic pulmonary fibrosis.
AB  - Idiopathic Pulmonary Fibrosis (IPF) is a chronic, progressive, and highly lethal
      fibrotic lung disease with poor treatment and unknown etiology. Emerging evidence
      suggests that epithelial-mesenchymal transition (EMT) has an important role in
      repair and scar formation following epithelial injury during pulmonary fibrosis.
      Although some miRNAs have been shown to be dysregulated in the pathophysiological
      processes of IPF, limited studies have payed attention on the participation of
      miRNAs in EMT in lung fibrosis. In our study, we identified and constructed a
      regulation network of differentially expressed IPF miRNAs and EMT genes.
      Additionally, we found the downregulation of miR-26a in mice with experimental
      pulmonary fibrosis. Further studies showed that miR-26a regulated HMGA2, which is
      a key factor in the process of EMT and had the maximum number of regulating
      miRNAs in the regulation network. More importantly, inhibition of miR-26a
      resulted in lung epithelial cells transforming into myofibroblasts in vitro and
      in vivo, whereas forced expression of miR-26a alleviated TGF-beta1- and BLM
      induced EMT in A549 cells and in mice, respectively. Taken together, our study
      deciphered the essential role of miR-26a in the pathogenesis of EMT in pulmonary
      fibrosis, and suggests that miR-26a may be a potential therapeutic target for
      IPF. 

PMID- 24853417
TI  - IRE1a constitutes a negative feedback loop with BMP2 and acts as a novel mediator
      in modulating osteogenic differentiation.
AB  - Bone morphogenetic protein 2 (BMP2) is known to activate unfolded protein
      response (UPR) signaling molecules, such as BiP (IgH chain-binding protein), PERK
      (PKR-like ER-resistant kinase), and IRE1alpha. Inositol-requiring enzyme-1a
      (IRE1a), as one of three unfolded protein sensors in UPR signaling pathways, can
      be activated during ER stress. Granulin-epithelin precursor (GEP) is an autocrine
      growth factor that has been implicated in embryonic development, tissue repair,
      tumorigenesis, and inflammation. However, the influence on IRE1a in BMP2-induced
      osteoblast differentiation has not yet been elucidated. Herein we demonstrate
      that overexpression of IRE1a inhibits osteoblast differentiation, as revealed by
      reduced activity of alkaline phosphatase (ALP) and osteocalcin; however,
      knockdown of IRE1a via the RNAi approach stimulates osteoblastogenesis.
      Mechanistic studies revealed that the expression of IRE1a during osteoblast was a
      consequence of JunB transcription factor binding to several AP1 sequence
      (TGAG/CTCA) in the 5'-flanking regulatory region of the IRE1a gene, followed by
      transcription. In addition, GEP induces IRE1a expressions and this induction of
      IRE1a by GEP depends on JunB. Furthermore, IRE1a inhibition of GEP-induced
      osteoblastogenesis relies on JunB. Besides, GEP is required for IRE1a inhibition
      of BMP2-induced bone formation. Collectively, these findings demonstrate that
      IRE1a negatively regulates BMP2-induced osteoblast differentiation and this IRE1a
      inhibition effect depends on GEP growth factor. Thus, IRE1a, BMP2, GEP growth
      factor, and JunB transcription factor form a regulatory loop and act in concert
      in the course of osteoblastogenesis. 

PMID- 24853418
TI  - HKH40A downregulates GRP78/BiP expression in cancer cells.
AB  - HKH40A, the 8-methoxy analog of WMC79, is a synthetic agent with promising in
      vitro and in vivo antitumor activity, especially against solid tumors. However,
      molecular mechanisms underlying its antitumor effects are poorly understood.
      Here, we report that HKH40A markedly reduces the level of GRP78/BiP protein in
      cancer cell lines of various origin. In this study, we show that HKH40A not only
      downregulates transcription of GRP78 but also directly binds to the isolated
      protein and induces its proteosomal degradation. Knockdown of BiP increased the
      efficacy of the drug and overexpression of BiP diminished its activity. BiP is
      generally highly elevated in solid tumors having a pivotal role in cancer cell
      survival and chemoresistance, and has been suggested as a novel target for
      therapeutic intervention. We show that reduction of BiP level by HKH40A impairs
      its function and induces unfolded protein response as evidenced by the activation
      of IRE1alpha, ATF6 and PERK. This leads to a series of downstream events,
      including sustained eIF2alpha phosphorylation, increased abundance of spliced
      XBP1 mRNA and protein levels of ATF4 and CHOP. We also demonstrate that HKH40A
      inhibited tumor formation in an in vivo xenograft tumor model. Collectively, our
      data show that HKH40A reduces BiP levels and this could have an important role in
      the activity of HKH40A against cancer cells. 

PMID- 24853419
TI  - Rasfonin, a novel 2-pyrone derivative, induces ras-mutated Panc-1 pancreatic
      tumor cell death in nude mice.
AB  - Rasfonin is a novel 2-pyrone derivative reported to induce apoptosis in ras
      dependent cells. In this study, its effects on ras-mutated pancreatic cancer
      cells were investigated in vitro and in vivo. Two human pancreatic cancer cell
      lines Panc-1 (mutated K-ras) and BxPC-3 (wild-type K-ras) were selected to test
      the effects of rasfonin on cell proliferation, clone formation, migration and
      invasion in vitro. Immunoblotting was used to detect the expressions of EGFR-Ras
      Raf-MEK-ERK signaling pathway proteins. Ras activity was measured using a pull
      down ELISA kit and guanine exchange factor (GEF)/GTPase-activating proteins (GAP)
      activity was measured by [(3)H]-GDP radiometric ligand binding. For an in vivo
      study, CD1 nude mice bearing Panc-1 cells were treated with rasfonin or Salirasib
      (FTS). We found that rasfonin suppressed proliferation more strongly in Panc-1
      cells (IC50=5.5 MUM) than BxPC-3 cells (IC50=10 MUM) in vitro. Clone formation,
      migration and invasion by Panc-1 cells were also reduced by rasfonin. Rasfonin
      had little effect on the farnesylation of Ras, but it strongly downregulated Ras
      activity and consequently phosphorylation of c-Raf/MEK/ERK. Further experiments
      indicated that rasfonin reduced Son of sevenless (Sos1) expression but did not
      alter GEF and GAP activities. The in vivo experiments also revealed that rasfonin
      (30 mg/kg) delayed the growth of xenograft tumors originating from Panc-1 cells.
      Tumor weight was ultimately decreased after 20 days of treatment of rasfonin.
      Rasfonin is a robust inhibitor of pancreatic cancers with the K-ras mutation. The
      reduction of Sos1 expression and the consequently depressed Ras-MAPK activity
      could be important in its anticancer activity.

PMID- 24853420
TI  - Tip30 controls differentiation of murine mammary luminal progenitor to estrogen
      receptor-positive luminal cell through regulating FoxA1 expression.
AB  - Estrogen receptor-alpha positive (ER(+)) breast cancers comprise the majority of
      human breast cancers, but molecular mechanisms underlying this subtype of breast
      cancers remain poorly understood. Here, we show that ER(+) mammary luminal tumors
      arising in Tip30(-/-)MMTV-Neu mice exhibited increased enrichment of luminal
      progenitor gene signature. Deletion of the Tip30 gene increased proportion of
      mammary stem and progenitor cell populations, and raised susceptibility to ER(+)
      mammary luminal tumors in female Balb/c mice. Moreover, Tip30(-/-) luminal
      progenitors displayed increases in propensity to differentiate to mature ER(+)
      luminal cells and FoxA1 expression. Knockdown of FoxA1 expression in Tip30(-/-)
      progenitors by shRNA specific for FoxA1 reduced their differentiation toward
      ER(+) mature luminal cells. Taken together, our results suggest that TIP30 is a
      key regulator for maintaining ER(+) and ER(-)luminal pools in the mammary luminal
      lineage, and loss of it promotes expansion of ER(+) luminal progenitors and
      mature cells and ER(+) mammary tumorigenesis. 

PMID- 24853421
TI  - P53-regulated long non-coding RNA TUG1 affects cell proliferation in human non
      small cell lung cancer, partly through epigenetically regulating HOXB7
      expression.
AB  - Recently, a novel class of transcripts, long non-coding RNAs (lncRNAs), is being
      identified at a rapid pace. These RNAs have critical roles in diverse biological
      processes, including tumorigenesis. Here we report that taurine-upregulated gene
      1 (TUG1), a 7.1-kb lncRNA, recruiting and binding to polycomb repressive complex
      2 (PRC2), is generally downregulated in non-small cell lung carcinoma (NSCLC)
      tissues. In a cohort of 192 NSCLC patients, the lower expression of TUG1 was
      associated with a higher TNM stage and tumor size, as well as poorer overall
      survival (P<0.001). Univariate and multivariate analyses revealed that TUG1
      expression serves as an independent predictor for overall survival (P<0.001).
      Further experiments revealed that TUG1 expression was induced by p53, and
      luciferase and chromatin immunoprecipitation (ChIP) assays confirmed that TUG1
      was a direct transcriptional target of p53. TUG1 knockdown significantly promoted
      the proliferation in vitro and in vivo. Moreover, the lncRNA-mediated regulation
      of the expression of HOX genes in tumorigenesis and development has been recently
      receiving increased attention. Interestingly, inhibition of TUG1 could upregulate
      homeobox B7 (HOXB7) expression; ChIP assays demonstrated that the promoter of
      HOXB7 locus was bound by EZH2 (enhancer of zeste homolog 2), a key component of
      PRC2, and was H3K27 trimethylated. This TUG1-mediated growth regulation is in
      part due to specific modulation of HOXB7, thus participating in AKT and MAPK
      pathways. Together, these results suggest that p53-regulated TUG1 is a growth
      regulator, which acts in part through control of HOXB7. The p53/TUG1/PRC2/HOXB7
      interaction might serve as targets for NSCLC diagnosis and therapy. 

PMID- 24853422
TI  - Interconnections between autophagy and the coagulation cascade in hepatocellular
      carcinoma.
AB  - Autophagy has an important role in tumor biology of hepatocellular carcinoma
      (HCC). Recent studies demonstrated that tissue factor (TF) combined with
      coagulation factor VII (FVII) has a pathological role by activating a G-protein
      coupled receptor called protease-activated receptor 2 (PAR2) for tumor growth.
      The present study aimed to investigate the interactions of autophagy and the
      coagulation cascade in HCC. Seventy HCC patients who underwent curative liver
      resection were recruited. Immunohistochemical staining and western blotting were
      performed to determine TF, FVII, PAR2 and light chain 3 (LC3A/B) expressions in
      tumors and their contiguous normal regions. We found that the levels of
      autophagic marker LC3A/B-II and coagulation proteins (TF, FVII and PAR2) were
      inversely correlated in human HCC tissues. Treatments with TF, FVII or PAR2
      agonist downregulated LC3A/B-II with an increased level of mTOR in Hep3B cells;
      in contrast, knockdown of TF, FVII or PAR2 increased LC3A/B. Furthermore, mTOR
      silencing restored the impaired expression of LC3A/B-II in TF-, FVII- or PAR2
      treated Hep3B cells and activated autophagy. Last, as an in vivo correlate, we
      administered TF, FVII or PAR2 agonist in a NOD/severe combined immunodeficiency
      xenograft model and showed decreased LC3A/B protein levels in HepG2 tumors with
      treatments. Overall, our present study demonstrated that TF, FVII and PAR2
      regulated autophagy mainly via mTOR signaling. The interaction of coagulation and
      autophagic pathways may provide potential targets for further therapeutic
      application in HCC. 

PMID- 24853424
TI  - Wnt inhibitory factor 1 suppresses cancer stemness and induces cellular
      senescence.
AB  - Hyperactivation of the Wingless-type (Wnt)/beta-catenin pathway promotes tumor
      initiation, tumor growth and metastasis in various tissues. Although there is
      evidence for the involvement of Wnt/beta-catenin pathway activation in salivary
      gland tumors, the precise mechanisms are unknown. Here we report for the first
      time that downregulation of the Wnt inhibitory factor 1 (WIF1) is a widespread
      event in salivary gland carcinoma ex-pleomorphic adenoma (CaExPA). We also show
      that WIF1 downregulation occurs in the CaExPA precursor lesion pleomorphic
      adenoma (PA) and indicates a higher risk of progression from benign to malignant
      tumor. Our results demonstrate that diverse mechanisms including WIF1 promoter
      hypermethylation and loss of heterozygosity contribute to WIF1 downregulation in
      human salivary gland tumors. In accordance with a crucial role in suppressing
      salivary gland tumor progression, WIF1 re-expression in salivary gland tumor
      cells inhibited cell proliferation, induced more differentiated phenotype and
      promoted cellular senescence, possibly through upregulation of tumor-suppressor
      genes, such as p53 and p21. Most importantly, WIF1 significantly diminished the
      number of salivary gland cancer stem cells and the anchorage-independent cell
      growth. Consistent with this observation, WIF1 caused a reduction in the
      expression of pluripotency and stemness markers (OCT4 and c-MYC), as well as
      adult stem cell self-renewal and multi-lineage differentiation markers, such as
      WNT3A, TCF4, c-KIT and MYB. Furthermore, WIF1 significantly increased the
      expression of microRNAs pri-let-7a and pri-miR-200c, negative regulators of
      stemness and cancer progression. In addition, we show that WIF1 functions as a
      positive regulator of miR-200c, leading to downregulation of BMI1, ZEB1 and ZEB2,
      with a consequent increase in downstream targets such as E-cadherin. Our study
      emphasizes the prognostic and therapeutic potential of WIF1 in human salivary
      gland CaExPA. Moreover, our findings demonstrate a novel mechanism by which WIF1
      regulates cancer stemness and senescence, which might have major implications in
      the field of cancer biology. 

PMID- 24853426
TI  - Upregulation and nuclear translocation of testicular ghrelin protects
      differentiating spermatogonia from ionizing radiation injury.
AB  - Proper control of apoptotic signaling is important for maintenance of testicular
      homeostasis after ionizing radiation (IR). Herein, we challenged the hypothesis
      that ghrelin, a pleiotropic modulator, is potentially involved in IR-induced germ
      cell injury. Lower body exposure to 2 Gy of IR induced a notable increase of
      ghrelin expression in the nuclear of differentiating spermatogonia at defined
      stages, with an impairment in the Leydig cells (LCs)-expressing ghrelin.
      Unexpectedly, inhibition of the ghrelin pathway by intraperitoneal injection of a
      specific GHS-R1alpha antagonist enhanced spermatogonia elimination by apoptosis
      during the early recovery following IR, and thereafter resulted in impaired male
      fertility, suggesting that the anti-apoptotic effects of evoked ghrelin, although
      transient along testicular IR injury, have a profound influence on the post
      injury recovery. In addition, inhibition of ghrelin signaling resulted in a
      significant increase in the intratesticular testosterone (T) level at the end of
      21 days after IR, which should stimulate the spermatogenic recovery from
      surviving spermatogonia to a certain extent during the late stage. We further
      demonstrated that the upregulation and nuclear trafficking of ghrelin,
      elaborately regulated by IR-elicited antioxidant system in spermatogonia, may act
      through a p53-dependent mechanism. The elicitation of ghrelin expression by IR
      stress, the regulation of ghrelin expression by IR-induced oxidative stress and
      the interaction between p53 and ghrelin signaling during IR injury were confirmed
      in cultured spermatogonia. Hence, our results represent the first evidence in
      support of a radioprotective role of ghrelin in the differentiating
      spermatogonia. The acutely, delicate regulation of local-produced ghrelin appears
      to be a fine-tune mechanism modulating the balance between testicular homeostasis
      and early IR injury.

PMID- 24853423
TI  - The pleiotropic roles of sphingolipid signaling in autophagy.
AB  - The autophagic process involves encompassing damaged proteins and organelles
      within double- or multi-membraned structures and delivering these molecules to
      the lytic compartments of vacuoles. Sphingolipids (SLs), which are ubiquitous
      membrane lipids in eukaryotes, participate in the generation of various membrane
      structures, including rafts, caveolae, and cytosolic vesicles. SLs are a complex
      family of molecules that have a growing number of members, including ceramide,
      sphingosine-1-phosphate, and dihydroceramide, which have been associated with the
      essential cellular process of autophagy. This review highlights recent studies
      focusing on the regulation and function of SL-associated autophagy and its role
      in cell fate, diseases, and therapeutic interventions. 

PMID- 24853425
TI  - SPAG5 upregulation predicts poor prognosis in cervical cancer patients and alters
      sensitivity to taxol treatment via the mTOR signaling pathway.
AB  - Previously, we found that sperm-associated antigen 5 (SPAG5) was upregulated in
      pelvic lymph node metastasis-positive cervical cancer. The aim of this study is
      to examine the role of SPAG5 in the proliferation and tumorigenicity of cervical
      cancer and its clinical significance in tumor progression. In our study, SPAG5
      expression in cervical cancer patients was detected using quantitative real-time
      polymerase chain reaction, western blotting, and immunohistochemistry; cervical
      cancer cell function with downregulated SPAG5 in vitro was explored using
      tetrazolium assay, flow cytometry, and colony formation and Transwell assays.
      SPAG5 was upregulated in tumor tissue compared with paired adjacent noncancerous
      tissues; SPAG5 upregulation in tumor tissues indicated poor disease-free
      survival, which was also an independent prognostic indicator for cervical cancer
      patients. In vitro study demonstrated that SPAG5 downregulation inhibited cell
      proliferation and growth significantly by G2/M arrest and induction of apoptosis,
      and hindered cell migration and invasion. Under SPAG5 downregulation, the
      sensitivity of cervical cancer cells differed according to taxol dose, which
      correlated with mammalian target of rapamycin (mTOR) signaling pathway activity.
      In general, SPAG5 upregulation relates to poor prognosis in cervical cancer
      patients, and SPAG5 is a regulator of mTOR activity during taxol treatment in
      cervical cancer. 

PMID- 24853427
TI  - The CT20 peptide causes detachment and death of metastatic breast cancer cells by
      promoting mitochondrial aggregation and cytoskeletal disruption.
AB  - Metastasis accounts for most deaths from breast cancer, driving the need for new
      therapeutics that can impede disease progression. Rationally designed peptides
      that take advantage of cancer-specific differences in cellular physiology are an
      emerging technology that offer promise as a treatment for metastatic breast
      cancer. We developed CT20p, a hydrophobic peptide based on the C terminus of Bax
      that exhibits similarities with antimicrobial peptides, and previously reported
      that CT20p has unique cytotoxic actions independent of full-length Bax. In this
      study, we identified the intracellular actions of CT20p which precede cancer cell
      specific detachment and death. Previously, we found that CT20p migrated in the
      heavy membrane fractions of cancer cell lysates. Here, using MDA-MB-231 breast
      cancer cells, we demonstrated that CT20p localizes to the mitochondria, leading
      to fusion-like aggregation and mitochondrial membrane hyperpolarization. As a
      result, the distribution and movement of mitochondria in CT20p-treated MDA-MB-231
      cells was markedly impaired, particularly in cell protrusions. In contrast, CT20p
      did not associate with the mitochondria of normal breast epithelial MCF-10A
      cells, causing little change in the mitochondrial membrane potential, morphology
      or localization. In MDA-MB-231 cells, CT20p triggered cell detachment that was
      preceded by decreased levels of alpha5beta1 integrins and reduced F-actin
      polymerization. Using folate-targeted nanoparticles to encapsulate and deliver
      CT20p to murine tumors, we achieved significant tumor regression within days of
      peptide treatment. These results suggest that CT20p has application in the
      treatment of metastatic disease as a cancer-specific therapeutic peptide that
      perturbs mitochondrial morphology and movement ultimately culminating in
      disruption of the actin cytoskeleton, cell detachment, and loss of cell
      viability. 

PMID- 24853428
TI  - Altered expression of Alzheimer's disease-related genes in the cerebellum of
      autistic patients: a model for disrupted brain connectome and therapy.
AB  - Autism and Alzheimer's disease (AD) are, respectively, neurodevelopmental and
      degenerative diseases with an increasing epidemiological burden. The AD
      associated amyloid-beta precursor protein-alpha has been shown to be elevated in
      severe autism, leading to the 'anabolic hypothesis' of its etiology. Here we
      performed a focused microarray analysis of genes belonging to NOTCH and WNT
      signaling cascades, as well as genes related to AD and apoptosis pathways in
      cerebellar samples from autistic individuals, to provide further evidence for
      pathological relevance of these cascades for autism. By using the limma package
      from R and false discovery rate, we demonstrated that 31% (116 out of 374) of the
      genes belonging to these pathways displayed significant changes in expression
      (corrected P-values <0.05), with mitochondria-related genes being the most
      downregulated. We also found upregulation of GRIN1, the channel-forming subunit
      of NMDA glutamate receptors, and MAP3K1, known activator of the JNK and ERK
      pathways with anti-apoptotic effect. Expression of PSEN2 (presinilin 2) and APBB1
      (or F65) were significantly lower when compared with control samples. Based on
      these results, we propose a model of NMDA glutamate receptor-mediated ERK
      activation of alpha-secretase activity and mitochondrial adaptation to apoptosis
      that may explain the early brain overgrowth and disruption of synaptic plasticity
      and connectome in autism. Finally, systems pharmacology analyses of the model
      that integrates all these genes together (NOWADA) highlighted magnesium (Mg(2+))
      and rapamycin as most efficient drugs to target this network model in silico.
      Their potential therapeutic application, in the context of autism, is therefore
      discussed. 

PMID- 24853429
TI  - Sulfur dioxide inhibits vascular smooth muscle cell proliferation via suppressing
      the Erk/MAP kinase pathway mediated by cAMP/PKA signaling.
AB  - The present study was designed to investigate the role of endogenous sulfur
      dioxide (SO2) in vascular smooth muscle cell (VSMC) proliferation, and explore
      the possible role of cross-talk between cyclic adenosine monophosphate
      (cAMP)/protein kinase A (PKA) and extracellular signal-regulated kinase
      (Erk)/mitogen-activated protein kinase (MAPK) pathways in this action. By cell
      counting, growth curve depict, flow cytometry and bromodeoxyuridine (BrdU)
      labeling assays, we found that SO2 inhibited VSMC proliferation by preventing
      cell cycle progression from G1 to S phase and by reducing DNA synthesis. SO2
      synthase aspartate aminotransferase (AAT1 and AAT2) overexpression significantly
      inhibited serum-induced proliferating cell nuclear antigen (PCNA) protein
      expression in VSMCs, demonstrated by western blot analysis. Moreover,
      overexpression of AAT1 or AAT2 markedly reduced incorporation of BrdU in serum
      treated VSMCs. By contrast, either AAT1 or AAT2 knockdown significantly
      exacerbated serum-stimulated VSMC proliferation. Thus, both exogenous- and
      endogenous-derived SO2 suppressed serum-induced VSMC proliferation. However,
      annexin V-propidium iodide (PI) staining and cell cycle analysis demonstrated
      that SO2 did not influence VSMC apoptosis in the serum-induced proliferation
      model. In a platelet-derived growth factor (PDGF)-BB-stimulated VSMC
      proliferation model, SO2 dephosphorylated the active sites of Erk1/2, MAPK kinase
      1/2 and RAF proto-oncogene serine/threonine-protein kinase (c-Raf) induced by
      PDGF-BB. However, the inactivation of the three kinases of the Erk/MAPK pathway
      was not due to the separate interferences on them by SO2 simultaneously, but a
      consequence of the influence on the upstream activity of the c-Raf molecule.
      Hence, we examined the cAMP/PKA pathway, which could inhibit Erk/MAPK
      transduction in VSMCs. The results showed that SO2 could stimulate the cAMP/PKA
      pathway to block c-Raf activation, whereas the Ser259 site on c-Raf had an
      important role in SO2-induced suppression of Erk/MAPK pathway. The present study
      firstly demonstrated that SO2 exerted a negative regulation of VSMC proliferation
      via suppressing the Erk/MAPK pathway mediated by cAMP/PKA signaling. 

PMID- 24853430
TI  - Non-viral FoxM1 gene delivery to hepatocytes enhances liver repopulation.
AB  - Hepatocyte transplantation as a substitute strategy of orthotopic liver
      transplantation is being studied for treating end-stage liver diseases. Several
      technical hurdles must be overcome in order to achieve the therapeutic liver
      repopulation, such as the problem of insufficient expansion of the transplanted
      hepatocytes in recipient livers. In this study, we analyzed the application of
      FoxM1, a cell-cycle regulator, to enhance the proliferation capacity of
      hepatocytes. The non-viral sleeping beauty (SB) transposon vector carrying FoxM1
      gene was constructed for delivering FoxM1 into the hepatocytes. The proliferation
      capacities of hepatocytes with FoxM1 expression were examined both in vivo and in
      vitro. Results indicated that the hepatocytes with FoxM1 expression had a higher
      proliferation rate than wild-type (WT) hepatocytes in vitro. In comparison with
      WT hepatocytes, the hepatocytes with FoxM1 expression had an enhanced level of
      liver repopulation in the recipient livers at both sub-acute injury (fumaryl
      acetoacetate hydrolase (Fah)(-/-) mice model) and acute injury (2/3 partial
      hepatectomy mice model). Importantly, there was no increased risk of
      tumorigenicity with FoxM1 expression in recipients even after serial
      transplantation. In conclusion, expression of FoxM1 in hepatocytes enhanced the
      capacity of liver repopulation without inducing tumorigenesis. FoxM1 gene
      delivered by non-viral SB vector into hepatocytes may be a viable approach to
      promote therapeutic repopulation after hepatocyte transplantation. 

PMID- 24853431
TI  - DNA replication stress in CHK1-depleted tumour cells triggers premature (S-phase)
      mitosis through inappropriate activation of Aurora kinase B.
AB  - The disruption of DNA replication in cells triggers checkpoint responses that
      slow-down S-phase progression and protect replication fork integrity. These
      checkpoints are also determinants of cell fate and can help maintain cell
      viability or trigger cell death pathways. CHK1 has a pivotal role in such S-phase
      responses. It helps maintain fork integrity during replication stress and
      protects cells from several catastrophic fates including premature mitosis,
      premature chromosome condensation and apoptosis. Here we investigated the role of
      CHK1 in protecting cancer cells from premature mitosis and apoptosis. We show
      that premature mitosis (characterized by the induction of histone H3
      phosphorylation, aberrant chromatin condensation, and persistent RPA foci in
      arrested S-phase cells) is induced in p53-deficient tumour cells depleted of CHK1
      when DNA synthesis is disrupted. These events are accompanied by an activation of
      Aurora kinase B in S-phase cells that is essential for histone H3 Ser10
      phosphorylation. Histone H3 phosphorylation precedes the induction of apoptosis
      in p53-/- tumour cell lines but does not appear to be required for this fate as
      an Aurora kinase inhibitor suppresses phosphorylation of both Aurora B and
      histone H3 but has little effect on cell death. In contrast, only a small
      fraction of p53+/+ tumour cells shows this premature mitotic response, although
      they undergo a more rapid and robust apoptotic response. Taken together, our
      results suggest a novel role for CHK1 in the control of Aurora B activation
      during DNA replication stress and support the idea that premature mitosis is a
      distinct cell fate triggered by the disruption of DNA replication when CHK1
      function is suppressed. 

PMID- 24853434
TI  - Effect of the number of coloring liquid applications on the optical properties of
      monolithic zirconia.
AB  - OBJECTIVE: This study was aimed to investigate the effect of the number of
      coloring liquid applications on the optical properties of monolithic zirconia.
      METHODS: Eighteen monolithic zirconia specimens (27.6 mm*27.6 mm*2.0 mm) were
      fabricated and divided into 6 groups (n=3). Each group was designated by the
      number of A2-coloring liquid applications (Group I to Group V) and Group O as a
      control. Color and spectral distribution of the specimens were measured with a
      double-beam spectrophotometer. CIE L*, a* and b* relative to the standard
      illuminants D65 were measured in reflectance and transmittance modes. Color
      difference (DeltaEab*), translucency parameter (TP) and opalescence parameter
      (OP) were calculated. All measurements were performed on five different areas of
      each specimen. All data were analyzed by ANOVA and multiple comparison Scheffe
      test, Pearson correlations and linear regression analysis (alpha=0.05). RESULTS:
      With the increase of the number of coloring liquid applications, CIE L*
      (R2=0.878) and OP values (R2=0.701) were decreased, but CIE b* (R2=0.938) was
      increased. However, TP values were not significantly changed. The color
      differences among groups ranged from 1.3 to 15.7 DeltaEab* units. Strong
      correlation was found between OP and Deltab* (R2=0.982, P<.01). SIGNIFICANCE:
      Within the limitations of this study, it can be concluded that the number of
      coloring liquid applications with a single shade affects the lightness, yellow
      chromaticity and opalescence of monolithic zirconia, although its translucency
      cannot be controlled by the coloring procedure.

PMID- 24853435
TI  - First titanium dental implants with white surfaces: preparation and in vitro
      tests.
AB  - OBJECTIVES: To evaluate first white titanium surfaces developed for improvement
      of existing clinically used titanium-based implants Ticer. METHODS: The anodic
      plasma-electrochemical oxidation in aqueous solutions of sodium hydroxide and
      calcium dihydrogen phospate was used to prepare three novel anodic conversion
      layers with white titanium oxide surfaces. The surfaces have been characterized
      by the means of scanning electron microscopy, surface microanalysis and X-ray
      diffraction. In vitro studies were conducted on primary human osteoblast cells
      using novel surfaces (M1-M3) as well as commercially pure titanium (Ti cp), Ticer
      and SS (subtracted surface). An indirect toxicity test using MTT and SRB assays
      has been carried out. Furthermore, immunohistochemical analysis of cell
      proliferation, morphology, and expression of non-collagenous bone matrix proteins
      (sialoprotein, BSP, and osteocalcin, OC) were performed. RESULTS: The basic
      morphology of the surfaces shows clusters in a size of 100 MUm of knob-like
      structures. The coatings are composed of rutile and monoclinic sodium titanates.
      Novel white surfaces (M1-M3) induced proliferation rates, morphological changes
      and influenced the expression of OC and BSP similarly to Ticer. On the other
      hand, Ti cp and SS exhibited different in vitro behavior. SIGNIFICANCE: The novel
      surfaces expressed similar in vitro behavior as Ticer, successfully used in
      clinical practice. Furthermore, due to their white color they are also promising
      from the esthetic point of view. The results described herein open the door
      toward a new generation of white titanium dental implants.

PMID- 24853436
TI  - In vitro dosimetry of agglomerates.
AB  - Agglomeration of nanoparticles in biological fluids is a pervasive phenomenon
      that leads to difficulty in the interpretation of results from in vitro exposure,
      primarily due to differing particokinetics of agglomerates to nanoparticles.
      Therefore, well-defined small agglomerates were designed that possessed different
      particokinetic profiles, and their cellular uptake was compared to a
      computational model of dosimetry. The approach used here paves the way for a
      better understanding of the impact of agglomeration on the nanoparticle-cell
      interaction. 

PMID- 24853437
TI  - Bile duct perforation caused by an uncovered metal stent treated by placement of
      a covered metal stent in a patient with pancreatic cancer.

PMID- 24853433
TI  - Radiation induces senescence and a bystander effect through metabolic
      alterations.
AB  - Cellular senescence is a state of irreversible growth arrest; however, the
      metabolic processes of senescent cells remain active. Our previous studies have
      shown that radiation induces senescence of human breast cancer cells that display
      low expression of securin, a protein involved in control of the metaphase
      anaphase transition and anaphase onset. In this study, the protein expression
      profile of senescent cells was resolved by two-dimensional gel electrophoresis to
      investigate associated metabolic alterations. We found that radiation induced the
      expression and activation of glyceraldehyde-3-phosphate dehydrogenase that has an
      important role in glycolysis. The activity of lactate dehydrogenase A, which is
      involved in the conversion of pyruvate to lactate, the release of lactate and the
      acidification of the extracellular environment, was also induced. Inhibition of
      glycolysis by dichloroacetate attenuated radiation-induced senescence. In
      addition, radiation also induced activation of the 5'-adenosine monophosphate
      activated protein kinase (AMPK) and nuclear factor kappa B (NF-kappaB) pathways
      to promote senescence. We also found that radiation increased the expression of
      monocarboxylate transporter 1 (MCT1) that facilitates the export of lactate into
      the extracellular environment. Inhibition of glycolysis or the AMPK/NF-kappaB
      signalling pathways reduced MCT1 expression and rescued the acidification of the
      extracellular environment. Interestingly, these metabolic-altering signalling
      pathways were also involved in radiation-induced invasion of the surrounding, non
      irradiated breast cancer and normal endothelial cells. Taken together, radiation
      can induce the senescence of human breast cancer cells through metabolic
      alterations. 

PMID- 24853439
TI  - Combined use of covered and uncovered self-expandable metal stents in patients
      with bleeding, obstructing stage IV colorectal cancer.

PMID- 24853438
TI  - Modified single-balloon endoscopy for ERCP in a patient with Billroth II
      gastrectomy.

PMID- 24853440
TI  - A case of delayed bleeding 9 days after endoscopic ultrasound-guided pancreatic
      pseudocyst drainage.

PMID- 24853441
TI  - Strangulated umbilical hernia after esophagogastroduodenoscopy in a patient with
      liver cirrhosis and ascites.

PMID- 24853443
TI  - Life-threatening air embolism during ERCP.

PMID- 24853442
TI  - Intraductal papillary carcinoma of common bile duct diagnosed by endoscopic
      ultrasound-guided fine-needle aspiration.

PMID- 24853444
TI  - Synchronous sporadic gastrointestinal stromal tumors (GISTs) of the colon.

PMID- 24853445
TI  - Intramural hematoma with gastric outlet obstruction: a rare complication of
      endoscopic injection therapy for bleeding anastomotic ulcer.

PMID- 24853446
TI  - Jejunal diverticular bleeding treated using cap-assisted enteroscopy: pulling the
      plug.

PMID- 24853447
TI  - A new suturing procedure for closure of a gastrocutaneous fistula.

PMID- 24853448
TI  - Redeployment of proximally misplaced self-expandable metallic stent in an
      inoperable esophageal carcinoma, using an overtube technique.

PMID- 24853449
TI  - Impacted bone fragment in a small-bowel diverticulum: an extremely rare cause of
      obscure gastrointestinal bleeding.

PMID- 24853450
TI  - Constipation and cow's milk allergy: a review of the literature.
AB  - The causal association between cow's milk allergy (CMA) and constipation is not
      well established. Some guidelines describe constipation as a possible symptom of
      CMA, while others do not mention it. We conducted a literature review and found
      10 prospective clinical trials. In all of them, an oral food challenge was
      performed, and 2 of them were randomized. These studies reported that a cow's
      milk (CM) protein-free diet has a beneficial effect on constipation, with a rate
      of successful outcomes ranging from 28 to 78%. The hypothetic pathogenic
      mechanism lies in increased anal pressure at rest, probably caused by allergic
      inflammation of the internal sphincter area due to mucosal eosinophil and mast
      cell infiltration. Eighty percent of patients reach tolerance within 1 year after
      the diagnosis of CMA-related constipation. We believe that a CM-free diet for 2-4
      weeks should be proposed for children with chronic functional constipation, even
      if it is not severe or resistant to laxatives.

PMID- 24853451
TI  - Activity classification based on inertial and barometric pressure sensors at
      different anatomical locations.
AB  - Miniature, wearable sensor modules are a promising technology to monitor
      activities of daily living (ADL) over extended periods of time. To assure both
      user compliance and meaningful results, the selection and placement site of
      sensors requires careful consideration. We investigated these aspects for the
      classification of 16 ADL in 6 healthy subjects under laboratory conditions using
      ReSense, our custom-made inertial measurement unit enhanced with a barometric
      pressure sensor used to capture activity-related altitude changes. Subjects wore
      a module on each wrist and ankle, and one on the trunk. Activities comprised
      whole body movements as well as gross and dextrous upper-limb activities. Wrist
      module data outperformed the other locations for the three activity groups.
      Specifically, overall classification accuracy rates of almost 93% and more than
      95% were achieved for the repeated holdout and user-specific validation methods,
      respectively, for all 16 activities. Including the altitude profile resulted in a
      considerable improvement of up to 20% in the classification accuracy for stair
      ascent and descent. The gyroscopes provided no useful information for activity
      classification under this scheme. The proposed sensor setting could allow for
      robust long-term activity monitoring with high compliance in different patient
      populations. 

PMID- 24853452
TI  - Competing risks model in screening for preeclampsia by serum placental growth
      factor and soluble fms-like tyrosine kinase-1 at 30-33 weeks' gestation.
AB  - OBJECTIVE: To assess the risk for preeclampsia (PE) by maternal characteristics,
      serum placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt
      1) at 30-33 weeks' gestation. METHODS: This was a screening study in singleton
      pregnancies including 2,140 that subsequently developed PE and 83,615 that were
      unaffected by PE, gestational hypertension or delivery of small-for-gestational
      age neonates (normal group). We developed a survival time model for the time of
      delivery for PE by combination of maternal characteristics and history with PlGF
      and sFlt-1 multiple of the median (MoM) values (biochemical test). Data on third
      trimester PlGF and sFlt-1 were available in 118 cases of PE and 3,734 of normal
      group. The detection rate (DR) of PE requiring delivery within 4, 6 and 8 weeks
      of the visit was estimated. RESULTS: In pregnancies with PE, the log10 MoM values
      of PlGF and sFlt-1 were linearly related to gestational age at delivery.
      Screening by the biochemical test detected 100, 76, and 62% of PE with delivery
      within 4, 6 and 8 weeks of the visit, at a fixed false-positive rate of 5%.
      INTERPRETATION: Testing by PlGF and sFlt-1 at 30-33 weeks could identify all
      pregnancies developing PE and requiring delivery within the subsequent 4 weeks.

PMID- 24853453
TI  - Synthesis, molecular docking and biological evaluation of glycyrrhizin analogs as
      anticancer agents targeting EGFR.
AB  - Glycyrrhizin (GA) analogs in the form of 3-glucuronides and 18-epimers were
      synthesized and their anticancer activities were evaluated. Alkaline
      isomerization of monoglucuronides is reported. In vitro and in vivo studies
      showed that glycyrrhetinic acid monoglucuronides (GAMGs) displayed higher
      anticancer activities than those of bisglucuronide GA analogs, while anticancer
      activity of the 18alpha-epimer was superior to that of the 18beta-epimer. 18alpha
      GAMG was firstly nicely bound to epidermal growth factor receptor (EGFR) via six
      hydrogen bonds and one charge interaction, and the docking calculation proved the
      correlation between anticancer activities and EGFR inhibitory activities. Highly
      active 18alpha-GAMG is thus of interest for the further studies as a potential
      anticancer agent. 

PMID- 24853454
TI  - (60)Co-gamma irradiation affects the enzymatic antioxidant system of the citrus
      red mite Panonychus citri (Acari: Tetranychidae).
AB  - Radio-(60Co), which emits gamma rays, has been used worldwide in pest control.
      The aim of the present study was to analyze the effect of effective-low-power
      60Co-gamma irradiation on the enzymatic antioxidant system of the citrus red mite
      Panonychus citri. One day old female adults were exposed to 0.4 kGy 60Co-gamma
      irradiation and on the, 6th h, 1st day, 2nd day, and 5th day post treatment, the
      mites were euthanized for biochemical analysis. The activity of superoxide
      dismutase (SOD), catalase (CAT), peroxidase (POD), phenoloxidase (PO) and
      acetylocholinesterase (AchE) were investigated. POD and CAT activities, as well
      as SOD were higher in the irradiated mites. We found that exposure to 60Co-gamma
      radiation resulted in increased activities of SOD, CAT, POD and decreased AchE
      activity. When the recovery time lasted till the 5th day, the activities of POD
      and PO were significantly lower than the control, whereas the SOD, CAT and AchE
      activities returned to control levels. Cells possess protein repair pathways to
      rescue oxidized proteins and restore their functions, but if these repair
      processes fail, oxidized proteins may become cytotoxic. Our results confirm the
      hypothesis that low dosages of 60Co-gamma irradiation increase the level of
      oxidative stress in P. citri adults in a short time, causing meanwhile damage and
      sterility. The results of this study also indicate that stress caused by exposure
      to irradiation could inhibit the cholinergic system in P. citri. 

PMID- 24853455
TI  - The role of micro-RNAs in hepatocellular carcinoma: from molecular biology to
      treatment.
AB  - Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the
      third leading cause of cancer deaths. microRNAs (miRNAs) are evolutionary
      conserved small non-coding RNA that negatively regulate gene expression and
      protein translation. Recent evidences have shown that they are involved in many
      biological processes, from development and cell-cycle regulation to apoptosis.
      miRNAs can behave as tumor suppressor or promoter of oncogenesis depending on the
      cellular function of their targets. Moreover, they are frequently dysregulated in
      HCC. In this review we summarize the latest findings of miRNAs regulation in HCC
      and their role as potentially diagnostic and prognostic biomarkers for HCC. We
      highlight development of miRNAs as potential therapeutic targets for HCC. 

PMID- 24853456
TI  - Graphene-multiwall carbon nanotube-gold nanocluster composites modified electrode
      for the simultaneous determination of ascorbic acid, dopamine, and uric acid.
AB  - In this paper, graphene-multiwall carbon nanotube-gold nanocluster (GP-MWCNT
      AuNC) composites were synthesized and used as modifier to fabricate a sensor for
      simultaneous detection of ascorbic acid (AA), dopamine (DA), and uric acid (UA).
      The electrochemical behavior of the sensor was investigated by electrochemical
      impedance spectroscopy (EIS), cyclic voltammetry (CV) and differential pulse
      voltammetry (DPV) techniques. The combination of GP, MWCNTs, and AuNCs endowed
      the electrode with a large surface area, good catalytic activity, and high
      selectivity and sensitivity. The linear response range for simultaneous detection
      of AA, DA, and UA at the sensor were 120-1,701, 2-213, and 0.7-88.3 MUM,
      correspondingly, and the detection limits were 40, 0.67, and 0.23 MUM (S/N=3),
      respectively. The proposed method offers a promise for simple, rapid, selective,
      and cost-effective analysis of small biomolecules.

PMID- 24853457
TI  - Injection drug use is associated with suicide attempts but not ideation or plans
      in a sample of adolescents with depressive symptoms.
AB  - OBJECTIVE: Based on the interpersonal theory of suicide, pain habituation that
      occurs with injection substance use may raise risk for a suicide attempt. The
      current study tested whether injection substance use, relative to painless routes
      of substance administration, was related to greater risk for suicide attempts. We
      also assessed whether this risk was specific to suicide attempts and not suicidal
      ideation or suicide plans. METHODS: Data on 2095 substance-using adolescents aged
      12-17 who endorsed clinically significant depression symptoms and answered
      questions on suicidal thoughts and behavior were drawn from the 2004-2011
      National Survey on Drug Use and Health, a nationally representative household
      survey. Logistic regression analyses were conducted to assess the associations
      between injection substance use and suicidal ideation, plans, and attempts.
      RESULTS: Injection substance use was associated with suicide attempts (OR = 3.02,
      95% CI = 1.75-5.23) but not ideation or plans. These findings were not accounted
      for by sex, age, race/ethnicity, family income, abuse and dependence symptoms,
      and depression symptoms. Among ideators, injection substance use was associated
      with suicide attempts (OR = 2.92, 95% CI = 1.58-5.06), but not plans. Among
      suicide planners, injection substance use was associated with suicide attempts
      (OR = 5.16, 95% CI = 1.88-14.17). CONCLUSION: Consistent with the interpersonal
      theory of suicide, adolescent injection drug use was associated with specific
      risk for suicide attempts but not ideation or planning. Hence, consideration of
      the manner in which adolescents use substances is important in evaluating suicide
      risk in this population.

PMID- 24853459
TI  - Continuous manufacturing of solid lipid nanoparticles by hot melt extrusion.
AB  - Solid lipid nanoparticles (SLN) can either be produced by hot homogenization of
      melted lipids at higher temperatures or by a cold homogenization process. This
      paper proposes and demonstrates the formulation of SLN for pharmaceutical
      applications by combining two processes: hot melt extrusion (HME) technology for
      melt-emulsification and high-pressure homogenization (HPH) for size reduction.
      This work aimed at developing continuous and scalable processes for SLN by mixing
      a lipid and aqueous phase containing an emulsifier in the extruder barrel at
      temperatures above the melting point of the lipid and further reducing the
      particle size of emulsion by HPH linked to HME in a sequence. The developed novel
      platform demonstrated better process control and size reduction compared to the
      conventional process of hot homogenization (batch process). Varying the process
      parameters enabled the production of SLN below 200 nm (for 60 mg/ml lipid
      solution at a flow rate of 100ml/min). Among the several process parameters
      investigated, the lipid concentration, residence time and screw design played
      major roles in influencing the size of the SLN. This new process demonstrates the
      potential use of hot melt extrusion technology for continuous and large-scale
      production of SLN.

PMID- 24853458
TI  - Association of COMT and PRODH gene variants with intelligence quotient (IQ) and
      executive functions in 22q11.2DS subjects.
AB  - The 22q11.2 deletion syndrome (22q11.2DS) carries the highest genetic risk factor
      for the development of schizophrenia. We investigated the association of genetic
      variants in two schizophrenia candidate genes with executive function (EF) and IQ
      in 22q11.2DS individuals. Ninety two individuals with 22q11.2 deletion were
      studied for the genetic association between COMT and PRODH variants and EF and
      IQ. Subjects were divided into children (under 12 years old), adolescents
      (between 12 and 18 years old) and adults (older than 18 years), and genotyped for
      the COMT Val158Met (rs4680) and PRODH Arg185Trp (rs4819756) polymorphisms. The
      participants underwent psychiatric evaluation and EF assessment. Our main finding
      is a significant influence of the COMT Val158Met polymorphism on both IQ and EF
      performance. Specifically, 22q11.2DS subjects with Met allele displayed higher IQ
      scores in all age groups compared to Val carriers, reaching significance in both
      adolescents and adults. The Met allele carriers performed better than Val
      carriers in EF tasks, being statistically significant in the adult group. PRODH
      Arg185Trp variant did not affect IQ or EF in our 22q11.2DS cohort. In conclusion,
      functional COMT variant, but not PRODH, affects IQ and EF in 22q11.2DS subjects
      during neurodevelopment with a maximal effect at adulthood. Future studies should
      monitor the cognitive performance of the same individuals from childhood to old
      age. 

PMID- 24853461
TI  - Incorporation of cisplatin into PEG-wrapped ultrapurified large-inner-diameter
      MWCNTs for enhanced loading efficiency and release profile.
AB  - The efficacy of carbon nanotubes based drug delivery systems (DDSs) has long been
      compromised by low drug loading efficiency and rapid release profile, especially
      for drugs encapsulated inside nanotubes. To address these deficiencies, the large
      inner-diameter multi-walled carbon nanotubes (LID-MWCNTs) were employed to
      synthesize an innovative cisplatin (CDDP)-loaded DDS. A multi-step purification
      and oxidation procedure was developed to achieve ultrapurified oxidized LID
      MWCNTs prior to entrapping CDDP. High molecular weight polyethylene glycol (PEG)
      was grafted onto the nanotubes to partially block the exit paths of drugs. As
      assessed by TGA and ICP-OES analyses, CDDP loading efficiency of resulting DDS
      was as high as 100.12%, and sustained release profile was obtained. Finally, the
      anticancer activity on CAL-27 cells was evaluated, and enhanced inhibition effect
      (IC50 values 3.93 MUg/ml) was recorded. The successful inner-cavity-loading of
      LID-MWCNTs also provides a basis for establishing more complicated multi
      functional DDSs.

PMID- 24853462
TI  - The role of the stomach in drug absorption as observed via absorption rate
      analysis.
AB  - Absorption rate analysis (ARA) was introduced in 2011 as a no-cost investigative
      tool for elucidating the details of drug absorption recorded in individual plasma
      time-concentration profiles. The method continues to be refined since its
      introduction, so that a new article offering more advanced applications of the
      method is appropriate. The stomach has been observed to exert considerable
      influence on the drug absorption process beyond the usual issues of drug
      solubility and stability in the gastric environment. This article is intended to
      demonstrate how readers can use ARA to reveal common factors affecting drug
      absorption. A newly introduced technique is to make observations concerning
      individual subjects, then assemble those individual observations to reveal
      factors not observable on an individual basis. This technique considerably
      increases the utility of ARA for revealing potential barriers to drug absorption.

PMID- 24853460
TI  - Docetaxel-carboxymethylcellulose nanoparticles display enhanced anti-tumor
      activity in murine models of castration-resistant prostate cancer.
AB  - Docetaxel (DTX) remains the only effective drug for prolonging survival and
      improving quality of life of metastatic castration resistant prostate cancer
      (mCRPC) patients. Despite some clinical successes with DTX-based therapies,
      advent of cumulative toxicity and development of drug resistance limit its long
      term clinical application. The integration of nanotechnology for drug delivery
      can be exploited to overcome the major intrinsic limitations of DTX therapy for
      mCRPC. We evaluated whether reformulation of DTX by facile conjugation to
      carboxymethylcellulose nanoparticles (Cellax) can improve the efficacy and safety
      of the drug in s.c. and bone metastatic models of CRPC. A single dose of the
      nanoparticles completely regressed s.c. PC3 tumor xenografts in mice. In
      addition, Cellax elicited fewer side effects compared to native DTX. Importantly,
      Cellax did not increase the expression of drug resistance molecules in androgen
      independent PC3 prostate cancer cells in comparison with DTX. Lastly, in a bone
      metastatic model of CRPC, Cellax treatment afforded a 2- to 3-fold improvement in
      survival and enhancements in quality-of-life of the animals over DTX and saline
      controls. These results demonstrate the potential of Cellax in improving the
      treatment of mCRPC. 

PMID- 24853463
TI  - pH-Responsive poly(itaconic acid-co-N-vinylpyrrolidone) hydrogels with reduced
      ionic strength loading solutions offer improved oral delivery potential for high
      isoelectric point-exhibiting therapeutic proteins.
AB  - pH-Responsive hydrogels comprised of itaconic acid copolymerized with N
      vinylpyrrolidone (P(IA-co-NVP)) were synthesized and tested as carriers for the
      oral delivery of high isoelectric point (pI) exhibiting therapeutic proteins.
      Swelling studies show that P(IA-co-NVP) hydrogels exhibit significantly greater
      and faster pH-responsive swelling than previously studied methacrylic acid-based
      hydrogels, achieving up to 68% greater equilibrium swelling and 10.4 times
      greater swelling in time-limited experiments. Using salmon calcitonin as a model
      high pI protein therapeutic, we show that P(IA-co-NVP) hydrogels exhibit
      significantly greater delivery potential than methacrylic acid-based hydrogels.
      Additionally, we show that utilizing a lower ionic strength solution during drug
      loading significantly improves drug delivery potential for high pI therapeutics.
      By using a 1.5mM PBS buffer rather than the standard 150 mM PBS buffer during
      loading, up to 83 times as much calcitonin can be delivered in neutral
      conditions, with up to a 9.6-fold improvement in percent release. Using P(IA-co
      NVP) hydrogel microparticles and a low ionic strength loading solution, up to 48
      MUg calcitonin/mg hydrogel can be delivered in small intestinal conditions. Based
      on expected absorption in the small intestine, this is sufficient delivery
      potential for achieving therapeutic dosage via a single, regularly-sized pill
      taken daily.

PMID- 24853464
TI  - Improved gene transfer with histidine-functionalized mesoporous silica
      nanoparticles.
AB  - Mesoporous silica nanoparticles (MSN) were functionalized with
      aminopropyltriethoxysilane (MSN-NH2) then L-histidine (MSN-His) for pDNA delivery
      in cells and in vivo. The complexation of pDNA with MSN-NH2 and MSN-His was first
      studied with gel shift assay. pDNA complexed with MSN-His was better protected
      from DNase degradation than with MSN-NH2. An improvement of the transfection
      efficiency in cells was observed with MSN-His/pDNA compared to MSN-NH2/pDNA,
      which could be explained by a better internalization of MSN-His. The improvement
      of the transfection efficiency with MSN-His was also observed for gene transfer
      in Achilles tendons in vivo.

PMID- 24853465
TI  - Can aggregation of insulin govern its fate in the intestine? Implications for
      oral delivery of the drug.
AB  - The objective of this study is to elucidate the role of low-molecular weight
      biogenic agents, resembling dietary-derived products naturally occurring in the
      intestine, in the regulation of transformations of soluble aggregation-prone
      insulin into aggregates of higher order. In the course of model experiments, a
      striking potential of the amino acids L-arginine (Arg) and L-lysine (Lys) and a
      number of positively charged peptides to induce formation of heterogenic
      supramolecular structures of insulin was demonstrated under environment
      conditions where the protein aggregation in their absence was not observed. This
      phenomenon is assumed to be essential for elaboration of strategies of oral
      delivery of insulin to diabetic patients supplemented by controlling the pH
      values of the intestinal environment where the drug is released.

PMID- 24853466
TI  - Pattern recognition for rapid T2 mapping with stimulated echo compensation.
AB  - Indirect echoes (such as stimulated echoes) are a source of signal contamination
      in multi-echo spin-echo T2 quantification and can lead to T2 overestimation if a
      conventional exponential T2 decay model is assumed. Recently, nonlinear least
      square fitting of a slice-resolved extended phase graph (SEPG) signal model has
      been shown to provide accurate T2 estimates with indirect echo compensation.
      However, the iterative nonlinear least square fitting is computationally
      expensive and the T2 map generation time is long. In this work, we present a
      pattern recognition T2 mapping technique based on the SEPG model that can be
      performed with a single pre-computed dictionary for any arbitrary echo spacing.
      Almost identical T2 and B1 maps were obtained from in vivo data using the
      proposed technique compared to conventional iterative nonlinear least square
      fitting, while the computation time was reduced by more than 14-fold. 

PMID- 24853468
TI  - Regioselectivity in the Cu(I)-catalyzed [4 + 2]-cycloaddition of 2
      nitrosopyridine with unsymmetrical dienes.
AB  - The thermal (uncatalyzed) and Cu(I)-catalyzed reactions of 2-nitrosopyridine
      (PyrNO) with the dienes 1,3-pentadiene, E,E-2,4-hexadienol, and 1-phenylbutadiene
      are investigated experimentally and computationally. The uncatalyzed reactions of
      the first two dienes occur with low regioselectivity, while the latter proceeds
      with complete proximal selectivity. Using the M06/6-311+G(d,p)-SDD method,
      various concerted transition states for the reactions of 2-nitrosopyridine with
      (E)-1,3-pentadiene and 1-phenylbutadiene were computed. In quantitative agreement
      with the experimental findings, (a) no energy difference (0.0 kcal/mol) is found
      between the most stable transition states, endo-prox-anti and endo-dist-anti, in
      the pentadiene/PyrNO reaction, leading to nearly equal amounts of prox and dist
      cycloadducts, and (b) the proximal transition state is strongly favored (by 3.7
      kcal/mol) over the distal for the highly selective phenylbutadiene/PyrNO
      reaction. The regioselectivity of the pentadiene/PyrNO reaction is improved
      markedly (90:10 dist/prox) when catalyzed by Cu(CH3CN)4(+); (diimine)2Cu(+)
      catalysts increase selectivity for the proximal product (55-65%). Modest effects
      of the catalyst nature on regioselectivity are observed in the sorbyl alcohol and
      1-phenylbutadiene reactions. The relative affinity of an equilibrating set of
      (diimine)2Cu(+) complexes for the prox and dist cycloadducts, assessed by ESI-MS,
      is marginally correlated with the prox/dist product regioselectivity produced by
      the corresponding catalysts. Transition states in the Cu(CH3CN)4(+)- and
      Cu(diimine)2(+)-catalyzed reactions are located that account for the observed
      regioselectivities. Coordination effects on the regioselectivity are derived from
      FMO orbital interactions and the extent of electron transfer between the Cu
      center and the coordinated nitroso and diene units. 

PMID- 24853467
TI  - Effect of Gd-EOB-DTPA on hepatic fat quantification using high-speed T2-corrected
      multi-echo acquisition in (1)H MR spectroscopy.
AB  - PURPOSE: To determine whether gadolinium
      ethoxybenzyldiethylenetriaminepentaacetic acid (Gd-EOB-DTPA) administration
      affects hepatic fat quantification by magnetic resonance spectroscopy (MRS) using
      the fast breath-hold high-speed T2-corrected multiecho (HISTO) technique.
      MATERIALS AND METHODS: Seventy-six patients underwent Gd-EOB-DTPA-enhanced liver
      MR and 15sec breath-hold HISTO MRS (4 times), twice before and twice after Gd-EOB
      DTPA administration. Two consecutive MRSs were performed immediately before the
      dynamic study. Post-contrast MRS was performed twice continuously, approximately
      15min after contrast injection, prior to obtaining 20-min hepatobiliary phase
      images. We used paired t-test and intraclass correlation coefficient (ICC) to
      evaluate the variability of the mean fat fraction (FF) on pre-contrast MRS and
      post-contrast MRS and the effect of the contrast agent on the mean FF. RESULTS:
      The mean FFs were not significantly different between pre-contrast MRS and post
      contrast MRS (6.50%+/-6.54 versus 6.70%+/-6.61, P=0.15). The ICC of FF
      calculation between pre- and post-contrast MRS was 0.984. The ICCs for the FF
      magnitude between pre- and post-contrast MRS were 0.452, 0.771, and 0.995 for FF
      <5%, FF 5-10%, and FF >=10%, respectively. CONCLUSION: Gd-EOB-DTPA does not
      appear to influence hepatic fat quantification, especially for patients with
      hepatic steatosis.

PMID- 24853469
TI  - Triple-layered cell sheet for tissue-engineering the synovial membrane of the
      temporomandibular joint.
AB  - OBJECTIVE: Temporomandibular disorder causes the dysfunction of fibroblast-like
      synoviocytes (FLSs) which are predominant in the lining layer (LL) of synovial
      membrane (SM) and responsible for the secretion function of the SM of the
      temporomandibular joint (TMJ). This study aimed to construct a triple-layered
      cell sheet (CS) for tissue-engineering the SM. METHODS: FLSs were harvested and
      identified immunocytochemically. A triple-layered CS was fabricated by an
      original method of combining type I collagen and FLSs. Staining and a
      transmission electron microscope were used to compare the morphological
      similarities between the CS and the natural LL. Hyaluronic acid (HA) production
      and HA synthase 2 (HAS2) gene expression were assessed by ELISA and PCR,
      respectively. Transplantation of triple-layered CSs into nude mice was performed
      and examined by staining and immunohistochemical methods. RESULTS: FLSs expressed
      vimentin, CD44 and heat shock protein 27. The triple-layered CS possessed a
      structure similar to natural LL. No tight conjunction was observed between
      adjacent FLSs. The triple-layered CS secreted HA at a quantity about 3 times that
      of the single-layered CS. The triple-layered structure induced higher expression
      of HAS2 in FLSs. No difference in HAS2 expression between the triple-layered CS
      and natural SM was observed. Multiple-layered FLSs and invasion of host
      fibroblasts and vessels were observed 2 weeks after transplantation. HAS2 and HA
      were expressed in surface cells and extracellular matrix, respectively.
      CONCLUSION: FLSs of the TMJ were type B synoviocytes. The triple-layered CS
      mimicked natural SM morphologically and functionally. The CS survived for 2 weeks
      in vivo. Therefore, triple-layered CS might be highly competent for tissue
      engineered SM.

PMID- 24853470
TI  - Facile fabrication of porous Ni(x)Co(3-x)O4 nanosheets with enhanced
      electrochemical performance as anode materials for Li-ion batteries.
AB  - Herein, we report a novel and facile route for the large-scale fabrication of 2D
      porous NixCo3-xO4 nanosheets, which involves the thermal decomposition of NixCo1
      x hydroxide precursor at 450  degrees C in air for 2 h. The as-prepared 2D porous
      NixCo3-xO4 nanosheets exhibit an enhanced lithium storage capacity and excellent
      cycling stability (1330 mA h g(-1) at a current density of 100 mA g(-1) after 50
      cycles). More importantly, it can render reversible capacity of 844 mA h g(-1),
      even at a high current density of 500 mA g(-1) after 200 cycles, indicating its
      potential applications for high power LIBs. Compared to pure Co3O4, the reduction
      of Co in NixCo3-xO4 is of more significance because of the high cost and toxicity
      of Co. The improved electrochemical performance is attributed to the 2D structure
      and large amounts of mesopores within the nanosheets, which can effectively
      improve structural stability, reduce the diffusion length for lithium ions and
      electrons, and buffer volume expansion during the Li(+) insertion/extraction
      processes. 

PMID- 24853471
TI  - Achieving sustainable plant disease management through evolutionary principles.
AB  - Plants and their pathogens are engaged in continuous evolutionary battles and
      sustainable disease management requires novel systems to create environments
      conducive for short-term and long-term disease control. In this opinion article,
      we argue that knowledge of the fundamental factors that drive host-pathogen
      coevolution in wild systems can provide new insights into disease development in
      agriculture. Such evolutionary principles can be used to guide the formulation of
      sustainable disease management strategies which can minimize disease epidemics
      while simultaneously reducing pressure on pathogens to evolve increased
      infectivity and aggressiveness. To ensure agricultural sustainability, disease
      management programs that reflect the dynamism of pathogen population structure
      are essential and evolutionary biologists should play an increasing role in their
      design. 

PMID- 24853472
TI  - Role of nanoparticles in controlling arsenic mobilization from sediments near a
      realgar tailing.
AB  - Microcosm experiments were conducted to investigate the mechanism of microbial
      mediated As mobilization from high arsenic tailing sediments amended with
      nanoparticles (NPs). The addition of SiO2 NPs could substantially stimulate
      arsenic mobilization in the sodium acetate amendment sediments. However, the
      addition of Fe2O3 and Fe3O4 NPs restrained arsenic release because these NPs
      resulted in Fe-As coprecipiate. Moreover, NP additions in sediments amended with
      sodium acetate as the electron donor clearly promoted microbial dissimilatory
      iron reduction. Nearly 4 times the Fe(II) (11.67-12.87 mg.L(-1)) from sediments
      amended with NPs and sodium acetate was released compared to sediments amended
      with only sodium acetate (3.49 mg.L(-1)). Based on molecular fingerprinting and
      sequencing analyses, the NP additions could potentially change the sediment
      bacterial community composition and increase the abundance of Fe(III) and As(V)
      reduction bacteria. Several potential NP-stimulated bacteria were related to
      Geobacter, Anaeromyxobacter, Clostridium, and Alicyclobacillus. The findings
      offer a relatively comprehensive assessment of NP (e.g., Fe2O3, Fe3O4, and SiO2)
      effects on sediment bacterial communities and As mobilization. 

PMID- 24853473
TI  - Re-appraisal of risk classifications for primary gastrointestinal stromal tumors
      (GISTs) after complete resection: indications for adjuvant therapy.
AB  - BACKGROUND: A substantial number of localized gastrointestinal stromal tumor
      (GIST) patients have recurrences even after complete resection. The risk of
      recurrence after complete resection should be estimated when considering adjuvant
      therapy. In this study, we evaluated prognostic factors of GIST recurrence and
      compared several reported risk-stratification schemes for defining risk of
      recurrence to guide the use of adjuvant therapy using data from a large Japanese
      GIST population. METHODS: We analyzed clinicopathological data collected
      retrospectively and prospectively from 712 GISTs with complete resection from
      1980-2010. We evaluated possible prognostic factors and compared the National
      Institutes of Health consensus criteria, the Armed Forces Institute of Pathology
      criteria, Joensuu's modified NIH classification (J-NIHC), the American Joint
      Committee on Cancer staging system (AJCCS), and the Japanese modified NIH
      criteria for prediction of tumor recurrence in adjuvant settings. RESULTS:
      Univariate analysis suggested that the following factors were prognostic: tumor
      size, mitotic count, site, clinically malignant features of rupture and/or
      invasion, and gender. In multivariate analysis, size >5 cm, mitotic count >5/50
      HPF, non-gastric location, and the presence of rupture and/or macroscopic
      invasion were independent adverse prognostic factors. When adjuvant therapy is
      considered for patients with high-risk GIST, the J-NIHC was the most sensitive
      classification system, while the AJCCS appeared to be the most accurate for
      predicting recurrence. CONCLUSION: Tumor size, mitotic count, tumor site, and
      clinical features of rupture and/or invasion were important prognostic factors
      for GIST recurrence. Joensuu's classification appeared to best identify
      candidates for adjuvant therapy.

PMID- 24853474
TI  - Protease and phospholipase activities of Candida spp. isolated from cutaneous
      candidiasis.
AB  - BACKGROUND: Cases of superficial and invasive mycoses caused by emerging species
      of Candida have been increasingly reported over the last thirty years. The
      production of hydrolytic enzymes plays a central role in the fungal infective
      process. In Candida infections the secretion of both proteases and phospholipases
      are well-known virulence attributes. AIMS: To determine the protease and
      phospholipase production from 58 human clinical isolates of Candida obtained from
      individuals with cutaneous candidiasis seen in the Human and Veterinary
      Diagnostic Mycology Sector from Universidade Federal Fluminense (UFF), Brazil,
      from November 2008 to August 2009. METHODS: Fungal identification was performed
      using biochemical tests. Proteolytic activity was detected on agar plates
      containing bovine serum albumin, and phospholipase production was determined on
      egg-yolk plates. RESULTS: The Candida species isolated were Candida parapsilosis
      (27.59%), Candida famata (18.96%), Candida albicans (15.52%), Candida haemulonii
      (12.06%), Candida ciferri (8.62%), Candida guilliermondii (6.90%), Candida
      tropicalis (5.17%) and Candida lipolytica (5.17%). All isolates of C. albicans
      produced both protease and phospholipase. As regards the isolates of non-C.
      albicans Candida species, 53.06% and 4.08% were able to produce protease and
      phospholipase, respectively. For example, the majority of isolates of C.
      parapsilosis (15/16) produced protease, while 40% of C. ciferri isolates (2/5)
      were phospholipase producers. This study shows, for the first time, that C.
      ciferri and C. haemulonii strains were able to produce protease. CONCLUSIONS:
      Collectively, our results showed that different species of Candida isolated from
      cutaneous lesions were able to produce proteases and/or phospholipases, which are
      multifunctional molecules directly involved in the infectious process of these
      fungi.

PMID- 24853475
TI  - Agronomic conditions and crop evolution in ancient Near East agriculture.
AB  - The appearance of agriculture in the Fertile Crescent propelled the development
      of Western civilization. Here we investigate the evolution of agronomic
      conditions in this region by reconstructing cereal kernel weight and using stable
      carbon and nitrogen isotope signatures of kernels and charcoal from a set of 11
      Upper Mesopotamia archaeological sites, with chronologies spanning from the onset
      of agriculture to the turn of the era. We show that water availability for crops,
      inferred from carbon isotope discrimination (Delta(13)C), was two- to fourfold
      higher in the past than at present, with a maximum between 10,000 and 8,000 cal
      BP. Nitrogen isotope composition (delta(15)N) decreased over time, which suggests
      cultivation occurring under gradually less-fertile soil conditions. Domesticated
      cereals showed a progressive increase in kernel weight over several millennia
      following domestication. Our results provide a first comprehensive view of
      agricultural evolution in the Near East inferred directly from archaeobotanical
      remains.

PMID- 24853476
TI  - Self-assembled monolayers of cholesterol and cholesteryl esters on graphite.
AB  - The molecular arrangements of self-assembled monolayers (SAMs) of cholesterol,
      cholesteryl laurate, and cholesteryl stearate adsorbed on a graphite surface were
      studied using scanning tunneling microscopy (STM) at the liquid-solid interface.
      The STM images of the SAMs showed two-dimensional periodic arrays of bright
      regions that corresponded to the sterol rings. However, individual sterol rings
      could not be observed in the bright regions in the STM images of the cholesterol
      monolayers. Nevertheless, by comparing the STM images and the crystallographic
      data, it is concluded that the cholesterol molecules are arranged in pairs
      oriented head-to-head owing to the hydrogen bonds between the hydroxyl groups.
      These dimers, in turn, are oriented parallel to each other, owing to the
      interactions between the sterol rings. The STM images of cholesteryl ester
      monolayers had molecular resolution and showed pairs of cholesteryl ester
      molecules oriented in an antiparallel manner, with their fatty acid chains
      located in the central regions. Furthermore, the fatty acid chains of cholesteryl
      stearate were observed to be oriented in the (1120) zigzag direction of the
      graphite lattice, whereas those of cholesteryl laurate were oriented in the
      (1010) armchair direction. These observations reveal that the interactions
      between the fatty acid chains affect the structure of the SAMs. The molecular
      arrangements also depend on the lengths of the fatty acid chains of the
      cholesterol esters and hence on the interactions between the alkyl chains and the
      graphite surface. The self-assembly at the liquid-solid interface is therefore
      controlled by the interactions between sterol rings, between alkyl chains, and
      between alkyl chains and the substrate.

PMID- 24853478
TI  - Gold-catalyzed C(sp3)-H bond functionalization.
AB  - C-H bonds are ubiquitous in organic molecules. Homogenous gold-catalyzed direct
      functionalization of unsaturated C-H bonds has emerged as a powerful method in
      our synthetic toolbox. However, Csp(3)-H bonds have larger dissociation energy
      and lower proton acidity, and thus the efficient and exquisitely selective
      cleavage of this kind of chemical bonds for the formation of new carbon-carbon
      and carbon-heteroatom bonds is still a great challenge. In this tutorial review,
      we will highlight the recent achievements of gold-catalyzed oxidative and redox
      neutral Csp(3)-H bond functionalization, which opens new avenues for economical
      and sustainable construction of fine chemicals. 

PMID- 24853477
TI  - Osteogenic differentiation of umbilical cord and adipose derived stem cells onto
      highly porous 45S5 Bioglass(r)-based scaffolds.
AB  - In the context of bone tissue engineering (BTE), combinations of bioactive
      scaffolds with living cells are investigated to optimally yield functional bone
      tissue for implantation purposes. Bioactive glasses are a class of highly
      bioactive, inorganic materials with broad application potential in BTE
      strategies. The aim of this study was to evaluate bioactive glass (45S5
      Bioglass((r))) samples of composition: 45 SiO2, 24.5 CaO, 24.5 Na2O, and 6 P2O5
      (in wt%) as scaffold materials for mesenchymal stem cells (MSC). Pore
      architecture of the scaffolds as well as cell behavior in the three-dimensional
      environment was evaluated by several methods. Investigations concerned the
      osteogenic cell attachment, growth and differentiation of adipose tissue derived
      MSC (adMSC) compared with MSC from human full term umbilical cord tissues (ucMSC)
      on porous Bioglass((r))-based scaffolds over a cultivation period of 5 weeks.
      Differences in lineage-specific osteogenic differentiation of adMSC and ucMSC on
      Bioglass((r)) samples were demonstrated. The investigation led to positive
      results in terms of cell attachment, proliferation, and differentiation of MSC
      onto Bioglass((r))-based scaffolds confirming the relevance of these matrices for
      BTE applications.

PMID- 24853479
TI  - Ultrahigh performance C60 nanorod large area flexible photoconductor devices via
      ultralow organic and inorganic photodoping.
AB  - One dimensional single-crystal nanorods of C60 possess unique optoelectronic
      properties including high electron mobility, high photosensitivity and an
      excellent electron accepting nature. In addition, their rapid large scale
      synthesis at room temperature makes these organic semiconducting nanorods highly
      attractive for advanced optoelectronic device applications. Here, we report low
      cost large-area flexible photoconductor devices fabricated using C60 nanorods. We
      demonstrate that the photosensitivity of the C60 nanorods can be enhanced ~400
      fold via an ultralow photodoping mechanism. The photodoped devices offer
      broadband UV-vis-NIR spectral tuneability, exhibit a detectivitiy>10(9) Jones, an
      external quantum efficiency of ~100%, a linear dynamic range of 80 dB, a rise
      time 60 us and the ability to measure ac signals up to ~250 kHz. These figures of
      merit combined are among the highest reported for one dimensional organic and
      inorganic large-area planar photoconductors and are competitive with commercially
      available inorganic photoconductors and photoconductive cells. With the
      additional processing benefits providing compatibility with large-area flexible
      platforms, these devices represent significant advances and make C60 nanorods a
      promising candidate for advanced photodetector technologies.

PMID- 24853480
TI  - Designing processive catalytic systems. Threading polymers through a flexible
      macrocycle ring.
AB  - The translocation of polymers through pores is widely observed in nature and
      studying their mechanism may help understand the fundamental features of these
      processes. We describe here the mechanism of threading of a series of polymers
      through a flexible macrocyclic ring. Detailed kinetic studies show that the
      translocation speed is slower than the translocation speed through previously
      described more rigid macrocycles, most likely as a result of the wrapping of the
      macrocycle around the polymer chain. Temperature-dependent studies reveal that
      the threading rate increases on decreasing the temperature, resulting in a
      negative activation enthalpy of threading. The latter is related to the opening
      of the cavity of the macrocycle at lower temperatures, which facilitates binding.
      The translocation process along the polymer chain, on the other hand, is
      enthalpically unfavorable, which can be ascribed to the release of the tight
      binding of the macrocycle to the chain upon translocation. The combined kinetic
      and thermodynamic data are analyzed with our previously proposed consecutive
      hopping model of threading. Our findings provide valuable insight into the
      translocation mechanism of macrocycles on polymers, which is of interest for the
      development of processive catalysts, i.e., catalysts that thread onto polymers
      and move along it while performing a catalytic action. 

PMID- 24853481
TI  - Evidence for the C-seal device remains inconclusive.

PMID- 24853482
TI  - Acute lower gastrointestinal bleeding originating from an arteriovenous fistula
      of superior rectal artery.

PMID- 24853483
TI  - Dental arch relationship outcomes in one- and two-stage palatoplasty for Japanese
      patients with complete unilateral cleft lip and palate.
AB  - OBJECTIVE: To compare dental arch relationship outcomes following one- and two
      stage palatal repair. DESIGN: Nonrandomized, clinical trial with concurrent
      control. SETTING: Hokkaido University Hospital. PATIENTS: Sixty-eight
      consecutively treated Japanese patients with complete unilateral cleft lip and
      palate. INTERVENTIONS: Thirty-one of the 68 patients underwent two-stage
      palatoplasty with delayed hard palate closure, and 37 patients underwent one
      stage pushback palatoplasty. MAIN OUTCOME MEASURES: Dental casts were taken at
      4.9 to 6.3 (mean: 5.2) years of age in the two-stage group and at 4.0 to 6.3
      (mean: 5.1) years of age in the one-stage group, and dental arch relationships
      were assessed using the 5-Year-Olds' Index (5-Y) by four raters and the
      Huddart/Bodenham Index (HB) by two raters. RESULTS: Intrarater and interrater
      reliabilities evaluated using weighted kappa statistics were good or better for
      the 5-Y and HB ratings. The mean 5-Y score was 2.94 in the two-stage group and
      3.13 in the one-stage group (P value was not significant). However, there was a
      significant difference in distributions between the groups (P < .05). The HB
      scores of molars were significantly greater in the two-stage group than in the
      one-stage group (P < .05). The rank correlation coefficients between the 5-Y and
      total HB score (rho = -0.840, P < .01) and between the 5-Y and the score of the
      incisors in the HB (rho = -0.814, P < .01) were significantly increased.
      CONCLUSIONS: These results suggest that the anteroposterior relationship was not
      significantly different between the groups, but the transversal relationship was
      better in the two-stage group than in the one-stage group.

PMID- 24853484
TI  - Older adults' experiences of living with cleft lip and palate: a qualitative
      study exploring aging and appearance.
AB  - Objective : To explore older adults' experiences of living with cleft lip and/or
      palate (CL/P), focusing on aging and appearance. Design : An exploratory
      descriptive qualitative study. Participants : Individual semi-structured
      interviews (five via telephone, one face-to-face) conducted with six adults
      between the ages of 57 and 82 years. Results : Interview transcripts were
      analyzed using interpretative phenomenological analysis, which resulted in five
      themes: cleft across the life span, keeping up appearances, being one of a kind,
      resilience and protection, and cleft in an ever-changing society. A CL/P had an
      ongoing impact on participants' lives, although its relevance shifted over time
      and some aspects of life (e.g., romantic relationships, decisions about having
      children of their own) were particularly affected. Participants seemed at ease
      living with CL/P as an older adult and considered it an important aspect of their
      identity, yet they still described feeling isolated at times and had little
      contact with other people with a cleft. They felt that health care could be more
      considerate to the needs of older people with a cleft, particularly around
      dentistry and information provision. Participants thought societal attitudes
      toward visible differences had changed over the years, but not necessarily for
      the better. A paradox was evident between reports of being noticed by others
      because of their cleft and simultaneously feeling invisible or ignored because of
      their age. Conclusions : These findings have implications for provision of care
      for older adults with a CL/P and for younger people with a CL/P who will be the
      older generation of the future. 

PMID- 24853485
TI  - Influence of primary diagnosis and complications on visual outcome in patients
      receiving a Boston type 1 keratoprosthesis.
AB  - PURPOSE: To analyse how primary diagnosis and complications affect the evolution
      of post-operative visual acuity (VA). METHODS: We performed retrospective chart
      analysis on 59 eyes in 57 patients with various diagnoses, most of which were non
      standard indications for Boston type 1 keratoprosthesis (Kpro) implantation. The
      follow-up period was at least 3 months. Patients were classified based on the
      evolution of post-operative VA: group A demonstrated stable VA improvement, group
      B lost VA improvement and group C no significant VA improvement. RESULTS: We
      assigned 46% of our cases to group A with stable VA improvement, 32% to group B
      with lost VA improvement, and 22% to group C with no VA improvement. The number
      of graft failures before Kpro implantation did not influence VA outcome. Except
      for the relatively good VA outcome in chemical burn and radiation injury
      patients, there seems to be no association between primary diagnosis and positive
      or negative VA outcome. Only 9% of patients with posterior segment complications
      and 20% with infections and associated pathologies were assigned to group A.
      CONCLUSION: Most cases (78%) showed improvement in VA after Boston type 1 Kpro
      (groups A and B). Posterior segment complications and infections mostly resulted
      in persistent loss of vision. These complications should be prevented and
      carefully treated.

PMID- 24853486
TI  - A computational framework for simulation of the delivery of substances into
      cells.
AB  - In this paper, we propose a simple computational framework for the rapid
      simulation of the delivery of substances into cells. Our approach treats the
      substances and the cell membrane as a collection of particles forming a discrete
      dynamical system, which is described by Newtonian equations in a purely
      mechanistic way. Detailed aspects about the modeling of particle interactions are
      discussed and resolved. The main advantage of such an approach is that it can
      offer a good qualitative picture of the delivery mechanism without the need to
      resort to detailed descriptions of the complex intermolecular interactions that
      are observed at small scales of the cell membrane. A numerical time integration
      scheme is formulated for solution of the system dynamics, and examples of
      simulations are provided. Computational particle-based models render reliable and
      fast simulation tools. We believe they can be very useful to help advance the
      design of delivery systems.

PMID- 24853487
TI  - Salvianolic acid A suppresses CCL-20 expression in TNF-alpha-treated macrophages
      and ApoE-deficient mice.
AB  - OBJECTIVES: The CC chemokine ligand-20 (CCL-20)/macrophage inflammatory protein
      3alpha has been seen as one of the most important chemokines and played a key
      role in atherogenesis, but the mechanism that underlies the regulation of CCL-20
      has not been established clearly yet. The aim of this study was to investigate
      the influence of salvianolic acid A (SAA) on the expression of CCL-20 in
      macrophages and ApoE-deficient (ApoE) mice. METHODS: The expression of CCL-20 was
      detected both at protein and messenger RNA levels in RAW264.7 cells. We validated
      the result in ApoE mice that were intraperitoneally injected with SAA.
      Phosphorylation of p38 mitogen-activated protein kinase was detected with Western
      blot, and inhibitor of p38 was used to investigate the mechanism of regulation of
      CCL-20. Hematoxylin and eosin and Oil-Red-O staining were used to evaluate the
      atherosclerotic lesions and lipid accumulation in ApoE mice. Immunohistochemical
      analysis was used to detect the expressions of CCL-20 and CCR6 in the
      atherosclerotic lesions. Immunofluorescent analysis was used to certify the
      origination of CCL-20. RESULTS: Recombinant tumor necrosis factor-alpha (TNF
      alpha) upregulated CCL-20 production in dose- and time-dependent manners in
      RAW264.7 cells. The activity of TNF-alpha-induced CCL-20 production seemed to be
      significantly suppressed by SAA. Using p38 mitogen-activated protein kinase
      inhibitor, we found that p38 mediated the effects of TNF-alpha- and SAA-induced
      CCL-20 expression changes. In addition, immunohistochemical analysis of aortic
      root of ApoE mice also demonstrated that the expressions of CCL-20 and CCR6 were
      both downregulated significantly with SAA treatment. Furthermore, treatment of
      SAA inhibited the progression of the atherosclerotic plaques and lipid
      accumulation. CONCLUSIONS: These results demonstrate that TNF-alpha increased but
      SAA suppressed CCL-20 production significantly via a novel mechanism.

PMID- 24853488
TI  - Curcuma oil reduces endothelial cell-mediated inflammation in postmyocardial
      ischemia/reperfusion in rats.
AB  - Endothelial cells initiated inflammation persisting in postmyocardial infarction
      needs to be controlled and moderated for avoiding fatal complications. Curcuma
      oil (C.oil, Herbal Medicament), a standardized hexane soluble fraction of Curcuma
      longa has possessed neuroprotective effect. However, its effect on myocardial
      ischemia/reperfusion (MI/RP) and endothelial cells remains incompletely defined.
      Here, using in vivo rat MI/RP injury model and in vitro cellular approaches using
      EA.hy926 endothelial cells, enzyme-linked immunosorbent assay, real-time
      polymerase chain reaction, and myograph, we provide evidence that with effective
      regimen and preconditioning of rats with C.oil (250 mg/kg, PO), before and after
      MI/RP surgery protects rats from MI/RP-induced injury. C.oil treatment reduces
      left ventricular ischemic area and endothelial cell-induced inflammation,
      specifically in the ischemic region (*P < 0.0001) and improved endothelial
      function by reducing the expression of proinflammatory genes and adhesion factors
      on endothelial cells both in vitro and in vivo. Furthermore, mechanistic studies
      have revealed that C.oil reduced the expression of adhesion factors like E
      selectin (#P = 0.0016) and ICAM-1 ($P = 0.0069) in initiating endothelial cells
      induced inflammation. In line to the real-time polymerase chain reaction
      expression data, C.oil reduced the adhesion of inflammatory cells to endothelial
      cells as assessed by the interaction of THP-1 monocytes with the endothelial
      cells using flow-based adhesion and under inflammatory conditions. These studies
      provide evidence that salutary effect of C.oil on MI/RP could be achieved with
      pretreatment and posttreatment of rats, C.oil reduced MI/RP-induced injury by
      reducing the endothelial cell-mediated inflammation, specifically in the ischemic
      zone of MI/RP rat heart.

PMID- 24853490
TI  - Obstetrical and neonatal outcomes following unsuccessful external cephalic
      version: a stratified analysis amongst failures, successes, and controls.
AB  - OBJECTIVE: Though on average one out of every two external cephalic versions
      (ECV) fails to rotate the breech fetus, little is known about the outcomes of
      pregnancies in which ECV is unsuccessful. The objective of the present study is
      to compare obstetrical and neonatal outcomes following failure of ECV, relative
      to cases of breech controls without an attempt at ECV. STUDY DESIGN: We conducted
      a retrospective, population-based, cohort study using the CDC's Birth Data files
      from the US for the year 2006. We stratified the cohort according to fetal
      presentation and ECV status: success, failure, and no ECV (controls). The effect
      of failure of ECV on the risk of several neonatal and obstetrical outcomes was
      estimated using logistic regression analysis, adjusting for relevant confounders.
      RESULTS: We analyzed a total of 4 273 225 births, out of which 183 323 (4.3%) met
      inclusion criteria. Relative to breech controls, failed ECV occurred more
      frequently amongst Caucasian, college-educated, married women bearing a female
      fetus. Compared to no ECV, failure of ECV was associated with increased odds of
      PROM (aOR, 1.75; 95% CI, 1.60-1.90), elective cesarean delivery (aOR, 1.53; 95%
      CI, 1.36-1.72), cesarean delivery in labor (aOR, 1.38; 95% CI, 1.21-1.57),
      abnormal fetal heart tracing (aOR, 1.78; 95% CI, 1.50-2.11), assisted ventilation
      at birth (aOR, 1.50; 95% CI, 1.27-1.78), 5-min APGAR scores <7 (aOR, 1.35; 95%
      CI, 1.20-1.51), and NICU admission (aOR, 1.48; 95% CI, 1.20-1.82). The delayed
      spontaneous fetal restitution rate was 13%. When stratifying controls with
      regards to trial of labor status, the increased risk of failed ECV persisted for
      cesarean delivery, NICU admission, assisted ventilation and abnormal fetal
      tracing, independently of whether a trial of labor took place. CONCLUSION:
      Relative to breech controls without attempt at ECV, failure of ECV to restitute
      cephalic presentation appears to be associated with an increased risk of adverse
      perinatal and obstetrical outcomes.

PMID- 24853489
TI  - Gene and microRNA transcriptional signatures of angiotensin II in endothelial
      cells.
AB  - Growth of atherosclerotic plaque requires neovascularization (angiogenesis). To
      elucidate the involvement of angiotensin II (Ang II) in angiogenesis, we
      performed gene microarray and microRNA (miRNA) polymerase chain reaction array
      analyses on human coronary artery endothelial cells exposed to moderate
      concentration of Ang II for 2 and 12 hours. At 12, but not 2, hours, cultures
      treated with Ang II exhibited shifts in transcriptional activity involving 267
      genes (>1.5-fold difference; P < 0.05). Resulting transcriptome was most
      significantly enriched for genes associated with blood vessel development,
      angiogenesis, and regulation of proliferation. Majority of upregulated genes
      implicated in angiogenesis shared a commonality of being either regulators (HES1,
      IL-18, and CXCR4) or targets (ADM, ANPEP, HES1, KIT, NOTCH4, PGF, and SOX18) of
      STAT3. In line with these findings, STAT3 inhibition attenuated Ang II-dependent
      stimulation of tube formation in Matrigel assay. Expression analysis of miRNAs
      transcripts revealed that the pattern of differential expression for miRNAs was
      largely consistent with proangiogenic response with a prominent theme of
      upregulation of miRs targeting PTEN (miR-19b-3p, miR-21-5p, 23b-3p, and 24-3p),
      many of which are directly or indirectly STAT3 dependent. We conclude that STAT3
      signaling may be an intrinsic part of Ang II-mediated proangiogenic response in
      human endothelial cells.

PMID- 24853491
TI  - The impact of platelet functions and inflammatory status on the severity of
      preeclampsia.
AB  - OBJECTIVE: To find out whether there is a correlation between the extent of
      platelet activation and inflammation and the severity of preeclampsia (PE) in the
      third trimester of pregnancy. METHODS: Forty-one women with PE (n = 23 severe, n
      = 18 mild) and 80 normotensive pregnant (NP) women were included in the study.
      Their blood samples were obtained and interleukin (IL)-8 and IL-10 levels
      measured by an enzyme-linked immunosorbent assay. Basal CD61 and CD62P
      expressions on CD41-positive platelets were analyzed with the use of flow
      cytometry. Platelet aggregation was induced by adenosine diphosphate and
      determined by aggregometry. RESULTS: CD62P expression was increased in severely
      preeclamptic women, and the platelet aggregation was decreased in both mildly and
      severely preeclamptic women in comparison with NP women. However, CD61 expression
      was similar among the groups. An enhanced inflammatory response was seen in
      severely preeclamptic women demonstrated by increased levels of IL-8 and
      decreased levels of IL-10. However, the intensity of platelet activation did not
      correlate directly with the change in plasma levels of IL-8 and IL-10 in
      preeclamptic women. CONCLUSIONS: Platelets may have a role in the inflammatory
      response in PE. However, the severity of inflammation is found to be independent
      from the intensity of platelet activation in preeclamptic women. This seems to be
      related to mechanisms causing alterations of cytokine levels such as IL-8 and IL
      10, rather than platelet activation.

PMID- 24853492
TI  - Factor affecting length of stay in late preterm infants: an US national database
      study.
AB  - OBJECTIVES: Late preterm infants are the fastest growing segment of the premature
      infant population in the United States. However, it is not known if demographic
      and clinical factors can impact the length of hospital stay (LOS) in this
      population. The objectives of this study are to determine the following: (a)
      factors associated with a LOS > 3 d and (b) whether there is any difference in
      risks between infants born at 33-34 versus 35-36 weeks. METHODS: Utilizing the
      Nationwide Inpatient Sample Database, a de-identified dataset produced by the
      Healthcare Cost and Utilization Project, analysis of 81 913 infants born at 33-36
      weeks from 2007 to 2008 was conducted. LOS outcome was defined as <=3 and >3 d.
      Bivariable and multivariable logistic regression was used to evaluate predictors
      of LOS among this population. RESULTS: Only 42.7% of infants were discharged home
      within three days. Factors associated with a LOS > 3 d included gestational age
      of <35 weeks (RR = 1.63; CI: 1.58-1.68), birth weight of < 2500 g (RR = 1.36; CI:
      1.33-1.39), male sex (RR = 1.06; CI: 1.05-1.07), delivery via C-section (RR =
      1.46; CI: 1.41-1.51) and multiple gestation (RR = 1.08; 95% CI: 1.06-1.09). Other
      significant factors included race, birth region, primary insurance payer and
      clinical complications. In the adjusted interaction model, these variables have
      more impact on longer LOS in the 35-36 weeks group (p < 0.0001). CONCLUSION:
      Birth region in addition to gestational age, birth weight, gender, mode of
      delivery, multiple gestation and primary insurance payer affect LOS in late
      preterm infants. These variables are more critical for the 35-36 week population.

PMID- 24853493
TI  - Synthesis, xanthine oxidase inhibition, and antioxidant screening of benzophenone
      tagged thiazolidinone analogs.
AB  - A series of novel 2-(diaryl methanone)-N-(4-oxo-2-phenyl-thiazolidin-3-yl)
      acetamides were synthesized by various Schiff bases of (4-benzoyl-phenoxy)-aceto
      hydrazide with thioglycolic acid. The structures of the newly synthesized
      compounds were confirmed by IR, (1) H NMR, mass spectra, and C, H, N analysis.
      Further, all the synthesized compounds 9a-n were evaluated for xanthine oxidase
      (XO) inhibition and antioxidant properties. Among all the tested compounds, 9f,
      9m, and 9n demonstrated potent XO inhibition of 52, 76, and 26%, respectively,
      compared to the standard drug allopurinol, which is evident from in vitro and in
      silico analysis. On the other hand, compounds 9c, 9d, and 9k exhibit potent
      antioxidant properties. 

PMID- 24853494
TI  - Enhanced charge-discharge properties of SnO2 nanocrystallites in confined carbon
      nanospace.
AB  - Almost perfect embedding of SnO2 nanocrystallites in carbon nanopores was
      achieved by in situ synthesis using vaporized SnCl2 and silica opal-derived
      nanoporous carbons. The reversibility of SnO2-Sn conversion and Sn-Li alloying/de
      alloying reactions was greatly enhanced by the confinement in regulated carbon
      nanospace. 

PMID- 24853495
TI  - Evolution of protein interactions: from interactomes to interfaces.
AB  - Protein-protein interactions lie at the heart of most cellular processes. Many
      experimental and computational studies aim to deepen our understanding of these
      interactions and improve our capacity to predict them. In this respect, the
      evolutionary perspective is most interesting, since the preservation of structure
      and function puts constraints on the evolution of proteins and their
      interactions. However, uncovering these constraints remains a challenge, and the
      description and detection of evolutionary signals in protein-protein interactions
      is currently a very active field of research. Here, we review recent works
      dissecting the mechanisms of protein-protein interaction evolution and exploring
      how to use evolutionary information to predict interactions, both at the global
      level of the interactome and at the detailed level of protein-protein interfaces.
      We first present to what extent protein-protein interactions are found to be
      conserved within interactomes and which properties can influence their
      conservation. We then discuss the evolutionary and co-evolutionary pressures
      applied on protein-protein interfaces. Finally, we describe how the computational
      prediction of interfaces can benefit from evolutionary inputs.

PMID- 24853496
TI  - Overview of substance use and treatment from Australia.
AB  - This paper aims to provide an overview of drug and alcohol issues and their
      management in Australia. Overall, Australia has good health relative to the
      United States and other similar nations and generally similar rates of substance
      use disorders. A whole-of-government strategic approach has been developed for
      managing drug and alcohol problems, with a National Drug Strategy that has
      adopted a pragmatic approach to substance use problems through 3 "pillars"-
      demand, supply, and harm reduction. This approach has been attributed to
      Australia's remarkably low human immunodeficiency virus (HIV) prevalence among
      people who inject drugs (<2%). Most community primary health care is provided
      through Australia's universal health care scheme, which provides a rebate for
      nearly all medical services according to a scheduled fee. Inpatient and
      outpatient care, including drug and alcohol services, delivered at public
      hospitals are currently provided with no patient co-payments. The health of
      Australia's first peoples, Australian Aboriginals and Torres Strait Islanders,
      remains challenging primarily due to the transgenerational impacts of
      dispossession, social and economic disadvantage, and some cultural differences.
      Although substance use is a key issue for Australian Aboriginals, there are
      currently insufficient dedicated drug and alcohol services for this group.
      Notwithstanding this important exception, Australia's health and substance use is
      favorable relative to other developed nations, offering universal health care and
      a pragmatic drug and alcohol strategy.

PMID- 24853497
TI  - Improved model to predict the free energy contribution of trinucleotide bulges to
      RNA duplex stability.
AB  - Trinucleotide bulges in RNA commonly occur in nature. Yet, little data exists
      concerning the thermodynamic parameters of this motif. Algorithms that predict
      RNA secondary structure from sequence currently attribute a constant free energy
      value of 3.2 kcal/mol to all trinucleotide bulges, regardless of bulge sequence.
      To test the accuracy of this model, RNA duplexes that contain frequent naturally
      occurring trinucleotide bulges were optically melted, and their thermodynamic
      parameters-enthalpy, entropy, free energy, and melting temperature-were
      determined. The thermodynamic data were used to derive a new model to predict the
      free energy contribution of trinucleotide bulges to RNA duplex stability: DeltaG
      degrees 37, trint bulge = DeltaG degrees 37, bulge + DeltaG degrees 37, AU +
      DeltaG degrees 37, GU. The parameter DeltaG degrees 37, bulge is variable
      depending upon the purine and pyrimidine composition of the bulge, DeltaG degrees
      37, AU is a 0.49 kcal/mol penalty for an A-U closing pair, and DeltaG degrees 
      37, GU is a -0.56 kcal/mol bonus for a G-U closing pair. With both closing pair
      and bulge sequence taken into account, this new model predicts free energy values
      within 0.30 kcal/mol of the experimental value. The new model can be used by
      algorithms that predict RNA free energies as well as algorithms that use free
      energy minimization to predict RNA secondary structure from sequence. 

PMID- 24853498
TI  - Biventricular pacing cardiac contractility modulation improves cardiac
      contractile function via upregulating SERCA2 and miR-133 in a rabbit model of
      congestive heart failure.
AB  - OBJECTIVE: To compare the effects of biventricular electrical pacing and
      conventional single-ventricular pacing for cardiac contractility modulation (CCM)
      on cardiac contractile function and to delineate the underlying molecular
      mechanisms. METHODS: Forty rabbits were divided into four groups before surgery:
      healthy control, HF sham, HF left ventricular pacing CCM (LVP-CCM), and HF
      biventricular pacing CCM (BVP-CCM) groups with n=10 for each group. A rabbit
      model of chronic heart failure was established by ligating ascending aortic root
      of rabbits. Then electrical stimulations during the absolute refractory period
      were delivered to the anterior wall of left ventricle in the LVP-CCM group and on
      the anterior wall of both left and right ventricles in the BVP-CCM group lasting
      six hours per day for seven days. Changes in ventricular structure, cardiac
      function and electrocardiogram were monitored before and after CCM stimulation.
      RESULTS: Compared with the sham-operated group, heart weight, heart weight index,
      LV end-systolic diameter (LVESD), LV end-diastolic diameter (LVEDD) in the LVP
      CCM and BVP-CCM groups were significantly decreased (p<0.05), while LV ejection
      fraction (LVEF) and fractional shortening fraction (FS) were increased (p<0.05).
      Notably all these changes were consistently found to be greater in BVP-CCM than
      in LVP-CCM. Moreover, plasma BNP levels were highest in the HF sham-control
      group, followed by the LVP-CCM group, and lowest in the BVP-CCM group (p<0.05).
      Furthermore, sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA2a) protein levels
      were upregulated by 1.7 and 2.4 fold, along with simultaneous upregulation of a
      cardiac-enriched microRNA miR-133 levels by 2.6 and 3.3 fold, in LVP-CCM and BVP
      CCM, respectively, compared to sham. CONCLUSIONS: Biventricular pacing CCM is
      superior to conventional monoventricular pacing CCM, producing greater
      improvement cardiac contractile function. Greater upregulation of SERCA2 and miR
      133 may account, at least partially, for the improvement by BVP-CCM.

PMID- 24853499
TI  - Impact of HLA-B*35 subtype differences on HIV disease outcome in Mexico.
AB  - HLA-B35 has consistently been associated with rapid HIV disease progression,
      particularly alleles of the Px group. As B35 is the most prevalent HLA-B in
      Mexico, we investigated HIV disease outcome in relation to HLA expression in a
      large cohort (n=976) of Mexicans. Contrary to the previous studies, no impact on
      viral load or CD4 cell count was observed in association with the B35 PY/Px
      groups. However, we observed differences in HIV disease outcome associated with
      specific HLA-B35 alleles.

PMID- 24853500
TI  - Ultrastructural observation of mesophyll cells and temporal expression profiles
      of the genes involved in transitory starch metabolism in flag leaves of wheat
      after anthesis.
AB  - Transitory starch in cereal plant leaves is synthesized during the day and
      remobilized at night to provide a carbon source for growth and grain filling, but
      its mechanistic basis is still poorly understood. The objective of this study is
      to explore the regulatory mechanism for starch biosynthesis and degradation in
      plant source organs. Using transmission electron microscopy, we observed that
      during the day after anthesis, starch granules in mesophyll cells of wheat flag
      leaves accumulated in chloroplasts and the number of starch granules gradually
      decreased with wheat leaf growth. During the night, starch granules synthesized
      in chloroplasts during the day were completely or partially degraded. The
      transcript levels of 26 starch synthesis-related genes and 16 starch breakdown
      related genes were further measured using quantitative real-time reverse
      transcription polymerase chain reaction. Expression profile analysis revealed
      that starch metabolism genes were clustered into two groups based on their
      temporal expression patterns. The genes in the first group were highly expressed
      and presumed to play crucial roles in starch metabolism. The genes in the other
      group were not highly expressed in flag leaves and may have minor functions in
      starch metabolism in leaf tissue. The functions of most of these genes in leaves
      were further discussed. The starch metabolism-related genes that are
      predominantly expressed in wheat flag leaves differ from those expressed in wheat
      grain, indicating that two different pathways for starch metabolism operate in
      these tissues. This provides specific information on the molecular mechanisms of
      transitory starch metabolism in higher plants. 

PMID- 24853501
TI  - Coliphage HK022 Nun protein inhibits RNA polymerase translocation.
AB  - The Nun protein of coliphage HK022 arrests RNA polymerase (RNAP) in vivo and in
      vitro at pause sites distal to phage lambda N-Utilization (nut) site RNA
      sequences. We tested the activity of Nun on ternary elongation complexes (TECs)
      assembled with templates lacking the lambda nut sequence. We report that Nun
      stabilizes both translocation states of RNAP by restricting lateral movement of
      TEC along the DNA register. When Nun stabilized TEC in a pretranslocated
      register, immediately after NMP incorporation, it prevented binding of the next
      NTP and stimulated pyrophosphorolysis of the nascent transcript. In contrast,
      stabilization of TEC by Nun in a posttranslocated register allowed NTP binding
      and nucleotidyl transfer but inhibited pyrophosphorolysis and the next round of
      forward translocation. Nun binding to and action on the TEC requires a 9-bp RNA
      DNA hybrid. We observed a Nun-dependent toe print upstream to the TEC. In
      addition, mutations in the RNAP beta' subunit near the upstream end of the
      transcription bubble suppress Nun binding and arrest. These results suggest that
      Nun interacts with RNAP near the 5' edge of the RNA-DNA hybrid. By stabilizing
      translocation states through restriction of TEC lateral mobility, Nun represents
      a novel class of transcription arrest factors. 

PMID- 24853503
TI  - Remnant of stripe order.

PMID- 24853502
TI  - Intestinal cell kinase, a protein associated with endocrine-cerebro
      osteodysplasia syndrome, is a key regulator of cilia length and Hedgehog
      signaling.
AB  - Endocrine-cerebro-osteodysplasia (ECO) syndrome is a recessive genetic disorder
      associated with multiple congenital defects in endocrine, cerebral, and skeletal
      systems that is caused by a missense mutation in the mitogen-activated protein
      kinase-like intestinal cell kinase (ICK) gene. In algae and invertebrates, ICK
      homologs are involved in flagellar formation and ciliogenesis, respectively.
      However, it is not clear whether this role of ICK is conserved in mammals and how
      a lack of functional ICK results in the characteristic phenotypes of human ECO
      syndrome. Here, we generated Ick knockout mice to elucidate the precise role of
      ICK in mammalian development and to examine the pathological mechanisms of ECO
      syndrome. Ick null mouse embryos displayed cleft palate, hydrocephalus,
      polydactyly, and delayed skeletal development, closely resembling ECO syndrome
      phenotypes. In cultured cells, down-regulation of Ick or overexpression of kinase
      dead or ECO syndrome mutant ICK resulted in an elongation of primary cilia and
      abnormal Sonic hedgehog (Shh) signaling. Wild-type ICK proteins were generally
      localized in the proximal region of cilia near the basal bodies, whereas kinase
      dead ICK mutant proteins accumulated in the distal part of bulged ciliary tips.
      Consistent with these observations in cultured cells, Ick knockout mouse embryos
      displayed elongated cilia and reduced Shh signaling during limb digit patterning.
      Taken together, these results indicate that ICK plays a crucial role in
      controlling ciliary length and that ciliary defects caused by a lack of
      functional ICK leads to abnormal Shh signaling, resulting in congenital disorders
      such as ECO syndrome. 

PMID- 24853504
TI  - Clearing tail-anchored proteins from mitochondria.

PMID- 24853505
TI  - Large-scale comparison of science teaching methods sends clear message.

PMID- 24853506
TI  - A "microRNA-like" small RNA expressed by Dengue virus?

PMID- 24853507
TI  - Biotic and abiotic variables affecting internalization and fate of Escherichia
      coli O157:H7 isolates in leafy green roots.
AB  - Preharvest internalization of Escherichia coli O157:H7 into the roots of leafy
      greens is a food safety risk because the pathogen may be systemically transported
      to edible portions of the plant. In this study, both abiotic (degree of soil
      moisture) and biotic (E. coli O157:H7 exposure, presence of Shiga toxin genes,
      and type of leafy green) factors were examined to determine their potential
      effects on pathogen internalization into roots of leafy greens. Using field soil
      that should have an active indigenous microbial community, internalized
      populations in lettuce roots were 0.8 to 1.6 log CFU/g after exposure to soil
      containing E. coli O157:H7 at 5.6 to 6.1 log CFU/g. Internalization of E. coli
      O157:H7 into leafy green plant roots was higher when E. coli O157:H7 populations
      in soil were increased to 7 or 8 log CFU/g or when the soil was saturated with
      water. No differences were noted in the extent to which internalization of E.
      coli O157:H7 occurred in spinach, lettuce, or parsley roots; however, in
      saturated soil, maximum levels in parsley occurred later than did those in
      spinach or lettuce. Translocation of E. coli O157:H7 from roots to leaves was
      rare; therefore, decreases observed in root populations over time were likely the
      result of inactivation within the plant tissue. Shiga toxin-negative
      (nontoxigenic) E. coli O157:H7 isolates were more stable than were virulent
      isolates in soil, but the degree of internalization of E. coli O157:H7 into roots
      did not differ between isolate type. Therefore, these nontoxigenic isolates could
      be used as surrogates for virulent isolates in field trials involving
      internalization.

PMID- 24853508
TI  - Arcobacter: comparison of isolation methods, diversity, and potential pathogenic
      factors in commercially retailed chicken breast meat from Costa Rica.
AB  - Arcobacter species have been recognized as potential food- and waterborne
      pathogens. The lack of standardized isolation methods and the relatively scarce
      knowledge about their prevalence and distribution as emerging pathogens are due
      to the limitations in their detection and identification. This study aimed to
      determine the presence and the identification of Arcobacter in chicken breast
      samples commercially retailed in San Jose, Costa Rica, as well as to describe the
      adherence and invasive potential of the strains to human cells (HEp-2). Fifty
      chicken breast samples were collected from retail markets in the metropolitan
      area of the country. Six different isolation methodologies were applied for the
      isolation of Arcobacter. Isolation strategies consisted of combinations of
      enrichments in de Boer or Houf selective broths and subsequent isolation in blood
      agar (directly or with a previous passive membrane filtration step) or Arcobacter
      selective agar. Suspicious colonies were identified with a genus-specific PCR,
      whereas species-level identification was achieved with a multiplex PCR. The
      overall isolation frequency of Arcobacter was 56%. From the isolation strategies,
      the combination of enrichment in Houf selective broth followed by filtration on
      blood agar showed the best performance, with a sensitivity of 89% and a
      specificity of 84%. A total of 46 isolates were confirmed as Arcobacter with the
      genus-specific PCR, from which 27 (59%) corresponded to Arcobacter butzleri, 9
      (19%) to Arcobacter cryaerophilus, and 10 (22%) were not identified with this
      multiplex PCR. Regarding the potential pathogenicity, 75% of the isolates
      presented adherence to HEp-2 cells, while only 22% were invasive to that cell
      line. All invasive strains were A. butzleri or nonidentified strains. The results
      show the presence of potentially pathogenic Arcobacter in poultry and recognize
      the importance it should receive as a potential foodborne pathogen from public
      health authorities.

PMID- 24853509
TI  - Prevalence, concentrations, and antibiotic sensitivities of Salmonella serovars
      in poultry from retail establishments in Seattle, Washington.
AB  - Poultry have been identified as one of the major sources of salmonellosis, with
      estimates ranging from 10 to 22% of total cases. Despite several advances in the
      industry and new performance standards, the incidence of salmonellosis in the
      population has not declined over the last 15 years. Salmonella is pervasive in a
      wide variety of foods, and thus, estimating its burden resulting from specific
      food categories has been challenging and plagued with uncertainty due to critical
      data gaps. The objective of this study was to conduct a year-long market survey
      (1,322 samples) to help bridge the data gaps on the contamination rates and
      levels of Salmonella on raw poultry by product type (i.e., breast, thighs, drums,
      wings, and split breast) and production method (conventional versus organic). The
      isolates recovered were serotyped and tested for antibiotic sensitivities. A PCR
      method was utilized for initial screening of samples after an overnight
      enrichment in tryptic soy broth. Three-tube most-probable-number (MPN) assays and
      anti-Salmonella immunomagnetic separation methods were utilized to determine the
      levels of Salmonella and aid with the recovery of Salmonella species,
      respectively. Eleven percent of the samples were positive for Salmonella.
      Significant differences in percent positive rates by product type included up to
      a 4-fold difference in percent positive rates between establishments, ranging
      from 7 to 31%. Of the samples positive for Salmonella species, 94% had <30
      MPN/100 g. Production methods identified as organic or as not using antibiotics
      had significantly higher rates of recovery of Salmonella. On the other hand, all
      of the Salmonella isolates that were resistant to two or more antibiotics
      originated from conventional processing establishments where antibiotics were
      utilized. In addition, a significant proportion of isolates from conventionally
      processed products were serotypes clinically relevant to humans.

PMID- 24853510
TI  - Counts, serotypes, and antimicrobial resistance of Salmonella isolates on retail
      raw poultry in the People's Republic of China.
AB  - The objective of this study was to determine Salmonella counts, serotypes, and
      antimicrobial resistance profiles in retail raw chicken meat in the People's
      Republic of China. Salmonella counts were determined according to the most
      probable-number (MPN) method for 300 whole chicken carcasses. These samples were
      collected from large, small, and wet (open) markets in Guangdong, Shaanxi, and
      Sichuan provinces. Salmonella isolates were serotyped and tested for
      antimicrobial susceptibility. Of the 300 chicken carcasses, 43.3% were positive
      for Salmonella, with an overall mean of 1.7 log MPN per carcass (95% confidence
      interval, 1.6 to 1.8 log MPN per carcass). No significant differences (P > 0.05)
      were detected for storage temperature (i.e., chilled, frozen, or ambient), market
      type (large, small, or wet), province, or location (capital or noncapital city).
      Seventy-eight serotypes were identified among the 1,094 Salmonella isolates. The
      top five most common Salmonella serotypes on raw chicken carcasses were
      Enteritidis (19.2%), Indiana (15.2%), Typhimurium (14.6%), Agona (7.1%), and
      Thompson (6.6%). Salmonella isolates (n = 779) were most frequently resistant to
      sulfisoxazole (74.1%) and tetracycline (71.1%) and least resistant to ceftriaxone
      (22.5%) and cefoxitin (19%). Only 4% of the isolates were susceptible to all 15
      antimicrobial agents, 45% were resistant to 1 to 5 agents, 29% were resistant to
      6 to 10 agents, and 22% were resistant to 11 to 15 agents. Our findings revealed
      that Salmonella contamination was common in retail raw poultry in China, and the
      counts on contaminated carcasses were mostly low. Salmonella isolates were
      diverse in their serotype distribution and antimicrobial susceptibility profiles,
      with more than half of the isolates resistant to more than five antimicrobial
      agents. These data may be used in risk assessment models to reduce the
      transmission of Salmonella via chicken meat to humans in China.

PMID- 24853511
TI  - Comparing the behavior of multidrug-resistant and pansusceptible Salmonella
      during the production and aging of a Gouda cheese manufactured from raw milk.
AB  - Outbreaks of salmonellosis have been linked to the consumption of cheese, and
      emerging multidrug-resistant (MDR) strains of Salmonella may be more virulent and
      more tolerant than less resistant strains to stresses encountered in food
      production, which may enhance the survival of these resistant strains in cheese.
      This study was conducted to compare the behavior of MDR and pansusceptible
      Salmonella strains during the manufacture and aging of Gouda cheese and compare
      pathogen recovery via several rapid and traditional methods. Cheeses were
      manufactured from raw milk inoculated with a six-strain cocktail of either MDR or
      susceptible Salmonella Newport and Salmonella Typhimurium at initial levels of
      <20 CFU/ml. Samples of milk, whey, curd, and finished cheese were analyzed using
      eight enrichment and detection protocols. Overall, changes in pathogen levels
      observed throughout manufacture and aging did not differ significantly between
      MDR and susceptible Salmonella strains. Salmonella counts increased significantly
      during manufacture to a mean of 734 CFU/g on day 1 followed by a significant
      decrease over 60 days of aging to <1 CFU/g. Although levels fell and stayed below
      the direct plating detection limit of $ 5 CFU/g after 54 days on average, viable
      cells remained detectable after enrichment for an average of 210 +/- 40 days. The
      International Organization for Standardization methods with and without PCR
      detection provided the most accurate results, and the remaining methods, notably
      those with selective primary incubation, produced results that disagreed
      significantly with the true result. Overall, our findings suggest that MDR
      Salmonella strains may not pose a greater threat to cheese safety than do non-MDR
      Salmonella strains.

PMID- 24853512
TI  - Changes in thermal resistance of three Salmonella serovars in response to osmotic
      shock and adaptation at water activities reduced by different humectants.
AB  - The purpose of this study was to investigate the effect of osmotic shock and
      adaptation at low water activity (aw) and the type of humectant used to lower the
      aw, on heat resistance of three Salmonella enterica serovars (Saintpaul 02-109,
      Tennessee 2053H, and Elmsbuettel 1236H). The serovars were grown (adapted) or
      transferred (osmotic shocked) in low-aw broths and subjected to heat treatment at
      55 degrees C for up to 45 min; samples were removed at 5-min intervals and
      immediately placed in an ice-water bath until plating. The aw of tryptic soy
      broth (TSB) was lowered by the addition of 20% (wt/wt) glycerol (aw 0.94), 4%
      (wt/wt) sodium chloride (NaCl; aw 0.97), or 35% sucrose (wt/wt) (aw 0.95). The
      type of humectant and cell adaptation significantly affected the D55 degrees C
      value. Cells merely suspended in 20% glycerol broth (i.e., nonadapted) prior to
      heat treatment showed a larger D55 degrees C-value (3.0 to 3.9 min), when
      compared with that of cells adapted in the same medium (D55 degrees C-values of
      0.86 to 0.98 min). Interestingly, cells adapted to TSB plus glycerol were not
      more resistant to heat than were the controls. NaCl and sucrose showed a net
      protective effect for all serovars under both the adapted and nonadapted
      conditions, with sucrose providing the most protection. Highest D55 degrees C
      values were obtained for cultures adapted to TSB plus sucrose. Based on these
      results, the effect of reduced aw on thermal resistance of Salmonella serovars
      varies greatly, depending on medium constituents and adaptation of the pathogen
      in these media.

PMID- 24853513
TI  - Effects of selected cooking procedures on the survival of Escherichia coli
      O157:H7 in inoculated steaks cooked on a hot plate or gas barbecue grill.
AB  - Beef steaks (2 cm thick) were each inoculated at three sites in the central plane
      with Escherichia coli O157:H7 at 5.9 +/- 0.3 log CFU per site. Temperatures at
      steak centers were monitored during cooking on a hot plate or the grill of a gas
      barbeque. Steaks were cooked in groups of five using the same procedures and
      cooking each steak to the same temperature, and surviving E. coli O157:H7 at each
      site was enumerated. When steaks cooked on the hot plate were turned over every 2
      or 4 min during cooking to between 56 and 62 degrees C, no E. coli O157:H7 was
      recovered from steaks cooked to >=58 or 62 degrees C, respectively. When steaks
      were cooked to <=71 degrees C and turned over once during cooking, E. coli
      O157:H7 was recovered from steaks in groups turned over after <=8 min but not
      from steaks turned over after 10 or 12 min. E. coli O157:H7 was recovered in
      similar numbers from steaks that were not held or were held for 3 min after
      cooking when steaks were turned over once after 4 or 6 min during cooking. When
      steaks were cooked on the grill with the barbeque lid open and turned over every
      2 or 4 min during cooking to 63 or 56 degrees C, E. coli O157:H7 was recovered
      from only those steaks turned over at 4-min intervals and cooked to 56 degrees C.
      E. coli O157:H7 was recovered from some steaks turned over once during cooking on
      the grill and held or not held after cooking to 63 degrees C. E. coli O157:H7 was
      not recovered from steaks turned over after 4 min during cooking to 60 degrees C
      on the grill with the barbeque lid closed or when the lid was closed after 6 min.
      Apparently, the microbiological safety of mechanically tenderized steaks can be
      assured by turning steaks over at intervals of about 2 min during cooking to >=60
      degrees C in an open skillet or on a barbecue grill. When steaks are turned over
      only once during cooking to >=60 degrees C, microbiological safety may be assured
      by covering the skillet or grill with a lid during at least the final minutes of
      cooking.

PMID- 24853514
TI  - inhibitory effects of citral, cinnamaldehyde, and tea polyphenols on mixed
      biofilm formation by foodborne Staphylococcus aureus and Salmonella enteritidis.
AB  - Biofilms are significant hazards in the food industry. In this study, we
      investigated the effects of food additive such as citral, cinnamaldehyde, and tea
      polyphenols on mixed biofilm formation by foodborne Staphylococcus aureus and
      Salmonella serotype Enteritidis. The adhesion rates of mixed strains in sub-MIC
      of additives were determined by a microtiter plate assay and bacterial
      communication signal autoinducer 2 (AI-2) production via a bioluminescence
      reporter Vibrio harveyi BB170. The structure of mixed biofilm was analyzed using
      scanning electron microscopy. The effect of the disinfectants hydrogen peroxide,
      sodium hypochlorite, and peracetic acid was tested on the mixed biofilm. Our
      results demonstrated that citral, cinnamaldehyde, and tea polyphenols were able
      to significantly inhibit mixed biofilm formation, while citral could reduce the
      synthesis of AI-2. Conversely, we observed a significant increase in AI-2
      mediated by cinnamaldehyde. Tea polyphenols at lower concentrations induced AI-2
      synthesis; however, AI-2 synthesis was significantly inhibited at higher
      concentrations (300 m g/ml). Food additives inhibited the adhesion of mixed
      bacteria on stainless steel chips and increased the sensitivity of the mixed
      biofilm to disinfectants. In conclusion, citral, cinnamaldehyde, and tea
      polyphenols had strong inhibitory effects on mixed biofilm formation and also
      enhanced the effect of disinfectant on mixed biofilm formation. This study
      provides a scientific basis for the application of natural food additives to
      control biofilm formation of foodborne bacteria.

PMID- 24853515
TI  - Temperature effects on the antimicrobial efficacy of condensed smoke and lauric
      arginate against Listeria and Salmonella.
AB  - Condensed smoke or liquid smoke (LS) and lauric arginate (LAE) are antimicrobials
      used in food preservation. They have demonstrated abilities to reduce or inhibit
      pathogenic and spoilage organisms. Few studies, however, have reported on the
      effectiveness of LS or LAE over the range of temperatures typically encountered
      in food marketing channels. Therefore, the effects of temperature on the
      antimicrobial properties of two commercial LS fractions, an LS derived from pecan
      shells, and LAE against two common foodborne pathogens, Listeria and Salmonella,
      were investigated. The MICs of the three LS samples and LAE were measured at 4,
      10, and 37 degrees C for Listeria monocytogenes strains 2045 (Scott A, serotype
      4b) and 10403S (serotype 1/2a) and two strains of Listeria innocua, a well
      established surrogate, and at 10, 25, and 37 degrees C for Salmonella enterica
      serovar Typhimurium and Salmonella enterica serovar Heidelberg. The MICs for LS
      against Listeria ranged from 3 to 48% (vol/vol), with higher MICs seen with lower
      temperatures. The MICs for LS on Salmonella ranged from 3 to 24%. Values for LAE
      ranged between 0.004 and 0.07% for both pathogens, and like LS, higher MICs were
      always associated with lower incubation temperatures. Understanding how storage
      temperature affects the efficacy of antimicrobials is an important factor that
      can contribute to lowering the hurdles of use levels and costs of antimicrobials
      and ultimately improve food safety for the consumer.

PMID- 24853516
TI  - Rapid detection of bacteria in green tea using a novel pretreatment method in a
      bioluminescence assay.
AB  - Tea is one of the most popular beverages consumed in the world, and green tea has
      become a popular beverage in Western as well as Asian countries. A novel
      pretreatment method for a commercial bioluminescence assay to detect bacteria in
      green tea was developed and evaluated in this study. Pretreatment buffers with pH
      levels ranging from 6.0 to 9.0 were selected from MES (morpholineethanesulfonic
      acid), HEPES (N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid), or Tricine
      buffers. To evaluate the effect of pretreatment and the performance of the assay,
      serially diluted cultures of Enterobacter cloacae, Escherichia coli, Bacillus
      subtilis, and Staphylococcus aureus were tested. The improved methods, which
      consisted of a pretreatment of the sample in alkaline buffer, significantly
      decreased the background bioluminescence intensity of green tea samples when
      compared with the conventional method. Pretreatment with alkaline buffers with pH
      levels ranging from 8.0 to 9.0 increased the bioluminescence intensities of
      cultures of E. cloacae and S. aureus. Strong log-linear relationships between the
      bioluminescence intensities and plate counts emerged for the tested strains.
      Furthermore, the microbial detection limit was 15 CFU in 500 ml of bottled green
      tea after an 8-h incubation at 35 degrees C and an assay time of 1 h. The results
      showed that contaminated samples could be detected within 1 h of operation using
      our improved bioluminescence assay. This method could be used to test for
      contamination during the manufacturing process as well as for statistical
      sampling for quality control.

PMID- 24853517
TI  - Screening foods for processing-resistant bacterial spores and characterization of
      a pressure- and heat-resistant Bacillus licheniformis isolate.
AB  - This study was carried out to isolate pressure- and heat-resistant indicator
      spores from selected food matrices (black pepper, red pepper, garlic, and potato
      peel). Food samples were processed under various thermal (90 to 105 degrees C)
      and pressure (700 MPa) combination conditions, and surviving microorganisms were
      isolated. An isolate from red pepper powder, Bacillus licheniformis, was highly
      resistant to pressure-thermal treatments. Spores of the isolate in deionized
      water were subjected to the combination treatments of pressure (0.1 to 700 MPa)
      and heat (90 to 121 degrees C). Compared with the thermal treatment, the combined
      pressure-thermal treatments considerably reduced the numbers of B. licheniformis
      spores to less than 1.0 log CFU/g at 700 MPa plus 105 degrees C and at 300 to 700
      MPa plus 121 degrees C. The inactivation kinetic parameters of the isolated B.
      licheniformis spores were estimated using linear and nonlinear models. Within the
      range of the experimental conditions tested, the pressure sensitivity (zP) of the
      spores decreased with increasing temperature (up to 121 degrees C), and the
      temperature sensitivity (zT) was maximum at atmospheric pressure (0.1 MPa). These
      results will be useful for developing a combined pressure-thermal inactivation
      kinetics database for various bacterial spores.

PMID- 24853518
TI  - Ovotransferrin plays a major role in the strong bactericidal effect of egg white
      against the Bacillus cereus group.
AB  - Bacillus cereus group bacteria are opportunistically pathogenic spore-forming
      microorganisms well known in the sector of pasteurized food products because of
      their involvement in spoilage events. In the sector of egg product processing,
      these bacteria may lead to important economic losses. It seemed then relevant to
      study their behavior in egg white, a widely used egg product usually recognized
      as developing different levels of antimicrobial activities depending on the
      environmental conditions. A strong bactericidal effect (decrease in the bacterial
      population of 6.1 +/- 0.2 log CFU/ml) was observed for 68 B. cereus group
      isolates, independently incubated at 30 degrees C in egg white at pH 9.3 (natural
      egg white pH). To determine which components could explain such a strong
      bactericidal effect, an experimental strategy was carried out, based on egg white
      fractionation by ultrafiltration and by anion-exchange liquid chromatography. The
      role of the protein fraction was thus demonstrated, and subsequent nano-liquid
      chromatography-tandem mass spectrometry analyses allowed identification of
      ovotransferrin as a major protein involved. The strong bactericidal effect was
      confirmed in the presence of commercial ovotransferrin. Such a bactericidal
      effect (i.e., a decrease in the bacterial population through cell death) had
      never been described because ovotransferrin is known for its bacteriostatic
      effect (i.e., inhibition of growth) due to its ability to chelate iron.
      Surprisingly, the addition of iron did not reverse the bactericidal effect of
      ovotransferrin under alkaline conditions (pH 9.3), whereas it completely reversed
      this effect at pH 7.3. Ovotransferrin was shown to provoke a perturbation of the
      electrochemical potential of the cytoplasmic membrane. A membrane disturbance
      mechanism could, hence, be involved, leading to the lysis of B. cereus group
      bacteria incubated in egg white.

PMID- 24853519
TI  - Reduction of patulin in apple juice products by UV light of different wavelengths
      in the UVC range.
AB  - This study evaluated three UVC wavelengths (222, 254, and 282 nm) to degrade
      patulin introduced into apple juice or apple cider. The average UV fluences of
      19.6, 84.3, 55.0, and 36.6 mJ.cm(-2) achieved through exposure to UV lamps at 222
      , 254-, and 282-nm wavelengths and the combination of these wavelengths,
      respectively, resulted in 90% reduction of patulin in apple juice. Therefore, the
      order of efficiency of the three wavelength lamps was as follows: far UVC (222
      nm) > far UVC plus (282 nm) > UVC (254 nm). In terms of color, treatment of apple
      juice with 222 nm resulted in an increase in the L* (lightness) value but
      decreases in a* (redness) and b* (yellowness) values, although the changes were
      insignificantly different from the values for nontreated controls based on a
      sensory evaluation. The ascorbic acid loss in juice treated at 222 nm to support
      90% reduction of patulin was 36.5%, compared with ascorbic acid losses of 45.3
      and 36.1% in samples treated at 254 and 282 nm, respectively. The current work
      demonstrated that the 222-nm wavelength possesses the highest efficiency for
      patulin reduction in apple juice when compared with the reductions by 254 and 282
      nm, with no benefit gained from using a combination of wavelengths.

PMID- 24853520
TI  - Relative sensitivity of Escherichia coli O157 detection from bovine feces and
      rectoanal mucosal swabs.
AB  - The need to quantify the potential human health risk posed by the bovine
      reservoir of Escherichia coli O157 has led to a wealth of prevalence studies and
      improvements in detection methods over the last two decades. Rectoanal mucosal
      swabs have been used for the detection of E. coli O157 fecal shedding, colonized
      animals, and those predisposed to super shedding. We conducted a longitudinal
      study to compare the detection of E. coli O157 from feces and rectoanal mucosal
      swabs (RAMS) from a cohort of dairy heifers. We collected 820 samples that were
      tested by immunomagnetic separation of both feces and RAMS. Of these, 132 were
      detected as positive for E. coli O157 from both samples, 66 were detected as
      positive from RAMS only, and 117 were detected as positive from feces only. The
      difference in results between the two sample types was statistically significant
      (P < 0.001). The relative sensitivities of detection by immunomagnetic separation
      were 53% (confidence interval, 46.6 to 59.3) from RAMS and 67% (confidence
      interval, 59.6 to 73.1) from fecal samples. No association between long-term
      shedding (P = 0.685) or super shedding (P = 0.526) and detection by RAMS only was
      observed.

PMID- 24853521
TI  - Infrared sensor-based aerosol sanitization system for controlling Escherichia
      coli O157:H7, Salmonella Typhimurium, and Listeria monocytogenes on fresh
      produce.
AB  - An economical aerosol sanitization system was developed based on sensor
      technology for minimizing sanitizer usage, while maintaining bactericidal
      efficacy. Aerosol intensity in a system chamber was controlled by a position
      sensitive device and its infrared value range. The effectiveness of the infrared
      sensor-based aerosolization (ISA) system to inactivate Escherichia coli O157:H7,
      Salmonella Typhimurium, and Listeria monocytogenes on spinach leaf surfaces was
      compared with conventional aerosolization (full-time aerosol treated), and the
      amount of sanitizer consumed was determined after operation. Three pathogens
      artificially inoculated onto spinach leaf surfaces were treated with aerosolized
      peracetic acid (400 ppm) for 15, 30, 45, and 60 min at room temperature (22 +/- 2
      degrees C). Using the ISA system, inactivation levels of the three pathogens were
      equal or better than treatment with conventional full-time aerosolization.
      However, the amount of sanitizer consumed was reduced by ca. 40% using the ISA
      system. The results of this study suggest that an aerosol sanitization system
      combined with infrared sensor technology could be used for transportation and
      storage of fresh produce efficiently and economically as a practical commercial
      intervention.

PMID- 24853522
TI  - Effects of Ocimum basilicum Linn essential oil and sodium hexametaphosphate on
      the shelf life of fresh chicken sausage.
AB  - Although consumers and the food industry have an interest in reducing the use of
      synthetic additives, the consumption of processed meat in Brazil has been
      increasing because of the easy preparation and low cost. Owing to the
      antimicrobial and antioxidative properties of Ocimum basilicum essential oil
      (EO), it has potential applications in food products. Polyphosphates are already
      used in meat processing with the goal of improving the quality of the products.
      The aim of this work was to assess the effects of sodium hexametaphosphate (SHMP)
      and O. basilicum EO, when added separately or together, on physical, chemical,
      and microbiological parameters during the shelf life of chicken sausage. We also
      performed sensory analysis of the product prepared in this manner. Six different
      treatments were produced in which the substances were tested together or
      separately, and the content of EO was 0.3 or 0.03%. The samples were analyzed
      after 1, 7, and 15 days of storage at 4 degrees C. An increase in pH on days 7
      and 15 in samples that contained SHMP was observed. In the samples that contained
      either 0.3 or 0.03% EO, coliforms were inhibited throughout the study period (P <
      0.05), which was not observed in samples with EO plus SHMP, thus demonstrating
      that the stabilizer blocked the antibacterial action of EO. There was a reduction
      in the cook loss and increased compressive force in the samples with 0.5% SHMP,
      contributing to greater juiciness of the product. The EO had substantial impact
      on acceptability of samples, but it did not influence the activities already
      described of polyphosphate.

PMID- 24853523
TI  - Viability of Listeria monocytogenes on uncured turkey breast commercially
      prepared with and without buffered vinegar during extended storage at 4 and 10
      degrees C.
AB  - We determined the viability of Listeria monocytogenes on uncured turkey breast
      containing buffered vinegar (BV) and surface treated with a stabilized solution
      of sodium chlorite in vinegar (VSC). Commercially produced, uncured, deli-style
      turkey breast was formulated with BV (0.0, 2.0, 2.5, or 3.0%), sliced (ca. 100 g
      and ca. 1.25 cm thick), and subsequently surface inoculated (ca. 4.3 log CFU per
      slice) in each of two trials with a five-strain cocktail of L. monocytogenes.
      Next, 1 ml per side of a 2 or 10% solution of VSC was added to each package
      before vacuum sealing and storing at 4 or 10 degrees C. Without antimicrobials,
      L. monocytogenes numbers increased by ca. 6.2 log CFU per slice after 90 and 48
      days of storage at 4 or 10 degrees C, respectively. At 4 degrees C, L.
      monocytogenes numbers increased by ca. 0.4 to 1.9 log CFU per slice on turkey
      breast formulated with 2.0 or 2.5% BV and treated or not with 2% VSC, whereas
      when treated with 10% VSC, L. monocytogenes levels remained relatively unchanged
      over 90 days. However, when turkey breast was formulated with 3.0% BV and treated
      or not with VSC, pathogen numbers decreased by ca. 0.7 to 1.3 log CFU per slice.
      At 10 degrees C, L. monocytogenes numbers increased by ca. 1.5 to 5.6 log CFU per
      slice after 48 days when formulated with 2.0 to 3.0% BV and treated or not with
      2% VSC. When formulated with 2.0% BV and treated with 10% VSC, L. monocytogenes
      numbers increased by ca. 3.3 log CFU per slice, whereas when formulated with 2.5
      or 3.0% BV and treated with 10% VSC, L. monocytogenes decreased by ca. 0.3 log
      CFU per slice. Inclusion of BV as an ingredient in uncured turkey breast, alone
      or in combination with VSC added to the package, appreciably suppressed outgrowth
      of L. monocytogenes during an extended refrigerated shelf life.

PMID- 24853524
TI  - Retail ready-to-eat food as a potential vehicle for Staphylococcus spp. harboring
      antibiotic resistance genes.
AB  - Ready-to-eat (RTE) food, which does not need thermal processing before
      consumption, could be a vehicle for the spread of antibiotic-resistant
      microorganisms. As part of general microbiological safety checks, staphylococci
      are routinely enumerated in these kinds of foods. However, the presence of
      antibiotic-resistant staphylococci in RTE food is not routinely investigated, and
      data are only available from a small number of studies. The present study
      evaluated the pheno- and genotypical antimicrobial resistance profile of
      Staphylococcus spp. isolated from 858 RTE foods (cheeses, cured meats, sausages,
      smoked fishes, salads). Of 113 strains isolated, S. aureus was the most prevalent
      species, followed by S. xylosus, S. saprophyticus, and S. epidermidis. More than
      half (54.9%) of the isolates were resistant to at least one class of tested
      antibiotic; of these, 35.4% of the strains were classified as multidrug
      resistant. Most of the isolates were resistant to cefoxitin (49.6%), followed by
      clindamycin (39.3%), tigecycline (27.4%), quinupristin-dalfopristin (22.2%),
      rifampin (20.5%), tetracycline (17.9%), and erythromycin (8.5%). All methicillin
      resistant staphylococci harbored the mecA gene. Among the isolates resistant to
      at least one antibiotic, 38 harbored tetracycline resistance determinant tet (M),
      24 harbored tet (L), and 9 harbored tet (K). Of the isolates positive for tet (M)
      genes, 34.2% were positive for the Tn916-Tn1545-like integrase family gene. Our
      results indicated that retail RTE food could be considered an important route for
      the transmission of antibiotic-resistant bacteria harboring multiple antibiotic
      resistance genes.

PMID- 24853525
TI  - Reproducibility study for the detection of Staphylococcal enterotoxins in dairy
      products between official Italian national laboratories.
AB  - Staphylococcal food poisoning is a common foodborne disease caused by the
      ingestion of staphylococcal enterotoxins (SEs) produced mainly by enterotoxigenic
      strains of Staphylococcus aureus. To date, 21 SEs and/or enterotoxin-like types
      have been identified, several of which represent a potential hazard for
      consumers. To protect consumer health and to reduce the amount of SE-contaminated
      food entering the market, European Union legislation regulating food safety
      requires testing for SEs. The Italian National Reference Laboratory organized a
      ring trial to test technical and analytical proficiency in the national network
      of official food laboratories. Twenty-four laboratories took part, and each
      received and analyzed 24 blind dairy samples. Reproducibility of the results from
      the laboratories was assessed by the Cohen k index, and accuracy (sensitivity and
      specificity) was evaluated according to the International Organization for
      Standardization definition (ISO 16140:2003). Trial results revealed partially
      satisfactory agreement: 254 of 276 possible paired participants (92%) reached a k
      value >0.60, which is conventionally recognized as satisfactory. Accuracy was
      deemed satisfactory; 100% sensitivity and 100% specificity were achieved by 22
      and 18 of the 24 laboratories, respectively.

PMID- 24853526
TI  - Survey of ochratoxin A in freshly harvested durum and hard red spring wheat in
      the United States, 2011 and 2012.
AB  - Ochratoxin A (OTA) is a toxin produced by some Penicillium and Aspergillus
      species around the world in a variety of food and feed, especially cereal grains,
      before harvest but primarily during storage. Durum and hard red spring (HRS)
      wheat samples were collected right after harvest as part of the U. S. regional
      crop quality survey in both 2011 (n = 560) and 2012 (n = 654) from the upper
      Great Plains. All samples were analyzed for OTA contamination using high
      performance liquid chromatography with fluorescence detection. Overall, 2.1% of
      the samples were positive for OTA. In 2011, OTA was detected in 1.0% of the durum
      wheat samples but was not found in HRS wheat. In 2012, 8.3 and 1.4% of the durum
      and HRS wheat samples, respectively, were positive for OTA. Of the 25 samples
      that had detectable OTA, 3 samples (12%), all of which were durum wheat, had OTA
      that exceeded 5 ng/g.

PMID- 24853527
TI  - An evaluation of aflatoxin and cyclopiazonic acid production in Aspergillus
      oryzae.
AB  - To date, edible fungi such as Aspergillus flavus var. oryzae (A. oryzae) has been
      considered as safe. However, some strains can produce mycotoxins. Thus, the
      biosynthetic ability to produce mycotoxins should be reevaluated to determine the
      safety of edible fungi. We analyzed the production of aflatoxins and
      cyclopiazonic acid (CPA) from edible fungi such as A. oryzae isolated from
      various Korean foods using multiplex PCR, enzyme-linked immunosorbent assay, and
      high-performance liquid chromatography (HPLC). In the multiplex PCR analysis of
      aflatoxin biosynthetic genes omtB, aflR, ver-1, and omtA, 5 of 19 Aspergillus
      strains produced all PCR products. Among them, aflatoxin B1 and aflatoxin B2 were
      detected from only A. flavus KACC 41403 by HPLC. Aflatoxins were not detected
      from the other four strains that produced all positive PCR bands. Aflatoxin also
      was not detected from 12 strains that had PCR patterns without aflR or ver-1 and
      from 2 strains that did not produce any of the expected PCR products. Only the
      seven A. oryzae strains that produced all of the positive PCR bands including the
      CPA biosynthetic genes maoA, dmaT, and pks-nrps produced CPA. CPA and aflatoxin
      production must be evaluated before A. oryzae strains are used for the
      development of fermented foods.

PMID- 24853528
TI  - Withdrawal times of oxytetracycline and tylosin in eggs of laying hens after oral
      administration.
AB  - Antimicrobials administered to laying hens may be distributed into egg white or
      yolk, indicating the importance of evaluating withdrawal times (WDTs) of the
      pharmaceutical formulations. In the present study, oxytetracycline and tylosin's
      WDTs were estimated. The concentration and depletion of these molecules in eggs
      were linked to their pharmacokinetic and physicochemical properties. Twenty-seven
      Leghorn hens were used: 12 treated with oxytetracycline, 12 treated with tylosin,
      and 3 remained as an untreated control group. After completion of therapies, eggs
      were collected daily and drug concentrations in egg white and yolk were assessed.
      The yolk was used as the target tissue to evaluate the WDT; the results were 9
      and 3 days for oxytetracycline and tylosin, respectively. In particular,
      oxytetracycline has a good oral bioavailability, a moderate apparent volume of
      distribution, a molecular weight of 460 g/mol, and is lightly liposoluble.
      Tylosin, a hydrosoluble compound, with a molecular weight of 916 g/mol, has a low
      oral bioavailability and a low apparent volume of distribution, too. Present
      results suggest that the WDTs of the studied antimicrobials are strongly
      influenced by their oral bioavailability, the distribution, and the molecular
      weight and solubility, and that these properties also influence the distribution
      between the egg yolk and white.

PMID- 24853529
TI  - Contents and risk assessment of heavy metals in marine invertebrates from Korean
      coastal fish markets.
AB  - The concentrations of the heavy metals cadmium (Cd), mercury (Hg), lead (Pb),
      chromium, silver, nickel, copper, and zinc in the edible portions of 105 marine
      invertebrates representing 16 mollusk and crustacean species were accurately
      determined to evaluate their hazard for human consumption. The samples were
      collected in 2011 from major fish markets on the coast of Korea and analyzed for
      Hg using a direct Hg analyzer and for other metals using inductively coupled
      plasma mass spectrometry. Estimated dietary exposure (EDE) was determined, and a
      risk assessment was made of the heavy metals to provide information concerning
      consumer safety. The Cd concentrations, which were the highest for the three
      hazardous metals (Cd, Hg, and Pb), were significantly higher (P < 0.05) in the
      bivalves and crabs than in the gastropods and cephalopods. However, the
      concentrations of these metals in all samples were within the regulatory limits
      set by Korea and other countries. The EDE was compared with the provisional
      tolerable daily intake (PTDI) adopted by the Joint FAO/WHO Expert Committee on
      Food Additives or the U.S. Environmental Protection Agency. The EDE of Cd, Hg,
      and Pb for each class of marine invertebrate were 0.07 to 2.64, 0.01 to 0.43, and
      0.001 to 0.16% of the PTDI, respectively. The total EDE of Cd, Hg, and Pb for
      marine invertebrates accounted for 4.03, 0.96, and 0.21%, respectively, of the
      PTDI. The EDE of other metals in each class of marine invertebrate was less than
      2% of the PTDI. The hazard index is a reasonable parameter for assessing the risk
      of heavy metal consumption associated with contaminated food. In the present
      study, the hazard index for all of the species was less than 1.0, which indicates
      that the intake of heavy metals from consumption of these marine invertebrates
      does not represent an appreciable hazard to humans.

PMID- 24853530
TI  - Assessment of food safety risks associated with preslaughter activities during
      the traditional slaughter of goats in Gauteng, South Africa.
AB  - The South African Department of Agriculture, Forestry and Fisheries estimated in
      2012 that there were 2.033 million goats in the country. Of these animals, less
      than 0.5% are slaughtered at registered abattoirs. Although informal and
      traditional slaughter of goats for home consumption is permitted under the South
      African Meat Safety Act 40 of 2000, the responsibility for ensuring that products
      are safe is left to the traditional or ritual slaughter practitioners. The
      objective of the present study was to assess whether preslaughter activities
      associated with traditional or ritual slaughter promote or reduce food-associated
      risks and to recommend mitigation strategies for potential food safety hazards.
      Structured interviews were conducted with 105 selected respondents (in and around
      Tshwane, South Africa) who had been involved in traditional goat slaughter.
      Approximately 70% of goats slaughtered were obtained from sources that could be
      traced to ascertain the origin of the goats. None of the respondents were aware
      of the need for a health declaration for slaughter stock. Some slaughter
      practitioners (21%) perform prepurchase inspection of stock to ascertain their
      health status. However, this percentage is very small, and the approach is based
      on indigenous knowledge systems. The majority of respondents (67.6%) travelled 1
      to 11 km to obtain a goat for traditional slaughter. Although approximately 70%
      of slaughter goats were transported by vehicles, the vehicles used did not meet
      the legal standard. More than two-thirds of goats were tied to a tree while
      waiting to be slaughtered, and the rest were held in a kraal. The holding period
      ranged from 1 to 72 h, but more than 70% of the animals were slaughtered within
      36 h. This study revealed that traditional and ritual slaughter involves some
      preslaughter activities with potential to mitigate the risk of slaughtering
      animals that are not fit for human consumption. Such activities include
      prepurchase inspection, obtaining goats from known and traceable sources, and
      ensuring that animals have sufficient rest before slaughter. However, given the
      rudimentary nature of these activities, they may not offer adequate protection to
      consumers of such meat. The lack of understanding of the importance of a
      obtaining a health declaration certificate and minimizing stress in animals
      waiting to be slaughtered should be addressed to minimize the potential for
      propagation of foodborne diseases. The Meat Safety Act 40 of 2000 should be
      enforced where it applies and should be reviewed to provide guidelines that would
      help mitigate human health risks associated with traditional slaughter of goats.

PMID- 24853531
TI  - Development of a cost-effectiveness analysis of leafy green marketing agreement
      irrigation water provisions.
AB  - An analysis of the effectiveness of meeting the irrigation water provisions of
      the Leafy Green Marketing Agreement (LGMA) relative to its costs provides an
      approach to evaluating the cost-effectiveness of good agricultural practices that
      uses available data. A case example for lettuce is used to evaluate data
      requirements and provide a methodological example to determine the cost
      effectiveness of the LGMA water quality provision. Both cost and field data on
      pathogen or indicator bacterial levels are difficult and expensive to obtain
      prospectively. Therefore, methods to use existing field and experimental data are
      required. Based on data from current literature and experimental studies, we
      calculate a cost-efficiency ratio that expresses the reduction in E. coli
      concentration per dollar expenditure on testing of irrigation water. With
      appropriate data, the same type of analysis can be extended to soil amendments
      and other practices and to evaluation of public benefits of practices used in
      production. Careful use of existing and experimental data can lead to evaluation
      of an expanded set of practices.

PMID- 24853532
TI  - A single-step approach to the diagnosis of primary hyperaldosteronism: filling a
      true void or burdening the bottleneck of adrenal vein sampling?

PMID- 24853533
TI  - Emotional vitality in family caregivers: content validation of a theoretical
      framework.
AB  - PURPOSE: Emotional vitality may play an important role in determining whether
      informal caregivers are able to successfully adopt and persist in their roles.
      This study describes a content validation of a conceptual model of emotional
      vitality in informal caregivers. METHODS: A secondary content analysis was
      performed on transcripts of 30 caregivers who were interviewed about their
      quality of life in relation to assuming the role of informal caregiver for a
      family member who had experienced a recent stroke. Caregivers discussed changes
      in their own health, relationships, roles, finances, participation, and mood
      after assuming the caregiving role. Using a thematic inductive approach, two
      raters independently coded the presence and frequency of physical, emotional, and
      social impacts associated with the caregiving role in order to further develop
      and validate a conceptual model of caregiver emotional vitality. RESULTS: The
      interviews provided information that affirmed the relevance of four themes
      relevant to caregiver emotional vitality previously identified: physical health
      and well-being; mood regulation; sense of control/mastery of new skills; and
      participation in meaningful activity. An additional theme of support and
      recognition from others also emerged. CONCLUSIONS: Adopting the informal
      caregiving role results in major impacts to the caregiver's physical, emotional,
      and social health. Five core domains appear to meaningfully contribute to
      emotional vitality of caregivers and may influence their ability to persist in
      this role over time. Many of the factors that influence emotional vitality in
      caregivers are potentially modifiable. This new model offers new opportunities
      for rehabilitation specialists and allied health professionals to develop skill
      building interventions that may help caregivers successfully adapt and thrive in
      the caregiving role.

PMID- 24853535
TI  - Effects of distinctive encoding on correct and false memory: a meta-analytic
      review of costs and benefits and their origins in the DRM paradigm.
AB  - We review and meta-analyze how distinctive encoding alters encoding and retrieval
      processes and, thus, affects correct and false recognition in the Deese-Roediger
      McDermott (DRM) paradigm. Reductions in false recognition following distinctive
      encoding (e.g., generation), relative to a nondistinctive read-only control
      condition, reflected both impoverished relational encoding and use of a retrieval
      based distinctiveness heuristic. Additional analyses evaluated the costs and
      benefits of distinctive encoding in within-subjects designs relative to between
      group designs. Correct recognition was design independent, but in a within
      design, distinctive encoding was less effective at reducing false recognition for
      distinctively encoded lists but more effective for nondistinctively encoded
      lists. Thus, distinctive encoding is not entirely "cost free" in a within design.
      In addition to delineating the conditions that modulate the effects of
      distinctive encoding on recognition accuracy, we discuss the utility of using
      signal detection indices of memory information and memory monitoring at test to
      separate encoding and retrieval processes. 

PMID- 24853536
TI  - The cost of blocking the mirror generalization process in reading: evidence for
      the role of inhibitory control in discriminating letters with lateral mirror
      image counterparts.
AB  - Mirror generalization is detrimental for identifying letters with lateral mirror
      image counterparts ('b/d'). In the present study, we investigated whether the
      discrimination of this type of letters in expert readers might be rooted in the
      ability to inhibit the mirror-generalization process. In our negative priming
      paradigm, participants judged whether two letters were identical on the prime and
      two animals (or buildings) were identical on the probe. In Experiment 1,
      participants required more time when determining that two animals (but not two
      buildings) were mirror images of each other when preceded by letters with mirror
      image counterparts than without mirror-image counterparts ('a/h'). In Experiment
      2, we replicated the results with different letters without mirror-image
      counterparts and with the type of probe stimuli (animal or building) manipulated
      as a within-subject factors. Our results suggest that expert readers never
      completely "unlearn" the mirror-generalization process and still need to inhibit
      this heuristic to overcome mirror errors. 

PMID- 24853537
TI  - Trichuris colobae n. sp. (Nematoda: Trichuridae), a new species of Trichuris from
      Colobus guereza kikuyensis.
AB  - In the present work, a morphological and biometrical study of whipworms Trichuris
      Roederer, 1761 (Nematoda: Trichuridae) parasitizing Colobus guereza kikuyensis
      has been carried out. Biometrical and statistical data showed that the mean
      values of individual variables between Trichuris suis and Trichuris sp. from C.
      g. kikuyensis differed significantly (P < 0.001) when Student's t test was
      performed: seven male variables (width of esophageal region of body, maximum
      width of posterior region of body, width in the place of junction of esophagus
      and the intestine, length of bacillary stripes, length of spicule, length of
      ejaculatory duct, and distance between posterior part of testis and tail end of
      body) and three female variables (width of posterior region of body, length of
      bacillary stripes, and distance of tail end of body and posterior fold of seminal
      receptacle). The combination of these characters permitted the discrimination of
      T. suis with respect to Trichuris sp. from C. g. kikuyensis, suggesting a new
      species of Trichuris. Furthermore, males of Trichuris sp. from C. g. kikuyensis
      showed a typical subterminal pericloacal papillae associated to a cluster of
      small papillae that were absent in males of T. suis, while females of Trichuris
      from Colobus appeared with a vulval region elevated/over-mounted showing a crater
      like appearance. The everted vagina showed typical triangular sharp spines by
      optical microscopy and SEM. Thus, the existence of a new species of Trichuris
      parasitizing C. g. kikuyensis has been proposed. 

PMID- 24853539
TI  - Fecal microbiota transplantation in children with recurrent Clostridium difficile
      infection.
AB  - Clostridium difficile eradication using fecal microbiota transplantation (FMT)
      has been successful in adults but little information is available in pediatrics.
      We report 6 pediatric patients with refractory C. difficile cured by FMT with no
      recurrences to date. Our results demonstrate that FMT can be an effective
      treatment for refractory C. difficile infection in pediatrics. Long-term safety
      and efficacy need to be studied. 

PMID- 24853538
TI  - Sublethal effects of atrazine and glyphosate on life history traits of Aedes
      aegypti and Aedes albopictus (Diptera: Culicidae).
AB  - Although exposure of mosquito larvae to agricultural chemicals such as herbicides
      is common and widespread, our understanding of how these chemicals affect
      mosquito ecology and behavior is limited. This study investigated how an
      environmentally relevant concentration of two herbicides, atrazine and
      glyphosate, affects mosquito life history traits. One hundred and fifty (150)
      first instar Aedes (Stegomyia) aegypti (L.) or Aedes (Stegomyia) albopictus
      (Skuse) larvae were reared in 1.6 L of live oak leaf (Quercus virginiana)
      infusion in the presence (5 mg/L) or absence (0 mg/L) of atrazine or glyphosate.
      The containers were monitored daily to determine the emergence rates, sex ratio,
      male and female emergence times, and female body size. Emergence rates of A.
      aegypti from atrazine treatment were significantly higher relative to either
      glyphosate or control treatments (A. aegypti: atrazine = 93 +/- 6% (+/-95% CI),
      glyphosate = 82 +/- 5%, control = 78 +/- 5%), while emergence rates of A.
      albopictus in atrazine treatments were significantly higher than in glyphosate
      treatments but not in controls (A. albopictus: atrazine = 84 +/- 5 %, glyphosate
      = 76 +/- 4%, control = 78 +/- 4%). For both mosquito species, a sex ratio
      distortion with male bias was observed in control and glyphosate treatments, but
      not in atrazine treatments (A. aegypti: atrazine = 0.90 +/- 0.17 (+/-SE),
      glyphosate = 1.63 +/- 0.21, control = 1.69 +/- 0.26; A. albopictus: atrazine =
      1.09 +/- 0.08, glyphosate = 1.88 +/- 0.12, control = 1.37 +/- 0.11). Emergence
      times for both sexes of the two mosquito species were significantly longer in
      atrazine treatments compared to glyphosate or control treatments (A. aegypti:
      females: atrazine = 11.20 +/- 0.50 (days +/- 95 % CI), glyphosate = 9.71 +/-
      0.23, control = 9.87 +/- 0.21; males: atrazine = 9.46 +/- 0.27, glyphosate = 8.80
      +/- 0.25, control = 8.85 +/- 0.24; A. albopictus: females: atrazine = 17.40 +/-
      1.70, glyphosate = 12.4 +/- 0.40, control = 12.5 +/- 0.30; males: atrazine =
      12.96 +/- 0.41, glyphosate = 10.48 +/- 0.24, control = 10.64 +/- 0.37). For A.
      albopictus but not A. aegypti, adult females from atrazine treatment had
      significantly longer wing lengths compared to those from glyphosate or control
      treatments (A. albopictus: atrazine = 3.06 +/- 0.07 (mm +/- 95% CI), glyphosate =
      2.80 +/- 0.07, control = 2.83 +/- 0.06). These results demonstrate the potential
      for atrazine, a widely used herbicide, to influence epidemiologically relevant
      life history traits of mosquitoes.

PMID- 24853540
TI  - Risk factors for infectious disease death among infants in the United States.
AB  - BACKGROUND: Infectious diseases (IDs) are an important cause of infant mortality
      in the United States. This study describes maternal and infant characteristics
      associated with infant ID deaths in the United States. METHODS: Infant deaths
      with an ID underlying cause of death occurring in the United States were examined
      using the 2008-2009 Period Linked Birth/Infant Death public use data files.
      Average annual ID infant mortality rates for singleton infants were calculated. A
      retrospective case-control study was conducted to determine infant and maternal
      risk factors for infant ID death among low (LBW) and normal (NBW) birth weight
      groups. Controls were defined as infants surviving to the end of their birth
      year. Risk factors for infant ID deaths were determined through multivariable
      logistic regression. RESULTS: An estimated 3843 infant ID deaths occurred in the
      United States during 2008-2009, an overall ID infant mortality rate of 47.5
      deaths per 100,000 live births. The mortality rate for LBW and NBW infants were
      514.8 and 15.5, respectively. Male sex, younger maternal age (<25 years), a live
      birth order of fourth or more and low 5-minute Apgar score were associated with
      increased ID death among LBW and NBW infants. Additionally, black maternal race
      was associated with increased ID death among LBW infants, and having an unmarried
      mother was associated with increased ID death among NBW infants. CONCLUSIONS:
      Awareness of associations with infant ID death should help in development of
      further strategic measures to reduce infant ID morbidity and mortality.

PMID- 24853541
TI  - Two cases of neonatal human parechovirus 3 encephalitis.
AB  - We report 2 neonates with human parechoviruses type 3 encephalitis. Both newborns
      presented with fever, irritability and seizures. Cerebrospinal fluid analyses
      were normal, but magnetic resonance imaging revealed white matter damage,
      suggesting human parechoviruse infection. Human parechoviruses type 3-RNA was
      detected in cerebrospinal fluid samples and in blood, stool, urine and
      respiratory samples, indicating the dissemination of the virus. 

PMID- 24853542
TI  - Murine typhus associated with Parinaud's oculoglandular syndrome in 2 children.
AB  - An 11-year-old-girl and a 13-year-old-boy presented with characteristic findings
      of Parinaud's oculoglandular syndrome. The girl was initially suspected of having
      Bartonella henselae infection and the boy was initially diagnosed as Francisella
      tularensis infection. Both children had laboratory-confirmed infection with
      Rickettsia typhi. 

PMID- 24853543
TI  - Acute transverse myelitis complicating breakthrough varicella infection.
AB  - We report a 10-year-old girl who presented with acute transverse myelitis after
      breakthrough varicella infection. The diagnosis was based on the development of
      motor weakness, paraparesis and bladder dysfunction, spinal magnetic resonance
      imaging findings and detection of anti-varicella zoster virus IgG antibody in the
      cerebrospinal fluid. This case report highlights that breakthrough varicella can
      result in serious complications such as acute transverse myelitis. 

PMID- 24853544
TI  - Mechanism for prevention of infection in preterm neonates by topical emollients:
      a randomized, controlled clinical trial.
AB  - BACKGROUND: Topical applications of emollients such as sunflower seed oil and
      Aquaphor have been shown to reduce the incidence of bloodstream infections and
      mortality of preterm infants in resource-poor settings. The causal mechanism for
      prevention of infection through cutaneous portals of entry is not well
      understood. METHODS: We examined the relationship between skin condition score as
      a measure of skin barrier integrity and risk for bloodstream infection, and the
      effect of emollients on that relationship. Data for this study come from a
      randomized controlled trial of the impact of topical emollient therapy on
      nosocomial infections in 491 preterm infants <33 weeks gestational age at Dhaka
      Shishu Hospital, Bangladesh. Latent growth trajectory model with random
      coefficient and multivariable logistic regression were utilized. RESULTS: Rate of
      deterioration of skin condition was significantly lower (P < 0.05) in both
      emollient arms compared with the untreated control group. Adjusted odds ratio of
      skin score for infection was 1.32 (95% confidence interval: 1.06-1.65).
      Emollients reduced the incidence of infection only when the skin had no signs of
      deterioration [Aquaphor incidence rate ratio: 0.43 (95% confidence interval: 0.19
      0.97) and sunflower seed oil incidence rate ratio: 0.46 (95% confidence interval:
      0.21-0.99)]. CONCLUSION: Skin condition deteriorated progressively after birth
      and compromised skin condition increased the risk of infection. Emollients
      preserved skin integrity and thus prevented infection in preterm neonates. To
      optimize benefits of emollients for the prevention of bloodstream infection, use
      of emollients should begin immediately after birth when the skin is still intact.

PMID- 24853545
TI  - Capillary-wall collagen as a biophysical marker of nanotherapeutic permeability
      into the tumor microenvironment.
AB  - The capillary wall is the chief barrier to tissue entry of therapeutic
      nanoparticles, thereby dictating their efficacy. Collagen fibers are an important
      component of capillary walls, affecting leakiness in healthy or tumor
      vasculature. Using a computational model along with in vivo systems, we compared
      how collagen structure affects the diffusion flux of a 1-nm chemotherapeutic
      molecule [doxorubicin (DOX)] and an 80-nm chemotherapy-loaded pegylated liposome
      (DOX-PLD) in tumor vasculature. We found a direct correlation between the
      collagen content around a tumor vessel to the permeability of that vessel
      permeability to DOX-PLD, indicating that collagen content may offer a biophysical
      marker of extravasation potential of liposomal drug formulations. Our results
      also suggested that while pharmacokinetics determined the delivery of DOX and DOX
      PLD to the same tumor phenotype, collagen content determined the extravasation of
      DOX-PLD to different tumor phenotypes. Transport physics may provide a deeper
      view into how nanotherapeutics cross biological barriers, possibly helping
      explain the balance between biological and physical aspects of drug delivery.

PMID- 24853547
TI  - Mechanisms of resistance to intermittent androgen deprivation in patients with
      prostate cancer identified by a novel computational method.
AB  - For progressive prostate cancer, intermittent androgen deprivation (IAD) is one
      of the most common and effective treatments. Although this treatment is usually
      initially effective at regressing tumors, most patients eventually develop
      castration-resistant prostate cancer (CRPC), for which there is no effective
      treatment and is generally fatal. Although several biologic mechanisms leading to
      CRPC development and their relative frequencies have been identified, it is
      difficult to determine which mechanisms of resistance are developing in a given
      patient. Personalized therapy that identifies and targets specific mechanisms of
      resistance developing in individual patients is likely one of the most promising
      methods of future cancer therapy. Prostate-specific antigen (PSA) is a biomarker
      for monitoring tumor progression. We incorporated a cell death rate (CDR)
      function into a previous dynamical PSA model that was highly accurate at fitting
      clinical PSA data for 7 patients. The mechanism of action of IAD is largely
      induction of apoptosis, and each mechanism of resistance varies in its CDR
      dynamics. Thus, we analyze the CDR levels and their time-dependent oscillations
      to identify mechanisms of resistance to IAD developing in individual patients.

PMID- 24853546
TI  - NDY1/KDM2B functions as a master regulator of polycomb complexes and controls
      self-renewal of breast cancer stem cells.
AB  - The JmjC domain histone H3K36me2/me1 demethylase NDY1/KDM2B is overexpressed in
      various types of cancer. Here we show that knocking down NDY1 in a set of 10 cell
      lines derived from a broad range of human tumors inhibited their anchorage
      dependent and anchorage-independent growth by inducing senescence and/or
      apoptosis in some and by inhibiting G1 progression in all. We further show that
      the knockdown of NDY1 in mammary adenocarcinoma cell lines decreased the number,
      size, and replating efficiency of mammospheres and downregulated the stem cell
      markers ALDH and CD44, while upregulating CD24. Together, these findings suggest
      that NDY1 is required for the self-renewal of cancer stem cells and are in
      agreement with additional findings showing that tumor cells in which NDY1 was
      knocked down undergo differentiation and a higher number of them is required to
      induce mammary adenocarcinomas, upon orthotopic injection in animals.
      Mechanistically, NDY1 functions as a master regulator of a set of miRNAs that
      target several members of the polycomb complexes PRC1 and PRC2, and its knockdown
      results in the de-repression of these miRNAs and the downregulation of their
      polycomb targets. Consistent with these observations, NDY1/KDM2B is expressed at
      higher levels in basal-like triple-negative breast cancers, and its
      overexpression is associated with higher rates of relapse after treatment. In
      addition, NDY1-regulated miRNAs are downregulated in both normal and cancer
      mammary stem cells. Finally, in primary human breast cancer, NDY1/KDM2B
      expression correlates negatively with the expression of the NDY1-regulated miRNAs
      and positively with the expression of their PRC targets.

PMID- 24853548
TI  - Mitochondrial retrograde signaling mediated by UCP2 inhibits cancer cell
      proliferation and tumorigenesis.
AB  - Cancer cells tilt their energy production away from oxidative phosphorylation
      (OXPHOS) toward glycolysis during malignant progression, even when aerobic
      metabolism is available. Reversing this phenomenon, known as the Warburg effect,
      may offer a generalized anticancer strategy. In this study, we show that
      overexpression of the mitochondrial membrane transport protein UCP2 in cancer
      cells is sufficient to restore a balance toward oxidative phosphorylation and to
      repress malignant phenotypes. Altered expression of glycolytic and oxidative
      enzymes mediated the effects of this metabolic shift. Notably, UCP2
      overexpression increased signaling from the master energy-regulating kinase,
      adenosine monophosphate-activated protein kinase, while downregulating expression
      of hypoxia-induced factor. In support of recent new evidence about UCP2 function,
      we found that UCP2 did not function in this setting as a membrane potential
      uncoupling protein, but instead acted to control routing of mitochondria
      substrates. Taken together, our results define a strategy to reorient
      mitochondrial function in cancer cells toward OXPHOS that restricts their
      malignant phenotype.

PMID- 24853550
TI  - When is a biopsy-proven diagnosis necessary before stereotactic ablative
      radiotherapy for lung cancer?: A decision analysis.
AB  - BACKGROUND: The practice of treating a solitary pulmonary nodule (SPN) suspicious
      for stage I non-small cell lung cancer (NSCLC) with stereotactic ablative
      radiotherapy (SABR) in the absence of pathology is growing. In the absence of
      randomized evidence, the appropriate prior probability threshold of lung cancer
      of when such a strategy is warranted can be informed using decision analysis.
      METHODS: A decision tree and Markov model were constructed to evaluate the
      relative merits of surveillance, a PET scan-directed SABR strategy (without
      pathology), or a PET scan-biopsy-SABR strategy, when faced with an SPN at
      different prior probabilities for lung cancer. Diagnostic characteristics, as
      well as disease, treatment, and toxicity parameters, were extracted from the
      literature. Deterministic analysis and probabilistic sensitivity analyses were
      performed to inform the appropriate lung cancer prior probability threshold
      between treatment strategies. RESULTS: In the reference case analysis, the prior
      probability threshold between surveillance and PET scan-biopsy-SABR was 17.0%;
      between PET scan-directed SABR and PET scan-biopsy-SABR, the threshold was 85.0%.
      The latter finding was confirmed on probabilistic sensitivity analysis (85.2%;
      95% CI, 80.0% to 87.2%). This predicted lung cancer prior probability threshold
      was most sensitive to the diagnostic sensitivity of transthoracic biopsy (range,
      77.2% to 94.0%) and the detection rate of false negatives on CT scan surveillance
      (range, 82.4% to 92.3%). CONCLUSIONS: This model suggests that if there are
      concerns about morbidity related to biopsy for an SPN, a PET scan-directed SABR
      strategy is warranted when the prior probability of lung cancer exceeds a point
      estimate of 85%.

PMID- 24853551
TI  - Carbon nanotube translocation to distant organs after pulmonary exposure:
      insights from in situ (14)C-radiolabeling and tissue radioimaging.
AB  - Few approaches are available to investigate the potential of carbon nanotubes
      (CNTs) to translocate to distant organs following lung exposure, although this
      needs to be taken into account to evaluate potential CNT toxicity. Here, we
      report a method for quantitative analysis of the tissue biodistribution of
      multiwalled CNTs (MWCNTs) as a function of time. The method relies on the use of
      in situ (14)C-radiolabeled MWCNTs and combines radioimaging of organ tissue
      sections to ex vivo analysis of MWCNTs by electron microscopy. To illustrate the
      usefulness of this approach, mice were exposed to a single dose of 20 MUg of
      (14)C-labeled MWCNTs by pharyngeal aspiration and were subjected to a follow-up
      study over one year. After administration, MWCNT were cleared from the lungs, but
      there was a concomitant relocation of these nanoparticles to distant organs
      starting throughout the follow-up period, with nanoparticle accumulation
      increasing with time. After one year, accumulation of MWCNTs was documented in
      several organs, including notably the white pulp of the spleen and the bone
      marrow. This study shows that the proposed method may be useful to complement
      other approaches to address unresolved toxicological issues associated with CNTs.
      These issues include their persistence over long periods in extrapulmonary
      organs, the relationship between the dose and the extent of translocation, and
      the effects of "safety by design" on those processes. The same approach could be
      used to study the translocation propensity of other nanoparticles containing
      carbon atoms. 

PMID- 24853549
TI  - Telomere length in white blood cell DNA and lung cancer: a pooled analysis of
      three prospective cohorts.
AB  - We investigated the relationship between telomere length and lung cancer in a
      pooled analysis from three prospective cohort studies: the Prostate, Lung,
      Colorectal and Ovarian (PLCO) Cancer Screening Trial, conducted among men and
      women in the United States, and previously published data from the Alpha
      Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Trial conducted among male
      smokers in Finland, and the Shanghai Women's Health Study (SWHS), which is
      comprised primarily of never-smokers. The pooled population included 847 cases
      and 847 controls matched by study, age, and sex. Leukocyte telomere length was
      measured by a monochrome multiplex qPCR assay. We used conditional logistic
      regression models to calculate ORs and their 95% confidence intervals (CI) for
      the association between telomere length and lung cancer risk, adjusted for age
      and pack-years of smoking. Longer telomere length was associated with increased
      lung cancer risk in the pooled analysis [OR (95% CI) by quartile: 1.00; 1.24
      (0.90-1.71); 1.27 (0.91-1.78); and 1.86 (1.33-2.62); P trend = 0.000022].
      Findings were consistent across the three cohorts and strongest for subjects with
      very long telomere length, i.e., lung cancer risks for telomere length [OR (95%
      CI)] in the upper half of the fourth quartile were 2.41 (1.28-4.52), 2.16 (1.11
      4.23), and 3.02(1.39-6.58) for the PLCO trial, the ATBC trial, and the SWHS,
      respectively. In addition, the association persisted among cases diagnosed more
      than 6 years after blood collection and was particularly evident for female
      adenocarcinoma cases. Telomere length in white blood cell DNA may be a biomarker
      of future increased risk of lung cancer in diverse populations.

PMID- 24853552
TI  - Food protein-induced enterocolitis syndrome: pitfalls in the diagnosis.
AB  - Food protein-induced enterocolitis syndrome (FPIES) represents the severe end of
      the spectrum of gastrointestinal food hypersensitivity; its acute episodes can
      culminate in severe dehydration and hypovolemic shock, and its chronic form
      entails considerable morbidity associated with feeding difficulty and failure to
      thrive. Nevertheless, awareness for this syndrome remains rather low. Many
      factors hamper the establishment of FPIES diagnosis. Such factors pertain to the
      pathophysiological mechanism of the syndrome, causal food proteins, clinical
      manifestations, diagnostic procedures, differential diagnosis considerations, and
      prevailing perceptions which may require critical appraisal. Throughout this
      review, we will present and discuss these issues and put the focus on factors
      that could lead to under-diagnosis of FPIES, cause numerous acute episodes, and
      substantially increase the diseases morbidity and financial burden. We will also
      address other issues that are clinically relevant to FPIES. 

PMID- 24853553
TI  - A cross-sectional survey among patients and prescribers on insulin dosing
      irregularities and impact of mild (self-treated) hypoglycemia episodes in Spanish
      patients with type 2 diabetes as compared to other European patients.
AB  - BACKGROUND AND OBJECTIVE: In Spain, data suggest that 13.8% of adults have
      diabetes. Two important aspects in diabetes management are mild hypoglycemic
      episodes and poor treatment adherence. This study assesses the impact of missed
      insulin doses and prevalence of mistimed and reduced insulin doses and mild
      hypoglycemia in patients with type 2 diabetes treated with basal insulin
      analogues in Spain, and compares the data collected to pooled data from 8 other
      European countries (OECs). MATERIALS AND METHODS: GAPP2 was an international,
      online, cross-sectional study of diabetic patients aged >=40 years treated with
      long-acting insulin analogues and their healthcare professionals. Patients and
      healthcare professionals were recruited from online research panels. Data
      reported in Spain are compared to pooled data from 8 OECs. RESULTS: In Spain, 1
      3% of patients reported they had reduced, missed, or mistimed at least one
      insulin does in the previous month. Significantly more OEC patients reported
      dosing irregularities (15-23%; all P<0.01). In Spain, 77% of patients were
      worried and 59% felt guilty for missing a dose of basal insulin, while 24%
      reported that they were very worried about nocturnal hypoglycemia. Significantly
      fewer OEC patients reported worrying (47%; P<0.01) and feeling guilty (37%;
      P<0.01) about missing an insulin dose, or worry about nocturnal hypoglycemia
      (12%; P<0.01). CONCLUSIONS: In Spain, patients with type 2 diabetes report fewer
      dosing irregularities and hypoglycemic episodes as compared to patients from
      OECs. However, Spanish patients appear to have a reduced quality of life related
      to hypoglycemia as well as worry and guilt related to insulin dosing
      irregularities.

PMID- 24853555
TI  - Natural infection of pregnant cows with Schmallenberg virus--a follow-up study.
AB  - Schmallenberg virus (SBV), an orthobunyavirus discovered in European livestock in
      late 2011 for the first time, causes premature or stillbirth and severe fetal
      malformation when cows and ewes are infected during pregnancy. Therefore, cattle
      of two holdings in the initially most affected area in Germany were closely
      monitored to describe the consequence for fetuses and newborn calves. Seventy-one
      calves whose mothers were naturally infected during the first five months of
      pregnancy were clinically, virologically, and serologically examined. One calve
      showed typical malformation, another one, born without visible abnormalities, was
      dead. Two cows aborted during the studied period; spleen and brain samples or
      meconium swabs were tested by real-time PCR, in none of the fetuses SBV-specific
      RNA was detectable and the tested fetal sera were negative in a commercially
      available antibody ELISA. In contrast, in nine clinically healthy calves high SBV
      antibody titers were measurable before colostrum intake, and in meconium swabs of
      six of these animals viral RNA was present as well. The mothers of all nine
      seropositive calves were presumably infected between days 47 and 162 of
      gestation, which is within the critical timeframe for fetal infection suggested
      for SBV and related viruses. 

PMID- 24853554
TI  - Quantifying and predicting the effect of exogenous interleukin-7 on CD4+ T cells
      in HIV-1 infection.
AB  - Exogenous Interleukin-7 (IL-7), in supplement to antiretroviral therapy, leads to
      a substantial increase of all CD4+ T cell subsets in HIV-1 infected patients.
      However, the quantitative contribution of the several potential mechanisms of
      action of IL-7 is unknown. We have performed a mathematical analysis of repeated
      measurements of total and naive CD4+ T cells and their Ki67 expression from HIV-1
      infected patients involved in three phase I/II studies (N = 53 patients). We show
      that, besides a transient increase of peripheral proliferation, IL-7 exerts
      additional effects that play a significant role in CD4+ T cell dynamics up to 52
      weeks. A decrease of the loss rate of the total CD4+ T cell is the most probable
      explanation. If this effect could be maintained during repeated administration of
      IL-7, our simulation study shows that such a strategy may allow maintaining CD4+
      T cell counts above 500 cells/uL with 4 cycles or fewer over a period of two
      years. This in-depth analysis of clinical data revealed the potential for IL-7 to
      achieve sustained CD4+ T cell restoration with limited IL-7 exposure in HIV-1
      infected patients with immune failure despite antiretroviral therapy. 

PMID- 24853557
TI  - The phytochrome B/phytochrome C heterodimer is necessary for phytochrome C
      mediated responses in rice seedlings.
AB  - BACKGROUND: PhyC levels have been observed to be markedly lower in phyB mutants
      than in Arabidopsis or rice wild type etiolated seedlings, but the mechanism of
      this phenomenon has not been fully elucidated. RESULTS: In the present study, we
      investigated the mechanism by which phyB affects the protein concentration and
      photo-sensing abilities of phyC and demonstrated that rice phyC exists
      predominantly as phyB/phyC heterodimers in etiolated seedlings. PHYC-GFP protein
      was detected when expressed in phyA phyC mutants, but not in phyA phyB mutants,
      suggesting that phyC requires phyB for its photo-sensing abilities.
      Interestingly, when a mutant PHYB gene that has no chromophore binding site,
      PHYB(C364A), was introduced into phyB mutants, the phyC level was restored.
      Moreover, when PHYB(C364A) was introduced into phyA phyB mutants, the seedlings
      exhibited de-etiolation under both far-red light (FR) and red light (R)
      conditions, while the phyA phyB mutants were blind to both FR and R. These
      results are the first direct evidence that phyC is responsible for regulating
      seedling de-etiolation under both FR and R. These findings also suggest that phyB
      is indispensable for the expression and function of phyC, which depends on the
      formation of phyB/phyC heterodimers. SIGNIFICANCE: The present report clearly
      demonstrates the similarities and differences in the properties of phyC between
      Arabidopsis and rice and will advance our understanding of phytochrome functions
      in monocots and dicots.

PMID- 24853560
TI  - Tyrosinase enzyme: 1. An overview on a pharmacological target.
AB  - The tyrosinase enzyme (EC 1.14.18.1) is an oxidoreductase inside the general
      enzyme classification and is involved in the oxidation and reduction process in
      the epidermis. These chemical reactions that the enzyme catalyzes are of
      principal importance in the melanogenesis process. This process of melanogenesis
      is related to the melanin formation, a heteropolymer of indolic nature that
      provides the different tonalities in the skin and helps to the protection from
      the ultraviolet radiation. However, a pigment overproduction, come up by the
      action of the tyrosinase, can cause different disorders in the skin related to
      the hyperpigmentation. Several studies mainly focused on the characteristics of
      the enzyme have been reported. In this work, an approximation to general aspects
      related to this enzyme is made. Besides, it is treated the researches that have
      been published in the part of the biochemical anatomy dealing with diseases
      associated with this protein (melanogenesis), its active place and its
      physiological states, the molecular mechanism, the methods carried out to detect
      the inhibitory activity, and the used substrates.

PMID- 24853558
TI  - Cigarette smoke-induced lung endothelial apoptosis and emphysema are associated
      with impairment of FAK and eIF2alpha.
AB  - Lung endothelial cell (EC) apoptosis has been implicated in the pathogenesis of
      emphysema. However, the mechanism underlying cigarette smoke (CS)-induced lung EC
      apoptosis and emphysema is not well defined. We have previously shown that
      cigarette smoke extract (CSE) decreased focal adhesion kinase (FAK) activity via
      oxidative stress in cultured lung EC. In this study, we compared FAK activation
      in the lungs of highly susceptible AKR mice and mildly susceptible C57BL/6 mice
      after exposure to CS for three weeks. We found that three weeks of CS exposure
      caused mild emphysema and increased lung EC apoptosis in AKR mice (room air:
      12.8+/-5.6%; CS: 30.7+/-3.7%), but not in C57BL/6 mice (room air: 0+/-0%; CS:
      3.5+/-1.7%). Correlated with increased lung EC apoptosis and early onset of
      emphysema, FAK activity was reduced in the lungs of AKR mice, but not of C57BL/6
      mice. Additionally, inhibition of FAK caused lung EC apoptosis, whereas over
      expression of FAK prevented CSE-induced lung EC apoptosis. These results suggest
      that FAK inhibition may contribute to CS-induced lung EC apoptosis and emphysema.
      Unfolded protein response (UPR) and autophagy have been shown to be activated by
      CS exposure in lung epithelial cells. In this study, we noted that CSE activated
      UPR and autophagy in cultured lung EC, as indicated by enhanced eIF2alpha
      phosphorylation and elevated levels of GRP78 and LC3B-II. However, eIF2alpha
      phosphorylation was significantly reduced by three-weeks of CS exposure in the
      lungs of AKR mice, but not of C57BL/6 mice. Markers for autophagy activation were
      not significantly altered in the lungs of either AKR or C57BL/6 mice. These
      results suggest that CS-induced impairment of eIF2alpha signaling may increase
      the susceptibility to lung EC apoptosis and emphysema. Taken together, our data
      suggest that inhibition of eIF2alpha and FAK signaling may play an important role
      in CS-induced lung EC apoptosis and emphysema.

PMID- 24853561
TI  - Flavonoid derivatives as potent tyrosinase inhibitors - a survey of recent
      findings between 2008-2013.
AB  - Tyrosinase (EC 1.14.18.1), also known as polyphenols oxidase, is a glycosylated
      multi-copper monooxygenase enzyme widely distributed in many different organisms.
      The enzyme is responsible for the pigmentation of skin, eyes and hair in mammals
      and in fruits and vegetables undesired browning. These issues have encouraged
      researchers all over the world to seek new, potent and safe inhibitors of the
      enzyme for use in foods and cosmetics. A large number of compounds from natural
      products have been reported as moderate to potent inhibitors of tyrosinase. Among
      them, many flavonoid derivatives have been revealed to be the strong inhibitors
      of tyrosinase. In this review, we reviewed many examples of tyrosinase inhibitors
      with flavonoid structure reported between 2008-2013. Our findings underline that
      flavonoids should continue to be the focus of tyrosinase inhibition studies as
      the promising compounds. 

PMID- 24853562
TI  - A rational workflow for sequential virtual screening of chemical libraries on
      searching for new tyrosinase inhibitors.
AB  - The tyrosinase is a bifunctional, copper-containing enzyme widely distributed in
      the phylogenetic tree. This enzyme is involved in the production of melanin and
      some other pigments in humans, animals and plants, including skin pigmentations
      in mammals, and browning process in plants and vegetables. Therefore, enzyme
      inhibitors has been under the attention of the scientist community, due to its
      broad applications in food, cosmetic, agricultural and medicinal fields, to avoid
      the undesirable effects of abnormal melanin overproduction. However, the research
      of novel chemical with antityrosinase activity demands the use of more efficient
      tools to speed up the tyrosinase inhibitors discovery process. This chapter is
      focused in the different components of a predictive modeling workflow for the
      identification and prioritization of potential new compounds with activity
      against the tyrosinase enzyme. In this case, two structure chemical libraries
      Spectrum Collection and Drugbank are used in this attempt to combine different
      virtual screening data mining techniques, in a sequential manner helping to avoid
      the usually expensive and time consuming traditional methods. Some of the
      sequential steps summarize here comprise the use of drug-likeness filters,
      similarity searching, classification and potency QSAR multiclassifier systems,
      modeling molecular interactions systems, and similarity/diversity analysis.
      Finally, the methodologies showed here provide a rational workflow for virtual
      screening hit analysis and selection as a promissory drug discovery strategy for
      use in target identification phase. 

PMID- 24853563
TI  - Novel pentapeptide activators of mammalian and mushroom tyrosinase.
AB  - Melanoma incidence continues to rise due to intentional exposure to ultraviolet
      radiation (UVR) from sunlight and indoor tanning beds. Eumelanin exhibits
      photoprotective effects; thus, agents that induce its synthesis offer a means for
      sunless tanning without UVR damage. Herein, we report the development of two
      pentapeptides, P9 and P10, capable of enhancing melanin synthesis in B16 melanoma
      cells by activating mushroom and mouse tyrosinases without any effect on cell
      viability or proliferation. P9 and P10 significantly increased melanin content in
      a dose-dependent manner comparable to the positive controls, IBMX, scoparone, and
      alpha-MSH. However, unlike IBMX and scoparone, but similar to alpha-MSH, P9 and
      P10 were able to reverse 6BH4-dependent tyrosinase inhibition. We hypothesize
      that P9 and P10 allosterically activate tyrosinase and consequently enhance
      epidermal melanin synthesis. P9 and P10 may offer an alternative to tanning bed
      use and non-photoprotective tanning products. Moreover, sustained increase of
      melanin content in skin has the potential to reduce symptoms of photosensitivity
      disorders such as erythropoietic protoporphyria (EPP), solar urticaria (SU) and
      polymorphic light eruption (PLE), which lack fully effective treatments and
      result in significant morbidity.

PMID- 24853559
TI  - PARP-1 Val762Ala polymorphism and risk of cancer: a meta-analysis based on 39
      case-control studies.
AB  - BACKGROUND: Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear chromatin
      associated enzyme involved in several important cellular processes, particularly
      in the DNA repair system. PARP-1 rs1136410: C>T is among the most studied
      polymorphisms and likely involved in human carcinogenesis. However, results from
      previous studies are inconclusive. Thus, a meta-analysis was conducted to derive
      a more precise estimation of the effects of this enzyme. METHODOLOGY AND
      PRINCIPAL FINDINGS: A comprehensive search was conducted in the PubMed and EMBASE
      databases until December 9, 2013. A total of 39 studies with 16,783 cancer cases
      and 23,063 control subjects were included in the meta-analysis on the basis of
      the inclusion and exclusion criteria. No significant association between the PARP
      1 Val762Ala polymorphism and cancer risk was found when all of the studies were
      pooled into the analysis (VA + AA vs. VV: OR = 1.03, 95% CI = 0.95-1.11). The
      subgroup analysis of cancer types revealed that the -762Ala allele was associated
      with increased risk of gastric, cervical, and lung cancers and a decreased risk
      of glioma. In addition, a significantly increased risk of cancer associated with
      the polymorphism was observed in Asian descendents (VA + AA vs. VV: OR = 1.17,
      95% CI = 1.09-1.25; AA vs. VV: OR = 1.28, 95% CI = 1.08-1.51; VA vs. VV: OR =
      1.12, 95% CI = 1.04-1.20; AA vs. VA + VV: OR = 1.09, 95% CI = 1.03-1.39). These
      results also indicated that a joint effect between PARP-1 Val762Ala and XRCC1
      Arg399Gln could be involved in the risk of cancer development (OR = 3.53, 95% CI
      = 1.30-9.59). CONCLUSION: The present meta-analysis provides evidence that the
      PARP-1 Val762Ala may be involved in cancer development at least in some ethnic
      groups (Asian) or some specific cancer types (gastric, cervical, and lung
      cancers, and glioma).

PMID- 24853564
TI  - Tyrosinase inhibitors from terrestrial and marine resources.
AB  - Tyrosinase is a multifunctional copper-containing enzyme widely distributed in
      plants and animals, which catalyzes both the hydroxylation of tyrosine into o
      diphenols and the oxidation of o-diphenols into o-quinones. Tyrosinase is known
      to be a key enzyme for melanin biosynthesis in plants and animals. Tyrosinase
      inhibitors, therefore, can be clinically useful for the treatment of some
      dermatological disorders associated with melanin hyperpigmentation. They also
      find uses in cosmetics for whitening and depigmentation after sunburn. This
      review describes 236 compounds obtained from terrestrial and marine plants,
      animals, microorganisms and macrofungi which have been shown to inhibit
      tyrosinase. The mechanism of action of tyrosinase, together with the mode of
      action of inhibitors is described. The relative activities of the different
      compounds are recorded. The literature on plant-origin inhibitors is extensive,
      and their chemistry and biological activity have been intensively reviewed. This
      review will therefore be deliberately cover new classes of inhibitors from
      terrestrial and marine plants, animals, microorganisms and macrofungi, as well as
      the traditional classes. The present paper summarizes and discusses the
      scientific results on the discovery of natural tyrosinase inhibitors.

PMID- 24853565
TI  - Editorial: Tyrosinase inhibitors - computational prediction, organic synthesis,
      isolation from natural sources and biological assay.

PMID- 24853567
TI  - Cow's milk allergy (CMA) in children: identification of allergologic tests
      predictive of food allergy.
AB  - Oral food challenge (OFC) is still considered the gold standard for diagnosis of
      food allergy (FA). Skin prick test (SPT) and specific IgE (sIgE) tests are very
      useful but limited in their predictive accuracy. End point test (EPT) has been
      recently considered to determine the starting dose to induce oral
      desensitization. Allergometric tests combined may discriminate children at higher
      risk of reactions during OFC. We considered 94 children referred to our Allergy
      and Immunology Pediatric Department between January 2009 and December 2011 with
      CMA. Cutaneous allergometric skin tests (SPT and EPT) were periodically performed
      on all 94 children with CMA; sIgE levels against cow's milk proteins (CMP) alpha
      lactalbumin, beta-lactoglobulin and casein were periodically evaluated through
      blood samples every 6-12 months. During the period of the study, 26/94 (27.6%)
      children underwent more than once OFC. We collected 135 OFC compared with
      clinical presentation: 49/135 (36.2%) OFC were performed shortly after the onset
      of symptoms directly related to spontaneous intake of milk, to confirm suspicion
      of FA; 86/135 (63.7%) OFC were performed to evaluate the acquisition of
      tolerance. Of these, 52/86 (60.4%) OFC resulted positive, 34/86 (39.5%) were
      negative. The 3D EPT has the best ratio sensitivity (SE) / positive predictive
      value (PPV), SE 83%, specificity (SP) 58.3%, PPV 89.3%, negative predictive value
      (NPV) 45.1%. EPT 6D and 7D have the best PPV (100%) with a low NPV (respectively
      22.2% and 21.2%). We obtained that a mean fresh milk wheal diameter >= 12 mm was
      predictive of 97% OFC, but only 32/101 (31.6%) allergic children presented this
      value. The tests with a wheal diameter <= 5 were performed on younger children,
      all of which were less than 9 months old; only 5 other tests performed on less
      than 9 months olds resulted in the others subgroups (1 in >= 12 mm wheal and 4 in
      the group between 6-11 mm). We also found that 95% of children with 4D EPT wheal
      diameter < 6 mm resulted tolerant. This cut off could be useful to decide which
      children have a lower risk of reactions during the OFC. EPT is more useful than
      SPT especially for children < 1 year of age being a less operator dependent test,
      and it could be helpful to discriminate between children with the highest risk to
      develop anaphylaxis following an OFC (>= 5D positive EPT) and children with
      lowest risk (> 2D positive EPT), but it can't replace OFC, that currently remains
      the gold standard in the diagnosis of FA. We also underline that in allergic
      children younger than 9 months old, the values of SPT with fresh milk is much
      lower than in older children, so that it's better to separate this group of age
      when we try to predict the evolution of OFC through the evaluation with EPT. A
      validation of such results in a prospective study could maybe be useful to
      confirm the outcome of our data in the predictivity of OFC. 

PMID- 24853566
TI  - Psychosocial factors and medication adherence among patients with coronary heart
      disease: A text messaging intervention.
AB  - OBJECTIVE: Medication adherence is a complex behavior that is influenced by
      numerous factors. Applying self-efficacy theory, the primary aim of this
      randomized controlled trial was to compare medication self-efficacy among
      patients with coronary heart disease who received: (a) text messages (TMs) for
      medication reminders and education, (b) TMs for education, or (c) no TMs. The
      second aim was to identify the personal (sociodemographic and clinical
      characteristics) and psychosocial factors that were associated with and predicted
      medication adherence. METHODS: Customized TMs were delivered over 30 days.
      Repeated measures analysis of variance was used to analyze medication self
      efficacy. A multiple regression analysis was performed at baseline and follow-up
      to determine variables that were associated with and predicted self-reported
      medication adherence. RESULTS: Among 90 subjects with mean age 59.2 years
      (standard deviation (SD) 9.4, range 35-83), total scores for medication self
      efficacy improved over 30 days; however, there was no significant difference in
      this improvement as a function of the different treatment groups (p=0.64).
      Controlling for other variables in the model (age, education, depression, and
      social support), less depression (p=0.004) and higher social support (p=0.02)
      positively predicted higher medication adherence in the final model. CONCLUSIONS:
      TM medication reminders and/or health education did not improve medication self
      efficacy. Further theory testing of current and future models and interventions
      are required to understand variables related to self-efficacy and medication
      adherence. Addressing psychosocial factors such as depression and social support
      should be a priority to improve medication adherence among patients with coronary
      heart disease.

PMID- 24853568
TI  - Component resolved diagnosis (CRD): how much is it presently used by Italian
      allergists?
AB  - Component resolved diagnosis (CRD) represents an innovative and revolutionary
      tool in allergy diagnosis. At the same time, some criticisms can be outlined. The
      present web survey aimed at investigating the role of CRD in daily clinical
      practice, according to a sample of Italian specialists who manage allergic
      patients. 127 physicians, mostly allergists, completed the questionnaire, mainly
      coming from North and Center of Italy. Most of them (80%) were allergists. One
      physician out of three regularly takes into consideration CRD, that is currently
      available about in a half of the hospitals where the specialists work. CRD is
      mostly prescribed in the diagnostic work-up of suspected food allergy, as it can
      drive risk assessment, epinephrine prescription and dietary advice. Concerning
      respiratory allergy, CRD is considered useful in investigating cross-reactivity
      and in defining the best treatment option, even if only 32% of patients treated
      with immunotherapy had been previously studied with CRD. The present survey
      points out the need for the specialists to develop a more practical know-how
      about CRD. Its diagnostic accuracy and its real impact on the clinical management
      need to be better defined. The lacking of CRD technology in many hospitals limits
      the possibility for many allergists to directly experience molecular diagnosis. 

PMID- 24853569
TI  - Relationship between Methacholine Challenge Testing and exhaled nitric oxide in
      adult patients with suspected bronchial asthma.
AB  - Usually, hyperresponsiveness to inhaled methacholine is considered closely
      associated with a diagnosis of bronchial asthma. Recently, it has been clearly
      pointed out that bronchial hyperreactivity (BHR) is not a constant feature of
      asthma and that this condition is not always related to airways inflammation. In
      the present study we evaluated 42 Patients (21 positive and 21 negative for
      bronchial hyperreactivity, BHR) with the aim to determine the effect of
      Methacholine Challenge Testing (MCT) on the levels of exhaled nitric oxide (NO).
      Higher FeNO levels were found before methacholine provocation in the group that
      eventually resulted positive to the challenge, while after the challenge in both
      groups FeNO decreased in similar way, with no statistical difference. These data
      confirm that MCT is a relevant test for asthma diagnosis, but it is not always
      related to the severity of bronchial inflammation, while FeNO levels in our study
      have limited clinical significance when evaluated out of asthma exacerbation. 

PMID- 24853570
TI  - Psychiatric adverse reaction induced by clarithromycin.

PMID- 24853571
TI  - Adverse reaction to sublingual Parietaria vaccine following an ultra-rush
      induction.
AB  - In the treatment of respiratory allergies Sublingual Immunotherapy (SLIT)
      represents a valid alternative to Subcutaneous Immunotherapy (SCIT) for its
      better safety profile. We describe a case of acute severe asthma following the
      first maintenance dose of SLIT in a boy allergic to Parietaria pollen. At the
      initiation of therapy, the patient was in healthy condition and his asthma
      appeared to be under control. An ultra-rush induction had given no reaction.
      Despite the good safety profile of SLIT, clinicians should be aware of the risk
      of adverse effects when prescribing SLIT for respiratory allergies. 

PMID- 24853572
TI  - Iatrogenic angioedema associated with ACEi, sitagliptin, and deficiency of 3
      enzymes catabolizing bradykinin.
AB  - New concepts of idiopathic and iatrogenic angioedema underline the role of
      bradykinin, and the importance of catabolizing enzymes. A case is described of
      Angiotensin converting enzyme inhibitor (ACEi) and sitagliptin induced
      angioedema, where AO attacks decreased after the withdrawal of lisinopril but
      resolved only after the withdrawal of sitagliptin, an inhibitor of
      dipeptylpeptidase IV. ACE, aminopeptidase P and carboxypeptidase N were decreased
      down to 17%, 42%, 64% of median references values, and remained low one year
      after the interruption of these drugs: 56%, 28% and 50%, respectively. The
      combined deficiency of APP and CPN might enhance the inhibiting effect of the DPP
      IV inhibitor. The fact that this triple deficiency remained latent before and
      after the treatment indicates that searching for latent enzyme deficiencies
      should be carried out when there is intention to treat with a combination of
      drugs interfering with the bradykinin metabolism. 

PMID- 24853573
TI  - Anaphylactic shock to raspberry.

PMID- 24853574
TI  - Comments on: "allergen immunotherapy as a drug: the new deal of grass allergen
      tablets from clinical trials to current practice".

PMID- 24853575
TI  - Reply: To PMID 23821831.

PMID- 24853576
TI  - Total synthesis of the bacillosamine containing alpha-l-serine linked
      trisaccharide of Neisseria meningitidis.
AB  - Total synthesis of the bacillosamine containing l-serine linked O-trisaccharide
      of Neisseria meningitidis is described. The synthesis entails installation of two
      consecutive alpha-linkages including the coupling of bacillosamine with l-serine
      derivative. 

PMID- 24853578
TI  - Comparison between Solanum torvum Sw. and S. melongena L. after Ralstonia
      solanacearum inoculation.
AB  - Bacterial wilt, caused by Ralstonia solanacearum, is one of the most devastating
      plant diseases, affecting some economically important Solanaceae crops. In
      contrast, Solanum torvum, also known as wild eggplant, does not wilt when
      infested with R. solanacearum. In order to describe the mechanism underlying the
      response of S. torvum, it was compared with the cultivated eggplant, S.
      melongena, when both were infected with the same R. solanacearum strain. No
      wilting occurred in S. torvum, although the bacteria colonised roots and stems in
      both species within the first 24 h. There were marked differences beyond 24 h,
      consisting of high bacterial mortality in S. torvum. Using the calli model, our
      investigations revealed an increase in cell wall monoamine oxidase activity in S.
      torvum after R. solanacearum inoculation, which did not occur in S. melongena.

PMID- 24853577
TI  - O-2050 facilitates noradrenaline release and increases the CB1 receptor inverse
      agonistic effect of rimonabant in the guinea pig hippocampus.
AB  - The cannabinoid CB1 receptors on the noradrenergic neurons in guinea pig
      hippocampal slices show an endogenous endocannabinoid tone. This conclusion is
      based on rimonabant, the facilitatory effect of which on noradrenaline release
      might be due to its inverse CB1 receptor agonism and/or the interruption of a
      tonic inhibition elicited by endocannabinoids. To examine the latter mechanism, a
      neutral antagonist would be suitable. Therefore, we studied whether O-2050 is a
      neutral CB1 receptor antagonist in the guinea pig hippocampus and whether it
      mimics the facilitatory effect of rimonabant. CB1 receptor affinity of O-2050 was
      quantified in cerebrocortical membranes, using (3)H-rimonabant binding. Its CB1
      receptor potency and effect on (3)H-noradrenaline release were determined in
      superfused hippocampal slices. Its intrinsic activity at CB1 receptors was
      studied in hippocampal membranes, using (35)S-GTPgammaS binding. Endocannabinoid
      levels in hippocampus were determined by liquid chromatography-multiple reaction
      monitoring. O-2050 was about ten times less potent than rimonabant in its CB1
      receptor affinity, potency and facilitatory effect on noradrenaline release.
      Although not affecting (35)S-GTPgammaS binding by itself, O-2050 shifted the
      concentration-response curve of a CB1 receptor agonist to the right but that of
      rimonabant to the left. Levels of anandamide and 2-arachidonoyl glycerol in
      guinea pig hippocampus closely resembled those in mouse hippocampus. In
      conclusion, our results with O-2050 confirm that the CB1 receptors on
      noradrenergic neurons of the guinea pig hippocampus show an endogenous tone. To
      differentiate between the two mechanisms leading to an endogenous tone, O-2050 is
      not superior to rimonabant since O-2050 may increase the inverse agonistic effect
      of endocannabinoids.

PMID- 24853579
TI  - Renal insufficiency, mortality, and drug management in heart transplant. Results
      of the CARIN study.
AB  - Renal insufficiency (RI) is a frequent complication in heart transplant (HT)
      patients. The main objectives of the Cardiac trAnsplantation and Renal
      INsufficiency (CARIN) study were to follow the evolution of renal function after
      heart transplantation (HTx), to identify the factors associated with the decline
      of renal function, to describe the impact of RI on mortality during 3 years after
      the HT, and to observe the renal profile of the prescriptions. CARIN was a French
      retrospective, multicentric, study. Data were collected for patients who received
      a HT between 2000 and 2005. Data collection was performed at five time points:
      before HTx (T0), 1(T1), 6(T6), 12 (T12), and 36 (T36) months after HTx.
      Glomerular filtration rate (GFR) was estimated with aMDRD formula. RI was defined
      as GFR < 60 ml/min/1.73 m2. Four hundred and forty-one patients from five HT
      centers were included. The prevalences of RI were 28.8% (T0), 54.0% (T1), 50.4%
      (T6), 51.6% (T12), and 59.6% (T36). Age and cyclosporine were independently
      linked to the decline of renal function. Hypertension and GFR < 60 at T0 were
      independent risk factors of mortality. 48.7-64.7% of the nonimmunosuppressive
      prescriptions were drugs that required dosage adjustment in RI patients or for
      which no data were available concerning administration in RI patients. RI is
      highly frequent after HTx. Because RI is a risk factor of mortality, any sparing
      renal strategies have to be undertaken. 

PMID- 24853580
TI  - Metabolite profiles of epimedin C in rat plasma and bile by ultra-performance
      liquid chromatography coupled with quadrupole-TOF-MS.
AB  - Epimedin C is one of the major bioactive constituents of Herba Epimedii. In this
      study, the metabolite profiles of epimedin C in rat plasma and bile were
      qualitatively investigated, and the possible metabolic pathways of epimedin C
      were subsequently proposed. After oral administration of epimedin C at a single
      dose of 80 mg/kg, rat biological samples were collected and pretreated by protein
      precipitation. Then these pretreated samples were injected into an Acquity UPLC
      BEH C18 column and detected by ultra-performance liquid chromatography/quadrupole
      time-of-flight mass spectrometry. In all, 12 metabolites were identified in the
      biosamples. Of these, eight, two from plasma and six from bile, are, to our
      knowledge, reported here for the first time. The results indicated that epimedin
      C was metabolized via desugarization, dehydrogenation, hydrogenation,
      dehydroxylation, hydroxylation, demethylation and glucuronidation pathways in
      vivo. Thus, this study revealed the possible metabolite profiles of epimedin C in
      rat plasma and bile.

PMID- 24853581
TI  - Adults see vision to be more informative than it is.
AB  - Humans gain a wide range of knowledge through interacting with the environment.
      Each aspect of our perceptual experiences offers a unique source of information
      about the world-colours are seen, sounds heard and textures felt. Understanding
      how perceptual input provides a basis for knowledge is thus central to
      understanding one's own and others' epistemic states. Developmental research
      suggests that 5-year-olds have an immature understanding of knowledge sources and
      that they overestimate the knowledge to be gained from looking. Without evidence
      from adults, it is not clear whether the mature reasoning system outgrows this
      overestimation. The current study is the first to investigate whether an
      overestimation of the knowledge to be gained from vision occurs in adults. Novel
      response time paradigms were adapted from developmental studies. In two
      experiments, participants judged whether an object or feature could be identified
      by performing a specific action. Adult participants found it disproportionately
      easy to accept looking as a proposed action when it was informative, and
      difficult to reject looking when it was not informative. This suggests that
      adults, like children, overestimate the informativeness of vision. The origin of
      this overestimation and the implications that the current findings bear on the
      interpretation of children's overestimation are discussed. 

PMID- 24853582
TI  - Declining childhood and adolescent cancer mortality: great progress but still
      much to be done.

PMID- 24853583
TI  - Application of cyclodextrins in chiral capillary electrophoresis.
AB  - CE represents a very powerful separation tool in the area of chiral separations.
      CD-mediated chiral CE is a continuously flourishing technique within the frame of
      the electromigration methods. In this review, a brief overview of the synthetic
      procedures leading to modified CDs is provided first. Next, selected aspects
      related to the utilization of CDs in chiral CE are discussed specifically in the
      view of recently published data. Advantages of CDs and basic principles of chiral
      CE are remained. The topic of the determination of binding constants is touched.
      Particular attention is paid to the effort aiming at better understanding of the
      molecular level of the enantiorecognition between CDs and the analyte in the
      solution. Powerful approaches extensively utilized in this field are NMR,
      molecular modeling, and computer simulations. Then, a summary of applications of
      CDs in the CE enantioseparations is given, covering years 2008-2013. Finally, the
      general trend of modified CDs use in separation science is statistically
      evaluated. 

PMID- 24853584
TI  - Safety dominates the debate on electronic cigarettes.

PMID- 24853586
TI  - Pattern recognition in ARDS: a crucial first step toward personalised treatment.

PMID- 24853587
TI  - Interruption of infection transmission in the onchocerciasis focus of Ecuador
      leading to the cessation of ivermectin distribution.
AB  - INTRODUCTION: A clinically significant endemic focus of onchocerciasis existing
      in Esmeraldas Province, coastal Ecuador has been under an ivermectin mass drug
      administration program since 1991. The main transmitting vector in this area is
      the voracious blackfly, Simulium exiguum. This paper describes the assessments
      made that support the decision to cease mass treatment. METHODOLOGY AND PRINCIPLE
      FINDINGS: Thirty-five rounds of ivermectin treatment occurred between 1991-2009
      with 29 of these carrying >85% coverage. Following the guidelines set by WHO for
      ceasing ivermectin distribution the impact on parasite transmission was measured
      in the two vector species by an O-150 PCR technique standard for assessing for
      the presence of Onchocerca volvulus. Up to seven collection sites in three major
      river systems were tested on four occasions between 1995 and 2008. The
      infectivity rates of 65.0 (CI 39-101) and 72.7 (CI 42-116) in 1995 dropped to
      zero at all seven collection sites by 2008. Assessment for the presence of
      antibodies against O. volvulus was made in 2001, 2006, 2007 and 2008 using
      standard ELISA assays for detecting anti-Ov16 antibodies. None of total of 1810
      children aged 1-15 years (between 82 and 98% of children present in the surveyed
      villages) tested in the above years were found to be carrying antibodies to this
      antigen. These findings were the basis for the cessation of mass drug treatment
      with ivermectin in 2009. SIGNIFICANCE: This fulfillment of the criteria for
      cessation of mass distribution of ivermectin in the only known endemic zone of
      onchocerciasis in Ecuador moves the country into the surveillance phase of
      official verification for national elimination of transmission of infection.
      These findings indicate that ivermectin given twice a year with greater than 85%
      of the community can move a program to the final stages of verification of
      transmission interruption.

PMID- 24853588
TI  - Decreased c-rel activation contributes to aberrant interleukin-2 expression in
      CD4(+)T cells of aged rats.
AB  - Studies indicated significantly decreased expression of interleukin-2 (IL-2) with
      age. This decrease could be a major contributory factor to the increased
      frequency of morbidity and mortality among the elderly. C-rel is a key
      coregulator of IL-2 expression. However, it is unknown whether aging inhibits
      normal c-rel activation, thereby decreasing production of IL-2. We analyzed the
      dynamics of IL-2 expression in CD4(+)T cells from different aged rats (young
      group: around 6 months (n=6), aged group: around 24 months (n=6)). The expression
      of the CD3 receptor and CD28 receptor in the CD4(+)T cells was assessed by flow
      cytometry. Translocation of c-rel and its protein level in the cytoplasm and
      nucleus at different time points were detected by confocal microscopy and Western
      blotting. Chromatin immunoprecipitation (ChIP) was used to analyze the status of
      c-rel binding to the IL-2 promoter region in the different aged rats. Our results
      showed the CD4(+)T cells from young rats and aged rats showed different
      expression kinetics of IL-2 after stimulation. The expression level of IL-2 was
      higher in young rats compared with aged rats at 24h and 48h. Data showed lower
      CD3 receptor expression on CD4(+)T cells from aged rats compared with young rats.
      Although the CD28 receptors declined on the aged CD4(+)T cells, the difference
      was not significant. After stimulation for 0.5h, more c-rel was translocated into
      nucleus markedly compared with that in the aged group. ChIP showed that in aged
      CD4(+)T cells, c-rel DNA binding was inhabited compared with that in young cells.
      Therefore, reduced IL-2 production in activated CD4(+)T cells from aged rats is
      associated with concomitant impairments in the activation of c-rel. 

PMID- 24853590
TI  - Uveal MALT lymphoma with extensive AL-type amyloid production mimicking uveal
      melanoma.

PMID- 24853585
TI  - Subphenotypes in acute respiratory distress syndrome: latent class analysis of
      data from two randomised controlled trials.
AB  - BACKGROUND: Subphenotypes have been identified within heterogeneous diseases such
      as asthma and breast cancer, with important therapeutic implications. We assessed
      whether subphenotypes exist within acute respiratory distress syndrome (ARDS),
      another heterogeneous disorder. METHODS: We used data from two ARDS randomised
      controlled trials (ARMA trial and ALVEOLI trial), sponsored by the National
      Heart, Lung, and Blood Institute. We applied latent class modelling to identify
      subphenotypes using clinical and biological data. We modelled data from both
      studies independently. We then tested the association of subphenotypes with
      clinical outcomes in both cohorts and with the response to positive end
      expiratory pressure (PEEP) in the ALVEOLI cohort. FINDINGS: We analysed data for
      1022 patients: 473 in the ARMA cohort and 549 in the ALVEOLI cohort. Independent
      latent class models indicated that a two-class (ie, two subphenotype) model was
      the best fit for both cohorts. In both cohorts, we identified a hyperinflammatory
      subphenotype (phenotype 2) that was characterised by higher plasma concentrations
      of inflammatory biomarkers, a higher prevalence of vasopressor use, lower serum
      bicarbonate concentrations, and a higher prevalence of sepsis than phenotype 1.
      Participants in phenotype 2 had higher mortality and fewer ventilator-free days
      and organ failure-free days in both cohorts than did those in phenotype 1
      (p<0.007 for all). In the ALVEOLI cohort, the effects of ventilation strategy
      (high PEEP vs low PEEP) on mortality, ventilator-free days and organ failure-free
      days differed by phenotype (p=0.049 for mortality, p=0.018 for ventilator-free
      days, p=0.003 for organ-failure-free days). INTERPRETATION: We have identified
      two subphenotypes within ARDS, one of which is categorised by more severe
      inflammation, shock, and metabolic acidosis and by worse clinical outcomes.
      Response to treatment in a randomised trial of PEEP strategies differed on the
      basis of subphenotype. Identification of ARDS subphenotypes might be useful in
      selecting patients for future clinical trials. FUNDING: National Institutes of
      Health.

PMID- 24853589
TI  - In silico predicted mycobacterial epitope elicits in vitro T-cell responses.
AB  - Epitope-based vaccines permit the selection of only a specific subset of epitopes
      to induce the necessary immune response, thus providing a rational alternative to
      conventional design approaches. Using a range of immunoinformatics tools, we
      identified a novel, contiguous 28 amino acid multi-epitope cluster within the
      highly conserved secretory protein Ag85B of Mycobacterium tuberculosis, the
      causative agent of TB. This cluster, named Ep85B, is composed of epitopes which
      bind to three HLA Class I and 15 Class II molecules, and harbors the potential to
      generate 99% population coverage in TB-endemic regions. We experimentally
      evaluated the capacity of Ep85B to elicit T-cell immune responses using whole
      blood cells and, as predicted, observed significant increases in populations of
      both CD4+ and memory CD4+ CD45RO+ T-cells. Our results demonstrate the practical
      utility of an epitope-based design methodology - a strategy that, following
      further evaluation, may serve as an additional tool for the development of novel
      vaccine candidates against TB and other diseases. 

PMID- 24853591
TI  - A comparative study on the impact of intra-articular injections of hyaluronic
      acid, tenoxicam and betametazon on the relief of temporomandibular joint disorder
      complaints.
AB  - OBJECTIVE: The aim of this study was to compare the efficacy of intra-articular
      injections of three different agents with well known anti-inflammatory
      properties. MATERIALS AND METHOD: Between April 2010 and January 2013 a total of
      100 patients who were diagnosed as temporomandibular joint disorder in the
      Department of Otolaryngology at Bozok University School of Medicine were
      prospectively studied. Patients with symptoms of jaw pain, limited or painful jaw
      movement, clicking or grating within the joint, were evaluated with
      temporomandibular CT to investigate the presence of cartilage or capsule
      degeneration. In the study group there were 55 female and 45 male patients who
      were non-responders to conventional anti-inflammatory treatment for TMJ
      complaints. The patients were randomly divided into four groups consisting of a
      control group and three different groups who underwent intra-articular injection
      of one given anti-inflammatory agent for each group. We injected saline solution
      to intra-articular space in the control group. Of three anti-inflammatory agents
      including hyaluronic acid (HA, Hyalgan intra-articular injection, Sodium
      hyaluronate 10 mg/ml, 2 ml injection syringe, Bilim Pharmaceutical Company,
      Istanbul, Turkey); betamethasone (CS, Diprospan flacon, 7.0 mg betamethasone/1
      ml, Schering-Plough Pharmaceutical Company, Istanbul, Turkey) and; tenoxicam (TX,
      Tilcotil flacon, 20 mg tenoxicam/ml, Roche Pharmaceutical Company, Istanbul,
      Turkey) were administered intra-articularly under, ultrasonographic guidance.
      Following the completion of injections the, changes in subjective symptoms were
      compared with visual analogue scales, (VAS) scores at 1st and 6th weeks' follow
      up visits between four groups. RESULTS: The HA group did significantly better
      pain relief scores compared to the, other groups at 1st and 6th weeks (p < 0.05).
      TX and CS groups' pain scores were better than control group values (p < 0.05,
      for both agents). The pain relief effect of TX was noted to decrease
      significantly between the 1st and 6th week (p < 0.05) (Fig. 1). We did not
      observe the same pattern in HA, CS and control (saline) groups between 1st and
      6th week (p > 0.05). CONCLUSION: We found that HA produced better pain relief
      scores when compared to the other anti-inflammatory agents studied. The main
      disadvantage of HA is its relatively higher cost. Additionally it does not have a
      reimbursement status by state or private health insurance systems in Turkey.
      Despite the lower VAS scores, intra-articular TX and CS may be assessed as more
      economic alternatives to intra-articular HA injections.

PMID- 24853592
TI  - The Blackfriars Consensus on brain health and dementia.

PMID- 24853594
TI  - Survival convergence: bringing maternal and newborn health together for 2015 and
      beyond.

PMID- 24853593
TI  - Every Newborn: progress, priorities, and potential beyond survival.
AB  - In this Series paper, we review trends since the 2005 Lancet Series on Neonatal
      Survival to inform acceleration of progress for newborn health post-2015. On the
      basis of multicountry analyses and multi-stakeholder consultations, we propose
      national targets for 2035 of no more than 10 stillbirths per 1000 total births,
      and no more than 10 neonatal deaths per 1000 livebirths, compatible with the
      under-5 mortality targets of no more than 20 per 1000 livebirths. We also give
      targets for 2030. Reduction of neonatal mortality has been slower than that for
      maternal and child (1-59 months) mortality, slowest in the highest burden
      countries, especially in Africa, and reduction is even slower for stillbirth
      rates. Birth is the time of highest risk, when more than 40% of maternal deaths
      (total about 290,000) and stillbirths or neonatal deaths (5.5 million) occur
      every year. These deaths happen rapidly, needing a rapid response by health-care
      workers. The 2.9 million annual neonatal deaths worldwide are attributable to
      three main causes: infections (0.6 million), intrapartum conditions (0.7
      million), and preterm birth complications (1.0 million). Boys have a higher
      biological risk of neonatal death, but girls often have a higher social risk.
      Small size at birth--due to preterm birth or small-for-gestational-age (SGA), or
      both--is the biggest risk factor for more than 80% of neonatal deaths and
      increases risk of post-neonatal mortality, growth failure, and adult-onset non
      communicable diseases. South Asia has the highest SGA rates and sub-Saharan
      Africa has the highest preterm birth rates. Babies who are term SGA low
      birthweight (10.4 million in these regions) are at risk of stunting and adult
      onset metabolic conditions. 15 million preterm births, especially of those
      younger than 32 weeks' gestation, are at the highest risk of neonatal death, with
      ongoing post-neonatal mortality risk, and important risk of long-term
      neurodevelopmental impairment, stunting, and non-communicable conditions. 4
      million neonates annually have other life-threatening or disabling conditions
      including intrapartum-related brain injury, severe bacterial infections, or
      pathological jaundice. Half of the world's newborn babies do not get a birth
      certificate, and most neonatal deaths and almost all stillbirths have no death
      certificate. To count deaths is crucial to change them. Failure to improve birth
      outcomes by 2035 will result in an estimated 116 million deaths, 99 million
      survivors with disability or lost development potential, and millions of adults
      at increased risk of non-communicable diseases after low birthweight. In the post
      2015 era, improvements in child survival, development, and human capital depend
      on ensuring a healthy start for every newborn baby--the citizens and workforce of
      the future.

PMID- 24853595
TI  - Integration and innovation to advance newborn survival.

PMID- 24853597
TI  - Newborn health: a revolution in waiting.

PMID- 24853598
TI  - The world we want for every newborn child.

PMID- 24853596
TI  - Newborn health research priorities beyond 2015.

PMID- 24853599
TI  - From evidence to action to deliver a healthy start for the next generation.
AB  - Remarkable progress has been made towards halving of maternal deaths and deaths
      of children aged 1-59 months, although the task is incomplete. Newborn deaths and
      stillbirths were largely invisible in the Millennium Development Goals, and have
      continued to fall between maternal and child health efforts, with much slower
      reduction. This Series and the Every Newborn Action Plan outline mortality goals
      for newborn babies (ten or fewer per 1000 livebirths) and stillbirths (ten or
      fewer per 1000 total births) by 2035, aligning with A Promise Renewed target for
      children and the vision of Every Woman Every Child. To focus political attention
      and improve performance, goals for newborn babies and stillbirths must be
      recognised in the post-2015 framework, with corresponding accountability
      mechanisms. The four previous papers in this Every Newborn Series show the
      potential for a triple return on investment around the time of birth: averting
      maternal and newborn deaths and preventing stillbirths. Beyond survival, being
      counted and optimum nutrition and development is a human right for all children,
      including those with disabilities. Improved human capital brings economic
      productivity. Efforts to reach every woman and every newborn baby, close gaps in
      coverage, and improve equity and quality for antenatal, intrapartum, and
      postnatal care, especially in the poorest countries and for underserved
      populations, need urgent attention. We have prioritised what needs to be done
      differently on the basis of learning from the past decade about what has worked,
      and what has not. Needed now are four most important shifts: (1) intensification
      of political attention and leadership; (2) promotion of parent voice, supporting
      women, families, and communities to speak up for their newborn babies and to
      challenge social norms that accept these deaths as inevitable; (3) investment for
      effect on mortality outcome as well as harmonisation of funding; (4)
      implementation at scale, with particular attention to increasing of health worker
      numbers and skills with attention to high-quality childbirth care for newborn
      babies as well as mothers and children; and (5) evaluation, tracking coverage of
      priority interventions and packages of care with clear accountability to
      accelerate progress and reach the poorest groups. The Every Newborn Action Plan
      provides an evidence-based roadmap towards care for every woman, and a healthy
      start for every newborn baby, with a right to be counted, survive, and thrive
      wherever they are born. 

PMID- 24853600
TI  - Every Newborn: health-systems bottlenecks and strategies to accelerate scale-up
      in countries.
AB  - Universal coverage of essential interventions would reduce neonatal deaths by an
      estimated 71%, benefit women and children after the first month, and reduce
      stillbirths. However, the packages with the greatest effect (care around birth,
      care of small and ill newborn babies), have low and inequitable coverage and are
      the most sensitive markers of health system function. In eight of the 13
      countries with the most neonatal deaths (55% worldwide), we undertook a
      systematic assessment of bottlenecks to essential maternal and newborn health
      care, involving more than 600 experts. Of 2465 bottlenecks identified, common
      constraints were found in all high-burden countries, notably regarding the health
      workforce, financing, and service delivery. However, bottlenecks for specific
      interventions might differ across similar health systems. For example, the
      implementation of kangaroo mother care was noted as challenging in the four Asian
      country workshops, but was regarded as a feasible aspect of preterm care by
      respondents in the four African countries. If all high-burden countries achieved
      the neonatal mortality rates of their region's fastest progressing countries,
      then the mortality goal of ten or fewer per 1000 livebirths by 2035 recommended
      in this Series and the Every Newborn Action Plan would be exceeded. We therefore
      examined fast progressing countries to identify strategies to reduce neonatal
      mortality. We identified several key factors: (1) workforce planning to increase
      numbers and upgrade specific skills for care at birth and of small and ill
      newborn babies, task sharing, incentives for rural health workers; (2) financial
      protection measures, such as expansion of health insurance, conditional cash
      transfers, and performance-based financing; and (3) dynamic leadership including
      innovation and community empowerment. Adapting from the 2005 Lancet Series on
      neonatal survival and drawing on this Every Newborn Series, we propose a country
      led, data-driven process to sharpen national health plans, seize opportunities to
      address the quality gap for care at birth and care of small and ill newborn
      babies, and systematically scale up care to reach every mother and newborn baby,
      particularly the poorest. 

PMID- 24853601
TI  - Global surgery: defining an emerging global health field.

PMID- 24853602
TI  - Every Newborn: the professional organisations' perspective.

PMID- 24853603
TI  - Who has been caring for the baby?
AB  - Nearly a decade ago, The Lancet published the Neonatal Survival Series, with an
      ambitious call for integration of newborn care across the continuum of
      reproductive, maternal, newborn, and child health and nutrition (RMNCH). In this
      first of five papers in the Every Newborn Series, we consider what has changed
      during this decade, assessing progress on the basis of a systematic policy
      heuristic including agenda-setting, policy formulation and adoption, leadership
      and partnership, implementation, and evaluation of effect. Substantial progress
      has been made in agenda setting and policy formulation for newborn health, as
      witnessed by the shift from maternal and child health to maternal, newborn, and
      child health as a standard. However, investment and large-scale implementation
      have been disappointingly small, especially in view of the size of the burden and
      potential for rapid change and synergies throughout the RMNCH continuum.
      Moreover, stillbirths remain invisible on the global health agenda. Hence that
      progress in improvement of newborn survival and reduction of stillbirths lags
      behind that of maternal mortality and deaths for children aged 1-59 months is not
      surprising. Faster progress is possible, but with several requirements: clear
      communication of the interventions with the greatest effect and how to overcome
      bottlenecks for scale-up; national leadership, and technical capacity to
      integrate and implement these interventions; global coordination of partners,
      especially within countries, in provision of technical assistance and increased
      funding; increased domestic investment in newborn health, and access to specific
      commodities and equipment where needed; better data to monitor progress, with
      local data used for programme improvement; and accountability for results at all
      levels, including demand from communities and mortality targets in the post-2015
      framework. Who will step up during the next decade to ensure decision making in
      countries leads to implementation of stillbirth and newborn health interventions
      within RMNCH programmes? 

PMID- 24853605
TI  - The Card Placing Test: a new test for evaluating the function of the
      retrosplenial and posterior cingulate cortices.
AB  - BACKGROUND/AIM: We developed a test named the Card Placing Test (CPT), which is
      potentially useful for evaluating a function of the retrosplenial and posterior
      cingulate cortices (RSC/PCC). Part A of the test assesses the ability of a
      subject to retain information on spatial locations of cards placed on the floor
      around the subject. Part B examines the subject's ability to integrate
      information on the spatial locations of similarly arranged cards and information
      on changes in body direction. The aim of this study is to identify brain regions
      involved in the CPT performance. SUBJECTS AND METHODS: Twenty-five subjects were
      recruited from our memory clinic. We analyzed the correlation between the CPT
      scores and resting state regional cerebral blood flow (rCBF) determined by single
      photon emission tomography. RESULTS: The scores for part A correlated with rCBF
      in the right inferior parietal lobule. The scores for part B were associated with
      rCBF in the RSC/PCC. CONCLUSIONS: The right inferior parietal lobule seems to
      play a pivotal role in performing part A of the CPT, whereas the RSC/PCC appears
      to be involved in accomplishing part B of the CPT.

PMID- 24853606
TI  - A nanotree-like CdS/ZnO nanocomposite with spatially branched hierarchical
      structure for photocatalytic fine-chemical synthesis.
AB  - Branched hierarchical CdS/ZnO nanocomposites have been synthesized for
      application toward photocatalytic fine-chemical synthesis. Growing ZnO nanorods
      on the surface of CdS nanowires boosts the light harvesting efficiency and charge
      separation as well as fast charge transport and collection. A Z-scheme mechanism
      under artificial solar light is also proposed. 

PMID- 24853604
TI  - Can available interventions end preventable deaths in mothers, newborn babies,
      and stillbirths, and at what cost?
AB  - Progress in newborn survival has been slow, and even more so for reductions in
      stillbirths. To meet Every Newborn targets of ten or fewer neonatal deaths and
      ten or fewer stillbirths per 1000 births in every country by 2035 will
      necessitate accelerated scale-up of the most effective care targeting major
      causes of newborn deaths. We have systematically reviewed interventions across
      the continuum of care and various delivery platforms, and then modelled the
      effect and cost of scale-up in the 75 high-burden Countdown countries. Closure of
      the quality gap through the provision of effective care for all women and newborn
      babies delivering in facilities could prevent an estimated 113,000 maternal
      deaths, 531,000 stillbirths, and 1.325 million neonatal deaths annually by 2020
      at an estimated running cost of US$4.5 billion per year (US$0.9 per person).
      Increased coverage and quality of preconception, antenatal, intrapartum, and
      postnatal interventions by 2025 could avert 71% of neonatal deaths (1.9 million
      [range 1.6-2.1 million]), 33% of stillbirths (0.82 million [0.60-0.93 million]),
      and 54% of maternal deaths (0.16 million [0.14-0.17 million]) per year. These
      reductions can be achieved at an annual incremental running cost of US$5.65
      billion (US$1.15 per person), which amounts to US$1928 for each life saved,
      including stillbirths, neonatal, and maternal deaths. Most (82%) of this effect
      is attributable to facility-based care which, although more expensive than
      community-based strategies, improves the likelihood of survival. Most of the
      running costs are also for facility-based care (US$3.66 billion or 64%), even
      without the cost of new hospitals and country-specific capital inputs being
      factored in. The maximum effect on neonatal deaths is through interventions
      delivered during labour and birth, including for obstetric complications (41%),
      followed by care of small and ill newborn babies (30%). To meet the unmet need
      for family planning with modern contraceptives would be synergistic, and would
      contribute to around a halving of births and therefore deaths. Our analysis also
      indicates that available interventions can reduce the three most common cause of
      neonatal mortality--preterm, intrapartum, and infection-related deaths--by 58%,
      79%, and 84%, respectively.

PMID- 24853607
TI  - Malaysian growth centiles for children under six years old.
AB  - BACKGROUND: Growth references are useful for the screening, assessment and
      monitoring of individual children as well as for evaluating various growth
      promoting interventions that could possibly affect a child in early life. AIM: To
      determine the growth centiles of Malaysian children and to establish contemporary
      cross-sectional growth reference charts for height and weight from birth to 6
      years of age based on a representative sample of children from Malaysia. METHODS:
      Gender- and age-specific centile curves for height and weight were derived using
      the Cole's LMS method. Data for this study were retrieved from Malaysian
      government health clinics using a two-stage stratified random sampling technique.
      Assessment of nutritional status was done with the SD scores (Z-scores) of WHO
      2006 standards. RESULTS: Boys were found to be taller and heavier than girls in
      this study. The median length of Malaysian children was higher than the WHO 2006
      standards and CDC 2000 reference. The overall prevalence of stunting and
      underweight were 8.3% and 9.3%, respectively. CONCLUSIONS: This study presents
      the first large-scale initiative for local reference charts. The growth reference
      would enable the growth assessment of a Malaysian child compared to the average
      growth of children in the country. It is suggested that the use of WHO 2006 Child
      Growth Standards should be complemented with local reference charts for a more
      wholesome growth assessment.

PMID- 24853608
TI  - Electrogenerated chemiluminescence of donor-acceptor molecules with thermally
      activated delayed fluorescence.
AB  - The electrochemistry and electrogenerated chemiluminescence (ECL) of four kinds
      of electron donor-acceptor molecules exhibiting thermally activated delayed
      fluorescence (TADF) is presented. TADF molecules can harvest light energy from
      the lowest triplet state by spin up-conversion to the lowest singlet state
      because of small energy gap between these states. Intense green to red ECL is
      emitted from the TADF molecules by applying a square-wave voltage. Remarkably, it
      is shown that the efficiency of ECL from one of the TADF molecule could reach
      about 50%, which is comparable to its photoluminescence quantum yield.

PMID- 24853609
TI  - A new era of targeting the ancient gatekeepers of the immune system: toll-like
      agonists in the treatment of allergic rhinitis and asthma.
AB  - Toll-like receptors (TLR) belong to a large family of pattern recognition
      receptors known as the ancient 'gatekeepers' of the immune system. TLRs are
      located at the first line of defense against invading pathogens as well as
      aeroallergens, making them interesting targets to modulate the natural history of
      respiratory allergy. Agonists of TLRs have been widely employed in therapeutic or
      prophylactic preparations useful for asthma/allergic rhinitis (AR) patients.
      MPL(r) (a TLR4 agonist) and the CpG oligodeoxynucleotide of 1018 ISS, a TLR9
      agonist, show strong immunogenicity effects that make them appropriate adjuvants
      for allergy vaccines. Targeting the TLRs can enhance the efficacy of specific
      allergen immunotherapy, currently the only available 'curative' treatment for
      respiratory allergies. In addition, intranasal administration of AZD8848 (a TLR7
      agonist) and VTX-1463 (a TLR8 agonist) as stand-alone therapeutics have revealed
      efficacy in the relief of the symptoms of AR patients. No anaphylaxis has been so
      far reported with such compounds targeting TLRs, with the most common adverse
      effects being transient and local irritation (e.g. redness, swelling and
      pruritus). Many other compounds that target TLRs have been found to suppress
      airway inflammation, eosinophilia and airway hyper-responsiveness in various
      animal models of allergic inflammation. Indeed, in the future a wide variability
      of TLR agonists and even antagonists that exhibit anti-asthma/AR effects are
      likely to emerge.

PMID- 24853610
TI  - Tobacco smoke exposure in pulmonary arterial and thromboembolic pulmonary
      hypertension.
AB  - BACKGROUND: Animal studies and data from a single-center study suggest that
      tobacco smoke exposure may be a risk factor for precapillary pulmonary
      hypertension (PH). OBJECTIVE: We aimed to survey tobacco smoke exposure in a
      large PH collective and to compare it with epidemiological data from healthy
      subjects. METHODS: This is an international, multicenter, case-control study
      including patients with pulmonary arterial and chronic thromboembolic PH. All
      patients were asked specific questions about tobacco smoke exposure. Healthy
      controls were retrieved from the Swiss Health Survey (n = 18,747). RESULTS:
      Overall (n = 472), 49% of PH patients were smokers and there was a clear sex
      difference (women 37%, men 71%). Significantly more PH men were smokers compared
      with healthy controls, whereas less PH women were ever active smokers. However,
      50% of the non-smoking PH women were exposed to secondhand smoke, leading to a
      significantly higher number of tobacco smoke-exposed individuals compared to
      healthy controls. PH smokers were significantly younger compared to those not
      exposed. CONCLUSION: Active and environmental tobacco smoke exposure is common in
      PH. The higher prevalence of male PH smokers, the higher exposure to
      environmental tobacco smoke in PH women compared to healthy controls and the
      lower age at PH diagnosis in smokers may indicate a pathogenic role of tobacco
      smoke exposure in PH.

PMID- 24853611
TI  - Ischemic versus pharmacologic hepatic preconditioning.
AB  - BACKGROUND: Hepatic ischemia-reperfusion injury has a significant impact on liver
      resection and transplantation. Many strategies have been developed to reduce the
      effects of ischemia-reperfusion injury, including pharmacologic and ischemic
      preconditioning; however, studies comparing these two methods are lacking.
      MATERIAL AND METHODS: An experimental study was performed in a swine model.
      Eighteen swine were randomly assigned to three different groups: an ischemic
      preconditioning (IschPC) group, a pharmacologic preconditioning (PharmPC) group,
      and a control group. All animals underwent a 40-min liver ischemia, followed by
      40 min of reperfusion. The IschPC group received a short period of ischemia (10
      min) and a short period of reperfusion (15 min) before prolonged ischemia. The
      PharmPC group received inhaled sevoflurane for 30 min before prolonged ischemia.
      The control group did not receive any intervention before prolonged ischemia.
      Blood samples and liver tissue were obtained after ischemic and reperfusion
      periods. Injury was evaluated by measure of DNA damage (using COMET assay) and
      serum biochemical markers (transaminases, alkaline phosphatase, amylase,
      bilirubin, and C-reactive protein [CRP]). RESULTS: No significant difference was
      found in serum biochemical markers, except for the C-reactive protein level that
      was lower in the PharmPC group than in the control group soon after hepatic
      ischemia. Soon after prolonged ischemia, DNA damage index, both in blood samples
      and in liver tissue samples, was similar among the groups. However, an increase
      in DNA damage after reperfusion was higher in the control group than in the
      PharmPC group (P < 0.05). The increase in DNA damage in the IschPC group was half
      of that observed in the control, but this difference was not statistically
      significant. CONCLUSIONS: Our results suggest an early protective effect of
      PharmPC (lower levels of C-reactive protein soon after ischemia). The protective
      effect observed after reperfusion was higher with PharmPC than with ischemic
      preconditioning. The simultaneous use of both methods could potentiate protection
      for ischemia-reperfusion.

PMID- 24853612
TI  - Sensiprobe--a miniature thermal device incorporating Peltier technology as a
      diagnostic tool for studying human oesophageal sensitivity.
AB  - Heightened perception of gastrointestinal sensation is termed visceral
      hypersensitivity (VH) and is commonly observed in patients with gastrointestinal
      disorders. VH is thought to be a major contributory factor in oesophageal
      disease, particularly gastro-oesophageal reflux disease that does not respond to
      standard (proton pump inhibitor) treatment, and in functional heartburn. Clinical
      tools that can help phenotype according to the mechanism of chronic pain and thus
      allow targeted drug treatment (e.g. with pain modulator therapy) would be very
      desirable. A technique that produces repeatable and controllable thermal stimuli
      within the oesophagus could meet this need. The aims of this study were to
      develop a method for linear control of the heat stimulation in the oesophagus, to
      assess the reproducibility of this method, and obtain normal thermal sensitivity
      values in the distal and proximal oesophagus. The 7 mm diameter Peltier-based
      thermal device was investigated on 27 healthy subjects using a heating ramp of
      0.2  degrees C s(-1). The pain detection threshold (PDT) temperature was
      recorded. To assess the reproducibility of the device, each subject underwent the
      procedure twice, with a minimum of two weeks between each procedure. The mean PDT
      temperature measured in the distal oesophagus, was 53.8 +/- 2.9  degrees C and
      53.6 +/- 2.6  degrees C, for visits 1 and 2 respectively. The mean PDT
      temperature measured in the proximal oesophagus was 54.1 +/- 2.4  degrees C and
      54.0 +/- 2.8  degrees C, for visits 1 and 2 respectively. The reproducibility of
      the PDT temperature in the distal and proximal oesophagus, was good (intra-class
      correlation >0.6). Future studies should be aimed to determine whether
      oesophageal thermal sensitivity can act as a biomarker of transient receptor
      potential vallanoid 1 upregulation. 

PMID- 24853613
TI  - Lagerstroemia speciosa L. attenuates apoptosis in isoproterenol-induced
      cardiotoxic mice by inhibiting oxidative stress: possible role of Nrf2/HO-1.
AB  - Myocardial oxidative stress leading to apoptosis and remodeling is the major
      consequence of ischemic heart disease. In the present study, we investigated the
      effect of Lagerstroemia speciosa L. leave (LS) extract containing 1 % corosolic
      acid in the context of cardiovascular disorder by using isoproterenol (ISO)
      induced myocardial injury mouse model. Serum was analyzed for specific cardiac
      injury biomarkers. Cardiac tissue was examined for lipid peroxidation, protein
      carbonyl content, antioxidant (GSH, GR, GPx, GST, SOD, CAT, NQO1, and HO-1), and
      apoptosis (cleaved caspase-3, Bax, Bcl-2, p53, and DNA fragmentation) status.
      Myocardial protein expression of nuclear factor erythroid 2-related factor 2
      (Nrf2) in different experimental groups was evaluated. Pathological changes in
      heart tissue and activities of matrix metalloproteinases (MMPs) were also
      analyzed. Our results demonstrated that LS pretreatment augmented myocardial
      antioxidant status and attenuated myocardial oxidative stress. Myocardial
      apoptosis as well as MMPs activities was significantly prevented by LS
      pretreatment in ISO-induced mice. In addition, the immunoblot of Nrf2 revealed
      that LS pretreatment enhanced the nuclear protein expression of Nrf2 when
      compared to ISO control group. Thus, the overall results indicate that LS has
      cardioprotective effect and may prevent the myocardial stress by suppressing
      apoptosis through up-regulation of myocardial antioxidant levels. 

PMID- 24853614
TI  - CopA3 peptide prevents ultraviolet-induced inhibition of type-I procollagen and
      induction of matrix metalloproteinase-1 in human skin fibroblasts.
AB  - Ultraviolet (UV) exposure is well-known to induce premature aging, which is
      mediated by matrix metalloproteinase-1 (MMP-1) activity. A 9-mer peptide, CopA3
      (CopA3) was synthesized from a natural peptide, coprisin, which is isolated from
      the dung beetle Copris tripartitus. As part of our continuing search for novel
      bioactive natural products, CopA3 was investigated for its in vitro anti-skin
      photoaging activity. UV-induced inhibition of type-I procollagen and induction of
      MMP-1 were partially prevented in human skin fibroblasts by CopA3 peptide in a
      dose-dependent manner. At a concentration of 25 MUM, CopA3 nearly completely
      inhibited MMP-1 expression. These results suggest that CopA3, an insect peptide,
      is a potential candidate for the prevention and treatment of skin aging. 

PMID- 24853615
TI  - 2,5-PRODAN derivatives as highly sensitive sensors of low solvent acidity.
AB  - Two 5-acyl-2-dimethylaminonaphthalene derivatives, one with a propionyl group and
      the other with a fused cyclohexanone ring, are investigated as sensors of H-bond
      donating ability in protic solvents of low solvent acidity. Their fluorescence is
      highly quenched in protic solvents, and the quenching order of magnitude is
      linearly related to the H-bond-donating ability of the solvent as quantified by
      the solvent acidity (SA) scale. As the solvent acidity increases from 0.15 to
      0.40, the fluorescence for both is quenched by more than a factor of ten; thus,
      they are extremely sensitive sensors of the hydrogen-bond-donating ability in
      this weakly acidic range. Preferential solvation studies suggest that quenching
      occurs from a doubly H-bonded excited state. 

PMID- 24853616
TI  - Antiprotozoal activity of Achillea ptarmica (Asteraceae) and its main alkamide
      constituents.
AB  - In the course of our ongoing screening of plants of the family Asteraceae for
      antiprotozoal activity, a CH2Cl2-extract from the flowering aerial parts of
      Achillea ptarmica L. (sneezewort yarrow) was found to be active in vitro against
      Trypanosoma brucei rhodesiense (IC50 = 0.67 ug/mL) and Plasmodium falciparum
      (IC50 = 6.6 MUg/mL). Bioassay guided fractionation led to the isolation and
      identification of five alkamides from the most active fractions. Pellitorine and
      8,9-Z-dehyropellitorine are the main components of the extract. Beside these
      olefinic acid amides, four alkamides with diene-diyne structures were isolated.
      All alkamides were tested for antiprotozoal activity in vitro. Pellitorine was
      the most active compound so far within this study against P. falciparum (IC50 =
      3.3 ug/mL), while 8,9-Z-dehydropellitorine was most active against T. b.
      rhodesiense (IC50 = 2.0 ug/mL). The activity of pure pellitorine against
      Plasmodium is higher than that of the crude extract and thus explains the
      activity of the latter. None of the isolated alkamides, however, was as active
      against T. b. rhodesiense as the crude extract whose antitrypanosomal activity
      must therfore be due to a synergistic effect of the isolated compounds or to more
      active yet to be identified constituents. 

PMID- 24853617
TI  - Palladium-catalyzed direct addition of 2-aminobenzonitriles to sodium
      arylsulfinates: synthesis of o-aminobenzophenones.
AB  - The first example of the palladium-catalyzed synthesis of o-aminobenzophenones in
      moderate to excellent yields via a direct addition of sodium arylsulfinates to
      unprotected 2-aminobenzonitriles was reported. A plausible mechanism for the
      formation of o-aminobenzophenones involving desulfination and addition reactions
      was proposed. The utility of this transformation was demonstrated by its
      compatibility with a wide range of functional groups. Thus, the method represents
      a convenient and practical strategy for synthesis of o-aminobenzophenones. 

PMID- 24853618
TI  - Chlorine isotope effects from isotope ratio mass spectrometry suggest
      intramolecular C-Cl bond competition in trichloroethene (TCE) reductive
      dehalogenation.
AB  - Chlorinated ethenes are prevalent groundwater contaminants. To better constrain
      (bio)chemical reaction mechanisms of reductive dechlorination, the position
      specificity of reductive trichloroethene (TCE) dehalogenation was investigated.
      Selective biotransformation reactions (i) of tetrachloroethene (PCE) to TCE in
      cultures of Desulfitobacterium sp. strain Viet1; and (ii) of TCE to cis-1,2
      dichloroethene (cis-DCE) in cultures of Geobacter lovleyi strain SZ were
      investigated. Compound-average carbon isotope effects were -19.00/00 +/- 0.90/00
      (PCE) and -12.20/00 +/- 1.00/00 (TCE) (95% confidence intervals). Using
      instrumental advances in chlorine isotope analysis by continuous flow isotope
      ratio mass spectrometry, compound-average chorine isotope effects were measured
      for PCE (-5.00/00 +/- 0.10/00) and TCE (-3.60/00 +/- 0.20/00). In addition,
      position-specific kinetic chlorine isotope effects were determined from fits of
      reactant and product isotope ratios. In PCE biodegradation, primary chlorine
      isotope effects were substantially larger (by -16.30/00 +/- 1.40/00 (standard
      error)) than secondary. In TCE biodegradation, in contrast, the product cis-DCE
      reflected an average isotope effect of -2.40/00 +/- 0.30/00 and the product
      chloride an isotope effect of -6.50/00 +/- 2.50/00, in the original positions of
      TCE from which the products were formed (95% confidence intervals). A greater
      difference would be expected for a position-specific reaction (chloride would
      exclusively reflect a primary isotope effect). These results therefore suggest
      that both vicinal chlorine substituents of TCE were reactive (intramolecular
      competition). This finding puts new constraints on mechanistic scenarios and
      favours either nucleophilic addition by Co(I) or single electron transfer as
      reductive dehalogenation mechanisms. 

PMID- 24853619
TI  - Can extracorporeal magnetic innervation be a treatment modality for primary
      dysmenorrhea?
AB  - BACKGROUND/AIMS: To evaluate the efficacy of extracorporeal magnetic innervation
      (ExMI) as a treatment for primary dysmenorrhea compared with nonsteroidal anti
      inflammatory drugs (NSAIDs) and combined oral contraceptives (COCs). METHODS: The
      cases were randomized into three groups (NSAID = 51, ExMI = 53, COC = 54). ExMI
      was applied for a total of 10 sessions. Women in the NSAID group used an oral
      NSAID at the start of each menstruation. Women in the COC group were given
      combined pills. Of the treatment options, ExMI was applied for only a single
      period, whereas NSAID and COC use continued for 12 months. RESULTS: At the first
      menstruation, visual analog scale (VAS) scores improved significantly in all
      groups (p < 0.001). NSAIDs and COCs continued to show efficacy over the entire
      study period (p < 0.05). However, in the ExMI group, VAS values increased from
      the first menstruation until 12 months. The VAS score at the 12th month was
      significantly higher in the ExMI group than in the other groups (p < 0.05), but
      markedly lower than the pretreatment value (49.9 +/- 8.3 vs. 71.1 +/- 10.1, p <
      0.001). CONCLUSIONS: ExMI therapy might be a promising novel noninvasive option
      for primary dysmenorrhea. Efficacy began to decline after 3 months, but continued
      for 12 months.

PMID- 24853620
TI  - Pharmaceutical impurities and degradation products: uses and applications of NMR
      techniques.
AB  - Current standards and regulations demand the pharmaceutical industry not only to
      produce highly pure drug substances, but to achieve a thorough understanding of
      the impurities accompanying their manufactured drug substances and products.
      These challenges have become important goals of process chemistry and have
      steadily stimulated the search of impurities after accelerated or forced
      degradation procedures. As a result, impurity profiling is one of the most
      attractive, active and relevant fields of modern pharmaceutical analysis. This
      activity includes the identification, structural elucidation and quantitative
      determination of impurities and degradation products in bulk drugs and their
      pharmaceutical formulations. Nuclear magnetic resonance (NMR) spectroscopy has
      evolved into an irreplaceable approach for pharmaceutical quality assessment,
      currently playing a critical role in unequivocal structure identification as well
      as structural confirmation (qualitative detection), enabling the understanding of
      the underlying mechanisms of the formation of process and/or degradation
      impurities. NMR is able to provide qualitative information without the need of
      standards of the unknown compounds and multiple components can be quantified in a
      complex sample without previous separation. When coupled to separative
      techniques, the resulting hyphenated methodologies enhance the analytical power
      of this spectroscopy to previously unknown levels. As a result, and by enabling
      the implementation of rational decisions regarding the identity and level of
      impurities, NMR contributes to the goal of making better and safer medicines.
      Herein are discussed the applications of NMR spectroscopy and its hyphenated
      derivate techniques to the study of a wide range pharmaceutical impurities.
      Details on the advantages and disadvantages of the methodology and well as
      specific challenges with regards to the different analytical problems are also
      presented. 

PMID- 24853621
TI  - Quantitative evaluation of the in vitro effect and interactions of active
      fractions in Yaotongning-based formulae on prostaglandin E2 production.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine (TCM) formula of
      Yaotongning Capsules (YTNC) is a common remedy to treat rheumatism (RA) in China
      and possesses diverse biological activities including anti-inflammation. However
      the effects of component material medicines (CMMs) in YTNC and different
      combinations of the CMMs on the efficacy of YTNC and the interactions of these
      CMMs have been being unclear due to ten CMMs and too many compounds involved in
      YTNC. Moreover, many TCM formulae are available for treating RA according to TCM
      theory. It is unknown if the YTNC prescription is better than other TCM formulae
      for treating RA or better efficacy could be obtained when some CMMs in YTNC are
      replaced by other herbs. Quantitatively investigate the in vitro effect of active
      fractions from the CMMs of YTNC and other eight herbs commonly used in the TCM
      formulae for RA treatment on anti-inflammatory activity of different combinations
      of the active fractions, the interactions of the active fractions to evaluate the
      reasonability, advantage (or disadvantage) of the YTNC prescription and to see if
      the prescription could be improved from the point of anti-inflammation. MATERIALS
      AND METHODS: Twenty-six active fractions, which were categorized as alkaloids,
      flavonoids, saponins, volatile oils/aqueous extracts and polysaccharides were
      prepared to design TCM samples by combining some of the active fractions, based
      on the YTNC formulating principle, combination chemistry concept and the
      importance of the active fractions in YTNC. The anti-inflammatory activities of
      the samples were evaluated by their half-maximal inhibitory concentration (IC50)
      values that inhibiting the production of prostaglandin E2 (PGE2) in ANA-1 murine
      macrophages (ANA-1 cells). The cells plated in 96-well plates were classified
      into blank group and test sample group. Each group was stimulated with
      lipopolysaccharides (LPS, 1 mg/mL) for 2h. ANA-1 cells were pretreated with
      different concentrations of test samples prior to the addition of arachidonic
      acid (10 MUmol/L). The supernatants were collected and measured using PGE2 ELISA
      Kit, and the cytotoxicity was assayed by cell counting Kit-8 (CCK8)-based test.
      The interactions of the active fractions in YTNC were evaluated by comparing the
      experimental IC50 values of the samples derived from YTNC to their corresponding
      additive IC50 values. The effect of each active fraction on cellular anti
      inflammation-PGE2 secretion inhibition activity, and the reasonability,
      advantages (or disadvantages) of YTNC were evaluated based on the comparison of
      IC50 values of the samples. RESULTS: The disassembled formulae consisted of some
      active fractions of YTNC and the whole prescription of YTNC consisted of the all
      active fractions from YTNC all demonstrate cellular anti-inflammatory activity,
      and there were no significant differences between these formulae. The vehicle of
      YTNC Chinese rice wine exhibits the ability to enhance the cellular anti
      inflammation of YTNC. Synergistic effect exerts in the combination of alkaloids,
      flavonoids and saponins of YTNC, antagonistic or additive effects occur in the
      other combinations of active fractions from YTNC. The anti-inflammatory
      activities of some TCM samples which include some active fractions from the eight
      selected herbs are significantly higher than the samples derived from YTNC. The
      flavonoids of Carthamus tinctorius, the volatile oils of Cinnamomum cassia and
      Angelica pubescens perform better in cellular anti-inflammation than the
      flavonoids and volatile oils in YTNC. CONCLUSIONS: The prescription of YTNC is
      reasonable in the view of anti-inflammation. The saponins and polysaccharides
      from the CMMs of YTNC have better anti-inflammatory activities than the saponins
      and polysaccharides from the other eight herbs. Reducing the varieties of YTNC
      CMMs and replacing the flavonoids and volatile oils of YTNC with the flavonoids
      of Carthamus tinctorius and the volatile oils of Cinnamomum cassia (or Angelica
      pubescens) would improve the safety and anti-inflammatory activity of YTNC.
      Synthetically evaluating various pharmacological activities of TCM formulae
      designed in the present work may lead to develop more effective and safer TCM
      using YTNC as prototypes.

PMID- 24853622
TI  - Human placenta mesenchymal stem cells expressing exogenous kringle1-5 protein by
      fiber-modified adenovirus suppress angiogenesis.
AB  - Anti-angiogenesis gene therapy is considered a promising treatment for excessive
      vascularization. Mesenchymal stem cell (MSC)-based gene therapy may enhance the
      effect of anti-angiogenesis by maintaining a long therapeutic period in vivo.
      However, transduction efficiencies and transgene expression in MSC-based gene
      therapy should be improved. Here we report human placenta-derived MSC (HPMSC)
      based gene therapy using a fiber-modified adenoviral vector carrying the kringle1
      5 gene to maintain long-term survival and effectively suppress angiogenesis both
      in vitro and in vivo. HPMSCs infected by the adenoviral vector were transduced at
      high efficiency with a low multiplicity of infection, and the infected HPMSCs
      expressed exogenous kringle1-5 protein in vitro and in vivo. Infected HPMSCs were
      detected at 2 weeks in vivo by fluorescence imaging and immunohistochemistry of
      reporter gene expression. Importantly, the microvessel growth of aortic rings in
      vitro was inhibited by administration of infected HPMSCs expressing kringle1-5
      protein (K1-5-HPMSCs) at day 6. In Matrigel plugs combined with K1-5-HPMSCs,
      microvessel density was decreased as detected by immunohistochemistry and blood
      flow was decreased as detected by the power Doppler contrast enhanced at day 14.
      The fiber-modified adenovirus is an effective gene vector for HPMSC-based gene
      therapy, which may be a promising strategy for cancer anti-angiogenesis. 

PMID- 24853623
TI  - Co-abrogation of Chk1 and Chk2 by potent oncolytic adenovirus potentiates the
      antitumor efficacy of cisplatin or irradiation.
AB  - Mammalian checkpoint kinases 1 and 2 (Chk1 and Chk2) are essential kinases that
      are involved in cell cycle checkpoint control, and the abrogation of either has
      been proposed as one way to sensitize cancer cells to DNA-damaging agents.
      However, it remains unclear which kinase is the most therapeutically relevant
      target, and whether multiple kinases might need to be targeted to achieve the
      best efficacy because of their overlapping substrate spectra and redundant
      functions. To clarify this issue, we established asynchronous cell cycle arrest
      models to investigate the therapeutic outcomes of silencing Chk1 and Chk2 in the
      presence of irradiation or cisplatin. Our results showed that Chk1- and Chk2
      targeting small interference RNAs (siRNAs) demonstrated synergistic effects when
      both siRNAs were used simultaneously. Interestingly, Chk1 and Chk2 co-expression
      occurred in ~90% of neoplastic tissues examined and showed no difference in
      neoplastic versus non-neoplastic tissues. Therefore, the selective targeting of
      Chk1 and Chk2 by oncolytic adenovirus mutants was chosen to treat resistant tumor
      xenograft mice, and the maximum antitumoral efficacy was achieved with the
      combined co-abrogation of Chk1 and Chk2 in the presence of low-dose cisplatin.
      This work deepens our understanding of novel strategies that target checkpoint
      pathways and contributes to the development of novel, potent and safe checkpoint
      abrogators. 

PMID- 24853625
TI  - Mentha pulegium extract as a natural product for the inhibition of corrosion.
      Part I: electrochemical studies.
AB  - The inhibitory effect of Mentha pulegium extract (MPE) on steel corrosion in 1 M
      HCl solution was investigated using potentiodynamic polarisation and
      electrochemical impedance spectroscopy. The inhibition efficiency of MPE was
      found to increase with the concentration and reached 88% at 33% (v/v).
      Polarisation measurements show that the natural extract acted as a mixed
      inhibitor. The remarkable inhibition efficiency of MPE was discussed in terms of
      blocking of electrode surface by adsorption of inhibitor molecules through active
      centres. The adsorption of MPE was found to accord with the Temkin isotherm.

PMID- 24853624
TI  - The PPARgamma agonist Troglitazone induces autophagy, apoptosis and necroptosis
      in bladder cancer cells.
AB  - Bladder cancer is a major public health problem worldwide, with relatively high
      morbidity. However, there are few studies on drug development for bladder cancer.
      Troglitazone (TZ) is a synthetic ligand of peroxisome proliferator-activated
      receptor-gamma, and it can induce apoptosis and autophagy in a variety of cancer
      cells. Several studies have indicated that TZ affects both cell growth and
      differentiation progress and has an inhibitory effect on urinary cancer cells.
      However, this drug's effect on bladder cancer cells remains largely unknown.
      Here, we report that TZ induced autophagy and enhanced apoptosis in T24 cells.
      Autophagic blockage resulted in the attenuation of TZ-dependent apoptosis.
      Necrostatin-1, an inhibitor of necroptosis, was found to reduce light chain 3
      (LC3)-II accumulation and partially rescue the loss of cell viability induced by
      TZ. It was demonstrated that TZ activated autophagy concurrent with the
      activation of the adenosine monophosphate-dependent protein kinase (AMPK)
      signaling pathway. AMPK inhibition led to a reduction in LC3-II levels, which
      were responsive to TZ treatment. Overall, TZ induced multiple types of programmed
      cell death in bladder cancer cells, and while the autophagy induced by the
      agonist contributed to the apoptotic process, crosstalk or switching between the
      different types of cell death likely occurred. 

PMID- 24853626
TI  - Mini gamma cameras for intra-operative nuclear tomographic reconstruction.
AB  - Nuclear imaging modalities like PET or SPECT are in extensive use in medical
      diagnostics. In a move towards personalized therapy, we present a flexible
      nuclear tomographic imaging system to enable intra-operative SPECT-like 3D
      imaging. The system consists of a miniaturized gamma camera mounted on a robot
      arm for flexible positioning, while spatio-temporal localization is provided by
      an optical tracking system. To facilitate statistical tomographic reconstruction
      of the radiotracer distribution using a maximum likelihood approach, a precise
      model of the mini gamma camera is generated by measurements. The entire system is
      evaluated in a series of experiments using a hot spot phantom, with a focus on
      criteria relevant for the intra-operative workflow, namely the number of required
      imaging positions as well as the required imaging time. The results show that
      high quality reconstructed images of simple hot spot configurations with
      positional errors of less than one millimeter are possible within acquisition
      times as short as 15s. 

PMID- 24853627
TI  - The temporal dynamics of the perceptual consequences of action-effect prediction.
AB  - An essential aspect of voluntary action control is the ability to predict the
      perceptual effects of our actions. Although the influence of action-effect
      prediction on humans' behavior and perception is unequivocal, it remains unclear
      when action-effect prediction is generated by the brain. The present study
      investigates the dynamics of action effect anticipation by tracing the time
      course of its perceptual consequences. Participants completed an acquisition
      phase during which specific actions (left and right key-presses) were associated
      with specific visual effects (upward and downward dots motion). In the test phase
      they performed a 2 AFC identification task in which they were required to
      indicate whether the dots moved upward or downward. To isolate any effects of
      action-effect prediction on perception, participants were presented with
      congruent and incongruent dot motion in which the association participants
      learned in the previous acquisition phase was respected and violated,
      respectively. Crucially, to assess the temporal dynamics of action prediction,
      congruent and incongruent stimuli were presented at different intervals before or
      after action execution. We observed higher sensitivity (d') to motion
      discrimination in congruent vs. incongruent trials only when stimuli were
      presented from about 220ms before the action to 280ms after the action. The
      temporal dynamics of our effect suggest that action-effect prediction modulates
      perception at later stages of motor preparation. 

PMID- 24853628
TI  - Perceiving by proxy: effect-based action control with unperceivable effects.
AB  - Anticipations of future sensory events have the potential of priming motor
      actions that would typically cause these events. Such effect anticipations are
      generally assumed to rely on previous physical experiences of the contingency of
      own actions and their ensuing effects. Here we propose that merely imagined
      action effects may influence behaviour similarly as physically experienced action
      effects do. Three experiments in the response-effect compatibility paradigm show
      that the mere knowledge of action-effect contingencies is indeed sufficient to
      incorporate these effects into action control even if the effects are never
      experienced as causally linked to own actions. The experiments further highlight
      constraints for this mechanism which seems to be rather effortful and to depend
      on explicit intentions. 

PMID- 24853629
TI  - Tolerance for distorted faces: challenges to a configural processing account of
      familiar face recognition.
AB  - Face recognition is widely held to rely on 'configural processing', an analysis
      of spatial relations between facial features. We present three experiments in
      which viewers were shown distorted faces, and asked to resize these to their
      correct shape. Based on configural theories appealing to metric distances between
      features, we reason that this should be an easier task for familiar than
      unfamiliar faces (whose subtle arrangements of features are unknown). In fact,
      participants were inaccurate at this task, making between 8% and 13% errors
      across experiments. Importantly, we observed no advantage for familiar faces: in
      one experiment participants were more accurate with unfamiliars, and in two
      experiments there was no difference. These findings were not due to general task
      difficulty - participants were able to resize blocks of colour to target shapes
      (squares) more accurately. We also found an advantage of familiarity for resizing
      other stimuli (brand logos). If configural processing does underlie face
      recognition, these results place constraints on the definition of 'configural'.
      Alternatively, familiar face recognition might rely on more complex criteria -
      based on tolerance to within-person variation rather than highly specific
      measurement. 

PMID- 24853630
TI  - The development of co-representation effects in a joint task: do children
      represent a co-actor?
AB  - When two adults jointly perform a task, they often show interference effects
      whereby the other's task interferes with their own performance (Sebanz, Knoblich,
      & Prinz, 2003). The current study investigated whether these co-representation
      effects can be observed in young children. This phenomenon can be used as a
      criterion for adult-like joint action in children, which has been under debate in
      existing literature due to the difficulty in identifying what mechanisms underlie
      the behaviours observed (Brownell, 2011). In Experiment 1, two children performed
      an adapted Bear Dragon task (Kochanska, Murray, Jacques, Koenig, & Vandegeest,
      1996), where children were required to point to a picture when instructed to do
      so by one puppet and to inhibit pointing when instructed to by the other. In the
      Same Task condition, both children in a pair were asked to respond to the same
      puppet, whereas in the Different Task condition, they were asked to respond to
      different puppets. Children made more errors in the Different Task condition than
      the Same Task, suggesting that they were experiencing interference from their
      partner's task rule. In Experiment 2 children in Different and Same task
      conditions began with the same task as in Experiment 1 and then switched which
      puppet to respond to. Switch costs were lower in the Different task condition,
      consistent with children having already represented the alternative task rule on
      behalf of their partner during the pre-switch phase. Experiment 3 replicated the
      effect of Task in a novel computer-based paradigm with children between 4 and
      5years, but not younger. These data provide the first direct evidence that
      children as young as 4years co-represent a partner's task during a joint
      activity, and that younger children may not be capable of co-representation. 

PMID- 24853631
TI  - Fabrication of robust hydrogel coatings on polydimethylsiloxane substrates using
      micropillar anchor structures with chemical surface modification.
AB  - A durable hydrophilic and protein-resistant surface of polydimethylsiloxane
      (PDMS) based devices is desirable in many biomedical applications such as
      implantable and microfluidic devices. This paper describes a stable antifouling
      hydrogel coating on PDMS surfaces. The coating method combines chemical
      modification and surface microstructure fabrication of PDMS substrates. Three
      (trimethoxysilyl)propyl methacrylates containing C?C groups were used to modify
      PDMS surfaces with micropillar array structures fabricated by a replica molding
      method. The micropillar structures increase the surface area of PDMS surfaces,
      which facilitates secure bonding with a hydrogel coating compared to flat PMDS
      surfaces. The adhesion properties of the hydrogel coating on PDMS substrates were
      characterized using bending, stretching and water immersion tests. Long-term
      hydrophilic stability (maintaining a contact angle of 55 degrees  for a month)
      and a low protein adsorption property (35 ng/cm(2) of adsorbed BSA-FITC) of the
      hydrogel coated PDMS were demonstrated. This coating method is suitable for PDMS
      modification with most crosslinkable polymers containing C?C groups, which can be
      useful for improving the anti-biofouling performance of PDMS-based biomedical
      microdevices. 

PMID- 24853633
TI  - Saltation transport rate in unsteady wind variations.
AB  - Wind flow in the atmospheric boundary layer is usually turbulent. The gusty wind
      significantly influences the saltation transport which is treated as equilibrium
      saltation. This study performs one-dimension numerical simulations of unsteady
      sand saltation to discuss the effects of parameters of periodical wind variations
      on saltation response and sand transport rate prediction. The results show that
      unsteady transport rates are larger than steady rates of equivalent mean wind
      velocity. The ratio of unsteady/steady transport rates increases with the
      increase of amplitude and frequency. For the average wind velocities much larger
      than the threshold value, the errors of transport rates predicted by unsteady and
      steady model are about 10%, while for a wind velocity slightly larger than
      saltation threshold, the errors will be more than 200%. The sand transport rates
      are not zero even though the average wind velocity equals (is even smaller than)
      the threshold value, whereas Q must be zero in the steady model. Finally, an
      unsteady transport rate prediction formula is proposed which takes mean velocity,
      fluctuating intensity and period as independent variables. 

PMID- 24853634
TI  - Elapsed time for crack formation during drying.
AB  - The drying of colloidal films usually leads to mechanical instabilities that
      affect the uniformity of the final deposit. The resulting patterns are the
      signature of the mechanical stress, and reveal the way the system consolidates.
      We report experimental results on the crack patterns induced by the drying of
      sessile drops of concentrated dispersions. Crack patterns exhibit a well-defined
      spatial order, and a regular temporal periodicity. In addition, the onset of
      cracking occurs after a well-defined elapsed time that depends on the mechanical
      properties of the gel, and on the drying kinetics. The estimation of the time
      elapsed before cracks form is related to the elastic properties of the material.
      This is supported by quantitative measurements using indentation testing and by a
      simple scaling law derived from poro-elastic theory. 

PMID- 24853632
TI  - Interaction, solubilization and location of p-hydroxybenzoic acid and its sodium
      salt in micelles of moderately hydrophilic PEO-PPO-PEO triblock copolymers.
AB  - Micelles of ABA type triblock copolymers (where A is polyethylene oxide PEO and B
      is polypropylene oxide PPO) viz. Pluronic(r) P103, P104 and P105 (each containing
      almost the same PPO mol wt. ~ 3250 g/mol and 30, 40 and 50 wt.% of PEO,
      respectively) in the presence of p -hydroxybenzoic acid (PHBA) and its sodium
      salt (Na-PHBA) were examined by viscosity, dynamic light scattering (DLS), small
      angle neutron scattering (SANS) and NMR. Spherical polymeric micelles (apparent
      hydrodynamic diameter ~ 20 nm) in water at 30  degrees C grow in the presence of
      PHBA and transform into prolate-ellipsoidal shape with an increased aggregation
      number. The micellar transition was favored at higher PHBA concentration,
      temperature and for copolymers with more hydrophobicity. The PHBA salt, however,
      increased cloud point and showed only a marginal decrease in aggregation number
      even at much higher concentrations. The location of PHBA in micelle was
      elucidated by nuclear Overhauser enhancement spectroscopy (NOESY).

PMID- 24853635
TI  - Morphology and growth of polarized tissues.
AB  - We study and classify the time-dependent morphologies of polarized tissues
      subject to anisotropic but spatially homogeneous growth. Extending previous
      studies, we model the tissue as a fluid, and discuss the interplay of the active
      stresses generated by the anisotropic cell division and three types of passive
      mechanical forces: viscous stresses, friction with the environment and tension at
      the tissue boundary. The morphology dynamics is formulated as a free-boundary
      problem, and conformal mapping techniques are used to solve the evolution
      numerically. We combine analytical and numerical results to elucidate how the
      different passive forces compete with the active stresses to shape the tissue in
      different temporal regimes and derive the corresponding scaling laws. We show
      that in general the aspect ratio of elongated tissues is non-monotonic in time,
      eventually recovering isotropic shapes in the presence of friction forces, which
      are asymptotically dominant. 

PMID- 24853637
TI  - From serendipitous assembly to controlled synthesis of 3d-4f single-molecule
      magnets.
AB  - Learning from serendipitous assembly, we have prepared a new family of designed
      3d-4f Mn6Ln complexes. The dynamics of relaxation of the magnetization via
      alternating-current magnetic susceptibility for the new Mn6Ln complexes 1 (Ln =
      La), 2 (Ln = Tb), and 4 (Ln = Dy) have been studied down to 0.2 K. 

PMID- 24853636
TI  - Implications of Look AHEAD for clinical trials and clinical practice.
AB  - Look AHEAD (Action for Health in Diabetes) was a randomized clinical trial
      designed to examine the long-term health effects of weight loss in overweight and
      obese individuals with type 2 diabetes. The primary result was that the incidence
      of cardiovascular events over a median follow-up of 9.6 years was not reduced in
      the Intensive Lifestyle Group relative to the control group. This finding is
      discussed, with emphasis on its implications for design of trials and clinical
      treatment of obese persons with type 2 diabetes.

PMID- 24853638
TI  - Smoking and alcohol abuse are the most preventable risk factors for invasive
      pneumonia and other pneumococcal infections.
AB  - OBJECTIVES: To determine the prevalence of smoking and alcohol abuse among
      patients with invasive pneumococcal disease (IPD) in order to promote prevention
      strategies. METHODS: We prospectively studied all culture-proven IPD cases in
      patients aged >= 18 years during the period 1997-2011. The habits of smoking and
      alcohol abuse were evaluated. Pneumococcal serotyping was performed. RESULTS:
      There were 1378 IPD cases, with a mean age of 61 +/- 17 years; 65% were males.
      Compared to the general population aged 18-64 years, patients with IPD of the
      same age group were more often current smokers (57% vs. 35%, p < 0.001) and
      alcohol abusers (21% vs. 6%, p < 0.001). Among patients with IPD, young adults
      (aged 18-49 vs. 50-64 vs. >= 65 years) were more commonly current smokers (71%
      vs. 40% vs.14%, p < 0.001) and alcohol abusers (23% vs. 18% vs. 6%, p < 0.001).
      Males were more frequently smokers and alcohol abusers than females. Smokers and
      alcohol abusers more often had underlying diseases such as HIV infection and
      chronic liver disease. Pneumonia was more common in smokers and peritonitis in
      alcohol abusers. Alcohol abuse conferred higher mortality. Certain pneumococcal
      serotypes, such as serotypes 1, 8, and 23F, more frequently caused IPD in
      smokers, and serotypes 4, 11A, and 19F in alcohol abusers. CONCLUSIONS: Smoking
      and alcohol abuse are the most preventable risk factors for IPD. Implementing
      smoking and alcohol abuse cessation programs and a pneumococcal vaccination
      schedule are essential to diminish the burden of pneumonia and other pneumococcal
      infections.

PMID- 24853640
TI  - Evolution of epitaxial semiconductor nanodots and nanowires from supersaturated
      wetting layers.
AB  - In this tutorial we review recent progress in the design and growth of epitaxial
      semiconductor nanostructures in lattice-mismatched material systems. We focus on
      the Ge on Si model system after pointing out the similarities to III-V and other
      growth systems qualitatively as well as quantitatively. During material
      deposition, the first layers of the epitaxial film wet the surface before the
      formation of strain-driven three-dimensional nanostructures. In particular, we
      stress that the supersaturation of the wetting layer (WL), whose relevance is
      often neglected, plays a key role in determining the nucleation and growth of
      nanodots (NDs), nanodot-molecules and nanowires (NWs). At elevated growth
      temperatures the Ge reservoir in the planar, supersaturated WL is abruptly
      consumed and generates NDs with highly homogeneous sizes - a process mainly
      driven by elastic energy minimization. Furthermore, the careful control of the
      supersaturated Ge layer allows us to obtain perfectly site-controlled, ordered
      NDs or ND-molecules on pit-patterned substrates for a broad range of pit-periods.
      At low growth temperatures subtle interplays between surface energies of dominant
      crystal facets in the system drive the material transfer from the supersaturated
      WL into the elongating NWs growing horizontally, dislocation- and catalyst-free
      on the substrate surface. Due to the similarities in the formation of
      nanostructures in different epitaxial semiconductor systems we expect that the
      observation of the novel growth phenomena described in this Tutorial Review for
      Ge/Si should be relevant for other lattice-mismatched heterostructure systems,
      too. 

PMID- 24853641
TI  - Synthesis of macroporous polymer particles using reactive gelation under shear.
AB  - By combining elements from colloidal and polymer reaction engineering a new
      approach toward macroporous, mechanically robust polymer particles is presented,
      which does not require any porogenic additives. Specifically, aggregation and
      breakage in turbulent conditions of aggregates originating from fully
      destabilized primary latex particles is applied to produce compact, micrometer
      sized clusters. Post-polymerization of monomer introduced initially to swell the
      primary particles is imparting mechanical rigidity and permanence to the internal
      structure. The resulting microclusters exhibit an internal porosity on the order
      of 70% and relatively broad pore size distribution, with exceptionally large
      pores, ranging from about 50 nm to 10 MUm in diameter. These particulate
      microclusters, produced via reactive gelation under shear, are fractal objects
      with fractal dimension around 2.7, as opposed to the more open fractal structure
      of a monolith produced via stagnant reactive gelation, with fractal dimension of
      1.9. Such macroporous particles are thought to be useful in applications
      requiring pores on the micrometer scale, e.g., in the chromatography of
      biomolecules or for packing beds perfusive to convective flow. 

PMID- 24853639
TI  - Mobile elements drive recombination hotspots in the core genome of Staphylococcus
      aureus.
AB  - Horizontal gene transfer is an important driver of bacterial evolution, but
      genetic exchange in the core genome of clonal species, including the major
      pathogen Staphylococcus aureus, is incompletely understood. Here we reveal
      widespread homologous recombination in S. aureus at the species level, in
      contrast to its near-complete absence between closely related strains. We
      discover a patchwork of hotspots and coldspots at fine scales falling against a
      backdrop of broad-scale trends in rate variation. Over megabases, homoplasy rates
      fluctuate 1.9-fold, peaking towards the origin-of-replication. Over kilobases, we
      find core recombination hotspots of up to 2.5-fold enrichment situated near fault
      lines in the genome associated with mobile elements. The strongest hotspots
      include regions flanking conjugative transposon ICE6013, the staphylococcal
      cassette chromosome (SCC) and genomic island nuSaalpha. Mobile element-driven
      core genome transfer represents an opportunity for adaptation and challenges our
      understanding of the recombination landscape in predominantly clonal pathogens,
      with important implications for genotype-phenotype mapping. 

PMID- 24853642
TI  - Gelatin-siloxane nanoparticles to deliver nitric oxide for vascular cell
      regulation: synthesis, cytocompatibility, and cellular responses.
AB  - Nitric oxide (NO) is an important mediator in cardiovascular system to regulate
      vascular tone and maintain tissue homeostasis. Its role in vascular cell
      regulation makes it promising to address the post-surgery restenosis problem.
      However, the application of NO is constrained by its high reactivity. Here, we
      developed a novel NO-releasing gelatin-siloxane nanoparticle (GS-NO NP) to
      deliver NO effectively for vascular cell regulation. Results showed that gelatin
      siloxane nanoparticles (GS NPs) could be synthesized via sol-gel chemistry with a
      diameter of ~200 nm. It could be modified into GS-NO NPs via S-nitrosothiol
      (RSNO) modification. The synthesized GS-NO NPs could release a total of ~0.12
      umol/mg NO sustainably for 7 days following a first-order exponential profile.
      They showed not only excellent cytocompatibility, but also rapid
      intracellularization within 2 h. GS-NO NPs showed inhibition of human aortic
      smooth muscle cell (AoSMC) proliferation and promotion of human umbilical vein
      endothelial cell (HUVEC) proliferation in a dose-dependent manner, which is an
      important approach to prevent restenosis. With GS-NO NP dose at 100 ug/mL, the
      proliferation of AoSMCs could be slowed down whereas the growth of HUVECs was
      significantly promoted. We concluded that GS-NO NPs could have potential to be
      used as a promising nano-system to deliver NO for vascular cell regulation.

PMID- 24853643
TI  - Effect of fat on serum 25-hydroxyvitamin D levels after a single oral dose of
      vitamin D in young healthy adults: a double-blind randomized placebo-controlled
      study.
AB  - PURPOSE: This double-blind placebo-controlled trial evaluated serum 25
      hydroxyvitamin D [25(OH)D] levels after the oral intake of a single dose of
      cholecalciferol during one of the three meals, containing different amounts of
      fat or placebo. METHODS AND RESULTS: Sixty-four healthy medical residents or
      students of a university hospital in Porto Alegre, latitude 30 degrees  S,
      Brazil, were divided into four groups. Three groups received a single 50,000 IU
      oral dose of cholecalciferol during a meal containing 0 g (Group 1), 15 g (Group
      2) or 30 g (Group 3) of fat, and one group received placebo (Group 4), according
      to randomization. Serum 25(OH)D, parathyroid hormone, total calcium, albumin,
      magnesium, and creatinine levels, and urinary calcium, magnesium, and creatinine
      levels were measured at baseline and after 14 days. Baseline mean serum 25(OH)D
      levels were low in all groups. Vitamin D given during breakfast increased the
      mean change of serum 25(OH)D levels, when compared to placebo. Furthermore, the
      intake of fat with vitamin D increased the mean change of serum 25(OH)D levels.
      CONCLUSION: A single oral dose of vitamin D given with food increased mean serum
      25(OH)D levels, after 2 weeks, and the mean increase was larger, when the meal
      had at least 15 g of fat. These findings can have important implications to oral
      vitamin D supplementation.

PMID- 24853645
TI  - Total synthesis of (+)-ileabethoxazole via an iron-mediated Pauson-Khand [2 + 2 +
      1] carbocyclization.
AB  - Studies describe the total synthesis of (+)-ileabethoxazole (1) using a Stille
      cross-coupling reaction of propargylic stannanes with 5-iodo-1,3-oxazoles to
      produce 1,1-disubstituted allenes (11). An iron-mediated [2 + 2 + 1]
      carbocyclization yields a novel cyclopentenone for elaboration to 1. Site
      selective palladium insertion reactions allow for regiocontrolled substitutions
      of the heterocycle. Asymmetric copper hydride reductions are examined, and
      strategies for the formation of the central aromatic ring are discussed. 

PMID- 24853646
TI  - Phytohormone signaling in arbuscular mycorhiza development.
AB  - To establish arbuscular mycorhiza (AM) symbiosis glomeromycotan fungi colonize
      the interior of roots. This process is associated with developmental changes of
      root cells as well as fungal hyphae. The formation of fungal colonization
      structures and the extent of root colonization are largely under plant control,
      depending on environmental conditions and the resulting physiological state of
      the host. Phytohormone signaling pathways are currently emerging as important
      regulators of AM development. Root exuded strigolactones activate AM fungi before
      colonization and a host strigolactone receptor component is required for AM
      development. Auxin quantitatively influences AM colonization and might perform an
      additional cell-autonomous function in the promotion of arbuscule development.
      Gibberellin signaling inhibits AM and conversely DELLA proteins are required for
      AM formation. Given the importance of phytohormone signaling in plant
      developmental responses to the environment it can be predicted that elucidating
      how phytohormones regulate AM development will provide a lead into understanding
      how plants orchestrate AM symbiosis with their physiological needs under changing
      environmental conditions.

PMID- 24853644
TI  - What triggers the rising of an intraspecific biodiversity hotspot? Hints from the
      agile frog.
AB  - Hotspots of genetic diversity are regions of utmost importance for species
      survival and conservation, and their intimate link with the geographic location
      of glacial refugia has been well established. Nonetheless, the microevolutionary
      processes underlying the generation of hotspots in such regions have only
      recently become a fervent field of research. We investigated the phylogeographic
      and population genetic structure of the agile frog, Rana dalmatina, within its
      putative refugium in peninsular Italy. We found this region to harbour far more
      diversity, phylogeographic structure, and lineages of ancient origin than that by
      the rest of the species' range in Europe. This pattern appeared to be well
      explained by climate-driven microevolutionary processes that occurred during both
      glacial and interglacial epochs. Therefore, the inferred evolutionary history of
      R. dalmatina in Italy supports a view of glacial refugia as 'factories' rather
      than as repositories of genetic diversity, with significant implications for
      conservation strategies for hotspots. 

PMID- 24853647
TI  - Supplementary motor area (SMA) volume is associated with psychotic aberrant motor
      behaviour of patients with schizophrenia.
AB  - We aimed to investigate whether aberrant motor behavior in schizophrenia was
      associated with structural alterations in the motor system. Whole brain voxel
      based morphometry of patients with different severity of motor symptoms
      identified altered gray matter volume in the supplementary motor area (SMA), a
      key region of the motor system. 

PMID- 24853648
TI  - The effect of TC14012 on alkali burn-induced corneal neovascularization in mice.
AB  - AIMS: To observe the effect of TC14012 (a CXCR4 antagonist and CXCR7 agonist) on
      alkali burn-induced corneal neovascularization (CNV) in a mouse model. METHODS:
      CNV was induced in vivo by alkali burns on the corneas of BALB/c mice. A total of
      54 mice treated with alkali burns were randomly divided into 3 groups, each of
      which received one of the following treatments: bilateral subconjunctival
      injections of TC14012 for 3 consecutive days, bilateral subconjunctival
      injections of balanced saline (BS) for 3 consecutive days or no treatment (blank
      control). The areas of CNV were measured on days 3, 7 and 14 after the alkali
      burns. CXCR4, CXCR7, vascular endothelial growth factor (VEGF) and matrix
      metalloproteinase (MMP) mRNAs were detected and quantified by real-time reverse
      transcription PCR on days 7 and 14. Additionally, the expression of the proteins
      CXCR4, CXCR7, VEGF, beta-arrestin 2, total ERK1/2 and phospho-ERK1/2 was
      determined by Western blotting. RESULTS: On day 7 after the alkali burns, the CNV
      area, VEGF, MMP-2 and MMP-9 mRNA levels, and VEGF, beta-arrestin 2 and phospho
      ERK1/2 protein levels were increased in the TC14012 group compared with the
      nontreatment and BS groups. However, on day 14, the CNV area, CXCR4, CXCR7, VEGF,
      MMP-2 and MMP-9 mRNA levels, and the CXCR4, CXCR7, VEGF and beta-arrestin 2
      protein levels were significantly decreased in the TC14012 group. CONCLUSIONS:
      TC14012 initially enhanced alkali burn-induced CNV but reduced CNV in later
      stages. In addition to CXCR4, CXCR7 is involved in the pathogenesis of CNV.

PMID- 24853649
TI  - Microfluidic strategies for design and assembly of microfibers and nanofibers
      with tissue engineering and regenerative medicine applications.
AB  - Fiber-based materials provide critical capabilities for biomedical applications.
      Microfluidic fiber fabrication has recently emerged as a very promising route to
      the synthesis of polymeric fibers at the micro and nanoscale, providing fine
      control over fiber shape, size, chemical anisotropy, and biological activity.
      This Progress Report summarizes advanced microfluidic methods for the fabrication
      of both microscale and nanoscale fibers and illustrates how different methods are
      enabling new biomedical applications. Microfluidic fabrication methods and
      resultant materials are explained from the perspective of their microfluidic
      device principles, including co-flow, cross-flow, and flow-shaping designs. It is
      then detailed how the microchannel design and flow parameters influence the
      variety of synthesis chemistries that can be utilized. Finally, the integration
      of biomaterials and microfluidic strategies is discussed to manufacture unique
      fiber-based systems, including cell scaffolds, cell encapsulation, and woven
      tissue matrices. 

PMID- 24853650
TI  - Effects of electroconvulsive therapy and magnetic seizure therapy on acute memory
      retrieval.
AB  - OBJECTIVES: Electroconvulsive therapy (ECT) is currently the most effective
      treatment for severe depression. However, it is frequently associated with
      negative cognitive side effects. Magnetic seizure therapy (MST) depicts an
      alternative, although experimental, convulsive treatment for major depression.
      Initial results suggest comparable antidepressant effects accompanied by a better
      side effect profile. However, no studies up to now have addressed acute retrieval
      disruption after MST in comparison to ECT. Therefore, we intended to broaden
      insight into the side effect profile of MST compared to ECT by examining the
      disruption of acute verbal memory processes after treatment. METHODS: Twenty
      depressed patients were randomly assigned to either MST (10 patients) or ECT (10
      patients) treatment. On 2 treatment days and 2 treatment-free days, the patients
      memorized words using a controlled learning paradigm derived from the Batchelder
      and Riefer storage retrieval model. Four hours after memorization, the patients
      were asked to retrieve words freely (delayed recall) and a second time with the
      help of an additional cue constructed out of a hypernymic category (cued recall).
      By comparing memory performance on treatment days to control days, treatment
      induced memory disruption was evaluated. RESULTS: After ECT, delayed recall was
      disturbed, whereas after MST, it was not. However, this difference in performance
      was no longer apparent upon cue application (cued recall). CONCLUSIONS: This
      study demonstrates that ECT-induced acute memory disruption measured by delayed
      recall is absent after MST, confirming its superior side effect profile. We hope
      that confirming advantages of MST over ECT will improve therapy options for
      patients with severe depression.

PMID- 24853651
TI  - The development of partnership after hypertensive diseases in pregnancy.
AB  - OBJECTIVE: Hypertensive diseases in pregnancy (HDP) occur in 5-8% of all
      pregnancies and represent one of the most important causes of maternal and fetal
      morbidity. Even after a normal pregnancy/delivery adaptation to parenthood is a
      major challenge. However, a successful adjustment is important for future family
      health. As pregnancy complications may put additional strain on early parenthood,
      the current study investigated satisfaction with partnership including factors
      which determine (dis)satisfaction as well as separation rates after pregnancies
      complicated by HDP. METHODS: A total of 737 women after HDP and 624 matched
      control women completed a self-administered questionnaire on psycho-social
      factors in the development of HDP. Free-text answers on satisfaction with
      partnership were analyzed by conceptual analysis. RESULTS: Women with HDP were
      significantly less often satisfied with their partnership than control women
      (76%/81.1%; p < 0.05). Women with preeclampsia were at higher risk for an
      unsatisfactory relationship than those with other manifestations of HDP. Common
      interests and aims could be identified as the most important reasons for a
      satisfying marital relationship in women with and without a diagnosis of HDP.
      CONCLUSION: HDP represent an additional challenge in family adjustment. Adapted
      perinatal psycho-social support may help to facilitate the start into family
      life.

PMID- 24853652
TI  - Urodynamic studies for management of urinary incontinence in children and adults:
      A short version Cochrane systematic review and meta-analysis.
AB  - BACKGROUND: Urodynamic tests are used to investigate people who have urinary
      incontinence or other urinary symptoms in order to make an objective diagnosis.
      The investigations are invasive and time consuming. OBJECTIVES: To determine if
      treatment according to a urodynamic-based diagnosis, compared to treatment based
      on history and examination, leads to more effective clinical care and better
      clinical outcomes. SEARCH METHODS: Cochrane Incontinence Group Specialized
      Register (searched February 19, 2013); reference lists of relevant articles.
      SELECTION CRITERIA: Randomized and quasi-randomized trials in people who were and
      were not investigated using urodynamics, or comparing one type of urodynamic test
      against another. DATA COLLECTION AND ANALYSIS: At least two independent review
      authors carried out trial assessment, selection, and data abstraction. RESULTS:
      We found eight trials but data were available for only 1,036 women in seven
      trials. Women undergoing urodynamics were more likely to have their management
      changed (17% vs. 3%, risk ratio [RR] 5.07, 95% CI 1.87-13.74). Two trials
      suggested that women were more likely to receive drugs (RR 2.09, 95% CI 1.32
      3.31), but, in five trials, women were not more likely to undergo surgery (RR
      0.99, 95% CI 0.88-1.12). There was no statistically significant difference in
      urinary incontinence in women who had urodynamics (37%) compared with those
      undergoing history and clinical examination alone (36%) (RR 1.02, 95% CI 0.86
      1.21). AUTHORS' CONCLUSIONS: While urodynamics did change clinical decision
      making, there was some high-quality evidence that this did not result in lower
      urinary incontinence rates after treatment.

PMID- 24853653
TI  - Upon the photostability of 8-nitro-cGMP and its caging as a 7
      dimethylaminocoumarinyl ester.
AB  - 8-Nitro-cGMP was recently discovered as a second messenger of nitric oxide. We
      describe here the synthesis and properties of DMACM-modified 8-nitro-cGMP for
      photochemical uncaging. Owing to the limited photostability of 8-nitro-cGMP care
      must be taken, but the photorelease of the intact product was readily feasible.
      Unexpectedly, 8-nitro-cGMP decays under formation of 8-nitrosoguanine when
      irradiated with light. 

PMID- 24853654
TI  - Faster-than-anticipated Na(+)/Cl(-) diffusion across lipid bilayers in vesicles.
AB  - Maintenance of electrochemical potential gradients across lipid membranes is
      critical for signal transduction and energy generation in biological systems.
      However, because ions with widely varying membrane permeabilities all contribute
      to the electrostatic potential, it can be difficult to measure the influence of
      diffusion of a single ion type across the bilayer. To understand the
      electrodiffusion of H(+) across lipid bilayers, we used a pH-sensitive
      fluorophore to monitor the lumenal pH in vesicles after a stepwise change in the
      bulk pH. In vesicles containing the ion channel gramicidin, the lumenal pH
      rapidly approached the external pH. In contrast, the lumen of intact vesicles
      showed a two stage pH response: an initial rapid change occurred over ~1min,
      followed by a much slower change over ~24h. We provide a quantitative
      interpretation of these results based on the Goldman-Hodgkin-Katz ion fluxes
      discharging the electrical capacitance of the bilayer membrane. This
      interpretation provides an estimate of the permeability of the membranes to Na(+)
      and Cl(-) ions of ~10(-8)cm/s, which is ~3 orders of magnitude faster than
      previous reports. We discuss possible mechanisms to account for this considerably
      higher permeability in vesicle membranes. 

PMID- 24853655
TI  - The role of spontaneous lipid curvature in the interaction of interfacially
      active peptides with membranes.
AB  - Research on antimicrobial peptides is in part driven by urgent medical needs such
      as the steady increase in pathogens being resistant to antibiotics. Despite the
      wealth of information compelling structure-function relationships are still
      scarce and thus the interfacial activity model has been proposed to bridge this
      gap. This model also applies to other interfacially active (membrane active)
      peptides such as cytolytic, cell penetrating or antitumor peptides. One parameter
      that is strongly linked to interfacial activity is the spontaneous lipid
      curvature, which is experimentally directly accessible. We discuss different
      parameters such as H-bonding, electrostatic repulsion, changes in monolayer
      surface area and lateral pressure that affect induction of membrane curvature,
      but also vice versa how membrane curvature triggers peptide response. In
      addition, the impact of membrane lipid composition on the formation of curved
      membrane structures and its relevance for diverse mode of action of interfacially
      active peptides and in turn biological activity are described. This article is
      part of a Special Issue entitled: Interfacially Active Peptides and Proteins.
      Guest Editors: William C. Wimley and Kalina Hristova. 

PMID- 24853656
TI  - Biophysical investigations of the structure and function of the tear fluid lipid
      layers and the effect of ectoine. Part B: artificial lipid films.
AB  - The tear fluid lipid layer is present at the outermost part of the tear film
      which lines the ocular surface and functions to maintain the corneal surface
      moist by retarding evaporation. Instability in the structure of the tear fluid
      lipid layer can cause an increased rate of evaporation and thus dry eye syndrome.
      Ectoine has been previously shown to fluidize lipid monolayers and alter the
      phase behavior. In the current study we have investigated the effect of ectoine
      on the artificial tear fluid lipid layer composed of binary and ternary lipid
      mixtures of dipalmitoyl phosphatidylcholine (DPPC), cholesteryl esters and tri
      acyl-glycerols. The focus of our study was mainly the structural and the
      biophysical aspects of the artificial tear fluid lipid layer using surface
      activity studies and topology analysis. The presence of ectoine consistently
      causes an expansion of the pressure-area isotherm indicating increased
      intermolecular spacing. The topology studies showed the formation of droplet-like
      structures due to the addition of ectoine only when tri-acyl-glycerol is present
      in the mixture of DPPC and chol-palmitate, similar to the natural meibomian
      lipids. Consequently, the hypothesis of an exclusion of tri/di-acyl-glycerol from
      the meibomian lipid film in the presence of ectoine in the subphase is confirmed.
      A model describing the effect of ectoine on meibomian lipid films is further
      presented which may have an application for the use of ectoines in eye drops as a
      treatment for the dry eye syndrome. 

PMID- 24853657
TI  - Characterizing the structure of lipodisq nanoparticles for membrane protein
      spectroscopic studies.
AB  - Membrane protein spectroscopic studies are challenging due to the difficulty
      introduced in preparing homogenous and functional hydrophobic proteins
      incorporated into a lipid bilayer system. Traditional membrane mimics such as
      micelles or liposomes have proved to be powerful in solubilizing membrane
      proteins for biophysical studies, however, several drawbacks have limited their
      applications. Recently, a nanosized complex termed lipodisq nanoparticles was
      utilized as an alternative membrane mimic to overcome these caveats by providing
      a homogeneous lipid bilayer environment. Despite all the benefits that lipodisq
      nanoparticles could provide to enhance the biophysical studies of membrane
      proteins, structural characterization in different lipid compositions that
      closely mimic the native membrane environment is still lacking. In this study,
      the formation of lipodisq nanoparticles using different weight ratios of
      POPC/POPG lipids to SMA polymers was characterized via solid-state nuclear
      magnetic resonance (SSNMR) spectroscopy and dynamic light scattering (DLS). A
      critical weight ratio of (1/1.25) for the complete solubilization of POPC/POPG
      vesicles has been observed and POPC/POPG vesicles turned clear instantaneously
      upon the addition of the SMA polymer. The size of lipodisq nanoparticles formed
      from POPC/POPG lipids at this weight ratio of (1/1.25) was found to be about 30
      nm in radius. We also showed that upon the complete solubilization of POPC/POPG
      vesicles by SMA polymers, the average size of the lipodisq nanoparticles is
      weight ratio dependent, when more SMA polymers were introduced, smaller lipodisq
      nanoparticles were obtained. The results of this study will be helpful for a
      variety of biophysical experiments when specific size of lipid disc is required.
      Further, this study will provide a proper path for researchers working on
      membrane proteins to obtain pertinent structure and dynamic information in a
      physiologically relevant membrane mimetic environment.

PMID- 24853658
TI  - Langmuir monolayer studies of the interaction of monoamphiphilic pentacyclic
      triterpenes with anionic mitochondrial and bacterial membrane phospholipids -
      searching for the most active terpene.
AB  - The interactions of three representative monoamphiphilic pentacyclic triterpenes
      (PTs) with cardiolipins (CL) and phosphatidylglycerols (PG) extracted from
      mitochondrial and bacterial membranes were comparatively characterized in binary
      Langmuir monolayers. The studied terpenes: lupeol, alpha- and beta-amyrin are
      isomeric compounds known from their broad biological activity. Anticancer and
      antimicrobial activity of PTs is often correlated with their propensity of being
      incorporated into mitochondrial and bacterial membranes and their specific
      interactions with cardiolipins. In our studies on 18 model systems surface
      pressure (pi)-mean molecular area (A) isotherms were registered at five different
      component proportions in each system. Thermodynamic analysis complemented by in
      situ Brewster angle microscopy visualization of the investigated mixed films
      enabled the thorough characterization of the studied systems. It turned out that
      the investigated terpenes interact more favorably with PG molecules as compared
      to CLs. For most of the system containing CLs the values of DeltaG(exc) were
      positive which was interpreted as the ability of the terpenes to disintegrate the
      membranes rich in CLs. Our results confirmed also that in the light of
      thermodynamic criterion alpha-amyrin exhibited the highest potential to
      disintegrate the CL containing domains in mitochondrial and bacterial membranes.
      The probable origin of the observed specific interactions between alpha-amyrin
      and investigated phospholipids could be explained based on the phenomenon of
      chiral discrimination. The obtained results were also widely discussed in
      reference to the biological activity of the studied compounds. 

PMID- 24853659
TI  - Delineation of the dynamic properties of individual lipid species in native and
      synthetic pulmonary surfactants.
AB  - Pulmonary surfactant (PS) is characterized by a highly conserved lipid
      composition and the formation of unique multilamellar structures within the lung.
      An unusually high concentration of DPPC is a hallmark of PS and is critical to
      the formation of a high surface area, stable air/water interface; the unusual
      lipid polymorphisms observed in PS are dependent on surfactant proteins,
      particularly lung surfactant protein B (SP-B). The molecular mechanisms of lipid
      trafficking and assembly in PS remain largely uncharacterized. Using (2)H and
      (31)P NMR, we characterize the dynamics and polymorphisms of the major lipid
      species in native PS and synthetic lipid mixtures as a function of SP-B1-25
      addition. Our findings point to increased dynamics and a departure from a
      lamellar behavior for DPPC on addition of the peptide, consistent with our
      observations of DPPC phase separation in native surfactant. The monounsaturated
      lipids POPC, POPG and POPE remain in a lamellar phase and are less affected than
      DPPC by surfactant peptide addition. Additionally, we demonstrate that the
      properties of a native PS can be successfully mimicked by using a fully synthetic
      lipid mixture allowing the efficient evaluation of peptidomimetics under
      development for PS replacement therapies via NMR spectroscopy. The specificity of
      the dynamic changes in DPPC relative to POPC suggests the importance of tuning
      partitioning properties in successful peptidomimetic design.

PMID- 24853660
TI  - Validation of Krathom (Mitragyna speciosa Korth.) Dependence Scale (KDS): a
      dependence screen for internationally emerging psychoactive substance.
AB  - BACKGROUND: Krathom (Mitragyna speciosa Korth.) is the most commonly used illicit
      substance in Thailand, and its use has become widespread internationally. Studies
      on krathom dependence and its health impact are scarce, as there has been no
      instrument to measure its dependence syndrome and classify krathom users. This
      study aimed to develop and explore the factor structure, reliability, and
      validity of a Krathom Dependence Scale (KDS). METHODS: This study comprised 2
      phases. First, cross-sectional surveys were conducted with 523 (Phase I) and 595
      (Phase II) male villagers aged >25 years who were regular, occasional, ex-, or
      nonusers of krathom. Scale construction was based on the qualitative results from
      users and previous literature. Exploratory factor analysis (EFA) using maximum
      likelihood extraction with oblimin rotation was conducted in Phase I and
      confirmatory factor analysis (CFA) in Phase II to confirm the construct of the
      scale. Internal consistency of the KDS was assessed using Cronbach's alpha
      coefficient. Discriminative validity was examined by checking its ability to
      differentiate between regular and occasional users and patterns of krathom use
      and its concurrent validity by comparing its levels of score with the Fagerstrom
      Test for Nicotine Dependence (FTND). The KDS contains 16 items on a 0-3 (never
      always) rating scale, making a total score of 0-48. RESULTS: Phase I EFA revealed
      a single-factor solution for the scale, which was confirmed by the CFA in Phase
      II, with an alpha coefficient of .98. The KDS discriminates regular from
      occasional users reasonably well and is highly correlated with the FTND score.
      Two cutoffs were suggested: 34/35 for distinguishing moderate from high
      dependence and 13/14 for low from moderate. CONCLUSIONS: The KDS appears to
      capture key theoretical constructs and correlates with indices of drug dependence
      by standard criteria. It should be useful in early intervention for those with
      krathom use disorders in community and primary care settings.

PMID- 24853661
TI  - Short-term effects of oral administration of Pistacia lentiscus oil on tissue
      specific toxicity and drug metabolizing enzymes in mice.
AB  - BACKGROUND: Pistacia lentiscus (Anacardiaceae) is a flowering plant traditionally
      used in the treatment of various skin, respiratory, and gastrointestinal
      disorders. The aim of this study was to assess whether Pistacia lentiscus oil has
      any short term toxic effects in vivo and in vitro. METHODS: Pistacia lentiscus
      oil (100ul) was administered orally into mice for 5 days. RESULTS: Measurements
      of body weight did not show any weight loss. Serum concentration of LDH did not
      show any significant statistical difference when compared to control mice.
      Similarly, blood, kidney or liver function tests showed no toxicity with Pistacia
      lentiscus oil when compared to the control group. Examination of gastrointestinal
      tissues sections revealed similar structural features with no difference in cell
      proliferation. In this context, pharmacological dilutions of Pistacia lentiscus
      oil (10(-6) - 10(-3)) did not affect the viability (cell death and proliferation)
      of mouse gastric stem cells, human colorectal cancer cells HT29, human hepatoma
      cells HepG2. However, it appears that at the dose and time point studied,
      Pistacia lentiscus oil treatment has targeted various cytochrome P450s and has
      specifically inhibited the activities and the expression of CYP2E1, CYP3A4,
      CYP1A1 and CYP1A2 differentially in different tissues. Our results also
      demonstrate that there is no appreciable effect of Pistacia lentiscus oil on the
      GSH-dependent redox homoeostasis and detoxification mechanism in the tissues.
      CONCLUSION: These data suggest a good safety profile of short term oral use of
      Pistacia lentiscus oil as a monotherapy in the treatment of various skin,
      respiratory, and gastrointestinal disorders. However, due to its inhibitory
      effect of various cytochrome P450s and mainly CYP3A4, this might have
      implications on the bioavailability and metabolism of drugs taken in combination
      with Pistacia lentiscus oil. More attention is needed when Pistacia lentiscus oil
      is intended to be uses in combination with other pharmacological agents in order
      to avoid potential drug-drug interaction leading to toxicity. This study will
      help in safer use of Pistacia lentiscus oil for therapeutic purpose.

PMID- 24853662
TI  - Aryloxymaleimides for cysteine modification, disulfide bridging and the dual
      functionalization of disulfide bonds.
AB  - Tuning the properties of maleimide reagents holds significant promise in
      expanding the toolbox of available methods for bioconjugation. Herein we describe
      aryloxymaleimides which represent 'next generation maleimides' of attenuated
      reactivity, and demonstrate their ability to enable new methods for protein
      modification at disulfide bonds. 

PMID- 24853663
TI  - Predictive and prognostic value of the 21-gene recurrence score in hormone
      receptor-positive, node-positive breast cancer.
AB  - The addition of adjuvant chemotherapy to hormonal therapy is recommended for
      patients with estrogen receptor-positive (ER+), node-positive (N+) early breast
      cancer (EBC). Some of these patients, however, are not likely to benefit from
      treatment and may, therefore, be overtreated while also incurring unnecessary
      treatment-related adverse events and health care costs. The 21-gene Recurrence
      Score assay has been clinically validated and recommended for use in patients
      with ER+, node-negative (N0) EBC to assess the 10-year risk of distant disease
      recurrence and predict the likelihood of response to adjuvant chemotherapy. A
      growing body of evidence from several large phase III clinical trials reports
      similar findings in patients with ER+, N+ EBC. A systematic review of published
      literature from key clinical trials that have used the 21-gene breast cancer
      assay in patients with ER+, N+ EBC was performed. The Recurrence Score has been
      shown to be an independent predictor of disease-free survival, overall survival,
      and distant recurrence-free interval in patients with ER+, N+ EBC. Outcomes from
      decision impact and health economics studies further indicate that the Recurrence
      Score affects physician treatment recommendations equally in patients with N+ or
      N0 disease. It also indicates that a reduction in Recurrence Score-directed
      chemotherapy is cost-effective. There is a large body of evidence to support the
      use of the 21-gene assay Recurrence Score in patients with N+ EBC. Use of this
      assay could help guide treatment decisions for patients who are most likely to
      receive benefit from chemotherapy. 

PMID- 24853664
TI  - The barley anion channel, HvALMT1, has multiple roles in guard cell physiology
      and grain metabolism.
AB  - The barley (Hordeum vulgare) gene HvALMT1 encodes an anion channel in guard cells
      and in certain root tissues indicating that it may perform multiple roles. The
      protein localizes to the plasma membrane and facilitates malate efflux from cells
      when constitutively expressed in barley plants and Xenopus oocytes. This study
      investigated the function of HvALMT1 further by identifying its tissue-specific
      expression and by generating and characterizing RNAi lines with reduced HvALMT1
      expression. We show that transgenic plants with 18-30% of wild-type HvALMT1
      expression had impaired guard cell function. They maintained higher stomatal
      conductance in low light intensity and lost water more rapidly from excised
      leaves than the null segregant control plants. Tissue-specific expression of
      HvALMT1 was investigated in developing grain and during germination using
      transgenic barley lines expressing the green fluorescent protein (GFP) with the
      HvALMT1 promoter. We found that HvALMT1 is expressed in the nucellar projection,
      the aleurone layer and the scutellum of developing barley grain. Malate release
      measured from isolated aleurone layers prepared from imbibed grain was
      significantly lower in the RNAi barley plants compared with control plants. These
      data provide molecular and physiological evidence that HvALMT1 functions in guard
      cells, in grain development and during germination. We propose that HvALMT1
      releases malate and perhaps other anions from guard cells to promote stomatal
      closure. The likely roles of HvALMT1 during seed development and grain
      germination are also discussed. 

PMID- 24853665
TI  - Genetic testing for sporadic hearing loss using targeted massively parallel
      sequencing identifies 10 novel mutations.
AB  - The genetic heterogeneity of non-syndromic hearing loss (NSHL) has hampered the
      identification of its pathogenic mutations. Several recent studies applied
      targeted genome enrichment (TGE) and massively parallel sequencing (MPS) to
      simultaneously screen a large set of known hearing loss (HL) genes. However, most
      of these studies were focused on familial cases. To evaluate the effectiveness of
      TGE and MPS on screening sporadic NSHL patients, we recruited 63 unrelated
      sporadic NSHL probands, who had various levels of HL and were excluded for
      mutations in GJB2, MT-RNR1, and SLC26A4 genes. TGE and MPS were performed on 131
      known HL genes using the Human Deafness Panel oto-DA3 (Otogenetics Corporation.,
      Norcross, GA). We identified 14 pathogenic variants in STRC, CATSPER2, USH2A,
      TRIOBP, MYO15A, GPR98, and TMPRSS3 genes in eight patients (diagnostic rate =
      12.7%). Among these variants, 10 were novel compound heterozygous mutations. The
      identification of pathogenic mutations could predict the progression of HL, and
      guide diagnosis and treatment of the disease.

PMID- 24853666
TI  - Pudendal and median nerve sensory perception threshold: a comparison between
      normative studies.
AB  - BACKGROUND: For the evaluation of sensory innervation, normative data are
      necessary as a comparison. AIMS: To compare our current perception thresholds
      (CPTs) with normative data from other research. METHODS: Healthy volunteers were
      assessed for 2000, 250, and 5 Hz CPTs of the median and pudendal nerve and data
      were compared with other studies. RESULTS: Normative data in the studied group n
      = 41 (male: 21; female: 20) for the median nerve, 2 kHz, 250 Hz, and 5 Hz were
      respectively: 241.85 +/- 67.72 (140-444); 106.27 +/- 39.12 (45-229); 82.05 +/-
      43.40 (13-271). Pudendal nerve CPTs 250 Hz were: 126.44 +/- 69.46 (6-333). For
      men 2 kHz: 349.95 +/- 125.76 (100-588); 5 Hz: 132.67 +/- 51.81 (59-249) and women
      2 kHz:226.20 +/- 119.65 (64-528); 5 Hz: 92.45 +/- 44.66 (35-215). For the median
      nerve no statistical differences for gender were shown. For the pudendal nerve,
      only 250 Hz showed no difference for gender (t-test: 0.516). Comparison of our
      data with CPTs of other normative data showed no agreement for the pudendal
      nerve. For the median nerve only 2 kHz showed agreement in three studies and for
      5 Hz with one study. CONCLUSION: Comparing normative data of multiple studies
      shows a variety of results and poor agreement. Therefore, referring to normative
      data of other studies should be handled with caution.

PMID- 24853667
TI  - Giant cell arteritis presenting with bilateral orbital inflammatory disease and
      enhancing superficial temporal arteries.

PMID- 24853668
TI  - Reporting Guidelines.

PMID- 24853669
TI  - Retraction of "Effects of High-Frequency Repetitive Transcranial Magnetic
      Stimulation on Motor and Gait Improvement in Incomplete Spinal Cord Injury
      Patients".
AB  - Kumru H, Benito J, Murillo N, et al. Effects of high-frequency repetitive
      transcranial magnetic stimulation on motor and gait improvement in incomplete
      spinal cord injury patients. Neurorehabil & Neural Repair 2013;27:421-429.
      Original DOI: 10.1177/1545968312471901.

PMID- 24853670
TI  - Characterization of mouse mediastinal fat-associated lymphoid clusters.
AB  - The association between adipose tissue and immunity has been established and fat
      associated lymphoid clusters (FALCs) are considered as a source of immune cells.
      We discovered lymphoid clusters (LCs) in mouse mediastinal fat tissues (MFTs). In
      Th1-biased C57BL/6N (B6), Th2-biased DBA/2Cr (DBA) and autoimmune-prone MRL/MpJ
      (MRL) mice strains, LCs without a fibrous capsule and germinal center were
      observed in white-colored MFTs extending from the diaphragm to the heart. The
      number and size of the LCs were larger in 12-month-old mice than in 3-month-old
      mice in all of the examined strains. Moreover, B6 had an especially large number
      of LCs compared with DBA and MRL. The immune cells in the LCs consisted of mainly
      T-cells and some B-cells. The majority of T-cells were CD4+ helper T (Th) cells,
      rather than CD8+ cytotoxic T-cells and no obvious immune cell population
      difference was present among the strains. Furthermore, high endothelial venules
      and lymphatic vessels in the LCs were better developed in B6 mice than in the
      other strains. Interestingly, some CD133+ hematopoietic progenitor cells and some
      c-Kit+/CD127+ natural helper cells were detected in the LCs. BrdU+ proliferating
      cells were more abundant in the LCs of B6 mice than in the LCs of the other
      strains and the number of BrdU+ cells increased with age. This is the first
      report of LCs in mouse MFTs. We suggest that the mouse genetic background affects
      LC size and number. We term the LCs "mediastinal fat-associated lymphoid
      clusters". These clusters can be considered as niches for Th cell production. 

PMID- 24853671
TI  - Anoctamin 1 expression in the mouse auditory brainstem.
AB  - Calcium-activated chloride channels (CaCCs) are involved in numerous
      physiological functions, including the epithelial movement of fluid. Anoctamin 1
      (ANO1) has recently been cloned and characterized as a CaCC and is known to be
      expressed in various secretory epithelia and in nervous tissues such as the
      dorsal root ganglia and retina. However, data regarding the expression, function,
      and cellular and subcellular localization of CaCCs in the brain are still
      limited. We investigated the distribution and expression patterns of ANO1 in
      adult mouse brain. Reverse transcriptase plus the polymerase chain reaction,
      Western blot, and immunohistochemical analyses demonstrated that ANO1 was widely
      distributed throughout the brain. Furthermore, ANO1 was strongly expressed in two
      auditory brainstem nuclei: the medial nucleus of the trapezoid body (MNTB) and
      the anteroventral cochlear nucleus (AVCN). Double-labeling experiments revealed
      that this ANO1 expression was exclusive to the presynaptic endings of both the
      MNTB and AVCN. ANO1 is thus mainly localized at presynaptic terminals in various
      brain regions, specifically in two auditory brainstem nuclei, the MNTB and AVCN,
      and might therefore contribute to the high-frequency synaptic transmission of
      auditory signals. 

PMID- 24853672
TI  - Multi-lineage differentiation of human mesenchymal stromal cells on the
      biophysical microenvironment of cell-derived matrix.
AB  - We obtained fibroblast- (FDM) and preosteoblast- (PDM) derived matrices in vitro
      from their respective cells. Our hypothesis was that these naturally occurring
      cell-derived matrices (CDMs) would provide a better microenvironment for the
      multi-lineage differentiation of human mesenchymal stromal cells (hMSCs) than
      those based on traditional single-protein-based platforms. Cells cultured for 5-6
      days were decellularized with detergents and enzymes. The resulting matrices
      showed a fibrillar surface texture. Under osteogenic conditions, human bone
      marrow-derived stromal cells (HS-5) exhibited higher amounts of both mineralized
      nodule formation and alkaline phosphatase (ALP) expression than those cultured on
      plastic or gelatin. Osteogenic markers (Col I, osteopontin, and cbfa1) and ALP
      activity from cells cultured on PDM were notably upregulated at 4 weeks. The use
      of FDM significantly improved the cellular expression of chondrogenic markers
      (Sox 9 and Col II), while downregulating that of Col I at 4 weeks. Both CDMs were
      more effective in inducing cellular synthesis of glycosaminoglycan content than
      control substrates. We also investigated the effect of matrix surface texture on
      hMSC (PT-2501) differentiation; soluble matrix (S-matrix)-coated substrates
      exhibited a localized fibronectin (FN) alignment, whereas natural matrix (N
      matrix)-coated substrates preserved the naturally formed FN fibrillar alignment.
      hMSCs cultured for 4 weeks on N-matrices under osteogenic or chondrogenic
      conditions deposited a greater amount of calcium and proteoglycan than those
      cultured on S-matrices as assessed by von Kossa and Safranin O staining. In
      contrast to the expression levels of lineage-specific markers for cells cultured
      on gelatin, FN, or S-matrices, those cultured on N-matrices yielded highly
      upregulated levels. This study demonstrates not only the capacity of CDM for
      being an effective inductive template for the multi-lineage differentiation of
      hMSCs, but also the critical biophysical role that the matrix fibrillar texture
      itself plays on the induction of stem cell differentiation. 

PMID- 24853674
TI  - Comparison of pleural pressure measuring instruments.
AB  - OBJECTIVE: The objective of this study was to compare the accuracy of a handheld
      digital manometer (DM) and U-tube (UT) manometer with an electronic transducer
      (ET) manometer during thoracentesis. METHODS: Thirty-three consecutive patients
      undergoing thoracentesis were enrolled in the study. Pleural pressure (Ppl)
      measurements were made using a handheld DM (Compass; Mirador Biomedical), a UT
      water manometer, and an ET (reference instrument). End-expiratory Ppl was
      recorded after catheter insertion, after each aspiration of 240 mL, and prior to
      catheter removal. Volume of fluid removed, symptoms during thoracentesis, pleural
      elastance, and pleural fluid chemistry were also evaluated. RESULTS: A total of
      594 Ppl measurements were made in 30 patients during their thoracenteses. There
      was a strong linear correlation coefficient between elastance for the DM and ET
      (r = 0.9582, P < .001). Correlation was poor between the UT and ET (r = 0.0448, P
      = .84). Among the 15 patients who developed cough, recorded ET pressures ranged
      from -9 to +9 cm H2O at the time of symptom development, with a mean (SD) of 
      2.93 (4.89) cm H2O. ET and DM measurements among those patients with cough had a
      low correlation between these measurements (R2 = 0.104, P = .24). Nine patients
      developed chest discomfort and had ET pressures that ranged from -26 to +6 cm
      H2O, with a mean (SD) of -7.89 (9.97) cm H2O. CONCLUSIONS: The handheld DM
      provided a valid and easy-to-use method to measure Ppl during thoracentesis.
      Future studies are needed to investigate its usefulness in predicting clinically
      meaningful outcomes.

PMID- 24853673
TI  - Virus and autoantigen-specific CD4+ T cells are key effectors in a SCID mouse
      model of EBV-associated post-transplant lymphoproliferative disorders.
AB  - Polyclonal Epstein-Barr virus (EBV)-infected B cell line (lymphoblastoid cell
      lines; LCL)-stimulated T-cell preparations have been successfully used to treat
      EBV-positive post-transplant lymphoproliferative disorders (PTLD) in transplant
      recipients, but function and specificity of the CD4+ component are still poorly
      defined. Here, we assessed the tumor-protective potential of different CD4+ T
      cell specificities in a PTLD-SCID mouse model. Injection of different virus
      specific CD4+ T-cell clones showed that single specificities were capable of
      prolonging mouse survival and that the degree of tumor protection directly
      correlated with recognition of target cells in vitro. Surprisingly, some CD4+ T
      cell clones promoted tumor development, suggesting that besides antigen
      recognition, still elusive functional differences exist among virus-specific T
      cells. Of several EBV-specific CD4+ T-cell clones tested, those directed against
      virion antigens proved most tumor-protective. However, enriching these
      specificities in LCL-stimulated preparations conferred no additional survival
      benefit. Instead, CD4+ T cells specific for unknown, probably self-antigens were
      identified as principal antitumoral effectors in LCL-stimulated T-cell lines.
      These results indicate that virion and still unidentified cellular antigens are
      crucial targets of the CD4+ T-cell response in this preclinical PTLD-model and
      that enriching the corresponding T-cell specificities in therapeutic preparations
      may enhance their clinical efficacy. Moreover, the expression in several EBV
      negative B-cell lymphoma cell lines implies that these putative autoantigen(s)
      might also qualify as targets for T-cell-based immunotherapy of virus-negative B
      cell malignancies. 

PMID- 24853675
TI  - Evolution of pathogen specialisation in a host metapopulation: joint effects of
      host and pathogen dispersal.
AB  - Metapopulation processes are important determinants of epidemiological and
      evolutionary dynamics in host-pathogen systems, and are therefore central to
      explaining observed patterns of disease or genetic diversity. In particular, the
      spatial scale of interactions between pathogens and their hosts is of primary
      importance because migration rates of one species can affect both spatial and
      temporal heterogeneity of selection on the other. In this study we developed a
      stochastic and discrete time simulation model to specifically examine the joint
      effects of host and pathogen dispersal on the evolution of pathogen
      specialisation in a spatially explicit metapopulation. We consider a plant
      pathogen system in which the host metapopulation is composed of two plant
      genotypes. The pathogen is dispersed by air-borne spores on the host
      metapopulation. The pathogen population is characterised by a single life-history
      trait under selection, the infection efficacy. We found that restricted host
      dispersal can lead to high amount of pathogen diversity and that the extent of
      pathogen specialisation varied according to the spatial scale of host-pathogen
      dispersal. We also discuss the role of population asynchrony in determining
      pathogen evolutionary outcomes. 

PMID- 24853676
TI  - Cyclic lipodepsipeptides produced by Pseudomonas spp. naturally present in raw
      milk induce inhibitory effects on microbiological inhibitor assays for antibiotic
      residue screening.
AB  - Two Pseudomonas strains, identified as closely related to Pseudomonas tolaasii,
      were isolated from milk of a farm with frequent false-positive Delvotest results
      for screening putative antibiotic residues in raw milk executed as part of the
      regulatory quality programme. Growth at 5 to 7 degrees C of these isolates in
      milk resulted in high lipolysis and the production of bacterial inhibitors. The
      two main bacterial inhibitors have a molecular weight of 1168.7 and 1140.7 Da
      respectively, are heat-tolerant and inhibit Geobacillus stearothermophilus var.
      calidolactis, the test strain of most of the commercially available
      microbiological inhibitor tests for screening of antibiotic residues in milk.
      Furthermore, these bacterial inhibitors show antimicrobial activity against
      Staphylococcus aureus, Bacillus cereus and B. subtilis and also interfere
      negatively with yoghurt production. Following their isolation and purification
      with RP-HPLC, the inhibitors were identified by NMR analysis as cyclic
      lipodepsipeptides of the viscosin group. Our findings bring to light a new
      challenge for quality control in the dairy industry. By prolonging the
      refrigerated storage of raw milk, the keeping quality of milk is influenced by
      growth and metabolic activities of psychrotrophic bacteria such as pseudomonads.
      Besides an increased risk of possible spoilage of long shelf-life milk, the
      production at low temperature of natural bacterial inhibitors may also result in
      false-positive results for antibiotic residue screening tests based on microbial
      inhibitor assays thus leading to undue production loss. 

PMID- 24853677
TI  - Regulation of CBP and Tip60 coordinates histone acetylation at local and global
      levels during Ras-induced transformation.
AB  - Cell transformation is clearly linked to epigenetic changes. However, the role of
      the histone-modifying enzymes in this process is still poorly understood. In this
      study, we investigated the contribution of the histone acetyltransferase (HAT)
      enzymes to Ras-mediated transformation. Our results demonstrated that lysine
      acetyltransferase 5, also known as Tip60, facilitates histone acetylation of bulk
      chromatin in Ras-transformed cells. As a consequence, global H4 acetylation
      (H4K8ac and H4K12ac) increases in Ras-transformed cells, rendering a more
      decompacted chromatin than in parental cells. Furthermore, low levels of CREB
      binding protein (CBP) lead to hypoacetylation of retinoblastoma 1 (Rb1) and
      cyclin-dependent kinase inhibitor 1B (Cdkn1b or p27Kip1) tumour suppressor gene
      promoters to facilitate Ras-mediated transformation. In agreement with these
      data, overexpression of Cbp counteracts Ras transforming capability in a HAT
      dependent manner. Altogether our results indicate that CBP and Tip60 coordinate
      histone acetylation at both local and global levels to facilitate Ras-induced
      transformation. 

PMID- 24853680
TI  - Alemtuzumab and treatment of chronic lymphocytic leukemia and its immune-related
      disorders: one player on two tables.

PMID- 24853679
TI  - A new phylogeographic pattern of endemic Bufo bankorensis in Taiwan Island is
      attributed to the genetic variation of populations.
AB  - AIM: To comprehend the phylogeographic patterns of genetic variation in anurans
      at Taiwan Island, this study attempted to examine (1) the existence of various
      geological barriers (Central Mountain Ranges, CMRs); and (2) the genetic
      variation of Bufo bankorensis using mtDNA sequences among populations located in
      different regions of Taiwan, characterized by different climates and existing
      under extreme conditions when compared available sequences of related species B.
      gargarizans of mainland China. METHODOLOGY/PRINCIPAL FINDINGS: Phylogenetic
      analyses of the dataset with mitochondrial DNA (mtDNA) D-loop gene (348 bp)
      recovered a close relationship between B. bankorensis and B. gargarizans,
      identified three distinct lineages. Furthermore, the network of mtDNA D-loop gene
      (564 bp) amplified (279 individuals, 27 localities) from Taiwan Island indicated
      three divergent clades within B. bankorensis (Clade W, E and S), corresponding to
      the geography, thereby verifying the importance of the CMRs and Kaoping River
      drainage as major biogeographic barriers. Mismatch distribution analysis,
      neutrality tests and Bayesian skyline plots revealed that a significant
      population expansion occurred for the total population and Clade W, with horizons
      dated to approximately 0.08 and 0.07 Mya, respectively. These results suggest
      that the population expansion of Taiwan Island species B. bankorensis might have
      resulted from the release of available habitat in post-glacial periods, the
      genetic variation on mtDNA showing habitat selection, subsequent population
      dispersal, and co-distribution among clades. CONCLUSIONS: The multiple origins
      (different clades) of B. bankorensis mtDNA sequences were first evident in this
      study. The divergent genetic clades found within B. bankorensis could be
      independent colonization by previously diverged lineages; inferring B.
      bankorensis originated from B. gargarizans of mainland China, then dispersal
      followed by isolation within Taiwan Island. Highly divergent clades between W and
      E of B. bankorensis, implies that the CMRs serve as a genetic barrier and
      separated the whole island into the western and eastern phylogroups.

PMID- 24853681
TI  - Inflammaging in skin and other tissues - the roles of complement system and
      macrophage.
AB  - Inflammaging refers to a continuous, low-grade inflammation associated with
      aging. Such chronic inflammatory response could build up with time and gradually
      causes tissue damage. It is considered as one of the driving forces for many age
      related diseases such as diabetes, atherosclerosis, age-related macular
      degeneration (AMD), and skin aging. There is mounting evidence that indicates
      aging is driven by the pro-inflammatory cytokines and substances produced by our
      body's innate immune system. The macrophage and complement system, two important
      components of innate immune system, have attracted more and more attention since
      they appear to be involved in the pathogenesis of several inflammaging-associated
      diseases, such as AMD and atherosclerosis. This paper will review what we know
      about these two innate immune systems in the pathogenesis of AMD, atherosclerosis
      and skin aging.

PMID- 24853683
TI  - The effect of cannabidiol on ischemia/reperfusion-induced ventricular
      arrhythmias: the role of adenosine A1 receptors.
AB  - Cannabidiol (CBD) is a nonpsychoactive phytocannabinoid with anti-inflammatory
      activity mediated by enhancing adenosine signaling. As the adenosine A1 receptor
      activation confers protection against ischemia/reperfusion (I/R)-induced
      ventricular arrhythmias, we hypothesized that CBD may have antiarrhythmic effect
      through the activation of adenosine A1 receptor. Cannabidiol has recently been
      shown to suppress ischemia-induced ventricular arrhythmias. We aimed to research
      the effect of CBD on the incidence and the duration of I/R-induced ventricular
      arrhythmias and to investigate the role of adenosine A1 receptor activation in
      the possible antiarrhythmic effect of CBD. Myocardial ischemia and reperfusion
      was induced in anesthetized male rats by ligating the left anterior descending
      coronary artery for 6 minutes and by loosening the bond at the coronary artery,
      respectively. Cannabidiol alone was given in a dose of 50 ug/kg, 10 minutes prior
      to coronary artery occlusion and coadministrated with adenosine A1 receptor
      antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) in a dose of 100 ug/kg, 15
      minutes prior to coronary artery occlusion to investigate whether the
      antiarrhythmic effect of CBD is modified by the activation of adenosine A1
      receptors. The experimental groups were as follows: (1) vehicle control (n = 10),
      (2) CBD (n = 9), (3) DPCPX (n = 7), and (4) CBD + DPCPX group (n = 7).
      Cannabidiol treatment significantly decreased the incidence and the duration of
      ventricular tachycardia, total length of arrhythmias, and the arrhythmia scores
      compared to control during the reperfusion period. The DPCPX treatment alone did
      not affect the incidence and the duration of any type of arrhythmias. However,
      DPCPX aborted the antiarrhythmic effect of CBD when it was combined with it. The
      present results demonstrated that CBD has an antiarrhythmic effect against I/R
      induced arrhythmias, and the antiarrhythmic effect of CBD may be mediated through
      the activation of adenosine A1 receptor. 

PMID- 24853686
TI  - A case of two commentaries.

PMID- 24853684
TI  - Benznidazole biotransformation and multiple targets in Trypanosoma cruzi revealed
      by metabolomics.
AB  - BACKGROUND: The first line treatment for Chagas disease, a neglected tropical
      disease caused by the protozoan parasite Trypanosoma cruzi, involves
      administration of benznidazole (Bzn). Bzn is a 2-nitroimidazole pro-drug which
      requires nitroreduction to become active, although its mode of action is not
      fully understood. In the present work we used a non-targeted MS-based
      metabolomics approach to study the metabolic response of T. cruzi to Bzn.
      METHODOLOGY/PRINCIPAL FINDINGS: Parasites treated with Bzn were minimally altered
      compared to untreated trypanosomes, although the redox active thiols
      trypanothione, homotrypanothione and cysteine were significantly diminished in
      abundance post-treatment. In addition, multiple Bzn-derived metabolites were
      detected after treatment. These metabolites included reduction products,
      fragments and covalent adducts of reduced Bzn linked to each of the major low
      molecular weight thiols: trypanothione, glutathione, gamma-glutamylcysteine,
      glutathionylspermidine, cysteine and ovothiol A. Bzn products known to be
      generated in vitro by the unusual trypanosomal nitroreductase, TcNTRI, were found
      within the parasites, but low molecular weight adducts of glyoxal, a proposed
      toxic end-product of NTRI Bzn metabolism, were not detected.
      CONCLUSIONS/SIGNIFICANCE: Our data is indicative of a major role of the thiol
      binding capacity of Bzn reduction products in the mechanism of Bzn toxicity
      against T. cruzi.

PMID- 24853682
TI  - Brain-skin connection: stress, inflammation and skin aging.
AB  - The intricate relationship between stress and skin conditions has been documented
      since ancient times. Recent clinical observations also link psychological stress
      to the onset or aggravation of multiple skin diseases. However, the exact
      underlying mechanisms have only been studied and partially revealed in the past
      20 years or so. In this review, the authors will discuss the recent discoveries
      in the field of "Brain-Skin Connection", summarizing findings from the
      overlapping fields of psychology, endocrinology, skin neurobiology, skin
      inflammation, immunology, and pharmacology. 

PMID- 24853685
TI  - Immunoglobulin G expression in lung cancer and its effects on metastasis.
AB  - Lung cancer is one of the leading malignancies worldwide, but the regulatory
      mechanism of its growth and metastasis is still poorly understood. We
      investigated the possible expression of immunoglobulin G (IgG) genes in squamous
      cell carcinomas and adenocarcinomas of the lung and related cancer cell lines.
      Abundant mRNA of IgG and essential enzymes for IgG synthesis, recombination
      activation genes 1, 2 (RAG1, 2) and activation-induced cytidine deaminase (AID)
      were detected in the cancer cells but not in adjacent normal lung tissue or
      normal lung epithelial cell line. The extents of IgG expression in 86 lung
      cancers were found to associate with clinical stage, pathological grade and lymph
      node metastasis. We found that knockdown of IgG with siRNA resulted in decreases
      of cellular proliferation, migration and attachment for cultured lung cancer
      cells. Metastasis-associated gene 1 (MTA1) appeared to be co-expressed with IgG
      in lung cancer cells. Statistical analysis showed that the rate of IgG expression
      was significantly correlated to that of MTA1 and to lymph node metastases.
      Inhibition of MTA1 gene expression with siRNA also led to decreases of cellular
      migration and attachment for cultured lung cancer cells. These evidences
      suggested that inhibition of cancer migration and attachment induced by IgG down
      regulation might be achieved through MTA1 regulatory pathway. Our findings
      suggest that lung cancer-produced IgG is likely to play an important role in
      cancer growth and metastasis with significant clinical implications. 

PMID- 24853687
TI  - Pars plana vitrectomy compared with pars plana vitrectomy combined with scleral
      buckle in the primary management of noncomplex rhegmatogenous retinal detachment.
AB  - PURPOSE: To compare pars plana vitrectomy (PPV) with PPV combined with scleral
      buckle (PPV/SB) in the treatment of primary, noncomplex rhegmatogenous retinal
      detachment in an academic setting. METHODS: Retrospective review of 74
      consecutive cases that underwent either PPV or PPV/SB for primary rhegmatogenous
      retinal detachment at New York Presbyterian Hospital, Weill Cornell Medical
      College. Fifty-two eyes underwent PPV alone while 22 eyes had PPV combined with
      SB. All eyes had a minimum of 2 months of follow-up. The main outcome measure was
      single surgery anatomical success. RESULTS: Patients in the PPV/SB group were
      less likely to be phakic (P = 0.05) and more likely to have an inferior retinal
      break (P = 0.001) when compared with the PPV group. Between groups, there was no
      difference in eyes with peripheral retinal lattice degeneration (P = 0.929),
      multiple breaks (P = 0.801), breaks seen preoperatively (P = 0.095), or those
      presenting with the macula off retinal detachment (P = 0.548). The majority of
      patients in both groups underwent small-gauge surgery (23 G or 25 G) (P = 0.65).
      Attachment of the retina was obtained in 100% of the patients in both groups at
      most recent follow-up. Single surgery anatomical success was similar between
      groups (83% PPV vs. 86% PPV/SB; P = 0.695). Mean best-corrected Snellen visual
      acuity improved in both groups (P = 0.75), with a final best-corrected Snellen
      visual acuity of 0.418 logMAR in the PPV group and 0.479 logMAR in the PPV/SB
      group (P = 0.61). When comparing PPV with PPV/SB, no difference in single surgery
      anatomical success existed after evaluating eyes with inferior breaks (P = 0.68),
      pseudophakia (P = 0.75), or when small-gauge surgery was performed (P = 0.76).
      CONCLUSION: We did not find significant differences in single surgery anatomical
      success, final anatomical success, or change in visual acuity when comparing PPV
      with PPV/SB in the repair of primary noncomplex rhegmatogenous retinal detachment
      in an academic setting where vitreoretinal fellows participate in key aspects of
      all cases.

PMID- 24853688
TI  - Choroidal thickness changes after diabetes type 2 and blood pressure control in a
      hospitalized situation.
AB  - PURPOSE: To investigate the effect of acute diabetic control on choroidal
      thickness in patients with Type 2 diabetes. METHODS: Seventeen eyes of 17
      patients with Type 2 diabetes were included in this prospective observational
      study. The patients with Type 2 diabetes who were scheduled to undergo a program
      of intensive diabetic control underwent prototype high-penetration optical
      coherence tomography before and 2 weeks after the start of treatment. The
      choroidal thickness changes 2 weeks after the protocol of intensive diabetic
      control were assessed, and associated ophthalmologic and general parameters were
      explored. Seventeen eyes of 17 healthy volunteers were included to compare
      diabetic patients. The choroidal thickness also was measured in this group at
      baseline and after 2 weeks. And the intraobserver and interobserver
      reproducibility were verified using this control group. RESULTS: The
      intraobserver (intraclass coefficient, 0.992) and interobserver reproducibility
      (0.982) in our subfoveal choroidal thickness measurement were high. The mean
      subfoveal choroidal thickness after 2 weeks (226 +/- 56 MUm) was significantly
      greater than at baseline (215 +/- 52 MUm, P < 0.05); there was no difference
      between the baseline and 2-week values in the control group (baseline, 312 +/-
      113 vs. 2-week value, 307 +/- 103 MUm; P = 0.17). The changes in refractive error
      (P < 0.001), axial length (P < 0.01), and diastolic blood pressure (P < 0.01)
      were associated significantly with changes in choroidal thickness 2 weeks after
      the intensive control. The pretreatment body mass index (P < 0.05) and hemoglobin
      A1c (P < 0.005) also were associated significantly with increased choroidal
      thickness. CONCLUSION: Diabetic patients showed a significant increase of
      choroidal thickness after the intensive control. Various ophthalmologic and
      systemic parameters seem to affect the choroidal thickness changes. This may be
      related to the progression of retinopathy after acute glycemic control.

PMID- 24853689
TI  - Floral development in Scutellaria pinnatifida (Lamiaceae): the ontogenetic basis
      for sepal reduction.
AB  - The Scutellaria is a Labiatae genus (subfamily Scutellarioideae) with a highly
      specialised floral structure. The genus is characterised by a peculiar two-lobed
      calyx with a projecting appendage, named the scutellum. Here, we present a
      detailed analysis of floral development, using epi-illumination light microscopy,
      to clarify open questions about its floral organisation. Floral whorls appeared
      in an acropetal sequence, with a marked temporal overlap of petal and stamen
      appearance. Organ appearance in each whorl proceeded unidirectionally from the
      abaxial to the adaxial side. Significant developmental features included the
      formation of the scutellum, reduction of sepal lobes and formation of a three
      lobed nectary disc. Our study revealed that both loss of organ initiation and
      fusion of primordia are responsible for the reduction in sepal members in
      Scutellaria. The nectary structure was markedly different from most other studied
      Lamiaceae. 

PMID- 24853690
TI  - Role of CA2+/calmodulin on ethanol neurobehavioral effects.
AB  - RATIONALE: The cAMP-dependent protein kinase A (PKA) signaling transduction
      pathway has been shown to play an important role in the modulation of several
      ethanol-induced behaviors. Different studies have demonstrated intracellular
      calcium (Ca(2+))-dependent activation of the PKA cascade after ethanol
      administration. Thus, the cAMP cascade mediator Ca(2+)-dependent calmodulin (CaM)
      has been strongly implicated in the central effects of ethanol. OBJECTIVES: In
      this study, we assessed the role of the CaM inhibitor W7 on ethanol-induced
      stimulation, ethanol intake, and ethanol-induced activation of PKA. METHODS:
      Swiss mice were pretreated with W7 (0-10 mg/kg) 30 min before ethanol (0-3.75
      g/kg) administration. Immediately, animals were placed during 20 min in an open
      field chamber. Ethanol (10 %, v/v) intake in 2 h was assessed using a limited
      access paradigm. Experiments with caffeine (0-15 mg/kg), cocaine (0-4 mg/kg), and
      saccharine (0.1 %, w/v) were designed to compare their results to those obtained
      with ethanol. Western blot was assayed 45 min after ethanol administration.
      RESULTS: Results showed that pretreatment with W7, reduced selectively in a dose
      dependent fashion ethanol-induced locomotor stimulation and ethanol intake. The
      ethanol-induced activation of PKA was also prevented by W7 administration.
      CONCLUSIONS: These results demonstrate that CaM inhibition resulted in a
      selective reduction of ethanol-stimulating effects and ethanol intake. The PKA
      activation induced by ethanol was blocked after the CaM blockade with W7. These
      results provide further evidence of the key role of cellular Ca(2+)-dependent
      pathways on the central effects of ethanol.

PMID- 24853691
TI  - Declining childhood and adolescent cancer mortality.
AB  - BACKGROUND: To evaluate whether progress continues in identifying more effective
      treatments for children and adolescents with cancer, the authors examined both
      overall and disease-specific childhood cancer mortality rates for the United
      States, focusing on data from 2000 to 2010. METHODS: Age-adjusted US mortality
      trends from 1975 to 2010 were estimated using joinpoint regression analysis.
      Analyses of annual percentage change (APC) were performed on the same diagnostic
      groupings for the period restricted to 2000 through 2010 for groupings ages <20
      years, <15 years, and 15 to 19 years. RESULTS: After a plateau in mortality rates
      during 1998 to 2002 (APC, 0.3%), the annual decline in childhood cancer mortality
      from 2002 to 2010 (APC, -2.4%) was similar to that observed from 1975 to 1998
      (APC, -2.7%). Statistically significant declines in mortality rates from 2000 to
      2010 were noted for acute lymphoblastic leukemia, acute myeloid leukemia, non
      Hodgkin lymphoma, Hodgkin lymphoma, neuroblastoma, central nervous system
      cancers, and gonadal cancers. From 2000 to 2010, the rates of decline in
      mortality for the group ages 15 to 19 years generally were equal to or greater
      than the rates of decline for the group ages birth to 14 years. Improvements in
      treatment since 1975 resulted >45,000 cancer deaths averted through 2010.
      CONCLUSIONS: Cancer mortality for both children and adolescents declined from
      2000 to 2010, with significant declines observed for multiple cancer types.
      However, greater than 1900 cancer deaths still occur each year among children and
      adolescents in the United States, and many survivors experience long-term effects
      that limit their quality of life. Continued research directed toward identifying
      more effective treatments that produce fewer long-term sequelae is critical to
      address these remaining challenges.

PMID- 24853692
TI  - The 'active ingredients' for successful community engagement with disadvantaged
      expectant and new mothers: a qualitative comparative analysis.
AB  - AIMS: To explore which conditions of community engagement are implicated in
      effective interventions targeting disadvantaged pregnant women and new mothers.
      BACKGROUND: Adaptive experiences during pregnancy and the early years are key to
      reducing health inequalities in women and children worldwide. Public health
      nurses, health visitors and community midwives are well placed to address such
      disadvantage, often using community engagement strategies. Such interventions are
      complex; however, and we need to better understand which aspects of community
      engagement are aligned with effectiveness. DESIGN: Qualitative comparative
      analysis conducted in 2013, of trials data included in a recently published
      systematic review. METHODS: Two reviewers agreed on relevant conditions from 24
      maternity or early years intervention studies examining four models of community
      engagement. Effect size estimates were converted into 'fuzzy' effectiveness
      categories and truth tables were constructed. Using fsQCA software, Boolean
      minimization identified solution sets. Random effects multiple regression and
      fsQCA were conducted to rule out risk of methodological bias. RESULTS/FINDINGS:
      Studies focused on antenatal, immunization, breastfeeding and early professional
      intervention outcomes. Peer delivery (consistency 0.83; unique coverage 0.63);
      and mother-professional collaboration (consistency 0.833; unique coverage 0.21)
      were moderately aligned with effective interventions. Community-identified health
      need plus consultation/collaboration in intervention design and leading on
      delivery were weakly aligned with 'not effective' interventions (consistency
      0.78; unique coverage 0.29). CONCLUSIONS: For disadvantaged new and expectant
      mothers, peer or collaborative delivery models could be used in interventions. A
      need exists to design and test community engagement interventions in other areas
      of maternity and early years care and to further evaluate models of empowerment.

PMID- 24853693
TI  - Single rib metastasis of follicular thyroid cancer.

PMID- 24853694
TI  - A survey of the practice patterns of gynecologic oncologists dealing with
      hereditary cancer patients in Japan.
AB  - Hereditary breast and ovarian cancer syndrome (HBOC) is a significant type of
      familial ovarian cancer. A survey of gynecologic oncologists was conducted in
      order to characterize the state of care and awareness of information provision
      for HBOC in Japan and to identify information necessary to enhance HBOC care. All
      gynecologic oncologists certified by the Japan Society of Gynecologic Oncology
      (JSGO) as specialists in the treatment of ovarian cancer were included. They were
      sent a 44-question questionnaire dealing with the background of the respondent,
      the facilities at the respondent's medical institution, how the family history
      interview is conducted, awareness of and practice behavior toward HBOC,
      performance of genetic testing, and performance of risk-reducing salpingo
      oophorectomy (RRSO). The response rate was 50.1 %. About 60 % of respondents
      stated that "I administer care with HBOC in mind" and "I want to be involved in
      the care of HBOC." However, only 2 in 3 doctors was able to explain HBOC to
      patients, fewer than 1 in 5 doctors was able to give counseling to patients, 1 in
      10 doctors provided printed information to patients suspected of having a
      hereditary cancer, and 1 in 7 doctors recommended that patients suspected of
      having a hereditary cancer visit the department of genetics. The provision of
      information to patients, recommending that patients visit the department of
      genetics, and the performance of genetic testing were dependent on whether a
      department of genetics was present in the respondent's institution. The survey
      also found that RRSO is not widely performed in Japan. 

PMID- 24853696
TI  - Human Infrapatellar Fat Pad-Derived Stromal Cells Have More Potent
      Differentiation Capacity Than Other Mesenchymal Cells and Can Be Enhanced by
      Hyaluronan.
AB  - The microenvironment plays an important role in the homing in and differentiation
      of stem cells to repair injured tissue. Infrapatellar fat pad stromal cells
      (IFPSCs) are a promising source of such cells for the repair of articular injury
      induced degeneration. This study investigated the chemotaxis of IFPSCs to
      chondrocytes and the effect of hyaluronan (HA) on the biological and regenerative
      properties of IFPSCs. The IFPSCs were obtained from patients undergoing
      arthroscopy and cultured via a standard 2-week culture protocol that yielded more
      than 10 million cells on passage 3. The results showed that the IFPSCs had a
      higher capacity for chondrogenic differentiation than mesenchymal cells from body
      fat, bone marrow, and Wharton's jelly of the umbilical cord. The IFPSCs cultured
      on 25% or 50% HA showed better osteogenic and adipogenic capabilities than those
      without HA or with 75% HA (p < 0.001). Cultures of the IFPSCs on 25% HA had a
      fourfold increase in chondrogenic differentiation compared to cultures without
      HA, which was better than with 50% and 75% HA (p < 0.05). Cell proliferation was
      not affected by the presence of HA. In conclusion, IFPSCs have a strong potential
      for chondrogenic regeneration, which can even be augmented in a 25% HA
      microenvironment. 

PMID- 24853695
TI  - Rapid and cost effective screening of breast and ovarian cancer genes using novel
      sequence capture method in clinical samples.
AB  - BRCA1 and BRCA2 are two well-known genes in the background of hereditary breast
      and ovarian cancer. There is also evidence that several other genes play an
      important role in the pathogenesis of these two malignancies. Latest population
      scaled studies showed that certain mutations in different genes could cause
      similar risk elevation like BRCA2 mutations. In this study we present a new
      method to analyse the risk assessment of women to breast and ovarian cancer.
      Using Haloplex, a novel sequence capture method combined with next-generation
      sequencing we were able to perform rapid and cost-effective screening of 16 genes
      that could be associated with an increased risk of breast and ovarian cancer. The
      rapid and cost effective analysis of this 16-gene cohort can reveal the genetic
      background of approximately 30 % of hereditary and familiar cases of breast and
      ovarian cancers. Thus, it opens up a new and high-throughput approach with fast
      turnaround time to the genetic diagnostics of these disorders and may be helpful
      to investigate other familial genetic disorders as well.

PMID- 24853697
TI  - Changes in daily occupations and the meaning of work for three women caring for
      relatives post-stroke.
AB  - STUDY AIM: This qualitative study explored how some working Austrians experienced
      and coped with changes in their daily occupations after becoming informal carers
      of persons who had had a stroke. The study provides insights into the working
      carers' occupational experiences and strategies during a period of pronounced
      life changes. METHODS: Three participants, who were employed in full- or part
      time work, as well as being informal carers of persons who had had a stroke, were
      interviewed on two occasions. The data from these interviews were analysed using
      Interpretative Phenomenological Analyses. RESULTS: Carers found themselves in an
      ongoing process, ranging from the disruption of daily occupations to their
      eventual restructure. First, the stroke led to involuntary changes in the carers'
      daily life, which resulted in challenges in their own, and in shared,
      occupations. Second, carers actively changed their values and performance of
      occupations, which appeared to be a strategy to shape their well-being. Paid work
      was found to be a stabilizing and balancing occupation, which contributed to
      coping and the well-being of carers. CONCLUSIONS: The authors' findings
      demonstrate the benefits of paid work and engagement in meaningful occupation for
      the carers' well-being. These results should encourage occupational therapists to
      be sensitive to the complexity of the lives of working informal carers.

PMID- 24853698
TI  - BVA poses questions about the impact of Scottish independence.

PMID- 24853699
TI  - Halal labelling 'won't help animal welfare', says BVA.

PMID- 24853700
TI  - Dangerous dog owners face tougher penalties.

PMID- 24853701
TI  - Veterinary academic receives honorary OBE.

PMID- 24853702
TI  - Researchers draw attention to 'toxic shock-like' infection in dogs.

PMID- 24853703
TI  - Tackling emerging and re-emerging livestock diseases in Europe.

PMID- 24853704
TI  - Plans to increase transparency on animal use in research.

PMID- 24853705
TI  - Celebrating vet practices and staff.

PMID- 24853706
TI  - Northern Ireland disease surveillance report for January to March 2014.
AB  - Listerial encephalitis in adult cattle Oxalate nephrosis in Zwartble ewes and
      lambs Histomonosis in chickens Feline tuberculosis caused by Mycobacterium bovis
      These are among matters discussed in the Northern Ireland animal disease
      surveillance quarterly report for January to March 2014. 

PMID- 24853707
TI  - Control of scrapie by selective breeding: what are we getting for free?

PMID- 24853708
TI  - Testing for exclusion of notifiable avian disease.

PMID- 24853709
TI  - Bovine TB controls.

PMID- 24853710
TI  - Restructuring the RCVS fellowship.

PMID- 24853711
TI  - Regular physical activity reduces the effects of Achilles tendon vibration on
      postural control for older women.
AB  - The aim was to determine in what extent physical activity influences postural
      control when visual, vestibular, and/or proprioceptive systems are disrupted. Two
      groups of healthy older women: an active group (74.0 +/- 3.8 years) who practiced
      physical activities and a sedentary group (74.7 +/- 6.3 years) who did not,
      underwent 12 postural conditions consisted in altering information emanating from
      sensory systems by means of sensory manipulations (i.e., eyes closed, cervical
      collar, tendon vibration, electromyostimulation, galvanic vestibular stimulation,
      foam surface). The center of foot pressure velocity was recorded on a force
      platform. Results indicate that the sensory manipulations altered postural
      control. The sedentary group was more disturbed than the active group by the use
      of tendon vibration. There was no clear difference between the two groups in the
      other conditions. This study suggests that the practice of physical activities is
      beneficial as a means of limiting the effects of tendon vibration on postural
      control through a better use of the not manipulated sensory systems and/or a more
      efficient reweighting to proprioceptive information from regions unaffected by
      the tendon vibration.

PMID- 24853712
TI  - Capsaicin and dihydrocapsaicin determination in chili pepper genotypes using
      ultra-fast liquid chromatography.
AB  - Research was carried out to estimate the levels of capsaicin and dihydrocapsaicin
      that may be found in some heat tolerant chili pepper genotypes and to determine
      the degree of pungency as well as percentage capsaicin content of each of the
      analyzed peppers. A sensitive, precise, and specific ultra fast liquid
      chromatographic (UFLC) system was used for the separation, identification and
      quantitation of the capsaicinoids and the extraction solvent was acetonitrile.
      The method validation parameters, including linearity, precision, accuracy and
      recovery, yielded good results. Thus, the limit of detection was 0.045 ug/kg and
      0.151 ug/kg for capsaicin and dihydrocapsaicin, respectively, whereas the limit
      of quantitation was 0.11 ug/kg and 0.368 ug/kg for capsaicin and
      dihydrocapsaicin. The calibration graph was linear from 0.05 to 0.50 ug/g for
      UFLC analysis. The inter- and intra-day precisions (relative standard deviation)
      were <5.0% for capsaicin and <9.9% for dihydrocapsaicin while the average
      recoveries obtained were quantitative (89.4%-90.1% for capsaicin, 92.4%-95.2% for
      dihydrocapsaicin), indicating good accuracy of the UFLC method. AVPP0705,
      AVPP0506, AVPP0104, AVPP0002, C05573 and AVPP0805 showed the highest
      concentration of capsaicin (12,776, 5,828, 4,393, 4,760, 3,764 and 4,120 ug/kg)
      and the highest pungency level, whereas AVPP9703, AVPP0512, AVPP0307, AVPP0803
      and AVPP0102 recorded no detection of capsaicin and hence were non-pungent. All
      chili peppers studied except AVPP9703, AVPP0512, AVPP0307, AVPP0803 and AVPP0102
      could serve as potential sources of capsaicin. On the other hand, only genotypes
      AVPP0506, AVPP0104, AVPP0002, C05573 and AVPP0805 gave a % capsaicin content that
      falls within the pungency limit that could make them recommendable as potential
      sources of capsaicin for the pharmaceutical industry. 

PMID- 24853713
TI  - Seasonal variation and resin composition in the Andean tree Austrocedrus
      chilensis.
AB  - Little is known about the changes in resin composition in South American
      gymnosperms associated with the different seasons of the year. The diterpene
      composition of 44 resin samples from seven Austrocedrus chilensis (Cupressaceae)
      trees, including male and female individuals, was investigated in three different
      seasons of the year (February, June and November). Twelve main diterpenes were
      isolated by chromatographic means and identified by gas chromatography-mass
      spectrometry and nuclear magnetic resonance (NMR). The diterpene composition was
      submitted to multivariate analysis to find possible associations between chemical
      composition and season of the year. The principal component analysis showed a
      clear relation between diterpene composition and season. The most characteristic
      compounds in resins collected in summer were Z-communic acid (9) and 12-oxo-labda
      8(17),13E-dien-19 oic acid methyl ester (10) for male trees and 8(17),12,14
      labdatriene (7) for female trees. For the winter samples, a clear correlation of
      female trees with torulosic acid (6) was observed. In spring, E-communic acid (8)
      and Z-communic acid (9) were correlated with female trees and 18-hydroxy isopimar
      15-ene (1) with male tree resin. A comparison between percent diterpene
      composition and collection time showed p < 0.05 for isopimara-8(9),15-diene (2),
      sandaracopimaric acid (4), compound (7) and ferruginol (11). 

PMID- 24853714
TI  - Evaluation of antioxidant activity, polyphenolic compounds, amino acids and
      mineral elements of representative genotypes of Lonicera edulis.
AB  - The aim of this study was to evaluate the bioactive substances in 19 berry
      cultivars of edible honeysuckle (Lonicera edulis). A statistical evaluation was
      used to determine the relationship between the content of selected bioactive
      substances and individual cultivars. Regarding mineral elements, the content of
      sodium was measured using potentiometry and spectrophotometry. The content of
      selected polyphenolic compounds with high antioxidant activity was determined by
      a HPLC-UV/ED method. The total amount of polyphenols was determined by the Folin
      Ciocalteu method. The antioxidant activity was determined using five methods
      (DPPH, FRAP, ABTS, FR and DMPD) that differ in their principles. The content of
      13 amino acids was determined by ion-exchange chromatography. The experimental
      results obtained for the different cultivars were evaluated and compared by
      statistical and bioinformatic methods. A unique feature of this study lies in the
      exhaustive analysis of the chosen parameters (amino acids, mineral elements,
      polyphenolic compounds and antioxidant activity) during one growing season. 

PMID- 24853715
TI  - A simple hydrophilic palladium(II) complex as a highly efficient catalyst for
      room temperature aerobic Suzuki coupling reactions in aqueous media.
AB  - A study on room temperature Suzuki cross-coupling in an aqueous medium was
      carried out using a simple hydrophilic palladium (II) complex, trans
      PdCl2(NH2CH2COOH)2 as catalyst in the presence of K2CO3 in air. This approach
      with a comparatively inexpensive and hydrophilic catalyst, mild reaction
      condition and aqueous media exhibits excellent catalytic activity towards the
      Suzuki coupling of aryl bromides and arylboronic acids, and good yields were
      obtained in the Suzuki coupling of activated aryl chlorides. 

PMID- 24853716
TI  - Ruthenium tetroxide and perruthenate chemistry. Recent advances and related
      transformations mediated by other transition metal oxo-species.
AB  - In the last years ruthenium tetroxide is increasingly being used in organic
      synthesis. Thanks to the fine tuning of the reaction conditions, including pH
      control of the medium and the use of a wider range of co-oxidants, this species
      has proven to be a reagent able to catalyse useful synthetic transformations
      which are either a valuable alternative to established methods or even, in some
      cases, the method of choice. Protocols for oxidation of hydrocarbons, oxidative
      cleavage of C-C double bonds, even stopping the process at the aldehyde stage,
      oxidative cleavage of terminal and internal alkynes, oxidation of alcohols to
      carboxylic acids, dihydroxylation of alkenes, oxidative degradation of phenyl and
      other heteroaromatic nuclei, oxidative cyclization of dienes, have now reached a
      good level of improvement and are more and more included into complex synthetic
      sequences. The perruthenate ion is a ruthenium (VII) oxo-species. Since its
      introduction in the mid-eighties, tetrapropylammonium perruthenate (TPAP) has
      reached a great popularity among organic chemists and it is mostly employed in
      catalytic amounts in conjunction with N-methylmorpholine N-oxide (NMO) for the
      mild oxidation of primary and secondary alcohols to carbonyl compounds. Its use
      in the oxidation of other functionalities is known and recently, its utility in
      new synthetic transformations has been demonstrated. New processes, synthetic
      applications, theoretical studies and unusual transformations, published in the
      last eight years (2006-2013), in the chemistry of these two oxo-species, will be
      covered in this review with the aim of offering a clear picture of their
      reactivity. When appropriate, related oxidative transformations mediated by other
      metal oxo-species will be presented to highlight similarities and differences. An
      historical overview of some aspects of the ruthenium tetroxide chemistry will be
      presented as well. 

PMID- 24853717
TI  - The adhesion and growth of both the human primary gingival epithelial cells and
      Streptococcus mutans on micro-arc oxidized titanium.
AB  - With good osseointegration properties, micro-arc oxidation has now gradually
      become the key point in basic research and clinical trials, but interface between
      the implant surface treated by micro-arc oxidation and gingival soft tissues has
      been seldom reported. The influences of micro-arc oxidation surface treatment on
      the biological behavior of primary human gingival epithelial cells (hGEC) and
      common pathogen Streptococcus mutans have been studied. MTT method was taken to
      test the adhesion and growth of hGEC on different treated surfaces. No
      significant changes were found between with or without MAO- treated surface.
      However, higher growth rate was observed in MAO group at first and third days,
      although it showed no significant difference at fifth and seventh day. Secretions
      of EGF of the cells grown on both surfaces were also no big changes (P > 0.05).
      RT-PCR showed adhesion gene of hGEC, E-cad on the first day of micro-arc
      oxidation surface treatment, expression level is higher than that of polishing
      group (P < 0.05), but no significant difference of the expression levels of
      Itgbeta1, PCNA, and EGF. Finally, easier adhesion and high growth rate of
      Streptococcus mutans were found at MAO-treated surface (P < 0.05). In conclusion,
      our data suggested MAO-treated Ti surface may favor epithelial cell adhesion, but
      it also increase the risk of bacterial infection.

PMID- 24853718
TI  - Calcitonin gene-related peptide inhibits osteolytic factors induced by osteoblast
      in co-culture system with breast cancer.
AB  - Recently, it was found that alpha-Calcitonin gene-related peptide (CGRP) was
      associated with breast cancer metastases, but the role of CGRP in interaction
      between breast cancer and osteoblast during bone metastases is not clear. Here,
      we investigated the effect of CGRP on osteoblast in co-culture system with breast
      cancer. Using a breast cancer-osteoblast co-culture system, we chose MDA-MB-231
      for breast cancer and human cell line MG-63 for osteoblast. CGRP was added to
      this co-culture system. The expression levels of the Runx2, RANK1, and
      osteoprotegerin (OPG) were analyzed using real-time PCR and western blot. CGRP
      receptors were investigated by immunofluorescence. We found that breast cancer
      cells cause osteolysis lesions by upregulating Runx2 expression, decreasing OPG
      expression, and increasing RANKL expression in osteoblasts. Our data prove that
      CGRP can regulate osteoclast coupling genes in osteoblast by increasing OPG, and
      decreasing RANKL and Runx2 expressions in a time-dependent manner; and inhibit
      those osteolytic factors induced by interaction between breast cancer cells and
      osteoblast. This inhibition could be abolished by the CGRP antagonist, CGRP8-37.
      In conclusion, calcitonin receptor-like receptor is the key player for CGRP's
      effect in this co-culture system. 

PMID- 24853719
TI  - Electrophysiological follow-up of patients with chronic peripheral neuropathy
      induced by occupational intoxication with n-hexane.
AB  - The aim of this study is to characterize and dynamically monitor the progress of
      peripheral neuropathy induced by n-hexane by electromyography and nerve
      conduction velocity (NCV-EMG). Twenty-five patients with n-hexane poisoning from
      an electronic company were investigated in the year 2009. The occupational
      history of these workers was collected, and toxic substance exposure was
      identified. Neurologic inspection and regular NCV-EMG inspection were performed
      for all patients upon hospital admission and after 3, 6, and 12 months of
      treatment. NCV-EMG results shown that patients with n-hexane poisoning have
      simultaneous damage on motor and sensory nerves, of which sensory nerve damage
      was more severe. Motor nerves of the lower limbs were severe damaged than those
      of the upper limbs; whereas injury of sensory nerve in the upper limbs was more
      severe than that of the lower limbs. After treatment, clinical signs and symptoms
      of the patients were significantly improved. NCV-EMG result showed a delayed
      worsening at 3 months then gradually recovered after 12 months. Recovery of the
      motor nerve was better compared with sensory nerve, with upper limbs faster than
      that of the lower limbs.

PMID- 24853720
TI  - Bioavailability comparison of a new form of vilazodone XVII to IV in beagles
      using liquid chromatography/mass spectrometry.
AB  - Vilazodone hydrochloride (CAS 163521-12-8) is polymorphic and has 15 crystal
      forms, referred to as I-XI and XIII-XVI. In the study, we prepared and performed
      structural identification of a new crystal form named XVII. To investigate this
      in vivo, a rapid and sensitive method based on liquid-liquid extraction, followed
      by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS)
      was developed and validated for the determination of vilazodone hydrochloride in
      dog plasma. This HPLC-MS/MS method was successfully applied to a bioavailability
      comparison of two crystal forms of vilazodone hydrochloride (IV and XVII) in six
      healthy beagles using a single-dose, two-way crossover design. The maximum plasma
      concentration (C(max)), the time taken to reach C(max), and the area under the
      concentration-time curve were determined following oral administration of 10 mg
      vilazodone hydrochloride (IV or XVII) to beagles. These analyses revealed no
      significant bioavailability differences between vilazodone hydrochloride forms IV
      and XVII in dogs.

PMID- 24853721
TI  - Hepatitis C virus infection in end-stage renal disease and kidney
      transplantation.
AB  - Liver disease secondary to chronic hepatitis C virus (HCV) infection is an
      important cause of morbidity and mortality in patients with end-stage renal
      disease (ESRD) on renal replacement therapy and after kidney transplantation
      (KT). Hemodialytic treatment (HD) for ESRD constitutes a risk factor for
      bloodborne infections because of prolonged vascular access and the potential for
      exposure to infected patients and contaminated equipment. Evaluation of HCV
      positive/ESRD and HCV-positive/KT patients is warranted to determine the stage of
      disease and the appropriateness of antiviral therapy, despite such treatment is
      challenging especially due to tolerability issues. Antiviral treatment with
      interferon (IFN) is contraindicated after transplantation due to the risk of
      rejection, and therefore, treatment is recommended before KT. Newer treatment
      strategies of direct-acting antiviral agents in combination are revolutionizing
      HCV therapy, as a result of encouraging outcomes streaming from recent studies
      which report increased sustained viral response, low or no resistance, and good
      safety profiles, including preservation of renal function. KT has been
      demonstrated to yield better outcomes with respect to remaining on HD although
      survival after KT is penalized by the presence of HCV infection with respect to
      HCV-negative transplant recipients. Therefore, an appropriate, comprehensive,
      easily applicable set of clinical practice management guidelines is necessary in
      both ESRD and KT patients with HCV infection and HCV-related liver disease. 

PMID- 24853722
TI  - Mercury and selenium ingestion rates of Atlantic leatherback sea turtles
      (Dermochelys coriacea): a cause for concern in this species?
AB  - Bodily accumulation of certain toxic elements can cause physiologic harm to
      marine organisms and be detrimental to their health and survival. The leatherback
      sea turtle (Dermochelys coriacea) is a broadly distributed marine reptile capable
      of consuming hundreds of kilograms of gelatinous zooplankton each day. Little is
      known about toxicants present in these prey items. Specifically, mercury is a
      known neurotoxin with no known essential function, while selenium detoxifies
      bodily mercury, but can be toxic at elevated concentrations. I collected 121
      leatherback prey items (i.e., gelatinous zooplankton) from known leatherback
      foraging grounds and sampled the esophagus and stomach contents of stranded
      turtles. All samples were analyzed for total mercury and selenium. Additionally,
      two prey items and three liver samples were analyzed for methylmercury, the most
      toxic form of the element. Total mercury concentrations in prey items ranged from
      0.2 to 17 ppb, while selenium concentrations ranged from <10 to 616 ppb;
      methylmercury concentrations in liver ranged from 25 to 236 ppb. Prey items had
      methylmercury concentrations below the limits of detection (<0.4 ppb). Hazard
      quotients and exposure rates indicate that leatherbacks of all life stages may be
      at risk for selenium toxicity. For endangered species like the leatherback,
      continued anthropogenic deposition of mercury and selenium into the environment
      is concerning, especially since bodily mercury and selenium concentrations
      increase as organisms age. Because leatherbacks are long-lived and have large
      daily prey consumption rates, mercury and selenium loads may increase to
      physiologically harmful levels in this imperiled species. 

PMID- 24853723
TI  - Calcitonin gene-related peptide modulates the production of pro-inflammatory
      cytokines associated with periprosthetic osteolysis by THP-1 macrophage-like
      cells.
AB  - OBJECTIVE: An anti-resorptive impact of the neuropeptide calcitonin gene-related
      peptide (CGRP) on periprosthetic osteolysis, the leading cause of early
      prosthesis loosening, has been shown previously. In this study, the impact of
      CGRP on pro-inflammatory cytokine production associated with periprosthetic
      osteolysis was analysed using THP-1 macrophage-like cells. METHODS: Cells were
      stimulated with ultra-high-molecular-weight polyethylene (UHMWPE) particles (cell
      to-particle ratios of 1:100 and 1:500) and lipopolysaccharides (LPS; 1 ug/ml) to
      establish osteolytic conditions, and simultaneously treated with CGRP (10(-8)M).
      Receptor activator of nuclear factor-kappaB (RANK), RANK ligand (RANKL) and
      tumour necrosis factor (TNF)-alpha mRNA expression were measured by quantitative
      RT-PCR. RANK protein was detected by Western blot. Secreted protein levels of TNF
      alpha as well as interleukin (IL)-1beta and IL-6 were quantified in cell culture
      supernatants by ELISA and Bio-Plex cytokine assay, respectively. RESULTS:
      Activation of macrophage-like cells failed to enhance the production of RANK but
      led to a dose- and time-dependent increase of TNF-alpha mRNA and secreted protein
      levels of TNF-alpha, IL-1beta and IL-6. Application of CGRP time-dependently
      suppressed TNF-alpha mRNA expression induced by low-particle concentrations and
      LPS, while both particle- and LPS-induced secretion of TNF-alpha was inhibited. A
      pronounced inhibitory effect of CGRP on LPS-induced cytokine production at 24 h
      of incubation was also observed with IL-1beta and IL-6. CONCLUSIONS: CGRP shows a
      time-dependent inhibitory effect on the secretion of osteolysis-associated pro
      inflammatory cytokines, indicating an indirect anti-resorptive influence of the
      neuropeptide on both aseptic prosthesis loosening and bacterially induced bone
      resorption which might enhance the life time of total joint replacements.

PMID- 24853724
TI  - Recognizing mild cognitive impairment based on network connectivity analysis of
      resting EEG with zero reference.
AB  - The diagnosis of mild cognitive impairment (MCI) is very helpful for early
      therapeutic interventions of Alzheimer's disease (AD). MCI has been proven to be
      correlated with disorders in multiple brain areas. In this paper, we used
      information from resting brain networks at different EEG frequency bands to
      reliably recognize MCI. Because EEG network analysis is influenced by the
      reference that is used, we also evaluate the effect of the reference choices on
      the resting scalp EEG network-based MCI differentiation. The conducted study
      reveals two aspects: (1) the network-based MCI differentiation is superior to the
      previously reported classification that uses coherence in the EEG; and (2) the
      used EEG reference influences the differentiation performance, and the zero
      approximation technique (reference electrode standardization technique, REST) can
      construct a more accurate scalp EEG network, which results in a higher
      differentiation accuracy for MCI. This study indicates that the resting scalp EEG
      based network analysis could be valuable for MCI recognition in the future. 

PMID- 24853725
TI  - Multiple roles of connexins in atherosclerosis- and restenosis-induced vascular
      remodelling.
AB  - Endothelial dysfunction is the initial step in atherosclerotic plaque development
      in large- and medium-sized arteries. This progressive disease, which starts
      during childhood, is characterized by the accumulation of lipids, macrophages,
      neutrophils, T lymphocytes and smooth muscle cells in the intima of the vessels.
      Erosion and rupture of the atherosclerotic plaque may induce myocardial
      infarction and cerebrovascular accidents, which are responsible for a large
      percentage of sudden deaths. The most common treatment for atherosclerosis is
      angioplasty and stent implantation, but these surgical interventions favour a
      vascular reaction called restenosis and the associated de-endothelialization
      increases the risk of thrombosis. This review provides an overview of the role of
      connexins, a large family of transmembrane proteins, in vascular remodelling
      associated with atherosclerosis and restenosis. The connexins expressed in the
      vascular wall are Cx37, Cx40, Cx43 and Cx45; their expressions vary with vascular
      territory and species. Connexins form hemichannels or gap junction channels,
      allowing the exchange of ions and small metabolites between the cytosol and
      extracellular space or between neighbouring cells, respectively. Connexins have
      important roles in vascular physiology; they support radial and longitudinal cell
      to-cell communication in the vascular wall, and significant changes in their
      expression patterns have been described during atherosclerosis and restenosis.

PMID- 24853726
TI  - Increased blood-brain barrier permeability on perfusion computed tomography
      predicts hemorrhagic transformation in acute ischemic stroke.
AB  - BACKGROUND/PURPOSE: Perfusion computed tomography (CT) is capable of measuring
      the permeability surface product (PS). PS reflects the permeability of the blood
      brain barrier, involved in the pathophysiology of hemorrhagic transformation (HT)
      of ischemic stroke. The aim of our study was to determine if an increased PS can
      predict HT. METHODS: A total of 86 patients with ischemic stroke were included.
      They underwent multimodality CT, including the measurement of PS. We compared the
      clinical and radiological characteristics of patients who developed HT to those
      who did not, using univariate analysis. Multivariate regression analyses were
      then used to determine HT predictors. RESULTS: HT was observed in 27 patients
      (31%). Infarct PS was significantly associated with HT (p = 0.047), as were
      atrial fibrillation (p = 0.03), admission National Institute of Health Stroke
      Scale score (p = 0.02), infarct volume (p = 0.0004), presence of large-vessel
      occlusion (p = 0.0005) and a poorer collateral status (p = 0.003). Using logistic
      regression modeling, an infarct PS >0.84 ml/100 g/min was an independent
      predictor of HT (OR 28, 95% CI 1.75-452.98; p = 0.02). Other independent
      predictors of HT were infarct volume and a history of atrial fibrillation.
      CONCLUSIONS: Our findings suggest that infarct PS can be a predictor of HT and
      may help clinicians to improve patient care around thrombolysis decisions in the
      acute phase of ischemic stroke.

PMID- 24853728
TI  - Pulmonary veno-occlusive disease: an 80-year-old mystery.
AB  - Pulmonary veno-occlusive disease (PVOD) is a rare form of pulmonary hypertension
      which occurs in 0.1-0.2 people per million. Its etiology is still poorly
      understood but is related to several risk factors. The histopathology of PVOD is
      characterized by intimal fibrosis narrowing or the occlusion of small pulmonary
      veins or venules. A definitive diagnosis requires a surgical biopsy, which is a
      risky procedure. Thus, the diagnosis must be based on high clinical suspicion and
      the results of various diagnostic tests, mainly high-resolution computed
      tomography, pulmonary function tests, bronchoalveolar lavage, and right heart
      catheterization. The definitive treatment is limited to lung transplantation.
      Several pulmonary arterial hypertension-specific agents may cause pulmonary edema
      in PVOD. However, the cautious use of such medications in selected patients, and
      surgical or mechanical supports, may successfully bridge patients to
      transplantation. Given the scant knowledge regarding this entity, future studies
      with a focus on elucidating the etiology and establishing the optimal treatment
      are required, as is further development in diagnosis.

PMID- 24853727
TI  - The cocktail boat.
AB  - We describe the inspiration, development, and deployment of a novel cocktail
      device modeled after a class of water-walking insects. Semi-aquatic insects like
      Microvelia and Velia evade predators by releasing a surfactant that quickly
      propels them across the water. We exploit an analogous propulsion mechanism in
      the design of an edible cocktail boat. We discuss how gradients in surface
      tension lead to motion across the water's surface, and detail the design
      considerations associated with the insect-inspired cocktail boat. 

PMID- 24853729
TI  - Magnetic and optoelectronic properties of gold nanocluster-thiophene assembly.
AB  - Nanohybrids consisting of Au nanocluster and polythiophene nanowire assemblies
      exhibit unique thermal-responsive optical behaviors and charge-transfer
      controlled magnetic and optoelectronic properties. The ultrasmall Au nanocluster
      enhanced photoabsorption and conductivity effectively improves the photocurrent
      of nanohybrid based photovoltaics, leading to an increase of power conversion
      efficiency by 14 % under AM 1.5 illumination. In addition, nanohybrids exhibit
      electric field controlled spin resonance and magnetic field sensing behaviors,
      which open up the potential of charge-transfer complex system where the magnetism
      and optoelectronics interact. 

PMID- 24853730
TI  - Collectivism culture, HIV stigma and social network support in Anhui, China: a
      path analytic model.
AB  - HIV stigma is rooted in culture and, therefore, it is essential to investigate it
      within the context of culture. The objective of this study was to examine the
      interrelationships among individualism-collectivism, HIV stigma, and social
      network support. A social network study was conducted among 118 people living
      with HIVAIDS in China, who were infected by commercial plasma donation, a
      nonstigmatized behavior. The Individualism-Collectivism Interpersonal Assessment
      Inventory (ICIAI) was used to measure cultural norms and values in the context of
      three social groups, family members, friends, and neighbors. Path analyses
      revealed (1) a higher level of family ICIAI was significantly associated with a
      higher level of HIV self-stigma (beta=0.32); (2) a higher level of friend ICIAI
      was associated with a lower level of self-stigma (beta=-035); (3) neighbor ICIAI
      was associated with public stigma (beta=-0.61); (4) self-stigman was associated
      with social support from neighbors (beta=-0.27); and (5) public stigma was
      associated with social support from neighbors (beta=-0.24). This study documents
      that HIV stigma may mediate the relationship between collectivist culture and
      social network support, providing an empirical basis for interventions to include
      aspects of culture into HIV intervention strategies.

PMID- 24853731
TI  - Fucoidan as an inhibitor of thermally induced collagen glycation examined by
      acetate electrophoresis.
AB  - Non-enzymatic glycation (Maillard reaction) in vitro could be a simple method to
      obtain glycoconjugates for studying their biological properties. Hence, fucoidan
      was retained by acetate electrophoresis indicating a strong interaction with the
      protein. A loss of colour in fucoidan bands was found for samples incubated with
      collagen as compared with samples of free fucoidan. Also under in vitro
      conditions at 100 degrees C - simulating a sudden burn incident - fucoidan binds
      with collagen as a result of the Maillard reaction. In contrast, the colour of
      the fucoidan bands intensified for samples incubated with collagen, with the
      addition of glucose. Electrophoretic analyses were carried out after heating the
      samples to a temperature simulating a burn incident. The bands were found to
      intensify for samples incubated with collagen during a 30-day-long incubation.
      Thus, spontaneous in vitro glycation - i.e. without the addition of glucose - was
      confirmed. This process is highly intensified both by the temperature and time of
      incubation. For a sample incubated in vitro in a fucoidan solution containing
      glucose, glycation was confirmed in a preliminary FTIR and acetate
      electrophoresis examinations, occurring in collagen obtained from chicken skins.
      In particular, a new band emerging around 1746 cm(-1) was observed for above
      samples, as was its increasing intensity, as compared with samples without the
      addition of glucose. In the collagen glycation assay, while glucose reacts with
      collagen and forms cross-linked aggregates, fucoidan decreases the process of
      aggregation and recovery of native collagen. 

PMID- 24853732
TI  - Piperlongumine as a potential activator of AMP-activated protein kinase in HepG2
      cells.
AB  - AMP-activated protein kinase (AMPK) is a key regulator of fatty acid biosynthesis
      and fatty acid oxidation throughout the body. Piperlongumine (PL) isolated from
      Piper longum (L.) was shown to potently upregulate activation of AMPK via
      phosphorylation and inactivation of acetyl-CoA carboxylases in cultured HepG2
      cells, presumably enhancing the transfer of fatty acids into mitochondrial cells
      by inhibiting malonyl-CoA production. PL showed cytotoxicity on HepG2 cell growth
      at the concentration of 5 MUM of PL, while more than 80% of HepG2 cells were
      survived at the concentration of 2 MUM of PL. Overall, the results of this study
      indicate that PL activates AMPK phosphorylation and possesses cytotoxicity in
      HepG2 cells. 

PMID- 24853733
TI  - Accelerating drug development through collaboration: the Hepatitis C Drug
      Development Advisory Group.
AB  - Over the past decade, landmark collaboration between regulatory agencies,
      pharmaceutical companies, academia, and patient community representatives has
      enabled the development and approval of new hepatitis C virus (HCV) treatment
      regimens with unprecedented speed. By providing a neutral platform for cross
      sector engagement, the Forum for Collaborative HIV Research's(1) HCV Drug
      Development Advisory Group played a critical role in fostering this collaboration
      and expediting drug development. The applicability of this model to other
      therapeutic areas should be explored. 

PMID- 24853735
TI  - The use of an endostapler in the treatment of supralevator abscess of
      intersphincteric origin.
AB  - AIM: This technical note describes the use of an endostapler for the definitive
      treatment of supralevator abscess upward from an intersphincteric origin. METHOD:
      A two-stage treatment was performed. First an endoanal drainage was performed by
      inserting a mushroom catheter in the supralevator abscess cavity. In the second
      stage transanal unroofing of the fistula was performed with an endostapler.
      RESULTS: Since 2011, three patients have been treated in this way. After 2 years
      of follow up, none of the patients had recurrence of the abscess or been referred
      for anal incontinence. CONCLUSION: The use of an endostapler in the treatment of
      supralevator abscess of intersphincteric origin may be an alternative to decrease
      the risk of recurrence and incontinence.

PMID- 24853736
TI  - Simplifying solid-state NMR spectra for biophysical studies on membrane proteins:
      selective targeting of sites and interactions.

PMID- 24853734
TI  - Genetic variants in transcription factors are associated with the
      pharmacokinetics and pharmacodynamics of metformin.
AB  - One-third of type 2 diabetes patients do not respond to metformin. Genetic
      variants in metformin transporters have been extensively studied as a likely
      contributor to this high failure rate. Here, we investigate, for the first time,
      the effect of genetic variants in transcription factors on metformin
      pharmacokinetics (PK) and response. Overall, 546 patients and healthy volunteers
      contributed their genome-wide, pharmacokinetic (235 subjects), and HbA1c data
      (440 patients) for this analysis. Five variants in specificity protein 1 (SP1), a
      transcription factor that modulates the expression of metformin transporters,
      were associated with changes in treatment HbA1c (P < 0.01) and metformin
      secretory clearance (P < 0.05). Population pharmacokinetic modeling further
      confirmed a 24% reduction in apparent clearance in homozygous carriers of one
      such variant, rs784888. Genetic variants in other transcription factors,
      peroxisome proliferator-activated receptor-alpha and hepatocyte nuclear factor 4
      alpha, were significantly associated with HbA1c change only. Overall, our study
      highlights the importance of genetic variants in transcription factors as
      modulators of metformin PK and response. 

PMID- 24853737
TI  - The proapoptotic protein tBid forms both superficially bound and membrane
      inserted oligomers.
AB  - Bid is a proapopotic activator protein of the Bcl-2 family that plays a pivotal
      role in controlling mitochondrial outer membrane permeabilization during
      apoptosis. Here, we characterized the interaction of fluorescently labeled
      truncated Bid (tBid) with a mitochondria-like supported lipid bilayer at the
      single-molecule level. The proteins observed at the membrane exhibited a very
      wide range of mobility. Confocal images of the membrane displayed both
      diffraction-limited Gaussian spots and horizontal streaks, corresponding to
      immobile and mobile tBid species, respectively. We observed 1), fast-diffusing
      proteins corresponding to a loosely, probably electrostatically bound state; 2),
      slowly diffusing proteins, likely corresponding to a superficially inserted
      state; and 3), fully immobilized proteins, suggesting a fully inserted state. The
      stoichiometry of these proteins was determined by normalizing their fluorescence
      intensity by the brightness of a tBid monomer, measured separately using
      fluorescence fluctuation techniques. Strikingly, the immobile species were found
      to be mainly tetramers and higher, whereas the mobile species had on average a
      significantly lower stoichiometry. Taken together, these results show that as
      soluble Bid progresses toward a membrane-inserted state, it undergoes an
      oligomerization process similar to that observed for Bax.

PMID- 24853738
TI  - Independent synchronized control and visualization of interactions between living
      cells and organisms.
AB  - To investigate the early stages of cell-cell interactions occurring between
      living biological samples, imaging methods with appropriate spatiotemporal
      resolution are required. Among the techniques currently available, those based on
      optical trapping are promising. Methods to image trapped objects, however, in
      general suffer from a lack of three-dimensional resolution, due to technical
      constraints. Here, we have developed an original setup comprising two independent
      modules: holographic optical tweezers, which offer a versatile and precise way to
      move multiple objects simultaneously but independently, and a confocal microscope
      that provides fast three-dimensional image acquisition. The optical decoupling of
      these two modules through the same objective gives users the possibility to
      easily investigate very early steps in biological interactions. We illustrate the
      potential of this setup with an analysis of infection by the fungus Drechmeria
      coniospora of different developmental stages of Caenorhabditis elegans. This has
      allowed us to identify specific areas on the nematode's surface where fungal
      spores adhere preferentially. We also quantified this adhesion process for
      different mutant nematode strains, and thereby derive insights into the host
      factors that mediate fungal spore adhesion.

PMID- 24853739
TI  - Molecular determinants of cardiac myocyte performance as conferred by isoform
      specific TnI residues.
AB  - Troponin I (TnI) is the molecular switch of the sarcomere. Cardiac myocytes
      express two isoforms of TnI during development. The fetal heart expresses the
      slow skeletal TnI (ssTnI) isoform and shortly after birth ssTnI is completely and
      irreversibly replaced by the adult cardiac TnI (cTnI) isoform. These two isoforms
      have important functional differences; broadly, ssTnI is a positive inotrope,
      especially under acidic/hypoxic conditions, whereas cTnI facilitates faster
      relaxation performance. Evolutionary directed changes in cTnI sequence suggest
      cTnI evolved to favor relaxation performance in the mammalian heart. To
      investigate the mechanism, we focused on several notable TnI isoform and trans
      species-specific residues located in TnI's helix 4 using structure/function and
      molecular dynamics analyses. Gene transduction of adult cardiac myocytes by cTnIs
      with specific helix 4 ssTnI substitutions, Q157R/A164H/E166V/H173N (QAEH), and
      A164H/H173N (AH), were investigated. cTnI QAEH is similar in these four residues
      to ssTnI and nonmammalian chordate cTnIs, whereas cTnI AH is similar to fish cTnI
      in these four residues. In comparison to mammalian cTnI, cTnI QAEH and cTnI AH
      showed increased contractility and slowed relaxation, which functionally mimicked
      ssTnI expressing myocytes. cTnI QAEH molecular dynamics simulations demonstrated
      altered intermolecular interactions between TnI helix 4 and cTnC helix A,
      specifically revealing a new, to our knowledge, electrostatic interaction between
      R171of cTnI and E15 of cTnC, which structurally phenocopied the ssTnI
      conformation. Free energy perturbation calculation of cTnC Ca(2+) binding for
      these conformations showed relative increased calcium binding for cTnI QAEH
      compared to cTnI. Taken together, to our knowledge, these new findings provide
      evidence that the evolutionary-directed coordinated acquisition of residues Q157,
      A164, E166, H173 facilitate enhanced relaxation performance in mammalian adult
      cardiac myocytes.

PMID- 24853740
TI  - Additive and synergistic membrane permeabilization by antimicrobial
      (lipo)peptides and detergents.
AB  - Certain antibiotic peptides are thought to permeabilize membranes of pathogens by
      effects that are also observed for simple detergents, such as membrane thinning
      and disordering, asymmetric bilayer expansion, toroidal pore formation, and
      micellization. Here we test the hypothesis that such peptides act additively with
      detergents when applied in parallel. Additivity is defined analogously to a
      fractional inhibitory concentration index of unity, and the extent and mechanism
      of leakage is measured by the fluorescence lifetime-based vesicle leakage assay
      using calcein-loaded vesicles. Good additivity was found for the concerted action
      of magainin 2, the fungicidal lipopeptide class of surfactins from Bacillus
      subtilis QST713, and the detergent octyl glucoside, respectively, with the
      detergent C12EO8. Synergistic or superadditive action was observed for fengycins
      from B. subtilis, as well as the detergent CHAPS, when combined with C12EO8. The
      results illustrate two mechanisms of synergistic action: First, maximal leakage
      requires an optimum degree of heterogeneity in the system that may be achieved by
      mixing a graded with an all-or-none permeabilizer. (The optimal perturbation
      should be focused to certain defect structures, yet not to the extent that some
      vesicles are not affected at all.) Second, a cosurfactant may enhance the
      bioavailability of a poorly soluble peptide. The results are important for
      understanding the concerted action of membrane-permeabilizing compounds in
      biology as well as for optimizing formulations of such antimicrobials for medical
      applications or crop protection.

PMID- 24853741
TI  - Probing the transmembrane structure and dynamics of microsomal NADPH-cytochrome
      P450 oxidoreductase by solid-state NMR.
AB  - NADPH-cytochrome P450 oxidoreductase (CYPOR) is an essential redox partner of the
      cytochrome P450 (cyt P450) superfamily of metabolic enzymes. In the endoplasmic
      reticulum of liver cells, such enzymes metabolize ~75% of the pharmaceuticals in
      use today. It is known that the transmembrane domain of CYPOR plays a crucial
      role in aiding the formation of a complex between CYPOR and cyt P450. Here we
      present the transmembrane structure, topology, and dynamics of the FMN binding
      domain of CYPOR in a native membrane-like environment. Our solid-state NMR
      results reveal that the N-terminal transmembrane domain of CYPOR adopts an alpha
      helical conformation in the lipid membrane environment. Most notably, we also
      show that the transmembrane helix is tilted ~13 degrees  from the lipid bilayer
      normal, and exhibits motions on a submillisecond timescale including rotational
      diffusion of the whole helix and fluctuation of the helical director axis. The
      approaches and the information reported in this study would enable further
      investigations on the structure and dynamics of the full-length NADPH-cytochrome
      P450 oxidoreductase and its interaction with other membrane proteins in a
      membrane environment.

PMID- 24853742
TI  - Conformational switching in PolyGln amyloid fibrils resulting from a single amino
      acid insertion.
AB  - The established correlation between neurodegenerative disorders and intracerebral
      deposition of polyglutamine aggregates motivates attempts to better understand
      their fibrillar structure. We designed polyglutamines with a few lysines inserted
      to overcome the hindrance of extreme insolubility and two D-lysines to limit the
      lengths of beta-strands. One is 33 amino acids long (PolyQKd-33) and the other
      has one fewer glutamine (PolyQKd-32). Both form well-dispersed fibrils suitable
      for analysis by electron microscopy. Electron diffraction confirmed cross-beta
      structures in both fibrils. Remarkably, the deletion of just one glutamine
      residue from the middle of the peptide leads to substantially different amyloid
      structures. PolyQKd-32 fibrils are consistently 10-20% wider than PolyQKd-33, as
      measured by negative staining, cryo-electron microscopy, and scanning
      transmission electron microscopy. Scanning transmission electron microscopy
      analysis revealed that the PolyQKd-32 fibrils have 50% higher mass-per-length
      than PolyQKd-33. This distinction can be explained by a superpleated beta
      structure model for PolyQKd-33 and a model with two beta-solenoid protofibrils
      for PolyQKd-32. These data provide evidence for beta-arch-containing structures
      in polyglutamine fibrils and open future possibilities for structure-based drug
      design.

PMID- 24853744
TI  - Slow axonemal dynein e facilitates the motility of faster dynein c.
AB  - We highly purified the Chlamydomonas inner-arm dyneins e and c, considered to be
      single-headed subspecies. These two dyneins reside side-by-side along the
      peripheral doublet microtubules of the flagellum. Electron microscopic
      observations and single particle analysis showed that the head domains of these
      two dyneins were similar, whereas the tail domain of dynein e was short and bent
      in contrast to the straight tail of dynein c. The ATPase activities, both basal
      and microtubule-stimulated, of dynein e (kcat = 0.27 s(-1) and kcat,MT = 1.09 s(
      1), respectively) were lower than those of dynein c (kcat = 1.75 s(-1) and
      kcat,MT = 2.03 s(-1), respectively). From in vitro motility assays, the apparent
      velocity of microtubule translocation by dynein e was found to be slow (Vap = 1.2
      +/- 0.1 MUm/s) and appeared independent of the surface density of the motors,
      whereas dynein c was very fast (Vmax = 15.8 +/- 1.5 MUm/s) and highly sensitive
      to decreases in the surface density (Vmin = 2.2 +/- 0.7 MUm/s). Dynein e was
      expected to be a processive motor, since the relationship between the microtubule
      landing rate and the surface density of dynein e fitted well with first-power
      dependence. To obtain insight into the in vivo roles of dynein e, we measured the
      sliding velocity of microtubules driven by a mixture of dynein e and c at various
      ratios. The microtubule translocation by the fast dynein c became even faster in
      the presence of the slow dynein e, which could be explained by assuming that
      dynein e does not retard motility of faster dyneins. In flagella, dynein e likely
      acts as a facilitator by holding adjacent microtubules to aid dynein c's power
      stroke.

PMID- 24853745
TI  - None of the rotor residues of F1-ATPase are essential for torque generation.
AB  - F1-ATPase is a powerful rotary molecular motor that can rotate an object several
      hundred times as large as the motor itself against the viscous friction of water.
      Forced reverse rotation has been shown to lead to ATP synthesis, implying that
      the mechanical work against the motor's high torque can be converted into the
      chemical energy of ATP. The minimal composition of the motor protein is
      alpha3beta3gamma subunits, where the central rotor subunit gamma turns inside a
      stator cylinder made of alternately arranged alpha3beta3 subunits using the
      energy derived from ATP hydrolysis. The rotor consists of an axle, a coiled coil
      of the amino- and carboxyl-terminal alpha-helices of gamma, which deeply
      penetrates the stator cylinder, and a globular protrusion that juts out from the
      stator. Previous work has shown that, for a thermophilic F1, significant portions
      of the axle can be truncated and the motor still rotates a submicron sized bead
      duplex, indicating generation of up to half the wild-type (WT) torque. Here, we
      inquire if any specific interactions between the stator and the rest of the rotor
      are needed for the generation of a sizable torque. We truncated the protruding
      portion of the rotor and replaced part of the remaining axle residues such that
      every residue of the rotor has been deleted or replaced in this or previous
      truncation mutants. This protrusionless construct showed an unloaded rotary speed
      about a quarter of the WT, and generated one-third to one-half of the WT torque.
      No residue-specific interactions are needed for this much performance. F1 is so
      designed that the basic rotor-stator interactions for torque generation and
      control of catalysis rely solely upon the shape and size of the rotor at very low
      resolution. Additional tailored interactions augment the torque to allow ATP
      synthesis under physiological conditions.

PMID- 24853743
TI  - The thermodynamics of general and local anesthesia.
AB  - General anesthetics are known to cause depression of the freezing point of
      transitions in biomembranes. This is a consequence of ideal mixing of the
      anesthetic drugs in the membrane fluid phase and exclusion from the solid phase.
      Such a generic law provides physical justification of the famous Meyer-Overton
      rule. We show here that general anesthetics, barbiturates, and local anesthetics
      all display the same effect on melting transitions. Their effect is reversed by
      hydrostatic pressure. Thus, the thermodynamic behavior of local anesthetics is
      very similar to that of general anesthetics. We present a detailed thermodynamic
      analysis of heat capacity profiles of membranes in the presence of anesthetics.
      Using this analysis, we are able to describe experimentally observed calorimetric
      profiles and predict the anesthetic features of arbitrary molecules. In addition,
      we discuss the thermodynamic origin of the cutoff effect of long-chain alcohols
      and the additivity of the effect of general and local anesthetics.

PMID- 24853746
TI  - Effects of the protonation state of the EEEE motif of a bacterial Na(+)-channel
      on conduction and pore structure.
AB  - A distinctive feature of prokaryotic Na(+)-channels is the presence of four
      glutamate residues in their selectivity filter. In this study, how the structure
      of the selectivity filter, and the free-energy profile of permeating Na(+) ions
      are altered by the protonation state of Glu177 are analyzed. It was found that
      protonation of a single glutamate residue was enough to modify the conformation
      of the selectivity filter and its conduction properties. Molecular dynamics
      simulations revealed that Glu177 residues may adopt two conformations, with the
      side chain directed toward the extracellular entrance of the channel or the
      intracellular cavity. The likelihood of the inwardly directed arrangement
      increases when Glu177 residues are protonated. The presence of one glutamate
      residue with its chain directed toward the intracellular cavity increases the
      energy barrier for translocation of Na(+) ions. These higher-energy barriers
      preclude Na(+) ions to permeate the selectivity filter of prokaryotic Na(+)
      channels when one or more Glu177 residues are protonated.

PMID- 24853747
TI  - Characterization of the connexin45 carboxyl-terminal domain structure and
      interactions with molecular partners.
AB  - Mechanisms underlying the initiation and persistence of lethal cardiac rhythms
      are of significant clinical and scientific interests. Gap junctions are
      principally involved in forming the electrical connections between myocytes, and
      changes in distribution, density, and properties are consistent characteristics
      in arrhythmic heart disease. Therefore, understanding the structure and function
      of gap junctions during normal and abnormal impulse propagation are essential in
      the control of arrhythmias. For example, Cx45 is predominately expressed in the
      specialized myocytes of the impulse generation and conduction system. In both
      ventricular and atrial human working myocytes, Cx45 is present in very low
      quantities. However, a reduction in Cx43 coupled with an increased Cx45 protein
      levels within the ventricles have been observed after myocardial infarction and
      end-stage heart failure. Cx45 may influence electrical and/or metabolic coupling
      as a result of pathophysiological overexpression. Our goal was to identify
      mechanisms that could cause cellular coupling to be different between the cardiac
      connexins. Based upon the conserved transmembrane and extracellular loop
      segments, our focus was on identifying features within the divergent cytoplasmic
      portions. Here, we biophysically characterize the carboxyl-terminal domain of
      Cx45 (Cx45CT). Purification revealed the possibility of oligomeric species, which
      was confirmed by analytical ultracentrifugation experiments. Sedimentation
      equilibrium and circular dichroism studies of different Cx45CT constructs
      identified one region of alpha-helical structure (A333-N361) that mediates CT
      dimerization through hydrophobic contacts. Interestingly, the binding affinity of
      Cx45CT dimerization is 1000-fold stronger than Cx43CT dimerization. Cx45CT
      resonance assignments were also used to identify the binding sites and affinities
      of molecular partners involved in the Cx45 regulation; although none disrupted
      dimerization, many of these proteins interacted within one intrinsically
      disordered region (P278-P285). This domain has similarities with other cardiac
      connexins, and we propose they constitute a master regulatory domain, which
      contains overlapping molecular partner binding, cis-trans proline isomerization,
      and phosphorylation sites.

PMID- 24853749
TI  - Distinct features of the histone core structure in nucleosomes containing the
      histone H2A.B variant.
AB  - Nucleosomes containing a human histone variant, H2A.B, in an aqueous solution
      were analyzed by small-angle neutron scattering utilizing a contrast variation
      technique. Comparisons with the canonical H2A nucleosome structure revealed that
      the DNA termini of the H2A.B nucleosome are detached from the histone core
      surface, and flexibly expanded toward the solvent. In contrast, the histone tails
      are compacted in H2A.B nucleosomes compared to those in canonical H2A
      nucleosomes, suggesting that they bind to the surface of the histone core and/or
      DNA. Therefore, the histone tail dynamics may function to regulate the
      flexibility of the DNA termini in the nucleosomes.

PMID- 24853748
TI  - Spatial organization of EphA2 at the cell-cell interface modulates trans
      endocytosis of ephrinA1.
AB  - EphA2 is a receptor tyrosine kinase (RTK) that is sensitive to spatial and
      mechanical aspects of the cell's microenvironment. Misregulation of EphA2 occurs
      in many aggressive cancers. Although its juxtacrine signaling geometry (EphA2's
      cognate ligand ephrinA1 is expressed on the surface of an apposing cell) provides
      a mechanism by which the receptor may experience extracellular forces, this also
      renders the system challenging to decode. By depositing living cells on synthetic
      supported lipid membranes displaying ephrinA1, we have reconstituted key features
      of the juxtacrine EphA2-ephrinA1 signaling system while maintaining the ability
      to perturb the spatial and mechanical properties of the membrane-cell interface
      with precision. In addition, we developed a trans-endocytosis assay to monitor
      internalization of ephrinA1 from a supported membrane into the apposing cell
      using a quantitative three-dimensional fluorescence microscopy assay. Using this
      experimental platform to mimic a cell-cell junction, we found that the signaling
      complex is not efficiently internalized when lateral reorganization at the
      membrane-cell contact sites is physically hindered. This suggests that EphA2
      ephrinA1 trans-endocytosis is sensitive to the mechanical properties of a cell's
      microenvironment and may have implications in physical aspects of tumor biology.

PMID- 24853750
TI  - Growing yeast into cylindrical colonies.
AB  - Microorganisms often form complex multicellular assemblies such as biofilms and
      colonies. Understanding the interplay between assembly expansion, metabolic
      yield, and nutrient diffusion within a freely growing colony remains a challenge.
      Most available data on microorganisms are from planktonic cultures, due to the
      lack of experimental tools to control the growth of multicellular assemblies.
      Here, we propose a method to constrain the growth of yeast colonies into simple
      geometric shapes such as cylinders. To this end, we designed a simple, versatile
      culture system to control the location of nutrient delivery below a growing
      colony. Under such culture conditions, yeast colonies grow vertically and only at
      the locations where nutrients are delivered. Colonies increase in height at a
      steady growth rate that is inversely proportional to the cylinder radius. We show
      that the vertical growth rate of cylindrical colonies is not defined by the
      single-cell division rate, but rather by the colony metabolic yield. This
      contrasts with cells in liquid culture, in which the single-cell division rate is
      the only parameter that defines the population growth rate. This method also
      provides a direct, simple method to estimate the metabolic yield of a colony. Our
      study further demonstrates the importance of the shape of colonies on setting
      their expansion. We anticipate that our approach will be a starting point for
      elaborate studies of the population dynamics, evolution, and ecology of microbial
      colonies in complex landscapes.

PMID- 24853751
TI  - Voltage and calcium dynamics both underlie cellular alternans in cardiac
      myocytes.
AB  - Cardiac alternans, a putative trigger event for cardiac reentry, is a beat-to
      beat alternation in membrane potential and calcium transient. Alternans was
      originally attributed to instabilities in transmembrane ion channel dynamics
      (i.e., the voltage mechanism). As of this writing, the predominant view is that
      instabilities in subcellular calcium handling are the main underlying mechanism.
      That being said, because the voltage and calcium systems are bidirectionally
      coupled, theoretical studies have suggested that both mechanisms can contribute.
      To date, to our knowledge, no experimental evidence of such a dual role within
      the same cell has been reported. Here, a combined electrophysiological and
      calcium imaging approach was developed and used to illuminate the contributions
      of voltage and calcium dynamics to alternans. An experimentally feasible
      protocol, quantification of subcellular calcium alternans and restitution slope
      during cycle-length ramping alternans control, was designed and validated. This
      approach allows simultaneous illumination of the contributions of voltage and
      calcium-driven instability to total cellular instability as a function of cycle
      length. Application of this protocol in in vitro guinea-pig left-ventricular
      myocytes demonstrated that both voltage- and calcium-driven instabilities
      underlie alternans, and that the relative contributions of the two systems change
      as a function of pacing rate.

PMID- 24853752
TI  - A computational model for the loss of neuronal organization in microcolumns.
AB  - A population of neurons in the cerebral cortex of humans and other mammals
      organize themselves into vertical microcolumns perpendicular to the pial surface.
      Anatomical changes to these microcolumns have been correlated with neurological
      diseases and normal aging; in particular, in area 46 of the rhesus monkey brain,
      the strength of microcolumns was shown to decrease with age. These changes can be
      caused by alterations in the spatial distribution of the neurons in microcolumns
      and/or neuronal loss. Using a three-dimensional computational model of neuronal
      arrangements derived from thin tissue sections and validated in brain tissue from
      rhesus monkeys, we show that neuronal loss is inconsistent with the findings in
      aged individuals. In contrast, a model of simple random neuronal displacements,
      constrained in magnitude by restorative harmonic forces, is consistent with
      observed changes and provides mechanistic insights into the age-induced loss of
      microcolumnar structure. Connection of the model to normal aging and disease are
      discussed.

PMID- 24853753
TI  - Fluid shear stress increases neutrophil activation via platelet-activating
      factor.
AB  - Leukocyte exposure to hemodynamic shear forces is critical for physiological
      functions including initial adhesion to the endothelium, the formation of
      pseudopods, and migration into tissues. G-protein coupled receptors on
      neutrophils, which bind to chemoattractants and play a role in neutrophil
      chemotaxis, have been implicated as fluid shear stress sensors that control
      neutrophil activation. Recently, exposure to physiological fluid shear stresses
      observed in the microvasculature was shown to reduce neutrophil activation in the
      presence of the chemoattractant formyl-methionyl-leucyl-phenylalanine. Here,
      however, human neutrophil preexposure to uniform shear stress (0.1-2.75
      dyn/cm(2)) in a cone-and-plate viscometer for 1-120 min was shown to increase,
      rather than decrease, neutrophil activation in the presence of platelet
      activating factor (PAF). Fluid shear stress exposure increased PAF-induced
      neutrophil activation in terms of L-selectin shedding, alphaMbeta2 integrin
      activation, and morphological changes. Neutrophil activation via PAF was found to
      correlate with fluid shear stress exposure, as neutrophil activation increased in
      a shear stress magnitude- and time-dependent manner. These results indicate that
      fluid shear stress exposure increases neutrophil activation by PAF, and, taken
      together with previous observations, differentially controls how neutrophils
      respond to chemoattractants.

PMID- 24853754
TI  - Interactions between distant ceRNAs in regulatory networks.
AB  - Competing endogenous RNAs (ceRNAs) were recently introduced as RNA transcripts
      that affect each other's expression level through competition for their microRNA
      (miRNA) coregulators. This stems from the bidirectional effects between miRNAs
      and their target RNAs, where a change in the expression level of one target
      affects the level of the miRNA regulator, which in turn affects the level of
      other targets. By the same logic, miRNAs that share targets compete over binding
      to their common targets and therefore also exhibit ceRNA-like behavior. Taken
      together, perturbation effects could propagate in the posttranscriptional
      regulatory network through a path of coregulated targets and miRNAs that share
      targets, suggesting the existence of distant ceRNAs. Here we study the prevalence
      of distant ceRNAs and their effect in cellular networks. Analyzing the network of
      miRNA-target interactions deciphered experimentally in HEK293 cells, we show that
      it is a dense, intertwined network, suggesting that many nodes can act as distant
      ceRNAs of one another. Indeed, using gene expression data from a perturbation
      experiment, we demonstrate small, yet statistically significant, changes in gene
      expression caused by distant ceRNAs in that network. We further characterize the
      magnitude of the propagated perturbation effect and the parameters affecting it
      by mathematical modeling and simulations. Our results show that the magnitude of
      the effect depends on the generation and degradation rates of involved miRNAs and
      targets, their interaction rates, the distance between the ceRNAs and the
      topology of the network. Although demonstrated for a miRNA-mRNA regulatory
      network, our results offer what to our knowledge is a new view on various
      posttranscriptional cellular networks, expanding the concept of ceRNAs and
      implying possible distant cross talk within the network, with consequences for
      the interpretation of indirect effects of gene perturbation.

PMID- 24853755
TI  - New insights on human skeletal muscle tissue compartments revealed by in vivo t2
      NMR relaxometry.
AB  - The spin-spin (T2) relaxation of (1)H-NMR signals in human skeletal muscle has
      been previously hypothesized to reveal information about myowater
      compartmentation. Although experimental support has been provided, no consensus
      has yet emerged concerning the attribution of specific anatomical compartments to
      the observed T2 components. Potential application of a noninvasive tool that
      might offer such information urges the quest for a definitive answer to this
      question. The purpose of this work was to obtain new information that might help
      elucidate the mechanism of T2 distribution in muscle. To do so, in vivo T2
      relaxation data was acquired from the soleus of eight healthy volunteers using a
      localized Carr-Purcell-Meiboom-Gill technique. Each acquisition contained 1000
      echoes with an interecho spacing of 1 ms. Data were acquired from each subject
      under different vascular filling preparations expected to change exclusively the
      extracellular water fraction. Two exponential components were systematically
      observed: an intermediate component (T2 ~ 32 ms) and a long component (100 < T2 <
      210 ms). The relative fraction and T2 value characterizing the long component
      systematically increased after progressive augmentation of extracellular water
      volume. Characteristic relaxation behavior for each vascular filling condition
      was analyzed with a two-site exchange model and a three-site two-exchange model.
      We show that a two-site exchange model can only predict the observations for
      small exchange rates, much more representative of transendothelial than
      transcytolemmal exchange regimes. The three-site two-exchange model representing
      the intracellular, interstitial, and vascular spaces was capable of precisely
      predicting the observations for realistic transcytolemmal and transendothelial
      exchange rates. The estimated intrinsic relative fractions of each of these
      compartments corroborate with estimations from previous works and strongly
      suggest that the T2 relaxation from water within the intracellular and
      interstitial spaces is described by the intermediate component, whereas the long
      component represents water within the vascular space.

PMID- 24853756
TI  - Negative feedback synchronizes islets of Langerhans.
AB  - Insulin is released from the pancreas in pulses with a period of ~ 5 min. These
      oscillatory insulin levels are essential for proper liver utilization and
      perturbed pulsatility is observed in type 2 diabetes. What coordinates the many
      islets of Langerhans throughout the pancreas to produce unified oscillations of
      insulin secretion? One hypothesis is that coordination is achieved through an
      insulin-dependent negative feedback action of the liver onto the glucose level.
      This hypothesis was tested in an in vitro setting using a microfluidic system
      where the population response from a group of islets was input to a model of
      hepatic glucose uptake, which provided a negative feedback to the glucose level.
      This modified glucose level was then delivered back to the islet chamber where
      the population response was again monitored and used to update the glucose
      concentration delivered to the islets. We found that, with appropriate parameters
      for the model, oscillations in islet activity were synchronized. This approach
      demonstrates that rhythmic activity of a population of physically uncoupled
      islets can be coordinated by a downstream system that senses islet activity and
      supplies negative feedback. In the intact animal, the liver can play this role of
      the coordinator of islet activity.

PMID- 24853757
TI  - Detecting subtle plasma membrane perturbation in living cells using second
      harmonic generation imaging.
AB  - The requirement of center asymmetry for the creation of second harmonic
      generation (SHG) signals makes it an attractive technique for visualizing changes
      in interfacial layers such as the plasma membrane of biological cells. In this
      article, we explore the use of lipophilic SHG probes to detect minute
      perturbations in the plasma membrane. Three candidate probes, Di-4-ANEPPDHQ (Di
      4), FM4-64, and all-trans-retinol, were evaluated for SHG effectiveness in Jurkat
      cells. Di-4 proved superior with both strong SHG signal and limited bleaching
      artifacts. To test whether rapid changes in membrane symmetry could be detected
      using SHG, we exposed cells to nanosecond-pulsed electric fields, which are
      believed to cause formation of nanopores in the plasma membrane. Upon nanosecond
      pulsed electric fields exposure, we observed an instantaneous drop of ~50% in SHG
      signal from the anodic pole of the cell. When compared to the simultaneously
      acquired fluorescence signals, it appears that the signal change was not due to
      the probe diffusing out of the membrane or changes in membrane potential or
      fluidity. We hypothesize that this loss in SHG signal is due to disruption in the
      interfacial nature of the membrane. The results show that SHG imaging has great
      potential as a tool for measuring rapid and subtle plasma membrane disturbance in
      living cells.

PMID- 24853758
TI  - Genetic and chemical analyses reveal that trypanothione synthetase but not
      glutathionylspermidine synthetase is essential for Leishmania infantum.
AB  - Trypanothione is a unique and essential redox metabolite of trypanosomatid
      parasites, the biosynthetic pathway of which is regarded as a promising target
      for antiparasitic drugs. Synthesis of trypanothione occurs by the consecutive
      conjugation of two glutathione molecules to spermidine. Both reaction steps are
      catalyzed by trypanothione synthetase (TRYS), a molecule known to be essential in
      Trypanosoma brucei. However, other trypanosomatids (including some Leishmania
      species and Trypanosoma cruzi) potentially express one additional enzyme,
      glutathionylspermidine synthetase (GSPS), capable of driving the first step of
      trypanothione synthesis yielding glutathionylspermidine. Because this monothiol
      can substitute for trypanothione in some reactions, the possibility existed that
      TRYS was redundant in parasites harboring GSPS. To clarify this issue, the
      functional relevance of both GSPS and TRYS was investigated in Leishmania
      infantum (Li). Employing a gene-targeting approach, we generated a gsps(-/-)
      knockout line, which was viable and capable of replicating in both life cycle
      stages of the parasite, thus demonstrating the superfluous role of LiGSPS. In
      contrast, elimination of both LiTRYS alleles was not possible unless parasites
      were previously complemented with an episomal copy of the gene. Retention of
      extrachromosomal LiTRYS in the trys(-/-)/+TRYS line after several passages in
      culture further supported the essentiality of this gene for survival of L.
      infantum (including its clinically relevant stage), hence ruling out the
      hypothesis of functional complementation by LiGSPS. Chemical targeting of LiTRYS
      with a drug-like compound was shown to also lead to parasite death. Overall, this
      study disqualifies GSPS as a target for drug development campaigns and, by
      genetic and chemical evidence, validates TRYS as a chemotherapeutic target in a
      parasite endowed with GSPS and, thus, probably along the entire trypanosomatid
      lineage. 

PMID- 24853759
TI  - Hypothyroidism-associated missense mutation impairs NADPH oxidase activity and
      intracellular trafficking of Duox2.
AB  - In the thyroid gland Duox2-derived H2O2 is essential for thyroid hormone
      biosynthesis. Several patients were identified with partial or severe iodide
      organification defects caused by mutation in the gene for Duox2 or its maturation
      factor, DuoxA2. A Duox2-deficient (Duox2(thyd)) mouse model enabled in vivo
      investigation of its critical function in thyroid tissues, but its roles proposed
      in host defense or other innate responses in nonthyroid tissues remain less
      certain. These mice carry a spontaneous DUOX2 missense mutation, a T->G
      transversion, in exon 16 that changes the highly conserved valine 674 to glycine
      and results in severe congenital hypothyroidism. The exact mechanism underlying
      the effects of the V674G mutation has not been elucidated at the molecular or
      cellular level. To determine how the V674G mutation leads to congenital
      hypothyroidism, we introduced the same mutation into human Duox2 or Duox1 cDNAs
      and expressed them in HEK-293 cells stably expressing the corresponding DuoxA
      proteins. We found that the valine->glycine mutant Duox proteins fail to produce
      H2O2, lose their plasma membrane localization pattern, and are retained within
      the endoplasmic reticulum. The Duox2 mutant binds to DuoxA2, but appears to be
      unstable owing to this retention. Immunohistochemical staining of Duox2 in murine
      salivary gland ducts showed that Duox2 in mutant mice loses its condensed apical
      plasma membrane localization pattern characteristic of wild-type Duox2 and
      accumulates in punctate vesicular structures within cells. Our findings
      demonstrate that changing the highly conserved valine 674 in Duox2 leads to
      impaired subcellular targeting and reactive oxygen species release required for
      hormonogenesis, resulting in congenital hypothyroidism. 

PMID- 24853760
TI  - Two natural products, trans-phytol and (22E)-ergosta-6,9,22-triene
      3beta,5alpha,8alpha-triol, inhibit the biosynthesis of estrogen in human ovarian
      granulosa cells by aromatase (CYP19).
AB  - Aromatase is the only enzyme in vertebrates to catalyze the biosynthesis of
      estrogens. Although inhibitors of aromatase have been developed for the treatment
      of estrogen-dependent breast cancer, the whole-body inhibition of aromatase
      causes severe adverse effects. Thus, tissue-selective aromatase inhibitors are
      important for the treatment of estrogen-dependent cancers. In this study, 63
      natural products with diverse structures were examined for their effects on
      estrogen biosynthesis in human ovarian granulosa-like KGN cells. Two compounds
      trans-phytol (SA-20) and (22E)-ergosta-6,9,22-triene-3beta,5alpha,8alpha-triol
      (SA-48)-were found to potently inhibit estrogen biosynthesis (IC50: 1MUM and
      0.5MUM, respectively). Both compounds decreased aromatase mRNA and protein
      expression levels in KGN cells, but had no effect on the aromatase catalytic
      activity in aromatase-overexpressing HEK293A cells and recombinant expressed
      aromatase. The two compounds decreased the expression of aromatase promoter
      I.3/II. Neither compound affected intracellular cyclic AMP (cAMP) levels, but
      they inhibited the phosphorylation or protein expression of cAMP response element
      binding protein (CREB). The effects of these two compounds on extracellular
      regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38 mitogen-activated
      protein kinases (MAPKs), and AKT/phosphoinositide 3-kinase (PI3K) pathway were
      examined. Inhibition of p38 MAPK could be the mechanism underpinning the actions
      of these compounds. Our results suggests that natural products structurally
      similar to SA-20 and SA-48 may be a new source of tissue-selective aromatase
      modulators, and that p38 MAPK is important in the basal control of aromatase in
      ovarian granulosa cells. SA-20 and SA-48 warrant further investigation as new
      pharmaceutical tools for the prevention and treatment of estrogen-dependent
      cancers. 

PMID- 24853761
TI  - Aqueous extract of unfermented honeybush (Cyclopia maculata) attenuates STZ
      induced diabetes and beta-cell cytotoxicity.
AB  - New strategies, which include beta-cell protection, are required in the treatment
      of T2D, as current drugs demonstrate little or no capacity to directly protect
      the vulnerable beta-cell against diabetes-induced cytotoxicity. In this study we
      investigated the ameliorative effect of pre-treatment with an aqueous extract of
      unfermented Cyclopia maculata (honeybush) on STZ-induced diabetes and pancreatic
      beta-cell cytotoxicity in Wistar rats after demonstrating a protective effect in
      vitro in RIN-5F cells. The amelioration of STZ-induced diabetes was seen in the
      reduction of the area under the curve, determined by the oral glucose tolerance
      test, as well as fasting glucose levels in extract-treated rats. Pre-treatment
      with extract also improved serum triglyceride levels and the glucose-to-insulin
      ratio. Pre-treatment with the extract or the drug, metformin, increased the beta
      cell area in islets, with a concomitant increase in beta-cell proliferation at
      the higher extract dose (300 mg/kg/d), but not the lower dose (30 mg/kg/d).
      Subsequently, the in vitro tritiated thymidine incorporation assay showed that
      the extract was not mitogenic in RIN-5F cells. STZ-induced elevation of plasma
      nitrite levels was reduced in extract-treated rats, but no changes were observed
      in their serum catalase, serum glutathione, liver lipid peroxidation and liver
      nitrotyrosine levels. Pre-treating the rats with extract ameliorated the diabetic
      effect of STZ in Wistar rats, with evidence of pancreatic beta-cells protection,
      attributed to the presence of high levels of antioxidants such as the xanthones,
      mangiferin and isomangiferin.

PMID- 24853762
TI  - Evidence for the involvement of JAK/STAT/SOCS pathway in the mechanism of
      Tangshen formula-treated diabetic nephropathy.
AB  - Diabetic nephropathy is one of the most significant microvascular complications
      associated with diabetes. Until now, there is no effective treatment and the gene
      mechanism of diabetic nephropathy is still unclear. Tangshen formula is a
      traditional Chinese medicine, and has been shown to have good clinical efficacy
      in diabetic nephropathy treatment. The objective of this study was to investigate
      the changes of gene expression profiling and explore the molecular mechanism
      using a db/db mice model treated by Tangshen formula. After administration for 12
      weeks, a microarray was applied to detect the gene expression of db/db mice
      kidney tissues. Quantitative real-time PCR was used to confirm the differential
      gene expression and carry out a JAK/STAT/SOCS signaling pathway study. Treatment
      with Tangshen formula reduced the levels of serum glucose and urinary albumin in
      db/db mice, and the effects of Tangshen formula on db/db mice were significantly
      different from the positive control (Losartan potassium tablets) on microarray
      data. It also showed that the JAK/STAT/SOCS signaling pathway played an important
      role in the treatment process. The expressions of JAK1, JAK2, and STAT3 were
      upregulated, and STAT4 was downregulated in Tangshen formula-treated db/db mice.
      SOCS1, 3, and 7 were all activated, while negative feedback regulated other
      related genes in the JAK/STAT/SOCS pathway. Our study suggested that Tangshen
      formula has beneficial effects on diabetic nephropathy treatment via regulating
      the JAK/STAT/SOCS signaling pathway. This study will help to provide evidence
      based recommendations for Tangshen formula clinical treatment.

PMID- 24853763
TI  - Horsfiequinones A-F, dimeric diarylpropanoids from Horsfieldia tetratepala.
AB  - A new diarylpropanoid, horsfiequinone A (1), and five new dimeric
      diarylpropanoids with 1,4-p-benzoquinone residue, horsfiequinones B-F (2-6),
      along with a known compound, combrequinone B (7), were isolated from Horsfieldia
      tetratepala. Their structures were elucidated by means of spectroscopic analysis.
      Horsfiequinones B-F (2-6), isolated as enantiomer mixtures with unequal
      proportions, were verified by analysis on a chiral OD-H HPLC column. Cytotoxicity
      evaluation against five human tumor lines showed selective inhibitory effects on
      HL-60 for several compounds tested with IC50 values ranging from 3.18 +/- 0.67 to
      6.61 +/- 0.08 uM.

PMID- 24853764
TI  - Triterpene saponins from the stems of Entada phaseoloides.
AB  - Ten new triterpene saponins (1-10) have been isolated from the stems of Entada
      phaseoloides. Their structures were elucidated by spectroscopic analysis and
      chemical methods. Among these compounds, the aglycons of 6-10 are being reported
      for the first time, in this study, including 3beta,15alpha,16alpha-trihydroxy
      11alpha,12alpha-epoxy olean-28,13beta-olide (6), 3beta,15alpha,16alpha-trihydroxy
      11-oxo-olean-12-en-28-oic acids (7 and 8), and 3beta,15alpha,16alpha-trihydroxy
      oleana-11,13(18)-dien-28-oic acids (9 and 10). The cytotoxic activities of all of
      these compounds were evaluated against HepG-2, A549, and Ec-1 cell lines.

PMID- 24853765
TI  - Paediatric epilepsy surgery in the posterior cortex: a study of 62 cases.
AB  - Past surgical series have emphasized the diagnostic complexity of posterior
      cortex epilepsy. Available data are sparse, especially in children, and most
      published series report a high number of surgical failures and post-operative
      neurological deficits. In this article, we present a paediatric cohort of 62
      children who underwent surgery for drug resistant posterior cortex epilepsy
      before the age of 16 years with a mean post-operative follow-up of 6.94 years
      (range: 2-16). Mean age at epilepsy onset was 3.2 years and 28 children (45%) had
      onset before 1 year of age. The mean age at surgery was 7.9 years (range: 1-16).
      Daily seizures were present in 63% of children. MRI was positive in 58 cases
      (93.5%) and invasive stereo-EEG was judged mandatory in 24/62 (39%) of patients.
      Surgery was confined to the parietal lobe in 11 children, the occipital lobe in
      8, the occipito-parietal region in four, the occipito-temporal region in 18, and
      involved both the temporal and parietal lobes in the remaining 21. Following
      surgery, 53 subjects (85.5%) remained seizure-free and among those who underwent
      a SEEG procedure, 75% achieved seizure freedom. Focal cortical dysplasia was the
      most frequent histopathological diagnosis (50%), followed by tumoural (24%) and
      gliotic lesions (14.5%). An older age at epilepsy onset, the presence of a rather
      restricted epileptogenic area, and a complete resection of the epileptogenic zone
      were predictive of a favourable surgical outcome. These results demonstrate that
      a good surgical outcome is possible in children with drug resistant posterior
      cortex epilepsy. Accurate analysis of the chronology of ictal semiology and
      electrophysiological features, viewed in the context of the complete
      electroclinical pattern, provides a topographical orientation for posterior
      cortex epilepsy and, together with the presence of a lesion detectable on
      imaging, may improve the rate of surgical success of posterior cortex epilepsy at
      paediatric age. 

PMID- 24853767
TI  - Structure-based de novo design and identification of D816V mutant-selective c-KIT
      inhibitors.
AB  - To identify potent and selective inhibitors of D816V, the most common gain-of
      function c-KIT mutant, we carried out structure-based de novo design using 7
      azaindole as the core and the scoring function improved by implementing an
      accurate solvation free energy term. This approach led to the identification of
      new c-KIT inhibitors specific for the D816V mutant. The 3-(3,4-dimethoxyphenyl)-7
      azaindole scaffold was optimized and represents a lead structure for the design
      of the potent and specific inhibitors of the D816V mutant. The results of
      molecular dynamics simulations indicate that hydrogen bonding interactions
      between the 7-azadindole moiety and the backbone groups of Cys673 are the most
      significant determinant for the potency and selectivity of c-KIT inhibitors. 

PMID- 24853769
TI  - Slow magnetic relaxation in octahedral cobalt(II) field-induced single-ion magnet
      with positive axial and large rhombic anisotropy.
AB  - Pseudooctahedral mononuclear cobat(II) complex [Co(abpt)2(tcm)2] (1), where abpt
      = 4-amino-3,5-bis(2-pyridyl)-1,2,4-triazole and tcm = tricyanomethanide anion,
      shows field-induced slow relaxation of magnetization with U = 86.2 K and large
      axial and rhombic single-ion zero-field-splitting parameters, D = +48(2) cm(-1)
      and E/D = 0.27(2) (D = +53.7 cm(-1) and E/D = 0.29 from ab initio CASSCF/NEVPT2
      calculations), thus presenting a new example of a field-induced single-ion magnet
      with transversal magnetic anisotropy. 

PMID- 24853766
TI  - Nanoways to overcome docetaxel resistance in prostate cancer.
AB  - Prostate cancer is the most common non-cutaneous malignancy in American men.
      Docetaxel is a useful chemotherapeutic agent for prostate cancer that has been
      available for over a decade, but the length of the treatment and systemic side
      effects hamper compliance. Additionally, docetaxel resistance invariably emerges,
      leading to disease relapse. Docetaxel resistance is either intrinsic or acquired
      by adopting various mechanisms that are highly associated with genetic
      alterations, decreased influx and increased efflux of drugs. Several combination
      therapies and small P-glycoprotein inhibitors have been proposed to improve the
      therapeutic potential of docetaxel in prostate cancer. Novel therapeutic
      strategies that may allow reversal of docetaxel resistance include alterations of
      enzymes, improving drug uptake and enhancement of apoptosis. In this review, we
      provide the most current docetaxel reversal approaches utilizing nanotechnology.
      Nanotechnology mediated docetaxel delivery is superior to existing therapeutic
      strategies and a more effective method to induce P-glycoprotein inhibition,
      enhance cellular uptake, maintain sustained drug release, and improve
      bioavailability. 

PMID- 24853768
TI  - NDM-1-producing Enterobacteriaceae from South Africa: moving towards endemicity?
AB  - We describe 4 patients infected with NDM-1 Enterobacter cloacae, Citrobacter
      freundii, and Serratia marcescens from South Africa that co-produced SHV-12, CTX
      M-3, and CTX-M-15 and were positive for qnrS, qnrA, aac(6')-Ib-cr, rmtF, rmtC,
      and armA. Plasmids belonged to IncN, IncA/C replicon types with ccdAB and vagC/D
      addiction factors. Local and imported cases of NDM-producing bacteria co-exist
      within South Africa. 

PMID- 24853770
TI  - Transcription activator-like effector nuclease-mediated transduction of exogenous
      gene into IL2RG locus.
AB  - X-linked severe combined immunodeficiency (SCID-X1) caused by mutations in
      interleukin 2 receptor gamma (IL2RG) gene threatens the survival of affected boys
      during the first year of life unless hematopoietic stem cell transplantation is
      provided. Although viral vector-mediated gene therapy has been successfully
      performed in patients with no HLA-matched donors, leukemia caused by vector
      mediated insertional mutagenesis has been reported in some individuals.
      Transcription activator-like effector nuclease (TALEN) is an artificial sequence
      specific endonuclease that is expected to revolutionize the precise correction of
      disease-causing mutations and eliminate the risk of insertional mutagenesis.
      Here, we report TALEN-mediated genome editing of the IL2RG locus. We transfected
      TALENs along with a targeting vector into Jurkat cells, and we confirmed the
      precise introduction of the exogenous gene into the IL2RG locus. In addition, we
      found that the length of homology arm in the targeting vector influenced the
      efficiency of TALEN-mediated homologous recombination. 

PMID- 24853771
TI  - Loss of BDNF signaling in D1R-expressing NAc neurons enhances morphine reward by
      reducing GABA inhibition.
AB  - The nucleus accumbens (NAc) has a central role in the mechanism of action of
      drugs of abuse. The major neuronal type within the NAc is the GABAergic medium
      spiny neuron (MSN), with two major subpopulations defined-termed D1-type and D2
      type MSNs-based on the predominant dopamine receptor expressed. However, very
      little is known about the contribution of altered GABAergic function in NAc MSNs
      to the neural and behavioral plasticity that contributes to the lasting actions
      of drugs of abuse. In the present study, we show that GABAergic activity is
      selectively modulated in D1-type MSNs of the NAc by signaling of brain-derived
      neurotrophic factor (BDNF) and its receptor, tyrosine receptor kinase B (TrkB),
      and that such adaptations control rewarding responses to morphine. Optical
      activation of D1-type MSNs, or the knockout of TrkB from D1-type MSNs (D1-TrkB
      KO), enhances morphine reward, effects not seen for D2-type MSNs. In addition, D1
      TrkB KO mice, but not D2-TrkB KO mice, display decreased GABAA receptor (GABAAR)
      subunit expression and reduced spontaneous inhibitory postsynaptic currents
      (sIPSCs) in D1-type, but not D2-type, MSNs in the NAc. Furthermore, we found that
      GABAAR antagonism in the NAc enhances morphine reward and that morphine exposure
      decreases TrkB expression as well as GABAergic activity in D1-type MSNs.
      Together, these data provide evidence for the enhancement of morphine reward
      through reduction of inhibitory GABAAR responses, an adaptation mediated by
      morphine-induced reduction of BDNF-TrkB signaling in D1-type MSNs. 

PMID- 24853773
TI  - C-reactive protein and lung diseases.
AB  - C-reactive protein (CRP), a member of the pentraxin family of plasma proteins, is
      one of the most distinctive acute phase reactants. In response to inflammation,
      cell damage or tissue injury, plasma level of CRP rapidly and dramatically
      increases up to 1000-fold, a phenomenon that has been used for years to monitor
      infections and many destructive/inflammatory conditions. The magnitude of CRP
      increase usually correlates with the severity of injury or inflammation and
      reflects an important physiological role of this interesting but still under
      investigated protein. It is now generally accepted that CRP is involved in host
      defense and inflammation. However, the exact function of this protein in health
      and disease remains unclear. Many studies have demonstrated that in different
      pathophysiological conditions CRP might be involved in the regulation of lung
      function and may participate in the pathogenesis of various pulmonary disorders.
      The fluctuation of CRP concentrations in both alveolar fluid and serum associated
      with different pulmonary diseases suggests its important role in lung biology.
      Discussion of the still controversial functions of CRP in lung physiology and
      diseases is the main focus of this review. 

PMID- 24853772
TI  - Importance of CRF receptor-mediated mechanisms of the bed nucleus of the stria
      terminalis in the processing of anxiety and pain.
AB  - Corticotropin-releasing factor (CRF)-mediated mechanisms in the bed nucleus of
      the stria terminalis (BNST) have a pivotal role in stress-induced anxiety and
      hyperalgesia. Although CRF is known to activate two receptor subtypes, CRF1 and
      CRF2, attempts to delineate the specific role of each subtype in modulating
      anxiety and nociception have been inconsistent. Here we test the hypothesis that
      CRF1 and CRF2 receptor activation in the anteriolateral BNST (BNSTAL) facilitates
      divergent mechanisms modulating comorbid anxiety and hyperalgesia. Microinfusions
      of the specific antagonists CP376395 and Astressin2B into the BNSTAL were used to
      investigate CRF1 and CRF2 receptor functions, respectively. We found that CRF1
      and CRF2 receptors in the BNSTAL had opposing effects on exploratory behavior in
      the elevated plus-maze, somatic mechanical threshold, and the autonomic and
      endocrine response to stress. However, CRF1 or CRF2 receptor antagonism in the
      BNSTAL revealed complementary roles in facilitating the acoustic startle and
      visceromotor reflexes. Our results suggest that the net effect of CRF1 and CRF2
      receptor activation in the BNSTAL is pathway-dependent and provides important
      insight into the CRF receptor-associated circuitry that likely underpins stress
      induced pathologies. 

PMID- 24853774
TI  - Increased expression of prostaglandin reductase 1 in hepatocellular carcinomas
      from clinical cases and experimental tumors in rats.
AB  - To identify novel tumor-associated proteins, we analyzed the protein expression
      patterns from experimental hepatocellular carcinoma (HCC) that were induced using
      hepatocarcinogenesis models in rats. Rats were subjected to two previously
      described protocols of hepatocarcinogenesis using diethylnitrosamine as a
      carcinogen: the alternative Solt-Farber (aS&F) protocol, which induces HCC within
      9 months, and Schiffer's model, which induces cirrhosis and multifocal HCC within
      18 weeks. The patterns of protein expression from tumors and normal liver tissue
      were examined by SDS-PAGE and the bands identified at 33-34 kDa were analyzed by
      mass spectrometry. The prostaglandin reductase 1 (PTGR1) showed the highest
      number of peptides, with a confidence of level >99%. The increased expression of
      PTGR1 in tumors was confirmed in these two models by Western blotting and by
      increase in alkenal/one oxidoreductase activity (25-fold higher than normal
      liver). In addition, the gene expression level of Ptgr1, as measured by qRT-PCR,
      was increased during cancer development in a time-dependent manner (200-fold
      higher than normal liver). Furthermore, PTGR1 was detected in the cytoplasm of
      neoplastic cells in rat tumors and in 12 human HCC cases by immunohistochemistry.
      These analyses were performed by comparing the expression of PTGR1 to that of two
      well-known markers of hepatocarcinoma, Glutathione S-transferase pi 1 (GSTP1) in
      rats and glypican-3 in humans. The increased expression and activity of PTGR1 in
      liver carcinogenesis encourage further research aimed at understanding the
      metabolic role of PTGR1 in HCC and its potential application for human cancer
      diagnosis and treatment.

PMID- 24853776
TI  - A level-set based approach for anterior teeth segmentation in cone beam computed
      tomography images.
AB  - Cone beam CT (CBCT) has gained popularity in dentistry for 3D imaging of the jaw
      bones and teeth due to its high resolution and relatively lower radiation
      exposure compared to multi-slice CT (MSCT). However, image segmentation of the
      tooth from CBCT is more complex than from MSCT due to lower bone signal-to-noise.
      This paper describes a level-set method to extract tooth shape from CBCT images
      of the head. We improve the variational level set framework with three novel
      energy terms: (1) dual intensity distribution models to represent the two regions
      inside and outside the tooth; (2) a robust shape prior to impose a shape
      constraint on the contour evolution; and (3) using the thickness of the tooth
      dentine wall as a constraint to avoid leakage and shrinkage problems in the
      segmentation process. The proposed method was compared with several existing
      methods and was shown to give improved segmentation accuracy. 

PMID- 24853775
TI  - The effect of compressive loading magnitude on in situ chondrocyte calcium
      signaling.
AB  - Chondrocyte metabolism is stimulated by deformation and is associated with
      structural changes in the cartilage extracellular matrix (ECM), suggesting that
      these cells are involved in maintaining tissue health and integrity. Calcium
      signaling is an initial step in chondrocyte mechanotransduction that has been
      linked to many cellular processes. Previous studies using isolated chondrocytes
      proposed loading magnitude as an important factor regulating this response.
      However, calcium signaling in the intact cartilage differs compared to isolated
      cells. The purpose of this study was to investigate the effect of loading
      magnitude on chondrocyte calcium signaling in intact cartilage. We hypothesized
      that the percentage of cells exhibiting at least one calcium signal increases
      with increasing load. Fully intact rabbit femoral condyle and patellar
      bone/cartilage samples were incubated in calcium-sensitive dyes and imaged
      continuously under compressive loads of 10-40 % strain. Calcium signaling was
      primarily associated with the dynamic loading phase and greatly increased beyond
      a threshold deformation of about 10 % nominal tissue strain. There was a trend
      toward more cells exhibiting calcium signaling as loading magnitude increased (p
      = 0.133). These results provide novel information toward identifying mechanisms
      underlying calcium-dependent signaling pathways related to cartilage homeostasis
      and possibly the onset and progression of osteoarthritis.

PMID- 24853779
TI  - A theoretical analysis of the phosphorescence efficiencies of Cu(i) complexes.
AB  - We herein report a theoretical analysis using density functional theory (DFT) and
      time-dependent DFT (TDDFT) to study the electronic structures and photophysical
      properties of mixed-ligand Cu(i) complexes. An evaluation of the non-radiative
      and radiative decay rate constants (knr and kr) is presented. It is found that
      large spin-orbit coupling (SOC) matrix elements do not necessarily result in
      large values of kr. Introducing the POP (bis[2-(diphenylphosphino)phenyl]ether)
      ligand instead of a pair of PPh3 (triphenylphosphine) ligands, it is found that
      the ether linkage plays an important role in governing the quantum efficiency of
      the studied complexes. However, the balance between hole injection and electron
      acceptance, which leads to the quantum yield of [Cu(dmp)(POP)](+) being close to
      that of [Cu(dbp)(POP)](+), is another important factor in tuning the quantum
      efficiency. A thorough understanding of the effect of the coordinating ligand on
      the photophysical behavior of a transition metal complex is desirable for the
      rational synthesis of highly phosphorescent materials. 

PMID- 24853777
TI  - Biofunctionalization of alpha-zirconium phosphate nanosheets: toward rational
      control of enzyme loading, affinities, activities and structure retention.
AB  - Controlling the properties of enzymes bound to solid surfaces in a rational
      manner is a grand challenge. Here we show that preadsorption of cationized bovine
      serum albumin (cBSA) to alpha-Zr(IV) phosphate (alpha-ZrP) nanosheets promotes
      enzyme binding in a predictable manner, and surprisingly, the enzyme binding is
      linearly proportional to the number of residues present in the enzyme or its
      volume, providing a powerful, new predictable tool. The cBSA loaded alpha-ZrP
      (denoted as bZrP) was tested for the binding of pepsin, glucose oxidase (GOX),
      tyrosinase, catalase, myoglobin and laccase where the number of residues
      increased from the lowest value of ~153 to the highest value of 2024. Loading
      depended linearly on the number of residues, rather than enzyme charge or its
      isoelectric point. No such correlation was seen for the binding of these enzymes
      to alpha-ZrP nanosheets without the preadsorption of cBSA, under similar
      conditions of pH and buffer. Enzyme binding to bZrP was supported by
      centrifugation studies, powder X-ray diffraction and scanning electron
      microscopy/energy-dispersive X-ray spectroscopy. All the bound enzymes retained
      their secondary structure and the extent of structure retention depended directly
      on the amount of cBSA preadsorbed on alpha-ZrP, prior to enzyme loading. Except
      for tyrosinase, all enzyme/bZrP biocatalysts retained their enzymatic activities
      nearly 90-100%, and biofunctionalization enhanced the loading, improved structure
      retention and supported higher enzymatic activities. This approach of using a
      chemically modified protein to serve as a glue, with a predictable
      affinity/loading of the enzymes, could be useful to rationally control enzyme
      binding for applications in advanced biocatalysis and biomedical applications. 

PMID- 24853778
TI  - Introduction: Brain malformations.
AB  - This issue of the American Journal of Medical Genetics Seminar Series Part C is
      dedicated to congenital brain malformations with a special focus on the molecular
      mechanisms underlying this fascinating, and often complex, group of developmental
      brain disorders. As with most genetic disorders, the past few years have
      witnessed a dramatic leap in our understanding of the molecular basis of these
      malformations that include both constitutional and post-zygotic (or mosaic)
      genetic aberrations. This is best exemplified by the recent identification of
      mutations within components of the PI3K-AKT-mTOR pathway in hemimegalencephaly
      and megalencephaly syndromes, and the rapidly increased identification of
      mutations within the tubulin family in a broad range of cortical and non-cortical
      brain malformations. These discoveries, particularly of the emerging
      "tubulinopathies" spectrum, have not only expanded our knowledge of these
      disorders but challenge our existing, and perhaps overly simplistic,
      classification of these malformations based on the primary neuronal stage at
      which the abnormality occurs. It is our hope that this series will facilitate a
      deeper understanding of these malformations beyond their clinical and
      neuroimaging features and syndromic associations to their molecular and pathway
      underpinnings. We believe this knowledge will most certainly be instrumental as
      we move into the era of delineating genotype-phenotype correlations and,
      ultimately, pathway-based therapies.

PMID- 24853780
TI  - Limitations in the use of surface tension and the Gibbs equation to determine
      surface excesses of cationic surfactants.
AB  - Neutron reflection (NR) and surface tension (ST) are used to show that there are
      serious limitations in applying the Gibbs equation accurately to ST data of
      cationic surfactants to obtain the limiting surface excess, Gamma(CMC), at the
      critical micelle concentration (CMC). Nonionic impurities in C12TABr and C16TABr
      have been eliminated by extensive purification to give ST - ln(concentration)
      (sigma - ln c) curves that are convex with respect to the ln c axis around the
      CMC, which is characteristic of a finite micellization width. Because NR shows
      that the surface excess often continues to increase at and above the CMC, this
      finite width makes it impossible to apply the Gibbs equation to obtain Gamma(CMC)
      without knowledge of the effect of aggregation on the activity. NR data made it
      possible to apply the integrated Gibbs equation to the ST below the onset of the
      convex region of the sigma - ln c curve and show that for C12TABr the
      micellization width causes the ST to underestimate Gamma(CMC) by 12%.
      Hexadecyltrimethylammonium (C16TA) sulfate is used to show that divalent ion
      impurities are not a significant problem. For cationic surfactants, further
      errors are associated with ST methods that rely on complete wetting. Measurements
      using ring, plate, and bubble shape analyses indicate that with ring and plate
      incomplete wetting occurs at or above the CMC and may extend to lower
      concentrations and also causes the ST-Gibbs analysis to underestimate the surface
      excess. In combination with ion association and preaggregation in cationic gemini
      surfactants, this can cause errors as large as 100% in Gamma(CMC). Comparison of
      ellipsometry and NR for C16TAX in 0.1 M KX (X = F or Cl) shows that ellipsometry
      cannot, as yet, be quantitatively modeled accurately enough for surface excess
      determination independent of NR calibration.

PMID- 24853781
TI  - Pre-existing antihypertensive treatment predicts early increase in blood pressure
      during bevacizumab therapy: the prospective AVALUE cohort study.
AB  - BACKGROUND: Antiangiogenic therapy is routinely used in a variety of cancer
      entities. Hypertension is the most common side effect of all currently available
      antiangiogenic treatments. PATIENTS AND METHODS: In this prospective
      observational clinical trial, we investigated risk factors for blood pressure
      elevation in patients exposed to an antiangiogenic agent and explored the
      correlation between hypertension and the duration of antiangiogenic treatment.
      RESULTS: In 169 patients, pre-existing antihypertensive medication was the most
      prominent risk factor associated with increased blood pressure during therapy.
      Between visits 1 and 3, the median systolic blood pressure increased by 10.85
      mmHg in patients with pre-existing hypertension receiving antihypertensive
      medication while it increased by only 2.69 mmHg in patients without hypertension.
      The median increase in diastolic pressure was 7.28 versus 0.11 mmHg in patients
      with versus without pre-existing hypertension. Increases in blood pressure
      occurred early (within 6 weeks of starting therapy). In spite of this significant
      increase in the blood pressure, no major bleeding events or other related
      complications were observed during antiangiogenic therapy. CONCLUSIONS: Pre
      existing hypertension and treatment with antihypertensive medication correlated
      with a more pronounced increase in blood pressure. Thus, intensified
      antihypertensive therapy might be warranted early during bevacizumab therapy in
      patients already receiving antihypertensive treatment.

PMID- 24853782
TI  - Single-center experience in the treatment of primary testicular lymphoma.
AB  - BACKGROUND: Primary testicular lymphoma (PTL) is a rare and highly aggressive
      extranodal non-Hodgkin's lymphoma. PATIENTS AND METHODS: We evaluated the
      clinical and histopathological features and outcomes of 10 PTL patients treated
      in the period of 2003-2013 with multimodal therapy (rituximab, CHOP
      (cyclophosphamide, doxorubicin, vincristine, and prednisone), intrathecal
      prophylaxis, irradiation of the contralateral testis) following orchiectomy.
      RESULTS: Complete remission was achieved in 8 patients after first-line therapy
      while 2 patients had disease progression. The median follow-up duration was 30
      months (range 6-110 months). Relapse occurred in 3 patients. 1 patient relapsed
      in the contralateral testis, while the other 2 patients relapsed to the skin and
      the central nervous system (CNS), respectively. The time to relapse was 2, 8, and
      9 months. Patients with disease progression and relapse received ESHAP
      (etoposide, methylprednisolone, cytarabine, and cisplatin) as salvage treatment,
      except for 1 patient who was treated with palliative radiotherapy. After second
      line therapy, only 1 patient had a short partial remission of 2 months. The
      median overall survival was 48 months, and the mean progression-free survival was
      36 months (the median was not reached). CONCLUSIONS: We evaluated 10 patients
      with PTL treated with rituximab plus CHOP, prophylactic intrathecal chemotherapy,
      and prophylactic irradiation of the contralateral testis, resulting in good
      outcome and low incidence of relapse in the contralateral testis; however, the
      benefit of intrathecal chemotherapy is not yet confirmed.

PMID- 24853783
TI  - HLA-G in testicular germ cell tumors.
AB  - BACKGROUND: HLA-G is a non-classical major histocompatibility complex class I
      molecule. HLA-G expression has been found in various types of solid and
      hematological malignancies. It is also expressed in normal testicular and
      epididymal tissue. However, expression of HLA-G in testicular germ cell tumors
      has not been extensively studied. The aim of this study was to investigate
      whether HLA-G protein is present in different components of testicular germ cell
      tumors. PATIENTS AND METHODS: 34 testicular cancer patients, for whom tumor
      tissue was available, were included in the study. Immunohistochemical staining
      was performed on tissue sections from formalin-fixed, paraffin-embedded tissue
      samples. RESULTS: 7 (20.6%) patients had positive HLA-G staining in at least 1
      component of the tumor sample. In 3 of 7 patients with intratubular germ cell
      neoplasia, staining with HLA-G was seen in this component. All of the
      choriocarcinoma components were strongly positive, and about 40% of teratoma
      components had immunopositivity. The components of seminoma and embryonal
      carcinoma, and most yolk sac tumors were negative. HLA-G immuno-positivity was
      not associated with tumor size, retroperitoneal lymph node involvement, distant
      metastasis, or relapse/refractory status. CONCLUSION: This study demonstrated
      that testicular choriocarcinoma and some teratomas express HLA-G, but not
      seminoma, embryonal carcinoma, and yolk sac tumors.

PMID- 24853784
TI  - Are changes in circulating tumor cell (CTC) count associated with the response to
      neoadjuvant chemotherapy in local advanced breast cancer? A meta-analysis.
AB  - INTRODUCTION: Circulating tumor cells (CTCs) represent a biomarker for tumor
      progression and monitoring therapeutic effects. We evaluated the association
      between the changes in CTC count and the pathological response to neoadjuvant
      chemotherapy (NCT) for local advanced breast cancer (LABC) patients. METHODS:
      PubMed, EBSCO, Web of Science, conference proceedings and key trials for the
      period 1998-2012 were searched. We used the hazard ratio (HR) to evaluate the
      variation in the number of CTCs to predict the response to NCT in LABC patients.
      All data from each study were investigated using either fixed- or random-effect
      models and were analyzed using Stata software. RESULTS: There was no between
      study heterogeneity in pathological complete response (pCR) (heterogeneity chi
      squared = 0.02 (df = 1), I(2) = 0.0%, p = 0.877). Our meta-analysis showed that
      the change (decrease or increase) in CTC number in LABC patients during NCT was
      not correlated with pCR (HR = 0.918, 95% confidence interval 0.650-1.295; p =
      0.877). CONCLUSION: The results of the current meta-analysis indicate that there
      is no association between the decrease of CTC number and pCR after NCT. According
      to our results, a decrease in the CTC count after NCT in LABC patients did not
      indicate that they had an improved response to NCT. However, more randomized
      clinical trials are needed to confirm this conclusion.

PMID- 24853785
TI  - Radiotherapy is effective for desmoid tumors (aggressive fibromatosis) - long
      term results of a German multicenter study.
AB  - BACKGROUND: Desmoids (aggressive fibromatosis) are defined as benign neoplasms of
      the connective tissue that arise from the deep muscle fascia, aponeurosis,
      tendons, and scar tissue. Recurrence rates between 40 and 80% were reported after
      surgery alone. We addressed the impact of radiation therapy (RT) in the
      management of aggressive fibromatosis. PATIENTS AND METHODS: A large literature
      review was performed, and the data was compared with the results of a multicenter
      study of the German Cooperative Group on Radiotherapy for Benign Diseases (GCG
      BD). RESULTS: This analysis included 52 patients treated with RT. 37 patients
      received postoperative RT (20 patients after R2 resection and 17 patients after
      R1 resection). 15 patients received RT alone (6 patients with inoperable primary
      tumor and 9 patients with inoperable recurrent tumor). In the case of
      postoperative RT, a median dose of 50 Gy (range 50-60 Gy) was used; for
      definitive RT, a median dose of 55 Gy (range 55-65 Gy) was used. The local
      control rate was 79% for the whole group. The median follow-up was 44 month
      (range 8-62 months). CONCLUSION: Given the large number of patients, these data
      show that RT is highly effective in the treatment of desmoid tumors. RT is an
      attractive alternative to mutilating surgery.

PMID- 24853786
TI  - Afatinib with concurrent radiotherapy in a patient with metastatic non-small cell
      lung cancer.
AB  - BACKGROUND: The combination of radiotherapy and epidermal growth factor receptor
      (EGFR) tyrosine kinase inhibitors (TKIs) such as erlotinib and gefitinib in
      patients with advanced or metastatic non-small cell lung cancer (NSCLC) has not
      been widely investigated. For afatinib, a new second generation irreversible pan
      EGFR TKI, no clinical trials in this setting have as yet been performed. CASE
      REPORT: We report a patient with a pretreated metastatic NSCLC receiving afatinib
      in combination with concomitant palliative radiotherapy to the mediastinum and
      primary lung tumor. The treatment was feasible and well tolerated. The patient
      achieved a partial response in the irradiated tumor region and the metastatic
      sites. CONCLUSION: The combination of afatinib and radiotherapy is promising and
      should be investigated further. However, because of the limited experience and
      potential side effects known for other EGFR TKIs, a decision for treatment
      outside a clinical trial has to be made very carefully, balancing the risk and
      benefit on an individual patient basis.

PMID- 24853787
TI  - Neuroendocrine tumors of the bronchopulmonary system (typical and atypical
      carcinoid tumors): current strategies in diagnosis and treatment. Conclusions of
      an expert meeting February 2011 in Weimar, Germany.
AB  - Neuroendocrine tumors (NETs; syn. carcinoid tumors) are highly or moderately
      differentiated neoplasms. They comprise a large variety of rare and heterogeneous
      tumors with an estimated incidence of 3-5/100,000/year. They can arise in
      virtually every internal organ, but mainly occur in the gastroenteropancreatic
      and bronchopulmonary systems. Around 25% of the NETs are localized in the
      bronchopulmonary system. Approximately 2% of all lung tumors are NETs. According
      to the World Health Organization (WHO) classification of lung tumors,
      bronchopulmonary NETs are subdivided into typical carcinoids (TCs) and atypical
      carcinoids (ACs). The parameter with the highest impact on NET behavior and
      prognosis is the histological classification and staging according to the
      tumor/node/metastasis (TNM) system. The diagnosis of NETs is established by
      histological examination and the immunohistochemical detection of general
      neuroendocrine markers, such as chromogranin A (CgA) and synaptophysin. Serum
      markers and the use of functional imaging techniques are important additive tools
      to establish the diagnosis of a NET. The only curative option for lung NETs is
      complete surgical resection. Beyond that, the currently available
      interdisciplinary therapeutic options are local ablation, biotherapy
      (somatostatin analogues), or chemotherapy. New therapeutic options such as
      peptide receptor radionuclide therapy (PRRT) and molecularly targeted therapies
      achieve promising results and are under further evaluation. This report is a
      consensus summary of the interdisciplinary symposium 'Neuroendocrine Tumors of
      the Lung and of the Gastroenteropancreatic System (GEP NET) - Expert Dialogue'
      held on February 25-26, 2011 in Weimar, Germany. At this conference, a panel of
      23 German experts shared their knowledge and exchanged their thoughts about
      research, diagnosis, and clinical management of NETs, whereby special attention
      was paid to NETs of the respiratory tract.

PMID- 24853788
TI  - Catheter ablation of electrical storm in a patient with left ventricular assist
      device.
AB  - Catheter ablation is an effective treatment for ventricular tachycardia (VT) in
      structural heart disease to reduce VT recurrence and implantable cardioverter
      defibrillator shocks.Current guidelines recommend ablation in patients with
      recurrent or incessant VT. In patients with left ventricular assist device
      (LVAD), VTs may be well tolerated hemodynamically and catheter ablation has been
      performed rarely, until now. We present a case of successful VT ablation in a
      patient with LVAD and electrical storm. Effective ablation after a transseptal LV
      access was achieved using electroanatomic mapping and a substrate-based approach.
      On the basis of this case, we discuss the pros and cons of VT ablation in these
      patients.

PMID- 24853789
TI  - Internet addictive behavior in adolescence: a cross-sectional study in seven
      European countries.
AB  - A cross-sectional school-based survey study (N=13,284; 53% females; mean age
      15.8+/-0.7) of 14-17-year-old adolescents was conducted in seven European
      countries (Greece, Spain, Poland, Germany, Romania, the Netherlands, and
      Iceland). The aim of the study was to investigate the prevalence of Internet
      addictive behavior (IAB) and related psychosocial characteristics among
      adolescents in the participating countries. In the study, we distinguish two
      problematic groups: adolescents with IAB, characterized by a loss of control over
      their Internet use, and adolescents "at risk for IAB," showing fewer or weaker
      symptoms of IAB. The two groups combined form a group of adolescents with
      dysfunctional Internet behavior (DIB). About 1% of adolescents exhibited IAB and
      an additional 12.7% were at risk for IAB; thus, in total, 13.9% displayed DIB.
      The prevalence of DIB was significantly higher among boys than among girls (15.2%
      vs. 12.7%, p<0.001) and varied widely between countries, from 7.9% in Iceland to
      22.8% in Spain. Frequent use of specific online activities (e.g., gambling,
      social networking, gaming) at least 6 days/week was associated with greater
      probability of displaying DIB. Multiple logistic regression analysis indicated
      that DIB was more frequent among adolescents with a lower educational level of
      the parents, earlier age at first use of the Internet, and greater use of social
      networking sites and gaming sites. Multiple linear regression analysis showed
      that externalizing (i.e., behavioral) and internalizing (i.e., emotional)
      problems were associated with the presence of DIB.

PMID- 24853791
TI  - Funding big research with small money.
AB  - This department highlights change management strategies that maybe successful in
      strategically planning and executing organizational change initiatives.With the
      goal of presenting practical approaches helpful to nurse leaders advancing
      organizational change, content includes evidence-based projects, tools,and
      resources that mobilize and sustain organizational change initiatives.In this
      article, the guest authors introduce crowd sourcing asa strategy for funding big
      research with small money.

PMID- 24853790
TI  - Cytological diagnosis of osteoblastoma of cervical spine: a case report with
      review of literature.
AB  - Osteoblastomas are rare benign but sometimes aggressive primary bone tumors (1%),
      usually seen in males in the 2nd decade. Osteoblastomas, occurring in the spine,
      constitute a medical emergency due to impending cord compression. Hence a rapid
      and simple diagnostic modality, such as fine-needle aspiration (FNA) plays an
      important role in clinical decision making. Cytological diagnosis of
      osteoblastoma is rare. We report a case of a young female patient presenting with
      a swelling in the left cervical paravertebral region. The X-ray findings were non
      diagnostic and the patient was sent for an FNA. Aspiration yielded moderately
      cellular hemorrhagic smears with plasmacytoid cells, spindle cells, and
      osteoclastic giant cells in a background of matrix material. A diagnosis favoring
      osteoblastoma was made. The CT scan findings were in agreement with the
      cytological diagnosis and the lesion was excised. Histopathological examination
      confirmed the same. We describe here, the clinical and cytological features of
      osteoblastoma with their differential diagnosis, along with review of the
      literature. FNA can be used as an important tool in the pre-operative diagnosis
      of osteoblastoma.

PMID- 24853792
TI  - The value of RN residency and fellowship programs for Magnet(r) hospitals.
AB  - This article discusses the need for accreditation of orientation transition
      programs for nurses and how these programs support Magnet criteria.

PMID- 24853793
TI  - Implementing shared governance in a patient care support industry: information
      technology leading the way.
AB  - Implementing technology in the clinical setting is not a project but rather a
      journey in transforming care delivery. As nursing leaders in healthcare and
      patient care support organizations embrace technology to drive reforms in quality
      and efficiency, growing opportunities exist to share experiences between these
      industries. This department submission describes the journey to nursing shared
      governance from the perspective of an information technology-based company
      realizing the goal of supporting patient care. 

PMID- 24853794
TI  - A conceptual model for healthcare facility design.
AB  - A conceptual model for healthcare facility design provides nurse leaders a
      framework for measuring the effect of specific or more global design features on
      patient, provider, and organizational outcomes. The model can help to explain
      relationships among variables of interest in facility design and be used to guide
      research studies or measures of change or improvement. 

PMID- 24853795
TI  - The intentional development of nurses as leaders: a proposed framework.
AB  - In their 2010 report on The Future of Nursing, the Institute of Medicine called
      for nurses to be prepared to lead in all areas of healthcare. However, the
      nursing profession lacks consensus on a framework to guide the development of
      nurses as leaders and has yet to define essential leader competencies. This
      article reviews the Army's intentional, sequential, and progressive leader
      development program that is grounded in essential leader competencies. The
      applicability of this model to nursing is discussed, and examples of how it could
      be applied are highlighted. This article proposes the use of the military
      framework as a successful model for the intentional development of nurses as
      leaders to meet the triple aims of better care for patients, better health for
      populations, and reduced costs of care through more efficient use of resources.

PMID- 24853796
TI  - The influence of nursing unit empowerment and social capital on unit
      effectiveness and nurse perceptions of patient care quality.
AB  - OBJECTIVE: This study tested a multilevel model examining the effects of work
      unit structural empowerment and social capital on perceptions of unit
      effectiveness and nurses' ratings of patient care quality. BACKGROUND: Structural
      empowerment and social capital are valuable resources for staff nurses that
      promote work effectiveness and high-quality patient care. No studies have
      examined social capital in nursing at the group level. METHODS: A cross-sectional
      survey of 525 nurses in 49 nursing units in 25 acute care hospitals in Ontario
      was conducted to test the hypothesized multilevel model using structural equation
      modeling. RESULTS: Both unit-level structural empowerment and social capital had
      significant effects on unit effectiveness (beta = .05 and beta = .29, P < .05,
      respectively). Unit-level predictors explained 87.5% of level 2 variance in
      individual nurses' ratings of patient care quality. CONCLUSIONS: This study
      provides a better understanding of how unit-level structural empowerment and
      social capital affect both unit- and individual-level outcomes.

PMID- 24853797
TI  - The role of incentives in nurses' aspirations to management roles.
AB  - OBJECTIVE: The objective of this study was to describe findings from a study
      examining nurses' perceptions of incentives for pursuing management roles.
      BACKGROUND: Upcoming retirements of nurse managers and a reported lack of
      interest in manager roles signal concerns about a leadership shortage. However,
      there is limited research on nurses' career aspirations and specifically the
      effect of perceived incentives for pursuing manager roles. METHODS: Data from a
      national, cross-sectional survey of Canadian nurses were analyzed (n = 1241)
      using multiple regression to measure the effect of incentives on nurses' career
      aspirations. RESULTS: Twenty-four percent of nurses expressed interest in
      pursuing management roles. Age, education, and incentives explained 43% of the
      variance in career aspirations. Intrinsically oriented incentives such as new
      challenges, autonomy, and the opportunity to influence others were the strongest
      predictors of aspirations to management roles. CONCLUSIONS: Ensuring an adequate
      supply of nurse managers will require proactive investment in the identification,
      recruitment, and development of nurses with leadership potential.

PMID- 24853798
TI  - Supporting nurse manager certification.
AB  - Professional certification is desirable for nursing staff and leaders to
      demonstrate high levels of knowledge and expertise. Nurse managers can be role
      models for staff by attaining certification. The organization highlighted in this
      article developed a process that included an in-house nurse manager certification
      review course resulting in increased certification rates from 33% to 50% for
      nurse managers in a 14-month period. 

PMID- 24853800
TI  - Expression of the transcription factor Egr-1 in pancreatic acinar cells following
      stimulation of cholecystokinin or Galphaq-coupled designer receptors.
AB  - BACKGOUND/AIMS: The injection of cerulein, an analogue of the pancreatic
      secretagogue cholecystokinin (CCK), induces acute pancreatitis in mice that is
      accompanied by the synthesis of the transcription factor Egr-1. The signaling
      cascade that connects cerulein stimulation with enhanced Egr-1 biosynthesis was
      analyzed. METHODS: AR42J rat pancreatic acinar cells were used as a model system
      to measure cerulein-induced Egr-1 biosynthesis. For comparison, the signaling
      cascade induced by activation of Galphaq-coupled designer receptors with the
      designer drug clozapine-N-oxide (CNO) was investigated. RESULTS: Stimulation of
      AR42J cells with cerulein induced a robust and transient biosynthesis of Egr-1.
      The signaling cascade connecting cerulein stimulation with Egr-1 gene expression
      required elevated levels of cytosolic Ca(2+) and the activation of the protein
      kinases PKC, Raf and ERK, while expression of MKP-1 prevented Egr-1 biosynthesis
      in cerulein-stimulated AR42J cells. In addition, ternary complex factors are
      required to connect cerulein stimulation with enhanced transcription of the Egr-1
      gene. Egr-1 biosynthesis induced in CNO-stimulated AR42J pancreatic acinar cells
      expressing Galphaq-coupled designer receptors required identical signaling
      molecules, although subtle differences were observed in comparison to
      cerulein/CCK receptor signaling. CONCLUSION: We propose that overstimulation of
      the canonical Galphaq-induced signaling pathway may be crucial for inducing acute
      pancreatitis.

PMID- 24853799
TI  - S-Nitrosoglutathione protects the spinal bladder: novel therapeutic approach to
      post-spinal cord injury bladder remodeling.
AB  - AIMS: Bladder and renal dysfunction are secondary events of the inflammatory
      processes induced by spinal cord injury (SCI). S-Nitrosoglutathione (GSNO), an
      endogenous nitrosylating agent is pleiotropic and has anti-inflammatory property.
      Hence, GSNO ameliorates inflammatory sequelae observed in bladder and renal
      tissues after SCI. Thus, we postulate that GSNO will improve the recovery of
      micturition dysfunction by quenching the bladder tissue inflammation associated
      with SCI. METHODS: Contusion-based mild SCI was induced in female Sprague-Dawley
      rats. Sham operated rats served as the controls. SCI rats were gavaged daily with
      GSNO (50 ug/kg) or vehicle. Bladder function was assessed by urodynamics at 2 and
      14 days following SCI. Urine protein concentration and osmolality were measured.
      Bladder and kidney tissues were analyzed by histology and immunofluorescence for
      a variety of endpoints related to inflammation. RESULTS: Two days after SCI,
      urodynamics demonstrated a hyperreflexive bladder with overflow and no clear
      micturition events. By Day 14, vehicle animals regained a semblance of a voiding
      cycle but with no definite intercontraction intervals. GSNO-treated SCI-rats
      showed nearly normal cystometrograms. Vehicle-treated SCI rats had increased
      bladder wet weight, proteinuria, and urine osmolality at Day 14, which was
      reversed by GSNO treatment. In addition, the SCI-induced increase in immune cell
      infiltration, collagen deposition, iNOS, and ICAM-1 expression and apoptosis were
      attenuated by GSNO. CONCLUSIONS: These results indicate that oral administration
      of GSNO hastens the recovery of bladder function after mild contusion-induced SCI
      through dampening the inflammation sequelae. These findings also suggest that
      GSNO-mediated redox modulation may be a novel therapeutic target for the
      treatment of mild SCI-induced renal and bladder dysfunction.

PMID- 24853801
TI  - Up-regulation of eEF1A2 promotes proliferation and inhibits apoptosis in prostate
      cancer.
AB  - BACKGROUND: eEF1A2 is a protein translation factor involved in protein synthesis,
      which possesses important function roles in cancer development. This study aims
      at investigating the expression pattern of eEF1A2 in prostate cancer and its
      potential role in prostate cancer development. METHODS: We examined the
      expression level of eEF1A2 in 30 pairs of prostate cancer tissues by using RT-PCR
      and immunohistochemical staining (IHC). Then we applied siRNA specifically
      targeting eEF1A2 to down-regulate its expression in DU-145 and PC-3 cells. Flow
      cytometer was used to explore apoptosis and Western-blot was used to detect the
      pathway proteins of apoptosis. RESULTS: Our results showed that the expression
      level of eEF1A2 in prostate cancer tissues was significantly higher compared to
      their corresponding normal tissues. Reduction of eEF1A2 expression in DU-145 and
      PC-3 cells led to a dramatic inhibition of proliferation accompanied with
      enhanced apoptosis rate. Western blot revealed that apoptosis pathway proteins
      (caspase3, BAD, BAX, PUMA) were significantly up-regulated after suppression of
      eEF1A2. More importantly, the levels of eEF1A2 and caspase3 were inversely
      correlated in prostate cancer tissues. CONCLUSION: Our data suggests that eEF1A2
      plays an important role in prostate cancer development, especially in inhibiting
      apoptosis. So eEF1A2 might serve as a potential therapeutic target in prostate
      cancer.

PMID- 24853802
TI  - Fusaric acid modulates Type Three Secretion System of Salmonella enterica serovar
      Typhimurium.
AB  - Natural small-molecule products are promising lead compounds for developing a
      generation of novel antimicrobials agents to meet the challenge of antibiotic
      resistant pathogens. To facilitate the search for novel anti-virulence agents, we
      chose a virulence factor of Type Three Secretion System (T3SS) as a drug target
      to screen candidates from a small-molecule library in our laboratory. This study
      demonstrated fusaric acid had dramatically inhibitory effects on secretion of
      Salmonella island 1 (SPI-1) effector proteins and invasion of Salmonella into
      HeLa cells. Moreover, fusaric acid had no inhibitory effects on bacterial growth
      and viability of host cells. Protein HilA is a key regulator of SPI-1 in
      Salmonella, which affects transcription of SPI-1 effectors and SPI-1 apparatus
      genes. In this study, fusaric acid (FA) did not affect secretion of SPI-1
      effectors in HilA over-expressed strain, suggesting it did not affect the
      transcription of SPI-1. In addition, fusaric acid did not affect the protein
      level of apparatus protein PrgH in SPI-1 needle complex. As a result, we proposed
      fusaric acid had an inhibitory effect on SPI-1 probably depending on its
      influence on SicA/InvF. In summary, fusaric acid is a novel inhibitor of T3SS
      with potential for further developing novel anti-virulence agents. 

PMID- 24853803
TI  - Selective stimulatory action of olfactory ensheathing glia-conditioned medium on
      oligodendroglial differentiation, with additional reference to signaling
      mechanisms.
AB  - We examined the effects of conditioned medium from olfactory ensheathing glia
      (OEGCM) on the differentiation of oligodendrocytes in mixed cultures of early
      postnatal hippocampi. Differentiation was judged from the numerical density (ND)
      of cells immunoreactive to 2'3' cyclic nucleotide 3'phosphodiesterase (CNPase)
      and O4 antibodies. NDs increased according to inverted-U dose-response curves,
      particularly for CNPase+ cells (9-fold at optimal dilution) and these changes
      were blocked by inhibitors of ERK1, p38-MAPK, and PI3K. Our results raise the
      possibility that OEG secreted factor(s) may counteract demyelination induced by
      trauma, neurodegenerative diseases, and advanced age, and should stimulate novel
      methods to deliver these factors and/or potentiating chemicals. 

PMID- 24853804
TI  - Potential anti-osteoporotic activity of low-molecular weight hyaluronan by
      attenuation of osteoclast cell differentiation and function in vitro.
AB  - Due to some severe side effects or lack of efficacy of currently used synthetic
      drugs, such as bisphosphonates (BPs), the search for new therapeutic agents that
      can more effectively prevent and treat osteoporosis (OP) has been an increasingly
      important topic of research. In this study, the low-molecular weight hyaluronan
      (LMW-HA, 50 kDa) produced by enzymatic degradation of high-molecular weight
      hyaluronan (HMW-HA, 1922 kDa) from Streptococcus zooepidemicus was evaluated in
      vitro for its anti-osteoclastogenic potentials using RAW 264.7 murine macrophage
      cells. LMW-HA (25-200 MUg/ml) dose-dependently inhibited the receptor activator
      of NF-kappaB ligand (RANKL)-induced tartrate-resistance acid phosphatase (TRAP)
      activity and the formation of multinucleated osteoclasts. Western blot analysis
      showed that LMW-HA reduced the RANKL-induced expression of tumor necrosis factor
      receptor-associated factor 6 (TRAF6), gelsolin and c-Src-proline-rich tyrosine
      kinase 2 suggesting that it could inhibit actin ring formation of osteoclast
      cells. In addition, LMW-HA inhibited the bone resorption activity of osteoclastic
      cells by dose-dependently attenuating the RANKL-induced expression of carbonic
      anhydrase II and integrin beta3. RT-PCR analysis showed that LMW-HA dose
      dependently decreased the expression of osteoclast-specific genes, such as matrix
      metalloproteinase 9 (MMP-9) and cathepsin K, suggesting that it has potential to
      inhibit the differentiation of osteoclastic cells. Taken collectively, these
      results suggested that LMW-HA (50 kDa) has significant anti-osteoporotic activity
      in vitro and may be used as a potent functional ingredient in health beneficial
      foods or as a therapeutic agent to prevent or treat OP.

PMID- 24853805
TI  - An immortalized human liver endothelial sinusoidal cell line for the study of the
      pathobiology of the liver endothelium.
AB  - BACKGROUND: The endothelium lines blood and lymph vessels and protects underlying
      tissues against external agents such as viruses, bacteria and parasites. Yet,
      microbes and particularly viruses have developed sophisticated ways to bypass the
      endothelium in order to gain access to inner organs. De novo infection of the
      liver parenchyma by many viruses and notably hepatitis viruses, is thought to
      occur through recruitment of virions on the sinusoidal endothelial surface and
      subsequent transfer to the epithelium. Furthermore, the liver endothelium
      undergoes profound changes with age and in inflammation or infection. However,
      primary human liver sinusoidal endothelial cells (LSECs) are difficult to obtain
      due to scarcity of liver resections. Relevant derived cell lines are needed in
      order to analyze in a standardized fashion the transfer of pathogens across the
      liver endothelium. By lentiviral transduction with hTERT only, we have
      immortalized human LSECs isolated from a hereditary hemorrhagic telangiectasia
      (HHT) patient and established the non-transformed cell line TRP3. TRP3 express
      mesenchymal, endothelial and liver sinusoidal markers. Functional assessment of
      TRP3 cells demonstrated a high capacity of endocytosis, tube formation and
      reactivity to immune stimulation. However, TRP3 displayed few fenestrae and
      expressed C-type lectins intracellularly. All these findings were confirmed in
      the original primary LSECs from which TRP3 were derived suggesting that these
      features were already present in the liver donor. We consider TRP3 as a model to
      investigate the functionality of the liver endothelium in hepatic inflammation in
      infection.

PMID- 24853807
TI  - Characterization of the human oncogene SCL/TAL1 interrupting locus (Stil)
      mediated Sonic hedgehog (Shh) signaling transduction in proliferating mammalian
      dopaminergic neurons.
AB  - The human oncogene SCL/TAL1 interrupting locus (Stil) is highly conserved in all
      vertebrate species. In humans, the expression of Stil is involved in cancer cell
      survival, apoptosis and proliferation. In this research, we investigated the
      roles of Stil expression in cell proliferation of mammalian dopaminergic (DA)
      PC12 cells. Stil functions through the Sonic hedgehog (Shh) signal transduction
      pathway. Co-immunoprecipitation tests revealed that STIL interacts with Shh
      downstream components, which include SUFU and GLI1. By examining the expression
      of Stil, Gli1, CyclinD2 (cell-cycle marker) and PCNA (proliferating cell nuclear
      antigen), we found that up-regulation of Stil expression (transfection with
      overexpression plasmids) increased Shh signaling transduction and PC12 cell
      proliferation, whereas down-regulation of Stil expression (by shRNA) inhibited
      Shh signaling transduction, and thereby decreased PC12 cell proliferation.
      Transient transfection of PC12 cells with Stil knockdown or overexpression
      plasmids did not affect PC12 cell neural differentiation, further indicating the
      specific roles of Stil in cell proliferation. The results from this research
      suggest that Stil may serve as a bio-marker for neurological diseases involved in
      DA neurons, such as Parkinson's disease. 

PMID- 24853806
TI  - Phosphorylation of sterol regulatory element binding protein-1a by protein kinase
      A (PKA) regulates transcriptional activity.
AB  - The counter-regulatory hormone glucagon inhibits lipogenesis via downregulation
      of sterol regulatory element binding protein 1 (SREBP-1). The effect of glucagon
      is mediated via protein kinase A (PKA). To determine if SREBP-1 is a direct
      phosphorylation target of PKA, we conducted mass spectrometry analysis of
      recombinant n-terminal SREBP-1a following PKA treatment in vitro. This analysis
      identified serines 331/332 as bona-fide phosphorylation targets of PKA. To
      determine the functional consequences of phosphorylation at these sites, we
      constructed mammalian expression vector for both nSREBP-1a and 1c isoforms in
      which the candidate PKA phosphorylation sites were mutated to active
      phosphomimetic or non-phosphorylatable amino acids. The transcriptional activity
      of SREBP was reduced by the phosphomimetic mutation of S332 of nSREBP-1a and the
      corresponding serine (S308) of nSREBP-1c. This site is a strong candidate for
      mediating the negative regulatory effect of glucagon on SREBP-1 and lipogenesis. 

PMID- 24853808
TI  - Antibody-modified lipid nanoparticles for selective delivery of siRNA to tumors
      expressing membrane-anchored form of HB-EGF.
AB  - An Fab' antibody against heparin-binding epidermal growth factor-like growth
      factor (HB-EGF) was applied to achieve advanced tumor-targeted delivery of siRNA.
      Lipid nanoparticles (LNP) encapsulating siRNA (LNP-siRNA) were prepared,
      pegylated, and surface modified with Fab' fragments of anti-HB-EGF antibody
      (alphaHB-EGF LNP-siRNA). alphaHB-EGF LNP-siRNA showed high-binding affinity to
      recombinant human HB-EGF in a Biacore assay. In addition, alphaHB-EGF LNP-siRNA
      selectively associated with cells expressing HB-EGF in vitro. Confocal
      microscopic images showed that siRNA formulated in alphaHB-EGF LNP-siRNA was
      efficiently internalized into MDA-MB-231 human breast cancer cells, on which HB
      EGF is highly expressed. In addition, siRNA encapsulated in alphaHB-EGF LNP
      induced obvious suppression of both target mRNA and protein levels in MDA-MB-231
      cells. These results indicate that alphaHB-EGF LNP have excellent potential to
      deliver siRNA to target cancer cells, resulting in effective gene silencing. 

PMID- 24853809
TI  - Nursing home patients with diabetes: prevalence, drug treatment and glycemic
      control.
AB  - AIMS: Determine prevalence of diabetes, and describe use of blood glucose
      lowering (BGL) drugs and glycemic control in Norwegian nursing homes. METHODS: In
      this cross-sectional study we collected details of BGL drugs, capillary blood
      glucose measurements (CBGM) in the last four weeks and HbA1c measurements in the
      last 12 months from the medical records of patients with diabetes, within a
      population of 742 long-term care patients from 19 randomly selected nursing homes
      in Western Norway. Descriptive statistics were applied, and Pearson's chi-squared
      (P<=0.05) or non-overlapping 95% confidence intervals were interpreted as
      significant effects. RESULTS: 116 patients (16%) had diabetes, 100 of these gave
      informed consent and medical data were available. BGL treatment was as follows:
      (1) insulin only (32%), (2) insulin and oral antidiabetics (OADs) (15%), (3) OADs
      only (27%) and (4) no drugs (26%). Patients with cognitive impairment were less
      likely to receive medical treatment (P=0.04). CBGM and HbA1c measurements were
      performed for 73% and 77% of patients, respectively. Mean HbA1c was 7.3% (57
      mmol/mol), 46% of patients had an HbA1c <7.0% (53 mmol/mol), and CBGM consistent
      with risk of hypoglycemia was found for 60% of these patients. CONCLUSIONS:
      Prevalence of diabetes and BGL treatment in Norwegian nursing homes is comparable
      to other European countries. Although special care seems to be taken when
      choosing treatment for patients with cognitive impairment, there are signs of
      overtreatment in the population as a whole. The strict glycemic control unveiled
      may negatively affect these frail patients' quality of life and increase the risk
      of early death.

PMID- 24853816
TI  - DNA-mediated oxidation of p53.
AB  - Transcription factor p53 is the most commonly altered gene in human cancer. As a
      redox-active protein in direct contact with DNA, p53 can directly sense oxidative
      stress through DNA-mediated charge transport. Electron hole transport occurs over
      long distances through the pi-stacked bases and leads to the oxidative
      dissociation of p53. The extent of protein dissociation depends upon the redox
      potential of the DNA in direct contact with each p53 monomer. The DNA sequence
      dependence of p53 oxidative dissociation was examined by electrophoretic mobility
      shift assays using oligonucleotides containing both synthetic and human p53
      consensus sequences with an appended photooxidant, anthraquinone. Greater p53
      dissociation is observed from sequences containing low-redox potential purine
      regions, particularly guanine triplets. Using denaturing polyacrylamide gel
      electrophoresis of irradiated anthraquinone-modified DNA, the DNA damage sites
      corresponding to sites of preferred electron hole localization were determined.
      The resulting DNA damage preferentially localizes to guanine doublets and
      triplets. Oxidative DNA damage is inhibited in the presence of p53, but only at
      sites in direct contact with p53. From these data, predictions about the
      sensitivity of human p53-binding sites to oxidative stress as well as possible
      biological implications have been made. On the basis of our data, the guanine
      pattern within the purine region of each p53-binding site determines the response
      of p53 to DNA oxidation, yielding for some sequences the oxidative dissociation
      of p53 from a distance and thereby providing another potential role for DNA
      charge transport chemistry within the cell. 

PMID- 24853817
TI  - LiFePO4 nanoparticles encapsulated in graphene nanoshells for high-performance
      lithium-ion battery cathodes.
AB  - LiFePO4 encapsulated in graphene nanoshells (LiFePO4@GNS) nanoparticles were
      synthesized by solid state reaction between graphene-coated Fe nanoparticles and
      LiH2PO4. The resulting nanocomposite was demonstrated to be a superior lithium
      ion battery cathode with improved cycle and rate performances. 

PMID- 24853818
TI  - Measuring microangiopathy abnormalities in systemic sclerosis patients: the role
      of capillaroscopy-based scoring models.
AB  - Capillaroscopy is a noninvasive imaging technique for the in vivo study of
      microcirculation. The role of a qualitative evaluation of capillaroscopy in the
      assessment of Raynaud's phenomenon secondary to scleroderma spectrum disorder,
      particularly systemic sclerosis (SSc), is well defined. The usefulness of
      capillaroscopy in the follow-up of SSc patients and the possible prognostic role
      for the appearance of typical SSc vascular and visceral involvement, namely,
      digital ulcers, pulmonary arterial hypertension, and mortality, is suggested by
      many authors but still under debate. In this regard, and for a reliable and
      repeatable longitudinal evaluation of SSc microangiopathy, a quantitative
      analysis should be required. In this review, we describe the current
      classifications proposed to define the SSc microvascular involvement and the
      scoring methods suggested for a semiquantitative and quantitative analysis of
      microangiopathy and its correlation with clinical manifestations of disease.

PMID- 24853819
TI  - Measuring cervical strain with tissue Doppler imaging depending on the shape and
      placement of the region of interest and its correlation with cervical consistency
      index.
AB  - OBJECTIVES: We want to evaluate tissue Doppler imaging (TDI) for measuring
      cervical strain. We compare three different methods for measuring strain
      depending on the region of interest (ROI) placement and evaluate patient
      discomfort. We correlate the strain measured through TDI with cervical
      consistency index (CCI), cervical length and width of both cervical lips. STUDY
      DESIGN: This is a prospective study in 30 singleton primigravida pregnancies
      without obstetrical risks between 40+0 and 41+3 weeks of gestation. The CCI was
      calculated according to Parra-Saavedra et al. We tested three methods of
      measuring cervical elasticity depending on shape and location of ROIs. RESULTS:
      The CCI ranged between 36.4% and 71.9% with an average of 50.78%. The CCI shows
      negative correlation with strain and no correlation with cervical length or with
      the width of either cervical lip. The strain measurements regardless of tested
      method were reproducible and independent on cervical length. The average strain
      was higher in outer cervical regions. The ROIs placed on the anterior lip had
      higher reproducibility than those placed on the posterior lip. The average score
      for patient discomfort during examination was 3.7/10. CONCLUSION: The strain
      depends on the size and location of ROIs. The circular ROIs with diameter equal
      to the width of the cervical lip are recommended. There is a correlation between
      CCI and TDI. The cervix shows heterogeneous consistency with increased stiffness
      from the outer to the inner sections. The TDI seems to be an easy to learn,
      quickly to perform, acceptable and reproducible method for measuring cervical
      elasticity. There is room for optimization and refinement of measuring methods
      before being tested for clinical significance.

PMID- 24853820
TI  - Author's response to "Avoiding radiation in management of post-partum hemorrhage:
      CT angiography is not a good idea".

PMID- 24853822
TI  - New perspectives in neuropsychology.

PMID- 24853823
TI  - A lifetime in neuropsychology--perspectives on an era.

PMID- 24853821
TI  - HIV-1 envelope gp41 broadly neutralizing antibodies: hurdles for vaccine
      development.

PMID- 24853825
TI  - Exploring health promotion practitioners' experiences of moral distress in Canada
      and Australia.
AB  - This article introduces moral distress - the experience of painful feelings due
      to institutional constraints on personal moral action - as a significant issue
      for the international health promotion workforce. Our exploratory study of
      practitioners' experiences of health promotion in Australia and Canada during
      2009-2010 indicated that practitioners who work in upstream policy- and systems
      level health promotion are affected by experiences of moral distress. Health
      promotion practitioners at all levels of the health promotion continuum also
      described themselves as being engaged in a minority practice within a larger
      dominant system that does not always value health promotion. We argue that health
      promotion practitioners are vulnerable to moral distress due to the values-driven
      and political nature of the practice, the emphasis on systems change and the
      inherent complexity and diversity of the practice. This vulnerability to moral
      distress poses significant challenges to both workers and organisations and the
      communities they seek to benefit. We propose that further research should be
      undertaken to fully identify the causes and symptoms of moral distress in health
      promotion. Extensive existing research on moral distress in nursing provides
      ample resources to conduct such research. 

PMID- 24853824
TI  - Longitudinal change in working memory as a function of APOE genotype in midlife
      and old age.
AB  - Previous investigations into whether the APOE-epsilon4 allele exerts cognitive
      effects at midlife have been inconclusive. We have advanced a "cognitive
      phenotype" hypothesis arguing that the epsilon4 allele of the apolipoprotein E
      gene (APOE) is associated with lower efficiency of neuronal plasticity thereby
      resulting in poorer cognitive performance independently of the pathology of
      Alzheimer's disease (Greenwood et al., ). This hypothesis is best tested at
      midlife, prior to the neuron loss associated with AD diagnosis. This hypothesis
      predicts that the epsilon4 allele would alter cognition regardless of age through
      plasticity mechanisms, but would not induce longitudinal decline in midlife. The
      alternative "prodrome" hypothesis predicts that the APOE-epsilon4 allele would be
      associated with longitudinal cognitive decline as early as midlife due to
      prodromal effects of AD. We tested these hypotheses with a working memory task in
      a large cross-sectional sample of cognitively screened APOE-epsilon4 carriers and
      non-carriers and also in a small longitudinal sample over 3 years. The sample was
      divided into middle-aged (mean age 50, range 40-59) and older (mean age 69, range
      60-84) individuals. Cross-sectionally, we observed that older, but not middle
      aged, APOE-epsilon4 carriers had lower accuracy than epsilon4 non-carriers,
      mainly under the hardest discrimination condition. Longitudinally, we observed
      increases in accuracy in middle-aged APOE-epsilon4 carriers, suggesting a
      cognitive phenotype that includes ability to benefit from experience. We observed
      a longitudinal decrease in older APOE-epsilon4 carriers, suggesting an AD
      prodrome.

PMID- 24853826
TI  - Metabolomics study of hepatocellular carcinoma: discovery and validation of serum
      potential biomarkers by using capillary electrophoresis-mass spectrometry.
AB  - Hepatocellular carcinoma (HCC) is one of the most lethal malignancies. The lack
      of effective screening methods for early diagnosis has been a longstanding
      bottleneck to improve the survival rate. In the present study, a capillary
      electrophoresis-time-of-flight mass spectrometry (CE-TOF/MS)-based metabolomics
      method was employed to discover novel biomarkers for HCC. A total of 183 human
      serum specimens (77 sera in discovery set and 106 sera in external validation
      set) were enrolled in this study, and a "serum biomarker model" including
      tryptophan, glutamine, and 2-hydroxybutyric acid was finally established based on
      the comprehensive screening and validation workflow. This model was evaluated as
      an effective tool in that area under the receiver operating characteristic curve
      reached 0.969 in the discovery set and 0.99 in the validation set for diagnosing
      HCC from non-HCC (health and cirrhosis). Furthermore, this model enabled the
      discrimination of small HCC from precancer cirrhosis with an AUC of 0.976,
      highlighting the potential of early diagnosis. The biomarker model is effective
      for those a-fetoprotein (AFP) false-negative and false-postive subjects,
      indicating the complementary function to conventional tumor marker AFP. This
      study demonstrates the promising potential of CE-MS-based metabolomics approach
      in finding biomarkers for disease diagnosis and providing special insights into
      tumor metabolism. 

PMID- 24853827
TI  - Prophylactic treatment of retinal breaks--a systematic review.
AB  - Prophylactic treatment of retinal breaks has been examined in several studies and
      reviews, but so far, no studies have successfully applied a systematic approach.
      In the present systematic review, we examined the need of follow-up after
      posterior vitreous detachment (PVD) - diagnosed by slit-lamp biomicroscopy or
      Goldmann 3-mirror examination - with regard to retinal breaks as well as the
      indication of prophylactic treatment in asymptomatic and symptomatic breaks. A
      total of 2941 publications were identified with PubMed and Medline searches. Two
      manual search strategies were used for papers in English published before 2012.
      Four levels of screening identified 13 studies suitable for inclusion in this
      systematic review. No meta-analysis was conducted as no data suitable for
      statistical analysis were identified. In total, the initial examination after
      symptomatic PVD identified 85-95% of subsequent retinal breaks. Additional
      retinal breaks were only revealed at follow-up in patients where a full retinal
      examination was compromised at presentation by, for example, vitreous
      haemorrhage. Asymptomatic and symptomatic retinal breaks progressed to
      rhegmatogenous retinal detachment (RRD) in 0-13.8% and 35-47% of cases,
      respectively. The cumulated incidence of RRD despite prophylactic treatment was
      2.1-8.8%. The findings in this review suggest that follow-up after symptomatic
      PVD is only necessary in cases of incomplete retinal examination at presentation.
      Prophylactic treatment of symptomatic retinal breaks must be considered, whereas
      no unequivocal conclusion could be reached with regard to prophylactic treatment
      of asymptomatic retinal breaks.

PMID- 24853828
TI  - Arterial stiffening provides sufficient explanation for primary hypertension.
AB  - Hypertension is one of the most common age-related chronic disorders, and by
      predisposing individuals for heart failure, stroke, and kidney disease, it is a
      major source of morbidity and mortality. Its etiology remains enigmatic despite
      intense research efforts over many decades. By use of empirically well
      constrained computer models describing the coupled function of the baroreceptor
      reflex and mechanics of the circulatory system, we demonstrate quantitatively
      that arterial stiffening seems sufficient to explain age-related emergence of
      hypertension. Specifically, the empirically observed chronic changes in pulse
      pressure with age and the impaired capacity of hypertensive individuals to
      regulate short-term changes in blood pressure arise as emergent properties of the
      integrated system. The results are consistent with available experimental data
      from chemical and surgical manipulation of the cardio-vascular system. In
      contrast to widely held opinions, the results suggest that primary hypertension
      can be attributed to a mechanogenic etiology without challenging current
      conceptions of renal and sympathetic nervous system function. 

PMID- 24853829
TI  - Serial clopidogrel dose adjustment after platelet function testing improves
      outcome of acute coronary syndrome patients undergoing percutaneous coronary
      intervention with high on-treatment platelet reactivity.
AB  - High on-treatment platelet reactivity (HTPR) on clopidogrel correlates with
      adverse outcomes in patients treated with percutaneous coronary intervention
      (PCI). Whether HTPR is a modifiable risk factor for future events is not clear.
      We evaluated the effect of serial clopidogrel dose adjustment based on platelet
      function testing (PFT) during 12 months of dual antiplatelet therapy (DAPT) using
      Multiplate) analyzer in patients with HTPR after PCI in acute coronary syndrome
      on clinical outcome. Eighty-seven patients were randomized to interventional (n =
      43) and control group (n = 44). Blood samples for PFT were drawn at day 1, 2, 3,
      7, 30 and at month 2, 3, 6, 9 and 12. Clopidogrel dose was modified at each point
      of PFT in the interventional group with patients taking up to two additional 600
      mg loading doses and a range of 75-300 mg maintenance dose to achieve and
      maintain optimal platelet reactivity (19-46 U). The incidence of the primary
      endpoint (composite of cardiovascular death, non-fatal myocardial infarction,
      target vessel revascularization and ischemic stroke) was significantly higher in
      the control group (36.3 vs. 16.2%; p = 0.034). There were no differences in total
      bleeding events (6.8 vs. 4.6%, p = ns). Patients in the interventional group
      maintained better P2Y12 inhibition during follow-up. We hypothesize that
      targeting the therapeutic window of platelet reactivity continuously throughout
      DAPT by dose adjustment of P2Y12 inhibitor may lead to better platelet reactivity
      control, and thus reduce the rate of ischemic complications in this high risk
      group of patients.

PMID- 24853831
TI  - [Abusive head trauma: report of a case].
AB  - The abusive head trauma is a form of child abuse. The most frequent injuries are
      intracranial lesions, such as subdural hematoma, as well as retinal hemorrhages,
      usually without other external injuries. Due to its complexity, this problem
      requires a multidisciplinary medical team, where the role of the radiologist is
      important, since there are multiple diagnostic methods that are complementary in
      order to arrive at the correct diagnosis. 

PMID- 24853830
TI  - Incidence and prognostic significance of myocardial late gadolinium enhancement
      in patients with sarcoidosis without cardiac manifestation.
AB  - BACKGROUND: Cardiac death is the leading cause of mortality associated with
      sarcoidosis in Japan. However, the involvement of sarcoidosis infiltration often
      remains undetected. Recently, late gadolinium enhancement with cardiovascular MRI
      (LGE-CMR) imaging has been introduced for the detection of myocardial
      infiltrative disease, as it enables the detection of even minor myocardial
      damage. We investigated the incidence and prognostic value of LGE-CMR in patients
      with extracardiac sarcoidosis without cardiac manifestations. METHODS: Sixty-one
      consecutive patients who met the histologic and clinical criteria for
      sarcoidosis, and who did not have signs or symptoms of cardiovascular
      involvement, were prospectively recruited. LGE-CMR was performed at the time of
      enrollment, and patients were classified into positive or negative late
      gadolinium enhancement groups based on the findings. The study end point was a
      composite of all-cause death, symptomatic arrhythmia, and heart failure
      necessitating admission. RESULTS: Patients were predominantly middle aged (57 +/-
      15 years) and female (66%), and most had stable disease activity that did not
      require treatment with immunosuppressants. LGE-CMR detected cardiac involvement
      in eight patients (13%). Interventricular septal thinning detected by
      echocardiography was an independent predictor of LGE-CMR-detected cardiac
      involvement. During the follow-up period of 50 +/- 12 months, no significant
      difference in adverse events was noted between patients in the LGE-CMR-positive
      and LGE-CMR-negative groups. CONCLUSIONS: LGE-CMR detected cardiac involvement in
      13% of patients with sarcoidosis without cardiac manifestation, but both patients
      with and without LGE had relatively low event rates. TRIAL REGISTRY: Japan
      Primary Registries Network; No.: UMIN000001549; URL: www.umin.ac.jp.

PMID- 24853832
TI  - Recognizing emotional speech in Persian: a validated database of Persian
      emotional speech (Persian ESD).
AB  - Research on emotional speech often requires valid stimuli for assessing perceived
      emotion through prosody and lexical content. To date, no comprehensive emotional
      speech database for Persian is officially available. The present article reports
      the process of designing, compiling, and evaluating a comprehensive emotional
      speech database for colloquial Persian. The database contains a set of 90
      validated novel Persian sentences classified in five basic emotional categories
      (anger, disgust, fear, happiness, and sadness), as well as a neutral category.
      These sentences were validated in two experiments by a group of 1,126 native
      Persian speakers. The sentences were articulated by two native Persian speakers
      (one male, one female) in three conditions: (1) congruent (emotional lexical
      content articulated in a congruent emotional voice), (2) incongruent (neutral
      sentences articulated in an emotional voice), and (3) baseline (all emotional and
      neutral sentences articulated in neutral voice). The speech materials comprise
      about 470 sentences. The validity of the database was evaluated by a group of 34
      native speakers in a perception test. Utterances recognized better than five
      times chance performance (71.4 %) were regarded as valid portrayals of the target
      emotions. Acoustic analysis of the valid emotional utterances revealed
      differences in pitch, intensity, and duration, attributes that may help listeners
      to correctly classify the intended emotion. The database is designed to be used
      as a reliable material source (for both text and speech) in future cross-cultural
      or cross-linguistic studies of emotional speech, and it is available for academic
      research purposes free of charge. To access the database, please contact the
      first author. 

PMID- 24853833
TI  - Improved random-starting method for the EM algorithm for finite mixtures of
      regressions.
AB  - Two methods for generating random starting values for the expectation
      maximization (EM) algorithm are compared in terms of yielding maximum likelihood
      parameter estimates in finite mixtures of regressions. One of these methods is
      ubiquitous in applications of finite mixture regression, whereas the other method
      is an alternative that appears not to have been used so far. The two methods are
      compared in two simulation studies and on an illustrative data set. The results
      show that the alternative method yields solutions with likelihood values at least
      as high as, and often higher than, those returned by the standard method.
      Moreover, analyses of the illustrative data set show that the results obtained by
      the two methods may differ considerably with regard to some of the substantive
      conclusions. The results reported in this article indicate that in applications
      of finite mixture regression, consideration should be given to the type of
      mechanism chosen to generate random starting values for the EM algorithm. In
      order to facilitate the use of the proposed alternative method, an R function
      implementing the approach is provided in the Appendix of the article. 

PMID- 24853834
TI  - Control of the number of cell division rounds in distinct tissues during ascidian
      embryogenesis.
AB  - An important question in developmental biology is how the number of cells
      constituting the body is regulated during development. After termination of cell
      divisions, cells enter the postmitotic phase, but the mechanisms determining the
      timing of final cell division remain unclear. In ascidians, the egg develops into
      a tadpole larva consisting of a relatively small number of cells (approximately
      2800), indicating that embryonic cells divide 11.5 times on average after
      fertilization, although the number of cell division rounds differs among tissues.
      This article discusses the possible mechanisms that control the timing of the
      final cell division: these include (i) the analog and digital clock models, in
      which the elapsed time and number of cell division cycles are measured after
      fertilization, respectively, and (ii) the analog and digital timer models, in
      which the elapsed time and number of cell divisions are measured after cell fate
      specification, respectively. In notochord and muscle cells of ascidian embryos,
      cell division termination involves cell fate specification by inductive FGF
      signaling, followed by activation of the tissue-specific key transcription
      factors, Brachyury and Tbx6, which then induce gene expression of an effector,
      Cdk inhibitor. The present evidence suggests that these timing mechanisms
      comprise two functional phases: (i) an analog timer, which is mediated by
      accumulation of Cdk inhibitor protein after cell fate specification, and (ii) a
      timekeeper, which confines the timing, when the above timer is triggered by
      Brachyury and Tbx6, to the appropriate stage. 

PMID- 24853835
TI  - Puerperal retroperitoneal abscess caused by Clostridium difficile: case report
      and review of the literature.
AB  - BACKGROUND: Retroperitoneal infection can be lethal. Optimal management is still
      elusive to describe because of the small number of case reports. We presented
      here a case of retroperitoneal abscess caused by Clostridium difficile arising in
      the puerperal period. METHODS: Case report and review of recent English-language
      literature. RESULTS: The patient presented with surgical incision dehiscence. A
      gas-forming fluid collection was discovered in the pelvic retroperitoneal fascia
      by computed tomography, but the patient did not show marked symptoms of sepsis.
      Emergency laparotomy drainage and debridement were performed. Clostridium
      difficile was isolated, and she was treated with a three-week course of
      vancomycin. The patient recovered without major morbidity. Recent case reports
      describe variation in the course of the disease and management options for
      puerperal retroperitoneal infection. CONCLUSION: Puerperal retroperitoneal
      abscess caused by C. difficile can present with minimal symptoms. Prompt
      recognition, early surgical intervention, and optimal use of antibiotics can
      reduce morbidity and prevent death.

PMID- 24853836
TI  - Fundoplication versus medical management of gastroesophageal reflux disease:
      systematic review and meta-analysis.

PMID- 24853837
TI  - Laparoscopic versus open gastric resection for larger than 5 cm primary gastric
      gastrointestinal stromal tumors (GIST): a size-matched comparison.
AB  - BACKGROUND: Laparoscopic resection of gastric gastrointestinal stromal tumors
      (GISTs) appears technically feasible and associated with favorable outcomes.
      Tumor size plays an important role in surgical approach, with laparotomy tending
      to be used to treat larger tumors. This study evaluated the technical
      feasibility, safety, and oncologic efficacy of laparoscopic surgery for GISTs >=5
      cm in diameter. METHODS: One hundred forty patients who underwent resection of
      primary gastric GIST at our institution from January 2007 to December 2012 were
      identified. Twenty-three patients with tumor larger than 5 cm in diameter treated
      by laparoscopic resection and were randomly matched (1:1) by tumor size (+/-1 cm)
      to patients with open resection. Clinical and pathologic variables and surgical
      outcomes for each surgical type were identified and compared. RESULTS: There were
      no significant differences in clinicopathologic characteristics between the two
      groups. Laparoscopic group was superior to open group in operation time, blood
      loss, time to ground activities, time to first flatus, times to liquid diet, and
      postoperative stay (P < 0.05). Number of transfusions and time to semi-liquid
      diet, however, did not differ between groups. There was no operative mortality,
      and the postoperative complications were similar. Fifteen patients in the
      laparoscopic group and 17 patients in the open group received adjuvant treatment
      with imatinib. Recurrence or metastasis occurred in eight cases (three in the
      laparoscopic group and five in the open group). No significant difference in long
      term disease-free survival was found between the two groups (P > 0.05).
      CONCLUSION: When performed by experienced surgeons, laparoscopic resection for
      gastric GISTs larger than 5 cm is a safe and effective minimally invasive
      surgery.

PMID- 24853838
TI  - The effects of viewing axis on laparoscopic performance: a comparison of non
      expert and expert laparoscopic surgeons.
AB  - BACKGROUND: While the ideal relationship of telescope viewing axis and instrument
      working axis in laparoscopic surgery is co-axial, it is often necessary to
      deviate view of the surgical field from the direction of working instruments with
      potentially negative implications to performance. The objectives of this study
      are to (1) characterize performance effects of working progressively further off
      telescope viewing axis and (2) compare the ability of expert laparoscopic
      surgeons and non-expert surgeons to compensate for the psychomotor problems
      imposed by off-axis viewing. METHODS: Subjects included Baystate Medical Center
      surgical residents between PGY 1 and PGY 5 training years and attending surgeons.
      Expert subjects (>250 basic and >50 advanced laparoscopic cases, N = 6) and non
      expert subjects (N = 11) performed the FLS peg transfer task in a box trainer
      configured to accept a laparoscope inserted at 0 degrees , 45 degrees , 90
      degrees , 135 degrees , and 180 degrees  viewing angles relative to axis of
      working instruments. Performance measures included time to task completion
      (seconds), errors (# dropped objects), and percent completed transfers.
      Statistical analysis took into account repeated measures within each subject for
      each performance measure. Trends were assessed using linear contrasts for trend
      (p-trend). Differences between experts and non-experts were evaluated using an
      interaction term (p-interaction). RESULTS: Overall there was increased time to
      completion (p < 0.001), increased number of dropped pegs (p < 0.001), and
      decreased percentage of completed transfers (<0.001) as the viewing axis relative
      to working instruments increased from 0 degrees  to 180 degrees . Overall, expert
      laparoscopic surgeons demonstrated significantly shorter time to completion (p <
      0.0027), fewer dropped pegs (p < 0.001), and higher percentage of completed peg
      transfers (p < 0.0001) compared to non-expert surgeons. CONCLUSIONS: Surgeon
      performance degrades as viewing axis increases from 0 degrees  to 180 degrees 
      relative to working instruments. Expert laparoscopic surgeons perform better than
      non-expert surgeons when working off the laparoscope viewing axis.

PMID- 24853839
TI  - Minimally invasive RAMPS in well-selected left-sided pancreatic cancer within
      Yonsei criteria: long-term (>median 3 years) oncologic outcomes.
AB  - BACKGROUND: Although minimally invasive techniques for distal pancreatectomy with
      or without splenectomy have been regarded as a feasible and safe treatment option
      for benign and borderline malignant lesions of the pancreas, the management of
      left-sided pancreatic cancer remains controversial. METHODS: From June 2007 to
      November 2010, 12 patients underwent laparoscopic or robotic radical antegrade
      modular pancreatosplenectomy (RAMPS) for well-selected left-sided pancreatic
      cancer. The Yonsei criteria for patient selection included the following
      conditions: (1) tumor confined to the pancreas, (2) intact fascial layer between
      the distal pancreas and the left adrenal gland and kidney, and (3) tumor located
      more than 1-2 cm from the celiac axis. We compared the clinicopathologic factors
      and oncologic outcomes of the minimally invasive surgery (MIS) and the
      conventional open surgery groups for treating left-sided pancreatic cancer.
      RESULTS: In the MIS group, the mean tumor size was 2.75 +/- 1.32 cm, and the mean
      number of retrieved lymph nodes was 10.5 +/- 7.14. The resection margins were
      confirmed to be negative for malignancy in all patients. The MIS group and open
      group (n = 78) were statistically different in terms of tumor size (2.8 +/- 1.3
      vs. 3.5 +/- 1.9 cm, p = 0.05) and length of hospital stay (12.3 +/- 6.8 vs. 22.4
      +/- 21.6 days, p = 0.002). On survival analysis, the MIS group had longer disease
      free survival (DFS) and overall survival (OS) than the open group (DFS: 47.6 vs.
      24.7 months, p = 0.027; OS: 60.0 vs. 30.7 months, p = 0.046). In order to
      overcome the heterogeneity of subjects between the MIS and the open group, we
      performed statically matched comparisons using the propensity score analysis and
      then divided the open group into two subgroups according to the Yonsei criteria.
      There were no significant differences in median overall survival between the MIS
      group and the open group that met the Yonsei criteria (60.00 vs. 60.72 months, p
      = 0.616). CONCLUSIONS: Minimally invasive RAMPS is not only technically feasible
      but also oncologically safe in cases of well-selected left-sided pancreatic
      cancer. Our selection criteria for minimally invasive RAMPS needs to be further
      validated based on additional large-volume studies.

PMID- 24853840
TI  - Effects of CO2 pneumoperitoneum on the expression of thymidine kinase 1 and Ki67
      in colorectal carcinoma cells.
AB  - BACKGROUND: To investigate thymidine kinase 1(TK-1) and Ki67 expression levels of
      human colorectal carcinoma cells line SW480 after exposure to a simulated
      laparoscopic carbon dioxide (CO2) pneumoperitoneum environment at different
      pressures and lengths of exposure time. METHODS: The effects of the simulated
      laparoscopic CO2 pneumoperitoneum environment at different CO2 pressures (6, 9,
      12, and 15 mmHg) and exposure times (2 and 4 h) on TK-1 and Ki67 of SW480 cells
      were assessed by flow cytometry and reverse transcription (RT-PCR). Cells
      cultured in a standard environment were used as the control group (at 37  degrees
      C, 5% CO2). RESULTS: In this study, TK-1 and Ki67 in SW480 cells tended to
      decrease with the increase of CO2 pressure and exposure time. Significantly lower
      expression levels were observed at 0 and 24 h of culture after exposure to both
      at 12 and 15 mmHg, as compared with the control group at 6 and 9 mmHg (p < 0.05).
      The expression of TK-1 and Ki67 levels increased up to a plateau of the control
      group after 48 and 72 h (p > 0.05). With the CO2 pneumoperitoneum exposure time
      prolonging, the expression of TK-1 and Ki67 levels in 12 or 15 mmHg was lower
      than in 2 h (p < 0.05). In the same exposure time, the transcription level of TK
      1 and Ki67 decreased significantly in 12 and 15 mmHg CO2 pneumoperitoneum groups
      (p < 0.05) and returned to the basal level of control group after being
      cultivated for 48 h (p > 0.05). In the same pressure, the difference of TK-1 mRNA
      between the groups of 2 and 4 h was also significant. CONCLUSION: The expression
      levels of TK-1 and Ki67 were suppressed temporarily after the continuous CO2
      insufflation in higher pressure (at 12 and 15 mmHg). The higher the pressure of
      CO2 insufflation, the more the inhibiting effects of TK-1 and Ki67 will be. The
      longer the time of CO2 insufflation, the more significantly their expression
      decreased.

PMID- 24853841
TI  - Single-port laparoscopic colorectal resections in obese patients are as safe and
      effective as conventional laparoscopy.
AB  - BACKGROUND: Obese patients pose additional operative technical difficulties, and
      it is unclear if the outcomes of single-port colorectal surgery are equivalent to
      those of conventional laparoscopy in such patients. The aim of this study was to
      compare perioperative variables and short-term outcomes of single-port versus
      conventional laparoscopy in obese patients undergoing colorectal surgery.
      PATIENTS AND METHODS: Obese patients (BMI >= 30 kg/m(2)) undergoing single-port
      laparoscopic colorectal resections between March 2009 and September 2012 were
      case matched 1:1 with obese counterparts undergoing conventional (multi-port)
      laparoscopic surgery based on diagnosis and operation type. RESULTS: Thirty-seven
      patients who underwent single-port surgery were matched with 37 conventional
      laparoscopic counterparts. Male gender predominated in the single-port group (26
      vs 15, p = 0.02). The number of patients with a history of previous abdominal
      operations (17 vs 13, p = 0.48) and ASA score (3 vs 2, p = 0.6) were similar
      between the groups. No differences were observed with respect to conversion rate
      (2 vs 5, p = 0.43), operative time (146 vs 150 min, p = 0.48), estimated blood
      loss (159 vs 183 ml, p = 0.99), time to first flatus (3 vs 3 days, p = 0.91),
      time to first bowel movement (3 vs 4 days, p = 0.62), length of hospital stay (7
      vs 6 days, p = 0.37), or reoperation (2 vs 1, p > 0.99), and readmission rates (2
      vs 2, p > 0.99). There were no deaths. CONCLUSION: For obese patients undergoing
      colorectal resections, single-port laparoscopy appears to be as safe and
      effective as conventional laparoscopy.

PMID- 24853842
TI  - Preoperative re-endoscopy in colorectal cancer patients: an institutional
      experience and analysis of influencing factors.
AB  - BACKGROUND: This study serves to establish the re-endoscopy rate in patients
      undergoing surgery for colorectal cancer (CRC) at a tertiary academic center and
      to identify significant factors that may influence the decision for preoperative
      re-endoscopy. METHODS: A retrospective review of 341 consecutive patients
      undergoing elective surgical resection for CRC was performed from January 2008 to
      December 2011. Descriptive statistics were used to define the patient population
      and to establish the institutional re-endoscopy rate. In order to identify
      factors associated with re-endoscopy, univariate and multivariate analysis was
      performed using the chi square test and logistic regression modeling. RESULTS:
      Patients within the two comparison groups had similar demographic profiles.
      Excluding patients where the primary endoscopist was the operating surgeon, 121
      of 299 patients (40.5%) underwent re-endoscopy. The most common reasons for re
      endoscopy included tattooing of the lesion in 55 patients (45.5%), surgical
      planning in 43 (35.5%), and repeated therapeutic attempts in 11 (9%). Significant
      factors associated with re-endoscopy included left-sided colon cancers (compared
      to right-sided lesions, P < 0.001), planned laparoscopic procedures (P = 0.011),
      and the absence of a tattoo on the first colonoscopy (P = 0.010). There was also
      a trend toward a reduction in re-endoscopy if the operating surgeon was consulted
      at the time of the initial endoscopy (P = 0.085). There was a clear trend toward
      increased laparoscopic procedures over the duration of the study (P < 0.001).
      Although this did not correlate with an increase in re-endoscopy, it did coincide
      with a significant increase in preoperative tattooing at the first colonoscopy (P
      < 0.001). CONCLUSIONS: The repeat preoperative endoscopy rate in CRC patients was
      40.5%. Re-endoscopy was associated with an initial failure to tattoo the lesion,
      left-sided colonic neoplasms, and a planned laparoscopic resection. Further
      research is needed to help identify which patients would benefit from re
      endoscopy and where this may be safely omitted.

PMID- 24853843
TI  - Cardiovascular risk in obese diabetic patients is significantly reduced one year
      after gastric bypass compared to one year of diabetes support and education.
AB  - BACKGROUND: Roux-en-Y gastric bypass (RYGB) reduces most of the obesity-related
      comorbidities known to increase the cardiovascular risk in obese subjects. The
      Framingham risk score (FRS) is designed to be independent of body weight and
      estimates the 10-year risk for coronary heart disease (CHD), myocardial
      infarction, stroke, cardiovascular disease (CVD), death from CHD, and death from
      CVD. Our aim was to evaluate the effectiveness of RYGB on improving the FRS when
      compared to a matched control group who underwent diabetes support and education
      program (DSE). METHODS: In a prospective cohort study, we evaluated
      preoperatively and at 12 months, 61 morbidly obese subjects with diabetes. Thirty
      underwent laparoscopic RYGB, and 31 received 1 year of DSE, consisting of
      educational sessions on diet, nutrition, and exercise. Groups were matched for
      gender, age, weight, blood pressure, and cholesterol and triglyceride levels.
      Strict gender-specific FRS was used to assess the cardiovascular risk. RESULTS:
      Excess weight-loss percentages (%EWL) were 55.6 +/- 15.1 in the RYGB group and
      1.2 +/- 10.8 in the DSE group (P < 0.001). The two groups were matched for
      baseline FRS. RYGB patients experienced a significant decrease in all FRS,
      whereas control subjects did not show a significant decrease for the 10-year risk
      for CHD, CVD and death from CVD. The between-group differences for changes from
      baseline to 12 months in all FRS were significant. The 10-year risk reductions
      for CHD, MI, stroke, CVD, death from CHD, and death from CVD in the RYGB group
      relative to the DSE group were, respectively, 42, 48, 30, 39, 50, and 50%. No
      correlations between reduction in FRS and %EWL were found after RYGB.
      CONCLUSIONS: A significant improvement in the 10 year estimated cardiovascular
      risk is observed in patients undergoing RYGB, but not in those who were offered
      usual medical therapy plus DSE. However, the effects of RYGB on FRS are
      independent of weight loss.

PMID- 24853844
TI  - Frequent occurrence of fever in patients who have undergone endoscopic submucosal
      dissection for colorectal tumor, but bacteremia is not a significant cause.
AB  - BACKGROUND: We examined the incidence of and factors associated with fever, as
      well as the frequency of bacteremia, in patients who had undergone endoscopic
      submucosal dissection (ESD) for colorectal tumor. METHOD: A total of 199 patients
      (120 male and 79 female) were included. The patients were classified into two
      groups based on the body temperature on the day after ESD treatment: group A,
      body temperature <37  degrees C; and group B, body temperature >=37  degrees C.
      The following factors were analyzed to determine their potential association with
      post-ESD fever: gender, age, tumor size, form, location, and presence or absence
      of intraoperative perforation. In addition, blood samples from 50 patients were
      obtained for blood culture and 16S rRNA gene analysis by polymerase chain
      reaction. RESULTS: Group A included 106 patients (70 male and 36 female), with a
      median age of 63 years. Group B included 93 patients (50 male and 43 female),
      with a median age of 70 years. The incidence of post-ESD fever in the entire
      cohort was 46.7%. Univariate analysis based on comparison between groups A and B
      showed that the following factors were significantly associated with post-ESD
      fever: age [mean +/- standard deviation (SD)], 64.5 +/- 9.2 versus 68.5 +/- 10.8
      years, P = 0.006; and tumor size (mean +/- SD) 30.6 +/- 10.8 versus 39.1 +/- 16.6
      mm, P < 0.001. Logistic regression analysis for post-ESD fever also found that
      age {odds ratio 1.04 (95% CI [1.01-1.07], P = 0.009)} and lesion size {odds ratio
      1.05 (95% CI [1.03-1.08], P = 0.0002)} were closely associated with post-ESD
      fever. Of the 50 patients who had blood samples cultured and 16S rRNA gene
      analyzed, bacteria in blood culture and the 16S rRNA gene were not detectable in
      any of the samples from the 50 patients. CONCLUSIONS: This study indicated that
      older patients and patients with large tumors were more likely to develop post
      ESD fever, but there was a low probability that bacteremia was the cause of
      fever.

PMID- 24853845
TI  - Laparoendoscopic single-site adrenalectomy versus conventional laparoscopic
      adrenalectomy: a comparison of surgical outcomes and an analysis of a single
      surgeon's learning curve.
AB  - BACKGROUND: Conventional laparoscopic adrenalectomy (LA) is the gold standard
      procedure for benign adrenal tumors. Laparoendoscopic single-site adrenalectomy
      (LESS-A) has been developed as an extension of standard laparoscopic minimally
      invasive procedures. METHODS: This retrospective study compared the first
      experience of one surgeon with 70 LESS-A to 140 LA cases with respect to
      evaluating the influence of the inexperience on surgical outcomes and to assess
      this surgeon's learning curve for LESS-A. RESULTS: Age, gender, BMI, percentage
      of patients with prior abdominal surgery, tumor laterality, and tumor size were
      all comparable between the two groups. There were no statistically significant
      differences in any surgical outcomes, including mean operative time,
      pneumoperitoneum time, estimated blood loss, transfusion requirements, hemoglobin
      decrease at postoperative day 1, analgesic requirements, postoperative day of
      oral intake, conversion rate, or morbidity between the two groups. The one
      exception was hospital stay. There were no mortalities or reoperations in either
      group. The morbidity rates in the LESS-A group and LA group were 4.2 and 6.4%,
      respectively (p = 0.528). LESS-A appears to have a steep learning curve and the
      operative time of the initial 70 cases decreased markedly and remained stable
      when the experience level exceeded 12 cases. There was no morbidity or conversion
      in these first 12 LESS-A cases. Multiple regression analysis revealed that
      surgeon experience (p = 0.008) and tumor size (p = 0.001) were independent
      predictors of prolonged operative time. CONCLUSIONS: Surgical outcomes of LESS-A
      were equivalent to those of LA without compromising safety. The introduction of
      LESS-A at our hospital was smooth and safe. While the indication for LESS-A has
      been controversial, LESS-A was a useful procedure, especially for cases in which
      cosmesis is of paramount importance.

PMID- 24853846
TI  - Successful total shift from multiport to single-port laparoscopic surgery in low
      anterior resection of colorectal cancer.
AB  - OBJECTIVE: To assess the possibility of using single-port low anterior resection
      (LAR) in place of conventional laparoscopic LAR. BACKGROUND: Though single-port
      LS is gradually evolving, the application of single-port LS techniques in LAR
      have been viewed with skepticism due to technical difficulties. METHODS: Data
      from patients who had undergone either conventional laparoscopic LAR (n = 49) or
      single-port LAR (n = 67) for colorectal cancers between March 2006 and March 2013
      were analyzed retrospectively. RESULTS: In single-port LAR group, oncologic
      outcomes were satisfactory with respect to attainment of lymph nodes (23.4 +/-
      15.3) and surgical margins (proximal cut margin: 7.1 +/- 4.6 cm, distal cut
      margin: 7.7 +/- 5.7 cm). Single-port LAR showed acceptable clinical outcomes
      manifested by comparable outcomes of post-operative analgesics requirement and
      length of hospital stay, and by low incidence of post-operative complications
      (conventional laparoscopic LAR group: 30.6% vs. single-port LAR group: 14.9%; P <
      0.01). Operative time was comparable between groups (conventional laparoscopic
      LAR group: 309 +/- 93 min vs. single-port LAR group: 277 +/- 106 min; P = 0.097).
      Throughout a series of 67 consecutive single-port LARs, no conversion to
      multiport or open surgery was occurred. CONCLUSION: This study shows that single
      port LAR is both safe and feasible for use in resection of colorectal cancer when
      performed by surgeons who are trained in conventional laparoscopic technique. If
      further and more extensive studies support our results, then single-port LAR can
      be an acceptable alternative to conventional laparoscopic LAR for treatment of
      colorectal cancer.

PMID- 24853847
TI  - A tailored approach for endoscopic treatment of small rectal neuroendocrine
      tumor.
AB  - INTRODUCTION: Resection of rectal neuroendocrine tumors (NETs) less than 1 cm in
      diameter can be performed using various endoscopic techniques. Endoscopic mucosal
      resection (EMR) traditionally had suboptimal complete resection rate compared to
      endoscopic submucosal resection with band ligation (ESMR-L). However, the
      previous studies did not consider the characteristics of rectal NETs. The aim of
      our study is to compare the efficacy of ESMR-L and EMR using tailored approach
      according to the characteristics of rectal NETs. METHODS: 82 rectal NETs in 77
      patients treated by ESMR-L (n = 48) or EMR (n = 34) between September 2007 and
      October 2012 were retrospectively analyzed. ESMR-L was used for flat-type tumors
      or tumors with non-lifting sign after submucosal injection. Conventional EMR was
      used for elevated-type tumors or tumors with well-lifting sign after submucosal
      injection. RESULTS: The pathological complete resection rate was higher in the
      ESMR-L group (45 lesions, 93.8%) compared with the EMR group (30 lesions, 88.2%);
      however, this difference was not significant (p = 0.441). Overall complication
      did not differ significantly between the ESMR-L group and the EMR group (p =
      0.774). There was one case of a remnant lesion in the ESMR-L group, which was
      managed by EMR after circumferential pre-cutting (EMR-P), and no recurrence has
      been detected in either the ESMR-L or EMR group. CONCLUSIONS: ESMR-L and EMR
      procedures could have a similar excellent complete resection rate, if we select
      the endoscopic resection technique according to the characteristics of the small
      rectal NETs.

PMID- 24853849
TI  - Factors affecting the technical difficulty and clinical outcome of endoscopic
      submucosal dissection for colorectal tumors.
AB  - BACKGROUND: Endoscopic submucosal dissection (ESD) for colorectal tumors is
      technically difficult due to the anatomy of the large intestine, with its narrow
      lumen, thin walls, and redundancy. Here, we assessed factors associated with
      incomplete resection and difficult colorectal ESD. METHODS: Between November 2009
      and April 2013, we performed ESD on 151 consecutive colorectal tumors in 147
      patients. We evaluated the clinical outcomes of all cases and conducted multiple
      logistic regression analysis of the following factors related to incomplete
      resection and difficult procedure: age, gender, location (right colon, left colon
      or rectum), tumor size (diameter >=40 or <40 mm), operation time, morphology
      [granular-type laterally spreading tumor (LST-G), non-granular-type laterally
      spreading tumor (LST-NG), or protruded type], fibrosis, and paradoxical movement
      during the procedure. A procedure that required more than 120 min was defined as
      a difficult colorectal ESD. RESULTS: Average tumor size was 32.1 +/- 10.7 mm, and
      the average procedure length was 71.8 +/- 49.5 min. The rate of en bloc resection
      was 94.7%, while that of en bloc curative resection was 86.8%. Perforation
      occurred in 1.3% of the ESD procedures. Multivariate logistic regression analysis
      revealed that only severe fibrosis [odds ratio (OR) 4.51; 95% confidence interval
      (CI) 1.36-14.91, p = 0.014] contributed to incomplete resection and that a tumor
      size exceeding 40 mm (OR 5.73 [95% CI 1.66-19.74], p = 0.006), severe fibrosis
      (OR 23.31 [95% CI 6.59-82.54], p < 0.001), and paradoxical movement (OR 4.26 [95%
      CI 1.11-16.44], p = 0.035) were independent factors exacerbating the difficulty
      of colorectal ESD. CONCLUSIONS: Severe fibrosis contributed to both incomplete
      resection and difficult colorectal ESD. Larger tumor size and paradoxical
      movement during the procedure were independent factors contributing to the
      difficulty of colorectal ESD. These factors might enable endoscopists to develop
      strategies for treating colorectal ESD.

PMID- 24853848
TI  - Monitoring c-reactive protein after laparoscopic colorectal surgery excludes
      infectious complications and allows for safe and early discharge.
AB  - BACKGROUND: Early detection of infectious complications is urgently needed in the
      era of DRG-based compensation. This work assessed the diagnostic accuracy of c
      reactive protein (CRP) level in the detection of infectious complications after
      laparoscopic colorectal resection. METHODS: Laparoscopic colorectal resections
      were identified from a prospective database. Complications were graded according
      to the Dindo-Clavien classification. Surgical site infections were defined
      according to the Centers of Disease Control. CRP level was routinely measured
      until postoperative day (POD) 7. Uni- and multivariate analysis were performed.
      Diagnostic accuracy was evaluated using receiver operating curves. RESULTS: 355
      patients were operated for diverticulosis (88.7%), neoplasia (6.8%), and other
      causes (4.5%). Mean age and body mass index were 59.8 +/- 13.7 years and 26.5 +/-
      15 kg/m(2). Left, right, and total laparoscopic colectomies were performed in
      316, 33, and 6 patients. Complications occurred in 85 patients and 16 patients
      (4.5%) were reoperated. Fifty-one patients (14.4%) suffered from infectious
      complications at a median of 6 POD, while 9 anastomoses leaked (2.7%). In
      multivariate analysis, presence of an abscess at surgery was predictive of an
      infectious complication (OR 2.5, 95% CI 1.1-5.3), as were a body mass index >30
      kg/m(2) and operative time >160 min in a bootstrap analysis. Overall, CRP peaked
      on POD 2 and declined thereafter. Most infectious complications were apparent
      starting on POD 6. A CRP <56 mg/l on POD 4 had a negative predictive value of
      100% (95% CI 94.9-100%) to rule out infectious complications. Above 56 mg/l,
      sensitivity was 100% (95% CI 0.8-1) and specificity 49% (95% CI 0.4-0.6) for the
      development of infectious complications in the absence of clinical signs. This
      translated into a remarkable diagnostic accuracy of 78% (95% CI 0.7-0.9).
      CONCLUSION: Monitoring CRP level in laparoscopic colorectal surgery demonstrated
      a high diagnostic accuracy for infectious complications, thus allowing for safe
      and early discharge.

PMID- 24853850
TI  - Outcome and complications of endoscopic balloon dilatations in various types of
      ileocaecal and colonic stenosis in patients with Crohn's disease.
AB  - AIM: We examined the outcome and the complications of endoscopic balloon
      dilatation (EBD) of ileocaecal and colonic strictures due to Crohn's disease.
      METHODS: We examined 237 dilatation procedures in 77 patients with symptomatic
      ileocaecal and colonic stenosis regarding outcome, individual perforation risk,
      the need for further interventions, and other complications within a 10 years
      observation period. RESULTS: In 50 of 77 patients (64.9%), endoscopic dilatation
      procedures were successful within a median follow-up period of 24 months (25th
      and 75th percentile 10-38.5 months). Thirty five patients (45.5%) were
      successfully dilated with only one endoscopic procedure, while the remaining
      patients required two or more EBDs. Albeit the EBD, 27 patients of the whole
      cohort (35.1%) underwent surgical repair of the stenosis in due course. Overall
      complication rate was 7.6%, with postdilatation bleeding in 1.7% and abdominal
      pain longer than 24 h in 4.2%. Perforation occurred in 4 of 77 patients (5.2%),
      resulting in a perforation rate of 1.7% per intervention, or, more importantly,
      for the individual patient in a long-term perforation rate of 5.2% per patient,
      respectively. DISCUSSION: Endoscopic balloon dilatation (EBD) is a safe and
      effective approach to ileocaecal and colonic stenosis in approximately 65% of
      Crohn's disease patients. Even in case of recurrence, further endoscopic
      treatments can be undertaken. The perforation rate depending on the number of
      interventions is low, but for the individual patient a cumulative per patient
      perforation risk of 5.2% in the long-term should be considered during patient
      information and decisions for or against surgical interventions.

PMID- 24853851
TI  - Perioperative outcomes of laparoscopic and robot-assisted major hepatectomies: an
      Italian multi-institutional comparative study.
AB  - BACKGROUND: Laparoscopic major hepatectomy (LMH), although safely feasible in
      experienced hands and in selected patients, is a formidable challenge because of
      the technical demands of controlling hemorrhage, sealing bile ducts, avoiding gas
      embolism, and maintaining oncologic surgical principles. The enhanced surgical
      dexterity offered by robotic assistance could improve feasibility and/or safety
      of minimally invasive major hepatectomy. The aim of this study was to compare
      perioperative outcomes of LMH and robotic-assisted major hepatectomy (RMH).
      METHODS: Pooled data from four Italian hepatobiliary centers were analyzed
      retrospectively. Demographic data, operative, and postoperative outcomes were
      collected from prospectively maintained databases and compared. RESULTS: Between
      January 2009 and December 2012, 25 patients underwent LMH and 25 RMH. The two
      groups were comparable for all baseline characteristics including type of
      resection and underlying pathology. Conversion to open surgery was required in
      one patient in each group (4%). No difference was noted in operative time,
      estimated blood, and need for allogenic blood transfusions. Intermittent pedicle
      occlusion was required only in LMH (32% vs. 0; p = 0.004). Length of hospital
      stay, including time spent in intensive care unit, was similar between the two
      groups, but patients undergoing LMH showed quicker recovery of bowel activity,
      with shorter time to first flatus (1 vs. 3 days; p = 0.023) and earlier tolerance
      to oral liquid diet (1 vs. 2 days; p = 0.001). No difference was noted in
      complication rate, 90-day mortality, and readmission rate. CONCLUSIONS: This
      retrospective multi-institution study confirms that selected patients can safely
      undergo minimally invasive major hepatectomy, either LMH or RMH. The fact that
      intermittent pedicle occlusion could be avoided in RMH suggests improved surgical
      ability to deal with bleeding during liver transection, but further studies are
      needed before any final conclusion can be drawn.

PMID- 24853852
TI  - Feasibility of transumbilical anatomic pulmonary lobectomy in a canine model.
AB  - PURPOSE: Transthoracic thoracoscopic lobectomy is the preferred method of
      surgical treatment for early lung cancer. Current methods require a transthoracic
      approach and are associated with chronic postoperative pain in up to 25% of
      patients. Single-port transumbilical uniport surgery may offer advantages over
      multiport surgery with less postoperative pain and better cosmetic results. The
      aim of this study was to evaluate the feasibility of a transumbilical anatomic
      lobectomy of the lung (TUAL) in a canine model. METHODS: TUAL was performed in 12
      beagle dogs using a 3-cm umbilical incision combined with a 2.5-cm diaphragmatic
      incision. Variables evaluated for surgical outcomes were operating time,
      operative complications, body rectal temperature, respiratory rate, white blood
      cell count, and arterial blood gases. RESULTS: TUAL was successfully completed in
      ten animals. There were six bleeding complications related to surgery. In four
      animals, an avulsion of pulmonary vessel causes intraoperative bleeding,
      requiring simultaneous pulmonary artery and bronchus resections. In one animal,
      slipping of endoclip after vessel clipping caused perioperative bleeding. The
      other animal encountered bleeding complication during dissection of inferior
      pulmonary vein. Both animals required conventional thoracotomy to complete the
      surgery. CONCLUSIONS: TUAL in the canine model is feasible but associated with
      significant morbidity. With further development and refinement of instruments,
      comparative studies between the novel transumbilical lobectomy and the current
      video-assisted transthoracic lobectomy will clarify the role of transumbilical
      lobectomy in thoracic surgery.

PMID- 24853853
TI  - Pure transumbilical SILS gastric bypass with mechanical circular gastrojejunal
      anastomosis feasibility.
AB  - BACKGROUND: Since Wittgrove introduced the laparoscopic version of the gastric
      bypass in 1994, the interest still remains in the decrease of the abdominal wall
      trauma in order to optimize the benefits of laparoscopy on postoperative pain,
      cosmesis, hospital stay, and convalescence in bariatric patients. This work is to
      report the feasibility of gastric bypass surgery by a pure transumbilical single
      incision laparoscopic surgery (SILS) with a mechanical circular gastrojejunal
      anastomosis. METHODS: Thirty-four patients (10 males and 24 females) were offered
      to receive gastric bypass with circular mechanical gastrojejunal anastomosis by
      Single Incision Laparoscopic Surgery (SILS) using pure transumbilical access.
      Anastomotic leak occurrence was the primary end-point. Patients demographics,
      operative time, additional trocarts, hemorrhage, intra abdominal abscess, length
      of post-operative stay, readmission, 30 days death, gastrojejunal anastomosis
      stricture, marginal ulcers, reflux complains, seromas, incisional hernias, and %
      excess BMI loss were also recorded in a prospective database. RESULTS: Primary
      end-point showed no anastomotic leak occurrence during the hospital stay or
      during the first 30 post-operative days. SILS gastric bypass with a circular
      mechanical gastrojejunal anastomosis is feasible and seems to be safe.

PMID- 24853854
TI  - An extended proximal esophageal myotomy is necessary to normalize EGJ
      distensibility during Heller myotomy for achalasia, but not POEM.
AB  - BACKGROUND: For laparoscopic Heller myotomy (LHM), the optimal myotomy length
      proximal to the esophagogastric junction (EGJ) is unknown. In this study, we used
      a functional lumen imaging probe (FLIP) to measure EGJ distensibility changes
      resulting from variable proximal myotomy lengths during LHM and peroral
      esophageal myotomy (POEM). METHODS: Distensibility index (DI) (defined as the
      minimum cross-sectional area at the EGJ divided by pressure) was measured with
      FLIP after each operative step. During LHM and POEM, each patient's myotomy was
      performed in two stages: first, a myotomy ablating only the EGJ complex was
      created (EGJ-M), extending from 2 cm proximal to the EGJ, to 3 cm distal to it.
      Next, the myotomy was lengthened 4 cm further cephalad to create an extended
      proximal myotomy (EP-M). RESULTS: Measurements were performed in 12 patients
      undergoing LHM and 19 undergoing POEM. LHM resulted in an overall increase in DI
      (1.6 +/- 1 vs. 6.3 +/- 3.4 mm(2)/mmHg, p < 0.001). Creation of an EGJ-M resulted
      in a small increase (1.6-2.3 mm(2)/mmHg, p < 0.01) and extension to an EP-M
      resulted in a larger increase (2.3-4.9 mm(2)/mmHg, p < 0.001). This effect was
      consistent, with 11 (92%) patients experiencing a larger increase after EP-M than
      after EGJ-M. Fundoplication resulted in a decrease in DI and deinsufflation an
      increase. POEM resulted in an increase in DI (1.3 +/- 1 vs. 9.2 +/- 3.9
      mm(2)/mmHg, p < 0.001). Both creation of the submucosal tunnel and performing an
      EGJ-M increased DI, whereas lengthening of the myotomy to an EP-M had no
      additional effect. POEM resulted in a larger overall increase from baseline than
      LHM (7.9 +/- 3.5 vs. 4.7 +/- 3.3 mm(2)/mmHg, p < 0.05). CONCLUSIONS: During LHM,
      an EP-M was necessary to normalize distensibility, whereas during POEM, a myotomy
      confined to the EGJ complex was sufficient. In this cohort, POEM resulted in a
      larger overall increase in EGJ distensibility.

PMID- 24853855
TI  - Risk factors for anastomotic leakage after laparoscopic low anterior resection
      with DST anastomosis.
AB  - BACKGROUND: Laparoscopic rectal surgery involving rectal transection and
      anastomosis with stapling devices is technically difficult. The aim of this study
      was to evaluate the risk factors for anastomotic leakage (AL) after laparoscopic
      low anterior resection (LAR) with double-stapling technique (DST) anastomosis.
      METHODS: This was a retrospective single-institution study of 154 rectal cancer
      patients who underwent laparoscopic LAR with DST anastomosis between June 2005
      and August 2013. Patient-, tumor-, and surgery-related variables were examined by
      univariate and multivariate analyses. The outcome of interest was clinical AL.
      RESULTS: The overall AL rate was 12.3% (19/154). In univariate analysis, tumor
      size (P = 0.001), operative time (P = 0.049), intraoperative bleeding (P =
      0.037), lateral lymph node dissection (P = 0.009), multiple firings of the linear
      stapler (P = 0.041), and precompression before stapler firings (P = 0.008) were
      significantly associated with AL. Multivariate analysis identified tumor size
      (odds ratio [OR] 4.01; 95% confidence interval [CI] 1.25-12.89; P = 0.02) and
      precompression before stapler firings (OR 4.58; CI 1.22-17.20; P = 0.024) as
      independent risk factors for AL. In particular, precompression before stapler
      firing tended to reduce the AL occurring in early postoperative period.
      CONCLUSIONS: Using appropriate techniques, laparoscopic LAR with DST anastomosis
      can be performed safely without increasing the risk of AL. Important risk factors
      for AL were tumor size and precompression before stapler firings.

PMID- 24853856
TI  - Successful treatment of refractory Guillain-Barre syndrome with alemtuzumab in a
      patient with chronic lymphocytic leukemia.
AB  - This is the case of a 79-year-old man with chronic lymphocytic leukemia who
      presented with Guillain-Barre syndrome with features overlapping with the Miller
      Fisher syndrome and Bickerstaff brainstem encephalitis and positive
      antiganglioside GQ1b antibody about 6 months after treatment with bendamustine
      and rituximab. His clinical and neurologic condition continued to deteriorate
      despite sequential treatment with corticosteroids, intravenous immunoglobulin and
      plasmapheresis, but in the end, he had a complete and durable response to
      treatment with alemtuzumab.

PMID- 24853858
TI  - Chromatin organisation in duckweed interphase nuclei in relation to the nuclear
      DNA content.
AB  - The accessibility of DNA during fundamental processes, such as transcription,
      replication and DNA repair, is tightly modulated through a dynamic chromatin
      structure. Differences in large-scale chromatin structure at the microscopic
      level can be observed as euchromatic and heterochromatic domains in interphase
      nuclei. Here, key epigenetic marks, including histone H3 methylation and 5
      methylcytosine (5-mC) as a DNA modification, were studied cytologically to
      describe the chromatin organisation of representative species of the five
      duckweed genera in the context of their nuclear DNA content, which ranged from
      158 to 1881 Mbp. All studied duckweeds, including Spirodela polyrhiza with a
      genome size and repeat proportion similar to that of Arabidopsis thaliana, showed
      dispersed distribution of heterochromatin signatures (5mC, H3K9me2 and H3K27me1).
      This immunolabelling pattern resembles that of early developmental stages of
      Arabidopsis nuclei, with less pronounced heterochromatin chromocenters and
      heterochromatic marks weakly dispersed throughout the nucleus.

PMID- 24853857
TI  - Synaptically released matrix metalloproteinase activity in control of structural
      plasticity and the cell surface distribution of GluA1-AMPA receptors.
AB  - Synapses are particularly prone to dynamic alterations and thus play a major role
      in neuronal plasticity. Dynamic excitatory synapses are located at the membranous
      neuronal protrusions called dendritic spines. The ability to change synaptic
      connections involves both alterations at the morphological level and changes in
      postsynaptic receptor composition. We report that endogenous matrix
      metalloproteinase (MMP) activity promotes the structural and functional
      plasticity of local synapses by its effect on glutamate receptor mobility and
      content. We used live imaging of cultured hippocampal neurons and quantitative
      morphological analysis to show that chemical long-term potentiation (cLTP)
      induces the permanent enlargement of a subset of small dendritic spines in an MMP
      dependent manner. We also used a superresolution microscopy approach and found
      that spine expansion induced by cLTP was accompanied by MMP-dependent
      immobilization and synaptic accumulation as well as the clustering of GluA1
      containing AMPA receptors. Altogether, our results reveal novel molecular and
      cellular mechanisms of synaptic plasticity. 

PMID- 24853859
TI  - Towards standardisation of cell-free DNA measurement in plasma: controls for
      extraction efficiency, fragment size bias and quantification.
AB  - Circulating cell-free DNA (cfDNA) is becoming an important clinical analyte for
      prenatal testing, cancer diagnosis and cancer monitoring. The extraction stage is
      critical in ensuring clinical sensitivity of analytical methods measuring
      minority nucleic acid fractions, such as foetal-derived sequences in
      predominantly maternal cfDNA. Consequently, quality controls are required for
      measurement of extraction efficiency, fragment size bias and yield for validation
      of cfDNA methods. We evaluated the utility of an external DNA spike for
      monitoring these parameters in a study comparing three specific cfDNA extraction
      methods [QIAamp circulating nucleic acid (CNA) kit, NucleoSpin Plasma XS (NS) kit
      and FitAmp plasma/serum DNA isolation (FA) kit] with the commonly used QIAamp DNA
      blood mini (DBM) kit. We found that the extraction efficiencies of the kits
      ranked in the order CNA kit > DBM kit > NS kit > FA kit, and the CNA and NS kits
      gave a better representation of smaller DNA fragments in the extract than the DBM
      kit. We investigated means of improved reporting of cfDNA yield by comparing
      quantitative PCR measurements of seven different reference gene assays in plasma
      samples and validating these with digital PCR. We noted that the cfDNA quantities
      based on measurement of some target genes (e.g. TERT) were, on average, more than
      twofold higher than those of other assays (e.g. ERV3). We conclude that analysis
      and averaging of multiple reference genes using a GeNorm approach gives a more
      reliable estimate of total cfDNA quantity.

PMID- 24853860
TI  - Complement functional tests for monitoring eculizumab treatment in patients with
      atypical hemolytic uremic syndrome.
AB  - BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is a thrombotic
      microangiopathy characterized by hemolysis, platelet consumption, and renal
      injury. Eculizumab, a mAb that blocks complement activity, has been successfully
      used in aHUS. OBJECTIVES: To optimize eculizumab therapy in aHUS patients by
      monitoring complement functional tests and markers of disease activity.
      PATIENTS/METHODS: We studied 18 patients with aHUS (10 males; eight females; age
      range, 2-40 years) treated with eculizumab to induce and/or maintain disease
      remission. Patients were followed up for a cumulative observation period of 160
      months, during which blood samples were obtained at various time intervals to
      measure complement activity (Wieslab for the classical, alternative and mannose
      binding lectin complement pathways) and the parameters of disease activity
      (haptoglobin and lactate dehydrogenase serum levels, and platelet count). The
      intravenous eculizumab doses of 12-33 mg kg(-1) were initially administered every
      week, with the interval between doses being gradually extended to 2 weeks, 3
      weeks and 4 weeks on the basis of strict laboratory and clinical control.
      RESULTS: Complement activity was normal before eculizumab treatment, regardless
      of the state of the disease (activity or remission). It was completely suppressed
      1 week, 2 weeks and 3 weeks after the last eculizumab infusion (mean values +/-
      standard deviation: 1% +/- 1% to 3% +/- 5% for both the classical and alternative
      pathways; P = 0.0001 vs. baseline), and partially suppressed after 4 weeks (22%
      +/- 26% and 16% +/- 27%; P = 0.0001 vs. baseline). The increase in the time
      interval between eculizumab infusions did not change disease activity markers.
      CONCLUSIONS: Monitoring complement tests can allow a safe reduction in the
      frequency of eculizumab administration in aHUS while keeping the disease in
      remission.

PMID- 24853861
TI  - Vascular endothelial cadherin and vascular endothelial growth factor in
      periodontitis and smoking.
AB  - OBJECTIVE: This study investigated the vascularization in periodontal disease
      process via revealing: (i) vascular endothelial cadherin (VE-cadherin) and
      vascular endothelial growth factor (VEGF) productions in periodontitis and (ii)
      the impact of smoking on this phenomenon. MATERIALS AND METHODS: Fifteen smokers
      and 15 non-smokers with/without periodontitis were allocated by split-mouth
      randomization regarding their smoking and periodontal statuses. The teeth with
      periodontitis in smokers (group 1), without periodontitis in smokers (group 2),
      with periodontitis in non-smokers (group 3), and without periodontitis in non
      smokers (group 4) constituted the study groups. Gingival crevicular fluid (GCF)
      levels of VE-cadherin and VEGF were determined by ELISA to evaluate their
      profiles in the groups. RESULTS: There were increased VE-cadherin levels in
      groups 1 and 3 compared with groups 2 and 4 (P < 0.05). Group 2 demonstrated
      higher VE-cadherin level than group 4 (P < 0.05). Increased VEGF was noted in
      groups 1 and 3 compared with groups 2 and 4 (P < 0.05) with similar levels
      between groups 1 and 3 and groups 2 and 4 (P > 0.05). There were no correlations
      between the VE-cadherin and VEGF levels in all groups (P > 0.05). CONCLUSION: The
      results suggest that VE-cadherin and VEGF may increase in periodontitis, and
      smoking may uniquely cause VE-cadherin production in GCF.

PMID- 24853863
TI  - Adherence in patients in the first year after kidney transplantation and its
      impact on graft loss and mortality: a cross-sectional and prospective study.
AB  - AIMS: To explore the predictive value of adherence to their immunosuppressive
      medication in kidney transplant recipients in the first year after kidney
      transplantation as a determinant of graft loss and mortality up to 12 years
      (prospective analysis) and its association with sociodemographic and medical
      factors and social support (cross-sectional analysis). BACKGROUND: Poor adherence
      to their immunosuppressive medication in kidney transplant recipients remains the
      leading preventable cause of poor patient outcomes. DESIGN: Prospective and cross
      sectional study. METHODS: At baseline, 325 patients 3-12 months
      posttransplantation were invited to participate. Adherence was assessed using
      collateral reports - a combination of patients' self-evaluation and an estimate
      by their nephrologist. The patients provided sociodemographic and medical data
      and completed the End-Stage Renal Disease Symptom Checklist and Multidimensional
      scale of perceived social support. At follow-up (average 7.1 years), data on
      patients and graft survival were obtained. All data were collected from 2002
      2013. Multinomial regression analysis and Cox regression were performed. RESULTS:
      A total of 297 patients (48.1 (12.8) years, 61.6% men) agreed to participate
      (response rate 91.4%); 67.4% were considered as fully adherent. Poor adherence
      was associated with higher risk of graft loss and mortality over 12 years. Female
      sex, higher education, higher perceived side effects of corticosteroids, better
      perceived cardiac and renal function and higher perceived family social support
      in the first year posttransplantation were associated with full adherence to
      immunosuppressive treatment. CONCLUSIONS: Patients with poor adherence to the
      immunosuppressive medication in the first year after kidney transplantation
      showed increased likelihood of graft loss and death over 12 years compared with
      the adherent patients.

PMID- 24853864
TI  - A random matrix approach to credit risk.
AB  - We estimate generic statistical properties of a structural credit risk model by
      considering an ensemble of correlation matrices. This ensemble is set up by
      Random Matrix Theory. We demonstrate analytically that the presence of
      correlations severely limits the effect of diversification in a credit portfolio
      if the correlations are not identically zero. The existence of correlations
      alters the tails of the loss distribution considerably, even if their average is
      zero. Under the assumption of randomly fluctuating correlations, a lower bound
      for the estimation of the loss distribution is provided. 

PMID- 24853862
TI  - A reciprocal model of face recognition and autistic traits: evidence from an
      individual differences perspective.
AB  - Although not a core symptom of the disorder, individuals with autism often
      exhibit selective impairments in their face processing abilities. Importantly,
      the reciprocal connection between autistic traits and face perception has rarely
      been examined within the typically developing population. In this study,
      university participants from the social sciences, physical sciences, and
      humanities completed a battery of measures that assessed face, object and emotion
      recognition abilities, general perceptual-cognitive style, and sub-clinical
      autistic traits (the Autism Quotient (AQ)). We employed separate hierarchical
      multiple regression analyses to evaluate which factors could predict face
      recognition scores and AQ scores. Gender, object recognition performance, and AQ
      scores predicted face recognition behaviour. Specifically, males, individuals
      with more autistic traits, and those with lower object recognition scores
      performed more poorly on the face recognition test. Conversely, university major,
      gender and face recognition performance reliably predicted AQ scores. Science
      majors, males, and individuals with poor face recognition skills showed more
      autistic-like traits. These results suggest that the broader autism phenotype is
      associated with lower face recognition abilities, even among typically developing
      individuals. 

PMID- 24853866
TI  - Ambulatory cancer and US general population reference values and cutoff scores
      for the functional assessment of cancer therapy.
AB  - BACKGROUND: Health-related quality of life (HRQOL) measures are commonly used in
      oncology research. Interest in their use for monitoring or screening is
      increasing. The Functional Assessment of Cancer Therapy (FACT) is one of the most
      widely used HRQOL instruments. Consequently, oncology researchers and
      practitioners have an increasing need for reference values for the Functional
      Assessment of Cancer Therapy-General (FACT-G) and its 7-item rapid version, the
      Functional Assessment of Cancer Therapy-General 7 (FACT-G7), to compare FACT
      scores across specific subgroups of patients in research trials and practice. The
      objectives of this study are to provide 1) reference values from a sample of the
      general US adult population and a sample of adults diagnosed with cancer and 2)
      cutoff scores for quality of life. METHODS: A sample of the general US population
      (N = 1075) and a sample of patients with cancer from 12 studies (N = 5065) were
      analyzed. Cutoff scores were established using distribution- and anchor-based
      methods. Mean values for the cancer sample were analyzed by performance status,
      cancer type, and disease status. Also, t tests and established criteria for
      meaningful differences were used to compare values. RESULTS: FACT-G and FACT-G7
      scores in the general US population sample and cancer sample were generally
      comparable. Among the sample of patients with cancer, FACT-G and FACT-G7 scores
      worsened with declining performance status and increasing disease status.
      CONCLUSIONS: These data will aid interpretation of the magnitude and meaning of
      FACT scores, and allow for comparisons of scores across studies.

PMID- 24853865
TI  - Comparative analysis of carbohydrate binding properties of Sambucus nigra lectins
      and ribosome-inactivating proteins.
AB  - In the past three decades a lot of research has been done on the extended family
      of carbohydrate-binding proteins from Sambucus nigra, including several so-called
      type 2 RIPs as well as hololectins. Although all these proteins have been studied
      for their carbohydrate-binding properties using hapten inhibition assays,
      detailed carbohydrate specificity studies have only been performed for a few
      Sambucus proteins. In particular SNA-I, has been studied extensively. Because of
      its unique binding characteristics this lectin was developed as an important tool
      in glycoconjugate research to detect sialic acid containing glycoconjugates. At
      present much less information is available with respect to the detailed
      carbohydrate binding specificity of other S. nigra lectins and RIPs, and as a
      consequence their applications remain limited. In this paper we report a
      comparative analysis of several lectins from S. nigra using the glycan microarray
      technology. Ultimately a better understanding of the ligands for each lectin can
      contribute to new/more applications for these lectins in glycoconjugate research.
      Furthermore, the data from glycan microarray analyses combined with the
      previously obtained sequence information can help to explain how evolution within
      a single lectin family eventually yielded a set of carbohydrate-binding proteins
      with a very broad specificity range. 

PMID- 24853871
TI  - Miltefosine and antimonial drug susceptibility of Leishmania Viannia species and
      populations in regions of high transmission in Colombia.
AB  - BACKGROUND: Pentavalent antimonials have been the first line treatment for dermal
      leishmaniasis in Colombia for over 30 years. Miltefosine is administered as
      second line treatment since 2005. The susceptibility of circulating populations
      of Leishmania to these drugs is unknown despite clinical evidence supporting the
      emergence of resistance. METHODOLOGY/PRINCIPAL FINDINGS: In vitro susceptibility
      was determined for intracellular amastigotes of 245 clinical strains of the most
      prevalent Leishmania Viannia species in Colombia to miltefosine (HePC) and/or
      meglumine antimoniate (Sb(V)); 163, (80%) were evaluated for both drugs.
      Additionally, susceptibility to Sb(V) was examined in two cohorts of 85 L. V.
      panamensis strains isolated between 1980-1989 and 2000-2009 in the municipality
      of Tumaco. Susceptibility to each drug differed among strains of the same species
      and between species. Whereas 68% of L. V. braziliensis strains presented in vitro
      resistance to HePC, 69% were sensitive to Sb(V). Resistance to HePC and Sb(V)
      occurred respectively, in 20% y 21% of L. panamensis strains. Only 3% of L. V.
      guyanensis were resistant to HePC, and none to Sb(V). Drug susceptibility
      differed between geographic regions and time periods. Subpopulations having
      disparate susceptibility to Sb(V) were discerned among L. V. panamensis strains
      isolated during 1980-1990 in Tumaco where resistant strains belonged to zymodeme
      2.3, and sensitive strains to zymodeme 2.2. CONCLUSIONS/SIGNIFICANCE: Large scale
      evaluation of clinical strains of Leishmania Viannia species demonstrated
      species, population, geographic, and epidemiologic differences in susceptibility
      to meglumine antimoniate and miltefosine, and provided baseline information for
      monitoring susceptibility to these drugs. Sensitive and resistant clinical
      strains within each species, and zymodeme as a proxy marker of antimony
      susceptibility for L. V. panamensis, will be useful in deciphering factors
      involved in susceptibility and the distribution of sensitive and resistant
      populations.

PMID- 24853872
TI  - The interaction of affective states and cognitive vulnerabilities in the
      prediction of non-suicidal self-injury.
AB  - Non-suicidal self-injury (NSSI) is a serious public health concern and remains
      poorly understood. This study sought to identify both cognitive and affective
      vulnerabilities to NSSI and examine their interaction in the prediction of NSSI.
      A series of regressions indicated that low levels of positive affect (PA)
      moderated the relationships between self-criticism and brooding and NSSI. The
      associations of self-criticism and brooding with greater frequency of NSSI were
      attenuated by higher levels of PA. The interaction of cognitive and affective
      vulnerabilities is discussed within the context of current NSSI theory. 

PMID- 24853874
TI  - Case series describing an outbreak of highly resistant vancomycin Staphylococcus
      aureus (possible VISA/VRSA) infections in orthopedic related procedures in
      Guatemala.
AB  - This is a case series describing an outbreak of VRSA/VISA associated infections
      in orthopedic related procedures that occurred on a medical mission trip in
      Antigua, Guatemala. The paper describes the clinical features, microbiology and
      treatment options available to treat such infections in a Third World country. It
      also highlights the difficulty in making an accurate diagnosis with suboptimal
      microbiological support. 

PMID- 24853873
TI  - First evaluation of glucose-6-phosphate dehydrogenase (G6PD) deficiency in vivax
      malaria endemic regions in the Republic of Korea.
AB  - BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most
      common human enzyme defect and affects more than 400 million people worldwide.
      This deficiency is believed to protect against malaria because its global
      distribution is similar. However, this genetic disorder may be associated with
      potential hemolytic anemia after treatment with anti-malarials, primaquine or
      other 8-aminoquinolines. Although primaquine is used for malaria prevention, no
      study has previously investigated the prevalence of G6PD variants and G6PD
      deficiency in the Republic of Korea (ROK). METHODS: Two commercialized test kits
      (Trinity G-6-PDH and CareStart G6PD test) were used for G6PD deficiency
      screening. The seven common G6PD variants were investigated by DiaPlexC kit in
      blood samples obtained living in vivax malaria endemic regions in the ROK.
      RESULTS: Of 1,044 blood samples tested using the CareStart G6PD test, none were
      positive for G6PD deficiency. However, a slightly elevated level of G6PD activity
      was observed in 14 of 1,031 samples tested with the Trinity G-6-PDH test. Forty
      nine of the 298 samples with non-specific amplification by DiaPlexC kit were
      confirmed by sequencing to be negative for the G6PD variants. CONCLUSIONS: No
      G6PD deficiency was observed using phenotypic- or genetic-based tests in
      individuals residing in vivax malaria endemic regions in the ROK. Because massive
      chemoprophylaxis using primaquine has been performed in the ROK military to kill
      hypnozoites responsible for relapse and latent stage vivax malaria, further
      regular monitoring is essential for the safe administration of primaquine.

PMID- 24853875
TI  - Protein content analysis and antimicrobial activity of the crude venom of
      Montivipera bornmuelleri; a viper from Lebanon.
AB  - Viperidae snakes venoms represent a source of efficient bioactive components that
      have already led to the development of several new drugs. In this work, we
      analyzed the protein content of the Montivipera bornmuelleri crude venom using LC
      ESI-MS, sephadex G-75 gel filtration and SDS-PAGE and demonstrated the presence
      of proteins with molecular masses corresponding to metalloprotease III, serine
      protease and PLA2 in three fractions collected after gel filtration. Equally, we
      examined the antimicrobial effect of the venom that showed an important potency,
      as bactericidal agent, based on MBC and MIC values obtained, against
      Staphylococcus aureus and Morganella morganii bacteria. However, no activity was
      registered against Enterococcus faecalis, being the most resistant bacteria,
      neither against Aspergillus flavus and Penicillium digitatum fungal. Furthermore,
      on eleven other bacterial strains and the Candida albicans fungus, the venom has
      shown an intermediate efficacy by slightly reducing the growth. Our data
      concerning the Montivipera bornmuelleri venom give evidence of a rich and complex
      content aiding the exploration of new bioactive molecules for biopharmaceuticals
      purposes. 

PMID- 24853876
TI  - Bacteriocins active against multi-resistant gram negative bacteria implicated in
      nosocomial infections.
AB  - Multiresistant Gram-negative bacteria are the prime mover of nosocomial
      infections. Some are naturally resistant to antibiotics, their genetic makes them
      insensitive to certain families of antibiotics and they transmit these resistors
      to their offspring. Moreover, when bacteria are subjected to antibiotics, they
      eventually develop resistance against drugs to which they were previously
      sensitive. In recent years, many bacteriocins active against gram-negative
      bacteria have been identified proving their efficacy in treating infections.
      While further investigation remains necessary before the possibilities for
      bacteriocins in clinical practice can be described more fully, this review
      provides an overview of bacteriocins acting on the most common infectious gram
      negative bacteria (Klebsiella, Acinetobacter, Pseudomonas aeruginosa and E.
      coli). 

PMID- 24853878
TI  - Lysosomal storage diseases: Stem cell-based cell- and gene-therapy.
AB  - Lysosomal storage diseases (LSDs) are caused by inborn genetic defects and most
      affected babies show pathology in the CNS. LSDs are caused by a specific
      inherited enzyme deficiency that results in accumulation of substrates in the
      lysosomes, distension of the organelles and subsequent cellular malfunction.
      Currently, no effective treatment is available for most of the LSDs, because the
      blood?brain barrier bars entry of enzyme preparations into the brain. Treatment
      for LSDs can be divided into those address symptoms or those address cause. At
      present, successful treatments for the LSDs are enzyme replacement therapy (ERT)
      and cell therapy. ERT is most successful in Gaucher disease and has been approved
      for Fabry disease, and mucopolysaccharidosis I (MPS I). In addition, ERT for
      Pompe disease, MPS II, MPS VI and MPS VII has been planned and awaiting approval
      for treatment. Limitations in ERT include need for life-long treatment,
      development of antibodies, and inability to cross blood brain barrier (BBB)
      resulting in failure to halt disease progression in the brain. Transplantation of
      hematopoietic stem cells (HSCs), bone marrow stem cells (BMSCs) and umbilical
      cord blood-derived stem cells (UCBSCs) offer effective but limited efficacy for
      patients suffering from Krabbe disease, MPS VII and adrenal leukodystrophy but in
      other LSDs they are ineffective. Intracranial/intracerebral transplantation of
      genetically modified stem cells as enzyme delivery system could bypass the BBB
      effectively and ensure release of therapeutically beneficial amount of enzymes to
      affected CNS lesion sites. For this reason, stem cell-based gene therapy is the
      most effective treatment for LSDs. In mouse models of LSDs, genetically modified
      neural stem cells encoding enzyme genes effectively decreased lysosomal storage,
      reduced pathology and extended life span of animals. Cell-based gene therapies
      for LSDs bridge the application of ERT and gene therapy and are important
      direction to pursue in the future.

PMID- 24853877
TI  - Clinical utility of an array comparative genomic hybridization analysis for
      Williams syndrome.
AB  - To reveal the relation between intellectual disability and the deleted intervals
      in Williams syndrome, we performed an array comparative genomic hybridization
      analysis and standardized developmental testing for 11 patients diagnosed as
      having Williams syndrome based on fluorescent in situ hybridization testing. One
      patient had a large 4.2-Mb deletion spanning distally beyond the common 1.5-Mb
      intervals observed in 10/11 patients. We formulated a linear equation describing
      the developmental age of the 10 patients with the common deletion; the
      developmental age of the patient with the 4.2-Mb deletion was significantly below
      the expectation (developmental age = 0.51 * chronological age). The large
      deletion may account for the severe intellectual disability; therefore, the use
      of array comparative genomic hybridization may provide practical information
      regarding individuals with Williams syndrome. 

PMID- 24853879
TI  - Inflammation and wound repair.
AB  - Wound repair requires the integration of complex cellular networks to restore
      tissue homeostasis. Defects in wound repair are associated with human disease
      including pyoderma gangrenosum, a heterogeneous disorder that is characterized by
      unhealed wounds and chronic inflammation of unclear etiology. Despite its
      clinical importance, there remain significant gaps in understanding how different
      types of cells communicate to integrate inflammation and wound repair. Recent
      progress in wound and regenerative biology has been gained by studying
      genetically tractable model organisms, like zebrafish, that retain the ability to
      regenerate. The optical transparency and ease of genetic manipulation make
      zebrafish an ideal model system to dissect multi-cellular and tissue level
      interactions during wound repair. The focus of this review is on recent advances
      in understanding how inflammation and wound repair are orchestrated and
      integrated to achieve wound resolution and tissue regeneration using zebrafish. 

PMID- 24853880
TI  - Utility of the trabecular bone score (TBS) in secondary osteoporosis.
AB  - Altered bone micro-architecture is an important factor in accounting for
      fragility fractures. Until recently, it has not been possible to gain information
      about skeletal microstructure in a way that is clinically feasible. Bone biopsy
      is essentially a research tool. High-resolution peripheral Quantitative Computed
      Tomography, while non-invasive, is available only sparsely throughout the world.
      The trabecular bone score (TBS) is an imaging technology adapted directly from
      the Dual Energy X-Ray Absorptiometry (DXA) image of the lumbar spine. Thus, it is
      potentially readily and widely available. In recent years, a large number of
      studies have demonstrated that TBS is significantly associated with direct
      measurements of bone micro-architecture, predicts current and future fragility
      fractures in primary osteoporosis, and may be a useful adjunct to BMD for
      fracture detection and prediction. In this review, we summarize its potential
      utility in secondary causes of osteoporosis. In some situations, like
      glucocorticoid-induced osteoporosis and in diabetes mellitus, the TBS appears to
      out-perform DXA. It also has apparent value in numerous other disorders
      associated with diminished bone health, including primary hyperparathyroidism,
      androgen-deficiency, hormone-receptor positive breast cancer treatment, chronic
      kidney disease, hemochromatosis, and autoimmune disorders like rheumatoid
      arthritis. Further research is both needed and warranted to more clearly
      establish the role of TBS in these and other disorders that adversely affect
      bone. 

PMID- 24853881
TI  - Progesterone regulation of tissue factor depends on MEK1/2 activation and
      requires the proline-rich site on progesterone receptor.
AB  - To characterize the molecular mechanism and map the response element used by
      progesterone (P) to upregulate tissue factor (TF) in breast cancer cells. TF
      expression and mRNA levels were analyzed in breast cancer ZR-75 and T47D cells,
      using Western blot and real-time PCR, respectively. Mapping of the TF promoter
      was performed using luciferase vectors. Progesterone receptor (PR) and
      specificity protein 1 (Sp1) binding to the TF promoter were analyzed by chromatin
      immuno precipitation assay. Specific or selective inhibitors were used for the
      MEK1/2 and the c-Src pathways (UO126 and PP2, respectively). TF mRNA increase
      peaks at 18 h following P treatment in ZR-75 and T47D cells. P upregulation
      occurs via a transcriptional mechanism that depends on PR and MEK1/2 activation,
      PR and Sp1 transcription factors bind to a region in the TF promoter that
      contains three Sp1 sites. TF mRNA upregulation requires an intact PR proline-rich
      site (mPRO), but it is independent from c-Src. TF upregulation by P is mediated
      by Sp1 sites in the TF promoter region. Transcriptional upregulation in breast
      cancer cells occurs via a new mechanism that requires MEK1/2 activation and the
      mPRO site but independent of c-Src activity. PR Phosphorylation at serine 294 and
      345 is not essential. 

PMID- 24853882
TI  - Stress triggers the onset and the recurrences of hyperthyroidism in patients with
      Graves' disease.
AB  - The aim of this study was to evaluate the relationship of stressful events (SE)
      with the onset and outcome of Graves' disease (GD). Over a period of 21 years, we
      enrolled 58 consecutive patients in whom at least one SE had occurred <=12 months
      before the onset of GD. Patients were treated with antithyroid drugs (ATD) for
      >=12 months and followed up for >=5 years after ATD withdrawal. We divided
      patients in three groups: REM (who reached remission; 25.9%); EXA (who
      experienced >=1 exacerbation during ATD; 10.3%); and REL (who experienced >=1
      relapse after ATD withdrawal; 63.8%). The average age at onset was similar in the
      three groups. All males aged <=25 years at GD onset relapsed at least once; no
      patient aged >=51 years at GD onset relapsed >=2 times. All patients who
      exacerbated or relapsed had at least one SE preceding each exacerbation or
      relapse. The time lag between SE and onset of GD (19.3+/-11.9 weeks) correlated
      with the age at onset (r=0.292, P=0.0002), particularly in the REL group
      (r=0.346, P=0.001). Overall, EXA and REL patients experienced more SE than REM
      patients (P=0.0002 and P=0.003, respectively). In the REL group, the overall
      number of SE was correlated with the number of relapses (r=0.486, P<0.0001).
      There exist GD patients who are prone to develop hyperthyroidism and its
      recurrences when exposed to SE. They are relatively young; the younger these
      patients are, the shorter is the time lag between SE and the onset of
      hyperthyroidism.

PMID- 24853883
TI  - Correlation of early postoperative blood glucose levels with postoperative
      complications, hospital costs, and length of hospital stay in patients with
      gastrointestinal malignancies.
AB  - Early postoperative hyperglycemia in non-diabetic patients is an important risk
      factor affecting postoperative complications and mortality. This study aimed at
      investigating the effects of early postoperative hyperglycemia on postoperative
      complications, hospital costs, and length of hospital stay in non-diabetic
      patients with gastrointestinal malignancies; data of 1,015 non-diabetic patients
      with gastrointestinal malignancies, who underwent surgical intervention between
      January 2010 and January 2012, were retrospectively evaluated. Records on fasting
      plasma glucose (FPG), liver function, and kidney function were collected before
      and one day after surgery. Correlation of early postoperative FPG levels with
      postoperative complications, hospital costs, and length of hospital stay was
      further assessed in non-diabetic patients with gastrointestinal malignancies. One
      day after surgery, FPG results were significantly increased compared to
      preoperative values. FPG levels greater than or equal to 9.13 mmol/L (or 164.34
      mg/dL) were associated with significant increases in the incidence of
      postoperative complications, length of hospital stay, and hospital costs. An
      association is shown between FPG and postoperative hyperglycemia in non-diabetic
      patients undergoing surgery for gastrointestinal malignancies. Significant
      increases in postoperative complications among these patients suggest that
      measurement of early postoperative FPG levels is critical to identify patients
      with postoperative hyperglycemia. 

PMID- 24853884
TI  - Increased low-density lipoprotein cholesterol level is associated with non
      vertebral fractures in postmenopausal women.
AB  - Although a high serum low-density lipoprotein cholesterol (LDL-C) level is an
      established risk factor for atherosclerosis, it is unclear whether it is
      associated with osteoporosis. In this study, the associations between the serum
      LDL-C level and bone mineral density (BMD), bone metabolic markers, and the
      presence of prevalent vertebral or non-vertebral fractures were examined. A total
      of 211 healthy postmenopausal women (age range, 46-80 years) who visited a
      community health center were recruited consecutively. Their radiographic and
      biochemical characteristics were collected. Prevalent vertebral and non-vertebral
      fractures were found in 49 (23.2%) and 36 (17.1%) subjects, respectively. Simple
      regression analyses showed that the serum LDL-C level was not significantly
      correlated with lumbar or femoral BMD or serum levels of total amino-terminal
      propeptide of type I collagen (PINP) or carboxy-terminal telopeptide of type I
      collagen (CTX). Logistic regression analyses adjusted for age and BMI showed that
      the increased serum LDL-C level was selected as an index affecting the presence
      of prevalent non-vertebral fractures, but not vertebral fractures. This result
      was still significant after additional adjustments for years since menopause,
      physical activity, previous cardiovascular events, bone markers, BMD, serum Ca,
      P, Cr, 25(OH)D, grip strength, tandem gait test, and use of drugs for
      hyperlipidemia [odds ratio 1.76 (1.13-2.73), p=0.012]. These findings suggest
      that a high serum LDL-C level may be a risk factor for prevalent non-vertebral
      fragility fractures independent of bone turnover, bone mass, vitamin D
      insufficiency, or frail status in postmenopausal women, and that it may be
      detrimental to bone, as well as blood vessels.

PMID- 24853885
TI  - Serum 25-hydroxyvitamin D, calcium, and calcium-regulating hormones in
      preeclamptics and controls during first day postpartum.
AB  - The evidence for a link between vitamin D and preeclampsia is conflicting. There
      is a paucity of studies reporting simultaneous 25-hydroxyvitamin D (inactive
      form) and 1,25-dihydroxyvitamin D (biologically active form). We investigated if
      levels of serum 25-hydroxyvitamin D, calcium-regulating hormones (1,25
      dihydroxyvitamin D, parathyroid hormone), and calcium differ significantly
      between preeclamptics and controls. On postpartum day one, 98 subjects (44 with
      preeclampsia, 54 controls) were recruited among women admitted to the
      postdelivery unit, and their serum 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D,
      parathyroid hormone, serum calcium, and serum albumin levels were prospectively
      measured. The majority of participants (70%) had serum 25-hydroxyvitamin D
      level<20 ng/mL; 53% had <15 ng/mL. Mean serum 25-hydroxyvitamin D level was
      similar between cases and controls (p=0.50). Mean total serum calcium adjusted
      for albumin and magnesium was similar between cases and controls (p=0.78). Mean
      serum 1,25-dihydroxyvitamin D and parathyroid hormone levels were normal, and
      there were no differences between cases and controls. The only significant
      differences found between preeclamptic cases and controls were mean body mass
      index, parity, and season of blood draw. Vitamin D levels did not differ among
      preeclamptic cases and controls.

PMID- 24853886
TI  - Metastasis to the thyroid from non-small cell carcinoma of the lung: findings in
      (18)F-FDG PET/CT study.
AB  - The incidence of thyroid metastasis from other primary malignancy is rare. In
      this case, we present the findings of (18)F-FDG PET/CT in thyroid metastasis from
      underlying non-small cell carcinoma of the lung and highlight the importance of
      tracer uptake pattern recognition within the thyroid on (18)F-FDG PET/CT study. 

PMID- 24853888
TI  - Iron stores of breastfed infants during the first year of life.
AB  - The birth iron endowment provides iron for growth in the first months of life. We
      describe the iron endowment under conditions of low dietary iron supply. Subjects
      were infants participating in a trial of Vitamin D supplementation from 1 to 9
      months. Infants were exclusively breastfed at enrollment but could receive
      complementary foods from 4 months but not formula. Plasma ferritin (PF) and
      transferrin receptor (TfR) were determined at 1, 2, 4, 5.5, 7.5, 9 and 12 months.
      At 1 month PF ranged from 38 to 752 ug/L and was only weakly related to maternal
      PF. PF declined subsequently and flattened out at 5.5 months. PF of females was
      significantly higher than PF of males except at 12 months. TfR increased with age
      and was inversely correlated with PF. PF and TfR tracked strongly until 9 months.
      Iron deficiency (PF < 10 ug/L) began to appear at 4 months and increased in
      frequency until 9 months. Infants with ID were born with low iron endowment. We
      concluded that the birth iron endowment is highly variable in size and a small
      endowment places infants at risk of iron deficiency before 6 months. Boys have
      smaller iron endowments and are at greater risk of iron deficiency than girls. 

PMID- 24853891
TI  - RNA sequencing of all transcripts and how islet beta-cells fail.

PMID- 24853887
TI  - Diet-gene interactions and PUFA metabolism: a potential contributor to health
      disparities and human diseases.
AB  - The "modern western" diet (MWD) has increased the onset and progression of
      chronic human diseases as qualitatively and quantitatively maladaptive dietary
      components give rise to obesity and destructive gene-diet interactions. There has
      been a three-fold increase in dietary levels of the omega-6 (n-6) 18 carbon
      (C18), polyunsaturated fatty acid (PUFA) linoleic acid (LA; 18:2n-6), with the
      addition of cooking oils and processed foods to the MWD. Intense debate has
      emerged regarding the impact of this increase on human health. Recent studies
      have uncovered population-related genetic variation in the LCPUFA biosynthetic
      pathway (especially within the fatty acid desaturase gene (FADS) cluster) that is
      associated with levels of circulating and tissue PUFAs and several biomarkers and
      clinical endpoints of cardiovascular disease (CVD). Importantly, populations of
      African descent have higher frequencies of variants associated with elevated
      levels of arachidonic acid (ARA), CVD biomarkers and disease endpoints.
      Additionally, nutrigenomic interactions between dietary n-6 PUFAs and variants in
      genes that encode for enzymes that mobilize and metabolize ARA to eicosanoids
      have been identified. These observations raise important questions of whether
      gene-PUFA interactions are differentially driving the risk of cardiovascular and
      other diseases in diverse populations, and contributing to health disparities,
      especially in African American populations. 

PMID- 24853889
TI  - Ultra-performance liquid chromatography tandem mass spectrometry combined with
      automated MetaboLynx analysis approach to screen the bioactive components and
      their metabolites in Wen-Xin-Formula.
AB  - Wen-Xin-Formula (WXF), a famous traditional prescription, has been widely used to
      treat myocardial ischemia syndrome for thousands of years. However, the
      constituents absorbed into blood after oral administration of WXF remain unknown.
      Here, an integrative ultra performance liquid chromatography coupled with
      electrospray ionization/quadrupole-time-of-flight mass spectrometry (UPLC-ESI-Q
      TOF-MS) combined with the MetaboLynx approach was established to investigate the
      absorbed constituents in rats after oral administration of WXF. A hyphenated
      electrospray ionization and quadrupole-time-of-flight analyzer was used for the
      determination of accurate mass of the molecule and fragment ions. With this rapid
      and automated analysis method, a total of 32 peaks were tentatively characterized
      in vivo based on MS and MS/MS data and comparison with available databasess, 26
      of which were parent components and six metabolites. These components mainly were
      ginsenosides, paeoniflorin, galloyl glucose, berberis alkaloids, phenolic,
      phenolic glycosides and unsaturated fatty acids, glucuronide products of original
      berberis alkaloids. The present study demonstrates that integrative UPLC-ESI-Q
      TOF-MS technique and MetaboLynx data processing method were successfully applied
      for the rapid discovery of potentially bioactive components and metabolites from
      WXF, and proved that the established method could help to explore the effective
      substances for further research into WXF.

PMID- 24853892
TI  - Timing is everything: implications for metabolic consequences of sleep
      restriction.

PMID- 24853893
TI  - DPP-4 inhibitors-renoprotection in diabetic nephropathy?

PMID- 24853894
TI  - Stress response signaling pathways may lead to mitochondrial biogenesis.

PMID- 24853895
TI  - Interleukin-1 antagonism: a sturdy companion for immune tolerance induction in
      type 1 diabetes?

PMID- 24853896
TI  - Physiology helps GWAS take a step closer to mechanism.

PMID- 24853897
TI  - IL-21 and IRF4: A complex partnership in immune and metabolic regulation.

PMID- 24853898
TI  - Stem cell senescence in diabetes: forgetting the sweet old memories.

PMID- 24853899
TI  - Endogenous, adipocyte-derived lipids signal the recruitment of proinflammatory
      immune cells.

PMID- 24853900
TI  - Complexity of impaired parasympathetic heart rate regulation in diabetes.

PMID- 24853901
TI  - Homeostastic model assessment and insulin sensitivity/resistance.

PMID- 24853902
TI  - How does B-cell tolerance contribute to the protective effects of diabetes
      following induced mixed chimerism in autoimmune diabetes?

PMID- 24853903
TI  - The extracellular matrix protein MAGP1 is a key regulator of adipose tissue
      remodeling during obesity.

PMID- 24853905
TI  - Cardiovascular biomarkers in preeclampsia at triage.
AB  - INTRODUCTION: To investigate the ability of cardiovascular plasma biomarkers to
      identify imminent preeclampsia (PE) among pregnant women at triage. MATERIAL AND
      METHODS: C-terminal pro-arginine vasopressin (copeptin), C-terminal pro
      endothelin-1 (CT-proET-1), mid-regional pro-adrenomedullin (MR-proADM), and mid
      regional pro-atrial natriuretic peptide (MR-proANP) were prospectively measured
      in pregnant women presenting at the obstetrical triage units of the University
      Hospitals of Basel and Zurich, Switzerland. Logistic regression and receiver
      operating characteristics (ROC) analysis was used to assess and quantify the
      predictive ability of cardiovascular biomarkers. RESULTS: Of the 147 included
      women, 27 (18.4%) were diagnosed at admission with PE. All biomarker levels were
      significantly higher in participants with PE as compared to controls. However,
      only MR-proANP, MR-proADM and CT-proET-1 were significant and independent
      predictors of PE, after taking into account the effect of various clinical
      confounders. The area under the ROC curve (AUC) was 0.62 (95% confidence interval
      0.50-0.73) for copeptin, 0.64 (0.52-0.76) for MR-proADM, 0.71 (0.61-0.82) for CT
      proET-1, and 0.83 (0.73-0.92) for MR-proANP. The combination of MR-proANP and MR
      proADM resulted in the highest diagnostic performance (AUC 0.88; 0.79-0.96).
      DISCUSSION: Assessment of the cardiovascular plasma biomarkers MR-proANP and MR
      proADM holds promise to support diagnosis of PE at triage.

PMID- 24853907
TI  - The relationship between blood pressure and sciatic nerve blood flow velocity in
      rats with insulin-treated experimental diabetes.
AB  - Peripheral nerve blood flow (NBF) does not autoregulate but, instead, responds
      passively to changes in mean arterial pressure (MAP). How this relationship is
      impacted by insulin-treated experimental diabetes (ITED) is unknown. We tested
      the hypothesis that ITED will reduce NBF across a range of MAP in Sprague Dawley
      rats. Following 10 weeks of control or ITED conditions, conscious MAP (tail-cuff)
      was measured, and under anaesthesia, the MAP (carotid artery catheter, pressure
      transducer) and NBF (Doppler ultrasound, 40 MHz) responses to sodium
      nitroprusside (60 ug/kg) and phenylephrine (12 ug/kg) infusion were recorded
      (regression equations for MAP vs NBF were created for each rodent). Thereafter,
      motor nerve conduction velocity (MNCV) and nerve vascularization (haematoxylin
      and eosin stain) were determined. Conscious MAP was higher and MNCV was lower in
      the ITED group (p < 0.01). In response to drug infusions, the DeltaMAP and
      DeltaNBF were similar between groups (p >= 0.18). Estimated conscious NBF (based
      on substituting conscious MAP values into each individual regression equation)
      was greater in the ITED group (p < 0.01). Sciatic nerve vascularization was
      similar between groups (p >= 0.50). In contrast to the hypothesis, NBF was not
      reduced across a range of MAP. In spite of increased estimated conscious NBF
      values, MNCV was reduced in rats with ITED.

PMID- 24853908
TI  - Plasma semicarbazide-sensitive amine oxidase activity in type 1 diabetes is
      related to vascular and renal function but not to glycaemia.
AB  - PURPOSE: Associations of semicarbazide-sensitive amine oxidase (SSAO) activity
      with renal and vascular function, oxidative stress, glycaemia and diabetes
      complications were determined. METHODS: Plasma SSAO activity in 94 type 1
      diabetes (T1DM) patients, including 34 with microvascular complications T1DM
      CX[+], and in 96 healthy subjects (CON) was measured by production of
      benzaldehyde using high-performance liquid chromatography (HPLC). RESULTS: SSAO
      activity (mean +/- SD) was greater in T1DM than in CON (1049 +/- 294 vs 749 +/-
      204 mU/L; p < 0.00001) and was higher in T1DM CX[+] vs complication-free DM
      subjects (1148 +/- 313 mU/L vs 982 +/- 269 mU/L; p = 0.01). In T1DM, SSAO
      activity correlated with renal dysfunction [estimated glomerular filtration rate
      (eGFR): r = -0.44; p = 0.0001; cystatin C: r = 0.47; p = 0.0001] and markers of
      inflammation [soluble vascular cell adhesion molecule-1 (sVCAM-1): r = 0.41, p =
      0.0001; soluble intercellular adhesion molecule-1 (sICAM-1): r = 0.33, p = 0.002]
      and was inversely related to small artery elasticity (SAE) (r = -0.23, p = 0.03).
      In CON, SSAO activity correlated with HbA1c (r = 0.26; p = 0.02). CONCLUSION: In
      T1DM, SSAO activity correlates with renal dysfunction, but not with glycaemia,
      and may promote vascular inflammation and be a therapeutic target.

PMID- 24853906
TI  - Normothermic donor heart perfusion: current clinical experience and the future.
AB  - Following the first successful heart transplant in 1967, more than 100,000 heart
      transplants have been carried out worldwide. These procedures have mostly relied
      on cold ischaemic preservation of the donor heart because this simple technique
      is inexpensive and relatively reliable. However, the well-known limitations of
      cold ischaemic preservation imposes significant logistical challenges to heart
      transplantation which put a ceiling on the immediate success on this life-saving
      therapy, and limits the number of donor hearts that can be safely transplanted
      annually. Although the theoretical advantages of normothermic donor heart
      perfusion have been recognised for over a century, the technology to transport
      donor hearts in this state has only been developed within the last decade. The
      Organ Care System (OCS) which is designed and manufactured by TransMedics Inc. is
      currently the only commercially available device with this capability. This
      article reviews the history of normothermic heart perfusion and the clinical
      experience with the TransMedics OCS to date. We have also attempted to speculate
      on the future possibilities of this innovative and exciting technology.

PMID- 24853909
TI  - Glucose attenuates hypoxia-induced changes in endothelial cell growth by
      inhibiting HIF-1alpha expression.
AB  - Hyperglycaemia and hypoxia play essential pathophysiological roles in diabetes.
      We determined whether hyperglycaemia influences endothelial cell growth under
      hypoxic conditions in vitro. Using a Ruskinn Invivo2 400 Hypoxia Workstation,
      bovine aortic endothelial cells (BAEC) were exposed to high glucose
      concentrations (25 mM glucose) under normoxic or hypoxic conditions before cell
      growth (balance of proliferation and apoptosis) was assessed by fluorescence
      activated cell sorting (FACS) analysis, proliferating cell nuclear antigen
      (pCNA), Bcl-xL and caspase-3 protein expression and activity. Hypoxia increased
      hypoxia response element (HRE) transactivation and induced hypoxia-inducible
      factor-1alpha (HIF-1alpha) expression when compared to normoxic controls
      concomitant with a significant decrease in cell growth. High glucose (25 mM)
      concentrations attenuated HRE transactivation and HIF-1alpha protein expression
      while concurrently reducing hypoxia-induced changes in BAEC growth. Knockdown of
      HIF-1alpha expression significantly decreased hypoxia-induced changes in growth
      and attenuated the modulatory effects of glucose. These results provide evidence
      that hypoxia-induced control of BAEC growth can be altered by the presence of
      glucose via inhibition of HIF-1alpha expression and activation.

PMID- 24853911
TI  - Repeated CT-guided percutaneous radiofrequency thermocoagulation for recurrent
      trigeminal neuralgia.
AB  - AIMS: To investigate the long-term outcomes of repeated percutaneous
      radiofrequency thermocoagulation (PRT) for recurrent trigeminal neuralgia (TN)
      patients. METHODS: Between 2002 and 2012, 33 patients with recurrent TN following
      an initial PRT procedure were retrospectively studied and underwent 43 repeated
      PRT procedures. RESULTS: The mean length of follow-up after repeated PRT was 34
      months. Pain relief was immediate in 30 patients (90.9%), and no pain relief
      occurred in 3 patients (9.1%) following a second PRT procedure. The percentage of
      patients who remained in an 'excellent' and 'good' pain relief condition (pain
      intensity <=BIN grade III) after the second PRT procedure was 75% at 1 year, 68%
      at 2 years and 68% at 5 years, and 22 of these patients (54.5%) remained
      satisfied with their pain relief during the follow-up period. Nine patients
      underwent PRT three times and 1 patient four times. The total number of patients
      who benefited from repeated PRT was 28 (84.8%). Postprocedure complications
      including masseter weakness were present in 3 patients and limited mouth opening
      affected 1 patient. No mortalities were observed during or after repeated PRT
      procedures. CONCLUSION: Repeated PRT provides long-term pain relief benefits to
      patients with recurrent TN and should be considered as an alternative treatment
      for recurrent TN.

PMID- 24853910
TI  - Pericyte dynamics during angiogenesis: new insights from new identities.
AB  - Therapies aimed at manipulating the microcirculation require the ability to
      control angiogenesis, defined as the sprouting of new capillaries from existing
      vessels. Blocking angiogenesis would be beneficial in many pathologies (e.g.
      cancer, retinopathies and rheumatoid arthritis). In others (e.g. myocardial
      infarction, stroke and hypertension), promoting angiogenesis would be desirable.
      We know that vascular pericytes elongate around endothelial cells (ECs) and are
      functionally associated with regulating vessel stabilization, vessel diameter and
      EC proliferation. During angiogenesis, bidirectional pericyte-EC signaling is
      critical for capillary sprout formation. Observations of pericytes leading
      capillary sprouts also implicate their role in EC guidance. As such, pericytes
      have recently emerged as a therapeutic target to promote or inhibit angiogenesis.
      Advancing our basic understanding of pericytes and developing pericyte-related
      therapies are challenged, like in many other fields, by questions regarding cell
      identity. This review article discusses what we know about pericyte phenotypes
      and the opportunity to advance our understanding by defining the specific
      pericyte cell populations involved in capillary sprouting.

PMID- 24853912
TI  - Quality of life and self-reported lower extremity function in adults with HIV
      related distal sensory polyneuropathy.
AB  - BACKGROUND: Distal sensory polyneuropathy (DSP) is a common complication of HIV
      disease. Its effects on quality of life (QOL) and function have not been well
      described. OBJECTIVE: The study objectives were: (1) to compare QOL and lower
      extremity function in people with HIV-related DSP and people with HIV disease who
      do not have DSP, (2) to determine the extent to which function predicts QOL, (3)
      to evaluate the agreement of 2 function scales, and (4) to describe the use of
      pain management resources. DESIGN: This was a cross-sectional survey study with
      predictive modeling and measurement tool concordant validation. METHODS: A
      demographic questionnaire, the Medical Outcomes Study HIV Health Survey, the
      Lower Extremity Functional Scale (LEFS), the Lower Limb Functional Index (LLFI),
      and a review of medical records were used. General linear modeling was used to
      assess group differences in QOL and the relationship between function and QOL.
      Bland-Altman procedures were used to assess the agreement of the LEFS and the
      LLFI. RESULTS: Usable data for analyses were available for 82 of the 94
      participants enrolled. The 67% of participants who reported DSP symptoms tended
      to be older, had HIV disease longer, and were more likely to receive disability
      benefits. Participants without DSP had better LLFI, LEFS, and physical health
      summary scores. In multivariate models, lower limb function predicted physical
      and mental health summary scores. The LLFI identified participants with a lower
      level of function more often than the LEFS. Participants with DSP were more
      likely to use medical treatment, physical therapy, and complementary or
      alternative treatments. LIMITATIONS: A sample of convenience was used; the sample
      size resulted in a low power for the mental health summary score of the Medical
      Outcomes Study HIV Health Survey. CONCLUSIONS: Quality of life and function were
      more impaired in participants with HIV disease and DSP. The LLFI was more likely
      to capture limitations in function than the LEFS. Participants with DSP reported
      more frequent use of pain management resources.

PMID- 24853913
TI  - Evaluation of the algorithm for automatic identification of the common carotid
      artery in ARTSENS.
AB  - Arterial compliance (AC) is an indicator of the risk of cardiovascular diseases
      (CVDs) and it is generally estimated by B-mode ultrasound investigation. The
      number of sonologists in low- and middle-income countries is very
      disproportionate to the extent of CVD. To bridge this gap we are developing an
      image-free CVD risk screening tool-arterial stiffness evaluation for non-invasive
      screening (ARTSENSTM) which can be operated with minimal training. ARTSENS uses a
      single element ultrasound transducer to investigate the wall dynamics of the
      common carotid artery (CCA) and subsequently measure the AC. Identification of
      the proximal and distal walls of the CCA, in the ultrasound frames, is an
      important step in the process of the measurement of AC. The image-free nature of
      ARTSENS creates some unique issues which necessitate the development of a new
      algorithm that can automatically identify the CCA from a sequence of A-mode radio
      frequency (RF) frames. We have earlier presented the concept and preliminary
      results for an algorithm that employed clues from the relative positions and
      temporal motion of CCA walls, for identifying the CCA and finding the approximate
      wall positions. In this paper, we present the detailed algorithm and its
      extensive evaluation based on simulation and clinical studies. The algorithm
      identified the wall position correctly in more than 90% of all simulated datasets
      where the signal-to-noise ratio was greater than 3 dB. The algorithm was then
      tested extensively on RF data obtained from the CCA of 30 human volunteers, where
      it successfully located the arterial walls in more than 70% of all measurements.
      The algorithm could successfully reject frames where the CCA was not present thus
      assisting the operator to place the probe correctly in the image-free system,
      ARTSENS. It was demonstrated that the algorithm can be used in real-time with few
      trade-offs which do not affect the accuracy of CCA identification. A new method
      for depth range selection that leads to significant performance improvements has
      also been demonstrated. 

PMID- 24853914
TI  - Hierarchy in Au nanocrystal ordering in supracrystals: III. Competition between
      van der Waals and dynamic processes.
AB  - Au nanocrystals coated with thiol derivatives of varying chain sizes ranging from
      C12 to C16 were produced; two different size nanocrystals have been synthesized
      (5 and 7 nm in diameter) for each coating agent. All of those specimens are
      characterized by a low size distribution (below 7%). Those Au nanocrystals were
      used as building blocks to grow larger self-assembled crystalline structures or
      supracrystals. These crystalline growths were carried out by slow and controlled
      solvent evaporation at different temperatures and under non-null partial solvent
      vapor pressure (Pt). We show that the order within the supracrystals is
      temperature-dependent when they are made of hexadecanethiol-coated gold
      nanocrystals, regardless of the size of the nanocrystals. The interparticle
      distances within the various supracrystals that were produced were determined by
      small-angle X-ray diffraction (SAXRD). We demonstrate that the interparticle
      distance is controlled not only by the presence of physisorbed thiol residues, as
      previously reported, but also, at higher temperatures, by the dynamics of the
      organic chains and the van der Waals forces involved between the metallic cores
      of the nanocrystals forming the structure. 

PMID- 24853915
TI  - A novel vanadosilicate with hexadeca-coordinated Cs(+) ions as a highly effective
      Cs(+) remover.
AB  - The effective removal of (137) Cs(+)  ions from contaminated groundwater and
      seawater and from radioactive nuclear waste solutions is crucial for public
      health and for the continuous operation of nuclear power plants. Various (137)
      Cs(+)  removers have been developed, but more effective (137) Cs(+)  removers are
      still needed. A novel microporous vanadosilicate with mixed-valence vanadium
      (V(4+) and V(5+) ) ions is now reported, which shows an excellent ability for
      Cs(+)  capture and immobilization from groundwater, seawater, and nuclear waste
      solutions. This material is superior to other known materials in terms of
      selectivity, capacity, and kinetics, and at very low Cs(+)  concentrations, it
      was found to be the most effective material for the removal of radioactive Cs(+) 
      ions under the test conditions. This novel vanadosilicate also contains hexadeca
      coordinated Cs(+)  ions, which corresponds to the highest coordination number
      ever described. 

PMID- 24853917
TI  - [Epidemiologic and clinical profile of patients at their first consultation with
      a nephrologist in Togo].
AB  - OBJECTIVES: To determine the clinical and epidemiologic profile of the source
      population of the only nephrology department in Togo, to guide the development of
      prevention. METHODS: Prospective and descriptive cross-sectional study of all
      patients seen for the first time during the year 2012 in the department of
      nephrology and hemodialysis of the Sylvanus Olympio University Hospital in Lome.
      We analyzed the following data: medical specialty of the referring medical
      professional, the reason for consultation (RFC), demographic information, and the
      initial assessment. RESULTS: In 2012, 198 new patients were seen as outpatients
      in nephrology; their mean age was 51 +/- 18 years (16-82 years), and the sex
      ratio M/F 1.5. They were referred by a general practitioner in 97 cases (49%), a
      medical assistant in 19 (9.6%), a cardiologist in 23 (11.6%), and a nurse in 12
      (6.1%); 7 (3.5%) came on their own initiative. The RFC was kidney failure for 145
      patients (73.2%), nephrotic syndrome for 10 (5%), hypertension for 11 (5.6%), and
      polycystic kidney disease for 6 (3%). Mean serum creatinine at consultation was
      90 mg/L (15-398 mg/L). Initial GFR was less than 15 mL/min for 130 patients
      (89.7%), between 15 and 30 mL/min for 9 (6.2%), and between 30 and 60 mL/min for
      6 (4.1%). CONCLUSION: Advanced-stage kidney failure is the main reason for
      nephrology consultations in Togo.

PMID- 24853916
TI  - Variation and quantification among a target set of phosphopeptides in human
      plasma by multiple reaction monitoring and SWATH-MS2 data-independent
      acquisition.
AB  - Human plasma contains proteins that reflect overall health and represents a rich
      source of proteins for identifying and understanding disease pathophysiology.
      However, few studies have investigated changes in plasma phosphoproteins. In
      addition, little is known about the normal variations in these phosphoproteins,
      especially with respect to specific sites of modification. To address these
      questions, we evaluated variability in plasma protein phosphorylation in healthy
      individuals using multiple reaction monitoring (MRM) and SWATH-MS2 data
      independent acquisition. First, we developed a discovery workflow for
      phosphopeptide enrichment from plasma and identified targets for MRM assays.
      Next, we analyzed plasma from healthy donors using an analytical workflow
      consisting of MRM and SWATH-MS2 that targeted phosphopeptides from 58 and 68
      phosphoproteins, respectively. These two methods produced similar results showing
      low variability in 13 phosphosites from 10 phosphoproteins (CVinter < 30%) and
      high interpersonal variation of 16 phosphosites from 14 phosphoproteins (CVinter
      > 30%). Moreover, these phosphopeptides originate from phosphoproteins involved
      in cellular processes governing homeostasis, immune response, cell-extracellular
      matrix interactions, lipid and sugar metabolism, and cell signaling. This limited
      assessment of technical and biological variability in phosphopeptides generated
      from plasma phosphoproteins among healthy volunteers constitutes a reference for
      future studies that target protein phosphorylation as biomarkers. 

PMID- 24853918
TI  - An improved method of genome size estimation by flow cytometry in five
      mucilaginous species of Hyacinthaceae.
AB  - The family Hyacinthaceae constitutes about 900 species of bulbous geophytes
      usually characterized by high mucilage content. Taxonomic delimitation of
      Hyacinthaceae has been controversial since the time of Linnaeus due to the
      absence of reliable discriminating characters. Pattern of genome size variation
      can thus be considered as an added character to aid intergeneric and intrageneric
      relationship of the group. However, reports on genome size estimation by flow
      cytometric analysis of these plants are rare due to the presence of mucilage,
      which causes problem with nuclei sample preparation. To overcome this problem
      five reported nuclei isolation buffers were tested in Drimia indica of which
      Galbraith's buffer gave comparatively better results and was further modified by
      increasing pH, detergent concentration, and replacing sodium citrate by citric
      acid. The modified buffer enabled better sample preparation with increased yield,
      lesser debris, and improved DNA peak CV. The standardized buffer was used to
      estimate the 2C values of Drimia indica, Drimia nagarjunae, Drimia wightii,
      Drimia coromandeliana, and Ledebouria revoluta for the first time by flow
      cytometric analysis. This study also opens up the scope for further improvement
      in sample preparation for flow cytometric analysis of mucilaginous plants, which
      is otherwise problematic due to nuclei clumping and increased viscosity of
      sample.

PMID- 24853919
TI  - Efficacy of Australian red-back spider (Latrodectus hasselti) antivenom in the
      treatment of clinical envenomation by the cupboard spider Steatoda capensis
      (Theridiidae).
AB  - We describe the first Steatoda capensis envenomation treated with CSL red-back
      spider antivenom (RBSAV). The patient, a 51-year-old female, developed acute
      local pain, swelling, redness, and diaphoresis in association with tender
      lymphadenopathy and hypertension. These features responded, in a dose-dependent
      manner, to RBSAV. In vitro studies confirmed that RBSAV could neutralize S.
      capensis venom at equivalent concentrations required to neutralize red-back
      spider (Latrodectus hasselti) venom. Similar data were obtained using Mexican
      Latrodectus mactans antivenom (Aracmyn(r)). Although S. capensis yielded similar
      quantities of venom protein as L. hasselti, pooled S. capensis and Steatoda
      grossa venom was more rapidly toxic to insects than either L. hasselti or
      Latrodectus tredecimguttatus venom. By contrast, both Latrodectus venoms were
      more potent than S. capensis venom in contracting rat isolated mesenteric
      arteries. Size-exclusion and anion-exchange chromatography was used to purify a
      130 kDa fraction from S. capensis venom that induced contracture and loss of
      twitch tension in chick isolated biventer cervicis nerve-muscle preparations in a
      manner similar to alpha-latrotoxin. This activity was abolished by pre-incubation
      with RBSAV. We conclude that 'steatodism' may overlap more closely with
      latrodectism than previously recognized and that this bite should be managed in
      the same way as for Australian red-back envenomation.

PMID- 24853921
TI  - Development and validation of the ankle fracture outcome of rehabilitation
      measure (A-FORM).
AB  - STUDY DESIGN: Delphi panel and cohort study. OBJECTIVE: To develop and refine a
      condition-specific, patient-reported outcome measure, the Ankle Fracture Outcome
      of Rehabilitation Measure (A-FORM), and to examine its psychometric properties,
      including factor structure, reliability, and validity, by assessing item fit with
      the Rasch model. BACKGROUND: To our knowledge, there is no patient-reported
      outcome measure specific to ankle fracture with a robust content foundation.
      METHODS: A 2-stage research design was implemented. First, a Delphi panel that
      included patients and health professionals developed the items and refined the
      item wording. Second, a cohort study (n = 45) with 2 assessment points was
      conducted to permit preliminary maximum-likelihood exploratory factor analysis
      and Rasch analysis. RESULTS: The Delphi panel reached consensus on 53 potential
      items that were carried forward to the cohort phase. From the 2 time points, 81
      questionnaires were completed and analyzed; 38 potential items were eliminated on
      account of greater than 10% missing data, factor loadings, and uniqueness. The 15
      unidimensional items retained in the scale demonstrated appropriate person and
      item reliability after (and before) removal of 1 item (anxious about footwear)
      that had a higher-than-ideal outfit statistic (1.75). The "anxious about
      footwear" item was retained in the instrument, but only the 14 items with
      acceptable infit and outfit statistics (range, 0.5-1.5) were included in the
      summary score. CONCLUSION: This investigation developed and refined the A-FORM
      (Version 1.0). The A-FORM items demonstrated favorable psychometric properties
      and are suitable for conversion to a single summary score. Further studies
      utilizing the A-FORM instrument are warranted. J Orthop Sports Phys Ther
      2014;44(7):488-499. Epub 22 May 2014. doi:10.2519/jospt.2014.4980.

PMID- 24853920
TI  - In vitro antiviral activity of Ficus carica latex against caprine herpesvirus-1.
AB  - The latex of Ficus carica Linn. (Moraceae) has been shown to possess antiviral
      properties against some human viruses. To determine the ability of F. carica
      latex (F-latex) to interfere with the infection of caprine herpesvirus-1 (CpHV-1)
      in vitro, F-latex was resuspended in culture media containing 1% ethanol and was
      tested for potential antiviral effects against CpHV-1. Titration of CpHV-1 in the
      presence or in the absence of F-latex was performed on monolayers of Madin Darby
      Bovine Kidney (MDBK) cells. Simultaneous addition of F-latex and CpHV-1 to
      monolayers of MDBK cells resulted in a significant reduction of CpHV-1 titres 3
      days post-infection and this effect was comparable to that induced by acyclovir.
      The study suggests that the F-latex is able to interfere with the replication of
      CpHV-1 in vitro on MDBK cells and future studies will determine the mechanisms
      responsible for the observed antiviral activity. 

PMID- 24853922
TI  - The relationship between history and physical examination findings and the
      outcome of electrodiagnostic testing in patients with sciatica referred to
      physical therapy.
AB  - STUDY DESIGN: Cross-sectional diagnostic accuracy study. OBJECTIVE: To
      investigate the relationship between history and physical examination findings
      and the outcome of electrodiagnostic testing in patients with sciatica referred
      to physical therapy. BACKGROUND: Electrodiagnostic testing is routinely used to
      evaluate patients with sciatica. Recent evidence suggests that the presence of
      radiculopathy identified with electrodiagnostic testing may predict better
      functional outcomes in these patients. While some patient history and physical
      examination findings have been shown to predict the presence of disc herniation
      or neurological insult, little is known about their relationship to the results
      of electrodiagnostic testing. METHODS: Electrodiagnostic testing was performed on
      38 patients with sciatica who participated in a randomized trial that compared
      different physical therapy interventions. The diagnostic gold standard was the
      presence or absence of radiculopathy, based on the results of the needle
      electromyographic examination. Diagnostic sensitivity and specificity values were
      calculated, along with corresponding likelihood ratios, for select patient
      history and physical examination variables. RESULTS: No significant relationship
      was found between select patient history and physical examination findings,
      analyzed individually or in combination, and the outcome of electrodiagnostic
      testing. Diagnostic sensitivity values ranged from 0.03 (95% confidence interval
      [CI]: 0.00, 0.24) to a high of 0.95 (95% CI: 0.72, 0.99), and specificity values
      ranged from 0.10 (95% CI: 0.02, 0.34) to a high of 0.95 (95% CI: 0.72, 0.99).
      Positive likelihood ratios ranged from 0.15 (95% CI: 0.01, 2.87) to a high of
      2.33 (95% CI: 0.71, 7.70), and negative likelihood ratios ranged from 2.00 (95%
      CI: 0.35, 11.48) to a low of 0.50 (95% CI: 0.03, 8.10). CONCLUSION: In this
      investigation, the relationship between patient history and physical examination
      findings and the outcome of electrodiagnostic testing among patients with
      sciatica was not found to be statistically significant or clinically meaningful.
      However, given the small sample size and corresponding large CIs, these results
      should be considered with caution, recognizing that some of the history and
      physical examination variables may prove useful in future research. These
      findings suggest that electrodiagnostic testing is essential to identify the
      subgroup of patients with sciatica who have measurable nerve injury consistent
      with radiculopathy, which may be an important prognostic factor for recovery.
      Level of Evidence Diagnosis, level 3b-. J Orthop Sports Phys Ther 2014;44(7):508
      517. Epub 22 May 2014. doi:10.2519/jospt.2014.5002.

PMID- 24853923
TI  - Scapular kinematics pre- and post-thoracic thrust manipulation in individuals
      with and without shoulder impingement symptoms: a randomized controlled study.
AB  - STUDY DESIGN: Randomized controlled trial with immediate follow-up. OBJECTIVES:
      To evaluate the immediate effects of a low-amplitude, high-velocity thrust
      thoracic spine manipulation (TSM) on pain and scapular kinematics during
      elevation and lowering of the arm in individuals with shoulder impingement
      syndrome (SIS). The secondary objective was to evaluate the immediate effects of
      TSM on scapular kinematics during elevation and lowering of the arm in
      individuals without symptoms. BACKGROUND: Considering the regional
      interdependence among the shoulder and the thoracic and cervical spines, TSM may
      improve pain and function in individuals with SIS. Comparing individuals with SIS
      to those without shoulder pathology may provide information on the effects of TSM
      specifically in those with SIS. METHODS: Fifty subjects (mean +/- SD age, 31.8 +/
      10.9 years) with SIS and 47 subjects (age, 25.8 +/- 5.0 years) asymptomatic for
      shoulder dysfunction were randomly assigned to 1 of 2 interventions: TSM or a
      sham intervention. Scapular kinematics were analyzed during elevation and
      lowering of the arm in the sagittal plane, and a numeric pain rating scale was
      used to assess shoulder pain during arm movement at preintervention and
      postintervention. RESULTS: For those in the SIS group, shoulder pain was reduced
      immediately after TSM and the sham intervention (mean +/- SD preintervention, 2.9
      +/- 2.5; postintervention, 2.3 +/- 2.5; P<.01; moderate effect size [Cohen d =
      0.2]). Scapular internal rotation increased 0.5 degrees  +/- 0.02 degrees  (P =
      .04; small effect size [Cohen d<0.1]) during elevation of the arm after TSM and
      sham intervention in the SIS group only. Subjects with and without SIS who
      received TSM and asymptomatic subjects who received the sham intervention had a
      significant increase (1.6 degrees  +/- 2.7 degrees ) in scapular upward rotation
      postintervention (P<.05; small effect size [Cohen d<0.2]), which was not
      considered clinically significant. Scapular anterior tilt increased 1.0 degrees 
      +/- 4.8 degrees  during elevation and lowering of the arm postmanipulation
      (P<.05; small effect size [Cohen d<0.2]) in the asymptomatic subjects who
      received TSM. CONCLUSION: Shoulder pain in individuals with SIS immediately
      decreased after a TSM. The observed changes in scapular kinematics following TSM
      were not considered clinically important. LEVEL OF EVIDENCE: Therapy, level 4. J
      Orthop Sports Phys Ther 2014;44(7):475-487. Epub 22 May 2014.
      doi:10.2519/jospt.2014.4760.

PMID- 24853924
TI  - Comment on 'Why do we do the same things so differently?'.

PMID- 24853925
TI  - Experimental determination of invasive fitness in Caenorhabditis elegans.
AB  - Estimation of fitness is a key step in experimental evolution studies. However,
      no established methods currently exist to specifically estimate how successful
      new alleles are in invading populations. The main reason is that most assays do
      not accurately reflect the randomness associated with the first stages of the
      invasion, when invaders are rare and extinctions are frequent. In this protocol,
      I describe how such experiments can be done in an effective way. By using the
      nematode model, Caenorhabditis elegans, a large number of invasion experiments
      are set up, whereby invading individuals carrying a visual marker are introduced
      into populations in very low numbers. The number of invaders counted in
      consecutive generations, together with the number of extinctions, is then used in
      the context of individual-based computer simulations to provide likelihood (Lk)
      estimates for fitness. This protocol can take up to five generations of
      experimental invasions and a few hours of computer processing time. 

PMID- 24853926
TI  - Complementary X-ray tomography techniques for histology-validated 3D imaging of
      soft and hard tissues using plaque-containing blood vessels as examples.
AB  - A key problem in X-ray computed tomography is choosing photon energies for
      postmortem specimens containing both soft and hard tissues. Increasing X-ray
      energy reduces image artifacts from highly absorbing hard tissues including
      plaque, but it simultaneously decreases contrast in soft tissues including the
      endothelium. Therefore, identifying the lumen within plaque-containing vessels is
      challenging. Destructive histology, the gold standard for tissue evaluation,
      reaches submicron resolution in two dimensions, whereas slice thickness limits
      spatial resolution in the third. We present a protocol to systematically analyze
      heterogeneous tissues containing weakly and highly absorbing components in the
      original wet state, postmortem. Taking the example of atherosclerotic human
      coronary arteries, the successively acquired 3D data of benchtop and synchrotron
      radiation-based tomography are validated by histology. The entire protocol
      requires ~20 working days, enables differentiation between plaque, muscle and fat
      tissues without using contrast agents and permits blood flow simulations in
      vessels with plaque-induced constrictions. 

PMID- 24853927
TI  - Bayesian deconvolution and quantification of metabolites in complex 1D NMR
      spectra using BATMAN.
AB  - Data processing for 1D NMR spectra is a key bottleneck for metabolomic and other
      complex-mixture studies, particularly where quantitative data on individual
      metabolites are required. We present a protocol for automated metabolite
      deconvolution and quantification from complex NMR spectra by using the Bayesian
      automated metabolite analyzer for NMR (BATMAN) R package. BATMAN models
      resonances on the basis of a user-controllable set of templates, each of which
      specifies the chemical shifts, J-couplings and relative peak intensities for a
      single metabolite. Peaks are allowed to shift position slightly between spectra,
      and peak widths are allowed to vary by user-specified amounts. NMR signals not
      captured by the templates are modeled non-parametrically by using wavelets. The
      protocol covers setting up user template libraries, optimizing algorithmic input
      parameters, improving prior information on peak positions, quality control and
      evaluation of outputs. The outputs include relative concentration estimates for
      named metabolites together with associated Bayesian uncertainty estimates, as
      well as the fit of the remainder of the spectrum using wavelets. Graphical
      diagnostics allow the user to examine the quality of the fit for multiple spectra
      simultaneously. This approach offers a workflow to analyze large numbers of
      spectra and is expected to be useful in a wide range of metabolomics studies. 

PMID- 24853928
TI  - Motif-based analysis of large nucleotide data sets using MEME-ChIP.
AB  - MEME-ChIP is a web-based tool for analyzing motifs in large DNA or RNA data sets.
      It can analyze peak regions identified by ChIP-seq, cross-linking sites
      identified by CLIP-seq and related assays, as well as sets of genomic regions
      selected using other criteria. MEME-ChIP performs de novo motif discovery, motif
      enrichment analysis, motif location analysis and motif clustering, providing a
      comprehensive picture of the DNA or RNA motifs that are enriched in the input
      sequences. MEME-ChIP performs two complementary types of de novo motif discovery:
      weight matrix-based discovery for high accuracy; and word-based discovery for
      high sensitivity. Motif enrichment analysis using DNA or RNA motifs from human,
      mouse, worm, fly and other model organisms provides even greater sensitivity.
      MEME-ChIP's interactive HTML output groups and aligns significant motifs to ease
      interpretation. This protocol takes less than 3 h, and it provides motif
      discovery approaches that are distinct and complementary to other online methods.

PMID- 24853929
TI  - Highly exposed {001} facets of titanium dioxide modified with reduced graphene
      oxide for dopamine sensing.
AB  - Titanium dioxide (TiO2) with highly exposed {001} facets was synthesized through
      a facile solvo-thermal method and its surface was decorated by using reduced
      graphene oxide (rGO) sheets. The morphology and chemical composition of the
      prepared rGO/TiO2 {001} nanocomposite were examined by using suitable
      characterization techniques. The rGO/TiO2 {001} nanocomposite was used to modify
      glassy carbon electrode (GCE), which showed higher electrocatalytic activity
      towards the oxidation of dopamine (DA) and ascorbic acid (AA), when compared to
      unmodified GCE. The differential pulse voltammetric studies revealed good
      sensitivity and selectivity nature of the rGO/TiO2 {001} nanocomposite modified
      GCE for the detection of DA in the presence of AA. The modified GCE exhibited a
      low electrochemical detection limit of 6 MUM over the linear range of 2-60 MUM.
      Overall, this work provides a simple platform for the development of GCE modified
      with rGO/TiO2 {001} nanocomposite with highly exposed {001} facets for potential
      electrochemical sensing applications. 

PMID- 24853930
TI  - Are new place representations independent of theta and path integration?
AB  - Brandon et al. (2014) show that the formation of place cell representations in
      new environments is preserved under septal inactivation, and is thus likely
      independent of the hippocampal theta rhythm and, by implication, the firing of
      entorhinal grid cells and the process of path integration.

PMID- 24853931
TI  - Silencing synapses with DREADDs.
AB  - In this issue of Neuron, Stachniak et al. (2014) determine that the chemogenetic
      silencer hM4Di-DREADD suppresses presynaptic glutamate release, and by generating
      an axon-targeted hM4Di variant they demonstrate that it can be used to locally
      silence synaptic transmission in neural circuits.

PMID- 24853932
TI  - Channeling the Central Dogma.
AB  - How do neurons and networks achieve their characteristic electrical activity,
      regulate this activity homeostatically, and yet show population variability in
      expression? In this issue of Neuron, O'Leary et al. (2014) address some of these
      thorny questions in this theoretical analysis that starts with the Central Dogma.

PMID- 24853933
TI  - Blood-brain barrier: a dual life of MFSD2A?
AB  - Two recent papers in Nature, Ben-Zvi et al. (2014) and Nguyen et al. (2014),
      report a surprising dual role for the blood-brain barrier transporter MFSD2A in
      both establishing BBB integrity and in uptake of the fatty acid DHA.

PMID- 24853934
TI  - The rising tide of tDCS in the media and academic literature.
AB  - Academic and public interest in tDCS has been fueled by strong claims of
      therapeutic and enhancement effects. We report a rising tide of tDCS coverage in
      the media, while regulatory action is lacking and ethical issues need to be
      addressed.

PMID- 24853935
TI  - Discriminative and affective touch: sensing and feeling.
AB  - The multimodal properties of the human somatosensory system continue to be
      unravelled. There is mounting evidence that one of these submodalities-touch-has
      another dimension, providing not only its well-recognized discriminative input to
      the brain, but also an affective input. It has long been recognized that touch
      plays an important role in many forms of social communication and a number of
      theories have been proposed to explain observations and beliefs about the "power
      of touch." Here, we propose that a class of low-threshold mechanosensitive C
      fibers that innervate the hairy skin represent the neurobiological substrate for
      the affective and rewarding properties of touch.

PMID- 24853937
TI  - Loss-of-function variants in schizophrenia risk and SETD1A as a candidate
      susceptibility gene.
AB  - Loss-of-function (LOF) (i.e., nonsense, splice site, and frameshift) variants
      that lead to disruption of gene function are likely to contribute to the etiology
      of neuropsychiatric disorders. Here, we perform a systematic investigation of the
      role of both de novo and inherited LOF variants in schizophrenia using exome
      sequencing data from 231 case and 34 control trios. We identify two de novo LOF
      variants in the SETD1A gene, which encodes a subunit of histone
      methyltransferase, a finding unlikely to have occurred by chance, and provide
      evidence for a more general role of chromatin regulators in schizophrenia risk.
      Transmission pattern analyses reveal that LOF variants are more likely to be
      transmitted to affected individuals than controls. This is especially true for
      private LOF variants in genes intolerant to functional genetic variation. These
      findings highlight the contribution of LOF mutations to the genetic architecture
      of schizophrenia and provide important insights into disease pathogenesis.

PMID- 24853938
TI  - A role for melanopsin in alpha retinal ganglion cells and contrast detection.
AB  - Distinct subclasses of retinal ganglion cells (RGCs) mediate vision and nonimage
      forming functions such as circadian photoentrainment. This distinction stems from
      studies that ablated melanopsin-expressing intrinsically photosensitive RGCs
      (ipRGCs) and showed deficits in nonimage-forming behaviors, but not image vision.
      However, we show that the ON alpha RGC, a conventional RGC type, is intrinsically
      photosensitive in mammals. In addition to their classical response to fast
      changes in contrast through rod/cone signaling, melanopsin expression allows ON
      alpha RGCs to signal prior light exposure and environmental luminance over long
      periods of time. Consistent with the high contrast sensitivity of ON alpha RGCs,
      mice lacking either melanopsin or ON alpha RGCs have behavioral deficits in
      contrast sensitivity. These findings indicate a surprising role for melanopsin
      and ipRGCs in vision.

PMID- 24853936
TI  - The intersection of amyloid beta and tau at synapses in Alzheimer's disease.
AB  - The collapse of neural networks important for memory and cognition, including
      death of neurons and degeneration of synapses, causes the debilitating dementia
      associated with Alzheimer's disease (AD). We suggest that synaptic changes are
      central to the disease process. Amyloid beta and tau form fibrillar lesions that
      are the classical hallmarks of AD. Recent data indicate that both molecules may
      have normal roles at the synapse, and that the accumulation of soluble toxic
      forms of the proteins at the synapse may be on the critical path to
      neurodegeneration. Further, the march of neurofibrillary tangles through brain
      circuits appears to take advantage of recently described mechanisms of
      transsynaptic spread of pathological forms of tau. These two key phenomena,
      synapse loss and the spread of pathology through the brain via synapses, make it
      critical to understand the physiological and pathological roles of amyloid beta
      and tau at the synapse. 

PMID- 24853939
TI  - New and distinct hippocampal place codes are generated in a new environment
      during septal inactivation.
AB  - The hippocampus generates distinct neural codes to disambiguate similar
      experiences, a process thought to underlie episodic memory function. Entorhinal
      grid cells provide a prominent spatial signal to hippocampus, and changes in
      their firing pattern could thus generate a distinct spatial code in each context.
      We examined whether we would preclude the emergence of new spatial
      representations in a novel environment during muscimol inactivation of the medial
      septal area, a manipulation known to disrupt theta oscillations and grid cell
      firing. We found that new, highly distinct configurations of place fields emerged
      immediately and remained stable during the septal inactivation. The new place
      code persisted when theta oscillations had recovered. Theta rhythmicity and
      feedforward input from grid cell networks were thus not required to generate new
      spatial representations in the hippocampus.

PMID- 24853940
TI  - Cell types, network homeostasis, and pathological compensation from a
      biologically plausible ion channel expression model.
AB  - How do neurons develop, control, and maintain their electrical signaling
      properties in spite of ongoing protein turnover and perturbations to activity?
      From generic assumptions about the molecular biology underlying channel
      expression, we derive a simple model and show how it encodes an "activity set
      point" in single neurons. The model generates diverse self-regulating cell types
      and relates correlations in conductance expression observed in vivo to underlying
      channel expression rates. Synaptic as well as intrinsic conductances can be
      regulated to make a self-assembling central pattern generator network; thus,
      network-level homeostasis can emerge from cell-autonomous regulation rules.
      Finally, we demonstrate that the outcome of homeostatic regulation depends on the
      complement of ion channels expressed in cells: in some cases, loss of specific
      ion channels can be compensated; in others, the homeostatic mechanism itself
      causes pathological loss of function.

PMID- 24853941
TI  - The precise temporal pattern of prehearing spontaneous activity is necessary for
      tonotopic map refinement.
AB  - Patterned spontaneous activity is a hallmark of developing sensory systems. In
      the auditory system, rhythmic bursts of spontaneous activity are generated in
      cochlear hair cells and propagated along central auditory pathways. The role of
      these activity patterns in the development of central auditory circuits has
      remained speculative. Here we demonstrate that blocking efferent cholinergic
      neurotransmission to developing hair cells in mice that lack the alpha9 subunit
      of nicotinic acetylcholine receptors (alpha9 KO mice) altered the temporal fine
      structure of spontaneous activity without changing activity levels. KO mice
      showed a severe impairment in the functional and structural sharpening of an
      inhibitory tonotopic map, as evidenced by deficits in synaptic strengthening and
      silencing of connections and an absence in axonal pruning. These results provide
      evidence that the precise temporal pattern of spontaneous activity before hearing
      onset is crucial for the establishment of precise tonotopy, the major organizing
      principle of central auditory pathways.

PMID- 24853943
TI  - Cornichon2 dictates the time course of excitatory transmission at individual
      hippocampal synapses.
AB  - Cornichon2 (CNIH2), an integral component of AMPA receptor (AMPAR) complexes in
      the mammalian brain, slows deactivation and desensitization of heterologously
      reconstituted receptor channels. Its significance in neuronal signal
      transduction, however, has remained elusive. Here we show by paired recordings
      that CNIH2-containing AMPARs dictate the slow decay of excitatory postsynaptic
      currents (EPSCs) elicited in hilar mossy cells of the hippocampus by single
      action potentials in mossy fiber boutons (MFB). Selective knockdown of CNIH2
      markedly accelerated EPSCs in individual MFB-mossy cell synapses without altering
      the EPSC amplitude. In contrast, the rapidly decaying EPSCs in synapses between
      MFBs and aspiny interneurons that lack expression of CNIH2 were unaffected by the
      protein knockdown but were slowed by virus-directed expression of CNIH2. These
      results identify CNIH2 as the molecular distinction between slow and fast EPSC
      phenotypes and show that CNIH2 influences the time course and, hence, the
      efficacy of excitatory synaptic transmission.

PMID- 24853942
TI  - The lipid kinase PIP5K1C regulates pain signaling and sensitization.
AB  - Numerous pain-producing (pronociceptive) receptors signal via
      phosphatidylinositol 4,5-bisphosphate (PIP2) hydrolysis. However, it is currently
      unknown which lipid kinases generate PIP2 in nociceptive dorsal root ganglia
      (DRG) neurons and if these kinases regulate pronociceptive receptor signaling.
      Here, we found that phosphatidylinositol 4-phosphate 5 kinase type 1C (PIP5K1C)
      is expressed at higher levels than any other PIP5K and, based on experiments with
      Pip5k1c(+/-) mice, generates at least half of all PIP2 in DRG neurons.
      Additionally, Pip5k1c haploinsufficiency reduces pronociceptive receptor
      signaling and TRPV1 sensitization in DRG neurons as well as thermal and
      mechanical hypersensitivity in mouse models of chronic pain. We identified a
      small molecule inhibitor of PIP5K1C (UNC3230) in a high-throughput screen.
      UNC3230 lowered PIP2 levels in DRG neurons and attenuated hypersensitivity when
      administered intrathecally or into the hindpaw. Our studies reveal that PIP5K1C
      regulates PIP2-dependent nociceptive signaling and suggest that PIP5K1C is a
      therapeutic target for chronic pain.

PMID- 24853944
TI  - Wide-field feedback neurons dynamically tune early visual processing.
AB  - An important strategy for efficient neural coding is to match the range of
      cellular responses to the distribution of relevant input signals. However, the
      structure and relevance of sensory signals depend on behavioral state. Here, we
      show that behavior modifies neural activity at the earliest stages of fly vision.
      We describe a class of wide-field neurons that provide feedback to the most
      peripheral layer of the Drosophila visual system, the lamina. Using in vivo patch
      clamp electrophysiology, we found that lamina wide-field neurons respond to low
      frequency luminance fluctuations. Recordings in flying flies revealed that the
      gain and frequency tuning of wide-field neurons change during flight, and that
      these effects are mimicked by the neuromodulator octopamine. Genetically
      silencing wide-field neurons increased behavioral responses to slow-motion
      stimuli. Together, these findings identify a cell type that is gated by behavior
      to enhance neural coding by subtracting low-frequency signals from the inputs to
      motion detection circuits.

PMID- 24853947
TI  - Significant influence of coligands toward varying coordination modes of 2,2'
      bipyridine-3,3'-diol in ruthenium complexes.
AB  - The varying coordination modes of the ambidentate ligand 2,2'-bipyridine-3,3'
      diol (H2L) in a set of ruthenium complexes were demonstrated with special
      reference to the electronic features of the coligands, including sigma-donating
      acac(-) (= acetylacetonate) in Ru(III)(acac)2(HL(-)) (1), strongly pi-accepting
      pap (= 2-phenylazopyridine) in Ru(II)(pap)2(L(2-)) (2)/[(pap)2Ru(II)(MU-L(2
      ))Ru(II)(pap)2](ClO4)2 ([4](ClO4)2), and reported moderately pi-accepting bpy (=
      2,2'-bypiridine) in [Ru(II)(bpy)2(HL(-))]PF6 ([5]PF6)/[(bpy)2Ru(MU-L(2
      ))Ru(bpy)2](PF6)2 ([7](PF6)2). The single-crystal X-ray structures reveal that,
      in paramagnetic and electron paramagnetic resonance active 1 and reported
      diamagnetic [5]PF6, nearly planar monoanionic HL(-) coordinates to the metal ion
      via the N,N donors forming a five-membered chelate ring with hydrogen-bonded O
      H...O function at the backbone of the ligand framework, as has also been reported
      in other metal complexes. However, structurally characterized diamagnetic 2
      represents O(-),O(-) bonded seven-membered chelate of fully deprotonated but
      twisted L(2-). The nonplanarity of the coordinated L(2-) in 2 does not permit the
      second metal fragment {Ru(pap)2} or {Ru(bpy)2} or {Ru(acac)2} to bind with the
      available N,N donors at the back face of L(2-). Further, the deprotonated form of
      the model ligand 2,2'-biphenol (H2L') yields Ru(II)(pap)2(L'(2-)) (3); its
      crystal structure establishes the expected O(-),O(-) bonded seven-membered
      chelate of nonplanar L'(2-) as in reported Ru(II)(bpy)2(L'(2-)) (6), although
      {Ru(acac)2} metal precursor altogether fails to react with H2L'. All attempts to
      make diruthenium complex from {Ru(acac)2} and H2L failed; however, the
      corresponding {Ru(pap)2(2+)} derived dimeric [4](ClO4)2 was structurally
      characterized. It establishes the symmetric N,O(-)/N,O(-) bridging mode of
      nonplanar L(2-) as in reported [7](PF6)2. Besides structural and spectroscopic
      characterization of the newly developed complexes, the ligand (HL(-), L(2-), L'(2
      ), pap)-, metal-, or mixed metal-ligand-based accessible redox processes in 1(n)
      (n = +2, +1, 0, -1), 2(n)/3(n) (n = +2, +1, 0, -1, -2), and 4(n) (n = +4, +3, +2,
      +1, 0, -1) were analyzed in conjunction with density functional theory
      calculations. 

PMID- 24853946
TI  - Dendritic spikes induce ripples in parvalbumin interneurons during hippocampal
      sharp waves.
AB  - Sharp-wave ripples are transient oscillatory events in the hippocampus that are
      associated with the reactivation of neuronal ensembles within specific circuits
      during memory formation. Fast-spiking, parvalbumin-expressing interneurons (FS-PV
      INs) are thought to provide fast integration in these oscillatory circuits by
      suppressing regenerative activity in their dendrites. Here, using fast 3D two
      photon imaging and a caged glutamate, we challenge this classical view by
      demonstrating that FS-PV IN dendrites can generate propagating Ca(2+) spikes
      during sharp-wave ripples. The spikes originate from dendritic hot spots and are
      mediated dominantly by L-type Ca(2+) channels. Notably, Ca(2+) spikes were
      associated with intrinsically generated membrane potential oscillations. These
      oscillations required the activation of voltage-gated Na(+) channels, had the
      same frequency as the field potential oscillations associated with sharp-wave
      ripples, and controlled the phase of action potentials. Furthermore, our results
      demonstrate that the smallest functional unit that can generate ripple-frequency
      oscillations is a segment of a dendrite. 

PMID- 24853945
TI  - Plastic corollary discharge predicts sensory consequences of movements in a
      cerebellum-like circuit.
AB  - The capacity to predict the sensory consequences of movements is critical for
      sensory, motor, and cognitive function. Though it is hypothesized that internal
      signals related to motor commands, known as corollary discharge, serve to
      generate such predictions, this process remains poorly understood at the neural
      circuit level. Here we demonstrate that neurons in the electrosensory lobe (ELL)
      of weakly electric mormyrid fish generate negative images of the sensory
      consequences of the fish's own movements based on ascending spinal corollary
      discharge signals. These results generalize previous findings describing
      mechanisms for generating negative images of the effects of the fish's
      specialized electric organ discharge (EOD) and suggest that a cerebellum-like
      circuit endowed with associative synaptic plasticity acting on corollary
      discharge can solve the complex and ubiquitous problem of predicting sensory
      consequences of movements.

PMID- 24853949
TI  - Physicochemical modifications of histones and their impact on epigenomics.
AB  - The study of histone post-translational modifications (PTMs) has made
      extraordinary progress over the past few years and many epigenetic modifications
      have been identified and found to be associated with fundamental biological
      processes and pathological conditions. Most histone-modifying enzymes produce
      specific covalent modifications on histone tails that, taken together, elicit
      complex and concerted processes. An even higher level of complexity is generated
      by the action of small molecules that are able to modulate pharmacologically
      epigenetic enzymes and interfere with these biochemical mechanisms. In this
      article, we provide an overview of histone PTMs by reviewing and discussing them
      in terms of their physicochemical properties, emphasizing these concepts in view
      of recent research efforts to elucidate epigenetic mechanisms and devise future
      epigenetic drugs. 

PMID- 24853950
TI  - Three dimensional human small intestine models for ADME-Tox studies.
AB  - In vitro human small intestine models play a crucial part in preclinical drug
      development. Although conventional 2D systems possess many advantages, such as
      facile accessibility and high-throughput capability, they can also provide
      misleading results due to their relatively poor recapitulation of in vivo
      physiology. Significant progress has recently been made in developing 3D human
      small intestine models, suggesting that more-reliable preclinical results could
      be obtained by recreating the 3D intestinal microenvironment in vitro. Although
      there are still many challenges, 3D human small intestine models have the
      potential to facilitate drug screening and drug development. 

PMID- 24853948
TI  - Genome-wide investigation of regional blood-based DNA methylation adjusted for
      complete blood counts implicates BNC2 in ovarian cancer.
AB  - Due to its potential as a biomarker for early cancer detection, blood-based DNA
      methylation (DNAm) is of interest in cancer research. Specifically, highly
      predictive mechanisms for early detection of epithelial ovarian cancer (EOC) are
      desired, so previous studies have compared DNAm between EOC cases and controls.
      However, case-control studies are confounded by the distribution of white blood
      cell types through an immune response induced by the cancer. Rather than
      determining the distribution of the cell types manually or investigating isolated
      cell types, an alternative approach involves the use of complete blood count
      (CBC), which is routinely collected. In the analysis of an EOC case-control study
      of DNAm, we incorporate CBC measures to adjust for this confounding and compare
      DNAm between 242 EOC cases and 181 age-matched controls (assayed on the Illumina
      Infinium HumanMethylation27 or HumanMethylation450 Beadchips), at both the
      individual CpG and CpG island levels. We found that adjustment for leukocyte
      distribution using CBC measurements dramatically reduced confounding, with 62
      single CpG sites found to be associated with EOC status after adjustment (P < 5E
      8). Additionally, regional DNAm was assessed by applying principal components
      analysis to CpG islands. The top associated CpG island (P = 7E-6) was located in
      the promoter/transcription start site of the human basonuclin 2 gene (BNC2), a
      known susceptibility gene for EOC risk identified through GWAS. Follow-up studies
      are necessary to establish the role of BNC2 in blood-based DNA and EOC, including
      prospective studies to validate this region as a potential biomarker and
      predictor of EOC susceptibility. 

PMID- 24853951
TI  - The potential role of impaired Notch signalling in atopic dermatitis.
AB  - This review presents recent evidence of impaired Notch signalling in atopic
      dermatitis (AD), which is proposed to represent the "a-topic" defect linking both
      epidermal and immunological barrier dysfunctions in AD. AD epidermis exhibits a
      marked deficiency of Notch receptors. Mouse models with genetically suppressed
      Notch signalling exhibit dry skin, signs of scratching, skin barrier
      abnormalities, increased transepidermal water loss and TH2 cell-mediated
      immunological changes closely resembling human AD. Notch signals are critically
      involved in the differentiation of regulatory T cells, in the feedback inhibition
      of activated innate immunity, in late epidermal differentiation associated with
      filaggrin- and stratum corneum barrier lipid processing. Most importantly, Notch
      deficiency induces keratinocyte-mediated release of thymic stromal lymphopoietin
      (TSLP). TSLP promotes TH2 cell-driven immune responses associated with enhanced
      production of interleukin (IL)-4 and IL-31. Both TSLP and IL-31 stimulate sensory
      cutaneous neurons involved in the induction of itch. Notably, Notch1 is a
      repressor of activator protein-1 (AP-1), which is upregulated in AD epidermis.
      Without Notch-mediated suppression of AP-1 this transcription factor promotes
      excess expression of TH2 cell-related cytokines. Impaired Notch signalling
      negatively affects the homeostasis of aquaporin 3 and of the tight junction
      component claudin-1, thus explains disturbed skin barrier function with increased
      transepidermal water loss and Staphylococcus aureus colonisation as well as
      increased cutaneous susceptibility for viral infections. Thus, accumulating
      evidence links deficient Notch signalling to key pathological features of AD. 

PMID- 24853952
TI  - Linking SOX10 to a slow-growth resistance phenotype.
AB  - Slow-cycling BRAF melanoma cells are notoriously resistant to standard
      chemotherapy or targeted therapy but the underlying mechanism remains elusive.
      Now a new study unlocks this mystery and offers novel insights into developing
      more effective therapeutic interventions. 

PMID- 24853954
TI  - Lis1 is required for the expansion of hematopoietic stem cells in the fetal
      liver.

PMID- 24853953
TI  - Atg7 is required for acrosome biogenesis during spermatogenesis in mice.
AB  - The acrosome is a specialized organelle that covers the anterior part of the
      sperm nucleus and plays an essential role in the process of fertilization. The
      molecular mechanism underlying the biogenesis of this lysosome-related organelle
      (LRO) is still largely unknown. Here, we show that germ cell-specific Atg7
      knockout mice were infertile due to a defect in acrosome biogenesis and displayed
      a phenotype similar to human globozoospermia; this reproductive defect was
      successfully rescued by intracytoplasmic sperm injections. Furthermore, the
      depletion of Atg7 in germ cells did not affect the early stages of development of
      germ cells, but at later stages of spermatogenesis, the proacrosomal vesicles
      failed to fuse into a single acrosomal vesicle during the Golgi phase, which
      finally resulted in irregular or nearly round-headed spermatozoa. Autophagic flux
      was disrupted in Atg7-depleted germ cells, finally leading to the failure of LC3
      conjugation to Golgi apparatus-derived vesicles. In addition, Atg7 partially
      regulated another globozoospermia-related protein, Golgi-associated PDZ- and
      coiled-coil motif-containing protein (GOPC), during acrosome biogenesis. Finally,
      the injection of either autophagy or lysosome inhibitors into testis resulted in
      a similar phenotype to that of germ cell-specific Atg7-knockout mice. Altogether,
      our results uncover a new role for Atg7 in the biogenesis of the acrosome, and we
      provide evidence to support the autolysosome origination hypothesis for the
      acrosome. 

PMID- 24853955
TI  - Notching up vascular regeneration.
AB  - Regenerative medicine for cardiovascular disease requires effective approaches
      for therapeutic revascularization. In a recent paper in Cell Research, Sahara et
      al. establish a new role for Notch signaling to promote endothelial progenitor
      differentiation, and develop a protocol based on Notch inhibition in endothelial
      progenitors to markedly enhance the yield and purity of functional endothelial
      cells differentiated from embryonic stem cells. 

PMID- 24853956
TI  - Bis(2-quinolylmethyl)ethylenediaminediacetic acids (BQENDAs), TQEN-EDTA hybrid
      molecules as fluorescent zinc sensors.
AB  - Molecular hybrids of TQEN (N,N,N',N'-tetrakis(2-quinolylmethyl)ethylenediamine)
      and EDTA (ethylenediamine-N,N,N',N'-tetraacetic acid) were examined as
      fluorescent Zn(2+) sensors. Upon the addition of Zn(2+), N,N-BQENDA (N,N-bis(2
      quinolylmethyl)ethylenediamine-N',N'-diacetic acid, 1a) exhibits a 30-fold
      emission enhancement at 456 nm (lambdaex = 315 nm, phiZn = 0.018) in buffer
      (HEPES, pH = 7.5, 100 mM KCl). The fluorescence enhancement is Zn(2+)-specific as
      Cd(2+) induces much smaller increases (ICd/I0 = 5 and ICd/IZn = 16%). These
      spectroscopic properties, as well as the excellent water-solubility, represent a
      significant improvement compared to the parent TQEN sensor (phiZn = 0.007,
      ICd/IZn = 64%). The isoquinoline analog N,N-1-isoBQENDA (N,N-bis(1
      isoquinolylmethyl)ethylenediamine-N',N'-diacetic acid, 1b) possesses a similar
      Zn(2+) fluorescence response to the parent 1-isoTQEN (N,N,N',N'-tetrakis(1
      isoquinolylmethyl)ethylenediamine) sensor, but exhibits diminished fluorescence
      intensity. Apo 1a and 1b extract more than 50% of the Zn(2+) from an equimolar
      amount of [Zn(TPEN)](2+) (TPEN = N,N,N',N'-tetrakis(2
      pyridylmethyl)ethylenediamine) or [Zn(EDTA)](2-), whereas TPEN and EDTA cannot
      effectively remove Zn(2+) from [Zn(1a)] and [Zn(1b)]. The reduction of steric
      crowding in [Zn(TQEN)](2+) resulting from the substitution of two quinolines with
      carboxylates enhances the interaction between the metal ion and the remaining
      quinoline nitrogen atoms. The stronger bonding interaction results in enhanced
      emission intensity, Zn(2+) selectivity and metal ion affinity. This is in
      contrast to [Zn(1-isoTQEN)](2+) where the isoquinoline-carboxylate replacement
      does not relieve any coordination distortion, therefore no significant changes in
      fluorescence or metal binding properties are observed. 

PMID- 24853957
TI  - Analysis of ADAM17 polymorphisms and susceptibility to sporadic abdominal aortic
      aneurysm.
AB  - BACKGROUND: Accumulating evidence suggests that the principal TNF-alpha
      converting enzyme, a disintegrin and metalloproteinase 17 (ADAM17), is involved
      in the development of human abdominal aortic aneurysm (AAA). However, the
      association between ADAM17 gene polymorphisms and AAA has not been explored. The
      present study was aimed to determine the association between ADAM17 promoter
      polymorphisms and AAA. METHODS: A total of 316 patients with AAA and 306 age
      matched healthy controls were enrolled in this study. Two ADAM17 promoter
      polymorphisms (rs12692386 and rs1524668) were determind. Real-time PCR was
      employed to detect the expression of ADAM17. RESULTS: Overall, there was a
      significant difference in the frequency of the genotype rs12692386 between the
      AAA and control subjects (P=0.0096). Furthermore, men with the rs12692386 AG
      genotype conferred a higher risk of developing AAA (P=0.0058). Additionally, the
      rs12692386 mutated AG genotype of ADAM17 was significantly associated with
      increased ADAM17 expression (P=0.035) and TNF-alpha production (P=0.042) in AAA
      patients. In contrast, the allele frequency of rs1524668 was not statistically
      associated with AAA. CONCLUSIONS: Our findings indicate a positive association
      between the rs12692386 polymorphism of ADAM17 and AAA. This new knowledge about
      ADAM17 identifies a role for ADAM17 in the pathophysiology of AAA and has
      important clinical implications with regard to potential therapeutics.

PMID- 24853958
TI  - Treatment of non-union of humerus diaphyseal fractures: a prospective study
      comparing interlocking nail and locking compression plate.
AB  - BACKGROUND: The aim of this prospective comparative study was to compare outcomes
      and complications of humeral diaphyseal fracture non-unions managed with humerus
      interlocking nail (HIL) and locking compression plate (LCP). MATERIALS AND
      METHODS: 40 patients with non-union of humeral diaphyseal fractures were included
      in this study and were randomly allocated in two groups; group A had 20 cases
      treated with HIL and group B had 20 cases treated with LCP. Clinico-radiological
      assessments were done for each case up to 2-year follow-up period. Primary
      outcome measures (time to fracture union, union rate) and secondary outcome
      measures (functional outcome and complication such as infection, malunion,
      delayed union, implant failure, joint stiffness and iatrogenic radial nerve
      palsy) were compared between both the groups. Disabilities of the arm, shoulder
      and hand (DASH) scoring and Steward and Hundley's scoring system were used to
      assess functional outcome of the fracture fixation. RESULTS: There was no
      significant difference (p = 0.12) in terms of mean fracture union time between
      group A (15.8 +/- 4.2 weeks) and group B (17.2 +/- 3.8 weeks). Group A had 95 %
      union rate and group B had 100 % union rate (p = 0.14). At the 2-year follow-up
      visit, there was no significant difference found between both the groups
      regarding range of motion of shoulder and elbow joint. There was no significant
      difference found in final functional outcomes between both the groups on
      comparing DASH score (p = 0.14) and Steward and Hundley's score (p = 0.08). In
      terms of complications, there was insignificant difference found between both the
      groups. CONCLUSIONS: This study concludes that both the implants can be used in
      non-union of humeral shaft fractures with good functional outcomes and acceptable
      rate of complications.

PMID- 24853959
TI  - The comparison of macroscopic and histologic healing of side-to-side (SS)
      tenorrhaphy technique and primer tendon repair in a rabbit model.
AB  - INTRODUCTION: The side-to-side (SS) tenorrhaphy technique has been used in tendon
      transfer surgery. The mechanical properties of SS tendon suture have been studied
      previously. However, the histo-pathological healing of the SS tenorrhaphy of the
      tendons is unknown. The aim of this study was to assess the gross and
      histological effects of SS tenorrhaphy in a rabbit model. MATERIALS AND METHODS:
      Twenty New Zealand rabbits were used. The extensor hallucis longus and tibialis
      anterior tendon were sewed SS at the level distal to the ankle joint. The
      patellar tendon (PT) at the same side was used as control group. A unilateral
      midline incision was made and repaired with a single suture. The animals were
      killed at the 12th week postoperatively. The histological sections were obtained
      from the side of surgery from each group. Each sample was stained with
      hematoxylene and eosin (H&E). Gross and microscopic healing was compared between
      the two groups. RESULTS: Gross examination of the control group showed complete
      healing with a thin peri-tendinous sheath formation around the suture site,
      whereas in the study group, a thick peri-tendinous sheath was formed around the
      area of the tendon-tendon anastomosis. In the control group, at the 12th week
      after surgery, the healing was almost completed in all samples. In the study
      group, a thick fibro vascular sheath has formed around the side of anastomosis.
      In all specimens few inter-digitations were observed between the tendons;however,
      the trough was still present. CONCLUSION: The result of the current study showed
      that histological healing and union of SS tenorrhaphy differ from that in primary
      tendon injury and healing. Further studies are required to clarify the healing
      stages at the tenorrhaphy site.

PMID- 24853960
TI  - Thrombophilia in patients with retinal vein occlusion: a retrospective analysis.
AB  - BACKGROUND: To assess the prevalence of thrombophilia in patients with central
      (CRVO) and branch retinal vein occlusion (BRVO). METHODS: In 139 patients with
      CRVO (n = 88) and BRVO (n = 51) and in 40 healthy controls factor VIII,
      fibrinogen, antithrombin III, protein C, protein S, activated protein C
      resistance, anticardiolipin antibodies (ACA), homocysteine, factor V Leiden,
      prothrombin G20210A and methylene tetrahydrofolate reductase (MTHFR) C677T
      mutation were assessed retrospectively. RESULTS: Elevated factor VIII activity
      and the homozygous MTHFR C677T mutation were significantly more often found in
      CRVO and BRVO cases compared to controls. Age-, gender- and C-reactive protein
      adjusted logistic regression analysis did not show a significant additive effect
      of elevated factor VIII activity on the risk of developing CRVO/BRVO. Elevated
      fibrinogen levels and ACA were significantly more often found in CRVO than
      amongst controls. No significant differences were found concerning the remaining
      variables. CONCLUSIONS: We suggest elevated fibrinogen levels, ACA and the
      homozygous MTHFR C677T mutation as potential risk factors for CRVO/BRVO.

PMID- 24853961
TI  - Alkyl chain substituted 1,9-pyrazoloanthrones exhibit prominent inhibitory effect
      on c-Jun N-terminal kinase (JNK).
AB  - N-Alkyl substituted pyrazoloanthrone derivatives were synthesized, characterized
      and tested for their in vitro inhibitory activity over c-Jun N-terminal kinase
      (JNK). Among the tested molecules, a few derivatives showed significant
      inhibitory activity against JNK with minimal off-target effect on other mitogen
      activated protein kinase (MAP kinase) family members such as MEK1/2 and MKK3,6.
      These results suggested that N-alkyl (propyl and butyl) bearing pyrazoloanthrone
      scaffolds provide promising therapeutic inhibitors for JNK in regulating
      inflammation associated disorders. 

PMID- 24853962
TI  - Solubilized delivery of paliperidone palmitate by D-alpha-tocopheryl polyethylene
      glycol 1000 succinate micelles for improved short-term psychotic management.
AB  - The objective of this work was to formulate paliperidone palmitate-loaded d-alpha
      tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS or TPGS) micelles
      for improved antipsychotic effect during short-term management of psychotic
      disorders. Vitamin E TPGS micelles containing paliperidone palmitate were
      prepared by the solvent casting method and control paliperidone palmitate
      formulations were prepared by simple sonication method. The prepared micelles and
      control paliperidone palmitate formulations were evaluated for different
      parameters. Particle sizes of prepared micelles, control paliperidone palmitate
      formulations were determined at 25  degrees C by dynamic light scattering
      technique and external surface morphology was determined by transmission electron
      microscopy analysis. The encapsulation efficiency was determined by
      spectrophotometery. In-vitro release studies of micelles and control formulations
      were carried out by dialysis bag diffusion method. The particle sizes of the
      paliperidone palmitate-loaded TPGS micelles were 26.5 nm. About 92% of drug
      encapsulation efficiency was achieved with micelles. The drug release from
      paliperidone palmitate-loaded TPGS micelles was sustained for more than 24 h with
      40% of drug release. The TPGS product, i.e. paliperidone palmitate-loaded
      micelles, resulted in nano-sized delivery, solubility enhancement and
      permeability of the micelles which provided an improved and prolonged anti
      psychotic effect in comparison to control paliperidone palmitate formulation.

PMID- 24853964
TI  - Merci Francois Jacob.

PMID- 24853963
TI  - High drug load, stable, manufacturable and bioavailable fenofibrate formulations
      in mesoporous silica: a comparison of spray drying versus solvent impregnation
      methods.
AB  - Encapsulation of drugs in mesoporous silica using co-spray drying process has
      been recently explored as potential industrial method. However, the impact of
      spray drying on manufacturability, physiochemical stability and bioavailability
      in relation to conventional drug load processes are yet to be fully investigated.
      Using a 2(3) factorial design, this study aims to investigate the effect of drug
      loading process (co-spray drying and solvent impregnation), mesoporous silica
      pore size (SBA-15, 6.5 nm and MCM-41, 2.5 nm) and percentage drug load (30% w/w
      and 50% w/w) on material properties, crystallinity, physicochemical stability,
      release profiles and bioavailability of fenofibrate (FEN) loaded into mesoporous
      silica. From the scanning electronic microscopy (SEM) images, powder X-ray
      diffraction and Differential scanning calorimetry measurements, it is indicated
      that the co-spray drying process was able to load up to 50% (w/w) FEN in
      amorphous form onto the mesoporous silica as compared to the 30% (w/w) for
      solvent impregnation. The in vitro dissolution rate of the co-spray dried
      formulations was also significantly (p = 0.044) better than solvent impregnated
      formulations at the same drug loading. Six-month accelerated stability test at 40
      degrees C/75 RH in open dish indicated excellent physical and chemical stability
      of formulations prepared by both methods. The amorphous state of FEN and the
      enhanced dissolution profiles were well preserved, and very low levels of
      degradation were detected after storage. The dog data for the three selected co
      spray-dried formulations revealed multiple fold increment in FEN bioavailability
      compared to the reference crystalline FEN. These results validate the viability
      of co-spray-dried mesoporous silica formulations with high amorphous drug load as
      potential drug delivery systems for poorly water soluble drugs.

PMID- 24853965
TI  - Francois Jacob at the cutting edge.

PMID- 24853966
TI  - Lineage stem cell lines: test tubes to build pathophysiological scenarios and
      discover therapeutic targets.

PMID- 24853968
TI  - My move from EMBL to Institut Pasteur, a tribute to Francois Jacob.

PMID- 24853967
TI  - LE PATRON: reminiscences of life with Francois Jacob.

PMID- 24853969
TI  - Francois Jacob, .... an outstanding mentor!

PMID- 24853970
TI  - Francois and "X".

PMID- 24853971
TI  - Francois Jacob--the rest of the story.

PMID- 24853972
TI  - My friend, Francois Jacob, an icon among icons.

PMID- 24853973
TI  - Well-defined nanostructured surface-imprinted polymers for highly selective
      magnetic separation of fluoroquinolones in human urine.
AB  - The construction of molecularly imprinted polymers on magnetic nanoparticles
      gives access to smart materials with dual functions of target recognition and
      magnetic separation. In this study, the superparamagnetic surface-molecularly
      imprinted nanoparticles were prepared via surface-initiated reversible addition
      fragmentation chain transfer (RAFT) polymerization using ofloxacin (OFX) as
      template for the separation of fluoroquinolones (FQs). Benefiting from the
      living/controlled nature of RAFT reaction, distinct core-shell structure was
      successfully constructed. The highly uniform nanoscale MIP layer was
      homogeneously grafted on the surface of RAFT agent TTCA modified Fe3O4@SiO2
      nanoparticles, which favors the fast mass transfer and rapid binding kinetics.
      The target binding assays demonstrate the desirable adsorption capacity and
      imprinting efficiency of Fe3O4@MIP. High selectivity of Fe3O4@MIP toward FQs
      (ofloxacin, pefloxacin, enrofloxacin, norfloxacin, and gatifloxacin) was
      exhibited by competitive binding assay. The Fe3O4@MIP nanoparticles were
      successfully applied for the direct enrichment of five FQs from human urine. The
      spiked human urine samples were determined and the recoveries ranging from 83.1
      to 103.1% were obtained with RSD of 0.8-8.2% (n = 3). This work provides a
      versatile approach for the fabrication of well-defined MIP on nanomaterials for
      the analysis of complicated biosystems. 

PMID- 24853974
TI  - Additive interactions between 1-methyl-1,2,3,4-tetrahydroisoquinoline and
      clobazam in the mouse maximal electroshock-induced tonic seizure model--an
      isobolographic analysis for parallel dose-response relationship curves.
AB  - BACKGROUND: The aim of this study was to characterize the anticonvulsant effect
      of 1-methyl-1,2,3,4-tetrahydroisoquinoline (1-MeTHIQ) in combination with
      clobazam (CLB) in the mouse maximal electroshock-induced seizure (MES) model.
      METHODS: The anticonvulsant interaction profile between 1-MeTHIQ and CLB in the
      mouse MES model was determined using an isobolographic analysis for parallel dose
      response relationship curves. RESULTS: Electroconvulsions were produced in albino
      Swiss mice by a current (sine wave, 25 mA, 500 V, 50 Hz, 0.2-second stimulus
      duration) delivered via auricular electrodes by a Hugo Sachs generator. There was
      an additive effect of the combination of 1-MeTHIQ with CLB (at the fixed ratios
      of 1:3, 1:1 and 3:1) in the mouse MES-induced tonic seizure model. CONCLUSIONS:
      The additive interaction of the combination of 1-MeTHIQ with CLB (at fixed-ratios
      of 1:3, 1:1 and 3:1) in the mouse MES model seems to be pharmacodynamic in nature
      and worth of considering in further clinical practice.

PMID- 24853975
TI  - Anticoagulant factor V: factors affecting the integration of novel scientific
      discoveries into the broader framework.
AB  - Since its initial discovery in the 1940s, factor V has long been viewed as an
      important procoagulant protein in the coagulation cascade. However, in the later
      part of the 20th century, two different scientists proposed novel anticoagulant
      roles for factor V. Philip Majerus proposed the first anticoagulant function for
      factor V in 1983, yet ultimately it was not widely accepted by the broader
      scientific community. In contrast, Bjorn Dahlback proposed a different
      anticoagulant role for factor V in 1994. While this role was initially contested,
      it was ultimately accepted and integrated into the scientific framework. In this
      paper, I present a detailed historical account of these two anticoagulant
      discoveries and propose three key reasons why Dahlback's anticoagulant role for
      factor V was accepted whereas Majerus' proposed role was largely overlooked.
      Perhaps most importantly, Dahlback's proposed anticoagulant role was of great
      clinical interest because the discovery involved the study of an important subset
      of patients with thrombophilia. Soon after Dahlback's 1994 work, this patient
      population was shown to possess the factor V Leiden mutation. Also key in the
      ultimate acceptance of the second proposed anticoagulant role was the persistence
      of the scientist who made the discovery and the interest in and ability of others
      to replicate and reinforce this work. This analysis of two different yet similar
      discoveries sheds light on factors that play an important role in how new
      discoveries are incorporated into the existing scientific framework. 

PMID- 24853976
TI  - The pediatric burden of disease from lead exposure at toxic waste sites in low
      and middle income countries.
AB  - BACKGROUND: The impact of lead from toxic waste sites on children in low and
      middle income countries has not been calculated due to a lack of exposure data.
      We sought to calculate this impact in Disability Adjusted Life Years (DALYs).
      MATERIALS AND METHODS: Using an Integrated Exposure Uptake Biokinetic (IEUBK)
      model, we converted soil and drinking water lead levels from sites in the
      Blacksmith Institute's Toxic Sites Identification Program (TSIP) into mean blood
      lead levels (BLLs). We then calculated the incidence of mild mental retardation
      (MMR) and DALYs resulting from these BLLs. RESULTS: The TSIP included 200 sites
      in 31 countries with soil (n=132) or drinking water (n=68) lead levels,
      representing 779,989 children younger than 4 years of age potentially exposed to
      lead. Environmental lead levels produced a range of BLLs from 1.56 to 104.71
      ug/dL. These BLLs equated to an estimated loss of 5.41-8.23 IQ points, resulting
      in an incidence of MMR of 6.03 per 1000 population and 76.1 DALYs per 1000
      population. DISCUSSION: Soil and water lead levels at toxic waste sites predict
      BLLs that lower the intelligence quotient (IQ), with the resulting MMR
      potentially limiting individual- and country-level development. The preventable
      burden of disease produced by these sites highlights the need for toxic waste
      sites to be systematically identified, evaluated, and remediated.

PMID- 24853979
TI  - Synthesis and ligand-based reduction chemistry of boron difluoride complexes with
      redox-active formazanate ligands.
AB  - Mono(formazanate) boron difluoride complexes (LBF2), which show remarkably facile
      and reversible ligand-based redox-chemistry, were synthesized by transmetallation
      of bis(formazanate) zinc complexes with boron trifluoride. The one-electron
      reduction product [LBF2](-)[Cp2Co](+) and a key intermediate for the
      transmetallation reaction, the six-coordinate zinc complex (L(BF3))2Zn were
      isolated and fully characterized. 

PMID- 24853978
TI  - The possible societal impact of the decrease in U.S. blood lead levels on adult
      IQ.
AB  - BACKGROUND: The dramatic decrease in U.S. blood lead levels (BLLs) since the
      1970s has been documented--however, the anticipated societal impact on
      intelligence quotient (IQ) has not. The objectives of this study were to
      determine whether mean IQs of American adults, adjusted for demographics, have
      increased in concert with society's decreasing BLL. METHODS: Mean IQs of eight
      normal adult cohorts (N=800), tested individually in 2007 by trained clinicians,
      were compared using ANCOVA and correlation analysis. Cohorts ranged in mean
      societal BLLs from 4 1/2 MUg/dL (born 1985-1987) to 19 MUg/dL (born 1963-1972).
      IQs were adjusted for confounders-education, gender, ethnicity, region, urban
      status. To control for age, we analyzed IQ data for a second adult sample
      (N=800), tested in 1995-all born when BLLs were high (1951-1975, BLL >= 15
      MUg/dL). RESULTS: When controlling for education, gender, ethnicity, and region,
      the regression of IQs on BLLs was significant (r=-0.84, p<0.01); the modeled
      change in BLLs from 20 to 4 MUg/dL suggests predicted increases of 3.8 IQ points
      (95% CI, 1.4-6.2). Also controlling for urban status produced significance (r=
      0.88, p<0.01) with predicted increases of 5.2 points (95% CI, 2.4-8.0). Control
      analyses ruled out aging as a confounder. CONCLUSIONS: The dramatic societal
      decreases in BLLs in the U.S. since the 1970s were associated with a 4-5-point
      increase in the mean IQs of Americans. This effect is consistent with
      researchers' predictions; however, other variables (e.g., medical advances) may
      have contributed to the IQ gains.

PMID- 24853977
TI  - Effect of hemoglobin adjustment on the precision of mercury concentrations in
      maternal and cord blood.
AB  - The cord-blood mercury concentration is usually considered the best biomarker in
      regard to developmental methylmercury neurotoxicity. However, the mercury
      concentration may be affected by the binding of methylmercury to hemoglobin and
      perhaps also selenium. As cord-blood mercury analyses appear to be less precise
      than suggested by laboratory quality data, we studied the interrelationships of
      mercury concentrations with hemoglobin in paired maternal and cord blood samples
      from a Faroese birth cohort (N=514) and the Mothers and Children's Environmental
      Health study in Korea (n=797). Linear regression and structural equation model
      (SEM) analyses were used to ascertain interrelationships between the exposure
      biomarkers and the possible impact of hemoglobin as well as selenium. Both
      methods showed a significant dependence of the cord-blood concentration on
      hemoglobin, also after adjustment for other exposure biomarkers. In the SEM, the
      cord blood measurement was a less imprecise indicator of the latent methylmercury
      exposure variable than other exposure biomarkers available, and the maternal hair
      concentration had the largest imprecision. Adjustment of mercury concentrations
      both in maternal and cord blood for hemoglobin improved their precision, while no
      significant effect of the selenium concentration in maternal blood was found.
      Adjustment of blood-mercury concentrations for hemoglobin is therefore
      recommended.

PMID- 24853980
TI  - Patient safety: The Agency for Healthcare Research and Quality's ongoing
      commitment.

PMID- 24853981
TI  - Enablers and barriers to implementing unit-specific nursing performance
      dashboards.

PMID- 24853982
TI  - The oldest anatomical handmade skull of the world c. 1508: 'the ugliness of
      growing old' attributed to Leonardo da Vinci.
AB  - The author discusses a previously unknown early sixteenth-century renaissance
      handmade anatomical miniature skull. The small, naturalistic skull made from an
      agate (calcedonia) stone mixture (mistioni) shows remarkable osteologic details.
      Dr. Saban was the first to link the skull to Leonardo. The three-dimensional
      perspective of and the search for the senso comune are discussed. Anatomical
      errors both in the drawings of Leonardo and this skull are presented. The article
      ends with the issue of physiognomy, his grotesque faces, the Perspective Communis
      and his experimenting c. 1508 with the stone mixture and the human skull.
      Evidence, including the Italian scale based on Crazie and Braccia, chemical
      analysis leading to a mine in Volterra and Leonardo's search for the soul in the
      skull are presented. Written references in the inventory of Salai (1524), the
      inventory of the Villa Riposo (Raffaello Borghini 1584) and Don Ambrogio Mazenta
      (1635) are reviewed. The author attributes the skull c. 1508 to Leonardo da
      Vinci. 

PMID- 24853983
TI  - Alanine transaminase as a single marker is not reliable for selecting candidates
      of pegylated interferon and ribavirin treatment.

PMID- 24853984
TI  - Hirsutenone reduces deterioration of tight junction proteins through EGFR/Akt and
      ERK1/2 pathway both converging to HO-1 induction.
AB  - Oxidative stress-induced disruption of epithelial tight junctions (TJ) plays a
      critical role in the pathogenesis of intestinal disorders, including inflammatory
      bowel disease (IBD). The current study investigated the protective effect of
      hirsutenone against disruption of the intestinal barrier in vitro and in a mouse
      model of colitis. Caco-2 cells were stimulated with tert-butyl hydroperoxide (t
      BH). Hirsutenone prevented the t-BH-induced increase in permeability by
      inhibiting the reduction in zonula occludens-1 (ZO-1) expression, and rapidly
      stimulated tyrosine phosphorylation of the epidermal growth factor receptor
      (EGFR). Hirsutenone-mediated protection against the loss of ZO-1 depends on the
      activation of both ERK1/2 and Akt signaling pathways. Interestingly, hirsutenone
      mediated activation of Akt, but not ERK1/2, signaling was EGFR-dependent.
      Hirsutenone increased heme oxygenase-1 (HO-1) expression through both EGFR/Akt-
      and ERK1/2-dependent pathways, contributing to the protective effects against TJ
      dysfunction. Colitis was induced in mice by intrarectal administration of 2,4,6,
      trinitrobenzene sulfonic acid (TNBS). Hirsutenone administration improved the
      clinical parameters and tissue histological appearance, increased HO-1
      expression, attenuated reduction of ZO-1 and occludin mRNA, and promoted BrdU
      incorporation in the colonic epithelium of TNBS-treated mice. Taken together, our
      results demonstrate that hirsutenone reverse disordered intestinal permeability
      by activating EGFR/Akt and ERK1/2 pathways, which are involved in the regulation
      of HO-1 expression. These findings highlight the potential of hirsutenone for
      clinical applications in the treatment of IBD. 

PMID- 24853986
TI  - [Intraobserver reliability of the Handball-specific complex test (HBKT)].
AB  - BACKGROUND: There are clearly no complex and sports-specific tests in handball.
      So far, no specific complex test has been developed and verified for its
      intraobserver reliability (IR). OBJECTIVE: The aim of this study was to determine
      the IR of the Handball-specific complex test (HBKT). METHODS: The HBKT was
      applied twice at an interval of two days to two teams of the German Third League
      (n = 30; age 25.7 +/- 3.9 years, range: 19 - 33 years). Within the HBKT, the
      stress parameters lactate and heart rate as well as the loading parameters time,
      throwing velocity and number of errors were collected. RESULTS: Overall, 23 %
      (3/13) of the stress parameters showed a high relative [intraclass correlation
      coefficient (ICC) > 0.75] and absolute [coefficient of variation (CV) <= 5 %] IR.
      On average, a sufficient absolute (?CV = 11.3 %) and relative (?ICC = 0.67) IR
      was observed. Without the parameters "missed throws" and "technical errors" in
      both rounds, the IR increased significantly (?ICC: from 0.67 to 0.72 & ?CV from
      11.3 to 6.3 %). The heart rate was comparatively more reliable than lactate (?ICC
      = 0.71 & ?CV = 4.23 % vs. ?ICC = 0.65 & ?CV = 15.1 %). With respect to load
      parameters in round one, 50 % (5/10) showed a high IR; in round two, these values
      decreased to 40 % (4/10). The mean IR of the parameters in round one was higher
      than in round two (?ICC = 0.71 & ?CV = 12.2 % vs. ?ICC = 0.60 & ?CV = 14.3 %).
      Overall, there was an improvement of the athletes in most stress and load
      parameters from session one to session two. CONCLUSIONS: The HBKT can be attested
      with a sufficient intraobserver reliability. When the parameters "missed throws"
      and "technical errors" were excluded, the IR further increased significantly.
      Therefore, these parameters should be recorded in order to standardized the HBKT,
      but not be included in the statistical analysis. There are discrete adaptation
      and learning effects. For this reason, it is essential to familiarise trainers
      and players with the HBKT test procedure before the first measurement. Otherwise
      training effects can be easily overrated. Moreover, the test concept of HBKT can
      be used as a blueprint for the development of sport-specific tests in other team
      sports (e. g., soccer, basketball). For example, we generated a complex soccer
      specific field test 1 based on the HBKT.

PMID- 24853994
TI  - Molecular structure, vibrational spectra (FTIR and FT Raman) and natural bond
      orbital analysis of 4-Aminomethylpiperidine: DFT study.
AB  - The FT-IR and FT-Raman spectra of 4-Aminomethylpiperidine have been recorded
      using Perkin Elmer Spectrophotometer and Nexus 670 spectrophotometer. The
      equilibrium geometrical parameters, various bonding features, the vibrational
      wavenumbers, the infrared intensities and the Raman scattering activities were
      calculated using Hartree-Fock and density functional method (B3LYP) with 6
      311+G(d,p) basis set. Detailed interpretations of the vibrational spectra have
      been carried out with the aid of the normal coordinate analysis. The
      spectroscopic and natural bonds orbital (NBO) analysis confirms the occurrence of
      intra molecular hydrogen bonds, electron delocalization and steric effects. The
      changes in electron density in the global minimum and in the energy of
      hyperconjugative interactions of 4-Aminomethylpiperidine (4AMP) were calculated.
      The theoretical UV-Visible spectrum of the compound was computed in the region
      200-400nm by time-dependent TD-DFT approach. The calculated HOMO and LUMO
      energies show that charge transfer occur within the molecule. The dipole moment
      (MU) and polarizability (alpha), anisotropy polarizability (Deltaalpha) and
      hyperpolarizability (beta) of the molecule have been reported. 

PMID- 24853985
TI  - Probing biased/partial agonism at the G protein-coupled A(2B) adenosine receptor.
AB  - G protein-coupled A(2B) adenosine receptor (AR) regulates numerous important
      physiological functions, but its activation by diverse A(2B)AR agonists is poorly
      profiled. We probed potential partial and/or biased agonism in cell lines
      expressing variable levels of endogenous or recombinant A(2B)AR. In cAMP
      accumulation assays, both 5'-substituted NECA and C2-substituted MRS3997 are full
      agonists. However, only 5'-substituted adenosine analogs are full agonists in
      calcium mobilization, ERK1/2 phosphorylation and beta-arrestin translocation.
      A(2B)AR overexpression in HEK293 cells markedly increased the agonist potency and
      maximum effect in cAMP accumulation, but less in calcium and ERK1/2. A(2B)AR
      siRNA silencing was more effective in reducing the maximum cAMP effect of non
      nucleoside agonist BAY60-6583 than NECA's. A quantitative 'operational model'
      characterized C2-substituted MRS3997 as either balanced (cAMP accumulation,
      ERK1/2) or strongly biased agonist (against calcium, beta-arrestin). N6
      substitution biased against ERK1/2 (weakly) and calcium and beta-arrestin
      (strongly) pathways. BAY60-6583 is ERK1/2-biased, suggesting a mechanism distinct
      from adenosine derivatives. BAY60-6583, as A(2B)AR antagonist in MIN-6 mouse
      pancreatic beta cells expressing low A(2B)AR levels, induced insulin release.
      This is the first relatively systematic study of structure-efficacy relationships
      of this emerging drug target.

PMID- 24853995
TI  - Three-year stability of cardiovascular and autonomic nervous system responses to
      psychological stress.
AB  - Chronically heightened physiological reactivity to or delayed recovery from
      stress may contribute to cardiovascular (CV) risk and mortality. Long-term
      stability of physiological stress responses has received little attention. Our
      objectives were to evaluate the 3-year stability of reactivity and recovery
      change scores across CV and autonomic parameters and assess whether sex and age
      moderate stability. A total of 134 healthy participants underwent two laboratory
      stress protocols, including four 5-min interpersonal stressors, each followed by
      a 5-min recovery period. Heart rate (HR), blood pressure (BP), and HR variability
      (high frequency, low frequency, very low frequency [VLF]) were obtained. Spearman
      rank correlations and linear regressions were performed. Significant correlations
      emerged for all physiological measures except diastolic BP and VLF recovery. No
      significant sex or age differences were found. Stress responses represent stable
      individual traits little affected by sex or age. 

PMID- 24853997
TI  - Ocular findings in 87 adults with Ghent-1 verified Marfan syndrome.
AB  - PURPOSE: To study ocular characteristics in 87 patients with verified Marfan
      syndrome (MFS) based on the Ghent criteria from 1996 (Ghent-1). METHODS: The
      position of the lens was noted by observing the eye in different gaze directions
      in maximal mydriasis during slit lamp examination. Ectopia lentis (EL) was
      classified as subluxated (dislocation slightly backwards) or luxated (vertical or
      horizontal displacement). Corneal curvature, axial length (AL), corneal diameter,
      central corneal thickness, anterior chamber depth, lens thickness, condition of
      the iris, intraocular pressure, spherical equivalent and visual acuity were also
      investigated. RESULTS: EL was found in 108 eyes (62.1%). Of the 68 phakic eyes
      with EL, 43 (63.2%) had subluxation. Mean AL was 24.80 +/- 2.57 mm, and the AL
      was above 23.5 mm in 65.3%. Mean keratometry (K) in phakic eyes was 41.79 +/-
      1.70 diopters (D), and the K value was <41.5D in 46.8%. Iris hypoplasia was found
      in 3.4%. Myopia above 3D occurred in 38.4% of the phakic eyes. Mean binocular
      logMAR was 0.10 +/- 0.32. Only five patients (5.7%) had a logMAR more than 0.5.
      These 5 patients had EL, and 4 of them were amblyopic. CONCLUSION: In this
      strictly defined MFS group fulfilling the Ghent-1 criteria, the prevalence of EL
      was 62.1%. In many cases, the dislocation of the lens was subtle. On average, the
      corneas were flattened and the globe length was increased. Only a few patients
      were visually impaired. Children with MFS should have a thorough follow up to
      avoid amblyopia.

PMID- 24853996
TI  - Targeted discovery and validation of plasma biomarkers of Parkinson's disease.
AB  - Despite extensive research, an unmet need remains for protein biomarkers of
      Parkinson's disease (PD) in peripheral body fluids, especially blood, which is
      easily accessible clinically. The discovery of such biomarkers is challenging,
      however, due to the enormous complexity and huge dynamic range of human blood
      proteins, which are derived from nearly all organ systems, with those originating
      specifically from the central nervous system (CNS) being exceptionally low in
      abundance. In this investigation of a relatively large cohort (~300 subjects),
      selected reaction monitoring (SRM) assays (a targeted approach) were used to
      probe plasma peptides derived from glycoproteins previously found to be altered
      in the CNS based on PD diagnosis or severity. Next, the detected peptides were
      interrogated for their diagnostic sensitivity and specificity as well as the
      correlation with PD severity, as determined by the Unified Parkinson's Disease
      Rating Scale (UPDRS). The results revealed that 12 of the 50 candidate
      glycopeptides were reliably and consistently identified in plasma samples, with
      three of them displaying significant differences among diagnostic groups. A
      combination of four peptides (derived from PRNP, HSPG2, MEGF8, and NCAM1)
      provided an overall area under curve (AUC) of 0.753 (sensitivity: 90.4%;
      specificity: 50.0%). Additionally, combining two peptides (derived from MEGF8 and
      ICAM1) yielded significant correlation with PD severity, that is, UPDRS (r =
      0.293, p = 0.004). The significance of these results is at least two-fold: (1) it
      is possible to use a targeted approach to identify otherwise very difficult to
      detect CNS related biomarkers in peripheral blood and (2) the novel biomarkers,
      if validated in independent cohorts, can be employed to assist with clinical
      diagnosis of PD as well as monitoring disease progression. 

PMID- 24853998
TI  - Monocyte count/HDL cholesterol ratio and cardiovascular events in patients with
      chronic kidney disease.
AB  - BACKGROUND AND AIM: Previous studies showed that renal dysfunction was associated
      with both a reduction in serum high-density lipoprotein (HDL) cholesterol
      concentration and increased circulating monocyte count. We aimed to investigate
      the effect of circulating monocyte to serum HDL cholesterol ratio (M/H ratio) on
      fatal and composite cardiovascular events, in an observational cohort study of
      chronic kidney disease (CKD) patients. MATERIALS AND METHODS: A total of 340
      subjects with stage 1-5 CKD were followed for a mean follow-up period of 33
      (range 2-44) months and assessed for fatal and nonfatal CV events. M/H ratio was
      calculated for all patients. All-cause mortality and CVE were also analyzed in
      relation to M/H ratio. RESULTS: Monocyte/HDL cholesterol ratio was negatively
      correlated with estimated glomerular filtration rate (eGFR) (r = -0.43, P <
      0.001). Notably, both fatal and combined fatal and nonfatal cardiovascular events
      were more common in patients having a M/H ratio in the third tertile was
      associated with a hazard ratio of 2.24 and 4.91, respectively, for fatal and
      composite cardiovascular events compared to being in the first tertile.
      CONCLUSION: Monocyte/HDL cholesterol ratio was increased with decreasing eGFR in
      predialytic CKD patients. Most importantly, we report for the first time that an
      increased M/H ratio was cross-sectionally associated with a worse cardiovascular
      profile and arose as independent predictors of major cardiovascular events during
      follow-up.

PMID- 24853999
TI  - Different outcomes of peritoneal catheter percutaneous placement by nephrologists
      using a trocar versus the Seldinger technique: the experience of two Brazilian
      centers.
AB  - A good catheter implantation technique is important to allow effective peritoneal
      access function and long-term technique survival. Studies regarding results
      obtained by nephrologists in comparison with different techniques have been
      limited. The aim of this study was to investigate the rate of early catheter
      related complications and catheter survival in two Brazilian centers, according
      to two different percutaneous methods of catheter implantation performed by
      nephrologist team. Adult incident patients recruited from January 2006 to July
      2013 having undergone first peritoneal dialysis (PD) catheter implantation were
      included in the analysis. Mechanical and infectious early complication rates were
      defined as time to the first event occurring up to 3 months. Four hundred and
      forty-five consecutive Tenckhoff catheters were implanted by nephrologist team
      percutaneously after antibiotic prophylaxis in an operating room: trocar was used
      in 349 (78.4 %) and Seldinger technique (ST) in 99 (21.6 %). The ST was
      significantly associated with a lower rate of leak (16.3 vs 3 %, p = 0.03) and
      outflow failure due to tip catheter migration (22.6 vs 10.1 %, p = 0.04), while
      early infectious complication rates were similar between the two groups (p =
      0.59). Long-term catheter survival was higher in Seldinger group (log-rank, p =
      0.031). By Cox multivariate analysis, adjusted for age, sex, and diabetes, the ST
      remained independently associated with better catheter survival [HR 0.681 (0.462
      0.910), p = 0.04]. As conclusion, our experience showed better PD outcomes with
      the ST than trocar method of catheter implantation by nephrologist.

PMID- 24854000
TI  - Structural elements in the Gag polyprotein of feline immunodeficiency virus
      involved in Gag self-association and assembly.
AB  - The Gag polyprotein of feline immunodeficiency virus (FIV) assembles at the
      plasma membrane of the infected cells. We aimed to identify the FIV Gag domains
      that interact and promote Gag multimerization. To do this we generated a series
      of Gag subdomains and tested their ability to associate with full-length Gag and
      be recruited into extracellular virus-like particles (VLPs). Removal of 37
      residues from the C-terminus of FIV Gag and deletion of the N-terminal and
      central regions of the nucleocapsid (NC) domain attenuated but did not abrogate
      association with wild-type Gag, whereas a Gag mutant protein encompassing the
      matrix (MA) and capsid (CA) domains interacted poorly with full-length Gag.
      Association with wild-type Gag was abolished by deleting most of the NC together
      with the N-terminal 40 residues of the MA, which most likely reflects the
      inability of this Gag mutant to bind RNA. Notably, the CA-NC Gag subdomain both
      associated with wild-type Gag and was recruited into particles in a proportion
      close to 50 % of the total Gag-related protein mass of VLPs. Moreover, both a Gag
      protein lacking the C-terminal p2 peptide and a nonmyristoylated version of the
      polyprotein exhibited a transdominant-negative effect on the assembly of wild
      type Gag. Analysis of Gag mutants carrying internal deletions within the CA
      revealed that the N-terminal and the C-terminal domains of the CA are necessary
      for Gag assembly. Our results demonstrate that the FIV CA-NC region constitutes
      the principal self-interaction domain of Gag and that the RNA-binding capacity of
      Gag is necessary for its multimerization. 

PMID- 24854001
TI  - Genomic diversity in European Spodoptera exigua multiple nucleopolyhedrovirus
      isolates.
AB  - Key virus traits such as virulence and transmission strategies rely on genetic
      variation that results in functional changes in the interactions between hosts
      and viruses. Here, comparative genomic analyses of seven isolates of Spodoptera
      exigua multiple nucleopolyhedrovirus (SeMNPV) with differing phenotypes were
      employed to pinpoint candidate genes that may be involved in host-virus
      interactions. These isolates obtained after vertical or horizontal transmission
      of infection in insects differed in virulence. Apart from one genome containing a
      piggyBac transposon, all European SeMNPV isolates had a similar genome size and
      content. Complete genome analyses of single nucleotide polymorphisms and
      insertions/deletions identified mutations in 48 ORFs that could result in
      functional changes. Among these, 13 ORFs could be correlated with particular
      phenotypic characteristics of SeMNPV isolates. Mutations were found in all gene
      functional classes and most of the changes we highlighted could potentially be
      associated with differences in transmission. The regulation of DNA replication
      (helicase, lef-7) and transcription (lef-9, p47) might be important for the
      establishment of sublethal infection prior to and following vertical
      transmission. Virus-host cell interactions also appear instrumental in the
      modulation of viral transmission as significant mutations were detected in virion
      proteins involved in primary (AC150) or secondary infections (ME35) and in
      apoptosis inhibition (IAP2, AC134). Baculovirus populations naturally harbour
      high genomic variation located in genes involved at different levels of the
      complex interactions between virus and host during the course of an infection.
      The comparative analyses performed here suggest that the differences in
      baculovirus virulence and transmission phenotypes involve multiple molecular
      pathways. 

PMID- 24854002
TI  - Conserved regions of bovine adenovirus-3 pVIII contain functional domains
      involved in nuclear localization and packaging in mature infectious virions.
AB  - Adenoviruses are non-enveloped DNA viruses that replicate in the nucleus of
      infected cells. One of the core proteins, named pVIII, is a minor capsid protein
      connecting the core with the inner surface of the capsid. Here, we report the
      characterization of minor capsid protein pVIII encoded by the L6 region of bovine
      adenovirus (BAdV)-3. Anti-pVIII serum detected a 24 kDa protein at 12-48 h post
      infection and an additional 8 kDa protein at 24-48 h post-infection. While the 24
      kDa protein was detected in empty capsids, only the C-terminal-cleaved 8 kDa
      protein was detected in the mature virion, suggesting that amino acids147-216 of
      the conserved C-terminus of BAdV-3 pVIII are incorporated in mature virions.
      Detection of hexon protein associated with both precursor (24 kDa) and cleaved (8
      kDa) forms of pVIII suggest that the C-terminus of pVIII interacts with the
      hexon. The pVIII protein predominantly localizes to the nucleus of BAdV-3
      infected cells utilizing the classical importin alpha/beta dependent nuclear
      import pathway. Analysis of mutant pVIII demonstrated that amino acids 52-72 of
      the conserved N-terminus bind to importin alpha-3 with high affinity and are
      required for the nuclear localization. 

PMID- 24854003
TI  - A prospective evaluation of ventilator-associated conditions and infection
      related ventilator-associated conditions.
AB  - BACKGROUND: The Centers for Disease Control and Prevention has shifted policy
      away from using ventilator-associated pneumonia (VAP) and toward using ventilator
      associated conditions (VACs) as a marker of ICU quality. To date, limited
      prospective data regarding the incidence of VAC among medical and surgical ICU
      patients, the ability of VAC criteria to capture patients with VAP, and the
      potential clinical preventability of VACs are available. METHODS: This study was
      a prospective 12-month cohort study (January 2013 to December 2013). RESULTS: We
      prospectively surveyed 1,209 patients ventilated for >= 2 calendar days. Sixty
      seven VACs were identified (5.5%), of which 34 (50.7%) were classified as an
      infection-related VAC (IVAC) with corresponding rates of 7.0 and 3.6 per 1,000
      ventilator days, respectively. The mortality rate of patients having a VAC was
      significantly greater than that of patients without a VAC (65.7% vs 14.4%, P <
      .001). The most common causes of VACs included IVACs (50.7%), ARDS (16.4%),
      pulmonary edema (14.9%), and atelectasis (9.0%). Among IVACs, 44.1% were probable
      VAP and 17.6% were possible VAP. Twenty-five VACs (37.3%) were adjudicated to
      represent potentially preventable events. Eighty-six episodes of VAP occurred in
      84 patients (10.0 of 1,000 ventilator days) during the study period. The
      sensitivity of the VAC criteria for the detection of VAP was 25.9% (95% CI, 16.7%
      34.5%). CONCLUSIONS: Although relatively uncommon, VACs are associated with
      greater mortality and morbidity when they occur. Most VACs represent
      nonpreventable events, and the VAC criteria capture a minority of VAP episodes.

PMID- 24854004
TI  - Selection, language heritage, and the earnings trajectories of black immigrants
      in the United States.
AB  - Research suggests that immigrants from the English-speaking Caribbean surpass the
      earnings of U.S.-born blacks approximately one decade after arriving in the
      United States. Using data from the 1980-2000 U.S. censuses and the 2005-2007
      American Community Surveys on U.S.-born black and non-Hispanic white men as well
      as black immigrant men from all the major sending regions of the world, I
      evaluate whether selective migration and language heritage of immigrants' birth
      countries account for the documented earnings crossover. I validate the earnings
      pattern of black immigrants documented in previous studies, but I also find that
      the earnings of most arrival cohorts of immigrants from the English-speaking
      Caribbean, after residing in the United States for more than 20 years, are
      projected to converge with or slightly overtake those of U.S.-born black internal
      migrants. The findings also show three arrival cohorts of black immigrants from
      English-speaking African countries are projected to surpass the earnings of U.S.
      born black internal migrants. No arrival cohort of black immigrants is projected
      to surpass the earnings of U.S.-born non-Hispanic whites. Birth-region analysis
      shows that black immigrants from English-speaking countries experience more rapid
      earnings growth than immigrants from non-English-speaking countries. The arrival
      cohort and birth-region variation in earnings documented in this study suggest
      that selective migration and language heritage of black immigrants' birth
      countries are important determinants of their initial earnings and earnings
      trajectories in the United States. 

PMID- 24854005
TI  - Autonomous micromotor based on catalytically pneumatic behavior of balloon-like
      MnO(x)-graphene crumples.
AB  - A novel autonomous micromotor, based on catalytically pneumatic behaviour of
      balloon-like MnOx-graphene crumples, has been synthesized via an ultrasonic spray
      pyrolysis method. Through catalytic decomposition of H2O2 into O2, the gas
      accumulated in a confined space and was released to generate a strong force to
      push the micromotor. 

PMID- 24854007
TI  - Planomicrobium soli sp. nov., isolated from soil.
AB  - A Gram-staining-positive bacterium, designated strain XN13(T), was isolated from
      a soil sample collected from ALaShan National Geological Park in Inner Mongolia
      Autonomous Region, China and subjected to a taxonomic study using a polyphasic
      approach. Strain XN13(T) was found to have a range of chemical and morphological
      properties consistent with its classification in the genus Planomicrobium.
      Phylogenetic analyses based on 16S rRNA gene sequences revealed that strain
      XN13(T) was related to members of the genus Planomicrobium. The closest
      phylogenetic relatives were Planomicrobium okeanokoites NBRC 12536(T),
      Planomicrobium koreense JG07(T), Planomicrobium mcmeekinii S23F2(T) and
      Planomicrobium flavidum ISL-41(T) with 98.2%, 97.8%, 97.8% and 97.7% 16S rRNA
      gene sequence similarity, respectively. The major cellular fatty acids were
      anteiso-C(15 : 0), C(16 : 1)omega7c alcohol, iso-C(14 : 0) and C(16 : 1)omega11c.
      The predominant menaquinones were MK-8 and MK-7. The DNA G+C content was 40.3
      mol%. The DNA-DNA relatedness values between strain XN13(T) and Planomicrobium
      okeanokoites KCTC 3672(T), Planomicrobium koreense KCTC 3684(T), P. mcmeekinii
      CGMCC 1.2724(T), Planomicrobium flavidum KCTC 13261(T), Planomicrobium chinense
      CGMCC 1.3454(T) and Planomicrobium glaciei CGMCC 1.6846(T) were 36%, 30%, 34%,
      29%, 30% and 31%, respectively. The organism is different from recognized species
      of the genus Planomicrobium in several phenotypic characteristics. On the basis
      of phenotypic and genotypic properties, strain XN13(T) represents a novel species
      of the genus Planomicrobium, for which the name Planomicrobium soli sp. nov. is
      proposed. The type strain is XN13(T) ( = CGMCC 1.12259(T) = KCTC 33047(T)).

PMID- 24854006
TI  - Rhodococcus enclensis sp. nov., a novel member of the genus Rhodococcus.
AB  - A novel actinobacterial strain, designated, NIO-1009(T), was isolated from a
      marine sediment sample collected from Chorao Island, Goa, India. Phylogenetic
      analysis comparisons based on 16S rRNA gene sequences between strain NIO-1009(T)
      and other members of the genus Rhodococcus revealed that strain NIO-1009(T) had
      the closest sequence similarity to Rhodococcus kroppenstedtii DSM 44908(T) and
      Rhodococcus corynebacterioides DSM 20151(T) with 99.2 and 99.1%, respectively.
      Furthermore, DNA-DNA hybridization results showed that R. kroppenstedtii DSM
      44908(T) and R. corynebacterioides DSM 20151(T) were 39.5 (3.0%) and 41.7 (2.0%)
      with strain NIO-1009(T), respectively, which were well below the 70% limit for
      any novel species proposal. Phylogenetically strain NIO-1009(T) forms a stable
      clade with and R. kroppenstedtii DSM 44908(T) and R. corynebacterioides DSM
      20151(T) with 100% bootstrap values. Strain NIO-1009(T) contained meso
      diaminopimelic acid as the diagnostic diamino acid and galactose and arabinose as
      the cell wall sugars. The major fatty acids were C(16 : 0), C(18 : 1)omega9c,
      C(16 : 1)(omega6c and/or omega7c) and 10-methyl C(18 : 0). The only menaquinone
      detected was MK-8(H2), while the major polar lipids were diphosphatidylglycerol,
      phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol,
      phosphatidylinositol mannoside and one unknown phospholipid. The G+C content of
      the genomic DNA was 66.9 mol%. The phenotypic and genotypic data showed that
      strain NIO-1009(T) warrants recognition as a novel species of the genus
      Rhodococcus for which the name Rhodococcus enclensis sp. nov., is proposed; the
      type strain is NIO-1009(T) ( = NCIM 5452(T) = DSM 45688(T)).

PMID- 24854008
TI  - Fulvimarina manganoxydans sp. nov., isolated from a deep-sea hydrothermal plume
      in the south-west Indian Ocean.
AB  - An aerobic, Mn(II)-oxidizing, Gram-negative bacterium, strain 8047(T), was
      isolated from a deep-sea hydrothermal vent plume in the south-west Indian Ocean.
      The strain was rod-shaped and motile with a terminal flagellum, and formed
      yellowish colonies. It produced catalase and oxidase, hydrolysed gelatin and
      reduced nitrate. 16S rRNA gene sequence analysis showed that strain 8047(T)
      belonged to the order Rhizobiales of the class Alphaproteobacteria, and was
      phylogenetically most closely related to the genus Fulvimarina, sharing 94.4%
      sequence identity with the type strain of the type species. The taxonomic
      affiliation of strain 8047(T) was supported by phylogenetic analysis of four
      additional housekeeping genes, gyrB, recA, rpoC and rpoB. The predominant
      respiratory lipoquinone of strain 8047(T) was Q-10, the major fatty acid was C(18
      : 1)omega7c and the DNA G+C content was 61.7 mol%. On the basis of the phenotypic
      and genotypic characteristics determined in this study, strain 8047(T) represents
      a novel species within the genus Fulvimarina, for which the name Fulvimarina
      manganoxydans sp. nov. is proposed. The type strain is strain 8047(T) ( =
      CGMCC1.10972(T) = JCM 18890(T)).

PMID- 24854009
TI  - Protonation and deprotonation enthalpies of alloxan and implications for the
      structure and energy of its complexes with water: a computational study.
AB  - The optimized geometries, harmonic vibrational frequencies, and energies of the
      structures of monohydrated alloxan were computed at the DFT/omegaB97X-D and
      B3LYP/6-311++G** level of theory. Results confirm that the monohydrate exists as
      a dipolar alloxan-water complex which represents a global minimum on the
      potential energy surface (PES). Trajectory dynamics simulations show that attempt
      to reorient this monohydrate, to a more favorable orientation for H-bonding, is
      opposed by an energy barrier of 25.07 kJ/mol. Alloxan seems to prefer acting as
      proton donor than proton acceptor. A marked stabilization due to the formation of
      N-H-OH2 bond is observed. The concerted proton donor-acceptor interaction of
      alloxan with one H2O molecule does not increase the stability of the alloxan
      water complex. The proton affinity of the O and N atoms and the deprotonation
      enthalpy of the NH bond of alloxan are computed at the same level of theory.
      Results are compared with recent data on uracil, thymine, and cytosine. The
      intrinsic acidities and basicities of the four pyrimidines were discussed.
      Results of the present study reveal that alloxan is capable of forming stronger H
      bonds and more stable cyclic complex with water; yet it is of much lower basicity
      than other pyrimidines. 

PMID- 24854010
TI  - Intraperitoneal interleukin-6 levels predict peritoneal solute transport rate: a
      prospective cohort study.
AB  - BACKGROUND: To evaluate the association of dialysate interleukin-6 (IL-6), a
      marker of ongoing peritoneal inflammation, with the alteration of peritoneal
      solute transport rate (PSTR) in continuous ambulatory peritoneal dialysis (CAPD)
      patients. METHODS: Stable CAPD patients were enrolled in the present study. A
      total of 128 patients were analyzed in this prospective study. IL-6 concentration
      in the overnight effluent was determined and expressed as the IL-6 appearance
      rate (IL-6AR). Mass transfer area coefficients of creatinine (MTACcr) were
      measured at enrollment and 12 months later. Logistic regression was used to
      examine the association between IL-6AR and change in MTACcr. RESULTS:
      Multivariable linear regression showed that historical glucose exposure was
      significantly associated with dialysate IL-6AR level [beta = 0.008 (0.001-0.015),
      p = 0.021]. After 12 months, MTACcr was significantly increased [6.40 (4.70-8.75)
      vs. 7.14 (5.69-8.73) ml/min, p = 0.004], while ultrafiltration capacity decreased
      [4 h UF 340 (220-400) vs. 280 (180-380) ml, p = 0.006]. Compared to the patients
      with stable PSTR, the dialysate IL-6AR in patients with increasing PSTR was
      significantly higher [277.08 (247.45-349.53) vs. 263.18 (69.94-286.72) pg/min, p
      = 0.015]. Patients with increasing PSTR had lower residual renal function [0.79
      (0-2.12) vs. 1.70 (0.39-3.38) ml/min, p = 0.006] and less urine output [225 (0
      600) vs. 500 (125-900) ml/24 h, p = 0.014]. Logistic analysis showed that both
      high dialysate IL-6AR [OR 1.333 and 95% CI (1.024-1.735), p = 0.033] and low RRF
      [OR 0.831 and 95% CI (0.699-0.988), p = 0.036] were independent risk factors for
      increasing PSTR. CONCLUSIONS: This prospective study suggests that
      intraperitoneal IL-6 is a predictor of increasing PSTR in peritoneal dialysis
      patients.

PMID- 24854011
TI  - Idiopathic intracranial hypertension in childhood: pitfalls in diagnosis.
AB  - AIM: Idiopathic intracranial hypertension (IIH) is prone to misdiagnosis. Our aim
      was to identify the reasons for this in children in our region referred for
      suspected IIH. METHOD: We reviewed the records of all children referred with
      symptoms and/or signs consistent with raised intracranial pressure (ICP) and
      normal magnetic resonance imaging of the brain to our tertiary neurology unit
      over 4 years. IIH was confirmed after expert ophthalmology including
      ultrasound/tomography and advanced cerebrospinal fluid (CSF) pressure studies.
      RESULTS: Of 15 children (six males, nine females; median age 12y, range 3-15y),
      six (five females, one male) were confirmed to have IIH. All weighed above the
      91st centile and were over 10 years old. Four of the six had raised ICP secondary
      to other causes. Four had been misdiagnosed locally with papilloedema, three had
      drusen, and one had 'crowded discs'. Two had raised CSF pressures on standard
      lumbar puncture, but 20-minute steady state and infusion studies were normal,
      with symptoms settling after therapy was withdrawn. INTERPRETATION: Misdiagnosis
      of IIH was frequent, but could be reduced by (1) expert ophthalmological
      fundoscopy, orbital ultrasound, and optical coherence tomography; (2) expert
      neuroradiology; and (3) assessment of steady state CSF pressure rather than
      standard opening pressure in centimetres of water.

PMID- 24854013
TI  - The making of a great surgeon.

PMID- 24854016
TI  - Cold storage to overcome dormancy affects the carbohydrate status and
      photosynthetic capacity of Rhododendron simsii.
AB  - Global warming leads to increasing irregular and unexpected warm spells during
      autumn, and therefore natural chilling requirements to break dormancy are at
      risk. Controlled cold treatment can provide an answer to this problem.
      Nevertheless, artificial cold treatment will have consequences for carbon
      reserves and photosynthesis. In this paper, the effect of dark cold storage at 7 
      degrees C to break flower bud dormancy in the evergreen Rhododendron simsii was
      quantified. Carbohydrate and starch content in leaves and flower buds of an early
      ('Nordlicht'), semi-early ('M. Marie') and late ('Mw. G. Kint') flowering
      cultivar showed that carbon loss due to respiration was lowest in 'M. Marie',
      while 'Mw. G. Kint' was completely depleted of starch reserves at the end of cold
      treatment. Gene isolation resulted in a candidate gene for sucrose synthase (SUS)
      RsSus, which appears to be homologous to AtSus3 and had a clear increase in
      expression in leaves during cold treatment. Photosynthesis measurements on
      'Nordlicht' and the late-flowering cultivar 'Thesla' showed that during cold
      treatment, dark respiration decreased 58% and 63%, respectively. Immediately
      after cold treatment, dark respiration increased and stabilised after 3 days. The
      light compensation point followed the same trend as dark respiration. Quantum
      efficiency showed no significant changes during the first days after cold
      treatment, but was significantly higher than in plants with dormant flower buds
      at the start of cold treatment. In conclusion, photosynthesis stabilised 3 days
      after cold treatment and was improved compared to the level before cold
      treatment. 

PMID- 24854015
TI  - High-resolution modeling of transmembrane helical protein structures from distant
      homologues.
AB  - Eukaryotic transmembrane helical (TMH) proteins perform a wide diversity of
      critical cellular functions, but remain structurally largely uncharacterized and
      their high-resolution structure prediction is currently hindered by the lack of
      close structural homologues. To address this problem, we present a novel and
      generic method for accurately modeling large TMH protein structures from distant
      homologues exhibiting distinct loop and TMH conformations. Models of the
      adenosine A2AR and chemokine CXCR4 receptors were first ranked in GPCR-DOCK blind
      prediction contests in the receptor structure accuracy category. In a benchmark
      of 50 TMH protein homolog pairs of diverse topology (from 5 to 12 TMHs), size
      (from 183 to 420 residues) and sequence identity (from 15% to 70%), the method
      improves most starting templates, and achieves near-atomic accuracy prediction of
      membrane-embedded regions. Unlike starting templates, the models are of suitable
      quality for computer-based protein engineering: redesigned models and redesigned
      X-ray structures exhibit very similar native interactions. The method should
      prove useful for the atom-level modeling and design of a large fraction of
      structurally uncharacterized TMH proteins from a wide range of structural
      homologues. 

PMID- 24854014
TI  - Structural Basis for the Ubiquitin-Linkage Specificity and deISGylating activity
      of SARS-CoV papain-like protease.
AB  - Severe acute respiratory syndrome coronavirus (SARS-CoV) encodes a papain-like
      protease (PLpro) with both deubiquitinating (DUB) and deISGylating activities
      that are proposed to counteract the post-translational modification of signaling
      molecules that activate the innate immune response. Here we examine the
      structural basis for PLpro's ubiquitin chain and interferon stimulated gene 15
      (ISG15) specificity. We present the X-ray crystal structure of PLpro in complex
      with ubiquitin-aldehyde and model the interaction of PLpro with other ubiquitin
      chain and ISG15 substrates. We show that PLpro greatly prefers K48- to K63-linked
      ubiquitin chains, and ISG15-based substrates to those that are mono
      ubiquitinated. We propose that PLpro's higher affinity for K48-linked ubiquitin
      chains and ISG15 stems from a bivalent mechanism of binding, where two ubiquitin
      like domains prefer to bind in the palm domain of PLpro with the most distal
      ubiquitin domain interacting with a "ridge" region of the thumb domain.
      Mutagenesis of residues within this ridge region revealed that these mutants
      retain viral protease activity and the ability to catalyze hydrolysis of mono
      ubiquitin. However, a select number of these mutants have a significantly reduced
      ability to hydrolyze the substrate ISG15-AMC, or be inhibited by K48-linked
      diubuiquitin. For these latter residues, we found that PLpro antagonism of the
      nuclear factor kappa-light-chain-enhancer of activated B-cells (NFkappaB)
      signaling pathway is abrogated. This identification of key and unique sites in
      PLpro required for recognition and processing of diubiquitin and ISG15 versus
      mono-ubiquitin and protease activity provides new insight into ubiquitin-chain
      and ISG15 recognition and highlights a role for PLpro DUB and deISGylase activity
      in antagonism of the innate immune response. 

PMID- 24854019
TI  - Investigating groundwater-lake interactions by hydraulic heads and a water
      balance.
AB  - Discharge of groundwater into lakes (lacustrine groundwater discharge, LGD) can
      play a major role in water balances of lakes. Unfortunately, studies often
      neglect this input path because of methodological difficulties in its
      determination. Direct measurements of LGD are labor-consuming and prone to error.
      The present study uses both spatially variable hydraulic-head data and
      meteorological data to estimate groundwater input by LGD and lake water output
      through infiltration. The study sites are two shallow, groundwater-fed lakes
      without any surface inflows or outflows. Horizontally interpolated groundwater
      heads were combined with lake water levels to obtain vertical hydraulic gradients
      between the aquifer and the lake, which are separated by a thick layer of lake
      bed sediment which has a much lower hydraulic conductivity than the underlying
      aquifer. By fitting the hydraulic gradient to the results of a simple mass
      balance and considering the process of clogging, we were able to estimate the
      hydraulic conductivity of the lake bed sediments. We calculated groundwater
      inputs by LGD and lake water outputs by infiltration on an annual basis. Although
      our method requires several assumptions, the results are reasonable and provide
      useful information about the exchange between the aquifer and the lake, which
      can, for example, be used for the calculation of nutrient mass balances. 

PMID- 24854017
TI  - The overlap of neural selectivity between faces and words: evidences from the
      N170 adaptation effect.
AB  - Faces and words both evoke an N170, a strong electrophysiological response that
      is often used as a marker for the early stages of expert pattern perception. We
      examine the relationship of neural selectivity between faces and words by using a
      novel application of cross-category adaptation to the N170. We report a strong
      asymmetry between N170 adaptation induced by faces and by words. This is the
      first electrophysiological result showing that neural selectivity to faces
      encompasses neural selectivity to words and suggests that the N170 response to
      faces constitutes a neural marker for versatile representations of familiar
      visual patterns. 

PMID- 24854018
TI  - Online and post-trial feedback differentially affect implicit adaptation to a
      visuomotor rotation.
AB  - Multiple motor learning processes can be discriminated in visuomotor rotation
      paradigms. At least four processes have been proposed: Implicit adaptation
      updates an internal model based on prediction errors. Model-free reinforcement
      reinforces actions that achieve task success. Use-dependent learning favors
      repetition of prior movements, and strategic learning uses explicit knowledge
      about the task. The current experiment tested whether the processes involved in
      motor learning differ when visual feedback is altered. Specifically, we
      hypothesized that online and post-trial feedback would cause different amounts of
      implicit adaptation. Twenty subjects performed drawing movements to targets under
      a 45 degrees  counterclockwise visuomotor rotation while aiming at a clockwise
      adjacent target. Subjects received visual feedback via a cursor on a screen. One
      group saw the cursor throughout the movement (online feedback), while the other
      only saw the final position after movement execution (post-trial feedback). Both
      groups initially hit the target by applying the strategy. After 80 trials,
      subjects with online feedback had drifted in clockwise direction [mean direction
      error: 15.1 degrees  (SD 11.2 degrees )], thus overcompensating the rotation.
      Subjects with post-trial feedback remained accurate [mean: 0.7 degrees  (SD 2.0
      degrees ), TIME * GROUP: F = 3.926, p = 0.003]. We interpret this
      overcompensation to reflect implicit adaptation isolated from other mechanisms,
      because it is driven by prediction error rather than task success (model-free
      reinforcement) or repetition (use-dependent learning). The current findings
      extend previous work (e.g., Mazzoni and Krakauer in J Neurosci 26:3642-3645,
      2006; Hinder et al. in Exp Brain Res 201:191-207, 2010) and suggest that online
      feedback promotes more implicit adaptation than does post-trial feedback.

PMID- 24854020
TI  - Increased beta 2 defensin in recurrent aphthous ulcer.
AB  - OBJECTIVES: It was hypothesized that beta 2 defensin (BD-2) is increased in RAU
      lesions compared with healthy controls to promote anti-microbial host defence.
      METHODS: RAU and control mucosa samples were subjected to quantitative real-time
      PCR and immunostained for BD-2, CD68, mast cell tryptase and 4-hydroxynonenal
      (4HNE). The effect of tumour necrosis factor-alpha (TNF-alpha) +/- interleukin
      17C (IL-17C), without and with vitamin K3, was studied on BD-2 expression in
      epithelial SCC-25 cells. RESULTS: Although BD-2 mRNA did not differ between
      healthy and RAU mucosa, BD-2 stained strongly in acute-phase RAU epithelium (P =
      0.001). In controls, subepithelial BD-2(+) cells were mast cells and macrophages,
      whereas in RAU, most infiltrating leucocytes were BD-2(+) (P = 0.004). In cell
      culture, BD-2 was increased 124-fold by TNF-alpha (P < 0.0001) and 208-fold
      synergistically together with IL-17C (P < 0.0001). 4HNE staining of RAU
      epithelium was not significantly increased, and vitamin K3-induced reactive
      oxygen species (ROS) did not affect BD-2. CONCLUSIONS: Anti-microbial BD-2 was
      not affected by oxidative stress but was highly increased in the epithelial and
      immigrant cells in the acute-phase RAU lesions, probably in part synergistically
      by TNF-alpha and epithelial IL-17C, which are known to be induced by activation
      of danger-signal receptors by pathogen- and/or damage-associated molecular
      patterns.

PMID- 24854021
TI  - The evolving field of gut rehabilitation.

PMID- 24854024
TI  - Notes from the field: a cluster of lymphocytic choriomeningitis virus infections
      transmitted through organ transplantation-Iowa, 2013.

PMID- 24854023
TI  - Introduction of the lung allocation score in Germany.
AB  - The aim of this study was to assess performance of the new lung allocation system
      in Germany based on lung allocation score (LAS). Retrospective analysis of
      waitlist (WL) outflow, lung transplantation (LTx) activity and 3-month outcomes
      comparing 1-year pre- and post-LAS introduction on December 10, 2011 was
      performed. Following LAS introduction, WL registrations remained constant, while
      WL mortality fell by 23% (p = 0.04). Reductions in WL mortality occurred in
      patients with cystic fibrosis (CF; -52%), emphysema (chronic obstructive
      pulmonary disease [COPD]; -49%) and pulmonary hypertension (PH; -67%), but not
      idiopathic pulmonary fibrosis (IPF; +48%). LTx activity increased by 9% (p =
      0.146). Compared to pre-LAS, more patients with IPF (32% vs. 29%) and CF (20% vs.
      18%) underwent transplantation and comparatively fewer with COPD (30% vs. 39%).
      Median LAS among transplant recipients was highest in PH (53) and IPF (49) and
      lowest in COPD (34). Transplantation under invasive respiratory support increased
      to 13% (in CF 28%, +85%, p = 0.017). Three-month survival remained unchanged
      (pre: 96.1% and post: 94.9%, p = 0.94). Following LAS implementation in Germany,
      reductions in waiting list size and WL mortality were observed. Composition of
      transplant recipients changed, with fewer COPD and more IPF recipients.
      Transplantation under invasive respiratory support increased. Reductions in WL
      mortality were most pronounced among CF and PH patients.

PMID- 24854025
TI  - Hemorrhagic shock one month following uncomplicated liver transplantation.

PMID- 24854027
TI  - Implications of inadequate lymph node staging in resectable gastric cancer: a
      contemporary analysis using the National Cancer Data Base.
AB  - BACKGROUND: National guidelines recommend examination of >= 15 lymph nodes for
      adequate staging of resectable gastric adenocarcinoma (GA). The relevance of
      these guidelines, which were established before the increasing use of
      multimodality therapy, and the impact of inadequate lymph node staging (LNS) in a
      contemporary cohort have not been extensively explored. METHODS: Stage I-III GA
      patients who underwent gastrectomy from 1998 to 2011 were identified using the
      National Cancer Data Base. Trends in LNS adequacy, predictors of inadequate LNS
      (< 15 LN examined) and the relationship between LNS and overall survival (OS)
      were analyzed. RESULTS: In 22,409 patients, compliance with LNS guidelines was
      poor (inadequate LNS in 61.2% of cases, median LN harvested in 11.0%).
      Subtotal/partial gastrectomy was the strongest predictor of inadequate LNS (OR =
      2.01, P < .001). Survival analyses included 9139 patients with minimum 5 years
      follow-up; median, 1-year, and 5-year survival was 35.6 months, 75.5%, and 39.7%,
      respectively. LN positivity (HR = 1.90) and age > 76 years (HR = 1.73) were the
      strongest predictors of worse OS (both P < .001). Inadequate LNS was
      independently associated with worse OS (HR = 1.33, P < .001). Median OS after
      inadequate compared to adequate LNS was significantly worse (33.3 months versus
      42.0 months, P < .001), regardless of AJCC clinical stage subgroup or tumor T
      classification (both P < .001). CONCLUSIONS: Adequate LNS is achieved in a
      minority of patients. Inadequate LNS was independently associated with worse OS.
      Examination of >= 15 LN is a reproducible prognosticator of gastric cancer
      outcomes in the United States and should continue to serve as a benchmark for
      quality of care.

PMID- 24854028
TI  - Performance in the FRCR (UK) Part 2B examination: analysis of factors associated
      with success.
AB  - AIM: To assess factors that influence pass rates and examination scores in the
      Fellowship of the Royal College of Radiologists (FRCR) 2B examination. MATERIALS
      AND METHODS: 2238 attempts at the FRCR 2B examination were evaluated between
      Spring 2006 and Spring 2010. Pass rates and examination scores were analysed by
      gender and ethnicity, and the influence of factors such as radiology training (UK
      versus non-UK), sitting (Spring versus Autumn), and the presence of an
      undergraduate or postgraduate degree were examined. RESULTS: 1571 candidates made
      2238 examination attempts, with an overall pass rate of 59.4% (63.1% at first
      attempt). 66.2% entrants were male; 48.8% attempts were by candidates from a UK
      radiology training scheme. UK candidates were significantly more likely to pass
      than non-UK candidates (p < 0.0001). White candidates were more likely to pass at
      first or second attempt than non-white candidates (p < 0.0001), but when
      restricted to UK entrants ethnicity did not influence success at first attempt.
      Overall, females were more successful than males (p < 0.001). Presence of an
      undergraduate (p = 0.19) or postgraduate (p = 0.80) degree did not affect pass
      rate at first attempt for UK candidates. However, logistic regression
      demonstrated that the only significant factor influencing pass rates at first
      attempt was whether radiology training was undertaken in the UK (p < 0.0001). A
      trend towards increased pass rates in autumn sittings was seen (p = 0.06), but
      ethnicity (p = 0.99) and gender (p = 0.41) were not significant factors.
      CONCLUSION: The FRCR 2B examination is non-discriminatory for UK candidates with
      respect to gender and ethnicity. Poorer performance of non-UK trained candidates
      is a consistent outcome in the literature.

PMID- 24854026
TI  - Chronic stress suppresses the expression of cutaneous hypothalamic-pituitary
      adrenocortical axis elements and melanogenesis.
AB  - Chronic stress can affect skin function, and some skin diseases might be
      triggered or aggravated by stress. Stress can activate the central hypothalamic
      pituitary-adrenocortical (HPA) axis, which causes glucocorticoid levels to
      increase. The skin has HPA axis elements that react to environmental stressors to
      regulate skin functions, such as melanogenesis. This study explores the mechanism
      whereby chronic stress affects skin pigmentation, focusing on the HPA axis, and
      investigates the role of glucocorticoids in this pathway. We exposed C57BL/6 male
      mice to two types of chronic stress, chronic restraint stress (CRS) and chronic
      unpredictable mild stress (CUMS). Mice subjected to either stress condition
      showed reduced melanogenesis. Interestingly, CRS and CUMS triggered reductions in
      the mRNA expression levels of key factors involved in the HPA axis in the skin.
      In mice administered corticosterone, decreased melanin synthesis and reduced
      expression of HPA axis elements were observed. The reduced expression of HPA axis
      elements and melanogenesis in the skin of stressed mice were reversed by RU486 (a
      glucocorticoid receptor antagonist) treatment. Glucocorticoids had no significant
      inhibitory effect on melanogenesis in vitro. These results suggest that, high
      levels of serum corticosterone induced by chronic stress can reduce the
      expression of elements of the skin HPA axis by glucocorticoid-dependent negative
      feedback. These activities can eventually result in decreased skin pigmentation.
      Our findings raise the possibility that chronic stress could be a risk factor for
      depigmentation by disrupting the cutaneous HPA axis and should prompt
      dermatologists to exercise more caution when using glucocorticoids for treatment.

PMID- 24854029
TI  - Dual-source CT versus single-source 64-section CT angiography for coronary artery
      disease: A meta-analysis.
AB  - AIM: To perform a meta-analysis to compare the diagnostic performance of single
      source 64-section computed tomography (CT) versus dual-source CT angiography for
      diagnosis of coronary artery disease (CAD). MATERIALS AND METHODS: The Cochrane
      Library, MEDLINE, and EMBASE were searched for relevant original papers.
      Inclusion criteria were (1) significant CAD defined as >=50% reduction in luminal
      diameter by invasive coronary angiography as reference standard; (2) single
      source 64-section CT or dual-source CT was used; (3) results were reported in
      absolute numbers of true-positive, false-positive, true-negative, and false
      negative results or sufficiently detailed data for deriving these numbers were
      presented. A random-effects model was used for the meta-analysis. RESULTS: Fifty
      one papers including 3966 patients who underwent single-source 64-section CT and
      2047 patients who underwent dual-source CT at a per-patient level were pooled.
      The diagnostic values of single-source 64-section CT versus dual-source CT were
      97% versus 97% for sensitivity (p = 0.386), 78% versus 86% for specificity (p <
      0.001), 90% versus 85% for positive predictive value (PPV; p < 0.001), 93% versus
      97% for negative predictive value (NPV; p = 0.001), 6.8 versus 6.5 for positive
      likelihood ratio (p = 0.018), 0.04 versus 0.04 for negative likelihood ratio (p =
      0.625), and 191.59 versus 207.37 for diagnostic odds ratio (p = 0.043),
      respectively. CONCLUSION: Dual-source CT and single-source 64-section CT have
      similar negative likelihood ratios and, therefore, there was no significant
      difference in their utility to rule out CAD in intermediate-risk patients.
      However, compared to single-source 64-section CT, dual-source CT has
      significantly higher specificity, so that CT-based decisions for subsequent
      coronary catheter angiography are more accurate.

PMID- 24854030
TI  - Rising tides or rising stars?: Dynamics of shared attention on Twitter during
      media events.
AB  - "Media events" generate conditions of shared attention as many users
      simultaneously tune in with the dual screens of broadcast and social media to
      view and participate. We examine how collective patterns of user behavior under
      conditions of shared attention are distinct from other "bursts" of activity like
      breaking news events. Using 290 million tweets from a panel of 193,532
      politically active Twitter users, we compare features of their behavior during
      eight major events during the 2012 U.S. presidential election to examine how
      patterns of social media use change during these media events compared to
      "typical" time and whether these changes are attributable to shifts in the
      behavior of the population as a whole or shifts from particular segments such as
      elites. Compared to baseline time periods, our findings reveal that media events
      not only generate large volumes of tweets, but they are also associated with (1)
      substantial declines in interpersonal communication, (2) more highly concentrated
      attention by replying to and retweeting particular users, and (3) elite users
      predominantly benefiting from this attention. These findings empirically
      demonstrate how bursts of activity on Twitter during media events significantly
      alter underlying social processes of interpersonal communication and social
      interaction. Because the behavior of large populations within socio-technical
      systems can change so dramatically, our findings suggest the need for further
      research about how social media responses to media events can be used to support
      collective sensemaking, to promote informed deliberation, and to remain resilient
      in the face of misinformation. 

PMID- 24854031
TI  - Chemical and genetic discrimination of Cistanches Herba based on UPLC-QTOF/MS and
      DNA barcoding.
AB  - Cistanches Herba (Rou Cong Rong), known as "Ginseng of the desert", has a
      striking curative effect on strength and nourishment, especially in kidney
      reinforcement to strengthen yang. However, the two plant origins of Cistanches
      Herba, Cistanche deserticola and Cistanche tubulosa, vary in terms of
      pharmacological action and chemical components. To discriminate the plant origin
      of Cistanches Herba, a combined method system of chemical and genetic--UPLC
      QTOF/MS technology and DNA barcoding--were firstly employed in this study. The
      results indicated that three potential marker compounds (isomer of campneoside
      II, cistanoside C, and cistanoside A) were obtained to discriminate the two
      origins by PCA and OPLS-DA analyses. DNA barcoding enabled to differentiate two
      origins accurately. NJ tree showed that two origins clustered into two clades.
      Our findings demonstrate that the two origins of Cistanches Herba possess
      different chemical compositions and genetic variation. This is the first reported
      evaluation of two origins of Cistanches Herba, and the finding will facilitate
      quality control and its clinical application.

PMID- 24854032
TI  - Can we predict which hospitalised patients are in their last year of life? A
      prospective cross-sectional study of the Gold Standards Framework Prognostic
      Indicator Guidance as a screening tool in the acute hospital setting.
AB  - BACKGROUND: Screening to identify hospital inpatients with a short life
      expectancy may be a way to improve care towards the end of life. The Gold
      Standards Framework Prognostic Indicator Guidance is a screening tool that has
      recently been advocated for use in the hospital setting. AIM: To assess the
      clinical utility of the Gold Standards Framework Prognostic Indicator Guidance as
      a screening tool in an acute hospital setting. MAIN OUTCOME MEASURES: Mortality
      at 6 and 12 months and sensitivity, specificity and predictive value of the Gold
      Standards Framework Prognostic Indicator Guidance at 1 year. DESIGN, SETTING AND
      PARTICIPANTS: Prospective cross-sectional study of 501 adult inpatients in a
      tertiary New Zealand teaching hospital screened utilising the Gold Standards
      Framework Prognostic Indicator Guidance. RESULTS: A total of 99 patients were
      identified as meeting at least one of the Gold Standards Framework Prognostic
      Indicator Guidance triggers. In this group, 6-month mortality was 56.6% and 12
      month mortality was 67.7% compared with 5.2% and 10%, respectively, for those not
      identified as meeting the criteria. The sensitivity and specificity of the Gold
      Standards Framework Prognostic Indicator Guidance at 1 year were 62.6% and 91.9%,
      respectively, with a positive predictive value of 67.7% and a negative predictive
      value of 90.0%. CONCLUSION: The sensitivity, specificity and predictive values of
      the Gold Standards Framework Prognostic Indicator Guidance in this study are
      comparable to, or better than, results of studies identifying patients with a
      limited life expectancy in particular disease states (e.g. heart failure and
      renal failure). Screening utilising the Gold Standards Framework Prognostic
      Indicator Guidance in the acute setting could be the first step towards
      implementing a more systematic way of addressing patient need--both current
      unrecognised and future anticipated--thereby improving outcomes for this
      population.

PMID- 24854033
TI  - Formal and informal support of family caregivers managing medications for
      patients who receive end-of-life care at home: a cross-sectional survey of
      caregivers.
AB  - BACKGROUND: Managing medications is a complex responsibility of family caregivers
      caring for end-of-life patients. This study characterizes caregivers with and
      without formal/informal support managing medications for patients who receive end
      of-life care at home. AIM: To explore factors related to caregivers' support with
      managing medications for end-of-life home hospice patients. DESIGN: A convenience
      sampled, cross-sectional telephone survey. SETTING/PARTICIPANTS: Computer
      assisted telephone interviews were administered to 120 caregivers managing
      medications, who were referred by five Chicago-based home hospice services. We
      measured caregivers' additional formal (paid) and informal (unpaid) support with
      managing medications, and caregiver/patient socio-demographic, relational, and
      health characteristics. RESULTS: While 47 (39%) had no additional support with
      managing medications, 27 (22.5%) had formal support, 37 (31%) informal, and 9
      (7.5%) both. Seven caregivers (19%) with formal and 13 (31%) with informal
      support reported disagreements concerning treatment plans. Caregivers lacking
      formal support tended to be racial/ethnic minorities, live with the patient in
      their home, or report greater emotional burden. Caregivers with formal support
      tended to report higher education/income, lower mutuality, or care for a patient
      with over 6 months' hospice enrollment. Caregivers lacking informal support
      tended to be spousal caregivers, live with the patient, or have experience caring
      for another dying person. CONCLUSION: Our study suggests that high proportions of
      caregivers may not have support managing medications for patients receiving
      hospice care at home. More research should examine whether the observed
      variations in obtaining support indicate disparities or unmet needs among
      caregivers. Disagreement about treatment with formal/informal support also
      warrants further investigation.

PMID- 24854034
TI  - Scabies mite inactive serine proteases are potent inhibitors of the human
      complement lectin pathway.
AB  - Scabies is an infectious skin disease caused by the mite Sarcoptes scabiei and
      has been classified as one of the six most prevalent epidermal parasitic skin
      diseases infecting populations living in poverty by the World Health
      Organisation. The role of the complement system, a pivotal component of human
      innate immunity, as an important defence against invading pathogens has been well
      documented and many parasites have an arsenal of anti-complement defences. We
      previously reported on a family of scabies mite proteolytically inactive serine
      protease paralogues (SMIPP-Ss) thought to be implicated in host defence evasion.
      We have since shown that two family members, SMIPP-S D1 and I1 have the ability
      to bind the human complement components C1q, mannose binding lectin (MBL) and
      properdin and are capable of inhibiting all three human complement pathways. This
      investigation focused on inhibition of the lectin pathway of complement
      activation as it is likely to be the primary pathway affecting scabies mites.
      Activation of the lectin pathway relies on the activation of MBL, and as SMIPP-S
      D1 and I1 have previously been shown to bind MBL, the nature of this interaction
      was examined using binding and mutagenesis studies. SMIPP-S D1 bound MBL in
      complex with MBL-associated serine proteases (MASPs) and released the MASP-2
      enzyme from the complex. SMIPP-S I1 was also able to bind MBL in complex with
      MASPs, but MASP-1 and MASP-2 remained in the complex. Despite these differences
      in mechanism, both molecules inhibited activation of complement components
      downstream of MBL. Mutagenesis studies revealed that both SMIPP-Ss used an
      alternative site of the molecule from the residual active site region to inhibit
      the lectin pathway. We propose that SMIPP-Ss are potent lectin pathway inhibitors
      and that this mechanism represents an important tool in the immune evasion
      repertoire of the parasitic mite and a potential target for therapeutics. 

PMID- 24854040
TI  - Blind Snipers: Relevant Off Target Effects of Non-chemotherapeutic Agents in
      Oncology: Review of the Literature.
AB  - In recent years an increasing attention is focused on the potential effects of
      drugs on cancer incidence and/or cancer survival. Many medications of common use,
      developed for a variety of medical non-cancer situations, have been found to have
      potential anti- cancer effects. In this article, we performed an overview of the
      literature evidence for several commonly used non-cancer medications, such as
      aspirin, beta-blockers, metformin and other anti- diabetics, cardiac glycosides,
      anticoagulant heparin, statins, psychotropic drugs, vitamins, calcium and
      estrogens which have been shown to have anticancer effects, in observational and
      experimental studies. A huge amount of data supports the idea that a few of these
      commonly used medicines could decrease cancer death-rate, particularly aspirin,
      statins and metformin, crosswise different types of cancer. To date, no mature
      data are available from randomized and prospective trials; perhaps, the results
      of some studies underway will allow us to answer some questions on the possible
      use of these drugs in our clinical practice in primary and secondary prevention,
      or even in adjuvant setting. 

PMID- 24854039
TI  - Role of ferulic acid in the amelioration of ionizing radiation induced
      inflammation: a murine model.
AB  - Ionizing radiation is responsible for oxidative stress by generating reactive
      oxygen species (ROS), which alters the cellular redox potential. This change
      activates several redox sensitive enzymes which are crucial in activating
      signaling pathways at molecular level and can lead to oxidative stress induced
      inflammation. Therefore, the present study was intended to assess the anti
      inflammatory role of ferulic acid (FA), a plant flavonoid, against radiation
      induced oxidative stress with a novel mechanistic viewpoint. FA was administered
      (50 mg/kg body wt) to Swiss albino mice for five consecutive days prior to
      exposing them to a single dose of 10 Gy 60Co gamma-irradiation. The dose of FA
      was optimized from the survival experiment and 50 mg/kg body wt dose showed
      optimum effect. FA significantly ameliorated the radiation induced inflammatory
      response such as phosphorylation of IKKalpha/beta and IkappaBalpha and consequent
      nuclear translocation of nuclear factor kappa B (NF-kappaB). FA also prevented
      the increase of cycloxygenase-2 (Cox-2) protein, inducible nitric oxide synthase
      2 (iNOS-2) gene expression, lipid peroxidation in liver and the increase of tumor
      necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in serum. It was
      observed that exposure to radiation results in decreased activity of superoxide
      dismutase (SOD), catalase (CAT) and the pool of reduced glutathione (GSH)
      content. However, FA treatment prior to irradiation increased the activities of
      the same endogenous antioxidants. Thus, pretreatment with FA offers protection
      against gamma radiation induced inflammation. 

PMID- 24854042
TI  - Only your eyes tell me what you like: Exploring the liking effect induced by
      other's gaze.
AB  - Our preferences are sensitive to social influences. For instance, we like more
      the objects that are looked-at by others than non-looked-at objects. Here, we
      explored this liking effect, using a modified paradigm of attention cueing by
      gaze. First, we investigated if the liking effect induced by gaze relied on
      motoric representations of the target object by testing if the liking effect
      could be observed for non-manipulable (alphanumeric characters) as well as for
      manipulable items (common tools). We found a significant liking effect for the
      alphanumeric items. Second, we tested if another type of powerful social cue
      could also induce a liking effect. We used an equivalent paradigm but with
      pointing hands instead of gaze cues. Pointing hands elicited a robust attention
      orienting effect, but they did not induce any significant liking effect. This
      study extends previous findings and reinforces the view of eye gaze as a special
      cue in human interactions. 

PMID- 24854041
TI  - Recovery of hypoglycemia awareness in long-standing type 1 diabetes: a
      multicenter 2 * 2 factorial randomized controlled trial comparing insulin pump
      with multiple daily injections and continuous with conventional glucose self
      monitoring (HypoCOMPaSS).
AB  - OBJECTIVE: To determine whether impaired awareness of hypoglycemia (IAH) can be
      improved and severe hypoglycemia (SH) prevented in type 1 diabetes, we compared
      an insulin pump (continuous subcutaneous insulin infusion [CSII]) with multiple
      daily injections (MDIs) and adjuvant real-time continuous glucose monitoring (RT)
      with conventional self-monitoring of blood glucose (SMBG). RESEARCH DESIGN AND
      METHODS: A 24-week 2 * 2 factorial randomized controlled trial in adults with
      type 1 diabetes and IAH was conducted. All received comparable education,
      support, and congruent therapeutic targets aimed at rigorous avoidance of
      biochemical hypoglycemia without relaxing overall control. Primary end point was
      between-intervention difference in 24-week hypoglycemia awareness (Gold score).
      RESULTS: A total of 96 participants (mean diabetes duration 29 years) were
      randomized. Overall, biochemical hypoglycemia (<=3.0 mmol/L) decreased (53 +/- 63
      to 24 +/- 56 min/24 h; P = 0.004 [t test]) without deterioration in HbA1c.
      Hypoglycemia awareness improved (5.1 +/- 1.1 to 4.1 +/- 1.6; P = 0.0001 [t test])
      with decreased SH (8.9 +/- 13.4 to 0.8 +/- 1.8 episodes/patient-year; P = 0.0001
      [t test]). At 24 weeks, there was no significant difference in awareness
      comparing CSII with MDI (4.1 +/- 1.6 vs. 4.2 +/- 1.7; difference 0.1; 95% CI -0.6
      to 0.8) and RT with SMBG (4.3 +/- 1.6 vs. 4.0 +/- 1.7; difference -0.3; 95% CI 
      1.0 to 0.4). Between-group analyses demonstrated comparable reductions in SH,
      fear of hypoglycemia, and insulin doses with equivalent HbA1c. Treatment
      satisfaction was higher with CSII than MDI (32 +/- 3 vs. 29 +/- 6; P = 0.0003 [t
      test]), but comparable with SMBG and RT (30 +/- 5 vs. 30 +/- 5; P = 0.79 [t
      test]). CONCLUSIONS: Hypoglycemia awareness can be improved and recurrent SH
      prevented in long-standing type 1 diabetes without relaxing HbA1c. Similar
      biomedical outcomes can be attained with conventional MDI and SMBG regimens
      compared with CSII/RT, although satisfaction was higher with CSII.

PMID- 24854043
TI  - Networks development between nicotinic chemical probes and Ca9-22 oral cancer
      cells by general proteomics analyses.
AB  - Tobacco includes thousands of chemicals such as nicotine, which causes numerous
      diseases including oral cancer. We synthesized nicotinic acid based probes by
      chemical modification to identify the proteins expressed by the oral cancer cell
      line Ca9-22 that interact with the nicotinic functional group. Proteins belonging
      to human oral squamous cell carcinoma were pulled down by a probe carrier based
      on nicotinic acid, which was reacted with 3-aminopropyltriethoxysilane to compose
      nicotinic acid linked 3-aminopropyltriethoxysilane exposed on the SiO2 surface.
      Oral cancer cell lysates were incubated with the nicotinic acid chemical probes
      to identify the interactions between the nicotinic group and oral cancer cell
      line extracted proteins. The interactions between the chemical probes and
      proteins identified as their targets were confirmed by consulting chemicals
      databases. Interestingly, chaperone proteins (e.g., heat-shock proteins and
      endoplasmin) that were found to interact with nicotinic acid were identified as
      binding partners in ribosomal and nucleosome assembly complexes. 

PMID- 24854044
TI  - [Medication adherence of 65 patients in hemodialysis in Togo].
AB  - OBJECTIVE: The aim of this study was to assess adherence in people on
      hemodialysis and determine the factors of poor adherence. MATERIAL AND METHODS:
      This cross-sectional study took place throughout the month of September, 2012, in
      the hemodialysis center of the Sylvanus Olympio University Hospital, the only
      such center in Togo. RESULTS: The study included 65 patients, with a mean age of
      49.5 years (range: 22 to 77 years), more often men (sex ratio: 1.82) and married
      (74 %). More than half (58%) had completed secondary education, while 73%
      belonged to the least advantaged socioeconomic class; 61 (94%) had health
      insurance, and 57% had been on dialysis for 1 to 4 years. The compliance rate was
      11%. The main factors associated with good adherence were marital status (p =
      0.0339) and the patient's general health status (p = 0.001). Treatment fatigue (p
      = 0.0347), forgetfulness (p = 0.0001), dosage forms and drug characteristics (p =
      0.0198) were all factors of noncompliance. Therapeutic non-compliance was
      proportional to the number of drugs prescribed (p = 0.4263). CONCLUSION:
      Adherence in hemodialysis patients in Togo is very poor.

PMID- 24854045
TI  - Majewski syndrome (short-rib polydactyly syndrome type II): Prenatal diagnosis
      and histological features of chondral growth plate, liver and kidneys.
AB  - The Majewski syndrome or short rib-polydactyly syndrome (SRPS) type II is a
      lethal skeletal dysplasia characterized by severe IUGR (intrauterine growth
      restriction) and dysmorphic face, polydactyly, relatively proportionate head size
      at birth with later progression to microcephaly. A case of second trimester
      ultrasound diagnosis of SRPS type II is reported with review of the medical
      record of previous observed cases. Postmortem examination and radiogram confirmed
      the clinical diagnosis. Histological examination of the femoral epypheseal
      chondral plate showed an expanded and irregular hypertrophic zone. Moreover,
      characteristic cortico-medullary cysts of both kidneys and portal fibrosis were
      also demonstrated; findings consistent with the broad phenotypic spectrum of this
      rare skeletal disease. 

PMID- 24854046
TI  - Carotid artery calcification is associated with deep cerebral microbleeds.
AB  - BACKGROUND/AIMS: The aim of the present study was to determine the association
      between arterial calcification and cerebral microbleeds (CMB) relative to their
      distribution. METHODS: We identified 834 consecutive patients with acute ischemic
      stroke or transient ischemic attack who underwent CT angiography and
      susceptibility-weighted imaging. RESULTS: Internal carotid artery (ICA)
      calcification and CMB were found in 660 patients (79.1%) and 335 patients
      (40.2%), respectively. ICA calcification was independently associated with CMB of
      any location (odds ratio, OR, 2.86, 95% CI 2.01-4.08, p < 0.0001). The
      association between calcification and deep CMB was stronger (OR 3.51, 95% CI 2.39
      5.14, p < 0.0001). However, ICA calcification was not associated with CMB in a
      strictly lobar area. CONCLUSION: ICA calcification is an independent risk factor
      for deep CMB but not for a strictly lobar CMB. Our findings might contribute to
      the elucidation of the pathogenesis of cerebral small vessel disease.

PMID- 24854047
TI  - iTRAQ-based proteomic profiling of the marine medaka (Oryzias melastigma) gonad
      exposed to BDE-47.
AB  - A recent study demonstrated that 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) may
      have an adverse effect on the reproduction in marine medaka (Oryzias melastigma),
      but the molecular mechanisms remain largely unknown. In this study, we
      investigated the protein expression profiles of male and female gonads of O.
      melastigma exposed to dietary BDE-47 at two dosages (0.65 and 1.30 MUg/g/day,
      respectively) for 21 days. Extracted proteins were labeled with iTRAQ and
      analyzed on a MALDI TOF/TOF analyzer, as results, 133 and 144 unique proteins
      were identified in testis and ovary, respective, and they exerted dose- and sex
      dependent expression patterns. In testis, among the 42 differentially expressed
      proteins; down-regulation of histone variants and parvalbumins implicated BDE-47
      may disrupt the spermatogenesis and induce sterility in fishes. In ovary, 38
      proteins were differentially expressed; the elevation of vitellogenins and
      apolipoprotein A-I expression indicated BDE-47 acts as an estrogen-mimicking
      compound and led to reproductive impairment in O. melastigma.

PMID- 24854048
TI  - Origins and neurochemical complexity of preganglionic neurons supplying the
      superior cervical ganglion in the domestic pig.
AB  - The superior cervical ganglion (SCG) is a center of sympathetic innervation of
      all head and neck organs. SCG sympathetic preganglionic neurons (SPN) were found
      in the nucleus intermediolateralis pars principalis (IMLpp), the nucleus
      intermediolateralis pars funicularis (IMLpf), the nucleus intercalatus spinalis
      (IC), and the nucleus intercalatus spinalis pars paraependymalis (ICpe). Despite
      its importance, little is known of SCG innervation and chemical coding in the
      laboratory pig, a model that is physiologically and anatomically representative
      of humans. Here in our study, we established the distribution and chemical coding
      of Fast Blue (FB) retrogradely labelled SPN innervating porcine SCG. After
      unilateral injection of FB retrograde tracer into the left SCG, labeled neurons
      were found solely on the ipsilateral side with approximately 98% located in Th1
      Th3 segments and predominantly distributed in the IMLpp and IMLpf. Neurochemical
      analysis revealed that approximately 80% of SPN were positive both to choline
      acetyltransferase (ChAT) and nitric oxide synthase (NOS) and were surrounded by a
      plethora of opioidergic and peptiergic nerve terminals. The results of our study
      provide a detailed description of the porcine preganglionic neuroarchitecture of
      neurons controlling the SCG, setting the stage for further studies concerning SPN
      plasticity under experimental/pathological conditions.

PMID- 24854050
TI  - Magnesium is not consistently neuroprotective for perinatal hypoxia-ischemia in
      term-equivalent models in preclinical studies: a systematic review.
AB  - There is an important unmet need to further improve the outcome of neonatal
      encephalopathy in term infants. Meta-analyses of large controlled trials now
      suggest that maternal magnesium sulfate (MgSO4) therapy is associated with a
      reduced risk of cerebral palsy and gross motor dysfunction after premature birth,
      but that it has no effect on death or disability. Because of this inconsistency,
      it remains controversial whether MgSO4 is clinically neuroprotective and, thus,
      it is unclear whether it would be appropriate to test MgSO4 for treatment of
      encephalopathy in term infants. We therefore systematically reviewed the
      preclinical evidence for neuroprotection with MgSO4 before or after hypoxic
      ischemic encephalopathy (HIE) in term-equivalent perinatal and adult animals. The
      outcomes were highly inconsistent between studies. Although there were
      differences in dose and timing of administration, there was evidence that
      beneficial effects of MgSO4 were associated with confounding mild hypothermia
      and, strikingly, the studies that included rigorous maintenance of environmental
      temperature or body temperature consistently suggested a lack of effect. On
      balance, these preclinical studies suggest that peripherally administered MgSO4
      is unlikely to be neuroprotective. Rigorous testing in translational animal
      models of perinatal HIE is needed before MgSO4 should be considered in clinical
      trials for encephalopathy in term infants.

PMID- 24854049
TI  - Inpatient obesity intervention with postdischarge telephone follow-up: A
      randomized trial.
AB  - BACKGROUND: Obesity-related comorbidities frequently contribute to acute illness.
      Obesity interventions during hospitalization are not often utilized but may be
      effective. OBJECTIVE: To examine whether inpatient weight loss intervention with
      postdischarge follow-up results in weight loss at 6 months when compared to
      control. DESIGN: Prospective, randomized controlled trial. SETTING: Academic
      medical center in Chicago, Illinois. PATIENTS: Obese adult inpatients.
      INTERVENTION: Intervention subjects viewed a weight education video, underwent
      personalized counseling, and set specific weight loss, dietary, and fitness goals
      prior to discharge. All participants were followed by phone over the subsequent 6
      months. The trial was unblinded to participants, physicians, and investigators.
      MEASUREMENTS: Primary outcome was weight change between groups at 6 months.
      Weight change from baseline and waist-to-hip ratios (WHR) were also assessed.
      RESULTS: For 176 participants in the intention-to-treat analysis, mean baseline
      weight for the intervention group was 107.7 kg (standard deviation [SD]=16.7) and
      105.1 kg (SD=17.4) for controls. Mean weight loss at 6 months was 1.08 kg
      (SD=4.33) for intervention subjects and 1.35 kg (SD=3.65) among controls. There
      was no significant difference in weight loss between groups at 6 months (P=0.26).
      As-treated analysis yielded similar results. There were no differences in WHRs
      between the intervention and control at 6 months (0.04 vs 0.04, P=0.59).
      CONCLUSIONS: We found no difference in weight loss between the intervention and
      control groups at 6 months.

PMID- 24854051
TI  - An evaluation of novel biological activity in a crude extract from Hemerocallis
      fulva L. var. sempervirens M. Hotta.
AB  - Hemerocallis fulva L. var. sempervirens M. Hotta (kwanso) represents an
      exceptional resource for identifying and developing new phytomedicines for the
      treatment and prevention of disease. The aim of this study was to conduct a
      detailed investigation of the biological activities of kwanso. Our study resulted
      in four major findings. First, kwanso scavenges hydroxyl radicals generated by
      H(2)O(2)/UV light system in vitro in a dose-dependent manner. Second, hepatic
      glutathione levels were significantly increased when kwanso was orally
      administered to mice. Third, the oral administration of kwanso to mice showed a
      tendency to suppress hepatic injury induced by acetaminophen. Finally, kwanso
      slightly inhibited cytochrome P450 3A activity. These results provide useful
      evidence in support of the development of kwanso as a candidate raw material for
      the treatment and prevention of disease.

PMID- 24854052
TI  - Complexity and time asymmetry of heart rate variability are altered in acute
      mental stress.
AB  - We aimed to study the complexity and time asymmetry of short-term heart rate
      variability (HRV) as an index of complex neurocardiac control in response to
      stress using symbolic dynamics and time irreversibility methods. ECG was recorded
      at rest and during and after two stressors (Stroop, arithmetic test) in 70
      healthy students. Symbolic dynamics parameters (NUPI, NCI, 0V%, 1V%, 2LV%, 2UV%),
      and time irreversibility indices (P%, G%, E) were evaluated. Additionally, HRV
      magnitude was quantified by linear parameters: spectral powers in low (LF) and
      high frequency (HF) bands. Our results showed a reduction of HRV complexity in
      stress (lower NUPI with both stressors, lower NCI with Stroop). Pattern
      classification analysis revealed significantly higher 0V% and lower 2LV% with
      both stressors, indicating a shift in sympathovagal balance, and significantly
      higher 1V% and lower 2UV% with Stroop. An unexpected result was found in time
      irreversibility: significantly lower G% and E with both stressors, P% index
      significantly declined only with arithmetic test. Linear HRV analysis confirmed
      vagal withdrawal (lower HF) with both stressors; LF significantly increased with
      Stroop and decreased with arithmetic test. Correlation analysis revealed no
      significant associations between symbolic dynamics and time irreversibility.
      Concluding, symbolic dynamics and time irreversibility could provide independent
      information related to alterations of neurocardiac control integrity in stress
      related disease. 

PMID- 24854053
TI  - Rectal obliteration following stapled haemorrhoidopexy: a new endoscopic approach
      to restore luminal continuity.

PMID- 24854054
TI  - A hybrid indoor ambient light and vibration energy harvester for wireless sensor
      nodes.
AB  - To take advantage of applications where both light and vibration energy are
      available, a hybrid indoor ambient light and vibration energy harvesting scheme
      is proposed in this paper. This scheme uses only one power conditioning circuit
      to condition the combined output power harvested from both energy sources so as
      to reduce the power dissipation. In order to more accurately predict the
      instantaneous power harvested from the solar panel, an improved five-parameter
      model for small-scale solar panel applying in low light illumination is
      presented. The output voltage is increased by using the MEMS piezoelectric
      cantilever arrays architecture. It overcomes the disadvantage of traditional MEMS
      vibration energy harvester with low voltage output. The implementation of the
      maximum power point tracking (MPPT) for indoor ambient light is implemented using
      analog discrete components, which improves the whole harvester efficiency
      significantly compared to the digital signal processor. The output power of the
      vibration energy harvester is improved by using the impedance matching technique.
      An efficient mechanism of energy accumulation and bleed-off is also discussed.
      Experiment results obtained from an amorphous-silicon (a-Si) solar panel of 4.8 *
      2.0 cm2 and a fabricated piezoelectric MEMS generator of 11 * 12.4 mm2 show that
      the hybrid energy harvester achieves a maximum efficiency around 76.7%. 

PMID- 24854055
TI  - Virtual sensors for on-line wheel wear and part roughness measurement in the
      grinding process.
AB  - Grinding is an advanced machining process for the manufacturing of valuable
      complex and accurate parts for high added value sectors such as aerospace, wind
      generation, etc. Due to the extremely severe conditions inside grinding machines,
      critical process variables such as part surface finish or grinding wheel wear
      cannot be easily and cheaply measured on-line. In this paper a virtual sensor for
      on-line monitoring of those variables is presented. The sensor is based on the
      modelling ability of Artificial Neural Networks (ANNs) for stochastic and non
      linear processes such as grinding; the selected architecture is the Layer
      Recurrent neural network. The sensor makes use of the relation between the
      variables to be measured and power consumption in the wheel spindle, which can be
      easily measured. A sensor calibration methodology is presented, and the levels of
      error that can be expected are discussed. Validation of the new sensor is carried
      out by comparing the sensor's results with actual measurements carried out in an
      industrial grinding machine. Results show excellent estimation performance for
      both wheel wear and surface roughness. In the case of wheel wear, the absolute
      error is within the range of microns (average value 32 MUm). In the case of
      surface finish, the absolute error is well below Ra 1 MUm (average value 0.32
      MUm). The present approach can be easily generalized to other grinding
      operations. 

PMID- 24854056
TI  - Remote assessment of cultural heritage environments with wireless sensor array
      networks.
AB  - The logistics and cost of environmental monitoring can represent challenges for
      heritage managers, partly because of the sheer number of environmental parameters
      to consider. There is a need for a system, capable of monitoring the holistic
      impact of the environment on cultural materials while remaining relatively easy
      to use and providing remote access. This paper describes a dosimetric system
      based on piezoelectric quartz crystal technology. The prototype sensing module
      consists of an array of piezoelectric quartz crystals (PQC) coated with different
      metals (Fe, Cu, Ni and Sn) and includes a temperature and relative humidity
      sensor. The communication module involves an 802.15.4 low-power radio and a GPRS
      gateway which allows real time visualisation of the measurements online. An
      energy management protocol ensures that the system consumes very low power
      between measurements. The paper also describes the results and experiences from
      two heritage field deployments, at Apsley House in London, UK, and at the Royal
      Palaces of Abomey in Benin. Evaluation of PQC measurements, temperature, relative
      humidity and the rate of successful transmission over the communication systems
      are also reported. 

PMID- 24854057
TI  - Intelligent prediction of fan rotation stall in power plants based on pressure
      sensor data measured in-situ.
AB  - Blower and exhaust fans consume over 30% of electricity in a thermal power plant,
      and faults of these fans due to rotation stalls are one of the most frequent
      reasons for power plant outage failures. To accurately predict the occurrence of
      fan rotation stalls, we propose a support vector regression machine (SVRM) model
      that predicts the fan internal pressures during operation, leaving ample time for
      rotation stall detection. We train the SVRM model using experimental data
      samples, and perform pressure data prediction using the trained SVRM model. To
      prove the feasibility of using the SVRM model for rotation stall prediction, we
      further process the predicted pressure data via wavelet-transform-based stall
      detection. By comparison of the detection results from the predicted and measured
      pressure data, we demonstrate that the SVRM model can accurately predict the fan
      pressure and guarantee reliable stall detection with a time advance of up to
      0.0625 s. This superior pressure data prediction capability leaves significant
      time for effective control and prevention of fan rotation stall faults. This
      model has great potential for use in intelligent fan systems with stall
      prevention capability, which will ensure safe operation and improve the energy
      efficiency of power plants. 

PMID- 24854058
TI  - A SAW-based chemical sensor for detecting sulfur-containing organophosphorus
      compounds using a two-step self-assembly and molecular imprinting technology.
AB  - This paper presents a new effective approach for the sensitive film deposition of
      surface acoustic wave (SAW) chemical sensors for detecting organophosphorus
      compounds such as O-ethyl-S-2-diisopropylaminoethyl methylphosphonothiolate (VX)
      containing sulfur at extremely low concentrations. To improve the adsorptive
      efficiency, a two-step technology is proposed for the sensitive film preparation
      on the SAW delay line utilizing gold electrodes. First, mono[6-deoxy-6
      [(mercaptodecamethylene)thio]]-beta-cyclodextrin is chosen as the sensitive
      material for VX detection, and a ~2 nm-thick monolayer is formed on the SAW delay
      line by the binding of Au-S. This material is then analyzed by atomic force
      microscopy (AFM). Second, the VX molecule is used as the template for molecular
      imprinting. The template is then removed by washing the delay line with ethanol
      and distilled water, thereby producing the sensitive and selective material for
      VX detection. The performance of the developed SAW sensor is evaluated, and
      results show high sensitivity, low detection limit, and good linearity within the
      VX concentration of 0.15-5.8 mg/m3. The possible interactions between the film
      and VX are further discussed. 

PMID- 24854059
TI  - Ultrasonic lens based on a subwavelength slit surrounded by grooves.
AB  - The lensing capabilities of a single subwavelength slit surrounded by a finite
      array of grooves milled into a brass plate is presented. The modulation of the
      beam intensity of this ultrasonic lens can be adjusted by varying the groove
      depth. Numerical simulations as well as experimental validations at 290 kHz are
      shown. The experimental results are in good agreement with the numerical
      simulations. This system is believed to have potential applications for medical
      ultrasound fields such as tomography and therapy. 

PMID- 24854060
TI  - Functionality enhancement of industrialized optical fiber sensors and system
      developed for full-scale pavement monitoring.
AB  - Pavements always play a predominant role in transportation. Health monitoring of
      pavements is becoming more and more significant, as frequently suffering from
      cracks, rutting, and slippage renders them prematurely out of service. Effective
      and reliable sensing elements are thus in high demand to make prognosis on the
      mechanical properties and occurrence of damage to pavements. Therefore, in this
      paper, various types of functionality enhancement of industrialized optical fiber
      sensors for pavement monitoring are developed, with the corresponding operational
      principles clarified in theory and the performance double checked by basic
      experiments. Furthermore, a self-healing optical fiber sensing network system is
      adopted to accomplish full-scale monitoring of pavements. The application of
      optical fiber sensors assembly and self-healing network system in pavement has
      been carried out to validate the feasibility. It has been proved that the
      research in this article provides a valuable method and meaningful guidance for
      the integrity monitoring of civil structures, especially pavements. 

PMID- 24854061
TI  - An optimal current observer for predictive current controlled buck DC-DC
      converters.
AB  - In digital current mode controlled DC-DC converters, conventional current sensors
      might not provide isolation at a minimized price, power loss and size. Therefore,
      a current observer which can be realized based on the digital circuit itself, is
      a possible substitute. However, the observed current may diverge due to the
      parasitic resistors and the forward conduction voltage of the diode. Moreover,
      the divergence of the observed current will cause steady state errors in the
      output voltage. In this paper, an optimal current observer is proposed. It
      achieves the highest observation accuracy by compensating for all the known
      parasitic parameters. By employing the optimal current observer-based predictive
      current controller, a buck converter is implemented. The converter has a
      convergently and accurately observed inductor current, and shows preferable
      transient response than the conventional voltage mode controlled converter.
      Besides, costs, power loss and size are minimized since the strategy requires no
      additional hardware for current sensing. The effectiveness of the proposed
      optimal current observer is demonstrated experimentally. 

PMID- 24854062
TI  - Peritoneal cytology: a risk factor of recurrence for non-endometrioid endometrial
      cancer.
AB  - OBJECTIVE: We compared the impact of positive peritoneal cytology on prognosis
      between patients with endometrioid and non-endometrioid endometrial carcinoma.
      METHODS: We retrospectively reviewed the medical records of 490 patients
      diagnosed with endometrial cancer between 2000 and 2012. These patients were
      divided into two groups: endometrioid and non-endometrioid histologies. We
      compared the patients' baseline characteristics, tumor recurrence patterns, and
      survival to determine the prognostic factors and how they differed between the
      two groups. RESULTS: Of the included patients, 448 had endometrioid histology and
      42 had non-endometrioid histology. A total of 27 patients experienced tumor
      recurrence: 17 with endometrioid histology (4.0%) and 10 with non-endometrioid
      histology (23.8%). Compared to endometrioid type, non-endometrioid type exhibited
      higher rates of recurrence (p<0.01). Recurrence sites of the non-endometrioid
      group were mainly peritoneal seeding (p<0.01) and distant organ metastasis
      (p=0.02). Risk factors for tumor recurrence included patient age, stage of
      disease, and adjuvant treatment for endometrioid type. On the other hand, in
      cases of non-endometrioid endometrial cancer, positive peritoneal cytology was an
      independent prognostic factor regardless of tumor stage (HR, 15.34; 95% CI, 3.55
      66.25; p<0.01). Among cases with non-endometrioid histology, median recurrence
      free survival significantly differed between the negative peritoneal cytology
      group and the positive peritoneal cytology group (120 months versus 22 months,
      respectively; p<0.01). CONCLUSIONS: Positive peritoneal cytology is an
      independent prognostic factor for patients with non-endometrioid endometrial
      cancer.

PMID- 24854063
TI  - Induction of interleukin-8 and interleukin-12 in neonatal ovine lung following
      experimental inoculation of bovine respiratory syncytial virus.
AB  - This study aimed to determine the immunohistochemical expression of interleukin
      (IL)-1beta, tumour necrosis factor alpha (TNF)-alpha, interferon (IFN)-gamma, IL
      4, IL-6, IL-8, IL-10 and IL-12 and to measure the concentrations of these
      cytokines in lung tissue from lambs infected experimentally with bovine
      respiratory syncytial virus (BRSV). Lambs (n = 15) were inoculated at 2 days of
      age with 20 ml of viral inoculum (1.26 * 10(6) TCID50 per ml) or sterile medium
      (n = 15). Rectal temperature, pulse and respiratory rates were monitored daily in
      control and infected lambs. Lambs were killed and subject to necropsy examination
      at 1, 3, 5, 7 and 15 days post inoculation (dpi). There was a temporal
      association between pulmonary expression of these cytokines and lung pathology in
      BRSV-infected lambs. The cytokines IL-4 and IL-10 were not elevated, but there
      was a significant increase in IL-1beta, TNF-alpha, IFN-gamma and IL-6 proteins
      and labelled cells, suggesting that these cytokines may play a role in the
      biological response to BRSV infection and contribute to the development of lung
      lesions. There was also a significant increase in the cytokine concentration and
      number of immunolabelled cells expressing IL-8 and IL-12 in infected lungs,
      suggesting that these cytokines might be used as therapeutic targets in the
      management of BRSV, in conjunction with measures to combat the causative pathogen
      and prophylactic methods aimed at preventing infection.

PMID- 24854064
TI  - Forced treadmill running suppresses postincisional pain and inhibits upregulation
      of substance P and cytokines in rat dorsal root ganglion.
AB  - Exercise causes a variety of psychophysical effects (eg, alterations in pain
      sensation). Tissue injury induces mediator releases in the spinal cord resulting
      in pain hypersensitivity; however, the contribution of the dorsal root ganglion
      (DRG) is poorly understood. In this study, we tested if forced treadmill running
      can attenuate postoperative pain and alter substance P (SP) or proinflammatory
      cytokine level in the DRG by using a rat model of skin/muscle incision and
      retraction (SMIR). We evaluated mechanical sensitivity to von Frey stimuli (6 and
      15 g) and expression of SP, interleukin-1beta, and interleukin-6 in the DRG of
      sham-operated sedentary rats, SMIR sedentary rats, sham-operated rats with forced
      treadmill running, and SMIR rats with forced treadmill running. At postoperative
      day 8, trained rats ran for 5 days per week for 4 weeks on a treadmill 70
      minutes/d with an intensity of 18 m/min. On postoperative day 6, SMIR sedentary
      rats displayed a significant mechanical hypersensitivity that persisted until
      postoperative day 35. By comparison, SMIR-operated rats, which received forced
      treadmill running, exhibited a quick recovery from mechanical hypersensitivity.
      SMIR sedentary rats showed an upregulation of SP, interleukin-1beta, and
      interleukin-6 in the DRG at postoperative days 14 and 28, whereas SMIR-operated
      rats receiving forced treadmill running reversed this upregulation at
      postoperative day 28. We concluded that forced treadmill running alleviated
      persistent postincisional pain caused by SMIR surgery. This appears to be
      protective against postoperative pain, which probably relates to the downturn in
      excess SP, interleukin-1beta, and interleukin-6 in the DRG. PERSPECTIVE:
      Controlling the expression of SP, interleukin-6, and interleukin-1beta in the DRG
      can help manage postoperative pain. This finding could potentially help
      clinicians and physical therapists who seek to examine how exercise may attenuate
      postsurgical pain and its mechanism.

PMID- 24854065
TI  - Development and testing of painometer: a smartphone app to assess pain intensity.
AB  - Electronic and information technologies are increasingly being used to assess
      pain. This study aims to 1) introduce Painometer, a smartphone app that helps
      users to assess pain intensity, and 2) report on its usability (ie, user
      performance and satisfaction) and acceptability (ie, the willingness to use it)
      when it is made available to health care professionals and nonprofessionals.
      Painometer includes 4 well-known pain intensity scales: the Faces Pain Scale
      Revised, the numerical rating scale-11, the Coloured Analogue Scale, and the
      visual analog scale. Scores reported with these scales, when used in their
      traditional format, have shown to be valid and reliable. The app was tested in a
      sample of 24 health care professionals and 30 nonprofessionals. Two iterative
      usability cycles were conducted with a qualitative usability testing approach and
      a semistructured interview. The participants had an average of 10 years'
      experience in using computers. The domains measured were ease of use, errors in
      usage, most popular characteristics, suggested changes, and acceptability. Adding
      instructions and changing format and layout details solved the usability problems
      reported in cycle 1. No further problems were reported in cycle 2. Painometer has
      been found to be a useful, user-friendly app that may help to improve the
      accuracy of pain intensity assessment. PERSPECTIVE: Painometer, a smartphone app
      to assess pain intensity, shows good usability and acceptability properties when
      used by health care professionals and nonprofessionals.

PMID- 24854067
TI  - Morphological control of PbS grown on functionalized self-assembled monolayers by
      chemical bath deposition.
AB  - We have investigated the chemical bath deposition (CBD) of PbS on functionalized
      alkanethiolate self-assembled monolayers (SAMs) using time-of-flight secondary
      ion mass spectrometry (SIMS), X-ray photoelectron spectroscopy (XPS), and
      scanning electron microscopy. The deposition mechanism involves both cluster-by
      cluster and ion-by-ion growth. The dominant reaction pathway and the chemical
      composition and morphology of the deposited layer are dependent on both the SAM
      terminal group and the experimental conditions. On -COOH-terminated SAMs, three
      types of crystallites are observed: nanocrystals formed by heterogeneous ion-by
      ion growth, larger needle-like particles, and ~2 MUm particles deposited by
      homogeneous cluster-by-cluster deposition. The nanocrystals nucleate at Pb(2+)
      carboxylate surface complexes, and so strongly adhere to the substrate. On -OH-
      and -CH3-terminated SAMs, only the micrometer-sized particles are formed by a
      cluster-by-cluster deposition mechanism. These particles do not adhere strongly
      to the SAM surface and can be easily removed. SIMS and XPS analyses indicate that
      the larger needle-like crystals and micrometer-sized particles are composed of
      oxidized lead sulfide and lead oxides, while the nanocrystals are composed of
      >=85% PbS. Using sonication-assisted CBD, we demonstrate that PbS is deposited by
      ion-by-ion growth alone on -COOH-terminated SAMs. The deposited film is more
      compact with a smaller grain size and is >90% PbS.

PMID- 24854066
TI  - Can physicians be replaced with gynecological teaching women to train medical
      students in their first pelvic examination? A pilot study from Northern Sweden.
AB  - OBJECTIVE: The main objective was to gain a deeper understanding of how medical
      students perceive and experience learning from gynecological teaching women (GTW)
      instead of physicians in their first pelvic examination. A second aim was to
      describe how the women experience their roles as GTW. METHODS: Data were
      collected from individual interviews with 24 medical students from a medical
      school in Sweden and with 5 GTW. Discourse analysis was performed to acquire a
      deeper understanding of the informants' experiences and to understand social
      interactions. RESULTS: Five themes revealed in the medical students' experiences:
      "Hoping that anxiety will be replaced with security," "Meeting as equals creates
      a sense of calm," "Succeeding creates a sense of security for the future,"
      "Wanting but not having the opportunity to learn more," and "Feeling relieved and
      grateful." One theme revealed in the GTW experiences: "Hoping to relate in a
      trustworthy way." CONCLUSION: To replace physicians with GTW may facilitate the
      learning process and may also help medical students improve their communicative
      skills. Using GTW will hopefully further improve students' basic medical
      examination techniques and physician-patient relationships. PRACTICE
      IMPLICATIONS: Since GTW seems to increase self-confidence and skills of medical
      students performing their first pelvic examination we recommend that the use of
      GTW is considered in the training of medical students.

PMID- 24854068
TI  - Synthesis and structural studies of diorganotin(IV)-based coordination polymers
      bearing silaalkylphosphonate ligands and their transformation into colloidal
      domains.
AB  - The contribution of silaalkylphosphonic acids Me3SiCH2P(O)(OH)2 (1) and
      Me3SiC(CH3)2P(O)(OH)2 (2) as ligands was demonstrated for the first time by the
      isolation of new diorganotin(IV) phosphonates Et2Sn{OP(O)(OH)CH2SiMe3}(OSO2Me)
      (3), (Et2Sn)6{O3PC(CH3)2SiMe3}4(OSO2Me)4 (4), and Et2Sn(O3PCH2SiMe3) (5). X-ray
      crystallographic studies of 1-4 are presented. The structures of 1 and 2 adopt
      extended motifs by virtue of P-OH...O?P-type hydrogen bonding interactions. The
      molecular structure of 3 is composed of a dimer formed by bridging hydrogen
      phosphonate groups, while the sulfonate group appended on each tin atom acts in a
      MU2-bridging mode to afford the formation of one-dimensional coordination polymer
      featuring alternate eight-membered [-Sn-O-P-O-]2 and [-Sn-O-S-O-]2 rings. The
      asymmetric unit of 4 is composed of two crystallographically unique trinuclear
      tin phosphonate clusters with a Sn3(MU3-PO3)2 core linked together by
      coordinative association of a MU2-sulfonate group, while the remaining sulfonates
      are involved in the construction of a two-dimensional self-assembly. The identity
      of 1-5 in solution was established by IR and multinuclear ((1)H, (13)C, (31)P,
      (119)Sn) NMR spectroscopy. The presence of silaalkyl group in 5 imparts unusual
      solubility in hydrocarbon, aromatic, and ether solvents. As a consequence, the
      formation of colloidal particles of 5 featuring rodlike morphology was achieved
      by ultrasonication of a solution in ethanol-chloroform mixture. 

PMID- 24854069
TI  - Simultaneous determination of six index constituents and comparative analysis of
      four ethnomedicines from genus Gentiana using a UPLC-UV-MS method.
AB  - Many species from genus Gentiana (Gentianaceae) have a long history of
      applications as folk medicines in the world. A simple rapid UPLC-UV-MS/MS method
      has been developed and validated for the simultaneous determination of six index
      constituents (gentiopicroside, swertiamarin, loganic acid, sweroside, mangiferin
      and ferulic acid) from the four ethnomedicines (G. rigescens Franch. ex Hemsl.,
      G. rhodantha Franch. ex Hemsl., G. scabra Bunge and G. farreri Balf. f.). The
      UPLC analysis was performed on Shim-Pack XR-ODS III (150 * 2.0 mm, 2.2 um). The
      mobile phase was consisted of acetonitrile-0.1% formic acid water using gradient
      elution. The wavelength 242 nm was chose for the four iridoids as well as
      mangiferin and 320 nm was set for ferulic acid. Mass spectrometry was applied for
      identification and quantification for analytes with low concentration. All the
      regression equations revealed a good linear relationship (R(2)  > 0.9993).
      Accuracy and precision were all within the required limits. The chromatogram
      fingerprints analysis combined with principal component analysis showed the
      similarity values of the four species were <0.788 while the similarity values of
      G. scabra Bunge and G. rigescens Franch. ex Hemsl. were >0.993, which provided
      reasonable foundation for utilization and clinical application of the four
      ethnomedicines. This developed method appears to be a useful tool for quality
      control of the four ethnomedicines.

PMID- 24854070
TI  - Leukaemia: competition can be a good thing.

PMID- 24854075
TI  - Alternative splicing: aberrant splicing promotes colon tumour growth.

PMID- 24854076
TI  - Metastasis: shedding is no easy task.

PMID- 24854081
TI  - Cohesin in cancer: chromosome segregation and beyond.
AB  - Cohesin is an evolutionarily conserved, four-subunit complex that entraps DNA
      fibres within its ring-shaped structure. It was originally identified and named
      for its role in mediating sister chromatid cohesion, which is essential for
      chromosome segregation and DNA repair. Increasing evidence indicates that cohesin
      participates in other processes that involve DNA looping, most importantly,
      transcriptional regulation. Mutations in genes encoding cohesin subunits and
      other regulators of the complex have recently been identified in several types of
      tumours. Whether aneuploidy that results from chromosome missegregation is the
      major contribution of cohesin mutations to cancer progression is under debate. 

PMID- 24854084
TI  - Acute kidney injury in a single pediatric intensive care unit in Poland: a
      retrospective study.
AB  - BACKGROUND/AIMS: The recent improvements of management of patients in pediatric
      intensive care units (PICU) are associated with improved outcome. However, this
      decrease in mortality is associated with an increased number of children with
      acute kidney injury (AKI), especially in patients with multiorgan failure.
      METHODS: The report presents a retrospective analysis of 25 cases of AKI
      (assessed based on the pRIFLE criteria) in PICU within 7 years. RESULTS: AKI was
      diagnosed in 1.24% of all hospitalized children. AKI percentage duration (as
      compared to the total hospitalization time) in the children who died vs. the
      survivors was 79.55% vs. 46.19%, respectively (p<0.05). The mortality rate of AKI
      patients was 40% which was 4.4-times higher as compared to the total mortality
      rate in PICU. The final cumulative survival ratio (FCSR) of patients meeting the
      oliguria criterion (which was met in 48% of AKI patients) was 37% vs. 49% in non
      oliguric children. Averaged urine output values in the first week of
      hospitalization in the deceased vs. survivors were 1.49 vs. 2.57 ml/kg/h,
      respectively (p<0.05). CONCLUSIONS: Oliguria should not be considered as a
      sensitive parameter for AKI diagnosing in children below one year of age. A
      decreased mean urine output in the first week of PICU hospitalization (less than
      1.4 ml/kg/h) should be considered as a poor prognostic factor. In many cases AKI
      was diagnosed too infrequently and too late.

PMID- 24854082
TI  - Clinical implications of (epi)genetic changes in HPV-induced cervical
      precancerous lesions.
AB  - Infection of cervical epithelium with high-risk human papilloma virus (hrHPV)
      might result in productive or transforming cervical intraepithelial neoplasia
      (CIN) lesions, the morphology of which can overlap. In transforming CIN lesions,
      aberrations in host cell genes accumulate over time, which is necessary for the
      ultimate progression to cancer. On the basis of (epi)genetic changes, early and
      advanced transforming CIN lesions can be distinguished. This paves the way for
      new molecular tools for cervical screening, diagnosis and management of cervical
      cancer precursor lesions. 

PMID- 24854086
TI  - Electrochemical synthesis of a microporous conductive polymer based on a metal
      organic framework thin film.
AB  - A new approach to preparing 3D microporous conductive polymer has been
      demonstrated in the electrochemical synthesis of a porous polyaniline network
      with the utilization of a MOF thin film supported on a conducting substrate. The
      prepared porous polyaniline with well-defined uniform micropores of 0.84 nm
      exhibits a high BET surface area of 986 m(2) g(-1) and a high electric
      conductivity of 0.125 S cm(-1) when doped with I2, which is superior to existing
      porous conducting materials of porous MOFs, CMPs, and COFs.

PMID- 24854085
TI  - Nanoliter-scale protein crystallization and screening with a microfluidic droplet
      robot.
AB  - Large-scale screening of hundreds or even thousands of crystallization conditions
      while with low sample consumption is in urgent need, in current structural
      biology research. Here we describe a fully-automated droplet robot for nanoliter
      scale crystallization screening that combines the advantages of both automated
      robotics technique for protein crystallization screening and the droplet-based
      microfluidic technique. A semi-contact dispensing method was developed to achieve
      flexible, programmable and reliable liquid-handling operations for nanoliter
      scale protein crystallization experiments. We applied the droplet robot in large
      scale screening of crystallization conditions of five soluble proteins and one
      membrane protein with 35-96 different crystallization conditions, study of volume
      effects on protein crystallization, and determination of phase diagrams of two
      proteins. The volume for each droplet reactor is only ca. 4-8 nL. The protein
      consumption significantly reduces 50-500 fold compared with current
      crystallization stations. 

PMID- 24854083
TI  - Imaging hallmarks of cancer in living mice.
AB  - To comprehend the complexity of cancer, the biological characteristics acquired
      during the initiation and progression of tumours were classified as the
      'hallmarks of cancer'. Intravital microscopy techniques have been developed to
      study individual cells that acquire these crucial traits, by visualizing tissues
      with cellular or subcellular resolution in living animals. In this Review, we
      highlight the latest intravital microscopy techniques that have been used in
      living animals (predominantly mice) to unravel fundamental and dynamic aspects of
      various hallmarks of cancer. In addition, we discuss the application of
      intravital microscopy techniques to cancer therapy, as well as limitations and
      future perspectives for these techniques. 

PMID- 24854088
TI  - Topical corticosteroids minimise the risk of postinflammatory hyper-pigmentation
      after ablative fractional CO2 laser resurfacing in Asians.
AB  - Postinflammatory hyperpigmentation (PIH) is the most common adverse effect of
      laser treatment in dark-skinned individuals. Little is known whether PIH can be
      prevented or minimised. The objective of this study was to investigate the effect
      of short-term application of topical corticosteroids on the incidence of PIH
      after ablative fractional resurfacing in Asians. Forty subjects with skin
      phototype IV and atrophic acne scars were treated with a fractional CO2 laser on
      both sides of the face. Post-operatively, clobetasol propionate 0.05% ointment
      was applied to one randomly selected side of the face for the first 2 days,
      followed by an application of petrolatum jelly for the rest of the week
      (petrolatum was applied to the other side for 7 days). Assessments on the
      clinical outcome, the wound healing process and the occurrence of PIH were
      obtained once weekly for the first month and at 2 and 3 months post-treatment.
      The side of the face treated with petrolatum alone had significantly (p < 0.001)
      higher incidence of PIH (75%) after laser irradiation than the side of the face
      treated with topical corticosteroids and petrolatum (40%). The PIH occurring on
      the petrolatum-treated sides had significantly higher intensity (p < 0.001) and
      was spread over a significantly larger area (p < 0.001), compared with the
      corticosteroid- and petrolatum-treated sides. In conclusion, a short-term
      application of topical corticosteroids postoperatively is associated with a
      decreased risk of PIH after ablative fractional resurfacing. 

PMID- 24854087
TI  - Silencing of KIF14 interferes with cell cycle progression and cytokinesis by
      blocking the p27(Kip1) ubiquitination pathway in hepatocellular carcinoma.
AB  - Although it has been suggested that kinesin family member 14 (KIF14) has
      oncogenic potential in various cancers, including hepatocellular carcinoma (HCC),
      the molecular mechanism of this potential remains unknown. We aimed to elucidate
      the role of KIF14 in hepatocarcinogenesis by knocking down KIF14 in HCC cells
      that overexpressed KIF14. After KIF14 knockdown, changes in tumor cell growth,
      cell cycle and cytokinesis were examined. We also examined cell cycle regulatory
      molecules and upstream Skp1/Cul1/F-box (SCF) complex molecules. Knockdown of
      KIF14 resulted in suppression of cell proliferation and failure of cytokinesis,
      whereas KIF14 overexpression increased cell proliferation. In KIF14-silenced
      cells, the levels of cyclins E1, D1 and B1 were profoundly decreased compared
      with control cells. Of the cyclin-dependent kinase inhibitors, the p27(Kip1)
      protein level specifically increased after KIF14 knockdown. The increase in
      p27(Kip1) was not due to elevation of its mRNA level, but was due to inhibition
      of the proteasome-dependent degradation pathway. To explore the pathway upstream
      of this event, we measured the levels of SCF complex molecules, including Skp1,
      Skp2, Cul1, Roc1 and Cks1. The levels of Skp2 and its cofactor Cks1 decreased in
      the KIF14 knockdown cells where p27(Kip1) accumulated. Overexpression of Skp2 in
      the KIF14 knockdown cells attenuated the failure of cytokinesis. On the basis of
      these results, we postulate that KIF14 knockdown downregulates the expression of
      Skp2 and Cks1, which target p27(Kip1) for degradation by the 26S proteasome,
      leading to accumulation of p27(Kip1). The downregulation of Skp2 and Cks1 also
      resulted in cytokinesis failure, which may inhibit tumor growth. To the best of
      our knowledge, this is the first report that has identified the molecular target
      and oncogenic effect of KIF14 in HCC. 

PMID- 24854089
TI  - Suicide risk in long-term care facilities: a systematic review.
AB  - OBJECTIVE: Suicide risk is highest in later life; however, little is known about
      the risk of suicide among older adults in long-term care facilities (e.g.,
      nursing homes and assisted living facilities). The goal of this paper is to
      review and synthesize the descriptive and analytic epidemiology of suicide in
      long-term care settings over the past 25 years. METHODS: Four databases (PubMed,
      CINAHL Plus, Web of Knowledge, and EBSCOHost Academic Search Complete) were
      searched for empirical studies of suicide risk in nursing homes, assisted living,
      and other residential facilities from 1985 to 2013. Of the 4073 unique research
      articles identified, 37 were selected for inclusion in this review. RESULTS: Of
      the included reports, 21 were cross-sectional, 8 cohort, 3 qualitative, and 5
      intervention studies. Most studies indicate that suicidal thoughts (active and
      passive) are common among residents (prevalence in the past month: 5-33%),
      although completed suicide is rare. Correlates of suicidal thoughts among long
      term care residents include depression, social isolation, loneliness, and
      functional decline. Most studies examined only individual-level correlates of
      suicide, although there is suggestive evidence that organizational
      characteristics (e.g., bed size and staffing) may also be relevant. CONCLUSIONS:
      Existing research on suicide risk in long-term care facilities is limited but
      suggests that this is an important issue for clinicians and medical directors to
      be aware of and address. Research is needed on suicide risk in assisted living
      and other non-nursing home residential settings, as well as the potential role of
      organizational characteristics on emotional well-being for residents.

PMID- 24854090
TI  - Targeting cytotoxicity and tubulin polymerization by metal-carbene complexes on a
      purine tautomer platform.
AB  - This communication describes the synthesis, structural investigation and tubulin
      binding of purine rare imino-tautomer based Ag(i) and Hg(ii)-carbene complexes.
      These complexes exhibit cytotoxicity through tubulin interaction by binding to a
      site close to the GTP binding site. 

PMID- 24854091
TI  - Role of nuclear factor E2-related factor 2 (Nrf2) in epidermal differentiation.
AB  - Nuclear factor E2-related factor 2 (Nrf2) is one of the most important redox
      sensitive transcription factors regulating expression of antioxidative genes and
      cytoprotective enzymes, which constitute the cellular response to oxidative
      stress and xenobiotic damage. In this study, we investigated the functional role
      of Nrf2 during normal epidermal keratinocyte (NHEK) differentiation.
      Immunohistochemical staining showed that Nrf2 is expressed from basal to granular
      layer of epidermis. When cultured NHEKs were treated with 1.2 mM calcium, Nrf2
      expression was increased gradually in protein levels and Nrf2 translocated into
      the nucleus in a differentiation-dependent manner. When Nrf2 was overexpressed in
      NHEK by adenoviral transduction, the expression of the NHEK differentiation
      marker loricrin and keratin 10 was increased and overexpression of Nrf2 also
      increased the luciferase activity of loricrin in the absence of calcium. These
      results suggest that Nrf2 helps to promote the differentiation of epidermal
      keratinocytes. 

PMID- 24854092
TI  - Dose ranging, expanded acute toxicity and safety pharmacology studies for
      intravenously administered functionalized graphene nanoparticle formulations.
AB  - Graphene nanoparticle dispersions show immense potential as multifunctional
      agents for in vivo biomedical applications. Herein, we follow regulatory
      guidelines for pharmaceuticals that recommend safety pharmacology assessment at
      least 10-100 times higher than the projected therapeutic dose, and present
      comprehensive single dose response, expanded acute toxicology, toxicokinetics,
      and respiratory/cardiovascular safety pharmacology results for intravenously
      administered dextran-coated graphene oxide nanoplatelet (GNP-Dex) formulations to
      rats at doses between 1 and 500 mg/kg. Our results indicate that the maximum
      tolerable dose (MTD) of GNP-Dex is between 50 mg/kg <= MTD < 125 mg/kg, blood
      half-life < 30 min, and majority of nanoparticles excreted within 24 h through
      feces. Histopathology changes were noted at >=250 mg/kg in the heart, liver,
      lung, spleen, and kidney; we found no changes in the brain and no GNP-Dex related
      effects in the cardiovascular parameters or hematological factors (blood, lipid,
      and metabolic panels) at doses < 125 mg/kg. The results open avenues for pivotal
      preclinical single and repeat dose safety studies following good laboratory
      practices (GLP) as required by regulatory agencies for investigational new drug
      (IND) application.

PMID- 24854094
TI  - Tumor-specific delivery of siRNA using supramolecular assembly of hyaluronic acid
      nanoparticles and 2b RNA-binding protein/siRNA complexes.
AB  - Anticancer therapeutics delivering exogenous siRNA have been explored to suppress
      the tumor-associated genes, but several limitations of siRNA delivery such as
      tumor-targeted delivery, controlled siRNA release at the sites of interest, or
      instabilities of siRNA in physiological fluids should be preferentially addressed
      for its clinical applications. As an attempt to meet these criteria, we designed
      a supramolecular assembly, which was composed of cholesterol-bearing hyaluronic
      acid (HA-Chol) conjugates and 2b RNA-binding protein (2b)/siRNA complexes. In
      contrast to the traditional siRNA polyplexes using electrostatic interactions, HA
      Chol nanoparticles, as a results of self-assembly of HA-Chol conjugates, provide
      the hydrophobic core that acts as the container for 2b protein/siRNA complexes,
      where a high affinity of 2b protein for siRNA could neutralize the negative
      charged siRNA. Here, we investigated the potential of HA-Chol/2b/siRNA complexes
      as the siRNA carriers that provide encapsulation, protection, and targeted
      delivery of siRNA. The HA-Chol nanoparticles could selectively deliver 2b
      protein/siRNA complexes to the tumor cells with up-regulated CD44 receptors and
      suppress the expression of target gene. The pH-associated binding properties of
      siRNA for 2b proteins allowed the controlled release of siRNA in the endocytic
      compartments, and ultimately the released siRNA could obtain the RNAi acitivities
      in the cells, whereas the encapsulated 2b proteins still stayed within the HA
      Chol nanoparticles. Our delivery systems demonstrate the promising potential of
      the efficient siRNA carriers in the anticancer therapeutic applications. 

PMID- 24854093
TI  - The potential of label-free nonlinear optical molecular microscopy to non
      invasively characterize the viability of engineered human tissue constructs.
AB  - Nonlinear optical molecular imaging and quantitative analytic methods were
      developed to non-invasively assess the viability of tissue-engineered constructs
      manufactured from primary human cells. Label-free optical measures of local
      tissue structure and biochemistry characterized morphologic and functional
      differences between controls and stressed constructs. Rigorous statistical
      analysis accounted for variability between human patients. Fluorescence intensity
      based spatial assessment and metabolic sensing differentiated controls from
      thermally-stressed and from metabolically-stressed constructs. Fluorescence
      lifetime-based sensing differentiated controls from thermally-stressed
      constructs. Unlike traditional histological (found to be generally reliable, but
      destructive) and biochemical (non-invasive, but found to be unreliable) tissue
      analyses, label-free optical assessments had the advantages of being both non
      invasive and reliable. Thus, such optical measures could serve as reliable
      manufacturing release criteria for cell-based tissue-engineered constructs prior
      to human implantation, thereby addressing a critical regulatory need in
      regenerative medicine. 

PMID- 24854095
TI  - Engineering a vascular endothelial growth factor 165-binding heparan sulfate for
      vascular therapy.
AB  - The therapeutic use of VEGF165 to stimulate blood vessel formation for the
      treatment of peripheral arterial disease or cardiovascular-related disease has
      met with limited success. Here we describe an affinity-isolated heparan sulfate
      glycotherapeutic (HS7(+ve)) that binds to, and enhances the bioactivity of,
      VEGF165. Application of HS7(+ve) complexed with VEGF165 results in enhanced
      VEGF165-VEGFR2 interaction, prolonged downstream pErk1/2 signalling, and
      increased cell proliferation and tube formation in HUVECs, compared with VEGF165
      alone. The pro-angiogenic potential of HS7(+ve) was further assessed in vivo
      using the chick embryo chorioallantoic membrane (CAM) assay. Exogenous dosing
      with HS7(+ve) alone significantly enhanced the formation of new blood vessels
      with potencies comparable to VEGF165. These results demonstrate the potential for
      vascular therapy of glycotherapeutic agents targeted at augmenting the
      bioactivity of VEGF165.

PMID- 24854096
TI  - Palmitate-induced cell death and mitochondrial respiratory dysfunction in
      myoblasts are not prevented by mitochondria-targeted antioxidants.
AB  - BACKGROUND/AIMS: Deleterious effects of saturated fatty acids in skeletal muscle
      cells are well known but their impact on mitochondrial respiration has not been
      well studied. Mitochondrial oxidative damage has been implicated to play a role
      in their effect. The purpose of this study was to evaluate viability, mtDNA
      integrity and mitochondrial respiration in C2C12 myoblasts and myotubes exposed
      to palmitate and to test the effect of mitochondria-targeted antioxidants MitoQ
      and MitoTEMPOL in preventing palmitate-induced damage. METHODS: Cells were
      treated with tested compounds, mtDNA damage was detected by quantitative PCR and
      mitochondrial respiration was measured using an extracellular flux analyzer XF24.
      RESULTS: Palmitate caused mtDNA damage, which was associated with reduced
      mitochondrial respiration and cell death in myoblasts but not in myotubes.
      MitoTEMPOL was able to prevent palmitate-induced mtDNA damage in myoblasts but
      failed to prevent cell death. MitoQ did not show any protective effect and both
      compounds markedly inhibited mitochondrial respiration. CONCLUSION: Our results
      indicate that skeletal muscle progenitor cells could be the first target of the
      deleterious action of palmitate, as myoblasts appeared to be more sensitive to
      its effects than myotubes possibly in part due to a lower spare respiratory
      capacity in the former. Only MitoTEMPOL prevented palmitate-induced mtDNA damage
      but neither antioxidant was able to prevent cell death and both antioxidants had
      a marked negative effect on respiration.

PMID- 24854097
TI  - Expression patterns of neuroligin-3 and tyrosine hydroxylase across the brain in
      mate choice contexts in female swordtails.
AB  - Choosing mates is a commonly shared behavior across many organisms, with
      important fitness consequences. Variations in female preferences can be due in
      part to differences in neural and cellular activity during mate selection.
      Initial studies have begun to identify putative brain regions involved in mate
      preference, yet the understanding of the neural processes regulating these
      behaviors is still nascent. In this study, we characterized the expression of a
      gene involved in synaptogenesis and plasticity (neuroligin-3) and one that codes
      for the rate-limiting enzyme in dopamine biosynthesis (tyrosine hydroxylase; TH1)
      in the female Xiphophorus nigrensis (northern swordtail) brain as related to mate
      preference behavior. We exposed females to a range of different mate choice
      contexts including two large courting males (LL), two small coercive males (SS),
      and a context that paired a large courting male with a small coercive male (LS).
      Neuroligin-3 expression in a mate preference context (LS) showed significant
      correlations with female preference in two telencephalic areas (Dm and Dl), a
      hypothalamic nucleus (HV), and two regions associated with sexual and social
      behavior (POA and Vv). We did not observe any context- or behavior-specific
      changes in tyrosine hydroxylase mRNA expression concomitant with female
      preference in any of the brain regions examined. Analysis of TH and neuroligin-3
      expression across different brain regions showed that expression patterns varied
      with the male social environment only for neuroligin-3, where the density of
      correlated expression between brain regions was positively associated with mate
      choice contexts that involved a greater number of courting male phenotypes (LS
      and LL). This study identified regions showing presumed high levels of synaptic
      plasticity using neuroligin-3, implicating and supporting their roles in female
      mate preference, but we did not detect any relationship between tyrosine
      hydroxylase and mate preference with 30 min of stimulus presentation in X.
      nigrensis. These data suggest that information about potential mates is processed
      in select forebrain regions and the entire brain shows different degrees of
      correlated expression depending on the mate preference context.

PMID- 24854098
TI  - Vapor-condensation-assisted optical microscopy for ultralong carbon nanotubes and
      other nanostructures.
AB  - Here we present a simple yet powerful approach for the imaging of nanostructures
      under an optical microscope with the help of vapor condensation on their
      surfaces. Supersaturated water vapor will first form a nanometer-sized water
      droplet on the condensation nuclei on the surface of nanostructures, and then the
      water droplet will grow bigger and scatter more light to make the outline of the
      nanostructure be visible under dark-field optical microscope. This vapor
      condensation-assisted (VCA) optical microscopy is applicable to a variety of
      nanostructures from ultralong carbon nanotubes to functional groups, generating
      images with contrast coming from the difference in density of the condensation
      sites, and does not induce any impurities to the specimens. Moreover, this low
      cost and efficient technique can be conveniently integrated with other
      facilities, such as Raman spectroscope and so forth, which will pave the way for
      widespread applications. 

PMID- 24854100
TI  - Efficacy and predictors of EGFR tyrosine kinase inhibitors in Chinese advanced
      lung adenocarcinoma: analyses of 253 cases from a single institute.
AB  - The aim of this study was to analyze the efficacy according to EGFR status and
      predictors of TKIs in Chinese advanced lung adenocarcinoma patients in a single
      institute. We retrospectively enrolled 253 patients with advanced or recurrent
      adenocarcinoma and history of EGFR-TKI treatment attended at Beijing Chest
      Hospital in Beijing, China, from July 2007 to August 2012. Overall response rate
      (ORR), disease control rate (DCR), progression-free survival (PFS), and overall
      survival (OS) were analyzed according to EGFR status and in different treatment
      lines. The predictors of outcomes were also evaluated. Of all of the patients,
      the ORR was 36.0%, DCR was 66.0%, the median PFS time was 6.0 months, and the
      median OS time was 14.2 months. Compared with patients with EGFR wild type and
      EGFR status unknown, the ORR and PFS in patients with EGFR-activating mutations
      were significantly better (p < 0.001, p < 0.001; p < 0.001, p = 0.004,
      respectively). In patients harboring activating mutations, the ORR in first line
      and second line or beyond were 62.1%, 54.3%; DCR were 79.3%, 89.1%; PFS were 8.7
      months and 7.8 months (p = 0.633, 0319, 0.320, respectively). The multivariate
      analysis showed that EGFR mutations and nonsmoking were independent factors of
      better ORR. In Cox regression analysis, ECOG performance status (PS) 0-1,
      nonsmoking, low number of metastatic organs, EGFR-activating mutations were
      independent factors of longer PFS. ECOG PS 0-1 and low number of metastatic
      organs were independent factors of longer OS. In conclusion, patients harboring
      EGFR-activating mutations had better ORR and longer PFS in TKI treatment. There
      was no difference in the ORR and PFS in patients with activating mutations in the
      first line and the second line or beyond.

PMID- 24854099
TI  - Inhibition of tumor angiogenesis by interferon-gamma by suppression of tumor
      associated macrophage differentiation.
AB  - Tumor-associated macrophages (TAMs) differentiate from monocytes and are the M2
      polarized macrophages in most human tumors, secreting generous vascular
      endothelial growth factor (VEGF) to promote angiogenesis. Although it has been
      shown in vitro that interferon-gamma (IFN-gamma) can inhibit monocytes
      differentiating to M2 macrophages in the tumor microenvironment and switch TAMs
      from M2 into M1, suppressing the ability of secreting VEGF, its effects on TAMs
      in vivo remains unknown. Here we tried to examine the effects of IFN-gamma on the
      recruitment of monocyte/macrophage differentiation of TAMs and tumor angiogenesis
      in vivo. We built a gallbladder cancer model by inoculating subcutaneously the
      human gallbladder cancer cell line (GBC-SD) into BALB/C nude mice and injected
      the recombinant mouse IFN-gamma intratumorally. We found that in the IFN-gamma
      group, the number of monocytes/macrophages was significantly higher than that in
      the control group (p < 0.01), and TAM differentiation rate, which we defined as
      the number of TAMs / the number of monocytes/macrophages * 100%, mice-VEGF
      concentration, and microvessels density (MVD) were significantly lower than those
      in the control group (p < 0.01, p < 0.05, and p < 0.01). Our results suggest that
      IFN-gamma can induce monocytes/macrophages recruiting into the tumor
      microenvironment, but inhibit them, differentiating to TAMs in vivo, which may
      reduce the concentration of VEGF and angiogenesis in tumor.

PMID- 24854101
TI  - Clove extract inhibits tumor growth and promotes cell cycle arrest and apoptosis.
AB  - Cloves (Syzygium aromaticum) have been used as a traditional Chinese medicinal
      herb for thousands of years. Cloves possess antiseptic, antibacterial,
      antifungal, and antiviral properties, but their potential anticancer activity
      remains unknown. In this study, we investigated the in vitro and in vivo
      antitumor effects and biological mechanisms of ethyl acetate extract of cloves
      (EAEC) and the potential bioactive components responsible for its antitumor
      activity. The effects of EAEC on cell growth, cell cycle distribution, and
      apoptosis were investigated using human cancer cell lines. The molecular changes
      associated with the effects of EAEC were analyzed by Western blot and (qRT)-PCR
      analysis. The in vivo effect of EAEC and its bioactive component was investigated
      using the HT-29 tumor xenograft model. We identified oleanolic acid (OA) as one
      of the components of EAEC responsible for its antitumor activity. Both EAEC and
      OA display cytotoxicity against several human cancer cell lines. Interestingly,
      EAEC was superior to OA and the chemotherapeutic agent 5-fluorouracil at
      suppressing growth of colon tumor xenografts. EAEC promoted G0/G1 cell cycle
      arrest and induced apoptosis in a dose-dependent manner. Treatment with EAEC and
      OA selectively increased protein expression of p21(WAF1/Cip1) and gamma-H2AX and
      downregulated expression of cell cycle-regulated proteins. Moreover, many of
      these changes were at the mRNA level, suggesting transcriptional regulation by
      EAEC treatment. Our results demonstrate that clove extract may represent a novel
      therapeutic herb for the treatment of colorectal cancer, and OA appears to be one
      of the bioactive components.

PMID- 24854102
TI  - Inhibition of Beclin 1 expression enhances cisplatin-induced apoptosis through a
      mitochondrial-dependent pathway in human ovarian cancer SKOV3/DDP cells.
AB  - The purpose of this study was to determine the influence of autophagy on
      cisplatin-induced ovarian cancer SKOV3/DDP cell line death through regulation of
      the expression of the autophagy gene, Beclin 1, and to explore the potential
      mechanism underlying the relationship between autophagy and apoptosis. When
      compared with a blank control group, the proportion of apoptotic cells undergoing
      Beclin 1 interfering increased significantly after cisplatin treatment,
      accompanied by reduction in mitochondrial membrane potential, increase in
      activities of caspase-9/3 and cytoplasmic cytochrome C, elevation of Bax
      expression, and reduction in Bcl-2 expression. However, the proportion of
      apoptotic cells with Beclin 1 overexpression reduced. These findings suggest that
      Beclin 1 plays an important role in the regulation of potent antitumor activity
      through a mitochondrial-dependent pathway in SKOV3/DDP cell line, and inhibition
      of Beclin 1 expression may become a new target for the sensitization therapy of
      ovarian cancer with cisplatin.

PMID- 24854103
TI  - SiRNA-mediated flotillin-2 (Flot2) downregulation inhibits cell proliferation,
      migration, and invasion in gastric carcinoma cells.
AB  - The flotillin (Flot) protein family has been demonstrated to be involved in the
      development and progression of various cancers. However, the role of Flot2 in
      gastric carcinomas remains unknown. The present study aimed to investigate the
      clinical significance and the role of Flot2 in gastric carcinomas. Data of tissue
      microarray including 90 cases of gastric carcinoma samples and their matched
      adjacent tissues showed that, among 90 cases of adjacent tissues, 65 cases showed
      no Flot2 expression, and 25 cases showed low expression of Flot2, and its
      positive expression rate was only 38.5% (25/90); however, among 90 cases of
      gastric carcinomas, 6 cases showed no Flot2 expression, 26 cases showed low Flot2
      expression, 28 cases showed moderate expression of Flot2, and 30 cases showed
      high expression of Flot2, and its positive expression rate was 93.3% (84/90).
      Moreover, the Flot2 expression was significantly associated with the histological
      grade, depth of invasion, lymph node metastasis, and TNM stage. Furthermore, data
      of survival analysis suggested that Flot2 protein expression was an independent
      prognostic factor of poor survival. After that, Flot2-specific siRNA was used to
      decrease the Flot2 expression in gastric cancer AGS and SGC7901 cells. Forced
      downregulation of Flot2 remarkably inhibited cellular proliferation, migration,
      and invasion in gastric carcinoma cells. In conclusion, the present study
      suggests that the Flot2 protein expression is significantly correlated with
      cancer progression and poor prognosis in gastric carcinomas, probably due to its
      role in the regulation of cell proliferation, migration, and invasion in gastric
      carcinoma cells.

PMID- 24854104
TI  - The novel HDAC inhibitor OBP-801/YM753 enhances the effects of 5-fluorouracil
      with radiation on esophageal squamous carcinoma cells.
AB  - Histone deacetylase (HDAC) inhibitors have been shown to enhance the effects of 5
      fluorouracil (5-FU) against various cancer cells; however, no report has shown
      that an HDAC inhibitor may enhance the effects of 5-FU with radiation. Therefore,
      we investigated whether the novel HDAC inhibitor OBP-801/YM753 could enhance the
      effects of 5-FU with radiation on esophageal squamous carcinoma KYSE170 cells.
      The inhibition of the cell growth was significantly stronger with the combination
      of OBP-801/YM753 with 5-FU than with the 5-FU treatment only. Furthermore,
      inhibition of the colony formation was the most effective with the combined
      treatment of OBP-801/YM753, 5-FU, and radiation. Western blot analysis showed
      that OBP-801/YM753 suppressed the expression of thymidylate synthase induced by 5
      FU. Therefore, this three-combined therapy is promising for patients with
      esophageal squamous carcinoma.

PMID- 24854105
TI  - Reliability of measurements of tongue and hand strength and endurance using the
      Iowa Oral Performance Instrument with elderly adults.
AB  - PURPOSE: This study investigated the reliability of tongue and hand strength and
      endurance measurements in old adults using the Iowa Oral Performance Instrument
      (IOPI). METHOD: Thirty aged-care residents (6 males and 24 females) aged 79-97
      years were tested on four occasions two weeks apart to determine test-retest
      reliability. The primary outcome measures were isometric anterior and posterior
      tongue and hand strength (best of three trials) and isometric tongue and hand
      endurance time at 50% of maximal strength. RESULTS: Changes in the mean between
      sessions for tongue and hand strength indicated acceptable (< 10%) reliability
      particularly with familiarisation. The within-subject variation (mean-typical
      error expressed as a coefficient of variation, CV) indicated higher than
      acceptable variation for anterior and posterior tongue and hand strength. Intra
      class correlations (ICC) indicated moderate to strong reliability for anterior
      (ICC 0.58-0.77) and posterior (ICC 0.77-0.84) tongue strength and hand strength
      (ICC 0.79-0.96). No tongue or hand endurance measures were regarded as reliable.
      CONCLUSION: These findings indicate that overall tongue and hand strength values
      demonstrate acceptable reliability in the elderly, especially where
      familiarisation with the IOPI is provided. Further investigation to reduce
      sources of variability in tongue endurance measurements is warranted.

PMID- 24854106
TI  - Hydrogen bond directed epoxidation: diastereoselective olefinic oxidation of
      allylic alcohols and amines.
AB  - This article compares the diastereoselective epoxidation of acyclic and cyclic
      allylic alcohols, with the chemo- and diastereoselective olefinic oxidation of a
      range of acyclic and cyclic allylic amines. The diastereoselectivity in these
      systems is compared and a discussion about the origin of this high
      diastereocontrol is also presented. The ammonium directed epoxidation methodology
      has been extended to more complex substrates and representative applications of
      this protocol in natural product synthesis are also summarised. 

PMID- 24854107
TI  - Bioenergetic and proteolytic defects in fibroblasts from patients with sporadic
      Parkinson's disease.
AB  - BACKGROUND: Parkinson's disease (PD) is a complex disease and the current
      interest and focus of scientific research is both investigating the variety of
      causes that underlie PD pathogenesis, and identifying reliable biomarkers to
      diagnose and monitor the progression of pathology. Investigation on pathogenic
      mechanisms in peripheral cells, such as fibroblasts derived from patients with
      sporadic PD and age/gender matched controls, might generate deeper understanding
      of the deficits affecting dopaminergic neurons and, possibly, new tools
      applicable to clinical practice. METHODS: Primary fibroblast cultures were
      established from skin biopsies. Increased susceptibility to the PD-related toxin
      rotenone was determined with apoptosis- and necrosis-specific cell death assays.
      Protein quality control was evaluated assessing the efficiency of the Ubiquitin
      Proteasome System (UPS) and protein levels of autophagic markers. Changes in
      cellular bioenergetics were monitored by measuring oxygen consumption and
      glycolysis-dependent medium acidification. The oxido-reductive status was
      determined by detecting mitochondrial superoxide production and oxidation levels
      in proteins and lipids. RESULTS: PD fibroblasts showed higher vulnerability to
      necrotic cell death induced by complex I inhibitor rotenone, reduced UPS function
      and decreased maximal and rotenone-sensitive mitochondrial respiration. No
      changes in autophagy and redox markers were detected. CONCLUSIONS: Our study
      shows that increased susceptibility to rotenone and the presence of proteolytic
      and bioenergetic deficits that typically sustain the neurodegenerative process of
      PD can be detected in fibroblasts from idiopathic PD patients. Fibroblasts might
      therefore represent a powerful and minimally invasive tool to investigate PD
      pathogenic mechanisms, which might translate into considerable advances in
      clinical management of the disease.

PMID- 24854108
TI  - gHRV: Heart rate variability analysis made easy.
AB  - In this paper, the gHRV software tool is presented. It is a simple, free and
      portable tool developed in python for analysing heart rate variability. It
      includes a graphical user interface and it can import files in multiple formats,
      analyse time intervals in the signal, test statistical significance and export
      the results. This paper also contains, as an example of use, a clinical analysis
      performed with the gHRV tool, namely to determine whether the heart rate
      variability indexes change across different stages of sleep. Results from tests
      completed by researchers who have tried gHRV are also explained: in general the
      application was positively valued and results reflect a high level of
      satisfaction. gHRV is in continuous development and new versions will include
      suggestions made by testers. 

PMID- 24854109
TI  - Trying to Raise (Low) Math Achievement and to Promote (Rigorous) Policy
      Evaluation in Italy: Evidence From a Large-Scale Randomized Trial.
AB  - BACKGROUND: Italy is a country showing low math achievement, especially in the
      Southern regions. Moreover, national student assessments are recent and rigorous
      policy evaluation is lacking. This study presents the results of one of the first
      randomized controlled trials implemented in Italian schools in order to measure
      the effects of a professional development (PD) program for teachers on student
      math achievement. The program was already at scale when it was being evaluated.
      OBJECTIVE: Assessing the effects of a PD program for math teachers on their
      students' achievement and making suggestions for future policy evaluations.
      DESIGN: A large-scale clustered randomized control trial has been conducted. It
      involves 175 lower secondary schools (sixth - eighth grade) in four among the
      Italian lowest performing regions. Alongside national standard math assessments,
      the project collected a wide amount of information. SUBJECTS: Math in lower
      secondary schools. MEASURES: Math achievement as measured by standardized tests
      provided by the National Education Assessment Institute (Istituto Nazionale per
      la Valutazione del Sistema di Istruzione e Formazione); teacher and student
      practices and attitudes collected through questionnaires. RESULTS: Findings
      suggest that the program had no significant impact on math scores during the
      first year (when the program was held). Nonetheless some heterogeneity was
      detected, as the treatment does seem "to work" with middle-aged teachers.
      Moreover, effects on teaching practice and student attitudes appear. CONCLUSION:
      Some effects attributable to the intervention have been detected. Moreover, this
      project shows that a rigorous approach to evaluation is feasible also in a
      context lacking attention towards evidence-based policies, such the Italian
      school system.

PMID- 24854111
TI  - [{Cu(IPr)}2(MU-OH)][BF4]: synthesis and halide-free CuAAC catalysis.
AB  - The preparation under protic conditions of the first MU-hydroxo dicopper(I)-NHC
      complex is reported. Its application as a CuAAC catalyst was investigated,
      evidencing a remarkable enhancement of catalytic efficiency in the presence of
      4,7-dichloro-1,10-phenanthroline and highlighting the beneficial effect of the
      absence of coordinating halides.

PMID- 24854110
TI  - Rosuvastatin inhibits TIMP-2 and promotes myocardial angiogenesis.
AB  - BACKGROUND: Angiogenesis is usually driven by inflammation. Matrix
      metalloproteinases MMP-3 and MMP-9 and tissue inhibitors of metalloproteinases
      TIMP-1 and TIMP-2 are implicated in vascular remodeling. TIMP-2 exhibits
      antiangiogenic properties. Statins show benefits that are additional to lipid
      lowering including pro- and antiangiogenic properties. Atherosclerotic lesions in
      the coronary arteries have been well studied, but less is known about the fine
      terminal branches of the myocardial vasculature. METHODS: To examine this, we
      studied rosuvastatin (RSV) treatment in ApoE knockout (ApoE(-/-)) mice fed a high
      cholesterol (HC) diet. Hearts from ApoE(-/-) mice on a normal diet, HC diet and
      HC diet with RSV were harvested to determine MMP-3, MMP-9, TIMP-1, TIMP-2,
      vascular endothelial growth factor (VEGF)-A and estrogen receptor-alpha (ER
      alpha) mRNA. RESULTS: RSV inhibited TIMP-1 and TIMP-2 expression and enhanced
      myocardial VEGF-A and ER-alpha expression, independently of plasma lipid level
      changes, but had no effect on MMP-3 and MMP-9 expression. CONCLUSIONS: These
      modulations of TIMPs, VEGF and ER-alpha expression induced by RSV may act as
      local stimulating factors for arteriolar growth in the myocardium.

PMID- 24854112
TI  - A multifunctional anomeric linker for the chemoenzymatic synthesis of complex
      oligosaccharides.
AB  - A new anomeric linker has been developed that facilitates the purification of
      glycans prepared by chemoenzymatic approaches and can readily give compounds that
      are appropriately modified for microarray development or glycan derivatives with
      a free reducing end that are needed as standards for the development of
      analytical protocols. 

PMID- 24854113
TI  - A single slide multiplex assay for the evaluation of classical Hodgkin lymphoma.
AB  - Classical Hodgkin lymphoma can be diagnosed with confidence in the majority of
      cases, but there is a significant subset that remains a diagnostic challenge. The
      authors have investigated the utility of a novel hyperplexing technology,
      MultiOmyxTM, which may be applied to stain with >60 antibodies on single tissue
      sections from formalin-fixed paraffin-embedded tissue as an aid to the diagnosis
      of classical Hodgkin lymphoma. The multiplexing protocol included CD30, CD15, PAX
      5, CD20, CD79a, CD45, BOB.1, OCT-2, and CD3 antibodies. The technology showed a
      high degree of sensitivity, specificity, and precision. Comparison studies with
      routine hematoxylin and eosin and immunohistochemical assessment of
      hematopathology cases in which classical Hodgkin lymphoma was included in the
      differential diagnosis showed concordance in 54 of 56 cases, with the 2
      discordant cases illustrating the potential of this multiplexed
      immunofluorescence technology to improve on traditional immunohistochemistry for
      classical Hodgkin lymphoma diagnosis. This technology is practical for routine
      diagnosis and may be particularly useful in cases in which the sample size is
      limited, few Hodgkin-like cells are present, or in CD30-positive lymphoma cases
      with difficult morphology. MultiOmyx may potentially benefit other areas of
      research and diagnostic pathology. 

PMID- 24854116
TI  - Bilateral transversus abdominus plane (TAP) blocks and their role in facilitating
      extubation in a patient with intracranial hypertension.

PMID- 24854117
TI  - [Learn, listen, think and commit in order to create and serve].

PMID- 24854114
TI  - Meibomian gland loss due to trabeculectomy.
AB  - PURPOSE: To evaluate meibomian gland loss after trabeculectomy with mitomycin C
      (MMC). METHODS: This cross-sectional observational case study involved 55 eyes in
      39 patients who had undergone trabeculectomy with MMC administered to the upper
      area of the eye. We used a mobile pen-shaped noncontact meibography system to
      access the morphology and determine loss of the meibomian glands. Meibomian gland
      loss was scored (meiboscore) from grade 0 (no loss of the meibomian glands)
      through grade 3 (loss of more than two-thirds of the total area) in the bleb
      contacting and bleb-noncontacting upper eyelid areas in the primary position and
      in the lower eyelid. The tear film breakup time (BUT) was also measured. RESULTS:
      The median duration from trabeculectomy to examination was 7.4 years
      (interquartile range 3.1-14.2). The meiboscores of the bleb-contacting upper
      eyelid areas were significantly higher than those for the bleb-noncontacting
      upper eyelid areas (P < 0.001). The meiboscores for both the bleb-contacting and
      the bleb-noncontacting upper eyelid areas were significantly higher when the bleb
      was avascular (P = 0.011 and P = 0.008, respectively). The meiboscores of the
      bleb-contacting and bleb-noncontacting upper eyelid areas showed a significant
      negative correlation with the BUT (r = -0.330, P = 0.014 and r = -0.296, P =
      0.028, respectively). CONCLUSION: Blebs that occur after trabeculectomy with MMC
      may be the cause of meibomian gland loss, particularly when the bleb is
      avascular. The presence of an avascular bleb warrants extra vigilance for
      decreased meibomian gland secretions because this decrease can lead to tear
      dysfunction and ocular surface damage, including bleb-wall damage.

PMID- 24854118
TI  - Hypothermia did not prevent epilepsy following experimental status epilepticus.
AB  - In epilepsy research, one of the major challenges is to prevent or at least
      mitigate development of epilepsy following acquired brain insult by early
      therapeutic interventions. So far, all pharmacological antiepileptogenic
      treatment approaches were largely unsuccessful in clinical trials and in
      experimental animal studies. In a well-established rat model of chronic epilepsy
      following self-sustaining status epilepticus (SSSE), we assessed the
      antiepileptogenic properties of 3-h-cooling induced directly after the end of
      SSSE. Occurrence of spontaneous seizures and seizure severity up to 8 weeks after
      SSSE were compared with normothermic SSSE controls. Furthermore,
      electrophysiological parameters assessing inhibition and excitation in the
      dentate gyrus were assessed at multiple time points. Post SSSE hypothermia did
      not prevent the occurrence of seizures in any animal. Eight weeks after SSSE,
      Racine motor seizures trended to be less severe following cooling (4.0+/-0.6)
      compared with normothermic controls (4.8+/-0.2) but the difference was not
      significant when testing for multiple comparisons. Early loss of inhibition that
      is typically seen following SSSE was somewhat attenuated in cooled animals 3h
      after SSSE as expressed by smaller paired-pulse ratios (PPR; 0.16+/-0.21)
      compared with normothermic controls (0.54+/-0.21) but difference was not
      significant either. Latency between stimulus artefact and excitatory post
      synaptic potential 3h after SSSE, reciprocally reflecting neuronal excitation,
      was higher in animals that underwent hypothermia (8.29+/-2.45 ms) compared with
      controls (4.82+/-0.66 ms), difference was not significant after correction for
      multiple comparisons. In summary, the current experiments were not able to
      demonstrate prevention or mitigation of epileptogenesis with immediate short-term
      cooling following SSSE.

PMID- 24854119
TI  - Abnormal intracellular calcium homeostasis associated with vulnerability in the
      nerve cells from heroin-dependent rat.
AB  - The cellular mechanisms by which opiate addiction develops with repetitive use
      remain largely unresolved. Intercellular calcium homeostasis is one of the most
      critical elements to determine neuroadaptive changes and neuronal fate. Heroin,
      one of the most addictive opiates, may induce neurotoxicity potentially inducing
      brain impairment, especially for those chronic users who get an overdose. Here we
      examined changes in intracellular calcium concentration ([Ca2+]i) after repeated
      exposure to heroin using cultured cerebral cortical neurons. Dynamic changes in
      [Ca2+]i indicated by fluo-3-AM were monitored using confocal laser scan
      microscopy, followed by cytotoxicity assessments. It showed that the cells
      dissociated from heroin-dependent rats had a smaller depolarization-induced
      [Ca2+]i responses, and a higher elevation in [Ca2+]i when challenged with a high
      concentration of heroin (500 MUM). The restoration ability to remove calcium
      after washout of these stimulants was impaired. Calcium channel blocker verapamil
      inhibited the heroin-induced [Ca2+]i elevations as well as the heroin-induced
      cell damage. The relative [Ca2+]i of the nerve cells closely correlated with the
      number of damaged cells induced by heroin. These results demonstrate that nerve
      cells from heroin-dependent rats manifest abnormal [Ca2+]i homeostasis, as well
      as vulnerability to heroin overdose, suggesting involvement of [Ca2+]i regulation
      mechanisms in heroin addiction and neurotoxicity.

PMID- 24854120
TI  - The structure and function of actin cytoskeleton in mature glutamatergic
      dendritic spines.
AB  - Dendritic spines are actin-rich protrusions from the dendritic shaft, considered
      to be the locus where most synapses occur, as they receive the vast majority of
      excitatory connections in the central nervous system (CNS). Interestingly,
      hippocampal spines are plastic structures that contain a dense array of molecules
      involved in postsynaptic signaling and synaptic plasticity. Since changes in
      spine shape and size are correlated with the strength of excitatory synapses,
      spine morphology directly reflects spine function. Therefore several
      neuropathologies are associated with defects in proteins located at the spines.
      The present work is focused on the spine actin cytoskeleton attending to its
      structure and function mainly in glutamatergic neurons. It addresses the study of
      the structural plasticity of dendritic spines associated with long-term
      potentiation (LTP) and the mechanisms that underlie learning and memory
      formation. We have integrated the current knowledge on synaptic proteins to
      relate this plethora of molecules with actin and actin-binding proteins. We
      further included recent findings that outline key uncharacterized proteins that
      would be useful to unveil the real ultrastructure and function of dendritic
      spines. Furthermore, this review is directed to understand how such spine
      diversity and interplay contributes to the regulation of spine morphogenesis and
      dynamics. It highlights their physiological relevance in the brain function, as
      well as it provides insights for pathological processes affecting dramatically
      dendritic spines, such as Alzheimer's disease. 

PMID- 24854121
TI  - Endophilin-1 regulates blood-brain barrier permeability by controlling ZO-1 and
      occludin expression via the EGFR-ERK1/2 pathway.
AB  - The blood-brain barrier (BBB) plays a pivotal role in maintenance and regulation
      of the neural microenvironment. Brain endothelial cells (BECs), held together by
      tight junctions (TJs), have a primary role in restricting the permeability of the
      BBB. Endophilin-1 is a multifunctional protein that influences epithelial growth
      factor receptor (EGFR) endocytosis and degradation and plays an important role in
      regulating the glomerular filtration barrier in the kidney. Endophilin-1 likely
      plays a similar role in controlling BBB permeability. In this study, we therefore
      analyzed the expression and function of endophilin-1 in the human BEC line
      hCMEC/D3. Our results show that endophilin-1 over-expression reduced the
      expression of the TJ-associated proteins ZO-1 and occludin and increased the
      paracellular permeability of hCMEC/D3 cells, whereas silencing of endogenous
      endophilin-1 yielded the opposite results. Over-expression of ZO-1 and occludin
      prevented the increase in permeability induced by endophilin-1 over-expression,
      whereas down-regulation of ZO-1 and occludin prevented the reduction in
      permeability induced by endophilin-1 silencing. Co-localization and co
      immunoprecipitation experiments suggested that endophilin-1 interacts with the
      EGFR. The levels of EGFR and its downstream effector phosphorylated extracellular
      signal-regulated kinase 1/2 (p-ERK1/2) are significantly decreased when
      endophilin-1 is over-expressed. Conversely, endophilin-1 down-regulation led to
      markedly increased levels of these proteins. In addition, the reduced
      permeability induced by endophilin-1 down-regulation was blocked by AG1478 and
      PD98059, inhibitors of EGFR and ERK1/2, respectively. Up-regulation of ZO-1 and
      occludin was blocked by the EGFR and ERK1/2 inhibitors. These results suggest
      that endophilin-1 regulates BBB permeability by controlling ZO-1 and occludin
      expression via the EGFR-ERK1/2 pathway in BECs. 

PMID- 24854122
TI  - 3-Methyl-1-phenyl-2-pyrazolin-5-one or N-acetylcysteine prevents hippocampal
      mossy fiber sprouting and rectifies subsequent convulsive susceptibility in a rat
      model of kainic acid-induced seizure ceased by pentobarbital.
AB  - There is accumulating evidence that reactive oxygen species are involved in the
      development of seizures under pathological conditions, and antioxidant treatments
      are a novel therapeutic approach for epilepsy. The kainic acid (KA) model of
      induced seizures has been widely used to study temporal lobe epilepsy. However,
      research on the use of free radical scavengers following KA-induced status
      epilepticus (SE) is limited. We examined whether antioxidants already used in
      humans could reduce hippocampal neuronal cell loss, mossy fiber sprouting and the
      acquisition of hyperexcitability when administered as a single dose after SE. The
      antioxidant 3-methyl-1-phenyl-2-pyrazolin-5-one (edaravone) (30mg/kg) or N
      acetylcysteine (NAC) (30mg/kg) was administered after KA-induced SE ceased by
      pentobarbital. We evaluated neuronal cell viability 1 week after SE, determined
      the threshold for seizures induced by inhalation of flurothyl ether 12 weeks
      after SE, and examined the extent of mossy fiber sprouting 12 weeks after SE. We
      found that edaravone or NAC prevented neuronal cell loss and mossy fiber
      sprouting, and increased the threshold for seizures induced by flurothyl ether,
      even when administered after KA-induced SE. These results demonstrate that a
      single dose of edaravone or NAC can protect against neuronal cell loss and
      epileptogenesis when administered after SE ceased by pentobarbital. 

PMID- 24854124
TI  - Angiotensin-(1-7) improves cognitive function in rats with chronic cerebral
      hypoperfusion.
AB  - Chronic cerebral hypoperfusion (CCH) is associated with cognitive decline in
      aging, vascular dementia and Alzheimer's disease. Recently, angiotensin-(1-7)
      (Ang-(1-7)), one of the physiological constituents of the brain, was found to
      protect against cognitive dysfunction and brain ischemia. However, the effects of
      Ang-(1-7) on CCH-induced cognitive deficits remained unknown. In the present
      study, Ang-(1-7) significantly alleviated CCH-induced cognitive deficits in rats
      subjected to permanent bilateral occlusion of the common carotid arteries (a
      model of CCH). This neuroprotective effect was associated with increased nitric
      oxide generation, attenuated neuronal loss and suppressed astrocyte proliferation
      in the hippocampus. These findings demonstrate that Ang-(1-7) is a promising
      therapeutic agent for CCH-induced cognitive deficits. 

PMID- 24854130
TI  - Nodular Fasciitis of the Breast: A Case and Literature Review.
AB  - Nodular fasciitis is a benign fibroblastic proliferation in soft tissue that is
      most commonly found in the upper extremities, trunk, head, and neck region. Its
      occurrence in the breast has been rarely reported. The most characteristic
      features are the sudden appearance and rapid growth of a palpable lesion. Nodular
      fasciitis can clinically, radiologically, and histopathologically mimic a breast
      carcinoma. We present a case of nodular fasciitis of the breast and a review of
      the relevant literature.

PMID- 24854123
TI  - Electroacupuncture pretreatment inhibits NADPH oxidase-mediated oxidative stress
      in diabetic mice with cerebral ischemia.
AB  - We investigated the protective effect of electroacupuncture (EA) on cerebral
      ischemic injury in diabetic mice, and explored the role of NADPH oxidase-mediated
      oxidative stress. Male C57BL/6 mice were injected streptozotocin to induce
      diabetes. The mice were pretreated with EA at acupoint "Baihui" for 30 min. Two
      hours after the end of EA pretreatment, focal cerebral ischemia was induced
      following 24h reperfusion. The neurobehavioral scores and infarction volumes,
      malondialdehyde (MDA), reactive oxygen species (ROS), and activation of NADPH
      oxidase were determined in the presence or absence of the NADPH oxidase inhibitor
      apocynin or activator tetrabromocinnamic acid (TBCA). EA pretreatment reduced
      infarct size and improved neurological outcomes 24h after reperfusion in the
      diabetic mice. EA also decreased cerebral MDA and ROS levels compared with the
      control group, and inhibited the NADPH oxidase activation. The beneficial effects
      were abolished by TBCA while pretreatment with apocynin mimicked the
      neuroprotective and anti-oxidative effects of EA. Our results demonstrated that
      EA attenuated cerebral ischemic injury by inhibiting NAPDH oxidase-mediated
      oxidative damage in diabetic mice. These results suggest a novel mechanism of EA
      pretreatment-induced tolerance in diabetic cerebral ischemia.

PMID- 24854132
TI  - Fusion of Magnetic Resonance Imaging and Real-Time Elastography to Visualize
      Prostate Cancer: A Prospective Analysis using Whole Mount Sections after Radical
      Prostatectomy.
AB  - PURPOSE: To determine whether the fusion of multiparametric magnetic resonance
      imaging (MRI) with transrectal real-time elastography (RTE) improves the
      visualization of PCa lesions compared to MRI alone. MATERIALS AND METHODS: In a
      prospective setting, 45 patients with biopsy-proven PCa received prostate MRI
      prior to radical prostatectomy (RP). T2 and diffusion-weighted imaging (T2WI/DW
      MRI) and, if applicable, dynamic contrast-enhanced sequences (T2WI/DW/DCE-MRI)
      were used to perform MRI/RTE fusion. The probability of PCa on MRI was graded
      according to the PI-RADS score for 12 different prostate sectors per patient. MRI
      images were fused with RTE to stratify suspicious from non-suspicious sectors.
      Imaging results were compared to whole mount sections using nonparametrical
      receiver operating characteristic curves and the area under these curves (AUC).
      RESULTS: 41 of 45 patients were eligible for final analyses. Histopathology
      confirmed PCa in 261 (53%) of 492 prostate sectors. MRI alone provided an AUC of
      0.62 (T2WI/DW-MRI) and 0.65 (T2WI/DW/DCE-MRI) to predict PCa and was meaningfully
      enhanced to 0.75 (T2WI/DW-MRI) and 0.74 (T2WI/DW/DCE-MRI) using MRI/RTE fusion.
      Sole MRI showed a sensitivity and specificity of 57.9% and 61% with the best
      results for ventral prostate sectors whereas RTE was superior in dorsal and
      apical sectors. MRI/RTE fusion improved sensitivity and specificity to 65.9% and
      75.3%, respectively. Additional use of DCE sequences showed a sensitivity and
      specificity of 65% and 55.7% for MRI and 72.1% and 66% for MRI/RTE fusion.
      CONCLUSION: MRI/RTE fusion provides improved PCa visualization by combining the
      strength of both imaging techniques in regard to prostate zonal anatomy and
      thereby might improve future biopsy-guided PCa detection.

PMID- 24854131
TI  - Prenatal assessment of ventriculocoronary connections and ventricular endocardial
      fibroelastosis in hypoplastic left heart.
AB  - OBJECTIVE: The outlook for newborns with hypoplastic left heart (HLH) has
      substantially improved over the last decade. However, differences in outcome
      among various anatomical subgroups have been described. We aimed to describe the
      incidence of ventriculocoronary communications and endocardial fibroelastosis in
      HLH and the possible implication on hospital survival (30 d). METHODS: We
      retrospectively reviewed our medical records, still frames and video loops of 72
      fetuses with HLH and critical aortic valve stenosis and evolving HLH from 2008 -
      2013. The presence of VCAC and EFE were systematically assessed. Outcome
      parameters were incidence of VCAC and EFE among different anatomical subgroups of
      HLH and hospital survival (30 d). RESULTS: 72 fetuses were included in this
      series. The incidence of VCAC was 11.1 % (8 cases) and EFE occurred in 33.3 % (24
      cases). 5 fetuses with VCAC occurred in the subgroup of mitral valve
      stenosis/aortic valve atresia (MS/AA, 62.5 %) and 2 fetuses with VCAC occurred in
      the group of mitral atresia/aortic valve atresia (MA/AA, 25 %). Further
      classification was not possible in one case with VCAC (12.5 %). EFE predominantly
      occurred in the subgroup of MS/AA, MA/AA and in those cases with aortic valve
      stenosis and evolving HLH. The overall hospital survival on an intention-to-treat
      basis was 91.2 % (52/57 newborns). Hospital survival was 91 % for the subgroup of
      cases with MS/AA and for all other anatomical subgroups. CONCLUSION: The presence
      of VCAC in HLH can be diagnosed by fetal echocardiography predominantly occurring
      in cases with obstructed outflow and to some extent patent mitral valve. EFE is a
      frequent coexisting finding. Hospital survival was comparable among different
      anatomical subgroups and in cases with VCAC. The presence of VCAC in HLH did not
      limit the results of surgical palliation within the observation period of 30
      days.

PMID- 24854133
TI  - EUS-Guided Bile Duct Drainage (EUBD) in 95 Patients.
AB  - PURPOSE: Bile duct stenting during ERCP has long been established as the gold
      standard for the treatment of biliary obstruction. However, when the ampulla
      cannot be reached or bile duct cannulation fails, percutaneous or surgical
      drainage is performed. The study aimed to investigate the feasibility and long
      term outcome of a potential alternative intervention, EUS-guided transluminal
      biliary drainage (EUBD), in a representative number of patients. MATERIALS AND
      METHODS: All patients undergoing EUBD were included in a prospectively collected
      single-center database over a 10-year period. Feasibility was characterized by
      technical and clinical success, including long-term follow-up data. RESULTS: From
      IV/2002 - XI/2012, 10 832 EUS and 8756 ERCP procedures were performed.
      Simultaneously, 223 PTCD and 95 EUBD were performed. Cholangiography was achieved
      in 93/95 patients (97.9 %). However, in one patient stone extraction was executed
      by means of the rendezvous technique. Therefore, drainage was not necessary.
      Intention to treat with EUS-guided drainage was given in 80/94 patients (86.9 %)
      using different techniques depending on anatomical variations and requirements.
      The cause of bile duct obstruction could not be cured in 77 patients
      (malignancy). In 18 patients, a benign (n = 15) or unknown etiology (n = 3) of
      bile duct stenosis was found. The complication rate was 15.7 % (mortality, 1.1 %;
      n = 1/95). The follow-up ranged from 3 - 60 months with reintervention in 3
      patients. CONCLUSION: EUBD is a promising therapy for bile duct obstruction in
      patients predominantly with malignant diseases. Using EUBD, an excellent
      interventional approach is available for long-term internal drainage to prevent
      percutaneous drainage (PTCD). EUS-guided drainage is challenging and needs
      extraordinary interventional expertise, preferentially in tertiary
      gastroenterological and endoscopic centers.

PMID- 24854134
TI  - Hidden physics in molecular rovibrational spectrum.
AB  - An algebraic method for rotational energies (AMr) is proposed to unearth the
      rotational spectrum {EJ} and the rovibrational interaction energies
      epsilonupsilonJint that are hidden in the rovibrational energies EupsilonJ. The
      applications to the excited electronic state a3Sigmau+ of 7Li2 and the ground
      state X1Sigma+ of NaF molecules show that: (1) the rotational energies EJ of the
      lighter 7Li2 molecule have better accuracies than the widely used rigid rotor
      rotational energies epsilonJrr particularly for the lowest two rotational states,
      while the rigid rotor model produces satisfied rotational energies for the
      heavier NaF molecule and (2) the attractive rovibrational interaction energies
      epsilonupsilonJint stabilize a molecular rovibrational system.

PMID- 24854136
TI  - EAACI position paper: irritant-induced asthma.
AB  - The term irritant-induced (occupational) asthma (IIA) has been used to denote
      various clinical forms of asthma related to irritant exposure at work. The causal
      relationship between irritant exposure(s) and the development of asthma can be
      substantiated by the temporal association between the onset of asthma symptoms
      and a single or multiple high-level exposure(s) to irritants, whereas this
      relationship can only be inferred from epidemiological data for workers
      chronically exposed to moderate levels of irritants. Accordingly, the following
      clinical phenotypes should be distinguished within the wide spectrum of irritant
      related asthma: (i) definite IIA, that is acute-onset IIA characterized by the
      rapid onset of asthma within a few hours after a single exposure to very high
      levels of irritant substances; (ii) probable IIA, that is asthma that develops in
      workers with multiple symptomatic high-level exposures to irritants; and (iii)
      possible IIA, that is asthma occurring with a delayed-onset after chronic
      exposure to moderate levels of irritants. This document prepared by a panel of
      experts summarizes our current knowledge on the diagnostic approach,
      epidemiology, pathophysiology, and management of the various phenotypes of IIA. 

PMID- 24854135
TI  - Optimization of beta-cyclodextrin cross-linked polymer for monitoring of
      quercetin.
AB  - A novel method for the separation/analysis of quercetin was described, which was
      based on the investigation of the inclusion interactions of beta-cyclodextrin
      cross-linked polymer (beta-CDCP) with quercetin (Qu) and the adsorption behavior
      of Qu on beta-CDCP. The inclusion interaction of beta-CDCP with Qu was studied
      through FTIR, TGA and 13C NMR. Under the optimum conditions, the preconcentration
      factor of the proposed method was approximately 8.8, the beta-CDCP could be used
      repeatedly for 30 times and offered better recovery. The linear range, limit of
      detection (LOD) and the relative standard deviation (RSD) was found to be 0.10
      12.0 MUg mL(-1), 4.6 ng mL(-1) and 3.10% (n=3, c=2.0 MUg mL(-1)) respectively.
      This technique had been successfully applied to the determination of Qu in real
      samples.

PMID- 24854137
TI  - Additional precursor purification in isobaric mass tagging experiments by
      traveling wave ion mobility separation (TWIMS).
AB  - Despite the increasing popularity of data-independent acquisition workflows, data
      dependent acquisition (DDA) is still the prevalent method of LC-MS-based
      proteomics. DDA is the basis of isobaric mass tagging technique, a powerful MS2
      quantification strategy that allows coanalysis of up to 10 proteomics samples. A
      well-documented limitation of DDA, however, is precursor coselection, whereby a
      target peptide is coisolated with other ions for fragmentation. Here, we
      investigated if additional peptide purification by traveling wave ion mobility
      separation (TWIMS) can reduce precursor contamination using a mixture of
      Saccharomyces cerevisiae and HeLa proteomes. In accordance with previous reports
      on FAIMS-Orbitrap instruments, we find that TWIMS provides a remarkable
      improvement (on average 2.85 times) in the signal-to-noise ratio for sequence
      ions. We also report that TWIMS reduces reporter ions contamination by around one
      third (to 14-15% contamination) and even further (to 6-9%) when combined with a
      narrowed quadrupole isolation window. We discuss challenges associated with
      applying TWIMS purification to isobaric mass tagging experiments, including
      correlation between ion m/z and drift time, which means that coselected peptides
      are expected to have similar mobility. We also demonstrate that labeling results
      in peptides having more uniform m/z and drift time distributions than observed
      for unlabeled peptides. Data are available via ProteomeXchange with identifier
      PXD001047. 

PMID- 24854138
TI  - Factors associated with intimate partner violence against women in a mega city of
      South-Asia: multi-centre cross-sectional study.
AB  - OBJECTIVES. To assess the proportion of women subjected to intimate partner
      violence and the associated factors, and to identify the attitudes of women
      towards the use of violence by their husbands. DESIGN. Cross-sectional study.
      SETTING. Family practice clinics at a teaching hospital in Karachi, Pakistan.
      PARTICIPANTS. A total of 520 women aged between 16 and 60 years were
      consecutively approached to participate in the study and interviewed by trained
      data collectors. Overall, 401 completed questionnaires were available for
      analysis. Multivariate logistic regression analysis was used to identify the
      association of various factors of interest. RESULTS. In all, 35% of the women
      reported being physically abused by their husbands in the last 12 months.
      Multivariate analysis showed that experiences of violence were independently
      associated with women's illiteracy (adjusted odds ratio=5.9; 95% confidence
      interval, 1.8-19.6), husband's illiteracy (3.9; 1.4-10.7), smoking habit of
      husbands (3.3; 1.9-5.8), and substance use (3.1; 1.7-5.7). CONCLUSION. It is
      imperative that intimate partner violence be considered a major public health
      concern. It can be prevented through comprehensive, multifaceted, and integrated
      approaches. The role of education is greatly emphasised in changing the
      perspectives of individuals and societies against intimate partner violence. 

PMID- 24854139
TI  - Current status of robot-assisted surgery.
AB  - The introduction of robot-assisted surgery, and specifically the da Vinci
      Surgical System, is one of the biggest breakthroughs in surgery since the
      introduction of anaesthesia, and represents the most significant advancement in
      minimally invasive surgery of this decade. One of the first surgical uses of the
      robot was in orthopaedics, neurosurgery, and cardiac surgery. However, it was the
      use in urology, and particularly in prostate surgery, that led to its widespread
      popularity. Robotic surgery, is also widely used in other surgical specialties
      including general surgery, gynaecology, and head and neck surgery. In this
      article, we reviewed the current applications of robot-assisted surgery in
      different surgical specialties with an emphasis on urology. Clinical results as
      compared with traditional open and/or laparoscopic surgery and a glimpse into the
      future development of robotics were also discussed. A short introduction of the
      emerging areas of robotic surgery were also briefly reviewed. Despite the
      increasing popularity of robotic surgery, except in robot-assisted radical
      prostatectomy, there is no unequivocal evidence to show its superiority over
      traditional laparoscopic surgery in other surgical procedures. Further trials are
      eagerly awaited to ascertain the long-term results and potential benefits of
      robotic surgery. 

PMID- 24854141
TI  - Finding the missing link for big biomedical data.

PMID- 24854140
TI  - The potential of mesenchymal stem cell in prion research.
AB  - Scrapie and bovine spongiform encephalopathy are fatal neurodegenerative diseases
      caused by the accumulation of a misfolded protein (PrP(res)), the pathological
      form of the cellular prion protein (PrP(C)). For the last decades, prion research
      has greatly progressed, but many questions need to be solved about prion
      replication mechanisms, cell toxicity, differences in genetic susceptibility,
      species barrier or the nature of prion strains. These studies can be developed in
      murine models of transmissible spongiform encephalopathies, although development
      of cell models for prion replication and sample titration could reduce economic
      and timing costs and also serve for basic research and treatment testing. Some
      murine cell lines can replicate scrapie strains previously adapted in mice and
      very few show the toxic effects of prion accumulation. Brain cell primary
      cultures can be more accurate models but are difficult to develop in naturally
      susceptible species like humans or domestic ruminants. Stem cells can be
      differentiated into neuron-like cells and be infected by prions. However, the use
      of embryo stem cells causes ethical problems in humans. Mesenchymal stem cells
      (MSCs) can be isolated from many adult tissues, including bone marrow, adipose
      tissue or even peripheral blood. These cells differentiate into neuronal cells,
      express PrP(C) and can be infected by prions in vitro. In addition, in the last
      years, these cells are being used to develop therapies for many diseases,
      including neurodegenerative diseases. We review here the use of cell models in
      prion research with a special interest in the potential use of MSCs.

PMID- 24854143
TI  - Detection, distribution, and genetic diversity of Australian grapevine viroid in
      grapevines in India.
AB  - Australian grapevine viroid (AGVd) is a viroid specific to grapevine with the
      least records in the world till date. Here, we report for the first time the
      presence of AGVd in grapevines in Indian sub-continent. The overall infection
      rate of AGVd in major grapevine producing areas in India was 9.3 %, which is
      conspicuously higher than the other regions of the world except for Tunisia and
      Iran. To understand the AGVd diversity in India, the genetic divergence was
      examined based on the disparity in the cultivars and the locations. Nucleotide
      sequence analysis revealed the existence of five major AGVd variants in India
      besides other 44 minor variants implying the "quasi-species" nature. Further,
      sequence alignment of all the Indian AGVd variants along with Australian type
      species underscored the presence of eleven mutation points which are archetypal
      for Indian AGVd, irrespective of the region, and cultivar of grapevines. Plotting
      of Indian AGVd sequence variants against Australian type species unveiled that
      all these eleven mutations are distributed on upper and lower left terminal and
      pathogenicity regions of the molecule. Phylogenetic analysis divulged all the
      major Indian AGVd variants formed two distinct clusters, suggesting the two
      separate evolutionary lineages of AGVd in Indian viticulture. 

PMID- 24854142
TI  - Molecular characteristics of the complete genome of a J-subgroup avian leukosis
      virus strain isolated from Eurasian teal in China.
AB  - The J-subgroup avian leukosis virus (ALV-J) strain WB11098J was isolated from a
      wild Eurasian teal, and its proviral genomic sequences were determined. The
      complete proviral sequence of WB11098J was 7868 nt long. WB11098J was 95.3.9 %
      identical to the prototype strain HPRS-103, 94.2 % identical to the American
      strain ADOL-7501, 94.5-94.7 % identical to Chinese broiler isolates, 94.8-97.5 %
      identical to layer chicken isolates, and 94.4-95.0 % identical to Chinese local
      chicken isolates at the nucleotide level. Phylogenetic analysis showed that the
      WB11098J isolate shared the greatest homology with the layer strain SD09DP03 and
      was included in the same cluster. Interestingly, two 19-bp insertions in the U3
      regions of the 5'LTR and 5'UTR that were most likely derived from other
      retroviruses were found in the WB11098J isolate. These insertions separately
      introduced one E2BP-binding site in the U3 region of the 5'LTR and a RNA
      polymerase II transcription factor IIB and core promoter motif of ten elements in
      the 5'UTR. A 5-bp deletion was identified in the U3 region of the 5'LTR. No
      nucleotides were deleted in the rTM or DR-1 regions in the 3'UTR. A 1-bp deletion
      was detected in the E element and introduced a specific and distinct binding site
      for c-Ets-1. Our study is the first to report the molecular characteristics of
      the complete genome of an ALV-J that was isolated from a wild bird and will
      provide necessary information for further understanding of the evolution of ALV
      J. 

PMID- 24854145
TI  - Atorvastatin improves survival of implanted stem cells in a rat model of renal
      ischemia-reperfusion injury.
AB  - AIMS: To investigate the impacts of combinatorial atorvastatin (Ator)
      perioperative administration and mesenchymal stem cell (MSC) implantation on
      therapeutic effects in the rat experimental acute kidney injury. METHODS: The
      model of renal ischemia-reperfusion (I/R) injury was induced by the release of
      bilateral renal pedicle clamps following 45 min of occlusion. Immediately after
      reperfusion, CM-Dil-labeled MSCs (1 * 10(6) cells) or vehicles only were
      administered through the carotid artery of the animals pretreated with or without
      Ator. RESULTS: The combined treatment with Ator and MSCs (Ator+MSCs) markedly
      reduced the elevated levels of serum creatinine and blood urea nitrogen, as well
      as the severity of renal damage 24 h after I/R injury. In addition, we also
      observed inhibition of renal tubular cell apoptosis and promotion of
      proliferation in the Ator+MSCs group compared with the other groups. Consistent
      with the improvement in renal function and morphology, Ator pretreatment
      significantly ameliorated oxidative stress, inhibited inflammation response, and
      increased the viability of implanted MSCs. With regard to the further mechanism,
      we found that the expression of Toll-like receptor 4 (TLR4) and high-mobility
      group box 1, potential mediators of innate immunity, was significantly decreased
      in the Ator-treated groups. CONCLUSION: Ator treatment may protect the kidney
      undergoing I/R injury through suppression of TLR4 signaling, creating a better
      environment for the survival of grafted MSCs. The extra benefit of the Ator+MSCs
      combined therapy may result from the Ator-mediated inhibition of oxidative stress
      and inflammation in the ischemic kidney.

PMID- 24854146
TI  - Severe toxic leukoencephalopathy associated with tacrolimus after living donor
      liver transplantation.

PMID- 24854147
TI  - Uncommon and/or bizarre features of dementia.
AB  - This study aimed at describing uncommon or bizarre symptoms observed in patients
      suffering from dementia. Medline and Google scholar searches were conducted for
      relevant articles, chapters, and books published since 1967. Search terms used
      included uncommon presentation, behavioural and psychological symptoms, dementia,
      Alzheimer's disease, and fronto-temporal dementia. Publications found through
      this indexed search were reviewed for further relevant references. The uncommon
      symptoms are described as case-reports and there are no systematic
      investigations. Bizarre behaviours arising late in life should be thoroughly
      investigated as symptoms of dementia. 

PMID- 24854148
TI  - Surfactant-copper(II) Schiff base complexes: synthesis, structural investigation,
      DNA interaction, docking studies, and cytotoxic activity.
AB  - A series of surfactant-copper(II) Schiff base complexes (1-6) of the general
      formula, [Cu(sal-R2)2] and [Cu(5-OMe-sal-R2)2], {where, sal=salicylaldehyde, 5
      OMe-sal=5-methoxy- salicylaldehyde, and R2=dodecylamine (DA), tetradecylamine
      (TA), or cetylamine (CA)} have been synthesized and characterized by
      spectroscopic, ESI-MS, and elemental analysis methods. For a special reason, the
      structure of one of the complexes (2) was resolved by single crystal X-ray
      diffraction analysis and it indicates the presence of a distorted square-planar
      geometry in the complex. Analysis of the binding of these complexes with DNA has
      been carried out adapting UV-visible-, fluorescence-, as well as circular
      dichroism spectroscopic methods and viscosity experiments. The results indicate
      that the complexes bind via minor groove mode involving the hydrophobic
      surfactant chain. Increase in the length of the aliphatic chain of the ligands
      facilitates the binding. Further, molecular docking calculations have been
      performed to understand the nature as well as order of binding of these complexes
      with DNA. This docking analysis also suggested that the complexes interact with
      DNA through the alkyl chain present in the Schiff base ligands via the minor
      groove. In addition, the cytotoxic property of the surfactant-copper(II) Schiff
      base complexes have been studied against a breast cancer cell line. All six
      complexes reduced the visibility of the cells but complexes 2, 3, 5, and 6
      brought about this effect at fairly low concentrations. Analyzed further, but a
      small percentage of cells succumbed to necrosis. Of these complexes (6) proved to
      be the most efficient aptotoxic agent.

PMID- 24854144
TI  - Recombinant dengue 2 virus NS3 protein conserves structural antigenic and
      immunological properties relevant for dengue vaccine design.
AB  - The NS3 protein is a multifunctional non-structural protein of flaviviruses
      implicated in the polyprotein processing. The predominance of cytotoxic T cell
      lymphocytes epitopes on the NS3 protein suggests a protective role of this
      protein in limiting virus replication. In this work, we studied the antigenicity
      and immunogenicity of a recombinant NS3 protein of the Dengue virus 2. The full
      length NS3 gene was cloned and expressed as a His-tagged fusion protein in
      Escherichia coli. The pNS3 protein was purified by two chromatography steps. The
      recombinant NS3 protein was recognized by anti-protease NS3 polyclonal antibody
      and anti-DENV2 HMAF by Western Blot. This purified protein was able to stimulate
      the secretion of high levels of gamma interferon and low levels of interleukin-10
      and tumor necrosis factor-alpha in mice splenocytes, suggesting a predominantly
      Th-1-type T cell response. Immunized BALB/c mice with the purified NS3 protein
      showed a strong induction of anti-NS3 IgG antibodies, essentially IgG2b, as
      determined by ELISA. Immunized mice sera with recombinant NS3 protein showed
      specific recognition of native dengue protein by Western blotting and
      immunofluorescence techniques. The successfully purified recombinant protein was
      able to preserv the structural and antigenic determinants of the native dengue
      protein. The antigenicity shown by the recombinant NS3 protein suggests its
      possible inclusion into future DENV vaccine preparations. 

PMID- 24854150
TI  - Abstracts of the Annual Meeting of the Austrian Society of Cardiology, May 28-31,
      2014, Salzburg, Austria.

PMID- 24854149
TI  - The case for medical marijuana in epilepsy.
AB  - Charlotte, a little girl with SCN1A-confirmed Dravet syndrome, was recently
      featured in a special that aired on CNN. Through exhaustive personal research and
      assistance from a Colorado-based medical marijuana group (Realm of Caring),
      Charlotte's mother started adjunctive therapy with a high concentration
      cannabidiol/Delta(9) -tetrahydrocannabinol (CBD:THC) strain of cannabis, now
      known as Charlotte's Web. This extract, slowly titrated over weeks and given in
      conjunction with her existing antiepileptic drug regimen, reduced Charlotte's
      seizure frequency from nearly 50 convulsive seizures per day to now 2-3 nocturnal
      convulsions per month. This effect has persisted for the last 20 months, and
      Charlotte has been successfully weaned from her other antiepileptic drugs. We
      briefly review some of the history, preclinical and clinical data, and
      controversies surrounding the use of medical marijuana for the treatment of
      epilepsy, and make a case that the desire to isolate and treat with
      pharmaceutical grade compounds from cannabis (specifically CBD) may be inferior
      to therapy with whole plant extracts. Much more needs to be learned about the
      mechanisms of antiepileptic activity of the phytocannabinoids and other
      constituents of Cannabis sativa.

PMID- 24854151
TI  - Cross-finger dermal pocketing to augment venous outflow for distal fingertip
      replantation.
AB  - Venous anastomosis in distal fingertip replantations is not always possible, and
      venous congestion is recognized as a potential cause of failure. Methods
      previously described to address this problem include amputate deepithelization
      and dermal pocketing postarterial anastomosis to augment venous outflow. However,
      attachment of the digit to the palm or abdomen resulted in finger stiffness. We
      describe a modification of the previous methods by utilizing dermal flaps raised
      from the adjacent digit in the form of a cross-finger flap. The key differences
      are the partial deepithelization of the replanted fingertip and subsequent
      replacement of the dermal flap to the donor digit to minimize donor site
      morbidity. During the period where the 2 digits are attached, interphalangeal
      joint mobilization is permitted to maintain joint mobility. 

PMID- 24854152
TI  - Latissimus dorsi tendon transfer for massive, irreparable posterosuperior rotator
      cuff tears: surgical technique.
AB  - Massive rotator cuff tears remain a complex and challenging problem for both the
      patient and the surgeon. Although significant advancements in surgical techniques
      as well as technology for arthroscopic and mini-open rotator cuff repairs have
      been made, many massive tears result in failed repair with continued progressive
      tendon retraction and degeneration. In cases when primary tendon to bone healing
      is impractical, latissimus dorsi tendon transfer provides promising and
      reproducible clinical results. Herein, we present a latissimus tendon transfer
      surgical technique, a procedure we have used as a salvage operation for failed
      arthroscopic/mini-open primary rotator cuff repair. 

PMID- 24854154
TI  - Prevalence and risk factors of low bone mineral density in juvenile onset
      ankylosing spondylitis.
AB  - The objective of this study is to assess the prevalence and risk in patients with
      juvenile onset ankylosing spondylitis (JoAS) complicated with low bone mineral
      density (BMD). A total of 112 children and adolescents with JoAS were enrolled in
      the study. Bone mass was measured from the lumbar spine and the left proximal
      femur using dual-energy X-ray absorptiometry. According to the 2007 International
      Society of Clinical Densitometry definitions, a Z score of less than -2 was
      termed as "low BMD." Stepwise regression analysis was used to investigate
      associations between low BMD and disease-related factors including gender, age,
      weight, height, body mass index, disease duration, HLA-B27 antigen, grades of
      sacroiliitis, Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index
      (BASFI), patient global assessment (PGA), spine pain, erythrocyte sedimentation
      rate (ESR), and C-reactive protein (CRP). Low BMD was found in 18 (16.1 %) cases
      in at least one of the two measured regions. Lumbar spine BMD had negative
      correlations with BASDAI, BASFI, spine pain, ESR, and CRP (P < 0.05). Hip BMD
      significantly negatively correlated with BASDAI and PGA (P < 0.05). In
      conclusion, patients with JoAS are likely to develop low BMD, which may be
      related to high disease activity. 

PMID- 24854153
TI  - Depression screening among older adults attending low-vision rehabilitation and
      eye-care services: Characteristics of those who screen positive and client
      acceptability of screening.
AB  - AIM: To investigate characteristics associated with screening positive for
      depressive symptoms among older adults accessing low-vision rehabilitation and
      eye-care services and to determine client acceptability of depression screening
      using the Patient Health Questionnaire-2 (PHQ-2) in these settings. METHODS: One
      hundred and twenty-four older adults (mean = 77.02 years, SD = 9.12) attending
      low-vision rehabilitation and eye-care services across Australia were screened
      for depression and invited to complete a telephone-administered questionnaire to
      determine characteristics associated with depressive symptoms and client
      acceptability of screening in these settings. RESULTS: Thirty-seven per cent (n =
      46/124) of participants screened positive for depressive symptoms, and the
      majority considered the new depression screening method to be a 'good idea' in
      vision services (85%). Severe vision loss (<6/60 in the better eye) was
      associated with an increased odds of screening positive for depressive symptoms
      (odds ratio 2.37; 95% confidence interval 1.08-6.70) even after adjusting for
      potential confounders. Participants who screened positive had a preference for
      'talking' therapy or a combination of medication and 'talking therapy' delivered
      within their own home (73%) or via telephone (67%). CONCLUSION: The PHQ-2 appears
      to be an acceptable method for depression screening in eye-care settings among
      older adults. Targeted interventions that incorporate home-based or telephone
      delivered therapy sessions may improve outcomes for depression in this group.

PMID- 24854156
TI  - Development of a watershed-based geospatial groundwater specific vulnerability
      assessment tool.
AB  - This study assesses and characterizes the vulnerability of unregulated
      groundwater systems to microbial contamination in 18 counties in the state of
      Georgia using a contamination risk screening strategy based on watershed
      characteristics and elements of the Safe Drinking Water Act's Wellhead Protection
      program. Environmental data sources analyzed include septic systems, elevation,
      land use and land cover data, soil, vegetation coverage, demographics, and
      livestock. A geospatial overlay/index modeling approach was developed to identify
      areas of higher vulnerability for groundwater pollution by taking into
      consideration watershed land use, hydrology, and topography (LHT). Sensitivity
      analysis was used to evaluate the effectiveness of model variables. The results
      of the model were validated by using field data and output from U.S. EPA's
      DRASTIC model, a widely used intrinsic vulnerability assessment tool. The
      validation showed a higher risk of microbial contamination for wells located in a
      high to medium LHT vulnerability zones. LHT provided a clear distribution of
      satisfactory and unsatisfactory wells in the three vulnerability zones; however,
      the majority of wells (>75%), with both satisfactory and unsatisfactory test
      results, are located in medium DRASTIC vulnerability zone. This difference
      between LHT and DRASTIC can be attributed to the microbial contamination specific
      factors incorporated into LHT index. It is concluded that although inclusion of
      potential contamination sources on adjacent land uses in the vulnerability
      assessment framework adds to the complexity of the processes involved in a
      vulnerability assessment, such inclusion provides a meaningful perspective to
      groundwater protection efforts as an effective screening tool. 

PMID- 24854155
TI  - The ratio of anterior and posterior vertebral heights reinforces the utility of
      DXA in assessment of vertebrae strength.
AB  - The objective of the study was to introduce a new parameter describing bone
      strength with greater precision than the widely used antero-posterior DXA (dual
      energy X-ray absorptiometry), which measures areal bone mineral density (aBMD).
      The adjusted areal bone mineral density (AaBMD) defined as the ratio between aBMD
      and h a/h p (h a and h p: anterior and posterior vertebral body heights measured
      on the lateral view, respectively) is proposed: AaBMD = aBMD/(h a/h p). The
      utility of AaBMD in prediction of bone strength was assessed by in vitro
      measurements of cadaver L3 vertebrae. The AaBMD of 31 vertebrae was correlated
      with the ultimate stress (P max) and load (F max) values obtained in mechanical
      tests. The correlations were compared to those obtained for aBMD and for
      volumetric bone mineral density (vBMD) measured by computed tomography. The
      correlation of AaBMD to F max adjusted for donor's age was significantly higher
      than for aBMD and vBMD (r = 0.740, 0.658, and 0.609, respectively, p < 0.05). The
      differences between partial correlation coefficients for P max to AaBMD, aBMD and
      vBMD relationships were smaller (r = 0.764, 0.720, and 0.732, respectively, p <
      0.05), but also showed the superiority of AaBMD. Combining antero-posterior DXA
      aBMD and the lateral h a/h p ratio, measured, for example, by the Vertebral
      Fracture Assessment software of the new generation of DXA devices, seems to
      accurately predict the mechanical vertebral parameters related to bone strength.
      It is assumed that the proposed AaBMD parameter may be more predictive for
      fracture risk assessment, which requires further studies. 

PMID- 24854158
TI  - The lung allocation score goes global.

PMID- 24854157
TI  - Plasma profile of pro-inflammatory cytokines and chemokines in cocaine users
      under outpatient treatment: influence of cocaine symptom severity and psychiatric
      co-morbidity.
AB  - The treatment for cocaine use constitutes a clinical challenge because of the
      lack of appropriate therapies and the high rate of relapse. Recent evidence
      indicates that the immune system might be involved in the pathogenesis of cocaine
      addiction and its co-morbid psychiatric disorders. This work examined the plasma
      pro-inflammatory cytokine and chemokine profile in abstinent cocaine users (n =
      82) who sought outpatient cocaine treatment and age/sex/body mass-matched
      controls (n = 65). Participants were assessed with the diagnostic interview
      Psychiatric Research Interview for Substance and Mental Diseases according to the
      Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text
      Revision (DSM-IV-TR). Tumor necrosis factor-alpha, chemokine (C-C motif) ligand
      2/monocyte chemotactic protein-1 and chemokine (C-X-C motif) ligand 12
      (CXCL12)/stromal cell-derived factor-1 (SDF-1) were decreased in cocaine users,
      although all cytokines were identified as predictors of a lifetime pathological
      use of cocaine. Interleukin-1 beta (IL-1beta), chemokine (C-X3-C motif) ligand 1
      (CX3CL1)/fractalkine and CXCL12/SDF-1 positively correlated with the cocaine
      symptom severity when using the DSM-IV-TR criteria for cocaine abuse/dependence.
      These cytokines allowed the categorization of the outpatients into subgroups
      according to severity, identifying a subgroup of severe cocaine users (9-11
      criteria) with increased prevalence of co-morbid psychiatric disorders [mood
      (54%), anxiety (32%), psychotic (30%) and personality (60%) disorders]. IL-1beta
      was observed to be increased in users with such psychiatric disorders relative to
      those users with no diagnosis. In addition to these clinical data, studies in
      mice demonstrated that plasma IL-1beta, CX3CL1 and CXCL12 were also affected
      after acute and chronic cocaine administration, providing a preclinical model for
      further research. In conclusion, cocaine exposure modifies the circulating levels
      of pro-inflammatory mediators. Plasma cytokine/chemokine monitoring could improve
      the stratification of cocaine consumers seeking treatment and thus facilitate the
      application of appropriate interventions, including management of heightened risk
      of psychiatric co-morbidity. Further research is necessary to elucidate the role
      of the immune system in the etiology of cocaine addiction.

PMID- 24854159
TI  - Factors predictive of subsequent injury in a longitudinal cohort study.
AB  - OBJECTIVES: The aims are to: (1) Determine the cumulative incidence of self
      reported subsequent injury (of any anatomical site or injury type) occurring
      between 3 months and 12 months after a sentinel injury among participants in the
      Prospective Outcomes of Injury Study in New Zealand and (2) Examine the preinjury
      and injury-related predictors of subsequent injury. METHODS: Prospective Outcomes
      of Injury Study participants (n=2282) were interviewed 3 months, 5 months and 12
      months after a sentinel injury event. Data were collected about a range of
      preinjury and injury-related factors at the 3-month interview and about
      subsequent injury at the 5-month and 12-month interviews. Poisson regression
      modelling was used to determine the preinjury and injury-related predictors of
      subsequent injury. RESULTS: Between the 3-month and 12 month interviews 28% of
      the participants reported at least one subsequent injury. Subsequent injury was
      34% more likely among participants with a prior injury affecting them at the time
      of the sentinel injury compared with participants without a prior injury
      affecting them, and more likely among non-workers (31% more likely) and
      trade/manual workers (32% more likely) compared with professionals. Participants
      whose sentinel injury was due to assault were 43% more likely to report a
      subsequent injury compared with those whose sentinel injury was accidental. A
      subsequent injury was 23% less likely if the sentinel injury was a lower
      extremity fracture compared with other injuries, and 21% less likely if the
      sentinel injury event involved hospitalisation. CONCLUSIONS: Among general injury
      populations it may be possible to identify people at increased risk for
      subsequent injury.

PMID- 24854160
TI  - Regulation of the development of asthmatic inflammation by in situ CD4(+)Foxp3
      (+) T cells in a mouse model of late allergic asthma.
AB  - CD4(+)Foxp3(+)T cells (Tregs) mediate homeostatic peripheral tolerance by
      suppressing helper T2 cells in allergy. However, the regulation of asthmatic
      inflammation by local (in situ) Tregs in asthma remains unclear. BALB/c mice
      sensitized and challenged with ovalbumin (OVA) (asthma group) developed asthmatic
      inflammation with eosinophils and lymphocytes, but not mast cells. The number of
      Tregs in the circulation, pulmonary lymph nodes (pLNs), and thymi significantly
      decreased in the asthma group compared to the control group without OVA
      sensitization and challenge in the effector phase. The development of asthmatic
      inflammation is inversely related to decreased Tregs with reduced mRNA expression
      such as interleukin (IL)-4, transforming growth factor-beta1, and IL-10, but not
      interferon-gamma, in pLNs. Moreover, M2 macrophages increased in the local site.
      The present study suggests that Tregs, at least in part, may regulate the
      development of asthmatic inflammation by cell-cell contact and regional cytokine
      productions. 

PMID- 24854161
TI  - sHLA-G involved in the apoptosis of decidual natural killer cells following
      Toxoplasma gondii infection.
AB  - This study aims to assess whether soluble HLA-G (sHLA-G) is involved in apoptosis
      of decidual natural killer (dNK) cells following Toxoplasma gondii infection. dNK
      cells or NK-92 cells were infected with T. gondii and co-cultured with
      trophoblast cells or BeWo cells. Infected co-cultured cells were treated without
      or with sHLA-G neutralizing antibody. Uninfected co-cultured cells were used as
      controls. Apoptosis of dNK cells were analyzed by flow cytometry and confocal
      microscope. Real-time PCR and Western blot were used to determine caspase 3 and
      caspase 8 expression. sHLA-G in supernatant were measured by enzyme-linked
      immunosorbent assay (ELISA). In infection groups, sHLA-G was increased, while dNK
      apoptosis proteins caspase 3 and caspase 8 were up-regulated, but significantly
      decreased in the presence of sHLA-G neutralizing antibody compared to controls.
      Under the situation of T. gondii-infected dNK cells co-cultured with trophoblast
      cells, the up-regulation of sHLA-G could induce dNK cells apoptosis which
      ultimately may contribute to the abnormal pregnancy outcomes with T. gondii
      infection. 

PMID- 24854162
TI  - Pentraxin 3 inhibits acute renal injury-induced interstitial fibrosis through
      suppression of IL-6/Stat3 pathway.
AB  - Acute kidney injury-induced organ fibrosis is recognized as a major risk factor
      for the development of chronic kidney disease, which remains one of the leading
      causes of death in the developed world. However, knowledge on molecules that may
      suppress the fibrogenic response after injury is lacking. The long pentraxin 3
      (PTX3), a novel acute renal injury marker, has been reported to be involved in
      chronic renal injury, but the mechanism is still unknown. In this experiment, the
      mice subjected to acute kidney injury showed a slow recovery of kidney function
      compared with PTX3-treated animals. Collagen expression was absent in sham
      operated kidneys; however, their expression was significantly increased after
      reperfusion. And, these changes were reduced in PTX3-treated mouse kidney.
      Fibrosis was associated with increased expression of IL-6 and extensive
      activation of Stat3. Administration of IL-6 increased collagen I expression and
      Stat3 activation in vitro in renal epithelial cells subjected to hypoxia
      reoxygenation, which was suppressed by PTX3. Furthermore, we found that the
      decreased serum creatinine level and the reduced expression of collagen and
      smooth muscle actin induced by PTX3 were abolished by additional administration
      of IL-6. The associated p-Stat3 expression which was reduced by PTX3
      administration was also inverted by additional IL-6 treatment. Our data suggest
      that PTX3 inhibits acute renal injury-induced interstitial fibrosis through
      suppression of IL-6/Stat3 pathway. 

PMID- 24854163
TI  - Wogonoside ameliorates lipopolysaccharide-induced acute lung injury in mice.
AB  - Wogonoside has been reported to have anti-inflammatory properties. In this study,
      we evaluated the effect of wogonoside on lipopolysaccharide (LPS)-induced acute
      lung injury (ALI) in mice. Male BALB/c mice with ALI, induced by intranasal
      instillation of LPS, were treated with wogonoside 1 h prior to LPS exposure. Mice
      treated with LPS alone showed significantly increased TNF-alpha, IL-6, and IL
      1beta levels in the bronchoalveolar lavage fluid (BALF). When pretreated with
      wogonoside, the TNF-alpha, IL-6, and IL-1beta levels were significantly
      decreased. Meanwhile, wogonoside significantly inhibited LPS-induced increases in
      the macrophage and neutrophil infiltration of lung tissues and markedly
      attenuated myeloperoxidase activity. Furthermore, wogonoside inhibited the TLR4
      expression and the phosphorylation of NF-kappaB p65, and IkappaB induced by LPS.
      In conclusion, our results indicate that wogonoside exhibits a protective effect
      on LPS-induced ALI via suppression of TLR4-mediated NF-kappaB signaling pathways.

PMID- 24854164
TI  - Panic attacks and hoarding disorder: an initial investigation.
AB  - Panic attacks (PAs) defined as a discrete period of intense fear or discomfort,
      occur in the context of numerous anxiety and mood related disorders. Research has
      suggested that PAs serve as a significant indicator and prognostic factor for
      overall symptom severity, course, and comorbidity within various conditions.
      Consequently, a PA specifier is now applicable to all DSM-5 disorders. Despite
      these clinical and nosological implications, no research to date has examined
      associations between PAs and hoarding disorder. The current investigation
      evaluated relationships between PA endorsement and hoarding severity within a
      sample of 32 patients with hoarding disorder. Findings suggested a high rate of
      panic history among those with hoarding disorder (56%). Hoarders with co
      occurring PAs, compared to those without PAs, evidenced significantly higher
      symptom severity. Moreover, PAs continued to significantly predict hoarding
      severity even after controlling for relevant covariates. When examining the
      specific relationships among PAs and hoarding symptoms (i.e., acquiring,
      difficulty discarding, and clutter), the endorsement of PAs was associated with
      increased acquiring and difficulty discarding symptoms. These findings add
      considerably to a growing body of literature on hoarding disorder. Implications
      for the assessment and treatment of PAs that co-occur with hoarding disorder are
      discussed. 

PMID- 24854166
TI  - Essential plasticity and redundancy of metabolism unveiled by synthetic lethality
      analysis.
AB  - We unravel how functional plasticity and redundancy are essential mechanisms
      underlying the ability to survive of metabolic networks. We perform an exhaustive
      computational screening of synthetic lethal reaction pairs in Escherichia coli in
      a minimal medium and we find that synthetic lethal pairs divide in two different
      groups depending on whether the synthetic lethal interaction works as a backup or
      as a parallel use mechanism, the first corresponding to essential plasticity and
      the second to essential redundancy. In E. coli, the analysis of pathways
      entanglement through essential redundancy supports the view that synthetic
      lethality affects preferentially a single function or pathway. In contrast,
      essential plasticity, the dominant class, tends to be inter-pathway but strongly
      localized and unveils Cell Envelope Biosynthesis as an essential backup for
      Membrane Lipid Metabolism. When comparing E. coli and Mycoplasma pneumoniae, we
      find that the metabolic networks of the two organisms exhibit a large difference
      in the relative importance of plasticity and redundancy which is consistent with
      the conjecture that plasticity is a sophisticated mechanism that requires a
      complex organization. Finally, coessential reaction pairs are explored in
      different environmental conditions to uncover the interplay between the two
      mechanisms. We find that synthetic lethal interactions and their classification
      in plasticity and redundancy are basically insensitive to medium composition, and
      are highly conserved even when the environment is enriched with nonessential
      compounds or overconstrained to decrease maximum biomass formation. 

PMID- 24854165
TI  - CD8+ T cells from a novel T cell receptor transgenic mouse induce liver-stage
      immunity that can be boosted by blood-stage infection in rodent malaria.
AB  - To follow the fate of CD8+ T cells responsive to Plasmodium berghei ANKA (PbA)
      infection, we generated an MHC I-restricted TCR transgenic mouse line against
      this pathogen. T cells from this line, termed PbT-I T cells, were able to respond
      to blood-stage infection by PbA and two other rodent malaria species, P. yoelii
      XNL and P. chabaudi AS. These PbT-I T cells were also able to respond to
      sporozoites and to protect mice from liver-stage infection. Examination of the
      requirements for priming after intravenous administration of irradiated
      sporozoites, an effective vaccination approach, showed that the spleen rather
      than the liver was the main site of priming and that responses depended on
      CD8alpha+ dendritic cells. Importantly, sequential exposure to irradiated
      sporozoites followed two days later by blood-stage infection led to augmented PbT
      I T cell expansion. These findings indicate that PbT-I T cells are a highly
      versatile tool for studying multiple stages and species of rodent malaria and
      suggest that cross-stage reactive CD8+ T cells may be utilized in liver-stage
      vaccine design to enable boosting by blood-stage infections. 

PMID- 24854167
TI  - Host responses and metabolic profiles of wood components in Dutch elm hybrids
      with a contrasting tolerance to Dutch elm disease.
AB  - BACKGROUND AND AIMS: Changes occurring in the macromolecular traits of cell wall
      components in elm wood following attack by Ophiostoma novo-ulmi, the causative
      agent of Dutch elm disease (DED), are poorly understood. The purpose of this
      study was to compare host responses and the metabolic profiles of wood components
      for two Dutch elm (Ulmus) hybrids, 'Groeneveld' (a susceptible clone) and
      'Dodoens' (a tolerant clone), that have contrasting survival strategies upon
      infection with the current prevalent strain of DED. METHODS: Ten-year-old plants
      of the hybrid elms were inoculated with O. novo-ulmi ssp. americana * novo-ulmi.
      Measurements were made of the content of main cell wall components and
      extractives, lignin monomer composition, macromolecular traits of cellulose and
      neutral saccharide composition. KEY RESULTS: Upon infection, medium molecular
      weight macromolecules of cellulose were degraded in both the susceptible and
      tolerant elm hybrids, resulting in the occurrence of secondary cell wall ruptures
      and cracks in the vessels, but rarely in the fibres. The (13)C nuclear magnetic
      resonance spectra revealed that loss of crystalline and non-crystalline cellulose
      regions occurred in parallel. The rate of cellulose degradation was influenced by
      the syringyl:guaiacyl ratio in lignin. Both hybrids commonly responded to the
      medium molecular weight cellulose degradation with the biosynthesis of high
      molecular weight macromolecules of cellulose, resulting in a significant increase
      in values for the degree of polymerization and polydispersity. Other responses of
      the hybrids included an increase in lignin content, a decrease in relative
      proportions of d-glucose, and an increase in proportions of d-xylose.
      Differential responses between the hybrids were found in the syringyl:guaiacyl
      ratio in lignin. CONCLUSIONS: In susceptible 'Groeneveld' plants, syringyl-rich
      lignin provided a far greater degree of protection from cellulose degradation
      than in 'Dodoens', but only guaiacyl-rich lignin in 'Dodoens' plants was involved
      in successful defence against the fungus. This finding was confirmed by the
      associations of vanillin and vanillic acid with the DED-tolerant 'Dodoens' plants
      in a multivariate analysis of wood traits.

PMID- 24854169
TI  - Dynamics of leaf gas exchange, xylem and phloem transport, water potential and
      carbohydrate concentration in a realistic 3-D model tree crown.
AB  - BACKGROUND AND AIMS: Tree models simulate productivity using general gas exchange
      responses and structural relationships, but they rarely check whether leaf gas
      exchange and resulting water and assimilate transport and driving pressure
      gradients remain within acceptable physical boundaries. This study presents an
      implementation of the cohesion-tension theory of xylem transport and the Munch
      hypothesis of phloem transport in a realistic 3-D tree structure and assesses the
      gas exchange and transport dynamics. METHODS: A mechanistic model of xylem and
      phloem transport was used, together with a tested leaf assimilation and
      transpiration model in a realistic tree architecture to simulate leaf gas
      exchange and water and carbohydrate transport within an 8-year-old Scots pine
      tree. The model solved the dynamics of the amounts of water and sucrose solute in
      the xylem, cambium and phloem using a fine-grained mesh with a system of coupled
      ordinary differential equations. KEY RESULTS: The simulations predicted the
      observed patterns of pressure gradients and sugar concentration. Diurnal
      variation of environmental conditions influenced tree-level gradients in turgor
      pressure and sugar concentration, which are important drivers of carbon
      allocation. The results and between-shoot variation were sensitive to structural
      and functional parameters such as tree-level scaling of conduit size and phloem
      unloading. CONCLUSIONS: Linking whole-tree-level water and assimilate transport,
      gas exchange and sink activity opens a new avenue for plant studies, as features
      that are difficult to measure can be studied dynamically with the model. Tree
      level responses to local and external conditions can be tested, thus making the
      approach described here a good test-bench for studies of whole-tree physiology.

PMID- 24854170
TI  - Temporal variation in phenotypic gender and expected functional gender within and
      among individuals in an annual plant.
AB  - BACKGROUND AND AIMS: Adaptive explanations for variation in sex allocation centre
      on variation in resource status and variation in the mating environment. The
      latter can occur when dichogamy causes siring opportunity to vary across the
      flowering season. In this study, it is hypothesized that the widespread tendency
      towards declining fruit-set from first to last flowers on plants can similarly
      lead to a varying mating environment by causing a temporal shift in the quality
      (not quantity) of siring opportunities. METHODS: A numerical model was developed
      to examine the effects of declining fruit-set on the expected male versus female
      reproductive success (functional gender) of first and last flowers on plants, and
      of early- and late-flowering plants. Within- and among-plant temporal variation
      in pollen production, ovule production and fruit-set in 70 Brassica rapa plants
      was then characterized to determine if trends in male and female investment
      mirror expected trends in functional gender. KEY RESULTS: Under a wide range of
      model conditions, functional femaleness decreased sharply in the last flowers on
      plants, and increased from early- to late-flowering plants in the population. In
      B. rapa, pollen production decreased more rapidly than ovule production from
      first to last flowers, leading to a within-plant increase in phenotypic
      femaleness. Among plants, ovule production decreased from early- to late
      flowering plants, causing a temporal decrease in phenotypic femaleness.
      CONCLUSIONS: The numerical model confirmed that declining fruit-set can drive
      temporal variation in functional gender, especially among plants. The discrepancy
      between observed trends in phenotypic gender in B. rapa and expected functional
      gender predicted by the numerical model does not rule out the possibility that
      male reproductive success decreases with later flowering onset. If so, plants may
      experience selection for early flowering through male fitness.

PMID- 24854168
TI  - MADS goes genomic in conifers: towards determining the ancestral set of MADS-box
      genes in seed plants.
AB  - BACKGROUND AND AIMS: MADS-box genes comprise a gene family coding for
      transcription factors. This gene family expanded greatly during land plant
      evolution such that the number of MADS-box genes ranges from one or two in green
      algae to around 100 in angiosperms. Given the crucial functions of MADS-box genes
      for nearly all aspects of plant development, the expansion of this gene family
      probably contributed to the increasing complexity of plants. However, the
      expansion of MADS-box genes during one important step of land plant evolution,
      namely the origin of seed plants, remains poorly understood due to the previous
      lack of whole-genome data for gymnosperms. METHODS: The newly available genome
      sequences of Picea abies, Picea glauca and Pinus taeda were used to identify the
      complete set of MADS-box genes in these conifers. In addition, MADS-box genes
      were identified in the growing number of transcriptomes available for
      gymnosperms. With these datasets, phylogenies were constructed to determine the
      ancestral set of MADS-box genes of seed plants and to infer the ancestral
      functions of these genes. KEY RESULTS: Type I MADS-box genes are under
      represented in gymnosperms and only a minimum of two Type I MADS-box genes have
      been present in the most recent common ancestor (MRCA) of seed plants. In
      contrast, a large number of Type II MADS-box genes were found in gymnosperms. The
      MRCA of extant seed plants probably possessed at least 11-14 Type II MADS-box
      genes. In gymnosperms two duplications of Type II MADS-box genes were found, such
      that the MRCA of extant gymnosperms had at least 14-16 Type II MADS-box genes.
      CONCLUSIONS: The implied ancestral set of MADS-box genes for seed plants shows
      simplicity for Type I MADS-box genes and remarkable complexity for Type II MADS
      box genes in terms of phylogeny and putative functions. The analysis of
      transcriptome data reveals that gymnosperm MADS-box genes are expressed in a
      great variety of tissues, indicating diverse roles of MADS-box genes for the
      development of gymnosperms. This study is the first that provides a comprehensive
      overview of MADS-box genes in conifers and thus will provide a framework for
      future work on MADS-box genes in seed plants.

PMID- 24854174
TI  - Overlapping binding sites for importin beta1 and suppressor of fused (SuFu) on
      glioma-associated oncogene homologue 1 (Gli1) regulate its nuclear localization.
AB  - A key factor in oncogenesis is the transport into the nucleus of oncogenic
      signalling molecules, such as Gli1 (glioma-associated oncogene homologue 1), the
      central transcriptional activator in the Hedgehog signalling pathway. Little is
      known, however, how factors such as Gli are transported into the nucleus and how
      this may be regulated by interaction with other cellular factors, such as the
      negative regulator suppressor of fused (SuFu). In the present study we show for
      the first time that nuclear entry of Gli1 is regulated by a unique mechanism
      through mutually exclusive binding by its nuclear import factor Impbeta1
      (importin beta1) and SuFu. Using quantitative live mammalian cell imaging, we
      show that nuclear accumulation of GFP-Gli1 fusion proteins, but not of a control
      protein, is specifically inhibited by co-expression of SuFu. Using a direct
      binding assay, we show that Impbeta1 exhibits a high nanomolar affinity to Gli1,
      with specific knockdown of Impbeta1 expression being able to inhibit Gli1 nuclear
      accumulation, thus implicating Impbeta1 as the nuclear transporter for Gli1 for
      the first time. SuFu also binds to Gli1 with a high nanomolar affinity,
      intriguingly being able to compete with Impbeta1 for binding to Gli1, through the
      fact that the sites for SuFu and Impbeta1 binding overlap at the Gli1 N-terminus.
      The results indicate for the first time that the relative intracellular
      concentrations of SuFu and Impbeta1 are likely to determine the localization of
      Gli1, with implications for its action in cancer, as well as in developmental
      systems. 

PMID- 24854176
TI  - Antagonists of the P2X7 receptor: mechanism of enantioselective recognition using
      highly sulfated and sulfobutylether cyclodextrins by capillary electrokinetic
      chromatography.
AB  - This work concerns the successful enantiomeric separation of pyroglutamic acid
      derivatives, known to be P2X7 receptor antagonists, achieved by electrokinetic
      chromatography. After a broad screening, two negatively charged cyclodextrins,
      sulfobutylether-beta-cyclodextrin (SBE-beta-CD), and highly sulfated-gamma
      cyclodextrin (HS-gamma-CD) were chosen as stereoselective agents to cooperate
      with the BGE for complexation. A fused silica capillary coated with polyethylene
      oxide, filled with a phosphate buffer (25 mM, pH 2.5) containing various
      concentrations of CD, was used. Assuming a 1:1 stoichiometry, calculations of the
      binding constants, employing the three different linearization plots, were
      performed from the corrected electrophoretic mobilities values of the
      enantiomers, at different concentrations of SBE-beta-CD and HS-gamma-CD in the
      BGE. The highest complexation was found with the SBE-beta-CD. Among the three
      equations, results showed better linearity (R(2) > 0.99) using the y-reciprocal
      fit. This plotting method was then performed to determine the binding constants
      of each enantiomer at different temperature for compounds 1 and 2 with SBE-beta
      CD and HS-gamma-CD in order to access to the thermodynamic parameters of the
      eight complexes. The linearity of the Van't Hoff plot, in the range of 288-303 K
      leading to negative enthalpy values, showed that the complexation phenomenon is
      enthalpically controlled and thermodynamically favored. 

PMID- 24854178
TI  - Iron, unstable plaque and magnetic resonance imaging.

PMID- 24854177
TI  - Age may explain the association of an early dialysis initiation with poor
      survival.
AB  - BACKGROUND: Some studies postulate that early dialysis initiation may increase
      mortality. AIM: The aim of the present study was to assess to what extent this
      was due to confounding by age. DESIGN: Observational retrospective cohort study.
      METHODS: We studied all patients starting dialysis therapy between 1 January 1995
      and 31 December 2009 in our center. The following variables at dialysis
      initiation in end-stage renal disease (ESRD) patients were analysed: estimated
      glomerular filtration rate (eGFR), age, gender, diabetes mellitus, serum albumin,
      hemoglobin, period of dialysis initiation, history of ischemic heart disease and
      stroke. Multivariate Cox model was used to calculate adjusted patient survival.
      RESULTS: Over the last 15 years, 428 patients initiated dialysis therapy in our
      reference area. Median eGFR at dialysis initiation was 8.16 ml/min. In the
      univariate analysis, increased eGFR, age, dialysis initiation 1995-1999/2000
      2004, diabetes and history of ischemic heart disease were associated (P < 0.05)
      with increased mortality in ESRD. Patients that started dialysis program with
      eGFR > 8.16 were older than those who did it with eGFR < 8.16 (66 vs. 61 years, P
      < 0.001). The association between mortality and eGFR in the crude multivarite Cox
      model was lost when the model was adjusted by age. In the multivariate Cox model,
      dialysis initiation period, serum albumin and history of ischemic heart disease
      were associated with mortality. CONCLUSION: History of ischemic heart disease,
      serum albumin and dialysis start before 2005 were risk factors for mortality in
      ESRD patients. Older age is usually associated with early dialysis initiation, so
      age adjustment is needed to perform studies aimed to calculate the effect of eGFR
      at dialysis initiation on survival.

PMID- 24854175
TI  - Parasite virulence, co-infections and cytokine balance in malaria.
AB  - Strong early inflammatory responses followed by a timely production of regulatory
      cytokines are required to control malaria parasite multiplication without
      inducing major host pathology. Here, we briefly examine the homeostasis of
      inflammatory responses to malaria parasite species with varying virulence levels
      and discuss how co-infections with bacteria, viruses, and helminths can modulate
      inflammation, either aggravating or alleviating malaria-related morbidity.

PMID- 24854179
TI  - Gastric pneumatosis.

PMID- 24854180
TI  - Adenosine deaminase activity in pleural effusions of lymphoma patients.
AB  - BACKGROUND AND AIM: The purpose of this study was to assess the relationship of
      pleural adenosine deaminase (P-ADA) and non-Hodgkin's lymphoma (NHL). DESIGN AND
      METHODS: We retrospectively analysed 63 NHL patients with pleural effusions who
      accepted a diagnostic thoracentesis and who had P-ADA available at the China
      Medical University Hospital (Taichung, Taiwan) between January 2003 and April
      2012. RESULTS: There were 46 exudates [40 malignant pleural effusions (MPE), 5
      complicated para-pneumonic effusions and 1 undiagnosed effusion] and 17
      transudates. The P-ADA activity was significantly different between the two
      groups (P < 0.005). Among 40 MPE cases, 29 were due to B-cell and 11 due to T
      cell NHL. There was no pleural transudative effusion with P-ADA value higher than
      26 U/l in our study, but simultaneously 48% (22/46) of exudative pleural
      effusions showed a P-ADA value under that cut-off point. The P-ADA level reached
      the diagnostic cut-off for tuberculosis (40 IU/l) in 11 cases of MPE (11/40 =
      27.5%): 9 B-cell NHL (9/29 = 31%) and 2 T-cell NHL (2/11 = 18%). The median
      levels (25th, 75th percentiles) of P-ADA were 28 IU/l (14-50) in the MPE of B
      cell NHL and 26 IU/l (14-28) in the T-cell NHL (P = 0.693). CONCLUSIONS: The use
      of P-ADA in NHL effusion could aid the separation of transudates from exudates.
      Around one-quarter MPE of NHL had abnormal P-ADA ( > 40 IU/l). There was no
      difference in the P-ADA activity in T-cell and B-cell NHL.

PMID- 24854181
TI  - Hybrid procedure for Poland syndrome associated with a Gerbode-type defect.
AB  - Poland syndrome and Gerbode-type defect are both very rare congenital
      malformations. A combination of them is extremely uncommon and no literature has
      reported this before. We herein present a case of this combination in a 9-year
      old boy. Besides the reconstruction of the chest wall, a device closure of the
      Gerbode-type defect was also planned due to the risk of infective endocarditis.
      In order to minimize the injury, an innovative hybrid therapeutic strategy was
      chosen to treat two anomalies simultaneously in one incision. 

PMID- 24854183
TI  - Birth weight, infant growth, and adolescent blood pressure using twin status as
      an instrumental variable in a Chinese birth cohort: "Children of 1997".
AB  - PURPOSE: To evaluate the credibility of twin status as an instrumental variable
      for birth weight and infant growth and to obtain less-confounded estimates of the
      associations of birth weight or infant growth with adolescent blood pressure
      (BP). METHODS: Prospective population-based "Children of 1997" birth cohort of
      all surviving infants born in Hong Kong, China, from April to May 1997 with sex-,
      age-, and height-specific BP z-score at approximately 11 years (n = 6276) and
      approximately 13 years (n = 5305). RESULTS: In instrumental variable analyses,
      birth weight-for-gestational age z-score was not associated with z-score for
      systolic BP (0.01; 95% confidence interval [CI], -0.22 to 0.25) or diastolic BP
      (0.04; 95% CI, -0.09 to 0.18) at approximately 11 years adjusted for maternal age
      and migrant status (F = 38.6). Change in weight z-score at 0 to 12 months was not
      associated with z-score for systolic BP (-0.003; 95% CI, -0.15 to 0.15) or
      diastolic BP (-0.02; 95% CI, -0.10 to 0.07) at approximately 11 years (F = 54.4).
      Estimates were similar for BP at approximately 13 years, although the F-statistic
      was lower. CONCLUSIONS: Birth weight and infant growth may make little
      contribution to adolescent BP. Extending consideration of the effects of early
      life to other growth periods, such as puberty, on BP might yield public health
      benefits.

PMID- 24854184
TI  - A simple example as a pedagogical device?

PMID- 24854182
TI  - Using a physician panel to estimate food allergy prevalence in a longitudinal
      birth cohort.

PMID- 24854186
TI  - Abstracts of the 49th Congress of the European Society for Surgical Research, May
      21-24, 2014, Budapest, Hungary.

PMID- 24854185
TI  - Serum cotinine and whole blood folate concentrations in pregnancy.
AB  - PURPOSE: Prenatal tobacco smoke exposure may be associated with low maternal
      folate levels that increase the risk of adverse infant and child health outcomes
      by reducing folate availability during fetal development. METHODS: Using data
      from the Health Outcomes and Measures of the Environment Study, we examined the
      relationship between secondhand or active tobacco smoke exposure and whole blood
      folate concentrations in pregnant women from Cincinnati, Ohio (n = 362) at
      approximately 16-week gestation. We used multivariable linear regression to
      examine the association between continuous or categorical serum cotinine levels
      and whole blood folate levels, adjusting for sociodemographic, dietary, and
      perinatal variables. RESULTS: After adjustment for potential confounders, an
      interquartile range increases in serum cotinine concentration (0.012-0.224 ng/mL)
      was suggestively associated with decreased whole blood folate levels (beta, -23
      nmol/L; 95% confidence interval (CI), -49, 3; P value = .08). Compared with
      unexposed women, reductions in mean whole blood folate were observed among active
      smokers (beta, -94, 95% CI, 195, 6 nmol/L; P value = .40); smaller reductions
      were observed among women with secondhand exposure (beta, 26; CI, 84, 32 nmol/L;
      P value = .07). CONCLUSIONS: Consistent with prior studies, active smoking was
      associated with reduced whole blood folate levels among these pregnant women.
      Secondhand tobacco smoke exposures were associated with small and imprecise
      reductions in whole blood folate levels.

PMID- 24854187
TI  - [Leg ischemia complicating the intraosseous infusion of epinephrine for a
      Djiboutian child].
AB  - Intraosseous infusion is increasingly used as an alternative to intravenous
      infusion. It is recommended for the cardiac arrest of a child in the first
      instance and after two failed attempts of intravenous infusion in the cardiac
      arrest of adults. Its rapid use and its low failure rate justify its use in all
      life-threatening emergencies. It can be used to administer the same treatments as
      intravenous infusion. It does, nonetheless, present some rare complications, such
      as acute leg ischemia by extravasation of epinephrine, as we report here.
      Awareness of these complications is necessary to ensure compliance with the rules
      of placing this type of infusion. 

PMID- 24854188
TI  - Low-cost mobile phone microscopy with a reversed mobile phone camera lens.
AB  - The increasing capabilities and ubiquity of mobile phones and their associated
      digital cameras offer the possibility of extending low-cost, portable diagnostic
      microscopy to underserved and low-resource areas. However, mobile phone
      microscopes created by adding magnifying optics to the phone's camera module have
      been unable to make use of the full image sensor due to the specialized design of
      the embedded camera lens, exacerbating the tradeoff between resolution and field
      of view inherent to optical systems. This tradeoff is acutely felt for diagnostic
      applications, where the speed and cost of image-based diagnosis is related to the
      area of the sample that can be viewed at sufficient resolution. Here we present a
      simple and low-cost approach to mobile phone microscopy that uses a reversed
      mobile phone camera lens added to an intact mobile phone to enable high quality
      imaging over a significantly larger field of view than standard microscopy. We
      demonstrate use of the reversed lens mobile phone microscope to identify red and
      white blood cells in blood smears and soil-transmitted helminth eggs in stool
      samples. 

PMID- 24854190
TI  - Perceptions of lethal fetal abnormality among perinatal professionals and the
      challenges of neonatal palliative care.
AB  - BACKGROUND: After prenatal diagnosis of lethal fetal abnormality (LFA), some
      couples choose to continue the pregnancy rather than opt for termination of the
      pregnancy. This may result in the requirement for neonatal palliative care, which
      in France is prescribed by the Leonetti Law. These rare situations raise various
      questions about when and how palliative care is provided in cases of LFA.
      OBJECTIVE: The main goal of the study was to clarify the place given to the
      concept of perinatal palliative care within the antenatal information provided by
      perinatal professionals. This work was specifically aimed at revealing
      caregivers' perceptions of and attitudes toward LFA, how it is managed, and
      procedures for decision making and providing information. METHODS: This is a
      qualitative study using focus groups from two French Multidisciplinary Centers
      for Prenatal Diagnosis. All verbal production (individual statements, verbal
      exchanges, etc.) produced during the two focus groups was fully transcribed and
      the content analyzed. RESULTS: Content analysis revealed four main themes: (1)
      defining LFA; (2) the source and nature of information about LFA and how it is
      communicated; (3) therapeutic options and decisions in the management of LFA; and
      (4) palliative care (limits and criteria) in the context of LFA. CONCLUSIONS:
      Consistency as regards the perceived intention of care among all members of the
      health care team is essential to support parents facing a possible fatal outcome.
      Attitudes and practices at Multidisciplinary Centers for Prenatal Diagnosis need
      to be shaped on a national basis.

PMID- 24854191
TI  - [Primary erythromelalgia].

PMID- 24854189
TI  - Does chronic obstructive pulmonary disease with or without type 2 diabetes
      mellitus influence the risk of lung cancer? Result from a population-based cohort
      study.
AB  - BACKGROUND: Previous studies have suggested that chronic obstructive pulmonary
      disease (COPD) is an independent risk factor for lung cancer. There are some
      evidence that people with diabetes are at a risk of developing many forms of
      cancer, but inconclusive with regard to lung cancer. The aim of this study was to
      evaluate whether COPD with or without type 2 diabetes mellitus (T2DM) influences
      the risk of developing lung cancer. METHODS: This is a retrospective cohort study
      consisting of 20,730 subjects newly diagnosed with COPD ("cases"). Their data was
      collected from the National Health Insurance system of Taiwan from 1998 to 2010.
      Among these patients, 5,820 patients had T2DM and 14,910 patients did not have
      T2DM. The retrospective matched control group consisted of 20,729 subjects
      without either COPD or T2DM. The control group was matched with the cases for
      sex, age, and index year (the year that the patient was diagnosed with COPD). The
      subjects were followed until the end of 2011. RESULTS: The findings of our study
      showed that the risk of lung cancer was higher in the COPD group than in the non
      COPD group, with adjusted hazard ratio (HR) of 5.02 [95% confidence interval (CI)
      = 4.23-5.94] among total case group, adjusted HR was 5.38 (95% CI = 4.52-6.40) in
      the cohort without T2DM and adjusted HR was 4.05 (95% CI = 3.26-5.03) in the
      cohort with T2DM. We observed a significantly protective effect from lung cancer
      (adjusted HR = 0.75, 95% CI = 0.63-0.90) of diabetic cohort than non-diabetic
      cohort among patients with COPD. CONCLUSION: Patients with COPD had a
      significantly higher risk of developing lung cancer than healthy people. However,
      there was a protective effect of T2DM for lung cancer among patients with COPD.
      Further investigation may be needed to corroborate the mechanism or bring up
      reliable reasons.

PMID- 24854192
TI  - [Pulmonary embolism in a patient with familial thrombophilia due to homozygotic
      genetic mutation in 20209C>T].

PMID- 24854194
TI  - [Animal experimentation and progress in medicine].

PMID- 24854193
TI  - [Molecular characterization of atypical chronic myeloid leukemia and chronic
      neutrophilic leukemia].
AB  - BACKGROUND AND OBJECTIVE: Atypical chronic myeloid leukemia (aCML) and chronic
      neutrophilic leukemia (CNL) display similar clinical and hematological
      characteristics. The objective of the present study was to determine the
      mutational status of SETBP1 and CSF3R in these diseases. PATIENTS AND METHOD: The
      mutational status of SETBP1 and CSF3R was studied in 7 patients with aCML (n =
      3), CNL (n = 1) and unclassifiable myeloproliferative neoplasms (MPN-u) (n = 3).
      Additionally, mutations in ASXL1, SRSF2, IDH1/2, DNMT3A, and RUNX1 were also
      analyzed. RESULTS: SETBP1 mutations (G870S and G872R) were detected in 2 patients
      with MPN-u, and one of them also presented mutations in SRSF2 (P95H) and ASXL1
      (E635fs). The CNL case showed mutations in CSFR3 (T618I), SETBP1 (G870S) and
      SRSF2 (P95H). No patient classified as aCML had mutations in SETBP1 or CSF3R. One
      of the patients with mutations evolved to acute myeloid leukemia, while the other
      2 had disease progression without transformation to overt leukemia. CONCLUSION:
      The knowledge of the molecular alterations involved in these rare diseases is
      useful in the diagnosis and may have an impact on both prognosis and therapy.

PMID- 24854195
TI  - Outcome of hemiarthroplasty and total hip replacement for active elderly patients
      with displaced femoral neck fractures: a meta-analysis of 8 randomized clinical
      trials.
AB  - BACKGROUND: Displaced fracture of the femoral neck has been a common clinical
      problem, especially in aged patients. However, the optimal treatment choice
      remains controversial. The purpose of this study is to conduct a systematic
      review of randomized clinical trials assessing the results of hemiarthroplasty
      and total hip replacement in patients undergoing either alternative using meta
      analysis. METHODS: A literature search for randomized clinical trials was
      conducted through Medline, Embase and Cochrane library between 1969 and 2013 with
      no restrictions. Additional relevant articles were referred as source of
      information by way of manual searches on major orthopedic journals. Upon the
      search, two authors independently evaluated study quality and relevant data was
      extracted. RESULTS: A total of 8 studies with 983 patients were included in this
      meta-analysis. After pooling the available data, a significant dominance of
      Harris hip score was found for total hip replacement compared with
      hemiarthroplasty (SMD: -7.11, 95%:-10.70,-3.53) one year postoperatively and the
      advantage kept over (SMD: -6.91, 95%:-12.98, -0.85) two years after surgery. A
      trend toward a higher dislocation rate was found in total hip replacement group
      (RR: 0.46, 95%: 0.21, 1.02), of which the difference was considered
      insignificant. The risk of revision in group hemiarthroplasty appeared to be more
      than two folds higher than that after total hip replacement (RR: 4.14, 95%CI:
      2.09, 8.19). CONCLUSION: Even though there is a higher rate of dislocation after
      total hip replacement, this disadvantage could be accounted for, on the basis of
      a better functional score and the lower revision rate. However, from the results,
      it stands to reason that total hip replacement should be strongly suggested in
      elderly active patients with femoral neck fracture.

PMID- 24854196
TI  - High parasitological failure rate of visceral leishmaniasis to sodium
      stibogluconate among HIV co-infected adults in Ethiopia.
AB  - BACKGROUND: Antimonials are still being used for visceral leishmaniasis (VL)
      treatment among HIV co-infected patients in East-Africa due to the shortage of
      alternative safer drugs like liposomal amphotericin B. Besides tolerability,
      emergence of resistance to antimonials is a major concern. OBJECTIVES: This study
      was aimed at assessing the clinical outcome of VL-HIV co-infected patients when
      treated with sodium stibogluconate (SSG). METHODS: Retrospective patient record
      analysis of VL-HIV co-infected patients treated at a clinical trial site in north
      west Ethiopia was done. Patients with parasitologically confirmed VL and HIV co
      infection treated with SSG were included. The dose of SSG used was 20 mg Sb5
      (pentavalent antimony)/kg and maximum of 850 mg Sb5 for 30 days. The clinical
      outcomes were defined based on the tissue aspiration results as cure or failure,
      and additionally the safety and mortality rates were computed. RESULTS: The study
      included 57 patients treated with SSG and by the end of treatment only 43.9% of
      patients were cured. The parasitological treatment failure and the case fatality
      rate were 31.6% and 14.0% respectively. SSG was discontinued temporarily or
      permanently for 12 (21.1%) cases due to safety issues. High baseline parasite
      load (graded more than 4+) was significantly associated with treatment failure
      (odds ratio = 8.9, 95% confidence interval = .5-51.7). CONCLUSION: SSG is not
      only unsafe, but also has low effectiveness for VL-HIV patients. Safe and
      effective alternative medications are very urgently needed. Drug sensitivity
      surveillance should be introduced in the region.

PMID- 24854197
TI  - Reducing effect of IL-32alpha in the development of stroke through blocking of NF
      kappaB, but enhancement of STAT3 pathways.
AB  - Neuroinflammation is important for the development of several neurodegenerative
      diseases such as Alzheimer's disease, Parkinson's disease, and stroke. Since
      changes of cytokine level are critical for neuroinflammation in the brain, we
      investigated whether IL-32alpha overexpression could change neuroinflammation
      and, thus, affect stroke development. Middle cerebral artery occlusion (MCAO)
      induced development of ischemia, and ischemic neuronal cell death were reduced in
      IL-32alpha-overexpressing transgenic mice (IL-32alpha mice) brain through the
      decreased release of neuroinflammatory cytokines (IL-6, IL-1beta, TNF-alpha) and
      activation of astrocytes, but enhancement of anti-neuroinflammatory cytokines (IL
      10). Reactive oxygen species generation and lipid peroxidation as well as
      expression of inducible nitric oxide and cyclooxygenase-2 were also reduced in
      the IL-32alpha mice brain. Nuclear factor-kappa B (NF-kappaB), a critical
      transcriptional factor regulating neuroinflammation, was much lower, but
      activation of signal transducer and activator of transcription 3 (STAT3), which
      plays a crucial role in cell survival and proliferation, was much higher in IL
      32alpha-overexpressing mice brain compared to those of wild-type mice brain.
      These results suggest that IL-32alpha can prevent cerebral ischemia damage via
      upregulation of anti-neuroinflammatory cytokine expression and STAT3 activation,
      but downregulation of neuroinflammatory cytokines and NF-kappaB activation.

PMID- 24854198
TI  - Valproic acid alleviates memory deficits and attenuates amyloid-beta deposition
      in transgenic mouse model of Alzheimer's disease.
AB  - In the brains of patients with Alzheimer's disease (AD) and transgenic AD mouse
      models, astrocytes and microglia activated by amyloid-beta (Abeta) contribute to
      the inflammatory process that develops around injury in the brain. Valproic acid
      (VPA) has been shown to have anti-inflammatory function. The present study
      intended to explore the therapeutic effect of VPA on the neuropathology and
      memory deficits in APPswe/PS1DeltaE9 (APP/PS1) transgenic mice. Here, we report
      that VPA-treated APP/PS1 mice markedly improved memory deficits and decreased
      Abeta deposition compared with the vehicle-treated APP/PS1 mice. Moreover, the
      extensive astrogliosis and microgliosis as well as the increased expression in
      interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) in the
      hippocampus and cortex of APP/PS1 transgenic mice were significantly reduced
      following administration of VPA, which attenuated neuronal degeneration.
      Concomitantly, VPA alleviated the levels of p65 NF-kappaB phosphorylation and
      enhanced the levels of acetyl-H3, Bcl-2, and phospho-glycogen synthase kinase
      (GSK)-3beta that occurred in the hippocampus of APP/PS1 transgenic mice. These
      results demonstrate that VPA could significantly ameliorate spatial memory
      impairment and Abeta deposition at least in part via the inhibition of
      inflammation, suggesting that administration of VPA could provide a therapeutic
      approach for AD.

PMID- 24854199
TI  - Standardized handwriting to assess bradykinesia, micrographia and tremor in
      Parkinson's disease.
AB  - OBJECTIVE: To assess whether standardized handwriting can provide quantitative
      measures to distinguish patients diagnosed with Parkinson's disease from age- and
      gender-matched healthy control participants. DESIGN: Exploratory study. Pen tip
      trajectories were recorded during circle, spiral and line drawing and repeated
      character 'elelelel' and sentence writing, performed by Parkinson patients and
      healthy control participants. Parkinson patients were tested after overnight
      withdrawal of anti-Parkinsonian medication. SETTING: University Medical Center
      Groningen, tertiary care, the Netherlands. PARTICIPANTS: Patients with
      Parkinson's disease (n = 10; mean age 69.0 years; 6 male) and healthy controls (n
      = 10; mean age 68.1 years; 6 male). INTERVENTIONS: Not applicable. MAIN OUTCOME
      MEASURES: Movement time and velocity to detect bradykinesia and the size of
      writing to detect micrographia. A rest recording to investigate the presence of a
      rest-tremor, by frequency analysis. RESULTS: Mean disease duration in the
      Parkinson group was 4.4 years and the patients were in modified Hoehn-Yahr stages
      1-2.5. In general, Parkinson patients were slower than healthy control
      participants. Median time per repetition, median velocity and median acceleration
      of the sentence task and median velocity of the elel task differed significantly
      between Parkinson patients and healthy control participants (all p<0.0014).
      Parkinson patients also wrote smaller than healthy control participants and the
      width of the 'e' in the elel task was significantly smaller in Parkinson patients
      compared to healthy control participants (p<0.0014). A rest-tremor was detected
      in the three patients who were clinically assessed as having rest-tremor.
      CONCLUSIONS: This study shows that standardized handwriting can provide objective
      measures for bradykinesia, tremor and micrographia to distinguish Parkinson
      patients from healthy control participants.

PMID- 24854200
TI  - Separation of nine compounds from Salvia plebeia R.Br. using two-step high-speed
      counter-current chromatography with different elution modes.
AB  - Nine compounds were successfully separated from Salvia plebeia R.Br. using two
      step high-speed counter-current chromatography with three elution modes. Elution
      extrusion counter-current chromatography was applied in the first step, while
      classical counter-current chromatography and recycling counter-current
      chromatography were used in the second step. Three solvent systems, n
      hexane/ethyl acetate/ethanol/water (4:6.5:3:7, v/v), methyl tert-butyl
      ether/ethyl acetate/n-butanol/methanol/water (6:4:1:2:8, v/v) and n-hexane/ethyl
      acetate/methanol/water (5:5.5:5:5, v/v) were screened and optimized for the two
      step separation. The separation yielded nine compounds, including caffeic acid
      (1), 6-hydroxyluteuolin-7-glucoside (2), 5,7,3',4'-tetrahydroxy-6
      methoxyflavanone-7-glucoside (3), nepitrin (4), rosmarinic acid (5),
      homoplantaginin (6), nepetin (7), hispidulin (8), and 5,6,7,4'
      tertrahydroxyflavone (9). To the best of our knowledge, 5,7,3',4'-tetrahydroxy-6
      methoxyflavanone-7-glucoside and 5,6,7,4'-tertrahydroxyflavone have been
      separated from Salvia plebeia R.Br. for the first time. The purities and
      structures of these compounds were identified by high-performance liquid
      chromatography, electrospray ionization mass spectrometry, (1)H and (13)C NMR
      spectroscopy. This study demonstrates that high-speed counter-current
      chromatography is a useful and flexible tool for the separation of components
      from a complex sample.

PMID- 24854201
TI  - Recombinant human L-ficolin directly neutralizes hepatitis C virus entry.
AB  - L-ficolin is a soluble pattern recognition molecule expressed by the liver that
      contributes to innate immune defense against microorganisms. It is well described
      that binding of L-ficolin to specific pathogen-associated molecular patterns
      activates the lectin complement pathway, resulting in opsonization and lysis of
      pathogens. In this study, we demonstrated that in addition to this indirect
      effect, L-ficolin has a direct neutralizing effect against hepatitis C virus
      (HCV) entry. Specific, dose-dependent binding of recombinant L-ficolin to HCV
      glycoproteins E1 and E2 was observed. This interaction was inhibited by soluble L
      ficolin ligands. Interaction of L-ficolin with E1 and E2 potently inhibited entry
      of retroviral pseudoparticles bearing these glycoproteins. L-ficolin also
      inhibited entry of cell-cultured HCV in a calcium-dependent manner. Neutralizing
      concentrations of L-ficolin were found to be circulating in the serum of HCV
      infected individuals. This is the first description of direct neutralization of
      HCV entry by a ficolin and highlights a novel role for L-ficolin as a virus entry
      inhibitor.

PMID- 24854203
TI  - 2,4-Dichlorophenoxyacetic acid alters intracellular pH and ion transport in the
      outer mantle epithelium of the bivalve Anodonta cygnea.
AB  - Bivalve molluscs, due to their sedentary mode of life and filter-feeding
      behavior, are very susceptible to pollutant bioaccumulation and used as sentinel
      organisms in the assessment of environment pollution. Herein we aimed to
      determine the in vivo, ex vivo and in vitro effects of 2,4-dichlorophenoxyacetic
      acid (2,4-D), a widely used herbicide, in Anodonta cygnea shell growth
      mechanisms. For that, we evaluated the effect of 2,4-D (100 MUM) exposure on the
      transepithelial short-circuit current (Isc), potential (Vt) and conductance (Gt),
      as well as on OME ion transport systems and intracellular pH (pHi). In vivo
      exposure to 2,4-D caused an increase of 50% on the Isc generated by OME and ex
      vivo addition of that compound to the apical side of OME also induced an Isc
      increase. Furthermore, 2,4-D was able to cause a pHi increase in isolated cells
      of OME. Noteworthy, when 2,4-D was added following the exposure to specific
      inhibitors of several membrane transporters identified as responsible for pHi
      maintenance in these cells, no significant effect was observed on pHi except when
      the V-type ATPase inhibitor was used, indicating an overlap with the effect of
      2,4-D. Thus, we concluded that 2,4-D is able of enhancing the activity of the V
      ATPases present on the OME of A. cygnea and that this effect seems to be due to a
      direct stimulation of those H(+) transporters present on the apical portion of
      the membrane of OME cells, which are vital for shell maintenance and growth. This
      study allows us to better understand the molecular mechanisms behind 2,4-D
      toxicity and its deleterious effect in aquatic ecosystems, with particular
      emphasis on those involved in shell formation of bivalves.

PMID- 24854204
TI  - Isolation, structural elucidation and anti-inflammatory activity of astragalin, (
      )hinokinin, aristolactam I and aristolochic acids (I & II) from Aristolochia
      indica.
AB  - Astragalin was isolated for the first time along with (-)hinokinin, aristolactam
      I and aristolochic acids (I & II) from the extracts of Aristolochia indica L.
      using a new, efficient preparative HPLC method. A reversed-phase HPLC method of
      analysis was developed to analyse the isolated compounds. The crude extracts and
      the isolated compounds were tested for their anti-inflammatory potential. We
      report here for the first time the anti-inflammatory effects of (-)hinokinin and
      aristolactam I against IL-6 (IC50 = 20.5 +/- 0.5 and 52 +/- 8 MUM) and TNFalpha
      (IC50 = 77.5 +/- 27.5 and 116.8 +/- 83.25 MUM), respectively. (-)Hinokinin
      exerted its anti-inflammatory effects via NFkappaB-dependent mechanism whereas
      aristolactam I may be effective via a mechanism independent of NFkappaB.

PMID- 24854205
TI  - Development of a method for measuring femoral torsion using real-time ultrasound.
AB  - Excessive femoral torsion has been associated with various musculoskeletal and
      neurological problems. To explore this relationship, it is essential to be able
      to measure femoral torsion in the clinic accurately. Computerized tomography (CT)
      and magnetic resonance imaging (MRI) are thought to provide the most accurate
      measurements but CT involves significant radiation exposure and MRI is expensive.
      The aim of this study was to design a method for measuring femoral torsion in the
      clinic, and to determine the reliability of this method. Details of design
      process, including construction of a jig, the protocol developed and the
      reliability of the method are presented. The protocol developed used ultrasound
      to image a ridge on the greater trochanter, and a customized jig placed on the
      femoral condyles as reference points. An inclinometer attached to the customized
      jig allowed quantification of the degree of femoral torsion. Measurements taken
      with this protocol had excellent intra- and inter-rater reliability (ICC2,1 =
      0.98 and 0.97, respectively). This method of measuring femoral torsion also
      permitted measurement of femoral torsion with a high degree of accuracy. This
      method is applicable to the research setting and, with minor adjustments, will be
      applicable to the clinical setting. 

PMID- 24854206
TI  - Extent of lymph node dissection at nephrectomy affects cancer-specific survival
      and metastatic progression in specific sub-categories of patients with renal cell
      carcinoma (RCC).
AB  - OBJECTIVE: To test whether the number of lymph nodes removed affects cancer
      specific survival (CSS) or metastatic progression-free survival (MPFS) in
      different renal cell carcinoma (RCC) scenarios. METHODS: We used Cox regression
      analyses to analyse the effect of the number of lymph nodes removed on CSS and
      MPFS in 1983 patients with RCC treated with nephrectomy. To adjust for possible
      clinical and surgical selection bias, analyses were further adjusted for number
      of positive nodes, presence of metastases, age, performance status, T stage,
      tumour size and grade. RESULTS: The prevalence of lymph node invasion was 6.1%.
      The mean follow-up period was 83.3 months. Multivariable analyses showed that the
      number of nodes removed had an independent, protective effect on CSS in patients
      with pT2a-pT2b or pT3c-pT4 RCC (hazard ratio [HR] 0.91, P = 0.008 and HR 0.89, P
      < 0.001, respectively), in patients with bulky tumours (tumour size >10 cm, HR
      0.97, P = 0.03) or when sarcomatoid features were found (HR 0.81, P = 0.006). The
      removal of each additional lymph node was associated with a 3-19% increase in
      CSS. When considering MPFS as an endpoint, the number of nodes removed had an
      independent, protective effect in the same patient categories. CONCLUSIONS: When
      clinically indicated, the number of nodes removed affects CSS and MPFS in
      specific sub-categories of patients with RCC.

PMID- 24854207
TI  - Quantitative analysis of staphylococcus enterotoxin A by differential expression
      of IFN-gamma in splenocyte and CD4+ T-cells.
AB  - Staphylococcus aureus is an important bacterial pathogen that produces a range of
      Staphylococcal Enterotoxins (SEs) which cause gastroenteritis and superantigen
      activation of T cells, the mechanism of which is not well understood. The ability
      to rapidly detect and quantify SEs is very important in order to learn the causes
      of staphylococcal outbreaks and to stop similar outbreaks in the future. Enzyme
      linked immunosorbent assays (ELISAs) have been developed for detection of several
      SEs. However, these immunological methods cannot distinguish between active and
      inactive toxin. It is known that interferon-gamma (IFN-gamma) expressed in
      response to stimulation by SEs contributes significantly to the pathogenesis of
      S. aureus infection. Nonetheless, the cellular source of IFN-gamma is still
      unclear and the contributions of the specific splenocyte types. In our effort to
      understand the immunologic response to Staphylococcal Enterotoxin A (SEA)
      exposure, we studied IFN-gamma production in mouse splenocytes. We demonstrated
      that short term ex vivo exposure of splenocytes or primary naive CD4+ T-cells to
      biologically active SEA induces differential expression of IFN-gamma mRNA in a
      time and dose dependent manner and the expression levels reflect the levels of
      IFN-gamma secreted protein. Positive isolated CD4+ T-cells accounted for only 10%
      of IFN-gamma production. We also demonstrate that expression of IFN-gamma can be
      used for rapid quantitative analysis of active SEA with a detection limit of 1
      ng/mL. 

PMID- 24854208
TI  - A multispectral photon-counting double random phase encoding scheme for image
      authentication.
AB  - In this paper, we propose a new method for color image-based authentication that
      combines multispectral photon-counting imaging (MPCI) and double random phase
      encoding (DRPE) schemes. The sparsely distributed information from MPCI and the
      stationary white noise signal from DRPE make intruder attacks difficult. In this
      authentication method, the original multispectral RGB color image is down-sampled
      into a Bayer image. The three types of color samples (red, green and blue color)
      in the Bayer image are encrypted with DRPE and the amplitude part of the
      resulting image is photon counted. The corresponding phase information that has
      nonzero amplitude after photon counting is then kept for decryption. Experimental
      results show that the retrieved images from the proposed method do not visually
      resemble their original counterparts. Nevertheless, the original color image can
      be efficiently verified with statistical nonlinear correlations. Our experimental
      results also show that different interpolation algorithms applied to Bayer images
      result in different verification effects for multispectral RGB color images. 

PMID- 24854209
TI  - A vision-based system for intelligent monitoring: human behaviour analysis and
      privacy by context.
AB  - Due to progress and demographic change, society is facing a crucial challenge
      related to increased life expectancy and a higher number of people in situations
      of dependency. As a consequence, there exists a significant demand for support
      systems for personal autonomy. This article outlines the vision@home project,
      whose goal is to extend independent living at home for elderly and impaired
      people, providing care and safety services by means of vision-based monitoring.
      Different kinds of ambient-assisted living services are supported, from the
      detection of home accidents, to telecare services. In this contribution, the
      specification of the system is presented, and novel contributions are made
      regarding human behaviour analysis and privacy protection. By means of a multi
      view setup of cameras, people's behaviour is recognised based on human action
      recognition. For this purpose, a weighted feature fusion scheme is proposed to
      learn from multiple views. In order to protect the right to privacy of the
      inhabitants when a remote connection occurs, a privacy-by-context method is
      proposed. The experimental results of the behaviour recognition method show an
      outstanding performance, as well as support for multi-view scenarios and real
      time execution, which are required in order to provide the proposed services. 

PMID- 24854210
TI  - O-acetylation of low-molecular-weight polysaccharide from Enteromorpha linza with
      antioxidant activity.
AB  - Polysaccharide extracted from green algae Enteromorpha linza (EP) is a sulfated
      polysaccharide, which possesses excellent antioxidant activities. In present
      study, the acetylated derivatives of low-molecular-weight polysaccharide (LEP)
      was prepared with the method of response surface quadratic model. And then the
      antioxidant activities of the derivatives were investigated including scavenging
      effects of superoxide and hydroxyl radicals. The results of chemical analysis and
      FT-IR spectrum showed the acetylation was successful. And in addition, certain
      derivative with different degree of substitution (DS) exhibited different
      antioxidant activity. 

PMID- 24854211
TI  - Production of hexaoligochitin from colloidal chitin using a chitinase from
      Aeromonas schubertii.
AB  - Chitin derivatives, such as those with modified main saccharide chains and
      deacetylated side chains, exhibit versatile biological functions. The biomedical
      properties of chitin oligosaccharides depend on their degree of oligomerization.
      Of the chitin oligosaccharides, chitin hexamers are generally the most potent. In
      our recent study, N-acetylchitohexaose was obtained by digesting chitin with
      ASCHI61, a chitinase from Aeromonas schubertii. In this work, the factors
      involved in the production of chitin hexasaccharide were evaluated
      experimentally. Using steep map analysis and cross-analysis, the substrate
      concentration and reaction pH were identified as the key factors in this
      reaction, and the interactions between these parameters were observed. Using a
      response surface experimental design, we predicted that a colloidal chitin
      concentration of 3.4mgmL(-1) and a pH of 6.54 were the optimal conditions for
      producing hexaoligochitin. These conditions were verified in separate
      experiments, in which 38.73mmolL(-1) of N-acetylchitohexaose was obtained. The
      maximum amount of hexamer produced was 42.175mgL(-1), an increase of only 0.27%
      from the predicted value. 

PMID- 24854212
TI  - Docetaxel load biodegradable porous microspheres for the treatment of colorectal
      peritoneal carcinomatosis.
AB  - Micro- and nanoparticle formulations are widely used to improve the
      bioavailability of low solubility drugs. In this study, biodegradable poly(L
      lactide acid)-Pluronic L121-poly(L-lactide acid) (PLLA-L121-PLLA) was developed.
      And then a controlled drug delivery system (CDDS), docetaxel (DOC) loaded PLLA
      L121-PLLA porous microsphere (DOC MS) was prepared for colorectal peritoneal
      carcinomatosis (CRPC) therapy. DOC MS was prepared by DOC and PLLA-L121-PLLA
      using an oil-in-water emulsion solvent evaporation method. The particle size,
      morphological characteristics, encapsulation efficiency, in vitro drug release
      studies and in vitro cytotoxicity of DOC MS have been investigated. In vitro
      release profile demonstrated a significant difference between rapid release of
      free DOC and much slower and sustained release of DOC MS. Furthermore,
      cytotoxicity assay indicated cytotoxicity was increased after DOC was
      encapsulated into polymeric microspheres. In addition, intraperitoneal
      administration of DOC MS could effectively suppress growth and metastasis of CT26
      peritoneal carcinomatosis in vivo, and prolonged the survival of tumor bearing
      mice. Immunohistochemistry staining of tumor tissues with Ki-67 revealed that DOC
      MS induced a stronger anti-tumor effect by increasing apoptosis of tumor cells in
      contrast to other groups (P<0.05). Thus, our results suggested that DOC MS may
      have great potential applications in clinic. 

PMID- 24854213
TI  - Isolation, characterization and investigation of Plantago ovata husk
      polysaccharide as superdisintegrant.
AB  - Psyllium husk (Plantago ovata, Family: Plantaginaceae) contains a high proportion
      of hemicellulose, composed of a xylan backbone linked with arabinose, rhamnose,
      and galacturonic acid units (arabinoxylans). Polysaccharide was isolated from
      Psyllium husk using solvent precipitation method. The isolated polysaccharide was
      evaluated for various physicochemical parameters. The rheological behavior of
      polysaccharide (1% w/v in water) was studied using Brookfield viscometer.
      Polysaccharide derived from the husk of P. ovata was investigated as
      superdisintegrant in the fast dissolving tablets. Valsartan, an antihypertensive
      drug, was selected as a model drug. The tablets of Valsartan were prepared
      separately using different concentrations (1, 2.5, 5, 7.5% w/w) of isolated
      Plantago ovata (P. ovata) husk polysaccharide (Natural) and crospovidone as a
      synthetic superdisintegrant by direct compression method. The prepared tablets
      were evaluated for various pre-compression and post-compression parameters. The
      drug excipient interactions were characterized by FTIR studies. The formulation
      F4 containing7.5% polysaccharide showed rapid wetting time and disintegration
      time as compared to formulation prepared using synthetic superdisintegrant at the
      same concentration level. Hence batch F4 was considered as optimized formulation.
      The stability studies were performed on formulation F4. The disintegration time
      and in vitro drug release of the optimized formulation was compared with the
      marketed formulation (Conventional tablets). 

PMID- 24854214
TI  - Preface. Antiparasitic drug use and resistance in cattle, small ruminants and
      equines in the United States--current status and global perspectives.

PMID- 24854216
TI  - Treatment of atrial fibrillation in East Asia: what is perception and what is
      reality?

PMID- 24854215
TI  - Multicenter experience with extraction of the Riata/Riata ST ICD lead.
AB  - BACKGROUND: In November 2011, the Food and Drug Administration issued a class I
      recall of Riata and Riata ST implantable cardioverter-defibrillator leads.
      Management recommendations regarding the recall have remained controversial.
      OBJECTIVE: Data regarding the safety and feasibility of extraction of Riata
      implantable cardioverter-defibrillator leads are limited. METHODS: We performed a
      retrospective study of patients undergoing extraction of Riata/Riata ST leads at
      11 centers. RESULTS: Between July 2003 and April 2013, 577 Riata/Riata ST leads
      were extracted from 577 patients (Riata 467, [84%]; Riata ST 89, [16%]). Complete
      procedural success achieved in 99.1%. The cohort was 78% men, with a mean age of
      60 years and a mean left ventricular ejection fraction of 34% +/- 14%. The mean
      implant duration was 44.7 months (range 0-124.6 months). The majority of leads
      extracted were for infection (305 [53.0%]) and 220 (35.7%) for lead malfunction.
      Evaluation for lead integrity was performed in 295 cases. Of these, 34.9% were
      found to have externalized cables. Implant duration was significantly longer in
      leads with externalized cables (P < .0001). No difference in lead integrity was
      noted between Riata and Riata ST leads (11.7% vs. 17.7% failure; P = .23). Among
      leads in which cable externalization was noted, laser sheaths were used more
      frequently (P = .01). Major complications included 3 superior vena cava/right
      ventricular perforations requiring surgical intervention with 1 death 12 days
      after the procedure and 1 pericardial effusion requiring percutaneous drainage
      (0.87%). CONCLUSION: Extraction of the Riata/Riata ST leads can be challenging,
      and leads with externalized cables may require specific extraction techniques.
      Extraction of the Riata/Riata ST leads can be performed safely by experienced
      operators at high-volume centers with a complication rate comparable to published
      data.

PMID- 24854218
TI  - Coping among military veterans with PTSD in substance use disorder treatment.
AB  - We longitudinally investigated coping among male military veterans (n = 98) with
      posttraumatic stress disorder (PTSD) symptomatology and a co-occurring substance
      use disorder (SUD) who participated in a randomized controlled trial of seeking
      safety (SS). Participants were randomized to SS or intensive treatment-as-usual
      (TAU) for SUD. Coping (active, avoidant, emotional discharge), and PTSD and SUD
      symptomatology were measured prior to and at the end of treatment, and at 6- and
      12-month follow-ups. Among the total sample, we found that: (a) avoidant and
      emotional discharge, but not active, coping tended to be positively associated
      with PTSD and SUD symptomatology at baseline; (b) active coping increased and
      avoidant and emotional discharge coping decreased during the 12-month time
      period; and (c) avoidant and emotional discharge, but not active, coping
      longitudinally covaried with PTSD and SUD symptomatology. Results suggest the
      utility of targeting maladaptive coping in treatments for individuals with co
      occurring PTSD and SUD.

PMID- 24854217
TI  - Image-based left ventricular shape analysis for sudden cardiac death risk
      stratification.
AB  - BACKGROUND: Low left ventricular ejection fraction (LVEF), the main criterion
      used in the current clinical practice to stratify sudden cardiac death (SCD)
      risk, has low sensitivity and specificity. OBJECTIVE: To uncover indices of left
      ventricular (LV) shape that differ between patients with a high risk of SCD and
      those with a low risk. METHODS: By using clinical cardiac magnetic resonance
      imaging and computational anatomy tools, a novel computational framework to
      compare 3-dimensional LV endocardial surface curvedness, wall thickness, and
      relative wall thickness between patient groups was implemented. The framework was
      applied to cardiac magnetic resonance data of 61 patients with ischemic
      cardiomyopathy who were selected for prophylactic implantable cardioverter
      defibrillator treatment on the basis of reduced LVEF. The patients were
      classified by outcome: group 0 had no events; group 1, arrhythmic events; and
      group 2, heart failure events. Segmental differences in LV shape were assessed.
      RESULTS: Global LV volumes and mass were similar among groups. Compared with
      patients with no events, patients in groups 1 and 2 had lower mean shape metrics
      in all coronary artery regions, with statistical significance in 9 comparisons,
      reflecting wall thinning and stretching/flattening. CONCLUSION: In patients with
      ischemic cardiomyopathy and low LVEF, there exist quantifiable differences in 3
      dimensional endocardial surface curvedness, LV wall thickness, and LV relative
      wall thickness between those with no clinical events and those with arrhythmic or
      heart failure outcomes, reflecting adverse LV remodeling. This retrospective
      study is a proof of concept to demonstrate that regional LV remodeling indices
      have the potential to improve the personalized risk assessment for SCD.

PMID- 24854220
TI  - Comparison of the influence of humidity and D-mannitol on the organization of
      tetraethylene glycol-terminated self-assembled monolayers and immobilized
      antimicrobial peptides.
AB  - We report the use of polarization-modulation infrared reflection-absorption
      spectroscopy (PM-IRRAS) to characterize the effects of relative humidity (RH) and
      d-mannitol on the conformations of tetraethylene glycol (EG4)-terminated self
      assembled monolayers (SAMs) and immobilized antimicrobial peptides (Cecropin P1
      and a hybrid of Cecropin A (1-8) and Melittin (1-18)). These results are used to
      assess the extent to which d-mannitol can substitute for water in promoting
      conformational states of the SAMs and oligopeptides similar to those induced by
      hydration. Our measurements reveal a red shift of the COC asymmetric stretching
      vibration of the EG4-terminated SAMs with increasing humidity, consistent with a
      transition from a mixed all-trans/helical (7/2 helix) conformation at 0% RH to a
      predominantly helical conformation at 90% RH. Significantly, under dry
      conditions, a thin (2 nm in thickness) overlayer of d-mannitol generated the COC
      spectroscopic signature of the EG4-terminated SAM measured at high humidity.
      Comparisons of the effects of humidity and d-mannitol on the secondary structure
      of the two oligopeptides also revealed both to cause the amide I peak positions,
      which were measured in dry air (and without d-mannitol) to correspond to alpha
      helical conformations, to undergo red-shifts. The magnitudes of the red-shifts,
      however, were more pronounced for dry d-mannitol than for high RH, with Cecropin
      P1 and the hybrid peptide exhibiting amide I peak positions under d-mannitol
      consistent with bulk aqueous solution secondary structures (random and beta
      sheet, respectively). These results are discussed in the context of prior reports
      of the tendency of d-mannitol to form glassy states in the absence of water.
      Overall, the results presented in this paper support the hypothesis that d
      mannitol can substitute, in at least some ways, for the influence of water on the
      conformational states of biologically relevant molecules at interfaces. The
      results provide guidance for the design of interfaces for water-free biologics. 

PMID- 24854219
TI  - Extended-release naltrexone for alcohol and opioid dependence: a meta-analysis of
      healthcare utilization studies.
AB  - Through improved adherence, once-monthly injectable extended-release naltrexone
      (XR-NTX) may provide an advantage over other oral agents approved for alcohol and
      opioid dependence treatment. The objective of this study was to evaluate cost and
      utilization outcomes between XR-NTX and other pharmacotherapies for treatment of
      alcohol and opioid dependence. Published studies were identified through
      comprehensive search of two electronic databases. Studies were included if they
      compared XR-NTX to other approved medicines and reported economic and healthcare
      utilization outcomes in patients with opioid or alcohol dependence. We identified
      five observational studies comparing 1,565 patients using XR-NTX to other
      therapies over 6 months. Alcohol dependent XR-NTX patients had longer medication
      refill persistence versus acamprosate and oral naltrexone. Healthcare utilization
      and costs was generally lower or as low for XR-NTX-treated patients relative to
      other alcohol dependence agents. Opioid dependent XR-NTX patients had lower
      inpatient substance abuse-related utilization versus other agents and $8170 lower
      total cost versus methadone.

PMID- 24854221
TI  - Biodistribution study of free and microencapsulated 6-methylcoumarin in Wistar
      rats by HPLC.
AB  - A sensitive, specific and reproducible HPLC method has been developed and
      validated for the quantitative determination of 6-methylcoumarin (6MC) in plasma
      and other tissues in Wistar rats. A C18 column was used with UV detection at 321
      nm and a gradient system consisting of methanol-deionized water was used as
      mobile phase. The retention time for 6MC was 14.921 min and no interfering peaks
      were observed for any of the matrices. Linear relationships (r(2)  > 0.997) were
      obtained between the peak height ratios and the corresponding biological sample
      concentrations over the range 0.4-12.8 ug/mL. Precision and accuracy were
      evaluated; the coefficient of variation and the relative error for all of the
      organs were <2 and 7%, respectively. The limit of quantitation was 0.20 ug/mL for
      the heart and 0.30 ug/mL for the other tissues evaluated. This HPLC method was
      successfully used in the determination of 6MC in the biodistribution study after
      administration of 200 mg/kg of both 6MC-free and 6MC-loaded polymeric
      microparticles. In this study, extensive 6MC was found, in both free and
      microencapsulated forms, in all the organs tested. The 6MC-free showed a range of
      between 1.7 and 11.5 ug/g, while the microencapsulated 6MC showed concentrations
      of between 6.35 and 17.7 ug/g, suggesting that 6MC improved absorption rate.

PMID- 24854222
TI  - Work experiences of internationally trained pharmacists in Great Britain.
AB  - OBJECTIVES: Internationally trained health professionals are an important part of
      the domestic workforce, but little is known about the working experiences of
      internationally trained pharmacists (ITPs) in Great Britain (GB). The purpose of
      this study is to explore the work experiences of ITPs practising in the community
      or hospital sector in GB. METHODS: Twenty-five semi-structured, face-to-face
      interviews were conducted with a sample of European Economic Area (EEA) and non
      EEA pharmacists who, at the time of the study, practised in the community (n =
      20) or hospital sector (n = 5) in the North West England from March to May 2009.
      KEY FINDINGS: In general, ITPs complained about their heavy workload, long
      working hours and lack of support from their employers. Specifically, EEA
      pharmacists in most cases felt excluded from the professional network and sensed
      colleagues saw them as 'foreigners' while some non-EEA pharmacists had to deal
      with a level of hostility from patients. CONCLUSIONS: This novel research
      provides a foundation for future work on ITPs in GB and could assist employers to
      better target their efforts in development of standards to support the working
      experiences of ITPs in GB.

PMID- 24854223
TI  - Biotransformation of explosives by Reticulitermes flavipes--associated termite
      Endosymbionts.
AB  - BACKGROUND/AIMS: Termites have an important role in the carbon and nitrogen
      cycles despite their reputation as destructive pests. With the assistance of
      microbial endosymbionts, termites are responsible for the conversion of complex
      biopolymers into simple carbon substrates. Termites also rely on endosymbionts
      for fixing and recycling nitrogen. As a result, we hypothesize that termite
      bacterial endosymbionts are a novel source of metabolic pathways for the
      transformation of nitrogen-rich compounds like explosives. METHODS: Explosives
      transformation capability of termite (Reticulitermes flavipes)-derived
      endosymbionts was determined in media containing the chemical constituents
      nitrotriazolone (NTO) and hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) that
      comprise new insensitive explosive formulations. Media dosed with 40 ug/ml of
      explosive was inoculated with surface-sterilized, macerated termites. Bacterial
      isolates capable of explosives transformation were characterized by 16S rRNA
      sequencing. RESULTS: Termite-derived enrichment cultures demonstrated degradation
      activity towards the explosives NTO, RDX, as well as the legacy explosive 2,4,6
      trinitrotoluene (TNT). Three isolates with high similarity to the
      Enterobacteriaceae(Enterobacter, Klebsiella) were able to transform TNT and NTO
      within 2 days, while isolates with high similarity to Serratia marcescens and
      Lactococcus lactis were able to transform RDX. CONCLUSION: Termite endosymbionts
      harbor a range of metabolic activities and possess unique abilities to transform
      nitrogen-rich explosives.

PMID- 24854224
TI  - Strong non-classical induction forces in ion-surface interactions: general origin
      of Hofmeister effects.
AB  - Hofmeister effects continue to defy all-encompassing theories, and their origin
      is still a matter of debate. We observed strong Hofmeister effects in Ca2+/Na+
      exchange on a permanently charged surface over a wide range of ionic strengths.
      They could not be attributed to dispersion forces, classical induction forces,
      ionic size, or hydration effects. We demonstrated that another stronger force was
      active in the ion-surface interactions, and which would create Hofmeister effects
      in general. The strength of this force was up to 10(4) times that of the
      classical induction force, and could be comparable to the Coulomb force. Coulomb,
      dispersion and hydration effects appeared to be interwined to affect the force.
      The presence of the observed strong non-classical induction force implied that
      energies of non-valence electrons of ions/atoms at the interface might be heavily
      underestimated in current theories, and possibly just those underestimated
      energies of non-valence electrons determined Hofmeister effects.

PMID- 24854225
TI  - Loading dynamics of a sliding DNA clamp.
AB  - Sliding DNA clamps are loaded at a ss/dsDNA junction by a clamp loader that
      depends on ATP binding for clamp opening. Sequential ATP hydrolysis results in
      closure of the clamp so that it completely encircles and diffuses on dsDNA. We
      followed events during loading of an E. coli beta clamp in real time by using
      single-molecule FRET (smFRET). Three successive FRET states were retained for 0.3
      s, 0.7 s, and 9 min: Hydrolysis of the first ATP molecule by the gamma clamp
      loader resulted in closure of the clamp in 0.3 s, and after 0.7 s in the closed
      conformation, the clamp was released to diffuse on the dsDNA for at least 9 min.
      An additional single-molecule polarization study revealed that the interfacial
      domain of the clamp rotated in plane by approximately 8 degrees  during clamp
      closure. The single-molecule polarization and FRET studies thus revealed the real
      time dynamics of the ATP-hydrolysis-dependent 3D conformational change of the
      beta clamp during loading at a ss/dsDNA junction. 

PMID- 24854227
TI  - Comparison of risk management strategies between women testing positive for a
      BRCA variant of unknown significance and women with known BRCA deleterious
      mutations.
AB  - PURPOSE: The aim of this article is to describe cancer risk-reducing behaviors of
      women with BRCA variants of unknown significance. METHODS: A retrospective chart
      review from 1995 to 2012 identified women with BRCA mutations in a northern
      California community system. Exclusion criteria included loss of membership/death
      within 1 year of testing, prior ovarian cancer, or bilateral salpingo
      oophorectomy. Primary outcomes were rate of risk-reducing mastectomy and risk
      reducing salpingo-oophorectomy. RESULTS: The mean age of the 69 variant of
      unknown significance carriers was 50 vs. 47 years for the 305 women with a
      deleterious mutation. Women with a variant of unknown significance were followed
      for a median of 69 months. Among women with a variant of unknown significance,
      30% underwent risk-reducing salpingo-oophorectomy and 11% underwent risk-reducing
      mastectomy, as compared with 74 and 44%, respectively, for women with a
      deleterious mutation. Women with a deleterious mutation were more likely to
      undergo surveillance in the first year after testing. The odds ratios are as
      follows: 2.1 for mammogram, 6.0 for magnetic resonance imaging, 7.7 for Ca-125,
      and 5.0 for transvaginal ultrasound. Fifty-six percent of women with a variant of
      unknown significance were reclassified after a median of 39 months, longer than
      the median time to risk-reducing salpingo-oophorectomy (18.6 months) or risk
      reducing mastectomy (20.1 months). CONCLUSION: Uptake of risk-reducing strategies
      among women with a variant of unknown significance is lower than among women with
      a deleterious mutation. Given the prognostic uncertainty and high rate of
      reclassification for women with a variant of unknown significance,
      individualizing counseling and directing efforts toward surveillance,
      chemoprevention, or salpingectomy are recommended.

PMID- 24854226
TI  - Public preferences for the return of research results in genetic research: a
      conjoint analysis.
AB  - PURPOSE: Recent policies specifying criteria about which individual research
      results to return leave considerable discretion to researchers. This study
      investigated the types of results that the public wants when participating in
      genetic research and whether preferences differ based on willingness to
      participate. METHODS: A representative survey of US adults used conjoint analysis
      to measure priorities among eight principles of a results policy for a proposed
      large-cohort study. Policy preferences were measured using 12 tasks in which
      respondents chose between two groupings of the policy principles. Stratified
      analysis compared those self-identified as likely or unlikely to participate in
      genomic research. RESULTS: Of 1,515 respondents, 56% would participate in the
      proposed study. All eight principles were positively endorsed by participants
      (all P < 0.003), with priority placed on providing results at no cost and
      returning well-validated results for treatable and serious diseases. Providing
      detailed result reports was more highly valued than providing staff to explain
      results (P = 0.0005). Receiving results about major changes in risk was
      marginally disvalued by those unlikely to participate (P = 0.35). CONCLUSION:
      Public preferences for well-validated individual research results for serious,
      actionable diseases agree with emerging recommendations. However, because
      preferences for receiving individual research results vary, some choices should
      be offered to research participants.

PMID- 24854228
TI  - Pemphigoid nodularis with diverse IgG, IgA and IgE antibodies showing
      neutrophilic papillary microabscesses.

PMID- 24854230
TI  - A novel 3D inorganic heteropoly blue as visible light responsive photocatalyst.
AB  - A new 3D extended heteropoly blue Ba4[SiW(V)4W(VI)8O40].H2O (1) composed of
      twelve-coordinated alpha-Keggin anions [SiW(V)4W(VI)8O40](8-) and eight
      coordinated Ba sites {BaO8} has been hydrothermally synthesized and fully
      characterized by elemental analysis, IR spectroscopy, XPS, single crystal X-ray
      and X-ray powder (XRPD) diffraction. 1 represents the first inorganic 3D
      framework constructed from four-electron reduced alpha-Keggin anions linked by
      alkaline earth metals. The photocatalytic activity of 1 has been evaluated for
      rhodamine B (RhB) degradation. 1 exhibits excellent catalytic activity for the
      degradation of RhB in the presence of H2O2and the involvement of visible light
      makes a more complete degradation. The results of the current study suggest that
      multi-electron reduced polyoxometalates can catalyze efficient degradation of an
      organic dye with H2O2. 

PMID- 24854229
TI  - Period, birth cohort and prevalence of dementia in mainland China, Hong Kong and
      Taiwan: a meta-analysis.
AB  - OBJECTIVE: There have been dramatic societal changes in East Asia over the last
      hundred years. Several of the established risk factors could have important
      period and cohort effects. This study explores temporal variation of dementia
      prevalence in mainland China, Hong Kong and Taiwan taking study methods into
      account. METHODS: Seventy prevalence studies of dementia in mainland China, Hong
      Kong and Taiwan were identified from 1980 to 2012. Five period groups (before
      1990, 1990 ~ 1994, 1995 ~ 1999, 2000 ~ 2004 and 2005 ~ 2012) and five birth
      cohort groups (1895 ~ 1909, 1910 ~ 1919, 1920 ~ 1929, 1930 ~ 1939 and 1940 ~
      1950) were categorised using the year of investigation and 5-year age groups.
      Pooled prevalence by age, period and birth cohort groups was estimated through
      meta-regression model and meta-analysis taking diagnostic criteria and age
      structure into account. RESULTS: After adjusting for diagnostic criteria, the
      study age range and age structure, the prevalence of dementia in the older
      population aged 60 years and over fluctuated across periods but not reaching
      significance and were estimated as 1.8%, 2.5%, 2.1%, 2.4% and 3.1% for the five
      periods from pre-1990 to 2005 ~ 2012. A potential increasing pattern from less to
      more recent birth cohort groups was found in the major studies using older
      diagnostic criteria with wider differences in the age groups over 70 years.
      CONCLUSIONS: This study found no significant variation across periods but
      suggested a potential cohort effect. The influence of societal changes might
      moderate early life experiences across different generations with substantial
      impact on mental health in older age.

PMID- 24854232
TI  - First experiences with an individual nasal olive in patients with hereditary
      haemorrhagic telangiectasia (HHT).
AB  - Hereditary haemorrhagic teleangiectasia (HHT) is most notably characterized by
      vulnerable vascular formations of the nasal superficial mucosa. Epistaxis is one
      of the most common symptoms of the afflicted patients, with an incidence of more
      than 90 %. A variable series of treatments have been described, ranging from
      nasal ointments to the complete surgical occlusion of the nose. The objective of
      this pilot study is the presentation of first experiences in treating patients
      suffering from HHT and chronically recurrent epistaxis with an individual nasal
      olive made from silicone. Eleven patients (six men, five women) aging from 44 to
      80 years with known HHT were treated at the ENT department of Homburg/Saar
      between October 2008 and July 2012 because of nasal bleeding by Nd:YAG laser or
      argon plasma coagulation. After the surgical treatment, an imprint of the nasal
      aditus was taken to manufacture an individual custom-made silicone nasal olive.
      Patients were wearing the nasal olive for 3-8 h a day. Check-ups were made every
      6 months. Epistaxis severity score (ESS) was used pre- and post-nasal olive
      application. The observation period was 12-48 months. The utilization of the
      silicone nasal olive led to a distinct reduction of epistaxis events. Apart from
      the nasal olive, our patients needed no further treatment of the nose during the
      observation period except for a nasal ointment. Insertion and removal of the
      nasal olive were handled by the patients themselves. The local manipulation in
      handling the nasal olive caused no epistaxis itself. A significant improvement of
      the ESS and satisfaction was reported in all patients. Use of an individually
      manufactured silicone nasal olive is a promising extension to the established
      treatments of epistaxis in HHT patients. Tolerance towards this treatment by the
      patients was high due to the low personal burden and encumbrance. The extended
      use of the presented method in HHT patients may be beneficial. However, a more
      prolonged observation period is necessary in the future to judge the long-term
      efficiency of individual nasal olives.

PMID- 24854231
TI  - Pyriform sinus squamous cell carcinoma: oncological outcomes in good responders
      of induction chemotherapy-based larynx preservation protocols.
AB  - Induction chemotherapy-based larynx preservation protocols use chemotherapy to
      select exclusively patients with 'chemosensitive' tumors for a nonsurgical
      treatment with radiation therapy. This study on pyriform sinus squamous cell
      carcinoma (SCC) is interested in the oncological outcome of treatment based on
      radiation therapy when offered to patients with tumors responding to induction
      chemotherapy. This was a retrospective cohort study. The cohort included good
      responders to induction chemotherapy, subsequently treated with definite
      radiation therapy (with or without concomitant chemotherapy) for pyriform sinus
      SCC, in a tertiary referral cancer center. The primary endpoints were overall,
      laryngectomy-free and disease-free survival and the secondary endpoints were
      analysis of treatment failures and possibilities of salvage treatment. Forty-two
      patients fulfilled the inclusion criteria and were retained for analysis; 7% were
      stage II (3/42), 48% stage III (20/42) and 45% stage IV (19/42). At 1, 3 and 5
      years, the overall survival was 95% (40/42), 74% (31/42), and 60% (SE ~ 0.08),
      respectively. For the same intervals, the laryngectomy-free survival was 90%
      (38/42), 69% (29/42) and 50% (SE ~ 0.08), respectively. The estimated 5-year
      disease-free survival was also 50%. Disease-free survival was significantly
      better for N0 patients. There was a 28% recurrence rate, mainly in the primary
      tumor site (9/11), with or without simultaneous nodal recurrence. Interestingly,
      more than one-third of all oncologic failures occurred beyond the first 3 years
      of follow-up. Salvage treatment was not possible or definitely inefficient in at
      least 2/3 of all recurrences. In candidates for larynx preservation for a
      pyriform sinus SCC, good response to induction chemotherapy followed by definite
      radiation therapy seems to be associated with a more favorable prognosis.
      Nevertheless, in case of locoregional recurrence the possibilities for efficient
      salvage treatment are limited.

PMID- 24854233
TI  - Spontaneous calcium transients manifest in the regenerating muscle and are
      necessary for skeletal muscle replenishment.
AB  - Tissue regeneration entails replenishing of damaged cells, appropriate cell
      differentiation and inclusion of regenerated cells into functioning tissues. In
      adult humans, the capacity of the injured spinal cord and muscle to self-repair
      is limited. In contrast, the amphibian larva can regenerate its tail after
      amputation with complete recovery of muscle, notochord and spinal cord. The
      cellular and molecular mechanisms underlying this phenomenon are still unclear.
      Here we show that upon injury muscle cell precursors exhibit Ca(2+) transients
      that depend on Ca(2+) release from ryanodine receptor-operated stores. Blockade
      of these transients impairs muscle regeneration. Furthermore, inhibiting Ca(2+)
      transients in the regenerating tail prevents the activation and proliferation of
      muscle satellite cells, which results in deficient muscle replenishment. These
      findings suggest that Ca(2+)-mediated activity is critical for the early stages
      of muscle regeneration, which may lead to developing effective therapies for
      tissue repair. 

PMID- 24854236
TI  - A feasibility study of wearable activity monitors for pre-adolescent school-age
      children.
AB  - INTRODUCTION: Understanding physical activity is key in the fight against
      childhood obesity. The objective of this study was to examine the feasibility of
      using certain wearable devices to measure physical activity among children.
      METHODS: A qualitative study was conducted with 25 children aged 7 to 10 years to
      assess acceptability and compliance of wearable activity devices in this age
      group. During March through August 2012, children participated in a 4-week study
      of 3 accelerometer models and a heart rate monitor. Children were asked to use a
      different device each week for 7 consecutive days. Children and their parents
      completed structured interviews after using each device; they also completed a
      final exit interview. RESULTS: The wrist-worn Polar Active was the device most
      preferred by children and was associated with the highest level of compliance.
      Devices that are comfortable to wear, fit properly, have engaging features, and
      are waterproof increase feasibility and are associated with higher levels of
      compliance. CONCLUSION: The wrist-worn device was the most feasible for measuring
      physical activity among children aged 7 to 10 years. These findings will inform
      researchers in selecting tools for measuring children's physical activity.

PMID- 24854234
TI  - Electrical coupling between the human serotonin transporter and voltage-gated
      Ca(2+) channels.
AB  - Monoamine transporters have been implicated in dopamine or serotonin release in
      response to abused drugs such as methamphetamine or ecstasy (MDMA). In addition,
      monoamine transporters show substrate-induced inward currents that may modulate
      excitability and Ca(2+) mobilization, which could also contribute to
      neurotransmitter release. How monoamine transporters modulate Ca(2+) permeability
      is currently unknown. We investigate the functional interaction between the human
      serotonin transporter (hSERT) and voltage-gated Ca(2+) channels (CaV). We
      introduce an excitable expression system consisting of cultured muscle cells
      genetically engineered to express hSERT. Both 5HT and S(+)MDMA depolarize these
      cells and activate the excitation-contraction (EC)-coupling mechanism. However,
      hSERT substrates fail to activate EC-coupling in CaV1.1-null muscle cells, thus
      implicating Ca(2+) channels. CaV1.3 and CaV2.2 channels are natively expressed in
      neurons. When these channels are co-expressed with hSERT in HEK293T cells, only
      cells expressing the lower-threshold L-type CaV1.3 channel show Ca(2+) transients
      evoked by 5HT or S(+)MDMA. In addition, the electrical coupling between hSERT and
      CaV1.3 takes place at physiological 5HT concentrations. The electrical coupling
      between monoamine neurotransmitter transporters and Ca(2+) channels such as
      CaV1.3 is a novel mechanism by which endogenous substrates (neurotransmitters) or
      exogenous substrates (like ecstasy) could modulate Ca(2+)-driven signals in
      excitable cells. 

PMID- 24854237
TI  - Habitual khat and concurrent khat and tobacco use are associated with subjective
      sleep quality.
AB  - INTRODUCTION: Khat (Catha edulis) is widely used in East Africa and the Middle
      East, often in combination with tobacco smoking. Sleep disturbance has been
      linked with habitual khat use; however, no systematic attempt has been made to
      test the hypothesis that use of khat and khat and tobacco in combination are
      related to sleep disturbance. Sleep disturbances are associated with
      dysregulations in emotional and physiological functions and can increase health
      risks. METHODS: We developed and used the Arabic version of the Pittsburgh Sleep
      Quality Index (PSQI) to conduct a cross-sectional study in Yemen examining
      subjective sleep quality in 151 concurrent users of khat and tobacco, 141 khat
      only users, and 92 nonusers. Measures on subjective mood were also collected. A
      series of analyses of variance and chi(2) tests were conducted to test whether
      khat and tobacco use was linked with sleep disturbances. RESULTS: Concurrent
      users of tobacco and khat and khat-only users showed greater sleep disturbances
      than nonusers as assessed by the PSQI global scores (all P values < .001) and
      component scores. PSQI scores were correlated with negative and positive mood
      (all P values < .004). CONCLUSION: Sleep disturbances may be 1 mechanism of the
      link between khat, tobacco, and negative health outcomes. Our findings may be
      useful in developing targeted prevention and harm-reduction strategies to
      minimize health care burdens associated with these substances. Our study also
      provides initial support for the Arabic version of PSQI.

PMID- 24854235
TI  - Cholinergic transmission during nicotine withdrawal is influenced by age and pre
      exposure to nicotine: implications for teenage smoking.
AB  - Adolescence is a unique period of development characterized by enhanced tobacco
      use and long-term vulnerability to neurochemical changes produced by adolescent
      nicotine exposure. In order to understand the underlying mechanisms that
      contribute to developmental differences in tobacco use, this study compared
      changes in cholinergic transmission during nicotine exposure and withdrawal in
      naive adult rats compared to (1) adolescent rats and (2) adult rats that were pre
      exposed to nicotine during adolescence. The first study compared extracellular
      levels of acetylcholine (ACh) in the nucleus accumbens (NAc) during nicotine
      exposure and precipitated withdrawal using microdialysis procedures. Adolescent
      (postnatal day, PND, 28-42) and adult rats (PND60-74) were prepared with osmotic
      pumps that delivered nicotine for 14 days (adolescents 4.7 mg/kg/day; adults 3.2
      mg/kg/day; expressed as base). Another group of adults was exposed to nicotine
      during adolescence and then again in adulthood (pre-exposed adults) using similar
      methods. Control rats received a sham surgery. Following 13 days of nicotine
      exposure, the rats were implanted with microdialysis probes in the NAc. The
      following day, dialysis samples were collected during baseline and following
      systemic administration of the nicotinic receptor antagonist mecamylamine (1.5
      and 3.0 mg/kg, i.p.) to precipitate withdrawal. A second study compared various
      metabolic differences in cholinergic transmission using the same treatment
      procedures as the first study. Following 14 days of nicotine exposure, the NAc
      was dissected and acetylcholinesterase (AChE) activity was compared across
      groups. In order to examine potential group differences in nicotine metabolism,
      blood plasma levels of cotinine (a nicotine metabolite) were also compared
      following 14 days of nicotine exposure. The results from the first study revealed
      that nicotine exposure increased baseline ACh levels to a greater extent in
      adolescent versus adult rats. During nicotine withdrawal, ACh levels in the NAc
      were increased in a similar manner in adolescent versus adult rats. However, the
      increase in ACh that was observed in adult rats experiencing nicotine withdrawal
      was blunted in pre-exposed adults. These neurochemical effects do not appear to
      be related to nicotine metabolism, as plasma cotinine levels were similar across
      all groups. The second study revealed that nicotine exposure increased AChE
      activity in the NAc to a greater extent in adolescent versus adult rats. There
      was no difference in AChE activity in pre-exposed versus naive adult rats. In
      conclusion, our results suggest that nicotine exposure during adolescence
      enhances baseline ACh in the NAc. However, the finding that ACh levels were
      similar during withdrawal in adolescent and adult rats suggests that the enhanced
      vulnerability to tobacco use during adolescence is not related to age differences
      in withdrawal-induced increases in cholinergic transmission. Our results also
      suggest that exposure to nicotine during adolescence suppresses withdrawal
      induced increases in cholinergic responses during withdrawal. Taken together,
      this report illustrates important short- and long-term changes within cholinergic
      systems that may contribute to the enhanced susceptibility to tobacco use during
      adolescence.

PMID- 24854238
TI  - Comparing farmers' market revenue trends before and after the implementation of a
      monetary incentive for recipients of food assistance.
AB  - INTRODUCTION: We examined the influence of an intervention to increase fruit and
      vegetable purchases at farmers' markets for recipients of food assistance, Shop N
      Save (SNS), on revenue trends at a farmers' market located at a federally
      qualified health center (FQHC) in rural South Carolina. We compared revenue
      trends for 20 weeks before the intervention (2011) and 20 weeks after (2012).
      METHODS: SNS provided one $5 monetary incentive per week to customers spending $5
      or more in food assistance at the farmers' market. SNS was available to any
      farmers' market customer using Supplemental Nutrition Assistance Program (SNAP),
      Special Supplemental Nutrition Program for Women, Infants, and Children (WIC),
      and/or Senior or WIC Farmers' Market Nutrition Program (FMNP) vouchers. Sales
      receipts were recorded for each transaction at the farmers' market to document
      payment type and the cost of the purchase. All SNS participants completed a one
      time enrollment survey. RESULTS: A total of 336 customers self-enrolled in SNS
      from June through October 2012. Most SNS participants were female, African
      American, and patients at the FQHC. In total, the use of all forms of food
      assistance (SNAP, WIC, and FMNP) at the farmers' market increased significantly
      after the intervention (from 10% before, to 25% after, P = .003). Senior FMNP
      vouchers and SNAP usage increased the most. CONCLUSION: Interventions that
      provide incentives to recipients of food assistance programs at farmers' markets
      are a viable strategy for increasing food assistance usage and revenue.

PMID- 24854240
TI  - Microarray-based gene expression profiling suggests adaptation of lung epithelial
      cells subjected to chronic cyclic strain.
AB  - BACKGROUND/AIMS: Mechanical strain of the lung tissue is a physiological process
      that affects the behavior of lung cells. Since recent evidence also suggests
      alterations in the expression of certain genes as a consequence of
      mechanotransduction, our study aimed at the analysis of the gene expression
      profile in lung epithelial cells subjected to chronic cyclic strain. METHODS:
      Various human lung epithelial cell lines (A549 as principal adherent cell line
      and four others) were subjected to cyclic strain (16 % surface distension, 12
      min(-1)) in a Strain Cell Culture Device for 24 h. In comparison to static
      controls, expression analyses were performed by gene microarray and qPCR.
      RESULTS: Microarray analysis revealed many differences in the gene expression but
      at moderate levels. Altogether 25 genes were moderately down-regulated (0.86-fold
      +/- 0.06) and 26 genes were up-regulated (1.18-fold +/- 0.10) in A549 and the
      others. Strain-regulated genes often code for transcription factors, such as E2F4
      and SRF. qPCR analyses confirmed the up-regulation of both transcription factors
      and further genes, such as PLAU (urokinase-type plasminogen activator) and S100A4
      (S100 protein A4). Moreover, we showed the down-regulations of AGR2 (anterior
      gradient 2) and LCN2 (lipocalin 2). CONCLUSIONS: We identified many genes of
      which the expression was moderately altered in lung epithelial cells subjected to
      chronic cyclic strain. Although many moderate changes in the gene expression
      profile might affect cellular behavior, it also suggests an effective adaptation
      of cells to mechanical forces in long-term conditions.

PMID- 24854241
TI  - Effect of morphology of nanoscale hydrated channels on proton conductivity in
      block copolymer electrolyte membranes.
AB  - Hydrated membranes with cocontinuous hydrophilic and hydrophobic phases are
      needed to transport protons in hydrogen fuel cells. Herein we study the water
      uptake and proton conductivity of a model fuel cell membrane comprising a
      triblock copolymer, polystyrenesulfonate-block-polyethylene-block
      polystyrenesulfonate (S-SES), as a function of water activity in both humid air
      and liquid water. We demonstrate that the water uptake and proton conductivity of
      S-SES membranes equilibrated in liquid water are fundamentally different from
      values obtained when they were equilibrated in humid air. The morphological
      underpinnings of our observations were determined by synchrotron small-angle X
      ray scattering and cryogenic scanning transmission electron microscopy. A
      discontinuous increase in conductivity when nearly saturated humid air is
      replaced with liquid water coincides with the emergence of heterogeneity in the
      hydrated channels: a water-rich layer is sandwiched between two polymer-rich
      brushes. While the possibility of obtaining heterogeneous hydrated channels in
      polymer electrolyte membranes has been discussed extensively, to our knowledge,
      this is the first time that direct evidence for the formation of water-rich
      subdomains is presented. 

PMID- 24854239
TI  - Hypertension prevalence, awareness, treatment, and control and sodium intake in
      Shandong Province, China: baseline results from Shandong-Ministry of Health
      Action on Salt Reduction and Hypertension (SMASH), 2011.
AB  - INTRODUCTION: In China, population-based blood pressure levels and prevalence of
      hypertension are increasing. Meanwhile, sodium intake, a major risk factor for
      hypertension, is high. In 2011, to develop intervention priorities for a salt
      reduction and hypertension control project in Shandong Province (population 96
      million), a cross-sectional survey was conducted to collect information on sodium
      intake and hypertension prevalence, awareness, treatment, and control. METHODS:
      Complex, multistage sampling methods were used to select a provincial
      representative adult sample. Blood pressure was measured and a survey conducted
      among all participants; condiments were weighed in the household, a 24-hour
      dietary recall was conducted, and urine was collected. Hypertension was
      determined by blood pressure measured on a single occasion and self-reported use
      of antihypertension medications. RESULTS: Overall, 23.4% (95% confidence interval
      [CI], 20.9%-26.0%) of adults in Shandong were estimated to have hypertension.
      Among those classified as having hypertension, approximately one-third (34.5%)
      reported having hypertension, approximately one-fourth (27.5%) reported taking
      medications, and one-seventh (14.9%) had their blood pressure controlled
      (<140/<90 mm Hg). Estimated total average daily dietary sodium intake was 5,745
      mg (95% CI, 5,428 mg-6,063 mg). Most dietary sodium (80.8%) came from salt and
      high-salt condiments added during cooking: a sodium intake of 4,640 mg (95% CI,
      4,360 mg-4,920 mg). The average daily urinary sodium excretion was 5,398 mg (95%
      CI, 5,112 mg-5,683 mg). CONCLUSION: Hypertension and excessive sodium intake in
      adults are major public health problems in Shandong Province, China.

PMID- 24854242
TI  - Transition-metal-free oxidative carboazidation of acrylamides via cascade C-N and
      C-C bond-forming reactions.
AB  - A novel transition-metal-free oxidative carboazidation of acrylamides using
      inexpensive NaN3 and K2S2O8 was achieved, which not only provided an efficient
      method to prepare various N3-substituted oxindoles, but also represented a novel
      strategy for C-N and C-C bond formation via a free-radical cascade process. This
      transformation exhibits excellent functional group tolerance, affording the
      desired oxindoles in good to excellent yields. 

PMID- 24854244
TI  - Transforming growth factor-Beta inhibits heme oxygenase-1 expression in lung
      fibroblast through nuclear factor-kappa-B-dependent pathway.
AB  - BACKGROUND: Heme oxygenase-1 (HO-1) contributes to the pathogenesis of pulmonary
      fibrosis. However, the expression of HO-1 in fibroblasts under fibrotic
      conditions has not been studied. METHODS: This study was conducted to investigate
      the expression of HO-1 in lung fibroblasts from mice and humans under fibrotic
      conditions by Western blot. RESULTS: We found that the expression of HO-1 was
      significantly decreased in lung fibroblasts isolated from bleomycin-challenged
      mice in comparison with control mice. Transforming growth factor-beta (TGF-beta)
      inhibited HO-1 expression and induced differentiation in human lung fibroblasts.
      Pretreatment with nuclear factor-kappaB (NF-kappaB) activation inhibitor or
      knockdown of the NF-kappaB p65 subunit attenuated TGF-beta-induced inhibition of
      HO-1 expression and differentiation in human lung fibroblasts. Similarly,
      lysophosphatidic acid (LPA) induced TGF-beta expression and decreased HO-1
      expression in human lung fibroblasts. Interestingly, pretreatment with
      neutralized anti-TGF-beta antibody attenuated LPA effects in human lung
      fibroblasts. CONCLUSION: These data suggested that TGF-beta inhibited HO-1
      expression in human lung fibroblasts through activation of NF-kappaB.

PMID- 24854246
TI  - Metal-mediated transformations of small molecules.

PMID- 24854243
TI  - Hyperplastic discs differentially regulates the transcriptional outputs of
      hedgehog signaling.
AB  - Hedgehog (Hh) acts as a morphogen to activate the transcription of diverse target
      genes via its downstream effector Cubitus interruptus (Ci). Currently, it is less
      understood how Ci recruits co-factors to activate transcription. Here we report
      that hyperplastic discs (hyd), an E3 ubiquitin ligase, can differentially
      regulate the transcriptional outputs of Hh signaling. We show that loss of Hyd
      activity caused upregulation of some, but not all of Hh target genes.
      Importantly, Hyd does not affect the stability of Ci. Our data suggest that Hyd
      differentially restrains the transcriptional activity of Ci via selective
      association with respective promoters. 

PMID- 24854245
TI  - Incorporation of pyrene in polypyrrole/polystyrene magnetic beads.
AB  - Pyrene, a fluorescent dye, was incorporated into polystyrene particles coated
      with polypyrrole. The incorporation was achieved by treating the
      polypyrrole/polystyrene (PPy/PS) beads in a tetrahydrofuran (THF) solution of the
      pyrene fluorophore followed by rinsing with methanol. The polystyrene cores of
      the beads swell in THF, allowing penetration of pyrene molecules into the
      polystyrene structure. The addition of methanol causes contraction of the swollen
      polystyrene, which encapsulates the dye molecules inside the beads. It is shown
      that the polypyrrole coating is permeable with respect to both the dye and the
      solvent, allowing the transport of molecules between the polystyrene cores and
      the contacting solution. The polypyrrole adlayer can be used as a matrix for the
      incorporation of magnetic nanoparticles. Embedded particles provide magnetic
      functionality to the PPy/PS beads. It is demonstrated that the pyrene-loaded
      beads can be manipulated with an external magnetic field. 

PMID- 24854247
TI  - We are all animals.

PMID- 24854248
TI  - Anthropogenic land use change and infectious diseases: a review of the evidence.
AB  - Humans have altered ecosystems worldwide, and it is important to understand how
      this land use change impacts infectious disease transmission in humans and
      animals. We conducted a systematic review 305 scientific articles investigating
      how specific types of anthropogenic land use change influence infectious disease
      dynamics. We summarized findings, highlighted common themes, and drew attention
      to neglected areas of research. There was an increase in publications on this
      topic over the last 30 years spanning diseases of humans, livestock, and
      wildlife, including a large number of zoonotic pathogens. Most papers (66.9%)
      were observational, 30.8% were review or concept papers, and few studies (2.3%)
      were experimental in nature, with most studies focusing on vector-borne and/or
      multi-host pathogens. Common land use change types related to disease
      transmission were deforestation/forest fragmentation/habitat fragmentation,
      agricultural development/irrigation, and urbanization/suburbanization. In
      response to anthropogenic change, more than half of the studies (56.9%)
      documented increased pathogen transmission, 10.4% of studies observed decreased
      pathogen transmission, 30.4% had variable and complex pathogen responses, and
      2.4% showed no detectable changes. Commonly reported mechanisms by which land use
      change altered infectious disease transmission included alteration of the vector,
      host, and pathogen niche, changes in host and vector community composition,
      changes in behavior or movement of vectors and/or hosts, altered spatial
      distribution of hosts and/or vectors, and socioeconomic factors, and
      environmental contamination. We discussed observed patterns in the literature and
      make suggestions for future research directions, emphasizing the importance of
      ecological and evolutionary theory to understand pathogen responses in changing
      landscapes.

PMID- 24854249
TI  - Trial-based economic evaluations in occupational health: principles, methods, and
      recommendations.
AB  - To allocate available resources as efficiently as possible, decision makers need
      information on the relative economic merits of occupational health and safety
      (OHS) interventions. Economic evaluations can provide this information by
      comparing the costs and consequences of alternatives. Nevertheless, only a few of
      the studies that consider the effectiveness of OHS interventions take the extra
      step of considering their resource implications. Moreover, the methodological
      quality of those that do is generally poor. Therefore, this study aims to help
      occupational health researchers conduct high-quality trial-based economic
      evaluations by discussing the theory and methodology that underlie them, and by
      providing recommendations for good practice regarding their design, analysis, and
      reporting. This study also helps consumers of this literature with understanding
      and critically appraising trial-based economic evaluations of OHS interventions. 

PMID- 24854250
TI  - Prenatal exposure to air toxics and risk of Wilms' tumor in 0- to 5-year-old
      children.
AB  - OBJECTIVE: To study prenatal air toxic exposure and Wilms' tumor in children.
      METHODS: We identified 337 Wilms' tumor cases among children younger than 6 years
      (1988 to 2008) from the California Cancer Registry, randomly selected 96,514
      controls from California birth rolls in 20:1 ratio matched to all cancer cases,
      then linked birth addresses to air monitors within 15 miles to assess exposures.
      Multiple logistic regressions were applied to estimate effects. RESULTS: Children
      prenatally exposed to formaldehyde, polycyclic aromatic hydrocarbons,
      perchloroethylene, or acetaldehyde in the third trimester had an increased odds
      of Wilms' tumor per interquartile increase in concentration (odds ratio [95%
      confidence interval]: 1.28 [1.12 to 1.45], 1.10 [0.99 to 1.22], 1.09 [1.00 to
      1.18], 1.25 [1.07 to 1.45], respectively). CONCLUSIONS: We found positive
      associations for four air toxics. This is the first study of this kind. Future
      studies are needed to confirm our findings.

PMID- 24854252
TI  - Is sickness presenteeism a risk factor for depression? A Danish 2-year follow-up
      study.
AB  - OBJECTIVE: To examine the prospective association between sickness presenteeism
      (SP), that is, working while ill, and the onset of depression. METHODS: We
      carried out a two-wave (2006 to 2008) questionnaire-based study among 1271
      employees from 60 Danish workplaces. Sickness presenteeism was assessed by asking
      participants to report the number of days that they went to work despite illness
      in the preceding year. RESULTS: Multivariate logistic regression revealed that,
      after controlling for several health-related variables and other relevant
      confounders, reporting 8 or more days of SP was associated with an increased risk
      of depression among initially nondepressed participants (odds ratio, 2.45; 95%
      confidence interval, 1.06 to 5.64). No significant sex-related differences were
      observed in this relationship. CONCLUSION: Adding to previous evidence on the
      health effects of SP, this study suggests that working while ill may also be a
      significant risk factor for the development of depression.

PMID- 24854251
TI  - Natural history of upper extremity musculoskeletal symptoms and resulting work
      limitations over 3 years in a newly hired working population.
AB  - OBJECTIVE: To describe the proportions of workers with upper extremity (UE)
      symptoms and work limitations because of symptoms in a newly hired working
      population over a 3-year study period and to describe transitions between various
      outcome states. METHODS: A total of 827 subjects completed repeat self-reported
      questionnaires including demographics, medical and work history, symptoms, and
      work status. Outcomes of interest were UE symptoms and work limitations because
      of symptoms. RESULTS: Up to 72% of workers reported symptoms at least once during
      the study, with 12% reporting persistent symptoms and 27% reporting fluctuating
      symptoms; 31% reported work limitations at least once, with 3% reporting
      consistent work limitations and 8% reporting fluctuating limitations.
      CONCLUSIONS: UE symptoms and work limitations are common among workers and
      dynamic in their course. A better understanding of the natural course of symptoms
      is necessary for targeted interventions.

PMID- 24854253
TI  - Tracking low back problems in a major self-insured workforce: toward improvement
      in the patient's journey.
AB  - OBJECTIVE: To assess the cost outcomes of treatment approaches to care for back
      problems in a major self-insured workforce, using published guidelines to focus
      on low back pain. METHODS: Longitudinally tracked episodes of three types of
      International Classification of Diseases, Ninth Revision diagnosis code
      identified back problems (n=14,787) during 2001 to 2009. Identified five patterns
      of care on the basis of the first 6 weeks of claims and compared their total
      costs per episode with tests that included splits by episode type and duration,
      use of guidelines, and propensity-derived adjustments. RESULTS: Care congruent
      with 10 of 11 guidelines was linked to lower total costs. Of the five patterns,
      complex medical management and chiropractic reported the highest and lowest
      rates, respectively, of guideline-incongruent use of imaging, surgeries, and
      medications, and the highest and lowest total costs. CONCLUSIONS: Approaches
      marked by higher resource utilization and lower guideline congruence are linked
      to greater low back pain total costs. Total cost is a needed input for guideline
      development.

PMID- 24854254
TI  - Physical assaults among education workers: findings from a statewide study.
AB  - OBJECTIVE: Enumerate and describe physical assaults occurring to Pennsylvania
      education workers. METHODS: A cross-sectional survey was mailed to a random
      sample of 6450 workers, stratified on gender, occupation, and region. Logistic
      regression was used to examine risk factors for physical assault. RESULTS: During
      the 2009-2010 school year, 309 of 2514 workers were assaulted 597 times. Special
      education teachers, urban workers, and those in their first 3 years of employment
      were at an increased risk. Most assaults did not lead to medical care or time
      away from work; however, those assaulted were significantly more likely to find
      work stressful, have low job satisfaction, and consider leaving the education
      field (adjusted odds ratio [AOR]=2.5 [95% CI=1.5 to 4.1]; AOR=2.4 [95% CI=1.5 to
      3.9]; AOR=10.7 [95% CI=4.1 to 28.1]). CONCLUSIONS: Although education workers
      experienced few serious physical assaults, the impact of this violence was
      considerable.

PMID- 24854255
TI  - Estimating the net benefit of a specialized return-to-work program for workers on
      short-term disability related to a mental disorder: an example exploring
      investment in collaborative care.
AB  - OBJECTIVE: This article estimates the net benefit for a company incorporating a
      collaborative care model into its return-to-work program for workers on short
      term disability related to a mental disorder. METHODS: Employing a simple
      decision model, the net benefit and uncertainty were explored. RESULTS: The
      breakeven point occurs when the average short-term disability episode is reduced
      by at least 7 days. In addition, 85% of the time, benefits could outweigh costs.
      CONCLUSIONS: Model results and sensitivity analyses indicate that organizational
      benefits can be greater than the costs of incorporating a collaborative care
      model into a return-to-work program for workers on short-term disability related
      to a mental disorder. The results also demonstrate how the probability of a
      program's effectiveness and the magnitude of its effectiveness are key factors
      that determine whether the benefits of a program outweigh its costs.

PMID- 24854256
TI  - Predicting temporal trends in total absenteeism rates for civil service employees
      of a federal public health agency.
AB  - OBJECTIVE: This study evaluates the predictability in temporal absences trends
      due to all causes (total absenteeism) among employees at a federal agency. The
      objective is to determine how leave trends vary within the year, and determine
      whether trends are predictable. METHODS: Ten years of absenteeism data from an
      attendance system were analyzed for rates of total absence. RESULTS: Trends over
      a 10-year period followed predictable and regular patterns during a given year
      that correspond to major holiday periods. Temporal trends in leave among small,
      medium, and large facilities compared favorably with the agency as a whole.
      CONCLUSIONS: Temporal trends in total absenteeism rates for an organization can
      be determined using its attendance system. The ability to predict employee
      absenteeism rates can be extremely helpful for management in optimizing business
      performance and ensuring that an organization meets its mission.

PMID- 24854257
TI  - Effectiveness of a health promotion program among employees in a western United
      States school district.
AB  - OBJECTIVES: To evaluate the effectiveness of a worksite wellness program in
      decreasing health risk. METHODS: Analyses were based on 2411 employees from a
      school district in the western United States that participated in the WellSteps
      wellness program for 12 months. RESULTS: The numbers of high-risk employees at
      baseline were 683 for body mass index, 360 for systolic blood pressure, 242 for
      diastolic blood pressure, 72 for blood glucose, and 216 for total cholesterol.
      Among participants, 46.0% lowered body mass index, 34.7% lowered systolic blood
      pressure, 56.3% lowered diastolic blood pressure, 65.6% lowered blood glucose,
      and 38.6% lowered total cholesterol. The percentages moving out of the high-risk
      categories after 1 year were 11.6%, 39.4%, 70.7%, 38.9%, and 40.7%, respectively.
      CONCLUSIONS: The worksite wellness program effectively lowered risk measures
      among those identified in high-risk categories at baseline.

PMID- 24854258
TI  - Workplace health promotion: what public-sector employees want, need, and are
      ready to change.
AB  - OBJECTIVE: To examine whether employees selected appropriate health change
      targets (HCTs) compared with self-reported lifestyle factors (smoking, nutrition,
      alcohol, physical activity [PA], sedentariness, weight status, and psychological
      distress) and readiness to change their HCT. METHODS: Cross-sectional data of
      3367 state-government employees from Tasmania, Australia, were collected in 2010.
      RESULTS: Overall, respondents chose HCTs relevant to their health behaviors. The
      most frequently selected HCTs were PA, diet, and weight. The majority was in the
      "action" stage for their HCT, except for those nominating smoking cessation,
      changes to work characteristics, and moderating alcohol intake. CONCLUSIONS:
      Employee perceptions of their own health needs broadly corresponded to their
      health-related behaviors, weight status, and stress. Workplace health
      facilitators should be prepared for variable uptake on smoking cessation
      programs. Physical activity interventions are likely well received, irrespective
      of risk-related lifestyle factors.

PMID- 24854260
TI  - Adiposity predicts self-reported frequency of poor health days among male
      firefighters.
AB  - OBJECTIVE: Quantify the association between adiposity and frequency of self
      reported poor health days among male firefighters. METHODS: Measures were taken
      for body mass index, waist circumference, and percentage of body fat.
      Firefighters self-reported the outcome of the number of poor health days in the
      past 30 days. Zero-inflated negative binomial models and fractional polynomial
      plots were used to determine the impact of adiposity on the frequency of self
      reported poor health days. RESULTS: Body mass index (rate ratio [RR]: 1.037; 95%
      confidence interval [CI]: 1.003 to 1.073), waist circumference (RR: 1.012; 95%
      CI: 0.999 to 1.030), and percentage of body fat (RR: 1.021; 95% CI: 0.999 to
      1.041) were associated with self-reported poor health days. CONCLUSIONS:
      Adiposity is positively associated with frequency of self-reported poor health
      days among male firefighters. Future efforts to improve health among firefighters
      should emphasize reductions in adiposity.

PMID- 24854261
TI  - Biological effects of emissions from resistance spot welding of zinc-coated
      material after controlled exposure of healthy human subjects.
AB  - OBJECTIVE: Do emissions from a resistance spot welding process of zinc-coated
      materials induce systemic inflammation in healthy subjects after exposure for 6
      hours? METHODS: Twelve healthy male subjects were exposed once for 6 hours either
      to filtered ambient air or to welding fume from resistance spot welding of zinc
      coated material (mass concentration approximately 100 MUg m). Biological effects
      were measured before, after, and 24 hours after exposure. RESULTS: At the
      concentrations used in this study, however, the suspected properties of ultrafine
      particles did not lead to systemic inflammation as reflected by high-sensitivity
      C-reactive protein or other endpoint parameters under consideration. CONCLUSIONS:
      Ultrafine particles from a resistance spot welding process of zinc-covered
      materials with a number concentration of about 10 cm and a mass concentration of
      about 100 MUg m did not induce systemic inflammation.

PMID- 24854262
TI  - In Memoriam: Patricia A. Buffler, PhD, MPH, CPH 1938-2013.

PMID- 24854259
TI  - A dose-response study of arsenic exposure and markers of oxidative damage in
      Bangladesh.
AB  - OBJECTIVE: To evaluate the dose-response relationship between arsenic (As)
      exposure and markers of oxidative damage in Bangladeshi adults. METHODS: We
      recruited 378 participants drinking water from wells assigned to five water As
      exposure categories; the distribution of subjects was as follows: (1) less than
      10 MUg/L (n=76); (2) 10 to 100 MUg/L (n=104); (3) 101 to 200 MUg/L (n=86); (4)
      201 to 300 MUg/L (n=67); and (5) more than 300 MUg/L (n=45). Arsenic
      concentrations were measured in well water, as well as in urine and blood.
      Urinary 8-oxo-2'-deoxyguanosine and plasma protein carbonyls were measured to
      assess oxidative damage. RESULTS: None of our measures of As exposure were
      significantly associated with protein carbonyl or 8-oxo-2'-deoxyguanosine levels.
      CONCLUSIONS: We found no evidence to support a significant relationship between
      long-term exposure to As-contaminated drinking water and biomarkers of oxidative
      damage among Bangladeshi adults.

PMID- 24854263
TI  - Systematic review and meta-analysis on management of hemodialysis catheter
      related bacteremia.
AB  - Hemodialysis catheter-related bacteremia is a common clinical problem with
      several management options. We performed a systematic review and meta-analysis to
      determine cure proportions with systemic antibiotics, antibiotic lock solution,
      and guidewire exchange. We searched databases and registries; conference
      proceedings from relevant medical societies; and article reference lists. Data
      regarding management approach, cure, follow-up, recurrence, complications, and
      microbiology were abstracted and pooled from 28 selected publications. Odds
      ratios (ORs) and 95% confidence intervals (95% CIs) were calculated from a mixed
      effects logistic regression model. In total, 1596 patients with tunneled
      hemodialysis catheter-related bacteremia were divided into groups on the basis of
      treatment with systemic antibiotics (n=697), antibiotic lock solution (n=546), or
      guidewire exchange (n=353). Antibiotic lock solution and guidewire exchange had
      similar cure proportions that were superior to systemic antibiotics alone (OR,
      2.08; 95% CI, 1.25 to 3.45; P<0.01 for antibiotic lock solution; OR, 2.88; 95%
      CI, 1.82 to 4.55; P<0.001 for guidewire exchange versus systemic antibiotics).
      Cure proportions were highest for coagulase-negative staphylococci followed by
      gram-negative rods and Staphylococcus aureus. Among S. aureus infections,
      guidewire exchange led to a higher cure proportion than systemic antibiotics or
      antibiotic lock solution (OR, 3.33; 95% CI, 1.17 to 9.46; P=0.02; OR, 4.72; 95%
      CI, 1.79 to 12.46; P=0.002, respectively). Thus, results of this study suggest
      that tunneled hemodialysis catheter-related bacteremia should be treated with
      either guidewire exchange or antibiotic lock solution. Future studies should
      address prospectively whether one strategy is better than the other overall and
      for specific pathogens.

PMID- 24854264
TI  - Dynamic O-linked N-acetylglucosamine modification of proteins affects stress
      responses and survival of mesothelial cells exposed to peritoneal dialysis
      fluids.
AB  - The ability of cells to respond and survive stressful conditions is determined,
      in part, by the attachment of O-linked N-acetylglucosamine (O-GlcNAc) to proteins
      (O-GlcNAcylation), a post-translational modification dependent on glucose and
      glutamine. This study investigates the role of dynamic O-GlcNAcylation of
      mesothelial cell proteins in cell survival during exposure to glucose-based
      peritoneal dialysis fluid (PDF). Immortalized human mesothelial cells and primary
      mesothelial cells, cultured from human omentum or clinical effluent of PD
      patients, were assessed for O-GlcNAcylation under normal conditions or after
      exposure to PDF. The dynamic status of O-GlcNAcylation and effects on cellular
      survival were investigated by chemical modulation with 6-diazo-5-oxo-L-norleucine
      (DON) to decrease or O-(2-acetamido-2-deoxy-D-glucopyranosylidene)amino N-phenyl
      carbamate (PUGNAc) to increase O-GlcNAc levels. Viability was decreased by
      reducing O-GlcNAc levels by DON, which also led to suppressed expression of the
      cytoprotective heat shock protein 72. In contrast, increasing O-GlcNAc levels by
      PUGNAc or alanyl-glutamine led to significantly improved cell survival paralleled
      by higher heat shock protein 72 levels during PDF treatment. Addition of alanyl
      glutamine increased O-GlcNAcylation and partly counteracted its inhibition by
      DON, also leading to improved cell survival. Immunofluorescent analysis of
      clinical samples showed that the O-GlcNAc signal primarily originates from
      mesothelial cells. In conclusion, this study identified O-GlcNAcylation in
      mesothelial cells as a potentially important molecular mechanism after exposure
      to PDF. Modulating O-GlcNAc levels by clinically feasible interventions might
      evolve as a novel therapeutic target for the preservation of peritoneal membrane
      integrity in PD.

PMID- 24854265
TI  - Improving mutation screening in familial hematuric nephropathies through next
      generation sequencing.
AB  - Alport syndrome is an inherited nephropathy associated with mutations in genes
      encoding type IV collagen chains present in the glomerular basement membrane.
      COL4A5 mutations are associated with the major X-linked form of the disease, and
      COL4A3 and COL4A4 mutations are associated with autosomal recessive and dominant
      forms (thought to be involved in 15% and 1%-5% of the families, respectively) and
      benign familial hematuria. Mutation screening of these three large genes is time
      consuming and expensive. Here, we carried out a combination of multiplex PCR,
      amplicon quantification, and next generation sequencing (NGS) analysis of three
      genes in 101 unrelated patients. We identified 88 mutations and 6 variations of
      unknown significance on 116 alleles in 83 patients. Two additional indel
      mutations were found only by secondary Sanger sequencing, but they were easily
      identified retrospectively with the web-based sequence visualization tool
      Integrative Genomics Viewer. Altogether, 75 mutations were novel. Sequencing the
      three genes simultaneously was particularly advantageous as the mode of
      inheritance could not be determined with certainty in many instances. The
      proportion of mutations in COL4A3 and COL4A4 was notably high, and the autosomal
      dominant forms of Alport syndrome appear more frequently than reported
      previously. Finally, this approach allowed the identification of large COL4A3 and
      COL4A4 rearrangements not described previously. We conclude that NGS is
      efficient, reduces screening time and cost, and facilitates the provision of
      appropriate genetic counseling in Alport syndrome.

PMID- 24854266
TI  - Lineage tracing reveals distinctive fates for mesothelial cells and
      submesothelial fibroblasts during peritoneal injury.
AB  - Fibrosis of the peritoneal cavity remains a serious, life-threatening problem in
      the treatment of kidney failure with peritoneal dialysis. The mechanism of
      fibrosis remains unclear partly because the fibrogenic cells have not been
      identified with certainty. Recent studies have proposed mesothelial cells to be
      an important source of myofibroblasts through the epithelial-mesenchymal
      transition; however, confirmatory studies in vivo are lacking. Here, we show by
      inducible genetic fate mapping that type I collagen-producing submesothelial
      fibroblasts are specific progenitors of alpha-smooth muscle actin-positive
      myofibroblasts that accumulate progressively in models of peritoneal fibrosis
      induced by sodium hypochlorite, hyperglycemic dialysis solutions, or TGF-beta1.
      Similar genetic mapping of Wilms' tumor-1-positive mesothelial cells indicated
      that peritoneal membrane disruption is repaired and replaced by surviving
      mesothelial cells in peritoneal injury, and not by submesothelial fibroblasts.
      Although primary cultures of mesothelial cells or submesothelial fibroblasts each
      expressed alpha-smooth muscle actin under the influence of TGF-beta1, only
      submesothelial fibroblasts expressed alpha-smooth muscle actin after induction of
      peritoneal fibrosis in mice. Furthermore, pharmacologic inhibition of the PDGF
      receptor, which is expressed by submesothelial fibroblasts but not mesothelial
      cells, attenuated the peritoneal fibrosis but not the remesothelialization
      induced by hypochlorite. Thus, our data identify distinctive fates for injured
      mesothelial cells and submesothelial fibroblasts during peritoneal injury and
      fibrosis.

PMID- 24854267
TI  - HDL in children with CKD promotes endothelial dysfunction and an abnormal
      vascular phenotype.
AB  - Endothelial dysfunction begins in early CKD and contributes to cardiovascular
      mortality. HDL is considered antiatherogenic, but may have adverse vascular
      effects in cardiovascular disease, diabetes, and inflammatory conditions. The
      effect of renal failure on HDL properties is unknown. We studied the endothelial
      effects of HDL isolated from 82 children with CKD stages 2-5 (HDL(CKD)), who were
      free of underlying inflammatory diseases, diabetes, or active infections.
      Compared with HDL from healthy children, HDL(CKD) strongly inhibited nitric oxide
      production, promoted superoxide production, and increased vascular cell adhesion
      molecule-1 expression in human aortic endothelial cells, and reduced cholesterol
      efflux from macrophages. The effects on endothelial cells correlated with CKD
      grade, with the most profound changes induced by HDL from patients on dialysis,
      and partial recovery observed with HDL isolated after kidney transplantation.
      Furthermore, the in vitro effects on endothelial cells associated with increased
      aortic pulse wave velocity, carotid intima-media thickness, and circulating
      markers of endothelial dysfunction in patients. Symmetric dimethylarginine levels
      were increased in serum and fractions of HDL from children with CKD. In a
      longitudinal follow-up of eight children undergoing kidney transplantation, HDL
      induced production of endothelial nitric oxide, superoxide, and vascular cell
      adhesion molecule-1 in vitro improved significantly at 3 months after
      transplantation, but did not reach normal levels. These results suggest that in
      children with CKD without concomitant disease affecting HDL function, HDL
      dysfunction begins in early CKD, progressing as renal function declines, and is
      partially reversed after kidney transplantation. 

PMID- 24854268
TI  - Survival and hospitalization for intensive home hemodialysis compared with kidney
      transplantation.
AB  - Canadian patients receiving intensive home hemodialysis (IHHD; >=16 hours per
      week) have survival comparable to that of deceased donor kidney transplant
      recipients in the United States, but a comparison with Canadian kidney transplant
      recipients has not been conducted. We conducted a retrospective cohort study of
      consecutive, adult IHHD patients and kidney transplant recipients between 2000
      and 2011 at a large Canadian tertiary care center. The primary outcome was time
      to-treatment failure or death for IHHD patients compared with expanded criteria,
      standard criteria, and living donor recipients, and secondary outcomes included
      hospitalization rate. Treatment failure was defined as a permanent switch to an
      alternative dialysis modality for IHHD patients, and graft failure for transplant
      recipients. The cohort comprised 173 IHHD patients and 202 expanded criteria, 642
      standard criteria, and 673 living donor recipients. There were 285 events in the
      primary analysis. Transplant recipients had a reduced risk of treatment
      failure/death compared with IHHD patients, with relative hazards of 0.45 (95%
      confidence interval [95% CI], 0.31 to 0.67) for living donor recipients, 0.39
      (95% CI, 0.26 to 0.59) for standard criteria donor recipients, and 0.42 (95% CI,
      0.26 to 0.67) for expanded criteria donor recipients. IHHD patients had a lower
      hospitalization rate in the first year of treatment compared with standard
      criteria donor recipients and in the first 3 months of treatment compared with
      living donor and expanded criteria donor recipients. In this cohort, kidney
      transplantation was associated with superior treatment and patient survival, but
      higher early rates of hospitalization, compared with IHHD. 

PMID- 24854269
TI  - Pathogenesis of arrhythmias in a model of CKD.
AB  - Patients with CKD have an increased risk of cardiovascular mortality from
      arrhythmias and sudden cardiac death. We used a rat model of CKD (Cy/+) to study
      potential mechanisms of increased ventricular arrhythmias. Rats with CKD showed
      normal ejection fraction but hypertrophic myocardium. Premature ventricular
      complexes occurred more frequently in CKD rats than normal rats (42% versus 11%,
      P=0.18). By optical mapping techniques, action potential duration (APD) at 80% of
      repolarization was longer in CKD rats (78+/-4ms) than normal rats (63+/-3 ms,
      P<0.05) at a 200-ms pacing cycle length. Calcium transient (CaT) duration was
      comparable. Pacing cycle length thresholds to induce CaT alternans or APD
      alternans were longer in CKD rats than normal rats (100+/-7 versus 80+/-3 ms and
      93+/-6 versus 76+/-4 ms for CaT and APD alternans, respectively, P<0.05),
      suggesting increased vulnerability to ventricular arrhythmia. Ventricular
      fibrillation was induced in 9 of 12 CKD rats and 2 of 9 normal rats (P<0.05);
      early afterdepolarization occurred in two CKD rats but not normal rats. The mRNA
      levels of TGF-beta, microRNA-21, and sodium calcium-exchanger type 1 were
      upregulated, whereas the levels of microRNA-29, L-type calcium channel,
      sarco/endoplasmic reticulum calcium-ATPase type 2a, Kv1.4, and Kv4.3 were
      downregulated in CKD rats. Cardiac fibrosis was mild and not different between
      groups. We conclude that cardiac ion channel and calcium handling are abnormal in
      CKD rats, leading to increased vulnerability to early afterdepolarization,
      triggered activity, and ventricular arrhythmias.

PMID- 24854270
TI  - Polycystic kidney disease and cancer after renal transplantation.
AB  - Autosomal dominant polycystic kidney disease (ADPKD), the most common form of
      polycystic kidney disease (PKD), is a disorder with characteristics of neoplasia.
      However, it is not known whether renal transplant recipients with PKD have an
      increased risk of cancer. Data from the Scientific Registry of Transplant
      Recipients, which contains information on all solid organ transplant recipients
      in the United States, were linked to 15 population-based cancer registries in the
      United States. For PKD recipients, we compared overall cancer risk with that in
      the general population. We also compared cancer incidence in PKD versus non-PKD
      renal transplant recipients using Poisson regression, and we determined incidence
      rate ratios (IRRs) adjusted for age, sex, race/ethnicity, dialysis duration, and
      time since transplantation. The study included 10,166 kidney recipients with PKD
      and 107,339 without PKD. Cancer incidence in PKD recipients was 1233.6 per
      100,000 person-years, 48% higher than expected in the general population
      (standardized incidence ratio, 1.48; 95% confidence interval [95% CI], 1.37 to
      1.60), whereas cancer incidence in non-PKD recipients was 1119.1 per 100,000
      person-years. The unadjusted incidence was higher in PKD than in non-PKD
      recipients (IRR, 1.10; 95% CI, 1.01 to 1.20). However, PKD recipients were older
      (median age at transplantation, 51 years versus 45 years for non-PKD recipients),
      and after multivariable adjustment, cancer incidence was lower in PKD recipients
      than in others (IRR, 0.84; 95% CI, 0.77 to 0.91). The reason for the lower cancer
      risk in PKD recipients is not known but may relate to biologic characteristics of
      ADPKD or to cancer risk behaviors associated with ADPKD. 

PMID- 24854271
TI  - The kidney is the principal organ mediating klotho effects.
AB  - Klotho was discovered as an antiaging gene, and alpha-Klotho (Klotho) is
      expressed in multiple tissues with a broad set of biologic functions. Membrane
      bound Klotho binds fibroblast growth factor 23 (FGF23), but a soluble form of
      Klotho is also produced by alternative splicing or cleavage of the extracellular
      domain of the membrane-bound protein. The relative organ-specific contributions
      to the levels and effects of circulating Klotho remain unknown. We explored these
      issues by generating a novel mouse strain with Klotho deleted throughout the
      nephron (Six2-KL(-/-)). Klotho shedding from Six2-KL(-/-) kidney explants was
      undetectable and the serum Klotho level was reduced by approximately 80% in Six2
      KL(-/-) mice compared with wild-type littermates. Six2-KL(-/-) mice exhibited
      severe growth retardation, kyphosis, and premature death, closely resembling the
      phenotype of systemic Klotho knockout mice. Notable biochemical changes included
      hyperphosphatemia, hypercalcemia, hyperaldosteronism, and elevated levels of 1,25
      dihydroxyvitamin D and Fgf23, consistent with disrupted renal Fgf23 signaling.
      Kidney histology demonstrated interstitial fibrosis and nephrocalcinosis in
      addition to absent dimorphic tubules. A direct comparative analysis between Six2
      KL(-/-) and systemic Klotho knockout mice supports extensive, yet
      indistinguishable, extrarenal organ manifestations. Thus, our data reveal the
      kidney as the principal contributor of circulating Klotho and Klotho-induced
      antiaging traits. 

PMID- 24854272
TI  - Renal phosphate wasting in the absence of adenylyl cyclase 6.
AB  - Parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF-23) enhance
      phosphate excretion by the proximal tubule of the kidney by retrieval of the
      sodium-dependent phosphate transporters (Npt2a and Npt2c) from the apical plasma
      membrane. PTH activates adenylyl cyclase (AC) through PTH 1 receptors and
      stimulates the cAMP/PKA signaling pathway. However, the precise role and
      isoform(s) of AC in phosphate homeostasis are not known. We report here that mice
      lacking AC6 (AC6(-/-)) have increased plasma PTH and FGF-23 levels compared with
      wild-type (WT) mice but comparable plasma phosphate concentrations. Acute
      activation of the calcium-sensing receptor or feeding a zero phosphate diet
      almost completely suppressed plasma PTH levels in both AC6(-/-) and WT mice,
      indicating a secondary cause for hyperparathyroidism. Pharmacologic blockade of
      FGF receptors resulted in a comparable increase in plasma phosphate between
      genotypes, whereas urinary phosphate remained significantly higher in AC6(-/-)
      mice. Compared with WT mice, AC6(-/-) mice had reduced renal Npt2a and Npt2c
      protein abundance, with approximately 80% of Npt2a residing in lysosomes. WT mice
      responded to exogenous PTH with redistribution of Npt2a from proximal tubule
      microvilli to intracellular compartments and lysosomes alongside a PTH-induced
      dose-response relationship for fractional phosphate excretion and urinary cAMP
      excretion. These responses were absent in AC6(-/-) mice. In conclusion, AC6 in
      the proximal tubule modulates cAMP formation, Npt2a trafficking, and urinary
      phosphate excretion, which are highlighted by renal phosphate wasting in AC6(-/-)
      mice.

PMID- 24854273
TI  - The human response to acute enteral and parenteral phosphate loads.
AB  - The human response to acute phosphate (PO4) loading is poorly characterized, and
      it is unknown whether an intestinal phosphate sensor mechanism exists. Here, we
      characterized the human mineral and endocrine response to parenteral and duodenal
      acute phosphate loads. Healthy human participants underwent 36 hours of
      intravenous (IV; 1.15 [low dose] and 2.30 [high dose] mmol of PO4/kg per 24
      hours) or duodenal (1.53 mmol of PO4/kg per 24 hours) neutral sodium PO4 loading.
      Control experiments used equimolar NaCl loads. Maximum PO4 urinary excretory
      responses occurred between 12 and 24 hours and were similar for low-dose IV and
      duodenal infusion. Hyperphosphatemic responses were also temporally and
      quantitatively similar for low-dose IV and duodenal PO4 infusion. Fractional
      renal PO4 clearance increased approximately 6-fold (high-dose IV group) and 4
      fold (low-dose IV and duodenal groups), and significant reductions in plasma PO4
      concentrations relative to peak values occurred by 36 hours, despite persistent
      PO4 loading. After cessation of loading, frank hypophosphatemia occurred. The
      earliest phosphaturic response occurred after plasma PO4 and parathyroid hormone
      concentrations increased. Plasma fibroblast growth factor-23 concentration
      increased after the onset of phosphaturia, followed by a decrease in plasma
      1,25(OH)2D levels; alpha-Klotho levels did not change. Contrary to results in
      rodents, we found no evidence for intestinal-specific phosphaturic control
      mechanisms in humans. Complete urinary phosphate recovery in the IV loading
      groups provides evidence against any important extrarenal response to acute PO4
      loads.

PMID- 24854274
TI  - Lmx1b and FoxC combinatorially regulate podocin expression in podocytes.
AB  - Podocin is a key protein of the kidney podocyte slit diaphragm protein complex,
      an important part of the glomerular filtration barrier. Mutations in the human
      podocin gene NPHS2 cause familial or sporadic forms of renal disease owing to the
      disruption of filtration barrier integrity. The exclusive expression of NPHS2 in
      podocytes reflects its unique function and raises interesting questions about its
      transcriptional regulation. Here, we further define a 2.5-kb zebrafish nphs2
      promoter fragment previously described and identify a 49-bp podocyte-specific
      transcriptional enhancer using Tol2-mediated G0 transgenesis in zebrafish. Within
      this enhancer, we identified a cis-acting element composed of two adjacent DNA
      binding sites (FLAT-E and forkhead) bound by transcription factors Lmx1b and
      FoxC. In zebrafish, double knockdown of Lmx1b and FoxC orthologs using morpholino
      doses that caused no or minimal phenotypic changes upon individual knockdown
      completely disrupted podocyte development in 40% of injected embryos. Co
      overexpression of the two genes potently induced endogenous nphs2 expression in
      zebrafish podocytes. We found that the NPHS2 promoter also contains a cis-acting
      Lmx1b-FoxC motif that binds LMX1B and FoxC2. Furthermore, a genome-wide search
      identified several genes that carry the Lmx1b-FoxC motif in their promoter
      regions. Among these candidates, motif-driven podocyte enhancer activity of CCNC
      and MEIS2 was functionally analyzed in vivo. Our results show that podocyte
      expression of some genes is combinatorially regulated by two transcription
      factors interacting synergistically with a common enhancer. This finding provides
      insights into transcriptional mechanisms required for normal and pathologic
      podocyte functions.

PMID- 24854275
TI  - MicroRNA-24 antagonism prevents renal ischemia reperfusion injury.
AB  - Ischemia-reperfusion (I/R) injury of the kidney is a major cause of AKI.
      MicroRNAs (miRs) are powerful regulators of various diseases. We investigated the
      role of apoptosis-associated miR-24 in renal I/R injury. miR-24 was upregulated
      in the kidney after I/R injury of mice and in patients after kidney
      transplantation. Cell-sorting experiments revealed a specific miR-24 enrichment
      in renal endothelial and tubular epithelial cells after I/R induction. In vitro,
      anoxia/hypoxia induced an enrichment of miR-24 in endothelial and tubular
      epithelial cells. Transient overexpression of miR-24 alone induced apoptosis and
      altered functional parameters in these cells, whereas silencing of miR-24
      ameliorated apoptotic responses and rescued functional parameters in hypoxic
      conditions. miR-24 effects were mediated through regulation of H2A histone
      family, member X, and heme oxygenase 1, which were experimentally validated as
      direct miR-24 targets through luciferase reporter assays. In vitro, adenoviral
      overexpression of miR-24 targets lacking miR-24 binding sites along with miR-24
      precursors rescued various functional parameters in endothelial and tubular
      epithelial cells. In vivo, silencing of miR-24 in mice before I/R injury resulted
      in a significant improvement in survival and kidney function, a reduction of
      apoptosis, improved histologic tubular epithelial injury, and less infiltration
      of inflammatory cells. miR-24 also regulated heme oxygenase 1 and H2A histone
      family, member X, in vivo. Overall, these results indicate miR-24 promotes renal
      ischemic injury by stimulating apoptosis in endothelial and tubular epithelial
      cell. Therefore, miR-24 inhibition may be a promising future therapeutic option
      in the treatment of patients with ischemic AKI.

PMID- 24854276
TI  - Apolipoprotein B attenuates albuminuria-associated cardiovascular disease in
      prevention of renal and vascular endstage disease (PREVEND) participants.
AB  - Whether urinary albumin excretion relates to higher levels of atherogenic
      apolipoprotein B fractions in the nondiabetic population is uncertain. Such a
      relationship could explain, in part, the association of elevated urinary albumin
      excretion with cardiovascular disease risk. We assessed the relationship of
      urinary albumin excretion with apolipoprotein B fractions and determined whether
      the association of elevated urinary albumin excretion with incident
      cardiovascular events is modified by high apolipoprotein B fraction levels. We
      performed a prospective study on 8286 nondiabetic participants (580 participants
      with cardiovascular disease; 4.9 years median follow-up time) with fasting
      lipids, apolipoprotein B, and urinary albumin excretion determined at baseline.
      With adjustment for sex and age, micro- and macroalbuminuria were associated with
      increased apolipoprotein B fractions (non-HDL cholesterol, LDL cholesterol,
      triglycerides, and apolipoprotein B). All four apolipoprotein B fractions
      modified associations of urinary albumin excretion with incident cardiovascular
      disease (hazard ratios for interaction terms ranged from 0.89 to 0.94 with 95%
      confidence intervals ranging from 0.84 to 0.99 and P values ranging from 0.001 to
      0.02 by Cox proportional hazards modeling). These interactions remained present
      after additional adjustment for conventional risk factors, eGFR, cardiovascular
      history, and lipid-lowering and antihypertensive drug treatments. Such
      modification was also observed when urinary albumin excretion was stratified into
      normo-, micro-, and macroalbuminuria. We conclude that there is an association
      between elevated urinary albumin excretion and apolipoprotein B fraction levels
      and a negative interaction between these variables in their associations with
      incident cardiovascular events. Elevated urinary albumin excretion may share
      common causal pathways with high apolipoprotein B fractions in the pathogenesis
      of cardiovascular disease.

PMID- 24854277
TI  - Targeted deletion of p53 in the proximal tubule prevents ischemic renal injury.
AB  - The contribution of p53 to kidney dysfunction, inflammation, and tubular cell
      death, hallmark features of ischemic renal injury (IRI), remains undefined. Here,
      we studied the role of proximal tubule cell (PTC)-specific p53 activation on the
      short- and long-term consequences of renal ischemia/reperfusion injury in mice.
      After IRI, mice with PTC-specific deletion of p53 (p53 knockout [KO]) had
      diminished whole-kidney expression levels of p53 and its target genes, improved
      renal function, which was shown by decreased plasma levels of creatinine and BUN,
      and attenuated renal histologic damage, oxidative stress, and infiltration of
      neutrophils and macrophages compared with wild-type mice. Notably, necrotic cell
      death was attenuated in p53 KO ischemic kidneys as well as oxidant-injured p53
      deficient primary PTCs and pifithrin-alpha-treated PTC lines. Reduced oxidative
      stress and diminished expression of PARP1 and Bax in p53 KO ischemic kidneys may
      account for the decreased necrosis. Apoptosis and expression of proapoptotic p53
      targets, including Bid and Siva, were also significantly reduced, and cell cycle
      arrest at the G2/M phase was attenuated in p53 KO ischemic kidneys. Furthermore,
      IRI-induced activation of TGF-beta and the long-term development of inflammation
      and interstitial fibrosis were significantly reduced in p53 KO mice. In
      conclusion, specific deletion of p53 in the PTC protects kidneys from functional
      and histologic deterioration after IRI by decreasing necrosis, apoptosis, and
      inflammation and modulates the long-term sequelae of IRI by preventing
      interstitial fibrogenesis.

PMID- 24854280
TI  - Mind the gap.

PMID- 24854279
TI  - Autophagy regulates TGF-beta expression and suppresses kidney fibrosis induced by
      unilateral ureteral obstruction.
AB  - Autophagy is an evolutionarily conserved process that cells use to degrade and
      recycle cellular proteins and remove damaged organelles. During the past decade,
      there has been a growing interest in defining the basic cellular mechanism of
      autophagy and its roles in health and disease. However, the functional role of
      autophagy in kidney fibrosis remains poorly understood. Here, using GFP-LC3
      transgenic mice, we show that autophagy is induced in renal tubular epithelial
      cells (RTECs) of obstructed kidneys after unilateral ureteral obstruction (UUO).
      Deletion of LC3B (LC3(-/-) mice) resulted in increased collagen deposition and
      increased mature profibrotic factor TGF-beta levels in obstructed kidneys. Beclin
      1 heterozygous (beclin 1(+/-)) mice also displayed increased collagen deposition
      in the obstructed kidneys after UUO. We also show that TGF-beta1 induces
      autophagy in primary mouse RTECs and human renal proximal tubular epithelial (HK
      2) cells. LC3 deficiency resulted in increased levels of mature TGF-beta in
      primary RTECs. Under conditions of TGF-beta1 stimulation and autoinduction,
      inhibition of autolysosomal protein degradation by bafilomycin A1 increased
      mature TGF-beta protein levels without alterations in TGF-beta1 mRNA. These data
      suggest a novel intracellular mechanism by which mature TGF-beta1 protein levels
      may be regulated in RTECs through autophagic degradation, which suppresses kidney
      fibrosis induced by UUO. The dual functions of TGF-beta1, as an inducer of TGF
      beta1 autoinduction and an inducer of autophagy and TGF-beta degradation,
      underscore the multifunctionality of TGF-beta1.

PMID- 24854278
TI  - Aberrant glycosylation and localization of polycystin-1 cause polycystic kidney
      in an AQP11 knockout model.
AB  - We previously reported that disruption of the aquaporin-11 (AQP11) gene in mice
      resulted in cystogenesis in the kidney. In this study, we aimed to clarify the
      mechanism of cystogenesis in AQP11(-/-) mice. To enable the analyses of AQP11 at
      the protein level in vivo, AQP11 BAC transgenic mice (Tg(AQP11)) that express
      3*HA-tagged AQP11 protein were generated. This AQP11 localized to the endoplasmic
      reticulum (ER) of proximal tubule cells in Tg(AQP11) mice and rescued renal
      cystogenesis in AQP11(-/-) mice. Therefore, we hypothesized that the absence of
      AQP11 in the ER could result in impaired quality control and aberrant trafficking
      of polycystin-1 (PC-1) and polycystin-2 (PC-2). Compared with kidneys of wild
      type mice, AQP11(-/-) kidneys exhibited increased protein expression levels of PC
      1 and decreased protein expression levels of PC-2. Moreover, PC-1 isolated from
      AQP11(-/-) mice displayed an altered electrophoretic mobility caused by impaired
      N-glycosylation processing, and density gradient centrifugation of kidney
      homogenate and in vivo protein biotinylation revealed impaired membrane
      trafficking of PC-1 in these mice. Finally, we showed that the Pkd1(+/-)
      background increased the severity of cystogenesis in AQP11(-/-) mouse kidneys,
      indicating that PC-1 is involved in the mechanism of cystogenesis in AQP11(-/-)
      mice. Additionally, the primary cilia of proximal tubules were elongated in
      AQP11(-/-) mice. Taken together, these data show that impaired glycosylation
      processing and aberrant membrane trafficking of PC-1 in AQP11(-/-) mice could be
      a key mechanism of cystogenesis in AQP11(-/-) mice.

PMID- 24854281
TI  - In search of the fountain of youth.

PMID- 24854282
TI  - Nephrotic syndrome: components, connections, and angiopoietin-like 4-related
      therapeutics.
AB  - Nephrotic syndrome is recognized by the presence of proteinuria in excess of 3.5
      g/24 h along with hypoalbuminemia, edema, hyperlipidemia (hypertriglyceridemia
      and hypercholesterolemia), and lipiduria. Each component has been investigated
      individually over the past four decades with some success. Studies published
      recently have started unraveling the molecular basis of proteinuria and its
      relationship with other components. We now have improved understanding of the
      threshold for nephrotic-range proteinuria and the pathogenesis of
      hypertriglyceridemia. These studies reveal that modifying sialylation of the
      soluble glycoprotein angiopoietin-like 4 or changing key amino acids in its
      sequence can be used successfully to treat proteinuria. Treatment strategies on
      the basis of fundamental relationships among different components of nephrotic
      syndrome use naturally occurring pathways and have great potential for future
      development into clinically relevant therapeutic agents. 

PMID- 24854283
TI  - In vitro glucuronidation of five rhubarb anthraquinones by intestinal and liver
      microsomes from humans and rats.
AB  - Anthraquinones naturally distribute in many plants including rhubarb and have
      widespread applications throughout industry and medicine. Recent studies provided
      new insights in potential applications of these traditional laxative
      constituents. Glucuronidation was the main metabolic pathway of rhubarb
      anthraquinones in vivo. This study examined the activity and regioselectivity of
      glucuronidation of rhubarb anthraquinones (aloe-emodin, emodin, chrysophanol,
      physcion, rhein) in liver and intestinal microsomes from rats and humans, by
      comparing with the core structure danthron. All anthraquinones formed mono
      glucuronides and, except for rhein, the conjugation sites of the main metabolites
      were unambiguously identified. Two minor glucuronides of emodin were first
      reported together with the dominant emodin-3-O-beta-D-glucuronide. The
      substitution on the anthraquinone ring was crucial to the activity and
      regioselectivity of glucuronidation. In general, the activity was decreased
      greatly with a beta-COOH (rhein), while enhanced dramatically with a beta-OH
      (emodin). Glucuronidation showed an absolute preference towards beta-OH, followed
      by alpha-OH and beta-alcoholic OH. The glucuronidation activity and
      regioselectivity also varied slightly with organs and species. All glucuronides
      of aloe-emodin, emodin, chrysophanol and physcion were formed by multiple human
      UGT isoforms with 1A9 being the most prominent in most cases. The UGT2B subfamily
      (2B7 and 2B15) only showed high activity towards a beta-OH. In conclusion, the
      substitution at the anthraquinone ring was crucial to the rate and preference of
      glucuronidation. The high glucuronidation activity of UGT1A9 towards
      anthraquinones highlighted potential drug interactions.

PMID- 24854284
TI  - Design, synthesis and characterization of zinc-morin, a metal flavonol complex
      and evaluation of its antidiabetic potential in HFD-STZ induced type 2 diabetes
      in rats.
AB  - The present study deals with the synthesis, characterization of zinc-morin
      complex and evaluation of its antidiabetic efficacy in High Fat Diet (HFD)
      fedStreptozotocin (STZ) induced diabetic rats. Oral administration of zinc-morin
      complex to diabetic rats (5mg/kg body weight/day) for a period of 30 days
      resulted in the decreased levels of blood glucose and HbA1c. Oral administrations
      of the zinc-morin complex for 30 days significantly improved hyperglycemia,
      glucose intolerance, and insulin resistance. The elevated levels of lipid
      peroxides declined and the antioxidant competence was found to be improved in
      diabetic rats treated with the complex. The status of the lipid and lipoprotein
      profile in the serum was normalized upon treatment. Levels of TNFalpha decreased
      upon treatment with the complex. The altered levels of adipokines such as
      adiponectin and leptin were normalized upon treatment with the complex. In
      conclusion, the present study indicates that the zinc-morin complex possesses
      antidiabetic, antidyslipidemic and antioxidant potentials in HFD-fedSTZ induced
      diabetic rats.

PMID- 24854291
TI  - Outcomes after knee microfracture of chondral defects in alpine ski racers.
AB  - Articular cartilage defects of the knee have been shown to cause pain, swelling,
      decreased function, and suboptimal athletic performance. Treatment of elite-level
      athletes presenting with full-thickness chondral defects of the knee continues to
      be a challenge for orthopedic surgeons. The purpose of this study was to document
      outcomes in elite professional alpine ski racers after microfracture surgery.
      This study was approved by an institutional review board. All patients who
      competed in professional ski races recognized by International Ski Federation and
      had a full-thickness knee articular cartilage defect, treated with microfracture,
      by a single surgeon, were included in the study. All data were collected
      prospectively. At minimum 2 years following microfracture, all patients completed
      a questionnaire, including Lysholm score, Tegner activity scale, and patient
      satisfaction with outcome. Minimum 2-year follow-up was available for 18 of 20
      skiers (90%) at an average follow-up of 77 months (range, 24-255 months). Size of
      knee articular cartilage defect was larger in males (195 mm(2)) compared with
      females (155 mm(2)); however, this difference was not statistically significant
      (p > 0.05). Median postoperative Tegner activity scale was 10 (range, 4-10). Mean
      postoperative Lysholm score was 86 (range, 41-100). Median postoperative patient
      satisfaction score was 10 (range, 9-10). Out of the 20 skiers, 19 (95%) returned
      to competitive skiing. The age of the skier who did not return was 28 years. The
      average time from surgery to return to competition was 13.4 months (range, 0.5
      25.3 months). Average end-of-season overall World Cup ranking was calculated for
      the nine skiers before and after surgery. Of these nine skiers, six had an
      improved average overall World Cup ranking after microfracture. In this study,
      patient satisfaction with outcome and function were high following microfracture
      of full-thickness chondral lesions of the knee. Nearly all skiers returned to
      full competition. Microfracture is an acceptable treatment option for elite
      skiers who have full thickness articular cartilage lesions of the knee. 

PMID- 24854292
TI  - Surgical management of periprosthetic joint infection: one-stage exchange.
AB  - Although it does offer some advantages, the one-staged exchange in periprosthetic
      joint infection (PJI) remains rare in the orthopedic world. Besides the reduced
      number of surgical interventions for the patients, it is usually associated with
      a decreased in-hospital stay and quicker mobilization. Furthermore, it might be
      the more cost-effective approach and allows for a reduced duration of
      postoperative systemic antibiotics, usually less than 14 days. Technically, the
      presence of a positive culture by preoperative aspiration or biopsy and
      respective antibiogram is mandatory. A cemented implant fixation using specified
      topic antibiotics, based on the antibiogram, is treatment of choice for one
      staged procedures. The overall success is based on the well-defined and detailed
      intrahospital infrastructure, including a meticulous preoperative planning, joint
      aspiration regime, and aggressive intraoperative surgical approach. This article
      describes the one-staged exchange in infected PJI of the knee joint, which has
      been established 40 years ago in the HELIOS ENDO-Klinik Hamburg, Germany. 

PMID- 24854293
TI  - Effects of sonication and ultraviolet-C treatment as a hurdle concept on quality
      attributes of Chokanan mango (Mangifera indica L.) juice.
AB  - The growing demand for fresh-like food products has encouraged the development of
      hurdle technology of non-thermal processing. In this study, freshly squeezed
      Chokanan mango juice was treated by paired combinations of sonication (for 15 and
      30 min at 25 C, 40 kHz frequency) and UV-C treatment (for 15 and 30 min at 25 C).
      Selected physicochemical properties, antioxidant activities, microbial
      inactivation and other quality parameters of combined treated juice were compared
      to conventional thermal treatment (at 90 C for 60 s). After thermal and combined
      treatment, no significant changes occurred in physicochemical properties. A
      significant increase in extractability of carotenoids (15%), polyphenols (37%),
      flavonoids (35%) and enhancement in antioxidant capacity was observed after
      combined treatment. Thermal and combined treatment exhibited significant
      reduction in microbial load. Results obtained support the use of sonication and
      UV-C in a hurdle technology to improve the quality of Chokanan mango juice along
      with safety standards. 

PMID- 24854294
TI  - Effect of tiger nut-derived products in gluten-free batter and bread.
AB  - Tiger nut is a tuber used to produce tiger nut milk that yields a high quantity
      of solid waste, which can be dried and used as fiber source. The objective of
      this paper was to evaluate the quality of gluten-free bread formulated with
      different tiger nut-derived products in order to substitute soya flour (which is
      an allergen ingredient) and, at the same time, increase the use of tiger nut
      derived products. Four gluten-free formulations based on corn starch and
      containing tiger nut milk, tiger nut milk by-product, tiger nut flour, or soya
      flour (as reference formulation) were studied. Tiger nut milk increased G' of
      gluten-free batter and rendered breads with the softest crumb (502.46 g +/-
      102.05), the highest loaf-specific volume (3.35 cm(3)/g +/- 0.25), and it was
      mostly preferred by consumers (61.02%). Breads elaborated with tiger nut flour
      had similar characteristics than soya flour breads (except in color and crumb
      structure). The addition of tiger nut milk by-product resulted in a hard (1047.64
      g +/- 145.74) and dark (L(*)  = 70.02 +/- 3.38) crumb bread, which was the least
      preferred by consumers. Results showed that tiger nut is a promising ingredient
      to formulate gluten-free baked products. 

PMID- 24854295
TI  - Identification of epicatechin as one of the key bioactive constituents of
      polyphenol-enriched extracts that demonstrate an anti-allergic effect in a murine
      model of food allergy.
AB  - Polyphenols are naturally derived bioactive compounds with numerous reported
      health benefits. We have previously reported on the beneficial effect of a
      polyphenol-enriched apple extract in a murine model of food allergy. The
      objectives of the present study were to elucidate the class of bioactive
      polyphenols that exhibit a beneficial anti-allergic effect and to assess whether
      the protective effect matches the in vivo bioavailable metabolite concentrations.
      Female BALB/c mice were sensitised to ovalbumin (OVA) following the protocol of a
      well-established murine model of food allergy. They were fed diets containing
      polyphenol-enriched extracts or purified epicatechin for 8 d after the last
      sensitisation. The sensitised mice were orally challenged with OVA after the
      intervention. The allergy symptoms, in addition to allergen-specific serum Ig
      concentrations and gene expression profiles in the intestine, of the control and
      treated mice were compared. Plasma samples were collected to compare the
      concentrations of bioavailable epicatechin metabolites in the treatment groups.
      Polyphenol-enriched fruit extracts containing epicatechin exhibited a significant
      anti-allergic effect in vivo. This effect was unambiguously attributed to
      epicatechin, as oral administration of this purified polyphenol to sensitised
      mice by inclusion in their diet modulated allergy symptoms in a dose-dependent
      manner. Immune parameters were also affected by the administration of
      epicatechin. Bioavailability measurements in plasma indicated that the
      attenuation of allergy symptoms could be due to the higher concentrations of
      bioavailable epicatechin metabolites. In conclusion, epicatechin is a key
      bioactive polyphenol that has the ability to modulate allergy outcomes in
      sensitised mice.

PMID- 24854296
TI  - Novel, selective vitamin D analog suppresses parathyroid hormone in uremic
      animals and postmenopausal women.
AB  - BACKGROUND: The use of 1alpha-hydroxylated vitamin D therapy to control secondary
      hyperparathyroidism in renal failure patients has been a success story,
      culminating with the demonstration of increased life expectancy in patients
      treated with these compounds. However, hypercalcemic episodes have been a
      recurrent problem with these therapies and have resulted in the added use of
      calcium mimetics. Clearly there is good reason to search for improved vitamin D
      therapy. In our inventory of vitamin D compounds, 2-methylene-19-nor-(20S)
      1alpha,25-dihydroxyvitamin D3 (2MD) surfaced as a potential candidate. This was
      based on its preferential localization in the parathyroid gland and a clear
      suppression of serum parathyroid hormone (PTH) levels without a change in serum
      calcium in a clinical trial in postmenopausal women. METHODS: 2MD has now been
      tested in the rat 5/6-nephrectomy model of renal failure, and in postmenopausal
      women to determine if it can suppress serum PTH at doses that do not elevate
      serum calcium and serum phosphorus concentrations. RESULTS: Daily oral treatment
      of uremic rats on 2.5 ng/bw/day of 2MD dramatically suppressed PTH without a
      change in serum calcium or serum phosphorus. Further, PTH was suppressed in
      postmenopausal women after only 3 daily oral doses of 2MD that continued for 4
      weeks with no change in serum calcium or serum phosphorus. CONCLUSION: These
      results coupled with a pharmacokinetic half-life of ~24 h suggest that 2MD given
      either daily or at the time of dialysis may be a superior therapy for secondary
      hyperparathyroidism in chronic renal failure patients.

PMID- 24854297
TI  - Hospital-acquired pressure ulcers and risk of hospital mortality in intensive
      care patients on mechanical ventilation.
AB  - RATIONALE, AIMS AND OBJECTIVES: Pressure ulcers (PUs) are a common and serious
      complication in critically ill patients. The aim of this study was to evaluate
      the relationship between the development of a PU and hospital mortality in
      patients requiring mechanical ventilation (MV) in an intensive care unit (ICU).
      METHODS: A prospective cohort study was performed over two years in patients
      requiring MV for >= 24 hours in a medical-surgical ICU. Primary outcome measure
      was hospital mortality and main independent variable was the development of a PU
      grade >= II. Hazard ratios (HRs) were calculated using a Cox model with time
      dependent covariates. RESULTS: Out of 563 patients in the study, 110 (19.5%)
      developed a PU. Overall hospital mortality was 48.7%. In the adjusted
      multivariate model, PU onset was a significant independent predictor of mortality
      (adjusted HR, 1.28; 95% confidence interval, 1.003-1.65; P = 0.047). The model
      also included the Acute Physiology and Chronic Health Evaluation II score, total
      Sequential Organ Failure Assessment on day 3, hepatic cirrhosis and medical
      admission. CONCLUSION: Within the limitations of a single-centre approach, PU
      development appears to be associated with an increase in mortality among patients
      requiring MV for 24 hours or longer.

PMID- 24854298
TI  - Pressure, perfusion, and compartments: challenges for the acute care surgeon.

PMID- 24854299
TI  - Delayed hemorrhagic complications in the nonoperative management of blunt splenic
      trauma: early screening leads to a decrease in failure rate.
AB  - BACKGROUND: Delayed splenic rupture is the Achilles' heel of nonoperative
      management (NOM) for blunt splenic injury (BSI). Early computed tomographic (CT)
      scanning for features suggesting high risk of nonoperative failure, splenic
      pseudoaneurysms (SPAs), and arterial extravasation (AE), in concert with the
      appropriate use of splenic arterial embolization (SAE) is a viable method to
      reduce rates of failure of NOM. We report our 12-ear experience with a protocol
      for mandatory repeat CT evaluation at 48 hours and selective SAE. METHODS: A
      retrospective cohort analysis was performed on all consecutive adult trauma
      patients with BSI between 1995 and 2012. We evaluated an early/control (1995
      1999) and a present/intervention (2000-2012) cohort in which SAE became available
      and 48-hour CT scans were implemented. RESULTS: The study included 773 patients
      (157 early vs. 616 present) with BSI. The proportion of patients managed
      nonoperatively (53% vs. 77%, p < 0.01) and overall splenic salvage rate (46% vs.
      77%, p < 0.01) were improved in the present cohort. Among patients selected for
      NOM, there was a significant improvement in the failure rate of NOM (12% vs.
      0.6%, p < 0.01) as well as in the length of hospital stay (8 days vs. 6 days, p <
      0.01). Delayed development of SPA and/or AE was detected in 6% of BSI in the
      present cohort and was distributed among all grades of injury. CONCLUSION: The
      delayed development of SPA and AE is not an entirely rare event following BSI.
      Reevaluation with CT at 48 hours following admission and the use of SAE
      significantly decrease the failure rate of NOM. LEVEL OF EVIDENCE: Therapeutic
      study, level III.

PMID- 24854301
TI  - The role of endoscopic retrograde pancreatography in pancreatic trauma: a
      critical appraisal of 48 patients treated at a tertiary institution.
AB  - BACKGROUND: Endoscopic retrograde pancreatography (ERP) is useful in the
      diagnosis and treatment of selected patients with pancreatic trauma. We analyzed
      the role of ERP in treating persistent complications of pancreatic injuries at a
      tertiary institution. METHODS: Patients with pancreatic trauma who underwent ERP
      were identified from a prospective database of 426 pancreatic injuries from
      January 1983 to January 2011. Patient demographics, mechanism of injury, time to
      presentation, method of diagnosis, associated injuries, clinical management,
      endoscopic interventions and their timing, surgical treatment, and patient
      outcomes were evaluated. RESULTS: Forty-eight patients underwent ERP after blunt
      (n = 26) or penetrating (n = 22) pancreatic injury. Median time from injury to
      ERP was 38 days (range, 2-365 days). Diagnostic ERP was successful in 47
      patients. In 11 patients, ERP demonstrated an intact main duct with minor
      peripheral injuries, and no further intervention was required. A pancreatic
      fistula was demonstrated in 24, a main pancreatic duct stricture in 12, and a
      pseudocyst in 10 patients. Fifteen patients had a pancreatic duct sphincterotomy,
      seven had a pancreatic stent inserted, and six had an endoscopic pseudocyst
      drainage. Ten patients ultimately required surgery, seven of whom had
      demonstrated a severe pancreatic duct stricture. Operations performed following
      ERP were distal pancreatectomy (n = 6), pancreaticojejunostomy (n = 3) and cyst
      jejunostomy (n = 1). CONCLUSION: ERP allowed one quarter of the patients to be
      treated conservatively. Half had a successful intervention by ERP. Success was
      most likely in those with fistulae and pseudocysts. Surgery was ultimately
      avoided in more than three quarters of the patients. LEVEL OF EVIDENCE:
      Therapeutic study, level V.

PMID- 24854300
TI  - Management and outcome of patients with blunt splenic injury and preexisting
      liver cirrhosis.
AB  - BACKGROUND: The response of liver cirrhosis (LC) patients to abdominal trauma,
      including blunt splenic injury (BSI) is unfavorable. To better understand the
      response to BSI in LC patients, the present study reviewed a much larger group of
      such patients, derived from the National Trauma Data Bank. METHODS: The National
      Trauma Data Bank was queried for 2002 to 2010, and all adult BSI patients without
      severe brain trauma were identified. LC and non-LC patients were compared using
      nonoperative management (NOM) failure and mortality as primary outcomes.
      Predictors of these outcomes in LC patients were identified. RESULTS: Of the
      77,753 identified BSI patients, 289 (0.37%) had LC. Overall, 90% of the patients
      underwent initial NOM (86% in LC and 90% in non-LC patients, p = 0.091) with a
      global 90% success rate. Compared with non-LC patients, LC patients had a lower
      NOM success rate (83% vs. 90%, p = 0.004) despite increased use of splenic artery
      angioembolization (13% vs. 8%, p = 0.001). LC patients also had more
      complications per patient, an increased hospital and intensive care unit lengths
      of stay, and a higher mortality (22% vs. 6%, p < 0.0001), which was independent
      of the treatment paradigm. In the LC group, mortality in those who underwent
      immediate surgery was 35% versus 46% in failed NOM (p = 0.418) and 14% (p =
      0.019) in successful NOM patients. LC patients who did not require surgery were
      more likely to survive than those who had surgery alone (adjusted odds ratio
      [AOR], 0.30). Preexisting coagulopathy (AOR, 3.28) and Grade 4 to 5 BSI (AOR,
      11.6) predicted NOM failure in LC patients, whereas male sex (AOR, 4.34),
      hypotension (AOR, 3.15), preexisting coagulopathy (AOR, 3.06), and Glasgow Coma
      Scale (GCS) score of less than 13 (AOR, 6.33) predicted mortality. CONCLUSION: LC
      patients have a higher rate of complications, mortality, and NOM failure compared
      with non-LC patients. Because LC patients with failed NOM have a mortality rate
      similar to those undergoing immediate surgery, judgment must be exerted in
      selecting initial management options. LEVEL OF EVIDENCE: Prognostic/epidemiologic
      study, level III.

PMID- 24854302
TI  - Trials of nonoperative management exceeding 3 days are associated with increased
      morbidity in patients undergoing surgery for uncomplicated adhesive small bowel
      obstruction.
AB  - BACKGROUND: Controversy exists over how long trials of nonoperative management
      should be pursued in patients with uncomplicated adhesive small bowel
      obstructions (ASBOs) before deciding to proceed with surgery. The purpose of this
      study was to determine the effect of incremental delays in surgery on the 30-day
      postoperative outcomes of patients undergoing surgery for uncomplicated ASBO.
      METHODS: American College of Surgeons National Surgical Quality Improvement
      Program 2005-2011 data were used to identify patients with uncomplicated ASBO in
      whom a trial of nonoperative management was attempted. Multivariate logistic or
      linear regression model was created to determine the independent association
      between the length of preoperative hospitalization and 30-day postoperative
      outcomes after adjustment for patient- and procedure-related factors. RESULTS: A
      total of 9,297 patients were included in the study. The 30-day postoperative
      mortality and overall morbidity rates of the entire cohort were 4.4% and 29.6%,
      respectively. The median postoperative length of hospitalization was 7 days
      (interquartile range, 5-11 days). After risk adjustment, there was no association
      between preoperative length of hospitalization and 30-day postoperative
      mortality. In contrast, increased 30-day overall morbidity was observed in
      patients who received their operation after a preoperative length of
      hospitalization of 3 days compared with earlier in their hospitalization.
      Furthermore, an increased postoperative length of hospitalization was found in
      patients who were operated on after a preoperative length of hospitalization of 4
      days. CONCLUSION: Trials of nonoperative management for uncomplicated ASBO
      exceeding 3 days are associated with increased morbidity and postoperative length
      of hospitalization. These trials should therefore generally not extend beyond
      this time point. LEVEL OF EVIDENCE: Therapeutic study, level IV.

PMID- 24854303
TI  - Do all trauma patients benefit from tranexamic acid?
AB  - BACKGROUND: This study tested the hypothesis that early routine use of tranexamic
      acid (TXA) reduces mortality in a subset of the most critically injured trauma
      intensive care unit patients. METHODS: Consecutive trauma patients (n = 1,217)
      who required emergency surgery (OR) and/or transfusions from August 2009 to
      January 2013 were reviewed. At surgeon discretion, TXA was administered at a
      median of 97 minutes (1-g bolus then 1-g over 8 hours) to 150 patients deemed
      high risk for hemorrhagic death. With the use of propensity scores based on age,
      sex, traumatic brain injury (TBI), mechanism of injury, systolic blood pressure,
      transfusion requirements, and Injury Severity Score (ISS), these patients were
      matched to 150 non-TXA patients. RESULTS: The study population was 43 years old,
      86% male, 54% penetrating mechanism of injury, 25% TBI, 28 ISS, with 22%
      mortality. OR was required in 78% at 86 minutes, transfusion was required in 97%
      at 36 minutes, and 75% received both. For TXA versus no TXA, more packed red
      blood cells and total fluid were required, and mortality was 27% versus 17% (all
      p < 0.05). The effects of TXA were similar in those with or without TBI, although
      ISS, fluid, and mortality were all higher in the TBI group. Mortality associated
      with TXA was influenced by the timing of administration (p < 0.05), but any
      benefit was eliminated in those who required more than 2,000-mL packed red blood
      cells, who presented with systolic blood pressure of less than 120 mm Hg or who
      required OR (all p < 0.05). CONCLUSION: For the highest injury acuity patients,
      TXA was associated with increased, rather than reduced, mortality, no matter what
      time it was administered. This lack of benefit can probably be attributed to the
      rapid availability of fluids and emergency OR at this trauma center. Prospective
      studies are needed to further identify conditions that may override the benefits
      from TXA. LEVEL OF EVIDENCE: Therapeutic study, level IV.

PMID- 24854304
TI  - Automated prediction of early blood transfusion and mortality in trauma patients.
AB  - BACKGROUND: Prediction of blood transfusion needs and mortality for trauma
      patients in near real time is an unrealized goal. We hypothesized that analysis
      of pulse oximeter signals could predict blood transfusion and mortality as
      accurately as conventional vital signs (VSs). METHODS: Continuous VS data were
      recorded for direct admission trauma patients with abnormal prehospital shock
      index (SI = heart rate [HR] / systolic blood pressure) greater than 0.62.
      Predictions of transfusion during the first 24 hours and in-hospital mortality
      using logistical regression models were compared with DeLong's method for areas
      under receiver operating characteristic curves (AUROCs) to determine the optimal
      combinations of prehospital SI and HR, continuous photoplethysmographic (PPG),
      oxygen saturation (SpO2), and HR-related features. RESULTS: We enrolled 556
      patients; 37 received blood within 24 hours; 7 received more than 4 U of red
      blood cells in less than 4 hours or "massive transfusion" (MT); and 9 died. The
      first 15 minutes of VS signals, including prehospital HR plus continuous PPG, and
      SpO2 HR signal analysis best predicted transfusion at 1 hour to 3 hours, MT, and
      mortality (AUROC, 0.83; p < 0.03) and no differently (p = 0.32) from a model
      including blood pressure. Predictions of transfusion based on the first 15
      minutes of data were no different using 30 minutes to 60 minutes of data
      collection. SI plus PPG and SpO2 signal analysis (AUROC, 0.82) predicted 1-hour
      to 3-hour transfusion, MT, and mortality no differently from pulse oximeter
      signals alone. CONCLUSION: Pulse oximeter features collected in the first 15
      minutes of our trauma patient resuscitation cohort, without user input, predicted
      early MT and mortality in the critical first hours of care better than the
      currently used VS such as combinations of HR and systolic blood pressure or
      prehospital SI alone. LEVEL OF EVIDENCE: Therapeutic/prognostic study, level II.

PMID- 24854305
TI  - Management of lower extremity vascular injuries in pediatric trauma patients: a
      single Level I trauma center experience.
AB  - BACKGROUND: Traumatic vascular injuries of the lower extremity in the pediatric
      population are rare but can result in significant morbidity. We aimed at
      describing our experience with such complex injuries, with associated patterns of
      injury, diagnostic and therapeutic challenges, and outcomes. METHODS: From
      January 2006 to December 2011, 2,844 pediatric trauma patients presented at the
      Ryder Trauma Center, an urban Level I trauma center in Miami, Florida. Among
      them, 18 patients (0.6%) were evaluated for lower extremity traumatic vascular
      injuries. Variables collected included age, sex, mechanism of injury, and
      clinical status at presentation. Surgical data included vessel injury, technical
      aspects of repair, associated complications, and outcomes. RESULTS: Mean (SD) age
      was +/- 14.7 (2.6) years (range, 6-17 years), with 17 males (94.4%). Of the 18
      traumatic pediatric patients, 32 vascular injuries were identified. All arterial
      injuries underwent definitive operative repair. Primary repair was performed in
      two patients (11.1%), six (33.3%) required saphenous vein interposition grafting
      as initial procedure, and eight (44.4%) underwent polytetrafluoroethylene
      grafting. Ligation was performed in major venous injuries and deep profunda
      branches. The overall survival in this series was 94.4%. CONCLUSION: Peripheral
      vascular injuries of the lower extremity in the pediatric population can result
      in acceptable outcomes if managed early and aggressively. Surgical principles of
      vascular surgery are similar to those applied to an adult. We recommend that
      these injuries should be managed in a tertiary specialized center with a
      multidisciplinary team of trauma surgeons, and pediatricians, which can
      potentially decrease morbidity and mortality. LEVEL OF EVIDENCE: Epidemiologic
      study, level III.

PMID- 24854306
TI  - Critical illness-related corticosteroid insufficiency after multiple traumas: a
      multicenter, prospective cohort study.
AB  - BACKGROUND: Given that the observed prevalence and time course of critical
      illness-related corticosteroid insufficiency (CIRCI) remain inconsistent in
      trauma patients, the present study was designed to investigate the prevalence,
      time course, and effect of CIRCI on the outcome of critically ill patients with
      multiple injuries. METHODS: In this multicenter, prospective cohort study,
      patients with multiple injuries in seven intensive care units in China were
      enrolled. Adrenocorticotropic hormone (ACTH) stimulation tests were performed by
      administering intravenously 250 MUg of synthetic ACTH on Days 1, 2, 3, 5, and 7
      after traumatic injury. CIRCI was defined as baseline cortisol level of less than
      10 MUg/dL or a Deltacortisol (difference baseline and highest cortisol level at
      30 or 60 minutes after ACTH stimulation) less than 9 MUg/dL. The incidence and
      time course of CIRCI and 28-day mortality were recorded. RESULTS: CIRCI occurred
      in 54.3% (38 of 70) of the patients with multiple injuries, including 10 patients
      with total cortisol level of less than 10 MUg/dL and 28 patients with
      Deltacortisol of less than 9 MUg/dL. Most (94.7%) diagnosis of CIRCI was made in
      the first 48 hours after traumatic injury. The CIRCI patients had significantly
      more severe illness on the day of admission. At each time point, the baseline
      cortisol level was comparable between the CIRCI and non-CIRCI patients, while
      Deltacortisol in the CIRCI group was significantly lower compared with the non
      CIRCI group. The CIRCI patients with a Deltacortisol of less than 9 MUg/dL had a
      significantly higher 28-day mortality (39.3%) compared with those with a baseline
      cortisol level of less than 10 MUg/dL (10.0%) and non-CIRCI patients (6.3%). Only
      Deltacortisol of less than 9 MUg/dL but not baseline cortisol level of less than
      10 MUg/dL seemed to be an independent risk factor for death (odds ratio, 1.19; p
      = 0.023). CONCLUSION: CIRCI is common in critically ill trauma population and
      usually occurs in the early stages. Only the results of the ACTH stimulation test
      but not baseline cortisol level was associated with poor prognosis. LEVEL OF
      EVIDENCE: Prognostic study, level II.

PMID- 24854307
TI  - Recurrent kidney injury in critically ill surgical patients is common and
      associated with worse outcomes.
AB  - Supplemental digital content is available in the text. BACKGROUND: Acute kidney
      injury (AKI) is common in critically ill surgery patients. Patients who recover
      are at risk for recurrence, but recurrent kidney injury (RKI) is not well
      studied. METHODS: This was a retrospective 12-month cohort study of adults
      consecutively admitted to a noncardiac, non-trauma surgical intensive care unit.
      Patients were identified from a prospective critical care database, and kidney
      injury events were diagnosed and graded by RIFLE criteria. Patients who recovered
      from AKI were analyzed, and the primary end point was RKI (defined as kidney
      injury occurring after recovery from an index AKI event). Outcomes were inpatient
      and 1-year mortality, inpatient lengths of stay, and discharge creatinine.
      RESULTS: Of 624 patients, 296 (47%) had AKI and 216 (73%) recovered. Of these, 68
      (31%) developed RKI. AKI in progress on hospital admission was associated with
      recurrence, but otherwise RKI and non-RKI patients had similar demographics,
      comorbidities, and inpatient clinical factors. Recurrence was associated with
      significantly higher inpatient and 12-month mortality, greater resource use, and
      worse discharge renal function. CONCLUSION: RKI is common among critically ill
      surgical patients who recover from an index episode. Recurrence is a clinically
      significant event and is associated with worse renal and patient outcomes. Future
      studies should further define this process. LEVEL OF EVIDENCE: Prognostic and
      epidemiologic study, level III.

PMID- 24854308
TI  - Resuscitation with amiodarone increases survival after hemorrhage and ventricular
      fibrillation in pigs.
AB  - Supplemental digital content is available in the text. BACKGROUND: The aim of
      this experimental study was to compare survival and hemodynamic effects of a low
      dose amiodarone and vasopressin compared with vasopressin in hypovolemic cardiac
      arrest model in piglets. METHODS: Eighteen anesthetized male piglets (with a
      weight of 25.3 [1.8] kg) were bled approximately 30% of the total blood volume
      via the femoral artery to a mean arterial blood pressure of 35 mm Hg in a 15
      minute period. Afterward, the piglets were subjected to 4 minutes of untreated
      ventricular fibrillation followed by 11 minutes of open-chest cardiopulmonary
      resuscitation. At 5 minutes, circulatory arrest amiodarone 1 mg/kg was
      intravenously administered in the amiodarone group (n = 9), while the control
      group received the same amount of saline (n = 9). At the same time, all piglets
      received vasopressin 0.4 U/kg intravenously administered and hypertonic
      hyperoncotic solution 3-mL/kg infusion for 20 minutes. Internal defibrillation
      was attempted from 7 minutes of cardiac arrest to achieve restoration of
      spontaneous circulation. The experiment was terminated 3 hours after
      resuscitation. RESULTS: Three-hour survival was greater in the amiodarone group
      (p = 0.02). After the successful resuscitation, the amiodarone group piglets had
      significantly lower heart rate as well as greater systolic, diastolic, and mean
      arterial pressure. Troponin I plasma concentrations were lower and urine output
      was greater in the amiodarone group. CONCLUSION: Combined resuscitation with
      amiodarone and vasopressin after hemorrhagic circulatory arrest resulted in
      greater 3-hour survival, better preserved hemodynamic parameters, and smaller
      myocardial injury compared with resuscitation with vasopressin only.

PMID- 24854309
TI  - Efficacy of 17alpha-ethynylestradiol-3-sulfate for severe hemorrhage in minipigs
      in the absence of fluid resuscitation.
AB  - BACKGROUND: Of the potentially survivable US battlefield deaths from 2001 to
      2011, 80% to 91% were caused by severe hemorrhage. We subjected minipigs to acute
      severe blood loss, administered a single dose of 17alpha-ethynylestradiol-3
      sulfate (EE-3-SO4) without resuscitative fluids, and determined survival as well
      as cardiovascular, biochemical, and physiologic response parameters. METHODS:
      Following controlled removal of 60% circulating blood volume over 1 hour,
      minipigs received EE-3-SO4 at 0, 1, 3, or 5-mg/mL saline per kilogram of body
      weight in Experiment 1 (n = 25) and 0-, 0.1-, 0.3-, or 1-mg/mL saline per
      kilogram in Experiment 2 (n = 23). Survival times and response parameters were
      recorded for the next 6 hours. RESULTS: Median survival times of the minipigs
      receiving 1 mg/kg (257 minutes and 360 minutes) were 1.8 times and 5 times those
      of the control group (140 minutes and 65 minutes) in Experiments 1 and 2,
      respectively. For both experiments combined, the log-rank p value was 0.0002, and
      the number of animals alive at 6 hours was 6 (50%) of 12 in the 1-mg/kg groups
      versus 0 (0%) of 12 in the control groups. Early increases in glucose, lactate,
      potassium, and phosphate as well as decreases in bicarbonate and mean arterial
      pressure correlated with shorter survival times. CONCLUSION: Administration of a
      single dose of 1-mg/kg EE-3-SO4 in 1-mL/kg of saline following severe hemorrhage
      increased survival in 60% acutely bled minipigs by 3.5-fold. Slightly elevated
      blood pressure values, more physiologic values of oxidative phosphorylation
      parameters, and lower elevations of possible tissue necrosis parameters
      correlated with longer survival time. These results support the further product
      development of EE-3-SO4 for the indication of severe hemorrhage when standard
      resuscitative fluids are not available.

PMID- 24854310
TI  - Improvement of ventilation-induced lung injury in a rodent model by inhibition of
      inhibitory kappaB kinase.
AB  - BACKGROUND: Inhibition of nuclear factor kappaB (NF-kappaB) activation is a well
      know strategy to ameliorate ventilation-induced lung injury (VILI). Inhibitory
      kappaB kinase (IKK) plays a key role in the regulation of NF-kappaB activation.
      In this study, we determined whether inhibition of IKK by an IKK inhibitor exerts
      lung protection in a rat model of VILI. METHODS: Anesthetized and mechanically
      ventilated Sprague-Dawley rats were randomly assigned to a standard (tidal
      volume, 8 mL/kg) or high-tidal volume (tidal volume, 25 mL/kg) ventilation group.
      An IKK inhibitor (IKK 16) or vehicle was administrated 1 hour before the
      induction of VILI. All groups were ventilated and observed for 5 hours. RESULTS:
      High-pressure ventilation caused activation of NF-kappaB, increased pulmonary
      inflammatory mediator levels, lung edema, and impairment of gas exchange. The IKK
      inhibitor treatment significantly reduced these changes and increased interleukin
      10 levels, heme oxygenase 1 activity, protein kinase B (Akt) phosphorylation
      levels, and nuclear amounts of nuclear factor E2-related factor 2 protein.
      CONCLUSION: IKK may be a therapeutic target for VILI. An IKK inhibitor, IKK 16,
      can dampen VILI in rats. The beneficial effect of the IKK 16 may be mediated
      through the inhibition of NF-kappaB pathway and up-regulation of nuclear factor
      E2-related factor 2-regulated heme oxygenase 1 through the activation of the
      phosphatidylinositol 3 kinase/Akt.

PMID- 24854311
TI  - Induced hypothermia reduces the hepatic inflammatory response in a swine multiple
      trauma model.
AB  - BACKGROUND: Mild therapeutic hypothermia following trauma has been introduced in
      several studies to reduce the posttraumatic inflammation and organ injury. In
      this study, we analyzed the effects of induced mild hypothermia (34 degrees C) on
      the inflammation of the shock organs liver and kidney. METHODS: In a porcine
      model of multiple trauma including blunt chest trauma, liver laceration, and
      hemorrhagic shock followed by fluid resuscitation, the influence of induced
      hypothermia on hepatic and renal damage and organ-specific inflammation were
      evaluated. A total of 40 pigs were randomly assigned to four groups, which were
      sham (anesthesia only) or trauma groups receiving either hypothermia or
      normothermia. The parameters analyzed were laboratory parameters (aspartate
      transaminase [AST], lactate dehydrogenase, urea, creatinine) as well as hepatic
      and renal cytokine expression determined by real-time polymerase chain reaction
      (interleukin 6 [IL-6], IL-8). Blinded analysis of histologic changes in the liver
      and kidney was performed. RESULTS: Fifteen and a half hours following combined
      trauma, hepatic cytokine expression and liver damage were significantly increased
      in animals with normothermia compared with the respective sham group.
      Hypothermia, however, resulted in a fivefold reduced hepatic expression of IL-8
      (mean +/- SE, 2.4 +/- 1.3; p = 0.01) when compared with the normothermic trauma
      group (IL-8, 12.8 +/- 4.7). Accordingly, granulocyte infiltration and a
      histologic, semiquantitative score for liver injury were significantly higher in
      the normothermic trauma group. Serum AST levels raised significantly after trauma
      and normothermia compared with the respective sham group, while AST levels showed
      no difference from the sham groups in the hypothermic trauma group. In contrast,
      neither trauma nor hypothermia influenced the expression of IL-6 and IL-8 and
      tissue injury in the kidney. CONCLUSION: Therapeutic hypothermia seems to
      attenuate the hepatic inflammatory response and the associated liver injury after
      severe trauma. Therefore, induced hypothermia might represent a potential
      therapeutic strategy to avoid posttraumatic organ dysfunction.

PMID- 24854312
TI  - In-hospital mortality from femoral shaft fracture depends on the initial delay to
      fracture fixation and Injury Severity Score: a retrospective cohort study from
      the NTDB 2002-2006.
AB  - BACKGROUND: Optimal surgical timing for definitive treatment of femur fractures
      in severely injured patients remains controversial. This study was performed to
      examine in-hospital mortality for patients with femur fractures with regard to
      surgical timing, Injury Severity Score (ISS), and age. METHODS: The National
      Trauma Data Bank version 7.0 was used to evaluate in-hospital mortality for
      patients presenting with unilateral femur fractures. Patients were stratified
      into four groups by surgical timing (ST) and four groups by ISS. chi tests were
      used to evaluate baseline interrelationships. Binary regression was used to
      examine the association between time to surgery, ISS score, age, and mortality
      after adjusting for patient medical comorbidities, and personal demographics.
      RESULTS: A total of 7,540 patients met inclusion criteria, with a 1.4% overall in
      hospital mortality rate. For patients with an isolated femur fracture, surgical
      delay beyond 48 hours was associated with nearly five times greater mortality
      risk compared with surgery within 12 hours (adjusted relative risk, 4.8; 95%
      confidence interval, 1.6-14.1). Only severely injured patients (ISS, 26+) had
      higher associated mortality with no delay in surgical fixation (ST1 < 12 hours)
      relative to ST2 of 13 hours to 24 hours with an adjusted relative risk of 4.2
      (95% confidence interval, 1.0-16.7). The association between higher mortality
      rates and surgical delay beyond 48 hours was even stronger in the elderly
      patients. CONCLUSION: This study supports the work of previous authors who
      reported that early definitive fixation of femur fractures is not only
      beneficial, particularly in the elderly, but also consistent with more recent
      studies recommending at least 12-hour to 24-hour delay in fixation in severely
      injured patients to promote better resuscitation. LEVEL OF EVIDENCE: Therapeutic
      study, level III.

PMID- 24854313
TI  - Risk of thoracic injury from direct steering wheel impact in frontal crashes.
AB  - BACKGROUND: The combination of airbag and seat belt is considered to be the most
      effective vehicle safety system. However, despite the widespread availability of
      airbags and a belt use rate of more than 85%, US drivers involved in crashes
      continue to be at risk of serious thoracic injury. The objective of this study
      was to determine the influence of steering wheel deformation on driver injury
      risk in frontal automobile crash. METHODS: The analysis is based on cases
      extracted from the National Automotive Sampling System Crashworthiness Data
      System database for case years 1993 to 2011. The approach was to compare the
      adjusted odds of frontal crash injury experienced by drivers in vehicles with and
      without steering wheel deformation. RESULTS: Among frontal crash cases with
      belted drivers, observable steering wheel deformation occurred in less than 4% of
      all cases but accounted for 30% of belted drivers with serious (Abbreviated
      Injury Scale [AIS] score, 3+) thoracic injuries. Similarly, steering wheel
      deformation occurred in approximately 13% of unbelted drivers but accounted for
      60% of unbelted drivers with serious thoracic injuries. Belted drivers in frontal
      crashes with steering wheel deformation were found to have two times greater odds
      of serious thoracic injury. Unbelted drivers were found to have four times
      greater odds of serious thoracic injury in crashes with steering wheel
      deformation. In frontal crashes, steering wheel deformation was more likely to
      occur in unbelted drivers than belted drivers, as well as higher severity crashes
      and with heavier drivers. CONCLUSION: The results of the present study show that
      airbag deployment and seat belt restraint do not completely eliminate the
      possibility of steering wheel contact. Even with the most advanced restraint
      systems, there remains an opportunity for further reduction in thoracic injury by
      continued enhancement to the seat belt and airbag systems. Furthermore, the
      results showed that steering wheel deformation is an indicator of potential
      serious thoracic injury and can be useful to prehospital personnel in improving
      the diagnosis of serious injuries. LEVEL OF EVIDENCE: Prognostic study, level
      III.

PMID- 24854315
TI  - Implementation of a nationwide trauma network for the care of severely injured
      patients.
AB  - BACKGROUND: Regional differences in the care of severely injured patients remain
      problematic in industrial countries. METHODS: In 2006, the German Society for
      Trauma Surgery initiated the foundation of regional networks between trauma
      centers in a TraumaNetwork (TNW). The TNW consisted of five major elements as
      follows: (a) a whitebook on the treatment of severely injured patients; (b)
      evidence-based guidelines (S3); (c) local audits; (d) contracts of interhospital
      cooperation among all participating hospitals; and (e) TraumaRegister
      documentation. TNW hospitals are classified according to local audit results as
      supraregional (STC), regional (RTC), or local (LTC) trauma centers by criteria
      concerning staff, equipment, admission capacity, and responsibility. RESULTS:
      Five hundred four German trauma centers (TCs) were certified by the end of
      December 2012. By then, 37 regional TNWs, with a mean of 13.6 TCs, were
      established, covering approximately 80% of the country's territory. Of the
      hospitals, 92 were acknowledged as STCs, 210 as RTCs, and 202 as LTCs.In 2012,
      19,124 patients were documented by the certified TCs. Fifty-seven percent of the
      patients were treated in STCs, 34% in RTCs, and 9% in LTCs. The mean (SD) Injury
      Severity Score (ISS) was highest in STCs (21 [13]), compared with 18 (12) in RTCs
      and 16 (10) in LTCs. There were differences in expected mortality (based on
      Revised Injury Severity Classification) according to the differences in the
      severity of trauma among the different categories, but in all types, the expected
      mortality was significantly higher than the observed mortality (differences in
      STCs, 1.8%; RTCs, 1.4%; LTCs, 2.0%). CONCLUSION: According to our findings, it is
      possible to successfully structure and standardize the care of severely injured
      patients in a nationwide trauma system. Better outcomes than expected were
      observed in all categories of TNW hospitals. LEVEL OF EVIDENCE: Epidemiologic
      study, level III. Therapeutic/care management study, level IV.

PMID- 24854316
TI  - Update on the status and future of acute care surgery: 10 years later.
AB  - BACKGROUND: Ten years ago, the specialty of trauma surgery was considered to be
      in crisis. Since then, the Eastern Association for the Surgery of Trauma (EAST)
      created a position paper, and acute care surgery (ACS) has matured. A repeat
      survey of EAST members is indicated to evaluate the progress of ACS. METHODS: A
      survey was e-mailed to EAST members. Results were evaluated and compared with the
      previous position paper and survey. RESULTS: The response rate was 15%. More than
      three fourths of the respondents were male, and just less than one fourth of them
      were female. More than half of the respondents were in practice for less than 10
      years. Seventy-three percent were involved in research, although only 16% were
      allotted protected time. Most respondents felt that reimbursement for their
      effort was inadequate: 54% thought reimbursement was fair for trauma care, 59%
      for critical care, 49% for nontrauma ACS, and 62% for general surgery. The
      biggest incentive to a career in ACS was that it was a challenging and exciting
      activity; the biggest disincentive was working at night. Seventy-two percent
      expressed satisfaction with their career profile, and 92% were either very or
      somewhat happy with their career. Sixty-six percent did feel either somewhat or
      very burned out. Surgeons were interested in learning more about contract
      negotiation, business/managerial issues, and billing/coding. Compared with the
      previous survey, overall career satisfaction seems stable. CONCLUSION: Most
      surgeons are satisfied with a career in ACS. There are still some facets of the
      career that warrant improvement. Focus on surgeon satisfaction may lead to
      enhancements in patient care.

PMID- 24854314
TI  - Blood alcohol content, injury severity, and adult respiratory distress syndrome.
AB  - BACKGROUND: Elevated blood alcohol content (BAC) is a risk factor for injury.
      Associations of BAC with adult respiratory distress syndrome (ARDS) have not been
      conclusively established.We evaluated the association of a BAC greater than 0
      mg/dL with the intermediate outcomes, Injury Severity Score (ISS) and Glasgow
      Coma Scale (GCS) score, and their association with ARDS development. METHODS:
      This is an observational retrospective cohort study of 26,305 primary trauma
      admissions to a statewide referral trauma center from July 11, 2003, to October
      31, 2011. Logistic regression was performed to assess the relationship between
      admission BAC, ISS, GCS score, and ARDS development within 5 days of admission.
      RESULTS: The case rate for ARDS was 5.5% (1,447). BAC greater than 0 mg/dL was
      associated with ARDS development in adjusted analysis (odds ratio, 1.50; 95%
      confidence interval [CI], 1.33-1.71; p < 0.001). High ISS (>=16) had a stronger
      association with ARDS development (odds ratio, 17.99; 95% CI, 15.51-20.86), as
      did low GCS score (<=8) (odds ratio, 8.77; 95% CI, 7.64-10.07; p < 0.001).
      Patients with low GCS score and high ISS had the most frequent ARDS (33.6%) and
      the highest case-fatality rate without ARDS (24.7%). CONCLUSION: Elevated BAC is
      associated with ARDS development. In the analysis of alcohol exposure, ISS and
      GCS score occur after alcohol ingestion, making them intermediate outcomes. ISS
      and GCS score were strong predictors of ARDS and may be useful to identify at
      risk patients. Elevated BAC may increase the frequency of the ARDS through
      influence on injury severity or independent molecular mechanisms, which can be
      discriminated only in experimental models. LEVEL OF EVIDENCE: Epidemiologic
      study, level III.

PMID- 24854317
TI  - A composite index for predicting readmission following emergency general surgery.
AB  - BACKGROUND: Preventable readmission has become a national focus. It is clear that
      surgical patients present specific challenges to those interested in preventing
      readmission. Little is known about this outcome in the emergent population. We
      are interested in determining if there are readily available data variables to
      predict risk of readmission. The surgical Apgar score (SAS) is calculated from
      objective intraoperative variables and has been shown to be predictive of
      postoperative mortality in the nonemergent setting. The objectives of this study
      were to characterize 30-day readmissions in emergent general surgery and to
      determine whether certain variables were associated with readmissions. We
      hypothesized that the SAS correlates with the risk for readmission in emergency
      general surgery patients. PATIENTS AND METHODS: Variables of interest were
      obtained from a retrospective analysis of the American College of Surgeons'
      National Surgical Quality Improvement Program database at an academic
      institution, paired with the electronic medical record. We identified adult
      general surgery patients who underwent an emergency procedure from 2006 to 2012.
      Univariate analysis identified factors associated with 30-day readmission.
      Factors with p < 0.1 were included in the multivariate analysis to reveal
      potential risk factors. SPSS version 20 was used for the statistical analysis,
      with p < 0.05 considered to be significant on multivariate analysis. RESULTS: As
      compared with nonemergency surgery patients, emergency surgery patients had a
      higher readmission rate (11.1% vs. 15.2%, p = 0.004). The SAS (odds ratio, 3.297;
      95% confidence interval, 1.074-10.121; p = 0.037) and the combined variable of
      the American Society of Anesthesiologists Physical Status Classification and
      length of stay (odds ratio, 4.370; 95% confidence interval, 2.251-8.486; p <
      0.001) were associated with elevated risk for readmission in emergency general
      surgery patients. CONCLUSION: We have identified readily available measures that
      allow for the stratification of patients into low- and high-risk groups for 30
      day readmission. The stratification of patients will enable the study of
      prospective interventions designed to decrease unplanned readmissions in
      emergency surgery patients. LEVEL OF EVIDENCE: Prognostic study, level II.

PMID- 24854318
TI  - Improving organ donation rates by modifying the family approach process.
AB  - BACKGROUND: The purpose of this study was to identify steps during family
      approach for organ donation that may be modified to improve consent rates of
      potential organ donors. METHODS: Retrospective study of our local organ
      procurement organization (OPO) database of potential organ donors. Modifiable
      variables involved in the family approach of potential organ donors were
      collected and included race and sex of OPO representative, individual initiating
      approach discussion with family (RN or MD vs. OPO), length of donation
      discussion, use of a translator, and time of day of approach. RESULTS: Of 1137
      potential organ donors, 661 (58%) consented and 476 (42%) declined. Consent rates
      were higher with matched race of donor and OPO representative (66% vs. 52%, p <
      0.001), family approach by female OPO representative (67% vs. 56%, p = 0.002), if
      approach was initiated by OPO representative (69% vs. 49%, p < 0.001), and if
      consent rate was dependent on time of day the approach occurred: 6:00 am to noon
      (56%), noon to 6:00 pm (67%), 6:00 pm to midnight (68%), and midnight to 6:00 am
      (45%), p = 0.04. Family approach that led to consent lasted longer than those
      declining (67 vs. 43 minutes, p < 0.001). Independent predictors of consent to
      donation included female OPO representative (odds ratio [OR], 1.7; p = 0.006),
      approach discussion initiated by OPO representative (OR, 1.9; p = 0.001), and
      longer approach discussions (OR, 1.02; p < 0.001). The independent predictor of
      declined donation was the use of a translator (OR, 0.39; p = 0.01). CONCLUSION:
      Variables such as race and sex of OPO representative and time of day should be
      considered before approaching a family for organ donation. Avoiding translators
      during the approach process may improve donation rates. Education for health care
      providers should reinforce the importance of allowing OPO representatives to
      initiate the family approach for organ donation. LEVEL OF EVIDENCE: Epidemiologic
      study, level IV. Therapeutic study, level IV.

PMID- 24854319
TI  - Evaluation of the performance of French physician-staffed emergency medical
      service in the triage of major trauma patients.
AB  - BACKGROUND: Proper prehospital triage of trauma patients is a cornerstone for the
      process of care of trauma patients. In France, emergency physicians perform this
      process according to a national triage algorithm called Vittel Triage Criteria
      (VTC), introduced in 2002 to help the triage decision-making process. The aim of
      this two-center study was to evaluate the performance of the triage process based
      on the VTC to identify major trauma patients in the Paris area. METHODS: This was
      a retrospective analysis of two cohorts. The first cohort consisted of all
      patients admitted between January 2011 and September 2012 in two trauma referral
      centers in the region of Paris (Ile de France) and allowed estimation of
      overtriage. Undertriage was assessed in a second cohort made up of all
      prehospital trauma interventions from one emergency medicine sector during the
      same period. Adequate triage was defined by a direct admission of patients with
      an Injury Severity Score (ISS) greater than 15 into one of the regional trauma
      centers, and undertriage was defined as an initial nonadmission to a trauma
      center. Overtriage was defined by an admission of patients with an ISS of 15 or
      lower to a trauma center. The performance of the VTC was evaluated according to a
      strict to-the-letter application of the VTC and termed as theoretical triage.
      Logistic regression was performed to identify VTC criteria able to predict major
      trauma. RESULTS: Among 998 admitted patients of the first cohort, 173 patients
      (17%) were excluded because they were not directly admitted in the first 24
      hours. In the first cohort (n = 825), adequate triage was 58% and overtriage was
      42%. In the second cohort (n = 190), adequate triage was 40%, overtriage was 60%,
      and undertriage was less than 1%. Theoretical triage generated a nonsignificantly
      lower overtriage and a higher undertriage compared with observed triage. The most
      powerful predictors of major trauma were paralysis (odds ratio [OR,] 0.09; 95%
      confidence interval [CI], 0.03-0.22), flail chest (OR, 0.1; 95% CI, 0.01-0.03),
      and Glasgow Coma Scale (GCS) score of less than 13 (OR, 0.28; 95% CI, 0.17-0.45),
      whereas global assessments of speed and mechanism alone were poor predictors
      (positive likelihood ratio, 0.92-1.4). CONCLUSION: In the Paris area, the French
      physician-based prehospital triage system for patients with suspicion of major
      trauma showed a high rate of overtriage and a low rate of undertriage. Criteria
      of global assessment of speed and mechanism alone were poor predictors of major
      trauma.

PMID- 24854320
TI  - Timing and type of surgical treatment of Clostridium difficile-associated
      disease: a practice management guideline from the Eastern Association for the
      Surgery of Trauma.
AB  - BACKGROUND: Clostridium difficile infection is the leading cause of nosocomial
      diarrhea in the United States; however, few patients will develop fulminant C.
      difficile-associated disease (CDAD), necessitating an urgent operative
      intervention. Mortality for patients who require operative intervention is very
      high, up to 80% in some series. Since there is no consensus in the literature
      regarding the best operative treatment for this disease, we sought to answer the
      following:PICO [population, intervention, comparison, and outcome] Question 1: In
      adult patients with CDAD, does early surgery compared with late surgery, as
      defined by the need for vasopressors, decrease mortality?PICO Question 2: In
      adult patients with CDAD, does total abdominal colectomy (TAC) compared with
      other types of surgical intervention decrease mortality? METHODS: A subcommittee
      of the Practice Management Guideline Committee of the Eastern Association for the
      Surgery of Trauma conducted a systematic review and meta-analysis for the
      selected questions. RevMan software was used to generate forest plots. Grading of
      Recommendations, Assessment, Development and Evaluations methodology was used to
      rate the quality of the evidence, using GRADEpro software to create evidence
      tables. RESULTS: Reduction in mortality was significantly associated with early
      surgery, with a risk ratio (RR) of 0.5 (95% confidence interval [CI], 0.35-0.72).
      The quality of evidence was rated "moderate." Considering only the first
      procedure performed, mortality seemed to trend higher for TAC, with an RR of 1.11
      (95% CI, 0.69-1.80). Considering only the actual procedure performed, the point
      estimate switched sides, showing a trend toward decreased mortality with TAC (RR,
      0.86; 95% CI, 0.56-1.31). The quality of evidence was rated "very low."
      CONCLUSION: We strongly recommend that adult patients with CDAD undergo early
      surgery, before the development of shock and need for vasopressors. We
      conditionally recommend total or subtotal colectomy (vs. partial colectomy or
      other surgery) when the diagnosis of The Centers for Disease Control and
      Prevention is known.

PMID- 24854321
TI  - Animal models to assess the local and systemic effects of nailing: review of the
      literature and considerations for future studies.
AB  - BACKGROUND: Numerous experimental studies have been performed to investigate the
      adverse effects of reamed versus unreamed nailing in isolated or combined trauma
      models. However, the translational relevance is still discussed controversially.
      METHODS AND RESULTS: A systemic review of the literature was performed. An
      increase of intramedullary pressure with liberation of emboli to the venous and
      systemic circulation associated with reamed and unreamed nailing has been well
      described. Reamed nailing, however, seems to have superior clinical results in
      terms of fracture healing. CONCLUSION: The pathophysiologic effects, optimal
      timing, and technique of reamed nailing particularly in patients with multiple
      injuries continue to be controversial topics. Therefore, further experimental
      studies should focus on these topics as well as on the interaction of local and
      systemic processes particularly in the context of different surgical treatment
      strategies (Early Total Care vs. Damage Control Orthopaedics) to improve our
      understanding and approach to intramedullary nailing.

PMID- 24854322
TI  - Critical care responsibility in health care reform: what would Osler say?

PMID- 24854325
TI  - Surface modification of poly(styrene-b-(ethylene-co-butylene)-b-styrene) (SEBS)
      elastomer via covalent immobilization of nonionic sugar-based Gemini surfactants.
AB  - Gemini surfactants (GS) with sugar-containing head-groups and different alkyl
      chains were successfully prepared. Poly(styrene-b-(ethylene-co-butylene)-b
      styrene) (SEBS) elastomer was grafted with glycidyl methacrylate (GMA) by means
      of UV-induced graft polymerization, and then the pGMA-grafted film was chemically
      immobilized with the GS. The surface graft polymerization was confirmed by ATR
      FTIR and XPS. The wettability and hemocompatibility of the modified surface were
      characterized by means of water contact angle, protein adsorption, and platelet
      adhesion assays. The results showed that amphiphilic surfactant-containing
      polymer surfaces presented protein-resistant behavior and anti-platelet adhesion
      after functionalization with GS, GS1 and GS2. Besides, the hemocompatibility of
      the modified surface deteriorated as the length of hydrophobic chain of GS
      increased.

PMID- 24854326
TI  - Effects of professional oral health care on reducing the risk of chemotherapy
      induced oral mucositis.
AB  - PURPOSE: Recent years have seen remarkable progress in cancer therapy, although
      treatment-induced adverse reactions and complications are not uncommon.
      Approximately 40 % of patients undergoing chemotherapy for cancer experience
      adverse reactions in the oral cavity, with nearly half of them developing severe
      oral mucositis that necessitates postponing therapy and/or changing the drug
      dosage. The objective of this study was to assess the usefulness of prophylactic
      professional oral health care (POHC) for preventing mucositis in patients
      undergoing chemotherapy. METHODS: Twenty-six female patients scheduled for
      chemotherapy for breast cancer were included in this study and randomized to the
      self-care or POHC groups. Assessment parameters included oral cavity photographs,
      plaque control records, Saxon test scores, Oral Assessment Guide scores, and
      grading using the Common Terminology Criteria for Adverse Events. Beginning
      before surgery and continuing through the completion of chemotherapy, the POHC
      patient group received weekly professional oral health care, including scaling,
      professional cleaning of the tooth surfaces, brushing instructions, and
      nutritional and lifestyle guidance. RESULTS: More patients in the self-care group
      developed oral mucositis than in the POHC group. The Oral Assessment Guide score,
      which was used as an index of oral mucositis, was also significantly lower in the
      POHC group. Based on the Oral Assessment Guide and plaque control records, there
      was almost no deterioration of the oral environment in the POHC group, whereas
      deterioration was observed in the self-care group. CONCLUSIONS: These findings
      demonstrate the efficacy of regular POHC in reducing the risk of oral mucositis
      in breast cancer patients undergoing chemotherapy.

PMID- 24854328
TI  - Simple hydraulic conductivity estimation by the Kalman filtered double constraint
      method.
AB  - This paper presents the Kalman Filtered Double Constraint Method (DCM-KF) as a
      technique to estimate the hydraulic conductivities in the grid blocks of a
      groundwater flow model. The DCM is based on two forward runs with the same
      initial grid block conductivities, but with alternating flux-head conditions
      specified on parts of the boundary and the wells. These two runs are defined as:
      (1) the flux run, with specified fluxes (recharge and well abstractions), and (2)
      the head run, with specified heads (measured in piezometers). Conductivities are
      then estimated as the initial conductivities multiplied by the fluxes obtained
      from the flux run and divided by the fluxes obtained from the head run. The DCM
      is easy to implement in combination with existing models (e.g., MODFLOW).
      Sufficiently accurate conductivities are obtained after a few iterations. Because
      of errors in the specified head-flux couples, repeated estimation under varying
      hydrological conditions results in different conductivities. A time-independent
      estimate of the conductivities and their inaccuracy can be obtained by a simple
      linear KF with modest computational requirements. For the Kleine Nete catchment,
      Belgium, the DCM-KF yields sufficiently accurate calibrated conductivities. The
      method also results in distinguishing regions where the head-flux observations
      influence the calibration from areas where it is not able to influence the
      hydraulic conductivity. 

PMID- 24854330
TI  - A longitudinal examination of the relation between parental expressed emotion and
      externalizing behaviors in children and adolescents with autism spectrum
      disorder.
AB  - The current study explored the longitudinal relation between parental expressed
      emotion, a well-established predictor of symptom relapse in various other
      disorders (e.g., schizophrenia) with externalizing behaviors in 84 children, ages
      8-18 (at Time 2), with autism spectrum disorder (ASD). It was found that parental
      expressed emotion, specifically criticism/hostility at Time 1, significantly
      related to a change in externalizing behaviors from Time 1 to Time 2, even after
      controlling for Time 1 family income, ASD symptom severity, parental distress,
      and parenting practices. That is, higher levels of parental criticism/hostility
      at Time 1 predicted higher levels of child externalizing behaviors at Time 2.
      However, the reverse was not found. This finding of a unidirectional relation has
      important clinical implications. 

PMID- 24854331
TI  - Brief report: parent-child sexuality communication and autism spectrum disorders.
AB  - While considerable research has focused on promoting independence and optimizing
      quality of life for adolescents and young adult with autism spectrum disorder
      (ASD), sexual development and sexuality education have been largely neglected.
      Experts recommend that parents be the primary source of sex education for
      adolescents with ASD, and that sex education be tailored to a child's
      developmental level. Prior studies show that parents of youth with ASD are
      uncertain about how to best communicate about sex and which topics to discuss
      with their children. In the current study we administered an online survey to 190
      parents of adolescents with ASD in order to better understand sexuality
      communication patterns between parents and adolescents with both low and high
      functioning ASD. 

PMID- 24854329
TI  - Cannabidiol: pharmacology and potential therapeutic role in epilepsy and other
      neuropsychiatric disorders.
AB  - To present a summary of current scientific evidence about the cannabinoid,
      cannabidiol (CBD) with regard to its relevance to epilepsy and other selected
      neuropsychiatric disorders. We summarize the presentations from a conference in
      which invited participants reviewed relevant aspects of the physiology,
      mechanisms of action, pharmacology, and data from studies with animal models and
      human subjects. Cannabis has been used to treat disease since ancient times.
      Delta(9) -Tetrahydrocannabinol (Delta(9) -THC) is the major psychoactive
      ingredient and CBD is the major nonpsychoactive ingredient in cannabis. Cannabis
      and Delta(9) -THC are anticonvulsant in most animal models but can be
      proconvulsant in some healthy animals. The psychotropic effects of Delta(9) -THC
      limit tolerability. CBD is anticonvulsant in many acute animal models, but there
      are limited data in chronic models. The antiepileptic mechanisms of CBD are not
      known, but may include effects on the equilibrative nucleoside transporter; the
      orphan G-protein-coupled receptor GPR55; the transient receptor potential of
      vanilloid type-1 channel; the 5-HT1a receptor; and the alpha3 and alpha1 glycine
      receptors. CBD has neuroprotective and antiinflammatory effects, and it appears
      to be well tolerated in humans, but small and methodologically limited studies of
      CBD in human epilepsy have been inconclusive. More recent anecdotal reports of
      high-ratio CBD:Delta(9) -THC medical marijuana have claimed efficacy, but studies
      were not controlled. CBD bears investigation in epilepsy and other
      neuropsychiatric disorders, including anxiety, schizophrenia, addiction, and
      neonatal hypoxic-ischemic encephalopathy. However, we lack data from well-powered
      double-blind randomized, controlled studies on the efficacy of pure CBD for any
      disorder. Initial dose-tolerability and double-blind randomized, controlled
      studies focusing on target intractable epilepsy populations such as patients with
      Dravet and Lennox-Gastaut syndromes are being planned. Trials in other treatment
      resistant epilepsies may also be warranted. A PowerPoint slide summarizing this
      article is available for download in the Supporting Information section here. 

PMID- 24854332
TI  - Detection of opsonic antibodies against Enterococcus faecalis cell wall
      carbohydrates in immune globulin preparations.
AB  - Three different commercially available polyvalent immune globulins (IG) were
      investigated for the existence of antibodies against cell wall carbohydrates of
      four different E. faecalis serotypes (using a cell wall carbohydrate-enzyme
      linked immunosorbent assay), and whether these antibodies mediated opsonic
      killing (using an opsonic-killing assay). All three IG preparations contained
      antibodies against all four serotypes (CPS-A to CPS-D). However, only one of the
      three IG preparations showed opsonic killing against all four serotypes. Average
      killing was higher against serotypes A and B (72 and 79 %, respectively) than
      against serotypes C and D (30 and 37 %, respectively). Such IG preparations could
      play a role as an adjuvant therapeutic option in life-threatening infections with
      E. faecalis, particularly when resistant strains are involved.

PMID- 24854336
TI  - Clinical relevance of cagL gene and virulence genotypes with disease outcomes in
      a Helicobacter pylori infected population from Iran.
AB  - Helicobacter pylori infection is common in Iran as in other developing countries.
      Certain genotypes of H. pylori have been associated with increased occurrence of
      chronic gastritis, peptic ulcers, and gastric adenocarcinoma. The aim of this
      study was to investigate the clinical relevance of cagL gene and other virulence
      genotypes of H. pylori isolates with clinical outcomes in Iranian patients.
      Totally, 126 symptomatic patients who underwent gastroduodenal endoscopy were
      enrolled in the study. Sixty-one H. pylori strains were isolated from the
      patients studied. The presence of the cagL, cagA, vacA, iceA, babA2 and sabA
      genes in the corresponding H. pylori isolates were determined by polymerase chain
      reaction and the results were compared with clinical outcomes and histopathology.
      The cagL, cagA, vacA s1, vacA s2, vacA m1, vacA m2, iceA1, iceA2, babA 2 , and
      sabA genotypes were detected in 96.7, 85.2, 75.4, 24.6, 29.5, 70.5, 42.6, 23,
      96.7, and 83.6% of the isolates, respectively. The three genotypic combinations,
      cagL/cagA/vacAs1m1/iceA1/babA2/sabA, cagL/cagA/vacAs1m2/iceA1/babA2/sabA, and
      cagL/cagA/vacAs1m2/iceA2/babA2/sabA were determined as the most prevalent
      combined genotypes. There was a significant correlation between the presence of
      cagL gene and cagA positivity (P = 0.02). No significant correlation was found
      between the various genotypes and clinical outcomes (P > 0.05). The present study
      showed a very high prevalence of cagL genotype among the H. pylori isolates from
      Iranian patients. Our results demonstrated that neither single genotype nor
      combination genotypes of virulence-associated genes was significantly helpful
      markers for predicting the severity of gastroduodenal disease associated with H.
      pylori infection in Iranian patients.

PMID- 24854338
TI  - Quality failures in residential aged care in Australia: The relationship between
      structural factors and regulation imposed sanctions.
AB  - AIM: To examine the relationship between structural factors and the imposition of
      sanctions on residential aged care services across Australia for regulatory
      compliance failure. METHODS: Poisson Regression analysis was used to examine the
      association between the number of sanctions imposed and the structural
      characteristics of residential aged care services in Australia. RESULTS:
      Residential aged care services that have a greater likelihood of having
      government sanctions imposed on them are operated by for-profit providers and
      located in remote locations and in Victoria, Queensland, South Australia,
      Northern Territory and the Australian Capital Territory. CONCLUSION: The findings
      confirm the international literature on the relationship between residential aged
      care service location, ownership type and the likelihood of sanctions. In the
      light of the predicted expansion of residential aged care services, policy makers
      should give consideration to structural elements most likely to be associated
      with a failure to meet and maintain service standards.

PMID- 24854337
TI  - Dynamic functional modulation of CD4+ T cell recall responses is dependent on the
      inflammatory environment of the secondary stimulus.
AB  - The parameters that modulate the functional capacity of secondary Th1 effector
      cells are poorly understood. In this study, we employ a serial adoptive transfer
      model system to show that the functional differentiation and secondary memory
      potential of secondary CD4+ effector T cells are dependent on the inflammatory
      environment of the secondary challenge. Adoptive transfer of TCR transgenic
      lymphocytic choriomeningitis virus (LCMV) Glycoprotein-specific SMARTA memory
      cells into LCMV-immune hosts, followed by secondary challenge with Listeria
      monocytogenes recombinantly expressing a portion of the LCMV Glycoprotein (Lm
      gp61), resulted in the rapid emergence of SMARTA secondary effector cells with
      heightened functional avidity (as measured by their ability to make IFNgamma in
      response to ex vivo restimulation with decreasing concentrations of peptide),
      limited contraction after pathogen clearance and stable maintenance secondary
      memory T cell populations. In contrast, transfer of SMARTA memory cells into
      naive hosts prior to secondary Lm-gp61 challenge, which resulted in a more
      extended infectious period, resulted in poor functional avidity, increased death
      during the contraction phase and poor maintenance of secondary memory T cell
      populations. The modulation of functional avidity during the secondary Th1
      response was independent of differences in antigen load or persistence. Instead,
      the inflammatory environment strongly influenced the function of the secondary
      Th1 response, as inhibition of IL-12 or IFN-I activity respectively reduced or
      increased the functional avidity of secondary SMARTA effector cells following
      rechallenge in a naive secondary hosts. Our findings demonstrate that secondary
      effector T cells exhibit inflammation-dependent differences in functional avidity
      and memory potential, and have direct bearing on the design of strategies aimed
      at boosting memory T cell responses. 

PMID- 24854342
TI  - Improving photoprotection: 4-methylbenzylidene camphor microspheres.
AB  - Abstract We propose a new approach for photoprotection. 4-Methylbenzylidene
      camphor (4-MBC), one of the most widely used UV filters, was encapsulated in
      microspheres, with a view to overcoming problems (percutaneous absorption,
      photodegradation and lack of lasting effect) arising with organic sunscreens, and
      to achieve safe photoprotection. We focused on this filter in the light of the
      Cosmetics Europe opinion concerning its possible effects on the thyroid gland.
      Microspheres were prepared by emulsification-solvent evaporation, using different
      amounts of 4-MBC and characterized for morphology, encapsulation efficiency and
      particle size. The particles were then mixed in O/W emulsions. The in vitro sun
      protection factors, in vitro release and photostability were investigated and
      compared with emulsions containing the free sunscreen. The new microspheres offer
      good morphology and loading (up to 40%), and the same photoprotection as the free
      filter while at the same time protecting it from photodegradation. The systems
      also give a slower release from the emulsions.

PMID- 24854339
TI  - Are current atomistic force fields accurate enough to study proteins in crowded
      environments?
AB  - The high concentration of macromolecules in the crowded cellular interior
      influences different thermodynamic and kinetic properties of proteins, including
      their structural stabilities, intermolecular binding affinities and enzymatic
      rates. Moreover, various structural biology methods, such as NMR or different
      spectroscopies, typically involve samples with relatively high protein
      concentration. Due to large sampling requirements, however, the accuracy of
      classical molecular dynamics (MD) simulations in capturing protein behavior at
      high concentration still remains largely untested. Here, we use explicit-solvent
      MD simulations and a total of 6.4 us of simulated time to study wild-type
      (folded) and oxidatively damaged (unfolded) forms of villin headpiece at 6 mM and
      9.2 mM protein concentration. We first perform an exhaustive set of simulations
      with multiple protein molecules in the simulation box using GROMOS 45a3 and 54a7
      force fields together with different types of electrostatics treatment and
      solution ionic strengths. Surprisingly, the two villin headpiece variants exhibit
      similar aggregation behavior, despite the fact that their estimated aggregation
      propensities markedly differ. Importantly, regardless of the simulation protocol
      applied, wild-type villin headpiece consistently aggregates even under conditions
      at which it is experimentally known to be soluble. We demonstrate that
      aggregation is accompanied by a large decrease in the total potential energy,
      with not only hydrophobic, but also polar residues and backbone contributing
      substantially. The same effect is directly observed for two other major atomistic
      force fields (AMBER99SB-ILDN and CHARMM22-CMAP) as well as indirectly shown for
      additional two (AMBER94, OPLS-AAL), and is possibly due to a general
      overestimation of the potential energy of protein-protein interactions at the
      expense of water-water and water-protein interactions. Overall, our results
      suggest that current MD force fields may distort the picture of protein behavior
      in biologically relevant crowded environments. 

PMID- 24854341
TI  - Liver transplantation in recipients receiving renal replacement therapy: outcomes
      analysis and the role of intraoperative hemodialysis.
AB  - The Model for End-Stage Liver Disease (MELD) system has dramatically increased
      the number of recipients requiring pretransplant renal replacement therapy (RRT)
      prior to liver transplantation (LT). Factors affecting post-LT outcomes and the
      need for intraoperative RRT (IORRT) were analyzed in 500 consecutive recipients
      receiving pretransplant RRT, including comparisons among recipients not receiving
      IORRT (No-IORRT, n = 401), receiving planned IORRT (Pl-IORRT, n = 70), and
      receiving emergent, unplanned RRT after LT initiation (Em-IORRT, n = 29). Despite
      a median MELD of 39, overall 30-day, 1-, 3- and 5-year survivals were 93%, 75%,
      68% and 65%, respectively. Em-IORRT recipients had significantly more
      intraoperative complications (arrhythmias, postreperfusion syndrome,
      coagulopathy) compared with both No-IORRT and Pl-IORRT and greater 30-day graft
      loss (28% vs. 10%, p = 0.004) and need for retransplantation (24% vs. 10%, p =
      0.099) compared with No-IORRT. A risk score based on multivariate predictors of
      IORRT accurately identified recipients with chronic (sensitivity 84%, specificity
      72%, concordance-statistic [c-statistic] 0.829) and acute (sensitivity 93%,
      specificity 61%, c-statistic 0.776) liver failure requiring IORRT. In this
      largest experience of LT in recipients receiving RRT, we report excellent
      survival and propose a practical model that accurately identifies recipients who
      may benefit from IORRT. For this select group, timely initiation of IORRT reduces
      intraoperative complications and improves posttransplant outcomes. 

PMID- 24854340
TI  - Generation of induced pluripotent stem cell-derived mice by reprogramming of a
      mature NKT cell.
AB  - NKT cells are characterized by their expression of an NKT-cell-specific invariant
      antigen-receptor alpha chain encoded by Valpha14Jalpha18 gene segments. These NKT
      cells bridge the innate and acquired immune systems to mediate effective and
      augmented responses; however, the limited number of NKT cells in vivo hampers
      their analysis. Here, two lines of induced pluripotent stem cell-derived mice
      (NKT-iPSC-derived mice) were generated by reprogramming of mature NKT cells,
      where one harbors both rearranged Valpha14Jalpha18 and Vbeta7 genes and the other
      carries rearranged Valpha14Jalpha18 on both alleles but germline Vbeta loci. The
      analysis of NKT-iPSC-derived mice showed a significant increase in NKT cell
      numbers with relatively normal frequencies of functional subsets, but
      significantly enhanced in some cases, and acquired functional NKT cell maturation
      in peripheral lymphoid organs. NKT-iPSC-derived mice also showed normal
      development of other immune cells except for the absence of gammadeltaT cells and
      disturbed development of conventional CD4 alphabetaT cells. These results suggest
      that the NKT-iPSC-derived mice are a better model for NKT cell development and
      function study rather than transgenic mouse models reported previously and also
      that the presence of a pre-rearranged Valpha14Jalpha18 in the natural chromosomal
      context favors the developmental fate of NKT cells. 

PMID- 24854343
TI  - Nomenclature update and allele repeat structure for the markers DYS518 and
      DYS449.

PMID- 24854344
TI  - Remembering Mr B.
AB  - In the accompanying translation and film, Gustav Storring describes the
      psychological profile of Mr. B. (Franz Breundl), a victim of carbon monoxide
      poisoning with a nearly complete short-term memory deficit. Storring diagnoses
      Mr. B. as lacking entirely the capacity to register or retain any information in
      consciousness for longer than two seconds. Here we introduce these historical
      documents, describe their historical context, summarize and discuss the central
      features of the case, and consider the potential significance of the case for
      contemporary theories of working memory, the self, and personal identity. 

PMID- 24854345
TI  - PKG and NHR-49 signalling co-ordinately regulate short-term fasting-induced
      lysosomal lipid accumulation in C. elegans.
AB  - Lysosomes act as terminal degradation organelles to hydrolyse macromolecules
      derived from both the extracellular space and the cytoplasm. In Caenorhabditis
      elegans fasting induces the lysosomal compartment to expand. However, the
      molecular and cellular mechanisms for this stress response remain largely
      unclear. In the present study, we find that short-term fasting leads to increased
      accumulation of polar lipids in lysosomes. The fasting response is co-ordinately
      regulated by EGL-4, the C. elegans PKG (protein kinase G) orthologue, and nuclear
      hormone receptor NHR-49. Further results demonstrate that EGL-4 acts in sensory
      neurons to enhance lysosomal lipid accumulation through inhibiting the DAF-3/SMAD
      pathway, whereas NHR-49 acts in intestine to inhibit lipids accumulation via
      activation of IPLA-2 (intracellular membrane-associated calcium-independent
      phospholipase A2) in cytoplasm and other hydrolases in lysosomes. Remarkably, the
      lysosomal lipid accumulation is independent of autophagy and RAB-7-mediated
      endocytosis. Taken together, our results reveal a new mechanism for lysosomal
      lipid metabolism during the stress response, which may provide new clues for
      investigations of lysosome function in energy homoeostasis. 

PMID- 24854346
TI  - Enantiomeric separation of new cathinone derivatives designer drugs by capillary
      electrochromatography using a chiral stationary phase, based on amylose tris(5
      chloro-2-methylphenylcarbamate).
AB  - In this study, a chiral CEC method for the enantiomeric separation of ten
      cathinone derivatives, by means of a polysaccharide-based chiral stationary
      phase, has been developed. Capillary columns of 100 MUm id packed with amylose
      tris(5-chloro-2-methylphenylcarbamate) coated on silica, also called Sepapak 3 or
      Lux Amylose-2, were used to achieve the enantioseparation of the studied designer
      drugs. Enantioresolution, chromatographic retention, and separation efficiency
      were evaluated in dependence of mobile-phase composition in terms of the content
      of the organic modifier, nature, and pH buffer. To obtain a sensitivity
      improvement, a field-amplified sample injection was evaluated optimizing the
      sample solvent composition and injection time. The LODs and LOQs values were in
      the range 25-100 and 50-150 ng/mL, respectively, for all the racemic compounds.
      Good results in terms of resolution (Rs ), separation efficiency (N/m), and short
      analysis times were obtained using a mixture of ACN/methanol/sodium acetate pH 9
      (89/10/1, v/v/v). Applying a voltage of 10 kV and a temperature of 20 degrees C,
      the analyzed cathinone derivatives were separated in their enantiomers in less
      than 10 min. A study, concerning the method precision, in terms of intra- and
      interday repeatability and column-to-column reproducibility was carried out in
      accordance with the analytical procedures for method validation. Intra- and
      interday repeatability provided RSD values in the ranges 1.1-1.7, 1.3-2.3% for
      retention time and 1.3-2.6, 2.1-3.4% for peak area, respectively. 

PMID- 24854347
TI  - Vasogenic edema characterizes pediatric acute disseminated encephalomyelitis.
AB  - INTRODUCTION: MR imaging criteria for diagnosing acute disseminated
      encephalomyelitis (ADEM) have not been clearly established. Due to the wide
      spectrum of differential considerations, new imaging features allowing early and
      accurate diagnosis for ADEM are needed. We hypothesized that ADEM lesions would
      be characterized by vasogenic edema due to the potential reversibility of the
      disease. METHODS: Sixteen patients who met the diagnostic criteria for ADEM
      proposed by the International Pediatric Multiple Sclerosis Study Group (IPMSSG)
      and had complete MR imaging studies performed at our institution during the acute
      phase of the disease were identified retrospectively and evaluated by experienced
      pediatric neuroradiologists. RESULTS: Vasogenic edema was demonstrated on
      diffusion-weighted imaging (DWI) and corresponding apparent diffusion coefficient
      (ADC) maps in 12 out of 16 patients; cytotoxic edema was identified in two
      patients while the other two patients displayed no changes on DWI/ADC. ADC values
      for lesions and normal-appearing brain tissue were 1.39 +/- 0.45 * 10(-3) and
      0.81 +/- 0.09 * 10(-3) mm/s(2), respectively (p=0.002). When considering a cutoff
      of 5 days between acute and subacute disease, no difference between ADC values in
      acute vs. subacute phase was depicted. However, we found a significant
      correlation and an inverse and significant relationship between time and ADC
      value. CONCLUSION: We propose that vasogenic edema is a reliable diagnostic sign
      of acute neuroinflammation in ADEM.

PMID- 24854349
TI  - Utility of finger maze test for learning and memory abilities in infants of
      cynomolgus monkeys exposed to thiamazole.
AB  - A new type of learning and memory test using a finger maze was conducted in
      infant cynomolgus monkeys that were exposed to thiamazole (2 and 3.5 mg/kg per
      day to pregnant animals orally) during the fetal period (gestational days 120 to
      150). We modified Tsuchida's original finger maze test method by reducing the
      number of trials per day and simplifying the criteria for achievement of
      training, and we added a long-term memory test. In the memory test, thiamazole
      exposed infants required greater time to complete the finger maze test than the
      control infants although no effect was noted in the training or learning test.
      The results suggest that an impaired long-term memory could be detected by our
      modified finger maze test. 

PMID- 24854348
TI  - Central and midperipheral corneal thickness measured with Scheimpflug imaging and
      optical coherence tomography.
AB  - PURPOSE: To compare corneal thickness measurements using Pentacam (Oculus,
      Germany), Sirius (CSO, Italy), Galilei (Ziemer, Switzerland), and RTVue-100 OCT
      (Optovue Inc., USA). METHODS: Sixty-six eyes of 66 healthy volunteers were
      enrolled. Three consecutive measurements were performed with each device. The
      mean value of the three measurements was used for subsequent analysis. Central
      corneal thickness (CCT), thinnest corneal thickness (TCT), and midperipheral
      corneal thickness (MPCT; measured at superior, inferior, nasal, and temporal
      locations with a distance of 1 mm (CT2mm) or 2.5 mm (CT5mm) from the corneal
      apex) were analyzed. Differences and agreement between measurements were assessed
      using the repeated-measures analysis of variance (ANOVA) and Bland-Altman
      analyses, respectively. RESULTS: Statistically significant differences (p<0.001)
      among the four devices were revealed in CCT, TCT and CT2mm measurements. The CCT,
      TCT, and CT2mm values were ranked from the thickest to the thinnest as follows:
      Galilei>Sirius>Pentacam>RTVue OCT. For these measurements, agreement between
      measurements by Sirius and Pentacam was good, whereas Galilei overestimated and
      RTVue underestimated corneal thickness compared to Sirius and Pentacam. As
      regards CT5mm measurements, Pentacam provided the largest values, whereas RTVue
      OCT yielded the smallest values. Agreement of the CT5mm measurements was good
      between the Pentacam, Sirius, moderate between Galilei and the other two
      Scheimpflug systems, and poor between the RTVue OCT and the remaining devices.
      CONCLUSIONS: The Pentacam and Sirius can be used interchangeably for CCT
      measurements, while the Galilei and RTVue systematically over- and underestimate
      CCT, respectively. The three Scheimpflug cameras, but not the RTVue, may be used
      interchangeably for MPCT measurements.

PMID- 24854350
TI  - Sarcocystis nesbitti causes acute, relapsing febrile myositis with a high attack
      rate: description of a large outbreak of muscular sarcocystosis in Pangkor
      Island, Malaysia, 2012.
AB  - BACKGROUND: From the 17th to 19th January 2012, a group of 92 college students
      and teachers attended a retreat in a hotel located on Pangkor Island, off the
      west coast of Peninsular Malaysia. Following the onset of symptoms in many
      participants who presented to our institute, an investigation was undertaken
      which ultimately identified Sarcocystis nesbitti as the cause of this outbreak.
      METHODOLOGY/PRINCIPAL FINDINGS: All retreat participants were identified, and
      clinical and epidemiological information was obtained via clinical review and
      self-reported answers to a structured questionnaire. Laboratory, imaging and
      muscle biopsy results were evaluated and possible sources of exposure, in
      particular water supply, were investigated. At an average of 9-11 days upon
      return from the retreat, 89 (97%) of the participants became ill. A vast majority
      of 94% had fever with 57% of these persons experiencing relapsing fever. Myalgia
      was present in 91% of patients. Facial swelling from myositis of jaw muscles
      occurred in 9 (10%) patients. The median duration of symptoms was 17 days (IQR 7
      to 30 days; range 3 to 112). Out of 4 muscle biopsies, sarcocysts were identified
      in 3. S. nesbitti was identified by PCR in 3 of the 4 biopsies including one
      biopsy without observed sarcocyst. Non-Malaysians had a median duration of
      symptoms longer than that of Malaysians (27.5 days vs. 14 days, p = 0.001) and
      were more likely to experience moderate or severe myalgia compared to mild
      myalgia (83.3% vs. 40.0%, p = 0.002). CONCLUSIONS/SIGNIFICANCE: The similarity of
      the symptoms and clustered time of onset suggests that all affected persons had
      muscular sarcocystosis. This is the largest human outbreak of sarcocystosis ever
      reported, with the specific Sarcocystis species identified. The largely non
      specific clinical features of this illness suggest that S. nesbitti may be an
      under diagnosed infection in the tropics.

PMID- 24854351
TI  - Change in access to prescribed medication following an episode of deliberate self
      poisoning: a multilevel approach.
AB  - OBJECTIVE: Patients with a history of deliberate self-poisoning (DSP) are
      prescribed a greater amount of medication than the general public. DSP is the
      most robust risk factor for repeat episodes of DSP and subsequent death by
      suicide, and one might therefore expect that access to prescribed medication
      would be reduced following an episode of DSP. However, it is unclear whether
      access to prescribed medication changes after an episode of DSP. The objectives
      of this study were to investigate changes in 1) overall, psychotropic, non
      psychotropic and the psychotropic subgroup antidepressant prescribed medication
      availability in DSP patients following an episode of DSP, 2) prescribing of the
      medication ingested in the episode, and 3) potential effects of gender, age and
      repeater status on such change. METHODS: The design was longitudinal. We included
      171 patients admitted for DSP between January 2006 and March 2007. Data on
      patients' prescriptions prior to admission were retrieved from The Norwegian
      Prescription Database. The outcome measure was the difference between medication
      load in the year following compared to the year prior to the DSP episode.
      RESULTS: There was a significant increase in total medication load following DSP,
      including both psychotropic and non-psychotropic medication. Antidepressant
      medication load remained stable. There was a tendency for access to drugs
      ingested in the episode to increase following the episode, albeit not
      significantly. Medication load increased with age across all medication groups
      irrespective of time period and gender. CONCLUSIONS: The findings show that
      physicians do not curb prescribing to patients who have recently deliberately
      self-poisoned. Moreover, they highlight the need for cautious and judicious
      prescribing for these patients, in combination with psychological and social
      interventions.

PMID- 24854352
TI  - Strontium isotopes and the reconstruction of the Chaco regional system:
      evaluating uncertainty with Bayesian mixing models.
AB  - Strontium isotope sourcing has become a common and useful method for assigning
      sources to archaeological artifacts.In Chaco Canyon, an Ancestral Pueblo regional
      center in New Mexico, previous studiesusing these methods have suggested that
      significant portion of maize and wood originate in the Chuska Mountains region,
      75 km to the West [corrected]. In the present manuscript, these results were
      tested using both frequentist methods (to determine if geochemical sources can
      truly be differentiated) and Bayesian methods (to address uncertainty in
      geochemical source attribution). It was found that Chaco Canyon and the Chuska
      Mountain region are not easily distinguishable based on radiogenic strontium
      isotope values. The strontium profiles of many geochemical sources in the region
      overlap, making it difficult to definitively identify any one particular
      geochemical source for the canyon's pre-historic maize. Bayesian mixing models
      support the argument that some spruce and fir wood originated in the San Mateo
      Mountains, but that this cannot explain all 87Sr/86Sr values in Chaco timber.
      Overall radiogenic strontium isotope data do not clearly identify a single major
      geochemical source for maize, ponderosa, and most spruce/fir timber. As such, the
      degree to which Chaco Canyon relied upon outside support for both food and
      construction material is still ambiguous.

PMID- 24854353
TI  - Molecular analysis of the genes involved in aroma synthesis in the species S.
      cerevisiae, S. kudriavzevii and S. bayanus var. uvarum in winemaking conditions.
AB  - The Saccharomyces genus is the main yeast involved in wine fermentations to play
      a crucial role in the production and release of aromatic compounds. Despite the
      several studies done into the genome-wide expression analysis using DNA
      microarray technology in wine S. cerevisiae strains, this is the first to
      investigate other species of the Saccharomyces genus. This research work
      investigates the expression of the genes involved in flavor compound production
      in three different Saccharomyces species (S. cerevisiae, S. bayanus var. uvarum
      and S. kudriavzevii) under low (12 degrees C) and moderate fermentation
      temperatures (28 degrees C). The global genes analysis showed that 30% of genes
      appeared to be differently expressed in the three cryophilic strains if compared
      to the reference strain (mesophilic S. cerevisiae), suggesting a very close cold
      adaptation response. Remarkable differences in the gene expression level were
      observed when comparing the three species, S. cerevisiae, S. bayanus var. uvarum
      and S. kudriavzevii, which will result in different aroma profiles. Knowledge of
      these differences in the transcriptome can be a tool to help modulate aroma to
      create wines with the desired aromatic traits. 

PMID- 24854354
TI  - Frequent conversion of tuberculosis screening tests during anti-tumour necrosis
      factor therapy in patients with rheumatic diseases.
AB  - OBJECTIVES: To determine the rate of tuberculosis (TB) screening test conversion
      during anti-tumour necrosis factor (TNF) therapy in rheumatic patients with
      negative baseline screening. METHODS: This was a prospective study of rheumatic
      patients with negative baseline TB screening (tuberculin skin test (TST): <5 mm,
      and negative T-SPOT.TB, QuantiFERON-TB Gold In Tube (QFT-GIT) and chest X-ray)
      treated with anti-TNF agents. All patients underwent re-screening for TB with all
      assays 1 year later. Factors associated with TB test conversion were analysed and
      compared between 'converters' and 'non-converters'. RESULTS: Seventy patients
      (mean age 50.6+/-15.5 years) with rheumatic disease (33 with rheumatoid
      arthritis, 33 with spondyloarthropathies and 4 with other conditions) were
      enrolled. Patients were treated with different anti-TNFs (27 with adalimumab, 14
      etanercept, 16 infliximab, 8 golimumab, 5 certolizumab pegol) for 1 year. Twenty
      patients (29%) displayed conversion of at least one screening assay 12 months
      after anti-TNF therapy: conversion of TST occurred in 9 (13%), T-SPOT.TB in 7
      (10%) and QFT-GIT in 5 (7%). Only one patient had concomitant conversion of more
      than one screening test. Univariate and multivariate analysis revealed that only
      infliximab was associated with a decreased rate of TB screening assay conversion
      (OR 0.048, 95% CI 0.004 to 0.606, p=0.017). No patient (40% received isoniazid
      therapy) developed active TB during follow-up (27+/-12 months). CONCLUSIONS:
      Approximately one third of patients with negative baseline TB screening develop
      conversion of at least one screening test during anti-TNF treatment. These
      findings should be considered when designing re-screening strategies and
      contemplating latent TB therapy.

PMID- 24854355
TI  - Nitrosative modifications of the Ca2+ release complex and actin underlie
      arthritis-induced muscle weakness.
AB  - OBJECTIVE: Skeletal muscle weakness is a prominent clinical feature in patients
      with rheumatoid arthritis (RA), but the underlying mechanism(s) is unknown. Here
      we investigate the mechanisms behind arthritis-induced skeletal muscle weakness
      with special focus on the role of nitrosative stress on intracellular Ca(2+)
      handling and specific force production. METHODS: Nitric oxide synthase (NOS)
      expression, degree of nitrosative stress and composition of the major
      intracellular Ca(2+) release channel (ryanodine receptor 1, RyR1) complex were
      measured in muscle. Changes in cytosolic free Ca(2+) concentration ([Ca(2+)]i)
      and force production were assessed in single-muscle fibres and isolated
      myofibrils using atomic force cantilevers. RESULTS: The total neuronal NOS (nNOS)
      levels were increased in muscles both from collagen-induced arthritis (CIA) mice
      and patients with RA. The nNOS associated with RyR1 was increased and accompanied
      by increased [Ca(2+)]i during contractions of muscles from CIA mice. A marker of
      peroxynitrite-derived nitrosative stress (3-nitrotyrosine, 3-NT) was increased on
      the RyR1 complex and on actin of muscles from CIA mice. Despite increased
      [Ca(2+)]i, individual CIA muscle fibres were weaker than in healthy controls,
      that is, force per cross-sectional area was decreased. Furthermore, force and
      kinetics were impaired in CIA myofibrils, hence actin and myosin showed decreased
      ability to interact, which could be a result of increased 3-NT content on actin.
      CONCLUSIONS: Arthritis-induced muscle weakness is linked to nitrosative
      modifications of the RyR1 protein complex and actin, which are driven by
      increased nNOS associated with RyR1 and progressively increasing Ca(2+)
      activation.

PMID- 24854356
TI  - What is the utility of routine ANA testing in predicting development of
      biological DMARD-induced lupus and vasculitis in patients with rheumatoid
      arthritis? Data from a single-centre cohort.
AB  - OBJECTIVE: To determine whether serial ANA testing predicts biological disease
      modifying antirheumatic drugs (bDMARD)-associated ANA/dsDNA production in
      patients with rheumatoid arthritis (RA). METHODS: Serial autoantibody profiles,
      bDMARD treatment sequences and clinical data were collected from patients
      identified from our database that since 2005 received (i) a first bDMARD (tumour
      necrosis factor inhibitor (TNFi)) and (ii) tocilizumab and/or abatacept. RESULTS:
      Of over 1000 patients, 454 RA patients received a first TNFi. Infliximab group
      demonstrated higher ANA seroconversion rates (31.2%) compared with etanercept
      (11.8%) and adalimumab (16.1%) (p<0.001). Median (range) treatment duration prior
      to ANA seroconversion was 10.9 (1.3-80.0) months. Positive anti-dsDNA titres of
      IgG class (median (range) of 77 IU/mL (65-109)) were noted in six (7.2%)
      patients, within a median (range) of 2.0 (0.8-4.2) years. Three patients
      developed classifiable lupus. 4 of 74 (5.4%) primary non-responders and 24 of 111
      (21.6%) secondary non-responders developed positive ANA antibodies after TNFi
      initiation (p=0.003). Seven (9.5%) tocilizumab-treated patients changed to
      positive ANA; five (8.6%) abatacept-treated patients changed to positive ANA
      status. CONCLUSIONS: This study demonstrates no utility of serial ANA/dsDNA
      testing that could be used to predict onset of seroconversion and therefore the
      development of lupus/vasculitis. An association however between seroconversion
      and the development of a secondary non-response to bDMARD therapy is suggested.

PMID- 24854357
TI  - Electrochemical detection of p-aminophenol by flexible devices based on multi
      wall carbon nanotubes dispersed in electrochemically modified Nafion.
AB  - A conducting composite prepared by dispersing multi-walled carbon nanotubes
      (MWCNTs) into a host matrix consisting of Nafion, electrochemically doped with
      copper, has been prepared, characterized and used to modify one of the gold
      electrodes of simply designed electrochemical cells having copier grade
      transparency sheets as substrates. Electrical measurements performed in deionized
      water show that the Au/Nafion/Au-MWCNTs-Nafion:Cu cells can be successfully used
      in order to detect the presence of p-aminophenol (PAP) in water, without the need
      for any supporting electrolyte. The intensity of the redox peaks arising when PAP
      is added to deionized water is found to be linearly related to the analyte in the
      range from 0.2 to 1.6 uM, with a detection limit of 90 nM and a sensitivity of 7
      uA.(uM(-1)).cm(-2).

PMID- 24854359
TI  - Nanosized thin SnO2 layers doped with Te and TeO2 as room temperature humidity
      sensors.
AB  - In this paper the humidity sensing properties of layers prepared by a new method
      for obtaining doped tin oxide are studied. Different techniques-SEM, EDS in SEM,
      TEM, SAED, AES and electrical measurements-are used for detailed characterization
      of the thin layers. The as-deposited layers are amorphous with great specific
      area and low density. They are built up of a fine grained matrix, consisting of
      Sn- and Te-oxides, and a nanosized dispersed phase of Te, Sn and/or SnTe. The
      chemical composition of both the matrix and the nanosized particles depends on
      the ratio R(Sn/Te) and the evaporation conditions. It is shown that as-deposited
      layers with R(Sn/Te) ranging from 0.4 to 0.9 exhibit excellent characteristics as
      humidity sensors operating at room temperature-very high sensitivity, good
      selectivity, fast response and short recovery period. Ageing tests have shown
      that the layers possess good long-term stability. Results obtained regarding the
      type of the water adsorption on the layers' surface help better understand the
      relation between preparation conditions, structure, composition and humidity
      sensing properties.

PMID- 24854358
TI  - Unusual multiple production of N-acylhomoserine lactones a by Burkholderia sp.
      strain C10B isolated from dentine caries.
AB  - Bacteria realize the ability to communicate by production of quorum sensing (QS)
      molecules called autoinducers, which regulate the physiological activities in
      their ecological niches. The oral cavity could be a potential area for the
      presence of QS bacteria. In this study, we report the isolation of a QS bacterial
      isolate C10B from dentine caries. Preliminary screening using Chromobacterium
      violaceum CV026 biosensor showed that isolate C10B was able to produce N
      acylhomoserine lactones (AHLs). This bacterium was further identified as a member
      of Burkholderia, an opportunistic pathogen. The isolated Burkholderia sp. was
      confirmed to produce N-hexanoyl-L-homoserine lactone (C6-HSL), N-octanoyl-L
      homoserine lactone (C8-HSL), N-decanoyl-L-homoserine lactone (C10-HSL) and N
      dodecanoyl-L-homoserine lactone (C12-HSL). 

PMID- 24854360
TI  - A ubiquitous and low-cost solution for movement monitoring and accident detection
      based on sensor fusion.
AB  - The low average birth rate in developed countries and the increase in life
      expectancy have lead society to face for the first time an ageing situation. This
      situation associated with the World's economic crisis (which started in 2008)
      forces the need of equating better and more efficient ways of providing more
      quality of life for the elderly. In this context, the solution presented in this
      work proposes to tackle the problem of monitoring the elderly in a way that is
      not restrictive for the life of the monitored, avoiding the need for premature
      nursing home admissions. To this end, the system uses the fusion of sensory data
      provided by a network of wireless sensors placed on the periphery of the user.
      Our approach was also designed with a low-cost deployment in mind, so that the
      target group may be as wide as possible. Regarding the detection of long-term
      problems, the tests conducted showed that the precision of the system in
      identifying and discerning body postures and body movements allows for a valid
      monitorization and rehabilitation of the user. Moreover, concerning the detection
      of accidents, while the proposed solution presented a near 100% precision at
      detecting normal falls, the detection of more complex falls (i.e., hampered
      falls) will require further study. 

PMID- 24854362
TI  - Reliable geographical forwarding in cognitive radio sensor networks using virtual
      clusters.
AB  - The need for implementing reliable data transfer in resource-constrained
      cognitive radio ad hoc networks is still an open issue in the research community.
      Although geographical forwarding schemes are characterized by their low overhead
      and efficiency in reliable data transfer in traditional wireless sensor network,
      this potential is still yet to be utilized for viable routing options in resource
      constrained cognitive radio ad hoc networks in the presence of lossy links. In
      this paper, a novel geographical forwarding technique that does not restrict the
      choice of the next hop to the nodes in the selected route is presented. This is
      achieved by the creation of virtual clusters based on spectrum correlation from
      which the next hop choice is made based on link quality. The design maximizes the
      use of idle listening and receiver contention prioritization for energy
      efficiency, the avoidance of routing hot spots and stability. The validation
      result, which closely follows the simulation result, shows that the developed
      scheme can make more advancement to the sink as against the usual decisions of
      relevant ad hoc on-demand distance vector route select operations, while ensuring
      channel quality. Further simulation results have shown the enhanced reliability,
      lower latency and energy efficiency of the presented scheme. 

PMID- 24854361
TI  - Poly (N-isopropylacrylamide) microgel-based optical devices for sensing and
      biosensing.
AB  - Responsive polymer-based materials have found numerous applications due to their
      ease of synthesis and the variety of stimuli that they can be made responsive to.
      In this review, we highlight the group's efforts utilizing thermoresponsive poly
      (N-isopropylacrylamide) (pNIPAm) microgel-based optical devices for various
      sensing and biosensing applications. 

PMID- 24854364
TI  - Robust curb detection with fusion of 3D-Lidar and camera data.
AB  - Curb detection is an essential component of Autonomous Land Vehicles (ALV),
      especially important for safe driving in urban environments. In this paper, we
      propose a fusion-based curb detection method through exploiting 3D-Lidar and
      camera data. More specifically, we first fuse the sparse 3D-Lidar points and high
      resolution camera images together to recover a dense depth image of the captured
      scene. Based on the recovered dense depth image, we propose a filter-based method
      to estimate the normal direction within the image. Then, by using the multi-scale
      normal patterns based on the curb's geometric property, curb point features
      fitting the patterns are detected in the normal image row by row. After that, we
      construct a Markov Chain to model the consistency of curb points which utilizes
      the continuous property of the curb, and thus the optimal curb path which links
      the curb points together can be efficiently estimated by dynamic programming.
      Finally, we perform post-processing operations to filter the outliers,
      parameterize the curbs and give the confidence scores on the detected curbs.
      Extensive evaluations clearly show that our proposed method can detect curbs with
      strong robustness at real-time speed for both static and dynamic scenes. 

PMID- 24854363
TI  - Measurement of the D/H, 18O/16O, and 17O/16O isotope ratios in water by laser
      absorption spectroscopy at 2.73 MUm.
AB  - A compact isotope ratio laser spectrometry (IRLS) instrument was developed for
      simultaneous measurements of the D/H, 18O/16O and 17O/16O isotope ratios in water
      by laser absorption spectroscopy at 2.73 MUm. Special attention is paid to the
      spectral data processing and implementation of a Kalman adaptive filtering to
      improve the measurement precision. Reduction of up to 3-fold in standard
      deviation in isotope ratio determination was obtained by the use of a Fourier
      filtering to remove undulation structure from spectrum baseline. Application of
      Kalman filtering enables isotope ratio measurement at 1 s time intervals with a
      precision (<10/00) better than that obtained by conventional 30 s averaging,
      while maintaining a fast system response. The implementation of the filter is
      described in detail and its effects on the accuracy and the precision of the
      isotope ratio measurements are investigated. 

PMID- 24854366
TI  - Cationic amphiphilic non-hemolytic polyacrylates with superior antibacterial
      activity.
AB  - Acrylic copolymers with appropriate compositions of counits having cationic
      charge with 2-carbon and 6-carbon spacer arms can show superior antibacterial
      activities with concomitant very low hemolytic effect. These amphiphilic
      copolymers represent one of the most promising synthetic polymer antibacterial
      systems reported. 

PMID- 24854365
TI  - [Disseminated histoplasmosis treated by boluses of fluconazole].
AB  - We report a case in which an HIV-infected man was cured of disseminated
      histoplasmosis (Histoplasma capsulatum var duboisii) after treatment by high-dose
      fluconazole (1,600 mg taken four times daily) for 2 months, combined with active
      antiretroviral therapy. The choice of fluconazole at this dosage was motivated by
      its availability as a generic and thus inexpensive medication, the patient's
      precarious status, and his critical clinical condition. At the end of the second
      month of treatment, the patient chose to stop the fluconazole, which he could no
      longer afford, while continuing the antiretroviral treatment, which was free. The
      clinical and laboratory improvement observed from the first week has continued to
      progress for more than 8 months after fluconazole treatment stopped. This single
      case needs - and deserves - to be confirmed in a series of patients. Nonetheless
      it makes it possible to envision fluconazole as a low-cost and efficacious
      antifungal agent for the treatment of disseminated histoplasmosis in AIDS
      patients in sub-Saharan Africa. 

PMID- 24854367
TI  - IgG4-related orbital inflammation presenting as unilateral pseudotumor.
AB  - IgG4 related systemic disease (IgG4-RSD) has been recognised in the last few
      years. Orbital pseudotumor as a presentation of IgG4-RSD is one of the rare
      complaints encountered in pediatric population. It is an inflammatory condition
      of unknown etiology characterized by tumorous swelling of the organs,
      characteristic histopathologic changes and elevated IgG4: IgG plasma cells ratio.
      The disease is also characterized by involvement of varied organ systems. The
      authors describe a seven-year-old boy with orbital pseudotumor after two years of
      initial onset with waxing and waning course, steroid responsive lesion and biopsy
      suggestive of IgG4-RSD involving the extraocular soft tissue. Treatment with oral
      corticosteroids and Azathioprine produced a significant decline in the
      pseudotumor size. It is important for pediatricians to be aware of this condition
      as appropriate recognition and management is important to prevent long-term
      damage of the tissue involved. This is the first case of IgG4 related orbital
      pseudotumor reported from India. 

PMID- 24854369
TI  - Multiresidue analysis of quinolones in water by ultra-high perfomance liquid
      chromatography with tandem mass spectrometry using a simple and effective sample
      treatment.
AB  - A rapid and simple analytical method has been developed for the determination of
      19 quinolones in environmental water samples using ultra high performance liquid
      chromatography with tandem mass spectrometry. Chromatographic and detection
      conditions have been optimized and the separation was achieved in less than 4
      min. The separation was carried out using a new-generation column filled with
      superficially porous particles, resulting in lower backpressure and better
      resolution than totally porous particle columns. The quinolones were detected by
      electrospray ionization in positive mode using multiple-reaction monitoring mode
      for acquisition. A sample treatment based on liquid-liquid extraction and phase
      separation via salting-out was employed to achieve a fast and simple extraction
      that enables the multiresidue analysis. The method has been validated for an
      environmental well water sample from a mountain area. Very low limits of
      detection (between 10 and 90 ng/L) with relative standard deviations lower than
      16.5% and recoveries higher than 73% were achieved. Moreover, well waters from
      different origins (mountain and coast areas and irrigated land) have been
      evaluated and similar results were obtained. 

PMID- 24854368
TI  - Food marketing to children in India: comparative review of regulatory strategies
      across the world.
AB  - Food marketing directed to children is an issue of concern in the present day
      society. Revolution in food industry, increasing globalization and boom in
      information technology has introduced various types of food products and the way
      they are placed in front of likely consumers. This has resulted in rising trend
      of obesity and switch from communicable to non-communicable diseases, which is
      not cost effective for nation as a whole. Multinational companies have targeted
      children as a naive audience to boost their sales. In-ethical practice of
      misleading claims in the advertisements is instrumental in many cases. Food
      marketing to children has been assumed a public health threat since times of
      yore. World Health Organization has resolutions and recommendations on this
      subject. Member countries, including India are a signatory to this declaration.
      However, much needs to be done to counter these multinational food giants.
      Regulations and policies need to be enforced at national and institutional
      levels. Parents must be educated; schools and social organizations to be made
      proactive on this aspect. 

PMID- 24854370
TI  - Catastrophic primary central nervous system vasculitis.
AB  - Primary central nervous system vasculitis (PCNSV) is an uncommon condition that
      affects the brain and the spinal cord. It is heterogeneous in presenting
      characteristics and outcomes. We report a patient with a catastrophic rapidly
      progressive course refractory to intensive treatment with pulses of
      methylprednisolone and iv cyclophosphamide. The condition rapidly deteriorated
      and the patient died 6 weeks after presentation. Rapidly progressive PCNSV
      represents the worst end of the clinical spectrum of PCNSV. These patients are
      characterised by bilateral, multiple, large cerebral vessel lesions on angiograms
      and multiple bilateral cerebral infarctions. 

PMID- 24854371
TI  - ANCA-positive and ANCA-negative phenotypes of eosinophilic granulomatosis with
      polyangiitis (EGPA): outcome and long-term follow-up of 50 patients from a single
      Polish center.
AB  - OBJECTIVES: The aim of the study was to compare the course of the disease and
      treatment outcomes in ANCA-positive and ANCA-negative eosinophilic granulomatosis
      with polyangiitis (EGPA) patients from one Polish tertiary referral centre.
      METHODS: Retrospective and prospective cohort study carried out on 50 patients
      treated in our department between 1998 and 2012. EGPA diagnosis was based on the
      American College of Rheumatology (ACR) criteria. Treatment protocol was based
      primarily on the predictive Five Factor Score (FFS) scale. Clinical
      characteristics of the patients, general symptoms, organ involvement, treatment
      regimen, and follow-up outcomes were evaluated according to ANCA status. RESULTS:
      Fifteen ANCA-positive patients and 35 ANCA-negative patients were enrolled. At
      the time of diagnosis ANCA-positive patients had a higher incidence of renal
      involvement (53% vs. 7.7%; p<0.001), skin involvement (93.3% vs. 57.1%; p=0.03),
      and peripheral neuropathy in the form of mononeuritis multiplex (60% vs. 25.7%;
      p=0.021). ANCA-negative patients had significantly more frequent cardiac
      manifestations, but only with regard to the entire period of follow-up (68.6% vs.
      33.3%; p=0.021). Patients in both groups were under the same treatment regimens,
      however steroid dose necessary to maintain remission of the disease was
      significantly higher in the group of ANCA-positive patients (9+/-2.5 vs. 7.4+/
      1.9 mg/day of methylprednisolone; p=0.023). The presence of ANCA did not affect
      the frequency of relapses. CONCLUSIONS: Our results confirm the differences in
      clinical disease presentation based on ANCA status and indicate that ANCA
      positive patients should be treated more aggressively.

PMID- 24854372
TI  - Practice patterns of ANCA-associated vasculitis: exploring differences among
      subspecialties at a single academic medical centre.
AB  - OBJECTIVES: Clinical trial data help guide physician treatment choices for ANCA
      associated vasculitis (AAV), but when data are lacking, treatment choices are
      largely driven by physician preference. Our aim was to examine AAV treatment
      preferences to determine if patient gender and age, and physician subspecialty
      affect treatment choices. METHODS: Rheumatologists, nephrologists and
      pulmonologists from an academic medical centre participated in a web-based
      survey. Three scenarios (remission induction in severe disease; remission
      maintenance in severe disease; remission induction in limited disease) were
      presented for 4 patient profiles (28- and 68-year-old female/male). Physician
      treatment choices and reasons for these choices were obtained. Differences
      between groups were analysed using Chi-Square and Fisher's exact tests. RESULTS:
      Physicians were significantly more likely to choose rituximab for young females
      for remission induction in severe AAV, with toxicity being the main reason for
      this choice. There was a trend toward rheumatologists choosing rituximab over
      cyclophosphamide compared with other subspecialties for this scenario. Most
      physicians switched to a less toxic agent for remission maintenance, but there
      was little agreement as to choice of maintenance therapy among subspecialties.
      For remission induction in limited disease, most physicians chose rituximab,
      particularly for young females. CONCLUSIONS: Currently, there are very few data
      for remission maintenance therapy following rituximab in severe disease, as well
      as the use of rituximab in limited disease. Choices for treatment of AAV differ
      among subspecialties, are affected by patient gender and age, and tend to be
      largely driven by physician preference when data are limited or lacking.

PMID- 24854373
TI  - Reappraisal of the 1990 American College of Rheumatology criteria for the
      classification of cutaneous vasculitis: an analysis based on 766 patients.
AB  - OBJECTIVES: The term cutaneous vasculitis (CV) includes a wide and heterogeneous
      group of entities. The American College of Rheumatology (ACR) established a set
      of criteria to classify vasculitis in 1990. Our aim was to further investigate
      into the applicability of these criteria for the classification of patients with
      primary CV. METHODS: We analysed a large and unselected series of patients with
      CV attended to a university referral centre from January 1976 to December 2011.
      Patients were classified according to the methodology and criteria proposed by
      the ACR1990 core data set. Patients were also classified according to the same
      ACR 1990 database as proposed by Michel et al. in 1992 to differentiate Henoch
      Schonlein purpura (HSP) from hypersensitivity vasculitis (HV). RESULTS: We
      assessed 766 patients (346 women and 420 men) with a mean age of 34 years.
      Patients with cutaneous lesions in the setting of conditions different from
      primary CV were excluded. According to the 1990 ACR criteria, 405 (63.1%) of the
      642 patients with primary CV were classified as having HSP and 230 (35.8%) as HV.
      However, 119 (18.5%) patients fulfilled the ACR 1990 criteria for both entities.
      In addition, 7 (1.1%) did not meet the ACR 1990 criteria for any of them and,
      therefore, they were considered as non-classified vasculitis. When patients with
      primary CV were tested for the Michel et al. criteria, 392 (61.1%) were
      classified as having HSP and 250 (38.9%) as HV. Frequent discordance between the
      ACR 1990 and the Michel et al. criteria was observed. It ranged between 18.4 and
      21.7% for HSP and 32.2 to 38% for HV. CONCLUSIONS: According to our data, the ACR
      1990 criteria are of limited value for the classification of patients with
      primary CV.

PMID- 24854374
TI  - Isolated aortitis versus giant cell arteritis: are they really two sides of the
      same coin?
AB  - OBJECTIVES: The aim of the study was to compare epidemiological data, clinical
      findings and results of investigations in patients with isolated aortitis and
      those with giant cell arteritis (GCA) to establish whether patients with isolated
      aortitis differ from those with GCA. METHODS: We reviewed the medical notes of
      all patients consecutively seen in two Rheumatology centres in the last two
      decades with a suspicion of GCA, searching for cases characterised by abnormal
      [18F] fluorodeoxyglucose (FDG) PET uptake of the aorta. 'Isolated aortitis' was
      defined as increased FDG uptake in the aorta not explained by atherosclerosis in
      the absence of FDG uptake in other large vessels. RESULTS: Comparing the
      epidemiological and clinical data of patients with isolated arteritis with those
      with GCA, we observed many statistical significant differences. First of all, the
      male/female ratio was reversed, with a predominant male involvement in isolated
      arteritis. Moreover, the mean age of patients with isolated arteritis was
      significantly lower than that of GCA patients (62 vs. 78.4 yrs; p<0.0001). None
      of the patients with isolated aortitis presented at any time of the disease
      course the typical symptoms of GCA, while in a low percentage of cases
      constitutional symptoms represented the only clinical features. Beside the aortic
      arch, the sites more frequent involved were the thoracic and abdominal tracts, in
      all cases without an uptake of the aortic branches. CONCLUSIONS: It is not known
      whether our patients with isolated aortitis represent variants of GCA or TA, nor
      is it known how they will evolve, but we can certainly conclude that these
      patients have a different epidemiologic and clinical profile, and do not
      necessarily represent two sides of the same coin.

PMID- 24854376
TI  - Tocilizumab, an effective treatment for relapsing giant cell arteritis.
AB  - OBJECTIVES: Patients with giant cell arteritis (GCA) often respond to
      corticosteroid (CS) therapy; however, the majority of patients relapse when CS
      therapy is tapered or withdrawn. The purpose of this study was to assess the
      efficacy of tocilizumab (TCZ) in patients with relapsing GCA. METHODS: Four
      patients with relapsing GCA received TCZ monthly (4mg/kg or 8mg/kg). Disease
      activity and drug tolerability were evaluated clinically and via laboratory test
      results at the beginning of the study and every 3 months until the publication of
      this study. All four patients were still receiving TCZ monthly at the time of
      manuscript submission. RESULTS: All four patients treated with TCZ achieved
      clinical and laboratory response. No adverse events were detected. CONCLUSIONS:
      In our small case series, TCZ was efficacious and well tolerated in patients with
      relapsing GCA. Proper randomised controlled trials are required to achieve
      confident conclusions regarding the safety and efficacy of TCZ in GCA.

PMID- 24854375
TI  - Cytomegalovirus-related necrotising vasculitis mimicking Henoch-Schonlein
      syndrome.
AB  - Viral vasculitides have been previously reported in the literature, the role of
      infections in their pathogenesis ranging from direct cause to trigger event. Here
      we report the case of a 3-year-old immunocompetent girl who developed a systemic
      vasculitis leading to ileal perforation, mimicking a full blown picture of Henoch
      Schonlein purpura. High dosage steroid treatment was started, with good response.
      The anatomopathological examination of the resected gastrointestinal tract showed
      features of necrotising vasculitis and cytomegalovirus (CMV)-related inclusion
      bodies in the endothelial cells, with direct correlation to vascular damage. The
      causative role of viral infection was revealed by the presence of CMV DNA in
      patient's blood and positive IgG titer against the virus. Steroid therapy was
      then tapered: the patient achieved clinical remission, which still persists after
      a six-months follow-up. Our report suggests that CMV vasculitis is probably more
      frequent than previously thought, even in immunocompetent patients, with a
      protean clinical presentation, mimicking other types of vasculitides. 

PMID- 24854378
TI  - Genetics of ANCA-associated vasculitides: HLA and beyond.
AB  - The pathogenesis of ANCA-associated vasculitis (AAV) is multifactorial and most
      likely involves the interaction of environmental and genetic factors. During the
      past few years, a number of studies have investigated genetic associations with
      AAV; earlier studies explored associations with single nucleotide polymorphisms
      (SNPs) at genes of potential pathogenetic interest ('candidate gene' studies),
      whereas more recent larger studies analysed associations with SNPs covering ~90%
      of the human genome (genome-wide association studies - GWAS). The latter studies
      have significantly advanced our understanding of the genetic aspects of AAV,
      confirming some previously reported findings and uncovering new genetic
      associations. In addition, these studies have also shown that different AAV
      subtypes such as granulomatosis with polyangiitis (Wegener's, GPA) and
      microscopic polyangiitis (MPA) are underpinned by distinct genetic risk factors,
      with GPA being associated with HLA-DP, SERPINA1 (encoding alpha1-antitrypsin),
      PRTN3 (encoding proteinase-3, PR3, the main GPA-related autoantigen) and SEMA6A
      (semaphorin 6A), whereas MPA has been mainly associated with HLA-DQ.
      Interestingly, in the European GWAS, which included both GPA and MPA patients,
      the HLA-DP, SERPINA1, PRTN3 and HLA-DQ SNPs were more significantly associated
      with ANCA-specificities (PR3 vs. myeloperoxidase, MPO) than with the clinical
      syndromes. In addition, the finding of GPA and PR3-positive subsets being
      associated with SNPs of genes encoding PR3 and alpha1-antitrypsin, a protease
      able to inactivate PR3, highlighted the central role of PR3 as an auto-antigen in
      AAV. This paper reviews the main genetic association studies in AAV, with
      particular emphasis on the two GWAS performed so far. 

PMID- 24854377
TI  - Tocilizumab in refractory aortitis: study on 16 patients and literature review.
AB  - OBJECTIVES: Non-infectious aortitis is often refractory to standard
      immunosuppressive therapy. Since IL-6 has been implicated in the pathogenesis of
      aortitis, we assessed the efficacy of the anti-IL6 receptor monoconal antibody
      tocilizumab (TCZ) in a series of patients with refractory non-infectious
      aortitis. METHODS: Review of 16 patients (14 women/2 men) with refractory
      aortitis diagnosed by imaging (CT angiography, MR angiography, and/or PET) that
      were treated with TCZ. RESULTS: The mean age+/-SD was 51.4+/-20.1 years. The
      underlying conditions were: Takayasu arteritis (TakA) (n=7 cases), giant cell
      arteritis (GCA) (n=7), relapsing polychondritis (RP) (n=1), and aortitis
      associated with retroperitoneal fibrosis (n=1). TCZ was the first biologic drug
      used in all patients with GCA and in the patient with aortitis associated with
      retroperitoneal fibrosis but in only 2 of 7 TakA patients. In the remaining cases
      anti-TNF inhibitors were prescribed before TCZ (standard dose was 8 mg/kg/iv/4
      weeks). After a mean+/-SD follow-up of 11.8+/-6.6 months most patients
      experienced clinical improvement, showing reduction of erythrocyte sedimentation
      rate from 43+/-36 mm/1st h to 5+/-4 mm/1st h at last visit. At TCZ onset, 25% of
      patients had fever and 19% polymyalgia rheumatica. These manifestations
      disappeared after 3 months of TCZ therapy. A corticosteroid sparing effect was
      also achieved (from 27.3+/-17.6 mg/day of prednisone at TCZ onset to 4.2+/-3.8
      mg/day at last visit). TCZ had to be discontinued in a patient because of severe
      neutropenia. CONCLUSIONS: TCZ appears to be effective and relatively safe in
      patients with inflammatory aortitis refractory to corticosteroids or to other
      biologic immunosuppressive drugs.

PMID- 24854379
TI  - Systemic vasculitis: an annual critical digest of the most recent literature.
AB  - Herewith we provide our annual digest of the recent literature on systemic
      vasculitis in which we reviewed all the articles published during the last 12
      months on large-, medium- and small-vessel vasculitis, and selected the most
      relevant studies regarding the epidemiology, pathogenesis and management of
      systemic vasculitis. In particular, we focused the attention on giant cell
      arteritis, ANCA-associated vasculitis and cryoglobulinaemia. 

PMID- 24854381
TI  - Antineutrophil cytoplasmic antibodies (ANCA) testing: detection methods and
      clinical application.
AB  - Antineutrophil cytoplasmic antibodies (ANCA) are considered the diagnostic
      biomarker of some necrotising vasculitis such as granulomatosis with polyangiitis
      (GPA), microscopic polyangiitis (MPA) and, to a lesser extent, eosinophilic
      granulomatosis with polyangiitis (EGPA). According to the current
      recommendations, combining indirect immunofluorescence and proteinase 3 (PR3) and
      myeloperoxidase (MPO) antigen specific immunometric assays, in the proper
      clinical setting, assures the best diagnostic specificity. When such conditions
      are satisfied, ANCA are detected in up to 90% of patients with active generalised
      GPA and MPA and in about 40% of patients with EGPA. Cytoplasmic ANCA (C-ANCA)
      with specificity for PR3 are usually found in patients with GPA whereas
      perinuclear ANCA (P-ANCA) in patients with MPA and EGPA. However, ANCA antigen
      specificity is more closely associated with disease phenotype and prognosis than
      clinical diagnosis. The clinical value of serial ANCA testing in monitoring
      disease activity is still debated. Recently, new promising developments in
      methodology and techniques (computer-based image analysis of immunofluorescence
      patterns, novel generation of PR3-/MPO-ANCA immunometric assays and multiplex
      technology) have been proposed but studies comparing the performances of the
      different assays are scarce.

PMID- 24854380
TI  - Large-vessel involvement in giant cell arteritis and polymyalgia rheumatica.
AB  - Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are closely related
      disorders that affect people of middle age and older, and frequently occur
      together. With the widespread use of newer vascular imaging modalities, large
      vessel involvement (LVI) has increasingly been recognised in patients with GCA
      and less often in those with PMR. LVI in GCA can result in complications such as
      aortic aneurysm and dissection, aortic arch syndrome, and limb arteries stenosis,
      while vascular complications in PMR are exceedingly rare. It is still
      controversial which patients should be investigated for LVI, and how LVI should
      be diagnosed, monitored and managed. In this review, we will try to address six
      important issues regarding LVI in GCA and PMR. 

PMID- 24854382
TI  - Rituximab for ANCA-associated vasculitides.
AB  - Among new treatments for ANCA-associated vasculitis, rituximab is the most
      promising. It has already been demonstrated that rituximab is not inferior to
      cyclophosphamide in inducing remission. This drug is therefore an alternative to
      cyclophosphamide for induction treatment. In the long term, it has been shown
      that patients who have received 4 infusions of rituximab to induce remission, not
      followed by a maintenance treatment, have the same relapse rate as patients who
      have been treated with azathioprine for maintenance. This high relapse rate
      supports a maintenance treatment which could also be rituximab. The results
      obtained with rituximab vs. azathioprine are encouraging and could favour
      rituximab use, but long-term results are still needed. Rituximab is safe and side
      effect frequency and severity are comparable to the side effects observed in
      patients treated with cyclophosphamide for induction, and azathioprine or
      methotrexate for maintenance. New studies are needed to evaluate the long-term
      side effects of this biotherapy. 

PMID- 24854383
TI  - Multiple life-threatening relapses in a woman with primary angiitis of the
      central nervous system mimicking brain tumour: a case report.

PMID- 24854384
TI  - Impaired incretin secretion and pancreatic dysfunction with older age and
      diabetes.
AB  - OBJECTIVE: To estimate the impact of aging and diabetes on insulin sensitivity,
      beta-cell function, adipocytokines, and incretin production. METHODS:
      Hyperglycemic clamps, arginine tests and meal tolerance tests were performed in
      50 non-obese subjects to measure insulin sensitivity (IS) and insulin secretion
      as well as plasma levels of glucagon, GLP-1 and GIP. Patients with diabetes and
      healthy control subjects were divided into the following groups: middle-aged type
      2 diabetes (MA-DM), aged Type 2 diabetes (A-DM) and middle-aged or aged subjects
      with normal glucose tolerance (MA-NGT or A-NGT). RESULTS: IS, as determined by
      the homeostasis model assessment, glucose infusion rate, and oral glucose insulin
      sensitivity, was reduced in the aged and DM groups compared with MA-NGT, but it
      was similar in the MA-DM and A-DM groups. Insulinogenic index, first and second
      phase insulin secretion and the disposition indices, but not insulin response to
      arginine, were reduced in the aged and DM groups. Postprandial glucagon
      production was higher in MA-DM compared to MA-NGT. Whereas the GLP-1 production
      was reduced in A-DM, no differences between groups were observed in GIP
      production. CONCLUSIONS: In non-obese subjects, diabetes and aging impair insulin
      sensitivity. Insulin production is reduced by aging, and diabetes exacerbates
      this condition. Aging associated defects superimposed diabetic physiopathology,
      particularly regarding GLP-1 production. On the other hand, the glucose
      independent secretion of insulin was preserved. Knowledge of the complex
      relationship between aging and diabetes could support the development of
      physiopathological and pharmacological based therapies.

PMID- 24854385
TI  - Scavenger receptor class B type I (SR-BI): a versatile receptor with multiple
      functions and actions.
AB  - Scavenger receptor class B type I (SR-BI), is a physiologically relevant HDL
      receptor that mediates selective uptake of lipoprotein (HDL)-derived cholesteryl
      ester (CE) in vitro and in vivo. Mammalian SR-BI is a 509-amino acid, ~82 kDa
      glycoprotein that contains N- and C-terminal cytoplasmic domains, two
      transmembrane domains, as well as a large extracellular domain containing 5-6
      cysteine residues and multiple sites for N-linked glycosylation. The size and
      structural characteristics of SR-BI, however, vary considerably among lower
      vertebrates and insects. Recently, significant progress has been made in
      understanding the molecular mechanisms involved in the
      posttranscriptional/posttranslational regulation of SR-BI in a tissue specific
      manner. The purpose of this review is to summarize the current body of knowledge
      about the events and molecules connected with the
      posttranscriptional/posttranslational regulation of SR-BI and to update the
      molecular and functional characteristics of the insect SR-BI orthologs.

PMID- 24854386
TI  - Biocontrol activity of an alkaline serine protease from Aureobasidium pullulans
      expressed in Pichia pastoris against four postharvest pathogens on apple.
AB  - The yeast-like fungus Aureobasidium pullulans PL5 is a microbial antagonist
      against postharvest pathogens of fruits. The strain is able to produce
      hydrolases, including glucanases, chitinases and proteases. The alkaline serine
      protease gene ALP5 from A. pullulans was cloned, inserted into the vector pPIC9
      to construct pPIC9/ALP5, and then expressed in Pichia pastoris strain KM71. ALP5
      had a molecular mass of 42.9kDa after 5days growth with 1% methanol induction at
      28 degrees C. The recombinant protease expressed in P. pastoris showed its
      highest activity under alkaline conditions (at pH10) and a temperature of 50
      degrees C. The antifungal activity of the recombinant protease was investigated
      against Penicillium expansum, Botrytis cinerea, Monilinia fructicola and
      Alternaria alternata in vitro and on apple. The recombinant protease reduced
      significantly the spore germination and the germ tube length of the tested
      pathogens in PDB medium. The highest level of protease efficacy was observed
      against M. fructicola and B. cinerea, whereas a lower efficacy was observed
      against P. expansum and A. alternata indicating a possible effect of the pathogen
      cell wall composition on the proteolytic activity of the recombinant protease.
      The presence of protease was able to cause the swelling of the hyphae of B.
      cinerea, under an optical microscope. The recombinant protease expressed in P.
      pastoris was more active against the pathogens in vitro than the same enzyme
      expressed in E. coli in previous studies. The efficacy of ALP5 was also evaluated
      against the pathogens in vivo on cv Golden Delicious apples. The protease was
      more efficient in controlling M. fructicola, B. cinerea and P. expansum than A.
      alternata. However, the extent of the activity was dependent on the enzyme
      concentration and the length of fruit storage. This study demonstrated the
      capacity of the alkaline serine protease to keep its enzymatic activity for some
      days in the unfavorable environment of the fruit wounds. The alkaline serine
      protease could be developed as a postharvest treatment with antimicrobial
      activity for fruit undergoing a short storage period. 

PMID- 24854387
TI  - Two-dimensional environmental profiles of growth and fumonisin production by
      Fusarium proliferatum on a wheat-based substrate.
AB  - The effect of water activity (aW; 0.995, 0.99, 0.98, 0.96, 0.94, 0.92, and 0.90),
      temperature (15, 25, and 30 degrees C), incubation time (7, 14, 21 and 28days),
      and their interactions on mycelial growth and fumonisin production on wheat-based
      medium by three Fusarium proliferatum strains isolated from wheat in Argentina
      was evaluated. Maximum growth rates were obtained at the highest aW (0.995) and
      30 degrees C, with growth decreasing as the aW of the medium was reduced. Maximum
      amounts of total fumonisins (FB1, FB2 and FB3) were produced at 0.99 aW and 25
      degrees C after 21 and 28days of incubation for 2 strains, and at 15 degrees C
      and 0.98 aW after 28days of incubation for the third strain. The fumonisin
      concentrations varied considerably depending on the aW and temperature
      interactions assayed. The studied strains had different fumonisin production
      profiles. F. proliferatum ITEM 15661 and ITEM 15664 produced FB1 and FB2 whereas
      F. proliferatum ITEM 15654 was able to produce FB1, FB2 and FB3. Interestingly,
      fumonisin production profiles for each particular strain were related to
      incubation temperatures. Fumonisins were produced from 15 to 30 degrees C and at
      aW values of 0.92 to 0.995 after 21 to 28days of incubation. However at 7 and
      14days of incubation small amounts of fumonisin were produced at aW lower than
      0.94. Two-dimensional profiles of aW by temperature interactions were developed
      from these data to identify areas where conditions indicate a significant risk
      from fumonisin accumulation on wheat. Temperature and aW conditions that resulted
      in fumonisin production are those found during wheat grain development
      (especially milk and dough stages) in the field. This study provides useful base
      line data on conditions representing a high and a low risk for contamination of
      wheat by fumonisins which is becoming of greater concern because this cereal is
      destined mainly for human consumption. 

PMID- 24854388
TI  - Lymph-node ratio classification strongly correlates with cancer survivals of
      patients who underwent r0 resection for gastric cancer with more than 15 nodes
      harvested.
AB  - BACKGROUND: During the last few years, the gastric cancer nodal staging has been
      extensively revised. Lately, a new system emerged in this field with the purpose
      of implementing the prognostic stratification: the lymph-node ratio (LNR). The
      aim of this study was to investigate the prognostic value of the LNR in relation
      to cancer survivors undergoing resection for gastric adenocarcinoma. METHODS: Off
      227 patients undergoing surgical resection for gastric cancer at our Department,
      129 curative gastric resections with more than 15 nodes harvested were selected.
      The LNR was calculated and patients were stratified into 6 subgroups based on the
      ratio values. The subgroups were compared for data analysis. Survivals were
      calculated by the Kaplan-Meier method, and the mean follow-up period was 40
      months. ROC curves were calculated in order to analyze the performance of the LNR
      system. RESULTS: LNR stratification correlated with the stage of the disease,
      with the rate of patients undergoing chemotherapy and patients presenting with a
      relapse of disease at follow-up. Moreover, an increased ratio correlated with a
      worse overall, a disease-free and a disease-specific survival of the patients.
      The ROC curves documented a significant performance of the stratification system
      with the endpoints of disease-free and disease-specific survivals. CONCLUSION:
      LNR stratification correlated with cancer-related survivals in our case series.
      It is a reliable system that might improve current nodal staging and thereby the
      identification of patients with a higher risk of recurrence or cancer-related
      mortality.

PMID- 24854389
TI  - Exploring the early stages of the pH-induced conformational change of influenza
      hemagglutinin.
AB  - Hemagglutinin (HA) mediates the membrane fusion process of influenza virus
      through its pH-induced conformational change. However, it remains challenging to
      study its structure reorganization pathways in atomic details. Here, we first
      applied continuous constant pH molecular dynamics approach to predict the pK(a)
      values of titratable residues in H2 subtype HA. The calculated net-charges in HA1
      globular heads increase from 0e (pH 7.5) to +14e (pH 4.5), indicating that the
      charge repulsion drives the detrimerization of HA globular domains. In HA2 stem
      regions, critical pH sensors, such as Glu103(2), His18(1), and Glu89(1), are
      identified to facilitate the essential structural reorganizations in the fusing
      pathways, including fusion peptide release and interhelical loop transition. To
      probe the contribution of identified pH sensors and unveil the early steps of pH
      induced conformational change, we carried out conventional molecular dynamics
      simulations in explicit water with determined protonation state for each
      titratable residue in different environmental pH conditions. Particularly, energy
      barriers involving previously uncharacterized hydrogen bonds and hydrophobic
      interactions are identified in the fusion peptide release pathway. Nevertheless,
      comprehensive comparisons across HA family members indicate that different HA
      subtypes might employ diverse pH sensor groups along with different fusion
      pathways. Finally, we explored the fusion inhibition mechanism of antibody CR6261
      and small molecular inhibitor TBHQ, and discovered a novel druggable pocket in H2
      and H5 subtypes. Our results provide the underlying mechanism for the pH-driven
      conformational changes and also novel insight for anti-flu drug development.

PMID- 24854390
TI  - Risk factors of pneumothorax after CT-guided coaxial cutting needle lung biopsy
      through aerated versus nonaerated lung.
AB  - PURPOSE: To compare the risk factors of developing a pneumothorax after computed
      tomography-guided lung biopsy in cases in which aerated lung is traversed and in
      cases in which aerated lung is not traversed. MATERIALS AND METHODS: The records
      of 381 patients from July 2005-December 2009 were retrospectively reviewed.
      Multivariable analysis of patient demographic characteristics, lung lesion
      characteristics, and biopsy procedure details was performed with respect to the
      development of pneumothorax. RESULTS: Among 381 patients, 249 biopsies traversed
      aerated lung tissue, and 132 biopsies did not traverse aerated lung tissue.
      Patients in whom aerated lung tissue was traversed had a significantly higher
      rate of pneumothorax. When aerated lung was not traversed, lesion size (<= 2 cm
      vs > 2 cm; P = .025) and pleural-lesion angle (odds ratio = 1.033/degree; P =
      .004) were associated with pneumothorax. When aerated lung was traversed,
      location (middle vs upper; P = .009) and a transfissure approach (yes vs no; P =
      .001) were associated with pneumothorax. CONCLUSIONS: When aerated lung was not
      traversed, lesion size and pleural-lesion angle were associated with
      pneumothorax, and when aerated lung was traversed, location and a transfissure
      approach were associated with pneumothorax.

PMID- 24854391
TI  - Long-term outcome of percutaneous transhepatic balloon angioplasty for portal
      vein stenosis after pediatric living donor liver transplantation: a single
      institute's experience.
AB  - PURPOSE: To evaluate retrospectively the long-term outcomes of percutaneous
      transhepatic balloon angioplasty performed for portal vein stenosis (PVS) after
      pediatric living donor liver transplantation (LDLT). MATERIALS AND METHODS:
      Between October 1997 and December 2013, of 527 pediatric patients (age < 18 y)
      who underwent LDLT in a single institution, 43 patients (19 boys, 24 girls; mean
      age, 4.1 y +/- 4.1) were confirmed to have PVS at direct portography with or
      without manometry and underwent percutaneous interventions, including balloon
      angioplasty with or without stent placement. Technical success, clinical success,
      laboratory findings, manometry findings, patency rates, and major complications
      were evaluated. Follow-up periods after initial balloon angioplasty ranged from 5
      169 months (mean, 119 mo). RESULTS: Technical success was achieved in 65 of 66
      sessions (98.5%) and in 42 of 43 patients (97.7%), and clinical success was
      achieved in 37 of 43 patients (86.0%). Platelet counts improved significantly. Of
      32 patients undergoing manometry, 19 showed significant improvement of pressure
      gradient across the stenosis after percutaneous transhepatic balloon angioplasty.
      At 1, 3, 5, and 10 years after balloon angioplasty, the rates of primary patency
      were 83%, 78%, 76%, and 70%, and the rates of primary-assisted patency were 100%,
      100%, 100%, and 96%. Two major complications subsequent to balloon angioplasty
      were noted: severe asthma attack and portal vein thrombosis. CONCLUSIONS:
      Percutaneous transhepatic balloon angioplasty is a safe and effective treatment
      with long-term patency for PVS after pediatric LDLT.

PMID- 24854393
TI  - Recent identification of an ERK signal gradient governing planarian regeneration.
AB  - Planarians have strong regenerative abilities derived from their adult
      pluripotent stem cell (neoblast) system. However, the molecular mechanisms
      involved in planarian regeneration have long remained a mystery. In particular,
      no anterior-specifying factor(s) could be found, although Wnt family proteins had
      been successfully identified as posterior-specifying factors during planarian
      regeneration (Gurley et al., 2008; Petersen and Reddien, 2008). A recent textbook
      of developmental biology therefore proposes a Wnt antagonist as a putative
      anterior factor (Gilbert, 2013). That is, planarian regeneration was supposed to
      be explained by a single decreasing gradient of the beta-catenin signal from tail
      to head. However, recently we succeeded in demonstrating that in fact the
      extracellular-signal regulated kinases (ERK) form a decreasing gradient from head
      to tail to direct the reorganization of planarian body regionality after
      amputation (Umesono et al., 2013). 

PMID- 24854392
TI  - MR imaging enables measurement of therapeutic nanoparticle uptake in rat N1-S1
      liver tumors after nanoablation.
AB  - PURPOSE: To test the hypothesis that magnetic resonance (MR) imaging can quantify
      intratumoral superparamagnetic iron oxide (SPIO) nanoparticle uptake after
      nanoablation. MATERIALS AND METHODS: SPIO nanoparticles functionalized with
      doxorubicin were synthesized. N1-S1 hepatomas were successfully induced in 17
      Sprague-Dawley rats distributed into three dosage groups. Baseline tumor R2*
      values (the reciprocal of T2*) were determined using 7-tesla (T) MR imaging.
      After intravenous injection of SPIO nanoparticles, reversible electroporation
      (1,300 V/cm, 8 pulses, 100-MUs pulse duration) was applied. Imaging of rats was
      performed to determine tumor R2* values after the procedure, and change in R2*
      (DeltaR2*) was calculated. Inductively coupled plasma mass spectrometry was used
      to determine intratumoral iron (Fe) concentration after the procedure, which
      served as a proxy for SPIO nanoparticle uptake. Mean tumor Fe concentration [Fe]
      and DeltaR2* for each subject were assessed for correlation with linear
      regression, and mean [Fe] for each dosage group was compared with analysis of
      variance. RESULTS: DeltaR2* significantly correlated with tumor SPIO nanoparticle
      uptake after nanoablation (r = 0.50, P = .039). On average, each 0.1-ms(-1)
      increase in R2* corresponded to a 0.1394-mM increase in [Fe]. There was no
      significant difference in mean SPIO nanoparticle uptake among dosage groups (P =
      .57). CONCLUSIONS: Intratumoral SPIO nanoparticle uptake after nanoablation can
      be successfully quantified noninvasively with 7-T MR imaging. Imaging can be used
      as a method to estimate localized drug delivery after nanoablation.

PMID- 24854395
TI  - Galectin-3 and PTEN expression in pancreatic ductal adenocarcinoma, pancreatic
      neuroendocrine neoplasms and gastrointestinal tumors on fine-needle aspiration
      cytology.
AB  - OBJECTIVE: Galectin-3 has been implicated in the carcinogenesis of pancreatic
      ductal adenocarcinoma (PDAC). Its applicability in pancreatic fine-needle
      aspiration (FNA) in separating malignant from benign lesions has never been
      addressed. In addition, a correlation between Galectin-3 and tumor suppressor
      phosphatase and tensin homolog (PTEN) and their potential diagnostic value has
      never been tested. STUDY DESIGN: This study analyzed Galectin-3
      immunohistochemical expression in FNA cell blocks of PDAC, pancreatic
      neuroendocrine neoplasms (PNEN), gastrointestinal stromal tumors (GIST) and non
      tumor pancreatic tissue. In parallel, Galectin-3 and PTEN levels were evaluated
      in a tumor tissue microarray (TMA). RESULTS: Forty-four of 46 PDAC FNA and 32 of
      33 PDAC TMA demonstrated tumor-specific Galectin-3 positivity. In contrast,
      Galectin-3 was not detected in PNEN and GIST. Total loss of PTEN was displayed by
      26 of 33 PDAC, while non-neoplastic tissues all retained PTEN expression.
      CONCLUSION: Galectin-3 could be a valuable marker to help diagnose PDAC and rule
      out PNEN and GIST. In addition, PTEN positivity strongly argues against a
      diagnosis of PDAC. These data also advocate their potential diagnostic roles in
      the work up of challenging cytologic cases requiring ancillary test confirmation.

PMID- 24854394
TI  - A model of British in-hospital mortality among burns patients.
AB  - INTRODUCTION: Mortality among patients treated in hospital for burn is routinely
      examined, but none of the many models in use in the UK was developed using
      nationwide data. The aim of this research was to develop a prediction model using
      national data, representative of the British population. METHODS: Data were
      gathered from the international Burns Injury Database (iBID) and included 66,611
      patients from England and Wales from 2003 to 2011. Core variables were selected
      following systematic review of the literature, expert consultation and then
      supplemented with variables selected through logistic regression. Discrimination
      and calibration of the model were assessed using the area under the receiver
      operating characteristic curve and the Hosmer-Lemeshow chi2 test respectively.
      RESULTS: Overall mortality for the years of the study in England and Wales was
      1.27%. Mortality was predicted by age (and quadratic term) total burn surface
      area, presence of inhalation injury, presence of existing disorders and category
      of injury. The model gave a discrimination area under the curve of 0.97 in both
      internal and external validation. The calibration of the model gave a Hosmer
      Lemeshow chi2 of 11.9 (p=0.3). CONCLUSION: We have reported a strongly predictive
      and theoretically well-founded model of in-patient mortality using nine years of
      data from all burn care services in England and Wales. We recommend this model
      for British burn service development and for international consideration of the
      variables to use in developing similar models with other data sources.

PMID- 24854396
TI  - Nonlethal screening of bat-wing skin with the use of ultraviolet fluorescence to
      detect lesions indicative of white-nose syndrome.
AB  - Definitive diagnosis of the bat disease white-nose syndrome (WNS) requires
      histologic analysis to identify the cutaneous erosions caused by the fungal
      pathogen Pseudogymnoascus [formerly Geomyces] destructans (Pd). Gross visual
      inspection does not distinguish bats with or without WNS, and no nonlethal, on
      site, preliminary screening methods are available for WNS in bats. We demonstrate
      that long-wave ultraviolet (UV) light (wavelength 366-385 nm) elicits a distinct
      orange-yellow fluorescence in bat-wing membranes (skin) that corresponds directly
      with the fungal cupping erosions in histologic sections of skin that are the
      current gold standard for diagnosis of WNS. Between March 2009 and April 2012,
      wing membranes from 168 North American bat carcasses submitted to the US
      Geological Survey National Wildlife Health Center were examined with the use of
      both UV light and histology. Comparison of these techniques showed that 98.8% of
      the bats with foci of orange-yellow wing fluorescence (n=80) were WNS-positive
      based on histologic diagnosis; bat wings that did not fluoresce under UV light
      (n=88) were all histologically negative for WNS lesions. Punch biopsy samples as
      small as 3 mm taken from areas of wing with UV fluorescence were effective for
      identifying lesions diagnostic for WNS by histopathology. In a nonlethal biopsy
      based study of 62 bats sampled (4-mm diameter) in hibernacula of the Czech
      Republic during 2012, 95.5% of fluorescent (n=22) and 100% of nonfluorescent
      (n=40) wing samples were confirmed by histopathology to be WNS positive and
      negative, respectively. This evidence supports use of long-wave UV light as a
      nonlethal and field-applicable method to screen bats for lesions indicative of
      WNS. Further, UV fluorescence can be used to guide targeted, nonlethal biopsy
      sampling for follow-up molecular testing, fungal culture analysis, and histologic
      confirmation of WNS.

PMID- 24854397
TI  - Cytotoxicity of low-shrink composites with new monomer technology on bovine
      dental pulp-derived cells.
AB  - OBJECTIVES: The aim of this study was to evaluate the cytotoxicity of four low
      shrink composites with new monomer technology on the bovine dental pulp-derived
      cells (bDPCs). MATERIALS AND METHODS: Ten samples were prepared for each group
      composites, and the samples were immersed in 7 mL of culture medium for 72 h at
      37 degrees C to extract residual monomer or cytotoxic substances. The culture
      medium containing the material extracts was sterile filtered for use on the cell
      cultures. Materials were incubated in medium with serum for 72 h. bDPCs were
      maintained in a medium with serum. A real-time cell analyzer was used to evaluate
      cell survival. After seeding 200 mL of the cell suspensions into the wells
      (10,000 cells/well) of the E-plate 96, bDPCs were treated with bioactive
      components released by the composite materials (1:1 and 1:2 dilutions) and
      monitored every 15 min for 50 h. RESULTS: According to analysis of variance,
      there were significant differences between the cell indexes of the control and GC
      kalore (p < 0.05) and Bisco Reflexions (p < 0.001) groups for the 1:1 dilutions
      at 25 h. When evaluated at 50 h, 1:1 dilutions of GC Kalore (p < 0.01) and Bisco
      Reflexions (p < 0.001) reduced cell survival significantly. CONCLUSIONS: Although
      composites resins are being advanced, their cytotoxic effects have been
      proceeding till this time. However, two of the four materials tested
      significantly reduced cell viability when compared with control. CLINICAL
      RELEVANCE: Research should focus on the cytotoxicity of composites in addition to
      their mechanical properties.

PMID- 24854398
TI  - Age-related variety in electrolyte levels and prevalence of dysnatremias and
      dyskalemias in patients presenting to the emergency department.
AB  - BACKGROUND: It was found that age and female gender are predisposing factors for
      hyponatremia in patients taking thiazides. OBJECTIVE: To investigate whether a
      relationship exists between age and gender and serum sodium and potassium as well
      as the prevalence rates in a large population of patients presenting to the
      emergency department of a university hospital. METHODS: In this retrospective
      analysis we gathered data on age, gender and current diuretic medication of all
      patients admitted to the emergency department of a large university hospital with
      measurement of serum sodium and potassium between January 1, 2009 and December
      31, 2010. Prevalence rates of and risk factors for electrolyte disorders were
      calculated on the basis of these data. RESULTS: A total of 20,667 patients were
      included in the analysis. Serum sodium levels declined significantly with
      increasing age while serum potassium rose, independent of diuretic medication at
      presentation. The prevalence rates of hyponatremia and hyperkalemia increased
      from 2.3% for hyponatremia in patients aged 16-21 years to 16.9% in patients aged
      >80 years and from 0.8% for hyperkalemia to 10.4%. In the regression analysis,
      age >60 years was a predictor for the presence of hyponatremia and hyperkalemia
      as was current use of diuretic medication. Male gender was associated with a
      decreased prevalence of hyponatremia and hypokalemia, while it was a predictor of
      hyperkalemia. CONCLUSIONS: Sodium levels were lower with increasing age,
      independent of diuretic intake, while potassium levels were higher. We found
      dramatically increasing prevalences of hyponatremia and hyperkalemia with
      increasing age, while no such effect could be found for hypernatremia and
      hypokalemia.

PMID- 24854399
TI  - Hand eczema and use of snus (moist snuff) - a population-based study.
AB  - A possible association between use of snus (Swedish moist snuff) and hand eczema
      was studied. 27,466 individuals responded to questions regarding hand eczema,
      tobacco use and other life style factors in a Swedish Public Health Survey in
      2006, response rate 58%. Of these persons, 12.2% reported daily snus use (men
      22.0%, women 4.3%), 15.5% daily smoking (men 14.4%, women 16.5%). Of snus users
      7.5 % reported hand eczema (men 6.5%, women 11.8%), of smokers 11.7% (men 8.6%,
      women 13.6%) and of non-tobacco-users 9.7% (men 7.9%, women 11.0%). In
      multivariate analysis hand eczema was significantly less common in snus users, in
      total prevalence proportion ratio (PPR) =  0.813, in men PPR =  0.820, but
      significantly more common in smoking women, PPR = 1.238. Physical exercise was a
      confounder; gender an effect modifier. No positive association was demonstrated
      between snus use and hand eczema in contrast to the positive association found
      between smoking and hand eczema in women. 

PMID- 24854400
TI  - Confocal fluorescence microscopy studies of a fluorophore-labeled dirhodium
      compound: visualizing metal-metal bonded molecules in lung cancer (A549) cells.
AB  - The new dirhodium compound [Rh2(MU-O2CCH3)2(eta(1)
      O2CCH3)(phenbodipy)(H2O)3][O2CCH3] (1), which incorporates a bodipy fluorescent
      tag, was prepared and studied by confocal fluorescence microscopy in human lung
      adenocarcinoma (A549) cells. It was determined that 1 localizes mainly in
      lysosomes and mitochondria with no apparent nuclear localization in the 1-100 MUM
      range. These results support the conclusion that cellular organelles rather than
      the nucleus can be targeted by modification of the ligands bound to the Rh2(4+)
      core. This is the first study of a fluorophore-labeled metal-metal bonded
      compound, work that opens up new venues for the study of intracellular
      distribution of dinuclear transition metal anticancer complexes. 

PMID- 24854401
TI  - Metabolic activity measured by FDG PET predicts pathological response in locally
      advanced superior sulcus NSCLC.
AB  - OBJECTIVES: Pathological complete response and tumor regression to less than 10%
      vital tumor cells after induction chemoradiotherapy have been shown to be
      prognostically important in non-small cell lung cancer (NSCLC). Predictive
      imaging biomarkers could help treatment decision-making. The purpose of this
      study was to assess whether postinduction changes in tumor FDG uptake could
      predict pathological response and to evaluate the correlation between residual
      vital tumor cells and post-induction FDG uptake. METHODS: NSCLC patients with
      sulcus superior tumor (SST), planned for trimodality therapy, routinely undergo
      FDG PET/CT scans before and after induction chemoradiotherapy in our institute.
      Metabolic end-points based on standardized uptake values (SUV) were calculated,
      including SUV(max) (maximum SUV), SUV(TTL) (tumor-to-liver ratio), SUV(peak) (SUV
      within 1 cc sphere with highest activity), and SUV(PTL) (peak-to-liver ratio).
      Pathology specimens were assessed for residual vital tumor cell percentages and
      scored as no (grade 3), <10% (grade 2b) and >10% vital tumor cells (grade 2a/1).
      RESULTS: 19 and 23 patients were evaluated for (1) metabolic change and (2)
      postinduction PET-pathology correlation, respectively. Changes in all parameters
      were predictive for grade 2b/3 response. DeltaSUV(TTL) and DeltaSUV(PTL) were
      also predictive for grade 3 response. Remaining vital tumor cells correlated with
      post-induction SUV(peak) (R=0.55; P=0.007) and postinduction SUV(PTL) (R=0.59;
      P=0.004). Postinduction SUV(PTL) could predict both grades 3 and 2b/3 response.
      CONCLUSION: In NSCLC patients treated with chemoradiotherapy, changes in
      SUV(max), SUV(TTL), SUV(peak), and SUV(PTL) were predictive for pathological
      response (grade 2b/3 and for SUV(TTL) and SUV(PTL) grade 3 as well).
      Postinduction SUV(PTL) correlated with residual tumor cells.

PMID- 24854402
TI  - Overcoming crizotinib resistance in ALK-rearranged non-small cell lung cancer.

PMID- 24854403
TI  - The clinical significance of cytology versus histology-based diagnosis in small
      cell lung cancer: a retrospective study.
AB  - OBJECTIVES: The aim of this study was to investigate the clinical significance of
      cytology versus histology-based diagnosis among patients diagnosed with small
      cell lung cancer (SCLC). MATERIALS AND METHODS: Retrospective analysis of medical
      records of 443 patients with histologically or cytologically confirmed small cell
      lung carcinoma (SCLC) was performed. All patients received platinum-based
      chemotherapy regimens. Survival data (overall survival) were compared between
      patients with histology or cytology-based diagnosis in the overall study
      population as well as after stratification of patients according to disease stage
      (limited or extensive) at the time of diagnosis. RESULTS: Distribution of
      demographics and clinicopathological characteristics among the two groups
      ("histology" and "cytology") was similar. No statistically significant
      differences in the survival curves between the "histology" and "cytology" groups
      were found in the overall study population (log rank test, p=0.237), as well as
      in the subgroup of patients with limited disease (log rank test, p=0.474). In
      contrast, patients with histology-based diagnosis had a statistically significant
      longer survival as compared to those with cytology-based diagnosis in the
      extensive disease subgroup (log rank test, p=0.031), but this association was not
      retained after adjusting the analysis for demographics and clinical
      characteristics via a Cox regression model (HR=1.18, 95% CI: 0.96-1.44, p=0.110).
      CONCLUSION: The results of our study suggest that the type of diagnostic modality
      employed (histology or cytology-based) for the establishment of a diagnosis of
      SCLC may not have a significant effect on the overall survival of patients.
      Further studies are warranted to further investigate this important, yet rather
      unexplored, issue.

PMID- 24854404
TI  - Exposure-specific lung cancer risks in Chinese chrysotile textile workers and
      mining workers.
AB  - OBJECTIVE: Whether there is a difference in the exposure-response slope for lung
      cancer between mining workers and textile workers exposed to chrysotile has not
      been well documented. This study was carried out to evaluate exposure-specific
      lung cancer risks in Chinese chrysotile textile workers and mining workers.
      SUBJECTS AND METHODS: A chrysotile mining worker cohort and a chrysotile textile
      worker cohort were observed concurrently for 26 years. Information on workers'
      vital status, occupational history and smoking habits were collected, and causes
      and dates of deaths were verified from death registries. Individual cumulative
      fiber exposures were estimated based on periodic dust/fiber measurements from
      different workshops, job title and duration, and categorized into four levels (Q1
      Q4). Standardized mortality ratios (SMRs) for lung cancer were calculated and
      stratified by industry and job title with reference of the national rates. Cox
      proportional hazard models were fit to estimate the exposure-specific lung cancer
      risks upon adjustment for age and smoking, in which an external control cohort
      consisting of industrial workers without asbestos exposure was used as reference
      group for both textile and mining workers. RESULTS: SMRs were almost consistent
      with exposure levels in terms of job titles and workshops. A clear exposure
      response relationship between lung cancer mortality and exposure levels was
      observed in both cohorts. At low exposure levels (Q1 and Q2), textile workers
      displayed higher death risks of lung cancer than mining workers. However,
      similarly considerably high risks were observed at higher exposure levels, with
      hazard ratios of over 8 and 11 at Q3 and Q4, respectively, for both textile and
      mining workers, after both age and smoking were adjusted. CONCLUSION: The
      chrysotile textile workers appeared to have a higher risk of lung cancer than the
      mining workers at a relatively low exposure level, but no difference was observed
      at a high exposure level, where both cohorts displayed a considerably high risk.

PMID- 24854405
TI  - Using 'dead or dependent' as an outcome measure in clinical trials in Parkinson's
      disease.
AB  - BACKGROUND: Simple, robust, sensitive and clinically meaningful outcome measures
      are required for neuroprotective trials in Parkinson's disease (PD). We explored
      the feasibility of a composite binary outcome measure, 'dead or dependent', in
      such trials using data from a prospective follow-up study of an incident cohort
      of PD patients. METHODS: Two hundred incident patients had an annual follow-up,
      including assessment of the Hoehn-Yahr stage (H-Y) and Schwab and England
      Activities of Daily Living Scale (S&E). Annual scores were converted into binary
      variables (H-Y <3 vs H-Y >=3, and S&E >=80% vs S&E <80%). A new outcome of 'dead
      or dependent' was also created, with dependence in activities of daily living
      defined as S&E <80%. Using these data, sample sizes were calculated for a
      hypothetical three-year randomised trial in which the trial outcome was defined
      by a binary clinical variable, all-cause mortality, or PD-related mortality.
      RESULTS: At 3 years, 18.0% of patients were dead and 38.4% were dead or
      dependent. At 80% power, large sample sizes were required if PD-related mortality
      (n=1938 per study arm) or all-cause mortality (n=734) were used as the outcome,
      even for large treatment effects (30% reduction in relative risk). The new
      outcome of 'death or dependency' required the smallest sample sizes of all the
      outcome measures (n=277 for 30% reduction in relative risk, 627 for a 20%
      reduction). CONCLUSIONS: 'Death or dependency' is a feasible and potentially
      useful outcome measure in PD trials of neuroprotective agents, but further work
      is required to validate its use and define dependency.

PMID- 24854406
TI  - Cancer: turning glioblastoma cells vacuous.

PMID- 24854410
TI  - Mitochondrial disease: gene therapy protects heart in Friedreich's ataxia.

PMID- 24854414
TI  - The other randomization - methods for labeling drug kits.
AB  - PURPOSE: Most phases 2 and 3 blinded randomized clinical trials package study
      drug, e.g., active and placebo, into drug kits for distribution to
      investigational sites. Kits are made so that it is not possible to determine the
      type of drug in the kit. This enables investigators to administer drug to
      patients in a manner that blinds investigators and patients. Kits are labeled
      with unique kit IDs that code for the drug type. Kit lists contain the assignment
      of kit IDs to drug. Algorithms for making kit lists, like algorithms for
      randomizing patients, incorporate randomness to ensure investigators and patients
      are blind to the process. This paper reviews three types of kit list: blocked,
      double randomized, and scrambled, and discusses the operational benefits of what
      a pharmaceutical company might obtain using scrambled lists along with an
      overview of the challenges of generating and extending the lists for large
      trials. METHODS: We reviewed the operational characteristics of three types of
      kit list: blocked, double randomized, and scrambled. RESULTS: Blocked kit lists
      were a popular choice until their unblinding and operational deficiencies became
      well known. The many difficulties associated with blocked kit lists are
      unnecessary and can be avoided by using a double randomized kit list or a
      scrambled kit list. Compared to double randomized kit lists, scrambled kit lists
      can be more easily extended due to their advantage of having randomly sized gaps
      between kit IDs. CONCLUSIONS: Among the three types of kit list, scrambled kit
      lists offer the most flexibility. The adoption of scrambled kit lists has in
      practice provided the many operational benefits described in this paper.

PMID- 24854415
TI  - The use of phase 2 interim analysis to expedite drug development decisions.
AB  - PURPOSE: To expedite drug development, we propose a two-step decision-making
      process that utilizes interim efficacy results from a comparative phase 2 trial
      to determine whether to accelerate subsequent phase 3 preparations, and final
      analysis to ultimately determine whether to conduct phase 3 testing. METHODS: The
      operational characteristics of this process were evaluated by modeling simulated
      data of oncology trials and retrospectively analyzing data from historical
      comparative phase 2 trials. Progression-free survival (PFS) was used as the
      primary endpoint; the estimated PFS hazard ratios (HRs) of <=0.60 at interim and
      of <=0.65 at final analysis favoring the experimental arm were defined as
      positive results. The conditional probability of achieving a target PFS HR at
      final analysis, based on observed interim results, was also estimated by imputing
      post-interim data with and without the proportional hazard assumption. RESULTS:
      Simulations of phase 2 trials showed that estimated interim PFS HRs correlated
      with estimated final PFS HRs, with reasonably low false-positive rates for
      supporting phase 3 "go" decisions at interim. Using observed historical data,
      decisions based on interim PFS analyses also matched final phase 3 "go" and "no
      go" decisions with a false-positive rate of 16.7% (2 of 12 trials) and a false
      negative rate of 9.4% (3 of 32 trials). Analytical modeling accurately predicted
      final PFS HRs from observed interim data when accounting for appropriate
      underlying assumptions. CONCLUSIONS: The results support the usefulness of a two
      step decision-making process that utilizes interim phase 2 results to reduce the
      interval between phase 2 completion and phase 3 initiation.

PMID- 24854416
TI  - A new sesquiterpene from the Hainan gorgonian Menella kanisa Grassoff.
AB  - Chemical investigation of the gorgonian Menella kanisa Grassoff collected from
      the South China Sea led to the isolation of a new sesquiterpene, menecubebane A
      (1), together with three known compounds, 8-methoxy-trans-calamenene (2), 8,9
      dihydro-linderazulene (3) and (3beta)-oleanan-3-ol (4). The structure of 1 was
      determined by detailed analysis of the spectroscopic data especially the NOESY
      spectrum. All the compounds were evaluated for their cytotoxic, brine shrimp
      lethal and antifouling activities.

PMID- 24854407
TI  - HDL-targeted therapies: progress, failures and future.
AB  - Since the discovery in the 1970s that plasma levels of high-density lipoprotein
      cholesterol (HDL-C) are inversely associated with cardiovascular outcome, it has
      been postulated that HDL is anti-atherogenic and that increasing HDL-C levels is
      a promising therapeutic strategy. However, the recent failure of three orally
      active, HDL-C-raising agents has introduced considerable controversy, prompting
      the question of whether increasing the cholesterol cargo of HDL in a non
      selective manner is an effective pharmacological approach for the translation of
      its atheroprotective and vasculoprotective activities. The interrelationships
      between HDL-C concentration, HDL particle number and levels of diverse HDL
      particle subpopulations of defined composition are complex, as are their
      relationships with reverse cholesterol transport and other anti-atherogenic
      functions. Such complexity highlights the incompleteness of our understanding of
      the biology of HDL particles. This article examines the HDL hypothesis in
      molecular and mechanistic terms, focusing on features that have been addressed,
      those that remain to be tested, and potential new targets for future
      pharmacological interventions. 

PMID- 24854413
TI  - Targeting inflammation in the treatment of type 2 diabetes: time to start.
AB  - The role of inflammation in the pathogenesis of type 2 diabetes and associated
      complications is now well established. Several conditions that are driven by
      inflammatory processes are also associated with diabetes, including rheumatoid
      arthritis, gout, psoriasis and Crohn's disease, and various anti-inflammatory
      drugs have been approved or are in late stages of development for the treatment
      of these conditions. This review discusses the rationale for the use of some of
      these anti-inflammatory treatments in patients with diabetes and what we could
      expect from their use. Future immunomodulatory treatments may not target a
      specific disease, but could instead act on a dysfunctional pathway that causes
      several conditions associated with the metabolic syndrome.

PMID- 24854417
TI  - Limited survival in dialysis patients undergoing intact abdominal aortic aneurysm
      repair.
AB  - OBJECTIVE: Elective abdominal aortic aneurysm (AAA) repair in suitable candidates
      is a standard modality. The outcomes of AAA repair in patients with end-stage
      renal disease on dialysis are not well characterized, and there is questionable
      survival advantage in such patients with limited life expectancy. We sought to
      describe outcomes after AAA repair in U.S. dialysis patients. METHODS: The United
      States Renal Data System was used to collect data on intact asymptomatic AAA
      repair procedures in dialysis patients in the United States between 2005 and
      2008. Endovascular AAA repair (EVAR) and open aortic repair (OAR) were identified
      by Current Procedural Terminology codes. Primary outcomes were perioperative (30
      day) mortality and long-term survival. Predictors of mortality were identified by
      multivariate regression models. RESULTS: A total of 1557 patients were identified
      who had undergone elective AAA repair: 261 OAR and 1296 EVAR. The 30-day
      mortality was 11.3% (EVAR, 10.3%; OAR, 16.1%; P = .010), with increased age
      associated with increased mortality (odds ratio, 1.04; 95% confidence interval
      [CI], 1.02-1.07; P = .001). Kaplan-Meier survival estimates were 66.5% at 1 year
      (EVAR, 66.2%; OAR, 68%) and 37.4% at 3 years (EVAR, 36.8%; OAR, 40%; P = .33).
      Median survival was 25.3 months after EVAR and 27.4 months after OAR. Women had a
      higher mortality rate at 1 year (38.7%) compared with men (32.0%) (P = .015).
      There was no significant mortality difference at 1 year in comparing type of
      procedure in both men (EVAR, 31.6%; OAR, 34%; P = .55) and women (EVAR, 39.3%;
      OAR, 36%; P = .60). A Cox proportional hazards model demonstrated that male
      gender (hazard ratio [HR], 0.75; 95% CI, 0.62-0.92; P = .005), increased time on
      dialysis (HR for each year on dialysis, 0.79; 95% CI, 0.75-0.83; P < .001),
      kidney transplantation history (HR, 0.62; 95% CI, 0.43-0.88; P = .008), and
      diagnosis of hypertension (HR, 0.60; 95% CI, 0.48-0.75; P < .001) were protective
      against mortality. Increased age (HR, 1.02; 95% CI, 1.01-1.03; P < .001) and
      diabetes diagnosis (HR, 1.39; 95% CI, 1.13-1.71; P = .002) predicted increased
      mortality. CONCLUSIONS: AAA patients on dialysis have high perioperative and 1
      year mortality rates after EVAR or OAR, particularly diabetics, women, and the
      elderly. This raises questions about the indications for intact AAA repair in
      dialysis patients, in whom the size threshold may need to be raised. Dialysis
      patients may be best served by deferring repair of AAA until AAAs reach large
      size or become symptomatic, especially if OAR is required, given the higher
      perioperative mortality compared with EVAR.

PMID- 24854418
TI  - A cross-sectional analysis of candidate biomarkers of biological effect in
      smokers, never-smokers and ex-smokers.
AB  - CONTEXT: Biomarkers of biological effect (BOBE) have been proposed as potential
      tools to assess tobacco product use, toxicity and disease risk. OBJECTIVE: To
      determine if candidate BOBE can distinguish between smokers, never-smokers and
      former smokers. METHODS: Biomarker levels were compared from 143 smokers, 61
      never-smokers and 61 ex-smokers. RESULTS: In total, 27 candidate biomarkers were
      assessed, 14 were significantly different between smokers and never-smokers (p <
      0.01) and of these 14 biomarkers, 12 were able to distinguish between smokers and
      former smokers (p < 0.05), which indicates the potential for reversibility.
      CONCLUSIONS: A total of 12 of 27 BOBE are potentially useful tools for future
      product assessment.

PMID- 24854420
TI  - Feasibility of long-term cerebral and peripheral regional tissue oxygen
      saturation measurements.
AB  - The aim of this study was to analyse the feasibility of long-term measurements of
      cerebral (crSO2) and peripheral (prSO2) regional tissue oxygen saturation on the
      first day of life by determining the amount of artefacts and their influence on
      rSO2. Near infrared spectroscopy (NIRS) measurements were performed fronto
      parietal left (crSO2) and on the right forearm (prSO2). Arterial oxygen
      saturation (SpO2) was measured by pulse oximetry on the right wrist. Three
      criteria (C) were defined to identify artefacts (C1: missing values, C2: rSO2
      jumping >15%, C3: rSO2 >= SpO2). The number of artefacts as a percentage of
      measurement time and mean rSO2 was calculated after the introduction of each
      criterion. Measurements were performed in 40 neonates. The number of artefacts in
      crSO2 measurements was similar after introduction of C1 (7.37 +/- 4.64%) and
      after introduction of all criteria (8.89 +/- 4.59%). The number of artefacts in
      prSO2 measurements after introduction of C1 was 10.83 +/- 4.21%, and after
      introduction of all criteria significantly higher with 17.78 +/- 4.27%. After
      introduction of C1, further criteria did not significantly change rSO2: crSO2
      (78.6 +/- 1.3% versus 78.5 +/- 1.2%) and prSO2 (83.7 +/- 0.9% versus 83.5 +/-
      0.9%). In conclusion, long-term NIRS measurements of crSO2 and prSO2 are
      feasible, since most artefacts are due to missing values and therefore easy to
      recognize. 

PMID- 24854423
TI  - A trinuclear defect-grid iron(II) spin crossover complex with a large hysteresis
      loop that is readily silenced by solvent vapor.
AB  - A new type of [2*2] matrix-like complexes with one vertex devoid of a metal ion
      has been selectively synthesized. The defect-grid triiron(II) complex exhibits a
      sharp and complete spin-crossover (SCO) from the 1HS-2LS to the 2HS-1LS state
      (HS: high spin; LS: low spin) with wide hysteresis near room temperature.
      Although the "structurally soft" H-bonded vertex, elastically coupled to the
      metal ions, accounts for the stabilization of spin states, it also mediates a
      dramatic, yet reversible, response to the uptake of exogenous solvent molecules
      leading to silencing of the SCO. The high sensitivity towards those guest
      molecules, the short response time upon exposure, and the smooth reversibility of
      guest binding are favorable characteristics for future sensing applications of
      such defect grids. 

PMID- 24854421
TI  - Comparison of the clinical characteristics of diabetic and non-diabetic women
      with community-acquired acute pyelonephritis: a multicenter study.
AB  - OBJECTIVES: Purpose of this study was to compare clinical characteristics and
      treatment outcomes in diabetic and non-diabetic women with community-acquired APN
      (CA-APN). METHODS: We prospectively collected and analyzed clinical data of women
      with CA-APN who attended 11 hospitals in South Korea from March 2010 to February
      2012. RESULTS: Of a total of 775 patients, 246 (31.7%) were diabetic and 529
      (68.3%) non-diabetic. Fewer of the diabetic patients had flank pain (27.6% vs.
      37.2% P = 0.009), symptoms of lower urinary tract infection (57.3% vs. 69.6% P =
      0.001) and costovertebral angle tenderness (54.9% vs. 72.2% P < 0.001). However,
      more of them had C-reactive protein >=20 mg/dL (40.7% vs. 27.4% P < 0.001),
      azotemia (29.3% vs. 13.4% P < 0.001) and bacteremia (53.7% vs. 38.2% P < 0.001).
      Final clinical failure rates and deaths did not differ between the two groups:
      6.9% vs. 4.5%, P = 0.169; 2.0% vs. 1.7%, P = 0.747. However, hospitalization was
      longer in the diabetics than the non-diabetics (median 9.0 days vs. 7.0 days, P <
      0.001). In logistic regression, diabetes was independently associated with longer
      hospitalization (OR 1.7, CI 1.1-2.7, P = 0.011), together with nausea/vomiting,
      history of admission within 1 year, bacteremia, azotemia, and dementia, as well
      as extended-spectrum beta-lactamase (ESBL)-positivity and fluoroquinolone
      resistance of uropathogens. CONCLUSIONS: CA-APN patients with diabetes have more
      severe disease manifestations and require longer hospitalization than non
      diabetic patients although their clinical findings are less clear than those of
      non-diabetic patients.

PMID- 24854422
TI  - TNFalpha and IFNgamma but not perforin are critical for CD8 T cell-mediated
      protection against pulmonary Yersinia pestis infection.
AB  - Septic pneumonias resulting from bacterial infections of the lung are a leading
      cause of human death worldwide. Little is known about the capacity of CD8 T cell
      mediated immunity to combat these infections and the types of effector functions
      that may be most effective. Pneumonic plague is an acutely lethal septic
      pneumonia caused by the Gram-negative bacterium Yersinia pestis. We recently
      identified a dominant and protective Y. pestis antigen, YopE69-77, recognized by
      CD8 T cells in C57BL/6 mice. Here, we use gene-deficient mice, Ab-mediated
      depletion, cell transfers, and bone marrow chimeric mice to investigate the
      effector functions of YopE69-77-specific CD8 T cells and their relative
      contributions during pulmonary Y. pestis infection. We demonstrate that YopE69-77
      specific CD8 T cells exhibit perforin-dependent cytotoxicity in vivo; however,
      perforin is dispensable for YopE69-77-mediated protection. In contrast, YopE69-77
      mediated protection is severely impaired when production of TNFalpha and IFNgamma
      by CD8 T cells is simultaneously ablated. Interestingly, TNFalpha is absolutely
      required at the time of challenge infection and can be provided by either T cells
      or non-T cells, whereas IFNgamma provided by T cells prior to challenge appears
      to facilitate the differentiation of optimally protective CD8 T cells. We
      conclude that cytokine production, not cytotoxicity, is essential for CD8 T cell
      mediated control of pulmonary Y. pestis infection and we suggest that assays
      detecting Ag-specific TNFalpha production in addition to antibody titers may be
      useful correlates of vaccine efficacy against plague and other acutely lethal
      septic bacterial pneumonias. 

PMID- 24854426
TI  - Porous graphene nanoarchitectures: an efficient catalyst for low charge
      overpotential, long life, and high capacity lithium-oxygen batteries.
AB  - The electrochemical performance of lithium-oxygen (Li-O2) batteries awaits
      dramatic improvement in the design of porous cathode electrodes with sufficient
      spaces to accommodate the discharge products and discovery of effective cathode
      catalysts to promote both oxygen reduction reactions and oxygen evolution
      reactions. Herein, we report the synthesis of porous graphene with different pore
      size architectures as cathode catalysts for Li-O2 batteries. Porous graphene
      materials exhibited significantly higher discharge capacities than that of
      nonporous graphene. Furthermore, porous graphene with pore diameter around 250 nm
      showed the highest discharge capacity among the porous graphene with the small
      pores (about 60 nm) and large pores (about 400 nm). Moreover, we discovered that
      addition of ruthenium (Ru) nanocrystals to porous graphene promotes the oxygen
      evolution reaction. The Ru nanocrystal-decorated porous graphene exhibited an
      excellent catalytic activity as cathodes in Li-O2 batteries with a high
      reversible capacity of 17,700 mA h g(-1), a low charge/discharge overpotential
      (about 0.355 V), and a long cycle life up to 200 cycles (under the curtaining
      capacity of 1000 mAh g(-1)). The novel porous graphene architecture inspires the
      development of high-performance Li-O2 batteries.

PMID- 24854427
TI  - Two novel metal borates with three-dimensional open-framework layers constructed
      from [M2B8O20(OH)2] (M = Al, Ga) cluster units.
AB  - Two novel metal borates, Ba[MB4O8(OH)].H2O (M = Al/Ga), with a three-dimensional
      open-framework layer have been synthesized under hydro(solvo)thermal conditions,
      in which the Al(3+)/Ga(3+) ions have been successfully introduced into the
      oxoboron cluster backbone and further linked together to form the open-framework
      layer composed of the [M2B8O20(OH)2] cluster units. The half-unit [MB4O11(OH)]
      can be viewed as analogous to the known [B5O9(OH)] cluster. Interestingly, the
      rare M-O-M linkages play a crucial role in forming the open-framework layer. 

PMID- 24854425
TI  - A signature of attractor dynamics in the CA3 region of the hippocampus.
AB  - The notion of attractor networks is the leading hypothesis for how associative
      memories are stored and recalled. A defining anatomical feature of such networks
      is excitatory recurrent connections. These "attract" the firing pattern of the
      network to a stored pattern, even when the external input is incomplete (pattern
      completion). The CA3 region of the hippocampus has been postulated to be such an
      attractor network; however, the experimental evidence has been ambiguous, leading
      to the suggestion that CA3 is not an attractor network. In order to resolve this
      controversy and to better understand how CA3 functions, we simulated CA3 and its
      input structures. In our simulation, we could reproduce critical experimental
      results and establish the criteria for identifying attractor properties. Notably,
      under conditions in which there is continuous input, the output should be
      "attracted" to a stored pattern. However, contrary to previous expectations, as a
      pattern is gradually "morphed" from one stored pattern to another, a sharp
      transition between output patterns is not expected. The observed firing patterns
      of CA3 meet these criteria and can be quantitatively accounted for by our model.
      Notably, as morphing proceeds, the activity pattern in the dentate gyrus changes;
      in contrast, the activity pattern in the downstream CA3 network is attracted to a
      stored pattern and thus undergoes little change. We furthermore show that other
      aspects of the observed firing patterns can be explained by learning that occurs
      during behavioral testing. The CA3 thus displays both the learning and recall
      signatures of an attractor network. These observations, taken together with
      existing anatomical and behavioral evidence, make the strong case that CA3
      constructs associative memories based on attractor dynamics. 

PMID- 24854428
TI  - Family violence exposure and associated risk factors for child PTSD in a Mexican
      sample.
AB  - This study was undertaken in an effort to help illuminate the deleterious effects
      of traumatic stress on children and families in Mexico. Rates of exposure to
      traumatic events, family and community violence, and posttraumatic stress
      disorder (PTSD) were investigated in 87 school-age children and their mothers.
      Binary logistic regression analysis was performed to examine potential family and
      ecological risk factors for the presence of child PTSD. A total of 51 children
      (58.6%) reported an event that met the DSM-IV A criteria, and 36 children (41.4%;
      20 boys and 16 girls) met criteria for full PTSD. Traumatic exposure in this
      sample was considerable, particularly intense, and chronic as a result of
      interpersonal violence in the home and community. Results support the need for
      preventive systemic interventions targeting the individual level, parent-child
      dyadic level, and the larger cultural and community context. 

PMID- 24854429
TI  - Glucocorticoid receptor gene expression in adipose tissue and associated
      metabolic risk in black and white South African women.
AB  - BACKGROUND: Black women have lower visceral adipose tissue (VAT) but are less
      insulin sensitive than white women; the mechanisms responsible are unknown.
      OBJECTIVE: The study aimed to test the hypothesis that variation in subcutaneous
      adipose tissue (SAT) sensitivity to glucocorticoids might underlie these
      differences. METHODS: Body fatness (dual energy X-ray absorptiometry) and
      distribution (computerized tomography), insulin sensitivity (SI, intravenous and
      oral glucose tolerance tests), and expression of 11beta-hydroxysteroid
      dehydrogenase-1 (11HSD1), hexose-6-phosphate dehydrogenase and glucocorticoid
      receptor-alpha (GRalpha), as well as genes involved in adipogenesis and
      inflammation were measured in abdominal deep SAT, superficial SAT and gluteal SAT
      (GLUT) depots of 56 normal-weight or obese black and white premenopausal South
      African (SA) women. We used a combination of univariate and multivariate
      statistics to evaluate ethnic-specific patterns in adipose gene expression and
      related body composition and insulin sensitivity measures. RESULTS: Although
      11HSD1 activity and mRNA did not differ by ethnicity, GRalpha mRNA levels were
      significantly lower in SAT of black compared with white women, particularly in
      the GLUT depot (0.52+/-0.21 vs 0.91+/-0.26 AU, respectively, P<0.01). In black
      women, lower SAT GRalpha mRNA levels were associated with increased inflammatory
      gene transcript levels and abdominal SAT area, and reduced adipogenic gene
      transcript levels, VAT/SAT ratio and SI. Abdominal SAT 11HSD1 activity associated
      with increased VAT area and decreased SI in white, but not in black women.
      CONCLUSIONS: In black SA women, downregulation of GRalpha mRNA levels with
      obesity and reduced insulin sensitivity, possibly via increased SAT inflammation,
      is associated with reduced VAT accumulation.

PMID- 24854419
TI  - Mito-nuclear discord in six congeneric lineages of Holarctic ducks (genus Anas).
AB  - Many species have Holarctic distributions that extend across Europe, Asia and
      North America. Most genetics research on these species has examined only
      mitochondrial (mt) DNA, which has revealed wide variance in divergence between
      Old World (OW) and New World (NW) populations, ranging from shallow, unstructured
      genealogies to deeply divergent lineages. In this study, we sequenced 20 nuclear
      introns to test for concordant patterns of OW-NW differentiation between mtDNA
      and nuclear (nu) DNA for six lineages of Holarctic ducks (genus Anas). Genetic
      differentiation for both marker types varied widely among these lineages
      (idiosyncratic population histories), but mtDNA and nuDNA divergence within
      lineages was not significantly correlated. Moreover, compared with the
      association between mtDNA and nuDNA divergence observed among different species,
      OW-NW nuDNA differentiation was generally lower than mtDNA divergence, at least
      for lineages with deeply divergent mtDNA. Furthermore, coalescent estimates
      indicated significantly higher rates of gene flow for nuDNA than mtDNA for four
      of the six lineages. Thus, Holarctic ducks show prominent mito-nuclear discord
      between OW and NW populations, and we reject differences in sorting rates as the
      sole cause of the within-species discord. Male-mediated intercontinental gene
      flow is likely a leading contributor to this discord, although selection could
      also cause increased mtDNA divergence relative to weak nuDNA differentiation. The
      population genetics of these ducks contribute to growing evidence that mtDNA can
      be an unreliable indicator of stage of speciation and that more holistic
      approaches are needed for species delimitation. 

PMID- 24854431
TI  - Hypoxia induces autophagy of bone marrow-derived mesenchymal stem cells via
      activation of ERK1/2.
AB  - BACKGROUND: Bone marrow-derived mesenchymal stem cells (bmMSCs) are the most
      promising seed cells for cell transplant therapy. Hypoxia is a known stimulus of
      autophagy. Recent studies showed that hypoxia promotes autophagy of human
      placental chorionic plate-derived mesenchymal stem cells (CP-MSCs). However,
      whether hypoxia affects autophagy of bmMSCs has not been examined. The goal of
      this study was to investigate the effect of hypoxia on autophagy of mouse bmMSCs
      and the underlying mechanisms. METHODS: BmMSCs from mouse bone marrow were
      randomly divided into three groups: control (C), hypoxia (H) and hypoxia +
      reoxygenation (H+R) groups. Subsequent autophagic signals were analyzed by
      immunostaining and Western blot assays. RESULTS: The expression of autophagic
      signals LC-3, Atg5 and Beclin-1, as well as the conversion of LC3B-I to LC3B-II
      in bmMSCs were significantly increased in H group as compared with control
      (p<0.05). These autophagic signals were also higher in H+R group than in H group
      (p<0.05). Also, the expression of phospho-ERK1/2 was significantly increased in H
      and H+R groups as compared with control (p<0.05). Notably, application of ERK1/2
      inhibitor U0126 (5MUM) significantly repressed hypoxia-induced expression of LC-3
      and Atg5, as well as conversion of LC3B-I to LC3B-II (p<0.05). CONCLUSION:
      Hypoxia can induce autophagy of bmMSCs, which depends on activation of ERK1/2
      pathway.

PMID- 24854432
TI  - Modeling of charge transport in ion bipolar junction transistors.
AB  - Spatiotemporal control of the complex chemical microenvironment is of great
      importance to many fields within life science. One way to facilitate such control
      is to construct delivery circuits, comprising arrays of dispensing outlets, for
      ions and charged biomolecules based on ionic transistors. This allows for
      addressability of ionic signals, which opens up for spatiotemporally controlled
      delivery in a highly complex manner. One class of ionic transistors, the ion
      bipolar junction transistors (IBJTs), is especially attractive for these
      applications because these transistors are functional at physiological conditions
      and have been employed to modulate the delivery of neurotransmitters to regulate
      signaling in neuronal cells. Further, the first integrated complementary ionic
      circuits were recently developed on the basis of these ionic transistors.
      However, a detailed understanding of the device physics of these transistors is
      still lacking and hampers further development of components and circuits. Here,
      we report on the modeling of IBJTs using Poisson's and Nernst-Planck equations
      and the finite element method. A two-dimensional model of the device is employed
      that successfully reproduces the main characteristics of the measurement data. On
      the basis of the detailed concentration and potential profiles provided by the
      model, the different modes of operation of the transistor are analyzed as well as
      the transitions between the different modes. The model correctly predicts the
      measured threshold voltage, which is explained in terms of membrane potentials.
      All in all, the results provide the basis for a detailed understanding of IBJT
      operation. This new knowledge is employed to discuss potential improvements of
      ion bipolar junction transistors in terms of miniaturization and device
      parameters. 

PMID- 24854430
TI  - Phosphorylation of glycogen synthase kinase-3beta in metabolically abnormal
      obesity affects immune stimulation-induced cytokine production.
AB  - BACKGROUND: Obesity is a severe health problem worldwide, which leads to multiple
      comorbidities including type 2 diabetes mellitus and cardiovascular diseases.
      Inflammation has been found to be an important characteristic of adipose tissue
      in obese subjects. However, obesity is also associated with compromised immune
      responses to infections and the impact of obesity on immune function has not been
      fully understood. SUBJECTS/METHODS: To clarify the role of obesity in the immune
      responses, we investigated the Toll-like receptor (TLR)-induced cytokine
      secretion by leukocytes from obese and lean subjects. We also investigated the
      relationship between insulin-induced intracellular signaling and cytokine
      production using peripheral blood mononuclear cells (PBMCs) and a monocytic cell
      line THP-1. RESULTS: We found decreased TLR-induced interferon-gamma, interleukin
      6 (IL-6) and tumor necrosis factor-alpha secretions and elevated IL-10 secretion
      by leukocytes from obese subjects when compared with lean controls. PBMCs from
      obese subjects showed enhanced basal Akt and glycogen synthase kinase-3beta (GSK
      3beta) phosphorylation, which did not further increase with insulin and
      lipopolysaccharide (LPS) stimulation. We also found that LPS-induced IkappaBalpha
      degradation was inhibited in PBMCs from obese subjects. By using THP-1 cells with
      GSK-3beta knockdown or cells treated with hyperinsulinemic and high-fatty acid
      conditions, we found that LPS-induced nuclear factor kappaB (NF-kappaB)
      activation was inhibited and cyclic adenosine monophosphate response element
      binding protein (CREB) activation was enhanced. CONCLUSIONS: These findings
      indicate that GSK-3beta is important in the regulation of NF-kappaB and CREB
      activation in leukocytes under the metabolic condition of obesity. Our study
      revealed a key mechanism through which metabolic abnormalities compromise
      leukocyte functions in people with obesity.

PMID- 24854433
TI  - Telomerase as a tumor marker in diagnosis of prostatic intraepithelial neoplasia
      and prostate cancer.
AB  - BACKGROUND: Early diagnosis of prostate cancer (CaP) can be addressed by studying
      prostatic intraepithelial neoplasia (PIN) as precancer (high-grade PIN or HGPIN).
      This article attempts to analyze the diagnostic role of telomerase as an early
      marker of carcinogenesis. METHODS: Complex urological patient evaluation and
      assessment of telomerase activity. RESULTS: Out of 92 patients 44% were diagnosed
      with CaP, 49% with low-grade PIN (LGPIN) in association with benign prostatic
      hyperplasia (BPH), and 7% with HGPIN in association with BPH. Active telomerase
      (AT) in prostate biopsy specimens was detected in 98% of patients with CaP, in
      33% of patients with HGPIN, and in 20% of patients with LGPIN. In the event of
      simultaneous detection of AT and PIN in initial prostate biopsy specimens,
      further monitoring for 0.5-4.0 years revealed CaP development in 50-56% of cases.
      Further follow-up of patients with PIN and absent telomerase activity in initial
      biopsy specimens did not demonstrate the development of CaP. The PSA level was
      significantly higher in patients with active telomerase in the prostate tissue
      than in telomerase negative patients. CONCLUSIONS: Telomerase activity in the
      prostate tissue increases the risk of CaP development in patients with PIN.
      Detection of telomerase activity in prostate biopsy specimens from patients with
      PIN enables selection of a group of patients with high risk of CaP development
      and reduction of the number of prostate biopsies performed in other patients.

PMID- 24854434
TI  - The case for assessing cannabidiol in epilepsy.
AB  - Intractable epilepsies have an extraordinary impact on cognitive and behavioral
      function and quality of life, and the treatment of seizures represents a
      challenge and a unique opportunity. Over the past few years, considerable
      attention has focused on cannabidiol (CBD), the major nonpsychotropic compound of
      Cannabis sativa. Basic research studies have provided strong evidence for safety
      and anticonvulsant properties of CBD. However, the lack of pure,
      pharmacologically active compounds and legal restrictions have prevented clinical
      research and confined data on efficacy and safety to anecdotal reports. Pure CBD
      appears to be an ideal candidate among phytocannabinoids as a therapy for
      treatment-resistant epilepsy. A first step in this direction is to systematically
      investigate the safety, pharmacokinetics, and interactions of CBD with other
      antiepileptic drugs and obtain an initial signal regarding efficacy at different
      dosages. These data can then be used to plan double-blinded placebo-controlled
      efficacy trials. A PowerPoint slide summarizing this article is available for
      download in the Supporting Information section here. 

PMID- 24854435
TI  - NMR metabolomics of human blood and urine in disease research.
AB  - This paper reviews the main applications of NMR metabolomics of blood and urine
      in disease research, over the last 5 years. The broad range of disease types
      addressed attests the increasing interest within the academic and medical
      communities to explore the recognised potential of metabolomics to (1) provide
      insight into underlying disease pathogenesis and (2) unveil new metabolic markers
      for disease diagnosis and follow up. Importantly, most recent studies reveal an
      increasing awareness of possible limitations and pitfalls of the metabolomics
      approach, together with efforts for improved study design and statistical
      validation, which are crucial requisites for the sound development of NMR
      metabolomics and its progress into the clinical setting. 

PMID- 24854436
TI  - Transistor application of alkyl-substituted picene.
AB  - Field-effect transistors (FETs) were fabricated with a thin film of 3,10
      ditetradecylpicene, picene-(C14H29)2, formed using either a thermal deposition or
      a deposition from solution (solution process). All FETs showed p-channel normally
      off characteristics. The field-effect mobility, MU, in a picene-(C14H29)2 thin
      film FET with PbZr0.52Ti0.48O3 (PZT) gate dielectric reached ~21 cm2 V(-1) s(-1),
      which is the highest MU value recorded for organic thin-film FETs; the average MU
      value (<MU>) evaluated from twelve FET devices was 14(4) cm2 V(-1) s(-1). The
      <MU> values for picene-(C14H29)2 thin-film FETs with other gate dielectrics such
      as SiO2, Ta2O5, ZrO2 and HfO2 were greater than 5 cm2 V(-1) s(-1), and the lowest
      absolute threshold voltage, |Vth|, (5.2 V) was recorded with a PZT gate
      dielectric; the average |Vth| for PZT gate dielectric is 7(1) V. The solution
      processed picene-(C14H29)2 FET was also fabricated with an SiO2 gate dielectric,
      yielding MU=3.4*10(-2) cm2 V(-1) s(-1). These results verify the effectiveness of
      picene-(C14H29)2 for electronics applications.

PMID- 24854437
TI  - Characterization of choline trimethylamine-lyase expands the chemistry of glycyl
      radical enzymes.
AB  - The recently identified glycyl radical enzyme (GRE) homologue choline
      trimethylamine-lyase (CutC) participates in the anaerobic conversion of choline
      to trimethylamine (TMA), a widely distributed microbial metabolic transformation
      that occurs in the human gut and is linked to disease. The proposed biochemical
      function of CutC, C-N bond cleavage, represents new reactivity for the GRE
      family. Here we describe the in vitro characterization of CutC and its activating
      protein CutD. We have observed CutD-mediated formation of a glycyl radical on
      CutC using EPR spectroscopy and have demonstrated that activated CutC processes
      choline to trimethylamine and acetaldehyde. Surveys of potential alternate CutC
      substrates uncovered a strict specificity for choline. Homology modeling and
      mutagenesis experiments revealed essential CutC active site residues. Overall,
      this work establishes that CutC is a GRE of unique function and a molecular
      marker for anaerobic choline metabolism. 

PMID- 24854438
TI  - Bibliometric network analysis of glaucoma.
AB  - Elevated intraocular pressure is recognized as the principal risk factor for
      development of optic nerve head (ONH) injury. Lamina cribrosa (LC) cells and
      astrocytes are two types of cells in the ONH. We attempted to identify more
      target genes and predict their underlying molecular mechanisms. In this study, we
      performed meta-analysis of the data from two microarray sets containing samples
      from LC cells and astrocytes each. Our analysis indicated that 47 differentially
      expressed genes (DEGs) had been identified, and 24 of them were used to construct
      a bibliometric network with other related genes, including GSTT1 ENO2, CPE, PTN,
      PTGDS, IL6, MMP1, and EGFR. Further, our results predicted these genes might be
      involved in glaucoma development through Toll-like receptor signaling pathway,
      ErbB signaling pathway, and glioma and other cancer-related pathways. Therefore
      our study provides potential target genes and pathways for future therapeutic
      studies of glaucoma. 

PMID- 24854439
TI  - Ginsenoside Rh2 promotes nonamyloidgenic cleavage of amyloid precursor protein
      via a cholesterol-dependent pathway.
AB  - Ginsenoside Rh2 (Rh2) is a ginseng derivative used in Chinese traditional
      medicine. We investigated whether Rh2 can help prevent Alzheimer's disease
      symptoms and examined underlying mechanisms. We injected Rh2 into tg2576
      Alzheimer's disease model mice and looked for behavioral improvement and senile
      plaque reduction in brain slices. We measured amyloid precursor protein (APP)
      metabolism species changes, amyloid beta40 and 42 levels and beta, gamma
      secretase activity in primary hippocampal neurons. By living cell staining, we
      detected surface and endocytosed APP. We also measured cholesterol and lipid
      rafts in primary neurons. Rh2 treatment significantly improved learning and
      memory performance at 14 months of age; it also reduced brain senile plaques at
      this age. Based on in vitro experiments, we found that Rh2 treatment increased
      soluble APPalpha (sAPPalpha) levels, increased CTFalpha/beta ratios, and reduced
      amyloid beta 40 and 42 concentrations. Surface APP levels dramatically increased.
      Based on living cell staining, we found that Rh2 inhibited APP endocytosis. Based
      on lipid removal and reload experiments, we found that Rh2 can modulate APP by
      reducing cholesterol and lipid raft levels. We concluded that Rh2 improves
      learning and memory function in Alzheimer's disease model mice, and that this
      improvement is accomplished by reducing amyloid beta secretion and APP
      endocytosis, which in turn is achieved by reducing cholesterol and lipid raft
      concentrations. 

PMID- 24854440
TI  - Evaluation of powdery mildew-resistance of grape germplasm and rapid amplified
      polymorphic DNA markers associated with the resistant trait in Chinese wild
      Vitis.
AB  - The resistance of wild Vitis germplasm, including Chinese and American wild Vitis
      and Vitis vinifera cultivars, to powdery mildew (Uncinula necator Burr.) was
      evaluated for two consecutive years under natural conditions. Most of the Chinese
      and North American species displayed a resistant phenotype, whereas all of the
      European species were highly susceptible. The Alachua and Conquistador accessions
      of Vitis rotundifolia species, which originated in North America, were immune to
      the disease, while Baihe-35-1, one of the accessions of Vitis pseudoreticulata,
      showed the strongest resistance among all Chinese accessions evaluated. Three
      rapid amplified polymorphic DNA (RAPD) markers, OPW02-1756, OPO11-964, and OPY13
      661, were obtained after screening 520 random primers among various germplasm,
      and these markers were found to be associated with powdery mildew resistance in
      Baihe-35-1 and in some Chinese species, but not in any European species. Analysis
      of F1 and F2 progenies of a cross between resistant Baihe-35-1 and susceptible
      Carignane (V. vinifera) revealed that the three RAPD markers were linked to the
      powdery resistant trait in Baihe-35-1 plants. Potential applications of the
      identified RAPD markers for gene mapping, marker-assisted selection, and breeding
      were investigated in 168 F2 progenies of the same cross. Characterization of the
      resistant phenotype of the selected F2 seedlings for breeding a new disease
      resistant grape cultivar is in progress.

PMID- 24854441
TI  - A Medicago truncatula H+-pyrophosphatase gene, MtVP1, improves sucrose
      accumulation and anthocyanin biosynthesis in potato (Solanum tuberosum L.).
AB  - We recently cloned MtVP1, a type I vacuolar-type H(+)-translocating inorganic
      pyrophosphatase from Medicago truncatula. In the present study, we investigated
      the cellular location and the function of this H(+)-PPase in Arabidopsis and
      potato (Solanum tuberosum L.). An MtVP1::enhanced green fluorescent protein
      fusion was constructed, which localized to the plasma membrane of onion epidermal
      cells. Transgenic Arabidopsis thaliana overexpressing MtVP1 had more robust root
      systems and redder shoots than wild-type (WT) plants under conditions of cold
      stress. Furthermore, overexpression of MtVP1 in potato accelerated the formation
      and growth of vegetative organs. The tuber buds and stem base of transgenic
      potatoes became redder than those of WT plants, but flowering was delayed by
      approximately half a month. Interestingly, anthocyanin biosynthesis was promoted
      in transgenic Arabidopsis seedlings and potato tuber buds. The sucrose
      concentration of transgenic potato tubers and tuber buds was enhanced compared
      with that of WT plants. Furthermore, sucrose concentration in tubers was higher
      than that in tuber buds. Although there was no direct evidence to support
      Fuglsang's hypothetical model regarding the effects of H(+)-PPase on sucrose
      phloem loading, we speculated that sucrose concentration was increased in tuber
      buds owing to the increased concentration in tubers. Therefore, overexpressed
      MtVP1 enhanced sucrose accumulation of source organs, which might enhance sucrose
      transport to sink organs, thus affecting anthocyanin biosynthesis. 

PMID- 24854442
TI  - Phenotypic and molecular characterization of Colletotrichum species associated
      with anthracnose of banana (Musa spp) in Malaysia.
AB  - Anthracnose caused by Colletotrichum species is a common postharvest disease of
      banana fruit. We investigated and identified Colletotrichum species associated
      with anthracnose in several local banana cultivars based on morphological
      characteristics and sequencing of ITS regions and of the beta-tubulin gene.
      Thirty-eight Colletotrichum isolates were encountered in anthracnose lesions of
      five local banana cultivars, 'berangan', 'mas', 'awak', 'rastali', and 'nangka'.
      Based on morphological characteristics, 32 isolates were identified as
      Colletotrichum gloeosporioides and 6 isolates as C. musae. C. gloeosporioides
      isolates were divided into two morphotypes, with differences in colony color,
      shape of the conidia and growth rate. Based on ITS regions and beta-tubulin
      sequences, 35 of the isolates were identified as C. gloeosporioides and only 3
      isolates as C. musae; the percentage of similarity from BLAST ranged from 95-100%
      for ITS regions and 97-100% for beta-tubulin. C. gloeosporioides isolates were
      more prevalent compared to C. musae. This is the first record of C.
      gloeosporioides associated with banana anthracnose in Malaysia. In a phylogenetic
      analysis of the combined dataset of ITS regions and beta-tubulin using a maximum
      likelihood method, C. gloeosporioides and C. musae isolates were clearly
      separated into two groups. We concluded that C. gloeosporioides and C. musae
      isolates are associated with anthracnose in the local banana cultivars and that
      C. gloeosporioides is more prevalent than C. musae. 

PMID- 24854443
TI  - Preset ureter catheter in laparoscopic radical hysterectomy of cervical cancer.
AB  - The aim of this study was to evaluate the clinical efficacy of a temporary
      ureteral catheter in preventing iatrogenic ureteral damage in cervical cancer
      patients undergoing laparoscopic radical hysterectomy. All cases had confirmed
      diagnoses of cervical cancer preoperatively between December 2008 and December
      2012 in our hospital and were in clinical stages IA2 to IIA. In total, 176
      laparoscopic radical hysterectomy and lymphadenectomy procedures were performed.
      The 176 cases were divided into two groups: ureteral catheters were installed
      using cystoscopy before the operation in 86 patients (group A), and ureteral
      catheters were not placed in 90 patients (group B). These cases were
      retrospectively analyzed based on postoperative hospitalization time and
      intraoperative and postoperative complications. A total of 6 cases (3.41%) had
      ureteral injuries, and 4 of the cases (4.65%) of ureteral injuries occurred in
      group A. In two of these cases, urinary leaking appeared at the post-operative
      8th and 9th days and at the 10th and 25th days, respectively. There were 2 cases
      (2.22%) of ureteral injuries in group B: 1 case of intraoperative direct injury
      and the other of urinary leaking, which appeared at post-operative day 21.
      Statistically significant differences between the two groups were observed in
      operating time and the incidence of hemorrhage, hematuria (including microscopic
      hematuria), post-operative urinary tract infection, and pain (P < 0.05). A
      ureteral catheter that is placed preoperatively can help to identify the ureter
      in laparoscopic radical hysterectomy, but does not decrease the incidence of
      ureteral injury. 

PMID- 24854444
TI  - Genetic variability and phylogenetic aspects in species of the genus
      Macrobrachium.
AB  - The genus Macrobrachium includes prawns, which are widely distributed in lakes,
      floodplains, and rivers in tropical and subtropical regions of South America.
      This genus presents nearly 210 known species with great ecological and economic
      importance. However, few studies are related to the biology of these crustaceans.
      In this study, we analyzed the genetic variability and phylogenetic relationship
      between Macrobrachium amazonicum and Macrobrachium jelskii, which are closely
      related species. Additionally, they are syntopics and their taxonomy poses
      problems because it is difficult to differentiate between the species. We used
      the mitochondrial gene sequences COI and 16S rRNA to assess the genetic structure
      of these species in 3 populations that were collected from Tiete hydrographic
      basin (Sao Paulo State, Brazil). The interspecific comparison of samples that
      were collected at the same and different locations showed a low rate of genetic
      variability. This similarity was attributed to the recent introduction of these
      species in the regions that were sampled and the habitat conditions in which they
      inhabit. In addition, these results may be consistent with the hypothesis that
      they are a single species, interspecific hybrids, or metapopulation. The
      dendrogram analyses did not reveal the formation of clusters, confirming the
      disturbances in the genetic structure of the samples that were analyzed in this
      study. These data are pioneers to these crustaceans, and they confirm the
      ecological and evolutionary problems between these Macrobrachium species. 

PMID- 24854445
TI  - Geographical genetics of Pseudoplatystoma punctifer (Castelnau, 1855)
      (Siluriformes, Pimelodidae) in the Amazon Basin.
AB  - Geographical genetics allows the evaluation of evolutionary processes underlying
      genetic variation within and among local populations and forms the basis for
      establishing more effective strategies for biodiversity conservation at the
      population level. In this study, we used explicit spatial analyses to investigate
      molecular genetic variation (estimated using 7 microsatellite markers) of
      Pseudoplatystoma punctifer, by using samples obtained from 15 localities along
      the Madeira River and Solimoes, Amazon Basin. A high genetic diversity was
      observed associated with a relatively low FST (0.057; P < 0.001), but pairwise
      FST values ranged from zero up to 0.21 when some pairs of populations were
      compared. These FST values have a relatively low correlation with geographic
      distances (r = 0.343; P = 0.074 by Mantel test), but a Mantel correlogram
      revealed that close populations (up to 80 km) tended to be more similar than
      expected by chance (r = 0.360; P = 0.015). The correlogram also showed a
      exponential-like decrease of genetic similarity with distance, with a patch-size
      of around 200 km, compatible with isolation-by-distance and analogous processes
      related to local constraints of dispersal and spatially structured levels of gene
      flow. The pattern revealed herein has important implications for establishing
      strategies to maintain genetic diversity in the species, especially considering
      the threats due to human impacts caused by building large dams in this river
      system. 

PMID- 24854446
TI  - Comparison of the sensitivity of strains of Salmonella enterica serovar
      Typhimurium in the detection of mutagenicity induced by nitroarenes.
AB  - The use of strains of Salmonella enterica serovar Typhimurium with different
      metabolic capacities can indicate the class or classes of compounds present in an
      environmental sample and enable the diagnosis of the mutagenic activity of these
      pollutants adsorbed on particulate matter (PM) in the air. In the present study,
      the sensitivity of Salmonella strains TA98NR, TA98/1,8-DNP6, YG1021, and YG1024
      to detect nitro compounds adsorbed on samples of PM 2.5 was compared from three
      sites in Rio de Janeiro city. Samples were collected using a high-volume sampler
      at three sites: one with light traffic and two with heavy traffic. The assays
      were performed in the presence of 10-50 MUg/ plate organic extracts with and
      without exogenous metabolization. The YG1021 and YG1024 strains showed the
      highest rev/m(3) values, confirming their enhanced sensitivity. As YG1024 also
      demonstrated sensitivity to nitro and amino compounds, we suggest its use in
      research into environmental contamination.

PMID- 24854448
TI  - Association of GSTTI and GSTM1 variants with acute myeloid leukemia risk.
AB  - We aimed to investigate the relationships between polymorphisms of the
      glutathione S-transferases (GSTs) GSTM1, GSTTI, and GSTP1 and the risk of
      developing acute myeloid leukemia (AML). A total of 206 AML cases and 231
      controls were collected for our study. The genotyping of GSTs (GSTM1, GSTTI, and
      GSTP1) was based upon the duplex polymerase chain reaction with the confronting
      two-pair primer (PCR-CTPP) method. Individuals carrying null GSTTI and GSTM1
      genotypes had a 1.52- and 1.78-fold increased risk of developing acute leukemia,
      respectively, compared to non-null genotype carriers (P < 0.05). A high risk was
      observed in those carrying a combination of null genotypes of GSTM1 and GSTTI
      with GSTP1-Val allele genotypes when compared with those carrying wild-type
      genotypes, with an odds ratio (95% confidence interval) of 3.62 (1.53-8.82) (P <
      0.05). These findings indicate that genetic variants of GSTTI and GSTM1
      significantly increase the risk of developing AML. Our study offers important
      insights into the molecular etiology of AML. 

PMID- 24854447
TI  - Association analysis of colorectal cancer susceptibility variants with gastric
      cancer in a Chinese Han population.
AB  - Evidence suggests that some genetic variants are risk factors for both colorectal
      cancer (CRC) and gastric cancer (GC). Thus, we selected 12 reported single
      nucleotide polymorphisms (SNPs) from genome-wide association studies of CRC and
      conducted this case-control study to assess the associations between these SNPs
      and the risk for GC in a southern Chinese population. All SNPs were genotyped in
      249 individuals with GC and 292 healthy population-matched subjects using the
      Sequenom MassArray iPLEX System. Association analyses based on the c2 test and
      binary logistic regression were performed to determine the odds ratio (OR) and
      95% confidence interval (95%CI) for each SNP. A stratified analysis by gender was
      also performed. Borderline significant associations were observed for rs4444235
      (P = 0.070) and rs10411210 (P = 0.084), both fitting the overdominant model. The
      rs4444235 CT genotype showed a protective effect (OR = 0.72, 95%CI = 0.50-1.03),
      while the rs10411210 CT genotype was a risk factor (OR = 1.40, 95%CI = 0.96-2.05)
      as compared with the CC+TT genotype. In the female subgroup, the rs6983267 GT
      genotype (compared with TT, OR = 2.31, 95%CI = 1.07-4.99) and the rs10505477 CT
      genotype (compared with TT, OR = 2.36, 95%CI = 1.09-5.11) significantly increased
      the risk for GC. No significant association was detected for the other SNPs.
      These results provide evidence that known genetic variants associated with CRC
      risk may also confer risk for GC. 

PMID- 24854449
TI  - Dynamic changes in TAP1 expression levels in newborn to weaning piglets, and its
      association with Escherichia coli F18 resistance.
AB  - The transporter associated with antigen processing (TAP) transports peptides from
      the cytosol into the endoplasmic reticulum for subsequent loading onto the major
      histocompatibility complex (MHC) class I molecules. This study showed the dynamic
      changes in the TAP1 expression level in newborn to weaning piglets. Tissue
      expression profiles revealed that the TAP1 gene was expressed at low levels in
      all tissues, and the expression levels were relatively higher in the lung,
      spleen, lymph, and thymus; further, no significant difference was observed in the
      expression in each tissue among the 3 unweaned stages (8, 18, and 30 days).
      Nevertheless, the postweaning (35 days) expression levels in tissues, including
      the spleen, lung, lymph, duodenum, and jejunum were significantly higher than
      those in the unweaned stages. Furthermore, gene ontology and pathway analysis
      showed that TAP1 took part in 38 biological functions and 5 pathway processes,
      including ABC transporters and antigen processing and presentation. These
      analyses showed that the TAP1 gene, which was related to MHC I immune regulation,
      had a stable and low expression level in unweaned stages; however, its expression
      increased in the postweaning stages. The high expression level of TAP1 indicated
      that the gene might play an important role in Escherichia coli F18 resistance. 

PMID- 24854450
TI  - Association of genetic polymorphisms of SAA1 (rs12218) with myocardial infarction
      in a Chinese population.
AB  - Previous studies suggested that genetic polymorphisms of serum amyloid A (SAA)
      were associated with carotid atherosclerosis. However, the relationship between
      genetic polymorphisms of SAA and myocardial infarction (MI) remains unclear. In
      the present study, we analyzed a polymorphism (rs12218) in the SAA1 gene in 840
      MI patients and 840 healthy subjects by polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP) method. We found that the rs12218 CC+CT
      genotype was more frequent among MI patients than among healthy controls (61.1%
      vs 41.9%; P < 0.001). Multivariate regression analysis showed that after
      adjustment for gender, age, smoking, drinking, hypertension, and diabetes, the
      difference remained significant (P < 0.001, odds ratio = 3.332, 95% confidence
      interval = 1.781-9.231). Therefore, we concluded that genetic polymorphisms of
      SAA1 may be a genetic marker of MI in the Chinese population. 

PMID- 24854452
TI  - The misuse of the terminology "standard of care" hampers innovations in surgery.

PMID- 24854451
TI  - Tumor location is a strong predictor of tumor progression and survival in T2
      gallbladder cancer: an international multicenter study.
AB  - OBJECTIVE: To determine the prognostic impact of tumor location in gallbladder
      cancer. BACKGROUND: Depth of tumor is a strong predictor of survival after
      curative resection of gallbladder cancer. However, the gallbladder has a unique
      anatomical relationship with the liver, and the clinical significance of tumor
      location remains unclear. METHODS: For 437 patients with gallbladder cancer who
      underwent resection at 4 international institutions, clinicopathologic
      characteristics and their association with survival were analyzed. Tumor location
      was defined as "hepatic side" or "peritoneal side," and the prognostic
      significance of tumor location was evaluated. RESULTS: Among the 252 patients
      with T2 disease, patients with tumors on the hepatic side (T2h, n = 99) had
      higher rates of vascular invasion, neural invasion, and nodal metastasis than
      patients with tumors on the peritoneal side (T2p, n = 153) (51% vs 19%, 33% vs
      8%, and 40% vs 17%, respectively; P < 0.01 for all). After a median follow-up of
      58.9 months, 3-year and 5-year survival rates were 52.1% and 42.6%, respectively,
      for T2h tumors and 73.7% and 64.7%, respectively, for T2p tumors (P = 0.0006). No
      such differences were observed in T1 or T3 tumors. Multivariate analysis
      confirmed the independent association of hepatic-side location with survival in
      T2 tumors (hazard ratio, 2.7; 95% confidence interval, 1.7-4.2; P < 0.001). This
      subclassification of T2 tumors predicted recurrence in the liver (23% vs 3%; P =
      0.003) and distant lymph nodes (16% vs 3%; P = 0.019) even after radical
      resection. CONCLUSIONS: After curative resection of T2 gallbladder cancer, tumor
      location predicts the pattern of recurrence and survival.

PMID- 24854453
TI  - A Conceptual Technique for Laparoscopic Right Hepatectomy Based on Facts and
      Oncologic Principles: The Caudal Approach.
AB  - OBJECTIVE: To evaluate a new conceptual technique of laparoscopic right
      hepatectomy. BACKGROUND: Despite significant improvements in surgical care in the
      last decades, morbidity is still high after major hepatectomy. Blood loss and
      transfusions are known to significantly increase the risk of postoperative
      complications and cancer recurrence after liver resection. A laparoscopic
      approach may improve perioperative outcomes in these cases, but data in
      literature are limited and the surgical technique is not yet standardized.
      METHODS: A new conceptual technique of right hepatectomy was designed using
      evidence-based facts and oncologic rules: laparoscopy with pneumoperitoneum, low
      central venous pressure, intermittent pedicle clamping, anterior approach without
      mobilization, and parenchymal section with ultrasonic dissector. Thirty patients
      were prospectively enrolled between October 2011 and September 2013. Primary
      endpoint was intraoperative blood loss. RESULTS: Eighty percent of patients
      underwent surgery for malignant disease and cirrhosis was present in 11 patients.
      Benign lesions accounted for 13% of indications, whereas living liver donation
      was performed in 2 cases. Median blood loss was 100 mL (50-700) and transfusion
      rate was 7%. Five patients (16.6%) required conversion to laparotomy, including 2
      using hybrid technique. The median operative time was 360 minutes (210-510). R0
      resection rate was 87% (21/24). Postoperative morbidity rate was 23% (7/30) with
      8 complications including 6 Clavien III-IV. No respiratory complication occurred.
      The median hospital stay was 8 days. No patient died. CONCLUSIONS: This study
      showed that several evidence-based facts could be combined to define a new
      conceptual technique of laparoscopic right hepatectomy allowing for low blood
      loss and morbidity.

PMID- 24854454
TI  - Utilization of small pediatric donors including infants for pancreas and kidney
      transplantation: exemplification of the surgical technique and the surveillance.

PMID- 24854455
TI  - Systematic review of the impact of surgical harm on quality of life after general
      and gastrointestinal surgery.
AB  - OBJECTIVE: To assess the impact of surgical harm on quality of life (QoL) in
      general and gastrointestinal surgery. BACKGROUND: Surgical adverse events (SAEs)
      are associated with poor outcome. Although SAEs are likely to affect QoL, this
      has not been demonstrated in surgery. METHODS: Studies in general and
      gastrointestinal surgery measuring postoperative QoL in patients who suffered
      SAEs were identified. The overall impact of SAEs on QoL scores was determined by
      combining results from different studies. Component scores, adjustment for
      confounders, and time trends were evaluated. RESULTS: Data from 57,058 patients
      in 31 studies were analyzed. Most studies assessed the combined effect of
      different SAEs. High-quality studies adjusted for preoperative QoL. When
      different QoL instruments were scaled down to a common 0 to 1 score, the mean
      difference in QoL between SAE and no-SAE patients was 0.140 in esophagectomy,
      0.110 in the Crohn resection, 0.089 in colorectal resection, 0.085 in gastric
      bypass, 0.072 in cholecystectomy, and 0.060 in inguinal hernia repair. Studies
      evaluating ileal pouch formation and antireflux surgery showed conflicting
      results. SAEs did not significantly affect QoL in emergency laparotomy and
      pancreatectomy. The frequency of SAEs was 5% to 48%. Physical QoL was affected
      more than emotional QoL. CONCLUSIONS: Significantly negative effects of SAEs on
      QoL were demonstrated in a range of procedures. Postoperative QoL seems to be a
      surrogate for the severity of impact of SAEs on patients. QoL may be an important
      utility to evaluate the economic and societal impact of SAEs thereby defining the
      threshold for safe practice.

PMID- 24854457
TI  - TEMPO-mediated allylic C-H amination with hydrazones.
AB  - TEMPO-mediated reactions of alkenyl hydrazones afforded azaheterocycles via sp(3)
      C-H allylic amination. The transformation is featured by a sequence of remote
      allylic H-radical shift and allylic homolytic substitution with hydrazone
      radicals. 

PMID- 24854456
TI  - Galactosyl prodrug of palmitoylethanolamide: synthesis, stability, cell
      permeation and cytoprotective activity.
AB  - N-Palmitoylethanolamide (PEA) is emerging as a novel therapeutic agent in the
      treatment of neuropathic pain and neurodegenerative diseases. Unfortunately, PEA
      poorly reaches the central nervous system (CNS), after peripheral administration,
      since it is inactivated through intracellular hydrolysis by lipid amidases. Since
      prodrug approach is one of the most popular methods used to increase cell
      permeability, the aim of this paper consists in the synthesis of a new galactosyl
      prodrug of PEA, the palmitoylethanolamide-succinamyl-D-galactos-6'-yl ester
      (PEAGAL). Biological experiments both in neuroblastoma and in C6 glioma cells,
      together with quantitative analyses performed through a LC-MS-MS technique,
      demonstrate the better efficacy of PEAGAL compared to PEA and its higher cell
      permeation. Our results encourage further experiments in animal models of
      neuropathic pain and of neurological disorders and/or neurodegenerative diseases,
      in order to promote a more effective peripherally administrated derivative of
      PEA.

PMID- 24854475
TI  - Anti-TCR mAb induces peripheral tolerance to alloantigens and delays islet
      allograft rejection in autoimmune diabetic NOD mice.
AB  - BACKGROUND: Clinical application of islet transplantation to treat type 1
      diabetes has been limited by islet allograft destruction by both allogeneic and
      autoimmune diabetogenic T-cell responses. The current study aims at determining
      whether an anti-T-cell receptor (TCR) monoclonal antibody (mAb) has potential as
      a novel and potent induction immunotherapy for islet transplantation. METHODS: We
      have investigated the therapeutic efficacy and mechanisms of action of anti-TCR
      therapy in four different murine models, which comprise either allo- or
      autoimmune responses alone or both together. RESULTS: T-cell response to islet
      allografts was potently abrogated by a brief treatment with an anti-TCRbeta mAb
      (clone H57-597), resulting in long-term survival of BALB/c islet allografts in
      streptozotocin-induced diabetic B6 mice. Moreover, transient anti-TCR treatment
      permanently prevented BALB/c skin allograft rejection on Rag1 B6 recipients that
      were reconstituted with Foxp3 cell-depleted B6 splenocytes, but did not impair
      the reconstituted cells' ability to reject the later transplanted C3H skin
      allografts (transplanted at 120 days after BALB/c skin grafting). Transient anti
      TCR treatment was also able to completely prevent diabetes onset in
      NOD.SCID.gammac mice that were transferred with lymphocytes from diabetic NOD
      mice. Next, transient anti-TCR treatment significantly prolonged the survival of
      transplanted BALB/c islets in overtly diabetic NOD mice, which comprise both
      allogeneic and autoimmune diabetogenic T-cell responses to the transplanted
      islets. CONCLUSIONS: Overall, anti-TCR mAb induced peripheral tolerance to
      specific alloantigens even in the absence of Foxp3-expressing natural regulatory
      T cells. These findings reveal the potential for using TCR-targeting mAbs as
      induction immunotherapy for islet transplantation.

PMID- 24854458
TI  - Effect of niacin on FGF23 concentration in chronic kidney disease.
AB  - BACKGROUND: Elevated serum phosphorus and FGF23 are independent cardiovascular
      risk factors in patients with chronic kidney disease. In a randomized controlled
      trial of patients with dyslipidemia assigned to either extended release niacin
      (ERN) alone, ERN combined with the selective prostaglandin D2 receptor subtype 1
      inhibitor laropiprant (ERN-L) or placebo, niacin lowered serum phosphorus;
      however, it is not known if it lowers FGF23 concentrations. METHODS: This is an
      ancillary study to a multicenter, randomized, double-blind, placebo-controlled
      trial among patients with dyslipidemia and an estimated glomerular filtration
      rate (eGFR) of 30-74 ml/min/1.73 m(2). Participants were randomized to ERN-L (n =
      162), ERN (n = 97), or placebo (n = 68) in a 3:2:1 ratio for 24 weeks. The
      primary outcome was a change in serum FGF23 concentrations, and secondary
      outcomes were changes in other mineral metabolism parameters. RESULTS: Both the
      ERN and ERN-L groups showed significant declines in serum phosphorus, calcium and
      calcium.phosphorus product at 24 weeks compared to placebo. A significant decline
      from baseline (10.9%, p < 0.01) in the serum FGF23 concentration was observed in
      the ERN group compared to placebo, but not in the ERN-L group compared to placebo
      (p = 0.36 and 0.97 for ERN-L and placebo, respectively), despite equivalent
      declines in serum phosphorus. Similarly, the most marked declines in PTH occurred
      in the ERN-only group versus placebo; no change in PTH was observed in the ERN-L
      group. CONCLUSIONS: In this ancillary study of hyperlipidemic patients with an
      eGFR of 30-74 ml/min/1.73 m(2), ERN alone but not in combination with laropiprant
      lowered FGF23 and PTH concentrations. If confirmed, niacin may provide a novel
      strategy to decrease phosphorus, FGF23, and PTH concentrations in patients with
      chronic kidney disease.

PMID- 24854478
TI  - A (Creative) Portrait of the Uncertain Individual: Self-Uncertainty and
      Individualism Enhance Creative Generation.
AB  - Building on findings that self-uncertainty motivates attempts to restore
      certainty about the self, particularly in ways that highlight one's
      distinctiveness from others, we show that self-uncertainty, relative to
      uncertainty in general, increases creative generation among individualists. In
      Studies 1 to 3, high (but not low) individualists performed better on a creative
      generation task after being primed with self-uncertainty as opposed to general
      uncertainty. In Study 4, this effect emerged only among those who were told that
      the task measured creative as opposed to analytical thinking, suggesting that the
      positive effects of self-uncertainty on performance are specific to tasks that
      bolster perceptions of uniqueness. In Study 5, self-uncertain individualists
      experienced a restoration of self-clarity after being induced to think about
      themselves as more (vs. less) creative. Implications for compensatory responses
      to self-uncertainty and factors that influence creativity are discussed.

PMID- 24854476
TI  - In vivo needle-based electromechanical reshaping of pinnae: New Zealand White
      rabbit model.
AB  - IMPORTANCE: Electromechanical reshaping (EMR) is a low-cost, needle-based, and
      simple means to shape cartilage tissue without the use of scalpels, sutures, or
      heat that can potentially be used in an outpatient setting to perform otoplasty.
      OBJECTIVES: To demonstrate that EMR can alter the shape of intact pinnae in an in
      vivo animal model and to show that the amount of shape change and the limited
      cell injury are proportional to the dosimetry. DESIGN, SETTING, AND SPECIMENS: In
      an academic research setting, intact ears of 18 New Zealand white rabbits
      underwent EMR using 6 different dosimetry parameters (4 V for 5 minutes, 4 V for
      4 minutes, 5 V for 3 minutes, 5 V for 4 minutes, 6 V for 2 minutes, and 6 V for 3
      minutes). A custom acrylic jig with 2 rows of platinum needle electrodes was used
      to bend ears at the middle of the pinna and to perform EMR. Treatment was
      repeated twice per pinna, in proximal and distal locations. Control pinnae were
      not subjected to current application when being bent and perforated within the
      jig. Pinnae were splinted for 3 months along the region of the bend using soft
      silicon sheeting and a cotton bolster. MAIN OUTCOMES AND MEASURES: The ears were
      harvested the day after splints were removed and before euthanasia. Photographs
      of ears were obtained, and bend angles were measured. Tissue was sectioned for
      histologic examination and confocal microscopy to assess changes to microscopic
      structure and cellular viability. RESULTS: Treated pinnae were bent more and
      retained shape better than control pinnae. The mean (SD) bend angles in the 7
      dosimetry groups were 55 degrees  (35 degrees ) for the control, 60 degrees  (15
      degrees ) for 4 V for 4 minutes, 118 degrees  (15 degrees ) for 4 V for 5
      minutes, 88 degrees  (26 degrees ) for 5 V for 3 minutes, 80 degrees  (17 degrees
      ) for 5 V for 4 minutes, 117 degrees  (21 degrees ) for 6 V for 2 minutes, and
      125 degrees  (18 degrees ) for 6 V for 3 minutes. Shape change was proportional
      to electrical charge transfer, which increased with voltage and application time.
      Hematoxylin-eosin staining of the pinnae identified localized areas of cell
      injury and fibrosis in the cartilage and in the surrounding soft tissue where the
      needle electrodes were inserted. This circumferential zone of injury (range, 1.5
      2.5 mm) corresponded to dead cells on cell viability assay, and the diameter of
      this region increased with total electrical charge transfer to a maximum of 2.5
      mm at 6 V for 3 minutes. CONCLUSIONS AND RELEVANCE: Electromechanical reshaping
      produced shape change in intact pinnae of rabbits in this expanded in vivo study.
      A short application of 4 to 6 V can achieve adequate reshaping of the pinnae.
      Tissue injury around the electrodes increases with the amount of total current
      transferred into the tissue and is modest in spatial distribution. This study is
      a critical step toward evaluation of EMR in clinical trials. LEVEL OF EVIDENCE:
      NA.

PMID- 24854477
TI  - Are You Insulting Me? Exposure to Alcohol Primes Increases Aggression Following
      Ambiguous Provocation.
AB  - Considerable research has shown that alcohol consumption can increase aggression
      and produce extremes in other social behaviors. Although most theories posit that
      such effects are caused by pharmacological impairment of cognitive processes,
      recent research indicates that exposure to alcohol-related constructs, in the
      absence of consumption, can produce similar effects. Here we tested the
      hypothesis that alcohol priming is most likely to affect aggression in the
      context of ambiguous provocation. Experiment 1 showed that exposure to alcohol
      primes increased aggressive retaliation but only when an initial provocation was
      ambiguous; unambiguous provocation elicited highly aggressive responses
      regardless of prime exposure. Experiment 2 showed that alcohol prime exposure
      effects are relatively short-lived and that perceptions of the provocateur's
      hostility mediated effects of prime exposure on aggression. These findings
      suggest modification and extension of existing models of alcohol-induced
      aggression.

PMID- 24854479
TI  - Honor and the Stigma of Mental Healthcare.
AB  - Most prior research on cultures of honor has focused on interpersonal aggression.
      The present studies examined the novel hypothesis that honor-culture ideology
      enhances the stigmatization of mental health needs and inhibits the use of mental
      health services. Study 1 demonstrated that people who strongly endorsed honor
      related beliefs and values were especially concerned that seeking help for mental
      health needs would indicate personal weakness and would harm their reputations.
      Studies 2 and 3 showed that honor states in the U.S. South and West invested less
      in mental healthcare resources, compared with non-honor states in the North
      (Study 2), and that parents living in honor states were less likely than parents
      in non-honor states to use mental health services on behalf of their children
      (Study 3). Together, these studies reveal an overlooked consequence of honor
      ideology for psychological well-being at the individual, social, and
      institutional levels.

PMID- 24854480
TI  - Goal Difficulty and Openness to Interpersonal Goal Support.
AB  - When people pursue important goals, they are often surrounded by close others who
      could provide help and support for the achievement of these goals. The present
      work investigated whether people are more likely to be open to such interpersonal
      goal support from a romantic partner when they perceive their goals as being easy
      versus difficult. Using a multiple methods approach, three studies revealed that,
      compared with the pursuit of easy goals, when people pursue difficult goals, they
      are less likely to seek out and be open to support from their romantic partner.
      Studies 2 and 3 revealed that the effect of goal difficulty on openness to
      support was partially mediated by loss in self-efficacy. Finally, Study 3
      revealed that lack of openness to support can have detrimental long-term
      consequences for the relationship, as it undermines relationship well-being.

PMID- 24854481
TI  - A prospective case-control study of non-healing wounds of the lower limbs - the
      value of biopsies for ulcerating carcinoma.
AB  - BACKGROUND: In some leg ulcer patients there is cancer that is responsible for
      lack of healing of such a wound. AIM: This study was aimed at prospective
      analysis of histopathology of non-healing wounds (NHWs) in the patient presenting
      with high and low suspicion for ulcerating carcinoma. MATERIAL AND METHODS: Forty
      patients with NHWs were enrolled and had been prospectively divided into two
      groups: 25 patients with high suspicion for ulcerating carcinoma according to
      their medical history and physical examination, and the second group of 15
      patients without suspicion for malignancy (control group). All NHWs were
      photographed and underwent biopsies. RESULTS: In the control group biopsies did
      not reveal cancers. On the contrary, in 10 patients (40%) from high suspicion
      group biopsies revealed cancers: seven basal cell carcinomas (BCCs), one -
      malignant melanoma, one - Bowen's disease and one - squamous cell carcinomas.
      Histopathology of six of seven BCCs suggested that non-healing benign wound might
      have preceded malignancy. We found that leg ulcers which were small (wound area
      less than 3 cm(2) ), longstanding (duration 24 <= weeks), presenting with
      granulation tissue covering >=75% of the wound area, with a dull pink appearance
      of the granulation tissue, or an atypical clinical presentation, can actually be
      an ulcerating carcinoma. Dull pink granulation tissue or an atypical clinical
      presentation of ulceration, as a single clinical finding, suggested an underlying
      malignancy with a statistical significance (71.5% vs. 0%; P = 0.001 and 27.8% vs.
      0%; P = 0.0049 respectively). CONCLUSIONS: Prevalence of malignancy, primarily:
      BCCs in NHWs, may be higher than expected and clinical features suggestive of
      such a nature of ulcer are an indication for diagnostic biopsy.

PMID- 24854482
TI  - Congenital left atrial appendage aneurysm associated with a systemic embolism.
AB  - A 20 year-old woman presented with systemic embolisation. On subsequent
      investigation, she was diagnosed with a congenital left atrial appendage
      aneurysm. Few case reports are reported in the literature. This cardiac
      malformation presents a diagnostic challenge in patients with cardiomegaly. 

PMID- 24854483
TI  - Effect of red light on the development and quality of mammalian embryos.
AB  - PURPOSE: To assess irradiance and total energy dose from different microscopes
      during the in-vitro embryonic developmental cycle in mouse and pig and to
      evaluate its effect on embryonic development and quality in pig. METHOD: Spectral
      scalar irradiance (380-1050 nm) was measured by a fiber-optic microsensor in the
      focal plane of a dissection microscope, an inverted microscope and a time-lapse
      incubation system. Furthermore, the effect of three different red light levels
      was tested in the time-lapse system on mouse zygotes for 5 days, and on porcine
      zona-intact and zona-free parthenogenetically activated (PA) embryos for 6 days.
      RESULTS: The time-lapse system used red light centered at 625 nm and with a lower
      irradiance level as compared to the white light irradiance levels on the
      dissection and inverted microscopes, which included more energetic radiation <550
      nm. Even after 1000 times higher total energy dose of red light exposure in the
      time-lapse system, no significant difference was found neither in blastocyst
      development of mouse zygotes nor in blastocyst rates and total cell number of
      blastocysts of porcine PA embryos. CONCLUSIONS: Our results indicate that red
      light (625 nm, 0.34 W/m(2)) used in the time-lapse incubation system does not
      decrease the development and quality of blastocysts in both mouse zygotes and
      porcine PA embryos (both zona-intact and zona-free).

PMID- 24854487
TI  - One-step reconstruction of large lower eyelid defects: technique and outcomes.

PMID- 24854484
TI  - Triggering final oocyte maturation with gonadotropin-releasing hormone agonist
      (GnRHa) versus human chorionic gonadotropin (hCG) in breast cancer patients
      undergoing fertility preservation: an extended experience.
AB  - PURPOSE: To analyze the cycle outcomes and the incidence of ovarian
      hyperstimulation syndrome (OHSS), when oocyte maturation was triggered by
      gonadotropin-releasing hormone agonist (GnRHa) versus human chorionic
      gonadotropin (hCG) in breast cancer patients undergoing fertility preservation.
      METHODS: One hundred twenty-nine women aged <= 45 years, diagnosed with stage <=
      3 breast cancer, with normal ovarian reserve who desired fertility preservation
      were included in the retrospective cohort study. Ovarian stimulation was achieved
      utilizing letrozole and gonadotropins. Oocyte maturation was triggered with GnRHa
      or hCG. Baseline AMH levels, number of oocytes, maturation and fertilization
      rates, number of embryos, and the incidence of OHSS was recorded. RESULTS: The
      serum AMH levels were similar between GnRHa and hCG groups (2.7 +/- 1.9 vs. 2.1
      +/- 1.8; p = 0.327). There was one case of mild or moderate OHSS in the GnRHa
      group compared to 12 in the hCG group (2.1 % vs. 14.4 %, p = 0.032). The
      maturation and fertilization rates, and the number of cryopreserved embryos were
      significantly higher in the GnRHa group. CONCLUSIONS: GnRHa trigger improved
      cycle outcomes as evidenced by the number of mature oocytes and cryopreserved
      embryos, while significantly reducing the risk of OHSS in breast cancer patients
      undergoing fertility preservation.

PMID- 24854488
TI  - A high-throughput shotgun mutagenesis approach to mapping B-cell antibody
      epitopes.
AB  - Characterizing the binding sites of monoclonal antibodies (mAbs) on protein
      targets, their 'epitopes', can aid in the discovery and development of new
      therapeutics, diagnostics and vaccines. However, the speed of epitope mapping
      techniques has not kept pace with the increasingly large numbers of mAbs being
      isolated. Obtaining detailed epitope maps for functionally relevant antibodies
      can be challenging, particularly for conformational epitopes on structurally
      complex proteins. To enable rapid epitope mapping, we developed a high-throughput
      strategy, shotgun mutagenesis, that enables the identification of both linear and
      conformational epitopes in a fraction of the time required by conventional
      approaches. Shotgun mutagenesis epitope mapping is based on large-scale
      mutagenesis and rapid cellular testing of natively folded proteins. Hundreds of
      mutant plasmids are individually cloned, arrayed in 384-well microplates,
      expressed within human cells, and tested for mAb reactivity. Residues are
      identified as a component of a mAb epitope if their mutation (e.g. to alanine)
      does not support candidate mAb binding but does support that of other
      conformational mAbs or allows full protein function. Shotgun mutagenesis is
      particularly suited for studying structurally complex proteins because targets
      are expressed in their native form directly within human cells. Shotgun
      mutagenesis has been used to delineate hundreds of epitopes on a variety of
      proteins, including G protein-coupled receptor and viral envelope proteins. The
      epitopes mapped on dengue virus prM/E represent one of the largest collections of
      epitope information for any viral protein, and results are being used to design
      better vaccines and drugs. 

PMID- 24854490
TI  - A systematic review and meta-analysis comparing pancreaticoduodenectomy versus
      limited resection for duodenal gastrointestinal stromal tumors.
AB  - PURPOSE: This study was designed to compare the clinical outcomes of patients who
      underwent limited resection (LR) versus pancreaticoduodenectomy (PD) for duodenal
      gastrointestinal stromal tumors (GISTs). METHODS: A systematic review of the
      literature was performed to identify studies analyzing the clinical outcomes of
      LR and PD for duodenal GISTs. RESULTS: Eleven studies were included, of which 7
      that compared 162 patients who underwent LR versus 98 patients who underwent PD
      were suitable for meta-analysis. Patients who underwent PD were more likely to
      have tumors which were large (>= 5 cm) [76.0 vs. 36.6 %, odds ratio (OR) 5.49, 95
      % confidence interval (CI) 1.8-16.76], with high mitotic count >=5/50 high-power
      field (HPF) (33.7 vs. 18.5 %, OR 2.23, 95 % CI 1.22-4.08), classified as high
      risk (60.3 vs. 32.0 %, OR 3.23, 95 % CI 1.65-6.34), and which were located at D2
      (80.5 vs. 28.6 %, OR 10.33, 95 % CI 5.22-20.47) compared with LR. PD was
      associated with a higher postoperative morbidity rate than LR [48.3 vs. 20.7 %,
      relative risk (RR) 2.34, 95 % CI 1.61-3.42]. LR was not associated with an
      increased local recurrence rate, had a better DFS [hazard ratio (HR) 2.07, 95 %
      CI 1.07-4.01], and lower rate of distant metastasis (8.9 vs. 25.8 %, OR 0.28, 95
      % CI 0.13-0.59) compared with PD. CONCLUSIONS: LR should be the procedure of
      choice for duodenal GIST whenever technically feasible, because it is associated
      with good oncologic outcomes and lower morbidity compared with PD. The oncologic
      outcome of GIST is more likely to be dependent on tumor biology rather that the
      type of surgical resection. The use of Imatinib in patients with duodenal GIST
      may potentially allow a proportion of patients who would otherwise require a PD
      to undergo LR instead.

PMID- 24854489
TI  - Silencing of UCHL1 by CpG promoter hyper-methylation is associated with
      metastatic gastroenteropancreatic well-differentiated neuroendocrine (carcinoid)
      tumors.
AB  - BACKGROUND: Well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP
      NETs) are rare tumors with varying metastatic potential. The underlying molecular
      basis for metastasis by GEP-NETs remains undefined. METHODS: Quantitative PCR and
      immunohistochemistry (IHC) staining for ubiquitin carboxyl-terminal esterase L1
      (UCHL1) gene and protein expression was performed on a group of localized and
      metastatic well-differentiated GEP-NET samples acquired from a prospectively
      maintained tissue bank. The ability of extent of UCHL1 IHC staining to
      differentiate localized and metastatic tumors was compared with Ki-67 index.
      RESULTS: Among 46 total samples, UCHL1 expression at both the gene and protein
      level was significantly greater among localized GEP-NETs compared with metastatic
      tumors and metastases (p < 0.001). Hypermethylation of the UCHL1 promoter was
      commonly observed among metastatic primary tumors and metastases (those with the
      lowest UCHL1 expression) but not among localized tumors (p < 0.001). Poor
      staining (<50 %) for UCHL1 was observed in 27 % of localized tumors compared with
      87 % of metastatic tumors (p = 0.001). The presence of <50 % staining for UCHL1
      was 88 % sensitive and 73 % specific for identifying metastatic disease. In
      contrast, there was no association between Ki-67 index and metastatic disease. In
      multivariable analysis, only UCHL1 staining <50 % [odds ratio (OR) 24.5, p =
      0.035] and vascular invasion (OR 38.4, p = 0.03) were independent risk factors
      for metastatic disease at the time of initial surgery. CONCLUSIONS: Loss of UCHL1
      expression by CpG promoter hypermethylation is associated with metastatic GEP
      NETs. Extent of UCHL1 staining should be explored as a potentially clinically
      useful adjunct to Ki-67 index in evaluating GEP-NETs for aggressive features.

PMID- 24854491
TI  - Preoperative prognostic neurologic index for glioblastoma patients receiving
      tumor resection.
AB  - BACKGROUND: Neurologic status is one of the major prognostic factors in
      glioblastoma patients; however, no consensus exists on a clinical index for
      predicting patient outcomes. The purpose of this study was to evaluate the
      correlation between neurologic deficits and clinical outcomes in glioblastoma
      patients, and to develop a prognostic neurologic index for identifying patients
      with poor outcomes. METHODS: Patients receiving tumor resection with
      pathologically confirmed glioblastoma were retrospectively evaluated. The
      patients' preoperative neurologic deficits were categorized, and patients with
      poor overall survival (OS) were identified. Other common prognostic factors,
      including age, performance, imaging findings, and extent of resection, were
      analyzed. RESULTS: We evaluated 162 glioblastoma patients receiving tumor
      resection between February 2000 and December 2011, of whom 54 received adjuvant
      radiotherapy (RT) alone and 84 received concurrent chemo-RT with temozolomide. At
      a median follow-up of 57.6 (range 26.3-88.9) months, 26 patients had survived
      without loss to follow-up. We defined adverse neurologic status by using an index
      of combined increased intracranial pressure (IICP) and non-IICP signs. In
      univariate analysis, the median OS of patients with and without adverse
      neurologic status were 9.6 and 18.7 months, respectively (p < 0.001). In
      multivariate analyses, adverse neurologic status remained significantly
      associated with poor OS (hazard ratio 2.18, 95 % confidence interval 1.54-3.10).
      CONCLUSIONS: Our proposed neurologic index enables significantly identifying
      glioblastoma patients receiving tumor resection with poor outcomes, independent
      of other common prognostic factors. Using the index provides a preoperative
      predictor of prognosis in glioblastoma patients receiving tumor resection.

PMID- 24854492
TI  - Single-institution retrospective comparison of preoperative versus definitive
      chemoradiotherapy for adenocarcinoma of the esophagus.
AB  - PURPOSE: We sought to determine the impact of esophagectomy on survival in
      patients with adenocarcinoma of the esophagus cancer after chemoradiotherapy
      (CRT). METHODS: A database of esophageal cancer was queried for nonmetastatic
      patients with adenocarcinoma treated between 2000 and 2011 with CRT. Overall
      survival (OS) and recurrence-free survival (RFS) curves were calculated according
      to the Kaplan-Meier method and log-rank analysis. Multivariate analysis was
      performed by the Cox proportional hazard model. RESULTS: We identified 154
      patients (60 without surgery; 94 with surgery) who were included in the analysis.
      The only differences between the 2 groups were more advanced disease stage,
      improved performance status, and younger age in the surgery group. Patients
      undergoing surgery had significantly higher survival. Median and 5-year OS for
      surgical patients were 4.1 years and 43.6 %, versus 1.9 years and 35.6 % for
      nonsurgical patients (p = 0.007). Multivariate analysis for OS and RFS revealed
      that factors associated with increased survival were surgical resection, tumor
      length < 5 cm, male gender, and lower stage. Age, tumor location, radiation
      dose/technique, and induction chemotherapy were not prognostic. There was a trend
      toward improved survival on univariate analysis (p = 0.10) and multivariate
      analysis (p = 0.063) for surgical patients compared to nonsurgical patients who
      were healthy enough for surgery before CRT (n = 38), and no difference in OS in
      nonsurgical patients healthy enough for surgery after CRT (n = 22). CONCLUSION:
      Esophagectomy after CRT is associated with improved survival in patients with
      adenocarcinoma after CRT. Trimodal therapy should continue to remain the standard
      of care for esophageal adenocarcinoma.

PMID- 24854493
TI  - The American Society of Peritoneal Surface Malignancies (ASPSM) Multiinstitution
      Evaluation of the Peritoneal Surface Disease Severity Score (PSDSS) in 1,013
      Patients with Colorectal Cancer with Peritoneal Carcinomatosis.
AB  - BACKGROUND: Extensive clinical experience suggests that hyperthermic
      intraperitoneal chemotherapy (HIPEC) may play an important role in the management
      of colorectal cancer patients with peritoneal carcinomatosis (CRCPC). However,
      there remains no established nonsurgical process to rationally select patients
      for this management, either for inclusion/stratification in clinical trials or as
      a component of standard of care. The Peritoneal Surface Disease Severity Score
      (PSDSS) was introduced as a basis to improve patient selection. METHODS: The
      American Society of Peritoneal Surface Malignancies conducted a retrospective
      review of 1,013 CRCPC patients. The PSDSS was evaluated on 3 specific criteria
      obtained before surgery (symptoms, extent of peritoneal dissemination, and
      primary tumor histology). Overall survival was analyzed according to four tiers
      of disease severity, and a comparison was made between patients who underwent
      cytoreductive surgery + HIPEC and those who did not. RESULTS: The PSDSS was
      calculated on 884 patients (87 %). The median survival of 275 patients not
      undergoing CRS/HIPEC based on their PSDSS-I (n = 8), II (n = 80), III (n = 55),
      and IV (n = 132)-was 45, 19, 8, and 6 months, respectively. The median survival
      of 609 patients who underwent CRS/HIPEC based on their PSDSS-I (n = 75), II (n =
      317), III (n = 82), and IV (n = 135)-was 86, 43, 29, and 28 months, respectively.
      CONCLUSIONS: These data support that the PSDSS, undertaken before surgery, is
      capable of defining CRCPC populations who have a statistically defined high or
      considerably lower likelihood of long-term survival after CRS/HIPEC. The PSDSS
      can be quite useful in the decision to enter CRCPC patients into, and their
      stratification within, clinical trials.

PMID- 24854494
TI  - Distantiae transmission of Trypanosoma cruzi: a new epidemiological feature of
      acute Chagas disease in Brazil.
AB  - BACKGROUND: The new epidemiological scenario of orally transmitted Chagas disease
      that has emerged in Brazil, and mainly in the Amazon region, needs to be
      addressed with a new and systematic focus. Belem, the capital of Para state,
      reports the highest number of acute Chagas disease (ACD) cases associated with
      the consumption of acai juice. METHODOLOGY/PRINCIPAL FINDINGS: The wild and
      domestic enzootic transmission cycles of Trypanosoma cruzi were evaluated in the
      two locations (Jurunas and Val-de Caes) that report the majority of the
      autochthonous cases of ACD in Belem city. Moreover, we evaluated the enzootic
      cycle on the three islands that provide most of the acai fruit that is consumed
      in these localities. We employed parasitological and serological tests throughout
      to evaluate infectivity competence and exposure to T. cruzi. In Val-de-Caes, no
      wild mammal presented positive parasitological tests, and 56% seroprevalence was
      observed, with low serological titers. Three of 14 triatomines were found to be
      infected (TcI). This unexpected epidemiological picture does not explain the high
      number of autochthonous ACD cases. In Jurunas, the cases of ACD could not be
      autochthonous because of the absence of any enzootic cycle of T. cruzi. In
      contrast, in the 3 island areas from which the acai fruit originates, 66.7% of
      wild mammals and two dogs displayed positive hemocultures, and 15.6% of
      triatomines were found to be infected by T. cruzi. Genotyping by mini-exon gene
      and PCR-RFLP (1f8/Akw21I) targeting revealed that the mammals and triatomines
      from the islands harbored TcI and Trypanosoma rangeli in single and mixed
      infections. CONCLUSION/SIGNIFICANCE: These findings show that cases of Chagas
      disease in the urban area of Belem may be derived from infected triatomines
      coming together with the acai fruits from distant islands. We term this new
      epidemiological feature of Chagas disease as "Distantiae transmission".

PMID- 24854495
TI  - 'Men usually say that HIV testing is for women': gender dynamics and perceptions
      of HIV testing in Lesotho.
AB  - In Lesotho, men have lower HIV testing rates, less contact with HIV clinical
      settings and less knowledge of HIV prevention than women. However, women's HIV
      prevalence has consistently remained higher than men's. This paper explores
      gender norms, sexual decision-making and perceptions of HIV among a sample of
      Basotho men and women in order to understand how these factors influence HIV
      testing and prevention. A total of 200 women and 30 men were interviewed in
      Lesotho between April and July 2011. Participants reported reluctance among women
      to share information about HIV prevention and testing with men, and resistance of
      men to engage with testing and/or prevention services. Findings demonstrate a
      critical need for educational initiatives for men, among other strategies, to
      engage men with HIV testing and prevention. This study highlights how gender
      issues shape perceptions of HIV and sexual decision-making and underlines the
      importance of engaging men along with women in HIV prevention efforts. More
      studies are needed to determine the most effective strategies to inform and
      engage men. 

PMID- 24854498
TI  - Tricks for tract dilation study.

PMID- 24854496
TI  - HbA1c can be a useful glycemic control marker for patients with neonatal diabetes
      mellitus older than 20 weeks of age.
AB  - BACKGROUND: The accuracy of most HbA1c analysis methods is affected by the
      presence of increased fetal hemoglobin (HbF). The objective of this study was to
      investigate the age at which HbA1c measurements become useful for monitoring
      glycemic control in patients with neonatal diabetes mellitus (NDM). METHODS: We
      retrospectively analyzed the data of 5 NDM patients diagnosed at 38+/-20 days of
      age, who each had several available HbA1c measurements during the first year of
      life, with a control group of HbA1c values over the course of 1 year for 13
      patients with type 1 diabetes mellitus (T1DM). Mean blood glucose (MBG) levels
      derived from premeal or premeal plus bedtime blood glucose measurements prior to
      HbA1c measurements were compared to HbA1c values. RESULTS: The NDM patients' age
      at which the difference in the HbA1c/MBG ratios became not significant between
      the NDM patients and the T1DM patients was 21 weeks of age and over. Even after
      the HbA1c was adjusted for HbF, this ratio was significantly lower in the NDM
      patients at <21 weeks of age than in the T1DM patients. CONCLUSIONS: HbA1c can be
      a useful glycemic control marker for NDM patients >20 weeks of age.

PMID- 24854500
TI  - Variation of surface ozone in Campo Grande, Brazil: meteorological effect
      analysis and prediction.
AB  - The effect of meteorological variables on surface ozone (O3) concentrations was
      analysed based on temporal variation of linear correlation and artificial neural
      network (ANN) models defined by genetic algorithms (GAs). ANN models were also
      used to predict the daily average concentration of this air pollutant in Campo
      Grande, Brazil. Three methodologies were applied using GAs, two of them
      considering threshold models. In these models, the variables selected to define
      different regimes were daily average O3 concentration, relative humidity and
      solar radiation. The threshold model that considers two O3 regimes was the one
      that correctly describes the effect of important meteorological variables in O3
      behaviour, presenting also a good predictive performance. Solar radiation,
      relative humidity and rainfall were considered significant for both O3 regimes;
      however, wind speed (dispersion effect) was only significant for high
      concentrations. According to this model, high O3 concentrations corresponded to
      high solar radiation, low relative humidity and wind speed. This model showed to
      be a powerful tool to interpret the O3 behaviour, being useful to define policy
      strategies for human health protection regarding air pollution. 

PMID- 24854499
TI  - Effect of organic amendments on the mobility of trace elements in phytoremediated
      techno-soils: role of the humic substances.
AB  - The efficiency of aided phytostabilization using organic amendments such as
      ramial chipped wood (RCW) and composted sewage sludge (CSS) was studied on
      contaminated techno-soils, on nine experimental plots. The objective was to
      characterize the role of fulvic (FA) and humic acids (HA) on the mobilization of
      trace elements, specifically As, Cu, Mo, Pb and Zn. Results showed that the
      addition of CSS increased the total organic carbon and nitrogen content more than
      with RCW and as a result, the C/N ratio in the CSS soil was higher than in the
      RCW and non-amended (NE) soil, reflecting the high decomposition of soil organic
      matter in the CSS soil compared with the other soils. The RCW and CSS amendments
      increased the hydrogen index (HI) values and the oxygen index (OI) values
      compared with the NE soil, especially for the soil treated with CSS which
      contained more aliphatic than aromatic compounds. The addition of CSS to the
      techno-soil significantly increased the percentage of C org associated with the
      HA fractions compared with the RCW and NE soils. The soil amended with CSS showed
      the highest E 4/E 6 ratio and the lowest E 2/E 3 ratio of FA. Zn and As were more
      abundant in the FA fraction than in the HA fraction, whereas Pb, Cu and Mo were
      more associated to HA than to FA in the treated and untreated soils, which may
      explain the difference in their mobility and availability. 

PMID- 24854501
TI  - EDTA ameliorates phytoextraction of lead and plant growth by reducing
      morphological and biochemical injuries in Brassica napus L. under lead stress.
AB  - Brassica species are very effective in remediation of heavy metal contaminated
      sites. Lead (Pb) as a toxic pollutant causes number of morphological and
      biochemical variations in the plants. Synthetic chelator such as
      ethylenediaminetetraacetic acid (EDTA) improves the capability of plants to
      uptake heavy metals from polluted soil. In this regard, the role of EDTA in
      phytoextraction of lead, the seedlings of Brassica napus L. were grown
      hydroponically. Lead levels (50 and 100 MUM) were supplied alone or together with
      2.5 mM EDTA in the nutrient culture. After 7 weeks of stress, plants indicated
      that toxicity of Pb caused negative effects on plants and significantly reduced
      growth, biomass, chlorophyll content, gas exchange characteristics, and
      antioxidant enzymes activities such as superoxide dismutase (SOD), guaiacol
      peroxidase (POD), ascorbate peroxidase (APX), and catalase (CAT). Exposure to Pb
      induced the malondialdehyde (MDA), and hydrogen peroxide (H2O2) generation in
      both shoots and roots. The addition of EDTA alone or in combination with Pb
      significantly improved the plant growth, biomass, gas exchange characteristics,
      chlorophyll content, and antioxidant enzymes activities. EDTA also caused
      substantial improvement in Pb accumulation in Brassica plants. It can be deduced
      that application of EDTA significantly lessened the adverse effects of lead
      toxicity. Additionally, B. napus L. exhibited greater degree of tolerance against
      Pb toxicity and it also accumulated significant concentration of Pb from media.

PMID- 24854502
TI  - Social determinants of community health services utilization among the users in
      China: a 4-year cross-sectional study.
AB  - BACKGROUND: To identify social factors determining the frequency of community
      health service (CHS) utilization among CHS users in China. METHODS: Nationwide
      cross-sectional surveys were conducted in 2008, 2009, 2010, and 2011. A total of
      86,116 CHS visitors selected from 35 cities were interviewed. Descriptive
      analysis and multinomial logistic regression analysis were employed to analyze
      characteristics of CHS users, frequency of CHS utilization, and the socio
      demographic and socio-economic factors influencing frequency of CHS utilization.
      RESULTS: Female and senior CHS clients were more likely to make 3-5 and >=6 CHS
      visits (as opposed to 1-2 visits) than male and young clients, respectively. CHS
      clients with higher education were less frequent users than individuals with
      primary education or less in 2008 and 2009; in later surveys, CHS clients with
      higher education were the more frequent users. The association between frequent
      CHS visits and family income has changed significantly between 2008 and 2011. In
      2011, income status did not have a discernible effect on the likelihood of making
      >=6 CHS visits, and it only had a slight effect on making 3-5 CHS visits.
      CONCLUSION: CHS may play an important role in providing primary health care to
      meet the demands of vulnerable populations in China. Over time, individuals with
      higher education are increasingly likely to make frequent CHS visits than
      individuals with primary school education or below. The gap in frequency of CHS
      utilization among different economic income groups decreased from 2008 to 2011.

PMID- 24854503
TI  - Does evidence drive pharmacist over-the-counter product recommendations?
AB  - RATIONALE, AIMS AND OBJECTIVES: To explore how community pharmacists use evidence
      to inform their practice when recommending or selling over-the-counter medicines.
      METHODS: Semi-structured face-to-face interviews were conducted during February
      2013 and analysed using the principles of content analysis. RESULTS: Sixteen
      pharmacists were interviewed. Pharmacists were aware of evidence-based medicine
      and practice but relied on personal judgement augmented with patient feedback to
      make product recommendations. This was primarily due to the acknowledgement that
      many non-prescription medicines either had no or little evidence of efficacy.
      Pharmacists did and would use evidence to inform product selection if available,
      but acknowledged that ineffective products were sold, especially when consumers
      asked for a named product. This was tempered by their attempts to inform the
      consumer of the products' effectiveness, or lack of, or in the knowledge that it
      would cause them no harm. CONCLUSIONS: Pharmacists took a pragmatic approach to
      product recommendation in light of the lack of clinical evidence to support their
      efficacy.

PMID- 24854504
TI  - Bullous eruption on the back of both hands in a newborn.

PMID- 24854505
TI  - Overcoming psychosocial and developmental barriers to blood and marrow
      transplantation (BMT) in an adolescent/young adult (AYA) transgender patient with
      chronic myelogenous leukemia.
AB  - Adolescents/young adults (AYAs) afflicted with cancer face unique barriers to
      potentially standard curative therapies, such as blood and marrow transplantation
      (BMT). Transgender AYAs face additional barriers and there is a dearth of
      published literature regarding their oncology-related experience. We present the
      case of an AYA male-to-female (MTF) transgender patient on cross-sex hormone
      therapy, with a history of Chronic Myelogenous Leukemia (CML) and significant
      psychosocial barriers, which initially served as a barrier to BMT at two
      different centers; we modified our standard consent and education process and was
      able to successfully proceed with BMT and subsequently cure her CML. Despite
      unique challenges, AYA and transgender patients with significant psychosocial
      barriers may achieve successful outcomes with BMT. Research is needed regarding
      guidelines for cross-sex hormone therapy administration for patients undergoing
      BMT and other issues, which may be unique to the transgender experience. 

PMID- 24854515
TI  - Response to a letter commenting on "vitamin D deficiency in Crohn's disease and
      healthy controls: a prospective case-control study in The Netherlands".

PMID- 24854516
TI  - HPV genotype prevalence in Australian women undergoing routine cervical screening
      by cytology status prior to implementation of an HPV vaccination program.
AB  - BACKGROUND: Data on the prevalence of cervical HPV genotypes in Australia by age
      and by grade of cytological abnormality are sparse. OBJECTIVE: Measure prevalence
      of HPV genotypes among 2620 Australian women by age and cytology status. STUDY
      DESIGN: Women presenting for routine Pap smear screening were recruited from
      diverse regions, including a significant sample of Indigenous women. DNA extracts
      prepared from Thinprep specimens were HPV genotyped by Roche LINEAR ARRAY HPV.
      RESULTS: HPV prevalence and genotype distribution were stratified by age (mean
      32.6y) and Pap smear result (cytology normal in 86.7%). Overall HPV prevalence
      was 38.7% with high-risk HPV prevalence of 26.5%. Prevalence of HPV (66.3% in
      women<21y to 15.3% in women>40y), multiple HPV infection (45.5% in <21y to 5.8%
      in >40y) and vaccine-targeted genotypes (HPV 6/11/16/18) (34.1% in <21y to 2.4%
      in >40y) declined significantly with age. The six most common genotypes were: HPV
      16 (8.3%), 51 (5.1%), 53 (4.7%), 62 (4.3%), 89 (3.9%) and 52 (3.8%). HR-HPV
      prevalence increased from 21.1% in women with normal cytology to 80.9% in those
      with cytologically predicted high-grade abnormalities (HGAs) (p<0.001). The most
      common genotypes in women with HGAs were HPV 16 (51.1%), 18 (14.9%), 52 (12.8%),
      31 (10.6%), and 33 (10.6%): all HR-types. CONCLUSION: Pre-vaccination cross
      sectional prevalence of HR-HPV infection was high in this sample of Australian
      women attending for screening. HPV 16 was the commonest high-risk type detected
      at all ages and cytological grades.

PMID- 24854517
TI  - Methods for multiplex template sampling in digital PCR assays.
AB  - The efficient use of digital PCR (dPCR) for precision copy number analysis
      requires high concentrations of target molecules that may be difficult or
      impossible to obtain from clinical samples. To solve this problem we present a
      strategy, called Multiplex Template Sampling (MTS), that effectively increases
      template concentrations by detecting multiple regions of fragmented target
      molecules. Three alternative assay approaches are presented for implementing MTS
      analysis of chromosome 21, providing a 10-fold concentration enhancement while
      preserving assay precision. 

PMID- 24854518
TI  - Myotonic dystrophy diagnosed after cesarean section.

PMID- 24854514
TI  - Correlation between AcrB trimer association affinity and efflux activity.
AB  - The majority of membrane proteins function as oligomers. However, it remains
      largely unclear how the oligomer stability of protein complexes correlates with
      their function. Understanding the relationship between oligomer stability and
      activity is essential to protein research and to virtually all cellular processes
      that depend on the function of protein complexes. Proteins make lasting or
      transient interactions as they perform their functions. Obligate oligomeric
      proteins exist and function exclusively at a specific oligomeric state. Although
      oligomerization is clearly critical for such proteins to function, a direct
      correlation between oligomer affinity and biological activity has not yet been
      reported. Here, we used an obligate trimeric membrane transporter protein, AcrB,
      as a model to investigate the correlation between its relative trimer affinity
      and efflux activity. AcrB is a component of the major multidrug efflux system in
      Escherichia coli. We created six AcrB constructs with mutations at the
      transmembrane intersubunit interface, and we determined their activities using
      both a drug susceptibility assay and an ethidium bromide accumulation assay. The
      relative trimer affinities of these mutants in detergent micelles were obtained
      using blue native polyacrylamide gel electrophoresis. A correlation between the
      relative trimer affinity and substrate efflux activity was observed, in which a
      threshold trimer stability was required to maintain efflux activity. The trimer
      affinity of the wild-type protein was approximately 3 kcal/mol more stable than
      the threshold value. Once the threshold was reached, an additional increase of
      stability in the range observed had no observable effect on protein activity.

PMID- 24854519
TI  - Anesthetic management of pulmonary valve replacement for pulmonary regurgitation
      in six patients with surgically repaired tetralogy of Fallot.
AB  - Tetralogy of Fallot (TOF) is the most common form of cyanotic congenital heart
      disease (CHD) encountered in CHD patients surviving into adulthood. A number of
      patients with surgically repaired TOF have significant pulmonary regurgitation
      (PR) that can lead to right ventricular (RV) dilatation, RV failure, and
      arrhythmia. We describe the anesthetic management for pulmonary valve replacement
      (PVR) in six PR patients with surgically repaired TOF. Although all patients had
      dilated RVs and depression of RV ejection fraction preoperatively, and arrhythmia
      and unexpected bleeding perioperatively, they could tolerate a well-managed PVR
      operation. Anesthesiologists should be aware of the multiplicity of
      comorbidities, sequelae, and residua in patients with surgically repaired TOF. RV
      function should be monitored using transesophageal echocardiography, and
      inotropic vasodilators and alpha-adrenergic agents should be administered, as
      appropriate. Arrhythmias, vascular injury during removal of adhesions during re
      sternotomy, and bleeding from collateral vessels are also frequent complications.

PMID- 24854520
TI  - Condensation of humidified air in the inflation line of a polyurethane cuff
      precludes correct continuous pressure monitoring during mechanical ventilation.
AB  - Within continuously controlled limits of cuff pressure, an endotracheal tube cuff
      made of polyurethane (PU) prevents secretion inflow better than a conventional
      polyvinylchloride cuff. However, the temperature difference between ventilator
      gas and the air inside a PU cuff produces condensation droplets that accumulate
      in the cuff inflation canal. We investigated whether condensation influenced
      continuous cuff pressure monitoring. A PU-cuffed tube was placed into an
      artificial trachea and connected to a ventilator and test lung. An additional
      line was inserted at the distal cuff end to directly measure pressure inside the
      cuff. Methylene blue instillation via the inflation line mimicked condensation.
      Inspiratory (Pinsp) and expiratory (Pexp) pressures were continuously recorded.
      Six consecutive experiments were performed comparing pressures at baseline (T0)
      and at 24 h (T24). Shortly after dye instillation, pressures recorded at the
      inflation canal became permanently fixed at 25 cmH2O. In contrast, pressures
      measured directly in the cuff progressively decreased (mean Pinsp 30 +/- 3 vs. 20
      +/- 2 cmH2O and mean Pexp 25 +/- 0 vs. 12 +/- 2 cmH2O, T0 vs. T24, both P <
      0.05). Thus, condensation in the inflation line of a PU-cuffed tube renders
      continuous cuff pressure monitoring unreliable, thereby increasing the risk for
      microaspiration.

PMID- 24854521
TI  - Dexmedetomidine suppresses long-term potentiation in the hippocampal CA1 field of
      anesthetized rats.
AB  - PURPOSE: The aim of this study was to evaluate the effect of dexmedetomidine
      (DEX) on hippocampal synaptic activity in vivo. METHODS: The adult rats used for
      this study received a intraperitoneal bolus injection of 3, 10, 30, or 100 MUg/kg
      of DEX or an equivalent volume of saline. Electrophysiological recording of the
      hippocampal CA1 region was initiated 20 min after drug administration. The
      results are expressed as the percentages of the population spike amplitude
      measured just before high-frequency stimulation (HFS). The electrophysiological
      data were analyzed with an area under the curve (AUC) of 10-60 min after HFS.
      Moreover, to investigate the sedative dose of DEX in rats, we recorded the
      duration of loss of spontaneous movement after the administration of each dose of
      DEX. RESULTS: Intraperitoneal administration of DEX at doses of 30 and 100 MUg/kg
      induced a range of sedative effects. The AUC measurements were significantly
      lower in the 30 and 100 MUg/kg groups than in those injected with vehicle
      (vehicle: 8.81 +/- 0.49, n = 7; DEX 30 ug/kg: 6.02 +/- 0.99, n = 6; DEX 100
      ug/kg: 5.10 +/- 0.43, n = 5; P < 0.05). CONCLUSION: The results of our in vivo
      study reveal that sedative doses of DEX impaired the induction of hippocampal
      long-term potentiation (LTP). These findings may signify a causal link between
      DEX-induced sedative action and hippocampal LTP suppression, providing a better
      understanding of the mechanisms underlying the DEX-induced sedative and/or
      amnestic effect.

PMID- 24854522
TI  - Cushing's syndrome: hidden risk in usage of topical corticosteroids.
AB  - Iatrogenic Cushing's syndrome in children may occur as a result of the
      application of exogenous steroids. Prolonged use of powerful corticosteroids
      suppresses adrenal functions and iatrogenic Cushing's syndrome may develop
      particularly in infants who are given topical corticosteroids. We report here a
      case on three infants having Cushing's syndrome with similar clinical
      presentations due to overuse of topical steroids for diaper dermatitis. The
      importance of exercising caution during the use of topical steroids is underlined
      in this study.

PMID- 24854523
TI  - The evaluation of thyroid carcinoma in childhood and concomitance of autoimmune
      thyroid disorders.
AB  - Autoimmune thyroiditis has been suggested as a precancerous condition in some
      adult studies, but there is still controversy. The importance of autoimmune
      thyroiditis in childhood thyroid cancer is not yet completely clear. We aimed to
      evaluate in this study the characteristics of childhood thyroid cancer in
      patients particularly in terms of coexisting factors including autoimmune thyroid
      disorders (ATD). Twenty patients diagnosed with primary thyroid cancer were
      evaluated retrospectively in a Pediatric Endocrinology clinic for 10 years.
      Patients were followed up for 57.22+/-11 months. Concomitant conditions
      (thyroidal and/or extra thyroidal) were determined. Most of the patients (80%)
      had a coexisting factor. ATDs are the most frequently encountered among them
      (40%). The ages at the time of diagnosis were older; and the tumor sizes were
      smaller in patients with concomitant ATDs than without autoimmune thyroid
      disorders. The follow-up characteristics were similar in both groups. In
      conclusion, ATDs are frequently encountered in association with thyroid cancer
      during childhood and adolescence. A thyroid autoimmunity may facilitate the
      development of a malignant thyroid tumor; on the other hand, increased attention
      to the thyroid gland may facilitate frequent diagnosis of thyroid cancer. A close
      follow-up of ATD patients should also include the evaluation of the development
      of thyroid malignancy.

PMID- 24854524
TI  - Assessment of aortic morphology and compliance in children and adolescents with
      Ullrich-Turner syndrome (UTS) using magnetic resonance imaging (MRI).
AB  - AIM: The aim of this study was to evaluate the morphology and elastic properties
      of the aorta in children and adolescents with Ullrich-Turner syndrome (UTS)
      treated with growth hormone, by using magnetic resonance imaging (MRI). METHODS:
      Thirty-seven conscious UTS patients were examined using a 1.5-T whole-body MRI.
      Contrast-free three-dimensional (3D)-MR angiographies were performed, including
      2D cine MRI, to calculate the aortic compliance (C) and cine of the aortic valve.
      RESULTS: Changes of aortic morphology were evident in 40% of the patients,
      whereas six had more than one alteration. A bicuspid aortic valve was identified
      in three patients that were missed by previous echocardiography. The aortic
      compliances in UTS patients were similar to those in healthy persons. CONCLUSION:
      This study shows that aortic morphology and compliance can be assessed by MRI
      without using contrast agents and without sedation in children and adolescents
      with UTS.

PMID- 24854525
TI  - A novel CASR mutation associated with neonatal severe hyperparathyroidism
      transmitted as an autosomal recessive disorder.
AB  - BACKGROUND: Neonatal severe primary hyperparathyroidism (NSHPT, MIM 239200) is
      most often an isolated disorder that is due to biallelic inactivating mutations
      in the CASR, the gene encoding the calcium sensing receptor; NSHPT is inherited
      from parents with familial hypocalciuric hypercalcemia, each of whom has one
      mutated CASR allele. OBJECTIVES: To report clinical and genetic findings in a
      brother and sister with NSHPT due to a novel mutation in the CASR transmitted as
      an autosomal recessive trait and to examine the functional effect of the
      mutation. SUBJECTS AND METHODS: A brother and sister with marked hypercalcemia
      due to NSHPT were identified; the boy also had craniosynostosis requiring
      surgical repair. The genotyping of the CASR in both children and their parents
      who were eucalcemic and normophosphatemic was undertaken. In order to examine the
      significance of the variant CASR identified, the CASR variant was expressed in
      vitro and examined by three computer computational programs [PolyPhen2,
      MutationTaster, Sorting Intolerant From Tolerant (SIFT)] designed to evaluate the
      effect of a nucleotide variant on the structure and likely functional consequence
      upon the protein product. RESULTS: A sequence variant in the CASR was identified
      [G>T point mutation at nucleotide c.2303 in exon 7 (c.2303G>T) resulting in the
      replacement of glycine by valine at codon 768 (p.Gly768Val)]. Two copies of this
      CASR variant were present in the genome of the siblings while a single copy of
      the CASR variant was present in both of the clinically and biochemically normal
      parents, a pattern of transmission consistent with autosomal recessive
      inheritance of NSHPT in this family. When expressed in HEK293 cells in vitro, the
      novel Gly768Val variant did not interfere with protein generation or migration to
      the cell membrane in vitro. The analysis of the functional effect of the
      Gly768Val CASR variant by the PolyPhen2, MutationTaster, and Sorting Intolerant
      From Tolerant computer programs revealed that this mutation was very likely to be
      deleterious. CONCLUSION: The NSHPT associated with biallelic Gly768Val mutations
      of the CASR in two siblings with severe hypercalcemia and hyperparathyroidism and
      their clinically and biochemically normal heterozygous parents was transmitted as
      an autosomal recessive disorder in this family.

PMID- 24854526
TI  - The role of anti-Mullerian and inhibin B hormones in the evaluation of 46,XY
      disorders of sex development.
AB  - OBJECTIVE: To assess the sensitivity and specificity of anti-Mullerian hormone
      (AMH) and inhibin B for diagnosis of 46,XY disorders of sex development (DSD).
      PATIENTS AND METHODS: The study included 43 patients of 46,XY DSD and compared
      them with 43 healthy, male, age matched controls. All patients underwent
      karyotyping, assessment of testosterone, dihydrotestosterone (DHT) and Delta4
      androstendione (Delta4A) basal and after human chorionic gonadotropin (HCG)
      testing. Basal dehydroepiandrosterone (DHEA) was measured. Ultrasonograghy was
      also done and some cases underwent laparoscopy or gonadal biopsies. Basal AMH and
      inhibin B were measured in both cases and controls. RESULTS: The mean age of
      patients was 5.16+/-4.24 years. There were significant correlations between basal
      AMH and HCG stimulated testosterone and DHT (r=0.64; p<0.001 and r=0.52; p<0.001,
      respectively). Also, significant positive correlations were found between inhibin
      B and HCG as well as stimulated testosterone and DHT (r=0.62; p<0.001 and r=0.44;
      p=0.003, respectively). A highly significant correlation was found between AMH
      and inhibin B (r=0.78; p<0.001). The sensitivity of AMH was (96.6%), specificity
      (60.7%), NPV (89.5%) and PPV (83.6%). Best cut-off value was (27.11 IU/mL) while
      overall accuracy was (85%). The sensitivity of inhibin B was (96.6%), specificity
      (67.9%), NPV (90.5%), PPV (86.2%), and best cut-off value was (41.9 IU/mL) with
      an overall accuracy (87%). CONCLUSION: AMH and inhibin B are valuable, and
      reliable noninvasive parameters for the detection of functioning testicular
      tissues in prepubertal patients.

PMID- 24854528
TI  - The effect of adenotonsilectomy on ghrelin, leptin, IGF-1 levels and growth
      parameters in children with adenotonsillar hypertrophy.
AB  - AIM: The purpose of this study was to search for the effects of
      adenotonsillectomy (A&T) on height, weight, and body mass index (BMI), as well as
      changes in ghrelin, leptin, and insulin-like growth factor 1 (IGF-1) levels in
      children with adenotonsillar hypertrophy (ATH)-related sleep-disordered breathing
      (SDB). METHODS: A study cohort of 39 children clinically diagnosed with ATH
      related SDB was included in this study. Twenty-three healthy children were
      included as controls. Height and weight standard deviation scores (SDS) and
      ghrelin, leptin, and IGF-1 levels of the controls were determined once; in the
      study group, they were determined preoperatively and in the third month
      postoperatively. RESULTS: Preoperative IGF-1 (ng/mL) and ghrelin (pg/mL) levels
      were significantly higher in the patients than in the controls (322.51+/-113.10
      vs. 256.96+/-176.73, p<0.05 and 106.08+/-9.75 vs. 80.11+/-28.50, p<0.001,
      respectively). The preoperative height and weight SDS values of the patients were
      lower than those of the controls (-0.67+/-1.36 vs. 0.13+/-1.13, p<0.05 and 
      0.38+/-1.35 vs. -0.20+/-1.29, respectively). The patients' postoperative height
      and weight SDS values were significantly higher than their preoperative values (
      0.05+/-1.08 vs. -0.67+/-1.36, p<0.0001 and 0.00+/-1.28 vs. -0.38+/-1.35,
      p<0.0001, respectively). The mean postoperative IGF-1 levels also were
      significantly higher than preoperative levels (386.05+/-130.06 vs. 322.51+/
      113.10, p<0.05, respectively). CONCLUSION: Plasma IGF-1 levels are lower in
      malnourished children, and plasma ghrelin levels are decreased after acute oral
      food intake and are increased in cachexia and fasting. Therefore, increased serum
      IGF-1 levels, height and weight SDS values, and decreased ghrelin levels detected
      postoperatively are useful parameters that help to monitor the development of
      children with adequate oral intakes.

PMID- 24854527
TI  - Maternal factors and complications of preterm birth associated with neonatal
      thyroid stimulating hormone.
AB  - Thyroid hormones are important regulators of fetal neurodevelopment. Among
      preterm infants, thyroid stimulating hormone (TSH) is highly variable.
      Understanding this variability will further improvements in screening for thyroid
      disorders in preterm infants. We examined 61 maternal and infant clinical and
      demographic factors for associations with neonatal TSH levels in 698 preterm
      neonates. TSH was measured as part of routine State-mandated newborn screening in
      Iowa. Of the maternal characteristics, nulliparous women (p=8*10-4), women with
      preeclampsia (p=2*10-3), and those with induced labor (p=3*10-3) had infants with
      higher TSH levels. TSH levels at the time of newborn screening were associated
      with respiratory distress syndrome (RDS) (p<0.0001) and sepsis (p=3*10-3). We
      replicated findings between parity and preeclampsia previously observed in
      primarily term infants. We also observed strong relationships between neonatal
      TSH and complications of prematurity including RDS and sepsis, which have
      implications for future studies examining this relationship both prenatally and
      longitudinally after birth.

PMID- 24854529
TI  - Management of central diabetes insipidus with oral desmopressin lyophilisate in
      infants.
AB  - AIM: To assess the efficiency of oral desmopressin lyophilisate (ODL) in neonatal
      central diabetes insipidus (CDI). METHODS: The characteristics of four newborns
      with CDI treated with ODL were evaluated. RESULTS: Four newborns with polyuria
      and hypernatremia were included [male, 2 (50%); mean postnatal age, 19+/-17
      days]. At the time of hypernatremia, the mean serum and urine osmolality values
      were 310+/-16 and 179+/-48 mOsm/kg, respectively. Antidiuretic hormone levels
      were undetectable (<0.5 pmol/L) in all cases. Magnetic resonance imaging revealed
      anatomical malformations in all cases. ODL (60 MUg/tablet) dissolved in water (3
      5 mL) was initiated with a dose of 5 MUg/kg/day in two equal doses, together with
      limitation of water intake to avoid hyponatremia. Serum sodium levels returned to
      normal in a mean duration of 58+/-9.9 h with a mean decline rate of 0.37+/-0.1
      mEq/L/h after desmopressin administration. Rehospitalization was required for one
      of the infants because of hypernatremia due to non-compliance. No episode of
      hyponatremia was encountered. Weight gain and growth of the infants were normal
      during the mean follow-up duration of 8.5+/-1 months. CONCLUSIONS: ODL appears to
      be practical and safe in the treatment of CDI during the first year of life.

PMID- 24854532
TI  - Clinical applicability of rapid detection of SRY and DYS14 genes in patients with
      disorders of sex development using an indigenously developed 5' exonuclease based
      assay.
AB  - BACKGROUND: Life threatening conditions are associated with atypical genitalia in
      newborns. Analysis of genetic sex provides a clue to the underlying etiology in
      newborns with disorders of sex development (DSD) and can guide further endocrine
      investigations. Rapid diagnosis of genetic sex would be immensely useful in this
      situation. Traditionally used methods such as karyotype and fluorescence in situ
      hybridisation are time-consuming. OBJECTIVES: To study the clinical applicability
      of an indigenously developed rapid real-time polymerase chain reaction (RT-PCR)
      assay for the sex determining region on the Y chromosome (SRY gene) and the DYS14
      locus in newborns with DSD. METHODS: Clinical examination, endocrinological
      tests, RT-PCR analysis of SRY and DYS14 and karyotype was performed in 15
      newborns with DSD. RESULTS: RESULTS of PCR were available within 4 h. Based on
      this report, in SRY/DYS14 positive cases, further tests for assessment of
      testicular function were done. In SRY negative cases, tests for congenital
      adrenal hyperplasia were done. On comparing PCR results with other tests, the Y
      chromosome was present on karyotype and testicular tissue was detected by
      endocrinological and/or histological methods in all (8/15) SRY positive cases.
      The SRY and DYS14 negative cases (7/15) did not have Y chromosome in the
      karyotype. Congenital adrenal hyperplasia (CAH) was the most common diagnosis in
      this group. CONCLUSIONS: The indigenously developed PCR for dual Y chromosome
      markers is rapid and sensitive. Further endocrine evaluation of newborns with DSD
      can be based on these results. Information of genetic sex partly allays the
      psychosocial distress associated with the condition.

PMID- 24854531
TI  - Multiple autoimmunity, type 1 diabetes (T1DM), autoimmune thyroiditis and thyroid
      cancer: is there an association? A case report and literature review.
AB  - Type 1 diabetes mellitus (T1DM) is characterized by selective autoimmune
      destruction of pancreatic b-cells, resulting in insulin deficiency. Associated
      autoimmune disorders, such as celiac disease, autoimmune thyroiditis, and
      gastritis, can coexist in patients with T1DM. These disorders are characterized
      by the presence of antibodies against tissue transglutaminase (anti-tTG-IgA),
      thyroglobulin, and thyroid peroxidase (anti-TG, anti-TPO), as well as antibodies
      against gastric parietal cells. Children with T1DM may also develop organ
      specific multiple autoimmunity, with the coexistence of one or more autoimmune
      disorders. Furthermore, there is a lot of controversy regarding the role of
      thyroid autoimmunity in the pathogenesis of thyroid cancer. We present a child
      with T1DM and multiple autoimmunity including autoimmune Hashimoto's thyroiditis
      (HT), who developed thyroid cancer. The literature on the prevalence of
      associated autoimmunity in children with T1DM and the prevalence, pathogenesis,
      and timely diagnosis of thyroid cancer among patients with HT is also reviewed.

PMID- 24854530
TI  - Counseling patients with succinate dehydrogenase subunit defects: genetics,
      preventive guidelines, and dealing with uncertainty.
AB  - The discovery that mutations in the succinate dehydrogenase (SDH) complex subunit
      (SDHA, B/C/D/AF2) genes predispose patients to the development of tumors has led
      to the identification of a large population of patients and relatives at risk for
      developing malignancies. The most frequent conditions associated with these
      mutations are the familial paraganglioma syndromes. Other tumors that are
      frequently associated with SDH mutations (SDHx) are gastrointestinal stromal
      tumors and renal cell carcinomas. A number of other rare associations have also
      been described. SDHx mutations are often clinically silent and metastatic, but
      they may also be aggressive in their presentation. The penetrance of these
      mutations is beginning to be understood, and the characteristics of the phenotype
      are being elucidated. However, the inability to accurately predict the
      appearance, nature, and location of tumors as well as their tendency to recur or
      metastasize pose challenges to those who counsel and manage patients with SDHx
      mutations. In this work, we present our approach for counseling these families in
      the context of the current uncertainties, while striving to maintain patient
      autonomy.

PMID- 24854534
TI  - Autonomic contributions in postural control: a review of the evidence.
AB  - The ability to maintain balance is critical for daily activities such as walking
      and fall avoidance. The contemporary models of postural control emphasize the
      central and somatic interactions engaged in maintaining balance; however, there
      is emerging evidence that the autonomic nervous system (ANS) - the sympathetic
      division, in particular - routinely participates in postural control. The purpose
      of this paper is to review the evidence demonstrating the autonomic interactions
      in postural control. These interactions are presented in two broad categories:
      those that conceptualize the maintenance of postural equilibrium as a component
      of bodily homeostasis and those that illustrate how changes in affective states
      link cognitive perceptions and physiological responses (in this case, balance).
      The shared commonalities between postural and autonomic pathways are presented,
      pointing to the areas of overlap and the potential sources of the interaction.
      Although the specific function of autonomic engagement in postural control
      remains unknown, the potential roles are explored and highlight the directions
      for continued study.

PMID- 24854533
TI  - Prevalence of vitamin D deficiency among Iranian adolescents.
AB  - OBJECTIVE: Despite the high prevalence of vitamin D deficiency in adults
      worldwide, not many studies have evaluated the condition in adolescents. The
      present study was therefore conducted to assess the prevalence of vitamin D
      deficiency in a group of students from Shahroud, Iran. METHODS: The cross
      sectional descriptive analytical study was conducted on junior high and high
      school students of both genders from urban and rural areas of Shahroud, the
      largest city of Semnan Province in Iran, in winter 2011. The combination of
      stratified and cluster random sampling methods was applied in the study. A
      questionnaire on the demographic data, socioeconomic status, lifestyle habits
      (sun exposure, physical activity, dairy consumption), and drug and personal
      history was completed for each student. Blood samples were taken to assess
      vitamin D levels. RESULTS: One thousand forty-seven students from four junior
      high and six high schools were recruited. From among them, 42.2% were boys and
      57.8% were girls. Mean and standard deviation of vitamin D levels in the studied
      population were 14.7 +/- 9.4 ng/mL. Only 7.2% of the boys and 3.8% of the girls
      had sensible sun exposure. The median of milk consumption was 3 glasses per week,
      ranging from 0 to 7. CONCLUSION: It could be concluded that vitamin D deficiency
      is quite prevalent among the Iranian adolescents, and this is mainly because this
      group follows an unhealthy lifestyle due to osteoporosis.

PMID- 24854535
TI  - Functions of the neuron-specific protein ADAP1 (centaurin-alpha1) in neuronal
      differentiation and neurodegenerative diseases, with an overview of structural
      and biochemical properties of ADAP1.
AB  - Eukaryotic cells express numerous ArfGAPs (ADP-ribosylation factor GTPase
      activating proteins). There is increasing knowledge about the function of the
      brain-specific protein ADAP1 [ArfGAP with dual pleckstrin homology (PH) domain]
      as well as about its biochemical properties. The ADAP subfamily, also designated
      centaurin-alpha, has an N-terminal ArfGAP domain followed by two PH domains. The
      mammalian ADAP subfamily consists of two identified isoforms, ADAP1 and ADAP2
      (centaurin-alpha1 and -alpha2). ADAP1 is highly expressed in neurons. We
      highlight the functional roles of ADAP1 in neuronal differentiation and
      neurodegeneration. Because of interactions with different proteins and
      phosphoinositol-lipids, ADAP1 can function as a scaffolding protein in several
      signal transduction pathways. Firstly, ADAP1 mediates cytoskeletal crosstalk.
      This is indicated by multiple interactions of ADAP1 with components of the actin
      and microtubule cytoskeleton. Secondly, regulation of neuronal polarity formation
      and axon specification by ADAP1 is suggested by crystal structural data obtained
      for human ADAP1, and the complexes of ADAP1-Ins(1,3,4,5)P4 and/or the forkhead
      associated domain of the kinesin KIF13B. These structures support the concept
      that a KIF13B-ADAP1 complex enhances the local accumulation of PtdIns(3,4,5)P3 at
      the tips of neurites, and thus favors neuronal polarity. Thirdly, recent evidence
      unravels a pathological role of ADAP1 because upregulation of ADAP1 by amyloid
      beta-peptide causes ADAP1-Ras-ERK-dependent translocation of Elk-1 to
      mitochondria. This impairs mitochondrial functions with subsequent synaptic
      dysfunction and exacerbates neurodegeneration, as in Alzheimer's disease.

PMID- 24854536
TI  - Putative kallikrein substrates and their (patho)biological functions.
AB  - Human tissue kallikreins (KLKs) represent the largest contiguous group of
      protease genes within our genome. All 15 KLK genes co-localize within
      approximately 260 kb in human chromosome 19q13.3-13.4 (14 640 kb->274 990 kb).
      They are widely expressed in several tissues and mediate a wide range of critical
      physiological and pathological processes. Despite the recent developments in KLK
      research, elucidation of their physiological substrate repertoires remains a
      largely unfulfilled goal. Phage display, positional scanning and combinatorial
      peptide library screens have provided some valuable insights into the preferred
      specificities of these powerful enzymes. More recently, advances in proteomic
      technologies have enabled more systemic approaches towards identification of KLK
      substrates in a physiological setting. The advent of degradomic technologies has
      brought to light several putative physiological substrates and has allowed a
      deeper appreciation of the in vivo functional roles of KLKs. The aim of this
      review is to provide an overview of the different techniques that have been
      utilized towards the elucidation of the substrate specificities of these enzymes
      and elaborate on their emerging in vivo substrates.

PMID- 24854537
TI  - Structural insights into calmodulin/Munc13 interaction.
AB  - Munc13 proteins are essential presynaptic regulators that mediate synaptic
      vesicle priming and play a role in the regulation of neuronal short-term synaptic
      plasticity. All four Munc13 isoforms share a common domain structure, including a
      calmodulin (CaM) binding site in their otherwise divergent N-termini. Here, we
      summarize recent results on the investigation of the CaM/Munc13 interaction. By
      combining chemical cross-linking, photoaffinity labeling, and mass spectrometry,
      we showed that all neuronal Munc13 isoforms exhibit similar CaM binding modes.
      Moreover, we demonstrated that the 1-5-8-26 CaM binding motif discovered in
      Munc13-1 cannot be induced in the classical CaM target skMLCK, indicating unique
      features of the Munc13 CaM binding motif.

PMID- 24854538
TI  - Selective modulation of plasmodial Hsp70s by small molecules with antimalarial
      activity.
AB  - Plasmodial heat shock protein 70 (Hsp70) chaperones represent a promising new
      class of antimalarial drug targets because of the important roles they play in
      the survival and pathogenesis of the malaria parasite Plasmodium falciparum. This
      study assessed a set of small molecules (lapachol, bromo-beta-lapachona and
      malonganenones A, B and C) as potential modulators of two biologically important
      plasmodial Hsp70s, the parasite-resident PfHsp70-1 and the exported PfHsp70-x.
      Compounds of interest were assessed for modulatory effects on the steady-state
      basal and heat shock protein 40 (Hsp40)-stimulated ATPase activities of PfHsp70
      1, PfHsp70-x and human Hsp70, as well as on the protein aggregation suppression
      activity of PfHsp70-x. The antimalarial marine alkaloid malonganenone A was of
      particular interest, as it was found to have limited cytotoxicity to mammalian
      cell lines and exhibited the desired properties of an effective plasmodial Hsp70
      modulator. This compound was found to inhibit plasmodial and not human Hsp70
      ATPase activity (Hsp40-stimulated), and hindered the aggregation suppression
      activity of PfHsp70-x. Furthermore, malonganenone A was shown to disrupt the
      interaction between PfHsp70-x and Hsp40. This is the first report to show that
      PfHsp70-x has chaperone activity, is stimulated by Hsp40 and can be specifically
      modulated by small molecule compounds.

PMID- 24854540
TI  - Activation of membrane-bound proteins and receptor systems: a link between tissue
      kallikrein and the KLK-related peptidases.
AB  - The 15 members of the kallikrein-related serine peptidase (KLK) family have
      diverse tissue-specific expression profiles and roles in a range of cellular
      processes, including proliferation, migration, invasion, differentiation,
      inflammation and angiogenesis that are required in both normal physiology as well
      as pathological conditions. These roles require cleavage of a range of
      substrates, including extracellular matrix proteins, growth factors, cytokines as
      well as other proteinases. In addition, it has been clear since the earliest days
      of KLK research that cleavage of cell surface substrates is also essential in a
      range of KLK-mediated cellular processes where these peptidases are essentially
      acting as agonists and antagonists. In this review we focus on these KLK
      regulated cell surface receptor systems including bradykinin receptors,
      proteinase-activated receptors, as well as the plasminogen activator, ephrins and
      their receptors, and hepatocyte growth factor/Met receptor systems and other
      plasma membrane proteins. From this analysis it is clear that in many
      physiological and pathological settings KLKs have the potential to regulate
      multiple receptor systems simultaneously; an important issue when these
      peptidases and substrates are targeted in disease.

PMID- 24854539
TI  - Low mRNA expression levels of kallikrein-related peptidase 4 (KLK4) predict short
      term relapse in patients with laryngeal squamous cell carcinoma.
AB  - Several members of the family of tissue kallikrein and kallikrein-related
      peptidases have been suggested as promising tumor biomarkers with important
      prognostic significance. However, only one (KLK11) has already been studied in
      laryngeal squamous cell carcinoma (LSCC) as a potential biomarker for LSCC
      diagnosis and/or prognosis. Our study investigated the prognostic value of
      kallikrein-related peptidase-4 (KLK4) mRNA expression as a molecular tissue
      biomarker in LSCC. For this purpose, KLK4 mRNA expression analysis was performed
      in 116 cancerous and 74 paired non-cancerous laryngeal tissue specimens obtained
      from patients that had undergone surgical treatment for primary LSCC. A
      remarkable downregulation of KLK4 mRNA expression was discovered in laryngeal
      tumors, compared to non-cancerous laryngeal tissue specimens. KLK4 mRNA
      expression was also shown to distinguish LSCC from non-cancerous laryngeal
      tissues. Furthermore, low KLK4 mRNA expression was shown to predict poor disease
      free survival, independently of the histological grade and size of the malignant
      tumor as well as patient TNM stage. According to Kaplan-Meier survival analysis,
      low KLK4 mRNA expression predicts short-term relapse even among patients with
      well-differentiated tumors or those at an early TNM stage. Thus, KLK4 mRNA
      positivity could be regarded as a novel independent indicator of favorable
      prognosis for the disease-free survival of LSCC patients.

PMID- 24854542
TI  - Diagnosis of diabetes mellitus: reiterated responsibilities for the clinical
      laboratory.

PMID- 24854541
TI  - Immune-modulating effects of alpha-1 antitrypsin.
AB  - Alpha-1 antitrypsin (AAT) is a circulating serine protease inhibitor (serpin)
      that inhibits neutrophil elastase in the lung, and AAT deficiency is associated
      with early-onset emphysema. AAT is also a liver-derived acute-phase protein that,
      in vitro and in vivo, reduces production of pro-inflammatory cytokines, inhibits
      apoptosis, blocks leukocyte degranulation and migration, and modulates local and
      systemic inflammatory responses. In monocytes, AAT has been shown to increase
      intracellular cAMP, regulate expression of CD14, and suppress NFkappaB nuclear
      translocation. These effects may be mediated by AAT's serpin activity or by other
      protein-binding activities. In preclinical models of autoimmunity and
      transplantation, AAT therapy prevents or reverses autoimmune disease and graft
      loss, and these effects are accompanied by tolerogenic changes in cytokine and
      transcriptional profiles and T cell subsets. This review highlights advances in
      our understanding of the immune-modulating effects of AAT and their potential
      therapeutic utility.

PMID- 24854543
TI  - The Living Well Lab: a community-based HIV/AIDS research initiative.
AB  - BACKGROUND: Complementary and Alternative Medicine (CAM) is becoming a pillar in
      the rehabilitative efforts for many living with HIV/AIDS. A community-based
      research program called the Living Well Lab (LWL) was established in 2007,
      operating out of Friends For Life (FFL), a non-profit wellness center in
      Vancouver, Canada offering free CAM therapies to people living with HIV/AIDS.
      Therapies range from naturopathy to yoga. The LWL partnered with academic and
      community organizations to evaluate CAM use and changes in health and quality of
      life outcomes of FFL's HIV+ members. METHODS: A longitudinal, combined methods
      approach assessed the health- and quality-of-life-related outcomes and
      experiences of CAM users. Participants completed outcome packages (5 time points)
      over 18 months, which focused on changes in physical and emotional states,
      satisfaction with services and social support. Interviews were conducted at
      baseline, 9- and 18-month time points. Quantitative analyses were descriptive
      while content analysis and thematic coding were used in the qualitative analysis.
      RESULTS: Two hundred and seven members enrolled in the LWL. Quantitative data
      demonstrated improvement in mental and physical wellbeing, social support and
      patient satisfaction specifically: SF-12, Arizona Integrative Outcomes Scale and
      three visual analog scales (stress, pain and energy). Participants felt several
      factors contributed to these changes such as managing anxiety, accepting their
      illness, learning to relax, an increased capacity for self-care and social
      support. CONCLUSIONS: CAM use may be associated with changes to physical, social
      and mental wellbeing. Issues throughout the study provided important lessons for
      future research.

PMID- 24854545
TI  - Chaperone protein involved in transmembrane transport of iron.
AB  - DMT1 (divalent metal transporter 1) is the main iron importer found in animals,
      and ferrous iron is taken up by cells via DMT1. Once ferrous iron reaches the
      cytosol, it is subjected to subcellular distribution and delivered to various
      sites where iron is required for a variety of biochemical reactions in the cell.
      Until now, the mechanism connecting the transporter and cytosolic distribution
      had not been clarified. In the present study, we have identified PCBP2 [poly(rC)
      binding protein 2] as a DMT1-binding protein. The N-terminal cytoplasmic region
      of DMT1 is the binding domain for PCBP2. An interaction between DMT1 and PCBP1,
      which is known to be a paralogue of PCBP2, could not be demonstrated in vivo or
      in vitro. Iron uptake and subsequent ferritin expression were suppressed by
      either DMT1 or PCBP2 knockdown. Iron-associated DMT1 could interact with PCBP2 in
      vitro, whereas iron-chelated DMT1 could not. These results indicate that ferrous
      iron imported by DMT1 is transferred directly to PCBP2. Moreover, we demonstrated
      that PCBP2 could bind to ferroportin, which exports ferrous iron out of the cell.
      These findings suggest that PCBP2 can transfer ferrous iron from DMT1 to the
      appropriate intracellular sites or ferroportin and could function as an iron
      chaperone. 

PMID- 24854546
TI  - Disease-specific impoverishment impact of out-of-pocket payments for health care:
      evidence from rural Bangladesh.
AB  - BACKGROUND: Analysing disease-specific impoverishment impact of out-of-pocket
      (OOP) payments for health care is crucial for priority setting in any informed
      policy discussion. Lack of evidence, particularly in the Bangladesh context,
      motivates our paper. OBJECTIVE: To examine disease-specific impoverishment impact
      of OOP payments for health care. METHODS: The paper estimates the poverty impact
      of OOP payments by comparing the difference between the average level of
      headcount poverty and poverty gap with and without health care payments. We used
      primary data drawn from 3,941 households, distributed over 120 villages of seven
      districts in Bangladesh during August-September 2009. FINDINGS: We find that OOP
      outlays annually push 3.4 % households into poverty. The corresponding figures
      for those who had non-communicable diseases (NCDs), chronic illness,
      hospitalization and catastrophic illness were 4.61, 4.65, 14.53 and 17.33 %,
      respectively. Note that NCDs are the principal reason behind the latter two
      situations (about 88 % and 85 % of cases, respectively). Looking into individual
      categories of NCDs we found that major contribution to headcount impoverishment
      arose out of illnesses such as cholecystectomy, mental disorder, kidney disease,
      cancer and appendectomy. The intensity of impoverishment is the largest among the
      hospitalized patients, and more individually among cancer patients. CONCLUSIONS:
      The poverty impact of OOP outlays for health care, in general, is quite high.
      However, it is especially high for NCDs, particularly for chronic NCDs and those
      requiring immediate surgical procedures. Hence, these illnesses should be given
      more priority for policy framing. In addition to suggesting some ex-ante measures
      (e.g. raising awareness regarding the risk factors causing NCDs), the paper
      argues for reforms to enhance efficiency in the public health care facilities and
      increasing the quality of public health care.

PMID- 24854551
TI  - Fast determination of ginsenosides in ginseng by high-performance liquid
      chromatography with chemometric resolution.
AB  - Ginseng is a well-known traditional Chinese medicinal herb, and ginsenosides are
      its major active components. A method for the fast determination of ginsenosides
      in ginseng samples by high-performance liquid chromatography was developed and
      used for the quantitative analysis of four ginsenosides in three different
      ginseng samples. In this method, instead of time-consuming gradient elution,
      isocratic elution was used to speed up the analysis. Under strong isocratic
      elution, all the ginsenosides are eluted in 2.3 min. Although the measured signal
      is composed of overlapped peaks with the interferences and background, the signal
      of ginsenosides can be extracted by chemometric resolution. A non-negative immune
      algorithm was employed to obtain the chromatographic information of the target
      components from the data. Compared with conventional chemometric approaches, the
      method can perform the extraction for one-dimensional overlapping signals. The
      method was validated by the determination of four ginsenosides in three different
      ginseng samples. The recoveries of the spiked samples were in the range of 94.08
      107.3%. 

PMID- 24854547
TI  - In vitro toxic effects of puff adder (Bitis arietans) venom, and their
      neutralization by antivenom.
AB  - This study investigated the in vitro toxic effects of Bitis arietans venom and
      the ability of antivenom produced by the South African Institute of Medical
      Research (SAIMR) to neutralize these effects. The venom (50 ug/mL) reduced nerve
      mediated twitches of the chick biventer muscle to 19% +/- 2% of initial magnitude
      (n = 4) within 2 h. This inhibitory effect of the venom was significantly
      attenuated by prior incubation of tissues with SAIMR antivenom (0.864 ug/uL; 67%
      +/- 4%; P < 0.05; n = 3-5, unpaired t-test). Addition of antivenom at t50 failed
      to prevent further inhibition or reverse the inhibition of twitches and responses
      to agonists. The myotoxic action of the venom (50 ug/mL) was evidenced by a
      decrease in direct twitches (30% +/- 6% of the initial twitch magnitude) and
      increase in baseline tension (by 0.7 +/- 0.3 g within 3 h) of the chick biventer.
      Antivenom failed to block these effects. Antivenom however prevented the venom
      induced cytotoxic effects on L6 skeletal muscle cells. Venom induced a marginal
      but significant reduction in plasma clotting times at concentrations above 7.8
      ug/100 uL of plasma, indicating poor procoagulant effects. In addition, the
      results of western immunoblotting indicate strong immunoreactivity with venom
      proteins, thus warranting further detailed studies on the neutralization of the
      effects of individual venom toxins by antivenom. 

PMID- 24854552
TI  - [Expression and significance of IKBKB in pulmonary adenocarcinoma A549 cells and
      its cisplatin-resistant variant A549/DDP].
AB  - BACKGROUND AND OBJECTIVE: Cisplatin-resistance in Lung cancer cells is widespread
      in the clinical treatment, seriously affecting the effects of the treatment of
      lung cancer. Therefore, the research of mechanisms of cisplain-resistance has
      significant meaning for developing new chemotherapeutic drug and solving the
      cisplain-resistance in clinic treatment. IKBKB is one of the most important
      catalytic subunits of IKK complexes. It plays an important regulatory role in
      activation of NF-kappaB. The aim of this study is to investigate the differential
      expression of IKBKB gene in human lung adenocarcinoma cells line A549 and the
      cisplatin-resistant variant A549/DDP and the mechanisms of cisplain-resistance
      induced by IKBKB gene. METHODS: MTT assay was employed to determine the
      sensitivity of A549 and A549/DDP cells line to cisplatin and the effect of IKBKB
      gene on A549 cell lines' sensitivity to cisplatin. The mRNA level of IKBKB was
      determined by real-time PCR. Dual luciferase reporter gene experiment was
      employed to determine the activity of the NF-kappaB. Apoptosis rate of lung
      adenocarcinoma cells was determined by flow cytometry. RESULTS: Apoptosis rate
      and IC50 were significantly different in A549 and A549/DDP cells, the expression
      of mRNA level of IKBKB gene in A549/DDP was significantly higher than that in
      A549. Compared with control group, IKBKB gene was able to reduce the cisplain
      sensitivity of A549 cells. After A549 was transfected with pcDNA3.1/IKBKB
      plasmid, mRNA level of IKBKB was significantly increased, the sensitivity of
      cisplain was decreased, the IC50 was increased 2.85 fold, the apoptosis rate was
      decreased 59%, the activity of NF-kappaB has been greatly increased. CONCLUSIONS:
      IKBKB inhibits cisplatin-induced apoptosis via the activation of NF-kappaB
      pathway. It will be helpful in the development of new anticancer drug and solving
      the challenge of cisplatin-resistance.

PMID- 24854553
TI  - [Construction and influence of human nuclear factor-kappaB p65 shRNA lentiviral
      ?vector on malignant biological behavior of lung cancer cells].
AB  - BACKGROUND AND OBJECTIVE: Nuclear factor-kappaB is an important transcription
      factor and is closely associated with a variety of malignant tumors. The
      biological behavior of lung tumor cells can be reversed by inhibiting the
      expression of NF-kappaBp65 directly or indirectly. Nuclear factor-kappaBp65 gene
      shRNA recombinant plasmids were constructed and then infected with A549 cells.
      New stable cell lines were selected, and the ability of migration and adhesion
      was identified. METHODS: Both scramble control sequence and interference sequence
      (shRNA) of human nuclear factor-kappaBp65 were designed and synthesized to build
      recombinant plasmids, with BamH I site at the 5' end and Xho I and EcoR I sites
      at the 3' end. A549 cells were infected, and stable transfection strains were
      selected by puromycin. Western blot and qRT-PCR methods were applied to assess
      the interference efficient of NF-kappaBp65 and the protein expression level of
      IkappaBalpha. Transwell and MTT assays were carried out to analyze the ability of
      migration and adhesion of A549 cells separately. RESULTS: Recombinant plasmids
      were successfully built, and A549/NF-kappaB p65 scramble and A549/NF-kappaB p65
      shRNA stable transfection strains were also successfully screened. Both mRNA and
      protein expression levels of NF-kappaBp65 showed that A549/NF-kappaBp65 shRNA
      cells decreased compared with A549/NF-kappaB p65 scramble cells and A549 cells,
      whereas the protein level of IkappaBalpha significantly increased. Both migration
      and adhesion abilities were also reduced. CONCLUSIONS: In this study, both mRNA
      and protein expression levels of NF-kappaBp65 were effectively suppressed by RNA
      interference technique. NF-kappaBp65 inhibition can significantly reduce the
      migration and adhesion ability of A549 cells.

PMID- 24854554
TI  - [Thymosin beta 10 prompted the VEGF-C expression in lung cancer cell].
AB  - BACKGROUND AND OBJECTIVE: Our previous study found that thymosin beta10
      overexpressed in lung cancer and positively correlated with differentiation,
      lymph node metastasis and stage of lung cancer. In this reasearch we aim to study
      the effects and mechanism of exogenous human recombinant Tbeta10 on the
      expression of VEGF-C on non-small cell lung cancer. METHODS: After SPC, A549 and
      LK2 cells were treated with 100 ng/mL recombinant human Tbeta10, the mRNA level
      of VEGF-C were detected by RT-PCR. The mean while the protein expression of VEGF
      C, P-AKT and AKT were determined by Western blot assay. RESULTS: Exogenous
      recombinant human Tbeta10 were significantly promote the expression levels of
      VEGF-C mRNA and protein while promoting the phosphorylation of AKT. Exogenous
      Tbeta10 can promote the expression of VEGF-C mRNA and protein in lung cancer cell
      lines A549 and LK2 (P<0.05), and this effect can be inhibited by use AKT
      inhibitor LY294002 (P<0.05). CONCLUSIONS: Tbeta10 human recombinant proteins can
      promote the expression of VEGF-C by activating AKT phosphorylation in lung cancer
      cell lines.

PMID- 24854555
TI  - [MiR-192 confers cisplatin resistance by targeting Bim in lung cancer].
AB  - BACKGROUND AND OBJECTIVE: Cisplatin is the first-line drug for the chemotherapy
      of non-small cell lung cancer (NSCLC), but the acquired chemoresistance
      restricted the effect of its treatment. The aim of this study is to validate the
      miRNAs related to the Cisplatin resistance in lung cancer and elucidate the
      molecular mechanisms. METHODS: We performed miRNA microarray and RT-PCR to obtain
      the aberrant differential expressed miRNAs between A549 and its paired Cisplatin
      resistant cell line A549/DDP cells, and then we investigated the biological
      functions of miR-192, which is the aberrant differential expressed miRNA. After
      transfection of the miR-192 into A549 cells, we measured the half inhibition
      concentration (IC50), cell apoptosis of the trasfectant cells, and then we used
      biological softwares and dual-luciferase report assay to explore the target gene
      of the miR-192, which was further validated by RT-PCR and Western blot. RESULTS:
      MiR-192 was highly over-expressed in A549/DDP cells , whose quantity was 37.59+/
      0.35 fold higher than that in A549 cells. Overexpression of miR-192 in A549 cells
      significantly conferred resistance to Cisplatin and inhibited apoptosis. By
      contrast, down-expression of miR-192 in A549/DDP cells remarkably restrained the
      Cisplatin resistance and induced apoptosis. MiR-192 binded to Bim 3'-UTR and
      negatively regulated Bim expression at the post-transcriptional level in lung
      adenocarcinoma cells. CONCLUSIONS: Our data suggested that miR-192 induced
      Cisplatin-resistance and inhibited cell apoptosis in lung cancer via negative
      targeting Bim expression.

PMID- 24854556
TI  - [Joint serum tumor markers serve as survival predictive model of erlotinib in the
      treatment of recurrent non-small cell lung cancer].
AB  - BACKGROUND AND OBJECTIVE: Molecular targeting therapy is the direction of
      individualized treatment of lung cancer, scholars has been established targeted
      therapy prediction models which provide more guidance for clinical individual
      therapy. This study investigated the relationship among pulmonary surfactant
      associated protein D (SP-D), transforming growth factor alpha (TGF-alpha), matrix
      metalloproteinase 9 (MMP-9), tissue polypeptide specific antigen (TPS), and Krebs
      von den Lungen-6 (KL-6) and response as well as survival in the patients with
      recurrent non-small cell lung cancer, which Erlotinib was as second line
      treatment after failure to chemotherapy. This study also established a predictive
      prognostic model. METHODS: Serum levels of SP-D, TGF-alpha, MMP-9, TPS, and KL-6
      in 114 patients before erlotinib treatment were detected by ELISA method.
      Combined with clinical factors, these levels were used to investigate the
      relationship with efficacy in erlotinib treatment and construct a predicted
      prognostic model by Kaplan-Meier curve and Cox proportional hazard model
      multivariate analysis. RESULTS: The objective response rate (ORR) and disease
      control rate (DCR) in the 114 patients, were 22.8% (26/114) and 72.8% (83/114),
      to Erlotinib treatment respectively. The median progression-free survival (PFS)
      and one year survival rate with Erlotinib treatment were 5.13 months and 69.3%,
      respectively. Patients in the SP-D>110 ng/mL group exhibited more ORR (33.3% vs
      13.3%, P=0.011) and DCR (83.3% vs 63.3%, P=0.017) than those in the <=110 ng/mL
      group. Patients in the MMP-9<=535 ng/mL group showed more DCR (83.9%) than those
      in the >535 ng/mL group (62.1%) (P=0.009). Patients in the TPS<80 U/L group
      showed more DCR (82.4%) than those in the >=80 U/L group (55.0%) (P=0.002). The
      SP-D>110 ng/mL (5.95 months vs 3.25 months, P=0.009), MMP-9<=535 ng/mL (5.83
      months vs 3.47 months, P=0.046), KL-6<500 U/mL (6.03 months vs 3.40 months,
      P=0.040), and TPS<80 U/L (6.15 months vs 2.42 months, P=0.014) groups showed
      better PFS. Multivariate analysis showed that current or ever-smoker, wild style
      of EGFR status, progression after prior chemotherapy, absence of skin rash,
      elevated serum LDH level, and TPS>=80 U/L were independent adverse prognostic
      factors for PFS. These six factors were used in the prognostic model. Patients
      were categorized into four prognosis risk groups based on the prognostic index
      from the model, namely, low risk, intermediate low risk, intermediate risk, and
      high risk groups. The median PFS of good, intermediate, poor, and very poor
      prognosis groups were 9.12, 6.88, 3.52, and 0.93 months (P<0.001), respectively.
      CONCLUSIONS: The prognostic model based on clinical parameters with TPS will be
      useful in identifying patients who might be most likely to benefit from Erlotinib
      therapy in the patients with recurrent non-small cell lung cancer.

PMID- 24854558
TI  - [MSCT imaging diagnosis of peripheral lung cancer with dry pleural
      dissemination].
AB  - BACKGROUND AND OBJECTIVE: The rate of pleural metastasis in peripheral lung
      cancer is high, and the dry pleural metastasis easily missed diagnosis
      preoperatively and cause unnecessary surgery. Therefore, preoperative diagnosis
      is particularly important. To review the multislice spiral computed tomography
      (MSCT) image of peripheral lung cancer with dry pleural dissemination, and to
      discuss its diagnostic value for understanding the dry pleural dissemination.
      METHODS: Reviewed and analyzed the MSCT images of pathologically or clinically
      diagnosed peripheral lung cancer with dry pleural dissemination in 27 patients.
      Analyze the imaging characteristics respectively from pleural thickening and
      pleural nodules. RESULTS: The dry pleural dissemination of lung cancer were
      detected in 85% by CT. The rate of CT detection of dissemination on the visceral
      pleura and the interlobar pleura were 63% and 91%, respectively. 26 cases were
      with multiple pleural nodules, all were located on the same side with the primary
      lesions; 8 cases were with peritoneum visceralis nodules that are mostly circular
      with diameters of 3 mm-15 mm. The lung-nodules interfaces were clear. 23 cases
      had interlobar pleura nodules (all with more than 6 nodules), some are big
      (diameter >5 mm) while some are small (diameter <5 mm). The nodules are arranged
      along the interlobar pleura as beaded string or in clusters around the interlobar
      pleura. 15 cases were with pleural thickening, including band-like, uneven, or
      both exist at the same time. There are more mixed type in this group (63%).
      CONCLUSIONS: MSCT has great diagnostic value for peripheral lung cancer with dry
      pleural dissemination, especially with high accuracy of pleural nodules.

PMID- 24854557
TI  - [Efficacy of gefitinib for young patients with unknown EGFR gene mutation ?in
      advanced lung adenocarcinoma].
AB  - BACKGROUND AND OBJECTIVE: Lung cancer in young patients (less or equal to 45
      years) is relatively rare. We explored the efficacy and survival of Gefitinib for
      young patients with unknown epidermal growth factor receptor (EGFR) gene mutation
      of advanced lung adenocarcinoma. METHODS: The clinical data of 55 young patients
      with unknown EGFR gene mutation in advanced lung adenocarcinoma referred to the
      Cancer Hospital & Institute, Chinese Academy of Medical Sciences from Jan 2006
      through Dec 2010 were analyzed retrospectively. RESULTS: Of 55 young patients
      enrolled, the median age was 41 years. The objective response rate and disease
      control rate were 43.6% and 90.9%, respectively.. The median progression-free
      survival (PFS) was 9.0 months. Among the factors analyzed, brain metastasis had
      significant effect on PFS (P=0.017). The median overall survival (OS) was 24.0
      months. The independent prognostic factors to significantly improve OS included
      non-smoking history (P=0.028) and receiving other anti-cancer treatment after
      Gefitinib therapy (P<0.001). CONCLUSIONS: The median PFS and OS of the young
      patients with Unknown EGFR gene mutation in advanced lung adenocarcinoma were
      similar with general population.

PMID- 24854559
TI  - [High risk indication of postoperative chemotherapy ?in early stage non-small
      cell lung cancer].
AB  - BACKGROUND AND OBJECTIVE: More than 35% Ib stage lung cancers have metastasised
      or recurrenced after operation, whose prognosis still remain poor. There're much
      controversy over the necessity of adjuvant chemotherapy to them. This aim of this
      study is investigated the clinical and pathological characters influencing
      prognosis of the stage Ib non-small cell lung cancer (NSCLC) and to explore the
      indication of postoperative chemotherapy. METHODS: NSCLC patients (281 cases) who
      underwent lobectomy were examined. Cox proportional-hazards ratios were used to
      identify independent prognostic factors for survival. Kaplan-Meier survival
      curves were calculated to estimate survival rates. RESULTS: Kaplan-Meier analysis
      show that, cancerous embolus in the blood vessel or lymphatic vessel, histologic
      grade and tumor location were remarkerbly associated with mortality risk
      (P<0.05). The poor histologic grade and cancerous embolus in the blood vessel
      were closely associated with increased mortality risk on multivariate analysis in
      stage Ib NSCLC. CONCLUSIONS: The low histologic grade and cancerous embolus in
      the blood vessel or lymphatic vessel are closely correlated with survival in the
      stage Ib NSCLC and can be an index for the postoperative chemotherapy.

PMID- 24854560
TI  - [Association of MiR-155 expression with prognosis in resected ?stage III non
      small cell lung cancer].
AB  - BACKGROUND AND OBJECTIVE: Despite undergoing curative resection, the 5-year
      survival rate for stage III non-small cell lung cancer (NSCLC) patients is less
      than 25%. There is a need for biomarkers for prediction of survival and guiding
      individual therapy. MiR-155 is one of most commonly upregulated miRNAs in
      malignancies, and regulates multiple pro-oncogenic pathways. We aimed to
      investigate the prognostic impact of miR-155 in resected stage III NSCLC
      patients. METHODS: Tumor formalin-fixed, paraffin-embedded (FFPE) from 162
      resected stage III NSCLC patients were collected. Total RNA including miRNA was
      extracted, and qRT-PCR was used to determine the expression of miR-155. RESULTS:
      Spearman rank correlation test showed a positive correlation between miR-155
      expression and nodal status (r=0.169, P=0.032). MiR-155 expression had a
      significant prognostic impact in the total cohort (P<0.001), in squamous cell
      carcinomas (P=0.002) and in adenocarcinomas (P=0.003). In N0-1 subgroup, miR-155
      expression did not have a significant prognostic on overall survival in
      univariate analysis (P=0.319). In N2 subgroup, miR-155 had a negative prognostic
      effect on OS in univariate analysis (P<0.001). Cox regression analysis revealed
      that miR-155 expression was unfavorable prognostic factors of OS (RR=2.311,
      95%CI: 1.479-3.611, P<0.001). CONCLUSIONS: High expression of miR-155 represents
      a valuable marker of poor clinical outcomes in patients with stage III NSCLC.

PMID- 24854561
TI  - [Analysis of single-operation-hole thoracoscopic lobectomy in 113 clinical
      cases].
AB  - BACKGROUND AND OBJECTIVE: Video-assisted thoracoscopic surgery (VATS) lobectomy
      is generally accepted for patients with lung cancer. The aim of this study is to
      explore the feasibility of the single-operation-hole thoracoscopic lobectomy in
      the treatment of non-small cell lung cancer. METHODS: To review and analyze the
      single-operation-hole thoracoscopic lobectomy performed in our hospital for 113
      non-small cell lung cancer (NSCLC) cases from October 2010 to October 2013. The
      incision for observation was 1.5 cm the eighth intercostal at the rear of the
      midaxillary line and the incision for operation was 2.0 cm-4.0 cm at the fourth
      or fifth intercostal of the anterior axillary line. The operations were performed
      through the single-operation-hole. RESULTS: The operation processes were smooth
      for all the patients without any operative mortality occurrence. Only in 5 cases
      was the operation hole expanded because of the occurrence of massive hemorrhage
      during the operation; 3 patients with postoperative complications underwent
      thoracoscopic lobectomy again, including 2 cases of delayed hemorrhage and 1 case
      of chylothorax. The average surgical duration was (178.24+/-31.17) min, the
      average blood loss was (213.56+/-62.38) mL, and the number of lymph nodes
      dissected was from 5-22. All diagnose were confirmed by pathology after
      operation. The average length of stay was (8.17+/-2.93) d. All cases recovered
      well during the follow-up of (2-38) months, only 5 cases had recurrence or
      metastasis. CONCLUSIONS: The single-operation-hole thomcoscopic lobectomy for
      lung cancer is safe and feasible, further reducing the trauma, and can be used as
      a conventional treatment for early- or medium-term NSCLC.

PMID- 24854562
TI  - [Current translational research status of ERCC1 expression of ?non-small cell
      lung cancer].

PMID- 24854563
TI  - [Advances on driver oncogenes of squamous cell lung cancer].
AB  - BACKGROUND AND OBJECTIVE: Lung cancer is the leading cause of cancer-related
      deaths worldwide. Next to adenocarcinoma, squamous cell carcinoma (SCC) of the
      lung is the most frequent histologic subtype in non-small cell lung cancer.
      Several molecular alterations have been defined as "driver oncogenes" responsible
      for both the initiation and maintenance of the malignancy. The squamous cell
      carcinoma of the lung has recently shown peculiar molecular characteristics which
      relate with both carcinogenesis and response to targeted drugs. So far, about 40%
      of lung squamous cell carcinoma has been found harbouring driver oncogenes, in
      which fibroblast growth factor receptor 1 (FGFR1) plays important roles. In this
      review, we will report the mainly advances on some latest driver mutations of
      squamous cell lung cancer.

PMID- 24854564
TI  - Health outcomes for children with neurodisability: what do professionals regard
      as primary targets?
AB  - AIM: To identify what aspects of health clinicians target when working with
      children with neurodisability, and which might be appropriate to assess the
      performance of health services. METHOD: Health professionals were recruited
      through child development teams and professional societies in England.
      Professionals participated in four rounds of an online Delphi survey. Open
      questions were used to elicit aspects of health; these were coded using the WHO
      International Classification of Functioning, Disability and Health for Children
      and Youth. Then, participants were asked to rate their agreement with statements
      to prioritise outcomes identified. RESULTS: Responses to all four rounds were,
      respectively: 233/276 (84.4%), 232/286 (81.1%), 227/285 (79.6%) and 191/284
      (67.3%). The key outcome domains identified were: mental health,
      confidence/emotional stability, anxiety/attention, sleep, pain, toileting,
      movement ability, manual ability, acquiring skills, communication, mobility, self
      care, recreation and leisure. Participants rated both functioning and well-being
      in these aspects of health as equally important. INTERPRETATION: This Delphi
      survey identified nine key domains that provide a professional perspective on a
      core set of outcomes for evaluating services for children and young people with
      neurodisability.

PMID- 24854565
TI  - Role of preferential cyclooxygenase-2 inhibition by meloxicam in
      ischemia/reperfusion injury of the rat liver.
AB  - BACKGROUND: Ischemia/reperfusion injury (IRI) is one of the major clinical
      problems in liver and transplant surgery. Livers subjected to warm ischemia in
      vivo often show a severe dysfunction and the release of numerous inflammatory
      cytokines and arachidonic acid metabolites. Cyclooxygenase (COX)-2 is the
      inducible isoform of an intracellular enzyme that converts arachidonic acid into
      prostaglandins. The aim of the study was to evaluate the effect of COX-2
      inhibition and the role of Kupffer cells in IRI of the liver. METHODS: Male
      Wistar rats [250- 280 g body weight (BW)] were anesthetized and subjected to 30
      min warm ischemia of the liver (Pringle's maneuver) and 60-min reperfusion after
      median laparotomy. The I/R group received no additional treatment. In the COX-2
      inhibitor (COX-2I) group, the animals received 1 mg/kg BW meloxicam prior to
      operation. Gadolinium chloride (GdCl3) (10 mg/kg BW) was given 24 h prior to
      operation in the GdCl3 and GdCl3 + COX-2I groups for the selective depletion of
      Kupffer cells. The GdCl3 + COX-2I group received both GdCl3 and meloxicam
      treatment prior to operation. Blood and liver samples were obtained at the end of
      the experiments for further investigations. RESULTS: After 30 min of warm
      ischemia in vivo, severe hepatocellular damage was observed in the I/R group.
      These impairments could be significantly prevented by the selective COX-2
      inhibition and the depletion of Kupffer cells. Alanine aminotransferase was
      significantly reduced upon meloxicam and GdCl3 treatment compared to the I/R
      group: I/R, 3,240 +/- 1,262 U/l versus COX-2I, 973 +/- 649 U/l, p < 0.001; I/R
      versus GdCl3, 1,611 +/- 600 U/l, p < 0.05, and I/R versus GdCl3 + COX-2I, 1,511
      +/- 575 U/l, p < 0.01. Plasma levels of tumor necrosis factor alpha (TNF-alpha)
      were significantly reduced in the COX-2I treatment group compared to I/R (3.5 +/-
      1.5 vs. 16.3 +/- 11.7 pg/ml, respectively; p < 0.05). Similarly, the amount of
      TxB2, a marker for COX-2 metabolism, was significantly reduced in the meloxicam
      treatment groups compared to the I/R group: I/R, 22,500 +/- 5,210 pg/ml versus
      COX-2I, 1,822 +/- 938 pg/ml, p < 0.001, and I/R versus GdCl3 + COX-2I, 1,530 +/-
      907 pg/ml, p < 0.001. All values are given as mean +/- SD (n = 6). CONCLUSION:
      These results suggest that the inhibition of COX-2 suppressed the initiation of
      an inflammatory cascade by attenuating the release of TNF-alpha, which is an
      initiator of the inflammatory reaction in hepatic IRI. Therefore, we conclude
      that preferential inhibition of COX-2 is a possible therapeutic approach against
      warm IRI of the liver.

PMID- 24854566
TI  - Dose conversion factor between cyclosporine and tacrolimus in pediatric heart
      transplant recipients.

PMID- 24854567
TI  - Emotional symptoms and quality of life in patients with pulmonary arterial
      hypertension.
AB  - BACKGROUND: Limited evidence exists on the nature and degree of emotional
      problems in pulmonary arterial hypertension (PAH) and their association with
      patients' health-related quality of life (HRQOL). METHODS: This cross-sectional
      study examined the presence of depression, anxiety, and stress symptoms, and
      their association with disease-specific and generic HRQOL. A total of 101
      patients (73% women) with PAH (age, 55.4 +/- 16.4 years; 42.6% in New York Heart
      Association [NYHA] class II) completed the Depression, Anxiety, and Stress Scale,
      the generic Medical Outcomes Study Short-Form 36-Item (SF-36) Health Survey, and
      the disease-specific Minnesota Living With Heart Failure Questionnaire (MLHFQ)
      HRQOL instrument. The association between emotional problems and HRQOL was
      determined using multivariable linear regression analyses, controlling for
      demographic and disease-related characteristics. RESULTS: Of the patients, 32.6%,
      48%, and 27.6% experienced depressive, anxiety or stress symptoms, respectively.
      HRQOL was >1 standard deviation below population norms for the SF-36 Physical
      Component Summary. Depressive symptoms, NYHA class, and being disabled explained
      46% of the total variance of the MLHFQ. Emotional problems did not contribute to
      the SF-36 Physical Component Summary but explained part of the variance of the
      physical sub-scales of the SF-36 role limitations due to physical problems,
      bodily pain, and general health. CONCLUSIONS: The high presence of emotional
      problems warrants regular screening and appropriate psychotherapeutic and/or
      pharmacological treatment. Which strategies could improve PAH patients' HRQOL
      remains to be investigated.

PMID- 24854568
TI  - Crystal structure of the secreted protein HP1454 from the human pathogen
      Helicobacter pylori.
AB  - HP1454 is a protein of 303 amino acids found in the extracellular milieu of
      Helicobacter pylori. The protein structure, crystallized in the orthorhombic
      C2221 space group with one molecule per asymmetric unit, has been determined
      using the single-wavelength anomalous dispersion method. HP1454 exhibits an
      elongated bent shape, composed of three distinct domains. Each domain possesses a
      fold already present in other structures: Domain I contains a three-strand
      antiparallel beta-barrel flanked by a long alpha-helix, Domain II is an anti
      parallel three-helix bundle, and Domain III a beta-sheet flanked by two alpha
      helices. The overall assembly of the protein does not bear any similarity with
      known structures.

PMID- 24854569
TI  - Antinociceptive activity of the HPLC- and MS-standardized hydroethanolic extract
      of Pterodon emarginatus Vogel leaves.
AB  - Several studies have demonstrated the analgesic and anti-inflammatory effects of
      fruit and seed extracts from Pterodon emarginatus Vogel (Fabaceae). The objective
      of this study was to evaluate the antinociceptive activity of the hydroethanolic
      extract of P. emarginatus leaves in mice and characterize its chemical
      composition using HPLC coupled to UV-vis diode array detection and mass
      spectrometry with electrospray ionization. Our results showed that the doses of
      500 and 1000 mg/kg produced an antinociceptive effect, as observed in the hot
      plate test and writhing induced by acetic acid. The chromatographic profile and
      spectral mass data suggest the presence of di-C-glycosylflavones (e.g., vicenin-2
      and schaftoside), C,O-glycosylflavones (e.g., chrysoeriol-8-C-glucosyl-2"-O
      glucuronide-6-C-arabinoside) and luteolin-7-O-rutinoside as the main
      constituents. Lower levels of oleanane-type saponins, such as soyasaponin Bb and
      Be, and the saponin derivatives hederagenin and aglycone B, which are typical of
      Fabaceae family, were also found. From this study, it is suggested that the
      analgesic effect observed is not due to the terpenoids previously reported from
      fruit and seed extracts, but could be attributed to flavones and the hederagenin
      derivatives that were identified as main constituents of the hydroethanolic
      extract from the leaves.

PMID- 24854570
TI  - Propolis cinnamic acid derivatives induce apoptosis through both extrinsic and
      intrinsic apoptosis signaling pathways and modulate of miRNA expression.
AB  - Propolis cinnamic acid derivatives have a number of biological activities
      including anti-oxidant and anti-cancer ones. In this study, we aimed to elucidate
      the mechanism of the anti-cancer activity of 3 representative propolis cinnamic
      acid derivatives, i.e., Artepilin C, Baccharin and Drupanin in human colon cancer
      cell lines. Our study demonstrated that these compounds had a potent apoptosis
      inductive effect even on drug-resistant colon cancer cells. Combination treatment
      of human colon cancer DLD-1 cells with 2 of these compounds, each at its IC20
      concentration, induced apoptosis by stimulating both intrinsic and extrinsic
      apoptosis signaling pathways. Especially, Baccharin plus Drupanin exhibited a
      synergistic growth-inhibitory effect by strengthening both intrinsic and
      extrinsic apoptotic signaling transduction through TRAIL/DR4/5 and/or FasL/Fas
      death-signaling loops and by increasing the expression level of miR-143,
      resulting in decreased expression levels of the target gene MAPK/Erk5 and its
      downstream target c-Myc. These data suggest that the supplemental intake of these
      compounds found in propolis has enormous significance with respect to cancer
      prevention. 

PMID- 24854571
TI  - Puerarin concurrently stimulates osteoprotegerin and inhibits receptor activator
      of NF-kappaB ligand (RANKL) and interleukin-6 production in human osteoblastic MG
      63 cells.
AB  - Puerarin, a daidzein-8-C-glucoside, is the major isoflavone glycoside found in
      the Chinese herb radix of Pueraria lobata (Willd.) Ohwi, and has received
      increasing attention because of its possible role in the prevention of
      osteoporosis. In our previous studies, puerarin reduced the bone resorption of
      osteoclasts and promoted long bone growth in fetal mouse in vitro. Further study
      confirmed that puerarin stimulated proliferation and differentiation of
      osteoblasts in rat. However, the mechanisms underlying its actions on human bone
      cells have remained largely unknown. Here we show that puerarin concurrently
      stimulates osteoprotegerin (OPG) and inhibits receptor activator of nuclear
      factor-kappaB ligand (RANKL) and Interleukin-6 (IL-6) production by human
      osteoblastic MG-63 cells containing two estrogen receptor (ER) isotypes.
      Treatment with the ER antagonist ICI 182,780 abrogates the above actions of
      puerarin on osteoblast-derived cells. Using small interfering double-stranded
      RNAs technology, we further demonstrate that the effects of puerarin on OPG and
      RANKL expression are mediated by both ERalpha and ERbeta but those on IL-6
      production primarily by ERalpha. Moreover, we demonstrate that puerarin may
      promote activation of the classic estrogen response element (ERE) pathway through
      increasing ERalpha, ERbeta and steroid hormone receptor coactivator (SRC)-1
      expression. Therefore, puerarin will be a promising agent that prevents or
      retards osteoporosis. 

PMID- 24854573
TI  - Peimisine and peiminine production by endophytic fungus Fusarium sp. isolated
      from Fritillaria unibracteata var. wabensis.
AB  - Steroidal alkaloids, as the major biologically active components in Bulbus
      Fritillariae, possess a variety of toxicological and pharmacological effects on
      humans. The objective of this work was to determine whether endophytic fungi
      isolated from fresh bulbs of Fritillaria unibracteata var. wabensis can produce
      one or more alkaloids like its host plant. Four classical reagents including
      Wagner's, iodine-potassium iodide, Mayer's and improved Dragendorff's were used
      for primary screening. Then thin-layer chromatography (TLC) and high performance
      liquid chromatography-evaporative light scattering detection (HPLC-ELSD) were
      employed to identify the fermentation products of the selected strains. The
      results showed that extract from one stain (WBS007) has positive reactions in
      process of primary screening. A further TLC scan and HPLC-ELSD showed that strain
      WBS007 had two components with the same TLC relative front (Rf) value and HPLC
      retention time (RT) as authentic peimisine and peiminine. In addition, strain
      WBS007 was identified as Fusarium sp. based on phylogenetic analysis of ITS
      sequences. Thus, strain WBS007 produced the bioactive ingredient peimisine and
      peiminine, as does its host plant, and could be used for the production of
      peimisine and peiminine by fermentation. 

PMID- 24854572
TI  - Platycodon grandiflorum root-derived saponins attenuate atopic dermatitis-like
      skin lesions via suppression of NF-kappaB and STAT1 and activation of Nrf2/ARE
      mediated heme oxygenase-1.
AB  - PURPOSE: The consequences of precipitously rising allergic skin inflammation
      rates worldwide have accelerated the risk of atopic dermatitis (AD). Natural
      product-based agents with good efficacy and low risk of side effects offer
      promising prevention and treatment strategies for inflammation-related diseases.
      We have already reported that Platycodon grandiflorum root-derived saponins
      (Changkil saponins, CKS) have many pharmacological effects, including anti
      inflammatory and anti-allergic effects, but its influence on AD remains unclear.
      Therefore, we evaluated the inhibitory effect of CKS, mainly platycodin D, on AD
      like skin symptoms in mice and the possible mechanisms in cells. METHODS: Mice
      were sensitized and challenged with 2,4-dinitrochlorobenzene (DNCB). Four weeks
      after challenge, mice were treated with oral administration of CKS for 4 weeks.
      In addition, cells were used to evaluate the effect of CKS, mainly platycodin D,
      on the TARC expression regulated mechanism. RESULTS: CKS attenuated DNCB-induced
      dermatitis severity, serum levels of IgE and TARC, and mRNA expression of TARC,
      TNF-alpha, IFN-gamma, IL-4, IL-5, and IL-13 in mice. Histopathological
      examination showed reduced thickness of the epidermis/dermis and dermal
      infiltration of inflammatory cells and mast cells in the ears. Moreover, CKS and
      platycodin D inhibited TNF-alpha/IFN-gamma-induced TARC expression through the
      suppression of NF-kappaB and STAT1 and induction of Nrf2/ARE-mediated
      hemeoxygenase-1 (HO-1) expression in cells. CONCLUSION: We suggest that CKS and
      platycodin D inhibited the development of AD-like skin symptoms by regulating
      cytokine mediators and may be an effective alternative therapy for AD-like skin
      symptoms.

PMID- 24854575
TI  - Split vector systems for ultra-targeted gene delivery: a contrivance to achieve
      ethical assurance of somatic gene therapy in vivo.
AB  - Tightly controlled spatial localisation of therapeutic gene delivery is essential
      to maximize the benefits of somatic gene therapy in vivo and to reduce its
      undesired effects on the 'bystander' cell populations, most importantly germline
      cells. Indeed, complete ethical assurance of somatic gene therapy can only be
      achieved with ultra-targeted gene delivery, which excludes the risk of
      inadvertent germline gene transfer. Thus, it is desired to supplement existing
      strategies of physical focusing and biological (cell-specific) targeting of gene
      delivery with an additional principle for the rigid control over spread of gene
      transfer within the body. In this paper I advance the concept of 'combinatorial'
      targeting of therapeutic gene transfer in vivo. I hypothesize that it is possible
      to engineer complex gene delivery vector systems consisting of several
      components, each one of them capable of independent spread within the human body
      but incapable of independent facilitation of gene transfer. As the gene delivery
      augmented by such split vector systems would be reliant on the simultaneous
      availability of all the vector system components at a predetermined body site, it
      is envisaged that higher order reaction kinetics required for the assembly of the
      functional gene transfer configuration would sharpen spatial localisation of gene
      transfer via curtailing the blurring effect of the vector spread within the body.
      A particular implementation of such split vector system could be obtained through
      supplementing a viral therapeutic gene vector with a separate auxiliary vector
      carrying a non-integrative and non-replicative form of a gene (e.g., mRNA) coding
      for a cellular receptor of the therapeutic vector component. Gene-transfer
      enabling components of the vector system, which would be delivered separately
      from the vector component loaded with the therapeutic gene cargo, could also be
      cell-membrane-insertion-proficient receptors, elements of artificial
      transmembrane channels capable of nucleic acid transfer or, perhaps, factors
      modifying existing cellular transmembrane channels (e.g., gap-junctional
      hemichannels) to serve as conduits for gene entry. In general, there are four
      possibilities for gene transfer in vivo using a split vector system: (1)
      simultaneous delivery of a mixture of the vector components to the same body
      site; (2) sequential delivery of the vector components to the same body site; (3)
      simultaneous delivery of the vector components to separate body sites; (4)
      sequential delivery of the vector components to separate body sites. It is hoped
      that, once experimentally confirmed, the combinatorial principle for tight
      control over localisation of gene transfer could be the critical element in
      attaining complete assurance of gene non-delivery to germline cells in somatic
      gene therapy in vivo. 

PMID- 24854574
TI  - Applying theories and interventions from behavioral medicine to understand and
      reduce visual field variability in patients with vision loss.
AB  - Visual field (VF) test results are often unreliable in visually impaired
      patients, but continue to be a cornerstone of clinical trials and play a vital
      role in clinical decision making since they are the primary method to determine
      patients' functional vision loss or progression. Currently, patients are
      typically asked to perform VF tasks with minimal instruction or consideration of
      their psychological experience during the test. The gradual loss of vision due to
      retinal diseases, such as retinitis pigmentosa (RP), age-related macular
      degeneration (AMD), or glaucoma can contribute to the experience of negative
      psychosocial states, such as anxiety, stress, and depression, as well as
      diminished quality of life. We hypothesize that VF testing elicits test
      performance anxiety and perception of functional losses of vision, which induces
      distracting negative thoughts that result in increased VF test variability.
      Resources for processing and responding to vision-related information may be
      diverted from task-relevant VF stimuli to task-irrelevant ones, such as internal
      worry and test anxiety, thereby resulting in VF test performance decrements. We
      present a theoretical model to support the hypothesis that VF variability is
      linked to patients' negative thoughts during VF testing. This conceptual
      framework provides a basis for the development of coping strategies and
      mindfulness-based interventions to be evaluated in future research aimed at
      improving psychosocial states and VF reliability in visually-impaired patients.
      It would be highly significant to intervene by modifying negative thoughts during
      VF testing to reduce test variability in glaucoma patients who are progressively
      losing vision to a blinding eye disease, but whose vision loss has not been
      accurately identified and treated early enough due to variable VF results. In
      clinical trials of potential interventions for RP and non-neovascular AMD,
      reducing VF variability would effectively increase the precision for detecting
      treatment effects and allow a reduction in the number of VF tests needed to
      estimate the treatment responses, thus reducing burden on investigators and
      patients, as well as saving time and money. 

PMID- 24854577
TI  - Increasing rates of prenatal testing among Jewish and Arab women in Israel over
      one decade.
AB  - BACKGROUND/AIMS/OBJECTIVE: This study compared data on the use of prenatal tests
      offered to pregnant women in Israel as reported in a national survey conducted by
      the Israel Center for Disease Control in 2001 to data from 2010. METHODS: Mothers
      of newborns were interviewed 8-72 h after delivery in 29 maternity wards in
      Israel on May 31, 2010. RESULTS: A total of 768 women were interviewed, 569
      (72.3%) were Jewish and 197 (25.7%) were Arabs. Nuchal translucency screening and
      early ultrasound level 2 were significantly more frequently done in both Jewish
      and Arab women in 2010 than in 2001. The use of the biochemical triple marker
      test and amniocentesis did not change. The increased rate of nuchal translucency
      screening and early ultrasound level 2 was significantly higher among the Jewish
      women compared to the Arabs (21.5 and 28.0% vs. 2.9 and 13.7% in 2001; 62.0 and
      65.6% vs. 30.1 and 30.9% in 2010, respectively). The rates of amniocentesis in
      the Jewish women aged >=35 years were 47.6 and 47.5% in 2001 and 2010,
      respectively; they are significantly higher than among the Arabs (18.5 and 28.5%,
      respectively). The factors associated with making more use of different prenatal
      tests were: secularity, a higher income, and supplementary medical insurance for
      the Jewish women, and supplementary medical insurance and printed information on
      prenatal testing for the Arabs. CONCLUSIONS: The prenatal testing rates have
      risen over the last decade in both population groups, but there are still
      significant gaps. We suggest that public funding of additional prenatal tests may
      increase their use in both population groups.

PMID- 24854576
TI  - Challenging the present definition of "normal" vitamin D levels obtained by a
      single blood test. Can we develop a formula to predict vitamin D levels in the 4
      seasons from a single season's measure?
AB  - Publications on the health effects of vitamin D (25(OH) D) had almost triplicate
      in the last 10years, not only for its known "calcemic effects" (calcium,
      phosphor, PTH), but for the more recent findings on its "non-calcemic effects"
      (all-cause and cardiovascular mortality, and relation with certain types of
      cancer). Part of these publications deal with the definition of what is a
      "normal" circulating level of 25(OH) D that may distinguish between health and
      disease. The literature also deals with seasonal variations of vitamin D, showing
      levels that rise in summer and fall in winter and with DBP phenotypes and
      geographical location that affect seasonality of 25(OH) D measurements. Despite
      the knowledge of the existence of these phenomena many studies on vitamin D fail
      to acknowledge the time of the year the blood sample was extracted. Thus, when we
      compare results from different studies without defining the season that the
      samples were drawn, we compare incomparable figures. Furthermore, it is quite
      absurd to define "normal levels" as a static measure (over or under a certain
      value) using a single blood test when the value measured is known to change with
      seasons. Knowing that people have different vitamin D levels in different seasons
      of the year, we should ask ourselves which of these measurements should be used
      to define a "real" or "normal" level? Is it the lower one? Is there a "mean
      measure" that should be used for this matter? If yes, how do we obtain it? Do we
      have to make 4 seasonal measurements in each patient? Alternatively, might there
      be a possibility of developing a formula to help us obtain the mean from a single
      season's measure or one season's prediction from another season's measurement?
      And knowing that DBP phenotypes and geographical location affect seasonality of
      25(OH) D measurements; shouldn't we include this in the equation? In this article
      I will discuss the hypothetical existence of an Individual Mean Annual vitamin D
      level that I will call the "IMAD level" and a recovery formula "RF" that may be
      used to calculate this mean having one single measure (in any of the 4 seasons)
      and to predict any season's value from another season's measurement. IMAD levels
      should be obtained in the two main DBP phenotypes, taking into account the
      geographical location of the test. 

PMID- 24854578
TI  - A chi-square goodness-of-fit test for autoregressive logistic regression models
      with applications to patient screening.
AB  - We propose a chi-square goodness-of-fit test for autoregressive logistic
      regression models. General guidelines for a two-dimensional binning strategy are
      provided, which make use of two types of maximum likelihood parameter estimates.
      For smaller sample sizes, a bootstrap p-value procedure is discussed. Simulation
      studies indicate that the test procedure satisfactorily approximates the correct
      size and has good power for detecting model misspecification. In particular, the
      test is very good at detecting the need for an additional lag. An application to
      a dataset relating to screening patients for late-onset Alzheimer's disease is
      provided. 

PMID- 24854579
TI  - Detection of antiranibizumab antibodies among patients with exudative age-related
      macular degeneration.
AB  - PURPOSE: The aim of this study was to detect immune responses induced by
      intravitreal injection (IVT) of ranibizumab in patients with exudative age
      related macular degeneration (AMD) in real life conditions. METHODS: An ELISA
      protocol from blood samples, following 2 different steps, was used to detect
      antibodies directed against the variable regions of ranibizumab. RESULTS: Among
      91 patients included, 46 received more than 10 IVTs, 36 had received 10 IVTs or
      fewer, and 9 were treatment naive. Specific antiranibizumab immunoglobulins G
      were detected in 14/82 treated patients (17.1%). No immunization was detected
      among naive patients. For patients with 10 or fewer previous IVTs, immunization
      against ranibizumab was detected in 4/36 patients (11.1%) whereas immunization
      was observed in 10/46 patients (21.7%) with more IVTs (p = 0.20). CONCLUSIONS:
      Immunization against ranibizumab can be detected in 17% of treated patients.
      Further clinical studies are needed to investigate the relationship between
      specific immunization to anti-vascular endothelial growth factor antibodies and
      response or resistance to ranibizumab treatments.

PMID- 24854581
TI  - Biodiversity of NPQ.
AB  - In their natural environment plants and algae are exposed to rapidly changing
      light conditions and light intensities. Illumination with high light intensities
      has the potential to overexcite the photosynthetic pigments and the electron
      transport chain and thus induce the production of toxic reactive oxygen species
      (ROS). To prevent damage by the action of ROS, plants and algae have developed a
      multitude of photoprotection mechanisms. One of the most important protection
      mechanisms is the dissipation of excessive excitation energy as heat in the light
      harvesting complexes of the photosystems. This process requires a structural
      change of the photosynthetic antenna complexes that are normally optimized with
      regard to efficient light-harvesting. Enhanced heat dissipation in the antenna
      systems is accompanied by a strong quenching of the chlorophyll a fluorescence
      and has thus been termed non-photochemical quenching of chlorophyll a
      fluorescence, NPQ. The general importance of NPQ for the photoprotection of
      plants and algae is documented by its wide distribution in the plant kingdom. In
      the present review we will summarize the present day knowledge about NPQ in
      higher plants and different algal groups with a special focus on the molecular
      mechanisms that lead to the structural rearrangements of the antenna complexes
      and enhanced heat dissipation. We will present the newest models for NPQ in
      higher plants and diatoms and will compare the features of NPQ in different algae
      with those of NPQ in higher plants. In addition, we will briefly address
      evolutionary aspects of NPQ, i.e. how the requirements of NPQ have changed during
      the transition of plants from the aquatic habitat to the land environment. We
      will conclude with a presentation of open questions regarding the mechanistic
      basis of NPQ and suggestions for future experiments that may serve to obtain this
      missing information. 

PMID- 24854585
TI  - Autoimmunity: A breakthrough to explain sex bias?

PMID- 24854586
TI  - Infectious disease: Opposing effects of IL-10.

PMID- 24854587
TI  - Macrophages: Peritoneal population depends on GATA6.

PMID- 24854580
TI  - Mouse knockout models for HIV-1 restriction factors.
AB  - Infection of cells with human immunodeficiency virus 1 (HIV-1) is controlled by
      restriction factors, host proteins that counteract a variety of steps in the life
      cycle of this lentivirus. These include SAMHD1, APOBEC3G and tetherin, which
      block reverse transcription, hypermutate viral DNA and prevent progeny virus
      release, respectively. These and other HIV-1 restriction factors are conserved
      and have clear orthologues in the mouse. This review summarises studies in
      knockout mice lacking HIV-1 restriction factors. In vivo experiments in such
      animals have not only validated in vitro data obtained from cultured cells, but
      have also revealed new findings about the biology of these proteins. Indeed,
      genetic ablation of HIV-1 restriction factors in the mouse has provided evidence
      that restriction factors control retroviruses and other viruses in vivo and has
      led to new insights into the mechanisms by which these proteins counteract
      infection. For example, in vivo experiments in knockout mice demonstrate that
      virus control exerted by restriction factors can shape adaptive immune responses.
      Moreover, the availability of animals lacking restriction factors opens the
      possibility to study the function of these proteins in other contexts such as
      autoimmunity and cancer. Further in vivo studies of more recently identified HIV
      1 restriction factors in gene targeted mice are, therefore, justified. 

PMID- 24854588
TI  - Post-transcriptional regulation of gene expression in innate immunity.
AB  - Innate immune responses combat infectious microorganisms by inducing inflammatory
      responses, antimicrobial pathways and adaptive immunity. Multiple genes within
      each of these functional categories are coordinately and temporally regulated in
      response to distinct external stimuli. The substantial potential of these
      responses to drive pathological inflammation and tissue damage highlights the
      need for rigorous control of these responses. Although transcriptional control of
      inflammatory gene expression has been studied extensively, the importance of post
      transcriptional regulation of these processes is less well defined. In this
      Review, we discuss the regulatory mechanisms that occur at the level of mRNA
      splicing, mRNA polyadenylation, mRNA stability and protein translation, and that
      have instrumental roles in controlling both the magnitude and duration of the
      inflammatory response.

PMID- 24854589
TI  - Monocytes and macrophages: developmental pathways and tissue homeostasis.
AB  - Monocytes and macrophages have crucial and distinct roles in tissue homeostasis
      and immunity, but they also contribute to a broad spectrum of pathologies and are
      thus attractive therapeutic targets. Potential intervention strategies that aim
      to manipulate these cells will require an in-depth understanding of their origins
      and the mechanisms that ensure their homeostasis. Recent evidence shows that
      monocytes do not substantially contribute to most tissue macrophage populations
      in the steady state or during certain types of inflammation. Rather, most tissue
      macrophage populations in mice are derived from embryonic precursors, are seeded
      before birth and can maintain themselves in adults by self-renewal. In this
      Review, we discuss the evidence that has dramatically changed our understanding
      of monocyte and macrophage development, and the maintenance of these cells in the
      steady state.

PMID- 24854592
TI  - Application of ANS fluorescent probes to identify hydrophobic sites on the
      surface of DREAM.
AB  - DREAM (calsenilin or KChIP-3) is a calcium sensor involved in regulation of
      diverse physiological processes by interactions with multiple intracellular
      partners including DNA, Kv4 channels, and presenilin, however the detailed
      mechanism of the recognition of the intracellular partners remains unclear. To
      identify the surface hydrophobic surfaces on apo and Ca(2+)DREAM as a possible
      interaction sites for target proteins and/or specific regulators of DREAM
      function the binding interactions of 1,8-ANS and 2,6-ANS with DREAM were
      characterized by fluorescence and docking studies. Emission intensity of ANS
      DREAM complexes increases upon Ca(2+) association which is consistent with an
      overall decrease in surface polarity. The dissociation constants for ANS binding
      to apoDREAM and Ca(2+)DREAM were determined to be 195+/-20MUM and 62+/-4MUM,
      respectively. Fluorescence lifetime measurements indicate that two ANS molecules
      bind in two independent binding sites on DREAM monomer. One site is near the
      exiting helix of EF-4 and the second site is located in the hydrophobic crevice
      between EF-3 and EF-4. 1,8-ANS displacement studies using arachidonic acid
      demonstrate that the hydrophobic crevice between EF-3 and EF-4 serves as a
      binding site for fatty acids that modulate functional properties of Kv4
      channel:KChIP complexes. Thus, the C-terminal hydrophobic crevice may be involved
      in DREAM interactions with small hydrophobic ligands as well as other
      intracellular proteins. 

PMID- 24854590
TI  - The mycobiota: interactions between commensal fungi and the host immune system.
AB  - The body is host to a wide variety of microbial communities from which the immune
      system protects us and that are important for the normal development of the
      immune system and for the maintenance of healthy tissues and physiological
      processes. Investigators have mostly focused on the bacterial members of these
      communities, but fungi are increasingly being recognized to have a role in
      defining these communities and to interact with immune cells. In this Review, we
      discuss what is currently known about the makeup of fungal communities in the
      body and the features of the immune system that are particularly important for
      interacting with fungi at these sites.

PMID- 24854591
TI  - The origins and functions of dendritic cells and macrophages in the skin.
AB  - Immune cell populations in the skin are predominantly comprised of dendritic
      cells (DCs) and macrophages. A lack of consensus regarding how to define these
      cell types has hampered research in this area. In this Review, we focus on recent
      advances that, based on ontogeny and global gene-expression profiles, have
      succeeded in discriminating DCs from macrophages in the skin. We discuss how
      these studies have enabled researchers to revisit the origin, diversity and T
      cell-stimulatory properties of these cells, and have led to unifying principles
      that extend across tissues and species. By aligning the DC and macrophage subsets
      that are found in mouse skin with those that are present in human skin, these
      studies also provide crucial information for developing intradermal vaccines and
      for managing inflammatory skin conditions.

PMID- 24854594
TI  - Reply to the letter to the editor called: results expected in 5-ALA-guided
      resection of glioblastoma.

PMID- 24854595
TI  - Response to "Emergency presentation and socioeconomic status in colon cancer".

PMID- 24854593
TI  - Identification of miR-423 and miR-499 polymorphisms on affecting the risk of
      hepatocellular carcinoma in a large-scale population.
AB  - AIMS: MicroRNAs (miRNAs) regulate gene expression and act as tumor suppressors or
      enhancers in oncogenesis. Single-nucleotide polymorphisms (SNPs) in miRNAs could
      alter the processing or actions of mature miRNA. So far, the association of miR
      423 rs6505162 with cancers has not been explored, while the association of miR
      499 rs3746444 was only reported in small-sized samples of different types of
      populations. METHODS: To evaluate the association of miR-499 rs3746444 and miR
      423 rs6505162 with hepatocellular carcinoma (HCC), we performed a large-scale
      case-control study of 984 patients with HCC and 991 cancer-free controls.
      RESULTS: The risk of HCC was significantly higher with miR-499 rs3746444 TC+CC
      genotypes compared with those with the TT genotype (odds ratio [OR]=1.372, 95%
      confidence intervals [CI]=1.099-1.713, p=0.005), as was the risk of hepatitis B
      virus-related HCC (OR=1.437, 95% CI=1.128-1.831, p=0.003). Moreover, subjects
      with the TC+CC genotypes were more vulnerable to advanced HCC with larger tumor
      size (chi(2)=13.014, p=0.001) and/or higher total bilirubin (p=0.004), which
      suggested that a TT genotype or T allele might serve as a protective factor. miR
      423 rs6505162 had no effect on the risk of HCC. CONCLUSIONS: miR-499 rs3746444
      may contribute to the risk and prognosis of HCC, indicating that this SNP could
      be developed as a biomarker for HCC prediction.

PMID- 24854596
TI  - Feature selection using genetic algorithms for fetal heart rate analysis.
AB  - The fetal heart rate (FHR) is monitored on a paper strip (cardiotocogram) during
      labour to assess fetal health. If necessary, clinicians can intervene and assist
      with a prompt delivery of the baby. Data-driven computerized FHR analysis could
      help clinicians in the decision-making process. However, selecting the best
      computerized FHR features that relate to labour outcome is a pressing research
      problem. The objective of this study is to apply genetic algorithms (GA) as a
      feature selection method to select the best feature subset from 64 FHR features
      and to integrate these best features to recognize unfavourable FHR patterns. The
      GA was trained on 404 cases and tested on 106 cases (both balanced datasets)
      using three classifiers, respectively. Regularization methods and backward
      selection were used to optimize the GA. Reasonable classification performance is
      shown on the testing set for the best feature subset (Cohen's kappa values of
      0.45 to 0.49 using different classifiers). This is, to our knowledge, the first
      time that a feature selection method for FHR analysis has been developed on a
      database of this size. This study indicates that different FHR features, when
      integrated, can show good performance in predicting labour outcome. It also gives
      the importance of each feature, which will be a valuable reference point for
      further studies. 

PMID- 24854597
TI  - Characterization of soluble thrombomodulin levels in patients with stage 3-5
      chronic kidney disease.
AB  - OBJECTIVE: This study aims to test the serum levels of soluble thrombomodulin
      (TM) in patients with chronic kidney disease (CKD)3-5 and to assess their
      connection with the different stages and severity of disease. METHODS: Sixty
      seven patients with CKD are included, disease severity was evaluated accordingly
      to CKD staging and clinical data is collected. Nineteen healthy volunteers served
      as healthy controls. Serum soluble TM is analyzed by ELISA. RESULTS: The levels
      of soluble TM in all patients with CKD were significantly higher than those of
      healthy controls (p < 0.001). CKD5 patients showed higher serum levels of soluble
      TM, in comparison to CKD4 patients (p = 0.001), CKD3 patients (p < 0.001), and
      healthy controls (p < 0.001). The correlation analysis revealed significant
      correlation between serum soluble TM and disease severity (r = 0.714, p < 0.001).
      Serum soluble TM was found to be correlated with eGFR (r = -0.766; p < 0.001) and
      serum creatinine (r = 0.778, p < 0.001). CONCLUSION: Soluble TM concentrations
      significantly increase in the CKD patients and are associated with the severity
      of the disease. Soluble TM may play critical roles in the development of CKD, as
      a biomarker of endothelial cells damage, anticoagulation and anti-inflammation.

PMID- 24854598
TI  - Emerging therapies for Parkinson's disease: from bench to bedside.
AB  - The prevalence of Parkinson's disease (PD) increases with age and is projected to
      increase in parallel to the rising average age of the population. The disease can
      have significant health-related, social, and financial implications not only for
      the patient and the caregiver, but for the health care system as well. While the
      neuropathology of this neurodegenerative disorder is fairly well understood, its
      etiology remains a mystery, making it difficult to target therapy. The currently
      available drugs for treatment provide only symptomatic relief and do not control
      or prevent disease progression, and as a result patient compliance and
      satisfaction are low. Several emerging pharmacotherapies for PD are in different
      stages of clinical development. These therapies include adenosine A2A receptor
      antagonists, glutamate receptor antagonists, monoamine oxidase inhibitors, anti
      apoptotic agents, and antioxidants such as coenzyme Q10, N-acetyl cysteine, and
      edaravone. Other emerging non-pharmacotherapies include viral vector gene
      therapy, microRNAs, transglutaminases, RTP801, stem cells and glial derived
      neurotrophic factor (GDNF). In addition, surgical procedures including deep brain
      stimulation, pallidotomy, thalamotomy and gamma knife surgery have emerged as
      alternative interventions for advanced PD patients who have completely utilized
      standard treatments and still suffer from persistent motor fluctuations. While
      several of these therapies hold much promise in delaying the onset of the disease
      and slowing its progression, more pharmacotherapies and surgical interventions
      need to be investigated in different stages of PD. It is hoped that these
      emerging therapies and surgical procedures will strengthen our clinical
      armamentarium for improved treatment of PD. 

PMID- 24854599
TI  - Intrathecal delivery of protein therapeutics to the brain: a critical
      reassessment.
AB  - Disorders of the central nervous system (CNS), including stroke,
      neurodegenerative diseases, and brain tumors, are the world's leading causes of
      disability. Delivery of drugs to the CNS is complicated by the blood-brain
      barriers that protect the brain from the unregulated leakage and entry of
      substances, including proteins, from the blood. Yet proteins represent one of the
      most promising classes of therapeutics for the treatment of CNS diseases. Many
      strategies for overcoming these obstacles are in development, but the relatively
      straightforward approach of bypassing these barriers through direct intrathecal
      administration has been largely overlooked. Originally discounted because of its
      lack of usefulness for delivering small, lipid-soluble drugs to the brain, the
      intrathecal route has emerged as a useful, in some cases perhaps the ideal, route
      of administration for certain therapeutic protein and targeted disease
      combinations. Here, we review blood-brain barrier functions and cerebrospinal
      fluid dynamics and their relevance to drug delivery via the intrathecal route,
      discuss animal and human studies that have investigated intrathecal delivery of
      protein therapeutics, and outline several characteristics of protein therapeutics
      that can allow them to be successfully delivered intrathecally. 

PMID- 24854600
TI  - The making of the Journal: 'On devient bon'.

PMID- 24854601
TI  - Increased FADS2-derived n-6 PUFAs and reduced n-3 PUFAs in plasma of atopic
      dermatitis patients.
AB  - Fatty acid concentrations, in particular n-3 and n-6 polyunsaturated fatty acids
      (PUFAs), have been described to be dysregulated in atopic dermatitis (AD)
      patients. The role of genetic polymorphisms of fatty acid enzymes in AD is
      controversial. We determined in a Hungarian cohort of healthy volunteers (n = 20)
      and AD patients (n = 20) triglyceride-, sterol- and phospholipid-bound fatty
      acids in the plasma, mRNA expression of fatty acid desaturase 2 (FADS2) and
      stearoyl-coenzyme A desaturase 1 in peripheral blood mononuclear cells (PBMCs)
      and FADS2 concentrations in plasma. We observed higher levels of monounsaturated
      fatty acids, 16:1 versus 16:0 ratios in phospholipids, triglycerides and sterol
      esters in patients compared to healthy subjects. In addition higher levels of the
      FADS2-derived n-6 PUFAs gamma-linolenic acid and dihomo-gamma-linolenic acid were
      observed in PBMCs of patients as well as lower levels of n-3 PUFAs. We conclude
      that the increased expression of FADS2 in PBMCs, as a representative tissue
      accessible from human blood of AD patients, might be responsible for higher
      levels of FADS2-derived n-6 PUFAs and lower n-3 PUFA levels in patients.

PMID- 24854602
TI  - Electrochemical monitoring of the early events of hydrogen peroxide production by
      mitochondria.
AB  - Mitochondria consume oxygen in the respiratory chain and convert redox energy
      into ATP. As a side process, they produce reactive oxygen species (ROS), whose
      physiological activities are still not understood. However, current analytical
      methods cannot be used to monitor mitochondrial ROS quantitatively and
      unambiguously. We have developed electrochemical biosensors based on peroxidase
      redox polymer-modified electrodes, providing selective detection of H2O2 with
      nanomolar sensitivity, linear response over five concentration decades, and fast
      response time. The release of H2O2 by mitochondria was then monitored under
      phosphorylating or inhibited respiration conditions. We report the detection of
      two concomitant regimes of H2O2 release: large fluxes (hundreds of nM) under
      complex III inhibition, and bursts of a few nM immediately following mitochondria
      activation. These unprecedented bursts of H2O2 are assigned to the role of
      mitochondria as the hub of redox signaling in cells.

PMID- 24854603
TI  - Adjuvant radiotherapy for lymph-node positive prostate cancer.

PMID- 24854605
TI  - Radiation dose and image quality with abdominal computed tomography with
      automated dose-optimized tube voltage selection.
AB  - OBJECTIVES: This study assessed image quality and radiation dose of multidetector
      computed tomography (CT) examination using a standard protocol and a low-voltage
      protocol. METHODS: Patients requiring contrast-enhanced abdominal CT examination
      were randomly assigned to two groups with different voltage protocols: (i) 120
      kV; (ii) an automated attenuation-based tube potential optimization mode (CARE
      kV). The volume CT dose index (CTDIvol) and dose length product (DLP) were
      recorded. Image quality was semiquantitatively assessed by two blinded
      radiologists using a five-point scale. RESULTS: There were 39 patients in the 120
      kV group and 50 patients in the CARE kV group. There was no obvious difference in
      image quality score between the groups. CARE kV resulted in a voltage reduction
      to 100 kV in 45 patients and to 80 kV in five patients. CTDIvol and DLP were
      significantly lower with CARE kV than with the 120 kV protocol. CONCLUSIONS: The
      use of CARE kV reduces radiation dose with no loss of image quality compared with
      a standard 120 kV protocol.

PMID- 24854606
TI  - Efficient access to 2,3-diarylimidazo[1,2-a]pyridines via a one-pot, ligand-free,
      palladium-catalyzed three-component reaction under microwave irradiation.
AB  - An expeditious one-pot, ligand-free, Pd(OAc)2-catalyzed, three-component reaction
      for the synthesis of 2,3-diarylimidazo[1,2-a]pyridines was developed under
      microwave irradiation. With the high availability of commercial reagents and
      great efficiency in expanding molecule diversity, this methodology is superior to
      the existing procedures for the synthesis of 2,3-diarylimidazo[1,2-a]pyridines
      analogues. 

PMID- 24854607
TI  - Snapshots.

PMID- 24854608
TI  - Alcoholic severe acute pancreatitis with positive culture of pancreatic juice
      treated by nasopancreatic drainage.
AB  - BACKGROUND: Severe acute pancreatitis (SAP) is a serious disease associated with
      alcoholism and has a high mortality rate. Effective treatments have not been
      established. METHODS: A 58-year-old man was admitted due to alcoholic SAP.
      Endoscopic retrograde cholangiopancreatography revealed pancreatic calculi at the
      pancreas head and a stricture in the pancreatic duct from the pancreas head to
      the body. Endoscopically, nasopancreatic drainage (NPD) was placed through the
      minor papilla to the pancreas tail beyond the stricture. RESULTS: Pancreatic
      juice culture was positive for Streptococcus and Enterobacter. The day after NPD,
      upper abdominal pain was relieved. After changing NPD to a pancreatic stent, the
      patient was discharged on day 21 post-NPD. CONCLUSION: Alcoholic SAP may reflect
      aggravation of chronic pancreatitis. The possibility of acute bacterial
      inflammation should be considered in all cases of chronic alcoholic pancreatitis
      who present with severe features of inflammation, even in the early stages of an
      attack. Treatment of this subset of cases by drainage could be of great
      importance and NPD may be the preferred method.

PMID- 24854609
TI  - Role of N-13 ammonia PET/CT in diagnosing pancreatic necrosis in patients with
      acute pancreatitis as compared to contrast enhanced CT--results of a pilot study.
AB  - BACKGROUND: Contrast enhanced computerized tomography (CECT) is used to determine
      severity of acute pancreatitis based upon the presence and extent of necrosis.
      However limitations do exist precluding its applicability in renal failure.
      Positron emission tomography (PET) imaging for cardiac perfusion shows good
      uptake of N-13 ammonia ((13)NH3) metabolites in pancreas owing to high perfusion.
      AIM: To evaluate the role of (13)NH3 PET/CT in acute pancreatitis and compare it
      with CECT in diagnosing and quantifying pancreatic necrosis. MATERIAL AND
      METHODS: Patients presenting within 1 week of acute pancreatitis were studied.
      Static PET images were acquired after intravenous injection of 370-740 MBq of
      (13)NH3. (13)NH3 PET/CT was followed by CECT in the absence of renal impairment.
      Maximum standard-uptake-value (SUVmax) of pancreas (P) and liver (L) were taken
      and their ratio (P/L) was estimated to determine perfusion. Areas within pancreas
      with no tracer uptake were considered necrotic. These patients were managed as
      per institutional protocol. Patients undergoing (13)NH3 PET/CT for coronary
      artery disease were used as controls. RESULTS: 29 patients (72% males) were
      studied of whom 6 had elevated serum creatinine. (13)NH3 PET/CT was done in all
      patients along with 9 controls while CECT was carried out after PET/CT in 23
      patients. Median levels of SUVmax (P/L) in the controls, uninvolved pancreas and
      necrotic areas were 1.0 (0.86-1.03), 0.66 (0.50-0.92) and 0.12 (0.07-0.21)
      respectively (p < 0.001). Necrosis estimation was similar in 22/23 patients
      without renal failure while in one patient only (13)NH3 PET/CT picked up necrosis
      (<30%). 5/6 patients with renal failure had necrosis on (13)NH(3) PET/CT which
      was confirmed on surgery or subsequent CECT after improvement of renal failure.
      CONCLUSION: This pilot study is the first in literature to diagnose necrosis in
      patients with acute pancreatitis using (13)NH3 PET/CT. With minimal additional
      radiation burden, it is possible to estimate the absolute tissue perfusion as
      well. With no adverse renal side effects, this can be an alternative to CECT in
      patients with renal failure giving similar information. It has good agreement
      with CECT with a good interobserver acceptability.

PMID- 24854610
TI  - Identification of serum microRNAs as diagnostic and prognostic biomarkers for
      acute pancreatitis.
AB  - BACKGROUND/OBJECTIVES: To identify serum microRNA (miRNA) as diagnostic and
      prognostic biomarkers for acute pancreatitis (AP). MATERIALS AND METHODS: Sera
      microRNA expression was profiled from 12 AP patients with varying disease
      severity and three healthy controls. Differentially expressed miRNAs were
      validated in a larger cohort of patients and controls. The diagnostic and
      prognostic potentials of differentially expressed miRNAs were evaluated using
      receiver operating characteristic (ROC) curve analysis and compared to that of
      classic prognostic markers for AP. RESULTS: miRNA microarray analyses identified
      205 differentially expressed miRNAs between sera from AP patients and that from
      controls. Nine miRNAs were differentially expressed between severe and mild AP
      patients. Further validation confirmed the down-regulation of miR-92b, miR-10a,
      and miR-7 in AP patients, and ROC analysis revealed that these miRNAs can
      differentiate AP from health cases. Furthermore, the serum miR-551b-5p level was
      significantly higher in patients with disease complications or a low plasma
      calcium level. ROC analysis showed that the serum miR-551b-5p level can
      distinguish between severe and mild AP. CONCLUSION: The expressions of miR-92b,
      miR-10a, and miR-7 in AP might be used for the early diagnosis of AP and miR-551b
      5p may be used for predicting AP severity.

PMID- 24854611
TI  - Early and/or immediately full caloric diet versus standard refeeding in mild
      acute pancreatitis: a randomized open-label trial.
AB  - Refeeding after acute pancreatitis (AP) is traditionally started in a
      successively increasing manner when abdominal pain is absent and pancreatic
      enzymes are decreasing. We aimed to evaluate length of hospital stay (LOHS) and
      refeeding tolerance for early refeeding and/or immediately full caloric intake in
      patients recovering from AP. METHODS: In this randomized, open-label trial,
      patients with AP were randomized into four different refeeding protocols. Group 1
      and 2 received a stepwise increasing diet during three days while 3 and 4
      received an immediately full caloric, low fat diet. Group 2 and 4 started
      refeeding early (once bowel sounds returned) and 1 and 3 started at standard time
      (bowel sounds present, no abdominal pain, no fever, leucocytes and pancreatic
      enzymes decreasing). Main outcomes measurements were LOHS and tolerance (ability
      to ingest >50% of meals without severe pain, nausea or AP relapse). RESULTS:
      Eighty patients were evaluated and 72 randomized (median age 60 years, range 24
      85, 33 male). LOHS was significantly reduced after early refeeding (median 5
      versus 7 days (p = 0.001)) but not in patients receiving immediately full caloric
      diet, compared to standard management (6 versus 6 days (p = 0.12)). There was no
      difference in refeeding tolerance comparing immediately full caloric diet versus
      stepwise increasing diet (31/35 (89%) versus 33/37 (89%) patients tolerating the
      treatment, p = 1.00) or early versus standard time for refeeding (33/37 (89%)
      versus 31/35 (89%), (p = 1.00)). CONCLUSIONS: Refeeding after AP when bowel
      sounds are present with immediately full caloric diet is safe and well tolerated.
      Early refeeding shortens LOHS.

PMID- 24854612
TI  - A randomized controlled trial of home monitoring versus hospitalization for mild
      non-alcoholic acute interstitial pancreatitis: a pilot study.
AB  - BACKGROUND/OBJECTIVES: Acute pancreatitis (AP) is a disease typically requiring
      in-hospital treatment. We conducted a trial to assess the feasibility of early
      discharge from the hospital for patients with mild non-alcoholic acute
      pancreatitis (NAAP). METHODS: Eighty-four patients with mild NAAP were randomized
      to home or hospital groups after a short hospital stay (<=24 h). AP was defined
      by the revised Atlanta criteria. Mild AP was defined as an Imrie score<=5 and a
      harmless acute pancreatitis score (HAPS)<=2 in the first 24-h of presentation. A
      nurse visited all patients in the home group on the 2nd, 3rd and 5th days. All
      patients presented for follow-up in clinic on the 7th, 14th, and 30th days. The
      primary outcome was the time to resolution of pain. Secondary outcomes evaluated
      included time to resumption of an oral diet, 30 day hospital readmission rate as
      well as the total costs associated with either approach to care. RESULTS: There
      was no difference between the groups with regards to demographics, prognostic
      severity scores, symptoms, and biliary findings. No patients developed organ
      failure, pancreatic necrosis, or died in either group. Time to the resolution of
      pain and resumption of solid food intake were similar. Three (3.6%) patients
      required readmission within 30 days, 1 from home and 2 from the hospital groups.
      The total cost was significantly less in home group ($139 +/- 73 vs. $951 +/-
      715,p < 0.001). CONCLUSIONS: Mild NAAP can be safely treated at home with regular
      visits by a nurse under the supervision of a physician. Widespread adoption of
      this practice may result in large cost savings.

PMID- 24854613
TI  - Dissecting the effect of moxifloxacin in mice with infected necrosis in
      taurocholate induced necrotizing pancreatitis.
AB  - OBJECTIVES: To investigate the limited benefit of antibiotics in ameliorating the
      outcome of acute necrotizing pancreatitis, we analyzed antibiotic therapy in
      primarily infected necrotizing pancreatitis in mice with respect to the local
      pancreatic pathology as well as systemic, pancreatitis induced adverse events.
      METHODS: Sterile pancreatic necrosis (SN) was induced by retrograde injection of
      4% taurocholate in the common bile duct of Balb/c mice. Primarily infected
      pancreatic necrosis (IN) was induced by co-injecting 10(8) CFU/ml Escherichia
      coli. 10 mg/kg of moxifloxacin was administered prior to pancreatitis induction
      (AN). After 24 h, animals were sacrificed to examine serum as well as organs for
      signs of SIRS. RESULTS: Moxifloxacin significantly reduced bacterial count in
      pancreatic lysates of animals with infected pancreatic necrosis (IN 4.1.10(7) +/-
      2.4.10(7) vs. AN 4.9.10(4) +/- 2.6.10(4) CFU/g; p < 0.001). However, it did not
      alter pancreatic histology or pulmonary damage (Histology score: IN 23.8 +/- 2.7
      vs. AN 22.6 +/- 1.7). Moxifloxacin reduced systemic immunoactivation (Serum IL-6:
      IN 330.5 +/- 336.6 vs. 38.7 +/- 25.5 pg/ml; p < 0.001), hypoglycemia (serum
      glucose: IN 105.8 +/- 12.7 vs. AN 155.7 +/- 39.5 mg/dl; p < 0.001), and serum
      aspartate aminotransferase (IN 606 +/- 89.7 vs. AN 255 +/- 52.1; p < 0.05). These
      parameters were significantly increased in animals with necrotizing pancreatitis.
      CONCLUSION: In the experimental setting, initial antibiotic therapy with
      moxifloxacin in acute infected necrotizing pancreatitis in mice does not have a
      beneficial impact on pancreatic pathology or pulmonary damage. However, other
      systemic complications induced by infected necrosis in acute pancreatitis are
      reduced by the administration of moxifloxacin.

PMID- 24854614
TI  - A comparison of the diagnostic efficacy in type 1 autoimmune pancreatitis based
      on biopsy specimens from various organs.
AB  - BACKGROUND: Comprehensive immunostaining evaluation of the biopsy specimens from
      various organs with type 1 autoimmune pancreatitis (AIP) has not been elucidated.
      Our aim was to clarify which of these biopsy specimens and counting method could
      be a useful tool for supporting the diagnosis of AIP. METHODS: We retrospectively
      evaluated biopsy specimens from pancreas (n = 19), stomach (n = 28), duodenum (n
      = 27), duodenal papilla (n = 25), colon (n = 19), liver (n = 11), bile duct (n =
      24), and minor salivary gland (n = 13) in 36 patients with AIP. Positive IgG4
      immunostaining (>10 plasma cells/high-power field [HPF]) and positive IgG4/IgG
      ratio (>40%) of biopsy specimens from 8 sites of 6 organs in one HPF and an
      average from 3 HPFs were compared between AIP and controls. RESULTS: The
      sensitivity of IgG4 immunostaining for AIP in one HPF were 16% in pancreas, 14%
      in stomach, 15% in duodenum, 52% in duodenal papilla, 11% in colon, 27% in liver,
      21% in bile duct and 8% in minor salivary gland, respectively. The positive IgG4
      immunostaining of the duodenal papilla in one HPF showed the highest sensitivity
      (52%) and accuracy (73%) among the 8 sites. It also showed the highest
      sensitivity among 4 different counting methods (IgG4 immunostaining in one HPF
      and 3 HPFs, both IgG4 immunostaining and IgG/IgG4 ratio in one HPF and 3 HPFs),
      but there were no significant differences with respect to specificity and
      accuracy. CONCLUSIONS: IgG4 immunostaining of swollen duodenal papilla with more
      than 10 IgG4-positive plasma cells in at least one HPF is useful for supporting
      the diagnosis of AIP.

PMID- 24854615
TI  - The role of CD19+ CD24high CD38high and CD19+ CD24high CD27+ regulatory B cells
      in patients with type 1 autoimmune pancreatitis.
AB  - BACKGROUND: Patients with type 1 autoimmune pancreatitis (AIP) have several
      immunologic and histologic abnormalities. It is known that depletion of B cells
      by rituximab is effective for treatment of IgG4-related disease (IgG4-RD) such as
      type 1 AIP, suggesting that B cells may be a key player in IgG4-RD. However, the
      role of regulatory B cells (Bregs) in type 1 AIP is unclear, and the objective of
      this paper is to clarify the role of Bregs in the pathophysiology of type 1 AIP
      by analyzing circulating Bregs. METHOD: We recruited 21 patients with type 1 AIP
      as determined by the International Consensus Diagnostic Criteria for AIP (ICDC).
      No patients received corticosteroid treatments. For comparison, we recruited 14
      patients with chronic pancreatitis (CP), 20 patients with pancreatic cancer, and
      25 healthy subjects as controls. We analyzed Bregs as CD19+ CD24high CD38high and
      CD19+ CD24high CD27+ from peripheral blood by flow cytometry. RESULTS: In
      peripheral blood, CD19+ CD24high CD38high Bregs were significantly increased in
      type 1 AIP patients compared with CP, pancreatic cancer, and healthy controls.
      Although not significant different, CD19+ CD24high CD27+ Bregs of type 1 AIP were
      decreased compared to those of other groups. IL-10(+) B cells were not
      significantly different from type 1 AIP patients and healthy controls. In
      untreated type 1 AIP patients, the number of CD19+ CD24high CD38high Bregs and
      IgG4 were not correlated. CONCLUSIONS: Our data suggested that CD19+ CD24high
      CD38high Bregs seemed to increase reactively to suppress the disease activity,
      and are consistent with the hypothesis that CD19+ CD24high CD27+ Bregs might be
      involved in the development of type 1 AIP, although it still remains unclear
      whether the decrease of CD19+ CD24high CD27+ cells is cause or effect of AIP.

PMID- 24854616
TI  - A sustained prostacyclin analog, ONO-1301, attenuates pancreatic fibrosis in
      experimental chronic pancreatitis induced by dibutyltin dichloride in rats.
AB  - BACKGROUND: ONO-1301, a novel sustained-release prostacyclin agonist, has an anti
      fibrotic effect on the lungs, heart, and kidneys that is partly associated with
      the induction of hepatocyte growth factor (HGF). This study examined the anti
      fibrotic effect of ONO-1301 on chronic pancreatitis (CP) progression. METHODS: CP
      was induced in rats in vivo by dibutyltin dichloride (DBTC). Seven days after
      DBTC injection (day 7), a slow-release form of ONO-1301 (10 mg/kg; ONO-1301
      treated group) or vehicle (DBTC-treated group) was injected. On days 14 and 28,
      we evaluated the histopathological CP score and mRNA expressions of HGF,
      cytokines, and collagen in the pancreas by real-time RT-PCR. In vitro, monocytes
      and pancreatic stellate cells (PSCs) were isolated from normal rat spleen and
      pancreas, respectively. The cytokine and collagen expressions of monocytes and
      PSCs were detected by real-time RT-PCR, and PSCs proliferation was examined by
      BrdU assay. RESULTS: Histopathological CP scores in vivo improved in the ONO-1301
      treated group compared to the DBTC-treated group, particularly inflammatory cell
      infiltration on day 14 and interstitial fibrosis on day 28. HGF mRNA increased
      significantly after ONO-1301 administration, whereas IL-1beta, TNF-alpha, TGF
      beta, MCP-1, and collagen mRNA decreased significantly. Cytokine expression in
      monocytes was suppressed in vitro not only by HGF, but also ONO-1301 alone.
      However, neither ONO-1301 nor HGF affected the proliferation, or cytokine or
      collagen expression of PSCs. CONCLUSIONS: ONO-1301 suppresses pancreatic fibrosis
      in the DBTC-induced CP model by inhibiting monocyte activity not only with
      induction of HGF but also by ONO-1301 itself.

PMID- 24854617
TI  - Chemotherapy for advanced pancreatic adenocarcinoma in elderly patients (>=70
      years of age): a retrospective cohort study at the National Center for Tumor
      Diseases Heidelberg.
AB  - BACKGROUND: Pancreatic cancer is mainly a disease of the elderly population, but
      clinical trials do not reflect this age distribution. Data on treatment
      strategies and outcome of older patients are limited. The aim of our study was to
      analyze safety and outcome in elderly patients with advanced pancreatic cancer
      treated with palliative chemotherapy at the outpatient clinic of the National
      Center for Tumor Diseases (NCT) at Heidelberg University Hospital. MATERIALS AND
      METHODS: We retrospectively analyzed 53 patients >=70 years using a prospectively
      maintained database. Requirements were (1) histologically proven diagnosis of
      ductal pancreatic adenocarcinoma, (2) age >=70 at time of diagnosis of advanced
      disease, and (3) measurable advanced disease. RESULTS: The median age was 73
      years. 81% of the patients received a gemcitabine-based first-line therapy.
      Median overall survival was 6.7 months. Survival differed significantly between
      patient groups with low (<=1) and high (>=2) Eastern Cooperative Oncology Group
      performance status (7.8 vs. 3.9 months, p = 0.002). 30.2% of the patients
      developed side effects resulting in dosage reductions. 39.6% of the patients
      received second-line treatment. Residual survival after disease progression was
      significantly longer for second-line treatment compared to best supportive care
      (151 vs. 39 days, p = 0.019). CONCLUSIONS: Overall, our older patients did not
      have an inferior outcome compared to the reported trial populations that included
      younger patients. Thus, palliative chemotherapy should be considered
      independently from chronological age, but the performance status should be
      carefully noticed. Second-line therapy should be considered for patients in good
      performance status after first progression.

PMID- 24854618
TI  - Rapid postoperative reduction in prognostic nutrition index is associated with
      the development of pancreatic fistula following distal pancreatectomy.
AB  - BACKGROUNDS: Despite recent advances in surgical techniques and devices for
      pancreatic remnant closure, postoperative pancreatic fistula (POPF) still remains
      one of the common complications after distal pancreatectomy (DP). Identification
      of risk factors for POPF may lead to the development of new strategies to prevent
      this ominous complication. METHODS: We retrospectively reviewed data on 44
      patients undergoing DP with the use of a stapler to identify risk factors for
      POPF. Study variables included preoperative prognostic nutritional index (PNI)
      and reduction rate of PNI on postoperative day (POD) 7. RESULTS: POPF occurred in
      23 patients (52%), of which 13 (56%) were grade B or C. Univariate analyses
      comparing patients with POPF and those without POPF showed significant
      differences in body mass index (P = 0.0102), pancreatic thickness (P = 0.0134),
      white blood cell count on POD7 (P = 0.0432), C-reactive protein level on POD7 (P
      = 0.0123), and PNI reduction rate (P = 0.0471). A multivariate analysis revealed
      pancreatic thickness (P = 0.0121) and PNI reduction rate (P = 0.0165) to be
      significant factors for POPF. Furthermore, the PNI reduction rate was
      significantly higher in patients with clinically relevant (grade B/C) POPF than
      in those with no or grade A POPF (P = 0.0257). In most patients, the massive
      postoperative PNI reduction preceded the diagnosis of clinically relevant POPF.
      CONCLUSIONS: These findings suggest that rapid postoperative reduction in PNI is
      associated with the development of POPF.

PMID- 24854619
TI  - Ring-enhancement pattern on contrast-enhanced CT predicts adenosquamous carcinoma
      of the pancreas: a matched case-control study.
AB  - OBJECTIVES: Adenosquamous carcinoma of the pancreas (ASC) is a rare malignant
      neoplasm of the pancreas, exhibiting both glandular and squamous differentiation.
      However, little is known about its imaging features. This study examined the
      imaging features of pancreatic ASC. METHODS: We evaluated images of contrast
      enhanced computed tomography (CT) and endoscopic ultrasonography (EUS). As
      controls, solid pancreatic neoplasms matched in a 2:1 ratio to ASC cases for age,
      sex and tumor location were also evaluated. RESULTS: Twenty-three ASC cases were
      examined, and 46 solid pancreatic neoplasms (43 pancreatic ductal
      adenocarcinomas, two pancreatic neuroendocrine tumors and one acinar cell
      carcinoma) were matched as controls. Univariate analysis demonstrated significant
      differences in the outline and vascularity of tumors on contrast-enhanced CT in
      the ASC and control groups (P < 0.001 and P < 0.001, respectively). A smooth
      outline, cystic changes, and the ring-enhancement pattern on contrast-enhanced CT
      were seen to have significant predictive powers by stepwise forward logistic
      regression analysis (P = 0.044, P = 0.010, and P = 0.001, respectively). Of the
      three, the ring-enhancement pattern was the most useful, and its predictive
      diagnostic sensitivity, specificity, positive predictive value and negative
      predictive value for diagnosis of ASC were 65.2%, 89.6%, 75.0% and 84.3%,
      respectively. CONCLUSIONS: These results demonstrate that presence of the ring
      enhancement pattern on contrast-enhanced CT is the most useful predictive factor
      for ASC.

PMID- 24854620
TI  - Pancreatic abnormalities detected by endoscopic ultrasound (EUS) in patients
      without clinical signs of pancreatic disease: any difference between standard and
      Rosemont classification scoring?
AB  - BACKGROUND: The prevalence of nine EUS features of chronic pancreatitis (CP)
      according to the standard Wiersema classification has been investigated in 489
      patients undergoing EUS for an indication not related to pancreatico-biliary
      disease. We showed that 82 subjects (16.8%) had at least one ductular or
      parenchymal abnormality. Among them, 18 (3.7% of study population) had >=3
      Wiersema criteria suggestive of CP. Recently, a new classification (Rosemont) of
      EUS findings consistent, suggestive or indeterminate for CP has been proposed.
      AIM: To stratify healthy subjects into different subgroups on the basis of EUS
      features of CP according to the Wiersema and Rosemont classifications and to
      evaluate the agreement in the diagnosis of CP with the two scoring systems.
      Weighted kappa statistics was computed to evaluate the strength of agreement
      between the two scoring systems. Univariate and multivariate analysis between any
      EUS abnormality and habits were performed. RESULTS: Eighty-two EUS videos were
      reviewed. Using the Wiersema classification, 18 subjects showed >=3 EUS features
      suggestive of CP. The EUS diagnosis of CP in these 18 subjects was considered as
      consistent in only one patient, according to Rosemont classification. Weighted
      Kappa statistics was 0.34 showing that the strength of agreement was 'fair'.
      Alcohol use and smoking were identified as risk factors for having pancreatic
      abnormalities on EUS. CONCLUSIONS: The prevalence of EUS features consistent or
      suggestive of CP in healthy subjects according to the Rosemont classification is
      lower than that assessed by Wiersema criteria. In that regard the Rosemont
      classification seems to be more accurate in excluding clinically relevant CP.
      Overall agreement between the two classifications is fair.

PMID- 24854623
TI  - Solvent extraction of lanthanides and yttrium from aqueous solution with
      methylimidazole in an ionic liquid.
AB  - 1-Methylimidazole (1-MIM) and 2-methylimidazole (2-MIM) are miscible in water and
      imidazolium based ionic liquids (ILs), and can coordinate with soft metal ions.
      This paper reports a novel solvent extraction process for trivalent lanthanides
      and yttrium from aqueous solutions into ILs, which was promoted by a hydrophilic
      1-MIM or 2-MIM. Slope analysis confirmed that MIM in ILs formed a 1 : 1 complex
      with La(3+) and Y(3+) and a 1 : 4 complex with Eu(3+) and Lu(3+), depending on
      the atomic number of the metal and the metal-ligand interactions that have been
      characterized by FTIR spectroscopy and ESI-MS. The effect of nitrate
      concentration on the extraction of lanthanides with 1-MIM in ILs was analysed. It
      indicated that nitrate anions were involved in the extraction process. Under the
      same conditions, the extraction of lanthanides with MIM into n-pentanol was
      carried out. The extractability was by far lower than that obtained in ILs. Both
      cationic exchange and neutral solvation mechanisms occurred in ILs and only the
      neutral solvation mechanism occurred in n-pentanol, which were demonstrated by
      the extraction tests and the structure of extracted species determined by ESI-MS.
      The competitive extraction in ILs showed good selectivity for lanthanides
      compared to alkali metals and alkaline earth cations. After extraction,
      lanthanides could be stripped very easily from the ionic liquid phase with dilute
      nitric acid. From the temperature dependence data, the thermodynamic parameter
      values (DeltaH, DeltaS and DeltaG) were calculated. The results indicated that
      the extraction reactions were spontaneous and went through an endothermic
      process. 

PMID- 24854621
TI  - Disparate HDV ribozyme crystal structures represent intermediates on a rugged
      free-energy landscape.
AB  - The hepatitis delta virus (HDV) ribozyme is a member of the class of small, self
      cleaving catalytic RNAs found in a wide range of genomes from HDV to human. Both
      pre- and post-catalysis (precursor and product) crystal structures of the cis
      acting genomic HDV ribozyme have been determined. These structures, together with
      extensive solution probing, have suggested that a significant conformational
      change accompanies catalysis. A recent crystal structure of a trans-acting
      precursor, obtained at low pH and by molecular replacement from the previous
      product conformation, conforms to the product, raising the possibility that it
      represents an activated conformer past the conformational change. Here, using
      fluorescence resonance energy transfer (FRET), we discovered that cleavage of
      this ribozyme at physiological pH is accompanied by a structural lengthening in
      magnitude comparable to previous trans-acting HDV ribozymes. Conformational
      heterogeneity observed by FRET in solution appears to have been removed upon
      crystallization. Analysis of a total of 1.8 usec of molecular dynamics (MD)
      simulations showed that the crystallographically unresolved cleavage site
      conformation is likely correctly modeled after the hammerhead ribozyme, but that
      crystal contacts and the removal of several 2'-oxygens near the scissile
      phosphate compromise catalytic in-line fitness. A cis-acting version of the
      ribozyme exhibits a more dynamic active site, while a G-1 residue upstream of the
      scissile phosphate favors poor fitness, allowing us to rationalize corresponding
      changes in catalytic activity. Based on these data, we propose that the available
      crystal structures of the HDV ribozyme represent intermediates on an overall
      rugged RNA folding free-energy landscape. 

PMID- 24854622
TI  - A central role for the primary microRNA stem in guiding the position and
      efficiency of Drosha processing of a viral pri-miRNA.
AB  - Processing of primary microRNA (pri-miRNA) stem-loops by the Drosha-DGCR8 complex
      is the initial step in miRNA maturation and crucial for miRNA function.
      Nonetheless, the underlying mechanism that determines the Drosha cleavage site of
      pri-miRNAs has remained unclear. Two prevalent but seemingly conflicting models
      propose that Drosha-DGCR8 anchors to and directs cleavage a fixed distance from
      either the basal single-stranded (ssRNA) or the terminal loop. However, recent
      studies suggest that the basal ssRNA and/or the terminal loop may influence the
      Drosha cleavage site dependent upon the sequence/structure of individual pri
      miRNAs. Here, using a panel of closely related pri-miRNA variants, we further
      examine the role of pri-miRNA structures on Drosha cleavage site selection in
      cells. Our data reveal that both the basal ssRNA and terminal loop influence the
      Drosha cleavage site within three pri-miRNAs, the Simian Virus 40 (SV40) pri
      miRNA, pri-miR-30a, and pri-miR-16. In addition to the flanking ssRNA regions, we
      show that an internal loop within the SV40 pri-miRNA stem strongly influences
      Drosha cleavage position and efficiency. We further demonstrate that the
      positions of the internal loop, basal ssRNA, and the terminal loop of the SV40
      pri-miRNA cooperatively coordinate Drosha cleavage position and efficiency. Based
      on these observations, we propose that the pri-miRNA stem, defined by internal
      and flanking structural elements, guides the binding position of Drosha-DGCR8,
      which consequently determines the cleavage site. This study provides mechanistic
      insight into pri-miRNA processing in cells that has numerous biological
      implications and will assist in refining Drosha-dependent shRNA design. 

PMID- 24854624
TI  - 14-Thienyl methylene matrine (YYJ18), the derivative from matrine, induces
      apoptosis of human nasopharyngeal carcinoma cells by targeting MAPK and PI3K/Akt
      pathways in vitro.
AB  - BACKGROUND/AIMS: Nasopharyngeal carcinoma (NPC) is a distinctive type of head and
      neck cancer with the highest incidence in South China. Previous studies have
      proved that matrine, a main alkaloid isolated from Sophora flavescens Ait, has
      antitumor activity against NPC. However, the effect is not so pronounced and the
      underlying mechanism remains largely unclear. Here we investigated whether 14
      thienyl methylene matrine (YYJ18) that was derived from matrine could exert more
      effective suppression activity on NPC, along with the underlying mechanism.
      METHODS: NPC cell lines CNE1, CNE2 and HONE1 were treated with YYJ18. Cell
      proliferation and apoptosis were determined by MTT assay and flow cytometry.
      Activation of mitogen-activated protein kinases (MAPK) and phosphatidylinositol 3
      kinase/protein kinase B (PI3K/Akt) pathways were determined by Western blotting
      and quantitative RT-PCR. RESULTS: YYJ18 remarkably inhibited proliferation and
      induced apoptosis of all three NPC cell lines in a dose-dependent manner,
      especially in CNE2 cells. Furthermore, YYJ18 treatment significantly suppressed
      phosphorylation of p38 in CNE2 cells, but upregulated phosphorylation of
      extracellular signal-regulated kinase1/2 (ERK1/2) and Akt. Next, alterations in
      downstream signaling were found, including activation of BCL2-associated X
      protein (Bax), caspase-3 and inactivation of B-cell CLL/lymphoma 2 (Bcl-2).
      CONCLUSION: We demonstrate the potent inhibitory effects of 14-thienyl methylene
      matrine on NPC cells for the first time, which could be mediated by modulation of
      MAPK and PI3K/Akt pathways.

PMID- 24854625
TI  - Vitamin D deficiency in pregnant women of ethnic minority: a potential
      contributor to preeclampsia.
AB  - OBJECTIVE: We investigated risk for comorbidities and preeclampsia at low vitamin
      D levels in ethnic minorities. STUDY DESIGN: Umbilical cord vitamin D (25(OH)D)
      concentration was determined in urban minorities: 80.9% African American and 17%
      Hispanic mothers-baby pairs. To identify the correlation between vitamin D levels
      and high-risk comorbidities which result in preeclampsia, multivariate logistic
      regression analyses were performed. RESULT: Below the Institute of Medicine
      threshold of 25(OH)D for pregnant women (25 ng ml-1), obesity (P=0.055) and
      pregestational diabetes (odds ratio (OR)=2.056) were observed. The study median
      was 16 ng ml-1 (<25th percentile), at which gestational hypertension (P=0.042),
      chronic hypertension (OR=4.842) and pregestational diabetes (OR=3.45) became
      relevant. The risk for preeclampsia increased 12-fold with gestational
      hypertension (P=0.003) and 14-fold with combined chronic and gestational
      hypertension (P=0.001). CONCLUSION: Pregnant women of ethnic minority had lower
      median vitamin D levels which may contribute to a potential risk for
      preeclampsia.

PMID- 24854626
TI  - Paracetamol treatment of patent ductus arteriosus in preterm infants.
AB  - OBJECTIVE: To determine the effectiveness of paracetamol in closing patent ductus
      arteriosus (PDA) in preterm infants of our population. STUDY DESIGN: Infants with
      symptomatic PDA who failed or could not get ibuprofen treatment, and who were
      candidates for surgical ligation, were administered oral paracetamol 15 mg kg-1
      every 6h, for up to 7 days and were monitored for clinical, echocardiographic and
      laboratorial courses. RESULT: Seven infants, between 24-27 weeks' gestation, were
      included. In four the DA was closed while treated by paracetamol-in one of them
      the DA reopened, treated with paracetamol again, and closed. In one infant, the
      DA almost closed, symptoms disappeared, and the DA subsequently closed
      spontaneously later. Two needed surgical ligation. There were no hematologic or
      biochemical abnormalities. CONCLUSION: Although there is the possibility that PDA
      may have closed spontaneously, it is proposed that paracetamol could contribute
      to the closure of PDA in preterm infants.

PMID- 24854627
TI  - Effect of hydration on plasmonic coupling of bioconjugated gold nanoparticles
      immobilized on a gold film probed by surface-enhanced Raman spectroscopy.
AB  - Gold nanoparticle (AuNP)-Au film constructs were prepared using antibody-antigen
      interactions or a small organic cross-linker to systematically control the gap
      between the AuNP and Au film. Surface-enhanced Raman spectroscopy (SERS),
      scanning electron micrsocopy (SEM), and atomic force microscopy (AFM) were used
      to characterize each construct and elucidate structure-activity relationships.
      Interestingly, plasmonic coupling and SERS intensity were reversibly modulated
      with wetting/drying cycles for the protein immobilized AuNP, and this effect was
      attributed to changes in protein size with hydration state. This work provides
      insight into fundamental limitations of AuNP-enabled SERS bioassays and will
      facilitate rational design of novel biospecific ligands that maximize SERS
      sensitivity. 

PMID- 24854629
TI  - Self-reported habitual snoring and risk of cardiovascular disease and all-cause
      mortality.
AB  - OBJECTIVE: Inconsistent findings have reported the association between self
      reported habitual snoring and risk of cardiovascular disease (CVD) and all-cause
      mortality. We conducted a meta-analysis to investigate whether self-reported
      habitual snoring was an independent predictor for CVD and all-cause mortality
      using prospective observational studies. METHODS: Electronic literature databases
      (PubMed, Medline, Embase, Cochrane Library, Wanfang database, and China National
      Knowledge Infrastructure) were searched for publications prior to September 2013.
      Only prospective studies evaluating baseline habitual snoring and subsequent risk
      of CVD and all-cause mortality were selected. Pooled adjust hazard risk (HR) and
      corresponding 95% confidence intervals (CI) were calculated for categorical risk
      estimates. RESULTS: Eight studies with 65,037 subjects were analyzed. Pooled
      adjust HR was 1.26 (95% CI 0.98-1.62) for CVD, 1.15 (95% CI 1.05-1.27) for
      coronary heart disease (CHD), and 1.26 (95% CI 1.11-1.43) for stroke comparing
      habitual snoring to non-snorers. Pooled adjust HR was 0.98 (95% CI 0.78-1.23) for
      all-cause mortality in a random effect model comparing habitual snoring to non
      snorers. Habitual snoring appeared to increase greater stroke risk among men (HR
      1.54; 95% CI: 1.09-2.17) than those in women (HR 1.22; 95% CI: 1.05-1.41).
      CONCLUSIONS: Self-reported habitual snoring is a mild but statistically
      significant risk factor for stroke and CHD, but not for CVD and all-cause
      mortality. However, whether the risk is attributable to obstructive sleep apnea
      syndrome or snoring alone remains controversial.

PMID- 24854631
TI  - Cannabidiol and medical marijuana for the treatment of epilepsy.

PMID- 24854630
TI  - Increased expression of GCNT1 is associated with altered O-glycosylation of PSA,
      PAP, and MUC1 in human prostate cancers.
AB  - BACKGROUND: Protein glycosylation is a common posttranslational modification and
      glycan structural changes have been observed in several malignancies including
      prostate cancer. We hypothesized that altered glycosylation could be related to
      differences in gene expression levels of glycoprotein synthetic enzymes between
      normal and malignant prostate tissues. METHODS: We interrogated prostate cancer
      gene expression data for reproducible changes in expression of glycoprotein
      synthetic enzymes. Over-expression of GCNT1 was validated in prostate samples
      using RT-PCR. ELISA was used to measure core 2 O-linked glycan sialyl Lewis X
      (sLe(x) ) of prostate specific antigen (PSA), Mucin1 (MUC1), and prostatic acidic
      phosphatase (PAP) proteins. RESULTS: A key glycosyltransferase, GCNT1, was
      consistently over-expressed in several prostate cancer gene expression datasets.
      RT-PCR confirmed increased transcript levels in cancer samples compared to normal
      prostate tissue in fresh-frozen prostate tissue samples. ELISA using PSA, PAP,
      and MUC1 capture antibodies and a specific core 2 O-linked sLe(x) detection
      antibody demonstrated elevation of this glycan structure in cancer compared to
      normal tissues for MUC1 (P = 0.01), PSA (P = 0.03) and near significant
      differences in PAP sLe(x) levels (P = 0.06). MUC1, PSA and PAP protein levels
      alone were not significantly different between paired normal and malignant
      prostate samples. CONCLUSIONS: GCNT1 is over-expressed in prostate cancer and is
      associated with higher levels of core 2 O-sLe(x) in PSA, PAP and MUC1 proteins.
      Alterations of O-linked glycosylation could be important in prostate cancer
      biology and could provide a new avenue for development of prostate cancer
      specific glycoprotein biomarkers.

PMID- 24854628
TI  - ABCA1 gene variation and heart disease risk reduction in the elderly during
      pravastatin treatment.
AB  - AIMS: Our goals were to examine the relationships of a specific ATP-binding
      cassette transporter A1 (ABCA1) variant, rs2230806 (R219K), on baseline lipids,
      low-density lipoprotein cholesterol (LDL-C) lowering due to pravastatin, baseline
      heart disease, and cardiac endpoints on trial. METHODS AND RESULTS: The ABCA1
      R219K variant was assessed in 5414 participants in PROSPER (PROspective Study of
      Pravastatin in the Elderly at Risk) (mean age 75.3 years), who had been
      randomized to pravastatin 40 mg/day or placebo and followed for a mean of 3.2
      years. Of these subjects 47.6% carried the variant, with 40.0% carrying one
      allele, and 7.6% carrying both alleles. No effects on baseline LDL-C levels were
      noted, but mean HDL-C increased modestly according to the number of variant
      alleles being present (1.27 vs 1.28 vs 1.30 mmol/L, p = 0.024). No relationships
      between the presence or absence of this variant and statin induced LDL-C lowering
      response or CHD at baseline were noted. However within trial those with the
      variant as compared to those without the variant, the overall adjusted hazard
      ratio for new cardiovascular disease (fatal CHD, non-fatal myocardial infarction,
      or fatal or non-fatal stroke) was 1.22 (95% CI 1.06-1.40, p = 0.006), while for
      those in the pravastatin group it was 1.41 (1.15-1.73, p = 0.001), and for those
      in the placebo group it was 1.08 (0.89-1.30, p = 0.447) (p for interaction
      0.058). CONCLUSION: Our data indicate that subjects with the ABCA1 R219K variant
      may get significantly less heart disease risk reduction from pravastatin
      treatment than those without the variant.

PMID- 24854632
TI  - Direct fabrication of graphene on SiO2 enabled by thin film stress engineering.
AB  - We demonstrate direct production of graphene on SiO2 by CVD growth of graphene at
      the interface between a Ni film and the SiO2 substrate, followed by dry
      mechanical delamination of the Ni using adhesive tape. This result is enabled by
      understanding of the competition between stress evolution and microstructure
      development upon annealing of the Ni prior to the graphene growth step. When the
      Ni film remains adherent after graphene growth, the balance between residual
      stress and adhesion governs the ability to mechanically remove the Ni after the
      CVD process. In this study the graphene on SiO2 comprises micron-scale domains,
      ranging from monolayer to multilayer. The graphene has >90% coverage across
      centimeter-scale dimensions, limited by the size of our CVD chamber. Further
      engineering of the Ni film microstructure and stress state could enable
      manufacturing of highly uniform interfacial graphene followed by clean mechanical
      delamination over practically indefinite dimensions. Moreover, our findings
      suggest that preferential adhesion can enable production of 2-D materials
      directly on application-relevant substrates. This is attractive compared to
      transfer methods, which can cause mechanical damage and leave residues behind. 

PMID- 24854634
TI  - Multiple sclerosis fatigue relief by bilateral somatosensory cortex
      neuromodulation.
AB  - Multiple sclerosis-related fatigue is highly common and often refractory to
      medical therapy. Ten fatigued multiple sclerosis patients received two blocks of
      5-day anodal bilateral primary somatosensory areas transcranial direct current
      stimulation in a randomized, double-blind sham-controlled, cross-over study. The
      real neuromodulation by a personalized electrode, shaped on the MR-derived
      primary somatosensory cortical strip, reduced fatigue in all patients, by 26 % in
      average (p = 0.002), which did not change after sham (p = 0.901). Anodal tDCS
      over bilateral somatosensory areas was able to relief fatigue in mildly disabled
      MS patients, when the fatigue-related symptoms severely hamper their quality of
      life. These small-scale study results support the concept that interventions
      modifying the sensorimotor network activity balances could be a suitable non
      pharmacological treatment for multiple sclerosis fatigue.

PMID- 24854636
TI  - Introduction.

PMID- 24854633
TI  - Identification and characterization of small molecule human papillomavirus E6
      inhibitors.
AB  - Cervical cancer is the sixth most common cancer in women worldwide and the
      leading cause of women's death in developing countries. Nearly all cervical
      cancers are associated with infection of the human papillomavirus (HPV). This
      sexually transmitted pathogen disrupts the cell cycle via two oncoproteins: E6
      and E7. Cells respond to E7-mediated degradation of pRB by upregulating the p53
      tumor suppressor pathway. However, E6 thwarts this response by binding to the
      cellular E6-Associating Protein (E6AP) and targeting p53 for degradation. These
      two virus-facilitated processes pave the way for cellular transformation.
      Prophylactic HPV vaccines are available, but individuals already infected with
      HPV lack drug-based therapeutic options. To fill this void, we sought to identify
      small molecule inhibitors of the E6-E6AP interaction. We designed an ELISA-based
      high throughput assay to rapidly screen compound libraries, and hits were
      confirmed in several orthogonal biochemical and cell-based assays. Over 88,000
      compounds were screened; 30 had in vitro potencies in the mid-nanomolar to mid
      micromolar range and were classified as validated hits. Seven of these hits
      inhibited p53 degradation in cell lines with HPV-integrated genomes. Two
      compounds of similar scaffold successfully blocked p53 degradation and inhibited
      cell proliferation in cells stably transfected with E6. Together, these studies
      suggest that small molecules can successfully block E6-dependent p53 degradation
      and restore p53 activity. The compounds identified here constitute attractive
      starting points for further medicinal chemistry efforts and development into
      beneficial therapeutics. 

PMID- 24854637
TI  - Stem cells and regeneration in plants.
AB  - BACKGROUND: Plants are characterized by indeterminate post-embryonic development
      that is evident, for example, in the continuous branching of shoots and roots.
      High competence to regenerate tissues is another consequence of such intrinsic
      developmental plasticity in plants. It has been suggested that specialized groups
      of cells within plant meristems should be compared to stem cells in animals, but
      the utility of this label in the context of post-embryonic plant development and
      regeneration is often debated. SUMMARY: This paper is organized into 3 short
      sections, where (a) key observations and experimental results on tissue
      regeneration in plants - mainly in the model system Arabidopsis thaliana, (b)
      stem cell activity and (c) their role in regeneration are described. The main
      focus is maintained on the critical aspects of defining stem cell-ness in plants,
      particularly in the context of tissue regeneration. A number of recent excellent
      reviews are cited throughout the text to give the reader the appropriate tools to
      dig deeper into the various stimulating topics introduced here. KEY MESSAGES:
      Despite the remarkable somatic developmental plasticity characterizing post
      embryonic development in plants, use of the classic concept of stem cells has
      been imported from the animal literature with the goal of facilitating our
      understanding and description of plant developmental processes. It is not clear
      if this is the case, especially in light of the recent experimental results on
      root regeneration in Arabidopsis mutants.

PMID- 24854638
TI  - Kidney development: an overview.
AB  - BACKGROUND: Kidney diseases are worldwide public health problems with a high cost
      and increasing incidence. By revealing the genetic and cellular mechanism behind
      mammalian kidney development, better diagnostic methods and novel therapies can
      be expected to be developed. The mammalian kidney is a typical organ that
      develops on the basis of sequential and reciprocal cell and tissue interactions.
      Functional genetic analysis has identified that genes from different classes are
      involved in the construction of the kidney and the same genes are also connected
      to the development of diseases. SUMMARY: This review gives an overview of the
      basics of kidney ontogeny, from identification of the primary kidney cell to
      inductive signals of ureter budding and formation of the segmented nephron. We
      also go through some of the key factors involved in the control of morphogenesis.
      KEY MESSAGE: Despite the wealth of accumulated data on nephron development,
      including progenitor cell control factors and inductive signals, many of the
      detailed mechanisms remain to be revealed.

PMID- 24854639
TI  - Kidney regeneration in fish.
AB  - BACKGROUND: Chronic and acute kidney injury damages nephrons, the blood filtering
      tubules in the kidney. Although mammalian kidneys can regenerate the tubular
      epithelium of the nephron, no new nephrons are made during adulthood. In
      contrast, fish are capable of growing nephrons de novo throughout their life. A
      better understanding of this 'neo-nephrogenic' response in fish may lead to the
      development of novel regenerative therapies to treat kidney disease in humans.
      SUMMARY: In this review, nephron formation in the fish mesonephric kidney during
      normal growth and in response to acute injury is examined at the morphological
      and molecular levels. Included is an overview of the recent discovery of
      migratory nephron progenitors that, following transplantation, can engraft host
      kidneys and give rise to functional nephrons. KEY MESSAGES: Mesonephric nephron
      progenitors appear during the larval stage, migrate together to form clusters,
      activate the expression of conserved nephrogenic genes, and epithelialize into
      nascent nephrons in a process that resembles mammalian nephron formation. Nephron
      progenitors persist in the adult fish kidney and continue to add new nephrons at
      a basal rate as the fish grows in size. Following acute kidney injury, nephron
      formation is significantly increased, allowing the fish to rapidly regenerate
      lost nephrons. Transplantation of nephron progenitors into the kidney results in
      the formation of donor-derived nephrons in the recipient fish.

PMID- 24854635
TI  - The gender-specific association of CXCL16 A181V gene polymorphism with
      susceptibility to multiple sclerosis, and its effects on PBMC mRNA and plasma
      soluble CXCL16 levels: preliminary findings.
AB  - CXC ligand 16 (CXCL16) is a multifunctional chemokine involved in cell adhesion
      and chemoattraction as well as in the scavenging of oxidized lipoproteins.
      Experimental data suggest the roles of CXCL16 in pathogenesis of multiple
      sclerosis (MS). A181V polymorphism in the human CXCL16 gene has been associated
      with the clinical course of certain chronic inflammatory diseases. The aim of
      this study was to analyze the effects of CXCL16 A181V polymorphism on: (1)
      susceptibility to MS and disease course, (2) peripheral blood mononuclear cells
      (PBMC) CXCL16 mRNA levels and plasma soluble CXCL16 levels of patients with MS
      and healthy controls. In this study, 459 MS patients and 303 controls were
      included. Real-time PCR-based methods were applied for genotyping of CXCL16 A181V
      and for CXCL16 gene expression analysis. Quantitative sandwich enzyme immunoassay
      was performed for quantification of plasma soluble CXCL16. CXCL16 AA genotype had
      a significant protective effect on MS susceptibility in women (OR = 0.53, +/-95 %
      CI = 0.35-0.82, p = 0.004). The V allele-containing genotypes were associated
      with significantly higher CXCL16 mRNA levels in PBMC of both female (mean factor
      = 1.81, S.E. = 1.14-2.77, p < 0.01) and male (mean factor = 1.58, S.E. = 1.35
      1.73, p < 0.01) controls. No significant association of the CXCL16 polymorphism
      was established either with soluble CXCL16 plasma levels or with clinical
      parameters and course of MS. The main finding of this study is gender-specific
      association of CXCL16 A181V polymorphism with susceptibility to MS in females.
      The current results should be replicated and validated in the larger sample
      group.

PMID- 24854640
TI  - Kidney regeneration in mammals.
AB  - BACKGROUND: Several organs such as the skin and liver have a great capacity for
      regeneration. However, many approaches only delay the progression of end-stage
      kidney disease and do not achieve efficient long-term stabilization, let alone
      regeneration. SUMMARY: In mammals, the kidney has an innate but limited capacity
      for regeneration which can only modify the nephron structure and function but not
      increase the nephron number. Several clinical and animal studies have indicated
      that functional improvements and/or structural regression can occur in chronic
      kidney disease. Cell reconstitution, matrix remodeling, and tissue reorganization
      are major mechanisms for kidney regeneration. Current approaches achieve only
      partial kidney regeneration, but this does not occur in all animals and is not
      sustained in the long term. Multipronged and early interventions are future
      choices for the induction of kidney regeneration. KEY MESSAGES: Kidney
      regeneration in mammals is feasible but limited and may be enhanced by
      multitargeting key mechanisms.

PMID- 24854641
TI  - Kidney regeneration with stem cells: an overview.
AB  - BACKGROUND: Kidney regeneration is currently gaining considerable attention in
      place of kidney dialysis as the ultimate therapeutic strategy for renal failure.
      However, because of anatomical complications, the kidney is believed to be the
      hardest organ to regenerate. Such a complicated organ is virtually impossible to
      imagine being completely rebuilt de novo from stem cells. Nevertheless, several
      research groups are attempting this large challenge. SUMMARY: There are 4 major
      strategies for de novo kidney regeneration from stem cells. These strategies
      include the use of: (i) a decellularized cadaveric scaffold, (ii) blastocyst
      decomplementation, (iii) a nephrogenic niche for growing a xeno-embyro, and (iv)
      self-assembly potential. All of these strategies may be applicable in the
      clinical setting, but a substantial preparation period appears to be required.
      KEY MESSAGES: Although many outstanding problems remain for kidney regeneration,
      including ethical issues and the formation of chimeric structures, trials provide
      hope for dialysis patients and kidney regeneration is expected to be a reality in
      the future.

PMID- 24854642
TI  - Cell therapy for kidney injury: different options and mechanisms--mesenchymal and
      amniotic fluid stem cells.
AB  - BACKGROUND: Acute kidney injury (AKI) is emerging as a public health problem in
      developing and developed countries. It affects up to 7% of hospitalized patients,
      with a higher prevalence in critical care units. Despite major advances in
      preventive strategies and support measures, the mortality rate among patients
      remains higher than 50%. Several pharmacological approaches to improve renal
      function and survival after an AKI episode have been largely unsuccessful in
      clinical practice. SUMMARY: Stem cell-based therapy has provided new hopes of
      innovative interventions to enhance the limited capability of kidney regeneration
      in AKI. An important target for cell therapy is represented by tubular epithelial
      cells which after acute ischemic or toxic insults undergo dysfunction and
      detachment. Among adult stem cells, mesenchymal stromal/stem cells (MSC) are an
      attractive therapeutic tool by virtue of their unique biological properties,
      tropism for damaged tissues, and proregenerative capacity. In the present review,
      we discuss the mechanisms underlying the renoprotective effects of therapies with
      stem cells of different origins in preclinical models of AKI by evaluating new
      modalities by which MSC interact with damaged cells via the release of soluble
      factors and exosomes/microvesicles. Several biological effects, including
      antiapoptotic, promitogenic, immunomodulatory, and anti-inflammatory activities,
      have been analyzed in renal tissue of AKI animals receiving stem cell treatments.
      The mechanisms of stem cell homing and engraftment to sites of tissue damage have
      also been discussed. KEY MESSAGES: The translation of preclinical data on stem
      cells into effective and safe new modalities of care is still limited, and
      further studies are needed before their application in patients with AKI.

PMID- 24854643
TI  - Cell therapy for kidney injury: different options and mechanisms--kidney
      progenitor cells.
AB  - BACKGROUND: Since no specific or radical treatments have yet been established for
      acute kidney injury (AKI), the development of cell transplantation therapy using
      renal progenitors is desirable as a new therapeutic option for AKI. The recent
      advances in developmental biology, stem cell biology, and nephrology have led to
      an increased availability of renal progenitors from multiple sources. SUMMARY:
      Four main sources of renal progenitors have been described so far: isolation from
      (1) embryonic or (2) adult kidneys, (3) directed differentiation of pluripotent
      stem cells such as embryonic stem cells (ESCs) and induced pluripotent stem cells
      (iPSCs), and (4) cellular reprogramming of fully differentiated adult renal
      cells. Renal progenitors from adult kidneys may not be equivalent to those from
      embryonic kidneys, and they contain several different cell populations identified
      by various methods. The methods used for the directed differentiation of
      ESCs/iPSCs and reprogramming of differentiated adult renal cells into renal
      progenitors have not been fully established. The therapeutic effects of
      progenitor cell transplantation in AKI animal models have been examined in a
      small number of reports using renal progenitors from adult kidneys, while no
      reports have described the therapeutic potential of renal progenitors from other
      sources. KEY MESSAGES: Renal progenitor transplantation might provide a novel
      therapeutic strategy for AKI. Further research efforts toward the clinical
      application of this strategy are needed, including a detailed characterization of
      embryonic or adult renal progenitors and the development of in vitro expansion
      methods and therapeutically effective transplantation methods for these cell
      types. More experience and knowledge should be accumulated regarding the directed
      differentiation of pluripotent stem cells and cellular reprogramming to generate
      renal progenitor cells.

PMID- 24854644
TI  - Glomerular regeneration: when can the kidney regenerate from injury and what
      turns failure into success?
AB  - BACKGROUND: For many years, the glomerulus was considered incapable of
      regeneration. However, experimental and clinical evidence challenged this concept
      and showed that glomerular injury and even glomerulosclerosis can undergo
      regression under certain circumstances. The problem with glomerular regeneration
      is centered around the podocyte, a highly specialized cell that is the critical
      constituent of the glomerular filtration barrier. SUMMARY: Podocytes are
      characterized by a complex cytoskeleton that makes them unable to proliferate.
      Thus, once their depletion reaches a specific threshold, it is considered to be
      irreversible. The discovery of cells with the aptitude to differentiate into
      podocytes in the adult kidney, i.e. renal progenitor cells (RPCs), was a critical
      step in understanding the mechanisms of glomerular repair. Accumulating evidence
      suggests that a tight regulation of many different signaling pathways, such as
      Notch, Wnt, and microRNA, is involved in a correct regenerative process and that
      an altered regulation of these same signaling pathways in RPCs triggers the
      generation of focal segmental glomerulosclerosis lesions. In particular,
      regeneration is severely impaired by proteinuria, when albumin sequesters
      retinoic acid and blocks RPC differentiation in podocytes. KEY MESSAGES: RPC
      maintenance and differentiating potential are regulated by complex mechanisms
      that can be implemented following glomerular injury and can be manipulated to
      activate regeneration for therapeutic purposes. A better understanding of the
      phenomenon of glomerular regeneration paves the way for the prevention and
      treatment of glomerular diseases.

PMID- 24854645
TI  - Tubular regeneration: when can the kidney regenerate from injury and what turns
      failure into success?
AB  - BACKGROUND: The most common intrarenal cause for acute kidney injury/renal
      failure is tubular damage. The kidney tubules are arranged as compartments of
      cellular mosaics to perform their functions, and at rest almost a fifth of the
      human ATP consumption is allotted to the reabsorption of substances from the
      filtrate, rendering especially the proximal tubules highly sensitive to oxygen
      and/or nutrient deprivation. Normally mitotically quiescent, the tubular
      epithelium shows a brisk regenerative response following injury if supportive
      care is offered, allowing functional restoration. Despite this, the cellular
      machinery behind the regenerative capacity is still not unequivocally defined.
      This is at odds with other epithelia such as those of the skin and intestine,
      where stem cells maintain a continuous flow of new cells from designated niches.
      SUMMARY: This review discusses the classical concept of renal regeneration, i.e.
      stochastically surviving cells undergoing dedifferentiation (or epithelial
      mesenchymal transition) followed by replenishment of the tubular epithelium.
      Furthermore however, this view has recently been challenged by the concept of
      organ-confined stem/progenitor cells, bone marrow-derived stem cells, or
      mesenchymal stem cells taking part in the regenerative events. Whereas results
      from animal models support the classical view, morphologically distinct cells
      have been demonstrated in human kidneys, requiring interpretation. This review
      presents some of the previous work and techniques and highlights issues that need
      to be reconciled. KEY MESSAGES: In adult humans, the kidney tubules contain
      scattered cells with a distinct set of markers and properties, such as increased
      robustness during tubular damage. These cells may be induced by injury or
      represent a resident progenitor cell pool. To date, animal studies using lineage
      tracing methods argue for an inductive scenario. In humans, the situation is less
      clear and one might speculate that the cellular heterogeneity might reflect
      elements of cellular reprogramming to a progenitor-like state, perhaps by
      induction. Due to intense investigational efforts, however, a scientific
      consensus may soon be reached, which will benefit further research.

PMID- 24854646
TI  - Restoring the function of a diseased kidney via its microvasculature.
AB  - BACKGROUND: Based upon observations which indicate that chronic intrarenal
      hypoxia and microvascular obliteration play an important role in the pathogenesis
      of renal scarring and loss of function, the idea is presented that restoration of
      kidney structure and function by arresting microvascular drop-out and restoring
      the interstitial capillary network could be a feasible approach to regeneration
      of a diseased kidney. This paper addresses the reasoning behind this possibility.
      SUMMARY: A 'unifying vasculogenic hypothesis' is discussed which proposes that,
      in hypoxic nephrons which retain poorly functioning vascular and epithelial
      elements, the disease process can be slowed or arrested, and nephrons
      regenerated, by adoptive transfer of endothelial progenitor cells to restore
      interstitial and glomerular vascular integrity. It is suggested that no other
      cell types are required to achieve this end. Improved differentiation,
      proliferation, and function of surviving nephrons could be achieved by restoring
      adequate oxygen delivery via this approach. KEY MESSAGES: It is hypothesized
      that, to regenerate the function of a chronically diseased kidney, it is not
      plausible to create new nephrons. Restoration of function of surviving nephrons
      could be achieved by regeneration of the renal microvasculature alone. Based upon
      observations that have demonstrated the feasibility of adoptive endothelial
      progenitor cell transfer into the kidney, this hypothesis is worthy of being
      tested.

PMID- 24854647
TI  - Can kidney regeneration be visualized?
AB  - BACKGROUND: Various cell types, including podocytes and parietal epithelial
      cells, play important roles in the development and progression of glomerular
      kidney diseases, albuminuria, and glomerulosclerosis. Besides their role in renal
      pathologies, glomerular cells have emerging new functions in endogenous repair
      mechanisms. A better understanding of the dynamics of the glomerular environment
      and cellular composition in an intact living kidney is critically important for
      the development of new regenerative therapeutic strategies for kidney diseases.
      However, progress in this field has been hampered by the lack of in vivo research
      tools. SUMMARY: This review summarizes the current state-of-the-art in the
      application of the unique intravital imaging technology of multiphoton
      fluorescence microscopy for the dynamic visualization of glomerular structure and
      function over time in the intact, living kidney. Recently, this imaging approach
      in combination with transgenic mouse models allowed tracking of the fate of
      individual glomerular cells in vivo over several days and depicted the highly
      dynamic nature of the glomerular environment, particularly in disease conditions.
      KEY MESSAGES: The technology is ready and available for future intravital imaging
      studies investigating new glomerular regenerative approaches in animal models.

PMID- 24854648
TI  - Drugs to foster kidney regeneration in experimental animals and humans.
AB  - BACKGROUND: The incidence of kidney diseases is increasing worldwide and they are
      emerging as a major public health problem. Once mostly considered inexorable,
      renal disease progression can now be halted and lesions can even regress with
      drugs such as angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II
      type I receptor blockers, indicating the possibility of kidney repair. SUMMARY:
      The discovery of renal progenitor cells lining the Bowman capsule of adult rat
      and human kidneys has shed light on the mechanism of repair by ACEi. Parietal
      progenitors are a reservoir of cells that contribute to podocyte turnover in
      physiological conditions. In the early phases of renal disease these progenitors
      migrate chaotically and subsequently proliferate, accumulating in Bowman's space.
      The abnormal behavior of parietal progenitors is sustained by the activation of
      CXCR4 receptors in response to an increased production of the chemokine SDF-1 by
      podocytes activated by the inflammatory environment. Ang II, via the AT1
      receptor, also contributes to progenitor cell proliferation. The CXCR4/SDF-1 and
      Ang II/AT1 receptor pathogenic pathways both pave the way for lesion formation
      and subsequent sclerosis. ACEi normalize the CXCR4 and AT1 receptor expression on
      progenitors, limiting their proliferation, concomitant with the regression of
      hyperplastic lesions in animals, and in a patient with crescentic glomerulopathy.
      KEY MESSAGE: Understanding the molecular and cellular determinants of
      regeneration triggered by renoprotective drugs will reveal novel pathways that
      might be challenged or targeted by pharmacological therapy.

PMID- 24854649
TI  - Role of parietal epithelial cells in kidney injury: the case of rapidly
      progressing glomerulonephritis and focal and segmental glomerulosclerosis.
AB  - BACKGROUND: Millions of people are affected by irreversible loss of renal
      function and thus by a significantly increased cardiovascular risk. In this
      context, the parietal epithelial cells (PECs) of the glomerulus have attracted
      increasing attention in recent years. So far, they have been ascribed 2 major
      functions: (1) PECs may act as intrinsic progenitor cells to replenish podocytes
      and/or proximal tubular cells and (2) a major role of PECs has been proposed in 2
      glomerular disease entities [i.e. rapidly progressing glomerulonephritis (RPGN)
      and focal and segmental glomerulosclerosis (FSGS)]. SUMMARY: In this review, the
      major recent findings regarding the role of PECs in glomerular disease are
      summarized. Novel transgenic technologies have allowed major advances, in
      particular cell fate-tracing studies. KEY MESSAGES: Using these methods, it could
      be established that the proliferating cells in Bowman's space, which are
      characteristically found in RPGN, are derived almost exclusively from the
      glomerular epithelium - primarily PECs. Similarly, it could be shown that PECs
      participate in the formation of sclerotic lesions in FSGS. Since PECs deposit
      their characteristic extracellular matrix within these lesions, they likely
      contribute to the sclerotic process. A common feature of both diseases is that
      PECs are 'activated', i.e. PECs acquire a larger cytoplasm and nucleus and show
      increased migration and/or proliferation. Activated PECs can be identified by de
      novo expression of the marker CD44. These findings broaden our understanding of
      the pathogenesis of 2 different glomerular diseases: RPGN and FSGS. The
      participation of activated PECs in both diseases identifies these cells as prime
      pharmacological targets to develop more specific therapies for both diseases.

PMID- 24854650
TI  - Cellular and developmental strategies aimed at kidney tissue engineering.
AB  - BACKGROUND: With the rate of kidney disease on the rise, and a serious imbalance
      between the number of patients requiring a kidney transplant and the number of
      available donor kidneys, it is becoming increasingly important to develop
      alternative strategies to restore organ function to diminish the need for human
      donors. SUMMARY: We review the current progress and future directions of a subset
      of these strategies which are ultimately aimed towards bioengineering a
      functional, implantable, kidney-like tissue construct or organoid that might be
      genetically matched to the patient. KEY MESSAGES: By combining the knowledge
      about normal kidney development with the rapidly growing knowledge in the field
      of cell differentiation and transdifferentiation, there is hope that partial or
      complete kidney function can be restored in patients with kidney disease -
      including genetic disorders, acute kidney injury, or chronic kidney disease -
      with tissue-engineered construct(s).

PMID- 24854651
TI  - Reforming the kidney starting from a single-cell suspension.
AB  - BACKGROUND: Chronic kidney disease affects 5-7% of people worldwide. The
      increasing number of patients and the shortage of transplantable organs create an
      imperative need to develop new methods for generating kidney tissue. SUMMARY:
      Recent advances in our understanding of the developmental biology of the kidney,
      along with the establishment of novel methodologies in the field of regenerative
      medicine, have created significant potential for kidney regeneration. These
      advances incorporate both transplantation of metanephric primordia into adult
      recipients and construction of 'fetal' kidney tissue from suspensions of single
      cells of metanephric origin. This paper examines these approaches in the context
      of organ regeneration. KEY MESSAGES: The use of transplants of metanephric origin
      has the advantage over undifferentiated stem cells of already being committed to
      a renal developmental program. Although several technical difficulties remain to
      be overcome, the validation of these systems in preclinical models of renal
      disease will be of decisive importance in the coming years.

PMID- 24854652
TI  - Renal bioengineering with scaffolds generated from rat and pig kidneys.
AB  - BACKGROUND: Chronic kidney disease (CKD) is a global public health issue with an
      estimated prevalence of 8-16% worldwide. End-stage renal disease eventually
      develops every year in 0.15-0.2% of patients with overt CKD, and renal
      replacement therapy (RRT) with dialysis or transplantation is required. Although
      approximately 2 million people worldwide are currently on RRT to sustain life,
      this likely represents less than 10% of those who need it. The kidney transplant
      approach is also seriously impaired by limited graft survival and by the scarce
      availability of donors. Innovative tissue-engineering strategies have been
      recently proposed to overcome these challenges. It is anticipated that these
      novel approaches will also be cost-effective in the long term. Although the
      initial setup of these innovative technologies could be quite expensive, there
      would be a single application for each patient, with no additional costs
      thereafter, compared to the lifelong costs of dialysis or immunosuppressive
      medications required for transplantation. One of the most innovative tools
      currently being investigated in experimental models is based on the idea of using
      decellularized kidneys to engineer a new functional organ as a potential future
      treatment option for end-stage renal disease. SUMMARY: In the last 5 years,
      several interesting observations have been reported regarding the possibility of
      using an acellular matrix from the whole kidney and the attempt to recellularize
      this scaffold using stem or differentiated cells. This review provides an
      overview of the decellularization methods tested so far and their effects on the
      resulting extracellular matrix structure and composition. In addition, we also
      discuss methods recently described by us and others for the perfusion of kidney
      scaffolds for recellularization. KEY MESSAGES: Despite difficulties in achieving
      the import goal of kidney engineering in the laboratory, we discuss the problems
      with and limits of the experimental results obtained so far and point out the
      strategies that need to be adopted in order for this line of research to advance.

PMID- 24854653
TI  - Renal bioengineering with scaffolds generated from human kidneys.
AB  - BACKGROUND: In 2012, about 16,487 people received kidney transplants in the USA
      whereas 95,022 candidates were on the waiting list at the end of the year.
      Moreover, more than 2,600 kidneys procured annually for transplantation are
      discarded for a variety of reasons. We hypothesize that this pool of discarded
      kidneys could in part meet the growing, urgent need for transplantable kidneys
      using current methods for organ bioengineering and regeneration and surgical
      transplantation. The recellularization of extracellular matrix (ECM) scaffolds
      has the potential to meet the uniquely ambitious engineering challenges posed by
      complex solid organs such as the kidney. SUMMARY: Attempts to manufacture and
      implant simpler, hollow structures such as bladders, vessels, urethras, and
      segments of the upper airways have been successful in the short and mid terms.
      However, the bioengineering of complex solid organs such as the kidney is a more
      challenging task that requires a different approach. In previous studies, we
      showed that decellularized porcine kidneys yield renal ECM scaffolds that
      preserve their basic architecture and structural components, support cell growth
      in vivo and in vitro, and maintain a patent vasculature capable of sustaining
      physiological blood pressure. In a subsequent report, using the same methods, we
      found that detergent-based decellularization of discarded human renal kidneys
      preserved their innate ECM framework, biochemical properties, and angiogenic
      capacity and - importantly - a patent vascular network. Furthermore, the process
      resulted in the clearance of immunogenic antigens, which has monumental
      implications for clinical outcomes in the long term in terms of graft rejection.
      Consequently, these kidneys show promise in bioengineering and transplantation.
      We refer to this avenue of research and development as 'cell-scaffold
      technology'. KEY MESSAGES: In 2011, more than 4,700 patients died while on the
      waiting list for a kidney transplant. In this context, we believe that cell
      scaffold technology has the potential to form a bridge between regenerative
      medicine and transplantation surgery. These methods, in theory, could provide a
      potentially inexhaustible source of transplantable organs. Unfortunately, current
      investigations are still in their very early stages and clinical translation is
      not immediately available in the short term. Thus, identifying the most important
      obstacles confronting cell-scaffold technology and focusing research efforts in
      this direction will be important for advancing the state of the art and meeting
      the clinical needs. We believe that cell-scaffold technology research and
      development would benefit greatly from a deeper understanding of the
      physiological mechanisms underlying the natural organogenesis, regeneration, and
      repair that characterize embryonic humans and simpler organisms. Furthermore, the
      importance of vascularization - the fundamental caveat of modern surgery - cannot
      be overstated, especially when discussing the implantation of de novo organs.

PMID- 24854654
TI  - Preoperative Gemcitabine-based Chemoradiation Therapy for Resectable and
      Borderline Resectable Pancreatic Cancer.

PMID- 24854655
TI  - Association study of polymorphisms between the Radixin gene and rheumatoid
      arthritis in a Korean population.
AB  - Radixin (RDX) is part of the ezrin-radixin-moesin (ERM) protein family. It
      functions as a membrane-cytoskeletal linker in actin-rich cell surface structures
      and is thought to be essential for cortical cytoskeleton organization, cell
      motility, adhesion, and proliferation. An increase in phosphorylated ERM in
      fibroblast-like synoviocytes contributes to rheumatoid arthritis (RA) synovial
      hyperplasia. We examined the genetic association between the RDX gene and RA in a
      Korean population. To identify the relationship between RDX gene polymorphisms
      and RA, we genotyped 2 single nucleotide polymorphisms (SNPs; rs11213326 and
      rs12575162) of RDX using a direct sequencing method in 296 RA patients and 493
      control subjects. In this study, the 2 SNPs showed no association with RA disease
      susceptibility. However, further analysis based on clinical information of the RA
      patient group showed that the SNPs were associated with the erythrocyte
      sedimentation rate (ESR) in RA patients. These data suggest an association
      between RDX polymorphisms and the clinical features of RA patients, particularly
      the ESR. 

PMID- 24854656
TI  - Expression of ERCC1 and BRCA1 predict the clinical outcome of non-small cell lung
      cancer in patients receiving platinum-based chemotherapy.
AB  - We examined mRNA expression levels of ERCC1, BRCA1, RRM1, and human beta-tubulin
      III (TUBB3) in non-small-cell lung carcinoma (NSCLC) patients and investigated
      the association between expression of these genes and the clinical outcome of
      NSCLC treatment. A total of 366 patients who underwent surgery for NSCLC were
      included in this study. All patients received third-generation platinum-based
      chemotherapy as first-line treatment. The relative cDNA quantification for ERCC1,
      RRM1, BRCA1, and TUBB3 was determined using a fluorescence-based, real-time
      detection method. We found that low expression of ERCC1 and BRCA1 was associated
      with a good response to platinum-based chemotherapy, with an odds ratio [95%
      confidence interval (CI)] of 2.09 (1.33-3.27) and 2.92 (1.85-4.62), respectively.
      Multivariate Cox regression analysis indicated that patients with low expression
      of ERCC1 and BRCA1 attained a longer overall survival time than those with high
      expression, with a hazard ratio (95%CI) of 0.42 (0.23-0.77) and 0.39 (0.21-0.71),
      respectively. However, RMM1 and TUBB2 expressions were not correlated with
      clinical outcome of NSCLC. In conclusion, we found that low expression of ERCC1
      and BRCA1 can be useful for selecting NSCLC patients who would benefit from
      chemotherapy and warrants further investigation in prospective studies. 

PMID- 24854657
TI  - Effects of Maytenus ilicifolia on reproduction and embryo-fetal development in
      Wistar rats.
AB  - Maytenus ilicifolia (Celastraceae), popularly known as espinheira-santa, is a
      native plant from the Atlantic forest and is commonly used in popular medicine to
      treat inflammation and as an abortifacient. To evaluate the effects of M.
      ilicifolia on pregnant rats during the organogenic period (T1) or throughout the
      gestational period (T2), an extract obtained using an acetone-water mixture at a
      70:30 ratio was administered via gavage at a dose of 15.11 mg.kg(-1).day(-1) over
      2 treatment periods (T1 and T2). No clinical signs of maternal toxicity were
      observed. Term fetuses did not present malformations or anomalies as the number
      of implantations, reabsorptions, live, and dead fetuses were similar to the
      control group. In conclusion, M. ilicifolia hydroacetonic extract is non-toxic to
      pregnant rats and appears to not interfere with the progress of embryo-fetal
      development. 

PMID- 24854658
TI  - Apoptotic effects of proteasome and histone deacetylase inhibitors in prostate
      cancer cell lines.
AB  - Prostate cancer is one of the most common types of urological cancers. Despite
      the implementation of effective radiotherapy and chemotherapy methods, prostate
      cancer cells can still show resistance to treatment. In recent years, a
      combination of proteasome and histone deacetylase inhibitors has been used to
      treat various malignancies. In this study, we examined the cytotoxic and
      apoptotic effects of the proteasome inhibitor bortezomib (Velcade/PS-341) and
      histone deacetylase inhibitor trichostatin A (TSA), used either alone or in
      combination, on the human prostate LNCaP and PC3 cell lines. We investigated the
      cytotoxic activity of these inhibitors using a WST-1 assay, IkBalpha and caspase
      3 mRNA levels by real-time polymerase chain reaction, and caspase-3 activity and
      activation of phosphorylated (p-IkBalpha) protein by Western blotting. Low-dose
      bortezomib and TSA synergistically induced apoptosis in both prostate cancer cell
      lines. Combination treatment with TSA with bortezomib effectively inactivated
      NFkB signaling, upregulated the predominant endogenous apoptotic factor caspase
      3, and disrupted the NFkB pathway in the androgen-independent PC3 cell line. In
      contrast, androgen-dependent LNCaP cells showed upregulation of caspase-3 through
      a pathway other than NFkB. This study examined the possible clinical use of
      bortezomib and TSA, together with reduced doses of chemotherapeutic agents with
      high cytotoxicity, to determine their apoptotic effects on the NFkB pathway in
      prostate cancer cell lines. Therefore, combination bortezomib and TSA treatment
      may represent a novel therapeutic strategy for prostate cancer. 

PMID- 24854659
TI  - Development of EST-SSR markers related to salt tolerance and their application in
      genetic diversity and evolution analysis in Gossypium.
AB  - Salt stress is becoming one of the major problems in global agriculture with the
      onset of global warming, an increasing scarcity of fresh water, and improper land
      irrigation and fertilization practices, which leads to reduction of crop output
      and even causes crop death. To speed up the exploitation of saline land, it is a
      good choice to grow plants with a high level of salt tolerance and economic
      benefits. As the leading fiber crop grown commercially worldwide, cotton is
      placed in the moderately salt-tolerant group of plant species, and there is
      promising potential to improve salt tolerance in cultivated cotton. To facilitate
      the mapping of salt-tolerant quantitative trait loci in cotton so as to serve the
      aims of salt-tolerant molecular breeding in cotton, it is necessary to develop
      salt-tolerant molecular markers. The objective of this research was to develop
      simple sequence repeat (SSR) markers based on cotton salt-tolerant expressed
      sequence tags. To test the efficacy of these SSR markers, their polymorphism and
      cross-species transferability were evaluated, and their value was further
      investigated on the basis of genetic diversity and evolution analysis. 

PMID- 24854660
TI  - Genome-wide identification and expression profiling of the fatty acid desaturase
      gene family in the silkworm, Bombyx mori.
AB  - Fatty acid desaturases exist in all living organisms and play important roles in
      many different biologic processes, such as fatty acid metabolism, lipid
      biosynthetic processes, and pheromone biosynthetic processes. Using the available
      silkworm genome sequence, we identified 14 candidate fatty acid desaturase genes.
      Eleven genes contain 3 conserved histidine cluster motifs and 4 transmembrane
      domains, but their N-terminal residues exhibit obvious diversity. Phylogenetic
      analysis revealed that there are 6 groups; Bmdesat1 and Bmdesat5-8 were clustered
      into group 2, which is involved in Delta11 desaturation activity, and Bmdesat3-4
      were grouped in group 1, which is involved in Delta9 desaturation activity.
      Twelve of the 14 genes have expressed sequence tag evidence. Microarray data and
      reverse transcription polymerase chain reaction analysis demonstrated that
      Bmdesat3-4 and Bmdesat10 were expressed from the larval to moth stages and in
      multiple tissues on day 3 of 5th instar larvae. Bmdesat9, Bmdesat11, and
      Bmdesat14 were expressed during the pupal and late-embryonic stage, suggesting
      that they may take part in fatty acid metabolism to provide energy. These results
      provide some insights into the functions of individual fatty acid desaturases in
      silkworm. 

PMID- 24854661
TI  - Comparative study between Ephedra sinica Stapf and Fructus Schisandrae Chinensis
      on ET-1 and 6-keto-prostaglandin F1alpha in rats with idiopathic pulmonary
      fibrosis.
AB  - The aim of this study was to evaluate differences in the effects of Ephedra
      sinica Stapf and Fructus Schisandrae Chinensis on angiogenesis in the treatment
      of bleomycin-induced rat idiopathic pulmonary fibrosis. The rat models were
      created using bleomycin. The animals were divided into six groups: model,
      control, Ephedra alone, Schisandrae alone, combination of Ephedra and
      Schisandrae, and hydrocortisone alone. The treatments were administered for 28
      days. After 7 and 28 days, the rats were sacrificed for pathological morphology
      examination, microvascular density determination, and angiogenesis-related
      cytokine examination. The Ephedra and hydrocortisone groups demonstrated
      significantly reduced alveolitis and pulmonary fibrosis grades compared with the
      model group (P < 0.05). The number of blood vessels in the Ephedra group was
      higher than that in the Schisandrae and combination therapy groups. At 7 days,
      the expression level of endothelin (ET)-1 in the model group was significantly
      higher than that in the normal group (P < 0.01). The level of 6-keto
      prostaglandin F1alpha (6-keto-PGF1alpha) in the treatment group increased, and
      there were significant differences between the Ephedra group and the combination
      therapy and normal groups (P < 0.05). Ephedra inhibited the increase in the lung
      coefficient. The combination therapy prevented pulmonary artery injury and
      angiogenesis of the arteries by reducing the level of ET-1 and promoting the
      level of 6-keto-PGF1alpha in the blood. Ephedra and Schisandrae prevented
      alveolitis and the development of pulmonary fibrosis. 

PMID- 24854662
TI  - Synaptic NF-kappa B pathway in neuronal plasticity and memory.
AB  - Several transcription factors are present at the synapse, and among these are the
      Rel-NF-kappa B pathway components. NF-kappa B is a constitutive transcription
      factor, with a strong presence in the brain of which a considerable part is
      located in the neuropiles. This localization of the transcription factor, plus
      evidence pointing to different functions, is what gave place to two general
      hypotheses for synaptic NF-kappa B: (a) The transcription factor plays a role in
      the synapse to nucleus communication, and it is retrogradely transported from
      polarized localizations to regulate gene expression; (b) The transcription factor
      modulates the synaptic function locally. Evidence indicates that both mechanisms
      can operate simultaneously; here we will present different possibilities of these
      hypotheses that are supported by an increasing amount of data. We pay special
      attention to the local role of the transcription factor at the synapse, and based
      in the described evidence from different animal models, we propose several
      processes in which the transcription factor may change the synaptic strength. 

PMID- 24854663
TI  - Boundary conditions for soft glassy flows: slippage and surface fluidization.
AB  - We explore the question of surface boundary conditions for the flow of a dense
      emulsion. We make use of microlithographic tools to create surfaces with well
      controlled roughness patterns and measure using dynamic confocal microscopy both
      the slip velocity and the shear rate close to the wall, which we relate to the
      notion of surface fluidization. Both slippage and wall fluidization depend non
      monotonously on the roughness. We interpret this behavior within a simple model
      in terms of the building of a stratified layer and the activation of plastic
      events by the surface roughness. 

PMID- 24854664
TI  - Predictors of sustained arteriovenous access use for haemodialysis.
AB  - BACKGROUND: Guidelines encourage early arteriovenous (AV) fistula (AVF) planning
      for haemodialysis (HD). The aim of this study was to estimate the likelihood of
      sustained AV access use taking into account age, sex, comorbidity, anatomical
      site of first AVF and, for pre-dialysis patients, eGFR and proteinuria. METHODS:
      1,092 patients attending our centre who had AVF as their first AV access
      procedure between January 1, 2000 and August 23, 2012 were identified from the
      electronic patient record. The primary end-point was time to first sustained AV
      access use, defined as use of any AV access for a minimum of 30 consecutive HD
      sessions. RESULTS: 52.9% (n = 578) of the patients ultimately achieved sustained
      AV access use. The main reasons for AV access non-use were AVF failure to mature
      and death. The 3-year Kaplan-Meier probability of sustained AV access use was
      68.8% for those not on renal replacement therapy (RRT) (n = 688) and 74.2% for
      those already on RRT (n = 404) at the time of first AVF. By multivariate analysis
      in patients not on RRT, male sex (HR 2.22; p < 0.001), uPCR (HR 1.03; p = 0.03)
      and eGFR (hazard ratio, HR 0.85; p < 0.001) were independent predictors of AV
      access use. In patients already on RRT, age (HR 0.98; p < 0.001) and peripheral
      vascular disease (HR 0.48; p = 0.02) were independent predictors of AV access
      use. CONCLUSION: Our data suggest that refinement of the current guideline for
      timing of AV access creation in planning RRT is justified to take into account
      individual factors that contribute to the likelihood of technical success and
      clinical need.

PMID- 24854665
TI  - Current bacterial speciation and antibiotic resistance in deep infections after
      operative fixation of fractures.
AB  - OBJECTIVES: Infection after fracture fixation is a major source of morbidity.
      Information regarding bacterial speciation and antibiotic resistance is lacking.
      We attempted to determine the speciation and drug resistance profiles associated
      with fracture fixation infections. DESIGN: Retrospective study. SETTING: Level I
      trauma center. PATIENTS: Two hundred eleven patients with 214 infections
      underwent surgery for postoperative infection from December 2006 to December
      2010. Deep postoperative infections within 12 months of fixation were included.
      INTERVENTION: None. MAIN OUTCOME MEASUREMENTS: Incidence of each bacterial
      species and rate of clinically relevant resistance in Staphylococcus aureus, gram
      negative rod (GNR), and Enterococcus species. The effect of timing of infection
      presentation and location of fracture on bacterial speciation was also
      investigated. RESULTS: Fifty-six percent of infections had S. aureus present,
      with 58% of those (32% of all infections) being methicillin-resistant S. aureus.
      Thirty-two percent of infections had at least one GNR present, with only 4% of
      those being multidrug resistant. We found a marked increase in the rate of GNR
      infections of the pelvis, acetabulum, and proximal femur (63%) compared with
      other locations (27%), which was statistically significant (P = 0.0002).
      CONCLUSIONS: At our center, S. aureus and GNR are most often found in deep
      postoperative infections after fixation. Methicillin-resistant S. aureus is
      common in this population. Our GNR rate is high, but resistance in this group was
      low. The proportion of GNR infections in the pelvis, acetabulum, and proximal
      femur was high even in closed fractures. These data provide a modern snapshot of
      orthopaedic infections after fracture fixation and might be useful in designing
      future studies and protocols for antibiotic prophylactic treatment. We are
      considering the use of aminoglycosides in the treatment of closed fractures of
      the pelvis, acetabulum, and proximal femur. LEVEL OF EVIDENCE: Prognostic Level
      IV. See Instructions for Authors for a complete description of levels of
      evidence.

PMID- 24854666
TI  - Lateral transmalleolar approach and miniscrews fixation for displaced
      posterolateral fragments of posterior malleolus fractures in adults: a
      consecutive study.
AB  - OBJECTIVES: To evaluate the lateral transmalleolar (LTM) approach for a displaced
      posterolateral fragments of a posterior malleolus fracture. DESIGN: Prospective,
      consecutive. SETTING: Level 1 trauma center. PATIENTS: Thirty-six patients.
      OUTCOME MEASURES: The x-rays, evaluation of arthritic changes of the ankle joint,
      range of motion, and Short Musculoskeletal Function Assessment questionnaire
      (SMFA). INTERVENTION: The LTM approach followed by multiple interfragmentary
      miniscrew-only fixation. RESULTS: No patients experienced intraoperative or
      postoperative complications that required a revision operation. All fractures
      healed. There were no infections, and no patient required implant removal. The
      median range of motion showed no significant difference as compared with the
      uninjured side. Patients achieved a mean SMFA dysfunction index of 8.2 +/- 2.4
      points and a mean SMFA bother index of 3.2 +/- 1.2 points. All patients performed
      normal daily life activities at averagely 3 (range, 2-5) months postoperatively.
      CONCLUSIONS: Direct visualization with the LTM approach followed by fixation with
      multiple miniscrews may be an alternative option for the treatment of ankle
      fractures with a posterolateral fragment associated with a posterior malleolar
      fracture. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors
      for a complete description of levels of evidence.

PMID- 24854668
TI  - Arthroscopic reduction and percutaneous fixation of selected calcaneus fractures:
      surgical technique and early results.
AB  - OBJECTIVES: To highlight a technique combining fluoroscopy and arthroscopy to aid
      percutaneous reduction and internal fixation of selected displaced intra
      articular calcaneal fractures, assess outcome scores, and compare this method
      with other previously reported percutaneous methods. DESIGN: Retrospective review
      of all patients treated by this technique between June 2009 and June 2012.
      SETTING: A tertiary care center located in Brisbane, Queensland, Australia.
      PATIENTS: Thirteen consecutive patients were treated by this method during this
      period. All patients had a minimum of 13 months follow-up and were available for
      radiological checks and assessment of complications; functional outcome scores
      were available for 9 patients. INTERVENTION: The patient was placed in a lateral
      decubitus position. Reduction was achieved with the aid of both intraoperative
      fluoroscopy and subtalar arthroscopy and held with cannulated screws in
      orthogonal planes. The patient was mobilized non-weight bearing for 10 weeks.
      MAIN OUTCOME MEASUREMENT: Outcomes measured were improvement in Bohler angle,
      postoperative complications, and 3 functional outcome scores (American
      Orthopaedic Foot and Ankle Society ankle-hindfoot score, Foot Function Index, and
      Calcaneal Fracture Scoring System). RESULTS: Mean postoperative improvement in
      Bohler angle was 18.3 degrees, with subsidence of 1.7 degrees. Functional outcome
      scores compared favorably with the prior literature. Based on available
      postoperative computed tomography scans (8/13), maximal residual articular
      incongruity measured 2 mm or less in 87.5% of our cases. CONCLUSIONS: Early
      results indicate that this technique, when combined with careful patient
      selection, offers a valid therapeutic option for the treatment of a distinct
      subset of displaced intra-articular calcaneal fractures, with diminished risk of
      wound complications. Large, prospective multicenter studies will be necessary to
      better evaluate the potential benefits of this technique. LEVEL OF EVIDENCE:
      Level IV Therapeutic. See Instructions for Authors for a complete description of
      levels of evidence.

PMID- 24854667
TI  - The management of pediatric subtrochanteric femur fractures with a statically
      locked intramedullary nail.
AB  - OBJECTIVES: To evaluate locked intramedullary (IM) fixation as an alternative
      treatment method for children with subtrochanteric fractures. DESIGN:
      Retrospective review. SETTING: Level 1 trauma center in a Children's Hospital.
      PATIENTS/PARTICIPANTS: Pediatric patients with subtrochanteric femur fractures
      with open growth plates. INTERVENTION: All patients were treated with a lateral
      entry IM locking nail. OUTCOME MEASUREMENTS: Patients were followed until full
      fracture consolidation or until implant removal. Data on time to full weight
      bearing, return to full activity, residual pain, any form of gait abnormality,
      and any other complication from follow-up visits were collected. RESULTS: There
      were 9 males and 1 female patient with an average age of 12 years and average
      follow-up of 22 months. Most of the fractures occurred secondary to high-energy
      trauma. Partial weight bearing was started at 24 days and full at 66 days.
      Implants were removed on average at 11 months after implantation. There were
      neither intraoperative complications nor major complications in the postoperative
      period recorded after removal. Two patients presented with a longer limb on the
      affected side, both 8 mm, and 2 presented with asymptomatic grade I heterotopic
      ossification. CONCLUSIONS: The use of a statically locked lateral entry IM nail
      for subtrochanteric femur fractures in children is a safe and efficacious method
      of treatment with few complications and risks and satisfactory outcomes in
      children over the age of 8 years. LEVEL OF EVIDENCE: Therapeutic Level IV. See
      Instructions for Authors for a complete description of levels of evidence.

PMID- 24854669
TI  - Psychometric properties of the Brazilian-Portuguese version of the Spence
      Children's Anxiety Scale (SCAS): self- and parent-report versions.
AB  - This study examined the psychometric properties of the Spence Children's Anxiety
      Scale (SCAS) self- and parent-report versions in a community (n=712) and a
      clinical (n=70) sample of Brazilian children and adolescents. Confirmatory factor
      analysis conducted in the community sample provided support to the original six
      correlated factors model of the SCAS. Moreover, the SCAS demonstrated good
      internal consistency, convergent and divergent validity, and a significant
      informant effect on the total score with higher anxiety levels in the self-report
      than in the parent-report version. Considering the clinical sample, we could
      demonstrate that the SCAS total scores have good discriminant validity
      differentiating: (a) anxious, community, and negative screening groups; and (b)
      children diagnosed with different severity levels of anxiety disorders. Our
      findings suggest that the SCAS (self- and parent-report versions) is suitable for
      assessing anxiety symptoms in Brazilian children and adolescents in community and
      clinical settings. 

PMID- 24854671
TI  - Midline forehead flap for reconstruction of cutaneous nasal defects.

PMID- 24854672
TI  - Enhancing the minimum data set for mass-gathering research and evaluation: an
      integrative literature review.
AB  - INTRODUCTION: In 2012, a minimum data set (MDS) was proposed to enable the
      standardized collection of biomedical data across various mass gatherings.
      However, the existing 2012 MDS could be enhanced to allow for its uptake and
      usability in the international context. The 2012 MDS is arguably Australian
      centric and not substantially informed by the literature. As such, an MDS with
      contributions from the literature and application in the international settings
      is required. METHODS: This research used an integrative literature review design.
      Manuscripts were collected using keyword searches from databases and journal
      content pages from 2003 through 2013. Data were analyzed and categorized using
      the existing 2012 MDS as a framework. RESULTS: In total, 19 manuscripts were
      identified that met the inclusion criteria. Variation in the patient presentation
      types was described in the literature from the mass-gathering papers reviewed.
      Patient presentation types identified in the literature review were compared to
      the 2012 MDS. As a result, 16 high-level patient presentation types were
      identified that were not included in the 2012 MDS. CONCLUSION: Adding patient
      presentation types to the 2012 MDS ensures that the collection of biomedical data
      for mass-gathering health research and evaluation remains contemporary and
      comprehensive. This review proposes the addition of 16 high-level patient
      presentation categories to the 2012 MDS in the following broad areas:
      gastrointestinal, obstetrics and gynecology, minor illness, mental health, and
      patient outcomes. Additionally, a section for self-treatment has been added,
      which was previously not included in the 2012 MDS, but was widely reported in the
      literature.

PMID- 24854670
TI  - Long-term outcomes of kidney transplantation across a positive complement
      dependent cytotoxicity crossmatch.
AB  - BACKGROUND: More than 30% of potential kidney transplant recipients have pre
      existing anti-human leukocyte antigen antibodies. This subgroup has significantly
      lower transplant rates and increased mortality. Desensitization has become an
      important tool to overcome this immunological barrier. However, limited data is
      available regarding long-term outcomes, in particular for the highest risk group
      with a positive complement-dependent cytotoxicity crossmatch (CDC XM) before
      desensitization. METHODS: Between 2002 and 2010, 39 patients underwent living
      kidney transplantation across a positive CDC XM against their donors at our
      center. The desensitization protocol involved pretransplant immunosuppression,
      plasmapheresis, and low-dose intravenous immunoglobulin+/-rituximab. Measured
      outcomes included patient survival, graft survival, renal function, rates of
      rejection, infection, and malignancy. RESULTS: The mean and median follow-up was
      5.2 years. Patient survival was 95% at 1 year, 95% at 3 years, and 86% at 5
      years. Death-censored graft survival was 94% at 1 year, 88% at 3 years, and 84%
      at 5 years. Uncensored graft survival was 87% at 1 year, 79% at 3 years, and 72%
      at 5 years. Twenty-four subjects (61%) developed acute antibody-mediated
      rejection of the allograft and one patient lost her graft because of hyperacute
      rejection. Infectious complications included pneumonia (17%), BK nephropathy
      (10%), and CMV disease (5%). Skin cancer was the most prevalent malignancy in 10%
      of patients. There were no cases of lymphoproliferative disorder. Mean serum
      creatinine was 1.7+/-1 mg/dL in functioning grafts at 5 years after
      transplantation. CONCLUSION: Despite high rates of early rejection,
      desensitization in living-kidney transplantation results in acceptable 5-year
      patient and graft survival rates.

PMID- 24854673
TI  - Decreased serum paraoxonase and arylesterase activities in patients with rosacea.
AB  - BACKGROUND: Recent evidence suggests that oxidative stress may be an important
      phenomenon in the pathophysiology of rosacea. Paraoxonase-1 (PON1) is an
      antioxidant enzyme with three activities: paraoxonase, arylesterase and
      dyazoxonase. In this study, we evaluated serum paraoxonase and arylesterase
      activities, and serum lipid hydroperoxide (LOOH) levels in patients with rosacea
      in comparison to healthy controls. MATERIAL AND METHOD: The study included 39
      rosacea patients and healthy controls, consisting of 40 age- and sex-matched
      healthy volunteers. Serum paraoxonase and arylesterase activities were measured
      using paraoxon and phenylacetate substrates. Serum LOOH levels were measured with
      the ferrous ion oxidation-xylenol orange assay. RESULTS: In rosacea group mean
      serum paraoxonase and arylesterase activities were 74.54 +/- 38.30 U L(-1) and
      141.29 +/- 22.27 kU L(-1) respectively, which were significantly lower than
      controls (P = 0.010, 0.005; respectively). Mean serum LOOH level of rosacea group
      was 8.17 +/- 1.91 MUmol L(-1) which was significantly higher than controls (P =
      0.009). There were no statistically significant differences between the clinical
      subtypes of the disease, menopause situation or ocular involvement with the
      respect to the serum paraoxonase and arylesterase activities and LOOH levels
      (all; P > 0.05). CONCLUSIONS: Serum PON1 enzyme activities have decreased
      significantly in rosacea. These findings support that decreased PON1 activity and
      increased oxidative stress may play a role in the pathogenesis of rosacea.
      Further studies are needed to elucidate the role of PON1 activity in the
      pathophysiology of rosacea.

PMID- 24854674
TI  - Improving cell adhesion: development of a biosensor for cell behaviour monitoring
      by surface grafting of sulfonic groups onto a thermoplastic polyurethane.
AB  - The surface properties of a material in combination with the mechanical
      properties are responsible for the material performance in a biological
      environment as well as the behaviour of the cells which contact with the
      material. Surface properties such as chemical, physical, biological play an
      important role in the biomaterials filed. In this work, the surface of a
      thermoplastic polyurethane film (Elastollan((r))1180A50) was tailored with
      sulfonic groups by grafting [2-(methacryloxyl)ethyl]-dimethyl-(3-sulfopropyl)
      ammonium hydroxide (SB) after a previous surface activation either by Argon
      plasma or by ultra-violet irradiation. This surface modification had the purpose
      of improving cell adhesion in order to develop a biosensor able to monitor cell
      behaviour. The surfaces were characterized by X-ray photoelectron spectroscopy,
      by atomic force microscopy and by contact angle measurements in order to evaluate
      the efficiency of the modification. Additionally, blood compatibility studies and
      cell adhesion tests with human bone marrow cells were performed. These methods
      allowed the grafting of SB and the results indicate that a higher density of
      grafting was achieved with previous surface plasma treatment than with UV
      irradiation. However, for both techniques, the presence of SB functional groups
      led to a decrease of hydrophobicity and roughness of the surface, together with
      an improvement of the materials biological performance. 

PMID- 24854675
TI  - Pairwise decomposition of an MMGBSA energy function for computational protein
      design.
AB  - Computational protein design (CPD) aims at predicting new proteins or modifying
      existing ones. The computational challenge is huge as it requires exploring an
      enormous sequence and conformation space. The difficulty can be reduced by
      considering a fixed backbone and a discrete set of sidechain conformations.
      Another common strategy consists in precalculating a pairwise energy matrix, from
      which the energy of any sequence/conformation can be quickly obtained. In this
      work, we examine the pairwise decomposition of protein MMGBSA energy functions
      from a general theoretical perspective, and an implementation proposed earlier
      for CPD. It includes a Generalized Born term, whose many-body character is
      overcome using an effective dielectric environment, and a Surface Area term, for
      which we present an improved pairwise decomposition. A detailed evaluation of the
      error introduced by the decomposition on the different energy components is
      performed. We show that the error remains reasonable, compared to other
      uncertainties.

PMID- 24854676
TI  - Olive leaf extract decreases age-induced oxidative stress in major organs of aged
      rats.
AB  - AIM: Olive leaf (Olea europaea L.) extract (OLE) is a powerful anti-oxidant rich
      in polyphenols. As oxidative stress plays an important role in aging, we
      investigated the effect of OLE on oxidative stress in the liver, heart and brain
      of aged rats. METHODS: Young (age 3 months) and aged (age 20 months) Wistar rats
      were used. Aged rats received OLE (500 and 1000 mg/kg/day) in drinking water for
      2 months. Malondialdehyde (MDA), diene conjugate (DC), protein carbonyl (PC),
      glutathione (GSH), vitamin E and vitamin C levels, and superoxide dismutase
      (SOD), glutathione peroxidase (GSH-Px) and glutathione transferase (GST)
      activities were determined. RESULTS: MDA, DC and PC levels increased in tissues
      of aged rats. GSH levels decreased in the liver, but not in the heart and brain.
      There was no change of other anti-oxidant parameters in tissues. Hepatic SOD and
      GSH-Px protein expressions also remained unchanged. OLE treatment caused
      decreased tissue MDA, DC and PC levels, and increased hepatic GSH levels in aged
      rats. Other anti-oxidant parameters, hepatic SOD and GSH-Px protein expressions
      did not alter in aged rats by OLE treatment. CONCLUSION: The present results
      suggest that OLE seems to be useful for decreasing oxidative stress in examined
      tissues by acting as an anti-oxidant itself without affecting the anti-oxidant
      system.

PMID- 24854677
TI  - National Academy of Sciences "standardization": on what terms?
AB  - The frequently cited 2009 National Academy of Sciences Report entitled
      "Strengthening Forensic Science in the United States: A Path Forward" has become
      a focal point of forensic science practitioners' discussions and research since
      its publication. One of its recommendations is "Standardized Terminology and
      Reporting". Little has been published to date on this topic, although
      conversations and dialogs on the subject are ongoing. The upshot of this
      communication is to draw attention to the problem of one term in particular,
      perimortem, which may be only the proverbial "tip of the iceberg" in the lexicon
      related concerns of forensic scientists. Even if it is an isolated issue, it is
      one that reflects the need for a consensus on term use and definitions by
      interdisciplinary practitioners who are currently using the term haphazardly, to
      the confusion of colleagues and potentially finders-of-fact in the courts. 

PMID- 24854678
TI  - Acidic preconditioning improves the proangiogenic responses of endothelial colony
      forming cells.
AB  - OBJECTIVE: Acidosis is present in several pathological conditions where
      vasculogenesis takes place including ischemia, tumor growth and wound healing. We
      have previously demonstrated that acidosis induces human CD34+ cell apoptosis.
      Considering that endothelial colony-forming cells (ECFC) are a subpopulation of
      CD34+ cells and key players in vasculogenesis, in the present study we
      investigated the effect of acidosis on the survival and functionality of ECFC.
      APPROACH AND RESULTS: Endothelial colony-forming cells obtained by
      differentiation of human cord blood CD34+ cells in endothelial growth medium-2
      for 14-21 days were exposed at pH 7.4, 7.0 or 6.6. We found that acidosis failed
      to induce ECFC apoptosis and, although an early reduction in proliferation,
      chemotaxis, wound healing and capillary-like tubule formation was observed, once
      the medium pH was restored to 7.4, ECFC proliferation and tubulogenesis were
      augmented. Stromal cell derived factor-1 (SDF1)-driven migration and chemokine
      receptor type 4 surface expression were also increased. The maximal proangiogenic
      effect exerted by acidic preconditioning was observed after 6 h at pH 6.6.
      Furthermore, preconditioned ECFC showed an increased ability to promote tissue
      revascularization in a murine model of hind limb ischemia. Immunoblotting assays
      showed that acidosis activated AKT and ERK1/2 and inhibited p38 pathways.
      Proliferation rises triggered by acidic preconditioning were no longer observed
      after AKT or ERK1/2 inhibition, whereas p38 suppression not only mimicked but
      also potentiated the effect of acidosis on ECFC tubule formation abilities.
      CONCLUSIONS: These results demonstrate that acidic preconditioning greatly
      increases ECFC-mediated angiogenesis in vitro including ECFC proliferation,
      tubulogenesis and SDF1-driven chemotaxis and is a positive regulator of
      microvessel formation in vivo.

PMID- 24854679
TI  - Fine structure of Delia platura (Meigen) (Diptera: Anthomyiidae) revealed by
      scanning electron microscopy.
AB  - Delia platura (Meigen) is a phytophagous fly that can cause significant crop
      losses. To obtain a better understanding of the external morphology of this
      species, adult D. platura is studied using scanning electron microscopy. Organs
      or structures that are important for taxonomy, such as the compound eyes,
      spiracles, pulvilli, wings, and genitalia are highlighted to complement previous
      description based on light microscope. Mesothoracic and metathoracic spiracles of
      D. platura that provide efficiency in preventing entrance of fine materials or
      dust into the tracheal system are morphologically different. In addition, the
      elongate-oval pulvillus is densely covered with tenent setae with spoon-like tip,
      which can increase the number of contact points for attachment to a surface. Four
      types of sensilla are observed on the male genitalia of D. platura including:
      trichoid sensilla, chaetic sensilla, three subtypes of campaniform sensilla, and
      basiconic sensilla. Long bristles and microtrichiae are observed on the female
      genitalia of D. platura. The possible function of sensilla located in the
      genitalia of D. platura is discussed. Microsc. Res. Tech. 77:619-630, 2014. (c)
      2014 Wiley Periodicals, Inc. 

PMID- 24854681
TI  - Laboratory diagnostic tools for personalized fetal medicine and improving
      neonatal outcomes.

PMID- 24854682
TI  - High grade osteosarcoma. Clinico-pathological aspects and molecular prognostic
      factors.

PMID- 24854683
TI  - The impact of therapeutic drug monitoring in neonatal clinical pharmacology.

PMID- 24854684
TI  - Novel biomarkers for diagnosing and understanding pathophysiology of metabolic
      diseases.

PMID- 24854685
TI  - KiGGS - the German survey on children's health as data base for reference
      intervals and beyond.

PMID- 24854686
TI  - Pediatric clinical chemistry: why is it different?

PMID- 24854680
TI  - Comparison of cellular architecture, axonal growth, and blood vessel formation
      through cell-loaded polymer scaffolds in the transected rat spinal cord.
AB  - The use of multichannel polymer scaffolds in a complete spinal cord transection
      injury serves as a deconstructed model that allows for control of individual
      variables and direct observation of their effects on regeneration. In this study,
      scaffolds fabricated from positively charged oligo[poly(ethylene glycol)fumarate]
      (OPF(+)) hydrogel were implanted into rat spinal cords following T9 complete
      transection. OPF(+) scaffold channels were loaded with either syngeneic Schwann
      cells or mesenchymal stem cells derived from enhanced green fluorescent protein
      transgenic rats (eGFP-MSCs). Control scaffolds contained extracellular matrix
      only. The capacity of each scaffold type to influence the architecture of
      regenerated tissue after 4 weeks was examined by detailed immunohistochemistry
      and stereology. Astrocytosis was observed in a circumferential peripheral channel
      compartment. A structurally separate channel core contained scattered astrocytes,
      eGFP-MSCs, blood vessels, and regenerating axons. Cells double-staining with
      glial fibrillary acid protein (GFAP) and S-100 antibodies populated each scaffold
      type, demonstrating migration of an immature cell phenotype into the scaffold
      from the animal. eGFP-MSCs were distributed in close association with blood
      vessels. Axon regeneration was augmented by Schwann cell implantation, while eGFP
      MSCs did not support axon growth. Methods of unbiased stereology provided
      physiologic estimates of blood vessel volume, length and surface area, mean
      vessel diameter, and cross-sectional area in each scaffold type. Schwann cell
      scaffolds had high numbers of small, densely packed vessels within the channels.
      eGFP-MSC scaffolds contained fewer, larger vessels. There was a positive linear
      correlation between axon counts and vessel length density, surface density, and
      volume fraction. Increased axon number also correlated with decreasing vessel
      diameter, implicating the importance of blood flow rate. Radial diffusion
      distances in vessels significantly correlated to axon number as a hyperbolic
      function, showing a need to engineer high numbers of small vessels in parallel to
      improving axonal densities. In conclusion, Schwann cells and eGFP-MSCs influenced
      the regenerating microenvironment with lasting effect on axonal and blood vessel
      growth. OPF(+) scaffolds in a complete transection model allowed for a detailed
      comparative, histologic analysis of the cellular architecture in response to each
      cell type and provided insight into physiologic characteristics that may support
      axon regeneration. 

PMID- 24854687
TI  - Novel approach for Newborn Errors in Metabolism Screening (NEMS) by NMR: clinical
      NEMS-by-NMR study in Turkey.

PMID- 24854688
TI  - Current issues in diagnostic allergy testing in children for a group of
      laboratorians.

PMID- 24854689
TI  - Clinical relevance of AFP, its molecular variants and HCG in hepatoblastoma and
      childhood germ cell tumors.

PMID- 24854690
TI  - The development of type 2 diabetes in the obese adolescents: a growing challenge.

PMID- 24854691
TI  - Cardiovascular risk prediction in children and adolescents.

PMID- 24854692
TI  - New therapeutic principles for Familial Hypercholesterolemia.

PMID- 24854693
TI  - Neonatal hypoglycemia.

PMID- 24854694
TI  - Non-alcoholic fatty liver disease in children and adolescents.

PMID- 24854695
TI  - Biomarkers in pediatric tumors.

PMID- 24854696
TI  - Hormone profiles in extremely preterm infants.

PMID- 24854697
TI  - What to expect from a bilirubin analysis for management of jaundiced newborns?

PMID- 24854698
TI  - Novel diagnostic options for immunodeficiencies.

PMID- 24854700
TI  - Delivering safe and effective parenteral nutrition.

PMID- 24854699
TI  - Diagnosis of neonatal sepsis: what the clinician expects, what the laboratory
      tells.

PMID- 24854701
TI  - In-vitro diagnosis of allergic diseases.

PMID- 24854702
TI  - Ammonia, a troublesome analyte.

PMID- 24854703
TI  - Screening of priority pesticides in Ulva sp. seaweeds by selective pressurized
      solvent extraction before gas chromatography with electron capture detector
      analysis.
AB  - This work reports a fast and reliable analytical method for the screening of
      priority pesticides (PPs) in Ulva sp. seaweeds by gas chromatography with
      electron capture detection. Extraction and sample clean-up were performed in one
      single step by selective pressurized liquid extraction (SPLE). Several parameters
      affecting SPLE performance were optimized. Method performance was compared with
      standard Soxhlet extraction. Significant decrease of the time of analysis with
      better recoveries for a greater number of PPs was achieved by SPLE. Average
      recoveries ranged from 71 to 103% with RSD < 10%. Field application showed the
      presence of PP in the range of 3-11 ng g(-1) in seaweeds collected in a coastal
      lagoon after a long period of heavy rains. These results suggest that Ulva sp.
      seaweeds tend to accumulate PPs and have the potential to be used as early alert
      signals of aquatic pollution especially after rains and storm events.

PMID- 24854704
TI  - Assessment of lead exposure in waterfowl species, Korea.
AB  - Lead concentrations were analyzed in white-fronted geese (Anser albifrons, n =
      15), mallards (Anas platyrhynchos, n = 4), and spot-billed ducks (A.
      poecilorhyncha, n = 13) found dead near Gimpo, Korea, to determine tissue- and
      species-specific lead concentration differences and to assess the effect of
      embedded lead shot. In livers, kidneys, and bones (tarsus), mallards and spot
      billed ducks with embedded shot had greater lead concentrations than white
      fronted geese and spot-billed ducks without lead shot. Lead concentrations in
      spot-billed ducks were greater in bones than in livers and kidneys suggesting
      chronic exposure to lead. Lead concentrations in 8 of 32 livers, 5 of 32 kidneys,
      and 9 of 32 bones exceeded the threshold level of abnormal exposure for wild
      birds (>5 ug/g dw in lives, >6 ug/g dw in kidney, and >6.75 ug/g dw in bone).
      Increased lead concentrations in soft tissues and bones might be attributed to
      increased lead shot ingestion and embedded shot. Lead concentrations were
      correlated between livers and kidneys, between livers and bones, and between
      kidneys and bones. These results suggest that a relationship between acute
      exposure in livers and kidneys and chronic exposure in bones.

PMID- 24854705
TI  - In vitro effects of selenium on copper-induced changes in lipid metabolism of
      grass carp (Ctenopharyngodon idellus) hepatocytes.
AB  - The present study was performed to evaluate the in vitro effects of selenium (Se)
      supplementation to prevent copper (Cu)-induced changes in lipid metabolism of
      hepatocytes from grass carp (Ctenopharyngodon idellus). Four groups (control and
      100 MUM Cu in combination with 0, 5, and 10 MUM Se, respectively) were chosen.
      Compared with the control, activities of glucose 6-phosphatedehydrogenase, 6
      phosphogluconate dehydrogenase, malic enzyme, and carnitine palmitoyltransferase
      I (CPT I) of all three Cu-exposed groups at 24 and 48 h were significantly
      greater. However, among three Cu-exposed groups, increasing Se concentration
      tended to increase activities of G6PD and ME at 24 h and 6PGD activity at 24 and
      48 h but decreased CPT I activity at 24 h. Compared with the control, Cu exposure
      alone, or in combination with Se, downregulated mRNA levels of sterol regulatory
      element-binding protein-1 (SREBP-1c), fatty acid synthase (FAS), acetyl-CoA
      carboxylase, peroxisome proliferator activated receptor alpha (PPARalpha), CPT I,
      and hormone-sensitive lipase (HSL) at 24 h as well as SREBP-1c, FAS, and ACC mRNA
      levels at 48 h. However, upregulated mRNA levels of PPARalpha, CPT I, and HSL, as
      well as decreased triglyceride content, were recorded at 48 h. Thus, although
      toxic at greater levels, lower levels of Se provided significant protection
      against Cu-induced changes in lipid metabolism. For the first time, our study
      indicates the dose- and time-dependent effects of Se addition on changes in lipid
      metabolism induced by Cu in fish hepatocytes and provides new insights into Se-Cu
      interaction at both enzymatic and molecular levels.

PMID- 24854707
TI  - Characteristics of an organic solvent-tolerant beta-fructofuranosidase from
      Arthrobacter arilaitensis NJEM01 and efficient synthesis of prebiotic kestose.
AB  - An organic solvent-tolerant beta-fructofuranosidase (beta-FFase) from
      Arthrobacter arilaitensis NJEM01 was purified, characterized, cloned, and
      overexpressed in Escherichia coli. The mature beta-FFase contained 495 amino acid
      residues with an estimated molecular mass of 55 kDa. The purified beta-FFase from
      strain NJEM01 was very stable in the buffer systems (pH 5.0-9.5) and showed high
      stability below 45  degrees C. Furthermore, the enzyme exhibited relatively high
      solvent stability in various aqueous organic mixtures and retained nearly 100% of
      its initial activity after incubation for 10 days in 20% (v/v) DMSO. In addition,
      the beta-FFase exhibited high transfructosylation activity, synthesized prebiotic
      products of mainly 6-kestose (up to 476 g/L), and showed fructosyl receptor
      specificity to C-glucosyl flavone. A relatively high yield of FOS was achieved by
      the beta-FFase from bacterium with a high concentration of sucrose. It made the
      beta-FFase an exploitable biocatalyst for the production of glycosides of natural
      products and prebiotic kestose. 

PMID- 24854708
TI  - Aminophenylboronic-acid-conjugated polyacrylic acid-Mn-doped ZnS quantum dot for
      highly sensitive discrimination of glycoproteins.
AB  - Discrimination of glycoproteins with different glycans is a significant but
      difficult issue. We presented here a new strategy for strengthening the
      discrimination of glycoproteins by introducing a new signaling channel,
      fluorescence polarization (FP), into a "single probe with three signaling
      channels" sensor array. The single probe was aminophenylboronic-acid-conjugated
      poly(acrylic acid)-Mn-doped ZnS quantum dots, and the three signaling channels
      were FP, room temperature phosphorescence and light scattering. Ten
      glycoproteins, including ovalbumin, fibrinogen, transferrin, horseradish
      peroxidase, vascular endothelial growth factor, immunoglobulin G, avidin,
      hyaluronidase, cellulase R-10, and glucose oxidase, were involved for evaluating
      the discriminating capability. The introduction of the FP signaling channel
      improved the discriminating power of the sensor array, so that the 10
      glycoproteins at 0.15 MUM could be well discriminated both in PBS buffer and in
      the presence of human serum sample. The identification accuracy of the unknown
      samples was 96.25% (77 out of 80) at the 0.15 MUM level and 97.50% (78 out of 80)
      at the 0.2 MUM level. The integration of the signaling patterns with different
      responsive principles was demonstrated as the promising way to enhance the
      discrimination power of the single-probe-based sensor arrays. 

PMID- 24854706
TI  - Angiotensin IV is induced in experimental autoimmune encephalomyelitis but fails
      to influence the disease.
AB  - In multiple sclerosis (MS) and its corresponding animal models, over-activity of
      the renin-angiotensin system (RAS) has been reported and pharmacological RAS
      blockade exerts beneficial effects. The RAS generates a number of bioactive
      angiotensins, thereby primarily regulating the body's sodium homeostasis and
      blood pressure. In this regard, angiotensin IV (AngIV), a metabolite of the RAS
      has been shown to modulate inflammatory responses. Here we studied potential
      implications of AngIV signalling in myelin oligodendrocyte glycoprotein (MOG)
      peptide induced murine experimental autoimmune encephalomyelitis (EAE), a close
      to-MS animal model. Mass spectrometry revealed elevated plasma levels of AngIV in
      EAE. Expression of cognate AT4 receptors was detected in macrophages and T cells
      as major drivers of pathology in EAE. Yet, AngIV did not modulate macrophage or T
      cell functions in vitro or displayed detectable effects on neuroantigen specific
      immune responses in vivo. The data argue against a major contribution of AngIV
      signalling in the immunopathogenesis of MOG-EAE. 

PMID- 24854709
TI  - Ionic liquid-based aqueous two-phase system extraction of sulfonamides in milk.
AB  - A simple method for the determination of six sulfonamides (SAs) in milk samples
      was developed. 1-Butyl-3-methylimidazolium tetrafluoroborate and trisodium
      citrate dihydrate were used to form aqueous two-phase system. The aqueous two
      phase system was applied to the extraction of the SAs and the determination of
      the analytes was performed by high-performance liquid chromatography. To achieve
      optimum extraction performance, several experimental parameters, including the
      type and the amount of salt, the type and amount of ionic liquid, ultrasonic time
      and pH of sample solution, were investigated and optimized. Under the optimal
      experimental conditions, good linearity was observed in the range of 8.55
      1036.36ngmL(-1). The limits of detection and quantification were in the range of
      2.04-2.84 and 6.73-9.37ngmL(-1), respectively. The present method was
      successfully applied to the determination of SAs in milk samples, and the
      recoveries of analytes were in the range of 72.32-108.96% with relative standard
      deviations ranging from 0.56 to 12.20%. The results showed that the present
      method was rapid, feasible and environmentally friendly. 

PMID- 24854710
TI  - High performance liquid chromatography-tandem mass spectrometric assay of
      dexmedetomidine in plasma, urine and amniotic fluid samples for pregnant ewe
      model.
AB  - Dexmedetomidine (DEX; Precedex((r))), approved by the Food and Drug
      Administration (FDA) in 1999 as a sedative for use in the intensive care unit, is
      a potent and highly selective alpha2-adrenoceptor agonist with significant
      sedative, analgesic and anxiolytic effects. However, the research of DEX use
      during pregnancy is limited and the impact of DEX on the fetal development is
      unclear. This article describes a high performance liquid chromatography-tandem
      mass spectrometry (HPLC-MS/MS) assay suitable for various biomatrices of plasma,
      urine and amniotic fluid, as a prerequisite for pharmacokinetic characterization
      of DEX in the pregnant ewe model. DEX and testosterone (internal standard; IS)
      were extracted from 200MUL of plasma, urine or amniotic fluid with ethyl acetate.
      The HPLC resolution was achieved on an Agilent ZORBAX SB-CN column with a
      gradient elution at a flow rate of 0.5mL/min using a mobile phase of 5-100% of
      acetonitrile with 0.5% formic acid (mobile phase B) in water (mobile phase A).
      The detection was performed by a triple quadrupole tandem mass spectrometer with
      positive electrospray ionization. The precursor/product transitions (m/z) in the
      positive ion mode [M+H](+) were m/z 201.5->95.4 for DEX and m/z 289.2->109.1 for
      IS. The method was validated in the concentration range of 25 (lower limit of
      quantification; LLOQ)-5000pg/mL for both maternal and fetal plasma, and of 50
      (LLOQ)-5000pg/mL for urine and amniotic fluid, respectively. The intra- and inter
      day precision and accuracy were within +/-9%. The overall recoveries of DEX were
      82.9-87.2%, 85.7-88.4%, 86.2-89.7% and 83.7-88.1% for maternal plasma, urine,
      fetal plasma and amniotic fluid, respectively. The percentage matrix factors in
      different biomatrices were less than 120%. Stability studies demonstrated that
      DEX was stable after three freeze/thaw cycles, in the autosampler tray at 20
      degrees C for 24h and during the 3h sample preparation at room temperature. The
      validated HPLC-MS/MS method has been successfully employed for pharmacokinetic
      evaluation of DEX in pregnant ewes and fetuses. 

PMID- 24854711
TI  - A sensitive liquid chromatography-tandem mass spectrometry method for
      pharmacokinetics and tissue distribution of nuciferine in rats.
AB  - Nuciferine is an important drug candidate for the treatment of obesity-related
      diseases. However, few investigations have been conducted about the
      pharmacokinetics and tissue distribution of nuciferine to better understand its
      behavior and action mechanism in vivo. Thus, a sensitive and reliable liquid
      chromatography with tandem mass spectrometry (HPLC-MS/MS) method was established
      and validated for the quantification of nuciferine in rat plasma and tissue
      samples. The validated method was successfully applied to the pharmacokinetic and
      tissue distribution study of nuciferine in rats. One-compartmental
      pharmacokinetic parameters indicated that nuciferine had rapid distribution,
      extensive tissue uptake, and poor absorption into systemic circulation. The
      values of absolute bioavailability were (3.8+/-1.4)%, (4.2+/-1.3)% and (3.9+/
      1.0)% after oral administration of 2.0, 5.0 and 10.0mg/kg nuciferine and
      intravenous administration of 0.2mg/kg nuciferine in rats. The results of the
      tissue distribution study suggested that nuciferine was distributed into the
      brain, liver and adipose tissue after intravenous administration. In conclusion,
      the present study may provide a material basis for study of the pharmacological
      action of nuciferine in the treatment of obesity, and meaningful insights into
      further study on dosage modification. 

PMID- 24854712
TI  - Validity and reliability of instruments aimed at measuring Evidence-Based
      Practice in Physical Therapy: a systematic review of the literature.
AB  - RATIONALE, AIMS AND OBJECTIVES: Our goal is to compile and analyse the
      characteristics - especially validity and reliability - of all the existing
      international tools that have been used to measure evidence-based clinical
      practice in physiotherapy. METHODS: A systematic review conducted with data from
      exclusively quantitative-type studies synthesized in narrative format. An in
      depth search of the literature was conducted in two phases: initial, structured,
      electronic search of databases and also journals with summarized evidence;
      followed by a residual-directed search in the bibliographical references of the
      main articles found in the primary search procedure. The studies included were
      assigned to members of the research team who acted as peer reviewers. Relevant
      information was extracted from each of the selected articles using a template
      that included the general characteristics of the instrument as well as an
      analysis of the quality of the validation processes carried out, by following the
      criteria of Terwee. RESULTS: Twenty-four instruments were found to comply with
      the review screening criteria; however, in all cases, they were found to be
      limited as regards the 'constructs' included. Besides, they can all be seen to be
      lacking as regards comprehensiveness associated to the validation process of the
      psychometric tests used. CONCLUSION: It seems that what constitutes a rigorously
      developed assessment instrument for EBP in physical therapy continues to be a
      challenge.

PMID- 24854713
TI  - Overexpression of the maize GRF10, an endogenous truncated growth-regulating
      factor protein, leads to reduction in leaf size and plant height.
AB  - It has long been thought that growth-regulating factors (GRFs) gene family
      members act as transcriptional activators to play important roles in multiple
      plant developmental processes. However, the recent characterization of
      Arabidopsis GRF7 showed that it functions as a transcriptional repressor of
      osmotic stress-responsive genes. This highlights the complex and diverse
      mechanisms by which different GRF members use to take action. In this study, the
      maize (Zea mays L.) GRF10 was functionally characterized to improve this concept.
      The deduced ZmGRF10 protein retains the N-terminal QLQ and WRC domains, the
      characteristic regions as protein-interacting and DNA-binding domains,
      respectively. However, it lacks nearly the entire C-terminal domain, the regions
      executing transactivation activity. Consistently, ZmGRF10 protein maintains the
      ability to interact with GRF-interacting factors (GIFs) proteins, but lacks
      transactivation activity. Overexpression of ZmGRF10 in maize led to a reduction
      in leaf size and plant height through decreasing cell proliferation, whereas the
      yield-related traits were not affected. Transcriptome analysis revealed that
      multiple biological pathways were affected by ZmGRF10 overexpression, including a
      few transcriptional regulatory genes, which have been demonstrated to have
      important roles in controlling plant growth and development. We propose that
      ZmGRF10 aids in fine-tuning the homeostasis of the GRF-GIF complex in the
      regulation of cell proliferation. 

PMID- 24854714
TI  - Effect of a new combined therapy with nano-carbonate apatite and CO2 laser on
      dentin hypersensitivity in an in situ model.
AB  - OBJECTIVE: The aim of this study was to determine the occluding effects of a
      combination of dentifrice containing nano-carbonate apatite (n-CAP) and CO2 laser
      on dentinal tubules, and to evaluate the acid resistance of this combination
      after 4 days of treatment, by using an in situ model. BACKGROUND DATA: The
      synergic effect of this combination was demonstrated in an in vitro study.
      METHODS: This was a two period crossover, single-blind, randomized, four
      treatment, split-mouth study. Ten healthy participants wore lower intraoral
      appliances during the treatment period. Specimens were divided into the following
      four groups: no treatment (control group), tooth-brushing using 20% n-CAP
      dentifrice (n-CAP group), CO2 laser irradiation (laser group), and laser
      irradiation after n-CAP application (combined group). Occluding effects were
      evaluated on 2 days (days 1 and 2), and then acid challenge was performed using
      grape juice on 2 days (days 3 and 4). All of the specimen surfaces were evaluated
      by a scanning electron microscope. RESULTS: The combined group showed a better
      occluding effect than control group compared with other treatment groups, and
      this effect was 20% higher than that in the n-CAP group. Also, the combined group
      had the smallest open dentinal tubular area among all of the treatment groups.
      CONCLUSIONS: The combined therapy is a promising method for ensuring a long
      lasting effect of dentin hypersensitivity treatment in clinical practice.

PMID- 24854722
TI  - Cytosine unstacking and strand slippage at an insertion-deletion mutation
      sequence in an overhang-containing DNA duplex.
AB  - Base unstacking in template strands, when accompanied by strand slippage, can
      result in deletion mutations during strand extension by nucleic acid polymerases.
      In a GCCC mutation hot-spot sequence, which was previously identified to have a
      50% probability of causing such mutations during DNA replication by a Y-family
      polymerase, a single-base deletion mutation could result from such unstacking of
      any one of its three template cytosines. In this study, the intrinsic energetic
      differences in unstacking among these three cytosines in a solvated DNA duplex
      overhang model were examined using umbrella sampling molecular dynamics
      simulations. The free energy profiles obtained show that cytosine unstacking
      grows progressively more unfavorable as one moves inside the duplex from the 5'
      end of the overhang template strand. Spontaneous strand slippage occurs in
      response to such base unstacking in the direction of both the major and minor
      grooves for all three cytosines. Unrestrained simulations run from three distinct
      strand-slipped states and one non-strand-slipped state suggest that a more
      duplexlike environment can help stabilize strand slippage. The possible
      underlying reasons and biological implications of these observations are
      discussed in the context of nucleic acid replication active site dynamics.

PMID- 24854723
TI  - Abnormal cortical activation in females with acute migraine: a
      magnetoencephalography study.
AB  - OBJECTIVE: The objective of this study was to investigate functional
      abnormalities of the brain in females with migraine using magnetoencephalography
      (MEG) and a finger-tapping task. METHODS: Twenty-nine female patients with
      migraine (aged 16-40years) and age- and gender-matched healthy controls were
      studied with an MEG system at a sampling rate of 6000Hz. MEG recordings were
      performed during an attack in migraineurs with and without aura. Neuromagnetic
      brain activation was elicited by a finger-tapping task. The latency and amplitude
      of neuromagnetic responses were analyzed with averaged waveforms in the frequency
      range of 5-100Hz. The Morlet wavelet and beamformers were used to analyze the
      spectral and spatial signatures of MEG data from subjects in two frequency ranges
      of 5-100 and 100-1000Hz. RESULTS: The latency of motor-evoked magnetic fields
      evoked by finger movement was significantly prolonged in migraineurs as compared
      with controls. Neuromagnetic spectral power in the motor cortex in migraineurs
      was significantly elevated. There were significantly higher odds of activation in
      5-30, 100-300 and 500-700Hz frequency ranges in the ipsilateral primary motor
      cortices and the supplementary motor area in migraineurs as compared with
      controls. CONCLUSIONS: Neuromagnetic signal abnormalities in this study suggest
      cortical hyperexcitability in females with migraine during migraine attack, which
      could be measured and analyzed with MEG signal in a frequency range of 5-1000Hz.
      SIGNIFICANCE: These findings may help to identify neurophysiological biomarkers
      for studying mechanisms of migraine, and may facilitate to develop new
      therapeutic strategies for migraine by alterations in cortical excitability.

PMID- 24854724
TI  - [Neurological soft signs in early onset schizophrenia].
AB  - INTRODUCTION: Neurological soft signs (NSS) are subtle neurological abnormalities
      that cannot be linked to the achievement of a specific region of the central
      nervous system and which are not part of a particular neurological syndrome.
      These signs are observed in the case of diseases supporting the
      neurodevelopmental model such as schizophrenia in general and its early form
      defined notably by an age of onset of less than 18 years. Indeed, the NSS belong
      to a set of clinical, cognitive, electrophysiological and neuroanatomical markers
      reflecting neurodevelopmental brain abnormalities in patients with schizophrenia.
      OBJECTIVE: The objectives of our study were to determine the prevalence, the
      scores, and the nature of neurological soft signs (NSS) in adolescent patients
      suffering from early onset schizophrenia diagnosis in comparison to healthy
      controls, and to explore the correlations between NSS and the demographic,
      clinical and therapeutic features of these patients. MATERIALS AND METHODS:
      Twelve adolescents were recruited in the Child Psychiatry Department at the Razi
      Hospital (Tunisia), with the diagnosis of schizophrenia according to the DSM-IV
      supplemented by the Kiddie SAD PL. They were matched by age and educational level
      with twelve healthy controls without psychiatric family or personal history. The
      clinical status of the patients was assessed using the Positive and Negative
      Syndrome Scale (PANSS). Neurological soft signs (NSS) were rated with the
      Neurological Soft Signs Examination (NSSE) by Krebs et al. (2000) for the two
      groups. This scale is composed of 23 items exploring motor coordination, motor
      integrative function, sensory integration, involuntary movements and quality of
      lateralization. RESULTS: The mean age of our population was 14.7 years. The
      average age of onset of the disease was 12.2 years. The sex-ratio was 1.4.
      Educational level was 7.4 years. The PANSS mean total score was 74.3. The mean
      daily dose, in chlorpromazine equivalents, was 523.9 mg/day. Four patients
      received a strict monotherapy of antipsychotics, while the other patients were
      receiving an association of two neuroleptics. The prevalence of NSS was 100% (cut
      off point=11) with a mean total score of 29.3+/-4.1. The highest score was for
      the motor coordination (10.1). As for the control group, the mean total score was
      7+/-1.3. A highly significant difference was found between patients and controls
      for all sub-scores of NSS. Negative correlations were found in patients, between
      age and neurological soft signs total score (P=0.05; r=-0.57) and also with
      sensory integration score (P=0.04; r=-0.58). The NSS total score was also
      correlated with low educational level (P=0.03; r=-0.61). There was no correlation
      between neurological soft signs scores and PANSS scores or the daily dose of
      antipsychotics. CONCLUSION: The prevalence and NSS scores are high among young
      people with early onset schizophrenia diagnosis illustrating the existence of
      structural abnormalities of the brain, themselves consequences of early
      neurodevelopmental disturbances, which would support the neurodevelopmental
      hypothesis concerning this pathology.

PMID- 24854725
TI  - ED plaster-of-Paris jacket for infantile scoliosis.
AB  - BACKGROUND: There are various articles published in last few years which consider
      surgical methods like growing rod instrumentation and modulation of the growth as
      a "gold standard" for the treatment of early onset severe scoliosis. We emphasize
      orthopaedic correction with serial casting as another option for such progressive
      deformity. The key to the success of this treatment is to understand the strategy
      and the technique involved in the effective casting. METHODS: The conventional
      technique of elongation, derotation, flexion cast (named EDF by Cotrel) is
      described with some modifications like wedging the cast (gypsotomy) in order to
      produce the flexion component. RESULTS: Serial casting with ED casts for the
      treatment of progressive idiopathic infantile scoliosis is an effective tool for
      the benign types of curves (Mehta) and spinal fusion was not necessary in two
      third of our cases. CONCLUSION: Surgical option for treatment of early onset
      scoliosis is not a "gold standard". Orthopaedic treatment with serial elongation,
      derotation casts remain the centerpiece of this treatment. Each detail to
      understand the technique must be known in order to obtain the best result.

PMID- 24854728
TI  - Journal of business continuity and emergency planning.

PMID- 24854726
TI  - Restoration of thoracic kyphosis by simultaneous translation on two rods for
      adolescent idiopathic scoliosis.
AB  - INTRODUCTION: Sagittal and axial corrections of the three-dimensional deformity
      characteristic of scoliosis remain challenging. MATERIALS AND METHOD: The author
      developed a new technique for scoliosis correction consisting of the translation
      of vertebrae simultaneously towards two rods, which are pre-bent to the correct
      sagittal profile. Using two rods ensures both reduction and stabilization of the
      curve. The system includes stable anchorages with polyaxial-threaded extensions
      that connect to the rods. Deformity reduction is done by tightening nuts
      simultaneously and progressively on the two rods. Results demonstrate the
      efficiency of this technique to achieve normal thoracic kyphosis (>20 degrees )
      in all 99 patients, with a mean gain of 19 degrees  of thoracic kyphosis in
      hypokyphotic cases. Coronal correction was 70-80% with a vertebral rotation gain
      of 40% where derotation connectors were used. CONCLUSIONS: In a large consecutive
      series of patients, this new technique allows to achieve a good 3D correction of
      the scoliosis.

PMID- 24854727
TI  - Comment on Guo et al. entitled "a prospective randomized controlled study on the
      treatment outcome of SpineCor brace versus rigid brace for adolescent idiopathic
      scoliosis with follow-up according to the SRS standardized criteria".

PMID- 24854729
TI  - Ensuring IT service continuity in the face of increasing threats.
AB  - How is IT service continuity related to business continuity management? Is it
      just a glorified disaster recovery procedure? Will IT service continuity help
      increase the assurance of IT services from the business owner to the customer?
      This paper is an attempt at answering these and many such questions. It is
      presented as a case study of IT service continuity management implementation at
      Emirates Group IT, Dubai. It takes the reader through the need for the process as
      felt by the business, through the learning acquired during implementation, to the
      practices deployed for managing the process on an ongoing basis. It provides a
      detailed view of the kind of pitfalls that could be encountered during
      implementation of the IT service continuity management process in a large-scale
      enterprise. 

PMID- 24854730
TI  - Building a global business continuity programme.
AB  - Business continuity programmes provide an important function within
      organisations, especially when aligned with and supportive of the organisation's
      goals, objectives and organisational culture. Continuity programmes for large,
      complex international organisations, unlike those for compact national companies,
      are more difficult to design, build, implement and maintain. Programmes for
      international organisations require attention to structural design, support
      across organisational leadership and hierarchy, seamless integration with the
      organisation's culture, measured success and demonstrated value. This paper
      details practical, but sometimes overlooked considerations for building
      successful global business continuity programmes. 

PMID- 24854731
TI  - Operation crash and surge: lessons learned from a region-wide exercise.
AB  - The Homeland Security Exercise and Evaluation Program (HSEEP) provides base
      guidance for planning all levels of public safety exercises, from simple seminars
      to complex full-scale exercises. However, the recent emphasis placed on the
      Federal Emergency Response Agency Whole Community approach to emergency
      management involves broadening the spectrum of participants to include multiple
      community partners. The magnitude and complexity of these exercises necessitates
      the incorporation of additional planning strategies beyond HSEEP guidance. The
      objective of this paper is to offer insight on effectively planning, running and
      learning from a region-wide multi-agency, multi-discipline, full-scale exercise.
      This will be achieved by utilising a case study to outline the planning process
      and lessons learned from managing the interaction of components, with an emphasis
      on achieving common goals without compromising individual needs. Additionally,
      this article complements 'Plane down in the city: Operation Crash and Surge',
      written by Duane F. Kann and Thomas W. Draper, and published in Volume 7 Number 3
      of this journal. 

PMID- 24854732
TI  - Collaboration in crisis and emergency management: Identifying the gaps in the
      case of storm 'Alexa'.
AB  - Failing to collaborate in crisis and emergency situations will increase the
      vulnerability of organisations and societies towards potential disasters. This
      paper highlights the significance of effective collaboration at different levels
      in times of crises. The case of snow storm 'Alexa', which hit Jordan in December
      2013, was considered for the purpose of this research. The impact of Alexa raised
      many questions regarding the country's preparedness and the capacity of its
      infrastructure to maintain critical business functions across various industry
      sectors. First, should people individually take all the responsibility to manage
      crises and emergencies in order to protect themselves and their belongings?
      Secondly, should organisations join efforts with other organisations within the
      same or different sectors? Thirdly, should governments seek external
      collaboration for the ultimate goal of securing their economies? These issues are
      significant as they underline the element of collaboration. This paper
      contributes to the understanding of the role of collaboration in times of intense
      difficulty and loss of control. The proposition made by this research is that an
      effective collaborative process is positively associated with perceptions of
      improved disaster risk reduction practices. 

PMID- 24854733
TI  - Understanding where policies and decisions can go wrong: utilising a 360 analysis
      model as a proactive reputation management strategy.
AB  - An organisation's reputation is its most relevant asset. The perceptions of the
      various audiences with which an organisation interacts both directly and
      indirectly can enhance or destroy that reputation. Due to the critical role these
      audiences play in an organisation's reputation, they should be actively
      considered as a part of an organisation's reputation management strategy. This
      paper introduces the 360 analysis model, which considers the benefits, detriments
      and potential fallout in regard to different audiences when creating policy or
      making important organisational decisions. The model's goal is to foster well
      considered policy and decisions that proactively protect an organisation's
      reputation. The model is also designed to be used as a research construct that
      can be utilised in the expansion of the reputation management literature in
      regard to heterogeneity and dynamics within and across audiences that can have an
      impact on an organisation's reputation. 

PMID- 24854734
TI  - Lessons learned from the Philippine government's response to Typhoon Haiyan.
AB  - Typhoon Haiyan was the strongest tropical cyclone to have ever hit land and
      provides an opportunity to analyse the application of emergency management
      principles in disaster response. In this case study, the author seeks to
      objectively assess the Philippine government's response before, during and after
      Typhoon Haiyan according to these principles. The study refers to the Philippine
      legislative and institutional framework as well as the government's overall
      response in relation to these principles. This study hopes to provide a resource
      for emergency management professionals, especially in the public administration
      and defence sector, in dealing with similar disasters and adopting potentially
      life-saving interventions. 

PMID- 24854735
TI  - A dynamic process of health risk assessment for business continuity management
      during the World Exposition Shanghai, China, 2010.
AB  - Reports of health issues related to mass gatherings around the world have
      indicated a potential for public health and medical emergencies to occur on a
      scale that could place a significant impact on business continuity for national
      and international organisations. This paper describes a risk assessment process
      for business continuity management that was performed as part of the planning
      efforts related to the World Expo 2010 Shanghai China (Expo), the world's largest
      mass gathering to date. Altogether, 73 million visitors attended the Expo,
      generating over US$2bn of revenue. During 2008 to 2010, the Shanghai Municipal
      Center for Disease Control and Prevention performed a dynamic series of four
      disaster risk assessments before and during the Expo. The purpose of this
      assessment process was to identify, analyse and evaluate risks for public health
      security during different stages of the Expo. This paper describes an overview of
      the novel approach for this multiple and dynamic process of assessment of health
      security risk for ensuring business continuity. 

PMID- 24854736
TI  - The Glu216/Ser218 pocket is a major determinant of spermine oxidase substrate
      specificity.
AB  - SMO (spermine oxidase) and APAO (acetylpolyamine oxidase) are flavoenzymes that
      play a critical role in the catabolism of polyamines. Polyamines are basic
      regulators of cell growth and proliferation and their homoeostasis is crucial for
      cell life since dysregulation of polyamine metabolism has been linked with
      cancer. In vertebrates SMO specifically catalyses the oxidation of spermine,
      whereas APAO displays a wider specificity, being able to oxidize both N1
      acetylspermine and N1-acetylspermidine, but not spermine. The molecular bases of
      the different substrate specificity of these two enzymes have remained so far
      elusive. However, previous molecular modelling, site-directed mutagenesis and
      biochemical characterization studies of the SMO enzyme-substrate complex have
      identified Glu216-Ser218 as a putative active site hot spot responsible for SMO
      substrate specificity. On the basis of these analyses, the SMO double mutants
      E216L/S218A and E216T/S218A have been produced and characterized by CD
      spectroscopy and steady-state and rapid kinetics experiments. The results
      obtained demonstrate that mutation E216L/S218A endows SMO with N1-acetylspermine
      oxidase activity, uncovering one of the structural determinants that confer the
      exquisite and exclusive substrate specificity of SMO for spermine. These results
      provide the theoretical bases for the design of specific inhibitors either for
      SMO or APAO.

PMID- 24854738
TI  - Requirement of simultaneous assessment of crystal- and supernatant-related
      entomotoxic activities of Bacillus thuringiensis strains for biocontrol-product
      development.
AB  - Bioinsecticides with lower concentrations of endospores/crystals and without loss
      of efficiency are economically advantageous for pest biocontrol. In addition to
      Cry proteins, other Bacillus thuringiensis (Bt) toxins in culture supernatants
      (SN) have biocontrol potential (e.g., Vip3A, Cry1I, Sip1), whereas others are
      unwanted (beta-exotoxins), as they display widespread toxicity across taxa. A
      strain simultaneously providing distinct toxin activities in crystals and SN
      would be desirable for bioinsecticides development; however, strains secreting
      beta-exotoxins should be discarded, independently of other useful entomotoxins.
      Entomotoxicity of crystals and SN from a Brazilian Bt tolworthi strain (Btt01)
      was tested against Spodoptera frugiperda to assess the potential for biocontrol
      product development based on more than one type of toxin/activity. Tests showed
      that 10(7) endospores mL(-1) caused >80% of larvae mortality, suggesting Btt01
      may be used in similar concentrations as those of other Bt-based biopesticides.
      When it was applied to cornfields, a significant 60% reduction of larvae
      infestation was observed. However, bioassays with Btt01 SN revealed a
      thermostable toxic activity. Physicochemical characterization strongly suggests
      the presence of unwanted beta-exotoxins, with isolate-specific temporal variation
      in its secretion. Knowledge of the temporal pattern of secretion/activity in
      culture for all forms of toxins produced by a single strain is required to both
      detect useful activities and avoid the potential lack of identification of
      undesirable toxins. These findings are discussed in the contexts of commercial Bt
      product development, advantages of multiple-activity strains, and care and
      handling recommended for large-scale fermentation systems.

PMID- 24854743
TI  - [Exploring new assessment methods to evaluate motor and non-motor symptoms
      comprehensively and objectively in patients with Parkinson's disease].

PMID- 24854739
TI  - Extract-filter-shoot liquid chromatography with mass spectrometry for the
      analysis of vitamin D2 in a powdered supplement capsule and standard reference
      material 3280.
AB  - An "extract-filter-shoot" method for the analysis of vitamin D2, ergocalciferol,
      in a dry powdered dietary supplement capsule containing rice flour excipient and
      in a National Institute of Standards and Technology standard reference material
      3280 is reported. Quantification of vitamin D2 was done by atmospheric pressure
      chemical ionization mass spectrometry using selected ion monitoring, two
      transitions of selected reaction monitoring, and extracted ion chromatograms from
      full scans. UV detection was used for the quantification of Vitamin D2 in the dry
      powder capsule, whereas interfering species rendered UV detection unreliable for
      standard reference material 3280. Average values for standard reference material
      3280 ranged from 8.27 +/- 0.58 to 8.33 +/- 0.57 MUg/g using internal standard
      calibration and response factor approaches, compared to the previous National
      Institute of Standards and Technology internal value for vitamin D2 of 8.78 +/-
      0.11 MUg/g, and the recently updated reference value of 8.6 +/- 2.6 MUg/g. The
      powdered supplement capsule was found to contain 28.19 +/- 0.35 to 28.67 +/- 0.90
      MUg/capsule for a capsule labeled to contain 25.00 MUg. The triacylglycerol
      composition of the rice flour excipient in the powdered supplement capsule
      determined by atmospheric pressure chemical ionization mass spectrometry is also
      reported.

PMID- 24854737
TI  - Structural and functional brain alterations in end stage renal disease patients
      on routine hemodialysis: a voxel-based morphometry and resting state functional
      connectivity study.
AB  - BACKGROUND AND PURPOSE: Cognitive impairment is a well-described phenomenon in
      end-stage renal disease (ESRD) patients. However, its pathogenesis remains poorly
      understood. The primary focus of this study was to examine structural and
      functional brain deficits in ESRD patients. MATERIALS AND METHODS: Thirty ESRD
      patients on hemodialysis (without clinical neurological disease) and 30 age- and
      gender-matched control individuals (without renal or neurological problems) were
      recruited in a prospective, single-center study. High-resolution structural
      magnetic resonance imaging (MRI) and resting state functional MRI were performed
      on both groups to detect the subtle cerebral deficits in ESRD patients. Voxel
      based morphometry was used to characterize gray matter deficits in ESRD patients.
      The impact of abnormal morphometry on the cerebral functional integrity was
      investigated by evaluating the alterations in resting state functional
      connectivity when brain regions with gray matter volume reduction were used as
      seed areas. RESULTS: A significant decrease in gray matter volume was observed in
      ESRD patients in the bilateral medial orbito-prefrontal cortices, bilateral
      dorsal lateral prefrontal cortices, and the left middle temporal cortex. When
      brain regions with gray matter volume reduction were used as seed areas, the
      integration was found to be significantly decreased in ESRD patients in the
      fronto-cerebellum circuits and within prefrontal circuits. In addition,
      significantly enhanced functional connectivity was found between the prefrontal
      cortex and the left temporal cortex and within the prefrontal circuits.
      CONCLUSIONS: Our study revealed that both the structural and functional cerebral
      cortices were impaired in ESRD patients on routine hemodialysis.

PMID- 24854744
TI  - [Preliminary relationship between serum cystatin C level and Parkinson's
      disease].
AB  - OBJECTIVE: To explore the role of serum cystatin C level in Parkinson's disease
      (PD) and evaluate the relationship between cystatin C level and clinical
      characteristics and different stages of PD. METHODS: A total of 115 PD patients
      and 110 healthy controls were recruited. The results of such routine laboratory
      tests as triglyceride, cholesterol, low-density lipoprotein (LDL), high-density
      lipoprotein (HDL), creatinine, urea, uric acid and cystatin C were assessed from
      fasting blood samples at our clinical laboratory center. They were further
      divided into subgroups according to Hoehn & Yahr (H&Y) staging. Statistical
      analysis was performed with SPSS version 17.0 software. RESULTS: Compared to
      controls (0.96 +/- 0.16 mg/L), the mean serum level of cystatin C was
      significantly higher in PD patients (1.06 +/- 0.20 mg/L). Spearman's correlation
      analyses showed a positive and significant correlation between cystatin C levels
      and age as well as creatinine levels. Correlation was not found between cystatin
      C level and triglyceride, cholesterol, LDL, HDL, urea or uric acid. ANOVA
      analysis showed that cystatin C had a higher level during the middle and late
      stages of PD than that during the early stage. CONCLUSION: Cystatin C level may
      play an important role in the progression of PD.

PMID- 24854745
TI  - [Association between polymorphism of dopamine beta-hydroxylase gene and
      Parkinson's disease in Uygurs and Hans of Xinjiang].
AB  - OBJECTIVE: To explore the relationship between dopamine beta-hydroxylase gene
      polymorphisms and Parkinson's disease (PD) in Uygurs and Hans populations of
      Xinjiang. METHODS: The polymorphisms of DBH gene were determined by polymerase
      chain-reaction restriction fragment length polymorphism (PCR-RFLP) in 239 PD
      patients (including 100 Uygurs and 141 Hans) and 232 health controls (including
      103 Uygurs and 129 Hans). RESULTS: The genotypic or allelic distribution of DBH
      gene had significant differences between PD and control groups in both Uygur and
      Han populations (P < 0.05). The genotypic or allelic frequencies were
      significantly different between Han PD and control groups (P < 0.05). The
      genotypic or allelic frequencies in those aged 65 years or above were
      significantly different from that in others (P < 0.05). There was a significant
      increase of PD in A2 allele carriers (OR = 1.965, P < 0.05). And the frequencies
      of A2 allele in female PD patients were higher than those in female controls (P <
      0.05) and A2 allele carriers had a significant increase of PD (OR = 1.696, P <
      0.05). CONCLUSION: Different between Uygurs and Hans of Xinjiang, DBH5 TaqI
      polymorphisms may be associated with PD in Hans. A2 allele carriers are often
      found in females and those aged 65 years or above.

PMID- 24854746
TI  - [Effects of non-motor symptoms on health-related quality of life in Parkinson's
      disease].
AB  - OBJECTIVE: To explore the effects of non-motor symptoms (NMS) on health-related
      quality of life (HRQOL) in Parkinson's disease (PD) patients. METHODS: By
      convenient sampling, 128 PD patients were recruited. NMS was assessed by the non
      motor symptoms scale for PD (NMSS) and HRQOL by the 39-item PD Questionnaire
      (PDQ39). RESULTS: All PD patients (100%) had NMS with a general score of (124 +/-
      48) . Among these NMS, constipation was ranked the highest and the general level
      of NMS was significantly positively associated with age (r = 0.226, P < 0.05),
      Hoehn-Yahr staging (r = 0.442, P < 0.05) and disease course (r = 0.223, P <
      0.05). However there was no correlation with gender (r = 0.085, P < 0.05). For PD
      patients, HRQOL became impaired with a general score of (44 +/- 16) . Activities
      of daily living (60 +/- 15), mobility (49 +/- 21), emotional well-being (49 +/-
      28) and stigma (48 +/- 46) were the most seriously affected. Females (chi2 = 
      1.821 P < 0.05) and senile bereaved patients (chi2 = -1.512, P < 0.05) had
      significantly lower HRQOL than that of others. For PD patients, the general level
      of HRQOL was significantly positively associated with disease course (r = 0.260,
      P < 0.05) and severity (r = 0.259, P < 0.05). The general level of HRQOL was
      significantly positively associated with the general level of NMS (r = 0.686, P <
      0.01). CONCLUSION: Non-motor symptoms (NMS) are quite common in PD patients. For
      PD patients, NMS has a more negative impact on HRQOL than other symptoms.

PMID- 24854747
TI  - [Changes of left ventricular systolic and diastolic function and the diagnostic
      value of B-type natriuretic peptide in patients with sepsis].
AB  - OBJECTIVE: To explore the diagnostic value of transthoracic echocardiogram (TTE)
      and/or plasma B-type natriuretic peptide (BNP) for left ventricular (LV) systolic
      dysfunction and/or LV diastolic dysfunction in septic patients. METHODS: In this
      prospective observational study, 90 septic patients and 30 non-septic ones
      underwent serial TTEs to measure LV ejection fraction (LVEF) and blood flow
      velocity of mitral annulus during early diastole (E) and atrial contraction (A)
      ratio (E/A) within 24 h of admission, 2, 3, 5 and 7 days. Enzyme-linked
      immunosorbent assay (ELISA) was used to detect the plasma levels of BNP
      simultaneously. Patient medical records were used to obtain the information of
      demographics, APACHE II scores and 28-day survival rates. RESULTS: LVEF and E/A
      decreased significantly more in sepsis group (P = 0.00) while BNP elevated in
      sepsis group (P = 0.00). LVEF and E/A showed an initial drop and a subsequent
      rise. On the contrary, BNP increased and then decreased. There was a positive
      correlation between LVEF and E/A (r = 0.670, P = 0.00) while BNP level had a
      negative correlation with LVEF and E/A (r1 = -0.733, P1 = 0.00; r2 = -0.929, P2 =
      0.00). Receiver operating characteristic (ROC) curve analysis showed that a
      cutoff point of BNP at 536.3 ng/L for diagnosing sepsis-induced LV systolic
      dysfunction had a sensitivity of 84.4% and a specificity of 68.7%. When at 505.0
      ng/L, the valves were 56.0% and 97.4% respectively. CONCLUSION: TTE may uncover
      septic patients whose LV diastolic dysfunction occurs earlier and reverses later
      than systolic type. And it may also participate in systolic dysfunction. The
      levels of BNP, probably as an adjustment to LV function, are more closely aligned
      with the severity of septic LV diastolic dysfunction. The combined application of
      TTE and plasma BNP appears to be efficacious for dynamically assessing cardiac
      function in septic patients.

PMID- 24854748
TI  - [Systematic review of primary stenting for arteriosclerotic occlusion in below
      the-knee arteries].
AB  - OBJECTIVE: To evaluate the clinical value of primary stenting for treating
      peripheral arterial diseases in below-the-knee arteries by comparing to
      percutaneous transluminal angioplasty (PTA). METHODS: PubMed, ScienceDirect,
      Embase, and CBM databases were searched for relevant articles. Based on the
      different types of stents, we divided the primary stent group into the bare metal
      stent(BMS) group and drug-eluting stent(DES) group. The outcome measures were
      immediate technical success, freedom from target vessel revascularization (TVR
      free) rate and limb salvage. RESULTS: Finally, 14 studies (published between 2001
      and 2012) satisfying the inclusion criteria were identified. A total of 3 278
      patients and 3 699 limbs constituted our final study population. The technical
      success rate of PTA was 90.95% (95% confidence interval (CI) 86.25%-94.15%). Only
      one study reported a technical failure of 4% (5/118) in the primary stent group.
      There were no significant differences in the 1-year primary patency and TVR-free
      rates between the PTA group and BMS groups (P > 0.05 and P > 0.05), respectively.
      The pooled estimates of 1-year primary patency and TVR-free rate in DES group
      were 85.05% (95%CI 79.95%-89.02%) and 90.52% (95%CI 83.68%-94.67%), respectively,
      which were better than those of the BMS (P < 0.001) and PTA groups (P < 0.001).
      The pooled estimate of 1-year limb salvage in the PTA, BMS, and DES groups was
      88.41% (95%CI 84.53%-91.43%), 94.41% (95%CI 89.52%-97.1%), and 96.81% (95%CI
      94.04%-98.32%), respectively. The BMS and DES groups had higher limb salvage
      rates than the PTA group (P < 0.001 for both comparisons). The rates of severe
      complications were low both in the PTA and primary stent groups. Although the
      influence analysis showed rather robust results, the heterogeneity was quite high
      and they were not adjusted for confounding variables. CONCLUSION: Primary BMS
      implantation had no advantage over PTA in reducing restenosis or
      revascularization for infrapopliteal disease. Primary DES implantation seems to
      be a promising treatment for focal infrapopliteal lesions.

PMID- 24854749
TI  - [Diagnostic and therapeutic analysis of malignant carotid body tumors].
AB  - OBJECTIVE: To analyze the diagnosis, treatment and prognosis of the malignant
      carotid body tumor. METHODS: The data of pathology, diagnosis, therapy and follow
      up of seven patients with malignant carotid body tumor in Peking Union Medical
      College Hospital from Dec 1949 to Dec 2012 were analyzed retrospectively.
      RESULTS: 2 cases without the tumor resection. 5 cases were treated with surgical
      methods, 4 cases with tumor resection and external carotid artery ligation, 1
      case with tumor resection and reconstruction of internal carotid artery with
      saphenous vein. Cranial nerve palsy occurred in 5 cases, of which 3 occurred
      hypoglossal nerve damage, 2 cases occurred vagus damage, 1 case with hypoglossal,
      vagus and sympathetic nerve damage. Follow-up was from 2 to 12 years. local tumor
      recurrence happened in 2-year postoperation and got remote bone and pancreas
      metastasis in 5-year postoperation in one case, and finally died in 7-year
      postoperation. 1 case had the internal carotid artery restenosis severely in 1
      year postoperation, then performed the stent treatment. 2 cases without operation
      were still alive. Interestingly, the tumor after radiotherapy was steady in one
      case. The other received the tumor resection because of the severe syndrome after
      8 years. CONCLUSION: the diagnosis of malignant carotid body tumor should base on
      occurring extensive invasion of adjacent organs, metastasis and pathology. Early
      stage surgical excision can reduce the recurrence and complication. Radiotherapy
      can effectively control local size and distant metastasis.

PMID- 24854750
TI  - [Imaging assessing symptomatic vertebral compression fracture to be treated by
      vertebroplasty and kyphoplasty in osteoporosis patients].
AB  - OBJECTIVE: To evaluate the values of radiology, computed tomography (CT) and
      magnetic resonance imaging (MRI) in assessing symptomatic osteoporosis vertebral
      compression fractures in vertebroplasty and kyphoplasty. METHODS: Retrospective
      reviews were conducted for 41 osteoporotic vertebral compression fractures
      patients with preoperative CT (with 3D reconstruction)/MRI (with fat saturation
      sequence) and preoperative and postoperative radiological imaging data. All
      patients underwent percutaneous vertebroplasty (PVP) or balloon kyphoplasty (BKP)
      when conservative treatment failed to offer pain relief. RESULTS: CT scan showed
      52 vertebral fractures while MRI detected a total of 70 lesions of vertebral
      body, including 44 new fractures, 8 old fractures and 18 bone bruises. Eight old
      fractures and 2 mild bone bruises were treated conservatively. In conjunctions
      with MRI, especially fat saturation sequence, 60 therapeutic vertebral bodies
      were visualized. It was superior to CT. As demonstrated by preoperative and
      postoperative radiology, vertebral body height improved and Cobb Angle slightly
      decreased for 60 lesions. CONCLUSION: For vertebral compression fractures in
      osteoporosis patients, preoperative CT and MRI examinations have important
      clinical significance in providing treatment guidance and assessing postoperative
      outcomes.

PMID- 24854751
TI  - [Proximal femoral nail antirotation versus dynamic hip screw for
      intertrochanteric fracture in elders: a meta-analysis].
AB  - OBJECTIVE: To assess the efficacies of proximal femoral nail antirotation (PFNA)
      versus dynamic hip screw (DHS) for intertrochanteric fracture in elders. METHODS:
      The databases of PubMed, Embase, CENTRAL, CBM, CNKI and WANFANG were searched for
      the relevant randomized controlled trials (RCTs) up to May 18, 2013. After
      quality evaluation and data extraction by two authors independently, meta
      analyses were performed with the RevMan5.1 software. And the levels of evidence
      were evaluated by the GRADEprofile 3.6 software. RESULTS: A total of 17 studies
      (n = 1 344) were included and there were 656 patients in PFNA group and 688 in
      DHS respectively. Meta-analyses showed that, as compared with DHS, PFNA could
      significantly decrease fixation failure rate (odds ratio (OR) = 0.26, 95%
      confidence interval (CI) = [0.12, 0.57], P = 0.0008), reduce average fracture
      healing time (weighted mean difference (WMD) = -15.11, 95%CI = [-24.36, -5.85], P
      = 0.001), improve excellent and good rate for Harris score (OR = 0.29, 95%CI =
      [0.15, 0.56], P = 0.0002), yield a higher Harris score (WMD = 6.88, 95%CI =
      [0.96, 12.80], P = 0.02) and reduce the rate of coxa vara (OR = 0.40, 95%CI =
      [0.18,0.92], P = 0.03). However, there was no statistical significance in 1-year
      mortality, postoperative nonunion and delayed union, postoperative femoral head
      necrosis, postoperative femoral fractures or femoral head necrosis. The
      importance of outcomes was "critical". And the level of evidences based on the
      GRADE approach was from "very low" to "low". CONCLUSION: PFNA is superior to DHS.
      Due to the limitations of the included studies, more large-sample and high
      quality RCTs are required. And subgroup analysis based on fracture types should
      be performed.

PMID- 24854752
TI  - [Surgical application of pedicle drill template navigation technology for
      complicated scoliosis].
AB  - OBJECTIVE: To evaluate the surgical efficacy and significance of pedicle drill
      template navigation technology for severe complicated scoliosis. METHODS:
      Retrospective analyses were performed for 8 patients with complicated spinal
      scoliosis during 2010-2013. There were 5 males and 3 females with an average age
      of 18 (9-23) years. There were congenital (n = 5) and idiopathic (n = 3)
      scoliosis. A three-dimensional spinal computed tomography (CT) scan was
      performed. And the data were acquired and transferred via a DICOM network to a
      computer workstation. Three-dimensional reconstruction and rapid prototype were
      obtained. The navigation drill template was manufactured by rapid prototyping for
      clinical operation. Eight matched patients without navigation drill template were
      selected into a control group. RESULTS: Eight patients were successfully operated
      as planned without any complication of spinal cord, nerve or blood vessel injury.
      And their post-operative outcomes were satisfactory. The intra-operative findings
      were the same as pre-operative impressions and measurements by digital spinal
      three dimensional reconstructions. The results of pedicle drill template
      navigation were excellent and the position of pedicle screws was accurate as
      evaluated by postoperative radiology and CT scan. The correction rate of
      scoliosis was 60%. Navigation drill template group: the average operating
      duration was 186 min, average volume of blood loss 460 ml and frequency of
      radiation by C arm 4 times. CONTROL GROUP: the average operating duration was 225
      min, average volume of blood loss 550 ml and frequency of radiation by C arm 30
      times. The average operative duration between two groups was statistically
      significant (P < 0.01, t-test). And so were average volume of blood loss and
      frequency of radiation. CONCLUSION: The rapid prototyping of pedicle drill
      template navigation technology is a new method for accurate intra-operative
      insertion of pedicle screws. It has a high surgical accuracy and safety for
      spinal scoliosis. The application of pedicle drill template navigation is simple
      without special experience requirements for operators. It can shorten the
      operative duration and reduce blood lose. The exposure of operators to radiation
      may be reduced or avoided during fluoroscopy.

PMID- 24854753
TI  - [Study on 21 cases of multiple primary lung cancer].
AB  - OBJECTIVE: To explore the clinical characteristics of multiple primary lung
      cancer (MPLC) and provide potential clues to the early diagnosis and treatment
      selection of MPLC patients. METHODS: The clinical data of 21 patients with MPLC
      confirmed by postoperative histopathology were analyzed retrospectively. RESULTS:
      All the 21 patients received surgery (pulmonary lobectomy or pulmonary wedge
      resection), and 49 intrapulmonary tumors were resected. The histopathological
      examination demonstrated that all the 21 cases were MPLC. Among the 21 patients,
      10 had bilateral lesions in lung and 11 had unilateral lesions; 17 suffered
      synchronous and 4 suffered metachronous tumors; 14 had double two primary tumors,
      6 had three primary tumors and 1 had four primary tumors. In these patients, 2
      had various histological subtypes among their multiple lesions and 19 had same
      histological subtypes among their multiple tumors; 14 cases with stage I disease,
      stage II 2 cases, stage III 5 cases. CONCLUSIONS: For the patients who were
      detected as MPLC by diagnostic imaging examination, more positive therapeutic
      decision, such as surgery, could be suggested. The molecular markers should be
      developed for assisting diagnosis of MPLC.

PMID- 24854754
TI  - [Analysis of reoperation for infertility women with tubal pregnancy after
      conservative surgery].
AB  - OBJECTIVE: To evaluate the cause of infertility and tubal abnormality in women of
      tubal pregnancy after conservative treatment with laparotomy or laparoscopy
      through a combination of laparoscopy, hysteroscopic tubal catheterization and
      hydrotubation. METHODS: Laparoscopy was performed to observe pelvic adhesions,
      tube shape, fimbriated extremity of fallopian and other factors related with
      infertility for 37 inpatients with infertility after tubal pregnancy and
      undergoing conservative surgery during December 2008 and October 2010. Meanwhile,
      hysteroscopic tubal catheterization and hydrotubation were performed with
      laparoscopy to examine tube patency. RESULTS: Among them, 97.3% had tube
      infertility caused by tube abnormality and adhesions, or tube obstruction alone
      or concurrently. For all tubes, tube obstruction accounted for 79.7% (59/74) ,
      fimbrial occlusion of fallopian tube 54.1% (40/74) and tube abnormality 52.7%
      (39/74) . Pelvic adhesion occurred at a rate of 89.2% and there were I degree
      (21.6%), II degree (32.4%), III degree (35.1%) and IV degree (0). For tubes with
      pregnancy history, 48.6% showed tube abnormality, 45.9% fimbrial occlusion of
      fallopian tube and 75.7% (28/37) tube obstruction. Comparatively, for the tubes
      without pregnancy history, 56.8%showed tube abnormality, 62.2%fimbrial occlusion
      of fallopian tube and 86.5%tube obstruction. No significant difference existed in
      tube shape, umbrella end and tube obstruction between the tubes with pregnancy
      history and those without pregnancy history. Neither statistically significant
      difference was found in adhesion degree, tube shape, umbrella end and tube
      obstruction of diseased and normal tubes between laparotomy and laparoscopy
      groups. CONCLUSION: Infertility of women after tubal pregnancy and conservative
      surgery is mainly caused by abnormal tube including pelvic adhesion, tube
      morphological abnormality and tube obstruction. No marked inter-group difference
      exists in fertility damage after conservative surgery with laparotomy or
      laparoscopy.

PMID- 24854755
TI  - [Clinical study of gasless abdominal-wall lifting laparoscopic myomectomy with 5
      mm laparoscope].
AB  - OBJECTIVE: To explore the feasibility, advantages and clinical value of gasless
      abdominal-wall lifting laparoscopic myomectomy with 5 mm laparoscope and 2
      abdominal holes (1.5-hole-gasless-laparoscopic myomectomy). METHODS: A total of
      90 cases of uterine fibroids were randomly divided into 2 groups. Lifting gasless
      group (n = 46) underwent gasless abdominal-wall lifting laparoscopic myomectomy
      with 5 mm laparoscope and 2 abdominal holes, and pneumoperitoneum group (n = 44)
      pneumoperitoneum laparoscopic myomectomy. The operative duration, blood loss
      volume, average time of single-myoma-removal, intestinal function recovery and
      hospital stay of both groups were compared. RESULTS: The operative duration,
      blood loss volume and average time of single-myoma-removal of lifting gasless
      group were respectively significantly less than those of pneumoperitoneum group
      (P < 0.01) . The postoperative intestinal function recovery and postoperative
      hospital stay had no significant difference between two groups (P > 0.05). Three
      cases of pneumoperitoneum group were converted successfully into myomectomy with
      traditional 3-hole gasless abdominal wall lifting laparoscopy because of large
      fibroids in uterine isthmus. A total of 12 newly discovered myomas, not pre
      detected ultrasonically, were removed in 10 cases of lifting gasless group.
      CONCLUSION: 1.5-hole-gasless-laparoscopic myomectomy, like traditional gasless
      laparoscopy, may avoid the complications of laparoscopic CO2 pneumoperitoneum.
      The smaller laparoscope-hole and sole operating hole make this maneuver a safe,
      easy and mini-invasive procedure. It is more suitable for clinical application
      and popularity in primary care.

PMID- 24854756
TI  - [Clinico-electrophysiological and pathological characteristics of neuropathy in
      Sjogren's syndrome: a report of 5 cases].
AB  - OBJECTIVE: To summarize the clinical features, electrophysiological and
      neuropathological characteristics of peripheral nerves in patients with primary
      Sjogren's syndrome (SS). METHODS: We retrospectively analyzed the clinical,
      electrophysiological and neuropathological characteristics of 5 female SS
      patients with neuropathy complications undergoing electrophysiology and sural
      nerve biopsy at our department from January 2011 to June 2013. RESULTS: They had
      an age range of 20-75 years. The course of peripheral neuropathy ranged 0.5-60
      months and the whole course 12-240 months. pSS-associated neuropathy included
      multiple mononeuropathy (n = 1), symmetrical axonal sensorimotor polyneuropathy
      (n = 1) and sensory ganglioneuronopathy (n = 3). All biopsies showed varying
      degrees of myelinated fiber loss. Three biopsies had axonal degeneration
      associated with demyelination. However, there was no formation of onion bulb
      regeneration or plexus. Necrotizing vasculitis was diagnosed in 2 cases.
      CONCLUSION: The manifestations of peripheral nerve n pSS include multiple
      mononeuropathy, axonal symmetric sensorimotor polyneuropathy and sensory
      gangioneuronopathy. Sural biopsy shows typical necrotizing vasculitis in some
      cases and myelinated fiber loss and axonal degeneration in others. The pathogenic
      mechanisms of neurological involvement in pSS remain unknown. However,
      vasculitis, ischemic and immunological insults resulting in sensory
      gangioneuronopathy have been described.

PMID- 24854757
TI  - [Ultrasound-guided core needle biopsy on the thyroid nodules: the adequacy and
      the predicting factors for the nodule management].
AB  - OBJECTIVE: To explore the adequacy of the initial ultrasound-guided core needle
      biopsy (CNB) on the thyroid nodules and the potential factors for predicting the
      management of the nodules. METHODS: Retrospectively collected the subjects who
      underwent the CNB on the thyroid nodules within one year, with the inclusion
      criteria: (1) initial CNB on the thyroid nodules, (2) underwent the ultrasound
      scanning 1 month before the biopsy. The following data were recorded, which were
      the patient's age, sex, the lesion's sonographic findings (size, number, content,
      margin, echo, calcification, and internal vascularity), and histopathology. The
      CNB pathological diagnostic criterion was set up referring to the Bethesda System
      for Reporting Thyroid Cytopathology (BSRTC). RESULTS: One hundred and fifty-seven
      patients with 162 nodules were enrolled, and the adequacy of the CNB was 97.5%
      (158/162, 95%CI 93.8%-99.3%). Referring to the BSRTC, of all the 153 nodules with
      determined management, 64 (64/153, 41.8%, 95%CI 34.0%-49.6%) were to be followed
      up only, and 89 (89/153, 58.2%, 95%CI 50.4%-66.0%) were to be undergone nodule
      excision. Three of the sonographic findings, including lesion margin,
      echogenicity, and internal vascularity, were significantly associated with the
      management of the nodules (P < 0.05), and the internal vascularity and margin
      were demonstrated as the independent factors for predicting the nodule excision
      by using the logistic regression model (Odds Ratio = 2.942, 2.767, P < 0.05).
      Only one case of moderate localized hematoma was observed in this series.
      CONCLUSION: As long as the specification of biopsy operation and pathology
      interpretation, the procedure of CNB on the thyroid nodules is safe with high
      adequacy as well. The sonographic margin and internal vascularity of the lesion
      are the independent factors for predicting the nodule excision.

PMID- 24854759
TI  - [Establishment of rabbit with acute cerebral infarction by intervention and
      evaluation of computed tomographic perfusion imaging].
AB  - OBJECTIVE: To discuss the establishment of acute cerebral infarction model in
      rabbits and evaluate the value of computed tomographic perfusion (CTP) imaging.
      METHODS: A total of 12 healthy adult New Zealand white rabbits were used. The
      model was established through femoral artery puncture and injecting autoblood
      clot into internal carotid artery through an inserted micro-catheter to occlude
      the artery. Digital subtraction angiography (DSA) cerebral angiography and CTP
      imaging were performed at 2 and 6 hours post-embolization. RESULTS: Super
      selective catheterization of internal carotid artery and an injection of auto
      blood clots were successfully accomplished in all rabbits and the success rate
      was 100%. DSA showed that middle cerebral artery and anterior cerebral artery
      narrowed. At 2 hours post-embolism, CTP showed cerebral blood flow (CBF) and
      cerebral blood volume (CBV) decreased and mean transit time (MTT) and time to
      peak (TTP) increased in cerebral ischemia area. Compared with the contralateral
      mirror area, CBF and CBV decreased in infarct area and MTT and TTP elongated with
      significant statistical difference at 2 and 6 hours (P < 0.01). CONCLUSION: The
      model of acute cerebral ischemia may be effectively established in rabbits. This
      micro-invasive technique is easily manipulated with a high success rate. And CTP
      is an effective way of diagnosing acute cerebral infarction.

PMID- 24854758
TI  - [Application of conscious sedation with dexmedetomidine and sufentanil in patient
      for plastic surgery].
AB  - OBJECTIVE: To observe the effectiveness of conscious sedation with
      dexmedetomidine and sufentanil in patients for plastic surgery. METHODS: Forty
      patients scheduled for elective plastic surgery under conscious sedation were
      infused 1 ug/kg intravenously within 15 minutes as loading dose followed by a
      continuous infusion of dexmedetomidine (0.5 ug.kg-1.h-1) and sufentanil (0.07
      ug.kg-1.h-1) respectively. Sufentanil 0.05 ug/kg and midazolam 0.025 mg/kg were
      administrated intravenously 5 minutes before local infiltration, and then a bolus
      of sufentanil or midazolam was given as needed to maintain OAA/S score of 11
      during the procedure. The drug infusion was discontinued at 5 to 10 min before
      the end of the surgical procedure. The complications (i.e. anoxemia, apnea,
      bradycardia, restlessness, nausea, vomiting, crying and excitation), if any,
      anesthesia duration and drug consumption were recorded. On the first
      postoperative day, patients were asked to rate their satisfaction with the
      anesthetic management and whether they would choose to receive the same sedative
      analgesic medications and should they require a similar surgical procedure in the
      future. RESULTS: The OAA/S score decreased from 20.0 +/- 0 to 11.5 +/- 2.5 after
      patients being infused the loading dose of dexmedetomidine, and was maintained
      10.5-11.1 during the procedure. At the end of the procedure, the OAA/S score
      return to 16.1 +/- 2.8. The induction of sedation produced a significant decrease
      in HR (P < 0.05) and no significant changes in SBP, DBP and RR values (P > 0.05).
      There were 38 patients completed their procedures under conscious sedation, and
      there were incident of crying and bradycardia in 5 and 2 patients respectively.
      The anesthesia duration and consumption of dexmedetomidine, sufentanil and
      midazolam were (128 +/- 47) min, (116 +/- 43) ug, (10 +/- 5) ug and (2 +/- 1) mg
      respectively. In an interview on the first postoperative day, there were 13
      patients complaining no memory, 17 patients complaining fuzzy memory and 8
      patients complaining awake during the procedure, respectively. There were 92% of
      the patients willing to receive the same anesthetic technique again in the
      future. CONCLUSION: Conscious sedation with dexmedetomidine and sufentanil is an
      effective anesthetic technique in patients for plastic surgery.

PMID- 24854760
TI  - [First domestic case of intracranial aneurysm parent artery remodeling hybrid
      surgery].
AB  - OBJECTIVE: To explore new treatment modalities for complex intracranial
      aneurysms. METHODS: Under general anesthesia, intracranial aneurysm parent artery
      remodeling surgery was performed along with repeated immediate intraoperative
      cerebral angiogram to verify the effect of revascularization and therefore adjust
      the operation plan accordingly. RESULTS: Aneurysm was successfully clipped
      without injuries of vascular branches. Prognosis was excellent. CONCLUSION:
      Complex hybrid surgery is an ideal option for parent artery remodeling of
      complicated intracranial aneurysms.

PMID- 24854761
TI  - Using interactive workshops to prompt knowledge exchange: a realist evaluation of
      a knowledge to action initiative.
AB  - INTRODUCTION: Interactive workshops are often the default mechanism for sharing
      knowledge across professional and sector boundaries; yet we understand little
      about if, and how, they work. Between 2009 and 2011, the Research to Reality
      programme in North East England ran eight stand-alone facilitated multi-agency
      workshops focused on priority public health issues. Local authorities, the health
      service, and academe collaborated on the programme to share latest evidence and
      best practice METHODS: A realist evaluation asked the overarching question 'what
      worked where, for whom, and under what conditions' regarding the knowledge
      exchange (KE) mechanisms underpinning any changes. Data were collected from fifty
      one interviews, six observations, and analysis of programme documentation.
      RESULTS: 191 delegates attended (local authority 46%, NHS 24%, academia 22%,
      third sector 6%, other 2%). The programme theory was that awareness raising and
      critical discussion would facilitate ownership and evidence uptake. KE activity
      included: research digests, academic and senior practitioner presentations, and
      facilitated round-table discussions. Joint action planning was used to prompt
      informed follow-up action. Participants valued the digests, expert input,
      opportunities for discussion, networking and 'space to think'. However, within a
      few months, sustainability was lost. There was no evidence of direct changes to
      practice. Multiple barriers to research utilization emerged. DISCUSSION: The
      findings suggest that in pressured contexts exacerbated by structural reform
      providing evidence summaries, input from academic and practice experts,
      conversational spaces and personal action planning are necessary to create
      enthusiasm on the day, but are insufficient to prompt practice change in the
      medium term. The findings question makes assumptions about the instrumental,
      linear use of knowledge and of change focused on individuals as a driver for
      organizational change. Delegates' views of 'what would work' are shared.
      Mechanisms that would enhance interactive formats are discussed.

PMID- 24854762
TI  - Beyond two communities - from research utilization and knowledge translation to
      co-production?
AB  - In recent public health discourse, the relations between researchers, policy
      makers, and professionals are often described as 'gaps', illustrating the
      (cultural) differences between these domains. Such descriptions seem to be part
      of a 'two communities'-logic: a perception that researchers and policy makers or
      professionals stem from strictly separated worlds, with distinctive logics,
      rationales and incentives. In this paper, the author will argue that this
      prevalent conceptual framework of 'two communities', whilst having been extremely
      helpful in theorizing the difficulties of connecting policy needs with research
      findings, bears several important limitations when analysing structural
      collaboratives between researchers and policy makers or professionals. The paper
      outlines several problematic assumptions and neglected elements that are
      generally perceivable within this tradition, such as the analytical a priori
      separation of research, policy and practice domains and the overemphasis on both
      the heterogeneity between domains and the homogeneity within these domains.
      Inductively developed insights from the field of science and technology studies
      (STS) show that the boundaries between research and policy are often much more
      fluid (and largely rhetorical) than the two communities tradition seems to
      acknowledge. What needs to be analysed is not only how the boundaries can be
      bridged, but how - and at what moments - these boundaries are maintained, redrawn
      or re-established - and for what purposes. This paper focuses on these questions
      by utilizing the alternative conceptual framework of coproduction. It draws on
      long term qualitative research to structural collaborations (the Dutch Academic
      Collaborative Centres for Public Health) to illustrate these points. 

PMID- 24854763
TI  - Chimerin 2 genetic polymorphisms are associated with non-proliferative diabetic
      retinopathy in Taiwanese type 2 diabetic patients.
AB  - AIM: To investigate whether chimerin 2 (CHN2) genetic polymorphisms were
      associated with the susceptibility to diabetic retinopathy (DR) in Taiwanese
      individuals with type 2 diabetes. METHODS: This case-control study comprised of
      171 individuals with DR and 548 without DR. Four rs39059, rs2023908, rs1002630
      and rs1362363 polymorphism of CHN2 were genotyped for each subjects. All subjects
      underwent a complete ophthalmologic examination, and basic information (age,
      gender, age at diagnosis of diabetes, and ocular history of the patient) was
      record. Several clinical parameters (systolic and diastolic blood pressure, waist
      and hip circumferences, body mass index levels, fasting glucose and HbA1c) were
      measured. RESULTS: Logistic regressions were used to analyze odds ratios between
      SNPs and DR after controlling for gender, systolic blood pressure, waist and hip
      ratio, duration of diabetes, serum HbA1c levels and nephropathy classification. A
      protective effect of rs1002630 (GA+AA) and rs1362363 (AG+GG) [odds ratio (OR)
      (95% confidence interval)=0.45 (0.22-0.88), 0.66 (0.44-0.99), respectively) was
      observed. Furthermore, the protective effect of rs1002630 was observed when
      compared subjects with non-proliferative DR with subjects without DR [OR=0.25
      (95%C.I. = 0.09-0.73)]. CONCLUSIONS: This study showed that the rs1002630 of CHN2
      were associated with DR risk and non-proliferative DR risk in Taiwanese
      individuals with type 2 diabetes. Variations at this locus may contribute to the
      pathogenesis of DR.

PMID- 24854765
TI  - RBRDetector: improved prediction of binding residues on RNA-binding protein
      structures using complementary feature- and template-based strategies.
AB  - Computational prediction of RNA-binding residues is helpful in uncovering the
      mechanisms underlying protein-RNA interactions. Traditional algorithms
      individually applied feature- or template-based prediction strategy to recognize
      these crucial residues, which could restrict their predictive power. To improve
      RNA-binding residue prediction, herein we propose the first integrative algorithm
      termed RBRDetector (RNA-Binding Residue Detector) by combining these two
      strategies. We developed a feature-based approach that is an ensemble learning
      predictor comprising multiple structure-based classifiers, in which well-defined
      evolutionary and structural features in conjunction with sequential or structural
      microenvironment were used as the inputs of support vector machines. Meanwhile,
      we constructed a template-based predictor to recognize the putative RNA-binding
      regions by structurally aligning the query protein to the RNA-binding proteins
      with known structures. The final RBRDetector algorithm is an ingenious fusion of
      our feature- and template-based approaches based on a piecewise function. By
      validating our predictors with diverse types of structural data, including bound
      and unbound structures, native and simulated structures, and protein structures
      binding to different RNA functional groups, we consistently demonstrated that
      RBRDetector not only had clear advantages over its component methods, but also
      significantly outperformed the current state-of-the-art algorithms. Nevertheless,
      the major limitation of our algorithm is that it performed relatively well on DNA
      binding proteins and thus incorrectly predicted the DNA-binding regions as RNA
      binding interfaces. Finally, we implemented the RBRDetector algorithm as a user
      friendly web server, which is freely accessible at
      http://ibi.hzau.edu.cn/rbrdetector.

PMID- 24854764
TI  - Effects of acclimation salinity on the expression of selenoproteins in the
      tilapia, Oreochromis mossambicus.
AB  - Selenoproteins are ubiquitously expressed, act on a variety of physiological
      redox-related processes, and are mostly regulated by selenium levels in animals.
      To date, the expression of most selenoproteins has not been verified in
      euryhaline fish models. The Mozambique tilapia, Oreochromis mossambicus, a
      euryhaline cichlid fish, has a high tolerance for changes in salinity and
      survives in fresh water (FW) and seawater (SW) environments which differ greatly
      in selenium availability. In the present study, we searched EST databases for
      cichlid selenoprotein mRNAs and screened for their differential expression in FW
      and SW-acclimated tilapia. The expression of mRNAs encoding iodothyronine
      deiodinases 1, 2 and 3 (Dio1, Dio2, Dio3), Fep15, glutathione peroxidase 2,
      selenoproteins J, K, L, M, P, S, and W, was measured in the brain, eye, gill,
      kidney, liver, pituitary, muscle, and intraperitoneal white adipose tissue. Gene
      expression of selenophosphate synthetase 1, Secp43, and selenocysteine lyase,
      factors involved in selenoprotein synthesis or in selenium metabolism, were also
      measured. The highest variation in selenoprotein and synthesis factor mRNA
      expression between FW- and SW-acclimated fish was found in gill and kidney. While
      the branchial expression of Dio3 was increased upon transferring tilapia from SW
      to FW, the inverse effect was observed when fish were transferred from FW to SW.
      Protein content of Dio3 was higher in fish acclimated to FW than in those
      acclimated to SW. Together, these results outline tissue distribution of
      selenoproteins in FW and SW-acclimated tilapia, and indicate that at least Dio3
      expression is regulated by environmental salinity. 

PMID- 24854766
TI  - Tuning of the copper-thioether bond in tetradentate N3S(thioether) ligands; O-O
      bond reductive cleavage via a [Cu(II)2(MU-1,2-peroxo)]2+/[Cu(III)2(MU-oxo)2]2+
      equilibrium.
AB  - Current interest in copper/dioxygen reactivity includes the influence of
      thioether sulfur ligation, as it concerns the formation, structures, and
      properties of derived copper-dioxygen complexes. Here, we report on the chemistry
      of {L-Cu(I)}2-(O2) species L = (DMM)ESE, (DMM)ESP, and (DMM)ESDP, which are
      N3S(thioether)-based ligands varied in the nature of a substituent on the S atom,
      along with a related N3O(ether) (EOE) ligand. Cu(I) and Cu(II) complexes have
      been synthesized and crystallographically characterized. Copper(I) complexes are
      dimeric in the solid state, [{L-Cu(I)}2](B(C6F5)4)2, however are shown by
      diffusion-ordered NMR spectroscopy to be mononuclear in solution. Copper(II)
      complexes with a general formulation [L-Cu(II)(X)](n+) {X = ClO4(-), n = 1, or X
      = H2O, n = 2} exhibit distorted square pyramidal coordination geometries and
      progressively weaker axial thioether ligation across the series. Oxygenation (
      130  degrees C) of {((DMM)ESE)Cu(I)}(+) results in the formation of a trans-MU
      1,2-peroxodicopper(II) species [{((DMM)ESE)Cu(II)}2(MU-1,2-O2(2-))](2+) (1(P)).
      Weakening the Cu-S bond via a change to the thioether donor found in (DMM)ESP
      leads to the initial formation of [{((DMM)ESP)Cu(II)}2(MU-1,2-O2(2-))](2+) (2(P))
      that subsequently isomerizes to a bis-MU-oxodicopper(III) complex,
      [{((DMM)ESP)Cu(III)}2(MU-O(2-))2](2+) (2(O)), with 2(P) and 2(O) in equilibrium
      (K(eq) = [2(O)]/[2(P)] = 2.6 at -130  degrees C). Formulations for these Cu/O2
      adducts were confirmed by resonance Raman (rR) spectroscopy. This solution
      mixture is sensitive to the addition of methylsulfonate, which shifts the
      equilibrium toward the bis-MU-oxo isomer. Further weakening of the Cu-S bond in
      (DMM)ESDP or substitution with an ether donor in (DMM)EOE leads to only a bis-MU
      oxo species (3(O) and 4(O), respectively). Reactivity studies indicate that the
      bis-MU-oxodicopper(III) species (2(O), 3(O)) and not the trans-peroxo isomers
      (1(P) and 2(P)) are responsible for the observed ligand sulfoxidation. Our
      findings concerning the existence of the 2(P)/2(O) equilibrium contrast with
      previously established ligand-Cu(I)/O2 reactivity and possible implications are
      discussed.

PMID- 24854768
TI  - Highlighting Kathleen Green and Mario Delmar, guest editors of special issue
      (part 2): junctional targets of skin and heart disease.
AB  - Cell Communication and Adhesion has been fortunate to enlist two pioneers of
      epidermal and cardiac cell junctions, Kathleen Green and Mario Delmar, as Guest
      Editors of a two part series on junctional targets of skin and heart disease.
      Part 2 of this series begins with an overview from Dipal Patel and Kathy Green
      comparing epidermal desmosomes to cardiac area composita junctions, and surveying
      the pathogenic mechanisms resulting from mutations in their components in heart
      disease. This is followed by a review from David Kelsell on the role of
      desmosomal mutation in inherited syndromes involving skin fragility. Agnieszka
      Kobeliak discusses how structural deficits in the epidermal barrier intersect
      with the NFkB signaling pathway to induce inflammatory diseases such as psoriasis
      and atopic dermatitis. Farah Sheikh reviews the specialized junctional components
      in cardiomyocytes of the cardiac conduction system and Robert Gourdie discusses
      how molecular complexes between sodium channels and gap junction proteins within
      the perijunctional microdomains within the intercalated disc facilitate
      conduction. Glenn Radice evaluates the role of N-cadherin in heart. Andre Kleber
      and Chris Chen explore new approaches to study junctional mechanotransduction in
      vitro with a focus on the effects of connexin ablation and the role of cadherins,
      respectively. To complement this series of reviews, we have interviewed Werner
      Franke, whose systematic documentation the tissue-specific complexity of
      desmosome composition and pioneering discovery of the cardiac area composita
      junction greatly facilitated elucidation of the role of desmosomal components in
      the pathophysiology of human heart disease.

PMID- 24854769
TI  - Bringing law and order to the cytoskeleton and cell junctions: an interview with
      Werner Franke.

PMID- 24854767
TI  - The role of acupuncture in in vitro fertilization: a systematic review and meta
      analysis.
AB  - BACKGROUND/AIMS: In recent years, acupuncture has become more and more popular in
      the management of subfertility. The aim of this study was to evaluate the impact
      of acupuncture during in vitro fertilization (IVF) treatment on the outcomes of
      clinical pregnancy in published randomized studies. METHODS: This is a systematic
      review and meta-analysis. Data sources used were MEDLINE, Embase, Web of
      Knowledge and the Chinese Biomedical Database. RESULTS: There was no
      statistically significant difference between the acupuncture group and no
      acupuncture (intervention) controls around the time of embryo transfer (ET; risk
      ratio, RR, 1.24, 95% confidence interval, CI, 1.02-1.50) or in unblinded trials,
      trials blinded to physicians and double-blind trials (95% CI 1.26-1.88, 0.82-1.33
      and 0.89-1.25, respectively). This was also the case when comparing acupuncture
      with sham acupuncture controls around the time of ET (RR, 1.03, 95% CI 0.87-1.22)
      or when restricting to unblinded trials, trials blinded to physicians and double
      blind trials (95% CI 0.80-2.02, 0.82-1.18 and 0.77-1.17, respectively). There was
      a statistically significant difference when performed at 30 min after ET and
      implantation phase (RR 1.76, 95% CI 1.22-2.55). There was also a statistically
      significant difference when performed at follicle phase and 25 min before and
      after ET (RR 1.56, 95% CI 1.04-2.33). CONCLUSION: Our study showed that
      acupuncture did not significantly improve the IVF clinical pregnancy rate when
      performed only at the time of ET, while we found pooled benefit of acupuncture
      for IVF when performed at follicle phase and 25 min before and after ET, as well
      as 30 min after ET and implantation phase.

PMID- 24854770
TI  - Autofluorescence spectroscopy for NADH and flavoproteins redox state monitoring
      in the isolated rat heart subjected to ischemia-reperfusion.
AB  - BACKGROUND: Reduction of myocardial ischemia-reperfusion injury in the patients
      undergoing cardiac surgery under cardiopulmonary bypass represents an important
      goal. Intraoperative monitoring of myocardial metabolic state using continuous
      registration of nicotinamide adenine dinucleotide (NADH) and flavin adenine
      dinucleotide (FAD) fluorescence might contribute to the solution of the problem.
      The successful application of fluorescent spectroscopy in the clinical field
      requires additional refinement of the technique, particularly using excitation of
      both NADH and FAD with different wavelengths. METHODS: The experiments were
      performed on the isolated Langendorff-perfused rat hearts (n=28) subjected to
      either regional or global ischemia-reperfusion. Two principles of NADH and FAD
      autofluorescence (AF) measurement were used for ischemia monitoring: (1) analysis
      of photographs and videos obtained with multispectral organoscopy technique
      allowing the assessment of both spatial and temporal characteristics of the
      process (n=16); (2) continuous registration of tissue redox state in a
      representative area of the heart by application of local spectroscopy, assisted
      by fiber optic spectrometer (n=12). RESULTS: It was found that regional
      myocardial ischemia resulted in a rapid, substantial increase in the intensity of
      NADH AF excited at 360nm in the ischemic versus non-ischemic area of the heart.
      The same result was obtained when the heart was made globally ischemic, while the
      restoration of perfusate flow completely reversed the increase in NADH AF. During
      the transition from ischemia to reperfusion, the spatial heterogeneity of
      myocardial AF was noted on video recordings, probably reflecting the
      microheterogeneity of myocardial blood flow. Local spectroscopy studies
      demonstrated opposite changes in the NADH and FAD AF during ischemia. Using both
      methodological approaches, we found that repetitive brief episodes of global
      myocardial ischemia resulted in progressive decrease in the magnitude of AF
      elevation, which might point to preconditioning effect. CONCLUSIONS: The
      application of multispectral fluorescent organoscopy offers the advantage of
      monitoring myocardial redox state at the level of the entire heart. Local
      spectroscopy is characterized by better precision and, in addition, provides the
      unique opportunity to measure AF in different parts of the spectrum. AF
      measurements are non-invasive, rapid, and technically easy to perform. For future
      clinical applications, it might be recommended to combine the measurement of
      redox state of both NADH and FAD, using excitation wavelength and emission filter
      optimal for each fluorophore.

PMID- 24854771
TI  - Differentiating between comorbidity and symptom overlap in ADHD and early onset
      bipolar disorder.
AB  - Reported rates of comorbidity between early onset bipolar disorder (BD) and
      attention deficit hyperactivity disorder (ADHD) have a wide range, perhaps due to
      developmental issues and differences in interpretation of overlapping symptoms.
      We compared questionnaire-based and neuropsychological measures of inattention
      and impulsivity/hyperactivity, in children/adolescents with ADHD combined subtype
      (ADHD-C; n26), concurrent ADHD-C and BD (n15), BD (n25) with Controls (n69). Sub
      analyses were performed on BD with and without inattention symptoms. The two ADHD
      C groups displayed neuropsychological impairments that were not found in the BD
      group in spite of subjective and questionnaire-rated inattention. The findings
      caution against over-diagnosis of ADHD in BD. 

PMID- 24854773
TI  - Two-character Chinese compound word processing in Chinese children with and
      without dyslexia: ERP evidence.
AB  - Using event-related potential (ERP) measures, we examined the time course of
      Chinese compound word processing in 15 dyslexic and 10 normal children in a
      lexical decision task with three conditions including real words (e.g.,[Formula:
      see text] (house)), reversed nonwords (e.g.,[Formula: see text][Formula: see
      text] can be transposed to a real word [Formula: see text](ocean)) and random
      nonwords (e.g.,[Formula: see text] is not a real word when transposing).
      Behavioral results showed that dyslexic children performed slower and less
      accurately than normal children did across conditions. ERP data revealed that
      normal children exhibited significant N400 effects across conditions. The
      dyslexics did not show any difference on N400, however, suggesting a possible
      weakness of morphological processing in dyslexic children. 

PMID- 24854772
TI  - Carving the world for language: how neuroscientific research can enrich the study
      of first and second language learning.
AB  - Linguistics, psychology, and neuroscience all have rich histories in language
      research. Crosstalk among these disciplines, as realized in studies of phonology,
      is pivotal for understanding a fundamental challenge for first and second
      language learners (SLLs): learning verbs. Linguistic and behavioral research with
      monolinguals suggests that infants attend to foundational event components (e.g.,
      path, manner). Language then heightens or dampens attention to these components
      as children map word to world in language-specific ways. Cross-linguistic
      differences in semantic organization also reveal sources of struggles for SLLs.
      We discuss how better integrating neuroscience into this literature can unlock
      additional mysteries of verb learning. 

PMID- 24854774
TI  - Executive functions in preschool children with ADHD and DBD: an 18-month
      longitudinal study.
AB  - In this longitudinal study, we examined the stability of the association between
      executive functions and externalizing behavior problems, and the developmental
      change of executive functions in a predominately clinically diagnosed preschool
      sample (N = 200). Inhibition and working memory performance were assessed three
      times in 18 months. Across time, poorer inhibition performance in young children
      was associated with attention deficit hyperactivity disorder (ADHD) and
      disruptive behavior disorders (DBD), and poorer working memory performance was
      associated with ADHD. Inhibition and working memory performance increased over
      time, especially in the early preschool period. The improvement of inhibition
      performance was more pronounced in the clinically diagnosed children compared to
      the TD children. 

PMID- 24854775
TI  - Magnetoencephalographic signatures of numerosity discrimination in fetuses and
      neonates.
AB  - Numerosity discrimination has been demonstrated in newborns, but not in fetuses.
      Fetal magnetoencephalography allows non-invasive investigation of neural
      responses in neonates and fetuses. During an oddball paradigm with auditory
      sequences differing in numerosity, evoked responses were recorded and mismatch
      responses were quantified as an indicator for auditory discrimination. Thirty
      pregnant women with healthy fetuses (last trimester) and 30 healthy term neonates
      participated. Fourteen adults were included as a control group. Based on
      measurements eligible for analysis, all adults, all neonates, and 74% of fetuses
      showed numerical mismatch responses. Numerosity discrimination appears to exist
      in the last trimester of pregnancy. 

PMID- 24854777
TI  - ["Choosing the route of delivery": choose, you said choose?].

PMID- 24854776
TI  - [Providing of a virtual simulator perineal anatomy (Pelvic Mentor(r)) in learning
      pelvic perineology: results of a preliminary study].
AB  - INTRODUCTION: Medical and surgical simulation is in high demand. It is widely
      used in North America as a method of education and training of medical students
      and surgical residents. Learning anatomy and vaginal surgery are based on
      palpation recognition of different structures. The absence of visual control of
      actions learners is a limiting factor for the reproducibility of surgical
      techniques prolapse and urinary incontinenence. However, this reproducibility is
      the only guarantee of success and safety of these minimally invasive surgeries.
      METHODS: We evaluated the contribution of an educational module perineal anatomy
      using a system combining anatomic mannequin and a computerized 3D virtual
      simulator (Pelvic Mentor(r), Simbionix) in the knowledge of pelvic-perineal
      anatomical structures for eight residents of obstetrics and gynecology hospitals
      in Paris. RESULTS: The self-study training module has led to substantial
      improvements in internal rating with a proportion of structures recognized from
      31.25 to 87.5 % (P<0.001) for the front compartment and 20 to 85 % (P<0.001) for
      the posterior compartment. CONCLUSION: The preliminary results suggest that the
      3D virtual simulator enhances and facilitates learning the anatomy of the pelvic
      floor.

PMID- 24854778
TI  - A decreased mean platelet volume is associated with stable and exacerbated
      asthma.
AB  - BACKGROUND: Systemic inflammation is related to disease progression in asthma.
      Activated platelets play a critical role in atherogenesis, inflammation, and
      atherothrombosis. The mean platelet volume (MPV) is an early marker of platelet
      activation. OBJECTIVES: The aim of this study is to clarify the relevance of MPV
      levels in patients with stable and exacerbated asthma. METHODS: We investigated
      the peripheral blood cell count parameters, C-reactive protein (CRP), lung
      function parameters, and arterial blood gas in patients with asthma and control
      subjects. Eighty-five stable asthma patients and 85 asthmatics with exacerbations
      were investigated. Eighty-five controls matched for age, gender, body mass index
      (BMI), and smoking status were recruited. RESULTS: Patients with exacerbated
      asthma had lower MPV and higher CRP levels and white blood cell (WBC) counts
      compared to patients with stable asthma and control subjects. Furthermore, the
      MPV was reduced in patients with stable asthma compared to control subjects.
      Negative correlations between MPV and CRP were present in stable and exacerbated
      asthma. Although there was no relationship between MPV and WBC count in stable
      asthma, there was an inverse relationship between MPV and WBC count in
      exacerbated asthma. CONCLUSIONS: These findings show that patients with stable
      asthma had a lower MPV compared to controls and the MPV levels in asthmatic
      patients with exacerbations were lower compared to those in patients with stable
      asthma. Further investigations regarding the role of MPV in asthma may be
      beneficial in the search for therapeutic targets.

PMID- 24854779
TI  - Reporting sexual assault in the military: who reports and why most servicewomen
      don't.
AB  - BACKGROUND: Public and congressional attention to the Department of Defense's
      (DoD's) efforts to prevent and respond to sexual assault in the military (SAIM)
      is increasing. To promote reporting, the DoD offers (1) restricted reporting,
      allowing confidential reporting to designated military personnel without
      triggering an official investigation, and (2) unrestricted reporting, which
      initiates a criminal investigation. PURPOSE: To identify factors associated with
      officially reporting SAIM by examining demographic, military, and sexual assault
      characteristics and survey reporting perceptions and experiences. Differences
      between active component (AC) (full-time active duty) and Reserve and National
      Guard (RNG) were explored. METHODS: A Midwestern community sample of currently
      serving and veteran servicewomen (1,339) completed structured telephone
      interviews. RNG interviews were conducted March 2010 to September 2010 and AC
      interviews from October 2010 to December 2011. Data were analyzed in 2013.
      Logistic regression analyses examined demographic, military, and SA
      characteristics related to SAIM reporting. Bivariate statistics tested
      differences between AC and RNG. RESULTS: A total of 205 servicewomen experienced
      SAIM and 25% reported. More AC servicewomen experienced SAIM, but were no more
      likely to report than RNG servicewomen. Restricted reporting was rated more
      positively, but unrestricted reporting was used more often. Reporters'
      experiences corroborated non-reporters' concerns of lack of confidentiality,
      adverse treatment by peers, and beliefs that nothing would be done. Officers were
      less likely to report than enlisted servicewomen. CONCLUSIONS: Actual and
      perceived reporting consequences deter servicewomen from reporting. SAIM
      undermines trust in military units, mission readiness, and the health and safety
      of all service members.

PMID- 24854780
TI  - Influenza vaccination of Michigan children by provider type, 2010-2011.
AB  - BACKGROUND: Influenza vaccination for all children aged 6 months to 18 years has
      been recommended since 2008 to prevent flu-related morbidity and mortality.
      However, 2010-2011 influenza vaccine coverage estimates show under-vaccination in
      children of all ages. We examined predictors of influenza vaccination in Michigan
      during the 2010-2011 influenza season. PURPOSE: To determine whether immunization
      provider type was associated with a child's influenza vaccination in Michigan and
      assess whether county-level factors were confounders of the association. METHODS:
      Influenza vaccinations reported to the Michigan Care Improvement Registry from
      the 2010-2011 influenza season were analyzed in 2012 to estimate ORs for the
      association between immunization provider type and influenza vaccination.
      RESULTS: Among 2,373,826 Michigan children aged 6 months through 17 years, 17%
      were vaccinated against influenza and lower vaccination rates were observed for
      public compared to private providers (13% vs 18%). In the unadjusted model,
      public providers had lower odds of vaccinating children compared to private
      providers (OR=0.60, 95% CI=0.60, 0.61). County-level factors, including
      percentage of families living below the poverty line, median household income,
      and percentage black race, were not shown to confound the association. In the
      adjusted models, public providers had lower odds of vaccinating children compared
      to private providers (OR=0.87, 95% CI=0.86, 0.88). CONCLUSIONS: Although a
      child's likelihood of influenza vaccination in Michigan varies by provider type,
      more effective strategies to improve influenza vaccination rates for all Michigan
      children are needed.

PMID- 24854781
TI  - Standardization of nasalance scores in normal Saudi speakers.
AB  - OBJECTIVE: The aims of this study were to obtain normative nasalance scores for a
      normal Saudi population with different ages and genders, to develop nasometric
      Arabic speech materials, and to make cross-linguistic comparison. SUBJECTS:
      Participants included 219 normal Saudi native monolingual Arabic speakers of
      different ages. Subjects were classified into four groups according to age and
      gender. Subjects did not have any history of oral, nasal, or velopharyngeal
      abnormality. METHODS: Arabic speech samples were developed to evaluate nasalance
      scores, which included syllables repetition, three oral sentences, three oro
      nasal sentences, and three nasal sentences. Nasalance data were obtained using
      Nasometer II-6400. RESULTS: Normative nasalance values were determined.
      Significant differences between the male and female children groups were noticed
      in many parameters. Nasalance scores were higher in adults, with significant
      differences between all groups. CONCLUSION: Normative nasalance scores for Saudi
      Arabic speakers have been developed for both adults and children. The Arabic
      speech materials developed in this study appear to be easy to use and applicable
      for different age groups.

PMID- 24854782
TI  - Stem cells: stressed HSCs choose death.

PMID- 24854783
TI  - Post-translational modifications: Lys33-linked ubiquitin in post-Golgi transport.

PMID- 24854784
TI  - RNA interference: nuclear Dicer makes the cut.

PMID- 24854790
TI  - The faces of Big Science.
AB  - Fifty years ago, academic science was a calling with few regulations or financial
      rewards. Today, it is a huge enterprise confronted by a plethora of bureaucratic
      and political controls. This change was not triggered by specific events or
      decisions but reflects the explosive 'knee' in the exponential growth that
      science has sustained during the past three-and-a-half centuries. Coming to terms
      with the demands and benefits of 'Big Science' is a major challenge for today's
      scientific generation. Since its foundation 50 years ago, the European Molecular
      Biology Organization (EMBO) has been of invaluable help in meeting this
      challenge.

PMID- 24854789
TI  - Cellular mechanisms and physiological consequences of redox-dependent signalling.
AB  - Reactive oxygen species (ROS), which were originally characterized in terms of
      their harmful effects on cells and invading microorganisms, are increasingly
      implicated in various cell fate decisions and signal transduction pathways. The
      mechanism involved in ROS-dependent signalling involves the reversible oxidation
      and reduction of specific amino acids, with crucial reactive Cys residues being
      the most frequent target. In this Review, we discuss the sources of ROS within
      cells and what is known regarding how intracellular oxidant levels are regulated.
      We further discuss the recent observations that reduction-oxidation (redox)
      dependent regulation has a crucial role in an ever-widening range of biological
      activities - from immune function to stem cell self-renewal, and from
      tumorigenesis to ageing. 

PMID- 24854791
TI  - Robustness study of the different immittance spectra and frequency ranges in
      bioimpedance spectroscopy analysis for assessment of total body composition.
AB  - The estimation of body fluids is a useful and common practice for assessment of
      disease status and therapy outcomes. Electrical bioimpedance spectroscopy (EBIS)
      methods are noninvasive, inexpensive and efficient alternatives for determination
      of body fluids. One of the main source of errors in EBIS measurements in the
      estimation of body fluids is capacitive coupling. In this paper an analysis of
      capacitive coupling in EBIS measurements was performed and the robustness of the
      different immittance spectra against it tested. On simulations the conductance
      (G) spectrum presented the smallest overall error, among all immittance spectra,
      in the estimation of the impedance parameters used to estimate body fluids.
      Afterwards the frequency range of 10-500 kHz showed to be the most robust band of
      the G spectrum. The accuracy of body fluid estimations from the resulting
      parameters that utilized G spectrum and parameters provided by the measuring
      device were tested on EBIS clinical measurements from growth hormone replacement
      therapy patients against estimations performed with dilution methods. Regarding
      extracellular fluid, the correlation between each EBIS method and dilution was
      0.93 with limits of agreement of 1.06 +/- 2.95 l for the device, 1.10 +/- 2.94 l
      for G [10-500 kHz] and 1.04 +/- 2.94 l for G [5-1000 kHz]. Regarding
      intracellular fluid, the correlation between dilution and the device was 0.91,
      same as for G [10-500 kHz] and 0.92 for G [5-1000 kHz]. Limits of agreement were
      0.12 +/- 4.46 l for the device, 0.09 +/- 4.45 for G [10-500 kHz] and 0.04 +/-
      4.58 for G [5-1000 kHz]. Such close results between the EBIS methods validate the
      proposed approach of using G spectrum for initial Cole characterization and
      posterior clinical estimation of body fluids status. 

PMID- 24854788
TI  - The amyloid state and its association with protein misfolding diseases.
AB  - The phenomenon of protein aggregation and amyloid formation has become the
      subject of rapidly increasing research activities across a wide range of
      scientific disciplines. Such activities have been stimulated by the association
      of amyloid deposition with a range of debilitating medical disorders, from
      Alzheimer's disease to type II diabetes, many of which are major threats to human
      health and welfare in the modern world. It has become clear, however, that the
      ability to form the amyloid state is more general than previously imagined, and
      that its study can provide unique insights into the nature of the functional
      forms of peptides and proteins, as well as understanding the means by which
      protein homeostasis can be maintained and protein metastasis avoided. 

PMID- 24854793
TI  - Facile Preparation of a Thiol-Reactive (18)F-Labeling Agent and Synthesis of
      (18)F-DEG-VS-NT for PET Imaging of a Neurotensin Receptor-Positive Tumor.
AB  - Accumulating evidence suggests that neurotensin receptors (NTRs) play key roles
      in cancer growth and survival. In this study, we developed a simple and efficient
      method to radiolabel neurotensin peptide with (18)F for NTR-targeted imaging.
      METHODS: The thiol-reactive reagent (18)F-(2-(2-(2
      fluoroethoxy)ethoxy)ethylsulfonyl)ethane ((18)F-DEG-VS) was facilely prepared
      through 1-step radiofluorination. After high-pressure liquid chromatography
      purification, (18)F-DEG-VS was incubated with the c(RGDyC) and c(RGDyK) peptide
      mixture to evaluate its specificity toward the reactive thiol. Thiolated
      neurotensin peptide was then labeled with (18)F using this novel synthon, and the
      resulting imaging probe was subjected to receptor-binding assay and small-animal
      PET studies in a murine xenograft model. The imaging results and metabolic
      stability of (18)F-DEG-VS-NT were compared with the thiol-specific maleimide
      derivative N-[2-(4-(18)F-fluorobenzamido)ethyl]maleimide-neurotensin ((18)F-FBEM
      NT). RESULTS: (18)F-DEG-VS was obtained in high labeling yield. The reaction of
      (19)F-DEG-VS was highly specific for thiols at neutral pH, whereas the lysine of
      c(RGDyK) reacted at a pH greater than 8.5. (18)F-DEG-VS-c(RGDyC) was the
      preferred product when both c(RGDyK) and c(RGDyC) were incubated together with
      (18)F-DEG-VS. Thiolated neurotensin peptide (Cys-NT) efficiently reacted with
      (18)F-DEG-VS, with a 95% labeling yield (decay-corrected). The radiochemical
      purity of the (18)F-DEG-VS-NT was greater than 98%, and the specific activity was
      about 19.2 +/- 4.3 TBq/mmol. Noninvasive small-animal PET demonstrated that (18)F
      DEG-VS-NT had an NTR-specific tumor uptake in subcutaneous HT-29 xenografts. The
      tumor-to-muscle, tumor-to-liver, and tumor-to-kidney ratios reached 30.65 +/-
      22.31, 11.86 +/- 1.98, and 1.91 +/- 0.43 at 2 h after injection, respectively,
      based on the biodistribution study. Receptor specificity was demonstrated by
      blocking experiment. Compared with (18)F-FBEM-NT, (18)F-DEG-VS-NT was synthesized
      with fewer steps and provided significantly improved imaging quality in vivo.
      CONCLUSION: We have established a facile (18)F-labeling method for site-specific
      labeling of the Cys-NT. Using this method, we synthesized an NTR-targeted PET
      agent, which demonstrated high tumor-to-background contrast.

PMID- 24854794
TI  - Diversification in the Supply Chain of (99)Mo Ensures a Future for (99m)Tc.
AB  - The uncertain availability of (99m)Tc has become a concern for nuclear medicine
      departments across the globe. An issue for the United States is that currently it
      is dependent on a supply of (99m)Tc (from (99)Mo) that is derived solely by
      production outside the United States. Since the United States uses half the
      world's (99)Mo production, the U.S. (99)Mo supply chain would be greatly enhanced
      if a producer were located within the United States. The fragility of the old
      (99)Mo supply chain is being addressed as new facilities are constructed and new
      processes are developed to produce (99)Mo without highly enriched uranium. The
      conversion to low-enriched uranium is necessary to minimize the potential misuse
      of highly enriched uranium in the world for nonpeaceful means. New production
      facilities, new methods for the production of (99)Mo, and a new generator elution
      system for the supply of (99m)Tc are currently being pursued. The progress made
      in all these areas will be discussed, as they all highlight the need to embrace
      diversity to ensure that we have a robust and reliable supply of (99m)Tc in the
      future.

PMID- 24854792
TI  - Comparison of the Hypoxia PET Tracer (18)F-EF5 to Immunohistochemical Marker EF5
      in 3 Different Human Tumor Xenograft Models.
AB  - The availability of (18)F-labeled and unlabeled 2-(2-nitro-1H-imidazol-1-yl)-N
      (2,2,3,3,3-pentafluoropropyl)-acetamide (EF5) allows for a comparative assessment
      of tumor hypoxia by PET and immunohistochemistry; however, the combined use of
      these 2 approaches has not been fully assessed in vivo. The aim of this study was
      to evaluate (18)F-EF5 tumor uptake versus EF5 binding and hypoxia as determined
      from immunohistochemistry at both macroscopic and microregional levels. METHODS:
      Three tumor models-PC3, HCT116, and H460-were evaluated. Tumor-bearing animals
      were coinjected with (18)F-EF5 and EF5 (30 mg/kg), and PET imaging was performed
      at 2.5 h after injection. After PET imaging and 2 min after Hoechst 33342
      injection, the tumors were excised and evaluated for (18)F-EF5 distribution by
      autoradiography and EF5 binding by immunohistochemistry. Additionally, the
      effects of nonradioactive EF5 (30 mg/kg) on the hypoxia-imaging characteristics
      of (18)F-EF5 were evaluated by comparing the PET data for H460 tumors with those
      from animals injected with (18)F-EF5 alone. RESULTS: The uptake of (18)F-EF5 in
      hypoxic tumor regions and the spatial relationship between (18)F-EF5 uptake and
      EF5 binding varied among tumors. H460 tumors showed higher tumor-to-muscle
      contrast in PET imaging; however, the distribution and uptake of the tracer was
      less specific for hypoxia in H460 than in HCT116 and PC3 tumors. Correlation
      analyses revealed that the highest spatial correlation between (18)F-EF5 uptake
      and EF5 binding was in PC3 tumors (r = 0.73 +/- 0.02) followed by HCT116 (r =
      0.60 +/- 0.06) and H460 (r = 0.53 +/- 0.10). Uptake and binding of (18)F-EF5 and
      EF5 correlated negatively with Hoechst 33342 perfusion marker distribution in the
      3 tumor models. Image contrast and heterogeneous uptake of (18)F-EF5 in H460
      tumors was significantly higher when the radiotracer was used alone versus in
      combination with unlabeled EF5 (tumor-to-muscle ratio of 2.51 +/- 0.33 vs. 1.71
      +/- 0.17, P < 0.001). CONCLUSION: The uptake and hypoxia selectivity of (18)F-EF5
      varied among tumor models when animals also received nonradioactive EF5. Combined
      use of radioactive and nonradioactive EF5 for independent assessment of tumor
      hypoxia by PET and immunohistochemistry methods is promising; however, the EF5
      drug concentrations that are required for immunohistochemistry assays may affect
      the uptake of (18)F-EF5 in hypoxic cells in certain tumor types as observed in
      H460 in this study.

PMID- 24854797
TI  - Strongly veined carbon nanoleaves as a highly efficient metal-free
      electrocatalyst.
AB  - Effective integration of one-dimensional carbon nanofibers (CNF) and two
      dimensional carbon sheets into three-dimensional (3D) conductive frameworks is
      essential for their practical applications as electrode materials. Herein, a
      novel "vein-leaf"-type 3D complex of carbon nanofibers with nitrogen-doped
      graphene (NG) was prepared through a simple thermal condensation of urea and
      bacterial cellulose. During the formation of the 3D complex CNF@NG, the graphene
      species was tethered to CNF via carbon-carbon bonds. Such an interconnected 3D
      network facilitates both the electron transfer and mass diffusion for
      electrochemical reactions. 

PMID- 24854798
TI  - Impaired glycemia and Alzheimer's disease.

PMID- 24854795
TI  - An Improved Antagonist Radiotracer for the kappa-Opioid Receptor: Synthesis and
      Characterization of (11)C-LY2459989.
AB  - The kappa-opioid receptors (KORs) are implicated in several neuropsychiatric
      diseases and addictive disorders. PET with radioligands provides a means to image
      the KOR in vivo and investigate its function in health and disease. The purpose
      of this study was to develop the selective KOR antagonist (11)C-LY2459989 as a
      PET radioligand and characterize its imaging performance in nonhuman primates.
      METHODS: LY2459989 was synthesized and assayed for in vitro binding to opioid
      receptors. Ex vivo studies in rodents were conducted to assess its potential as a
      tracer candidate. (11)C-LY2459989 was synthesized by reaction of its iodophenyl
      precursor with (11)C-cyanide, followed by partial hydrolysis of the resulting
      (11)C-cyanophenyl intermediate. Imaging experiments with (11)C-LY2459989 were
      performed in rhesus monkeys with arterial input function measurement. Imaging
      data were analyzed with kinetic models to derive in vivo binding parameters.
      RESULTS: LY2459989 is a full antagonist with high binding affinity and
      selectivity for KOR (0.18, 7.68, and 91.3 nM, respectively, for kappa, MU, and
      delta receptors). Ex vivo studies in rats indicated LY2459989 as an appropriate
      tracer candidate with high specific binding signals and confirmed its KOR binding
      selectivity in vivo. (11)C-LY2459989 was synthesized in high radiochemical purity
      and good specific activity. In rhesus monkeys, (11)C-LY2459989 displayed a fast
      rate of peripheral metabolism. Similarly, (11)C-LY2459989 displayed fast uptake
      kinetics in the brain and an uptake pattern consistent with the distribution of
      KOR in primates. Pretreatment with naloxone (1 mg/kg, intravenously) resulted in
      a uniform distribution of radioactivity in the brain. Further, specific binding
      of (11)C-LY2459989 was dose-dependently reduced by the selective KOR antagonist
      LY2456302 and the unlabeled LY2459989. Regional binding potential values derived
      from the multilinear analysis-1 (MA1) method, as a measure of in vivo specific
      binding signal, were 2.18, 1.39, 1.08, 1.04, 1.03, 0.59, 0.51, and 0.50,
      respectively, for the globus pallidus, cingulate cortex, insula, caudate,
      putamen, frontal cortex, temporal cortex, and thalamus. CONCLUSION: The novel PET
      radioligand (11)C-LY2459989 displayed favorable pharmacokinetic properties, a
      specific and KOR-selective binding profile, and high specific binding signals in
      vivo, thus making it a promising PET imaging agent for KOR.

PMID- 24854799
TI  - Frequency of the ASP620ASN mutation in VPS35 and Arg1205His mutation in EIF4G1 in
      familial Parkinson's disease from South Italy.
AB  - Parkinson's disease (PD) is characterized by progressive loss of dopaminergic
      neurons in the substantia nigra pars compacta. This degeneration leads to
      bradykinesia, muscular rigidity, resting tremor, and postural instability. It
      affects 1%-2% of the population above the age of 60 years. Recently, 2 studies
      identified the Asp620Asn mutation in the vacuolar protein sorting 35 (VPS35)
      gene, and the Arg1205His in the eukaryotic translation initiation factor 4 gamma
      1 gene (EIF4G1) were reported to be associated an autosomal dominant form of PD.
      In this study we screened these mutations in a cohort of 250 South Italy patients
      with familial PD and 250 control subjects from South Italy. VPS35 Asp620Asn
      mutation and EIF4G1 Arg1205His mutation were not found in our 250 PD patients.
      This result, with our previous reports on the absence of mutations in LRRK2 and
      in SNCA, warrant a continuing search for novel causative genes for PD among South
      Italy. 

PMID- 24854800
TI  - Validity and reliability of the behavior rating inventory of executive function -
      adult version in a clinical sample with eating disorders.
AB  - This study is a preliminary investigation of the reliability and validity of the
      Behavior Rating Inventory of Executive Function - Adult Version (BRIEF-A) in a
      clinical sample of patients with eating disorders (ED). Participants were 252
      adult females who were referred to a centre for the treatment of EDs, as well as
      31 individuals who completed the informant version of the BRIEF-A. Patients
      completed the BRIEF-A and other psychological measures on one occasion during
      their initial clinic visit, and informants nominated by patients completed the
      informant version at home. Reliability analyses revealed high internal
      consistency (Cronbach's alpha) of the two indices (Metacognition Index and
      Behavioral Regulation Index), and for the Global Executive Composite (GEC) of the
      BRIEF-A (alpha = .96). Convergent validity was shown by a high positive
      relationship between the self-report and informant-report versions of the BRIEF
      A, and between the GEC and the Anxiety and Depression scales. Construct validity
      was assessed by an exploratory and confirmatory factor analysis. The BRIEF-A may
      be a reliable and valid tool for measuring executive functioning (EF) in an ED
      population, and may serve as an initial screening tool of EF for clinicians and
      researchers.

PMID- 24854801
TI  - Menopause and metabolic syndrome in obese individuals with binge eating disorder.
AB  - Menopausal transition has been associated with the emergence of metabolic
      abnormalities, which may increase risk for chronic medical conditions in women.
      This study compared metabolic function between premenopausal women (n = 152),
      postmenopausal women (n = 88), and men (n =9 8) recruited for treatment studies
      for obesity co-occurring with binge eating disorder (BED), a high-risk population
      for developing metabolic syndrome (MetS). Postmenopausal women were more likely
      than premenopausal women to show elevated total cholesterol (OR = 2.75; 95% CI =
      1.56-4.80) and poor glycemic control (OR = 2.92; 95% CI = 1.32-6.33) but were
      more likely to have lower HDL levels (OR = 0.36; 95% CI = 0.19-0.68). These
      became non-significant after adjusting for age. Both pre- and postmenopausal
      women were less likely than age-matched men to show elevated levels of
      triglycerides (OR = 0.27; 95% CI = 0.13-0.53 [postmenopausal], OR = 0.29; 95% CI
      = 0.16-0.53 [premenopausal]), blood pressure (OR = 0.48; 95% CI = 0.25-0.91
      [postmenopausal], OR=0.40; 95% CI = 0.23-0.69 [premenopausal]), and less likely
      to have MetS (OR = 0.41; 95% CI = 0.21-0.78 [postmenopausal], OR = 0.46; 95% CI =
      0.27-0.79 [premenopausal]). Premenopausal women were also less likely to have
      elevated fasting glucose level (OR = 0.50; 95% CI = 0.26-0.97) than age-matched
      men. Among obese women with BED, aging may have a more profound impact on
      metabolic abnormalities than menopause, suggesting the importance of early
      intervention of obesity and symptoms of BED. The active monitoring of metabolic
      function in obese men with BED may also be critical.

PMID- 24854802
TI  - Night eating behavior and metabolic heath in mothers and fathers enrolled in the
      QUALITY cohort study.
AB  - BACKGROUND: Desynchrony between eating and sleeping patterns and poor sleep
      quality have been associated with obesity and metabolic abnormalities. This study
      examined the metabolic health correlates of night eating syndrome in adults
      enrolled in the QUALITY cohort study. METHODS: Night eating symptoms were
      assessed in 310 women (mean age = 40.3 +/- 5.1 years, mean BMI = 28.8 +/- 6.2
      kg/m(2)) and 305 men (mean age = 42.5 +/- 5.9 years, mean BMI = 30.3 +/- 5.0
      kg/m(2)). Anthropometric measures, fasting blood samples and blood pressure were
      used to diagnose metabolic syndrome (MetS) and type 2 diabetes (T2D) diagnosis
      was self-report. Correlational and case/control comparisons assessed night eating
      symptoms in persons with and without MetS and T2D. RESULTS: Night eating
      questionnaire (NEQ) scores were positively correlated with BMI. When controlling
      for BMI, NEQ scores were significantly negatively correlated with blood pressure
      in women and positively correlated with waist circumference and triglycerides in
      men. MetS diagnosis was associated with morning anorexia in both women and men
      and urges to eat at night in women only. T2D was associated with a depressed mood
      in women and with insomnia in men. CONCLUSION: Symptoms of night eating syndrome
      are associated with higher BMI and poor metabolic health. Future research is
      needed to determine if night eating syndrome per se is a unique causal pathway in
      the development of obesity and metabolic disease.

PMID- 24854803
TI  - Course and moderators of emotional eating in anorectic and bulimic patients: a
      follow-up study.
AB  - Emotion dysregulation has been found to be associated with specific eating
      attitudes and behavior in Eating Disorder (ED) patients. The present study
      evaluated whether emotional eating profile of ED patients changes over time and
      the possible effects of a psychotherapeutic intervention on the emotional eating
      dimension. One hundred and two ED patients (28 with Anorexia Nervosa restricting
      type [AN-R], 35 with Anorexia Nervosa binge/purging subtype [AN-B/P] and 39 with
      Bulimia Nervosa [BN]) were evaluated at baseline, at the end of a Cognitive
      Behavioral Therapy, at 3 and 6 year follow-up. The Structured Clinical Interview
      for DSM IV Axis I Disorders, the Emotional Eating Scale (EES) and several self
      reported questionnaires for eating specific and general psychopathology were
      applied. A control group of 86 healthy subjects was also studied, in order to
      compare psychopathological variables at baseline. A significant EES total score
      reduction was observed among AN-B/P and BN patients, whereas no significant
      change was found in the AN-R group. Mixed Models analyses showed that a
      significant effect on EES total score variation was found for cocaine or
      amphetamine abuse (b = .25; p < .01). Patients who assumed these substances
      reported no significant EES reduction across time, unlike other patients. The
      present results suggest that ED patients with a history of cocaine or amphetamine
      abuse represent a sub-population of patients with lasting dysfunctional mood
      modulatory mechanisms.

PMID- 24854804
TI  - Mindfulness meditation as an intervention for binge eating, emotional eating, and
      weight loss: a systematic review.
AB  - Mindfulness-based approaches are growing in popularity as interventions for
      disordered eating and weight loss. Initial research suggests that mindfulness
      meditation may be an effective intervention for binge eating; however, no
      systematic review has examined interventions where mindfulness meditation was the
      primary intervention and no review has examined its effect on subclinical
      disordered eating or weight. Using the PRISMA method for systematic reviews, we
      reviewed 14 studies that investigated mindfulness meditation as the primary
      intervention and assessed binge eating, emotional eating, and/or weight change.
      Results suggest that mindfulness meditation effectively decreases binge eating
      and emotional eating in populations engaging in this behavior; evidence for its
      effect on weight is mixed. Additional research is warranted to determine
      comparative effectiveness and long-term effects of mindfulness training. 

PMID- 24854805
TI  - Disordered eating links to body-relevant and body-irrelevant influences on self
      evaluation.
AB  - We investigated eating- and weight-related correlates of self-evaluation
      influences (SEIs) and examined the extent to which such SEIs can be both over-
      and undervalued and the extent to which measurement strategy affects SEIs. A
      female undergraduate sample (n = 549) completed 3 measures of SEI importance and
      questionnaires assessing disordered eating (DE), body mass index (BMI), and
      depression. SEI measures included Likert scale, rank ordering, and pairwise
      forced choice; a subset (n = 62) also completed the Shape- and Weight-Based Self
      Esteem Scale (SAWBS). Only rank ordering, forced choice, and SAWBS constrain
      choices among SEIs, such that prioritizing one SEI necessarily deprioritizes
      another, which reflects real-world restrictions on individuals' allotment of time
      and energy (e.g., spending hours exercising daily necessarily reduces time
      available for other activities). By any measure, women with DE overvalue body
      shape and weight. The constraining measures reveal systematic undervaluation of
      intelligence and achievement among women with DE and an enhanced effect of DE on
      the overvaluation of weight and on the undervaluation of being a good person
      among those with higher BMI. Depressed women's self-evaluations overemphasize
      appearance and underemphasize interpersonal relationships. Self-evaluations of
      women with DE are marked by both over- and undervaluation of relevant SEIs; the
      overvaluation of shape and weight in DE may be associated with costs. Future use
      of constraining measures, such as forced choice or rank ordering, may enhance our
      understanding of both over- and underemphasized SEIs among women with DE.

PMID- 24854806
TI  - The development and validation of the Physical Appearance Comparison Scale
      Revised (PACS-R).
AB  - The Physical Appearance Comparison Scale (PACS; Thompson, Heinberg, & Tantleff,
      1991) was revised to assess appearance comparisons relevant to women and men in a
      wide variety of contexts. The revised scale (Physical Appearance Comparison Scale
      Revised, PACS-R) was administered to 1176 college females. In Study 1,
      exploratory factor analysis and parallel analysis using one half of the sample
      suggested a single factor structure for the PACS-R. Study 2 utilized the
      remaining half of the sample to conduct confirmatory factor analysis, item
      analysis, and to examine the convergent validity of the scale. These analyses
      resulted in an 11-item measure that demonstrated excellent internal consistency
      and convergent validity with measures of body satisfaction, eating pathology,
      sociocultural influences on appearance, and self-esteem. Regression analyses
      demonstrated the utility of the PACS-R in predicting body satisfaction and eating
      pathology. Overall, results indicate that the PACS-R is a reliable and valid tool
      for assessing appearance comparison tendencies in women. 

PMID- 24854807
TI  - Flexibility in weight management.
AB  - The purpose of the study was to investigate the relationships between changes in
      flexible vs. rigid restraints of eating during weight management, as well as how
      changes in the cognitive restraint of eating were related to psychological well
      being and flexibility. The data includes information on 49 overweight persons who
      participated in a weight loss and maintenance (WLM) intervention and a follow-up
      assessment after 8-9 months. An increase in flexible cognitive restraint during
      the weight loss intervention was related to better weight loss maintenance and
      well-being. The more flexible restraint increased during the WLM intervention,
      the more psychological distress decreased. Moreover, larger reduction of rigid
      restraint during the follow-up period (between the WLM intervention and the
      follow-up assessment) was related to a better maintenance of improved
      psychological well-being at the follow-up endpoint. These results suggest that
      increasing flexible control while reducing rigid control of eating after an
      active weight loss phase improves success in weight management and the
      psychological well-being of weight losers.

PMID- 24854808
TI  - Parent skills training to enhance weight loss in overweight children: evaluation
      of NOURISH.
AB  - OBJECTIVE: Although there is general agreement that parents should be involved in
      pediatric obesity treatment, few studies have investigated the effectiveness of
      interventions that target parents exclusively. Moreover, the effectiveness of
      this approach has not been adequately assessed with racially diverse families,
      particularly African Americans(AA), a group at high risk for elevated Body Mass
      Index (BMI). METHODS: NOURISH (Nourishing Our Understanding of Role modeling to
      Improve Support and Health) is a culturally-sensitive parenting intervention
      targeting overweight (AA) children (ages 6-11; MBMI = 98.0%ile). Families (N =
      84; 61% AA, 37% White) were randomly assigned to NOURISH or a control group.
      RESULTS: NOURISH families significantly improved on child BMI from pre- to post
      testing after adjustment for random effects, baseline BMI, and child race.
      NOURISH parents were very satisfied with the intervention and would recommend it
      to other parents; 91% strongly or moderately agreed that NOURISH helped them eat
      in a healthier manner. CONCLUSIONS: These pilot data suggest that NOURISH is
      acceptable and, with refinement, offers promise for reducing pediatric BMI.
      Outcomes, lessons learned, and parent feedback will inform a larger randomized
      controlled trial.

PMID- 24854809
TI  - Looking at food in sad mood: do attention biases lead emotional eaters into
      overeating after a negative mood induction?
AB  - BACKGROUND: Emotional eating is associated with overeating and the development of
      obesity. Yet, empirical evidence for individual (trait) differences in emotional
      eating and cognitive mechanisms that contribute to eating during sad mood remain
      equivocal. AIM: The aim of this study was to test if attention bias for food
      moderates the effect of self-reported emotional eating during sad mood (vs
      neutral mood) on actual food intake. It was expected that emotional eating is
      predictive of elevated attention for food and higher food intake after an
      experimentally induced sad mood and that attentional maintenance on food predicts
      food intake during a sad versus a neutral mood. METHOD: Participants (N = 85)
      were randomly assigned to one of the two experimental mood induction conditions
      (sad/neutral). Attentional biases for high caloric foods were measured by eye
      tracking during a visual probe task with pictorial food and neutral stimuli. Self
      reported emotional eating was assessed with the Dutch Eating Behavior
      Questionnaire (DEBQ) and ad libitum food intake was tested by a disguised food
      offer. RESULTS: Hierarchical multivariate regression modeling showed that self
      reported emotional eating did not account for changes in attention allocation for
      food or food intake in either condition. Yet, attention maintenance on food cues
      was significantly related to increased intake specifically in the neutral
      condition, but not in the sad mood condition. DISCUSSION: The current findings
      show that self-reported emotional eating (based on the DEBQ) might not validly
      predict who overeats when sad, at least not in a laboratory setting with healthy
      women. Results further suggest that attention maintenance on food relates to
      eating motivation when in a neutral affective state, and might therefore be a
      cognitive mechanism contributing to increased food intake in general, but maybe
      not during sad mood.

PMID- 24854810
TI  - The role of trait and ability emotional intelligence in bulimic symptoms.
AB  - Bulimia is characterized by poor affect regulation, yet the role of emotional
      intelligence (EI) is little understood. This study examined associations between
      EI and bulimic symptoms using 235 women from community and student populations.
      They completed measures of trait and ability EI, and the Eating Disorders
      Diagnostic Scale. Results showed that deficiencies in different aspects of trait
      EI and/or ability EI are a function of symptom type: binge eating, compensatory
      behaviours or weight and shape concerns. Consistent with affect regulation
      models, self-regulatory aspects of trait EI were related to two bulimic symptoms:
      binge eating and weight and shape concerns. Ability-based self-emotion management
      was not important, and explanatory power of lower-level EI facets (traits or
      abilities) was not superior to more broadly defined EI factors. Results support
      the conclusion that trait and ability EI may maintain subclinical levels of
      bulimic symptoms but have different paths. 

PMID- 24854811
TI  - Binge eating frequency and regular eating adherence: the role of eating pattern
      in cognitive behavioral guided self-help.
AB  - Cognitive behavioral guided self-help (CBTgsh) is an evidence-based, brief, and
      cost-effective treatment for eating disorders characterized by recurrent binge
      eating. However, more research is needed to improve patient outcomes and clarify
      treatment components most associated with symptom change. A main component of
      CBTgsh is establishing a regular pattern of eating to disrupt dietary
      restriction, which prior research has implicated in the maintenance of binge
      eating. The present study used session-by-session assessments of regular eating
      adherence and weekly binge totals to examine the association between binge
      frequency and regular eating in a sample of participants (n = 38) receiving 10
      sessions of CBTgsh for recurrent binge eating. Analyses were conducted using
      Hierarchical Linear Modeling (HLM) to allow for data nesting, and a likelihood
      ratio test determined which out of three regression models best fit the data.
      Results demonstrated that higher regular eating adherence (3 meals and 2-3
      planned snacks daily) was associated with lower weekly binge frequency in this
      sample, and both the magnitude and direction of the association were maintained
      after accounting for individual participant differences in binge and adherent day
      totals. Findings provide additional empirical support for the cognitive
      behavioral model informing CBTgsh. Possible clinical implications for treatment
      emphasis and sequencing in CBTgsh are discussed.

PMID- 24854813
TI  - Risk eating behaviors in male and female students: a longitudinal study.
AB  - The purpose of this research was to analyze changes in body mass index and risk
      eating behaviors in a group of students through a longitudinal study and
      determine the differences in risk eating behaviors between men and women with
      different rates of body mass. 5780 students participated, 37.5% were male and
      62.5% female, mean age for each measurement times were: 15.1 years first
      measurement, 18.0 yearssecond measurement, 22.1 years last measurement. For
      purposes of this study indicators were used from automated medical examination,
      which serves to collect information on the physical and mental health, family and
      environment of students at a public university in Mexico. The measurements were
      made for weight and height of each student to then calculate the body mass index
      based on the proposal of the World Health Organization. Risk eating behaviors
      were evaluated with seven indicators that measure the presence or absence of such
      things as: the use of laxatives, vomiting after eating, exercising 2 h a day,
      stop eating for a day or moreover, use of pills or diuretics, being on more than
      two. Significant differences were found in the risk eating behavior with respect
      to different categories of body mass index only in the first measurement, where
      young people were of less underweight risk eating behavior than those who are
      overweight.

PMID- 24854812
TI  - The prediction role of indexes of circulating adipokines for common
      anthropometric and nutritional characteristics of obesity in the obese Central
      European population.
AB  - AIMS: This study was designed to investigate the relationship between 8 selected
      adipokines (leptin, leptin receptor, adiponectin, agouti-related peptide,
      omentin, visfatin, adipsin and resistin), dietary composition and anthropometric
      parameters found in the Central European obese population. METHODS: A total of 65
      unrelated obese Central European Caucasian individuals were recruited for the
      study. Phenotypic measurements included weight, height, BMI, lean body mass, fat
      mass, body fat, waist and hip circumference, waist-hip ratio (WHR) and skinfold
      thickness. Participants completed standardized self-reported 7-day food records.
      Plasma levels of leptin, leptin receptor, adiponectin, agouti-related peptide
      (AgRP), resistin, adipsin, omentin and visfatin were examined using ELISA.
      RESULTS: Multiple associations (weight, height, percentage of body fat, waist
      circumference, hip circumference, WHR and sum of skinfold thickness) with the
      circulation levels of the investigated adipokines were identified. Leptin-Leptin
      receptor (L-LR) levels were found to correlate with total energy intake and
      macronutrients while adipsin was found to strongly correlate with multiple
      adipokines. Furthermore, the L-LR index was found to constitute a more accurate
      description of the relationship between BMI and body weight than individual
      measurements and the Ag-LR index was found to strongly correlate with both
      anthropometric and dietary characteristics. CONCLUSION: Following confirmation on
      larger population samples and on samples of different ethnicities, the reported
      adipokine indexes could become a useful tool for estimating nutritional status
      and predicting the body composition of specific patient groups.

PMID- 24854814
TI  - The role of anxiety sensitivity in daily physical activity and eating behavior.
AB  - Anxiety sensitivity (AS), or the fear of somatic arousal, has been linked to both
      maladaptive eating behavior as well as exercise avoidance in both self-report and
      laboratory-based experiments. The current pilot study sought to extend these
      finding to the naturalistic setting. A sample of 32 adults completed affect and
      dietary monitoring and wore actigraphs across a three-day monitoring period.
      Results indicated that high AS was associated with greater calorie consumption
      overall in women and less consumption in men, and high AS predicted an increase
      in calories consumed following participants' greatest increase in negative affect
      in both sexes. For physical activity, results indicated an AS by BMI interaction
      such that obese individuals with high AS engaged in less moderate-intensity
      physical activity, whereas the opposite was true for normal weight individuals.
      These results indicate that AS may represent a double-edged risk factor for
      obesity contributing to both exercise avoidance and calorie consumption. 

PMID- 24854815
TI  - Overvaluation of shape and weight as a mediator between self-esteem and weight
      bias internalization among patients with binge eating disorder.
AB  - OBJECTIVE: This study aimed to evaluate the roles of self-esteem and
      overvaluation of shape and weight in accounting for the internalization of weight
      bias among patients with binge eating disorder (BED) and obesity. METHOD: Two
      hundred forty-five treatment-seeking individuals with BED and obesity were
      evaluated with diagnostic and semi-structured interviews and completed the Weight
      Bias Internalization Scale (WBIS) and the Rosenberg Self-Esteem Scale (RSE).
      Correlations and bootstrapping mediation analyses were computed to evaluate the
      relationships among self-esteem, overvaluation of shape/weight, and weight bias
      internalization. The effects of body mass index (BMI) and binge-eating frequency
      were also tested. RESULTS: Significant correlations emerged between WBIS, RSE,
      and overvaluation of shape and weight. BMI did not correlate with any measure,
      and binge-eating frequency only correlated with overvaluation. Mediation analyses
      provided support for the hypothesis that overvaluation of shape and weight
      mediates the relationship between self-esteem and weight bias internalization.
      DISCUSSION: These findings provide support to the proposed model that self-esteem
      and overvaluation of shape and weight contribute to weight bias internalization
      among patients with BED, which holds implications for clinical efforts to address
      weight bias and associated eating and weight-related psychopathology.

PMID- 24854816
TI  - Focusing on media body ideal images triggers food intake among restrained eaters:
      a test of restraint theory and the elaboration likelihood model.
AB  - Although research consistently shows that images of thin women in the media
      (media body ideals) affect women negatively (e.g., increased weight
      dissatisfaction and food intake), this effect is less clear among restrained
      eaters. The majority of experiments demonstrate that restrained eaters -
      identified with the Restraint Scale - consume more food than do other
      participants after viewing media body ideal images; whereas a minority of
      experiments suggest that such images trigger restrained eaters' dietary
      restraint. Weight satisfaction and mood results are just as variable. One reason
      for these inconsistent results might be that different methods of image exposure
      (e.g., slideshow vs. film) afford varying levels of attention. Therefore, we
      manipulated attention levels and measured participants' weight satisfaction and
      food intake. We based our hypotheses on the elaboration likelihood model and on
      restraint theory. We hypothesised that advertent (i.e., processing the images via
      central routes of persuasion) and inadvertent (i.e., processing the images via
      peripheral routes of persuasion) exposure would trigger differing degrees of
      weight dissatisfaction and dietary disinhibition among restrained eaters (cf.
      restraint theory). Participants (N = 174) were assigned to one of four
      conditions: advertent or inadvertent exposure to media or control images. The
      dependent variables were measured in a supposedly unrelated study. Although
      restrained eaters' weight satisfaction was not significantly affected by either
      media exposure condition, advertent (but not inadvertent) media exposure
      triggered restrained eaters' eating. These results suggest that teaching
      restrained eaters how to pay less attention to media body ideal images might be
      an effective strategy in media-literary interventions.

PMID- 24854817
TI  - Relationships between depression, gender, and unhealthy weight loss practices
      among overweight or obese college students.
AB  - INTRODUCTION: Unhealthy weight loss practices are common among female college
      students. It is unknown if these practices are also most common among women in
      the subset of overweight or obese college students or if these practices are
      related to depression. We examined the relationship between gender, depression,
      and unhealthy weight loss practices among overweight or obese college students.
      METHODS: Students (body mass index between 25.0 and 34.9 kg/m(2)) from three
      Southern California universities (M(age) = 22 years, SD = 4; 70% women) were
      recruited from May 2011 to May 2012 for participation in a weight loss clinical
      trial (N = 404). Logistic regressions were performed with baseline data to assess
      the cross-sectional relationship between self-reported unhealthy weight loss
      practices and gender and depression as measured by the Center for Epidemiologic
      Studies Depression short form. RESULTS: Twenty-nine percent of participants
      reported engaging in at least one unhealthy weight loss behavior (e.g., fasting,
      purging) over the last 30 days, with no differences by gender. Self-report of at
      least one unhealthy weight loss behavior was associated with report of symptoms
      of depression (e(B) = 1.14 [confidence interval, CI: 1.08-1.20]), adjusting for
      potential confounders. Interactions between gender and depression were not
      significant (e(B) = 1.04 [CI: 0.93-1.16]). CONCLUSION: Among an overweight or
      obese sample of college students, unhealthy weight loss practices were equally
      common in both genders, and students with depressive symptomatology were at
      greatest risk. Obesity interventions targeting overweight or obese college
      students should educate both men and women about the dangers of unhealthy weight
      loss practices. In addition, screening for depression can help identify students
      who would benefit from additional supportive and coping strategies and resources.

PMID- 24854819
TI  - Tests of an extension of the dual pathway model of bulimic symptoms to the state
      based level.
AB  - The dual pathway model proposes that trait body dissatisfaction leads to bulimic
      symptoms via two distinct pathways: dieting and trait negative affect. As many of
      these modelled variables have state-based equivalents, the present study
      evaluated the generalisability of this model to predict associations between
      state body dissatisfaction and instances of disordered eating. 124 women aged 18
      to 40 years completed an online survey (accessed via a mobile phone device with
      web access) over a 7-day period. The mobile phone device prompted participants at
      random intervals seven times daily to self-report their state body
      dissatisfaction, current mood experiences, dieting attempts, and disordered
      eating practices. Multi-level mediation modelling revealed that both negative
      mood states and dieting significantly mediated the state body dissatisfaction
      disordered eating relationships, although the strength of these associations
      depended on the aspect of disordered eating measured and individual differences
      in trait body dissatisfaction, internalization of appearance standards, tendency
      towards dieting, and BMI. Collectively, these results not only support adapting
      the dual pathway model to the state-level, but also suggest that several of the
      model implied pathways may be more relevant for individuals with more
      pathological eating- and body-related concerns and behaviours.

PMID- 24854818
TI  - Developmental trends of eating disorder symptoms and comorbid internalizing
      symptoms in children and adolescents.
AB  - OBJECTIVE: To determine when gender differences in disordered eating symptoms
      emerge, when correlations between disordered eating and internalizing symptoms
      develop, and whether the relationship between internalizing and disordered eating
      symptoms varies based on age and/or gender. METHOD: We used questionnaire data
      from a community sample (N = 424) of third, sixth, and ninth grade girls and
      boys. RESULTS: Gender differences in eating pathology emerge between 12 and 15
      years. The relationship between anxiety symptoms and eating pathology among both
      genders is weak and remains constant between the third and ninth grades. The
      relationship between depressive symptoms and eating pathology increases between
      the third and sixth grades for boys, and the sixth and ninth grades for girls.
      CONCLUSION: Before age 12, prevention programs for eating disorders should be
      given to both genders, whereas after age 12, they should target girls. Further,
      providers should offer intervention for comorbid depressive symptoms by third
      grade for boys and sixth grade for girls.

PMID- 24854821
TI  - Disordered eating partly mediates the relationship between poor sleep quality and
      high body mass index.
AB  - OBJECTIVE: We evaluated the relationship between poor sleep quality and high body
      mass index (BMI) in a community-derived sample. In addition, we explored the
      premise that disordered eating (i.e. eating late at night and/or binge eating,
      which can occur at night) may partly explain the relationship. METHOD: An online
      survey asked 330 participants about their height and weight, recent sleep
      quality, and recent experiences of binge-eating and night-time eating. RESULTS:
      Using multiple regression analyses, high BMI was shown to be related to shorter
      sleep duration, increased sleep latency, use of sleeping medications and worse
      binge-eating, whereas worse sleep quality was related to worse night-eating,
      after controlling for depression and demographics. Using mediational analyses,
      binge-eating was shown to partly mediate the relationship between worse sleep
      quality to higher BMI, whereas night-eating mediated the reverse association of
      high BMI to worse sleep quality. DISCUSSION: The results suggest that night-
      and/or binge-eating may partly explain the observed relationship between worse
      sleep quality and overweight/obesity. Thus, the relationship may simply reflect
      that overweight people are more likely to binge-eat while they wait for sleep to
      come, and this may contribute to weight gain over time. In addition, the results
      may indicate that eating rather than weight gain or obesity may be responsible
      for causing the sleep deficits in overweight people.

PMID- 24854820
TI  - Sex differences in the association between dietary restraint, insulin resistance
      and obesity.
AB  - BACKGROUND & AIMS: Restrained food consumption may alter metabolic function and
      contribute to eventual weight gain; however, sex differences in these
      relationships have not been assessed. The objective of this study was to examine
      the relationship between restrained eating and insulin resistance and the
      influence of body mass index and sex on this relationship in a large community
      sample of both men and women. We hypothesized that restrained eating would be
      related to insulin resistance and this relationship would be influenced by sex
      and body mass index. METHODS: In this cross-sectional, observational study, we
      studied 487 individuals from the community (men N = 222, women N = 265), who
      ranged from lean (body mass index 18.5-24.9 kg/m(2), N = 173), overweight (body
      mass index 25-29.9 kg/m(2), N = 159) to obese (body mass index >30 kg/m(2), N =
      155) weight categories. We assessed restrained eating using the Dutch Eating
      Behavior Questionnaire and obtained fasting morning plasma insulin and glucose on
      all subjects. RESULTS: In men, but not in women, restrained eating was related to
      homeostatic model assessment of insulin resistance (HOMA-IR) (p < 0.0001).
      Furthermore, HOMA-IR was significantly higher in men who were high- versus low
      restrained eaters (p = 0.0006). CONCLUSIONS: This study is the first to report
      sex differences with regard to the relationship between restrained eating and
      insulin resistance. Our results suggest that high restrained eating is associated
      with insulin resistance in men but not in women.

PMID- 24854822
TI  - Which facets of mindfulness are related to problematic eating among patients
      seeking bariatric surgery?
AB  - There has been growing research indicating the potential positive benefits of
      mindfulness-based interventions for obesity, but few studies have examined the
      relationship of mindfulness processes to obesity-related behaviors, particularly
      among clinical populations such as bariatric surgery candidates. The current
      study examined the relationship of specific mindfulness facets to a variety of
      problematic eating behaviors assessed through diagnostic interviews in a clinical
      sample of 820 patients seeking bariatric surgery. Results indicated that greater
      mindfulness on specific facets, particularly acting with awareness, was related
      to less binge and emotional eating. Greater mindfulness was also related, though
      less consistently, to less habitual overeating and grazing. The observing facet
      was generally unrelated to problematic eating, but in a few cases being more
      observant related to having greater eating problems. The results of the study and
      future directions are discussed in relation to research on problematic eating in
      obesity and mindfulness-based interventions. 

PMID- 24854823
TI  - Disordered eating & cultural diversity: a focus on Arab Muslim women in Israel.
AB  - CONTEXT: A dearth of data concerning eating problems among adult women from
      minority population groups leaves substantial knowledge gaps and constrains
      evidence-based interventions. OBJECTIVES: To examine prevalence and predictors of
      disordered eating behaviors (DEB) among Arab Muslim women in Israel, whose eating
      behaviors have not been previously examined and to compare with second generation
      Israeli-born Jews of European heritage. DESIGN: Community-based study includes
      sub-samples of Arab Muslims and Israeli-born Jews. DEB is assessed with fourteen
      DSM-IV related symptoms. Hierarchical regressions examine influence of weight,
      self-criticism and psychological distress on DEB severity. RESULTS: Relatively
      high prevalence rates emerge for Muslims (27%) and Jews (20%), a nonsignificant
      difference. In contrast, regressions reveal substantially different predictor
      patterns. For Arab Muslims, weight has the strongest association; for Jews,
      weight is not significant while self-criticism is the strongest predictor.
      Explained variance also differs considerably: 45% for Muslims and 28% for Jews.
      CONCLUSIONS: Surprising similarities and distinct differences underscore complex
      patterns of eating disturbances across culturally diverse groups. Culturally
      sensitive interventions are warranted along with more illuminating explanatory
      paradigms than 'one size fits all.'

PMID- 24854824
TI  - Biting versus chewing: eating style and social aggression in children.
AB  - Does biting food lead to aggressive behavior? An experimental study is reported
      where children ages 6-10 (n = 12) were served chicken either on-the-bone or pre
      cut in bite-size pieces. When children ate on-the-bone chicken, they exhibited
      more aggressive behavior than pre-cut, boneless chicken. For example, children
      were more likely to violate the counselor's instructions by leaving the eating
      area after eating on-the-bone chicken compared to kids who ate pre-cut chicken.
      These findings suggest a connection between how children eat and how they behave.
      This could have implications for developmental psychologists as well as for
      educators and parents.

PMID- 24854825
TI  - Exploring child-feeding style in childcare settings: how might nursery
      practitioners affect child eating style and weight?
AB  - Although considerable research has explored the role of parents in affecting
      child eating habits and weight, there has been little consideration of the impact
      of other key care providers in the early years. A controlling maternal child
      feeding style (e.g. use of pressure to eat or restricting certain foods) has been
      associated with over consumption, fussy eating and weight issue. Conversely,
      responsive child-feeding styles whereby children are allowed to regulate their
      own intake but encouraged to eat a range of foods and try new tastes are
      associated with healthier eating styles and weight. Increasing numbers of
      preschool children now spend time in day care settings, many for up to fifty
      hours a week but interactions with caregivers during mealtimes remain unexplored.
      The aim of the current study was to begin to explore child-feeding styles of
      nursery practitioners working with children aged 0-5 years. Sixty three nursery
      practitioners completed an adapted version of the Child Feeding Questionnaire to
      examine their interactions with children during mealtimes. Themes included
      pressure to eat, encouragement to eat and use of reward. Typically practitioners
      reported responsive child-feeding styles with low levels of pressure to eat but
      high levels of encouragement to try new foods. Use of reward to eat certain foods
      or as a bribe to modify behaviour was however more common. The findings have
      important implications for understanding the role of childcare providers in
      affecting child eating habits and weight.

PMID- 24854826
TI  - Dispelling myths about a new healthful food can be more motivating than promoting
      nutritional benefits: the case of Tofu.
AB  - OBJECTIVE: This study examines what factors impact the adoption of certain types
      of healthy foods, such as Tofu, by future nutritional gatekeepers. DESIGN:
      Information on perceived facilitators and barriers to the utilization of barriers
      would be obtained via interviews and surveys. SETTING: In-depth laddering
      interviews and an online survey during 2012 were utilized. SUBJECTS: The in-depth
      laddering interviews were conducted with 83 young women and new mothers (non
      vegetarians and non-Asians) who were enthusiastic lovers of Tofu. 502 women from
      the target demographic (between 20 and 35, non-Asian) were recruited from a
      national panel and surveyed online in 2012. RESULTS: Based on the interviews, 21
      primary reasons for trying Tofu (facilitators) and 10 reasons that might be
      preventative (barriers) were identified. A key finding was that facilitators were
      not motivating factors for why women adopted Tofu into their diets. Instead,
      barriers explained more than 44% of the variance for not adopting tofu.
      CONCLUSIONS: When encouraging nutritional gatekeepers to add Tofu to their
      household diets, it may be more effective to focus on changing the barriers. This
      study suggests that nutritionists and health practitioners may be more successful
      in encouraging the adoption of healthy new foods by dispelling their
      misconceptions rather than focusing on their nutritional benefits.

PMID- 24854827
TI  - Associations among eating regulation and body mass index, weight, and body fat in
      college students: the moderating role of gender.
AB  - This study investigated associations between eating regulation behaviors and body
      mass index (BMI), weight, and percent body fat in male and female students over
      the first two years of college. Subjects included 328 college students (215
      females and 113 males). Height and weight (via standard techniques), body
      composition (via bioelectrical impedance analysis), and eating regulation
      behaviors (using the Regulation of Eating Behavior Scale) were conducted two to
      three times during both the freshman and sophomore years. Significant
      associations between eating regulation and BMI, weight, and/or percent body fat
      were shown mostly in females. In females, higher BMI, weight, and/or percent body
      fat at the end of the second year of college were found in those with low levels
      of autonomous, intrinsic motivation, and identified regulation, and high levels
      of amotivation, while lower BMI, weight, and/or percent body fat were associated
      with high levels of autonomous, intrinsic motivation, and identified regulation,
      and low levels of amotivation. The findings that specific eating behaviors in
      females during the first two years of college influence BMI, weight, and/or
      percent body fat may be useful for inclusion in university programs focused on
      college student health to help decrease the risk of obesity and disordered
      eating/eating disorders in female college students. 

PMID- 24854828
TI  - BMI, body discrepancy, and self-construal as predictors of eating disturbances in
      European and Asian American females.
AB  - This study examined for ethnic variations in the predictive utility of body
      discrepancy and self-construal in eating disturbances between 156 European
      American and 129 Asian American females. We found important ethnic variations in
      the prediction model between these two groups, especially in the value of self
      construal. Some implications of the present findings are discussed. 

PMID- 24854829
TI  - Occurrence of habituation during repeated food exposure via the olfactory and
      gustatory systems.
AB  - BACKGROUND: Greater exposure to an orosensory cue could increase habituation
      rate. This investigation examined salivary habituation during 10 lemon juice
      trials providing exposure via olfactory, gustatory, and combined systems.
      METHODS: Healthy, normal-weight, unrestrained females (age = 20.7 +/- 2.7 year,
      body mass index [BMI] = 22.2 +/- 1.5 kg/m(2), 70.0% white) were randomly assigned
      to 1 of 3 conditions: olfactory (SMELL: n = 8), gustatory (TASTE: n = 10), or
      olfactory+gustatory (SMELL+TASTE: n = 9). All conditions completed 12, 2-minute,
      trials (trials 1-2: water [baseline]; trials 3-12: lemon juice), in which
      salivation was measured. In conditions with taste exposure, 0.05 ml of the
      stimulus was placed on the tongue. In conditions with smell exposure, 4.0 g of
      the stimulus was held 0.5 in from the nose. Salivation was measured using dental
      rolls and mean salivation of every two trials was the dependent variable.
      RESULTS: A mixed-factor ANCOVA, controlling for baseline differences between the
      conditions in lemon juice hedonics, found a significant (p < 0.05) interaction of
      condition x trial. SMELL+TASTE significantly (p < 0.05) increased salivation from
      baseline to lemon juice exposure, and decreased salivation by the last two mean
      trials. TASTE had a significant (p < 0.05) increase in salivation from baseline
      to lemon juice, with no decrease. CONCLUSION: Repeated exposure to an orosensory
      cue by combined olfactory and gustatory systems produced a faster habituation
      rate than exposure by the gustatory system alone. Thus, food cues that combine
      exposure to the olfactory and gustatory systems may enhance satiation.

PMID- 24854832
TI  - Incorporating a new 2H-[1,2,3]triazolo[4,5-c]pyridine moiety to construct D-A-pi
      A organic sensitizers for high performance solar cells.
AB  - Two new organic dyes (PTN1 and NPT1) of the configuration D-A-pi-A, based on 2H
      [1,2,3]triazolo[4,5-c]pyridine (PT) as a central linker, have been synthesized
      and used as the sensitizers for dye-sensitized solar cells. Compared with
      pyridal[2,1,3]thiadiazole-containing congeners, the new dyes have conversion
      efficiencies nearly 1 order higher due to alleviation of charge trapping. The
      best conversion efficiency of the cell reaches 6.05% (under AM 1.5G irradiation).
      Upon addition of the coadsorbent CDCA, the efficiency is boosted to 6.76%, which
      reaches ~90% of the standard based on N719. 

PMID- 24854830
TI  - Nonlinear analysis of saccade speed fluctuations during combined action and
      perception tasks.
AB  - BACKGROUND: Saccades are rapid eye movements used to gather information about a
      scene which requires both action and perception. These are usually studied
      separately, so that how perception influences action is not well understood. In a
      dual task, where the subject looks at a target and reports a decision, subtle
      changes in the saccades might be caused by action-perception interactions.
      Studying saccades might provide insight into how brain pathways for action and
      for perception interact. NEW METHOD: We applied two complementary methods,
      multifractal detrended fluctuation analysis and Lempel-Ziv complexity index to
      eye peak speed recorded in two experiments, a pure action task and a combined
      action-perception task. RESULTS: Multifractality strength is significantly
      different in the two experiments, showing smaller values for dual decision task
      saccades compared to simple-task saccades. The normalized Lempel-Ziv complexity
      index behaves similarly i.e. is significantly smaller in the decision saccade
      task than in the simple task. COMPARISON WITH EXISTING METHODS: Compared to the
      usual statistical and linear approaches, these analyses emphasize the character
      of the dynamics involved in the fluctuations and offer a sensitive tool for
      quantitative evaluation of the multifractal features and of the complexity
      measure in the saccades peak speeds when different brain circuits are involved.
      CONCLUSION: Our results prove that the peak speed fluctuations have multifractal
      characteristics with lower magnitude for the multifractality strength and for the
      complexity index when two neural pathways are simultaneously activated,
      demonstrating the nonlinear interaction in the brain pathways for action and
      perception.

PMID- 24854831
TI  - An efficient and reproducible method to culture Bergmann and cortical radial glia
      using textured PMMA.
AB  - BACKGROUND: Radial glia cells comprise the principal population of neural stem
      cells (NSC) during development. Attempts to develop reproducible radial glia and
      NSC culture methods have met with variable results, yielding non-adherent
      cultures or requiring the addition of growth factors. Recent studies demonstrated
      that a 2-MUm patterned poly-methyl methacrylate (ln2 PMMA) grooved scaffold, by
      mimicking the biophysical and microtopographic properties of the embryonic NSC
      niche, induces the de-differentiation of glial cells into functional radial glia
      cells. NEW METHOD: Here we describe a method for obtaining cultures of adherent
      Bergmann radial glia (BRG) and cortical radial glia (CRG). The growth substrate
      is ln2 PMMA and the addition of growth factors is not required. RESULTS:
      Postnatal glia obtained from mouse cerebellum or cerebral cortex and grown on ln2
      PMMA adopted a BRG/CRG phenotype characterized by a bipolar shape, the up
      regulation of progenitor markers such as nestin and Sox2, and the down-regulation
      of vimentin and GFAP. Neurons cultured over the BRG/CRG aligned their processes
      with those of the glial shafts, thus mimicking the behavior of migrating neuronal
      cells. COMPARISON WITH EXISTING METHODS: The ln2 PMMA culture method offers an
      ideal system for analyzing both the biochemical factors controlling the
      neurogenic potential of BRG/CRG and neuronal migration. CONCLUSIONS: The ln2 PMMA
      method is a reproducible system to obtain immature BRG/CRG preparations in vitro.
      It can be used to study the properties of CNS progenitor cells as well as the
      interactions between radial glia and neurons, and supports cultured progenitors
      for use in different applications.

PMID- 24854833
TI  - Performing in the surgical amphitheater of today: perception of urologists
      conducting live case demonstrations.
AB  - PURPOSE: To evaluate the perception of urologists who have participated in live
      case demonstrations (LCDs) regarding safety, educational value/benefits, and
      ethics. METHODS: A 19-question anonymous survey was sent to urologists who
      performed and/or moderated LCDs at the World Congress of Endourology meetings
      from 2008 to 2012. E-survey was distributed via e-mail, and automatic reminders
      were sent 2 weeks after original distribution if no response was obtained.
      RESULTS: Eighty-one percent (92/113) of the urologists responded to the survey of
      whom 75% practice full time in an academic setting. Only 48.0% were fellowship
      trained, however. More than 60% had performed more than five LCDs at their home
      and/or away institutions. Performing LCD at an away institution was associated
      with a higher level of anxiety when compared with performing LCDs at a home
      institution (79.8% vs 34.6%; P<0.01). Respondents considered film equipment and
      crew; audience and moderator discussions; unfamiliar team, instruments and tools;
      language barrier; and having to narrate the procedure, as distractors. Seventy
      nine percent considered LCD as an ethical practice, and 90.5% regarded LCDs as a
      "beneficial" and a "great way" to educate. Similarly, considering the various
      factors and conditions associated with LCDs, 95% would agree to participate in
      another LCD. CONCLUSION: LCDs are perceived to be an effective mode of education
      by performers and moderators of LCDs. Standard guidelines and policies are
      needed, however, for the selection of patient, surgeon and team, equipment, and
      facility. Studies are needed to evaluate the impact of this education process.

PMID- 24854834
TI  - Design rules for efficient transgene expression in plants.
AB  - Sustained expression of transgenes in specified developmental patterns is
      commonly needed in plant biotechnology, but obstructed by transgene silencing.
      Here, we present a set of gene design rules, tested on the silencing-susceptible
      beetle luc and bacterial ims genes, expressed in sugarcane. Designs tested
      independently or in combination included removal of rare codons, removal of RNA
      instability sequences, blocking of likely endogenous sRNA binding sites and
      randomization of non-rare codons. Stable transgene expression analyses, on
      multiple independent lines per construct, showed greatest improvement from the
      removal of RNA instability sequences, accompanied by greatly reduced transcript
      degradation evident in northern blot analysis. We provide a set of motifs that
      readily can be eliminated concurrently with rare codons and undesired structural
      features such as repeat sequences, using Gene Designer 2.0 software. These design
      rules yielded 935- and 5-fold increased expression in transgenic callus, relative
      to the native luc and ims sequences; and gave sustained expression under the
      control of sugarcane and heterologous promoters over several years in greenhouse
      and field trials. The rules can be applied easily with codon usage tables from
      any plant species, providing a simple and effective means to achieve sustained
      expression of otherwise silencing-prone transgenes in plants. 

PMID- 24854835
TI  - Effect of induced acute diabetes and insulin therapy on stratum corneum barrier
      function in rat skin.
AB  - BACKGROUND: A wide variety of cutaneous manifestations are associated with
      diabetes. However, there is a paucity of information on stratum corneum barrier
      function in diabetics, with and without insulin therapy. METHODS: To assess for
      alteration of the stratum corneum, its barrier function was tested by evaluating
      the percutaneous absorption of water, ethanol, lidocaine and hydrocortisone, in
      vitro, on normal control, 4-week diabetic and 8-day insulin-treated diabetic
      Sprague-Dawley CD rats. RESULTS: Total water penetration was not different
      between the 3 groups though flux profiles were different. Both total penetration
      and peak flux of lidocaine and hydrocortisone increased slightly in the diabetic
      rats over the control group. However, total penetration and peak flux (including
      ethanol) were significantly increased in the insulin-treated rats. CONCLUSION:
      The data indicate that diabetes modestly alters stratum corneum physiology but
      less so than that seen following insulin therapy.

PMID- 24854836
TI  - The complex clinical picture of benzodiazepine misuse.

PMID- 24854837
TI  - Ca3Be6B5O16F: the first alkaline-earth beryllium borate with fluorine anions.
AB  - The first all-alkaline-earth beryllium borate with fluorine anions, Ca3Be6B5O16F,
      was synthesized by a spontaneous crystallization flux method using LiF-B2O3 as
      the flux. The structural framework of Ca3Be6B5O16F is composed of the inter
      connected [Be6B3O16] and [BO3] fundamental building blocks, with [CaO7F]
      distorted polyhedra located in the interstitial sites. The [Be6B3O16] group is
      discovered for the first time in beryllium borates. The UV-Vis-NIR diffuse
      reflectance spectrum demonstrates that its UV cutoff edge is below 200 nm, and
      this is confirmed by first-principles studies. Thermal analysis reveals an
      incongruent feature at 1321 K. IR spectroscopy measurements are consistent with
      the crystallographic study. These data reveal that the crystal could have an
      application as a deep-ultraviolet optical material. 

PMID- 24854838
TI  - Celecoxib enhances radiosensitivity via induction of G2-M phase arrest and
      apoptosis in nasopharyngeal carcinoma.
AB  - BACKGROUND: Previous work has proposed that celecoxib may be able to enhance the
      effects of radiotherapy. However, the underlying mechanism of this activity has
      not yet been determined. METHODS: The cell colony formation assay after the
      combination of celecoxib and radiation treatment was done on C666-1, CNE-1 and
      CNE-2 nasopharyngeal carcinoma cells, which expressed different COX-2 levels.
      Moreover, COX-2 knocked down or overexpressed cells were developed, and apoptosis
      and cell cycle analysis were performed. RESULTS: Celecoxib enhances radiation
      cytotoxicity in C666-1 and CNE-1 nasopharyngeal carcinoma cells that expressed
      high COX-2 but not in CNE-2 cells that expressed low COX-2. The
      radiosensitization of celecoxib in C666-1 cells disappeared after the COX-2
      knocked down, while the CNE-2 cells were radiosensitized by celecoxib after the
      transfection of COX-2. Moreover, celecoxib enhanced radiation-induced G2-M phase
      arrest was observed in some of the tested cells. Furthermore, we found that the
      radiosensitivity of celecoxib in nasopharyngeal carcinoma was correlated with the
      apoptosis induction. Additionally, the combination of celecoxib (25 mg/kg) and
      radiation (6 Gy) treatment significantly reduced tumor volume in C666-1 and CNE-2
      nasopharyngeal carcinoma xenograft models. CONCLUSION: These results indicate
      that the combination of celecoxib and radiation treatment has potential
      application in radiotherapy, and these effects may be attributable to the G2-M
      cell phase arrest and enhancement of cell apoptosis.

PMID- 24854839
TI  - Enhancing hepatic fatty acid oxidation as a strategy for reversing metabolic
      disorders programmed by maternal undernutrition during gestation.
AB  - BACKGROUND/AIMS: Moderate maternal calorie-restriction during gestation
      programmes offspring for a major propensity to develop metabolic alterations in
      adulthood. We aimed to assess whether increased hepatic fatty-acid oxidation
      (FAO), at early ages, by gene transfer of Cpt1am (active mutant of carnitine
      palmitoyltransferase-1a), may be a strategy for reversing metabolic disturbances
      associated to maternal calorie-restriction during gestation in rats. METHODS: AAV
      Gfp (control) and AAV-Cpt1am vectors were administered by tail vein injection in
      18-day-old control-pups and the offspring of 20% calorie-restricted rats during
      gestation (CR). After weaning, animals were fed with normal-fat diet. At the age
      of 4 months, they were moved to HF-diet and sacrificed at the age of 6 months to
      collect tissues. Locomotive activity, energy expenditure and blood pressure were
      measured. RESULTS: Under HF-diet, CR-animals showed higher HOMA-IR, adipocyte
      diameter and hepatic triglyceride accumulation than controls; these alterations
      were reverted in Cpt1am-injected animals. In liver, this treatment ameliorated
      inflammatory state, decreased expression of lipogenesis-related genes and
      partially restored the decreased expression of leptin-receptor occurring in CR
      animals. Treatment also reverted the decreased energy expenditure and the
      increased blood pressure of CR-animals. CONCLUSION: Increasing hepatic FAO
      through AAV-Cpt1am injection at juvenile ages prevents some metabolic disorders
      associated to gestational maternal calorie-restriction.

PMID- 24854840
TI  - Stimulation of erythrocyte cell membrane scrambling by mitotane.
AB  - background: Mitotane (1,1-dichloro-2-[o-chlorophenyl]-2-[p-chlorophenyl]ethane),
      a cytostatic drug used for the treatment of adrenocortical carcinomas, is
      effective by triggering tumor cell apoptosis. In analogy to apoptosis of
      nucleated cells, eryptosis is the suicidal death of erythrocytes, which is
      typically paralleled by cell shrinkage and breakdown of cell membrane
      phosphatidylserine asymmetry with subsequent phosphatidylserine exposure at the
      erythrocyte surface. Eryptosis may be triggered by increase of cytosolic Ca(2+)
      concentration ([Ca(2+)]i). The present study tested, whether treatment of human
      erythrocytes with mitotane is followed by eryptosis. METHODS: [Ca(2+)]i was
      estimated from Fluo3 fluorescence, cell volume from forward scatter,
      phosphatidylserine exposure from annexin V binding, and hemolysis from hemoglobin
      release. RESULTS: Exposure to mitotane (>= 5 ug/ml ~ 16 uM) significantly
      increased [Ca(2+)]i, increased annexin V binding and triggered hemolysis, but did
      not significantly modify forward scatter. The effect on annexin V binding was
      significantly blunted in the absence of extracellular Ca(2+). Within 30 min
      Ca(2+) ionophore ionomycin (1 uM) decreased forward scatter, an effect virtually
      abolished in the presence of mitotane (15 ug/ml). CONCLUSIONS: Mitotane increases
      [Ca(2+)]i with subsequent phosphatidylserine translocation. By the same token
      mitotane inhibits Ca(2+) induced cell shrinkage.

PMID- 24854841
TI  - Dihydroartemisinin accentuates the anti-tumor effects of photodynamic therapy via
      inactivation of NF-kappaB in Eca109 and Ec9706 esophageal cancer cells.
AB  - BACKGROUND: Photodynamic therapy (PDT) is a new treatment for esophageal cancer
      which has been shown to be effective in the elimination of tumor. However, PDT
      could induce the activation of nuclear factor-kappa B (NF-kappaB) in many
      photosensitizers based PDT, which plays a negative role in PDT. In addition, our
      previous results have shown that dihydroartemisinin (DHA), which was the most
      potent one of artemisinin derivatives, has anticancer activity in esophageal
      cancer cells. METHODS: Cell viability was determined by MTT analysis, and
      apoptosis was evaluated by flow cytometry. Nuclear extract was obtained for
      determining NF-kappaB DNA-binding activity, while total protein extract obtained
      for downstream gene expression by western blot. RESULTS: We demonstrated DHA
      enhanced PDT-induced growth inhibition and apoptosis in both human esophageal
      cancer cell lines Eca109 and Ec9706 in vitro. The mechanism was at least
      partially due to DHA deactivated PDT-induced NF-kappaB activation, so as to
      decrease tremendously the expression of its target gene Bcl-2. CONCLUSION: Our
      results demonstrate that DHA augments PDT-induced growth inhibition and apoptosis
      in esophageal cancer cells, and that inactivation of NF-kappaB activity is a
      potential mechanism by which DHA sensitizes esophageal cancer cells to PDT
      induced growth inhibition and apoptosis.

PMID- 24854842
TI  - MicroRNA-127 post-transcriptionally downregulates Sept7 and suppresses cell
      growth in hepatocellular carcinoma cells.
AB  - BACKGROUND/AIMS: Hepatocellular carcinoma is one of the most common cancers
      worldwide. It has been suggested that microRNAs, a class of small regulatory
      RNAs, are associated with tumorigenesis by targeting the mRNAs of hundreds of
      genes that modulate a variety of biological processes, including cellular
      differentiation, apoptosis, metabolism, and proliferation. METHODS/RESULTS: we
      analyzed the expression levels of mir-127 in 33 HCC and non-cancerous tissues
      using qRT-PCR. MiR-127 is downregulated in 69.7% of HCC tissues compared with
      adjacent normal tissues, but its expression level is not correlated with the TNM
      stage, AFP level, or age. In vitro, miR-127 can arrest Huh7 at the G2/M phase and
      inhibit Huh7 cell proliferation. In an in vivo xenograft model, the
      overexpression of miR-127 can inhibit Huh7 cell tumorigenicity. The luciferase
      reporter and western blot results confirm that miR-127 downregulates Sept7
      expression by targeting its 3'UTR. Furthermore, the knockdown of Sept7 has the
      same effect on cell proliferation as the overexpression of miR-127 in Huh7 cells.
      CONCLUSION: miR-127 plays a tumor-suppressor role and can serve as a potential
      diagnostic biomarker for HCC.

PMID- 24854843
TI  - Down-regulation of miR-3928 promoted osteosarcoma growth.
AB  - BACKGROUND: Osteosarcoma is the most common primary bone malignancy in children
      and young adults. Most failures of osteosarcoma treatment were due to resistance
      to chemotherapy. Development of new therapy required elucidation underlying
      molecular mechanism. Many miRNAs have been proved to be involved in the
      pathogenesis of osteosarcoma. METHODS: MiR-3928 expression level was assayed by
      qRT-PCR. MiRNA mimics or ASO were transfected for up-regulation or down
      regulation of miR-3928 expression. Cell proliferation was assayed by formazan
      test. Apoptosis and cell cycle were assayed by FACS. MiR-3928 targeted genes were
      predicated by bioinformatics algorithm (TargetScanHuman). The correlation between
      targeted gene and miR-3928 was analyzed by Pearson's correlation coefficient
      analysis. RESULTS: MiR-3928 was down-regulated in osteosarcoma tissues. Over
      expression of miR-3928 inhibited tumor growth, induced cell apoptosis, increased
      the percent of cells in G1 phrase and decreased the percent of cells in S phrase.
      Down-regulation of miR-3928 promoted cell proliferation. ERBB3, IL-6R and CDK6
      may be the targeted genes of miR-3928. CONCLUSIONS: Down-expression of miR-3928
      in osteosarcoma promoted tumor growth by targeting ERBB3, IL-6R and CDK6. MiR
      3928 may be a potential therapy target worth further investigation.

PMID- 24854844
TI  - MTDH mediates estrogen-independent growth and tamoxifen resistance by down
      regulating PTEN in MCF-7 breast cancer cells.
AB  - BACKGROUND: About 70% of human breast cancers express estrogen receptor alpha
      (ERalpha) and in this kind of breast cancer estrogen plays an important role.
      Estrogen independent growth has been reported to promote resistance to one of the
      selective estrogen receptor modulators (SERMs) tamoxifen which is clinically the
      first line treatment for patients with ERalpha-positive breast cancer. The
      resistance of tamoxifen is a major problem in the clinical management of breast
      cancer. METHODS: We used MCF-7 cells with ectopic expression of MDTH in this
      study. MTT, clone formation and tumor formation in nude mice methods were
      utilized to confirm the role of MTDH in estrogen-independent growth and tamoxifen
      resistance. Flow cytometry, western blot and siRNA were used to study the
      detailed mechanisms. RESULTS: We found that MTDH could mediate estrogen
      independent growth and induce resistance to tamoxifen in ERalpha-positive breast
      cancer cells. MTDH could reduce the expression of PTEN, up-regulate AKT and BCL2
      and inhibit the apoptosis induced by tamoxifen. CONCLUSION: Our study indicated
      that MTDH was a candidate marker to predict the clinical efficacy of tamoxifen
      and targeting MTDH would overcome the resistance to tamoxifen in breast cancer
      cells.

PMID- 24854845
TI  - SREBP-1c gene silencing can decrease lipid deposits in bovine hepatocytes
      cultured in vitro.
AB  - BACKGROUND: Fatty liver is a major metabolic disorder that occurs during early
      lactation in high-producing dairy cows. Sterol regulatory element-binding protein
      1c (SREBP-1c) is an important transcription factor that regulates lipid synthesis
      by regulating the expression of lipid metabolism genes. METHODS: In this study,
      we reduced the expression of SREBP-1c by adenovirus-mediated SREBP-1c with a low
      expression vector (AD-GFP-SREBP-1c) to study the effects of SREBP-1c on lipid
      deposits in bovine hepatocytes. The expression levels and enzyme activities of
      SERBP-1c and its target genes were determined by real-time PCR, western blot, and
      ELISA. RESULTS: These results showed that Ad-GFP-SREBP-1c could inhibit SREBP-1c
      expression. The expression of the lipid synthesis enzyme acetyl-CoA carboxylase
      (ACC) was down-regulated. The expression levels of the lipid oxidation enzymes
      long-chain fatty acyl-COA synthetase (ACSL-1), carnitine palmitoyltransferase I
      (CPT-I), carnitine palmitoyltransferase II (CPT- II), and beta-hydroxyacyl-CoA-DH
      (HADH) were significantly elevated. Furthermore, the expression levels of factors
      involved in the assembly and transport of very low-density lipoproteins (VLDLs),
      such as apolipoprotein B100 (ApoB), apolipoprotein E (ApoE), and microsomal
      triglyceride transfer protein (MTTP) were decreased comparison with the negative
      control and the blank control groups, but the low-density lipoprotein receptor
      (LDLR) was elevated. The concentrations of TG (triglyceride) and VLDL were also
      reduced. CONCLUSION: These data suggest that low SREBP-1c expression can decrease
      lipid synthesis, increase lipid oxidation, and decrease the TG and VLDL content
      in bovine hepatocytes.

PMID- 24854846
TI  - RECQL1 plays an important role in the development of tongue squamous cell
      carcinoma.
AB  - BACKGROUND/AIMS: RECQL1, a member of the human RECQ helicase family, participates
      in DNA repair. Recent reports showed that RECQL1 silencing in cancer cells
      resulted in mitotic catastrophe, which prevented tumor growth in murine models.
      However, its therapeutic potential has never been examined in tongue squamous
      cell carcinoma (SCC). METHODS: To explore the role of RECQL1 in the development
      of tongue SCC, we used RNA interference technology to silence RECQL1 in SCC-9 and
      SCC-15 human tongue SCC cell lines, and to subsequently evaluate its effects both
      in vitro and in vivo. RESULTS: After RECQL1 was silenced in SCC cells by siRNA,
      we observed downregulation of RECQL1 mRNA and protein in cancer cells. RECQL1 is
      one of the predicted miR-203 targets, and we found that miR-203 downregulated the
      expression of RECQL1 at the post-transcriptional level. RECQL1-shRNA or miR-203
      overexpression inhibited SCC-9 cell growth. In addition, there was accumulation
      of cells in the sub-G1 fraction and increased apoptosis 72 h post-transfection.
      In addition, knockdown of RECQL1 led to a strong anticancer effect, as the
      tumorigenicity of SCC-9 cells was inhibited in vivo. Moreover, we found that two
      immunosuppressive factors were also significantly downregulated upon RECQL1
      knockdown or miR-203 overexpression in vitro. CONCLUSION: Collectively, these
      results indicate that RECQL1 plays an important regulatory role in cancer cell
      proliferation and tumor progression.

PMID- 24854847
TI  - Expression of glutamine transporter Slc38a3 (SNAT3) during acidosis is mediated
      by a different mechanism than tissue-specific expression.
AB  - BACKGROUND: Despite homeostatic pH regulation, systemic and cellular pH changes
      take place and strongly influence metabolic processes. Transcription of the
      glutamine transporter SNAT3 (Slc38a3) for instance is highly up-regulated in the
      kidney during metabolic acidosis to provide glutamine for ammonia production.
      METHODS: Slc38a3 promoter activity and messenger RNA stability were measured in
      cultured cells in response to different extracellular pH values. RESULTS: Up
      regulation of SNAT3 mRNA was mediated both by the stabilization of its mRNA and
      by the up-regulation of gene transcription. Stabilisation of the mRNA involved a
      pH-response element, while enhanced transcription made use of a second pH
      sensitive Sp1 binding site in addition to a constitutive Sp1 binding site.
      Transcriptional regulation dominated the early response to acidosis, while mRNA
      stability was more important for chronic adaptation. Tissue-specific expression
      of SNAT3, by contrast, appeared to be controlled by promoter methylation and
      histone modifications. CONCLUSIONS: Regulation of SNAT3 gene expression by
      extracellular pH involves post-transcriptional and transcriptional mechanisms,
      the latter being distinct from the mechanisms that control the tissue-specific
      expression of the gene.

PMID- 24854848
TI  - DSM-5 unspecified feeding and eating disorders in adolescents: what do they look
      like and are they clinically significant?
AB  - OBJECTIVE: The recent DSM-5 categorization of eating disorders introduces a new
      category of eating disorders, Unspecified Feeding and Eating Disorders (UFED),
      where symptoms do not meet criteria for any other diagnostic category, but cause
      clinically significant distress or impairment. The aim of the current study was
      to explore what disorders in UFED might look like in an adolescent population.
      METHOD: We examined a large cohort of adolescent female twins (N = 699) who were
      assessed on three occasions and who did not meet a DSM-5 eating disorder
      diagnosis but who reported threshold levels of either fasting and/or driven
      exercise (N = 33; 4.7%). This group of girls was compared to girls who reported
      no eating disorder over the three waves, and girls who met a diagnosis of either
      anorexia nervosa (AN) or atypical AN. RESULTS: The UFED group was characterized
      as being in the overweight range while striving to lose weight, and placing a
      high degree of importance on weight and shape in their self-evaluation. This
      group was indistinguishable from the two eating disorder groups on measures of
      global eating disorder severity, and demonstrated significantly elevated
      impairment and distress compared to the no eating disorder group commensurate
      with the eating disorder groups. DISCUSSION: Further research of this group is
      necessary to ensure that these individuals are not overlooked, and that treatment
      options are appropriate and available.

PMID- 24854850
TI  - Body mass index is related to microvascular vasomotion, this is partly explained
      by adiponectin.
AB  - OBJECTIVE: obesity-related microvascular dysfunction, including alterations in
      rhythmic changes in vascular diameter, so-called 'vasomotion', may be important
      in the clustering of obesity with other cardiovascular risk factors. Adipokines
      have been suggested to play a role in obesity-related vascular dysfunction.
      Alterations in vasomotion have been found using extreme body mass index (BMI)
      phenotypes. Whether these alterations can be translated to the general population
      is unknown. The aim was to retrospectively investigate relationships between BMI,
      vasomotion and adipokines in a population-based cohort. METHODS: Adiposity,
      vasomotion, adiponectin and leptin were determined in 94 apparently healthy
      participants (age 42 years, 46 men, mean BMI 25.5 +/- 3.8 kg/m(2) ) of the
      Amsterdam Growth and Health Longitudinal Study (AGHLS). Vasomotion was assessed
      via wavelet analysis of skin laser Doppler flowmetry (LDF). RESULTS: BMI was
      associated with the neurogenic domain of the vasomotion spectrum (beta -0.011, P
      = 0.046), adiponectin (beta -0.18, P = 0.028) and leptin (beta 2.22, P < 0.0001).
      Adiponectin was positively associated with the neurogenic domain of vasomotion
      (beta 0.016, P = 0.019). Leptin did not show any significant relationship with
      vasomotion. The association between BMI and the neurogenic domain of the
      vasomotion spectrum was partly explained by adiponectin. CONCLUSIONS: The
      association between adiposity and microvascular vasomotion also applies to the
      normal population and is partly explained by adiponectin.

PMID- 24854851
TI  - Letter to the editor.

PMID- 24854849
TI  - Transposon-mediated targeted and specific knockdown of maternally expressed
      transcripts in the ascidian Ciona intestinalis.
AB  - Maternal mRNAs play crucial roles during early embryogenesis of ascidians, but
      their functions are largely unknown. In this study, we developed a new method to
      specifically knockdown maternal mRNAs in Ciona intestinalis using transposon
      mediated transgenesis. We found that GFP expression is epigenetically silenced in
      Ciona intestinalis oocytes and eggs, and this epigenetic silencing of GFP was
      used to develop the knockdown method. When the 5' upstream promoter and 5'
      untranslated region (UTR) of a maternal gene are used to drive GFP in eggs, the
      maternal gene is specifically knocked down together with GFP. The 5' UTR of the
      maternal gene is the major element that determines the target gene silencing.
      Zygotic transcription of the target gene is unaffected, suggesting that the
      observed phenotypes specifically reflect the maternal function of the gene. This
      new method can provide breakthroughs in studying the functions of maternal mRNAs.

PMID- 24854852
TI  - Angiographic features of transgenic mice with increased expression of human
      serine protease HTRA1 in retinal pigment epithelium.
AB  - PURPOSE: Polypoidal choroidal vasculopathy (PCV) is characterized by a branching
      vascular network (BVN) of choroid that terminates in polypoidal dilations. We
      have previously reported the generation of the first PCV model by transgenically
      expressing human HTRA1 (hHTRA1(+)), a multifunctional serine protease, in mouse
      RPE. The purpose of this study was to perform a comprehensive examination of the
      PCV phenotypes (e.g., lesion type and distribution) of hHTRA1(+) mice by a
      variety of in vivo imaging techniques. METHODS: We generated improved hHTRA1(+)
      mice with a more consistent phenotype. Transgenic mice were examined by
      indocyanine green angiography (ICGA), fluorescein angiography, funduscopy, and
      spectral-domain optical coherence tomography. In particular, we performed ICGA by
      tail vein injection of ICG to obtain high-quality ICGA comparable to human
      studies in terms of the three phases (early, middle, and late) of angiography.
      RESULTS: The polyps can be detected in the early "fill-in" phase of ICGA, and
      most lesions become visible in the middle phase and are more distinct in the late
      phase with the fading of surrounding vessels. In addition to the two key features
      of PCV (polypoidal dilations and BVNs), hHTRA1(+) mice exhibit other features of
      PCV (i.e., late geographic hyperfluorescence, pigment epithelial detachment, and
      hyperfluorescent plaque). Polypoidal lesions appear as reddish orange nodules on
      funduscopy. CONCLUSIONS: Transgenic hHTRA1(+) mice exhibit a rich spectrum of
      "clinical" features that closely mimic human PCV. This animal model will serve as
      an invaluable tool for future mechanistic and translational studies of PCV and
      other forms of choroidal vasculopathies.

PMID- 24854855
TI  - Extended association study of PLEKHA7 and COL11A1 with primary angle closure
      glaucoma in a Han Chinese population.
AB  - PURPOSE: To investigate the association of PLEKHA7 and COL11A1 with primary angle
      closure glaucoma, as well as acute and chronic subphenotype, in a Han Chinese
      population. METHODS: A total of 984 cases, including 606 primary angle closure
      glaucoma (PACG) and 378 primary angle closure (PAC), and 922 normal controls were
      recruited. Twelve single nucleotide polymorphisms (SNPs) (rs1676486, rs3753841,
      rs12138977, rs2126642, rs2622848, rs216489, rs1027617, rs366590, rs11024060,
      rs6486330, rs11024097, and rs11024102) in the PLEKHA7 gene and COL11A12 gene were
      genotyped. Distributions of allele frequencies were compared between cases and
      controls as well as in patient subgroups with or without acute attacks. RESULTS:
      Four of the 12 SNPs, including rs1676486 (P = 0.0060) and rs12138977 (P = 0.028)
      in COL11A1, as well as rs216489 (P = 0.0074) and rs11024102 (P = 0.038) in
      PLEKHA7, were found to have a statistically significant association with
      PAC/PACG. In the subgroup analysis, 6 out of 12 SNPs (rs1676486, rs3753841,
      rs12138977, rs216489, rs11024060, and rs11024102) showed statistically
      significant differences between acute PAC/PACG cases and controls. However, none
      of them showed statistically significant differences between chronic PAC/PACG
      cases and controls. CONCLUSIONS: Our study suggests that rs1676486 and rs12138977
      in COL11A1 as well as rs216489 and rs11024102 in PLEKHA7 are associated with an
      increased risk of PAC/PACG in the Han Chinese population, supporting prior
      reports of the association of COL11A1 and PLEKH7 with angle closure glaucoma.
      Both COL11A1 and PLEKHA7 were shown to confer significant risk for acute
      PAC/PACG. Further work is necessary to confirm the importance of COL11A1 and
      PLEKHA7 in the pathogenesis of glaucoma.

PMID- 24854853
TI  - Strain difference in photoreceptor cell death after retinal detachment in mice.
AB  - PURPOSE: To evaluate the potential for mouse genetic background to effect
      photoreceptor cell death in response to experimental retinal detachment (RD).
      METHODS: Retinal detachment was induced in three inbred mouse strains (C57BL/6,
      BALB/c, and B6129SF2) by subretinal injection of sodium hyaluronate. A time
      course of photoreceptor cell death was assessed by TUNEL assay. Total
      photoreceptor cell death was analyzed through comparing the outer nuclear layer
      (ONL)/inner nuclear layer (INL) ratio 7 days post RD. Western blot analysis or
      quantitative real-time PCR (qPCR) were performed to assess cell death signaling,
      expression of endogenous neurotrophin, and levels of apoptosis inhibitors 24
      hours after RD. Inflammatory cytokine secretion and inflammatory cell
      infiltration were quantified by ELISA and immunostaining, respectively. RESULTS:
      The peak of photoreceptor cell death after RD was at 24 hours in all strains.
      Photoreceptor cell death as well as monocyte chemoattractant protein 1 and
      interleukin 6 secretion at 24 hours after RD was the highest in BALB/c, followed
      in order of magnitude by C57BL/6 and B6129SF2. Conversely, nerve growth factor
      expression and ONL/INL ratio were the lowest in BALB/c. Apoptosis signaling was
      higher in C57BL/6, whereas necroptosis signaling was higher in C57BL/6 and
      BALB/c. Autophagic signaling was higher in BALB/c. X-linked inhibitor of
      apoptosis (XIAP) and survivin protein levels were lower in C57BL/6 and BALB/c,
      respectively. Macrophage/microglia infiltration was higher in C57BL/6 and BALB/c
      at 24 hours after RD. CONCLUSIONS: Photoreceptor cell death after RD was
      significantly different among the three strains, suggesting the presence of
      genetic factors that affect photoreceptor cell death after RD.

PMID- 24854854
TI  - Angiotensin-converting enzyme 2 (ACE2) activator diminazene aceturate ameliorates
      endotoxin-induced uveitis in mice.
AB  - PURPOSE: Uveitis is a common cause of vision loss. The renin angiotensin system
      (RAS), which plays a vital role in cardiovascular system, is a potent mediator of
      inflammation and has been implicated in the pathogenesis of uveitis. A newly
      identified axis of RAS, ACE2/Ang-(1-7)/Mas, has emerged as a novel target because
      it counteracts the deleterious effect of angiotensin II. The purpose of this
      study was to investigate the effect of endogenous ACE2 activation in preventing
      endotoxin-induced uveitis (EIU) in mice. METHODS: ACE2 activator diminazene
      aceturate (DIZE) was administered both systemically and locally. For systemic
      administration, female BALB/c mice received intraperitoneal injection of DIZE (60
      mg/kg body weight [BW]) for 2 days prior to lipopolysaccharide (LPS) intravitreal
      injection (125 ng) to induce uveitis. For local study, DIZE was given at 0.5,
      0.1, and 0 mg/mL as eyedrops six times per day for 2 days before LPS injection.
      The anterior segment of the mice was examined at 12, 24, 48, and 72 hours after
      LPS injection, and clinical scores were determined at the same time. Morphology
      and infiltrating inflammatory cells were evaluated after 24 hours. The mRNA
      levels of inflammatory cytokines were analyzed by real-time RT-PCR. ACE2 activity
      was determined using a self-quenching fluorescent substrate. RESULTS: At 24
      hours, the clinical score of mice treated with DIZE systemically was
      significantly lower (mean, ~1.75) than the saline vehicle group (mean, ~4) (P <
      0.001). Histological examination showed 63.4% reduction of infiltrating
      inflammatory cells in the anterior segment and 57.4% reduction in the posterior
      segment of DIZE-treated eyes. The number of CD45(+) inflammatory cells in the
      vitreous of the DIZE-treated group was decreased (43.3%) compared to the vehicle
      group (P < 0.01). The mRNA levels of inflammatory cytokines were significantly
      reduced in the DIZE-treated group (P < 0.01, P < 0.001). The number of
      infiltrating inflammatory cells was also significantly reduced in eyes that
      received topical administration of DIZE: 73.8% reduction in the 0.5 mg/mL group
      and 51.7% reduction in the 0.1mg/mL group compared to the control group. DIZE
      treatment resulted in significantly increased ACE2 activity in the retina (P <
      0.001). CONCLUSIONS: Endogenous ACE2 activation by DIZE has a preventive effect
      on LPS-induced ocular inflammation in the EIU mouse model. These results support
      the notions that RAS plays a role in modulating ocular immune response and that
      enhancing ACE2 provides a novel therapeutic strategy for uveitis.

PMID- 24854856
TI  - Monitoring retinal morphologic and functional changes in mice following optic
      nerve crush.
AB  - PURPOSE: We characterized the morphologic and functional changes in optic nerve
      crushed mice and evaluated electroretinogram (ERG) responses as tools to monitor
      retinal ganglion cell (RGC) dysfunction. METHODS: We performed optic nerve crush
      (ONC) unilaterally in adult BALB/cJ mice. The neuronal loss in the RGC layer
      (GCL) and superior colliculus (SC) was determined by Nissl staining. Retinal
      thickness was assessed by spectral-domain optical coherence tomography (SD-OCT)
      imaging. Retinal function was determined by pattern ERG and full-field flash ERG.
      Responses of pattern ERG, positive scotopic threshold response (pSTR), scotopic
      oscillatory potentials (OPs), and photopic negative response (PhNR) were
      analyzed. RESULTS: The ONC induced progressive neuronal loss in GCL and
      contralateral SC starting from 7 and 28 days following ONC, respectively. A
      linear correlation was observed between combined thickness of nerve fiber layer
      (NFL), GCL, and inner plexiform layer (IPL) imaged by SD-OCT and cell numbers in
      GCL. Only half of the normal BALB/cJ mice exhibited pattern ERG response, which
      was smaller and later compared to C57BL/6J mice. The ONC reduced pattern ERG and
      pSTR, but the reduction of pattern ERG was earlier than pSTR, preceding the
      anatomical cell loss in the GCL. The PhNR and scotopic OPs were not affected by
      ONC. CONCLUSIONS: The SD-OCT and ERG can be used to monitor noninvasively retinal
      morphologic and functional changes induced by ONC. Pattern ERG and pSTR are able
      to detect early RGC dysfunction, but pattern ERG exhibits higher sensitivity. Our
      results support the use of these tools in studies using the mouse ONC model.

PMID- 24854858
TI  - Essential role of the chaperonin CCT in rod outer segment biogenesis.
AB  - PURPOSE: While some evidence suggests an essential role for the chaperonin
      containing t-complex protein 1 (CCT) in ciliogenesis, this function remains
      poorly understood mechanistically. We used transgenic mice, previously generated
      in our lab, and characterized by a genetically-induced suppression of CCT in rod
      photoreceptors as well as a malformation of the rod sensory cilia, the outer
      segments, to gain new insights into this underlying molecular mechanism. METHODS:
      The CCT activity in rod photoreceptors of mice was suppressed by overexpressing
      the chaperonin inhibitor, phosducin-like protein short, and the ensuing changes
      of cellular morphology were analyzed by light and electron microscopy. Protein
      expression levels were studied by fluorescent microscopy and Western blotting.
      RESULTS: Suppressing the chaperonin made the photoreceptors incompetent to build
      their outer segments. Specifically, the CCT-deficient rods appeared unable to
      expand the outer segment plasma membrane, and accommodate growth of this
      compartment. Seeking the molecular mechanisms underlying such a shortcoming, we
      found that the affected rods could not express normal levels of Bardet-Biedl
      Syndrome (BBS) proteins 2, 5, and 7 and, owing to that deficiency, were unable to
      assemble the BBSome, a multisubunit complex responsible for ciliary trafficking.
      A similar effect in response to the chaperonin suppression was also observed in
      cultured ciliated cells. CONCLUSIONS: Our data provide new evidence indicating
      the essential role of the chaperonin CCT in the biogenesis of vertebrate
      photoreceptor sensory cilia, and suggest that it may be due to the direct
      participation of the chaperonin in the posttranslational processing of selected
      BBS proteins and assembly of the BBSome.

PMID- 24854857
TI  - Associations between abnormal rod-mediated dark adaptation and health and
      functioning in older adults with normal macular health.
AB  - PURPOSE: Delayed rod-mediated dark adaptation (DA) is characteristic of early age
      related macular degeneration (AMD) and also can be observed in some older adults
      in normal macular health. We examine cross-sectional associations between rod
      mediated DA and risk factors for AMD in older adults in normal macular health.
      METHODS: The sample consisted of adults aged >=60 years old in normal macular
      health per grading of fundus photos using an established disease classification
      system. Rod-mediated DA was measured psychophysically following a photobleach
      using a computer-automated dark adaptometer with targets centered at 5 degrees 
      on the inferior vertical meridian. The speed of DA was characterized by the rod
      intercept value, with abnormal DA defined as rod-intercept >= 12.3 minutes. We
      assessed several health and functional characteristics that the literature has
      suggested increase AMD risk (e.g., smoking, alcohol use, inflammatory markers,
      apolipoproteins, low luminance visual acuity, chronic medical conditions, body
      mass, family history). RESULTS: Among 381 participants (mean age, 68.5 years; SD,
      5.5), 78% had normal and 22% had abnormal DA, with the prevalence of abnormal DA
      increasing with age. After age-adjustment, abnormal DA was associated with
      increased odds of elevated C-reactive protein (CRP), heavy use of or abstention
      from alcohol, high blood pressure, and drop in visual acuity under mesopic
      conditions. CONCLUSIONS: Despite having normal macular health according to
      accepted definitions of AMD presence, approximately one-quarter of older adults
      recruited from primary eye care clinics had abnormal DA, which was associated
      with known risk factors for AMD, including elevated CRP.

PMID- 24854861
TI  - A novel feeder-free culture system for expansion of mouse spermatogonial stem
      cells.
AB  - Spermatogonial stem cells (SSCs, also called germline stem cells) are self
      renewing unipotent stem cells that produce differentiating germ cells in the
      testis. SSCs can be isolated from the testis and cultured in vitro for long-term
      periods in the presence of feeder cells (often mouse embryonic fibroblasts).
      However, the maintenance of SSC feeder culture systems is tedious because
      preparation of feeder cells is needed at each subculture. In this study, we
      developed a Matrigel-based feeder-free culture system for long-term propagation
      of SSCs. Although several in vitro SSC culture systems without feeder cells have
      been previously described, our Matrigel-based feeder-free culture system is time-
      and cost- effective, and preserves self-renewability of SSCs. In addition, the
      growth rate of SSCs cultured using our newly developed system is equivalent to
      that in feeder cultures. We confirmed that the feeder-free cultured SSCs
      expressed germ cell markers both at the mRNA and protein levels. Furthermore, the
      functionality of feeder-free cultured SSCs was confirmed by their transplantation
      into germ cell-depleted mice. These results suggest that our newly developed
      feeder-free culture system provides a simple approach to maintaining SSCs in
      vitro and studying the basic biology of SSCs, including determination of their
      fate. 

PMID- 24854859
TI  - Vimentin knockdown decreases corneal opacity.
AB  - PURPOSE: Wound induced corneal fibrosis can lead to permanent visual impairment.
      Keratocyte activation and differentiation play a key role in fibrosis, and
      vimentin, a major structural type III intermediate filament, is a required
      component of this process. The purpose of our study was to develop a nonviral
      therapeutic strategy for treating corneal fibrosis in which we targeted the
      knockdown of vimentin. METHODS: To determine the duration of plasmid expression
      in corneal keratocytes, we injected a naked plasmid expressing green fluorescent
      protein (GFP; pCMV-GFP) into an unwounded mouse corneal stroma. We then injected
      pCMV-GFP or plasmids expressing small hairpin RNA in the corneal wound injury
      model (full-thickness corneal incision) to evaluate opacification. RESULTS: GFP
      expression peaked between days 1 and 3 and had prominent expression for 15 days.
      In the corneal wound injury model, we found that the GFP-positive cells
      demonstrated extensive dendritic-like processes that extended to adjacent cells,
      whereas the vimentin knockdown model showed significantly reduced corneal
      opacity. CONCLUSIONS: These findings suggest that a nonviral gene therapeutic
      approach has potential for treating corneal fibrosis and ultimately reducing
      scarring.

PMID- 24854862
TI  - Characterization of antiproliferative activity constituents from Artocarpus
      heterophyllus.
AB  - Artocarpus heterophyllus is an evergreen fruit tree cultivated in many tropical
      regions. Previous studies have shown that some of its compositions exhibited
      potential tyrosinase inhibition activities. This study indentified 8 new phenolic
      compounds, artoheterophyllins E-J (1-6), 4-geranyl-2',3,4',5-tetrahydroxy-cis
      stilbene (7), and 5-methoxymorican M (8) and 2 new natural compounds (9 and 10),
      2,3-dihydro-5,7-dihydroxy-2-(2-hydroxy-4-methoxyphenyl)-4H-benzopyran-4-one and 6
      [(1S,2S)-1,2-dihydroxy-3-methylbutyl]-2-(2,4-dihydroxyphenyl)-5-hydroxy-7-methoxy
      3-(3-methyl-2-buten-1-yl)-4H-1-benzopyran-4-one, together with 23 known compounds
      (11-33), from the ethanol extract of the wood of A. heterophyllus. The structures
      of the eight new compounds (1-8) and two new natural compounds were established
      by extensive 1D- and 2D-NMR experiments. The anticancer effects of the isolated
      compounds were examined in MCF-7, H460, and SMMC-7721 human cancer cell lines by
      MTT assay. Compounds 5, 11, 12, and 30 significantly reduced the cell viabilities
      of these cell lines. Especially, compounds 11 and 30 resulted in more potent
      cytotoxicity than the positive control, 5-fluorouracil (5-Fu), in SMMC-7721 cell
      line, with IC50 values of 15.85 and 12.06 MUM, whereas compound 30 exhibited more
      potent cytotoxicity than 5-Fu in NCI-H460 cell line, with an IC50 value of 5.19
      MUM. In addition, this study suggests that compounds 11 and 30 from the wood of
      A. heterophyllus have anticancer potential via MAPK pathways. 

PMID- 24854860
TI  - A tale of two models: mouse and zebrafish as complementary models for lymphatic
      studies.
AB  - Lymphatic vessels provide essential roles in maintaining fluid homeostasis and
      lipid absorption. Dysfunctions of the lymphatic vessels lead to debilitating
      pathological conditions, collectively known as lymphedema. In addition, lymphatic
      vessels are a critical moderator for the onset and progression of diverse human
      diseases including metastatic cancer and obesity. Despite their clinical
      importance, there is no currently effective pharmacological therapy to regulate
      functions of lymphatic vessels. Recent efforts to manipulate the Vascular
      Endothelial Growth Factor-C (VEGFC) pathway, which is arguably the most important
      signaling pathway regulating lymphatic endothelial cells, to alleviate lymphedema
      yielded largely mixed results, necessitating identification of new targetable
      signaling pathways for therapeutic intervention for lymphedema. Zebrafish, a
      relatively new model system to investigate lymphatic biology, appears to be an
      ideal model to identify novel therapeutic targets for lymphatic biology. In this
      review, we will provide an overview of our current understanding of the lymphatic
      vessels in vertebrates, and discuss zebrafish as a promising in vivo model to
      study lymphatic vessels. 

PMID- 24854863
TI  - Age- and gene-dosage-dependent cre-induced abnormalities in the retinal pigment
      epithelium.
AB  - To conditionally inactivate genes in the retinal pigment epithelium (RPE)
      transgenic mouse strains have been developed, in which Cre recombinase (Cre)
      expression is driven by an RPE-specific gene promoter. The RPE is a quiescent
      epithelium, and continuous expression of Cre could affect its function. Here, we
      tested the hypothesis that continuous postnatal Cre expression in the RPE may
      lead to cellular abnormalities, which may depend on both age and Cre gene dosage.
      We therefore examined the eyes of homozygous and heterozygous VMD2-Cre mice at
      various ages. In VMD2-Cre heterozygous mice variable progressive age-dependent
      RPE abnormalities were noticed, including attenuation of phalloidin and
      cytoplasmic active beta-catenin staining, reduced cell size, and loss of the
      typical honeycomb pattern of RPE morphology in those RPE cells that stained for
      Cre. These morphological RPE abnormalities were not noticed in Cre-negative RPE
      cells in VMD2-Cre or age-matched control mice. In addition, an abnormal number
      and morphology of cell nuclei were noticed in a subset of Cre-expressing RPE
      cells in aged heterozygous VMD2-Cre mice, whereas more severe nuclear
      abnormalities were observed already in young homozygous VMD2-Cre mice. Thus,
      continuous postnatal expression of Cre causes abnormalities in the RPE in an age-
      and Cre gene dosage-dependent manner, which needs to be considered in the
      interpretation of gene targeting studies in the RPE. 

PMID- 24854865
TI  - Overexpression of juxtaposed with another zinc finger gene 1 reduces
      proinflammatory cytokine release via inhibition of stress-activated protein
      kinases and nuclear factor-kappaB.
AB  - As an inhibitor of the nuclear receptor subfamily 2, group C, member 2 signaling
      pathway, juxtaposed with another zinc finger gene 1 (JAZF1) has been shown to be
      involved in gluconeogenesis, lipid metabolism, and insulin sensitivity. However,
      its role in hepatic lipogenesis and chronic low-grade inflammation leading to
      nonalcoholic fatty liver disease remains unknown. The aim of this study was to
      examine whether JAZF1 overexpression in vivo or in vitro can protect against
      palmitic acid (PA)-induced and high-fat diet (HFD)-induced systemic inflammatory
      responses, and the potential mechanism of this process. JAZF1 overexpression
      vector was transfected into PA-treated IAR-20 hepatocytes. The mRNA expression
      levels of proinflammatory cytokines were measured by real-time quantitative PCR,
      and stress-activated protein kinase activities were measured by immunoblotting.
      For in vivo studies, JAZF1 transgenic mice were fed an HFD for 12 weeks. Liver
      tissue was obtained for histological examination, real-time RT-PCR, and western
      blot analysis. PA significantly increased the expression levels of tumor necrosis
      factor-alpha, monocyte chemotactic protein-1 and interleukin-8 mRNA in IAR-20
      hepatocytes in a dose-dependent and time-dependent manner. Treatment with JAZF1
      or stress-activated protein kinase inhibitors inhibited PA-induced tumor necrosis
      factor-alpha, monocyte chemotactic protein-1 and interleukin-8 expression in
      these cells. In JAZF1-treated cells, the decreased expression of proinflammatory
      cytokines was accompanied by decreased p38 mitogen-activated protein kinase and c
      Jun N-terminal kinase phosphorylation and increased nuclear factor-kappaB
      inhibitor-alpha protein levels, similarly to the role of signaling inhibitors. In
      vivo, HFD-induced expression of proinflammatory cytokines was markedly attenuated
      in JAZF1-Tg mice as compared with controls. This attenuation was accompanied by
      decreased activation of c-Jun N-terminal kinase, p38 mitogen-activated protein
      kinase, and nuclear factor-kappaB. These data provide evidence for the important
      role of JAZF1 in preventing lipogenesis and systemic inflammation-related
      disease.

PMID- 24854866
TI  - Role of ganglion cell complex in visual recovery following surgical internal
      limiting membrane peeling.
AB  - PURPOSE: To investigate the Ganglion Cell Complex (GCC) thickness change and
      visual recovery correlation after surgery for an idiopathic epiretinal membrane
      (ERM). METHODS: In this prospective, observational, case control study 30 eyes
      underwent vitrectomy for idiopathic ERM. We analysed best-corrected visual acuity
      (BCVA), mean macular thickness and mean GCC thickness one day before surgery,
      seven days and six months after surgery. Internal segment/outer segment junction,
      external limiting membrane, cone outer segment tips defects and intraretinalfluid
      were also investigated throughout the follow-up. RESULTS: Baseline GCC thickness
      was higher in patients with ERM (130 +/- 13 MUm) compared with healthy eyes (94
      +/- 5 MUm; p < 0.0001). GCC thickness decreased after surgery to 89 +/- 11 MUm (p
      < 0.0001), reaching a value similar to controls (p = 0.12). Preoperative macular
      thickness was 318 +/- 32 MUm and decreased to 281 +/- 18 MUm (p < 0.0001),
      remaining significantly higher than controls (260 +/- 8 MUm; p < 0.0001). The GCC
      proportion of the whole macular thickness was also reduced six months after
      surgery (p < 0.0001). Post-operative BCVA gain showed direct correlation with GCC
      reduction (R = 0.67, p < 0.0001), but did not correlate with the mean macular
      thickness reduction (R < 0.01, p = 0.97). CONCLUSIONS: Ganglion cell complex
      thickness is higher in eyes with idiopathic ERM, and after surgery turns back to
      similar values of healthy eyes. Post-operative GCC reduction is proportionally
      higher than thinning of the whole retina, and this reduction is correlated with
      visual restoration.

PMID- 24854864
TI  - Acute lipotoxicity regulates severity of biliary acute pancreatitis without
      affecting its initiation.
AB  - Obese patients have worse outcomes during acute pancreatitis (AP). Previous
      animal models of AP have found worse outcomes in obese rodents who may have a
      baseline proinflammatory state. Our aim was to study the role of acute lipolytic
      generation of fatty acids on local severity and systemic complications of AP.
      Human postpancreatitis necrotic collections were analyzed for unsaturated fatty
      acids (UFAs) and saturated fatty acids. A model of biliary AP was designed to
      replicate the human variables by intraductal injection of the triglyceride
      glyceryl trilinoleate alone or with the chemically distinct lipase inhibitors
      orlistat or cetilistat. Parameters of AP etiology and outcomes of local and
      systemic severity were measured. Patients with postpancreatitis necrotic
      collections were obese, and 13 of 15 had biliary AP. Postpancreatitis necrotic
      collections were enriched in UFAs. Intraductal glyceryl trilinoleate with or
      without the lipase inhibitors resulted in oil red O-positive areas, resembling
      intrapancreatic fat. Both lipase inhibitors reduced the glyceryl trilinoleate
      induced increase in serum lipase, UFAs, pancreatic necrosis, serum inflammatory
      markers, systemic injury, and mortality but not serum alanine aminotransferase,
      bilirubin, or amylase. We conclude that UFAs are enriched in human necrotic
      collections and acute UFA generation via lipolysis worsens pancreatic necrosis,
      systemic inflammation, and injury associated with severe AP. Inhibition of
      lipolysis reduces UFA generation and improves these outcomes of AP without
      interfering with its induction. 

PMID- 24854867
TI  - Cloning of cDNAs for H1F0, TOP1, CLTA and CDK1 and the effects of
      cryopreservation on the expression of their mRNA transcripts in yak (Bos
      grunniens) oocytes.
AB  - INTRODUCTION: We cloned and sequenced four pivotal cDNAs involved in DNA
      structural maintenance (H1F0 and TOP1) and the cell cycle (CLTA and CDK1) from
      yak oocytes. In addition, we studied the consequences of freezing-thawing (F/T)
      processes on the expression of their mRNA transcripts in yak immature and in
      vitro matured (MII) oocytes. MATERIAL AND METHODS: H1F0, TOP1, CLTA and CDK1
      cDNAs were cloned from yak oocytes by reverse transcriptase-polymerase chain
      reaction (RT-PCR) strategy. The expression of their mRNA transcript analyses were
      performed upon fresh and frozen-thawed immature germinal vesicle (GV) and MII yak
      oocytes following normalization of transcripts with GAPDH by real-time PCR.
      RESULTS: The yak H1F0, TOP1, CLTA and CDK1 cDNA sequences were found to consist
      of CDK1 585, 2539, 740, and 894 bp, respectively. Their coding regions encoded
      195, 768, 244, and 298 amino acids, respectively. The homology with that of
      cattle was very high (95.2%, 98.8%, 93.6%, and 89.5%, respectively nucleotide
      sequence level, and 94.3%, 98.2%, 87.7%, and 90.9%, respectively at the deduced
      amino acid level). The overall mRNA expression levels of these four transcripts
      were reduced by F/T process, albeit at different levels. TOP1 in GV-oocytes, and
      H1F0 and CDK1 in MII-oocytes of the yak were significantly down-regulated
      (P<0.05). CONCLUSIONS: This is the first isolation and characterization of H1F0,
      TOP1, CLTA, and CDK1 cDNAs from yak oocytes. The lower fertility and
      developmental ability of yak oocytes following fertilization after
      cryopreservation may be explained by the alterations to their gene expression
      profiles.

PMID- 24854868
TI  - Different concentrations of cysteamine and ergothioneine improve microscopic and
      oxidative parameters in ram semen frozen with a soybean lecithin extender.
AB  - The aim of this study was to evaluate the effects of ergothioneine and cysteamine
      as antioxidant supplements in a soybean lecithin extender for freezing ram semen.
      Twenty-four ejaculates were collected from four rams and diluted with extenders
      (1.5% soybean lecithin, 7% glycerol) containing no supplements (control) and
      cysteamine or ergothioneine (2, 4, 6 or 8mM). Motility by CASA, viability, plasma
      membrane functionality (HOS test), total abnormality, lipid peroxidation,
      glutathione peroxidase (GPx) activity and capacitation status (CTC staining) were
      assessed after thawing. Using 6mM of either antioxidant improved total motility.
      Cysteamine at 6mM and ergothioneine at 4 and 6mM improved viability and reduced
      lipid peroxidation (malondialdehyde concentration). Both antioxidants improved
      membrane functionality significantly, except at 8mM. Progressive motility,
      kinematic parameters, GPx activity, capacitation status and sperm abnormalities
      were not influenced by the antioxidant supplements. In conclusion, cysteamine at
      6mM and ergothioneine at 4 or 6mM seem to improve the post-thawing quality of ram
      semen cryopreserved in a soybean lecithin extender. 

PMID- 24854869
TI  - The effect of intrathecal administration TRPA1 antagonists in a rat model of
      neuropathic pain.
AB  - BACKGROUND: The fact that transient receptor potential ankyrin 1 (TRPA1) on the
      peripheral terminals could attenuate hyperalgesia is widely accepted, but the
      effect of spinal TRPA1 in the modulation of hyperalgesia has not been fully
      demonstrated. In the present study, we investigated the effect of intrathecal
      (i.t.) administration TRPA1 antagonists on chronic pain and expression of TRPA1
      and phosphorylation N-methyl-D-aspartate receptor 2B subunit (p-NR2B) in the
      spinal cord with chronic compression of the dorsal root ganglia (CCD) in rats.
      METHODS: The study was conducted in 2 parts. Part 1: Sixteen rats were divided
      into 2 groups (n = 8 each): a sham group and CCD group. Paw withdrawal mechanical
      thresholds (PWMT) were measured at baseline and 1, 3, 7, 10, 14, and 21 days
      after CCD. Sixteen other rats were used to evaluate expression of TRPA1 and p
      NR2B in spinal cord on the seventh and 14th days after CCD; Western blotting was
      used to evaluate expression levels (n = 4 each). Part 2: 40 rats were divided
      into 5 groups (n = 8 each): CCD group, CCD + Vehicle group, CCD + HC-030031(10
      MUg, i.t.) group, CCD + HC-030031(25 MUg, i.t.) group, and CCD + HC-030031(50
      MUg, i.t.) group. PWMTs were measured at baseline and 0.5, 1, 2, 4, and 6 hours
      after i.t. HC-030031 on the third, seventh, 10th, and 14th days after CCD.
      Another 48 rats were used to evaluate expression of TRPA1 and p-NR2B in spinal
      cord 2 hours after injection on the seventh and 14th days after CCD in groups
      CCD, CCD + Vehicle, and CCD+ HC-030031(50 MUg, i.t.) using Western blotting (n =
      4 each). RESULTS: Compared with the sham group, PWMT was significantly decreased,
      and protein expression of TRPA1 and p-NR2B were upregulated, in spinal cord on
      the seventh and 14th days after CCD operation. TRPA1 antagonists (HC-030031, 50
      MUg, i.t.) increased the PWMT after CCD and downregulated the protein level of
      TRPA1 and p-NR2B in spinal cord at 2 hours after the injection on the seventh and
      14th days after CCD. CONCLUSIONS: These data demonstrated that the i.t.
      administration of TRPA1 antagonists could attenuate neuropathic pain in CCD rats,
      and this effect could be partially reduced by p-NR2B receptor expression in
      spinal cord.

PMID- 24854870
TI  - The effect and duration of prophylactic platelet transfusions before insertion of
      a central venous catheter in patients with bone marrow failure evaluated with
      point-of-care methods and flow cytometry.
AB  - BACKGROUND: Patients with bone marrow failure and severe thrombocytopenia are
      frequently given prophylactic platelet transfusion before interventions. The
      clinical effects of such transfusions, however, are poorly defined. We performed
      a prospective observational study on patients with bone marrow failure scheduled
      for prophylactic platelet transfusion before the insertion of a central venous
      catheter. The objectives were to evaluate the effect and duration of prophylactic
      platelet transfusions on central venous catheter insertion in thrombocytopenic
      patients with bone marrow failure. METHODS: Thirty-nine adult patients with bone
      marrow failure and platelet counts below 50 * 10/L were consecutively enrolled
      before prophylactic platelet transfusion for subclavian central venous catheter
      insertion. Blood samples were drawn from the patients before platelet
      transfusion, 1 hour, and 4 hours after completion of the transfusion. The
      coagulation profile was assessed by conventional hematological tests,
      thromboelastometry (ROTEM) assays (EXTEM and FIBTEM), multiple electrode
      aggregometry (Multiplate) assays including adenosine diphosphate, collagen, and
      thrombin receptor agonist peptide, and by flow cytometry for the platelet
      expression of P-selectin (CD62P) and activated glycoprotein IIb-IIIa (PAC-1).
      Bleeding complications were classified with a 5-grade scale, according to the
      Common Terminology Criteria for Adverse Events. RESULTS: Seventeen women and 22
      men were included in the study. Platelet count was increased from 24 * 10/L (18
      32) before to 42 * 10/L (31-50) 1 hour after transfusion (P < 0.0001) and was not
      significantly different 4 hours after transfusion (40 * 10/L (29-50), P = 0.047).
      Maximal clot firmness EXTEM was increased from 38 mm (32-45) before to 46 mm (41
      52) 1 hour after transfusion (P < 0.0001) and did not change 4 hours after
      transfusion. Clotting time EXTEM was decreased from 58.5 seconds (50-78)
      beforehand to 53 seconds (45-61) 1 hour after transfusion (P = 0.0006) and was
      not significantly different 4 hours after transfusion (57 seconds (52-70, P =
      0.025). FIBTEM results were all unchanged after transfusion. All Multiplate
      analyses were significantly increased after 1 hour and were not diminished 4
      hours after transfusion. Four grade 1 bleeding episodes occurred, but no grade 2
      to 5 bleeding could be detected. Flow cytometry analyses showed mixed results
      with no overall trend. CONCLUSIONS: Prophylactic platelet transfusions in
      thrombocytopenic patients with bone marrow failure improve hemostatic parameters
      on ROTEM and Multiplate by increasing the number of platelets, and not through
      enhancement of platelet function. Improved clotting parameters on ROTEM and
      platelet aggregation on Multiplate appear to persist between 1 and 4 hours after
      transfusion.

PMID- 24854871
TI  - A prospective observational study of ethnic and racial differences in neuraxial
      labor analgesia request and pain relief.
AB  - BACKGROUND: As ethnic and racial diversity increases, it is important that
      anesthesia providers understand the expectations and concerns of this changing
      population regarding labor analgesia. Our objective was to evaluate ethnic/racial
      differences in labor analgesia characteristics with regard to the timing of
      request for neuraxial analgesia. METHODS: Three hundred ninety-seven parturients
      were enrolled in this prospective observational cohort study. Term laboring
      parturients who planned vaginal delivery and requested neuraxial labor analgesia
      were eligible for inclusion. Data collected included cervical dilation at the
      time of neuraxial analgesia request, self-identified ethnicity/race, parity,
      education, insurance status, pain score before and after the initiation of
      neuraxial analgesia, and mode of delivery. The primary outcome was cervical
      dilation at the time of neuraxial analgesia request. Ethnicity/race
      classification was determined by asking the patient, "How would you define your
      ethnicity?" Patients were categorized into the ethnic/racial groups of non
      Hispanic White, African American, Hispanic, or other. Univariate associations
      between cervical dilation and categorical variables were examined. Multivariate
      analysis was performed for the primary outcome of cervical dilation at the time
      of initiation of neuraxial analgesia. RESULTS: At the time of neuraxial analgesia
      placement, the mean difference in cervical dilation of Hispanic parturients was
      0.8 cm compared to non-Hispanic Whites (95% confidence interval [CI], 0.1-1.4; P
      = 0.047). After controlling for education, reason for placement, labor
      augmentation, and mode of delivery in a multivariate model, Hispanic parturients
      had 0.5 cm greater cervical dilation compared to non-Hispanic Whites, which was
      not significant (95% confidence interval, -0.1 to 1.1; P = 0.089). CONCLUSIONS:
      Our data indicate that ethnicity/race plays a small role in acceptance and
      request for neuraxial labor analgesia.

PMID- 24854872
TI  - Emergency pages using a computer-based anesthesiology paging system in ambulatory
      surgical centers: a retrospective review.
AB  - BACKGROUND: The nature of pages associated with periprocedural emergency events
      in ambulatory centers has never being examined. Our institution has a proprietary
      anesthesiology paging system with hierarchical paging capabilities (emergency
      versus routine) and maintains a log of all events. Here, we describe emergency
      pages in our ambulatory surgery centers. METHODS: We identified all emergency
      page activations between June 1, 2008, and December 31, 2012, in our ambulatory
      surgical centers. Electronic medical records were reviewed for rates and
      characteristics of pages such as primary cause, interventions performed, and
      outcomes. RESULTS: During the study time frame, 120,618 procedures were performed
      and 93 emergency pages were recorded (7.7 per 10,000 cases, 95% confidence
      interval, 6.2-9.4), of which 51 originated in the procedure room and 42 outside
      the procedure room (16 before and 26 after the procedure). Among those, 14/93
      were associated with serious events (1.2 per 10,000 cases). Among emergency pages
      for bradyarrhythmias (N = 35, 2.9 per 10,000 cases), 15 occurred during IV line
      placement in the preprocedural area, 11 during postprocedural recovery, and 9
      during the procedure. Bradyarrhythmias accounted for 60.4% of pages outside the
      procedural room. In contrast, respiratory and airway events (N = 31, 2.6 per
      10,000 cases) typically occurred in the procedural room (28 vs 9, P = 0.0006).
      Only 1 patient sustained permanent injury, myocardial infarction, and death 4
      months later. Another patient died after 8 days from unrelated causes.
      CONCLUSION: The rates of emergency page activations, especially those that are
      critical events, in our surgical ambulatory center are rare. Many emergency pages
      originated outside the procedural room; therefore, providers within these areas
      should be trained to promptly recognize and treat these events.

PMID- 24854873
TI  - Anterior-posterior versus anterior-lateral electrode position for external
      electrical cardioversion of atrial fibrillation: a meta-analysis of randomized
      controlled trials.
AB  - BACKGROUND: Several clinical trials have shown inconsistent results regarding the
      effect of electrode positions on the success of electrical cardioversion. AIMS:
      The aim of this meta-analysis was to investigate the effect of the anterior
      posterior electrode position on the success of electrical cardioversion in
      patients undergoing external electrical cardioversion for atrial fibrillation.
      METHODS: Pubmed, EMBASE, the Cochrane Library and the Chinese National Knowledge
      Infrastructure were searched for randomized controlled trials. The effect of the
      anterior-posterior electrode position on cardioversion success is presented as a
      risk ratio with 95% confidence interval. RESULTS: Ten trials with 1281 patients
      were included in the analysis. The anterior-posterior electrode position had no
      advantages in terms of success of electrical cardioversion for atrial
      fibrillation compared with the anterior-lateral electrode position (risk ratio
      1.02, 95% confidence interval 0.96-1.09; P=0.50). Subgroup analysis showed that
      patients with a left atrium diameter<=45 mm and lone atrial fibrillation might
      derive benefits from the anterior-posterior electrode position in terms of
      success of cardioversion. No evidence of publication bias was detected.
      CONCLUSIONS: The present analysis suggests that only patients with a left atrium
      diameter<=45 mm and lone atrial fibrillation might derive benefits from the
      anterior-posterior electrode position compared with the anterior-lateral
      electrode position during external electrical cardioversion for atrial
      fibrillation. However, there was insufficient evidence to support any advantages
      for the anterior-posterior electrode position in other situations.

PMID- 24854875
TI  - Polylysine crosslinked AIE dye based fluorescent organic nanoparticles for
      biological imaging applications.
AB  - Fluorescent organic nanoparticles based on aggregation induced emission dyes are
      fabricated through a ring-opening reaction using polylysine as the linker. The
      fluorescent organic nanoparticles obtained are characterized by a series of
      techniques including UV-vis absorption spectroscopy, fluorescence spectroscopy,
      Fourier Transform infrared spectroscopy, and transmission electron microscopy. A
      biocompatibility evaluation and the cell uptake behavior of the fluorescent
      organic nanoparticles are further investigated to evaluate their potential
      biomedical applications. It is demonstrated that these fluorescent organic
      nanoparticles can be obtained at room temperature in an air atmosphere without
      the need for catalyst or initiator. Furthermore, these crosslinked aggregation
      induced emission dye based fluorescent organic nanoparticles show uniform
      morphology, strong red fluorescence, high water dispersability, and excellent
      biocompatibility, making them promising candidates for various biomedical
      applications. 

PMID- 24854876
TI  - Positive selection for bone morphogenetic protein receptor type-IB promotes
      differentiation and specification of human adipose-derived stromal cells toward
      an osteogenic lineage.
AB  - BACKGROUND: Adipose tissue represents an abundant and easily accessible source of
      multipotent cells that may serve as an excellent building block for tissue
      engineering. However, adipose-derived stromal cells (ASCs) are a heterogeneous
      group and subpopulations may be identified with enhanced osteogenic potential.
      METHODS: Human ASC subpopulations were prospectively isolated based on expression
      of bone morphogenetic protein receptor type-IB (BMPR-IB). Unsorted, BMPR-IB(+),
      and BMPR-IB(-) cells were analyzed for their osteogenic capacity through
      histological staining and gene expression. To evaluate their in vivo osteogenic
      potential, critical-sized calvarial defects were created in immunocompromised
      mice and treated with unsorted, BMPR-IB(+), or BMPR-IB(-) cells. Healing was
      assessed using microcomputed tomography and pentachrome staining of specimens at
      8 weeks. RESULTS: Increased osteogenic differentiation was noted in the BMPR
      IB(+) subpopulation, as demonstrated by alkaline phosphatase staining at day 7
      and extracellular matrix mineralization with Alizarin red staining at day 14.
      This was also associated with increased expression for osteocalcin, a late marker
      of osteogenesis. Radiographic analysis demonstrated significantly enhanced
      healing of critical-sized calvarial defects treated with BMPR-IB(+) ASCs compared
      with unsorted or BMPR-IB(-) cells. This was confirmed through pentachrome
      staining, which revealed more robust bone regeneration in the BMPR-IB(+) group.
      CONCLUSION: BMPR-IB(+) human ASCs have an enhanced ability to form bone both in
      vitro and in vivo. These data suggest that positive selection for BMPR-IB(+) and
      manipulation of the BMP pathway in these cells may yield a highly osteogenic
      subpopulation of cells for bone tissue engineering.

PMID- 24854878
TI  - 1H and 13C NMR scaling factors for the calculation of chemical shifts in commonly
      used solvents using density functional theory.
AB  - Calculation of NMR chemical shifts and coupling constants using quantum
      mechanical calculations [density functional theory (DFT)], has become a very
      popular tool for the determination of conformation and the assignment of
      stereochemistry within a molecule. We present the scaling factors (linear
      regression parameters) from 10 DFT methods for 10 commonly used NMR solvents
      using the same set of reference compounds. The results were compared with the
      corresponding gas-phase calculations to assess the inclusion of the polarizable
      continuum model for solvent effects.

PMID- 24854877
TI  - The factor structure and presentation of depression among HIV-positive adults in
      Uganda.
AB  - Depression is one of the most prevalent psychiatric comorbidities of HIV and one
      of the greatest barriers to HIV self-care and adherence. Despite this, little
      consensus exists on how to best measure depression among people living with
      HIV/AIDS (PLWHA) in African settings. Measurement of depression among PLWHA may
      be confounded by somatic symptoms. Some research recommends excluding these items
      to enhance measurement validity; sensitivity may be lost with this approach. We
      sought to characterize depression among a cohort (N = 453) of PLWHA initiating
      antiretroviral therapy in Uganda via factor analysis of a widely used measure of
      depression, the Hopkins Symptom Checklist (HSCLD). Common factor analysis was
      performed, associations between HSCLD and the Mental Health subscale of the
      Medical Outcomes Study HIV (MOS-HIV) estimated, and a Cronbach's alpha calculated
      to examine validity. Factor analysis yielded two factors: (1) somatic-cognitive
      symptoms and (2) behavioral disengagement. Persons with more versus less advanced
      disease (CD4 cell count of <=200 cells/mm(3)) showed no statistically significant
      differences in depression scores (1.7 vs. 1.7, P >= 0.5). Both factors were
      significantly associated with the MOS-HIV (P < .01). Factor one was highly
      reliable (alpha = .81); factor two had only modest reliability (alpha = .65).
      Somatic-cognitive symptoms of depression and disengagement from life's activities
      appear to be distinct components of depression in this sample. Consideration of
      somatic items may be valuable in identifying depression in this setting.

PMID- 24854879
TI  - Inhibitor of differentiation 3, a transcription factor, regulates hyperlipidemia
      associated kidney disease.
AB  - BACKGROUND: Lipoprotein abnormalities are associated with a rapid decline in
      renal function in patients of chronic kidney disease. In addition, hyperlipidemia
      is associated with an increased risk of developing renal insufficiency. The
      underlying molecular mechanisms for these clinical findings are unclear. We have
      previously reported a role for inhibitor of differentiation 3 (ID3), a
      transcription factor, in regulating kidney disease in hyperlipidemia. Introducing
      a genetic deficiency of Id3 in spontaneously hyperlipidemic apolipoprotein E
      knockout (Apoe(-/-)) mice led to accelerated mesangioproliferative
      glomerulonephritis. The present study was carried out to further investigate the
      contribution of ID3 in hyperlipidemia-associated kidney disease. METHODS: Female
      C57BL/6 mice that were ID3-sufficient wild-type (WT) or ID3-deficient (Id3(-/-))
      were fed a Western diet and evaluated for proteinuria, glomerular pathology, and
      immune infiltrating cells. Primary mesangial cell lines were generated from both
      mouse strains and stimulated with oxidized phospholipids. Cytokines and
      chemokines produced were measured by multiplex assays, ELISA, and QPCR.
      Glomerular isolates were studied for CXCL1 expression by QPCR. RESULTS: Id3(-/-)
      mice on a Western diet developed accelerated proteinuria and
      mesangioproliferative glomerulonephritis compared to WT controls. In vitro, Id3(
      /-) glomerular mesangial cell lines produced higher levels of the monocyte
      chemoattractant CXCL1 in response to oxidized phospholipids. This was consistent
      with the rapid increase in glomerular CXCL1 expression followed by macrophage
      infiltration in Id3(-/-) mice fed a Western diet. CONCLUSIONS: A functional ID3
      influences susceptibility to kidney disease and prevents glomerular injury by
      regulating local chemokine production and inflammatory cell recruitment.

PMID- 24854880
TI  - Lipopolysaccharide-regulated production of bone sialoprotein and interleukin-8 in
      human periodontal ligament fibroblasts: the role of toll-like receptors 2 and 4
      and the MAPK pathway.
AB  - BACKGROUND AND OBJECTIVE: Lipopolysaccharide (LPS) on the cell wall of
      periodontal pathogens is a major mediator of the inflammatory response and can
      enhance alveolar bone resorption in periodontitis. Bone sialoprotein is an early
      marker of osteoblast differentiation. The proinflammatory cytokine, interleukin-8
      (IL-8), induces osteoclast differentiation, maturation and maintenance of bone
      resorption activity. However, the effects of LPS from periodontal pathogens on
      the expression of bone sialoprotein and IL-8 in human osteoblasts and the
      mechanism of periodontal bone metabolism regulation are rather unclear. The
      objectives of this study were to determine the effects of Porphyromonas
      gingivalis LPS on the production of bone sialoprotein and IL-8 in human
      periodontal ligament fibroblasts (hPDLFs), and to investigate whether toll-like
      receptor (TLR) 2, TLR4 and MAPKs pathways are involved in the regulation of
      production of bone sialoprotein and IL-8 by P. gingivalis LPS. MATERIAL AND
      METHODS: The third-generation of hPDLFs were cultured with mineralization
      inducing culture medium. After hPDLFs were treated with P. gingivalis LPS, bone
      sialoprotein and IL-8 mRNA expression were detected using Real time PCR. Then
      hPDLFs were transiently transfected with siTLR2 or siTLR4 (20 nm) or inhibited by
      MAPK signaling pathways inhibitors, and then bone sialoprotein and IL-8 mRNA and
      protein expression were also detected using Real time PCR and western blotting.
      RESULTS: Treatments with 0.01 and 0.1 mg/L of P. gingivalis LPS for 8 h up
      regulated bone sialoprotein mRNA expression, whereas 10 and 100 mg/L of P.
      gingivalis LPS induced a significant decrease in the expression of bone
      sialoprotein mRNA. In contrast, IL8 mRNA levels were increased significantly by
      10 mg/L of P. gingivalis LPS. Interestingly, small interfering RNA (siRNA) knock
      down of the TLR2 and ERK1/2 inhibitor, PD98059, abolished the effects of P.
      gingivalis LPS on the bone sialoprotein mRNA level, whereas siRNA knock down of
      the TLR2 and p38 MAPK inhibitor, SB203580, blocked the effect of P. gingivalis
      LPS on IL-8 in hPDLFs. CONCLUSION: This study suggests that in hPDLFs, P.
      gingivalis LPS suppresses bone sialoprotein and enhances IL-8 gene and protein
      expression via TLR2 and ERK1/2 or the p38 MAPK signaling pathway, respectively.

PMID- 24854881
TI  - Personality disturbances in amyotrophic lateral sclerosis: a case study
      demonstrating changes in personality without cognitive deficits.
AB  - Patients with amyotrophic lateral sclerosis (ALS) often show deficits on
      neuropsychological tests that tap functions related to the integrity of the
      prefrontal lobes. Various aspects of personality are also known to be mediated by
      prefrontal regions, particularly ventromedial prefrontal cortex (vmPFC). Other
      than apathy, personality changes have not been widely reported in patients with
      ALS, although clinical observations indicate such changes might be relatively
      common. Here, we report on a middle-aged woman with bulbar onset ALS (diagnosed
      06/2011, examined in Spring, 2012) whose neuropsychological exam did not reveal
      cognitive deficits. She performed normally on tests of executive functioning.
      Self-report measures of mood and personality were unremarkable. However,
      significant personality changes subsequent to disease onset were reported by her
      husband and two daughters, and these changes were quantified with the Iowa Scales
      of Personality Change. Results show that personality disturbance may manifest in
      the absence of notable cognitive changes in ALS, and careful assessment of
      personality may be important for documenting early neurobehavioral changes in
      some ALS patients. Findings also show that patients with ALS may not have good
      insight into personality changes, underscoring the importance of acquiring
      collateral information. More generally, the results provide further evidence that
      ALS may compromise the integrity of ventromedial prefrontal regions.

PMID- 24854883
TI  - Hair dermatophytosis diagnosed by reflectance confocal microscopy: six cases.

PMID- 24854882
TI  - Neurocognitive risk in children with cochlear implants.
AB  - IMPORTANCE: Children who receive a cochlear implant (CI) for early severe to
      profound sensorineural hearing loss may achieve age-appropriate spoken language
      skills not possible before implantation. Despite these advances, reduced access
      to auditory experience may have downstream effects on fundamental neurocognitive
      processes for some children with CIs. OBJECTIVE: To determine the relative risk
      (RR) of clinically significant executive functioning deficits in children with
      CIs compared with children with normal hearing (NH). DESIGN, SETTING, AND
      PARTICIPANTS: In this prospective, cross-sectional study, 73 children at a
      hospital-based clinic who received their CIs before 7 years of age and 78
      children with NH, with average to above average mean nonverbal IQ scores, were
      recruited in 2 age groups: preschool age (age range, 3-5 years) and school age
      (age range, 7-17 years). No children presented with other developmental,
      cognitive, or neurologic diagnoses. INTERVENTIONS: Parent-reported checklist
      measures of executive functioning were completed during psychological testing
      sessions. MAIN OUTCOMES AND MEASURES: Estimates of the RR of clinically
      significant deficits in executive functioning (>=1 SDs above the mean) for
      children with CIs compared with children with NH were obtained based on 2 parent
      reported child behavior checklists of everyday problems with executive
      functioning. RESULTS: In most domains of executive functioning, children with CIs
      were at 2 to 5 times greater risk of clinically significant deficits compared
      with children with NH. The RRs for preschoolers and school-aged children,
      respectively, were greatest in the areas of comprehension and conceptual learning
      (RR [95% CI], 3.56 [1.71-7.43] and 6.25 [2.64-14.77]), factual memory ( 4.88
      [1.58-15.07] and 5.47 [2.03-14.77]), attention (3.38 [1.03-11.04] and 3.13 [1.56
      6.26]), sequential processing (11.25 [1.55-81.54] and 2.44 [1.24-4.76]), working
      memory (4.13 [1.30-13.06] and 3.64 [1.61-8.25] for one checklist and 1.77 [0.82
      3.83] and 2.78 [1.18-6.51] for another checklist), and novel problem-solving
      (3.93 [1.50-10.34] and 3.13 [1.46-6.67]). No difference between the CI and NH
      samples was found for visual-spatial organization (2.63 [0.76-9.03] and 1.04
      [0.45-2.40] on one checklist and 2.86 [0.98-8.39] for school-aged children on the
      other checklist). CONCLUSIONS AND RELEVANCE: A large proportion of children with
      CIs are at risk for clinically significant deficits across multiple domains of
      executive functioning, a rate averaging 2 to 5 times that of children with NH for
      most domains. Screening for risk of executive functioning deficits should be a
      routine part of the clinical evaluation of all children with deafness and CIs.

PMID- 24854884
TI  - In vitro and in vivo topical delivery studies of tretinoin-loaded ultradeformable
      vesicles.
AB  - INTRODUCTION: Ultradeformable vesicles are highly promising tools to enhance the
      percutaneous transport of different drugs such as tretinoin across the skin
      barrier and also to increase the formulation stability at absorption site and
      reduce the drug induced irritation. METHODS: Topical delivery of tretinoin-loaded
      ultradeformable vesicles (tretinoin-UDV) was evaluated concerning different
      studies, such as: the release and permeation profiles (tape stripping); skin
      penetration (fluorescence analysis); induced electrical changes in skin barrier
      properties; cytotoxicity (Trypan Blue assay) and skin irritation in in vivo
      conditions (Draize test). The novel formulation performance was also compared to
      a commercial tretinoin formulation regarding in vivo studies. RESULTS: It was
      obtained a sustained and controlled drug release, as expected for UDV
      formulation. In addition, a dermal delivery was observed regarding the permeation
      study since it was not detected any drug amount in the receptor phase after 24h.
      Nile Red-UDV stained intensively mostly in the stratum corneum, corroborating the
      tape stripping results. Tretinoin-UDV decreased skin resistance, suggesting its
      ability to induce skin barrier disruption. Finally, the formulation vehicle
      (empty UDV) and tretinoin-UDV were not toxic under in vitro and in vivo
      conditions, at least, at 5*10(-3)mg/mL and 0.5mg/mL of tretinoin, respectively.
      CONCLUSION: Tretinoin-UDV is a promising delivery system for tretinoin dermal
      delivery without promoting skin irritation (unlike other commercial
      formulations), which is quite advantageous for therapeutic purpose.

PMID- 24854874
TI  - A global analysis of Y-chromosomal haplotype diversity for 23 STR loci.
AB  - In a worldwide collaborative effort, 19,630 Y-chromosomes were sampled from 129
      different populations in 51 countries. These chromosomes were typed for 23 short
      tandem repeat (STR) loci (DYS19, DYS389I, DYS389II, DYS390, DYS391, DYS392,
      DYS393, DYS385ab, DYS437, DYS438, DYS439, DYS448, DYS456, DYS458, DYS635, GATAH4,
      DYS481, DYS533, DYS549, DYS570, DYS576, and DYS643) and using the PowerPlex Y23
      System (PPY23, Promega Corporation, Madison, WI). Locus-specific allelic spectra
      of these markers were determined and a consistently high level of allelic
      diversity was observed. A considerable number of null, duplicate and off-ladder
      alleles were revealed. Standard single-locus and haplotype-based parameters were
      calculated and compared between subsets of Y-STR markers established for forensic
      casework. The PPY23 marker set provides substantially stronger discriminatory
      power than other available kits but at the same time reveals the same general
      patterns of population structure as other marker sets. A strong correlation was
      observed between the number of Y-STRs included in a marker set and some of the
      forensic parameters under study. Interestingly a weak but consistent trend toward
      smaller genetic distances resulting from larger numbers of markers became
      apparent. 

PMID- 24854886
TI  - Impact of sleep-disordered breathing treatment on upper airway anatomy and
      physiology.
AB  - Sleep-disordered breathing (SDB) is a major public health problem. Various
      anatomic, pathophysiologic, and environmental changes contribute to SDB. The
      successful treatment of SDB reverses many of these abnormal processes. The
      present article discusses the current clinical evidence that supports the
      reversibility and its potential application in the management of SDB. Continuous
      positive airway pressure reduces angiogenesis and inflammatory edema, increases
      pharyngeal size, and improves surrogate markers of vascular inflammation and
      tongue muscle fiber types. Mandibular advancement devices lead to favorable
      maxillary and mandibular changes, increase pharyngeal area, and improve
      hypertension. Uvulopalatopharyngoplasty increases posterior airway space and
      pharyngeal volume, reduces nasal and oral resistance, and lowers response to high
      CO2. Weight loss reduces nasopharyngeal collapsibility, critical closing pressure
      of the airway, apnea-hypopnea index, and improves oxygen saturations. Potential
      clinical benefits of these changes in the management of SDB and patient
      compliance with treatment are discussed. 

PMID- 24854885
TI  - A reduced dimensionality NMR pulse sequence and an efficient protocol for
      unambiguous assignment in intrinsically disordered proteins.
AB  - Resonance assignment in intrinsically disordered proteins poses a great challenge
      because of poor chemical shift dispersion in most of the nuclei that are commonly
      monitored. Reduced dimensionality (RD) experiments where more than one nuclei are
      co-evolved simultaneously along one of the time axes of a multi-dimensional NMR
      experiment help to resolve this problem partially, and one can conceive of
      different combinations of nuclei for co-evolution depending upon the
      magnetization transfer pathways and the desired information content in the
      spectrum. Here, we present a RD experiment, (4,3)D-hNCOCAnH, which uses a
      combination of CO and CA chemical shifts along one of the axes of the 3
      dimensional spectrum, to improve spectral dispersion on one hand, and provide
      information on four backbone atoms of every residue-HN, N, CA and CO chemical
      shifts-from a single experiment, on the other. The experiment provides multiple
      unidirectional sequential (i -> i - 1) amide (1)H correlations along different
      planes of the spectrum enabling easy assignment of most nuclei along the protein
      backbone. Occasional ambiguities that may arise due to degeneracy of amide proton
      chemical shifts are proposed to be resolved using the HNN experiment described
      previously (Panchal et al. in J Biomol NMR 20:135-147, 2001). Applications of the
      experiment and the assignment protocol have been demonstrated using intrinsically
      disordered alpha-synuclein (140 aa) protein.

PMID- 24854887
TI  - Effects of pitolisant, a histamine H3 inverse agonist, in drug-resistant
      idiopathic and symptomatic hypersomnia: a chart review.
AB  - OBJECTIVE: To evaluate the benefits and risks of pitolisant (a wake-enhancing
      drug that increases the histamine release in the brain by blocking presynaptic H3
      histamine reuptake) in patients with idiopathic (IH) and symptomatic (SH)
      hypersomnia plus sleepiness refractory to available stimulants (modafinil,
      methylphenidate, mazindol, sodium oxybate, and d-amphetamine). METHODS: Through
      retrospective analyses of patient files, the benefit (the score from the Epworth
      Sleepiness Scale [ESS], authorization renewal) and tolerance (side-effects) of
      pitolisant were assessed. RESULTS: A total of 78 patients with IH (n=65%, 78%
      women) and SH (n=13%, 54% women) received pitolisant 5-50 mg once per day over
      the course of five days to 37 months. The median (interquartile range) ESS scores
      of patients with IH decreased from 17 (15.5-18.5) to 14 (12-17). There were 36%
      responders (ESS fall of > or =3). The improvement in ESS score (-1.9+/-2.6) was
      different from 0 in IH without long sleep time (P<0.002) and in IH with a long
      sleep time (P<0.0001), but not in SH. Forty-four (63%) patients with IH and 12
      (77%) patients with SH stopped pitolisant, mostly due to a lack of efficacy. Side
      effects included gastrointestinal pain (15.4%), increased appetite and weight
      gain (14.1%), headache (12.8%), insomnia (11.5%), and anxiety (9%), as well as
      exceptional reports of depression and persistent genital arousal. CONCLUSION:
      Pitolisant had a long-term favorable benefit/risk ratio in 23-38% of drug
      resistant patients with IH and SH, suggesting that histamine neurons can be
      stimulated in severe idiopathic and symptomatic hypersomnia.

PMID- 24854889
TI  - Intramolecular N-H...Cl hydrogen bonds in the outer coordination sphere of a
      bipyridyl bisurea-based ligand stabilize a tetrahedral FeLCl2 complex.
AB  - A bipyridyl-based anion receptor is utilized as a ligand in a tetrahedral FeCl2
      complex and demonstrates secondary coordination sphere influence through
      intramolecular hydrogen bonding to the chloride ligands as evidenced by X-ray
      crystallography. 

PMID- 24854888
TI  - Biofunctional nanofibrous substrate comprising immobilized antibodies and
      selective binding of autologous growth factors.
AB  - The immobilization of biomolecules at the surface of different biomedical devices
      has attracted enormous interest in order to enhance their biological
      functionality at the cellular level. This work aims to develop a biofunctional
      polymeric substrate capable of selectively binding growth factors (GFs) of
      interest from a pool of proteins present in a biological fluid: platelet lysate
      (PL). To achieve this goal, the surface of electrospun PCL nanofibers needs to be
      activated and functionalized to be able to insert chemical groups for the
      immobilization of antibodies. After determining the maximum immobilization
      capacity of each antibody, TGF-beta1 (12 MUg mL(-1)), bFGF (8 MUg mL(-1)), and
      VEGF (4 MUg mL(-1)), the next step was to confirm their bioavailability using
      recombinant proteins. The binding efficiency of PL-derived GFs was of 84-87% for
      TGF-beta1, 55-64% for bFGF, and 50-59% for VEGF. Cellular assays confirmed the
      biological activity of the bound VEGF (both recombinant and PL-derived). Multiple
      antibodies (i.e., bFGF and VEGF) were also immobilized over the same structure in
      a mixed or side-by-side fashion. Using both autologous biological fluids and
      cells, it is possible to use this platform to implement very effective and
      personalized therapies that can be tailored to specific medical conditions. 

PMID- 24854891
TI  - Fast separation, characterization, and speciation of gold and silver
      nanoparticles and their ionic counterparts with micellar electrokinetic
      chromatography coupled to ICP-MS.
AB  - In this study, a method for separation, size characterization, and speciation of
      gold and silver nanoparticles was developed through the use of micellar
      electrokinetic chromatography (MEKC) coupled to inductively coupled plasma-mass
      spectrometry (ICP-MS) for the first time. Figures of merit in this proof-of
      principle study include peak area precision of 4-6%, stable migration times (1.4%
      with internal standard), and capillary recoveries on the order of 72-100%
      depending on species and nanoparticle size, respectively. Detection limits are
      currently in the sub-microgram per liter range. For example, a total of 1500 50
      nm-sized gold nanoparticles were successfully detected. After careful
      optimization, MEKC-ICP-MS was used to separate engineered nanoparticles (ENPs) of
      different composition. Speciation analysis of ENPs and free metal ions in
      solution was feasible using a complexing agent (penicillamine). Gold speciation
      analysis of a dietary supplement, which contained approximately 6-nm-sized gold
      nanoparticles, was demonstrated. 

PMID- 24854890
TI  - Endocrinopathies in Turkish children with Beta thalassemia major: results from a
      single center study.
AB  - The endocrinological complications in beta-thalassemia major patients do affect
      the life quality to a large extend. In this study, the endocrinological
      complications of 47 beta-thalassemia patients, who have been followed-up at our
      hospital's pediatric hematology department, were evaluated. Out of beta
      thalassemia major cases included to this study, the 55.3% was male and 44.7% was
      female. The patients' mean levels of ferritin, whose mean age was 10.0 +/- 4.5
      years (2-20 years), were 2497 +/- 1469 ng/mL (472-8558 ng/mL). At least one
      endocrinological pathology in 27 out of 47 (57.4%) and more than one
      endocrinological pathology in 14 out of 47 (29.7%) thalassemia patients were
      observed. The most frequently observed complication in followed-up cases was
      vitamin D insufficiency and deficiency (78.2%). The other complications in
      decreasing order were pubertal failure (41.6%), growth retardation (25.5%),
      decreased bone-mineral density (22.2%), secondary hyperparathyroidism (11.5%),
      overt hypothyroidism (4.25%), subclinical hypothyroidism (2.12%), and impaired
      glucose tolerance (2.12%). There was no statistically significant difference
      between serum mean ferritin level and endocrin complications (P > .05). Four
      patients (8.5%) had decreased signal intensity in pituitary magnetic resonance
      imaging (MRI) but this finding was not associated with ferritin levels (P = .87).
      MRI parameters were similar between patients with and without gonadal
      dysfunction. Mean height of the pituitary gland was 4.98 +/- 1.1 mm (3-9 mm) and
      this was similar to those normal values in the literature. Ferritin levels were
      not correlated with pituitary height (P > .05). Beta thalassemia major, having
      the potential of leading to multisystemic complications, is a chronic disease
      that should be treated and followed-up by a multidisciplinary approach. Due to
      frequently encountered endocrinological complications, beta thalassemic patients
      should be followed-up regularly by hematology and endocrinology departments in
      coordination. 

PMID- 24854892
TI  - Mechanistic modeling of monocarboxylate transporter-mediated
      toxicokinetic/toxicodynamic interactions between gamma-hydroxybutyrate and L
      lactate.
AB  - Overdose of gamma-hydroxybutyrate (GHB) can result in severe respiratory
      depression. Monocarboxylate transporter (MCT) inhibitors, including L-lactate,
      increase GHB clearance and represent a potential treatment for GHB intoxication.
      GHB can also affect L-lactate clearance, and L-lactate has been reported to
      affect respiration. In this research, we characterize these
      toxicokinetic/toxicodynamic interactions between GHB and L-lactate using
      mechanistic modeling. Plasma, urine, and respiration data were taken from our
      previous study in which GHB and sodium L-lactate were administered alone and
      concomitantly in rats. A model incorporating active renal reabsorption for both
      agents fit GHB and L-lactate toxicokinetic data. The Km for renal reabsorption of
      GHB (650 MUg/mL) was close to its Km for the proton-dependent MCT1 and that for L
      lactate (13.5 MUg/mL) close to its Km for the sodium-dependent SMCT1. Inhibition
      of reabsorption by both agents was necessary to model concomitant drug
      administration. The metabolic Km for L-lactate closely resembled that for MCT
      mediated hepatic uptake in vitro, and GHB inhibited this process. L-lactate
      significantly inhibited respiration at a high dose, and an indirect response
      model was used to fit these data. GHB toxicodynamics was modeled as a direct
      effect delayed by nonlinear transport into the brain extracellular fluid, with a
      Km value of 1,865 MUg/mL for brain uptake which is similar to the in vitro Km
      value determined in rat brain endothelial cells. This model was useful for
      characterizing multiple MCT-mediated interactions. Incorporation of many
      parameters that can be determined in vitro may allow for clinical translation of
      these interactions.

PMID- 24854893
TI  - Understanding pharmaceutical quality by design.
AB  - This review further clarifies the concept of pharmaceutical quality by design
      (QbD) and describes its objectives. QbD elements include the following: (1) a
      quality target product profile (QTPP) that identifies the critical quality
      attributes (CQAs) of the drug product; (2) product design and understanding
      including identification of critical material attributes (CMAs); (3) process
      design and understanding including identification of critical process parameters
      (CPPs), linking CMAs and CPPs to CQAs; (4) a control strategy that includes
      specifications for the drug substance(s), excipient(s), and drug product as well
      as controls for each step of the manufacturing process; and (5) process
      capability and continual improvement. QbD tools and studies include prior
      knowledge, risk assessment, mechanistic models, design of experiments (DoE) and
      data analysis, and process analytical technology (PAT). As the pharmaceutical
      industry moves toward the implementation of pharmaceutical QbD, a common
      terminology, understanding of concepts and expectations are necessary. This
      understanding will facilitate better communication between those involved in risk
      based drug development and drug application review.

PMID- 24854894
TI  - Measurement of subvisible particulates in lyophilised Erwinia chrysanthemi L
      asparaginase and relationship with clinical experience.
AB  - In order to generate further characterisation data for the lyophilised product
      Erwinia chrysanthemi L-asparaginase, reconstituted drug product (DP; marketed as
      Erwinase or Erwinaze) was analysed for subvisible (2-10 MUm) particulate content
      using both the light obscuration (LO) method and the newer flow-imaging
      microscopy (FIM) technique. No correlation of subvisible particulate counts
      exists between FIM and LO nor do the counts correlate with activity at both
      release and on stability. The subvisible particulate content of lyophilised
      Erwinia L-asparaginase appears to be consistent and stable over time and in line
      with other parenteral biopharmaceutical products. The majority (ca. 75%) of
      subvisible particulates in L-asparaginase DP were at the low end of the
      measurement range by FIM (2-4 MUm). In this size range, FIM was unable to
      definitively classify the particulates as either protein or non-protein. More
      sensitive measurement techniques would be needed to classify the particulates in
      lyophilised L-asparaginase into type (protein and non-protein), so the LO
      technique has been chosen for on-going DP analyses. E. chrysanthemi L
      asparaginase has a lower rate of hypersensitivity compared with native
      Escherichia coli preparations, but a subset of patients develop hypersensitivity
      to the Erwinia enzyme. A DP lot that had subvisible particulate counts on the
      upper end of the measurement range by both LO and FIM had the same incidence of
      allergic hypersensitivity in clinical experience as lots at all levels of
      observed subvisible particulate content, suggesting that the presence of L
      asparaginase subvisible particulates is not important with respect to allergic
      response.

PMID- 24854896
TI  - Permeability comparison between hepatocyte and low efflux MDCKII cell monolayer.
AB  - Determination of passive permeability is not only important for predicting oral
      absorption and brain penetration, but also for accurately predicting hepatic
      clearance. High throughput (HT) measurement of passive permeability across
      hepatocyte cell membrane is technically more challenging than using monolayer
      cell-based permeability assays. In this study, we evaluated if the HT Madin-Darby
      canine kidney II-low efflux (MDCKII-LE) cell monolayer permeability assay can be
      used as a surrogate to predict the passive permeability of hepatocytes. Apparent
      passive permeability of MDCKII-LE is well correlated to passive diffusion
      clearance of human and rat hepatocytes, suggesting that the HT MDCKII-LE assay
      can be used as a surrogate to estimate the passive permeability of hepatocytes.
      In addition, lipophilicity (Log D determined at pH 7.4) was also found to be well
      correlated with both MDCKII-LE and hepatocyte permeability for most compounds,
      hence it may serve as another permeability surrogate.

PMID- 24854895
TI  - Statistical comparison of dissolution profiles to predict the bioequivalence of
      extended release formulations.
AB  - Appropriate setting of dissolution specification of extended release (ER)
      formulations should include precise definition of a multidimensional space of
      complex definition and interpretation, including limits in dissolution
      parameters, lag time (t-lag), variability, and goodness of fit. This study aimed
      to set dissolution specifications of ER by developing drug-specific dissolution
      profile comparison tests (DPC tests) that are able to detect differences in
      release profiles between ER formulations that represent a lack of bioequivalence
      (BE). Dissolution profiles of test formulations were simulated using the Weibull
      and Hill models. Differential equations based in vivo-in vitro correlation
      (IVIVC) models were used to simulate plasma concentrations. BE trial simulations
      were employed to find the formulations likely to be declared bioequivalent and
      nonbioequivalent (BE space). Customization of DPC tests was made by adjusting the
      delta of a recently described tolerated difference test (TDT) or the limits of
      rejection of f2. Drug ka (especially if ka is small), formulation lag time (t
      lag), the number of subjects included in the BE studies, and the number of
      sampled time points in the DPC test were the factors that affected the most these
      setups of dissolution specifications. Another recently described DPC test,
      permutation test (PT), showed excellent statistical power. All the formulations
      declared as similar with PT were also bioequivalent. Similar case-specific
      studies may support the biowaiving of ER drug formulations based on customized
      DPC tests.

PMID- 24854897
TI  - Patterns of utilization of complementary and alternative medicine in 2 pediatric
      gastroenterology clinics.
AB  - OBJECTIVES: The aim of the present study was to assess the prevalence and
      patterns of complementary and alternative medicine (CAM) use among pediatric
      patients with gastrointestinal (GI) disorders at academic clinics in Canada.
      METHODS: The survey was carried out at 2 hospital-based gastroenterology clinics:
      the Stollery Children's Hospital in Edmonton and the Children's Hospital of
      Eastern Ontario (CHEO) in Ottawa. RESULTS: CAM use at the Stollery was 83%
      compared with 36% at CHEO (P < 0.001). The most common reason for not using CAM
      was lack of knowledge about it. Most respondents felt comfortable discussing CAM
      in their clinic and wanted more information on CAM. The most common CAM products
      being taken were multivitamins (91%), calcium (35%), vitamin C (32%), probiotics
      (14%), and fish oil/omega-3 fatty acids (13%). The most common CAM practices
      being used were massage (43%), chiropractic (27%), faith healing (25%), and
      relaxation (18%). Most respondents believed that CAM was helpful, and most of the
      23 reported adverse effects were minor. Seven were reported as moderate, and 3
      were reported as severe. Many (42%) patients used CAM at the same time as
      prescription medicines, and of these patients, concurrent use was discussed with
      their physician (76%) or pharmacist (52%). CONCLUSIONS: CAM use is high among
      pediatric patients with GI disorders and is much greater among those in Edmonton
      than in Ottawa. Most respondents reported their CAM use as helpful, with little
      or no associated harm. Many patients fail to disclose their concurrent use of CAM
      and conventional medicines to their doctors, increasing the likelihood of
      interactions.

PMID- 24854898
TI  - Discovery of binding proteins for a protein target using protein-protein docking
      based virtual screening.
AB  - Target structure-based virtual screening, which employs protein-small molecule
      docking to identify potential ligands, has been widely used in small-molecule
      drug discovery. In the present study, we used a protein-protein docking program
      to identify proteins that bind to a specific target protein. In the testing
      phase, an all-to-all protein-protein docking run on a large dataset was
      performed. The three-dimensional rigid docking program SDOCK was used to examine
      protein-protein docking on all protein pairs in the dataset. Both the binding
      affinity and features of the binding energy landscape were considered in the
      scoring function in order to distinguish positive binding pairs from negative
      binding pairs. Thus, the lowest docking score, the average Z-score, and
      convergency of the low-score solutions were incorporated in the analysis. The
      hybrid scoring function was optimized in the all-to-all docking test. The docking
      method and the hybrid scoring function were then used to screen for proteins that
      bind to tumor necrosis factor-alpha (TNFalpha), which is a well-known therapeutic
      target for rheumatoid arthritis and other autoimmune diseases. A protein library
      containing 677 proteins was used for the screen. Proteins with scores among the
      top 20% were further examined. Sixteen proteins from the top-ranking 67 proteins
      were selected for experimental study. Two of these proteins showed significant
      binding to TNFalpha in an in vitro binding study. The results of the present
      study demonstrate the power and potential application of protein-protein docking
      for the discovery of novel binding proteins for specific protein targets.

PMID- 24854899
TI  - The rupture of a single liquid aluminium alloy film.
AB  - The present study is based on the idea of understanding the rupture of films in
      metal foams by studying free standing metallic films as a model system. Liquid
      dynamics, the velocity of the rupturing material as well as the behaviour of
      ceramic particles inside the melt were analysed optically ex situ and by
      synchrotron X-ray radiography in situ. It was found that the resistance of films
      to rupture is mainly based on the interaction between solid particles and an
      immobile oxide skin, the formation of which depends on the oxygen content of the
      surrounding atmosphere and the presence of magnesium. 

PMID- 24854900
TI  - Incidence for progression of hypervascular HCC in hypovascular hepatic nodules
      showing hyperintensity on gadoxetic acid-enhanced hepatobiliary phase in patients
      with chronic liver diseases.
AB  - PURPOSE: The purpose of this study was to elucidate the incidence and risk
      factors for the progression of hyperintense nodules, observed in the
      hepatobiliary phase of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic
      acid-enhanced magnetic resonance imaging (Gd-EOB-DTPA-enhanced MRI), to
      hypervascular hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Hypovascular
      nodules (n = 157) showing hyperintensity in the hepatobiliary phase of Gd-EOB
      DTPA-enhanced MRI were examined in 41 patients. All patients underwent computed
      tomography (CT) during hepatic arteriography and CT during arterial portography
      within one month of Gd-EOB-DTPA-enhanced MRI. The incidence of progression to
      hypervascular or classical HCC was calculated using the Kaplan-Meier method.
      RESULTS: Tumor size was determined by univariate and multivariate analysis to be
      an important risk factor of hypervascularization (p = 0.041, odds ratio 1.135).
      The cumulative incidences of hypervascularization in hypovascular nodules showing
      hyperintensity on the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI were 2.4,
      4.5, and 6.2 % at 12, 24, and 36 months, respectively. The incidence of
      hypervascularization was significantly increased in nodules >10 mm in diameter (p
      = 0.00035). CONCLUSION: In patients with chronic liver disease, hypovascular
      nodules presenting as hyperintense in the hepatobiliary phase of Gd-EOB-DTPA
      enhanced MRI and >10 mm in diameter have malignant potential for progression to
      hypervascular HCC and require careful management.

PMID- 24854901
TI  - Re-evaluation of detectability of liver metastases by contrast-enhanced CT: added
      value of hepatic arterial phase imaging.
AB  - PURPOSE: We compared the detectability of liver metastases on 2- and 3-phase
      images using robust statistical methods. Nine radiologists evaluated unenhanced
      CT plus portal venous phase (2-phase) images and 2-phase plus hepatic arterial
      phase (HAP) (3-phase) images. MATERIALS AND METHODS: Our study included 54
      patients with primary malignant tumors who underwent 3-phase hepatic dynamic CT
      more than twice to screen for liver metastases; 24 had 1-6 liver metastases
      measuring 4-27 mm in diameter (median 13 mm). The other 30 had no metastases.
      Nine board-certified radiologists participated in our observer performance study.
      They specified the location of the metastatic lesions and rated the probability
      of metastatic nodules on 2-phase images acquired with and without HAP imaging. We
      used jackknife alternative free-response receiver operating characteristic
      (JAFROC) analysis to compare their performances. RESULTS: For all radiologists
      the area under the curve without and with HAP imaging was 0.86 and 0.88,
      respectively; the difference was significant (p = 0.04). For metastases smaller
      than 10 mm the averaged lesion localization fraction without and with HAP imaging
      was 0.17 and 0.26 (p < 0.01). CONCLUSION: Adding HAP to 2-phase imaging improved
      the detectability of liver metastases, especially of lesions smaller than 10 mm.

PMID- 24854902
TI  - Coronary cameral fistula treated by the Amplatzer vascular plug.
AB  - Coronary artery anomalies occur in less than 1 % of the general population. With
      the advent of multidetector rows and 3D reconstruction, multidetector computed
      tomography has emerged as the modality of choice in the delineation of the
      complex coronary anatomy and diagnosis of coronary artery anomalies, helping in
      the institution of appropriate therapy. We report a case of coronary cameral
      fistula of the left anterior descending artery to the right ventricle, which was
      closed by an Amplatzer vascular plug. Coronary CT angiography was used to
      evaluate the patient prior to the procedure to locate the placement site for the
      vascular plug. 

PMID- 24854904
TI  - [Academic integrity and research misconduct in medical research field].

PMID- 24854903
TI  - Evaluating four-dimensional time-lapse electrical resistivity tomography for
      monitoring DNAPL source zone remediation.
AB  - Practical, non-invasive tools do not currently exist for mapping the remediation
      of dense non-aqueous phase liquids (DNAPLs). Electrical resistivity tomography
      (ERT) exhibits significant potential but has not yet become a practitioner's tool
      due to challenges in interpreting the survey results at real sites. This study
      explores the effectiveness of recently developed four-dimensional (4D, i.e., 3D
      space plus time) time-lapse surface ERT to monitor DNAPL source zone remediation.
      A laboratory experiment demonstrated the approach for mapping a changing NAPL
      distribution over time. A recently developed DNAPL-ERT numerical model was then
      employed to independently simulate the experiment, providing confidence that the
      DNAPL-ERT model is a reliable tool for simulating real systems. The numerical
      model was then used to evaluate the potential for this approach at the field
      scale. Four DNAPL source zones, exhibiting a range of complexity, were initially
      simulated, followed by modeled time-lapse ERT monitoring of complete DNAPL
      remediation by enhanced dissolution. 4D ERT inversion provided estimates of the
      regions of the source zone experiencing mass reduction with time. Results show
      that 4D time-lapse ERT has significant potential to map both the outline and the
      center of mass of the evolving treated portion of the source zone to within a few
      meters in each direction. In addition, the technique can provide a reasonable,
      albeit conservative, estimate of the DNAPL volume remediated with time: 25%
      underestimation in the upper 2m and up to 50% underestimation at late time
      between 2 and 4m depth. The technique is less reliable for identifying cleanup of
      DNAPL stringers outside the main DNAPL body. Overall, this study demonstrates
      that 4D time-lapse ERT has potential for mapping where and how quickly DNAPL mass
      changes in real time during site remediation. 

PMID- 24854906
TI  - [Clinical distribution and antimicrobial resistance analysis of 754 pathogenic
      bacteria in diabetic foot infection].
AB  - OBJECTIVE: To explore the microbiological profiles and antibiotic susceptibility
      patterns of organisms isolated from diabetic foot ulcers so as to provide
      selection rationales of antibiotics. METHODS: A retrospective study was conducted
      on the microbiological profiles and antibiotic susceptibilities in 754 strains of
      pathogens isolated from 519 patients with diabetic foot ulcers at our hospital
      from January 2010 to August 2013. The inter-group data were compared by Chi
      square test. RESULTS: There were 322 (62.0%) males and 197 (38.0%) females. Their
      mean age was (67.7 +/- 12.3) (30-93) years, duration of diabetes 10 (0-40) years,
      duration of lower-limb lesion 1.0 (0.0-72.0) months and HbA1c (9.09% +/- 2.28%).
      Among 444 (85.5%) cases, a total of 754 strains of pathogens were isolated. Gram
      positive aerobes were the most frequently isolated (47.3%, 357 strains) and
      followed by gram-negative aerobes and fungus (40.3% vs 12.3%, 304 vs 93 strains
      respectively). With rising Wagner's grades, bacterial floras transformed from
      Gram-positive cocci to Gram-negative rods while fungus and composite infections
      increased. And 122 strains were of multi drug resistant organisms (MDRO). Among
      357 strains of Gram-positive bacteria, Staphylococcus aureus, Staphylococcus
      epidermidis and Enterococcus faecalis were dominating floras. Staphylococcus was
      highly resistant to penicillin G, erythromycin, and oxacillin while vancomycin
      and linezolid were the most effective agents against gram-positive bacteria.
      Among 304 strains of gram-negative bacteria, enterobacteria were the most
      prevalent, including 48 strains of Escherichia coli, 34 strains of Proteus
      mirabilis and 31 strains of Proteus vulgaris. And there were 29 strains of
      Pseudomonas aeruginosa. Enterobacteria were highly resistant to ampicillin,
      followed by bactrim and furadantin while meropenem, imipenem,
      piperacillin/sulbactam, sulperazone and cefepime were the most effective agents.
      The predominant fungus was Blastomyces albicans. CONCLUSIONS: In patients with
      severe diabetic foot ulcers, Gram-negative rods predominate while the prevalence
      of fungus and composite infections increases. Vancomycin and imipenem maintain
      highly antibacterial activity. It is essential to pay attention to pathogen
      survey and use antibiotics more rationally.

PMID- 24854905
TI  - [Analysis of HIV genotypic drug resistance among pediatric HIV/AIDS cases with
      virological failure after free antiretroviral therapy in Yunnan province].
AB  - OBJECTIVE: To assess the prevalence and the characteristics of HIV-1 drug
      resistance in pediatric HIV/AIDS cases with virological failure after free
      antiretroviral therapy in Yunnan Province. METHODS: The data of clinical test and
      laboratory detection about free antiretroviral therapy in pediatric HIV/AIDS
      cases from 2005 to 2012 were collected. Then the detection of HIV genotypical
      drug resistance was performed for the plasmas samples whose viral load were over
      1 000 copies/ml after the duration of antiretroviral therapy beyond 6 months. The
      prevalence and the characteristics of HIV-1 drug resistance were obtained for
      subsequent analysis. RESULTS: A total of 73 cases suffered virological failure
      among 729 cases while 53 cases exhibited the resistance for antiretroviral
      drugs.So the resistance ratio was 72.6% (53/73) and the general resistance ratio
      7.3% (53/729). The prevalent mutations associated with drug resistance were
      M184V/I, K103N, T215F/Y, G190A, Y181C and K101E at the frequencies of 52.1%
      (38/73), 30.1% (22/73), 21.9% (16/73), 20.5% (15/73), 15.1% (11/73) and 12.3%
      (9/73) respectively. The percentage of resistance to NVP, 3TC, EFV, D4T, AZT and
      ABC was 61.6% (45/73) , 54.8% (40/73) , 47.9% (35/73) , 13.7% (10/73) , 12.3%
      (9/73) and 5.5% (4/73) respectively. One case developed intermediate resistance
      to LPV/r. CONCLUSIONS: The main causes of virological failure is drug
      resistance.So reducing the incidence and spread of HIV drug resistance is of
      vital importance in modern era of resource scarcity.

PMID- 24854907
TI  - [Effects of cigarette smoke on phagocytosed function of monocyte-derived
      macrophage in chronic obstructive pulmonary disease patients].
AB  - OBJECTIVE: To explore the effects of cigarette smoke extract (CSE) on
      phagocytosizing function of monocyte-derived macrophages (MDMs) in patients with
      chronic obstructive pulmonary disease (COPD). METHODS: From January 2012 to March
      2013, peripheral blood monocytes were isolated from 32 stable COPD patients and
      32 healthy controls at First Hospital, Lanzhou University. MDM was induced and
      cultured from monocytes in vitro. The MDMs from COPD patients and healthy
      controls were divided into 4 groups of COPD non-CSE (conventional culture), COPD
      CSE (4% CSE treatment for 6 h), healthy non-CSE (conventional culture) and
      healthy CSE (4% CSE treatment for 6 h). Flow cytometry (mean fluorescence
      intensity, MFI) and laser scanning confocal microscopy (fluorescence grey level)
      were applied to detect the ability of MDM phagocytosed fluorescein-labeled
      Escherichia coli (FITC-E.coli). Total antioxidative capacity (TAC) was measured
      by o-phenanthroline colorimetry. Malondialdehyde (MDA) was measured by
      thiobarbituric acid colorimetry and glutathione peroxidase (GSH-PX) by 5, 5'
      dithiobis-2-nitrobenzoic acid (DTNB) method. RESULTS: MFI and fluorescence grey
      level in COPD non-CSE group (20.2 +/- 2.2, 51.5 +/- 5.8) significantly decreased
      than those in healthy non-CSE group (56.9 +/- 6.7, 87.3 +/- 7.3). And in COPD CSE
      (7.6 +/- 0.7, 14.1 +/- 3.4) and healthy CSE groups (48.0 +/- 5.4, 69.7 +/- 6.0)
      decreased more than those in COPD non-CSE and healthy non-CSE groups (all P <
      0.01). The levels of TAC and GSH-PX in COPD non-CSE group ((4.1 +/- 0.5), (47.1
      +/- 4.1) U/ml) were lower than those in healthy non-CSE group ((5.1 +/- 0.6),
      (88.4 +/- 2.3) U/ml). And in COPD CSE and healthy CSE groups ((3.1 +/- 0.4),
      (26.8 +/- 6.2) U/ml) and (4.5 +/- 0.4), (72.3 +/- 5.1) U/ml) were respectively
      lower than those in COPD non-CSE and healthy non-CSE groups (all P < 0.01). The
      content of MDA in COPD non-CSE group was higher than that in healthy non-CSE
      group [(4.8 +/- 0.5) vs (2.1 +/- 0.4) umol/L)]. And in COPD CSE and healthy CSE
      groups ((7.7 +/- 0.9), (3.0 +/- 0.6)umol/L) were higher than those in COPD non
      CSE and healthy non-CSE groups (all P < 0.01). At basic status, positive
      correlations existed between MFI and TAC, GSH-PX (r = 0.523, 0.818, P = 0.038,
      0.001) while negative correlations between MFI and MDA (r = -0.501, P = 0.048) in
      COPD patients and after CSE treatment, the above relationships still existed (r =
      0.704, 0.716, -0.522, P = 0.002, 0.002, 0.038). CONCLUSIONS: Cigarette smoke can
      reduce the phagocytosizing ability of MDM in COPD patients. And it may be related
      with oxidative stress.

PMID- 24854908
TI  - [Expression and significance of c-Jun activation domain binding protein 1 in
      human colorectal carcinoma].
AB  - OBJECTIVE: To explore the association of Jab1 (c-Jun activation domain binding
      protein 1) expression during carcinogenesis and clinicopathological
      characteristics of colorectal carcinoma (CRC) . METHODS: Tissue specimens were
      obtained from 80 cases of CRC from January 2007 to December 2008. And the
      expression of Jab1 protein for each specimen was detected by immunohistochemistry
      (EnVision). Six representative paired samples of cancerous and paired adjacent
      normal tissues were collected for Western blot. The relationships between the
      expression level of Jab1 protein and the clinicopathological characteristics of
      primary CRC were retrospectively analyzed. RESULTS: A high-level expression of
      Jab1 was present in cancerous tissues but not in paired adjacent normal tissues.
      The positive expression rate of Jab1 protein was as high as 96.3% (77/80) . And
      its high expression rate was 82.5% (66/80) , low expression rate 17.5% (14/80)
      and 8.8% (7/80) in cancerous and paired adjacent normal tissues respectively (P <
      0.05) . Its expression was correlated with differentiation, invasion depth, TNM
      stage and lymph node metastasis (all P < 0.05) . Jab1 was significantly
      correlated with Ki-67 (r = 0.548, P < 0.01) and inversely with p27(kip1) (r = 
      0.461, P < 0.01). CONCLUSIONS: An over-expression of Jab1 protein might play an
      important role in the pathogenesis of CRC. Thus it may become a novel diagnostic
      marker and a therapeutic target in patients with CRC.

PMID- 24854910
TI  - [Association of abdominal fat distribution by computed tomography with body mass
      index and metabolic syndrome in Chinese elders].
AB  - OBJECTIVE: To explore the gender and age difference of abdominal fat distribution
      in Chinese older adults and examine the effects of metabolic syndrome (MS) on
      abdominal fat distribution by computed tomography (CT). METHODS: Chinese elders
      (aged >= 65 years old) undergoing abdominal CT scanning at our hospital from
      January 2009 to December 2010 were collected through retrospective analysis. A
      total of 52 healthy normal-weight subjects and gender-specific body mass index
      (BMI)-matched middle-aged adults were selected (28 males, 24 females) to compare
      the difference of abdominal fat during the same period. Visceral fat area (VFA)
      and subcutaneous fat area (SFA) were measured at the cross-sections of L4 and L5
      intervertebral space. RESULTS: A total of 390 subjects were enrolled. There were
      252 males and 138 females. Total abdominal fat (TAF) was not significantly
      different in both genders [female (323 +/- 122 cm2) vs male (303 +/- 141 cm2) , P
      = 0.146]. However, females had higher TAF than males after height correction (128
      +/- 49 vs 105 +/- 49 cm2/m2, P = 0.000). VFA and SFA were higher with higher BMI
      values across lean, normal weight, overweight and obese groups in both genders.
      VFA and SFA were not significantly different in both genders among 3 different
      age groups (>65-75, >75-85, >85 years; P > 0.05). Compared with healthy normal
      weight elders and BMI-matched middle-aged adults, VFA and SFA increased with more
      components of MS except in only one component group. When the patients were
      excluded suffering from 2 or more components of MS, VFA was not significantly
      different between normal weight elders and those with only one component of MS
      (diabetes/hyperlipidemia/hypertension). Logistic regression analysis showed VFA
      was a risk factor for elders with MS (male: OR = 1.03, 95%CI: 1.012- 1.047;
      female: OR = 1.06, 95%CI: 1.026-1.088) . However, SFA and age were not.
      CONCLUSIONS: The elder females have more TAF than the elder males while abdominal
      fat does not increase with age in elders. TAF, VFA and SFA have a highly
      positively correlation with BMI. Visceral fat, not subcutaneous fat, is a risk
      factor for elders with MS and it increases with an increment of more than 2
      components of MS.

PMID- 24854909
TI  - [Evaluations of seven different clinical staging systems for Chinese patients
      with hepatocellular carcinoma undergoing curative resection].
AB  - OBJECTIVE: To compare the performance of 7 prognostic staging systems in
      predicting the survival of surgical patients with hepatocellular carcinoma (HCC).
      METHODS: A total of 908 surgical HCC patients were recruited from January, 1999
      to December, 2010 at our hospital. They were assigned retrospectively into
      different stages according to the classification criteria of 7 different staging
      systems. That is, Tumor-Node-Metastasis classification system (TNM7th), Barcelona
      Clinic Liver Cancer staging system (BCLC), Tokyo score, Japan Integrated Staging
      score (JIS), model for the Chinese University Prognostic Index grade (CUPI),
      Cancer of the Liver Italian Program score (CLIP) and Okuda staging. Kaplan-Meier
      survival estimations were performed and P values assessed with Log-rank test.
      RESULTS: Significant survival difference was found across all groups of these
      staging systems(P < 0.05) except for comparison between TNM7th Stage IV versus
      III (P = 0.538), Tokyo score 4 versus 3 (P = 0.290) and 1 versus 0(P = 0.398),
      CLIP score 4 versus 3 (P = 0.073) and 3 versus 2 (P = 0.805) and Okuda stage II
      versus stage I (P = 0.872). For neutralizing potential bias in comparing
      prognostic scores with different numbers of stages, Akaike information criterion
      (AIC) was calculated by the results of Cox's regression. Therefore TNM7th had the
      lowest AIC result (AIC = 3 719.39). CONCLUSION: TNM7th staging system is a better
      staging model for HCC of Chinese population among seven currently applied staging
      systems.

PMID- 24854911
TI  - [Relationship between metabolic diseases and all-cause and cardiovascular death
      in an elderly male population during a 15-year follow-up].
AB  - OBJECTIVE: To explore the relationship between metabolic diseases and death from
      all causes, cardiovascular diseases (CVD) in an elderly male population. METHODS:
      A cohort of 1 447 elderly males was followed up for 15 years from 1996 to 2011.
      All of them received annual check-ups at our hospital. The Cox proportional
      hazard model was applied to multivariate survival analysis for all-cause and CVD
      mortality. And the cumulative survival rates were calculated by Kaplan-Meier
      method and log-rank test was used to compare the survival rates. RESULTS: During
      a 15-year follow-up, 639 subjects died, including 186 deaths from cardiovascular
      causes. Multivariate Cox regression analysis showed that age [relative risk (RR)
      = 1.131, 95% confidence interval (CI) 1.114-1.148], impaired glucose metabolism
      (RR = 1.344, 95% CI 1.139-1.585), hypertension (RR = 1.241, 95% CI 1.055-1.460) ,
      elevated fasting glucose level (RR = 1.101, 95% CI 1.031-1.177) and lower body
      mass index (BMI) (RR = 0.968, 95% CI 0.943-0.993) increased the risks of all
      cause mortality while age (RR = 1.119, 95% CI 1.086-1.153) , impaired glucose
      metabolism (RR = 1.856, 95% CI 1.386-2.458) and hypertension (RR = 1.699, 95% CI
      1.242-2.324) elevated the risks of CVD mortality. The cumulative survival rates
      from all-cause and CVD mortality in impaired glucose regulation and diabetes
      group were significantly lower than those in normal glucose tolerance group (P <
      0.01) . However, no difference existed between impaired glucose regulation (IGR)
      and diabetes groups. The cumulative survival rates from all-cause and CVD
      mortality significantly decreased in cases of impaired glucose metabolism and
      hypertension (P < 0.01) . The cumulative survival rates from all-cause mortality
      in low BMI group were significantly lower than those in normal and high BMI
      groups (P < 0.05) . A substantially higher risk of all-cause and CVD mortality
      was present in those with 2 or more metabolic disorders versus those with 0-1
      metabolic disorder (P < 0.01). CONCLUSIONS: Malignant tumor and CVD are the main
      cause of death for Chinese elderly male population. Advanced age, impaired
      glucose metabolism, hypertension and 2 or more concurrent metabolic disorders are
      risk factors of all-cause and CVD mortality. And underweight is associated with
      an increased risk of death in elders.

PMID- 24854912
TI  - [Detection of serum Chlamydia pneumoniae antibodies and analysis of epidemiologic
      data in 5 years].
AB  - OBJECTIVE: To detect serum Chlamydia pneumoniae (C.pneumonia) antibodies and
      analyze the epidemiologic data. METHODS: Micro-immunofluorescence (MIF) was used
      to detect IgG and IgM antibodies against C.pneumoniae in 7 802 serum specimens
      from May 2008 to September 2013. C.pneumoniae past or recent infections were
      determined based on specific IgG and IgM antibodies and their titers. The
      analysis of relationship between age, gender and other clinical factors
      associated with antibody titers was performed. RESULTS: The positive rate of
      C.pneumonia IgG antibodies ( >= 1: 16 and <1: 512) was 87.5% (6 827/7 802). And
      the lowest rate of 50.6% (78/154) was shown in patients of 2-4 years age group
      while the highest rate of 98.7% (1 277/1 294) in those above 70 years old. The
      average geometric mean titer (GMT) of C.pneumonia IgG antibodies was 43.9. GMT in
      males was significantly higher than that in females (45.8 vs 41.9, P = 0.000 1).
      And 282 (3.6%) patients were diagnosed with recent C.pneumoniae infection (IgG >=
      1: 512 or IgM >= 1: 16 or acute and convalescent serum antibody titers turned to
      positive or four times and more elevated). The lowest rate of 0.5% (2/417) was
      detected in < 2-year-old patients while the highest rate of 6.7% (24/357) in 10
      14-year-old group patients. The miss ratio was as high as 68.1% (192/282) if
      C.pneumoniae IgM antibody was used as an only criteria for C. pneumoniae recent
      infection. The recent infection rates in patients with autoimmune diseases (7.1%
      (24/336) ) and those with pneumonia/chest radiological shadow findings (4.7%
      (69/1 467)) were statistically higher than the average rate (3.6%) of total
      population (P = 0.000 4, 0.014 0). CONCLUSIONS: The positive rate of C.pneumonia
      IgG antibody is quite high in the population. And the GMT of C.pneumoniae IgG
      antibody in males is significantly high than that in females. Recent C.pneumonia
      infection is to be missed if IgM antibody is used as a sole criterion.

PMID- 24854913
TI  - [Clinical characteristics of adrenocorticotropic hormone independent macronodular
      adrenal hyperplasia: a report of 30 cases].
AB  - OBJECTIVE: To explore the clinical characteristics of adrenocorticotropic hormone
      (ACTH) independent macronodular adrenal hyperplasia (AIMAH). METHODS: A total of
      30 AIMAH patients from January 2001 to December 2011 at our hospital were
      reviewed retrospectively and their clinical data collected. RESULTS: AIMAH was
      equally distributed between genders. Their mean age was 44 +/- 9 years and median
      course of disease 5 years. Hypertension was the most common clinical
      manifestation. Circadian rhythm of plasma cortisol disappeared in all patients,
      and the level of 24 hour urinary free cortisol (24 hUFC) was normal only in 4
      (13.3%) patients. Both low and high dose dexamethasone suppression tests were not
      suppressed in 30 (100.0%) and 28 (93.3%) patients respectively. The stimulation
      tests for detecting aberrant expression of hormone receptors were performed in 14
      patients. At least one aberrant cortisol response was identified in 12 patients.
      Twenty-five patients underwent adrenalectomy. Among 7 patients of bilateral
      adrenalectomy, 6 achieved remission while 8 patients did so among 14 patients of
      unilateral adrenalectomy. CONCLUSIONS: AIMAH should be considered in patients
      with massively enlarged bilateral adrenal glands. Treatment modalities should be
      decided according to clinical manifestations and cortisol level so as to relieve
      symptoms and improve prognosis.

PMID- 24854914
TI  - [Detection of polA gene in whole blood samples and preliminary observations with
      molecular subtyping of Treponema pallidum].
AB  - OBJECTIVE: To detect Treponema pallidum (T.pallidum) DNA with polymerase chain
      reaction (PCR) in whole blood samples of syphilis patients and analyze their
      features of sub-genotypes. METHODS: The clinical data of patients were collected
      from July 2012 to February 2013. And polA gene of syphilis was detected by PCR.
      The arp and tpr genes of polA gene-positive samples were analyzed by the
      established genotyping system.Statistical analyses were performed to compare
      different clinical courses and features to examine their correlations. RESULTS:
      The common treponemal gene target (polA) of 35 samples were detected in whole
      blood by PCR in 181 samples. A total of 24 cases (35.8%) were positive in 67
      patients with newly diagnosed non-latent syphilis untreated patients;26 cases of
      latent syphilis were negative;7 cases (9.7%) were positive in 72 subsequent visit
      patients;4 cases (25.0%) were positive in 16 patients with sero-resistant. There
      were 4 subtypes of 14a (n = 7), 14b (n = 10), 13c (n = 4) and 14d (n = 14). Among
      those positive samples, there were 4 sero-resistant samples of 3 subtypes 14d and
      1 subtype 14b. CONCLUSIONS: The feasibility of peripheral blood is confirmed.
      Although the positive rate of whole blood detection of T.pallidum gene is low,
      the method is both simple and reliable for patients with sero-resistant syphilis.

PMID- 24854916
TI  - [Clinical analyses of bilateral renal angiomyolipomas associated with tuberous
      sclerosis complex].
AB  - OBJECTIVE: To explore the clinical characteristics, diagnosis, treatment and
      outcomes of renal angiomyolipoma (RAML) associated with tuberous sclerosis
      complex (TSC). METHODS: The clinical data were analyzed for 10 cases of renal
      angiomyolipomas associated with tuberous sclerosis. There were 4 males and 6
      females with a mean age of 23.5 (9-44) years.Five patients were admitted for
      flank pain or hematuria.RAML was found by TSC associated imaging examinations for
      those with extra renal organ involvement. RESULTS: Bilateral multiple renal
      angiomyolipomas were all confirmed on imaging tests and consistent with clinical
      TSC. The maximal diameter of RAMLs was from 2 to 15(7.3 +/- 3.5) cm.Six patients
      of tumor hemorrhage had an average maximal diameter of 9.2 cm.Selective arterial
      embolization (SAE) (n = 4) and homeostasis, anti inflammation and immobilization
      therapy (n = 2) were performed.Four asymptomatic cases accepted close
      observation. During a follow-up period of 9-116 months, one of 4 SAE cases
      underwent secondary SAE due to rebleeding 12 months later while there was no
      recurrence of flank pain in other 3 cases. The mean enlargement of maximal
      diameter was 1.5 cm/year and serum creatinine elevated by 3.1 umol/L/year.Six
      cases on conservative medical therapy or under observation had a mean enlargement
      of maximal diameter of 0.7 cm/year and serum creatinine elevated by 2.2
      umol/L/year. Three cases remained asymptomatic, one died of respiratory failure
      from TSC-associated pulmonary lymphangioleiomyomatosis, two had flank pain at 16
      and 40 months respectively, one underwent secondary SAE and another received
      rapamycin with marked tumor regression. CONCLUSIONS: Bilateral multiple RAMLs
      occur in most TSC patients. After excluding malignancy, SAE becomes an important
      choice for its mini-invasiveness, efficacy and chances of re-embolization. And
      rapamycin provides ameliorative treatment for TSC patients.

PMID- 24854915
TI  - [Mid-long-term follow-up of radical cystectomy with orthotopic ileal neobladder
      in women patients with bladder carcinoma].
AB  - OBJECTIVE: To assess the mid-long-term efficacies of orthotopic urinary diversion
      in women. METHODS: From February 2003 to August 2012, 28 female patients with
      bladder cancer underwent radical cystectomy and orthotopic ileal neobladder.Open
      (n = 18) and laparoscopic (n = 9) procedures were performed.Ileal neobladder
      included 17 T-pouch and 11 modified Studer pouch reconstruction. The continence
      status, urodynamics, serum electrolyte and renal function were followed up.
      RESULTS: The mean follow-up period was 55 (8-114) months.Excellent continence was
      achieved during day-time in 82.1%, 92.3% and 90.5% cases at 6, 12 and 24 months
      postoperatively and in 53.6%, 88.5% and 90.5% cases at night respectively. The
      mean capacity of pouch was 282 +/- 87, 345 +/- 72 and 357 +/- 75 ml at 6, 12 and
      24 months postoperatively respectively. The mean filling pressure of pouch was
      10.8 +/- 3.2, 6.7 +/- 2.6 and 6.2 +/- 2.1 cmH2O postoperatively respectively.One
      case of neobladder-vaginal fistula was cured by surgical repair. Another case of
      urethral stenosis responded well after regular dilation for 6 months.Renal
      function and electrolyte metabolism were stable in all cases. There was no
      instance of tumor recurrence or metastasis. CONCLUSION: Orthotopic urinary
      diversion in females has excellent long-term results with fewer complications so
      that it is highly recommended.

PMID- 24854917
TI  - [Effects of intravenous immunoglobulin upon the overexpression and over
      activation of nuclear factor-kappaB and matrix metalloproteinase-9 in murine
      model of Kawasaki disease].
AB  - OBJECTIVE: To explore the changes of expression and biological activity of
      nuclear factor-kappa B (NF-kappaB) and matrix metalloproteinase-9 (MMP-9) after
      using intravenous immunoglobulin (IVIG) in a murine model of Kawasaki disease
      (KD) and elucidate the therapeutic mechanism of IVIG for the treatment of KD.
      METHODS: A total of 72 mice were categorized randomly into IVIG, KD and control
      groups.Lactobacillus casei cell wall extract (LCWE) was prepared and injected
      intraperitoneally into C57BL/6 mice to induce KD (0.5 mg single injection).IVIG
      group received an intraperitoneal injection of IVIG (2 mg/g) while KD model group
      had an intraperitoneal injection of normal saline. At Days 14, 28 and 56, the
      diameter of coronary artery was by echocardiography in 8 mice of each group. At
      the same time, the stains of hematoxylin & eosin and elastic fiber were used to
      observe the pathological damage of coronary artery. Western blot was used to
      evaluate the expressions of NF-kappaB and MMP-9, electrophoretic mobility shift
      assay (EMSA) was used to measure the activity of NF-kappaB and Gelatin zymography
      was used to evaluate the activity of MMP-9 in heart samples of murine model of
      KD. RESULTS: The local inflammatory infiltrate, composed predominantly of
      mononuclear lymphocytes, of coronary artery trunk and branches was observed at
      Days 14 and 28 while broken elastin was observed at Day 56. And the inflammatory
      cell infiltrate was less severe and no apparent broken elastin was observed in
      IVIG and control groups. On echocardiography, the average value of diameter of
      left coronary artery in KD model group was higher than that in IVIG and control
      groups (28 d:(0.48 +/- 0.07) vs (0.41 +/- 0.03) and (0.35 +/- 0.02) mm, all P <
      0.01). Compared with the other two groups, the result of Western blot showed that
      the expressions of NF-kappaB and MMP-9 in KD model group were markedly higher
      than those in IVIG treatment group and that in control group at each time point
      (28 d: (58 +/- 14) vs (25 +/- 14) & (19 +/- 11) ug/L, (100 +/- 41) vs (39 +/- 19)
      & (35 +/- 19) ug/L, all P < 0.01). The activity of NF-kappaB by EMSA and the
      result from KD model group were much higher than those from the control and IVIG
      groups (28 d: (84 788 +/- 2 081) vs (27 220 +/- 4 990) & (50 192 +/- 1 586) ug/L,
      all P < 0.01]. And it was in accord with the expression of NF-kappaB. The outcome
      of gelatin zymography demonstrated that the activity of MMP-9 had similar change
      with the expression of MMP-9(18 560 +/- 7 963) vs (9 112 +/- 3 398) & (11 834 +/-
      4 996) ug/L, all P < 0.05). CONCLUSIONS: NF-kappaB/MMP-9 is overexpressed and
      over-activated in the heart of KD mouse models. IVIG may inhibit the inflammatory
      cell infiltration and alleviate coronary artery. And such a therapeutic effect is
      possibly achieved by a suppression of the overexpression and over-activation of
      NF-kappaB/MMP-9 pathway.

PMID- 24854918
TI  - [Role of calcium-sensing receptor in hypoxia-induced airway mucous
      hypersecretion].
AB  - OBJECTIVE: To explore the mechanism of calcium-sensing receptor (CaSR) in hypoxia
      induced airway mucous hypersecretion. METHODS: Cultured human airway epithelial
      cells HBE16 by hypoxia incubator (94%N2, 1%O2, 5%CO2, 37  degrees C). HBE16 were
      transfected with CaSR targeted small interfering RNA (CaSR-siRNA), pretreated
      with a specific activator of CaSR CaCl2 and preincubated with various inhibitors
      [Galphaq/11 protein inhibitor YM-254890, phospholipase C (PLC) inhibitor U73122,
      inositol 1, 4, 5-triphosphate receptors (IP 3R) inhibitor 2-APB and cell
      permeable intracellular calcium chelator BAPTA-AM] before hypoxia. The level of
      MUC5AC mRNA was detected by reverse transcription-polymerase chain reaction (RT
      PCR). And the relative content of CaSR protein was detected by Western blot. The
      relative content of MUC5AC protein was measured by enzyme-linked immunosorbent
      assay (ELISA). The intracellular calcium concentration ([Ca2+]i) was measured by
      laser confocal microscopy. RESULTS: The relative contents of [Ca2+]i and MUC5AC
      protein were obviously higher in hypoxic group ((154.2 +/- 11.4) nmol/L, (0.624
      +/- 0.063) ug/L) than those in control group ((67.5 +/- 2.8) nmol/L, (0.257 +/-
      0.051) ug/L) (all P < 0.01). The relative levels of CaSR protein and MUC5AC mRNA
      were significantly higher in hypoxic group (0.423 +/- 0.028, 0.736 +/- 0.045)
      than those in control group (0.185 +/- 0.036, 0.321 +/- 0.034) (all P < 0.01).
      CaCl2 enhanced the effect of hypoxia. And the results had statistical
      significances (all P < 0.01). Transfection with CaSR-siRNA significantly
      decreased the effect of hypoxia (all P < 0.01). Pretreatments with Galphaq/11
      protein inhibitor, PLC inhibitor, IP 3R inhibitor or intracellular calcium
      chelator all significantly attenuated the hypoxia-induced MUC5AC hypersecretion
      and [Ca2+]i (all P < 0.05). CONCLUSION: CaSR mediates hypoxia-induced airway
      mucous hypersecretion through a signaling pathway of Galphaq/11/PLC/inositol 1,
      4, 5-triphosphate (IP 3)/[Ca2+]i.

PMID- 24854920
TI  - Outreach in pediatric radiology.

PMID- 24854919
TI  - [Effects of lipopolysaccharide pretreatment on endotoxin tolerance of human
      umbilical cord mesenchymal stem cells].
AB  - OBJECTIVE: To explore the effects of lipopolysaccharide (LPS) pretreatment on
      endotoxin tolerance of human umbilical cord mesenchymal stem cells (hUCMSCs) and
      its possible mechanism. METHODS: hUCMSCs (1*10(4) cells/well) were exposed to 0,
      0.1, 1.0, 10.0, 20.0, 30.0, 40.0, 50.0 ug/ml LPS for 24 h respectively. And the
      cell viability of hUCMSCs was detected by 3-(4, 5-dimethylthiazol-2-yl)-2, 5
      diphenyltetrazolium bromide (MTT). 1 ug/ml and 50.0 ug/ml LPS were used as
      pretreatment and apoptosis induction concentrations respectively. Pyrrolidine
      dithiocarbamate (PDTC) (20 umol/L, pretreatment for 20 min) was used as a
      specific inhibitor of nuclear transcription factor NF-kappaB. hUCMSCs were
      randomly divided by Stata software into 7 groups: control (A), LPS induction (B),
      pretreatment + LPS induction (C), PDTC (D), PDTC+ pretreatment + LPS induction
      (E), pretreatment (F) and PDTC + pretreatment (G). The apoptosis of hUCMSCs was
      measured by Hoechst 33258 staining and flow cytometry (FCM). The expressions of
      NF-kappaB p65 and cellular FLICE-inhibitory protein (c-FLIP) were measured by
      Western blot. RESULTS: The cell viability of 0, 0.1, 1.0, 10.0, 20.0, 30.0, 40.0,
      50.0 ug/ml LPS groups were 100%, (117.0 +/- 8.8)%, (134.7 +/- 6.9)%, (105.3 +/-
      8.3)%, (99.2 +/- 8.3)%, (84.2 +/- 9.3)%, (66.4 +/- 6.6)% and (59.2 +/- 8.0)%
      respectively. In comparison with 0 ug/ml LPS group, the cell viability of 1.0
      ug/ml LPS group increased significantly (P = 0.004) while decreased in 40 and 50
      ug/ml LPS groups (P = 0.005, 0.002). Hoechst 33258 staining indicated that
      chromatin of hUCMSCs was distributed evenly in group A; the apoptotic cell in
      group B dramatically increased; and the apoptotic cell in group C significantly
      decreased in comparison with that in group B. Apoptotic rates of groups A, B, C,
      D and E were (2.8 +/- 0.8)%, (29.7 +/- 3.4)%, (17.8 +/- 3.0)%, (2.9 +/- 0.4)% and
      (23.2 +/- 2.6)% respectively. Compared with group A, apoptosis rate significantly
      increased in group B (P < 0.001). The apoptotic rate in group C significantly
      decreased than that in group B (P < 0.001) while group E was higher than group C
      (P = 0.015). The levels of NF-kappaB p65 and c-FLIP in group F (0.851 +/- 0.031,
      0.534 +/- 0.053) was higher than that in group A (0.220 +/- 0.021, 0.049 +/-
      0.009) (both P < 0.001), G (0.418 +/- 0.007, 0.299 +/- 0.061) (P < 0.001, P =
      0.007). CONCLUSIONS: LPS pretreatment can resist LPS-induced hUCMSCs apoptosis
      and enhance the ability of endotoxin tolerance. And the mechanism may be related
      with activating the NF-kappaB signaling pathway and up-regulating the expression
      of c-FLIP.

PMID- 24854921
TI  - Another international imaging society--to what end? The World Federation of
      Pediatric Imaging: one voice, a common message, a unified network.

PMID- 24854922
TI  - International pediatric radiology education: who should be trained, and how?
AB  - Education is a key component in international outreach. In light of the growing
      importance of diagnostic imaging in both developed and developing countries, we
      need to embrace the goals of standardizing training, establishing international
      standards, and promoting innovations and advances in pediatric radiology
      internationally. The World Federation of Pediatric Imaging hopes to promote this
      work through education, improving diagnostic imaging and therapy access to
      children worldwide. 

PMID- 24854923
TI  - Ethiopia: who to educate, how to educate and what to teach.

PMID- 24854924
TI  - Pediatric imaging in the developing world: Colombia.

PMID- 24854925
TI  - Zambia and Zimbabwe: opportunities for growth in pediatric radiology.

PMID- 24854926
TI  - Sharing the caring: paediatric radiology in paediatric surgery outreach.

PMID- 24854927
TI  - World Federation of Pediatric Imaging (WFPI) volunteer outreach through tele
      reading: the pilot project in South Africa.
AB  - BACKGROUND: Shortages in radiology services are estimated to affect 3.5-4.7
      billion people worldwide. Teleradiology is a potential means of alleviating this
      shortage. OBJECTIVE: This paper examines the practicality and sustainability of a
      pilot pediatric teleradiology project at the Khayelitsha District Hospital in sub
      Saharan Africa. We analyze how this World Federation of Pediatric Imaging (WFPI)
      program fares against the global challenges described in the current literature
      facing these practice types. MATERIALS AND METHODS: A teleradiology pilot was
      developed to provide coverage to the Khayelitsha District Hospital after the
      district pediatrician requested assistance in interpreting radiographs. This
      program utilized a network of WFPI volunteer pediatric radiologists, direct JPEG
      conversion of digital radiographic images, and an e-mail delivery system of
      images, referral requests and teleradiology opinion. Data were collected
      retrospectively from referral cards and JPEG images of radiographs, as well as
      from the volunteer officer database. RESULTS: A total of 555 referral cards and
      1,106 radiographs were submitted for teleradiology opinion during the course of
      this pilot program; 74.6% of requests for image interpretation were chest
      radiographs and 14.2% of those were for the evaluation of tuberculosis. There
      were 40 volunteer teleradiologists from 17 countries; all spoke English, and 14
      were bilingual (8 fluent in Spanish, 5 in Portuguese, and 1 in Italian).
      CONCLUSION: Teleradiology is a viable option to alleviate radiologist shortages
      in underserved areas, but there are many challenges to designing an adequate
      teleradiology system. The WFPI pilot teleradiology program can be considered a
      successful one.

PMID- 24854928
TI  - Medecins Sans Frontieres teleradiology history.

PMID- 24854929
TI  - Satisfactions and frustrations of a volunteer tele-reader for the World
      Federation of Pediatric Imaging.

PMID- 24854930
TI  - Regional activities of the South African Society of Paediatric Imaging.

PMID- 24854931
TI  - Radiologists join to implement pediatric imaging training, education and outreach
      in Nigeria.

PMID- 24854932
TI  - Working to grow pediatric imaging in the developing world: Children's Hospital of
      Philadelphia outreach in Ethiopia.

PMID- 24854933
TI  - Worldwide Pediatric Radiology Network (RADPED) in Brazil: growth of telemedicine
      and the global exchange of knowledge.

PMID- 24854934
TI  - Outreach in paediatric radiology: European activities.

PMID- 24854935
TI  - Regional activity of the Asian and Oceanic Society for Paediatric Radiology
      (AOSPR).

PMID- 24854936
TI  - Volume sweep imaging: open-source technology for pediatric global health
      collaboration.

PMID- 24854937
TI  - Point-of-care ultrasound: a simple protocol to improve diagnosis of childhood
      tuberculosis.

PMID- 24854938
TI  - Through the eye of the suprasternal notch: point-of-care sonography for
      tuberculous mediastinal lymphadenopathy in children.
AB  - Diagnosis of pulmonary tuberculosis (TB) remains a challenge in the pediatric
      population because of the lack of sputum production for laboratory analysis.
      Chest radiography is used in the diagnosis of pulmonary TB and the hallmark of
      diagnosis is the demonstration of hilar or mediastinal lymphadenopathy. Point-of
      care sonography of the mediastinum is an alternative to chest radiography in
      detection of tuberculous lymph nodes. In the rural district health care setting
      US is often the most commonly available imaging modality and its mobility makes
      it possible to examine patients at the point of care, reducing the need for
      patients to travel to a regional hospital to acquire a chest radiograph. We
      developed and used a simplified technique for performing mediastinal sonography
      in a pilot study of 30 children (age 0 to 13 years) with proven or suspected TB.
      We can report that the procedure was successful in demonstrating the anterior
      mediastinal anatomy and predefined zones in all 30 children. We also recorded
      lymphadenopathy in 12 children. This report describes our procedural methods and
      initial results.

PMID- 24854939
TI  - Radiologic diagnosis of chest infection in children: WHO end-point consolidation.

PMID- 24854940
TI  - Partnering to solve the problem of tuberculosis.

PMID- 24854941
TI  - World Federation of Pediatric Imaging envisions Web site as a tool to share and
      disseminate top-notch educational material to a global audience at a minimal
      cost.

PMID- 24854942
TI  - Platforms for tele-reading: history and lessons learned by the World Federation
      of Pediatric Imaging.

PMID- 24854943
TI  - Store-and-forward teleradiology in the developing world--the Collegium
      Telemedicus system.

PMID- 24854944
TI  - Digital media for distance education.

PMID- 24854945
TI  - WFPI virtual communications centre: a hive of e-mail activity.

PMID- 24854946
TI  - Teleradiology quality assurance -- lessons learnt.

PMID- 24854948
TI  - A paediatric radiology text for resource-poor settings?

PMID- 24854947
TI  - Quality-assurance interventions for Africa utilising social media.

PMID- 24854950
TI  - International outreach and trainees: how to get involved--and why it's worth the
      effort.

PMID- 24854949
TI  - Partnering with centers of excellence in high- and low-middle-income countries: a
      strategy to strengthen child health globally.

PMID- 24854952
TI  - Chest computed tomography in children undergoing extra-corporeal membrane
      oxygenation: a 9-year single-centre experience.
AB  - We retrospectively reviewed the imaging findings, indications, technique and
      clinical impact in children who had undergone chest CT while undergoing extra
      corporeal membrane oxygenation (ECMO). Radiology and ECMO databases were searched
      to identify all 19 children who had undergone chest CT (20 scans in total) while
      on ECMO at our institution between May 2003 and May 2012. We reviewed all CT
      scans for imaging findings. Chest CT is performed in a minority of children on
      ECMO (4.5% in our series). Timing of chest CT following commencement of ECMO
      varied among patient groups but generally it was performed earlier in the
      neonatal group. Clinically significant imaging findings were found in the
      majority of chest CT scans. Many scans contained several findings, with most
      cases demonstrating parenchymal or pleural abnormalities. Case examples
      illustrate the spectrum of imaging findings, including underlying pathology such
      as necrotising pneumonia and severe barotrauma, and ECMO-related complications
      such as tension haemothoraces and cannula migration. The results of chest CT led
      to a change in patient management in 16 of 19 children (84%). There were no
      adverse events related to patient transfer. An understanding of scan technique
      and awareness of potential findings is important for the radiologist to provide
      prompt and optimal image acquisition and interpretation in appropriate patients. 

PMID- 24854954
TI  - Primary vitamin D receptor target genes as biomarkers for the vitamin D3 status
      in the hematopoietic system.
AB  - Vitamin D(3) belongs to the few nutritional compounds that has, via the binding
      of its metabolite 1alpha,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) to the
      transcription factor vitamin D receptor (VDR), a direct effect on gene
      regulation. The relation of thousands of genomic VDR-binding sites to a few
      hundred primary 1,25(OH)(2)D(3) target genes is still largely unresolved. We
      studied chromatin domains containing genes for the adhesion molecules CD97 and
      LRRC8A, the glucose transporter SLC37A2 and the coactivator NRIP1. These domains
      vary significantly in size (7.3 to 956 kb) but contain each one major VDR-binding
      site. In monocytic cells these four sites are associated with open chromatin and
      occupied by VDR, while in macrophage-like cells only the sites of LRRC8A, SLC37A2
      and NRIP1 are accessible and receptor bound. The VDR site of CD97 does, in
      contrast to the three other loci, not carry any DR3-type binding sequence. CD97,
      LRRC8A, SLC37A2 and NRIP1 are early responding 1,25(OH)(2)D(3) target genes in
      monocytic cells, while in macrophage-like cells they respond less and, in part,
      delayed. In primary human peripheral blood mononuclear cells from 71 prediabetic
      subjects of a vitamin D(3) intervention study (VitDmet) CD97, LRRC8A, SLC37A2 and
      NRIP1 can be used as transcriptomic biomarkers for classifying human individuals
      for their possible benefit from vitamin D(3) supplementation. In particular,
      NRIP1 exceeds the potential of the previously identified marker CD14 by more than
      40% and seems to be a well-suited molecular marker for the vitamin D(3) status in
      the hematopoietic system.

PMID- 24854955
TI  - Cannabinoid receptor antagonists and fatty acids alter endocannabinoid system
      gene expression and COX activity.
AB  - Cyclooxygenase (COX) possesses substrate affinity for the endocannabinoids (EC)
      anandamide (AEA) and 2-arachidonylglycerol (2-AG). We hypothesized that selective
      antagonism/activation of the cannabinoid receptors will increase COX activity and
      the availability of EC as substrates will lead to higher COX activity. Since the
      relationship between EC signaling of the endocannabinoid system (ECS) and the COX
      pathway in muscle has not been investigated, we examined agonist, antagonists and
      polyunsaturated fatty acid effects on ECS genes in myoblasts. At 50% confluency,
      C2C12 myoblasts were pretreated with 5 MUM of the cannabinoid receptor (CB)2
      inverse agonist AM630 for 2 h and one with both AM630 and 1 MUM of the CB1
      antagonist NESS0327. Cell cultures pretreated with AM630 were then administered
      with 25 MUM of either arachidonic acid (20:4n6), eicosapentaenoate (EPA)
      (20:5n3), docosahexaenoate (DHA) (22:6n3), AEA or bovine serum albumin (vehicle
      control) for 24 h. Quantitative polymerase chain reaction analyses were performed
      looking at ECS and prostaglandin genes. Total COX activity and COX-1 protein were
      greater in the AM630+AEA-treated cells compared to all other cell cultures. The
      mRNA for the AEA synthesis enzyme N-acyl phosphatidylethanolamine phospholipase D
      and the 2-AG synthesis enzymes diacylglycerol lipase (DAGL)alpha and DAGLbeta
      were higher in AM630+EPA-treated cells compared to the other groups. The mRNA
      levels of CB1 and CB2 were both highest in the AM630+EPA group. The mRNA for
      interleukin-6 and tumor necrosis factor-alpha was higher with AEA but lower with
      DHA and docosahexaenoyl ethanolamide (DHEA), supporting previous findings that
      the EC AEA supports activation of the COX system. These findings suggest that COX
      activity and protein levels are influenced by the ECS, specifically by the ligand
      AEA for CB1 and by inverse agonism of CB2. 

PMID- 24854957
TI  - Bioinspired flight control.

PMID- 24854956
TI  - Osteochondral tissue regeneration through polymeric delivery of DNA encoding for
      the SOX trio and RUNX2.
AB  - Native osteochondral repair is often inadequate owing to the inherent properties
      of the tissue, and current clinical repair strategies can result in healing with
      a limited lifespan and donor site morbidity. This work investigates the use of
      polymeric gene therapy to address this problem by delivering DNA encoding for
      transcription factors complexed with the branched poly(ethylenimine)-hyaluronic
      acid (bPEI-HA) delivery vector via a porous oligo[poly(ethylene glycol) fumarate]
      hydrogel scaffold. To evaluate the potential of this approach, a bilayered
      scaffold mimicking native osteochondral tissue organization was loaded with
      DNA/bPEI-HA complexes. Next, bilayered implants either unloaded or loaded in a
      spatial fashion with bPEI-HA and DNA encoding for either Runt-related
      transcription factor 2 (RUNX2) or SRY (sex determining region Y)-box 5, 6, and 9
      (the SOX trio), to generate bone and cartilage tissues respectively, were
      fabricated and implanted in a rat osteochondral defect. At 6weeks post
      implantation, micro-computed tomography analysis and histological scoring were
      performed on the explants to evaluate the quality and quantity of tissue repair
      in each group. The incorporation of DNA encoding for RUNX2 in the bone layer of
      these scaffolds significantly increased bone growth. Additionally, a spatially
      loaded combination of RUNX2 and SOX trio DNA loading significantly improved
      healing relative to empty hydrogels or either factor alone. Finally, the results
      of this study suggest that subchondral bone formation is necessary for correct
      cartilage healing. 

PMID- 24854958
TI  - A pilot study on the effect of Lactobacillus casei Zhang on intestinal microbiota
      parameters in Chinese subjects of different age.
AB  - Ageing of the population is an imminent global problem. Lactobacillus casei Zhang
      (LcZ) was isolated from Inner Mongolian fermented milk, koumiss. LcZ possesses
      numerous probiotic properties in in vitro tests and in animal models. However, it
      has never been tested in any human trial. In the current study, the impact of
      oral consumption of LcZ on different age groups was tested. Chinese subjects,
      including 10 young, 7 middle-aged and 7 elderly volunteers (with mean age of
      24.3, 47.6 and 64.7, respectively), were recruited. Each subject took 10.6 log10
      cfu LcZ daily for a continuous period of 28 days. Several parameters, including
      the amounts of LcZ and four selected groups of bacteria, change of bacterial
      diversity, short chain fatty acids (SCFA) and total bile acids (TBA), were
      monitored in faecal samples collected from the subjects before starting, during
      and after stopping oral LcZ consumption. The consumption of LcZ exhibited
      beneficial effects to the subjects by modulating faecal microbiota in a temporal
      manner with a prolonged elevation of SCFA and reduction of TBA. The potentially
      harmful Pseudomonas and Acinetobacter genera were suppressed by the probiotic
      administration. Furthermore, a moderately divergent response was observed in the
      indigenous gut populations of Bifidobacterium and Bacteroides fragilis group in
      different age subjects. Taken together, the current study has provided proof on
      the positive effect of probiotic consumption and crucial insights into the design
      and application of probiotic-based products to users of different age segments.

PMID- 24854960
TI  - Clinical relevance of source location in frontal lobe epilepsy and prediction of
      postoperative long-term outcome.
AB  - PURPOSE: To evaluate the value of magnetoencephalography (MEG) source
      localization in localization of epileptic activities and predicting surgical
      outcome in frontal lobe epilepsies (FLE). METHODS: Forty-six patients with
      presurgical MEG evaluation and intractable FLE surgery (28 male patients) were
      analyzed retrospectively with a mean follow-up of 5 years. Dipole analysis was
      performed for MEG source imaging (MSI). The localization of dipole clusters in
      relation to the dominant hemisphere, lesions, resection cavity and functional
      cortex were analyzed. The predictive value of MSI in respect to clinical outcome
      with long-term postoperative follow up was evaluated. RESULTS: Interictal focal
      epileptic activities were found in 82.6% (38/46) patients with monofocal activity
      81.6% (31/38) and multifocal activities 18.4% (7/38). Seizure free rate was 47.9%
      at the mean follow-up of 5.0 +/- 4.0 years (median 11.5, range 2-57). Seizure
      recurrence mainly occurred in the first 1 year after surgery. In the monofocal
      epileptic activity group, 58.1% (18/31) of the patients were seizure free,
      predicitng postoperative seizure freedom better than multifocal localization 0%
      (0/7) (p=0.028). Dipole clusters were completely resected in 70.9% of monofocal
      activity patients, which had higher seizure free rates compared to partial
      resection (p=0.002). In patients with surgery in the dominant hemisphere, seizure
      control was less likely (p=0.006). CONCLUSION: MSI contributes to the clinical
      prediction of postoperative outcome in FLE patients. MSI may non-invasively
      disclose early epileptogenic lesions, pointing to a resectable lesion, and it
      then facilitates shortcut route of presurgical evaluation.

PMID- 24854959
TI  - Tocilizumab in the treatment of rheumatoid arthritis: a cost-effectiveness
      analysis in the UK.
AB  - BACKGROUND: Since receiving a positive recommendation in England, Wales and
      Scotland, tocilizumab (TCZ) is one of the options available to clinicians for the
      treatment of rheumatoid arthritis (RA) patients in the UK. OBJECTIVE: The
      objective of this study was to evaluate the cost effectiveness of adding TCZ to
      the current treatment sequence of RA patients from a UK payer's perspective over
      a patient lifetime horizon. METHODS: An individual sampling model was developed
      to synthesise all clinical and economic inputs. Two scenarios were explored
      separately: patients contraindicated to methotrexate (MTX) and those MTX
      tolerant. For each scenario, the analysis compared three strategies. The standard
      of care (SoC) strategy included a sequence of the most commonly prescribed
      biologics; the other two comparator strategies considered the addition of TCZ to
      SoC at first line and second line. Patient characteristics were representative of
      UK patients. Treatment efficacy and quality-of-life evidence were synthesised
      from clinical trials and secondary sources. An analysis of a patient registry
      informed the model parameters regarding treatment discontinuation. The safety
      profile of all treatments in a given strategy was based on a network meta
      analysis and literature review. Resource utilisation, treatment acquisition,
      administration, monitoring and adverse event treatment costs were considered. All
      costs reflect 2012 prices. Uncertainty in model parameters was explored by one
      way and probabilistic sensitivity analysis. RESULTS: In the MTX-contraindicated
      population, if TCZ was added to the SoC in first line, the estimated incremental
      cost-effectiveness ratio (ICER) was L7,300 per quality-adjusted life-year (QALY)
      gained; if added in second line, the estimated ICER was L11,400 per QALY. In the
      MTX-tolerant population, the estimated costs and QALYs of the TCZ strategy were
      similar to those of the SoC strategy. Sensitivity analysis showed that parameters
      that affect the treatment cost (such as patient weight) can have a noticeable
      impact on the overall cost-effectiveness results. The majority of the other
      sensitivity analyses resulted in modest changes to the ICER. CONCLUSION: For the
      treatment of RA in MTX-tolerant and contraindicated patients, the addition of TCZ
      to the SoC was estimated to be a cost-effective strategy.

PMID- 24854961
TI  - Pediatric status epilepticus: how common is cerebrospinal fluid pleocytosis in
      the absence of infection?
AB  - PURPOSE: To determine the rate of cerebrospinal fluid (CSF) pleocytosis among
      children presenting with status epilepticus (SE) without proven central nervous
      system infection. METHOD: We performed a retrospective cross-sectional study of
      all patients aged one month to 21 years of age who were evaluated in a single
      pediatric emergency department (ED) for SE between 1995 and 2012. We limited our
      study to those children who had a CSF culture obtained and excluded those
      children with proven viral or bacterial infection. We defined SE in a patient who
      had a single seizure or a cluster of seizures without regaining consciousness
      which lasted 30 min or longer. We defined CSF pleocytosis as a CSF white blood
      cells (WBC)>10 cells/mm(3) and a peripheral leukocytosis as WBC >= 15,000
      cells/mm(3). We compared the rate of CSF pleocytosis between children with and
      without peripheral leukocytosis using the Fisher's exact test. RESULTS: We
      identified 289 ED visits for SE, of which 178 (62%) met study inclusion criteria.
      Seven children (4%, 95% confidence interval 1.7-8.2%) had CSF pleocytosis. More
      children with peripheral leukocytosis had CSF pleocytosis: (8.6% with peripheral
      leukocytosis vs. 0.9% without leukocytosis, p=0.01). CONCLUSION: CSF pleocytosis
      is relatively uncommon among children with prolonged seizures, even in the
      presence of peripheral leukocytosis. Therefore, all children with CSF pleocytosis
      after status epilepticus need comprehensive evaluation for central nervous system
      infection.

PMID- 24854962
TI  - [Hepatitis B vaccination and multiple sclerosis: from medical uncertainty to
      compensation for victims].
AB  - Cases of multiple sclerosis appearing after a mass hepatitis B vaccination
      program can lead to claims for compensation. The legal jurisdiction under which
      such claims will be examined depends on whether the vaccination was carried out
      as part of a mandatory program (implying liability of the State or employers) or
      in application of recommendations (implying responsibility of the vaccine
      manufacturer). In the literature, there is no evidence demonstrating a
      statistically significant relationship between anti-hepatitis B vaccination and
      the onset or exacerbation of multiple sclerosis, questioning even the notion of
      compensation. The analysis of the jurisprudence shows that, in a first period,
      the scientific uncertainty of a link between vaccination and onset of multiple
      sclerosis precluded any compensation to victims. Subsequently, judicial and
      administrative courts ignored this scientific uncertainty, which enabled them to
      examine claims for compensation by adopting a presumptive reasoning based on
      specific criteria and different regulations depending on the legal jurisdiction.
      According to the French high courts (Cour de cassation and Conseil d'Etat)
      scientific causality and legal causality do not necessarily have to be
      consistent, such that medical uncertainty should not be an obstacle to
      compensation for victims.

PMID- 24854963
TI  - [Clinical course of post-stroke depression in Kinshasa].
AB  - OBJECTIVES: To describe the evolution of the clinical profile of post-stroke
      depression over a period of one year and to determine factors associated with
      changes in post-stroke depression. METHODS: Prospective cohort study with a
      follow-up of 1year including 30 consecutive eligible patients. The severity of
      depression was assessed with the patient health questionnaire (PHQ9). RESULTS:
      The mean age was 55.87+/-12.67years. Seventy percent of patients were men. The
      two assessments for neurological status, perceived health status and test results
      of attention were not statistically different. The rate of depressive symptoms
      was 26.67% in 2011 and 20% in 2012. Disability and apathy were significantly
      improved. The average for disability increased from 2.77+/-1.19 to 2.46+/-2.19
      (P=0.002). From 66.7% in 2011, the proportion of patients able to walk without
      assistance rose to 93.3% in 2012 (P=0.03). In addition, the proportion of
      patients apathetic decreased from 43.3% to 13.3% (P=0.01). Greater age, female
      sex, sleep disorders and post-stroke apathy remained associated with DPAVC
      between the two assessments, with an increase in the strength of the association
      for apathy. CONCLUSIONS: The frequency of post-stroke depression is high and
      remains stable over time. Disability is the clinical feature that evolved more
      favorably. The association with apathy, present at the beginning, of the study
      was strengthened one year later.

PMID- 24854964
TI  - Loofah-like gel network formed by the self-assembly of a 3D radially symmetrical
      organic-inorganic hybrid gelator.
AB  - We report a unique loofah-like gel network that is supported by the sectional
      type hexagonal columnar assembly of flexuous furcate fibers, which are
      constructed by plane-to-plane stacking of a novel 3D radially symmetrical gelator
      with POSS as the core and L-lysine as the arm.

PMID- 24854965
TI  - A meta-analysis of an implicit measure of personality functioning: the Mutuality
      of Autonomy Scale.
AB  - The Mutuality of Autonomy scale (MA) is a Rorschach variable designed to capture
      the degree to which individuals mentally represent self and other as mutually
      autonomous versus pathologically destructive (Urist, 1977). Discussions of the
      MA's validity found in articles and chapters usually claim good support, which we
      evaluated by a systematic review and meta-analysis of its construct validity.
      Overall, in a random effects analysis across 24 samples (N = 1,801) and 91 effect
      sizes, the MA scale was found to maintain a relationship of r =.20, 95% CI
      [.16,.25], with relevant validity criteria. We hypothesized that MA summary
      scores that aggregate more MA response-level data would maintain the strongest
      relationship with relevant validity criteria. Results supported this hypothesis
      (aggregated scoring method: r =.24, k = 57, S = 24; nonaggregated scoring
      methods: r =.15, k = 34, S = 10; p =.039, 2-tailed). Across 7 exploratory
      moderator analyses, only 1 (criterion method) produced significant results.
      Criteria derived from the Thematic Apperception Test produced smaller effects
      than clinician ratings, diagnostic differentiation, and self-attributed
      characteristics; criteria derived from observer reports produced smaller effects
      than clinician ratings and self-attributed characteristics. Implications of the
      study's findings are discussed in terms of both research and clinical work. 

PMID- 24854966
TI  - Alcohol use disorder, contexts of alcohol use, and the risk of HIV transmission
      among South African male patrons of shebeens.
AB  - BACKGROUND: Shebeens in South Africa are settings in which alcohol use and sexual
      behavior often co-occur. The prevalence of alcohol use disorder (AUD), and the
      association between AUD, situations and settings, and sexual risk behavior, in
      shebeens remains unknown. METHODS: Men (n=763; mean age=30; 98% Black African)
      were recruited from townships in Cape Town, South Africa and completed a self
      administered survey that assessed alcohol use, sexual risk behaviors, and
      situations and settings of alcohol use. The Alcohol Use Disorder and Associated
      Disabilities Interview Schedule DSV-IV Version (AUDADIS-IV) was used to identify
      the likelihood of AUD. Bivariate regression analyses assessed whether screening
      for AUD predicted sexual risk behaviors. Multivariate regression analyses
      examined whether AUD and/or situations/settings predicted risk behaviors.
      RESULTS: Nearly two-thirds of men (62%) endorsed sufficient criteria for AUD;
      25%, 17%, and 20% were classified as having a mild, moderate, or severe AUD,
      respectively. AUD was associated with HIV risk such that men with AUD reported
      more unprotected sex than men without AUD. Analyses indicated that (a) individual
      (i.e., AUD) and (b) settings (i.e., frequency of having sex with a partner in a
      shebeen, tavern, or bottle store) interacted to predict unprotected sex.
      CONCLUSIONS: The prevalence of AUD among shebeen patrons was high and was
      associated with unprotected sex. Findings suggest the need to integrate both
      individual and situational/setting factors to prevent HIV among patrons of
      shebeens.

PMID- 24854969
TI  - [The NonaSantfeliu study. Baseline assessment and ten years of follow-up].
AB  - NonaSantfeliu study: A review is presented of the studies that are part of the
      initial overall assessment and the studies performed during the 10 years of
      follow-up of a cohort of nonagenarians. It is a population-based study of 186
      subjects, 76.5% women, mean age at baseline of 93.06 years, a quarter (26%) being
      institutionalized. The mean of baseline Barthel index was 60.8, and the mean for
      the Lobo's cognitive minimental was 21. Nonagenarian males with low comorbidity
      had more successful aging criteria than women with high comorbidity quantified
      with the Charlson Index. The survival rate at 10 years follow-up was very low,
      and 95.6% of the population had died. This represented an annual mortality rate
      of 9.5%. A common denominator on assessing all different annual cuts, is that the
      most important factors associated with mortality are those related to geriatric
      assessment, such as a function, cognition, dementia, and cumulative comorbidity
      and multiple medications, compared to more traditional risk factors described in
      younger populations. 

PMID- 24854971
TI  - Obesity and metabolic syndrome in football players.

PMID- 24854970
TI  - Christmas, santa claus, sugarplums and the grinch.

PMID- 24854972
TI  - 2011 Canadian Diabetes Association, Young Scientist Award Winner, Minna Woo MD
      PhD.

PMID- 24854973
TI  - Self-reported health beliefs, lifestyle and health behaviours in community-based
      patients with diabetes and hypertension.
AB  - OBJECTIVE: This study describes self-reported health and lifestyle behaviours and
      health risk beliefs among community patients diagnosed with type 2 diabetes and
      hypertension. METHODS: Patients with both type 2 diabetes and hypertension were
      recruited from community family practices across 3 Canadian Maritime provinces.
      Patients completed a survey targeting health risk beliefs, and health and
      lifestyle behaviours. Analyses examined differences in patient beliefs by age and
      sex, as well by health and lifestyle behaviour. RESULTS: Overall, 90.8% of
      patients believed that controlling both blood pressure and blood glucose were
      important, particularly women (p<0.01), and 92.8% felt that having both
      conditions put them at high risk for cardiovascular problems. Older patients
      reported higher antihypertensive medication adherence (p<0.0001). Most (90.8%)
      believed that prescription drug use was most helpful for controlling blood
      pressure, and this belief was associated with medication adherence (p<0.0001).
      Overall, patients who believed in the benefits of a given lifestyle behaviour
      were more likely to demonstrate the behaviour. CONCLUSION: The majority of
      patients surveyed were knowledgeable about their increased risk for
      cardiovascular problems. Patient lifestyle behaviours tended to mirror their
      health beliefs. These results provide important insight into the health beliefs
      and lifestyle behaviours of patients who receive the majority of their care in
      the community.

PMID- 24854967
TI  - [Guidelines for enhanced recovery after elective colorectal surgery].
AB  - Early recovery after surgery provides patients with all means to counteract or
      minimize the deleterious effects of surgery. This concept is suitable for a
      surgical procedure (e.g., colorectal surgery) and comes in the form of a clinical
      pathway that covers three periods (pre-, intra- and postoperative). The purpose
      of this Expert panel guideline is firstly to assess the impact of each parameter
      usually included in the rehabilitation programs on 6 foreseeable consequences of
      colorectal surgery: surgical stress, postoperative ileus, water and energy
      imbalance, postoperative immobility, sleep alterations and postoperative
      complications; secondly, to validate the usefulness of each as criteria of
      efficiency criteria for success of rehabilitation programs. Two main criteria
      were selected to evaluate the impact of each parameter: the length of stay and
      frequency of postoperative complications. Lack of information in the literature
      forced experts to assess some parameters with criteria (duration of postoperative
      ileus or quality of analgesia) that mainly surrogate a positive impact for the
      implementation of an early recovery program. After literature analysis, 19
      parameters were identified as potentially interfering with at least one of the
      foreseeable consequences of colorectal surgery. GRADE(r) methodology was applied
      to determine a level of evidence and strength of recommendation. After synthesis
      of the work of experts using GRADE(r) method on 19 parameters, 35 recommendations
      were produced by the organizing committee. The recommendations were submitted and
      amended by a group of reviewers. After three rounds of Delphi quotes, strong
      agreement was obtained for 28 recommendations (80%) and weak agreement for seven
      recommendations. A consensus was reached among anesthesiologists and surgeons on
      a number of approaches that are likely not sufficiently applied for
      rehabilitation programs in colorectal surgery such as: preoperative intake of
      carbohydrates; intraoperative hemodynamic optimization; oral feeding resume
      before ha24; gum chewing after surgery; patient out of bed and walking at D1. The
      panel also clarified the value and place of such approaches such as: patient
      information; preoperative immunonutrition; laparoscopic surgery; antibiotic
      prophylaxis; prevention of hypothermia; systematic prevention of nausea and
      vomiting; morphine-sparing analgesic techniques; indications and techniques for
      bladder catheterization. The panel also confirmed the futility of approaches such
      as: bowel preparation for colon surgery; maintain of the nasogastric tube;
      surgical drainage for colonic surgery.

PMID- 24854974
TI  - Prevalence of metabolic syndrome among college football linemen.
AB  - OBJECTIVE: To determine the prevalence of metabolic syndrome among Canadian
      amateur football players. METHODS: University football players from Saskatchewan
      were invited to participate in this study. Each subject underwent screening for
      blood pressure using a BpTRU monitor, and serum cholesterol and fasting blood
      glucose using a Cholestech LDX analyzer. Waist circumference was recorded and
      body composition was measured by dual-energy x-ray absorptiometry. RESULTS were
      compared between linemen and non-linemen using independent sample t-tests for
      continuous data and chi-square for dichotomous variables. RESULTS: Out of 39
      players who consented to participate, 14% of linemen (3/21) and no non-linemen
      satisfied metabolic syndrome criteria. Compared to non-linemen, linemen had a
      higher waist circumference (108.0 vs. 82.9 cm; p<0.001), higher total body fat
      composition (26.4% vs. 11.2%; p<0.001), lower mean high-density lipoprotein
      cholesterol (0.93, vs. 1.12 mmol/L; p=0.021) and higher fasting blood glucose
      (5.22 vs. 4.77 mmol/L; p<0.001). CONCLUSION: Despite their young age and
      participation in an elite-level athletic program, many collegiate-level football
      linemen had features of metabolic syndrome. Although our study focused on a
      single team, we suspect these trends may be consistent across the country.

PMID- 24854976
TI  - Exposure to Alternative Healthcare Providers and Adherence to Guidelines among
      Patients with Diabetes.
AB  - OBJECTIVES: Diabetes is increasing in prevalence across Canada. In the
      continuously evolving primary care landscape, practitioners from varied training
      paths are claiming rights to care for patients, including those with diabetes.
      Little is known about patient exposure to complementary and alternative medicine
      (CAM) providers, or about such providers' use of guideline-based monitoring and
      treatment recommendations. The purpose of this study was to examine compliance
      with 4 recommendations (influenza vaccination, eye examination, glycated
      hemoglobin measurement and foot exam) by patients with diabetes who use CAM
      providers compared to those who exclusively use primary care physicians. METHODS:
      We analyzed data on 7209 patients with diabetes using the Canadian Community
      Health Survey. Patients with exposure to CAM providers were compared with
      individuals who were exposed to a family physician only. Multivariate logistic
      regression was conducted adjusted for age, sex, duration of diabetes,
      insulin/oral antihyperglycemic agent use and education. RESULTS: Approximately 4%
      of persons had been exposed to CAM providers in the preceding year. The odds
      ratio for receiving influenza vaccination among those exposed to a CAM provider
      was 0.94 (95% CI 0.74-1.17). The odds ratios for eye examinations in the
      preceding 24 months, and for foot examinations and glycated hemoglobin tests in
      the preceding 12 months were 1.02 (95% CI 0.69-1.48), 1.18 (0.83-1.67) and 1.09
      (95% CI 0.71-1.66), respectively. CONCLUSION: Our results did not show
      statistical significance in any of the 4 outcomes analyzed. This study supports
      others suggesting that persons using CAM providers do so to complement
      traditional medical care, rather than as an alternative to such care.

PMID- 24854975
TI  - Type 2 diabetes in vulnerable populations: community healthcare providers'
      perspectives on health service needs and policy implications.
AB  - OBJECTIVES: To identify a) ways of enhancing health services for vulnerable
      populations with type 2 diabetes, taking into account the social determinants of
      health; and b) health and social policy approaches to reducing the incidence of
      type 2 diabetes and improving its management. METHODS: Focus groups were held
      with 18 community healthcare providers at 3 community health centres in Toronto,
      Ontario. RESULTS: Community healthcare providers' perspectives were organized
      under 3 themes: a) the compounding effects of social factors on the health of
      people with diabetes; b) the need for responsive support at multiple levels; and
      c) barriers to change. Participants showed a good understanding of the impact of
      social determinants of health on patients' lives, and they had many ideas about
      prevention/ health promotion and strategies to enhance health services. They
      seemed less aware of the important role that political advocacy can play.
      CONCLUSION: Assessment of the policy environment and political advocacy through
      coalition-building with communities and other health and social sector service
      providers should become part of healthcare professionals' education and
      responsibility. Adequate income and access to proper resources would help with
      the prevention and optimal management of diabetes.

PMID- 24854977
TI  - Management of unmet needs in type 2 diabetes mellitus: the role of incretin
      agents.
AB  - The leading cause of morbidity and mortality in type 2 diabetes mellitus is
      cardiovascular disease. There is a need for type 2 diabetes therapies that act in
      concert with available agents to provide adequate glycemic control without
      causing hypoglycemia and weight gain, which are associated with increases in
      cardiovascular risk. Incretin-based agents-dipeptidyl peptidase-4 inhibitors and
      glucagon-like peptide-1 receptor agonists-are the newest class of
      antihyperglycemic therapies. Liraglutide and exenatide, glucagon-like peptide-1
      receptor agonists recently approved in Canada, have been shown to effectively
      lower blood glucose levels while also having beneficial effects on body weight
      and systolic blood pressure. The objective of this article is to review and
      discuss incretin-based agents, with a focus on their effects on blood glucose
      control, body weight and cardiovascular risk factors in patients with type 2
      diabetes. Relevant data were obtained by literature search using the EMBASE,
      MEDLINE and PubMed databases. 

PMID- 24854978
TI  - A message from the chair, clinical & scientific section: the year in review.

PMID- 24854979
TI  - A message from the chair, diabetes educator section: the year in review.

PMID- 24854980
TI  - Polymerization of ethylene through reversible addition-fragmentation chain
      transfer (RAFT).
AB  - The present paper reports the first example of a controlled radical
      polymerization of ethylene using reversible addition-fragmentation chain transfer
      (RAFT) in the presence of xanthates (Alkyl-OC(=S)S-R) as controlling agents under
      relative mild conditions (70  degrees C, <200 bars). The specific reactivity of
      the produced alkyl-type propagating radicals induces a side fragmentation
      reaction of the stabilizing O-alkyl Z group of the controlling agents. This
      fragmentation, rarely observed in RAFT, was proven by NMR analyses. In addition,
      semicrystalline copolymers of ethylene and vinyl acetate were also prepared with
      a similar level of control.

PMID- 24854981
TI  - Solid phase assay for comparing reactivation rates of neuraminidases of influenza
      wild type and resistant mutants after inhibitor removal.
AB  - The influenza virus neuraminidase inhibitors are normally slow binding
      inhibitors, but many mutations leading to resistance, also result in the loss of
      the slow binding phenotype. Mutations can also affect the rate of dissociation of
      the inhibitors from the neuraminidase, but the assays to measure this require
      large amounts of virus and are time consuming. To more fully understand the
      impacts of mutations on the binding and dissociation of the neuraminidase
      inhibitors we have developed a solid phase reactivation assay, which can use
      small amounts of crude virus sample bound to an ELISA plate. Multiple viruses can
      be assayed simultaneously against multiple inhibitors. Using this assay we have
      demonstrated differences in the relative rates of dissociation of the inhibitors
      and reactivation of enzyme activity among different influenza A and B viruses for
      zanamivir, oseltamivir and peramivir. In general oseltamivir dissociated the
      fastest, and dissociation of peramivir was much slower than both the other
      inhibitors. Viruses with H274Y, E119V and E119G mutations demonstrated faster
      dissociation of the inhibitor to which they were resistant. Dissociation of
      zanamivir and oseltamivir were faster from the D197E mutant, but not of
      peramivir. 

PMID- 24854982
TI  - The CRISPR/Cas9 system produces specific and homozygous targeted gene editing in
      rice in one generation.
AB  - The CRISPR/Cas9 system has been demonstrated to efficiently induce targeted gene
      editing in a variety of organisms including plants. Recent work showed that
      CRISPR/Cas9-induced gene mutations in Arabidopsis were mostly somatic mutations
      in the early generation, although some mutations could be stably inherited in
      later generations. However, it remains unclear whether this system will work
      similarly in crops such as rice. In this study, we tested in two rice subspecies
      11 target genes for their amenability to CRISPR/Cas9-induced editing and
      determined the patterns, specificity and heritability of the gene modifications.
      Analysis of the genotypes and frequency of edited genes in the first generation
      of transformed plants (T0) showed that the CRISPR/Cas9 system was highly
      efficient in rice, with target genes edited in nearly half of the transformed
      embryogenic cells before their first cell division. Homozygotes of edited target
      genes were readily found in T0 plants. The gene mutations were passed to the next
      generation (T1) following classic Mendelian law, without any detectable new
      mutation or reversion. Even with extensive searches including whole genome
      resequencing, we could not find any evidence of large-scale off-targeting in rice
      for any of the many targets tested in this study. By specifically sequencing the
      putative off-target sites of a large number of T0 plants, low-frequency mutations
      were found in only one off-target site where the sequence had 1-bp difference
      from the intended target. Overall, the data in this study point to the
      CRISPR/Cas9 system being a powerful tool in crop genome engineering. 

PMID- 24854983
TI  - In vitro evaluation of effects of sustained anti-TNF release from MPEG-PCL-MPEG
      and PCL microspheres on human rheumatoid arthritis synoviocytes.
AB  - Anti-tumor necrosis factor alpha (TNFalpha) drugs such as etanercept (ETN) have
      been mostly used in systemic treatment of rheumatoid arthritis. To eliminate the
      side effects in long-term treatments and to achieve a local sustained anti
      inflammatory effect, a controlled drug delivery system is needed for anti
      TNFalpha drugs. This study aims to develop novel injectable microcarriers of ETN
      that can provide long-term controlled release of this protein drug upon intra
      articular application. In this study, poly(epsilon-caprolactone) (PCL) and its
      copolymer with poly(ethylene glycol), methoxypoly(ethylene glycol)-poly(epsilon
      caprolactone)-methoxypoly(ethylene glycol) microspheres (MPEG-PCL-MPEG) were
      compared for their prospective success in rheumatoid arthritis treatment.
      Microspheres with smooth surface of a mean particle diameter of approximately 5
      MUm were prepared with both polymers. MPEG-PCL-MPEG microspheres had higher
      encapsulation efficiency than PCL microspheres. The activity of encapsulated ETN
      within MPEG-PCL-MPEG microspheres also retained while 90% of the activity of ETN
      within PCL microspheres could retain during 90-day release. MPEG-PCL-MPEG
      microspheres showed faster ETN release compared to PCL microspheres in various
      release media. Cumulative amounts of ETN released from both types of microspheres
      were significantly lower in cell culture medium and in synovial fluids than in
      phosphate buffered saline. This was mainly due to protein adsorption onto
      microspheres. Hydrophilic MPEG segment enhanced ETN release while preventing
      protein adsorption on microspheres compared to PCL. Sustained ETN release from
      microspheres resulted with a significant decrease in pro-inflammatory cytokines
      (TNFalpha, IFNgamma, IL-6, IL-17) and MMP levels (MMP-3, MMP-13), while
      conserving viability of fibroblast-like synoviocytes compared to the free drug.
      Results suggest that MPEG-PCL-MPEG is a potential copolymer of PCL that can be
      used in development of biomedical materials for effective local treatment
      purposes in chronic inflammatory arthritis owing to enhanced hydrophilicity. Yet,
      PCL microspheres are also promising systems having good compatibility to
      synoviocytes and would be especially the choice for treatment approach requiring
      longer term and slower release. 

PMID- 24854986
TI  - Why fat taxes won't make us thin.
AB  - Increasing prevalence of overweight and obesity has led policy-makers to consider
      health-related taxes to limit the consumption of unhealthy foods and beverages.
      Such taxes are currently already in place in countries in Europe (e.g. Hungary,
      France and Finland) and in various states in the USA. Although these taxes are
      possibly efficient in reducing by a small amount the consumption of targeted
      products if the tax is fully transmitted to the consumer, there is too little
      available evidence on what will be consumed instead and whether these food
      substitutions undermine the hoped-for health benefits of the tax. We also know
      very little on how the food supply side will respond and what overall impact this
      will have. Without a proper appreciation of the potential indirect impacts we do
      not know the overall impact of taxes foods on unhealthy foods and beverages and
      further that there is a very real possibility that they may not be beneficial for
      health after all. 

PMID- 24854987
TI  - Helium isotope enrichment by resonant tunneling through nanoporous graphene
      bilayers.
AB  - Graphene is impermeable to gases, but introducing subnanometer pores can allow
      for selective gas separation. Because graphene is only one atom thick, tunneling
      can play an important role, especially for low-mass gases such as helium, and
      this has been proposed as a means of separating (3)He from (4)He. In this paper,
      we consider the possibility of utilizing resonant tunneling of helium isotopes
      through nanoporous graphene bilayers. Using a model potential fit to previously
      reported DFT potential energy surfaces, we calculate the thermal rate constant as
      a function of interlayer separation using a recently described time-independent
      method for arbitrary multibarrier potentials. Resonant transmission allows for
      the total flux rate of (3)He to remain the same as the best-known single-barrier
      pores but doubles the selectivity with respect to (4)He when the optimal
      interlayer spacing of 4.6 A is used. The high flux rate and selectivity are
      robust against variations of the interlayer spacing and asymmetries in the
      potential that may occur in experiment. 

PMID- 24854984
TI  - Chitosan coating to enhance the therapeutic efficacy of calcium sulfate-based
      antibiotic therapy in the treatment of chronic osteomyelitis.
AB  - We demonstrate that coating calcium sulfate with deacetylated chitosan enhances
      the elution profile of daptomycin by prolonging the period during which high
      concentrations of antibiotic are released. Coatings reduced initial bolus release
      of daptomycin by a factor of 10 to approximately 1000 ug/ml, and levels remained
      above 100 ug/ml for up to 10 days. Chitosan-coated and uncoated calcium sulfate
      implants with and without 15% daptomycin were evaluated in an experimental model
      of staphylococcal osteomyelitis through bacteriology scores, radiology,
      histopathology, and Gram staining. Significant reduction in bacteriology scores
      was observed for implants containing daptomycin and coated with chitosan compared
      with all the other groups. We confirm that the use of chitosan-coated calcium
      sulfate beads for local antibiotic delivery can be correlated with an improved
      therapeutic outcome following surgical debridement in the treatment of chronic
      osteomyelitis. 

PMID- 24854985
TI  - Bisphosphonate release profiles from magnetite microspheres.
AB  - Hyperthermia has been suggested as a novel, minimally invasive cancer treatment
      method. After implantation of magnetic nano- or microparticles around a tumour
      through blood vessels, irradiation with alternating magnetic fields facilitates
      the efficient in situ hyperthermia even for deep-seated tumours. On the basis of
      this idea, if the microspheres are capable of delivering drugs, they could be
      promising multifunctional biomaterials effective for chemotherapy as well as
      hyperthermia. In the present study, magnetite microspheres were prepared by
      aggregation of the iron oxide colloid in water-in-oil (W/O) emulsion. The release
      behaviour of alendronate, a typical bisphosphonate, from the microspheres was
      examined in vitro as a model of the bone tumour prevention and treatment system.
      The alendronate was successfully incorporated onto the porous magnetite
      microspheres in vacuum conditions. The drug-loaded microspheres maintained their
      original spherical shapes even after shaking in ultrapure water for 3 days,
      suggesting that they have sufficient mechanical integrity for clinical use. It
      was attributed to high aggregation capability of the magnetite nanoparticles
      through van der Waals and weak magnetic attractions. The microspheres showed slow
      release of the alendronate in vitro, resulting from tight covalent or ionic
      interaction between the magnetite and the alendronate. The release rate was
      diffusion-controlled type and well controlled by the alendronate concentration in
      drug incorporation to the microspheres. 

PMID- 24854988
TI  - ETV6-FLT3 fusion gene-positive, eosinophilia-associated myeloproliferative
      neoplasm successfully treated with sorafenib and allogeneic stem cell transplant.

PMID- 24854990
TI  - Distinct iron architecture in SF3B1-mutant myelodysplastic syndrome patients is
      linked to an SLC25A37 splice variant with a retained intron.
AB  - Perturbation in iron homeostasis is a hallmark of some hematologic diseases.
      Abnormal sideroblasts with accumulation of iron in the mitochondria are named
      ring sideroblasts (RS). RS is a cardinal feature of refractory anemia with RS
      (RARS) and RARS with marked thrombocytosis (RARS/-T). Mutations in SF3B1, a
      member of the RNA splicing machinery are frequent in RARS/-T and defects of this
      gene were linked to RS formation. Here we showcase the differences in iron
      architecture of SF3B1-mutant and wild-type (WT) RARS/-T and provide new
      mechanistic insights by which SF3B1 mutations lead to differences in iron. We
      found higher iron levels in SF3B1 mutant vs WT RARS/-T by transmission electron
      microscopy/spectroscopy/flow cytometry. SF3B1 mutations led to increased iron
      without changing the valence as shown by the presence of Fe(2+) in mutant and WT.
      Reactive oxygen species and DNA damage were not increased in SF3B1-mutant
      patients. RNA-sequencing and Reverse transcriptase PCR showed higher expression
      of a specific isoform of SLC25A37 in SF3B1-mutant patients, a crucial importer of
      Fe(2+) into the mitochondria. Our studies suggest that SF3B1 mutations contribute
      to cellular iron overload in RARS/-T by deregulating SLC25A37. 

PMID- 24854992
TI  - Bone mineral density and bone turnover among young women in Chiang Mai, Thailand.
AB  - The present study was carried out to investigate the influence of lifestyle on
      bone mineral density (BMD) and bone turnover among young women in Chiang Mai,
      Thailand. A total of 177 young women affiliated with Chiang Mai University
      hospital were enrolled. Firstly, questionnaires about their lifestyle and the
      Osteoporosis Knowledge Test (OKT) were examined. The measurement of BMD was
      assessed by Quantitative Ultrasound (QUS). Secondly, based on the measurement of
      BMD, the subjects were divided into 2 groups, a Low BMD group (L group: less than
      YAM-1.0SD) and a Normal BMD group (N group: more than YAM-1.0SD). L group (n=23)
      and N group (n=23) were examined using Osteocalcine (OC), type 1 collagen cross
      linked N-telopeptide (NTx) and undercarboxylated osteocalcin (ucOC) as bone
      turnover markers, and serum Ca, 1,25-(OH)2Vitamin D, Vitamin K1 and Vitamin K2
      (MK-4) as bone turnover related factors. Based on the results, the percentage of
      Low BMD group was 23.2%. Concerning lifestyle and BMD, the BMD of the low cheese
      intake group was 99.7+/- 17.0 and the BMD of the high cheese intake one was
      110.0+/- 23.3 (p<0.05). The BMD of the fracture experience group was 82.5+/- 11.6
      and the BMD of no-fracture group was 103.3+/- 19.6 (p<0.05). These were
      significant differences in ucOC and 1,25-(OH)2Vitamin D between L and N groups
      (p<0.05). It was suggested that BMI, food and fracture experience might affect
      BMD level and suppression of bone formation might have contributed to the low BMD
      group among young women in Chiang Mai, Thailand. 

PMID- 24854993
TI  - A case of primary systemic necrotizing vasculitis presenting primarily with
      neurologic involvement.
AB  - Systemic necrotizing vasculitis (SNV) is a type of vasculitis that presents with
      necrosis, predominantly involving large, medium-sized and small arteries.
      Peripheral neuropathy is a major clinical feature of the primary and secondary
      systemic vasculitides, and is often observed during the early phases of the
      disease, causing axonal neuropathy. The prevalence of central nervous system
      (CNS) involvement ranges from 4% to 45%. Encephalopathy, focal neurological
      deficits, and seizures are the most common manifestations and usually occur late
      during the course of SNV. In this report, we describe a 61-year-old woman with
      SNV who had both CNS and peripheral nervous system vasculitic involvement. We
      also discuss the pathophysiology of nervous system involvement in patients with
      SNV. 

PMID- 24854991
TI  - The emerging roles of DOT1L in leukemia and normal development.
AB  - Methylation of lysines within histone proteins represents a posttranslational
      modification system that can have profound effects on gene expression. An
      evolutionarily conserved, but poorly understood, histone methylation mark occurs
      on lysine 79 on histone H3 (H3K79). The H3K79 methyltransferase, DOT1L, is
      involved in a number of key processes ranging from gene expression to DNA-damage
      response and cell cycle progression. Recently, DOT1L has also been implicated in
      the development of mixed lineage leukemia (MLL)-rearranged leukemia, where
      mistargeting of DOT1L causes aberrant H3K79 methylation at homeobox genes. As
      DOT1L is essential for leukemic transformation, small-molecule inhibitors of
      DOT1L function are an attractive therapeutic target for this type of leukemia.
      However, in order to develop safe treatments, it is necessary to also understand
      the biological functions of DOT1L. Here we review the various functions of DOT1L
      in normal mammalian development. Dot1L knockout is embryonic lethal in mice and
      is important for processes as diverse as proliferation of mouse embryonic stem
      cells, induced and natural reprogramming, cardiac development and chondrogenesis.
      Additionally, while an important role for DOT1L in embryonic hematopoiesis is
      clear, its role in postnatal hematopoiesis is less so. Establishing the precise
      function of DOT1L in normal adult hematopoiesis and understanding its mode of
      action will aid in our understanding of the use of DOT1L as a therapeutic target
      in MLL-rearranged leukemia.

PMID- 24854994
TI  - Relation between sleep quality and daily physical activity in hemodialysis
      outpatients.
AB  - The purpose of this study was to examine the correlations among objective sleep
      variables, sleep-wake cycle parameters, and daily physical activity in
      hemodialysis patients and controls. Twenty-four hemodialysis patients (HD group)
      were compared with a control group consisting of 24 healthy participants matched
      for age, height, and weight. Sleep variables (total sleep time [TST], sleep
      efficiency [SE], sleep latency [SL], and waking after sleep onset [WASO]), sleep
      wake cycle parameters (the sleep-wake cycle period and the peak of sleep-wake
      cycle variance), and daily physical activity (steps per day) for each participant
      were assessed by objective methods for two weeks. While there was no difference
      in TST between the two groups, the HD group showed a significantly increased SL
      (HD: 0:29+/-0:20 vs control: 0:16+/-0:13, p < 0.05) and WASO (HD: 2:21+/-1:00 vs
      control: 1:35+/-0:41, p<0.05) and decreased SE (HD: 67.1+/-13.6% vs control:
      77.5+/-9.7%, p<0.01) compared to the control group. There was no significant
      difference in sleep-wake cycle period between the HD and control groups. However,
      the peak of sleep-wake cycle variance in the HD group (0.050+/-0.028) was
      significantly lower (t = 2.49, p<0.05) than in the control group (0.068+/-0.019).
      The number of daily steps taken in the HD group (4,774+/- 2,845 steps) was also
      significantly lower than in the control group (8,696+/- 3,047). The peak of sleep
      wake cycle variance was significantly correlated with SE (r = 0.532, p<0.01), SL
      (r = -0.501, p<0.01), and WASO (r = -0.436, p<0.01), whereas the number of steps
      showed a weak correlation only with WASO (r = -0.308, p<0.05) among the objective
      sleep parameters. Our results suggest that sleep quality in HD patients may be
      more effectively improved by maintaining the regular 24-hour sleep-wake cycle
      rather than by increasing the amount of daily physical activity, indicating that
      intervention such as measures to prevent napping during hemodialysis sessions may
      prove effective in improving the quality of sleep in HD patients. 

PMID- 24854989
TI  - How to manage mantle cell lymphoma.
AB  - Mantle cell lymphoma (MCL) is no longer a hopeless disease. Considered to carry a
      uniformly dismal prognosis so far, during the last years it has been rediscovered
      as a heterogeneous clinical and biological entity. Such a complexity has been
      highlighted by molecular genetics, unraveling different pathways of cell survival
      and progression. Concurrently, the application of new therapeutic paradigms
      including rituximab, high-dose cytarabine and stem cell transplantation
      dramatically improved treatment activity and the introduction of innovative
      targeted molecules has already led to new patient perspectives. In this
      completely new and continually evolving landscape, the clinical hemato-oncologist
      might feel disoriented on what are the best current strategies to handle such a
      critical disease and the gold standard therapeutic options for MCL. Here we
      address some burning questions on how to manage MCL patients, spacing from
      prognostic issues to the dilemma of personalized treatment in different scenarios
      of the disease: how to diagnose an MCL? Which are the fundamental staging
      procedures? What are the most reliable prognosticators? Is there a place for
      watch and wait? Which are the best treatment options for younger, elderly and
      frail patients? Which patients are addressable to high-dose therapy? What is the
      role of allogeneic transplantation? What is the most appropriate approach for
      relapsing disease in different categories of patients? What novelties are going
      to be introduced in the near future? The practical algorithms here discussed
      represent an evidence-based approach derived from results of multicenter and
      randomized trials. 

PMID- 24854995
TI  - Absence of the sternocleidomastoid muscle in a patient that underwent neck
      dissection for squamous cell carcinoma of the tongue.
AB  - The congenital absence of a skeletal muscle is a rare cause of congenital
      muscular torticollis, and the condition is associated with various unusual
      anatomical structures. We describe a rare case of congenital absence of the
      sternocleidomastoid muscle associated with squamous cell carcinoma of the tongue
      in a patient who underwent neck dissection. In this case, both the external
      jugular vein and the spinal accessory nerve were absent. However, we found that
      branches of the C3 nerve extended from the cervical plexus to the trapezius
      muscle and seemed to be acting as trapezius muscle motor nerves in place of the
      accessory nerve. After the operation, the patient was able to lift and abduct his
      right arm, and his shoulder did not droop. 

PMID- 24854996
TI  - Risk factors associated with bleeding after alteplase administration for
      pulmonary embolism: a case-control study.
AB  - STUDY OBJECTIVE: To identify risk factors associated with bleeding in patients
      who received alteplase for pulmonary embolism (PE), with a specific focus on risk
      factors available to the clinician at the time thrombolytics are being
      considered. DESIGN: Case-control study. SETTING: Large academic medical center.
      PATIENTS: Sixty-two adults with PE who were administered alteplase 100 mg over a
      2-hour infusion period between January 2000 and October 2011; of these patients,
      28 experienced major bleeding (case patients), and 34 did not develop major
      bleeding (control patients). MEASUREMENTS AND MAIN RESULTS: Risk factors for
      bleeding from alteplase were compiled from the U.S. product label and the
      literature. Multivariate logistic regression analysis was used to assess for risk
      factors independently associated with bleeding. Patients with major bleeding more
      frequently had recent major surgery (odds ratio [OR] 9.00, 95% confidence
      interval [CI] 1.01-79.99, p=0.039), an international normalized ratio above 1.7
      (OR 13.20, 95% CI 1.54-113.52, p=0.008), and one or more risk factors for
      bleeding (OR 5.02, 95% CI 1.68-15.04, p=0.003). On multivariate analysis, one or
      more risk factors for bleeding (adjusted OR 5.74, 95% CI 1.78-18.55, p=0.004) and
      body weight (adjusted OR 1.18 for each 10 kg below 100 kg, 95% CI 1.01-1.37,
      p=0.035) were independently associated with major bleeding. Intensive care unit
      length of stay after alteplase administration was significantly longer in
      patients with major bleeding (median 2.2, interquartile range [IQR] 0.9-4.8) days
      versus 1.1 (IQR 0.4-1.9 days, p=0.028). CONCLUSION: Risk factors for bleeding
      that are available to clinicians at the time the decision is made to administer
      alteplase for PE are significantly associated with the occurrence of major
      bleeding; the odds of major bleeding in patients with one or more risk factors
      for bleeding were ~5 times higher than in patients without these risk factors.
      Thus clinicians should weigh these risk factors for bleeding against the
      perceived benefit of thrombolytic therapy when deciding to administer a
      thrombolytic in an individual patient with PE.

PMID- 24854997
TI  - Galectin-1 binds mucin in human trophoblast.
AB  - Mucins are multifunctional highly glycosylated proteins expressed by the female
      reproductive tract. Differential expression of MUC1 and MUC15 has been shown in
      trophoblast. This study was undertaken to establish the distribution of mucin(s)
      in cytotrophoblast cell cultures using anti-bovine submaxillary mucin (BSM) and
      to investigate the possibility of MUC1/mucin(s) being a binding partner of
      trophoblast galectin-1. MUC1 is demonstrated here using immunocytochemistry on
      isolated cytotrophoblast and the HTR-8/SVneo extravillous trophoblast cell line
      but detection of additional trophoblast mucins cannot be excluded. Western blot
      analysis showed similar bands ranging from 30 to >200 kDa with anti-BSM and the
      well-known mucin antibodies HMFG1 and B72.3. Immunocytochemistry and cell-based
      ELISA data were found to support that all of the antibodies used are reactive
      with BSM, suggesting the presence of shared epitopes between BSM and trophoblast
      mucin(s). Binding of galectin-1 to trophoblast MUC1/mucin(s) was analyzed using a
      solid-phase assay and co-immunoprecipitation. Recombinant galectin-1 binding to
      isolated trophoblast mucin in solid-phase assay was sensitive to lactose, a
      carbohydrate inhibitor of galectin binding. In whole HTR-8/SVneo lysates, ~200
      kDa mucin was detected in galectin-1 immunoprecipitates, while endogenous
      galectin-1 was present in BSM-immunoprecipitates. Furthermore, double
      fluorescence immunocytochemistry showed overlap of galectin-1 and trophoblast
      mucins at the plasma membrane of HTR-8/SVneo cells. These results suggest that
      trophoblast mucin(s) could act as binding partners of galectin-1, in a
      carbohydrate-dependent manner.

PMID- 24854998
TI  - A distant downstream enhancer directs essential expression of Tbx18 in urogenital
      tissues.
AB  - The vertebrate T-box transcription factor gene Tbx18 performs a vital role in
      development of multiple organ systems. Tbx18 insufficiency manifests as recessive
      phenotypes in the upper urinary system, cardiac venous pole, inner ear, and axial
      skeleton; homozygous null mutant animals die perinatally. Here, we report a new
      regulatory mutation of Tbx18, a reciprocal translocation breaking 78kbp
      downstream of the gene. 12Gso homozygotes present urinary and vertebral defects
      very similar to those associated with Tbx18-null mutations, but 12Gso is clearly
      not a global null allele since homozygotes survive into adulthood. We show that
      12Gso down-regulates Tbx18 expression in a manner that is both spatially- and
      temporally-specific; combined with other data, the mutation points particularly
      to the presence of an essential urogenital enhancer located near the
      translocation breakpoint site. In support of this hypothesis, we identify a
      distal enhancer element, ECR1, which is active in developing urogenital and other
      tissues; we propose that disruption of this element leads to premature loss of
      Tbx18 function in 12Gso mutant mice. These data reveal a long-range regulatory
      architecture extending far downstream of Tbx18, identify a novel and likely
      essential urogenital enhancer, and introduce a new tool for dissecting postnatal
      phenotypes associated with dysregulation of Tbx18. 

PMID- 24854999
TI  - Enhancer diversity and the control of a simple pattern of Drosophila CNS midline
      cell expression.
AB  - Transcriptional enhancers integrate information derived from transcription factor
      binding to control gene expression. One key question concerns the extent of trans
      and cis-regulatory variation in how co-expressed genes are controlled. The
      Drosophila CNS midline cells constitute a group of neurons and glia in which
      expression changes can be readily characterized during specification and
      differentiation. Using a transgenic approach, we compare the cis-regulation of
      multiple genes expressed in the Drosophila CNS midline primordium cells, and show
      that while the expression patterns may appear alike, the target genes are not
      equivalent in how these common expression patterns are achieved. Some genes
      utilize a single enhancer that promotes expression in all midline cells, while
      others utilize multiple enhancers with distinct spatial, temporal, and
      quantitative contributions. Two regulators, Single-minded and Notch, play key
      roles in controlling early midline gene expression. While Single-minded is
      expected to control expression of most, if not all, midline primordium-expressed
      genes, the role of Notch in directly controlling midline transcription is
      unknown. Midline primordium expression of the rhomboid gene is dependent on cell
      signaling by the Notch signaling pathway. Mutational analysis of a rhomboid
      enhancer reveals at least 5 distinct types of functional cis-control elements,
      including a binding site for the Notch effector, Suppressor of Hairless. The
      results suggest a model in which Notch/Suppressor of Hairless levels are
      insufficient to activate rhomboid expression by itself, but does so in
      conjunction with additional factors, some of which, including Single-minded,
      provide midline specificity to Notch activation. Similarly, a midline glial
      enhancer from the argos gene, which is dependent on EGF/Spitz signaling, is
      directly regulated by contributions from both Pointed, the EGF transcriptional
      effector, and Single-minded. In contrast, midline primordium expression of other
      genes shows a strong dependence on Single-minded and varying combinations of
      additional transcription factors. Thus, Single-minded directly regulates midline
      primordium-expressed genes, but in some cases plays a primary role in directing
      target gene midline expression, and in others provides midline specificity to
      cell signaling inputs. 

PMID- 24855000
TI  - The basal position of nuclei is one pre-requisite for asymmetric cell divisions
      in the early mouse embryo.
AB  - The early mouse embryo undertakes two types of cell division: symmetric that
      gives rise to the trophectoderm and then placenta or asymmetric that gives rise
      to inner cells that generate the embryo proper. Although cell division
      orientation is important, the mechanism regulating it has remained unclear. Here,
      we identify the relationship between the plane of cell division and the position
      of the nucleus and go towards identifying the mechanism behind it. We first find
      that as the 8-cell embryo progresses through the cell cycle, the nuclei of most -
      but not all - cells move from apical to more basal positions, in a microtubule-
      and kinesin-dependent manner. We then find that all asymmetric divisions happen
      when nuclei are located basally and, in contrast, all cells, in which nuclei
      remain apical, divide symmetrically. To understand the potential mechanism behind
      this, we determine the effects of modulating expression of Cdx2, a transcription
      factor key for trophectoderm formation and cell polarity. We find that increased
      expression of Cdx2 leads to an increase in a number of apical nuclei, whereas
      down-regulation of Cdx2 leads to more nuclei moving basally, which explains a
      previously identified relationship between Cdx2 and cell division orientation.
      Finally, we show that down-regulation of aPKC, involved in cell polarity,
      decreases the number of apical nuclei and doubles the number of asymmetric
      divisions. These results suggest a model in which the mutual interdependence of
      Cdx2 and cell polarity affects the cytoskeleton-dependent positioning of nuclei
      and, in consequence, the plane of cell division in the early mouse embryo. 

PMID- 24855002
TI  - From the guest editor: beyond symbiosis: a cancer-centric view of the microbiome.

PMID- 24855001
TI  - Hectd1 is required for development of the junctional zone of the placenta.
AB  - The placenta plays a critical role in the growth and survival of the fetus. Here
      we demonstrate that the Homologous to the E6-AP Carboxyl Terminus (HECT) domain
      E3 ubiquitin ligase, Hectd1, is essential for development of the mouse placenta.
      Hectd1 is widely expressed during placentation with enrichment in trophoblast
      giant cells (TGCs) and other trophoblast-derived cell subtypes in the junctional
      and labyrinth zones of the placenta. Disruption of Hectd1 results in mid
      gestation lethality and intrauterine growth restriction (IUGR). Variable defects
      in the gross structure of the mutant placenta are found including alterations in
      diameter, thickness and lamination. The number and nuclear size of TGCs is
      reduced. Examination of subtype specific markers reveals altered TGC development
      with decreased expression of Placental lactogen-1 and -2 (Pl1 and Pl2) and
      increased expression of Proliferin (Plf). Reduced numbers of spongiotrophoblasts
      and glycogen trophoblasts were also found at the junctional zone of the Hectd1
      mutant placenta. Finally, there was an increase in immature uterine natural
      killer (uNK) cells in the maternal decidua of the Hectd1 mutant placenta.
      Proliferation and apoptosis are differentially altered in the layers of the
      placenta with an increase in both apoptosis and proliferation in the maternal
      decidua, a decrease in proliferation and increase in apoptosis in the labyrinth
      layer and both unchanged in the junctional zone. Together these data demonstrate
      that Hectd1 is required for development of multiple cell types within the
      junctional zone of the placenta. 

PMID- 24855004
TI  - The microbiome and obesity-an established risk for certain types of cancer.
AB  - Obesity is a major modifiable risk factor for the development of numerous types
      of cancer. Although many factors contribute to obesity-driven tumorigenesis, this
      review focuses on the functioning of the gut microbiota (the microbiome) as an
      environmental risk factor for certain types of cancers, and presents possible
      biological mediators. Obesity is a well-studied condition that is associated with
      microbiotal dysbiosis, which could result in several physiologic changes that may
      contribute to the relationship between obesity and cancer risk. These include
      altered microbial metabolism, which contributes to the generation of
      procarcinogenic toxic metabolites; increased extraction of energy and nutrient
      availability leading to metabolic dysregulation that contributes to tumor growth;
      and/or the induction of subclinical inflammation initiating tumorigenesis. Thus,
      the gut microbiota may serve as a key link between obesity and cancer and,
      therefore, viable strategies to alter the microbiota may provide novel
      therapeutics to reduce obesity-associated cancer risk. 

PMID- 24855003
TI  - Diet, the gut microbiome, and epigenetics.
AB  - Increasingly, the gut microbiome is implicated in the etiology of cancer, not
      only as an infectious agent but also by altering exposure to dietary compounds
      that influence disease risk. Whereas the composition and metabolism of the gut
      microbiome is influenced by diet, the gut microbiome can also modify dietary
      exposures in ways that are beneficial or detrimental to the human host. The
      colonic bacteria metabolize macronutrients, either as specialists or in consortia
      of bacteria, in a variety of diverse metabolic pathways. Microbial metabolites of
      diet can also be epigenetic activators of gene expression that may influence
      cancer risk in humans. Epigenetics involves heritable changes in gene expression
      via post-translational and post-transcriptional modifications. Microbial
      metabolites can influence epigenetics by altering the pool of compounds used for
      modification or by directly inhibiting enzymes involved in epigenetic pathways.
      Colonic epithelium is immediately exposed to these metabolites, although some
      metabolites are also found in systemic circulation. In this review, we discuss
      the role of the gut microbiome in dietary metabolism and how microbial
      metabolites may influence gene expression linked to colon cancer risk. 

PMID- 24855005
TI  - Microbiome, inflammation, and cancer.
AB  - Inflammation has long been suspected to play a major role in the pathogenesis of
      cancer. Only recently, however, have some mechanisms of its tumor promoting
      effects become known. Microbes, both commensal and pathogenic, are critical
      regulators of the host immune system and, ultimately, of inflammation.
      Consequently, microbes have the potential power to influence tumor progression as
      well, through a wide variety of routes, including chronic activation of
      inflammation, alteration of tumor microenvironment, induction of genotoxic
      responses, and metabolism. In this review, we will provide a general overview of
      commensal microbiota, inflammation, and cancer, as well as how microbes fit into
      this emerging field. 

PMID- 24855006
TI  - Intestinal microbiome and lymphoma development.
AB  - The intestinal microbiota and gut immune system must communicate to maintain a
      balance between tolerance and activation. Our immune system protects us from
      pathogenic microbes at the same time that our bodies are host to trillions of
      microbes, symbionts, mutualists, and some that are essential to human health.
      Since there is such a close interaction between the immune system and the
      intestinal microbiota, it is not surprising that some lymphomas such as mucosal
      associated lymphoid tissue lymphoma have been shown to be caused by the presence
      of certain bacteria. Animal models have played an important role in elucidating
      the causation and establishing the mechanism of bacteria-induced mucosal
      associated lymphoid tissue lymphoma. In this review, we discuss different ways
      that animal models have been applied to investigate links between the gut
      microbiota and lymphoma and have helped to reveal the mechanisms of microbiota
      induced lymphoma. Although there is a paucity of published studies demonstrating
      the interplay between the microbiota and lymphoma development, we believe that
      the connection is real and that it can be exploited in the future to enhance our
      understanding of causation and to improve the prognosis and treatment of
      lymphoma. 

PMID- 24855007
TI  - Pancreatic cancer, inflammation, and microbiome.
AB  - Pancreatic cancer is one of the most lethal cancers worldwide. No effective
      screening methods exist, and available treatment modalities do not effectively
      treat the disease. Inflammatory conditions such as pancreatitis represent a well
      known risk factor for pancreatic cancer development. Yet only in the past 2
      decades has pancreatic cancer been recognized as an inflammation-driven cancer,
      and the precise mechanisms underlying the pathogenic role of inflammation are
      beginning to be explored in detail. A substantial amount of preclinical and
      clinical evidence suggests that bacteria are likely to influence this process by
      activating immune receptors and perpetuating cancer-associated inflammation. The
      recent explosion of investigations of the human microbiome have highlighted how
      perturbations of commensal bacterial populations can promote inflammation and
      promote disease processes, including carcinogenesis. The elucidation of the
      interplay between inflammation and microbiome in the context of pancreatic
      carcinogenesis will provide novel targets for intervention to prevent and treat
      pancreatic cancer more efficiently. Further studies toward this direction are
      urgently needed. 

PMID- 24855008
TI  - Microbiota, oral microbiome, and pancreatic cancer.
AB  - Only 30% of patients with a diagnosis of pancreatic cancer survive 1 year after
      the diagnosis. Progress in understanding the causes of pancreatic cancer has been
      made, including solidifying the associations with obesity and diabetes, and a
      proportion of cases should be preventable through lifestyle modifications.
      Unfortunately, identifying reliable biomarkers of early pancreatic cancer has
      been extremely challenging, and no effective screening modality is currently
      available for this devastating form of cancer. Recent data suggest that the
      microbiota may play a role in the disease process, but many questions remain.
      Future studies focusing on the human microbiome, both etiologically and as a
      marker of disease susceptibility, should shed light on how to better tackle
      prevention, early detection, and treatment of this highly fatal disease. 

PMID- 24855009
TI  - Microbiome in reflux disorders and esophageal adenocarcinoma.
AB  - The incidence of esophageal adenocarcinoma has increased dramatically in the
      United States and Europe since the 1970s without apparent cause. Although
      specific host factors can affect risk of disease, such a rapid increase in
      incidence must be predominantly environmental. In the stomach, infection with
      Helicobacter pylori has been linked to chronic atrophic gastritis, an
      inflammatory precursor of gastric adenocarcinoma. However, the role of H. pylori
      in the development of esophageal adenocarcinoma is not well established.
      Meanwhile, several studies have established that a complex microbiome in the
      distal esophagus might play a more direct role. Transformation of the microbiome
      in precursor states to esophageal adenocarcinoma-reflux esophagitis and Barrett
      metaplasia-from a predominance of gram-positive bacteria to mostly gram-negative
      bacteria raises the possibility that dysbiosis is contributing to pathogenesis.
      However, knowledge of the microbiome in esophageal adenocarcinoma itself is
      lacking. Microbiome studies open a new avenue to the understanding of the
      etiology and pathogenesis of reflux disorders. 

PMID- 24855011
TI  - Microbiome and colorectal carcinoma: insights from germ-free and conventional
      animal models.
AB  - The mammalian microbiota plays a crucial role in the pathogenesis of many
      diseases. Thanks to recent advances in metagenomics, proteomics, and
      metabolomics, microbiome composition and metabolic activity can now be studied in
      detail. Results obtained by such fascinating and provocative studies would be
      meaningless without considering the perspective of the whole organism. Our work
      using gnotobiology as the major tool to unravel the mechanisms of host-microbe
      interaction has demonstrated the crucial role of microbiota in the initiation and
      progression of inflammation-associated colorectal neoplasia. Carcinogenesis in
      the gut is driven by the presence of potentially harmful microbes or by lack of
      protective ones, by the production of carcinogens generated by microbes, and by
      the induction of inflammation and modulation of the immune system. Here, we
      review these mechanisms with special emphasis on those where gnotobiology has
      yielded important insights. 

PMID- 24855010
TI  - Gastric microbiome and gastric cancer.
AB  - Cancer of the stomach is the fourth most common cancer worldwide. The single
      strongest risk factor for gastric cancer is Helicobacter pylori-associated
      chronic gastric inflammation. Among persons with H. pylori infection, strain
      specific components, host immune responses, and environmental factors influence
      the risk for gastric disease, including adenocarcinoma of the stomach, although
      only a small proportion of infected persons develop the malignancy. Recent
      advances in DNA sequencing technology have uncovered a complex community of
      noncultivatable inhabitants of the human stomach. The interaction between these
      inhabitants, collectively referred to as the gastric microbiota, and H. pylori
      likely affects gastric immunobiology and possibly the sequelae of H. pylori
      infection. Thus, characterization of the gastric microbiota in subjects with and
      without H. pylori infection could provide new insight into gastric homeostasis
      and the pathogenesis of H. pylori-associated disease, including gastric cancer. 

PMID- 24855012
TI  - Gut microbiome and colorectal adenomas.
AB  - The trillions of bacteria that naturally reside in the human gut collectively
      constitute the complex system known the gut microbiome, a vital player for the
      host's homeostasis and health. However, there is mounting evidence that
      dysbiosis, a state of pathological imbalance in the gut microbiome is present in
      many disease states. In this review, we present recent insights concerning the
      gut microbiome's contribution to the development of colorectal adenomas and the
      subsequent progression to colorectal cancer (CRC). In the United States alone,
      CRC is the second leading cause of cancer deaths. As a result, there is a high
      interest in identifying risk factors for adenomas, which are intermediate
      precursors to CRC. Recent research on CRC and the microbiome suggest that
      modulation of the gut bacterial composition and structure may be useful in
      preventing adenomas and CRC. We highlight the known risk factors for colorectal
      adenomas and the potential mechanisms by which microbial dysbiosis may contribute
      to the etiology of CRC. We also underscore novel findings from recent studies on
      the gut microbiota and colorectal adenomas along with current knowledge gaps.
      Understanding the microbiome may provide promising new directions towards novel
      diagnostic tools, biomarkers, and therapeutic interventions for CRC. 

PMID- 24855013
TI  - Microbiota and immune responses in colon cancer: more to learn.
AB  - Increasing knowledge about the gut microbiota composition together with a
      resurgence in attention to the impact of the host immune system on tumor
      development triggered our interest in exploring how the interplay of the
      microbiota and the immune system represents an emerging area of interest.
      Determining how the immune system may alter gut microbiota composition, or the
      converse, and whether these interactions increase or reduce cancer risk may be
      relevant to generate more effective colon cancer preventive strategies. 

PMID- 24855014
TI  - Halomonas qiaohouensis sp. nov., isolated from salt mine soil in southwest China.
AB  - Two Gram-stain negative, moderately halophilic, aerobic, motile bacteria,
      designated strains YIM QH88(T) and YIM QH103, were isolated from the Qiaohou salt
      mine in Yunnan, southwest China. Cells of the strains were observed to be rod
      shaped and produce creamy-coloured colonies. Growth of the two strains was
      observed at 10-45  degrees C (optimum 25-37  degrees C), at pH 6.0-10.0 (optimum
      7.0-8.0), and in the presence of 0.5-20 % (w/v) NaCl (optimum 2-6 %). The two
      strains were found to contain summed feature 8 (C18:1 omega7c/omega6c), C19:0
      cyclo omega8c and C16:0 as the major cellular fatty acids. The polar lipids were
      identified as diphosphatidylglycerol, phosphatidylglycerol,
      phosphatidylethanolamine and unknown phospholipid. The G+C content of the genomic
      DNA of strains YIM QH88(T) and YIM QH103 were determined to be 64.6 and 64.2
      mol%, respectively, and the predominant respiratory quinone detected was
      ubiquinone 9. Phylogenetic analyses based on 16S rRNA gene sequences indicated
      that strains YIM QH88(T) and YIM QH103 formed a distinct lineage within the genus
      Halomonas and were most closely related to Halomonas pantelleriensis DSM 9661(T)
      with 97.3 and 97.5 % of 16S rRNA sequence similarity respectively. The DNA-DNA
      hybridization relatedness value for strains YIM QH88(T) and YIM QH103 was 95.2 +/
      0.8 %. The levels of DNA-DNA relatedness between each of these two strains and
      the type strains of phylogenetically closely related Halomonas species were
      clearly below 70 %. On the basis of their phylogenetic analysis, DNA-DNA
      hybridization relatedness, phenotypic and chemotaxonomic characteristics, strains
      YIM QH88(T) and YIM QH103 should be classified as a novel species of the genus
      Halomonas, for which the name Halomonas qiaohouensis sp. nov. is proposed. The
      type strain is YIM QH88(T) (=DSM 26770(T) =CCTCC AB 2012965(T)). 

PMID- 24855015
TI  - Retrograde intraciliary trafficking of opsin during the maintenance of cone
      shaped photoreceptor outer segments of Xenopus laevis.
AB  - Photoreceptor outer segments (OSs) are essential for our visual perception, and
      take either rod or cone forms. The cell biological basis for the formation of
      rods is well established; however, the mechanism of cone formation is ill
      characterized. While Xenopus rods are called rods, they exhibit cone-shaped OSs
      during the early process of development. To visualize the dynamic reorganization
      of disk membranes, opsin and peripherin/rds were fused to a fluorescent protein,
      Dendra2, and expressed in early developing rod photoreceptors, in which OSs are
      still cone-shaped. Dendra2 is a fluorescent protein which can be converted from
      green to red irreversibly, and thus allows spatiotemporal labeling of proteins.
      Using a photoconversion technique, we found that disk membranes are assembled at
      the base of cone-shaped OSs. After incorporation into disks, however, Opsin
      Dendra2 was also trafficked from old to new disk membranes, consistent with the
      hypothesis that retrograde trafficking of membrane components contributes to the
      larger disk membrane observed toward the base of the cone-shaped OS. Such
      retrograde trafficking is cargo-specific and was not observed for peripherin/rds
      Dendra2. The trafficking is unlikely mediated by diffusion, since the disk
      membranes have a closed configuration, as evidenced by CNGA1 labeling of the
      plasma membrane. Consistent with retrograde trafficking, the axoneme, which
      potentially mediates retrograde intraflagellar trafficking, runs through the
      entire axis of OSs. This study provides an insight into the role of membrane
      reorganization in developing photoreceptor OSs, and proves that retrograde
      trafficking of membrane cargoes can occur there.

PMID- 24855016
TI  - First trimester screening cannot predict adverse outcomes yet.
AB  - The use of first trimester screening to detect aneuploidy has become an integral
      part of prenatal care. The application of similar screening algorithms to
      identify women at the highest risk for other adverse pregnancy outcomes in the
      first trimester could potentially have a major clinical impact. There has been
      much investigation into the ability to identify patients early in pregnancy at
      high risk for adverse pregnancy outcomes who may benefit from further
      surveillance and/or intervention. For this to be the case, however, as is true of
      any useful screening test, effective interventions need to be available.
      Unfortunately, for fetal growth restriction and stillbirth, no such interventions
      exist short of delivery. For preeclampsia, low dose aspirin has been demonstrated
      to be of benefit in specific subgroups. For preterm birth, although there are
      efficacious treatments, first trimester serum markers or cervical length
      measurements do not add significantly beyond historical or demographic factors,
      in prediction of preterm birth. Given the current evidence, first trimester
      screening, via serum or ultrasound markers, does not have sufficiently high
      enough positive predictive values for the development of preeclampsia, fetal
      growth restriction, preterm birth or stillbirth. In order to develop effective
      screening algorithms for adverse pregnancy outcomes in the first trimester,
      understanding the heterogeneous phenotype of these complications and the
      underlying pathophysiology is needed.

PMID- 24855018
TI  - Gender and sexual economics: do women view sex as a female commodity?
AB  - In the study reported here, data from implicit and behavioral choice measures did
      not support sexual economics theory's (SET's) central tenet that women view
      female sexuality as a commodity. Instead, men endorsed sexual exchange more than
      women did, which supports the idea that SET is a vestige of patriarchy. Further,
      men's sexual advice, more than women's, enforced the sexual double standard
      (i.e., men encouraged men more than women to have casual sex)-a gender difference
      that was mediated by hostile sexism, but also by men's greater implicit
      investment in sexual economics. That is, men were more likely to suppress female
      sexuality because they resisted female empowerment and automatically associated
      sex with money more than women did. It appears that women are not invested in
      sexual economics, but rather, men are invested in patriarchy, even when it means
      raising the price of sexual relations. 

PMID- 24855019
TI  - Visual environment, attention allocation, and learning in young children: when
      too much of a good thing may be bad.
AB  - A large body of evidence supports the importance of focused attention for
      encoding and task performance. Yet young children with immature regulation of
      focused attention are often placed in elementary-school classrooms containing
      many displays that are not relevant to ongoing instruction. We investigated
      whether such displays can affect children's ability to maintain focused attention
      during instruction and to learn the lesson content. We placed kindergarten
      children in a laboratory classroom for six introductory science lessons, and we
      experimentally manipulated the visual environment in the classroom. Children were
      more distracted by the visual environment, spent more time off task, and
      demonstrated smaller learning gains when the walls were highly decorated than
      when the decorations were removed. 

PMID- 24855017
TI  - Synergistic effects of leflunomide and benazepril in streptozotocin-induced
      diabetic nephropathy.
AB  - BACKGROUND: Leflunomide (LEF) and benazepril have renoprotective effects on
      diabetic nephropathy (DN) through their anti-inflammatory and anti-fibrotic
      activities. This study investigated whether combined treatment using LEF and
      benazepril affords superior protection compared with the respective
      monotherapies. METHODS: Diabetes was induced with streptozotocin (STZ, 65 mg/kg)
      by intraperitoneal injection in male Wistar rats. Two weeks after STZ injection,
      diabetic rats were treated daily for 12 weeks with LEF (10 mg/kg), benazepril (10
      mg/kg), or a combination of both. Basic parameters (body weight, fasting blood
      glucose level, and 24 h urinary protein excretion), histopathology, inflammatory
      [inflammatory cell infiltration (ED-1), monocyte chemoattractant protein-1 (MCP
      1), and Toll-like receptor-2 (TLR-2)] and glomerulosclerotic factors
      [transforming growth factor-beta1 (TGF-beta1) and connective tissue growth factor
      (CTGF)], and oxidative stress (8-hydroxy-2'-deoxyguanosine, 8-OHdG) were studied.
      RESULTS: Benazepril or LEF treatment significantly prevented body weight loss and
      24 h urinary protein excretion induced by diabetes; combined treatment with LEF
      and benazepril further improved these parameters compared with giving each drug
      alone (all p < 0.01). Increased expression of inflammatory (MCP-1 and TLR-2) and
      glomerulosclerotic (TGF-beta1 and CTGF) factors in diabetic rat kidney was
      reduced by treatment with either LEF or benazepril and was further reduced by the
      combined administration of the two drugs (p < 0.01). These effects were
      accompanied by suppression of urinary 8-OHdG excretion. There was no significant
      between-group difference in blood glucose level. CONCLUSIONS: LEF treatment
      lessens DN, and combined treatment with LEF and benazepril provides synergistic
      effects in preventing DN.

PMID- 24855020
TI  - Conformity to the opinions of other people lasts for no more than 3 days.
AB  - When people are faced with opinions different from their own, they often revise
      their own opinions to match those held by other people. This is known as the
      social-conformity effect. Although the immediate impact of social influence on
      people's decision making is well established, it is unclear whether this reflects
      a transient capitulation to public opinion or a more enduring change in privately
      held views. In an experiment using a facial-attractiveness rating task, we asked
      participants to rate each face; after providing their rating, they were informed
      of the rating given by a peer group. They then rerated the same faces after 1, 3,
      or 7 days or 3 months. Results show that individuals' initial judgments are
      altered by the differing opinions of other people for no more than 3 days. Our
      findings suggest that because the social-conformity effect lasts several days, it
      reflects a short-term change in privately held views rather than a transient
      public compliance. 

PMID- 24855021
TI  - Anterior cornual motoneuron regression pattern after sacral plexus avulsion in
      rats.
AB  - BACKGROUND: Sacral plexus avulsions lead to severe disability in patients and
      remain a thorny clinical problem due to the lack of anatomical, experimental and
      clinical studies. Attempts have been made to treat lumbosacral plexus injuries
      with such operations as direct anastomosis of the ends of injured sacral
      plexuses, and certain therapeutic effects were achieved. To further explore the
      degeneration pattern of anterior cornual motoneurons and determine the best time
      for treatment, we carried out this study. METHODS: We randomly assigned 60 SD
      rats into six groups (group A-F), with ten rats per group. The A, B, C, D, E, F
      groups included animals that received operation for L4-L6 nerve root avulsion at
      2, 4, 6, 8, 10 and 12 weeks respectively. We measured the apoptosis of motor
      neurons in the anterior corn through hematoxylin-eosin (HE) and terminal
      deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, and found
      that after sacral plexus avulsions, motor neurons in the anterior horn of the
      spinal cord gradually reduced and the apoptosis index gradually increased as the
      time went by. RESULTS: Survival rates of motoneurons at 2, 4, 6, 8, 10, and 12
      weeks after avulsion were (92.1 +/- 4.7)%, (83.6 +/- 3.7)%, (43.6 +/- 4.2)%,
      (32.1 +/- 3.5)%, (18.4 +/- 3.7)% and (12.1 +/- 3.3)%, respectively. The
      difference was most significant at week 6. CONCLUSION: Week 6 after injury is
      probably the deadline for surgical repair of sacral plexus avulsions.

PMID- 24855022
TI  - Full endoscopic endonasal expanded approach to the petroclival region: optimizing
      the carotid-clival window.
AB  - BACKGROUND: The petroclival junction (PCJ) is a challenging skull base location
      from neurosurgical point of view, especially if the retrocarotid space has to be
      reached. METHOD: In response to this challenge, this report provides a detailed
      full description of the endoscopic endonasal expanded approach (EEA) to the
      petroclival region and retrocarotid space. We present the technique step by step,
      introducing a critical concept about the optimization of the petroclival
      drilling, generating the carotid-clival window (CCW). The CCW is delimited by the
      paraclival segment of the internal carotid artery ICA anterolaterally, the
      petrous bone posterolaterally, the clival dura medially, the synchondrosis
      inferiorly, and the cavernous sinus superiorly; therefore, this approach exposes
      an important nuance to augment the previous approaches for PCJ and retrocarotid
      space. CONCLUSION: This technique provides a good surgical window and carries
      minimal risk.

PMID- 24855024
TI  - The evolution of insecticide resistance in the peach potato aphid, Myzus
      persicae.
AB  - The peach potato aphid, Myzus persicae is a globally distributed crop pest with a
      host range of over 400 species including many economically important crop plants.
      The intensive use of insecticides to control this species over many years has led
      to populations that are now resistant to several classes of insecticide. Work
      spanning over 40 years has shown that M. persicae has a remarkable ability to
      evolve mechanisms that avoid or overcome the toxic effect of insecticides with at
      least seven independent mechanisms of resistance described in this species to
      date. The array of novel resistance mechanisms, including several 'first
      examples', that have evolved in this species represents an important case study
      for the evolution of insecticide resistance and also rapid adaptive change in
      insects more generally. In this review we summarise the biochemical and molecular
      mechanisms underlying resistance in M. persicae and the insights study of this
      topic has provided on how resistance evolves, the selectivity of insecticides,
      and the link between resistance and host plant adaptation. 

PMID- 24855023
TI  - Molecular and functional characterization of Anopheles gambiae inward rectifier
      potassium (Kir1) channels: a novel role in egg production.
AB  - Inward rectifier potassium (Kir) channels play essential roles in regulating
      diverse physiological processes. Although Kir channels are encoded in mosquito
      genomes, their functions remain largely unknown. In this study, we identified the
      members of the Anopheles gambiae Kir gene family and began to investigate their
      function. Notably, we sequenced the A. gambiae Kir1 (AgKir1) gene and showed that
      it encodes all the canonical features of a Kir channel: an ion pore that is
      composed of a pore helix and a selectivity filter, two transmembrane domains that
      flank the ion pore, and the so-called G-loop. Heterologous expression of AgKir1
      in Xenopus oocytes revealed that this gene encodes a functional, barium-sensitive
      Kir channel. Quantitative RT-PCR experiments then showed that relative AgKir1
      mRNA levels are highest in the pupal stage, and that AgKir1 mRNA is enriched in
      the adult ovaries. Gene silencing of AgKir1 by RNA interference did not affect
      the survival of female mosquitoes following a blood meal, but decreased their egg
      output. These data provide evidence for a new role of Kir channels in mosquito
      fecundity, and further validates them as promising molecular targets for the
      development of a new class of mosquitocides to be used in vector control. 

PMID- 24855025
TI  - Macromolecular sensing of RNAs by exploiting conformational changes in
      supramolecular nanostructures.
AB  - Here, we report on a ratiometric fluorescence biosensor based on self-assembled
      peptide nanostructures (SPN), which can respond to conformational changes induced
      by RNA ligand binding. The design of the SPN biosensor was inspired by the
      conformational stabilization and multimerization behaviors of the HIV-1 Rev
      protein induced by cooperative protein-protein and protein-RNA interactions.
      Because conformation-sensitive SPN biosensors can orchestrate binding and signal
      transduction events, they can be developed as highly sophisticated and smart
      nanomaterials for biosensing. 

PMID- 24855026
TI  - Controlling graphene plasmons with resonant metal antennas and spatial
      conductivity patterns.
AB  - Graphene plasmons promise unique possibilities for controlling light in nanoscale
      devices and for merging optics with electronics. We developed a versatile
      platform technology based on resonant optical antennas and conductivity patterns
      for launching and control of propagating graphene plasmons, an essential step for
      the development of graphene plasmonic circuits. We launched and focused infrared
      graphene plasmons with geometrically tailored antennas and observed how they
      refracted when passing through a two-dimensional conductivity pattern, here a
      prism-shaped bilayer. To that end, we directly mapped the graphene plasmon
      wavefronts by means of an imaging method that will be useful in testing future
      design concepts for nanoscale graphene plasmonic circuits and devices. 

PMID- 24855027
TI  - Life-span extension by a metacaspase in the yeast Saccharomyces cerevisiae.
AB  - Single-cell species harbor ancestral structural homologs of caspase proteases,
      although the evolutionary benefit of such apoptosis-related proteins in
      unicellular organisms is unclear. Here, we found that the yeast metacaspase Mca1
      is recruited to the insoluble protein deposit (IPOD) and juxtanuclear quality
      control compartment (JUNQ) during aging and proteostatic stress. Elevating MCA1
      expression counteracted accumulation of unfolded proteins and aggregates and
      extended life span in a heat shock protein Hsp104 disaggregase- and proteasome
      dependent manner. Consistent with a role in protein quality control, genetic
      interaction analysis revealed that MCA1 buffers against deficiencies in the Hsp40
      chaperone YDJ1 in a caspase cysteine-dependent manner. Life-span extension and
      aggregate management by Mca1 was only partly dependent on its conserved catalytic
      cysteine, which suggests that Mca1 harbors both caspase-dependent and independent
      functions related to life-span control. 

PMID- 24855029
TI  - Strategies for the stabilization of longitudinal forward flapping flight revealed
      using a dynamically-scaled robotic fly.
AB  - The ability to regulate forward speed is an essential requirement for flying
      animals. Here, we use a dynamically-scaled robot to study how flapping insects
      adjust their wing kinematics to regulate and stabilize forward flight. The
      results suggest that the steady-state lift and thrust requirements at different
      speeds may be accomplished with quite subtle changes in hovering kinematics, and
      that these adjustments act primarily by altering the pitch moment. This finding
      is consistent with prior hypotheses regarding the relationship between body pitch
      and flight speed in fruit flies. Adjusting the mean stroke position of the wings
      is a likely mechanism for trimming the pitch moment at all speeds, whereas
      changes in the mean angle of attack may be required at higher speeds. To ensure
      stability, the flapping system requires additional pitch damping that increases
      in magnitude with flight speed. A compensatory reflex driven by fast feedback of
      pitch rate from the halteres could provide such damping, and would automatically
      exhibit gain scheduling with flight speed if pitch torque was regulated via
      changes in stroke deviation. Such a control scheme would provide an elegant
      solution for stabilization across a wide range of forward flight speeds. 

PMID- 24855030
TI  - Survey of college climates at all 28 US colleges and schools of veterinary
      medicine: preliminary findings.
AB  - In April 2011, a nationwide survey of all 28 US veterinary schools was conducted
      to determine the comfort level (college climate) of veterinary medical students
      with people from whom they are different. The original hypothesis was that some
      historically underrepresented students, especially those who may exhibit
      differences from the predominant race, ethnicity, religion, gender, or sexual
      orientation, experience a less welcoming college climate. Nearly half of all US
      students responded to the survey, allowing investigators to make conclusions from
      the resulting data at a 99% CI with an error rate of less than 2% using Fowler's
      sample-size formula. Valuable information was captured despite a few study
      limitations, such as occasional spurious data reporting and little ability to
      respond in an open-ended manner (most questions had a finite number of allowed
      responses). The data suggest that while overall the majority of the student
      population is comfortable in American colleges, some individuals who are
      underrepresented in veterinary medicine (URVM) may not feel the same level of
      acceptance or inclusivity on veterinary school campuses. Further examination of
      these data sets may explain some of the unacceptably lower retention rates of
      some of these URVM students on campuses. 

PMID- 24855031
TI  - Exploring the use of tablet PCs in veterinary medical education: opportunity or
      obstacle?
AB  - A tablet PC is a laptop computer with a touch screen and a digital pen or stylus
      that can be used for handwritten notes and drawings. The use of tablet PCs has
      been investigated in many disciplines such as engineering, mathematics, science,
      and education. The purpose of this article is to explore student and faculty
      attitudes toward and experiences with tablet PCs 6 years after the implementation
      of a tablet PC program in the College of Veterinary Medicine (CVM) at Kansas
      State University (K-State). This study reports that the use of tablet PCs has
      enhanced students' learning experiences through learner-interface interaction,
      learner-content interaction, learner-instructor interaction, and learner-learner
      interaction. This study also identifies digital distraction as the major negative
      experience with tablet PCs during class time. The tablet PC program provides CVM
      faculty the potential to pursue technology integration strategies that support
      expected learning outcomes and provides students the potential to develop self
      monitoring and self-discipline skills that support learning with digital
      technologies. 

PMID- 24855028
TI  - Number of nodules, Child-Pugh status, margin positivity, and microvascular
      invasion, but not tumor size, are prognostic factors of survival after liver
      resection for multifocal hepatocellular carcinoma.
AB  - BACKGROUND: Presently, the role of liver resection (LR) for multifocal
      hepatocellular carcinoma (HCC) remains controversial. However, in many regions
      worldwide, LR remains the only treatment modality available to such patients
      which offers the possibility of long-term cure. The aim of this study is to
      determine the outcomes and prognostic factors of patients with multifocal HCC
      after LR. METHODS: This is a retrospective analysis of 110 patients who underwent
      potentially curative LR for pathologically proven multifocal HCC between 2000 and
      2011. RESULTS: The median age was 64 (range, 18-84) years, and there were 88
      males (80.0 %). Sixty-one patients underwent a major hepatectomy, and the overall
      postoperative mortality was 1.8 %. Sixty-eight patients had liver cirrhosis, of
      which, 58 were child's A and 10 were child's B. The 1- and 5-year overall
      survival (OS) was 82 and 44 %, respectively. The corresponding 1- and 5-year
      recurrence-free survival (RFS) was 57 and 19 %, respectively. Multivariate
      analysis demonstrated that the number of nodules (>3) and presence of
      microvascular invasion were associated with RFS. Number of nodules (>3), margin
      positivity, Child-Pugh status, and presence of microvascular invasion were
      independent prognostic factors of OS. CONCLUSIONS: LR followed by treatment of
      recurrences may result in reasonable long-term survival and should be considered
      in a selected group of patients with multifocal HCC. Number of nodules (>3),
      margin positivity, Child-Pugh status, and presence of microvascular invasion, but
      not tumor size, were independent negative predictors of OS. These findings have
      potential implications on the AJCC staging for multifocal HCC.

PMID- 24855032
TI  - Low MDR1 and BAALC expression identifies a new subgroup of intermediate
      cytogenetic risk acute myeloid leukemia with a favorable outcome.
AB  - Treatment optimization in acute myeloid leukemia requires the accurate assignment
      of patients at diagnosis to specific risk groups to guide subsequent risk-adapted
      treatment stratification. In this study, we have evaluated the impact of
      expression of the gene BAALC in conjunction with MDR1 in AML with intermediate
      cytogenetic risk group to more precisely define risk assessment. Low MDR1/high
      BAALC, high MDR1/low BAALC, and high MDR1/high BAALC expressers demonstrated a
      similar clinical outcome with CR rate being 68.75-75% and relapse rate being 40
      50% and therefore could be considered as a "combined group". In contrast, low
      expression of both BAALC and MDR1 identifies an intermediate cytogenetic risk
      group a distinctly favorable outcome, with higher CR rate being 93.3%, lower
      relapse rate being 7.1%, and longer OS being 50.3% than that of the "combined
      group". Moreover, low MDR1/low BAALC expressers in the intermediate cytogenetic
      risk group also demonstrated a comparable clinical outcome with patients in the
      favorable-risk group. Thus low MDR1/low BAALC expression identifies a subgroup of
      intermediate cytogenetic risk AML patients with a remarkably good long-term
      outcome achieved by chemotherapy alone. 

PMID- 24855033
TI  - delta-Aminolevulinate dehydratase activity in lung cancer patients and its
      relationship with oxidative stress.
AB  - This study investigated the delta-aminolevulinate dehydratase (delta-ALA-D)
      activity in whole blood as well as the parameters of oxidative stress, such as
      reactive species (RS) levels in serum, thiobarbituric acid reactive substances
      (TBARS) levels, the superoxide dismutase (SOD) and catalase (CAT) activities, as
      well as total thiols (T-SH) and non-protein thiols (NPSH) levels in platelets.
      Moreover, the content of vitamin C and E in plasma and serum, respectively, in
      lung cancer patients was also investigated. We collected blood samples from
      patients (n=28) previously treated for lung cancer with chemotherapy. Patients
      were classified as stage IIIb and IV according to the Union for International
      Cancer Control (UICC). Results showed a decrease of 37% in delta-ALA-D activity
      in patients with lung cancer when compared to the control group. RS and TBARS
      levels were 8% and 99% higher in the patient group, respectively. The activity of
      SOD and CAT as well as the vitamin C content were 41%, 35% and 127% lower in
      patients when compared with controls, respectively. However, T-SH and vitamin E
      levels were 27% and 44% higher in lung cancer patients, respectively. Results
      show that the overproduction of reactive species in patients with lung cancer may
      be interfering with the activity of delta-ALA-D. Likewise, the decrease in the
      activity of this enzyme may be contributing for the oxidative stress. 

PMID- 24855034
TI  - Humanized anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles, an antibody conjugate
      with potent and selective anti-hepatocellular carcinoma activity.
AB  - Low sensitivity of tumor tissue, targeting and sustained release of the drug are
      bottlenecks of the effect of chemotherapy on hepatocellular carcinoma. In this
      study, we used the ribosome display technology to screen human anti-VEGFR 2
      single-chain antibody (ScFv) that could target directly to VEGFR2, and
      nanotechnology to prepare As2O3-nanoparticles. Then we built anti-VEGFR-2ScFv
      As2O3-stealth nanoparticles using molecular coupling technology, which
      significantly increased anti-tumor effect while reducing toxicity. The in vivo
      tissue targeting distribution and anti-tumor effects of the anti-VEGFR-2 ScFv
      As2O3-stealth nanoparticles were investigated. Our results showed that anti-VEGFR
      2 ScFv-As2O3-stealth nanoparticles could inhibit the development of liver cancer
      xenograft as a targeting agent and also significantly inhibit angiogenesis. 

PMID- 24855035
TI  - Modification of chemokine receptor expression to enhance levels of trafficking
      receptors on autologous cytokine-induced killer cells derived from patients with
      colorectal cancer.
AB  - Cytokine-induced killer (CIK) cells have achieved therapeutic benefit in
      treatment of solid tumors in clinic. However, some patients show no response
      after CIK treatment. Animal assays have shown that successful infiltration of CIK
      cells to the tumor sites could affect the outcome. Chemokines play important
      roles in lymphocyte trafficking. Understanding the molecular mechanism of
      chemokines in the process of CIK cell homing is important for further
      modification of CIK therapy. In this study, we investigated the spectrum of
      chemokine ligands in the colorectal cancer sites and observed that chemokine
      ligands CCL20 and CXCL10 were overexpressed in the CRC tumor tissues compared
      with adjacent tissues. Although the corresponding receptors CCR6 and CXCR3
      increased on CIK cells compared with PBMCs, their expression on CIK cells derived
      from CRC patients had lower levels than healthy donors, which might be a limited
      factor for autologous-CIK cells trafficking to tumor site. Importantly,
      stimulation with chemokines CCL20 and CXCL10 promotes the expression levels of
      CCR6 and CXCR3 on CIK cells, thus augmenting the relative migration of CIK cells
      in vitro. Our results suggest that modification of surface chemokine receptors
      may enhance the homing ability of CIK cells for better therapeutic achievements. 

PMID- 24855036
TI  - A pharmacogenetic survey of androgen receptor (CAG)n and (GGN)n polymorphisms in
      patients experiencing long term side effects after finasteride discontinuation.
AB  - Finasteride is a steroid 5-alpha-reductase inhibitor, approved for the treatment
      of androgenetic alopecia (AGA) and benign prostate hyperplasia. In some patients
      the treatment is associated with adverse side effects that could become
      persistent after therapy discontinuation, resulting in the so-called post
      finasteride syndrome (PFS). A pharmacogenetic component in the response to
      finasteride treatment was previously demonstrated. Two polymorphisms (CAG)
      rs4045402 and (GGN) rs3138869 in the gene encoding for the androgen receptor (AR)
      have been hypothesized to play a role in finasteride sensitivity. We aimed to
      compare the rs4045402 and rs3138869 polymorphisms prevalence in a group of 69
      selected subjects (AGA+PFS) that used finasteride to treat alopecia and developed
      persistent side effects, with that in a group of 91 untreated subjects with AGA
      (AGA), and a group of 76 untreated subjects without AGA (NO-AGA). The rs4045402
      and rs3138869 polymorphisms extreme-lengths alleles were more frequent among
      AGA+PFS (odds ratio, 5.88; 95% CI, 1.87-18.52) and AGA subjects (odds ratio,
      3.55; 95% CI, 1.13-11.21) than among NO-AGA subjects, probably reflecting the
      genetic predisposing factors for AGA development. In conclusion, we described a
      predictive effect of the less common repeats' length CAG-rs4045402 and GGN
      rs3138869 on AGA development. Prospective trials are required to confirm our
      findings also in other ethnicities, and to highlight possible further
      pharmacogenetic predictive markers of susceptibility to adverse effects. 

PMID- 24855037
TI  - How to improve the performances of Fecal Immunological Tests (FIT): Need for
      standardization of the sampling and pre-analytical phases and revision of the
      procedures for comparison of methods.
AB  - Lack of reference materials and standard procedures, on faecal tests leads to
      major problems in harmonisation of methods and do not allow the comparison of
      outcome data. In particular the absence of standardisation of pre-analytical
      characteristic was noted for faecal test methods for haemoglobin since different
      manufacturers have developed different sampling procedures and report units.
      Moreover the physical characteristics of the faecal specimen and the designs of
      specimen collection devices do not allow analysis of samples on different systems
      in consequence, faecal tests cannot be compared using standard evaluation
      protocols. To improve the harmonization of results generated using different
      analytical systems and the overall performances of test on faecal materials we
      propose the introduction of standard procedures for sampling and pre-analytical
      phase and the adoption of specific procedures based on the use of artificial
      biological samples for comparison of methods. Harmonization of sampling devices
      with the use of a standard design for pickers and a standard ratio between
      analyte and buffer for different manufacturers represent a mandatory step in the
      roadmap for harmonization of clinical laboratory measurement on faecal materials
      and can allow a significant standardisation of results generated by different
      devices.The creation of specific protocols for the evaluation and comparison of
      analytical methods for analyse of faeces could lead to a significant improvement
      in the performance of methods and systems.

PMID- 24855039
TI  - Juvenile manifestation of ultrasound communication deficits in the neuroligin-4
      null mutant mouse model of autism.
AB  - Neuroligin-4 (Nlgn4) is a member of the neuroligin family of postsynaptic cell
      adhesion molecules. Loss-of-function mutations of NLGN4 are among the most
      frequent, known genetic causes of heritable autism. Adult Nlgn4 null mutant
      (Nlgn4(-/-)) mice are a construct valid model of human autism, with both genders
      displaying a remarkable autistic phenotype, including deficits in social
      interaction and communication as well as restricted and repetitive behaviors. In
      contrast to adults, autism-related abnormalities in neonatal and juvenile Nlgn4(
      /-) mice have not been reported yet. The present study has been designed to
      systematically investigate in male and female Nlgn4(-/-) pups versus wildtype
      littermates (WT, Nlgn4(+/+)) developmental milestones and stimulus-induced
      ultrasound vocalization (USV). Neonatal development, followed daily from
      postnatal days (PND) 4 to 21, including physical development, neurological
      reflexes and neuromotor coordination, did not yield any differences between
      Nlgn4(-/-) and their WT littermates. USV in pups (PND8-9) in response to brief
      separation from their mothers revealed remarkable gender effects, and a genotype
      influence in females regarding latency to first call. In juveniles (PND22-23),
      USV monitoring upon exposure to an anesthetized female intruder mouse uncovered a
      clear genotype effect with reduced USV in Nlgn4(-/-) mice, and again a more
      prominent phenotype in females. Together, these data support an early
      manifestation of communication deficits in Nlgn4(-/-) mice that appear more
      pronounced in immature females with their overall stronger USV as compared to
      males. 

PMID- 24855040
TI  - Mechanistic study of the role of primary amines in precursor conversions to
      semiconductor nanocrystals at low temperature.
AB  - Primary alkyl amines (RNH2) have been empirically used to engineer various
      colloidal semiconductor nanocrystals (NCs). Here, we present a general mechanism
      in which the amine acts as a hydrogen/proton donor in the precursor conversion to
      nanocrystals at low temperature, which was assisted by the presence of a
      secondary phosphine. Our findings introduce the strategy of using a secondary
      phosphine together with a primary amine as new routes to prepare high-quality NCs
      at low reaction temperatures but with high particle yields and reproducibility
      and thus, potentially, low production costs.

PMID- 24855038
TI  - Effect of diet on brain metabolites and behavior in spontaneously hypertensive
      rats.
AB  - Attention-deficit hyperactivity disorder (ADHD) is a heterogeneous psychiatric
      disorder affecting 5-10% of children. One of the suggested mechanisms underlying
      the pathophysiology of ADHD is insufficient energy supply to neurons. Here, we
      investigated the role of omega 3 fatty acids in altering neural energy metabolism
      and behavior of spontaneously hypertensive rats (SHR), which is an animal model
      of ADHD. To this end, we employed Proton Magnetic Resonance Spectroscopy ((1)H
      MRS) to evaluate changes in brain neurochemistry in the SHR following consumption
      of one of three experimental diets (starting PND 21): fish oil enriched (FOE),
      regular (RD) and animal fat enriched (AFE) diet. Behavioral tests were performed
      to evaluate differences in locomotor activity and risk-taking behavior (starting
      PND 44). Comparison of frontal lobe metabolites showed that increased amounts of
      omega 3 fatty acids decreased total Creatine levels (tCr), but did not change
      Glutamate (Glu), total N-Acetylaspartate (tNAA), Lactate (Lac), Choline (Cho) or
      Inositol (Ino) levels. Although behavior was not significantly affected by
      different diets, significant correlations were observed between brain metabolites
      and behavior in the open field and elevated plus maze. SHR with higher levels of
      brain tCr and Glu exhibited greater hyperactivity in a familiar environment. On
      the other hand, risk-taking exploration of the elevated plus maze's open arms
      correlated negatively with forebrain tNAA and Lac levels. These findings support
      the possible alteration in energy metabolites in ADHD, correlating with
      hyperactivity in the animal model. The data also suggest that omega 3 fatty acids
      alter brain energy and phospholipid metabolism. 

PMID- 24855041
TI  - Comparison of the incidence of vancomycin-induced nephrotoxicity in hospitalized
      patients with and without concomitant piperacillin-tazobactam.
AB  - STUDY OBJECTIVES: To determine whether the addition of piperacillin-tazobactam
      leads to an increased incidence of nephrotoxicity in patients receiving
      vancomycin and to explore potential confounding factors that may increase the
      risk of vancomycin-induced nephrotoxicity. DESIGN: Single-center, retrospective
      cohort study. SETTING: Large, academic, tertiary-care hospital. PATIENTS: One
      hundred ninety-one adults hospitalized between July 1, 2009, and July 1, 2012,
      with normal baseline renal function who received a minimum of 48 hours of
      vancomycin for any indication were included in the analysis. Of these patients,
      92 received a minimum of 48 hours of intravenous piperacillin-tazobactam
      concurrently with vancomycin, with piperacillin-tazobactam being initiated within
      48 hours of the initiation of vancomycin (combination group); 99 received
      vancomycin without piperacillin-tazobactam (vancomycin group). MEASUREMENTS AND
      MAIN RESULTS: A univariate analysis was performed to assess the effect of the
      following risk factors on the incidence of nephrotoxicity within the first 7 days
      of vancomycin treatment: concomitant nephrotoxic agents, advanced age, steady
      state vancomycin trough concentration of 15 MUg/ml or greater, elevated Charlson
      Comorbidity Index, and a total daily vancomycin dose of 4 g or greater. A
      multivariate model was constructed to compare the incidence of the primary end
      point of nephrotoxicity, defined as a minimum 1.5-fold increase in serum
      creatinine concentration, between groups. Nephrotoxicity developed in 8 (8.1%) of
      99 patients in the vancomycin group and in 15 (16.3%) of 92 patients in the
      combination group (1-sided chi(2) test, p=0.041). In the univariate analysis,
      only vancomycin trough concentration of 15 MUg/ml or greater (odds ratio 3.67)
      was associated with an increased risk of developing nephrotoxicity. In the
      multivariate analysis, patients with piperacillin-tazobactam added to vancomycin
      exhibited an increased incidence of nephrotoxicity, with an odds ratio of 2.48 (1
      sided chi(2) test, p=0.032). CONCLUSION: We observed an increased incidence of
      nephrotoxicity in vancomycin-treated patients who received concomitant
      piperacillin-tazobactam. A steady-state vancomycin trough concentration of 15
      MUg/ml or greater was also associated with an increased risk of the development
      of nephrotoxicity. These findings should be confirmed in larger, randomized
      studies.

PMID- 24855042
TI  - Quaternary ammonium salt of U50488H, a new kappa-opioid receptor agonist,
      protects rat heart against ischemia/reperfusion injury.
AB  - To keep U50488H from going through the blood-brain barrier, U50488H, a selective
      kappa-opioid receptor agonist, was structurally transformed into its quaternary
      ammonium salt (Q-U50488H). The effect of Q-U50488H on ischemic/reperfused
      myocardium and its underlying mechanisms were also investigated. U50488H was
      transformed into Q-U50488H, which was identified with mass spectrometry. The
      existences of U50488H and Q-U50488H in serum and brain tissue fluid were
      determined by high performance liquid chromatography (HPLC). SD rats' hearts were
      subjected to 30min of ischemia followed by 120min of reperfusion in vivo. After
      reperfusion, myocardial enzymes and free radicals in serum, area of myocardial
      infarction, cardiomyocyte apoptosis and the expression of Kir6.2 in rats'
      myocardium were determined. Molecular weight and solubility of Q-U50488H were
      higher than those of U50488H. Result of HPLC showed that Q-U50488H existed in
      serum but not in brain tissue after Q-U50488H intravenous injection. However,
      U50488H was detected in both serum and brain tissue. Compared with the I/R group,
      treatment with Q-U50488H significantly attenuated the activity of LDH, CK,
      AST/GOT and content of MDA in serum, upregulated the activity of SOD, and
      increased the expression of myocardial Kir6.2. It also reduced myocardial infarct
      size and cardiomyocyte apoptosis induced by I/R. Moreover, pretreatment with Nor
      BNI (a selective kappa-opioid receptor antagonist), 5-HD and glibenclamide (KATP
      antagonists) abolished the effects of Q-U50488H. It is suggested Q-U50488H, a new
      compound of kappa-opioid receptor agonist, which is not able to pass the blood
      brain barrier, elicits a protective effect against myocardial
      ischemia/reperfusion injury. The cardioprotective effect of Q-U50488H is
      associated with the opening of KATP. 

PMID- 24855043
TI  - Pencil beam scanning dosimetry for large animal irradiation.
AB  - The space radiation environment imposes increased dangers of exposure to ionizing
      radiation, particularly during a solar particle event. These events consist
      primarily of low-energy protons that produce a highly inhomogeneous depth-dose
      distribution. Here we describe a novel technique that uses pencil beam scanning
      at extended source-to-surface distances and range shifter (RS) to provide robust
      but easily modifiable delivery of simulated solar particle event radiation to
      large animals. Thorough characterization of spot profiles as a function of
      energy, distance and RS position is critical to accurate treatment planning. At
      105 MeV, the spot sigma is 234 mm at 4800 mm from the isocentre when the RS is
      installed at the nozzle. With the energy increased to 220 MeV, the spot sigma is
      66 mm. At a distance of 1200 mm from the isocentre, the Gaussian sigma is 68 mm
      and 23 mm at 105 MeV and 220 MeV, respectively, when the RS is located on the
      nozzle. At lower energies, the spot sigma exhibits large differences as a
      function of distance and RS position. Scan areas of 1400 mm (superior-inferior)
      by 940 mm (anterior-posterior) and 580 mm by 320 mm are achieved at the extended
      distances of 4800 mm and 1200 mm, respectively, with dose inhomogeneity <2%. To
      treat large animals with a more sophisticated dose distribution, spot size can be
      reduced by placing the RS closer than 70 mm to the surface of the animals,
      producing spot sigmas below 6 mm. 

PMID- 24855044
TI  - CCS mRNA transcripts and serum CCS protein as copper marker in adults suffering
      inflammatory processes.
AB  - The chaperone to Zn-Cu superoxide dismutase (CCS) has been postulated as a
      candidate copper indicator, changing in a consistent manner in induced and
      recovered copper deficiency, in experimental cell and animal models. In real life
      people have various conditions that may modify molecules acting as acute phase
      proteins, such as serum ceruloplasmin and copper concentration and could alter
      CCS responses. With the hypothesis that CCS mRNA transcripts and protein would be
      different in individuals suffering inflammatory processes in comparison to
      healthy individuals, we assessed adult individuals who, although not ill had
      conditions known to induce variable degrees of inflammation. Screening of 600
      adults resulted in two study groups, formed on the basis of their clinical
      history and levels of serum C reactive protein (CRP): Group 1 (n = 61, mean
      (range) CRP = 0.9 (0.3-2.0 mg/dL) and Group 2 (n = 150, mean (range) CRP = 6.1
      (4.3-8.7 mg/dL). Results showed that mRNA transcripts relative abundance was not
      different for CCS, MTIIA, TNF-alpha and Cu-Zn-SOD by group (p > 0.05, one way
      Anova), nor between sexes (p > 0.05, one way Anova). Distribution of CCS mRNA
      transcripts and CCS protein in serum did not show any differences or trends.
      Results disproved our hypothesis that CCS abundance of transcripts and CCS
      protein would be different in individuals suffering inflammatory processes,
      adding further support to the idea that CCS may be a copper marker. 

PMID- 24855045
TI  - Monocular distance estimation from optic flow during active landing maneuvers.
AB  - Vision is arguably the most widely used sensor for position and velocity
      estimation in animals, and it is increasingly used in robotic systems as well.
      Many animals use stereopsis and object recognition in order to make a true
      estimate of distance. For a tiny insect such as a fruit fly or honeybee, however,
      these methods fall short. Instead, an insect must rely on calculations of optic
      flow, which can provide a measure of the ratio of velocity to distance, but not
      either parameter independently. Nevertheless, flies and other insects are adept
      at landing on a variety of substrates, a behavior that inherently requires some
      form of distance estimation in order to trigger distance-appropriate motor
      actions such as deceleration or leg extension. Previous studies have shown that
      these behaviors are indeed under visual control, raising the question: how does
      an insect estimate distance solely using optic flow? In this paper we use a
      nonlinear control theoretic approach to propose a solution for this problem. Our
      algorithm takes advantage of visually controlled landing trajectories that have
      been observed in flies and honeybees. Finally, we implement our algorithm, which
      we term dynamic peering, using a camera mounted to a linear stage to demonstrate
      its real-world feasibility. 

PMID- 24855047
TI  - Prevention and management of co-morbidities in SLE.
AB  - The prognosis and survival of patients with systemic lupus erythematosus (SLE)
      have improved over the past few decades. The major cause of death is no longer
      active lupus, but instead cardiovascular disease, complications of renal failure,
      and malignancy. Co-morbid factors, including both traditional and non-traditional
      cardiovascular risk factors, can be targeted according to accepted guidelines. We
      will emphasize the deleterious effect of corticosteroids in contributing to
      cardiovascular risk and the need to shift maintenance prednisone doses to a much
      lower threshold. 

PMID- 24855046
TI  - Medical students and personal smartphones in the clinical environment: the impact
      on confidentiality of personal health information and professionalism.
AB  - BACKGROUND: Smartphones are becoming ubiquitous in health care settings. The
      increased adoption of mobile technology such as smartphones may be attributed to
      their use as a point-of-care information source and to perceived improvements in
      clinical communication and efficiency. However, little is known about medical
      students' use of personal smartphones for clinical work. OBJECTIVE: The intent of
      the study was to examine final-year medical students' experience with and
      attitudes toward using personal mobile technology in the clinical environment,
      with respect to the perceived impact on patient confidentiality and provider
      professionalism. METHODS: Cross-sectional surveys were completed by final-year
      medical students at the University of Toronto. Respondents were asked about the
      type of personal mobile phone they use, security features on their personal
      phone, experiences using their personal phone during clinical rotations, and
      attitudes about using their personal phone for clinical work purposes. RESULTS:
      The overall response rate was 45.4% (99/218). Smartphone ownership was prevalent
      (98%, 97/99) with the majority (86%, 85/99) of participants using their personal
      phones for patient-related communication during clinical rotations. A total of
      26% (26/99) of participants reported not having any type of security feature on
      their personal phone, 94% (90/96) of participants agreed that using their
      personal phone for clinical work makes them more efficient, and 86% (82/95)
      agreed that their personal phone allows them to provide better patient care.
      Although 68% (65/95) of participants believe that the use of personal phones for
      patient-related communication with colleagues poses a risk to the privacy and
      confidentiality of patient health information, 22% (21/96) of participants still
      use their personal phone to text or email identifiable patient data to
      colleagues. CONCLUSIONS: Our findings suggest that the use of personal
      smartphones for clinical work by medical students is prevalent. There is a need
      to more fully address the threat to patient confidentiality posed by the use of
      unsecured communication devices such as smartphones.

PMID- 24855048
TI  - Hydroxychloroquine: a multifaceted treatment in lupus.
AB  - The efficacy of antimalarials, especially hydroxychloroquine (HCQ), in preventing
      systemic lupus erythematosus (SLE) flares is well demonstrated. However, many
      studies show that the percentage of SLE patients treated with HCQ remains low. By
      blocking the toll-like receptor 7 and 9 in plasmacytoid dendritic cells, HCQ
      inhibits interferon-alpha production which plays a crucial role in SLE
      pathogenesis. In addition to reducing damage accrual in SLE patients, HCQ appears
      to protect against the occurrence of diabetes, thrombotic events, and
      dyslipidemia. As a consequence, some studies have suggested that HCQ, which is
      inexpensive, has a protective effect on survival in SLE patients. Thanks to the
      pharmacokinetic properties of HCQ (long half-life) and to the availability of its
      blood assay, very low or undetectable blood HCQ concentrations are a valuable
      marker of non-adherence to treatment, thus adding a new benefit to HCQ
      prescriptions. The main side effect of HCQ is retinal toxicity. This complication
      is very rare, but may be potentially severe, thus requiring regular screening.
      Retinal toxicity remains the only absolute contra-indication of HCQ in adult SLE
      patients. Other contra-indications are few and rare. During pregnancy and breast
      feeding, HCQ continuation is not only allowed but recommended. In conclusion, the
      risk/benefit ratio of HCQ is excellent. Many now believe that all SLE patients
      should be offered this treatment.

PMID- 24855049
TI  - [Maternal and perinatal infections to Streptococcus agalactiae].
AB  - Streptococcus agalactiae (Group B Streptococcus, GBS) is a Gram-positive
      encapsulated bacterium, found in the digestive and vaginal tracts of 20-30%
      healthy individuals. It is the leading cause of neonatal invasive infections
      (septicaemia and meningitis). Two GBS-associated syndromes have been recognized
      in neonates, the early-onset disease (EOD) and the late-onset disease (LOD),
      which occur in the first week of life (age 0-6 days) and after (age 7 days-3
      months), respectively. Since the establishment of early antibiotic prophylaxis
      there has been a decrease in the incidence of EOD. However, LOD incidence remains
      stable. Epidemiological studies revealed a strong association between LOD and a
      single capsular serotype III ST-17 clone. This ST-17 clone, referred to as the
      "hypervirulent" clone, possesses specific virulence factors that could account
      for its increased virulence and neonatal tropism. Conjugate vaccines directed
      against several capsular serotypes are being developed to prevent invasive
      disease. However, hypervirulent strains having made a switch to a capsular
      serotype not covered by such vaccines are emerging, reinforcing the need to
      identify new candidate vaccines.

PMID- 24855051
TI  - Hawkmoth flight performance in tornado-like whirlwind vortices.
AB  - Vertical vortex systems such as tornadoes dramatically affect the flight control
      and stability of aircraft. However, the control implications of smaller scale
      vertically oriented vortex systems for small fliers such as animals or micro-air
      vehicles are unknown. Here we examined the flapping kinematics and body dynamics
      of hawkmoths performing hovering flights (controls) and maintaining position in
      three different whirlwind intensities with transverse horizontal velocities of
      0.7, 0.9 and 1.2 m s(-1), respectively, generated in a vortex chamber. The
      average and standard deviation of yaw and pitch were respectively increased and
      reduced in comparison with hovering flights. Average roll orientation was
      unchanged in whirlwind flights but was more variable from wingbeat to wingbeat
      than in hovering. Flapping frequency remained unchanged. Wingbeat amplitude was
      lower and the average stroke plane angle was higher. Asymmetry was found in the
      angle of attack between right and left wings during both downstroke and upstroke
      at medium and high vortex intensities. Thus, hawkmoth flight control in tornado
      like vortices is achieved by a suite of asymmetric and symmetric changes to
      wingbeat amplitude, stroke plane angle and principally angle of attack. 

PMID- 24855052
TI  - Adaptive control of a millimeter-scale flapping-wing robot.
AB  - Challenges for the controlled flight of a robotic insect are due to the inherent
      instability of the system, complex fluid-structure interactions, and the general
      lack of a complete system model. In this paper, we propose theoretical models of
      the system based on the limited information available from previous work and a
      comprehensive flight controller. The modular flight controller is derived from
      Lyapunov function candidates with proven stability over a large region of
      attraction. Moreover, it comprises adaptive components that are capable of coping
      with uncertainties in the system that arise from manufacturing imperfections. We
      have demonstrated that the proposed methods enable the robot to achieve sustained
      hovering flights with relatively small errors compared to a non-adaptive
      approach. Simple lateral maneuvers and vertical takeoff and landing flights are
      also shown to illustrate the fidelity of the flight controller. The analysis
      suggests that the adaptive scheme is crucial in order to achieve millimeter-scale
      precision in flight control as observed in natural insect flight. 

PMID- 24855050
TI  - Low levels of circulating T-regulatory lymphocytes and short cervical length are
      associated with preterm labor.
AB  - Recent discoveries suggest that T-regulatory lymphocytes (Treg) might play an
      important role in the pathophysiology of preterm labor. The aim of this study was
      to assess the relationship among the levels of maternal circulating Treg cells,
      uterine cervical length, and the risk of preterm labor. Sixty women with regular
      contractions and/or cervical incompetence at 24-32 weeks' gestation were
      recruited into a prospective study. Each patient underwent transvaginal
      ultrasound examination of the cervical length, and regulatory T cells were
      quantified in peripheral blood samples by flow cytometry. Patients with cervical
      incompetence were prescribed vaginal progesterone until birth. Measurements of
      Treg levels and cervical length correlated with the timing of labor. The risk of
      preterm labor happening within 48 h of testing was demonstrated to be almost 35
      times higher (OR=35.21, CI 13.3; 214, p<0.001) in the group with simultaneously
      low Treg values (<0.031 * 10(9)/L) and a shortened uterine cervix (<17.5mm),
      compared with the situation where both of these values were normal. Similar
      results were found in predicting preterm delivery before 34 weeks, or between 34
      and 37 weeks. A statistically nonsignificant trend toward increased cervical
      length and increased Treg count was noted in the women on progesterone treatment.
      We show for the first time that the combined assessment of Treg cell count and
      cervical length is a much better predictor of preterm delivery than either
      parameter used on its own. This combined approach may offer clinical application
      in patients who present with risk factors for preterm labor.

PMID- 24855054
TI  - Phylloquinone concentrations and the risk of vascular calcification in healthy
      women.
AB  - OBJECTIVE: To investigate the association of plasma phylloquinone concentrations
      with coronary artery calcification (CAC) and vascular calcification. APPROACH AND
      RESULTS: In a prospective cohort of 508 postmenopausal women, plasma
      phylloquinone concentrations were measured by high-pressure liquid
      chromatography. Calcification was measured in the coronary arteries, aortic
      valve, mitral valve, and thoracic aorta by multidetector computed tomography. To
      combine these calcification scores, we dichotomized each of the 4 areas into
      present or absent. Because of the continuous measurement of CAC, we categorized
      this as calcification present if Agatston score was >0, and calcification score
      was calculated as the sum of the calcified areas. Multivariate-adjusted
      prevalence ratios and odds ratios were estimated using Poisson regression and
      multinomial logistic regression. After 8.5 years of follow-up, 22% of the women
      had no calcification, whereas 5% had calcification in all measured areas.
      Detectable phylloquinone concentrations were associated with increased CAC
      compared with nondetectable phylloquinone concentrations with a prevalence ratio
      of 1.34 (95% confidence interval, 1.01-1.77). When dividing women with detectable
      phylloquinone concentrations into low detectable (>0-0.70 nmol/L) and moderate to
      high detectable (>0.70 nmol/L) phylloquinone concentrations versus nondetectable
      phylloquinone concentrations, both were associated with increased CAC with a
      prevalence ratio of 1.32 (95% confidence interval, 0.99-1.76) and 1.36 (95%
      confidence interval, 1.02-1.81), respectively. Detectable phylloquinone
      concentrations were not associated with the number of calcified areas with an
      odds ratio(no versus >= 3 areas calcifications) of 1.60 (95% confidence interval,
      0.65-3.99; P=0.31). CONCLUSIONS: Detectable phylloquinone concentrations are not
      associated with reduced vascular calcification but seemed to be associated with
      an increased prevalence of CAC.

PMID- 24855053
TI  - Endothelial cell-specific expression of roundabout 4 is regulated by differential
      DNA methylation of the proximal promoter.
AB  - OBJECTIVE: The molecular basis of endothelial cell (EC)-specific gene expression
      is poorly understood. Roundabout 4 (Robo4) is expressed exclusively in ECs. We
      previously reported that the 3-kb 5'-flanking region of the human Robo4 gene
      contains information for lineage-specific expression in the ECs. Our studies
      implicated a critical role for GA-binding protein and specificity protein 1 (SP1)
      in mediating overall expression levels. However, these transcription factors are
      also expressed in non-ECs. In this study, we tested the hypothesis that
      epigenetic mechanisms contribute to EC-specific Robo4 gene expression. METHODS
      AND RESULTS: Bisulfite sequencing analysis indicated that the proximal promoter
      of Robo4 is methylated in non-ECs but not in ECs. Treatment with the DNA
      methyltransferase inhibitor 5-aza-2'-deoxycytidine increased Robo4 gene
      expression in non-ECs but not in ECs. Proximal promoter methylation significantly
      decreased the promoter activity in ECs. Electrophoretic mobility shift assays
      showed that DNA methylation of the proximal promoter inhibited SP1 binding to the
      -42 SP1 site. In DNase hypersensitivity assays, chromatin condensation of the
      Robo4 promoter was observed in some but not all nonexpressing cell types. In Hprt
      (hypoxanthine phosphoribosyltransferase)-targeted mice, a 0.3-kb proximal
      promoter directed cell-type-specific expression in the endothelium. Bisulfite
      sequencing analysis using embryonic stem cell-derived mesodermal cells and ECs
      indicated that the EC-specific methylation pattern of the promoter is determined
      by demethylation during differentiation and that binding of GA-binding protein
      and SP1 to the proximal promoter is not essential for demethylation. CONCLUSIONS:
      The EC-specific DNA methylation pattern of the Robo4 proximal promoter is
      determined during cell differentiation and contributes to regulation of EC
      specific Robo4 gene expression.

PMID- 24855056
TI  - Endothelial AMP-activated protein kinase regulates blood pressure and coronary
      flow responses through hyperpolarization mechanism in mice.
AB  - OBJECTIVE: Vascular endothelium plays an important role to maintain
      cardiovascular homeostasis through several mechanisms, including endothelium
      dependent hyperpolarization (EDH). We have recently demonstrated that EDH is
      involved in endothelial metabolic regulation in mice. However, it remains to be
      examined whether AMP-activated protein kinase (AMPK), an important metabolic
      regulator, is involved in EDH and if so, whether endothelial AMPK (eAMPK) plays a
      role for circulatory regulation. APPROACH AND RESULTS: We examined the role of
      eAMPK in EDH, using mice with endothelium-specific deficiency of alpha-catalytic
      subunit of AMPK, either alpha1 (eAMPKalpha1 (-/-)alpha2 (+/+)) or alpha2
      (eAMPKalpha1 (+/+)alpha2 (-/-)) alone or both of them (eAMPKalpha1 (-/-)alpha2 (
      /-)). We performed telemetry, organ chamber, electrophysiological, and
      Langendorff experiments to examine blood pressure, vascular responses,
      hyperpolarization of membrane potential, and coronary flow responses,
      respectively. Hypertension was noted throughout the day in eAMPKalpha1 (-/
      )alpha2 (-/-) and eAMPKalpha1 (-/-)alpha2 (+/+) but not in eAMPKalpha1
      (+/+)alpha2 (-/-) mice when compared with respective control. Importantly,
      endothelium-dependent relaxations, EDH, and coronary flow increase were all
      significantly reduced in eAMPKalpha1 (-/-)alpha2 (-/-) and eAMPKalpha1 (-/
      )alpha2 (+/+) but not in eAMPKalpha1 (+/+)alpha2 (-/-) mice. In contrast,
      endothelium-independent relaxations to sodium nitroprusside (a NO donor), NS-1619
      (a Ca(2+)-activated K(+) channel opener), and exogenous H2O2 were almost
      comparable among the groups. In eAMPKalpha1 (-/-)alpha2 (-/-) mice,
      antihypertensive treatment with hydralazine or long-term treatment with metformin
      (a stimulator of AMPK) failed to restore EDH-mediated responses. CONCLUSIONS:
      These results provide the first direct evidence that alpha1 subunit of eAMPK
      substantially mediates EDH responses of microvessels and regulates blood pressure
      and coronary flow responses in mice in vivo, demonstrating the novel role of
      eAMPK in cardiovascular homeostasis.

PMID- 24855055
TI  - CXCR6 plays a critical role in angiotensin II-induced renal injury and fibrosis.
AB  - OBJECTIVE: Recent studies have shown that angiotensin II (Ang II) plays a
      critical role in the pathogenesis and progression of hypertensive kidney disease.
      However, the signaling mechanisms are poorly understood. In this study, we
      investigated the role of CXCR6 in Ang II-induced renal injury and fibrosis.
      APPROACH AND RESULTS: Wild-type and CXCR6-green fluorescent protein (GFP) knockin
      mice were treated with Ang II via subcutaneous osmotic minipumps at 1500 ng/kg
      per minute after unilateral nephrectomy for <= 4 weeks. Wild-type and CXCR6-GFP
      knockin mice had virtually identical blood pressure at baseline. Ang II treatment
      led to an increase in blood pressure that was similar between wild-type and CXCR6
      GFP knockin mice. CXCR6-GFP knockin mice were protected from Ang II-induced renal
      dysfunction, proteinuria, and fibrosis. CXCR6-GFP knockin mice accumulated fewer
      bone marrow-derived fibroblasts and myofibroblasts and produced less
      extracellular matrix protein in the kidneys after Ang II treatment. Furthermore,
      CXCR6-GFP knockin mice exhibited fewer F4/80(+) macrophages and CD3(+) T cells
      and expressed less proinflammatory cytokines in the kidneys after Ang II
      treatment. Finally, wild-type mice engrafted with CXCR6(-/-) bone marrow cells
      displayed fewer bone marrow-derived fibroblasts, macrophages, and T cells in the
      kidney after Ang II treatment when compared with wild-type mice engrafted with
      CXCR6(+/+) bone marrow cells. CONCLUSIONS: Our results indicate that CXCR6 plays
      a pivotal role in the development of Ang II-induced renal injury and fibrosis
      through regulation of macrophage and T-cell infiltration and bone marrow-derived
      fibroblast accumulation.

PMID- 24855057
TI  - Functional assembly of Kv7.1/Kv7.5 channels with emerging properties on vascular
      muscle physiology.
AB  - OBJECTIVE: Voltage-dependent K(+) (Kv) channels from the Kv7 family are expressed
      in blood vessels and contribute to cardiovascular physiology. Although Kv7
      channel blockers trigger muscle contractions, Kv7 activators act as
      vasorelaxants. Kv7.1 and Kv7.5 are expressed in many vessels. Kv7.1 is under
      intense investigation because Kv7.1 blockers fail to modulate smooth muscle
      reactivity. In this study, we analyzed whether Kv7.1 and Kv7.5 may form
      functional heterotetrameric channels increasing the channel diversity in vascular
      smooth muscles. APPROACH AND RESULTS: Kv7.1 and Kv7.5 currents elicited in
      arterial myocytes, oocyte, and mammalian expression systems suggest the formation
      of heterotetrameric complexes. Kv7.1/Kv7.5 heteromers, exhibiting different
      pharmacological characteristics, participate in the arterial tone. Kv7.1/Kv7.5
      associations were confirmed by coimmunoprecipitation, fluorescence resonance
      energy transfer, and fluorescence recovery after photobleaching experiments.
      Kv7.1/Kv7.5 heterotetramers were highly retained at the endoplasmic reticulum.
      Studies in HEK-293 cells, heart, brain, and smooth and skeletal muscles
      demonstrated that the predominant presence of Kv7.5 stimulates release of
      Kv7.1/Kv7.5 oligomers out of lipid raft microdomains. Electrophysiological
      studies supported that KCNE1 and KCNE3 regulatory subunits further increased the
      channel diversity. Finally, the analysis of rat isolated myocytes and human blood
      vessels demonstrated that Kv7.1 and Kv7.5 exhibited a differential expression,
      which may lead to channel diversity. CONCLUSIONS: Kv7.1 and Kv7.5 form
      heterotetrameric channels increasing the diversity of structures which fine-tune
      blood vessel reactivity. Because the lipid raft localization of ion channels is
      crucial for cardiovascular physiology, Kv7.1/Kv7.5 heteromers provide efficient
      spatial and temporal regulation of smooth muscle function. Our results shed light
      on the debate about the contribution of Kv7 channels to vasoconstriction and
      hypertension.

PMID- 24855058
TI  - Factor XII regulates the pathological process of thrombus formation on ruptured
      plaques.
AB  - OBJECTIVE: Atherothrombosis is the main cause of myocardial infarction and
      ischemic stroke. Although the extrinsic (tissue factor-factor VIIa [FVIIa])
      pathway is considered as a major trigger of coagulation in atherothrombosis, the
      role of the intrinsic coagulation pathway via coagulation FXII herein is unknown.
      Here, we studied the roles of the extrinsic and intrinsic coagulation pathways in
      thrombus formation on atherosclerotic plaques both in vivo and ex vivo. APPROACH
      AND RESULTS: Plaque rupture after ultrasound treatment evoked immediate formation
      of subocclusive thrombi in the carotid arteries of Apoe(-/-) mice, which became
      unstable in the presence of structurally different FXIIa inhibitors. In contrast,
      inhibition of FVIIa reduced thrombus size at a more initial stage without
      affecting embolization. Genetic deficiency in FXII (human and mouse) or FXI
      (mouse) reduced ex vivo whole-blood thrombus and fibrin formation on immobilized
      plaque homogenates. Localization studies by confocal microscopy indicated that
      FXIIa bound to thrombi and fibrin particularly in luminal-exposed thrombus areas.
      CONCLUSIONS: The FVIIa- and FXIIa-triggered coagulation pathways have distinct
      but complementary roles in atherothrombus formation. The tissue factor-FVIIa
      pathway contributes to initial thrombus buildup, whereas FXIIa bound to thrombi
      ensures thrombus stability.

PMID- 24855059
TI  - S100/Calgranulin-mediated inflammation accelerates left ventricular hypertrophy
      and aortic valve sclerosis in chronic kidney disease in a receptor for advanced
      glycation end products-dependent manner.
AB  - OBJECTIVE: S100A12 and fibroblast growth factor 23 are biomarkers of
      cardiovascular morbidity and mortality in patients with chronic kidney disease
      (CKD). We tested the hypothesis that human S100/calgranulin would accelerate
      cardiovascular disease in mice subjected to CKD. APPROACH AND RESULTS: A
      bacterial artificial chromosome of the human S100/calgranulin gene cluster
      containing the genes and regulatory elements for S100A8, S100A9, and S100A12 was
      expressed in C57BL/6J mouse (hBAC-S100) to generate a novel humanized mouse
      model. CKD was induced by ureteral ligation, and hBAC-S100 mice and wild-type
      mice were studied after 10 weeks of chronic uremia. hBAC-S100 mice with CKD
      showed increased fibroblast growth factor 23 in the hearts, left ventricular
      hypertrophy, diastolic dysfunction, focal cartilaginous metaplasia, and
      calcification of the mitral and aortic valve annulus together with aortic valve
      sclerosis. This phenotype was not observed in wild-type mice with CKD or in hBAC
      S100 mice lacking the receptor for advanced glycation end products with CKD,
      suggesting that the inflammatory milieu mediated by S100/receptor for advanced
      glycation end products promotes pathological cardiac hypertrophy in CKD. In
      vitro, inflammatory stimuli including interleukin-6, tumor necrosis factor-alpha,
      lipopolysaccarides, or serum from hBAC-S100 mice upregulated fibroblast growth
      factor 23 mRNA and protein in primary murine neonatal and adult cardiac
      fibroblasts. CONCLUSIONS: Myeloid-derived human S100/calgranulin is associated
      with the development of cardiac hypertrophy and ectopic cardiac calcification in
      a receptor for advanced glycation end products-dependent manner in a mouse model
      of CKD. We speculate that fibroblast growth factor 23 produced by cardiac
      fibroblasts in response to cytokines may act in a paracrine manner to accelerate
      left ventricular hypertrophy and diastolic dysfunction in hBAC-S100 mice with
      CKD.

PMID- 24855061
TI  - Sequence variation in vitamin K epoxide reductase gene is associated with
      survival and progressive coronary calcification in chronic kidney disease.
AB  - OBJECTIVE: Sequence variations in the gene(s) encoding vitamin K epoxide
      reductase complex subunit 1 (VKORC1), the enzyme target of warfarin, have been
      associated with increased cardiovascular disease in the general population.
      Coronary artery calcification (CAC) is a prevalent form of cardiovascular disease
      in chronic kidney disease. We tested the hypothesis that the VKORC1 rs8050894 CC
      genotype would be associated with mortality and progression of CAC <= 4 years.
      APPROACH AND RESULTS: This study is an observational, prospective study of 167
      individuals with stages 3 to 5 chronic kidney disease. Survival <= 4 years was
      assessed in all participants, and CAC progression was measured in a subset of 86
      patients. Participants with the CG/GG genotype of VKORC1 had higher baseline CAC
      scores (median score, 112 versus 299; P=0.036). Of those 86 patients who had a 4
      year CAC score, those with the CG/GG genotype had an increased risk of
      progressive CAC (adjusted for age, diabetes mellitus, estimated glomerular
      filtration rate, and hypertension) compared with those with the CC genotype. Four
      year mortality risk was 4 times higher for individuals with the CG/GG genotypes
      compared with individuals with the CC genotype (odds ratio, 3.8; 95% confidence
      interval, 1.2-12.5; P=0.02), adjusted for age, sex, diabetes mellitus, estimated
      glomerular filtration rate, baseline CAC, and hypertension. CONCLUSIONS: Patients
      with the CG/GG genotype of VKORC1 had a higher risk of CAC progression and a
      poorer survival. These data provide new perspectives on the potential
      extrahepatic role of VKORC1 in individuals with chronic kidney disease.

PMID- 24855060
TI  - MicroRNA-23b regulates cyclin-dependent kinase-activating kinase complex through
      cyclin H repression to modulate endothelial transcription and growth under flow.
AB  - OBJECTIVE: The site-specificity of endothelial phenotype is attributable to the
      local hemodynamic forces. The flow regulation of microRNAs in endothelial cells
      (ECs) plays a significant role in vascular homeostasis and diseases. The
      objective of this study was to elucidate the molecular mechanism by which the
      pulsatile shear flow-induced microRNA-23b (miR-23b) exerts antiproliferative
      effects on ECs. APPROACH AND RESULTS: We used a combination of a cell perfusion
      system and experimental animals to examine the flow regulation of miR-23b in
      modulating EC proliferation. Our results demonstrated that pulsatile shear flow
      induces the transcription factor Kruppel-like factor 2 to promote miR-23b
      biosynthesis; the increase in miR-23b then represses cyclin H to impair the
      activity and integrity of cyclin-dependent kinase-activating kinase (CAK)
      complex. The inhibitory effect of miR-23b on CAK exerts dual actions to suppress
      cell cycle progression, and reduce basal transcription by deactivating RNA
      polymerase II. Whereas pulsatile shear flow regulates the miR-23b/CAK pathway to
      exert antiproliferative effects on ECs, oscillatory shear flow has little effect
      on the miR-23b/CAK pathway and hence does not cause EC growth arrest. Such flow
      pattern-dependent phenomena are validated with an in vivo model on rat carotid
      artery: the flow disturbance induced by partial carotid ligation led to a lower
      expression of miR-23b and a higher EC proliferation in comparison with the
      pulsatile flow regions of the unligated vessels. Local delivery of miR-23b
      mitigated the proliferative EC phenotype in partially ligated vessels.
      CONCLUSIONS: Our findings unveil a novel mechanism by which hemodynamic forces
      modulate EC proliferative phenotype through the miR-23b/CAK pathway.

PMID- 24855062
TI  - Mechanisms of adiponectin-associated perivascular function in vascular disease.
AB  - The concept that fat cells could influence the circulation and indeed cardiac
      function has been in existence for >=20 years and has gained a wide interest and
      no less excitement as evidence has accrued to suggest that such effects may be
      profound enough to explain disease states, such as hypertension and metabolic
      changes associated with obesity and type II diabetes mellitus. This ATVB in Focus
      intends to examine our current knowledge in this field, and suggests mechanisms
      that may be responsible for normal perivascular function and how they become
      disordered in obesity. There is the tantalizing prospect of developing new
      therapeutic approaches to keep obese individuals healthy and redesignating type
      II diabetes mellitus as a vascular disease. 

PMID- 24855064
TI  - Fluid-structure interaction in compliant insect wings.
AB  - Insect wings deform significantly during flight. As a result, wings act as
      aeroelastic structures wherein both the driving motion of the structure and the
      aerodynamic loading of the surrounding fluid potentially interact to modify wing
      shape. We explore two key issues associated with the design of compliant wings:
      over a range of driving frequencies and phases of pitch-heave actuation, how does
      wing stiffness influence (1) the lift and thrust generated and (2) the relative
      importance of fluid loading on the shape of the wing? In order to examine a wide
      range of parameters relevant to insect flight, we develop a computationally
      efficient, two-dimensional model that couples point vortex methods for fluid
      force computations with structural finite element methods to model the fluid
      structure interaction of a wing in air. We vary the actuation frequency, phase of
      actuation, and flexural stiffness over a range that encompasses values measured
      for a number of insect taxa (10-90 Hz; 0-pi rad; 10(-7)-10(-5) N m(2)). We show
      that the coefficients of lift and thrust are maximized at the first and second
      structural resonant frequencies of the system. We also show that even in regions
      of structural resonance, fluid loading never contributes more than 20% to the
      development of flight forces. 

PMID- 24855063
TI  - Polymerase delta-interacting protein 2 promotes postischemic neovascularization
      of the mouse hindlimb.
AB  - OBJECTIVE: Collateral vessel formation can functionally compensate for
      obstructive vascular lesions in patients with atherosclerosis. Neovascularization
      processes are triggered by fluid shear stress, hypoxia, growth factors,
      chemokines, proteases, and inflammation, as well as reactive oxygen species, in
      response to ischemia. Polymerase delta-interacting protein 2 (Poldip2) is a
      multifunctional protein that regulates focal adhesion turnover and vascular
      smooth muscle cell migration and modifies extracellular matrix composition. We,
      therefore, tested the hypothesis that loss of Poldip2 impairs collateral
      formation. APPROACH AND RESULTS: The mouse hindlimb ischemia model has been used
      to understand mechanisms involved in postnatal blood vessel formation. Poldip2(+/
      ) mice were subjected to femoral artery excision, and functional and
      morphological analysis of blood vessel formation was performed after injury.
      Heterozygous deletion of Poldip2 decreased the blood flow recovery and
      spontaneous running activity at 21 days after injury. H2O2 production, as well as
      the activity of matrix metalloproteinases-2 and -9, was reduced in these animals
      compared with Poldip2(+/+) mice. Infiltration of macrophages in the peri-injury
      muscle was also decreased; however, macrophage phenotype was similar between
      genotypes. In addition, the formation of capillaries and arterioles was impaired,
      as was angiogenesis, in agreement with a decrease in proliferation observed in
      endothelial cells treated with small interfering RNA against Poldip2. Finally,
      regression of newly formed vessels and apoptosis was more pronounced in
      Poldip2(+/-) mice. CONCLUSIONS: Together, these results suggest that Poldip2
      promotes ischemia-induced collateral vessel formation via multiple mechanisms
      that likely involve reactive oxygen species-dependent activation of matrix
      metalloproteinase activity, as well as enhanced vascular cell growth and
      survival.

PMID- 24855067
TI  - Leading edge vortices in lesser long-nosed bats occurring at slow but not fast
      flight speeds.
AB  - Slow and hovering animal flight creates high demands on the lift production of
      animal wings. Steady state aerodynamics is unable to explain the forces required
      and the most commonly used mechanism to enhance the lift production is a leading
      edge vortex (LEV). Although LEVs increase the lift, they come at the cost of high
      drag. Here we determine the flow above the wing of lesser long-nosed bats at slow
      and cruising speed using particle image velocimetry (PIV). We find that a
      prominent LEV is present during the downstroke at slow speed, but not at cruising
      speed. Comparison with previously published LEV data from a robotic flapper
      inspired by lesser long-nosed bats suggests that bats should be able to generate
      LEVs at cruising speeds, but that they avoid doing so, probably to increase
      flight efficiency. In addition, at slow flight speeds we find LEVs of opposite
      spin at the inner and outer wing during the upstroke, potentially providing a
      control challenge to the animal. We also note that the LEV stays attached to the
      wing throughout the downstoke and does not show the complex structures found in
      insects. This suggests that bats are able to control the development of the LEV
      and potential control mechanisms are discussed. 

PMID- 24855068
TI  - On the limits of computational functional genomics for bacterial lifestyle
      prediction.
AB  - We review the level of genomic specificity regarding actinobacterial
      pathogenicity. As they occupy various niches in diverse habitats, one may assume
      the existence of lifestyle-specific genomic features. We include 240
      actinobacteria classified into four pathogenicity classes: human pathogens (HPs),
      broad-spectrum pathogens (BPs), opportunistic pathogens (OPs) and non-pathogenic
      (NP). We hypothesize: (H1) Pathogens (HPs and BPs) possess specific pathogenicity
      signature genes. (H2) The same holds for OPs. (H3) Broad-spectrum and exclusively
      HPs cannot be distinguished from each other because of an observation bias, i.e.
      many HPs might yet be unclassified BPs. (H4) There is no intrinsic genomic
      characteristic of OPs compared with pathogens, as small mutations are likely to
      play a more dominant role to survive the immune system. To study these
      hypotheses, we implemented a bioinformatics pipeline that combines evolutionary
      sequence analysis with statistical learning methods (Random Forest with feature
      selection, model tuning and robustness analysis). Essentially, we present
      orthologous gene sets that computationally distinguish pathogens from NPs (H1).
      We further show a clear limit in differentiating OPs from both NPs (H2) and
      pathogens (H4). HPs may also not be distinguished from bacteria annotated as BPs
      based only on a small set of orthologous genes (H3), as many HPs might as well
      target a broad range of mammals but have not been annotated accordingly. In
      conclusion, we illustrate that even in the post-genome era and despite next
      generation sequencing technology, our ability to efficiently deduce real-world
      conclusions, such as pathogenicity classification, remains quite limited. 

PMID- 24855066
TI  - Specific glycosylation of membrane proteins in epithelial ovarian cancer cell
      lines: glycan structures reflect gene expression and DNA methylation status.
AB  - Epithelial ovarian cancer is the fifth most common cause of cancer in women
      worldwide bearing the highest mortality rate among all gynecological cancers.
      Cell membrane glycans mediate various cellular processes such as cell signaling
      and become altered during carcinogenesis. The extent to which glycosylation
      changes are influenced by aberrant regulation of gene expression is nearly
      unknown for ovarian cancer and remains crucial in understanding the development
      and progression of this disease. To address this effect, we analyzed the membrane
      glycosylation of non-cancerous ovarian surface epithelial (HOSE 6.3 and HOSE
      17.1) and serous ovarian cancer cell lines (SKOV 3, IGROV1, A2780, and OVCAR 3),
      the most common histotype among epithelial ovarian cancers. N-glycans were
      released from membrane glycoproteins by PNGase F and analyzed using nano-liquid
      chromatography on porous graphitized carbon and negative-ion electrospray
      ionization mass spectrometry (ESI-MS). Glycan structures were characterized based
      on their molecular masses and tandem MS fragmentation patterns. We identified
      characteristic glycan features that were unique to the ovarian cancer membrane
      proteins, namely the "bisecting N-acetyl-glucosamine" type N-glycans, increased
      levels of alpha 2-6 sialylated N-glycans and "N,N'-diacetyl-lactosamine" type N
      glycans. These N-glycan changes were verified by examining gene transcript levels
      of the enzymes specific for their synthesis (MGAT3, ST6GAL1, and B4GALNT3) using
      qRT-PCR. We further evaluated the potential epigenetic influence on MGAT3
      expression by treating the cell lines with 5-azacytidine, a DNA methylation
      inhibitor. For the first time, we provide evidence that MGAT3 expression may be
      epigenetically regulated by DNA hypomethylation, leading to the synthesis of the
      unique "bisecting GlcNAc" type N-glycans on the membrane proteins of ovarian
      cancer cells. Linking the observation of specific N-glycan substructures and
      their complex association with epigenetic programming of their associated
      synthetic enzymes in ovarian cancer could potentially be used for the development
      of novel anti-glycan drug targets and clinical diagnostic tools. 

PMID- 24855065
TI  - Quantitative proteomic analysis of host-virus interactions reveals a role for
      Golgi brefeldin A resistance factor 1 (GBF1) in dengue infection.
AB  - Dengue virus is considered to be the most important mosquito-borne virus
      worldwide and poses formidable economic and health care burdens on many tropical
      and subtropical countries. Dengue infection induces drastic rearrangement of host
      endoplasmic reticulum membranes into complex membranous structures housing
      replication complexes; the contribution(s) of host proteins and pathways to this
      process is poorly understood but is likely to be mediated by protein-protein
      interactions. We have developed an approach for obtaining high confidence protein
      protein interaction data by employing affinity tags and quantitative proteomics,
      in the context of viral infection, followed by robust statistical analysis. Using
      this approach, we identified high confidence interactors of NS5, the viral
      polymerase, and NS3, the helicase/protease. Quantitative proteomics allowed us to
      exclude a large number of presumably nonspecific interactors from our data sets
      and imparted a high level of confidence to our resulting data sets. We identified
      53 host proteins reproducibly associated with NS5 and 41 with NS3, with 13 of
      these candidates present in both data sets. The host factors identified have
      diverse functions, including retrograde Golgi-to-endoplasmic reticulum transport,
      biosynthesis of long-chain fatty-acyl-coenzyme As, and in the unfolded protein
      response. We selected GBF1, a guanine nucleotide exchange factor responsible for
      ARF activation, from the NS5 data set for follow up and functional validation. We
      show that GBF1 plays a critical role early in dengue infection that is
      independent of its role in the maintenance of Golgi structure. Importantly, the
      approach described here can be applied to virtually any organism/system as a tool
      for better understanding its molecular interactions. 

PMID- 24855069
TI  - Membrane muscle function in the compliant wings of bats.
AB  - Unlike flapping birds and insects, bats possess membrane wings that are more
      similar to many gliding mammals. The vast majority of the wing is composed of a
      thin compliant skin membrane stretched between the limbs, hand, and body.
      Membrane wings are of particular interest because they may offer many advantages
      to micro air vehicles. One critical feature of membrane wings is that they camber
      passively in response to aerodynamic load, potentially allowing for simplified
      wing control. However, for maximum membrane wing performance, tuning of the
      membrane structure to aerodynamic conditions is necessary. Bats possess an array
      of muscles, the plagiopatagiales proprii, embedded within the wing membrane that
      could serve to tune membrane stiffness, or may have alternative functions. We
      recorded the electromyogram from the plagiopatagiales proprii muscles of Artibeus
      jamaicensis, the Jamaican fruit bat, in flight at two different speeds and found
      that these muscles were active during downstroke. For both low- and high-speed
      flight, muscle activity increased between late upstroke and early downstroke and
      decreased at late downstroke. Thus, the array of plagiopatagiales may provide a
      mechanism for bats to increase wing stiffness and thereby reduce passive membrane
      deformation. These muscles also activate in synchrony, presumably as a means to
      maximize force generation, because each muscle is small and, by estimation, weak.
      Small differences in activation timing were observed when comparing low- and high
      speed flight, which may indicate that bats modulate membrane stiffness
      differently depending on flight speed. 

PMID- 24855070
TI  - Are therapeutic motivation and having one's own doctor as researcher sources of
      therapeutic misconception?
AB  - BACKGROUND: Desire for improvement in one's illness and having one's own doctor
      functioning as a researcher are thought to promote therapeutic misconception
      (TM), a phenomenon in which research subjects are said to conflate research with
      treatment. PURPOSE: To examine whether subjects' therapeutic motivation and own
      doctor functioning as researcher are associated with TM. METHODS: We interviewed
      90 persons with advanced Parkinson's disease (PD) enrolled or intending to enrol
      in sham surgery controlled neurosurgical trials, using qualitative interviews.
      Subjects were compared by motivation (primarily therapeutic vs primarily
      altruistic or dually motivated by altruistic and therapeutic motivation), and by
      doctor status (own doctor as site investigator vs not) on the following:
      understanding of purpose of study; understanding of research procedures;
      perception of chance of direct benefit; and recollection and perceptions
      concerning the risks. RESULTS: 60% had primarily therapeutic motivation and 44%
      had their own doctor as the site investigator, but neither were generally
      associated with increased TM responses. Overall level of understanding of purpose
      and procedures of research were high. Subjects responded with generally high
      estimates of probability of direct benefit, but their rationales were personal
      and complex. The therapeutic-motivation group was more sensitive to risks. Five
      (5.6%) subjects provided incorrect answers to the question about purpose of
      research, and yet, showed excellent understanding of research procedures.
      CONCLUSIONS: In persons with PD involved in sham surgery clinical trials, being
      primarily motivated by desire for direct benefit to one's illness or having one's
      own doctor as the site investigator were not associated with greater TM
      responses.

PMID- 24855071
TI  - Molecular mechanisms of beta-lactam resistance in carbapenemase-producing
      Klebsiella pneumoniae from Sri Lanka.
AB  - Carbapenemases are increasingly important antimicrobial resistance determinants.
      Little is known about the carbapenem resistance mechanisms in Sri Lanka. We
      examined 22 carbapenem-resistant Klebsiella pneumoniae from Sri Lanka to
      determine their beta-lactam resistance mechanisms. The predominant resistance
      mechanisms we detected in this study were OXA-181, NDM-1 carbapenemases and
      extended-spectrum beta-lactamase CTX-M-15. All isolates were then genotyped by
      pulsed-field gel electrophoresis, variable-number tandem repeat sequence analysis
      and multilocus sequence typing, and seven distinct genotypes were observed. Five
      OXA-181-positive Klebsiella pneumoniae isolates were genotypically related to an
      isolate of Indian origin. Multilocus sequence typing found that these related
      isolates belong to ST-14, which has been associated with dissemination of OXA-181
      from the Indian subcontinent. Other genotypes we discovered were ST-147 and ST
      340, also associated with intercontinental spread of carbapenemases of suspected
      subcontinental origin. The major porin genes ompK35 and ompK36 from these
      isolates had insertions, deletions and substitutions. Some of these were
      exclusive to strains within single pulsotypes. We detected one ompK36 variant,
      ins AA134-135GD, in six ST-14- and six ST-147, blaOXA-181-positive isolates. This
      porin mutation was an independent predictor of high-level meropenem resistance in
      our entire Sri Lankan isolate collection (P=0.0030). Analysis of the Sri Lankan
      ST-14 and ST-147 ins AA134-135GD-positive isolates found ST-14 was more resistant
      to meropenem than other isolates (mean MIC: 32+/-0 ug ml(-1) and 20+/-9.47 ug ml(
      1), respectively, P=0.0277). The likely international transmission of these
      carbapenem resistance determinants highlights the need for regional collaboration
      and prospective surveillance of carbapenem-resistant Enterobacteriaceae.

PMID- 24855072
TI  - Giant ameloblastoma mortality; a consequence of ignorance, poverty and fear.
AB  - Ameloblastoma is a benign tumour of odontogenic origin. Although locally
      invasive, delay in treatment can lead to severe disfiguring of the facial region.
      In this report, we present two cases, a man and a woman, of a large ameloblastoma
      that presented with the typical radiographic features of variably sized
      radiolucent loculations. Patients presented initially with relatively small
      tumours but due to fear of surgery, ignorance and possibly poverty, tumour growth
      became enormous. The female patient died while awaiting consent for surgery and
      the male patient died at home due to complications closely associated with fear
      and growth of tumour. Literatures on mortality of ameloblastoma are reviewed. The
      need for more public enlightenment on the nature and treatment of facial tumours
      is highlighted. 

PMID- 24855073
TI  - An adult with a sinus venosus atrial septal defect and dilated cardiomyopathy.
AB  - Dilated cardiomyopathy, heart failure and atrial septal defects are well
      recognised entities in isolation, but are rarely seen together. Now that 90% of
      children with congenital heart disease survive into adulthood, such combinations
      of disease are increasingly seen in adult cardiology. While most young patients
      with dilated cardiomyopathy respond well to medical therapy, some do not, and
      require more invasive management. We describe a 32 year-old man with dilated
      cardiomyopathy and a sinus venosus-type atrial septal defect associated with a
      remarkable pulmonary to systemic flow ratio of 5:1. We propose that the atrial
      septal defect blunted his heart failure symptoms by serving as a 'pop-off' valve
      and limiting pulmonary congestion. The patient ultimately failed medical
      management and received a left ventricular assist device. The case is presented
      along with a discussion of this unique pathophysiology and a brief review of the
      literature in this rapidly evolving field. 

PMID- 24855074
TI  - Posterior reversible leukoencephalopathy syndrome as a presenting manifestation
      of p-ANCA-associated vasculitis.
AB  - Rapidly progressing glomerulonephritis like microscopic polyangiitis and allergic
      granulomatous angiitis are among the common presentations of perinuclear
      antineutrophilic cytoplasmic antibody (p-ANCA) vasculitis. Involvement of central
      nervous system is rare in contrast to mononeuritis multiplex, which is a well
      known neurological manifestation of this condition. We report a case presented
      with uraemic encephalopathy and posterior reversible encephalopathy syndrome
      (PRES)-related symptoms, which showed recovery after haemodialysis although PRES
      with seizures recurred later. As uraemic encephalopathy appears to be the
      underlying aetiology as per the temporal correlation of correction of uraemia and
      resolution of the symptoms of PRES, it becomes a rare case of uraemia-induced
      PRES as a presenting manifestation of p-ANCA-associated vasculitis along with
      necrotising crescentic glomerulonephritis. 

PMID- 24855075
TI  - Subclavian vein thrombosis in an otherwise healthy 9-year-old boy.
AB  - We report a previously well 9-year-old boy who presented with an acutely swollen
      left arm after horse riding. Left subclavian vein thrombosis was demonstrated by
      MR venography but there was no evidence of an underlying anatomical abnormality.
      The child was successfully treated with catheter directed thrombolysis and
      anticoagulation with intravenous unfractionated heparin and warfarin. We have
      identified 75 previously published case reports of effort-induced upper extremity
      deep vein thrombosis (UEDVT) and surveyed patient characteristics and
      precipitating activities. In this case and literature review, we demonstrate that
      individuals with effort-induced UEDVT show demographic characteristics and
      presenting features that are distinct from other patient groups with venous
      thromboembolic disease. We also highlight the difficulties in counselling
      affected individuals about modifying occupational and recreational activities to
      minimise the risk of recurrent thrombosis. 

PMID- 24855076
TI  - Acromioclavicular joint dislocation with associated brachial plexus injury.
AB  - We present the case of a 32-year-old female who sustained a left
      acromioclavicular (AC) joint type V injury and brachial plexus injury. The
      patient's AC joint injury was identified 6 days after she was involved in a
      motorbike accident where she sustained multiple other injuries. She required
      operative fixation of the AC joint using a locking compression medial proximal
      tibial plate. At 3 months post operatively, the patient was found to have a
      subluxed left shoulder as a result of an axonal injury to the upper trunk of the
      brachial plexus. In addition, the tibial plate had cut out. The plate was
      subsequently removed. At 8 months the glenohumeral articulation had been restored
      and the patient had clinically regained significant shoulder function. After 15
      months the patient was pain free and could complete all her activities of daily
      living without impediment. She returned to playing competitive pool after 24
      months. 

PMID- 24855077
TI  - The importance of timely detection and management in neonatal appendicitis.
AB  - The clinical presentation of cute appendicitis is rarely encountered in
      neonatology. When it does occur, it is thought to be due to prematurity or
      develops secondary to coexisting diseases. We present a case of appendicitis in a
      10-day-old Middle-Eastern girl, who was born at term and who had no underlying
      conditions that are typically associated with neonatal appendicitis. This case
      highlights that certain causes and clinical signs are unreliable when coming to a
      working diagnosis of neonatal appendicitis, and that regardless of the cause,
      timely detection and management are necessary in achieving surgical success. 

PMID- 24855078
TI  - Prolapsed giant sigmoid lipoma: a rare cause of adult ischaemic intussusception.
AB  - Intussusception is a rare cause of obstruction in adults and has a variable, non
      specific presentation. Adult intussusception is usually associated with an
      underlying organic pathology, such as a benign or malignant tumour which acts as
      the lead point. Prolapse of the lead-point mass through the anal canal is an
      extremely rare presentation with very few reported cases in the literature. We
      describe a case of a 67-year-old man who presented with rectal prolapse of a
      large soft tissue mass. CT of the abdomen and barium enema revealed partial
      intussusception of an upper sigmoid lipomatous polyp. Examination under
      anaesthesia was performed and the prolapse reduced. A laparoscopic sigmoid
      colectomy was planned. The patient subsequently re-presented clinically unwell
      with a recurrent necrotic prolapsing mass. Laparotomy and sigmoid colectomy was
      performed and the patient recovered fully. The resected mass was a 7*4.5*4.0 cm
      necrotic sigmoid lipoma. 

PMID- 24855079
TI  - Bilateral diffuse uveal melanocytic proliferation: a management dilemma.
AB  - A female patient suffered from gradual decline of vision for few months. She
      presented with bilateral multiple pigmented choroidal tumours, associated with
      overlying retinal changes. The clinical presentation suggested bilateral diffuse
      uveal melanocytic proliferation (BDUMP) syndrome, which is a paraneoplastic
      disease, although there was no evidence of any concurrent malignancy. The
      periodic systemic surveillance that was undertaken for the following 4 years
      failed to reveal any occult cancer. Nevertheless, there has been relentless
      progressive deterioration in vision as a consequence of BDUMP syndrome. The
      management of the declining vision in BDUMP syndrome is challenging and
      controversial. 

PMID- 24855081
TI  - Resolving back pain: a case of untreated discitis.

PMID- 24855080
TI  - Sepsis-related hypertensive response: friend or foe?
AB  - In daily practice acute arterial hypertension may occur during acute sepsis. No
      management guidelines concerning this issue figured in the latest sepsis campaign
      guidelines. Arterial hypertension occurring during sepsis could be an overlooked
      condition despite its potential haemodynamic harmful consequences. In this paper,
      a clinical study of acute hypertensive response related to sepsis is detailed. It
      shows that arterial hypertension, renal salt wasting and glomerular
      hyperfiltration can occur simultaneously during sepsis. Mechanisms and management
      options of sepsis-related arterial hypertensive response are also discussed. 

PMID- 24855082
TI  - A weeping umbilical hernia: bilateral ovarian mucinous cystadenoma with
      disseminated peritoneal adenomucinosis.
AB  - A young woman was referred to us for the management of an umbilical hernia with
      macerated overlying skin through which massive ascites was leaking. On
      examination we found a jelly-like substance seeping out of the opening. A
      contrast-enhanced CT scan of the abdomen revealed bilateral ovarian
      cystadenocarcinoma with pseudomyxoma peritonei. The patient underwent
      cytoreductive surgery along with hysterectomy and bilateral oophorectomy followed
      by hyperthermic intraperitoneal chemotherapy with mitomycin C. Histopathological
      examination showed bilateral borderline cystadenoma with peritoneal
      adenomucinosis. Follow-up at 1 year showed no signs of recurrence. 

PMID- 24855083
TI  - Ulcerative colitis-induced myocarditis.

PMID- 24855085
TI  - Paraspinal extraskeletal Ewing's sarcoma: a rare clinical entity.

PMID- 24855084
TI  - Intravesical foreign body: clinical features and diagnostic clues.

PMID- 24855086
TI  - A case of cutaneous sterile pyogranuloma/granuloma syndrome in a maltese.
AB  - Cutaneous sterile pyogranuloma/granuloma syndrome (SPGS) is a locally restricted
      multinodular dermatitis. Affected dogs are typically healthy, but a few show
      systemic signs. Herein, a case of a dog presenting with generalized ulcerative
      dermatitis with systemic signs of mild anemia and an increased C-reactive protein
      level is described. Cutaneous SPGS was diagnosed by histopathology, negative
      staining causative organisms, and polymerase chain reaction for Mycobacterium
      spp. Successful treatment was achieved by immunosuppressive drugs, including
      prednisolone and azathioprine, administered for at least 20 mo. Recurrences of
      skin lesions were observed when prednisolone and/or azathioprine were
      discontinued. Long-term management with immunosuppressive agents may be required
      if the affected dog exhibits severe symptoms of cutaneous SPGS. 

PMID- 24855087
TI  - Evaluation of data from 35 dogs pertaining to dehiscence following intestinal
      resection and anastomosis.
AB  - The objectives of this study were to evaluate blood and abdominal fluid lactate
      and glucose, fluid cytology, culture, and volume 24 and 48 hr following
      intestinal resection and anastomosis in dogs with and without closed-suction
      drains and to correlate findings with survival. Thirty-five client-owned dogs
      that underwent intestinal resection and anastomosis were prospectively enrolled
      in the study. Abdominal fluid was submitted for culture at surgery and again 24
      hr postoperatively. Twenty-four and 48 hr postoperatively, blood and abdominal
      fluid glucose and lactate were measured and fluid was submitted for cytology.
      Abdominal fluid was collected either from a closed-suction drain or by
      abdominocentesis. Patients were followed either for 14 days or until death.
      Comparisons were made based on development of dehiscence and presence or absence
      of a drain. Patients with dehiscence were more likely to have positive cultures
      at 24 hr and to have had more bowel resected. Surviving patients without drains
      had significantly smaller differences in blood and fluid glucose and lactate both
      24 and 48 hr postoperatively than surviving patients with drains. The significant
      differences identified between patients with and without drains suggests a need
      for further research into the effect of drains on abdominal fluid values. 

PMID- 24855088
TI  - Tracheal foreign body and pneumonia in a cat: a near missed diagnosis.
AB  - A 12 yr old mixed-breed Maine coon was referred with a 1 wk history of
      intermittent respiratory distress. Physical examination and thoracic radiograph
      abnormalities were consistent with bronchopneumonia and chronic feline asthma.
      Repeat thoracic radiographs and lung aspirate cytology supported those diagnoses.
      Response to treatment was incomplete. One wk later, due to a change in
      respiratory pattern, cervical radiographs were obtained. A soft-tissue density
      was apparent in the cat's cervical trachea. Bronchoscopy was performed and a
      segment of a pine cone was removed from the cat's trachea. Following removal of
      the foreign body, the cat's respiratory signs resolved. Premature diagnostic
      closure may prevent a clinician from recognizing an underlying missed diagnosis
      when response to treatment does not occur as expected. 

PMID- 24855089
TI  - Presumptive subdural empyema in a dog.
AB  - A 13 mo old mixed-breed dog was referred for acute lateralized forebrain signs.
      MRI of the brain demonstrated abnormalities consistent with severe meningitis and
      subdural empyema secondary to a retrobulbar abscess. The dog's clinical signs
      improved with antibiotic therapy, and repeat imaging showed resolution of
      subdural fluid accumulation presumed to be empyema with mild residual meningeal
      enhancement. Subdural empyema is an infrequent cause of encephalopathy in small
      animals and usually develops through direct extension of a pericranial infection.
      This report presents a case of presumptive subdural empyema in a dog that was
      successfully treated without surgical intervention. MRI is the preferred imaging
      modality for diagnosis of subdural empyema, and the characteristic imaging
      features are described. 

PMID- 24855090
TI  - Owner experiences in treating dogs and cats diagnosed with diabetes mellitus in
      the United States.
AB  - The objective of this study was to report owner experiences and satisfaction in
      treating a pet with diabetes mellitus using a descriptive report from an Internet
      based survey. Descriptive analysis of results was performed, chi(2) tests were
      used to detect differences in responses between dog and cat owners, and
      correlations were assessed using the nonparametric Spearman rank correlation. A
      total of 834 owners participated in the survey. More diabetic dogs (97%) than
      cats (82%) were treated with insulin injections. Insulin was administered twice
      daily in 87% of dogs and 73% of cats. Porcine lente and neutral protamine
      Hagedorn were the most commonly administered insulins in dogs. In cats, glargine
      and protamine zinc insulin were the most commonly used insulins. Most pets were
      not fed a prescribed diabetes diet. More cat (66%) than dog (50%) owners were
      satisfied with the diabetic control achieved. Cat owners were more likely to use
      home blood glucose monitoring. Treatment was considered expensive by the majority
      of owners. Few published reports follow diabetic pets after diagnosis or report
      owner satisfaction. The results of this study provide useful information that may
      help veterinarians better educate owners and set expectations regarding diabetes
      treatment and quality of life for diabetic pets. 

PMID- 24855091
TI  - Reputation management on facebook: awareness is key to protecting yourself, your
      practice, and the veterinary profession.
AB  - From the Social media use by health professionals occurs in a digital environment
      where etiquette has yet to be solidly defined. The objectives of this study were
      to explore veterinarians' personal use of Facebook, knowledge of privacy
      settings, and factors related to sharing personal information online. All
      American Animal Hospital Association member veterinarians with a valid e-mail
      address (9469) were invited to complete an online survey about Facebook (e.g.,
      time spent on Facebook, awareness of consequences, types of information posted).
      Questions assessing personality dimensions including trust, popularity, self
      esteem and professional identity were included. The response rate was 17% (1594
      of 9469); 72% of respondents (1148 of 1594) had a personal Facebook profile.
      Veterinarians were more likely to share information on Facebook than they would
      in general. Trust, need for popularity, and more time spent on Facebook predicted
      more disclosure of personal information on Facebook. Awareness of consequences
      and increased veterinary experience predicted lesser disclosure. As veterinary
      practices use Facebook to improve client services, they need also to manage risks
      associated with online disclosure by staff. Raising awareness of reputation
      management and consequences of posting certain types of information to Facebook
      is integral to protecting the individual, the practice, and the veterinary
      profession. 

PMID- 24855093
TI  - Computed tomographic features of pneumothorax secondary to a bronchopleural
      fistula in two dogs.
AB  - A bronchopleural fistula (BPF) can lead to continuous pneumothorax and is rarely
      reported clinically in dogs. This report describes computed tomographic (CT)
      findings in two dogs with BPFs and subsequent continuous pneumothoraces that
      necessitated thoracotomy. Both dogs had a peripheral BPF in the right caudal lung
      lobe. The fistula in one dog was secondary to a previous foreign body migration,
      and the fistula in the other was thought to be secondary to dirofilariasis. On
      both CT examinations, a dilated subsegmental bronchus was seen communicating with
      the pleural space at the center of a focal, concave region of parenchymal
      consolidation. Multiplanar reformatting aided in identification and
      characterization of the BPF. The pneumothoraces resolved after right caudal
      lobectomy in both dogs. CT has the potential to identify BPFs, such as secondary
      to foreign body migration or dirofilariasis. 

PMID- 24855092
TI  - Inside the brachycephalic nose: conchal regrowth and mucosal contact points after
      laser-assisted turbinectomy.
AB  - This prospective observational study analyzed conchal regrowth after laser
      assisted turbinectomy (LATE) in brachycephalic dogs and the mucosal contact of
      regrown conchae. Eighty brachycephalic dogs (41 pugs, 39 French bulldogs [FBs])
      that underwent LATE because of obstructing conchae were evaluated by endoscopy 7
      days and 6 mo after surgery. At 6 mo, 96% of FBs' and 65% of pugs' nasal cavities
      showed regrowth of turbinates. FBs showed higher growth grades than pugs.
      Revision surgery because of reobstructing regrowth was required in the nasal
      cavities of 17% of FBs and 3% of pugs. The mean number of contact points reduced
      from 3.0 in FB and 1.7 in pugs before surgery to 1.2 in FB and 0.2 in pugs after
      conchal regrowth. Recollapse of nares after surgery significantly influenced the
      frequency of reoccurrence of contact points. LATE was proven to be an effective
      treatment of intranasal obstruction caused by mucosal contact between conchae.
      Conchal regrowth commonly occurs after surgical removal, but the new conchae
      cause less obstruction due to a significant reduction in number of contact
      points. Revision surgery because of reobstruction is rarely necessary. The
      important physiologic functions of conchae make nonobstructing regrowth
      desirable. 

PMID- 24855094
TI  - Outcome of 45 dogs with laryngeal paralysis treated by unilateral arytenoid
      lateralization or bilateral ventriculocordectomy.
AB  - The purpose of this retrospective study was to assess risk factors and
      complications affecting postoperative outcome of dogs with laryngeal paralysis
      treated by either unilateral arytenoid lateralization (UAL) or bilateral
      ventriculocordectomy (VCC). Medical records of all dogs having either UAL or VCC
      between 2000 and 2011 were analyzed. Twenty-five dogs had VCC and 20 dogs had
      UAL. The overall postoperative complications rates for VCC and UAL were similar
      (52% and 60%, respectively; P = .0887). Dogs that had UAL were more likely to
      have acute postoperative respiratory distress and aspiration pneumonia (P =
      .0526). Dogs with VCC were more likely to have chronic postoperative respiratory
      distress and aspiration pneumonia (P = .0079). Revision surgery was required in 6
      dogs (24%) following VCC and 2 dogs (10%) following UAL. Sex, breed, presenting
      complaint, type of service provided, and concurrent diseases were not
      significantly associated with higher risk of either death or decreased survival
      time postoperatively with either procedure. Overall postoperative complication
      rates, required revision surgeries, and episodes of aspiration pneumonia were
      similar in dogs undergoing UAL and VCC surgeries. Dogs that had VCC appeared to
      have an increased risk of lifelong complications postoperatively compared with
      UAL; therefore, VCC may not be the optimal choice for treatment of laryngeal
      paralysis. 

PMID- 24855096
TI  - An adult patient with common B-cell acute lymphoblastic leukaemia who presented
      with pancreatic involvement, description of the second adult case and review of
      paediatric cases.
AB  - Pancreatic involvement in acute lymphoblastic leukaemia (ALL) may go
      unrecognised. There are only a few paediatric cases; nevertheless, presentation
      with pancreatic involvement in an adult patient with ALL has been reported
      rarely. Our 52-year-old male patient came to us with abdominal pain, nausea and
      vomiting; he had pancreatic enlargement on CT. He was diagnosed with common B
      cell ALL with pancreatic involvement. The patient obtained haematological
      remission and the pancreatic enlargement regressed after chemotherapy, but later
      he had central nervous system and liver relapses. He died 6 months after
      diagnosis because of progressive pneumonia and chemotherapy-resistant ALL with
      multiple extramedullary relapses.

PMID- 24855097
TI  - Successful treatment of phantom limb pain and phantom limb sensation in the
      traumatic amputee using scalp acupuncture.

PMID- 24855098
TI  - Hookah smoking in high school students and its determinants in Iran: a
      longitudinal study.
AB  - Hookah smoking has increased worldwide, especially among youth, and has been
      identified as an emerging threat to public health. The aim of the present study
      was to estimate the prevalence and transition rates in hookah smoking statuses
      and predictors of transitions among a representative sample of Iranian high
      school students. In this longitudinal study, a representative sample (n = 5197)
      of students in the northwest of Iran was assessed thrice with a 6-month interval
      in 2010 and 2011. A self-administered questionnaire was used to measure hookah
      smoking, demographic characteristics, and personal and environmental factors. In
      total, the prevalence of hookah use (at least once a month) in this study was
      6.0% (95% confidence interval [CI] = 5.1, 6.9). Results indicated that 44.9% (95%
      CI = 43.0, 46.7) of the students in the sample at least tried hookah smoking.
      During 1 year, 18.5% and 1.5% of students who have never used hookah before had
      transitioned to experimenter and regular hookah smoking, respectively, and
      notably, 7.8% of experimenters had transitioned to regular hookah smoking.
      Adjusted for other factors, being male, regular cigarette smoking, and positive
      attitude toward smoking were factors associated with students' transition to
      hookah smoking status. The incidence rate of hookah smoking in adolescents is
      notable. The findings identified the co-occurrence of risky behaviors that
      support programs aimed at reducing or preventing high-risk behaviors
      simultaneously. 

PMID- 24855099
TI  - Use of multiple imputation to correct for bias in lung cancer incidence trends by
      histologic subtype.
AB  - BACKGROUND: Over the past several decades, advances in lung cancer research and
      practice have led to refinements of histologic diagnosis of lung cancer. The
      differential use and subsequent alterations of nonspecific morphology codes,
      however, may have caused artifactual fluctuations in the incidence rates for
      histologic subtypes, thus biasing temporal trends. METHODS: We developed a
      multiple imputation (MI) method to correct lung cancer incidence for nonspecific
      histology using data from the Surveillance, Epidemiology, and End Results Program
      during 1975 to 2010. RESULTS: For adenocarcinoma in men and squamous in both
      genders, the change to an increasing trend around 2005, after more than 10 years
      of decreasing incidence, is apparently an artifact of the changes in
      histopathology practice and coding system. After imputation, the rates remained
      decreasing for adenocarcinoma and squamous in men, and became constant for
      squamous in women. CONCLUSIONS: As molecular features of distinct histologies are
      increasingly identified by new technologies, accurate histologic distinctions are
      becoming increasingly relevant to more effective "targeted" therapies, and
      therefore, are important to track in patients. However, without incorporating the
      coding changes, the incidence trends estimated for histologic subtypes could be
      misleading. IMPACT: The MI approach provides a valuable tool for bridging the
      different histology definitions, thus permitting meaningful inferences about the
      long-term trends of lung cancer by histologic subtype.

PMID- 24855100
TI  - HIF1 activity in granulosa cells is required for FSH-regulated Vegfa expression
      and follicle survival in mice.
AB  - Recent evidence has suggested that vascular endothelial growth factor A (VEGFA)
      is an important regulator of ovarian follicle development and survival. Both LH
      and FSH regulate Vegfa expression in granulosa cells and signal via the
      transcription factor hypoxia inducible factor 1 (HIF1). To further study the
      mechanism of action of HIF1 in the regulation of Vegfa, we studied
      Vegfa(delta/delta) mice, which lack a hypoxia response element in the Vegfa
      promoter. Granulosa cells from Vegfa(delta/delta) mice failed to respond to FSH
      or LH with an increase in Vegfa mRNA expression in vitro, and granulosa cells
      isolated from eCG-treated immature Vegfa(delta/delta) mice had significantly
      lower Vegfa mRNA levels compared to controls. However, normal Vegfa mRNA levels
      were detected in the granulosa cells from immature Vegfa(delta/delta) mice
      following hCG treatment. Vegfa(delta/delta) females produced infrequent litters,
      and their pups died shortly after birth. Ovaries from Vegfa(delta/delta) mice
      were much smaller than controls and contained few antral follicles and corpora
      lutea. Antral follicles numbers were decreased by nearly 50% in ovaries from
      Vegfa(delta/delta) mice relative to controls, and 74% of antral follicles in
      Vegfa(delta/delta) ovaries were atretic. Serum progesterone levels in adult
      Vegfa(delta/delta) females were significantly lower, apparently reflecting
      reduced numbers of corpora lutea. This study demonstrates for the first time the
      requirement of HIF1 for FSH-regulated Vegfa expression in vivo and that HIF1 acts
      via a single hypoxia response element in the Vegfa promoter to exert its
      regulatory functions. Our findings also further define the physiological role of
      VEGFA in follicle development. 

PMID- 24855101
TI  - Impaired placental vasculogenesis compromises the growth of sheep embryos
      developed in vitro.
AB  - To evaluate how assisted reproductive technologies (ART) affect vasculogenesis of
      the developing conceptus, we analyzed placental and fetal development of in vitro
      produced (IVP) sheep embryos. Pregnancies produced by ART carry increased risk of
      low birth weight, though what causes this risk remains largely unknown. We
      recently reported that developmental arrest of sheep conceptuses obtained by ART
      is most pronounced when the cardiovascular system develops (Days 20-30 of
      development). A total of 86 IVP blastocysts (2-4 per ewe) were surgically
      transferred to 30 recipient sheep 6 days after estrus; 20 sheep were naturally
      mated (control). Conceptuses were recovered from sheep at Days 20, 22, 26, and 30
      of gestation and morphologically evaluated. Then, the conceptuses and part of
      their placentae (chorion-allantois) were fixed for histological and
      immunohistochemical analysis and snap-frozen in liquid nitrogen for subsequent
      mRNA expression analysis. Results demonstrate that the cardiovascular systems of
      sheep IVP conceptuses were severely underdeveloped. Pericardial and placental
      hemorrhages were noted in a majority (5/7) of the dead embryos. In the surviving
      IVP embryos, the expression of angiogenetic factors was reduced at Day 20. The
      placental vessels were underdeveloped on Days 20 and 22 (P < 0.05), though
      placental vasculogenesis was successfully completed on subsequent days. However,
      low vessel number persisted at Days 26 and 30 (4.6 vs. 5.9 and 6.64 vs. 8.70 per
      field, respectively; P < 0.05) together with reduced vessel diameter at Day 26
      (46.89 vs. 89.92 MUm; P < 0.05). In vitro production of sheep embryos induced
      severely impaired vasculogenesis early in gestation. This may lead to
      developmental programing problems, such as intrauterine growth restriction of the
      fetus, resulting in long-term health consequences for the offspring, such as
      cardiovascular diseases. 

PMID- 24855102
TI  - Galectin-3 contributes to luteolysis by binding to Beta 1 integrin in the bovine
      corpus luteum.
AB  - Luteolysis is characterized by a reduction in progesterone (P4) production and
      tissue degeneration in the corpus luteum (CL). One of major events during
      luteolysis is luteal cell death. Galectin-3, a ubiquitously expressed protein
      involved in many cellular processes, serves as an antiapoptotic and/or
      proapoptotic factor in various cell types. Although galectin-3 is detected in the
      bovine CL, its role remains unclear. The expression of galectin-3 in the bovine
      CL was higher at the regressed stage than at the other luteal stages. Galectin-3
      was localized on luteal steroidogenic cells (LSCs). When cultured LSCs were
      exposed to prostaglandin F2alpha (PGF) for 48 h, the expression and secretion of
      galectin-3 increased. When the cultured LSCs were treated with galectin-3 for 24
      h, cleaved caspase-3 expression was increased, and the cell viability was
      decreased, whereas P4 production did not change. Beta 1 integrin, a target
      protein of galectin-3, was expressed in bovine CL and possessed glycans, which
      galectin-3 binds. Furthermore, galectin-3 bound to glycans of luteal beta 1
      integrin. The decreased cell viability of cultured LSCs by galectin-3 was
      suppressed by beta 1 integrin antibody. The overall findings suggest that the
      secreted galectin-3 stimulated by PGF plays a role in structural luteolysis by
      binding to beta 1 integrin. 

PMID- 24855103
TI  - Preimplantation mouse embryo is a target for opioid ligand-receptor signaling.
AB  - Synchronization of preimplantation embryo development to blastocysts is one of
      the prerequisites for normal embryo implantation. While previous studies have
      ascribed an adverse effect to aberrant opioid signaling on embryo and fetal
      development, it has remained unclear whether the opioid system is operative in
      early pregnancy events. In the present study, employing multiple pharmacological
      and genetic approaches, we demonstrated that preimplantation embryos spanning the
      zygote to blastocyst express the opioid receptor subtypes and the oviduct
      expresses endogenous opioid precursors dynamically, which suggest that opioid
      signaling is functionally operative during preimplantation embryo development.
      Subsequent analysis further revealed that an aberrantly activated opioid
      signaling by morphine can remarkably derail normal preimplantation embryo
      development via inhibiting intracellular calcium mobilization, while a
      cotreatment of naloxone with morphine can remarkably reverse the adverse effects
      of morphine on preimplantation embryo development. Besides shedding light on the
      pathophysiological significance of the opioid system during early embryo
      development in mice, our findings have potential clinical relevance because an
      abused use of illicit opiate drugs is frequently associated with retarded fetal
      development and pregnancy failure in women. 

PMID- 24855105
TI  - Fertilization-induced autophagy in mouse embryos is independent of mTORC1.
AB  - Autophagy is a dynamically regulated intracellular degradation system that is
      important for cellular processes such as amino acid production during starvation
      and intracellular quality control. Previously, we reported that autophagy is
      suppressed in oocytes but is rapidly up-regulated after fertilization. During
      this period, autophagy is thought to be important for the generation of amino
      acids from the bulk degradation of maternal proteins that have accumulated during
      oogenesis. However, the mechanism of autophagy induction after fertilization is
      presently unknown. In most cell types, autophagy is negatively controlled by
      mammalian target of rapamycin complex 1 (mTORC1), which is typically regulated by
      amino acids and insulin or related growth factors. In this study, we determined
      the role of mTORC1 in fertilization-induced autophagy. On the basis of the
      phosphorylation status of mTORC1 substrates, we found that mTORC1 activity was
      relatively high in metaphase II (MII) oocytes but was rapidly decreased within 3
      h of fertilization. However, chemical inhibition of mTORC1 by Torin1 or PP242 in
      MII oocytes or fertilized embryos did not induce autophagy. In addition,
      activation of mTORC1 by cycloheximide did not inhibit fertilization-induced
      autophagy in fertilized embryos. By contrast, the phosphatidylinositol 3-kinase
      inhibitors wortmannin and LY294002 effectively suppressed autophagy in these
      embryos. These data suggest that, even though autophagy induction and
      postfertilization mTORC1 activity are inversely correlated with each other, as
      observed in other cell types, mTORC1 suppression is neither essential nor
      sufficient for fertilization-induced autophagy, highlighting a unique feature of
      the regulation mechanism of autophagy-mediated intracellular turnover in early
      embryos. 

PMID- 24855104
TI  - Gestational exposure to elevated testosterone levels induces hypertension via
      heightened vascular angiotensin II type 1 receptor signaling in rats.
AB  - Pre-eclampsia is a life-threatening pregnancy disorder whose pathogenesis remains
      unclear. Plasma testosterone levels are elevated in pregnant women with pre
      eclampsia and polycystic ovary syndrome, who often develop gestational
      hypertension. We tested the hypothesis that increased gestational testosterone
      levels induce hypertension via heightened angiotensin II signaling. Pregnant
      Sprague-Dawley rats were injected with vehicle or testosterone propionate from
      Gestational Day 15 to 19 to induce a 2-fold increase in plasma testosterone
      levels, similar to levels observed in clinical conditions like pre-eclampsia. A
      subset of rats in these two groups was given losartan, an angiotensin II type 1
      receptor antagonist by gavage during the course of testosterone exposure. Blood
      pressure levels were assessed through a carotid arterial catheter and endothelium
      independent vascular reactivity through wire myography. Angiotensin II levels in
      plasma and angiotensin II type 1 receptor expression in mesenteric arteries were
      also examined. Blood pressure levels were significantly higher on Gestational Day
      20 in testosterone-treated dams than in controls. Treatment with losartan during
      the course of testosterone exposure significantly attenuated testosterone-induced
      hypertension. Plasma angiotensin II levels were not significantly different
      between control and testosterone-treated rats; however, elevated testosterone
      levels significantly increased angiotensin II type 1 receptor protein levels in
      the mesenteric arteries. In testosterone-treated rats, mesenteric artery
      contractile responses to angiotensin II were significantly greater, whereas
      contractile responses to K(+) depolarization and phenylephrine were unaffected.
      The results demonstrate that elevated testosterone during gestation induces
      hypertension in pregnant rats via heightened angiotensin II type 1 receptor
      mediated signaling, providing a molecular mechanism linking elevated maternal
      testosterone levels with gestational hypertension. 

PMID- 24855107
TI  - MicroRNA-31 is significantly elevated in both human endometrium and serum during
      the window of implantation: a potential biomarker for optimum receptivity.
AB  - The window of implantation of human embryos into the endometrium spans Cycle Days
      20-24 of the 28-day menstrual cycle. However, uterine receptivity may not be
      reliably replicated in infertile patients throughout this span. Thus, it is of
      importance to be able to determine optimal receptivity through a minimally
      invasive measure. We screened expression of a number of candidate micro-RNAs
      (miRNAs) in endometrial tissues and serum collected from a panel of fertile women
      during both the proliferative phase and the secretory phase of a normal menstrual
      cycle. We found that several miRNAs were significantly elevated in endometrial
      tissues in the secretory phase versus the proliferative phase. One of these, miR
      31, was found to be not only detectable in serum samples but also significantly
      elevated in the secretory phase versus the proliferative phase. MiR-31 is known
      to target several immunomodulatory factors, such as FOXP3 and CXCL12. We find
      that both of these factors are significantly downregulated in endometrial tissues
      during the secretory phase. Our data suggest that miR-31 is a potential biomarker
      for optimal endometrial receptivity, possibly operating through an
      immunosuppressive mechanism. 

PMID- 24855106
TI  - The SMC5/6 complex is involved in crucial processes during human spermatogenesis.
AB  - Genome integrity is crucial for safe reproduction. Therefore, chromatin structure
      and dynamics should be tightly regulated during germ cell development. Chromatin
      structure and function are in large part determined by the structural maintenance
      of chromosomes (SMC) protein complexes, of which SMC5/6 recently has been shown
      to be involved in both spermatogonial differentiation and meiosis during mouse
      spermatogenesis. We therefore investigated the role of this complex in human
      spermatogenesis. We found SMC6 to be expressed in the human testis and present in
      a subset of type Adark and type Apale spermatogonia, all spermatocytes, and round
      spermatids. During human meiosis, SMC5/6 is located at the synaptonemal complex
      (SC), the XY body, and at the centromeres during meiotic metaphases. However, in
      contrast to mouse spermatogenesis, SMC6 is not located at pericentromeric
      heterochromatin in human spermatogenic cells, indicating subtle but perhaps
      important differences in not only SMC5/6 function but maybe also in maintenance
      of genomic integrity at the repetitive pericentromeric regions. Nonetheless, our
      data clearly indicate that the SMC5/6 complex, as shown in mice, is involved in
      numerous crucial processes during human spermatogenesis, such as in
      spermatogonial development, on the SC between synapsed chromosomes, and in DNA
      double-strand break repair on unsynapsed chromosomes during pachynema. 

PMID- 24855108
TI  - An efficient system to establish biopsy-derived trophoblastic cell lines from
      bovine embryos.
AB  - Trophoblastic cells play a crucial role in implantation and placentogenesis and
      can be used as a model to provide substantial information on the peri
      implantation period. Unfortunately, there are few cell lines for this purpose in
      cattle because of the difficulty of raising successive cell stocks in the long
      term. Our results show that the combination of a monolayer culture system in
      microdrops on a surface treated with gelatin and the employment of conditioned
      media from mouse embryonic fibroblasts support the growth of bovine trophoblastic
      cells lines from an embryo biopsy. Expression profiles of mononucleate- and
      binucleate-specific genes in established trophoblastic cells lines represented
      various stages of gestation. Moreover, the ability to expand trophoblastic cell
      lines for more than 2 yr together with pluripotency-related gene expression
      patterns revealed certain self-renewal capacity. In summary, we have developed a
      system to expand in vitro trophoblastic cells from an embryo biopsy that solves
      the limitations of using amplified DNA from a small number of cells for bovine
      embryo genotyping and epigenotyping and, on the other hand, facilitates the
      establishment of trophoblastic cell lines that can be useful as peri-implantation
      in vitro models. 

PMID- 24855110
TI  - Should we bother with second-hand smoke exposure if smoking is on track? A poorly
      explored discrepancy in Denmark.
AB  - The recognition of the serious health-damaging effects of tobacco smoke exposure
      has initiated several preventive programmes on the national and international
      levels worldwide. In the last decade, a considerable decrease in the prevalence
      of active smoking was observed in Denmark, changing the country from a poor to a
      favourable position in comparison to other EU countries. However, second-hand
      tobacco smoke exposure, especially in homes, still ranks Denmark among the
      problematic countries in Europe. This poorly recognised and studied discrepancy
      calls for further research and effective targeted interventions on population
      level. 

PMID- 24855109
TI  - Peptides in seminal fluid and their role in infertility: a potential role for
      opiorphin inhibition of neutral endopeptidase activity as a clinically relevant
      modulator of sperm motility: a review.
AB  - Infertility is a devastating medical condition that adversely affects emotional
      health and well-being of couples who desire pregnancy and parenthood. The overall
      demographic data suggest that the indication for more than one-third of assisted
      reproductive technology cycles performed in the United States includes male
      factor infertility. There is increasing recognition of the role that peptides
      present in seminal plasma have in determining sperm motility. Several recent
      studies suggest that peptidases, such as neutral endopeptidase (NEP) and
      aminopeptidase N (APN), impose significant adverse effects on sperm motility.
      Interestingly, several recent studies demonstrate that there is an endogenous
      NEP/APN inhibitor peptide called opiorphin in human seminal plasma. Our pilot
      studies suggest opiorphin promotes sperm motility and may positively influence
      sperm motility parameters in some cases of males infertility characterized by
      asthenozoospermia. 

PMID- 24855112
TI  - Association of chylothorax and direct pleura involvement in a case of
      Waldenstrom's macroglobulinaemia.
AB  - An 82-year-old male was hospitalised for dyspnoea, hypoxaemia and general
      fatigue; a predominant left chylothorax was revealed. Previously, he had been
      diagnosed with Waldenstrom's macroglobulinaemia (WM). Chylothorax complications
      in patients with WM are rare events and only six such cases have so far been
      reported. The most common malignant causes of chylothorax are through mediastinal
      adenopathy. Direct infiltration of the pleura by tumour cells is the most likely
      cause with this patient, and for this reason, we believe that this case is an
      instructive one. Chemotherapy induced rapid and persistent improvement after 10
      month follow-up. 

PMID- 24855111
TI  - Current prevalence of dementia, depression and behavioural problems in the older
      adult care home sector: the South East London Care Home Survey.
AB  - BACKGROUND: a large and increasing number of older people in the UK are living in
      care homes. Dementia is a frequent reason underlying admission and determining
      care needs, but prevalence data are becoming increasingly outdated and reliant on
      brief screening instruments. OBJECTIVE: to describe the prevalence and severity
      of dementia, depression, behavioural problems and relevant medication use in a
      representative sample of residential and nursing care home residents.
      DESIGN/SETTING: a survey conducted in 15 randomly selected South East London care
      homes. Consensus clinical dementia diagnoses were made from multi-source
      information, and the Clinical Dementia Rating (CDR) Scale applied. Depression was
      ascertained using the Cornell Depression in Dementia Scale and
      psychological/behavioural problems using the Neuropsychiatric Inventory (NPI).
      PARTICIPANTS: three hundred and one residents with a mean (SD) age of 83.5 (9.8)
      and 65.8% female were included. RESULTS: dementia (CDR 1-3) prevalence was 75.1%
      overall, 55.8% in residential homes, 91.0% in residential elderly mentally infirm
      care and 77.0% in nursing homes. Depression prevalences were 26.5, 22.0 and
      29.6%, respectively, and mean (95% CI) NPI severity scores 3.99 (3.47-4.50), 6.34
      (5.29-7.39) and 6.10 (5.50-6.70) with 87.3% of the sample exhibiting at least one
      NPI symptom. Antidepressants were prescribed in 25.6, 25.0 and 41.3%,
      respectively, and antipsychotics in 7.0, 34.1 and 19.1%. CONCLUSION: dementia is
      substantially more common in care homes than recorded diagnoses would suggest,
      but studies using brief screening instruments may overestimate prevalence. High
      prevalences of depressive and/or behavioural symptoms and psychotropic use
      suggest significant unmet need.

PMID- 24855113
TI  - Effect of cold indoor environment on physical performance of older women living
      in the community.
AB  - BACKGROUND: the effects of cold on older persons' body and mind are not well
      documented, but with an increased number of older people with decreasing physical
      performance, these possible effects need to be understood. OBJECTIVE: to
      investigate the effect of cold indoor environment on physical performance of
      older women. DESIGN: cross-sectional experimental study with two test conditions.
      SETTING: movement laboratory in a climate chamber. SUBJECTS: eighty-eight
      community-dwelling, cognitively unimpaired older women (mean age 78 years).
      METHODS: participants were exposed to moderately cold (15 degrees C) and
      warm/normal (25 degrees C) temperature in a climate chamber in random order with
      an interval of 1 week. The assessment protocol included leg extensor power
      (Nottingham Power Rig), sit-to-stand performance velocity (linear encoder), gait
      speed, walk-ratio (i.e. step length/cadence on an instrumented walk way), maximal
      quadriceps and hand grip strength. RESULTS: physical performance was lower in 15
      degrees C room temperature compared with 25 degrees C room temperature for leg
      extensor power (P < 0.0001), sit-to-stand performance velocity (P < 0.0001), gait
      speed (P < 0.0001), walk-ratio (P = 0.016) and maximal quadriceps strength (P =
      0.015), but not for hand grip strength. CONCLUSION: in healthy older women a
      moderately cold indoor environment decreased important physical performance
      measures necessary for independent living.

PMID- 24855114
TI  - Stimulus Dependence of Gamma Oscillations in Human Visual Cortex.
AB  - A striking feature of some field potential recordings in visual cortex is a
      rhythmic oscillation within the gamma band (30-80 Hz). These oscillations have
      been proposed to underlie computations in perception, attention, and information
      transmission. Recent studies of cortical field potentials, including human
      electrocorticography (ECoG), have emphasized another signal within the gamma
      band, a nonoscillatory, broadband signal, spanning 80-200 Hz. It remains unclear
      under what conditions gamma oscillations are elicited in visual cortex, whether
      they are necessary and ubiquitous in visual encoding, and what relationship they
      have to nonoscillatory, broadband field potentials. We demonstrate that ECoG
      responses in human visual cortex (V1/V2/V3) can include robust narrowband gamma
      oscillations, and that these oscillations are reliably elicited by some spatial
      contrast patterns (luminance gratings) but not by others (noise patterns and many
      natural images). The gamma oscillations can be conspicuous and robust, but
      because they are absent for many stimuli, which observers can see and recognize,
      the oscillations are not necessary for seeing. In contrast, all visual stimuli
      induced broadband spectral changes in ECoG responses. Asynchronous neural signals
      in visual cortex, reflected in the broadband ECoG response, can support
      transmission of information for perception and recognition in the absence of
      pronounced gamma oscillations. 

PMID- 24855116
TI  - Medial lower lid epiblepharon repair solely by skin-redraping medial
      epicanthoplasty.
AB  - BACKGROUND/AIMS: To evaluate clinical efficacy of a procedure using solely skin
      redraping medial epicanthoplasty without traditional epiblepharon correction
      methods in patients with medial lower lid epiblepharon with epicanthal fold.
      METHODS: This clinical practice study included 24 eyes of 12 patients with medial
      lower lid epiblepharon who underwent epiblepharon repairs from January to
      September 2012. The patients included were those whose cilia touch disappeared
      with medial epicanthal fold traction for temporary medial epicanthal fold repair
      during preoperative examination. The patients underwent the sole procedure of
      skin-redraping medial epicanthoplasty. RESULTS: The mean age was 7.50 +/- 3.23
      years and the mean period of follow-up was 12.5 +/- 3.80 months. Complete
      correction of cilia touch was observed in all patients. Surgical complications
      such as canalicular injury, skin fold, severe hypertrophic scar and excessive
      haemorrhage were not observed in any patients. Cosmetic results of surgical
      intervention were considered satisfactory by all patients, including one case of
      mild scar formation. There was no recurrence during the follow-up period.
      CONCLUSIONS: For patients with medial lower lid epiblepharon with epicanthal fold
      without excessive skin and muscle, a simple skin-redraping medial epicanthoplasty
      without traditional epiblepharon correction methods showed good results of
      epiblepharon repair.

PMID- 24855115
TI  - The reliability of parafoveal cone density measurements.
AB  - BACKGROUND: Adaptive optics scanning light ophthalmoscopy (AOSLO) enables direct
      visualisation of the cone mosaic, with metrics such as cone density and cell
      spacing used to assess the integrity or health of the mosaic. Here we examined
      the interobserver and inter-instrument reliability of cone density measurements.
      METHODS: For the interobserver reliability study, 30 subjects with no vision
      limiting pathology were imaged. Three image sequences were acquired at a single
      parafoveal location and aligned to ensure that the three images were from the
      same retinal location. Ten observers used a semiautomated algorithm to identify
      the cones in each image, and this was repeated three times for each image. To
      assess inter-instrument reliability, 20 subjects were imaged at eight parafoveal
      locations on one AOSLO, followed by the same set of locations on the second
      AOSLO. A single observer manually aligned the pairs of images and used the
      semiautomated algorithm to identify the cones in each image. RESULTS: Based on a
      factorial study design model and a variance components model, the interobserver
      study's largest contribution to variability was the subject (95.72%) while the
      observer's contribution was only 1.03%. For the inter-instrument study, an
      average cone density intraclass correlation coefficient (ICC) of between 0.931
      and 0.975 was calculated. CONCLUSIONS: With the AOSLOs used here, reliable cone
      density measurements can be obtained between observers and between instruments.
      Additional work is needed to determine how these results vary with differences in
      image quality.

PMID- 24855118
TI  - Increasing efficiency for estimating treatment-biomarker interactions with
      historical data.
AB  - Detecting a treatment-biomarker interaction, which is a task better suited for
      large sample sizes, in a phase II trial, which has a small sample size, is
      challenging. In this paper, we investigate how two plausibly available sources of
      historical data may contain partial information to help estimate the treatment
      biomarker interaction parameter in a randomized phase II study. The parameter is
      not identified in either historical dataset alone; nonetheless, both can provide
      some information about the parameter and, consequently, increase the precision of
      its estimate. To illustrate the potential for gains in efficiency and
      implications for the design of the study, we consider Gaussian outcomes and
      biomarker data and calculate the asymptotic variance using the expected Fisher
      information matrix. We quantify the gain in efficiency both through a numerical
      study and, in a simplified setting, insights derived from an algebraic
      development of the problem. We find that a non-negligible gain in precision is
      possible, even if the historical and prospective data do not arise from identical
      underlying models.

PMID- 24855117
TI  - Vulnerability of the developing heart to oxygen deprivation as a cause of
      congenital heart defects.
AB  - BACKGROUND: The heart develops under reduced and varying oxygen concentrations,
      yet there is little understanding of oxygen metabolism in the normal and mal
      development of the heart. Here we used a novel reagent, the ODD-Luc hypoxia
      reporter mouse (oxygen degradation domain, ODD) of Hif-1alpha fused to Luciferase
      (Luc), to assay the activity of the oxygen sensor, prolyl hydroxylase, and oxygen
      reserve, in the developing heart. We tested the role of hypoxia-dependent
      responses in heart development by targeted inactivation of Hif-1alpha. METHODS
      AND RESULTS: ODD-Luciferase activity was 14-fold higher in mouse embryonic day
      10.5 (E10.5) versus adult heart and liver tissue lysates. ODD-Luc activity
      decreased in 2 stages, the first corresponding with the formation of a functional
      cardiovascular system for oxygen delivery at E15.5, and the second after birth
      consistent with complete oxygenation of the blood and tissues. Reduction of
      maternal inspired oxygen to 8% for 4 hours caused minimal induction of luciferase
      activity in the maternal tissues but robust induction in the embryonic tissues in
      proportion to the basal activity, indicating a lack of oxygen reserve, and
      corresponding induction of a hypoxia-dependent gene program. Bioluminescent
      imaging of intact embryos demonstrated highest activity in the outflow portion of
      the E13.5 heart. Hif-1alpha inactivation or prolonged hypoxia caused outflow and
      septation defects only when targeted to this specific developmental window.
      CONCLUSIONS: Low oxygen concentrations and lack of oxygen reserve during a
      critical phase of heart organogenesis may provide a basis for vulnerability to
      the development of common septation and conotruncal heart defects.

PMID- 24855119
TI  - Longitudinal data subject to irregular observation: A review of methods with a
      focus on visit processes, assumptions, and study design.
AB  - When data are collected longitudinally, measurement times often vary among
      patients. This is of particular concern in clinic-based studies, for example
      retrospective chart reviews. Here, typically no two patients will share the same
      set of measurement times and moreover, it is likely that the timing of the
      measurements is associated with disease course; for example, patients may visit
      more often when unwell. While there are statistical methods that can help
      overcome the resulting bias, these make assumptions about the nature of the
      dependence between visit times and outcome processes, and the assumptions differ
      across methods. The purpose of this paper is to review the methods available with
      a particular focus on how the assumptions made line up with visit processes
      encountered in practice. Through this we show that no one method can handle all
      plausible visit scenarios and suggest that careful analysis of the visit process
      should inform the choice of analytic method for the outcomes. Moreover, there are
      some commonly encountered visit scenarios that are not handled well by any
      method, and we make recommendations with regard to study design that would
      minimize the chances of these problematic visit scenarios arising.

PMID- 24855120
TI  - High level of HIV-1 resistance in patients failing long-term first-line
      antiretroviral therapy in Mali.
AB  - OBJECTIVES: In resource-limited settings, few data are available on virological
      failure after long-term first-line antiretroviral therapy. This study
      characterized the genotypic resistance patterns at the time of failure after at
      least 36 months of a first-line regimen in Mali, West Africa. METHODS: Plasma
      samples from 84 patients who were receiving first-line antiretroviral treatment
      and with an HIV-1 RNA viral load (VL) >1000 copies/mL were analysed. Genotypic
      resistance testing was performed and HIV-1 drug resistance was interpreted
      according to the latest version of the National Agency for HIV and Hepatitis
      Research algorithm. RESULTS: At the time of resistance testing, patients had been
      treated for a median of 60 months (IQR 36-132 months) and had a median CD4 cell
      count of 292 cells/mm(3) (IQR 6-1319 cells/mm(3)), a median HIV-1 RNA level of
      28266 copies/mL (IQR 1000-2 93 495 copies/mL) and a median genotypic
      susceptibility score of 1 (IQR 1-4). The prevalence of nucleoside reverse
      transcriptase inhibitor (NRTI) and non-nucleoside reverse transcriptase inhibitor
      (NNRTI) resistance mutations was 78% and 82%, respectively. Viruses were
      resistant to at least one drug in 92% of cases. Although etravirine and
      rilpivirine were not used in the first-line regimens, viruses were resistant to
      etravirine in 34% of cases and to rilpivirine in 49% of cases. The treatment
      duration, median number of NRTI and NNRTI mutations and some reverse
      transcriptase mutations (T215Y/F/N, L210W, L74I, M41L and H221Y) were associated
      with the VL at virological failure. CONCLUSIONS: This study demonstrated a high
      level of resistance to NRTIs and NNRTIs, compromising second-generation NNRTIs,
      for patients who stayed on long-term first-line regimens. It is crucial to expand
      the accessibility of virological testing in resource-limited settings to limit
      the expansion of resistance and preserve second-line treatment efficacy.

PMID- 24855122
TI  - Resistance profiles of coagulase-negative staphylococci contaminating blood
      cultures predict pathogen resistance and patient mortality.
AB  - OBJECTIVES: Blood culture isolates are the cornerstone of adequate antibiotic
      treatment. However, many blood cultures are contaminated with bacteria residing
      on the skin, the most common contaminants being coagulase-negative staphylococci
      (CoNS). Such contaminated cultures are mostly disregarded. In this retrospective
      study, we show that contaminated cultures contain diagnostic information. We
      tested the association between resistance profiles of CoNS contaminants and those
      of the actual infecting bacteria isolated subsequently from the same patient, as
      well as their association with short-term mortality. METHODS: We identified all
      patients in Rabin Medical Center, Israel, with positive blood cultures during
      2009-12. Data included patient demographics, hospitalization records,
      comorbidities, blood culture results and date of death. RESULTS: Our cohort
      consists of 2518 patients with 5290 blood cultures, where 1124 patients had 1664
      blood cultures with CoNS contaminants. High overall CoNS resistance predicted
      high overall resistance of the subsequent bacterial isolates (P<0.004 and
      P<0.0006, for Gram-positive and -negative bacteria, respectively). Moreover, the
      resistance of CoNS contaminants to a specific antibiotic predicted the resistance
      of the subsequent bacterial isolates to that antibiotic (OR=5.55, 95% CI=3.54
      8.66, P<10(-15) and OR=2.47, 95% CI=1.61-3.78, P<3 *10(-5), for Gram-positive and
      -negative bacteria, respectively). Finally, highly resistant CoNS isolates were
      associated with higher short-term mortality (hazard ratio=1.71, 95% CI=1.4-2.11,
      P<10(-6)). CONCLUSIONS: Resistance patterns of CoNS contaminants predict specific
      and overall resistance of subsequent blood culture isolates and short-term
      mortality. These results may help predict patient mortality and correct empirical
      antibiotic therapy if blood cultures yield contaminant bacteria and imply that
      skin commensals may serve as an additional, non-invasive, diagnostic tool.

PMID- 24855121
TI  - Simvastatin increases the in vivo activity of the first-line tuberculosis
      regimen.
AB  - BACKGROUND: The need to develop new, improved treatments for tuberculosis (TB)
      remains urgent, and the repurposing of existing drugs represents a possible
      shortcut to market. Recently, there has been significant interest in host
      directed adjuvant therapy to enhance bacillary killing. HMG-CoA reductase
      inhibitors (statins), which are among the most commonly prescribed drugs, have
      immunomodulatory properties and improve the clinical outcomes of bacterial
      infections. METHODS: We studied the tuberculocidal activity of simvastatin alone
      and in combination with first-line anti-TB drugs in J774 macrophages and during
      chronic TB infection. RESULTS: Exposure to 5 MUM simvastatin significantly
      increased the tuberculocidal activity of isoniazid in J774 macrophages at Day 3
      after infection versus isoniazid alone (P=0.02). Similarly, relative to the
      standard oral regimen of rifampicin (10 mg/kg), isoniazid (10 mg/kg) and
      pyrazinamide (150 mg/kg) given five times weekly, the addition of 25 mg/kg
      simvastatin enhanced bacillary killing, reducing the number of lung cfu by an
      additional 1 log10 at Day 28 (P<0.01) and by a further 1.25 log10 at Day 56
      (P<0.01). CONCLUSIONS: The potential additive activity of simvastatin to first
      line TB treatment holds promise. However, further studies to identify the optimal
      statin and dosing are required. In addition the ability of combination treatment
      with statins to accelerate the time required to achieve a stable cure remains to
      be explored.

PMID- 24855123
TI  - Emergence of trimethoprim resistance gene dfrG in Staphylococcus aureus causing
      human infection and colonization in sub-Saharan Africa and its import to Europe.
AB  - OBJECTIVES: Co-trimoxazole (trimethoprim/sulfamethoxazole) is clinically valuable
      in treating skin and soft tissue infections (SSTIs) caused by community
      associated methicillin-resistant Staphylococcus aureus (MRSA). The genetic basis
      of emerging trimethoprim/sulfamethoxazole resistance in S. aureus from Africa is
      unknown. Such knowledge is essential to anticipate its further spread. We
      investigated the molecular epidemiology of trimethoprim resistance in S. aureus
      collected in and imported from Africa. METHODS: Five hundred and ninety-eight
      human S. aureus isolates collected at five locations across sub-Saharan Africa
      [Gabon, Namibia, Nigeria (two) and Tanzania] and 47 isolates from travellers
      treated at six clinics in Europe because of SSTIs on return from Africa were
      tested for susceptibility to trimethoprim, sulfamethoxazole and
      trimethoprim/sulfamethoxazole, screened for genes mediating trimethoprim
      resistance in staphylococci [dfrA (dfrS1), dfrB, dfrG and dfrK] and assigned to
      spa genotypes and clonal complexes. RESULTS: In 313 clinical and 285 colonizing
      S. aureus from Africa, 54% of isolates were resistant to trimethoprim, 21% to
      sulfamethoxazole and 19% to trimethoprim/sulfamethoxazole. We found that 94% of
      trimethoprim resistance was mediated by the dfrG gene. Of the 47 S. aureus
      isolates from travellers with SSTIs, 27 (57%) were trimethoprim resistant and
      carried dfrG. Markers of trimethoprim resistance other than dfrG were rare. The
      presence of dfrG genes in S. aureus was neither geographically nor clonally
      restricted. CONCLUSIONS: dfrG, previously perceived to be an uncommon cause of
      trimethoprim resistance in human S. aureus, is widespread in Africa and abundant
      in imported S. aureus from ill returning travellers. These findings may
      foreshadow the loss of trimethoprim/sulfamethoxazole for the empirical treatment
      of SSTIs caused by community-associated MRSA.

PMID- 24855124
TI  - Plasmodium falciparum multidrug resistance protein 1 (pfmrp1) gene and its
      association with in vitro drug susceptibility of parasite isolates from north
      east Myanmar.
AB  - OBJECTIVES: Plasmodium falciparum multidrug resistance protein 1 (pfmrp1) has
      recently emerged as an important determinant of drug resistance and mutations in
      the gene have been associated with several drugs. The aim of this study was to
      understand the level of genetic diversity in pfmrp1 and to determine the
      association of different mutations with altered drug susceptibilities of P.
      falciparum. METHODS: We analysed 193 sequences of pfmrp1 from South-East Asia,
      west Asia, Africa, Oceania and South America. We measured the level of genetic
      diversity and determined signatures of selection on the gene. In vitro
      susceptibilities of 28 P. falciparum isolates from north-east Myanmar to a panel
      of seven commonly used antimalarials were determined. Statistical analysis was
      performed to determine the association of different mutations with in vitro drug
      susceptibilities. RESULTS: A total of 28 single nucleotide polymorphisms were
      identified in 193 sequences, of which 22 were non-synonymous. Whereas mutations
      in the pfmrp1 gene were conserved among different countries within a continent,
      they were different between continents. Seven non-synonymous mutations were
      identified in the north-east Myanmar isolates; all were relatively frequent in
      this region as well as in other neighbouring countries. Molecular evolutionary
      analysis detected signatures of positive selection on the gene. Moreover, some
      mutations in this gene were found to be associated with reduced susceptibilities
      to chloroquine, mefloquine, pyronaridine and lumefantrine. CONCLUSIONS: Evidence
      of the positive selection of pmfrp1 and its association with the susceptibilities
      of parasites to multiple drugs signifies its potential as an important candidate
      for monitoring drug resistance.

PMID- 24855125
TI  - Effect of meropenem administration in extended infusion on the clinical outcome
      of febrile neutropenia: a retrospective observational study.
AB  - OBJECTIVES: Information on the efficacy of extended meropenem administration in
      neutropenic patients is scarce. Our objective was to determine whether the
      administration of meropenem in a 4 h extended infusion (EI) leads to a better
      clinical outcome in patients with febrile neutropenia than the conventional short
      infusion (SI). METHODS: This was a retrospective observational study. The
      subjects were neutropenic patients who presented with fever after receiving
      haematopoietic stem-cell transplantation or induction chemotherapy for acute
      myeloid leukaemia. The primary endpoint was the success of treatment after 5 days
      of meropenem therapy, defined as follows: the disappearance of fever leading to a
      maintained (>= 24 h) feverless state; the resolution or improvement of the
      clinical signs and symptoms of infection; the absence of persistent or
      breakthrough bacteraemia; and no additional antibiotics prescribed because of an
      unsatisfactory clinical evolution. RESULTS: Eighty-eight patients received
      meropenem (1 g/8 h) in SI and 76 received the same dose in EI. Treatment success
      on day 5 was superior in the EI group [52/76 (68.4%) versus 36/88 (40.9%);
      P<0.001]. Meropenem administered in EI was independently associated with success
      (OR 3.13, 95% CI 1.61-6.10). Fewer additional antibiotics were prescribed in the
      EI group during the first 5 days of treatment [20/76 (26.3%) versus 44/88
      (50.0%); P=0.002]. Using Kaplan-Meier survival analysis a more prompt
      defervescence and a faster decrease in C-reactive protein concentration were
      observed in the EI group (P=0.021 and P=0.037, respectively). There were no
      significant differences in the length of hospital stay and in the mortality rate.
      CONCLUSIONS: Meropenem administration in EI results in a better clinical outcome
      for febrile neutropenia episodes, with fewer additional antibiotics needed.

PMID- 24855126
TI  - Detection of mutations associated with isoniazid resistance in multidrug
      resistant Mycobacterium tuberculosis clinical isolates.
AB  - OBJECTIVES: To determine the prevalence of isoniazid resistance-conferring
      mutations among multidrug-resistant (MDR) isolates of Mycobacterium tuberculosis
      from Poland. METHODS: Nine genetic loci, including structural genes (katG, inhA,
      ahpC, kasA, ndh, nat and mshA) and regulatory regions (i.e. the mabA-inhA
      promoter and oxyR-ahpC intergenic region) of 50 MDR M. tuberculosis isolates
      collected throughout Poland were PCR-amplified in their entirety and screened for
      mutations by direct sequencing methodology. RESULTS: Forty-six (92%) MDR M.
      tuberculosis isolates had mutations in the katG gene, and the katG Ser315Thr
      substitution predominated (72%). Eight (16%) isolates (six with a mutated katG
      allele) had mutations in the inhA promoter region and two such isolates also had
      single inhA structural gene mutations. Mutations in the oxyR-ahpC locus were
      found in five (10%) isolates, of which all but one had at least one additional
      mutation in katG. Mutations in the remaining genetic loci (kasA, ndh, nat and
      mshA) were detected in 12 (24%), 4 (8%), 5 (10%) and 17 (34%) MDR isolates,
      respectively. All non-synonymous mutants for these genes harboured mutations in
      katG. One isolate had no mutations in any of the analysed loci. CONCLUSIONS: This
      study accentuates the usefulness of katG and inhA promoter mutations as
      predictive markers of isoniazid resistance. Testing only for katG 315 and inhA 
      15 mutations would detect isoniazid resistance in 84% of the MDR M. tuberculosis
      sample. This percentage would increase to 96% if the sequence analysis was
      extended to the entire katG gene. Analysis of the remaining genetic loci did not
      contribute greatly to the identification of isoniazid resistance.

PMID- 24855127
TI  - Using generic preference-based measures in mental health: psychometric validity
      of the EQ-5D and SF-6D.
AB  - BACKGROUND: Generic preference-based measures (EuroQoL-5D (EQ-5D) and SF-6D) are
      used in the economic evaluation of mental health interventions. However, there
      are inconsistent findings regarding their psychometric properties. AIMS: To
      investigate the psychometric properties of the EQ-5D and SF-6D in different
      mental health conditions, using seven existing data-sets. METHOD: The construct
      validity and responsiveness of the measures were assessed in comparison with
      condition-specific indicators. RESULTS: Evidence for construct validity and
      responsiveness in common mental health and personality disorders was found
      (correlations 0.22-0.64; effect sizes 0.37-1.24; standardised response means 0.45
      1.31). There was some evidence for validity in schizophrenia (correlations 0.05
      0.43), but responsiveness was unclear. CONCLUSIONS: EQ-5D and SF-6D can be used
      in the economic evaluation of interventions for common mental health problems
      with some confidence. In schizophrenia, a preference-based measure focused on the
      impact of mental health should be considered.

PMID- 24855128
TI  - Parent-child interaction and oxytocin production in pre-schoolers with autism
      spectrum disorder.
AB  - BACKGROUND: Autism spectrum disorder (ASD) is associated with genetic risk on the
      oxytocin system, suggesting oxytocin involvement in ASD; yet oxytocin functioning
      in young children with ASD is unknown. AIMS: To assess baseline oxytocin in pre
      schoolers with ASD and test whether oxytocin production may be enhanced by parent
      child contact. METHOD: Forty pre-schoolers with high-functioning ASD were matched
      with 40 typically developing controls. Two home visits included an identical 45
      minute social battery once with the mother and once with the father. Four saliva
      oxytocin samples were collected from each parent and the child during each visit.
      RESULTS: Children with ASD had lower baseline oxytocin. Following 20 min of
      parent-child interactions, oxytocin normalised and remained high during social
      contact. Fifteen minutes after contact, oxytocin fell to baseline. Oxytocin
      correlated with parent-child social synchrony in both groups. CONCLUSIONS:
      Oxytocin dysfunction in ASD is observed in early childhood. The quick improvement
      in oxytocin production following parent-child contact underscores the
      malleability of the system and charts future directions for attachment-based
      behavioural and pharmacological interventions.

PMID- 24855129
TI  - Vocational rehabilitation in early psychosis: cluster randomised trial.
AB  - BACKGROUND: Individual placement and support (IPS) is effective in helping
      patients return to work but is poorly implemented because of clinical ambivalence
      and fears of relapse. AIMS: To assess whether a motivational intervention
      (motivational interviewing) directed at clinical staff to address ambivalence
      about employment improved patients' occupational outcomes. METHOD: Two of four
      early intervention teams that already provided IPS were randomised to receive
      motivational interviewing training for clinicians, focused on attitudinal
      barriers to employment. The trial was registered with the International Standard
      Randomised Controlled Trial Register (ISRCTN71943786). RESULTS: Of 300 eligible
      participants, 159 consented to the research. Occupational outcomes were obtained
      for 134 patients (85%) at 12-month follow-up. More patients in the intervention
      teams than in the IPS-only teams achieved employment by 12 months (29/68 v.
      12/66). A random effects logistic regression accounting for clustering by care
      coordinator, and adjusted for participants' gender, ethnicity, educational and
      employment history and clinical status scores, confirmed superiority of the
      intervention (odds ratio = 4.3, 95% CI 1.5-16.6). CONCLUSIONS: Employment
      outcomes were enhanced by addressing clinicians' ambivalence about their patients
      returning to work.

PMID- 24855130
TI  - Soft tissue augmentation with PMMA-microspheres for the treatment of HIV
      associated buttock lipodystrophy.
AB  - Progression of lipodystrophy syndrome is a big challenge in HIV treatment.
      Nowadays, fat loss at the lower part of buttocks has become another problem as
      patients have started to complain that it is painful to be seated for a long time
      and/or on hard surfaces. We developed a method for buttock lipoatrophy treatment
      with PMMA-microspheres, as silicone prostheses and autologous fat transplant were
      not completely efficient. The treatment consisted of net-crossed injections, in
      the subcutaneous layer, of a 30% PMMA-microspheres solution on the atrophic areas
      of the buttock. One hundred and fifty-four patients were included. The amount of
      PMMA-microspheres used to treat buttock lipoatrophy depended on the degree of
      atrophy and size of the area to be treated. Patients were satisfied with this
      treatment and reported to be more comfortable to be seated for longer period of
      time. We demonstrated that soft tissue augmentation with PMMA-microspheres is
      safe and efficient for the treatment of buttock lipoatrophy associated with HIV
      lipodystrophy.

PMID- 24855131
TI  - Microscopy outperformed in a comparison of five methods for detecting Trichomonas
      vaginalis in symptomatic women.
AB  - In the UK, despite its low sensitivity, wet mount microscopy is often the only
      method of detecting Trichomonas vaginalis infection. A study was conducted in
      symptomatic women to compare the performance of five methods for detecting T.
      vaginalis: an in-house polymerase chain reaction (PCR); Aptima T. vaginalis kit;
      OSOM (r)Trichomonas Rapid Test; culture and microscopy. Symptomatic women
      underwent routine testing; microscopy and further swabs were taken for molecular
      testing, OSOM and culture. A true positive was defined as a sample that was
      positive for T. vaginalis by two or more different methods. Two hundred and forty
      six women were recruited: 24 patients were positive for T. vaginalis by two or
      more different methods. Of these 24 patients, 21 patients were detected by real
      time PCR (sensitivity 88%); 22 patients were detected by the Aptima T. vaginalis
      kit (sensitivity 92%); 22 patients were detected by OSOM (sensitivity 92%); nine
      were detected by wet mount microscopy (sensitivity 38%); and 21 were detected by
      culture (sensitivity 88%). Two patients were positive by just one method and were
      not considered true positives. All the other detection methods had a sensitivity
      to detect T. vaginalis that was significantly greater than wet mount microscopy,
      highlighting the number of cases that are routinely missed even in symptomatic
      women if microscopy is the only diagnostic method available.

PMID- 24855132
TI  - Cervicovestibular rehabilitation in sport-related concussion: a randomised
      controlled trial.
AB  - BACKGROUND/AIM: Concussion is a common injury in sport. Most individuals recover
      in 7-10 days but some have persistent symptoms. The objective of this study was
      to determine if a combination of vestibular rehabilitation and cervical spine
      physiotherapy decreased the time until medical clearance in individuals with
      prolonged postconcussion symptoms. METHODS: This study was a randomised
      controlled trial. Consecutive patients with persistent symptoms of dizziness,
      neck pain and/or headaches following a sport-related concussion (12-30 years, 18
      male and 13 female) were randomised to the control or intervention group. Both
      groups received weekly sessions with a physiotherapist for 8 weeks or until the
      time of medical clearance. Both groups received postural education, range of
      motion exercises and cognitive and physical rest until asymptomatic followed by a
      protocol of graded exertion. The intervention group also received cervical spine
      and vestibular rehabilitation. The primary outcome of interest was medical
      clearance to return to sport, which was evaluated by a study sport medicine
      physician who was blinded to the treatment group. RESULTS: In the treatment
      group, 73% (11/15) of the participants were medically cleared within 8 weeks of
      initiation of treatment, compared with 7% (1/14) in the control group. Using an
      intention to treat analysis, individuals in the treatment group were 3.91 (95% CI
      1.34 to 11.34) times more likely to be medically cleared by 8 weeks. CONCLUSIONS:
      A combination of cervical and vestibular physiotherapy decreased time to medical
      clearance to return to sport in youth and young adults with persistent symptoms
      of dizziness, neck pain and/or headaches following a sport-related concussion.
      TRIAL REGISTRATION NUMBER: NCT01860755.

PMID- 24855133
TI  - The Impact of Cultural Competence Education on Short-Term Medical Mission Groups:
      A Pilot Study.
AB  - BACKGROUND: There are large numbers of short-term medical mission (STMM) groups
      traveling yearly from the United States to underdeveloped countries. Medical
      professionals educated in the Western biomedical model of treatment have an
      ethnocentric view of how to treat illness. PURPOSE: The purpose of this pilot
      study was to demonstrate that a 2-hour culturally sensitive educational program
      administered to medical professionals travelling to Haiti on a STMM could raise
      their cultural competency as measured by a specific tool. METHOD: The
      participants were invited to a short educational program designed to help them
      understand their own biases and make better treatment decisions for their
      patients based on the five constructs of Dr. Campinha-Bacote's cultural
      competence model. FINDINGS: Following an evidence-based educational program, the
      members of the STMM groups demonstrated improved levels of cultural competency.
      IMPLICATIONS: This program could provide an appropriate way to raise the cultural
      competency of medical mission health care providers.

PMID- 24855134
TI  - Social Ecology of Adherence to Hypertension Treatment in Latino Migrant and
      Seasonal Farmworkers.
AB  - PURPOSE: This study explored Latino migrant/seasonal farmworkers' (MSFWs')
      adherence to hypertension treatment. DESIGN: A cross-sectional correlational
      study was conducted. METHOD: Forty-five Latino MSFWs from two farmworker health
      clinics completed Spanish versions of the Morisky Medication Adherence Scale, the
      Blood Pressure Knowledge Scale and Blood Pressure Self-Care Scale, the Perceived
      Stress Scale, the Acculturation Rating Scale for Mexican Americans-II, the Short
      Assessment of Health Literacy for Spanish-Speaking Adults, health care access
      questions, and blood pressure measurements. RESULTS: MSFWs had poor medication
      adherence (51%). Blood pressure knowledge, perceived stress, acculturation,
      health literacy, and health care access accounted for 49% of the variance in
      blood pressure self-care. Higher acculturation level and health literacy were
      associated with better blood pressure control (p = .01). DISCUSSION: MSFWs had
      poor medication adherence and blood pressure control. Blood pressure knowledge
      and acculturation played a role in blood pressure self-care. IMPLICATIONS:
      Culturally appropriate educational programs are needed to help MSFWs' adherence
      to hypertension treatment.

PMID- 24855135
TI  - Reduced skeletal muscle AMPK and mitochondrial markers do not promote age-induced
      insulin resistance.
AB  - In both rodents and humans, aging-associated reductions in skeletal muscle AMP
      activated protein kinase (AMPK) activity and mitochondrial function have been
      linked to the development of skeletal muscle insulin resistance. However, whether
      reductions in skeletal muscle AMPK and mitochondrial capacity actually
      precipitate the development of aging-induced insulin resistance is not known.
      Mice lacking both isoforms of the AMPK beta-subunit in skeletal muscle (AMPK-MKO)
      have no detectable AMPK activity and are characterized by large reductions in
      exercise capacity, mitochondrial content, and contraction-stimulated glucose
      uptake making them an ideal model to determine whether reductions in AMPK and
      mitochondrial content promote the development of aging-induced insulin
      resistance. In the current study we find that a lack of skeletal muscle AMPK
      results in a life-long reduction in mitochondrial activity but does not affect
      body mass, body composition, glucose tolerance, or insulin sensitivity as
      measured by hyperinsulinemic-euglycemic clamp in mice of old age (18 mo). These
      data demonstrate that reductions in skeletal muscle AMPK and mitochondrial
      activity do not cause the development of age-induced insulin resistance. 

PMID- 24855136
TI  - Effect of abdominal binding on respiratory mechanics during exercise in athletes
      with cervical spinal cord injury.
AB  - We asked whether elastic binding of the abdomen influences respiratory mechanics
      during wheelchair propulsion in athletes with cervical spinal cord injury (SCI).
      Eight Paralympic wheelchair rugby players with motor-complete SCI (C5-C7)
      performed submaximal and maximal incremental exercise tests on a treadmill, both
      with and without abdominal binding. Measurements included pulmonary function,
      pressure-derived indices of respiratory mechanics, operating lung volumes, tidal
      flow-volume data, gas exchange, blood lactate, and symptoms. Residual volume and
      functional residual capacity were reduced with binding (77 +/- 18 and 81 +/- 11%
      of unbound, P < 0.05), vital capacity was increased (114 +/- 9%, P < 0.05),
      whereas total lung capacity was relatively well preserved (99 +/- 5%). During
      exercise, binding introduced a passive increase in transdiaphragmatic pressure,
      due primarily to an increase in gastric pressure. Active pressures during
      inspiration were similar across conditions. A sudden, sustained rise in operating
      lung volumes was evident in the unbound condition, and these volumes were shifted
      downward with binding. Expiratory flow limitation did not occur in any subject
      and there was substantial reserve to increase flow and volume in both conditions.
      Vo2 was elevated with binding during the final stages of exercise (8-12%, P <
      0.05), whereas blood lactate concentration was reduced (16-19%, P < 0.05).
      Vo2/heart rate slopes were less steep with binding (62 +/- 35 vs. 47 +/- 24
      ml/beat, P < 0.05). Ventilation, symptoms, and work rates were similar across
      conditions. The results suggest that abdominal binding shifts tidal breathing to
      lower lung volumes without influencing flow limitation, symptoms, or exercise
      tolerance. Changes in respiratory mechanics with binding may benefit O2 transport
      capacity by an improvement in central circulatory function. 

PMID- 24855138
TI  - Effects of 12-wk eccentric calf muscle training on muscle-tendon glucose uptake
      and SEMG in patients with chronic Achilles tendon pain.
AB  - High-load eccentric exercises have been a key component in the conservative
      management of chronic Achilles tendinopathy. This study investigated the effects
      of a 12-wk progressive, home-based eccentric rehabilitation program on ankle
      plantar flexors' glucose uptake (GU) and myoelectric activity and Achilles tendon
      GU. A longitudinal study design with control (n = 10) and patient (n = 10) groups
      was used. Surface electromyography (SEMG) from four ankle plantar flexors and GU
      from the same muscles and the Achilles tendon were measured during submaximal
      intermittent isometric plantar flexion task. The results indicated that the
      symptomatic leg was weaker (P < 0.05) than the asymptomatic leg at baseline, but
      improved (P < 0.001) with eccentric rehabilitation. Additionally, the
      rehabilitation resulted in greater GU in both soleus (P < 0.01) and lateral
      gastrocnemius (P < 0.001) in the symptomatic leg, while the asymptomatic leg
      displayed higher uptake for medial gastrocnemius and flexor hallucis longus (P <
      0.05). While both patient legs had higher tendon GU than the controls (P < 0.05),
      there was no rehabilitation effect on the tendon GU. Concerning SEMG, at
      baseline, soleus showed more relative activity in the symptomatic leg compared
      with both the asymptomatic and control legs (P < 0.05), probably reflecting an
      effort to compensate for the decreased force potential. The rehabilitation
      resulted in greater SEMG activity in the lateral gastrocnemius (P < 0.01) of the
      symptomatic leg with no other within- or between-group differences. Eccentric
      rehabilitation was effective in decreasing subjective severity of Achilles
      tendinopathy. It also resulted in redistribution of relative electrical activity,
      but not metabolic activity, within the triceps surae muscle. 

PMID- 24855137
TI  - Edward F. Adolph Distinguished Lecture: The remarkable anti-aging effects of
      aerobic exercise on systemic arteries.
AB  - Cardiovascular diseases (CVD) remain the leading cause of morbidity and mortality
      in modern societies, and advancing age is the major risk factor for CVD. Arterial
      dysfunction, characterized by large elastic artery stiffening and endothelial
      dysfunction, is the key event leading to age-associated CVD. Our work shows that
      regular aerobic exercise inhibits large elastic artery stiffening with aging
      (optimizes arterial compliance) and preserves endothelial function. Importantly,
      among previously sedentary late middle-aged and older adults, aerobic exercise
      improves arterial stiffness and enhances endothelial function in most groups and,
      therefore, also can be considered a treatment for age-associated arterial
      dysfunction. The mechanisms by which regular aerobic exercise destiffens large
      elastic arteries are incompletely understood, but existing evidence suggests that
      reductions in oxidative stress associated with decreases in both adventitial
      collagen (fibrosis) and advanced glycation end-products (structural protein cross
      linking molecules), play a key role. Aerobic exercise preserves endothelial
      function with aging by maintaining nitric oxide bioavailability via suppression
      of excessive superoxide-associated oxidative stress, and by inhibiting the
      development of chronic low-grade vascular inflammation. Recent work from our
      laboratory supports the novel hypothesis that aerobic exercise may exert these
      beneficial effects by directly inducing protection to aging arteries against
      multiple adverse factors to which they are chronically exposed. Regular aerobic
      exercise should be viewed as a "first line" strategy for prevention and treatment
      of arterial aging and a vital component of a contemporary public health approach
      for reducing the projected increase in population CVD burden. 

PMID- 24855139
TI  - Age-related changes in inter-joint coordination during walking.
AB  - Existing methods to assess inter-joint coordination in human walking have several
      important weaknesses. These methods are unable to define 1) the instantaneous
      changes in coordination within the stride cycle, 2) coordination between multiple
      joints, or 3) the coupling strength of joint rotations rather than their phase
      relationships. The present paper introduces a new method called generalized
      wavelet coherence analysis (GWCA) that solves these three fundamental limitations
      of previous methods. GWCA combines wavelet coherence analysis with a matrix
      correlation method to define instantaneous correlation coefficients as the
      coupling strength for an arbitrary number of joint rotations. The main purpose of
      the present study is to develop GWCA to quantify inter-joint coordination and
      thereby assess age-related differences in the coordination of human gaits. Nine
      young and 19 healthy older persons walked 5 min on a treadmill at three different
      gait speeds. Joint rotations of the lower extremities were assessed by a Vicon
      three-dimensional motion capture system. The main results indicated that the
      older group had significant weaker correlations (t-tests: P < 0.0001) in the
      preswing phase compared with the younger group for all gait speeds. The age
      related differences in inter-joint coordination were more pronounced than the age
      related differences in rotations of the individual joints. The intra-stride
      changes in inter-joint coordination were in agreement with recent findings of
      intra-stride modulations in neural activity in the sensorimotor cortex. Thus
      change in the inter-joint coordination assessed by GWCA might be an early
      indicator of functional decline.

PMID- 24855140
TI  - Genetic characterization of mycobacterial L,D-transpeptidases.
AB  - l,d-Transpeptidases (Ldts) catalyse the formation of 3-3 cross-links in
      peptidoglycans (PGs); however, the role of these enzymes in cell envelope
      physiology is not well understood. Mycobacterial PG contains a higher percentage
      of 3-3 cross-links (~30-80 %) than the PG in most other bacteria, suggesting that
      they are particularly important to mycobacterial cell wall biology. The genomes
      of Mycobacterium tuberculosis and Mycobacterium smegmatis encode multiple Ldt
      genes, but it is not clear if they are redundant. We compared the sequences of
      the Ldt proteins from 18 mycobacterial genomes and found that they can be grouped
      into six classes. We then constructed M. smegmatis strains lacking single or
      multiple Ldt genes to determine the physiological consequence of the loss of
      these enzymes. We report that of the single mutants, only one, DeltaldtC
      (MSMEG_0929, class 5), displayed an increased susceptibility to imipenem - a
      carbapenem antibiotic that inhibits the Ldt enzymes. The invariant cysteine in
      the active site of LdtC was required for function, consistent with its role as an
      Ldt. A triple mutant missing ldtC and both of the class 2 genes displayed
      hypersusceptibility to antibiotics, lysozyme and d-methionine, and had an altered
      cellular morphology. These data demonstrated that the distinct classes of
      mycobacterial Ldts may reflect different, non-redundant functions and that the
      class 5 Ldt was peculiar in that its loss, alone and with the class 2 proteins,
      had the most profound effect on phenotype. 

PMID- 24855142
TI  - Rethinking historical trauma.
AB  - Recent years have seen the rise of historical trauma as a construct to describe
      the impact of colonization, cultural suppression, and historical oppression of
      Indigenous peoples in North America (e.g., Native Americans in the United States,
      Aboriginal peoples in Canada). The discourses of psychiatry and psychology
      contribute to the conflation of disparate forms of violence by emphasizing
      presumptively universal aspects of trauma response. Many proponents of this
      construct have made explicit analogies to the Holocaust as a way to understand
      the transgenerational effects of genocide. However, the social, cultural, and
      psychological contexts of the Holocaust and of post-colonial Indigenous
      "survivance" differ in many striking ways. Indeed, the comparison suggests that
      the persistent suffering of Indigenous peoples in the Americas reflects not so
      much past trauma as ongoing structural violence. The comparative study of
      genocide and other forms of massive, organized violence can do much to illuminate
      both common mechanisms and distinctive features, and trace the looping effects
      from political processes to individual experience and back again. The ethics and
      pragmatics of individual and collective healing, restitution, resilience, and
      recovery can be understood in terms of the self-vindicating loops between
      politics, structural violence, public discourse, and embodied experience. 

PMID- 24855143
TI  - Historicizing historical trauma theory: troubling the trans-generational
      transmission paradigm.
AB  - The premise that "trauma" is transmitted across generations is central to the
      historical trauma discourse currently circulating in indigenous communities and
      professional networks in Canada. Historical trauma may be understood as the
      offspring of two older and apparently antithetical discourses: Native healing,
      and colonial professional critiques of indigenous family life. While the former
      has maintained a therapeutic focus on restoring intergenerational social
      relations, the latter has pathologized indigenous parenting and child-rearing
      practices. The emergence of historical trauma marks a global shift in the moral
      economy by which victimhood status, acquired through individual experiences of
      physical and especially sexual abuse, has come to wield greater currency than
      collective struggles against colonialism. Providers of contemporary indigenous
      healing programmes are drawing simultaneously on trauma discourse, which is seen
      to legitimate individual social suffering, and older therapeutic forms centred on
      sharing local social histories to restore intergenerational continuities and
      collective identity. But these invocations of historical trauma may continue the
      colonial discourse of mental health and social welfare professionals, who blamed
      indigenous parenting practices for children's social problems and failure to
      assimilate. Some contemporary mental health and child development professionals
      have invoked parents' and grandparents' transmission of historical trauma in ways
      which construct indigenous families as pathological, promote an oversimplified,
      universalizing understanding of Canadian colonialism, and divert attention from
      the contemporary continuation of colonial structures and relations. 

PMID- 24855141
TI  - Relocation facilitates the acquisition of short cis-regulatory regions that drive
      the expression of retrogenes during spermatogenesis in Drosophila.
AB  - Retrogenes are functional processed copies of genes that originate via the
      retrotranscription of an mRNA intermediate and often exhibit testis-specific
      expression. Although this expression pattern appears to be favored by selection,
      the origin of such expression bias remains unexplained. Here, we study the
      regulation of two young testis-specific Drosophila retrogenes, Dntf-2r and
      Pros28.1A, using genetic transformation and the enhanced green fluorescent
      protein reporter gene in Drosophila melanogaster. We show that two different
      short (<24 bp) regions upstream of the transcription start sites (TSSs) act as
      testis-specific regulatory motifs in these genes. The Dntf-2r regulatory region
      is similar to the known beta2 tubulin 14-bp testis motif (beta2-tubulin gene
      upstream element 1 [beta2-UE1]). Comparative sequence analyses reveal that this
      motif was already present before the Dntf-2r insertion and was likely driving the
      transcription of a noncoding RNA. We also show that the beta2-UE1 occurs in the
      regulatory regions of other testis-specific retrogenes, and is functional in
      either orientation. In contrast, the Pros28.1A testes regulatory region in D.
      melanogaster appears to be novel. Only Pros28.1B, an older paralog of the
      Pros28.1 gene family, seems to carry a similar regulatory sequence. It is unclear
      how the Pros28.1A regulatory region was acquired in D. melanogaster, but it might
      have evolved de novo from within a region that may have been preprimed for testes
      expression. We conclude that relocation is critical for the evolutionary origin
      of male germline-specific cis-regulatory regions of retrogenes because expression
      depends on either the site of the retrogene insertion or the sequence changes
      close to the TSS thereafter. As a consequence we infer that positive selection
      will play a role in the evolution of these regulatory regions and can often act
      from the moment of the retrocopy insertion. 

PMID- 24855144
TI  - FutureTox II: Contemporary Concepts in Toxicology: "Pathways to prediction: in
      vitro and in silico models for predictive toxicology".

PMID- 24855147
TI  - Performance of Xpert MTB/RIF in induced sputum samples at detecting Mycobacterium
      tuberculosis.

PMID- 24855146
TI  - Outbreak of hepatitis E in urban Bangladesh resulting in maternal and perinatal
      mortality.
AB  - BACKGROUND: Hepatitis E virus (HEV) causes outbreaks of jaundice associated with
      maternal mortality. Four deaths among pregnant women with jaundice occurred in an
      urban community near Dhaka, Bangladesh, in late 2008 and were reported to
      authorities in January 2009. We investigated the etiology and risk factors for
      jaundice and death. METHODS: Field workers identified suspected cases, defined as
      acute onset of yellow eyes or skin, through house-to-house visits. A subset of
      persons with suspected HEV was tested for immunoglobulin M (IgM) antibodies to
      HEV to confirm infection. We used logistic regression analysis to identify risk
      factors for HEV disease and for death. We estimated the increased risk of
      perinatal mortality associated with jaundice during pregnancy. RESULTS: We
      identified 4751 suspected HEV cases during August 2008-January 2009, including 17
      deaths. IgM antibodies to HEV were identified in 56 of 73 (77%) case-patients
      tested who were neighbors of the case-patients who died. HEV disease was
      significantly associated with drinking municipally supplied water. Death among
      persons with HEV disease was significantly associated with being female and
      taking paracetamol (acetaminophen). Among women who were pregnant, miscarriage
      and perinatal mortality was 2.7 times higher (95% confidence interval, 1.2-6.1)
      in pregnancies complicated by jaundice. CONCLUSIONS: This outbreak of HEV was
      likely caused by sewage contamination of the municipal water system. Longer-term
      efforts to improve access to safe water and license HEV vaccines are needed.
      However, securing resources and support for intervention will rely on convincing
      data about the endemic burden of HEV disease, particularly its role in maternal
      and perinatal mortality.

PMID- 24855148
TI  - Reply to El Sahly.

PMID- 24855150
TI  - Alopecia and nail changes associated with voriconazole therapy.
AB  - BACKGROUND: Voriconazole was 1 of 2 antifungal agents recommended for treatment
      of fungal infections associated with injection of contaminated
      methylprednisolone. Alopecia and nail changes are not commonly reported side
      effects of voriconazole. Having noted increasing hair loss among our patients
      treated with voriconazole, we sought to determine the prevalence and
      characteristics of alopecia associated with this agent. METHODS: Patients who
      received voriconazole for at least 1 month for probable or confirmed fungal
      infection were eligible to complete a survey regarding alopecia and nail changes.
      For those patients who reported alopecia, additional questions about reversal of
      hair loss were asked after voriconazole had been stopped for at least 3 months.
      RESULTS: A total of 152 of 175 eligible patients (87%) completed the survey. One
      hundred twenty-five (82%) reported alopecia. Hair loss on the scalp was noted in
      120 (96%), arms and legs in 52 (42%), and eyebrows and eyelashes in 47 each
      (38%). Nineteen patients (15%) reported wearing a wig or hat because of extensive
      hair loss. Alopecia developed a mean (standard deviation) of 75 (54) days after
      initiation of voriconazole. Of 114 patients who were off voriconazole for at
      least 3 months, hair loss had stopped in 94 (82%) and regrowth had begun in 79
      (69%), including those who were changed to either itraconazole or posaconazole.
      Nail changes or loss occurred in 106 (70%) patients. CONCLUSIONS: Alopecia and
      nail changes were common adverse effects associated with voriconazole therapy
      during the multistate fungal outbreak.

PMID- 24855151
TI  - Editorial commentary: successful methadone delivery in East Africa and its global
      implications.

PMID- 24855149
TI  - Methadone treatment for HIV prevention-feasibility, retention, and predictors of
      attrition in Dar es Salaam, Tanzania: a retrospective cohort study.
AB  - BACKGROUND: People who inject drugs (PWID) in Dar es Salaam, Tanzania, have an
      estimated human immunodeficiency virus (HIV) prevalence of 42%-50% compared with
      6.9% among the general population. Extensive evidence supports methadone
      maintenance to lower morbidity, mortality, and transmission of HIV and other
      infectious diseases among PWID. In 2011, the Tanzanian government launched the
      first publicly funded methadone clinic on the mainland of sub-Saharan Africa at
      Muhimbili National Hospital. METHODS: We conducted a retrospective cohort study
      of methadone-naive patients enrolling into methadone maintenance treatment.
      Kaplan-Meier survival curves were constructed to assess retention probability.
      Proportional hazards regression models were used to evaluate the association of
      characteristics with attrition from the methadone program. RESULTS: Overall, 629
      PWID enrolled into methadone treatment during the study. At 12 months, the
      proportion of clients retained in care was 57% (95% confidence interval [CI], 53%
      62%). Compared with those receiving a low dose (<40 mg), clients receiving a
      medium (40-85 mg) (adjusted hazard ratio [aHR], 0.50 [95% CI, .37-.68]) and high
      (>85 mg) (aHR, 0.41 [95% CI, .29-.59]) dose of methadone had a lower likelihood
      of attrition, adjusting for other characteristics. Older clients (aHR, 0.53 per
      10 years [95% CI, .42-.69]) and female clients (aHR, 0.50 [95% CI, .28-.90]) had
      a significantly lower likelihood of attrition, whereas clients who reported a
      history of sexual abuse (aHR, 2.84 [95% CI, 1.24-6.51]) had a significantly
      higher likelihood of attrition. CONCLUSIONS: Patient retention in methadone
      maintenance is comparable to estimates from programs in North America, Europe,
      and Asia. Future implementation strategies should focus on higher doses and
      flexible dosing strategies to optimize program retention and strengthened efforts
      for clients at higher risk of attrition.

PMID- 24855152
TI  - The gut hormone ghrelin partially reverses energy substrate metabolic alterations
      in the failing heart.
AB  - BACKGROUND: The gut-derived hormone ghrelin, especially its acylated form, plays
      a major role in the regulation of systemic metabolism and exerts also relevant
      cardioprotective effects; hence, it has been proposed for the treatment of heart
      failure (HF). We tested the hypothesis that ghrelin can directly modulate cardiac
      energy substrate metabolism. METHODS AND RESULTS: We used chronically
      instrumented dogs, 8 with pacing-induced HF and 6 normal controls. Human des-acyl
      ghrelin [1.2 nmol/kg per hour] was infused intravenously for 15 minutes, followed
      by washout (rebaseline) and infusion of acyl ghrelin at the same dose. (3)H
      oleate and (14)C-glucose were coinfused and arterial and coronary sinus blood
      sampled to measure cardiac free fatty acid and glucose oxidation and lactate
      uptake. As expected, cardiac substrate metabolism was profoundly altered in HF
      because baseline oxidation levels of free fatty acids and glucose were,
      respectively, >70% lower and >160% higher compared with control. Neither des-acyl
      ghrelin nor acyl ghrelin significantly affected function and metabolism in normal
      hearts. However, in HF, des-acyl and acyl ghrelin enhanced myocardial oxygen
      consumption by 10.2+/-3.5% and 9.9+/-3.7%, respectively (P<0.05), and cardiac
      mechanical efficiency was not significantly altered. This was associated,
      respectively, with a 41.3+/-6.7% and 32.5+/-10.9% increase in free fatty acid
      oxidation and a 31.3+/-9.2% and 41.4+/-8.9% decrease in glucose oxidation (all
      P<0.05). CONCLUSIONS: Acute increases in des-acyl or acyl ghrelin do not
      interfere with cardiac metabolism in normal dogs, whereas they enhance free fatty
      acid oxidation and reduce glucose oxidation in HF dogs, thus partially correcting
      metabolic alterations in HF. This novel mechanism might contribute to the
      cardioprotective effects of ghrelin in HF.

PMID- 24855154
TI  - Insulin therapy in people with type 2 diabetes: opportunities and challenges?
AB  - Given the continued interest in defining the optimal management of individuals
      with type 2 diabetes, the Editor of Diabetes Care convened a working party of
      diabetes specialists to examine this topic in the context of insulin therapy.
      This was prompted by recent new evidence on the use of insulin in such people.
      The group was aware of evidence that the benefits of insulin therapy are still
      usually offered late, and thus the aim of the discussion was how to define the
      optimal timing and basis for decisions regarding insulin and to apply these
      concepts in practice. It was noted that recent evidence had built upon that of
      the previous decades, together confirming the benefits and safety of insulin
      therapy, albeit with concerns about the potential for hypoglycemia and gain in
      body weight. Insulin offers a unique ability to control hyperglycemia, being used
      from the time of diagnosis in some circumstances, when metabolic control is
      disturbed by medical illness, procedures, or therapy, as well as in the longer
      term in ambulatory care. For those previously starting insulin, various other
      forms of therapy can be added later, which offer complementary effects
      appropriate to individual needs. Here we review current evidence and
      circumstances in which insulin can be used, consider individualized choices of
      alternatives and combination regimens, and offer some guidance on personalized
      targets and tactics for glycemic control in type 2 diabetes. 

PMID- 24855156
TI  - Neurological consequences of diabetic ketoacidosis at initial presentation of
      type 1 diabetes in a prospective cohort study of children.
AB  - OBJECTIVE: To investigate the impact of new-onset diabetic ketoacidosis (DKA)
      during childhood on brain morphology and function. RESEARCH DESIGN AND METHODS:
      Patients aged 6-18 years with and without DKA at diagnosis were studied at four
      time points: <48 h, 5 days, 28 days, and 6 months postdiagnosis. Patients
      underwent magnetic resonance imaging (MRI) and spectroscopy with cognitive
      assessment at each time point. Relationships between clinical characteristics at
      presentation and MRI and neurologic outcomes were examined using multiple linear
      regression, repeated-measures, and ANCOVA analyses. RESULTS: Thirty-six DKA and
      59 non-DKA patients were recruited between 2004 and 2009. With DKA, cerebral
      white matter showed the greatest alterations with increased total white matter
      volume and higher mean diffusivity in the frontal, temporal, and parietal white
      matter. Total white matter volume decreased over the first 6 months. For gray
      matter in DKA patients, total volume was lower at baseline and increased over 6
      months. Lower levels of N-acetylaspartate were noted at baseline in the frontal
      gray matter and basal ganglia. Mental state scores were lower at baseline and at
      5 days. Of note, although changes in total and regional brain volumes over the
      first 5 days resolved, they were associated with poorer delayed memory recall and
      poorer sustained and divided attention at 6 months. Age at time of presentation
      and pH level were predictors of neuroimaging and functional outcomes.
      CONCLUSIONS: DKA at type 1 diabetes diagnosis results in morphologic and
      functional brain changes. These changes are associated with adverse
      neurocognitive outcomes in the medium term.

PMID- 24855158
TI  - Computer-based interventions to improve self-management in adults with type 2
      diabetes: a systematic review and meta-analysis.
AB  - OBJECTIVE: Structured patient education programs can reduce the risk of diabetes
      related complications. However, people appear to have difficulties attending face
      to-face education and alternatives are needed. This review looked at the impact
      of computer-based diabetes self-management interventions on health status,
      cardiovascular risk factors, and quality of life of adults with type 2 diabetes.
      RESEARCH DESIGN AND METHODS: We searched The Cochrane Library, Medline, Embase,
      PsycINFO, Web of Science, and CINAHL for relevant trials from inception to
      November 2011. Reference lists from relevant published studies were screened and
      authors contacted for further information when required. Two authors
      independently extracted relevant data using standard data extraction templates.
      RESULTS: Sixteen randomized controlled trials with 3,578 participants met the
      inclusion criteria. Interventions were delivered via clinics, the Internet, and
      mobile phones. Computer-based diabetes self-management interventions appear to
      have small benefits on glycemic control: the pooled effect on HbA1c was -0.2% (
      2.3 mmol/mol [95% CI -0.4 to -0.1%]). A subgroup analysis on mobile phone-based
      interventions showed a larger effect: the pooled effect on HbA1c from three
      studies was -0.50% (-5.46 mmol/mol [95% CI -0.7 to -0.3%]). There was no evidence
      of improvement in depression, quality of life, blood pressure, serum lipids, or
      weight. There was no evidence of significant adverse effects. CONCLUSIONS:
      Computer-based diabetes self-management interventions to manage type 2 diabetes
      appear to have a small beneficial effect on blood glucose control, and this
      effect was larger in the mobile phone subgroup. There was no evidence of benefit
      for other biological, cognitive, behavioral, or emotional outcomes.

PMID- 24855159
TI  - Insulin analogs-are they worth it? Yes!
AB  - The availability of insulin analogs has offered insulin replacement strategies
      that are proposed to more closely mimic normal human physiology. Specifically,
      there are a considerable number of reports demonstrating that prandial insulin
      analogs (lispro, aspart, glulisine) have pharmacokinetic and pharmacodynamic
      profiles closer to normal, with resulting faster onset and offset of insulin
      effect when compared with regular human insulin. In addition, basal insulin
      analogs (glargine, detemir) have been reported to offer longer duration of
      action, less variability, more predictability, less hypoglycemia (especially
      nocturnal), and a favorable effect on weight. However, an argument against use of
      analog insulins as compared with use of regular or NPH insulin is one that states
      that the effectiveness and risk of hypoglycemia are the only two valid clinical
      outcomes that should be used to compare the analog and human insulins. Thus,
      there remains a debate in some circles that analog insulins are no more effective
      than human insulins, yet at a much higher financial cost. To provide an in-depth
      understanding of both sides of the argument, we provide a discussion of this
      topic as part of this two-part point-counterpoint narrative. In the counterpoint
      narrative presented here, Dr. Davidson provides his argument and defends his
      opinion that outside of a few exceptions, analog insulins provide no clinical
      benefit compared with human insulins but cost much more. In the preceding point
      narrative, Dr. Grunberger provides a defense of analog insulins and their value
      in clinical management and suggests that when evaluating the "cost" of therapy, a
      much more global assessment is needed.

PMID- 24855157
TI  - Depression in adults in the T1D Exchange Clinic Registry.
AB  - OBJECTIVE: Little is known about the frequency of depression in adults with type
      1 diabetes (T1D) or its relationship to diabetes outcomes. The T1D Exchange
      clinic registry allowed us to explore depression in a large, heterogeneous
      sample. RESEARCH DESIGN AND METHODS: Participants >=18 years old (N = 6,172;
      median age 34 years; median diabetes duration 16 years; 55% female; and 89% non
      Hispanic white) completed the eight-item Patient Health Questionnaire (PHQ-8), a
      validated, reliable measure of current depression. Probable major depression was
      defined in four ways: PHQ-8 >=10, PHQ-8 >=12, per diagnostic algorithm, and as a
      continuous variable. Characteristics and clinical outcomes of those with and
      without depression were compared using logistic and linear regression models.
      RESULTS: A total of 4.6-10.3% of participants were classified as probable major
      depression depending on how defined. Participants classified as depressed were
      more likely female, nonwhite race/ethnicity, to have a lower household income and
      lower education level, to exercise less often, to miss insulin doses, and to have
      one or more complications (neuropathy, nephropathy, treatment for retinopathy, or
      cardiovascular/cerebrovascular disease) (all P < 0.01). HbA1c was higher in the
      depressed versus not depressed groups (8.4 +/- 1.7% [68 +/- 8.6 mmol/mol] vs. 7.8
      +/- 1.4% [62 +/- 15.3 mmol/mol]; P < 0.001). Occurrence of one or more diabetic
      ketoacidosis events (11 vs. 4%; P < 0.001) and one or more severe hypoglycemic
      events (18 vs. 9%; P < 0.001) in the past 3 months was higher among depressed
      participants. CONCLUSIONS: In the T1D Exchange clinic registry, adults with
      probable major depression have worse clinical outcomes than those not depressed.
      Whether identification and treatment of depression improves diabetes outcomes
      requires study. Depression is common in T1D, and better identification and
      treatment of this comorbid condition is needed.

PMID- 24855160
TI  - Insulin analogs--is there a compelling case to use them? No!
AB  - The availability of insulin analogs has offered insulin replacement strategies
      that are proposed to more closely mimic normal human physiology. Specifically,
      there are a considerable number of reports demonstrating that prandial insulin
      analogs (lispro, aspart, glulisine) have pharmacokinetic and pharmacodynamic
      profiles closer to normal, with resulting faster onset and offset of insulin
      effect when compared with regular human insulin. In addition, basal insulin
      analogs (glargine, detemir) have been reported to offer longer duration of
      action, less variability, more predictability, less hypoglycemia (especially
      nocturnal), and a favorable effect on weight. However, an argument against use of
      analog insulins as compared with use of regular or NPH insulin is one that states
      that the effectiveness and risk of hypoglycemia are the only two valid clinical
      outcomes that should be used to compare the analog and human insulins. Thus,
      there remains a debate in some circles that analog insulins are no more effective
      than human insulins, yet at a much higher financial cost. To provide an in-depth
      understanding of both sides of the argument, we provide a discussion of this
      topic as part of this two-part point-counterpoint narrative. In the counterpoint
      narrative presented here, Dr. Davidson provides his argument and defends his
      opinion that outside of a few exceptions, analog insulins provide no clinical
      benefit compared with human insulins but cost much more. In the preceding point
      narrative, Dr. Grunberger provides a defense of analog insulins and their value
      in clinical management and suggests that when evaluating the "cost" of therapy, a
      much more global assessment is needed.

PMID- 24855162
TI  - Pharmacokinetics of insulin aspart in pregnant women with type 1 diabetes: every
      day is different.

PMID- 24855163
TI  - Patient with iDEND syndrome-related mutation.

PMID- 24855164
TI  - Youth repeatedly hospitalized for DKA: proof of concept for novel interventions
      in children's healthcare (NICH).

PMID- 24855165
TI  - Optimizing insulin absorption and insulin injection technique in older adults.

PMID- 24855166
TI  - Diabetic charcot neuroarthropathy of the knee: conservative treatment options as
      alternatives to surgery: case reports of three patients.

PMID- 24855155
TI  - Impact of intensive lifestyle intervention on depression and health-related
      quality of life in type 2 diabetes: the Look AHEAD Trial.
AB  - OBJECTIVE: We examined the effects of an intensive lifestyle intervention (ILI),
      compared with a diabetes support and education (DSE) control intervention, on
      long-term changes in depression symptoms, antidepressant medication (ADM) use,
      and health-related quality of life (HRQoL) in overweight/obese individuals with
      type 2 diabetes. RESEARCH DESIGN AND METHODS: Look AHEAD was a multisite
      randomized controlled trial of 5,145 overweight/obese participants assigned to
      ILI (designed to produce weight loss) or DSE and followed for a median of 9.6
      years. The Beck Depression Inventory (BDI) was administered at baseline, annually
      at years 1-4, and again at year 8. Mean BDI scores and incidence of BDI scores
      >=10, indicative of likely mild or greater depression, were examined. Annually
      through year 10, participants reported their ADM use and completed the Medical
      Outcomes Study Short Form 36 (SF-36) questionnaire, which yields physical
      component summary (PCS) and mental component summary (MCS) scores. RESULTS: ILI
      significantly reduced the incidence of mild or greater depression symptoms (BDI
      scores >=10) compared with DSE (hazard ratio [HR] = 0.85; 95% CI 0.75-0.97; P =
      0.0145). Although SF-36 PCS scores worsened over time in both groups, ILI
      participants reported better physical function than DSE throughout the first 8
      years (all P values <0.01). There were no significant differences between
      treatment arms in the proportion of participants who used ADMs or in SF-36 MCS
      scores. CONCLUSIONS: ILI for overweight/obese patients with type 2 diabetes may
      reduce the risk of developing clinically significant symptoms of depression and
      preserve physical HRQoL. These findings should be considered when evaluating the
      potential benefits of ILIs.

PMID- 24855167
TI  - Association between serum total bilirubin levels and the morphology of corneal
      nerve fibers in Japanese patients with uncontrolled type 2 diabetes.

PMID- 24855168
TI  - Membership in a diabetes care network improves general practitioners' practices
      for HbA1c and microalbuminuria monitoring: a cohort study among patients with
      type 2 diabetes.

PMID- 24855169
TI  - Diagnostic confusion? Repeat HbA1c for the diagnosis of diabetes.

PMID- 24855170
TI  - Need for reclassification of diabetes secondary to iron overload in the ADA and
      WHO classifications.

PMID- 24855172
TI  - Improvement of electrophysiological neuropathy after islet transplantation for
      type 1 diabetes: a 5-year prospective study.

PMID- 24855171
TI  - Preventive measures for patients at risk for amputation from diabetes and
      peripheral arterial disease.

PMID- 24855173
TI  - Gestational diabetes mellitus: squaring the circle.

PMID- 24855174
TI  - Comment on Schmitz et al. Recurrent subthreshold depression in type 2 diabetes:
      an important risk factor for poor health outcomes. Diabetes care 2014;37:970-978.

PMID- 24855175
TI  - Response to comment on Schmitz et al. Recurrent subthreshold depression in type 2
      diabetes: an important risk factor for poor health outcomes. Diabetes care
      2014;37:970-978.

PMID- 24855176
TI  - Comment on Pepino et al. Sucralose affects glycemic and hormonal responses to an
      oral glucose load. Diabetes care 2013;36:2530-2535.

PMID- 24855177
TI  - Response to comment on Pepino et al. Sucralose affects glycemic and hormonal
      responses to an oral glucose load. Diabetes care 2013;36:2530-2535.

PMID- 24855178
TI  - Comment on Moore et al. Increased risk of cognitive impairment in patients with
      diabetes is associated with metformin. Diabetes care 2013;36:2981-2987.

PMID- 24855179
TI  - Response to comment on Moore et al. Increased risk of cognitive impairment in
      patients with diabetes is associated with metformin. Diabetes care 2013;36:2981
      2987.

PMID- 24855180
TI  - Comment on Hillis et al. The relative and combined ability of high-sensitivity
      cardiac troponin T and N-terminal pro-B-type natriuretic Peptide to predict
      cardiovascular events and death in patients with type 2 diabetes. Diabetes care
      2014;37:295-303.

PMID- 24855181
TI  - Response to comment on Hillis et al. The relative and combined ability of high
      sensitivity cardiac troponin T and N-terminal pro-B-type natriuretic Peptide to
      predict cardiovascular events and death in patients with type 2 diabetes.
      Diabetes care 2014;37:295-303.

PMID- 24855182
TI  - Comment on Lecoultre et al. Ten nights of moderate hypoxia improves insulin
      sensitivity in obese humans. Diabetes care 2013;36:e197-e198.

PMID- 24855183
TI  - Response to comment on Lecoultre et al. Ten nights of moderate hypoxia improves
      insulin sensitivity in obese humans. Diabetes care 2013;36:e197-e198.

PMID- 24855184
TI  - Evaluation of organic anion transporting polypeptide 1B1 and 1B3 humanized mice
      as a translational model to study the pharmacokinetics of statins.
AB  - Organic anion transporting polypeptide (Oatp) 1a/1b knockout and OATP1B1 and -1B3
      humanized mouse models are promising tools for studying the roles of these
      transporters in drug disposition. Detailed characterization of these models will
      help to better understand their utility for predicting clinical outcomes. To
      advance this approach, we carried out a comprehensive analysis of these mouse
      lines by evaluating the compensatory changes in mRNA expression, quantifying the
      amounts of OATP1B1 and -1B3 protein by liquid chromatography-tandem mass
      spectrometry, and studying the active uptake in isolated hepatocytes and the
      pharmacokinetics of some prototypical substrates including statins. Major
      outcomes from these studies were 1) mostly moderate compensatory changes in only
      a few genes involved in drug metabolism and disposition, 2) a robust hepatic
      expression of OATP1B1 and -1B3 proteins in the respective humanized mouse models,
      and 3) functional activities of the human transporters in hepatocytes isolated
      from the humanized models with several substrates tested in vitro and with
      pravastatin in vivo. However, the expression of OATP1B1 and -1B3 in the humanized
      models did not significantly alter liver or plasma concentrations of rosuvastatin
      and pitavastatin compared with Oatp1a/1b knockout controls under the conditions
      used in our studies. Hence, although the humanized OATP1B1 and -1B3 mice showed
      in vitro and/or in vivo functional activity with some statins, further
      characterization of these models is required to define their potential use and
      limitations in the prediction of drug disposition and drug-drug interactions in
      humans. 

PMID- 24855185
TI  - Hospital discharge recommendations can be confusing for people of low
      socioeconomic status, and difficult to follow due to constraints or conflicting
      personal goals.

PMID- 24855186
TI  - Review: intimate partner violence is associated with termination of pregnancy.

PMID- 24855187
TI  - Reason for CPXcitement in AML.

PMID- 24855188
TI  - Predicting treatment outcomes in CLL.

PMID- 24855189
TI  - Anergy: the CLL cell limbo.

PMID- 24855191
TI  - Splicing factor mutations in AML.

PMID- 24855190
TI  - Ibrutinib: targeting the hidden CLL.

PMID- 24855192
TI  - The iron fist: malaria and hepcidin.

PMID- 24855194
TI  - Anomalous systemic arterial supply to normal basal segments of the left lung
      without sequestration.

PMID- 24855195
TI  - Adeno-associated viruses as a method to induce atherosclerosis in mice and
      hamsters.

PMID- 24855193
TI  - Comparison between off-pump and on-pump coronary artery bypass grafting in
      patients with severe lesions at the circumflex artery territory: 5-year follow-up
      of the MASS III trial.
AB  - OBJECTIVES: The technical difficulty in the revascularization of the circumflex
      artery territory with off-pump surgery may compromise the outcome of this method
      in clinical follow-up. We aimed to evaluate cardiac events in patients with
      stable coronary artery disease and severe obstruction of the circumflex system,
      undergoing coronary artery bypass grafting (CABG) with or without cardiopulmonary
      bypass. METHODS: MASS III was a single-centre study that evaluated 308 patients
      with multivessel coronary artery disease randomized to on-pump (153) or off-pump
      (155) CABG. Of this total, 260 (84.4%) patients had, on coronary angiography, at
      least one 70% obstruction in the circumflex territory (141 on-pump and 119 off
      pump). The combined outcome was death, myocardial infarction, target vessel
      revascularization (angioplasty or surgery) or hospitalization for cardiac causes.
      Variables with possible associations (P < 0.1) were included in the multivariate
      analysis. RESULTS: The two groups were well matched for demographics and clinical
      and angiographic characteristics. After 5 years of follow-up, off-pump CABG had
      higher combined events than on-pump had: 25 (21%) vs 17 (12%), hazard ratio 1.88,
      95% confidence interval 1.02-3.48, P = 0.041. In the multivariate model with the
      inclusion of the following variables: age (P = 0.09) and complete
      revascularization (P = 0.68), off-pump surgery remained as a predictor of
      combined events in 5 years, P = 0.03. CONCLUSIONS: In patients with multivessel
      coronary artery disease and severe lesions in the circumflex territory, off-pump
      coronary artery bypass surgery resulted in a higher incidence of cardiac events
      at 5-year follow-up. CLINICAL TRIAL REGISTRATION NUMBER: ISRCTN59539154
      (http://www.controlled-trials.com).

PMID- 24855196
TI  - Myocardial repair around-the-clock.

PMID- 24855197
TI  - Copper futures: ceruloplasmin and heart failure.

PMID- 24855198
TI  - Apolipoprotein A-I and cholesterol efflux: the good, the bad, and the modified.

PMID- 24855199
TI  - B cells and humoral immunity in atherosclerosis.
AB  - Insights into the important contribution of inflammation and immune functions in
      the development and progression of atherosclerosis have greatly improved our
      understanding of this disease. Although the role of T cells has been extensively
      studied for decades, only recently has the role of B cells gained more attention.
      Recent studies have identified differential effects of different B-cell subsets
      and helped to clarify the still poorly understood mechanisms by which these act.
      B1 cells have been shown to prevent lesion formation, whereas B2 cells have been
      suggested to promote it. Natural IgM antibodies, mainly derived from B1 cells,
      have been shown to mediate atheroprotective effects, but the functional role of
      other immunoglobulin classes, particularly IgG, still remains elusive. In this
      review, we will focus on recent insights on the role of B cells and various
      immunoglobulin classes and how these may mediate their effects in atherosclerotic
      lesion formation. Moreover, we will highlight potential therapeutic approaches
      focusing on B-cell depletion that could be used to translate experimental
      evidence to human disease.

PMID- 24855201
TI  - Artery tertiary lymphoid organs contribute to innate and adaptive immune
      responses in advanced mouse atherosclerosis.
AB  - Tertiary lymphoid organs emerge in tissues in response to nonresolving
      inflammation. Recent research characterized artery tertiary lymphoid organs in
      the aorta adventitia of aged apolipoprotein E-deficient mice. The atherosclerosis
      associated lymphocyte aggregates are organized into distinct compartments,
      including separate T-cell areas harboring conventional, monocyte-derived,
      lymphoid, and plasmacytoid dendritic cells, as well as activated T-cell effectors
      and memory cells; B-cell follicles containing follicular dendritic cells in
      activated germinal centers; and peripheral niches of plasma cells. Artery
      tertiary lymphoid organs show marked neoangiogenesis, aberrant lymphangiogenesis,
      and extensive induction of high endothelial venules. Moreover, newly formed lymph
      node-like conduits connect the external lamina with high endothelial venules in T
      cell areas and also extend into germinal centers. Mouse artery tertiary lymphoid
      organs recruit large numbers of naive T cells and harbor lymphocyte subsets with
      opposing activities, including CD4(+) and CD8(+) effector and memory T cells,
      natural and induced CD4(+) regulatory T cells, and memory B cells at different
      stages of differentiation. These data suggest that artery tertiary lymphoid
      organs participate in primary immune responses and organize T- and B-cell
      autoimmune responses in advanced atherosclerosis. In this review, we discuss the
      novel concept that pro- and antiatherogenic immune responses toward unknown
      arterial wall-derived autoantigens may be organized by artery tertiary lymphoid
      organs and that disruption of the balance between pro- and antiatherogenic immune
      cell subsets may trigger clinically overt atherosclerosis.

PMID- 24855200
TI  - Mechanisms that regulate macrophage burden in atherosclerosis.
AB  - Mononuclear phagocytes (MPs) relevant to atherosclerosis include monocytes,
      macrophages, and dendritic cells. A decade ago, studies on macrophage behavior in
      atherosclerotic lesions were often limited to quantification of total macrophage
      area in cross-sections of plaques. Although technological advances are still
      needed to examine plaque MP populations in an increasingly dynamic and
      informative manner, innovative methods to interrogate the biology of MPs in
      atherosclerotic plaques developed in the past few years point to several
      mechanisms that regulate the accumulation and function of MPs within plaques.
      Here, I review the evolution of atherosclerotic plaques with respect to changes
      in the MP compartment from the initiation of plaque to its progression and
      regression, discussing the roles that recruitment, proliferation, and retention
      of MPs play at these different disease stages. Additional work in the future will
      be needed to better distinguish macrophages and dendritic cells in plaque and to
      address some basic unknowns in the field, including just how cholesterol drives
      accumulation of macrophages in lesions to build plaques in the first place and
      how macrophages as major effectors of innate immunity work together with
      components of the adaptive immune response to drive atherosclerosis. Answers to
      these questions are sought with the goal in mind of reversing disease where it
      exists and preventing its development where it does not.

PMID- 24855202
TI  - Cardiovascular actions of incretin-based therapies.
AB  - Glucagon-like peptide-1 receptor (GLP-1R) agonists and dipeptidyl peptidase-4
      (DPP-4) inhibitors represent 2 distinct classes of incretin-based therapies used
      for the treatment of type 2 diabetes mellitus. Activation of GLP-1R signaling or
      inhibition of DPP-4 activity produces a broad range of overlapping and unique
      cardiovascular actions. Native GLP-1 regulates cardiovascular biology via
      activation of the classical GLP-1R, or through GLP-1(9-36), a cardioactive
      metabolite generated by DPP-4-mediated cleavage. In contrast, clinically approved
      GLP-1R agonists are not cleaved to GLP-1(9-36) and produce the majority of their
      actions through the classical GLP-1R. The cardiovascular mechanisms engaged by
      DPP-4 inhibition are more complex, encompassing increased levels of intact GLP-1,
      reduced levels of GLP-1(9-36), and changes in levels of numerous cardioactive
      peptides. Herein we review recent experimental and clinical advances that reveal
      how GLP-1R agonists and DPP-4 inhibitors affect the normal and diabetic heart and
      coronary vasculature, often independent of changes in blood glucose. Improved
      understanding of the complex science of incretin-based therapies is required to
      optimize the selection of these therapeutic agents for the treatment of diabetic
      patients with cardiovascular disease.

PMID- 24855203
TI  - The autonomic nervous system and hypertension.
AB  - Physiological studies have long documented the key role played by the autonomic
      nervous system in modulating cardiovascular functions and in controlling blood
      pressure values, both at rest and in response to environmental stimuli.
      Experimental and clinical investigations have tested the hypothesis that the
      origin, progression, and outcome of human hypertension are related to
      dysfunctional autonomic cardiovascular control and especially to abnormal
      activation of the sympathetic division. Here, we review the recent literature on
      the adrenergic and vagal abnormalities that have been reported in essential
      hypertension, with emphasis on their role as promoters and as amplifiers of the
      high blood pressure state. We also discuss the possible mechanisms underlying
      these abnormalities and their importance in the development and progression of
      the structural and functional cardiovascular damage that characterizes
      hypertension. Finally, we examine the modifications of sympathetic and vagal
      cardiovascular influences induced by current nonpharmacological and
      pharmacological interventions aimed at correcting elevations in blood pressure
      and restoring the normotensive state.

PMID- 24855204
TI  - The autonomic nervous system and heart failure.
AB  - The pathophysiology of heart failure (HF) is characterized by hemodynamic
      abnormalities that result in neurohormonal activation and autonomic imbalance
      with increase in sympathetic activity and withdrawal of vagal activity.
      Alterations in receptor activation from this autonomic imbalance may have
      profound effects on cardiac function and structure. Inhibition of the sympathetic
      drive to the heart through beta-receptor blockade has become a standard component
      of therapy for HF with a dilated left ventricle because of its effectiveness in
      inhibiting the ventricular structural remodeling process and in prolonging life.
      Several devices for selective modulation of sympathetic and vagal activity have
      recently been developed in an attempt to alter the natural history of HF. The
      optimal counteraction of the excessive sympathetic activity is still unclear. A
      profound decrease in adrenergic support with excessive blockade of the
      sympathetic nervous system may result in adverse outcomes in clinical HF. In this
      review, we analyze the data supporting a contributory role of the autonomic
      functional alterations on the course of HF, the techniques used to assess
      autonomic nervous system activity, the evidence for clinical effectiveness of
      pharmacological and device interventions, and the potential future role of
      autonomic nervous system modifiers in the management of this syndrome.

PMID- 24855205
TI  - Adeno-associated virus vectors as therapeutic and investigational tools in the
      cardiovascular system.
AB  - The use of vectors based on the small parvovirus adeno-associated virus has
      gained significant momentum during the past decade. Their high efficiency of
      transduction of postmitotic tissues in vivo, such as heart, brain, and retina,
      renders these vectors extremely attractive for several gene therapy applications
      affecting these organs. Besides functional correction of different monogenic
      diseases, the possibility to drive efficient and persistent transgene expression
      in the heart offers the possibility to develop innovative therapies for prevalent
      conditions, such as ischemic cardiomyopathy and heart failure. Therapeutic genes
      are not only restricted to protein-coding complementary DNAs but also include
      short hairpin RNAs and microRNA genes, thus broadening the spectrum of possible
      applications. In addition, several spontaneous or engineered variants in the
      virus capsid have recently improved vector efficiency and expanded their tropism.
      Apart from their therapeutic potential, adeno-associated virus vectors also
      represent outstanding investigational tools to explore the function of individual
      genes or gene combinations in vivo, thus providing information that is
      conceptually similar to that obtained from genetically modified animals. Finally,
      their single-stranded DNA genome can drive homology-directed gene repair at high
      efficiency. Here, we review the main molecular characteristics of adeno
      associated virus vectors, with a particular view to their applications in the
      cardiovascular field.

PMID- 24855207
TI  - Smac mimetic and glucocorticoids synergize to induce apoptosis in childhood ALL
      by promoting ripoptosome assembly.
AB  - Apoptosis resistance contributes to poor outcome in pediatric acute lymphoblastic
      leukemia (ALL). Here, we identify a novel synergistic combination of Smac mimetic
      BV6 and glucocorticoids (GCs) (ie, dexamethasone, prednisolone) to trigger
      apoptosis in ALL cells. BV6 and GCs similarly cooperate to induce apoptosis in
      patient-derived leukemia samples, underlining the clinical relevance.
      Importantly, BV6/dexamethasone cotreatment is significantly more effective than
      monotherapy to delay leukemia growth in a patient-derived xenograft model of
      pediatric ALL without causing additional side effects. In contrast, BV6 does not
      increase cytotoxicity of dexamethasone against nonmalignant peripheral blood
      lymphocytes, mesenchymal stromal cells, and CD34-positive hematopoietic cells. We
      identify a novel mechanism by showing that BV6 and dexamethasone cooperate to
      deplete cIAP1, cIAP2, and XIAP, thereby promoting assembly of the ripoptosome, a
      RIP1/FADD/caspase-8-containing complex. This complex is critical and is required
      for BV6/dexamethasone-induced cell death, because RIP1 knockdown reduces caspase
      activation, reactive oxygen species production, and cell death. Ripoptosome
      formation occurs independently of autocrine/paracrine loops of death receptor
      ligands, because blocking antibodies for TNFalpha, tumor necrosis factor-related
      apoptosis-inducing ligand, or CD95 ligand or knockdown of death receptors fail to
      rescue BV6/dexamethasone-induced cell death. This is the first report showing
      that BV6 sensitizes for GC-triggered cell death by promoting ripoptosome
      formation with important implications for apoptosis-targeted therapies of ALL. 

PMID- 24855206
TI  - Lowest numbers of primary CD8(+) T cells can reconstitute protective immunity
      upon adoptive immunotherapy.
AB  - Patients undergoing allogeneic hematopoietic stem cell transplantation (allo
      HSCT) are threatened by potentially lethal viral manifestations like
      cytomegalovirus (CMV) reactivation. Because the success of today's virostatic
      treatment is limited by side effects and resistance development, adoptive
      transfer of virus-specific memory T cells derived from the stem cell donor has
      been proposed as an alternative therapeutic strategy. In this context, dose
      minimization of adoptively transferred T cells might be warranted for the
      avoidance of graft-versus-host disease (GVHD), in particular in prophylactic
      settings after T-cell-depleting allo-HSCT protocols. To establish a lower limit
      for successful adoptive T-cell therapy, we conducted low-dose CD8(+) T-cell
      transfers in the well-established murine Listeria monocytogenes (L.m.) infection
      model. Major histocompatibility complex-Streptamer-enriched antigen-specific
      CD62L(hi) but not CD62L(lo) CD8(+) memory T cells proliferated, differentiated,
      and protected against L.m. infections after prophylactic application. Even
      progenies derived from a single CD62L(hi) L.m.-specific CD8(+) T cell could be
      protective against bacterial challenge. In analogy, low-dose transfers of
      Streptamer-enriched human CMV-specific CD8(+) T cells into allo-HSCT recipients
      led to strong pathogen-specific T-cell expansion in a compassionate-use setting.
      In summary, low-dose adoptive T-cell transfer (ACT) could be a promising
      strategy, particularly for prophylactic treatment of infectious complications
      after allo-HSCT. 

PMID- 24855208
TI  - SIRT1 prevents genotoxic stress-induced p53 activation in acute myeloid leukemia.
AB  - SIRT1 is an important regulator of cellular stress response and genomic
      integrity. Its role in tumorigenesis is controversial. Whereas sirtuin 1 (SIRT1)
      can act as a tumor suppressor in some solid tumors, increased expression has been
      demonstrated in many cancers, including hematologic malignancies. In chronic
      myeloid leukemia, SIRT1 promoted leukemia development, and targeting SIRT1
      sensitized chronic myeloid leukemia progenitors to tyrosine kinase inhibitor
      treatment. In this study, we investigated the role of SIRT1 in acute myeloid
      leukemia (AML). We show that SIRT1 protein, but not RNA levels, is overexpressed
      in AML samples harboring activating mutations in signaling pathways. In FMS-like
      tyrosine kinase 3-internal tandem duplication (FLT3-ITD)(+)-cells protein,
      expression of SIRT1 is regulated by FLT3 kinase activity. In addition, SIRT1
      function is modulated via the ATM-DBC1-SIRT1 axis in a FLT3-ITD-dependent manner.
      In murine leukemia models driven by MLL-AF9 or AML1-ETO coexpressing FLT3-ITD,
      SIRT1 acts as a safeguard to counteract oncogene-induced stress, and leukemic
      blasts become dependent on SIRT1 activity. Pharmacologic targeting or RNAi
      mediated knockdown of SIRT1 inhibited cell growth and sensitized AML cells to
      tyrosine kinase inhibitor treatment and chemotherapy. This effect was a result of
      the restoration of p53 activity. Our data suggest that targeting SIRT1 represents
      an attractive therapeutic strategy to overcome primary resistance in defined
      subsets of patients with AML. 

PMID- 24855209
TI  - Translocation t(2;11) in CLL cells results in CXCR4/MAML2 fusion oncogene.
AB  - Recent investigations of chromosomal aberrations in chronic lymphocytic leukemia
      (CLL) led to a better understanding of the molecular causes of CLL. Here we
      report a rearrangement between MAML2 (mastermind-like protein 2) and CXCR4
      (specific receptor for CXC chemokine stromal cell-derived factor-1) in CLL cells
      of a patient with a t(2;11)(q22.1;q21) chromosomal translocation. The
      rearrangement between MAML2 and CXCR4, created by a t(2;11)(q22.1;q21)
      translocation, results in a new fusion gene in which a portion of CXCR4 is linked
      to the MAML2 gene. This fusion gene encodes for CXCR4/MAML2 protein chimera in
      which the N-terminal basic domain of MAML2 is replaced by the N-terminal domain
      of CXCR4. 

PMID- 24855210
TI  - Activated innate lymphoid cells are associated with a reduced susceptibility to
      graft-versus-host disease.
AB  - Allogeneic hematopoietic stem cell transplantation (HSCT) is widely used to treat
      hematopoietic cell disorders but is often complicated by graft-versus-host
      disease (GVHD), which causes severe epithelial damage. Here we have investigated
      longitudinally the effects of induction chemotherapy, conditioning
      radiochemotherapy, and allogeneic HSCT on composition, phenotype, and recovery of
      circulating innate lymphoid cells (ILCs) in 51 acute leukemia patients. We found
      that reconstitution of ILC1, ILC2, and NCR(-)ILC3 was slow compared with that of
      neutrophils and monocytes. NCR(+) ILC3 cells, which are not present in the
      circulation of healthy persons, appeared both after induction chemotherapy and
      after allogeneic HSCT. Circulating patient ILCs before transplantation, as well
      as donor ILCs after transplantation, expressed activation (CD69), proliferation
      (Ki-67), and tissue homing markers for gut (alpha4beta7, CCR6) and skin (CCR10
      and CLA). The proportion of ILCs expressing these markers was associated with a
      decreased susceptibility to therapy-induced mucositis and acute GVHD. Taken
      together, these data suggest that ILC recovery and treatment-related tissue
      damage are interrelated and affect the development of GVHD. 

PMID- 24855211
TI  - Impact of FLT3(ITD) mutant allele level on relapse risk in intermediate-risk
      acute myeloid leukemia.
AB  - Some studies have suggested that cases of acute myeloid leukemia (AML) with low
      levels of FLT3 internal tandem duplications (FLT3(ITD)) do not have a worse
      prognosis if there is a concomitant NPM1 mutation, although this is
      controversial. To clarify this therapeutically important issue, we have analyzed
      FLT3(ITD) and NPM1(MUT) levels in 1609 younger adult cases of cytogenetically
      intermediate-risk AML. The cumulative incidence of relapse was increased in
      NPM1(MUT) cases by the presence of a FLT3(ITD), but did not differ markedly
      according to FLT3(ITD) level. This remained true when allowance was made for poor
      leukemic cell purity by adjustment of the FLT3(ITD) level to the measured
      NPM1(MUT) level. If consolidation therapies are to be determined by relapse risk,
      then NPM1(MUT) cases with low-level FLT3(ITD) should not be considered as good
      risk without further studies. AML 12 and AML 15 are registered at
      http://www.controlled-trials.com under ISRCTN17833622 and ISRCTN17161961,
      respectively. 

PMID- 24855213
TI  - Helical flow pattern in the right pulmonary artery after Fontan palliation.

PMID- 24855214
TI  - Quantitative assessment of primary mitral regurgitation using left ventricular
      volumes: a three-dimensional transthoracic echocardiographic pilot study.
AB  - AIMS: To investigate the value of assessment of mitral regurgitant fraction (RF)
      using left ventricular (LV) volumes obtained by three-dimensional
      echocardiography (3DE) to quantify primary mitral regurgitation (MR). METHODS AND
      RESULTS: Sixty patients with primary MR in sinus rhythm were prospectively
      enrolled. RF was calculated using either 2DE or 3DE LV volumes obtained as
      follows: (LV total stroke volume - LV forward stroke volume by Doppler)/LV total
      stroke volume. Severity of MR was graded independently by two cardiologists
      blinded to LV volumetric data using an integrative approach, as recommended by
      current guidelines. Sixty patients with LV ejection fraction >50% and no MR were
      also studied. In patients without MR, 3D total LV stroke volume was more strongly
      correlated with LV forward stroke volume than 2D total LV stroke volume (r =
      0.75, P < 0.0001 vs. r = 0.62, P < 0.0001, respectively). The 3D method had a
      feasibility of 90% in patients with MR. Inter-reader concordance for MR grading
      (four grades) was excellent with a Kappa-value of 0.90, P < 0.0001. A significant
      correlation was observed between grade of MR severity and 3D RF (r = 0.83, P <
      0.0001) and 2D RF (r = 0.74, P < 0.0001). Comparisons between individual grades
      for 3D RF were significant (P < 0.05) except for 3+ vs. 4+ MR (P = 0.213). All
      patients with 3D RF >=40% had >=3+ or 4+ MR and those with 3D RF <=30% had 1+ or
      2+ MR with a 'grey' overlap zone between 30 and 40%. CONCLUSIONS: RF can be
      routinely determined using 3D LV volumes with a high feasibility in patients with
      primary MR and is reliable for identification of Grade 3+ or Grade 4+ MR. The
      incorporation of this parameter into the currently recommended multiparametric
      integrative approach might be helpful to discriminate significant MR.

PMID- 24855212
TI  - Carfilzomib, cyclophosphamide, and dexamethasone in patients with newly diagnosed
      multiple myeloma: a multicenter, phase 2 study.
AB  - This multicenter, open-label phase 2 trial determined the safety and efficacy of
      carfilzomib, a novel and irreversible proteasome inhibitor, in combination with
      cyclophosphamide and dexamethasone (CCyd) in patients with newly diagnosed
      multiple myeloma (NDMM) >=65 years of age or who were ineligible for autologous
      stem cell transplantation. Patients (N = 58) received CCyd for up to 9 28-day
      cycles, followed by maintenance with carfilzomib until progression or
      intolerance. After a median of 9 CCyd induction cycles (range 1-9), 95% of
      patients achieved at least a partial response, 71% achieved at least a very good
      partial response, 49% achieved at least a near complete response, and 20%
      achieved stringent complete response. After a median follow-up of 18 months, the
      2-year progression-free survival and overall survival rates were 76% and 87%,
      respectively. The most frequent grade 3 to 5 toxicities were neutropenia (20%),
      anemia (11%), and cardiopulmonary adverse events (7%). Peripheral neuropathy was
      limited to grades 1 and 2 (9%). Fourteen percent of patients discontinued
      treatment because of adverse events, and 21% of patients required carfilzomib
      dose reductions. In summary, results showed high complete response rates and a
      good safety profile. This trial was registered at clinicaltrials.gov as
      #NCT01346787. 

PMID- 24855215
TI  - Effects of percutaneous closure of atrial septal defect on left atrial mechanical
      and conduction functions.
AB  - AIMS: Atrial septal defect (ASD) is one of the most common congenital heart
      diseases in adults. We prospectively evaluated early and mid-term effects of the
      percutaneous closure of secundum ASD on atrial electromechanical delay (AEMD) and
      left atrial (LA) mechanical functions at the first day and sixth month in
      patients undergoing percutaneous closure. METHODS AND RESULTS: Forty-one patients
      were included in this study. Twenty-six (63.4%) of the 41 patients were female
      and the mean age was 41 +/- 13 years. All the patients had echocardiographic
      examination before the procedure and at the first day and sixth month after the
      procedure. LA volumes (maximal, minimal, and presystolic) and EMD (lateral,
      septal, and tricuspid) were measured. Left and right intra- and inter-AEMD were
      not changed at the first day but both were significantly shorter at the sixth
      month. There was no change in the total emptying volume and fraction before and
      after the procedure. LA maximal, minimal, and pre-systolic volumes, active
      emptying volume, and fractions were decreased at the first day and at the sixth
      month compared with pre-procedural volumes. LA passive emptying volume, passive
      emptying fraction, and conduit volume were increased at the first day and at the
      sixth month compared with pre-procedural volumes. CONCLUSION: Our results
      revealed that there was no change in the LA mechanical reservoir functions, but
      improved conduit function and impaired contractility functions early and in the
      mid-term after percutaneous closure of ASD and decreased AEMD only in the mid
      term.

PMID- 24855216
TI  - The year 2013 in the European Heart Journal--Cardiovascular Imaging: Part II.
AB  - The new multi-modality cardiovascular imaging journal, European Heart Journal -
      Cardiovascular Imaging, was created in 2012. Here we summarize the most important
      studies from the journal's second year in two articles. Part I of the review has
      summarized studies in myocardial function, myocardial ischaemia, and emerging
      techniques in cardiovascular imaging. Part II is focussed on valvular heart
      diseases, heart failure, cardiomyopathies, and congenital heart diseases. 

PMID- 24855217
TI  - The year 2013 in the European Heart Journal--Cardiovascular Imaging. Part I.
AB  - The new multimodality cardiovascular imaging journal, European Heart Journal -
      Cardiovascular Imaging, was created in 2012. Here, we summarize the most
      important studies from the journal's second year in two articles. Part I of the
      review will focus on studies in myocardial function, myocardial ischaemia, and
      emerging techniques in cardiovascular imaging, and Part II will focus on valvular
      heart diseases, heart failure, cardiomyopathies, and congenital heart diseases. 

PMID- 24855218
TI  - T1 mapping - beware regional variations.

PMID- 24855219
TI  - An interesting case of an absent right-sided AV connection with an
      atrioventricular septal defect and double-outlet left atrium.

PMID- 24855220
TI  - Update of the European Association of Cardiovascular Imaging (EACVI) Core
      Syllabus for the European Cardiovascular Magnetic Resonance Certification Exam.
AB  - An updated version of the European Association of Cardiovascular Imaging (EACVI)
      Core Syllabus for the European Cardiovascular Magnetic Resonance (CMR)
      Certification Exam is now available online. The syllabus lists key elements of
      knowledge in CMR. It represents a framework for the development of training
      curricula and provides expected knowledge-based learning outcomes to the CMR
      trainees, in particular those intending to demonstrate CMR knowledge in the
      European CMR exam, a core requirement in the CMR certification process. 

PMID- 24855222
TI  - Appointment of new JVDI editors.

PMID- 24855221
TI  - New mothers are most likely to be depressed four years after giving birth.

PMID- 24855223
TI  - Intraerythrocytic iridovirus in central bearded dragons (Pogona vitticeps).
AB  - Three adult central bearded dragons (Pogona vitticeps) originating from a
      commercial breeding facility presented with clinical signs, including anorexia,
      dehydration, white multifocal lesions on the dorsal aspect of the tongue,
      blepharospasm, and weight loss. In 1 of 3 lizards, a marked regenerative anemia
      was noted, and all 3 bearded dragons had erythrocytic intracytoplasmic inclusion
      bodies. Nine bearded dragons housed in contact also had identical, but fewer
      intraerythrocytic inclusions. Inclusion bodies examined by electron microscopy
      had particles consistent with iridoviruses. Attempts to culture the virus were
      unsuccessful; however, amplification and sequencing of regions of the viral DNA
      polymerase by polymerase chain reaction confirmed the presence of an iridovirus.
      One of the bearded dragons died, while the 2 others showing clinical signs were
      euthanized. The remaining 9 infected bearded dragons of the teaching colony were
      also euthanized. Postmortem examination revealed a moderate, multifocal,
      lymphoplasmacytic or mononuclear adenitis of the tongue in the 3 bearded dragons,
      and a lymphohistiocytic hepatitis with bacterial granulomas in 2 lizards.

PMID- 24855224
TI  - Epithelial regeneration and cancer: news from the Src front.

PMID- 24855225
TI  - Evaluating environmental impacts of alternative construction waste management
      approaches using supply-chain-linked life-cycle analysis.
AB  - Waste management in construction is critical for the sustainable treatment of
      building-related construction and demolition (C&D) waste materials, and recycling
      of these wastes has been considered as one of the best strategies in minimization
      of C&D debris. However, recycling of C&D materials may not always be a feasible
      strategy for every waste type and therefore recycling and other waste treatment
      strategies should be supported by robust decision-making models. With the aim of
      assessing the net carbon, energy, and water footprints of C&D recycling and other
      waste management alternatives, a comprehensive economic input-output-based hybrid
      life-cycle assessment model is developed by tracing all of the economy-wide
      supply-chain impacts of three waste management strategies: recycling,
      landfilling, and incineration. Analysis results showed that only the recycling of
      construction materials provided positive environmental footprint savings in terms
      of carbon, energy, and water footprints. Incineration is a better option as a
      secondary strategy after recycling for water and energy footprint categories,
      whereas landfilling is found to be as slightly better strategy when carbon
      footprint is considered as the main focus of comparison. In terms of construction
      materials' environmental footprint, nonferrous metals are found to have a
      significant environmental footprint reduction potential if recycled. 

PMID- 24855226
TI  - A new look.

PMID- 24855227
TI  - Inevitable inequality?

PMID- 24855231
TI  - Planetary science. NASA planners gear up for martian sample return.

PMID- 24855233
TI  - Cosmology. Blockbuster claim could collapse in a cloud of dust.

PMID- 24855232
TI  - Psychology. Replication effort provokes praise--and 'bullying' charges.

PMID- 24855234
TI  - Research funding. Doing the math in Berlin.

PMID- 24855235
TI  - Australia. Southern sky dims.

PMID- 24855236
TI  - A lonely crusade.

PMID- 24855237
TI  - Oceans. Lamarck was partially right--and that is good for corals.

PMID- 24855238
TI  - Geophysics. Deep mantle matters.

PMID- 24855239
TI  - Cancer immunology. Identifying the infiltrators.

PMID- 24855240
TI  - Atmospheric science. Record-breaking winters and global climate change.

PMID- 24855241
TI  - Medicine. A unified cause for adrenal Cushing's syndrome.

PMID- 24855242
TI  - Cosmology. Testing gauge/gravity duality on a quantum black hole.

PMID- 24855243
TI  - Translational genomics. Targeting the host immune response to fight infection.

PMID- 24855244
TI  - Sociology of science. "Undemocracy": inequalities in science.

PMID- 24855247
TI  - Specimen collection: an essential tool--response.

PMID- 24855246
TI  - Specimen collection: plan for the future.

PMID- 24855249
TI  - The science of inequality. What the numbers tell us. Introduction.

PMID- 24855250
TI  - A world of difference.

PMID- 24855251
TI  - The ancient roots of the 1%.

PMID- 24855252
TI  - Our egalitarian Eden.

PMID- 24855253
TI  - Tax man's gloomy message: the rich will get richer.

PMID- 24855254
TI  - Physicists say it's simple.

PMID- 24855255
TI  - Can disparities be deadly?

PMID- 24855245
TI  - Specimen collection: an essential tool.

PMID- 24855256
TI  - While emerging economies boom, equality goes bust.

PMID- 24855257
TI  - Tracking who climbs up--and who falls down--the ladder.

PMID- 24855258
TI  - Inequality in the long run.
AB  - This Review presents basic facts regarding the long-run evolution of income and
      wealth inequality in Europe and the United States. Income and wealth inequality
      was very high a century ago, particularly in Europe, but dropped dramatically in
      the first half of the 20th century. Income inequality has surged back in the
      United States since the 1970s so that the United States is much more unequal than
      Europe today. We discuss possible interpretations and lessons for the future. 

PMID- 24855259
TI  - Skills, education, and the rise of earnings inequality among the "other 99
      percent".
AB  - The singular focus of public debate on the "top 1 percent" of households
      overlooks the component of earnings inequality that is arguably most
      consequential for the "other 99 percent" of citizens: the dramatic growth in the
      wage premium associated with higher education and cognitive ability. This Review
      documents the central role of both the supply and demand for skills in shaping
      inequality, discusses why skill demands have persistently risen in industrialized
      countries, and considers the economic value of inequality alongside its potential
      social costs. I conclude by highlighting the constructive role for public policy
      in fostering skills formation and preserving economic mobility. 

PMID- 24855260
TI  - Income inequality in the developing world.
AB  - Should income inequality be of concern in developing countries? New data reveal
      less income inequality in the developing world than 30 years ago. However, this
      is due to falling inequality between countries. Average inequality within
      developing countries has been slowly rising, though staying fairly flat since
      2000. As a rule, higher rates of growth in average incomes have not put upward
      pressure on inequality within countries. Growth has generally helped reduce the
      incidence of absolute poverty, but less so in more unequal countries. High
      inequality also threatens to stall future progress against poverty by attenuating
      growth prospects. Perceptions of rising absolute gaps in living standards between
      the rich and the poor in growing economies are also consistent with the evidence.

PMID- 24855262
TI  - On the psychology of poverty.
AB  - Poverty remains one of the most pressing problems facing the world; the
      mechanisms through which poverty arises and perpetuates itself, however, are not
      well understood. Here, we examine the evidence for the hypothesis that poverty
      may have particular psychological consequences that can lead to economic
      behaviors that make it difficult to escape poverty. The evidence indicates that
      poverty causes stress and negative affective states which in turn may lead to
      short-sighted and risk-averse decision-making, possibly by limiting attention and
      favoring habitual behaviors at the expense of goal-directed ones. Together, these
      relationships may constitute a feedback loop that contributes to the perpetuation
      of poverty. We conclude by pointing toward specific gaps in our knowledge and
      outlining poverty alleviation programs that this mechanism suggests. 

PMID- 24855261
TI  - The intergenerational transmission of inequality: maternal disadvantage and
      health at birth.
AB  - Health at birth is an important predictor of long-term outcomes, including
      education, income, and disability. Recent evidence suggests that maternal
      disadvantage leads to worse health at birth through poor health behaviors;
      exposure to harmful environmental factors; worse access to medical care,
      including family planning; and worse underlying maternal health. With increasing
      inequality, those at the bottom of the distribution now face relatively worse
      economic conditions, but newborn health among the most disadvantaged has actually
      improved. The most likely explanation is increasing knowledge about determinants
      of infant health and how to protect it along with public policies that put this
      knowledge into practice. 

PMID- 24855264
TI  - Disproportionation of (Mg,Fe)SiO3 perovskite in Earth's deep lower mantle.
AB  - The mineralogical constitution of the Earth's mantle dictates the geophysical and
      geochemical properties of this region. Previous models of a perovskite-dominant
      lower mantle have been built on the assumption that the entire lower mantle down
      to the top of the D" layer contains ferromagnesian silicate [(Mg,Fe)SiO3] with
      nominally 10 mole percent Fe. On the basis of experiments in laser-heated diamond
      anvil cells, at pressures of 95 to 101 gigapascals and temperatures of 2200 to
      2400 kelvin, we found that such perovskite is unstable; it loses its Fe and
      disproportionates to a nearly Fe-free MgSiO3 perovskite phase and an Fe-rich
      phase with a hexagonal structure. This observation has implications for enigmatic
      seismic features beyond ~2000 kilometers depth and suggests that the lower mantle
      may contain previously unidentified major phases. 

PMID- 24855265
TI  - Real-space imaging of molecular structure and chemical bonding by single-molecule
      inelastic tunneling probe.
AB  - The arrangement of atoms and bonds in a molecule influences its physical and
      chemical properties. The scanning tunneling microscope can provide electronic and
      vibrational signatures of single molecules. However, these signatures do not
      relate simply to the molecular structure and bonding. We constructed an inelastic
      tunneling probe based on the scanning tunneling microscope to sense the local
      potential energy landscape of an adsorbed molecule with a carbon monoxide (CO)
      terminated tip. The skeletal structure and bonding of the molecule are revealed
      from imaging the spatial variations of a CO vibration as the CO-terminated tip
      probes the core of the interactions between adjacent atoms. An application of the
      inelastic tunneling probe reveals the sharing of hydrogen atoms among multiple
      centers in intramolecular and extramolecular bonding. 

PMID- 24855266
TI  - Melting of subducted basalt at the core-mantle boundary.
AB  - The geological materials in Earth's lowermost mantle control the characteristics
      and interpretation of seismic ultra-low velocity zones at the base of the core
      mantle boundary. Partial melting of the bulk lower mantle is often advocated as
      the cause, but this does not explain the nonubiquitous character of these
      regional seismic features. We explored the melting properties of mid-oceanic
      ridge basalt (MORB), which can reach the lowermost mantle after subduction of
      oceanic crust. At a pressure representative of the core-mantle boundary (135
      gigapascals), the onset of melting occurs at ~3800 kelvin, which is ~350 kelvin
      below the mantle solidus. The SiO2-rich liquid generated either remains trapped
      in the MORB material or solidifies after reacting with the surrounding MgO-rich
      mantle, remixing subducted MORB with the lowermost mantle. 

PMID- 24855263
TI  - Antibodies to PfSEA-1 block parasite egress from RBCs and protect against malaria
      infection.
AB  - Novel vaccines are urgently needed to reduce the burden of severe malaria. Using
      a differential whole-proteome screening method, we identified Plasmodium
      falciparum schizont egress antigen-1 (PfSEA-1), a 244-kilodalton parasite antigen
      expressed in schizont-infected red blood cells (RBCs). Antibodies to PfSEA-1
      decreased parasite replication by arresting schizont rupture, and conditional
      disruption of PfSEA-1 resulted in a profound parasite replication defect.
      Vaccination of mice with recombinant Plasmodium berghei PbSEA-1 significantly
      reduced parasitemia and delayed mortality after lethal challenge with the
      Plasmodium berghei strain ANKA. Tanzanian children with antibodies to recombinant
      PfSEA-1A (rPfSEA-1A) did not experience severe malaria, and Kenyan adolescents
      and adults with antibodies to rPfSEA-1A had significantly lower parasite
      densities than individuals without these antibodies. By blocking schizont egress,
      PfSEA-1 may synergize with other vaccines targeting hepatocyte and RBC invasion. 

PMID- 24855267
TI  - Ancient DNA reveals elephant birds and kiwi are sister taxa and clarifies ratite
      bird evolution.
AB  - The evolution of the ratite birds has been widely attributed to vicariant
      speciation, driven by the Cretaceous breakup of the supercontinent Gondwana. The
      early isolation of Africa and Madagascar implies that the ostrich and extinct
      Madagascan elephant birds (Aepyornithidae) should be the oldest ratite lineages.
      We sequenced the mitochondrial genomes of two elephant birds and performed
      phylogenetic analyses, which revealed that these birds are the closest relatives
      of the New Zealand kiwi and are distant from the basal ratite lineage of
      ostriches. This unexpected result strongly contradicts continental vicariance and
      instead supports flighted dispersal in all major ratite lineages. We suggest that
      convergence toward gigantism and flightlessness was facilitated by early Tertiary
      expansion into the diurnal herbivory niche after the extinction of the dinosaurs.

PMID- 24855268
TI  - FoxP influences the speed and accuracy of a perceptual decision in Drosophila.
AB  - Decisions take time if information gradually accumulates to a response threshold,
      but the neural mechanisms of integration and thresholding are unknown. We
      characterized a decision process in Drosophila that bears the behavioral
      signature of evidence accumulation. As stimulus contrast in trained odor
      discriminations decreased, reaction times increased and perceptual accuracy
      declined, in quantitative agreement with a drift-diffusion model. FoxP mutants
      took longer than wild-type flies to form decisions of similar or reduced
      accuracy, especially in difficult, low-contrast tasks. RNA interference with FoxP
      expression in alphabeta core Kenyon cells, or the overexpression of a potassium
      conductance in these neurons, recapitulated the FoxP mutant phenotype. A mushroom
      body subdomain whose development or function require the transcription factor
      FoxP thus supports the progression of a decision toward commitment. 

PMID- 24855269
TI  - Rapid Hebbian axonal remodeling mediated by visual stimulation.
AB  - We examined how correlated firing controls axon remodeling, using in vivo time
      lapse imaging and electrophysiological analysis of individual retinal ganglion
      cell (RGC) axons that were visually stimulated either synchronously or
      asynchronously relative to neighboring inputs in the Xenopus laevis optic tectum.
      RGCs stimulated out of synchrony rapidly lost the ability to drive tectal
      postsynaptic partners while their axons grew and added many new branches. In
      contrast, synchronously activated RGCs produced fewer new branches, but these
      were more stable. The effects of synchronous activation were prevented by the
      inhibition of neurotransmitter release and N-methyl-D-aspartate receptor (NMDAR)
      blockade, which is consistent with a role for synaptic NMDAR activation in the
      stabilization of axonal branches and suppression of further exploratory branch
      addition.

PMID- 24855270
TI  - Stop codon reassignments in the wild.
AB  - The canonical genetic code is assumed to be deeply conserved across all domains
      of life with very few exceptions. By scanning 5.6 trillion base pairs of
      metagenomic data for stop codon reassignment events, we detected recoding in a
      substantial fraction of the >1700 environmental samples examined. We observed
      extensive opal and amber stop codon reassignments in bacteriophages and of opal
      in bacteria. Our data indicate that bacteriophages can infect hosts with a
      different genetic code and demonstrate phage-host antagonism based on code
      differences. The abundance and diversity of genetic codes present in
      environmental organisms should be considered in the design of engineered
      organisms with altered genetic codes in order to preclude the exchange of genetic
      information with naturally occurring species. 

PMID- 24855272
TI  - A science career story.

PMID- 24855271
TI  - Recurrent somatic mutations underlie corticotropin-independent Cushing's
      syndrome.
AB  - Cushing's syndrome is caused by excess cortisol production from the
      adrenocortical gland. In corticotropin-independent Cushing's syndrome, the excess
      cortisol production is primarily attributed to an adrenocortical adenoma, in
      which the underlying molecular pathogenesis has been poorly understood. We report
      a hotspot mutation (L206R) in PRKACA, which encodes the catalytic subunit of
      cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA), in more
      than 50% of cases with adrenocortical adenomas associated with corticotropin
      independent Cushing's syndrome. The L206R PRKACA mutant abolished its binding to
      the regulatory subunit of PKA (PRKAR1A) that inhibits catalytic activity of
      PRKACA, leading to constitutive, cAMP-independent PKA activation. These results
      highlight the major role of cAMP-independent activation of cAMP/PKA signaling by
      somatic mutations in corticotropin-independent Cushing's syndrome, providing
      insights into the diagnosis and therapeutics of this syndrome. 

PMID- 24855275
TI  - A defined, controlled culture system for primary bovine chromaffin progenitors
      reveals novel biomarkers and modulators.
AB  - We present a method to efficiently culture primary chromaffin progenitors from
      the adult bovine adrenal medulla in a defined, serum-free monolayer system.
      Tissue is dissociated and plated for expansion under support by the mitogen basic
      fibroblast growth factor (bFGF). The cultures, although not homogenous, contain a
      subpopulation of cells expressing the neural stem cell marker Hes3 that also
      propagate. In addition, Hes3 is also expressed in the adult adrenal medulla from
      where the tissue is taken. Differentiation is induced by bFGF withdrawal and
      switching to Neurobasal medium containing B27. Following differentiation, Hes3
      expression is lost, and cells acquire morphologies and biomarker expression
      patterns of chromaffin cells and dopaminergic neurons. We tested the effect of
      different treatments that we previously showed regulate Hes3 expression and cell
      number in cultures of fetal and adult rodent neural stem cells. Treatment of the
      cultures with a combination of Delta4, Angiopoietin2, and a Janus kinase
      inhibitor increases cell number during the expansion phase without significantly
      affecting catecholamine content levels. Treatment with cholera toxin does not
      significantly affect cell number but reduces the ratio of epinephrine to
      norepinephrine content and increases the dopamine content relative to total
      catecholamines. These data suggest that this defined culture system can be used
      for target identification in drug discovery programs and that the transcription
      factor Hes3 may serve as a new biomarker of putative adrenomedullary chromaffin
      progenitor cells. 

PMID- 24855278
TI  - Registering diagnostic and prognostic trials of tests: is it the right thing to
      do?

PMID- 24855276
TI  - RepSox slows decay of CD34+ acute myeloid leukemia cells and decreases T cell
      immunoglobulin mucin-3 expression.
AB  - Despite initial response to therapy, most acute myeloid leukemia (AML) patients
      relapse. To eliminate relapse-causing leukemic stem/progenitor cells (LPCs),
      patient-specific immune therapies may be required. In vitro cellular engineering
      may require increasing the "stemness" or immunogenicity of tumor cells and
      activating or restoring cancer-impaired immune-effector and antigen-presenting
      cells. Leukapheresis samples provide the cells needed to engineer therapies: LPCs
      to be targeted, normal hematopoietic stem cells to be spared, and cancer-impaired
      immune cells to be repaired and activated. This study sought to advance
      development of LPC-targeted therapies by exploring nongenetic ways to slow the
      decay and to increase the immunogenicity of primary CD34(+) AML cells. CD34(+)
      AML cells generally displayed more colony-forming and aldehyde dehydrogenase
      activity than CD34(-) AML cells. Along with exposure to bone marrow stromal cells
      and low (1%-5%) oxygen, culture with RepSox (a reprogramming tool and inhibitor
      of transforming growth factor-beta receptor 1) consistently slowed decline of
      CD34(+) AML and myelodysplastic syndrome (MDS) cells. RepSox-treated AML cells
      displayed higher CD34, CXCL12, and MYC mRNA levels than dimethyl sulfoxide
      treated controls. RepSox also accelerated loss of T cell immunoglobulin mucin-3
      (Tim-3), an immune checkpoint receptor that impairs antitumor immunity, from the
      surface of AML and MDS cells. Our results suggest RepSox may reduce Tim-3
      expression by inhibiting transforming growth factor-beta signaling and slow decay
      of CD34(+) AML cells by increasing CXCL12 and MYC, two factors that inhibit AML
      cell differentiation. By prolonging survival of CD34(+) AML cells and reducing
      Tim-3, RepSox may promote in vitro immune cell activation and advance development
      of LPC-targeted therapies. 

PMID- 24855277
TI  - Directed differentiation of human induced pluripotent stem cells toward bone and
      cartilage: in vitro versus in vivo assays.
AB  - The ability to differentiate induced pluripotent stem cells (iPSCs) into
      committed skeletal progenitors could allow for an unlimited autologous supply of
      such cells for therapeutic uses; therefore, we attempted to create novel bone
      forming cells from human iPSCs using lines from two distinct tissue sources and
      methods of differentiation that we previously devised for osteogenic
      differentiation of human embryonic stem cells, and as suggested by other
      publications. The resulting cells were assayed using in vitro methods, and the
      results were compared with those obtained from in vivo transplantation assays.
      Our results show that true bone was formed in vivo by derivatives of several iPSC
      lines, but that the successful cell lines and differentiation methodologies were
      not predicted by the results of the in vitro assays. In addition, bone was formed
      equally well from iPSCs originating from skin or bone marrow stromal cells (also
      known as bone marrow-derived mesenchymal stem cells), suggesting that the iPSCs
      did not retain a "memory" of their previous life. Furthermore, one of the iPSC
      derived cell lines formed verifiable cartilage in vivo, which likewise was not
      predicted by in vitro assays. 

PMID- 24855279
TI  - Repair of congenital heart defects associated with single pulmonary artery.
AB  - BACKGROUND: Experience with complete repair of congenital heart defects
      associated with unilateral absence of a pulmonary artery is limited. The aim of
      this retrospective study was to present our surgical experience of this complex
      category of patients, to analyze immediate results of surgical interventions, and
      to suggest a rational surgical strategy. METHODS: Of 37 patients with a single
      pulmonary artery who underwent complete repair of associated heart defects, the
      left or right pulmonary artery was absent in 32 and 5, respectively. The most
      frequent heart defects were tetralogy of Fallot (n = 25) and ventricular septal
      defect (n = 8). The median age of these patients was 7.1 years. Preoperative
      examinations included echocardiography, cardiac catheterization and
      angiocardiography, with quantitative assessment of the single pulmonary artery.
      In-hospital parameters of surgical outcome were analyzed. RESULTS: Recorded
      hospital mortality was 2.7% (1/37). The single death was in a patient with
      tetralogy of Fallot, agenesis of the left pulmonary artery, and a small diameter
      of the contralateral pulmonary artery (Nakata index 174 mm(2).m(-2)). The right
      to-left ventricular systolic pressure ratio after complete tetralogy of Fallot
      repair in patients who survived the operation was 0.58 +/- 0.11. CONCLUSIONS:
      Complete repair of congenital heart defects in patients with unilateral absence
      of a pulmonary artery is associated with a relatively low risk. If the hilar
      artery is of adequate size, surgical intervention should attempt restoration of
      the communication between the disconnected hilar artery and the pulmonary trunk,
      in addition to repairing the heart defects.

PMID- 24855280
TI  - Cancer risk after cyclophosphamide treatment in idiopathic membranous
      nephropathy.
AB  - BACKGROUND AND OBJECTIVES: Cyclophosphamide treatment improves renal survival in
      patients with idiopathic membranous nephropathy. However, use of cyclophosphamide
      is associated with cancer. The incidence of malignancies in patients with
      idiopathic membranous nephropathy was evaluated, and the cancer risk associated
      with cyclophosphamide use was estimated. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: Patients who attended the clinic were included prospectively from
      1995 on. A crude incidence ratio for the occurrence of malignancy was calculated.
      Incidence ratios were subsequently standardized to potential confounders. Latency
      between cyclophosphamide therapy and the occurrence of cancer was estimated by
      stratifying for time since the start of treatment. Finally, Poisson regression
      was used to obtain a multiple adjusted incidence ratio and investigate the dose
      response relationship between cyclophosphamide and cancer. RESULTS: Data were
      available for 272 patients; the mean age was 51 years, and 70% of the patients
      were men. Median follow-up was 6.0 years (interquartile range=3.6-9.5), and 127
      patients were treated with cyclophosphamide. Cancer incidence was 21.2 per 1000
      person-years in treated patients compared with 4.6 per 1000 person-years in
      patients who did not receive cyclophosphamide, resulting in crude and adjusted
      incidence ratios of 4.6 (95% confidence interval, 1.5 to 18.8) and 3.2 (95%
      confidence interval, 1.0 to 9.5), respectively. CONCLUSION: Cyclophosphamide
      therapy in idiopathic membranous nephropathy gives a threefold increase in cancer
      risk. For the average patient, this finding translates into an increase in annual
      risk from approximately 0.3% to 1.0%. The increased risk of malignancy must be
      balanced against the improved renal survival.

PMID- 24855281
TI  - Balancing cancer risk and efficacy of using cyclophosphamide to treat idiopathic
      membranous nephropathy.

PMID- 24855284
TI  - Involvement of the microvasculature in the pathogenesis of terlipressin-related
      myocardial infarction.
AB  - We report an autopsy case of a 24-year-old man with diagnoses of advanced
      alcoholic liver cirrhosis, portal hypertension, and esophageal variceal bleeding
      that presented extensive myocardial infarction after treatment with terlipressin.
      On postmortem examination the cut surface of the heart presented myocardial
      infarction implicating the left ventricle free wall, apex of the heart and
      ventricular septum. Light microscopic examination revealed that the extensive
      area of cardiac infarction was the result of the sum of diffuse foci of
      microinfarction of various ages interspersed with small clusters of preserved
      myocytes. Moreover, the epicardial vessels were patent while the small
      intramyocardial vessels presented thickened wall, apparent reduction in lumen
      diameter and disruption of endothelial cells indicative of spasm. The
      observations in this case allow clear insight into the involvement of the
      microcirculation in the pathogenesis of myocardial infarction with the use of
      terlipressin.

PMID- 24855282
TI  - Developing risk prediction models for kidney injury and assessing incremental
      value for novel biomarkers.
AB  - The field of nephrology is actively involved in developing biomarkers and
      improving models for predicting patients' risks of AKI and CKD and their
      outcomes. However, some important aspects of evaluating biomarkers and risk
      models are not widely appreciated, and statistical methods are still evolving.
      This review describes some of the most important statistical concepts for this
      area of research and identifies common pitfalls. Particular attention is paid to
      metrics proposed within the last 5 years for quantifying the incremental
      predictive value of a new biomarker. 

PMID- 24855285
TI  - Stent thrombosis in a patient with high on-treatment platelet reactivity despite
      ticagrelor treatment.
AB  - We describe, to the best of our knowledge, the first incidence of stent
      thrombosis in a patient treated with ticagrelor, who exhibited high on-treatment
      platelet reactivity (HTPR) according to platelet reactivity testing. He was on
      clopidrogel and tested for platelet reactivity using the VerifyNow P2Y12 assay.
      The test showed a PRU of 249 and only 12% platelet inhibition. The patient was
      then switched to ticagrelor, with a loading dose of 180 mg given. The patient had
      stent thrombosis three weeks later with an acute myocardial infarction (MI). The
      patient had good platelet inhibition when started on Ticagrelor treatment
      (PRU=33), but had HTPR when the stent thrombosis occurred three weeks later
      (PRU=339). 

PMID- 24855286
TI  - Effects of moderate-to-severe obstructive sleep apnea on the clinical
      manifestations of plaque vulnerability and the progression of coronary
      atherosclerosis in patients with acute coronary syndrome.
AB  - AIMS: It is unclear whether obstructive sleep apnea (OSA) increases the
      recurrence of acute coronary syndrome (ACS) in patients with acute myocardial
      infarction (MI). We hypothesized that moderate-to-severe OSA increased the number
      of adverse cardiovascular events in patients who underwent primary percutaneous
      coronary intervention (PCI). METHODS AND RESULTS: This study included 272
      patients with acute MI. Polysomnography at first admission determined that 124
      patients suffered from moderate-to-severe OSA. The main study outcome measures
      were cardiac death, recurrence of ACS, and re-admission for heart failure. Major
      adverse cardiac events (MACEs) were defined as composite end points of individual
      clinical outcomes. Follow-up coronary angiograms were obtained in 222 patients.
      PCI-related measures were target vessel revascularization and newly necessitated
      PCI for progressive lesions. The moderate-to-severe OSA patients had increased
      ACS recurrence and MACEs compared with patients with mild OSA or without sleep
      apnea (16% vs. 7%, p = 0.014; 22% vs. 11%, p = 0.014, respectively). PCI for
      progressive lesions was also higher in the moderate-to-severe OSA patients (28%
      vs. 15%, p = 0.015). Cox regression analysis showed that moderate-to-severe OSA
      was an independent predictor of ACS recurrence (hazard ratio = 2.30, p = 0.040).
      In addition, moderate-to-severe OSA was an independent predictor of PCI for
      progressive lesions, with a hazard ratio of 2.38 (p = 0.015). CONCLUSIONS:
      Moderate-to-severe OSA increased the risk of ACS and the incidence of PCI for
      progressive lesions. Increased plaque vulnerability might be related to these
      clinical manifestations.

PMID- 24855283
TI  - Distal convoluted tubule.
AB  - The distal convoluted tubule is the nephron segment that lies immediately
      downstream of the macula densa. Although short in length, the distal convoluted
      tubule plays a critical role in sodium, potassium, and divalent cation
      homeostasis. Recent genetic and physiologic studies have greatly expanded our
      understanding of how the distal convoluted tubule regulates these processes at
      the molecular level. This article provides an update on the distal convoluted
      tubule, highlighting concepts and pathophysiology relevant to clinical practice. 

PMID- 24855287
TI  - Training European public health professionals-the role of young professional
      networks.

PMID- 24855288
TI  - The effect of multiple reminders on response patterns in a Danish health survey.
AB  - BACKGROUND: Reminders are routinely applied in surveys to increase response rates
      and reduce the possibility of bias. This study examines the effect of multiple
      reminders on the response rate, non-response bias, prevalence estimates and
      exposure-outcome relations in a national self-administered health survey.
      METHODS: Data derive from the Danish National Health Survey 2010, in which
      298,550 individuals (16 years of age or older) were invited to participate in a
      cross-sectional survey using a mixed-mode approach (paper and web
      questionnaires). At least two reminders were sent to non-respondents, and 177,639
      individuals completed the questionnaire (59.5%). Response patterns were compared
      between four groups of individuals (first mailing respondents, second mailing
      respondents, third mailing respondents and non-respondents). RESULTS: Multiple
      reminders led to an increase in response rate from 36.7 to 59.5%; however, the
      inclusion of second and third mailing respondents did not change the overall
      characteristics of respondents compared with non-respondents. Furthermore, only
      small changes in prevalence estimates and exposure-outcome relationships were
      observed when including second and third mailing respondents compared with only
      first mailing respondents. CONCLUSIONS: Multiple reminders were an effective way
      to increase the response rate in a national Danish health survey. However, when
      differences do exist between respondents and non-respondents, the results suggest
      that second and third mailings are unlikely to eliminate these differences.
      Overall, multiple reminders seemed to have only minor effect on response patterns
      and study conclusions in the present study.

PMID- 24855289
TI  - Diffusion weighted imaging of nasopharyngeal adenoid hypertrophy.
AB  - BACKGROUND: Diffusion-weighted imaging (DWI) could be helpful for the
      differentiation of malignant and benign entities. Nasopharyngeal adenoid
      hypertrophy (NAH) is a typical benign lesion. DWI appearances of this lesion have
      not been reported previously. PURPOSE: To identify and to analyse DWI findings of
      NAH. MATERIAL AND METHODS: We analyzed 688 MR investigations of the head
      performed at our institution. Magnetic resonance imaging (MRI) was obtained at a
      1.5 T MRI device. Beside normal standard sequences DWI was obtained using a
      multislice single-shot echo-planar sequence. DWI was performed with b values of
      0, 500, and 1000 s/mm(2). RESULTS: The mean whole lesion ADC value was 0.83 +/-
      0.12 * 10(-3) mm(2) s(-1) (median, 0.82 * 10(-3) mm(2) s(-1); range, 0.58-1.45 *
      10(-3) mm(2) s(-1)). The mean ADC value of solid areas of NAH was 0.59 +/- 0.11 *
      10(-3) mm(2) s(-1) (range, 0.36-0.84 * 10(-3) mm(2) s(-1)). CONCLUSION: Although
      NAH is a benign lesion, it shows low ADC values both in childhood and in adults.
      This finding should be kept in mind to avoid possible misinterpretations as a
      malignant lesion.

PMID- 24855290
TI  - Submilisievert ultralow-dose CT colonography using iterative reconstruction
      technique: a feasibility study.
AB  - BACKGROUND: Computed tomography (CT) colonography is a well established modality
      for the examination of symptomatic patients as well as in screening. Recent
      technical advances in improving image quality by iterative reconstruction
      contribute to the reduction of the radiation dose which is a major concern in CT
      imaging. PURPOSE: To evaluate image quality of ultralow-dose submilisievert CT
      colonography using hybrid iterative reconstruction technique. MATERIAL AND
      METHODS: Sixteen patients underwent contrast-enhanced CT colonography with
      standard protocol in supine position and ultralow-dose protocol in prone
      position. Ultralow-dose datasets were reconstructed with filtered back projection
      and an advanced hybrid iterative reconstruction technique. Two radiologists
      independently evaluated 96 colonic segments for image quality in the endoluminal
      view and axial thin sections. Colonic distension, smoothness of colonic wall and
      distortion of folds in the endoluminal view, sharpness of colonic wall
      delineation, perceived image noise, and presence of photon starvation artifact
      were rated on a five-point scale. Intraluminal noise expressed as standard
      deviation of Hounsfield density was measured in all segments. RESULTS: The mean
      radiation dose was 0.42 mSv and 5.48 mSv in prone and supine scans, respectively.
      All distended segments were rated evaluable in standard dose and ultralow-dose
      series reconstructed with the iterative reconstruction technique, whereas in 61%
      segments image quality was rated poor or unacceptable in ultralow-dose series
      where filtered back projection was used with worst ratings in the rectum and the
      sigmoid colon. CONCLUSION: This pilot study shows that iterative reconstruction
      technique is a feasible method to decrease the radiation dose from CT
      colonography for both positions below 1mSv. Further investigations of larger
      scale need to be done to clarify, whether such a low radiation dose would
      influence the detection of polyps.

PMID- 24855292
TI  - Complete Genome Sequence of Ureaplasma parvum Serovar 3 Strain SV3F4, Isolated in
      Japan.
AB  - Here, we present the complete genome sequence of Ureaplasma parvum serovar 3,
      clinical strain SV3F4, isolated from a Japanese patient with a history of an
      infectious abortion. 

PMID- 24855291
TI  - Genome Analysis of Pseudomonas aeruginosa Bacteriophage KPP23, Belonging to the
      Family Siphoviridae.
AB  - Bacteriophage (phage) therapy is expected to become an alternative therapy for
      Pseudomonas aeruginosa infections. P. aeruginosa phage KPP23 is a newly isolated
      phage belonging to the family Siphoviridae and may be a therapeutic phage
      candidate. We report its complete genome, which comprises 62,774 bp of double
      stranded DNA containing 95 open reading frames. 

PMID- 24855293
TI  - Draft Genome Sequence of Burkholderia sp. Strain MP-1, a Methyl Parathion (MP)
      Degrading Bacterium from MP-Contaminated Soil.
AB  - Burkholderia sp. strain MP-1 was isolated from pesticide-contaminated soil.
      Herein, we report the draft genome sequence of strain MP-1, which contains 168
      contigs of 8,611,053 bp, with a G+C content of 62.55% and 7,631 protein-coding
      genes. 

PMID- 24855294
TI  - Draft Genome Sequences of Two Isolates of the Roseobacter Group, Sulfitobacter
      sp. Strains 3SOLIMAR09 and 1FIGIMAR09, from Harbors of Mallorca Island
      (Mediterranean Sea).
AB  - We present the draft genome sequences of two isolates of the Roseobacter lineage,
      3SOLIMAR09 and 1FIGIMAR09, which were obtained from harbors of Mallorca Island,
      Spain, and are affiliated with the Sulfitobacter genus. Both isolates harbor the
      complete gene set for protocatechuate catabolism and incomplete pathways for
      several additional monoaromatic compounds. 

PMID- 24855295
TI  - Draft Genome Sequence of Bacillus thuringiensis NBIN-866 with High Nematocidal
      Activity.
AB  - Bacillus thuringiensis NBIN-866, a Gram-positive bacterium, was isolated from
      soil in China. We announce here the draft genome sequence of strain B.
      thuringiensis NBIN-866, which possesses highly nematocidal factors, such as
      proteins and small molecular peptides. 

PMID- 24855297
TI  - Complete genome sequences of three novel human papillomavirus types, 175, 178,
      and 180.
AB  - We report the characterization of three novel human papillomavirus (HPV) types of
      the genus Gammapapillomavirus. HPV175 and HPV180 were isolated from a condyloma.
      HPV178 was isolated from healthy skin adjacent to an actinic keratosis. 

PMID- 24855296
TI  - Draft Genome Sequences of Marinobacter similis A3d10T and Marinobacter salarius
      R9SW1T.
AB  - Here, we present the draft genomes of Marinobacter similis A3d10(T), a potential
      plastic biodegrader, and Marinobacter salarius R9SW1(T), isolated from
      radioactive waters. This genomic information will contribute information on the
      genetic basis of the metabolic pathways for the degradation of both plastic and
      radionuclides. 

PMID- 24855298
TI  - Draft Genome Sequence of the Nonstarter Bacteriocin-Producing Strain Enterococcus
      mundtii CRL35.
AB  - Enterococcus mundtii CRL35 is a bacteriocinogenic strain isolated from an
      artisanal cheese of northwestern Argentina. Here we report its draft genome
      sequence, consisting of 82 contigs. In silico genomic analysis of
      biotechnological properties was performed to determine the potential of this
      microorganism to be used in a food model system. 

PMID- 24855299
TI  - Genome Sequence of the Pathogenic Fungus Sporothrix schenckii (ATCC 58251).
AB  - Sporothrix schenckii is a pathogenic dimorphic fungus that grows as a yeast and
      as mycelia. This species is the causative agent of sporotrichosis, typically a
      skin infection. We report the genome sequence of S. schenckii, which will
      facilitate the study of this fungus and of the Sporothrix schenckii group. 

PMID- 24855300
TI  - Complete Genome Sequence of the Highly Virulent Aeromonas hydrophila AL09-71
      Isolated from Diseased Channel Catfish in West Alabama.
AB  - Aeromonas hydrophila AL09-71 was isolated from diseased channel catfish in west
      Alabama during a 2009 disease outbreak. The full genome of A. hydrophila AL09-71
      is 5,023,861 bp. The availability of this genome will allow comparative genomics
      to identify genes involved in pathogenesis or immunogens for the purpose of
      vaccine development. 

PMID- 24855301
TI  - Draft Genome Sequence of Endocarpon pusillum Strain KoLRILF000583.
AB  - Lichen Endocarpon pusillum is a highly desiccation-tolerant and dominant species
      in biological soil crusts in arid and semi-arid regions. We report the draft
      genome sequence of a lichen-forming fungus, E. pusillum strain KoLRILF000583. The
      draft genome assembly has a size of 37,173,200 bp with a GC content of 49.71%,
      consisting of 40 scaffolds. 

PMID- 24855302
TI  - Draft Genome Sequence of Streptococcus parauberis Strain SK-417, Isolated from
      Diseased Sebastes ventricosus in Kagoshima, Japan.
AB  - Streptococcus parauberis strain SK-417 was isolated from the brain of a diseased
      Sebastes ventricosus, collected from an aquaculture farm in April 2013 in
      Kagoshima Prefecture, Japan. The draft genome sequence, obtained with a 454 GS
      Junior sequencing system, consists of 33 large contigs of >500 bp, totaling
      1,958,836 bp, and has a G+C content of 35.4%. 

PMID- 24855303
TI  - Complete genome sequence of a human enterovirus 71 strain isolated from a fatal
      case in shanghai, china, in 2012.
AB  - The complete genome sequence of a human enterovirus 71 strain (SH12-276),
      isolated from a fatal case in Shanghai in 2012, was determined. Phylogenetic
      analysis based on the complete genome sequence classified this strain into
      subgenotype C4. 

PMID- 24855304
TI  - Draft Genome Sequence of Potassium-Dependent Alkaliphilic Bacillus sp. Strain TS
      2, Isolated from a Jumping Spider.
AB  - The potassium-dependent alkaliphilic Bacillus sp. strain TS-2 was isolated from
      the mashed extract of a jumping spider, and its draft genome sequence was
      obtained. Comparative genomic analysis with a previously sequenced sodium
      dependent alkaliphilic Bacillus species may reveal potassium-dependent alkaline
      adaptation mechanisms. 

PMID- 24855305
TI  - Draft Genome Sequence of Lactobacillus plantarum wikim18, Isolated from Korean
      Kimchi.
AB  - This report describes the draft genome sequence of Lactobacillus plantarum strain
      wikim18, isolated from the traditional Korean food kimchi. The reads generated by
      Ion Torrent PGM were assembled into 327 contigs. RAST annotation of the genome
      revealed 12 tRNAs and 3,316 protein-coding gene sequences. 

PMID- 24855306
TI  - Draft Genome Sequence of Cupriavidus sp. Strain SK-4, a di-ortho-Substituted
      Biphenyl-Utilizing Bacterium Isolated from Polychlorinated Biphenyl-Contaminated
      Sludge.
AB  - Cupriavidus sp. strain SK-4 is a bacterium capable of growing aerobically on
      monochlorobiphenyls and dichlorobiphenyls as the sole carbon sources for growth.
      Here, we report its draft genome sequence with the aim of facilitating an
      understanding of polychlorinated biphenyl biodegradation mechanisms. 

PMID- 24855307
TI  - Draft Genome Sequence of Multidrug-Resistant Mycobacterium tuberculosis Strain
      CWCFVRF MDRTB 670, Isolated from the Sputum of a Patient from Chennai, India,
      with Clinically Suspected Tuberculosis.
AB  - We announce the draft genome sequence of a multidrug-resistant Mycobacterium
      tuberculosis strain (CWCFVRF MDRTB 670) isolated from sputum from a patient with
      clinically suspected tuberculosis. 

PMID- 24855308
TI  - Complete Genome Sequences of Two Escherichia coli O145:H28 Outbreak Strains of
      Food Origin.
AB  - Escherichia coli O145:H28 strain RM12581 was isolated from bagged romaine lettuce
      during a 2010 U.S. lettuce-associated outbreak. E. coli O145:H28 strain RM12761
      was isolated from ice cream during a 2007 ice cream-associated outbreak in
      Belgium. Here we report the complete genome sequences and annotation of both
      strains. 

PMID- 24855309
TI  - Draft Genome Sequence of Actibacterium mucosum KCTC 23349, a Marine
      Alphaproteobacterium with Complex Ionic Requirements Isolated from Mediterranean
      Seawater at Malvarrosa Beach, Valencia, Spain.
AB  - Strain R46 (CECT 7668; KCTC 23349), a nomenclatural type of Actibacterium
      mucosum, was isolated from surface seawater collected at Malvarrosa Beach
      (Valencia, Spain) in July 2008. The draft genome sequence of strain R46
      (approximately 3.72 Mbp) contains 22 scaffolds and 3,619 protein-encoding genes,
      with a G+C content of 60.8 mol%. 

PMID- 24855310
TI  - Draft Genome Sequence of Frankia sp. Strain Thr, a Nitrogen-Fixing
      Actinobacterium Isolated from the Root Nodules of Casuarina cunninghamiana Grown
      in Egypt.
AB  - Nitrogen-fixing actinobacteria of the genus Frankia are symbionts of woody
      dicotyledonous plants termed actinorhizal plants. We report here a 5.3-Mbp draft
      genome sequence for Frankia sp. stain Thr, a nitrogen-fixing actinobacterium
      isolated from root nodules of Casuarina cunninghamiana collected in Egypt. 

PMID- 24855311
TI  - Draft Genome Sequence of Pantoea ananatis Strain LMG 2665T, a Bacterial Pathogen
      of Pineapple Fruitlets.
AB  - We report the draft genome sequence of Pantoea ananatis LMG 2665(T), the
      bacterial causal agent of pineapple fruitlet rot. 

PMID- 24855312
TI  - Isolated non-hemorrhagic cecal varices.
AB  - Ectopic varices (those outside of the gastro-esophageal region) are occasionally
      found on endoscopy in patients with portal hypertension; however they account for
      a small minority of all variceal bleeds. Cases of isolated cecal varices are
      quite rare and, when described, often present with acute hemorrhage or evidence
      of occult bleeding. We present the case of a 29-year-old male with a history of
      idiopathic portal vein thrombosis and known esophageal varices, who presented for
      evaluation of abdominal pain. Cecal varices were found on endoscopy, without
      evidence of bleeding and without varices in the remainder of the colon or rectum.
      Endoscopic ultrasound and computed tomography were useful in confirming the
      diagnosis and natural history of these unusual varices. 

PMID- 24855313
TI  - The Effectiveness of a Culturally Sensitive Cognitive Behavioral Group
      Intervention for Latino Alzheimer's Caregivers.
AB  - PURPOSE OF THE STUDY: Demographic projections suggest that the older Latino
      population will experience the fastest growth among all racial/ethnic groups; and
      by 2050 will constitute 20% of the nation's seniors. Yet, Latino Alzheimer's
      elders and their families remain underrepresented in the health care system and
      caregiver intervention studies. To address this gap, this study tested the
      effectiveness of Circulo de Cuidado, a culturally-sensitive, cognitive behavioral
      (CBT) group intervention, in supporting Latino families' ability to manage the
      disease's neuropsychiatric symptoms and improve caregiver well-being. DESIGN AND
      METHODS: Using a randomized controlled trial design, 67 caregivers were assigned
      to the CBT experimental condition or the psychoeducational (PED) control
      condition and interviewed at baseline, post-group, and 3 months follow-up. The 2
      manualized interventions had the same structure: 5 weekly 90-minute group
      sessions, followed by telephone coaching at 3, 6, 9 and 12 weeks post-group.
      RESULTS: Repeated measures analysis of covariance revealed significant group by
      time interaction effects. Compared with the PED participants, CBT participants
      reported lower neuropsychiatric symptoms in their relative, less caregiver
      distress about neuropsychiatric symptoms, a greater sense of caregiver self
      efficacy, and less depressive symptoms over time. IMPLICATIONS: Our findings
      offer preliminary evidence that a culturally tailored, CBT group intervention
      targeted toward neuropsychiatric symptom management has positive psychological
      benefits for Latino caregivers.

PMID- 24855314
TI  - Aging in the Czech Republic.
AB  - The goal was to provide an overview of main issues relevant to aging in the Czech
      Republic. The Czech Republic is a former Eastern Bloc nation of about 10.5
      million. Older adults are overrepresented relative to those under age 15. Life
      expectancy currently hovers around 78 years (75 for men/81 for women), a number
      slightly higher than most of Eastern Europe but lower than most of Western
      Europe. Cardiovascular diseases account for about 50% of all mortality, which is
      one of the highest rates in Europe and therefore of particular concern. Lifestyle
      habits, especially high alcohol consumption, a high rate of smokers, and high-fat
      diet relative to most other European countries and the United States, combined
      with relatively low expenditures for health promotion, appear important in the
      context of high cardiovascular mortality. Long-term care is funded mostly by
      state and local governments. The country has tried to address issues associated
      with insufficient capacity and low quality in long-term care, a particularly
      prominent problem in the Czech Republic compared with other European countries.
      The recently established International Clinical Research Center brings new
      possibilities for collaborative research in the Czech Republic, including
      research specific to aging. Improving long-term care and establishing
      methodologically sound longitudinal data sets are among the most pressing issues,
      although sustaining the pension system strained by increasing life expectancy,
      low retirement age, and extensive government-sponsored benefits has also recently
      emerged as a critical issue. 

PMID- 24855315
TI  - A roadmap for functional structural variants in the soybean genome.
AB  - Gene structural variation (SV) has recently emerged as a key genetic mechanism
      underlying several important phenotypic traits in crop species. We screened a
      panel of 41 soybean (Glycine max) accessions serving as parents in a soybean
      nested association mapping population for deletions and duplications in more than
      53,000 gene models. Array hybridization and whole genome resequencing methods
      were used as complementary technologies to identify SV in 1528 genes, or
      approximately 2.8%, of the soybean gene models. Although SV occurs throughout the
      genome, SV enrichment was noted in families of biotic defense response genes.
      Among accessions, SV was nearly eightfold less frequent for gene models that have
      retained paralogs since the last whole genome duplication event, compared with
      genes that have not retained paralogs. Increases in gene copy number, similar to
      that described at the Rhg1 resistance locus, account for approximately one-fourth
      of the genic SV events. This assessment of soybean SV occurrence presents a
      target list of genes potentially responsible for rapidly evolving and/or adaptive
      traits. 

PMID- 24855319
TI  - Transition in congenital heart disease: it takes a village.

PMID- 24855318
TI  - An unusual cause of a non-ST segment elevation myocardial infarction: answer.

PMID- 24855316
TI  - Genetic control of maize shoot apical meristem architecture.
AB  - The shoot apical meristem contains a pool of undifferentiated stem cells and
      generates all above-ground organs of the plant. During vegetative growth, cells
      differentiate from the meristem to initiate leaves while the pool of meristematic
      cells is preserved; this balance is determined in part by genetic regulatory
      mechanisms. To assess vegetative meristem growth and genetic control in Zea mays,
      we investigated its morphology at multiple time points and identified three
      stages of growth. We measured meristem height, width, plastochron internode
      length, and associated traits from 86 individuals of the intermated B73 * Mo17
      recombinant inbred line population. For meristem height-related traits, the
      parents exhibited markedly different phenotypes, with B73 being very tall, Mo17
      short, and the population distributed between. In the outer cell layer,
      differences appeared to be related to number of cells rather than cell size. In
      contrast, B73 and Mo17 were similar in meristem width traits and plastochron
      internode length, with transgressive segregation in the population. Multiple loci
      (6-9 for each trait) were mapped, indicating meristem architecture is controlled
      by many regions; none of these coincided with previously described mutants
      impacting meristem development. Major loci for height and width explaining 16%
      and 19% of the variation were identified on chromosomes 5 and 8, respectively.
      Significant loci for related traits frequently coincided, whereas those for
      unrelated traits did not overlap. With the use of three near-isogenic lines, a
      locus explaining 16% of the parental variation in meristem height was validated.
      Published expression data were leveraged to identify candidate genes in
      significant regions. 

PMID- 24855320
TI  - Diagnosis and treatment of pulmonary hypertension.

PMID- 24855317
TI  - Species-level deconvolution of metagenome assemblies with Hi-C-based contact
      probability maps.
AB  - Microbial communities consist of mixed populations of organisms, including
      unknown species in unknown abundances. These communities are often studied
      through metagenomic shotgun sequencing, but standard library construction methods
      remove long-range contiguity information; thus, shotgun sequencing and de novo
      assembly of a metagenome typically yield a collection of contigs that cannot
      readily be grouped by species. Methods for generating chromatin-level contact
      probability maps, e.g., as generated by the Hi-C method, provide a signal of
      contiguity that is completely intracellular and contains both intrachromosomal
      and interchromosomal information. Here, we demonstrate how this signal can be
      exploited to reconstruct the individual genomes of microbial species present
      within a mixed sample. We apply this approach to two synthetic metagenome
      samples, successfully clustering the genome content of fungal, bacterial, and
      archaeal species with more than 99% agreement with published reference genomes.
      We also show that the Hi-C signal can secondarily be used to create scaffolded
      genome assemblies of individual eukaryotic species present within the microbial
      community, with higher levels of contiguity than some of the species' published
      reference genomes. 

PMID- 24855321
TI  - The Genomic Revolution and Beliefs about Essential Racial Differences: A Backdoor
      to Eugenics?
AB  - Could the explosion of genetic research in recent decades affect our conceptions
      of race? In Backdoor to Eugenics, Duster argues that reports of specific racial
      differences in genetic bases of disease, in part because they are presented as
      objective facts whose social implications are not readily apparent, may heighten
      public belief in more pervasive racial differences. We tested this hypothesis
      with a multi-method study. A content analysis showed that news articles
      discussing racial differences in genetic bases of disease increased significantly
      between 1985 and 2008 and were significantly less likely than non-health-related
      articles about race and genetics to discuss social implications. A survey
      experiment conducted with a nationally representative sample of 559 adults found
      that a news-story vignette reporting a specific racial difference in genetic risk
      for heart attacks (the Backdoor Vignette) produced significantly greater belief
      in essential racial differences than did a vignette portraying race as a social
      construction or a no-vignette condition. The Backdoor Vignette produced beliefs
      in essential racial differences that were virtually identical to those produced
      by a vignette portraying race as a genetic reality. These results suggest that an
      unintended consequence of the genomic revolution may be the reinvigoration of age
      old beliefs in essential racial differences.

PMID- 24855322
TI  - Measuring Ethnic Clustering and Exposure with the Q statistic: An Exploratory
      Analysis of Irish, Germans, and Yankees in 1880 Newark.
AB  - The study of population patterns has animated a large body of urban social
      research over the years. An important part of this literature is concerned with
      the identification and measurement of segregation patterns. Recently, emphatic
      calls have been made to develop measures that are better able to capture the
      geography of population patterns. The objective of this paper is to demonstrate
      the application of the Q statistic, developed for the analysis of spatial
      association of qualitative variables, to the detection of ethnic clustering and
      exposure patterns. The application is to historical data from 1880 Newark in the
      United States, with individuals classified by ethnicity and geo-coded by place of
      residence. Three ethnic groups, termed Irish, Germans, and Yankees are
      considered. Exploratory analysis with the Q statistic identifies significant
      differences in the tendency of individuals and building occupancy to cluster by
      ethnicity. In particular, there is evidence of a strong affinity within ethnic
      clusters, and some intermingling between Yankee and Irish residents. In contrast,
      the exposure of Germans to individuals of other groups is found to be more
      limited.

PMID- 24855324
TI  - Response Diversity and Resilience in Social-Ecological Systems.
AB  - Recent work in ecology suggests that the diversity of responses to environmental
      change among species contributing to the same ecosystem function can strongly
      influence ecosystem resilience. To render this important realization more useful
      for understanding coupled human-natural systems, we broaden the concept of
      response diversity to include heterogeneity in human decisions and action. Simply
      put, not all actors respond the same way to challenges, opportunities, and risks.
      The range, prevalence, and spatial and temporal distributions of different
      responses may be crucial to the resilience or the transformation of a social
      ecological system, and thus have a bearing on human vulnerability and well-being
      in the face of environmental, socioeconomic, and political change. Response
      diversity can be seen at multiple scales (e.g., household, village, region) and
      response diversity at one scale may act synergistically with or contrary to the
      effects of diversity at another scale. Although considerable research on the
      sources of response diversity has been done, our argument is that the
      consequences of response diversity warrant closer attention. We illustrate this
      argument with examples drawn from our studies of two East African pastoral
      populations and discuss the relationship of response diversity to characteristics
      of social-ecological systems that can promote or diminish resilience.

PMID- 24855323
TI  - A Stability-Indicating HPLC Method for the Determination of Nitrosylcobalamin (NO
      Cbl), a Novel Vitamin B12 Analog.
AB  - Nitrosylcobalamin (NO-Cbl), a novel vitamin B12 analog and anti-tumor agent,
      functions as a biologic 'Trojan horse', utilizing the vitamin B12 transcobalamin
      II transport protein and cell surface receptor to specifically target cancer
      cells. a stability-indicating HPLC method was developed for the detection of NO
      Cbl during forced degradation studies. This method utilized an ascentis(r) RP
      amide (150 mm * 4.6 mm, 5 MUm) column at 35  degrees C with a mobile phase (1.0
      mL min-1) combining a gradient of methanol and an acetate buffer at pH 6.0.
      Detection wavelengths of 450 and 254 nm were used to detect corrin and non-corrin
      based products, respectively. NO-Cbl, synthesized from hydroxocobalamin and pure
      nitric oxide gas, was subjected to degradative stress conditions including
      oxidation, hydrolysis and thermal and radiant energy challenge. The method was
      validated by assessing linearity, accuracy, precision, detection and quantitation
      limits and robustness. The method was applied successfully for purity assessment
      of synthesized NO-Cbl and for the determination of NO-Cbl during kinetic studies
      in aqueous solution and in solid-state degradation assessments. This HPLC method
      is suitable for the separation of cobalamins in aqueous and methanolic solutions,
      for routine detection of NO-Cbl and for purity assessment of synthesized NO-Cbl.
      additionally, this method has potential application in identification and
      monitoring of diseases involving altered nitric oxide homeostasis where vitamin
      B12 therapy is utilized to scavenge excess nitric oxide, subsequently resulting
      in the in vivo production of NO-Cbl.

PMID- 24855325
TI  - Genetics and the Sociology of Identity.

PMID- 24855326
TI  - Adult Attachment Style and Stress as Risk Factors for Early Maternal Sensitivity
      and Negativity.
AB  - The current study examined the individual and joint effects of self-reported
      adult attachment style, psychological distress, and parenting stress on maternal
      caregiving behaviors at 6 and 12 months of child age. We proposed a diathesis
      stress model to examine the potential deleterious effects of stress for mothers
      with insecure adult attachment styles. Data from 137 mothers were gathered by the
      longitudinal Durham Child Health and Development Study. Mothers provided self
      reports using Hazan and Shaver's (1987) Adult Attachment Style measure, the Brief
      Symptom Inventory, and the Parent Stress Inventory; observations of parenting
      data were made from 10-minute free play interactions. Consistently avoidant
      mothers were less sensitive with their infants than consistently secure mothers;
      however, this effect was limited to avoidant mothers who experienced elevated
      levels of psychological distress. Results suggest that the association between
      insecure adult attachment style and insensitive parenting behavior is moderated
      by concurrent psychosocial stress. Clinical implications for these findings are
      discussed.

PMID- 24855327
TI  - Attributions of Fathering Behaviors Among Adolescents: The Role of Gender,
      Ethnicity, Family Structure, and Depressive Symptoms.
AB  - Little attention has been paid to how early adolescents make attributions for
      their fathers' behavior. Guided by symbolic interaction theory, we examined how
      adolescent gender, ethnicity, family structure, and depressive symptoms explained
      attributions for residential father behavior. 382 adolescents, grouped by
      ethnicity (European American, Mexican American) and family structure (intact,
      stepfamilies), reported attributions for their fathers' positive and negative
      behaviors. Results indicated that for positive events girls made significantly
      more stable attributions, whereas boys made more unstable attributions. Mexican
      American adolescents tended to make more unstable attributions for positive
      events than European Americans, and adolescents from intact families made more
      stable attributions for positive events than adolescents from stepfamilies.
      Implications are discussed for the role of attributions in father-adolescent
      relationships as prime for intervention in families.

PMID- 24855328
TI  - Two-Step Hypothesis Testing When the Number of Variables Exceeds the Sample Size.
AB  - Medical images and genetic assays typically generate data with more variables
      than subjects. Scientists may use a two-step approach for testing hypotheses
      about Gaussian mean vectors. In the first step, principal components analysis
      (PCA) selects a set of sample components fewer in number than the sample size. In
      the second step, applying classical multivariate analysis of variance (MANOVA)
      methods to the reduced set of variables provides the desired hypothesis tests.
      Simulation results presented here indicate that success of the PCA in the first
      step requires nearly all variation to occur in population components far fewer in
      number than the number of subjects. In the second step, multivariate tests fail
      to attain reasonable power except in restrictive, favorable cases. The results
      encourage using other approaches discussed in the article to provide dependable
      hypothesis testing with high dimension, low sample size data (HDLSS).

PMID- 24855329
TI  - Intergenerational Transmission of Emotion Dysregulation Through Parental
      Invalidation of Emotions: Implications for Adolescent Internalizing and
      Externalizing Behaviors.
AB  - We examined parent emotion dysregulation as part of a model of family emotion
      related processes and adolescent psychopathology. Participants were 80 parent
      adolescent dyads (mean age = 13.6; 79 % African-American and 17 % Caucasian) with
      diverse family composition and socioeconomic status. Parent and adolescent dyads
      self-reported on their emotion regulation difficulties and adolescents reported
      on their perceptions of parent invalidation (i.e., punishment and neglect) of
      emotions and their own internalizing and externalizing behaviors. Results showed
      that parents who reported higher levels of emotion dysregulation tended to
      invalidate their adolescent's emotional expressions more often, which in turn
      related to higher levels of adolescent emotion dysregulation. Additionally,
      adolescent-reported emotion dysregulation mediated the relation between parent
      invalidation of emotions and adolescent internalizing and externalizing
      behaviors. Potential applied implications are discussed.

PMID- 24855330
TI  - Perceptions of Parental Awareness of Emotional Responses to Stressful Life
      Events.
AB  - There is a need to better understand family processes related to recovery from
      past stressful life events. The present study aimed to investigate links between
      perceptions of parental awareness regarding stressful life events, continued
      event-related rumination, and current symptoms of depression. Students at a
      diverse, urban university completed a life events checklist and a semi-structured
      interview regarding family processing of stressful life events, as well as self
      report measures of event-related rumination and depression. Results indicated
      that perceptions of mothers' and fathers' awareness of sadness regarding
      stressful life events as well as mothers' and fathers' verbal event processing
      predicted symptoms of event-related rumination and depression. Results support
      the inclusion of perceptions of parental awareness in the understanding of how
      emerging adults continue to cope with past stressful life events.

PMID- 24855331
TI  - Racial/Ethnic Variations in the Consequences of Religious Participation for
      Academic Achievement at Elite Colleges and Universities.
AB  - Research has not investigated how much of the previously documented positive
      association between high school religious service attendance and college grades
      is mediated by campus religious group participation. Nor do we know whether
      campus religious group involvement is an important mediator for black and
      Hispanic students who experience grade-lowering stereotype threat at historically
      white institutions. Path analyses conducted on a racially diverse sample of
      students at 28 elite institutions indicate that religious group involvement in
      college mediates the positive relationship between high school service attendance
      and college grades for Hispanic and to some extent black students. For Asian and
      white students, high school service attendance is positively associated with
      grades net of religious group involvement on campus. Asians frequently attending
      high school services on average earn a grade-point average of 0.12 points above
      Asians who never attended, net of controls.

PMID- 24855332
TI  - Overcoming Barriers to HIV Treatment Adherence: A Brief Cognitive Behavioral
      Intervention for HIV-Positive Adults on Antiretroviral Treatment.
AB  - Maximizing HIV treatment adherence is critical in efforts to optimize health
      outcomes and to prevent further HIV transmission. The Balance Project
      intervention uses cognitive behavioral approaches to improve antiretroviral
      medication adherence through promoting adaptive coping with medication side
      effect and distress related to HIV. This 5-session intervention has been
      documented to prevent nonadherence among persons living with HIV who experience
      high levels of distress associated with their antiretroviral medication side
      effects. We describe the theoretical underpinnings of the intervention, provide
      details of the training and session protocols with a case example, and discuss
      implications for future applications of the intervention in both research and
      clinical settings.

PMID- 24855333
TI  - Assignment of Calibration Information to Deeper Phylogenetic Nodes is More
      Effective in Obtaining Precise and Accurate Divergence Time Estimates.
AB  - Divergence time estimation has become an essential tool for understanding
      macroevolutionary events. Molecular dating aims to obtain reliable inferences,
      which, within a statistical framework, means jointly increasing the accuracy and
      precision of estimates. Bayesian dating methods exhibit the propriety of a linear
      relationship between uncertainty and estimated divergence dates. This
      relationship occurs even if the number of sites approaches infinity and places a
      limit on the maximum precision of node ages. However, how the placement of
      calibration information may affect the precision of divergence time estimates
      remains an open question. In this study, relying on simulated and empirical data,
      we investigated how the location of calibration within a phylogeny affects the
      accuracy and precision of time estimates. We found that calibration priors set at
      median and deep phylogenetic nodes were associated with higher precision values
      compared to analyses involving calibration at the shallowest node. The results
      were independent of the tree symmetry. An empirical mammalian dataset produced
      results that were consistent with those generated by the simulated sequences.
      Assigning time information to the deeper nodes of a tree is crucial to guarantee
      the accuracy and precision of divergence times. This finding highlights the
      importance of the appropriate choice of outgroups in molecular dating. 

PMID- 24855334
TI  - Spectrophotometric and spectrofluorimetric studies on azilsartan medoxomil and
      chlorthalidone to be utilized in their determination in pharmaceuticals.
AB  - The recently approved angiotensin II receptor blocker, azilsartan medoxomil
      (AZL), was determined spectrophotometrically and spectrofluorimetrically in its
      combination with chlorthalidone (CLT) in their combined dosage form. The UV
      spectrophotometric technique depends on simultaneous measurement of the first
      derivative spectra for AZL and CLT at 286 and 257 nm, respectively, in methanol.
      The spectrofluorimetric technique depends on measurement of the fourth derivative
      of the synchronous spectra intensities of AZL in presence of CLT at 298 nm in
      methanol. The effects of different solvents on spectrophotometric and
      spectrofluorimetric responses were studied. For, the spectrofluorimetric study,
      the effect of pH and micelle-assisted fluorescence enhancement were also studied.
      Linearity, accuracy, and precision were found to be satisfactory over the
      concentration ranges of 8-50 MUg mL(-1) and 2-20 MUg mL(-1) for AZL and CLT,
      respectively, in the spectrophotometric method as well as 0.01-0.08 MUg mL(-1)
      for AZL in the spectrofluorimetric method. The methods were successfully applied
      for the determination of the studied drugs in their co-formulated tablets. The
      developed methods are inexpensive and simple for the quality control and routine
      analysis of the cited drugs in bulk and in pharmaceuticals. 

PMID- 24855336
TI  - Prospective unmasked randomized evaluation of the iStent inject ((r)) versus two
      ocular hypotensive agents in patients with primary open-angle glaucoma.
AB  - PURPOSE: The purpose of this study was to compare outcomes of subjects with open
      angle glaucoma (OAG) not controlled on one medication who underwent either
      implantation of two iStent inject ((r)) trabecular micro-bypass devices or
      received medical therapy consisting of a fixed combination of
      latanoprost/timolol. PATIENTS AND METHODS: Of 192 subjects who qualified for the
      study and were enrolled, 94 were randomized to surgery with implantation of two
      iStent inject((r)) devices in the treated eye and 98 to receive medical therapy.
      RESULTS: At the month 12 visit, 94.7% of eyes (89/94) in the stent group reported
      an unmedicated intraocular pressure (IOP) reduction of >=20% versus baseline
      unmedicated IOP, and 91.8% of eyes (88/98) in the medical therapy group reported
      an IOP reduction >=20% versus baseline unmedicated IOP. A 17.5% between-group
      treatment difference in favor of the iStent inject group was statistically
      significant (P=0.02) at the >=50% level of IOP reduction. An IOP <=18 mmHg was
      reported in 92.6% of eyes (87/94) in the iStent inject group and 89.8% of eyes
      (88/98) in the medical therapy group. Mean (standard deviation) IOP decreases
      from screening of 8.1 (2.6) mmHg and 7.3 (2.2) mmHg were reported in the iStent
      inject and medical therapy groups, respectively. A high safety profile was also
      noted in this study in both the iStent inject and medical therapy groups, as
      measured by stable best corrected visual acuity, cup-to-disc ratio, and adverse
      events. CONCLUSION: These data show that the use of iStent inject is at least as
      effective as two medications, with the clinical benefit of reducing medication
      burden and assuring continuous treatment with full compliance to implant therapy
      as well as having a highly favorable safety profile.

PMID- 24855335
TI  - Effects of zaprinast and rolipram on olfactory and visual memory in the social
      transmission of food preference and novel object recognition tests in mice.
AB  - The role of phosphodiesterase (PDE) inhibitors in central nervous system has been
      investigated and shown to stimulate neuronal functions and increase neurogenesis
      in Alzheimer patients. The aim of this study is to investigate effect of PDE5
      inhibitor zaprinast and PDE4 inhibitor rolipram on visual memory in novel object
      recognition (NOR) test, on olfactory memory in social transmission of food
      preference (STFP) test, and also on locomotion and anxiety in open field test in
      naive mice. Male Balb-c mice were treated intraperitoneally (i.p.) with zaprinast
      (3 and 10 mg/kg), rolipram (0.05 and 0.1 mg/kg), or physiological saline.
      Zaprinast (10 mg/kg) significantly increased cued/non-cued food eaten compared to
      control group, while rolipram had a partial effect on retention trial of STFP
      test. Zaprinast (10 mg/kg) and rolipram (0.05 and 0.1 mg/kg) significantly
      increased ratio index (RI) compared to control group in retention trial of NOR
      test. There was no significant effect of zaprinast and rolipram on total distance
      moved, speed, and center zone duration in open field test. Results of this study
      revealed that both zaprinast and rolipram enhanced visual memory in NOR test,
      however zaprinast exerted a significant memory-enhancing effect compared to
      rolipram in STFP test in mice. 

PMID- 24855337
TI  - Species-Specific Regulation of t-PA and PAI-1 Gene Expression in Human and Rat
      Astrocytes.
AB  - In recent years, the role and physiological regulation of the serine protease
      tissue-type plasminogen activator (t-PA) and its inhibitors, including
      plasminogen activator inhibitor type-1 (PAI-1), in the brain have received much
      attention. However, as studies focusing these issues are difficult to perform in
      humans, a great majority of the studies conducted to date have utilized rodent in
      vivo and/or in vitro models. In view of the species-specific structural
      differences present in both the t-PA and the PAI-1 promoters, we have compared
      the response of these genes in astrocytes of rat and human origin. We reveal
      marked quantitative and qualitative species-specific differences in gene
      induction following treatment with various physiological and pathological
      stimuli. Thus, our findings are of importance for the interpretation of previous
      and future results related to t-PA and PAI-1 expression. 

PMID- 24855339
TI  - How patients experience the surroundings in relation to patient participation: a
      qualitative study of inpatients with intestinal failure.
AB  - INTRODUCTION: Patient participation is known to improve patients' motivation,
      compliance, treatment results, and satisfaction with the received care. It is
      well known that the physical environment is of great importance in supporting
      patient involvement. A systematic literature search has shown a lack of articles
      on the subject of "surroundings" in relation to patient participation, for all
      patient groups. AIM: We aimed to investigate how patients with intestinal failure
      experience their hospital surroundings in relation to patient participation.
      METHODS: The study included eight patients admitted for at least 2 weeks at the
      Intestinal Failure Unit, H8, Salford Royal NHS Foundation Trust, Manchester,
      United Kingdom. Included patients had a good level of consciousness with no
      confusion. The included patients participated in a semistructured interview. The
      interviews were analyzed using Malterud's principles of systematic text
      condensation. RESULTS: The patients described that the surroundings enabled them
      to participate in their treatment and care. The surroundings made it possible for
      them and encouraged them to participate through: the possibility to seek and get
      information and the possibility to participate in daily activities. This led to a
      feeling of independence, reassurance, normality, control, responsibility, and
      confidence. CONCLUSION: The findings in this study indicate that the hospital
      surroundings are essential for the patients with respect to their ability to
      participate in their own care and treatment. The surroundings, in relation to
      patient participation, should be considered when planning and organizing nursing
      care. Further research is needed to increase the understanding of the
      surroundings in relation to patient participation - this research could, for eg,
      include the nurse's perspective.

PMID- 24855338
TI  - Improving anticancer efficacy of (-)-epigallocatechin-3-gallate gold
      nanoparticles in murine B16F10 melanoma cells.
AB  - (-)-Epigallocatechin-3-gallate (EGCG), the major bioactive constituent in green
      tea, has been reported to effectively inhibit the formation and development of
      tumors. To maximize the effectiveness of EGCG, we attached it to nanogold
      particles (EGCG-pNG) in various ratios to examine in vitro cytotoxicity and in
      vivo anti-cancer activity. EGCG-pNG showed improved anti-cancer efficacy in
      B16F10 murine melanoma cells; the cytotoxic effect in the melanoma cells treated
      with EGCG-pNG was 4.91 times higher than those treated with EGCG. The enhancement
      is achieved through mitochondrial pathway-mediated apoptosis as determined by
      annexin V assay, JC-10 staining, and caspase-3, -8, -9 activity assay. Moreover,
      EGCG-pNG was 1.66 times more potent than EGCG for inhibition of tumor growth in a
      murine melanoma model. In the hemolysis assay, the pNG surface conjugated with
      EGCG is most likely the key factor that contributes to the decreased release of
      hemoglobin from human red blood cells. 

PMID- 24855340
TI  - Characterizing weekly self-reported antihypertensive medication nonadherence
      across repeated occasions.
AB  - BACKGROUND: Little is known about weekly variability in medication nonadherence
      both between and within persons. PURPOSE: To characterize medication nonadherence
      across repeated, closely spaced occasions. METHODS: This prospective cohort study
      comprised four unannounced telephone assessment occasions, each separated by
      approximately 2 weeks. On each occasion, adult outpatients taking at least a
      single antihypertensive medication completed a measure of extent of, and reasons
      for, nonadherence. RESULTS: Two hundred and sixty-one participants completed 871
      (83%) of 1,044 occasions. Nonadherence was reported on 152 (17.5%) of 871
      occasions by 93 (36%) of 261 participants. The most commonly endorsed reasons for
      nonadherence were forgetting (39.5%), being busy (23.7%), and traveling (19.7%).
      Among 219 participants completing at least three occasions, 50% of the
      variability in extent of nonadherence was a result of within-person fluctuations,
      and 50% was a result of between-person differences. CONCLUSION: Interventions to
      reduce nonadherence should be informed by variability in the extent of
      nonadherence and specific reasons for nonadherence.

PMID- 24855341
TI  - Comparative outcomes of peripheral nerve blocks versus general anesthesia for hip
      fractures in geriatric Chinese patients.
AB  - BACKGROUND: Geriatric patients undergoing hemiarthroplasty for hip fractures have
      unacceptably high rates of postoperative complications and mortality. Whether
      anesthesia type can affect the outcomes has still been inconclusive. OBJECTIVES:
      We compared general anesthesia (GA) and peripheral nerve blocks (PNBs) on
      postoperative complications and mortality in elderly patients with femoral neck
      fractures (FNF) undergoing hemiarthroplasty. MATERIALS AND METHODS: This
      retrospective study involved data collection from an electronic database. Two
      hundred and seventeen patients underwent hemiarthroplasty for FNF between January
      2008 and December 2012 at the Chinese People's Liberation Army General Hospital.
      Data on mortality within in-hospital, 30-day, and 1-year, complications,
      comorbidities, blood loss and transfusion, operative time, postoperative hospital
      length of stay, intensive care unit admission, and hospital charge were collected
      and analyzed. Univariate and multivariate Cox regression analyses of all
      variables were used for 30-day and 1-year mortality. RESULTS: Seventy-two
      patients receiving GA and 145 receiving PNBs were eventually submitted and
      analyzed. Mortality was 6.9%, 14.7%, and 23.5% at in-hospital, 30-day, and 1
      year, respectively postoperatively, while mortality and cardiovascular
      complications did not differ between the two anesthetic techniques. Preoperative
      comorbidities and intraoperative parameters were not statistically different
      except that patients receiving GA were more likely to have dementia (chi
      (2)=10.45, P=0.001). The most common complications were acute cardiovascular
      events, electrolyte disturbances, and delirium. Postoperative acute respiratory
      events and hypoxemia both were also common, but no differences were found between
      groups (chi (2)=0.68, P=0.410; chi (2)=3.42, P=0.065, respectively). Key factors
      negatively influencing mortality included: age, male gender, American Society of
      Anesthesiologists status, dementia, perioperative cardiovascular events and
      respiratory events, postoperative stroke, myocardial infarction, and hypoxia.
      CONCLUSION: Mortality and postoperative complications are not statistically
      significantly different between PNBs and GA among eldery patients undergoing
      hemiarthroplasty for FNF.

PMID- 24855342
TI  - Do parents of children with attention-deficit/hyperactivity disorder (ADHD)
      receive adequate information about the disorder and its treatments? A qualitative
      investigation.
AB  - BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is the most prevalent
      pediatric neurodevelopmental condition, commonly treated using pharmacological
      agents such as stimulant medicines. The use of these agents remains contentious,
      placing parents in a difficult position when deciding to initiate and/or continue
      their child's treatment. Parents refer to a range of information sources to
      assist with their treatment decision-making. This qualitative study aimed to
      investigate 1) parents' ADHD-related knowledge pre- and post-diagnosis, 2) the
      information sources accessed by parents, 3) whether parents' information needs
      were met post-diagnosis, and 4) parents' views about strategies to meet their
      information needs. METHODS: Three focus groups (n=16 parents), each lasting 1.0
      1.5 hours were conducted. Focus groups were audio-recorded and transcribed
      verbatim. Transcripts were analyzed using the framework method, coded, and
      categorized into themes. RESULTS: Generally, parents had limited ADHD-related
      knowledge prior to their child's diagnosis and perceived prescription medicines
      indicated for ADHD in a negative context. Parents reported improved knowledge
      after their child's diagnosis; however, they expressed dissatisfaction with
      information that they accessed, which was often technical and not tailored to
      their child's needs. Verbal information sought from health care professionals was
      viewed to be reliable but generally medicine-focused and not necessarily
      comprehensive. Parents identified a need for concise, tailored information about
      ADHD, the medicines used for its treatment, and changes to their child's
      medication needs with age. They also expressed a desire for increased
      availability of support groups and tools to assist them in sourcing information
      from health care professionals during consultations, such as question prompt
      lists. CONCLUSION: There are gaps in parents' knowledge about ADHD and its
      treatment, and an expressed need for tailored and reliable information. Future
      research needs to focus on providing parents with avenues to access concise,
      reliable, and relevant information and support in order to empower them to make
      the best treatment decision for their child.

PMID- 24855344
TI  - Impact of hypoglycemia on patients with type 2 diabetes mellitus and their
      quality of life, work productivity, and medication adherence.
AB  - BACKGROUND: The purpose of this study was to determine the characteristics of
      adults with type 2 diabetes mellitus (T2DM) that correlate with greater risk of
      hypoglycemia and determine the impact of hypoglycemia on health-related quality
      of life, work productivity, and medication adherence from a patient perspective.
      METHODS: Data from a large web-based survey were retrospectively analyzed. Adults
      with a diagnosis of T2DM taking antihyperglycemic agents were included in the
      analysis. Participants with knowledge of their hypoglycemic history were divided
      into three groups: those experiencing recent hypoglycemia (previous 3 months),
      those experiencing nonrecent hypoglycemia, and those never experiencing
      hypoglycemia. RESULTS: Of the participants with T2DM taking antihyperglycemic
      agents who were knowledgeable of their hypoglycemia history, 55.7% had ever
      experienced hypoglycemia. Of those, 52.7% had recent hypoglycemia. Compared with
      those who never experienced hypoglycemia, those who experienced hypoglycemia
      tended to: be younger; be more aware of their glycated hemoglobin (HbA1c) levels;
      have higher HbA1c levels; have a higher body mass index; have higher Charlson
      Comorbidity Index scores; be on insulin, sulfonylureas, and/or glucagon-like
      peptide-1 agonists; and be less adherent to their antihyperglycemic agents.
      Hypoglycemia interfered with social activities, caused more missed work
      (absenteeism), more impairment while at work (presenteeism), and decreased
      overall work productivity compared with patients who had never experienced
      hypoglycemia. Overall health-related quality of life, as determined by the Short
      Form-36 health questionnaire, was negatively impacted by hypoglycemia. Both
      Physical and Mental Summary scores were significantly lower for the recent
      hypoglycemia and nonrecent hypoglycemia groups compared with the never
      hypoglycemia group. CONCLUSION: Hypoglycemia can negatively impact many aspects
      of life. Greater awareness of those who are at risk for developing hypoglycemia
      can lead to the development of measures (eg, patient and physician education) to
      prevent future hypoglycemia episodes.

PMID- 24855343
TI  - Coprescription of Chinese herbal medicine and Western medication among female
      patients with breast cancer in Taiwan: analysis of national insurance claims.
AB  - BACKGROUND: Many female breast cancer (FBC) patients take Chinese herbal medicine
      (CHM) and Western medication (WM) concurrently in Taiwan. Despite the possibility
      of interactions between the CHM and WM mentioned in previous studies, the pattern
      of these coprescriptions in FBC patients remains unclear. Hence, the aim of the
      present study is to investigate the utilization of coprescriptions of CHM and WM
      among the FBC patients in Taiwan. METHODS: The study was a cross-sectional survey
      using the sampled cohort in 2009 obtained from the National Health Insurance
      Research Database in Taiwan. There were 3,507 FBC patients identified from the
      registry for catastrophic illness patients. Ambulatory visit records,
      corresponding prescriptions, and the data of beneficiaries belonging to the FBC
      patients were further extracted. A total of 1,086 FBC patients used CHM at least
      once. CHM and WM prescribed within any overlapping duration were defined as
      coprescriptions. RESULTS: There were 868 (80.0%) patients simultaneously
      receiving CHM and WM. A total of 4,927 CHM prescriptions and 6,358 WM
      prescriptions were prescribed concurrently. Among these coprescriptions, the most
      frequently used CHM was jia-wei-xiao-yao-san (21.2%), and the most frequently
      coprescribed WM was acetaminophen (38.9%), followed by tamoxifen (25.5%). There
      were 346 patients using systemic adjuvant therapy and CHM concurrently. The most
      commonly coprescribed CHM with chemotherapy, endocrine therapy, and trastuzumab
      was xiang-sha-liu-jun-zi-tang, jia-wei-xiao-yao-san, and zhi-gan-cao-tang,
      respectively. CONCLUSION: The combined use of CHM with WM is prevalent. The main
      purpose of combining CHM with systemic cancer treatment is to alleviate the
      treatment-related adverse effects. However, the combination may result in the
      potential risk of drug-herb interactions. Further clinical studies are needed to
      evaluate the efficacy and safety of the CHM and WM coprescriptions for FBC
      patients.

PMID- 24855345
TI  - Comparing telehealth-based and clinic-based group cognitive behavioral therapy
      for adults with depression and anxiety: a pilot study.
AB  - BACKGROUND: The primary objective of this pilot study was to demonstrate reliable
      adherence to a group cognitive behavioral (CBT) therapy protocol when delivered
      using on-line video conferencing as compared with face-to-face delivery of group
      CBT. A secondary aim was to show comparability of changes in subject depression
      inventory scores between on-line and face-to-face delivery of group CBT. METHODS:
      We screened 31 individuals, 18 of whom met the criteria for a DSM-IV (Diagnostic
      and Statistical Manual of Mental Disorders, 4th Edition) diagnosis of mood and/or
      anxiety disorder. All qualifying participants had the necessary equipment
      (computer, webcam, Internet) for participation in the study, but could exercise
      their preference for either the on-line or face-to-face format. Eighteen
      completed the 13 weekly session intervention program (ten face-to-face; eight
      video conferencing). We coded adherence to protocol in both intervention formats
      and generated pre-post changes in scores on the Beck Depression Inventory Second
      Edition (BDI-II) for each participant. RESULTS: Application of the CBT protocol
      coding system showed reliable adherence to the group CBT intervention protocol in
      both delivery formats. Similarly, qualitative analysis of the themes in group
      discussion indicated that both groups addressed similar issues. Pre-post
      intervention scores for the BDI-II were comparable across the two delivery
      formats, with 60% of participants in each group showing a positive change in BDI
      II severity classification (eg, from moderate to low symptoms). CONCLUSION: This
      pilot study demonstrates that group CBT could be delivered in a technology
      supported environment (on-line video conferencing) and can meet the same
      professional practice standards and outcomes as face-to-face delivery of the
      intervention program.

PMID- 24855346
TI  - Can medical insurance coverage reduce disparities of income in elderly patients
      requiring long-term care? The case of the People's Republic of China.
AB  - BACKGROUND: The People's Republic of China's population is aging rapidly, partly
      because of the impact of the one-child policy and improvements in the health care
      system. Caring for bedridden seniors can be a challenge for many families in the
      People's Republic of China. OBJECTIVE: To identify the inequality of income among
      different age groups and social statuses, and evaluate the medical burden and
      health insurance compensation in the People's Republic of China. METHODS: We
      measured income inequality and insurance compensation levels among bedridden
      patients in Zhejiang province, People's Republic of China. Factor analysis and
      Gini coefficients were used to evaluate degree of income inequality and insurance
      compensation level. RESULTS: We found distinct regional disparities in Zhejiang
      province, including the aspects of income, expenses, and time. Gini coefficients
      of older adults with long-term care needs in urban and rural areas were 0.335 and
      0.602, respectively. In all age groups, Gini coefficients increased after
      adjustment for medical expenditures, and the inequality persisted after insurance
      reimbursement was taken into consideration. CONCLUSION: A significant income
      disparity between rural and urban areas was observed. Inequality increased with
      age, and medical expenditure is a huge burden for older people with long-term
      care needs. Health insurance does not play an important role in reducing
      inequalities among patients who need long-term care services.

PMID- 24855347
TI  - Psychological well-being in individuals with mild cognitive impairment.
AB  - OBJECTIVES: Cognitive impairments associated with aging and dementia are major
      sources of burden, deterioration in life quality, and reduced psychological well
      being (PWB). Preventative measures to both reduce incident disease and improve
      PWB in those afflicted are increasingly targeting individuals with mild cognitive
      impairment (MCI) at early disease stage. However, there is very limited
      information regarding the relationships between early cognitive changes and
      memory concern, and life quality and PWB in adults with MCI; furthermore, PWB
      outcomes are too commonly overlooked in intervention trials. The purpose of this
      study was therefore to empirically test a theoretical model of PWB in MCI in
      order to inform clinical intervention. METHODS: Baseline data from a convenience
      sample of 100 community-dwelling adults diagnosed with MCI enrolled in the Study
      of Mental Activity and Regular Training (SMART) trial were collected. A series of
      regression analyses were performed to develop a reduced model, then hierarchical
      regression with the Baron Kenny test of mediation derived the final three-tiered
      model of PWB. RESULTS: Significant predictors of PWB were subjective memory
      concern, cognitive function, evaluations of quality of life, and negative affect,
      with a final model explaining 61% of the variance of PWB in MCI. DISCUSSION: Our
      empirical findings support a theoretical tiered model of PWB in MCI and
      contribute to an understanding of the way in which early subtle cognitive
      deficits impact upon PWB. Multiple targets and entry points for clinical
      intervention were identified. These include improving the cognitive difficulties
      associated with MCI. Additionally, these highlight the importance of reducing
      memory concern, addressing low mood, and suggest that improving a person's
      quality of life may attenuate the negative effects of depression and anxiety on
      PWB in this cohort.

PMID- 24855348
TI  - Relationship between falls, knee osteoarthritis, and health-related quality of
      life: data from the Osteoarthritis Initiative study.
AB  - BACKGROUND: The purpose of this study was to examine the relationship between
      self-reported falls, doctor-diagnosed knee osteoarthritis (OA), and health
      related quality of life (HRQoL). We hypothesized that falls and knee OA would be
      associated with poor HRQoL on both disease-specific and generic measures.
      METHODS: This cross-sectional study used data from the publicly available
      Osteoarthritis Initiative data sets. A total of 4,484 subjects aged 45-79 years
      at baseline were divided into three subpopulations: those who had neither a
      history of falling nor doctor-diagnosed knee OA; those who had either a self
      reported history of falling or doctor-diagnosed knee OA; and those who had both a
      self-reported history of falling and doctor-diagnosed knee OA. HRQoL was assessed
      using both disease-specific and generic measures. Multiple regression analyses
      were used to examine the relationship between self-reported falls, doctor
      diagnosed knee OA, and HRQoL assessed using the Knee Injury and Osteoarthritis
      Outcome Score-Quality of Life (KOOS-QoL) subscale and two Short Form-12 (SF-12)
      summary scales. The models were adjusted for participant sociodemographic,
      lifestyle, and clinical characteristics. RESULTS: Falls and knee OA were
      significantly associated with lower scores on the KOOS-QoL (beta= -34.4, standard
      error 2.27, P<=0.0001) and on the physical component scale of the SF-12 (beta= 
      9.44, standard error 0.90, P<0.0001). No significant relationship was found with
      the mental component scale score when adjusted for sociodemographic, lifestyle,
      and clinical characteristics. CONCLUSION: When compared with those having neither
      a self-reported history of falling nor doctor-diagnosed knee OA and those with a
      self-reported history of falling or doctor-diagnosed knee OA, persons with both
      conditions (falls and knee OA) had significantly lower KOOS-QoL and physical
      component scale scores after adjusting for sociodemographic, lifestyle, and
      clinical characteristics. Future research should assess potential mediating
      factors in an effort to improve HRQoL in persons with knee OA who are at high
      risk of falling.

PMID- 24855349
TI  - Acceptance of an assistive robot in older adults: a mixed-method study of human
      robot interaction over a 1-month period in the Living Lab setting.
AB  - BACKGROUND: There is growing interest in investigating acceptance of robots,
      which are increasingly being proposed as one form of assistive technology to
      support older adults, maintain their independence, and enhance their well-being.
      In the present study, we aimed to observe robot-acceptance in older adults,
      particularly subsequent to a 1-month direct experience with a robot. SUBJECTS AND
      METHODS: Six older adults with mild cognitive impairment (MCI) and five
      cognitively intact healthy (CIH) older adults were recruited. Participants
      interacted with an assistive robot in the Living Lab once a week for 4 weeks.
      After being shown how to use the robot, participants performed tasks to simulate
      robot use in everyday life. Mixed methods, comprising a robot-acceptance
      questionnaire, semistructured interviews, usability-performance measures, and a
      focus group, were used. RESULTS: Both CIH and MCI subjects were able to learn how
      to use the robot. However, MCI subjects needed more time to perform tasks after a
      1-week period of not using the robot. Both groups rated similarly on the robot
      acceptance questionnaire. They showed low intention to use the robot, as well as
      negative attitudes toward and negative images of this device. They did not
      perceive it as useful in their daily life. However, they found it easy to use,
      amusing, and not threatening. In addition, social influence was perceived as
      powerful on robot adoption. Direct experience with the robot did not change the
      way the participants rated robots in their acceptance questionnaire. We
      identified several barriers to robot-acceptance, including older adults'
      uneasiness with technology, feeling of stigmatization, and ethical/societal
      issues associated with robot use. CONCLUSION: It is important to destigmatize
      images of assistive robots to facilitate their acceptance. Universal design
      aiming to increase the market for and production of products that are usable by
      everyone (to the greatest extent possible) might help to destigmatize assistive
      devices.

PMID- 24855350
TI  - Risk of pneumonia with inhaled corticosteroid/long-acting beta2 agonist therapy
      in chronic obstructive pulmonary disease: a cluster analysis.
AB  - BACKGROUND: Pneumonia poses a significant risk in patients with moderate to
      severe chronic obstructive pulmonary disease but data are limited on the disease
      phenotypes most susceptible to pneumonia. METHODS: Cluster analysis using a data
      driven recursive partitioning algorithm was employed using baseline data from two
      pooled one-year randomized exacerbation trials (n=3,255) of fluticasone
      furoate/vilanterol or vilanterol alone to identify distinct patient groups at
      greatest risk of pneumonia or serious (hospitalization or death) pneumonia.
      RESULTS: Five clusters were identified. Patients at greater risk of first
      pneumonia had more severe obstruction (forced expiratory volume in one
      second/forced vital capacity <46%) and either a body mass index <19 kg/m(2)
      (hazard ratio 7.8, 95% confidence interval 4.7-13.0; n=144) or a pneumonia
      history and greater comorbidities (hazard ratio 4.8, 95% confidence interval 3.0
      7.7; n=374) relative to the cluster with the lowest pneumonia risk (reference;
      n=1310). Multiple comorbidities and use of psychoanaleptics also contributed to
      an increased risk of pneumonia in more obstructed patients. Independent of
      cluster, use of inhaled corticosteroids was associated with pneumonia (hazard
      ratio 1.89, 95% confidence interval 1.25-2.84) and serious pneumonia (hazard
      ratio 2.92, 95% confidence interval 1.40-6.01). CONCLUSION: Cluster analysis can
      identify patient populations at risk for serious safety outcomes and inform risk
      management strategies to optimize patient management. The greatest risk for
      pneumonia was in subjects with multiple pneumonia risk factors.

PMID- 24855351
TI  - Preparation and properties of BSA-loaded microspheres based on multi-(amino acid)
      copolymer for protein delivery.
AB  - A multi-(amino acid) copolymer (MAC) based on omega-aminocaproic acid, gamma
      aminobutyric acid, L-alanine, L-lysine, L-glutamate, and hydroxyproline was
      synthetized, and MAC microspheres encapsulating bovine serum albumin (BSA) were
      prepared by a double-emulsion solvent extraction method. The experimental results
      show that various preparation parameters including surfactant ratio of Tween 80
      to Span 80, surfactant concentration, benzyl alcohol in the external water phase,
      and polymer concentration had obvious effects on the particle size, morphology,
      and encapsulation efficiency of the BSA-loaded microspheres. The sizes of BSA
      loaded microspheres ranged from 60.2 MUm to 79.7 MUm, showing different degrees
      of porous structure. The encapsulation efficiency of BSA-loaded microspheres also
      ranged from 38.8% to 50.8%. BSA release from microspheres showed the classic
      biphasic profile, which was governed by diffusion and polymer erosion. The
      initial burst release of BSA from microspheres at the first week followed by
      constant slow release for the next 7 weeks were observed. BSA-loaded microspheres
      could degrade gradually in phosphate buffered saline buffer with pH value
      maintained at around 7.1 during 8 weeks incubation, suggesting that microsphere
      degradation did not cause a dramatic pH drop in phosphate buffered saline buffer
      because no acidic degradation products were released from the microspheres.
      Therefore, the MAC microspheres might have great potential as carriers for
      protein delivery. 

PMID- 24855352
TI  - Self-assembled or mixed peptide amphiphile micelles from Herpes simplex virus
      glycoproteins as potential immunomodulatory treatment.
AB  - The use of micelle aggregates formed from peptide amphiphiles (PAs) as potential
      synthetic self-adjuvant vaccines to treat Herpes simplex virus (HSV) infection
      are reported here. The PAs were based on epitopes gB409-505 and gD301-309,
      selected from HSV envelope glycoprotein B (gB) and glycoprotein D (gD), that had
      their N-terminus modified with hydrophobic moieties containing two C18
      hydrocarbon chains. Pure and mixed micelles of gB and/or gD peptide epitopes were
      easily prepared after starting with the synthesis of corresponding PAs by solid
      phase methods. Structural characterization of the aggregates confirmed that they
      were sufficiently stable and compatible with in vivo use: critical micelle
      concentration values around 4.0 ? 10(-7) mol ? Kg(-1); hydrodynamic radii (RH)
      between 50-80 nm, and a zeta potential (zeta) around - 40 mV were found for all
      aggregates. The in vitro results indicate that both peptide epitopes and
      micelles, at 10 MUM, triggered U937 and RAW 264.7 cells to release appreciable
      levels of cytokines. In particular, interleukin (IL)-23-, IL-6-, IL-8- or
      macrophage inflammatory protein (MIP)-2-, and tumor necrosis factor (TNF)-alpha
      release increased considerably when cells were treated with the gB-micelles or gD
      micelles compared with the production of the same cytokines when the stimulus was
      the single gB or gD peptide. 

PMID- 24855353
TI  - Enhanced uptake and transport of (+)-catechin and (-)-epigallocatechin gallate in
      niosomal formulation by human intestinal Caco-2 cells.
AB  - The aim of this study was to evaluate (+)-catechin and (-)-epigallocatechin
      gallate (EGCG) cellular uptake and transport across human intestinal Caco-2 cell
      monolayer in both the absence and presence of niosomal carrier in variable
      conditions. The effect of free drugs and drug-loaded niosomes on the growth of
      Caco-2 cells was studied. The effects of time, temperature, and concentration on
      drug cellular uptake in the absence or presence of its niosomal delivery systems
      were investigated. The intestinal epithelial membrane transport of the drug
      loaded niosomes was examined using the monolayer of the human Caco-2 cells. The
      kinetics of transport, and the effect of temperature, adenosine triphosphate
      inhibitor, permeability glycoprotein inhibitor, multidrug resistance-associated
      protein 2 inhibitor, and the absorption enhancer on transport mechanism were
      investigated. It was found that the uptake of catechin, EGCG, and their niosomes
      by Caco-2 cells was 1.22 +/- 0.16, 0.90 +/- 0.14, 3.25 +/- 0.37, and 1.92 +/-
      0.22 MUg/mg protein, respectively (n=3). The apparent permeability coefficient
      values of catechin, EGCG, and their niosomes were 1.68 +/- 0.16, 0.88 +/- 0.09,
      2.39 +/- 0.31, and 1.42 +/- 0.24 cm/second (n=3) at 37 degrees C, respectively.
      The transport was temperature- and energy-dependent. The inhibitors of
      permeability glycoprotein and multidrug resistance-associated protein 2 and the
      absorption enhancer significantly enhanced the uptake amount. Compared with the
      free drugs, niosomal formulation significantly enhanced drug absorption.
      Additionally, drug-loaded niosomes exhibited stronger stability and lower
      toxicity. These findings showed that the oral absorption of tea flavonoids could
      be improved by using the novel drug delivery systems.

PMID- 24855354
TI  - Folate receptor-targeted liposomes enhanced the antitumor potency of imatinib
      through the combination of active targeting and molecular targeting.
AB  - PURPOSE: Imatinib inhibits platelet-derived growth factor receptor (PDGFR), and
      evidence shows that PDGFR participates in the development and progression of
      cervical cancer. Although imatinib has exhibited preclinical activity against
      cervical cancer, only minimal clinical therapeutic efficacy was observed. This
      poor therapeutic efficacy may be due to insufficient drug delivery to the tumor
      cells and plasma protein binding. Therefore, the purpose of this study was to
      explore a novel folate receptor (FR)-targeted delivery system via imatinib-loaded
      liposomes to enhance drug delivery to tumor cells and to reduce plasma protein
      binding. METHODS: Imatinib was remote-loaded into FR-targeted liposomes which
      were prepared by thin film hydration followed by polycarbonate membrane
      extrusion. Encapsulation efficiency, mean size diameter, and drug retention were
      characterized and cellular uptake, cell cytotoxicity, and cell apoptosis on
      cervical cancer HeLa cells were evaluated. Comparative pharmacokinetic studies
      were also carried out with FR-targeted imatinib liposomes, simple imatinib
      liposomes, and free imatinib. RESULTS: High encapsulation efficiency (>90%),
      appropriate mean particle size (143.5 nm), and zeta potential (-15.97 mV) were
      obtained for FR-targeted imatinib liposomes. The drug release profile showed
      minimal imatinib leakage (<5%) in phosphate-buffered saline (PBS) at pH =7.4
      within 72 hours of incubation, while more leakage (>25%) was observed in PBS at
      pH =5.5. This indicates that these liposomes possess a certain degree of pH
      sensitivity. Cytotoxicity assays demonstrated that the FR-targeted imatinib
      liposomes promoted a six-fold IC50 reduction on the non-targeted imatinib
      liposomes from 910 to 150 MUM. In addition, FR-targeted imatinib liposomes
      enhanced HeLa cell apoptosis in vitro compared to the non-targeted imatinib
      liposomes. Pharmacokinetic parameters indicated that both targeted and non
      targeted liposomes exhibited long circulation properties in Kunming mice.
      CONCLUSION: These findings indicate that the nano-sized FR-targeted PDGFR
      antagonist imatinib liposomes may constitute a promising strategy in cervical
      cancer therapy through the combination of active targeting and molecular
      targeting.

PMID- 24855355
TI  - Efficiently engineered cell sheet using a complex of polyethylenimine-alginate
      nanocomposites plus bone morphogenetic protein 2 gene to promote new bone
      formation.
AB  - Regeneration of large bone defects is a common clinical problem. Recently, stem
      cell sheet has been an emerging strategy in bone tissue engineering. To enhance
      the osteogenic potential of stem cell sheet, we fabricated bone morphogenetic
      protein 2 (BMP-2) gene-engineered cell sheet using a complex of polyethylenimine
      alginate (PEI-al) nanocomposites plus human BMP-2 complementary(c)DNA plasmid,
      and studied its osteogenesis in vitro and in vivo. PEI-al nanocomposites carrying
      BMP-2 gene could efficiently transfect bone marrow mesenchymal stem cells. The
      cell sheet was made by culturing the cells in medium containing vitamin C for 10
      days. Assays on the cell culture showed that the genetically engineered cells
      released the BMP-2 for at least 14 days. The expression of osteogenesis-related
      gene was increased, which demonstrated that released BMP-2 could effectively
      induce the cell sheet osteogenic differentiation in vitro. To further test the
      osteogenic potential of the cell sheet in vivo, enhanced green fluorescent
      protein or BMP-2-producing cell sheets were treated on the cranial bone defects.
      The results indicated that the BMP-2-producing cell sheet group was more
      efficient than other groups in promoting bone formation in the defect area. Our
      results suggested that PEI-al nanocomposites efficiently deliver the BMP-2 gene
      to bone marrow mesenchymal stem cells and that BMP-2 gene-engineered cell sheet
      is an effective way for promoting bone regeneration. 

PMID- 24855356
TI  - Aneuploidogenic effects and DNA oxidation induced in vitro by differently sized
      gold nanoparticles.
AB  - Gold nanoparticles (Au NPs) are used in many fields, including biomedical
      applications; however, no conclusive information on their potential cytotoxicity
      and genotoxicity mechanisms is available. For this reason, experiments in human
      primary lymphocytes and murine macrophages (Raw264.7) were performed exposing
      cells to spherical citrate-capped Au NPs with two different nominal diameters (5
      nm and 15 nm). The proliferative activity, mitotic, apoptotic, and necrotic
      markers, as well as chromosomal damage were assessed by the cytokinesis-block
      micronucleus cytome assay. Fluorescence in situ hybridization with human and
      murine pancentromeric probes was applied to distinguish between clastogenic and
      aneuploidogenic effects. Our results indicate that 5 nm and 15 nm Au NPs are able
      to inhibit cell proliferation by apoptosis and to induce chromosomal damage, in
      particular chromosome mis-segregation. DNA strand breaks were detected by comet
      assay, and the modified protocol using endonuclease-III and formamidopyrimidine
      DNA glycosylase restriction enzymes showed that pyrimidines and purines were
      oxidatively damaged by Au NPs. Moreover, we show a size-independent correlation
      between the cytotoxicity of Au NPs and their tested mass concentration or
      absolute number, and genotoxic effects which were more severe for Au NP 15 nm
      compared to Au NP 5 nm. Results indicate that apoptosis, aneuploidy, and DNA
      oxidation play a pivotal role in the cytotoxicity and genotoxicity exerted by Au
      NPs in our cell models. 

PMID- 24855357
TI  - Interaction between immobilized polyelectrolyte complex nanoparticles and human
      mesenchymal stromal cells.
AB  - BACKGROUND: Implant loosening or deficient osseointegration is a major problem in
      patients with systemic bone diseases (eg, osteoporosis). For this reason, the
      stimulation of the regional cell population by local and sustained drug delivery
      at the bone/implant interface to induce the formation of a mechanical stable bone
      is promising. The purpose of this study was to investigate the interaction of
      polymer-based nanoparticles with human bone marrow-derived cells, considering
      nanoparticles' composition and surface net charge. MATERIALS AND METHODS:
      Polyelectrolyte complex nanoparticles (PECNPs) composed of the polycations
      poly(ethyleneimine) (PEI), poly(L-lysine) (PLL), or (N,N
      diethylamino)ethyldextran (DEAE) in combination with the polyanions dextran
      sulfate (DS) or cellulose sulfate (CS) were prepared. PECNPs' physicochemical
      properties (size, net charge) were characterized by dynamic light scattering and
      particle charge detector measurements. Biocompatibility was investigated using
      human mesenchymal stromal cells (hMSCs) cultured on immobilized PECNP films (5-50
      nmol.cm(-2)) by analysis for metabolic activity of hMSCs in dependence of PECNP
      surface concentration by MTS (3-[4,5-dimethylthiazol-2-yl]-5-[3
      carboxymethoxyphenyl]-2-[4-sulfophenyl]-2H-tetrazolium, inner salt) assay, as
      well as cell morphology (phase contrast microscopy). RESULTS: PECNPs ranging
      between ~50 nm and 150 nm were prepared. By varying the ratio of polycations and
      polyanions, PECNPs with a slightly positive (PEC(+)NP) or negative (PEC(-)NP) net
      charge were obtained. The PECNP composition significantly affected cell
      morphology and metabolic activity, whereas the net charge had a negligible
      influence. Therefore, we classified PECNPs into "variant systems" featuring a
      significant dose dependency of metabolic activity (DEAE/CS, PEI/DS) and
      "invariant systems" lacking such a dependency (DEAE/DS, PEI/CS).
      Immunofluorescence imaging of fluorescein isothiocyanate isomer I (FITC)-labeled
      PECNPs suggested internalization into hMSCs remaining stable for 8 days.
      CONCLUSION: Our study demonstrated that PECNP composition affects hMSC behavior.
      In particular, the PEI/CS system showed biocompatibility in a wide concentration
      range, representing a suitable system for local drug delivery from PECNP
      functionalized bone substitute materials.

PMID- 24855359
TI  - Psychiatry 2050: from younger psychiatrists' perspective.

PMID- 24855358
TI  - Gold-functionalized magnetic nanoparticles restrict growth of Pseudomonas
      aeruginosa.
AB  - Superparamagnetic iron oxide nanoparticles (SPIONs) and their derivatives
      (aminosilane and gold-coated) have been widely investigated in numerous medical
      applications, including their potential to act as antibacterial drug carriers
      that may penetrate into bacteria cells and biofilm mass. Pseudomonas aeruginosa
      is a frequent cause of infection in hospitalized patients, and significant
      numbers of currently isolated clinical strains are resistant to standard
      antibiotic therapy. Here we describe the impact of three types of SPIONs on the
      growth of P. aeruginosa during long-term bacterial culture. Their size,
      structure, and physicochemical properties were determined using transmission
      electron microscopy, X-ray diffraction analysis, and Fourier transform infrared
      spectroscopy. We observed significant inhibition of P. aeruginosa growth in
      bacterial cultures continued over 96 hours in the presence of gold-functionalized
      nanoparticles (Fe3O4@Au). At the 48-hour time point, growth of P. aeruginosa, as
      assessed by the number of colonies grown from treated samples, showed the highest
      inhibition (decreased by 40%). These data provide strong evidence that Fe3O4@Au
      can dramatically reduce growth of P. aeruginosa and provide a platform for
      further study of the antibacterial activity of this nanomaterial.

PMID- 24855361
TI  - Effects of quetiapine and olanzapine in patients with psychosis and violent
      behavior: a pilot randomized, open-label, comparative study.
AB  - OBJECTIVE: Patients suffering from psychosis are more likely than the general
      population to commit aggressive acts, but the therapeutics of aggressive behavior
      are still a matter of debate. METHODS: This pilot randomized, open-label study
      compared the efficacy of quetiapine versus olanzapine in reducing impulsive and
      aggressive behaviors (primary endpoints) and psychotic symptoms (secondary
      endpoints) from baseline to days 1, 7, 14, 28, 42, 56, and 70, in 15 violent
      schizophrenic patients hospitalized in a maximum-security psychiatric hospital.
      RESULTS: Quetiapine (525+/-45 mg) and olanzapine (18.5+/-4.8 mg) were both
      efficacious in reducing Impulsivity Rating Scale from baseline to day 70. In
      addition, both treatments reduced the Brief Psychiatric Rating Scale, Positive
      and Negative Syndrome Scale, and Clinical Global Impression Scale scores at day
      70 compared to baseline, and no differences were observed between treatments.
      Moreover, quetiapine, but not olanzapine, yielded an improvement of depressive
      symptoms in the items "depression" in Brief Psychiatric Rating Scale and "blunted
      affect" in Positive and Negative Syndrome Scale. Modified Overt Aggression Scale
      scores were also decreased from baseline to the endpoint, but due to the limited
      number of patients, it was not possible to detect a significant difference.
      CONCLUSION: In this pilot study, quetiapine and olanzapine equally decreased
      impulsive and psychotic symptoms after 8 weeks of treatment. Double-blind, large
      studies are needed to confirm the validity of these two treatments in highly
      aggressive and violent schizophrenic patients.

PMID- 24855360
TI  - More female patients and fewer stimuli per session are associated with the short
      term antidepressant properties of repetitive transcranial magnetic stimulation
      (rTMS): a meta-analysis of 54 sham-controlled studies published between 1997
      2013.
AB  - BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) of the
      dorsolateral prefrontal cortex (DLPFC) appears to have short-term antidepressant
      properties. The aim of the current study was to update our previous meta-analysis
      and to investigate factors associated with the antidepressant properties of rTMS.
      METHOD: Following a systematic literature search conducted in Medline and
      PsycInfo, N=14 sham-controlled, parallel design studies (published after 2008 to
      August 2013) that had utilized rTMS of the DLPFC in major depression were
      included in the current meta-analysis. The sensitivity and moderator analyses
      also included data from N=40 studies (published in 1997-2008) from our previous
      meta-analysis. The effect size (Cohen's d) in each study was the standardized
      difference in mean depression scores (on Hamilton Depression Rating Scale, Beck
      Depression Inventory, Montgomery Asberg Depression Rating Scale) from baseline to
      final (after last session) in rTMS compared to sham groups. RESULTS: According to
      a random-effects model with inverse-variance weights, depression scores were
      significantly reduced after rTMS compared to sham in studies published from 2008
      2013 based on N=659 patients (overall mean weighted d=-0.42, 95% confidence
      interval: -0.66, -0.18, P=0.001). Combining studies from our past and current
      meta-analyses (published in 1997-2013; N=54) revealed that depression was
      significantly reduced after left-fast (>1 Hz), right-slow (<=1 Hz), and bilateral
      (or sequential) rTMS of DLPFC compared to sham. Significant antidepressant
      properties of rTMS were observed in studies with patients who were treatment
      resistant, unipolar (or bipolar), non-psychotic, medication-free (or started on
      antidepressants concurrently with rTMS). According to univariate meta
      regressions, depression scores were significantly lower in studies with more
      female patients and fewer stimuli per session. There was little evidence that
      publication bias occurred in the analysis. CONCLUSION: According to this study,
      the largest meta-analysis to date, short-term antidepressant properties of rTMS
      are independent of concurrent antidepressants and might depend on sex and the
      number of stimuli per session.

PMID- 24855362
TI  - Nonergot dopamine-receptor agonists for treating Parkinson's disease - a network
      meta-analysis.
AB  - OBJECTIVE: To compare the efficacy of the three nonergot dopamine-receptor
      agonists (DAs) pramipexole, ropinirole, and rotigotine for the treatment of early
      and advanced Parkinson's disease (PD). MATERIALS AND METHODS: Bayesian network
      meta-analyses were performed separately for early and advanced PD, and at time
      points 11-16 and 24-28 weeks. Outcomes for early PD included improvement on the
      Unified Parkinson's Disease Rating Scale (UPDRS) activities in daily life (UPDRS
      II), motor function (UPDRS-III), and their subtotal (UPDRS-II + III). Outcomes
      for advanced PD also included daily "off time" (hours), but not UPDRS-II + III.
      RESULTS: Totals of 23 and 24 trials informed early and advanced PD analyses. For
      early PD UPDRS-II at 11-16 weeks, pramipexole and rotigotine were statistically
      significantly superior to placebo, but ropinirole was not. For UPDRS-III and
      UPDRS-II + III, all DAs were statistically significantly better than placebo and
      exhibited similar improvements. At 24-28 weeks, results were also statistically
      significant for all DAs versus placebo, and the magnitudes of improvements were
      similar for pramipexole, ropinirole and rotigotine. Advanced PD improvements on
      UPDRS-II, UPRDS-III, and off time were statistically significant for pramipexole,
      ropinirole, and rotigotine versus placebo. At 11-16 weeks, rotigotine yielded
      slightly smaller effects than ropinirole and pramipexole, but credible intervals
      on differences were wide. For off time, results were near identical. At 24-28
      weeks, results were similar for all three outcomes. Ropinirole yielded a slightly
      higher improvement on UPDRS-III, but a slightly smaller improvement in off time.
      CONCLUSION: Our analyses suggest that pramipexole, ropinirole, and rotigotine
      exhibit similar efficacy in the treatment of early and advanced PD.

PMID- 24855364
TI  - The prevalence of bipolar spectrum disorder in elderly patients with recurrent
      depression.
AB  - PURPOSE: Despite a growing body of knowledge on bipolar spectrum disorder (BSD),
      relatively little is known about the clinical characteristics of BSD in elderly
      people. We investigated the prevalence of BSD in elderly patients with recurrent
      depression. PATIENTS AND METHODS: A total of 65 elderly outpatients (>=60 years
      of age) who met the Diagnostic and Statistical Manual of Mental Disorders IV
      criteria for recurrent major depressive disorder participated in the study. BSD
      was diagnosed according to the criteria developed by Ghaemi et al and the Mood
      Disorder Questionnaire (MDQ) was used to assess bipolarity. RESULTS: Of 65
      subjects, eleven (16.9%) and 54 (83.1%) were diagnosed with BSD and unipolar
      depression, respectively. A total of 32.3% (n=22) had a positive screen for
      bipolar disorder, and we found a significant association between the BSD criteria
      and the criteria for a positive MDQ (P<0.001). Patients with BSD had a longer
      duration of illness (P=0.040) and more prior depressive episodes (P<0.001) than
      did those with unipolar depression. The BSD criteria of first-degree relative
      with bipolar disorder (P=0.030), antidepressant-induced hypomania (P=0.034),
      hyperthymic personality (P=0.001), and atypical depression (P=0.030) were highly
      associated with MDQ-positive patients. CONCLUSION: Our results indicate that many
      depressed elderly patients have bipolar-related illness; moreover, some features
      of the depression are associated with bipolarity.

PMID- 24855366
TI  - Tension-free repair during extensive radical surgery for cecal cancer with
      abdominal wall invasion and inguinal lymph node metastasis.
AB  - We report a case of cecal cancer with invasion of the abdominal wall and right
      inguinal lymph node metastasis. This patient had undergone an appendectomy 2
      years previously. He underwent extensive radical right hemicolectomy with
      anastomosis and tension-free repair of the damaged right lower abdominal wall.
      The surgery progressed successfully, and the vital signs of the patient were
      stable (approximately 200 mL blood loss). Postoperative diagnosis revealed
      moderately to poorly differentiated adenocarcinoma of the cecum with invasion of
      the abdominal wall and metastasis of the inguinal lymph nodes (pT4bN2bM1, IV4a).
      The patient has remained well post-surgery. 

PMID- 24855363
TI  - Addressing the unmet needs of patients with persistent negative symptoms of
      schizophrenia: emerging pharmacological treatment options.
AB  - The negative symptoms of schizophrenia represent an impairment of normal
      emotional responses, thought processes and behaviors, and include blunting or
      flattening of affect, alogia/aprosody, avolition/apathy, anhedonia, and
      asociality. Negative symptoms contribute to a reduced quality of life, increased
      functional disability, increased burden of illness, and poorer long-term
      outcomes, to a greater degree than positive symptoms. Primary negative symptoms
      are prominent and persistent in up to 26% of patients with schizophrenia, and
      they are estimated to occur in up to 58% of outpatients at any given time.
      Negative symptoms respond less well to medications than positive symptoms, and to
      date treatment options for negative symptoms have been limited, with no accepted
      standard treatment. Modest benefits have been reported with a variety of
      different agents, including second-generation antipsychotics and add-on therapy
      with antidepressants and other pharmacological classes. Recent clinical research
      focusing on negative symptoms target novel biological systems, such as
      glutamatergic neurotransmission. Different approaches include: enhancing N-methyl
      D-aspartate receptor function with agents that bind directly to the glycine
      ligand site or with glycine reuptake inhibitors; influencing the metabotropic
      glutamate receptor (mGluR2/3) with positive allosteric modulators; and
      stimulating nicotinic acetylcholine receptors. In conclusion, the lack of clearly
      efficacious pharmacological treatments for the management of negative symptoms
      represents a significant unmet need, especially considering the importance of
      these symptoms on patient outcomes. Hence, further research to identify and
      characterize novel pharmacological treatments for negative symptoms is greatly
      needed. 

PMID- 24855365
TI  - Primary or secondary antifungal prophylaxis in patients with hematological
      maligancies: efficacy and damage.
AB  - BACKGROUND: Patients with hematological malignancies often develop febrile
      neutropenia (FN) as a complication of cancer chemotherapy. Primary or secondary
      antifungal prophylaxis is recommended for patients with hematological
      malignancies to reduce the risk of invasive fungal infection (IFI). This study
      retrospectively evaluated the efficacy and potential harm of administration of
      primary and secondary antifungal prophylaxis to patients with hematological
      malignancies at one hospital. METHODS: All patients with hematological
      malignancies older than 14 years of age who had experienced at least one FN
      attack during chemotherapy while being treated at one hospital between November
      2010 and November 2012 were retrospectively evaluated. RESULTS: A total of 282 FN
      episodes in 126 consecutive patients were examined during a 2-year study period.
      The mean patient age was 51.73+/-14.4 years (range: 17-82 years), and 66 patients
      were male. Primary prophylaxis with posaconazole was administered to 13 patients
      and systemic antifungal treatment under induction or consolidation chemotherapy
      to seven patients. Of 26 patients who received secondary antifungal prophylaxis
      with either oral voriconazole (n=17) or posaconazole (n=6) during 46 FN episodes,
      systemic antifungal therapy was administered in 16 of 38 episodes and three of
      eight episodes, respectively. Secondary antifungal prophylaxis with caspofungin
      was found effective in treating six FN episodes in three patients who had
      experienced at least two persistent candidemia attacks. The mortality rates
      associated with IFI were 9% in the first year, 2% in the second year, and 6%
      overall. The mortality rates associated with candidemia were 33% in the first
      year, 22% in the second year, and 27% overall. CONCLUSION: Primary antifungal
      prophylaxis should be administered to selected patients on the basis of
      consideration of efficacy, cost, and potential harm. Use of secondary prophylaxis
      may reduce systemic antifungal use and IFI frequency but may increase risk of
      colonization and infection with azole-resistant fungal strains.

PMID- 24855367
TI  - Experimental study of tissue-engineered cartilage allograft with RNAi
      chondrocytes in vivo.
AB  - PURPOSE: To determine the effects of RNA interference (RNAi) on chondrocyte
      proliferation, function, and immunological rejection after allogenic tissue
      engineered cartilage transplantation within bone matrix gelatin scaffolds.
      METHODS: Seven million rat normal and RNAi chondrocytes were harvested and
      separately composited with fibrin glue to make the cell suspension, and then
      transplanted subcutaneously into the back of Sprague Dawley rats after being
      cultured for 10 days in vitro. Untransplanted animals served as the control
      group. The allograft and immunological response were examined at 1, 2, 4, 8, and
      12 months postoperatively with hematoxylin and eosin histochemical staining,
      immunohistochemical staining (aggrecan, type II collagen, class I and II major
      histocompatibility complex), and flow cytometry for peripheral blood cluster of
      differentiation 4(+) (CD4(+)) and CD8(+) T-cells. RESULTS: There was no infection
      or death in the rats except one, which died in the first week. Compared to the
      control group, the RNAi group had fewer eukomonocytes infiltrated, which were
      only distributed around the graft. The ratio of CD4(+)/CD8(+) T-cells in the RNAi
      group was significantly lower than the normal one (P<0.05). There were many more
      positively stained chondrocytes and positively stained areas around the cells in
      the RNAi group, which were not found in the control group. CONCLUSION: The
      aggrecanase-1 and aggrecanase-2 RNAi for chondrocytes decreased the immunological
      rejection effect.

PMID- 24855368
TI  - Effects of extended-release niacin/laropiprant, simvastatin, and the combination
      on correlations between apolipoprotein B, LDL cholesterol, and non-HDL
      cholesterol in patients with dyslipidemia.
AB  - BACKGROUND: Statins modify correlations between apolipoprotein B (apoB) and low
      density lipoprotein cholesterol (LDL-C) and apoB and non-high-density lipoprotein
      cholesterol (non-HDL-C); however, it is not known whether niacin-based therapies
      have similar effects. OBJECTIVE: To evaluate the effects of extended-release
      niacin (ERN)/laropiprant (LRPT), simvastatin (SIMVA), and ERN/LRPT + SIMVA
      (pooled ERN/LRPT + SIMVA) on apoB:LDL-C and apoB:non-HDL-C correlations in
      dyslipidemic patients. METHODS: This post-hoc analysis of a 12-week study
      evaluated the apoB:LDL-C and apoB:non-HDL-C correlations in dyslipidemic patients
      randomized equally to double-blind ERN/LRPT 1 g/20 mg, SIMVA 10, 20, or 40 mg, or
      ERN/LRPT 1 g/20 mg + SIMVA (10, 20, or 40 mg) once daily for 4 weeks. At week 5,
      doses were doubled in all groups except SIMVA 40 mg (unchanged) and ERN/LRPT 1
      g/20 mg + SIMVA 40 mg (switched to ERN/LRPT 2 g/40 mg + SIMVA 40 mg). Simple
      linear regression analyses were used to calculate LDL-C and non-HDL-C levels
      corresponding to known apoB baseline values (ie, in untreated patients) and
      following treatment. RESULTS: The apoB:LDL-C and apoB:non-HDL-C correlations were
      higher and the predicted LDL-C and non-HDL-C levels for a known apoB value were
      considerably lower following treatment with ERN/LRPT, SIMVA and ERN/LRPT + SIMVA
      compared with untreated patients at baseline. CONCLUSION: Greater dissociation of
      apoB, LDL-C, and non-HDL-C targets occur following treatment with ERN/LRPT,
      SIMVA, and ERN/LRPT + SIMVA in patients with dyslipidemia. The achievement of
      more aggressive LDL-C and non-HDL-C goals in patients receiving lipid-modifying
      therapy may further reduce coronary risk by normalizing apoB-containing
      atherogenic lipoproteins.

PMID- 24855369
TI  - Pregnancy and fetal loss reported by methamphetamine-using women.
AB  - To better understand substance use disorder treatment needs of pregnant and
      parenting women who use methamphetamine (MA), this paper describes pregnancy
      histories and fetal losses for women who were treated for MA use (N = 153) with
      reference to a national sample, and describes their drug use, sexual risk
      behaviors, and mental health status. MA users reported an average of 4.6 total
      pregnancies and 2.1 fetal losses, whereas women in a general population survey
      reported 3.2 and 1.2, respectively. Higher numbers of pregnancies and fetal
      losses were correlated with specific substance abuse and mental health problems
      including early sexual abuse and cognitive problems. The combination of MA users'
      especially high numbers of pregnancies, fetal losses, and rates of risk behaviors
      suggest high social and health care costs for this population. Prenatal care may
      provide a vector through which women can be connected to risk reduction
      interventions and gender-responsive treatment services addressing substance use
      and mental health needs. 

PMID- 24855370
TI  - A longitudinal study on substance use and related problems in women in opioid
      maintenance treatment from pregnancy to four years after giving birth.
AB  - BACKGROUND: Women in opioid maintenance treatment (OMT) have a past characterized
      by drug abuse, which is a challenging start for parenthood. Studies of mothers in
      OMT are typically limited to pregnancy and early infancy. Knowledge about how
      they cope with substance use and related problems in the years following birth is
      therefore important. The aims of the study were to examine changes in mothers'
      substance use, psychological problems, and other challenges; from one to four
      years after their children were born, and describe kindergarten attendance and
      prevalence and type of child protective services involvement when the children
      were four years old. METHOD: A four-year prospective cohort study of mothers in
      OMT. The European severity index was used to map substance use and related
      problems during the third trimester of pregnancy, one and four years after birth.
      RESULTS: At the four-year follow-up, use of illegal substances remained low (4%)
      and use of legal substances (39%) was similar to the one-year follow-up. The
      proportion of women with psychological problems was significantly higher than at
      one-year follow-up (69 vs. 39%, P = 0.009). At age four, most children (89%)
      attended kindergarten, and the child protective services were following 73% of
      the families, mostly with voluntary measures. CONCLUSION: Mothers in OMT cope
      well with substance use over time, given access to sufficient support. The
      findings imply that a preventive governmental strategy with close support of
      mother and child, have a positive impact contributing to making OMT and
      motherhood more compatible.

PMID- 24855371
TI  - Breast Cancer Knowledge, Beliefs, and Screening Practices among Women Seeking
      Care at District Hospitals in Dar es Salaam, Tanzania.
AB  - BACKGROUND: Limited disease awareness among women may impact breast cancer stage
      at-diagnosis in Tanzania, reducing survival. This study assessed breast cancer
      knowledge, screening practices, and educational preferences among outpatients at
      Tanzanian government-supported hospitals. METHODS: A convenience sample of women
      was surveyed regarding (1) knowledge/beliefs of breast cancer etiology, risk
      factors, symptoms, treatment, (2) early detection knowledge/practice, and (3)
      educational preferences. RESULTS: Among 225 respondents, 98.2% knew of breast
      cancer; 22.2% knew someone affected by breast cancer. On average, 30% of risk
      factors and 51% of symptoms were identified. Most accepted one or more breast
      cancer myths. Among 126 aware of breast self-exam, 40% did not practice it; only
      0.9% underwent regular clinical breast examinations despite 68% being aware of
      the procedure. Among treatments, 87% recognized surgery, 70% radiation, and fewer
      systemic therapy. Preferred educational sources were group sessions,
      television/radio, and meetings with breast cancer survivors. CONCLUSIONS: This
      work reveals incomplete breast cancer awareness among Tanzanian women and
      promises to inform development of user-focused educational resources.

PMID- 24855372
TI  - Pertuzumab in Combination with Trastuzumab and Chemotherapy in the Treatment of
      HER2-Positive Metastatic Breast Cancer: Safety, Efficacy, and Progression Free
      Survival.
AB  - Tyrosine kinase inhibitors have revolutionized the oncology community and were
      pioneered by the use in HER2-targeted therapies. Improved outcomes were seen with
      the advent of trastuzumab, leading investigators to develop newer agents to
      target the HER2 pathway such as the novel monoclonal antibody pertuzumab. In this
      paper, we describe the attributes of pertuzumab including: mechanism of action,
      pharmacokinetics and metabolism, safety/cardiotoxicity, drug interactions,
      efficacy, and role in HER2-positive breast cancer management. Newly reviewed here
      versus previously published reviews on pertuzumab oriented therapy are data of
      pertuzumab monotherapy as it is used in combination with other anti-HER2 agents
      derived from preclinical research and ongoing clinical trials. MATERIALS AND
      METHODS: A computer based literature search was carried out using PubMed data
      reported at international meetings (ASCO) up to September 2013 were included.

PMID- 24855373
TI  - New Financial and Research Models for Pediatric Orphan Drug Development - Focus
      on the NCATS TRND Program.
AB  - While there are approximately 7,000 identified human diseases considered as
      "rare" based on population prevalence or incidence, the cumulative impact runs
      into the millions of patients globally. Although the genetic underpinnings of
      more than 2,000 rare diseases have been elucidated, there remains a paucity of
      therapeutic options, frequently due to lack of commercial interest. Development
      programs suffer high attrition within the so-called "Valley of Death," in which
      the risks of scientific failure are still too high to justify the increasing
      development costs. This problem is common to any drug development campaign, but
      it is particularly exacerbated in the rare diseases, many of which arise in
      childhood. To stimulate development of therapeutics for these otherwise
      underserved patient populations, a number of regulatory incentives and research
      initiatives have been established. Extended patent protections, expedited
      regulatory reviews for qualified drug sponsors, and clinical trial grant support
      aim to foster interest in completing development programs. To stimulate
      researchers to embark on rare disease drug development campaigns, earlier-stage
      preclinical research resources have been created, as well, such as the
      Therapeutics for Rare and Neglected Diseases (TRND) program at the U.S. National
      Institutes of Health (NIH). TRND is a unique NIH program created to support drug
      development through formation of public-private partnerships. These partnerships
      leverage the robust biopharmaceutical industry experience of the TRND staff
      scientists and the deep disease area expertise of the collaborating partners.
      Each project adopted into the TRND portfolio aims to satisfy two broad goals:
      developing a novel therapy for a rare or otherwise neglected disease, and
      exploring ways to accelerate the drug development process overall so that lessons
      learned can be disseminated to the wider community undertaking translational
      research. This article discusses common obstacles and opportunities for
      therapeutic development, and provides examples of the types of projects TRND has
      undertaken across a broad range of pediatric rare disorders.

PMID- 24855374
TI  - A framework for building research partnerships with first nations communities.
AB  - Solutions to complex health and environmental issues experienced by First Nations
      communities in Canada require the adoption of collaborative modes of research.
      The traditional "helicopter" approach to research applied in communities has led
      to disenchantment on the part of First Nations people and has impeded their
      willingness to participate in research. University researchers have tended to
      develop projects without community input and to adopt short term approaches to
      the entire process, perhaps a reflection of granting and publication cycles and
      other realities of academia. Researchers often enter communities, collect data
      without respect for local culture, and then exit, having had little or no
      community interaction or consideration of how results generated could benefit
      communities or lead to sustainable solutions. Community-based participatory
      research (CBPR) has emerged as an alternative to the helicopter approach and is
      promoted here as a method to research that will meet the objectives of both First
      Nations and research communities. CBPR is a collaborative approach that equitably
      involves all partners in the research process. Although the benefits of CBPR have
      been recognized by segments of the University research community, there exists a
      need for comprehensive changes in approaches to First Nations centered research,
      and additional guidance to researchers on how to establish respectful and
      productive partnerships with First Nations communities beyond a single funded
      research project. This article provides a brief overview of ethical guidelines
      developed for researchers planning studies involving Aboriginal people as well as
      the historical context and principles of CBPR. A framework for building research
      partnerships with First Nations communities that incorporates and builds upon the
      guidelines and principles of CBPR is then presented. The framework was based on
      10 years' experience working with First Nations communities in Saskatchewan. The
      framework for research partnership is composed of five phases. They are
      categorized as the pre-research, community consultation, community entry,
      research and research dissemination phases. These phases are cyclical, non-linear
      and interconnected. Elements of, and opportunities for, exploration, discussion,
      engagement, consultation, relationship building, partnership development,
      community involvement, and information sharing are key components of the five
      phases within the framework. The phases and elements within this proposed
      framework have been utilized to build and implement sustainable collaborative
      environmental health research projects with Saskatchewan First Nations
      communities. 

PMID- 24855375
TI  - A Moderate Zinc Deficiency Does Not Impair Gene Expression of PPARalpha,
      PPARgamma, and Mitochondrial Enoyl-CoA Delta Isomerase in the Liver of Growing
      Rats.
AB  - The aim of the study was to investigate the impact of a moderate zinc deficiency
      and a high intake of polyunsaturated fat on the mRNA expression of peroxisome
      proliferator-activated receptor alpha (PPARalpha), peroxisome-proliferator
      activated receptor gamma (PPARgamma), and mitochondrial Delta3Delta2-enoyl-CoA
      isomerase (ECI) in the liver. Weanling rats were assigned to five groups (eight
      animals each) and fed semi-synthetic, low-carbohydrate diets containing 7 or 50
      mg Zn/kg (low-Zn (LZ) or high-Zn (HZ)) and 22% cocoa butter (CB) or 22% safflower
      (SF) oil for four weeks. One group each was fed the LZ-CB, LZ-SF, or HZ-SF diet
      free choice, and one group each was fed the HZ-CB and HZ-SF diets in restricted
      amounts according to intake of the respective LZ diets. The LZ diets markedly
      lowered growth and zinc concentrations in plasma and femur. Hepatic mRNA levels
      of PPARalpha, PPARgamma, and ECI were not reduced by the moderate zinc
      deficiency. Overall, ECI-mRNA abundance was marginally higher in the SF-fed than
      in the CB-fed animals. 

PMID- 24855376
TI  - Kynurenic Acid levels in cerebrospinal fluid from patients with Alzheimer's
      disease or dementia with lewy bodies.
AB  - Kynurenic acid (KYNA) is implicated in cognitive functions. Altered
      concentrations of the compound are found in serum and cerebrospinal fluid (CSF)
      of patients with Alzheimer's disease (AD). Further studies to determine whether
      KYNA serves as a biomarker for cognitive decline and dementia progression are
      required. In this study, we measured CSF KYNA levels in AD patients (n = 19),
      patients with dementia with Lewy bodies (DLB) (n = 18), and healthy age-matched
      controls (Ctrls)) (n = 20) to further explore possible correlations between KYNA
      levels, cognitive decline, and well-established AD and inflammatory markers.
      Neither DLB patients nor AD patients showed significantly altered CSF KYNA levels
      compared to Ctrls. However, female AD patients displayed significantly higher
      KYNA levels compared to male AD patients, a gender difference not seen in the
      Ctrl or DLB group. Levels of KYNA significantly correlated with the AD-biomarker
      P-tau and the inflammation marker soluble intercellular adhesion molecule-1
      (sICAM-1) in the AD patient group. No associations between KYNA and cognitive
      functions were found. Our study shows that, although KYNA was not associated with
      cognitive decline in AD or DLB patients, it may be implicated in AD-related
      hyperphosphorylation of tau and inflammation. Further studies on larger patient
      cohorts are required to understand the potential role of KYNA in AD and DLB. 

PMID- 24855377
TI  - Transcriptional targeting of sphingosine-1-phosphate receptor S1P2 by
      epigallocatechin-3-gallate prevents sphingosine-1-phosphate-mediated signaling in
      macrophage-differentiated HL-60 promyelomonocytic leukemia cells.
AB  - BACKGROUND: Macrophage chemotaxis followed by blood-brain barrier
      transendothelial migration is believed to be associated with inflammation in the
      central nervous system. Antineuroinflammatory strategies have identified the
      dietary-derived epigallocatechin-3-gallate (EGCG) as an efficient agent to
      prevent neuroinflammation-associated neurodegenerative diseases by targeting
      proinflammatory mediator signaling. METHODS: Given that high levels of
      sphingosine kinase and its product, sphingosine-1-phosphate (S1P), are present in
      brain tumors, we used quantitative reverse-transcription polymerase chain
      reaction (qRT-PCR) and immunoblotting to test whether EGCG may impact on S1P
      receptor gene expression and prevent S1P response in undifferentiated and in
      terminally differentiated macrophages. RESULTS: Promyelomonocytic human leukemia
      (HL)-60 cells were differentiated into macrophages, and S1P triggered
      phosphorylation in extracellular signal-regulated kinase (ERK), c-Jun N-terminal
      kinase (JNK), and P38 mitogen-activated protein kinase (MAPK) intracellular
      signaling, as shown by Western blot analysis. Pretreatment of cells with EGCG
      prior to differentiation inhibited the response to S1P in all three pathways,
      while EGCG abrogated P38 MAPK phosphorylation when present only during
      differentiation. Terminally-differentiated macrophages were, however, insensitive
      to EGCG treatment. Using qRT-PCR, gene expression of the S1P receptors S1P1,
      S1P2, and S1P5 was predominantly induced in terminally-differentiated
      macrophages, while the S1P2 was decreased by EGCG treatment. CONCLUSION: Our data
      suggest that diet-derived EGCG achieves efficient effects as a preventive agent,
      targeting signaling pathways prior to cell terminal differentiation. Such
      properties could impact on cell chemotaxis through the blood-brain barrier and
      prevent cancer-related neuroinflammation.

PMID- 24855378
TI  - Renal malignant solitary fibrous tumor with single lymph node involvement: report
      of unusual metastasis and review of the literature.
AB  - Solitary fibrous tumors are rare mesenchymal spindle cell neoplasms that are
      usually found in the pleura. The kidneys are an uncommon site and only few cases
      of renal solitary fibrous tumor exhibit malignant behavior metastasizing to the
      liver, lung, and bone through the hematogenous pathway. PURPOSE: To describe the
      first case of lymph node metastasis from renal solitary fibrous tumor in order to
      increase the knowledge about the malignant behavior of these tumors. PATIENTS AND
      METHODS: A 19-year-old female patient had intermittent hematuria for several
      months without flank pain or other symptoms. A chest and abdomen CT scan was
      performed and showed a multi-lobed bulky solid mass of 170 * 98 * 120 mm in the
      left kidney. One day before the surgery, the left renal artery was catheterized
      and the kidney embolization was performed using a Haemostatic Absorbable Gelatin
      Sponge and polyvinyl alcohol. We then performed a radical nephrectomy with hilar,
      para-aortic, and inter-aortocaval lymphadenectomy. RESULTS: Estimated
      intraoperative blood loss was 200 mL and the operative time was 100 minutes. No
      postoperative complications occurred. The hospital stay was 7 days long. The
      histological examination was malignant solitary fibrous tumor of the kidney.
      Cancerous tissue showed cellular atypia, with an increased mitotic index (up to 7
      * 10 hpf). Immunohistochemical analysis showed positive results for CD34, BCL2,
      partial expression of HBME1, and occasionally of synaptophysin. Histological
      evaluation confirmed the presence of metastasis in one hilar node. The patient
      did not receive any other therapy. At 30-month follow-up, the patient was in good
      health and no local recurrence or metastases had occurred. CONCLUSION: This is
      the first case of lymph node metastasis from a renal solitary fibrous tumor
      showing unusual malignant behavior; this finding adds new information about the
      biology and progression of these tumors, which remain unclear.

PMID- 24855379
TI  - Quality of life assessment in advanced cancer patients treated at home, an
      inpatient unit, and a day care center.
AB  - AIM OF THE STUDY: To assess quality of life (QoL) in cancer patients treated at
      home, at an in-patient palliative care unit (PCU), and at a day care center
      (DCC). PATIENTS AND METHODS: QoL was assessed in advanced cancer patients at
      baseline and after 7 days of symptomatic treatment using the European
      Organization for Research and Treatment of Cancer Quality of Life Questionnaire
      Core 15-Palliative Care (EORTC QLQ-C15-PAL), the Edmonton Symptom Assessment
      System (ESAS), and the Karnofsky Performance Status (KPS) scale. RESULTS: A total
      of 129 patients completed the study, with 51 patients treated at home, 51
      patients treated at the PCU, and 27 patients at DCC. In the EORTC QLQ-C15-PAL,
      improvement in functional and symptom scales was observed except in physical
      functioning and fatigue levels; patients at DCC had a better physical
      functioning, global QoL, appetite, and fatigue levels. In the ESAS, improvement
      in all items was found except for drowsiness levels, which was stable in patients
      treated at DCC and deteriorated in home and PCU patients. Higher activity, better
      appetite and well-being, and less drowsiness were observed in patients treated at
      DCC. KPS was better in DCC patients compared to those treated at home and at the
      PCU; the latter group deteriorated. CONCLUSIONS: QoL improved in all patient
      groups, with better results in DCC patients and similar scores in those staying
      at home and at the PCU. Along with clinical assessment, baseline age, KPS,
      physical and emotional functioning may be considered when assigning patients to
      care at a DCC, PCU, or at home.

PMID- 24855380
TI  - Antitumor activity of sorafenib and imatinib in a patient with thymic carcinoma
      harboring c-KIT exon 13 missense mutation K642E.
AB  - We report the case of a man with an advanced nonkeratinizing squamous cell thymic
      carcinoma harboring c-KIT exon 13 missense mutation K642E. This aberration is
      rare and has never been described previously in patients with thymic cancers. It
      has been found in a small number of cases of gastrointestinal stromal tumor and
      also in several cases of acral and mucosal melanomas. Some of the patients with
      gastrointestinal stromal tumor or melanoma harboring this rare mutation have had
      a tumor response when treated with imatinib. In contrast, in our case, the
      mutation was associated with primary resistance to full doses of imatinib but, at
      the same time, it was not a cause of resistance to sorafenib. 

PMID- 24855382
TI  - Dressing-related trauma: clinical sequelae and resource utilization in a UK
      setting.
AB  - BACKGROUND: Dressings are the mainstay of wound care management; however,
      adherence of the dressing to the wound or periwound skin is common and can lead
      to dressing-related pain and trauma. Dressing-related trauma is recognized as a
      clinical and economic burden to patients and health care providers. This study
      was conducted to garner expert opinion on clinical sequelae and resource use
      associated with dressing-related trauma in a UK setting. METHODS: THIS WAS AN
      EXPLORATORY STUDY WITH TWO PHASES: qualitative pilot interviews with six wound
      care specialists to explore dressing-related trauma concepts, sequelae, and
      resource utilization; and online quantitative research with 30 wound care
      specialists to validate and quantify the concepts, sequelae, and resource
      utilization explored in the first phase of the study. Data were collected on mean
      health care professional time, material costs, pharmaceutical costs, and
      inpatient management per sequela occurrence until resolution. Data were analyzed
      to give total costs per sequela and concept occurrence. RESULTS: The results
      demonstrate that dressing-related trauma is a clinically relevant concept. The
      main types of dressing-related trauma concepts included skin reactions, adherence
      to the wound, skin stripping, maceration, drying, and plugging of the wound.
      These were the foundation for a number of clinical sequelae, including wound
      enlargement, increased exudate, bleeding, infection, pain, itching/excoriation,
      edema, dermatitis, inflammation, and anxiety. Mean total costs range from L56 to
      L175 for the complete onward management of each occurrence of the six main
      concepts. CONCLUSION: These results provide insight into the hidden costs of
      dressing-related trauma in a UK setting. This research successfully
      conceptualized dressing-related trauma, identified associated clinical sequelae,
      and quantified resource utilization associated with a typical occurrence of each
      trauma concept. Further research is warranted into dressing-related trauma and
      the associated costs.

PMID- 24855381
TI  - Staphylococcus aureus - antimicrobial resistance and the immunocompromised child.
AB  - Children with immunocompromising conditions represent a unique group for the
      acquisition of antimicrobial resistant infections due to their frequent
      encounters with the health care system, need for empiric antimicrobials, and
      immune dysfunction. These infections are further complicated in that there is a
      relative paucity of literature on the clinical features and management of
      Staphylococcus aureus infections in immunocompromised children. The available
      literature on the clinical features, antimicrobial susceptibility, and management
      of S. aureus infections in immunocompromised children is reviewed. S. aureus
      infections in children with human immunodeficiency virus (HIV) are associated
      with higher HIV viral loads and a greater degree of CD4 T-cell suppression. In
      addition, staphylococcal infections in children with HIV often exhibit a
      multidrug resistant phenotype. Children with cancer have a high rate of S. aureus
      bacteremia and associated complications. Increased tolerance to antiseptics among
      staphylococcal isolates from pediatric oncology patients is an emerging area of
      research. The incidence of S. aureus infections among pediatric solid organ
      transplant recipients varies considerably by the organ transplanted; in general
      however, staphylococci figure prominently among infections in the early
      posttransplant period. Staphylococcal infections are also prominent pathogens
      among children with a number of immunodeficiencies, notably chronic granulomatous
      disease. Significant gaps in knowledge exist regarding the epidemiology and
      management of S. aureus infection in these vulnerable children. 

PMID- 24855383
TI  - Effects of body mass index-related disorders on cognition: preliminary results.
AB  - BACKGROUND: Well-known risk factors for cognitive impairment are also associated
      with obesity. Research has highlighted genetic risk factors for obesity, yet the
      relationship of those risk factors with cognitive impairment is unknown. The
      objective of this study was to determine the associations between cognition,
      hypertension, diabetes, sleep-disordered breathing, and obesity. Genetic risk
      factors of obesity were also examined. METHODS: The sample consisted of 369
      nondemented individuals aged 50 years or older from four community cohorts.
      Primary outcome measures included auditory verbal memory, as measured by the Rey
      Auditory Verbal Learning Test, and executive functioning, as measured by the
      Color-Word Interference Test of the Delis-Kaplan Executive Function System
      battery. Apnea-hypopnea index indicators were determined during standard
      overnight polysomnography. Statistical analyses included Pearson correlations and
      linear regressions. RESULTS: Poor executive function and auditory verbal memory
      were linked to cardiovascular risk factors, but not directly to obesity. Genetic
      factors appeared to have a small but measureable association to obesity.
      CONCLUSION: A direct linkage between obesity and poor executive function and
      auditory verbal memory is difficult to discern, possibly because nonobese
      individuals may show cognitive impairment due to insulin resistance and the
      "metabolic syndrome".

PMID- 24855384
TI  - Autism spectrum disorders in children of parents with inflammatory bowel disease 
      a nationwide cohort study in Denmark.
AB  - PURPOSE: Inflammatory bowel disease (IBD) and autism spectrum disorders (ASD) may
      share genetic and environmental risk factors. We examined whether parental IBD is
      associated with an increased risk of ASD in offspring. METHODS: We conducted a
      registry-based nationwide cohort study including children born alive in Denmark
      from January 1, 1994 to December 31, 2009, with follow-up throughout 2010. IBD in
      parents and ASD in offspring were identified using inpatient and outpatient
      hospital diagnoses. We computed risk of ASD and crude and adjusted incidence rate
      ratios (aIRRs) with 95% confidence intervals (CI) using Cox proportional-hazards
      regression. We evaluated the risk of ASD according to maternal and paternal IBD,
      and separately for maternal and paternal Crohn's disease (CD) and ulcerative
      colitis (UC). Children with parents free of IBD were the comparison cohort.
      RESULTS: We identified 1,005,330 children during the study period. Among them,
      11,888 (1.2%) had a parent with IBD and 8,087 (0.8%) had a diagnosis of ASD
      during up to 17 years of follow-up. The 10-year risks of ASD were 0.7% among
      children of parents with IBD and 0.9% among children of parents without IBD. The
      aIRR for ASD among children with parental IBD was 0.8 (95% CI: 0.6-1.0), and
      results were similar regardless of parent of IBD origin or whether a parent had
      CD or UC. The estimates were similar for different ASD subtypes. CONCLUSION: We
      found no evidence of an increased risk of ASD among children born to parents with
      IBD.

PMID- 24855385
TI  - Clinical and economic aspects of sevelamer therapy in end-stage renal disease
      patients.
AB  - Phosphate control is still a great challenge in chronic kidney disease (CKD), and
      in spite of the great improvements in dialysis techniques, achievement of the
      goals for mineral metabolism control is still far from ideal. Aluminum hydroxide
      has been largely abandoned due to the high risk of aluminum toxicity, while the
      use of calcium-based phosphate binders may cause hypercalcemia, overzealous
      parathyroid suppression, and extraskeletal calcification. Sevelamer hydrochloride
      has been introduced as an efficient medication for phosphate control, with a
      lower risk of hypercalcemia and parathyroid suppression. Various clinical trials
      have compared the risk of vascular calcification between sevelamer and calcium
      salts with inconsistent results. In spite of these inconsistencies, the Kidney
      Disease Outcomes Quality Initiative (KDOQI) suggests non-calcium phosphate
      binders as the preferred phosphate binder in dialysis patients with severe
      vascular and/or other soft-tissue calcifications and in those with hypercalcemia
      or parathyroid hormone (PTH) <150 mg/dL. The Kidney Disease Improving Global
      Outcome (KDIGO) limits the use of non-calcium phosphate binders to patients with
      hypercalcemia. Regarding the effect on mortality, the results of clinical trials
      are again inconsistent. The other important aspect of using sevelamer is the
      issue of price, which is substantially higher than calcium-based phosphate
      binders. Reviewing the studies on economic aspects shows that sevelamer increases
      quality-adjusted life-years (QALY) and possibly life years, with a higher cost
      compared to calcium-based phosphate binders. In conclusion, sevelamer is a very
      useful drug for phosphate control, reduction of hypercalcemia, and lessening the
      risk of adynamic bone disease, with probable reduction in vascular calcification
      and possible reduction in mortality rate. It has a higher economic burden on
      health care systems compared to calcium-based phosphate binders. This may affect
      its extensive use according to guideline recommendations, and will be influenced
      by local health care budgets and the decision of health care strategists. 

PMID- 24855386
TI  - Pain assessment in animal models: do we need further studies?
AB  - In the last two decades, animal models have become important tools in
      understanding and treating pain, and in predicting analgesic efficacy. Although
      rodent models retain a dominant role in the study of pain mechanisms, large
      animal models may predict human biology and pharmacology in certain pain
      conditions more accurately. Taking into consideration the anatomical and
      physiological characteristics common to man and pigs (median body size, digestive
      apparatus, number, size, distribution and communication of vessels in dermal
      skin, epidermal-dermal junctions, the immunoreactivity of peptide nerve fibers,
      distribution of nociceptive and non-nociceptive fiber classes, and changes in
      axonal excitability), swines seem to provide the most suitable animal model for
      pain assessment. Locomotor function, clinical signs, and measurements
      (respiratory rate, heart rate, blood pressure, temperature, electromyography),
      behavior (bright/quiet, alert, responsive, depressed, unresponsive), plasma
      concentration of substance P and cortisol, vocalization, lameness, and axon
      reflex vasodilatation by laser Doppler imaging have been used to assess pain, but
      none of these evaluations have proved entirely satisfactory. It is necessary to
      identify new methods for evaluating pain in large animals (particularly pigs),
      because of their similarities to humans. This could lead to improved assessment
      of pain and improved analgesic treatment for both humans and laboratory animals. 

PMID- 24855387
TI  - Interstitial Cystitis - Elucidation of Psychophysiologic and Autonomic
      Characteristics (the ICEPAC Study): design and methods.
AB  - BACKGROUND AND PURPOSE: Interstitial cystitis/bladder pain syndrome (IC/BPS) is
      relatively common and associated with severe pain, yet effective treatment
      remains elusive. Research typically emphasized the bladder's role, but given the
      high presence of systemic comorbidities, the authors hypothesized a
      pathophysiologic nervous system role. This paper reports the methodology and
      approach to study the nervous system in women with IC/BPS. The study compares
      neurologic, urologic, gynecologic, autonomic, gastrointestinal, and psychological
      features of women with IC/BPS, their female relatives, women with myofascial
      pelvic pain (MPP), and healthy controls to elucidate the role of central and
      peripheral processing. METHODS AND RESULTS: In total, 228 women (76 IC/BPS, 76
      MPP, 38 family members, and 38 healthy controls) will be recruited. Subjects
      undergo detailed screening, structured neurologic examination of limbs and
      pelvis, tender point examination, autonomic testing, electrogastrography, and
      assessment of comorbid functional dysautonomias. Interpreters are blinded to
      subject classification. Psychological and stress response characteristics are
      examined with assessments of stress, trauma history, general psychological
      function, and stress response quantification. As of December 2012, data
      collection is completed for 25 healthy controls, 33 IC/BPS +/- MPP, eight MPP,
      and three family members. Recruitment rate is accelerating and strategies
      emphasize maintaining and encouraging investigator participation in study
      science, internet advertising, and presentations to pelvic pain support groups.
      CONCLUSION: The study represents a comprehensive, interdisciplinary approach to
      sampling autonomic and psychophysiologic characteristics of women with IC/BPS.
      Despite divergent opinions on study methodologies based on specialty experiences,
      the study has proven feasible to date and different perspectives have proved to
      be one of the greatest study strengths.

PMID- 24855388
TI  - A preliminary report on stem cell therapy for neuropathic pain in humans.
AB  - OBJECTIVE: Mesenchymal stem cells (MSCs) have been shown in animal models to
      attenuate chronic neuropathic pain. This preliminary study investigated if: i)
      injections of autologous MSCs can reduce human neuropathic pain and ii) evaluate
      the safety of the procedure. METHODS: Ten subjects with symptoms of neuropathic
      trigeminal pain underwent liposuction. The lipoaspirate was digested with
      collagenase and washed with saline three times. Following centrifugation, the
      stromal vascular fraction was resuspended in saline, and then transferred to
      syringes for local injections into the pain fields. Outcome measures at 6 months
      assessed reduction in: i) pain intensity measured by standard numerical rating
      scale from 0-10 and ii) daily dosage requirements of antineuropathic pain
      medication. RESULTS: Subjects were all female (mean age 55.3 years +/- standard
      deviation [SD] 14.67; range 27-80 years) with pain symptoms lasting from 4 months
      to 6 years and 5 months. Lipoaspirate collection ranged from 102-214 g with total
      cell numbers injected from 33 million to 162 million cells. Cell viability was
      62%-91%. There were no systemic or local tissue side effects from the stem cell
      therapy (n=41 oral and facial injection sites). Clinical pain outcomes showed
      that at 6 months, 5/9 subjects had reduced both pain intensity scores and use of
      antineuropathic medication. The mean pain score pre-treatment was 7.5 (SD 1.58)
      and at 6 months had decreased to 4.3 (SD 3.28), P=0.018, Wilcoxon signed-rank
      test. Antineuropathic pain medication use showed 5/9 subjects reduced their need
      for medication (gabapentin, P=0.053, Student's t-test). CONCLUSION: This
      preliminary open-labeled study showed autologous administration of stem cells for
      neuropathic trigeminal pain significantly reduced pain intensity at 6 months and
      is a safe and well tolerated intervention.

PMID- 24855390
TI  - Risk-benefit assessment of ivabradine in the treatment of chronic heart failure.
AB  - Heart rate is not only a major risk marker in heart failure but also a general
      risk marker. Within the last few years, it has been demonstrated that reduction
      of resting heart rate to <70 bpm is of significant benefit for patients with
      heart failure, especially those with impaired left ventricular systolic function.
      Ivabradine is the first innovative drug synthesized to reduce heart rate. It
      selectively and specifically inhibits the pacemaker I f ionic current, which
      reduces cardiac pacemaker activity. Therefore, the main effect of ivabradine
      therapy is a substantial lowering of heart rate. Ivabradine does not influence
      intracardiac conduction, contractility, or ventricular repolarization. According
      to the European Society of Cardiology guidelines, ivabradine should be considered
      in symptomatic patients (New York Heart Association functional class II-IV) with
      sinus rhythm, left ventricular ejection fraction <=35%, and heart rate >=70 bpm
      despite optimal treatment with a beta-blocker, angiotensin-converting enzyme
      inhibitor/angiotensin receptor blocker, and a mineralocorticoid receptor
      antagonist. As shown in numerous clinical studies, ivabradine improves clinical
      outcomes and quality of life and reduces the risk of death from heart failure or
      cardiovascular causes. Treatment with ivabradine is very well tolerated and safe,
      even at maximal recommended doses. 

PMID- 24855389
TI  - A systematic review of nonsurgical single-visit versus multiple-visit endodontic
      treatment.
AB  - Conventional endodontic treatment used to require multiple visits, but some
      clinicians have suggested that single-visit treatment is superior. Single-visit
      endodontic treatment and multiple-visit endodontic treatment both have their
      advantages and disadvantages. This paper is a literature review of the research
      on nonsurgical single-visit versus multiple-visit endodontic treatment. The
      PubMed database was searched using the keywords (endodontic treatment OR
      endodontic therapy OR root canal treatment OR root canal therapy) AND (single
      visit OR one-visit OR 1-visit). Review papers, case reports, data studies, and
      irrelevant reports were excluded, and 47 papers on clinical trials were reviewed.
      The studies generally had small sample sizes, and the endodontic procedures
      varied among the studies. Meta-analysis on the selected studies was performed,
      and the results showed that the postoperative complications of the single-visit
      and multiple-visit endodontic treatment were similar. Furthermore, neither single
      visit endodontic treatment nor multiple-visit treatment had superior results over
      the other in terms of healing or success rate. Results of limited studies on
      disinfection of the root canals using low-energy laser photodynamic therapy is
      inconclusive, and further studies are necessary to show whether laser should be
      used in endodontic treatment. This review also found that that neither single
      visit endodontic treatment nor multiple-visit treatment could guarantee the
      absence of postoperative pain. Since the study design of many studies displayed
      significant limitation and the materials and equipment used in endodontic
      treatment have dramatically changed in recent years, prospective randomized
      clinical trials are needed to further verify the postoperative pain and success
      rates of single-visit versus multiple-visit endodontic treatment. 

PMID- 24855392
TI  - Evaluation of fracture risk and potential drug holidays for postmenopausal women
      on long-term bisphosphonate therapy.
AB  - STUDY OBJECTIVE: To describe characteristics of postmenopausal women on long-term
      bisphosphonate therapy who fall into one of four fracture risk categories (low,
      mild, moderate, high), and to determine the prevalence of women eligible for a
      drug holiday. DESIGN: Retrospective electronic health record review. SETTING:
      Eight primary care clinics within a university-based health care system.
      PATIENTS: A total of 201 postmenopausal women of ages 55-89 years, with
      osteopenia or osteoporosis, prescribed bisphosphonate therapy for >4 years,
      between October 10, 2002 and September 9, 2012. MAIN RESULTS: The patients' mean
      age was 71.4 (+/-8.2) years; their mean body mass index was 25.3 (+/-5.6)
      kg/m(2); and 73.1% were white. Seventy-four out of 201 patients (36.8%) were low
      risk; 10/201 (5.0%) were mild-risk; 72/201 (35.8%) were moderate-risk; and 45/201
      (22.4%) were high-risk. Eighty-one women (40.3%) were eligible for a drug holiday
      or discontinuation. The estimated drug cost avoided per eligible patient was
      $574.80. Calcium and/or vitamin D supplementation was documented in 52.7% of
      women. CONCLUSION: More than one-third of postmenopausal women taking long-term
      bisphosphonate therapy had low fracture risk, and over 40% of our patients were
      eligible for a drug holiday or discontinuation. These data emphasize the need to
      accurately assess risk and benefit in patients treated with bisphosphonate
      therapy.

PMID- 24855391
TI  - Gut and mesenteric lymph node involvement in pediatric patients infected with
      human immunodeficiency virus.
AB  - BACKGROUND: The gastrointestinal tract is a primary target for human
      immunodeficiency virus (HIV). HIV infection causes a depletion of CD4+ T
      lymphocytes in gut-associated lymphoid tissue and affects gastrointestinal
      mucosal integrity and permeability. The gastrointestinal tract has also been
      suggested as the main reservoir of HIV despite highly active antiretroviral
      therapy (HAART). We performed a prospective case-control study to assess gut
      involvement in HIV-infected patients, either naive or on HAART, using noninvasive
      methods such as bowel ultrasound and fecal calprotectin. METHODS: Thirty HIV
      infected children and youth underwent the following tests: CD4+ T-cell count and
      HIV viral load, fecal calprotectin, and bowel ultrasound, with the latter
      evaluating bowel wall thickness and mesenteric lymph nodes. Fecal calprotectin
      and bowel ultrasound were also assessed in 30 healthy controls matched for age
      and sex. Fecal calprotectin was measured using a quantitative
      immunochromatographic point-of-care test, and concentrations ranging from 0 to
      200 MUg/g were considered to be normal reference values in children. RESULTS:
      Fecal calprotectin was normal in 29 HIV-infected patients and was not
      significantly different from controls (mean values 63.8+/-42.5 MUg/g and 68.3+/
      40.5 MUg/g, respectively; P=0.419), and did not correlate with HIV viral load,
      CD4+ T-cell absolute count and percentage, or HAART treatment. No significant
      changes were found on bowel ultrasound except for enlarged mesenteric lymph
      nodes, which were observed in seven HIV-infected patients (23.3%) and two
      controls (6.6%). This finding was significantly correlated with high HIV viral
      load (P=0.001) and low CD4+ T-cell percentage (P=0.004). CONCLUSION: HIV-infected
      children did not have significant biochemical or ultrasonographic signs of bowel
      inflammation. A few patients showed enlarged mesenteric lymph nodes, which
      correlated with uncontrolled HIV infection.

PMID- 24855393
TI  - Ulcerative colitis six years after colon cancer: only a coincidence?
AB  - The association between inflammatory bowel disease and colorectal cancer is well
      known. Ulcerative colitis is a risk factor for the development of colorectal
      cancer, and this risk increases with the activity and duration of bowel
      inflammation. Here we describe the case of a 52-year-old man who developed
      ulcerative colitis 6 years after the diagnosis and treatment of colon cancer.
      Although this could be a coincidence, there could be additional possibilities,
      like pre-existence of quiescent colitis, late effect of therapy, or maybe the
      existence of common pathogenetic factors contributing to the development of
      ulcerative colitis and colorectal cancer. 

PMID- 24855394
TI  - A case of thyroid storm with cardiac arrest.
AB  - A 23-year-old man became unconscious while jogging. He immediately received basic
      life support from a bystander and was transported to our hospital. On arrival,
      his spontaneous circulation had returned from a state of ventricular fibrillation
      and pulseless electrical activity. Following admission, hyperthyroidism led to a
      suspicion of thyroid storm, which was then diagnosed as a possible cause of the
      cardiac arrest. Although hyperthyroidism-induced cardiac arrest including
      ventricular fibrillation is rare, it should be considered when diagnosing the
      cause of treatable cardiac arrest. 

PMID- 24855395
TI  - Incidence and management of adverse events in patients with relapsed and/or
      refractory multiple myeloma receiving single-agent carfilzomib.
AB  - Carfilzomib, a selective proteasome inhibitor approved in the USA in 2012, is a
      single agent for relapsed and refractory multiple myeloma. Carfilzomib is
      administered as a 2-10-minute infusion on days 1, 2, 8, 9, 15, and 16 of a 28-day
      cycle at a starting dose of 20 mg/m(2) for cycle 1 and a target dose of 27
      mg/m(2) thereafter. In the pivotal Phase II study (PX-171-003-A1), carfilzomib
      20/27 mg/m(2) provided durable responses in a heavily pretreated population with
      relapsed and refractory multiple myeloma (n=266), with an overall response rate
      of 22.9% and a median duration of response of 7.8 months. In an integrated safety
      analysis of four Phase II studies, common adverse events (32.7%-55.5%) included
      fatigue, anemia, nausea, thrombocytopenia, dyspnea, and diarrhea. Grade 3/4
      adverse events were generally hematologic and included thrombocytopenia (23.4%),
      anemia (22.4%), and lymphopenia (18.1%). Serious adverse events included
      pneumonia (9.9%), acute renal failure (4.2%), pyrexia (3.4%), and congestive
      heart failure (3.4%). New or worsening peripheral neuropathy was infrequent
      (13.9% overall, 1.3% grade 3, no grade 4). This review discusses findings of the
      integrated safety analysis and provides practical experience from a single
      institution in managing treatment-related and disease-related adverse events.
      Individualized treatment with proactive management of side effects and
      complications allows patients with advanced multiple myeloma to remain on
      carfilzomib for extended periods. 

PMID- 24855396
TI  - Imaging biopsy composition at ACL reconstruction.
AB  - PURPOSE: Early-stage osteoarthritis (OA) includes glycosaminoglycan (GAG) loss
      and collagen disruption that cannot be seen on morphological magnetic resonance
      imaging (MRI). T1rho MRI is a measurement that probes the low-frequency rate of
      exchange between protons of free water and those from water associated with
      macromolecules in the cartilage's extracellular matrix. While it has been
      hypothesized that increased water mobility resulting from early osteoarthritic
      changes cause elevated T1rho MRI values, there remain several unknown mechanisms
      influencing T1rho measurements in cartilage. The purpose of this work was to
      relate histological and biochemical metrics directly measured from osteochondral
      biopsies and fluid specimens with quantitative MRI-detected changes of in vivo
      cartilage composition. PATIENTS AND METHODS: Six young patients were enrolled an
      average of 41 days after acute anterior cruciate ligament (ACL) rupture. Femoral
      trochlear groove osteochondral biopsies, serum, and synovial fluid were harvested
      during ACL reconstruction to complement a presurgery quantitative MRI study
      (T1rho, T2, delayed gadolinium-enhanced MRI of cartilage [dGEMRIC] relaxation
      times). A high-resolution MRI scan of the excised osteochondral biopsy was also
      collected. Analyses of in vivo T1rho images were compared with ex vivo T1rho
      imaging, GAG assays and histological GAG distribution in the osteochondral
      biopsies, and direct measures of bone and cartilage turnover markers and "OA
      marker" 3B3 in serum and synovial fluid samples. CONCLUSION: T1rho relaxation
      times in patients with a torn ACL were elevated from normal, indicating changes
      consistent with general fluid effusion after blunt joint trauma. Increased
      chondrogenic progenitor cell (CPC) production of chondroprotective lubricin may
      relate to cartilage surface disruption by blunt trauma and CPC amplification of
      joint inflammation. Disparity between ex vivo and matched in vivo MRI of
      trochlear cartilage suggests MRI signal differences that may be related to the
      synovial fluid environment. T1rho is emerging as a promising MRI biomarker to
      relate noninvasive measures of whole-joint condition and cartilage composition to
      direct measures of cartilage changes in the acute phase of joint injuries.

PMID- 24855397
TI  - The impact of balloon catheter dilation on frequency of sinus surgery in the
      United States.
AB  - PURPOSE: Endoscopic sinus surgery for patients with chronic rhinosinusitis (CRS)
      unresponsive to medical therapy has traditionally been performed under general
      anesthesia and in the operating room. Balloons for catheter dilation of paranasal
      sinuses were introduced in 2005, allowing sinus surgery to be safely performed
      either in the operating room or the office care setting, under local anesthesia.
      This change in care setting has raised concerns of overuse or expanded
      indications for sinus surgery. This study was thus designed to evaluate changes
      in surgical volumes in the United States, for the period 2006-2011, and to
      evaluate the impact of the sinus balloons on surgical practice. METHODS: The
      MarketScan((r)) Commercial Claims and Encounter Database was queried for the
      period 2006 to 2011 using CRS International Classification of Diseases, Ninth
      Revision codes (473.X) and sinus surgery US-based Common Procedural Terminology
      (CPT) codes (endoscopic sinus surgery: CPT codes 31254-31294 and 31299; balloon
      catheter dilation: CPT codes 31295-31297). MarketScan's projection methodology
      was applied to estimate the nationwide prevalence of CRS and the incidence of
      sinus surgery. Procedural case mix and total average payment per surgery were
      analyzed. RESULTS: From 2006 to 2011, the yearly prevalence of CRS and sinus
      surgery volume remained flat with ~430 patients with CRS per 100,000 in the
      employer-sponsored insured population, of which ~117/100,000 underwent surgery.
      In 2006, 2.69 paranasal sinuses (95% confidence interval [95% CI]: 2.65-2.71)
      were treated during each individual sinus surgery, with an additional 1.11 nasal
      procedures (95% CI: 1.08-1.13) performed concurrently. By 2011, the procedural
      case mix had expanded to 2.90 sinus (95% CI: 2.87-2.93) and 1.16 nasal procedures
      (95% CI: 1.14-1.85) per surgery. Payments increased from $7,011.06
      (alpha=$6,378.30; beta=3.1490) in 2006 to $9,090.11 (alpha=$8,350.20;
      beta=2.9535) in 2011, in line with US medical inflation. CONCLUSION: In the study
      population, approximately 1 in 3.7 patients diagnosed with CRS underwent sinus
      surgery. This ratio remained constant from 2006 to 2011. There was no evidence
      that the number of distinct sinus surgeries per 100,000 people increased despite
      the introduction and utilization of balloon catheter dilation tools that enabled
      migration of sinus surgery to the office.

PMID- 24855399
TI  - Back pain: the sole of presentation of sickle cell disease.
AB  - Diagnosing back pain in children and adolescents can be a challenge to health
      care providers. Although studies show that more than half of the cases of back
      pain in children are of non-organic cause, missing the right diagnosis could be
      detrimental. We present a case of lower back pain in a ten-year-old male whom we
      eventually diagnosed with hemoglobin SE mutation, which responded well to pain
      management. Hence, sickle cell disease with vaso-occlusive crisis should be
      incorporated into the list of differential diagnoses in children with back pain. 

PMID- 24855398
TI  - Erythropoiesis-stimulating agents for the treatment of chemotherapy-induced
      anemia: comparisons from real-world clinical experience.
AB  - BACKGROUND: The purpose of this paper is to report real-world data on the
      relative effectiveness of a biosimilar erythropoiesis-stimulating agent (ESA;
      Binocrit((r))), and other available ESAs for the treatment of chemotherapy
      induced anemia. METHODS: Data were collected retrospectively from single centers
      in Spain (n=284) and Germany (n=145). Hemoglobin outcomes, transfusion
      requirements, and serious drug-related adverse events were assessed for each ESA.
      RESULTS: Hemoglobin outcomes and transfusion requirements were generally similar
      in the different ESA treatment groups assessed. No serious drug-related adverse
      events were recorded in any of the treatment groups. CONCLUSION: These data
      confirm the real-world effectiveness and safety of a biosimilar ESA
      (Binocrit((r))) for the treatment of cancer patients with chemotherapy-induced
      anemia.

PMID- 24855400
TI  - A Case of Human Leukocyte Antigen (HLA) B27-Positive Intestinal Behcet's Disease
      with Crohn's Disease-Like Anal Fistulas.
AB  - A 49-year-old male was admitted to our hospital with complaints of perianal pain,
      bloody stool, and high-grade fever due to perianal abscess. Drainage was carried
      out; however, the patient's complaints worsened, and biopsy findings of
      colonoscopy showed ulcerative colitis-like lesions. The patient was diagnosed as
      having Behcet's disease with intestinal involvement, did not have HLA-B51, but
      did have HLA-B27. We describe a case of Behcet's disease with colitis, making a
      differential diagnosis of inflammatory bowel disease difficult. 

PMID- 24855401
TI  - Trajectories of Bone Remodeling Markers and Bone Mineral Density during Treatment
      with Strontium Ranelate in Postmenopausal Women Previously Treated with
      Bisphosphonates.
AB  - OBJECTIVE: To evaluate the responses of C-terminal telopeptide (CTX) and serum
      osteocalcin after the first 4 months of treatment with strontium ranelate (SR)
      and demonstrate their association with long-term bone density changes. SUBJECTS
      AND METHODS: A sample of 13 postmenopausal women with osteoporosis was analyzed
      (mean age 65 +/- 7.7 years), who were treated with SR for an average of 2.56 +/-
      0.86 years. All patients had undergone previous treatment with bisphosphonates
      for an average period of 4.88 +/- 2.27 years. Serum CTX and osteocalcin levels
      were determined before and after four months of treatment with SR. Bone mineral
      density in the lumbar spine and femoral neck were obtained before and after
      treatment with SR. RESULTS: We observed an average increase of 53.7% in the CTX
      levels, and 30.7% in the osteocalcin levels. The increase in bone markers was
      associated with a mean 4.8% increase in lumbar spine bone mineral density (BMD)
      from 0.820 to 0.860 g/cm(2) (T-score from -2.67 to -1.92; P = 0.001), after 2.5
      years of treatment with SR. CONCLUSION: These data suggest an anabolic effect of
      SR on postmenopausal women who were previously treated with long-term
      bisphosphonates.

PMID- 24855402
TI  - Newer dopaminergic agents cause minimal endocrine effects in idiopathic
      Parkinson's disease.
AB  - OBJECTIVE: We studied the prevalence of endocrine dysfunction in subjects with
      idiopathic Parkinson's disease (IPD) on newer dopaminergic agents (DA). DA are
      also used in endocrine hypersecretory states in small doses and we hypothesized
      that endocrine dysfunction was likely in IPD where DA were used in comparatively
      much higher dosage. PATIENTS AND METHODS: Twenty-five subjects with IPD,
      established on DA, were recruited to this cross-sectional study. We measured
      insulin-like growth factor-1, prolactin, luteinizing hormone, follicle
      stimulating hormone, thyroid function, oestradiol or testosterone and cortisol
      levels following a short synacthen test. RESULTS: We studied 18 males and 7
      females, whose median age was 72 years, and whose median time from diagnosis, and
      duration of treatment was 27 months (interquartile range 17-45 and 13-39 months,
      respectively). (1) Endocrine tests were normal in 19 of 25 subjects at
      recruitment. Minor abnormalities reverted to normal on repeat testing in three of
      six with initial abnormalities; two had persistent abnormalities and the third
      subject could not be further investigated. Therefore, 22 of 24 (92%) with IPD on
      DA therapy had normal endocrine profiles. (2) The cortisol response to ACTH was
      normal in 24 of 25 subjects (96%). (3) Eleven subjects (44%) had isolated PRL
      suppression. There were no differences between the suppressed PRL and "normal"
      PRL groups. However, a higher number of them were on non-ergoline-derived DA (83%
      vs 31%; P < 0.05). CONCLUSIONS: We have demonstrated that newer non-ergoline DA
      therapy caused only minimal endocrine perturbations in subjects with IPD. Their
      clinical significance can only be speculative currently. The cortisol response to
      ACTH was normal in almost all but a significant minority had suppressed prolactin
      levels.

PMID- 24855403
TI  - The Importance of Multidisciplinary Approach in Early Detection of BAP1 Tumor
      Predisposition Syndrome: Clinical Management and Risk Assessment.
AB  - Germline BAP1 (BRCA1-associated protein-1) mutations are involved into a novel
      specific cancer syndrome and strictly associated with a high cancer
      susceptibility. Recent data suggest that BAP1 has activity toward target
      substrates explaining why loss of BAP1 causes a pro-tumorigenic deregulation of
      gene expression. The recently published data reviewed raise the hypothesis that
      BAP1 regulates a common subset of substrates, which in turn causes a pro
      tumorigenic deregulation of gene expression, and alternatively suggest the role
      of BAP1 as tumorigenesis suppressor/promoter also by independent mechanisms. The
      clinical phenotype of BAP1 alterations includes MBAITs (melanocytic BAP1-mutated
      atypical intradermal tumors), uveal melanoma (UM), cutaneous melanoma (CM), renal
      cell carcinoma (RCC), mesothelioma (MM), and possibly several other tumors. In
      clinical practice, early diagnosis is crucial for curative resection of all these
      tumor types. The uniformed and unambiguous definition of MBAITs as
      clinical/pathological predictive markers could provide physicians means to
      identify patients who may carry germline BAP1 mutations and thus could be at high
      risk of developing CM, UM, MM, RCC, and possibly other tumors. As part of a novel
      multidisciplinary approach, physicians, pathologists, and clinicians involved
      into diagnostics should be aware of the histological features and the spectrum of
      tumors associated with BAP1 loss. Further clinical, epidemiological, and
      functional studies are required to fully explain the roles of BAP1 and its
      interaction partners in neoplasia, to define mechanisms behind shared and non
      shared clinical and pathological criteria. 

PMID- 24855405
TI  - Influenza vaccination in cancer patients undergoing systemic therapy.
AB  - BACKGROUND: Cancer patients often experience preventable infections, including
      influenza A and B. These infections can be a cause of significant morbidity and
      mortality. The increased risk of infection may be because of either cancer itself
      or treatment-induced immunosuppression.1 Influenza immunization has been shown to
      decrease the risk of influenza infection in patients with intact immunity.2 In
      cancer patients, active immunization has been shown to confer protective immunity
      against several infections at similar rates to healthy individuals, which has
      translated into decreased duration and severity of infection and potentially
      improved morbidity and mortality.3. OBJECTIVES: To assess the efficacy of
      influenza vaccination in stimulating immunological response in patients with
      cancer during chemotherapy compared to control groups.To assess the efficacy of
      influenza vaccination in preventing confirmed influenza and influenza-like
      illness and/or stimulating immunological response in children with cancer treated
      with chemotherapy, compared to placebo, no intervention, or different dosage
      schedules.To determine the adverse effects associated with influenza vaccination
      in patients with cancer. SEARCH METHODS: We searched MEDLINE/PubMed database for
      articles published from 1964 to 2013 using the search terms "cancer," "adult,"
      "influenza vaccination," and "chemotherapy." SELECTION CRITERIA: We included
      studies based on systematic sampling with defined clinical criteria irrespective
      of the vaccination status of cancer patients. Studies measure the serological
      response or clinical response to compare between the study group and the control
      group. Studies assessed the inactivated influenza vaccines and live attenuated
      influenza vaccine (LAIV) protective serological reaction and the clinical
      outcomes after vaccination. DATA COLLECTION AND ANALYSIS: Two independent authors
      assessed the methodological quality of included studies and extracted data. MAIN
      RESULTS: We included 16 studies (total number of participants = 1,076). None of
      the included studies reported clinical outcomes. All included studies reported on
      influenza immunity and adverse reaction on vaccination. We included 6 solid tumor
      studies and 10 hematological studies. In 12 studies, the serological response to
      influenza vaccine was compared in patients receiving chemotherapy (n = 425)
      versus those not receiving chemotherapy (n = 376). In three studies, the
      serological responses to influenza vaccination in patients receiving chemotherapy
      are compared to that in healthy adult. Measures used to assess the serological
      responses included a four-fold rise increase in antibody titer development of
      hemagglutination inhibition (HI) titer >40, and pre- and post-vaccination
      geometric mean titers (GMTs). Immune responses in patients receiving chemotherapy
      were consistently weaker (four-fold rise of 17-52%) than in those who had
      completed chemotherapy (50-83%) and healthy patients (67-100%). Concerning
      adverse effects, oncology patients received influenza vaccine, and the side
      effects described were mild local reactions and low-grade fever. No life
      threatening or persistent adverse effects were reported. AUTHORS' CONCLUSION:
      Patients with solid and some of hematological tumors are able to mount a
      serological response to influenza vaccine, but it remains unclear how much this
      response protects them from influenza infection or its complications. Meanwhile,
      influenza vaccine appears to be safe in these patients. While waiting results of
      randomized controlled trials to give us more details about the clinical benefits
      of the influenza vaccination, the clinicians should consider the currently proved
      benefits of influenza vaccination on management of the cancer patients undergoing
      systematic chemotherapy such as decrease in the duration and severity of the of
      the disease, and significant decrease in influenza-associated morbidity and
      mortality in these high-risk patients.3.

PMID- 24855404
TI  - What is the Best Treatment for a Cancer Patient with Thrombosis?
AB  - The relationship between venous thromboembolism and cancer has been known for
      many years, and there is solid scientific evidence addressing the adequate
      treatment of this condition in oncology patients. However, established
      prescribing habits, individual patient challenges, and uncertainty concerning
      treatment justifies poor adherence to published guidelines. This paper reviews
      venous thromboembolism treatment while focusing on vitamin K antagonists, low
      molecular-weight heparins, and novel oral anticoagulants, namely in terms of
      their efficacy and limitations. 

PMID- 24855406
TI  - Oncology nursing support for safe and effective use of eribulin in metastatic
      breast cancer.
AB  - Nurse practitioners play important roles in breast cancer prevention, early
      detection, therapeutic efficacy, and surveillance. Assessment of a patient's
      health status is part of the nine nurse practitioner core competencies updated in
      2012 by the National Organization of Nurse Practitioner Faculties. Although
      adverse events are common in treatment for metastatic breast cancer (MBC),
      proactive management strategies can limit the number and/or severity of adverse
      events. Additionally, knowledge of common metastatic sites and clinical
      signs/symptoms of recurrence provides one of the first-line strategies for
      successful treatment. We review five case studies of women with MBC who were
      managed successfully with eribulin mesylate in late lines of therapy after at
      least two chemotherapeutic regimens for advanced breast cancer that included both
      an anthracycline and a taxane in either the adjuvant or metastatic setting. 

PMID- 24855407
TI  - Efficacy and side effects of natalizumab therapy in patients with multiple
      sclerosis.
AB  - Natalizumab (Nat) is a humanized monoclonal antibody used for the treatment of
      relapsing multiple sclerosis (MS). Nat inhibits lymphocyte migration via the
      blood brain barrier (BBB) by blockage of an integrin adhesion molecule, very late
      antigen 4. During the phase III clinical trials, it was shown that Nat reduces
      disease activity and prevents disability progression. In addition, several
      smaller studies indicate a positive influence of Nat on cognition, depression,
      fatigue, and quality of life (Qol). Therapeutic efficacy has to be weighed
      against the risk of developing potentially fatal progressive multifocal
      leukoencephalopathy (PML), an opportunistic infection by JC-virus (JCV) with an
      incidence of 3.4/1000 (95% CI 3.08-3.74) in Nat treated MS patients. In this
      review article, we will review data on the presumed mechanism of Nat action,
      clinical and paraclinical efficacy parameters, and adverse drug reactions with a
      special focus on PML. 

PMID- 24855408
TI  - Patients' perception on the nutritional therapy for diabetic nephropathy.
AB  - Low protein diet (LPD) plays an important role in preventing the progression of
      diabetic nephropathy. However, it is a great burden to the patients. In this
      paper, we have studied the quality of life (QOL) in such patients. The study
      subjects were 59 patients (male 38, female 21) with type 2 diabetes. The patients
      were classified into tertiles based on their protein intake (g/kg BW). Scores
      from the diet-related QOL questionnaire were summarized by principal component
      analysis into four components; mental health, less burden, satisfaction and
      merit, and less social restriction. Higher protein intake was associated with
      less burden and less social restriction. In multiple regression analysis, the
      significant predictors for the "less burden" component were higher protein
      intake/BW and estimated glomerular filtration rate (eGFR). In summary, registered
      dietitians and clinicians must keep in mind that LPD is a serious burden to the
      patients and efforts must be made to minimize their burden in order to avoid
      discontinuation. 

PMID- 24855410
TI  - EPIQ Review.
AB  - BACKGROUND: A checklist that promotes compliance with aseptic technique during
      line insertion is a component of many care bundles aimed at reducing nosocomial
      infections among intensive care unit patients. OBJECTIVE: To determine whether
      the use of bundled interventions that include a checklist during central-line
      insertions reduces catheter-related bloodstream infections in intensive care unit
      patients. METHODS: A literature review was performed using methodology adapted
      from the American Heart Association's International Liaison Committee on
      Resuscitation. RESULTS: Seventeen cohort studies were included. Thirteen studies
      were supportive of the intervention, while four were neutral. Infection rates
      ranged from 1.6 to 10.8 per 1000 central-line days in control groups, and from
      0.0 to 3.8 per 1000 central-line days in the intervention groups. CONCLUSION:
      There is fair evidence to recommend the use of care bundles that include a
      checklist during central-line insertion in intensive care unit patients to reduce
      the incidence of catheter-related bloodstream infections.

PMID- 24855411
TI  - Case 1: An eight-year-old girl with short stature.

PMID- 24855412
TI  - Case 2: A nine-year-old girl with prolonged fever and headache.

PMID- 24855409
TI  - Impact of a medical student alcohol intervention workshop using recovering
      alcoholics as simulated patients.
AB  - BACKGROUND: Alcohol screening and brief intervention (SBI) reduces drinking among
      at-risk drinkers. Lack of training and negative attitudes represents a barrier to
      SBI performance. This study evaluates the impact of a medical student workshop
      using recovering alcoholics in simulated patient interviews to teach SBI skills.
      METHODS: Third-year students (n=94) were surveyed before and after a 3-hour
      alcohol SBI workshop regarding their perceived importance and confidence in
      performing eleven SBI behaviors. Students were also asked to list factors
      increasing and decreasing motivation to conduct SBI. Students completing off
      campus rotations (n=71) served as controls, completing surveys during the same
      time period but without attending the workshop. RESULTS: Analysis of variance
      found a significant interaction effect between the students participating in the
      workshop and control students on both importance scores [F(2,174)=3.34] and
      confidence scores [F(2,174)=9.13], indicating higher scores for the workshop
      students at the follow-up time periods. Commonly listed motivators for performing
      SBI included clinical experience with alcohol misuse and the impact of alcohol on
      health and relationships. High relapse rates and patient reactions to questions
      about alcohol use decreased the motivation to perform SBI. CONCLUSION: SBI
      workshops that include recovering alcoholics as simulated patients can produce
      long-term improvements in students' perceived importance and confidence in
      performing SBI.

PMID- 24855413
TI  - Procedural skills in paediatric residency: Re-evaluating the competencies.
AB  - BACKGROUND: The Royal College of Physicians and Surgeons of Canada (RCPSC) sets
      objectives for residency training, including many skills that may not be commonly
      performed in practice. OBJECTIVE: To describe attitudes of residents enrolled in
      Canadian paediatric residency programs toward procedural skills training,
      including perception of importance and perceived proficiency of the RCPSC
      required procedures. METHODS: An anonymous electronic survey was distributed to
      all senior residents enrolled in Canadian paediatric residencies, using a five
      point Likert scale to address procedural importance and corresponding
      proficiency. Data were analyzed using descriptive statistics, with Pearson
      correlation coefficients used to describe relationships among variables. RESULTS:
      A total of 68 residents responded. Fifteen skills had a mean importance >=4 (very
      or extremely important) and five skills had a mean rating <3 (somewhat or not
      important). Residents believed they were extremely or very proficient (mean
      rating >=4) for three skills (bag-mask ventilation, lumbar puncture and chest x
      ray interpretation). They reported 23 procedures for which they felt somewhat to
      not proficient (mean <3). The correlation between importance and proficiency was
      high (Pearson's correlation coefficient = 0.87). However, proficiency was
      significantly lower than importance (P<0.05) for the majority of procedures
      (88%). The largest gaps between importance and proficiency were observed for
      chest tube insertion, gathering evidence of child maltreatment, defibrillation
      and intraosseous insertion. CONCLUSION: Many, but not all, RCPSC-required
      procedures are believed to be important. Residents do not believe that they are
      adequately proficient in many of these procedures. Skills with the greatest gap
      between importance and proficiency may be targets for curricular interventions.

PMID- 24855414
TI  - Trends in the prevalence of cerebral palsy among very preterm infants (<31 weeks'
      gestational age).
AB  - BACKGROUND: The birth prevalence of cerebral palsy varies over time among very
      preterm infants, and the reasons are poorly understood. OBJECTIVE: To describe
      the variation in the prevalence of cerebral palsy among very preterm infants over
      time, and to relate these differences to other maternal or neonatal factors.
      METHODS: A population-based cohort of very preterm infants was evaluated over a
      20-year period (1988 to 2007) divided into four equal epochs. RESULTS: The
      prevalence of cerebral palsy peaked in the third epoch (1998 to 2002) while
      mortality rate peaked in the second epoch (1993 to 1997). Maternal anemia,
      tocolytic use and neonatal need for home oxygen were highest in the third epoch.
      CONCLUSIONS: Lower mortality rates did not correlate well with the prevalence of
      cerebral palsy. Maternal risk factors, anemia and tocolytic use, and the newborn
      need for home oxygen were highest during the same epoch as the peak prevalence of
      cerebral palsy.

PMID- 24855415
TI  - Paediatric pain management practice and policies across Alberta emergency
      departments.
AB  - BACKGROUND: Many children requiring acute care receive suboptimal analgesia.
      OBJECTIVES: To describe paediatric pain management practices and policies in
      emergency departments (EDs) in Alberta. METHODS: A descriptive survey was
      distributed to each of the EDs in Alberta. RESULTS: A response rate of 67% (72 of
      108) was obtained. Seventy-one percent (42 of 59) of EDs reported the use of a
      pain tool, 29.3% (17 of 58) reported mandatory pain documentation and 16.7% (10
      of 60) had nurse-initiated pain protocols. Topical anesthetics were reported to
      be used for intravenous line insertion by 70.4% of respondents (38 of 54) and for
      lumbar puncture (LP) by 30.8% (12 of 39). According to respondents, infiltrated
      anesthetic was used for LP by 69.2% (27 of 39) of respondents, and oral sucrose
      was used infrequently for urinary catheterization (one of 46 [2.2%]), intravenous
      line insertion (zero of 54 [0%]) and LP (one of 39 [2.6%]). CONCLUSIONS: Few
      Alberta EDs use policies and protocols to manage paediatric pain. Noninvasive
      methods to limit procedural pain are underutilized. Canadian paediatricians must
      advocate for improved analgesia to narrow this knowledge-to-practice gap.

PMID- 24855417
TI  - Corrigendum.

PMID- 24855416
TI  - From office tools to community supports: The need for infrastructure to address
      the social determinants of health in paediatric practice.
AB  - Previous research has highlighted the importance of addressing the social
      determinants of health to improve child health outcomes. However, significant
      barriers exist that limit the paediatrician's ability to properly address these
      issues. Barriers include a lack of clinical time, resources, training and
      education with regard to the social determinants of health; awareness of
      community resources; and case-management capacity. General practice
      recommendations to help the health care provider link patients to the community
      are insufficient. The objective of the current article was to present options for
      improving the link between the office and the community, using screening
      questions incorporating physician-based tools that link community resources.
      Simple interventions, such as routine referral to early-year centres and selected
      referral to public health home-visiting programs, may help to address populations
      with the greatest needs. 

PMID- 24855418
TI  - Prevention and management of neonatal herpes simplex virus infections.
AB  - Human herpes simplex virus (HSV) infection in neonates can result in devastating
      outcomes, including mortality and significant morbidity. All infants are
      potentially at risk for neonatal HSV infection. This position statement reviews
      epidemiology, transmission and risk factors, with a focus on intrapartum
      infection. It considers diagnosis and prognosis according to infection category,
      along with testing modalities and limitations. Recommendations for managing
      newborns known to have been exposed intrapartum to HSV are based on expert
      opinion because a randomized trial to compare management options is not feasible.
      Guidance is provided for the empirical management of infants with suspected
      clinical sepsis, including those who do not respond to antibacterial therapy. The
      present statement replaces a 2006 position statement by the Canadian Paediatric
      Society. 

PMID- 24855419
TI  - Red blood cell transfusion in newborn infants.
AB  - Red blood cell transfusion is an important and frequent component of neonatal
      intensive care. The present position statement addresses the methods and
      indications for red blood cell transfusion of the newborn, based on a review of
      the current literature. The most frequent indications for blood transfusion in
      the newborn are the acute treatment of perinatal hemorrhagic shock and the
      recurrent correction of anemia of prematurity. Perinatal hemorrhagic shock
      requires immediate treatment with large quantities of red blood cells; the
      effects of massive transfusion on other blood components must be considered. Some
      guidelines are now available from clinical trials investigating transfusion in
      anemia of prematurity; however, considerable uncertainty remains. There is weak
      evidence that cognitive impairment may be more severe at follow-up in extremely
      low birth weight infants transfused at lower hemoglobin thresholds; therefore,
      these thresholds should be maintained by transfusion therapy. Although the risks
      of transfusion have declined considerably in recent years, they can be minimized
      further by carefully restricting neonatal blood sampling. 

PMID- 24855420
TI  - Use of bundled interventions, including a checklist to promote compliance with
      aseptic technique, to reduce catheter-related bloodstream infections in the
      intensive care unit.
AB  - BACKGROUND: A checklist that promotes compliance with aseptic technique during
      line insertion is a component of many care bundles aimed at reducing nosocomial
      infections among intensive care unit patients. OBJECTIVE: To determine whether
      the use of bundled interventions that include a checklist during central-line
      insertions reduces catheter-related bloodstream infections in intensive care unit
      patients. METHODS: A literature review was performed using methodology adapted
      from the American Heart Association's International Liaison Committee on
      Resuscitation. RESULTS: Seventeen cohort studies were included. Thirteen studies
      were supportive of the intervention, while four were neutral. Infection rates
      ranged from 1.6 to 10.8 per 1000 central-line days in control groups, and from
      0.0 to 3.8 per 1000 central-line days in the intervention groups. CONCLUSION:
      There is fair evidence to recommend the use of care bundles that include a
      checklist during central-line insertion in intensive care unit patients to reduce
      the incidence of catheter-related bloodstream infections.

PMID- 24855421
TI  - Case 1: Recurrent abdominal pain in an adolescent girl.

PMID- 24855422
TI  - Case 2: Generalized swelling in a child with newly diagnosed diabetes mellitus.

PMID- 24855423
TI  - Parental perceptions regarding lifestyle interventions for obese children and
      adolescents with nonalcoholic fatty liver disease.
AB  - BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) affects 30% of obese
      children globally. The main treatment for NAFLD is to promote gradual weight loss
      through lifestyle modification. Very little is known regarding parental
      perspectives about the barriers and facilitators that influence the ability to
      promote healthy lifestyle behaviours in children with NAFLD. OBJECTIVES: To
      explore and describe parental perspectives regarding barriers to and facilitators
      of implementing lifestyle modification in children with NAFLD. METHODS: A mixed
      methods approach, including qualitative methodology (focus groups) and validated
      questionnaires (Lifestyle Behaviour Checklist), was used to assess parental
      perceptions regarding barriers to and facilitators of lifestyle change in parents
      of children with healthy body weights (control parents) and in parents of
      children with NAFLD (NAFLD parents). RESULTS: NAFLD parents identified more
      problem behaviours related to food portion size and time spent in nonsedentary
      physical activity, and lower parental self-efficacy than parents of controls
      (P<0.05). Major barriers to lifestyle change cited by NAFLD parents were lack of
      time, self-motivation and role modelling of healthy lifestyle behaviours. In
      contrast, control parents used a variety of strategies to elicit healthy
      lifestyle behaviours in their children including positive role modelling, and
      inclusion of the child in food preparation and meal purchasing decisions, and
      perceived few barriers to promoting healthy lifestyles. Internet sources were the
      main form of nutrition information used by parents. CONCLUSIONS: Lifestyle
      modification strategies focused on promoting increased parental self-efficacy and
      parental motivation to promote healthy lifestyle behaviour are important
      components in the treatment of obese children with NAFLD.

PMID- 24855424
TI  - Childhood immunization rates in Canada are too low: UNICEF.

PMID- 24855425
TI  - Kawasaki disease: High index of suspicion needed in a febrile child.

PMID- 24855426
TI  - Developmental milestones among Aboriginal children in Canada.
AB  - BACKGROUND: Windows of achievement provide age ranges for the attainment of early
      developmental skills. Group-specific research is warranted given that development
      may be influenced by social or cultural factors. OBJECTIVES: To examine
      developmental milestones for Inuit, Metis and off-reserve First Nation children
      in Canada, based on developmental domains collected from the 2006 Aboriginal
      Children's Survey. Sociodemographic and health predictors of risk for
      developmental delay were also examined. RESULTS: The ranges in which children
      achieve certain developmental milestones are presented. Gross motor and self-help
      skills were found to be achieved earlier (across the three Aboriginal groups),
      whereas language skills were achieved slightly later than in Canadian children in
      general. Furthermore, health factors (eg, low birth weight, chronic health
      conditions) were associated with late achievement of developmental outcomes even
      when sociodemographic characteristics were considered. CONCLUSIONS: Findings
      suggest that the timing of milestone achievement may differ for Aboriginal
      children, highlighting the importance of establishing culturally specific norms
      and standards rather than relying on those derived from general populations. This
      information may be useful for practitioners and parents interested in identifying
      the age ranges for development, as well as age ranges indicating potential for
      developmental risk and opportunities for early intervention among Aboriginal
      children.

PMID- 24855427
TI  - A collaborative outreach clinic for pregnant youth and adolescent mothers:
      Description of a pilot clinic and its patients.
AB  - OBJECTIVE: To describe the pregnant youth and adolescent parents seen at an
      adolescent health outreach clinic in an urban community setting during a two-year
      pilot project. METHODS: A retrospective chart review of all adolescents who
      presented at the monthly half-day clinics from January 2008 through January 2010
      (n=36) was performed. Measures extracted from charts included demographic
      information, reason for referral, social history, mental health history and
      outcome of assessment. RESULTS: All participants were female (mean age 17 years).
      Forty-two percent were pregnant at initial assessment, while the remainder had
      one or two children, or a recent pregnancy loss. Sixty-one percent had no primary
      care physician. The primary reason for referral was mental health concerns, most
      commonly depression. Almost one-half of patients relied on social assistance and
      almost one-third were living in shelters. At the time of first visit, 42% of
      patients were not attending school; the highest level of school completed for
      most patients was grade 8. The majority had a history of mental health issues and
      previous drug and/or alcohol use. CONCLUSIONS: Adolescents presenting to the
      clinic had a history of disadvantage in terms of income, educational attainment,
      living arrangements and mental health background, and are in need of various
      health services including primary care practitioners. These findings will help to
      inform future program development for these vulnerable youth, and have
      implications for practitioners caring for this population.

PMID- 24855428
TI  - Do obese children experience more severe fractures than nonobese children? A
      cross-sectional study from a paediatric emergency department.
AB  - OBJECTIVES: To determine whether there is an association between childhood
      obesity and severe extremity fractures. Associations between obesity and
      complications related to the fracture and/or fracture management were also
      examined. METHODS: The present study was a retrospective, cross-sectional study
      conducted at a tertiary care children's emergency department. Eligible cases for
      review were children (two to 17 years of age) with an extremity fracture. Severe
      extremity fractures were defined as those requiring manipulation under
      anesthesia, open operative repair and/or admission to hospital. The primary
      outcome was the proportion of severe extremity fractures and the secondary
      outcome was the proportion of complications. RESULTS: A total of 1340 charts of
      children who presented with extremity fracture from January 2008 to December 2010
      were reviewed. The mean (+/- SD) age of the study population was 9.1+/-4.0 years
      and 62.1% were male. Overall, 19.9% (95% CI 17.8% to 22.0%) were obese and 39.6%
      (95% CI 36.7% to 39.1%) sustained a severe extremity fracture. The OR of severe
      extremity fractures among obese versus nonobese children was 1.00 (95% CI 0.76 to
      1.32), adjusted for age, sex and mechanism of injury. In addition, the OR of
      experiencing complications among obese relative to nonobese children was 1.12
      (95% CI 0.68 to 1.85). CONCLUSIONS: The results of the present study demonstrated
      that in children with extremity fractures, obese children were not at increased
      risk for sustaining more severe extremity fractures or subsequent complications
      compared with nonobese children.

PMID- 24855429
TI  - Cardiovascular risk factors and health behaviours in elementary school-age
      Inuvialuit and Gwich'in children.
AB  - OBJECTIVES: To determine cardiovascular risk factors and health behaviours in
      Aboriginal children from the Beaufort-Delta region (Northwest Territories).
      METHODS: A total of 91 elementary school-age children underwent a cross-sectional
      assessment of body mass index, waist circumference, blood pressure and aerobic
      fitness. Healthy living knowledge and behaviours, including frequency of self
      reported physical activity (PA) and dietary intake, were also evaluated. RESULTS:
      A total of 49.5% of children were obese/overweight and 31.9% had elevated blood
      pressure. The percentages having one, two or three cardiovascular risk factor(s)
      were 64.4%, 42.2% and 15.6%, respectively, with no significant difference between
      boys and girls. Overall, the students obtained higher mean scores in the areas of
      healthy PA, body image, self-esteem and nutritious beverage knowledge (89%, 85%,
      79% and 71% of the maximum scores, respectively). The lowest scores were in
      nutritious food consumption and healthy PA frequency (46% and 56% of the maximum
      scores, respectively). On average, children consumed 2.7 L of sugar-sweetened
      beverages weekly and <2 servings of fruits or vegetables daily. Children spent
      approximately 2 h per day watching television, playing games or using a computer.
      CONCLUSION: There is an urgent need for community-based approaches to address the
      high rates of obesity and related cardiovascular risk factors among these
      Aboriginal children. Given the disconnect between healthy living knowledge and
      behaviour, it is important that future treatment programs address other barriers
      faced by Aboriginal populations living in rural and remote regions, including the
      high cost and limited access to high-quality nutritious foods and beverages, and
      limited access to indoor recreational programs over the long winter season.

PMID- 24855430
TI  - Antimicrobial stewardship in daily practice: Managing an important resource.
AB  - Antimicrobial stewardship is a recent concept that embodies the practical,
      judicious use of antimicrobials to decrease adverse outcomes from antimicrobials
      while optimizing the treatment of bacterial infections to reduce the emergence of
      resistant pathogens. The objectives of the present statement are to illustrate
      the principles of antimicrobial stewardship and to offer practical examples of
      how to make antimicrobial stewardship part of everyday hospital and outpatient
      practice. Vital components of antimicrobial stewardship include appropriate
      testing to diagnose whether infections are viral or bacterial, and using clinical
      follow-up rather than antibiotics in cases in which the child is not very ill and
      uncertainty exists. Other specific, important actions include questioning whether
      positive urine cultures are contaminated when there is no evidence of pyuria or
      inflammatory changes, and obtaining a chest radiograph to support a diagnosis of
      bacterial pneumonia. Optimizing the choice and dosage of antimicrobials also
      reduces the probability of clinical failures and subsequent courses of
      antimicrobials. A list of common clinical scenarios to promote stew-ardship is
      included. 

PMID- 24855431
TI  - Preventing and treating infections in children with asplenia or hyposplenia.
AB  - Children with asplenia or hyposplenia are at risk of developing overwhelming
      sepsis. Health care providers caring for children with asplenia should ensure the
      best outcomes by using preventive strategies that focus on parent and patient
      education, immunization, antibiotic prophylaxis and aggressive management of
      suspected infection. The present position statement offers current guidance on
      each of these issues and replaces a previous CPS statement, 'Prevention and
      therapy of bacterial infections for children with asplenia or hyposplenia',
      published in 1999. 

PMID- 24855433
TI  - First record of the genus Echthronomas Forster, 1869 (Hymenoptera, Ichneumonidae,
      Campopleginae) for the fauna of Ukraine.
AB  - The genus Echthronomas Forster, 1869 and two species, Echthronomasfacialis
      (Thomson, 1887) and Echthronomasquadrinotata (Thomson, 1887), are recorded for
      the fauna of Ukraine for the first time. Descriptions and photographs of species
      are provided. 

PMID- 24855432
TI  - Parental perceptions regarding lifestyle interventions for obese children and
      adolescents with nonalcoholic fatty liver disease.
AB  - BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) affects 30% of obese
      children globally. The main treatment for NAFLD is to promote gradual weight loss
      through lifestyle modification. Very little is known regarding parental
      perspectives about the barriers and facilitators that influence the ability to
      promote healthy lifestyle behaviours in children with NAFLD. OBJECTIVES: To
      explore and describe parental perspectives regarding barriers to and facilitators
      of implementing lifestyle modification in children with NAFLD. METHODS: A mixed
      methods approach, including qualitative methodology (focus groups) and validated
      questionnaires (Lifestyle Behaviour Checklist), was used to assess parental
      perceptions regarding barriers to and facilitators of lifestyle change in parents
      of children with healthy body weights (control parents) and in parents of
      children with NAFLD (NAFLD parents). RESULTS: NAFLD parents identified more
      problem behaviours related to food portion size and time spent in nonsedentary
      physical activity, and lower parental self-efficacy than parents of controls
      (P<0.05). Major barriers to lifestyle change cited by NAFLD parents were lack of
      time, self-motivation and role modelling of healthy lifestyle behaviours. In
      contrast, control parents used a variety of strategies to elicit healthy
      lifestyle behaviours in their children including positive role modelling, and
      inclusion of the child in food preparation and meal purchasing decisions, and
      perceived few barriers to promoting healthy lifestyles. Internet sources were the
      main form of nutrition information used by parents. CONCLUSIONS: Lifestyle
      modification strategies focused on promoting increased parental self-efficacy and
      parental motivation to promote healthy lifestyle behaviour are important
      components in the treatment of obese children with NAFLD.

PMID- 24855435
TI  - New records in vascular plants alien to Kyrgyzstan.
AB  - A series of brief notes on distribution of vascular plants alien to Kyrgyzstan is
      presented. A further expansion of Anthemisruthenica (Asteraceae),
      Crambeorientalis (Brassicaceae) and Salviaaethiopis (Lamiaceae) in northern and
      northwestern Kyrgyzstan is recorded. The first record of Chenopodiumvulvaria
      (Amaranthaceae) from the northern side of Kyrgyz Range is confirmed, and the
      species was found for the second time in Alay Range. The ephemerous occurrence of
      Hirschfeldiaincana (Brassicaceae) in Central Asia is recorded for the first time
      from Fergana Range. Tragusracemosus (Poaceae) is first recorded from the Chuy
      Depression as an ephemerous alien. Arrhenatherumelatius, escaped from cultivation
      and locally established, is new to the country. The second record of established
      occurrence of Centaureasolstitialis (Asteraceae) and an ephemerous occurrence of
      Glauciumcorniculatum (Papaveraceae) are presented. Complete information is
      collected about the occurrence of every mentioned species in Kyrgyzstan. 

PMID- 24855434
TI  - Studies in hawaiian Diptera I: new distributional records for endemic asteia
      (asteiidae).
AB  - New island records are reported for five species of Asteia endemic to the
      Hawaiian Islands (Asteiahawaiiensis, Asteiamauiensis, Asteiamolokaiensis,
      Asteiapalikuensis, Asteiasabroskyi). These new records expand our understanding
      of distributions in Asteia, change the percentage of single island endemics from
      78% to 33%, and have significance in how we view the process of diversification
      acting in this lineage. We also present a list of the known rearing records for
      two species in this group. Asteiamontgomeryi has been recorded from Erythrina and
      Asteiasabroskyi has been reared from Pisonia, Urera, Charpentiera and
      Hibiscadelphus. 

PMID- 24855437
TI  - Postiaalni Niemela & Vampola (Basidiomycota, Polyporales) - member of the
      problematic Postiacaesia complex - has been found for the first time in Hungary.
AB  - Due to their bluish basidiocarps the Postiacaesia (syn. Oligoporuscaesius)
      complex forms a distinctive morphological group within the polypore genus Postia
      Fr., 1874. Five species of this group occur in Europe: Postiaalni Niemela &
      Vampola, Postiacaesia (Schrad.) P. Karst., Postialuteocaesia (A. David) Julich,
      Postiamediterraneocaesia M. Pierre & B. Rivoire and Postiasubcaesia (A. David)
      Julich. In this study Postiaalni is reported for the first time from Hungary. The
      dichotomous key of the species of the European Postiacaesia complex was prepared
      as well. 

PMID- 24855436
TI  - Polytraits: A database on biological traits of marine polychaetes.
AB  - The study of ecosystem functioning - the role which organisms play in an
      ecosystem - is becoming increasingly important in marine ecological research. The
      functional structure of a community can be represented by a set of functional
      traits assigned to behavioural, reproductive and morphological characteristics.
      The collection of these traits from the literature is however a laborious and
      time-consuming process, and gaps of knowledge and restricted availability of
      literature are a common problem. Trait data are not yet readily being shared by
      research communities, and even if they are, a lack of trait data repositories and
      standards for data formats leads to the publication of trait information in forms
      which cannot be processed by computers. This paper describes Polytraits
      (http://polytraits.lifewatchgreece.eu), a database on biological traits of marine
      polychaetes (bristle worms, Polychaeta: Annelida). At present, the database
      contains almost 20,000 records on morphological, behavioural and reproductive
      characteristics of more than 1,000 marine polychaete species, all referenced by
      literature sources. All data can be freely accessed through the project website
      in different ways and formats, both human-readable and machine-readable, and have
      been submitted to the Encyclopedia of Life for archival and integration with
      trait information from other sources. 

PMID- 24855438
TI  - Morphological and geographical traits of the british odonata.
AB  - Trait data are fundamental for many aspects of ecological research, particularly
      for modeling species response to environmental change. We synthesised information
      from the literature (mainly field guides) and direct measurements from museum
      specimens, providing a comprehensive dataset of 26 attributes, covering the 43
      resident species of Odonata in Britain. Traits included in this database range
      from morphological traits (e.g. body length) to attributes based on the
      distribution of the species (e.g. climatic restriction). We measured 11
      morphometric traits from five adult males and five adult females per species.
      Using digital callipers, these measurements were taken from dry museum specimens,
      all of which were wild caught individuals. Repeated measures were also taken to
      estimate measurement error. The trait data are stored in an online repository
      (https://github.com/BiologicalRecordsCentre/Odonata_traits), alongside R code
      designed to give an overview of the morphometric data, and to combine the
      morphometric data to the single value per trait per species data. 

PMID- 24855439
TI  - First record of Eggplant Mealybug, Coccidohystrixinsolita (Hemiptera:
      Pseudococcidae), on Guam: Potentially a major pest.
AB  - The eggplant mealybug, Coccidohystrixinsolita (Green) (Hemiptera:
      Pseudococcidae), is recorded from the island of Guam in the Mariana Islands for
      the first time. Factors indicating that this introduced mealybug has the
      potential to become a pest of economic importance for agriculture and
      horticulture on Guam are discussed. 

PMID- 24855440
TI  - Ichneumonidae (Hymenoptera) species new to the fauna of Norway.
AB  - The present paper contains new distributional records for 61 species of ichneumon
      wasps (Hymenoptera, Ichneumonidae) previously unknown for Norway, six of them are
      reported from Scandinavia for the first time. 

PMID- 24855441
TI  - Tree diversity of the Dja Faunal Reserve, southeastern Cameroon.
AB  - The Dja Faunal Reserve located in southeastern Cameroon represents the largest
      and best protected rainforest patch in Cameroon. Here we make available a dataset
      on the inventory of tree species collected across the Dja. For this study nine 5
      km long and 5 m wide transects were installed. All species with a diameter at
      breast height greater than 10 cm were recorded, identified and measured. A total
      of 11546 individuals were recorded, corresponding to a total of 312 species
      identified with 60 genera containing unidentified taxa. Of the 54 identified
      families Fabaceae, Rubiaceae and Malvaceae were the most species rich, whereas
      Fabaceae, Phyllantaceae and Olacaceae were the most abundant. Finally,
      Tabernaemontanacrassa was the most abundant species across the Reserve. This
      dataset provides a unique insight into the tree diversity of the Dja Faunal
      Reserve and is now publically available and usable. 

PMID- 24855442
TI  - Note on some antlions from Mozambique (Neuroptera: Myrmeleontidae).
AB  - Faunal data concerning 4 poorly known species from Southern Mozambique are
      reported. Myrmeleonlanceolatus Rambur, 1842 is reported for the first time from
      Mozambique. 

PMID- 24855443
TI  - Spatial distribution of Madeira Island Laurisilva endemic spiders (Arachnida:
      Araneae).
AB  - Madeira island presents a unique spider diversity with a high number of endemic
      species, many of which are still poorly known. A recent biodiversity survey on
      the terrestrial arthropods of the native forest, Laurisilva, provided a large set
      of standardized samples from various patches throughout the island. Out of the
      fifty two species recorded, approximately 33.3% are Madeiran endemics, many of
      which had not been collected since their original description. Two new species to
      science are reported - Ceratinopsis n. sp. and Theridion n. sp. - and the first
      records of Poecilonetavariegata (Blackwall, 1841) and Tetragnathaintermedia
      Kulczynski, 1891 are reported for the first time for Madeira island.
      Considerations on species richness and abundance from different Laurisilva
      locations are presented, together with distribution maps for endemic species.
      These results contribute to a better understanding of spider diversity patterns
      and endemic species distribution in the native forest of Madeira island. 

PMID- 24855444
TI  - Evidence for the continued presence in New Zealand of Homotrysismacleayi
      (Borchmann, 1909) (Coleoptera: Tenebrionidae: Alleculinae).
AB  - The first detailed specimen records are presented for the Australian beetle
      Homotrysismacleayi (Borchmann, 1909) in New Zealand. Evaluation of this evidence
      clearly indicates that the species is fully established in the wild in New
      Zealand. It is therefore recommended that the species be added to the New Zealand
      Organisms Register (NZOR), as exotic and present in the wild. Some general
      comments are offered on the importance of data and evidence in faunistics. 

PMID- 24855445
TI  - First record of Orobdellakawakatsuorum (Hirudinida: Arhynchobdellida:
      Erpobdelliformes) from Kunashir Island, Kuril Islands.
AB  - Specimens of the genus Orobdella Oka, 1895 from Kunashir Island, the Kuril
      Islands, are identified as Orobdellakawakatsuorum Richardson, 1975. Mitochondrial
      tRNA(Leu) and ND1 data confirm the species identification of the Kunashir
      specimens. This is the first record of the genus Orobdella from the Kuril
      Islands. 

PMID- 24855446
TI  - Open source data logger for low-cost environmental monitoring.
AB  - The increasing transformation of biodiversity into a data-intensive science has
      seen numerous independent systems linked and aggregated into the current
      landscape of biodiversity informatics. This paper outlines how we can move
      forward with this programme, incorporating real time environmental monitoring
      into our methodology using low-power and low-cost computing platforms. 

PMID- 24855447
TI  - DNA barcoding reveals a new record of Potamogeton distinctus (Potamogetonaceae)
      and its natural hybrids, P. distinctus x P. nodosus and P. distinctus x P.
      wrightii ) (P. x malainoides) from Myanmar.
AB  - Indo-China floristic region is among the 34 richest floristic regions of the
      world, and its plant diversity is still under investigation. Here we report a new
      record of an aquatic plant, Potamogetondistinctus, from Myanmar, a part of the
      region, that is detected by means of DNA barcoding method. The molecular method
      further identified the other specimens as hybrids of Potamogeton: one is
      Potamogeton*malainoides (Potamogetondistinctus * Potamogetonwrightii), and the
      other is Potamogetondistinctus * Potamogetonnodosus. The first of these was thus
      far genetically confirmed in China, but the parental combination of the hybrid in
      Myanmar was reciprocal to those reported from China. The second hybrid was also
      recorded from China, but the maternal lineage was revealed for the first time, in
      this case it was Potamogetondistinctus. The present study showed that 1) nrITS is
      useful to distinguish closely related Potamogeton species as well as hybrids
      among them and 2) atpB-rbcL has higher utility than other frequently used plastid
      DNA markers. We thus propose nrITS and atpB-rbcL as DNA barcoding markers for
      future Potamogeton studies. 

PMID- 24855448
TI  - A new carpenter ant, Camponotusparabarbatus (Hymenoptera: Formicidae) from India.
AB  - A new species of carpenter ant, collected in the Shivalik range of Himalaya is
      described and illustrated based on the worker and gyne castes under the name
      Camponotusparabarbatus sp. n. Presence of dense, short setae on gena and ventral
      surface of head resembles it most to Camponotusbarbatus Roger, 1863 distributed
      in Southeast Asia. A regional identification key of Camponotus species is
      provided from the Shivalik hills of Indian Himalaya. 

PMID- 24855449
TI  - MEMS based Low Cost Piezoresistive Microcantilever Force Sensor and Sensor
      Module.
AB  - In the present work, we report fabrication and characterization of a low-cost
      MEMS based piezoresistive micro-force sensor with SU-8 tip using laboratory made
      silicon-on-insulator (SOI) substrate. To prepare SOI wafer, silicon film (0.8 um
      thick) was deposited on an oxidized silicon wafer using RF magnetron sputtering
      technique. The films were deposited in Argon (Ar) ambient without external
      substrate heating. The material characteristics of the sputtered deposited
      silicon film and silicon film annealed at different temperatures (400-1050
      degrees C) were studied using atomic force microscopy (AFM) and X-ray diffraction
      (XRD) techniques. The residual stress of the films was measured as a function of
      annealing temperature. The stress of the as-deposited films was observed to be
      compressive and annealing the film above 1050 degrees C resulted in a tensile
      stress. The stress of the film decreased gradually with increase in annealing
      temperature. The fabricated cantilevers were 130 um in length, 40 um wide and 1.0
      um thick. A series of force-displacement curves were obtained using fabricated
      microcantilever with commercial AFM setup and the data were analyzed to get the
      spring constant and the sensitivity of the fabricated microcantilever. The
      measured spring constant and sensitivity of the sensor was 0.1488N/m and 2.7mV/N.
      The microcantilever force sensor was integrated with an electronic module that
      detects the change in resistance of the sensor with respect to the applied force
      and displays it on the computer screen.

PMID- 24855450
TI  - Sibling support and the educational prospects of young adults in Malawi.
AB  - BACKGROUND: Extended kin networks are an important social and economic resource
      in Africa. Existing research has focused primarily on intergenerational ties, but
      much less is known about "lateral" ties, such as those between siblings. In
      contexts of high adult mortality (i.e., fewer parents and grandparents) sibling
      interdependencies may assume heightened importance, especially during the
      transition to adulthood. OBJECTIVE: In this paper, we extend the resource
      dilution perspective that dominates research on sibling relationships in early
      childhood and propose an alternate framework in which siblings represent a source
      of economic support that contributes positively to educational outcomes at later
      stages of the life course. METHODS: We draw upon longitudinal data from young
      adults (age 15-18) in southern Malawi to assess the scope and magnitude of
      economic transfers among sibship sets. We then explore the relationships between
      sibship size, net economic transfers between siblings, and four measures of
      educational progress. RESULTS: First, exchanges of economic support between
      siblings are pervasive in the Malawian context and patterned, especially by birth
      order. Second, economic support from siblings is positively associated with
      educational attainment, as well as with the odds of being at grade level in
      school, both contemporaneously and prospectively. CONCLUSIONS: During young
      adulthood, economic support from siblings acts as a buffer against the negative
      association between sibship size and schooling outcomes that has been documented
      at earlier ages. COMMENTS: We question the established notion that siblings
      unilaterally subtract from resource pools, and argue that sibling support may be
      consequential for a wide range of demographic outcomes in a variety of cultural
      contexts. Our findings point to the need for additional research on the
      importance of lateral kinship ties across cultural settings and throughout the
      life course.

PMID- 24855451
TI  - Bereaved family member perceptions of patient-focused family-centred care during
      the last 30 days of life using a mortality follow-back survey: does location
      matter?
AB  - BACKGROUND: Improving end-of-life care is an important international issue.
      Recently Nova Scotia researchers conducted a mortality follow-back survey to
      provide a population-based description of care provided to adults during their
      last 30 days of life as perceived by knowledgeable bereaved family members. Here
      we describe the relationship between the location where the decedent received the
      majority of care during their last 30 days and the informant's perception of the
      extent of unmet need, as defined by multiple domains of patient-focused, family
      centred care. METHOD: Death certificate identified informants (next-of-kin) of
      eligible adults who died between June 2009 and May 2011, in Nova Scotia, Canada
      were invited to participate in a telephone interview based on the After-Death
      Bereaved Family Member Interview. Whether or not the informant expressed unmet
      need or concerns for six patient-focused, family-centred care domains were
      assessed in relation to the location where the majority of care occurred during
      the decedent's last 30 days. RESULTS: 1358 informants took part (25% response
      rate). Results of 1316 eligible interviews indicated home (39%) was the most
      common location of care, followed by long-term care (29%), hospital (23%) and
      hospital-based palliative-care units (9%). Unmet need ranged from 5.6% for
      dyspnea help to 66% for the emotional and spiritual needs of the family. Although
      the mean score for overall satisfaction was high (mean = 8.7 in 1-10 scale; SD
      1.8), 57% were not completely satisfied. Compared to home, adjusted results
      indicated greater dissatisfaction with overall care and greater communication
      concerns in the hospital. Greater unmet need occurred at home for dyspnea. Less
      overall dissatisfaction and unmet need were expressed about care provided in long
      term care facilities and hospital-based palliative-care units. CONCLUSION:
      Bereaved informants were generally highly satisfied with the decedent's care
      during their last 30 days but variations were evident. Overall, no one location
      stood out as exceptionally different in terms of perceived unmet need within each
      of the patient-focused, family-centred care domains. Communication in various
      forms and family emotional and spiritual support were consistently viewed as
      lacking in all locations and identified as targeted areas for impacting quality
      care at end of life.

PMID- 24855452
TI  - Evaluation of a solid matrix for collection and ambient storage of RNA from whole
      blood.
AB  - BACKGROUND: Whole blood gene expression-based molecular diagnostic tests are
      becoming increasingly available. Conventional tube-based methods for obtaining
      RNA from whole blood can be limited by phlebotomy, volume requirements, and RNA
      stability during transport and storage. A dried blood spot matrix for collecting
      high-quality RNA, called RNA Stabilizing Matrix (RSM), was evaluated against
      PAXgene(r) blood collection tubes. METHODS: Whole blood was collected from 25
      individuals and subjected to 3 sample storage conditions: 18 hours at either room
      temperature (baseline arm) or 37 degrees C, and 6 days at room temperature. RNA
      was extracted and assessed for integrity by Agilent Bioanalyzer, and gene
      expression was compared by RT-qPCR across 23 mRNAs comprising a clinical test for
      obstructive coronary artery disease. RESULTS: RSM produced RNA of relatively high
      integrity across the various tested conditions (mean RIN +/- 95% CI: baseline
      arm, 6.92 +/- 0.24; 37 degrees C arm, 5.98 +/- 0.48; 6-day arm, 6.72 +/- 0.23).
      PAXgene samples showed comparable RNA integrity in both baseline and 37 degrees C
      arms (8.42 +/- 0.17; 7.92 +/- 0.1 respectively) however significant degradation
      was observed in the 6-day arm (3.19 +/- 1.32). Gene expression scores on RSM were
      highly correlated between the baseline and 37 degrees C and 6-day study arms
      (median r = 0.96, 0.95 respectively), as was the correlation to PAXgene tubes
      (median r = 0.95, p < 0.001). CONCLUSION: RNA obtained from RSM shows little
      degradation and comparable RT-qPCR performance to PAXgene RNA for the 23 genes
      analyzed. Further development of this technology may provide a convenient method
      for collecting, shipping, and storing RNA for gene expression assays.

PMID- 24855454
TI  - Differential regulation of anti-inflammatory genes by p38 MAP kinase and MAP
      kinase kinase 6.
AB  - BACKGROUND: Conventional p38alpha inhibitors have limited efficacy in rheumatoid
      arthritis, possibly because p38 blockade suppresses the counter-regulatory
      mechanisms that limit inflammation. In contrast, targeting the upstream MAP
      kinase kinases, MKK3 and MKK6, partially maintains p38-mediated anti-inflammatory
      responses in bone marrow-derived macrophages (BMDM). In this study, we explored
      the mechanisms that preserve anti-inflammatory gene expression by evaluating
      differential regulation of IL-10 and p38-dependent anti-inflammatory genes in
      MKK3-/-, MKK6-/-, and p38 inhibitor-treated wildtype cells. METHODS: BMDM from
      wild type (WT), MKK3-/-, and MKK6-/- mice were pre-treated with p38 inhibitor
      SB203580 (SB), JNK inhibitor SP600125 (SP), and/or ERK inhibitor PD98059 (PD) and
      stimulated with LPS. Supernatant protein levels were measured by multiplex bead
      immunoassay. mRNA expression was determined by qPCR and protein expression by
      Western blot analysis. De novo IL-10 mRNA synthesis was quantified in cells
      treated with ethynyl-uridine and LPS followed by reverse transcription and qPCR.
      mRNA half-life was measured in LPS-treated cells that were then incubated with
      actinomycin D +/- SB203580. RESULTS: Pre-treatment of WT BMDM with p38 inhibitor
      significantly reduced IL-10 production in the three groups, while ERK and JNK
      inhibitors had minimal effects. IL-10 production was significantly decreased in
      MKK3-/- BMDM compared with either WT or MKK6-/- cells. IL-10 mRNA expression was
      modestly reduced in MKK3-/- BMDM but was preserved in MKK6-/- cells compared with
      WT. De novo IL-10 mRNA synthesis was inhibited in MKK3-/- and p38 inhibitor pre
      treated cells, but not MKK6-/- cells compared with WT. IL-10 mRNA half-life was
      markedly reduced in p38 inhibitor-treated WT cells while MKK-deficiency had
      minimal effect. DUSP1 mRNA levels were preserved in MKK-deficient cells but not
      in p38 inhibitor-treated WT cells. Tristetraprolin mRNA and protein levels were
      reduced in p38 inhibitor-treated WT cells compared with MKK6-/- cells.
      CONCLUSION: Unlike p38-inhibition, the absence of MKK6 mostly preserves IL-10 and
      TTP protein expression in BMDM. MKK6-deficiency also spares DUSP1 and IL-1RA,
      which are key negative regulators of the inflammatory response. Together, these
      data suggest that MKK6 is a potential therapeutic target in RA.

PMID- 24855453
TI  - The synergistic effect of homocysteine and lipopolysaccharide on the
      differentiation and conversion of raw264.7 macrophages.
AB  - BACKGROUND: Macrophages play pivotal roles in the progression of atherosclerosis
      (AS) and their heterogeneous differentiation patterns have been studied
      extensively. The classical subtype of activated macrophage, M1, promotes the
      progression of AS. Conversely, the alternative subtype of activated macrophage,
      M2, is regarded as a repressor of AS. Homocysteine (Hcy) may influence macrophage
      subtype polarization both in vivo and in vitro. Homocysteinemia (HHcy) is an
      independent risk factor in coronary heart disease and the effect of Hcy on
      macrophage differentiation has not been studied until now. METHODS: Different
      concentrations of Hcy in combination with a fixed concentration of
      lipopolysaccharide (LPS, 200 ng/mL) were used to treat RAW264.7 macrophages. Real
      time PCR was used to detect and quantify RNA transcripts indicative of M1 and M2
      differentiation. The efficacy and specificity for each chemical stimulant in
      inducing macrophage differentiation were also investigated. The M2 macrophages
      (anti-inflammatory subtype) induced using classical methods (IL-4, 10 ng/mL) were
      also treated with different concentrations of Hcy complemented with LPS. The
      synergistic effect of Hcy and LPS in the converting the M2 subtype to M1 was also
      studied. RESULTS: Macrophages can be induced to differentiate towards M1 by a
      combination of Hcy with LPS, with the strongest effect observed at an Hcy
      concentration of 50 MUmol/L. After inducing macrophages to the M2 subtype using
      IL-4, treatment with both Hcy and LPS could elicit conversion from the M2 to M1
      subtype. CONCLUSION: Combined treatment with Hcy and LPS can induce the
      polarization of cultured RAW264.7 macrophages into the pro-inflammatory subtype,
      as well as promote subtype conversion from anti-inflammatory to pro-inflammatory.

PMID- 24855455
TI  - Proteomic analysis of Staphylococcus aureus biofilm cells grown under
      physiologically relevant fluid shear stress conditions.
AB  - BACKGROUND: The biofilm forming bacterium Staphylococcus aureus is responsible
      for maladies ranging from severe skin infection to major diseases such as
      bacteremia, endocarditis and osteomyelitis. A flow displacement system was used
      to grow S. aureus biofilms in four physiologically relevant fluid shear rates
      (50, 100, 500 and 1000 s(-1)) to identify proteins that are associated with
      biofilm. RESULTS: Global protein expressions from the membrane and cytosolic
      fractions of S. aureus biofilm cells grown under the above shear rate conditions
      are reported. Sixteen proteins in the membrane-enriched fraction and eight
      proteins in the cytosolic fraction showed significantly altered expression (p <
      0.05) under increasing fluid shear. These 24 proteins were identified using nano
      LC-ESI-MS/MS. They were found to be associated with various metabolic functions
      such as glycolysis / TCA pathways, protein synthesis and stress tolerance.
      Increased fluid shear stress did not influence the expression of two important
      surface binding proteins: fibronectin-binding and collagen-binding proteins.
      CONCLUSIONS: The reported data suggest that while the general metabolic function
      of the sessile bacteria is minimal under high fluid shear stress conditions, they
      seem to retain the binding capacity to initiate new infections.

PMID- 24855456
TI  - Multi-criteria decision analysis of breast cancer control in low- and middle-
      income countries: development of a rating tool for policy makers.
AB  - BACKGROUND: The objective of this study was to develop a rating tool for policy
      makers to prioritize breast cancer interventions in low- and middle- income
      countries (LMICs), based on a simple multi-criteria decision analysis (MCDA)
      approach. The definition and identification of criteria play a key role in MCDA,
      and our rating tool could be used as part of a broader priority setting exercise
      in a local setting. This tool may contribute to a more transparent priority
      setting process and fairer decision-making in future breast cancer policy
      development. METHODS: First, an expert panel (n = 5) discussed key considerations
      for tool development. A literature review followed to inventory all relevant
      criteria and construct an initial set of criteria. A Delphi study was then
      performed and questionnaires used to discuss a final list of criteria with clear
      definitions and potential scoring scales. For this Delphi study, multiple breast
      cancer policy and priority-setting experts from different LMICs were selected and
      invited by the World Health Organization. Fifteen international experts
      participated in all three Delphi rounds to assess and evaluate each criterion.
      RESULTS: This study resulted in a preliminary rating tool for assessing breast
      cancer interventions in LMICs. The tool consists of 10 carefully crafted criteria
      (effectiveness, quality of the evidence, magnitude of individual health impact,
      acceptability, cost-effectiveness, technical complexity, affordability, safety,
      geographical coverage, and accessibility), with clear definitions and potential
      scoring scales. CONCLUSIONS: This study describes the development of a rating
      tool to assess breast cancer interventions in LMICs. Our tool can offer
      supporting knowledge for the use or development of rating tools as part of a
      broader (MCDA based) priority setting exercise in local settings. Further steps
      for improving the tool are proposed and should lead to its useful adoption in
      LMICs.

PMID- 24855457
TI  - Using mortality follow-up of surveys to estimate social inequalities in healthy
      life years.
AB  - BACKGROUND: The estimation of healthy life years (HLY) by socio-economic status
      (SES) requires two types of data: the prevalence of activity limitation by SES
      generally extracted from surveys and mortality rates by SES generally derived
      from a linkage between the SES information in population databases (census,
      register) and mortality records. In some situations, no population-wide databases
      are available to produce mortality rates by SES, and therefore some alternatives
      must be explored. This paper assesses the validity of calculating HLY by SES
      using mortality rates derived from a linkage between surveys and mortality
      records. METHODS: TWO SURVEYS WERE CHOSEN TO EXPLORE THE VALIDITY OF THE PROPOSED
      APPROACH: The Belgian Health Interview Survey (HIS) and the Belgian Survey on
      Income and Living Conditions (SILC). The mortality follow-up of these surveys
      were used to calculate HLY by educational level at age 25. These HLY were
      compared with HLY estimates calculated using the mortality follow-up of the 2001
      census. The validity of this approach was evaluated against two criteria. First,
      the HLY calculated using the census and those calculated using the surveys must
      not be significantly different. Second, survey-based HLY must show significant
      social inequalities since such inequalities have been consistently reported with
      census-based HLY. RESULTS: Both criteria were met. First, for each educational
      category, no statistically significant difference was found when comparing census
      based and survey-based HLY estimates. For instance, men in the lowest educational
      category have shown a HLY of 34 years according to the HIS, and while this figure
      was 35.5 years according to the census, this difference was not statistically
      significant. Second, the survey-based HLY have shown a significant social
      gradient. For instance, men in the highest educational category are expected to
      live 9.5 more HLY than their counterparts in the lowest educational category
      based on the HIS estimates, compared with 7.3 HLY based on the census estimates.
      CONCLUSIONS: This article suggests that using the mortality follow-up of a
      nationally representative cross-sectional survey is a valid approach to monitor
      social inequalities in HLY in the absence of population-wide data.

PMID- 24855459
TI  - Facile molten salt synthesis of Li2NiTiO4 cathode material for Li-ion batteries.
AB  - Well-crystallized Li2NiTiO4 nanoparticles are rapidly synthesized by a molten
      salt method using a mixture of NaCl and KCl salts. X-ray diffraction pattern and
      scanning electron microscopic image show that Li2NiTiO4 has a cubic rock salt
      structure with an average particle size of ca. 50 nm. Conductive carbon-coated
      Li2NiTiO4 is obtained by a facile ball milling method. As a novel 4 V positive
      cathode material for Li-ion batteries, the Li2NiTiO4/C delivers high discharge
      capacities of 115 mAh g(-1) at room temperature and 138 mAh g(-1) and 50 degrees
      C, along with a superior cyclability. 

PMID- 24855458
TI  - Effects of carbohydrate combined with caffeine on repeated sprint cycling and
      agility performance in female athletes.
AB  - BACKGROUND: Caffeine (CAF) has been shown to improve performance during early
      phase of repeated sprint exercise; however some studies show that CAF also
      increases the magnitude of physical stress represented by augmented blood
      lactate, glucose, and cortisol concentrations during latter phase of repeated
      sprint exercise. No studies have investigated the efficacy of combined
      carbohydrate (CHO) and CAF consumption during repeated sprint exercise (RSE) in
      female athletes. Thus, the purpose of this study was to investigate the effects
      of CAF with CHO supplementation on RSE and agility. METHODS: Eleven female
      athletes completed four experimental trials performed 7 d apart in a double
      blind, randomized, and counter-balanced crossover design. Treatments included CAF
      + PLA (placebo), CAF + CHO, PLA + CHO, and PLA + PLA. Participants ingested
      capsules containing 6 mg . kg(-1) of CAF or PLA 60-min prior to RSE, and 0.8 g .
      kg(-1) of CHO solution or PLA immediately before the RSE, which consisted of ten
      sets of 5 * 4-s sprints on the cycle ergometer with 20-s active recovery. The
      agility T-test (AT-test) was performed before and after the RSE. Blood samples
      were acquired to assess glucose, lactate, testosterone, and cortisol. RESULTS:
      During Set 6 of RSE, peak power and mean power were significantly higher in PLA +
      CHO than those in CAF + PLA and PLA + PLA, respectively (p < .05). Total work was
      significantly increased by 4.8% and 5.9% with PLA + CHO than those of CAF + CHO
      and CAF + PLA during Set 3. PLA + CHO also increased total work more than CAF +
      PLA and PLA + PLA did during Set 6 (p < .05). No significant differences in AT
      test performance either before or after the RSE were occurred among treatments (p
      > .05). Blood lactate and glucose concentrations were significantly higher under
      CAF + CHO, CAF + PLA, and PLA + CHO versus PLA + PLA (p < .05), but no
      differences in testosterone or cortisol levels were found (p > .05). CONCLUSIONS:
      Findings indicate that CAF + PLA or CAF + CHO ingestion did not improve repeated
      sprint performance with short rest intervals or agility. However, CHO ingested
      immediately prior to exercise provided a small but significant benefit on RSE
      performance in female athletes.

PMID- 24855460
TI  - Cu-doped ZnO nanorod arrays: the effects of copper precursor and concentration.
AB  - Cu-doped ZnO nanorods have been grown at 90 degrees C for 90 min onto a quartz
      substrate pre-coated with a ZnO seed layer using a hydrothermal method. The
      influence of copper (Cu) precursor and concentration on the structural,
      morphological, and optical properties of ZnO nanorods was investigated. X-ray
      diffraction analysis revealed that the nanorods grown are highly crystalline with
      a hexagonal wurtzite crystal structure grown along the c-axis. The lattice strain
      is found to be compressive for all samples, where a minimum compressive strain of
      -0.114% was obtained when 1 at.% Cu was added from Cu(NO3)2. Scanning electron
      microscopy was used to investigate morphologies and the diameters of the grown
      nanorods. The morphological properties of the Cu-doped ZnO nanorods were
      influenced significantly by the presence of Cu impurities. Near-band edge (NBE)
      and a broad blue-green emission bands at around 378 and 545 nm, respectively,
      were observed in the photoluminescence spectra for all samples. The transmittance
      characteristics showed a slight increase in the visible range, where the total
      transmittance increased from approximately 80% for the nanorods doped with
      Cu(CH3COO)2 to approximately 90% for the nanorods that were doped with Cu(NO3)2. 

PMID- 24855461
TI  - Chemiluminescence behavior of CdTe-hydrogen peroxide enhanced by sodium
      hypochlorite and sensitized sensing of estrogens.
AB  - It has been found that sodium hypochlorite enhanced the chemiluminescence (CL) of
      the CdTe nanocrystal (NC)-hydrogen peroxide system and that estrogens inhibited
      these CL signals in alkaline solution. CL spectra were used to investigate the
      mechanism of the CL enhancement. On the basis of the inhibition, a flow-injection
      CL method has been established for determination of three natural estrogens. 

PMID- 24855462
TI  - Effect of In/Al ratios on structural and optical properties of InAlN films grown
      on Si(100) by RF-MOMBE.
AB  - In x Al1-x N films were deposited on Si(100) substrate using metal-organic
      molecular beam epitaxy. We investigated the effect of the
      trimethylindium/trimethylaluminum (TMIn/TMAl) flow ratios on the structural,
      morphological, and optical properties of In x Al1-x N films. Surface morphologies
      and microstructure of the In x Al1-x N films were measured by atomic force
      microscopy, scanning electron microscopy, X-ray diffraction (XRD), and
      transmission electron microscopy (TEM), respectively. Optical properties of all
      films were evaluated using an ultraviolet/visible/infrared (UV/Vis/IR) reflection
      spectrophotometer. XRD and TEM results indicated that In x Al1-x N films were
      preferentially oriented in the c-axis direction. Besides, the growth rates of In
      x Al1-x N films were measured at around 0.6 MUm/h in average. Reflection spectrum
      shows that the optical absorption of the In x Al1-x N films redshifts with an
      increase in the In composition. 

PMID- 24855463
TI  - A nontoxic and low-cost hydrothermal route for synthesis of hierarchical
      Cu2ZnSnS4 particles.
AB  - We explore a facile and nontoxic hydrothermal route for synthesis of a Cu2ZnSnS4
      nanocrystalline material by using l-cysteine as the sulfur source and
      ethylenediaminetetraacetic acid (EDTA) as the complexing agent. The effects of
      the amount of EDTA, the mole ratio of the three metal ions, and the hydrothermal
      temperature and time on the phase composition of the obtained product have been
      systematically investigated. The addition of EDTA and an excessive dose of ZnCl2
      in the hydrothermal reaction system favor the generation of kesterite Cu2ZnSnS4.
      Pure kesterite Cu2ZnSnS4 has been synthesized at 180 degrees C for 12 h from the
      reaction system containing 2 mmol of EDTA at 2:2:1 of Cu/Zn/Sn. It is confirmed
      by Raman spectroscopy that those binary and ternary phases are absent in the
      kesterite Cu2ZnSnS4 product. The kesterite Cu2ZnSnS4 material synthesized by the
      hydrothermal process consists of flower-like particles with 250 to 400 nm in
      size. It is revealed that the flower-like particles are assembled from single
      crystal Cu2ZnSnS4 nanoflakes with ca. 20 nm in size. The band gap of the
      Cu2ZnSnS4 nanocrystalline material is estimated to be 1.55 eV. The films
      fabricated from the hierarchical Cu2ZnSnS4 particles exhibit fast photocurrent
      responses under intermittent visible-light irradiation, implying that they show
      potentials for use in solar cells and photocatalysis. 

PMID- 24855464
TI  - Enhanced localization of anticancer drug in tumor tissue using polyethylenimine
      conjugated cationic liposomes.
AB  - Liposome-based drug delivery systems hold great potential for cancer therapy.
      However, to enhance the localization of payloads, an efficient method of systemic
      delivery of liposomes to tumor tissues is required. In this study, we developed
      cationic liposomes composed of polyethylenimine (PEI)-conjugated
      distearoylglycerophosphoethanolamine (DSPE) as an enhanced local drug delivery
      system. The particle size of DSPE-PEI liposomes was 130 +/- 10 nm and the zeta
      potential of liposomes was increased from -25 to 30 mV by the incorporation of
      cationic PEI onto the liposomal membrane. Intracellular uptake of DSPE-PEI
      liposomes by tumor cells was 14-fold higher than that of DSPE liposomes. After
      intratumoral injection of liposomes into tumor-bearing mice, DSPE-PEI liposomes
      showed higher and sustained localization in tumor tissue compared to DSPE
      liposomes. Taken together, our findings suggest that DSPE-PEI liposomes have the
      potential to be used as effective drug carriers for enhanced intracellular uptake
      and localization of anticancer drugs in tumor tissue through intratumoral
      injection. 

PMID- 24855465
TI  - An acetonitrile solvatomorph of di-chlorido-(1,10-phenanthroline-5,6
      dione)platinum(II).
AB  - In the title complex, [PtCl2(C12H6N2O2)].CH3CN, the Pt(II) atom lies in a
      slightly distorted square-planar arrangement defined by an N2Cl2 donor set. In
      the packed structure, columns of complex moieties are stacked such that the
      neighboring units are oriented at 180 degrees  and laterally displaced with
      respect to each other. This prevents any overlap of the phenanthroline rings and
      thus there is no possibility of any pi-pi inter-actions between aromatic rings. 

PMID- 24855466
TI  - Tri-MU-chlorido-bis-[(eta(5)-penta-methyl-cyclo-penta-dien-yl)rhodium(III)] hexa
      fluorido-phosphate from synchrotron radiation.
AB  - In the title complex salt, [{(eta(5)-C5Me5)Rh}2(MU-Cl)3]PF6, the dinuclear,
      single-charged cation is formed by the cojoining of two classic (eta(5)
      C5Me5)RhCl3 'piano-stool' units by bridging of the three choride ligand 'legs'.
      The crystal structure shows several close H?F contacts between the hexa-fluorido
      phosphate counter-ions and the C5Me5 ligands. 

PMID- 24855467
TI  - 5''-Benzyl-idene-5-chloro-1',1''-dimethyl-4'-phenyl-dispiro-[indoline-3,2'
      pyrrolidine-3',3''-piperidine]-2,4''-dione.
AB  - The title compound, C30H28ClN3O2, features two spiro links, one connecting the
      piperidine and pyrrolidine rings, and the other connecting the pyrrolidine ring
      and indole residue. The configuration about the ethene bond is E. The piperidine
      ring adopts a half-chair conformation where the C atom connected to the spiro-C
      atom lies 0.713 (3) A out of the plane of the remaining five atoms (r.m.s.
      deviation = 0.086 A). The pyrrolidine ring has an envelope conformation with the
      flap atom being the methyl-ene C atom. Centrosymmetric eight-membered {?HNCO}2
      amide synthons feature in the crystal packing. These are consolidated into a
      three-dimensional architecture by phen-yl-pyrrolidine C-H?N and chloro-benzene
      pyrrolidine-bound phenyl C-H?pi inter-actions. 

PMID- 24855468
TI  - 5-Chloro-5''-(4-chloro-benzyl-idene)-4'-(4-chloro-phen-yl)-1''-ethyl-1'-methyl
      dispiro-[indoline-3,2'-pyrrolidine-3',3''-piperidine]-2,4''-dione.
AB  - Two spiro links are found in the title compound, C31H28Cl3N3O2, one connecting
      the piperidine and pyrrolidine rings, and the other connecting the pyrrolidine
      ring and indole residue. The piperidine ring adopts a half-chair conformation, in
      which the C atom connected to the spiro-C atom lies 0.741 (3) A out of the plane
      of the remaining five atoms (r.m.s. deviation = 0.053 A). The pyrrolidine ring
      has an envelope conformation with the flap atom being the methyl-ene C atom.
      Centrosymmetric eight-membered {?HNCO}2 amide dimers are the most significant
      feature of the crystal packing. These are connected into layers parallel to (
      120) by C-H?O and pi-pi inter-actions between pyrrolidine-bound benzene rings
      [inter-centroid distance = 3.8348 (15) A]. Slipped face-to-face inter-actions
      between the edges of pyrrolidine-bound benzene [shortest C?C separation = 3.484
      (4) A] connect the layers into a three-dimensional architecture. 

PMID- 24855469
TI  - N-[(9H-Fluoren-9-yl-idene)(2-meth-oxy-phen-yl)meth-yl]-1,1,1-tri-methyl
      silanamine.
AB  - The title mol-ecule, C24H25NOSi, is a hydrolysis product of the reaction between
      9-tri-methyl-silyfluorenyl lithium and 2-meth-oxy-benzo-nitrile. The fluorene
      ring system is substanti-ally planar, with an r.m.s. deviation of 0.0288 A from
      the best-fit plane through its 13 C atoms. This plane forms a dihedral angle of
      58.07 (7) degrees  with the 2-meth-oxy-benzyl-amine ring plane. In the crystal,
      mol-ecules are linked by N-H?pi and C-H?pi inter-actions, which leads to the
      formation of two-dimensional network lying parallel to the bc plane. 

PMID- 24855470
TI  - 2-(5-Chloro-2-oxoindolin-3-yl-idene)hydrazinecarbo-thio-amide.
AB  - The title mol-ecule, C9H7ClN4OS, is almost planar, with an r.m.s. deviation of
      0.034 (2) A for the mean plane through all the non-H atoms. Intra-molecular N-H?O
      and N-H?N hydrogen bonds form S(6) and S(5) ring motifs, respectively. In the
      crystal, mol-ecules are assembled into inversion dimers through pairs of co
      operative N-H?Cl inter-actions. These dimers are connected along the b axis by N
      H?O and N-H?S hydrogen bonds, generating layers parallel to (103). The layers are
      further connected along the a axis into a three-dimensional network, through weak
      pi-pi stacking inter-actions [centroid-centroid distance = 3.849 (2) A]. 

PMID- 24855471
TI  - 5-Chloro-5''-[4-(di-methyl-amino)-benzyl-idene]-4'-[4-(di-methyl-amino)-phen-yl]
      1',1''-di-methyl-dispiro-[indoline-3,2'-pyrrolidine-3',3''-piperidine]-2,4''
      dione.
AB  - The title compound, C34H38ClN5O2, has spiro links connecting the pyrrolidine ring
      and indole residue, as well as the piperidine and pyrrolidine rings. A half-chair
      conformation is found for the piperidine ring with the C atom connected to the
      spiro-C atom lying 0.738 (4) A out of the plane of the remaining five atoms
      (r.m.s. deviation = 0.0407 A). The methyl-ene C atom is the flap in the envelope
      conformation for the pyrrolidine ring. In the crystal, supra-molecular chains are
      sustained by alternating eight-membered {?HNCO}2 and 14-membered {?HC5O}2
      synthons. Chains are connected into a three-dimensional network by (pyrrolidine
      bound phenyl-meth-yl)C-H?pi(pyrrolidine-bound phen-yl) edge-to-face inter
      actions. 

PMID- 24855472
TI  - 2,6-Bis[1-(2,4,6-tri-methyl-phenyl-imino)-eth-yl]pyridine.
AB  - In the title mol-ecule, C27H31N3, the imine C=N groups are orientated anti to the
      pyridine N atom, with N-C-C-N torsion angles of -164.91 (11) and -170.53 (10)
      degrees . In the crystal, mol-ecules are connected by weak C-H?N and C-H?pi inter
      actions parallel to the b axis. 

PMID- 24855473
TI  - Financial impact of health care-associated infections: When money talks.

PMID- 24855474
TI  - Prevention of vertical HIV transmission and management of the HIV-exposed infant
      in Canada in 2014.

PMID- 24855475
TI  - Characterization of methicillin-resistant Staphylococcus aureus isolates from
      patients with persistent or recurrent bacteremia.
AB  - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) bloodstream
      infections (BSI) are associated with considerable morbidity and mortality,
      especially with persistent (PB) or recurrent bacteremia (RB). OBJECTIVE: To
      determine the frequency of PB and RB in patients with MRSA BSI, and to
      characterize the isolates from these patients. METHODS: Surveillance for MRSA BSI
      was performed for one year in 13 Canadian hospitals. PB was defined as a positive
      blood culture that persisted for >=7 days; RB was defined as the recurrence of a
      positive blood culture >=14 days following a negative culture. Isolates were
      typed using pulsed-field gel electrophoresis (PFGE). Vancomycin susceptibility
      was determined using Etest. RESULTS: A total of 183 patients with MRSA BSI were
      identified; 14 (7.7%) had PB and five (2.7%) had RB. Ten (5.5%) patients were
      known to have infective endocarditis, and five of these patients had PB or RB.
      Initial and subsequent MRSA isolates from patients with PB and RB had the same
      PFGE type. There were no significant differences in the distribution of PFGE
      types in patients with PB or RB (37% CMRSA-2/USA100; 37% CMRSA-10/USA300)
      compared with that in other patients (56% CMRSA-2/USA100; 32% CMRSA-10/USA300).
      All isolates were susceptible to vancomycin, but patients with PB or RB were more
      likely to have initial isolates with vancomycin minimum inhibitory concentration
      = 2.0 MUg/mL (26% versus 10%; P=0.06). CONCLUSIONS: Persistent or recurrent MRSA
      bacteremia occurred in 10.4% of patients with MRSA BSIs. Initial isolates from
      patients with persistent or recurrent MRSA BSIs were more likely to exhibit
      reduced susceptibility to vancomcyin, but were not associated with any genotype.

PMID- 24855477
TI  - Variation in outpatient oral antimicrobial use patterns among Canadian provinces,
      2000 to 2010.
AB  - BACKGROUND: The volume and patterns of antimicrobial drug use are key variables
      to consider when developing guidelines for prescribing, and programs to address
      stewardship and combat the increasing prevalence of antimicrobial resistant
      pathogens. Because drug programs are regulated at the provincial level, there is
      an expectation that antibiotic use may vary among provinces. OBJECTIVE: To assess
      these potential differences according to province and time. METHODS: Provincial
      antimicrobial prescribing data at the individual drug level were acquired from
      the Canadian Integrated Program for Antimicrobial Resistance Surveillance for
      2000 to 2010. Data were used to calculate two yearly metrics: prescriptions per
      1000 inhabitant-days and the average defined daily doses per prescription. The
      proportion of liquid oral prescriptions of total prescriptions was also
      calculated as a proxy measure for the proportion of prescriptions given to
      children versus adults. To assess the significance of provincial antimicrobial
      use, linear mixed models were developed for each metric, accounting for repeated
      measurements over time. RESULTS: Significant differences among provinces were
      found, as well as significant changes in use over time. Newfoundland and Labrador
      was found to have significantly higher prescribing rates than all other provinces
      (P<0.001) in 2010, as well as the mean of all other provinces (P<0.001). In
      contrast, Quebec exhibited significantly lower prescribing than all other
      provinces (P<0.001 for all provinces except British Columbia, where P=0.024) and
      the mean of all other provinces (P<0.001). DISCUSSION/CONCLUSION: Reports of
      reductions in antimicrobial use at the Canadian level are promising, especially
      prescribing to children; however, care must be taken to avoid the pitfall of the
      ecological fallacy. Reductions are not consistent among the provinces or among
      the classes of antimicrobial drugs dispensed in Canada.

PMID- 24855476
TI  - Clinical and economic consequences of vancomycin and fidaxomicin for the
      treatment of Clostridium difficile infection in Canada.
AB  - BACKGROUND: Clostridium difficile infection (CDI) represents a public health
      problem with increasing incidence and severity. OBJECTIVE: To evaluate the
      clinical and economic consequences of vancomycin compared with fidaxomicin in the
      treatment of CDI from the Canadian health care system perspective. METHODS: A
      decision-tree model was developed to compare vancomycin and fidaxomicin for the
      treatment of severe CDI. The model assumed identical initial cure rates and
      included first recurrent episodes of CDI (base case). Treatment of patients
      presenting with recurrent CDI was examined as an alternative analysis. Costs
      included were for study medication, physician services and hospitalization. Cost
      effectiveness was measured as incremental cost per recurrence avoided.
      Sensitivity analyses of key input parameters were performed. RESULTS: In a cohort
      of 1000 patients with an initial episode of severe CDI, treatment with
      fidaxomicin led to 137 fewer recurrences at an incremental cost of $1.81 million,
      resulting in an incremental cost of $13,202 per recurrence avoided. Among 1000
      patients with recurrent CDI, 113 second recurrences were avoided at an
      incremental cost of $18,190 per second recurrence avoided. Incremental costs per
      recurrence avoided increased with increasing proportion of cases caused by the
      NAP1/B1/027 strain. Results were sensitive to variations in recurrence rates and
      treatment duration but were robust to variations in other parameters.
      CONCLUSIONS: The use of fidaxomicin is associated with a cost increase for the
      Canadian health care system. Clinical benefits of fidaxomicin compared with
      vancomycin depend on the proportion of cases caused by the NAP1/B1/027 strain in
      patients with severe CDI.

PMID- 24855478
TI  - Longitudinal surveillance of outpatient quinolone antimicrobial use in Canada.
AB  - INTRODUCTION: Because antimicrobial use is commonly associated with the
      development of antimicrobial resistance, monitoring the volume and patterns of
      use of these agents is important. OBJECTIVE: To assess the use of quinolone
      antimicrobials within Canadian provinces over time. METHODS: ANTIMICROBIAL
      PRESCRIBING DATA COLLECTED BY IMS HEALTH CANADA WERE ACQUIRED FROM THE CANADIAN
      INTEGRATED PROGRAM FOR ANTIMICROBIAL RESISTANCE SURVEILLANCE AND THE CANADIAN
      COMMITTEE FOR ANTIMICROBIAL RESISTANCE, AND WERE USED TO CALCULATE TWO YEARLY
      METRICS: prescriptions per 1000 inhabitant-days and the mean defined daily doses
      (DDDs) per prescription. These measures were used to produce linear mixed models
      to assess differences among provinces and over time, while accounting for
      repeated measurements. RESULTS: The quinolone class of antimicrobials is used
      similarly among Canadian provinces. Year-to-year increases in quinolone
      prescribing occurred from 1995 to 2010, with a levelling off in the latter years.
      Year-to-year decreases in the DDDs per prescription were found to be significant
      from 2000 to 2010. DISCUSSION: Although the overall use of antimicrobials differs
      significantly among Canadian provinces, the use of the quinolone class does not
      vary at the provincial level. Results suggest that prescribing of ciprofloxacin
      may be a potential target for antimicrobial stewardship programs; however,
      decreases in the average DDDs per prescription suggest continued uptake of
      appropriate treatment guidelines.

PMID- 24855479
TI  - Provincial and temporal variation in macrolide and lincosamide antimicrobial use
      by outpatients in Canada, 1995 to 2010.
AB  - INTRODUCTION: Because antimicrobial use is commonly associated with the
      development of antimicrobial resistance, monitoring the volume and patterns of
      use of these agents is very important. OBJECTIVE: To assess the use of macrolide
      and lincosamide (ML) antimicrobials within Canadian provinces over time, and to
      compare use rates with those reported by European countries. METHODS:
      ANTIMICROBIAL PRESCRIBING DATA WERE USED TO DEVELOP TWO YEARLY METRICS:
      prescriptions per 1000 inhabitant-days (PrIDs) and the mean defined daily doses
      (DDDs) per prescription, which were then used to build linear mixed models to
      assess differences among provinces over time. RESULTS: After accounting for
      repeated measures over time, prescribing rates (PrIDs) varied significantly
      according to province and year (P<0.001). However, little change occurred within
      each province over the time frame studied; from 1995 to 2010, each province had a
      PrID change <0.01. Quebec and British Columbia had significantly lower
      prescribing rates than all other provinces. No overall secular trend was
      apparent. In contrast, the DDDs per prescription did not vary significantly
      according to province, but showed a significant year-to-year increase.
      DISCUSSION: ML prescribing varied among provinces in Canada between 1995 and
      2010, but remained relatively stable within each province. The average DDDs per
      ML prescription did not vary according to province, but increased linearly over
      time. These increases are likely to indicate that fewer prescriptions are being
      written for children over time, a practice supported by good antimicrobial
      stewardship principles.

PMID- 24855480
TI  - Longitudinal surveillance of outpatient beta-lactam antimicrobial use in Canada,
      1995 to 2010.
AB  - INTRODUCTION: beta-lactam antimicrobials are the most commonly prescribed group
      of antimicrobials in Canada, and are categorized by the WHO as critically and
      highly important antimicrobials for human medicine. Because antimicrobial use is
      commonly associated with the development of antimicrobial resistance, monitoring
      the volume and patterns of use of these agents is highly important. OBJECTIVE: To
      assess the use of penicillin and cephalosporin antimicrobials within Canadian
      provinces over the 1995 to 2010 time frame according to two metrics:
      prescriptions per 1000 inhabitant-days and the average defined daily doses
      dispensed per prescription. METHODS: Antimicrobial prescribing data were acquired
      from the Canadian Integrated Program for Antimicrobial Resistance Surveillance
      and the Canadian Committee for Antimicrobial Resistance, and population data were
      obtained from Statistics Canada. The two measures developed were used to produce
      linear mixed models to assess differences among provinces and over time for the
      broad-spectrum penicillin and cephalosporin groups, while accounting for repeated
      measurements at the provincial level. RESULTS: Significant differences among
      provinces were found, as well as significant changes in use over time. A >28%
      reduction in broad-spectrum penicillin prescribing occurred in each province from
      1995 to 2010, and a >18% reduction in cephalosporin prescribing occurred in all
      provinces from 1995 to 2010, with the exception of Manitoba, where cephalosporin
      prescribing increased by 18%. DISCUSSION: Significant reductions in the use of
      these important drugs were observed across Canada from 1995 to 2010. Newfoundland
      and Labrador and Quebec emerged as divergent from the remaining provinces, with
      high and low use, respectively.

PMID- 24855481
TI  - Longitudinal surveillance of outpatient tetracycline, sulfonamide-trimethoprim
      and 'other' antimicrobial use in Canada, 1995 to 2010.
AB  - INTRODUCTION: Monitoring the volume and patterns of use of antimicrobial agents
      is important in light of antimicrobial resistance. OBJECTIVE: To assess the use
      of three antimicrobial groups - tetracycline, sulfonamide-trimethoprim and
      'other' antimicrobials - within Canadian provinces over time. METHODS:
      Prescription counts from 1995 to 2010 were acquired for the tetracycline and
      sulfonamide-trimethoprim groups of antimicrobials, and from 2001 to 2010 for the
      'other' antimicrobial group. Linear mixed models were produced to assess
      differences among provinces and over time while accounting for repeated
      measurements. Prescription rate, defined daily dose per 1000 inhabitant-days and
      defined daily doses per prescription measures for the year 2009 were also
      compared with those reported by participating European Union countries to
      determine where Canadian provinces rank in terms of antimicrobial use among these
      countries. RESULTS: Prescribing of all three groups varied according to province
      and over time. Tetracycline and sulfonamide-trimethoprim group prescribing were
      significantly reduced over the study period, by 36% and 61%, respectively.
      Prescribing of the 'other' antimicrobial group increased in all provinces from
      2001 to 2010 with the exception of Prince Edward Island, although by varying
      amounts (10% to 61% increases). DISCUSSION: The overall use of antimicrobials in
      Canada has dropped from 1995 to 2010, and the tetracycline and sulfonamide
      trimethoprim groups have contributed to this decline. The use of the 'other'
      antimicrobials has increased, however. These results may suggest that switches
      are being made among these groups, particularly among the antimicrobials used to
      treat urinary tract infections.

PMID- 24855482
TI  - Letter to the editor.

PMID- 24855484
TI  - Clinical features and outcomes of serotype 19A invasive pneumococcal disease in
      Calgary, Alberta.
AB  - The recent introduction of the seven-valent pneumococcal conjugate vaccine has
      led to changes in the proportion of disease caused by different serotypes. The
      serotypes targeted by the vaccine have been reduced, and Streptococcus pneumonia
      serotype 19A is now the most commonly isolated serotype causing invasive
      pneumococcal disease. This serotype has been associated with antibiotic
      resistance. The authors of this article conducted a review of cases of invasive
      pneumococcal disease diagnosed between 2000 and 2010 in Calgary, Alberta, to
      examine the disease course of serotype 19A invasive pneumococcal disease compared
      with other serotypes. BACKGROUND: Streptoccocus pneumoniae serotype 19A (ST19A)
      became an important cause of invasive pneumococcal disease (IPD) after the
      introduction of the conjugate vaccine. OBJECTIVE: To examine the severity and
      outcome of ST19A IPD compared with non-ST19A IPD. METHODS: The Calgary Area
      Streptococcus pneumoniae Epidemiology Research (CASPER) study collects clinical
      and laboratory data on all IPD cases in Calgary, Alberta. Analysis was performed
      on data from 2000 to 2010 comparing ST19A and non-ST19A IPD cases. Adjusted
      linear and logistic regression models were used to examine outcomes of duration
      of appropriate intravenous antibiotic therapy and intensive care unit admission,
      respectively. RESULTS: ST19A tended to cause disease in younger patients. ST19A
      isolates were more often multidrug resistant (19% versus 0.3%; P<0.001). Adjusted
      logistic regression showed no difference in intensive care unit admission between
      ST19A and non-ST19A IPD cases (OR 1.4 [95% CI 0.8 to 2.7]). An adjusted linear
      regression model showed patients <18 years of age with a diagnosis of bacteremia
      and no risk factors infected with ST19A were, on average, treated with
      antibiotics 1.4 times (95% CI 1.1 to 1.9) as long as patients with non-19A IPD
      and the same baseline characteristics. DISCUSSION: ST19A IPD was associated with
      an increase in average time on antibiotics. Although many of the infecting
      strains of ST19A were within the threshold for susceptibility, they may be
      sufficiently resilient to require a longer duration of antibiotic therapy or
      higher dose to clear the infection. CONCLUSIONS: ST19A is more common in younger
      individuals, is more antibiotic resistant and may require longer average
      treatment duration.

PMID- 24855485
TI  - Issues of methods and interpretation in the National Cancer Institute
      formaldehyde cohort study.
AB  - In 2004, the International Agency for Research on Cancer (IARC) reclassified
      formaldehyde (FA) from a probable (Group 2A) to a known human carcinogen (Group
      1) citing results for nasopharyngeal cancer (NPC) mortality from the follow-up
      through 1994 of the National Cancer Institute formaldehyde cohort study. To the
      contrary, in 2012, the Committee for Risk Assessment of the European Chemicals
      Agency disagreed with the proposal to classify FA as a known human carcinogen
      (Carc. 1A), proposing a lower but still protective category, namely as a
      substance which is presumed to have carcinogenic potential for humans (Carc. 1B).
      Thus, U.S. and European regulatory agencies currently disagree about the
      potential human carcinogenicity of FA. In 2013, the National Cancer Institute
      reported results from their follow-up through 2004 of the formaldehyde cohort and
      concluded that the results continue to suggest a link between FA exposure and
      NPC. We discuss in this commentary why we believe that this interpretation is
      neither consistent with the available data from the most recent update of the
      National Cancer Institute cohort study nor with other research findings from that
      cohort, other large cohort studies and the series of publications by some of the
      current authors, including an independent study of one of the National Cancer
      Institute's study plants. Another serious concern relates to the incorrectness of
      the data from the follow-up through 1994 of the National Cancer Institute study
      stemming from incomplete mortality ascertainment. While these data were corrected
      by the National Cancer Institute in subsequent supplemental publications,
      incorrect data from the original publications have been cited extensively in
      recent causal evaluations of FA, including IARC. We conclude that the NCI
      publications that contain incorrect data from the incomplete 1994 mortality
      follow-up should be retracted entirely or corrected via published errata in the
      corresponding journals, and efforts should be made to re-analyze data from the
      2004 follow-up of the NCI cohort study. 

PMID- 24855486
TI  - A novel approach to the generation of seamless constructs for plant
      transformation.
AB  - BACKGROUND: When creating plant transformation vectors, full control of
      nucleotides flanking the insert in the final construct may be desirable. Modern
      ligase-independent methods for DNA-recombination are based on linearization by
      classical type II restriction endonucleases (REs) alone or in combination with
      nicking enzymes leaving residual nucleotides behind in the final construct. We
      here explore the use of type IIS and type IIB REs for vector linearization that
      combined with sequence and ligase-independent cloning (SLIC) overcomes this
      problem and promotes seamless gene-insertion in vectors. Providing the basis for
      a collection of biolistic plant transformation vectors ready to be cloned with
      different genes-of-interest, we present two vectors, where promoter and
      terminator are joined by a spacer. During spacer-removal linearization (SRL),
      type IIS and type IIB REs remove their own recognition sequences from the vector
      leaving no undesired, short sequences behind. RESULTS: We designed two plant
      transformation vectors prepared for SRL in combination with SLIC, pAUrumII and
      pAUrumIII, harboring a spacer with recognition sites for a type IIS and IIB RE,
      respectively. The gene for a green fluorescent protein, gfp, was successfully
      cloned into both vectors; traces of pAUrumIII, however, contaminated the
      transformation due to incomplete linearization, an issue not encountered with the
      type IIS linearized pAUrumII. Both constructs, pAUrumII-gfp and pAUrumIII-gfp,
      were functional, when tested in vitro on wheat and barley endosperm cells for
      transient gfp expression. CONCLUSIONS: All nucleotides flanking an insert in a
      biolistic plant transformation vector can be customized by means of SRL in
      combination with SLIC. Especially type IIS REs promote an efficient cloning
      result. Based on our findings, we believe that the SRL system can be useful in a
      series of plant transformation vectors, favoring the presence of functional
      sequences for optimal expression over redundant cloning-site remnants.

PMID- 24855488
TI  - Transgenerational Consequences of Racial Discrimination for African American
      Health.
AB  - Disparities in African American health remain pervasive and persist
      transgenerationally. There is a growing consensus that both structural and
      interpersonal racial discrimination are key mechanisms affecting African American
      health. The Biopsychosocial Model of Racism as a Stressor posits that the
      persistent stress of experiencing discrimination take a physical toll on the
      health of African Americans and is ultimately manifested in the onset of illness.
      However, the degree to which the health consequences of racism and discrimination
      can be passed down from one generation to the next is an important avenue of
      exploration. In this review, we discuss and link literature across disciplines
      demonstrating the harmful impact of racism on African American physical health
      and the health of their offspring.

PMID- 24855489
TI  - After abduction: exploring access to reintegration programs and mental health
      status among young female abductees in Northern Uganda.
AB  - BACKGROUND: Reintegration programs are commonly offered to former combatants and
      abductees to acquire civilian status and support services to reintegrate into
      post-conflict society. Among a group of young female abductees in northern
      Uganda, this study examined access to post-abduction reintegration programming
      and tested for between group differences in mental health status among young
      women who had accessed reintegration programming compared to those who self
      reintegrated. METHODS: This cross-sectional study analysed interviews from 129
      young women who had previously been abducted by the Lords Resistance Army (LRA).
      Data was collected between June 2011-January 2012. Interviews collected
      information on abduction-related experiences including age and year of abduction,
      manner of departure, and reintegration status. Participants were coded as
      'reintegrated' if they reported >=1 of the following reintegration programs:
      traditional cleansing ceremony, received an amnesty certificate, reinsertion
      package, or had gone to a reception centre. A t-test was used to measure mean
      differences in depression and anxiety measured by the Acholi Psychosocial
      Assessment Instrument (APAI) to determine if abductees who participated in a
      reintegration program had different mental status from those who self
      reintegrated. RESULTS: From 129 young abductees, 56 (43.4%) had participated in a
      reintegration program. Participants had been abducted between 1988-2010 for an
      average length of one year, the median age of abduction was 13 years (IQR:11-14)
      with escaping (76.6%), being released (15.6%), and rescued (7.0%) being the most
      common manner of departure from the LRA. Traditional cleansing ceremonies (67.8%)
      were the most commonly accessed support followed by receiving amnesty (37.5%),
      going to a reception centre (28.6%) or receiving a reinsertion package (12.5%).
      Between group comparisons indicated that the mental health status of abductees
      who accessed >=1 reintegration program were not significantly different from
      those who self-reintegrated (p > 0.05). CONCLUSIONS: Over 40% of female abductees
      in this sample had accessed a reintegration program, however significant
      differences in mental health were not observed between those who accessed a
      reintegration program and those who self-reintegrated. The successful
      reintegration of combatants and abductees into their recipient community is a
      complex process and these results support the need for gender-specific services
      and ongoing evaluation of reintegration programming.

PMID- 24855490
TI  - Current concepts for oil decontamination of crush injuries: a review.
AB  - This anecdotal, non-systematic review serves to explore the principles and
      methods of effective oil decontamination from cutaneous wounds, particularly
      crush injuries. The current expansion of the petroleum industry is necessary to
      meet increasing world demands for oil. Most stages of oil refining and
      applications involve significant injury risks, particularly for crush injuries
      that become contaminated with petroleum compounds. A literature review regarding
      a standard of care for effective cutaneous oil decontamination is lacking. Based
      on case reports, animal models, and in vitro studies identified in our expert
      opinion review, standard water and soap cleansing may not be an appropriate
      approach. Instead, the principle of 'like dissolves like' guides the use of
      lipophilic, petroleum-derived solvents to attract and subsequently dissolve the
      petroleum contaminant from the skin injury. Limitations include paucity of and
      dated literature sources regarding the topic as well as no models specifically
      addressing crush injuries. Our literature review found that oil decontamination
      of cutaneous injuries may be best accomplished with oil-based cleansers.
      Certainly, this topic has significant importance for the potentially carcinogenic
      petroleum compounds that pervade virtually every aspect of modern human life. 

PMID- 24855487
TI  - Women's posttraumatic stress symptoms and autism spectrum disorder in their
      children.
AB  - Maternal posttraumatic stress disorder (PTSD) may be associated with autism
      spectrum disorder (ASD) in offspring through multiple pathways: maternal stress
      may affect the fetus; ASD in children may increase risk of PTSD in mothers; and
      the two disorders may share genetic risk. Understanding whether maternal PTSD is
      associated with child's ASD is important for clinicians treating children with
      ASD, as PTSD in parents is associated with poorer family functioning. We examined
      the association of maternal PTSD with offspring ASD in a large US cohort (N ASD
      cases = 413, N controls = 42,868). Mother's PTSD symptoms were strongly
      associated with child's ASD (RR 4-5 PTSD symptoms=1.98, 95% CI=1.39, 2.81; RR 6-7
      symptoms=2.89, 95% CI=2.00, 4.18). Clinicians treating persons with ASD should be
      aware of elevated risk of PTSD in the mother. Genetic studies should investigate
      PTSD risk alleles in relation to ASD.

PMID- 24855491
TI  - Virus against virus (VIVI): a potential solution against HIV/AIDS.
AB  - Most therapeutic regimens are aimed at the use of pharmacologic agents or the
      induction of immunological response against the pathological agent. However,
      these methods tend to be insufficient for the management of some of the most
      debilitating infectious diseases. Here we present a novel therapeutic approach.
      It involves voluntary super-infection of a subject having HIV/AIDS with a virus
      (GBV-C), which to date has not been shown to be responsible for any pathology. It
      has been shown to counter, suppress or eradicate the agent responsible for the
      severe disease. Several studies demonstrate the role of different micro-organisms
      in influencing the growth of other pathogens in the human body. This hypothesis
      requires meticulous testing before its implementation on humans. If the trials
      are successful, the implications for this hypothesis are promising considering
      the compliance issues and adverse effects associated with current standard of HIV
      care. 

PMID- 24855492
TI  - Reference values for toe grip strength among Japanese adults aged 20 to 79 years:
      a cross-sectional study.
AB  - BACKGROUND: No standardised method has been adopted for measuring toe-grip
      strength (TGS), and no reference values have been established for evaluating it.
      The present study investigated age-related changes in TGS and the association of
      TGS with various descriptive characteristics. METHODS: TGS was measured in both
      feet of 1842 community-dwelling individuals aged 20-79 years using a toe-grip
      dynamometer. The participants were classified by decade into six age groups: 20
      29, 30-39, 40-49, 50-59, 60-69, and 70-79 years. Correlations for TGS between the
      dominant and non-dominant sides were analysed according to decade and sex using
      Pearson's correlation coefficient. The mean TGS and TGS-to-weight ratio (TGS/Wt%)
      were compared between sexes by each decade and among all decades by sex using two
      way analysis of variance with post-hoc tests. To assess relationships between
      mean TGS and various descriptive characteristics, we determined Pearson's
      correlation coefficient by sex and performed a stepwise multiple-regression
      analysis. Significance was set at 5%. RESULTS: Correlations for TGS between the
      dominant and non-dominant sides were significant in all decades by sex, ranging
      from 0.73 for men in their 70s to 0.91 for women in their 50s. Mean TGS and
      TGS/Wt% significantly differed between the sexes in all decades and in all
      decades except the 40s, respectively. In men, the mean TGS and TGS/Wt%
      significantly decreased with aging after the 50s and 60s, respectively. In women,
      both the mean TGS and TGS/Wt% significantly decreased between the 40s and 50s and
      between the 60s and 70s. TGS significantly correlated with age, height, and
      weight in both sexes. The stepwise multiple-regression analysis revealed TGS was
      significantly associated with sex, age, height, and weight (adjusted R(2) =
      0.31). CONCLUSIONS: TGS was closely correlated between the dominant and non
      dominant sides. TGS and TGS/Wt were significantly reduced with aging after the
      50s in men and significantly reduced between the 40s and 50s and between the 60s
      and 70s in women. Age, sex, height, and weight accounted for only 30.8% of the
      variance in TGS. Therefore, other factors (e.g. toe flexibility, structural
      characteristics) should be considered for improving the accuracy of predicting
      TGS.

PMID- 24855494
TI  - Usage and applications of Semantic Web techniques and technologies to support
      chemistry research.
AB  - BACKGROUND: The drug discovery process is now highly dependent on the management,
      curation and integration of large amounts of potentially useful data. Semantics
      are necessary in order to interpret the information and derive knowledge.
      Advances in recent years have mitigated concerns that the lack of robust, usable
      tools has inhibited the adoption of methodologies based on semantics. RESULTS:
      THIS PAPER PRESENTS THREE EXAMPLES OF HOW SEMANTIC WEB TECHNIQUES AND
      TECHNOLOGIES CAN BE USED IN ORDER TO SUPPORT CHEMISTRY RESEARCH: a controlled
      vocabulary for quantities, units and symbols in physical chemistry; a controlled
      vocabulary for the classification and labelling of chemical substances and
      mixtures; and, a database of chemical identifiers. This paper also presents a Web
      based service that uses the datasets in order to assist with the completion of
      risk assessment forms, along with a discussion of the legal implications and
      value-proposition for the use of such a service. CONCLUSIONS: We have introduced
      the Semantic Web concepts, technologies, and methodologies that can be used to
      support chemistry research, and have demonstrated the application of those
      techniques in three areas very relevant to modern chemistry research, generating
      three new datasets that we offer as exemplars of an extensible portfolio of
      advanced data integration facilities. We have thereby established the importance
      of Semantic Web techniques and technologies for meeting Wild's fourth "grand
      challenge".

PMID- 24855493
TI  - Immunoexpression of aromatase cytochrome P450 and 17beta-hydroxysteroid
      dehydrogenase in women's ovaries after menopause.
AB  - BACKGROUND: Menopause results in a lack of regular menstrual cycles, leading to
      the reduction of estrogen production. On the other hand, ovarian androgen
      synthesis is still present at reduced levels and requires expression of several
      steroidogenic enzymes. METHODS: This study was performed on 104 postmenopausal
      women hospitalized due to uterine leiomyomas, endometriosis, and/or a prolapsed
      uterus. Patients were divided into three groups depending on the time from
      menopause. Group A patients experienced menopause 1-5 years before enrollment in
      the study (42 women). Group B included women who had their last menstruation 5-10
      years before the study (40 women). Group C consisted of 22 women who were more
      than 10 years past menopause. Hysterectomy or removal of the uterine corpus with
      adnexa was performed during laparotomy. We evaluated the expression of aromatase
      cytochrome P450 (CYP 19) and 17beta-hydroxysteroid dehydrogenase (17beta HSD) by
      employing immunohistochemistry. RESULTS: Activity of 17beta-HSD and CYP19 was
      demonstrated in the cytoplasm of stromal cells of postmenopausal ovaries,
      epithelium cells coating the ovaries, vascular endothelial cells, and epithelial
      inclusion cysts. However, overall expression of both 17beta-HSD and CYP 19
      decreased with time after menopause. CONCLUSION: Demonstration of the activity of
      the key enzymes of ovarian steroidogenesis, CYP 19 and 17beta-HSD, confirms
      steroidogenic activity in the ovaries of postmenopausal women. Nevertheless,
      ovarian steroidogenic activity decreases with time, and its significant decrease
      occurs 10 years after menopause.

PMID- 24855497
TI  - Effects of targets embedded within words in a visual search task.
AB  - Visual search performance can be negatively affected when both targets and
      distracters share a dimension relevant to the task. This study examined if visual
      search performance would be influenced by distracters that affect a dimension
      irrelevant from the task. In Experiment 1 within the letter string of a letter
      search task, target letters were embedded within a word. Experiment 2 compared
      targets embedded in words to targets embedded in nonwords. Experiment 3 compared
      targets embedded in words to a condition in which a word was present in a letter
      string, but the target letter, although in the letter string, was not embedded
      within the word. The results showed that visual search performance was negatively
      affected when a target appeared within a high frequency word. These results
      suggest that the interaction and effectiveness of distracters is not merely
      dependent upon common features of the target and distracters, but can be affected
      by word frequency (a dimension not related to the task demands). 

PMID- 24855496
TI  - Labelling Polymers and Micellar Nanoparticles via Initiation, Propagation and
      Termination with ROMP.
AB  - In this paper we compare and contrast three approaches for labelling polymers
      with functional groups via ring-opening metathesis polymerization (ROMP). We
      explored the incorporation of functionality via initiation, termination and
      propagation employing an array of novel initiators, termination agents and
      monomers. The goal was to allow the generation of selectively labelled and well
      defined polymers that would in turn lead to the formation of labelled
      nanomaterials. Norbornene analogues, prepared as functionalized monomers for
      ROMP, included fluorescent dyes (rhodamine, fluorescein, EDANS, and coumarin),
      quenchers (DABCYL), conjugatable moieties (NHS esters, pentafluorophenyl esters),
      and protected amines. In addition, a set of symmetrical olefins for terminally
      labelling polymers, and for the generation of initiators in situ is described.

PMID- 24855495
TI  - Diabetes and cardiovascular disease: from evidence to clinical practice -
      position statement 2014 of Brazilian Diabetes Society.
AB  - There is a very well known correlation between diabetes and cardiovascular
      disease but many health care professionals are just concerned with glycemic
      control, ignoring the paramount importance of controlling other risk factors
      involved in the pathogenesis of serious cardiovascular diseases. This Position
      Statement from the Brazilian Diabetes Society was developed to promote increased
      awareness in relation to six crucial topics dealing with diabetes and
      cardiovascular disease: Glicemic Control, Cardiovascular Risk Stratification and
      Screening Coronary Artery Disease, Treatment of Dyslipidemia, Hypertension,
      Antiplatelet Therapy and Myocardial Revascularization. The issue of what would be
      the best algorithm for the use of statins in diabetic patients received a special
      attention and a new Brazilian algorithm was developed by our editorial committee.
      This document contains 38 recommendations which were classified by their levels
      of evidence (A, B, C and D). The Editorial Committee included 22 specialists with
      recognized expertise in diabetes and cardiology. 

PMID- 24855498
TI  - Testing day: The effects of processing bias induced by Navon stimuli on the
      strength of the Muller-Lyer illusion.
AB  - Explanations for the cognitive basis of the Muller-Lyer illusion are still
      frustratingly mixed. To date, Day's (1989) theory of perceptual compromise has
      received little empirical attention. In this study, we examine the merit of Day's
      hypothesis for the Muller-Lyer illusion by biasing participants toward global or
      local visual processing through exposure to Navon (1977) stimuli, which are known
      to alter processing level preference for a short time. Participants (N = 306)
      were randomly allocated to global, local, or control conditions. Those in global
      or local conditions were exposed to Navon stimuli for 5 min and participants were
      required to report on the global or local stimulus features, respectively.
      Subsequently, participants completed a computerized Muller-Lyer experiment where
      they adjusted the length of a line to match an illusory-figure. The illusion was
      significantly stronger for participants with a global bias, and significantly
      weaker for those with a local bias, compared with the control condition. These
      findings provide empirical support for Day's "conflicting cues" theory of
      perceptual compromise in the Muller-Lyer illusion. 

PMID- 24855499
TI  - Absolute and relative pitch: Global versus local processing of chords.
AB  - Absolute pitch (AP) is the ability to identify or produce notes without any
      reference note. An ongoing debate exists regarding the benefits or disadvantages
      of AP in processing music. One of the main issues in this context is whether the
      categorical perception of pitch in AP possessors may interfere in processing
      tasks requiring relative pitch (RP). Previous studies, focusing mainly on melodic
      and interval perception, have obtained inconsistent results. The aim of the
      present study was to examine the effect of AP and RP separately, using isolated
      chords. Seventy-three musicians were categorized into four groups of high and low
      AP and RP, and were tested on two tasks: identifying chord types (Task 1), and
      identifying a single note within a chord (Task 2). A main effect of RP on Task 1
      and an interaction between AP and RP in reaction times were found. On Task 2 main
      effects of AP and RP, and an interaction were found, with highest performance in
      participants with both high AP and RP. Results suggest that AP and RP should be
      regarded as two different abilities, and that AP may slow down reaction times for
      tasks requiring global processing. 

PMID- 24855501
TI  - Design Challenges and Guidelines for Persuasive Technologies that Facilitate
      Healthy Lifestyles.
AB  - Many diseases and health risks are the result of unhealthy lifestyles and
      technology could be used as an intervention. However, designing healthy lifestyle
      technologies is challenging, as the technology should be able to influence user
      behavior. In this case study, the design and evaluation process of a persuasive
      healthy lifestyle assistance technology was investigated. The iterative design
      and evaluation process included: contextual inquiry, storyboarding, concept
      generation, paper prototyping, video prototyping, interactive prototyping and
      user testing. Several design challenges are identified and guidelines are
      described for designing a technological intervention to encourage healthy
      lifestyles.

PMID- 24855500
TI  - Sugar ingestion and dichotic listening: Increased perceptual capacity is more
      than motivation.
AB  - Participants ingested a sugar drink or a sugar-free drink and then engaged in a
      pair of dichotic listening tasks. Tasks presented category labels then played a
      series of word pairs, one in the left ear and one in the right. Participants
      attempted to identify pairs containing a target category member. Target category
      words were homonyms. For example, arms appeared as a target in the "body parts"
      category. Nontargets that played along with targets were related to a category
      appropriate version of the target (e.g., sleeves), a category-inappropriate
      version (e.g., weapons), or were unrelated to either version of the target (e.g.,
      plant). Hence, an effect of nontarget type on number of targets missed was
      evidence that participants processed nontargets for meaning. In the divided
      attention task, participants monitored both ears. In the focused attention task,
      participants monitored the left ear. Half the participants in each group had the
      divided attention task before the focused attention task; the other half had the
      focused attention task before the divided attention task. We set task lengths to
      about 12 min so working on the first task would give sufficient time for
      metabolizing sugar from the drink before the start of the second task. Nontarget
      word type significantly affected targets missed in both tasks. Drink type
      affected performance in the divided attention task only after sufficient time for
      converting sugar into blood glucose. The result supports an energy model for the
      effect of sugar ingestion on perceptual tasks rather than a motivational model. 

PMID- 24855502
TI  - Repeated use of albuterol inhaler as a potential cause of Takotsubo
      cardiomyopathy.
AB  - PATIENT: Female, 78 FINAL DIAGNOSIS: Takotsubo cardiomyopathy Symptoms: Chest
      discomfort, chest pain, dyspnea, short of breath Medication: - Clinical
      Procedure: - Specialty: Cardiology. OBJECTIVE: Unusual or unexpected effect of
      treatment. BACKGROUND: Takotsubo cardiomyopathy is an increasingly recognized
      cardiac condition that usually results from an acute stressor. Some medications
      are becoming recognized as possible stressors. Albuterol is widely used in
      general medicine. We report an unusual link between Takotsubo cardiomyopathy and
      albuterol. CASE REPORT: A 78-year-old woman presented to our emergency department
      for chest pain of 2-day duration. The patient had been taking albuterol inhaler
      therapy for worsening shortness of breath followed by chest pain. Her albuterol
      use was excessive. There were no other acute stressors. The electrocardiogram
      showed ST-elevations in the anterior and inferior leads. Emergent coronary
      angiography showed noncritical coronary artery disease and left ventriculography
      showed apical ballooning. CONCLUSIONS: When patients taking albuterol present
      with acute chest pain in the absence of other etiologies, beta-agonist-induced
      Takotsubo cardiomyopathy should be considered.

PMID- 24855503
TI  - Mesenchymal stem cell delivery routes and fate.
AB  - MSC have been used in diverse animal disease models to investigate their
      regenerative capacity. Although the clinical outcome was often encouraging, the
      mode of action of the cells remains unresolved. Differentiation of MSC into cell
      types of their target organs was only rarely shown, with the exception of the
      musculoskeletal system. Thus, the effect of the cells on the clinical outcome in
      several disease models of tissue degeneration must be independent of trans
      differentiation and caused by indirect or paracrine effects. Furthermore,
      tracking of the cells in vivo revealed that only a small proportion of the cells
      home and persists in the target sites, and that most of the cells are not
      detectable after 7~14 days post transplantation. It seems that MSC can deliver a
      profound clinical effect without trans-differentiation, without homing to target
      organs in significant numbers and despite the cell's disappearance within short
      periods of time. These finding also suggest that the full potency of MSC has not
      yet been exploited in the current applications. Here we will provide an overview
      of the different routes used for cell delivery and the fate of the cells after
      transplantation. The effects on clinical outcome are discussed with respect to
      the role cell entrapment in non-target organs may play for the observed clinical
      effects. 

PMID- 24855507
TI  - Adipose stem cells as a clinically available and effective source of adult stem
      cell therapy.
AB  - The greatest advantage of adipose-derived stem cells (ASCs) over other types of
      adult stem cells is its large number when we harvest primarily. The number of
      ASCs within adipose tissue reaches more than hundreds of times compared with
      BMSCs contained in the same amount of bone marrow. The major role of
      'regenerative medicine' in 21st century is based on cell therapy and ASC is going
      to take the core position. It is important to know the characteristics of ASCs
      for successful clinical application. There are several unique features of ASCs
      which is known common characteristic of mesenchymal stem cells (MSCs). Cellular
      plasticity is one of the most important features of ASCs as in other adult stem
      cells and the cells also have a special function of immune modulation and
      immunosuppression. Strong angiogenic potential is another important nature of
      ASCs. In many reports, ASCs are known not only to be differentiated into
      osteoblasts, chondrocytes, vascular endothelial cells, but also to be
      cardiomyocytes and neuronal cells. In conclusion, the new knowledge of ASCs is
      going to impact on the regenerative medicine. To take the advantage of this new
      type of cells and utilize the cells, we need to understand the function of ASCs
      and future possibilities of ASCs. We plastic surgeons continue to stimulate the
      our curiosity and creativity, as well as our clinical inspiration. 

PMID- 24855506
TI  - New Concept of Neural Stem Cell Transplantation: Anti-inflammatory Role.
AB  - Neural stem cells (NSCs) transplantation has been studied as a promising tool for
      replacing damaged neurons in various neurological disorders. However, recent
      growing data showed new therapeutic benefits of NSCs, which is that transplanted
      NSCs can modulate cerebral inflammation and protect the brain from further
      degeneration. We review recent discoveries regarding to the anti-inflammatory
      effects of NSCs and their future perspectives. 

PMID- 24855504
TI  - Human adult stem cells as the target cells for the initiation of carcinogenesis
      and for the generation of "cancer stem cells".
AB  - The inference to stem cells has been found in ancient myths and the concept of
      stem cells has existed in the fields of plant biology, developmental biology and
      embryology for decades. In the field of cancer research, the stem cell theory was
      one of the earliest hypotheses on the origin of a cancer from a single cell.
      However, an opposing hypothesis had it that an adult differentiated somatic cell
      could "de-differentiate" to become a cancer cell. Only within the last decade,
      via the "cloning" of Dolly, the sheep, did the field of stem cell biology really
      trigger an exciting revolution in biological research. The isolation of human
      embryonic stem cells has created a true revolution in the life sciences that has
      led to the hope that these human stem cells could lead to (a) basic science
      understanding of gene regulation during differentiation and development; (b) stem
      cell therapy; (c) gene therapy via stem cells; (d) the use of stem cells for drug
      discovery; (e) screening for toxic effects of chemicals; and (f) understand the
      aging and diseases of aging processes. 

PMID- 24855508
TI  - Mesenchymal stem cells for treatment of myocardial infarction.
AB  - Cardiovascular diseases including myocardial infarction are one of the major
      causes of adult mortality. Several treatments such as pharmacological therapy and
      heart transplantation have been used for the diseases, but the treatments have
      drawbacks. Therefore, cell-based myocardial therapies have received proper
      medical attention. Bone marrow stem cell (BMSC) including mesenchymal stem cell
      (MSC) and hematopoietic stem cell (HSC) is a potential source for cell therapy
      for heart diseases due to the ability of BMSC to differentiate into cell in
      cardiac tissue including cardiomyocyte and vascular endothelial cell. This
      article reviews the use of BMSCs for cardiovascular disease and the
      differentiation of BMSCs into cardiaomyocytes. 

PMID- 24855505
TI  - Human nerual stem cells for brain repair.
AB  - Cell replacement therapy and gene transfer to the diseased or injured brain have
      provided the basis for the development of potentially powerful new therapeutic
      strategies for a broad spectrum of human neurological diseases including
      Parkinson disease, Huntington disease, amyotrophic lateral sclerosis (ALS),
      Alzheimer disease, multiple sclerosis (MS), stroke, spinal cord injury and brain
      cancer. In recent years, neurons and glial cells have successfully been generated
      from neural stem cells, and extensive efforts by investigators to develop neural
      stem cell-based transplantation therapies have been carried out. We review here
      notable experimental and pre-clinical studies we have previously conducted
      involving human neural stem cell-based cell- and gene-therapies for Parkinson
      disease, Huntington disease, ALS, stroke and brain cancer. 

PMID- 24855509
TI  - Age-related Deterioration of Hematopoietic Stem Cells.
AB  - Aging is the process of system deterioration over time in the whole body. Stem
      cells are self-renewing and therefore have been considered exempt from the aging
      process. Earlier studies by Hayflick showed that there is an intrinsic limit to
      the number of divisions that mammalian somatic cells can undergo, and cycling
      kinetics and ontogeny-related studies strongly suggest that even the most
      primitive stem cell functions exhibit a certain degree of aging. Despite these
      findings, studies on the effects of aging on stem cell functions are
      inconclusive. Here we review the age-related properties of hematopoietic stem
      cells in terms of intrinsic and extrinsic alterations, proliferative potential,
      signaling molecules, telomere and telomerase, senescence and cancer issues,
      regenerative potential and other indications of stem cell aging are discussed in
      detail. 

PMID- 24855510
TI  - Angiogenesis induced by autologous whole bone marrow stem cells transplantation.
AB  - BACKGROUND AND OBJECTIVES: It has been presumed that unknown cells and growth
      factors in bone marrow might promote angiogenesis, so angiogenesis effect could
      be enhanced by autologous whole bone marrow (WBM) stem cell transplantation. We
      compared capillary ratio induced by autologous WBM and bone marrow-mononuclear
      cells (BM-MNCs) to evaluate the anigiogenic effect of auotologous WBM. In
      addition, the combined effect of WBM transplantation and granulocyte colony
      stimulating factor (G-CSF) injection was examined in an ischemic canine model.
      METHODS AND RESULTS: After creating ischemic limb model, autologous WBM and
      isolated BM-MNCs were transplanted into the ischemic muscle. In other
      experiments, autologous WBM with recombinant human G-CSF (rhG-CSF) and autologous
      WBM without rhG-CSF were transplanted into the ischemic muscle. In this study,
      normal saline was injected into the contralateral sites in each ischemic model as
      a control group. After 8 weeks of transplantation, angiography and muscle harvest
      were performed, and then the anigiographic findings and capillary density, as
      assessed by immunohistochemical staining, were investigated and analyzed. In
      comparison with the control group, BM-MNCs and WBM transplantation groups showed
      higher ratios of the capillary density (1.5+/-0.01 times, p<0.001 and 1.6+/-0.15
      times, p=0.005, respectively). Between the BM-MNCs and WBM transplantation
      groups, the capillary ratio was 1.2 folds higher in the WBM group than that in
      the BM-MNCs group, but there was no significantly different (p=0.116). The
      angiogensis ratios of both the WBM without G-CSF group and the WBM with G-CSF
      groups were higher (1.6+/-0.15 times, p=0.004 and 1.8 +/-0.01 times, p=0.005,
      respectively) than that of the control groups. In comparison with the WBM without
      G-CSF group, the WBM with G-CSF transplantation group revealed a 1.1 folds higher
      angiogenesis ratio, but there was no statistically significant difference
      (p=0.095). CONCLUSIONS: Autologous WBM transplantation is a simpler method and it
      is not inferior for inducing therapeutic angiogenesis as compared with isolated
      BM-MNCs transplantation. In addition to autologous WBM transplantation,
      intravenous G-CSF injection enhances the angiogenic effect of autologous WBM in
      an ischemic limb.

PMID- 24855512
TI  - Induction of Nestin-expressing Spheroids from Human Dermal Fibroblasts in a bFGF
      dependent Manner.
AB  - BACKGROUND AND OBJECTIVES: Neural stem/precursor cells are found in relatively
      inaccessible neurogenic regions of the adult brain, making them difficult to
      harvest for therapeutic purposes. METHODS AND RESULTS: In this study, nestin
      expressing spheroids were induced from primary cultures of newborn and adult
      foreskin-derived dermal fibroblasts using a novel, two-step induction method.
      Approximately 80% of dermal fibroblasts became nestin-expressing cells within 12
      days. Nestin expression and spheroid-forming capacity were both blocked by
      removal of bFGF from the induction medium. The bFGF-induced, nestin-expressing
      spheroids possessed most of the features distinctive of skin-derived precursor
      cells. CONCLUSIONS: Our findings support the possibility of inducing nestin
      expressing spheroids from purified human dermal fibroblasts in a bFGF dependent
      manner. This is important because it may be impossible to induce spheroids from
      the small pool of residual neural crest-related precursor cells found in adults.

PMID- 24855511
TI  - Human Hair Follicle Cells with the Cell Surface Marker CD34 Can Regenerate New
      Mouse Hair Follicles and Located in the Outer Root Sheath of Immunodeficient Nude
      Mice.
AB  - BACKGROUND AND OBJECTIVES: The bulge region of hair follicle has been reported as
      a putative reservoir of hair follicle stem cells. The purpose of this study was
      to compare hair follice CD34 negative (CD34-) cell with CD34 positive (CD34+)
      cell and to evaluate the ability to regenerate new hair of immunodeficient nude
      mouse. METHODS AND RESULTS: In this report, we isolated the cells with CD34,
      known as bulge-negative cell surface marker from cultured human hair follicle
      cells using by magnetic cell sorting (MACS), injected the cells to
      immunodeficient nude mouse. To determine immunological characterization, human
      hair follicle CD34+ cells and CD34- cells were assessed by flow cytometry. The
      localization of injected-CD34+ cells was assessed on formalin-fixed, paraffin
      embedded mouse skin samples by in situ hybridization technique. Our findings show
      that the human hair follicle cells with cell surface marker CD34 were located in
      the outer root sheath of nude mouse after transplantation and the cells were able
      to regenerate new hair follicle in immunodeficient nude mouse. CD34- cells also
      were able to regenerate follicles in the mouse, however, CD34+ cells were able to
      regenerate much more hair follicle than CD34- cells. CONCLUSIONS: Therefore, the
      results of this study add new insight into the investigation of CD34 stem cell
      related molecule in human hair follicles and suggest that not all human hair
      follicle stem cells reside in bulge region, but in a lager niche.

PMID- 24855513
TI  - Stem cell treatment for complicated diabetes.
AB  - BACKGROUND AND OBJECTIVES: Self renewal, homing or migration and multipotent
      differentiation are characteristics of stem cell. We studied the effect of stem
      cell treatments on diabetes complicated with impotencies using human umbilical
      cord blood stem cells (hUCBSCs). METHODS AND RESULTS: The patients who had no
      erection more than 6 months, were not responded to any medication more than 6
      months and were waiting penile prosthesis due to type 2 diabetics were
      participated and number was 5. All had normal laboratory findings except diabetes
      mellitus related one. Prepared hUCBSCs were ABO, HLA-AB, DR and sex identical to
      each patient. Total 1.5*10(7) hUCBSCs were infused into both corpus cavernosa.
      Immune suppression was not done. The blood glucose, medication dose and erection
      diary were recorded and followed for 9 months. Mean age of participants were 61
      (57~66). The blood glucose dropped from second week, and insulin or hypoglycemic
      agent doses were reduced in all patients for 6~7 months. The level of
      glycosylated hemoglobin was improved from post-treatment for 3~4 months. The
      libido was improved and morning erection was regained from 3 weeks. During the
      follow-up, one patient turned out for prosthesis, two patients were returned to
      non-erection state at 8 and 9 months and two patients maintained erections with
      medication. CONCLUSIONS: The hUCBSCs has positive effect on blood glucose and
      erectile dysfunction, although it is not sufficient. We suppose that the stem
      cell effects might be caused by combination of unknown humoral factors from
      hUCBSCs and hUCBSCs themselves.

PMID- 24855514
TI  - A SAGE View of Mesenchymal Stem Cells.
AB  - Mesenchymal stem cells (MSCs) were initially defined by their capacity to
      differentiate into connective tissue cell lineages and support hematopoiesis.
      More recently, MSCs have demonstrated some degree of therapeutic efficacy in a
      broad range of diseases including neurological and auto-immune disorders, stroke,
      diabetes, and chronic inflammatory conditions. An emerging paradigm suggests that
      MSCs alter the tissue microenvironment via paracrine signaling to induce
      angiogenesis, alter immune cell function, block inflammation, and stimulate
      growth of host cells to affect tissue repair. However, these activities appear at
      odds with the term "mesenchymal stem cell", which by definition implies a rare
      cell population that through a process of self-renewal yields progenitors that
      differentiate hierarchically into connective tissue cell types to maintain tissue
      homeostasis. Analysis of the MSC transcriptome via serial analysis of gene
      expression (SAGE) revealed that populations express a diverse array of proteins
      that are important for mesoderm specification but that also regulate various
      biochemical processes important in bone and marrow, such as angiogenesis,
      hematopoiesis, cell communication, and neural activities. Moreover, different
      classes of these regulatory proteins were found to be expressed within distinct
      sub populations of MSCs. Therefore, MSC populations appear to be more
      heterogeneous than initially envisions. Evidence is provided that this functional
      heterogeneity contributes significantly to the therapeutic effects of MSCs. 

PMID- 24855515
TI  - Clinical application of stem cells for therapeutic angiogenesis in patients with
      peripheral arterial disease.
AB  - Peripheral arterial disease (PAD) may ultimately cause to the loss of the
      affected limb due to gangrene or infection. Some patients with PAD may have
      severe coexisting diseases and diffuse involvement of their distal arteries, and
      so they are poor candidates for revascularization procedures. Angiogenesis has
      recently been suggested to be a new emerging treatment strategy for patients with
      PAD. Angiogenesis is defined as the sprouting of new capillaries from pre
      existing vascular structures; this process plays a major role in the development
      of collateral vessels in an ischemic limb. Yet, the exact mechanism of
      angiogenesis is currently poorly understood. It has been established that
      angiogenesis is initiated by hypoxia and it requires various pro-angiogenic
      factors such as vascular endothelial growth factor. Therapeutic angiogenesis is
      aimed at enhancing natural angiogenesis by the administration of the cells or
      genes that can trigger angiogenesis and this can lead to pain relief and wound
      healing by the development of collateral vessels. Most of the recent clinical
      trials have reported that stem cell therapy for promoting angiogenesis in
      patients with PAD improves the ischemic symptoms and enhances wound healing.
      However, there are several limitations to approve a standard treatment for PAD
      such as small sample size in several prevous studies, their diverse inclusion
      criteria and the lack of standard assessment methods for the safety and outcome.
      Therefore, multicenter, large-scale and randomized controlled studies are needed
      to prove the safety and efficacy of the clinically applying stem cells for
      therapeutic angiogenesis in patients with PAD. 

PMID- 24855516
TI  - Somatic cell dedifferentiation/reprogramming for regenerative medicine.
AB  - The concept of dedifferentiation or reprogramming of a somatic cell into a
      pluripotent embryonic stem cell-like cell (ES-like cell), which give rise to
      three germ layers and differentiate various cell types, opens a new era in stem
      cell biology and provides potential therapeutic modality in regenerative
      medicine. Here, we outline current dedifferentiation/reprogramming methods and
      their technical hurdles, and the safety and therapeutic applications of
      reprogrammed pluripotent stem cells in regenerative medicine. This review
      summarizes the concept and data of somatic cell nuclear transfer, fusion of
      somatic cells with ES cells, viral or non-viral transduction of pluripotency
      related genes into somatic cells, introduction of extract (or proteins) of
      pluripotent cells into somatic cells. Dedifferentiated/reprogrammed ES-like cells
      could be a perfect genetic match (autologous or tailored pluripotent stem cells)
      for future applications. Further studies regarding technical refinements as well
      as mechanistic analysis of dedifferentiation induction and re-differentiation
      into specific cell types will provide us with the substantial application of
      pluripotent stem cells to therapeutic purposes. 

PMID- 24855517
TI  - Role of Peroxisome Proliferator-Activated Receptor (PPAR)delta in Embryonic Stem
      Cell Proliferation.
AB  - The peroxisome proliferator-activated receptors (PPARs) are ligand-activated
      transcription factors that belong to the nuclear receptor family. It is well
      known that PPARs function as regulators of lipid and lipoprotein metabolism and
      glucose homeostasis, as well as influence cellular proliferation, differentiation
      and apoptosis. However, the role of the PPARs with regard to embryonic stem (ES)
      cells remains unknown. We will review the function of the PPARdelta, one of the
      three PPAR isoforms, alpha, delta (also called beta/delta), and gamma, in ES
      cells and its role in embryo development. In addition, pluripotent mouse ES cells
      can be expanded in large numbers in vitro due to the process of symmetrical self
      renewal. Here we describe how PPARdelta sustains ES cell proliferation. 

PMID- 24855519
TI  - In Vitro Differentiation and Expansion of Intrathymic T Cell Progenitors from
      Human Umbilical Cord Blood-Derived CD34(+) Cells.
AB  - BACKGROUND AND OBJECTIVES: CD4 positive cells play a central role in many lethal
      diseases, such as AIDS, cancer and autoimmunity diseases. CD4(-) commitment of
      hematopoietic stem cells involved in T cell lineage, monocyte and dendritic cells
      development. In this study, we showed that CD4 commitment out of thymus which may
      happen when hematopoietic cells undergo monocyte, dendritic cells or even earlier
      T cell progenitor differentiation. METHODS AND RESULTS: after culturing in our
      medium for more than five weeks, CD4(-)CD34(+) fraction, isolated from human
      umbilical cord blood, decreased to 1%. However, the fraction expressing CD4 went
      up to 86.5%. After CD4(+) cells were cultured in methylcellulose-based CFU
      medium, about 40 colonies/2*10(4) cells could developed. An activation of notch-1
      pathway in the freshly isolated CD34(+) cells and up-regulation of PI3K/JNK/c-Myc
      pathway may provide an explanation for the differentiation and proliferation of
      CD4(+) cells from CD34(+) hematopoietic stem cells respectively. CONCLUSIONS:
      ACD4(+) enriched population was obtained after highly purified CD34(+) cells,
      isolated from human cord blood, underwent long term culture in a feeder layer
      free culturing system. Colonigenic ability was maintained in the population of
      CD4(+) cells. This finding will be a benefit for the studies on the cell therapy
      for immune dysfunctions.

PMID- 24855518
TI  - Current status of cell therapies in stroke.
AB  - Stroke is a leading cause of death and disability in adults. Recovery after
      stroke is usually limited as there is no definite therapy to restore lost brain
      function. Cell therapy is an emerging paradigm in stroke therapy for patients
      with fixed neurologic deficits. Cell therapy for stroke may be greatly different
      from cell therapy for other disease conditions; the complexity of central nervous
      system structures and functions may limit its effectiveness. Recently, there have
      been several clinical trials of cell therapy for patients with ischemic stroke.
      In this review, the current status and limitations of cell therapy for stroke
      will be discussed. In addition, recent efforts and perspectives to improve
      therapeutic efficacy and safety of cell therapy will be summarized. 

PMID- 24855520
TI  - Characterization of Fetal Tissue-derived Mesenchymal Stem Cells.
AB  - Mesenchymal stem cells (MSCs) have unique immunologic properties that may someday
      prove useful in cell-based therapy for various degenerative diseases. Its
      potential is limited, however, by several factors, including the rarity of these
      cells and difficulty in isolating them. To evaluate their potential as new
      sources for cell therapy, we isolated MSCs from human fetal tissue (hfMSC)
      derived from spontaneous abortus (8~10 weeks) then studied their cell cycle and
      cell surface marker expression using a fluorescence-activated cell sorter (FACS),
      as well as the expression of differentiation markers using real-time polymerase
      chain reaction (RT-PCR). The hfMSCs were able to undergo PCR up to 20 times
      without displaying significant changes in morphology or expression of various
      stemness markers (Nanog and human telomerase reverse transcriptase [hAFP]),
      including germ layer markers (hNF68, alpha-cardiac actin, and hAFP). Also,
      teratomas were not seen in mice with severe combined immunodeficiency syndrome
      (SCID) that received a transplantation of hfMSCs with hTERT activity. The FACS
      analysis revealed that the majority of hfMSCs express mesenchymal markers CD13,
      CD44, CD71, CD90, CD105, CD253a, and HLA-ABC, but did not express CD31, CD34,
      CD38, CD45, and HLA-DR. Interestingly, hfMSCs derived from the cell membrane
      during early passages were negative for both HLA-ABC and HLA-DR, although HLA-ABC
      expression was detected during later passages (>20 passages). We found that
      hfMSCs could be differentiated into an osteogenic lineage; this was indicated by
      modulation of osteoblast markers specific for mRNA. We conclude that hfMSCs could
      be used as a new source of cells to treat patients with osteogenic diseases, as
      well as to understand the mechanisms of immunosuppression by MSCs. 

PMID- 24855521
TI  - Cytokine secretion profiling of human mesenchymal stem cells by antibody array.
AB  - Mesenchymal stem cells (MSCs) provide not only cell sources for connective
      tissues but also the control of hematopoiesis and immune response. A multitude of
      cytokines and growth factors secreted from MSCs are known to confer such
      multifunctional functionality, but their overall spectrum and the respective
      expression strength have not been thoroughly illustrated. In this study, we have
      obtained the comprehensive cytokine secretion profile of human bone marrow (BM)
      derived MSCs, with the use of an antibody array recognizing 120 cytokines and
      chemokines. The array membrane incubated with the secretion media of the cells
      featured a predominant hybridization signal for IL-6 and moderately elevated
      signals for IL-8, TIMP-2, MCP-1, VEGF and OPG. This cytokine secretion profile
      was found to be common to all cell lines from three different donors, and also
      similar but not identical to that of umbilical cord blood-derived cells,
      suggesting that the trophic nature of the MSCs might depend slightly on the cell
      origin but not on individuality of the donors. Our results here may provide the
      molecular basis for further studies on MSC-assisted biological processes, such as
      connective tissue homeostasis, hematopoiesis and immune modulation. 

PMID- 24855522
TI  - Effect of Culture Conditions on Reference Genes Expression in Placenta-derived
      Stem Cells.
AB  - BACKGROUND AND OBJECTIVES: Normalization with valid reference genes is crucial
      for gene expression analysis with quantitative real-time reverse transcription
      PCR (qRT-PCR). This is especially relevant when stem cells are investigated with
      respect to gene expression in the differentiation process. Due to the plasticity
      of the stem cells, the variation of reference gene expression may cause
      misinterpretation of the target gene expression. METHODS AND RESULTS: In this
      study, we investigated the gene expression stability of commonly used 32
      reference genes in placenta-derived stem cells, which were cultured with or
      without exogenous epidermal growth factor. The influence of unstable reference
      gene expression on the data interpretation was also demonstrated with stem cell
      marker gene expressions on the placenta-derived stem cells. Statistical
      validation analysis of reference genes revealed the stability of each gene.
      Commonly used beta-actin, 18S and GAPDH expression were relatively instable. The
      cell cycle relating house keeping genes, PPIA, POLR2A, and POP4 were most stable
      in the compared culture conditions. Reference genes were divided into the
      following three groups and statistically analyzed; 1) unstable genes, 2) stable
      genes, and 3) commonly used genes. The results indicate that the interpretation
      of the experiments was significantly different depending on the stability of the
      reference genes. CONCLUSIONS: In the stem cell experiments, even minor
      differences in the culture conditions influenced the expression of reference
      genes. Thus, the identification of valid reference genes must be determined at
      each experimental setting. We recommend performing a stepwise screening process
      to determine valid reference genes.

PMID- 24855523
TI  - Clonal Mature Adipocyte Production of Proliferative-competent Daughter Cells
      Requires Lipid Export Prior to Cell Division.
AB  - BACKGROUND AND OBJECTIVES: Numerous in vitro observations have been published to
      show that mature adipocytes may resume proliferation and begin to populate the
      adipofibroblast fraction or form other cell types. METHODS AND RESULTS: In the
      present study, we evaluated clonal cultures of mature pig-derived adipocytes as
      they began to reestablish their ability to divide. The lipid contained within the
      cytoplasm was either moved to the apical ends of the cell, or large droplets were
      physically extruded from the cell. In the latter case, we ascertained that the
      cell lipid droplet was handled in a different manner to that by beef-derived
      adipocytes as described in other published studies. CONCLUSIONS: Pig-derived
      adipocytes expel large amounts of lipid directly into the medium environment
      prior to becoming capable of cell division, rather than retaining all lipids like
      the beef cells. This difference in lipid handling and trafficking may be a novel
      mechanism in adipocyte resumption of proliferation.

PMID- 24855524
TI  - Cord blood: from garbage to life-saving source.

PMID- 24855525
TI  - Non-hematopoietic stem cells in umbilical cord blood.
AB  - Allogeneic umbilical cord blood (UCB) transplantation has been used to treat a
      variety of malignant and non-malignant diseases. Recent studies show convincing
      evidence that UCB contains not only hematopoietic progenitors, but also several
      types of stem and progenitor cells providing a high proliferative capacity and a
      variety of differentiation potentials. UCB-derived cells offer multiple
      advantages over adult stem cells from other sources like bone marrow (BM),
      because UCB can be collected without painful procedure, easily available in
      virtually unlimited supply, and has not been exposed to immunologic challenge. In
      addition, cord blood transplantation is now an established field with great
      potential and no serious ethical issue by establishment of public UCB banks
      throughout the world. Therefore UCB-derived non-hematopoietic stem cells may
      provide an attractive cell source for tissue repair and regeneration. It is
      generally accepted that UCB contains endothelial progenitor cells (EPC),
      mesenchymal stromal cells (MSC), unrestricted somatic stem cells (USSC), very
      small embryonic-like stem cells (VSEL), multilineage progenitor cells (MLPC), and
      neuronal progenitor cells. This review focuses on biological properties of these
      non-hematopoietic stem/progenitor cells derived from human UCB and their
      potential use in cell based therapies. 

PMID- 24855526
TI  - Usefulness of umbilical cord blood cells in era of hematopoiesis research.
AB  - Although worldwide experience with umbilical cord blood (UCB) transplantation is
      still relatively limited, clinical experience with UCB transplantation is
      encouraging. The use of UCB for hematopoietic stem cell transplantation (HSCT)
      has advantages and disadvantages. Among the advantages are rapid availability,
      ability to more rapidly schedule the transplant as the UCB units are stored and
      ready for use, the apparent reduced need for an exact human leukocyte antigen
      (HLA) match, and induction of a less severe graft versus host disease (GVHD)
      compared with bone marrow. The major limitation of reduced numbers of
      hematopoietic stem cells (HSC) in UCB is being addressed by basic research. It is
      promising that potential improvements in engraftment efficiency without increased
      stem cell numbers or actual increased stem cell numbers through dual UCB
      transplant or ex-vivo expansion might lead to improved treatment approaches.
      However, its therapeutic potential extends beyond the hematopoietic component
      suggesting regenerative potential in solid organs as well. Many different stem
      and progenitor cell populations have been postulated with potential ranging from
      embryonic like to lineage-committed progenitor cells. UCB derived MSCs have the
      differentiation capacity and also the therapeutic potential with regard to
      regenerative medicine, stromal support, immune modulation and gene therapy.
      Therefore, further advances are eagerly anticipated. 

PMID- 24855527
TI  - Liver stem cells derived from the bone marrow and umbilical cord blood.

PMID- 24855528
TI  - Stem Cells Transplantation and Huntington's Disease.
AB  - Huntington's disease (HD) is a progressive and devastating neurodegenerative
      disorder that results in movement abnormalities, cognitive impairments, dementia,
      and affective disturbances. As no proven medical therapy for this genetic disease
      is currently available, symptoms mitigation is the primary treatment for HD. Stem
      cells can play an important role in cell therapy therapeutic strategies to
      replace dysfunctional or dying cells in HD. Here, we present a brief overview of
      the current state of stem cells therapy and of the results obtained in animal
      models of HD, and discuss neuro-protective approaches that utilize stem cells
      derived paracrine factors. 

PMID- 24855529
TI  - Cancer stem cells and their mechanism of chemo-radiation resistance.
AB  - The advent of cancer stem cell (CSC) hypothesis has revolutionized the cancer
      biology community's thinking in explaining the notorious resistance of cancer to
      conventional chemo- and radiotherapies. The hypothesis states that the CSCs are a
      subpopulation within the tumor endowed with superior resistance and with the
      exclusive ability to self-renew, differentiate into diverse type of progeny
      cancer cells, and initiate tumor. Here, we review recent literature that seek out
      to explain such resistance of CSCs. Signaling pathways involved in the regulation
      of proliferation and differentiation of stem cells (e.g. Notch, Hh, and Wnt) and
      efficient ABC transporter systems and DNA damage response machineries are
      starting to be identified as the means by which CSCs out-survive their non-CSC
      neighbors after conventional anti-cancer treatments. Direct links between
      receptor tyrosine kinase pathways and CSCs are also starting to emerge as well.
      Lastly, a promising relationship between epithelial-mesenchymal transition and
      CSCs is discussed. Though the precise resistance pathway of CSCs is not yet fully
      elucidated, the various mechanisms highlighted here provide promise for better
      fundamental understanding of CSCs and the subsequent development of a more
      effective CSC-targeting therapeutic in the foreseeable future. 

PMID- 24855530
TI  - Adult stem cells as a renewable source of insulin-producing cells.
AB  - Diabetes mellitus is a metabolic disorder resulting from an inadequate mass of
      insulin-producing pancreatic beta cells. The replacement or restoration of
      damaged beta cells would be considered the optimal therapeutic options. Islet
      transplantation seems to be a promising approach for replacement therapy;
      however, the main obstacle is the shortage of organ donors. As mature beta cells
      have been shown to be difficult to expand in vitro, regeneration of beta cells
      from embryonic or adult stem cells or pancreatic progenitor cells is an
      attractive method to restore the islet cell mass. So far, multiple studies using
      various strategies have shown direct differentiation of stem and progenitor cells
      toward insulin-producing cells. The important issue to be solved is how to
      differentiate these cells into mature functional insulin-producing cells. Further
      research is required to understand how endogenous beta cells differentiate and to
      develop methods to regenerate enough functional beta cells for clinically
      applicable therapies for diabetes. 

PMID- 24855531
TI  - Adult stem cell therapy for autoimmune disease.
AB  - Many studies of autologous hematopoietic stem cell transplantation (HSCT) and
      allogeneic HSCT have been conducted for autoimmune disease in various animal
      models. Because of the substantial risk of morbidity and mortality associated
      with allogeneic bone marrow transplantation, autologous transplants justified
      trying this approach in patient with severe autoimmune disease who were
      refractory to current treatments. Remission was achieved in some of the patients
      and some of them relapsed. Recently, many in vitro studies have reported that
      mesenchymal stem cells (MSC) have immunomodulatory properties and
      immunosuppressive effects on MHC-mismatched lymphocytes proliferation by
      inhibiting naive, memory and activated T cells, B cell, NK cells and dendritic
      cells. In addition, adipose tissue-derived MSC (AT-MSC) are becoming an
      alternative source of MSC for therapeutic applications because adipose tissues
      are abundant, easily accessible, easily obtainable with little patient discomfort
      and large amounts of AT-MSC can be easily obtained. A large body of in vitro
      research has shown that AT-MSC have same or similar immunomodulatory effects with
      bone marrow derived MSC. Drawing on this finding, the increasing numbers of
      researchers have turned on their attention to preclinical studies on AT-MSC. As
      this new path of research evolves with subsequent reports, MSC would make a
      significant contribution to stem cell therapy or combination therapy for
      ameliorating symptoms and curing autoimmune disease. By searching and studying
      the appropriate therapeutic gene, the therapeutic gene transfected stem cell
      therapy will be able to acquire the synergy effect and the combined advantage of
      gene therapy and stem cell therapy. 

PMID- 24855532
TI  - The Primary Study of CD90(+)CD34(-)and Sca-1(+) Stem Cells Mobilized by EPO Plus
      G-CSF in Mice.
AB  - To investigate effects of recombinant human erythropoietin (rhEPO) plus
      recombinant human granulocyte colony stimulating factor (rhG-CSF) on mobilization
      of CD90(+)CD34(-) and Sca-1(+) stem cells in mice. rhEPO 1000 IU.kg(-1).d(-1) per
      mice alone or plus rhG-CSF 250 MUg.kg(-1).d-1(-1)per mice was administered to
      mice for five days, the peripheral blood was collected at 6 hours, 1, 3,5 and 7
      days after the last administration. The number of white blood cells (WBC) and
      mononuclear cells (MNC) was counted. The level of CD34, CD90 and Sca-1 mRNA were
      detected by reverse transcription-polymerase chain reaction (RT-PCR).The
      expressions of CD90(+)CD34(-) in absolute nuclear cells of peripheral blood was
      detected by flow cytometry. The results indicate that compared to mobilizing by
      rhG-CSF, rhEPO or plus rhG-CSF did not significantly enhance the number of WBC
      and MNC, on the fifth and the seventh day after the last administration, both the
      expression of CD34,CD90 and Sca-1 mRNA and the proportion of CD90(+)CD34(-) cells
      dramatically raised in rhEPO or in addition to rhG-CSF groups. We conclude that
      rhEPO or plus rhG-CSF had a strong capacity of mobilization of stem cells. The
      alteration of expression of CD34, CD90 and Sca-1 mRNA after the administration of
      rhEPO or combined with rhG-CSF indicated that this agents might potentially alter
      the peripheral blood graft content. 

PMID- 24855533
TI  - Adipose Tissue is A Better Source of Immature Non-Hematopoietic Cells than Bone
      Marrow.
AB  - Adipose tissue (AT) is an alternative source of the adult stem cells that can
      also be harvested from bone marrow (BM). Cultured AT-derived stem cells (ASCs)
      have been well characterized by many groups. However, non-cultured ASCs remain to
      be characterized. Hoechst 33342 dye efflux is a characteristic that is common to
      stem cells, as well as chemotherapy-resistant cancer cells. Thus, we compared the
      Hoechst 33342-stained side population (SP) cells in murine adipose-tissue (AT-SP
      cells) to the SP cells from murine bone marrow (BM-SP cells). The AT-SP cells
      were detected much more frequently in the 22 AT samples that were tested
      (0.42~6.00%, mean 2.57%) than the BM-SP cells were detected in the 6 BM samples
      (0.02~0.36%, mean 0.12%). After Hoechst staining, SP cells were analyzed by
      fluorescence-activated cell sorting (FACS) and electron micrograms. FACS analysis
      revealed that the AT-SP cells were CD44-, CD45-, CD45R+, Sca-1+/- and c-kit-,
      while the BM-SP cells were CD44-, CD45+/-, CD45R-, Sca-1+ and c-kit+. This
      indicates that the AT-SP cells differ phenotypically from the BM-SP cells.
      Electron microscopic analysis revealed that the AT-SP cells are small cells with
      a diameter of about 5 um. Some of the BM-SP cells had granules, similar to
      eosinophils or basophils, whereas the AT-SP cells had fewer organelles and a
      higher N/C ratio than the BM-SP cells. This suggests that the AT-SP cells are
      considerably more immature than the BM-SP cells. Thus, it appears that AT is a
      better source of immature non-hematopoietic cells than BM. 

PMID- 24855534
TI  - Thromoboagiitis Obliterans (TAO).
AB  - Thromboangiitis obliterans (TAO) is nonatherosclerotic inflammatory disease of
      the peripheral blood vessels, and TAO affects the small and medium sized vessels
      of the extremities. TAO is mainly seen in young males who smoke, and smoking is
      strongly associated with the disease course and progression. The diagnosis is
      made on the basis of the history, the physical examination and the clinical
      diagnostic criteria. As the bedrock for treating patients with TAO, absolute
      abstinence from tobacco is most important factor, and patients with TAO are
      usually managed conservatively. Surgical bypass or endovascular therapy is
      usually not possible for patients with TAO because of the diffuse segmental
      involvement and the distal nature of the disease. Therefore, stem cell therapy is
      considered to be a novel therapeutic modality for treating patients with TAO and
      who are not eligible for conventional revascularization therapies. In this paper,
      I have summarized the recent knowledge about TAO and I have reviewed the recent
      studies that have focused on the treatment of TAO. 

PMID- 24855535
TI  - Cell therapy for myocardial infarction.
AB  - Ischemic heart disease, particularly acute myocardial infarction (MI), is the
      worldwide health care problem and the leading cause of morbidity and mortality.
      The fundamental treatment of MI remains a major unmet medical need. Although
      recent tremendous advances have been made in the treatment for acute MI such as
      percutaneous coronary intervention (PCI) and medical and surgical therapies,
      myocardial cell loss after ischemia and subsequent, adverse cardiac remodeling
      and heart failure are demanding for new therapeutic strategy. Since the first
      experimental studies of adult stem cell therapy into the ischemic heart were
      performed in the early 1990s, the identification and potential application of
      stem and/or progenitor cells has triggered attempts to regenerate damaged heart
      tissue and cell-based therapy is a promising option for treatment of MI. In this
      review, we would like to discuss the pathogenesis of acute MI, current standard
      treatments and their limitation, clinical results of recent stem or progenitor
      cell therapy which have shown a favorable safety profile with modest improvement
      in cardiac function, and putative mechanisms of benefits. 

PMID- 24855536
TI  - Adult stem cell therapy for periodontal disease.
AB  - Periodontal disease is a major cause of tooth loss and characterized by
      inflammation of tooth-supporting structures. Recently, the association between
      periodontal disease and other health problems has been reported, the importance
      of treating periodontal disease for general health is more emphasized. The
      ultimate goal of periodontal therapy is regeneration of damaged periodontal
      tissues. The development of adult stem cell research enables to improve the cell
      based tissue engineering for periodontal regeneration. In this review, we present
      the results of experimental pre-clinical studies and a brief overview of the
      current state of stem cells therapy for periodontal diseases. 

PMID- 24855537
TI  - Implication of cord blood for cell-based therapy in refractory childhood
      diseases.
AB  - Since cord blood (CB) contains hematopoietic stem cells as well as a mixture of
      multipotent stem cells, CB has the ability to give rise to hematopoietic,
      epithelial, endothelial and neural tissues. Recently, the application of cell
      based therapy using CB has expanded its clinical utility, particularly, by using
      autologous CB in children with refractory diseases. This review focuses clinical
      and pre-clinical application of CB cell-based therapy for inherited metabolic
      diseases as well as tissue regenerations in neonatal hypoxic-ischemic
      encephalopathy, cerebral palsy, and juvenile diabetes. 

PMID- 24855538
TI  - Stem cell therapy for dermal wound healing.
AB  - The use of cellular therapy in the treatment of dermal wounds is currently an
      active area of investigation. Multipotent adult stem cells are an attractive
      choice for cell therapy because they have a large proliferative potential, the
      ability to differentiate into different cell types and produce a variety
      cytokines and growth factors important to wound healing. This review focused on
      the roles of adult stem cells such as endothelial progenitor cells, bone marrow
      and adipose-derived mesenchymal stem cells, during dermal wound healing process
      and their therapeutic potentials for the treatment of chronic wounds, which
      remain a major clinical problem, especially in diabetic patients. 

PMID- 24855539
TI  - The cord blood separation league table: a comparison of the major clinical grade
      harvesting techniques for cord blood stem cells.
AB  - BACKGROUND AND OBJECTIVES: Well over 1 million Umbilical Cord Blood units (UCB)
      have been stored globally in the last 10 years. Already, over 20,000 transplants
      been performed using UCB for haematopoietic reconstitution alone, now this
      potential is joined by regenerative medicine. However, more needs to be known
      about processing of this stem cell source for it to reach full potential. METHODS
      AND RESULTS: IN THIS STUDY WE EVALUATED FIVE SEPARATION METHODS: plasma
      depletion, density gradient, Hetastarch, a novel method known as PrepaCyte-CB and
      an automated centrifugal machine. Sepax gives the highest recovery of nucleated
      cells, an average of 78.8% (SD+/-21.36). When looking at CD34+ haematopoietic
      stem cells PrepaCyte-CB provided the greatest recovery at 74.47% (SD+/-8.89). For
      volume reduction density gradient was the most effective leaving 0.03*10(6)
      RBC/ml, 8 times more efficient than its nearest competitor PrepaCyte-CB (p<0.05).
      Finally PrepaCyte-CB processing left samples with the highest clonogenic
      potential after processing and more significantly after cryopreservation: 9.23
      CFU/10(8) cells (SD+/-2.33), 1.5 fold more effective than its nearest rival Sepax
      (p<0.05). CONCLUSIONS: PrepaCyte-CB was the most flexible method; the only
      processing type unaffected by volume. Results indicate that processing choice is
      important depending on your final intended use.

PMID- 24855540
TI  - Timing of the cell cycle exit of differentiating hippocampal neural stem cells.
AB  - Neural stem cells contribute to mammalian brain tissue turnover in specific
      locations throughout life. Differentiation of stem cells is associated with
      terminal mitosis and cell cycle exit, but it is unclear how the timing and
      signaling of these are interlinked. Here, we have investigated the cell cycle
      exit characteristics in comparison with morphological changes during hippocampal
      stem cell differentiation in an adult mammalian cell line. Our results suggest
      that the cell-specific gene pathway induction is fast and robust and takes place
      in one day, whereas the cell cycle exit machinery is slower and takes several
      days to fully execute. The hippocampal differentiation is associated with
      epigenetic changes, such as Ezh2 down regulation and histone methylation. A small
      percentage of stem cells is able to resist differentiation-induced terminal
      mitosis for weeks in culture, and can be reverted to proliferation by re-adding
      the mitotic growth factors. 

PMID- 24855541
TI  - An animal model of chronic aplastic bone marrow failure following pesticide
      exposure in mice.
AB  - The wide use of pesticides for agriculture, domestic and industrial purposes and
      evaluation of their subsequent effect is of major concern for public health.
      Human exposure to these contaminants especially bone marrow with its rapidly
      renewing cell population is one of the most sensitive tissues to these toxic
      agents represents a risk for the immune system leading to the onset of different
      pathologies. In this experimental protocol we have developed a mouse model of
      pesticide(s) induced hypoplastic/aplastic marrow failure to study quantitative
      changes in the bone marrow hematopoietic stem cell (BMHSC) population through
      flowcytometric analysis, defects in the stromal microenvironment through short
      term adherent cell colony (STACC) forming assay and immune functional capacity of
      the bone marrow derived cells through cell mediated immune (CMI) parameter study.
      A time course dependent analysis for consecutive 90 days were performed to
      monitor the associated changes in the marrow's physiology after 30(th), 60(th)
      and 90(th) days of chronic pesticide exposure. The peripheral blood showed
      maximum lowering of the blood cell count after 90 days which actually reflected
      the bone marrow scenario. Severe depression of BMHSC population, immune profile
      of the bone marrow derived cells and reduction of adherent cell colonies pointed
      towards an essentially empty and hypoplastic marrow condition that resembled the
      disease aplastic anemia. The changes were accompanied by splenomegaly and splenic
      erythroid hyperplasia. In conclusion, this animal model allowed us a better
      understanding of clinico-biological findings of the disease aplastic anemia
      following toxic exposure to the pesticide(s) used for agricultural and industrial
      purposes. 

PMID- 24855542
TI  - The Effect of Nutritional Supplements on Muscle-Derived Stem Cells in vitro.
AB  - Postnatal muscle stem cells, recognized as myogenic satellite cells, were
      isolated from sheep skeletal muscle and used in these experiments. Forty-one
      different metabolic compounds that are commonly found in commercially-available
      oral supplements were exposed to primary muscle stem cell cultures, in an effort
      to ascertain whether any one compound could alter satellite cell proliferation or
      differentiation (a first step towards elucidating the metabolomics or
      nutrigenomics of these stem cells). These compounds included energetic moieties,
      amino acid analogs, fatty acids and analogs including different forms of
      conjugated linoleic acid, minerals and mineral conjugates, insect hormones,
      caffeine, plant extracts, and extracts from over-the-counter supplements, and
      were obtained by key manufacturers in a form that would be commercially
      available. The compounds were sterilized and then exposed to myogenic satellite
      cell cultures at different levels (ranging from toxic to physiologic) to
      ascertain if there would be an effect. The results suggested that exposure of
      satellite cells to only a few compounds resulted in any measurable effect(s). Ten
      compounds elicited increases in proliferation, and four compounds promoted
      increases in differentiation. These results suggest avenues for the exploration
      of enhancing muscle stem cell activity of interest for muscle wasting disorders,
      sarcopenia of aging and physical performance. 

PMID- 24855543
TI  - Roles of spheroid formation of hepatocytes in liver tissue engineering.
AB  - The liver plays an important role in a broad spectrum of physiological functions
      and detoxifies endogenous and exogenous substances. The liver failure is
      associated with a high risk of mortality because it is one of important organs in
      our body. Various bioartificial liver (BAL) systems have been used for clinical
      trials as a bridge for liver transplantations in patients with liver failure.
      Long term and stable liver-specific functions of hepatocytes in the development
      of BAL support systems should be considered. Spheroid formation of hepatocytes
      enhances liver-specific functions. In this review, hepatocyte spheroid formation
      methods such as galactose density, topology of extracellular matrix, micro
      molding technique, hanging-drop culture, non-adhesive surface, positive charged
      surface, spinner culture, rocked technique, medium component, external forces,
      coculture system and polymeric nanospheres are explained for enhancing liver
      specific functions. 

PMID- 24855544
TI  - Application of ultrasound stimulation in bone tissue engineering.
AB  - Many studies have been investigated on the effects of the low-intensity pulsed
      ultrasound (LIPUS) on bone healing, acceleration of bone mineralization and
      regeneration. Many researchers have focused on a more comprehensive understanding
      of the biological mechanism of the osteoblast by LIPUS because the osteoblast is
      an important cell in bone formation. The effects of LIPUS on the proliferation,
      gene expression of Runx2, Msx2, Dlx5, and AJ18, and the second messenger
      signaling of osteoblast were reported. Various parameters of LIPUS, such as
      intensity, frequency, duration and topology, were investigated to find
      appropriate conditions in osteoblast. Less than 120 mW/cm(2) of intensity and 1-3
      MHz of frequency were considered good condition for regeneration of bone tissue.
      Increased osteoblast cells and higher mineralized nodule formation explain the
      enhancement of proliferation by LIPUS. In addition, LIPUS affects on
      differentiation of osteoblast cells, which is shown by increased ALPase, and
      transcriptional factors, Runx2. Ultrasound stimulates PEG2 and COX-2 in
      osteoblast, and the signals accelerates the bone regeneration in tissue
      engineering. 

PMID- 24855545
TI  - Modulation of stem cell differentiation with biomaterials.
AB  - Differentiation of stem cells can be controlled with interactions with
      microenvironments of the stem cells. The interactions contain various signals
      including soluble growth factor signal, cell adhesion signal, and mechanical
      signal, which can modulate differentiation of stem cells. Biomaterials can
      provide these types of signals to induce desirable cellular differentiation.
      Biomaterials can deliver soluble growth factors locally to stem cells at a
      controlled rate for a long period. Stem cell adhesion to specific adhesion
      molecules presented by biomaterials can induce specific differentiation.
      Mechanical signals can be delivered to stem cells seeded onto biomaterial
      scaffolds. These approaches would be invaluable for direction of stem cell
      differentiation and in vivo tissue regeneration using stem cells. 

PMID- 24855546
TI  - Solid Free-form Fabrication Technology and Its Application to Bone Tissue
      Engineering.
AB  - The development of scaffolds for use in cell-based therapies to repair damaged
      bone tissue has become a critical component in the field of bone tissue
      engineering. However, design of scaffolds using conventional fabrication
      techniques has limited further advancement, due to a lack of the required
      precision and reproducibility. To overcome these constraints, bone tissue
      engineers have focused on solid free-form fabrication (SFF) techniques to
      generate porous, fully interconnected scaffolds for bone tissue engineering
      applications. This paper reviews the potential application of SFF fabrication
      technologies for bone tissue engineering with respect to scaffold fabrication. In
      the near future, bone scaffolds made using SFF apparatus should become effective
      therapies for bone defects. 

PMID- 24855547
TI  - Stem Cell-assisted Approaches for Cartilage Tissue Engineering.
AB  - The regeneration of damaged articular cartilage remains challenging due to its
      poor intrinsic capacity for repair. Tissue engineering of articular cartilage is
      believed to overcome the current limitations of surgical treatment by offering
      functional regeneration in the defect region. Selection of proper cell sources
      and ECM-based scaffolds, and incorporation of growth factors or mechanical
      stimuli are of primary importance to successfully produce artificial cartilage
      for tissue repair. When designing materials for cartilage tissue engineering,
      biodegradability and biocompatibility are the key factors in selecting material
      candidates, for either synthetic or natural polymers. The unique environment of
      cartilage makes it suitable to use a hydrogel with high water content in the
      cross-linked or thermosensitive (injectable) form. Moreover, design of composite
      scaffolds from two polymers with complementary physicochemical and biological
      properties has been explored to provide residing chondrocytes with a combination
      of the merits that each component contributes. 

PMID- 24855548
TI  - Umbilical cord matrix derived mesenchymal stem cells can change the cord blood
      transplant scenario.
AB  - BACKGROUND AND OBJECTIVES: The field of Umbilical cord blood (UCB) hematopoietic
      stem cell transplantation has had an amazing run since 1988. UCB is being
      increasing used in related and unrelated transplant settings. A major hurdle,
      however, in the use of UCB is its low cell dose, which is largely responsible for
      an elevated risk of graft failure and significantly delayed neutrophils and
      platelet engraftment. Strategies to increase CD34(+) HSC/HPC dose are under
      development as a direct correlation has been shown between these counts and time
      for engraftment. One strategy includes the ex vivo expansion of UCB derived
      CD34(+) cells. METHODS AND RESULTS: We show that the umbilical cord derived
      mesenchymal stem cells (UCMSCs) can be used as supporting cells for ex vivo
      expansion of CD34(+) cells using low concentrations of cytokine cocktail. The
      UCMSCs release the cytokines required for maintenance and proliferation of
      CD34(+) cells in the ex vivo culture conditions. More than 25 fold increase in
      total nucleated cell count (TNC) and more than 20 fold increase in CD34(+) cell
      count has been obtained using this co-culture system. CONCLUSIONS: UCMSCs from
      both, autologous and allogeneic origin can be used for expansion of UCB derived
      CD34(+) cells. The ease of availability and immunoprivileged nature of UCMSCs
      further holds promise in their use in an allogeneic transplant setting.

PMID- 24855549
TI  - Derivation, expansion and characterization of clinical grade mesenchymal stem
      cells from umbilical cord matrix using cord blood serum.
AB  - BACKGROUND AND OBJECTIVES: With increasing use of mesenchymal stem cells (MSCs)
      in regenerative medicine, there is greater awareness towards the need to have
      clinical grade products. The bovine media currently used allow good expansion to
      give large number of MSCs of the right quality. This report brings the
      significance of using cord blood serum (CBS) in the derivation of MSCs from
      umbilical cord matrix, to help its clinical applicability. METHODS AND RESULTS:
      MSCs isolated from the cord by explant cultures were expanded and characterized
      by flow cytometry. Cord blood serum while helping expansion, has the ability to
      preserve the immunophenotype and differentiation potential of the MSCs derived
      from the umbilical cords. CONCLUSIONS: Our results suggest that MSCs derived and
      expanded in cord blood serum are better suited for clinical applications.

PMID- 24855550
TI  - Notch and hedgehog signaling cooperate to maintain self-renewal of human
      embryonic stem cells exposed to low oxygen concentration.
AB  - BACKGROUND AND OBJECTIVES: Expansion and maintenance of human embryonic stem
      cells (hESCs) in undifferentiated state is influenced by complex signals in the
      microenvironment, including those contingent upon oxygen availability. Responses
      mediated by Notch and Hedgehog (Hh) have essential role in the growth and
      maintenance of hESCs, therefore this study examined their effect on the self
      renewal of hESCs exposed to low oxygen. METHODS AND RESULTS: Using potent
      antagonists gamma-secretase inhibitor and cyclopamine, we inhibited Notch and Hh
      pathways, respectively, in the CLS1 hESC line expanded continuously in a hypoxic
      atmosphere of 5% oxygen. Immunohistochemical staining and protein assays revealed
      loss of Oct4 and gain of stage-specific embryonic antigen 1 (SSEA1) markers in
      the inhibited cells. Semiquantitative real-time RT-PCR, and bromodeoxyuridine and
      thymidine incorporation assays demonstrated low Oct4 and Nanog mRNA expression,
      and decreased DNA synthesis, respectively, resulting from the block of each of
      the pathways. The loss increased significantly with co-inhibition of both
      pathways. Importantly, Notch and Hh downstream targets, including Hes1, Hey1,
      GIi1, and Ptc1, were surprisingly suppressed not only by the pathway-specific but
      also the unrelated inhibitor. CONCLUSIONS: These findings demonstrate
      complementary effect of Notch and Hh signaling in hypoxia enhanced maintenance of
      hESCs.

PMID- 24855551
TI  - Cell sheet injection as a technique of osteogenic supply.
AB  - We previously reported a new cell transplantation method utilizing injections of
      mesenchymal stem cell (MSC) sheets that have osteogenic potential. After
      subcutaneous transplantation without any scaffold, the sheet demonstrated in vivo
      bone formation. In the present study, we transplanted such sheets by injection
      into implanted ceramics and assessed whether the injectable MSC sheets could
      stimulate osteogenic integration of the ceramics. To fabricate MSC sheets, bone
      marrow cells cultured from femur shafts of 7-week-old rats were subcultured in
      regular 10-cm dishes containing dexamethasone and ascorbic acid phosphate until
      confluent. Each cell sheet was then lifted using a scraper. Porous beta
      tricalcium phosphate (beta-TCP) disks (5 mm Phi*2 mm) were transplanted
      subcutaneously into the backs of the rats. Immediately following implantation,
      the sheets were injected around the disks via a 16G needle (immediate group).
      Cell sheets were also injected into the remaining implanted disks 1 week after
      disk implantation (1-wk group). Four weeks following sheet injection, radiography
      and histology revealed calcification and bone tissue around the harvested disks
      of the immediate group (eight disks exhibited bone formation/eight implanted
      disks), whereas calcification and bone tissue were observed in 50% of the samples
      in the 1-wk group (four disks exhibited bone formation/eight implanted disks).
      The present study indicates that injected cell sheets can supply osteogenic
      potential to implanted ceramics. Owing to the usage of a needle for cell sheet
      transplantation, such an injection method can be applied as a minimally invasive
      technique of osteogenic supply to implanted ceramics. 

PMID- 24855552
TI  - Effects of supermagnetic iron oxide labeling on the major functional properties
      of human mesenchymal stem cells from multiple sclerosis patients.
AB  - BACKGROUND AND OBJECTIVES: In the last few years, treatment protocols using
      mesenchymal stem cells (MSC) in various experimental models and human diseases
      have been investigated. MSCs are on the focus of stem cell research, since they
      are considered as a type of adult stem cells with low toxicity and acceptable
      side effects profile and they can be administered autologously. In addition
      several studies have revealed significant immunomodulatory properties of MSCs and
      a potential for transdifferentiation, including neural differentiation, both in
      vivo and in vitro. Magnetic resonance imaging (MRI) is a non-invasive technique
      that can be used to track labeled cells and evaluate their migration ability in
      various clinical settings. METHODS AND RESULTS: In this study we investigated
      whether such labeling of MSCs with the commercially used para-magnetic material,
      Feridex, has any negative effect on the above mentioned functional properties of
      MSCs. We labeled human mesenchymal stem cells (hMSC) with poly-L-lysine coated
      Feridex((r)) and evaluated their cellular differentiation and immunomodulatory
      properties, in vitro. In comparison with unlabeled cells, labeled hMSC exhibited
      normal adipogenic and osteogenic differentiation, but decreased chondrogenic
      differentiation. Regarding neural differentiation, labeled and unlabeled cells
      were similar in their ability to express neural-like and glial like surface
      proteins. Finally, both labeled and unlabeled MSCs exhibited a dose-dependent,
      significant blocking effect on the proliferation of healthy donors lymphocytes
      following mitogen stimulation. CONCLUSIONS: These findings indicate that labeling
      with Feridex does not affect the immunomodulatory, nor the neural
      transdifferentiation potential of MScs and therefore, Feridex may be used for the
      tracking of this type of stem cells in clinical applications, without
      compromising their major functional properties.

PMID- 24855553
TI  - Migration of human umbilical cord blood cells into rat liver.
AB  - BACKGROUND AND OBJECTIVES: Cell therapy provides an effective strategy for the
      treatment of an impaired liver. Human umbilical cord blood progenitor cells have
      the potential to differentiate into hepatocytes. Progenitor cells transplanted
      into the spleen could migrate directly into the liver through portal circulation.
      To track migration of human umbilical cord blood progenitor cells in cirrhotic
      rat liver after intrasplenic transplantation and to prove the possibility similar
      behavior of human umbilical cord blood nucleated cells in humans. METHODS AND
      RESULTS: Umbilical cord blood samples from full-term deliveries will be collected
      after obtaining an informed consent from the mother. The collection procedure
      will be conducted after completion of delivery and will not interfere with the
      normal obstetric procedures. Adult male Sprague Dawley rats were subjected to
      liver cirrhosis by intraperitoneal injection of thioacetamide. Cirrhotic rats
      were treated with human umbilical cord blood nucleated cells by intra-splenic
      transplantation. Migration of intrasplenic transplanted human umbilical cord
      blood cells to the liver was successfully documented with Immunohistochemistry.
      The liver and spleen from recipient animals were removed. Histopathological and
      immunohistochemical analysis were performed 20 weeks after intrasplenic injection
      of the cells. Intrasplenically injected cells migrate to the liver of recipient
      animals. CONCLUSIONS: Human cord blood nucleated cells have the potential to
      differentiate into hepatocytes and substantially improve the histology and
      function of the cirrhotic liver in rats. Relocation into liver after intrasplenic
      transplantation could be detected by immunohistochemistry. Transdifferentiated
      cells could be efficiently stained with antihuman hepatocytes.

PMID- 24855554
TI  - Reversal of Hepatic Fibrosis by Human CD34(+) Stem/Progenitor Cell
      Transplantation in Rats.
AB  - Human umbilical cord blood (UCB) cells have many advantages as grafts for cell
      transplantation. Here, we transplant UCB cells into injured liver fibrosis,
      investigated the hepatic potential of UCB cells both in vitro and in vivo. a CCl4
      rat model with liver fibrosis was prepared. Human (UCB) CD34(+) stem cell was
      separated with MACS (magnetic cell sorting). Cells were cultured with and without
      hepatic differentiation medium. Rats were divided into 3 groups; group (1):
      control healthy, group (2): CCl4 injected rats and group 3: CCl4/CD34(+)injected
      rats with human differentiated and undifferentiated cells through intrahepatic
      (IH) and intravenous (IV) routes. A significant elevation was detected in serum
      albumin in CCl4/CD34(+) compared to the CCl4 group (p<0.001). Serum ALT, had a
      significant decrease of its level after administration of stem cells compared to
      the CCl4 group (p<0.001). However, it was still significantly higher than control
      (p<0.001) with no significant difference between the groups that received stem
      cells. Histopathological examination of liver tissue showed that stem cells have
      a significant antifibrotic effect. Concerning gene expression, the collagen gene
      (rat) was highly expressed in the CCl4 group whereas its expression was
      significantly decreased after administration of stem cells. Human albumin and
      matrix metalloproteinase (MMP2) genes were expressed in liver tissues in the
      groups that received stem cells. Highest expression was in the group that
      received un-differentiated cells I.V. human UCB CD34(+) stem cells can ameliorate
      liver fibrosis in rats. 

PMID- 24855555
TI  - Effect of Recombinant Human Erythropoietin On the Stemness of Bone Marrow-derived
      Mesenchymal Stem Cells in vitro.
AB  - The purpose of this study was to investigate the effects of the recombinant human
      erythropoietin (rhEPO) on proliferative and multi-differentiation potential of
      the bone marrow-derived mesenchymal stem cells (MSCs). The MSCs were isolated
      primarily from bone marrow of adult rat and purified at increasing passage. A
      purified population of MSCs can be obtained about 2 weeks after the initiation of
      culture. After three passages (P3-MSCs), bone marrow-derived adherent cells were
      identified, then different concentrations of rhEPO (0.1, 1, 5, 10, 100 U/ml) was
      added into the Passage-3 cells which had been identified. The expression of the
      surface markers in adherent cells was detected by the flow cytometry. The mRNA
      levels of transcription factors OCT4, SOX2, Nanog and TERT were measured by
      reverse transcription-polymerase chain reaction (RT-PCR). The results showed that
      CD29 and CD90 were positive in MSCs, but not CD33, CD44 and CD45, and the cells
      could differentiate into multiple lineages such as osteocytes and adipocytes. The
      expression of OCT4, SOX2, TERT, Nanog mRNA were up-regulated by the treatment of
      EPO. The effect of EPO was the most obvious when its concentration was 5U/mL
      after 12h. we conclude that MSCs can not only perserve characteristics of stem
      cells but also maintain its multi-lineage differentiation potential after
      appropriate treatment of EPO. 

PMID- 24855556
TI  - Straightforward access to mono- and bis-cycloplatinated helicenes that display
      circularly polarized phosphorescence using crystallization resolution methods.
AB  - Enantiopure mono-cycloplatinated-[8]helicene and bis-cycloplatinated-[6]helicene
      derivatives were prepared through column chromatography combined with
      crystallization of diastereomeric complexes using a chiral ancillary sulfoxide
      ligand. The UV-visible spectra, circular dichroism, molar rotations, and
      (circularly polarized) luminescence activity of these new helical complexes have
      been examined in detail and analysed with the help of first-principles quantum
      chemical calculations.

PMID- 24855557
TI  - Posterior localization of ApVas1 positions the preformed germ plasm in the sexual
      oviparous pea aphid Acyrthosiphon pisum.
AB  - BACKGROUND: Germline specification in some animals is driven by the maternally
      inherited germ plasm during early embryogenesis (inheritance mode), whereas in
      others it is induced by signals from neighboring cells in mid or late development
      (induction mode). In the Metazoa, the induction mode appears as a more prevalent
      and ancestral condition; the inheritance mode is therefore derived. However,
      regarding germline specification in organisms with asexual and sexual
      reproduction it has not been clear whether both strategies are used, one for each
      reproductive phase, or if just one strategy is used for both phases. Previously
      we have demonstrated that specification of germ cells in the asexual viviparous
      pea aphid depends on a preformed germ plasm. In this study, we extended this work
      to investigate how germ cells were specified in the sexual oviparous embryos,
      aiming to understand whether or not developmental plasticity of germline
      specification exists in the pea aphid. RESULTS: We employed Apvas1, a Drosophila
      vasa ortholog in the pea aphid, as a germline marker to examine whether germ
      plasm is preformed during oviparous development, as has already been seen in the
      viviparous embryos. During oogenesis, Apvas1 mRNA and ApVas1 protein were both
      evenly distributed. After fertilization, uniform expression of Apvas1 remained in
      the egg but posterior localization of ApVas1 occurred from the fifth nuclear
      cycle onward. Posterior co-localization of Apvas1/ApVas1 was first identified in
      the syncytial blastoderm undergoing cellularization, and later we could detect
      specific expression of Apvas1/ApVas1 in the morphologically identifiable germ
      cells of mature embryos. This suggests that Apvas1/ApVas1-positive cells are
      primordial germ cells and posterior localization of ApVas1 prior to
      cellularization positions the preformed germ plasm. CONCLUSIONS: We conclude that
      both asexual and sexual pea aphids rely on the preformed germ plasm to specify
      germ cells and that developmental plasticity of germline specification, unlike
      axis patterning, occurs in neither of the two aphid reproductive phases.
      Consequently, the maternal inheritance mode implicated by a preformed germ plasm
      in the oviparous pea aphid becomes a non-canonical case in the Hemimetabola,
      where so far the zygotic induction mode prevails in most other studied insects.

PMID- 24855558
TI  - Incidence and severity of myofiber branching with regeneration and aging.
AB  - BACKGROUND: Myofibers with an abnormal branching cytoarchitecture are commonly
      found in muscular dystrophy and in regenerated or aged nondystrophic muscles.
      Such branched myofibers from dystrophic mice are more susceptible to damage than
      unbranched myofibers in vitro, suggesting that muscles containing a high
      percentage of these myofibers are more prone to injury. Little is known about the
      regulation of myofiber branching. METHODS: To gain insights into the formation
      and fate of branched myofibers, we performed in-depth analyses of single
      myofibers isolated from dystrophic and nondystrophic (myotoxin-injured or aged)
      mouse muscles. The proportion of branched myofibers, the number of branches per
      myofiber and the morphology of the branches were assessed. RESULTS: Aged
      dystrophic mice exhibited the most severe myofiber branching as defined by the
      incidence of branched myofibers and the number of branches per myofiber, followed
      by myotoxin-injured, wild-type muscles and then aged wild-type muscles. In
      addition, the morphology of the branched myofibers differed among the various
      models. In response to either induced or ongoing muscle degeneration, branching
      was restricted to regenerated myofibers containing central nuclei. In myotoxin
      injured muscles, the amount of branched myofibers remained stable over time.
      CONCLUSION: We suggest that myofiber branching is a consequence of myofiber
      remodeling during muscle regeneration. Our present study lays valuable groundwork
      for identifying the molecular pathways leading to myofiber branching in
      dystrophy, trauma and aging. Decreasing myofiber branching in dystrophic patients
      may improve muscle resistance to mechanical stress.

PMID- 24855559
TI  - MicroRNA-206 suppresses gastric cancer cell growth and metastasis.
AB  - Gastric cancer is one of the leading causes of cancer death world-wide and
      carries a high rate of metastatic risk. In addition to other protein-coding
      oncogenes and tumor suppressor genes, microRNAs play an important role in gastric
      cancer tumorigenic progression. Here, we show that miR-206 is expressed at
      markedly low levels in a cohort of gastric tumors compared to their matching
      normal tissues, and in a number of gastric cancer cell lines. Down-regulation of
      miR-206 was particularly significant in tumors with lymphatic metastasis, local
      invasion, and advanced TNM staging. We find that forced expression of miR-206
      suppressed the proliferation, colony-formation, and xenograft tumorigenesis of
      SCG-7901 cells, a line of gastric cancer cells. Forced expression of miR-206 also
      suppressed SCG-7901 cell migration and invasion, as well as metastasis in cell
      culture or tail-vein injected mouse models, respectively. The anti-metastatic
      effect of miR-206 is likely mediated by targeting metastasis regulatory genes
      STC2, HDAC4, KLF4, IGF1R, FRS2, SFRP1, BCL2, BDNF, and K-ras, which were
      drastically down-regulated by stable expression of exogenous miR-206 in SCG-7901
      cells. Taken together, our results indicate that miR-206 is a tumor suppressor of
      gastric cancer acting at steps that regulate metastasis. 

PMID- 24855560
TI  - The role of mitochondria in longevity and healthspan.
AB  - The role of mitochondria in aging and disease remains contentious more than 40
      years after the mitochondrial free radical theory of aging was first proposed. As
      part of a wider cross-journal series on contemporary mitochondrial biology,
      Longevity & Healthspan presents a thematic series of four reviews that discuss
      the evidence for and against the modern incarnations of the theory, and examine
      the relevance of mitochondrial membrane phospholipid unsaturation and the
      interactions of mitochondria with sex hormones. 

PMID- 24855561
TI  - Species and genus level resolution analysis of gut microbiota in Clostridium
      difficile patients following fecal microbiota transplantation.
AB  - BACKGROUND: Clostridium difficile is an opportunistic human intestinal pathogen,
      and C. difficile infection (CDI) is one of the main causes of antibiotic-induced
      diarrhea and colitis. One successful approach to combat CDI, particularly
      recurrent form of CDI, is through transplantation of fecal microbiota from a
      healthy donor to the infected patient. In this study we investigated the distal
      gut microbial communities of three CDI patients before and after fecal microbiota
      transplantation, and we compared these communities to the composition of the
      donor's fecal microbiota. We utilized phylogenetic Microbiota Array, high
      throughput Illumina sequencing, and fluorescent in situ hybridization to profile
      microbiota composition down to the genus and species level resolution. RESULTS:
      The original patients' microbiota had low diversity, was dominated by members of
      Gammaproteobacteria and Bacilli, and had low numbers of Clostridia and
      Bacteroidia. At the genus level, fecal samples of CDI patients were rich in
      members of the Lactobacillus, Streptococcus, and Enterobacter genera. In
      comparison, the donor community was dominated by Clostridia and had significantly
      higher diversity and evenness. The patients' distal gut communities were
      completely transformed within 3 days following fecal transplantation, and these
      communities remained stable in each patient for at least 4 months. Despite
      compositional differences among recipients' pre-treatment gut microbiota, the
      transplanted gut communities were highly similar among recipients post
      transplantation, were indistinguishable from that of the donor, and were rich in
      members of Blautia, Coprococcus, and Faecalibacterium. In each case, the gut
      microbiota restoration led to a complete patient recovery and symptom
      alleviation. CONCLUSION: We conclude that C. difficile infection can be
      successfully treated by fecal microbiota transplantation and that this leads to
      stable transformation of the distal gut microbial community from the one abundant
      in aerotolerant species to that dominated by members of the Clostridia.

PMID- 24855563
TI  - Durable responses and reversible toxicity of high-dose interleukin-2 treatment of
      melanoma and renal cancer in a Community Hospital Biotherapy Program.
AB  - BACKGROUND: High-dose interleukin-2 (IL-2) has been FDA-approved for over 20
      years, but it is offered only at a small number of centers with expertise in its
      administration. We analyzed the outcomes of patients receiving high-dose IL-2 in
      relation to the severity of toxicity to ascertain if response or survival were
      adversely affected. METHODS: A retrospective analysis of the outcomes of 500
      patients with metastatic renal cell carcinoma (RCC) (n = 186) or melanoma (n =
      314) treated with high-dose IL-2 between 1997 and 2012 at Providence Cancer
      Center was performed. IL-2 was administered at a dose of 600,000 international
      units per kg by IV bolus every 8 hours for up to 14 doses. A second cycle was
      administered 16 days after the first and patients with tumor regression could
      receive additional cycles. Survival and anti-tumor response were analyzed by
      diagnosis, severity of toxicity, number of IL-2 cycles and subsequent therapy.
      RESULTS: The objective response rate in melanoma was 28% (complete 12% and
      partial 16%), and in RCC was 24% (complete 7% and partial 17%). The 1-, 2- and 3
      year survivals were 59%, 41% and 31%, for melanoma and 75%, 56% and 44%, for RCC,
      respectively. The proportion of patients with complete or partial response in
      both melanoma and RCC was higher in patients who a) required higher phenylephrine
      doses to treat hypotension (p < 0.003), b) developed acidosis (bicarbonate < 19
      mmol (p < 0.01)), or c) thrombocytopenia (<50, 50-100, >100,000 platelets; p <
      0.025). The proportion achieving a complete or partial response was greater in
      patients with melanoma who received 5 or more compared with 4 or fewer IL-2
      cycles (p < 0.0001). The incidence of death from IL-2 was less than 1% and was
      not higher in patients who required phenylephrine. CONCLUSIONS: High-dose IL-2
      can be administered safely; severe toxicity including hypotension is reversible
      and can be managed in a community hospital. The tumor response and survival
      reported here are superior to the published literature and support treating
      patients to their individualized maximum tolerated dose. IL-2 should remain part
      of the treatment paradigm in selected patients with melanoma and RCC.

PMID- 24855562
TI  - Targeting tumor-necrosis factor receptor pathways for tumor immunotherapy.
AB  - With the success of ipilimumab and promise of programmed death-1 pathway-targeted
      agents, the field of tumor immunotherapy is expanding rapidly. Newer targets for
      clinical development include select members of the tumor necrosis factor receptor
      (TNFR) family. Agonist antibodies to these co-stimulatory molecules target both T
      and B cells, modulating T-cell activation and enhancing immune responses. In
      vitro and in vivo preclinical data have provided the basis for continued
      development of 4-1BB, OX40, glucocorticoid-induced TNFR-related gene, herpes
      virus entry mediator, and CD27 as potential therapies for patients with cancer.
      In this review, we summarize the immune response to tumors, consider preclinical
      and early clinical data on select TNFR family members, discuss potential
      translational challenges and suggest possible combination therapies with the aim
      of inducing durable antitumor responses. 

PMID- 24855566
TI  - Dermatopathology: An abridged compendium of words. A discussion of them and
      opinions about them. Part 4.

PMID- 24855565
TI  - Crystallization of Amino Acids on a 21-well Circular PMMA Platform using Metal
      Assisted and Microwave-Accelerated Evaporative Crystallization.
AB  - We describe the design and the use of a circular poly(methyl methacrylate) (PMMA)
      crystallization platform capable of processing 21 samples in Metal-Assisted and
      Microwave-Accelerated Evaporative Crystallization (MA-MAEC). The PMMA platforms
      were modified with silver nanoparticle films (SNFs) to generate a microwave
      induced temperature gradient between the solvent and the SNFs due to the marked
      differences in their physical properties. Since amino acids only chemisorb on to
      silver on the PMMA platform, SNFs served as selective and heterogeneous
      nucleation sites for amino acids. Theoretical simulations for electric field and
      temperature distributions inside a microwave cavity equipped with a PMMA platform
      were carried out to determine the optimum experimental conditions, i.e.,
      temperature variations and placement of the PMMA platform inside a microwave
      cavity. In addition, the actual temperature profiles of the amino acid solutions
      were monitored for the duration of the crystallization experiments carried out at
      room temperature and during microwave heating. The crystallization of five amino
      acids (L-threonine, L-histidine, L-leucine, L-serine and L-valine HCl) at room
      temperature (control experiment) and using MA-MAEC were followed by optical
      microscopy. The induction time and crystal growth rates for all amino acids were
      determined. Using MA-MAEC, for all amino acids the induction times were
      significantly reduced (up to ~8-fold) and the crystal growth rates were increased
      (up to ~50-fold) as compared to room temperature crystallization, respectively.
      All crystals were characterized by Raman spectroscopy and powder x-ray
      diffraction, which demonstrated that the crystal structures of all amino acids
      grown at room temperature and using MA-MAEC were similar.

PMID- 24855564
TI  - Fibrinogen alpha-chain-derived peptide is upregulated in hippocampus of rats
      exposed to acute morphine injection and spontaneous alternation testing.
AB  - Fibrinogen is a secreted glycoprotein that is synthesized in the liver, although
      recent in situ hybridization data support its expression in the brain. It is
      involved in blood clotting and is released in the brain upon injury. Here, we
      report changes in the extracellular levels of fibrinogen alpha-chain-derived
      peptides in the brain after injections of saline and morphine. More specifically,
      in order to assess hippocampus-related working memory, an approach pairing in
      vivo microdialysis with mass spectrometry was used to characterize extracellular
      peptide release from the hippocampus of rats in response to saline or morphine
      injection coupled with a spontaneous alternation task. Two fibrinopeptide A
      related peptides derived from the fibrinogen alpha-chain-fibrinopeptide A
      (ADTGTTSEFIEAGGDIR) and a fibrinopeptide A-derived peptide (DTGTTSEFIEAGGDIR)
      were shown to be consistently elevated in the hippocampal microdialysate.
      Fibrinopeptide A was significantly upregulated in rats exposed to morphine and
      spontaneous alternation testing compared with rats exposed to saline and
      spontaneous alternation testing (P < 0.001), morphine alone (P < 0.01), or saline
      alone (P < 0.01), respectively. The increase in fibrinopeptide A in rats
      subjected to morphine and a memory task suggests that a complex interaction
      between fibrinogen and morphine takes place in the hippocampus.

PMID- 24855567
TI  - Dermoscopic characteristics of nodular squamous cell carcinoma and
      keratoacanthoma.
AB  - BACKGROUND: Nodular squamous cell carcinoma (SCC) and keratoacanthoma (KA) may
      mimic a variety of other benign and malignant non-pigmented nodules. OBJECTIVES:
      To analyze the dermoscopic characteristics of nodular SCC and KA.
      PATIENTS/METHODS: Retrospective analysis of 50 nodular SCCs and 8 KAs collected
      from a tertiary dermatology referral center and a private dermatology practice in
      Melbourne, Australia, between 1 September 2009 and 1 October 2012. All lesions
      were nodules; defined as firm, elevated, round, palpable tumors with a diameter
      of 5 mm or more. Clinical and dermoscopic images were evaluated by two examiners
      in consensus. RESULTS: Signs of keratinization were frequently observed and
      included keratin crust/scale (90% of SCCs, 100% of KAs), central keratin mass
      (32% of SCCs, 88% of KAs), white structureless areas (66% of SCCs, 50% of KAs),
      white circles (32% of SCCs, 38% of KAs) and white keratin pearls (14% of SCCs,
      12% of KAs). Hemorrhage was present in 72% of SCCs and 88% of KAs and
      preferentially occurred centrally and in areas of keratinization. For nodular
      SCCs and KAs, we observed glomerular vessels (42% and 25% respectively), linear
      irregular vessels (36% and 25% respectively), atypical vessels (30% and 38%
      respectively) and hairpin vessels (30% and 25% respectively). CONCLUSIONS:
      Hemorrhage, keratinization and vascular features (glomerular, hairpin and linear
      irregular morphologies) are useful in diagnosing both nodular SCC and KA. Further
      research on the comparative dermoscopic characteristics of a range of amelanotic
      nodules is important in order to improve diagnosis of these clinically
      challenging tumors.

PMID- 24855568
TI  - Papulonecrotic tuberculid-clinicopathologic and molecular features of 12 Indian
      patients.
AB  - BACKGROUND: Papulonecrotic tuberculid (PNT) is said to be a hypersensitivity
      reaction to M. tuberculosis. Some reports indicate that organisms are
      demonstrable by polymerase chain reaction (PCR). METHODS: We describe 12 patients
      with PNT over 6 years. We reviewed the histopathologic features, clinical data
      and follow-up. PCR for M. tuberculosis DNA was done in all cases. RESULTS: There
      were 7 men and 5 women. The ages ranged from 3-58 years. Upper limbs were
      commonly involved (8 cases). All patients had multiple papulonodular lesions, 5
      showed ulceration and scarring. Mantoux test was strongly positive in all. Seven
      patients had systemic tuberculosis. On microscopy, necrosis was seen in 11 cases,
      varying from minimal to extensive. Epithelioid granulomas were common, except for
      1 case with palisading and interstitial patterns. The infiltrate showed mostly
      lymphocytes, while 3 cases showed eosinophils. Vasculitis was seen in 8 cases.
      Two cases had dermal mucin, one also with interface dermatitis. This patient had
      concurrent LE. Mycobacterial DNA was detectable by PCR in 3 cases. Seven patients
      showed improvement/resolution of lesions on treatment. CONCLUSIONS: PNT is a rare
      disease. A positive PCR reiterates the question whether these are "tuberculids".
      PNT may be better classified as true cutaneous tuberculosis and patients screened
      for systemic disease.

PMID- 24855570
TI  - Melanocytic nevi and melanoma: overlapping criteria-the degree is the key.

PMID- 24855569
TI  - Papillary adenocarcinoma in situ of the skin: report of four cases.
AB  - Although rare isolated cases of adenocarcinoma in situ of skin have been reported
      in the literature, adenocarcinoma in situ of skin as a concept and as a
      diagnostic category has not been established in the field of dermatopathology. In
      this work, four cases of papillary adenocarcinoma in situ of the skin are
      presented. In addition, the notion that lesions previously reported in the
      medical literature under the term of "papillary eccrine adenoma" are actually
      adenocarcinoma in situ is discussed. 

PMID- 24855571
TI  - Tufted hemangioma: clinical case and literature review.
AB  - Tufted hemangiomas are relatively rare benign vascular proliferations that are
      congenital or appear during the first years of life. Herein we present an
      additional case of tufted hemangioma that appeared one year after birth and
      discuss its histopathological criteria and differential diagnosis with malignant
      vascular proliferations including sarcoma Kaposi, angiosarcoma and kaposiform
      hemangioendothelioma. 

PMID- 24855572
TI  - Longterm digital monitoring in the diagnosis and management of congenital nevi of
      the nail apparatus showing pseudo-Hutchinson's sign.

PMID- 24855573
TI  - Spitz nevus on the sole of the foot presenting with transepidermal elimination.
AB  - A 10-year-old Japanese girl presented with a rhomboid-shaped brown macule, 4x3 mm
      in size, on the sole of the right foot. Dermoscopic examination revealed a number
      of black dots and globules on the ridges of the skin, marking an area of
      symmetrical brown pigmentation. On the periphery, a streak-like arrangement of
      black dots/globules on the brown pigmentation was observed along the ridges,
      simulating a "starburst" pattern. The lesion was excised and histological
      examination showed a symmetrical wedge-shaped compound melanocytic lesion that
      consisted of junctional and intradermal nests of a mixture of large spindle and
      epithelioid cells. None of the cells were atypical, and maturation of the cells
      with increasing depth was observed. From these findings, a diagnosis of Spitz
      nevus was made. Transepidermal elimination of nevus cell nests was observed and
      there were small groups of degenerated melanin-laden cells in the cornified
      layer. Masson Fontana stain revealed fine melanin deposits in the nevus cells of
      the junctional and intradermal nests, as well as heavy melanin deposits in the
      small groups of degenerated cells in the cornified layer. The distribution of
      melanin may contribute to a unique dermoscopic finding in this case. 

PMID- 24855574
TI  - Non-choroidal yellow melanoma showing positive staining with Sudan Black
      consistent with the presence of lipofuscin: a case report.
AB  - A case of a predominantly yellow primary superficial spreading melanoma arising
      on the back of a 44-year-old woman is presented. Possible causes of the clinical
      and dermatoscopic yellow color are discussed. Staining with the histochemical
      stain, Sudan Black, revealed a differential uptake compared to a closely matched
      control melanoma. We speculate that the clinical and dermatoscopic yellow color
      could be due to the presence of increased amounts of the pigment lipofuscin,
      which is known to produce subtle orange color in some choroidal melanomas. 

PMID- 24855575
TI  - Yellow color upon dermatoscopy does not exclude melanoma!

PMID- 24855576
TI  - Solitary trichoepithelioma in an 8-year-old child: clinical, dermoscopic and
      histopathologic findings.
AB  - Solitary trichoepithelioma (TE) is a rare, benign tumor of follicular origin that
      in certain cases is difficult to differentiate from basal cell carcinoma (BCC).
      We report the case of an 8-year-old girl with a pale pink, soft lesion on the
      neck. The clinical image of the lesion was equivocal, while some dermoscopic
      findings-blue-gray globules and arborizing vessels-could not exclude the presence
      of BCC from the differential diagnosis, although that would have been a very
      unlikely case considering the age of the patient. The histopathologic examination
      established the diagnosis of TE. Given the occasion of this challenging case we
      try to list the key clinical, dermoscopic and histopathological characteristics
      of TE and BCC in order to elucidate the differential diagnosis of these two
      entities. 

PMID- 24855577
TI  - A case of primitive non-neural granular cell tumor presenting as a single
      painless bleeding nodule.
AB  - Primitive non-neural granular cell tumor is a rare tumor of uncertain lineage
      that clinically presents as a solitary painless nodule most typically on the
      extremity or trunk of an adult. We report the case of a 20-year-old man with a
      small reddish papule on the abdomen, measuring about 2 x 3 mm, surrounded by a
      faint erythematous halo. Dermoscopy examination shows diffuse red color and weak
      whitish striae. However, only histological and immunohistochemical evaluation
      allowed us to perform the correct diagnosis. 

PMID- 24855578
TI  - An atypical pigmented lesion.

PMID- 24855579
TI  - An atypical pigmented lesion on the nose-Answer.

PMID- 24855580
TI  - Nodular melanoma: five consecutive cases in a general practice with polarized and
      non-polarized dermatoscopy and dermatopathology.
AB  - BACKGROUND: The incidence of nodular melanoma (NM) has been consistently
      described as at least 10-15% of total melanomas for over 15 years despite
      advances in diagnostic algorithms and medical technology. NMs are strongly
      correlated with faster rates of growth and poorer prognosis and thus provide
      clinicians with a challenge for early recognition. OBJECTIVE: To evaluate
      diagnostic clues of consecutive histopathologically proven NMs in one general
      practice with particular emphasis on dermatoscopic characteristics and compare
      this to the published literature. METHOD: A retrospective observational study was
      performed of five consecutive histologically proven NM, from a total of 212
      consecutive melanomas from a general practice in Brisbane, Queensland, Australia.
      Dermatoscopic images, both polarized and non-polarized, which appears to be a
      unique resource, and dermatopathologic slides were available for all lesions.
      RESULTS: All of the NMs in this series were pigmented although one was
      hypomelanotic. Two of them were symmetrical. The most highly sensitive clues to
      NM were gray or blue structures and polarizing-specific white lines. LIMITATIONS:
      Due to the small number of NMs in this report no statistical significance can be
      attributed to the observational findings. CONCLUSION: THIS SMALL SERIES SUPPORTS
      WHAT IS ALREADY KNOWN: that a significant proportion of NMs may be
      dermatoscopically symmetrical but that known clues to melanoma are frequently
      present. Nodular lesions, pigmented or non-pigmented, should be excised to
      exclude NM if there is any clue to malignancy, regardless of symmetry, unless a
      confident specific benign diagnosis can be made.

PMID- 24855581
TI  - Atypical fibroxanthoma of the cheek-case report with dermatoscopy and
      dermatopathology.
AB  - We present a case report of an atypical fibroxanthoma on the cheek of a 73-year
      old man. Clinical, dermatoscopic and dermatopathologic images are presented. 

PMID- 24855582
TI  - The reason for red streaks on dermoscopy in the distal part of a subungual
      hemorrhage.

PMID- 24855583
TI  - Isokinetic Strength and Performance in Collegiate Women's Soccer.
AB  - Soccer research in exercise science has focused on men's soccer, while women's
      soccer has been underrepresented in training studies, as well as in studies
      focusing on physiological variables. The purpose of this study was to examine
      anthropometric data and selected physiological and biomechanical variables of
      importance as they correlates to performance variables such as ball velocity and
      distance, specifically in female collegiate soccer players. Twenty-two NCAA
      Division I female soccer athletes participated in the study. Body composition,
      muscular strength, explosive power, aerobic power, acceleration, speed, and
      agility were tested in each athlete. Knee torque (KT) and hip torque (HT) were
      also measured on both legs. Kicking accuracy and velocity were examined. A
      correlation was found between KT and KV (r=0.93), as well as vertical jump and KV
      (r=0.91). Aerobic power (r=0.93), agility (r=0.88), and vertical jump (r=0.84)
      were highly correlated to BF%. These data suggest that significant relationships
      do exist between peak knee and hip torque, agility, lean body mass, strength, and
      explosive power with soccer-specific variables such as kick velocity (KV).
      Contributing to the body of data on female soccer athletes and variables
      important in performance is essential as the population engaged in the sport
      continues to increase.

PMID- 24855585
TI  - Vasodilators in Acute Heart Failure: Review of the Latest Studies.
AB  - Vasodilators play an important role in the management of acute heart failure,
      particularly when increased afterload is the precipitating cause of
      decompensation. The time-honored approach to afterload reduction has been largely
      focused on use of intravenous nitrovasodilators and, when properly dosed, this
      class of agents does provide substantial symptom relief for patients with acute
      hypertensive heart failure. Despite this, nitrovasodilators have never been shown
      to diminish mortality or provide any post-discharge outcome benefit leading to an
      on-going search for viable and more effective alternatives. While no new
      vasodilators have been approved for use in acute heart failure since nesiritide
      more than a decade ago, a number of novel agents have been developed, with some
      showing significant promise in recent clinical trials. In this review, we
      summarize the latest study data as it relates to vasodilator therapy and provide
      a glimpse into the not too distant future state of acute heart failure care.

PMID- 24855584
TI  - Ras-Mediated Signal Transduction and Virulence in Human Pathogenic Fungi.
AB  - Signal transduction pathways regulating growth and stress responses are areas of
      significant study in the effort to delineate pathogenic mechanisms of fungi. In
      depth knowledge of signal transduction events deepens our understanding of how a
      fungal pathogen is able to sense changes in the environment and respond
      accordingly by modulation of gene expression and re-organization of cellular
      activities to optimize fitness. Members of the Ras protein family are important
      regulators of growth and differentiation in eukaryotic organisms, and have been
      the focus of numerous studies exploring fungal pathogenesis. Here, the current
      data regarding Ras signal transduction are reviewed for three major pathogenic
      fungi: Cryptococcus neoformans, Candida albicans and Aspergillus fumigatus.
      Particular emphasis is placed on Ras-protein interactions during control of
      morphogenesis, stress response and virulence.

PMID- 24855587
TI  - HIV testing among United States high school students at the state and national
      level, Youth Risk Behavior Survey 2005-2011.
AB  - BACKGROUND: Human immunodeficiency virus (HIV) remains an important public health
      issue and CDC recommends routine HIV screening for Americans aged 13-64.
      Adolescents and young adults are disproportionately affected compared to the
      overall population. We analyzed self-reported HIV testing and related risk
      behaviors at the state and national level among youths who had sexual
      intercourse, with a focus on state level differences. METHODS: This study used
      the state and national Youth Risk Behaviors Surveys 2005-2011. It included a
      total of 59,793 national-level observations and 39,421 state-level observations
      of US high school students, of which respectively 28,177 and 13,916 reported ever
      having sexual intercourse. The outcome of interest was having ever been tested
      for HIV. The risk behaviors were condom use at last intercourse, number of sexual
      partners in lifetime, age at first intercourse, ever forced sexual intercourse,
      and ever illegal injection drug use. Analyses performed included logistic
      regression and t-test analyses. RESULTS: HIV testing was positively associated
      with HIV-related risk behaviors among sexually active high school students.
      However, HIV testing remained relatively low (22%) between 2005 and 2011, even
      for those engaging in risk behaviors. Results differed among the only 7 states
      that monitored HIV testing through YRBS, most commonly with respect to HIV
      testing and condom use. CONCLUSIONS: Routine HIV testing is critical for early
      identification of HIV, which was set as a priority in a recent Executive Order.
      Our data suggest further efforts are needed to achieve widespread uptake of HIV
      testing among high school students. Furthermore, differences observed across
      states likely reflect different needs and should be followed up closely by
      states. Finally, having accurate data that reflects the reality of youths' lives
      is crucial for efficient prevention planning. Thus, more states should consider
      collecting HIV testing data to evaluate uptake of HIV testing among youth.

PMID- 24855588
TI  - Hot topics and application trends of the anammox biotechnology: a review by
      bibliometric analysis.
AB  - Anammox has been extensively identified as a novel and sustained biotechnology
      for wastewater treatment. This study was conducted to evaluate the hot topics and
      application trends of anammox biotechnology by bibliometric analysis. The results
      show that "Water science and technology" and "Environmental science ecology" are
      the prevalent journal and category in this field. Many researches about "process"
      and "inhibition" have been carried out to conquer common challenges of anammox
      biotechnology in its actual engineering application. "Fluorescence in situ
      hybridization" continues to be the leading rRNA microbiological analysis method
      after its first application. Most importantly, "Completely autotrophic nitrogen
      removal over nitrite (CANON)", "Sequencing batch reactors (SBR) for anammox
      operation", "black water treatment" and "anammox biofilm" are identified as the
      prevalent process type, reactor type, wastewater type and bacterial aggregation
      form in anammox research currently, which forecasts the further engineering
      application direction of anammox biotechnology. The study will be useful for the
      researchers to acquaint the current state and the application trends in anammox
      biotechnology field. 

PMID- 24855589
TI  - Are virtues national, supranational, or universal?
AB  - Many studies investigated cultural differences in values, most notably by
      Hofstede and Schwarz. Relatively few have focused on virtues, a related and
      important concept in contemporary social science. The present paper examines the
      similarities and differences between nations, or blocks of - culturally related -
      nations on the perceived importance of virtues. Adults (N = 2.809 students) from
      14 countries were asked to freely mention which virtues they found important to
      practice in daily life, and next to rate a list of 15 virtues, which reflect the
      most frequently mentioned categories in The Netherlands, as found in a previous
      study. The 14 nations included the United States, Mexico, nine European and three
      Asian nations. For the free-listed virtues, we compared the top-ten lists of most
      frequently mentioned virtues across the nations. We used a correspondence
      analysis on the frequency table to assess the relationships between the virtues
      and nations. For the 15 virtues ratings, a MANOVA, and follow-up ANOVA's were
      used to examine effects of nation, age, gender and religion. We found strong
      evidence for relationships between nations and blocks of culturally related
      nations and the importance attached to various virtues. There appear to be some
      country specific virtues, such as generosity in France, but also some relatively
      universal virtues, most notably honesty, respect, and kindness. 

PMID- 24855590
TI  - Ground water sensitivity to climate variability in the white Bandama basin, Ivory
      Coast.

PMID- 24855586
TI  - Durable bonds at the adhesive/dentin interface: an impossible mission or simply a
      moving target?
AB  - Composite restorations have higher failure rates, more recurrent caries and
      increased frequency of replacement as compared to dental amalgam. Penetration of
      bacterial enzymes, oral fluids, and bacteria into the crevices between the tooth
      and composite undermines the restoration and leads to recurrent decay and
      failure. The gingival margin of composite restora tions is particularly
      vulnerable to decay and at this margin, the adhesive and its seal to dentin
      provides the primary barrier between the prepared tooth and the environment. The
      intent of this article is to examine physico-chemical factors that affect the
      integrity and durability of the adhesive/dentin interfacial bond; and to explore
      how these factors act synergistically with mechanical forces to undermine the
      composite restoration. The article will examine the various avenues that have
      been pursued to address these problems and it will explore how alterations in
      material chemistry could address the detrimental impact of physico-chemical
      stresses on the bond formed at the adhesive/dentin interface.

PMID- 24855591
TI  - Effectiveness of preoperative beta-blockade on intra-operative heart rate in
      vascular surgery cases conducted under regional or local anesthesia.
AB  - BACKGROUND: Preoperative beta-blockade has been posited to result in better
      outcomes for vascular surgery patients by attenuating acute hemodynamic changes
      associated with stress. However, the incremental effectiveness, if any, of beta
      blocker usage in blunting heart rate responsiveness for vascular surgery patients
      who avoid general anesthesia remains unknown. METHODS: We reviewed an existing
      database and identified 213 consecutive vascular surgery cases from 2005-2011
      conducted without general anesthesia (i.e., under monitored anesthesia care or
      regional anesthesia) at a tertiary care Veterans Administration medical center
      and categorized patients based on presence or absence of preoperative beta
      blocker prescription. For this series of patients, with the primary outcome of
      maximum heart rate during the interval between operating room entry to surgical
      incision, we examined the association of maximal heart rate and preoperative beta
      blocker usage by performing crude and multivariate linear regression, adjusting
      for relevant patient factors. RESULTS: Of 213 eligible cases, 137 were prescribed
      preoperative beta-blockers, and 76 were not. The two groups were comparable
      across baseline patient factors and intraoperative medication doses. The beta
      blocker group experienced lower maximal heart rates during the period of
      evaluation compared to the non-beta-blocker group (85 +/- 22 bpm vs. 98 +/- 36
      bpm, respectively; p = 0.002). Adjusted linear regression confirmed a
      statistically-significant association between lower maximal heart rate and the
      use of beta-blockers (Beta = -11.5; 95% CI [-3.7, -19.3] p = 0.004). CONCLUSIONS:
      The addition of preoperative beta-blockers, even when general anesthesia is
      avoided, may be beneficial in further attenuating stress-induced hemodynamic
      changes for vascular surgery patients.

PMID- 24855592
TI  - Knowing the enemy: ant behavior and control in a pediatric hospital of Buenos
      Aires.
AB  - Ant control is difficult in systems even where a variety of control strategies
      and compounds are allowed; in sensitive places such as hospitals, where there are
      often restrictions on the methods and toxicants to be applied, the challenge is
      even greater. Here we report the methods and results of how we faced this
      challenge of controlling ants in a pediatric hospital using baits. Our strategy
      was based on identifying the species present and analyzing their behavior. On the
      one hand, we evaluated outdoors in the green areas of the hospital, the relative
      abundance of ant genera, their food preferences and the behavioral dominances. On
      the other hand, control treatments were performed using separately two boron
      compounds added to sucrose solution which was not highly concentrated to avoid
      constrains due to the viscosity. Most of the species in the food preference test
      accepted sugary food; only one species was recorded to visit it less than the
      protein foods. This result was consistent with the efficacy of control treatments
      by sugary baits within the rooms. For species that showed good acceptance of
      sugar solutions in the preference test outdoors, sugar bait control indoors was
      100& effective. Conversely, for the only species that foraged significantly less
      on sugar food, the bait treatment was ineffective. This work reveals the
      importance of considering the behavior and feeding preferences of the species to
      be controlled by toxic baits. 

PMID- 24855593
TI  - Once-weekly teriparatide increases bone mineral density in the distal 1/10
      radius, but not in the distal 1/3 radius.
AB  - Teriparatide significantly increases bone mineral density (BMD) of the lumbar
      vertebrae and femur and has a strong effect in reducing the risk of bone
      fractures. However, few detailed investigations with dual-energy X-ray
      absorptiometry (DXA) of the effects of teriparatide on the radius have been
      reported; specifically, there are no reports of the use of once-weekly
      teriparatide. In this study, the effect of once-weekly teriparatide in increasing
      BMD was examined in the distal 1/10 of the radius and the distal 1/3 of the
      radius using a DXA system for the radius. In addition, the effect of radius
      positioning, especially accurate correction of rotation and inclination before
      and after administration of teriparatide, was evaluated in an assessment of its
      efficacy. It was found that when positioning was corrected, a significant
      increase in BMD in the distal 1/10 of the radius was observed after 6 months of
      once-weekly teriparatide. In the distal 1/3 of the radius, no significant
      increase of BMD was observed. This suggests that when DXA scans of the radius are
      analyzed with appropriate positioning, weekly teriparatide significantly
      increases BMD in the distal 1/10 of the radius, which is rich in cancellous bone.

PMID- 24855594
TI  - Answering to the domesticability of exotic options and strategies in managing
      Africa's urban landscapes for sustainability beyond 2015.
AB  - This study aims at critically assessing the land management strategies that can
      be instrumental in bringing sound governance to urban landscapes in Africa with
      the view of mapping the potential, minimum conditions for success and constraints
      to doing so. This study is qualitative by approach and case study based by
      design, assesses practices in land management from a few cities (Nairobi, Abuja,
      Harare, Kigali, Johannesburg and Addis Ababa). Peculiarities and differences in
      the practices of land management in these cities is the basis for their
      purposeful selection. The evaluation of the land management practices in these
      cities is in terms of the current realities and the possibility for the
      acceptability of new, exotic but deemed sustainable urban land management styles.
      Noted strongly in this current discourse is that Africa is a region with varied
      of contexts requiring a critical assessment of issues before policy strategies
      are implemented in terms of land tenure, land administration corruption,
      political will and receptivity of the so-called foreign philosophies in urban
      land governance. The study recommends relevant training of the land and planning
      experts in Africa. In addition, there is general need to balance between 'place
      prosperity' with 'people prosperity' as they relate to land management noting
      that space and capital make the difference in sustainable human habitats'
      creation and management. 

PMID- 24855596
TI  - Development and preliminary psychometric evaluation of a self-rated version of
      the Family Accommodation Scale for Obsessive-Compulsive Disorder.
AB  - Family accommodation (FA) in obsessive-compulsive disorder (OCD) refers to family
      members' or significant others' participation in or facilitation of patients'
      rituals and/or avoidance. With recent studies pointing to FA as a predictor of
      poorer treatment outcome, there is heightened interest in developing family-based
      interventions for OCD aimed at reducing FA. The interviewer-rated Family
      Accommodation Scale for OCD (FAS-IR) is the gold standard for assessing the types
      and severity of FA in OCD families. However, the cost of training interviewers
      and the time required for administration may limit its use in some settings. A
      valid self-rated version could be administered for research and clinical purposes
      with minimal burden and has the potential to be more widely used. The present
      study reports on the development and initial psychometric testing of the Family
      Accommodation Scale for OCD-Self Rated Version (FAS-SR). The FAS-SR was compared
      to the FAS-IR in a sample of 41 relatives of individuals with primary OCD,
      demonstrating excellent internal consistency, strong agreement with the FAS-IR,
      and expected convergence with criterion measures. Though further study using the
      self-rated version is needed, these findings suggest that the FAS-SR is a valid
      measure of FA and a time-saving, less costly alternative to the FAS-IR.

PMID- 24855595
TI  - Treatment of Adolescent Substance Use Disorders.
AB  - Significant progress has been made in development and dissemination of evidence
      based behavioral interventions for adolescents with substance use disorders
      (SUD). Medications have also shown promise in reducing substance use when used in
      conjunction with psychosocial treatment for adolescents with SUD, even in the
      context of co-occurring psychopathology. Although the efficacy or "probable
      efficacy" of the behavioral interventions discussed in this review have been
      established based on at least two randomized controlled trials, they produce
      relatively low abstinence rates and modest reductions in substance use that
      attenuate over time. Research has shown that abstinence rates may increase with
      the addition of abstinence-based incentives, however, post-treatment relapse
      rates remain high with few treated adolescents sustaining abstinence one year
      post-treatment. This may be due to the paucity of continuing care or post
      treatment recovery support services and the lack of integrated or concurrent
      treatment for co-occurring psychiatric conditions that contribute to poorer
      treatment outcomes. Thus, despite significant progress, there is clearly room for
      improvement of existing treatment for adolescents with SUD. There is also
      critical need to increase the availability and access to substance and behavioral
      health treatment services for adolescents. Although 10-15% of U.S. high school
      students would currently meet diagnostic criteria for at least one SUD, only 10%
      of those who could benefit from substance treatment receive it. Five-year trends
      showing significant increases in the use of marijuana and nonmedical prescription
      drugs among U. S. high school students are evidence of the shortcomings of
      existing school-based interventions and poor access to community-based substance
      treatment for non-juvenile-justice involved youth. There is clearly a need to
      adapt or develop more effective prevention, early interventions, and treatment
      for youth who are "at risk" as well as the increasing number of adolescents who
      have progressed to more serious substance involvement.

PMID- 24855597
TI  - Voriconazole associated torsades de pointes in two adult patients with
      haematological malignancies.
AB  - Voriconazole can prolong the QT interval contributing to life-threatening cardiac
      arrhythmia. Torsades de pointes is an uncommon but serious complication of
      voriconazole use which may be under-recognised. We present torsades de pointes in
      two patients with underlying haematological malignancy being treated for invasive
      fungal infection with voriconazole. Patients receiving voriconazole should be
      screened and monitored for evidence of QT prolongation, and if prolongation
      detected, consideration given to alternative treatments or more intensive cardiac
      monitoring. 

PMID- 24855598
TI  - Scedosporium prolificans osteomyelitis following penetrating injury: A case
      report.
AB  - Scedosporium prolificans are opportunistic moulds that can cause mycetoma
      following penetrating injuries. This fungus is more virulent than other species
      and treatment options are limited. Here we describe the first known case in the
      UK of S. prolificans osteomyelitis, in a 4 year old following penetrating injury.
      Successful outcome with limb salvage and foot function is achieved after repeated
      surgical debridement, and combination chemotherapy with voriconazole/terbinafine.

PMID- 24855599
TI  - Twofer anti-vascular therapy targeting sphingosine-1-phosphate for breast cancer.

PMID- 24855600
TI  - The apical junctional complex in respiratory diseases.
AB  - The epithelium, including the respiratory system, acts as a selective gate
      between the outside environment and underlying tissue. Epithelial cells are
      polarized due to the formation of the apical junctional complex, which includes
      adherent junctions and tight junctions. Endothelial cells are one of the most
      important cellular constituents of blood vessels. Endothelial junctional proteins
      play important roles in tissue integrity as well as in vascular permeability,
      leukocyte extravasation, and angiogenesis. This review focuses on the apical
      junctional complex in respiratory diseases. 

PMID- 24855601
TI  - Gastroprotective Effects of Glutinous Rice Extract against Ethanol-, Indomethacin
      , and Stress-induced Ulcers in Rats.
AB  - This study was designed to evaluate the efficacy of an orally administered
      aqueous extract of glutinous rice (GRE) to protect against acute gastric mucosal
      lesions induced by ethanol, indomethacin, and water immersion restraint stress in
      rats and to characterize the active substances responsible for the protection.
      GRE was shown to dose-dependently prevent the gastric lesions induced by the
      above ulcerogenic treatments at doses of 30 to 300 mg/kg. GRE treatment increased
      the gastric mucin content and partially blocked the ethanol-induced depletion of
      the gastric mucus layer. Also, it increased the nonprotein sulfhydryl
      concentration in the gastric mucosa. The gastroprotective action of GRE was
      markedly enhanced by co-treatment with 4-8 mg/kg tea extracts. The activity of
      GRE was completely lost by heat treatment at 80C for 3 min or treatment with
      0.01% pepsin at 37C for 1 h. Protein extraction studies indicated that prolamins
      are involved in the gastroprotective activity of GRE. Our results suggest that
      glutinous rice proteins are useful for the prevention and treatment of gastritis
      and peptic ulcer. 

PMID- 24855603
TI  - Medullary sponge kidney on retrograde pyelography.
AB  - A woman aged 31 had recurrent urinary tract infection with bloody urine. A series
      image of medullary sponge kidney presented by intravenous urography (IVU) was
      detected dynamically by retrograde pyelography (RP). Other than ultrasonography
      and IVU, RP is also a reliable method to detect medullary sponge kidney. 

PMID- 24855602
TI  - Comparison of the Outcome in Bilateral Staged Total Hip Arthroplasty: Modified
      Two-Incision Minimally Invasive Technique versus the Conventional Posterolateral
      Approach.
AB  - This retrospective study was undertaken to compare the outcomes of staged
      bilateral total hip arthroplasty (THA) by the conventional approach with those of
      two-incision minimally invasive (MIS-2) THA in terms of clinical and radiological
      results, complications, and patient preferences. Twenty-two patients aged 30 to
      80 years underwent staged bilateral THA. The conventional posterolateral approach
      was used on the first hips treated and a modified MIS-2 approach on the second
      hips. The mean time between the first and second procedures was 73.8 months, and
      the patients were followed up for at least 12 months after both procedures. At
      the last follow-up visits, THA via the MIS-2 approach was found to provide
      significantly earlier partial-weight-bearing ambulation, better postoperative
      Harris hip scores, and better ability to sit cross-legged and was found to be
      more preferred by patients than conventional THA. There were no significant
      differences in the complication rates for the two approaches. The present results
      show that MIS-2 THA is as safe as the conventional posterolateral approach in
      experienced hands and presents no additional complication risks. 

PMID- 24855604
TI  - Terrible stent thrombosis induced by a treadmill test performed three days after
      percutaneous coronary intervention.
AB  - Generally, early exercise after coronary stenting is considered safe, but
      isolated cases of acute stent thrombosis have been associated with the
      performance of a treadmill exercise test after percutaneous coronary intervention
      (PCI). The treadmill exercise test is often used to noninvasively assess the
      functional result of PCI. In this report, we describe a case of terrible stent
      thrombosis related to an exercise test performed 3 days after stenting, and the
      patient died as the result of an intractable thrombus. 

PMID- 24855605
TI  - Diffuse infiltrative primary cardiac lymphoma with delayed extracardiac
      involvement.
AB  - Primary cardiac lymphoma (PCL) is an extremely rare and fatal neoplasm of the
      heart. Traditionally, it is defined as lymphoma involving the heart or
      pericardium. PCL has a poor prognosis because of the diagnostic difficulty and
      its location. We present the case of a 48-year-old man who presented with
      pericardial effusion and diffuse cardiac wall thickening. We first suspected
      infiltrative heart disease. However, even after performing a biopsy, we could not
      establish an accurate diagnosis. After 20 months, primary cardiac diffuse large B
      cell lymphoma (DLBCL) was diagnosed by cervical lymph node biopsy. In this case,
      after chemotherapy, the DLBCL lesions, including cardiac wall thickening,
      improved. The treatment outcome suggests that the diagnosis was diffuse
      infiltrative PCL with delayed extracardiac involvement. 

PMID- 24855606
TI  - Successful endovascular aneurysm repair for abdominal aortic aneurysm in a
      patient with severe coronary artery disease undergoing off-pump coronary artery
      bypass grafting.
AB  - It is well known that patients with abdominal aortic aneurysm (AAA) often have
      concomitant coronary artery disease (CAD). In cases of AAA with severe CAD
      requiring coronary artery bypass grafting (CABG), two therapeutic strategies
      regarding the timing of CABG can be considered: staged or simultaneous
      operations. However, the ideal treatment of patients with large AAA and critical
      CAD remains controversial. We experienced a case of successful endovascular
      aneurysm repair after off-pump CABG in a 70-year-old patient who had a huge AAA
      and critical CAD. 

PMID- 24855607
TI  - Plantar Pressure Distribution During Robotic-Assisted Gait in Post-stroke
      Hemiplegic Patients.
AB  - OBJECTIVE: To assess the plantar pressure distribution during the robotic
      assisted walking, guided through normal symmetrical hip and knee physiological
      kinematic trajectories, with unassisted walking in post-stroke hemiplegic
      patients. METHODS: Fifteen hemiplegic stroke patients, who were able to walk a
      minimum of ten meters independently but with asymmetric gait patterns, were
      enrolled in this study. All the patients performed both the robotic-assisted
      walking (Lokomat) and the unassisted walking on the treadmill with the same body
      support in random order. The contact area, contact pressure, trajectory length of
      center of pressure (COP), temporal data on both limbs and asymmetric index of
      both limbs were obtained during both walking conditions, using the F-Scan in-shoe
      pressure measurement system. RESULTS: The contact area of midfoot and total foot
      on the affected side were significantly increased in robotic-assisted walking as
      compared to unassisted walking (p<0.01). The contact pressure of midfoot and
      total foot on affected limbs were also significantly increased in robotic
      assisted walking (p<0.05). The anteroposterior and mediolateral trajectory length
      of COP were not significantly different between the two walking conditions, but
      their trajectory variability of COP was significantly improved (p<0.05). The
      asymmetric index of area, stance time, and swing time during robotic-assisted
      walking were statistically improved as compared with unassisted walking (p<0.05).
      CONCLUSION: The robotic-assisted walking may be helpful in improving the gait
      stability and symmetry, but not the physiologic ankle rocker function.

PMID- 24855608
TI  - The effect of early neuromuscular electrical stimulation therapy in
      acute/subacute ischemic stroke patients with Dysphagia.
AB  - OBJECTIVE: To compare the outcome of an early application of neuromuscular
      electrical stimulation (NMES) combined with traditional dysphagia therapy (TDT)
      versus traditional dysphagia therapy only in acute/subacute ischemic stroke
      patients with moderate to severe dysphagia by videofluoroscopic swallowing study
      (VFSS). METHODS: Fifty-seven dysphagic stroke patients were enrolled in a VFSS
      within 10 days after stroke onset. Patients were randomly assigned into two
      treatment groups. Thirty-one patients received NMES combined with TDT (NMES/TDT
      group) and 26 patients received TDT only (TDT group). Electrical stimulation with
      a maximal tolerable intensity was applied on both suprahyoid muscles for 30
      minutes, 5 days per week during 3 weeks. The swallowing function was evaluated at
      baseline and 3, 6, and 12 weeks after baseline. Outcomes of the VFSS were
      assessed using the Functional Oral Intake Scale (FOIS). RESULTS: The mean ages
      were 63.5+/-11.4 years in the NMES/TDT group and 66.7+/-9.5 years in the TDT
      group. Both groups showed a significant improvement on the FOIS after treatment.
      The FOIS score was significantly more improved at 3 and 6 weeks after baseline in
      the NMES/TDT group than in the TDT group (p<0.05). CONCLUSION: An early
      application of NMES combined with TDT showed a positive effect in acute/subacute
      ischemic stroke patients with dysphagia. These results indicated that the early
      application of NMES could be used as a supplementary treatment of TDT to help
      rehabilitate acute/subacute dysphagic stroke patients by improving their
      swallowing coordination.

PMID- 24855609
TI  - The effect of virtual reality and tetra-ataxiometric posturography programs on
      stroke patients with impaired standing balance.
AB  - OBJECTIVE: To investigate the effect of virtual reality (VR) and a tetra
      ataxiometric posturography (Tetrax) program on stroke patients with impaired
      standing balance. METHODS: Thirty acute stroke patients with impaired standing
      balance were recruited and randomly assigned to a VR, Tetrax, or control group.
      All patients received conventional balance training as a baseline; and VR and
      Tetrax patients received VR or Tetrax treatment, in addition. The primary outcome
      measures to evaluate the overall standing balance were the Berg Balance Scale
      (BBS) and the falling index (FI). The secondary outcome measures were the
      stability index (SI) and the weight distribution index (WDI), which were used to
      evaluate the balance status according to specific body positions. The FI, SI, and
      WDI were measured using the Tetrax instrument. RESULTS: The BBS and FI scores
      were improved in all groups, with no significant differences between groups. In
      open-eyed positions, the VR group showed significantly greater improvement in SI
      and WDI scores than the control group (p<0.017). In closed-eyed positions, the
      Tetrax group showed significantly greater improvement in SI and WDI scores than
      the control group (p<0.017). CONCLUSION: The inclusion of VR and Tetrax programs
      did not lead to an overall benefit in balance. VR and Tetrax did, however,
      demonstrate a benefit in specific positions. A Tetrax program may benefit
      patients with abnormal proprioceptive function, whereas a VR program may benefit
      patients with normal sensory function.

PMID- 24855610
TI  - The Comparison of Effects of Suprascapular Nerve Block, Intra-articular Steroid
      Injection, and a Combination Therapy on Hemiplegic Shoulder Pain: Pilot Study.
AB  - OBJECTIVE: To assess the relative effectiveness of three injections methods
      suprascapular nerve block (SSNB) alone, intra-articular steroid injection (IAI)
      alone, or both-on relief of hemiplegic shoulder pain. METHODS: We recruited 30
      patients with hemiplegic shoulder pain after stroke. SSNB was performed in 10
      patients, IAI in 10 patients, and a combination of two injections in 10 patients.
      All were ultrasonography guided. Each patient's maximum passive range of motion
      (ROM) in the shoulder was measured, and the pain intensity level was assessed
      with a visual analogue scale (VAS). Repeated measures were performed on pre
      injection, and after injection at 1 hour, 1 week, and 1 month. Data were analyzed
      by Kruskal-Wallis and Friedman tests. RESULTS: All variables that were repeatedly
      measured showed significant differences in shoulder ROM with time (p<0.05), but
      there was no difference according injection method. In addition, VAS was
      statistically significantly different with time, but there was no difference by
      injection method. Pain significantly decreased until a week after injection, but
      pain after a month was relatively increased. However, pain was decreased compared
      to pre-injection. CONCLUSION: The three injection methods significantly improved
      shoulder ROM and pain with time, but no statistically significant difference was
      found between them.

PMID- 24855612
TI  - Comparison of the using ability between a smartphone and a conventional mobile
      phone in people with cervical cord injury.
AB  - OBJECTIVE: To investigate the ability of spinal cord injury (SCI) patients in the
      use mobile cellular devices, especially the smartphone. METHODS: Seventeen people
      with motor complete cervical SCI participated in the study. The assist-devices
      deemed most fitting were introduced to the patients: a mouth stick,
      multifunctional splint, activities of daily living (ADL) splint, universal cuff
      or none of the above. To determine the effective devices, a Multi-Directional
      Click Test (MDCT), Phone Number Test (PNT), and individual satisfaction inquiry
      were used. The most appropriate assist device was selected by MDCT. Subsequently
      PNT and individual satisfaction inquiry were performed with the conventional
      model and compared. RESULTS: Those with C4 cord injury chose mouth stick. Those
      with C5 cord injury chose multifunctional splint (3 people) and ADL splint (2
      people). Those with C6 cord injury chose universal cuff (3 people) or bare hands
      only. Those with C7 cord injury chose universal cuff (3 people). With a
      smartphone, all participants were able to complete the PNT. With a conventional
      model, only twelve participants (71%) were able to complete the same test. While
      it took 26.8+/-6.8 seconds with a conventional model to complete PNT, the same
      test took 18.8+/-10.9 seconds to complete with a smartphone (p<0.05). Overall,
      participants expressed higher satisfaction when using a smartphone. CONCLUSION:
      The results offer a practical insight into the appropriate assist devices for SCI
      patients who wish to use mobile cellular devices, particularly smartphones. When
      the SCI patients are given the use of a smartphone with the appropriate assist
      devices, the SCI patients are expected to access mobile cellular device faster
      and with more satisfaction.

PMID- 24855611
TI  - Access to medical services in korean people with spinal cord injury.
AB  - OBJECTIVE: To investigate the accessibility of medical services for Korean people
      with spinal cord injury (SCI) compared to the control group (CG) and to evaluate
      significantly related factors. METHODS: A total of 363 community dwelling people
      with chronic SCI were enrolled and 1,089 age- and sex-matched subjects were
      randomly selected from the general population as the CG. Self-reported access to
      medical services was measured by asking "Have you experienced the need for a
      hospital visit in the last year but could not?". This was followed up by asking
      the reasons for not receiving services when medically necessary. Variables,
      including lack of finances, difficulties making medical appointments, and lack of
      transportation were evaluated for accessibility to medical services. RESULTS:
      Sixty subjects (16.5%) in the SCI group had difficulties receiving medical
      services due to a lack of accessibility, compared to 45 (4.1%) in the CG
      (p<0.001). Variables causing difficulties receiving medical services were lack of
      transportation (27 persons, 45%), lack of finances (24 persons, 40%), and
      difficulty scheduling hospital appointments (9 persons, 15%) in the SCI group. In
      the CG, availability (lack of available time) and acceptability (deciding not to
      visit the hospital due to mild symptoms) were the reasons for not receiving
      medical care. CONCLUSION: People with SCI experienced limited accessibility to
      medical services, which was due to environmental rather than personal factors
      compared to that in the CG. Therefore, development of social policies to reduce
      or remove environmental variables is necessary.

PMID- 24855613
TI  - Neuroradiological and neurophysiological characteristics of patients with
      dyskinetic cerebral palsy.
AB  - OBJECTIVE: To investigate neuroradiological and neurophysiological
      characteristics of patients with dyskinetic cerebral palsy (CP), by using
      magnetic resonance imaging (MRI), voxel-based morphometry (VBM), diffusion tensor
      tractography (DTT), and motor evoked potential (MEP). METHODS: Twenty-three
      patients with dyskinetic CP (13 males, 10 females; mean age 34 years, range 16-50
      years) were participated in this study. Functional evaluation was assessed by the
      Gross Motor Functional Classification System (GMFCS) and Barry-Albright Dystonia
      Scale (BADS). Brain imaging was performed on 3.0 Tesla MRI, and volume change of
      the grey matter was assessed using VBM. The corticospinal tract (CST) and
      superior longitudinal fasciculus (SLF) were analyzed by DTT. MEPs were recorded
      in the first dorsal interossei, the biceps brachii and the deltoid muscles.
      RESULTS: Mean BADS was 16.4+/-5.0 in ambulatory group (GMFCS levels I, II, and
      III; n=11) and 21.3+/-3.9 in non-ambulatory group (GMFCS levels IV and V; n=12).
      Twelve patients showed normal MRI findings, and eleven patients showed abnormal
      MRI findings (grade I, n=5; grade II, n=2; grade III, n=4). About half of
      patients with dyskinetic CP showed putamen and thalamus lesions on MRI. Mean BADS
      was 20.3+/-5.7 in normal MRI group and 17.5+/-4.0 in abnormal MRI group. VBM
      showed reduced volume of the hippocampus and parahippocampal gyrus. In DTT, no
      abnormality was observed in CST, but not in SLF. In MEPs, most patients showed
      normal central motor conduction time. CONCLUSION: These results support that
      extrapyramidal tract, related with basal ganglia circuitry, may be responsible
      for the pathophysiology of dyskinetic CP rather than CST abnormality.

PMID- 24855614
TI  - Comparison of treatment effects between children with spastic cerebral palsy
      under and over five years after botulinum toxin type a injection.
AB  - OBJECTIVE: To evaluate whether age influences a change in the spasticity of the
      ankle plantar flexor after botulinum toxin type A (BTA) injection in children
      with spastic cerebral palsy (CP). METHODS: Sixteen children with spastic CP were
      enrolled in the study. Seven children (group 1) were under 5 years of age, and
      nine (group 2) were over 5 years of age. They all received BTA injection in the
      gastrocnemius muscle (GCM) under ultrasound guidance. Passive range of motion
      (PROM) of ankle dorsiflexion, Modified Ashworth Scale (MAS) of the ankle plantar
      flexor, Gross Motor Function Measure (GMFM) and median red pixel intensity (RPI)
      of the medial GCM on real-time sonoelastography were measured at baseline (pre
      injection) and 1-, 3-, and 6-month post-injection. RESULTS: In both groups, the
      mean PROM, MAS, and RPI were significantly improved after injection until 6-month
      post-injection. The change of PROM of ankle dorsiflexion in group 1 was
      significantly greater than that in group 2, until 6-month post-injection. The
      change in the MAS and GMFM between baseline and 6-month post-injection in group 1
      was greater than that in group 2. The changes in the median RPI between baseline
      and 3- and 6-month post-injections were greater in group 1 than in group 2.
      CONCLUSION: Our pilot study demonstrated the different changes in spasticity of
      the ankle plantar flexor after BTA injection based on age. Therefore, age may be
      considered when establishing a treatment plan using BTA injection for children
      with spastic CP.

PMID- 24855615
TI  - Two-year outcomes of deep brain stimulation in adults with cerebral palsy.
AB  - OBJECTIVE: To investigate the effect of deep brain stimulation (DBS) on reducing
      dystonia and disability in adults with cerebral palsy (CP) and to compare the
      therapeutic outcomes between primary dystonia patients and CP patients over two
      years after bilateral pallidal DBS. METHODS: Five patients with primary dystonia
      and seven CP patients with dystonia were recruited. All subjects received DBS
      surgery in both globus pallidus. Burke-Fahn-Marsden dystonia rating scale
      consisting of dystonia movement score and disability score and subjective
      satisfaction scale were assessed after 1 month and every 6 months over two years
      following DBS treatment. RESULTS: On the dystonia movement scale, both groups of
      primary dystonia patients and CP patients showed a significant decrease over time
      following DBS. On the disability scale, patients with primary dystonia showed a
      significant decrease over time, whereas the disability score of CP patients did
      not change over the two years. Comparing the dystonia movement and disability
      scores of CP patients at each assessment, patients with primary dystonia showed a
      significant reduction after 6 months. Comparing the satisfaction scores of CP
      patients after DBS, patients with primary dystonia showed significantly higher
      subjective satisfaction. CONCLUSION: Whereas dystonia can be significantly
      reduced in patients with primary dystonia, CP patients showed a modest
      improvement on the dystonia movement scale, but not on the disability scale.
      Therefore, DBS may be considered with caution as a treatment modality of CP
      patients with dystonia.

PMID- 24855616
TI  - The therapeutic effect of tibia counter rotator with toe-out gait plate in the
      treatment of tibial internal torsion in children.
AB  - OBJECTIVE: To evaluate the therapeutic effect of a Tibia Counter Rotator (TCR)
      with toe-out gait plate (GP) upon tibial internal torsion by a comparative
      analysis of transmalleolar angle (TMA) and gait analysis with GP alone. METHODS:
      Twenty participants with tibial internal torsion were recruited for this study.
      Each 10 participants were included in group A with TCR and GP application and in
      group B with GP application only. The TMA and the kinematic results were used for
      the evaluation of the therapeutic effects of orthoses. RESULTS: Within each
      group, TMA showed a significant increase after treatment. Group A showed a
      continuous improvement up to six months, however, group B showed an improvement
      up to five months only. Group A showed a significantly higher correction effect
      than group B after treatment. Regarding kinematic data, both groups showed a
      significantly decreased mean ankle adduction angle after treatment. However,
      group A showed a significantly lower mean ankle adduction angle than group B
      after six months. CONCLUSION: The group with TCR and GP showed a significantly
      better outcome and continued correction force compared to the group with GP only.
      Our results suggest that TCR with GP may be useful therapeutic orthoses for
      children with tibial internal torsion.

PMID- 24855617
TI  - Difference of diagnostic rates and analytical methods in the test positions of
      vestibular evoked myogenic potentials.
AB  - OBJECTIVE: To compare the differences of diagnostic rates, of the two widely used
      test positions, in measuring vestibular evoked myogenic potentials (VEMP) and
      selecting the most appropriate analytical method for diagnostic criteria for the
      patients with vertigo. METHODS: Thirty-two patients with vertigo were tested in
      two comparative testing positions: turning the head to the opposite side of the
      evaluating side and bowing while in seated position, and bowing while in supine
      positions. Abnormalities were determined by prolonged latency of p13 or n23,
      shortening of the interpeak latency, and absence of VEMP formation. RESULTS:
      Using the three criteria above for determining abnormalities, both the seated and
      supine positions showed no significant differences in diagnostic rates, however,
      the concordance correlation of the two positions was low. When using only the
      prolonged latency of p13 or n23 in the two positions, diagnostic rates were not
      significantly different and their concordance correlation was high. On the other
      hand, using only the shortened interpeak latency in both positions showed no
      significant difference of diagnostic rates, and the degree of agreement between
      two positions was low. CONCLUSION: Bowing while in seated position with the head
      turned in the opposite direction to the area being evaluated is found to be the
      best VEMP test position due to the consistent level of sternocleidomastoid muscle
      tension and the high level of compliance. Also, among other diagnostic analysis
      methods, using prolonged latency of p13 or n23 as the criterion is found to be
      the most appropriate method of analysis for the VEMP test.

PMID- 24855618
TI  - Trunk muscles strength as a risk factor for nonspecific low back pain: a pilot
      study.
AB  - OBJECTIVE: To investigate the effects of asymptomatic back muscle weakness and
      spinal deformity on low back pain (LBP). METHODS: Sixty healthy subjects without
      LBP participated in this study. Radiography and an isokinetic/isometric
      dynamometer were used to respectively measure spinal scoliosis/lordosis and the
      strength of the trunk flexors/extensors. After 2 years, 48 subjects visited the
      hospital again and LBP episodes, its severity and the Korean version of the
      Oswestry Disability Index were assessed. Differences between the group with LBP
      and the group without LBP were evaluated and the association with LBP incidence
      and severity was determined. RESULTS: Sex, age, and trunk strength were
      significantly different in both group. Sex and age were significantly positive
      associated with LBP incidence. The isometric trunk flexor and extensor strength,
      maximum isokinetic trunk flexor and extensor strength were significantly and
      negatively associated with the LBP severity. The maximum isokinetic trunk
      extensor and maximum isometric trunk extensor strength was significantly negative
      associated with the LBP incidence. CONCLUSION: LBP incidence is associated with
      isometric and isokinetic trunk extensor weakness, whereas LBP severity is
      associated with age, sex, isokinetic trunk extensor and flexor weakness,
      isometric trunk extensor and flexor weakness.

PMID- 24855619
TI  - Short-term change of handgrip strength after trigger point injection in women
      with muscular pain in the upper extremities.
AB  - OBJECTIVE: To determine overall handgrip strength (HGS), we assessed the short
      term change of HGS after trigger point injection (TPI) in women with muscular
      pain in the upper extremities by comparison with established pain scales.
      METHODS: The study enrolled 50 female patients (FMS with MPS group: 29 patients
      with combined fibromyalgia [FMS] and myofascial pain syndrome [MPS]; MPS group:
      21 patients with MPS) who presented with muscular pain in the upper extremities
      at Konyang University Hospital. In addition, a total of 9 healthy women (control
      group) were prospectively enrolled in the study. We surveyed the three groups
      using the following established pain scales: the Fibromyalgia Impact
      Questionnaire (FIQ), the 36-Item Short Form Health Survey (SF-36), and the Short
      Form McGill Pain Questionnaire (MPQ). HGS was measured in both hands of study
      participants using a handgrip dynamometer. We performed TPI (0.5% lidocaine,
      total 10 mL, injected at the pain site of upper extremities). After 20 minutes,
      we remeasured the patient's HGS and MPQ score. RESULTS: ANOVA analysis was
      conducted among groups. Based on Tukey multiple comparison test, the majority of
      FIQ and SF-36 subscales, total FIQ and SF-36 scores, MPQ and HGS were
      significantly different between FMS with MPS and the other groups. There was no
      statistically significant difference between MPS and control groups. Higher HGS
      was positively associated with enhanced physical function, negatively associated
      with total FIQ and MPQ scores, and positively associated with the total SF-36
      score calculated using Spearman correlation. Post-TPI MPQ decreased and HGS
      increased. In patient groups, a negative correlation was found between MPQ and
      HGS. CONCLUSION: The HGS test might potentially be a complementary tool in
      assessing the short-term treatment effects of women with muscular pain in the
      upper extremities.

PMID- 24855620
TI  - Assessment of peripheral neuropathy in patients with rheumatoid arthritis who
      complain of neurologic symptoms.
AB  - OBJECTIVE: To assess the prevalence of peripheral neuropathy in patients with
      rheumatoid arthritis (RA) having neuropathic symptoms, and to investigate the
      relationship between electrophysiological findings of peripheral neuropathy and
      clinical findings of RA. METHODS: Patients with a clinical diagnosis of RA and
      who had tingling or burning sensation in any extremity were
      electrophysiologically examined for evidence of peripheral neuropathy. Study
      parameters, including age, gender, laboratory parameters, duration of RA, and
      medication, were recorded. The symptoms and signs of neuropathy were quantified
      with the neuropathy symptom score, and the functional statuses of these patients
      were assessed. RESULTS: Out of a total of 30 RA patients, 10 (33%) had peripheral
      neuropathy: 2 had bilateral carpal tunnel syndrome (CTS), 5 had unilateral CTS, 1
      had sensory polyneuropathy, and 2 had motor-sensory polyneuropathy. The mean ages
      of the patients with and without peripheral neuropathy were 69.4 and 56.5 years,
      respectively (p<0.05). A significant relationship was found between peripheral
      neuropathy and anti-cyclic citrullinated peptide (anti-CCP) antibody. However, no
      relationship was found between peripheral neuropathy and the type of medication,
      RA duration, the patients' functional status, neuropathic symptoms, erythrocyte
      sedimentation rate, and C-reactive protein values. CONCLUSION: Neuropathic
      symptoms are common in RA patients, and it is difficult to distinguish peripheral
      neuropathy symptoms from those of arthritis. Patients with RA, particularly
      elderly patients and anti-CCP antibody positive patients who complain of
      neuropathic symptoms should undergo electrophysiological examination.

PMID- 24855622
TI  - Concomitant occurrence of cervical myelopathy, cerebral infarction, and
      peripheral neuropathy in systemic lupus erythematosus: a case report.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease
      characterized by multiorgan involvement with diverse clinical presentations.
      Central nervous system involvement in neuropsychiatric syndromes of SLE (NPSLE),
      such as cerebrovascular disease and myelopathy, is a major cause of morbidity and
      mortality in SLE patients. The concomitant occurrence of myelopathy,
      cerebrovascular disease, and peripheral neuropathy in a patient with SLE has not
      yet been reported. We report on a 41-year-old woman with SLE who showed motor and
      sensory impairment with urinary retention and was diagnosed with cervical
      myelopathy and acute cerebral infarction by spine and brain magnetic resonance
      imaging and peripheral neuropathy by electrodiagnostic examination. Even though
      pathogenesis of NPSLE is not well elucidated, we assume that increased antibodies
      of anti-double stranded DNA (anti-dsDNA), presence of lupus anticoagulant and
      hypertension are risk factors that have caused neuropsychiatric lupus in this
      patient. 

PMID- 24855623
TI  - Central hyperthermia treated with baclofen for patient with pontine hemorrhage.
AB  - Central hyperthermia is a very rare disease; however, once it happens, it is
      associated with a poor prognosis and high mortality for patients with severe
      brainstem strokes. Following a pontine hemorrhage, a 46-years-old female
      developed prolonged hyperthermia. Work-ups to the fever gave no significant clues
      for the origin of fever, and hyperthermia did not respond to any empirical
      antibiotics or antipyretic agents. The patient's body temperature still
      fluctuated in a range of 37.5C to 39.2C. Considering the lesion of hemorrhage, we
      suspected central hyperthermia rather than infectious diseases. We started with
      baclofen administration at a dose of 30 mg/day. The body temperature changed to a
      range of 36.6C to 38.2C. We raised the dose of baclofen to 60 mg/day. The
      patient's body temperature finally dropped to a normal range. Central
      hyperthermia, caused by failures of thermoregulatory pathways in brainstem,
      following the pontine hemorrhage rarely occurs. Baclofen can be used to treat
      suspected central hyperthermia in a patient with pontine hemorrhage. 

PMID- 24855621
TI  - Impact of exercise-based cardiac rehabilitation on de novo coronary lesion in
      patients with drug eluting stent.
AB  - OBJECTIVE: To compare the rate of progression of de novo lesion between the
      cardiac rehabilitation (CR) and control groups. METHODS: This is a retrospective
      observational study. Patients who received drug-eluting stent (DES) due to acute
      coronary syndrome were included as subjects. The CR group received eight weeks of
      early CR program, and sustained a self-exercise program in the homes. The control
      group was instructed to exercise independently. Nine months after the first
      insertion of DES, we implemented follow-up coronary angiography, and compared the
      rate of progression of de novo lesion by quantitative angiographic measurement
      between the two groups. RESULTS: A total of 81 patients were recruited as
      subjects to CR group (n=32) or control group (n=49). At nine months, late luminal
      loss was 0.04+/-0.23 mm in the CR group and 0.00+/-0.31 mm in the control group
      (p=0.54, observed power=0.10). Late loss was -0.90%+/-9.53% in the CR group and
      0.80%+/-11.15% in the control group (p=0.58, observed power=0.05). No target
      lesion revascularization procedures were needed in the CR group, while two in the
      control group (p=0.25). In the CR group, mean VO2max was significantly improved
      from 24.36+/-5.00 to 27.68+/-5.24 mL/kg/min (p<0.001). CONCLUSION: We could not
      observe a statistically significant difference in the progression rate of de novo
      lesion between the CR and control groups. Thus the current amount of nine months
      exercise-based CR program does not seem to have a distinct impact on the
      retardation of de novo coronary lesion in patients who received percutaneous
      coronary intervention with DES.

PMID- 24855624
TI  - Inexplicable Abdominal Pain due to Thoracic Spinal Cord Tumor.
AB  - Chronic, refractory abdominal pain without a metabolic or structural
      gastroenterological etiology can be challenging for diagnosis and management.
      Even though it is rare, it has been reported that such a recurrent abdominal pain
      associated with radicular pattern can be derived from structural neurologic
      lesion like spinal cord tumor. We experienced an unusual case of chronic
      recurrent abdominal pain that lasted for two years without definite neurologic
      deficits in a patient, who has been harboring thoracic spinal cord tumor. During
      an extensive gastroenterological workup for the abdominal pain, the spinal cord
      tumor had been found and was resected through surgery. Since then, the
      inexplicable pain sustained over a long period of time eventually resolved. This
      case highlights the importance of taking into consideration the possibility of
      spinal cord tumor in differential diagnosis when a patient complains of chronic
      and recurrent abdominal pain without other medical abnormalities. 

PMID- 24855625
TI  - Neurological complication after low-voltage electric injury: a case report.
AB  - Electrical shock can result in neurological complications, involving both
      peripheral and central nervous systems, which may present immediately or later
      on. However, delayed neurological complications caused by low-voltage electric
      shock are rarely reported. Here, a case of a man suffering from weakness and
      aphasia due to the delayed-onset of the peripheral nerve injury and ischemic
      stroke following an electrical shock is presented. Possible mechanisms underlying
      the neurological complications include thermal injury to perineural tissue,
      overactivity of the sympathetic nervous system, vascular injury, and histological
      or electrophysiological changes. Moreover, vasospasms caused by low-voltage
      alternating current may predispose individuals to ischemic stroke. Therefore,
      clinicians should consider the possibility of neurological complications, even if
      the onset of the symptoms is delayed, and should perform diagnostic tests, such
      as electrophysiology or imaging, when patients present with weakness following an
      electric injury. 

PMID- 24855626
TI  - Median nerve injury caused by brachial plexus block for carpal tunnel release
      surgery.
AB  - Carpal tunnel release is required to treat patients with severe carpal tunnel
      syndrome. The regional anesthesia of the upper limb by brachial plexus block
      (BPB) may be a good alternative to general anesthesia for carpal tunnel release
      surgery, because it results in less complications. However, the regional
      anesthesia still has various side effects, such as hematoma, infection, and
      peripheral neuropathy. We hereby report a rare case of median nerve injury caused
      by BPB for carpal tunnel release. 

PMID- 24855627
TI  - Magnetic resonance neurographic findings in classic idiopathic neuralgic
      amyotrophy in subacute stage: a report of four cases.
AB  - Neuralgic amyotrophy (NA) is characterized by acute onset of severe pain,
      followed by muscular weakness and wasting of the shoulder girdle. While the
      diagnosis of NA mainly relies on the clinical history and examination, some
      investigations including electrophysiologic study and radiologic study may help
      to confirm the diagnosis. Magnetic resonance neurography (MRN), a new technique
      for the evaluation of peripheral nerve disorders, can be helpful in the diagnosis
      of NA. MRN presents additional benefits in comparison to conventional magnetic
      resonance imaging in the diagnosis of idiopathic NA (INA). In this report, we
      present the first four cases of classic INA diagnosed with MRN in subacute stage.
      MRN imaging modality should be considered in patients clinically suspected of
      INA. 

PMID- 24855628
TI  - Ullrich Congenital Muscular Dystrophy Possibly Related With COL6A1 p.Gly302Arg
      Variant.
AB  - Ullrich congenital muscular dystrophy (UCMD) is characterized by congenital
      weakness, proximal joint contractures, and hyperlaxity of distal joints. UCMD is
      basically due to a defect in extra cellular matrix protein, collagen type VI. A
      37-year-old woman who cannot walk independently visited our outpatient clinic.
      She had orthopedic deformities (scoliosis, joint contractures, and distal joint
      hyperlaxity), difficulty of respiration, and many skin keloids. Her hip computed
      tomography showed diffuse fatty infiltration and the 'central shadow' sign in
      thigh muscles. From the clinical information suggesting collagen type VI related
      muscle disorder, UCMD was highly considered. COL6A1 gene sequencing confirmed
      this patient as UCMD with novel c.904G>A (p.Gly302Arg) variant. If
      musculoskeletal and dermatologic manifestations and radiologic findings imply
      abnormalities in collagen type VI network, COL6A related congenital muscular
      dystrophy was to be suspected. 

PMID- 24855630
TI  - Association between dietary intake and seasonal variations in postmenopausal
      women.
AB  - BACKGROUND: Evidence supports that increasing number of postmenopausal women are
      suffering from one or more chronic diseases. Dietary patterns have a pivotal role
      in maintaining human health. The aim of this study was to characterize the
      nutrients and energy intake in postmenopausal women, with the special focus on
      seasonal variation effect in their food intake. METHODS: The study population
      consisted of 30 postmenopausal women referred to Dr. Shariati Hospital, Tehran
      (Iran). Socio-demographic characteristics and BMI were registered. Dietary
      assessment was performed by a 3 day food records in each season through one year,
      allowing the estimation of energy, protein, carbohydrate, total fat,
      monounsaturated fatty acid (MUFA), polyunsaturated fatty acids (PUFA) and
      saturated fatty acids (SFA) intake. The mean of nutrient intake in each season
      was adjusted for energy intake. The effect of season on energy and nutrients
      intake was assessed based on the General linear model (GLM). RESULTS: The mean of
      daily intake of vitamin C, B, B2, B12, iron, zinc, phosphorus and chromium was
      significantly higher than Recommended Dietary Allowance (RDAs ) (p < 0.05). The
      mean of vitamin D, E, B6, B5, folate, calcium, magnesium, potassium and selenium
      consumption was significantly less than RDAs (p < 0.05). All the participants
      meet the goal for vitamins A, K and B3 from food. The mean of energy intake was
      not different between seasons. However, the mean intake of fat, vitamin C,
      vitamin K and folate was significantly different between seasons. CONCLUSION:
      These findings highlight some nutrients deficiency in postmenopausal women and
      therefore suggest nutritional education with emphasis on seasonal variation
      effect.

PMID- 24855629
TI  - Modulation of de novo purine biosynthesis leads to activation of AMPK and results
      in improved glucose handling and insulin sensitivity.
AB  - BACKGROUND: AMP activated protein kinase (AMPK) regulates key metabolic reactions
      and plays a major role in glucose homeostasis. Activating the AMPK is considered
      as one of the potential therapeutic strategies in treating type-2 diabetes.
      However, targeting AMPK by small molecule mediated approach can be challenging
      owing to diverse isoforms of the enzyme and their varied combination in different
      tissues. In the current study we employ a novel strategy of achieving AMPK
      activation through increasing the levels of cellular AMP (an allosteric activator
      of AMPK) levels by activating the enzyme involved in AMP biosynthesis namely
      Adenylosuccinate lyase (ADSL). METHODS: Rat primary hepatocytes were cultured
      under metabolic overload conditions (500 MUM palmitate) to induce insulin
      resistance. ADSL was overexpressed in these hepatocytes and its effect on hepatic
      glucose output, and triglyceride accumulation was checked. In addition to this,
      ADSL was overexpressed in high fat diet induced obese mice by hydrodynamic tail
      vein injection and its effect on fasting glucose, glucose tolerance and pyruvate
      tolerance were checked. RESULTS: Rat primary hepatocytes when cultured under
      metabolic overload conditions developed insulin resistance as measured in terms
      of failure of insulin to suppress the glucose output. Overexpressing the ADSL in
      these hepatocytes resulted in increased AMPK phosporylation and improved the
      insulin sensitivity and also resulted in reduced triglyceride accumulation and
      inflammatory cytokine levels. In addition to this, when ADSL was overexpressed in
      high fat diet induced obese mice, it resulted in reduced the fasting
      hyperglycemia (20% reduction), and increased glucose and pyruvate tolerance.
      CONCLUSIONS: This study indicates that activating ADSL can be a potential
      mechanism to achieve the activation of AMPK in the cells. This leads to a novel
      idea of exploring the purine nucleotide metabolic pathway as a promising
      therapeutic target for diabetes and metabolic syndrome.

PMID- 24855631
TI  - Weight-related disparities for transgender college students.
AB  - OBJECTIVE: The objective of this study was to explore disparities in weight and
      weight-related behaviors by transgender identity. METHODS: Cross-sectional
      regression models were fit using 2007-2011 College Student Health Survey data.
      RESULTS: Compared to non-transgender, transgender subjects (N=53) were more
      likely to be either underweight [adjusted relative risk (95% CI): 4.78 (1.61
      14.18)] or obese [2.45 (1.21-4.93)], and less likely to meet recommendations for
      strenuous physical activity [1.16 (1.01-1.34)], strengthening physical activity
      [1.32 (1.11-1.56)], and screen time [1.20 (1.02-1.41)]. CONCLUSIONS: More
      research is needed to understand the unique social contexts of transgender
      college students with regard to weight status, physical activity, and screen time
      in order to effectively inform intervention and policy development and
      implementation.

PMID- 24855632
TI  - Enhancing the Potency of F508del Correction: A Multi-Layer Combinational Approach
      to Drug Discovery for Cystic Fibrosis.
AB  - With better understanding of the cellular and molecular pathophysiology
      underlying cystic fibrosis (CF), novel drugs are being developed that
      specifically target the molecular defects of the cystic fibrosis transmembrane
      conductance regulator (CFTR), a cAMP-activated chloride channel on the plasma
      membrane that causes CF. Starting with cell-based high-throughput screening,
      small molecules have been identified that are able to fix specific molecular
      defects of various disease-causing CFTR mutants. With the successful development
      of ivacaftor, a "potentiator" that enhances CFTR chloride channel activity, new
      types of small-molecule compounds that "correct" the misfolding and misprocessing
      of the most common CF-causing mutation, F508del, are actively being sought for.
      Recent studies focused on the potential mechanisms of action of some of the
      investigational CFTR "correctors" shed new light on how the F508del mutant can be
      targeted in an attempt to ameliorate the clinical symptoms associated with CF. A
      multi-layer combinational approach has been proposed to achieve the high-potency
      correction necessary for significant clinical outcome. The mechanistic insights
      obtained from such studies will shape the future therapeutics development for the
      vast majority of CF patients.

PMID- 24855636
TI  - A single chain magnet involving hexacyanoosmate.
AB  - The first single chain magnet (SCM) based on orbitally degenerate
      hexacyanoosmate(III) was prepared. The high values of energy barriers for the
      [Mn(acacen)Os(CN)6](2-) complex of 81 and 48.4 K are the result of interplay of
      three axes anisotropic coupling of [Os(CN)6](3-) with zero field splitted Mn(3+).

PMID- 24855634
TI  - Roles of Iroquois Transcription Factors in Kidney Development.
AB  - Congenital anomalies of the kidney and urinary tract (CAKUT) affect 1/500 live
      births. CAKUT lead to end stage renal failure in children, and are associated
      with high morbidity rates. Understanding the mechanisms of kidney development,
      and that of other associated urogenital tissues, is crucial to the prevention and
      treatment of CAKUT. The kidney arises from self-renewing mesenchymal renal stem
      cells that produce nephrons, which are the principal functional units of the
      organ. To date, the genetic and cellular mechanisms that control nephrogenesis
      have remained poorly understood. In recent years, developmental studies using
      amphibians and zebrafish have revealed that their simple embryonic kidney, known
      as the pronephros, is a useful paradigm for comparative studies of nephron
      ontogeny. Here, we discuss the new found roles for Iroquois transcription factors
      in pronephric nephron patterning, and explore the relevance of these findings for
      kidney development in humans.

PMID- 24855635
TI  - A novel electrochemical method to determine alpha-amylase activity.
AB  - In this paper, we report a novel electrochemical method that can be developed as
      a biosensor for simple and direct determination of alpha-amylase activity. The
      method is based on the hydrolysis of maltopentaose, the substrate of the enzyme,
      which is immobilized on the surface of a gold electrode, and the induced charge
      changes of the substrate-modified electrode. Specifically, the substrate
      maltopentaose is immobilized onto a gold electrode surface via a simple and
      direct immobilization technique that involves a one-step and site-specific
      attachment of unmodified maltopentaose to the hydrazide-derivatized surface. So,
      by analyzing the electrochemical signal obtained from the electro-active molecule
      [Ru(NH3)5Cl](2+) during the hydrolysis of maltopentaose, the determination of
      alpha-amylase activity is achieved. Under optimized conditions, alpha-amylase
      activity can be assayed with a detection limit of 0.022 U mL(-1). The biosensor
      exhibits a rapid response, good stability and anti-interference ability.
      Furthermore, the biosensor has also been successfully applied to detect alpha
      amylase in human serum, which shows acceptable accuracy compared to the currently
      used clinical method. The proposed method in this work may also have potential
      application of alpha-amylase determination in real blood samples, diagnostics and
      food production in the future. 

PMID- 24855633
TI  - White Matter and Cognitive Changes in Veterans Diagnosed with Alcoholism and
      PTSD.
AB  - Alcoholism frequently occurs in returning U.S. Veterans, and is often comorbid
      with Post Traumatic Stress Disorder (PTSD). The goal of this study was to
      investigate the relationship between white matter changes and neuropsychological
      alterations in Operation Enduring Freedom, and/or Operation Iraqi Freedom
      (OEF/OIF) alcoholic Veterans with two primary aims: (1) to examine the
      relationship of alcoholism to brain structure and function while controlling for
      the potential effects of comorbid PTSD, and (2) to examine whether the effects of
      alcoholism are moderated by the quantity of lifetime alcohol consumption. Our
      sample consisted of 71 deployed OEF/OIF Veterans stratified into four groups:
      alcoholics without PTSD, alcoholics with PTSD, participants with PTSD without
      comorbid alcoholism, and control participants without alcoholism or PTSD.
      Participants were given an extensive neuropsychological and psychiatric
      assessment battery, as well as Magnetic Resonance Diffusion Tensor Imaging (DT
      MRI) scans. Results showed that disruption of executive functioning, and abnormal
      fractional anisotropy (FA; a measure of axonal integrity) within the frontal
      subcortical and dorsolateral frontal-parietal regions, occurred independently of
      the effects of PTSD. Furthermore, these cognitive and neuronal alterations were
      unique to the most severe subgroup of alcoholics who consumed the greatest amount
      of alcohol over the course of their lifetime, as compared to the rest of the
      sample. Axonal integrity within this subgroup, in regions underlying the frontal
      subcortical area, was shown to be decreased independently of cognitive changes.
      Integrity of axons underlying the dorsolateral frontal-parietal region, however,
      was increased. We hypothesized that this is a compensatory mechanism for
      executive dysfunction.

PMID- 24855637
TI  - Ligand field density functional theory for the prediction of future domestic
      lighting.
AB  - We deal with the computational determination of the electronic structure and
      properties of lanthanide ions in complexes and extended structures having open
      shell f and d configurations. Particularly, we present conceptual and
      methodological issues based on Density Functional Theory (DFT) enabling the
      reliable calculation and description of the f -> d transitions in lanthanide
      doped phosphors. We consider here the optical properties of the Pr(3+) ion
      embedded into various solid state fluoride host lattices, for the prospection and
      understanding of the so-called quantum cutting process, being important in the
      further quest of warm-white light source in light emitting diodes (LED). We use
      the conceptual formulation of the revisited ligand field (LF) theory, fully
      compatibilized with the quantum chemistry tools: LFDFT. We present methodological
      advances for the calculations of the Slater-Condon parameters, the ligand field
      interaction and the spin-orbit coupling constants, important in the non-empirical
      parameterization of the effective Hamiltonian adjusted from the ligand field
      theory. The model shows simple procedure using less sophisticated computational
      tools, which is intended to contribute to the design of modern phosphors and to
      help to complement the understanding of the 4f(n) -> 4f(n-1)5d(1) transitions in
      any lanthanide system. 

PMID- 24855638
TI  - Introducing [Mn(CO)3(tpa-kappa(3)N)](+) as a novel photoactivatable CO-releasing
      molecule with well-defined iCORM intermediates - synthesis, spectroscopy, and
      antibacterial activity.
AB  - [Mn(CO)3(tpa-kappa(3)N)]Br was prepared as a novel photoactivatable CO-releasing
      molecule (PhotoCORM) from [MnBr(CO)5] and tris(2-pyridylmethyl)amine (tpa) for
      the delivery of carbon monoxide to biological systems, with the kappa(3)N binding
      mode of the tetradentate tpa ligand demonstrated by X-ray crystallography. The
      title compound is a CORM prodrug stable in solution in the dark for up to 16 h.
      However, photoactivation at 365 nm leads to CO release from the metal
      coordination sphere and transfer to haem proteins, as demonstrated by the
      standard myoglobin assay. Different iCORM intermediates could be detected with
      solution IR spectroscopy and assigned using DFT vibrational calculations. The
      antibacterial activity of the complex was studied on Escherichia coli. No effects
      were observed when the cultures were either kept in the dark in the presence of
      PhotoCORM or illuminated in the absence of metal complex. However,
      photoactivation of [Mn(CO)3(tpa-kappa(3)N)]Br at 365 nm led to the appearance of
      the spectral signatures of CO-coordinated haems in the terminal oxidases of the
      bacterial electron transport chain in whole-cell UV/Vis absorption spectra.
      Significant internalization of the PhotoCORM was demonstrated by ICP-MS
      measurement of the intracellular manganese concentration. In particular when
      using medium with succinate as the sole carbon source, a very pronounced and
      concentration-dependent decrease in the E. coli growth rate could be observed
      upon illumination in the presence of metal complex, which is attributed to the
      constrained energy metabolism under these conditions and a strong indicator of
      terminal oxidase inhibition by carbon monoxide delivered from the PhotoCORM. 

PMID- 24855639
TI  - Heavy metal accumulation in balsam pear and cowpea related to the geochemical
      factors of variable-charge soils in the Pearl River Delta, South China.
AB  - Variable-charge (v-c) soils in subtropical areas contain considerable amounts of
      iron/aluminum (Fe/Al) oxides that can strongly influence the fate of heavy metals
      in agricultural ecosystems. However, the relationship between heavy metal
      accumulation in vegetables and the geochemical factors associated with v-c soils
      in subtropical regions remains unknown. The present study investigated heavy
      metal accumulation under field conditions in the Pearl River Delta (PRD) by
      measuring the content of 8 heavy metals (zinc (Zn), arsenic (As), copper (Cu),
      mercury (Hg), lead (Pb), chromium (Cr), nickel (Ni) and cadmium (Cd)) in 43 pairs
      of v-c soil and vegetable (balsam pear and cowpea) samples. Soil physicochemical
      properties including pH, texture, organic matter and oxide minerals (Fe2O3, SiO2,
      Al2O3, CaO, MgO, K2O and Na2O) were also analyzed. Heavy metal accumulation from
      soil to vegetables was assessed based on bioconcentration factors (BCFs). The
      results showed that soil extractable Fe, oxide minerals and chemical weathering
      indices of v-c soils strongly affected heavy metal accumulation, whereas the
      content of Zn, Cu, Cr and Ni in vegetables was strongly affected by the soil clay
      content. Significant correlations were found between the BCFs of heavy metals and
      oxide minerals. However, no significant relationship was found between pH and
      heavy metal accumulation (except for Cu) in balsam pear and cowpea. Correlation
      analyses showed that a lower oxalate/DCB- extractable Fe content might indicate
      greater heavy metal (Zn, Cu, Hg, Cr and Ni) accumulation in vegetables.
      Therefore, it can be deduced that oxalate/DCB- extractable Fe content is a
      critical geochemical factor that determines the bioavailability of heavy metals
      and that iron biogeochemical cycles play vital roles in the fate of heavy metals
      in vegetable fields in this area. These findings provide new insights into the
      behaviors and fate of heavy metals in subtropical v-c soils and can be used to
      develop possible guidelines for vegetable safety management. 

PMID- 24855640
TI  - FABP3 protein promotes alpha-synuclein oligomerization associated with 1-methyl
      1,2,3,6-tetrahydropiridine-induced neurotoxicity.
AB  - alpha-Synuclein (alphaSyn) accumulation in dopaminergic (DA) neurons is partly
      regulated by long-chain polyunsaturated fatty acids. We found that fatty acid
      binding protein 3 (FABP3, H-FABP), a factor critical for arachidonic acid (AA)
      transport and metabolism in brain, is highly expressed in DA neurons. Fabp3 knock
      out (Fabp3(-/-)) mice were resistant to 1-methyl-1,2,3,6-tetrahydropiridine
      induced DA neurodegeneration in the substantia nigra pars compacta and showed
      improved motor function. Interestingly, FABP3 interacted with alphaSyn in the
      substantia nigra pars compacta, and alphaSyn accumulation following 1-methyl
      1,2,3,6-tetrahydropiridine treatment was attenuated in Fabp3(-/-) compared with
      wild-type mice. We confirmed that FABP3 overexpression aggravates AA-induced
      alphaSyn oligomerization and promotes cell death in PC12 cells, whereas
      overexpression of a mutant form of FABP3 lacking fatty-acid binding capacity did
      not. Taken together, alphaSyn oligomerization in DA neurons is likely aggravated
      by AA through FABP3 in Parkinson disease pathology. 

PMID- 24855641
TI  - Structural basis of G protein-coupled receptor-Gi protein interaction: formation
      of the cannabinoid CB2 receptor-Gi protein complex.
AB  - In this study, we applied a comprehensive G protein-coupled receptor-Galphai
      protein chemical cross-linking strategy to map the cannabinoid receptor subtype 2
      (CB2)-Galphai interface and then used molecular dynamics simulations to explore
      the dynamics of complex formation. Three cross-link sites were identified using
      LC-MS/MS and electrospray ionization-MS/MS as follows: 1) a sulfhydryl cross-link
      between C3.53(134) in TMH3 and the Galphai C-terminal i-3 residue Cys-351; 2) a
      lysine cross-link between K6.35(245) in TMH6 and the Galphai C-terminal i-5
      residue, Lys-349; and 3) a lysine cross-link between K5.64(215) in TMH5 and the
      Galphai alpha4beta6 loop residue, Lys-317. To investigate the dynamics and nature
      of the conformational changes involved in CB2.Gi complex formation, we carried
      out microsecond-time scale molecular dynamics simulations of the CB2
      R*.Galphai1beta1gamma2 complex embedded in a 1-palmitoyl-2-oleoyl
      phosphatidylcholine bilayer, using cross-linking information as validation. Our
      results show that although molecular dynamics simulations started with the G
      protein orientation in the beta2-AR*.Galphasbeta1gamma2 complex crystal
      structure, the Galphai1beta1gamma2 protein reoriented itself within 300 ns. Two
      major changes occurred as follows. 1) The Galphai1 alpha5 helix tilt changed due
      to the outward movement of TMH5 in CB2 R*. 2) A 25 degrees  clockwise rotation of
      Galphai1beta1gamma2 underneath CB2 R* occurred, with rotation ceasing when Pro
      139 (IC-2 loop) anchors in a hydrophobic pocket on Galphai1 (Val-34, Leu-194, Phe
      196, Phe-336, Thr-340, Ile-343, and Ile-344). In this complex, all three
      experimentally identified cross-links can occur. These findings should be
      relevant for other class A G protein-coupled receptors that couple to Gi
      proteins.

PMID- 24855642
TI  - Co-activation of nuclear factor-kappaB and myocardin/serum response factor
      conveys the hypertrophy signal of high insulin levels in cardiac myoblasts.
AB  - Hyperinsulinemia contributes to cardiac hypertrophy and heart failure in patients
      with the metabolic syndrome and type 2 diabetes. Here, high circulating levels of
      tumor necrosis factor (TNF)-alpha may synergize with insulin in signaling
      inflammation and cardiac hypertrophy. We tested whether high insulin affects
      activation of TNF-alpha-induced NF-kappaB and myocardin/serum response factor
      (SRF) to convey hypertrophy signaling in cardiac myoblasts. In canine cardiac
      myoblasts, treatment with high insulin (10(-8) to 10(-7) m) for 0-24 h increased
      insulin receptor substrate (IRS)-1 phosphorylation at Ser-307, decreased protein
      levels of chaperone-associated ubiquitin (Ub) E3 ligase C terminus of heat shock
      protein 70-interacting protein (CHIP), increased SRF activity, as well as beta
      myosin heavy chain (MHC) and myocardin expressions. Here siRNAs to myocardin or
      NF-kappaB, as well as CHIP overexpression prevented (while siRNA-mediated CHIP
      disruption potentiated) high insulin-induced SR element (SRE) activation and beta
      MHC expression. Insulin markedly potentiated TNF-alpha-induced NF-kappaB
      activation. Compared with insulin alone, insulin+TNF-alpha increased SRF/SRE
      binding and beta-MHC expression, which was reversed by the NF-kappaB inhibitor
      pyrrolidine dithiocarbamate (PDTC) and by NF-kappaB silencing. In the hearts of
      db/db diabetic mice, in which Akt phosphorylation was decreased, p38MAPK, Akt1,
      and IRS-1 phosphorylation at Ser-307 were increased, together with myocardin
      expression as well as SRE and NF-kappaB activities. In response to high insulin,
      cardiac myoblasts increase the expression or the promyogenic transcription
      factors myocardin/SRF in a CHIP-dependent manner. Insulin potentiates TNF-alpha
      in inducing NF-kappaB and SRF/SRE activities. In hyperinsulinemic states,
      myocardin may act as a nuclear effector of insulin, promoting cardiac
      hypertrophy. 

PMID- 24855643
TI  - YfgM is an ancillary subunit of the SecYEG translocon in Escherichia coli.
AB  - Protein secretion in Gram-negative bacteria is essential for both cell viability
      and pathogenesis. The vast majority of secreted proteins exit the cytoplasm
      through a transmembrane conduit called the Sec translocon in a process that is
      facilitated by ancillary modules, such as SecA, SecDF-YajC, YidC, and PpiD. In
      this study we have characterized YfgM, a protein with no annotated function. We
      found it to be a novel ancillary subunit of the Sec translocon as it co-purifies
      with both PpiD and the SecYEG translocon after immunoprecipitation and blue
      native/SDS-PAGE. Phenotypic analyses of strains lacking yfgM suggest that its
      physiological role in the cell overlaps with the periplasmic chaperones SurA and
      Skp. We, therefore, propose a role for YfgM in mediating the trafficking of
      proteins from the Sec translocon to the periplasmic chaperone network that
      contains SurA, Skp, DegP, PpiD, and FkpA. 

PMID- 24855644
TI  - Nitric oxide induces Ca2+-independent activity of the Ca2+/calmodulin-dependent
      protein kinase II (CaMKII).
AB  - Both signaling by nitric oxide (NO) and by the Ca(2+)/calmodulin (CaM)-dependent
      protein kinase II alpha isoform (CaMKIIalpha) are implicated in two opposing
      forms of synaptic plasticity underlying learning and memory, as well as in
      excitotoxic/ischemic neuronal cell death. For CaMKIIalpha, these functions
      specifically involve also Ca(2+)-independent autonomous activity, traditionally
      generated by Thr-286 autophosphorylation. Here, we demonstrate that NO-induced S
      nitrosylation of CaMKIIalpha also directly generated autonomous activity, and
      that CaMKII inhibition protected from NO-induced neuronal cell death. NO induced
      S-nitrosylation at Cys-280/289, and mutation of either site abolished autonomy,
      indicating that simultaneous nitrosylation at both sites was required.
      Additionally, autonomy was generated only when Ca(2+)/CaM was present during NO
      exposure. Thus, generation of this form of CaMKIIalpha autonomy requires
      simultaneous signaling by NO and Ca(2+). Nitrosylation also significantly reduced
      subsequent CaMKIIalpha autophosphorylation specifically at Thr-286, but not at
      Thr-305. A previously described reduction of CaMKII activity by S-nitrosylation
      at Cys-6 was also observed here, but only after prolonged (>5 min) exposure to NO
      donors. These results demonstrate a novel regulation of CaMKII by another second
      messenger system and indicate its involvement in excitotoxic neuronal cell death.

PMID- 24855645
TI  - Targeting spare CC chemokine receptor 5 (CCR5) as a principle to inhibit HIV-1
      entry.
AB  - CCR5 binds the chemokines CCL3, CCL4, and CCL5 and is the major coreceptor for
      HIV-1 entry into target cells. Chemokines are supposed to form a natural barrier
      against human immunodeficiency virus, type 1 (HIV-1) infection. However, we
      showed that their antiviral activity is limited by CCR5 adopting low-chemokine
      affinity conformations at the cell surface. Here, we investigated whether a pool
      of CCR5 that is not stabilized by chemokines could represent a target for
      inhibiting HIV infection. We exploited the characteristics of the chemokine
      analog PSC-RANTES (N-alpha-(n-nonanoyl)-des-Ser(1)-[l-thioprolyl(2), l
      cyclohexylglycyl(3)]-RANTES(4-68)), which displays potent anti-HIV-1 activity. We
      show that native chemokines fail to prevent high-affinity binding of PSC-RANTES,
      analog-mediated calcium release (in desensitization assays), and analog-mediated
      CCR5 internalization. These results indicate that a pool of spare CCR5 may bind
      PSC-RANTES but not native chemokines. Improved recognition of CCR5 by PSC-RANTES
      may explain why the analog promotes higher amounts of beta-arrestin 2.CCR5
      complexes, thereby increasing CCR5 down-regulation and HIV-1 inhibition.
      Together, these results highlight that spare CCR5, which might permit HIV-1 to
      escape from chemokines, should be targeted for efficient viral blockade. 

PMID- 24855646
TI  - The epigenetic drug 5-azacytidine interferes with cholesterol and lipid
      metabolism.
AB  - DNA methylation and histone acetylation inhibitors are widely used to study the
      role of epigenetic marks in the regulation of gene expression. In addition,
      several of these molecules are being tested in clinical trials or already in use
      in the clinic. Antimetabolites, such as the DNA-hypomethylating agent 5
      azacytidine (5-AzaC), have been shown to lower malignant progression to acute
      myeloid leukemia and to prolong survival in patients with myelodysplastic
      syndromes. Here we examined the effects of DNA methylation inhibitors on the
      expression of lipid biosynthetic and uptake genes. Our data demonstrate that,
      independently of DNA methylation, 5-AzaC selectively and very potently reduces
      expression of key genes involved in cholesterol and lipid metabolism (e.g. PCSK9,
      HMGCR, and FASN) in all tested cell lines and in vivo in mouse liver. Treatment
      with 5-AzaC disturbed subcellular cholesterol homeostasis, thereby impeding
      activation of sterol regulatory element-binding proteins (key regulators of lipid
      metabolism). Through inhibition of UMP synthase, 5-AzaC also strongly induced
      expression of 1-acylglycerol-3-phosphate O-acyltransferase 9 (AGPAT9) and
      promoted triacylglycerol synthesis and cytosolic lipid droplet formation.
      Remarkably, complete reversal was obtained by the co-addition of either UMP or
      cytidine. Therefore, this study provides the first evidence that inhibition of
      the de novo pyrimidine synthesis by 5-AzaC disturbs cholesterol and lipid
      homeostasis, probably through the glycerolipid biosynthesis pathway, which may
      contribute mechanistically to its beneficial cytostatic properties. 

PMID- 24855647
TI  - Regulated localization is sufficient for hormonal control of regulator of G
      protein signaling homology Rho guanine nucleotide exchange factors (RH-RhoGEFs).
AB  - The regulator of G protein signaling homology (RH) Rho guanine nucleotide
      exchange factors (RhoGEFs) (p115RhoGEF, leukemia-associated RhoGEF, and PDZ
      RhoGEF) contain an RH domain and are specific GEFs for the monomeric GTPase RhoA.
      The RH domains interact specifically with the alpha subunits of G12
      heterotrimeric GTPases. Activated Galpha13 modestly stimulates the exchange
      activity of both p115RhoGEF and leukemia-associated RhoGEF but not PDZ-RhoGEF.
      Because all three RH-RhoGEFs can localize to the plasma membrane upon expression
      of activated Galpha13, cellular localization of these RhoGEFs has been proposed
      as a mechanism for controlling their activity. We use a small molecule-regulated
      heterodimerization system to rapidly control the localization of RH-RhoGEFs.
      Acute localization of the proteins to the plasma membrane activates RhoA within
      minutes and to levels that are comparable with activation of RhoA by hormonal
      stimulation of G protein-coupled receptors. The catalytic activity of membrane
      localized RhoGEFs is not dependent on activated Galpha13. We further show that
      the conserved RH domains can rewire two different RacGEFs to activate Rac1 in
      response to a traditional activator of RhoA. Thus, RH domains act as independent
      detectors for activated Galpha13 and are sufficient to modulate the activity of
      RhoGEFs by hormones via mediating their localization to substrate, membrane
      associated RhoA. 

PMID- 24855648
TI  - Astrocyte elevated gene-1 is a novel modulator of HIV-1-associated
      neuroinflammation via regulation of nuclear factor-kappaB signaling and
      excitatory amino acid transporter-2 repression.
AB  - Astrocyte elevated gene-1 (AEG-1), a novel human immunodeficiency virus (HIV)-1
      and tumor necrosis factor (TNF)-alpha-inducible oncogene, has generated
      significant interest in the field of cancer research as a therapeutic target for
      many metastatic aggressive tumors. However, little is known about its role in
      astrocyte responses during HIV-1 central nervous system (CNS) infection and
      whether it contributes toward the development of HIV-associated neurocognitive
      disorders (HAND). Therefore, in this study, we investigated changes in AEG-1 CNS
      expression in HIV-1-infected brain tissues and elucidated a potential mechanism
      of AEG-1-mediated regulation of HAND. Immunoblotting and immunohistochemical
      analyses of HIV-1 seropositive and HIV-1 encephalitic human brain tissues
      revealed significantly elevated levels of AEG-1 protein. Immunohistochemical
      analyses of HIV-1 Tat transgenic mouse brain tissues also showed a marked
      increase in AEG-1 staining. Similar to in vivo observations, cultured astrocytes
      expressing HIV-1 Tat also revealed AEG-1 and cytokine up-regulation. Astrocytes
      treated with HAND-relevant stimuli, TNF-alpha, interleukin (IL)-1beta, and HIV-1,
      also significantly induced AEG-1 expression and nuclear translocation via
      activation of the nuclear factor (NF)-kappaB pathway. Co-immunoprecipitation
      studies demonstrated IL-1beta- or TNF-alpha-induced AEG-1 interaction with NF
      kappaB p65 subunit. AEG-1 knockdown decreased NF-kappaB activation, nuclear
      translocation, and transcriptional output in TNF-alpha-treated astrocytes.
      Moreover, IL-1beta treatment of AEG-1-overexpressing astrocytes significantly
      lowered expression of excitatory amino acid transporter 2, increased expression
      of excitatory amino acid transporter 2 repressor ying yang 1, and reduced
      glutamate clearance, a major transducer of excitotoxic neuronal damage. Findings
      from this study identify a novel transcriptional co-factor function of AEG-1 and
      further implicate AEG-1 in HAND-associated neuroinflammation. 

PMID- 24855649
TI  - Degradation of the deubiquitinating enzyme USP33 is mediated by p97 and the
      ubiquitin ligase HERC2.
AB  - Because the deubiquitinating enzyme USP33 is involved in several important
      cellular processes (beta-adrenergic receptor recycling, centrosome amplification,
      RalB signaling, and cancer cell migration), its levels must be carefully
      regulated. Using quantitative mass spectrometry, we found that the intracellular
      level of USP33 is highly sensitive to the activity of p97. Knockdown or chemical
      inhibition of p97 causes robust accumulation of USP33 due to inhibition of its
      degradation. The p97 adaptor complex involved in this function is the Ufd1-Npl4
      heterodimer. Furthermore, we identified HERC2, a HECT domain-containing E3
      ligase, as being responsible for polyubiquitination of USP33. Inhibition of p97
      causes accumulation of polyubiquitinated USP33, suggesting that p97 is required
      for postubiquitination processing. Thus, our study has identified several key
      molecules that control USP33 degradation within the ubiquitin-proteasome system. 

PMID- 24855650
TI  - Characterization of a Mycobacterium tuberculosis nanocompartment and its
      potential cargo proteins.
AB  - Mycobacterium tuberculosis has evolved various mechanisms by which the bacterium
      can maintain homeostasis under numerous environmental assaults generated by the
      host immune response. M. tuberculosis harbors enzymes involved in the oxidative
      stress response that aid in survival during the production of reactive oxygen
      species in activated macrophages. Previous studies have shown that a dye
      decolorizing peroxidase (DyP) is encapsulated by a bacterial nanocompartment,
      encapsulin (Enc), whereby packaged DyP interacts with Enc via a unique C-terminal
      extension. M. tuberculosis also harbors an encapsulin homolog (CFP-29, Mt-Enc),
      within an operon with M. tuberculosis DyP (Mt-DyP), which contains a C-terminal
      extension. Together these observations suggest that Mt-DyP interacts with Mt-Enc.
      Furthermore, it has been suggested that DyPs may function as either a heme
      dependent peroxidase or a deferrochelatase. Like Mt-DyP, M. tuberculosis iron
      storage ferritin protein, Mt-BfrB, and an M. tuberculosis protein involved in
      folate biosynthesis, 7,8-dihydroneopterin aldolase (Mt-FolB), have C-terminal
      tails that could also interact with Mt-Enc. For the first time, we show by co
      purification and electron microscopy that mycobacteria via Mt-Enc can encapsulate
      Mt-DyP, Mt-BfrB, and Mt-FolB. Functional studies of free or encapsulated proteins
      demonstrate that they retain their enzymatic activity within the Mt-Enc
      nanocompartment. Mt-DyP, Mt-FolB, and Mt-BfrB all have antioxidant properties,
      suggesting that if these proteins are encapsulated by Mt-Enc, then this nanocage
      may play a role in the M. tuberculosis oxidative stress response. This report
      provides initial structural and biochemical clues regarding the molecular
      mechanisms that utilize compartmentalization by which the mycobacterial cell may
      aid in detoxification of the local environment to ensure long term survival. 

PMID- 24855651
TI  - Novel zinc-binding site in the E2 domain regulates amyloid precursor-like protein
      1 (APLP1) oligomerization.
AB  - The amyloid precursor protein (APP) and the APP-like proteins 1 and 2 (APLP1 and
      APLP2) are a family of multidomain transmembrane proteins possessing homo- and
      heterotypic contact sites in their ectodomains. We previously reported that
      divalent metal ions dictate the conformation of the extracellular APP E2 domain
      (Dahms, S. O., Konnig, I., Roeser, D., Guhrs, K.-H., Mayer, M. C., Kaden, D.,
      Multhaup, G., and Than, M. E. (2012) J. Mol. Biol. 416, 438-452), but unresolved
      is the nature and functional importance of metal ion binding to APLP1 and APLP2.
      We found here that zinc ions bound to APP and APLP1 E2 domains and mediated their
      oligomerization, whereas the APLP2 E2 domain interacted more weakly with zinc
      possessing a less surface-exposed zinc-binding site, and stayed monomeric. Copper
      ions bound to E2 domains of all three proteins. Fluorescence resonance energy
      transfer (FRET) analyses examined the effect of metal ion binding to APP and
      APLPs in the cellular context in real time. Zinc ions specifically induced APP
      and APLP1 oligomerization and forced APLP1 into multimeric clusters at the plasma
      membrane consistent with zinc concentrations in the blood and brain. The observed
      effects were mediated by a novel zinc-binding site within the APLP1 E2 domain as
      APLP1 deletion mutants revealed. Based upon its cellular localization and its
      dominant response to zinc ions, APLP1 is mainly affected by extracellular zinc
      among the APP family proteins. We conclude that zinc binding and APP/APLP
      oligomerization are intimately linked, and we propose that this represents a
      novel mechanism for regulating APP/APLP protein function at the molecular level. 

PMID- 24855652
TI  - Novel isoforms of heat shock transcription factor 1, HSF1gammaalpha and
      HSF1gammabeta, regulate chaperone protein gene transcription.
AB  - The heat shock response, resulting in the production of heat shock proteins or
      molecular chaperones, is triggered by elevated temperature and a variety of other
      stressors. Its master regulator is heat shock transcription factor 1 (HSF1). Heat
      shock factors generally exist in multiple isoforms. The two known isoforms of
      HSF1 differ in the inclusion (HSF1alpha) or exclusion (HSF1beta) of exon 11.
      Although there are some data concerning the differential expression patterns and
      transcriptional activities of HSF2 isoforms during development, little is known
      about the distinct properties of the HSF1 isoforms. Here we present evidence for
      two novel HSF1 isoforms termed HSF1gammaalpha and HSF1gammabeta, and we show that
      the HSF1 isoform ratio differentially regulates heat shock protein gene
      transcription. Hsf1gamma isoforms are expressed in various mouse tissues and are
      translated into protein. Furthermore, after heat shock, HSF1gamma isoforms are
      exported from the nucleus more rapidly or degraded more quickly than HSF1alpha or
      HSF1beta. We also show that each individual HSF1 isoform is sufficient to induce
      the heat shock response and that expression of combinations of HSF1 isoforms, in
      particular HSF1alpha and HSF1beta, results in a synergistic enhancement of the
      transcriptional response. In addition, HSF1gamma isoforms potentially suppress
      the synergistic effect of HSF1alpha and HSF1beta co-expression. Collectively, our
      observations suggest that the expression of HSF1 isoforms in a specific ratio
      provides an additional layer in the regulation of heat shock protein gene
      transcription. 

PMID- 24855655
TI  - Alpha linolenic acid (ALA) from Rosa canina, sacha inchi and chia oils may
      increase ALA accretion and its conversion into n-3 LCPUFA in diverse tissues of
      the rat.
AB  - Alpha-linolenic acid (ALA) is an essential n-3 PUFA; its n-3 LCPUFA derivatives
      EPA and DHA, which have diverse beneficial effects, are scarce in the human diet.
      In recent years nontraditional vegetable oils rich in ALA (up to 45%) have been
      developed as new alternatives to increase ALA consumption. This work evaluated
      the accretion of ALA, EPA and DHA into the phospholipids extracted from
      erythrocytes, liver, kidney, small intestine, heart, quadriceps and the brain in
      rats fed sunflower (SFO), canola (CO), Rosa canina (RCO), sacha inchi (Plukenetia
      volubilis, SIO) and chia (Salvia hispanica, ChO) oils. Five experimental groups
      (n = 12 per group) were fed for 21 days with SFO (1% ALA), CO (10% ALA), RCO (33%
      ALA), SIO (49% ALA), and ChO (64% ALA). SIO and ChO allowed higher ALA accretion
      in all tissues, except the brain, and a reduction in the content of arachidonic
      acid in all tissues except the brain. EPA was increased in erythrocytes, liver,
      kidney, small intestine, heart and quadriceps, but not in the brain. DHA was
      increased in the liver, small intestine and brain tissues. Our results
      demonstrate that ALA, when provided in significant amounts, can be converted into
      n-3 LCPUFA, mostly DHA in the liver and brain. It is suggested that oils rich in
      ALA, such as SIO and ChO, are good sources for obtaining higher tissue levels of
      ALA, also allowing its selective conversion into n-3 LCPUFA in some tissues of
      the rat. 

PMID- 24855654
TI  - Comparative evaluation of the metabolic effects of hydroxytyrosol and its
      lipophilic derivatives (hydroxytyrosyl acetate and ethyl hydroxytyrosyl ether) in
      hypercholesterolemic rats.
AB  - Hydroxytyrosol (HT), a virgin olive oil phenolic phytochemical with proven health
      benefits, has been used to generate new lipophilic antioxidants to preserve fats
      and oils against autoxidation. The aim of this work is to comparatively evaluate
      the physiological effects of HT and its lipophilic derivatives, hydroxytyrosyl
      acetate (HT-Ac) and ethyl hydroxytyrosyl ether (HT-Et), in high-cholesterol fed
      animals. Male Wistar rats (n = 8) were fed a standard diet (C group), a
      cholesterol-rich diet (Chol group) or a cholesterol-rich diet supplemented with
      phenolic compounds (HT group, HT-Ac group and HT-Et group) for 8 weeks. Body and
      tissue weights, the lipid profile, redox status, and biochemical, hormonal, and
      inflammatory biomarkers were evaluated. Plasma levels of total cholesterol, LDL
      cholesterol, glucose, insulin and leptin, as well as malondialdehyde in serum
      increased in Chol compared to C (p < 0.05). Rats fed the test diets had improved
      glucose, insulin, leptin and MDA levels and antioxidant capacity status, with HT
      Ac being the most effective compound. The studied phenolic compounds also
      modulated TNF-alpha and IL-1beta plasma levels compared to Chol. HT-Ac and HT-Et
      improved adipose tissue distribution and adipokine production, decreasing MCP-1
      and IL-1beta levels. Our results confirm the metabolic effects of HT, which are
      maintained and even improved by hydrophobic derivatives, particularly HT-Ac. 

PMID- 24855656
TI  - A microfluidic platform for profiling biomechanical properties of bacteria.
AB  - The ability to resist mechanical forces is necessary for the survival and
      division of bacteria and has traditionally been probed using specialized, low
      throughput techniques such as atomic force microscopy and optical tweezers. Here
      we demonstrate a microfluidic technique to profile the stiffness of individual
      bacteria and populations of bacteria. The approach is similar to micropipette
      aspiration used to characterize the biomechanical performance of eukaryotic
      cells. However, the small size and greater stiffness of bacteria relative to
      eukaryotic cells prevents the use of micropipettes. Here we present devices with
      sub-micron features capable of applying loads to bacteria in a controlled
      fashion. Inside the device, individual bacteria are flowed and trapped in tapered
      channels. Less stiff bacteria undergo greater deformation and therefore travel
      further into the tapered channel. Hence, the distance traversed by bacteria into
      a tapered channel is inversely related to cell stiffness. We demonstrate the
      ability of the device to characterize hundreds of bacteria at a time, measuring
      stiffness at 12 different applied loads at a time. The device is shown to
      differentiate between two bacterial species, E. coli (less stiff) and B. subtilis
      (more stiff), and detect differences between E. coli submitted to antibiotic
      treatment from untreated cells of the same species/strain. The microfluidic
      device is advantageous in that it requires only minimal sample preparation, no
      permanent cell immobilization, no staining/labeling and maintains cell viability.
      Our device adds detection of biomechanical phenotypes of bacteria to the list of
      other bacterial phenotypes currently detectable using microchip-based methods and
      suggests the feasibility of separating/selecting bacteria based on differences in
      cell stiffness. 

PMID- 24855657
TI  - A fluorescent switch for sequentially and selectively sensing copper(II) and L
      histidine in vitro and in living cells.
AB  - Herein, we report the development of a new fluorescent switch for sequential and
      selective sensing of Cu(2+) and L-histidine (L-His) in vitro and in living cells
      for the first time. In the absence of metal ions, Ac-SAACQ-Gly-Gly-Gly-Lys (FITC)
      (1) exhibits comparable fluorescence to that of free FITC. In the presence of
      metal ions, 1 selectively coordinates to Cu(2+) , causing its fluorescence
      emission to be quenched via photoinduced electron transfer. Interestingly, the as
      formed 1-Cu(2+) complex selectively responds to L-His among the 20 natural amino
      acids by turning its fluorescence on. This property of fluorescence switch of 1
      was successfully applied for qualitatively and quantitatively sensing Cu(2+) and
      L-His in vitro. Using this dual functional probe, we also sequentially imaged
      Cu(2+) and L-His in living HepG2 cells. Our new probe 1 could be applied for not
      only environmental monitoring but also biomolecule detection in the near future.

PMID- 24855653
TI  - Proposed carrier lipid-binding site of undecaprenyl pyrophosphate phosphatase
      from Escherichia coli.
AB  - Undecaprenyl pyrophosphate phosphatase (UppP), an integral membrane protein,
      catalyzes the dephosphorylation of undecaprenyl pyrophosphate to undecaprenyl
      phosphate, which is an essential carrier lipid in the bacterial cell wall
      synthesis. Sequence alignment reveals two consensus regions, containing glutamate
      rich (E/Q)XXXE plus PGXSRSXXT motifs and a histidine residue, specific to the
      bacterial UppP enzymes. The predicted topological model suggests that both of
      these regions are localized near the aqueous interface of UppP and face the
      periplasm, implicating that its enzymatic function is on the outer side of the
      plasma membrane. The mutagenesis analysis demonstrates that most of the mutations
      (E17A/E21A, H30A, S173A, R174A, and T178A) within the consensus regions are
      completely inactive, indicating that the catalytic site of UppP is constituted by
      these two regions. Enzymatic analysis also shows an absolute requirement of
      magnesium or calcium ions in enzyme activity. The three-dimensional structural
      model and molecular dynamics simulation studies have shown a plausible structure
      of the catalytic site of UppP and thus provides insights into the molecular basis
      of the enzyme-substrate interaction in membrane bilayers. 

PMID- 24855659
TI  - Editorial--probe and chip approaches to cell analysis.

PMID- 24855658
TI  - Micropatterning neuronal networks.
AB  - Spatially organised neuronal networks have wide reaching applications, including
      fundamental research, toxicology testing, pharmaceutical screening and the
      realisation of neuronal implant interfaces. Despite the large number of methods
      catalogued in the literature there remains the need to identify a method that
      delivers high pattern compliance, long-term stability and is widely accessible to
      neuroscientists. In this comparative study, aminated (polylysine/polyornithine
      and aminosilanes) and cytophobic (poly(ethylene glycol) (PEG) and methylated)
      material contrasts were evaluated. Backfilling plasma stencilled PEGylated
      substrates with polylysine does not produce good material contrasts, whereas
      polylysine patterned on methylated substrates becomes mobilised by agents in the
      cell culture media which results in rapid pattern decay. Aminosilanes, polylysine
      substitutes, are prone to hydrolysis and the chemistries prove challenging to
      master. Instead, the stable coupling between polylysine and PLL-g-PEG can be
      exploited: Microcontact printing polylysine onto a PLL-g-PEG coated glass
      substrate provides a simple means to produce microstructured networks of primary
      neurons that have superior pattern compliance during long term (>1 month)
      culture. 

PMID- 24855661
TI  - Photo quiz: A 50-year-old with a 2-day history of right upper quadrant tenderness
      and septicemia caused by a Gram-negative organism.

PMID- 24855660
TI  - Requirement for pectin methyl esterase and preference for fragmented over native
      pectins for wall-associated kinase-activated, EDS1/PAD4-dependent stress response
      in Arabidopsis.
AB  - The wall-associated kinases (WAKs) have a cytoplasmic protein kinase domain that
      spans the plasma membrane and binds pectin in the extracellular matrix of plants.
      WAKs are required for cell expansion during Arabidopsis seedling development but
      are also an integral part of the response to pathogens and stress that present
      oligogalacturonides (OGs), which subsequently bind to WAKs and activate a MPK6
      (mitogen-activated protein kinase)-dependent pathway. It was unclear how WAKs
      distinguish native pectin polymers and OGs to activate one or the other of these
      two pathways. A dominant allele of WAK2 constitutively activates the stress
      response, and we show here that the effect is dependent upon EDS1 and PAD4,
      transcriptional activators involved in the pathogen response. Moreover, the WAK2
      dominant allele is suppressed by a null allele of a pectin methyl esterase (PME3)
      whose activity normally leads to cross-linking of pectins in the cell wall.
      Although OGs activate a transcriptional response in wild type, the response is
      enhanced in a pme3/pme3 null, consistent with a competition by OG and native
      polymers for activation of WAKs. This provides a plausible mechanism for WAKs to
      distinguish an expansion from a stress pathway. 

PMID- 24855662
TI  - Diagnostic value of a PCR-based technique for prosthetic joint infection.

PMID- 24855663
TI  - Reply to "Diagnostic value of a PCR-based technique for prosthetic joint
      infection".

PMID- 24855669
TI  - Avian-style respiration allowed gigantism in pterosaurs.
AB  - Powered flight has evolved three times in the vertebrates: in the birds, the bats
      and the extinct pterosaurs. The largest bats ever known are at least an order of
      magnitude smaller than the largest members of the other two groups. Recently, it
      was argued that different scaling of wingbeat frequencies to body mass in birds
      and bats can help explain why the largest birds are larger than the largest bats.
      Here, I extend this argument in two ways. Firstly, I suggest that different
      respiratory physiologies are key to understanding the restriction on bat maximum
      size compared with birds. Secondly, I argue that a respiratory physiology similar
      to birds would have been a prerequisite for the gigantism seen in pterosaurs. 

PMID- 24855668
TI  - The hydrodynamics of swimming at intermediate Reynolds numbers in the water
      boatman (Corixidae).
AB  - The fluid forces that govern propulsion determine the speed and energetic cost of
      swimming. These hydrodynamics are scale dependent and it is unclear what forces
      matter to the tremendous diversity of aquatic animals that are between a
      millimeter and a centimeter in length. Animals at this scale generally operate
      within the regime of intermediate Reynolds numbers, where both viscous and
      inertial fluid forces have the potential to play a role in propulsion. The
      present study aimed to resolve which forces create thrust and drag in the
      paddling of the water boatman (Corixidae), an animal that spans much of the
      intermediate regime (10<Re<200). By measuring the force generated by tethered
      water boatmen, we found that thrust is generated primarily by drag on the
      paddling appendages, with a negligible contribution from the acceleration
      reaction force. Based on these findings, we developed a forward-dynamic model of
      propulsion in free swimming that accurately predicted changes in the body's
      center of mass over time. For both tethered and free swimming, we used non-linear
      optimization algorithms to determine the force coefficients that best matched our
      measurements. With this approach, the drag coefficients on the body and paddle
      were found to be up to three times greater than on static structures in fully
      developed flow at the same Reynolds numbers. This is likely a partial consequence
      of unsteady interactions between the paddles or between the paddles and the body.
      In addition, the maximum values for these coefficients were inversely related to
      the Reynolds number, which suggests that viscous forces additionally play an
      important role in the hydrodynamics of small water boatmen. This understanding
      for the major forces that operate at intermediate Reynolds numbers offers a basis
      for interpreting the mechanics, energetics and functional morphology of swimming
      in many small aquatic animals.

PMID- 24855670
TI  - Transition from wing to leg forces during landing in birds.
AB  - Transitions to and from the air are critical for aerial locomotion and likely
      shaped the evolution of flying animals. Research on take-off demonstrates that
      legs generate greater body accelerations compared with wings, and thereby
      contribute more to initial flight velocity. Here, we explored coordination
      between wings and legs in two species with different wingbeat styles, and
      quantified force production of these modules during the final phase of landing.
      We used the same birds that we had previously studied during take-off: zebra
      finch (Taeniopygia guttata, N=4) and diamond dove (Geopelia cuneata, N=3). We
      measured kinematics using high-speed video, aerodynamics using particle image
      velocimetry, and ground-reaction forces using a perch mounted on a force plate.
      In contrast with the first three wingbeats of take-off, the final four wingbeats
      during landing featured ~2 times greater force production. Thus, wings contribute
      proportionally more to changes in velocity during the last phase of landing
      compared with the initial phase of take-off. The two species touched down at the
      same velocity (~1 m s(-1)), but they exhibited significant differences in the
      timing of their final wingbeat relative to touchdown. The ratio of average wing
      force to peak leg force was greater in diamond doves than in zebra finches. Peak
      ground reaction forces during landing were ~50% of those during take-off,
      consistent with the birds being motivated to control landing. Likewise,
      estimations of mechanical energy flux for both species indicate that wings
      produce 3-10 times more mechanical work within the final wingbeats of flight
      compared with the kinetic energy of the body absorbed by legs during ground
      contact.

PMID- 24855671
TI  - Ambient noise causes independent changes in distinct spectro-temporal features of
      echolocation calls in horseshoe bats.
AB  - One of the most efficient mechanisms to optimize signal-to-noise ratios is the
      Lombard effect - an involuntary rise in call amplitude due to ambient noise. It
      is often accompanied by changes in the spectro-temporal composition of calls. We
      examined the effects of broadband-filtered noise on the spectro-temporal
      composition of horseshoe bat echolocation calls, which consist of a constant
      frequency component and initial and terminal frequency-modulated components. We
      found that the frequency-modulated components became larger for almost all noise
      conditions, whereas the bandwidth of the constant-frequency component increased
      only when broadband-filtered noise was centered on or above the calls' dominant
      or fundamental frequency. This indicates that ambient noise independently
      modifies the associated acoustic parameters of the Lombard effect, such as
      spectro-temporal features, and could significantly affect the bat's ability to
      detect and locate targets. Our findings may be of significance in evaluating the
      impact of environmental noise on echolocation behavior in bats.

PMID- 24855672
TI  - The mechanics and behavior of cliff swallows during tandem flights.
AB  - Cliff swallows (Petrochelidon pyrrhonota) are highly maneuverable social birds
      that often forage and fly in large open spaces. Here we used multi-camera
      videography to measure the three-dimensional kinematics of their natural flight
      maneuvers in the field. Specifically, we collected data on tandem flights,
      defined as two birds maneuvering together. These data permit us to evaluate
      several hypotheses on the high-speed maneuvering flight performance of birds. We
      found that high-speed turns are roll-based, but that the magnitude of the
      centripetal force created in typical maneuvers varied only slightly with flight
      speed, typically reaching a peak of ~2 body weights. Turning maneuvers typically
      involved active flapping rather than gliding. In tandem flights the following
      bird copied the flight path and wingbeat frequency (~12.3 Hz) of the lead bird
      while maintaining position slightly above the leader. The lead bird turned in a
      direction away from the lateral position of the following bird 65% of the time on
      average. Tandem flights vary widely in instantaneous speed (1.0 to 15.6 m s(-1))
      and duration (0.72 to 4.71 s), and no single tracking strategy appeared to
      explain the course taken by the following bird.

PMID- 24855674
TI  - Conditioned hearing sensitivity reduction in a bottlenose dolphin (Tursiops
      truncatus).
AB  - The conditioned change in hearing sensitivity during a warning sound preceding a
      loud sound was investigated in the bottlenose dolphin. Hearing sensitivity was
      measured using pip-train test stimuli and auditory evoked potential recording.
      When the test/warning stimulus with a frequency of 22.5 or 32 kHz preceded the
      loud sound with a frequency of 22.5 kHz and a sound pressure level of 165 dB re.
      1 MUPa rms, hearing thresholds before the loud sound increased relative to the
      baseline. The threshold increased up to 15 dB. In order to further investigate
      whether the observed threshold increase was due to conditioning, the dependence
      of the effect on warning duration and inter-trial interval was investigated. The
      duration of the warning substantially influenced the effect. Shorter warnings
      resulted in deeper suppression of responses and higher threshold increases than
      longer warnings. In contrast, the effect was nearly independent of the duration
      of the inter-trial interval, i.e. it was independent of the delay from the loud
      sound to the test/warning sound in the subsequent trial. These data are
      considered as evidence that the observed hearing threshold increases were not a
      result of the unconditioned effect of the loud sound and were instead a
      manifestation of a conditioned dampening of hearing when the bottlenose dolphin
      anticipated the quick appearance of a loud sound in the same way as previously
      demonstrated in the false killer whale.

PMID- 24855675
TI  - Long-axis rotation: a missing degree of freedom in avian bipedal locomotion.
AB  - Ground-dwelling birds are typically characterized as erect bipeds having hind
      limbs that operate parasagittally. Consequently, most previous research has
      emphasized flexion/extension angles and moments as calculated from a lateral
      perspective. Three-dimensional (3D) motion analyses have documented non-planar
      limb movements, but the skeletal kinematics underlying changes in foot
      orientation and transverse position remain unclear. In particular, long-axis
      rotation of the proximal limb segments is extremely difficult to measure with
      topical markers. Here, we present six degree of freedom skeletal kinematic data
      from maneuvering guineafowl acquired by marker-based XROMM (X-ray Reconstruction
      of Moving Morphology). Translations and rotations of the hips, knees, ankles and
      pelvis were derived from animated bone models using explicit joint coordinate
      systems. We distinguished sidesteps, sidestep yaws, crossover yaws, sidestep
      turns and crossover turns, but birds often performed a sequence of blended
      partial maneuvers. Long-axis rotation of the femur (up to 38 deg) modulated the
      foot's transverse position. Long-axis rotation of the tibiotarsus (up to 65 deg)
      also affected medio-lateral positioning, but primarily served to either re-orient
      a swing phase foot or yaw the body about a stance phase foot. Tarsometatarsal
      long-axis rotation was minimal, as was hip, knee and ankle abduction/adduction.
      Despite having superficially hinge-like joints, birds coordinate substantial long
      axis rotations of the hips and knees to execute complex 3D maneuvers while
      striking a diversity of non-planar poses.

PMID- 24855673
TI  - Social status differences regulate the serotonergic system of a cichlid fish,
      Astatotilapia burtoni.
AB  - Serotonin (5-HT) inhibits aggression and modulates aspects of sexual behaviour in
      many species, but the mechanisms responsible are not well understood. Here, we
      exploited the social dominance hierarchy of Astatotilapia burtoni to understand
      the role of the serotonergic system in long-term maintenance of social status. We
      identified three populations of 5-HT cells in dorsal and ventral periventricular
      pretectal nuclei (PPd, PPv), the nucleus of the paraventricular organ (PVO) and
      raphe. Dominant males had more 5-HT cells than subordinates in the raphe, but the
      size of these cells did not differ between social groups. Subordinates had higher
      serotonergic turnover in the raphe and preoptic area (POA), a nucleus essential
      for hypothalamic-pituitary-gonadal (HPG) axis function. The relative abundance of
      mRNAs for 5-HT receptor (5-HTR) subtypes 1A and 2A (htr1a, htr2a) was higher in
      subordinates, a difference restricted to the telencephalon. Because social status
      is tightly linked to reproductive capacity, we asked whether serotonin turnover
      and the expression of its receptors correlated with testes size and circulating
      levels of 11-ketotestosterone (11-KT). We found negative correlations between
      both raphe and POA serotonin turnover and testes size, as well as between htr1a
      mRNA levels and circulating 11-KT. Thus, increased serotonin turnover in non
      aggressive males is restricted to specific brain nuclei and is associated with
      increased expression of 5-HTR subtypes 1A and 2A exclusively in the
      telencephalon.

PMID- 24855676
TI  - Metabolic suppression during protracted exposure to hypoxia in the jumbo squid,
      Dosidicus gigas, living in an oxygen minimum zone.
AB  - The jumbo squid, Dosidicus gigas, can survive extended forays into the oxygen
      minimum zone (OMZ) of the Eastern Pacific Ocean. Previous studies have
      demonstrated reduced oxygen consumption and a limited anaerobic contribution to
      ATP production, suggesting the capacity for substantial metabolic suppression
      during hypoxic exposure. Here, we provide a more complete description of energy
      metabolism and explore the expression of proteins indicative of transcriptional
      and translational arrest that may contribute to metabolic suppression. We
      demonstrate a suppression of total ATP demand under hypoxic conditions (1%
      oxygen, PO2 =0.8 kPa) in both juveniles (52%) and adults (35%) of the jumbo
      squid. Oxygen consumption rates are reduced to 20% under hypoxia relative to air
      saturated controls. Concentrations of arginine phosphate (Arg-P) and ATP declined
      initially, reaching a new steady state (~30% of controls) after the first hour of
      hypoxic exposure. Octopine began accumulating after the first hour of hypoxic
      exposure, once Arg-P breakdown resulted in sufficient free arginine for
      substrate. Octopine reached levels near 30 mmol g(-1) after 3.4 h of hypoxic
      exposure. Succinate did increase through hypoxia but contributed minimally to
      total ATP production. Glycogenolysis in mantle muscle presumably serves to
      maintain muscle functionality and balance energetics during hypoxia. We provide
      evidence that post-translational modifications on histone proteins and
      translation factors serve as a primary means of energy conservation and that
      select components of the stress response are altered in hypoxic squids. Reduced
      ATP consumption under hypoxia serves to maintain ATP levels, prolong fuel store
      use and minimize the accumulation of acidic intermediates of anaerobic ATP
      generating pathways during prolonged diel forays into the OMZ. Metabolic
      suppression likely limits active, daytime foraging at depth in the core of the
      OMZ, but confers an energetic advantage over competitors that must remain in
      warm, oxygenated surface waters. Moreover, the capacity for metabolic suppression
      provides habitat flexibility as OMZs expand as a result of climate change.

PMID- 24855677
TI  - Parental experience of a risky environment leads to improved offspring growth
      rate.
AB  - Parasites (or diseases) are a major selective force for the evolution of life
      history traits and parasite-host evolution. Mothers can show a variety of
      responses to parasites during pregnancy, with different consequences for them or
      their offspring. However, whether information in the maternal environment before
      pregnancy can cause a change in the phenotype of the offspring is unknown. To
      avoid the confounding effect of pathogens and to reduce the risk of a direct
      effect of maternal immune system activation, we injected female laboratory mice
      with lipopolysaccharides (LPS) before they mated. In order to provide constant
      information on the potential infectious risk of the environment, females were
      mated with males that were also exposed to LPS before mating. Offspring from
      immune-challenged parents were larger and grew at a faster rate than offspring
      from control parents (injected with PBS). Additionally, offspring from immune
      challenged parents that suffered the most from inflammation grew at a faster rate
      than offspring from low suffering parents. Producing heavier offspring that will
      reach sexual maturity earlier is likely to have fitness benefits for parents and
      offspring through improved reproductive success.

PMID- 24855678
TI  - Bees associate colour cues with differences in pollen rewards.
AB  - In contrast to the wealth of knowledge concerning sucrose-rewarded learning, the
      question of whether bees learn when they collect pollen from flowers has been
      little addressed. The nutritional value of pollen varies considerably between
      species, and it may be that bees learn the features of flowers that produce
      pollen best suited to the dietary requirements of their larvae. It is still
      unknown, however, whether a non-ingestive reward pathway for pollen learning
      exists, and how foraging bees sense differences between pollen types. Here we
      adopt a novel experimental approach testing the learning ability of bees with
      pollen rewards. Bumblebees were reared under controlled laboratory conditions. To
      establish which pollen rewards are distinguishable, individual bees were given
      the choice of collecting two types of pollen, diluted to varying degrees with
      indigestible alpha-cellulose. Bees preferentially collected a particular pollen
      type, but this was not always the most concentrated sample. Preferences were
      influenced by the degree of similarity between samples and also by the period of
      exposure, with bees more readily collecting samples of lower pollen concentration
      after five trials. When trained differentially, bees were able to associate an
      initially less-preferred contextual colour with the more concentrated sample,
      whilst their pollen preferences did not change. Successful learning of contextual
      cues seems to maintain pollen foraging preferences over repeated exposures,
      suggesting that fast learning of floral cues may preclude continuous sampling and
      evaluation of alternative reward sources, leading to constancy in pollen
      foraging. 

PMID- 24855679
TI  - Ontogenetic investigation of underwater hearing capabilities in loggerhead sea
      turtles (Caretta caretta) using a dual testing approach.
AB  - Sea turtles reside in different acoustic environments with each life history
      stage and may have different hearing capacity throughout ontogeny. For this
      study, two independent yet complementary techniques for hearing assessment, i.e.
      behavioral and electrophysiological audiometry, were employed to (1) measure
      hearing in post-hatchling and juvenile loggerhead sea turtles Caretta caretta (19
      62 cm straight carapace length) to determine whether these migratory turtles
      exhibit an ontogenetic shift in underwater auditory detection and (2) evaluate
      whether hearing frequency range and threshold sensitivity are consistent in
      behavioral and electrophysiological tests. Behavioral trials first required
      training turtles to respond to known frequencies, a multi-stage, time-intensive
      process, and then recording their behavior when they were presented with sound
      stimuli from an underwater speaker using a two-response forced-choice paradigm.
      Electrophysiological experiments involved submerging restrained, fully conscious
      turtles just below the air-water interface and recording auditory evoked
      potentials (AEPs) when sound stimuli were presented using an underwater speaker.
      No significant differences in behavior-derived auditory thresholds or AEP-derived
      auditory thresholds were detected between post-hatchling and juvenile sea
      turtles. While hearing frequency range (50-1000/1100 Hz) and highest sensitivity
      (100-400 Hz) were consistent in audiograms pooled by size class for both behavior
      and AEP experiments, both post-hatchlings and juveniles had significantly higher
      AEP-derived than behavior-derived auditory thresholds, indicating that behavioral
      assessment is a more sensitive testing approach. The results from this study
      suggest that post-hatchling and juvenile loggerhead sea turtles are low-frequency
      specialists, exhibiting little differences in threshold sensitivity and frequency
      bandwidth despite residence in acoustically distinct environments throughout
      ontogeny.

PMID- 24855681
TI  - Rh versus pH: the role of Rhesus glycoproteins in renal ammonia excretion during
      metabolic acidosis in a freshwater teleost fish.
AB  - Increased renal ammonia excretion in response to metabolic acidosis is thought to
      be a conserved response in vertebrates. We tested the hypothesis that Rhesus (Rh)
      glycoproteins in the kidney of the freshwater common carp, Cyprinus carpio, play
      a crucial role in regulating renal ammonia excretion during chronic metabolic
      acidosis. Exposure to water pH 4.0 (72 h) resulted in a classic metabolic
      acidosis with reduced plasma arterial pH and [HCO3(-)], no change in PCO2 and
      large changes in renal function. Urine [NH4(+)] as well as [titratable acidity
      HCO3(-)] rose significantly over the acid exposure, but the profound reduction
      (fivefold) in urine flow rates eliminated the expected elevations in renal
      ammonia excretion. Low urine flow rates may be a primary strategy to conserve
      ions, as urinary excretion rates of Na(+), Cl(-) and Ca(2+) were significantly
      lower during the acid exposure relative to the control period. Interestingly,
      renal Rhcg1 mRNA and protein levels were elevated in acid-exposed relative to
      control groups, along with mRNA levels of several ion transporters, including the
      Na(+)/H(+) exchanger, H(+)-ATPase and Na(+)/K(+)-ATPase. Immunofluorescence
      microscopy showed a strong apical Rhcg1 signal in distal tubules. Taken together,
      these data show that renal Rh glycoproteins and associated ion transporters are
      responsive to metabolic acidosis, but conservation of ions through reduced urine
      flow rates takes primacy over renal acid-base regulation in the freshwater C.
      carpio. We propose that an 'acid/base-ion balance' compromise explains the
      variable renal responses to metabolic acidosis in freshwater teleosts.

PMID- 24855680
TI  - Role of oleoylethanolamide as a feeding regulator in goldfish.
AB  - Oleoylethanolamide (OEA) is a bioactive lipid mediator, produced in the intestine
      and other tissues, which is involved in energy balance regulation in mammals,
      modulating feeding and lipid metabolism. The purpose of the present study was to
      investigate the presence and possible role of OEA in feeding regulation in
      goldfish (Carassius auratus). We assessed whether goldfish peripheral tissues and
      brain contain OEA and their regulation by nutritional status. OEA was detected in
      all studied tissues (liver, intestinal bulb, proximal intestine, muscle,
      hypothalamus, telencephalon and brainstem). Food deprivation (48 h) reduced
      intestinal OEA levels and levels increased upon re-feeding, suggesting that this
      compound may be involved in the short-term regulation of food intake in goldfish,
      as a satiety factor. Next, the effects of acute intraperitoneal administration of
      OEA on feeding, swimming and plasma levels of glucose and triglycerides were
      analysed. Food intake, swimming activity and circulating triglyceride levels were
      reduced by OEA 2 h post-injection. Finally, the possible interplay among OEA and
      other feeding regulators (leptin, cholecystokinin, ghrelin, neuropeptide Y,
      orexin and monoamines) was investigated. OEA actions on energy homeostasis in
      goldfish could be mediated, at least in part, through interactions with ghrelin
      and the serotonergic system, as OEA treatment reduced ghrelin expression in the
      intestinal bulb, and increased serotonergic activity in the telencephalon. In
      summary, our results indicate for the first time in fish that OEA could be
      involved in the regulation of feeding, swimming and lipid metabolism, suggesting
      a high conservation of OEA actions in energy balance throughout vertebrate
      evolution.

PMID- 24855682
TI  - Desiccation resistance reflects patterns of microhabitat choice in a Central
      American assemblage of wandering spiders.
AB  - The lowland rainforest of northeastern Costa Rica harbours an assemblage of large
      wandering spider species belonging to three habitat subguilds: (1) semi-aquatic,
      (2) forest ground dwelling and (3) vegetation dwelling. We hypothesized that
      desiccation resistance should differ among species preferring different
      microhabitats and the associated microclimate. Desiccation resistance was
      assessed by: (1) measuring water loss rates of the spiders under relatively dry
      experimental conditions, and (2) recording desiccation susceptibility, i.e. the
      reactions of the spiders to a relatively dry environment. High water loss rates
      and desiccation susceptibility of the semi-aquatic and forest-ground-dwelling
      subguilds clearly mirrored the relatively humid microclimate of the understory.
      Significantly lower water loss rates and desiccation susceptibility of the
      vegetation-dwelling species reflected the highly variable, often dry and hot
      conditions of the rainforest canopy and forest edge habitats. Vegetation-dwelling
      wandering spiders are therefore physiologically better adapted to dry conditions
      than the semi-aquatic and forest-ground-dwelling species. The results illustrate
      the significance of physiological characteristics for explaining both species
      specific habitat use and, in a larger context, niche partitioning within a
      community.

PMID- 24855684
TI  - Gardnerella vaginalis does not always cause bacterial vaginosis.

PMID- 24855685
TI  - Reply to Hickey and Forney.

PMID- 24855683
TI  - Was low CO2 a driving force of C4 evolution: Arabidopsis responses to long-term
      low CO2 stress.
AB  - The responses of long-term growth of plants under elevated CO2 have been studied
      extensively. Comparatively, the responses of plants to subambient CO2
      concentrations have not been well studied. This study aims to investigate the
      responses of the model C3 plant, Arabidopsis thaliana, to low CO2 at the
      molecular level. Results showed that low CO2 dramatically decreased biomass
      productivity, together with delayed flowering and increased stomatal density.
      Furthermore, alteration of thylakoid stacking in both bundle sheath and mesophyll
      cells, upregulation of PEPC and PEPC-K together with altered expression of a
      number of regulators known involved in photosynthesis development were observed.
      These responses to low CO2 are discussed with regard to the fitness of C3 plants
      under low CO2. This work also briefly discusses the relevance of the data to C4
      photosynthesis evolution. 

PMID- 24855687
TI  - Human rights and health care exchanges: Affordable Care Act's antidiscrimination
      provisions.

PMID- 24855686
TI  - Enhanced therapeutic efficacy of combined use of sorafenib and transcatheter
      arterial chemoembolization for treatment of advanced hepatocellular carcinoma.
AB  - OBJECTIVE: Clinical trials suggest that combining transcatheter arterial
      chemoembolization with sorafenib in patients with advanced hepatocellular
      carcinoma shows a superior safety and tolerability profile. Our study aimed to
      retrospectively analyze the utility and prognostic factors of this combined
      therapy in these patients. METHODS: Patients with advanced hepatocellular
      carcinoma, treated by transcatheter arterial chemoembolization and sorafenib
      subsequently, between February 2010 and September 2012 in our hospital, were
      retrospectively analyzed. After sorafenib treatment for 12 weeks, abdominal
      enhanced computed tomography or magnetic resonance imaging was used to evaluate
      short-term outcomes and clinical benefit rate. Overall survival and adverse
      events were recorded during follow-up. Univariate and multivariate analyses were
      used to identify relationships between baseline characteristics and overall
      survival. RESULTS: Fifty-one advanced hepatocellular carcinoma patients were
      included. Common adverse events for sorafenib were hand-foot skin reaction,
      alopecia, diarrhea, anorexia and fatigue. The clinical benefit rate was 64% and
      the median survival time was 7.5 months. Median survival of patients with and
      without portal vein tumor thrombi was 6.0 months and 10.3 months (P < 0.001),
      respectively. Median survival of patients with cholinesterase >=5000 U/l and <
      5000 U/l was 10.6 months and 6.1 months (P < 0.001), respectively. Multivariate
      analysis identified the presence of portal vein tumor thrombi and low
      cholinesterase level as independent negative predictors of survival. CONCLUSIONS:
      Combining sorafenib and transcatheter arterial chemoembolization was safe and
      effective for advanced hepatocellular carcinoma patients with extrahepatic spread
      but without portal vein tumor thrombi. Portal vein tumor thrombi and
      cholinesterase level are independent predictors of prognosis following this
      combined therapy.

PMID- 24855688
TI  - Perceptions of emtricitabine-tenofovir in HIV PrEP.

PMID- 24855689
TI  - What is life like for HIV-infected Latinos living in Arkansas?

PMID- 24855690
TI  - Best diet for HIV-infected individuals is not a one-size-fits-all.

PMID- 24855691
TI  - Menopause. HIV-positive women need to be screened for anxiety.

PMID- 24855692
TI  - Many teen, young adult males wait too long to seek HIV treatment.

PMID- 24855694
TI  - Parents influence likelihood of STDs.

PMID- 24855693
TI  - Pornography. Adult film company loses Cal/OSHA appeal on condom use.

PMID- 24855695
TI  - Employment. Court says employee may proceed with FMLA retaliation claims.

PMID- 24855696
TI  - Record showed inmate received adequate HIV care in prison.

PMID- 24855697
TI  - Immigration. Court affirms denial of woman's petition seeking asylum.

PMID- 24855698
TI  - SSI. HIV, pulmonary condition did not render woman disabled.

PMID- 24855699
TI  - T-cell modification.  Cells genetically modified to resist HIV in 12 people.

PMID- 24855700
TI  - Treatment.  Researchers predict ACA will improve HIV outcomes for many.

PMID- 24855702
TI  - Men, childless, more likely to stop HIV treatment in S. Africa.

PMID- 24855703
TI  - Employment.  Worker who said he was fired for HIV may proceed with suit.

PMID- 24855701
TI  - Transmission.  Study finds that HIV more often acquired outside community.

PMID- 24855704
TI  - SSI.  ALJ did not err in finding that woman was not disabled.

PMID- 24855705
TI  - Company showed adequate reasons for terminating benefits.

PMID- 24855706
TI  - Prison was not indifferent to needs of HIV-positive inmate.

PMID- 24855707
TI  - Letters. About the decision by the Court of Ferrara on the supposed connection
      between the role of vaccination and the genesis of non-Hodgking Lymphoma.

PMID- 24855708
TI  - Proceedings of the 4th Intercontinental Cooperative ITP Study Group (ICIS),
      September 2012, Montreux, Switzerland.

PMID- 24855709
TI  - Medicare program; Contract Year 2015 Policy and Technical Changes to the Medicare
      Advantage and the Medicare Prescription Drug Benefit Programs. Final rule.
AB  - The final rule will revise the Medicare Advantage (MA) program (Part C)
      regulations and prescription drug benefit program (Part D) regulations to
      implement statutory requirements; improve program efficiencies; and clarify
      program requirements. The final rule also includes several provisions designed to
      improve payment accuracy.

PMID- 24855711
TI  - Do you use your voice to its best ability in promoting the importance of your
      role in perioperative practice?

PMID- 24855710
TI  - Reply from the author.

PMID- 24855712
TI  - The good, the bad and the ugly!

PMID- 24855713
TI  - A safe method to prevent visor fogging and allow visual aids.

PMID- 24855714
TI  - New recommendations to further improve surgical safety.

PMID- 24855715
TI  - NHS staff feel more enthusiastic and engaged at work.

PMID- 24855716
TI  - Reducing same day cancellations due to patient related factors in elective
      orthopaedic surgery: experience of a centre in the UK.
AB  - Cancellations on the day of surgery represent a major wastage of resources and
      can impose significant distress on patients. Minimising same day cancellations
      can improve cost effectiveness of operating theatre running. The aim of the study
      was to determine the impact of administering a questionnaire, by phone to
      elective orthopaedic patients, the week prior to surgery. This questionnaire was
      aimed at identifying factors that could lead to same day cancellation for patient
      related reasons. The questionnaire was administered to elective orthopaedic
      patients over a nine month period. The rate of same day cancellations due to
      patient related reasons in this cohort (Phase 2) was compared with a previous
      cohort assessed over a five month period when the questionnaire was not in place
      (Phase 1). Administering the questionnaire reduced the same day cancellations due
      to patient reasons from 11 out of 110 (10%) to 2 out of 118 (1.60%) (p = 0.01).
      Theatre wastage in terms of national tariff lost due to cancellations was reduced
      from 25,881 sterling pounds to 1,650 sterling pounds (p<0.001). The study
      concludes that administering a questionnaire aimed at addressing patient related
      reasons can significantly reduce same day cancellations.

PMID- 24855717
TI  - Strategies for the management and avoidance of hypothermia in the perioperative
      environment.
AB  - This Open Learning Zone article outlines the necessity of monitoring temperature
      for patients undergoing surgical procedures with either general or local
      anaesthesia. An overview of the physiology of heat production and loss in the
      human body, and temperature as thermal measurement is given.

PMID- 24855718
TI  - A critical guideline appraisal overview: Choice Framework for local Policy and
      Procedures (CFPP) 01-06 Decontamination of flexible endoscopes 2013. Part 1:
      Policy and management and Part 3: Operational management manual.

PMID- 24855719
TI  - Compression bandaging improves mobility following total knee replacement in an
      enhanced recovery setting.
AB  - The early functional outcome was assessed in 180 patients undergoing total knee
      replacement (TKR) using compression bandaging versus standard crepe bandaging.
      Patients with a compression bandage following TKR were significantly more likely
      to be discharged with a walking stick (p=0.002) and less likely to be discharged
      with a rollator frame (p=0.001). These patients demonstrated an improved range of
      knee flexion and ability to straight leg raise at discharge.

PMID- 24855720
TI  - Edward Cock: Cock's 'peculiar tumour'.
AB  - I must first apologise to my readers for including in this series a condition
      which I have never personally seen in 40 years of general surgery, nor, I
      believe, have any of the readers of this article. My excuse is that the condition
      has such a charming name and that the surgeon, Edward Cock, was such an
      interesting character.

PMID- 24855721
TI  - The risks of undiagnosed cancer vs the theoretical risks of radiation exposure.

PMID- 24855722
TI  - A different view of the 340B program.

PMID- 24855723
TI  - The authors respond.

PMID- 24855724
TI  - Tobacco control since the 1964 Surgeon General's Report: reflecting back and
      looking forward.

PMID- 24855725
TI  - Pertuzumab and its accelerated approval: evolving treatment paradigms and new
      challenges in the management of HER2-positive breast cancer.
AB  - The addition of trastuzumab, a monoclonal antibody to human epidermal growth
      factor receptor 2 (HER2), to standard chemotherapy in patients with HER2-positive
      breast cancer has resulted in major improvements in breast cancer outcomes,
      including improved survival, in both the adjuvant and metastatic settings.
      However, some patients experience disease relapse despite adjuvant trastuzumab
      containing therapy, and resistance to trastuzumab develops in the majority of
      patients in the metastatic setting. An understanding of the molecular mechanisms
      underlying trastuzumab resistance has aided the development of novel HER2
      targeted therapies. In June 2012, the HER2 dimerization inhibitor pertuzumab was
      approved by the US Food and Drug Administration (FDA) for use with chemotherapy
      and trastuzumab in the first-line treatment of metastatic HER2-positive breast
      cancer. In September 2013, accelerated approval was granted for use of pertuzumab
      in the neoadjuvant setting, representing a landmark decision by the FDA. This
      article discusses the development of pertuzumab to date, with a particular focus
      on the accelerated approval decision. We highlight the need to identify reliable
      biomarkers of sensitivity and resistance to HER2-targeted therapy, which would
      make possible the individualization of treatment for patients with HER2-positive
      breast cancer.

PMID- 24855726
TI  - Neoadjuvant pertuzumab: the exception that proves the rule?

PMID- 24855728
TI  - Metastatic relapse after initial clinical stage I testicular Leydig cell tumor.

PMID- 24855727
TI  - Pertuzumab: increasing the options.

PMID- 24855729
TI  - Management of centrally located non-small-cell carcinoma.
AB  - Treatment optimization for centrally located lung cancers requires special
      considerations for determining resectability and patient selection. Evaluation
      involves an experienced multidisciplinary team performing careful clinical and
      invasive-disease staging to identify the best management approach and ascertain
      the need for multimodality therapy. Preoperative imaging alone is often
      inaccurate in its ability to determine whether the patient is at an advanced
      clinical T stage that might preclude curative surgical resection. Therefore,
      other modalities are often necessary to complete the clinical staging. In the
      absence of irrefutable evidence of unresectability, however, surgical exploration
      should be undertaken with curative intent. Long-term outcomes can be favorable in
      select patients, and most of the procedures, including complex reconstructions,
      can be performed with acceptable morbidity and mortality.

PMID- 24855730
TI  - Meeting the challenges of centrally located non-small-cell lung cancer.

PMID- 24855731
TI  - Invasive staging and aggressive surgical resection: essential to management of
      central NSCLC.

PMID- 24855733
TI  - Addressing the challenge of managing radiation use in medical imaging: paradigm
      shifts and strategic priorities.

PMID- 24855732
TI  - Curbing potential radiation-induced cancer risks in oncologic imaging:
      perspectives from the 'image gently' and 'image wisely' campaigns.
AB  - Medical imaging that uses ionizing radiation, such as CT, radiography, nuclear
      medicine, and fluoroscopy, is a cornerstone of the care of oncology patients and
      provides great benefit. Ionizing radiation at high doses is a known
      carcinogen.The exact degree of the risk of carcinogenesis from the lower doses of
      ionizing radiation used in medical imaging is less clear. The purpose of this
      review is to provide the oncology community with knowledge about the doses used
      in medical imaging, radiation-induced cancer risks from imaging, considerations
      to keep in mind when balancing imaging benefits and risks in pediatric and adult
      oncologic settings, dose reduction strategies, and the "Image Gently" and "Image
      Wisely" campaigns; the latter campaigns facilitate the translation of existing
      evidence into best practices for providers and patients.

PMID- 24855734
TI  - ALARA: in radiation oncology and diagnostic imaging alike.

PMID- 24855735
TI  - Bulky mediastinal classical Hodgkin lymphoma in young women.

PMID- 24855737
TI  - [Analysis of human tissue samples for volatile fire accelerants].
AB  - In police investigations of fires, the cause of a fire and the fire debris
      analysis regarding traces of fire accelerants are important aspects for forensic
      scientists. Established analytical procedures were recently applied to the
      remains of fire victims. When examining lung tissue samples, vapors inhaled from
      volatile ignitable liquids could be identified and differentiated from products
      of pyrolysis caused by the fire. In addition to the medico-legal results this
      evidence allowed to draw conclusions as to whether the fire victim was still
      alive when the fire started.

PMID- 24855736
TI  - [Recreational boating accidents--Part 2: Causes of accidents and deaths].
AB  - According to Naeve, forensic medicine also deals with medical topics concerning
      accidents associated with watercrafts. This field is not limited to the open sea
      but also refers to rivers and lakes. In the presented study, fatal boating
      accidents were investigated over a period of four decades. The majority of the
      victims died from hypothermia and drowning. The article points out the difficulty
      to prove hypothermia in cases with a short survival time. Medical expert opinions
      on deaths due to boating accidents must not ignore the results of the technical
      and nautical investigations--the more so as the hydrometeorological situation may
      be crucial for the outcome. Too little attention is still paid to circulatory
      shock occurring in connection with the pathophysiology of hypothermia and
      drowning, although it may have a decisive influence on the effectiveness of
      rescue measures. The final assessment of fatalities in users of watercrafts
      should always be left to experienced specialists.

PMID- 24855738
TI  - [The problem of highlights in forensic photography].
AB  - A problem of forensic photography, especially when using direct flashlight, is
      the appearance of highlights on wet or shiny surfaces because of light
      reflections. Highlights can cause considerable difficulties if they interfere
      with relevant findings, because in a flare image information is reduced. Forensic
      literature describes several procedures to prevent the formation of highlights,
      which we compared to each other using flashlight in order to find the most
      effective and practicable method for reducing reflections. First, bounce flash
      photography can completely prevent flashlight flares on shiny surfaces such as
      putrefied bodies. Second, powdering such surfaces with rice powder can eliminate
      disruptive flares even when using direct flashlight but causes visible artefacts
      when using higher magnifications. As our study showed, bounce flash photography
      is an easy way to reduce highlights on photographs without the application of
      complex techniques or methods that may even alter relevant findings.

PMID- 24855739
TI  - ["Piggyback" shot: ballistic parameters of two simultaneously discharged airgun
      pellets].
AB  - Green and Good reported an uncommon case of homicide committed with an air rifle
      in 1982 (Am. J. Forensic Med. Pathol. 3: 361-365). The fatal wound was unusual in
      that two airgun pellets were loaded in so-called "piggyback" fashion into a
      single shot air rifle. Lack of further information on the ballistic
      characteristics of two airgun pellets as opposed to one conventionally loaded
      projectile led to this investigation. The mean kinetic energy (E) of the two
      pellets discharged in "piggyback" fashion was E = 3.6 J and E = 3.4 J,
      respectively. In comparison, average kinetic energy values of E = 12.5 J were
      calculated for conventionally discharged single diabolo pellets. Test shots into
      ballistic soap confirmed the findings of a single entrance wound as reported by
      Green and Good. While the ballistic background of pellets discharged in
      "piggyback" fashion could be clarified, the reason behind this mode of shooting
      remains unclear.

PMID- 24855740
TI  - ["Biastophilia"--rape as a form of paraphilia?].
AB  - Rape is primarily regarded as a crime against sexual integrity. If rape is the
      only way for an individual to get sexual satisfaction, it meets the criteria of
      paraphilia, i.e. a disorder of sexual preference. The correct technical term is
      "biastophilia". The author investigates the evolutionary origins of this deviant
      form of copulation behavior, whose crucial characteristic is breaking the will of
      the sexual object. He shows that in a primeval environment this type of mating
      behavior may have been a promising strategy to pass on one's genes to the next
      generation. Thus, the behavioral pattern of raping had the chance to become
      widely spread in spite of its social undesirability.

PMID- 24855741
TI  - [Prescription against the health care crisis].

PMID- 24855742
TI  - [Effect of mindfulness studied in U.S. government agency report. Small to
      moderate effect in depression, anxiety and pain syndromes].

PMID- 24855743
TI  - [A lot of news on the fertility front].

PMID- 24855744
TI  - [Private egg bank to protect fertility against aging].

PMID- 24855745
TI  - [Preserved fertility despite disease with a risk of infertility in young age].

PMID- 24855746
TI  - [Close monitoring is required before and during pregnancy in Turner syndrome].

PMID- 24855747
TI  - [Surrogate motherhood--experienced team should follow the entire process].

PMID- 24855748
TI  - [Transplantation of the uterus still at the experimental stage].

PMID- 24855749
TI  - [Questionable effect of antiviral therapy in malignant brain tumors].

PMID- 24855750
TI  - [Inadequate IT security is a potential threat to the integrity and patient
      safety].

PMID- 24855751
TI  - [It is both permitted and forbidden to drive after taking drugs].

PMID- 24855752
TI  - [Sweden should be a model for safety and environment in the mining industry].

PMID- 24855753
TI  - [Watch out for the sneaky relatives of the potato].

PMID- 24855754
TI  - [John Kayser. From musician to nurse].

PMID- 24855756
TI  - [School-based sexual health services].

PMID- 24855755
TI  - [Diagnosis of genetic disorders. The first pediatric genomics center of Canada].

PMID- 24855757
TI  - [Neonatal resuscitation kit].

PMID- 24855758
TI  - [Organ donation is not to be rushed].

PMID- 24855759
TI  - [Hypothyroidism. The silent epidemic].

PMID- 24855760
TI  - [What's your method of peripheral intravenous catheterization?].

PMID- 24855761
TI  - [Falls from windows in children. The cause of serious trauma in children].

PMID- 24855763
TI  - [Summer heat waves. Take care in periods of extreme heat].

PMID- 24855762
TI  - [West Nile virus is always in town!].

PMID- 24855764
TI  - [Therapeutic hypothermia. Nursing care and clinical surveillance in three
      phases].

PMID- 24855765
TI  - [Using the AINEES mnemonic. Part 2. The history of Mrs. Rose].

PMID- 24855766
TI  - [Teriflunomide (Aubagio). New treatment for multiple sclerosis].

PMID- 24855768
TI  - [Launching of the Academy of Medicine Foundation].

PMID- 24855767
TI  - [On mission in Afghanistan. Jennifer Simard in the country of feudal war lords
      and the Taliban].

PMID- 24855769
TI  - [Drug shortages: a daily problem which needs long-term solutions].

PMID- 24855770
TI  - [Vaccination coverage against HPV is still too low in France!].

PMID- 24855771
TI  - [MERS-CoV: a new virus from Saudi Arabia].
AB  - Since about a year, a new pulmonary pathology occurred in Saudi Arabia and some
      cases are imported in Europa. This disease is due to a coronavirus named MERS-CoV
      (Middle East Respiratory Syndome Coronavirus). The main symptoms are fever,
      pulmonary and digestive troubles, with a risk of nosocomial transmission and a
      mortality of about 42%. The reservoir is probably the dromedary camel and the bat
      is the vector. There is no specific treatment or vaccine.

PMID- 24855772
TI  - [Post-cementoplasty pulmonary embolism].

PMID- 24855773
TI  - [Cognitive impairment of alcohol-dependent subjects].
AB  - Chronic excessive alcohol consumption induces multiple brain damages. Secondary
      cognitive disorders include executive functions, episodic memory and visuospatial
      capacities. The severity of these alcohol induced disorders may vary between sub
      clinical manifestations (that may, nevertheless, interfere with medical
      management) and more important ones like Korsakoff syndrome or dementia. The
      latter are usually irreversible but many of these manifestations are potentially
      reversible with persistent abstinence. It therefore appears of particular
      importance to clearly define neuropsychological management in order to identify
      and evaluate the type and severity of alcohol-related cognitive disorders. The
      patients may then be offered rehabilitation for these cognitive impairments. This
      is the first step of a complete addiction program based especially on cognitive
      behavioral therapies.

PMID- 24855774
TI  - [Arachnoid cyst].

PMID- 24855775
TI  - [Elements of a bibliography in 10 lessons: # 4. Bibliographic databases].

PMID- 24855776
TI  - [Not Available].

PMID- 24855777
TI  - [Initial treatment of type 2 diabetes: metformin also for the Chinese!].

PMID- 24855778
TI  - [Not Available].

PMID- 24855779
TI  - [Not Available].

PMID- 24855780
TI  - [Psychiatric disorders in children and adolescents. Prevention and detection,
      early orientation, maintain socialization].

PMID- 24855781
TI  - [Early detection of mental disorders in infants or children].
AB  - Early detection of babies or children mental disorders enables specific diagnosis
      and care in the very early life of the distressed children. It is critical to
      make all physicians able to identify early signs. Autism, depression, anguage and
      learning disorders are pathologies whose early diagnosis enables early care thus
      limiting the negative impact on child and family lives. In the specific context
      of child abuse, it is our duty to detect alarming signs as soon as possible to
      fully protect the abused baby or child.

PMID- 24855782
TI  - [Pervasive developmental disorders].
AB  - Pervasive developmental disorders (PDD-ICD10), covering roughly the same entity
      as the autism spectrum disorders (ASD DSM-IVTR and DSM-V) include a heterogeneous
      clinical reality. PDD develop in childhood and are characterized by alterations
      in socialization, communication and behavior disorders with stereotypies and
      repetitive movements. Autism is included in PDD and has led to many debates in
      France and to the publication of recommendations and government plans, in recent
      years. We propose in this article to review the current knowledge of this topic.

PMID- 24855783
TI  - [Childhood and adolescent depression].
AB  - Depressive disorders are present at every age. However, specific clinical and
      therapeutic characteristics are described for depressive disorders during
      childhood. Moreover, psychopathological and therapeutic approach must take in
      account the child's development and environment. In this article, we will review
      depression among babies, childhood depression and adolescent depression with much
      consideration for developmental and relational perspective. We also discuss the
      treatment and especially the use of antidepressants in clinical practice.

PMID- 24855784
TI  - [Bipolar disorder in adolescence].
AB  - Juvenile mania is a concept widely developed but also highly debated since the
      1990s. In the heart of this debate, Severe Mood Dysregulation (SMD) and "Temper
      Dysregulation disorder with Dysphoria" (recently integrated in DSM-5) showed
      their interest. Actually, the objective is to distinguish two clinical phenotypes
      in order to avoid confusion between (1) what would raise more of mood
      dysregulation with chronic manic like symptoms, and (2) bipolar disorder type I
      with episodic and acute manic episodes. Therapeutic stakes are major. In
      adolescents, even if DSM adult diagnostic criteria can be used and bipolar
      disorder type I clearly established, differential diagnostic at onset between
      acute manic episode and schizophrenia onset remain sometimes difficult to assess.
      Furthermore, it is crucial to better assess outcome of these adolescents, in
      terms of morbidity and potential prognosis factors, knowing that a younger age at
      onset is associated with a poorer outcome according to several adult studies.
      Therapeutic implications could then be drawn.

PMID- 24855785
TI  - [Schizophrenic disorders in adolescence].
AB  - This article provides a brief overview of Early Onset Schizophrenia (EOS).
      Schizophrenia is a severe, devastating and common psychiatric disorder (around 1%
      of general population). EOS is defined as onset before 18 years with a Childhood
      Onset Schizophrenia (COS) sub-category beginning before 13. COS is rare
      representing 1% of all schizophrenia, with a prevalence of 1 in 10000 births.
      Prevalence increases remarkably during adolescence with 4% of all schizophrenic
      disorders before 10 and 12-34% before 18. DSM-IV criteria for EOS are the same as
      for adult onset schizophrenia. Interestingly, compared to cases with adult onset,
      EOS shows the following characteristics: 1) it is more frequent in males; 2)
      onset is more often insidious; 3) minor neurological signs, negative symptoms and
      catatonia are more frequent; 3) a history of developmental problems (ranging from
      minor motor coordination disorder to autism spectrum disorders) occurs in up to
      50% of the cases; 4) the disease process has a greater impact on cognition and
      brain anatomic markers; 5) comorbid organic and genetic risk factors, including
      mental retardation, are more prevalent. Gold standard treatments are
      antipsychotic medications, which are approved by administration until 13 years
      old in France. It is of particular importance to search for side effects which
      may have different profile in pediatric populations.

PMID- 24855786
TI  - [Adolescent behavioral disorders].
AB  - Adolescence is a period of physical and mental transition between childhood and
      adulthood, two supposedly quieter periods. Puberty and social pressures generate
      painful psychic conflicts even for a subject without particular problem.
      Behavioral disorders of adolescents are numerous and heterogeneous. It is
      oppositional defiant disorder, conduct disorder, hyperactive disorder with
      attention deficit which often begin during childhood to evolve negatively in
      adolescence. Eating disorders, addictive disorders, self-mutilation and
      scarification are also found. Therapeutic management should be multimodal and
      involve different actors in the health, education and social areas.

PMID- 24855787
TI  - [Adolescent addictive behaviors].
AB  - Adolescence is a period with a specific risk to develop addictive behaviours.
      During this key period, addictions can be at the root of very damaging
      consequences, both on the health and social sides, which is nowadays a public
      health issue. Paradoxically, teenagers are often not requesting for aid and
      access aid with difficulty. So, first aid operators play a central role in
      teenagers' care, since they can detect precociously at-risk teenagers and
      orientate them to specialized care if necessary.

PMID- 24855788
TI  - [Somatoform disorders in adolescence].
AB  - Somatoform disorders are fairly common in adolescents. These disorders are
      frequently met by all professionals like pediatricians, neurologists and general
      physicians. Studies on adolescence encountered bias to evaluate frequency of
      these disorders because of variations in the diagnostic criteria used by
      different workers and diversity of units concerned. Actually, there is no
      consensus about taking care these patients. Paediatricians remain the first step
      and link for the care which is often complicated and needs multidisciplinary
      approach. The recognition of somatoform disorders requires two complementary
      diagnostic processes in order to propose a fitted treatment for adolescents for
      whom symptoms always are the reflection of a suffering that has to be identified,
      evaluated and cared.

PMID- 24855789
TI  - [Organization of psychiatric care for children and adolescents].

PMID- 24855791
TI  - [Menometrorrhagia].
AB  - Menometrorrhagia is a frequent cause of medical consulting. After exclusion of
      pregnancy, main aetiologies are the uterine (polyp, myoma, adenomyosis, cancer)
      or adnexial abnormality (ovarian cyst or cancer), the disorders of hemostasis
      (Willebrand...), the dysfunctional uterine bleeding. A clinical examination is
      necessary to provide an accurate diagnosis and find complications such as
      anaemia. Pelvic ultrasound examination and endometrial biopsy are required to
      eliminate endometrial cancer. The treatment of menometrorrhagia consists of
      symptomatic treatment (tranexamic acid, levonorgestrel intrauterine device) and
      specific treatment of its cause (hysteroscopic resection of myom, polyp,
      endometrectomy, hysterectomy).

PMID- 24855790
TI  - [Psychotropic medication in children and adolescents].

PMID- 24855792
TI  - [Uterine fibroids].
AB  - The uterine fibroid is a benign tumour. The prevalence, in all the population, is
      50% for european women and 80% for black women. 30% of fibroids are symptomatic.
      The new FIGO classification gives 7 positions (0 to 7), submuccus (0, 1, 2),
      interstitial (3, 4, 5), subserous (6, 7). Diagnosis is performed by 2D and 3D
      ultrasound which could be associated by hysterosonography. Hysteroscopy and MRI
      could be proposed. Hysterectomy is the main treatment, if possible by vaginal or
      laparoscopic way. Conservative treatment (myomectomy) could be realized by
      hysteroscopic, laparoscopic way or laparotomy for patients who desire to preserve
      fertility. Arteries embolisation is an alternative to hysterectomy or myomectomy
      for patients without desire of pregnancy. Preoperative treatments by GnRH agonist
      or SPRM like ulipristal acetate treat anaemia, decrease the myoma volume and
      could modify the therapeutic strategy.

PMID- 24855794
TI  - [Adenomyosis].

PMID- 24855793
TI  - [Endometriosis].
AB  - Endometriosis is a benign disorder affecting 10 to 15% of women of reproductive
      age. It is defined by the presence of endometrium-like tissue outside the uterus.
      There are three different entities of endometriosis: superficial endometriosis,
      ovarian endometriotic cyst and deep infiltrating endometriosis. The main clinical
      features are dysmenorrhea, chronic pelvic pain and dyspareunia. Endometriosis is
      also responsible for infertility. Transvaginal sonography and magnetic resonance
      imaging are required to assess mapping of endometriotic lesions. Medical
      therapies based on progestins or combined oral contraceptives allow to relief
      symptoms. Despite a relative efficacy of medical treatment or in case of
      infertility, surgery is necessary preferentially in specialized centers.

PMID- 24855795
TI  - [What students for what doctors?].

PMID- 24855796
TI  - [Testicular tumors].

PMID- 24855797
TI  - [Movement disorders].

PMID- 24855798
TI  - [Wilson Disease].

PMID- 24855799
TI  - [Specific aspects of palliative care in the ICU].

PMID- 24855801
TI  - [In the time of the "Medical Study Tours"].

PMID- 24855800
TI  - [Amyloidosis].

PMID- 24855802
TI  - Shifting the paradigm: an academic public-private partnership to form a virtual
      nurse managed clinic.

PMID- 24855804
TI  - Core communication competencies in patient-centered care.
AB  - Effective communication between the patient and nurse is an essential requirement
      for nursing practice and for patient-centered care. Nursing faculty that teach in
      undergraduate and graduate nursing programs play a significant role in preparing
      the nursing workforce to communicate effectively and provide patient-centered
      care. Patient-centered care, interprofessional collaboration, and informatics are
      necessary knowledge, skills, and attitudes for nurses across educational levels
      in order to meet the needs of patients, and improve the quality and safety of the
      health care system environment. The focus of this article is to provide
      information on core nursing competencies for effective communication and to
      discuss communication tools used in patient-centered care, interprofessional
      collaboration, and informatics.

PMID- 24855803
TI  - A pilot study of RN-BSN completion students' preferred instructor online
      classroom caring behaviors.
AB  - Definitions of caring include the global concept of showing concern and empathy
      of others. This may be especially true in the online classroom in the absence of
      face to face interactions. This quantitative study focused on RN-BSN completion
      students' preferred online instructor caring behaviors. Online RN-BSN students (N
      = 100) were invited to participate in the study. The research question was: What
      are historically black colleges universities nursing students' preferred
      instructor caring behaviors in the online classroom? All of the respondents (N =
      48) agreed that an instructor can create a caring online learning environment,
      while the vast majority agreed that the presence of a caring environment
      influenced their success in the course. As ranked by the respondents the three
      most important items in creating a caring online learning environment were
      instructors': 1) attention to detail in organization and clarity, 2) prompt and
      detailed feedback to assignments, and 3) prompt response to students' questions.

PMID- 24855805
TI  - The fundamentals of integrating service in a post-licensure RN to BSN program.
AB  - Integrating service in a post-licensure registered nurse to bachelor of science
      in nursing (RN to BSN) program provides licensed registered nurse (RN) students
      the opportunity to learn, develop, and experience different cultures while
      serving the community and populations in need (McKinnon & Fitzpatrick, 2012).
      Service to the community, integrated with academic learning can be applied in a
      wide variety of settings, including schools, universities, and community faith
      based organizations. Academic service-learning (ASL) can involve a group of
      students, a classroom, or an entire school. In the RN to BSN program, the authors
      use a student-directed service learning approach that integrates service-learning
      throughout the curriculum. RN students are introduced to service-learning at
      program orientation prior to the start of classes and receive reinforcement and
      active engagement throughout the curriculum. The students and volunteer agencies
      receive and give benefits from the services provided and the life lessons gained
      through mentorship, education, and hands-on experiences.

PMID- 24855806
TI  - An experiential Cardiovascular Health Education Program for African American
      College Students.
AB  - OBJECTIVE: To pilot test a culturally specific and developmentally appropriate
      curriculum for African-American college students that included self and family
      assessment to increase awareness of their risk of cardiovascular disease (CVD).
      METHODS: Students were recruited from a historically Black university to
      participate in small group workshops focusing to increase their knowledge of
      their family history of CVD as well as reducing CVD risks. Focus groups were
      conducted to determine the effectiveness and ways to improve to the intervention.
      RESULTS: Positive findings were found regarding program efficacy, increased
      understanding of their family history and strategies to reduce their own risk of
      CVD. CONCLUSION: Small group experiential workshop approach can be effective in
      helping African- American college students understand risk and establish healthy
      heart habits aimed at decreasing risk of coronary heart disease.

PMID- 24855807
TI  - Health disparities: what can we do?

PMID- 24855808
TI  - In memorian. Carol A. "Pat" Patsdaughter, PhD, CNE, ACRN.

PMID- 24855809
TI  - "Take your own path": minority leaders encountering and overcoming barriers in
      cultural community centers.
AB  - Minority leaders face workplace issues not experienced by white leaders including
      lack of support, discrimination, racism, and stereotyping. The purpose of this
      study was to explore how racial/ethnic minority leaders encountered and overcame
      barriers as leaders of cultural community centers. Three racial/ethnic minority
      executive directors of cultural community centers located in a Midwestern city
      were interviewed and their responses were hand-coded to develop themes. Six
      themes emerged from this process: finding "inspiration", "developing thick skin",
      "stereotypes", "damage from within", "take your path", and "hope". Their stories
      help us understand the complexities of inter-racial relations in the workplace.

PMID- 24855810
TI  - Latinas' attitudes about cervical cancer prevention: a meta-synthesis.
AB  - Latina women are almost twice as likely to die from cervical cancer as Caucasian
      women. In response to this disparity, qualitative study has been devoted to this
      topic. In order to generalize knowledge, insights gleaned through qualitative
      research methodology may be integrated through meta-synthesis, a methodology that
      has developed in nursing and related health sciences. The primary purpose of this
      meta-synthesis was to obtain information about Latinas' knowledge, attitudes, and
      perceptions regarding cervical cancer and its screening. After applying inclusion
      criteria, nine studies were located. Results were organized around four areas of
      inquiry that cross-cut primary studies: 1) Latina participants' knowledge of
      cervical cancer and its prevention; 2) barriers for regular cervical cancer
      screening; 3) facilitators that encouraged such screening; and 4) recommendations
      on how to provide screening for Latina women. Findings indicated that culturally
      appropriate education and improving accessibility to health care were the most
      important overall themes for future efforts to improve screening rates among
      Latinas in the United States.

PMID- 24855812
TI  - A cultural contracts perspective: examining American Indian identity negotiations
      in academia.
AB  - Education has played a central role in identity confusion, and to this day, it is
      used to assimilate American Indians. For those American Indians who persist
      through doctoral degrees and enter academe, resisting assimilation is especially
      risky and often tiresome. In this conceptual exploration of identity, Cultural
      Contracts theory serves to illuminate the path of the American Indian academic
      journey. Although never applied in an American Indian context, cultural contracts
      theory may provide a bridge between the seemingly disparate strains of identity
      research and leave us with a sense of scope and potential for the theory's
      application.

PMID- 24855811
TI  - Perceptions of culturally competent diabetes management in a primary care
      practice.
AB  - To evaluate whether clinicians consider the impact of culture on diabetes
      management, a survey was mailed to 300 randomly selected patients > or = 50 years
      with type 2 diabetes and 153 surveys were returned. Data were correlated with A1C
      values. African Americans (AA) and non-Hispanic whites (NHW), (91.9%, 97.0%)
      respectively, reported clinicians discussed benefits of controlling blood sugar
      but did not discuss effects of cultural issues on glucose control (< or = 50%).
      AAs perceived clinicians were more accommodating of their cultural preferences
      than did NHWs (49.2% versus 30.6%) (P < .05). Females (51.9%) (P < .01) reported
      that clinicians acknowledged the importance of their cultural beliefs with a
      slightly higher percentage for African American females (54.8%) versus non
      Hispanic White females (48.6%). Understanding the patient's and clinician's views
      of cultural beliefs as they relate to diabetes self-management can provide
      perspectives to guide care.

PMID- 24855813
TI  - Korean working mothers' parenting style in Korea and in the United STates: a
      qualitative comparative study.
AB  - The purpose of this study was to explore the similarities and differences of
      cultural influences on the parenting styles of Korean working mothers who live in
      South Korea versus Korean American working mothers living in the U.S. Four major
      themes were identified: (a) expression of affection for children, (b) parental
      control, (c) feelings for children, and (d) feelings for themselves. The findings
      indicate that acculturation to the American culture affected the Korean American
      working mothers to grant higher self-regulation to their children and to have
      more positive feelings for their children and themselves.

PMID- 24855814
TI  - Bringing medicine together--the team approach.

PMID- 24855815
TI  - Crossing the Rubicon.

PMID- 24855816
TI  - Do you still live in the same community?

PMID- 24855817
TI  - Grassroots advocacy: what is it?

PMID- 24855818
TI  - Practice of medicine: a fragmented community. Searching for ways to come
      together.

PMID- 24855820
TI  - Why physicians misprescribe.

PMID- 24855819
TI  - SGR repeal and state payment reform initiative: eerily similar.

PMID- 24855821
TI  - PEGylation--a well-proven strategy for the improvement of recombinant drugs.
AB  - Protein and peptide drugs hold great promise as therapeutic agents. But there are
      shortcomings: Many recombinant proteins are quickly degraded by proteolytic
      enzymes or are rapidly cleared by kidney filtration resulting in a short
      circulating half-life. Additionally they are prone to be recognized by the immune
      system resulting in the generation of neutralizing and non-neutralizing
      antibodies. PEGylation, a process by which polyethylene glycol chains are
      attached to protein and peptide drugs, can overcome these and other shortcomings.
      By increasing the molecular mass of proteins and peptides and shielding them from
      proteolytic enzymes, PEGylation primarily improves pharmacokinetics and helps to
      prevent adverse drug reactions.

PMID- 24855822
TI  - Preparation, characterization and in vitro evaluation of a polyvinyl
      alcohol/sodium alginate based orodispersible film containing sildenafil citrate.
AB  - In this work, we developed a sildenafil citrate (SC)-loaded polyvinyl alcohol
      (PVA)/sodium alginate (ALG-Na) based orodispersible film (ODF) using a solvent
      casting method. Formulation factors such as the type and amount of plasticizers
      and disintegrants were optimized on the basis of characteristics of blank ODF,
      including the disintegration time, elastic modulus (EM) and percentage of
      elongation (E%). SC-loaded ODF with a loading capacity up to 25 mg in an area of
      6 cm2 was prepared and evaluated in terms of mechanical properties,
      disintegration time and dissolution rate. The surface morphology of ODF was
      visualized under a scanning electron microscope (SEM). The physicochemical
      properties of ODF were investigated using X-ray diffraction (XRD), differential
      scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR).
      The blank ODF composed of PVA, polyethylene glycol 400 (PEG 400) and ALG-Na
      (20:5:2, w/w) had a remarkably short disintegration time of about 20 s. However,
      the loading of drug extended the disintegration time (100 s) of ODF, while it
      still maintained satisfactory mechanical properties. SC was homogenously
      dispersed throughout the films and the crystalline form of drug changed, with
      strong hydrogen bonding between the drug and carriers. The PVA/ALG-Na based ODF
      containing SC prepared by the simple solvent casting method might be an
      alternative to conventional SC tablets for the treatment of male erectile
      dysfunction.

PMID- 24855823
TI  - Solution thermodynamics and solubilization behavior of diclofenac sodium in
      binary mixture of Transcutol-HP and water.
AB  - Solution thermodynamics and solubilization behavior of diclofenac sodium (DS) in
      binary mixture of Transcutol-HP and water is not reported in the literature so
      far. Therefore, the aim of the present study was to investigate the solution
      thermodynamics and solubilization behavior of DS in mono-solvents and various
      Transcutol-water mixtures at 298.15-333.15 K. The mole fraction solubility of DS
      was determined by shake flask method and thermodynamic parameters (enthalpies and
      entropies) were calculated with the help of the modified Apelblat model. The
      experimental solubility data of DS in all sample matrices was found to be
      correlated well with the modified Apelblat model with correlation coefficients of
      0.9950-0.9990. Absolute relative deviation was found to be less than 3% in most
      of the Transcutol-water mixtures at each temperature studied. The mole fraction
      solubility of DS was observed to be highest in pure Transcutol (0.139 at 298.15
      K) as compared to pure water and other Transcutol-water mixtures. The enthalpies
      and entropies for DS dissolution were observed as positive values for all
      cosolvent mixtures which indicated that the dissolution of DS is endothermic and
      an entropy-driven process. Based on solubility data, DS was considered as
      sparingly soluble in pure water and freely soluble in Transcutol. These results
      indicated that Transcutol could be used as an alternate of ethanol, propylene
      glycol and polyethylene glycol to enhance aqueous solubility of DS. These
      preliminary studies could be useful in formulation development of DS especially
      in terms of liquid dosage forms and injectable formulations.

PMID- 24855824
TI  - An aquaporin 4 antisense oligonucleotide loaded, brain targeted nanoparticulate
      system design.
AB  - Aquaporins (AQPs), members of the water-channel protein family, are highly
      expressed in brain tissue especially in astrocytic end-feet. They are important
      players for water hemostasis during development of cytotoxic as well as vasogenic
      edema. Increased expression of AQPs is important in pathophysiology of
      neurological diseases such as neuroinflammation and ischemia. Unfortunately,
      there are a few pharmacological inhibitors of AQP4 with several side effects
      limiting their translation as a drug for use in clinical conditions. Another
      therapeutic approach is using antisense oligonucleotides (ASOs) to block AQP4
      activity. These are short, synthetic, modified nucleic acids that bind RNA to
      modulate its function. However, they cannot pass the blood brain barrier (BBB).
      To overcome this obstacle we designed a nanoparticulate system made up of
      chitosan nanoparticles surface modified with PEG and conjugated with monoclonal
      anti transferrin receptor-1 antibody via streptavidin-biotin binding. The
      nanocarrier system could be targeted to the transferrin receptor-1 at the brain
      endothelial capillaries through monoclonal antibodies. It is hypothesized that
      the nanoparticles could pass the BBB via receptor mediated transcytosis and reach
      brain parenchyma. Particle size, zeta potential, loading capacity and release
      profiles of nanoparticles were investigated. It was observed that all types of
      chitosau (CS) nanoparticles had positive zeta potential values and nanoparticle
      particle size distribution varied between 100 and 800 nm. The association
      efficiency of ASOs into the nanoparticles was between 80-97% and the release
      profiles of the nanoparticles exhibited an initial burst effect followed by a
      controlled release. The results showed that the designed chitosan based
      nanocarriers could be a promising carrier system to transport nucleic acid based
      drugs to brain parenchyma.

PMID- 24855825
TI  - The MEK1/2 inhibitor U0126 reverses imatinib resistance through down-regulating
      activation of Lyn/ERK signaling pathway in imatinib-resistant K562R leukemia
      cells.
AB  - Chronic myelogenous leukemia (CML) is triggered by the constitutively activated
      BCR-ABL oncoprotein and multiple downstream signaling pathways, including the
      Raf/MEK/ERK, Akt/mTOR, SRC, and STAT5 pathways. The BCR-ABL tyrosine kinase
      inhibitor imatinib is the standard treatment for CML. However, the development of
      imatinib resistance has become a new challenge for CML treatment. Here, we
      investigated the expression levels of the signaling pathways to explore the cause
      of imatinib resistance and seek new reversing drugs. Our results showed that
      abnormal activation of the BCR-ABL-independent Lyn/ERK signaling pathway was
      involved in imatinib-resistance of K562R cells. Furthermore, p-Lyn and p-ERK were
      up-regulated after treatment with imatinib alone. However, U0126, a MEK1/2
      inhibitor, could counteract the up-regulation induced by imatinib, and the
      combination of imatinib and U0126 could overcome the resistance to imatinib in
      K562R cells. In conclusion, our studies suggest that the combination of imatinib
      and an inhibitor of the ERK signaling pathway may be effective in imatinib
      resistant CML patients.

PMID- 24855826
TI  - A derivative of imidazobenzimidazole, ML106, inhibits melanin synthesis via p38
      MAPK activation.
AB  - We investigated the effects of ML106 on melanogenesis in B16F10 melanoma cells.
      Our results showed that ML106 decreased melanin content and tyrosinase activity
      in a dose-dependent manner. Interestingly, ML106 did not inhibit microphthalmia
      associated transcription factor (MITF) expression, but did decrease tyrosinase
      expression. Thus, we further investigated the expression and degradation of
      tyrosinase and related signal transduction pathways. Although ML106 increased
      glycogen synthase kinase 3beta (GSK3beta) activation, the level of beta-catenin
      level was not affected. Thus, we excluded the involvement of GSK3beta and beta
      catenin in ML106-induced hypopigmentation. However, ML106 induced the
      phosphorylation of p38 mitogen-activated protein kinase (MAPK), causing down
      regulation of tyrosinase. Thus, we next investigated whether tyrosinase down
      regulation was due to proteasomal degradation by p38 MAPK activation. We found
      that ML106-induced tyrosinase down-regulation was restored by MG132, a proteasome
      inhibitor. Thus, we propose that ML106 has hypopigmentary activity through
      tyrosinase degradation via p38 MAPK phosphorylation.

PMID- 24855827
TI  - Anticancer effects of celecoxib through inhibiton of STAT3 phosphorylation and
      AKT phosphorylation in nasopharyngeal carcinoma cell lines.
AB  - Previously, we showed that treatment with celecoxib obviously inhibited
      proliferation of nasopharyngeal carcinoma (NPC) cell lines in a dose-dependent
      manner. However, the underlying molecular mechanisms of its anticancer effect on
      NPC have not been fully clarified. The present in vitro study was performed to
      investigate the mechanisms involved in the anticancer effect of celecoxib in NPC.
      NPC cell line HONE1 was treated with celecoxib at varying concentrations. The
      antiproliferation effect of celecoxib on the HONE1 cell line was assessed with
      methyl thiazolyl tetrazolium (MTT) assay. Western blot analysis of signal
      transducer and activator of transcription 3 (STAT3), phosphorylated STAT3(Y705)
      (pSTAT3(Y705)), Survivin, Mcl-1, Bcl-2 and Cyclin D1 was carried out at various
      concentration of celecoxib for 48 h in HONE1 cell line. Western blot analysis of
      Protein Kinase B (AKT), phosphorylated AKT (pAKT) was performed at increasing
      doses of celecoxib for 48 h in HNE1, CNE1-LMP1 and HONE1 cells. The results
      showed that celecoxib inhibited proliferation of HONE1 cell line in a dose
      dependent manner. Celecoxib inhibited the activation of STAT3 phosphorylation in
      HONE1 cells and the downstream genes of STAT3 (Survivin, Mcl-1, Bcl-2 and Cyclin
      D1) were downregulated after treatment with celecoxib. Furthermore, celecoxib
      could inhibit AKT phosphorylation in HNE1, CNE1-LMP1 and HONE1 cell lines. These
      data suggested that celecoxib was a promising agent for the chemoprevention and
      treatment of NPC.

PMID- 24855828
TI  - Identification of CYP2C19 inhibitors from phytochemicals using the recombinant
      human enzyme model.
AB  - The aim of the present study was to develop the recombinant insect cell-expressed
      protein as an in vitro model for inhibitors screening for human cytochrome P450
      2C19 (CYP2C19), and to use the model to investigate the inhibition effect of
      three phytochemicals on CYP2C19 in vitro. Omeprazole was applied as the probe
      substrate. The estimated inhibitory constant (K(i)) of ticlopidine and
      fluvoxamine were 0.64 +/- 0.025 microM and 0.29 +/- 0.090 microM, respectively.
      After co-incubation with ticlopidine or fluvoxamine, the mean omeprazole
      Michaelis-Menten constant (K(m)) increased from 4.99 +/- 0.22 microM to 16.25 +/-
      1.22 microM or 19.20 +/- 1.73 microM, respectively, while omeprazole's mean
      V(max) did not vary much. Both ticlopidine and fluvoxamine were competitive
      inhibitors of CYP2C19. The IC50 of three phytochemicals, isoalantolactone,
      curcumol and schisandrin A was determined as 38.91 microM, 121.0 microM and 86.41
      microM, and the K(i) as 5.02 +/- 1.04 microM, 35.84 +/- 8.95 microM, and 4.46 +/-
      0.017 microM, respectively. The in vitro model for inhibitor screening
      established using recombinant CYP2C19 could be used to assess the inhibition
      potential of drug candidates. Isoalantolactone and schisandrin A are potent
      inhibitors of CYP2C19, while curcumol is a moderate potent inhibitor of CYP2C19.

PMID- 24855829
TI  - In vivo inhibitory effects of puerarin on selected rat cytochrome P450
      isoenzymes.
AB  - Puerarin, the major bioactive constituent in kudzu root, is used widely in China
      for the treatment of cardiovascular diseases and diabetes. The purpose of this
      study was to find out whether puerarin influences the effect on rat cytochrome
      P450 (CYP) enzymes (CYP2B6, CYP2C9 and CYP3A4) by using cocktail probe drugs in
      vivo. A cocktail solution at a dose of 5 mL/kg, which contained bupropion (20
      mg/kg), tolbutamide (5 mg/kg) and midazolam (20 mg/kg), was given as oral
      administration to rats treated with 10 days oral administration of puerarin.
      Blood samples were collected at a series of time-points and the concentrations of
      probe drugs in plasma were determined by HPLC-MS/MS. The results showed that
      treatment with multiple doses of puerarin had inhibitory effects on rat CYP2B6,
      CYP2C9 and CYP3A4 enzyme activities. Therefore, caution is needed when puerarin
      is co-administered with CYP substrates, in view of herb-drug interactions.

PMID- 24855830
TI  - Regulators of G protein signaling are up-regulated in aspirin-resistant platelets
      from patients with metabolic syndrome.
AB  - G protein-coupled receptor signaling plays a crucial role in platelet function.
      Regulators of G protein signaling (RGSs), which accelerate the deactivation of G
      protein signaling, are expressed in platelets. However, RGS expression has not
      been studied in the context of aspirin resistance. We compared RGS mRNA levels in
      platelets from 39 aspirin-resistant patients and 50 aspirin-sensitive patients
      with metabolic syndrome. Although there were no clinical differences between the
      two groups, transcripts of RGS2, RGS10, and RGS18 were significantly higher in
      aspirin-resistant patients than in aspirin-sensitive patients. This study is the
      first to demonstrate that RGS transcripts are elevated in aspirin-resistant
      platelets from patients with metabolic syndrome.

PMID- 24855831
TI  - Effects of emodin and irbesartan on ventricular fibrosis in Goldblatt
      hypertensive rats.
AB  - Left ventricular (LV) fibrosis is one of the most prominent pathophysiological
      results of hypertension. We initiated this study to investigate the effects and
      mechanisms of emodin and its combination with irbesartan on LV fibrosis in
      Goldblatt (2K1C) hypertensive rats. Goldblatt hypertension rats were prepared by
      two kidney one clip (2K1C) operations and then treated with either emodin,
      irbesartan or their combination. As a result, the systolic blood pressure (SBP)
      and the left ventricular mass index (LVMI) increased significantly (P < or =
      0.05) in all 2K1C rats. After drugs treatment, irbesartan and the drug
      combination remarkably decreased SBP, LVMI, contents of angiotensinII (AngII),
      hydroxyproline and collagen, the mRNA and protein expression levels of matrix
      metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-2 (TIMP-2)
      (P < or = 0.05). As for the emodin, LVMI, contents of hydroxyproline and
      collagen, and MMP-2 and TIMP-2 expression were found to decrease significantly;
      however, the SBP and AngII contents stayed stable within certain extent.
      Therefore, emodin, irbesartan or two drugs together can potentially inhibit the
      ventricular fibrosis in Goldblatt hypertensive rats by reducing MMP-2 and TIMP-2
      expression. Furthermore, the combination of these two drugs may provide a better
      anti-fibrosis effect than the single application.

PMID- 24855833
TI  - Effect of vitamin D supplementation during pregnancy on the Th1/Th2 cell balance
      of rat offspring.
AB  - Vitamin D has important functions in the immune system, and it may suppress the
      proliferation of T helper (Th) cells and modulate their cytokine production. In
      this study, we aimed to investigate the effects of maternal supplementation with
      different doses of vitamin D on the allergy status of the offspring. We gave
      pregnant female rats a low dose (48000IU/kg, equal to 800IU/d in human) and a
      high dose (240000IU/kg,equal to 4000IU/d in human) of vitamin D3 intramuscular
      injection on gestation day (GD)17, and we used an enzyme-linked immunosorbent
      assay (ELISA) to determine the levels of immune responsive cytokines including IL
      4, IgE, and interferon gamma (IFN-gamma) in the offspring. On postnatal day (PND)
      21, plasma IL-4 levels were elevated by 10.43% (p < 0.01) in the offspring from
      the high dose vitamin D3 group compared with the control group. And offspring
      plasma IL-4 levels in the low dose group decreased by 7.27% (p < 0.05) compared
      with the control dose group. We found that the offspring of mothers given a low
      dose of vitamin D3 had a 6.17% (p < 0.01) decrease in their plasma IgE levels
      compared to control animals, but the high dose of vitamin D3 showed no effect.
      The serum 25(OH)D3 levels were negatively correlated with the IL-4 (r = -0.561, p
      < 0.01) and IgE (r = -0.421, p < 0.05) levels of the offspring from the low dose
      group. In the lung tissues of the offspring of the high dose group, we observed
      thickening of the alveolar septa and more inflammatory cells compared with the
      control group and low dose group. Thickened alveolar septa were also found in the
      lung tissues of the offspring from the control group. We conclude that high dose
      vitamin D3 maternal supplementation during pregnancy induced an imbalance of Th1
      and Th2 cells in their offspring resulting allergic and inflammatory response.

PMID- 24855832
TI  - Necrosis factor-alpha (TNF-alpha) response in human hepatoma HepG2 cells treated
      with hepatotoxic agents.
AB  - The liver plays an essential role in xenobiotic metabolism including alcohol and
      drugs. Oxidative stress that usually occurs during the hepatic metabolism
      participates in the pathogenesis of liver disease. Inflammatory cytokines that
      exist in liver in both physiological and pathophysiological conditions may change
      the hepatic toxic response to hepatotoxicants. The human hepatoma cell line HepG2
      is frequently used as in vitro model for biomedical studies. In this work, HepG2
      cells were pre-incubated with or without TNF-alpha, and then treated with
      ethanol, acetaldehyde, acetaminophen and tert-butyl hydroperoxide, respectively.
      Cell viability was measured by MTT assay. The data showed that HepG2 cells were
      generally resistant to xenobiotic compounds, especially to alcohol and
      acetaldehyde, which may be partially caused by the absence of specific cytochrome
      P450 systems in these cells. TNF-alpha could sensitize the toxic response of
      HepG2 cells to those exogenous compounds, indicating the important role of TNF
      alpha in the pathogenesis of alcohol, drugs and oxidant related liver diseases.

PMID- 24855834
TI  - Acorus tatarinowii Schott extract protects PC12 cells from amyloid-beta induced
      neurotoxicity.
AB  - Amyloid-beta induced neurotoxicity has been identified as a major cause of
      Alzheimer's disease. Acorus tatarinowii Schott is one of the most frequently used
      Chinese herbs for Alzheimer's disease treatment. However, the effects of Acorus
      tatarinowii Schott on amyloid-beta mediated nerve cell damage remains unknown. In
      the present study, neuronal differentiated PC12 cells were used as a model to
      evaluate the effects of A. tatarinowii Schott extract (ATSE) against Abeta25-35
      induced neurotoxicity. The results showed pretreatment with ATSE significantly
      protected PC12 cells from Abeta25-35 induced cell death, lactate dehydrogenase
      release, DNA damage, mitochondrial dysfunction and cytochrome c release from
      mitochondria. In addition, pretreatment with ATSE also significantly inhibited
      Abeta25-35 induced caspase-3 activation and reactive oxygen species generation in
      PC12 cells. These observations suggested that ATSE protects PC12 cells from
      amyloid-beta induced neurotoxicity.

PMID- 24855835
TI  - Ergosterol reverses multidrug resistance in SGC7901/Adr cells.
AB  - Multidrug resistance (MDR) is a major obstacle in the chemotherapeutic treatment
      of tumors. Elevated expression of the P-glycoprotein (P-gp) transporter is
      associated with MDR and responsible for the resistance of tumor cells against a
      variety of anticancer drugs. In this study, the reversal effect of ergosterol
      (Erg) on SGC7901/Adr cells was investigated. At concentrations of 1 microM and 5
      microM, Erg could reverse the resistance of SGC7901/Adr to adriamycin up to 4.84
      and 3.92 folds, respectively. Mechanistically, Erg could increase the
      intracellular accumulation of adriamycin and Rh123 in SGC7901/Adr cells through
      inhibiting the transcription of MDR1 gene and down-regulating the expression of P
      gp. In conclusion, Erg could reverse the MDR of SGC7901/Adr cells via its
      influence on P-gp expression and thus be a promising lead compound for future
      studies.

PMID- 24855836
TI  - Mechanical ventilators availability survey in Thai ICUs (ICU-RESOURCE I Study).
AB  - OBJECTIVE: Mechanical ventilators (MV) have been progressing rapidly. New
      ventilator modes and supportive equipments have been developed. However; the MV
      status in Thai ICUs was not available. The objective of this report was to
      describe the MV supply and availability in Thai ICUs and review some important
      characteristics regarding of the availability of MV MATERIAL AND METHOD: The ICU
      RESOURCE I study (Mechanical ventilator part) database was used in the present
      study. Hospital types, MV brands and models were recorded. Statistically
      significant differences between and among groups were defined as p-value < 0.05.
      RESULTS: A total of 2,098 MVs were included in the present study. Of these, 448
      electrically independent MVs (Bird's Mark) were noted (21.35%). The remainder of
      1,650 (78.65%) MVs were electrically dependent MVs (eMV). About 90 percent of
      eMVs were from the following seven eMV brands including Benette, Hamilton, Event,
      Newport, CareFusion or Bird (volume type), Drager and Servo respectively. About
      half of them were from the two brands of Bennette and Hamilton. Recent advanced
      MVs including EvitaXL, Hamilton G5, Servo-I and Epi (NAVA) were more available in
      academic ICUs than in non-academic ICUs. The adult HFOV could be found only in
      academic ICUs in this survey CONCLUSION: Bird Mark ventilators were also a high
      proportion of the MVs in Thai ICUs. Bennette and Hamilton were the most highly
      available MVin this survey. Advanced MV models were more available in academic
      ICUs (Thai Clinical Trial Registry: TCTR-201200005).

PMID- 24855837
TI  - Survey of respiratory support for intensive care patients in 10 tertiary hospital
      of Thailand.
AB  - OBJECTIVE: There are varieties of clinical practices for intensive care
      respiratory support. However there has been no published report characterizing
      its current practice in Thailand. The present study was undertaken to
      characterize the practice of respiratory support for intensive care patients in
      Thai tertiary hospitals. MATERIAL AND METHOD: A cross-sectional survey and
      retrospective historical cohort of intensive care units (ICUs) was performed on
      May 30, 2011 from ten tertiary hospitals in Thailand. The participating ICUs were
      asked to complete the following data of all patients who were mechanically
      ventilated in the ICUs: demographic data, characteristics of respiratory support,
      ICU type, causes of respiratory failure, and weaning technique. RESULTS: A total
      of 258 patients from ten tertiary hospitals were included and analyzed. The
      medical ICU patients remained in the ICU significantly longer than patients in
      other ICUs. Patients in surgical ICUs were significantly younger than patients in
      other ICUs. The prevalence of mechanically ventilated patients in this survey was
      64.7% with a significantly higher proportion in the medical ICUs. The median of
      ventilator days was also significantly higher in the medical ICUs. An invasive
      ventilator was more commonly used in all ICUs rather than non-invasive
      ventilators. The three common causes of respiratory support were severe sepsis or
      septic shock, respiratory failure and post-operation, respectively. Volume
      controlled continuous mandatory ventilation (VC-CMV) ventilation was more
      commonly used as the initial mode of ventilation in both surgical and medical
      ICUs. The maximum plateau pressure was significantly higher in the medical ICU
      patients but there were no differences in maximum tidal volume and PEEP level.
      One-third of the patients were in the weaning process, mostly in the medical
      ICUs. Pressure support was the predominant weaning mode in the medical ICUs,
      while synchronized intermittent mandatory ventilation (SIMV) was more predominant
      in the surgical ICUs. Protocol-based weaning was used in approximately two-thirds
      of patients who were in the weaning process. With repeated estimation equation
      logistic model and left censors cohort to 28 days, the medical ICUs had
      significantly lower ventilator free overtime individual patients when compared
      with surgical ICUs, while there was no difference within mixed ICUs. CONCLUSION:
      The VC-CMV was more commonly used as the initial mode of ventilation in both
      surgical and medical ICUs. Pressure support was the predominant weaning mode in
      the medical ICUs, while SIMV was more predominant in the surgical ICUs.
      Individual patients in medical ICU had a greater number of ventilator days and
      less probability of being ventilator-free.

PMID- 24855838
TI  - Cardiopulmonary monitoring in Thai ICUs (ICU-rESOURCE I Study).
AB  - OBJECTIVE: Cardiopulmonary monitoring (CPM) is rapidly progressing but data
      regarding CPM in Thai ICUs was unavailable. The objective of this study was to
      describe the situation, and gaps of CPM in Thai ICUs. MATERIAL AND METHOD: Data
      were retrieved from the ICU-RESOURCE I study database survey CPM was divided into
      two aspects of device and measurement methods. These were categorized by device
      availability grading (AG), device availability per bed (DPB) and numeric
      frequency grading scale (FGS). Device availability was compared between academic
      and non-academic ICUs. Gap analysis of DPB and FGS was performed. Statistical
      significant difference was defined as p-value < 0.05. RESULTS: One hundred and
      fifty-five ICUs across Thailand participated in this study. Academic ICUs had
      significantly more devices available in new equipment with p < 0.05 (Vigilio,
      PiCCO, NICOM, esophageal pressure monitoring, transcutaneous PO2, electrical
      impedance tomography of lung) as well as measurement methods (stroke volume
      variation [SVV], pulse pressure variation [PPC], central venous oxygen saturation
      [ScvO2], lung mechanics). Most of new and higher technological devices had low
      density and few were available in all of Thai ICUs. However, in gap analysis,
      although these new devices and measurement techniques were available in ICUs,
      they were not frequently utilized. CONCLUSION: New technology devices of CPM had
      more availability in ACAD than in non-ACAD ICUs. Formal continuous training in
      new measurement methods should be established for reducing the availability and
      utilization gap (Thai Clinical Trial Registry: TCTR-201200005).

PMID- 24855839
TI  - Effects of ICU characters, human resources and workload to outcome indicators in
      Thai ICUs: the results of ICU-RESOURCE I study.
AB  - OBJECTIVE: There was a lack of available data regarding intensive care unit (ICU)
      characteristics, human resources, workload, and ICU outcomes in Thai ICUs.
      Therefore, the objectives of the present study were to describe these parameters
      and to demonstrate the association of these predictors to ICU outcome indicators
      including crude mortality, ventilator days and ICU length of stay (ICU-LOS).
      MATERIAL AND METHOD: Retrospective survey to 155 participated ICUs across
      Thailand. ICUs characters, physician and nurse staffing, patient density and ICU
      outcomes indicator at the year 2011 of monthly mortality, ventilator days and ICU
      length of stay were recorded. Multilevel mixed effect linear regression was used
      for cluster analysis. Statistical difference was defined as p-value < 0.05.
      RESULTS: The 132 ICUs (85.16%) were identified as open ICU or low physician
      staffing. The ICUs were directed or consulted by intensivists or critical care
      physicians in 53 ICUs and nearly half of them were located in ICUs at academic
      hospitals. The median value of average daily nurse to patient ratio (NPR) was 0.5
      (Inter-quartile range, IQR 0.23). The median crude mortality was 13.92% (IQR
      10.16). Median ventilator days and ICU-LOS were 5.31 (IQR 4.42) and 5.8 (IQR
      3.0), respectively. A multilevel mixed model demonstrated crude mortality benefit
      in groups of closed ICU management or high physician staffing, academic ICUs,
      regular multidisciplinary round, ICU physician staffing availability and low
      patient density. Although the NPR did not demonstrate any benefit in crude
      mortality, a lower NPR (higher number of nurse staff) was associated with lower
      ventilator days. CONCLUSION: Thai ICUs showed differences in administration
      systems. The outcome indicators of crude mortality, ventilator days and ICU-LOS
      were impacted by the ICU characteristics, human resources and ICU workload (Thai
      Clinical Trial Registry: TCTR-201200005).

PMID- 24855840
TI  - Non-cardiopulmonary monitoring in Thai-ICU (ICU-RESOURCE I study).
AB  - OBJECTIVE: In addition to cardiopulmonary monitoring, non-cardiopulmonary
      monitoring (non-CPM) is considered to be an important parameter in intensive care
      units (ICUs). However no data on this subject has been reported for Thai ICUs.
      The objective of the present study is to describe the non-CPM situation in Thai
      ICUs. MATERIALS AND METHOD: ICU RESOURCE I survey database released during the
      year 2012 was used for the present study. Non-CPMo refers to neurological
      monitoring, renal function monitoring, metabolic monitoring, perfusion monitoring
      and identifying biomarkers. Academic hospital (ACAD), availability grading (AG),
      numeric frequency grading scale (FGS) and device availability per bed (DPB) were
      used for categorization of non-CPM collected data. Significant differences
      between the groups are defined as p < 0.05. RESULTS: Advanced monitoring,
      including; indirect calorimetry, near infrared spectroscopy, peripheral nerve
      stimulation, gut mucosal tonometry and sublingual side stream darkfield imaging
      are currently unavailable in participating Thai ICUs. All ICUs have devices to
      measure the levels of capillary glucose, creatinine kinase MB, troponin T and
      albumin. Bispectral index, ultrasound, continuous renal replacement therapy
      devices, continuous enteral feeding pumps, intra-abdominal pressure monitoring
      devices and rectal temperature measuring devices are available in ACAD facilities
      in greater instances than in other institutions. Similarly; for biomarker and
      drug level monitoring; procalcitonin, interleukin, brain natriuretic peptide,
      total creatinine kinase, neutrophilgelatinase-associated lipocalin (NGAL),
      lactate, central venous oxygen saturation/mixed venous oxygen saturation
      (ScvO2/SvO2), phenytoin, vancomycin and pre-albumin are used more frequently in
      ACADs. Gap analysis demonstrating warmer cabins, NGAL, lactate and ScvO2/SvO2
      show less availability but are frequently used when they have been made
      available. Intra-abdominal pressure and core temperatures are used less in
      general ICU practices and are scarcely found. CONCLUSION: Some of the more
      advanced non-CPM devices are not found in Thai ICUs. Basic non-CPM devices are
      available in all ICUs. Some new devices for measurements and for biomarkers are
      used with greater prevalence in ACAD ICUs. Some measurements including IAP core
      temperature, lactate and ScvO2/SvO) are monitored less frequently in Thai ICUs
      (Thai Clinical Trial Registry: TCTR-201200005).

PMID- 24855841
TI  - Characters of physician and nurse staffing in Thai intensive care units (ICU
      Resource I study).
AB  - OBJECTIVE: There have been no data available on physicians and nurses who are
      vital human resources in Thailand. The objective of this study is to describe
      these characteristics as well as their working patterns in Thai ICUs. MATERIAL
      AND METHOD: Data were retrieved from the ICU RESOURCE I study. Physician and
      nurse characteristics, working patterns and workloads in participating ICUs were
      recorded. After hour consultations, nurse staff years of experience, nurse
      specialist training and patient to bedside nurse ratios (PNR) were collected.
      RESULTS: One hundred and fifty-five hospitals are included in this study.
      Intensivists are available in 53 hospitals with a median of 0-1 intensivist per
      unit. Most intensivists are working in academic ICUs. The two specialties most
      involved in surgical ICUs were in critical care (34.1%) and surgical recovery
      (47.7%). Almost all pediatric ICUs were covered by pediatricians and only a
      quarter of them had been staffed with critical care pediatricians (28.6%). Less
      than 30 percent of Thai ICUs are covered by intensivists. About 42.3% of Thai
      ICUs have no night shift physician and the units contact the attending physicians
      directly. Experienced (more than 5 years) nurses staffing ICUs are at 62.5
      percent. A total of 85.2% of the ICUs have certificated critical care nurses.
      Only 23.2% of all ICUs have an advance practice nurse (APN). The median PNR was
      2.1 with an exception in academic ICUs. CONCLUSION: Intensivists continue to be
      only scarcely available in Thai ICUs. Nurse workloads in non-academic ICUs were
      higher than those in academic ICUs. Specialty training for certified critical
      care nurses is in place for only one-third of the total number of ICU nurses.
      APNs are available in 25% of participating ICUs (Thai Clinical Trial Registry:
      TCTR201200005).

PMID- 24855842
TI  - A multi-center Thai university-based surgical intensive care units study (THAI
      SICU study): methodology and ICU characteristics.
AB  - OBJECTIVE: Although there were two large intra-operative observational studies on
      Thai surgical patients (THAI and THAI-AIMS), there has been no available study on
      critically ill surgical patients regarding their adverse events and outcomes. A
      THAI-Surgical Intensive Care Unit (SICU) study has been established for
      monitoring the occurrence of these adverse events and outcomes in the SICU. The
      objective of this report is to describe the methodology of the THAI-SICU study
      and participating SICUs' characteristics as well as the early recruitment results
      on patients enrolled in the present study. MATERIAL AND METHOD: The present study
      is designed as a multi-center, prospective, observational study. This report
      describes the method of case record form development and summarizes their
      collected parameters as well as the adverse event surveillance variables. All of
      nine SICU characteristics are described regarding their management systems,
      physicians' and nurses' work patterns. The final group of enrolled patients is
      reported. RESULTS: A total of nine university-based SICUs were included in the
      present study. All participating hospitals are residency training centers. Four
      of the SICUs, fulltime directors are anesthesiologists. Only one hospital's SICU
      is directed by a surgeon. Two SICUs were closed ICUs, three were mandatory
      consulting units, one was an elective consultation unit and the remaining three
      ICUs had no directors. Most of the participating SICUs had heterogeneity of
      surgical specialty patients. Six SICUs had regular resident rotations and only
      two of the SICUs had critical care fellowship training. There were significant
      differences regarding the nursing workload among the ICUs. The patient to
      registered nurse ratio ranged from 0.9-2.0. After a total of 19.7 months of a
      recruitment period, the total number of patient admissions was 6,548 (1,894
      patients were excluded). A total cohort of 4,654 patients was included for
      further analytical processes. CONCLUSION: There were differences in ICU
      management systems, physician and specialist coverage, nurse burdens, nurse
      sparing, and types of patients admitted in the university based SICUs. This
      presentation is the pioneer multi-center study on Thai SICUs in which adverse
      events and outcomes are reported.

PMID- 24855843
TI  - Clinical validation of pulse contour and pulse wave transit time-based continuous
      cardiac output analyses in Thai patients undergoing cardiac surgery.
AB  - OBJECTIVE: To evaluate the performance of arterial pressure-based cardiac output
      (APCO) and pulse wave transit time-based cardiac output (esCCO) monitors in Thai
      patients undergoing cardiac surgery with cardiopulmonary bypass. MATERIAL AND
      METHOD: The authors studied fifty Thai surgical patients undergoing coronary
      artery bypass graft surgery (CABG) with cardiopulmonary bypass and requiring
      pulmonary artery catheters and radial artery catheter placement as a standard of
      clinical care. All patients were measured for APCO using the Vigileo/FloTrac and
      esCCO using the esCCO monitoring system. The data were compared to thermodilution
      cardiac output (TDCO) monitoring as a reference method, simultaneously at pre
      induction of anesthesia, post-induction, and every 30 minutes thereafter until
      the completion of the surgery. The bias and precision were assessed using Bland
      Altman analysis. RESULTS: 310 pairs of simultaneous measurements of APCO vs. TDCO
      and 303 pairs of esCCO vs. TDCO were obtained from fifty patients. Both APCO (R =
      0.53, p < 0.0001) and esCCO values (R = 0.56, p < 0.0001) were correlated with
      TDCO values. Either of the changes in APCO (R = 0.63, p < 0.0001) or any changes
      in esCCO (R = 0.60, p < 0.0001) were correlated with changes in TDCO. For APCO
      relative to TDCO, the bias, precision, and the limits of agreement were 0.70, +/-
      1.63, and -2.5 to 3.9 L/min while of esCCO were 1.20, +/-1.59 and -1.9 to 4.3
      L/min, respectively. Comparisons of the bias of APCO and esCCO revealed a level
      of significance of p < 0.001. CONCLUSION: Despite the overestimation of CO
      measurements, APCO and esCCO calibrated with patient information has shown an
      acceptable trend as compared to TDCO in Thai patients undergoing CABG with
      cardiopulmonary bypass. Compared to esCCO, APCO demonstrated no significant
      differences ofprecision however; a lower mean bias was exhibited.

PMID- 24855844
TI  - Incidence and risk factors for ventilator-associated pneumonia in the surgical
      intensive care unit, Siriraj Hospital.
AB  - BACKGROUND: Ventilator-associated pneumonia (VAP) is a serious illness with
      substantial morbidity and mortality resulting in increased costs of hospital
      care. Even though bundles of care to prevent VAP have been established, the
      incidence has not been shown to have improved. OBJECTIVE: To determine the
      incidence and risk factors of VAP in the general surgical intensive care unit,
      Siriraj Hospital (SICU). MATERIAL AND METHOD: During the period from June 1st,
      2010 to June 30th, 2011, 228 adult patients admitted to the general SICU were
      recruited. All patients required ventilator support for more than 48 hours. Data
      were collected by reviewing patient medical records and the retrieval of
      information from the Nosocomial Infection Control, Siriraj Hospital. RESULTS: A
      total of 21 patients (9.21%) were diagnosed with VAP or an incidence of 8.21
      cases/1,000 ventilator days. The onset of VAP was late in the majority of
      patients. The most common pathogens were A. baumannii (66%) followed by P.
      aeuruginosa (19%). Multiple logistic regression analyses showed that the numbers
      of central venous catheter placements, intubations and surgeries and the use of
      muscle relaxants and steroids were independent risk factors for VAP Median
      duration of ventilator and ICU lengths of stay were longer in the VAP group (25
      vs. 6 days, 25 vs. 7 days, respectively; all p < 0.0001). In addition, the
      hospital mortality rates were significantly higher in the VAP group (33.33% vs.
      12.07%; p = 0.008). CONCLUSION: The incidence of VAP was high in the SICU. VAP
      bundles including weaning protocols and airway care should be implemented.

PMID- 24855845
TI  - The impact of intensive care unit admissions following early resuscitation on the
      outcome of patients with severe sepsis and septic shock.
AB  - BACKGROUND: Septic shock is a serious condition associated with a high mortality
      rate. The 'Early goal-directed therapy" has been reported as the effective
      treatment. Whether or not an intensive care unit (ICU) admission can improve the
      outcomes of septic shock patients, has not been elucidated. OBJECTIVE: To
      evaluate the impact of direct ICU admission after initial resuscitation in the
      emergency room (ER) on the outcomes of patients in septic shock. MATERIAL AND
      METHOD: A prospective cohort study including severe sepsis and septic shock
      patients who were admitted from the ER during the period from April 2011 to
      September 2012. The recorded information includes patients' baseline
      characteristics, hemodynamic parameters, and outcomes. The comparisons were
      performed between the ICU versus the non-ICU admission groups. The principal
      outcome was 28-day mortality. RESULTS: Of the 175 enrolled patients, 50 patients
      were directly admitted to the ICU and 125 patients were admitted to a general
      medical ward. The ICU patients were younger (58.6 +/- 19.7 vs. 66.0 ++/- 5.1 year
      old, p = 0.02), had lower mean arterial blood pressures (57.8 +/- 15.3 vs. 66.6
      ++/- 8.4 mmHg, p < 0.001) and presented with a higher proportion of metabolic
      acidosis (60% vs. 33.6%, p = 0.002). In comparison to the non-ICU group, the ICU
      patients received larger volume resuscitation for the first 24 hours (5,694.4 +/-
      2,018.5 vs. 5,004.7 +/- 1,729.7 ml, p = 0.04); had received norepinephrine (88%
      vs. 68%, p = 0.007) and/or dobutamine (20% vs. 4.8%, p = 0.003), and were treated
      for renal replacement therapy (28% vs. 5.6%, p < 0.001) in higher proportions.
      There were trends toward a lower 28 day mortality (18% vs. 25.6%, p = 0.33) among
      the patients in the ICU group. CONCLUSIONS: Apart from the early goal-directed
      therapy, early ICU admission substantially improves the outcomes of septic shock
      patients.

PMID- 24855846
TI  - Mortality correlation factors in patients with lymphoma and acute myeloid
      leukemia admitted into the intensive care unit at a referral center in the south
      of Thailand.
AB  - BACKGROUND: Recent treatments in hematological malignancies have substantially
      improved. Unfortunately, once a patient with a hematological malignancy has
      complications, the prognosis is poor and the in hospital and ICU mortality rates
      are high. Debates concerning the reluctance to admit patients into ICUs with poor
      prognoses often emerge. The aim of the present study is to identify the patients
      who are more likely to benefit from ICU admissions. OBJECTIVES: To assess the
      outcomes and to identify early mortality risk factors in patients with lymphoma
      and acute myeloid leukemia admitted to the Intensive Care Unit (ICU) at
      Songklanagarind Hospital in the south of Thailand. MATERIAL AND METHOD: This is a
      retrospective study of patients diagnosed with lymphoma and acute myeloid
      leukemia admitted to the ICU during the period of January 2004 through May 2008.
      Demographic factors, acute physiology, Acute Physiology and Chronic Health
      Evaluation (APACHE) II scores and variables noted in the first 24-hours were
      collected. The risk factors for deaths in the ICU were studied by univariate and
      multivariate analysis. The risk factors taken from the best multivariate analysis
      model were calculated to predict the probability of lCU mortality. RESULTS: A
      total of 145 patients were studied. The ICU mortality rate was 55.2%. The major
      cause of death was septic shock. Using univariate analysis, the significant
      mortality risk factors were neutropenia, mechanical ventilation, the use of
      vasopressors, abnormal serum creatinine (Cr) and APACHE II scores (p < 0.05).
      Using multivariate analysis, ICU mortality was best predicted on admission by
      mechanical ventilation, the use of vasopressors and the APACHE II scores. The
      presence of neutropenia, mechanical ventilation, vasopressors and an APACHE II
      score of greater than 27 predicts 80% sensitivity and a 75% specificity for an
      82% ICU mortality. CONCLUSION: Patients with lymphoma and acute myeloid leukemia
      admitted into the ICU referral center in the south of Thailand who had mechanical
      ventilation, use of vasopressors and APACHE II scores greater than 27 were
      associated with a higher ICU mortality rate. The authors suggest that early
      identification of the subgroup of patients whose probability of survival is so
      low that advanced ICU support should not be continued would be a more reasonable
      goal. This will allow more efficient care to potential survivors not in this
      group.

PMID- 24855847
TI  - Transthoracic echocardiogram for the diagnosis of right ventricular dysfunction
      in critically ill patients.
AB  - BACKGROUND: Acute right ventricular dysfunction (RVD) is one of the hemodynamic
      alterations in patients with septic shock, pulmonary embolism and ARDS. This
      condition had previously been diagnosed by pulmonary artery catheters (PAC). This
      report is on the use of transthoracic echocardiography (TTE) to diagnose RVD in
      critically ill patients. OBJECTIVE: To evaluate the use of TTE for the diagnosis
      of RVD. MATERIAL AND METHOD: A single center, cohort study, was performed in a 12
      bed medical ICU. All patients who had had PAC insertions during the period from
      August 2009 to October 2010 were included in this study. TTE was performed by an
      investigator (WS. or ST) who was not aware of the patients' diagnoses. The
      hemodynamic parameters were measured within the hour prior to performing a TTE.
      The RVD was diagnosed according to the following criteria: Right atrial (RA)
      pressure > or = 12 mmHg, pulmonary artery occlusion pressure (PAOP) < 18 mmHg,
      mean pulmonary artery pressure (PAP) > 25 mmHg, and pulmonary vascular resistance
      (PVR) > 250 dyne*sec*cm(-5). RESULTS: The PACs were inserted in 59 patients. Of
      these, 15 had been diagnosed with RVD. A total of 83 TTE examinations, in
      comparison with hemodynamic parameters measured from PACs, were studied. The TTE
      parameters; left ventricular (LV) D-shape (sensitivity 61.1%, specificity 84.6%),
      loss of right ventricular (RV) apical triangle (sensitivity 44.4%, specificity
      80%), RV systolic pressure > 40 mmHg (sensitivity 77.8%, specificity 60%) and
      right ventricular end systolic areas: left ventricular end systolic areas
      (RVESA:LVESA) > 0.65 (sensitivity 94.4%, specificity 39.1%) were consistent with
      RVD. The presence of at least 2 out of 4 echocardiograph findings correlated with
      RVD, with the area under the ROC curve at 0.79, with a sensitivity of 77.8% and a
      specificity of 67.7%. CONCLUSION: TTE is an accurate tool for the diagnosis RVD
      in critically ill patients with acceptable sensitivities and specificities.

PMID- 24855848
TI  - Microbiology, risk factors and mortality of patients with intravenous catheter
      related blood stream infections in the surgical intensive care unit: a five-year,
      concurrent, case-controlled study.
AB  - OBJECTIVE: The epidemiologic data of catheter related blood stream infections
      (CRBSI) is different in each type of Intensive Care Unit (ICU). The objectives
      were to identify microbiological patterns, risk factors and mortality analysis in
      the surgical intensive care unit (SICU). MATERIAL AND METHOD: All CRBSI cases
      were reviewed in a 60-months period from the 1st ofJanuary, 2005 through the 31st
      of December, 2009. Two or three control patients, who had been catheterized
      within three days and were free of CRBSI, were randomly selected from the ICU
      admissions registration book as the control group; demographic data, mortality,
      organisms found and antibiotic sensitivity were recorded and analyzed. RESULTS:
      In the 5-years period, 44 patients were diagnosed with a CRBSI and 129 patients
      who were without a CRBSI were selected. The total infection rate was 1.31 per
      1,000 catheter-days. Nine patients who contracted a CRBSI (20.4%) expired. A
      primary diagnosis of gastrointestinal problems had shown the greatest risk for
      developing a CRBSI (69.7%). In proportions of gram negative bacteria:gram
      positive bacteria:fungus, this was measured at 43:36:21 respectively.
      Staphylococcus aureus was the most common gram positive bacteria found.
      Klebsiella pneumoniae, Enterobacter cloacae and Pseudomonas aeruginosa were the
      three most common gram negative bacteria found. The chance of developing a CRBSI
      was significantly increased after 10 days of catheterization. The mortality
      probability of gram negative bacterial infections and fungal infections increased
      over time. This was in contrast to gram positive bacterial infections, which
      decreased over time despite having shown the highest possibility of death earlier
      in catheter days. As for multivariable analyses, catheterization of patients in
      the general wards was the sole independent risk factor of CRBSI occurrences (OR =
      8.67, p < 0.01) and the males (OR = 7.20, p = 0.03) have shown the highest risk
      factors for mortality. CONCLUSION: The occurrence of gram-negative bacteria and
      gram-positive bacteria related CRBSI was similar but the probability patterns of
      increasing the catheter days relating to CRBSI occurrence and mortality rates
      were different. Catheterization in the general wards was the only independent
      risk factor found for contracting a CRBSI in our institute. Males had the highest
      risk for mortality.

PMID- 24855849
TI  - Cost effectiveness analysis of an initial ICU admission as compared to a delayed
      ICU admission in patients with severe sepsis or in septic shock.
AB  - OBJECTIVE: To assess the cost effectiveness of an initial ICU
      admissionforpatients with severe sepsis or those in septic shock following the
      initial resuscitation in the emergency department. MATERIAL AND METHOD: Mortality
      data was generated through retrospective data obtained from 1,048 adult patients
      with severe sepsis or in septic shock from one tertiary care and eight community
      hospitals in Phitsanulok during the period of October 2010 to September 2011.
      These patients were categorized into two groups; as either admitted from the
      emergency department directly to the ICU (stated as an immediate ICU admission)
      or admitted from the emergency department to the general hospital ward due to an
      unavailability of lCU beds (stated as a delayed ICU admission). The overall
      direct costs and characteristics were simulated from a second group of 994 adult
      patients, admitted a year later from selected data by the ICD-10 codes
      [International Classification of Diseases, 10th edition] with the same conditions
      of severe sepsis and septic shock (September 2011 through September 2012), as
      there was no collection of costs and characteristics during the first period
      (October 2010 through September 2011). A decision tree model and an incremental
      cost-effectiveness ratio (ICER) were used for the analyses of the cost
      effectiveness. RESULTS: There were no significant differences in either the mean
      ages or lengths of stay between both groups. All-cause mortality rates have shown
      an incidence of 22.2% for the immediate ICU admission group and an incidence of
      46.3% in the delayed ICUadmission group (odds ratio for the immediate ICU
      admission group was 0. 479 with a 95% confidence interval, 0.376-0.611). Total
      costs (mean, 95% CI) of the immediate ICUadmission group [37,194 baht (32,389
      44,926)] were higher than had been seen in the delayed ICU admission group
      [26,275 (24,300-27,936)]. Incremental cost was 10,919 baht. ICER for the
      immediate ICU admission group was 45,307 baht per life saved. CONCLUSION:
      Immediate ICU admission for patients with severe sepsis or in septic shock
      following the initial resuscitation in the emergency department has shown a
      satisfactory cost-effectiveness profile in low-to-middle income countries.

PMID- 24855850
TI  - Thai-shock survey 2013: survey of shock management in Thailand.
AB  - OBJECTIVE: Pragmatic surveys for shock management by Thai physicians are
      unavailable. The objective of this study is to identify the shock management
      patterns on both; the incidence of septic shock and hemorrhagic shock here in
      Thailand. MATERIAL AND METHOD: Two thousand questionnaires were sent to
      physicians who are called on to care for patients in shock across Thailand. The
      questionnaire is composed of 58 items regarding all aspects of the management of
      septic and hemorrhagic shock. A frequency scale has been defined by 5 levels of
      patient proportion estimates from routine practices. RESULTS: Between April and
      August, 2013, 533 of the distributed questionnaires (26.7%) were returned. In
      severe sepsis and septic shock management, 406 physicians (76.2%) have reported
      the routine use of the quantitative resuscitation protocols. Urine output, mean
      arterial pressures and central venous pressures have been more frequently used
      than central venous oxygen saturation and lactate levels for the resuscitation
      goals. Nearly 80% of these clinicians have shown "often and always" for the
      achievement of the resuscitation goals within 6 hours. Most of the physicians
      (65.3%) had never used procalcitonin biomarkers. Antimicrobial empirical
      treatments were started within 1 hour of admission for 87.7% of these patients
      and were continued for less than 5 days in 67.3% of the cases prior to de
      escalating the treatments. Crystalloids have been the common, initial fluid used
      for resuscitation (98.9% in sepsis, 99.3% in trauma). The most commonly used
      vasopressors are norepinephrine (69.6%) for sepsis and dopamine (63.1%) for
      trauma. The median of the cortisol threshold level for steroid replacement
      therapy is 15 mg/dL, taken from the interquartile range or IQR of 5-19 mg/dL.
      Nearly all the physicians currently use hydrocortisone (96.4%). The median daily
      dose of hydrocortisone is 300 mg (IQR; 200-300). Approximately 50% of the
      physicians prescribed the hydrocortisone in divided doses to be administered
      every 8 hours and 31.8% ordered the medications as a continuous infusion.
      Tapering the dose in reduction varied by 33.6% ofthe physicians over a period of
      2 to 3 days. Central venouspressures (CVP) and fluid challenge tests were more
      frequently used in the evaluation ofpreload rather than some of the newer fluid
      responsiveness methods. Less than 15% of the physicians continued to use
      pulmonary artery catheters in their routine practices. Regarding hemorrhagic and
      traumatic shock, only 162 physicians (39.3%) have been certified in Advance
      Traumatic Life Support (ATLS), but 311 physicians (75.6%) have reported in
      following with the ATLSguidelines. In patients requiring massive transfusions,
      physicians used packed red cells (PRC) and fresh frozen plasma (FFP) in a ratio
      of 1:1 (34.1%). Focus assessment sonography for trauma (FAST) was the most
      commonly used diagnostic method in cases of traumatic shock. CONCLUSION: Most
      physicians manage shock with the current protocols. Hemodynamic goals are
      preferred over tissue perfusion targets. Early antimicrobial therapy and de
      escalation are routinely practiced without the use of infective biomarkers.
      Crystalloids are preferred over colloids for the initial resuscitation. CVPs and
      fluid challenges are still preferred over the new fluid responsiveness methods
      for preload assessment. Hydrocortisone is the most common steroid prescribed for
      septic shock but the threshold of initiation, frequency of use and methods of
      discontinuation vary.

PMID- 24855851
TI  - Do we need to lose more lives unnecessarily? It is time to call for more
      intensivists in Thailand.

PMID- 24855852
TI  - A critical look at critical care medicine in thailand critical care services and
      critical care workforce: the current situation and a future perspective.
AB  - Critical care medicine, one of the newest medical specialties in Thailand, has
      had most of its evolution in the past 25 years. There have been many advances and
      critical care services in major regional hospitals and currently, most university
      medical centers have become state of the art. Critical care fellowship training;
      a subspecialty certification of the primary board of internal medicine,
      anesthesiology, and surgery; has been in place for approximately 14 years.
      Despite the fact that TSCCM is one of the most active societies in education and
      training, the number of qualified intensivists in Thailand is still much less
      than is necessary. In addition, critical care nurses and other related
      professionals necessary for the ICUs' clinical team falls short in delivering
      acceptable, high quality, critical care services. In the very near future,
      Thailand's population will become an increasingly aged society. The movement
      toward one ASEAN community has prompted government policies to encourage Thailand
      to become the Medical Hub of Asia as well as a world-class destination for
      healthcare. Thus, the demand for critical care services will increase
      disproportionally when compared to the training capacity and its popularity as a
      specialty to new medical graduates. A critical look at critical care medicine by
      policymakers and the medical community is a blueprint for preparing and
      optimizing the critical care workforce regarding future planning and the
      development of future policies.

PMID- 24855853
TI  - The role of health information technology on critical care services in Thailand.
AB  - Health information technology (IT) has become an important part of current
      medical practice, especially in critical care services. One significant advance
      is the use of telemedicine which was initiated in Thailand nearly two decades
      ago. Telemedicine is also used in the intensive care unit or what has been termed
      the "Tele-ICU". It has evolved as an alternate paradigm linking the intensivist
      and critical care specialists to critically ill patients in remote areas. In this
      article, the author has reviewed the evidence of health IT on critical care
      services in Thailand, focusing on telemedicine, as well as the concept of the
      'Tele-ICU' and its challenges. These factors may assist intensivists to reach
      more critically ill patients in remote areas.

PMID- 24855854
TI  - The role of the hospitalists in the workforce to address the shortages of
      intensivists in hospitals here in Thailand.
AB  - The problem of a shortage of intensivists in Thailand is increasing annually. As
      stated in The Thai Society of Critical Care Medicine Database, 2013, the number
      of qualified intensivists currently is 163, working in 76 provinces in Thailand.
      This disproportion in the ratio of intensivists has affected patient outcomes. In
      an attempt to solve this problem, there has been an increased number of
      hospitalists working in place of the intensivists. Medical specialties are not
      available in many hospitals of Thailand. Thus, the hospitalists, who care for
      Intensive Care Unit (ICU) patients, are not trained to care for the acutely ill,
      hospitalized patients. Their competencies vary depending on their experience and
      training. In other countries, there has been evidence that properly trained
      hospitalists can work effectively in the ICU. This awareness of the importance of
      intensivists in Thailand is one of the stifling factors; the improvement of the
      hospitalists, determining the hospitalists' workforce and increasing the number
      of the intensivists to match future demands are needed.

PMID- 24855855
TI  - Pitfalls in the management of sepsis in Thailand.
AB  - Septicemia is a major cause of death for patients in the intensive care unit.
      Patient care is not only a function of doctors or nurses but also requires
      teamwork from all healthcare professionals. Starting from the screening of the
      patient in the emergency room, management of these patients includes; early
      antimicrobial therapy, controlling the source of the infection, initiating
      hemodynamic therapy, admitting the patient to the intensive care unit, monitoring
      and surveillance for complications of mechanical ventilation and multiple organ
      failure. Managing all of these require the expertise of multidisciplinary
      physicians. Lack of understanding and knowledge in the management of clinical
      practices can predispose the patient to errors in the treatment of patients here,
      in Thailand. This present guideline is acceptable as an international standard
      and is the current practice of the Faculty of Medicine, Vajira Hospital,
      Navamindradhiraj University. This is an example of the multidisciplinary
      management of septicemia patients in a university hospital in Thailand as set by
      international standards.

PMID- 24855856
TI  - Pitfalls in fluid management for critically ill patients in Thailand.
AB  - Fluid management is one of the most important treatments for critically ill
      patients. It has an influence in patients outcomes and is considered one of the
      most common pitfalls encountered in the management of the critically ill patient.
      In Thailand, fluid overload (> 10% of fluid accumulation), mismanagement of fluid
      restrictions and the "bolusing" of colloid solutions are the main pitfalls that
      may lead to serious complications. These complications can compromise the patient
      in areas such as decreasing the oxygen index, putting the patient in cardiac
      failure and possible acute kidney injury (AKI). They can also increase resource
      utilization and the mortality of critically ill patients. More than 80% of
      critically ill patients, who are admitted to the intensive care units, are
      reimbursed from the "universal coverage". Universal coverage does not support the
      use of albumin solution, which has been reported to improve the function of the
      endothelial glycocalyx layer vascular permeability and improved outcomes in the
      hypoalbuminemic patient (serum albumin < or = 2.5 mg/dL) with severe sepsis, in
      septic shock or undergoing major abdominal surgery. Therefore, primary colloids
      used for resuscitation the patients are 6% hydroxyethyl starch (HES), 4% gelatin
      and fresh frozen plasma. AKI and renal replacement therapy (RRT) continue to be a
      major problem when using these synthetic colloids especially in the high-risk
      patients who receive large amounts of fluids. Evaluation of the fluid
      responsiveness for goal directed therapy is another problem in Thailand. This has
      been predominant in critically ill surgical patients both intra-operatively and
      postoperatively. To obtain optimal benefits of fluid therapy and for the
      prevention of complications associated with this treatment, physician need to
      acquire more knowledge, choose the right strategy, choose the proper type and
      amount of colloid and assure the correct mode of evaluation.

PMID- 24855857
TI  - Pitfalls of mechanical ventilation in Thailand.
AB  - Pitfalls in the respiratory care and mechanical ventilation for patients continue
      to prevail in intensive care unit (ICU) or in some hospital wards in Thailand.
      There are two reasons that explain this phenomenon. Firstly, there are no
      professional respiratory therapists in Thailand. Secondly, most caregivers do not
      possess the adequate knowledge and skills requiredfor respiratory care and for
      initiating, maintaining and weaning patients off mechanical ventilation.
      Physicians and nurses have to practice in respiratory care and mechanical
      ventilation without participating in adequate training during their undergraduate
      studies and postgraduate training. In reality, physicians pay almost no attention
      to respiratory care. They leave the respiratory toilet, ventilator changes and
      monitoring of the patients to nurses who have many other tasks to attend to. To
      solve this problem will require restructuring of the Thai healthcare system. The
      Parliament will need to pass a "Respiratory Therapy Profession Act" to certify
      "respiratory therapists " as a new, registered health profession. The Office of
      the Civil Service Commission has to take the responsibility for creating the job
      title and a job description for respiratory therapists. Academic institutes have
      to provide training courses in respiratory therapy and grant appropriate levels
      of diplomas or certificates in respiratory therapy. Did actics and clinical
      skills required for respiratory care have to be sufficiently integrated into the
      curricula for medical students as well as nursing students. Physicians and nurses
      need to master their skills and acquired appropriate knowledge in respiratory
      care and mechanical ventilation until we can assure the necessary number of
      registered or certified respiratory therapists here in Thailand to help avoid
      such pitfalls.

PMID- 24855858
TI  - Social work practice: innovation and social justice for a changing world.

PMID- 24855860
TI  - Assisting victims of human trafficking: strategies to facilitate identification,
      exit from trafficking, and the restoration of wellness.
AB  - Human trafficking is a pressing social justice concern. Social work is uniquely
      situated to address this problem. However, despite the profession's commitment to
      social justice, the scholarship to equip social workers to address this issue has
      been largely absent from professional discourse. To address this gap, this
      article helps social work practitioners to assist victims of human trafficking.
      After orienting readers to the scope and process of human trafficking, the topics
      of victim identification, exit from trafficking, and the restoration of
      psychological wellness are discussed. By equipping themselves in these three
      areas, practitioners can advance social justice on behalf of some of the most
      exploited people in the world.

PMID- 24855859
TI  - Social work with trauma survivors: collaboration with interpreters.
AB  - Scant attention has been given to the emotional plight, lack of training, and
      stressful working conditions of interpreters serving survivors of severe human
      perpetrated trauma from different parts of the world. This article addresses the
      critical need for effective collaboration between social workers and interpreters
      when the provider and survivor do not speak the same language. The careful
      selection of interpreters; the training, support, and promotion of self-care of
      interpreters; the training needs for social workers related to their work with
      interpreters; and the impact of secondary trauma and organizational support on
      the work of social workers and interpreters are explored. Proposed curriculum
      components for training interpreters and the importance of therapy and ongoing
      supervision for interpreters are highlighted. It is essential to prepare
      interpreters and social workers for the various challenges they will face in
      their collaborative efforts to serve survivors of severe human-perpetrated
      trauma, and organizational support is vital to the success of this work.

PMID- 24855861
TI  - Male victims of intimate partner abuse: use and helpfulness of services.
AB  - Data obtained from a national study of male victims or survivors of intimate
      partner abuse (IPA) indicate that the experience (current or past) of abuse and
      with service use may predict a positive perception toward help seeking. However,
      marital status and a tendency to minimize problems may predict negative attitudes
      toward help seeking. Empirical evidence from this mixed-method study suggests
      that male victims face many interpersonal and societal obstacles. Feeling
      uncomfortable when requesting assistance, men in IPA situations are affected by a
      masking factor that causes them to hide their situation and contributes to a
      misconception factor that causes people to treat men as the sole perpetrator.
      Although men are eligible, services may not be perceived as being available or
      helpful. The study yields important implications for social work practice, and
      the findings result in several recommendations for increased awareness about IPA,
      advocacy for gender-inclusive services, revision of laws and policies, increased
      research, and emphasis on funded and anonymous services.

PMID- 24855862
TI  - An update to "among the missing: lesbian and gay content in social work
      journals".
AB  - The needs of lesbians and gay men appear to be minimally represented in social
      work literature. This study applied content analysis to four major social work
      journals published between 1998 and 2012, and it served to update the work of Van
      Voorhis and Wagner that examined content in the same four journals between 1988
      and 1997. Of the 2,335 articles published in Child Welfare, Families in Society,
      Social Service Review, and Social Work during the 15-year period, 55 met the
      criteria for inclusion. Results reflect a significant decrease in the quantity of
      articles when compared with the previous report, with the largest decrease
      noticed in articles that addressed HIV/AIDS. The need to expand the type and
      amount of content related to this population continues.

PMID- 24855863
TI  - Designing a group therapy program for coping with childhood weight bias.
AB  - Research indicates that the negative psychosocial consequences of childhood
      obesity may reflect the degree of weight bias and mistreatment affecting the
      child. Even though comprehensive practice models evolve over time, the intense
      distress of these children calls for more timely intervention. Using a
      modification of social research and development methodology, a short-term group
      therapy approach using cognitive and behavioral methods was designed.
      Questionnaires were developed to assess both the child's and the parents'
      perceptions of the frequency, circumstances, and responses to being teased. At
      the end of the program, all of the children and parents showed proficiency in
      describing and demonstrating the coping strategies in the curriculum. A two-year
      follow-up found that most of the children reported fewer episodes of teasing.
      This article demonstrates the use of intervention research methodology to rapidly
      design and implement a preliminary approach to help children with severe obesity
      cope with weight-related teasing. Although this program needs further empirical
      testing and refinement before it can be more widely deployed, it represents an
      important initiative in responding to the distress of children who are victimized
      because of obesity.

PMID- 24855864
TI  - Communities respond to predatory lending.
AB  - Low-income communities in the United States have faced a history of financial
      marginalization and exploitation, most evident today in the proliferation of
      predatory financial services, such as payday lending and check-cashing services.
      Ameliorating the negative effects of predatory lending has become increasingly
      important on the agenda of community development efforts and the field of social
      work. Through the use of case studies, this article describes three specific
      strategies that communities use to increase financial inclusion and buffer
      against the deleterious effects of predatory lending: inclusion, community-based
      alternatives, and community advocacy.

PMID- 24855865
TI  - Economic insecurity and access to the social safety net among Latino farmworker
      families.
AB  - Farmworkers experience pervasive economic insecurity in part because of the
      seasonal nature of agricultural work and limited employment protections. Yet
      little is known about the adequacy of the social safety net in responding to
      farmworker needs. Using data from the 2005-2009 National Agricultural Workers
      Survey (N = 10,469), the current study analyzed predictors of social welfare
      participation among Latinos, who represent approximately 80 percent of all
      farmworkers. Nearly 95 percent are immigrants, although almost half of them have
      lived in the United States for more than 10 years. Descriptive analyses showed
      that, even among farmworker households whose income fell below the poverty line
      or that were headed by legally documented individuals, social services use was
      very low. Logistic regression analyses revealed that degree of social integration
      influenced social welfare participation, controlling for education, poverty
      status, family composition, and employment characteristics. Latino farmworkers
      who were recent immigrants (that is, in the United States for less than five
      years) had significantly lower odds of access to social insurance and public
      assistance programs relative to their U.S.-born counterparts. Low self-reported
      English ability significantly decreased access to most social insurance programs
      but not public assistance receipt. The findings indicate the need for social
      workers to engage in outreach efforts and policy advocacy to improve farmworkers
      access to social welfare.

PMID- 24855866
TI  - Exiling children, creating orphans: when immigration policies hurt citizens.
AB  - Citizen-children born in the United States to undocumented immigrants have become
      collateral damage of immigration enforcement. These children suffer the effects
      of immigration laws designed to deport large numbers of people. In removal
      proceedings, parents often must decide to either leave their citizen-children
      behind in the care of others or take them to a country the child may have never
      known. Accordingly, immigration policy frequently creates two de facto classes of
      children: exiles and orphans. In discussing these classes, the authors offer a
      summary of how U.S. citizen-children come into contact with the immigration
      enforcement system. The article explores the impact of detention and deportation
      on the health, mental health, and developmental trajectories of citizen-children
      and argues for reforms in policy and practice that will adhere to the highest
      standards of child welfare practice. By integrating these children into the
      immigration discourse, practitioners and policymakers will be better able to
      understand the effects of immigration enforcement, reduce harm to children, and
      provide for the protection of their rights.

PMID- 24855867
TI  - Social work and collegiate recovery programs.

PMID- 24855869
TI  - Signs of sociolinguistic misunderstanding: the case of a boy named HUNTER.

PMID- 24855868
TI  - Exploring the ethical dilemma of integrating social work values and military
      social work practice.

PMID- 24855870
TI  - The organizational revolution and the human sciences.

PMID- 24855871
TI  - A scholarly intermediary between the Ottoman Empire and Renaissance Europe.
AB  - This essay studies Moses Galeano, a Jewish scholar with ties to Crete and the
      Ottoman Sultan's court, who traveled to the Veneto around 1500. After describing
      Galeano's intellectual milieu, it focuses, first, on circumstantial evidence that
      he transmitted information central to the rise of Renaissance astronomy. Galeano
      knew of theories that strongly resemble portions of astronomy texts written by
      Giovanni Battista Amico and Girolamo Fracastoro at Padua a few decades later. He
      also knew about theories pioneered by the Damascene Ibn al-Shatir (d. 1375) that
      strongly resemble portions of Copernicus's work. Next, the article turns to
      concrete evidence showing that Galeano was part of a network of Jewish scholars
      who did have contact with Christian scholars in Europe. The essay concludes that,
      while it is impossible to prove that Galeano had direct contact with Copernicus,
      he most likely had contact with some European astronomer(s) in the Veneto.

PMID- 24855872
TI  - Making expert knowledge through the image: connections between antiquarian and
      early modern scientific illustration.
AB  - This essay examines drawings of antiquities in the context of the history of
      early modern scientific illustration. The role of illustrations in the
      establishment of archaeology as a discipline is assessed, and the emergence of a
      graphic style for representing artifacts is shown to be closely connected to the
      development of scientific illustration in the seventeenth and early eighteenth
      centuries. The essay argues that the production of conventionalized drawings of
      antiquities during this period represents a fundamental shift in the approach to
      ancient material culture, signifying the recognition of objects as evidence. As
      has been demonstrated in other scientific fields, the creation of a visual system
      for recording objects was central to the acceptance of artifacts as "data" that
      could be organized into groups, classified as types, and analyzed to gain
      knowledge of the past.

PMID- 24855873
TI  - Neuroscience, neurohistory, and the history of science: a tale of two brain
      images.
AB  - This essay introduces a Focus section on "Neurohistory and History of Science" by
      distinguishing images of the brain as governor and as transducer: the former
      treat the brain as the executive control center of the body, the latter as an
      interface between the organism and reality at large. Most of the consternation
      expressed in the symposium about the advent of neurohistory derives from the
      brain-as-governor conception, which is rooted in a "biologistic" understanding of
      humanity that in recent years has become bound up in various nefarious
      "neoliberal" political and economic agendas. However, given the sophisticated
      attitude that neurohistory's leading champion, Daniel Smail, displays toward
      evolutionary theory's potential impact on historical practice, he is perhaps
      better understood as part of the brain-as-transducer tradition. This tradition,
      largely suppressed in current representations of neuroscience, has a strong
      theological provenance, ultimately concerned with our becoming attuned to the
      divine frequency, not least by extending the powers of the human nervous system
      through technology. This essay sympathetically explores the implications of this
      perspective for historical practice.

PMID- 24855874
TI  - Neurohistory in action: hoarding and the human past.
AB  - A neurohistorical approach begins with the principle that the human brain is
      relatively plastic and therefore continuously open to developmental and cultural
      influences. This does not mean that we should treat the brain as a blank slate.
      Instead, such influences, as they interact with given brain/body systems, can
      generate unpredictable forward-acting effects. The phenomenon of compulsive
      hoarding offers a case study of a historically or culturally situated behavior
      that can be approached in this way. Hoarding appears to be correlated with
      cognitive lesions or genetic predispositions. Yet although the behavior is very
      visible today, there is little evidence for the practice in the human past,
      suggesting that something has triggered the growing prevalence of the phenomenon.
      Using the coevolutionary approach intrinsic to environmental history, we can
      treat the rise of compulsive hoarding as an emergent phenomenon generated by the
      unpredictable ways in which cognitive and endocrinological systems have
      interacted with a changing material environment. The results of this inquiry
      suggest not only why history needs cognitive neuroscience but also why
      neuroscience needs history.

PMID- 24855875
TI  - History and neuroscience: an integrative legacy.
AB  - The attitudes that characterize the contemporary "neuro-turn" were strikingly
      commonplace as part of the self-fashioning of social identity in the biographies
      and personal papers of past neurologists and neuroscientists. Indeed, one
      fundamental connection between nineteenth- and twentieth-century neurology and
      contemporary neuroscience appears to be the value that workers in both domains
      attach to the idea of integration, a vision of neural science and medicine that
      connected reductionist science to broader inquiries about the mind, brain, and
      human nature and in so doing supposedly resolved once and for all questions
      germane to the human sciences, humanities, and arts. How those attitudes were
      produced and reproduced first in neurology and then in neuroscience; in what way
      they were constructed and disciplined, thereby eventuating in the contested
      sciences and medicines of the mind, brain, and nervous system; and even how they
      garnered ever-wider contemporary purchase in cultures and societies are thus
      fascinating problems for historians of science and medicine. Such problems shed
      light on ethics, practices, controversies, and the uneasy social relations within
      those scientific and medical domains. But more to the point of this essay: they
      also account for the apparent epistemological weight now accorded "the neuro" in
      our contemporary moment. They thus illuminate in a rather different way why
      historians have suddenly discovered the value of "the neuro".

PMID- 24855876
TI  - Neurohistory is bunk? The not-so-deep history of the postclassical mind.
AB  - The proliferation of late of disciplines beginning in "neuro"--neuroeconomics,
      neuroaesthetics, neuro-literary criticism, and so on--while welcomed in some
      quarters, has drawn a great deal of critical commentary as well. It is perhaps
      natural that scholars in the humanities, especially, tend to find these "neuro"
      prefixes irritating. But by no means all of them: there are those humanists
      (evidently) who discern in this trend a healthy development that has the
      potential of "revitalizing" the notoriously bookish humanities. Neurohistory (or
      "deep" history) is a case in point, typically being dismissed (if registered at
      all) by historians while finding more sympathetic consideration elsewhere. While
      it sides with the former position, this essay attempts to develop a more complex
      picture. It will suggest that defiant humanists may underestimate the extent to
      which they are already participating in a culture profoundly tuned toward a quasi
      naturalistic construction of the mind/brain as an embodied, situated, and
      distributed thing. The roots of this construction will be traced into the
      popular, academic, and technological discourses that began to surround the "user"
      in the 1980s, with special emphasis on the concomitant assault on "cognitivism."
      What is more, the very same story--insofar as it demonstrates the complicity of
      the "postclassical" mind with our own man-made and "digital" age--will serve to
      complicate the neuro-optimists' vision of human nature exposed by a new kind of
      science.

PMID- 24855877
TI  - Neural veils and the will to historical critique: why historians of science need
      to take the neuro-turn seriously.
AB  - Taking the neuro-turn is like becoming the victim of mind parasites. It's
      unwilled (although there are those who will it at a superficial level for various
      strategic reasons). You can't see mind parasites; they make you think things
      without allowing you to know why you think them. Indeed, they generate the
      cognitive inability to be other than delighted with the circumstances of your
      affected cognition. It's not as if you can take off your thinking cap and shoo
      the pests away. You can't see them--or even know that you could want to. You
      can't stand on the outside looking in at your cognitive processes. But
      historically speaking, you are also inside a (broadly postmodern) culture and
      (broadly neoliberal) socioeconomic order that places the legitimacy of the neuro
      beyond critique. And the neuro-turn does more: it delegitimizes critique itself,
      at least as we have known it since Marx. This essay briefly explores how we got
      here, what the "here" is, and what its implications are for historical critique.

PMID- 24855878
TI  - Eloge: Charles Weiner (1931-2012).

PMID- 24855879
TI  - Eloge: Erwin Hiebert.

PMID- 24855880
TI  - Drug taking beliefs of Australian adolescents: a pilot study.
AB  - In this study adolescents offered their insights and perspectives of factors
      associated with adolescent illicit drug taking intentions. The factors explored
      were identified using a cross-disciplinary approach involving the Theory of
      Planned Behavior (TPB) and criminological theories, and these formed the
      framework for data analysis. Interviews with 24 students aged 15-17 found that
      adolescents' beliefs to drug taking attitudes, subjective norms, perceived
      behavioral control, moral norms, negative affect, and reputation enhancement
      involved a number a sub-themes that provided an in-depth understanding of the
      association of these components to intended drug use. The incorporation of these
      elements in drug education programs could be an effective approach in prevention
      interventions for adolescent drug use.

PMID- 24855881
TI  - Predictive models of alcohol use based on attitudes and individual values.
AB  - Two predictive models are developed in this article: the first is designed to
      predict people's attitudes to alcoholic drinks, while the second sets out to
      predict the use of alcohol in relation to selected individual values. University
      students (N = 1,500) were recruited through stratified sampling based on sex and
      academic discipline. The questionnaire used obtained information on participants'
      alcohol use, attitudes and personal values. The results show that the attitudes
      model correctly classifies 76.3% of cases. Likewise, the model for level of
      alcohol use correctly classifies 82% of cases. According to our results, we can
      conclude that there are a series of individual values that influence drinking and
      attitudes to alcohol use, which therefore provides us with a potentially powerful
      instrument for developing preventive intervention programs.

PMID- 24855882
TI  - Navigating local smoke-free multi-unit housing policy adoption.
AB  - California state-funded local tobacco control projects have instituted smoke-free
      multi-unit housing (MUH) policy adoption campaigns in order to secure voluntary
      policy throughout the state. While landlords can legally prohibit smoking at MUH
      complexes in California, they often oppose such measures. The objective of this
      study was to analyze voluntary smoke-free policy campaigns of state-funded local
      projects by focusing on the challenges they faced. Specifically, we examined 40
      local campaigns in California led by county health departments and community
      based organizations, focusing on the barriers the local projects often had to
      overcome to enact policy. Our results identify arguments and issues typically
      raised by MUH property landlords, including the notion of tenant smoker and
      privacy rights, potential negative effects of smoke-free policy, and issues
      concerning the enforcement of policy. Moreover, relationships between local
      project personnel and MUH management often soured, which sometimes derailed smoke
      free policy campaigns altogether. Our findings provide agencies with insights
      from the MUH property landlord perspective that will serve to inform future
      campaign strategy.

PMID- 24855883
TI  - An evaluation of the 4-H Health Rocks program: implications for program
      improvement.
AB  - The National 4-H Council developed the Health Rocks substance abuse educational
      program to prevent youth from engaging in risky behaviors. The program was
      presented in 2010 to more than 8,000 middle school youth in Georgia. A post-then
      pre evaluation was conducted with youth who completed 10 hours of instruction to
      determine if changes in youth knowledge, beliefs/attitudes, skills, and
      behavioral intentions occurred during the course of the program. This study
      sought to measure the impact of the program and critically evaluate the
      questionnaire used. The data revealed statistically significant increases in
      knowledge, beliefs/attitudes, skills, and behavioral intentions of participating
      youth. Suggestions for improvement of the questionnaire included utilizing
      questions that are more specific to the curriculum and adding questions to
      measure the influence of peer pressure.

PMID- 24855884
TI  - Perceived role legitimacy and role importance of Australian school staff in
      addressing student cannabis use.
AB  - The high prevalence of cannabis use by Australian secondary school students makes
      schools an ideal setting for the delivery of substance use prevention programs.
      Although efficacious school-based cannabis prevention programs exist, there is
      scant research investigating the perceived role legitimacy and role importance of
      school staff. As such, this study surveyed a sample of 1691 Australian school
      staff by utilizing Generation Next seminars which are attended by professionals
      working with young people. The self-completed survey identified that, despite
      elevated contact with students relative to other school staff, teachers reported
      the least role importance and legitimacy of all school staff. Further, teachers
      reported the lowest level of staff drug education training, which was an
      important predictor of an increased feeling of role importance and legitimacy
      among school staff.

PMID- 24855885
TI  - Can personality account for differences in drinking between college athletes and
      non-athletes? Explaining the role of sensation seeking, risk-taking, and
      impulsivity.
AB  - Collegiate athletes are an at-risk population for high risk drinking and related
      consequences when compared to the general college student population. However,
      little is known about how aspects of an individual's personality contribute to
      this relationship, making intervention efforts challenging. The current study
      examined sensation seeking, risk-taking, and impulsivity as methods of explaining
      the relationship between athlete and non-athlete drinking behaviors. Findings
      suggested athletes drank significantly more than non-athletes and this
      relationship seemed to function through sensation seeking and risk-taking. The
      role these characteristics play as risk or protective factors for high risk
      drinking and implications for interventions prioritizing athletes are discussed.

PMID- 24855886
TI  - The role of psychological factors in bipolar disorder: prospective relationships
      between cognitive style, coping style and symptom expression.
AB  - OBJECTIVE: Psychological factors contribute to bipolar disorder illness course,
      representing targets for psychological intervention. Research to date has focused
      on bipolar I disorder, extrapolating results to bipolar II disorder. The current
      study addresses this discrepancy by exploring cognitive and coping styles in
      patients diagnosed with bipolar I or II disorder. METHODS: Participants were
      recruited from the Sydney-based Black Dog Institute. Diagnoses were derived via
      the MINI International Neuropsychiatric Interview. Baseline cognitive and coping
      style measures were completed, and mood symptoms assessed over a 6-month period.
      Clinician-rated mood status was assessed at follow-up to determine the predictive
      utility of cognitive and coping styles. RESULTS: The follow-up sample comprised
      151 participants. Differential relationships between cognitive style, coping
      styles and mood symptoms emerged across the bipolar sub-types. Some key
      differences were that a broader set of negative cognitive styles were associated
      with bipolar II depression symptoms; while few relationships were observed
      between coping styles and bipolar II symptoms. CONCLUSION: Differences in
      cognitive and coping style relationships with symptom expression across bipolar I
      and II disorder may provide clinicians with fruitful guides for directing
      treatment interventions when relevant maladaptive styles are observed. Further
      exploration of differences in cognitive and coping styles in bipolar I and II
      disorder is warranted.

PMID- 24855887
TI  - Methylphenidate treatment causes oxidative stress and alters energetic metabolism
      in an animal model of attention-deficit hyperactivity disorder.
AB  - OBJECTIVES: To evaluate oxidative damage through the thiobarbituric acid-reactive
      species (TBARS) and protein carbonyl groups; antioxidant enzymatic system -
      superoxide dismutase (SOD) and catalase (CAT); and energetic metabolism in the
      brain of spontaneously hypertensive adult rats (SHR) after both acute and chronic
      treatment with methylphenidate hydrochloride (MPH). METHODS: Adult (60 days old)
      SHRs were treated during 28 days (chronic treatment), or 1 day (acute treatment).
      The rats received one i.p. injection per day of either saline or MPH (2 mg/kg).
      Two hours after the last injection, oxidative damage parameters and energetic
      metabolism in the cerebellum, prefrontal cortex, hippocampus, striatum and cortex
      were evaluated. RESULTS: We observed that both acute and/or chronic treatment
      increased TBARS and carbonyl groups, and decreased SOD and CAT activities in many
      of the brain structures evaluated. Regarding the energetic metabolism evaluation,
      the acute and chronic treatment altered the energetic metabolism in many of the
      brain structures evaluated. CONCLUSION: We observed that both acute and chronic
      use of methylphenidate hydrochloride (MPH) in adult spontaneously hypertensive
      rats (SHRs) was associated with increased oxidative stress and energetic
      metabolism alterations. These data also reinforce the importance of the SHR
      animal model in further studies regarding MPH.

PMID- 24855888
TI  - 8-pCPT, an Epac activator, impairs conditioned place preference based on nucleus
      accumbens amphetamine in rats.
AB  - OBJECTIVES: Dopamine receptor-mediated 3',5'-cyclic adenosine monophosphate
      (cAMP)-dependent intracellular signalling is important for reward-related
      learning. cAMP activates cAMP-dependent protein kinase (PKA) and exchange protein
      directly activated by cAMP (Epac). We tested the hypothesis that reward-related
      learning may be mediated by Epac. METHODS: We evaluated conditioned place
      preference (CPP) on the basis of nucleus accumbens (NAc) injections of
      amphetamine (20 MUg/0.5 MUl/side) plus Sp-adenosine 3',5'-cyclic
      monophosphorothioate triethylamanine (Sp-cAMPS) (0.1, 1.0, 10, 15, 20 MUg/0.5
      MUl/side), an activator of both PKA and Epac, or amphetamine (20 MUg) plus 8-(4
      chlorophenylthio)-2'-O-methyladenosine-3',5'-cyclic monophosphate (8-pCPT) (0.73,
      1.27, 1.45, 2.89, 5.78, 11.56 MUg/0.5 MUl/side), an activator of Epac. RESULTS:
      In agreement with previous results, Sp-cAMPS dose-dependently impaired CPP. 8
      pCPT impaired CPP at one dose (1.45 MUg/0.5 MUl/side) and we replicated this
      effect three times. CONCLUSION: The results implicate Epac in the acquisition of
      reward-related learning.

PMID- 24855889
TI  - Evaluation of antidepressant and memory-improving efficacy of aripiprazole and
      fluoxetine in alcohol-preferring rats.
AB  - INTRODUCTION AND AIMS: Dependence on ethanol increases the risk of depression in
      patients and leads to a damage and deficiencies of brain function, which manifest
      in cognitive functions impairment. Aripiprazole (ARI) is an atypical
      antipsychotic drug, which has also been shown to have a beneficial effect on
      cognitive function. Results of many studies show that, for ARI's antidepressant
      effect to manifest itself, it is necessary to use a combined therapy with a drug
      from the group of selective serotonin reuptake inhibitors (SSRIs). The aim of
      this paper was to assess the antidepressant and impact of ARI on spatial memory
      in alcohol-preferring rats (EtNPRs). DESIGN AND METHODS: In our study, we used
      Porsolt's forced swimming test (antidepressant effect) and Morris water maze
      test. The tests have been conducted upon administration of ARI (6 mg/kg i.p.),
      fluoxetine (FLX; 5 mg/kg p.o.) and combined administration of both drugs in
      alcohol-dependent rats. RESULTS: The results of behavioural tests carried out
      have shown a lack of antidepressant and procognitive effects of either ARI or FLX
      in EtPRs after acute and chronic treatment. Combined administration of both drugs
      would lead to spatial memory deterioration in the study animals. DISCUSSION AND
      CONCLUSIONS: Our results suggest that ARI applied in the experiment had no
      antidepressant effect and failed to improve spatial memory in study rats.
      Potential antidepressant and procognitive properties of this drug resulting from
      its mechanism of action encourage attempts (design) of further research aimed at
      developing a dose, which will show such effects in alcohol-preferring animals.

PMID- 24855890
TI  - Are oxidative stress markers useful to distinguish schizoaffective disorder from
      schizophrenia and bipolar disorder?
AB  - OBJECTIVE: Schizoaffective disorder is a disease with both affective and
      psychotic symptoms. In this study, we aimed to compare oxidative metabolism
      markers of schizoaffective disorder, bipolar disorder and schizophrenic patients.
      Furthermore, we also aimed to investigate whether schizoaffective disorder could
      be differentiated from schizophrenia and bipolar disorder in terms of oxidative
      metabolism. METHODS: Total oxidant status (TOS) and total antioxidant status
      (TAS) were measured in the blood samples that were collected from schizoaffective
      patients (n = 30), bipolar disorder patients (n = 30) and schizophrenic patients
      (n = 30). Oxidative stress index (OSI) was calculated by dividing TOS by TAS.
      RESULTS: TOS and OSI were found to be higher in patients with schizoaffective
      disorder compared with those in schizophrenia and bipolar disorder patients. TAS
      was not significantly different between the groups. CONCLUSION: Schizoaffective
      disorder was found to be different from bipolar disorder and schizophrenia in
      terms of oxidative parameters. This result may indicate that schizoaffective
      disorder could differ from bipolar disorder and schizophrenia in terms of
      biochemical parameters. Increased TOS levels observed in schizoaffective disorder
      may suggest poor clinical course and may be an indicator of poor prognosis.

PMID- 24855891
TI  - Treatment with citalopram, but not with agomelatine, adversely affects sperm
      parameters: a case report and translational review.
AB  - BACKGROUND: Adverse effects of antidepressant drug treatmenton sexual function
      are well documented but the effects of antidepressants on sperm production have
      not been researched extensively. METHODS: A narrative of an interventional case
      report of sperm parameters in a 30-year-old Caucasian man with a diagnosis of
      mixed depressive and anxiety disorder, who underwent citalopram treatment,
      followed by agomelatine treatment. Clinical observations prompted a review of the
      pre-clinical and clinical literature on the effects of antidepressant
      administration or treatment on sperm production and parameters. Findings from the
      review are discussed to suggest potential underlying mechanisms. RESULTS:
      Abnormal sperm parameters were associated with treatment with the SSRI
      citalopram. There was an improvement in sperm concentration, motility,
      progressive motility and sperm morphology following its withdrawal. There was no
      similar association during subsequent treatment with agomelatine. The clinical
      observations reflect findings from animal studies, which indicate that
      antidepressants can have untoward effects on spermatogenesis. CONCLUSIONS: SSRI
      treatment can be associated with impaired semen quality. Potential underlying
      mechanisms include changes in sperm DNA integrity, activation of IDO and shifting
      tryptophan metabolism. Further studies of the effects of antidepressants on
      spermatogenesis might benefit from including investigation of changes in IDO
      activity during antidepressant administration.

PMID- 24855896
TI  - Copper-mediated tandem oxidative C(sp2)-H/C(sp)-H alkynylation and annulation of
      arenes with terminal alkynes.
AB  - The copper-mediated tandem oxidative C(sp(2))-H/C(sp)-H cross-coupling and
      intramolecular annulation of arenes with terminal alkynes has been developed,
      which offers a highly efficient approach to the 3-methyleneisoindolin-1-one
      scaffold. In this oxidative coupling process, Cu(OAc)2 acts as both the promoter
      and the terminal oxidant. This protocol features a wide substrate scope; high
      functional group tolerance; exclusive chemo-, regio-, and stereoselectivity; and
      simple, easily available, and inexpensive reaction system. The transformation has
      demonstrated for the first time that Cu(OAc)2 can be renewable after undergoing
      an oxidative reaction. 

PMID- 24855894
TI  - Protein-ligand docking using hamiltonian replica exchange simulations with soft
      core potentials.
AB  - Molecular dynamics (MD) simulations in explicit solvent allow studying receptor
      ligand binding processes including full flexibility of the binding partners and
      an explicit inclusion of solvation effects. However, in MD simulations, the
      search for an optimal ligand-receptor complex geometry is frequently trapped in
      locally stable non-native binding geometries. A Hamiltonian replica-exchange (H
      REMD)-based protocol has been designed to enhance the sampling of putative ligand
      receptor complexes. It is based on softening nonbonded ligand-receptor
      interactions along the replicas and one reference replica under the control of
      the original force field. The efficiency of the method has been evaluated on two
      receptor-ligand systems and one protein-peptide complex. Starting from misplaced
      initial docking geometries, the H-REMD method reached in each case the known
      binding geometry significantly faster than a standard MD simulation. The approach
      could also be useful to identify and evaluate alternative binding geometries in a
      given binding region with small relative differences in binding free energy. 

PMID- 24855897
TI  - [Sugery in elderly people: can we get better results?].

PMID- 24855898
TI  - [Considerations about Lofgren syndrome].

PMID- 24855900
TI  - [Hypertension guidelines: too many and discordant].

PMID- 24855899
TI  - [Lofgren syndrome: a study of 80 cases].
AB  - BACKGROUND AND OBJECTIVE: Lofgren's syndrome is characterized by hiliar
      adenopathies, erythema nodosum and arthritis. It is a benign variant of
      sarcoidosis, common in the Mediterranean area. To describe the clinical
      characteristics, treatment and outcome of a series of patients diagnosed with
      Lofgren's syndrome. PATIENTS AND METHODS: Retrospective design (1984-2013).
      SETTING: Two university hospitals with a reference population of 1,015,000
      inhabitants. RESULTS: Eighty patients were diagnosed: 29 men and 51 women (mean
      age 42.3 years). Forty eight patients (60%) presented with the classical triad:
      hiliar adenopathies, erythema nodosum and arthritis; 18 (22%) with hiliar
      adenopathy and arthritis; 13 (16%) hiliar adenopathies and erythema nodosum. All
      showed abnormalities in the chest study. According to the radiological pattern,
      patients were classified in stage i-ii. Biopsy was performed in 39 patients and
      was diagnostic in 28. Treatment was based on non-steroidal anti-inflammatory
      drugs (54 patients, 67%) and corticosteroids (33 patients, 41%). Fourteen
      patients (17%) suffered a recurrence of the disease. CONCLUSIONS: Lofgren's
      syndrome is a benign form of sarcoidosis with a well defined clinical pattern.
      Biopsy is usually not required. Recurrence is scarce. The disease has a good
      prognosis.

PMID- 24855901
TI  - [Job profile diagram and working aptitude. Occupational Medicine].

PMID- 24855902
TI  - [Reply].

PMID- 24855903
TI  - Investigational epigenetically targeted drugs in early phase trials for the
      treatment of haematological malignancies.
AB  - INTRODUCTION: For decades, cancer research has focussed on the genetic defects
      that drive tumourigenesis. However, recent high-resolution sequencing studies
      have uncovered mounting evidence for the complementary role of epigenetic
      deregulation as a hallmark of haematological malignancies. The reversibility of
      epigenetic changes makes them suitable candidates for pharmacological
      manipulation and therapeutic targeting. AREAS COVERED: This review summarises the
      mechanisms of normal epigenetic regulation and how these are perturbed in
      haematological malignancies as a result of genetic alterations. The article
      concludes with how these can be reversed and appraises the investigational
      epigenetically targeted therapies in preclinical and clinical use. EXPERT
      OPINION: The identification of recurring alterations in components of the
      epigenome of leukaemia and lymphoma has driven the rapid development of highly
      potent epigenetically targeted therapies. This rapid development has alluded to
      the possibility of a personalised therapeutic approach in selected patient
      populations. An enhanced understanding of the biological effects of these
      epigenetic alterations in initiation and progression of haematological
      malignancies, together with a clear mechanistic insight into how the drugs
      reverse the phenotypes, will define their translation into routine clinical use.

PMID- 24855904
TI  - Groundwater salinity in a floodplain forest impacted by saltwater intrusion.
AB  - Coastal wetlands occupy a delicate position at the intersection of fresh and
      saline waters. Changing climate and watershed hydrology can lead to saltwater
      intrusion into historically freshwater systems, causing plant mortality and loss
      of freshwater habitat. Understanding the hydrological functioning of tidally
      influenced floodplain forests is essential for advancing ecosystem protection and
      restoration goals, however finding direct relationships between hydrological
      inputs and floodplain hydrology is complicated by interactions between surface
      water, groundwater, and atmospheric fluxes in variably saturated soils with
      heterogeneous vegetation and topography. Thus, an alternative method for
      identifying common trends and causal factors is required. Dynamic factor analysis
      (DFA), a time series dimension reduction technique, models temporal variation in
      observed data as linear combinations of common trends, which represent
      unexplained common variability, and explanatory variables. DFA was applied to
      model shallow groundwater salinity in the forested floodplain wetlands of the
      Loxahatchee River (Florida, USA), where altered watershed hydrology has led to
      changing hydroperiod and salinity regimes and undesired vegetative changes. Long
      term, high-resolution groundwater salinity datasets revealed dynamics over
      seasonal and yearly time periods as well as over tidal cycles and storm events.
      DFA identified shared trends among salinity time series and a full dynamic factor
      model simulated observed series well (overall coefficient of efficiency,
      Ceff=0.85; 0.52<=Ceff<=0.99). A reduced multilinear model based solely on
      explanatory variables identified in the DFA had fair to good results (Ceff=0.58;
      0.38<=Ceff<=0.75) and may be used to assess the effects of restoration and
      management scenarios on shallow groundwater salinity in the Loxahatchee River
      floodplain. 

PMID- 24855905
TI  - Effect of a reversal mirror condition on orofacial mechanical sensitivity.
AB  - The aim of this study was to investigate whether watching one's own face being
      touched in a reversal mirror condition modulates orofacial somatosensory
      sensitivity. A total of 37 healthy volunteers participated in a pilot study, the
      main study, and a control experiment. In the main experiment, 16 participants
      received seven different intensities of pinprick stimuli in the right
      infraorbital region. The perceived stimulus intensity was rated on a 0-50-100
      numerical rating scale (NRS). In addition, the pinprick threshold (PiPT) was
      evaluated in the same region using an electronic von Frey device. During stimuli,
      participants were watching their own face in two different conditions (normal and
      reversal mirror) in randomized order. Subjective experiences during each
      condition were assessed with a questionnaire containing nine statements. The
      participants rated their level of agreement with the statements using a 7-item
      Likert scale. There were significant main effects on NRS scores of stimulus
      forces (p < 0.001) and experimental condition (p < 0.001). Post hoc analyses
      showed that stimulation with higher force levels induced significantly higher NRS
      scores (p < 0.001), but interestingly, there were significantly lower NRS scores
      in the reversal mirror condition than in the normal mirror condition (p < 0.001).
      There was no significant main effect of experimental condition on PiPT (p =
      0.184). The experimental condition influenced the response to several statements
      significantly (p < 0.001). The somatosensory sensitivity may be impaired when the
      location of stimulation is not in accordance with the perception. In conclusion,
      hypoesthetic effects of a reversal mirror were present for fixed force measures
      but not for threshold measures. Further studies are now needed to describe the
      potential implications for other somatosensory modalities and orofacial pain
      conditions.

PMID- 24855906
TI  - Toll-like receptor-based adjuvants: enhancing the immune response to vaccines
      against infectious diseases of chicken.
AB  - Huge productivity loss due to infectious diseases in chickens is a major problem
      and, hence, robust development of the poultry industry requires control of
      poultry health. Immunization using vaccines is routine practice; however, to
      combat infectious diseases, conventional vaccines as well as new-generation
      recombinant vaccines alone, due to relatively weak immunogenicity, may not be
      effective enough to provide optimum immunity. With this in mind, there is a need
      to incorporate better and more suitable adjuvants in the vaccines to elicit the
      elevated immune response in the host. Over last few decades, with the increase in
      the knowledge of innate immune functioning, efforts have been made to enhance
      vaccine potency using novel adjuvants like Toll-like receptor based adjuvant
      systems. In this review, we will discuss the potential use of toll-like receptor
      ligands as an adjuvant in vaccines against the infectious diseases of chickens. 

PMID- 24855907
TI  - Subdominant hierarchical ovarian follicles are needed for steroidogenesis and
      ovulation in laying hens (Gallus domesticus).
AB  - Ovarian follicle development in avian species is characterized by a strict
      hierarchical arrangement. The hierarchical follicles secrete progesterone, which
      induces the LH surge, but the capacity to produce other steroids decreases with
      development. Our aim was to evaluate the complementary action of subdominant
      follicles (F4-F6) on ovulation and steroidogenesis of the preovulatory follicles
      (F1-F3) in domestic laying hens. The first study included four groups: control
      (C); sham-operated (SO); large hierarchical follicles (LHF) from which F4-F6
      follicles were extracted; and subdominant hierarchical follicles (SHF) from which
      F1-F3 follicles were extracted. Blood samples were collected every 2h from 12h
      before estimated ovoposition until 2h after ovoposition. Egg laying continued at
      the same rates in C and SO hens, with normal preovulatory surges of oestradiol,
      testosterone, progesterone and LH. In contrast, in LHF and SHF groups,
      ovoposition was blocked; oestradiol concentrations were not affected; but no
      preovulatory surges of testosterone, progesterone or LH were seen. Further, the
      testosterone surge was required for the occurrence of progesterone and LH surges.
      In the second study StAR and steroidogenic enzyme mRNA expression was evaluated
      within F1-F3 follicles from a LHF group and C-14 and C-8 controls groups, in
      which follicles were collected 14h and 8h before expected ovoposition,
      respectively. Extraction of F4-F6 follicles caused a significant reduction in
      StAR and 3beta-HSD expressions within theca, but not in granulosa cells. In
      conclusion, subdominant hierarchical follicles (F4-F6) are required for the
      preovulatory release of testosterone, progesterone and LH, which are highly inter
      correlated. 

PMID- 24855908
TI  - High-dose chemotherapy followed by autologous stem cell transplantation for
      patients with relapsed or refractory Hodgkin lymphoma: a systematic review with
      meta-analysis.
AB  - Treatment for Hodgkin lymphoma is effective for about 85% of the patients. A gold
      standard for the 15% of relapsing patients is still missing. High-dose
      chemotherapy (HDCT) followed by autologous stem cell transplantation (ASCT) has
      shown efficacy and safety for patients, but up to date no survival benefit
      revealed. After systematic literature search we identified three randomised
      controlled trials from 1663 total hits. Meta-analysis of two trials (157
      patients) showed a statistically significant increase in progression-free
      survival (hazard ratio 0.55, 95% confidence interval 0.35-0.86) for patients
      treated with HDCT and ASCT compared to conventional chemotherapy, but no
      difference in overall survival nor increased adverse events. The third trial (241
      patients) showed an statistically significant increase in infections and 5% more
      treatment-related mortalities following sequential HDCT plus HDCT and ASCT
      compared to HDCT plus ASCT, without differences in the efficacy endpoints overall
      survival or progression-free survival. 

PMID- 24855909
TI  - Regiospecific C-N photocyclization of 2-styrylquinolines.
AB  - Regiospecific C-N photocyclization of 2-styrylquinolines resulting in formation
      of potentially biologically active quino[1,2-a]quinolizinium derivatives was
      investigated. The presence of strong electron-donating groups in the phenyl ring
      reveals to be a crucial factor managing photocyclization effectiveness.
      Introduction of a crown ether moiety allows changing the photoreaction parameters
      by means of complexation with Mg(ClO4)2. 

PMID- 24855911
TI  - Genetic and ecologic variability among Anaplasma phagocytophilum strains,
      northern Italy.

PMID- 24855912
TI  - A retrospective comparative study of recombinant human thrombomodulin and
      gabexate mesilate in sepsis-induced disseminated intravascular coagulation
      patients.
AB  - The novel biological agent recombinant human thrombomodulin (rhTM) has been used
      clinically in Japan to treat disseminated intravascular coagulation (DIC) since
      2008. Previous studies have shown the efficacy of rhTM versus heparin therapy or
      non-rhTM therapy. We retrospectively evaluated and compared the efficacies of
      rhTM and gabexate mesilate (GM) in patients diagnosed with sepsis-induced DIC.
      From September 2010 to October 2012, patients with sepsis-induced DIC who were
      treated with rhTM (n = 13) or GM (n = 10) at Nagasaki Municipal Hospital were
      extracted. Patients receiving other anticoagulants in combination were excluded.
      Clinical information, laboratory data, Sequential Organ Failure Assessment (SOFA)
      scores, and DIC scores were obtained from the medical records. Mortality at days
      7 and 30 after DIC diagnosis and changes in laboratory data and SOFA scores from
      days 1-7 were evaluated. The groups' clinical characteristics did not differ,
      except for the relatively higher C-reactive protein (CRP) levels in the rhTM
      group (P = 0.0508). The survival rates of the rhTM and GM groups on days 7 and 30
      were 92.3%, 69.2% and 80%, 70%, respectively, both group indicated similar
      mortality. However, on day 7, the platelet counts, SOFA scores, and CRP levels
      significantly improved in the rhTM group; the platelet counts and SOFA scores did
      not improve significantly in the GM group. The platelet counts of the rhTM group
      significantly improved compared to the GM group (P = 0.004). Recombinant human
      thrombomodulin might be more effective for sepsis-induced DIC than GM.

PMID- 24855913
TI  - Recent trends in pediatric bacterial meningitis in Japan--a country where
      Haemophilus influenzae type b and Streptococcus pneumoniae conjugated vaccines
      have just been introduced.
AB  - To investigate the trends in incidence and the characteristics of bacterial
      meningitis in Japan where Haemophilus influenzae type b (Hib) vaccine and 7
      valent pneumococcal conjugated vaccine (PCV7) were introduced in 2008 and 2010,
      respectively, which was 5-20 years after their introduction in western countries.
      The nationwide Japanese survey of pediatric and neonatal bacterial meningitis was
      performed in 2011 and 2012. We analyzed the epidemiological and clinical data,
      and compared the information obtained in the previous nationwide survey database.
      We also investigated the risk factors for disease outcome. In the 2011-2012
      surveys, 357 patients were evaluated. H. influenzae, Streptococcus pneumoniae,
      Streptococcus agalactiae and Escherichia coli were the main organisms. The number
      of patients hospitalized with bacterial meningitis per 1000 admissions decreased
      from 1.31 in 2009 to 0.43 in 2012 (p < 0.001). The incidence of H. influenzae and
      S. pneumoniae meningitis also decreased from 0.66 to 0.08 (p < 0.001), and 0.30
      to 0.06 (p < 0.001), respectively. Only 0-2 cases with Neisseria meningitidis
      were reported each year throughout 2001-2012. The median patient age was 10-12
      months in 2001-2011, and became lower in 2012 (2 month old) (p < 0.001). The
      fatality rate for S. agalactiae is the highest (5.9% (11/187)) throughout 2001
      2012 among the four organisms. Risk factors for death and sequelae were
      convulsions at onset, low CSF glucose, S. agalactiae etiology, and persistent
      positive CSF culture. Hib vaccine and PCV7 decreased the rate of bacterial
      meningitis. Earlier introduction of these vaccines may have prevented bacterial
      meningitis among Japanese children.

PMID- 24855914
TI  - Effect of Ureaplasma parvum co-incubation on Chlamydia trachomatis maturation in
      human epithelial HeLa cells treated with interferon-gamma.
AB  - Chlamydia trachomatis is an obligate intracellular bacterium that causes a
      sexually transmitted disease. Ureaplasma parvum is commensal in the human genital
      tract, with a minimal contribution to urogenital infection. We have recently
      found that U. parvum has a significant effect on the presence of C. trachomatis
      in the genital tract of healthy women. We therefore assessed the effect of U.
      parvum co-incubation on C. trachomatis maturation from reticulate bodies (RBs) to
      elementary bodies (EBs) in HeLa cells in the absence or presence of interferon
      (IFN)-gamma, which is a critical host defense factor. IFN-gamma stimulation of
      viable U. parvum significantly prompted chlamydial growth with an increase in
      infectious particles, EBs, in HeLa cells. IFN-gamma treatment of killed U. parvum
      had a similar effect on C. trachomatis maturation in HeLa cells. There was no
      change in expression of indoleamine 2,3-dioxygenase (IDO) in cultures of viable
      or killed U. parvum. We concluded that U. parvum co-incubation by IFN-gamma
      helped C. trachomatis to mature from RBs to EBs in HeLa cells, independent of IDO
      expression. This suggests a novel survival strategy of C. trachomatis against IFN
      gamma exposure, prompting secondary infection of the genital mucosa, with
      possible clinical implications.

PMID- 24855915
TI  - Skin rash related to once-daily boosted darunavir-containing antiretroviral
      therapy in HIV-infected Taiwanese: incidence and associated factor.
AB  - OBJECTIVES: The study aimed to investigate the incidence of and associated
      factors with skin rashes among HIV-infected Taiwanese patients who received once
      daily darunavir (DRV) boosted by ritonavir (RTV) (800/100 mg) plus 2 nucleoside
      reverse-transcriptase inhibitors (NRTIs). METHODS: We reviewed the medical
      records of HIV-infected patients who switched to once-daily DRV/RTV-containing
      regimens between January 2012 and November 2013. Patients who switched from 2
      NRTIs plus non-NRTI (nNRTI) or other protease inhibitor (PI) to 2 NRTIs plus PIs
      other than DRV were chosen as comparators. RESULTS: During the study period, 238
      patients who switched to once-daily DRV/RTV-containing regimens (Group A) and 178
      patients who switched from 2 NRTIs plus nNRTI or other PI to 2 NRTIs plus PI
      other than DRV/RTV (Group B) were included. There were no differences between
      Groups A and B in most of the baseline characteristics. Compared with Group B in
      which 7 (3.9%) developed rashes after switch to PI other than DRV, 26 patients
      (10.9%) in Group A developed rashes after a median interval of 14 days of
      starting DRV/RTV-containing regimens (P = 0.009). In multivariate analysis,
      patients with a history of rashes related to the previous nNRTI-containing
      regimens before starting DRV/RTV-containing regimens were more likely to develop
      rashes with an adjusted odds ratio of 3.53 (95% confidence interval, 1.45-8.62).
      CONCLUSIONS: Once-daily regimens containing DRV/RTV is associated with a higher
      rate of adverse cutaneous reactions than other PI-containing regimens in HIV
      infected Taiwanese, especially in those who have a history of rashes to nNRTI
      containing regimens before switch to DRV/RTV-containing regimens.

PMID- 24855916
TI  - A case of community-acquired pneumonia due to influenza A virus and Nocardia
      farcinica co-infection.
AB  - Nocardia spp. has not been reported previously as a cause of post-influenza
      pneumonia. Here we present a first case of post-influenza bacterial pneumonia due
      to Nocardia farcinica. Initial reason for hospitalization of the 90 year old
      female patient was a pneumonia with the symptoms of fever and productive cough. A
      rapid test for influenza antigen was positive for influenza A virus. Treatment
      with Zanamivir and piperacillin was initiated. However, after 1 week of
      treatment, the infiltration shadows on chest X-ray had worsened. Because the
      expectorated sputum collected on admission for culture was found to be positive
      for Nocardia spp., piperacillin was replaced with trimethoprim/sulfamethoxazole,
      and a chest X-ray showed some improvement. Although pulmonary nocardiosis with co
      infection with influenza A is extremely rare, clinicians should be alert to the
      possibility.

PMID- 24855924
TI  - United States biomedical research impacting child health and the growth of the
      National Institutes of Health funding to pediatric departments and children's
      hospitals.

PMID- 24855925
TI  - 50 years ago in the Journal of pediatrics: Drug testing in animals for
      teratogenic effects. Thalidomide in the pregnant rat.

PMID- 24855926
TI  - 50 years ago in the Journal of pediatrics: Ketotic hypoglycemia.

PMID- 24855927
TI  - 50 years ago in the Journal of pediatrics: The nature of kidney disease in
      children who fail to recover from apparent acute glomerulonephritis.

PMID- 24855928
TI  - 50 years ago in the Journal of pediatrics: The incidence of neonatal hypoglycemia
      in a nursery for premature infants.

PMID- 24855929
TI  - Bias and small-study effects influence treatment effect estimates: a meta
      epidemiological study in oral medicine.
AB  - OBJECTIVES: To examine the influence of the following study characteristics on
      their study effect estimates: (1) indexing in MEDLINE, (2) language, and (3)
      design. For randomized trials, (4) trial size and (5) unequal randomization were
      also assessed. STUDY DESIGN AND SETTING: The CAtegorical Dental and Maxillofacial
      Outcome Syntheses meta-epidemiologic study was conducted. Eight
      databases/registers were searched up to September 2012 for meta-analyses of
      binary outcomes with at least five studies in the field of dental and
      maxillofacial medicine. The previously mentioned five study characteristics were
      investigated. The ratio of odds ratios (ROR) according to each characteristic was
      calculated with random-effects meta-regression and then pooled across meta
      analyses. RESULTS: A total of 281 meta-analyses were identified and used to
      assess the influence of the following factors: non-MEDLINE indexing vs. MEDLINE
      indexing (n = 78; ROR, 1.12; 95% confidence interval [CI]: 1.05, 1.19; P =
      0.001), language (n = 61; P = 0.546), design (n = 24; P = 0.576), small trials
      (<200 patients) vs. large trials (>=200 patients) (n = 80; ROR, 0.92; 95% CI:
      0.87, 0.98; P = 0.009) and unequal randomization (n = 36; P = 0.828). CONCLUSION:
      Studies indexed in MEDLINE might present greater effects than non-indexed ones.
      Small randomized trials might present greater effects than large ones.

PMID- 24855930
TI  - Risk factors for development of methicillin-resistant Staphylococcus aureus
      positive clinical culture in nasal carriers after decolonization treatment.
AB  - BACKGROUND: Active surveillance systems are effective in reducing health care
      associated infections caused by methicillin-resistant Staphylococcus aureus
      (MRSA). Nonetheless, some patients develop MRSA infection despite control
      measures. We tried to identify risk factors related to the appearance of MRSA at
      sites other than the nasal fossa in patients who were nasal carriers of MRSA.
      METHODS: A retrospective case-control study was conducted in an active
      surveillance program for MRSA between January 2009 and December 2010 at a Spanish
      teaching hospital. Cases were patients with MRSA in the anterior nares and a
      length of stay of at least 5 days who developed MRSA-positive clinical culture
      after decolonization treatment had started. Controls were patients with the same
      characteristics as the case group, except that they did not develop MRSA-positive
      clinical culture as verified by negative clinical cultures. RESULTS: After
      intrinsic and extrinsic risk factors were analyzed, the emergence of mupirocin
      resistant MRSA clones after decolonization treatment, and residence in a nursing
      home were marginally significant in the univariate analysis. The detection of the
      emergence of mupirocin-resistant MRSA clones was independently associated with
      the detection of MRSA in other clinical locations. CONCLUSIONS: In an active
      surveillance program for MRSA it is important to determine the mupirocin
      susceptibility of the isolates to determine appropriate treatment and to verify
      negativity after decolonizing treatment has been completed.

PMID- 24855931
TI  - Nursing students' intentions to comply with standard precautions: an exploratory
      prospective cohort study.
AB  - BACKGROUND: Partial compliance of health care workers with standard precaution
      (SP) guidelines has been extensively documented. The aim of this study was to
      describe the development of nursing students' intentions to comply with SPs.
      METHODS: Prospective cohort study. Two consecutive classes of a 4-year bachelor
      of nursing program completed questionnaires 3 times. The transtheoretical model
      of change was used to describe the change in intentions to comply with SPs.
      Factor analysis displayed 2 behavioral categories: commonly used standard
      precautions (CUSPs) and less commonly used standard precautions (LUSPs).
      Knowledge, risk perception, sense of coherence (SOC), safety climate (SC), and
      emphasis given by educators were evaluated as associated factors. RESULTS: Of the
      91 students, 85 (93%) completed the questionnaire during their second year, 57 of
      88 students (65%) completed it during the third year, and 70 of 82 students (85%)
      completed it at the end of the fourth year. Of the 82 students, 45 (55%)
      completed 3 measurements. CUSPs exhibited a rise from the second to the third
      year, with a moderate decline from the third to the fourth year, whereas LUSPs
      continued ascending. CUSPs were positively associated with SC and SOC; LUSPs were
      commonly associated with risk perception. CONCLUSION: The different evolution of
      CUSPs and LUSPs and dissimilar associations may suggest that different strategies
      might encourage diverse SP behaviors. Improving the SC might be appropriate when
      aiming to encourage CUSPs, and highlighting risks may be appropriate to encourage
      LUSPs.

PMID- 24855932
TI  - Health care-associated respiratory infection surveillance among Chinese children
      with cerebral palsy.
AB  - BACKGROUND: To explore the characteristics and distribution of hospital length of
      stay (LOS) and direct hospitalization costs of children with cerebral palsy (CP)
      affected by health care-associated infection (HAI). METHODS: A prospective
      observational study was performed from March 2010 to February 2012 on HAI cases
      among hospitalized children with CP. Demographic, clinical, and HAI data were
      recorded. Mann-Whitney test, chi-square test, and multiple linear regressions
      were used for data analysis. RESULTS: Of 528 patients with CP, 151 (28.6%)
      suffered HAI in the form of respiratory tract infection. Male to female ratio was
      2.87. About 50 patients had recurrent HAI. Upper respiratory infection and
      pneumonia were common infections. HAI occurring more than once contributed mainly
      to total LOS, and the length of HAI was >10 days in >50% of patients. Frequency
      of HAI was an independent predictor of LOS, and frequency of HAI and LOS were
      independent predictors of hospitalization costs. CONCLUSION: Health care
      associated respiratory infection significantly impacted LOS and total cost of
      children with CP admitted for rehabilitation. These data should assist in
      establishing preventive and control measures for HAI to help improve the quality
      of rehabilitation and survival in the long run.

PMID- 24855933
TI  - Chondrocyte and mesenchymal stem cell-based therapies for cartilage repair in
      osteoarthritis and related orthopaedic conditions.
AB  - Osteoarthritis (OA) represents a final and common pathway for all major traumatic
      insults to synovial joints. OA is the most common form of degenerative joint
      disease and a major cause of pain and disability. Despite the global increase in
      the incidence of OA, there are no effective pharmacotherapies capable of
      restoring the original structure and function of damaged articular cartilage.
      Consequently cell-based and biological therapies for osteoarthritis (OA) and
      related orthopaedic disorders have become thriving areas of research and
      development. Autologous chondrocyte implantation (ACI) has been used for
      treatment of osteoarticular lesions for over two decades. Although chondrocyte
      based therapy has the capacity to slow down the progression of OA and delay
      partial or total joint replacement surgery, currently used procedures are
      associated with the risk of serious adverse events. Complications of ACI include
      hypertrophy, disturbed fusion, delamination, and graft failure. Therefore there
      is significant interest in improving the success rate of ACI by improving
      surgical techniques and preserving the phenotype of the primary chondrocytes used
      in the procedure. Future tissue-engineering approaches for cartilage repair will
      also benefit from advances in chondrocyte-based repair strategies. This review
      article focuses on the structure and function of articular cartilage and the
      pathogenesis of OA in the context of the rising global burden of musculoskeletal
      disease. We explore the challenges associated with cartilage repair and
      regeneration using cell-based therapies that use chondrocytes and mesenchymal
      stem cells (MSCs). This paper also explores common misconceptions associated with
      cell-based therapy and highlights a few areas for future investigation. 

PMID- 24855934
TI  - Dual-peak electrogenerated chemiluminescence of carbon dots for iron ions
      detection.
AB  - Carbon dots (CDs) have rigorously been investigated on their unique fluorescent
      properties but rarely their electrogenerated chemiluminescence (ECL) behavior. We
      are here to report a dual-peak ECL system of CDs, one at -2.84 V (ECL-1) and the
      other at -1.71 V (ECL-2) during the cyclic sweep between -3.0 and 3.0 V at scan
      rate of 0.2 V s(-1) in 0.1 M tetrabutyl ammonium bromide (TBAB) ethanol solution,
      which is more efficiency to distinguish metallic ions than single-peak ECL. The
      electron transfer reaction between individual electrochemically reduced
      nanocrystal species and coreactants led to ECL-1, in which the electron injected
      to the conduction band of CDs in the cathodic process. Ion annihilation reactions
      induced direct formation of exciplexes that produced another ECL signal, ECL-2.
      ECL-1 showed higher sensitivity to the surrounding environment than ECL-2 and
      thus was used for ECL detection of metallic ions. Herein, we can serve as an
      internal standard method to detect iron ions. A linear relationship of the
      intensity ratio R of ECL-1 and ECL-2 to iron ions was observed in the
      concentration extending from 5 * 10(-6) to 8 * 10(-5) M with a detection limit of
      7 * 10(-7) M. 

PMID- 24855935
TI  - Species H rotavirus detected in piglets with diarrhea, Brazil, 2012.
AB  - We determined nucleotide and deduced amino acid sequences of the rotavirus gene
      encoding viral protein 6 from 3 fecal samples collected from piglets with
      diarrhea in Brazil, 2012. The analyses showed that the porcine rotavirus strains
      in Brazil are closely related to the novel species H rotavirus. 

PMID- 24855937
TI  - Die another day: a painless path to longevity.
AB  - Riera et al. identify a neuroendocrine circuit that controls longevity and the
      age-dependent onset of metabolic decline via the pain-transducing channel TRPV1.
      Thus, pharmacological inhibition of TRPV1 may provide a new approach to treat not
      only metabolic disorders but also a broader range of age-related pathologies.

PMID- 24855936
TI  - Effects of biopretreatment on pyrolysis behaviors of corn stalk by methanogen.
AB  - The study investigated the effects of methanogen pretreatment on pyrolysis
      behaviors of corn stalk (CS) by using Py-GC/MS analysis and thermogravimetric
      analysis. Results indicated that biopretreatment changed considerably the
      pyrolysis behaviors of CS from four weight loss stages to two weight loss stages.
      Increasing biopretreatment time from 5 days to 25 days enhanced the kinds and
      contents of chemicals in volatile products. In pyrolysis products, the contents
      of sugars, linear ketones and furans decreased from 1.43%, 12.60% and 7.38% to
      1.25%, 10.22% and 3.25%, respectively, and the contents of phenols increased from
      15.08% to 27.84%. The most content change from 6.83% to 13.63% indicated that
      methanogen pretreatment improved the pyrolysis selectivity of CS to product the 4
      VP, but it was disadvantageous to 5-hydroxymethyl furfural, levoglucose and
      furfural. The changes of chemical compositions and structure of CS after
      biopretreatment were the main reason of the differences.

PMID- 24855939
TI  - The engine of microtubule dynamics comes into focus.
AB  - In this issue, Alushin et al. report high-resolution structures of three states
      of the microtubule lattice: GTP-bound, which is stable to depolymerization;
      unstable GDP-bound; and stable Taxol and GDP-bound. By comparing these structures
      at near-atomic resolution, they are able to propose a detailed model for how GTP
      hydrolysis destabilizes the microtubule and thus powers dynamic instability and
      chromosome movement. Destabilization of cytoskeleton filaments by nucleotide
      hydrolysis is an important general principle in cell dynamics, and this work
      represents a major step forward on a problem with a long history.

PMID- 24855938
TI  - Focusing in on T cell cross-reactivity.
AB  - To provide broad immunity to a vast array of foreign antigens with a limited
      number of T lymphocytes, each cell has to recognize many targets. By implementing
      a strategy to identify T cell receptor (TCR) ligands and investigating at a fine
      granularity their structure and sequence relationship, Birnbaum et al.
      demonstrate the surprisingly tight focus of such T cell cross-reactivity.

PMID- 24855940
TI  - Tempering temperature changes for robust development.
AB  - Developmental signaling pathways needed to evolve to be robust against
      environmental fluctuations. In this issue, Shimizu et al. reveal a complex system
      of interacting endocytic pathways that help to maintain consistent levels of
      Notch activity across a range of temperatures.

PMID- 24855941
TI  - Mechanisms and functions of inflammasomes.
AB  - Recent studies have offered a glimpse into the sophisticated mechanisms by which
      inflammasomes respond to danger and promote secretion of interleukin (IL)-1beta
      and IL-18. Activation of caspases 1 and 11 in canonical and noncanonical
      inflammasomes, respectively, also protects against infection by triggering
      pyroptosis, a proinflammatory and lytic mode of cell death. The therapeutic
      potential of inhibiting these proinflammatory caspases in infectious and
      autoimmune diseases is raised by the successful deployment of anti-IL-1 therapies
      to control autoinflammatory diseases associated with aberrant inflammasome
      signaling. This Review summarizes recent insights into inflammasome biology and
      discusses the questions that remain in the field. 

PMID- 24855942
TI  - TRPV1 pain receptors regulate longevity and metabolism by neuropeptide signaling.
AB  - The sensation of pain is associated with increased mortality, but it is unknown
      whether pain perception can directly affect aging. We find that mice lacking
      TRPV1 pain receptors are long-lived, displaying a youthful metabolic profile at
      old age. Loss of TRPV1 inactivates a calcium-signaling cascade that ends in the
      nuclear exclusion of the CREB-regulated transcriptional coactivator CRTC1 within
      pain sensory neurons originating from the spinal cord. In long-lived TRPV1
      knockout mice, CRTC1 nuclear exclusion decreases production of the neuropeptide
      CGRP from sensory endings innervating the pancreatic islets, subsequently
      promoting insulin secretion and metabolic health. In contrast, CGRP homeostasis
      is disrupted with age in wild-type mice, resulting in metabolic decline. We show
      that pharmacologic inactivation of CGRP receptors in old wild-type animals can
      restore metabolic health. These data suggest that ablation of select pain sensory
      receptors or the inhibition of CGRP are associated with increased metabolic
      health and control longevity. 

PMID- 24855943
TI  - Molecular mechanism of action of plant DRM de novo DNA methyltransferases.
AB  - DNA methylation is a conserved epigenetic gene-regulation mechanism. DOMAINS
      REARRANGED METHYLTRANSFERASE (DRM) is a key de novo methyltransferase in plants,
      but how DRM acts mechanistically is poorly understood. Here, we report the
      crystal structure of the methyltransferase domain of tobacco DRM (NtDRM) and
      reveal a molecular basis for its rearranged structure. NtDRM forms a functional
      homodimer critical for catalytic activity. We also show that Arabidopsis DRM2
      exists in complex with the small interfering RNA (siRNA) effector ARGONAUTE4
      (AGO4) and preferentially methylates one DNA strand, likely the strand acting as
      the template for RNA polymerase V-mediated noncoding RNA transcripts. This strand
      biased DNA methylation is also positively correlated with strand-biased siRNA
      accumulation. These data suggest a model in which DRM2 is guided to target loci
      by AGO4-siRNA and involves base-pairing of associated siRNAs with nascent RNA
      transcripts. 

PMID- 24855944
TI  - The TRPM7 chanzyme is cleaved to release a chromatin-modifying kinase.
AB  - TRPM7 is a ubiquitous ion channel and kinase, a unique "chanzyme," required for
      proper early embryonic development. It conducts Zn(2+), Mg(2+), and Ca(2+) as
      well as monovalent cations and contains a functional serine/threonine kinase at
      its carboxyl terminus. Here, we show that in normal tissues and cell lines, the
      kinase is proteolytically cleaved from the channel domain in a cell-type-specific
      manner. These TRPM7 cleaved kinase fragments (M7CKs) translocate to the nucleus
      and bind multiple components of chromatin-remodeling complexes, including
      Polycomb group proteins. In the nucleus, the kinase phosphorylates specific
      serines/threonines of histones. M7CK-dependent phosphorylation of H3Ser10 at
      promoters of TRPM7-dependent genes correlates with their activity. We also
      demonstrate that cytosolic free [Zn(2+)] is TRPM7 dependent and regulates M7CK
      binding to transcription factors containing zinc-finger domains. These findings
      suggest that TRPM7-mediated modulation of intracellular Zn(2+) concentration
      couples ion-channel signaling to epigenetic chromatin covalent modifications that
      affect gene expression patterns. PAPERCLIP: 

PMID- 24855945
TI  - Deconstructing the peptide-MHC specificity of T cell recognition.
AB  - In order to survey a universe of major histocompatibility complex (MHC)-presented
      peptide antigens whose numbers greatly exceed the diversity of the T cell
      repertoire, T cell receptors (TCRs) are thought to be cross-reactive. However,
      the nature and extent of TCR cross-reactivity has not been conclusively measured
      experimentally. We developed a system to identify MHC-presented peptide ligands
      by combining TCR selection of highly diverse yeast-displayed peptide-MHC
      libraries with deep sequencing. Although we identified hundreds of peptides
      reactive with each of five different mouse and human TCRs, the selected peptides
      possessed TCR recognition motifs that bore a close resemblance to their known
      antigens. This structural conservation of the TCR interaction surface allowed us
      to exploit deep-sequencing information to computationally identify activating
      microbial and self-ligands for human autoimmune TCRs. The mechanistic basis of
      TCR cross-reactivity described here enables effective surveillance of diverse
      self and foreign antigens without necessitating degenerate recognition of
      nonhomologous peptides.

PMID- 24855946
TI  - Protein and nucleotide biosynthesis are coupled by a single rate-limiting enzyme,
      PRPS2, to drive cancer.
AB  - Cancer cells must integrate multiple biosynthetic demands to drive indefinite
      proliferation. How these key cellular processes, such as metabolism and protein
      synthesis, crosstalk to fuel cancer cell growth is unknown. Here, we uncover the
      mechanism by which the Myc oncogene coordinates the production of the two most
      abundant classes of cellular macromolecules, proteins, and nucleic acids in
      cancer cells. We find that a single rate-limiting enzyme, phosphoribosyl
      pyrophosphate synthetase 2 (PRPS2), promotes increased nucleotide biosynthesis in
      Myc-transformed cells. Remarkably, Prps2 couples protein and nucleotide
      biosynthesis through a specialized cis-regulatory element within the Prps2 5'
      UTR, which is controlled by the oncogene and translation initiation factor eIF4E
      downstream Myc activation. We demonstrate with a Prps2 knockout mouse that the
      nexus between protein and nucleotide biosynthesis controlled by PRPS2 is crucial
      for Myc-driven tumorigenesis. Together, these studies identify a translationally
      anchored anabolic circuit critical for cancer cell survival and an unexpected
      vulnerability for "undruggable" oncogenes, such as Myc. PAPERFLICK:

PMID- 24855947
TI  - An essential mesenchymal function for miR-143/145 in intestinal epithelial
      regeneration.
AB  - Downregulation of the miR-143/145 microRNA (miRNA) cluster has been repeatedly
      reported in colon cancer and other epithelial tumors. In addition, overexpression
      of these miRNAs inhibits tumorigenesis, leading to broad consensus that they
      function as cell-autonomous epithelial tumor suppressors. We generated mice with
      deletion of miR-143/145 to investigate the functions of these miRNAs in
      intestinal physiology and disease in vivo. Although intestinal development
      proceeded normally in the absence of these miRNAs, epithelial regeneration after
      injury was dramatically impaired. Surprisingly, we found that miR-143/145 are
      expressed and function exclusively within the mesenchymal compartment of
      intestine. Defective epithelial regeneration in miR-143/145-deficient mice
      resulted from the dysfunction of smooth muscle and myofibroblasts and was
      associated with derepression of the miR-143 target Igfbp5, which impaired IGF
      signaling after epithelial injury. These results provide important insights into
      the regulation of epithelial wound healing and argue against a cell-autonomous
      tumor suppressor role for miR-143/145 in colon cancer.

PMID- 24855948
TI  - High-resolution microtubule structures reveal the structural transitions in
      alphabeta-tubulin upon GTP hydrolysis.
AB  - Dynamic instability, the stochastic switching between growth and shrinkage, is
      essential for microtubule function. This behavior is driven by GTP hydrolysis in
      the microtubule lattice and is inhibited by anticancer agents like Taxol. We
      provide insight into the mechanism of dynamic instability, based on high
      resolution cryo-EM structures (4.7-5.6 A) of dynamic microtubules and
      microtubules stabilized by GMPCPP or Taxol. We infer that hydrolysis leads to a
      compaction around the E-site nucleotide at longitudinal interfaces, as well as
      movement of the alpha-tubulin intermediate domain and H7 helix. Displacement of
      the C-terminal helices in both alpha- and beta-tubulin subunits suggests an
      effect on interactions with binding partners that contact this region. Taxol
      inhibits most of these conformational changes, allosterically inducing a GMPCPP
      like state. Lateral interactions are similar in all conditions we examined,
      suggesting that microtubule lattice stability is primarily modulated at
      longitudinal interfaces.

PMID- 24855949
TI  - A code for RanGDP binding in ankyrin repeats defines a nuclear import pathway.
AB  - Regulation of nuclear import is fundamental to eukaryotic biology. The majority
      of nuclear import pathways are mediated by importin-cargo interactions. Yet not
      all nuclear proteins interact with importins, necessitating the identification of
      a general importin-independent nuclear import pathway. Here, we identify a code
      that determines importin-independent nuclear import of ankyrin repeats (ARs), a
      structural motif found in over 250 human proteins with diverse functions. AR
      containing proteins (ARPs) with a hydrophobic residue at the 13th position of two
      consecutive ARs bind RanGDP efficiently, and consequently enter the nucleus. This
      code, experimentally tested in 17 ARPs, predicts the nuclear-cytoplasmic
      localization of over 150 annotated human ARPs with high accuracy and is acquired
      by the most common familial melanoma-associated CDKN2A mutation, leading to
      nuclear accumulation of mutant p16ink4a. The RaDAR (RanGDP/AR) pathway represents
      a general importin-independent nuclear import pathway and is frequently used by
      AR-containing transcriptional regulators, especially those regulating NF
      kappaB/p53.

PMID- 24855950
TI  - Mechanical feedback through E-cadherin promotes direction sensing during
      collective cell migration.
AB  - E-cadherin is a major homophilic cell-cell adhesion molecule that inhibits
      motility of individual cells on matrix. However, its contribution to migration of
      cells through cell-rich tissues is less clear. We developed an in vivo sensor of
      mechanical tension across E-cadherin molecules, which we combined with cell-type
      specific RNAi, photoactivatable Rac, and morphodynamic profiling, to interrogate
      how E-cadherin contributes to collective migration of cells between other cells.
      Using the Drosophila ovary as a model, we found that adhesion between border
      cells and their substrate, the nurse cells, functions in a positive feedback loop
      with Rac and actin assembly to stabilize forward-directed protrusion and
      directionally persistent movement. Adhesion between individual border cells
      communicates direction from the lead cell to the followers. Adhesion between
      motile cells and polar cells holds the cluster together and polarizes each
      individual cell. Thus, E-cadherin is an integral component of the guidance
      mechanisms that orchestrate collective chemotaxis in vivo.

PMID- 24855951
TI  - Compensatory flux changes within an endocytic trafficking network maintain
      thermal robustness of Notch signaling.
AB  - Developmental signaling is remarkably robust to environmental variation,
      including temperature. For example, in ectothermic animals such as Drosophila,
      Notch signaling is maintained within functional limits across a wide temperature
      range. We combine experimental and computational approaches to show that
      temperature compensation of Notch signaling is achieved by an unexpected variety
      of endocytic-dependent routes to Notch activation which, when superimposed on
      ligand-induced activation, act as a robustness module. Thermal compensation
      arises through an altered balance of fluxes within competing trafficking routes,
      coupled with temperature-dependent ubiquitination of Notch. This flexible
      ensemble of trafficking routes supports Notch signaling at low temperature but
      can be switched to restrain Notch signaling at high temperature and thus
      compensates for the inherent temperature sensitivity of ligand-induced
      activation. The outcome is to extend the physiological range over which normal
      development can occur. Similar mechanisms may provide thermal robustness for
      other developmental signals. 

PMID- 24855952
TI  - Interaction of circadian clock proteins CRY1 and PER2 is modulated by zinc
      binding and disulfide bond formation.
AB  - Period (PER) proteins are essential components of the mammalian circadian clock.
      They form complexes with cryptochromes (CRY), which negatively regulate
      CLOCK/BMAL1-dependent transactivation of clock and clock-controlled genes. To
      define the roles of mammalian CRY/PER complexes in the circadian clock, we have
      determined the crystal structure of a complex comprising the photolyase homology
      region of mouse CRY1 (mCRY1) and a C-terminal mouse PER2 (mPER2) fragment. mPER2
      winds around the helical mCRY1 domain covering the binding sites of FBXL3 and
      CLOCK/BMAL1, but not the FAD binding pocket. Our structure revealed an unexpected
      zinc ion in one interface, which stabilizes mCRY1-mPER2 interactions in vivo. We
      provide evidence that mCRY1/mPER2 complex formation is modulated by an interplay
      of zinc binding and mCRY1 disulfide bond formation, which may be influenced by
      the redox state of the cell. Our studies may allow for the development of
      circadian and metabolic modulators.

PMID- 24855955
TI  - SnapShot: nuclear RNAPII transcript modification.
AB  - RNA polymerase II generates a diverse set of RNA transcripts, including mRNA,
      miRNA, lncRNA, and sn(o)RNA. These transcripts are modified and processed in the
      nucleus by a particular set of enzymes, as illustrated in this SnapShot. 

PMID- 24855953
TI  - Npas4 regulates excitatory-inhibitory balance within neural circuits through cell
      type-specific gene programs.
AB  - The nervous system adapts to experience by inducing a transcriptional program
      that controls important aspects of synaptic plasticity. Although the molecular
      mechanisms of experience-dependent plasticity are well characterized in
      excitatory neurons, the mechanisms that regulate this process in inhibitory
      neurons are only poorly understood. Here, we describe a transcriptional program
      that is induced by neuronal activity in inhibitory neurons. We find that, while
      neuronal activity induces expression of early-response transcription factors such
      as Npas4 in both excitatory and inhibitory neurons, Npas4 activates distinct
      programs of late-response genes in inhibitory and excitatory neurons. These late
      response genes differentially regulate synaptic input to these two types of
      neurons, promoting inhibition onto excitatory neurons while inducing excitation
      onto inhibitory neurons. These findings suggest that the functional outcomes of
      activity-induced transcriptional responses are adapted in a cell-type-specific
      manner to achieve a circuit-wide homeostatic response. 

PMID- 24855956
TI  - A modified Delphi consensus study to identify UK osteopathic profession research
      priorities.
AB  - There is an increasing emphasis to take an evidence-based approach to healthcare.
      To obtain evidence relevant to the osteopathic profession a clear research
      direction is required based on the views of stakeholders in the osteopathic
      profession. A modified Delphi consensus approach was conducted to explore the
      views of osteopaths and patients regarding research priorities for osteopathy.
      Osteopaths and patients were invited to complete an online questionnaire survey
      (n = 145). Round 1 requested up to 10 research priority areas and the rationale
      for their selection. All of the themes from Round 1 were fed back verbatim, and
      in Round 2 participants were asked to rank the importance of the research
      priorities on a 5-point Likert scale. Finally, in Round 3 participants were asked
      to rank the importance of a refined list of research topics which had reached
      consensus. Descriptive analysis and use of Kendall's coefficient of concordance
      enabled interpretation of consensus. The response rate for Round 1 was 87.9% and
      identified 610 research priority areas. Round 2 identified 69 research themes as
      important, and Round 3 identified 20 research priority topic areas covering four
      themes: effectiveness of osteopathic treatment (7 areas prioritised), role of
      osteopathy: the management of four conditions were prioritised, risks with
      osteopathic treatment (two areas prioritised) and outcomes of osteopathic
      treatment (two areas prioritised). The findings will be taken forward to develop
      the research strategy for osteopathy. 

PMID- 24855957
TI  - NK-1 receptor may have a role in perineural invasion in malignant salivary gland.

PMID- 24855958
TI  - The process of writing an abstract.

PMID- 24855954
TI  - Molecular profiling of neurons based on connectivity.
AB  - The complexity and cellular heterogeneity of neural circuitry presents a major
      challenge to understanding the role of discrete neural populations in controlling
      behavior. While neuroanatomical methods enable high-resolution mapping of neural
      circuitry, these approaches do not allow systematic molecular profiling of
      neurons based on their connectivity. Here, we report the development of an
      approach for molecularly profiling projective neurons. We show that ribosomes can
      be tagged with a camelid nanobody raised against GFP and that this system can be
      engineered to selectively capture translating mRNAs from neurons retrogradely
      labeled with GFP. Using this system, we profiled neurons projecting to the
      nucleus accumbens. We then used an AAV to selectively profile midbrain dopamine
      neurons projecting to the nucleus accumbens. By comparing the captured mRNAs from
      each experiment, we identified a number of markers specific to VTA dopaminergic
      projection neurons. The current method provides a means for profiling neurons
      based on their projections. 

PMID- 24855959
TI  - Visualizing the endocytosis of phenylephrine in living cells by quantum dot-based
      tracking.
AB  - To study the intracellular receptor-drug transportation, a fluorescent probe
      consisting of phenylephrine-polyethylene glycol-quantum dots conjugate was
      employed to track endocytosis process of phenylephrine in living cells. This type
      of movement was studied by continuously filming fluorescent images in the same
      cell. We also calculated the movement parameters, and divided the endocytosis
      process into 6 stages. Furthermore, the movement parameters of this probe in
      different organelles were determined by co-localization of the probe fluorescent
      images and different cellular organelles. After comparing the parameters in
      cellular organelles with these in 6 stages, the whole endocytosis pathway was
      demonstrated. These results verified that this probe successfully tracked the
      whole intracellular dynamic endocytosis process of phenylephrine. Our method
      realized the visual tracking the whole receptor-mediated endocytosis, which is a
      new approach on investigating the molecular mechanisms and kinetic properties of
      intracellular receptor-drug transportation. 

PMID- 24855960
TI  - Decellularized kidney scaffold-mediated renal regeneration.
AB  - Renal regeneration approaches offer great potential for the treatment of chronic
      kidney disease, but their availability remains limited by the clinical challenges
      they pose. In the present study, we used continuous detergent perfusion to
      generate decellularized (DC) rat kidney scaffolds. The scaffolds retained intact
      vascular trees and overall architecture, along with significant concentrations of
      various cytokines, but lost all cellular components. To evaluate its potential in
      renal function recovery, DC scaffold tissue was grafted onto partially
      nephrectomized rat kidneys. An increase of renal size was found, and regenerated
      renal parenchyma cells were observed in the repair area containing the grafted
      scaffold. In addition, the number of nestin-positive renal progenitor cells was
      markedly higher in scaffold-grafted kidneys compared to controls. Moreover,
      radionuclide scan analysis showed significant recovery of renal functions at 6
      weeks post-implantation. Our results provide further evidence to show that DC
      kidney scaffolds could be used to promote renal recovery in the treatment of
      chronic kidney disease. 

PMID- 24855965
TI  - Vascularized medial femoral trochlea osteochondral flap reconstruction of
      advanced Kienbock disease.
AB  - PURPOSE: To describe the operative technique and report the results of 16
      consecutive cases of arthroplasty for advanced Kienbock disease using a
      vascularized osteochondral graft from the medial femoral trochlea (MFT) with a
      minimum 12-month follow-up. METHODS: Chart reviews of 16 cases of osteochondral
      MFT flap transfers for lunate reconstruction were performed in 2 institutions.
      Mean patient age was 35 years (range, 19-51 y). Preoperative Lichtman staging was
      2 in 7 patients, 3a in 8 patients, and 3b in 1. Five of 16 patients had undergone
      a previous procedure for Kienbock disease (3 radial shortening osteotomies, 1
      wrist denervation, and 1 distal radius vascularized bone grafting). Ulnar
      variance recorded at the time of the MFT reconstruction was negative in 8
      patients, positive in 6 patients, and neutral in 2 patients. Follow-up data were
      recorded at a minimum of 12 months (average, 19 mo). Radiographic parameters
      recorded included preoperative ulnar variance, preoperative and final follow-up
      radioscaphoid angle, lunate height, lunate diameter, and the Stahl index and
      Lichtman stage. RESULTS: Healing was confirmed in 15 of 16 reconstructed lunates.
      Lichtman staging remained unchanged in 10 patients, improved in 4 patients from
      grade 3a and 3b to 2, and worsened in 2 patients from grade 3a to 3b. All but 1
      patient experienced improvement in wrist pain (12/16 complete relief; 3/16
      incomplete relief). Wrist motion at follow-up averaged 50 degrees  extension and
      38 degrees  flexion, similar to preoperative measurements. Grip strength at
      follow-up was 85% of the contralateral side. CONCLUSIONS: Osteochondral
      vascularized MFT flaps provided a reliable means of lunate reconstruction in
      advanced Kienbock disease. This flap allowed resection of the proximal portion of
      the collapsed lunate and reconstruction with an anatomically analogous convex
      segment of vascularized cartilage-bearing bone. TYPE OF STUDY/LEVEL OF EVIDENCE:
      Therapeutic IV.

PMID- 24855961
TI  - Stability enhanced polyelectrolyte-coated gold nanorod-photosensitizer complexes
      for high/low power density photodynamic therapy.
AB  - Photodynamic therapy (PDT) is a promising treatment modality for cancer and other
      malignant diseases, however safety and efficacy improvements are required before
      it reaches its full potential and wider clinical use. Herein, we investigated a
      highly efficient and safe photodynamic therapy procedure by developing a high/low
      power density photodynamic therapy mode (high/low PDT mode) using
      methoxypoly(ethylene glycol) thiol (mPEG-SH) modified gold nanorod (GNR)-AlPcS4
      photosensitizer complexes. mPEG-SH conjugated to the surface of simple
      polyelectrolyte-coated GNRs was verified using Fourier transform infrared
      spectroscopy; this improved stability, reduced cytotoxicity, and increased the
      encapsulation and loading efficiency of the nanoparticle dispersions. The GNR
      photosensitizer complexes were exposed to the high/low PDT mode (high light dose
      = 80 mW/cm(2) for 0.5 min; low light dose = 25 mW/cm(2) for 1.5 min), and a high
      PDT efficacy leads to approximately 90% tumor cell killing. Due to synergistic
      plasmonic photothermal properties of the complexes, the high/low PDT mode
      demonstrated improved efficacy over using single wavelength continuous laser
      irradiation. Additionally, no significant loss in viability was observed in cells
      exposed to free AlPcS4 photosensitizer under the same irradiation conditions.
      Consequently, free AlPcS4 released from GNRs prior to cellular entry did not
      contribute to cytotoxicity of normal cells or impose limitations on the use of
      the high power density laser. This high/low PDT mode may effectively lead to a
      safer and more efficient photodynamic therapy for superficial tumors.

PMID- 24855966
TI  - Antegrade joint-sparing intramedullary wiring for middle phalanx shaft fractures.
AB  - PURPOSE: To evaluate the outcome for surgical stabilization of middle phalanx
      shaft fractures with joint-sparing antegrade intramedullary K-wire fixation.
      METHODS: We treated 15 extra-articular transverse or short oblique shaft
      fractures of the middle phalanx in 13 patients. All fractures were treated with
      closed reduction internal fixation with antegrade joint-sparing intramedullary K
      wires. Patients had a minimum follow-up of 1 year (range, 1-10 y). We assessed
      the objective outcome at 6 months by calculating total active range of motion.
      RESULTS: All fractures healed. Based on the total active motion score at 6
      months, 10 digits showed excellent results, 3 digits were good, 1 was fair, and 1
      was poor. Among 3 patients with an associated flexor tendon injury, 2 had
      excellent outcomes and one had a poor outcome. For 2 patients with an associated
      extensor tendon injury, 1 had a good outcome and the other had a fair outcome.
      CONCLUSIONS: Antegrade intramedullary wiring for extra-articular transverse and
      short oblique shaft  fracture of middle phalanx is a simple, safe, inexpensive,
      and joint-sparing technique that provides enough fracture stability, even in
      cases of associated injuries, for early rehabilitation and functional recovery
      with the expectation of a good to excellent outcome. TYPE OF STUDY/LEVEL OF
      EVIDENCE: Therapeutic IV.

PMID- 24855967
TI  - The role of prophylactic ulnar nerve release during elbow contracture release.

PMID- 24855968
TI  - An alternative graft fixation technique for scaphoid nonunions treated with
      vascular bone grafting.
AB  - PURPOSE: To present our experience with vascularized bone grafting based on the
      1,2-intercompartmental supraretinacular artery for the management of established
      scaphoid nonunion and to investigate the efficacy of graft immobilization with a
      combination of Kirschner wires and transarticular external fixation. METHODS: A
      retrospective chart and radiographic review was conducted for patients with the
      diagnosis of scaphoid nonunion of the proximal pole or the waist treated with the
      1,2-intercompartmental supraretinacular artery-based vascularized graft and fixed
      with a combination of Kirschner wires and transarticular external fixation
      between 2007 and 2011. RESULTS: We observed 23 consecutive patients for a mean of
      34 +/- 4 months. All patients were males with mean age of 25 +/- 5 years. All
      patients had scaphoid nonunion and associated humpback deformity. The mean
      duration of nonunion was 7 +/- 1 months. All scaphoid nonunions united after the
      index procedure at a mean of 10 +/- 1 weeks. Two patients had avascular necrosis
      of the proximal pole based on the preoperative magnetic resonance imaging
      findings. After surgery, deformity correction was achieved in all patients, as
      recorded by the decrease in the lateral intrascaphoid angle and the increase in
      the dorsal scaphoid angle. At the last follow-up, no patients reported wrist
      pain. The mean Disabilities of the Arm, Shoulder, and Hand score improved
      significantly from 32 +/- 12 before the operation to 5 +/- 3 at the last
      postoperative visit. All patients showed statistically significant improvement in
      the range of motion and the grip strength of the involved wrist. CONCLUSIONS: The
      results of this study support the combined use of Kirschner wires and
      transarticular external fixation for fixation of a 1,2-intercompartmental
      supraretinacular artery-based vascular bone graft in the treatment of scaphoid
      nonunions. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 24855969
TI  - Pisiform excision for pisotriquetral instability and arthritis.
AB  - PURPOSE: To evaluate wrist strength and kinematics after pisiform excision and
      preservation of its soft tissue confluence for pisotriquetral instability and
      arthritis. METHODS: We evaluated 12 patients, (14 wrists) subjectively and
      objectively an average of 7.5 years after pisiform excision. Three additional
      patients were interviewed by phone. Subjective evaluation included inquiry about
      pain and satisfaction with the treatment. Objective testing included measuring
      wrist flexion and extension range of motion, grip strength, and static and
      dynamic flexion and ulnar deviation strengths of the operative hand compared with
      the nonsurgical normal hand. Four patients had concomitant ulnar nerve
      decompression at the wrist. RESULTS: All patients were satisfied with the
      outcome. Wrist flexion averaged 99% and wrist extension averaged 95% of the
      nonsurgical hand. Mean grip strength of the operative hand was 90% of the
      nonsurgical hand. Mean static flexion strength of the operative hand was 94% of
      the nonsurgical hand, whereas mean dynamic flexion strength was 113%. Mean static
      ulnar deviation strength of the operative hand was 87% of the nonsurgical hand.
      The mean dynamic ulnar deviation strength of the operative hand was 103% of the
      nonsurgical hand. CONCLUSIONS: Soft tissue confluence-preserving pisiform
      excision relieved pain and retained wrist motion and static and dynamic strength.
      Associated ulnar nerve compression was a confounding factor that may have
      affected outcomes. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 24855970
TI  - Reactive metabolite trapping screens and potential pitfalls: bioactivation of a
      homomorpholine and formation of an unstable thiazolidine adduct.
AB  - Successful early attrition of potential problematic compounds is of great
      importance in the pharmaceutical industry. The lead compound in a recent project
      targeting neuropathic pain was susceptible to metabolic bioactivation, which
      produced reactive metabolites and showed covalent binding to protein. Therefore,
      as a part of the backup series for this compound several structural modifications
      were explored to mediate the reactive metabolite and covalent binding risk. A
      homomorpholine containing series of compounds was identified without compromising
      potency. However, when these compounds were incubated with human liver microsomes
      in the presence of GSH, Cys-Gly adducts were identified, instead of intact GSH
      conjugates. This article examines the formation of the Cys-Gly adduct with AZX
      ([M+H]+ 486) as a representative compound for this series. The AZX-Cys-Gly-adduct
      ([M+H]+ 662) showed evidence of ring contraction by formation of a thiazolidine
      glycine and was additionally shown to be unstable. During its isolation for
      structural characterization by 1H NMR spectroscopy, it was found to have
      decomposed to a product with [M+H]+ 446. The characterization and identification
      of this labile GSH-derived adduct using LC-MS/MS and 1H NMR are described, along
      with observations around stability. In addition, various structurally related
      trapping reagents were employed in an attempt to further investigate the reaction
      mechanism along with a methoxylamine trapping experiment to confirm the structure
      of the postulated reactive intermediate.

PMID- 24855971
TI  - Operational mechanism of conjugated polyelectrolytes.
AB  - Conjugated polyelectrolytes (CPEs) are versatile materials used in a range of
      organic optoelectronic applications. Because of their ionic/electronic nature,
      characterizing these materials is nontrivial, and their operational mechanism is
      not fully understood. In this work we use a methodology that combines constant
      voltage-driven current-density transient measurements with fast current vs
      voltage scans to allow decoupling of ionic and electronic phenomena. This
      technique is applied to diodes prepared with cationic CPEs having different
      charge-compensating anions. Our results indicate that the operational mechanism
      of these devices is governed by electrochemical doping of the CPE. On the basis
      of the notion that the saturated depletion layer for the anions consists of the
      same pi-conjugated backbone material, we discern how the extent and speed of
      formation of the doped region depend on the anion structure. Apart from
      addressing fundamental transport questions, this work provides a tool for future
      characterization of different CPEs and other similar systems. 

PMID- 24855972
TI  - Relationship between augmentation index and acute ischemic stroke subtype.
AB  - The aim of the present study was to explore the relationship between augmentation
      index (AIx) and vascular risk factors according to stroke subtypes. Patients were
      eligible for this study if they experienced their first ischemic stroke within
      the preceding 7 days and were 45 years of age or older. AIx was measured by
      applanation tonometry (SphygmoCor, AtCor Medical, Sydney, Australia) and ischemic
      stroke was classified according to the Trial of Org 10172 in the Acute Stroke
      Treatment (TOAST) classification system. A total of 189 patients were enrolled.
      The most frequent stroke subtype was lacune (76, 40.2%), followed by stroke of
      undetermined etiology, negative work-up (SUDn) (59, 31.2%), large artery
      atherosclerosis (LAA) (31, 16.4%), and cardioembolism (23, 12.2%). While there
      were no significant differences among the groups for hemodynamic indices, AIx at
      75 beats per minute (AIx@75) was higher in lacune subtype (29.6%) than SUDn
      (28.4%), LAA (26.6%), and cardioembolism (24.8%) (p=0.064). The AIx@75 was
      significantly related to age (r=0.189), sex (r=0.252), peripheral systolic blood
      pressure (SBP) (r=0.189), peripheral diastolic blood pressure (DBP) (r=0.191),
      and peripheral mean arterial pressure (MAP) (r=0.327). Multiple linear regression
      analysis revealed that age, sex, peripheral SBP, peripheral DBP and peripheral
      MAP were significant (p<0.002). This study showed that arterial stiffness is
      increased in acute lacunar infarction. Considering the pathogenesis of lacunar
      infarction and the potential interconnected causes of arterial stiffness, our
      findings indicate that increased arterial stiffness in acute lacunar infarction
      may be related to the pathogenesis of lacunar infarction.

PMID- 24855973
TI  - Management of patent ductus arteriosus in premature babies: the art and the
      sciences.

PMID- 24855975
TI  - Effects of hypoxia on biofilms and subsequently larval settlement of benthic
      invertebrates.
AB  - Biofilms on submerged surfaces are important in determining larval settlement of
      most marine benthic invertebrates. We investigated if exposure of biofilms to
      hypoxia would alter the larval settlement pattern and result in a shift in
      benthic invertebrate community structure in the field. Biofilms were first
      exposed to hypoxia or normoxia in laboratory microcosms for 7 days, and then
      deployed in the field for another 7 days to allow for larval settlement and
      recruitment to occur. Using terminal-restriction fragment length polymorphism of
      the 16S rRNA gene, this study showed that hypoxia altered the biofilm bacterial
      community composition, and the difference between the hypoxic and normoxic
      treatments increased with the time of exposure period. This study also
      demonstrated significantly different benthic invertebrate community structures as
      a result of biofilm exposure to hypoxia and that the hypoxic and normoxic
      treatments were dominated by Hydroides sp. and Folliculina sp., respectively.

PMID- 24855976
TI  - Large-scale oil spill simulation using the lattice Boltzmann method, validation
      on the Lebanon oil spill case.
AB  - This paper tests the adequacy of using the lattice Boltzmann method in large
      scale oil spill modelling, such as the Lebanon oil spill. Several numerical
      experiments were performed in order to select the most appropriate lattice and to
      decide between the single- and two-relaxation time models. Large-scale oil spills
      require simulations with short computational times. In order to speed up the
      computation and preserve adequate accuracy of the model, five different flux
      limiting interpolation techniques were compared and evaluated. The model was
      validated on the Lebanon oil spill with regard to the oil-slick position and
      concentrations in the sea, and the beaching area on the coast. Good agreement
      with satellite images of the slick and field data on beaching was achieved. The
      main advantages of the applied method are the capability of simulating very low
      oil concentrations and computational times that are by an order of magnitude
      shorter compared to similar models. 

PMID- 24855974
TI  - Mean platelet volume and ischemia modified albumin levels in cord blood of
      infants of diabetic mothers.
AB  - BACKGROUND: Gestational diabetes mellitus (GDM) is a risk for the health of both
      the pregnant women and her infant. Its unfavorable effects start in utero and
      continue after birth. It is known that GDM increases oxidative stress and
      decreases antioxidant enzyme activities. In this study we aimed to investigate
      cord blood mean platelet volume (MPV) and ischemia-modified albumin (IMA) levels
      of infants of diabetic mothers (IDM). METHODS: Twenty-nine pregnant women with
      GDM between 37 and 41 gestational weeks who gave birth by spontaneous vaginal
      delivery were enrolled as study participants together with 20 healthy pregnant
      women as a control group. Weight, length, and head circumference of babies were
      measured by the same standard tape immediately after birth. Five milliliters of
      umbilical venous blood were obtained to study MPV and IMA levels. RESULTS: There
      was statistically significant difference in levels of MPV (p = 0.037) and IMA (p
      < 0.001) between groups. They increased in IDM compared with their healthy peers.
      CONCLUSION: Evaluation of MPV and IMA together is useful for representing the
      potential oxidative stress of IDM.

PMID- 24855977
TI  - Suspended sediment in tidal currents: an often-neglected pollutant that
      aggravates mangrove degradation.
AB  - In this study, the influence of sediments deposited on the leaves of different
      mangrove species due to tidal movements on photosynthetic characteristics and
      chlorophyll fluorescence of the species was explored. The degree of accelerated
      degradation among different mangrove species was also obtained. Results show that
      the leaves of mangrove species have varying degrees of sediment deposition.
      Sediment deposition leads to photosynthetic reduction and physiological stress
      among Kandelia candel, Aegiceras corniculatum, and Avicennia marina in the
      Quanzhou Bay. Thus, the deposition of suspended sediments from tidal currents is
      an important environmental factor that accelerates the degradation of some
      mangrove species. 

PMID- 24855978
TI  - Human health risk of polycyclic aromatic hydrocarbons from consumption of blood
      cockle and exposure to contaminated sediments and water along the Klang Strait,
      Malaysia.
AB  - The concentration of carcinogenic poly aromatic hydrocarbons (c-PAHs) present in
      water and sediment of Klang Strait as well as in the edible tissue of blood
      cockle (Anadara granosa) was investigated. The human health risk of c-PAHs was
      assessed in accordance with the standards of the United States Environmental
      Protection Agency (US EPA). The cancer risks of c-PAHs to human are expected to
      occur through the consumption of blood cockles or via gastrointestinal exposure
      to polluted sediments and water in Kalng Strait. The non-carcinogenic risks that
      are associated with multiple pathways based on ingestion rate and contact rates
      with water were higher than the US EPA safe level at almost all stations, but the
      non-carcinogenic risks for eating blood cockle was below the level of US EPA
      concern. A high correlation between concentrations of c-PAHs in different
      matrices showed that the bioaccumulation of c-PAHs by blood cockles could be
      regarded as a potential health hazard for the consumers. 

PMID- 24855979
TI  - Geriatric depression and its relation with cognitive impairment and dementia.
AB  - Different subtypes of depressive syndromes exist in late life; many of them have
      cognitive impairment and sometimes it is difficult to differentiate them from
      dementia. This research aimed to investigate subtypes of geriatric depression
      associated with cognitive impairment, searched for differential variables and
      tried to propose a study model. A hundred and eighteen depressive patients and
      forty normal subjects matched by age and educational level were evaluated with an
      extensive neuropsychological battery, scales to evaluate neuropsychiatric
      symptoms and daily life activities (DLA). Depressive patients were classified in
      groups by SCAN 2.1: Major Depression Disorder (MDD) (n: 31), Dysthymia Disorder
      (DD) (n: 31), Subsyndromal Depression Disorder (SSD) (n: 29), Depression due to
      Dementia (n: 27) (DdD). Neuropsychological significant differences (p<0.05) were
      observed between depressive groups, demonstrating distinctive cognitive profiles.
      Moreover, significant differences (p<0.05) were found in DLA between DdD vs all
      groups and MDD vs controls and vs SSD. Age of onset varied in the different
      subtypes of depression. Beck Depression Inventory (BDI) and Mini Mental State
      Examination (MMSE) were significant variables that helped to differentiate
      depressive groups. Significant correlations between BDI and Neuropsychological
      tests were found in MDD and DD groups. Depressive symptoms and its relation with
      neuropsychological variables, MMSE, cognitive profiles, DLA and age of onset of
      depression should be taken into consideration for the study of subtypes of
      geriatric depression. 

PMID- 24855981
TI  - Quantification and reliability of center of pressure movement during balance
      tasks of varying difficulty.
AB  - Postural control is often assessed by quantifying the magnitude of the center of
      pressure (COP) movement. However, these measures usually focus on the gross
      amount of movement and ignore the temporal structure of the COP signal. A novel
      non-linear analysis technique was recently developed to characterize the temporal
      structure of the COP signal with an output termed the entropic half-life
      [E(1/2)]. The E(1/2) reflects how much of the previous postural position is used
      to determine the current postural control strategy (memory effect). The purpose
      of this study was to quantify the E(1/2) and four COP movement magnitude
      measurements (medio-lateral and anterior-posterior excursion, path length, 95%
      ellipse area) for balance tasks increasing in sensory difficulty, as well as the
      test-retest reliability of each measure. Twenty-seven healthy young adults
      completed single limb stance tasks varying in sensory difficulty (rigid surface
      eyes open, rigid surface eyes closed, foam surface eyes open) on two separate
      occasions. Relative reliability was assessed using an intraclass correlation
      coefficient (ICC3,3). Absolute reliability was assessed using the standard error
      of the measurement (SEM) and the sensitivity of the measurement to true changes
      was assessed using the minimal detectable change (MDC95). The E(1/2) was found to
      have excellent reliability for all tasks tested (ICC range 0.82-0.91, SEM range
      3.5-14.1 mm, MCD95 range 9.7-39.2 mm). The high reliability of the E(1/2) was
      comparable to that of movement magnitude measurements. This may be used in order
      to better understand the underlying motor control system.

PMID- 24855983
TI  - Development and enterprise-wide clinical implementation of an enhanced multimedia
      radiology reporting system.

PMID- 24855984
TI  - The advantages, disadvantages, and policies for part-time radiologists: report of
      the ACR Commission on Human Resources.
AB  - The employment of part-time radiologists (PTRs) has both advantages and
      disadvantages in various practice settings. The authors examine the pros and cons
      of PTRs and review the literature regarding PTRs both within and outside the
      specialty of radiology. The complexity of this issue is manifested in our
      inability to reach consensus on many policy issues for PTRs. Nevertheless, this
      article should be helpful in offering an objective, nonbiased background to
      initiating a discussion on employing PTRs in various radiology practices.

PMID- 24855987
TI  - Ester groups as carriers of antivirally active tricyclic analogue of acyclovir in
      prodrugs designing: synthesis, lipophilicity--comparative statistical study of
      the chromatographic and theoretical methods, validation of the HPLC method.
AB  - Knowledge of the lipophilicity of candidate compounds for prodrugs may predict
      their predetermined course/effect in the body. Acyclovir (ACV) belongs to a class
      of drugs with low bioavailability. Its tricyclic analogues, the derivatives of
      3,9-dihydro-3-[(2-hydroxyethoxy)methyl]-9-oxo-5H-imidazo[1,2-a]purine (TACV)
      exhibit similar antiviral activities and are more lipophilic as compared with
      acyclovir itself. In the search for new antiviral prodrugs 6-(4- methoxyphenyl)
      tricyclic compound (6-(4-MeOPh)-TACV) was modified by esterification of a
      hydroxyl group in the aliphatic chain. Selected esters (acetyl, isobutyryl,
      pivaloyl, ethoxycarbonyl and nicotinoyl) were synthesized and their lipophilicity
      was determined by the HPLC-RP method. The study compared the log kw calculated
      from the linear and quadratic equations and proved the correctness of the
      application of the linear relationship log k as a function of the concentration
      of ACN in the mobile phase (30-60%). Statistical analyses of the comparative
      values of log kw and clogP were carried out using computational methods. It was
      proved that the AC logP algorithm can be useful for the analysis of these
      compounds, which can have a statistically justified application in the assessment
      of the quantitative structure- activity relationship (QSAR). The lipophilicity
      determined by the HPLC method appears as follows: 6-(4-MeOPh)-TACV < Ac- < Nic- <
      Etc- < iBut- < Piv- (log kw = 0.65-2.26). Finally, the HPLC-RP method was
      developed and validated for simultaneous determination of synthesized esters. 

PMID- 24855989
TI  - Therapeutical approaches under investigation for treatment of Chagas disease.
AB  - INTRODUCTION: A century after its discovery, American trypanosomiasis or Chagas
      disease remains a serious health problem in Latin America, where it affects
      around 7 - 8 million people. The prevalence of Chagas disease in the poorer parts
      of the world has meant that it has largely been neglected with limited progress
      that made in identifying new drugs for the treatment. The nitroheterocyclic drugs
      nifurtimox and benznidazole are first-line drugs available for Chagas disease
      with limitations that include variable efficacy, long treatment courses and
      toxicity. AREAS COVERED: This review focuses on different therapeutic strategies
      that have been used for the discovery of new treatments for Chagas disease. These
      include combination chemotherapy, drug repositioning, re-dosing regimens for
      current drugs and the identification of new drugs with specified target profiles.
      EXPERT OPINION: There are currently several reasons for a more optimistic view
      about chemotherapy with Chagas disease. However, despite some progress being made
      in preclinical studies, there is yet to be an ideal drug or formulation for human
      treatment. One major drawback in the evaluation of potential Chagas disease
      therapeutics is the lack of tools available to perform the said evaluation.
      Indeed, there is a great need to discover a better biomarker that could determine
      the efficacy of potential chemotherapeutics in treated patients.

PMID- 24855985
TI  - Maternal hepatitis B and infant infection among pregnant women living with HIV in
      South Africa.
AB  - INTRODUCTION: Globally, hepatitis B virus (HBV) infection is the leading cause of
      liver-related mortality. Newborn vaccination, maternal antiviral therapy and
      administering hepatitis B immune globulin shortly after birth can greatly reduce
      the risk of perinatal and infant infection. However, evidence-based policy
      regarding these interventions in Africa is hampered by gaps in knowledge of HBV
      epidemiology. We describe maternal chronic hepatitis B (CHB) prevalence and
      infant infection during the first year of life within a cohort of women living
      with HIV. METHODS: We recruited and prospectively followed pregnant women living
      with HIV and their infants from prenatal clinics in an urban area of South
      Africa. Hepatitis B surface antigen, anti-hepatitis B surface antibodies and HBV
      DNA were assessed in all women. Hepatitis B testing was also performed at 6 and
      52 weeks for all infants born to mothers with either positive surface antigen or
      detectable HBV DNA. RESULTS: We enrolled 189 women with a median age of 29 years
      and median CD4 count of 348 cells/mm(3). Fourteen had a positive surface antigen
      (7.4%), of which six were positive for "e" antigen. An additional three had
      detectable HBV DNA without positive surface antigen. One infant developed CHB and
      three others had evidence of transmission based on positive HBV DNA assays. HBV
      vaccinations were delivered at six weeks of life to all infants. CONCLUSIONS: Our
      findings highlight the risk of peripartum HBV transmission in this setting.
      Approaches to reducing this transmission should be considered.

PMID- 24855990
TI  - Fostering person-centered care among nursing students: creative pedagogical
      approaches to developing personal knowing.
AB  - Person-centered care (PCC) is grounded in principles of respect, autonomy, and
      empowerment and requires the development of interpersonal relationships. For
      nursing students to engage in PCC, they need to intentionally develop personal
      knowing, which is an essential attribute of therapeutic relationships. Developing
      personal knowing, as well as professional knowledge, positions students to enact
      PCC in their practice. Faculty members play a vital role in fostering the
      development of personal knowing by creating opportunities for students in which
      genuine and respectful dialogue, reflection, self-awareness, and critical
      thinking can take place. This article explores several creative approaches
      faculty have used to actualize these qualities in their teaching-learning
      encounters with nursing students at various stages of their students'
      professional development. These approaches offer experiential teaching-learning
      opportunities that foster the development of personal knowing, as well as
      constructive and respectful relationships between faculty and students, therefore
      laying the groundwork for PCC in practice settings.

PMID- 24855991
TI  - First-time NCLEX-RN pass rate: measure of program quality or something else?
AB  - The first-time NCLEX-RN((r)) pass rate is considered by many to be the primary,
      if not sole, indicator of the quality of prelicensure nursing education programs.
      Used by state boards of nursing, educational program accreditors, and nursing
      faculty, the first-time NCLEX-RN pass rate influences important decisions about
      overall program quality, admission and progression policies, curricula, and
      teaching and learning practices. In this article, the authors call for a
      professional dialogue about the use of first-time pass rate (F-TPR) as an
      indicator of program quality, offer alternative methods for using the F-TPR as
      one measure of program quality, and suggest further research. One program's
      experience with low F-TPRs is offered as an exemplar of the unintended negative
      consequences that occur when the F-TPR is used as a sole criterion by a state
      board of nursing in judging a program's quality.

PMID- 24855992
TI  - Academic progression models in nursing: design decisions faced by administrators
      in four case studies.
AB  - Although nursing education pathways have expanded access to the profession,
      fragmentation accompanying these entry points has created uncertainty among
      students about the desired end point, questionable efficiency and effectiveness
      of reaching career goals, and unclear merging mechanisms to enable seamless,
      linear progression. In response to these challenges and in anticipation of
      greater demands on nurses due to health reform, the Institute of Medicine (IOM)
      examined the capacity of the nursing workforce and proposed a transformative
      blueprint for change that relies on an education system to promote seamless
      academic progression. Despite support for this recommendation, little research
      exists regarding the best way to achieve the IOM's vision. This study examined
      the most promising practices in design and implementation of alternative pathways
      for academic progression in nursing. Four case studies are presented that explore
      the challenges of designing alternative pathways and identify performance
      measures to assist with developing such programs.

PMID- 24855993
TI  - Improving pandemic H5N1 influenza vaccines by combining different vaccine
      platforms.
AB  - A variety of platforms are being explored for the development of vaccines for
      pandemic influenza. Observations that traditional inactivated subvirion vaccines
      and live-attenuated vaccines against H5 and some H7 influenza viruses were poorly
      immunogenic spurred efforts to evaluate new approaches, including whole virus
      vaccines, higher doses of antigen, addition of adjuvants and combinations of
      different vaccine modalities in heterologous prime-boost regimens to potentiate
      immune responses. Results from clinical trials of prime-boost regimens have been
      very promising. Further studies are needed to determine optimal combinations of
      platforms, intervals between doses of vaccines and the logistics of deployment in
      pre-pandemic and early pandemic settings. 

PMID- 24855994
TI  - The relationship between electrical auditory brainstem responses and perceptual
      thresholds in Digisonic(r) SP cochlear implant users.
AB  - Determining the electrical stimulation levels is often a difficult and time
      consuming task because they are normally determined behaviorally - a particular
      challenge when dealing with pediatric patients. The evoked stapedius reflex
      threshold and the evoked compound action potential have already been shown to
      provide reasonable estimates of the C- and T-levels, although these estimates
      tend to overestimate the C- and T-levels. The aim of this study was to
      investigate whether the evoked auditory brainstem response (eABR) can also be
      used to reliably estimate a patient's C- and T-levels. The correlation between
      eABR detection thresholds and behaviorally measured perceptual thresholds was
      statistically significant (r = 0.71; P < 0.001). In addition, eABR Wave-V
      amplitude increased with increasing stimulation level for the three loudness
      levels tested. These results show that the eABR detection threshold can be used
      to estimate a patient's T-levels. In addition, Wave-V amplitude could provide a
      method for estimating C-levels in the future. The eABR objective measure may
      provide a useful cochlear implant fitting method - particularly for pediatric
      patients. 

PMID- 24855995
TI  - Asymmetric patterns of CSF flow in the spinal subarachnoid cisterns in patients
      with syringomyelia: clinical implications.

PMID- 24855996
TI  - Hypoxia promotes nucleus pulposus phenotype in 3D scaffolds in vitro and in vivo:
      laboratory investigation.
AB  - OBJECT: The role of oxygen in disc metabolism remains a matter of debate. Whether
      the effect of hypoxic priming on the nucleus pulposus phenotype can be maintained
      in vivo is not clear. The goal of the present study was to test the hypothesis
      that priming in a low oxygen tension in vitro could promote a nucleus pulposus
      phenotype in vivo. METHODS: Bovine nucleus pulposus cells were seeded in 3D
      scaffolds and subjected to varying oxygen tensions (2% and 20%) for 3 weeks. The
      constructs were then implanted subcutaneously for 8 weeks. Changes in the
      extracellular matrix were evaluated using quantitative real-time reverse
      transcriptase polymerase chain reaction, glycosaminoglycan (GAG) assay, DNA
      assay, collagen quantification, and histological and immunohistological analyses.
      RESULTS: Hypoxia resulted in greater production of sulfated glycosaminoglycan and
      higher levels of gene expression for collagen Type II, aggrecan, and SOX-9.
      Furthermore, after hypoxic priming, the subcutaneously implanted constructs
      maintained the nucleus pulposus phenotype, which was indicated by a significantly
      higher amount of glycosaminoglycan and collagen Type II. CONCLUSIONS: Hypoxia
      enhanced the nucleus pulposus phenotype under experimental conditions both in
      vitro and in vivo. When used in combination with appropriate scaffold material,
      nucleus pulposus cells could be regenerated for tissue-engineering applications.

PMID- 24855998
TI  - Regio- and stereoselective synthesis of ferrocene-containing beta-iodoallylic
      esters and ethers from the iodofunctionalization of ferrocenylallene with
      carboxylic acids, phenols, and alcohols.
AB  - The iodofunctionalization of ferrocenylallene with carboxylic acids, phenols, and
      alcohols is described. The reaction proceeds smoothly in the presence of molecule
      iodine as a halonium promoter and using various carboxylic acids, phenols, and
      alcohols as nucleophiles to give the corresponding ferrocene-containing beta
      iodoallylic ester and ether products in moderate to high yields and with high
      regio- and stereoselectivities. It can be envisaged that the regio- and
      stereoselectivity of this reaction may be controlled by the steric effect of the
      bulky ferrocene group. The presence of the C-I bond in the corresponding products
      makes these molecules highly attractive from a synthetic point of view, as it
      provides an opportunity for further transformations. Thus, palladium-catalyzed
      Heck coupling, Suzuki coupling, Sonogashira coupling, and copper-catalyzed click
      reactions were carried out successfully. 

PMID- 24855997
TI  - Electrophysiological evidence of functional improvement in the corticospinal
      tract after laminoplasty in patients with cervical compressive myelopathy:
      clinical article.
AB  - OBJECT: Cervical laminoplasty is a surgical procedure for cervical compressive
      myelopathy (CCM), and satisfactory outcomes have been reported. However, few
      reports have examined the pathophysiology of improvements in spinal cord
      function. The aim of this study was to investigate the variation in central motor
      conduction time (CMCT) before and after cervical laminoplasty in patients with
      CCM. METHODS: Motor evoked potentials (MEPs) following transcranial magnetic
      stimulation and compound muscle action potentials (CMAPs) and F-waves following
      electrical stimulation of the ulnar and tibial nerves at the wrist and ankle were
      measured from the abductor digiti minimi muscle (ADM) and abductor hallucis
      muscle (AH) in 42 patients with CCM before and 1 year after cervical
      laminoplasty. The peripheral conduction time (PCT) was calculated as follows:
      (latency of CMAPs + latency of F-waves - 1)/2. The CMCT was calculated by
      subtracting the PCT from the onset latency of the MEPs. The CMCT recovery ratio
      was defined and calculated as the ratio of CMCT values 1 year after surgery to
      those before surgery. The CMCT data were analyzed as longer or shorter CMCT
      between the patients' right and left ADMs and AHs. The Japanese Orthopaedic
      Association (JOA) score for cervical myelopathy was obtained as a clinical
      outcome before and 1 year after surgery. The recovery rate (RR) 1 year after
      surgery was calculated using the following formula: (postoperative JOA score 1
      year after surgery - preoperative JOA score)/(17 - preoperative JOA score) * 100.
      Correlations among CMCT parameters, patient age, JOA score, and RR were
      determined. RESULTS: The longer and shorter CMCTs from the ADM (longer, p =
      0.000; shorter, p = 0.008) and the longer CMCT from the AH (longer, p = 0.000)
      before surgery decreased significantly 1 year after surgery; the shorter CMCT
      from the AH did not significantly differ (shorter, p = 0.078). The mean JOA score
      before surgery was 10.1 +/- 3.0 and improved significantly to 12.9 +/- 2.7 at 1
      year after surgery (p = 0.000). The mean CMCT recovery ratio and RR were 0.91 +/-
      0.18 and 0.43 +/- 0.27, respectively. The longer/shorter CMCT parameters in the
      ADM and AH before or 1 year after surgery correlated significantly with the JOA
      score both before and 1 year after surgery. The CMCT recovery ratio from the
      longer CMCT in the ADM correlated significantly with the RR (r = - 3090, p =
      0.011). There were no significant correlations between age and any CMCT
      parameters or CMCT recovery ratios. CONCLUSIONS: These results suggest that
      cervical laminoplasty improves corticospinal tract function 1 year after surgery,
      which may be one of the reasons for the JOA score improvements in patients with
      CCM. The degree of improvement in corticospinal tract function did not correlate
      with patient age in this case series. The results demonstrated quantitative
      evidence of the pathophysiology of functional recovery in the corticospinal tract
      following cervical laminoplasty in patients with CCM.

PMID- 24855999
TI  - A possible mechanism for redox control of human neuroglobin activity.
AB  - Neuroglobin (Ngb) promotes neuron survival under hypoxic/ischemic conditions. In
      vivo and in vitro assays provide evidence for redox-regulated functioning of Ngb.
      On the basis of X-ray crystal structures and our MD simulations, a mechanism for
      redox control of human Ngb (hNgb) activity via the influence of the CD loop on
      the active site is proposed. We provide evidence that the CD loop undergoes a
      strand-to-helix transition when the external environment becomes sufficiently
      oxidizing, and that this CD loop conformational transition causes critical
      restructuring of the active site. We postulate that the strand-to-helix mechanics
      of the CD loop allows hNgb to utilize the lability of Cys46/Cys55 disulfide
      bonding and of the Tyr44/His64/heme propionate interaction network for redox
      controlled functioning of hNgb. 

PMID- 24856000
TI  - Bifunctional N-heterocyclic carbene-catalyzed highly enantioselective synthesis
      of spirocyclic oxindolo-beta-lactams.
AB  - The N-heterocyclic carbene-catalyzed Staudinger reaction of ketenes with isatin
      derived ketimines was investigated. The bifunctional NHCs with a free hydroxyl
      group were demonstrated as efficient catalysts for the reaction, giving the
      corresponding spirocyclic oxindolo-beta-lactams in high yields with excellent
      diastereo- and enantioselectivities. 

PMID- 24856001
TI  - Zika virus, French polynesia, South pacific, 2013.

PMID- 24856002
TI  - Sequence-selective molecular recognition of the C-terminal CaaX-boxes of Rheb and
      related Ras-proteins by synthetic receptors.
AB  - Constitutive activation of Ras-proteins plays an important role in the
      development of aggressive colorectal carcinomas and several other types of
      cancer. Despite some progress in recent years in the case of K-Ras4B, until now
      not a single small molecule inhibitor has been identified that binds efficiently
      to Rheb and interrupts the protein-protein interactions with mTOR. We describe
      here a complementary approach that aims at inhibiting membrane insertion of Rheb
      and related Ras proteins by masking the crucial C-terminal CaaX-box with
      peptidomimetic receptors identified in combinatorial solid-phase libraries. 

PMID- 24856003
TI  - Ultrarapid detection of pathogenic bacteria using a 3D immunomagnetic flow assay.
AB  - We developed a novel 3D immunomagnetic flow assay for the rapid detection of
      pathogenic bacteria in a large-volume food sample. Antibody-functionalized
      magnetic nanoparticle clusters (AbMNCs) were magnetically immobilized on the
      surfaces of a 3D-printed cylindrical microchannel. The injection of a Salmonella
      spiked sample solution into the microchannel produced instant binding between the
      AbMNCs and the Salmonella bacteria due to their efficient collisions. Nearly
      perfect capture of the AbMNCs and AbMNCs-Salmonella complexes was achieved under
      a high flow rate by stacking permanent magnets with spacers inside the
      cylindrical separator to maximize the magnetic force. The concentration of the
      bacteria in solution was determined using ATP luminescence measurements. The
      detection limit was better than 10 cfu/mL, and the overall assay time, including
      the binding, rinsing, and detection steps for a 10 mL sample took less than 3
      min. To our knowledge, the 3D immunomagnetic flow assay described here provides
      the fastest high-sensitivity, high-capacity method for the detection of
      pathogenic bacteria. 

PMID- 24856004
TI  - Iatrogenic meningitis caused by Neisseria sicca/subflava after intrathecal
      contrast injection, Australia.
AB  - We report a case of invasive Neisseria sicca/subflava meningitis after a spinal
      injection procedure during which a face mask was not worn by the proceduralist.
      The report highlights the importance of awareness of, and adherence to,
      guidelines for protective face mask use during procedures that require sterile
      conditions. 

PMID- 24856005
TI  - Rotation flap lobuloplasty: technique and experience with 24 partially torn
      earlobes.
AB  - Multiple techniques exist for the repair of partial earlobe deformities. The
      procedures in use vary from minimal interventions involving marginal excision and
      closure, to cartilage grafting to prevent recurrence. A prospective study was
      conducted of 24 partial earlobe deformity repair procedures using the technique
      devised by the authors, involving a rotation flap for reduction of the defect
      size. Aesthetic outcomes and postoperative complications were assessed on the
      basis of clinical findings and photographic documentation. Sixteen female
      patients underwent the procedure of rotation flap repair of partial earlobe
      deformities (24 earlobes) between July 2011 and August 2012. The average age of
      the patients was 44 years, and the average length of follow-up was 14 months.
      Patient satisfaction was good. Adequate functional and cosmetic results were
      achieved in the first 2 weeks for 19 earlobes (79%). Good results were seen
      during 1 year of follow-up. The rotation flap technique appears to offer an
      effective method for partial earlobe defect repair, and thus provides another
      option for the management of partial earlobe defects.

PMID- 24856009
TI  - Nursing in the UK: where next?

PMID- 24856006
TI  - Comparative effects of plant oils on the cerebral hemorrhage in stroke-prone
      spontaneously hypertensive rats.
AB  - OBJECTIVES: Since oils and fats can induce metabolic syndrome, leading to
      cardiovascular and cerebrovascular diseases, the present study was performed to
      find out whether the plant oils affect the cerebral hemorrhage in stroke-prone
      spontaneously hypertensive (SHR-SP) rats. METHODS: From 47 days of age, male SHR
      SP rats were given drinking water containing 1% NaCl to induce hypertension, and
      simultaneously fed semi-purified diets containing 10% perilla oil, canola oil, or
      shortening. The onset time of convulsion following cerebral hemorrhage was
      recorded, and the areas of hemorrhage and infarction were analyzed in the stroke
      brains. RESULTS: In comparison with 58-day survival of SHR-SP rats during feeding
      NaCl alone, perilla oil extended the survival time to 68.5 days, whereas canola
      oil shortened it to 45.7 days. Feeding perilla oil greatly reduced the total
      volume of cerebral hemorrhage from 17.27% in the control group to 4.53%, while
      shortening increased the lesions to 21.23%. In a microscopic analysis, perilla
      oil also markedly decreased the hemorrhagic and infarction lesions to 1/10 of
      those in control rats, in contrast to an exacerbating effect of shortening. In
      blood analyses, perilla oil reduced blood total cholesterol and low-density
      lipoproteins which were increased in SHR-SP, but canola oil further increased
      them and markedly lowered platelet counts. DISCUSSION: Perilla oil delayed and
      attenuated cerebral hemorrhage by improving hyperlipidemia in hypertensive stroke
      animals, in contrast to the aggravating potential of canola oil and shortening.
      It is suggested that perilla oil should be the first choice oil for improving
      metabolic syndrome in hypertensive persons at risk of hemorrhagic stroke.

PMID- 24856010
TI  - Seizing the opportunity to rethink renal research.

PMID- 24856008
TI  - [Chordoma].
AB  - PURPOSES: To review in the literature, all the epidemiological, clinical,
      radiological, histological and therapeutic data regarding chordomas as well as
      various notochordal entities: ecchordosis physaliphora, intradural and
      intraparenchymatous chordomas, benign notochordal cell tumors, parachordomas and
      extra-axial chordomas. To identify different types of chordomas, including
      familial forms, associations with tuberous sclerosis, Ollier's disease and
      Maffucci's syndrome, forms with metastasis and seeding. To assess the recent data
      regarding molecular biology and progress in targeted therapy. To compare the
      different types of radiotherapy, especially protontherapy and their therapeutic
      effects. To review the largest series of chordomas in their different
      localizations (skull base, sacrum and mobile spine) from the literature.
      MATERIALS: The series of 136 chordomas treated and followed up over 20 years
      (1972-2012) in the department of neurosurgery at Lariboisiere hospital is
      reviewed. It includes: 58 chordomas of the skull base, 47 of the craniocervical
      junction, 23 of the cervical spine and 8 from the lombosacral region. Similarly,
      31 chordomas in children (less than 18 years of age), observed in the departments
      of neurosurgery of les Enfants-Malades and Lariboisiere hospitals, are presented.
      They were observed between 1976 and 2010 and were located intracranially (n=22
      including 13 with cervical extension), 4 at the craniocervical junction level and
      5 in the cervical spine. METHODS: In the entire Lariboisiere series and in the
      different groups of localization, different parameters were analyzed: the delay
      of diagnosis, of follow-up, of occurrence of metastasis, recurrence and death,
      the number of primary patients and patients referred to us after progression or
      recurrence and the number of deaths, recurrences and metastases. The influence of
      the quality of resection (total, subtotal and partial) on the prognosis is also
      presented. Kaplan-Meier actuarial curves of overall survival and disease free
      survival were performed in the entire series, including the different groups of
      localization based on the following 4 parameters: age, primary and secondary
      patients, quality of resection and protontherapy. In the pediatric series, a
      similar analysis was carried-out but was limited by the small number of patients
      in the subgroups. RESULTS: In the Lariboisiere series, the mean delay of
      diagnosis is 10 months and the mean follow-up is 80 months in each group. The
      delay before recurrence, metastasis and death is always better for the skull base
      chordomas and worse for those of the craniocervical junction, which have similar
      results to those of the cervical spine. Similar figures were observed as regards
      the number of deaths, metastases and recurrences. Quality of resection is the
      major factor of prognosis with 20.5 % of deaths and 28 % of recurrences after
      total resection as compared to 52.5 % and 47.5 % after subtotal resection. This
      is still more obvious in the group of skull base chordomas. Adding protontherapy
      to a total resection can still improve the results but there is no change after
      subtotal resection. The actuarial curve of overall survival shows a clear cut in
      the slope with some chordomas having a fast evolution towards recurrence and
      death in less than 4 years and others having a long survival of sometimes more
      than 20 years. Also, age has no influence on the prognosis. In primary patients,
      disease free survival is better than in secondary patients but not in overall
      survival. Protontherapy only improves the overall survival in the entire series
      and in the skull base group. Total resection improves both the overall and
      disease free survival in each group. Finally, the adjunct of protontherapy after
      total resection is clearly demonstrated. In the pediatric series, the median
      follow-up is 5.7 years. Overall survival and disease free survival are
      respectively 63 % and 54.3 %. Factors of prognosis are the histological type
      (atypical forms), localization (worse for the cervical spine and better for the
      clivus) and again it will depend on the quality of resection. CONCLUSIONS: Many
      different pathologies derived from the notochord can be observed: some are
      remnants, some may be precursors of chordomas and some have similar features but
      are probably not genuine chordomas. To-day, immuno-histological studies should
      permit to differentiate them from real chordomas. Improving knowledge of
      molecular biology raises hopes for complementary treatments but to date the
      quality of surgical resection is still the main factor of prognosis.
      Complementary protontherapy seems useful, especially in skull base chordomas,
      which have better overall results than those of the craniocervical junction and
      of the cervical spine. However, we are still lacking an intrinsic marker of
      evolution to differentiate the slow growing chordomas with an indolent evolution
      from aggressive types leading rapidly to recurrence and death on which more
      aggressive treatments should be applied.

PMID- 24856011
TI  - MERS-CoV: address the knowledge gaps to move forward.

PMID- 24856013
TI  - Extracorporeal therapy for the smallest children.

PMID- 24856012
TI  - Renal replacement therapy: how can we contain the costs?

PMID- 24856014
TI  - Hydration in contrast-induced acute kidney injury.

PMID- 24856017
TI  - Raymond Vanholder: a titan of uraemic toxicity.

PMID- 24856018
TI  - Adding the doctor's voice to the global health agenda.

PMID- 24856019
TI  - What have economists ever done for global health?

PMID- 24856020
TI  - Access to controlled medicines for pain relief and anaesthesia in low-income
      countries.

PMID- 24856021
TI  - Investing in obstetric surgery and anaesthesia to close the gap in maternal
      mortality.

PMID- 24856022
TI  - Neglected tropical diseases in the post-2015 health agenda.

PMID- 24856023
TI  - Cervical cancer mortality in India.

PMID- 24856024
TI  - Cervical cancer mortality in India - Authors' reply.

PMID- 24856025
TI  - Assessing the French Alzheimer plan.

PMID- 24856026
TI  - Continuous renal replacement therapy in neonates and small infants: development
      and first-in-human use of a miniaturised machine (CARPEDIEM).
AB  - BACKGROUND: Peritoneal dialysis is the renal replacement therapy of choice for
      acute kidney injury in neonates, but in some cases is not feasible or effective.
      Continuous renal replacement therapy (CRRT) machines are used off label in
      infants smaller than 15 kg and are not designed specifically for small infants.
      We aimed to design and create a CRRT machine specifically for neonates and small
      infants. METHODS: We prospectively planned a 5-year project to conceive, design,
      and create a miniaturised Cardio-Renal Pediatric Dialysis Emergency Machine
      (CARPEDIEM), specifically for neonates and small infants. We created the new
      device and assessed it with in-vitro laboratory tests, completed its development
      to meet regulatory requirements, and obtained a licence for human use. Once
      approved, we used the machine to treat a critically ill neonate FINDINGS: The
      main characteristics of CARPEDIEM are the low priming volume of the circuit (less
      than 30 mL), miniaturised roller pumps, and accurate ultrafiltration control via
      calibrated scales with a precision of 1 g. In-vitro tests confirmed that both
      hardware and software met the specifications. We treated a 2.9 kg neonate with
      haemorrhagic shock, multiple organ dysfunction, and severe fluid overload for
      more than 400 h with the CARPEDIEM, using continuous venovenous haemofiltration,
      single-pass albumin dialysis, blood exchange, and plasma exchange. The patient's
      65% fluid overload, raised creatinine and bilirubin concentrations, and severe
      acidosis were all managed safely and effectively. Despite the severity of the
      illness, organ function was restored and the neonate survived and was discharged
      from hospital with only mild renal insufficiency that did not require renal
      replacement therapy. INTERPRETATION: The CARPEDIEM CRRT machine can be used to
      provide various treatment modalities and support for multiple organ dysfunction
      in neonates and small infants. The CARPEDIEM could reduce the range of
      indications for peritoneal dialysis, widen the range of indications for CRRT,
      make the use of CRRT less traumatic, and expand its use as supportive therapy
      even when complete renal replacement therapy is not indicated. FUNDING:
      Associazione Amici del Rene di Vicenza.

PMID- 24856027
TI  - Haemodynamic-guided fluid administration for the prevention of contrast-induced
      acute kidney injury: the POSEIDON randomised controlled trial.
AB  - BACKGROUND: The administration of intravenous fluid remains the cornerstone
      treatment for the prevention of contrast-induced acute kidney injury. However, no
      well-defined protocols exist to guide fluid administration in this treatment. We
      aimed to establish the efficacy of a new fluid protocol to prevent contrast
      induced acute kidney injury. METHODS: In this randomised, parallel-group,
      comparator-controlled, single-blind phase 3 trial, we assessed the efficacy of a
      new fluid protocol based on the left ventricular end-diastolic pressure for the
      prevention of contrast-induced acute kidney injury in patients undergoing cardiac
      catheterisation. The primary outcome was the occurrence of contrast-induced acute
      kidney injury, which was defined as a greater than 25% or greater than 0.5 mg/dL
      increase in serum creatinine concentration. Between Oct 10, 2010, and July 17,
      2012, 396 patients aged 18 years or older undergoing cardiac catheterisation with
      an estimated glomerular filtration rate of 60 mL/min per 1.73 m(2) or less and
      one or more of several risk factors (diabetes mellitus, history of congestive
      heart failure, hypertension, or age older than 75 years) were randomly allocated
      in a 1:1 ratio to left ventricular end-diastolic pressure-guided volume expansion
      (n=196) or the control group (n=200) who received a standard fluid administration
      protocol. Four computer-generated concealed randomisation schedules, each with
      permuted block sizes of 4, were used for randomisation, and participants were
      allocated to the next sequential randomisation number by sealed opaque envelopes.
      Patients and laboratory personnel were masked to treatment assignment, but the
      physicians who did the procedures were not masked. Both groups received
      intravenous 0.9% sodium chloride at 3 mL/kg for 1 h before cardiac
      catheterisation. Analyses were by intention to treat. Adverse events were
      assessed at 30 days and 6 months and all such events were classified by staff who
      were masked to treatment assignment. This trial is registered with
      ClinicalTrials.gov, number NCT01218828. FINDINGS: Contrast-induced acute kidney
      injury occurred less frequently in patients in the left ventricular end-diastolic
      pressure-guided group (6.7% [12/178]) than in the control group (16.3% [28/172];
      relative risk 0.41, 95% CI 0.22-0.79; p=0.005). Hydration treatment was
      terminated prematurely because of shortness of breath in three patients in each
      group. INTERPRETATION: Left ventricular end-diastolic pressure-guided fluid
      administration seems to be safe and effective in preventing contrast-induced
      acute kidney injury in patients undergoing cardiac catheterisation. FUNDING:
      Kaiser Permanente Southern California regional research committee grant.

PMID- 24856028
TI  - Epidemiology, contributors to, and clinical trials of mortality risk in chronic
      kidney failure.
AB  - Patients with chronic kidney failure--defined as a glomerular filtration rate
      persistently below 15 mL/min per 1.73 m(2)--have an unacceptably high mortality
      rate. In developing countries, mortality results primarily from an absence of
      access to renal replacement therapy. Additionally, cardiovascular and non
      cardiovascular mortality are several times higher in patients on dialysis or post
      renal transplantation than in the general population. Mortality of patients on
      renal replacement therapy is affected by a combination of socioeconomic factors,
      pre-existing medical disorders, renal replacement treatment modalities, and
      kidney failure itself. Characterisation of the key pathophysiological
      contributors to increased mortality and cardiorenal risk staging systems are
      needed for the rational design of clinical trials aimed at decreasing mortality.
      Policy changes to improve access to renal replacement therapy should be combined
      with research into low-cost renal replacement therapy and optimum clinical care,
      which should include multifaceted approaches simultaneously targeting several of
      the putative contributors to increased mortality.

PMID- 24856030
TI  - A painful swollen thigh in a diabetic patient: diabetic myonecrosis.

PMID- 24856031
TI  - Current Problems in Cardiology. Foreword.

PMID- 24856032
TI  - Assessment of coronary blood flow in the cardiac catheterization laboratory.
AB  - Coronary blood flow is tightly autoregulated but is subject to epicardial and
      microvascular obstruction, primarily owing to coronary atherosclerosis. Because
      coronary flow limitation underlies ischemic heart disease, an understanding of
      coronary physiology is paramount. Measurement of coronary blood flow, once
      relegated to the research laboratory is now easily performed in the cardiac
      catheterization laboratory. In particular, the measurement of fractional flow
      reserve has been extensively studied and is an important adjunct to clinical
      decision making. Measurement of coronary flow informs clinicians of prognosis,
      guides revascularization therapy, and forms the basis of ongoing research in
      treatment of complex myocardial disease processes. Newer methods of assessing
      coronary flow measurements are undergoing validation for clinical use and should
      further enhance our ability to assess the importance of coronary flow in clinical
      disease. 

PMID- 24856029
TI  - Rare inherited kidney diseases: challenges, opportunities, and perspectives.
AB  - At least 10% of adults and nearly all children who receive renal-replacement
      therapy have an inherited kidney disease. These patients rarely die when their
      disease progresses and can remain alive for many years because of advances in
      organ-replacement therapy. However, these disorders substantially decrease their
      quality of life and have a large effect on health-care systems. Since the kidneys
      regulate essential homoeostatic processes, inherited kidney disorders have
      multisystem complications, which add to the usual challenges for rare disorders.
      In this review, we discuss the nature of rare inherited kidney diseases, the
      challenges they pose, and opportunities from technological advances, which are
      well suited to target the kidney. Mechanistic insights from rare disorders are
      relevant for common disorders such as hypertension, kidney stones, cardiovascular
      disease, and progression of chronic kidney disease. 

PMID- 24856039
TI  - DynaCT imaging for intraprocedural evaluation of flow-diverting stent apposition
      during endovascular treatment of intracranial aneurysms.
AB  - The treatment of large, complex intracranial aneurysms is being increasingly
      performed using flow-diverting stents (FDS) such as the Pipeline Embolization
      Device (PED; ev3, Irvine, CA, USA). Malapposition of a FDS to the parent artery
      wall decreases the likelihood of aneurysm obliteration and increases the risk of
      both immediate and delayed complications. DynaCT scanning (Siemens Medical
      Solutions, Erlangen, Germany) is a novel imaging modality which uses a flat plane
      detector to generate CT images using the same C-arm employed for digital
      subtraction angiography. We present a 40-year-old woman with an unruptured, 11 mm
      cavernous internal carotid artery aneurysm who was treated with endovascular
      obliteration using a PED. Intraprocedural DynaCT scan performed after PED
      deployment demonstrated incomplete stent apposition to the parent vessel which
      could not be detected on digital subtraction angiography alone. Balloon
      angioplasty was performed to improve apposition of the stent to the vessel wall.
      There were no procedural or clinical complications. The aneurysm shrank in size
      at follow-up angiography 6 months after the procedure and will be monitored for
      progressive occlusion. While gross stent malapposition is readily evident after
      stent deployment, minor instances of malapposition may be undetectable by
      standard angiography. Therefore the use of DynaCT imaging may improve
      intraprocedural stent visualization and potentially avert long-term endovascular
      aneurysm treatment complications associated with inadequate stent apposition.

PMID- 24856037
TI  - mTORC2 in the center of cancer metabolic reprogramming.
AB  - Metabolic reprogramming is a central hallmark of cancer, enabling tumor cells to
      obtain the macromolecular precursors and energy needed for rapid tumor growth.
      Understanding how oncogenes coordinate altered signaling with metabolic
      reprogramming and global transcription may yield new insights into tumor
      pathogenesis, and provide a new landscape of promising drug targets, while
      yielding important clues into mechanisms of resistance to the signal transduction
      inhibitors currently in use. We review here the recently identified central
      regulatory role for mechanistic target of rapamycin complex 2 (mTORC2), a
      downstream effector of many cancer-causing mutations, in metabolic reprogramming
      and cancer drug resistance. We consider the impact of mTORC2-related metabolism
      on epigenetics and therapeutics, with a particular focus on the intractable
      malignant brain tumor, glioblastoma multiforme (GBM). 

PMID- 24856040
TI  - Risk of subsequent cutaneous squamous cell carcinoma in patients with melanoma.
AB  - BACKGROUND: Patients with melanoma are at increased risk for cutaneous squamous
      cell carcinomas (SCCs). OBJECTIVE: We sought to examine the incidence of
      subsequent SCC among melanoma survivors and the impact of patient and melanoma
      characteristics on SCC risk. METHODS: Kaiser Permanente Northern California
      members given the diagnosis of melanoma from 2000 to 2005 (n = 6378) were
      followed up through 2009 for a pathology-confirmed SCC. Cox models were used to
      estimate SCC risk. RESULTS: The crude SCC incidence rate was 2.41 per 100 person
      years, and was higher among males and older subjects. In adjusted models
      stratified by age, SCC risk was higher among males (hazard ratio [HR] 1.43, 95%
      confidence interval [CI] 1.22-1.67), those with history of nonmelanoma skin
      cancer (HR 2.56, 95% CI 2.19-2.98), and those with higher tumor sequence numbers
      (HR 1.35, 95% CI 1.01-1.80). SCC risk was lower among non-Hispanic whites (HR
      0.39, 95% CI 0.17-0.86). LIMITATIONS: SCC risk was not examined among members
      without melanoma. CONCLUSIONS: SCCs arise in approximately 12% of patients with
      melanoma over a 5-year period and are more common among males, whites, patients
      older than 60 years, those with prior reportable cancers, and those with history
      of nonmelanoma skin cancer. Clinicians should be vigilant for SCCs among these
      individuals at high risk, and counsel melanoma survivors about their increased
      risk for SCCs.

PMID- 24856042
TI  - Placental alkaline phosphatase de-phosphorylates insulin-like growth factor (IGF)
      binding protein-1.
AB  - BACKGROUND: Insulin-like growth factors (IGF) regulate fetal growth through their
      effects on placenta. Their actions are influenced by IGF binding protein-1.
      Phosphorylated IGFBP-1 (pIGFBP-1) has high affinity for IGF-I and usually
      inhibits IGF-I activity but during pregnancy, it is de-phosphorylated to generate
      lower affinity isoforms and consequently, increased IGF bioavailability. Here we
      investigate the role of placenta in this process. RESULTS: Our data show that
      term human placental explants, but not their conditioned medium, can de
      phosphorylate IGFBP-1 through the action of placental alkaline phosphatase
      (PLAP). DISCUSSION: PLAP-mediated de-phosphorylation of IGFBP-1 may provide a
      mechanism for controlling IGF-I bioavailability and action at the maternal/fetal
      interface.

PMID- 24856041
TI  - Exocyst complex protein expression in the human placenta.
AB  - INTRODUCTION: Protein production and secretion are essential to
      syncytiotrophoblast function and are associated with cytotrophoblast cell fusion
      and differentiation. Syncytiotrophoblast hormone secretion is a crucial
      determinant of maternal-fetal health, and can be misregulated in pathological
      pregnancies. Although, polarized secretion is a key component of placental
      function, the mechanisms underlying this process are poorly understood.
      OBJECTIVE: While the octameric exocyst complex is classically regarded as a
      master regulator of secretion in various mammalian systems, its expression in the
      placenta remained unexplored. We hypothesized that the syncytiotrophoblast would
      express all exocyst complex components and effector proteins requisite for
      vesicle-mediated secretion more abundantly than cytotrophoblasts in tissue
      specimens. METHODS: A two-tiered immunobiological approach was utilized to
      characterize exocyst and ancillary proteins in normal, term human placentas.
      Exocyst protein expression and localization was documented in tissue homogenates
      via immunoblotting and immunofluorescence labeling of placental sections.
      RESULTS: The eight exocyst proteins, EXOC1, 2, 3, 4, 5, 6, 7, and 8, were found
      in the human placenta. In addition, RAB11, an important exocyst complex
      modulator, was also expressed. Exocyst and Rab protein expression appeared to be
      regulated during trophoblast differentiation, as the syncytiotrophoblast
      expressed these proteins with little, if any, expression in cytotrophoblast
      cells. Additionally, exocyst proteins were localized at or near the
      syncytiotrophoblast apical membrane, the major site of placental secretion.
      DISCUSSION/CONCLUSION: Our findings highlight exocyst protein expression as novel
      indicators of trophoblast differentiation. The exocyst's regulated localization
      within the syncytiotrophoblast in conjunction with its well known functions
      suggests a possible role in placental polarized secretion.

PMID- 24856043
TI  - Development of clinical practice guidelines for patients with comorbidity and
      multiple diseases.
AB  - The management of patients with comorbidity and polypathology represents a
      challenge for all healthcare systems. Clinical practice guidelines (CPGs) have
      limitations when applied to this population. The aim of this study is to propose
      the terminology and methodology for optimally approach comorbidity and
      polypathology in the CPGs. Based on a literature review, we suggest a number of
      proposals for the approach in different phases of CPG preparation, with special
      attention to the inclusion of clusters of comorbidity in the initial questions
      the implementation of indirect evidence, the burden of disease management for
      patients and their environment, when establishing recommendations, as well as the
      strategies of dissemination and implementation. These proposals should be
      developed in greater depth with the implication of more agents in order to have
      valid and useful tools for this population. 

PMID- 24856044
TI  - Elephantiasis nostras verrucosa.

PMID- 24856045
TI  - Synthesis of angularly substituted trans-fused hydroindanes by convergent
      coupling of acyclic precursors.
AB  - Angularly substituted trans-fused hydroindanes are now accessible by the direct
      and convergent union of trimethylsilyl (TMS)-alkynes with 4-hydroxy-1,6-enynes by
      a process that forges three C-C bonds, one C-H bond, and two new stereocenters.
      The annulation is proposed to proceed by initial formation of a Ti-alkyne complex
      (with a TMS-alkyne) followed by regioselective alkoxide-directed coupling with
      the enyne, stereoselective intramolecular cycloaddition, elimination of
      phenoxide, 1,3-metallotropic shift, and stereoselective protonation of the
      penultimate allylic organometallic intermediate. Several examples are given to
      demonstrate the compatibility of this reaction with substrates bearing aromatic
      and aliphatic substituents, and an empirical model is presented to accompany the
      stereochemical observations. 

PMID- 24856046
TI  - Microsurgical neurovascular anastomosis: the example of superficial temporal
      artery to middle cerebral artery bypass. Technical principles.
AB  - The superficial temporal artery to the middle cerebral artery (STA-MCA) bypass is
      a good example of cerebrovascular anastomosis. In this article, we describe the
      different stages of the procedure: patient installation, superficial temporal
      artery harvesting, recipient artery exposure, microsurgical anastomosis, and
      closure of the craniotomy. When meticulously performed, with the observance of
      important details at each stage, this technique offers a high rate of technical
      success (patency>90%) with a very low morbi-mortality (respectively 3% and 1%).
      Some anesthetic parameters have to be considered to insure perioperative
      technical and clinical success. STA-MCA bypass is a very useful technique for the
      management of complex or giant aneurysms where surgical treatment sometimes
      requires the sacrifice and revascularization of a main arterial trunk. It is also
      a valuable option for the treatment of chronic and symptomatic hemispheric
      hypoperfusion (Moyamoya disease, carotid or middle cerebral artery occlusion). 

PMID- 24856047
TI  - Brainstem melanomas presenting as a cavernous malformation.
AB  - BACKGROUND: Melanoma lesions in the brainstem can be difficult to distinguish
      radiographically and clinically from cavernous malformations. However, the
      treatment modalities and clinical course of these two diseases differ
      considerably. We report two cases of melanoma presenting as brainstem
      hemorrhages. CASE DESCRIPTION: A 69-year-old male was found to have a hemorrhagic
      lesion of the right dorsal midbrain. After a repeat hemorrhage, the lesion was
      resected and found to be hyperchromatic. Nonetheless, the patient suffered
      rebleeding and died 3 months later. A 62-year-old female was similarly found to
      have an acute pontine hemorrhage. After resection of the lesion, she underwent
      whole-brain radiation therapy but ultimately died 5.5 months later. The
      histopathology of both lesions was consistent with melanoma. CONCLUSIONS:
      Melanoma in the brainstem can mimic cavernous malformations. While management of
      these lesions includes stereotactic radiosurgery, whole-brain radiation, and
      surgical resection, metastatic brainstem melanoma follows an aggressive clinical
      course with a poor prognosis.

PMID- 24856048
TI  - Spontaneous submucosal sphenoidal fistula discovered intraoperatively. A case
      report.
AB  - BACKGROUND AND IMPORTANCE: Skull base spontaneous cerebrospinal fluid fistulas
      have been recently recognized as secondary to pseudotumor cerebri. In most cases,
      they occur in the ethmoid region and the sphenoid bone which is much less
      affected. Regardless of their etiology, the clinical manifestation of skull base
      fistulas is usually the same and includes a rhinorrhea and less frequently an
      otorrhea. We report a case of a cryptic sphenoid cerebrospinal fluid fistula
      discovered intraoperatively during the excision of a pituitary ACTH-secreting
      microadenoma (2mm in diameter). CLINICAL PRESENTATION: A 54-year-old female was
      admitted to our neurosurgery department for Cushing's disease due to a pituitary
      microadenoma. Six months prior to admission, she complained of severe fatigue,
      polyphagia and weight gain. Clinical examination revealed central obesity with a
      body mass index of 45kg/m(2) and other symptoms suggestive of Cushing's disease.
      Hormonal tests and a MR scan revealed a pituitary ACTH-secreting microadenoma.
      During the operative procedure via a transnasal approach, her nasal and sphenoid
      sinus mucosa appeared unusually edematous. After removal of the latter in order
      to approach the sellar floor, a millimetric hole in the bone at the level of the
      optic groove was visualized which let out cerebrospinal fluid under pressure
      without interruption. The microadenoma was macroscopically completely removed
      without any cerebrospinal fluid coming from the pituitary surgical cavity. The
      closing procedure of the sphenoid groove millimetric opening was performed by
      injecting fibrin glue and a lumbar drain was placed indwelling for four days.
      CONCLUSION: This case report describes a cryptic sphenoid submucosal
      cerebrospinal fluid fistula in a patient with Cushing's syndrome. This type of
      case raises the question of the natural evolution of the skull base cerebrospinal
      fluid fistula from its formation to an externalization such as rhinorrhea.

PMID- 24856050
TI  - Unexpected ruptured aneurysm during posterior fossa surgery.
AB  - BACKGROUND AND IMPORTANCE: Surgery is the recommended treatment for unique
      significant cerebellar metastasis, particularly in cases of hydrocephalus.
      Complications of posterior fossa surgery are associated with high risk of
      morbidity and mortality. We present a unique case of unexpected peroperative
      rupture of a cerebellar superior artery aneurysm during posterior fossa surgery.
      CLINICAL PRESENTATION: During posterior cranial fossa surgery, severe arterial
      bleeding occurred in front of the medulla oblongata. Immediate postoperative
      computed tomographic (CT) angiography revealed a fusiform aneurysm from a distal
      branch of the left superior cerebellar artery. CONCLUSION: To our knowledge, this
      is the first reported operative case of unexpected infratentorial ruptured
      aneurysm during posterior fossa surgery.

PMID- 24856049
TI  - Early presentation of primary glioblastoma.
AB  - BACKGROUND: Clinical and neuroimaging findings of glioblastomas (GBM) at an early
      stage have rarely been described and those tumors are most probably under
      diagnosed. Furthermore, their genetic alterations, to our knowledge, have never
      been previously reported. METHODS: We report the clinical as well as neuroimaging
      findings of four early cases of patients with GBM. RESULTS: In our series, early
      stage GBM occurred at a mean age of 57 years. All patients had seizures as their
      first symptom. In all early stages, MRI showed a hyperintense signal on T2
      weighted sequences and an enhancement on GdE-T1WI sequences. A hyperintense
      signal on diffusion sequences with a low ADC value was also found. These early
      observed occurrences of GBM developed rapidly and presented the MRI
      characteristics of classic GBM within a few weeks. The GBM size was multiplied by
      32 in one month. Immunohistochemical analysis indicated the de novo nature of
      these tumors, i.e. absence of mutant IDH1 R132H protein expression, which is a
      diagnostic marker of low-grade diffuse glioma and secondary GBM. CONCLUSIONS: A
      better knowledge of early GBM presentation would allow a more suitable management
      of the patients and may improve their prognosis.

PMID- 24856051
TI  - Structural and mutational analysis of amino acid residues involved in ATP
      specificity of Escherichia coli acetate kinase.
AB  - Acetate kinase (AK) generally utilizes ATP as a phosphoryl donor, but AK from
      Entamoeba histolytica (PPi-ehiAK) uses pyrophosphate (PPi), not ATP, and is PPi
      specific. The determinants of the phosphoryl donor specificity are unknown. Here,
      we inferred 5 candidate amino acid residues associated with this specificity,
      based on structural information. Each candidate residue in Escherichia coli ATP
      specific AK (ATP-ecoAK), which is unable to use PPi, was substituted with the
      respective PPi-ehiAK amino acid residue. Each variant ATP-ecoAK had an increased
      Km for ATP, indicating that the 5 residues are the determinants for the
      specificity to ATP in ATP-ecoAK. Moreover, Asn-337 of ATP-ecoAK was shown to be
      particularly significant for the specificity to ATP. The 5 residues are highly
      conserved in 2625 PPi-ehiAK homologs, implying that almost all organisms have ATP
      dependent, rather than PPi-dependent, AK. 

PMID- 24856052
TI  - Differential regeneration of myocardial infarction depending on the progression
      of disease and the composition of biomimetic hydrogel.
AB  - Hydrogel has been used for regenerating myocardial infraction (MI) as a delivery
      vehicle for cells and growth factors. This study showed that injectable
      hyaluronic acid (HA)-based hydrogels alone would effectively regenerate the
      damaged infarcted heart tissue. We found that there are two major factors of
      regeneration in MI. One is molecular weight of HA and another is the progression
      of MI; sub-acute and chronic. Rat MI model was prepared by ligating the left
      anterior descending coronary artery (LAD). Four weeks after injection of
      hydrogel, functional analysis of the heart and histological analysis was
      assessed. When different molecular weight HA-based hydrogels with 50 kDa, 130
      kDa, and 170 kDa were applied to the infarcted area in the sub-acute model, 50
      kDa HA-based hydrogel showed the most significant regeneration of myocardium as
      well as functional recovery among samples. For the disease progression, 50 kDa HA
      based hydrogels were injected to sub-acute and chronic MI models. The
      regeneration activity was significantly decreased in the chronic models
      reflecting that injection timing of the therapeutic agents is also major
      determinants in the regeneration process. These results suggest that injection
      time and composition of hydrogel are two major points treating MI. 

PMID- 24856053
TI  - Asthma management in children with autism spectrum disorders: pearls for a
      successful clinical encounter.

PMID- 24856054
TI  - Crohn's disease masquerading as an acute abdomen.

PMID- 24856055
TI  - Effects of Glycine max (L.) Merr. soy isoflavone vaginal gel on epithelium
      morphology and estrogen receptor expression in postmenopausal women: a 12-week,
      randomized, double-blind, placebo-controlled trial.
AB  - OBJECTIVE: Evaluate the effects of vaginal administration of isoflavones derived
      from Glycine max (L.) Merr. as a treatment option for vaginal atrophy, on the
      morphology and expression of estrogen receptors in vaginal epithelium of
      postmenopausal women. METHODS: The double-blind, randomized, placebo-controlled,
      clinical trial. Sixty women were treated for 12 weeks with isoflavone vaginal gel
      4% (1g/day) and a placebo gel. After 4 and 12 weeks, the vaginal atrophy symptoms
      were classified at none, mild, moderate and severe and the vaginal cytology were
      taken to determine the maturation value. Vaginal pH was measured at the beginning
      and end of therapy. Microbiopsies in vaginal fornix were performed before the
      treatment and after 12 weeks of treatment. RESULTS: Isoflavone vaginal gel was
      effective for relief of vaginal dryness and dyspareunia symptons and an increase
      in the intermediate and superficial cells was noted. The vaginal pH in the
      isoflavone group was 7.1 at baseline and 5.4 after 12 weeks, whereas in the
      placebo group there was no significant change. A significant increase in
      thickness after treatment was detected in the Isoflavone Group. The percentage of
      estrogen receptor positive cells in vaginal epithelium for the Isoflavone Group
      ranged from 58.5% at the beginning of treatment to 82.6% after 12 weeks. These
      results were superior to placebo gel. CONCLUSION: Glycine max (L.) Merr. at 4%
      vaginal gel on a daily basis in postmenopausal women led to improvements in
      vaginal atrophy symptoms, maturation values, vaginal pH, morphology and
      expression of estrogen receptors in vaginal epithelium. Isoflavones proved good
      treatment options for relief of vulvovaginal atrophy.

PMID- 24856056
TI  - Blood pressure variability predicts cognitive decline in Alzheimer's disease
      patients.
AB  - The aim of our study was to evaluate whether blood pressure variability
      influences the rate of cognitive decline in Alzheimer's disease (AD). Two hundred
      and forty AD patients were periodically evaluated for a 12-month period. The
      blood pressure (BP) status of each patient was defined through mean and
      coefficient of variation for both systolic and diastolic BP. Progression of
      cognitive decline was investigated using the Mini Mental State Examination
      administered at entry and at the end of follow-up. Among the considered BP
      indices, only systolic BP variability explained the decrease in the Mini Mental
      State Examination score after adjustment for confounding variables (multiple
      linear regression: R(2) = 0.603, adjusted R(2) = 0.513; p < 0.001; logistic
      regression model: odds ratio = 2.882, 95% confidence interval = 1.772-4.495; p <
      0.001). The receiver operating characteristic analysis for evaluating the ability
      of systolic BP variability to predict a faster cognitive decline presented an
      area under the curve of 0.913 (95% confidence interval = 0.874-0.953; p < 0.001).
      Our results suggest that BP variability may be added to the list of the potential
      vascular risk factors and included in the evaluation of AD patients to better
      define their risk profile.

PMID- 24856057
TI  - Oxytocin improves emotion recognition for older males.
AB  - Older adults (>=60 years) perform worse than young adults (18-30 years) when
      recognizing facial expressions of emotion. The hypothesized cause of these
      changes might be declines in neurotransmitters that could affect information
      processing within the brain. In the present study, we examined the neuropeptide
      oxytocin that functions to increase neurotransmission. Research suggests that
      oxytocin benefits the emotion recognition of less socially able individuals. Men
      tend to have lower levels of oxytocin and older men tend to have worse emotion
      recognition than older women; therefore, there is reason to think that older men
      will be particularly likely to benefit from oxytocin. We examined this idea using
      a double-blind design, testing 68 older and 68 young adults randomly allocated to
      receive oxytocin nasal spray (20 international units) or placebo. Forty-five
      minutes afterward they completed an emotion recognition task assessing labeling
      accuracy for angry, disgusted, fearful, happy, neutral, and sad faces. Older
      males receiving oxytocin showed improved emotion recognition relative to those
      taking placebo. No differences were found for older females or young adults. We
      hypothesize that oxytocin facilitates emotion recognition by improving
      neurotransmission in the group with the worst emotion recognition.

PMID- 24856059
TI  - trans-Caryophyllene is a natural agonistic ligand for peroxisome proliferator
      activated receptor-alpha.
AB  - Intake of dietary aroma compounds may regulate cellular lipid metabolism. We
      demonstrated that trans-caryophyllene, a flavor compound in plant foods and teas,
      activates peroxisome proliferator-activated receptor (PPAR)-alpha through direct
      interaction with the ligand-binding domain of PPAR-alpha. The agonistic activity
      of trans-caryophyllene was investigated by the luciferase reporter assay, surface
      plasmon resonance, and time-resolved fluorescence resonance energy transfer
      assay. Following the stimulation of cells with trans-caryophyllene, intracellular
      triglyceride concentrations were significantly reduced by 17%, and hepatic fatty
      acid uptake was significantly increased by 31%. The rate of fatty acid oxidation
      was also significantly increased. The expressions of PPAR-alpha and its target
      genes and proteins in fatty acid uptake and oxidation were significantly up
      regulated as well. In HepG2 cells transfected with small interfering RNA of PPAR
      alpha, the effects of trans-caryophyllene on PPAR-alpha responsive gene
      expressions, intracellular triglyceride, fatty acid uptake and oxidation were
      disappeared. These results indicate that the aroma compound, trans-caryophyllene,
      is PPAR-alpha agonist thus regulates cellular lipid metabolism in PPAR-alpha
      dependent manners. 

PMID- 24856058
TI  - Protein-ligand interactions: probing the energetics of a putative cation-pi
      interaction.
AB  - In order to probe the energetics associated with a putative cation-pi
      interaction, thermodynamic parameters are determined for complex formation
      between the Grb2 SH2 domain and tripeptide derivatives of RCO-pTyr-Ac6c-Asn
      wherein the R group is varied to include different alkyl, cycloalkyl, and aryl
      groups. Although an indole ring is reputed to have the strongest interaction with
      a guanidinium ion, binding free energies, DeltaG degrees , for derivatives of RCO
      pTyr-Ac6c-Asn bearing cyclohexyl and phenyl groups were slightly more favorable
      than their indolyl analog. Crystallographic analysis of two complexes reveals
      that test ligands bind in similar poses with the notable exception of the
      relative orientation and proximity of the phenyl and indolyl rings relative to an
      arginine residue of the domain. These spatial orientations are consistent with
      those observed in other cation-pi interactions, but there is no net energetic
      benefit to such an interaction in this biological system. Accordingly, although
      cation-pi interactions are well documented as important noncovalent forces in
      molecular recognition, the energetics of such interactions may be mitigated by
      other nonbonded interactions and solvation effects in protein-ligand
      associations. 

PMID- 24856060
TI  - Peptide chemistry applied to a new family of phenothiazine-containing inhibitors
      of human farnesyltransferase.
AB  - Novel phenothiazine derivatives bearing an amino acid residue were synthesized
      via peptide chemistry, and evaluated for their inhibitory potential on human
      farnesyltransferase. The phenothiazine unit proved to be an important bulky unit
      in the structure of the synthesized inhibitors. Propargyl ester 20 bearing a
      tyrosine residue exhibited the best biological potential in vitro in the present
      study. Further syntheses and biological evaluation of phenothiazine derivatives
      are necessary in order to gain a full view of SAR in this family of
      farnesyltransferase inhibitors. 

PMID- 24856062
TI  - Synthesis and antituberculosis activity of novel 5-styryl-4-(hetero)aryl
      pyrimidines via combination of the Pd-catalyzed Suzuki cross-coupling and S(N)(H)
      reactions.
AB  - Combination of the Suzuki cross-coupling and nucleophilic aromatic substitution
      of hydrogen (SN(H)) reactions proved to be a convenient method for the synthesis
      of 5-styryl-4-(hetero)aryl substituted pyrimidines from commercially available 5
      bromopyrimidine. All intermediate 5-bromo-4-(hetero)aryl substituted pyrimidines
      and also the targeted 5-styryl-4-(hetero)arylpyrimidines were found to be active
      in micromolar concentrations in vitro against Mycobacterium tuberculosis H37Rv,
      avium, terrae, and multi-drug-resistant strain isolated from tuberculosis
      patients in Ural region (Russia). It has been found that some of these compounds
      possess a low toxicity and have a bacteriostatic effect, comparable and even
      higher with that of first-line antituberculosis drugs. 

PMID- 24856061
TI  - Targeting the homologous recombination pathway by small molecule modulators.
AB  - During the last decade, the use of small molecule (MW <500 Da) compounds that
      modulate (inhibit or activate) important proteins of different biological
      pathways became widespread. Recently, the homologous recombination (HR) pathway
      emerged as a target for such modulators. Development of small molecule modulators
      pursues two distinct but not mutually exclusive purposes: to create a research
      tool to study the activities or functions of proteins of interest and to produce
      drugs targeting specific pathologies. Here, we review the progress of small
      molecule development in the area of HR.

PMID- 24856063
TI  - Aryl-substituted aminobenzimidazoles targeting the hepatitis C virus internal
      ribosome entry site.
AB  - We describe the exploration of N1-aryl-substituted benzimidazoles as ligands for
      the hepatitis C virus (HCV) internal ribosome entry site (IRES) RNA. The design
      of the compounds was guided by the co-crystal structure of a benzimidazole viral
      translation inhibitor in complex with the RNA target. Structure-binding activity
      relationships of aryl-substituted benzimidazole ligands were established that
      were consistent with the crystal structure of the translation inhibitor complex. 

PMID- 24856064
TI  - Discovery of N-substituted 7-azaindoline derivatives as potent, orally available
      M1 and M4 muscarinic acetylcholine receptors selective agonists.
AB  - We designed and synthesized novel N-substituted 7-azaindoline derivatives as
      selective M1 and M4 muscarinic acetylcholine receptors (mAChRs) agonists.
      Hybridization of compound 2 with the HTS hit compound 5 followed by optimization
      of the N-substituents of 7-azaindoline led to identification of compound 1, which
      showed highly selective M1 and M4 mAChRs agonistic activity, weak human ether-a
      go-go related gene inhibition, and good bioavailability in multiple animal
      species. 

PMID- 24856065
TI  - Separating the isomers--efficient synthesis of the N-hydroxysuccinimide esters of
      5 and 6-carboxyfluorescein diacetate and 5 and 6-carboxyrhodamine B.
AB  - Diacetate protection of 5 and 6-carboxyfluorescein followed by synthesis of the N
      hydroxysuccinimide esters allowed ready separation of the two isomers on a multi
      gram scale. The 5 and 6-carboxyrhodamine B N-hydroxysuccinimide esters were also
      readily synthesised and separated. 

PMID- 24856066
TI  - Fullerene derivatives as a new class of inhibitors of protein tyrosine
      phosphatases.
AB  - In this study, we identified water-soluble C60 and C70 fullerene derivatives as a
      novel class of protein tyrosine phosphatase inhibitors. The evaluated compounds
      were found to inhibit CD45, PTP1B, TC-PTP, SHP2, and PTPbeta with IC50 values in
      the low micromolar to high nanomolar range. These results demonstrate a new
      strategy for designing effective nanoscale protein tyrosine phosphatase
      inhibitors. 

PMID- 24856067
TI  - Studies on molecular properties prediction, antitubercular and antimicrobial
      activities of novel quinoline based pyrimidine motifs.
AB  - In the present study, a series of 3-((6-(2,6-dichloroquinolin-3-yl)-4-aryl-1,6
      dihydro-pyrimidin-2-yl)thio)propanenitriles 5a-o were synthesized and subjected
      to molecular properties prediction and drug-likeness model score by
      Molinspiration property calculation toolkit and MolSoft software, respectively.
      Compound 5m (4-OCH3) was found to be maximum drug-likeness model score (0.42).
      Among the screened compounds, 5m showed the most promising antitubercular
      activity with MIC of 0.20 MUg/mL, while compounds 5g, 5k and 5m displayed broad
      spectrum antibacterial activity against all the bacterial strains. Moreover,
      compound 5k was found to be the most potent antifungal agent. Further, the
      results of preliminary MTT cytotoxicity studies on HeLa cells suggested that
      potent antimicrobial activity of 5g, 5k and 5m was escorted by low cytotoxicity.

PMID- 24856068
TI  - Pharmacophore based virtual screening, molecular docking and biological
      evaluation to identify novel PDE5 inhibitors with vasodilatory activity.
AB  - Prompted by the role of PDE5 and its closely associated cAMP and cGMP in
      hypertension, we have attempted to discover novel PDE5 inhibitors through ligand
      based virtual screening. Rigorously validated model comprising of one HBA, one HY
      and one RA was used as a query to search the NCI database leading to retrieval of
      many compounds which were screened on the basis of estimated activity, fit value
      and Lipinski's violation. Selected compounds were subjected to docking studies
      which resulted into visualization of potential interaction capabilities of NCI
      compounds in line to pharmacophoric features. Finally three compounds were
      subjected to in vitro evaluation using the isolated rat aortic model. The results
      showed that all three compounds are potent and novel PDE5 inhibitors with
      vasodilatory activity range from 10(-2) to 10(-5) M.

PMID- 24856069
TI  - Editorial: surface electrocardiogram remains alive in the XXI century.

PMID- 24856070
TI  - Editorial comment.

PMID- 24856074
TI  - Characterization of the interaction between AFM tips and surface nanobubbles.
AB  - While the presence of gaseous enclosures observed at various solid-water
      interfaces, the so-called "surface nanobubles", has been confirmed by many groups
      in recent years, their formation, properties, and stability have not been
      convincingly and exhaustively explained. Here we report on an atomic force
      microscopy (AFM) study of argon nanobubbles on highly oriented pyrolitic graphite
      (HOPG) in water to elucidate the properties of nanobubble surfaces and the
      mechanism of AFM tip-nanobubble interaction. In particular, the deformation of
      the nanobubble-water interface by the AFM tip and the question whether the AFM
      tip penetrates the nanobubble during scanning were addressed by this combined
      intermittent contact (tapping) mode and force volume AFM study. We found that the
      stiffness of nanobubbles was smaller than the cantilever spring constant and
      comparable with the surface tension of water. The interaction with the AFM tip
      resulted in severe quasi-linear deformation of the bubbles; however, in the case
      of tip-bubble attraction, the interface deformed toward the tip. We tested two
      models of tip-bubble interaction, namely, the capillary force and the dynamic
      interaction model, and found, depending on the tip properties, good agreement
      with experimental data. The results showed that the tip-bubble interaction
      strength and the magnitude of the bubble deformation depend strongly on tip and
      bubble geometry and on tip and substrate material, and are very sensitive to the
      presence of contaminations that alter the interfacial tension. In particular,
      nanobubbles interacted differently with hydrophilic and hydrophobic AFM tips,
      which resulted in qualitatively and quantitatively different force curves
      measured on the bubbles in the experiments. To minimize bubble deformation and
      obtain reliable AFM results, nanobubbles must be measured with a sharp
      hydrophilic tip and with a cantilever having a very low spring constant in a
      contamination-free system. 

PMID- 24856072
TI  - A survey on Swiss women's preferred menstrual/withdrawal bleeding pattern over
      different phases of reproductive life and with use of hormonal contraception.
AB  - BACKGROUND: Today, options for bleeding-free lifestyle are actively promoted by
      the media, the pharmaceutical industry and health specialists. With regard to
      contraceptive counselling it is important to find out what women really want.
      METHODS: In the present study we collected information on women's attitudes
      towards monthly bleeding and preferences, if they could have the option to modify
      their individual bleeding pattern. Furthermore we evaluated the preferences with
      use of combined hormonal contraceptives (CHCs). Switzerland has never been
      surveyed before with regard to these issues. Questionnaires were distributed in
      our family planning clinic and two outdoor offices to clients aged 15 to 19
      years, 25 to 34 years, and 45 to 49 years. RESULTS: Of 530 questionnaires, 292
      were eligible for analysis. Around 50 of the participants would appreciate having
      fewer menstrual period-related symptoms. Some 37% preferred experiencing a
      monthly bleeding; 32% opted for every 2 to 6 months; and 29%, for no bleeding at
      all. This heterogeneous distribution did not differ between clients with and
      without menstrual symptoms. With regard to CHC use, predictable bleeding was
      rated as very positive and breakthrough bleeding as negative. CONCLUSION:
      Contraceptive counsellors should be aware that women's wishes differ widely.
      Predictability of bleeding seems to be more important to them than postponing it.

PMID- 24856076
TI  - Phosphaannulation by palladium-catalyzed carbonylation of C-H bonds of phosphonic
      and phosphinic acids.
AB  - An efficient phosphaannulation by Pd-catalyzed carbonylation of C-H bonds of
      phosphonic and phosphinic acids for the synthesis of oxaphosphorinanone oxides is
      reported. These compounds are novel phosphorus heterocyclic scaffolds, thus
      opening a new avenue to sequential C-C/C-O bond formation in one pot. 

PMID- 24856077
TI  - Autofluorescence thoracoscopy in pleural disease: does it have clinical
      relevance?
AB  - Thoracoscopy has proved to be a reliable tool to demonstrate or exclude pleural
      malignancy, with a diagnostic yield of at least 90%. (Auto)fluorescence
      thoracoscopy is a technique used in clinical practice for the early detection of
      malignant changes in the pleura in order to increase the detection rate of early
      malignant disease. The sensitivity of autofluorescence thoracoscopy for detecting
      malignant lesions on the pleural surface was, in our experience, 100% and the
      specificity was 75%. Autofluorescence thoracoscopy is still in the preclinical
      research stage and not yet ready for routine use in clinical practice. It will
      neither increase the (already very high) diagnostic yield of thoracoscopy nor
      change treatment in patients suffering from malignant pleural disease. 

PMID- 24856078
TI  - Ceftolozane/tazobactam activity tested against Gram-negative bacterial isolates
      from hospitalised patients with pneumonia in US and European medical centres
      (2012).
AB  - During 2012, a total of 2968 isolates were consecutively collected from 59
      medical centres in the USA and 15 European countries from hospitalised patients
      with pneumonia. Ceftolozane/tazobactam (tazobactam at a fixed concentration of
      4mg/L) and comparator agents were tested by reference methods, and MIC endpoints
      were interpreted by CLSI (2013) and EUCAST (2013) breakpoint criteria.
      Pseudomonas aeruginosa was the most common isolated pathogen (1019 strains;
      34.3%), and ceftolozane/tazobactam was the most active beta-lactam tested against
      P. aeruginosa (MIC50/90, 0.5/4 mg/L; 94.1% inhibited at <= 8 mg/L). P. aeruginosa
      exhibited moderate susceptibility to meropenem (MIC50/90, 0.5/>8 mg/L; 73.7%
      susceptible), ceftazidime (MIC50/90, 2/>32 mg/L; 73.6% susceptible), cefepime
      (MIC50/90, 4/>16 mg/L; 76.5% susceptible), piperacillin/tazobactam (MIC50/90,
      8/>64 mg/L; 69.5% susceptible), levofloxacin [MIC50/90, 0.5/>4 mg/L; 69.9/61.0%
      susceptible (CLSI/EUCAST criteria)] and gentamicin (MIC50/90, 2/>8 mg/L; 80.7%
      susceptible). Ceftolozane/tazobactam exhibited activity against many ceftazidime
      non-susceptible, meropenem-non-susceptible and piperacillin/tazobactam-non
      susceptible, multidrug-resistant (MDR) and extensively drug-resistant (XDR) P.
      aeruginosa isolates. Ceftolozane/tazobactam was active (MIC50/90, 0.25/4mg/L;
      94.6% inhibited at <= 8 mg/L) against 1530 Enterobacteriaceae, including activity
      against many MDR and XDR strains. MDR and XDR prevalence varied widely between
      countries both for P. aeruginosa (24.1% MDR and 17.1% XDR overall) and
      Enterobacteriaceae (15.4% MDR and 2.7% XDR overall). All beta-lactams had limited
      activity against Acinetobacter spp. and Stenotrophomonas maltophilia.
      Ceftolozane/tazobactam demonstrated greater in vitro activity than currently
      available cephalosporins, carbapenems and piperacillin/tazobactam when tested
      against P. aeruginosa. In addition, ceftolozane/tazobactam demonstrated greater
      activity than contemporary cephalosporins and piperacillin/tazobactam when tested
      against most Enterobacteriaceae.

PMID- 24856084
TI  - The effect of pre-donation hypotension on whole blood donor adverse reactions: a
      systematic review.
AB  - Blood services are reliant upon healthy blood donors to provide a safe and
      adequate supply of blood products. Inappropriate variables contained within blood
      donor exclusion criteria can defer potentially appropriate donors. The aim of
      this systematic review was to examine the effect of low pre-donation blood
      pressure, as compared with normal blood pressure, on adverse events in allogeneic
      whole blood donors. A systematic review was performed using highly sensitive
      search strategies within five databases (Cochrane Central Register of Controlled
      Trials, CINAHL, Embase, MEDLINE, and Web of Science) from inception date until
      April 12, 2013. Out of 8305 records, 10 observational studies were identified
      that addressed the question. Five of these studies (with a combined total of
      1,482,020 donations and 2903 donors) included either a statistical analysis or an
      appropriate study design that controlled for possible confounding factors. Based
      on the currently available evidence, hypotension has not been shown to be an
      independent predictive factor for donor complications. However, the overall
      quality of evidence was rather limited and rated 'low,' using the GRADE approach.
      In conclusion there is currently no evidence that hypotensive blood donors have a
      greater risk for donor adverse events compared with their normotensive
      counterparts.

PMID- 24856085
TI  - Modeling materials and processes in hybrid/organic photovoltaics: from dye
      sensitized to perovskite solar cells.
AB  - CONSPECTUS: Over the last 2 decades, researchers have invested enormous research
      effort into hybrid/organic photovoltaics, leading to the recent launch of the
      first commercial products that use this technology. Dye-sensitized solar cells
      (DSCs) have shown clear advantages over competing technologies. The top certified
      efficiency of DSCs exceeds 11%, and the laboratory-cell efficiency is greater
      than 13%. In 2012, the first reports of high efficiency solid-state DSCs based on
      organohalide lead perovskites completely revolutionized the field. These
      materials are used as light absorbers in DSCs and as light-harvesting materials
      and electron conductors in meso-superstructured and flat heterojunction solar
      cells and show certified efficiencies that exceed 17%. To effectively compete
      with conventional photovoltaics, emerging technologies such as DSCs need to
      achieve higher efficiency and stability, while maintaining low production costs.
      Many of the advances in the DSC field have relied on the computational design and
      screening of new materials, with researchers examining material characteristics
      that can improve device performance or stability. Suitable modeling strategies
      allow researchers to observe the otherwise inaccessible but crucial
      heterointerfaces that control the operation of DSCs, offering the opportunity to
      develop new and more efficient materials and optimize processes. In this Account,
      we present a unified view of recent computational modeling research examining
      DSCs, illustrating how the principles and simulation tools used for these systems
      can also be adapted to study the emerging field of perovskite solar cells.
      Researchers have widely applied first-principles modeling to the DSC field and,
      more recently, to perovskite-based solar cells. DFT/TDDFT methods provide the
      basic framework to describe most of the desired materials and interfacial
      properties, and Car-Parrinello molecular dynamics allow researchers the further
      ability to sample local minima and dynamical fluctuations at finite temperatures.
      However, conventional DFT/TDDFT has some limitations, which can be overcome in
      part by tailored solutions or using many body perturbation theory within the GW
      approach, which is however more computationally intensive. Relativistic effects,
      such as spin-orbit coupling, are also included in simulations since they are
      fundamental for addressing systems that contain heavy atoms. We illustrate the
      performance of the proposed simulation toolbox along with the fundamental
      modeling strategies using selected examples of relevant isolated device
      constituents, including dye and perovskite absorbers, metal-oxide surfaces and
      nanoparticles, and hole transporters. We critically assess the accuracy of
      various computational approaches against the related experimental data. We
      analyze the representative interfaces that control the operational mechanism of
      the devices, including dye-sensitized TiO2/hole transporter and organohalide lead
      perovskite/TiO2, and the results reveal fundamental aspects of the device's
      operational mechanism. Although the modeling of DSCs is relatively mature, the
      recent "perovskite storm" has presented new problems and new modeling challenges,
      such as understanding exciton formation and dissociation at interfaces and
      carrier recombination in these materials.

PMID- 24856087
TI  - Effect of topology of poly(L-lactide-co-epsilon-caprolactone) scaffolds on the
      response of cultured human umbilical cord Wharton's jelly-derived mesenchymal
      stem cells and neuroblastoma cell lines.
AB  - In this study, for the first time, a biodegradable poly(L-lactide-co-epsilon
      caprolactone), PLC 67:33 copolymer was developed for use as temporary scaffolds
      in reconstructive nerve surgery. The effect of the surface topology and pore
      architecture were studied on the biocompatibility for supporting the growth of
      human umbilical cord Wharton's jelly-derived mesenchymal stem cells (hWJ-MSCs)
      and human neuroblastoma cells (hNBCs) as cell models. Porous PLC membranes were
      prepared by electrospinning and phase immersion precipitation with particulate
      leaching and nonporous PLC membranes were prepared by solvent casting. From the
      results, the porous PLC membranes can support hWJ-MSCs and hNBCs cells better
      than the nonporous PLC membrane, and the interconnected pore scaffold prepared by
      electrospinning exhibited a more significant supporting attachment of the cells
      than the open pore and nonporous membranes. We can consider that these
      electrospun PLC membranes with 3-D interconnecting fiber networks and a high
      porosity warrant a potential use as nerve guides in reconstructive nerve surgery.

PMID- 24856086
TI  - Enrichment of chemical libraries docked to protein conformational ensembles and
      application to aldehyde dehydrogenase 2.
AB  - Molecular recognition is a complex process that involves a large ensemble of
      structures of the receptor and ligand. Yet, most structure-based virtual
      screening is carried out on a single structure typically from X-ray
      crystallography. Explicit-solvent molecular dynamics (MD) simulations offer an
      opportunity to sample multiple conformational states of a protein. Here we
      evaluate our recently developed scoring method SVMSP in its ability to enrich
      chemical libraries docked to MD structures of seven proteins from the Directory
      of Useful Decoys (DUD). SVMSP is a target-specific rescoring method that combines
      machine learning with statistical potentials. We find that enrichment power as
      measured by the area under the ROC curve (ROC-AUC) is not affected by increasing
      the number of MD structures. Among individual MD snapshots, many exhibited
      enrichment that was significantly better than the crystal structure, but no
      correlation between enrichment and structural deviation from crystal structure
      was found. We followed an innovative approach by training SVMSP scoring models
      using MD structures (SVMSPMD). The resulting models were applied to two difficult
      cases (p38 and CDK2) for which enrichment was not better than random. We found
      remarkable increase in enrichment power, particularly for p38, where the ROC-AUC
      increased by 0.30 to 0.85. Finally, we explored approaches for a priori
      identification of MD snapshots with high enrichment power from an MD simulation
      in the absence of active compounds. We found that the use of randomly selected
      compounds docked to the target of interest using SVMSP led to notable enrichment
      for EGFR and Src MD snapshots. SVMSP rescoring of protein-compound MD structures
      was applied for the search of small-molecule inhibitors of the mitochondrial
      enzyme aldehyde dehydrogenase 2 (ALDH2). Rank-ordering of a commercial library of
      50 000 compounds docked to MD structures of ALDH2 led to five small-molecule
      inhibitors. Four compounds had IC50s below 5 MUM. These compounds serve as leads
      for the design and synthesis of more potent and selective ALDH2 inhibitors. 

PMID- 24856088
TI  - Identification of possible virulence marker from Campylobacter jejuni isolates.
AB  - A novel protein translocation system, the type-6 secretion system (T6SS), may
      play a role in virulence of Campylobacter jejuni. We investigated 181 C. jejuni
      isolates from humans, chickens, and environmental sources in Vietnam, Thailand,
      Pakistan, and the United Kingdom for T6SS. The marker was most prevalent in human
      and chicken isolates from Vietnam. 

PMID- 24856089
TI  - Magnetic resonance evaluation of TruFit(r) plugs for the treatment of
      osteochondral lesions of the knee shows the poor characteristics of the repair
      tissue.
AB  - BACKGROUND: Treatment of osteochondral lesions of the knee with synthetic
      scaffolds seems to offer a good surgical option preventing donor site morbidity.
      The TruFit(r) plug has frequently been shown to not properly incorporate into.
      OBJECTIVE: To evaluate the relationship between MRI findings and functional
      scores of patients with osteochondral lesions of the knee treated with TruFit(r).
      METHODS: Patients were evaluated with MOCART score for magnetic resonance imaging
      assessment of the repair tissue. KOOS, SF-36 and VAS were used for clinical
      evaluation. Correlation between size of the treated chondral defect and
      functional scores was also analyzed. RESULTS: Fifty-seven patients with median
      follow-up of 44.8 months (range 24-73) were included. KOOS, SF-36 and VAS
      improved from a mean 58.5, 53.9 and 8.5 points to a mean 87.4, 86.6 and 1.2 at
      last follow-up (p<0.001). Larger lesions showed less improvement in KOOS (p=0.04)
      and SF-36 (p=0.029). Median Tegner values were restored to preinjury situation
      (5, range 2-10). Mean MOCART score was 43.2 +/- 16.1. Although the cartilage
      layer had good integration, it showed high heterogeneity and no filling of the
      subchondral bone layer. CONCLUSIONS: TruFit(r) failed to restore the normal MRI
      aspect of the subchondral bone and lamina in most cases. The appearance of the
      chondral layer in MRI was partially re-established. This unfavourable MRI
      appearance did not adversely influence the patient's outcome in the short time
      and they restored their previous level of activity. There was an inverse linear
      relationship between the size of the lesion and the functional scores. LEVEL OF
      EVIDENCE: Therapeutic case series; level 4.

PMID- 24856090
TI  - Influence of the posterior tibial slope on the flexion gap in total knee
      arthroplasty.
AB  - BACKGROUND: Adjusting the joint gap length to be equal in both extension and
      flexion is an important issue in total knee arthroplasty (TKA). It is generally
      acknowledged that posterior tibial slope affects the flexion gap; however, the
      extent to which changes in the tibial slope angle directly affect the flexion gap
      remains unclear. This study aimed to clarify the influence of tibial slope
      changes on the flexion gap in cruciate-retaining (CR) or posterior-stabilizing
      (PS) TKA. METHODS: The flexion gap was measured using a tensor device with the
      femoral trial component in 20 cases each of CR- and PS-TKA. A wedge plate with a
      5 degrees  inclination was placed on the tibial cut surface by switching its
      front-back direction to increase or decrease the tibial slope by 5 degrees . The
      flexion gap after changing the tibial slope was compared to that of the neutral
      slope measured with a flat plate that had the same thickness as that of the wedge
      plate center. RESULTS: When the tibial slope decreased or increased by 5 degrees
      , the flexion gap decreased or increased by 1.9 +/- 0.6mm or 1.8 +/- 0.4mm,
      respectively, with CR-TKA and 1.2 +/- 0.4mm or 1.1 +/- 0.3mm, respectively, with
      PS-TKA. CONCLUSIONS: The influence of changing the tibial slope by 5 degrees  on
      the flexion gap was approximately 2mm with CR-TKA and 1mm with PS-TKA. CLINICAL
      RELEVANCE: This information is useful when considering the effect of manipulating
      the tibial slope on the flexion gap when performing CR- or PS-TKA.

PMID- 24856091
TI  - Famines, food insecurity and coral reef 'Ponzi' fisheries.

PMID- 24856096
TI  - Postnatal care - current issues and future challenges.

PMID- 24856092
TI  - Oil sorbents with high sorption capacity, oil/water selectivity and reusability
      for oil spill cleanup.
AB  - A sorbent for oil spill cleanup was prepared through a novel strategy by treating
      polyurethane sponges with silica sol and gasoline successively. The oil sorption
      capacity, oil/water selectivity, reusability and sorption mechanism of prepared
      sorbent were studied. The results showed that the prepared sorbent exhibited high
      sorption capacity and excellent oil/water selectivity. 1g of the prepared sorbent
      could adsorb more than 100 g of motor oil, while it only picks up less than 0.1 g
      of water from an oil-water interface under both static and dynamic conditions.
      More than 70% of the sorption capacity remained after 15 successive sorption
      squeezing cycles, which suggests an extraordinary high reusability. The prepared
      sorbent is a better alternative of the commercial polypropylene sorbent which are
      being used nowadays.

PMID- 24856097
TI  - A high-fructose diet induces hippocampal insulin resistance and exacerbates
      memory deficits in male Sprague-Dawley rats.
AB  - The purpose of this study was to investigate the effects of a long-term high
      fructose diet on the insulin-signaling pathway of the hippocampus. Sprague-Dawley
      rats were fed either on a control (0% fructose solution) or high-fructose diet
      (10% fructose solution). Food intake and body mass were measured regularly. Eight
      months later, peripheral insulin sensitivity, the activity of the hippocampal
      insulin pathway, and memory tasks were assessed. Compared to the control group,
      the high fructose group exhibited more weight gain, peripheral insulin
      resistance, metabolic disorders, and memory impairments. In addition, insulin
      signaling in the hippocampus was attenuated in the high fructose group. These
      results suggested that a high-fructose diet induced peripheral insulin resistance
      and an abnormal insulin-signaling pathway in the hippocampus which exacerbated
      memory deficits in the rats. 

PMID- 24856099
TI  - Palladium-catalyzed alpha-arylation of aryloxyketones for the synthesis of 2,3
      disubstituted benzofurans.
AB  - A highly efficient palladium-catalyzed alpha-arylation of aryloxyketones has been
      developed, allowing for facile installation of various (hetero)aryl groups at C2
      position in good to excellent yields. Subsequent cyclodehydration of the
      resulting alpha-arylated aryloxyketones provided rapid access to diverse 2,3
      disubstitured benzofurans. 

PMID- 24856098
TI  - Novel reassortant influenza A(H5N8) viruses, South Korea, 2014.

PMID- 24856100
TI  - Cultured meat: every village its own factory?
AB  - Rising global demand for meat will result in increased environmental pollution,
      energy consumption, and animal suffering. Cultured meat, produced in an animal
      cell cultivation process, is a technically feasible alternative lacking these
      disadvantages, provided that an animal-component-free growth medium can be
      developed. Small-scale production looks particularly promising, not only
      technologically but also for societal acceptance. Economic feasibility, however,
      emerges as the real obstacle. 

PMID- 24856101
TI  - Real-time ultrasound transducer localization in fluoroscopy images by transfer
      learning from synthetic training data.
AB  - The fusion of image data from trans-esophageal echography (TEE) and X-ray
      fluoroscopy is attracting increasing interest in minimally-invasive treatment of
      structural heart disease. In order to calculate the needed transformation between
      both imaging systems, we employ a discriminative learning (DL) based approach to
      localize the TEE transducer in X-ray images. The successful application of DL
      methods is strongly dependent on the available training data, which entails three
      challenges: (1) the transducer can move with six degrees of freedom meaning it
      requires a large number of images to represent its appearance, (2) manual
      labeling is time consuming, and (3) manual labeling has inherent errors. This
      paper proposes to generate the required training data automatically from a single
      volumetric image of the transducer. In order to adapt this system to real X-ray
      data, we use unlabeled fluoroscopy images to estimate differences in feature
      space density and correct covariate shift by instance weighting. Two approaches
      for instance weighting, probabilistic classification and Kullback-Leibler
      importance estimation (KLIEP), are evaluated for different stages of the proposed
      DL pipeline. An analysis on more than 1900 images reveals that our approach
      reduces detection failures from 7.3% in cross validation on the test set to zero
      and improves the localization error from 1.5 to 0.8mm. Due to the automatic
      generation of training data, the proposed system is highly flexible and can be
      adapted to any medical device with minimal efforts. 

PMID- 24856102
TI  - Endogenous protein "barcode" for data validation and normalization in
      quantitative MS analysis.
AB  - Quantitative proteomic experiments with mass spectrometry detection are typically
      conducted by using stable isotope labeling and label-free quantitation
      approaches. Proteins with housekeeping functions and stable expression level such
      actin, tubulin, and glyceraldehyde-3-phosphate dehydrogenase are frequently used
      as endogenous controls. Recent studies have shown that the expression level of
      such common housekeeping proteins is, in fact, dependent on various factors such
      as cell type, cell cycle, or disease status and can change in response to a
      biochemical stimulation. The interference of such phenomena can, therefore,
      substantially compromise their use for data validation, alter the interpretation
      of results, and lead to erroneous conclusions. In this work, we advance the
      concept of a protein "barcode" for data normalization and validation in
      quantitative proteomic experiments. The barcode comprises a novel set of proteins
      that was generated from cell cycle experiments performed with MCF7, an estrogen
      receptor positive breast cancer cell line, and MCF10A, a nontumorigenic
      immortalized breast cell line. The protein set was selected from a list of ~3700
      proteins identified in different cellular subfractions and cell cycle stages of
      MCF7/MCF10A cells, based on the stability of spectral count data generated with
      an LTQ ion trap mass spectrometer. A total of 11 proteins qualified as endogenous
      standards for the nuclear and 62 for the cytoplasmic barcode, respectively. The
      validation of the protein sets was performed with a complementary SKBR3/Her2+
      cell line.

PMID- 24856103
TI  - A PEG-Fmoc conjugate as a nanocarrier for paclitaxel.
AB  - We report here that a simple, well-defined, and easy-to-scale up nanocarrier,
      PEG5000-lysyl-(alpha-Fmoc-epsilon-t-Boc-lysine)2 conjugate (PEG-Fmoc), provides
      high loading capacity, excellent formulation stability and low systemic toxicity
      for paclitaxel (PTX), a first-line chemotherapeutic agent for various types of
      cancers. 9-Fluorenylmethoxycarbonyl (Fmoc) was incorporated into the nanocarrier
      as a functional building block to interact with drug molecules. PEG-Fmoc was
      synthesized via a three-step synthetic route, and it readily interacted with PTX
      to form mixed nanomicelles of small particle size (25-30 nm). The PTX loading
      capacity was about 36%, which stands well among the reported micellar systems.
      PTX entrapment in this micellar system is achieved largely via an Fmoc/PTX pi-pi
      stacking interaction, which was demonstrated by fluorescence quenching studies
      and (13)C NMR. PTX formulated in PEG-Fmoc micelles demonstrated sustained release
      kinetics, and in vivo distribution study via near infrared fluorescence imaging
      demonstrated an effective delivery of Cy5.5-labled PTX to tumor sites. The
      maximal tolerated dose for PTX/PEG-Fmoc (MTD > 120 mg PTX/kg) is higher than
      those for most reported PTX formulations, and in vivo therapeutic study exhibited
      a significantly improved antitumor activity than Taxol, a clinically used
      formulation of PTX. Our system may hold promise as a simple, safe, and effective
      delivery system for PTX with a potential for rapid translation into clinical
      study.

PMID- 24856104
TI  - Macrophage polarization in response to ECM coated polypropylene mesh.
AB  - The host response to implanted biomaterials is a highly regulated process that
      influences device functionality and clinical outcome. Non-degradable
      biomaterials, such as knitted polypropylene mesh, frequently elicit a chronic
      foreign body reaction with resultant fibrosis. Previous studies have shown that
      an extracellular matrix (ECM) hydrogel coating of polypropylene mesh reduces the
      intensity of the foreign body reaction, though the mode of action is unknown.
      Macrophage participation plays a key role in the development of the foreign body
      reaction to biomaterials, and therefore the present study investigated macrophage
      polarization following mesh implantation. Spatiotemporal analysis of macrophage
      polarization was conducted in response to uncoated polypropylene mesh and mesh
      coated with hydrated and dry forms of ECM hydrogels derived from either dermis or
      urinary bladder. Pro-inflammatory M1 macrophages (CD86+/CD68+), alternatively
      activated M2 macrophages (CD206+/CD68+), and foreign body giant cells were
      quantified between 3 and 35 days. Uncoated polypropylene mesh elicited a dominant
      M1 response at the mesh fiber surface, which was decreased by each ECM coating
      type beginning at 7 days. The diminished M1 response was accompanied by a
      reduction in the number of foreign body giant cells at 14 and 35 days, though
      there was a minimal effect upon the number of M2 macrophages at any time. These
      results show that ECM coatings attenuate the M1 macrophage response and increase
      the M2/M1 ratio to polypropylene mesh in vivo.

PMID- 24856106
TI  - Surface plasma modification and tropoelastin coating of a polyurethane co-polymer
      for enhanced cell attachment and reduced thrombogenicity.
AB  - Polymers currently utilized for dermal and vascular applications possess sub
      optimal biocompatibility which reduces their efficacy. Improving the cell-binding
      and blood-contacting properties of these polymers would substantially improve
      their clinical utility. Tropoelastin is a highly extensible extracellular matrix
      protein with beneficial cell interactive and low thrombogenic properties. We
      transferred these benefits to the polyurethane block copolymer Elast-Eon E2A
      through a specific combination of surface plasma modifications and coating with
      human tropoelastin. The cell-binding activity of bound tropoelastin was modulated
      by ion implantation of the underlying polymer, and correlated with surface
      hydrophobicity, carbon and oxygen content. This combined treatment enhanced human
      dermal fibroblast (HDF) and human umbilical vein endothelial cell (HUVEC)
      attachment, cytoskeletal assembly and viability, combined with elevated PECAM-1
      staining of HUVEC cell junctions. The thrombogenicity of the polymer was
      ameliorated by tropoelastin coating. We propose that a combination of metered
      plasma treatment and tropoelastin coating of Elast-Eon can serve to improve the
      biological performance of implantable devices such as vascular conduits. 

PMID- 24856105
TI  - A comparison of bone regeneration with human mesenchymal stem cells and muscle
      derived stem cells and the critical role of BMP.
AB  - Adult multipotent stem cells have been isolated from a variety of human tissues
      including human skeletal muscle, which represent an easily accessible source of
      stem cells. It has been shown that human skeletal muscle-derived stem cells
      (hMDSCs) are muscle-derived mesenchymal stem cells capable of multipotent
      differentiation. Although hMDSCs can undergo osteogenic differentiation and form
      bone when genetically modified to express BMP2; it is still unclear whether
      hMDSCs are as efficient as human bone marrow mesenchymal stem cells (hBMMSCs) for
      bone regeneration. The current study aimed to address this question by performing
      a parallel comparison between hMDSCs and hBMMSCs to evaluate their osteogenic and
      bone regeneration capacities. Our results demonstrated that hMDSCs and hBMMSCs
      had similar osteogenic-related gene expression profiles and had similar
      osteogenic differentiation capacities in vitro when transduced to express BMP2.
      Both the untransduced hMDSCs and hBMMSCs formed very negligible amounts of bone
      in the critical sized bone defect model when using a fibrin sealant scaffold;
      however, when genetically modified with lenti-BMP2, both populations successfully
      regenerated bone in the defect area. No significant differences were found in the
      newly formed bone volumes and bone defect coverage between the hMDSC and hBMMSC
      groups. Although both cell types formed mature bone tissue by 6 weeks post
      implantation, the newly formed bone in the hMDSCs group underwent quicker
      remodelling than the hBMMSCs group. In conclusion, our results demonstrated that
      hMDSCs are as efficient as hBMMSCs in terms of their bone regeneration capacity;
      however, both cell types required genetic modification with BMP in order to
      regenerate bone in vivo.

PMID- 24856108
TI  - Anti-oxidative effects and harmlessness of asymmetric Au@Fe3O4 Janus particles on
      human blood cells.
AB  - The physical properties of asymmetric Janus particles are highly promising for
      future biomedical applications. However, only a few data is available on their
      biological impact on human cells. We investigated the biological impact of
      different Au@Fe3O4 Janus particle formulations in vitro to analyse specific
      uptake modalities and their potential cytotoxic effects on human cells of the
      blood regarding intravenous injection. We demonstrate that Au@Fe3O4 Janus
      particles exhibit a similar or even better biocompatibility compared to the well
      studied spherical iron oxide nanoparticles. The impact of Janus particles on
      cells depends mainly on three factors. (1) Surface functionalization: NH2
      functionalization of the Au or iron oxide domain induces a pronounced reduction
      of cell viability in contrast to non-functionalized variants which is caused by
      the damage of intracellular membranes. (2) The nature of the metal oxide
      component, greatly affects cell viability, as shown by a comparison with Au@MnO
      Janus particles. (3) The overall surface charge and the size of nanoparticles
      have a higher impact on internalization and cellular metabolism than the Janus
      character per se. Interestingly, Janus particle associated DNA damage is
      independent of the effects on the cellular ATP level. However, not only the
      structure and functionalization of the Janus particle surface determines the
      particle's adhesion and intracellular fate, but also the constitution of the cell
      surface as shown by different modification experiments. The multifactorial in
      vitro approach presented in this study demonstrated the high capability of the
      Janus particles. Especially Au@Fe3O4 Janus particles bear great potential for
      applications in vivo.

PMID- 24856107
TI  - Molecular modeling of polynucleotide complexes.
AB  - Delivery of polynucleotides into patient cells is a promising strategy for
      treatment of genetic disorders. Gene therapy aims to either synthesize desired
      proteins (DNA delivery) or suppress expression of endogenous genes (siRNA
      delivery). Carriers constitute an important part of gene therapeutics due to
      limitations arising from the pharmacokinetics of polynucleotides. Non-viral
      carriers such as polymers and lipids protect polynucleotides from intra and
      extracellular threats and facilitate formation of cell-permeable nanoparticles
      through shielding and/or bridging multiple polynucleotide molecules. Formation of
      nanoparticulate systems with optimal features, their cellular uptake and
      intracellular trafficking are crucial steps for an effective gene therapy.
      Despite the great amount of experimental work pursued, critical features of the
      nanoparticles as well as their processing mechanisms are still under debate due
      to the lack of instrumentation at atomic resolution. Molecular modeling based
      computational approaches can shed light onto the atomic level details of gene
      delivery systems, thus provide valuable input that cannot be readily obtained
      with experimental techniques. Here, we review the molecular modeling research
      pursued on critical gene therapy steps, highlight the knowledge gaps in the field
      and providing future perspectives. Existing modeling studies revealed several
      important aspects of gene delivery, such as nanoparticle formation dynamics with
      various carriers, effect of carrier properties on complexation, carrier
      conformations in endosomal stages, and release of polynucleotides from carriers.
      Rate-limiting steps related to cellular events (i.e. internalization, endosomal
      escape, and nuclear uptake) are now beginning to be addressed by computational
      approaches. Limitations arising from current computational power and accuracy of
      modeling have been hindering the development of more realistic models. With the
      help of rapidly-growing computational power, the critical aspects of gene therapy
      are expected to be better investigated and direct comparison between more
      realistic molecular modeling and experiments may open the path for design of next
      generation gene therapeutics.

PMID- 24856109
TI  - Regulation of the endothelialization by human vascular endothelial cells by
      ZNF580 gene complexed with biodegradable microparticles.
AB  - The lack of living endothelial cells (ECs) functional layer is one of the major
      reasons which account for thrombosis of synthetic vascular vessels. To overcome
      this obstacle, we employed ZNF580 gene complexed with biodegradable
      microparticles (MPs) to promote the rapid endothelialization by ECs. In order to
      realize the controlled release of ZNF580 gene from MPs/gene complexes, a series
      of amphiphilic triblock copolymers with different degradation rate, namely,
      methoxy-poly(ethylene glycol)-block-poly(3(S)-methyl-morpholine-2,5-dione)-graft
      polyethyleneimine (mPEG-b-PMMD-g-PEI), methoxy-poly(ethylene glycol)-block
      poly(3(S)-methyl-morpholine-2,5-dione-co-lactide)-graft-polyethyleneimine (mPEG-b
      P(MMD-co-LA)-g-PEI) and methoxy-poly(ethylene glycol)-block-poly(3(S)-methyl
      morpholine-2,5-dione-co-lactide-co-glycolide)-graft-polyethyleneimine (mPEG-b
      P(MMD-co-LA-co-GA)-g-PEI), were synthesized. Then, MPs were formed by self
      assembly. The hydrophobic cores of these MPs were composed of PMMD, P(MMD-LA) or
      P(MMD-co-LA-co-GA) segments, and provided crosslinking points for numbers of PEG
      and short PEI chains to form a high hydrophilic and positive charged corona/shell
      structure. Based on their positive charged surface, MPs can compact pEGFP-ZNF580
      into MPs/pEGFP-ZNF580 complexes. The cell transfection result demonstrated that
      pEGFP-ZNF580 could be transported efficiently into ECs by these complexes. The
      result of western blot showed that the relative ZNF580 protein level can increase
      to 35.74%-46.11% by the overexpression of ZNF580 gene. Furthermore, the release
      of pEGFP-ZNF580 could be sustained at least 25 days due to the controllable
      degradation ability of the hydrophobic MPs' core. The MPs and MPs/pEGFP-ZNF580
      complexes showed low cytotoxicity because of the introduction of PEG chains and
      low molecular weight PEI on the surface of these MPs. Notably, at the low
      concentration (20 MUg/mL), the MPs and their complexes were non-cytotoxicity. The
      rapid endothelialization was promoted significantly by the expression of pEGFP
      ZNF580.

PMID- 24856111
TI  - Lathyrane-type diterpenoids from the seeds of Euphorbia lathyris.
AB  - Ten lathyrane-type diterpenoids named Euphorbia Factor L12-L21 (1-10) and twelve
      known diterpenoids (11-22) were isolated from seeds of Euphorbia lathyris. The
      structures of these compounds were determined by extensive spectroscopic (UV, IR,
      HRESIMS, 1D and 2D NMR) analyses. In addition, the configuration of Euphorbia
      Factor L12 (1) was further confirmed by X-ray crystallographic and circular
      dichroism (CD) analyses. A putative biogenetic relationship to these compounds
      was proposed. Cytotoxicity of the isolated compounds against C6 and MCF-7 cell
      lines were evaluated. Compounds 1, 5, 7, 12 and 17 exhibited considerable
      cytotoxic activities (IC50 12.4-36.2 MUM).

PMID- 24856112
TI  - Blue light-promoted rice leaf bending and unrolling are due to up-regulated
      brassinosteroid biosynthesis genes accompanied by accumulation of castasterone.
AB  - In this study the relationship between blue light- and brassinosteroid-enhanced
      leaf lamina bending and unrolling in rice was investigated. Twenty-four hours (h)
      irradiation with white or blue light increased endogenous brassinosteroid levels,
      especially those of typhasterol and castasterone, in aerial tissues of rice
      seedlings. There was an accompanying up-regulation of transcript levels of
      CYP85A1/OsDWARF, encoding an enzyme catalyzing C-6 oxidation, after 6h under
      either white or blue light. These effects were not observed in seedlings placed
      under far-red or red light regimes. It was concluded that blue light up-regulates
      the levels of several cytochrome P450 enzymes including CYP85A1, thereby
      promoting the synthesis of castasterone, a biologically active brassinosteroid in
      rice. Based on these findings, it is considered that blue light-mediated rice
      leaf bending and unrolling are consequences of the enhanced biosynthesis of
      endogenous castasterone. In contrast to aerial tissues, brassinosteroid synthesis
      in roots appeared to be negatively regulated by white, blue and red light but
      positively controlled by far-red light. 

PMID- 24856110
TI  - Functions of caspase 8: the identified and the mysterious.
AB  - Initially discovered as an initiator protease in apoptosis mediated by death
      receptors, caspase-8 is now known to have an apparently confounding opposing
      effect in securing cell survival. It is required to allow mouse embryo survival,
      and the survival of hematopoietic cells during their development and activation.
      Classic models in which caspase-8 is depleted or inhibited frequently result in
      inhibition of apoptosis, and conversion to death through a necrotic pathway. This
      bewildering switch is now known to be driven by activation of a pathway dependent
      on protein kinases of the RIP family, which engage a pathway known as
      necroptosis. If caspase-8 does not control this pathway, necrotic death results.
      The pro-apoptotic and pro-survival functions of caspase-8 are regulated by a
      specific interaction with the pseudo-caspase cFLIP, and it is thought that the
      heterocomplex between these two partners alters the substrate specificity of
      caspase-8 in favor of inactivating components of the RIP kinase pathway. The
      description of how caspase-8 and cFLIP coordinate the switch between apoptosis
      and survival is just beginning. The mechanism is not known, the differential
      targets are not known, and the reason of why an apoptotic initiator has been co
      opted as a critical survival factor is only guessed at. Elucidating these
      unknowns will be important in understanding mechanisms and possible therapeutic
      targets in autoimmune, inflammatory, and metastatic diseases. 

PMID- 24856113
TI  - Outbreak among healthy newborns due to a new variant of USA300-related meticillin
      resistant Staphylococcus aureus.
AB  - BACKGROUND: The prevalence of community-associated meticillin-resistant
      Staphylococcus aureus (CA-MRSA) is increasing throughout the world and is an
      important cause of skin and soft tissue infection (SSTI) in children and
      neonates. AIM: To describe the successful control of an outbreak caused by a new
      strain of CA-MRSA in a newborn nursery. METHODS: The investigation of the
      outbreak in July 2012 is reported with the control measures taken. Molecular
      typing of the MRSA isolates was performed. FINDINGS: An outbreak of SSTI caused
      by CA-MRSA occurred in a newborn nursery. Six neonates were infected in a one
      month period [infection rate: 8.5% (6/71)]. A new variant of CA-MRSA was
      responsible, which was characterized as USA300-related, Panton-Valentine
      Leucocidin (PVL) positive, arginine catabolic mobile element (ACME) negative,
      sequence type 8 (ST8), staphylococcal cassette chromosome mec (SCCmec) type IVa,
      agr type I and spa type t008. The outbreak among term neonates followed a rapid
      transmission pattern and was successfully controlled by implementing various
      outbreak control measures, including universal chlorhexidine bathing. CONCLUSION:
      This is the first report of a hospital outbreak caused by a USA300-related CA
      MRSA clone in Korea. Early recognition and reinforcement of infection control
      measures are important in decreasing transmission of CA-MRSA in a hospital
      setting.

PMID- 24856114
TI  - Comparison of intensive-care-unit-acquired infections and their outcomes among
      patients over and under 80 years of age.
AB  - BACKGROUND: Patients aged >80 years represent a growing population admitted to
      intensive care units (ICUs). However, little is known about ICU-acquired
      infection (IAI) in this population, and the rate of invasive procedures is
      increasing. AIM: To evaluate the frequency and effects of IAI in elderly (>=80
      years) and younger patients. METHODS: Retrospective evaluation of consecutive
      patients hospitalized for three days or more over a three-year period in an 18
      bed ICU in an academic medical centre. FINDINGS: Elderly patients represented
      18.9% of the study population. At admission, the mean number of organ
      dysfunctions was similar in elderly and younger patients. The use of invasive
      procedures was also similar in elderly and younger patients, as follows: invasive
      mechanical ventilation for more than two days, 67.4% vs 55%; central venous
      catheterization, 56.9% vs 51.4%; and renal replacement therapy, 17.6% vs 17.8%,
      respectively. The frequency of IAI was 16.5% in elderly patients and 13.9% in
      younger patients (P = 0.28), with 20.5 vs 18.9 IAI episodes per 1000 ICU-days,
      respectively (P = 0.2). A Cox model identified central venous catheterization and
      invasive mechanical ventilation for more than two days as independent risk
      factors for IAI. The associations between IAI and prolonged ICU stay, increased
      nursing workload, and ICU and hospital mortality rates were similar in elderly
      and younger patients. CONCLUSIONS: The frequency of IAI was similar in elderly
      and younger patients, as were the associations between IAI and length of ICU
      stay, nursing workload and ICU mortality in an ICU with a high rate of invasive
      procedures.

PMID- 24856115
TI  - Validity analysis of a unique infection surveillance system in the intensive care
      unit by analysis of a data warehouse built through a workflow-integrated software
      application.
AB  - BACKGROUND: An electronic decision support programme was developed within the
      intensive care unit (ICU) that provides an overview of all infection-related
      patient data, and allows ICU physicians to add clinical information during
      patient rounds, resulting in prospective compilation of a database. AIM: To
      assess the validity of computer-assisted surveillance (CAS) of ICU-acquired
      infection performed by analysis of this database. METHODS: CAS was compared with
      prospective paper-based surveillance (PBS) for ICU-acquired respiratory tract
      infection (RTI), bloodstream infection (BSI) and urinary tract infection (UTI)
      over four months at a 36-bed medical and surgical ICU. An independent panel
      reviewed the data in the case of discrepancy between CAS and PBS. FINDINGS: PBS
      identified 89 ICU-acquired infections (13 BSI, 18 UTI, 58 RTI) and CAS identified
      90 ICU-acquired infections (14 BSI, 17 UTI, 59 RTI) in 876 ICU admissions. There
      was agreement between CAS and PBS on 13 BSI (100 %), 14 UTI (77.8 %) and 42 RTI
      (72.4 %). Overall, there was agreement on 69 infections (77.5%), resulting in a
      kappa score of 0.74. Discrepancy between PBS and CAS was the result of capture
      error in 11 and 14 infections, respectively. Interobserver disagreement on
      probability (13 RTI) and focus (two RTI, one UTI) occurred for 16 episodes. The
      time required to collect information using CAS is less than 30% of the time
      required when using PBS. CONCLUSION: CAS for ICU-acquired infection by analysis
      of a database built through daily workflow is a feasible surveillance method and
      has good agreement with PBS. Discrepancy between CAS and PBS is largely due to
      interobserver variability.

PMID- 24856116
TI  - Preoperative chemoradiotherapy in locally advanced gastric cancer, a phase I/II
      feasibility and efficacy study.
AB  - OBJECTIVES: This study was initiated to investigate the feasibility and efficacy
      of preoperative radiotherapy with weekly paclitaxel and carboplatin in locally
      advanced gastric cancer. METHODS: In a prospective study, patients with locally
      advanced gastric cancer stage IB-IV(M0) were treated with chemoradiotherapy
      followed by surgery 4-6 weeks after the last irradiation. Chemoradiotherapy
      consisted of radiation to a total dose of 45 Gy given in 25 fractions of 1.8 Gy,
      combined with concurrent weekly carboplatin and paclitaxel. RESULTS: Between
      December 2007 and January 2012, 25 patients with cT3 (64%) or cT4 (36%) gastric
      cancer were included. One patient discontinued concurrent chemotherapy in the 4th
      week due to toxicity, but completed radiotherapy. Another patient discontinued
      chemoradiotherapy after the 3rd week due to progressive disease. Grade III
      adverse events of chemoradiotherapy were: gastrointestinal 12%, haematological
      12% and other 8%. All patients, except one who developed progressive disease,
      were operated. Surgical complications were: general/infectious 48%, anastomotic
      leakage 12%, and bowel perforation 8%. Postoperative mortality was 4%.
      Microscopically radical resection rate was 72%. Pathological complete response
      rate was 16% and near complete response rate 24%. CONCLUSIONS: In this study,
      preoperative chemoradiotherapy for patients with locally advanced gastric cancer
      was associated with manageable toxicity and encouraging pathological response
      rates.

PMID- 24856118
TI  - Percutaneous enzyme emulsification endarterectomy.

PMID- 24856117
TI  - Chemokines and chemokine receptors: update on utility and challenges for the
      clinician.

PMID- 24856119
TI  - Borderline resectable pancreatic cancer: a consensus statement by the
      International Study Group of Pancreatic Surgery (ISGPS).
AB  - BACKGROUND: This position statement was developed to expedite a consensus on
      definition and treatment for borderline resectable pancreatic ductal
      adenocarcinoma (BRPC) that would have worldwide acceptability. METHODS: An
      international panel of pancreatic surgeons from well-established, high-volume
      centers collaborated on a literature review and development of consensus on
      issues related to borderline resectable pancreatic cancer. RESULTS: The
      International Study Group of Pancreatic Surgery (ISGPS) supports the National
      Comprehensive Cancer Network criteria for the definition of BRPC. Current
      evidence supports operative exploration and resection in the case of involvement
      of the mesentericoportal venous axis; in addition, a new classification of
      extrahepatic mesentericoportal venous resections is proposed by the ISGPS.
      Suspicion of arterial involvement should lead to exploration to confirm the
      imaging-based findings. Formal arterial resections are not recommended; however,
      in exceptional circumstances, individual therapeutic approaches may be evaluated
      under experimental protocols. The ISGPS endorses the recommendations for specimen
      examination and the definition of an R1 resection (tumor within 1 mm from the
      margin) used by the British Royal College of Pathologists. Standard preoperative
      diagnostics for BRPC may include: (1) serum levels of CA19-9, because CA19-9
      levels predict survival in large retrospective series; and also (2) the modified
      Glasgow Prognostic Score and the neutrophil/lymphocyte ratio because of the
      prognostic relevance of the systemic inflammatory response. Various regimens of
      neoadjuvant therapy are recommended only in the setting of prospective trials at
      high-volume centers. CONCLUSION: Current evidence justifies portomesenteric
      venous resection in patients with BRPC. Basic definitions were identified, that
      are currently lacking but that are needed to obtain further evidence and
      improvement for this important patient subgroup. A consensus for each topic is
      given.

PMID- 24856120
TI  - Impact of prophylactic central compartment neck dissection on locoregional
      recurrence of differentiated thyroid cancer in clinically node-negative patients:
      a retrospective study of a large clinical series.
AB  - BACKGROUND: In clinically node-negative patients with differentiated thyroid
      cancer (DTC), indications for routine central lymph node dissection (RCLD) are
      the subject of intensive research, and surgeons are divided between the pros and
      cons of this surgery. To better define the role of neck dissection in the
      treatment of DTC, we analyzed retrospectively the results in three centers in
      Italy. METHODS: The clinical records of 752 clinically node-negative patients
      with DTC who underwent operative treatment between January 1998 and December 2005
      in three endocrine surgery referral units were evaluated retrospectively. The
      complications and medium- and long-term outcomes of total thyroidectomy (TT)
      alone (performed in 390 patients: group A) and TT combined with bilateral RCLD
      (362 patients: group B) were analyzed and compared. RESULTS: The incidence of
      permanent hypoparathyroidism and permanent unilateral vocal folds was 1% and 0.8%
      in group A and 3.6% and 1.7% in the group B, respectively. Bilateral temporary
      recurrent nerve palsy was observed in one of the 362 patients in group B. After a
      follow-up of 9.5 +/- 3.5 years (mean +/- SD), the locoregional recurrence rate
      with positive cervical lymph nodes was not substantially significantly different
      between the two groups. CONCLUSION: In our series, TT combined with bilateral
      RCLD was associated with a greater rate of transient and permanent complications.
      Similar incidences of locoregional recurrence were reported in the two groups of
      patients. Considering the recent trend toward routine central lymphadenectomy,
      further studies are needed to evaluate the benefits of these different
      approaches.

PMID- 24856121
TI  - Grit: a marker of residents at risk for attrition?
AB  - BACKGROUND: Attrition from general surgery residency remains constant at
      approximately 20% despite nearly a decade of work-hour reform and studies aiming
      to identify common risk factors. High rates of attrition from training have a
      wide impact, from the overall quality of trainees produced to implications on
      public health and the broader surgical work force. We set out to evaluate a novel
      character trait, grit, defined as passion and perseverance for long-term goals,
      as a marker and potential risk factor for resident attrition. METHODS: Twelve
      Accreditation Council for Graduate Medical Education-approved general surgery
      residency programs participated in a prospective, multi-institutional, survey
      based analysis of grit and attrition during the 2012-2013 academic year.
      Participating individuals were blinded with regards to the primary outcome of the
      study. Participating institutions were blinded to the responses of their
      trainees. Participating residency programs were located in a variety of settings,
      from university-based health systems to community hospitals. RESULTS: Sixty-eight
      percent (68%) of residents (180 of 265) at participating institutions completed
      the study. The primary end point for this study was attrition from residency as a
      function of grit. Secondary end points included an evaluation of the utility of
      the grit score in surgical residents, variability of grit according to
      postgraduate year, sex, measurements of resident satisfaction with current
      program, lifestyle, and career goals. Finally, the study included an analysis of
      key resident support strategies. The attrition rate across 12 institutions
      surveyed was approximately 2% (5 residents). Of those five, three participated in
      our study. All three had below-median levels of grit. Those residents with below
      median grit were more likely to contemplate leaving surgical residency. Given the
      low attrition rate, no variable surveyed reached statistical significance in our
      analysis. Key support strategies for residents responding included family,
      friends outside of residency, co-residents, and formal mentorship through their
      particular residency. CONCLUSION: In this preliminary underpowered study, grit
      appears to be a promising marker and risk factor for attrition from surgical
      residency. In an effort to retain residents, programs should consider screening
      for grit in current residents and directing support to those residents with below
      median values, with a focus on building family, friend, and formal mentor
      relationships.

PMID- 24856122
TI  - Unique patterns and proper management of postgastrectomy bleeding in patients
      with gastric cancer.
AB  - BACKGROUND: Bleeding after gastrectomy is a less frequent, but fatal
      complication. Because the pathophysiology and clinical manifestations differ
      considerably across cases, the exact outcome of postoperative bleeding is
      unclear. This study aimed to improve management practices for postgastrectomy
      bleeding by the analysis of risk factors and clinical patterns. METHODS: From
      January 2001 to December 2010, 5,739 patients underwent gastrectomy for gastric
      cancer at the National Cancer Center, Korea. Clinical data from patients with
      postoperative bleeding were obtained from a prospectively established database,
      and risk factors for bleeding were analyzed using multivariate binary logistic
      regression. RESULTS: Incidence of the postoperative bleeding was 0.8% (n = 48)
      and the subsequent mortality rate was 10% (5/48). Majority of anastomotic
      bleeding occurred early within 1 day of the operation (5/7; 71%). It was
      successfully managed with conservative treatment in 3 patients, endoscopic
      intervention in 2, and relaparotomy in 2. Arterial bleeding occurred in 24
      patients, with the main site being the splenic artery (11/24; 46%), and mostly
      manifested in the delayed period (median, 12 days). Fifteen of them underwent
      radiologic intervention, and 4 of these patients were referred for operation
      eventually. The other 9 patients underwent relaparotomy as first-line treatment.
      Independent risk factors for the bleeding were male (hazard ratio [HR] 2.253; 95%
      CI, 1.079-4.704), comorbidity (HR, 2.709; 95% CI, 1.440-5.095), previous
      abdominal operation (HR, 2.785; 95% CI, 1.322-5.867), and palliative surgery (HR,
      4.142; 95% CI, 1.443-11.889). CONCLUSION: Postgastrectomy bleeding can be managed
      properly considering its origin, severity, onset, and the risk factors.

PMID- 24856123
TI  - Insulin sensitivity is related to glycemic control in type 2 diabetes and
      diabetes remission after Roux-en Y gastric bypass.
AB  - BACKGROUND: After initial onset, adequate glycemic control in patients with type
      2 diabetes (T2DM) presents a continuing challenge even with aggressive
      pharmacologic treatment, and longer disease duration is associated with poorer
      resolution in response to Roux-en Y gastric bypass (RYGB). Skeletal muscle
      insulin sensitivity is an important determinant of glycemic control. We
      investigated whether skeletal muscle insulin sensitivity is predictive of T2DM
      resolution with RYGB and is in general lower in patients with longer-duration
      T2DM. METHODS: Insulin sensitivity (SI) and the acute response to glucose (AIRg)
      were calculated by MINMOD analysis from glucose and insulin obtained during a
      modified frequently sampled intravenous glucose tolerance test. RESULTS: Pre-RYGB
      SI and duration but not AIRg were predictive of T2DM resolution by RYGB. In
      addition, HbA1c was greater and SI and AIRg lower in long- (8+ years) compared
      with short-duration (1- to 7-year) T2DM. Multiple linear regression analysis
      demonstrated that SI explained 32% and AIRg 21% of the variance in HbA1c,
      respectively. CONCLUSION: The current results suggest that pre-RYGB SI is
      predictive of T2DM resolution after RYGB, skeletal muscle insulin sensitivity and
      beta-cell function worsen after the onset of T2DM, and low skeletal muscle
      insulin sensitivity as well as low beta cell function contribute to poor glycemic
      control in T2DM.

PMID- 24856124
TI  - Prospective evaluation of the correlation between torso height and aortic anatomy
      in respect of a fluoroscopy free aortic balloon occlusion system.
AB  - BACKGROUND: To report the lengths of key torso vascular and to develop regression
      models that will predict these lengths, based on an external measure of torso
      height (EMTH, sternum to pubis) in the development of a fluoroscopy-free balloon
      occlusion system for hemorrhage control. METHODS: We conducted a prospective,
      observational study at a Combat Support Hospital in Southern Afghanistan using
      adult male patients undergoing computed tomography (CT). EMTH was recorded using
      a tape measure and intra-arterial distance was derived from CT imaging.
      Regression models to predict distance from the common femoral artery (CFA) into
      the middle of aortic zone I (left subclavian artery to celiac trunk) and zone III
      (infrarenal aorta) were developed from a random 20% of the cohort and validated
      by the remaining 80%. RESULTS: Overall, 177 male patients were included with a
      median (interquartile range [IQR]) age of 23 (8) years. The median (IQR) lengths
      of aortic zone I and III were 222 (24), 31 (9), and 92 (15) mm. The mid-zone
      distance from the left and right CFA to zone I were 423 (27) and 418 (29) and for
      zone III 232 (21) and 228 (22). Linear regression models demonstrated an accuracy
      between 99.3% to 100% at predicting the insertion distance required to place a
      catheter within the middle of each aortic zone. CONCLUSION: This study
      demonstrates the use of morphometric analysis in the development of a fluoroscopy
      free balloon occlusion system for torso hemorrhage control. Further study in a
      larger population of mixed gender is required to further validate insertion
      models.

PMID- 24856125
TI  - Risk factors for colostomy in military colorectal trauma: a review of 867
      patients.
AB  - BACKGROUND: Limited data exist examining the use of fecal diversion in combatants
      from modern armed conflicts. Characterization of factors leading to colostomy
      creation is an initial step toward optimizing and individualizing combat casualty
      care. METHODS: A retrospective review of the US Department of Defense Trauma
      Registry database was performed for all US and coalition troops with colorectal
      injuries sustained during combat operations in Iraq and Afghanistan over 8 years.
      Colostomy rate, anatomic injury location, mechanism of injury, demographic data,
      and initial physiologic parameters were examined. Univariate and multivariate
      analyses were conducted. RESULTS: We identified 867 coalition military personnel
      with colorectal injuries. The overall colostomy rate was 37%. Rectal injuries had
      the highest diversion rate (56%), followed by left-sided (41%) and right-sided
      (20%) locations (P < .0001). Those with gunshot wounds (GSW) underwent diversion
      more often than blast injuries (43% vs 31% respectively, P < .0008). Injury
      Severity Score >=16 (41% vs 30%; P = .0018) and damage control surgery (DCS;
      48.2% vs 31.4%; P < .0001) were associated with higher diversion rates. On
      multivariate analysis, significant predictors for colostomy creation were injury
      location: Rectal versus left colon (odds ratio [OR], 2.2), rectal versus right
      colon (OR, 7.5), left versus right colon (OR, 3.4), GSW (OR, 2.0), ISS >= 16 (OR,
      1.7), and DCS (OR, 1.6). CONCLUSION: In this exploratory study of 320 combat
      related colostomies, distal colon and rectal injuries continue to be diverted at
      higher rates independent of other comorbidities. Additional outcomes-directed
      research is needed to determine whether such operative management is beneficial
      in all patients.

PMID- 24856126
TI  - Prognostic implication of mucinous histology in resected colorectal cancer liver
      metastases.
AB  - BACKGROUND: Colorectal mucinous adenocarcinoma (MAC) is a subtype of colorectal
      adenocarcinoma with prominent mucin production associated with proximal location
      of tumor, advanced stage at diagnosis, microsatellite instability, and BRAF
      mutation. The prognostic implication of MAC in colorectal cancer liver metastases
      (CRCLM) is unknown. The purpose of our study was to determine the frequency and
      elucidate the prognostic implication of mucinous histology in CRCLM. METHODS: The
      medical records of 118 patients who underwent CRCLM resection between 2000 and
      2010 were reviewed. Clinicopathologic variables and outcome parameters were
      examined. Resected specimens were submitted to routine histologic evaluation.
      Patients were grouped according to the metastasis mucinous content: >50%, MAC;
      <50%, adenocarcinoma with intermediated mucinous component (AIM); and without any
      mucinous component, non-MAC (NMA). RESULTS: Mean follow-up after resection was 37
      months. Tumor recurrence was observed in 75% of patients. Overall survival and
      disease-free survival rates after hepatectomy were 61%, 56%, and 26%, 24% at 3
      and 5 years, respectively. Tumors with mucinous component (AIM and MAC) were
      related to proximal location of the primary tumor and were more frequently
      observed in females. Multivariate analysis revealed that MAC was an independent
      negative prognostic factor (hazard ratio, 3.13; 95% CI, 1.30-6.68; P = .011)
      compared with non-MAC (NMA and AIM). CONCLUSION: MAC has an adverse prognostic
      impact compared with NMA, which may influence therapeutic strategy raising an
      important subject for discussion and future investigation.

PMID- 24856128
TI  - Cost-utility analysis of repair of reducible ventral hernia.
AB  - BACKGROUND: Patient-reported outcomes are an important metric of the
      effectiveness of care. Ventral hernia repair is a procedure where the
      effectiveness can best be quantified using health-related quality of life. This
      study sought to quantify quality of life with respect to costs of ventral hernia
      repair. METHODS: This observational study of patients diagnosed with a ventral
      hernia between 2004-2011 in a single center identified 3 groups of patients: (1)
      Patients diagnosed with ventral hernias managed with observation, (2) patients
      diagnosed with ventral hernias who underwent operative repair only when
      incarceration occurred, and (3) patients with ventral hernias who underwent
      herniorraphy before incarceration. The Short Form (SF)12v2 was administered to
      measure quality of life. The direct costs of care were obtained from Financial
      Services. Patients were surveyed about direct, non-health costs to obtain a
      societal perspective. A cost-utility analysis was performed. RESULTS: The SF-12v2
      was administered to 243 patients; 80 were observed, 69 underwent repair of an
      incarcerated hernia, and 94 underwent repair of a nonincarcerated hernia. The
      response rates were similar among groups-59%, 55%, and 52%. Quality of life as
      measured by utility score was less at 0.68 (95% CI, 0.65-0.71) in patients who
      did not undergo repair compared with those after repair of a nonincarcerated
      hernia, 0.76 (95% CI, 0.73-0.79; P < .001). The elective repair of a
      nonincarcerated hernia was cost-effective with an incremental cost effectiveness
      ratio of $8,646 per quality-adjusted life-year. CONCLUSION: The prompt elective
      repair of ventral hernias is cost-effective.

PMID- 24856129
TI  - Francesco Durante and the hospital "Policlinico Umberto I": the idea of a
      multidisciplinary university hospital.

PMID- 24856127
TI  - Heparin-binding epidermal growth factor-like growth factor restores Wnt/beta
      catenin signaling in intestinal stem cells exposed to ischemia/reperfusion
      injury.
AB  - BACKGROUND: We have previously demonstrated that heparin-binding epidermal growth
      factor (EGF)-like growth factor (HB-EGF) protects the intestines from injury in
      several different experimental animal models. In the current study, we
      investigated whether the ability of HB-EGF to protect the intestines from
      ischemia/reperfusion (I/R) injury was related to its effects on Wnt/beta-catenin
      signaling in intestinal stem cells (ISC). METHODS: Lucien-rich repeat-containing
      G-protein-coupled receptor 5 (LGR5)-enhanced green fluorescent protein (EGFP)
      transgenic (TG) mice with fluorescently labeled ISC, as well as the same mice
      treated with intraluminal HB-EGF or genetically engineered to overexpress HB-EGF,
      were exposed to segmental mesenteric artery occlusion (sMAO) to the terminal
      ilium. Wnt/beta-catenin signaling was evaluated using immunofluorescent staining
      and Western blotting. RESULTS: LGR5 expression and Wnt/beta-catenin signaling in
      the ISC of the terminal ilium of LGR5-EGFP TG mice was significantly reduced 24
      hours after sMAO. Intraluminal administration of HB-EGF or HB-EGF overexpression
      in these mice led to preservation of LGR5 expression and Wnt/beta-catenin
      signaling. CONCLUSION: These data show that HB-EGF preserves Wnt/beta-catenin
      signaling in ISC after I/R injury.

PMID- 24856130
TI  - Parents with intellectual disabilities seeking professional parenting support:
      the role of working alliance, stress and informal support.
AB  - Delaying or refraining from seeking advice and support in difficult parenting
      situations is identified as an important risk factor for child abuse and neglect.
      This study tested whether the extent of delays in support seeking is associated
      with working alliance for parents with mild intellectual disabilities (MID) and
      whether the importance of working alliance may depend on parenting stress and
      availability of informal support. Delays in support seeking were measured as
      parental latency (time waited) to approach the support worker. This latency was
      assessed in the intended response to hypothetical situations (vignettes) and in
      the reported behavioral response to real life difficult parenting situations from
      the preceding weeks. Multiple regression analyses were conducted for testing main
      and interaction effects of predictors on latency for support seeking. Better
      quality of the working alliance was associated with shorter intended latency to
      seek support for parents with MID, if parents had little access to informal
      support. Higher parenting stress predicted a shorter latency for intended support
      seeking. Parental support seeking intentions were positively associated with
      support seeking behavior. A good quality of the working alliance might be
      important to connect needs of parents with MID to resources that professional
      support can offer, in particular for the most vulnerable parents. Parental
      reluctance to seek professional support may be the result of a combination of
      risk and protective factors and is not always a sign of poor working alliance.
      Implications for risk assessment and support practice are discussed. 

PMID- 24856131
TI  - Understanding the mediating role of corporal punishment in the association
      between maternal stress, efficacy, co-parenting and children's adjustment
      difficulties among Arab mothers.
AB  - This study, guided by the Family Systems Theory, examines the direct effect of
      maternal use of corporal punishment on children's adjustment difficulties. Also,
      it explores whether corporal punishment serves as a mediating factor in the
      relationship between several maternal characteristics, marital relationships, and
      children's adjustment difficulties. A total of 2,447 Arab mothers completed
      anonymous, structured, self-report questionnaires. The use of corporal punishment
      was generally strongly supported by the Arab mothers in our sample. A greater
      likelihood of using corporal punishment was found among mothers of boys rather
      than girls, among mothers with lower perceived self-efficacy to discipline
      children, and among mothers with a lower perception of their husbands'
      participation in child-related labor. In addition, the higher a mother's reports
      on disagreement with her husband about discipline methods and the stronger her
      level of maternal stress, the more likely she was to use corporal punishment.
      Corporal punishment also mediated the association between the above mentioned
      factors and child adjustment difficulties. Furthermore, a husband's emotional
      support and family socioeconomic status were directly associated to children's
      adjustment difficulties. The results of the current study emphasize the need to
      observe children's development within the context of their family systems and to
      consider the mutual influences of different subsystems such as marital
      relationships and mother-child interactions. Prevention and intervention programs
      should raise parents' awareness concerning the harmful effects of corporal
      punishment and take into account the impact of dynamic transactions of parental
      conflicts and disagreements regarding discipline methods on child outcomes. 

PMID- 24856132
TI  - Increasing of temperature induces pathogenicity of Streptococcus agalactiae and
      the up-regulation of inflammatory related genes in infected Nile tilapia
      (Oreochromis niloticus).
AB  - Temperature strongly affects the health of aquatic poikilotherms. In Nile tilapia
      (Oreochromis niloticus), elevated water temperatures increase the severity of
      streptococcosis. Here we investigated the effects of temperature on the
      vulnerability and inflammatory response of Nile tilapia to Streptococcus
      agalactiae (Group B streptococci; GBS). At 35 and 28  degrees C, GBS took 4 and
      7h, respectively to reach the log-phase and, when incubated with tilapia whole
      blood, experienced survival rates of 97% and 2%, respectively. The hemolysis
      activity of GBS grown at 35  degrees C was five times higher than that of GBS
      grown at 28  degrees C. GBS expressed cylE (beta-hemolysin/cytolysin), cfb (CAMP
      factor) and PI-2b (pili-backbone) much more strongly at 35  degrees C than at 28 
      degrees C. Challenging Nile tilapia reared at 35 and 28  degrees C with GBS
      resulted in accumulated mortalities of about 85% and 45%, respectively. At 35 
      degrees C, infected tilapia exhibited tremendous inflammatory responses due to a
      dramatic up-regulation (30-40-fold) of inflammatory-related genes (cyclooxygenase
      2, IL-1beta and TNF-alpha) between 6 and 96 h-post infection. These results
      suggest that the increase of GBS pathogenicity to Nile tilapia induced by
      elevated temperature is associated with massive inflammatory responses, which may
      lead to acute mortality.

PMID- 24856133
TI  - Evaluation of lamb and calf responses to Rift Valley fever MP-12 vaccination.
AB  - Rift Valley fever (RVF) is an important viral disease of animals and humans in
      Africa and the Middle East that is transmitted by mosquitoes. The disease is of
      concern to international agricultural and public health communities. The RVFV MP
      12 strain has been the most safety tested attenuated vaccine strain; thus it is
      being considered as a potential vaccine for the US national veterinary stockpile.
      This study was designed to establish safety protocols for large animal research
      with virulent RVF viruses, establish a target host immune response baseline using
      RVF MP-12 strain, and independently evaluate this strain as a potential US
      emergency response vaccine. Ten, approximately four month-old lambs and calves
      were vaccinated with RVF MP-12 strain; two additional animals per species
      provided negative control specimens. The animals were monitored for clinical and
      immune response, fever, and viremia. Two animals per species were sacrificed on
      2, 3, 4, 10 and 28 days post infection and full necropsies were performed for
      histopathological examination. No clinical or febrile responses were observed in
      this study. The onset and titer of the immune response is discussed. There was no
      significant histopathology in the lambs; however, 6 out of 10 vaccinated calves
      had multifocal, random areas of hepatocellular degeneration and necrosis. RVF
      MP12 antigen was detected in these areas of necrosis by immunohistochemistry in
      one calf. This study provides independent and baseline information on the RVF MP
      12 attenuated vaccination in vaccine relevant age target species and indicates
      the importance of performing safety testing on vaccine relevant aged target
      animals. 

PMID- 24856134
TI  - Phosphorylcholine and SpaA, a choline-binding protein, are involved in the
      adherence of Erysipelothrix rhusiopathiae to porcine endothelial cells, but this
      adherence is not mediated by the PAF receptor.
AB  - A crucial event in the initiation of many bacterial infections is the adherence
      of the bacteria to host cells, and bacterial surface structures and their
      interactions with host cell receptors play an important role in this process.
      Erysipelothrix rhusiopathiae is the causative agent of swine erysipelas, which
      may cause acute septicemia or chronic endocarditis and polyarthritis. To study
      the pathogenic mechanism of the widespread vascular disease observed in the acute
      form of swine erysipelas, we investigated the role of phosphorylcholine (PCho), a
      component of the E. rhusiopathiae capsule, in bacterial adherence to porcine
      endothelial cells (PECs) in vitro. We found that adherence of E. rhusiopathiae
      strain Fujisawa to PECs was twice that of adherence to control COS-7 cells and
      that the adherence rates of PCho-defective mutants were approximately 30-50%
      lower than those of the Fujisawa strain. The adherence of the Fujisawa strain to
      COS-7 cells transfected with the porcine platelet-activating factor receptor
      (PAFR) gene, which encodes a G protein-coupled receptor that has been shown to
      directly bind to Streptococcus pneumoniae via PCho in the bacterial cell wall,
      was not enhanced. Treatment with a PAFR antagonist (WEB-2086) did not inhibit
      bacterial adherence to PECs. Incubation of the bacterial cells with an antibody
      against PCho or SpaA, a choline-binding protein anchored to PCho of the Fujisawa
      strain, reduced the adherence of the strain to PECs. This effect was not observed
      when PCho-defective mutants were used. These results suggest that E.
      rhusiopathiae adheres to PECs via PCho and SpaA and that the PCho-mediated
      adherence is independent of PAFR. 

PMID- 24856135
TI  - Molecular and biochemical characterization of caffeine synthase and purine
      alkaloid concentration in guarana fruit.
AB  - Guarana seeds have the highest caffeine concentration among plants accumulating
      purine alkaloids, but in contrast with coffee and tea, practically nothing is
      known about caffeine metabolism in this Amazonian plant. In this study, the
      levels of purine alkaloids in tissues of five guarana cultivars were determined.
      Theobromine was the main alkaloid that accumulated in leaves, stems,
      inflorescences and pericarps of fruit, while caffeine accumulated in the seeds
      and reached levels from 3.3% to 5.8%. In all tissues analysed, the alkaloid
      concentration, whether theobromine or caffeine, was higher in young/immature
      tissues, then decreasing with plant development/maturation. Caffeine synthase
      activity was highest in seeds of immature fruit. A nucleotide sequence (PcCS) was
      assembled with sequences retrieved from the EST database REALGENE using sequences
      of caffeine synthase from coffee and tea, whose expression was also highest in
      seeds from immature fruit. The PcCS has 1083bp and the protein sequence has
      greater similarity and identity with the caffeine synthase from cocoa (BTS1) and
      tea (TCS1). A recombinant PcCS allowed functional characterization of the enzyme
      as a bifunctional CS, able to catalyse the methylation of 7-methylxanthine to
      theobromine (3,7-dimethylxanthine), and theobromine to caffeine (1,3,7
      trimethylxanthine), respectively. Among several substrates tested, PcCS showed
      higher affinity for theobromine, differing from all other caffeine synthases
      described so far, which have higher affinity for paraxanthine. When compared to
      previous knowledge on the protein structure of coffee caffeine synthase, the
      unique substrate affinity of PcCS is probably explained by the amino acid
      residues found in the active site of the predicted protein. 

PMID- 24856136
TI  - Nitric oxide and histone acetylation-shaping craniofacial development.
AB  - Previous work linked nitric oxide (NO) signaling to histone deacetelyases (HDACs)
      in the control of tissue homeostasis and suggested that deregulation of this
      signaling contributes to human diseases. In the previous issue of Chemistry &
      Biology, Kong and colleagues showed that coordinated NO signaling and histone
      acetylation are required for proper cranial neural crest development and
      craniofacial morphogenesis and suggested that alterations of NO/acetylation
      network can contribute to the pathogenesis of craniofacial malformations. 

PMID- 24856137
TI  - Bypassing AMPK phosphorylation.
AB  - AMP-activated protein kinase (AMPK) functions as a signaling hub to balance
      energy supply with demand. Phosphorylation of activation loop Thr172 has been
      considered as an essential step in AMPK activation. In this issue of Chemistry &
      Biology, Scott and colleagues show that the small molecule direct AMPK activator,
      A-769662, bypasses this phosphorylation event and acts synergistically with AMP
      on naive AMPK. 

PMID- 24856138
TI  - Modulating noncatalytic function with kinase inhibitors.
AB  - In this issue of Chemistry & Biology, Hari and colleagues show that conformation
      selective ATP-competitive kinase inhibitors have distinct noncatalytic effects on
      Erk2, including the ability to modulate protein-protein interactions outside the
      ATP-binding site. These findings enhance our knowledge about the diverse array of
      activities in which kinase inhibitors can target signaling pathways. 

PMID- 24856139
TI  - Polarity factors play a role in antibiotic resistance.
AB  - In this issue of Chemistry & Biology, Kirkpatrick and Viollier describe a new
      twist in the relationship between bacterial cell development and antibiotic
      resistance. They reveal that TipN, which orchestrates development at cell poles,
      is required to tolerate induced expression of an antibiotic efflux pump. 

PMID- 24856142
TI  - Overlapping MERS and mild AESD caused by HHV-6 infection.
AB  - We report the case of an overlapping encephalopathy syndrome consisting of
      clinically mild encephalitis/encephalopathy with a reversible splenial lesion
      (MERS) and a mild form of acute encephalopathy with biphasic seizures and late
      reduced diffusion (AESD) caused by human herpesvirus-6. A previously healthy 17
      month-old girl was admitted to our hospital as a precaution because of seizures
      that had developed more than 25 hours (h) after fever. Brain diffusion-weighted
      images (DWI) showed high signal intensity in the central splenial region on Day
      2. She regained consciousness 16 h after the second seizure. On Day 6, she had a
      secondary cluster of partial seizures. DWI showed resolution of the splenial
      lesion and revealed reduced diffusion in the fronto-subcortical white matter. She
      regained consciousness 36 h after the secondary cluster of seizures without any
      sequelae. A third DWI performed on Day 15 showed that the fronto-subcortical
      white matter lesions had completely disappeared. Based on the clinicoradiological
      findings, we diagnosed the patient with overlapping MERS and mild AESD. Our case,
      together with previous reports, suggests that patients can develop combined
      encephalopathy syndromes as a phenotype. Many encephalopathy syndromes have been
      established and classified; however, some may not present as independent
      syndromes.

PMID- 24856143
TI  - The role of the IL-22/IL-22R1 axis in cancer.
AB  - Interleukin-22 (IL-22) is an IL-10 family cytokine produced by T cells and innate
      lymphoid cells. The IL-22 signaling pathway orchestrates mucosal immune defense
      and tissue regeneration through pleiotropic effects including pro-survival
      signaling, cell migration, dysplasia and angiogenesis. While these functions can
      prevent initial establishment of tumors, they can also be hijacked by aggressive
      cancers to enhance tumor growth and metastasis. Thus, the role of the IL-22/IL
      22R1 axis in cancer is complex and context-specific. Evidence of IL-22
      involvement manifests as dysregulation of IL-22 expression and signaling in
      patients with many common cancers including those of the gut, skin, lung and
      liver. Unlike other cancer-associated cytokines, IL-22 has restricted tissue
      specificity as its unique receptor IL-22R1 is exclusively expressed on epithelial
      and tissue cells, but not immune cells. This makes it an attractive target for
      therapy as there is potential achieve anti-tumor immunity with fewer side
      effects. This review summarizes current findings on functions of IL-22 in
      association with general mechanisms for tumorigenesis as well as specific
      contributions to particular cancers, and ponders how best to approach further
      research in the field. 

PMID- 24856141
TI  - Mutation in TOR1AIP1 encoding LAP1B in a form of muscular dystrophy: a novel gene
      related to nuclear envelopathies.
AB  - We performed genome-wide homozygosity mapping and mapped a novel myopathic
      phenotype to chromosomal region 1q25 in a consanguineous family with three
      affected individuals manifesting proximal and distal weakness and atrophy, rigid
      spine and contractures of the proximal and distal interphalangeal hand joints.
      Additionally, cardiomyopathy and respiratory involvement were noted. DNA
      sequencing of torsinA-interacting protein 1 (TOR1AIP1) gene encoding lamina
      associated polypeptide 1B (LAP1B), showed a homozygous c.186delG mutation that
      causes a frameshift resulting in a premature stop codon (p.E62fsTer25). We
      observed that expression of LAP1B was absent in the patient skeletal muscle
      fibres. Ultrastructural examination showed intact sarcomeric organization but
      alterations of the nuclear envelope including nuclear fragmentation, chromatin
      bleb formation and naked chromatin. LAP1B is a type-2 integral membrane protein
      localized in the inner nuclear membrane that binds to both A- and B-type lamins,
      and is involved in the regulation of torsinA ATPase. Interestingly, luminal
      domain-like LAP1 (LULL1)-an endoplasmic reticulum-localized partner of torsinA
      was overexpressed in the patient's muscle in the absence of LAP1B. Therefore, the
      findings suggest that LAP1 and LULL1 might have a compensatory effect on each
      other. This study expands the spectrum of genes associated with nuclear
      envelopathies and highlights the critical function for LAP1B in striated muscle. 

PMID- 24856144
TI  - Cricothyroid muscle and thyroarytenoid muscle dominance in vocal register
      control: preliminary results.
AB  - HYPOTHESIS: Headmix and head registers use cricothyroid (CT) muscle dominant
      voicing, whereas chest and chestmix registers use thyroarytenoid (TA) muscle
      dominant voicing. STUDY DESIGN: Cross-sectional study. METHODS: CT and TA
      electromyographic data obtained from five untrained singers and two trained
      singers were analyzed to determine CT and TA muscle dominance as a function of
      register. Simultaneous recordings of TA and CT muscle activity and audio were
      obtained during production of pitch glides and a variety of midrange and upper
      pitches in chest, chestmix, headmix, and head registers. RESULTS: TA dominant
      phonation was only observed for chest productions and headmix/head register
      productions below 300 Hz. All phonation above 300 Hz, regardless of register,
      showed CT:TA muscle activity ratios that were CT dominant or close to 1,
      indicating nearly equal CT and TA muscle activity. This was true for all subjects
      on all vocal tasks. For the subjects sampled in this study, pitch level appeared
      to have a greater effect on TA and CT muscle dominance than vocal register.
      CONCLUSION: Preliminary findings regarding CT and TA dominance and register
      control do not support the assumption that all chest and chestmix production has
      greater TA muscle activity than CT muscle activity or that all headmix and head
      production require greater CT muscle activity than TA muscle activity. The data
      indicate that pitch level may play a greater role in determining TA and CT
      dominance than register.

PMID- 24856145
TI  - Supramolecular chiro-biomedical aspect of beta-blockers in drug development.
AB  - beta-Blockers are used globally for the treatment of cardiovascular problems.
      Unfortunately, these are consumed as racemic mixture causing serious side effects
      due to the presence of unwanted enantiomers. A simulation study of some commonly
      used beta-blockers was carried out at supramolecular level to understand stereo
      selective binding of beta-blockers with receptors (beta-ARs). The values of
      docking energy ranged from 6.58 to 9.11 and 7.05 to 9.15 kcal/mol for R- and S
      enantiomers, respectively. Mostly, S-enantiomers bind stronger with beta-ARs (in
      terms of docking energy) than their Rantipodes, with some exceptions. The results
      of docking study indicated higher pharmaceutical potencies of S-enantiomers than
      R-antipodes. 

PMID- 24856148
TI  - Pneumomediastinum and cervical subcutaneous emphysema caused by a perforated
      acute colonic diverticulitis.

PMID- 24856149
TI  - Iatrogenic perforation of the pulmonary artery by a pleural drain.

PMID- 24856150
TI  - Acute appendicitis in a patient with intestinal malrotation.

PMID- 24856151
TI  - Malignant rhabdoid tumor of the colon: a case report.

PMID- 24856152
TI  - Intention to use emergency contraceptive pills and the role of knowledge in a
      Dutch national sample.
AB  - OBJECTIVES: Emergency contraceptive pills (ECPs) are underused for preventing
      unintended pregnancy. Not all women are willing to use them even when at risk of
      conceiving. This paper examines whether increased knowledge about ECPs may
      increase the intention to use these products. METHODS: Factors associated with
      intention to use emergency contraception (EC) were assessed among 1310 women who
      participated in the nationally representative Sexual Health in the Netherlands
      2009 Survey. Logistic regression models included demographics, prior use of ECPs,
      and ECP knowledge. RESULTS: Seventeen percent of the women did not intend to use
      EC after unprotected sexual intercourse and a further 27% were unsure whether
      they would use it. Intention is most strongly related to prior use and not having
      children. Only two of six knowledge items were related to intention in the
      multivariate analyses. Being aware that ECPs can be obtained without prescription
      upgrades intention, whereas knowing that a woman can still get pregnant after
      having taken the ECP has a negative impact on intention. CONCLUSIONS: Improving
      knowledge may contribute to intention to use EC, but its role will be modest. To
      understand the reasons behind ECP use it is essential to study the contribution
      of other factors, like attitudes and social norms.

PMID- 24856155
TI  - Ceritinib for treatment of ALK-rearranged advanced non-small-cell lung cancer.
AB  - The anaplastic lymphoma kinase (ALK) gene plays a key role in the pathogenesis of
      selected tumors, including non-small-cell lung cancer (NSCLC). Patients with ALK
      rearranged NSCLC are initially sensitive to the ALK inhibitor crizotinib but
      eventually become resistant, limiting its therapeutic potential. Ceritinib is an
      oral second-generation ALK inhibitor with greater preclinical antitumor potency
      than crizotinib in ALK-positive NSCLC. A Phase I trial of ceritinib in ALK
      positive tumors demonstrated good activity in patients with advanced NSCLC,
      including those who had progressed on crizotinib. Adverse events are similar to
      those seen with other ALK tyrosine kinase inhibitors and are generally
      manageable. Ongoing trials are evaluating ceritinib in patients with ALK
      rearranged NSCLC treated with prior chemotherapy and/or crizotinib.

PMID- 24856154
TI  - Intrinsic conformational plasticity of native EmrE provides a pathway for
      multidrug resistance.
AB  - EmrE is a multidrug resistance efflux pump with specificity to a wide range of
      antibiotics and antiseptics. To obtain atomic-scale insight into the attributes
      of the native state that encodes the broad specificity, we used a hybrid of
      solution and solid-state NMR methods in lipid bilayers and bicelles. Our results
      indicate that the native EmrE dimer oscillates between inward and outward facing
      structural conformations at an exchange rate (k(ex)) of ~300 s(-1) at 37  degrees
      C (millisecond motions), which is ~50-fold faster relative to the
      tetraphenylphosphonium (TPP(+)) substrate-bound form of the protein. These
      observables provide quantitative evidence that the rate-limiting step in the
      TPP(+) transport cycle is not the outward-inward conformational change in the
      absence of drug. In addition, using differential scanning calorimetry, we found
      that the width of the gel-to-liquid crystalline phase transition was 2  degrees C
      broader in the absence of the TPP(+) substrate versus its presence, which
      suggested that changes in transporter dynamics can impact the phase properties of
      the membrane. Interestingly, experiments with cross-linked EmrE showed that the
      millisecond inward-open to outward-open dynamics was not the culprit of the
      broadening. Instead, the calorimetry and NMR data supported the conclusion that
      faster time scale structural dynamics (nanosecond-microsecond) were the source
      and therefore impart the conformationally plastic character of native EmrE
      capable of binding structurally diverse substrates. These findings provide a
      clear example how differences in membrane protein transporter structural dynamics
      between drug-free and bound states can have a direct impact on the physical
      properties of the lipid bilayer in an allosteric fashion.

PMID- 24856160
TI  - Adiposity and cardiovascular risk: a lifecourse perspective.

PMID- 24856162
TI  - Atelocollagen-mediated siRNA delivery: future promise for therapeutic
      application.

PMID- 24856161
TI  - Lifelong patterns of BMI and cardiovascular phenotype in individuals aged 60-64
      years in the 1946 British birth cohort study: an epidemiological study.
AB  - BACKGROUND: Excess body fat is associated with an increase in risk of type 2
      diabetes and hypertension in adulthood and these risks can adversely affect
      progression of arterial disease. We aimed to assess the impact of lifelong
      patterns of adiposity on cardiovascular risk factors and carotid intima media
      thickness (cIMT) in later life in participants in the 1946 British birth cohort
      study. METHODS: The National Survey of Health and Development Study was a
      nationally representative sample of 5362 singleton births to married parents in
      England, Scotland, and Wales, stratified by social class, during 1 week in March
      1946. Our present study is based on the 60% of participants still alive and with
      a known present address in England, Scotland, or Wales who attended a clinic
      assessment after invitation aged 60-64 years. We included participants with
      lifetime adiposity measures, cardiovascular risk factors, and cIMT measured at 60
      64 years. Participants were classified as normal weight or overweight or obese at
      each age (36, 43, 53, and 60-64 years) in adulthood, and childhood overweight was
      defined. Patterns of BMI change were identified and we used BMI to define
      adiposity status. We used multivariable linear regression to establish the cross
      sectional association of BMI category at age 60-64 years with cIMT, adjusted for
      various confounders. FINDINGS: We included 1273 (45%) of 2856 participants
      eligible in 2006-10 (at age 60-64 years) in this study. Compared with normal
      weight, overweight and obesity were associated with higher cIMT (0.029 mm, 95% CI
      0.014-0.043) and systolic blood pressure (7.95 mm Hg, 5.86-10.0). Increased cIMT,
      systolic blood pressure, leptin, prevalence of diabetes, and reduced adiponectin
      were all associated with duration of exposure to adult adiposity (p<0.0001 for
      all). We noted little additional effect of childhood overweight. Individuals who
      dropped a BMI category in adulthood had lower cIMT (-0.034 mm, -0.056 to -0.013)
      and leptin concentrations (-0.4 ng/mL, -0.47 to -0.32), even when this change was
      not maintained, than did those who never lost weight. INTERPRETATION: Longer
      exposure to high adiposity in adulthood had a cumulative adverse effect on
      cardiovascular phenotype in later life. Reductions in BMI category, even if not
      sustained, were associated with decreases in cIMT and improvements in
      cardiovascular risk-factor profile, suggesting that weight loss, at any age in
      adulthood, is worthwhile because it might result in long-term cardiovascular
      benefit. FUNDING: Medical Research Council and the British Heart Foundation.

PMID- 24856163
TI  - Can biologically inspired patches yield a new age of transdermal delivery?

PMID- 24856166
TI  - Interview with Daniel Kohane.
AB  - Dr Daniel S Kohane obtained his MD and a PhD in Physiology from Boston
      University. He subsequently completed residencies in pediatrics (Boston
      Children's Hospital) and anesthesiology (Massachusetts General Hospital),
      followed by a fellowship in pediatric critical care (Children's Hospital Boston).
      He is currently a Senior Associate in Pediatric Critical Care at Boston
      Children's Hospital, where he directs the Laboratory for Biomaterials and Drug
      Delivery. He is a Professor of Anesthesia at Harvard Medical School. 

PMID- 24856167
TI  - Flux through silicone and human skin fitted to a series/parallel model.
AB  - BACKGROUND: Recent reports of the good correlation between maximum flux through
      human skin in vitro from water, JMHAQ, and maximum flux through silicone from
      water, JMPAQ, demand that the mechanism of maximum flux across these two
      apparently quite different membranes be compared to understand the bases of the
      correlation. RESULTS/DISCUSSION: A n = 70 log JMPAQ database and a matched n = 55
      log JMHAQ database of molecules were found to fit well to a series/parallel model
      where three parallel solubility dependent pathways existed: a lipid pathway, an
      aqueous pathway, and a series pathway of alternating lipid and aqueous phases.
      CONCLUSION: The results of this analysis surprisingly suggest that the
      architecture of the two membranes present similar solubility based pathways
      through which drugs diffuse.

PMID- 24856168
TI  - Liposomal antibiotic formulations for targeting the lungs in the treatment of
      Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa is a Gram-negative bacterium that causes serious lung
      infections in cystic fibrosis, non-cystic fibrosis bronchiectasis,
      immunocompromised, and mechanically ventilated patients. The arsenal of
      conventional antipseudomonal antibiotic drugs include the extended-spectrum
      penicillins, cephalosporins, carbapenems, monobactams, polymyxins,
      fluoroquinolones, and aminoglycosides but their toxicity and/or increasing
      antibiotic resistance are of particular concern. Improvement of existing
      therapies against Pseudomonas aeruginosa infections involves the use of liposomes
      - artificial phospholipid vesicles that are biocompatible, biodegradable, and
      nontoxic and able to entrap and carry hydrophilic, hydrophobic, and amphiphilic
      molecules to the site of action. The goal of developing liposomal antibiotic
      formulations is to improve their therapeutic efficacy by reducing drug toxicity
      and/or by enhancing the delivery and retention of antibiotics at the site of
      infection. The focus of this review is to appraise the current progress of the
      development and application of liposomal antibiotic delivery systems for the
      treatment pulmonary infections caused by P. aeruginosa. 

PMID- 24856169
TI  - Penetrating the cell membrane, thermal targeting and novel anticancer drugs: the
      development of thermally targeted, elastin-like polypeptide cancer therapeutics.
AB  - Therapeutic peptides offer important cancer treatment approaches. Designed to
      inhibit oncogenes and other oncoproteins, early therapeutic peptides applications
      were hampered by pharmacokinetic properties now addressed through tumor targeting
      strategies. Active targeting with environmentally responsive biopolymers or
      macromolecules enhances therapeutics accumulation at tumor sites; passive
      targeting with macromolecules, or liposomes, exploits angiogenesis and poor
      lymphatic drainage to preferentially accumulate therapeutics within tumors.
      Genetically engineered, thermally-responsive, elastin-like polypeptides use both
      strategies and cell-penetrating peptides to further intratumoral cell uptake.
      This review describes the development and application of cell-penetrating peptide
      elastin-like polypeptide therapeutics for the thermally targeted delivery of
      therapeutic peptides. 

PMID- 24856170
TI  - Treatment of intermediate stage hepatocellular carcinoma: a review of
      intrahepatic doxorubicin drug-delivery systems.
AB  - The biopharmaceutical properties of doxorubicin delivered via two drug-delivery
      systems (DDSs) for the palliative treatment of unresectable hepatocellular
      carcinoma were reviewed with relation to the associated liver and tumor
      (patho)physiology. These two DDSs, doxorubicin emulsified with Lipiodol((r)) and
      doxorubicin loaded into DC Bead((r)) are different regarding tumor delivery,
      release rate, local bioavailability, if and how they can be given repeatedly,
      biodegradability, length of embolization and safety profile. There have been few
      direct head-to-head comparisons of these DDSs, and in-depth investigations into
      their in vitro and in vivo performance is warranted. 

PMID- 24856172
TI  - [Larva migrans cutaneous infection].

PMID- 24856173
TI  - [A 28-year-old man with hepatosplenomegaly and fever].

PMID- 24856174
TI  - Gastroenteritis outbreaks caused by a DS-1-like G1P[8] rotavirus strain, Japan,
      2012-2013.
AB  - Rotavirus A (RVA) genotype G1P[8], a hallmark of the Wa-like strain, typically
      contains only genotype 1 genes. However, an unusual RVA G1P[8] with genotype 2
      genes was recently detected in Japan. We determined the complete genomic
      constellation of this RVA. Our findings suggest that mixed RVAs may be more
      competitive than once thought. 

PMID- 24856175
TI  - Quantification of human growth hormone in serum with a labeled protein as an
      internal standard: essential considerations.
AB  - To manage and inform diagnostic or therapeutic decisions, measurement results
      which are accurate, specific, and comparable between laboratories are required.
      Two challenges associated with this are the definition of the measurand and the
      commutability of the reference standard used. Once the measurand is defined, the
      next step in improving standardization is developing traceable quantification
      methods for proteins in biological fluids. A novel reference method for the
      quantification of recombinant human growth hormone (rhGH) in serum has been
      developed using multistep sample cleanup at the protein level, tryptic digestion,
      and isotope dilution mass spectrometry (IDMS). Critical considerations for using
      isotopically labeled rhGH as the internal standard are described. A bulk serum
      sample was prepared at the clinically relevant level of 10 ng/g and quantified
      using the method described to give results traceable to the International System
      of Units (SI) with a total measurement uncertainty of <20%. Results compared
      favorably with an orthogonal traceable method using total tryptic digestion,
      peptide separation, and isotope dilution mass spectrometry. 

PMID- 24856176
TI  - In situ stability of substrate-associated cellulases studied by DSC.
AB  - This work shows that differential scanning calorimetry (DSC) can be used to
      monitor the stability of substrate-adsorbed cellulases during long-term
      hydrolysis of insoluble cellulose. Thermal transitions of adsorbed enzyme were
      measured regularly in subsets of a progressing hydrolysis, and the size of the
      transition peak was used as a gauge of the population of native enzyme. Analogous
      measurements were made for enzymes in pure buffer. Investigations of two
      cellobiohydrolases, Cel6A and Cel7A, from Trichoderma reesei, which is an
      anamorph of the fungus Hypocrea jerorina, showed that these enzymes were
      essentially stable at 25  degrees C. Thus, over a 53 h experiment, Cel6A lost
      less than 15% of the native population and Cel7A showed no detectable loss for
      either the free or substrate-adsorbed state. At higher temperatures we found
      significant losses in the native populations, and at the highest tested
      temperature (49  degrees C) about 80% Cel6A and 35% of Cel7A was lost after 53 h
      of hydrolysis. The data consistently showed that Cel7A was more long-term stable
      than Cel6A and that substrate-associated enzyme was less long-term stable than
      enzyme in pure buffer stored under otherwise equal conditions. There was no
      correlation between the intrinsic stability, specified by the transition
      temperature in the DSC, and the long-term stability derived from the peak area.
      The results are discussed with respect to the role of enzyme denaturation for the
      ubiquitous slowdown observed in the enzymatic hydrolysis of cellulose. 

PMID- 24856171
TI  - Mechanisms of microbubble-facilitated sonoporation for drug and gene delivery.

PMID- 24856177
TI  - Highly stereoselective synthesis of cyclopropylphosphonates catalyzed by chiral
      Ru(II)-Pheox complex.
AB  - Ru(II)-Pheox-catalyzed asymmetric cyclopropanation of diethyl
      diazomethylphosphonate with alkenes, including alpha,beta-unsaturated carbonyl
      compounds, afforded the corresponding optically active cyclopropylphosphonates in
      high yields and with excellent diastereoselectivity (up to 99:1) and
      enantioselectivity (up to 99% ee). 

PMID- 24856178
TI  - RNA self-assembly and RNA nanotechnology.
AB  - CONSPECTUS: Nanotechnology's central goal involves the direct control of matter
      at the molecular nanometer scale to build nanofactories, nanomachines, and other
      devices for potential applications including electronics, alternative fuels, and
      medicine. In this regard, the nascent use of nucleic acids as a material to
      coordinate the precise arrangements of specific molecules marked an important
      milestone in the relatively recent history of nanotechnology. While DNA served as
      the pioneer building material in nucleic acid nanotechnology, RNA continues to
      emerge as viable alternative material with its own distinct advantages for
      nanoconstruction. Several complementary assembly strategies have been used to
      build a diverse set of RNA nanostructures having unique structural attributes and
      the ability to self-assemble in a highly programmable and controlled manner. Of
      the different strategies, the architectonics approach uniquely endeavors to
      understand integrated structural RNA architectures through the arrangement of
      their characteristic structural building blocks. Viewed through this lens, it
      becomes apparent that nature routinely uses thermodynamically stable, recurrent
      modular motifs from natural RNA molecules to generate unique and more complex
      programmable structures. With the design principles found in natural structures,
      a number of synthetic RNAs have been constructed. The synthetic nanostructures
      constructed to date have provided, in addition to affording essential insights
      into RNA design, important platforms to characterize and validate the structural
      self-folding and assembly properties of RNA modules or building blocks.
      Furthermore, RNA nanoparticles have shown great promise for applications in
      nanomedicine and RNA-based therapeutics. Nevertheless, the synthetic RNA
      architectures achieved thus far consist largely of static, rigid particles that
      are still far from matching the structural and functional complexity of natural
      responsive structural elements such as the ribosome, large ribozymes, and
      riboswitches. Thus, the next step in synthetic RNA design will involve new ways
      to implement these same types of dynamic and responsive architectures into
      nanostructures functioning as real nanomachines in and outside the cell. RNA
      nanotechnology will likely garner broader utility and influence with a greater
      focus on the interplay between thermodynamic and kinetic influences on RNA self
      assembly and using natural RNAs as guiding principles.

PMID- 24856179
TI  - Is C-reactive protein a useful adjunct in selecting patients for emergency
      cholecystectomy by predicting severe/gangrenous cholecystitis?
AB  - Gangrenous cholecystitis is difficult to diagnose clinically and carries risk of
      morbidity and mortality if not treated urgently. Complex scoring systems exist to
      predict the condition. C reactive protein may be a single independent predictor
      as suggested in this small study. BACKGROUND: Gangrenous cholecystitis (GC) is a
      serious sequel of acute cholecystitis occurring in 2-30% patients and has a
      mortality of 0.2-0.5%. Urgent surgical intervention is important to reduce
      morbidity and mortality therefore it is important to identify patients with GC
      from non-severe cholecystitis. The aim of this study is to determine biochemical
      and radiological markers, which is associated with the development GC and the
      value of C-reactive protein (CRP) at different cut-offs in predicting GC.
      METHODS: This is an observational cohort study of all consecutive patients who
      presented with biliary symptoms to the emergency department in a large NHS
      Hospital in the UK, from January to December 2012. They had cholecystectomies
      performed either during index admission or electively at later date by a team of
      4 upper gastrointestinal surgeons. The gangrenous nature of the gallbladder was
      determined by operative findings and/or histopathology results. Parameters
      including age, gender, albumin, jaundice, gallbladder wall thickness on
      ultrasound scan, highest preoperative white blood count (WBC) and CRP value, were
      examined for their predictive value. RESULTS: 141 patients presented with acute
      biliary problems. 22 underwent emergency cholecystectomy and 119 were discharged
      and called back for elective surgery. Of these, 16 were gangrenous (11%).
      Patients with GC were significantly older (p = 0.016), had significantly higher
      CRP (p < 0.001) and WBC (p = 0.001), significantly lower albumin levels (p <
      0.001) and higher percentage with thick walled gallbladder (p < 0.001). We found
      that a CRP value of more than 200 mg/dL has a 50% positive predictive value and
      100% negative predictive value in predicting gangrenous cholecystitis with 100%
      sensitivity and 87.9% specificity. CONCLUSIONS: In this study CRP on its own has
      been shown to have high predictive value in predicting GC, but larger studies are
      needed to validate this finding. Monitoring trend of CRP in patients with acute
      cholecystitis may help early diagnosis and decision for early surgical
      intervention.

PMID- 24856180
TI  - Design, synthesis and evaluation of novel quinazoline-2,4-dione derivatives as
      chitin synthase inhibitors and antifungal agents.
AB  - A series of novel 1-methyl-3-substituted quinazoline-2,4-dione derivatives were
      designed, synthesized, and characterized by (1)H NMR, (13)C NMR and MS spectral
      data. Their inhibition against chitin synthase (CHS) and antifungal activities
      were evaluated in vitro. Results showed compounds 5b, 5c, 5e, 5f, 5j, 5k, 5l, and
      5o had strong inhibitory potency against CHS. Compound 5c, which has the highest
      potency among these compounds, had a half-inhibition concentration (IC50) of
      0.08mmol/L, while polyoxin B as positive drug had IC50 of 0.18mmol/L. These IC50
      values of compounds 5i, 5m, 5n, and 5s were greater than 0.75mmol/L, which
      revealed that those compounds had weak inhibition activity against CHS. Moreover,
      most of these compounds exhibited moderate to excellent antifungal activities. In
      detail, to Candida albicans, the activities of compound 5g and 5k were 8-fold
      stronger than that of fluconazole and 4-fold stronger than that of polyoxin B; to
      Aspergillus flavus, the activities of 5g, 5l and 5o were16-fold stronger than
      that of fluconazole and 8-fold stronger than that of polyoxin B; to Cryptococcus
      neoformans, the minimum-inhibition-concentration (MIC) values of compounds 5c,
      5d, 5e and 5l were comparable to those of fluconazole and polyoxin B. The
      antifungal activities of these compounds were positively correlated to their IC50
      values against CHS. Furthermore, these compounds had negligible actions to
      bacteria. Therefore, these compounds were promising selective antifungal agents. 

PMID- 24856181
TI  - SAR studies on hydropentalene derivatives--Important core units of biologically
      active tetramic acid macrolactams and ptychanolides.
AB  - Structurally diverse bicyclo[3.3.0]octanes were prepared and tested for their
      biological activity. Both the antiproliferative activity and the results of
      phenotypic characterization varied with the substitution patterns. Two
      derivatives displayed high inhibitory (IC50 <=3MUM) activity against the L-929
      cell line, but differed in their mode of action. A cluster analysis with
      impedance profiling data showed the two compounds in relationship to microtubule
      interfering compounds. In PtK2 cells treated with both derivatives a perturbing
      effect on the microtubular network was observed, whereas the actin cytoskeleton
      in incubated PtK2 cells was disturbed only by one compound. The effects on
      tubulin and actin polymerization could be confirmed by in vitro polymerization
      experiments.

PMID- 24856182
TI  - Combination of cyclohexane and piperazine based kappa-opioid receptor agonists:
      Synthesis and pharmacological evaluation of trans,trans-configured
      perhydroquinoxalines.
AB  - Desymmetrization of the pseudochiral (2r)-configured cyclohexane-1,2,3-triamines
      8 with dimethyl oxalate led to racemic aminoquinoxaline-2,3-diones 9. Selective
      introduction of the kappa pharmacophoric structural elements pyrrolidine and 3,4
      dichlorophenylacetamide with a two-carbon distance afforded conformationally
      restricted kappa agonists 13-15 based on the quinoxaline ring system. In
      competitive radioligand receptor binding studies the benzylamine 13b, the
      secondary amine 14b, and the carbamate 15 displayed high kappa receptor affinity.
      The Ki value of the lead compound derived methoxycarbonyl derivative 15 is 9.7nM.
      However, the kappa affinity of 15 is exceeded by 13b and 14b with a basic
      functional group instead of the methoxycarbonyl group in 1-position of the
      quinoxaline system. The chlorine atoms of the dichlorophenylacetyl residue are
      essential, since the corresponding phenylacetyl analogs show considerably reduced
      kappa affinity. The potent kappa ligands 13b, 14b and 15 are selective over the
      related MU- and delta-opioid receptors, sigma1, sigma2 and NMDA receptors. In the
      [(35)S]GTPgammaS-binding assay 13b behaved as partial agonist with lower activity
      than U-69,593. 

PMID- 24856183
TI  - Ultrapure ajulemic acid has improved CB2 selectivity with reduced CB1 activity.
AB  - Ajulemic acid, a side-chain analog of Delta(8)-THC-11-oic acid, was designed as a
      potent therapeutic agent free of the psychotropic adverse effects typical of most
      cannabinoids. Subsequent studies of ajulemic acid have yielded widely divergent
      findings on the occurrence of these adverse effects. To help resolve these
      discrepancies, we have prepared highly purified ajulemic acid using a different
      synthetic method than previously reported in the literature and compared its
      cannabinoid receptor binding constants with those obtained using several other
      preparations from different sources. Whereas CB2 binding did not vary greatly
      among all of the samples, the CB1 binding showed a wide range of affinities. The
      highly purified product (JBT-101) reported here had the weakest affinity for CB1
      while the original preparation (HU-239) showed the strongest affinity for CB1.
      The CB1/CB2 ratio of affinities was 12.3 for JBT-101 whereas that for HU-239 was
      0.19, a 65-fold difference. Functional responses such as catalepsy and
      hypothermia using JBT-101 versus HU-239 displayed reduced CB1 activity in keeping
      with the receptor binding data. Thus, earlier conclusions on the limited
      therapeutic index for ajulemic acid need to be reconsidered in the light of the
      data now obtained using JBT-101. 

PMID- 24856184
TI  - Oxidation of cyanobenzocycloheptatrienes: Synthesis, photooxygenation reaction
      and carbonic anhydrase isoenzymes inhibition properties of some new benzotropone
      derivatives.
AB  - The oxidation of some cyanocycloheptatrienes with CrO3 and pyridine was
      investigated and a few new nitrile functionalised benzotropone derivatives were
      obtained. Photooxygenation reaction of these products was also studied. The
      structures of the formed products were determined on the basis of NMR
      spectroscopy and the formation mechanism of unusual products was discussed. Human
      carbonic anhydrase isoenzymes I, and II (hCA I and hCA II) inhibition properties
      of nitrile functionalized new benzotropone derivatives were also studied. Both CA
      isozymes were inhibited in the low micromolar range by these nitrile
      functionalized benzotropone analogues. The newly synthesized benzotropone
      derivatives showed inhibition constants in the sub-micromolar range (2.51
      4.06MUM). The best hCA I inhibition was observed in 5H-benzocycloheptene-7
      carbonitrile (Ki: 2.88+/-0.86MUM). On the other hand, 5-oxo-5H
      benzocycloheptatriene-7-carbonitrile showed the powerful inhibitory effect
      against hCA II (Ki: 2.51+/-0.34MUM). 

PMID- 24856185
TI  - Inhibition by active site directed covalent modification of human glyoxalase I.
AB  - The glyoxalase pathway is responsible for conversion of cytotoxic methylglyoxal
      (MG) to d-lactate. MG toxicity arises from its ability to form advanced glycation
      end products (AGEs) on proteins, lipids and DNA. Studies have shown that
      inhibitors of glyoxalase I (GLO1), the first enzyme of this pathway, have
      chemotherapeutic effects both in vitro and in vivo, presumably by increasing
      intracellular MG concentrations leading to apoptosis and cell death. Here, we
      present the first molecular inhibitor, 4-bromoacetoxy-1-(S-glutathionyl)-acetoxy
      butane (4BAB), able to covalently bind to the free sulfhydryl group of Cys60 in
      the hydrophobic binding pocket adjacent to the enzyme active site and partially
      inactivate the enzyme. Our data suggests that partial inactivation of homodimeric
      GLO1 is due to the modification at only one of the enzymatic active sites.
      Although this molecule may have limited use pharmacologically, it may serve as an
      important template for the development of new GLO1 inhibitors that may combine
      this strategy with ones already reported for high affinity GLO1 inhibitors,
      potentially improving potency and specificity. 

PMID- 24856187
TI  - Characteristics and medical-care-seeking of head and neck cancer patients: a
      population-based cross-sectional survey.
AB  - OBJECTIVES: Well-known risk factors, such as smoking and alcohol consumption,
      easily denounce head and neck cancer patients as smokers, alcohol abusers, and
      persons who are socially excluded and have low socioeconomic status. To diagnose
      these patients as early as possible, we should not have a prejudiced assumption
      of their characteristics. MATERIALS AND METHODS: We collected detailed data on
      patient characteristics and health behavior and explored whether these traits had
      any effect on seeking medical advice in a population-based cross-sectional study
      involving 85 patients with head and neck cancer diagnosed between January 2003
      and December 2007, residing in two health care districts (population 1,600,000)
      in Finland. The data were gathered from patient charts and questionnaires. The
      questionnaire data were compared with the general population in Finland. RESULTS:
      We found these patients to be ordinary elderly people whose demographic and
      social features resembled those of the general population. They smoked more
      often, but otherwise had a rather healthy lifestyle. Only half were aware that
      smoking and alcohol consumption were risk factors of head and neck cancer. In a
      multivariate analysis, fear of physicians (adjusted odds ratio 11.0; 95%
      confidence interval 1.2-103), medical-care-seeking for symptoms other than pain
      (18.5; 2.2-156), and not suspecting cancer (11.2; 1.7-75.1) were independent risk
      factors for delayed consultation (combined appraisal and help-seeking interval
      over 3 months). CONCLUSION: Head and neck cancer patients deviated from the same
      aged general population only in excessive smoking. Fear of doctors, having no
      pain, and no suspicion of cancer resulted in delayed medical-care-seeking.

PMID- 24856188
TI  - Diagnostic and therapeutic implications of new molecular biomarkers in salivary
      gland cancers.
AB  - Salivary gland carcinomas (SGCs) are uncommon tumors, constituting approximately
      5% of all cancers of the head and neck. They are a heterogeneous group of
      diseases that pose significant diagnostic and therapeutic challenges. The
      treatment of patients with SGCs is mainly restricted to surgery and/or radiation
      therapy and there is only limited data available on the role of conventional
      systemic and targeted therapies in the management of patients with advanced
      disease. There is thus a great need to develop new molecular biomarkers to
      improve the diagnosis, prognostication, and therapeutic options for these
      patients. In this review, we will discuss the most recent developments in this
      field, with focus on pathognomonic gene fusions and other driver mutations of
      clinical significance. Comprehensive cytogenetic and molecular genetic analyses
      of SGCs have revealed a translocation-generated network of fusion oncogenes. The
      molecular targets of these fusions are transcription factors, transcriptional
      coactivators, and tyrosine kinase receptors. Prominent examples of clinically
      significant fusions are the MYB-NFIB fusion in adenoid cystic carcinoma and the
      CRTC1-MAML2 fusion in mucoepidermoid carcinoma. The fusions are key events in the
      molecular pathogenesis of these tumor types and contribute as new diagnostic,
      prognostic, and therapeutic biomarkers. Moreover, next-generation sequencing
      analysis of SGCs have revealed new druggable driver mutations, pinpointing
      alternative therapeutic options for subsets of patients. Continued molecular
      characterization of these fusions and their down-stream targets will ultimately
      lead to the identification of novel driver genes in SGCs and will form the basis
      for development of new therapeutic strategies for these patients. 

PMID- 24856189
TI  - Prospective dynamic balance control during the swing phase of walking: stability
      boundaries and time-to-contact analysis.
AB  - This study examined the prospective control of the swing phase in young healthy
      adults while walking at preferred speed over unobstructed ground and during
      obstacle clearance. Three aspects of swing were examined: (1) the relation of the
      body Center of Mass (CoM) to the stability boundaries at the base of support; (2)
      a dynamic time-to-contact analysis of the CoM and swing foot to these boundaries;
      and (3) the role of head movements in the prospective control of gait and field
      of view assessment. The time-to-contact analysis of CoM and swing foot showed
      less stable swing dynamics in the trail foot compared to the lead foot in the
      approach to the unstable equilibrium, with the CoM leading the swing foot and
      crossing the anterior stability boundary before the swing foot. Compensations in
      temporal coupling occurred in the trail limb during the late swing phase. Time-to
      contact analysis of head movement showed stronger prospective control of the lead
      foot, while fixation of the field of view occurred earlier in swing and was
      closer to the body in the obstacle condition compared to unobstructed walking.
      The dynamic time-to-contact analysis offers a new approach to assessing the
      unstable swing phase of walking in different populations. 

PMID- 24856190
TI  - Effect of light curing protocol on degree of conversion of composites.
AB  - OBJECTIVE: To evaluate the degree of conversion (DC) of two light-cured
      composites with different protocols of light curing. MATERIALS AND METHODS: One
      hundred and ninety two specimens (n = 8) were prepared (5 mm * 2 mm) according to
      experimental groups: two composite resins (Filtek Supreme and four seasons);
      three light curing protocols [20 s with the tip of the light curing unit (LCU)
      device touching composite surface (C); 20 s with the tip of the LCU at 8 mm
      distant from composite surface (D); and tip of the LCU at 8 mm distant from
      composite surface and polymerization time required to obtain a radiant exposure
      of 16 J/cm(2) (DS)]. Four LCUs (Bluephase 16i, Ultralume LED 5, XL 3000 and
      Optilux 501C) were used. DC of the bottom and top surface of specimens were
      measured using a FTIR spectrometer. Data were statistically analyzed by 3-way
      split splot ANOVA and Tukey's test (alpha = 0.05). RESULTS: The results showed
      that DC of the top surface was higher than the bottom at all experimental
      conditions (p < 0.0001). Overall, the curing at 8 mm of distance did not affect
      conversion rate on the top surface (p > 0.05), but bottom surfaces showed DC
      reduction (p < 0.05). The highest monomer conversion values were observed for C
      and DS situations. CONCLUSION: The distance between the LCU and material surface
      and radiant exposure can affect the DC. Polymerization at distance should be
      performed with curing units with higher light power and/or extended exposure
      time.

PMID- 24856191
TI  - The effect of recommending a CPP-ACPF product on salivary and plaque pH levels in
      orthodontic patients: a randomized cross-over clinical trial.
AB  - OBJECTIVE: Along with their re-mineralizing capacity, calcium phosphopeptide
      amorphous calcium phosphate products combined with fluoride (CPP-ACPF) could also
      be beneficial by neutralizing acidic salivary and plaque pH. The purpose was to
      evaluate the effect of CPP-ACPF on salivary and plaque pH in orthodontic
      patients. MATERIALS AND METHODS: As a triple-blind, cross-over randomized trial,
      30 orthodontic patients with fixed appliances (age range = 15.70 +/- 4.08 years)
      were recruited and randomly assigned to two groups. A CPP-ACPF paste (MI Paste
      Plus, GC America, Alsip, IL) was used by group 1 (n = 15) and a placebo by group
      2 (n = 15) for 1 month. After a 1 month washout period, patients used the
      alternative paste for another month. Plaque and salivary pH levels were measured
      at all before and after periods. RESULTS: By applying MI Paste Plus, the plaque
      pH increased from 5.81 +/- 0.45 to 6.60 +/- 0.38 (p < 0.05), whereas the before
      and after salivary pH recordings, which were 6.72 +/- 0.43 and 6.71 +/- 0.38,
      respectively, remained statistically unchanged (p > 0.05). CONCLUSION: MI Paste
      Plus can be clinically beneficial in increasing plaque pH levels, but has no
      effect on the salivary pH.

PMID- 24856193
TI  - Possible misidentification of Mycobacterium yongonense.

PMID- 24856195
TI  - Oral and injectable synthetic progestagens effectively manipulate the estrous
      cycle in the Przewalski's horse (Equus ferus przewalskii).
AB  - To date, there has been limited research on manipulation of the estrous cycle in
      endangered equids. The objectives of this study were to assess the efficacy of
      using combinations of: (a) oral altrenogest and PGF2alpha, and (b) injectable
      altrenogest and PGF2alpha for manipulation of ovarian activity in Przewalski's
      mares. Reproductive cycles were monitored by assessing follicular changes with
      rectal ultrasound and changes in urinary steroid hormones. In Study 1, five
      cycling mares were treated with oral altrenogest (n=11 cycles) for 14 days. In
      Study 2, cycling mares were treated with oral altrenogest for 12 days (n=5
      cycles; n=5 mares) or a single injection of biorelease altrenogest (n=10 cycles;
      n=6 mares). In all study groups, PGF2alpha was given 2 days before cessation of
      progestagen treatment. In Study 1, mares responded in six of 11 cycles (54%)
      where treatment occurred with normal ovarian follicular development post hormone
      therapy. In Study 2, mares responded in four of five (80%, oral altrenogest) and
      eight of 10 (80%, injectable altrenogest) cycles with the development of an
      ovulatory follicle. With the use of injectable altrenogest, there was an obvious
      suppression of urinary estrogens and progetsagens. These results indicate that
      manipulation of the estrous cycle of Przewalski's mares can be achieved by
      administering oral (12 days) or injectable form of altrenogest in conjunction
      with PGF2alpha. Findings in the present study may have long term application for
      the development of timed artificial insemination as a genetic management tool for
      this critically endangered equid.

PMID- 24856196
TI  - Case detection of disease by NHS Health Checks in Warwickshire, England and
      comparison with predicted performance.

PMID- 24856197
TI  - Appraisal of guidelines developed by the World Health Organization.
AB  - OBJECTIVE: To appraise the quality of guidelines developed by the World Health
      Organization (WHO) that were approved by its Guidelines Review Committee (GRC)
      and identify strengths and weaknesses in the guideline development process. STUDY
      DESIGN: Cross-sectional. METHODS: Three individuals independently assessed GRC
      approved WHO guidelines using the Appraisal of Guidelines for Research and
      Evaluation II instrument (AGREE II). Scores were standardized across domains and
      overall quality was determined through consensus. RESULTS: 124 guidelines met
      inclusion criteria and were assessed. 58 guidelines were recommended for use, 58
      were recommended with modifications and eight were not recommended. The highest
      scoring domains across guidelines were scope and purpose, and clarity of
      presentation. The recommended guidelines had higher rigor of development and
      applicability domain scores in comparison to other guidelines. 77% of the
      guidelines referenced an underlying evidence review and 49% used GRADE to assess
      the body of evidence or the strength of the recommendation. The domains in need
      of improvement included stakeholder engagement, editorial independence, and
      applicability. Guidelines not recommended for use were generally insufficient in
      their rigor of development. CONCLUSIONS: WHO guidelines need further improvement,
      most importantly in the rigor of their development (i.e., use of evidence
      reviews). Other areas for improvement include increased stakeholder engagement, a
      more explicit process for recommendation formulation and disclosure of interests,
      discussion of the facilitators, barriers, resource implications, and criteria for
      monitoring the outcomes of guideline implementation. WHO guidelines can improve
      through increased transparency, adherence to the WHO Handbook for Guideline
      Development, and better oversight by the GRC.

PMID- 24856198
TI  - British healthy-weights serviced for disabled children are largely based on
      inappropriate data.

PMID- 24856199
TI  - Outbreak of Salmonella infantis gastroenteritis among people who had eaten at a
      hash house in southern Italy.
AB  - OBJECTIVES: To describe an outbreak of acute gastroenteritis in people who had
      eaten at a hash house in southern Italy. STUDY DESIGN: Case-control study.
      METHODS: A clinical case of gastroenteritis was defined as a person who had eaten
      at the hash house from 29 August to 4 September 2011 and who experienced defined
      gastrointestinal symptoms within 72 hours, or a person with a laboratory
      confirmed salmonella infection without symptoms. A convenience sample was
      enrolled as the control group. Environmental and human samples were collected,
      and Salmonella infantis was identified by polymerase chain reaction. Univariate
      analysis was performed for each food type, and multivariate analysis was
      performed for each food type and demographic variable (gender, age). RESULTS:
      Twenty-three cases of gastroenteritis were notified between 1 and 4 September
      2011, two of which were admitted to the local hospital. Multivariate analysis
      showed that porchetta [odds ratio (OR) 22.0, 95% confidence interval (CI) 3.2
      152.6, z = 3.13, P = 0.002] and roasted meat (OR 14.4, 95% CI 1.7-122.0, z =
      2.45, P = 0.014) were associated with gastrointestinal symptoms. Environmental
      and human isolates exhibited the same sequence type (ST 32). CONCLUSIONS: This
      experience highlighted that, in the control of a foodborne outbreak, integrated
      epidemiological and laboratory surveillance enables rapid identification of the
      source of infection, thus reducing the risk of an epidemic.

PMID- 24856200
TI  - Why do people exercise? A cross-sectional study of motives to exercise among
      Danish adults.

PMID- 24856201
TI  - Two weeks in Geneva.

PMID- 24856202
TI  - Initial effects of a free swimming pilot programme on the physical activity
      levels of young people.

PMID- 24856203
TI  - Diastereoselective synthesis of 2-phenyl-3-(trifluoromethyl)piperazines as
      building blocks for drug discovery.
AB  - The synthesis of enantiomerically pure cis- and trans-2-phenyl-3
      (trifluoromethyl)piperazines is described. It involved, as the key step, a
      diastereoselective nucleophilic addition of the Ruppert-Prakash reagent (TMSCF3)
      to alpha-amino sulfinylimines bearing Ellman's auxiliary. This methodology allows
      an entry into hitherto unknown trifluoromethylated and stereochemically defined
      piperazines, key scaffold components in medicinal chemistry. 

PMID- 24856205
TI  - A systematic review of the impact of oral contraceptives on cognition.
AB  - Combined oral contraceptives (OCs) are the most commonly prescribed medication in
      women of reproductive age, but despite widespread use, their effect on cognitive
      performance remains controversial. Given strong evidence for the neurological
      impact of reproductive hormones, a clear rationale for investigation exists. This
      systematic review sought to identify, collate and critically appraise studies
      assessing the impact of OCs on cognition in healthy premenopausal women. Ovid
      MEDLINE, PsychINFO and EMBASE were comprehensively searched using relevant
      keywords for original peer-reviewed observational studies or randomised trials
      published after 1960. Of 1289 references screened, 22 studies were eligible for
      inclusion. Assembled evidence supports a cognitive impact of OCs restricted to
      specific domains; however, the quality of evidence is poor. The most consistent
      finding is improved verbal memory with OC use. Evidence is also emerging that
      differing progestin androgenicity may lead diverse OC formulations to
      differentially impact certain cognitive domains, such as visuospatial ability. At
      present, evidence is inconclusive, contradictory and limited by methodological
      inconsistencies. There is scope for further research in this area to definitively
      determine the cognitive impact of OCs. 

PMID- 24856206
TI  - Binocular integration in the mouse lateral geniculate nuclei.
AB  - A key task for the visual system is to combine spatially overlapping
      representations of the environment, viewed by either eye, into a coherent image.
      In cats and primates, this is accomplished in the cortex [1], with retinal
      outputs maintained as separate monocular maps en route through the lateral
      geniculate nucleus (LGN). While this arrangement is also believed to apply to
      rodents [2, 3], this has not been functionally confirmed. Accordingly, here we
      used multielectrode recordings to survey eye-specific visual responses across the
      mouse LGN. Surprisingly, while we find that regions of space visible to both eyes
      do indeed form part of a monocular representation of the contralateral visual
      field, we find no evidence for a corresponding ipsilateral representation.
      Instead, we find many cells that can be driven via either eye. These inputs
      combine to enhance the detection of weak stimuli, forming a binocular
      representation of frontal visual space. This extensive thalamic integration marks
      a fundamental distinction in mechanisms of binocular processing between mice and
      other mammals.

PMID- 24856207
TI  - The right dorsal habenula limits attraction to an odor in zebrafish.
AB  - BACKGROUND: The habenula consists of an evolutionarily conserved set of nuclei
      that control neuromodulator release. In lower vertebrates, the dorsal habenula
      receives innervation from sensory regions, but the significance of this is
      unclear. Here, we address the role of the habenula in olfaction by imaging neural
      activity in larval zebrafish expressing GCaMP3 throughout the habenula and by
      carrying out behavioral assays. RESULTS: Activity in several hundred neurons
      throughout the habenula was recorded using wide-field fluorescence microscopy,
      fast focusing, and deconvolution. This enabled the creation of 4D maps of odor
      evoked activity. Odors activated the habenula in two broad spatiotemporal
      patterns. Increasing concentrations of a putative social cue (a bile salt) evoked
      a corresponding increase in neuronal activity in the right dorsal habenula. In
      behavioral assays, fish were attracted to intermediate concentration of this cue
      but avoided higher concentration. Increasing cholinergic activity through
      nicotine exposure rendered the intermediate concentration aversive in a habenula
      dependent manner. Pharmacologically blocking nicotinic receptors or lesioning the
      right dorsal habenula attenuated avoidance. CONCLUSIONS: These data provide
      physiological and functional evidence that the habenula functions as a higher
      center in zebrafish olfaction and suggest that activity in the right dorsal
      subdomain gates innate attraction to specific odors.

PMID- 24856208
TI  - Decoding sound and imagery content in early visual cortex.
AB  - Human early visual cortex was traditionally thought to process simple visual
      features such as orientation, contrast, and spatial frequency via feedforward
      input from the lateral geniculate nucleus (e.g., [1]). However, the role of
      nonretinal influence on early visual cortex is so far insufficiently investigated
      despite much evidence that feedback connections greatly outnumber feedforward
      connections [2-5]. Here, we explored in five fMRI experiments how information
      originating from audition and imagery affects the brain activity patterns in
      early visual cortex in the absence of any feedforward visual stimulation. We show
      that category-specific information from both complex natural sounds and imagery
      can be read out from early visual cortex activity in blindfolded participants.
      The coding of nonretinal information in the activity patterns of early visual
      cortex is common across actual auditory perception and imagery and may be
      mediated by higher-level multisensory areas. Furthermore, this coding is robust
      to mild manipulations of attention and working memory but affected by orthogonal,
      cognitively demanding visuospatial processing. Crucially, the information fed
      down to early visual cortex is category specific and generalizes to sound
      exemplars of the same category, providing evidence for abstract information
      feedback rather than precise pictorial feedback. Our results suggest that early
      visual cortex receives nonretinal input from other brain areas when it is
      generated by auditory perception and/or imagery, and this input carries common
      abstract information. Our findings are compatible with feedback of predictive
      information to the earliest visual input level (e.g., [6]), in line with
      predictive coding models [7-10].

PMID- 24856209
TI  - Insulin-FOXO3 signaling modulates circadian rhythms via regulation of clock
      transcription.
AB  - Circadian rhythms are responsive to external and internal cues, light and
      metabolism being among the most important. In mammals, the light signal is sensed
      by the retina and transmitted to the suprachiasmatic nucleus (SCN) master clock
      [1], where it is integrated into the molecular oscillator via regulation of clock
      gene transcription. The SCN synchronizes peripheral oscillators, an effect that
      can be overruled by incoming metabolic signals [2]. As a consequence, peripheral
      oscillators can be uncoupled from the master clock when light and metabolic
      signals are not in phase. The signaling pathways responsible for coupling
      metabolic cues to the molecular clock are being rapidly uncovered [3-5]. Here we
      show that insulin-phosphatidylinositol 3-kinase (PI3K)-Forkhead box class O3
      (FOXO3) signaling is required for circadian rhythmicity in the liver via
      regulation of Clock. Knockdown of FoxO3 dampens circadian amplitude, an effect
      that is rescued by overexpression of Clock. Subsequently, we show binding of
      FOXO3 to two Daf-binding elements (DBEs) located in the Clock promoter area,
      implicating Clock as a transcriptional target of FOXO3. Transcriptional
      oscillation of both core clock and output genes in the liver of FOXO3-deficient
      mice is affected, indicating a disrupted hepatic circadian rhythmicity. Finally,
      we show that insulin, a major regulator of FOXO activity [6-9], regulates Clock
      levels in a PI3K- and FOXO3-dependent manner. Our data point to a key role of the
      insulin-FOXO3-Clock signaling pathway in the modulation of circadian rhythms.

PMID- 24856211
TI  - Maintenance of a genetic polymorphism with disruptive natural selection in
      stickleback.
AB  - The role of natural selection in the maintenance of genetic variation in wild
      populations remains a major problem in evolution. The influence of disruptive
      natural selection on genetic variation is especially interesting because it might
      lead to the evolution of assortative mating or dominance [1, 2]. In theory,
      variation can persist at a gene under disruptive natural selection, but the
      process is little studied and there are few examples [3, 4]. We report a stable
      polymorphism in the bony armor of threespine stickleback maintained with a
      deficit of heterozygotes at the major underlying gene, Ectodysplasin (Eda) [5].
      The deficit vanishes at the embryo life stage only to re-emerge in adults,
      indicating that disruptive natural selection, rather than nonrandom mating, is
      the cause. The mechanism enabling long-term persistence of the polymorphism is
      unknown, but disruptive selection is predicted to be frequency dependent,
      favoring homozygous genotypes when they become rare. Further research on the
      ecological and evolutionary processes affecting individual genes will ultimately
      lead to a better understanding of the causes of genetic variation in populations.

PMID- 24856210
TI  - Maternal origins of developmental reproducibility.
AB  - Cell fate decisions during multicellular development are precisely coordinated,
      leading to highly reproducible macroscopic structural outcomes [1-3]. The origins
      of this reproducibility are found at the molecular level during the earliest
      stages of development when patterns of morphogen molecules emerge reproducibly
      [4, 5]. However, although the initial conditions for these early stages are
      determined by the female during oogenesis, it is unknown whether reproducibility
      is perpetuated from oogenesis or reacquired by the zygote. To address this issue
      in the early Drosophila embryo, we sought to count individual maternally
      deposited bicoid mRNA molecules and compare variability between embryos with
      previously observed fluctuations in the Bicoid protein gradient [6, 7]. Here, we
      develop independent methods to quantify total amounts of mRNA in individual
      embryos and show that mRNA counts are highly reproducible between embryos to
      within ~9%, matching the reproducibility of the protein gradient. Reproducibility
      emerges from perfectly linear feedforward processes: changing the genetic dosage
      in the female leads to proportional changes in both mRNA and protein numbers in
      the embryo. Our results indicate that the reproducibility of the morphological
      structures of embryos originates during oogenesis, which is when the expression
      of maternally provided patterning factors is precisely controlled.

PMID- 24856212
TI  - Misbinding of color and motion in human visual cortex.
AB  - A fundamental challenge for the visual system is to integrate visual features
      into a coherent scene, known as the binding problem. The neural mechanisms of
      feature binding are hard to identify because of difficulties in separating active
      feature binding from feature co-occurrence. In previous studies on feature
      binding, visual features were superimposed and presented simultaneously. Neurons
      throughout the visual cortex are known to code multiple features. Therefore, the
      observed binding effects could be due to the physical co-occurrence of features
      and the sensory representation of feature pairings. It is uncertain whether the
      mechanisms responsible for perceptual binding were actually recruited. To address
      this issue, we performed psychophysical and fMRI experiments to investigate the
      neural mechanisms of a steady-state misbinding of color and motion, because
      feature misbinding is probably the most striking evidence for the active
      existence of the binding mechanisms. We found that adapting to the color-motion
      misbinding generated the color-contingent motion aftereffect, as well as the
      color-contingent motion adaptation effect in visual cortex. Notably, V2 exhibited
      the strongest adaptation effect, which significantly correlated with the
      aftereffect across subjects. Furthermore, effective connectivity analysis using
      dynamic causal modeling showed that the misbinding was closely associated with
      enhanced feedback from V4 and V5 to V2. These findings provide strong evidence
      for active feature binding in early visual cortex and suggest a critical role of
      reentrant connections from specialized intermediate areas to early visual cortex
      in this process.

PMID- 24856213
TI  - Dancing bees communicate a foraging preference for rural lands in high-level agri
      environment schemes.
AB  - Since 1994, more than ?41 billion has been spent in the European Union on agri
      environment schemes (AESs), which aim to mitigate the effects of anthropomorphic
      landscape changes via financial incentives for land managers to encourage
      environmentally friendly practices [1-6]. Surprisingly, given the substantial
      price tag and mandatory EU member participation [2], there is either a lack of
      [1] or mixed [1, 2, 7] evidence-based support for the schemes. One novel source
      of data to evaluate AESs may be provided by an organism that itself may benefit
      from them. Honeybees (Apis mellifera), important pollinators for crops and
      wildflowers [8, 9], are declining in parts of the world from many factors,
      including loss of available forage from agricultural intensification [10-13]. We
      analyzed landscape-level honeybee foraging ecology patterns over two years by
      decoding 5,484 waggle dances from bees located in the center of a mixed, urban
      rural 94 km(2) area, including lands under government-funded AESs. The waggle
      dance, a unique behavior performed by successful foragers, communicates to
      nestmates the most profitable foraging locations [14-16]. After correcting for
      distance, dances demonstrate that honeybees possess a significant preference for
      rural land managed under UK Higher Level AESs and a significant preference
      against rural land under UK Organic Entry Level AESs. Additionally, the two most
      visited areas contained a National and Local Nature Reserve, respectively. Our
      study demonstrates that honeybees, with their great foraging range and sensitive
      response to forage quality, can be used as bioindicators to monitor large areas
      and provide information relevant to better environmental management.

PMID- 24856214
TI  - The neural basis of somatosensory remapping develops in human infancy.
AB  - When we sense a touch, our brains take account of our current limb position to
      determine the location of that touch in external space [1, 2]. Here we show that
      changes in the way the brain processes somatosensory information in the first
      year of life underlie the origins of this ability [3]. In three experiments we
      recorded somatosensory evoked potentials (SEPs) from 6.5-, 8-, and 10-month-old
      infants while presenting vibrotactile stimuli to their hands across uncrossed-
      and crossed-hands postures. At all ages we observed SEPs over central regions
      contralateral to the stimulated hand. Somatosensory processing was influenced by
      arm posture from 8 months onward. At 8 months, posture influenced mid-latency SEP
      components, but by 10 months effects were observed at early components associated
      with feed-forward stages of somatosensory processing. Furthermore, sight of the
      hands was a necessary pre-requisite for somatosensory remapping at 10 months.
      Thus, the cortical networks [4] underlying the ability to dynamically update the
      location of a perceived touch across limb movements become functional during the
      first year of life. Up until at least 6.5 months of age, it seems that human
      infants' perceptions of tactile stimuli in the external environment are heavily
      dependent upon limb position.

PMID- 24856216
TI  - Wrestling with the hymen: knowledge and attitudes.
AB  - BACKGROUND: There is a cultural gap between girls with virginity problems and the
      western healthcare professionals (HCPs) they approach for help. METHOD: The lack
      of knowledge concerning virginity-related issues among non-Western migrants in
      the Netherlands is illustrated by means of a selection of quotations from
      messages received by a single sexual health service. The differences in cultural
      beliefs between non-Western and Western societies are also overviewed.
      CONCLUSION: HCPs should have a better grasp of the ins and outs of the virginity
      norms prevailing in migrant communities. This would enable them to counsel the
      young women concerned more efficiently and to find practical, culturally
      acceptable solutions to their dilemmas.

PMID- 24856217
TI  - Study of outpatient neurological care in the Region of Madrid: The impact of
      implementing free choice of hospital.
AB  - INTRODUCTION: A new model permitting free choice of hospital has been introduced
      in the Region of Madrid. This may result in changes in how outpatient
      neurological care is provided and managed. The purpose of this study is to
      analyse initial visits to a general neurology department in the Region of Madrid
      and record the health district corresponding to each patient's residence.
      METHODS: Observational and prospective study of a cohort of patients making
      initial outpatient visits to a neurology department between 16 September 2013 and
      16 January 2014. RESULTS: The study included 1109 patients (63.8% women, mean age
      55.2+/-20.5). The most frequent diagnostic groups were periodic headache,
      cognitive disorders, and neuromuscular diseases. Non-neurological diseases were
      diagnosed in 1.1% of the cases. The mean time of delay was 7.2+/-5.1 days.
      Residents within the hospital's health district made up 73.8% of the total, while
      26.2% chose a hospital outside of the health district corresponding to their
      residences. In the latter group, 59.5% made the choice based on the level of care
      offered, while 39.7% changed hospitals due to shorter times to consultation. The
      patients who came from another health district were younger (50.7 vs 57.3,
      P<.0001) and had a lower rate of discharges on the first visit (16.4% vs 30.1%,
      P<.0001). CONCLUSION: The model of free choice of hospital delivers significant
      changes in healthcare management and organisation. Reasons given for choosing
      another hospital are more ample experience and shorter delays with respect to the
      home district hospital. Management of patients from outside the health district
      is associated with greater complexity.

PMID- 24856218
TI  - A novel ER stress-independent function of the UPR in angiogenesis.
AB  - Tumors rely on the unfolded protein response (UPR) and angiogenesis to survive
      the metabolic stress of hypoxia. Karali et al. (2014) revealed that VEGF
      signaling engages UPR sensors in an unconventional manner that is independent of
      endoplasmic reticulum (ER) stress, mediated by mTOR signaling to promote
      endothelial cell survival and angiogenesis. 

PMID- 24856219
TI  - Ubiquitin puts actin in its place.
AB  - In this issue of Molecular Cell, Yuan et al. (2014) report that the Cul3-KLHL20
      E3 ubiquitin ligase regulates protein anterograde transport from the trans-Golgi
      network (TGN) by facilitating localized actin assembly at the TGN through K33
      linked ubiquitination of coronin 7. 

PMID- 24856220
TI  - Principles and properties of eukaryotic mRNPs.
AB  - The proper processing, export, localization, translation, and degradation of
      mRNAs are necessary for regulation of gene expression. These processes are
      controlled by mRNA-specific regulatory proteins, noncoding RNAs, and core
      machineries common to most mRNAs. These factors bind the mRNA in large complexes
      known as messenger ribonucleoprotein particles (mRNPs). Herein, we review the
      components of mRNPs, how they assemble and rearrange, and how mRNP composition
      differentially affects mRNA biogenesis, function, and degradation. We also
      describe how properties of the mRNP "interactome" lead to emergent principles
      affecting the control of gene expression. 

PMID- 24856222
TI  - Types of social support and their relationships to physical and depressive
      symptoms and health-related quality of life in patients with heart failure.
AB  - OBJECTIVES: To examine the various types of social support associated with
      physical and depressive symptoms and health-related quality of life (HRQOL) in
      patients with heart failure (HF) and the mediating effects of symptoms on the
      relationship between social support and HRQOL. BACKGROUND: Patients with HF have
      a high burden of physical and depressive symptoms, along with poor HRQOL. Social
      support may improve symptoms and HRQOL. METHODS: Data on social support (marital
      status, family relationships, relationships with health care providers, social
      networks, emotional support, and instrumental support), symptoms, and HRQOL were
      collected from 71 patients. Hierarchical regression was used to analyze the data.
      RESULTS: Emotional support was related to all physical and depressive symptoms
      and HRQOL. Physical and depressive symptoms mediated the relationship between
      emotional support and HRQOL. CONCLUSIONS: Further studies are needed to identify
      ways to improve emotional support and determine whether the improvement leads to
      improvements in symptoms and HRQOL.

PMID- 24856221
TI  - The histone deacetylases sir2 and rpd3 act on ribosomal DNA to control the
      replication program in budding yeast.
AB  - In S. cerevisiae, replication timing is controlled by epigenetic mechanisms
      restricting the accessibility of origins to limiting initiation factors. About
      30% of these origins are located within repetitive DNA sequences such as the
      ribosomal DNA (rDNA) array, but their regulation is poorly understood. Here, we
      have investigated how histone deacetylases (HDACs) control the replication
      program in budding yeast. This analysis revealed that two HDACs, Rpd3 and Sir2,
      control replication timing in an opposite manner. Whereas Rpd3 delays initiation
      at late origins, Sir2 is required for the timely activation of early origins.
      Moreover, Sir2 represses initiation at rDNA origins, whereas Rpd3 counteracts
      this effect. Remarkably, deletion of SIR2 restored normal replication in
      rpd3Delta cells by reactivating rDNA origins. Together, these data indicate that
      HDACs control the replication timing program in budding yeast by modulating the
      ability of repeated origins to compete with single-copy origins for limiting
      initiation factors. 

PMID- 24856223
TI  - Right pulmonary artery agenesis with patent ductus arteriosus and Eisenmenger
      syndrome: a rare case diagnosed during the postpartum period.
AB  - Unilateral absence of a pulmonary artery a very rare congenital disorder. We here
      present a case of a 22-year-old female patient with agenesis of the right
      pulmonary artery accompanying patent ductus arteriosus and Eisenmenger syndrome,
      diagnosed by chest X-ray and multidetector computed tomography 5 days after
      giving birth. 

PMID- 24856225
TI  - The lower limit of normal in the evaluation of pulmonary function.

PMID- 24856215
TI  - A SUF Fe-S cluster biogenesis system in the mitochondrion-related organelles of
      the anaerobic protist Pygsuia.
AB  - BACKGROUND: Many microbial eukaryotes have evolved anaerobic alternatives to
      mitochondria known as mitochondrion-related organelles (MROs). Yet, only a few of
      these have been experimentally investigated. Here we report an RNA-seq-based
      reconstruction of the MRO proteome of Pygsuia biforma, an anaerobic
      representative of an unexplored deep-branching eukaryotic lineage. RESULTS:
      Pygsuia's MRO has a completely novel suite of functions, defying existing
      "function-based" organelle classifications. Most notable is the replacement of
      the mitochondrial iron-sulfur cluster machinery by an archaeal sulfur
      mobilization (SUF) system acquired via lateral gene transfer (LGT). Using
      immunolocalization in Pygsuia and heterologous expression in yeast, we show that
      the SUF system does indeed localize to the MRO. The Pygsuia MRO also possesses a
      unique assemblage of features, including: cardiolipin, phosphonolipid, amino
      acid, and fatty acid metabolism; a partial Kreb's cycle; a reduced respiratory
      chain; and a laterally acquired rhodoquinone (RQ) biosynthesis enzyme. The latter
      observation suggests that RQ is an electron carrier of a fumarate reductase-type
      complex II in this MRO. CONCLUSIONS: The unique functional profile of this MRO
      underscores the tremendous plasticity of mitochondrial function within eukaryotes
      and showcases the role of LGT in forging metabolic mosaics of ancestral and newly
      acquired organellar pathways.

PMID- 24856224
TI  - Increased levels of plasma CXC-Chemokine Ligand 10, 12 and 16 are associated with
      right ventricular function in patients with idiopathic pulmonary arterial
      hypertension.
AB  - OBJECTIVE: To investigate plasma levels of CXC-Chemokine Ligand 10 (CXCL10), CXC
      Chemokine Ligand 12 (CXCL12) and CXC-Chemokine Ligand 16 (CXCL16) in patients
      with idiopathic pulmonary arterial hypertension (IPAH). METHODS: Plasma levels of
      biomarkers were measured by enzyme-linked immunosorbent assay in 61 patients with
      IPAH and 20 healthy volunteers. RESULTS: Plasma CXCL10, CXCL12 and CXCL16
      concentrations were increased significantly in IPAH patients compared with
      controls, and significantly correlated with N-terminal pro-brain natriuretic
      peptide, tricuspid annulus plane systolic excursion and right ventricular
      ejection fraction. CONCLUSIONS: Increased levels of CXCL10, CXCL12 and CXCL16 are
      associated with right ventricular dysfunction in patients with IPAH.

PMID- 24856226
TI  - A rare case of silent transmural myocardial infarction with diffuse ST elevations
      complicated by concomitant severe hyperkalemia.
AB  - It is well described that certain group of patients do not display the typical
      symptoms of myocardial infarction (MI). Elderly patients, diabetics and those
      with previous coronary artery bypass graft surgery are at high risk for silent
      MI. The diagnosis of Acute MI in the emergency room (ER) is mainly based on the
      electrocardiogram (EKG) findings of ST elevations or new onset left bundle branch
      block which is supported by the clinical presentation and positive biomarkers
      when present. The diagnoses can sometimes become challenging when the patient is
      asymptomatic and has coincidental finding of hyperkalemia with diffuse ST segment
      elevations simulating that seen with electrolyte disturbance. Despite the well
      known pseudoinfarction pattern of hyperkalemia, acute MI should be ruled out
      first. A high index of suspicion is needed, especially in high risk patients. We
      think that in rare clinical situation when the diagnosis is in doubt, MI should
      be ruled out, as time has a high impact on patient mortality. An urgent bedside
      echocardiogram is very beneficial in excluding regional wall motion abnormalities
      and preventing any delay in destination therapy for transmural MI. We present a
      67 years old female with history of diabetes and chronic kidney disease sent by
      her nephrologist to the ER for severe hyperkalemia (Potassium 7.2
      milliequivalent/L). She was found to have ST elevations on EKG despite having no
      chest pain or distress. On cardiac catheterization she had a total occlusion of
      the proximal left circumflex artery, with a filling defect consistent with large
      thrombus. 

PMID- 24856227
TI  - Symptom burden in stable COPD patients with moderate or severe airflow
      limitation.
AB  - OBJECTIVES: To describe a multidimensional symptom profile in patients with
      stable chronic obstructive pulmonary disease (COPD) and determine whether symptom
      experience differed between patients with moderate or severe airflow limitations.
      BACKGROUND: Patients with severe airflow limitation experience numerous symptoms,
      but little is known regarding patients with moderate airflow limitation. METHODS:
      A multidimensional symptom profile (Memorial Symptom Assessment Scale) was
      assessed in 42 outpatients with moderate and 49 with severe airflow limitations.
      RESULTS: The mean number of symptoms in the total sample was 7.9 (+/-4.3) with no
      difference between patients with moderate and severe airflow limitations. The
      most prevalent symptoms with the highest MSAS symptom burden scores were
      shortness of breath, dry mouth, cough, sleep problems, and lack of energy in both
      groups. CONCLUSIONS: Patients with moderate or severe airflow limitations
      experience multiple symptoms with high severity and distress. An assessment of
      their multidimensional symptom profile might contribute to better symptom
      management.

PMID- 24856228
TI  - Steroid use in kidney transplant recipients presented with acute myocardial
      infarction.
AB  - Suppression of the hypothalamic-pituitary-adrenal axis due to chronic exogenous
      steroid use is the most common cause of secondary adrenal insufficiency. Most
      kidney transplant recipients receive steroid therapy for immunosuppression; they
      are also at high risk for acute coronary events which can increase their
      physiological stress. Use of steroids early in the course of acute myocardial
      infarction (MI) raises concerns about the possibility of an increased risk of
      aneurysm formation and myocardial rupture. We present six case reports of kidney
      transplant recipients. Two of these recipients developed adrenal insufficiency
      after acute anterior MI; the life-threatening situation was successfully managed
      with corticosteroid administration. Four of these kidney transplant recipients
      presented with acute anterior MI; in these patients prophylactic steroid therapy
      prevented adrenal insufficiency, without any complication of the MI. We recommend
      the use of prophylactic corticosteroids for kidney transplant recipients to
      prevent adrenal insufficiency in the early course of acute MI. 

PMID- 24856229
TI  - In COPD patients on prolonged mechanical ventilation heart rate variability
      during the T-piece trial is better after pressure support plus PEEP: a pilot
      physiological study.
AB  - OBJECTIVES: To evaluate heart rate variability (HRV), hemodynamics, mechanics,
      dyspnea and blood gases following different mechanical ventilation (MV) settings.
      BACKGROUND: No study has evaluated physiological changes during T-piece trials
      following different MV settings. METHODS: In 8 COPD patients on prolonged MV we
      applied in random order two MV settings: i) pressure support (PS) 20 cm H2O +
      positive end-expiratory pressure (PEEP) 0 cm H2O (setting-1) and ii) PS 15 cm H2O
      + PEEP 5 cm H2O (setting-2), each followed by a 30 min T-piece trial. RESULTS:
      Setting-1 induced greater minute ventilation, tidal volume/inspiratory time and
      lower pulmonary artery occlusion pressure; setting-2 reduced intrinsic PEEP.
      Mechanics and hemodynamics data did not differ, but all HRV time domain indices
      were reduced only after setting-1, suggesting a decreased parasympathetic and
      increased sympathetic cardiac modulation. CONCLUSIONS: The T-piece trial
      following setting-2 seems less stressful on neural control of HRV. Future studies
      on T-piece trials should consider the residual effect of the MV setting.

PMID- 24856230
TI  - "Releasing a lot of poisons from my mind": patients' delusional memories of
      intensive care.
AB  - OBJECTIVES: To describe intensive care unit (ICU) patients' delusional memories
      and interpretations of those memories. BACKGROUND: Delusional memories of the ICU
      are distressing for patients and may impact psychological recovery. METHODS: This
      is a secondary analysis from a study of mechanically ventilated patients' recall
      in relation to sedation. Subjects, recruited from one medical-surgical ICU,
      participated in structured interviews after extubation. RESULTS: Subjects (n =
      35) with a mean age of 66 (SD 12.9) and on the ventilator a median of 4.5 days
      provided detailed descriptions of delusional memories of being shackled, caged,
      strangled, or being in a foreign country. Delusions were very real and
      frightening in the moment. Subjects had difficulty connecting to reality to allow
      processing of the delusions. CONCLUSIONS: Patients' delusional memories of ICU
      share common distressing themes. Assisting patients' to connect to real ICU
      events and process delusional memories may help with psychological recovery after
      critical illness.

PMID- 24856232
TI  - Medication adherence and its associated factors among Chinese community-dwelling
      older adults with hypertension.
AB  - OBJECTIVE: To investigate the factors that influence medication adherence in
      Chinese community-dwelling older adults with hypertension. METHODS: A cross
      sectional study was conducted with a convenience sample of 382 older adults with
      hypertension recruited from six health centers in Macao, China. Chinese versions
      of the Morisky 4-Item Self-Report Measure of Medication-Taking Behavior, Fear of
      Intimacy with Helping Professionals scale and Exercise of Self-care Agency scale
      were administered to participants. RESULTS: Participants older than 65 years
      (beta = .118, p = .017), with a low level of education (beta = .128, p = .01),
      who had more than one other common disease (beta = .120, p = .015), were on long
      term medication (beta = .221, p < .001) and who reported higher self-care (beta =
      .188, p = .001), had better medication adherence. CONCLUSIONS: Health care
      professionals should consider these factors when planning medication regimens for
      Chinese older adults with hypertension, to enhance medication adherence and
      improve patient outcomes.

PMID- 24856231
TI  - Economical aspect of PET/CT-guided diagnosis of suspected infective endocarditis
      in a patient with implantable cardioverter-defibrillator.
AB  - We present a case report of potential reduction of hospitalization costs due to
      utilization of PET/CT in a diagnostic work-up of a patient with an implantable
      cardioverter-defibrillator and suspicion of infective endocarditis. The PET/CT
      scan would have shorten hospital stay, prevented clinical complications and
      reduced the cost of hospitalization by 45%. 

PMID- 24856233
TI  - Use of inhaled nitric oxide in preterm infants: a regional survey of practices.
AB  - OBJECTIVES: To conduct a regional survey of neonatal intensive care unit (NICU)
      Directors in Australia and New Zealand (ANZ) to ascertain current practice.
      BACKGROUND: Use of inhaled nitric oxide (iNO) therapy in infants < 34 weeks
      gestational age is not supported by current evidence. METHODS: A cross-sectional
      electronic survey based on structured questionnaire was conducted amongst the
      Directors of all the tertiary neonatal intensive care units in Australia and New
      Zealand Neonatal Network (ANZNN). Information was collected on indications,
      dosage, monitoring response and weaning for iNO therapy. RESULTS: The survey was
      sent to 28 units, of which 2 were quaternary units' not routinely admitting
      preterm infants, hence were excluded from analysis. The response rate was 77%
      (20/26). Majority of units (16; 80%) did not have preterm specific protocol. In
      almost all units nitric was used as early rescue for hypoxemic respiratory
      failure (95%; 19/20). Neonatologist performed functional echocardiography (fECHO)
      was frequently used for prior assessment (90%) and monitoring (65%). Variations
      were noted regarding initiating criteria, dosage and weaning strategies.
      CONCLUSIONS: Wide variation in practice was noted highlighting the need for the
      formulation of consensus guidelines.

PMID- 24856235
TI  - Understanding public responses to chemical, biological, radiological and nuclear
      incidents--driving factors, emerging themes and research gaps.
AB  - This paper discusses the management of public responses to incidents involving
      chemical, biological, radiological and nuclear materials (CBRN). Given the
      extraordinary technical and operational challenges of a response to a CBRN
      release including, but not limited to, hazard detection and identification,
      casualty decontamination and multi-agency co-ordination, it is not surprising
      that public psychological and behavioural responses to such incidents have
      received limited attention by scholars and practitioners alike. As a result, a
      lack of understanding about the role of the public in effective emergency
      response constitutes a major gap in research and practice. This limitation must
      be addressed as a CBRN release has the potential to have wide-reaching
      psychological and behavioural impacts which, in turn, impact upon public
      morbidity and mortality rates. This paper addresses a number of key issues: why
      public responses matter; how responses have been conceptualised by practitioners;
      what factors have been identified as influencing public responses to a CBRN
      release and similar extreme events, and what further analysis is needed in order
      to generate a better understanding of public responses to inform the management
      of public responses to a CBRN release. 

PMID- 24856236
TI  - Jewish provisions for protecting children: modern rabbis advocate non-violence.

PMID- 24856234
TI  - [Sentinel node biopsy after neoadjuvant chemotherapy in breast cancer. Its
      relation with molecular subtypes].
AB  - OBJECTIVE: To evaluate the influence of the molecular subtype (MS) in the
      Sentinel Node Biopsy (SNB) technique after neoadjuvant chemotherapy (NAC) in
      women with locally advanced breast cancer (BC) and a complete axillary response
      (CR). MATERIAL AND METHODS: A prospective study involving 70 patients with BC
      treated with NAC was carried out. An axillary lymph node dissection was performed
      in the first 48 patients (validation group: VG), and in case of micro- or
      macrometastases in the therapeutic application phase (therapy group:TG).
      Classified according to MS: 14 luminal A; 16 luminal B HER2-, 13 luminal B HER2+,
      10HER2+ non-luminal, 17 triple-negative. RESULTS: SNB was carried out in 98.6% of
      the cases, with only one false negative result in the VG (FN=2%). Molecular
      subtype did not affect SN detection. Despite the existence of axillary CR,
      statistically significant differences were found in the proportion of
      macrometastasis (16.7% vs. 35.7%, p=0.043) on comparing the pre-NAC cN0 and cN+.
      Breast tumor response to NAC varied among the different MS, this being lowest in
      luminal A (21.5%) and highest in non-luminal HER2+ group (80%). HER2+ and triple
      negative were the groups with the best axillary histological response both when
      there was prior clinical involvement and when there was not. CONCLUSIONS:
      Molecular subtype is a predictive factor of the degree of tumor response to NAC
      in breast cancer. However, it does not affect SNB detection and efficiency. SNB
      can also be used safely in women with prior node involvement as long as a
      complete clinical and radiological assessment is made of the node response to
      NAC.

PMID- 24856237
TI  - The nurture and protection of children in Islam: perspectives from Islamic
      sources: Islamic texts command affection, care, and education.

PMID- 24856241
TI  - MR arthrography of the shoulder: optimizing pulse sequence protocols for the
      evaluation of cartilage and labrum.
AB  - OBJECTIVES: To compare axial T1weighted fat-saturated (T1w fs) and T1w non-fs
      sequences, and coronal T1w-fs and T2w-fs sequences, for evaluation of cartilage
      and labrum using CT arthrography (CTA) as the reference. METHODS: Patients had MR
      arthrography (MRA) and CTA of the shoulder on the same day. Cartilage was
      assessed for superficial and full thickness focal and diffuse damage. Labral
      lesions were graded for Bankart variants and SLAP lesions. CTA images were read
      for the same features. The diagnostic performance of MRA including area under the
      curve (AUC) was evaluated against CTA. RESULTS: When comparing axial sequences,
      the diagnostic performance for cartilage lesion detection on T1w non-fs was 61.9%
      (sensitivity) 93.6% (specificity) and 89.5% (accuracy) with AUC 0.782, while that
      for T1w fs was 61.9%, 94.0%, 89.8% and 0.783. For labral assessment, it was
      89.1%, 93.0%, 91.4% and 0.919 for T1w non-fs, and 89.9%, 94.0%, 92.6% and 0.922
      for T1w fs. Comparing coronal sequences, diagnostic performance for cartilage was
      42.5%, 97.5%, 89.8% and 0.702 for T1w fs, and 38.4%, 98.7%, 90.2%, and 0.686 for
      T2w fs. For the labrum it was 85.1%, 87.5%, 86.2%, and 0.868 for T1w fs, and
      75.7%, 97.5%, 80.8% and 0.816 for T2w fs. CONCLUSIONS: Axial T1w fs and T1w non
      fs sequences are comparable in their ability to diagnose cartilage and labral
      lesions. Coronal T1w fs sequence offers slightly higher sensitivity but slightly
      lower specificity than T2w fs sequence for diagnosis of cartilage and labral
      lesions.

PMID- 24856245
TI  - Proteome profile of a pandemic Vibrio parahaemolyticus SC192 strain in the
      planktonic and biofilm condition.
AB  - Vibrio parahaemolyticus is one of the leading causative agents of foodborne
      diseases in humans. In this study, the proteome profiles of the pandemic strain
      V. parahaemolyticus SC192 belonging to the O3:K6 serovar during the planktonic
      and biofilm stages were analyzed by two-dimensional liquid chromatography coupled
      to tandem mass spectrometry. This non-gel-based multidimensional protein
      identification technology approach identified 45.5% of the proteome in the
      reference genome V. parahaemolyticus RIMD 2210633. This is the largest proteome
      coverage obtained so far in V. parahaemolyticus and provides evidence for
      expression of 27% of the hypothetical proteins. Comparison of the planktonic and
      biofilm proteomes based on their cluster of orthologous groups, gene ontologies
      and KEGG pathways provides basic information on biofilm specific functions and
      pathways. To the authors' knowledge, this is the first study to generate a global
      proteome profile of the pandemic strain of V. parahaemolyticus and the method
      reported here could be used to rapidly obtain a snapshot of the proteome of any
      microorganism at a given condition. 

PMID- 24856242
TI  - Metabolic syndrome and endothelin-1 mediated vasoconstrictor tone in
      overweight/obese adults.
AB  - OBJECTIVE: To determine whether endothelin (ET)-1 vasoconstrictor tone is greater
      in overweight and obese adults with the metabolic syndrome (MetS).
      MATERIALS/METHODS: Forty overweight/obese middle-aged and older adults (age: 43
      71 years; BMI: 25.1-36.9 kg/m2) were studied: 20 without MetS (13 M/7 F) and 20
      with MetS (13 M/7 F). MetS was established according to NCEP ATP III guidelines.
      Forearm blood flow (FBF; plethysmography) responses to intra-arterial infusion of
      selective ET(A) receptor blockade (BQ-123; 100 nmol/min; for 60 min) and non
      selective ET(A/B) receptor blockade (BQ-123 + BQ-788 [50 nmol/min for 60 min])
      were determined. RESULTS: In response to the selective ET(A) antagonism, there
      was a significant increase in forearm blood flow from baseline in both groups.
      However, the increase in forearm blood flow was significantly higher (P=0.03;
      ~45%) in the overweight/obese group with MetS than the group without MetS. In
      contrast, there were no significant group differences in FBF responses to non
      selective ET(A/B) receptor blockade. Peak vasodilator responses to nonselective
      ET(A/B) blockade were ~50% higher than baseline blood flow in the
      overweight/obese groups without and with MetS. CONCLUSION: MetS is associated
      with higher ET-1 vasoconstrictor tone in overweight/obese adults. The enhanced ET
      1 vasoconstrictor activity with MetS is mediated by the ET(A) receptor subtype.

PMID- 24856243
TI  - Differences in virulence repertoire and cell invasive potential of group A
      Streptococcus emm1-2 in comparison to emm1 genotype.
AB  - Group A streptococcus (GAS, Streptococcus pyogenes) type emm1 is widely
      associated with streptococcal invasive disease. This type is prevalent worldwide
      but is rare in India. Instead, emm1-2 type which is closely related to emm1 but
      is a distinct type is more prevalent. Although emm1 has been well characterized,
      information available on emm1-2 is rare. In this study we present a comparative
      study of both types. DNA microarray analysis showed segregation of emm1 and emm1
      2 isolates into two distinct clusters. Out of 229 arrayed genes, 83-87% were
      present, 6-9% absent and 4-8% genes were ambiguous in emm1 isolates. emm1-2
      strains harboured only 68-77%, 11-13% were absent and 10-20% ambiguous genes.
      Fourteen genes, present in all emm1, were completely absent in the emm1-2
      isolates. sfb1 is a gene which encodes for Streptococcal fibronectin binding
      adhesin and invasin which has restricted distribution among different emm types
      of GAS. A variant of sfb1 (sfb1-2) was the only gene which was present in all
      emm1-2 isolates, but absent from all emm1 strains. Sfb1 and Sfb1-2 differ in
      sequences in the aromatic domain and the proline rich repeat region, whereas the
      fibronectin binding region was conserved and exhibited similar fibronectin
      binding activity. The presence of Sfb1-2 in emm1-2 strains was concomitant with
      significantly higher fibronectin-binding and invasion efficiency of HEp-2 cells
      when compared to emm1 isolates. The role of Sfb1-2 in invasion was confirmed by
      latex bead assay. emm1-2 isolates follow membrane ruffling mechanism during
      invasion and intracellularly follow classical endocytic pathway. Further studies
      are required to understand the correlation between the presence of emm1-2
      isolates and the disease pattern in North India.

PMID- 24856246
TI  - Incorporating conditional random fields and active learning to improve sentiment
      identification.
AB  - Many machine learning, statistical, and computational linguistic methods have
      been developed to identify sentiment of sentences in documents, yielding
      promising results. However, most of state-of-the-art methods focus on individual
      sentences and ignore the impact of context on the meaning of a sentence. In this
      paper, we propose a method based on conditional random fields to incorporate
      sentence structure and context information in addition to syntactic information
      for improving sentiment identification. We also investigate how human interaction
      affects the accuracy of sentiment labeling using limited training data. We
      propose and evaluate two different active learning strategies for labeling
      sentiment data. Our experiments with the proposed approach demonstrate a 5%-15%
      improvement in accuracy on Amazon customer reviews compared to existing
      supervised learning and rule-based methods. 

PMID- 24856247
TI  - Immediate return preference emerged from a synaptic learning rule for return
      maximization.
AB  - Animals including human often prefer immediate returns to larger delayed returns.
      It holds true in the human communications. Standard interpretation of the
      immediate return preference is that an animal might subjectively discount the
      value of a delayed reward, and that might choose the larger valued one. The
      interpretation has been successfully applied to explain behavior of many species
      including human. However, the description is not necessarily sufficient to apply
      for interactions of individuals. This study adopts a different approach to seek a
      possibility that immediate return preference may be reproduced by learning rule
      to maximize objective outcomes. We show that a synaptic learning rule to achieve
      the temporal difference (TD) learning for outcome maximization fails the
      maximization and exhibits immediate return preference if the context is not
      properly represented as a internal state. 

PMID- 24856239
TI  - Tyrosyl-DNA-phosphodiesterases (TDP1 and TDP2).
AB  - TDP1 and TDP2 were discovered and named based on the fact they process 3'- and 5'
      DNA ends by excising irreversible protein tyrosyl-DNA complexes involving
      topoisomerases I and II, respectively. Yet, both enzymes have an extended
      spectrum of activities. TDP1 not only excises trapped topoisomerases I (Top1 in
      the nucleus and Top1mt in mitochondria), but also repairs oxidative damage
      induced 3'-phosphoglycolates and alkylation damage-induced DNA breaks, and
      excises chain terminating anticancer and antiviral nucleosides in the nucleus and
      mitochondria. The repair function of TDP2 is devoted to the excision of
      topoisomerase II- and potentially topoisomerases III-DNA adducts. TDP2 is also
      essential for the life cycle of picornaviruses (important human and bovine
      pathogens) as it unlinks VPg proteins from the 5'-end of the viral RNA genome.
      Moreover, TDP2 has been involved in signal transduction (under the former names
      of TTRAP or EAPII). The DNA repair partners of TDP1 include PARP1, XRCC1, ligase
      III and PNKP from the base excision repair (BER) pathway. By contrast, TDP2
      repair functions are coordinated with Ku and ligase IV in the non-homologous end
      joining pathway (NHEJ). This article summarizes and compares the biochemistry,
      functions, and post-translational regulation of TDP1 and TDP2, as well as the
      relevance of TDP1 and TDP2 as determinants of response to anticancer agents. We
      discuss the rationale for developing TDP inhibitors for combinations with
      topoisomerase inhibitors (topotecan, irinotecan, doxorubicin, etoposide,
      mitoxantrone) and DNA damaging agents (temozolomide, bleomycin, cytarabine, and
      ionizing radiation), and as novel antiviral agents. 

PMID- 24856248
TI  - Discrete particle swarm optimization for identifying community structures in
      signed social networks.
AB  - Modern science of networks has facilitated us with enormous convenience to the
      understanding of complex systems. Community structure is believed to be one of
      the notable features of complex networks representing real complicated systems.
      Very often, uncovering community structures in networks can be regarded as an
      optimization problem, thus, many evolutionary algorithms based approaches have
      been put forward. Particle swarm optimization (PSO) is an artificial intelligent
      algorithm originated from social behavior such as birds flocking and fish
      schooling. PSO has been proved to be an effective optimization technique.
      However, PSO was originally designed for continuous optimization which confounds
      its applications to discrete contexts. In this paper, a novel discrete PSO
      algorithm is suggested for identifying community structures in signed networks.
      In the suggested method, particles' status has been redesigned in discrete form
      so as to make PSO proper for discrete scenarios, and particles' updating rules
      have been reformulated by making use of the topology of the signed network.
      Extensive experiments compared with three state-of-the-art approaches on both
      synthetic and real-world signed networks demonstrate that the proposed method is
      effective and promising. 

PMID- 24856249
TI  - Non-invasive quantification of lower limb mechanical alignment in flexion.
AB  - OBJECTIVE: Non-invasive navigation techniques have recently been developed to
      determine mechanical femorotibial alignment (MFTA) in extension. The primary aim
      of this study was to evaluate the precision and accuracy of an image-free
      navigation system with new software designed to provide multiple kinematic
      measurements of the knee. The secondary aim was to test two types of strap
      material used to attach optical trackers to the lower limb. METHODS: Seventy-two
      registrations were carried out on 6 intact embalmed cadaveric specimens (mean
      age: 77.8 +/- 12 years). A validated fabric strap, bone screws and novel rubber
      strap were used to secure the passive tracker baseplate for four full experiments
      with each knee. The MFTA angle was measured under the conditions of no applied
      stress, valgus stress, and varus stress. These measurements were carried out at
      full extension and at 30 degrees , 40 degrees , 50 degrees  and 60 degrees  of
      flexion. Intraclass correlation coefficients, repeatability coefficients, and
      limits of agreement (LOA) were used to convey precision and agreement in
      measuring MFTA with respect to each of the independent variables, i.e., degree of
      flexion, applied coronal stress, and method of tracker fixation. Based on the
      current literature, a repeatability coefficient and LOA of <= 3 degrees  were
      deemed acceptable. RESULTS: The mean fixed flexion for the 6 specimens was 12.8
      degrees  (range: 6-20 degrees ). The mean repeatability coefficient measuring
      MFTA in extension with screws or fabric strapping of the baseplate was <= 2
      degrees , compared to 2.3 degrees  using rubber strapping. When flexing the knee,
      MFTA measurements taken using screws or fabric straps remained precise
      (repeatability coefficient <= 3 degrees ) throughout the tested range of flexion
      (12.8-60 degrees ); however, using rubber straps, the repeatability coefficient
      was >3 degrees  beyond 50 degrees  flexion. In general, applying a varus/valgus
      stress while measuring MFTA decreased precision beyond 40 degrees  flexion. Using
      fabric strapping, excellent repeatability (coefficient <= 2 degrees ) was
      observed until 40 degrees  flexion; however, beyond 50 degrees  flexion, the
      repeatability coefficient was >3 degrees . As was the case with precision,
      agreement between the invasive and non-invasive systems was satisfactory in
      extension and worsened with flexion. Mean limits of agreement between the
      invasive and non-invasive system using fabric strapping to assess MFTA were 3
      degrees  (range: 2.3-3.8 degrees ) with no stress applied and 3.9 degrees 
      (range: 2.8-5.2 degrees ) with varus and valgus stress. Using rubber strapping,
      the corresponding values were 4.4 degrees  (range: 2.8-8.5 degrees ) with no
      stress applied, 5.5 degrees  (range: 3.3-9.0 degrees ) with varus stress, and 5.6
      degrees  (range: 3.3-11.9 degrees ) with valgus stress. DISCUSSION: Acceptable
      precision and accuracy may be possible when measuring knee kinematics in early
      flexion using a non-invasive system; however, we do not believe passive trackers
      should be mounted with rubber strapping such as was used in this study. Flexing
      the knee appears to decrease the precision and accuracy of the system. The
      functions of this new software using image-free navigation technology have many
      potential clinical applications, including assessment of bony and soft tissue
      deformity, pre-operative planning, and post-operative evaluation, as well as in
      further pure research comparing kinematics of the normal and pathological knee.

PMID- 24856251
TI  - Reply to: "preoperative symptoms and inguinal herniorrhaphy".

PMID- 24856250
TI  - Dual-functionalized nanostructured biointerfaces by click chemistry.
AB  - The presentation of biologically active molecules at interfaces has made it
      possible to investigate the responses of cells to individual molecules in their
      matrix at a given density and spacing. However, more sophisticated methods are
      needed to create model surfaces that present more than one molecule in a
      controlled manner in order to mimic at least partially the complexity given in
      natural environments. Herein, we present dual-functionalized surfaces combining
      quasi-hexagonally arranged gold nanoparticles with defined spacings and a newly
      developed PEG-alkyne coating to functionalize the glass in the intermediate
      space. The PEG-alkyne coating provides an inert background for cell interactions
      but can be modified orthogonally to the gold nanoparticles with numerous azides,
      including spectroscopically active molecules, peptides, and biotin at controlled
      densities by the copper(I)-catalyzed azide alkyne click reaction. The
      simultaneous presentation of cRGD on the gold nanoparticles with 100 nm spacing
      and synergy peptide PHSRN in the space between has a striking effect on REF cell
      adhesion; cells adhere, spread, and form mature focal adhesions on the dual
      functionalized surfaces, whereas cells cannot adhere on either monofunctional
      surface. Combining these orthogonal functionalization methods creates a new
      platform to study precisely the crosstalk and synergy between different signaling
      molecules and clustering effects in ligand-receptor interactions. 

PMID- 24856252
TI  - Dengue virus type 3, South Pacific Islands, 2013.
AB  - After an 18-year absence, dengue virus serotype 3 reemerged in the South Pacific
      Islands in 2013. Outbreaks in western (Solomon Islands) and eastern (French
      Polynesia) regions were caused by different genotypes. This finding suggested
      that immunity against dengue virus serotype, rather than virus genotype, was the
      principal determinant of reemergence. 

PMID- 24856254
TI  - Size- and dose-dependent toxicity of cellulose nanocrystals (CNC) on human
      fibroblasts and colon adenocarcinoma.
AB  - A controlled preparation of cellulose nanocrystals of different sizes and shapes
      has been carried out by acid hydrolysis of microcrystalline cellulose. The size-
      and concentration-dependent toxicity effects of the resulting cellulose
      nanocrystals were evaluated against two different cell lines, NIH3T3 murine
      embryo fibroblasts and HCT116 colon adenocarcinoma. It could serve as a
      therapeutic platform for cancer treatment. 

PMID- 24856255
TI  - Distribution of semduramicin in hen eggs and tissues after administration of
      cross-contaminated feed.
AB  - Semduramicin is an ionophore coccidiostat used in the poultry industry as a feed
      additive. Cross-contamination of feeds for non-target animals with semduramicin
      is unavoidable. However, it is not known whether undesirable residues of
      semduramicin may occur in food after cross-contaminated feed is administered to
      animals. The aim of the work was to determine the levels of semduramicin in hen
      eggs (yolks and albumen) and tissues (liver, muscle, spleen, gizzard, ovarian
      yolks and ovaries) after administration of feed contaminated with 0.27 mg kg(-1)
      of this coccidiostat. The residues were determined using LC-MS/MS. The
      distribution pattern confirmed the high lipophilicity of semduramicin. Residues
      were found mainly in egg yolks (28.8 ug kg(-1)), ovarian yolks (19.5 ug kg(-1))
      and liver (2.57 ug kg(-1)), while hens' muscle was free from semduramicin (LOD =
      0.1 ug kg(-1)). Among edible tissues, the maximum level (2 ug kg(-1)) was
      exceeded only in the liver. 

PMID- 24856256
TI  - Evaluation of fast 2D NMR for metabolomics.
AB  - Two-dimensional nuclear magnetic resonance (2D NMR) is increasingly explored as a
      tool for metabolomics because of its superior resolution compared to one
      dimensional NMR (1D NMR). However, 2D NMR is characterized by longer acquisition
      times, which makes it less suitable for high-throughput studies. In this Article,
      we evaluated two methods for the acceleration of nD NMR, ultrafast (UF) and
      nonuniform sampling (NUS), in the context of metabolomics. To this end, model
      samples mimicking the metabolic profile variations in serum from subjects
      affected by colorectal cancer and controls were analyzed by 1D (1)H NMR along
      with conventional and accelerated DQF-COSY and HSQC. A statistical analysis (OPLS
      DA) yielded similar results for the group separation with all techniques, but
      biomarker identification from 2D spectra was substantially enhanced, both in
      terms of number of molecules and easiness of assignment. Most interestingly, fast
      2D NMR techniques lead to similar results as conventional 2D NMR, opening the way
      for high-throughput metabolomics studies using 2D NMR. 

PMID- 24856257
TI  - Emergent properties of dense DNA phases toward artificial biosystems on a
      surface.
AB  - CONSPECTUS: The expression of genes in a cell in response to external signals or
      internal programs occurs within an environment that is compartmentalized and
      dense. Reconstituting gene expression in man-made systems is relevant for the
      basic understanding of gene regulation, as well as for the development of
      applications in bio- and nanotechnology. DNA polymer brushes assembled on a
      surface emulate a dense cellular environment. In a regime of significant chain
      overlap, the highly charged nature of DNA, its entropic degrees of freedom, and
      its interaction with transcription/translation machinery lead to emergent
      collective biophysical and biochemical properties, which are summarized in this
      Account. First, we describe a single-step photolithographic biochip on which
      biomolecules can be immobilized. Then, we present the assembly of localized DNA
      brushes, a few kilo-base pairs long, with spatially varying density, reaching a
      DNA concentration of ~10(7) base pairs/MUm(3), which is comparable to the value
      in E. coli. We then summarize the response of brush height to changes in density
      and mono- and divalent ionic strength. The balance between entropic elasticity
      and swelling forces leads to a rich phase behavior. At no added salt, polymers
      are completely stretched due to the osmotic pressure of ions, and at high salt
      they assume a relaxed coil conformation. Midrange, the brush height scales with
      ratio of density and ionic strength to the third power, in agreement with the
      general theory of polyelectrolyte brushes. In response to trivalent cations, DNA
      brushes collapse into macroscopic dendritic condensates with hysteresis,
      coexistence, and a hierarchy of condensation with brush density. We next present
      an investigation of RNA transcription in the DNA brush. In general, the brush
      density entropically excludes macromolecules, depleting RNA polymerase
      concentration in the brush compared to the bulk, therefore reducing transcription
      rate. The orientation of transcription promoters with respect to the surface also
      affects the rate with a lower value for outward compared to inward transcription,
      likely due to local changes of RNA polymerase concentrations. We hypothesize that
      equalizing the macromolecular osmotic pressure between bulk and brush with the
      addition of inert macromolecules would overcome the entropic exclusion of DNA
      associated proteins, and lead to enhanced biochemical activity. Finally, we
      present protein synthesis cascades in DNA brushes patterned at close proximity,
      as a step toward biochemical signaling between brushes. Examining the synthesis
      of proteins polymerizing into crystalline tubes suggests that on-chip molecular
      traps serve as nucleation sites for protein assembly, thereby opening
      possibilities for reconstituting nanoscale protein assembly pathways.

PMID- 24856258
TI  - Synthesis of the TACO scaffold as a new selectively deprotectable
      conformationally restricted triazacyclophane based scaffold.
AB  - The synthesis of a new triazacyclophane scaffold (TACO scaffold) containing three
      selectively deprotectable amines is described. The TACO scaffold is
      conformationally more constrained than our frequently used TAC scaffold, due to
      introduction of a substituent on the para position of the benzoic acid hinge,
      which prevents ring flipping and makes it more attractive than the TAC scaffold
      for preparation of artificial receptor molecules or for mimicking discontinuous
      epitopes toward protein mimics when more preorganization is required. 

PMID- 24856259
TI  - Sixth INTERMACS annual report: a 10,000-patient database.
AB  - The sixth annual report of the Interagency Registry for Mechanically Assisted
      Circulatory Support (INTERMACS) summarizes the first 8 years of patient
      enrollment. The analysis is based on data from >10,000 patients and updates
      demographics, survival, adverse events and risk factors. Among patients with
      continuous-flow pumps, actuarial survival continues to be 80% at 1 year and 70%
      at 2 years. The report features a comparison of two eras of continuous-flow
      durable devices in the USA in terms of device strategy, patient profiles, adverse
      event burden, survival and quality of life. 

PMID- 24856263
TI  - FT-IR and FT-Raman spectra of 6-chlorouracil: molecular structure, tautomerism
      and solid state simulation. A comparison between 5-chlorouracil and 6
      chlorouracil.
AB  - A Raman and IR study of the biomolecule 6-chlorouracil was carried out in the
      solid state. The unit cell found in the crystal was simulated as a tetramer form
      by density functional calculations. Specific scale factors and scaling equations
      deduced from uracil molecule were employed in the predicted wavenumbers of 6
      chlorouracil. The scaled wavenumbers were used in the reassignment of the IR and
      Raman experimental bands. Good reproduction of the experimental wavenumbers is
      obtained and the % error is very small in the majority of cases. A comparison
      between the molecular structure and charge distribution of 6-chlorouracil and 5
      chlorouracil molecules was presented. The effect of the hydration with the PCM
      model in the molecular structure and charges was discussed. The optimum tautomers
      of 6-chlorouracil were optimized and analyzed. Six of them were related to those
      of uracil molecule. The effect of the halogen substitution in the sixth position
      of the pyrimidine ring in the stability of the different tautomers was evaluated.
      HOMO and LUMO orbital energy analysis were carried out. 

PMID- 24856264
TI  - Oxidative stress and lipid peroxidation in prolonged users of methamphetamine.
AB  - BACKGROUND AND AIMS: Methamphetamine abuse results in numerous adverse health
      effects. Formation of free radicals may be a contributing factor. Methamphetamine
      has produced free radicals in animal studies. Present study was conducted to
      evaluate status of oxidative stress and lipid peroxidation among chronic
      methamphetamine users. METHODS: Ninety six individuals were selected randomly
      from methamphetamine abusers who had referred to rehabilitation and treatment
      center for drug abuse and their closed relatives, after providing informed
      consent. Blood samples were taken from each of the studied individuals. Ferric
      reducing ability of plasma (FRAP) assay and serum level of MDA (malondialdehyde)
      were used to assess the total anti-oxidant power and status of lipid peroxidation
      of the body, respectively. The results were analyzed by SPSS software version
      16.0. Differences among groups were determined by T-test. FINDINGS: Total anti
      oxidant powers of plasma were 0.31+/-0.04 micromoles/liter and 0.46+/-0.05
      micromoles/liter in methamphetamine abusers and control groups respectively. The
      difference was statistically significant (p-value=0.04). Levels of MDA were
      4.38+/-5.05 micromoles/liter and 1.72+/-2.04 micromoles/liter in methamphetamine
      abusers and control group. The difference was statistically significant (p
      value=0.01). CONCLUSION: results of present study suggest that prolonged use of
      methamphetamine exerts oxidative stress on the body and enhances lipid
      peroxidation. The event may contribute to emergence of adverse effects of acute
      and prolonged use of methamphetamine; such as loss of attention, psychomotor
      dysfunction, and cognitive deficits. It is recommended that antioxidants were
      included in drug regimens prescribed for methamphetamine abusers who referred to
      physicians to seek medical care for any reason.

PMID- 24856265
TI  - The effect of pomelo mix ethyl acetate extract on CYP3A6 and P-glycoprotein gene
      transcripts in rabbits.
AB  - Pomelo fruit juice and pomelo ethylacetate extract have been shown to increase
      the bioavailability of some CYP3A substrates. The purpose of this study was to
      investigate if this effect might be contributed to by changes in CYP3A and p
      glycoprotein mRNAs levels in the liver and proximal small intestine. The ethyl
      acetate extract of pomelo mix was administered for 7 days to 10 rabbits. Nine
      rabbits were administered tap water for 7 days. The administration was through
      oral intubation to the stomach. On the 8(th) day, the rabbits were sacrificed,
      and the liver and the proximal 15 cm of the small intestine were dissected. Total
      RNA was extracted from the specimens and cDNA was prepared by quantitative real
      time-polymerase chain reaction (RT-PCR) using specific primers. The ethyl acetate
      extract of pomelo mix reduced the mRNA expression of CYP3A6 almost 5-folds in the
      intestine and 2-folds in the liver. In contrast, a 1-fold increase to the p
      glycoprotein mRNA expression was observed under the same experimental conditions.
      In conclusion, the ethyl acetate extract of pomelo mix reduced the mRNA
      expression of CYP3A6 in both intestine and liver but to different degrees, while
      the p-glycoprotein mRNA expression was not reduced. 

PMID- 24856266
TI  - "Wear the world like a loose garment...a request for help from psychiatric
      nurses".

PMID- 24856267
TI  - Burnout in psychiatric nursing: examining the interplay of autonomy, leadership
      style, and depressive symptoms.
AB  - It is important to consider ways in which nurses can be protected from
      experiencing the effects of burnout. This study examined the relationships
      between leadership style of psychiatric nurse supervisors, work role autonomy,
      and psychological distress in relation to psychiatric nurse burnout. Eighty-nine
      psychiatric nurses from Montana and New York hospitals completed an online survey
      that assessed their work-related experiences. Overall, results of this study
      indicate that the participants were experiencing high levels of emotional
      exhaustion and depersonalization when compared to a normative sample of mental
      health workers. Results also showed that leadership style and work role autonomy
      are likely to be environmental factors that protect against burnout in nurses.
      Finally, it was shown that the relationship between depressive symptoms and the
      burnout component of personal accomplishment may be influenced by nurses'
      perceptions of the leadership style in their work environment. These findings are
      important because nurse supervisor leadership styles and amount of autonomy are
      characteristics of the work environment that may be amenable to change through
      training and intervention.

PMID- 24856268
TI  - "Our depression is different": Experiences and perceptions of depression in young
      Black men with a history of incarceration.
AB  - One in three Black men in the US faces difficulties obtaining employment, housing
      and maintaining self-sufficiency post incarceration. Felony records result in
      considerable social and economic vulnerability, placing many young Black men at
      risk for depression. Little is known about depression in Black men with felony
      records. Twenty Black men with a history of incarceration were interviewed to
      explore perceptions and experiences of depression. Emergent themes were anger and
      negativity, depression is weakness, invisible depression, being strong and going
      on, and our depression is different. Findings have implications for clinicians
      who initiate ongoing therapeutic relationships with young Black men.

PMID- 24856269
TI  - State of the science: group therapy interventions for sexually abused children.
AB  - Research investigating the use of group therapy treatment for sexually abused
      children is limited. This paper aims to review the current state of the science
      of group therapy and its outcomes with children and adolescents under age 18 who
      have experienced sexual abuse. A literature review was conducted which located
      eight articles meeting the inclusion criteria of this paper. These outcome
      studies utilized a wide array of theoretical orientations and intervention
      delivery, as well as an assortment of outcomes measurement. While the studies
      lacked consistency, there is some support that group therapy formats to treat
      sexually abused children and adolescents may be effective across a range of
      symptoms. Implications for practice, policy, and future research are discussed.

PMID- 24856272
TI  - Depression, anxiety and quality of life in caregivers of long-term home care
      patients.
AB  - Family caregivers of patient in long-term care facilities often have high rates
      of stress, burden and psychological illness. A descriptive study was carried out
      with 63 caregivers. Caregivers were asked to complete a demographic
      questionnaire, Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI) and
      Short form 36 (SF-36), which measures health related quality of life (QoL). The
      majority of caregivers were female (79.4%), and most often the daughter of the
      patient in long-term care (47.6%). The mean BDI score of the sample was 18.8, and
      the mean BAI score was 20.0. Almost all the mean scores referring to the QoL were
      decreased (lower than 50), with the exception of mental health. On the SF-36
      questionnaire, the lowest scores were observed on the role-emotional, role
      physical, social functioning and vitality scales of the SF-36.

PMID- 24856271
TI  - Gender differences in factors associated with delirium severity in older adults
      with dementia.
AB  - The purpose of this descriptive correlational study was to explore potential
      gender differences in the relationship of dementia severity, age, APOE status,
      cognitive reserve and co-morbidity (two potentially modifiable factors), to
      delirium severity in older adults. Baseline data from an ongoing clinical trial
      and a Poisson regression procedure were used in the analyses. Participants were
      148 elderly individuals with dementia and delirium admitted to post-acute care.
      In women, delirium severity was related to dementia severity (p=0.002) and co
      morbidity moderated that effect (p=0.03). In men, education was marginally
      associated with delirium severity (p=0.06). Implications for research are
      discussed.

PMID- 24856270
TI  - Memory and cancer: a review of the literature.
AB  - The mental health of cancer survivors has not always been the primary emphasis of
      treatment protocols since physical health outcomes have taken precedence. Older
      cancer survivors experience a double jeopardy since they are at risk for memory
      impairments and mild cognitive impairment and because they are greater than 55
      years of age. Of the 9.6 million cancer survivors in the US who have completed
      active treatment, many report cognitive difficulties, with labels such as "chemo
      brain," "not as sharp," "woolly-headedness," or the "mind does not work as
      quickly". To date, most of our knowledge of cognitive impairment in cancer
      survivors comes from female breast cancer survivors. Studies indicate that these
      survivors have diminished executive function, verbal memory, and motor function.
      Cancer survivors want to live independently in the community for as long as
      possible however, these cognitive deficits may prevent this desired lifestyle. To
      broaden our understanding this paper reviews the literature on the cognitive
      impairment and memory deficits experienced by three groups of cancer survivors
      breast, colorectal, and prostate cancer, that make up 60% of all survivors
      nationally. Even though mental health declined after a cancer diagnosis, the long
      term outcomes of cancer survivors did not differ from persons without cancer in
      depression or cognitive function. 

PMID- 24856273
TI  - A pilot study of iPad-assisted cognitive training for schizophrenia.
AB  - In this pilot study, we aimed to examine whether iPad-assisted cognitive training
      could be beneficial in ameliorating some of the cognitive impairment that
      accompany schizophrenia. Totally, 20 first-episode schizophrenia patients were
      randomly assigned to an experiment group (with cognitive training) or to a
      control group (without cognitive training). The N-back task was assessed at
      baseline and after intervention, to see what effects iPad-assisted training might
      have (week 4). The experimental group exhibited significant improvement in the
      accuracy rate at 2-back, and reaction time at 0, 1 and 2-back tasks. These
      findings suggest that iPad- or other technically-assisted cognitive training may
      potentially be a valid strategy for pursuing cognitive rehabilitation among those
      with schizophrenia.

PMID- 24856274
TI  - OSA symptoms associated with and predictive of anxiety in middle-aged men:
      secondary analysis of NHANES data.
AB  - OBJECT: This population-based study examined obstructive sleep apnea (OSA)
      symptoms predictive of anxiety in middle-aged men. METHOD: Secondary analyses
      were conducted on the National Health and Nutrition Examination Survey (NHANES)
      2007-2008 data using weighted samples and complex sample analysis techniques
      (unweighted N=1,217). FINDINGS: Nonrefreshing sleep (chi(2)=69.333, p<0.001),
      excessive daytime sleepiness (chi(2)=47.766, p<0.001), and sleep fragmentation
      (chi(2)=30.692, p<0.001) were significantly associated with anxiety.
      Nonrefreshing sleep (OR 3.582, p<0.001) and awakenings due to apneic episodes (OR
      2.047, p=0.001) were predictive of anxiety. CONCLUSION: Comorbid anxiety and OSA
      symptoms are common and have implications for activities of daily living, social
      responsibilities, and quality of life. Screening for anxiety among men with OSA
      symptoms is recommended.

PMID- 24856275
TI  - Work satisfaction and posttraumatic growth 1 year after the 2008 Wenchuan
      earthquake: the perceived stress as a moderating factor.
AB  - This study investigated the role of perceived stress as a possible moderating
      factor between posttraumatic growth (PTG) and work satisfaction. A stratified
      random sampling strategy was used to survey 2080 adult survivors of the 2008
      Sichuan earthquake. The Posttraumatic Growth Inventory, the Job Satisfaction
      Index Scale and the Perceived Stress Scale were used in the assessment of the
      posttraumatic growth, work satisfaction and perceived stress respectively, and
      hierarchical multiple regression analyses were used for the analysis. The
      findings highlight work satisfaction as an important factor in both the
      prediction of posttraumatic growth and for its moderating effect on perceived
      stress. Some demographic characteristics, such as gender, education level, and
      housing condition were found to also affect the survivors' posttraumatic growth.
      This conclusion indicates that managers should pay closer attention to their
      employees' psychological state after a disaster and medical practitioners should
      consider survivors' work status and perceived stress when dispensing mental
      health care.

PMID- 24856276
TI  - Contextual barriers to the successful implementation of family-centered practice
      in mental health care: a Hong Kong study.
AB  - This article presents findings from an exploratory study to identify nurses'
      perspectives on factors that hinder the implementation of family-centered
      practice in mental health settings in Hong Kong. Thirty-four nurses participated
      in the study by completing the pre- and post-questionnaires. Ten nurses were
      invited to participate in focus group and case interviews. The analysis
      identified knowledge-practice gap, role of psychiatric nurses, professional
      identity of psychiatric nurses, and management support as negatively affecting
      the nurses in implementing a family-centered approach to mental health care.
      Suggestions about facilitating the implementation of the family-centered approach
      into clinical practice are offered.

PMID- 24856277
TI  - Challenges faced by Thai families when a loved one has a traumatic brain injury.
AB  - The purpose of this study were to explore challenges and approaches for resolving
      challenges that Thai family members face when engaging with their loved one with
      severe traumatic brain injury in the critical care setting. This pilot study used
      an exploratory design. Nine family members were interviewed at a hospital in
      Thailand. Story-inquiry method guided data collection and analysis. Three
      challenges themes were identified: facing the uncertainty of their loved one's
      illness, dealing with personal sufferings, and changing everyday life patterns.
      Attending to their loved one and attending to self were two themes that family
      members used to manage challenges.

PMID- 24856278
TI  - Necrotizing herpetic retinitis.

PMID- 24856280
TI  - A study on nitroimidazole-99mTc(CO)3 complexes as hypoxia marker: some
      observations towards possible improvement in in vivo efficacy.
AB  - INTRODUCTION: Hypoxia plays a negative role in the clinical management of cancer.
      Detection of hypoxic status of a cancer is important for selecting patients for
      hypoxia directed therapy. Though [(18)F]fluoromisonidazole ([(18)F]FMISO), a PET
      radiopharmaceutical, is presently being used in the clinic for the detection of
      hypoxia, considering the logistical advantages of (99m)Tc and wider availability
      of SPECT scanners, a radiopharmaceutical based on this isotope may find wider
      applicability. METHODS: Nine nitroimidazole (2-, 4- and 5-nitroimidazole) ligands
      were synthesized and radiolabeled using [(99m)Tc(CO)3(H2O)3](+) precursor to
      obtain a group of complexes possessing different single electron reduction
      potential (SERP), overall charge and lipophilicity, the three attributes which
      decide the efficacy of the complex to detect hypoxic cells in vivo. The
      nitroimidazole-(99m)Tc(CO)3 complexes as well as [(18)F]FMISO were evaluated in
      fibrosarcoma tumor bearing mice. RESULTS: The (99m)Tc(CO)3 complexes of
      nitroimidazole iminodiacetic acid (IDA) showed better tumor uptake and retention
      than nitroimidazole diethylenetriamine (DETA) and nitroimidazole
      aminoethylglycine (AEG) complexes. Tumor uptake observed with [(18)F]FMISO was
      higher than any of the nitroimidazole-IDA- (99m)Tc(CO)3 complexes. However,
      [(18)F]FMISO clearance from tumor was found to be faster compared to 2
      nitroimidazole-IDA-(99m)Tc(CO)3 complex. Observed tumor uptake and retention of
      the radiotracers evaluated could be correlated to its blood clearance pattern and
      SERP. CONCLUSIONS: Results of the present study indicated that uptake of the
      radiotracer in tumor is closely associated with its rate of clearance from blood.
      The study also indicated that along with SERP, clearance of radiotracer from
      blood (net effect of charge and lipophilicity) is a critical factor which decides
      the in vivo efficacy of the hypoxia detecting radiopharmaceutical.

PMID- 24856282
TI  - Qualitative cross-cultural exploration of vaginal bleeding/spotting symptoms and
      impacts associated with hormone therapy in post-menopausal women to inform the
      development of new patient-reported measurement tools.
AB  - OBJECTIVES: To understand the vaginal bleeding/spotting experiences of
      postmenopausal (PM) women taking estrogen plus progestin therapies (EPT) and
      develop measures to assess these symptoms and their impact on women's daily lives
      in four countries. DESIGN: (1) Concept elicitation interviews were conducted with
      PM women in the US (n=14), Italy (n=15), Mexico (n=15) and China (n=15) to
      explore vaginal bleeding/spotting symptoms associated with EPT. The Post
      Menopausal Bleeding Questionnaire (PMBQ) was also debriefed to evaluate
      understanding and comprehensiveness. (2) Based on concept elicitation, a single
      item electronic daily diary was developed and the PMBQ modified to form a 12-item
      impact measure. (3) The measures were pilot-tested and then cognitively debriefed
      with US women receiving EPT. All qualitative data was subject to thematic
      analysis. MAIN OUTCOME MEASURES: The Vaginal Bleeding/Spotting Daily Diary, (VBS
      DD) and Post-Menopausal Bleeding Impact Questionnaire (PMBIQ) were developed in
      this study. RESULTS: Concept elicitation identified vaginal bleeding and spotting
      as important symptoms for women taking EPT, impacting their emotional wellbeing,
      social life, ability to move freely, clothing and sexual activity. Based on pilot
      testing and cognitive debriefing, women demonstrated good understanding of the
      VBS-DD and the PMBQ was reduced to 10 items due to conceptual redundancy.
      CONCLUSIONS: Women taking EPT in the US, China, Mexico and Italy reported vaginal
      bleeding/spotting symptoms that have a detrimental impact on their quality of
      life. Two new measures were developed to assess the severity and impact of
      vaginal bleeding/spotting specific to EPT. This work highlights the need for EPT
      related symptoms to be a part of treatment decision-making.

PMID- 24856284
TI  - [Febrile convulsion revealing thrombotic thrombocytopenic purpura].

PMID- 24856281
TI  - Adverse pregnancy outcomes and Coxiella burnetii antibodies in pregnant women,
      Denmark.

PMID- 24856285
TI  - [Cost of multiple sclerosis in France].
AB  - Multiple sclerosis (MS) is one of the 30 chronic conditions specifically listed
      by the French healthcare system as a long-term disease (affections de longue
      duree [ALD]) for which the main health insurance fund (Caisse nationale
      d'assurance maladie des travailleurs salaries [CNAMTS]) provides full (100%)
      coverage of healthcare costs. The CNAMTS insures 87% of the French population
      (52,359,912 of the 60,028,292 inhabitants). The objectives of this study were to
      evaluate the direct and indirect medical costs of MS among the entire population
      insured by the CNAMTS in France in 2004. The CNAMTS provided us with access to
      the ALD database of patients with MS that contains different MS-related
      expenditures made in 2004. We calculated the overall direct and indirect cost of
      MS and the cost per patient and per item of expenditure. In 2004, 49,413 patients
      were registered on the ALD list for MS. Direct cost for MS patients was
      469,719,967 ?. The direct cost per patient and per year was 9,506 ? with
      variations between regions (French administrative divisions) ranging from 10,800
      ? in northeastern France (Champagne-Ardenne) to 8,217 ? in western France (Pays
      de la Loire). The different items of expenditure were treatments (44.5%),
      hospitalization (27.9%), nursing care (5.8%), physiotherapy (5.7%), transport
      (4%), biology (1.1%), and other (1.5%). During the course of the disease, the
      overall cost of MS increased slowly during the first 15 years (from 8,000 to
      11,000 ?), but dramatically the last year of life (23,410 ?). The costs of
      immunomodulator treatments were higher during the first six years after
      registration on the ALD list. Conversely, physiotherapy costs increased linearly
      with time during the course of MS. Indirect costs were an estimated 116 million
      euros in 2004. A disability pension (8,918 ? per patient) was perceived by 9,430
      patients (19.1%) and a daily allowance (3,317 ? per patient) by 9,894 patients
      (20%). In France, MS has an important economic impact, comparable to human
      immunodeficiency virus infection.

PMID- 24856286
TI  - Quantitative analysis of quazepam and its metabolites in human blood, urine, and
      bile by liquid chromatography-tandem mass spectrometry.
AB  - Quazepam (QZP), which is a long-acting benzodiazepine-type hypnotic, and its 4
      metabolites, 2-oxoquazepam, N-desalkyl-2-oxoquazepam (DOQ), 3-hydroxy-2
      oxoquazepam (HOQ), and 3-hydroxy-N-desalkyl-2-oxoquazepam, in human blood, urine,
      and bile were quantitatively analyzed by liquid chromatography-tandem mass
      spectrometry. The analytes were extracted from blood by protein precipitation
      followed by solid phase extraction, and from urine and bile by liquid-liquid
      extraction and cleanup using a PSA solid phase extraction cartridge. This method
      was applied to a medico-legal autopsy case, in which the deceased had been
      prescribed QZP approximately 3 weeks before his death. In blood, the
      concentrations of free DOQ (160+/-7 ng/mL for heart blood and 181+/-12 ng/mL for
      femoral blood) were the highest of all the analytes and in agreement with the
      concentration at a steady state. This indicates that the deceased consecutively
      received QZP for at least several days until the concentrations reached
      approximately the same level as that in the steady state. An extremely high
      concentration of total HOQ (the sum of conjugated and free HOQ) in bile was also
      found (56,200+/-1900 ng/mL). This accumulation of HOQ in bile is probably due to
      enterohepatic circulation. This study demonstrates that the combination of the
      concentrations of QZP and its metabolites in biological matrices can provide more
      information about the amount and frequency of QZP administration.

PMID- 24856288
TI  - Ring-closing metathesis reactions of bis(enynes): selectivity and surprises.
AB  - A study of the ring-closing metathesis reactions of two bis(enynes) is presented.
      These substrates, which contain two alkenes and two alkynes, as well as a
      resident stereocenter, can potentially generate metathesis products resulting
      from many reaction pathways. In this contribution we present our results on these
      reactions, show how small changes in reaction conditions can lead to different
      product ratios, and attempt to provide a rationale for the outcomes. 

PMID- 24856289
TI  - Insular cortex as a mediator of emotion: commentary on emotion and decision
      making explained, by Edmund T. Rolls.

PMID- 24856287
TI  - Effector-triggered defence against apoplastic fungal pathogens.
AB  - R gene-mediated host resistance against apoplastic fungal pathogens is not
      adequately explained by the terms pathogen-associated molecular pattern (PAMP)
      triggered immunity (PTI) or effector-triggered immunity (ETI). Therefore, it is
      proposed that this type of resistance is termed 'effector-triggered defence'
      (ETD). Unlike PTI and ETI, ETD is mediated by R genes encoding cell surface
      localised receptor-like proteins (RLPs) that engage the receptor-like kinase
      SOBIR1. In contrast to this extracellular recognition, ETI is initiated by
      intracellular detection of pathogen effectors. ETI is usually associated with
      fast, hypersensitive host cell death, whereas ETD often triggers host cell death
      only after an elapsed period of endophytic pathogen growth. In this opinion, we
      focus on ETD responses against foliar fungal pathogens of crops. 

PMID- 24856290
TI  - A comprehensive one-pot synthesis of protected cysteine and selenocysteine SPPS
      derivatives.
AB  - A proof-of-principle methodology is presented in which all commercially-available
      cysteine (Cys) and selenocysteine (Sec) solid phase peptide synthesis (SPPS)
      derivatives are synthesized in high yield from easily prepared protected
      dichalcogenide precursors. A Zn-mediated biphasic reduction process applied to a
      series of four bis-N(alpha)-protected dichalcogenide compounds allows facile
      conversion to their corresponding thiol and selenol intermediates followed by
      insitu S- or Se-alkylation with various electrophiles to directly access twenty
      one known Cys and Sec SPPS derivatives. Most of these derivatives were able to be
      precipitated in crude form out of petroleum ether in sufficient purity for direct
      use as peptide building blocks. Subsequent incorporation of these derivatives
      into peptide models nicely illustrates their viability and applicability toward
      SPPS.

PMID- 24856291
TI  - Characterization of a cold-active esterase from Lactobacillus plantarum suitable
      for food fermentations.
AB  - Lactobacillus plantarum is a lactic acid bacteria that can be found in numerous
      fermented foods. Esterases from L. plantarum exert a fundamental role in food
      aroma. In the present study, the gene lp_2631 encoding a putative esterase was
      cloned and expressed in Escherichia coli BL21 (DE3) and the overproduced Lp_2631
      protein has been biochemically characterized. Lp_2631 exhibited optimal esterase
      activity at 20  degrees C and more than 90% of maximal activity at 5  degrees C,
      being the first cold-active esterase described in a lactic acid bacteria. Lp_2631
      exhibited 40% of its maximal activity after 2 h of incubation at 65  degrees C.
      Lp_2631 also showed marked activity in the presence of compounds commonly found
      in food fermentations, such as NaCl, ethanol, or lactic acid. The results suggest
      that Lp_2631 might be a useful esterase to be used in food fermentations. 

PMID- 24856292
TI  - Targeting the olfactory bulb during experimental cerebral malaria.
AB  - Malaria is responsible for over 500 million clinical cases and over 500000 deaths
      annually. Fatalities arise from a range of overlapping syndromes, such as
      cerebral malaria, whose pathogenesis is still incompletely understood. In a new
      study, Coban and colleagues provide new clues on the involvement of the olfactory
      bulb during experimental cerebral malaria in mice that open the way to testable
      hypotheses and potentially earlier intervention in humans. 

PMID- 24856293
TI  - Data from artificial models of mitochondrial DNA disorders are not always
      applicable to humans.

PMID- 24856295
TI  - How steroids steer T cells.
AB  - Recent papers from Mahata et al. and Bereshchenko et al. reveal how steroids
      steer immune responses by tipping T helper (Th) subset balances and activities.
      Pregnenolone produced by Th2 cells mediates immunosuppressive responses, and
      glucocorticoids stimulate regulatory T cell development via the induction of GILZ
      expression.

PMID- 24856294
TI  - Limitations of preimplantation genetic diagnosis for mitochondrial DNA diseases.

PMID- 24856296
TI  - Serum metabolic profiling study of lung cancer using ultra high performance
      liquid chromatography/quadrupole time-of-flight mass spectrometry.
AB  - Lung cancer is currently the leading cause of cancer-related mortality worldwide.
      It is, therefore, important to enhance understanding and add a new auxiliary
      detection tool of lung cancer. In this work, serum metabolic characteristics of
      lung cancer were investigated with a non-targeted metabolomics method. The
      metabolic profiling of 23 patients with lung cancer and 23 healthy controls were
      analyzed using ultra high performance liquid chromatography/quadrupole time of
      flight mass spectrometry (UPLC/Q-TOF MS). Partial least squares discriminant
      analysis (PLS-DA) model of the metabolic data allowed the clear separation of the
      lung cancer patients from the healthy controls. In total, 27 differential
      metabolites were identified, which were mostly related to the perturbation of
      lipid metabolism, including choline, free fatty acids, lysophosphatidylcholines,
      etc. Choline and linoleic acid were defined as one combinational biomarker using
      binary logistic regression, which was supported by the validation with a smaller
      sample-set (9 patients and 9 healthy controls). These findings show that LC/MS
      based serum metabolic profiling has potential application in complementary
      identification of lung cancer patients, and could be a powerful tool for cancer
      research. 

PMID- 24856297
TI  - Non-enzymatic lipid oxidation products in biological systems: assessment of the
      metabolites from polyunsaturated fatty acids.
AB  - Metabolites of non-enzymatic lipid peroxidation of polyunsaturated fatty acids
      notably omega-3 and omega-6 fatty acids have become important biomarkers of lipid
      products. Especially the arachidonic acid-derived F2-isoprostanes are the classic
      in vivo biomarker for oxidative stress in biological systems. In recent years
      other isoprostanes from eicosapentaenoic, docosahexaenoic, adrenic and alpha
      linolenic acids have been evaluated, namely F3-isoprostanes, F4-neuroprostanes,
      F2-dihomo-isoprostanes and F1-phytoprostanes, respectively. These have been
      gaining interest as complementary specific biomarkers in human diseases. Refined
      extraction methods, robust analysis and elucidation of chemical structures have
      improved the sensitivity of detection in biological tissues and fluids.
      Previously the main reliable instrumentation for measurement was gas
      chromatography-mass spectrometry (GC-MS), but now the use of liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) and immunological techniques
      is gaining much attention. In this review, the types of prostanoids generated
      from non-enzymatic lipid peroxidation of some important omega-3 and omega-6 fatty
      acids and biological samples that have been determined by GC-MS and LC-MS/MS are
      discussed.

PMID- 24856298
TI  - Chemo-enzymatic routes to lipopeptides and their colloidal properties.
AB  - A unique chemo-enzymatic route to lipopeptides was demonstrated herein that,
      relative to alternative methods such as solid-phase peptide synthesis (SPPS) and
      microbial synthesis, is simple, efficient, and scalable. Homo- and co
      oligopeptides were synthesized from amino acid ethyl esters via protease
      catalysis in an aqueous media, followed by chemical coupling to fatty acids to
      generate a library of lipopeptides. Synthesized lipopeptides were built from
      hydrophobic moieties with chain lengths ranging from 8 to 18 and peptides
      consisting of oligo(L-Glu) or oligo(L-Glu-co-L-Leu) with an average of seven to
      eight repeating units. The chemical structures of the lipopeptides were
      characterized and confirmed by NMR and matrix-assisted laser
      desorption/ionization (MALDI). The colloidal and interfacial properties of these
      lipopeptides were characterized and compared in terms of the hydrophobic chain
      length, oligopeptide composition, and solution pH. The results showed correlation
      between the interfacial activity of the lipopeptides and the hydrophobicity of
      the fatty acid and oligopeptide headgroup, the effects of which have been
      semiquantitatively described in the manuscript. Results from these studies
      provide insights into design principles that can be further expanded in future
      work to access lipopeptides from protease-catalysis with improved control over
      sequence and exploring a wider range of peptide and lipid compositions to further
      tune lipopeptide biochemical and physical properties.

PMID- 24856299
TI  - [New European policies for air pollution control: a step forward in improving
      public health?].

PMID- 24856301
TI  - An iodine-free and directed-disulfide-bond-forming route to insulin analogues.
AB  - An iodine-free synthetic route to insulin analogues has been established via a
      directed disulfide bond formation strategy. This method is completely compatible
      with oxidation-sensitive residues. The key step is constructing the third
      disulfide bond via a novel procedure involving phenylacetylaminomethyl group
      (Phacm), immobilized Penicillin G Acylase, and Ellman's reagent. We expect that
      this method could be broadly utilized for synthesizing insulin-like and other
      cysteine-rich peptides, in particular, where oxidation-sensitive residues are
      present in the sequence. 

PMID- 24856300
TI  - [Risky alcohol consumption and associated factors in adolescents aged 15 to 16
      years in Central Catalonia (Spain): differences between rural and urban areas].
AB  - OBJECTIVE: To determine the prevalence of risky alcohol consumption and
      associated risk factors among adolescents living in Central Catalonia (Spain)
      during the 2011-2012 academic year, depending on their area of residence. METHOD:
      A cross-sectional study was carried out in a sample of 1268 10th grade students
      (4th grade of secondary education) in Central Catalonia. RESULTS: Risky alcohol
      consumption was higher among adolescents in rural areas than in urban areas
      (59.6% versus 49.8%). Associated risk factors were drunkenness in siblings and
      friends, having positive expectations of alcohol consumption, and buying alcohol.
      Not living with both parents and poorer academic achievement were associated risk
      factors in rural areas, while higher socioeconomic status was a risk factor in
      urban areas. CONCLUSIONS: Risky alcohol consumption was much higher among
      adolescents living in rural areas. The main associated factor was alcohol
      consumption among family and friends.

PMID- 24856303
TI  - Interaction analysis of a ladder-shaped polycyclic ether and model transmembrane
      peptides in lipid bilayers by using Forster resonance energy transfer and
      polarized attenuated total reflection infrared spectroscopy.
AB  - Ladder-shaped polycyclic ethers (LSPs) are predicted to interact with membrane
      proteins; however, the underlying mechanism has not been satisfactorily
      elucidated. It has been hypothesized that LSPs possess non-specific affinity to
      alpha-helical segments of transmembrane proteins. To verify this hypothesis, we
      constructed a model LSP interaction system in a lipid bilayer. We prepared 5
      types of alpha-helical peptides and reconstituted them in liposomes. The
      reconstitution and orientation of these peptides in the liposomes were examined
      using polarized attenuated total reflection infrared (ATR-IR) spectroscopy and
      gel filtration. The results revealed that 4 peptides were retained in liposomes,
      and 3 of them formed stable transmembrane structures. The interaction between the
      LSP and the peptides was investigated using Forster resonance energy transfer
      (FRET). In the lipid bilayer, the LSP strongly recognized the peptides that
      possessed aligned hydrogen donating groups with leucine caps. We propose that
      this leucine-capped 16-amino acid sequence is a potential LPS binding motif. 

PMID- 24856302
TI  - Synthesis and biological evaluation of substituted 3-anilino-quinolin-2(1H)-ones
      as PDK1 inhibitors.
AB  - PDK1 is an important regulator of the PI3K/Akt pathway, which has been found
      frequently activated in a large number of human cancers. Herein we described the
      preparation of novel substituted 3-anilino-quinolin-2(1H)-ones as PDK1
      inhibitors. The synthesis is based around a Buchwald-Hartwig cross-coupling of
      various 3-bromo-6-substituted-quinolin-2(1H)-ones with three different
      functionalised anilines. The modular nature of the designed synthesis allowed
      access to a series of novel inhibitors through derivatisation of a late-stage
      intermediate. All compounds were screened against isolated PDK1 enzyme, with
      modest inhibition observed. 

PMID- 24856304
TI  - New coumarin derivatives: design, synthesis and use as inhibitors of hMAO.
AB  - A series new 2H-chromene-3-carboxamides (4a-4i) and S-2H-chromene-3-carbothioates
      (5j-5t) were synthesized and evaluated as monoamine oxidase A and B inhibitors.
      Among them, compound 5k (IC50=0.21MUM, IC50 iproniazid=7.65MUM) showed the most
      activity and higher MAO-B selectivity (189.2-fold vs 1-fold) with respect to the
      MAO-A isoform. The need to clarify at a 3D level some important molecular aspects
      of discussed SAR, we undertaked a number of docking simulations to better assess.
      The steric effect was analyzed interms of both posing and scoring by
      investigating the nature of the binding interactions. The docking results of
      active compound 5k with hMAO-B complex indicated that conserved residue ILE 199
      was important for ligand binding via Sigma-Pi interaction. 

PMID- 24856305
TI  - Novel synthetic route for antimalarial benzo[a]phenoxazine derivative SSJ-183 and
      two active metabolites.
AB  - A productive synthesis of benzo[a]phenoxazine derivative SSJ-183 (1), a promising
      lead for antimalarial agents, was developed using a one pot procedure.
      Furthermore, N-deethylated metabolite 3 and bis-N,N-deethylated metabolite 4 were
      synthesized by the application of the method. The metabolites 3 and 4 showed
      comparable and ~2-fold increased activities against drug-sensitive and drug
      resistant Plasmodium falciparum parasites. 

PMID- 24856306
TI  - The infrahyoid flap: a comprehensive review of an often overlooked reconstructive
      method.
AB  - The infrahyoid flap is a myocutaneous pedicled flap mainly nourished by the
      superior thyroid vessels through the perforators of the infrahyoid muscles. This
      thin and pliable flap provides a skin island of about 7 by 4 cm from the central
      part of the anterior neck. The flap can be transferred on its pedicle of superior
      thyroid artery and vein to reconstruct medium sized head and neck defects created
      after cancer ablation. We have successfully used this flap in a series of 40
      cases with no total flap loss and with 1 case of superficial skin necrosis. The
      aim of this review is to highlight the clinical usefulness of this pedicled flap
      even in the microvascular free flap era. A comprehensive review of the available
      literature reporting on the infrahyoid flap has been carried out using a web
      search. The history of the infrahyoid flap, the surgical technique with technical
      innovations, the clinical utility and limitations of this flap, are reported and
      discussed. Among the 7 larger series (cohort larger than 50 cases) a total of 956
      flaps were performed, and the global success rate was 91.7%, with failures being
      mainly related to partial skin necrosis, as the rate of total (skin and muscle)
      flap necrosis was only 1%. This flap is reliable, easy to harvest during neck
      dissection, oncologically safe, it does carry a negligible donor site morbidity.
      This paper highlights how the infrahyoid flap can represent an excellent
      reconstructive solution in selected patients and head and neck sites.

PMID- 24856307
TI  - A retrospective review of antebrachial angular and rotational limb deformity
      correction in dogs using intraoperative alignment and type 1b external fixation.
AB  - AIM: The aim of this study was to report the outcome of acute antebrachial
      angular and rotational limb deformity (AARLD) correction using a standard radial
      ostectomy, an unarticulated type 1b external skeletal fixator (ESF) and intra
      operative alignment with no pre-operative planning. METHODS: A retrospective
      evaluation was performed of dogs with carpal valgus, radial procurvatum and
      rotational deformity of the forelimb. All 39 cases presented and were treated
      surgically at a referral hospital in Melbourne, Australia, between September 2008
      and March 2012. Surgical correction involved a standard closing cuneiform radial
      ostectomy, distal ulnar ostectomy and application of an unarticulated type 1b
      ESF. The method used intra-operative limb alignment and did not use pre-operative
      planning. Outcome was assessed via client phone interviews in all cases. Five
      cases were evaluated post-operatively using centre of rotation and angulation
      (CORA) methodology. RESULTS: As reported by owners of the 39 cases following
      surgery, limb function was excellent in 26 (67%), good in 12 (31%) cases and
      acceptable in one (2.5%) case. Frame tolerance was reported as good in 24 (62%),
      acceptable in 14 (36%) cases and poor in one (2.5%) case. Limb appearance was
      reported as straight in 25 (64%) cases and mildly rotated in 14 (36%) cases. In
      five cases that were evaluated, post-operative frontal and sagittal plane
      alignment ranged from 0-3.1 degrees  and 9.1-12.2 degrees , respectively, and
      distal CORA was corrected to <6.1 degrees . These were within the normal reported
      reference ranges. Pin tract infections were reported in seven (18%) cases
      CONCLUSIONS AND CLINICAL RELVANCE: This study suggests that the described
      technique may be an effective practice for the correction of AARLD that provides
      good clinical results, based on client assessment. The effectiveness of this
      technique was further supported by the five cases that underwent objective
      radiographic assessment. The technique is simpler than techniques that use
      extensive pre-operative planning, uses a smaller inventory and is easily
      applicable in companion animal practice.

PMID- 24856308
TI  - Quality of sexual life of women using the contraceptive vaginal ring in extended
      cycles: preliminary report.
AB  - OBJECTIVE: To evaluate the quality of the sexual life of healthy women who are
      using a contraceptive vaginal ring (CVR) in extended cycles. METHODS: Fifty-two
      women (18 to 32 years old) seeking hormonal contraception were enrolled in this
      prospective study. Women were to use a CVR releasing daily 15 MUg of
      ethinylestradiol (EE) and 120 MUg of etonogestrel (ENG) for 63 days, followed by
      a four-day hormone-free interval, for two such extended cycles. At baseline and
      at the first (day 63-73) and second (day 126-134) follow-ups the Female Sexual
      Function Index (FSFI) and the Short Form-36 (SF-36) questionnaires were
      administered to investigate, respectively, sexual behaviour and the quality of
      life (QoL). The Female Sexual Distress Scale (FSDS) was used to verify whether
      sexual dysfunction caused significant personal distress to the woman. RESULTS:
      The FSFI and FSDS scores obtained at the first and second follow-up appointments
      detected an improvement with respect to the baseline score (p < 0.05). QoL
      measures of body pain, general health and emotional role improved at the first
      follow-up visit (p < 0.05); at the second one, all variables showed improvement
      (p < 0.05). CONCLUSION: According to these preliminary data the CVR in extended
      cycles could improve the sexual function and the QoL of women.

PMID- 24856309
TI  - In vitro characterization of Trichophyton rubrum and T. mentagrophytes biofilms.
AB  - Dermatophytes are fungi responsible for a disease known as dermatophytosis.
      Biofilms are sessile microbial communities surrounded by extracellular polymeric
      substances (EPS) with increased resistance to antimicrobial agents and host
      defenses. This paper describes, for the first time, the characteristics of
      Trichophyton rubrum and T. mentagrophytes biofilms. Biofilm formation was
      analyzed by light microscopy, scanning electron microscopy (SEM) and confocal
      laser scanning microscopy (CLSM) as well as by staining with crystal violet and
      safranin. Metabolic activity was determined using the XTT reduction assay. Both
      species were able to form mature biofilms in 72 h. T. rubrum biofilm produced
      more biomass and EPS and was denser than T. mentagrophytes biofilm. The SEM
      results demonstrated a coordinated network of hyphae in all directions, embedded
      within EPS in some areas. Research and characterization of biofilms formed by
      dermatophytes may contribute to the search of new drugs for the treatment of
      these mycoses and might inform future revisions with respect to the dose and
      duration of treatment of currently available antifungals.

PMID- 24856310
TI  - Clinical characteristics of reticular pseudodrusen in the fellow eye of patients
      with unilateral neovascular age-related macular degeneration.
AB  - PURPOSE: To describe associations between reticular pseudodrusen, individual
      characteristics, and retinal function. DESIGN: Cohort study. PARTICIPANTS: We
      recruited 105 patients (age range, 52-93 years) who had advanced neovascular age
      related macular degeneration (AMD) in only 1 eye from 3 clinical centers in
      Europe. METHODS: Minimum follow-up was 12 months. The eye selected for study was
      the fellow eye without advanced disease. Clinical measures of vision were
      distance visual acuity, near visual acuity, and results of the Smith-Kettlewell
      low-luminance acuity test (SKILL). Fundus imaging included color photography, red
      free imaging, blue autofluorescence imaging, fluorescein angiography, indocyanine
      green angiography, and optical coherence tomography using standardized protocols.
      These were used to detect progression to neovascular AMD in the study eye during
      follow-up. All imaging outputs were graded for the presence or absence of
      reticular pseudodrusen (RPD) using a multimodal approach. Choroidal thickness was
      measured at the foveal center and at 2 other equidistant locations from the fovea
      (1500 MUm) nasally and temporally. Metrics on retinal thickness and volume were
      obtained from the manufacturer-supplied automated segmentation readouts. MAIN
      OUTCOME MEASURES: Presence of RPD, distance visual acuity, near visual acuity,
      SKILL score, choroidal thickness, retinal thickness, and retinal volume. RESULTS:
      Reticular pseudodrusen was found in 43 participants (41%) on 1 or more imaging
      method. The SKILL score was significantly worse in those with reticular drusen
      (mean score +/- standard deviation [SD, 38+/-12) versus those without (mean score
      +/- SD, 33+/-9) (P = 0.034). Parafoveal retinal thickness, parafoveal retinal
      volume, and all of the choroidal thickness parameters measured were significantly
      lower in those with reticular drusen than in those without. The presence of RPD
      was associated with development of neovascular AMD when corrected for age and sex
      (odds ratio, 5.5; 95% confidence interval, 1.1-28.8; P = 0.042). All participants
      in whom geographic atrophy developed during follow-up had visible RPD at
      baseline. CONCLUSIONS: Significant differences in retinal and choroidal anatomic
      features, visual function, and risk factor profile exist in unilateral
      neovascular AMD patients with RPD compared with those without; therefore, such
      patients should be monitored carefully because of the risk of developing
      bilateral disease.

PMID- 24856311
TI  - Characterization of punctate inner choroidopathy using enhanced depth imaging
      optical coherence tomography.
AB  - PURPOSE: To perform qualitative and quantitative analyses of retinal and
      choroidal morphology in patients with punctate inner choroidopathy (PIC) using
      enhanced depth imaging optical coherence tomography (EDI-OCT). DESIGN: Cross
      sectional, consecutive series. PARTICIPANTS: A total of 2242 patients attending 2
      tertiary referral uveitis clinics at Moorfields Eye Hospital were screened; 46
      patients with PIC diagnosis were identified, and 35 eyes (35 patients) had
      clinically inactive PIC had EDI-OCT images that met the inclusion criteria.
      METHODS: Punctate inner choroidopathy lesions were qualitatively assessed for
      retinal features, such as (1) focal elevation of the retinal pigment epithelium
      (RPE), (2) focal atrophy of the outer retina/RPE, and (3) presence of sub-RPE
      hyperreflective deposits and choroidal features: (a) presence of focal
      hyperreflective dots in the inner choroid and (b) focal thinning of the choroid
      adjacent to PIC lesions. Quantitative analyses of the retina, choroid, and
      choroidal sublayers were performed, and associations with clinical and
      demographic data were examined. MAIN OUTCOME MEASURES: Prevalence of each lesion
      pattern and thickness of retinal and choroidal layers. RESULTS: A total of 90
      discrete PIC lesions were captured; 46.6% of PIC lesions consisted of focal
      atrophy of the outer retina and RPE; 34.4% consisted of sub-RPE hyperreflective
      deposits; and 18.8% consisted of localized RPE elevation with underlying
      hyporeflective space. Focal hyperreflective dots were seen in the inner choroid
      of 68.5% of patients, with 17.1% of eyes presenting focal choroidal thinning
      underlying PIC lesions. By excluding high myopes, patients with "atypical" PIC
      had reduced retinal thickness compared with patients with "typical" PIC (246.65+/
      30.2 vs. 270.05+/-24.6 MUm; P = 0.04), and greater disease duration was
      associated with decreases in retinal thickness (r = -0.53; P = 0.01). A
      significant correlation was observed between best-corrected visual acuity and
      foveal retinal thickness (r = -0.40; P = 0.03). CONCLUSIONS: In a large series of
      patients with clinically inactive PIC, one fifth of the lesions analyzed revealed
      RPE elevation with underlying hyporeflective space, described before as a sign of
      activity and suggesting subclinical inflammation. Retinal thickness seems to be
      associated with disease type and duration of disease in non-highly myopic eyes.
      Improved visualization of the inner choroid using EDI-OCT may allow noninvasive
      assessment of inflammatory status.

PMID- 24856312
TI  - The sub-occipital transtentorial approach revisited base on our own experience.
AB  - The surgical experience of the sub-occipital approach for treatment of pineal
      gland and pineal region tumors is reported. This approach was originally proposed
      by Jamieson and modified by Lapras who by changing the shape of the bone flap
      obtained the elevation of the occipital lobe which consequently resulted in a
      better exposition of this deep region. The reason why this approach became the
      basis for their treatment is particularly related to the personal experience of
      Lapras who reported his fantastic experience of surgery in this deep area and
      demonstrated the advantages of the sub-occipital transtentorial approach.
      MATERIAL: Out of 277 patients operated from 1982 to 2012 in Lyon for a pineal
      tumor, 233 were treated by a sub-occipital approach: 153 males, 125 females, 75
      patients of pediatric age. The majority of patients were operated on in a sitting
      position which represents a surgical specialty of the anesthesiological school of
      Lyon. RESULTS: Complete tumor removal was possible in 135 patients (58%) and
      partial in 60 patients (26%). For 38 patients, it was not possible to establish
      the quality of surgical resection. The incidence of hemianopsia decreased to less
      that 2% of cases while the incidence of severe pneumocephaly which requires a
      prolonged intensive care hospitalization was less than 4% of cases. Mortality
      related to this surgical approach in the Lyonnais school series was 0% during
      this period. CONCLUSION: In our experience the sub-occipital transtentorial
      approach seems to us the best approach for pineal tumors because it permits a
      large exposition of the pineal region favoring the removal of the tumor with a
      lateral extension and also for tumors extending low into the posterior cranial
      fossa. In fact, this is our preferred approach because it has been used in a
      large majority of cases. However, surgeons have to be familiar with other
      possible approaches to obtain the best result in terms of removal and also to
      decrease the rate of sequelae to improve the quality of life of these patients.

PMID- 24856314
TI  - Tumoral markers in tumors of the pineal region.
AB  - In cases of pineal tumors, a germ cell tumor should always be suspected. As some
      of them are secreting tumors, tumoral markers (AFP and/or hGC) are an important
      part of the diagnostic process. Their positivity either in the serum and/or in
      the cerebrospinal fluid may lead to an accurate diagnosis, avoiding a potentially
      dangerous surgical biopsy. Follow-up of tumoral markers is useful during and
      after treatment in order to monitor response to chemotherapy or a remission
      status. 

PMID- 24856313
TI  - Anatomy of the pineal region applied to its surgical approach.
AB  - INTRODUCTION: The pineal region is situated in the posterior part of the
      incisural space. This region includes the pineal body inside the quadrigeminal
      arachnoidal cistern. This article reviews the anatomic features of this region,
      with particular emphasis on those aspects of importance for surgical access to
      the pineal region. MATERIAL & METHODS: Five cadaver heads fixed in 10% formalin
      and injected with colored latex were used for anatomic dissection (five other
      specimens were also prepared and dissected to illustrate the articles on surgical
      techniques and approaches presented elsewhere in this issue). RESULTS: The pineal
      body is surrounded by several important structures such as: posterior part of the
      third ventricle, tectum, the complex of the great cerebral vein of Galen,
      pulvinar nuclei of the thalamus and splenium of corpus callosum. CONCLUSION: The
      surgical approach of the pineal body, whatever the route or the technique used
      (microsurgical, endoscopic or stereotactic), creates a great challenge for the
      neurosurgeons due to its location in the deep part of the brain and its close
      relationships with complex surrounded vascular structures.

PMID- 24856315
TI  - [The relationship between aneurysmal subarachnoid hemorrhage and meteorological
      parameters based on a series of 236 French patients].
AB  - Subarachnoid hemorrhage (SAH) is a sudden and potentially severe event with
      mortality rates ranging between 24 and 30 % depending on the initial clinical
      condition. Studies have attempted to assess the possible influence of
      meteorological parameters on the occurrence of SAH. However, this idea remains
      very controversial and the results vary widely from one study to another. Our
      study is the second largest French series, and first performed in a homogeneous
      series of patients. The aim of our study was to attempt to establish a
      relationship between the weather (i.e.) temperature variations and daily
      variations of atmospheric pressure in the days before the onset of SAH and the
      same day and the occurrence of non-traumatic SAH in a homogeneous population of
      236 patients from a single center, over a period of 7 years (2002 to 2008). This
      retrospective study does not suggest any relationship between the occurrence of
      SAH and meteorological data studied. Moreover, no relationship was observed
      between mean changes in temperature or pressure and the occurrence of SAH, that
      the day of the bleeding or the days preceding the SAH. However, a female
      predominance was observed and a relatively high mortality rate of 18.3 %. The
      distribution of the occurrence of an SAH was random. As it seems impossible to
      provide logistics and organization of care for non-traumatic SAH, the care system
      must remain vigilant throughout the year.

PMID- 24856317
TI  - Using magnetic resonance imaging to study enzymatic hydrogelation.
AB  - Herein, we report, for the first time, the use of MRI methods to study enzymatic
      hydrogelation. Supramolecular hydrogels have been exploited as biomaterials for
      many applications. However, behaviors of the water molecules encapsulated in
      hydrogels have not been fully understood. In this work, we designed a precursor 1
      which could self-assemble into nanofibers and form hydrogel I (gel I) upon the
      catalysis of phosphatase. The differences of mechanic property, pore size, water
      diffusion rate, and magnetic resonance relaxation times T1 and T2 of gel I
      containing different concentrations of 1 were systematically studied and
      analyzed. T1, T2, and diffusion-weighted (1)H MR images from gel I phantoms were
      obtained at 9.4 T. Analyses of the MRI data uncovered how the density of the
      nanofiber networks affects the relaxation behaviors of the water protons
      encapsulated in such hydrogels. Rheological analyses and cryo-TEM observations
      showed increased gel elasticities with increased concentrations of 1 while the
      pore sizes of gel I decreased. This also resulted in an increase in the proton
      relaxation rate (i.e., shortened T1, T2, and apparent diffusion coefficient
      (ADC)) for the water encapsulated in the hydrogel. With MRI, our study provides a
      new in vitro method to potentially mimic and study in vivo diseases that involve
      fibrous aggregates. 

PMID- 24856316
TI  - Short-stay surgery: what really happens after discharge?
AB  - BACKGROUND: Although duration of hospital stay commonly is used as a surrogate
      outcome for surgical recovery, it is not applicable in the setting of short-stay
      surgery (<24 hours). The objective of our study was to describe the trajectory of
      recovery after short-stay abdominal surgery by using measures of physical
      activity and health-related quality of life (HRQL) and identify predictors of
      prolonged, postdischarge recovery. METHODS: Patients undergoing short-stay
      abdominal surgery were evaluated preoperatively and at 3 weeks and 2 months
      postoperatively. Physical activity was assessed with a validated questionnaire
      (Community Health Activities Model Program for Seniors, ie, CHAMPS) in which
      patients report physical activity for the previous week; responses estimate total
      weekly caloric expenditure (kcal/kg/wk). The Medical Outcomes Study 36-Item Short
      Form Health survey (SF-36) was used to assess HRQL. Multivariate logistic
      regression was performed to determine which variables were predictive of recovery
      to baseline physical activity levels. RESULTS: A total of 132 patients (71% male,
      53 [15] years) participated; 91% were discharged on the day of surgery. The most
      common procedures were open inguinal herniorrhaphy (40%) and laparoscopic
      cholecystectomy (30%). As a group, total, self-reported physical activity and
      most domains of HRQL were recovered to or greater than baseline at 3 weeks
      postoperatively and were above baseline levels at 2 months (P < .01). Patients
      who were older, had a complication, low baseline physical HRQL, or greater
      baseline physical activity were less likely to be recovered to their preoperative
      levels of physical activity at 3 weeks. At 2 months, 33% remained below
      preoperative levels; only high baseline physical activity was an important
      predictor of prolonged recovery. CONCLUSION: Despite uniformly early discharge, a
      substantial proportion of patients (~33%) had suboptimal recovery 2 months after
      short-stay surgery. Measures of physical activity and HRQOL provide complementary
      information and reflect the variability in trajectories of recovery after
      surgery.

PMID- 24856318
TI  - Meta-analysis of randomized clinical trials comparing short-term versus long-term
      dual antiplatelet therapy following drug-eluting stents.
AB  - Current guidelines recommend 12 months of dual antiplatelet therapy (DAPT) after
      drug-eluting stent (DES) implantation in the absence of increased bleeding risk.
      Studies have suggested that early discontinuation of DAPT can result in an
      increased risk of stent thrombosis. However, given the potential for major
      bleeding, the optimal duration of DAPT after DES implantation remains uncertain.
      We searched PubMed, EMBASE, Scopus, and ClinicalTrials.gov databases from
      inception until October 2013 for randomized controlled trials that compared
      shorter versus longer DAPT duration after DES implantation. Four randomized
      controlled trials were included. A total of 4,081 patients received DAPT for 3 to
      6 months, and 4,076 patients were treated with DAPT for 12 to 24 months. Oral
      DAPT consisted of aspirin and clopidogrel. There was no significant difference in
      the rate of the composite outcome of cardiac death or myocardial infarction
      between the short (3.3%) and prolonged (3.0%) DAPT groups (odds ratio 1.11, 95%
      confidence interval 0.87 to 1.43, p=0.41). A landmark analysis performed at the
      time of discontinuation of DAPT in the short DAPT group demonstrated a
      nonsignificant higher rate of stent thrombosis in patients treated with a short
      course of DAPT (0.35% vs 0.20%, p=0.22). Major bleeding was significantly higher
      in the group of patients treated with prolonged DAPT (0.29% vs 0.71%, p=0.01). In
      conclusion, prolonged DAPT compared with short-term treatment is associated with
      increased major bleeding but is not associated with a decrease in the composite
      rates of death or myocardial infarction.

PMID- 24856319
TI  - Meta-analysis of mental stress-induced myocardial ischemia and subsequent cardiac
      events in patients with coronary artery disease.
AB  - Mental stress-induced myocardial ischemia (MSIMI) has been associated with
      adverse prognosis in patients with coronary artery disease (CAD), but whether
      this is a uniform finding across different studies has not been described. We
      conducted a systematic review and meta-analysis of prospective studies examining
      the association between MSIMI and adverse outcome events in patients with stable
      CAD. We searched PubMed, EMBASE, Web of Science, and PsycINFO databases for
      English language prospective studies of patients with CAD who underwent
      standardized mental stress testing to determine presence of MSIMI and were
      followed up for subsequent cardiac events or total mortality. Our outcomes of
      interest were CAD recurrence, CAD mortality, or total mortality. A summary effect
      estimate was derived using a fixed-effects meta-analysis model. Only 5 studies,
      each with a sample size of <200 patients and fewer than 50 outcome events, met
      the inclusion criteria. The pooled samples comprised 555 patients with CAD (85%
      male) and 117 events with a range of follow-up from 35 days to 8.8 years. Pooled
      analysis showed that MSIMI was associated with a twofold increased risk of a
      combined end point of cardiac events or total mortality (relative risk 2.24, 95%
      confidence interval 1.59 to 3.15). No heterogeneity was detected among the
      studies (Q=0.39, I2=0.0%, p=0.98). In conclusion, although few selected studies
      have examined the association between MSIMI and adverse events in patients with
      CAD, all existing investigations point to approximately a doubling of risk.
      Whether this increased risk is generalizable to the CAD population at large and
      varies in patient subgroups warrant further investigation.

PMID- 24856322
TI  - QRS detection using S-Transform and Shannon energy.
AB  - This paper presents a novel method for QRS detection in electrocardiograms (ECG).
      It is based on the S-Transform, a new time frequency representation (TFR). The S
      Transform provides frequency-dependent resolution while maintaining a direct
      relationship with the Fourier spectrum. We exploit the advantages of the S
      Transform to isolate the QRS complexes in the time-frequency domain. Shannon
      energy of each obtained local spectrum is then computed in order to localize the
      R waves in the time domain. Significant performance enhancement is confirmed when
      the proposed approach is tested with the MIT-BIH arrhythmia database (MITDB). The
      obtained results show a sensitivity of 99.84%, a positive predictivity of 99.91%
      and an error rate of 0.25%. Furthermore, to be more convincing, the authors
      illustrated the detection parameters in the case of certain ECG segments with
      complicated patterns. 

PMID- 24856320
TI  - Usefulness of troponin T to predict short-term and long-term mortality in
      patients after hip fracture.
AB  - The purpose was to evaluate the short-term (30-day) and long-term (1,000-day)
      prognostic values of perioperative troponin T (TnT) and electrocardiographic
      (ECG) findings in hip fracture patients. A consecutive cohort of 200 patients (68
      men) was enrolled. Blinded TnT levels and ECG were assessed on admission, before
      operation, and on first and second postoperative days. Median (interquartile
      range) follow-up time was 3.1 (0.3) years. TnT elevation was observed in 71
      patients (35.5%): already before the operation in 36 patients (51%) and only
      after surgery in 35 patients (49%). New ischemic ECG changes were detected in 101
      of 194 patients (52%), including 7 ST elevations. Patients with TnT elevation had
      higher short-term (17% vs 4.7%, respectively, p=0.008) and long-term (61% vs 40%,
      respectively, p=0.005) mortality, the short-term mortality being higher in
      patients with major (TnT>=0.15 MUg/L) compared with minor TnT elevation (24% vs
      13%, respectively, p=0.005). TnT elevation was the only independent predictor of
      short-term mortality (hazard ratio [HR] 3.87, 95% confidence interval [CI] 1.45
      to 10.3, p=0.007), whereas TnT elevation (HR 1.73, 95% CI 1.14 to 2.64, p=0.01),
      increasing age (HR 1.03, 95% CI 1.01 to 1.06, p=0.01), dementia (HR 1.84, 95% CI
      1.22 to 2.78, p=0.004), and atrial fibrillation (HR 1.86, 95% CI 1.18 to 2.93,
      p=0.007) remained independent predictors of long-term mortality. ECG findings
      other than ST elevation did not affect mortality. In conclusion, elevated
      perioperative TnT level is a strong predictor of short-term and long-term
      mortality. Routine TnT measurements and earlier diagnosis together with
      appropriate treatment may improve survival of this fragile patient group.

PMID- 24856323
TI  - Application of chemometric methods to differential scanning calorimeter (DSC) to
      estimate nimodipine polymorphs from cosolvent system.
AB  - The focus of this study was to evaluate the applicability of chemometrics to
      differential scanning calorimetry data (DSC) to evaluate nimodipine polymorphs.
      Multivariate calibration models were built using DSC data from known mixtures of
      the nimodipine modification. The linear baseline correction treatment of data was
      used to reduce dispersion in thermograms. Principal component analysis of the
      treated and untreated data explained 96% and 89% of the data variability,
      respectively. Score and loading plots correlated variability between samples with
      change in proportion of nimodipine modifications. The R(2) for principal
      component regression (PCR) and partial lease square regression (PLS) were found
      to be 0.91 and 0.92. The root mean square of standard error of the treated
      samples for calibration and validation in PCR and PLS was found to be lower than
      the untreated sample. These models were applied to samples recrystallized from a
      cosolvent system, which indicated different proportion of modifications in the
      mixtures than those obtained by placing samples under different storage
      conditions. The model was able to predict the nimodipine modifications with known
      margin of error. Therefore, these models can be used as a quality control tool to
      expediently determine the nimodipine modification in an unknown mixture. 

PMID- 24856324
TI  - Dietary sodium restriction: still searching for the grains of truth.

PMID- 24856325
TI  - Dietary sodium restriction: still searching for the grains of truth. The reply.

PMID- 24856326
TI  - Type 2 myocardial infarction: the next frontier.

PMID- 24856327
TI  - Is uric acid an underdiagnosed mediator of adverse outcome in metabolically
      healthy overweight/obese individuals?

PMID- 24856328
TI  - Seizure occurrence during pediatric short-term EEG.
AB  - AIM: To identify the patients who are more likely to experience a seizure during
      short-term EEG recording. METHODS: We retrospectively reviewed the EEG recordings
      and medical records of 294 patients, who were admitted to the Pediatric
      Departments in Assaf Harofeh Medical Center, and referred for a short-term EEG
      during a 5-years period following a seizure. RESULTS: Fifteen (5.1%) patients had
      seizures during short-term EEG. The likelihood of seizure occurrence was
      increased by history of seizures (odds ratio 11.86, 95% confidence interval 2.54
      55.37), abnormal neurological examination (odds ratio 3.33, 95% confidence
      interval 1.05-10.55), and the presence of interictal epileptiform discharges
      (odds ratio 10.07, 95% confidence interval 1.26-80.42). Treatment with
      antiepileptic drugs and mental retardation were significantly more common among
      patients with seizures. CONCLUSIONS: Children with a higher likelihood of a
      seizure during short-term EEG can be identified using data mainly obtained by
      history and neurological examination.

PMID- 24856331
TI  - Igniting professionalism in your practice.

PMID- 24856332
TI  - A collective purpose for perianaesthesia nursing.

PMID- 24856329
TI  - Insights from the worm: the C. elegans model for innate immunity.
AB  - The nematode worm Caenorhabditis elegans comprises an ancestral immune system. C.
      elegans recognizes and responds to viral, bacterial, and fungal infections.
      Components of the RNA interference machinery respond to viral infection, while
      highly conserved MAPK signaling pathways activate the innate immune response to
      bacterial infection. C. elegans has been particularly important for exploring the
      role of innate immunity in organismal stress resistance and the regulation of
      longevity. Also functions of neuronal sensing of infectious bacteria have
      recently been uncovered. Studies on nematode immunity can be instructive in
      exploring innate immune signaling in the absence of specialized immune cells and
      adaptive immunity. 

PMID- 24856333
TI  - How a JOPAN article saved a patient's life.

PMID- 24856334
TI  - Determining health personnel's application trends of new guidelines for
      preoperative fasting: findings from a survey.
AB  - INTRODUCTION: For over a century, the discontinuation of oral food intake
      preoperatively after midnight has been routinely applied. Although routine
      fasting during the night before elective surgery has been abandoned by many
      modern centers, preoperative fasting after midnight continues as a routine
      practice. PURPOSE: The purpose of this study was to determine trends in health
      personnel's application of new guidelines for preoperative fasting. MATERIALS AND
      METHODS: The research sample of this descriptive study consisted of 73 nurses and
      physicians who were working in the surgical clinics during the time when the
      study was conducted and who agreed to participate in the study. The data of the
      study were collected using a questionnaire designed by the researchers. FINDING:
      Of the health personnel included in the study group, 43.8% routinely kept adult
      patients fasting after midnight, 34.2% discontinued solid food intake 8 hours
      preoperatively, 5.5% discontinued solid food intake 6 hours preoperatively, and
      34.2% discontinued the intake of clear and particulate liquids 4 to 8 hours
      preoperatively. Compliance of the American Society of Anesthesiologists' "2-4-6-8
      rule" by health staff was very low. CONCLUSIONS: This study was carried out in a
      hospital and based on the statements of health staff. Therefore, the findings of
      the study are suggestive in nature and cannot be generalized. We recommend that
      the study should be conducted with larger sample groups and that actual
      preoperative fasting periods of the patients should be determined.

PMID- 24856335
TI  - Clinical utility of an undersized nurse-operated recovery room in the
      postoperative course: results from an Italian community setting.
AB  - PURPOSE: In Europe, standardized criteria for recovery room (RR) requirements
      have not been established. The purpose of this study was to examine the clinical
      utility of an undersized nurse-operated RR in an Italian community hospital.
      DESIGN: Single-center observational study. METHODS: A total of 1,945 consecutive
      surgical patients admitted to the RR at the study institution between September
      31, 2009, and August 31, 2011, were included in the study. A control group of
      surgical patients not admitted to the RR, matched for age, gender, American
      Society of Anesthesiologists score, and type of surgery were also considered. The
      prevalence of early adverse events occurring within 3 hours of the end of surgery
      was compared between the two groups. FINDINGS: Patients admitted to the RR (mean
      age, 73.6 +/- 14.2 years; 42.2% male; and 76.3% having major surgery) showed
      lower prevalences of hypotension (P < .0001), hypertensive response (P < .0001),
      new arrhythmias requiring intervention (P = .0036), and oxygen desaturation (P <
      .0001) in comparison with the control group. No differences in the proportions of
      patients experiencing postoperative nausea and vomiting, shivering, bleeding, and
      respiratory events were found. The Numeric Rating Scale for pain was also
      significantly lower at 2 hours in the study group as compared to the control
      group (1 [0 to 5] vs 3 [1 to 7]; P < .0001). CONCLUSION: In this Italian
      community setting, an undersized nurse-operated RR contributed to a reduced
      prevalence of adverse postoperative events.

PMID- 24856336
TI  - A review of sedation scales for the cardiac catheterization laboratory.
AB  - PURPOSE: Sedation scales have the potential to facilitate effective procedural
      sedation and analgesia in the cardiac catheterization laboratory (CCL). For this
      potential to become realized, a scale that is suitable for use in the CCL either
      needs to be identified or developed. DESIGN: A structured review strategy was
      applied. METHODS: To identify sedation scales, a review of Medline and CINHAL was
      conducted. FINDINGS: One sedation scale for the CCL, the North American Society
      for Pacing and Electrophysiology Sedation Scale, and 15 intensive care unit (ICU)
      scales met the inclusion and exclusion criteria. Analysis of the scale's item
      structures and psychometric properties was then performed. CONCLUSION: None of
      these scales were deemed suitable for use in the CCL. As such, further research
      is required to develop a new scale. The new scale should consist of more than one
      item to make it more effective for tracking the patient's response to
      medications. Specific tests required to conduct a rigorous evaluation of the new
      scale's psychometric properties are outlined in this article.

PMID- 24856337
TI  - Comfort and hope in the preanesthesia stage in patients undergoing surgery.
AB  - PURPOSE: Comfort and hope have been identified as important components in the
      care of perianesthesia patients. The purpose of this study was to explore the
      relationship between comfort and hope in the preanesthesia stage in patients
      undergoing surgery. DESIGN: A descriptive cross-sectional survey was conducted
      with 191 surgical patients. METHODS: Data were collected using the Perianesthesia
      Comfort Questionnaire and Herth Hope Index. FINDINGS: Direct and significant
      relationships were observed between comfort and hope (P<=.001, r=0.65). Also,
      significant relationships were observed between educational level and marital
      status with comfort (P<=.01). The relationship between educational level and hope
      was significant (P<=.001). Significant relationships were also observed between
      gender and marital status with hope (P<=.01). CONCLUSIONS: Overall, this study
      showed that a significant relationship exists between comfort and hope.
      Additionally, some demographic characteristics influenced comfort and hope in
      these patients. Health care providers should arrange the environment in a way
      that allows the surgical patients to experience comfort and hope and recognize
      the impact of personal characteristics when caring for surgical patients,
      particularly in the preanesthesia stage.

PMID- 24856338
TI  - The effect of visiting surgical patients in the postanesthesia care unit on
      family members' anxiety: a prospective quasi-experimental study.
AB  - PURPOSE: Surgical procedures pose stressful events for patients and their family
      members. The main purpose of this study was to determine if visiting patients in
      the postanesthesia care unit (PACU) would reduce the anxiety levels of Greek
      patients' family members. DESIGN: A prospective study with a one-group quasi
      experimental pretest/post-test design was used. METHODS: Situational anxiety of
      surgical patients' relatives was assessed using the state subscale of the State
      Trait Anxiety Inventory (STAI; Greek validation) at the beginning of the surgical
      procedure and again after their visitation of patients in the PACU. FINDINGS:
      STAI scores were significantly higher preoperatively (57 [23-80]) than
      postoperatively (51 [21-77]; P=.000008). Clinically significant levels of anxiety
      were present in 76% and 58% of the participants, pre- and postoperatively,
      respectively. CONCLUSIONS: Although postoperative STAI scores were reduced,
      family visitation in the PACU did not sufficiently reduce the anxiety of Greek
      family members to clinically acceptable levels.

PMID- 24856339
TI  - Deep brain stimulation for Parkinson's disease.

PMID- 24856340
TI  - Measuring the safety of writing on intravenous bags.

PMID- 24856341
TI  - The racist patient--revisited.

PMID- 24856342
TI  - Engaged: the potentially rocky marriage of patients and their digital data.

PMID- 24856343
TI  - One size does not fit all: opioid dose range orders.

PMID- 24856345
TI  - Global perianesthesia research: embrace the possibilities.

PMID- 24856344
TI  - Anesthetic drugs and malignant hyperthermia.

PMID- 24856346
TI  - Palladium-catalyzed synthesis of heterocycle-containing diarylmethanes through
      Suzuki-Miyaura cross-coupling.
AB  - The heterocycle-containing diarylmethane synthesis from
      chloromethyl(hetero)arenes with (hetero)arylboron reagents was attained using the
      palladium/ether-imidazolium chloride system. This coupling process tolerated a
      diverse range of heteroaromatic moieties with sufficient catalytic activity to
      achieve the efficient synthesis of various diheteroarylmethanes in good to
      excellent yields. 

PMID- 24856347
TI  - Genetic susceptibility to the cross-reactivity of aromatic antiepileptic drugs
      induced cutaneous adverse reactions.
AB  - BACKGROUND: The cross-allergic reactions among aromatic antiepileptic drugs
      (AEDs) are common, but little is known about the genetic mechanisms. PURPOSE: The
      aim of this study was to investigate the genetic associations of the human
      leukocyte antigen (HLA) genes with the cross-reactivity of cutaneous adverse drug
      reactions (cADRs) induced by different aromatic AEDs. METHODS: We reviewed 60
      Chinese patients with a history of cADRs induced by an aromatic AED, and which re
      challenged other aromatic AEDs as an alternative to the causative AED owing to
      some particular reasons. According to whether developing another episode of
      cADRs, these patients were automatically divided into the cross-reactivity group
      and tolerant control group. High-resolution HLA-A, -B, -DRB1 genotyping were
      performed for each patient. RESULTS: One out of 10 patients (10%, 1/10) carried
      the HLA-A*2402 allele in the cross-reactivity group. However, 23 patients (46%,
      23/50) carried this allele in the tolerant control group. The difference of the
      HLA-A*2402 allele between the two groups is statistically significant (P=0.040,
      OR=0.130, 95% CI: 0.015-1.108). In addition, the frequency differences of other
      HLA alleles between the two groups, including the HLA-B*1502 allele, did not
      reach statistical significance (P>0.05). CONCLUSIONS: The HLA genes contribute to
      the genetic susceptibility of the cross-reactivity of cADRs among aromatic AEDs.
      Our results suggest that HLA-B*1502 is not a major responsible allele for the
      cross-reactivity of cADRs to aromatic AEDs, but the HLA-A*2402 allele may be a
      protective marker for the cross-allergic reactions among aromatic AEDs in Han
      Chinese. Further studies are warranted to test the potential predictive value of
      the HLA-A*2402 allele in future.

PMID- 24856355
TI  - Synthesis of a thin-layer MnO2 nanosheet-coated Fe3O4 nanocomposite as a
      magnetically separable photocatalyst.
AB  - A facile hydrothermal method combined with a mild ultrasonic means has been
      developed for the fabrication of a magnetically recyclable thin-layer MnO2
      nanosheet-coated Fe3O4 nanocomposite. The photocatalytic studies suggest that the
      MnO2/Fe3O4 nanocomposite shows excellent photocatalytic efficiency and stability
      simultaneously for the degradation of methylene blue under UV-vis light
      irradiation. Moreover, its good acid resistance and stable recyclability are very
      important for its future practical application as a photocatalyst. Magnetic
      measurements verify that the MnO2/Fe3O4 nanocomposite possesses a ferromagnetic
      nature, which can be effectively separated for reuse by simply applying an
      external magnetic field after the photocatalytic reaction. This novel composite
      material may have potential applications in water treatment, degradation of dye
      pollutants, and environmental cleaning. 

PMID- 24856348
TI  - Genetic Evidence of Importation of Drug-Resistant Plasmodium falciparum to
      Guatemala from the Democratic Republic of the Congo.
AB  - Imported malaria threatens control and elimination efforts in countries that have
      low rates of transmission. In 2010, an outbreak of Plasmodium falciparum malaria
      was reported among United Nations peacekeeping soldiers from Guatemala who had
      recently returned from the Democratic Republic of the Congo (DRC). Epidemiologic
      evidence suggested that the soldiers were infected in the DRC, but local
      transmission could not be ruled out in all cases. We used population genetic
      analyses of neutral microsatellites to determine the outbreak source. Genetic
      relatedness was compared among parasites found in samples from the soldiers and
      parasite populations collected in the DRC and Guatemala; parasites identified in
      the soldiers were more closely related to those from the DRC. A phylogenetic
      clustering analysis confirms this identification with >99.9% confidence. Thus,
      results support the hypothesis that the soldiers likely imported malaria from the
      DRC. This study demonstrates the utility of molecular genotyping in outbreak
      investigations. 

PMID- 24856358
TI  - The project connect health systems intervention: linking sexually experienced
      youth to sexual and reproductive health care.
AB  - PURPOSE: To evaluate a health systems intervention to increase adolescents'
      receipt of high-quality sexual and reproductive health care services. METHODS:
      Quasi experimental design. Twelve high schools in a large public school district
      were matched into pairs. Within each pair, schools were assigned to condition so
      that no control school shared a geographic border with an intervention school.
      Five yearly surveys (T1, T2, ..., T5) were administered from 2005 to 2009 (N =
      29,823) to students in randomly selected classes in grades 9-12. Community-based
      providers of high-quality sexual and reproductive health care services were
      listed on a referral guide for use by school nurses to connect adolescents to
      care. RESULTS: Statistically significant effects were found for intervention
      school females on three outcomes, relative to controls. Relative to T1, receipt
      of birth control in the past year was greater at T4 (adjusted odds ratio [AOR] =
      1.85; 95% confidence interval [CI], 1.09-3.15) and T5 (AOR = 2.22; 95% CI, 1.32
      3.74). Increases in sexually transmitted disease testing and/or treatment in the
      past year were greater in T1-T3 (AOR = 1.78; 95% CI, 1.05-3.02), T1-T4 (AOR =
      1.73; 95% CI, 1.01-2.97), T1-T5 (AOR = 1.97; 95% CI, 1.17-3.31), and T2-T5 (AOR =
      1.76; 95% CI, 1.06-2.91). Increases in ever receiving an HIV test were greater in
      T1-T4 (AOR = 2.14; 95% CI, 1.08-4.26). Among males, no intervention effects were
      found. CONCLUSIONS: A school-based structural intervention can improve female
      adolescents' receipt of services.

PMID- 24856360
TI  - Imaging of the optic disk in caring for patients with glaucoma: ophthalmoscopy
      and photography remain the gold standard.
AB  - Optic disk imaging is integral to the diagnosis and treatment of patients with
      glaucoma. We discuss the various forms of imaging the optic nerve, including
      ophthalmoscopy, photography, and newer imaging modalities, including optical
      coherence tomography (OCT), confocal scanning laser ophthalmoscopy (HRT), and
      scanning laser polarimetry (GDx), specifically highlighting their benefits and
      disadvantages. We argue that ophthalmoscopy and photography remain the gold
      standard of imaging due to portability, ease of interpretation, and the presence
      of a large database of images for comparison. 

PMID- 24856359
TI  - [Abdominal pain, weight loss and asthenia in a 42-year-old man].

PMID- 24856361
TI  - Pharmacokinetic evaluation of pegaptanib octasodium for the treatment of diabetic
      edema.
AB  - INTRODUCTION: Diabetic macular edema (DME) is a leading cause of visual
      impairment in patients with diabetic retinopathy. Pegaptanib octasodium (Macugen)
      was the first anti-VEGF agent approved for the treatment of neovascular age
      related macular degeneration. It is a selective anti-VEGF agent, which only
      blocks VEGF. It has been shown to be safe and effective in treatment of DME in
      randomized controlled trials and it may be a safer first-line treatment in
      patients with diabetes with a predisposition to cardiovascular risk factors.
      AREAS COVERED: This review covers the pharmacokinetics of pegaptanib octasodium.
      The authors also evaluate pegaptanib octasodium's clinical efficacy, safety and
      tolerability in DME. EXPERT OPINION: DME is the most common cause of visual loss
      in patients with diabetes. Pegaptanib has been found to be more effective than
      laser therapy alone for center-involving DME, its efficacy might be slightly
      worse than other pan-VEGF blockers, but the number of patients that have
      significant improvement of vision after treatment are similar to those treated
      with pan-VEGF blockers. As a selective VEGF blocker, it may have a better ocular
      and systemic safety profile than pan-VEGF blocking agents. It is reasonable to
      consider pegaptanib as the first-line treatment for center-involving DME with pan
      VEGF blockers reserved for non-responders.

PMID- 24856362
TI  - Structural basis for the inhibition of host protein ubiquitination by Shigella
      effector kinase OspG.
AB  - Shigella invasion of its human host is assisted by T3SS-delivered effector
      proteins. The OspG effector kinase binds ubiquitin and ubiquitin-loaded E2
      conjugating enzymes, including UbcH5b and UbcH7, and attenuates the host innate
      immune NF-kB signaling. We present the structure of OspG bound to the UbcH7~Ub
      conjugate. OspG has a minimal kinase fold lacking the activation loop of
      regulatory kinases. UbcH7~Ub binds OspG at sites remote from the kinase active
      site, yet increases its kinase activity. The ubiquitin is positioned in the
      "open" conformation with respect to UbcH7 using its I44 patch to interact with
      the C terminus of OspG. UbcH7 binds to OspG using two conserved loops essential
      for E3 ligase recruitment. The interaction of the UbcH7~Ub with OspG is
      remarkably similar to the interaction of an E2~Ub with a HECT E3 ligase. OspG
      interferes with the interaction of UbcH7 with the E3 parkin and inhibits the
      activity of the E3. 

PMID- 24856364
TI  - Trauma-related shame and guilt as time-varying predictors of posttraumatic stress
      disorder symptoms during imagery exposure and imagery rescripting--A randomized
      controlled trial.
AB  - OBJECTIVE: The specific aims of this study are to examine trauma-related shame
      and guilt as time-varying predictors of symptoms of posttraumatic stress disorder
      (PTSD). METHOD: Sixty-five patients were included in the statistical analyses and
      the multilevel modeling analyses supported three major findings. RESULTS: (i)
      Patients with a higher level of shame and guilt at the start of treatment
      displayed a higher level of PTSD symptoms over the course of treatment compared
      to other patients. (ii) Time-specific change in shame and guilt predicted the
      level of PTSD symptoms 3 days later from session to session during treatment.
      (iii) No significant differences were evident between prolonged exposure (PE) and
      modified PE to include imagery rescripting in the within-person process of change
      in PTSD symptoms from session to session during therapy. CONCLUSIONS: This trial
      reports the first evidence that within-person change in shame and guilt predicts
      change in PTSD symptoms from session to session during treatment.

PMID- 24856363
TI  - Random single amino acid deletion sampling unveils structural tolerance and the
      benefits of helical registry shift on GFP folding and structure.
AB  - Altering a protein's backbone through amino acid deletion is a common
      evolutionary mutational mechanism, but is generally ignored during protein
      engineering primarily because its effect on the folding-structure-function
      relationship is difficult to predict. Using directed evolution, enhanced green
      fluorescent protein (EGFP) was observed to tolerate residue deletion across the
      breadth of the protein, particularly within short and long loops, helical
      elements, and at the termini of strands. A variant with G4 removed from a helix
      (EGFP(G4Delta)) conferred significantly higher cellular fluorescence. Folding
      analysis revealed that EGFP(G4Delta) retained more structure upon unfolding and
      refolded with almost 100% efficiency but at the expense of thermodynamic
      stability. The EGFP(G4Delta) structure revealed that G4 deletion caused a
      beneficial helical registry shift resulting in a new polar interaction network,
      which potentially stabilizes a cis proline peptide bond and links secondary
      structure elements. Thus, deletion mutations and registry shifts can enhance
      proteins through structural rearrangements not possible by substitution mutations
      alone. 

PMID- 24856365
TI  - Comparison of the performance of the NucliSENS EasyQ HPV E6/E7 mRNA assay and HPV
      DNA chip for testing squamous cell lesions of the uterine cervix.
AB  - This study aims to evaluate the clinical performance of the NucliSENS EasyQ assay
      and compare it with HPV DNA genotyping for the detection of high-grade squamous
      intraepithelial lesions (HSIL) and cancer in a Korean population. In 188 total
      thin prep samples, the remaining fluid after cytology slide preparation was
      tested with Goodgene HPV DNA chips and the NucliSENS EasyQ HPV E6/E7 messenger
      RNA (mRNA) assay. The sensitivity and specificity of each test were calculated
      with HSIL and squamous cell carcinoma (SCC) as the disease endpoint. Out of the
      188 samples, 139 (74%) were positive for DNA of 14 HPV types, while 57 (30%)
      cases were positive for E6/E7 mRNA. The DNA test was positive in cytology cases
      of SCC, HSIL, and atypical squamous cell. The mRNA test yielded results of 75%,
      74%, 60%, 56%, and 29% positivity in abnormal cytology cases of SCC, HSIL,
      atypical squamous cells - cannot exclude HSIL, atypical squamous cells of
      undetermined significance, and low-grade squamous intraepithelial lesion,
      respectively. In normal cytology cases, the positivity rates were 9% and 53% for
      the mRNA and DNA tests, respectively. For detection of HSIL and SCC, the
      sensitivity of the mRNA test was 74.36% and that of the DNA test was 100%, while
      the specificities of the tests were 85% and 40.83%, respectively. These findings
      suggest that the HPV E6/E7 mRNA assay can overcome the shortcoming of low
      specificity of DNA assays for clinical detection of high-grade cervical lesions
      and malignancies. 

PMID- 24856367
TI  - [An exceptional cervicomediastinal mass in a child].

PMID- 24856368
TI  - [Recurrent tracheoesophageal fistula in type III esophageal atresia. Diagnosis
      and treatment are not easy].
AB  - Recurrent tracheoesophageal fistula (TEF) is possible after repair of congenital
      esophageal atresia. The frequency of recurrent TEF is observed in about 10% of
      the cases. Within a cohort of 67 children with type III esophageal atresia
      repaired between 1998 and 2009, we aimed to identify the number of children with
      recurrent TEF, the risk factors for this condition, and the treatment proposed.
      The sex ratio was 1.7. Surgery was performed between 4 and 36 hours of life. Five
      children (7.5%) had a recurrent TEF, usually during the first 3 months, revealed
      by respiratory symptoms related to feeding in some cases. We noted that recurrent
      TEF was more frequent with anastomotic leakage (P=0.09) or postsurgical
      pneumothorax (P<0.01). The diagnosis was made in four cases out of five by a
      methylene blue test performed during a tracheobronchial endoscopy. Surgical
      treatment was noted in four children, with three postsurgical secondary effects.
      One child was treated by endoscopy and an esophageal clip. With a median follow
      up of 52 months, no recurrence was noted. The recurrence of TEF may be linked to
      postsurgical events. Diagnosis is not easy and treatment is not clearly codified.
      Endoscopic treatment may be an advantageous option to surgery, likely with less
      morbidity.

PMID- 24856369
TI  - Superficial siderosis of the central nervous system as a presentation of stage iv
      melanoma.

PMID- 24856370
TI  - Efficacy of manual therapy in the treatment of tension-type headache. A
      systematic review from 2000-2013.
AB  - OBJECTIVES: To study the efficacy of manual therapy in the treatment of tension
      type headache (TTH) by assessing the quality of randomized control trials (RCTs)
      published from the year 2000 to April 2013. METHODS: A search was performed in
      the following databases: MEDLINE, EBSCO, CINAHL, SCOPUS, PEDRO and OVID. An
      analysis was made of RCT including patients with TTH receiving any manual
      therapy, and assessing outcome measures including the intensity, and frequency or
      duration of the headache. Two independent referees reviewed the methodological
      quality of RCTs using the Jadad scale. Data from the studies were extracted by
      two different reviewers. RESULTS: A total of fourteen RCTs were selected. Twelve
      studies showed acceptable quality (Jadad scale >=3), and the remaining 2 had low
      quality (Jadad=2). The studies showed positive results, including reduction in
      headache intensity and/or frequency, reduction of medication consumption, and
      improvement in quality of life. CONCLUSIONS: The effectiveness of manual therapy
      for TTH cannot be completely assessed due to the heterogeneity in study design,
      outcome measures, and different treatments. Nevertheless, the results suggest
      patients with TTH receiving manual therapies showed better progress than those
      receiving conventional treatment or placebo. Further studies of high quality
      using manual therapy protocols, and also including standardized outcome measures,
      are now needed to clarify the efficacy of manual therapy in the management of
      TTH.

PMID- 24856371
TI  - In vivo injectable human adipose tissue regeneration by adipose-derived stem
      cells isolated from the fluid portion of liposuction aspirates.
AB  - Liposuction aspirates separate into fatty and fluid portions. Cells isolated from
      the fatty portion are termed processed lipoaspirate (PLA) cells and isolated from
      the fluid portion termed liposuction aspirate fluid (LAF) cells, both of which
      contain adipose-derived stromal cells (ASCs). Here, we examined the biological
      differences between PLA and LAF cells and then tested the differentiation
      capacity of LAF cells in vivo. The cell surface marker and the multiple
      differentiation ability of fresh isolated PLA and LAF cells and which from
      passaged 3-5 were examined in vitro. LAF cells were then incubated in adipogenic
      medium, stained with 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine
      (DiI), mixed with fibrin glue then injected to nude mice; fibrin glue without
      cells was as a control. Three months later, the transplants were subjected to
      macroscopic observation and histological analysis. PLA and LAF cells were similar
      in growth kinetics, morphology, capacity for differentiation, and surface marker
      profiles. After plating, both PLA and LAF cells showed increased expression of
      CD29, CD44, CD133 and HLA DR and decreased expression of CD34. In vivo
      differentiation assay showed the mixture of LAF cells and fibrin glue formed
      adipose tissue which contained red fluorescent DiI-positive adipocytes. LAF cells
      can be harvested more easily than PLA cells. The in vivo adipogenic capacity
      suggested LAF cells would be useful and valuable for cell-based therapies and
      soft tissue reconstruction. 

PMID- 24856372
TI  - Potential adverse effects to the retina of cancer therapy targeting pyruvate
      kinase M2.

PMID- 24856373
TI  - Novel human bufavirus genotype 3 in children with severe diarrhea, Bhutan.
AB  - We identified a new genotype of bufavirus, BuV3, in fecal samples (0.8%)
      collected to determine the etiology of diarrhea in children in Bhutan. Norovirus
      GII.6 was detected in 1 sample; no other viral diarrheal pathogens were detected,
      suggesting BuV3 as a cause of diarrhea. This study investigates genetic diversity
      of circulating BuVs. 

PMID- 24856374
TI  - Circadian rhythmicity and photic plasticity of myosin gene transcription in fast
      skeletal muscle of Atlantic cod (Gadus morhua).
AB  - The circadian rhythm is a fundamental adaptive mechanism to the daily
      environmental changes experienced by many organisms, including fish. Myosins
      constitute a large family of contractile proteins that are essential functional
      components of skeletal muscle. They are known to display thermal plasticity but
      the influence of light on myosin expression remains to be investigated in fish.
      In the present study, we have examined the circadian rhythmicity and
      photoperiodic plasticity of myosin gene transcription in Atlantic cod (Gadus
      morhua) fast skeletal muscle. In silico mining of the Atlantic cod genome
      resulted in the identification of 76 myosins representing different classes, many
      of which were hitherto uncharacterized. Among the 23 fast skeletal muscle myosin
      genes, myh_tc, myh_n1, myh_n4, myo18a_2, and myo18b_2 displayed circadian
      rhythmic expression and contained several circadian-related transcription factor
      binding sites (Creb, Mef2 and E-box motifs) within their putative promoter
      regions. Also, the circadian expression of these 5 myosins strongly correlated
      with the transcription pattern of clock genes in fast skeletal muscle. Under ex
      vivo conditions, myosin transcript levels lost their circadian rhythmicity.
      Nonetheless, different photoperiod regimes influenced the mRNA levels of myh_n4,
      myo18a_2 and myo18b_2 in fast skeletal muscle explants. Photoperiod manipulation
      in Atlantic cod juveniles revealed that continuous light significantly elevated
      mRNA levels of several myosins in fast skeletal muscle when compared to natural
      photoperiod. The daily rhythmicity observed in some fast skeletal muscle myosin
      genes suggests that they may be under circadian clock regulation. In addition,
      the influence of photoperiod on their expression implies that myosins may be
      involved in the photic plasticity of muscle growth observed in Atlantic cod. 

PMID- 24856375
TI  - Oxidative stress status in elite athletes engaged in different sport disciplines.
AB  - Exercise training may increase production of free radicals and reactive oxygen
      species in different ways. The training type and intensity may influence free
      radicals production, which leads to differences in oxidative stress status
      between athletes, but the results of the previous studies are incosistent. The
      aim of our study was to estimate oxidative stress status in elite athletes
      engaged in different sport disciplines. The study included 39 male highly skilled
      professional competitors with international experience (2 Olympic players): 12
      wrestlers, 14 soccer players and 13 basketball players in whom we determined the
      levels of advanced oxidation protein products (AOPP) and malondialdehyde (MDA),
      as markers of oxidative stress and the total antioxidative capacity (ImAnOX)
      using commercially available assay kits. The mean AOPP concentration was not
      significantly different between soccer players, wrestler and basketball players
      (60.0 +/- 23.0 vs. 68.5 +/- 30.8 and 80.72 +/- 29.1 MUmol/L respectively). Mean
      ImAnOX concentration was not different between soccer players (344.8 +/- 35.6
      MUmol/L), wrestlers (342.5 +/- 36.2 MUmol/L) and basketball players (347.95 +/-
      31.3 MUmol/L). Mean MDA concentration was significantly higher in basketball
      players (1912.1 +/- 667.7 ng/mL) compared to soccer players (1060.1 +/- 391.0
      ng/mL, p=0.003). In spite of this fact, oxidative stress markers levels were
      increased compared to referral values provided by the manufacturer. Type of
      sports (soccer, wrestler or basketball) have no impact on the levels of oxidative
      stress markers. Elite sports engagement is a potent stimulus of oxidative stress
      that leads to the large recruitment of antioxidative defense. Oxidative stress
      status monitoring followed by appropriate use of antioxidants is recommended as a
      part of training regime.

PMID- 24856376
TI  - Cyclooxygenase-2 inhibition improves antioxidative defense during experimental
      hypercholesterolemia.
AB  - Scientific literature shows that inflammation and oxidative stress contribute in
      the pathogenesis of atherosclerosis. The oxidative stress is the consequence of
      an imbalance between the free radical generation and elimination. One source of
      free oxygen radicals is cyclooxygenase (COX)-2 and, therefore, inhibiting the
      activity of this enzyme is likely to reduce oxidative stress. In the present
      study an experimental rabbit model of hypercholesterolemia was developed and the
      effects of COX-2 inhibitors, nimesulide and celecoxib were observed on the
      activities of antioxidant enzymes, superoxide dismutase (SOD), glutathione
      peroxidase (GPx) and total antioxidant status (TAS). Rabbits were divided into
      four groups- control, saline, nimesulide and celecoxib, with all groups fed a
      high cholesterol diet, which only received saline. Low activities of SOD, GPx and
      TAS were measured in the hypercholesterolemic rabbits pretreated with saline. In
      the same group, a reciprocal relationship was observed between the LDL
      cholesterol concentration and the plasma activities of GPx, SOD and TAS. Rabbits
      in nimesulide and celecoxib group showed significantly higher activities of SOD,
      GPx and TAS in hypercholesterolemic rabbits compared to saline group (p<0.05).
      Our study shows that selective and timely use of COX-2 inhibitors would be useful
      in preventing the onset and development of atherosclerosis by enhancing
      antioxidant defence system.

PMID- 24856377
TI  - Changes in activated partial thromboplastin time and international normalised
      ratio after on-pump and off-pump surgical revascularization of the heart.
AB  - Surgical revascularization of the heart (CABG - coronary artery bypass grafting)
      is one way of treating coronary heart disease. Bleeding is one of the serious and
      frequent complications of heart surgery and can result in increased mortality and
      morbidity. Hemostasis disorder may be secondary consequences of surgical
      bleeding, preoperative anticoagulant therapy, and the use of cardiopulmonary
      bypass. Tests used for routine evaluation of the coagulation system are activated
      partial thromboplastin time (APTT) and international normalized ratio (INR). The
      study encountered 60 patients who were hospitalized at the Clinic for
      Cardiovascular Diseases, University Clinical Center Tuzla. Patients underwent
      elective coronary artery bypass heart surgery either with cardiopulmonary bypass
      (on-pump CABG) or without it (off-pump CABG). The aim of this study was to
      compare the changes in coagulation tests (APTT, INR) in patients who were
      operated on-pump and patients operated off-pump. Our study showed that the values
      of APTT and INR tend to increase immediately after surgery. Twenty-four hours
      after surgery these values are declining and they are approaching the
      preoperative values in all observed patients (p <0.05). Comparing APTT between
      the groups we found that postoperative APTT levels are significantly higher in
      the group of patients who underwent surgery with cardiopulmonary bypass (p
      <0.05). Changes in coagulation tests after surgical revascularization of the
      heart are more pronounced in patients who were operated with on-pump technique
      compared to patients operated off-pump technique.

PMID- 24856378
TI  - Effect of met-enkephalin on chromosomal aberrations in the lymphocytes of the
      peripheral blood of patients with multiple sclerosis.
AB  - Endogenious opiod met-enkephalin throughout previous research manifested
      cytoprotective and anti-inflammatory effects. Previous research suggests that met
      enkephalin has cytogenetic effects. Reducement in the frequency of structural
      chromosome aberrations as well as a suppressive effect on lymphocyte cell cycle
      is found. It also reduces apoptosis in the blood samples of the patients with
      immune-mediated diseases. Met-enkephalin exerts immunomodulatory properties and
      induces stabilization of the clinical condition in patients with multiple
      Sclerosis (MS). The goal of the present research was to evaluate met-enkephalin
      in vitro effects on the number and type of chromosome aberrations in the
      peripheral blood lymphocytes of patients with MS. Our research detected
      disappearance of ring chromosomes and chromosome fragmentations in the cultures
      of the peripheral blood lymphocytes treated with met-enkephalin (1.2 MUg/mL).
      However, this research did not detect any significant effects of met-enkephalin
      on the reduction of structural chromosome aberrations and disappearance of
      dicentric chromosomes. Chromosomes with the greatest percent of inclusion in
      chromosome aberrations were noted as: chromosome 1, chromosome 2 and chromosome
      9. Additionally, we confirmed chromosome 14 as the most frequently included in
      translocations. Furthermore, met-enkephalin effects on the increase of the
      numerical aberrations in both concentrations applied were detected. Those
      findings should be interpreted cautiously and more research in this field should
      be conducted.

PMID- 24856379
TI  - Is minimally invasive application by intramedullary osteosynthesis in comparison
      with volar plating real benefit in the treatment of distal radius fractures?
AB  - PURPOSE OF THE STUDY: Can minimally invasive intramedullary osteosynthesis of
      distal radius fractures provide better therapeutic results than multidirectional
      locking plates. Retrospective study of 68 patients operated for distal radius
      fractures, 18 were treated with intramedullary X-screw (XSCR) fixation and 50
      with the multidirectional angle-stable plate system (APTUS). The evaluation at 1
      year follow-up included functional status of the wrist and hand, and radiographic
      findings. In the XSCR group, the functional outcomes of the treated extremity did
      not achieve values comparable with those of the uninjured side in any of the
      parameters measured. The radiographic findings did not meet the requirements of
      successful healing due to failure to restore an anatomical volar tilt in 22.2%
      cases. In the APTUS group, comparable values of the injured and the uninjured
      side were achieved in radial deviation, ulnar deviation, pronation, supination
      and grip strength. The radiographic criteria of successful healing were met by
      all fractures treated by locking plate osteosynthesis. Implant migration
      associated with secondary displacement of bone fragments was recorded in 33.3 %
      of the XSCR patients and only in 4.0 % of the APTUS patients. The overall
      evaluation show that intramedullary osteosynthesis does not produce better
      treatment outcomes compared with plate osteosynthesis in indicated types of
      fractures.

PMID- 24856381
TI  - A comparative analysis of the effectiveness of cytogenetic and molecular genetic
      methods in the detection of Down syndrome.
AB  - The goal of this study was to examine the effectiveness of 6 STR markers
      application (D21S1435, D21S11, D21S1270, D21S1411, D21S226 and IFNAR) in
      molecular genetic diagnostics of Down syndrome (DS) and to compare it with
      cytogenetic method. Testing was performed on 73 children, with the previously
      cytogenetically confirmed Down syndrome. DNA isolated from the buccal swab was
      used. Previously mentioned loci located on chromosome 21 were simultaneously
      amplified using quantitative fluorescence PCR (QF PCR). Using this method, 60
      previously cytogenetically diagnosed DS with standard type of trisomy 21 were
      confirmed. Furthermore, six of eight children with mosaic type of DS were
      detected. Two false negative results for mosaic type of DS were obtained.
      Finally, five children with the translocation type of Down syndrome were also
      confirmed with this molecular test. In conclusion, molecular genetic analysis of
      STR loci is fast, cheap and simple method that could be used in detection of DS.
      Regarding possible false results detected for certain number of mosaic types,
      cytogenetic analysis should be used as a confirmatory test.

PMID- 24856380
TI  - Retrospective mutational analysis of NPHS1, NPHS2, WT1 and LAMB2 in children with
      steroid-resistant focal segmental glomerulosclerosis - a single-centre
      experience.
AB  - The aim of our study was to examine NPHS1, NPHS2, WT1 and LAMB2 mutations,
      previously reported in two thirds of patients with nephrotic syndrome with onset
      before the age of one year old. Genomic DNA samples from Polish children (n=33)
      with Steroid-Resistant Nephrotic Syndrome (SRNS) due to focal segmental
      glomerulosclerosis (FSGS), manifesting before the age of 13 years old, underwent
      retrospective analysis of NPHS1, NPHS2, WT1 (exons 8, 9 and adjacent exon/intron
      boundaries) and LAMB2. No pathogenic NPHS1 or LAMB2 mutations were found in our
      FSGS cohort. SRNS-causing mutations of NPHS2 and WT1 were detected in 7 of 33
      patients (21%), including those with nephrotic syndrome manifesting before one
      year old: five of seven patients. Four patients had homozygous c.413G>A
      (p.Arg138Gln) NPHS2 mutations; one subject was homozygous for c.868G>A
      (p.Val290Met) NPHS2. A phenotypic female had C>T transition at position +4 of the
      WT1 intron 9 (c.1432+4C>T) splice-donor site, and another phenotypic female was
      heterozygous for G>A transition at position +5 (c.1432+5G>A). Genotyping revealed
      a female genotypic gender (46, XX) for the first subject and male (46, XY) for
      the latter. In addition, one patient was heterozygous for c.104dup
      (p.Arg36Profs*34) NPHS2; two patients carried a c.686G>A (p.Arg229Gln) NPHS2 non
      neutral variant. Results indicate possible clustering of causative NPHS2
      mutations in FSGS-proven SRNS with onset before age one year old, and provide
      additional evidence that patients with childhood steroid-resistant nephrotic
      syndrome due to focal segmental glomerulosclerosis should first undergo analysis
      of NPHS2 coding sequence and WT1 exons 8 and 9 and surrounding exon/intron
      boundary sequences, followed by gender genotyping.

PMID- 24856382
TI  - Eucalyptus globulus extract protects upon acetaminophen-induced kidney damages in
      male rat.
AB  - Plants have historically been used in treating many diseases. Eucalyptus
      globules, a rich source of bioactive compounds, and have been shown to possess
      antioxidative properties. The purpose of this study, carried out on male Wistar
      rats, was to evaluate the beneficial effects of Eucalyptus globulus extract upon
      acetaminophen-induced damages in kidney. Our study is realized in the Department
      of Biology, Faculty of Sciences of Sfax (Tunisia). 32 Wistar male rats; were
      divided into 4 batches: a control group (n=8), a group of rats treated with
      acetaminophen (900 mg/kg) by intraperitoneal injection during 4 days (n=8), a
      group receiving Eucalyptus globulus extract (130 mg of dry leaves/kg/day) in
      drinking water during 42 days after 2 hours of acetaminophen administration
      (during 4 days) (n=8) and group received only Eucalyptus (n=8) during 42 days.
      After 6 weeks, animals from each group were rapidly sacrificed by decapitation.
      Blood serum was obtained by centrifugation. Under our experimental conditions,
      acetaminophen poisoning resulted in an oxidative stress evidenced by
      statistically significant losses in the activities of catalase (CAT), superoxide
      dismutase (SOD), glutathione-peroxidase (GPX) activities and an increase in
      lipids peroxidation level in renal tissue of acetaminophen-treated group compared
      with the control group. Acetaminophen also caused kidney damage as evident by
      statistically significant (p<0.05) increase in levels of creatinine and urea and
      decreased levels of uric acid and proteins in blood. Histological analysis
      demonstrated alteration of proximal tubules, atrophy of the glomerule and
      dilatation of urinary space. Previous administration of plant extract is found to
      alleviate this acetaminophen-induced damage.

PMID- 24856384
TI  - Clinical relevance of IL-6 gene polymorphism in severely injured patients.
AB  - In polytrauma, injuries that may be surgically treated under regular
      circumstances due to a systemic inflammatory response become life-threatening.
      The inflammatory response involves a complex pattern of humoral and cellular
      responses and the expression of related factors is thought to be governed by
      genetic variations. This aim of this paper is to examine the influence of
      interleukin (IL) 6 single nucleotide polymorphism (SNP) -174C/G and -596G/A on
      the treatment outcome in severely injured patients. Forty-seven severely injured
      patients were included in this study. Patients were assigned an Injury Severity
      Score. Blood samples were drawn within 24 h after admission (designated day 1)
      and on subsequent days (24, 48, 72 hours and 7 days) of hospitalization. The IL-6
      levels were determined through ELISA technique. Polymorphisms were analyzed by a
      method of Polymerase Chain Reaction-Restriction Fragment Length Polymorphism
      (PCR). Among subjects with different outcomes, no statistically relevant
      difference was found with regards to the gene IL-6 SNP-174G/C polymorphism. More
      than a half of subjects who died had the SNP-174G/C polymorphism, while this
      polymorphism was represented in a slightly lower number in survivors. The
      incidence of subjects without polymorphism and those with heterozygous and
      homozygous gene IL-6 SNP-596G/A polymorphism did not present statistically
      significant variations between survivors and those who died. The levels of IL-6
      over the observation period did not present any statistically relevant difference
      among subjects without the IL-6 SNP-174 or IL- 6 SNP -596 gene polymorphism and
      those who had either a heterozygous or a homozygous polymorphism.

PMID- 24856385
TI  - Characterization of a versatile arylesterase from Lactobacillus plantarum active
      on wine esters.
AB  - The gene lp_1002 from Lactobacillus plantarum WCFS1 encoding a putative
      lipase/esterase was cloned and overexpressed in Escherichia coli BL21(DE3). The
      purified Lp_1002 protein was biochemically characterized. Lp_1002 is an
      arylesterase which showed high hydrolytic activity on phenyl acetate. Although to
      a lesser extent, Lp_1002 also hydrolyzed most of the esters assayed including
      relevant wine aroma compounds. Importantly, Lp_1002 exhibited hydrolytic activity
      at winemaking conditions, although optimal catalytic activity is observed at 40 
      degrees C and pH 5-7. The effect of wine compounds on Lp_1002 activity was
      assayed. From the compounds assayed (ethanol, sodium metabisulfite, and malic,
      tartaric, lactic and citric acids), only malic acid slightly inhibited Lp_1002
      activity. Lp_1002 is the first arylesterase described in a wine lactic acid
      bacteria and possessed suitable biochemical properties to be used during
      winemaking. 

PMID- 24856383
TI  - Ameliorative effect of vanadium on oxidative stress in stomach tissue of diabetic
      rats.
AB  - Between their broad spectrum of action, vanadium compounds are shown to have
      insulin mimetic/enhancing effects. Increasing evidence in experimental and
      clinical studies suggests that oxidative stress plays a major role in the
      pathogenesis of diabetes and on the onset of diabetic complications. Thus,
      preventive therapy can alleviate the possible side effects of the disease. The
      aim of the present study was to investigate the effect of vanadyl sulfate
      supplementation on the antioxidant system in the stomach tissue of diabetic rats.
      Male Swiss albino rats were randomly divided into 4 groups: control;
      control+vanadyl sulfate; diabetic; diabetic+vanadyl sulfate. Diabetes was induced
      by intraperitoneal injection of streptozotocin (STZ; 65 mg/kg body weight).
      Vanadyl sulfate (100 mg/kg body weight) was given daily by gavage for 60 days. At
      the last day of the experiment, stomach tissues were taken and homogenized to
      make a 10% (w/v) homogenate. Catalase (CAT), superoxide dismutase (SOD),
      glutathione reductase (GR), glutathione peroxidase (GPx), glutathione-S
      transferase (GST), myeloperoxidase (MPO), carbonic anhydrase (CA), glucose-6
      phosphate dehydrogenase (G6PD) and lactate dehydrogenase (LDH) activities were
      determined in the stomach tissue. CAT, SOD, GR, GPx, GST, CA, G6PD and LDH
      activities were increased in diabetic rats when compared to normal rats. Vanadium
      treatment significantly reduced the elevated activities of GR, GPx, GST compared
      with the diabetic group whereas the decreases in CAT, SOD, CA, G6PD and LDH
      activities were insignificant. No significant change was seen for MPO activity
      between the groups. It was concluded that vanadium could be used for its
      ameliorative effect against oxidative stress in diabetes.

PMID- 24856386
TI  - Phenotypic mapping of metabolic profiles using self-organizing maps of high
      dimensional mass spectrometry data.
AB  - A metabolic system is composed of inherently interconnected metabolic precursors,
      intermediates, and products. The analysis of untargeted metabolomics data has
      conventionally been performed through the use of comparative statistics or
      multivariate statistical analysis-based approaches; however, each falls short in
      representing the related nature of metabolic perturbations. Herein, we describe a
      complementary method for the analysis of large metabolite inventories using a
      data-driven approach based upon a self-organizing map algorithm. This workflow
      allows for the unsupervised clustering, and subsequent prioritization of,
      correlated features through Gestalt comparisons of metabolic heat maps. We
      describe this methodology in detail, including a comparison to conventional
      metabolomics approaches, and demonstrate the application of this method to the
      analysis of the metabolic repercussions of prolonged cocaine exposure in rat sera
      profiles. 

PMID- 24856392
TI  - Nurses as boundary-spanners in reducing avoidable hospitalizations among nursing
      home residents.
AB  - An increasing number of nursing home quality improvement efforts are aimed at
      reducing avoidable hospitalizations of residents. The current study focused on
      the experiences of nursing home nurses as "boundary-spanners" in the
      implementation of initiatives aimed at this effort. In-depth, semi-structured
      interviews were conducted with 76 nursing staff members within 38 nursing homes.
      Data were analyzed using thematic analysis and an inductive category development
      approach. Nursing staff described multiple scenarios where they had acted to
      negotiate the hospitalization decision and described themselves as working both
      within the nursing home boundary and within the larger system of external
      stakeholders to avoid a hospital transfer. There is potential for role overload
      and strain, as nurses are required to provide for complex medical needs within
      facilities designed to encourage relationship-driven, home-like care. Future
      efforts to reduce avoidable hospitalizations may benefit by ensuring needed
      resources are in place to provide clinically complex care and by making efforts
      to reduce the challenges that emerge when nurses are in the position to span the
      boundary between the nursing home and outside stakeholders.

PMID- 24856395
TI  - A comparative investigation of modern feature selection and classification
      approaches for the analysis of mass spectrometry data.
AB  - Many analytical approaches such as mass spectrometry generate large amounts of
      data (input variables) per sample analysed, and not all of these variables are
      important or related to the target output of interest. The selection of a smaller
      number of variables prior to sample classification is a widespread task in many
      research studies, where attempts are made to seek the lowest possible set of
      variables that are still able to achieve a high level of prediction accuracy; in
      other words, there is a need to generate the most parsimonious solution when the
      number of input variables is huge but the number of samples/objects are smaller.
      Here, we compare several different variable selection approaches in order to
      ascertain which of these are ideally suited to achieve this goal. All variable
      selection approaches were applied to the analysis of a common set of metabolomics
      data generated by Curie-point pyrolysis mass spectrometry (Py-MS), where the goal
      of the study was to classify the Gram-positive bacteria Bacillus. These
      approaches include stepwise forward variable selection, used for linear
      discriminant analysis (LDA); variable importance for projection (VIP)
      coefficient, employed in partial least squares-discriminant analysis (PLS-DA);
      support vector machines-recursive feature elimination (SVM-RFE); as well as the
      mean decrease in accuracy and mean decrease in Gini, provided by random forests
      (RF). Finally, a double cross-validation procedure was applied to minimize the
      consequence of overfitting. The results revealed that RF with its variable
      selection techniques and SVM combined with SVM-RFE as a variable selection
      method, displayed the best results in comparison to other approaches. 

PMID- 24856396
TI  - DNA-based hybridization chain reaction amplification for assaying the effect of
      environmental phenolic hormone on DNA methyltransferase activity.
AB  - In this work, a novel electrochemical protocol with signal amplification for
      determination of DNA methylation and methyltransferase activity using DNA-based
      hybridization chain reaction (HCR) was proposed. After the gold electrode was
      modified with dsDNA, it was treated with M.SssI MTase, HpaII endonuclease,
      respectively. And then the HCR was initiated by the target DNA and two hairpin
      helper DNAs, which lead to the formation of extended dsDNA polymers on the
      electrode surface. The signal was amplified by the labeled biotin on the hairpin
      probes. As a result, the streptavidin-alkaline phosphatase (S-ALP) conjugated on
      the electrode surface through the specific interaction between biotin and S-ALP.
      ALP could convert 1-naphthyl phosphate into 1-naphthol and the latter could be
      electrochemically oxidized, which was used to monitor the methylation event and
      MTase activity. The HCR assay presents good electrochemical responses for the
      determination of M.SssI MTase at a concentration as low as 0.0067 uni tmL(-1).
      Moreover, the effects of anti-cancer drug and environmental phenolic hormone on
      M.SssI MTase activity were also investigated. The results indicated that 5
      fluorouracil and daunorubicin hydrochloride could inhibit the activity, and the
      opposite results were obtained with bisphenol A and nonylphenol. Therefore, this
      method can not only provide a platform to screen the inhibitors of DNA MTase and
      develop new anticancer drugs, but also offer a novel technique to investigate the
      possible carcinogenesis mechanism.

PMID- 24856397
TI  - Prussian blue-gold nanoparticles-ionic liquid functionalized reduced graphene
      oxide nanocomposite as label for ultrasensitive electrochemical immunoassay of
      alpha-fetoprotein.
AB  - In this work, poly(diallyldimethylammonium chloride) (PDDA) protected Prussian
      blue/gold nanoparticles/ionic liquid functionalized reduced graphene oxide (IL
      rGO-Au-PDDA-PB) nanocomposite was fabricated. The resulting nanocomposite
      exhibited high biocompatibility, conductivity and catalytic activity. To assess
      the performance of the nanocomposite, a sensitive sandwich-type immunosensor was
      constructed for detecting alpha-fetoprotein (AFP). Greatly enhanced sensitivity
      for this immunosensor was based on triple signal amplification strategies.
      Firstly, IL-rGO modified electrode was used as biosensor platform to capture a
      large amount of antibody due to its increased surface area, thus amplifying the
      detection response. Secondly, a large number of Au-PDDA-PB was conjugated on the
      surface of IL-rGO, which meant the enrichment of the signal and the more
      immobilization of label antibody. Finally, the catalytic reaction between H2O2
      and the IL-rGO-Au-PDDA-PB nanocomposite further enhanced the signal response. The
      signals increased linearly with AFP concentrations in the range of 0.01-100 ng
      mL(-1). The detection limit for AFP was 4.6 pg mL(-1). The immunosensor showed
      high sensitivity, excellent selectivity and good stability. Moreover, the
      immunosensor was applied to the analysis of AFP in serum sample with satisfactory
      result.

PMID- 24856398
TI  - In situ growth of IRMOF-3 combined with ionic liquids to prepare solid-phase
      microextraction fibers.
AB  - A superior solid-phase microextraction (SPME) fiber-coating material, IRMOF
      3@ILs/PDMS, was prepared by the in situ growth of IRMOF-3 onto stainless-steel
      wires and protection with ionic liquids (ILs) and polydimethylsiloxane (PDMS).
      The ILs can efficiently prevent the substantial cracking of IRMOF-3 caused by
      moisture, and a thin PDMS film can protect the IRMOF-3@ILs material to achieve a
      much better extraction efficiency as well as excellent resistance to high
      temperature and high humidity. This IRMOF-3@ILs/PDMS coating possessed a porous
      structure, a rough surface and an increased lifespan (by at least 100 times)
      compared with that of IRMOF-3. The coating was evaluated by analyzing four
      polycyclic aromatic hydrocarbons (PAHs) in water, and good precision (<7.7%), low
      detection limits (12.0-15.4 ng L(-1)), and wide linearity (50-20,000 ng L(-1))
      were achieved under the optimized conditions. The fiber was successfully applied
      to the sensitive analysis of PAHs in rainwater by coupling it with gas
      chromatography-mass spectrometry (GC-MS).

PMID- 24856391
TI  - Ocular cytochrome P450s and transporters: roles in disease and endobiotic and
      xenobiotic disposition.
AB  - Drug metabolism and transport processes in the liver, intestine and kidney that
      affect the pharmacokinetics and pharmacodynamics of therapeutic agents have been
      studied extensively. In contrast, comparatively little research has been
      conducted on these topics as they pertain to the eye. Recently, however,
      catalytic functions of ocular cytochrome P450 enzymes have gained increasing
      attention, in large part due to the roles of CYP1B1 and CYP4V2 variants in
      primary congenital glaucoma and Bietti's corneoretinal crystalline dystrophy,
      respectively. In this review, we discuss challenges to ophthalmic drug delivery,
      including Phase I drug metabolism and transport in the eye, and the role of three
      specific P450s, CYP4B1, CYP1B1 and CYP4V2 in ocular inflammation and genetically
      determined ocular disease.

PMID- 24856399
TI  - Liquid-liquid microextraction in a multicommuted flow system for direct
      spectrophotometric determination of iodine value in biodiesel.
AB  - A flow-based procedure was developed for the direct spectrophotometric
      determination of the iodine value (IV) in biodiesel. The procedure was based on
      the microextraction/reaction of unsaturated compounds with triiodide ions in an
      aqueous medium by inserting the reagent solution between the aliquots of
      biodiesel without any pretreatment. The interaction occurred through the
      biodiesel film formed on the inner walls of the hydrophobic tube used as the
      reactor and at the aqueous/biodiesel interfaces. The spectrophotometric detection
      was based on the discoloration of the I3(-) reagent in the aqueous phase by using
      a glass tube coupled to a fiber-optic spectrophotometer as the detection cell.
      Reference solutions were prepared by dilution of biodiesel samples with
      previously determined IV in hexane. The analytical response was linear for IV
      from 13 to 135 g I2/100 g with a detection limit of 5 g I2/100 g. A coefficient
      of variation of 1.7% (n=10) and a sampling rate of 108 determinations per hour
      were achieved by consuming 224 MUL of the sample and 200 MUg of I2 per
      determination. The slopes of analytical curves obtained with three different
      biodiesel samples were in agreement (variations in slopes lower than 3.1%), thus
      indicating an absence of any matrix effects. Results for biodiesel samples from
      different sources agreed with the volumetric official procedure at the 95%
      confidence level. The proposed procedure is therefore a simple, fast, and
      reliable alternative for estimating the iodine value of biodiesel.

PMID- 24856400
TI  - Determination of bovine lactoferrin in dairy products by ultra-high performance
      liquid chromatography-tandem mass spectrometry based on tryptic signature
      peptides employing an isotope-labeled winged peptide as internal standard.
AB  - A new and sensitive determination method was developed for bovine lactoferrin in
      dairy products including infant formulas based on the signature peptide by ultra
      high-performance liquid chromatography and triple-quadrupole tandem mass
      spectrometry under the multiple reaction monitoring mode. The simple pretreatment
      procedures included the addition of a winged peptide containing the isotope
      labeled signature peptide as internal standard, followed by an enzymatic
      digestion with trypsin. The signature peptide was chosen and identified from the
      tryptic hydrolyzates of bovine lactoferrin by ultra high-performance liquid
      chromatography and quadrupole-time-of-flight tandem mass spectrometry based on
      sequence database search. Analytes were separated on an ACQUITY UPLC BEH 300 C18
      column and monitored by MS/MS in seven minutes. Quantitative result bias due to
      matrix effect and tryptic efficiency was corrected through the use of synthetic
      isotope-labeled standards. The limit of detection and limit of quantification
      were 0.3 mg/100 g and 1.0 mg/100 g, respectively. Bovine lactoferrin within the
      concentration range of 10-1000 nmol L(-1) showed a strong linear relationship
      with a linear correlation coefficient (r) of >0.998. The intra- and inter-day
      precision of the method were RSD<6.5% and RSD<7.1%, respectively. Excellent
      repeatability (RSD<6.4%) substantially supported the application of this method
      for the determination of bovine lactoferrin in dairy samples. The present method
      was successfully validated and applied to determination of bovine lactoferrin in
      dairy products including infant formulas.

PMID- 24856401
TI  - Analysis of the human urine endogenous peptides by nanoparticle extraction and
      mass spectrometry identification.
AB  - Peptides in urine are excreted by kidney from the blood and tissues, which are
      composed of a large amount of hormones, cytokines, regulatory factors and the
      metabolized fragments of proteins. The peptide distribution in urine will reflect
      the physiological and pathophysiological processes in body. In past, limited
      information was reported about the composition of the peptides in urine. One
      possible reason is that the peptides in urine are fairly low abundant and there
      are high concentrations of salts and organic metabolites in the urine. In this
      report, we extracted the peptides from human urine by highly ordered mesoporous
      silica particles with the pore size of 2 nm, which will exclude the high
      molecular weight proteins over 12 kDa. The extracted peptides were then separated
      into fractions according to their molecular weight by size exclusion
      chromatography. Each of the fractions was further analyzed by MALDI-TOF MS and
      MURPLC-MS/MS. Totally, 193 peptides were identified by two-dimensional SEC/MURPLC
      MS/MS analysis. By analyzing the progenitor protein of the peptides; we found
      that two-thirds of the proteins differed from the reported urine proteome
      database, and the high abundant proteins in urine proteome were less detected in
      the urine peptidome. The developed extraction and separation methods were
      efficient for the profiling of the endogenous peptides in human urine. The
      peptidome in human urine was complementary to the human urinary proteome and may
      provide an emerging field for biomarker discovery.

PMID- 24856402
TI  - Fast functionalization of silver decahedral nanoparticles with aptamers for
      colorimetric detection of human platelet-derived growth factor-BB.
AB  - Aptamer-silver decahedral nanoparticles (Ag10NPs-aptamer) based detection was
      developed for protein. Ag10NPs were synthesized by photochemical method. The
      advantage of Ag10NPs was its tolerance of NaCl which facilitates the
      functionalization of silver nanoparticles with all kinds of ssDNA. Attaching
      aptamers to Ag10NPs could be achieved within 2 h, much faster than traditional
      methods. Human platelet-derived growth factor-BB (PDGF-BB) was used as a model
      protein to test the binding capacity of aptamers attached on Ag10NPs. Our data
      showed that the aptamer-Ag10NPs conjugates were successful in detecting human
      PDGF-BB. Furthermore, we developed an aptamer-Ag10NPs conjugates-based
      colorimetric sensor to detect PDGF-BB. The results showed a linear relationship
      between PDGF-BB concentrations (5 ng mL(-1)-200 ng mL(-1)) and DeltaOD with
      excellent detection specificity in serum. Therefore, the sensor based on aptamer
      Ag10NPs conjugates was highly effective and sensitive and had great promise for
      further development and applications.

PMID- 24856403
TI  - A ratiometric fluorescent chemosensor for Al3+ in aqueous solution based on
      aggregation-induced emission and its application in live-cell imaging.
AB  - A ratiometric fluorescent chemosensor 1 was developed for the detection of Al(3+)
      in aqueous solution based on aggregation-induced emmision (AIE). The chemosensor
      showed the fluorescence of its aggregated state and Al(3+)-chelated soluble state
      in the absence and in the presence of Al(3+), respectively, and resulted in a
      fluorescence ratio (I461/I537) response to Al(3+) in neutral aqueous solution at
      a detection limit as low as 0.29 MUmol L(-1). The method was also highly
      selective to Al(3+) over other physiological relevant metal ions investigated in
      this study. Taking advantage of its AIE characteristics, the chemosensor was
      successfully applied on test papers for simple and rapid detection of Al(3+).
      Moreover, the application of 1 for the imaging of Al(3+) in living cells by
      ratiometric fluorescence changes was also achieved.

PMID- 24856404
TI  - Selective and sensitive homogenous assay of serum albumin with 1
      anilinonaphthalene-8-sulphonate as a biosensor.
AB  - Homogenous selective assay of albumin (ALB) in clinical sera was tested with 1
      anilinonaphthalene-8-sulphonate (ANS) as Forster-resonance-energy-transfer (FRET)
      acceptor of tryptophan residues and biosensor of ALB. Between the excitation at
      280 and 350 nm, the ratio of the fluorescence at 470 nm of free ANS in ethanol
      was about 1.9 while that of the complexes of ALB and ANS was about 3.9,
      supporting FRET in complexes of ANS and ALB. ANS below 1.0 mM saturated one site
      of ALB with Kd of about 0.13 MUM in 20 mM sodium phosphate buffer at pH 7.0. For
      selective assay of ALB, 0.30 MUM ANS was used to quantify fluorescence of the
      complexes at 470 nm under the excitation at 280 nm. ALB from 1.8 to 25 nM was
      quantified, whose lower limit was below 1% than that by bromocresol green assay
      while one-third than that by immunoturbidimetric assay. Globular proteins at
      comparable levels gave negligible signals. This new method showed reasonable
      resistance to other interfering substances in clinical sera. Quantities of ALB in
      clinical sera by this method were consistent with those by bromocresol green
      assay and immunoturbidimetric assay. Hence, homogenous assay of ALB with ANS as
      FRET biosensor was effective.

PMID- 24856405
TI  - Aflatoxin B1 and M1 in milk.
AB  - The aflatoxin M1 (AFLAM1) is a mycotoxin that results from the hydroxylation of
      the aflatoxin B1 (AFLAB1). It contaminates the milk of animals fed with a diet
      containing its precursor. In this work, we determined the occurrence of AFLAB1
      and AFLAM1 in milk, as well as the chromatographic conditions to quantify these
      mycotoxins. The extraction and quantification of AFLAB1 and AFLAM1 in naturally
      contaminated and artificially spiked milk samples which are produced and marketed
      in the state of RS were performed using the AOAC official method and UHPLC with
      fluorescence detection. We obtained a separation factor of 2.3 for AFLAB1 and
      AFLAM1 using a mobile phase consisting of 1% acetic acid:acetonitrile:methanol
      (55:10:35). The analytical curves had a wide linearity range and the limit of
      quantification (LOQm) concentrations of AFLAB1 and AFLAM1 were equal to 0.5 and
      0.25 MUg L(-1), respectively. Samples of pasteurized and ultra-high-temperature
      processed (UHT) milk showed natural contamination, and the levels for both
      aflatoxins ranged from 0.7 to 1.5 MUg L(-1). Raw and concentrated milk samples
      only contained AFLAM1, with a maximum average concentration of 1.7 MUg L(-1).
      These concentrations, higher than permitted by legislation, confirm the existence
      of a health risk, as well as highlight the relevance of searching for
      alternatives to reduce this contamination.

PMID- 24856406
TI  - Americium and plutonium separation by extraction chromatography for determination
      by accelerator mass spectrometry.
AB  - A simple method was developed to separate Pu and Am using single column
      extraction chromatography employing N,N,N',N'-tetra-n-octyldiglycolamide (DGA)
      resin. Isotope dilution measurements of Am and Pu were performed using
      accelerator mass spectrometry (AMS) and alpha spectrometry. For maximum
      adsorption Pu was stabilized in the tetra valent oxidation state in 8M HNO3 with
      0.05 M NaNO2 before loading the sample onto the resin. Am(III) was adsorbed also
      onto the resin from concentrated HNO3, and desorbed with 0.1 M HCl while keeping
      the Pu adsorbed. The on-column reduction of Pu(IV) to Pu(III) with 0.02 M TiCl3
      facilitated the complete desorption of Pu. Interferences (e.g. Ca(2+), Fe(3+))
      were washed off from the resin bed with excess HNO3. Using NdF3, micro
      precipitates of the separated isotopes were prepared for analysis by both AMS and
      alpha spectrometry. The recovery was 97.7+/-5.3% and 95.5+/-4.6% for (241)Am and
      (242)Pu respectively in reagents without a matrix. The recoveries of the same
      isotopes were 99.1+/-6.0 and 96.8+/-5.3% respectively in garden soil. The
      robustness of the method was validated using certified reference materials (IAEA
      384 and IAEA 385). The measurements agree with the certified values over a range
      of about 1-100 Bq kg(-1). The single column separation of Pu and Am saves
      reagents, separation time, and cost.

PMID- 24856407
TI  - Persistent cystic fibrosis isolate Pseudomonas aeruginosa strain RP73 exhibits an
      under-acylated LPS structure responsible of its low inflammatory activity.
AB  - Pseudomonas aeruginosa, the major pathogen involved in lethal infections in
      cystic fibrosis (CF) population, is able to cause permanent chronic infections
      that can persist over the years. This ability to chronic colonize CF airways is
      related to a series of adaptive bacterial changes involving the immunostimulant
      lipopolysaccharide (LPS) molecule. The structure of LPSs isolated from several P.
      aeruginosa strains showed conserved features that can undergo chemical changes
      during the establishment of the chronic infection. In the present paper, we
      report the elucidation of the structure and the biological activity of the R-LPS
      (lipooligosaccharide, LOS) isolated from the persistent CF isolate P. aeruginosa
      strain RP73, in order to give further insights in the adaptation mechanism of the
      pathogen in the CF environment. The complete structural analysis of P. aeruginosa
      RP73 LOS was achieved by chemical analyses, NMR spectroscopy and MALDI MS
      spectrometry, while the assessment of the biological activity was attained
      testing the in vivo pro-inflammatory capacity of the isolated LOS molecule. While
      a typical CF LPS is able to trigger a high immune response and production of pro
      inflammatory molecules, this P. aeruginosa RP73 LOS showed to possess a low pro
      inflammatory capacity. This was possible due to a singular chemical structure
      possessing an under-acylated lipid A very similar to the LPS of P. aeruginosa
      found in chronic lung diseases such as bronchiectstasis. 

PMID- 24856408
TI  - Early socioeconomic adversity and young adult physical illness: the role of body
      mass index and depressive symptoms.
AB  - PURPOSE: The present study investigated the psychophysiological inter- and intra
      individual processes that mediate the linkage between childhood and/or adolescent
      socioeconomic adversities and adult health outcomes. Specifically, the proposed
      model examined the roles of youth depressive symptoms and body mass index (BMI)
      trajectories as mediators that explain the link between early adversity and young
      adults' general health and physical illnesses after controlling for gender, race
      or ethnicity, and earlier general health reports. METHODS: Using a nationally
      representative sample of 12,424 from National Longitudinal Study of Adolescent
      Health (Add Health), this study used growth curve modeling to consider both the
      severity (initial level) and the change over time (deterioration or elevation) as
      psychophysiological mediators, thereby acknowledging multiple facets of
      depressive symptoms and BMI trajectories as psychophysiological mediators of
      early adversity to adult health. RESULTS: Results provide evidence for (1) the
      influence of early childhood and early adolescent cumulative socioeconomic
      adversity on both the initial levels and changes over time of depressive symptoms
      and BMI and (2) the independent influences depressive symptoms and BMI
      trajectories on the general health and the physical illnesses of young adults.
      CONCLUSIONS: These findings contribute valuable knowledge to existing research by
      elucidating how early adversity exerts an enduring long-term influence on
      physical health problems in young adulthood; furthermore, this information
      suggests that effective intervention and prevention programs should incorporate
      multiple facets (severity and change over time) of multiple mechanisms
      (psychological and physiological).

PMID- 24856409
TI  - Association between nonmedical prescription drug use and health status among
      young Swiss men.
AB  - PURPOSE: To examine the relationship between the nonmedical prescription drug use
      (NMPDU) of six drug classes and health. METHODS: Data on young adults males (mean
      age, 19.96 years) from the baseline and follow-up of the Cohort Study on
      Substance Use Risk Factors (C-SURF) were used (n = 4,958). Two sets of logistic
      regression models were fitted to examine the associations between NMPDU of opioid
      analgesics, sedatives or sleeping pills, anxiolytics, antidepressants, beta
      blockers and stimulants, and health status (assessed using the Medical Outcomes
      Study 12-Item Short Form Survey Instrument [SF-12 v2]). We first computed odds
      ratios between NMPDU at baseline and poor mental and physical health at follow
      up, adjusting for poor mental or physical health at baseline. We then computed
      odds ratios between poor mental and physical health at baseline and NMPDU at
      follow-up, adjusting for NMPDU at baseline. RESULTS: Three key findings regarding
      mental health were (1) there was a reciprocal risk between poor mental health and
      sedatives and anxiolytics; (2) poor mental health increased NMPDU of opioid
      analgesics and antidepressants but not vice versa; and (3) there were no
      associations with stimulants. Three key findings regarding physical health were
      (1) poor physical health increased the risk of NMPDU of anxiolytics; (2) the only
      reciprocal risk was between physical health and NMPDU of opioid analgesics; and
      (3) there were no associations with stimulants. CONCLUSION: These results, among
      the first ever on reciprocal effects between NMPDU and mental and physical health
      status, give unique information concerning the adverse effects of NMPDU on health
      and vice versa. The study shows that NMPDU is not only a sign of self-medication
      but may induce health problems.

PMID- 24856410
TI  - Synthesis and biological evaluation of novel bisbenzimidazoles as Escherichia
      coli topoisomerase IA inhibitors and potential antibacterial agents.
AB  - Novel bisbenzimidazole inhibitors of bacterial type IA topoisomerase are of
      interest for the development of new antibacterial agents that are impacted by
      target-mediated cross resistance with fluoroquinolones. The present study
      demonstrates the successful synthesis and evaluation of bisbenzimidazole
      analogues as Escherichia coli topoisomerase IA inhibitors. 5-(4-Propylpiperazin-1
      yl)-2-[2'-(4-ethoxyphenyl)-5'-benzimidazolyl]benzimidazole (12b) showed
      significant relaxation inhibition activity against EcTopo 1A (IC50 = 2 +/- 0.005
      MUM) and a tendency to chelate metal ion. Interestingly, these compounds did not
      show significant inhibition of E. coli DNA gyrase and hTop 1 even up to 100 MUM.
      Compound 12b has shown lowest MIC against E. coli strains among 24 compounds
      evaluated. The binding affinity constant and binding free energy of 12b with
      EcTopo 1A was observed 6.8 * 10(6) M(-1) and -10.84 kcal mol(-1) from isothermal
      titration calorimetry (ITC), respectively. In vivo mouse systemic infection and
      neutropenic thigh model experimental results confirmed the therapeutic efficacy
      of 12b, suggesting further development of this class of compounds as
      antibacterial agents.

PMID- 24856411
TI  - ZnO-supported Pd nanoparticle-catalyzed ligand- and additive-free cyanation of
      unactivated aryl halides using K4[Fe(CN)6].
AB  - The use of a new ZnO-supported palladium(0) nanoparticle catalyst for the
      cyanation of aryl halides using a relatively benign cyanide source, K4[Fe(CN)6],
      is described. This catalyst has been applied for the efficient cyanation of a
      variety of functionalized aryl bromides and activated aryl chlorides. This
      process circumvents the need for an additive and a ligand for the reaction and
      offers the advantages of high product yields, low catalyst loading (0.2 mol %
      Pd), and recyclability of the catalyst. 

PMID- 24856412
TI  - Perceived discrimination and psychotic experiences across multiple ethnic groups
      in the United States.
AB  - OBJECTIVE: The objective of this study was to examine the relationship between
      perceived discrimination and psychotic experiences (PE) using validated measures
      of discrimination and a racially/ethnically diverse population-level sample.
      METHODS: Data were drawn from two population-level surveys (The National Latino
      and Asian American Survey and The National Survey of American Life), which were
      analyzed together using survey weights and stratification variables. The analytic
      sample (N=8990) consisted of Latino, Asian, African-American, and Afro-Caribbean
      adults living in the United States. Separate unadjusted and adjusted
      multivariable logistic regression models were used, first to examine the crude
      bivariate relationship between perceived discrimination and PE, and second to
      examine the relationship adjusting for demographic variables. Adjusted logistic
      regression models were also used to examine the relationships between perceived
      discrimination and specific sub-types of PE (auditory and visual hallucinatory
      experiences, and delusional ideation). RESULTS: When compared to individuals who
      did not report any discrimination, those who reported the highest levels of
      discrimination were significantly more likely to report both 12-month PE
      (Adjusted OR=4.590, p<0.001) and lifetime PE (adjusted OR=4.270, p<0.001). This
      held true for visual hallucinatory experiences (adjusted OR=3.745, p<0.001),
      auditory hallucinatory experiences (adjusted OR=5.649, p<0.001), and delusional
      ideation (adjusted OR=7.208, p<0.001). CONCLUSION: Perceived discrimination is
      associated with the increased probability of reporting psychotic experiences in a
      linear Fashion in the US general population.

PMID- 24856418
TI  - Diminution of contact angle hysteresis under the influence of an oscillating
      force.
AB  - We suggest a simple quantitative model for the diminution of contact angle
      hysteresis under the influence of an oscillatory force invoked by thermal
      fluctuations, substrate vibrations, acoustic waves, or oscillating electric
      fields. Employing force balance rather than the usual description of contact
      angle hysteresis in terms of Gibbs energy, we highlight that a wetting system,
      such as a sessile drop or a bubble adhered to a solid substrate, appears at long
      times to be partially or fully independent of contact angle hysteresis and thus
      independent of static friction forces, as a result of contact line pinning. We
      verify this theory by studying several well-known experimental observations such
      as the approach of an arbitrary contact angle toward the Young contact angle and
      the apparent decrease (or increase) in an advancing (or a receding) contact angle
      under the influence of an external oscillating force. 

PMID- 24856417
TI  - Rapid spread and diversification of respiratory syncytial virus genotype ON1,
      Kenya.
AB  - Respiratory syncytial virus genotype ON1, which is characterized by a 72-nt
      duplication in the attachment protein gene, has been detected in >10 countries
      since first identified in Ontario, Canada, in 2010. We describe 2 waves of
      genotype ON1 infections among children admitted to a rural hospital in Kenya
      during 2012. Phylogenetic analysis of attachment protein gene sequences showed
      multiple introductions of genotype ON1; variants distinct from the original
      Canadian viruses predominated in both infection waves. The genotype ON1 dominated
      over the other group A genotypes during the second wave, and some first wave ON1
      variants reappeared in the second wave. An analysis of global genotype ON1
      sequences determined that this genotype has become considerably diversified and
      has acquired signature coding mutations within immunogenic regions, and its most
      recent common ancestor dates to ~2008-2009. Surveillance of genotype ON1
      contributes to an understanding of the mechanisms of rapid emergence of
      respiratory viruses. 

PMID- 24856419
TI  - Antibiotic susceptibility pattern and erythromycin resistance mechanisms in beta
      hemolytic group G Streptococcus dysgalactiae subspecies equisimilis isolates from
      central Taiwan.
AB  - BACKGROUND/PURPOSE: Information concerning antibiotics susceptibilities of beta
      hemolytic group G Streptococcus dysgalactiae subspecies equisimilis (SDSE)
      clinical isolates in central Taiwan was limited. METHODS: Totally, 246 SDSE
      isolates were collected from mainly five regional hospitals, from February 2007
      to August 2011. Disk diffusion method, broth microdilution method, and
      clindamycin induction test (D test) were respectively performed according to the
      guidelines of the Clinical and Laboratory Standards Institute. Polymerase chain
      reaction was used to detect the corresponding erythromycin resistance genes.
      RESULTS: All isolates were susceptible to penicillin, cefotaxime, and vancomycin.
      The rate of erythromycin resistance was 24.0% (59/246), whereas that of
      clindamycin resistance was 12.2% (30/246). The resistance rates of isolates from
      different hospitals varied from 15.0% to 45.5% for erythromycin and from 7.1% to
      36.4% for clindamycin. For erythromycin-resistant SDSE isolates, three different
      phenotypes with resistance to macrolides (M), lincosamides (L), and type B
      streptogramins (SB) were observed: M (49.2%), constitutive MLSB (cMLSB, 35.6%),
      and inducible MLSB (iMLSB, 15.3%). All M phenotypic isolates carried mefA. The
      most prevalent genotypes among cMLSB and iMLSB phenotypic isolates were ermB,
      followed by ermTR. One isolate with cMLSB phenotype carried both ermB and ermTR,
      whereas one isolate with iMLSB phenotype carried both ermB and ermC. CONCLUSION:
      This is the first trial investigating the antimicrobial susceptibility pattern
      and erythromycin resistance mechanisms of beta-hemolytic group G SDSE isolates in
      central Taiwan. The resistance rates for both erythromycin and clindamycin varied
      significantly among hospitals located in this area and should be monitored
      continuously in the future.

PMID- 24856420
TI  - Impact of tumor necrosis factor receptor p55 deficiency in susceptibility of
      C57BL/6 mice to infection with Leishmania (Leishmania) amazonensis.
AB  - Tumor necrosis factor (TNF) is involved in host resistance to several
      intracellular pathogens. Although the critical role of TNF receptor (TNFR)p55 in
      Leishmania (Leishmania) major infection has been demonstrated, the impact of
      TNFRp55 deficiency on L. (L.) amazonensis infection has not been explored. L.
      (L.) amazonensis-infected TNFRp55(-/-) mice failed to resolve lesions, whereas
      C57BL/6 wild-type mice completely healed. The susceptibility of the TNFRp55(-/-)
      mice was characterized by higher lesion size and histopathological damage in
      comparison with the wild-type mice. A marked increased of the splenic index was
      observed in the TNFRp55(-/-) mice after 15 weeks infection. These results show
      that in the absence of TNFRp55, L. (L.) amazonensis-infected knockout mice fail
      to resolve lesions, whereas wild-type mice completely heal.

PMID- 24856421
TI  - Identification, epidemiological relatedness, and biofilm formation of clinical
      Chryseobacterium indologenes isolates from central Taiwan.
AB  - BACKGROUND: The clinical impact of Chryseobacterium indologenes infection is
      increasing; nevertheless, most studies had been conducted in northern Taiwan, but
      rarely in central Taiwan. METHODS: Using 16S rRNA gene sequencing, 34 isolates of
      C. indologenes were identified at the Central Region Hospital Alliance between
      2007 and 2011. Vitek 2 and matrix-assisted laser desorption ionization-time-of
      flight mass spectrometry (MALDI-TOF MS) methods were compared for the feasibility
      to identify this bacterium. Drug susceptibility test, biofilm formation, and
      pulsed-field gel electrophoresis (PFGE) were also performed. RESULTS: All
      isolates were collected from hospitalized patients with an average age of 70.8 +/
      18.5 years. The most prevalent sample was urine (50.0%), followed by sputum
      (32.4%). The accuracy rate of species-level identification reached 94.1% using
      the Vitek 2 method and 85.3% using the MALDI-TOF MS method. All of the isolates
      were resistant to gentamicin, amikacin, ceftriaxone, chloramphenicol, colistin,
      and imipenem, but completely susceptible to minocycline. While analyzing biofilm
      forming ability, 38.2% (13/34) of C. indologenes isolates displayed a positive
      phenotype using the Luria-Bertani (LB) medium. However, 80.0% (4/5) of invasive
      isolates were biofilm producers. Based on PFGE analysis, several clusters were
      found, and the possible intrahospital spread of this bacterium in this area could
      not be excluded. CONCLUSION: Both Vitek 2 and MALDI-TOF MS methods showed good
      ability in the determination of C. indologenes. Among the examined drugs,
      minocycline was the most potent one. As many as 38.2% C. indologenes isolates
      showed biofilm-forming ability. PFGE analyses revealed the possible intrahospital
      transmission of this bacterium in central Taiwan.

PMID- 24856422
TI  - In vitro interactions between fluconazole and minocycline against mixed cultures
      of Candida albicans and Staphylococcus aureus.
AB  - BACKGROUND/PURPOSE: It is difficult to manage coinfections in critically ill
      patients, especially in the presence of mixed-species biofilms. The aim of this
      study was to seek an effective drug combination for managing the dual-species
      biofilm of Candida albicans and Staphylococcus aureus. METHODS: The interaction
      between fluconazole and minocycline against polymicrobial planktonic cells and
      polymicrobial biofilms formed over four different time intervals (4 hours, 8
      hours, 12 hours, and 24 hours) was investigated using a microdilution
      checkerboard method. To explore whether the combined effects against the
      polymicrobial cultures involved calcium regulation, the effects of benidipine and
      ethylene glycol tetraacetic acid were characterized using a plate streaking
      method and a liquid-based quantitative method. RESULTS: Fluconazole combined with
      minocycline exerted strong effects against polymicrobial planktonic cells and
      polymicrobial biofilms formed over 4 hours, 8 hours, and 12 hours. The addition
      of benidipine and ethylene glycol tetraacetic acid enhanced the activity of the
      drug combination, suggesting that the combined effects may involve the
      perturbation of calcium homeostasis. CONCLUSION: Fluconazole in combination with
      minocycline is a potential approach for counteracting C. albicans-S. aureus dual
      species biofilms.

PMID- 24856423
TI  - Microbacterium spp. as a cause of peritoneal-dialysis-related peritonitis in two
      patients.

PMID- 24856424
TI  - Effects of chemical and low-temperature treatments and adaption on the responses
      of virulence factor genes and outer membrane proteins in Escherichia coli
      O157:H7.
AB  - BACKGROUND: In the years after the discovery of this pathogen, Escherichia coli
      O157:H7 has become increasingly prominent, and outbreaks have been reported in
      many areas. METHODS: In the current study, we determined the expressions of
      virulent factor genes shiga-like toxin II (stxII) and E. coli attaching and
      effacing (eaeA), in strains that were isolated from cattle feces and a clinical
      case in Taiwan. In addition, the effects of chemical and low-temperature stresses
      and adaptions on the expressions of virulent factor genes were investigated.
      Furthermore, the outer membrane proteins of acid-adapted E. coli O157:H7 TWC01
      (TWC01) was separated using two-dimensional electrophoresis, and proteins were
      identified using mass spectrometry in order to illustrate the changes in protein
      expression after adaption. RESULTS: Expressions of stxII and eaeA in the TWC01
      isolated from a clinical case were higher than those in two strains isolated from
      cattle feces, and both organic and inorganic acid stresses and adaptions enhance
      the expression of genes encoding virulent factors in strains. In addition, the
      outer membrane proteins of TWC01 were regulated under hydrochloric acid adaption,
      indicating induction of acid tolerance and enhancement adhesion in TWC01. Lactic
      acid treatment of TWC01 resulted in downregulation of channel protein and
      adherence-related protein expressions. CONCLUSION: The results of this study are
      helpful in understanding the resistance of locally isolated TWC01 to chemical and
      low-temperature stresses, and improving the control of this pathogen.

PMID- 24856425
TI  - Investigation of the case numbers of catheter-related bloodstream infection
      overestimated by the central line-associated bloodstream infection surveillance
      definition.
AB  - BACKGROUND/PURPOSE: Diagnosis of catheter-related bloodstream infection (CRBSI)
      requires specific laboratory evidence. A simpler definition, central line
      associated bloodstream infection (CLABSI), is recommended for surveillance
      purposes. Because exclusion of all other infection sources is difficult, CRBSI
      cases may be overestimated by using the CLABSI definition. METHODS: A
      retrospective observational study was performed at a regional hospital in
      southern Taiwan from September 2012 to December 2013. All 106 reported CLABSI
      cases were assessed. Cases with catheter tip cultures were reviewed. CRBSI was
      defined as the identification of same organisms from the paired blood and
      catheter tip cultures (>=15 colony-forming units) without evidence of secondary
      bacteremia from other infection sources. RESULTS: Overall, 64 cases were included
      and 31 (48.4%) were defined as CRBSI cases. In 30 (46.9%) cases, catheter tips
      were cultured after the corresponding blood cultures were performed. Later tip
      cultures were significantly more frequent in cases with other catheter types
      (18/22, 81.8%) than those with central lines (12/42, 28.6%; p < 0.0001). The same
      significant difference was also found among the CRBSI cases (central lines, 3/17,
      17.6%; others, 13/14, 92.9%; p < 0.00005). Twelve bacterial species were
      identified from the CRBSI cases, with Staphylococcus aureus being the most
      frequent (13, 41.9%), followed by Pseudomonas aeruginosa (5, 16.1%). CONCLUSION:
      The positive predictive value of the CLABSI definition for CRBSI cases was 48.4%.
      One should be aware of this discrepancy and should interpret the CLABSI
      surveillance definition with care.

PMID- 24856426
TI  - Anti-quorum sensing activity of flavonoid-rich fraction from Centella asiatica L.
      against Pseudomonas aeruginosa PAO1.
AB  - BACKGROUND/PURPOSE: Inhibition of quorum sensing (QS), a cell-density dependent
      regulation of gene expression in bacteria by autoinducers is an attractive
      strategy for the development of antipathogenic agents. METHODS: In this study,
      the anti-QS activity of the ethanolic extract of the traditional herb Centella
      asiatica was investigated by the biosensor bioassay using Chromobacterium
      violaceum CV026. The effect of ethyl acetate fraction (CEA) from the bioassay
      guided fractionation of ethanol extract on QS-regulated violacein production in
      C. violaceum ATCC12472 and pyocyanin production, proteolytic and elastolytic
      activities, swarming motility, and biofilm formation in Pseudomonas aeruginosa
      PAO1 were evaluated. Possible mechanism of QS-inhibitory action on autoinducer
      activity was determined by measuring the acyl homoserine lactone using C.
      violaceum ATCC31532. Anti-QS compounds in the CEA fraction were identified using
      thin layer chromatography biosensor overlay assay. RESULTS: Ethanol extract of C.
      asiatica showed QS inhibition in C. violaceum CV026. Bioassay-guided
      fractionation of ethanol extract revealed that CEA was four times more active
      than the ethanol extract. CEA, at 400 MUg/mL, completely inhibited violacein
      production in C. violaceum ATCC12472 without significantly affecting growth. CEA
      also showed inhibition of QS-regulated phenotypes, namely, pyocyanin production,
      elastolytic and proteolytic activities, swarming motility, and biofilm formation
      in P. aeruginosa PAO1 in a concentration-dependent manner. Thin layer
      chromatography of CEA with biosensor overlay showed anti-QS spot with an Rf value
      that corresponded with that of standard kaempferol. CONCLUSION: The anti-QS
      nature of C. asiatica herb can be further exploited for the formulation of drugs
      targeting bacterial infections where pathogenicity is mediated through QS.

PMID- 24856427
TI  - National action plan to eliminate central line-associated bloodstream infections
      in Taiwan.

PMID- 24856428
TI  - Arteriovenous fistula-related bacteremia caused by Achromobacter xylosoxidans in
      a uremic patient.

PMID- 24856432
TI  - Measles in pregnancy in Lyon France, 2011.
AB  - OBJECTIVE: To identify women who had measles while being pregnant during the 2011
      epidemic peak in Lyon, France, and to document maternal characteristics and fetal
      outcomes. METHODS: In a retrospective survey, women who had measles while being
      pregnant between January and December 2011 were identified from the records of
      the Laboratory of Virology, Hospices Civils de Lyon. Epidemiologic data, clinical
      characteristics, and measles outcomes were assessed. RESULTS: In total, 11
      pregnant women and 2 women who had just delivered were hospitalized with measles
      infection in Lyon. The most severe maternal complication was pneumonia, which
      occurred in 4 women (30.8%). Other maternal complications included fever (11
      women; 84.6%) and elevated liver enzymes (2/6 women; 33.3%). All women delivered
      healthy newborns. Post-exposure prophylaxis using human polyvalent immunoglobulin
      was initiated for three newborns whose mothers acquired measles in the immediate
      postpartum period. None of these newborns subsequently acquired measles, although
      breastfeeding was maintained. CONCLUSION: Although measles infections during
      pregnancy can have a deleterious effect on both mother and child, in many cases
      hospitalization is not required. Unnecessary admission should be avoided given
      the high risk of transmission of measles in an obstetrics ward.

PMID- 24856433
TI  - A randomized comparative trial of early initiation of oral maternal feeding
      versus conventional oral feeding after cesarean delivery.
AB  - OBJECTIVE: To compare the effects of two maternal feeding policies-early versus
      conventional oral feeding-after cesarean delivery. METHODS: This prospective
      multicenter randomized comparative trial was conducted at tertiary care hospitals
      in Sindh, Pakistan, from 2010 to 2012. Women with an uncomplicated cesarean
      delivery under spinal anesthesia were allocated to an intervention of early
      (after 2 hours) or conventional (after 18 hours) initiation of oral feeding.
      Outcomes included maternal ambulation, maternal satisfaction, gastrointestinal
      functions, and length of hospital stay. RESULTS: In total, 1174 women (n=587 per
      group) were included in the final analysis. Gastrointestinal complications were
      not significantly different between the two groups. Lower intensities of thirst
      and hunger and a higher rate of maternal satisfaction were observed in the early
      feeding group (P<0.05), and 53.8% of women in this group were able to ambulate
      within 15 hours of surgery, compared with 27.9% of women in the conventional
      feeding group. The frequencies of readmission, febrile morbidity, and wound
      infection were insignificant. CONCLUSION: Early oral dietary initiation after
      cesarean delivery resulted in early ambulation, greater maternal satisfaction,
      and reduced length of hospital stay, with no detrimental outcomes, making this
      practice cost-effective. Hence, day-care cesarean delivery might be an option in
      resource-constrained settings. TRIAL REGISTRATION NUMBER: ChiCTR-TRC-13003651,
      http://www.chictr.org.

PMID- 24856435
TI  - The unresolved debate on lowering the recommended dietary intake for folate.

PMID- 24856436
TI  - "I am dead to them": HIV-related stigma experienced by people living with HIV in
      Kerman, Iran.
AB  - People living with HIV (PLWH) are often subject to discrimination. The causes,
      types, and consequences of this stigma in Iran are not yet fully understood. In
      depth, semi-structured interviews were held with a purposively selected group of
      25 PLWH recruited from a triangular HIV clinic in Kerman, Iran. Almost all
      participants reported experiencing internal and external stigma in a variety of
      contexts. Participants mentioned at least three major types of internal stigma
      (silence, shame, and feeling miserable). PLWH also reported experiencing external
      stigma from their families, communities, and the health care system. While
      previous studies have demonstrated that the Iranian public has reported fairly
      positive attitudes toward PLWH, our participants' experiences tell a different
      story. Therefore, it is imperative to engage both public and private sectors in
      continuing education programs to reduce the level of stigma faced by PLWH. 

PMID- 24856438
TI  - An evaluation of the pharmacokinetics of methylphenidate for the treatment of
      attention-deficit/ hyperactivity disorder.
AB  - INTRODUCTION: Methylphenidate (MPH) plays a principal role in the multimodal
      treatment of attention-deficit/hyperactivity disorder (ADHD). Controlled studies
      have demonstrated an effective reduction in the core symptoms of the disorder
      following MPH therapy, although long-term studies also demonstrate that the
      therapeutic benefits dissipate in the absence of combined psychosocial
      interventions. AREAS COVERED: This review article focuses on the pharmacological
      characteristics of MPH, examining its effects on brain metabolism and the
      neurotransmitter system. Neuropsychological and clinical effects of different
      immediate and extended release MPH formulations are discussed to aid clinicians
      in choosing the appropriate formulation. The drug's addictive potency and abuse
      potential is also discussed. Data came from a literature search of relevant
      studies performed using the PubMed database up to June 2013. EXPERT OPINION: MPH
      is effective in the treatment of the core symptoms of ADHD. Considerable clinical
      expertise is required to identify an individually well-adapted dosage which will
      produce the optimal clinical effects with potential side effects minimized. Due
      to low adherence to medication, especially in adolescents, motivation to
      treatment and attentive clinical monitoring is mandatory, as is the consideration
      of risks of abuse or the presence of a comorbid addictive disorder.

PMID- 24856439
TI  - Sex differences and eating disorder risk among psychiatric conditions, compulsive
      behaviors and substance use in a screened Canadian national sample.
AB  - OBJECTIVE: This study examined sex differences and eating disorder risk among
      psychiatric conditions, compulsive behaviors (i.e., gambling, suicide thoughts
      and attempts) and substance use in a nationally representative sample. METHOD:
      Data from participants of the Canadian Community Health Survey Cycle 1.2 who
      completed the Eating Attitudes Test (n=5116) were analyzed. Sex differences were
      compared among psychiatric comorbidities according to eating disorder risk,
      binging, vomiting and dieting behavior. Poisson regression analysis provided
      prevalence ratios (PRs) of disordered eating adjusting for age, marital status,
      income, body mass index and recent distress. RESULTS: Pronounced sex differences
      were associated with eating disorder risk (PRs 4.89-11.04; all P values <.0001).
      Findings of particular interest included significantly higher PRs for eating
      disorder risk in males associated with gambling (PR 5.07, P<.0001) and for
      females associated with steroid and inhalant use as well as suicide thoughts and
      attempts (PRs 5.40-5.48, all P values <.0001). DISCUSSION: The findings from this
      detailed exploration of sex differences and eating disorder risk among
      psychiatric conditions, compulsive behaviors and substance use suggest that
      problem gambling, the use of inhalants and steroids and suicidal ideation in
      relationship to eating disorder risk warrant further investigation.

PMID- 24856441
TI  - Hematology clinic. Acute lymphoblastic leukemia.

PMID- 24856440
TI  - Guest editor's introduction: Energy homeostasis in context.
AB  - This article is part of a Special Issue "Energy Balance". Energy homeostasis is
      achieved through neuroendocrine and metabolic control of energy intake, storage,
      and expenditure. Traditionally, these controls have been studied in an
      unrealistic and narrow context. The appetite for food, for example, is most often
      assumed to be independent of other motivations, such as sexual desire,
      fearfulness, and competition. Furthermore, our understanding of all aspects of
      energy homeostasis is based on studying males of only a few species. The baseline
      control subjects are most often housed in enclosed spaces, with continuous,
      unlimited access to food. In the last century, this approach has generated useful
      information, but all the while, the global prevalence of obesity has increased
      and remains at unprecedented levels (Ogden et al., 2013, 2014). It is likely,
      however, that the mechanisms that control ingestive behavior were molded by
      evolutionary forces, and that few, if any vertebrate species evolved in the
      presence of a limitless food supply, in an enclosed 0.5 * 1 ft space, and exposed
      to a constant ambient temperature of 22+2  degrees C. This special issue of
      Hormones and Behavior therefore contains 9 review articles and 7 data articles
      that consider energy homeostasis within the context of other motivations and
      physiological processes, such as early development, sexual differentiation,
      sexual motivation, reproduction, seasonality, hibernation, and migration. Each
      article is focused on a different species or on a set of species, and most
      vertebrate classes are represented. Energy homeostasis is viewed in the context
      of the selection pressures that simultaneously molded multiple aspects of energy
      intake, storage, and expenditure. This approach yields surprising conclusions
      regarding the function of those traits and their underlying neuroendocrine
      mechanisms.

PMID- 24856443
TI  - Obstetric anaesthesia 2014: Dublin.

PMID- 24856442
TI  - Oxaliplatin-based chemotherapy: a new option in advanced hepatocellular
      carcinoma. a systematic review and pooled analysis.
AB  - Advanced hepatocellular carcinoma (HCC), for which locoregional treatment is not
      an option, is a candidate for palliative systemic therapy, but an accepted
      chemotherapy regimen does not exist. We have conducted a systematic literature
      review and meta-analyses to quantify the benefits of oxaliplatin (OXA)-based
      chemotherapy in advanced HCC in patients not exposed to sorafenib. Studies that
      enrolled advanced HCC patients treated with first-line OXA-based chemotherapy
      were identified using PubMed, Web of Science, SCOPUS, The Cochrane Register of
      Controlled Trials and EMBASE. A systematic review was conducted to calculate the
      pooled response rate and 95% confidence interval. The pooled median progression
      free survival (PFS) and overall survival, weighted on the number of patients of
      each selected trials, were also calculated. We tested for significant
      heterogeneity by Cochran's chi-squared test and I-square index. Thirteen studies
      were included in this review, with a total of 800 patients analysed. The pooled
      response rate was 16.8%. The median PFS and overall survival were 4.2 and 9.3
      months, respectively, with a 1 year overall survival of 37%. The weighted median
      PFS/overall survival and response rate were 4.5/11 months and 20% in Western
      patients. Conversely, in Asiatic studies, the median PFS/overall survival and
      response rate were 2.43/6.47 months and 13.2%, respectively. OXA-based
      chemotherapy is effective in advanced HCC and represents a viable option in these
      patients. A head to head comparison with sorafenib or a second-line agent should
      be verified in prospective trials. 

PMID- 24856445
TI  - Persisting arthralgia due to Mayaro virus infection in a traveler from Brazil: is
      there a risk for attendants to the 2014 FIFA World Cup?
AB  - The 2014 FIFA World Cup and the 2016 Olympic Games will attract large groups of
      visitors to Brazil. These visitors will be at risk for different arboviral
      infections, some of which not well known outside endemic areas. We report a case
      of a 52-year-old Dutch woman who presented with persistent arthralgia due to a
      Mayaro virus (MAYV) infection which she contracted in the Amazon basin in Brazil.
      MAYV is a mosquito-borne alphavirus which primarily circulates in humid tropical
      forests of South America. Infections are rarely reported in travelers and are
      characterized by an acute febrile illness which is often followed by a prolonged
      and sometimes incapacitating polyarthralgia. Both travelers and physicians should
      be aware of the risk of these arboviral infections and the importance of mosquito
      bite prevention should be stressed. 

PMID- 24856446
TI  - Chondritis or pseudochondritis?

PMID- 24856448
TI  - Motivational interviewing in the medical care setting.

PMID- 24856447
TI  - Quality of life, health status, and health service utilization related to a new
      measure of health literacy: FLIGHT/VIDAS.
AB  - OBJECTIVE: Researchers have identified significant limitations in some currently
      used measures of health literacy. The purpose of this paper is to present data on
      the relation of health-related quality of life, health status, and health service
      utilization to performance on a new measure of health literacy in a nonpatient
      population. METHODS: The new measure was administered to 475 English- and Spanish
      speaking community-dwelling volunteers along with existing measures of health
      literacy and assessments of health-related quality of life, health status, and
      healthcare service utilization. Relations among measures were assessed via
      correlations and health status and utilization was tested across levels of health
      literacy using ANCOVA models. RESULTS: The new health literacy measure is
      significantly related to existing measures of health literacy as well as to
      participants' health-related quality of life. Persons with lower levels of health
      literacy reported more health conditions, more frequent physical symptoms, and
      greater healthcare service utilization. CONCLUSION: The new measure of health
      literacy is valid and shows relations to measures of conceptually related
      constructs such as quality of life and health behaviors. PRACTICE IMPLICATIONS:
      FLIGHT/VIDAS may be useful to researchers and clinicians interested in a computer
      administered and scored measure of health literacy.

PMID- 24856450
TI  - Outcome of primary treatment of early laryngeal malignancies using photodynamic
      therapy.
AB  - CONCLUSION: Photodynamic therapy (PDT) is a viable and safe option for early
      laryngeal cancer that would be less suitably treated with radiation or trans-oral
      laser surgery (TLS). The cure rates with PDT appear to be comparable to those of
      conventional therapy, and the voice outcomes are also comparable. In the case of
      many sarcomas, PDT appears to be an organ- and function-sparing therapy, although
      it is more costly than other treatments. OBJECTIVES: The aim of this study was to
      show the results of PDT when it is used as a primary treatment of early laryngeal
      cancer. METHODS: We studied the results of PDT when used as a primary treatment.
      We looked at survival, effect on tumor, side effects, voice, and costs. RESULTS:
      The follow-up period was a median of 59 months. Nine of 10 patients were cured of
      their laryngeal cancer. PDT alone cured seven patients. All four of the sarcomas
      were cured using temoporfin. Two of three tumors that involved the anterior
      commissure were cured using only interstitial illumination with PDT. No serious
      side effects were noted. The patient's voices were improved after treatment in 5
      of 10 cases, and none had a worsened voice.

PMID- 24856449
TI  - Teachable moments for health behavior change and intermediate patient outcomes.
AB  - OBJECTIVE: Teachable moments (TM) are opportunities created through physician
      patient interaction and used to encourage patients to change unhealthy behaviors.
      We examine the effectiveness of TMs to increase patients' recall of advice,
      motivation to modify behavior, and behavior change. METHODS: A mixed-method
      observational study of 811 patient visits to 28 primary care clinicians used
      audio-recordings of visits to identify TMs and other types of advice in health
      behavior change talk. Patient surveys assessed smoking, exercise, fruit/vegetable
      consumption, height, weight, and readiness for change prior to the observed visit
      and 6-weeks post-visit. RESULTS: Compared to other identified categories of
      advice (i.e. missed opportunities or teachable moment attempts), recall was
      greatest after TMs occurred (83% vs. 49-74%). TMs had the greatest proportion of
      patients change in importance and confidence and increase readiness to change;
      however differences were small. TMs had greater positive behavior change scores
      than other categories of advice; however, this pattern was statistically non
      significant and was not observed for BMI change. CONCLUSION: TMs have a greater
      positive influence on several intermediate markers of patient behavior change
      compared to other categories of advice. PRACTICE IMPLICATIONS: TMs show promise
      as an approach for clinicians to discuss behavior change with patients
      efficiently and effectively.

PMID- 24856451
TI  - Endoscopic evidence of reflux disease in the larynx.
AB  - CONCLUSION: The severity of laryngeal mucosal lesions in patients with
      gastroesophageal reflux disease (GERD) is significantly greater than in controls.
      A higher degree of laryngeal mucosal injury is documented in patients in whom
      GERD is associated with more advanced esophageal lesions. OBJECTIVES: (1) To
      confirm the presence of inflammatory lesions in the laryngopharynx of patients
      with GERD. (2) To analyze the relationship between the severity of
      laryngopharyngeal and esophageal lesions on the basis of the reflux finding score
      (RFS) and the Los Angeles (LA) scale of esophageal mucosal injury. METHODS: The
      study included 92 subjects, among them 46 patients with GERD and 46 individuals
      without endoscopic evidence of esophageal lesions, qualified for routine
      endoscopy due to other indications. The endoscopic images of the inferior
      pharynx, larynx, and esophagus were analyzed during the video-endoscopic
      examination of the upper gastrointestinal tract. The laryngeal images were
      assessed according to RFS criteria and the numeric value of RFS was calculated.
      The degree of esophageal mucosal injury was described according to the LA scale.
      RESULTS: Both global RFS score and the scores of all RFS parameters except the
      presence of granulomatous tissue were significantly higher in patients with GERD
      than in the controls. Patients in whom GERD was associated with more severe
      esophageal lesions (group B according to the LA scale) had significantly higher
      global RFS score and scores of all analyzed parameters of laryngeal injury except
      subglottic edema than individuals in whom the degree of esophageal involvement
      was classified as group A.

PMID- 24856452
TI  - MET-COFEA: a liquid chromatography/mass spectrometry data processing platform for
      metabolite compound feature extraction and annotation.
AB  - In this paper, we present a novel liquid chromatography/mass spectrometry (LC/MS)
      data processing and analysis platform, MET-COFEA (METabolite COmpound Feature
      Extraction and Annotation). MET-COFEA detects and clusters chromatographic peak
      features for each metabolite compound by first comprehensively evaluating
      retention time and peak shape criteria and then annotating the associations
      between each peak's observed m/z value with the corresponding metabolite
      compound's molecular mass. MET-COFEA integrates a series of innovative
      approaches, including novel mass trace based extracted-ion chromatogram (EIC)
      extraction, continuous wavelet transform (CWT)-based peak detection, and compound
      associated peak clustering and peak annotation algorithms. On the basis of the
      deduced neutral molecular mass and retention time, we have also developed a new
      alignment algorithm that uses compound-associated peak groups instead of
      individual peaks to align the same metabolite compound across samples from
      different electrospray ionization (ESI) modes, different instruments, even
      different experimental conditions. MET-COFEA has been systematically tested on a
      series of LC/MS profiles of mixed standards at different concentrations as well
      as real untargeted LC/MS plant metabolomics data. We compared the performances of
      MET-COFEA with the existing publicly available tools at LC/MS peak analysis level
      and demonstrated its excellent performance in this arena. MET-COFEA is freely
      available at http://bioinfo.noble.org/manuscript-support/met-cofea/.

PMID- 24856453
TI  - Comparison of meniscal fibrochondrocyte and synoviocyte bioscaffolds toward
      meniscal tissue engineering in the dog.
AB  - Tissue engineering is a promising field of study toward curing the meniscal
      deficient stifle; however the ideal cell type for this task is not known. We
      describe here the extraction of synoviocytes and meniscal fibrochondrocytes from
      arthroscopic debris from six dogs, which were cultured as tensioned bioscaffolds
      to synthesize meniscal-like fibrocartilage sheets. Despite the diseased status of
      the original tissues, synoviocytes and meniscal fibrochondrocytes had high
      viability at the time of removal from the joint. Glycosaminoglycan and collagen
      content of bioscaffolds did not differ. Meniscal fibrochondrocyte bioscaffolds
      contained more type II collagen, but collagen deposition was disorganized, with
      only 30-40% of cells viable. The collagen of synoviocyte bioscaffolds was
      organized into sheets and bands and 80-90% of cells were viable. Autologous,
      diseased meniscal fibrochondrocytes and synoviocytes are plausible cell sources
      for future meniscal tissue engineering research, however cell viability of
      meniscal fibrochondrocytes in the tensioned bioscaffolds was low. 

PMID- 24856454
TI  - Hyperostotic bone disease in a wombat (Vombatus ursinus).
AB  - Little is known about wombat diseases in general, and about their congenital
      diseases in particular. In the current study, the skeleton of a common wombat
      (Vombatus ursinus) that exhibited generalized hyperostosis is analyzed, and
      possible diagnoses are reviewed. Macromorphological analyses revealed that the
      diaphyses of the long bones manifested an increased diameter with extensive
      diaphyseal new-bone formation (periosteal and endosteal). Cross-sections of the
      diaphyses showed that the cortical-medullary demarcation was indistinct. The
      calvarial bones were thickened. Radiographs showed uniform sclerosis of the long
      bones with loss of trabecular pattern. Microradiography showed extensive bone
      remodeling, a hyper-vascularized lamellated layer of bone and numerous linear
      formation defects. Possible causes for the lesions, including sclerosing bone
      dysplasia disorders, acquired syndromes causing hyperostosis, and metabolic
      diseases typical of animals in captivity, are discussed. 

PMID- 24856455
TI  - Co-expression of EtMic2 protein and chicken interleukin-18 for DNA vaccine
      against chicken coccidiosis.
AB  - In the present study, a naked EtMIC2 DNA vaccine, a ChIL-18 expression vector and
      a EtMIC2 and ChIL-18 co-expression DNA vaccine were constructed and their
      protective efficacies against homologous challenge were compared and evaluated by
      examining the body weight gain, oocyst shedding, cecal lesion, ACI as well as
      specific anti-EtMic2 antibody level, the proliferation ability and percentages of
      CD4+ and CD8+ of splenocytes. The results showed the naked EtMIC2 DNA vaccine
      could increase the weight gain and decrease the oocyst shedding, but could not
      alleviate the cecal lesion of immunized chickens compared to unimmunized
      chickens. Chickens immunized with the co-expression vector pVAX1-MIC2-IL-18
      exhibited much improved immune protection against challenge compared to chickens
      immunized with naked EtMIC2 DNA vaccine, or with naked EtMIC2 DNA vaccine and
      ChIL-18 expression vector applied separately. These results suggest that the co
      expression of ChIL-18 with EtMic2 together could significantly improve the immune
      protection of the EtMic2 protein. 

PMID- 24856456
TI  - An outbreak of massive mortality among farm rabbits associated with
      Cryptosporidium infection.
AB  - Cryptosporidium in farm rabbits is not often recognised due to a low prevalence
      and asymptomatic course of infection. Nonetheless, incidences of fatal diarrhoeic
      diseases are frequently noticed in the rabbitries. In this article, we report an
      outbreak where there was massive mortality among farm rabbits associated with
      Cryptosporidium infection. The disease was characterised by profuse diarrhoea
      resulting in the death of rabbits. A pooled faecal sample was screened for a
      presence of parasites using microscopy methods. In the tested sample no other
      parasites other than Cryptosporidium oocysts were found. Further identification
      of the parasite species was performed at a molecular level, using the 18 SSU
      rRNA, COWP and LIB13 PCR followed by a subtyping at the GP60 gene locus. Sequence
      analysis of GP60 gene fragment revealed the presence of a novel subtype VbA24 of
      Cryptosporidium cuniculus. In this outbreak a Cryptosporidium protozoan parasite
      played a major role in the etiology of the gastrointestinal disorders in rabbits
      resulting in massive mortality of the infected animals. 

PMID- 24856457
TI  - [Lung is also involved in juvenile dermatomyositis].
AB  - Juvenile dermatomyositis is the leading cause of chronic idiopathic inflammatory
      myopathy of auto-immune origin in children. Lung involvement in inflammatory
      myopathies is well described in adults, involving mostly interstitial lung
      disease, aspiration pneumonia and alveolar hypoventilation. We propose to
      describe its specificities in children. Pulmonary involvement may be asymptomatic
      and therefore must be systematically screened for. In case of clinical or
      functional respiratory abnormality, a chest computed tomographic (CT) scan is
      necessary. In children, a decrease of respiratory muscle strength seems common
      and should be systematically and specifically searched for by non-invasive and
      reproducible tests (sniff test). Interstitial lung disease usually associates
      restrictive functional defect, impairment of carbon monoxide diffusion and
      interstitial lung disease on CT scan. As in adults, the first-line treatment of
      juvenile dermatomyositis is based on corticosteroids. Corticosteroid resistant
      forms require corticosteroid bolus or adjuvant immunosuppressive drugs
      (methotrexate or cyclosporine). There is no consensus in pediatrics for the
      treatment of diffuse interstitial lung disease. Complications of treatment,
      including prolonged steroid therapy, are frequent and therefore a careful
      assessment of the treatments risk-benefit ratio is necessary, especially in
      growing children. 

PMID- 24856458
TI  - Electro- and magneto-encephalographic spike source localization of small focal
      cortical dysplasia in the dorsal peri-rolandic region.
AB  - OBJECTIVE: Small focal cortical dysplasia (FCD) may be ambiguous or overlooked on
      magnetic resonance (MR) imaging. Source localization of EEG and
      magnetoencephalography (MEG) spikes was evaluated to confirm the diagnosis of
      small FCD. METHODS: This study included 6 epilepsy patients with a single small
      lesion on MR imaging suggesting FCD within a single gyrus among 181 consecutive
      epilepsy patients admitted to our epilepsy monitoring unit over 27 months.
      Stereotypical interictal spikes were detected on simultaneous EEG and MEG
      recordings and the onset-related source of averaged spikes was estimated.
      RESULTS: All 6 patients had unique clinical characteristics as follows: leg
      sensori-motor seizures in 5 patients and eye version in 1 patient; a small MR
      imaging lesion suggesting FCD in the dorsal peri-rolandic region, which had been
      overlooked until our evaluation; and both EEG and MEG dipoles were estimated
      adjacent to the MR imaging lesion. CONCLUSIONS: Source localization of EEG and
      MEG spikes can confirm the diagnosis of FCD based on a single small MR imaging
      lesion, which was overlooked by previous examination of MR images. SIGNIFICANCE:
      Examination of MR images should be based on spike source localization as well as
      seizure semiology to identify subtle MR imaging abnormalities.

PMID- 24856459
TI  - Impact of sleep on the localizing value of video EEG in patients with refractory
      focal seizures - a prospective video-EEG with EOG and submental EMG study.
AB  - OBJECTIVES: To examine the role of sleep and its stages on the localizing value
      of video EEG in the evaluation of refractory focal seizures. METHODS: Video
      electroencephalographic (VEEG) evaluation with additional polygraphic recording
      was carried out for 70 consecutive patients with refractory focal epilepsy,
      undergoing pre-surgical evaluation, over a two-year period. Localization of video
      EEG for each seizure was made based on clinical, ictal and interictal data.
      Seizure localization in each patient was assessed for concordance with MRI and
      other imaging data (SPECT, PET) for both wake and sleep seizures. Interictal
      discharges in sleep and wake were similarly compared for concordance with imaging
      data. RESULTS: A total of 608 seizures were recorded in 70 patients, 289 in
      sleep. Overall, concordance with imaging data was found in 218 out of 322 wake
      seizures (67.8%) and in 157 out of 286 sleep seizures (54.8%) (p=0.0314). On
      analyzing the subset of patients with seizures recorded in both wake and sleep
      states (total 279 seizures recorded, 113 out of sleep), concordance was observed
      in 93 out of 166 (56%) wake seizures and in 80 out of 113 (70.7%) sleep seizures
      (OR 2.03, 95% CI 1.17 to 3.56; p 0.007). Interictal discharges were more common
      and more precisely localizing in sleep, mostly in stage N2. CONCLUSIONS: This
      prospective VEEG-PSG study demonstrates the role of sleep versus wake state in
      the localizing value of different components of long-term VEEG recording for
      patients with medically refractory epilepsy. Our findings show that while wake
      state ictal EEG has more localizing value in a mixed group of patients, sleep
      ictal and interictal EEG is significantly more useful in patients who have
      seizures recorded both during wake and sleep states. In addition, interictal
      discharges recorded during NREM sleep have high localizing value. SIGNIFICANCE:
      This is only the second study elucidating the effect of sleep on the localizing
      value of video-electroencephalographic evaluation of patients with medically
      refractory focal epilepsy; mainly revealing high value of sleep interictal
      discharges and that sleep ictal recording has two times higher localizing value
      than wake ictal recording, among patients in whom seizures are recorded in both
      states.

PMID- 24856461
TI  - The effect of anodal transcranial direct current stimulation over the primary
      motor or somatosensory cortices on somatosensory evoked magnetic fields.
AB  - OBJECTIVES: The purpose of this study was to investigate the effect of anodal
      transcranial direct-current stimulation (tDCS) applied over the primary motor
      (M1) or the primary somatosensory (S1) cortices on somatosensory evoked magnetic
      fields (SEFs) following median nerve stimulation. METHODS: Anodal tDCS was
      applied for 15min on the left motor or somatosensory cortices at 1mA. SEFs were
      recorded following right median nerve stimulation using a magnetoencephalography
      (MEG) system before and after the application of tDCS. SEFs was measured and
      compared before and after tDCS was applied over M1 or S1. RESULTS: The source
      strengths for the P35m and P60m increased after tDCS was applied over M1 and that
      for the P60m increased after tDCS was applied over S1. The mean equivalent
      current dipole (ECD) location for the P35m was located significantly anterior to
      that of the N20m, but only during post 1 (10-20min after tDCS was applied over
      M1). CONCLUSION: Our results indicated that the anodal tDCS applied over M1
      affected the P35m and P60m sources on SEF components, while that applied over S1
      influenced the P60m source. SIGNIFICANCE: We demonstrated anodal tDCS applied
      over M1 or S1 can modulate somatosensory processing and components of SEFs,
      confirming the hypothesis for locally distinct generators of the P35m and P60m
      sources.

PMID- 24856460
TI  - Lateralization and localization of epilepsy related hemodynamic foci using
      presurgical fMRI.
AB  - OBJECTIVE: The aim was to develop a method for the purpose of localizing epilepsy
      related hemodynamic foci for patients suffering intractable focal epilepsy using
      task-free fMRI alone. METHODS: We studied three groups of subjects: patients with
      intractable focal epilepsy, healthy volunteers performing motor tasks, and
      healthy volunteers in resting state. We performed spatial independent component
      analysis (ICA) on the fMRI alone data and developed a set of IC selection
      criteria to identify epilepsy related ICs. The method was then tested in the two
      healthy groups. RESULTS: In seven out of the nine surgery patients, identified
      ICs were concordant with surgical resection. Our results were also consistent
      with presurgical evaluation of the remaining one patient without surgery and may
      explain why she was not suitable for resection treatment. In the motor task study
      of ten healthy subjects, our method revealed components with concordant spatial
      and temporal features as expected from the unilateral motor tasks. In the resting
      state study of seven healthy subjects, the method successfully rejected all
      components in four out of seven subjects as non-epilepsy related components.
      CONCLUSION: These results suggest the lateralization and localization value of
      fMRI alone in presurgical evaluation for patients with intractable unilateral
      focal epilepsy. SIGNIFICANCE: The proposed method is noninvasive in nature and
      easy to implement. It has the potential to be incorporated in current presurgical
      workup for treating intractable focal epilepsy patients.

PMID- 24856462
TI  - Unraveling tissue repair immune responses in flies.
AB  - Drosophila melanogaster has emerged as a powerful model to understand innate
      immune responses to infection (note the 2011 Nobel Prize in Physiology or
      Medicine), and in recent years this system has begun to inform on the role and
      regulation of immune responses during tissue injury. Due to the speed and
      complexity of inflammation signals upon damage, a complete understanding of the
      immune responses during repair requires a combination of live imaging at high
      temporal resolution and genetic dissection, which is possible in a number of
      different injury models in the fly. Here we discuss the range of wound-induced
      immune responses that can be modeled in flies. These wound models have revealed
      the most immediate signals leading to immune cell activation, and highlighted a
      number of complex signaling cascades required for subsequent injury-associated
      inflammatory responses. What has emerged from this system are a host of both
      local acting signals, and surprisingly, more systemic tissue repair immune
      responses. 

PMID- 24856463
TI  - Effects of work and life stress on semen quality.
AB  - OBJECTIVE: To evaluate associations between work-related stress, stressful life
      events, and perceived stress and semen quality. DESIGN: Cross-sectional analysis.
      SETTING: Northern California. PATIENT(S): 193 men from the Child Health and
      Development Studies evaluated between 2005-2008. INTERVENTION(S): None. MAIN
      OUTCOME MEASURE(S): Measures of stress including job strain, perceived stress,
      and stressful life events; outcome measures of sperm concentration, percentage of
      motile sperm, and percentage of morphologically normal sperm. RESULT(S): We found
      an inverse association between perceived stress score and sperm concentration
      (estimated coefficient b=-0.09*10(3)/mL; 95% confidence interval [CI]=-0.18, 
      0.01), motility (b=-0.39; 95% CI=-0.79, 0.01), and morphology (b=-0.14; 95% CI, 
      0.25, -0.04) in covariate-adjusted linear regression analyses. Men who
      experienced two or more stressful life events in the past year compared with no
      stressful events had a lower percentage of motile sperm (b=-8.22; 95% CI, -14.31,
      -2.13) and a lower percentage of morphologically normal sperm (b=-1.66; 95% CI, 
      3.35, 0.03) but a similar sperm concentration. Job strain was not associated with
      semen parameters. CONCLUSION(S): In this first study to examine all three domains
      of stress, perceived stress and stressful life events but not work-related stress
      were associated with semen quality.

PMID- 24856464
TI  - Effectiveness of different routes of misoprostol administration before operative
      hysteroscopy: a randomized, controlled trial.
AB  - OBJECTIVE: To compare the effectiveness and patient preference of different
      routes of misoprostol administration before operative hysteroscopy in
      premenopausal women. DESIGN: Randomized, controlled trial. SETTING: University
      hospital. PATIENT(S): One hundred sixty women undergoing operative hysteroscopy.
      INTERVENTION(S): Patients were randomly assigned to receive 400 MUg misoprostol
      orally (n=40), sublingually (n=40), or vaginally (n=40) before operative
      hysteroscopy; the control group (n=40) did not receive any cervical priming
      agent. MAIN OUTCOME MEASURE(S): Preoperative cervical width, adverse effects, and
      patient preference. RESULT(S): The mean (+/-SD) cervical widths for the oral,
      sublingual, vaginal, and control groups were 7.62+/-1.81 mm, 7.58+/-1.77 mm,
      7.60+/-2.15 mm, and 5.65+/-2.12 mm, respectively, which was statistically
      significant. Time to cervical dilatation was also significantly longer in the
      control group than in the other three groups. Misoprostol-related adverse effects
      and hysteroscopy-related complications were comparable among the four study
      groups. Of all 160 subjects, 132 (82%) preferred the oral route for misoprostol
      administration to the sublingual or vaginal routes, or had no preference.
      CONCLUSION(S): All orally, sublingually, and vaginally administrated misoprostol
      is equally effective in inducing proper cervical priming before operative
      hysteroscopy. Considering patient preference, oral administration may be the
      optimal route for misoprostol administration. CLINICAL TRIAL REGISTRATION NUMBER:
      NCT01805115.

PMID- 24856466
TI  - Lynx reproduction--long-lasting life cycle of corpora lutea in a feline species.
AB  - A review of lynxes' reproductive biology and comparison between the reproductive
      cycles of the domestic cat and lynxes is presented. Three of the four lynx
      species (the bobcat excluded) express quite similar reproductive pattern (age at
      sexual maturity, estrus and pregnancy length, litter size). Similarly to the
      domestic cat, the bobcat is polyestric and can have more than one litter per
      year. Domestic cats and many other felid species are known to express
      anovulatory, pregnant and pseudo-pregnant reproductive cycles in dependence on
      ovulation induction and fertilization. The formation of corpora lutea (CLs)
      occurs after ovulation. In pregnant animals, luteal function ends with
      parturition, whereas during pseudo-pregnancy a shorter life span and lower
      hormone secretion are observed. The life cycle of corpora lutea in Eurasian
      lynxes is different from the pattern described in domestic cats. Lynx CLs produce
      progestagens in distinctive amounts permanently for at least two years,
      regardless of their origin (pregnancy or pseudo-pregnancy). It is suggested that
      long-lasting CLs induce a negative feedback to inactivate folliculogenesis,
      turning a normally polyestric cycle observed in most felids into a monoestric
      cycle in lynxes.

PMID- 24856465
TI  - Ever-changing cell interactions during the life span of the corpus luteum:
      relevance to luteal regression.
AB  - The corpus luteum (CL) undergoes dramatic morphological and functional changes
      throughout its lifespan. It initially develops from cells that remain in the
      follicle following ovulation. Eventually the mature CL is composed of multiple,
      distinctive cell types including steroidogenic cells (small and large luteal
      cells) and other cell types (endothelial cells, pericytes, fibroblasts, and
      immune cells). Robust angiogenesis accompanies CL formation, establishing an
      elaborate blood vessel network at mid cycle. In the absence of embryonic signals,
      the CL will regress in a process triggered by prostaglandin F2alpha (PG). Luteal
      demise in the responsive gland is characterized by cessation of steroid
      production, angio-regression, and apoptotic cell death, brought about by
      leukocyte infiltration, inflammatory responses, and diminished angiogenic
      support. However, the young immature CL is resistant or refractory to the
      luteolytic actions of PG. Evidence based on functional genomics and other studies
      highlight the roles played by endothelial, immune, and steroidogenic luteal cells
      and their interactions in the PG-responsive vs. PG-refractory CL.

PMID- 24856467
TI  - Luteal regression vs. prepartum luteolysis: regulatory mechanisms governing
      canine corpus luteum function.
AB  - Canine reproductive physiology exhibits several unusual features. Among the most
      interesting of these are the lack of an acute luteolytic mechanism, coinciding
      with the apparent luteal independency of a uterine luteolysin in absence of
      pregnancy, contrasting with the acute prepartum luteolysis observed in pregnant
      animals. These features indicate the existence of mechanisms different from those
      in other species for regulating the extended luteal regression observed in non
      pregnant dogs, and the actively regulated termination of luteal function observed
      prepartum as a prerequisite for parturition. Nevertheless, the supply of
      progesterone (P4) depends on corpora lutea (CL) as its primary source in both
      conditions, resulting in P4 levels that are similar in pregnant and non-pregnant
      bitches during almost the entire luteal life span prior to the prepartum
      luteolysis. Consequently, the duration of the prolonged luteal phase in non
      pregnant bitches frequently exceeds that of pregnant ones, which is a peculiarity
      when compared with other domestic animal species. Both LH and prolactin (PRL) are
      endocrine luteotrophic factors in the dog, the latter being the predominant one.
      In spite of increased availability of these hormones, luteal
      regression/luteolysis still takes place. Recently, possible mechanisms regulating
      the expression and function of PRL receptor have been implicated in the local,
      i.e., intraluteal regulation of PRL bioavailability and thus its steroidogenic
      potential. Similar mechanisms may relate to the luteal LH receptor. Most
      recently, evidence has been provided for an autocrine/paracrine role of
      prostaglandin E2 (PGE2) as a luteotrophic factor in the canine CL acting at the
      level of steroidogenic acute regulatory (STAR)-protein mediated supply of
      steroidogenic substrate, without having a significant impact on the enzymatic
      activity of the respective steroidogenic enzymes, 3beta-hydroxysteroid
      dehydrogenase (3betaHSD, HSD3B2) and cytochrome P450 side-chain cleavage enzyme
      (P450scc, CYP11A1). Together with the strongly time-dependent expression of
      prostaglandin transporter, luteal prostaglandins seem to be involved more in the
      process of luteal formation than in termination of CL function in the dog. The
      possible roles of other factors such as vasoactive compounds, growth factors or
      cytokines have not been extensively studied but should not be neglected.

PMID- 24856468
TI  - Evaluation of bovine luteal blood flow by using color Doppler ultrasonography.
AB  - Since luteal vascularization plays a decisive role for the function of the corpus
      luteum (CL), the investigation of luteal blood flow (LBF) might give valuable
      information about the physiology and patho-physiology of the CL. To quantify LBF,
      usually Power mode color Doppler ultrasonography is used. This method detects the
      number of red blood cells moving through the vessels and shows them as color
      pixels on the B-mode image of the CL. The area of color pixels is measured with
      computer-assisted image analysis software and is used as a semiquantitative
      parameter for the assessment of LBF. Although Power mode is superior for the
      evaluation of LBF compared to conventional color Doppler ultrasonography, which
      detects the velocity of blood cells, it is still not sufficiently sensitive to
      detect the blood flow in the small vessels in the center of the bovine CL.
      Therefore, blood flow can only be measured in the bigger luteal vessels in the
      outer edge of the CL. Color Doppler ultrasonographic studies of the bovine
      estrous cycle have shown that plasma progesterone (P4) concentration can be more
      reliably predicted by LBF than by luteal size (LS), especially during the CL
      regression. During the midluteal phase, cows with low P4 level showed smaller CL,
      but LBF, related to LS, did not differ between cows with low and high P4 levels.
      In contrast to non-pregnant cows, a significant rise in LBF was observed three
      weeks after insemination in pregnant cows. However, LBF was not useful for an
      early pregnancy diagnosis due to high LBF variation among cows. When the effects
      of an acute systemic inflammation and exogenous hormones on the CL are examined,
      the LBF determination is more sensitive than LS assessment. In conclusion, color
      Doppler ultrasonography of the bovine CL provides additional information on
      luteal function compared to measurements of LS and plasma P4, but its value as a
      parameter concerning assessment of fertility in cows has to be clarified.

PMID- 24856469
TI  - 3D ultrasound imaging of the human corpus luteum.
AB  - The aim of this article was to present the extent to which the state-of-the art
      ultrasonographic imaging can be used to visualize the features of the human
      corpus luteum (CL). In the late 1970s, the first ultrasonographic images of human
      CLs were published. The advent of transvaginal, high-resolution transducers has
      greatly improved the quality of imaging as did the subsequent introduction of
      color Doppler and 3D ultrasonography. In the present technical note, the examples
      of the various technical and imaging modalities used to examine the human CLs are
      shown. CL is a short-lived structure with a highly variable morphological
      appearance and the 3D ultrasonographic technique is an ideal tool to perform
      standardized measurements on the CL. The introduction of new imaging techniques
      in clinical reproductive medicine can only be successful if operators are
      properly trained.

PMID- 24856470
TI  - Different expression of PGE synthase, PGF receptor, TNF, Fas and oxytocin in the
      bovine corpus luteum of the estrous cycle and pregnancy.
AB  - Functional differences between the corpus luteum (CL) of pregnancy and CL of the
      cycle in cows were examined. Messenger RNA and protein levels of prostaglandin
      (PG) E synthase (PGES), PGF2alpha receptor (PGFR), tumor necrosis factor-alpha
      (TNF) and Fas were found to be higher in the CL of pregnancy than in CL of the
      cycle. Oxytocin (OT) mRNA and protein levels were lower in the CL of pregnancy.
      Messenger RNA levels of progesterone receptor (PR), luteinizing hormone receptor
      (LHR), PGE2 receptor (PGER), PGF synthase (PGFS), TNF receptor type I (TNFRI) and
      TNF receptor type II (TNFRII) did not differ between the cycle and pregnancy.
      PGE2 and PGF2alpha production by cultured bovine endometrial tissues was
      decreased by a supernatant derived from the homogenized CL of pregnancy but not
      by that of the CL of the cycle, suggesting that specific substances in the CL of
      pregnancy affect endometrial PG production in cows. Collectively, PGES, PGFR,
      TNF, Fas or OT may contribute to differences between the CL of pregnancy and CL
      of the estrous cycle in cows.

PMID- 24856471
TI  - The effects of EGF and IGF-1 on FSH-mediated in vitro maturation of domestic cat
      oocytes derived from follicular and luteal stages.
AB  - The objective of this study was to evaluate the influence of epidermal growth
      factor (EGF) and insulin like growth factor-I (IGF-1) on the in vitro maturation
      of cat oocytes recovered from follicular and luteal stage ovaries. Oocytes from
      follicular (n=580) and luteal (n=209) stages were harvested and divided into four
      groups, which were cultured in FSH-mediated maturation medium supplemented with:
      (1) EGF alone (25ng/mL); (2) IGF-1 alone (100ng/mL); (3) EGF+IGF-1 (25ng/mL
      EGF+100ng/mL IGF-I); or (4) no growth factor (control). The proportion of
      follicular stage oocytes reaching the metaphase II stage was significantly higher
      than that of oocytes obtained at the luteal stage in both control and study
      groups (p<0.001). The percentages of oocytes reaching the metaphase II stage
      during the follicular period were 62.6% in control; 70.9% in EGF; 72.8% in IGF-1,
      and 78.1% in EGF+IGF-1 groups, whereas the respective values for gametes
      collected from luteal stage ovaries were 12.5%, 17.5%, 12.5%, and 16.9%.
      Additionally, the differences between the study and control groups were
      significant in the case of follicular stage oocytes. Finally, supplementing the
      maturation medium with EGF and/or IGF-1 significantly enhanced the meiotic
      maturation of oocytes recovered from follicular stage ovaries. The present study
      also demonstrated that the combination of EGF and IGF-I provides an additional or
      synergic effect on meiotic maturation of oocytes recovered from the follicular
      stage.

PMID- 24856472
TI  - Biological transcomplementary activation as a novel and effective strategy
      applied to the generation of porcine somatic cell cloned embryos.
AB  - A novel method termed the biological transcomplementary activation (B-TCA) has
      been recently utilized for the stimulation of porcine oocytes reconstituted by
      somatic cell nuclear transfer (SCNT). The use of cytosolic components originating
      from fertilized (FE) rabbit zygotes as the stimuli for the B-TCA of SCNT-derived
      pig oocytes appeared to be a highly efficient strategy applied to promote the in
      vitro development of cloned embryos, leading to a significant improvement in the
      blastocyst yield (43.6%) compared to the yields achieved using the standard
      protocol of simultaneous fusion and electrical activation (SF-EA; [31.3%]) or the
      protocol of delayed electrical activation (D-EA) independent of extracellular
      Ca(2+) ions (0%). The FE rabbit zygote cytoplast-mediated B-TCA resulted in the
      increased blastocyst formation rate of porcine cloned embryos as compared to the
      B-TCA triggered by either cytoplasts isolated from pig parthenogenotes (PAs;
      [27.8%]) or rabbit PA-descended cytoplasts (0%). A considerably lower percentage
      of blastocysts containing apoptotic and/or necrotic (annexin V-eGFP-positive)
      cells were obtained from the SCNT-derived oocytes stimulated by the FE rabbit
      zygote cytoplast-based B-TCA (22.2%) compared to those stimulated using the SF-EA
      protocol (35.1%). In contrast to the B-TCA induced by FE rabbit zygote
      cytoplasts, apoptosis/necrosis incidence decreased totally among the cloned pig
      blastocysts that developed from reconstituted oocytes undergoing the porcine PA
      cytoplast-evoked B-TCA. In conclusion, the FE rabbit zygote cytoplast-mediated B
      TCA turned out to be a relatively effective strategy for the in vitro production
      of porcine blastocyst clones of higher quality compared to those created using
      the standard SF-EA approach.

PMID- 24856473
TI  - Expression of urocortin and its receptors in the rat epididymis.
AB  - Urocortin (UCN; 40 aa) is a corticotrophin-releasing hormone (CRH)-related
      peptide. The biological actions of CRH family peptides are mediated by two types
      of G-protein-coupled receptors, CRH type 1 receptor (CRHR1) and CRH type 2
      receptor (CRHR2). The biological effects of the peptides are mediated and
      modulated not only by CRH receptors but also by a highly conserved CRH-binding
      protein (CRHBP). The aim of the present study was to investigate the expression
      of UCN, CRHR1, CRHR2 and CRHBP by immunohistochemistry, Western blot, RT-PCR and
      real-time RT-PCR in the rat epididymis. Urocortin, CRHR1 and CRHR2, but not
      CRHBP, were expressed in all segments of the rat epididymis. Specifically, UCN-
      and CRHR2-immunoreactivities (IRs) were distributed in epididymal epithelial
      cells of the caput, corpus and cauda. CRHR1-IR was found in the fibromuscular
      cells surrounding the epididymal duct and in the smooth musculature of the blood
      vessels throughout the organ. UCN and CRHR2 mRNA expression levels were higher in
      the caput and corpus than in the cauda, while CRHR1 mRNA level was higher in the
      cauda than those in the caput and corpus. In summary, UCN, CRHR1 and CRHR2 are
      expressed in the rat epididymis. It is suggested that CRH-related peptides might
      play multiple roles in the maturation and storage of spermatozoa.

PMID- 24856474
TI  - Lactoferrin expression and secretion in the stallion epididymis.
AB  - Lactoferrin is one of the most abundant proteins secreted by the stallion
      epididymis, but its cellular localization and regulation remain unknown. This
      study was designed to address the following objectives: (1) identify the
      epididymal cell types producing lactoferrin in pre-pubertal, peri-pubertal and
      post-pubertal animals; (2) demonstrate that lactoferrin binds to stallion sperm;
      and (3) determine if testosterone and estradiol regulate lactoferrin secretion in
      vitro. Using an immunohistochemical method, lactoferrin was localized in the
      cytoplasm of principal cells in the corpus and cauda of peri- and post-pubertal
      animals. The epididymis of pre-pubertal animals did not express lactoferrin.
      Immunolabeling of lactoferrin was also observed on the mid-piece and tail of the
      sperm. The role of estradiol and testosterone in regulating secretion of
      lactoferrin in the post-pubertal epididymis was investigated using tissue culture
      methods. Lactoferrin concentration in the culture media was determined by
      validated enzyme-linked immunosorbent assays (ELISA). Testosterone did not
      increase the concentration of lactoferrin in the media in any epididymal region.
      In contrast, estradiol-17beta significantly increased the concentration of
      lactoferrin in the media containing tissue from the cauda. In conclusion, the
      expression of lactoferrin was found in the cytoplasm of principal cells in the
      corpus and cauda of the epididymis in peri- and post-pubertal stallions but not
      pre-pubertal stallions. Furthermore, lactoferrin binds to sperm, suggesting a
      biological role for protection or regulation of sperm in the corpus and cauda. In
      addition, estrogen appears to regulate lactoferrin secretion in the cauda of the
      epididymis in post-pubertal stallions.

PMID- 24856475
TI  - Inhibition of embryo implantation in mice through vaginal administration of a
      proprotein convertase 6 inhibitor.
AB  - Uterine proprotein convertase 6 (PC6) plays a critical role in embryo
      implantation in both mice and women. It was hypothesized that inhibiting uterine
      PC6 could prevent pregnancy. Vaginal administration of a PC6 inhibitor presents
      the ideal route for local drug delivery. A peptide-based PC6 inhibitor, C-30k-PEG
      Poly R that was previously shown to have properties of increased vaginal
      absorption and penetration was tested for its contraceptive potential in mice
      following vaginal administration. The study demonstrated that this approach could
      inhibit embryo implantation in some mice (24% completely and 47% partially
      inhibited).

PMID- 24856476
TI  - In vitro sperm maturation in sterlet, Acipenser ruthenus.
AB  - The aim of the study was to examine sperm maturation in sturgeon and to establish
      the localization of the maturation. We demonstrated that sperm maturation occurs
      in sturgeon outside the testes via dilution of sperm by urine. The process
      involves the participation of high molecular weight (>10kDa) substances and
      calcium ions.

PMID- 24856477
TI  - Novel phlebovirus with zoonotic potential isolated from ticks, Australia.
AB  - Recently discovered tick-borne phleboviruses have been associated with severe
      disease and death among persons in Asia and the United States. We report the
      discovery of a novel tick phlebovirus in Tasmania State, Australia, that is
      closely related to those zoonotic viruses found in Asia and North America. 

PMID- 24856478
TI  - Acquired idiopathic anhidrosis: a diagnosis often missed.
AB  - BACKGROUND: Acquired idiopathic anhidrosis (AIA) is an uncommon entity
      characterized by anhidrosis in the absence of any neurologic or sweat gland
      abnormalities. OBJECTIVE: The aim of this study was to characterize the clinical
      profile in a cohort of patients diagnosed with AIA at a tertiary dermatologic
      center. METHODS: We retrospectively evaluated cases seen during a 10-year period.
      Inclusion criteria included all cases of generalized or partial anhidrosis with
      no obvious causes, confirmed by provocative starch-iodine sweat test. Ectodermal
      dysplasias, poral dysfunction from chronic dermatoses, autonomic dysfunction, and
      drug-induced causes were excluded. RESULTS: Fifteen Chinese patients were
      diagnosed with AIA, mostly healthy young men with no significant medical or drug
      history, with variable extent of body surface area involvement. Serum
      immunoglobulin E, a complete blood cell count, thyroid function test, and
      antinuclear antibody levels were unremarkable. Anhidrotic areas revealed normal
      eccrine appendages with mild perivascular and perieccrine lymphocytic infiltrate.
      There were no neurologic abnormalities. LIMITATIONS: This was a retrospective
      study. CONCLUSION: Our study shows that AIA seems to be a heterogeneous group
      with no major dysfunction other than anhidrosis. Proper recognition and
      evaluation is paramount, especially for at-risk populations, so that appropriate
      measures on the prevention of heat injuries can be instituted.

PMID- 24856479
TI  - Bladder cancer: what we can do against this powerful enemy?

PMID- 24856480
TI  - Early stage prostate cancer: biochemical recurrence after treatment.
AB  - OBJECTIVES: To identify retrospectively through chart analysis the biochemical
      recurrence frequency of localized prostate cancer at diagnosis of patients
      submitted to surgery or radiotherapy; to correlate diagnostic characteristics
      associated with higher risk of biochemical recurrence. MATERIALS AND METHODS:
      Retrospective analysis of 483 patients treated in a single center, from March
      2000 to December 2009 in order to verify factors associated with biochemical
      recurrence. RESULTS: Biochemical recurrence was more frequent in patients with
      higher initial PSA levels and those with higher risk disease. Recurrence was more
      frequent in patients with high risk (25.9%) than those with intermediate risk
      (10.7%)) and low risk (5.5%). There was no significant statistical difference of
      biochemical recurrence between patients submitted to radiotherapy or radical
      prostatectomy. Biochemical recurrence was diagnosed in only 11 of 73 patients
      (15%)) submitted to conformal radiotherapy using tridimensional technique.
      CONCLUSION: Radiotherapy and radical prostatectomy have similar treatment
      results. Tridimensional conformal radiotherapy used nowadays is more efficient
      than earlier forms of radiation therapy (cobalt therapy and bidimensional linear
      accelerator therapy).

PMID- 24856481
TI  - Biochemical recurrence rates are similar for pT2-positive surgical margins and
      pT3a.
AB  - OBJECTIVE: Histological details of positive surgical margins in radical
      prostatectomy specimens have been related to outcome after surgery in rare
      studies recently published. Our objective is to assess whether the status of
      surgical margins, the extent and the Gleason score of positive margins, and the
      extent of the extraprostatic extension are predictive of biochemical recurrence
      post-radical prostatectomy. MATERIALS AND METHODS: Three hundred sixty-five
      radical prostatectomy specimens were analyzed. The length of the positive
      surgical margin and extraprostatic extension and the Gleason score of the margin
      were recorded. Statistical analyses examined the predictive value of these
      variables for biochemical recurrence. RESULTS: 236 patients were stage pT2R0, 58
      pT2R1, 25 pT3R0 and 46 pT3R1. Biochemical recurrence occurred in 11%, 31%, 20%
      and 45.7% of pT2R0, pT2R1, pT3R0 and pT3R1, respectively. The extent of the
      positive surgical margins and the Gleason score of the positive surgical margins
      were not associated with biochemical recurrence in univariate analysis in a mean
      follow up period of 35.9 months. In multivariate analyses, only the status of the
      surgical margins and the global Gleason score were associated with biochemical
      recurrence, with a risk of recurrence of 3.1 for positive surgical margins and of
      3.8 for a Gleason score > 7. CONCLUSION: Positive surgical margin and the global
      Gleason score are significant risk factors for biochemical recurrence post
      radical prostatectomy, regardless of the extent of the surgical margin, the
      extent of the extraprostatic extension, or the local Gleason score of the
      positive surgical margin or extraprostatic tissue. pT2R1 disease behaves as pT3R0
      and should be treated similarly.

PMID- 24856482
TI  - Is active surveillance a safe alternative in the management of localized prostate
      cancer? Pathological features of radical prostatectomy specimens in potential
      candidates for active surveillance.
AB  - INTRODUCTION AND OBJECTIVE: Active surveillance (AS) has become an accepted
      alternative for patients with low risk prostate cancer. The purpose of AS is to
      defer definitive therapy in these patients to avoid treatment-related
      complications. Our aim was to determine the pathological features of the surgical
      specimen from potential AS candidates that underwent radical prostatectomy (RP).
      MATERIALS AND METHODS: We retrospectively reviewed a group of patients submitted
      to RP who met criteria for AS: Gleason score (GS) <= 3+3 = 6, PSA <= 10ng/mL, T1c
      - T2a,< 1/3 of positive cores, < 50% of involvement in any core and PSA density <
      0.15. We determined the concordance between GS in biopsy and RP specimen (RPS).
      Other pathological features of the RPS were also analyzed, including surgical
      margins, extracapsular extension, seminal vesicles and lymph node involvement.
      RESULTS: We identified 167 patients subjected to RP that met the criteria for AS.
      Fifty two patients (31.1%) had a GS > 6 in the RPS (GS 7 n = 49; GS 8 n = 3).
      Extracapsular extension, seminal vesicle and lymph node involvement was found in
      6.1%, 3.1% and 1.2% of the specimens, respectively. CONCLUSION: In this study a
      significant proportion of potential candidates for AS showed features of
      aggressive and/or high-risk tumors in the RPS. Therefore, before considering a
      patient for an AS protocol, a proper and strict selection must be performed, and
      informed consent is crucial for these patients.

PMID- 24856483
TI  - External validation of a Brazilian predictive nomogram for pathologic outcomes
      following radical prostatectomy in tertiary teaching institutions: the USP
      nomograms.
AB  - PURPOSES: (a) To externally validate the Crippa and colleagues' nomograms
      combining PSA, percentage of positive biopsy cores (PPBC) and biopsy Gleason
      score to predict organ-confined disease (OCD) in a contemporary sample of
      patients treated at a tertiary teaching institution. (b) To adjust such
      variables, resulting in predictive nomograms for OCD and seminal vesicle invasion
      (SVI): the USP nomograms. MATERIALS AND METHODS: The accuracy of Crippa and
      colleagues' nomograms for OCD prediction was examined in 1002 men submitted to
      radical prostatectomy between 2005 and 2010 at the University of Sao Paulo (USP).
      ROC-derived area under the curve (AUC) and Brier scores were used to assess the
      discriminant properties of nomograms for OCD. Nomograms performance was explored
      graphically with LOESS smoothing plots. Furthermore, univariate analysis and
      logistic regression models targeted OCD and SVI. Variables consisted of PSA,
      PPBC, biopsy Gleason score and clinical stage. The resulted predictive nomograms
      for OCD and SVI were internally validated with bootstrapping and the same
      abovementioned procedures. RESULTS: Crippa and colleagues' nomograms for OCD
      showed ROC AUC = 0.68 (CI: 0.65-0.70), Brier score = 0.17 and overestimation in
      LOESS plots. USP nomograms for OCDand SVI showed ROC AUC of 0.73 (CI: 0.70-0.76)
      and 0.77 (CI: 0.73-0.79), respectively, and Brier scores of 0.16 and 0.08,
      respectively. The LOESS plots showed excellent calibration for OCD and
      underestimation for SVI. CONCLUSIONS: Crippa and colleagues' nomograms showed
      moderate discrimination and considerable OCD overestimation. USP nomograms showed
      good discrimination for OCD and SVI, as well as excellent calibration for OCD and
      SVI underestimation.

PMID- 24856484
TI  - Re-examination of the natural history of high-grade T1 bladder cancer using a
      large contemporary cohort.
AB  - INTRODUCTION: High-grade T1 (HGT1) bladder cancer represents a clinical challenge
      in that the urologist must balance the risk of disease progression against the
      morbidity and potential mortality of early radical cystectomy and urinary
      diversion. Using two non-muscle invasive bladder cancer (NMIBC) databases, we re
      examined the rate of progression of HG T1 bladder cancer in our bladder cancer
      populations. MATERIALS AND METHODS: We queried the NMIBC databases that have been
      established independently at the Atlanta Veterans Affairs Medical Center (AVAMC)
      and the University of Pennsylvania to identify patients initially diagnosed with
      HGT1 bladder cancer. Demographic, clinical, and pathologic variables were
      examined as well as rates of recurrence and progression. RESULTS: A total of 222
      patients were identified; 198 (89.1%) and 199 (89.6%) of whom were male and non
      African American, respectively. Mean patient age was 66.5 years. 191 (86.0%) of
      the patients presented with isolated HG T1 disease while 31 (14.0%) patients
      presented with HGT1 disease and CIS. Induction BCG was utilized in 175 (78.8%)
      patients. Recurrence occurred in 112 (50.5%) patients with progression occurring
      in only 19 (8.6%) patients. At a mean follow-up of 51 months, overall survival
      was 76.6%. Fifty two patients died, of whom only 13 (25%) patient deaths were
      bladder cancer related. CONCLUSIONS: In our large cohort of patients, we found
      that the risk of progression at approximately four years was only 8.6%. While
      limited by its retrospective nature, this study could potentially serve as a
      starting point in re-examining the treatment algorithm for patients with HG T1
      bladder cancer.

PMID- 24856486
TI  - Incidence and clinical characteristics of lower urinary tract symptoms as a
      presenting symptom for patients with newly diagnosed bladder cancer.
AB  - PURPOSE: The incidence of lower urinary tract symptoms (LUTS) as the sole
      presenting symptom for bladder cancer has traditionally been reported to be low.
      The objective of this study was to evaluate the prevalence and clinical
      characteristics of newly diagnosed bladder cancer patients who presented with
      LUTS in the absence of gross or microscopic hematuria. MATERIALS AND METHODS: We
      queried our database of bladder cancer patients at the Atlanta Veteran's Affairs
      Medical Center (AVAMC) to identify patients who presented solely with LUTS and
      were subsequently diagnosed with bladder cancer. Demographic, clinical, and
      pathologic variables were examined. RESULTS: 4.1% (14/340) of bladder cancer
      patients in our series presented solely with LUTS. Mean age and Charlson Co
      morbidity Index of these patients was 66.4 years (range = 52-83) and 3 (range = 0
      7), respectively. Of the 14 patients in our cohort presenting with LUTS, 9
      (64.3%), 4 (28.6%), and 1 (7.1%) patients presented with clinical stage Ta,
      carcinoma in Situ (CIS), and T2 disease. At a median follow-up of 3.79 years,
      recurrence occurred in 7 (50.0%) patients with progression occurring in 1 (7.1%)
      patient. 11 (78.6%) patients were alive and currently disease free, and 3 (21.4%)
      patients had died, with only one (7.1%) death attributable to bladder cancer.
      CONCLUSIONS: Our database shows a 4.1% incidence of LUTS as the sole presenting
      symptom in patients with newly diagnosed bladder cancer. This study suggests that
      urologists should have a low threshold for evaluating patients with unexplained
      LUTS for underlying bladder cancer.

PMID- 24856485
TI  - Lipiodol as a fiducial marker for image-guided radiation therapy for bladder
      cancer.
AB  - PURPOSE: To evaluate Lipiodol as a liquid, radio-opaque fiducial marker for image
      guided radiation therapy (IGRT) for bladder cancer. MATERIALS AND METHODS:
      Between 2011 and 2012, 5 clinical T2a-T3b N0 M0 stage II-III bladder cancer
      patients were treated with maximal transurethral resection of a bladder tumor
      (TURBT) and image-guided radiation therapy (IGRT) to 64.8 Gy in 36 fractions +/-
      concurrent weekly cisplatin-based or gemcitabine chemotherapy. Ten to 15mL
      Lipiodol, using 0.5mL per injection, was injected into bladder submucosa
      circumferentially around the entire periphery of the tumor bed immediately
      following maximal TURBT. The authors looked at inter-observer variability
      regarding the size and location of the tumor bed (CTVboost) on computed
      tomography scans with versus without Lipiodol. RESULTS: Median follow-up was 18
      months. Lipiodol was visible on every orthogonal two-dimensional kV portal image
      throughout the entire, 7-week course of IGRT. There was a trend towards improved
      inter-observer agreement on the CTVboost with Lipiodol (p = 0.06). In 2 of 5
      patients, the tumor bed based upon Lipiodol extended outside a planning target
      volume that would have been treated with a radiation boost based upon a
      cystoscopy report and an enhanced computed tomography (CT) scan for staging.
      There was no toxicity attributable to Lipiodol. CONCLUSIONS: Lipiodol constitutes
      a safe and effective fiducial marker that an urologist can use to demarcate a
      tumor bed immediately following maximal TURBT. Lipiodol decreases inter-observer
      variability in the definition of the extent and location of a tumor bed on a
      treatment planning CT scan for a radiation boost.

PMID- 24856487
TI  - Tubeless percutaneous nephrolithotomy: outcomes with expanded indications.
AB  - INTRODUCTION: Tubeless PCNL has been utilized to shorten hospital stay and
      improve patient postoperative pain control. Prior studies have excluded those
      patients with significant bleeding or other complications. Our objective was to
      evaluate the utility of tubeless PCNL in all patients irrespective of
      intraoperative outcome. MATERIALS AND METHODS: A retrospective review of the
      charts of patients who underwent PCNL at our institute was performed. Patients
      were assigned to one endourologist Who routinely performed tubeless PCNL and to a
      second endourologist who routinely left a small-bore pigtail nephrostomy.
      Preoperative demographics operative and postoperative outcomes were compared.
      RESULTS: Out of 159 patients included, 83 patients had tubeless PCNL while 76
      patients had standard PCNL. There was no difference between groups regarding age,
      gender, ASA score, number, maximum diameter of stones, number of calyces
      involved, Stone density (HU), laterality and use of preoperative narcotics. While
      staghorn stones were more common in patients who underwent standard PCNL (p =
      0.008). Tubeless patients had less number of access tracts (p <= 0.001), shorter
      hospital stay (1.7 vs. 3.0 days, p = 0.001) when compared to standard PCNL group.
      Multivariable analysis controlling for confounding factors including staghorn
      calculi and number of accesses confirmed that tubeless PCNL was associated with
      shorter hospital stay and less postoperative pain. There was no significant
      difference in complication rates between the two groups. CONCLUSION: Our report
      confirms the previous reports of shorter hospital stay, less pain and analgesia
      as compared to standard PCNL, and establishes its safety irrespective of
      bleeding, perforation, extravasation or other intraoperative issues that have
      previously been utilized as exclusionary criteria for this approach.

PMID- 24856488
TI  - The skin-to-calyx distance measured by renal ct scan and ultrasound.
AB  - PURPOSE: We developed a stereotactic device to guide the puncture for
      percutaneous nephrolithotripsy, which uses the distance from the target calyx to
      its perpendicular point on skin (SCD) to calculate the needle's entry angle. This
      study seeks to validate the use of measurements obtained by ultrasound (US) and
      computerized tomography (CT) for needle's entry angle calculation and to study
      factors that may interfere in this procedure. MATERIALS AND METHODS: Height,
      weight, abdominal circumference, CT of the urinary tract in dorsal decubitus (DD)
      and ventral decubitus (VD), and US of the kidneys in VD were obtained from thirty
      five renal calculi patients. SCD obtained were compared and correlated with body
      mass index (BMI). RESULTS: BMI was 28.66 +/- 4.6 Kg/m2. SCD on CT in DD was 8.40
      +/- 2.06cm, in VD was 8.32 +/- 1.95cm, in US was 6.74 +/- 1.68cm. SCD measured by
      US and CT were statistically different (p < 0.001), whereas between CT in DD and
      VD were not. SCD of the lower calyx presented moderate correlation with BMI.
      CONCLUSION: SCD obtained by CT in ventral and dorsal decubitus may be used for
      calculation of the needle's entry angle. SCD obtained by US cannot be used. A
      rule for the correlation between BMI and the SCD could not be determined.

PMID- 24856489
TI  - Application of self-retaining bidirectional barbed absorbable suture in
      retroperito- neoscopic partial nephrectomy.
AB  - OBJECTIVE: To investigate the safety and feasibility of self-retaining
      bidirectional barbed absorbable suture application in retroperitoneoscopic
      partial nephrectomy. MATERIALS AND METHODS: From Sep 2011 and Aug 2012, 76 cases
      of retroperitoneoscopic partial nephrectomy were performed at our hospital. The
      patients were divided into two groups: self-retaining barbed suture (SRBS) group
      (n = 36) and non-SRBS group (n = 40). There was no significant difference in age,
      sex, tumor size and location between the two groups. Clinical data and outcomes
      were analyzed retrospectively. RESULTS: All 76 cases of retroperitoneoscopic
      partial nephrectomy were successfully performed, without conversion to open
      surgery or serious intraoperative complications. In the SRBS group, the suture
      time, warm ischemia time and operation blood loss were significantly shorter than
      that of non-SRBS group (p < 0.01), and operation time and hospital stay were
      shorter than that of non-SRBS group (p < 0.05). CONCLUSIONS: The application of
      self-retaining bidirectional barbed absorbable suture in retroperitoneoscopic
      partial nephrectomy could shorten suture time and warm ischemia time, with good
      safety and feasibility, worthy of being used in clinic.

PMID- 24856490
TI  - A single-institution experience with metallic ureteral stents: a cost-effective
      method of managing deficiencies in ureteral drainage.
AB  - INTRODUCTION: The limitations of traditional ureteral stents in patients with
      deficiencies in ureteral drainage have resulted in frequent stent exchanges. The
      implementation of metallic stents was introduced to improve the patency rates of
      patients with chronic upper urinary tract obstruction, obviating the need for
      frequent stent exchanges. We report our clinical experiences with the use of
      metallic ureteral stents in the management of poor ureteral drainage. MATERIALS
      AND METHODS: Fifty patients underwent metallic ureteral stent placement from 2009
      to 2012. Stent failure was defined as an unplanned stent exchange, need for
      nephrostomy tube placement, increasing hydronephrosis with stent in place, or an
      elevation in serum creatinine. Stent life was analyzed using the Kaplan-Meier
      methodology, as this was a time dependent continuous variable. A cost analysis
      was similarly conducted. RESULTS: A total of 97 metallic stents were placed among
      our cohort of patients: 63 in cases of malignant obstruction, 33 in the setting
      of cutaneous ureterostomies, and 1 in an ileal conduit urinary diversion.
      Overall, stent failure occurred in 8.2% of the stents placed. Median stent life
      was 288.4 days (95% CI: 277.4-321.2 days). The estimated annual cost for
      traditional polymer stents (exchanged every 90 days) was $9,648-$13,128, while
      the estimated cost for metallic stents was $4,211-$5,313. CONCLUSION: Our results
      indicate that metallic ureteral stent placement is a technically feasible
      procedure with minimal complications and is well tolerated among patients.
      Metallic stents can be left in situ for longer durations and provide a
      significant financial benefit when compared to traditional polymer stents.

PMID- 24856491
TI  - The comparison of urodynamic findings in women with various types of urinary
      incontinence.
AB  - PURPOSE: We aimed to determine the differences of the urodynamic findings of mix
      urinary incontinence (MUI), urge urinary incontinence (UUI), and stress urinary
      incontinence (SUI), and to evaluate the urodynamic findings in different groups
      by using bladder sensitivity index (BSI). MATERIALS AND METHODS: The data of 99
      patients who underwent urodynamic testing related to the suspicion of SUI, UUI or
      MUI were analysed. This analysis included a retrospective evaluation of patients'
      cards, voiding diaries, and urodynamic reports. At filling cystometry, the
      parameters of first sensation of bladder filling (FSBF), first desire to void
      (FDV), strong desire to void (SDV), and bladder capacity (Vmax), which were
      related to the bladder sensation, were determined. Subsequently, uroflowmetric
      findings were recorded during bladder emptying. BSI was defined as the ratio of
      Vmax/ FDV. These results were statistically compared among the goups. RESULTS:
      The sample included 35(35.5%) MUI, 33(33.3%) UUI and 31 (31.1%) SUI. The mean
      ages were similar in all groups (P = 0.868). The mean FSBF, FDV, SDV and Vmax
      values were significantly different among groups (p = 0.004, p < 0.001, p <
      0.001, p < 0.001 respectively). Nevertheless, there was no statistically
      significant difference among the mean daily voiding accounts (P = 0.005).
      Although the mean maximum flow rate (Qmax) values were similar (P = 0.428), the
      mean maximum detrusor pressure (Pdet(max)) values were significantly different (P
      = 0.021). The mean BSI values showed no significant differences (P = 0.097).
      CONCLUSIONS: It was concluded that while the use of urodynamic testing could
      contribute to the management of urinary incontinence, the indexes including BSI
      requere more detailed and comprehensive studies.

PMID- 24856492
TI  - Obesity may influence the relationship between sex hormones and lower urinary
      tract symptoms.
AB  - PURPOSE: The effects of serum testosterone in the lower urinary tract symptoms
      (LUTS) in patients with benign prostatic hyperplasia (BPH) are not well
      established. The objective of the study is to evaluate the association of sex
      hormones with LUTS and control the results by patient weight. MATERIALS AND
      METHODS: The study comprised a cross-sectional analysis of 725 men included in a
      prostate cancer screening program at University of Sao Paulo Medical School. The
      serum concentrations of total testosterone (TT), free testosterone (FT) and sex
      hormone binding globulin (SHBG) were measured. Variables analyzed were age,
      American Urological Association (AUA) symptom score, storage symptoms, voiding
      symptoms, quality of life score, prostate specific antigen levels and prostate
      volume. Obesity was measured through the calculation of body mass index (BMI). A
      regression analysis model was performed. RESULTS: Median patient age was 65 years
      (48 to 94). A higher TT level was significantly associated with a severe AUA
      symptom score only among patients with a BMI >= 25. Median TT was 371, 370 and
      427ng/dL (p = 0.017) in patients with mild, moderate and severe LUTS
      respectively. The multivariate regression analysis in patients with BMI >= 25
      showed that only age, TT and sex score were related to LUTS. CONCLUSIONS: A
      higher TT is associated with a severe AUA score symptom index only in obese
      patients. Further analysis are necessary to evaluate the mechanisms through which
      testosterone may influence LUTS in these patients.

PMID- 24856493
TI  - Human papillomavirus infection is not related with prostatitis-related symptoms:
      results from a case-control study.
AB  - PURPOSE: To investigate the relationship between human papillomavirus (HPV)
      infection and prostatitis-related symptoms. MATERIALS AND METHODS: All young
      heterosexual patients with prostatitis-related symptoms attending the same Center
      from January 2005 to December 2010 were eligible for this case-control study.
      Sexually active asymptomatic men were considered as the control group. All
      subjects underwent clinical examination, Meares-Stamey test and DNA-HPV test.
      Patients with prostatitis-related symptoms and asymptomatic men were compared in
      terms of HPV prevalence. Moreover, multivariable Cox proportional hazards
      regression analysis was performed to determine the association between HPV
      infection and prostatitis-related symptoms. RESULTS: Overall, 814 out of 2,938
      patients (27.7%) and 292 out of 1,081 controls (27.0%) proved positive to HPV.
      The HPV genotype distribution was as follows: HR-HPV 478 (43.3%), PHR-HPV 77
      (6.9%), LR-HPV 187 (16.9%) and PNG-HPV 364 (32.9%). The most common HPV genotypes
      were: 6, 11, 16, 26, 51, 53 and 81. No difference was found between the two
      groups in terms of HPV infection (OR 1.03; 95% CI 0.88-1.22; p = 0.66). We noted
      a statistically significant increase in HPV infection over the period 2005 to
      2010 (p < 0.001) in both groups. Moreover, we found a statistically significant
      increase in HPV 16 frequency from 2005 to 2010 (p = 0.002). CONCLUSIONS: This
      study highlights that prostatitis-like symptoms are unrelated to HPV infection.
      Secondary, we highlight the high prevalence of asymptomatic HPV infection among
      young heterosexual men.

PMID- 24856494
TI  - Qualitative analysis of the deposit of collagen in bladder suture of rats treated
      with tacrolimus combined with mycophenolate-mofetil.
AB  - PURPOSE: To evaluate the synthesis of type I (mature) and type III (immature)
      collagen in bladder suture of rats treated with a combination of tacrolimus and
      mycophenolate mofetil for 15 days. MATERIALS AND METHODS: Thirty rats were
      divided into 3 groups: the sham, control and experimental groups. All the animals
      underwent laparotomy, cystotomy and bladder suture in two planes with surgical
      PDS 5-0 thread. The sham group did not receive treatment. The control group
      received saline solution, and the experimental group received 0.1mg/kg/day of
      tacrolimus with 20mg/kg/day of mycophenolate mofetil, for 15 days. From then on,
      the tacrolimus was dosed. The surgical specimens of the bladder suture area were
      processed so that the total type I and type III collagen could be measured by the
      picrosirius red technique. RESULTS: There was a predominance of type I collagen
      production in the sham and control groups compared to the experimental group, in
      which type III collagen was predominant. The production of total collagen did not
      change. CONCLUSION: The association of tacrolimus and mycophenolate mofetil in
      animals qualitatively changes the production of collagen after 15 days with a
      predominance of type III collagen.

PMID- 24856495
TI  - Pure conventional laparoscopic radical nephrectomy with level II vena cava tumor
      thrombectomy.
AB  - The surgical management with laparoscopic technique for renal cell carcinoma with
      inferior vena cava tumor thrombus (IVTT) remains challenging and technically
      demanding in urological oncology. We present two patients with level II IVTT that
      were managed with pure conventional laparoscopic radical nephrectomy and
      thrombectomy. Two patients were diagnosed with a renal tumor with level II IVTT
      from December 2011 to January 2012. They both underwent pure conventional
      laparoscopic radical nephrectomy with thrombectomy. During these operations,
      intraoperative laparoscopic ultrasonography was used to detect the thrombus and
      ensure complete removal. Two patients were operated through retroperitoneal
      approach for right renal tumor and transperitoneal approach for left renal tumor
      respectively. The demographics, perioperative and follow-up data were recorded
      for the study. Both operations were successfully performed without conversion.
      They both had no radiographic evidence of recurrence during follow-up. It is
      concluded that it is feasible to manage renal cell carcinoma with level II IVTT
      through pure conventional laparoscopic approach in carefully selected patients,
      which might expand the indication for laparoscopic surgery. The pure laparoscopic
      approach in the treatment of renal cell carcinoma with level II vena cava tumor
      thrombus is challenging and requires advanced laparoscopic skills. Multicenter
      prospective randomized control trials are needed to prove the benefits of this
      approach.

PMID- 24856496
TI  - Urothelial carcinoma in a pyelocaliceal diverticulum discovered by magnetic
      resonance urography.
AB  - Neither computed tomography (CT) nor intravenous pyelography (IVP) alone can
      diagnose tumors of renal pelvic diverticula, but magnetic resonance urography
      (MRU) can obtain accurate preoperative information.

PMID- 24856497
TI  - Fracture of corpora cavernosa with massive cavernosal-venous shunts.

PMID- 24856499
TI  - Laparoscopic bladder diverticulectomy assisted by cystoscopic transillumination.

PMID- 24856498
TI  - Robot assisted laparoscopic excision of a paraganglioma: new therapeutic
      approach.
AB  - The Paraganglioma is the most common extra-adrenal pheochromocytoma arising from
      neural crest (1) (It will better to write: The paraganglioma is an extra-adrenal
      pheocromocytoma arising from the neural crest. 10% of pheocromocytomas are extra
      adrenal and can arise form chromaffin tissue derived from primitive
      neuroectoderm). Minimally invasive techniques allow surgeons to perform the
      procedure without wide exposure and mobilization of intra abdominal organs. To
      our knowledge we present the third case of robotic excision of a retroperitoneal
      paraganglioma.

PMID- 24856500
TI  - Transluminal approaches to vesicorectal fistula repair.

PMID- 24856501
TI  - Re: PGC and PSMA in prostate cancer diagnosis: tissue analysis from biopsy
      samples.

PMID- 24856502
TI  - Re: A review of continuous vs intermittent androgen deprivation therapy:
      redefining the gold standard in the treatment of advanced prostate cancer. Myths,
      facts and new data on a "perpetual dispute".

PMID- 24856503
TI  - Re: Long-term results of permanent memotherm urethral stent in the treatment of
      recurrent bulbar urethral strictures.

PMID- 24856505
TI  - Factors related to online patient satisfaction with ophthalmologists.

PMID- 24856504
TI  - Prognostic significance of the epithelial-to-mesenchymal transition markers e
      cadherin, vimentin and twist in bladder cancer.
AB  - OBJECTIVE: The goal of this study was to utilize long-term patient follow-up to
      determine whether epithelial-to-mesenchymal transition (EMT)-related markers can
      predict bladder cancer patient survival and progression of disease. MATERIALS AND
      METHODS: This study included 121 patients with bladder cancer. Sixty-four of
      these patients presented with non-muscle invasive (NMI, stage T1) bladder cancer
      and 57 with muscle invasive (MI, stage T2, T3). The patients were diagnosed and
      treated between May 1998 and July 2012. The EMT markers E-cadherin, Twist, and
      Vimentin were detected via immunohistochemistry. Univariate and multivariate/Cox
      analyses were then utilized to determine whether these EMT markers could be
      useful prognostic markers for predicting bladder cancer patient outcomes.
      RESULTS: Analysis of the 121 bladder cancer patients in this study revealed that
      the frequency of E-cadherin expression was 59.5% (72/121), Twist was 54.5%
      (66/121), and Vimentin was 24.8% (30/121). Twist and Vimentin were found to have
      statistically significant correlations with grade, recurrence, and progression
      but not with stage, whereas E-cadherin was associated with stage but not with the
      other parameters. In the univariate analysis, grade (p = 0.02) was the only
      significant predictor for progression-free survival (PFS). Stage, grade, and
      expression of E-cadherin, Vimentin and Twist were included in the multivariate
      analysis of predicting PFS. In this analysis, grade (p = 0.01) and Vimentin
      expression (p = 0.001) were found to be significant prognostic factors in
      predicting PFS. CONCLUSIONS: Grade and Vimentin are potential independent
      indicators in predicting bladder cancer progression and survival.

PMID- 24856506
TI  - Carbon nanotube and carbon nanorod-filled polyacrylonitrile electrospun
      stationary phase for ultrathin layer chromatography.
AB  - The application of carbon nanotube or nanorod/polyacrylonitrile (PAN) composite
      electrospun nanofibrous stationary phase for ultrathin layer chromatography
      (UTLC) is described herein. Multi-walled carbon nanotubes (MWCNTs) and edge-plane
      carbon (EPC) nanorods were prepared and electrospun with the PAN polymer solution
      to form composite nanofibers for use as a UTLC stationary phase. The analysis of
      laser dyes demonstrated the feasibility of utilizing carbon nanoparticle-filled
      electrospun nanofibers as a UTLC stationary phase. The contribution of MWCNT or
      EPC in changing selectivity of the stationary phase was studied by comparing the
      chromatographic behavior among MWCNT-PAN plates, EPC-PAN plates and pure PAN
      plates. Carbon nanoparticles in the stationary phase were able to establish
      strong pi-pi interactions with aromatic analytes. The separation of five
      polycyclic aromatic hydrocarbons (PAHs) demonstrated enhanced chromatographic
      performance of MWCNT-filled stationary phase by displaying substantially improved
      resolution and separation efficiency. Band broadening of the spots for MWCNT or
      EPC-filled UTLC stationary phases was also investigated and compared with that
      for pure PAN stationary phases. A 50% improvement in band dispersion was noted
      using the MWCNT based composite nanofibrous UTLC plates. 

PMID- 24856507
TI  - An appropriate and systematized procedure for validating qualitative methods: its
      application in the detection of sulfonamide residues in raw milk.
AB  - The lack of well-established references for the validation of qualitative
      analyses and the increasing demand for reliable binary responses were the main
      motivating factors for this study. A detailed procedure for single-laboratory
      validation of qualitative methods is proposed. The experimental design and the
      tools for data analysis were based on the theoretical background, as well as the
      aspects of efficiency, convenience and simplicity. Four experimental steps were
      defined, as follows: (i) preliminary tests for the determination of the
      concentration range, (ii) a study of the rates, unreliability region, detection
      limit, and the accordance and concordance values, (iii) a study of the
      selectivity in the presence of known interferences, and (iv) a study of
      robustness. The applicability of the procedure was demonstrated by the validation
      of a qualitative commercial kit for detecting sulfonamide residues in raw milk
      using both the visual and instrumental reading techniques. Reliability rates of
      100% were obtained for the blank samples. For the samples spiked with
      sulfamethazine at 10.8 and 108 MUg L(-1) and with sulfadimethoxine or
      sulfathiazole at 10 and 100 MUg L(-1), the reliability rates ranged from 93.3 to
      100%. Selectivity was demonstrated using trimethoprim as a potential interferent.
      The method was considered robust for the factors of the temperature (54 and 58
      degrees C) and time (6 and 10 min) for incubating the test strips. The estimated
      detection limits and unreliability regions confirmed the suitability of the kit
      for this purpose, based on the legislated residue limits.

PMID- 24856509
TI  - Experimental validation of an effective carbon number-based approach for the gas
      chromatography-mass spectrometry quantification of 'compounds lacking authentic
      standards or surrogates'.
AB  - For the quantitative analysis of 'compounds lacking authentic standards or
      surrogates' (CLASS) in environmental media, we previously introduced an effective
      carbon number (ECN) approach to develop an empirical equation for the prediction
      of their response factor (RF). In this research, a series of laboratory
      experiments were carried out to benchmark the reliability of an ECN approach for
      sorbent tube/thermal desorption/gas chromatography (GC)/mass spectrometry (MS)
      applications. First, the ECN values were determined using external calibration
      data from 25 reference volatile organic compounds (VOCs) using two MS dectectors
      (quadrupole (Q) and time-of-flight (TOF)). Then, a certified standard mixture of
      54 VOCs was analyzed by each system as a simulated unknown sample. The analytical
      bias, assessed in terms of percentage difference (PD) between the certified and
      ECN-predicted mass values, averaged 19.2+/-16.1% (TOF-MS) and 28.2+/-27.6% (Q
      MS). The bias using a more simplified carbon number (CN)-based prediction
      increased considerably, yielding 53.4+/-53.3% (TOF-MS) and 61.7+/-81.3% (Q-MS).
      However, the bias obtained using the ECN-based prediction decreased significantly
      to yield average PD values of 9.84+/-7.28% (TOF-MS) and 16.8+/-8.35% (Q-MS), if
      the comparison was limited to 26 (out of 54) VOCs with CN>=4 (i.e., 25 aromatics
      and hexachlorobutadiene). 

PMID- 24856508
TI  - Investigation of protein FTT1103 electroactivity using carbon and mercury
      electrodes. Surface-inhibition approach for disulfide oxidoreductases using
      silver amalgam powder.
AB  - Recently, it was shown that electrochemical methods can be used for analysis of
      poorly water-soluble proteins and for study of their structural changes and
      intermolecular (protein-ligand) interactions. In this study, we focused on
      complex electrochemical investigation of recombinant protein FTT1103, a disulfide
      oxidoreductase with structural similarity to well described DsbA proteins. This
      thioredoxin-like periplasmic lipoprotein plays an important role in virulence of
      bacteria Francisella tularensis. For electrochemical analyses, adsorptive
      transfer (ex situ) square-wave voltammetry with pyrolytic graphite electrode, and
      alternating-current voltammetry and constant-current chronopotentiometric
      stripping analysis with mercury electrodes, including silver solid amalgam
      electrode (AgSAE) were used. AgSAE was used in poorly water-soluble protein
      analysis for the first time. In addition to basic redox, electrocatalytic and
      adsorption/desorption characterization of FTT1103, electrochemical methods were
      also used for sensitive determination of the protein at nanomolar level and study
      of its interaction with surface of AgSA microparticles. Proposed electrochemical
      protocol and AgSA surface-inhibition approach presented here could be used in
      future for biochemical studies focused on proteins associated with membranes as
      well as on those with disulfide oxidoreductase activity. 

PMID- 24856510
TI  - Gold nanocatalyst-based immunosensing strategy accompanying catalytic reduction
      of 4-nitrophenol for sensitive monitoring of chloramphenicol residue.
AB  - A new competitive-type immunosensing system based on gold nanoparticles toward
      catalytic reduction of 4-nitrophenol (4-NP) was developed for sensitive
      monitoring of antibiotic residue (chloramphenicol, CAP, used in this case) by
      using ultraviolet-visible (UV-vis) spectrometry. Gold nanoparticle (AuNP) with 16
      nm in diameter was initially synthesized and functionalized with CAP-bovine serum
      albumin (CAP-BSA) conjugate, which were used as the competitor on monoclonal anti
      CAP antibody-coated polystyrene microtiter plate (MTP). In the presence of target
      CAP, the labeled CAP-BSA on the AuNP competed with target CAP for the immobilized
      antibody on the MTP. The conjugated amount of CAP-BSA-AuNP on the MTP decreased
      with the increase of target CAP in the sample. Upon addition of 4-NP and NaBH4
      into the MTP, the carried AuNP could catalytically reduce 4-NP to 4-aminophenol
      (4-AP), and the as-produced 4-AP could be monitored by using UV-vis absorption
      spectroscopy. Experimental results indicated that the absorbance at 403 nm
      increased with the increment of target CAP concentration in the sample, and
      exhibited a dynamic range from 0.1 to 100 ng mL(-1) with a detection limit (LOD)
      of 0.03 ng mL(-1) at the 3s(blank) level. Intra- and inter-assay coefficients of
      variation were lower than 5.5% and 8.0%, respectively. In addition, the
      methodology was evaluated for CAP spiked honey and milk samples, respectively.
      The recovery was 92-112%.

PMID- 24856511
TI  - Chiral metal-organic framework used as stationary phases for capillary
      electrochromatography.
AB  - Metal-organic frameworks (MOFs) have received great attention as novel media in
      separation sciences because of their fascinating structures and unusual
      properties. However, to the best of our knowledge, there has been no attempt to
      utilize chiral MOFs as stationary phases in capillary electrochromatography
      (CEC). In this study, a homochiral helical MOF [Zn2(D-Cam)2(4,4'-bpy)]n (D-Cam=D
      (+)-camphoric acid, 4,4'-bpy=4,4'-bipyridine) was explored as the chiral
      stationary phase in open tubular capillary electrochromatography (OT-CEC) for
      separation of chiral compounds and isomers. The MOFs coated column has been
      developed using a simple procedure via MOFs post-coated on the sodium silicate
      layer. The baseline separations of flavanone and praziquantel were achieved on
      the MOFs coated column with high resolution of more than 2.10. The influences of
      pH, organic modifier content and buffer concentration on separation were
      investigated. Besides, the separations of isomers (nitrophenols and ionones) were
      evaluated. The relative standard deviations (RSDs) for the retention time of run
      to-run, day-to-day and column-to-column were 1.04%, 2.16% and 3.07%,
      respectively. The results demonstrated that chiral MOFs are promising for
      enantioseparation in CEC. 

PMID- 24856512
TI  - Cardiac molecular markers of programmed cell death are activated in end-stage
      heart failure patients supported by left ventricular assist device.
AB  - BACKGROUND: Cardiomyocyte apoptosis increases in heart failure (HF) and is
      implicated in disease progression. The apoptotic cell is not inevitably committed
      to death, and appropriate therapy like left ventricular assist device (LVAD)
      support could offer a rescue of cellular functions. Literature data regarding the
      modulation of the apoptotic process during LVAD support are still controversial.
      METHODS: To assess whether LVAD implantation modifies the apoptotic profile in
      the heart, cardiac tissue was collected from end-stage HF patients before LVAD
      implant (pre-LVAD, n=22) and at LVAD removal (post-LVAD, n=6) and from stable HF
      patients on medical therapy without prior circulatory support (HTx, n=7) at heart
      transplantation as control. Caspase (Casp)-3, Bax, Bcl-2, and Hsp72 cardiac mRNA
      and protein expression were evaluated by real-time polymerase chain reaction and
      Western blotting (WB) in the three groups of patients. Immunohistochemical
      analysis, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling
      assay, and DNA laddering analysis were performed; cellular size and interstitial
      fibrosis content were also determined. RESULTS: All the apoptotic indices were
      increased in the post-LVAD group compared to pre-LVAD, specially antiapoptotic
      Hsp72 and proapoptotic Bax (Hsp72: 3.27+/-0.41 vs. 0.76+/-0.14, P<.001; Bax:
      2.15+/-0.38 vs. 1.10 +/- 0.29, P=.035; post-LVAD vs. pre-LVAD, respectively). The
      significant increase in Hsp72 was confirmed by WB and immunohistochemical
      analysis. CONCLUSION: LVAD appears to induce an activation of apoptotic
      mediators, mainly at the mitochondrial level, while the following activation of
      Casp-3 is reduced by the significant increase of Hsp72, whose enhancement could
      be an important factor in cardiac remodeling associated with LVAD support.

PMID- 24856513
TI  - DMRT1 protects male gonadal cells from retinoid-dependent sexual
      transdifferentiation.
AB  - Mammalian sex determination initiates in the fetal gonad with specification of
      bipotential precursor cells into male Sertoli cells or female granulosa cells.
      This choice was long presumed to be irreversible, but genetic analysis in the
      mouse recently revealed that sexual fates must be maintained throughout life.
      Somatic cells in the testis or ovary, even in adults, can be induced to
      transdifferentiate to their opposite-sex equivalents by loss of a single
      transcription factor, DMRT1 in the testis or FOXL2 in the ovary. Here, we
      investigate what mechanism DMRT1 prevents from triggering transdifferentiation.
      We find that DMRT1 blocks testicular retinoic acid (RA) signaling from activating
      genes normally involved in female sex determination and ovarian development and
      show that inappropriate activation of these genes can drive sexual
      transdifferentiation. By preventing activation of potential feminizing genes,
      DMRT1 allows Sertoli cells to participate in RA signaling, which is essential for
      reproduction, without being sexually reprogrammed.

PMID- 24856515
TI  - Differentiation between benign phyllodes tumors and fibroadenomas of the breast
      on MR imaging.
AB  - PURPOSE: The purpose of this study was to determine the factors that contribute
      to the differentiation between phyllodes tumors (PTs) and fibroadenomas (FAs) on
      MR imaging. MATERIALS AND METHODS: This retrospective study included 19 PTs and
      18 FAs with >= 2 cm diameter. The presence or absence of a capsule and internal
      septum, the extent of lobulation, and the apparent diffusion coefficient (ADC)
      values were determined. The presence or absence of a cystic component, the time
      intensity curve, and the signal intensity on delayed-phase contrast-enhanced T1WI
      were also evaluated in 31 patients (16 PTs and 17 FAs) who underwent a contrast
      enhanced study. RESULTS: Cystic components were seen in 10 of the 16 PTs (63%)
      and in 4 of the 17 FAs (24%; P=0.03). The PTs showed strong lobulation more
      frequently compared to the FAs (14/19 [74%] vs. 7/18 [39%], respectively;
      P=0.04). Though there was no significant difference, PT tended to be
      heterogeneous more frequently on the delayed phase of the contrast-enhanced T1WI
      compared to the FA (11/16 [69%] vs. 7/17 [41%], respectively). No significant
      difference was found in the other findings. CONCLUSIONS: Although PTs and FAs
      show similar MR findings, the presence of a cystic component, strong lobulation,
      and heterogeneity on delayed-phase contrast-enhanced T1WI suggests a PT.

PMID- 24856517
TI  - Physicochemical descriptors of aromatic character and their use in drug
      discovery.
AB  - Published physicochemical descriptors of molecules that convey aromaticity
      related character are reviewed in the context of drug design and discovery.
      Studies that have employed aromatic descriptors are discussed, and several
      descriptors are compared and contrasted. 

PMID- 24856514
TI  - VARP is recruited on to endosomes by direct interaction with retromer, where
      together they function in export to the cell surface.
AB  - VARP is a Rab32/38 effector that also binds to the endosomal/lysosomal R-SNARE
      VAMP7. VARP binding regulates VAMP7 participation in SNARE complex formation and
      can therefore influence VAMP7-mediated membrane fusion events. Mutant versions of
      VARP that cannot bind Rab32:GTP, designed on the basis of the VARP ankyrin
      repeat/Rab32:GTP complex structure described here, unexpectedly retain endosomal
      localization, showing that VARP recruitment is not dependent on Rab32 binding. We
      show that recruitment of VARP to the endosomal membrane is mediated by its direct
      interaction with VPS29, a subunit of the retromer complex, which is involved in
      trafficking from endosomes to the TGN and the cell surface. Transport of GLUT1
      from endosomes to the cell surface requires VARP, VPS29, and VAMP7 and depends on
      the direct interaction between VPS29 and VARP. Finally, we propose that endocytic
      cycling of VAMP7 depends on its interaction with VARP and, consequently, also on
      retromer. 

PMID- 24856516
TI  - Small part ultrasound in childhood and adolescence.
AB  - Small-part sonography refers to the display of small, near-surface structures
      using high-frequency linear array transducers. Traditional applications for small
      part ultrasound imaging include visualization and differential diagnostic
      evaluation in unclear superficial bodily structures with solid, liquid and mixed
      texture, as well as similar structures in nearly superficial organs such as the
      thyroid glands and the testes. Furthermore indications in the head and neck
      regions are the assessment of the outer CSF spaces in infants, the sonography of
      the orbit, the sonography of the walls of the large neck vessels, the
      visualization of superficially situated lymph nodes and neoplasms. Clinical
      evidence concludes that sonography, having of all imaging modalities the highest
      spatial resolution in the millimeter- and micrometer range (100-1000MUm), can be
      considered the best suited technique for examining superficial pathological
      formations and near-surface organs. In addition, it delivers important
      information about characteristic, often pathognomonic tissue architecture in
      pathological processes. 

PMID- 24856518
TI  - [Survey of antibiotic prescriptions in a Senegalese pediatric hospital].

PMID- 24856524
TI  - Infections in patients with cystic fibrosis: diagnostic microbiology update.
AB  - Survival has improved in patients with cystic fibrosis (CF), in part because of
      aggressive antimicrobial management. Two multidrug-resistant environmental
      bacteria, the Burkholderia cepacia group and nontuberculous mycobacteria, have
      emerged. Improving genomic and proteomic technologies are allowing better
      identification of bacteria and fungi found in the CF lung and detection of viral
      agents that may be associated with pulmonary exacerbations. Anaerobic bacteria
      and Streptococcus angionsus group organisms may play a role in chronic CF lung
      infections. The diversity of organisms declines perhaps as a result of aggressive
      antimicrobial therapy, and an apex predator, Pseudomonas aeruginosa, may emerge
      in many patients with CF. 

PMID- 24856525
TI  - Urine antigen tests for the diagnosis of respiratory infections: legionellosis,
      histoplasmosis, pneumococcal pneumonia.
AB  - Urinary antigen testing has grown in popularity for several significant
      respiratory infections, particularly Legionella pneumophila, Streptococcus
      pneumoniae, and Histoplasma capsulatum. By capitalizing on the concentration of
      shed antigen from a variety of pathogens in the kidneys for excretion in the
      urine, urinary antigen testing can be used to obtain rapid test results related
      to respiratory infection, independent of an invasive collection such as a
      bronchoalveolar lavage. This article describes the 3 aforementioned organisms,
      their role in respiratory disease, and the current status of urinary antigen
      testing in their respective diagnosis. 

PMID- 24856526
TI  - Pertussis: relevant species and diagnostic update.
AB  - Pertussis is increasing due to multiple factors including increasing awareness by
      clinicians, decreased effectiveness of vaccines, and improved testing. While
      Bordetella pertussis is the causative agent of pertussis other Bordetella species
      such as B. parapertussis, and B. holmesii, have been associated with pertussis
      like illness. Laboratory diagnosis is made using various tests with molecular
      methods supplanting culture due to increased sensitivity. Serology is useful but
      standardized methods that are needed. The targets used for molecular detection
      are varied and have differing sensitivities and specificities. Laboratorians must
      consider if differentiation of various Bordetella species is necessary when
      choosing an amplified testing approach. 

PMID- 24856523
TI  - Bats as reservoir hosts of human bacterial pathogen, Bartonella mayotimonensis.
AB  - A plethora of pathogenic viruses colonize bats. However, bat bacterial flora and
      its zoonotic threat remain ill defined. In a study initially conducted as a
      quantitative metagenomic analysis of the fecal bacterial flora of the Daubenton's
      bat in Finland, we unexpectedly detected DNA of several hemotrophic and
      ectoparasite-transmitted bacterial genera, including Bartonella. Bartonella spp.
      also were either detected or isolated from the peripheral blood of Daubenton's,
      northern, and whiskered bats and were detected in the ectoparasites of
      Daubenton's, northern, and Brandt's bats. The blood isolates belong to the
      Candidatus-status species B. mayotimonensis, a recently identified etiologic
      agent of endocarditis in humans, and a new Bartonella species (B. naantaliensis
      sp. nov.). Phylogenetic analysis of bat-colonizing Bartonella spp. throughout the
      world demonstrates a distinct B. mayotimonensis cluster in the Northern
      Hemisphere. The findings of this field study highlight bats as potent reservoirs
      of human bacterial pathogens. 

PMID- 24856527
TI  - Antibiotic resistance in nosocomial respiratory infections.
AB  - Nosocomial respiratory infections are the most common acquired infections in
      patients with severe underlying conditions and are responsible for high morbidity
      and mortality in this patient population. Multidrug-resistant (MDR) pathogens are
      associated with hospital-acquired pneumonia (HAP) and ventilator-associated
      pneumonia (VAP). This article describes the etiology, epidemiology, pathogenesis,
      diagnosis, and treatment of HAP and VAP associated with antibiotic-resistant
      bacterial pathogens. 

PMID- 24856528
TI  - Nontuberculous mycobacteria in respiratory infections: advances in diagnosis and
      identification.
AB  - An urgent question that needs to be addressed rapidly by the mycobacteriology
      laboratory is whether Mycobacterium tuberculosis complex or NTM is involved. NAA
      assays are excellent tools for the purpose, and can be used directly on the
      clinical specimens of patients suspected of having mycobacterial disease,
      allowing same-day reporting of results. The CDC recommends using both liquid and
      solid media for growth detection of mycobacteria to decrease the time to
      detection and to increase the yield of growth detection. DNA sequencing of
      variable genomic regions offers a rapid, accurate, and relatively inexpensive
      method for the identification of mycobacteria. 

PMID- 24856529
TI  - Molecular diagnosis of tuberculosis and drug resistance.
AB  - Molecular drug susceptibility testing (MDST) provides rapid diagnosis of
      tuberculosis (TB) and detection of drug resistance with commendable sensitivity
      and specificity. MDST reduces unnecessary isolation or treatment, when a negative
      result for TB is obtained. Because of the possibility of false detection of
      rifampin resistance by probe-based MDST, confirmation by sequencing is
      recommended, especially in regions where the prevalence of resistance is low.
      Revealing mutation identity by sequencing offers opportunities to study drug
      minimum inhibitory concentrations for each mutation. Such information enables
      prediction of resistance levels, and may be helpful in formulating optimal
      regimens, when treatment options are limited. 

PMID- 24856530
TI  - Nonmolecular methods for the diagnosis of respiratory fungal infections.
AB  - Diagnosis of invasive fungal pneumonias by conventional culture methods is
      difficult to assess and often delayed. Nonmolecular fungal markers have emerged
      as an important adjunctive tool to support their diagnosis in combination with
      other clinical, radiologic, and microbiological criteria of invasive fungal
      diseases. Concerns about the sensitivity and specificity of some tests in
      different patient populations should lead to warnings about their widespread use.
      None can identify the emerging and particularly deadly fungal pathogens
      responsible for mucormycosis. The role of nonmolecular fungal markers should be
      better defined in combination with other microbiological and radiologic tools in
      preemptive antifungal strategies. 

PMID- 24856531
TI  - Interferon-gamma release assays.
AB  - Diagnosis of latent tuberculosis infection (LTBI) should be targeted toward
      individuals and groups with high risk of progression to active tuberculosis (TB).
      Low-risk populations should not be screened. Interferon-gamma release assays
      (IGRAs) perform as well or better than the tuberculin skin test in most targeted
      populations. IGRAs are preferred for bacille Calmette-Guerin (BCG)-vaccinated
      populations. A positive IGRA in a person at low risk for TB exposure should be
      confirmed with a repeat test or another method before recommending LTBI
      treatment. The choice of which IGRA to use is generally based on the costs and
      feasibility of performing the test. 

PMID- 24856532
TI  - Respiratory fungal infections: molecular diagnostic tests.
AB  - Fungal infection of the respiratory tract can take several forms, the most common
      of which is pneumonia. Fungal infection can occur in the immunocompetent
      typically as a result of inhalation of a large inoculum of fungal elements.
      However, the number of etiologic agents attacking immunocompetent individuals and
      causing significant infection is limited. Molecular assays are a potential
      additional and sensitive weapon that can be added to the diagnostic arsenal used
      by physicians to determine whether a fungus is definitively, probably, or
      possibly causing infection in a patient. 

PMID- 24856533
TI  - Rapid diagnosis of influenza: state of the art.
AB  - Much effort has been expended developing testing modalities for influenza viruses
      that are capable of providing rapid results to clinicians. Antigen-detection
      techniques, historically the only methods able to deliver results quickly, are
      still widely used despite concerns about sensitivity. Recently, nucleic acid
      amplification tests (NAATs), which can achieve rapid turnaround times and high
      sensitivity, have become available. In addition, NAATs can detect other
      respiratory pathogens. Although there are many theoretical advantages to rapid
      influenza testing, the clinical impact of testing in various patient populations
      must be considered against the cost and the analytical performance of the tests. 

PMID- 24856534
TI  - Antiviral resistance in influenza viruses: laboratory testing.
AB  - Influenza continues to be a significant health care issue. Although vaccination
      is the major line of defense, antiviral drugs play an important role in
      prophylaxis and disease management. Approved drugs for influenza are currently
      limited to those that target the viral matrix protein or neuraminidase enzyme.
      Resistance-associated sequence changes in the genes encoding these proteins have
      been extensively studied. Available methods for genotypic and phenotypic
      antiviral susceptibility testing have expanded and are being further developed
      and improved. The sporadic emergence of drug-resistant variants and the global
      spread of resistant strains have demonstrated the ongoing need for vigilant
      testing and surveillance. 

PMID- 24856536
TI  - Respiratory infections.

PMID- 24856535
TI  - Emerging respiratory viruses other than influenza.
AB  - Non-influenza respiratory virus infections are common worldwide and contribute to
      morbidity and mortality in all age groups. The recently identified Middle East
      respiratory syndrome coronavirus has been associated with rapidly progressive
      pneumonia and high mortality rate. Adenovirus 14 has been increasingly recognized
      in severe acute respiratory illness in both military and civilian individuals.
      Rhinovirus C and human bocavirus type 1 have been commonly detected in infants
      and young children with respiratory tract infection and studies have shown a
      positive correlation between respiratory illness and high viral loads, mono
      infection, viremia, and/or serologically-confirmed primary infection. 

PMID- 24856537
TI  - Delusions and underlying needs in older adults with Alzheimer's disease:
      influence of earlier life experiences and the current environment.
AB  - Delusions are one of the most severe psychiatric symptoms of individuals with
      Alzheimer's disease (AD), which often increase the stress experienced by
      caregivers. The purpose of this study was to understand the influences of earlier
      life experiences and the current environment on delusions, as well as the
      underlying needs of older adults with AD who experience delusions. Using an
      exploratory research design with a qualitative approach and purposive sampling,
      20 family caregivers were interviewed. Two psychosocial types of attributes of
      delusion were categorized: Type A, the influence of earlier life experiences; and
      Type B, current environmental influences. The underlying needs of those with
      delusions include physical comfort, a desire to be secure, and a sense of
      belonging. The contents of delusions are easily influenced by patients' earlier
      negative experiences and responsibilities, whereas the current environment exerts
      a crucial influence on the occurrence, frequency, and severity of specific
      delusions. These results can facilitate planning for patient-centered care by
      enhancing health care providers' understanding of the psychosocial and
      environmental attributes and needs behind delusions.

PMID- 24856538
TI  - Photoelectron interference in metallocenes: a probe of geometrical and electronic
      structure.
AB  - The present work concerns the study of high-energy structures in the
      photoionization of Mg and Be metallocenes due to photoelectron diffraction. The
      influence of geometrical structure is studied by varying the metal-ring distance
      in MgCp2, as well as that in the permethylated compounds MgCp2* and BeCp2*. The
      cross section ratios relative to the two outermost valence ionizations have been
      studied and found to be very sensitive to the value of the metal-ring distance
      and to be able to resolve ambiguities in present experimental values. Further
      differences are attributed to minor changes in the electronic structure. The
      results confirm that long-range oscillations in molecular photoemission cross
      sections constitute a general phenomenon and are an easily measurable observable
      that can be used to obtain important information on the geometric and electronic
      structure of the target.

PMID- 24856539
TI  - Fabrication of cobalt porphyrin. Electrochemically reduced graphene oxide hybrid
      films for electrocatalytic hydrogen evolution in aqueous solution.
AB  - Here we report on an experimental study of an electrocatalyst for the hydrogen
      evolution reaction (HER) based on cobalt porphyrin and electrochemically reduced
      graphene oxide (ERGO) functional multilayer films, which are prepared by the
      alternating layer-by-layer (LBL) assembly of negatively charged graphene oxide
      (GO) and positively charged [tetrakis (N-methylpyridyl) porphyrinato] cobalt
      (CoTMPyP) in combination with an electrochemical reduction procedure. The
      resulting [ERGO@CoTMPyP]n multilayer films display relatively high
      electrocatalytic activity and superior stability toward HER in alkaline media.
      Electrochemical studies indicate that CoTMPyP in the multilayer films is the
      active catalyst for the reduction of protons to dihydrogen. 

PMID- 24856542
TI  - [Subcutaneous tumour in the finger of an 11 year-old girl].

PMID- 24856540
TI  - Development of a new photochromic ion channel blocker via azologization of
      fomocaine.
AB  - Photochromic blockers of voltage gated ion channels are powerful tools for the
      control of neuronal systems with high spatial and temporal precision. We now
      introduce fotocaine, a new type of photochromic channel blocker based on the long
      lasting anesthetic fomocaine. Fotocaine is readily taken up by neurons in brain
      slices and enables the optical control of action potential firing by switching
      between 350 and 450 nm light. It also provides an instructive example for
      "azologization", that is, the systematic conversion of an established drug into a
      photoswitchable one. 

PMID- 24856543
TI  - [Aorto-cavitary fistulae in infective native valve endocarditis].

PMID- 24856544
TI  - [Impact of introducing an enterovirus polymerase chain reaction in the management
      of aseptic meningitis].
AB  - INTRODUCTION: The diagnosis of aseptic meningitis, based on an enterovirus PCR
      (EV-PCR) in cerebrospinal fluid, is a rapid and sensitive test. OBJECTIVE: To
      assess the impact of introducing EV-PCR on the use of antibiotics and hospital
      length of stay in aseptic meningitis. MATERIAL AND METHODS: A prospective study
      that included children with aseptic meningitis during one year. The patients
      prior to the introduction of the test formed the control group. RESULTS: The
      performance of the PCR test was associated with less use of antibiotics compared
      to the control group (16.2% vs 41.4%, P=.029) and with fewer days of
      administration (.54 vs. 2 days, P=.014). A non-significant decrease in length of
      stay (3.57 vs. 4.21 days, P=.376) was also observed in the study group.
      CONCLUSION: The introduction of the EV-PCR test decreases the use of antibiotics
      and hospital length of stay.

PMID- 24856545
TI  - Affective temperament profiles and clinical correlates in patients with epilepsy:
      a link from mood disorders.
AB  - BACKGROUND: The current study sought to investigate the affective temperaments of
      patients with epilepsy and possible relationships between disease characteristics
      and temperament profiles. METHODS: A total of 70 adults with epilepsy and 70
      healthy volunteers completed the Beck Depression Inventory (BDI), the Beck
      Anxiety Inventory and the Temperament Evaluation of Memphis, Pisa, Paris and San
      Diego (TEMPS-A). RESULTS: Patients with epilepsy had higher scores on these three
      scales than healthy controls. With respect to temperaments, irritable temperament
      alone was significantly higher in patients than controls. Irritable temperament
      also had a significant positive correlation with psychiatric history, whereas
      depressive temperament had a significant positive correlation with illness and
      treatment duration. Patients who had suffered simple partial and complex partial
      seizures had higher anxious temperament scores than patients with generalized
      epilepsy. LIMITATIONS: Because the study group was recruited through consecutive
      patients seen in a single neurology clinic, our findings may not be
      representative of PWE in general. CONCLUSIONS: Because irritability is one of the
      key symptoms of interictal dysphoric disorder and because TEMPS-A irritable
      temperament and BDI scores were found to be significantly related, the high rate
      of irritable temperament in our patient sample may be associated with depressive
      mood. We may suggest that at least some of the affective symptoms in patients
      with epilepsy and the historical concept of "epileptic personality" may be
      explained by affective temperaments.

PMID- 24856547
TI  - Koukopoulos' diagnostic criteria for mixed depression: a validation study.
AB  - BACKGROUND: Mixed depression (MxD) is one subtype of depressive experiences
      within the depressive spectrum. MxD definition is debated among experts.
      Koukopoulos' proposed diagnostic criteria focused primarily on psychic agitation,
      marked irritability, and intense mood lability as markers of a mixed depressive
      episode. The present study validates Koukopoulos' criteria as diagnostic for MxD.
      METHODS: A sample of 435 patients from the International Mood Network (IMN),
      multi-center, international network of sites, and the Centro LucioBini of Rome
      was analyzed. Koukopoulos' criteria were assessed in all patients. RESULTS: The
      most prevalent MxD criteria were "absence of psychomotor retardation" (84%),
      "mood lability or marked reactivity" (78%), and "psychic agitation or inner
      tension" (75%). Multivariable predictors of a MxD (+) diagnosis were: higher
      current CGI (OR=1.23, 95% CI 1.23, 2.84), lower rates of previous bipolar type I
      diagnosis (OR=0.54, 95% CI -3.28, -0.13), mixed symptoms on the index episode
      (OR=10.02, 95% CI 2.32, 24.12), rapid cycling course (OR=2.6 95% CI 1.45, 3.56),
      past substance abuse (OR=3.02, 95% CI 2.01, 5.67) and lower education status
      (OR=0.44, 95% CI -3.23, -0.98). This model showed a sensitivity of 76.4%,
      specificity of 86.3%, negative predictive value of 75%, and positive predictive
      value of 86%. LIMITATIONS: An external validation of these criteria in an
      independent sample is warranted. CONCLUSION: A broad definition of mixed
      depression was internally validated with multiple diagnostic validators and was
      sensitively and specifically predicted. Contrary to DSM-5, Koukopoulos' broad
      criteria include agitation, irritability and mood lability as core features.

PMID- 24856548
TI  - Obsessive-compulsive symptoms in a normative Chinese sample of youth: prevalence,
      symptom dimensions, and factor structure of the Leyton Obsessional Inventory-
      Child Version.
AB  - BACKGROUND: Chinese adolescents face life stresses from multiple sources, with
      higher levels of stress predictive of adolescent mental health outcomes,
      including in the area of obsessive-compulsive disorders (OCD). Valid assessment
      of OCD among this age group is therefore a critical need in China. This study
      aims to standardise the Chinese version of the Leyton short version scale for
      adolescents of secondary schools in order to assess this condition. METHODS:
      Stratified randomly selected adolescents were selected from four high schools
      located in Beijing, China. The Chinese version of the Leyton scale was
      administered to 3221 secondary school students aged between 12 and 18 years. A
      high response rate was achieved, with 3185 adolescents responding to the survey
      (98.5 percent). Exploratory factor analysis (EFA) extracted four factors from the
      scale: compulsive thoughts, concerns of cleanliness, lucky number, repetitiveness
      and repeated checking. The four-factor structures were confirmed using
      Confirmatory Factor Analysis (CFA). RESULTS: Overall the four-factor structure
      had a good model fit and high levels of reliability for each individual dimension
      and reasonable content validity. Invariance analyses in unconstrained, factor
      loading, and error variance models demonstrated that the Leyton scale is
      invariant in relation to the presence or absence OCD, age and gender.
      Discriminant validity analysis demonstrated that the four-factor structure scale
      also had excellent ability to differentiate between OCD and non-OCD students,
      male and female students, and age groups. LIMITATIONS: The dataset was a non
      clinical sample of high school students, rather than a sample of individuals with
      OCD. Future research may examine symptom structure in clinical populations to
      assess whether this structure fits into both clinical and community population.
      CONCLUSIONS: The structure derived from the Leyton short version scale in a non
      clinical secondary school sample of adolescents, suggests that a four-factor
      solution can be utilised as a screening tool to assess adolescents'
      psychopathological symptoms in the area of OCD in mainland Chinese non-clinical
      secondary school students.

PMID- 24856546
TI  - Imbalanced hippocampal functional networks associated with remitted geriatric
      depression and apolipoprotein E epsilon4 allele in nondemented elderly: a
      preliminary study.
AB  - BACKGROUND: Apolipoprotein E (APOE) epsilon4 allele and a history of geriatric
      depression are confirmed risk factors of Alzheimer's disease (AD). Coexistence of
      both factors could notably enhance the risk of cognitive impairment in
      nondemented elderly. However, neural basis of the association remains unclear.
      METHODS: Thirty-one remitted geriatric depression (RGD) patients and 29
      cognitively normal subjects were recruited and underwent resting-state functional
      MRI scans. They were further divided into four groups according to their APOE
      genotypes. Hippocampal seed-based network analysis and two-way factorial analysis
      of covariance were employed to detect the main effects and interactive effects of
      RGD and APOE epsilon4 allele on the hippocampal functional connectivity (HFC)
      networks. Partial correlation analysis was applied to examine the cognitive
      significance of these altered HFC networks. RESULTS: The HFC networks of RGD
      patients were decreased in the dorsal frontal and increased in the right temporal
      occipital regions. For APOE epsilon4 carriers, the HFC networks were reduced
      primarily in medial prefrontal regions and enhanced in the bilateral insula.
      Additionally, when both factors coexisted, the left HFC network was significantly
      disrupted in the dorsal anterior cingulate cortex and increased in somatomotor
      and occipital regions. Importantly, the extent of network alterations was linked
      to inferior cognitive performances in RGD patients and APOE epsilon4 carriers.
      LIMITATIONS: The small sample size may limit the generalizability of our
      findings. CONCLUSIONS: RGD and APOE epsilon4 allele, and their interaction, are
      associated with the imbalanced HFC network, which may contribute to cognitive
      deterioration for subjects with a high risk of AD.

PMID- 24856549
TI  - Beliefs about depression--do affliction and treatment experience matter? Results
      of a population survey from Germany.
AB  - BACKGROUND: There is not much known about the associations of beliefs about
      depression (depression literacy) with a history of depression and treatment
      experience. METHODS: Analyses were based on a telephone survey in two large
      German cities (Hamburg and Munich). Written vignettes with typical signs and
      symptoms suggestive of a depression were presented to 1293 respondents.
      Respondents were then asked about beliefs about causes, symptoms, prevalence, and
      treatment using a standardized questionnaire. For the analysis respondents were
      divided into three groups: (1) people who never had a depression, (2) people who
      had a depression but were not treated and (3) people with treatment experience.
      RESULTS: Respondents with experience in treatment for depression were more likely
      to correctly recognize the disorder, to positively evaluate treatability and to
      favor external factors (adverse conditions in childhood and psychosocial stress)
      as potential causes of depression compared to those who never were afflicted.
      There were no significant differences between these two groups regarding beliefs
      about the effectiveness of treatment options. There were only few significant
      differences in depression literacy between respondents who have a history of
      depression but have not sought help and those who never were afflicted.
      LIMITATIONS: The three groups were constituted on the basis of respondents' self
      reports, not medical diagnoses. CONCLUSIONS: Our findings only partly support the
      general assumption that being afflicted and having sought help is associated with
      beliefs closer to those of professionals.

PMID- 24856550
TI  - FKBP5 polymorphism is associated with major depression but not with bipolar
      disorder.
AB  - BACKGROUND: Altered activity of hypothalamus-pituitary-adrenal glands (HPA) axis
      in response to stress underlies the pathogenesis of mood disorders such as
      depression and bipolar disorder. Chaperone proteins regulate sensitivity of
      glucocorticoid receptor (GR) to steroids. We hypothesized that genetic variants
      within the FKBP5 - gene encoding co-chaperone protein essential in GR signaling -
      may influence the susceptibility to major depressive disorder and bipolar
      disorder. METHODS: In the study participated 528 bipolar patients, 218 patients
      with major depressive disorder and 742 subjects from control group. Genotypes for
      eight FKBP5 polymorphisms (rs1360780, rs755658, rs9470080, rs4713916, rs7748266,
      rs9296158, rs9394309, rs3800373) were established by TagMan SNP Genotyping Assays
      (Applied Biosystems). Linkage disequilibrium analysis for FKBP5 gene was done in
      Haploview. Gene-gene interactions between FKBP5 and NR3C1 polymorphisms (reported
      previously) were analyzed using the multidimensionality-reduction method (MDR).
      RESULTS: We have observed an association between five FKBP5 polymorphisms
      (rs1360780, rs9470080, rs4713916, rs9296158 and rs9394309) and major depressive
      disorder (p=0.011; p=0.007, p=0.038; p=0.030; p=0.018, respectively), but not
      bipolar disorder. In linkage disequilibrium analysis we found that seven FKBP5
      polymorphisms build haplotype block (rs3800373, rs755658, rs9296158, rs7748266,
      rs1360780, rs9394309, rs9470080, respectively). We observed that two haplotype
      combinations (ACATTGT and CCACTAT) were significantly more frequent in the MDD
      patients than in controls (p=0.014 and p=0.043). We have not observed such an
      association for BD patients. We have found that interaction between rs9470080 of
      FKBP5 and rs6198 of NR3C1 influences MDD risk. LIMITATIONS: The main limitations
      of this study include low power and limited sample size of MDD patients.
      CONCLUSIONS: Single markers and haplotypes of FKBP5 gene and the interaction with
      glucocorticoid receptor gene (NR3C1) may influence MDD predisposition.

PMID- 24856551
TI  - Increased platelet intracellular calcium ion concentration is specific to bipolar
      disorder.
AB  - BACKGROUND: Increased baseline ([Ca(2+)]B) and agonist-stimulated ([Ca(2+)]s)
      free intracellular calcium ion concentrations ([Ca(2+)]i) are well-replicated
      findings in bipolar disorder, but whether this finding is specific to that
      condition and if so, whether it is a marker of the mood disorder or a feature
      seen in other disorders such as psychosis has remained unclear. METHODS: Platelet
      [Ca(2+)]i was assessed in 15 inpatients with psychotic and nonpsychotic mania, 17
      schizophrenia inpatients, and 17 matched controls. RESULTS: Platelet [Ca(2+)]B
      and [Ca(2+)]s were significantly higher than controls in bipolar disorder but not
      schizophrenia. Variability of [Ca(2+)]B was significantly increased in bipolar
      disorder regardless of the presence of psychosis, but not in schizophrenia.
      LIMITATIONS: Use of antipsychotic drugs by the majority of both patient groups
      may have obscured elevated [Ca(2+)]i in schizophrenia, or may have masked a
      difference between psychotic and nonpsychotic bipolar disorder. Measurement of
      [Ca(2+)]i is too labor intensive to become a routine test for diagnosis or
      prediction of treatment response. CONCLUSIONS: Elevated intracellular Ca(2+)
      signaling may be a marker of primary cellular hyperactivity that could contribute
      to comorbid conditions such as hypertension and neuronal apoptosis. Since lithium
      and carbamazepine attenuate increased [Ca(2+)]i, further research may demonstrate
      a correlation between normalization of [Ca(2+)]i and response to one of these
      medications, and further research may clarify whether a subgroup of patients may
      respond well to calcium channel antagonists.

PMID- 24856552
TI  - Towards validation of the short TEMPS-A in non-clinical adult population in
      Serbia.
AB  - BACKGROUND AND AIMS: This study represents the standardisation of the Serbian
      version of the TEMPS-A scale on non-clinical adult population, as well as
      external validation with TCI-R scale of temperaments which has already been
      evaluated on Serbian population. METHODS: The TEMPS-A has been administered to
      570 healthy adults without histories of mental disorders, 47% male, 53% female,
      aged between 20 and 76 (M=35.55; SD=14.14). In line with the state census data,
      the sampling was partially stratified according to gender, age categories,
      education and regional area of the participants. RESULTS: In contrast to many
      other studies, six factors were extracted herein, including 41 items with
      loadings above .50, explaining 44.40% of the total variance. The internal
      consistency of the scale was alpha=.83, and the average test-retest coefficient
      (rho=.82) indicates a stable reliability. The highest positive correlations were
      obtained between the depressive and cyclothymic scales, depressive and anxious
      scales, and cyclothymic with anxious scales. The highest values were detected on
      hyperthymic and the lowest on depressive temperament. The highest positive
      correlations were reported between harm avoidance (measured by the TCI-R) and
      depressive, anxious, cyclothymic temperament, and between novelty seeking and
      hyperthymic temperament. The highest negative correlation was detected between
      harm avoidance and hyperthymic. Finally, females scored higher on depressive,
      cyclothymic and anxious, while males scored higher on hyperthymic temperament.
      LIMITATIONS: The participants' educational background was slightly higher than
      that of the general population of Serbia. Since the scale is aimed at its
      administration in clinical population as well, it is necessary that its structure
      and validity be also tested on specific clinical subpopulations in the future.
      CONCLUSIONS: The current study is significant in having confirmed that the TEMPS
      A can be reliably and validly used in identifying affective temperaments in the
      adult nonclinical population in Serbia, which provides the basis and norms for
      future comparisons with clinical subpopulations.

PMID- 24856554
TI  - Efficacy of olanzapine monotherapy in the treatment of bipolar depression with
      mixed features.
AB  - BACKGROUND: This analysis investigated the correlations between the efficacy of
      olanzapine monotherapy and the number of concurrent manic symptoms in patients
      treated for bipolar depression. METHODS: Pooled data from 2 placebo-controlled
      olanzapine studies in patients with bipolar I depression were analyzed (total
      1214 patients; 690 olanzapine monotherapy patients and 524 placebo patients).
      Patients were categorized for mixed features by the number of concurrent manic
      symptoms at baseline (0, 1 or 2, and >=3, respectively, as measured by a Young
      Mania Rating Scale item score >=1). Efficacy was evaluated by change in
      Montgomery-Asberg Depression Rating Scale (MADRS) total score from baseline to 6
      weeks. RESULTS: Least-squares mean differences between olanzapine and placebo in
      the change of MADRS total scores were -3.76 (p=0.002), -3.20 (p<0.001), and -3.44
      (p=0.002) for mixed features 0, 1 or 2, and >=3, respectively. The response rates
      for olanzapine versus (vs.) placebo were 52.6% vs. 39.8%, 50.3% vs. 40.0%, and
      42.2% vs. 33.7% for mixed features 0, 1 or 2, and >=3, respectively. The
      remission rates for olanzapine vs. placebo group were 46.1% vs. 34.3%, 39.5% vs.
      32.0%, and 34.8% vs. 24.1% for mixed features 0, 1 or 2, and >=3, respectively.
      No significant interaction between mixed features and treatment was seen in the
      MADRS changes or response and remission rates. LIMITATIONS: Post hoc analyses of
      the data from 2 previous randomized clinical studies. CONCLUSIONS: Olanzapine
      monotherapy was shown to be effective in the treatment of bipolar depression
      irrespective of the presence of concurrent manic symptoms.

PMID- 24856553
TI  - Neural response to reward anticipation in those with depression with and without
      panic disorder.
AB  - BACKGROUND: One of the hallmark features of major depressive disorder (MDD) is
      reduced reward anticipation. There have been mixed findings in the literature as
      to whether reward anticipation deficits in MDD are related to diminished
      mesolimbic activation and/or enhanced dorsal anterior cingulate activation
      (dACC). One of the reasons for these mixed findings is that these studies have
      typically not addressed the role of comorbid anxiety, a class of disorders which
      frequently co-occur with depression and have a common neurobiology. METHODS: The
      aim of the current study was to examine group differences in neural responses to
      reward anticipation in 40 adults with either: (1) current MDD with no lifetime
      diagnosis of an anxiety disorder (MDD-only), (2) current MDD with comorbid panic
      disorder (MDD-PD), or (3) no lifetime diagnosis of psychopathology. All
      participants completed a passive slot machine task during a functional magnetic
      resonance imaging (fMRI) scan. RESULTS: Analyses indicated that there were no
      group differences in activation of mesolimbic reward regions; however, the MDD
      only group exhibited greater dACC activation during the anticipation of rewards
      compared with the healthy controls and the comorbid MDD-PD group (who did not
      differ from each other). LIMITATIONS: The sample size was small which limits
      generalizability. CONCLUSIONS: These findings provide preliminary support for the
      role of hyperactive dACC functioning in reduced reward anticipation in MDD. They
      also indicate that comorbid anxiety may alter the association between MDD and
      neural responding to reward anticipation.

PMID- 24856555
TI  - Somatic, but not cognitive, symptoms of anxiety predict lower levels of physical
      activity in panic disorder patients.
AB  - BACKGROUND: Anxiety disorders have gathered much attention as possible risk
      factors for the development of cardiovascular disease (CVD), possibly mediated by
      an unhealthy lifestyle (e.g. low physical activity). However, prospective studies
      on anxiety disorders and CVD show conflicting results. A possible explanation is
      that somatic symptoms of anxiety may have a more specific cardiovascular effect
      than cognitive symptoms across different anxiety disorders. The present study
      investigated the association between cognitive and somatic symptoms of anxiety
      and physical activity (PA) in a sample of panic disorder (PD) outpatients.
      METHODS: One-hundred and two outpatients with a lifetime diagnosis of PD from a
      previously studied cohort were contacted. Patients were evaluated throughout the
      MINI, the Beck Anxiety Inventory (BAI) and the International Physical Activity
      Questionnaire (IPAQ). After performing a multivariate regression analysis, groups
      were divided into high and low somatic anxiety. RESULTS: Patients with high
      somatic anxiety showed a significantly higher prevalence of low level of PA as
      compared to those with low somatic anxiety (62.5 versus 34.3%; chi2= 5.33; df=1;
      P=.021). Somatic symptoms of anxiety remained the only important predictors of
      low level of PA (odds ratio [OR] 2.81; 95% CI 1.00-7.90; p=.050) in the
      multivariate model. LIMITATIONS: The main limitations of the present study are
      the cross-sectional design and the small sample size. CONCLUSIONS: Results
      support specific effects of somatic symptoms of anxiety on risk for low level of
      PA, which might explain inconsistent results regarding CVD risk in the
      literature.

PMID- 24856556
TI  - Reliability, validity and preliminary hypothesis tests for the English version of
      the Psychological Strain Scales (PSS).
AB  - BACKGROUND: The original Psychological Strain Scales (PSS) was published with
      data from a sample of Chinese population, which consisted of four strain scales:
      value strain, aspiration strain, deprivation strain, and coping strain. This
      study aims to validate and develop the English version of the PSS instrument.
      METHOD: Together with the PSS, Moos's Coping Response Inventory (CRI),
      Spielberger Trait-Anxiety scale, CES-D depression scale, and the NCS suicidal
      behavior scales were administered in a survey to a sample (N=280) of American
      college students. Item-total statistics, Cronbach's Alpha, Guttman Split-Half
      coefficient, factor analyses, correlation analysis and t tests were applied to
      test the reliability and validity of the English version of the PSS. Univariate
      and multivariable regression analyses were operated to know how extent the PSS
      predicts psychopathology such as anxiety, depression and suicidal behaviors.
      RESULTS: Cronbach's Alpha coefficient of PSS was 0.936. The Split-Half
      coefficient of PSS was 0.839. The reliability of the PSS was excellent. The
      factor analysis results demonstrated strong construct validity of each scale. The
      criterion validity and the discriminant validity were both excellent for the
      English version of PSS instrument. CONCLUSIONS: With the excellent scores on both
      reliability and validity, the English version of the PSS scales can be an
      excellent measurement for estimating the psychological strain levels of American
      college students as well as predicting their psychopathology. The PSS can be
      applicable for research to evaluate and predict suicidal behaviors and mental
      disorders.

PMID- 24856557
TI  - S-adenosyl methionine (SAMe) versus escitalopram and placebo in major depression
      RCT: efficacy and effects of histamine and carnitine as moderators of response.
AB  - OBJECTIVE: To assess the antidepressant efficacy of S-adenosyl methionine (SAMe),
      a naturally occurring methyl donor, versus the selective serotonin reuptake
      inhibitor (SSRI) escitalopram and a placebo control; and to determine whether
      serum histamine or carnitine levels modified treatment response. METHODS: We
      examined a subsample (n=144) from one site of a two-site study of adults with
      diagnosed Major Depressive Disorder (MDD), recruited from 4/13/05 to 12/22/09,
      who consented to the additional blood draw for serum histamine and carnitine
      levels. After washout, eligible subjects were randomized to SAMe (1600
      3200mg/daily), escitalopram (10-20mg/daily), or matching placebo for 12 weeks of
      double-blind treatment (titration at week 6 in non-response). RESULTS: On the
      primary outcome of the Hamilton Depression Rating Scale (HAMD-17), a significant
      difference in improvement was observed between groups from baseline to week 12
      (p=0.039). The effect size from baseline to endpoint was moderate to large for
      SAMe versus placebo (d=0.74). SAMe was superior to placebo from week 1, and to
      escitalopram during weeks 2, 4, and 6. No significant effect was found between
      escitalopram and placebo or SAMe. Response rates (HAMD-17>=50% reduction) at
      endpoint were 45%, 31%, and 26% for SAMe, escitalopram, and placebo,
      respectively; while remission rates (HAM-D<=7) were 34% for SAMe (p=0.003), 23%
      for escitalopram (p=0.023), and 6% for placebo. No correlation between baseline
      histamine level and reduction of HAMD-17 score was found for either the SAMe or
      escitalopram groups. Baseline carnitine levels were also not found to moderate
      response to either treatment. LIMITATIONS: While SAMe appears to be an effective
      antidepressant agent, the overall findings from the parent study (which showed no
      significant difference between groups due to site differences) must be taken into
      consideration. CONCLUSIONS: These preliminary results provide encouraging
      evidence for the use of SAMe in the treatment of MDD. Histamine and carnitine
      serum level may not necessarily moderate response to SAMe.

PMID- 24856558
TI  - Reference values for the Body Image Concern Inventory (BICI), the Whitely Index
      (WI), and the Checklist Individual Strength (CIS-20R): The Leiden Routine Outcome
      Monitoring Study.
AB  - BACKGROUND: The Body Image Concern Inventory (BICI), the Whitely Index (WI), and
      the Checklist Individual Strength (CIS-20R) are three questionnaires often
      incorporated in routine outcome monitoring (ROM). Respectively, they assess
      symptom severity in patients with body dysmorphic disorder, hypochondriasis, and
      chronic fatigue syndrome. We aimed to generate reference values for a healthy
      population and for a population of patients fulfilling diagnostic criteria for at
      least one of BDD, hypochondriasis, and CFS, treated in specialized mental health
      care. METHODS: The healthy ROM reference-group (n=648) was recruited through
      general practitioners. These subjects were matched for age and sex with the ROM
      patient-group (n=823). To define limits (i.e., cut-off-values) for one-sided
      reference intervals (5th percentile [P5] for ROM patient-group and 95th
      percentile [P95] for ROM reference-group) the outermost 5% of observations were
      used. Discriminative powers were evaluated by receiver operating characteristics
      (ROC) analyses RESULTS: Cut-off-values (P95 ROM reference-group) were 55 for the
      BICI, 6 for the WI, and 92 for the CIS-20R. These values differed for men and
      women, being mostly higher for women. The discriminative power of all three
      somatoform questionnaires was very high. LIMITATIONS: Substantial non-response
      and limited generalizability. CONCLUSIONS: For the BICI, WI, and CIS-20R a
      comprehensive set of reference values was obtained. The reference values may
      support clinical decisions regarding adjusting or terminating therapy, and
      possible referral.

PMID- 24856560
TI  - A three-year longitudinal study of affective temperaments and risk for
      psychopathology.
AB  - BACKGROUND: Affective temperaments are presumed to underlie bipolar
      psychopathology. The TEMPS-A has been widely used to assess affective
      temperaments in clinical and non-clinical samples. Cross-sectional research
      supports the association of affective temperaments and mood psychopathology;
      however, longitudinal research examining risk for the development of bipolar
      disorders is lacking. The present study examined the predictive validity of
      affective temperaments, using the TEMPS-A, at a three-year follow-up assessment.
      METHODS: The study interviewed 112 participants (77% of the original sample) at a
      three-year follow-up of 145 non-clinically ascertained young adults
      psychometrically at-risk for bipolar disorders, who previously took part in a
      cross-sectional examination of affective temperaments and mood psychopathology.
      RESULTS: At the reassessment, 29 participants (26%) met criteria for bipolar
      spectrum disorders, including 13 participants who transitioned into disorders
      during the follow-up period (14% of the originally undiagnosed sample).
      Cyclothymic/irritable and hyperthymic temperaments predicted both total cases and
      new cases of bipolar spectrum disorders at the follow-up. Cyclothymic/irritable
      temperament was associated with more severe outcomes, including DSM-IV-TR bipolar
      disorders, bipolar spectrum psychopathology, major depressive episodes, and
      substance use disorders. Hyperthymic temperament was associated with bipolar
      spectrum psychopathology and hypomania, whereas dysthymic temperament was
      generally unassociated with psychopathology and impairment. LIMITATIONS: The
      present sample of young adults is still young relative to the age of onset of
      mood psychopathology. CONCLUSIONS: These results provide the first evidence of
      the predictive validity of affective temperaments regarding risk for the
      development of bipolar psychopathology. Affective temperaments provide a useful
      construct for understanding bipolar psychopathology.

PMID- 24856559
TI  - Temperamental dimensions of the TEMPS-A in females with co-morbid bipolar
      disorder and bulimia.
AB  - OBJECTIVES: We investigated the effect of co-morbid bipolar disorder and bulimia
      on temperamental dimensions measured by TEMPS-A, relative to "pure" bulimia and
      "pure" bipolar disorder, in female patients. METHODS: The study was performed on
      47 patients with bipolar disorder (BD) with a mean age of 36+/-10 years, 96
      patients with bulimia or bulimic type of anorexia, mean age 26+/-9 years and 50
      control healthy females (HC), mean age 29+/-6 years. Among bulimic patients, a
      group of 68 subjects with co-morbid bulimia with bipolarity (BD+B) was
      identified, based on positive score of the Mood Disorder Questionnaire (MDQ). The
      TEMPS-A questionnaire, 110 questions version, has been used, evaluating five
      temperament domains: depressive, cyclothymic, hyperthymic, irritable and anxious.
      Parametric analysis was performed for 4 groups (BD, "pure" bulimia (PB), BD+B and
      HC), with 28 subjects randomly chosen from each group, using analysis of variance
      and cluster analysis. RESULTS: All clinical groups significantly differed from
      control group by having higher scores of depressive, cyclothymic, irritable and
      anxious temperaments and lower of hyperthymic one. Among patients, significantly
      higher scores of cyclothymic and irritable temperaments were found in BD+B
      compared to both PB and BD. These differences were also reflected in cluster
      analysis, where two clusters were identified. LIMITATIONS: Bipolarity in bulimic
      patients assessed only by the MDQ. CONCLUSIONS: These results show that co-morbid
      bulimia and bipolar disorder is characterized by extreme dimensions of both
      cyclothymic and irritable temperaments, significantly higher than each single
      diagnosis. Possible clinical implications of such fact are discussed.

PMID- 24856561
TI  - Associations between circadian activity rhythms and functional brain
      abnormalities among euthymic bipolar patients: a preliminary study.
AB  - BACKGROUND: Working memory and underlying functional brain deficits have been
      observed in euthymic bipolar disorder (BD) patients, though there is
      heterogeneity in the degree of deficits. Sleep/circadian rhythm abnormalities are
      thought to be a core component of BD and may explain some of the heterogeneity in
      functional abnormalities. This preliminary study examined associations between
      sleep/circadian rhythm abnormalities and functional magnetic resonance imaging
      (fMRI) brain response on a working memory task among BD patients. METHODS:
      Fourteen euthymic medicated BD patients wore an actigraph for 7 days before
      undergoing fMRI with a working memory task. Two matched healthy comparison (HC)
      groups were used (14 in each sample). One group completed the actigraphy portion
      and the other completed the fMRI portion of the study. Circadian activity rhythm
      and sleep variables were calculated and compared between BD and HC participants.
      Variables that significantly differed were used to examine the association
      between activity rhythms/sleep abnormalities and fMRI working memory brain
      response in anatomically defined regions. RESULTS: Sleep efficiency and the
      rhythm robustness, mesor, and amplitude-to-width ratio were significantly
      abnormal in BD patients. Individual variability in all the sleep/circadian
      variables was significantly associated with the degree of abnormality of brain
      response in the dorsolateral prefrontal cortex and supramarginal gyri.
      LIMITATIONS: Small sample size and multiple comparison groups limit the
      interpretability of these findings. CONCLUSIONS: BD patients have abnormal
      activity rhythms and sleep efficiency, which are associated with abnormal working
      memory brain response. These preliminary findings support the notion that the
      sleep/circadian system is important in the functional brain deficits among BD
      patients.

PMID- 24856562
TI  - Psychopathology and functioning among children of treated depressed fathers and
      mothers.
AB  - OBJECTIVE: Recent findings suggest that remissions of maternal depression are
      associated with decrease in offspring psychopathology. Little is known about the
      offspring effects of decrease in paternal depression. METHOD: The offspring of
      married fathers and married mothers were compared. The analysis was restricted to
      married parents to control for the confounding effect of single parenthood which
      was more prevalent among depressed mothers. At baseline all parents met criteria
      for major depressive disorder (MDD), and participated in a 3 month randomized
      controlled trial to treat depression with a 6 month follow-up. Married parents
      (N=43) and their children aged 7-17 years (N=78) were assessed independently
      through direct interviews of children and parents at baseline and followed for 9
      months. Child assessors were blind to the clinical status of parents and
      uninvolved in their treatment. RESULTS: At baseline, children of depressed
      fathers, compared to children of depressed mothers, had significantly fewer
      psychiatric disorders (11% vs. 37%; p=0.012) and less impairment as measured by
      the Columbia Impairment Scale (6.5 vs. 11.6; p=0.009). Over time, with treatment
      of parental depression, the prevalence of most child symptoms decreased among
      children of depressed mothers, but changed little among children of depressed
      fathers. LIMITATIONS: The main limitation of the study is the small number of
      fathers and their offspring included in the study. CONCLUSION: Maternal as
      compared to paternal depression had a greater impact on children. With treatment
      of parental depression the differential prevalence of child symptoms by parental
      gender narrowed over time. The clinical implication is that children may benefit
      from treatment of their depressed parents.

PMID- 24856564
TI  - Blood biomarkers of depression track clinical changes during cognitive-behavioral
      therapy.
AB  - BACKGROUND: Results from convergent genomics indicated new peripheral biomarkers
      for mood states. We sought to investigate the clinical utility of the BioM-10
      Mood Panel, a peripheral biomarker set of low vs. high mood states, in the
      diagnosis of major depressive episode and to monitor the effectiveness of
      cognitive-behavioral therapy (CBT). METHOD: 44 patients with a first episode of
      major depression and 30 healthy control subjects participated in the study. The
      BioM-10 panel's gene expression profile was measured from whole peripheral blood
      with the Affymetrix Human Genome U133 Plus 2.0 Gene Chips, focusing on 10 top
      genes related to high mood states (MBP, EDG2, FZD3, ATXN1, and EDNRB) and low
      mood states (FGFR1, MAG, PMP22, UGT8, and ERBB3). We studied gene expression
      before and after CBT. RESULTS: The BioM-10 prediction score discriminated
      patients and controls with high sensitivity (84%) and specificity (90%). There
      was an increase in the BioM-10 prediction score after CBT relative to the
      pretreatment value. Clinical improvement was associated with higher prediction
      scores reflecting a greater ratio of high mood markers relative to low mood
      markers. LIMITATIONS: Sample size was small for a genome-wide microarray study.
      Convergent genomic studies have not been conducted in major depressive disorder.
      More evidence is needed from patients with severe, recurrent, and chronic forms
      of depression. CONCLUSIONS: The BioM-10 panel is a promising tool as a biomarker
      setup for the evaluation of low and high mood states across diagnostic
      categories. The panel includes genes related to growth factor pathways and
      myelination, which may provide new insights into the pathophysiology of mood
      dysregulation.

PMID- 24856563
TI  - Antenatal and postnatal maternal mood symptoms and psychiatric disorders in pre
      school children from the 2004 Pelotas Birth Cohort.
AB  - BACKGROUND: Maternal mood symptoms have been associated with psychiatric
      disorders in children. This study aimed to assess critical periods when maternal
      symptoms would be more deleterious. METHODS: Cohort of 4231 births followed-up in
      the city of Pelotas, Brazil. Mood symptoms during pregnancy were self-reported by
      mothers at perinatal interview; and at 3-months postpartum, mothers answered the
      Self-Reporting Questionnaire. Psychiatric disorders in 6-year-old children were
      evaluated through the Development and Well-Being Assessment instrument. Odds
      ratios with 95% confidence intervals (95% CI) were calculated by logistic
      regression. RESULTS: Prevalence of mood symptoms in pregnancy was 24.6% (23.2
      26.0%) and at three months postpartum 22.5% (21.1-23.9%). Prevalence of mental
      disorders in children was 13.3% (12.2-14.4%). After adjustment for confounders
      children of mothers with mood symptoms during pregnancy were 82% more likely of
      presenting psychiatric disorders than children of mothers that did not (1.82;
      1.48-2.25); and the chance of having mental disorders among children whose
      mothers had positive SRQ-20 at three months postpartum was 87% greater than the
      observed among children whose mothers had it negative (1.87; 1.50-2.33).
      LIMITATIONS: Because maternal anxiety/depression may interfere with
      interpretation of the child behavior, child's mental health being obtained by
      interviewing the mother is a limitation of this study. Lack of information on
      other risk factors may have lead to residual confounding on the effect of
      maternal mood symptoms at three months postpartum. CONCLUSIONS: Children of
      mothers presenting mood symptoms during pregnancy and in the first months
      postpartum are more likely to present psychiatric disorders at 6 years of age.

PMID- 24856565
TI  - Trauma type affects recognition of Post-Traumatic Stress Disorder among online
      respondents in the UK and Ireland.
AB  - BACKGROUND: Mental Health Literacy (MHL) predicts help-seeking for mental health
      difficulties. Public surveys show high recognition of Post-Traumatic Stress
      Disorder (PTSD) in relation to military contexts, but this has not been
      investigated with other sources of trauma. METHODS: A self-selecting sample of
      2960 participants from UK and Ireland completed an online survey. Participants
      viewed one of three vignettes that described either a male or female character
      experiencing identical PTSD symptoms, that differed only by trauma source
      (military combat, industrial accident, sexual assault). Participants were asked
      to state i) whether a mental health problem was being experienced, ii) what it
      was, and iii) what help should be sought. RESULTS: Trauma type was a key
      predictor of classification as a mental health problem, correct identification of
      PTSD, and help-seeking suggestions. For participants shown the military scenario
      the odds of recognising PTSD were 5.2 times higher than for those shown the
      sexual assault vignette, and 2.2 times higher than for those shown the accident
      scenario. Age (younger), gender (female), education (university), and personal
      mental health experience were additional significant predictors of higher
      recognition of PTSD. LIMITATIONS: Reasons for failing to recognise a mental
      health problem/PTSD were not explored. The online convenience sampling method may
      limit generalisability of results. CONCLUSIONS: Recognition of PTSD is
      significantly affected by trauma source. The data confirmed the pervasive
      association with military combat and suggest under-recognition of PTSD from other
      traumas, particularly sexual assault. Awareness campaigns may aim to increase MHL
      of PTSD from diverse trauma sources.

PMID- 24856566
TI  - Longitudinal course of cognitive deficits in bipolar disorder: a meta-analytic
      study.
AB  - OBJECTIVE: Persistent cognitive deficits in bipolar disorder represent a major
      impediment to functional adjustment, but their static or progressive nature
      remains to be ascertained. The aim of this study was to synthesize findings from
      longitudinal research in order to examine the trajectory of cognitive impairment
      in bipolar disorder. METHOD: A literature search was conducted through online
      databases covering the period between January 1990 and February 2014. Two
      approaches were undertaken. First, the results of longitudinal studies including
      neuropsychological assessment of stable bipolar patients at baseline and after a
      follow-up period of at least one year were meta-analyzed so as to obtain overall
      test-retest effect sizes for neurocognitive domains. Second, meta-analysis was
      restricted to longitudinal studies of bipolar patients including a control group.
      Patients' and controls' overall test-retest effect sizes were compared. RESULTS:
      Bipolar patients' performance on 14 cognitive measures remained stable after a
      mean follow-up period of 4.62 years. When meta-analysis was restricted to
      controlled studies, no patient-control differences were found regarding
      longitudinal cognitive outcomes. LIMITATIONS: Test-retest differences for
      medication variables and mood state could not be controlled. Sufficient data were
      not available to investigate a wider array of neuropsychological domains.
      Furthermore, most primary studies included relatively short test-restest
      intervals. CONCLUSION: To date, the available evidence from longitudinal studies
      is not in accordance with the hypothesis of a progressive nature of cognitive
      deficits in BD. The implications of this finding for further research are
      discussed.

PMID- 24856567
TI  - A genetically informed test of cholesterol levels and self-control, depressive
      symptoms, antisocial behavior, and neuroticism.
AB  - BACKGROUND: Low cholesterol levels have been found to be associated with a wide
      range of behavioral problems, including violent and criminal behavior, and a wide
      range of psychological problems including impulsivity, depression, and other
      internalizing problems. The casual mechanisms underlying these associations
      remain largely unknown, but genetic factors may play a role in the etiology of
      such associations as previous research has found significant genetic influence on
      cholesterol levels and various deleterious behavioral and psychological outcomes.
      The current study addressed this existing gap in the literature by performing a
      genetically sensitive test of the association between cholesterol levels and
      various outcomes including levels of self-control, depressive symptoms, anger
      expression, and neuroticism. METHODS: DeFries-Fulker (DF) analysis was used to
      analyze data from 388 twin pairs nested within the Survey of Midlife Development
      in the United States (MIDUS). RESULTS: The results of the genetically informed
      models revealed that high-density lipoprotein (HDL) cholesterol levels were
      negatively and significantly associated with depressive symptoms, had a
      marginally significant effect on neuroticism, and a nonsignificant effect on both
      anger expression and self-control. LIMITATIONS: The findings may not extrapolate
      to the larger population of American adults since the subsample of twins with
      cholesterol information may not be nationally representative. CONCLUSIONS:
      Genetic influences play a significant role in the association between cholesterol
      levels and various deleterious outcomes and failing to control for these
      influences may result in model misspecification and may increase the probability
      of detecting a significant association when one does not actually exist.

PMID- 24856568
TI  - Bipolar and panic disorders may be associated with hereditary defects in the
      innate immune system.
AB  - BACKGROUND: Mannan-binding lectin (MBL) and mannan-binding lectin-associated
      serine protease-2 (MASP-2) represent important arms of the innate immune system,
      and different deficiencies may result in infections or autoimmune diseases. Both
      bipolar and panic disorders are associated with increased inflammatory response,
      infections and mutual comorbidity. However, associations with MBL, MASP-2 or the
      gene, MBL2, coding for MBL, have not been investigated thoroughly. METHODS: One
      hundred patients with bipolar disorder, 100 with panic disorder and 349 controls
      were included. Serum concentrations of MBL and MASP-2 were measured and seven
      single nucleotide polymorphisms (SNPs) influencing these concentrations were
      genotyped. Disease association with genetic markers and serum levels were
      investigated. RESULTS: In panic disorder, we observed a large proportion (30%) of
      MBL deficient (<100ng/ml) individuals and significantly lower levels of MBL and
      MASP-2 plus association with the MBL2 YA two-marker haplotype. Bipolar disorder
      was associated with the MBL2 LXPA haplotype and lower MASP-2 levels. LIMITATIONS:
      No information on course or severity of disorders was included, and only MBL and
      MASP-2 were measured, excluding other components from the complement pathway.
      Restrictions defined by ethnical committees preclude information of control's
      ethnic origin. CONCLUSIONS: Significant differences in MBL and MASP-2
      concentrations were observed between cohorts, especially an intriguing finding
      associating panic disorder with MBL deficiency. These differences could not be
      fully explained by allele or haplotype frequency variations. Since MBL deficiency
      is highly heterogeneous and associated with both infectious and autoimmune
      states, more research is needed to identify which complement pathway components
      could be associated with bipolar respectively panic disorder.

PMID- 24856569
TI  - Efficacy and acceptability of group cognitive behavioral therapy for depression:
      a systematic review and meta-analysis.
AB  - BACKGROUND: Despite treatment guidelines for depression placing group cognitive
      behavioral therapy (group CBT) between low- and high-intensity evidence-based
      psychological interventions, the validity of the placement remains unknown. We
      aimed to systematically review evidence for the efficacy and acceptability of
      group CBT in patients with depression compared to four intensity levels of
      psychosocial interventions. METHODS: We searched the Cochrane Central Register of
      Controlled Trials, MEDLINE, PsycINFO, and Web of Science and hand-searched the
      references in identified publications. We selected randomized controlled trials
      comparing group CBT with four levels of interventions for adult patients with
      depression. Two authors independently assessed risk of bias. RESULTS: From 7953
      records, we identified 35 studies that compared group CBT to non-active (k=30),
      low-intensity (k=2), middle-intensity (k=8), and high-intensity (k=1)
      interventions. Group CBT had a superior efficacy (standardized mean difference
      [SMD]=-0.68) and a similar acceptability compared to non-active controls. Pooled
      results showed a small but non-significant excess of group CBT relative to middle
      intensity interventions (SMD=-0.21). LIMITATIONS: Over 60% of studies did not
      report enough information to judge selection and selective reporting bias.
      CONCLUSIONS: These results suggest the need for high-quality trials of group CBT
      compared to low- and high-intensity interventions.

PMID- 24856570
TI  - Association of subsyndromal and depressive symptoms with inflammatory markers
      among different ethnic groups: the multi-ethnic study of atherosclerosis (MESA).
AB  - OBJECTIVE: Depressive symptoms are associated with inflammation yet the
      association between inflammation and different levels of depression remains
      unclear. Therefore, we studied the association of subsyndromal and depressive
      symptoms with inflammatory markers in a large multi-ethnic cohort. METHODS: C
      reactive protein (CRP) (n=6269), interleukin-6 (IL-6) (n=6135) and tumor necrosis
      factor-alpha (TNF-alpha) (n=1830) were measured in selected participants from the
      multi-ethnic study of atherosclerosis (MESA). Subsyndromal depressive symptoms
      were defined as a CES-D value from 8 to 15, depressive symptoms as a CES-D>=16
      and normal as a CES-D<=7. Depressive states (subsyndromal and depressed) were
      entered into multivariable linear regression models incrementally adjusting for
      demographic, behavioral, biologic and comorbidities. RESULTS: Among 6289
      participants not taking antidepressants and free from CVD, the mean age was 62.2,
      while 52% were women, 36.4% were Caucasian, 28.9% African-American, 22.3%
      Hispanics and 12.4% Chinese-American. Of the total, 24.2% had subsyndromal
      depression and 11.8% had depressive symptoms. Compared to the non-depressed group
      and after controlling for demographics, there was no association between both
      subsyndromal and depressive symptoms with logCRP (beta=-0.01, p=0.80 and beta=
      0.05, p=0.25 respectively), logIL-6 (beta=0.01, p=0.71 and beta=-0.04, p=0.07
      respectively) and logTNF-alpha (beta=-0.03, p=0.29 and beta=0.06, p=0.18
      respectively). Moreover, fully adjusted models showed no significant associations
      for logIL-6 and logTNF-alpha and the different depressive categories. However,
      with full adjustment, we found a significant inverse association between
      depressive symptoms and lnCRP (beta=-0.10, p=0.01) that was not present for
      subsyndromal depression (beta=-0.05, p=0.11). CONCLUSION: Among participants not
      taking anti-depressants, subsyndromal depression is not associated with
      inflammation. However, depressive symptoms measured by CES-D>=16 are associated
      with a lower inflammation (CRP).

PMID- 24856571
TI  - A clinical trial of cranial electrotherapy stimulation for anxiety and comorbid
      depression.
AB  - BACKGROUND: Anxiety disorders are among the most prevalent mental disorders and
      are usually treated with medication and/or psychotherapy. When anxiety disorders
      are accompanied with comorbid depression, this further complicates the treatment
      process. Medication compliance is a common problem due to adverse side effects
      and new and effective treatments that have minimal side effects are needed for
      the treatment of anxiety and depression. This study used a randomized, double
      blind, sham controlled design to examine the effectiveness of CES as a treatment
      for anxiety disorders and comorbid depression in a primary care setting. The
      study was registered at clinicaltrials.gov, NCT01533415. METHODS: One hundred and
      fifteen participants, age 18 years and over, with a primary diagnosis of an
      anxiety disorder were enrolled from February 2012 to December 2012 The Hamilton
      Rating Scale for Anxiety (HAM-A) and the Hamilton Depression Rating Scale17 (HAM
      D17) were used for baseline and outcome measures at weeks one, three, and five.
      Response to treatment was defined as a reduction of >=50% or more on these
      measures. RESULTS: Analysis of covariance revealed a significant difference
      between the active CES group and the sham CES group on anxiety (p=0.001, d=0.94)
      and on depression (p=0.001, d=0.78) from baseline to endpoint of study in favor
      of the active CES group. CONCLUSIONS: CES significantly decreases anxiety and
      comorbid depression. Subjects reported no adverse events during the study.

PMID- 24856572
TI  - Cytoplasmic PAR-3 protein expression is associated with adverse prognostic
      factors in clear cell renal cell carcinoma and independently impacts survival.
AB  - Clear cell renal cell carcinomas (ccRCCs) represent 70% of renal cancers, and
      several clinical and histolopathological factors are implicated in their
      prognosis. We recently demonstrated that the overexpression of PAR-3 protein
      encoded by the PARD3 gene could be implicated in renal oncogenesis. The object of
      this work was to study the association of intratumoral PAR-3 expression with
      known prognostic parameters and clinical outcome. In this aim, PAR-3 expression
      was assessed by immunohistochemistry in ccRCC tumors of 101 patients from 2003 to
      2005. The immunostaining of PAR-3 was scored either as membranous (mPAR-3) or as
      both membranous and cytoplasmic (cPAR-3). Cytoplasmic PAR-3 was significantly
      associated with worse histopathological and clinical prognostic factors: Fuhrman
      grades 3 and 4, tumor necrosis, sarcomatoid component, adrenal invasion, renal
      and hilar fat invasion, eosinophilic component, a noninactivated VHL gene, higher
      tumor grade, lymph node involvement, metastasis, and worse clinical Eastern
      Cooperative Oncology Group and S classification scores. After multivariate
      analysis, 2 parameters were independently associated with cPAR-3: necrosis and
      eosinophilic components. In addition, cPAR-3 patients had shorter overall and
      progression-free survivals independently from strong prognostic validated factors
      like metastases. A cytoplasmic expression of PAR-3 is therefore implicated in
      worse clinical and pathological cancer features in ccRCC and could be useful to
      identify patients with high-risk tumors. 

PMID- 24856574
TI  - Splenic rupture associated with primary CMV infection, AMSAN, and IVIG.
AB  - Splenic rupture is a rare complication of primary cytomegalovirus infection, but
      has not been reported after administration of intravenous immunoglobulin or in
      the setting of the Guillain-Barre syndrome and its many variants, which often
      lead to treatment with intravenous immunoglobulin. There is strong evidence that
      intravenous immunoglobulin causes sequestration of erythrocytes in the spleen and
      extravascular hemolytic anemia. This may result in a two-hit scenario that
      clinicians should be aware of, where a patient who is at risk for splenic rupture
      due to primary cytomegalovirus infection receives intravenous immunoglobulin as
      treatment for the cytomegalovirus-associated Guillain-Barre syndrome, further
      increasing their risk of rupture. 

PMID- 24856573
TI  - Glomerular epithelial cell phenotype in diffuse mesangial sclerosis: a report of
      2 cases with markedly increased urinary podocyte excretion.
AB  - We report 2 cases of diffuse mesangial sclerosis (DMS) accompanied by severe
      podocyte excretion in urine. Patient 1 was a 9-day-old girl with a WT1 mutation
      who developed Wilms tumor at 6 months of age and was subsequently diagnosed with
      Denys-Drash syndrome. Patient 2 was a 1-year-old boy without a WT1 abnormality
      but presenting with heavy proteinuria. In both patients, histological examination
      showed findings of DMS. Immunohistochemical staining for synaptopodin (a podocyte
      marker) revealed a reduced number of podocytes in the glomeruli with severe
      sclerosis; however, podocytes persisted in the relatively intact glomeruli. Some
      glomeruli were accompanied by sclerotic lesions surrounded by proliferating
      cells; immunofluorescence staining revealed a majority of these proliferating
      cells to be positive for claudin-1 (a parietal cell marker) but negative for
      synaptopodin. These findings suggest that podocyte loss and the consequent
      proliferation of parietal cells are common processes in the pathogenesis of DMS.

PMID- 24856575
TI  - Percutaneous nephrolithotomy in the oblique supine lithotomy position and prone
      position: a comparative study.
AB  - OBJECTIVES: To compare the safety, efficacy, and complications of percutaneous
      nephrolithotomy (PCNL) in the oblique supine lithotomy position vs the prone
      position in a randomized comparative study. PATIENTS AND METHODS: The study
      included 101 and 102 patients in the oblique supine lithotomy position and prone
      position, respectively. Inclusion criteria were renal and upper ureteral stones.
      Exclusion criteria were uncorrectable bleeding disorders, active urinary tract
      infection, and pregnancy. RESULTS: Both the groups were comparable regarding the
      male/female ratio, stone size, and site. No significant differences were found in
      terms of the stone-free rate, blood transfusion rate, and complication rates.
      Significant differences were reported in mean hemoglobin loss (-1.03 and -2.18
      g/dL), mean operative time (86.16 and 111.7 minutes), and mean hospital stay
      (49.88 and 81.2 hours) in the supine and prone positions, respectively, and
      anesthesiological parameters (the mean blood pressure decreased by 2 and 14.06 mm
      Hg, the mean heart rate changed by -0.82 and +13.28 beat/minute, and the peak air
      way pressure changed by +1.08 cm H2O and +7.56 cm H2O in the supine and prone
      positions, respectively). CONCLUSIONS: PCNL in both positions was equally
      successful with no significant differences in complications. PCNL in the oblique
      supine lithotomy position was superior to PCNL in the prone position regarding
      operative time, hospital stay, and effects on respiratory and cardiovascular
      status, making it more comfortable for patients and anesthesiologists. Morbidly
      obese patients, patients with cardiologic disorders, and patients with pulmonary
      obstructive airway disease need further studies to show if they would benefit
      from these differences. Additionally, it is more comfortable for the surgeon with
      little challenges added in the initial puncture.

PMID- 24856576
TI  - Differential activities of fungi-derived tannases on biotransformation and
      substrate inhibition in green tea extract.
AB  - Tannases are important enzymes in the antioxidant potential of tea leaves. In
      this study, we evaluated the effect of two tannases (T1 and T2) on
      biotransformation of tea polyphenols and antioxidative activities from catechins
      in green tea extract (GTE). The T1 tannase-catalyzed reaction was inhibited by
      the addition of >2.0% GTE substrate, whereas the T2-catalyzed reaction was not
      inhibited, even by addition of 5.0% GTE. Furthermore, the T1 tannase-catalyzed
      reaction was inhibited by addition of 10 mg mL(-1) EGCG, whereas the T2 tannase
      catalyzed reaction did not display any inhibitory effect. These results indicate
      that T2 tannase was more tolerant than T1 tannase to substrate inhibition in
      degallation reactions. Specifically, the substrate EGCG (90,687.1 MUg mL(-1)) was
      transformed into gallic acid (50,242.9 MUg mL(-1)) and EGC (92,598.3 MUg mL(-1))
      after 1-h treatment with T2 tannase (500 U g(-1)). The tannase-mediated product
      displayed higher in vitro radical-scavenging activity than the control. IC50
      value of GTE on ABTS and DPPH radicals (46.1 MUg mL(-1) and 18.4 MUg mL(-1),
      respectively) decreased markedly after T2 tannase treatment (to 35.8 MUg mL(-1)
      and 15.1 MUg mL(-1), respectively). These results indicate that T2 tannase
      treatment of GTE enhanced its radical-scavenging activity, an increase that was
      also observed in the reaction using EGCG substrate. Taken together, our results
      revealed that T2 tannase is more suitable for biotransformation of catechins in
      GTE than T1 tannase, and T2 treatment provides an enhanced radical-scavenging
      effect. 

PMID- 24856578
TI  - Implications for patient safety in the use of safe patient handling equipment: a
      national survey.
AB  - BACKGROUND: The prevalence of musculoskeletal injuries among nursing staff has
      been high due to patient handling and movement. Internationally, healthcare
      organizations are integrating technological equipment into patient handling and
      movement to improve safety. Although evidence shows that safe patient handling
      programs reduce work-related musculoskeletal injuries in nursing staff, it is not
      clear how safe these new programs are for patients. OBJECTIVES: The objective of
      this study was to explore adverse patient events associated with safe patient
      handling programs and preventive approaches in US Veterans Affairs medical
      centers. METHODS: The study surveyed a convenience sample of safe patient
      handling program managers from 51 US Department of Veterans Affairs medical
      centers to collect data on skin-related and fall-related adverse patient events.
      RESULTS: Both skin- and fall-related adverse patient events associated with safe
      patient handling occurred at VA Medical centers. Skin-related events included
      abrasions, contusions, pressure ulcers and lacerations. Fall-related events
      included sprains and strains, fractures, concussions and bleeding. Program
      managers described contextual factors in these adverse events and ways of
      preventing the events. CONCLUSIONS: The use of safe patient handling equipment
      can pose risks for patients. This study found that organizational factors, human
      factors and technology factors were associated with patient adverse events. The
      findings have implications for how nursing professionals can implement safe
      patient handling programs in ways that are safe for both staff and patients.

PMID- 24856579
TI  - Distribution of Lutzomyia ayacuchensis, the vector of Andean-type cutaneous
      leishmaniasis, at different altitudes on the Andean slope of Ecuador.
AB  - Distribution of the vector species is a major risk factor for the endemicity of
      leishmaniasis. In the present study, the vertical distribution of Lutzomyia (Lu.)
      ayacuchensis, the vector of Leishmania (Leishmania) mexicana in the Ecuadorian
      Andes, was surveyed at different altitudes (300-2500m above sea level) of the
      Andean slope. The vector species Lu. ayacuchensis was identified at an altitude
      of 650m and a higher areas, and higher distribution ratio of the species was
      observed at higher altitudes. In addition, high ratios of L. (L.) mexicana
      infection were detected in higher areas, but none in lower populations of sand
      flies. Since an association between sand fly populations and vector competence is
      suggested in Lu. ayacuchensis, haplotype analysis was performed on the species
      from different altitudes of the study areas; however, no apparent difference was
      observed among populations. These results suggested that Lu. ayacuchensis in
      Andean slope areas of Ecuador has the potential to transmit L. (L.) mexicana and
      spread leishmaniasis in these areas. 

PMID- 24856577
TI  - A novel alternative to environmental monitoring to detect workers at risk for
      beryllium exposure-related health effects.
AB  - The purpose of this study was to describe a methodology for surveillance and
      monitoring of beryllium exposure using biological monitoring to complement
      environmental monitoring. Eighty-three Israeli dental technicians (mean age 41.6
      +/- 1.36 years) and 80 American nuclear machining workers (54.9 +/- 1.21 years)
      were enrolled. Biological monitoring was carried out by analyzing particle size
      (laser technique) and shape (image analysis) in 131/163 (80.3%) induced sputum
      samples (Dipa Analyser, Donner Tech, Or Aquiva, Israel). Environmental monitoring
      was carried out only in the United States (Sioutas impactor, SKC, Inc., Eighty
      Four, Pa.). Pulmonary function testing performance and induced sputum retrieval
      were done by conventional methods. Sixty-three Israeli workers and 37 American
      workers were followed up for at least 2 years. Biological monitoring by induced
      sputum indicated that a >92% accumulation of <5 MUm particles correlated
      significantly to a positive beryllium lymphocyte proliferation test result (OR
      3.8, 95% CI 1.2-11.4, p = 0.015) among all participants. Environmental monitoring
      showed that beryllium particles were <1 MUm, and this small fraction (0.1-1 MU)
      was significantly more highly accumulated in nuclear machining workers compared
      to dental technicians. The small fractions positively correlated with induced
      sputum macrophages (r = 0.21 p = 0.01) and negatively correlated with diffusion
      lung carbon monoxide single breath (DLCO-SB r = 0.180 p = 0.04) in all subjects.
      Years of exposure were positively correlated to the number of accumulated
      particles 2-3 MU in diameter (r = 0.2, p = 0.02) and negatively correlated to
      forced expiratory volume in one second/forced vital capacity findings (r = -0.18,
      p = 0.02). DLCO was decreased in both groups after two years of monitoring.
      Biological monitoring is more informative than environmental monitoring in the
      surveillance and monitoring of workers in beryllium industries. Induced sputum is
      a feasible and promising biomonitoring method that should be included in the
      surveillance of exposed workers.

PMID- 24856580
TI  - A systematic review and meta-analysis of psychotherapy for late-life depression.
AB  - OBJECTIVES: To determine the efficacy of psychotherapy in late-life depression
      and to determine the effect of the type of control group on the magnitude of
      psychotherapy effects. DESIGN: A systematic review and meta-analysis of
      randomized controlled psychotherapy trials for late-life depression. SETTING:
      Outpatient clinics or in subjects' home. PARTICIPANTS: Subjects aged 55 years or
      older with acute-phase depressive disorder. MEASUREMENTS: Change in depressive
      symptoms was measured with validated scales. Standardized mean differences (SMD)
      were calculated for each therapy-control contrast, as meta-analytic summaries for
      contrasts using a similar control, and for all contrasts combined. RESULTS: The
      search identified 27 trials with 37 therapy-control contrasts and 2,245 subjects.
      Trials utilized five types of control groups (waitlist, treatment-as-usual,
      attention, supportive therapy, placebo). In the combined contrasts, psychotherapy
      was effective (SMD: 0.73; 95% confidence interval [CI]: 0.51, 0.95; z=6.42,
      p<0.00001). The SMD varied widely (from 0.05 to 1.36) and significantly
      (chi2=35.67, df=4, p<0.00001) between subgroups by type of control. In five
      trials that compared psychotherapy with supportive therapy, the SMD was 0.39 (95%
      CI: 0.16, 0.61; z=3.37, p<0.0007; I2=0%). The SMD was 0.11 within the waitlist
      controls and 1.10 within the supportive therapy subgroup. CONCLUSIONS:
      Psychotherapy is effective for late-life depression, but the magnitude of the
      effect varies widely with the type of control group. Supportive therapy appears
      to best control for the nonspecific elements of psychotherapy and is associated
      with considerable change itself, but few trials have utilized it as a control.

PMID- 24856582
TI  - Compassion: the missing link in quality of care.
AB  - This article discusses the impact of selected findings from a PhD-study that
      focuses on compassion as a guiding principle for contemporary nursing education
      and practice. The study, of which the literature review and empirical findings
      have already been published, looked at compassion as perceived within the
      relationship of nurses and older persons with a chronic disease. The patient
      group was chosen because daily life for them is characterized by long-term
      dependency on care. The literature review resulted in a theoretical framework of
      compassion that also explores other closely related concepts such as suffering
      and empathy. The empirical part of the study, in which 61 in-depth interviews and
      6 group interviews with patients and nurses took place, showed that compassion is
      a mirroring process in response to grief. Compassion consists of seven dimensions
      such as attentiveness and presence, in which saliency, so as to anticipate
      patients' needs, is of major importance. Compassion is perceived by participants
      as an indispensable aspect of care, which helps to reveal relevant information in
      order to establish appropriate outcomes of care. This article focuses on the
      aspects of the PhD-study in which an analysis of compassion in the context of
      both modern as well as the history of nursing took place. Currently evidence
      based practice is regarded as the standard for good quality care. Nevertheless
      there is an on-going debate about what constitutes good quality care. Within this
      debate two opposing views are apparent. One view defines good care as care
      supported by the best scientific evidence. The other view states that good care
      takes place within the nurse-patient relationship in which the nurse performs
      professional care based on intuitive knowing. It is suggested that compassion is
      the (missing) link between these views. 

PMID- 24856581
TI  - Alexithymia impairs the cognitive control of negative material while facilitating
      the recall of neutral material in both younger and older adults.
AB  - We investigated the moderating impact of the personality construct alexithymia on
      the ability of younger and older adults to control the recall of negative and
      neutral material. We conducted two experiments using the directed forgetting
      paradigm with younger and older adults. Participants studied negative (Experiment
      1) or neutral (Experiment 2) words. Participants were instructed to forget the
      first half and remember the second half of an entire list of words. Overall, we
      found that alexithymia impairs the ability of both younger and older adults to
      cognitively control negative material (through both recall and inhibition). The
      "externally oriented thinking" factor of alexithymia appears to play a
      particularly pertinent role in terms of inhibiting negative material.
      Furthermore, older adults recalled fewer sought after negative items, but this
      was not evident in terms of inhibition. In contrast, only age (older adults)
      negatively impacted the recall of sought after neutral items. Interestingly,
      alexithymia had the opposite effect: the "difficulty in identifying emotions"
      factor of alexithymia was associated with an increased recall of neutral items.
      We discuss these results in terms of alexithymia and its impact on cognitive
      control. 

PMID- 24856583
TI  - A national study of selection processes for student nurses and midwives.
AB  - BACKGROUND: This paper presents the main findings from a project that aimed to
      evaluate selection processes for the recruitment of student nurses and midwives.
      OBJECTIVES: The main objectives were to: Design The evaluation was designed
      principally to achieve explanation, with multiple case study methodology adopted
      as the main approach. Within this ambit mixed methods of data collection
      involving questionnaires and interviews were used. Participants Seven of the
      Scotland-based Higher Education Institutions participated in the research, with
      participation from Admissions Tutors, clinical interviewers, academic
      interviewers, and students. METHODS: The methods included: a scoping
      questionnaire with follow-on questionnaire to elicit views on the strengths and
      limitations of chosen selection processes; interviews and focus groups to build
      on these findings. Analytical approaches were congruent with the chosen data
      collection approaches. Findings HEIs typically have rationales for their various
      chosen approaches to selection. However, our findings indicate that there is a
      lack of evidence for most selection approaches particularly in relation to
      interviewing. There is a growing evidence-base for the use of multiple mini
      interviews, and emotional intelligence testing. CONCLUSIONS: There is a need to
      work collectively cross-UK to bring together the evidence-base around selection
      so that processes and decision-making are as valid, reliable, effective and
      transparent as possible.

PMID- 24856584
TI  - Cecal succinate elevated by some dietary polyphenols may inhibit colon cancer
      cell proliferation and angiogenesis.
AB  - This study demonstrated that 0.5% dietary rutin, ellagic acid, or curcumin
      markedly increased cecal succinate levels in rats fed a high-fat diet, whereas
      catechin, caffeic acid, and quercetin did not. Other organic acids were modestly
      or hardly affected by polyphenols. To clarify the effects of succinate levels
      increased by polyphenols, this study examined the effects of succinate on the
      growth and proliferation of colon cancer cells and angiogenesis. The growth and
      proliferation of HT29 human colon cancer cells and angiogenesis in an ex vivo
      model were significantly inhibited by succinate at a dose close to that in the
      cecum of rats fed polyphenols. Furthermore, succinate inhibited the migration of
      human umbilical vein endothelial cells. These findings suggest that the
      consumption of some polyphenols affects the health and diseases of the large
      intestine by elevating succinate. 

PMID- 24856588
TI  - Conversion of activated-sludge reactors to microbial fuel cells for wastewater
      treatment coupled to electricity generation.
AB  - Wastewater can be treated in microbial fuel cells (MFCs) with the aid of microbes
      that oxidize organic compounds using anodes as electron acceptors. Previous
      studies have suggested the utility of cassette-electrode (CE) MFCs for wastewater
      treatment, in which rice paddy-field soil was used as the inoculum. The present
      study attempted to convert an activated-sludge (AS) reactor to CE-MFC and use
      aerobic sludge in the tank as the source of microbes. We used laboratory-scale (1
      L in capacity) reactors that were initially operated in an AS mode to treat
      synthetic wastewater, containing starch, yeast extract, peptone, plant oil, and
      detergents. After the organics removal became stable, the aeration was
      terminated, and CEs were inserted to initiate an MFC-mode operation. It was
      demonstrated that the MFC-mode operation treated the wastewater at similar
      efficiencies to those observed in the AS-mode operation with COD-removal
      efficiencies of 75-80%, maximum power densities of 150-200 mW m(-2) and Coulombic
      efficiencies of 20-30%. These values were similar to those of CE-MFC inoculated
      with the soil. Anode microbial communities were analyzed by pyrotag sequencing of
      16S rRNA gene PCR amplicons. Comparative analyses revealed that anode communities
      enriched from the aerobic sludge were largely different from those from the soil,
      suggesting that similar reactor performances can be supported by different
      community structures. The study demonstrates that it is possible to construct
      wastewater-treatment MFCs by inserting CEs into water-treatment tanks. 

PMID- 24856586
TI  - Depletion of carcinoma-associated fibroblasts and fibrosis induces
      immunosuppression and accelerates pancreas cancer with reduced survival.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is associated with marked fibrosis and
      stromal myofibroblasts, but their functional contribution remains unknown.
      Transgenic mice with the ability to delete alphaSMA(+) myofibroblasts in
      pancreatic cancer were generated. Depletion starting at either noninvasive
      precursor (pancreatic intraepithelial neoplasia) or the PDAC stage led to
      invasive, undifferentiated tumors with enhanced hypoxia, epithelial-to
      mesenchymal transition, and cancer stem cells, with diminished animal survival.
      In PDAC patients, fewer myofibroblasts in their tumors also correlated with
      reduced survival. Suppressed immune surveillance with increased CD4(+)Foxp3(+)
      Tregs was observed in myofibroblast-depleted mouse tumors. Although myofibroblast
      depleted tumors did not respond to gemcitabine, anti-CTLA4 immunotherapy reversed
      disease acceleration and prolonged animal survival. This study underscores the
      need for caution in targeting carcinoma-associated fibroblasts in PDAC. 

PMID- 24856589
TI  - Biochemical characterization of Aspergillus oryzae native tannase and the
      recombinant enzyme expressed in Pichia pastoris.
AB  - In this study, the biochemical properties of the recombinant tannase from
      Aspegillus oryzae were compared with those of the native enzyme. Extracellular
      native tannase was purified from a commercial enzyme source. Recombinant tannase
      highly expressed in Pichia pastoris was prepared as an active extracellular
      protein. Purified native and recombinant tannases produced smeared bands with
      apparent molecular masses of 45-80 kDa and 45-75 kDa, respectively, by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis. After N-deglycosylation, the
      native enzyme yielded molecular masses of 33 kDa and 30 kDa, whereas the
      recombinant enzyme yielded molecular masses of 34 kDa and 30 kDa. Purified native
      and recombinant tannases had an optimum pH of 4.0-5.0 and 5.0, respectively, and
      were stable up to 40 degrees C. After N-deglycosylation, both enzymes exhibited
      reduced thermostability. Catalytic efficiencies of both purified enzymes were
      greater with natural substrates, such as (-)-catechin, (-)-epicatechin, and (-)
      epigallocatechin gallates, than those with synthetic substrates, such as methyl,
      ethyl, and propyl gallates. However, there were no activities against the methyl
      esters of ferulic, p-coumaric, caffeic, and sinapic acids, which indicate
      feruloyl esterase activity, or the ethyl, propyl, and butyl esters of 4
      hydroxybenzoic acid, which indicate paraben hydrolase activity. 

PMID- 24856587
TI  - Sustained reduction of central line-associated bloodstream infections outside the
      intensive care unit with a multimodal intervention focusing on central line
      maintenance.
AB  - BACKGROUND: Central venous catheter use is common outside the intensive care
      units (ICUs), but prevention in this setting is not well studied. We initiated
      surveillance for central line-associated bloodstream infections (CLABSIs) outside
      the ICU setting and studied the impact of a multimodal intervention on the
      incidence of CLABSIs across multiple hospitals. METHODS: This project was
      constructed as a prospective preintervention-postintervention design. The project
      comprised 3 phases (preintervention [baseline], intervention, and
      postintervention) over a 4.5-year period (2008-2012) and was implemented through
      a collaborative of 37 adult non-ICU wards at 6 hospitals in the Rochester, NY
      area. The intervention focused on engagement of nursing staff and leadership,
      nursing education on line care maintenance, competence evaluation, audits of line
      care, and regular feedback on CLABSI rates. Quarterly rates were compared over
      time in relation to intervention implementation. RESULTS: The overall CLABSI rate
      for all participating units decreased from 2.6/1000 line-days preintervention to
      2.1/1,000 line-days during the intervention and to 1.3/1,000 line-days
      postintervention, a 50% reduction (95% confidence interval, .40-.59) compared
      with the preintervention period (P .0179). CONCLUSION: A multipronged approach
      blending both the adaptive and technical aspects of care including front line
      engagement, education, execution of best practices, and evaluation of both
      process and outcome measures may provide an effective strategy for reducing
      CLABSI rates outside the ICU.

PMID- 24856585
TI  - Stromal elements act to restrain, rather than support, pancreatic ductal
      adenocarcinoma.
AB  - Sonic hedgehog (Shh), a soluble ligand overexpressed by neoplastic cells in
      pancreatic ductal adenocarcinoma (PDAC), drives formation of a fibroblast-rich
      desmoplastic stroma. To better understand its role in malignant progression, we
      deleted Shh in a well-defined mouse model of PDAC. As predicted, Shh-deficient
      tumors had reduced stromal content. Surprisingly, such tumors were more
      aggressive and exhibited undifferentiated histology, increased vascularity, and
      heightened proliferation--features that were fully recapitulated in control mice
      treated with a Smoothened inhibitor. Furthermore, administration of VEGFR
      blocking antibody selectively improved survival of Shh-deficient tumors,
      indicating that Hedgehog-driven stroma suppresses tumor growth in part by
      restraining tumor angiogenesis. Together, these data demonstrate that some
      components of the tumor stroma can act to restrain tumor growth.

PMID- 24856590
TI  - Effective Rho-associated protein kinase inhibitor treatment to dissociate human
      iPS cells for suspension culture to form embryoid body-like cell aggregates.
AB  - Treatment conditions using Y-27632 in the preparation of cell suspension of
      dissociated human pluripotent stem cells (hiPSCs) were investigated in the
      context of embryoid body (EB)-like cell aggregates. The effectiveness of a
      pretreatment with Y-27632 before cell dissociation and that of a Y-27632
      treatment during cell dissociation were investigated from the viewpoint of
      simplicity and robustness. The duration of Y-27632 treatment in the preparation
      process affected the circularity and agglomeration of dissociated hiPSCs. A
      single application of pretreatment failed to prevent the onset of blebbing.
      However, a pretreatment promoted the agglomeration of dissociated hiPSCs when
      combined with the addition of Y-27632 to cell suspension. Our results indicate
      that pretreatment enhances the agglomeration potential of dissociated hiPSCs.
      When cell dissociation was performed in the presence of Y-27632, dissociated
      hiPSCs possessed the highest circularity and significant agglomerating property.
      It was shown that treatment with Y-27632 during cell dissociation is a simple and
      robust method to prepare dissociated hiPSCs for suspension culture to form EB
      like cell aggregates. 

PMID- 24856591
TI  - A population approach to disease management: hepatitis C direct-acting antiviral
      use in a large health care system.
AB  - BACKGROUND: The introduction of the first direct-acting antiviral agents (DAAs)
      for the treatment of hepatitis C virus (HCV), telaprevir and boceprevir, marked a
      unique event in which 2 disease-changing therapies received FDA approval at the
      same time. Comparative safety and effectiveness data in real-world populations
      upon which to make formulary decisions did not exist. OBJECTIVE: To describe the
      implementation, measurement, and outcomes of an enduring population-based
      approach of surveillance of medication management for HCV. METHODS: The
      foundation of the population approach to HCV medication management used by the
      Department of Veterans Affairs (VA) relied upon a basic framework of (a)
      providing data for effective regional and local management, (b) education and
      training, (c) real-time oversight and feedback from a higher organization level,
      and (d) prompt outcome sharing. These population-based processes spanned across
      the continuum of the direct-acting antiviral oversight process. We used the VA's
      HCV Clinical Case Registry-which includes pharmacy, laboratory, and diagnosis
      information for all HCV-infected veterans from all VA facilities-to assess DAA
      treatment eligibility, DAA uptake and timing, appropriate use of DAAs including
      HCV RNA monitoring and medication possession ratios (MPR), nonconcordance with
      guidance for adjunct erythropoiesis-stimulating agent (ESA) and granulocyte
      colony-stimulating factor (GCSF) use, hematologic adverse effects,
      discontinuation rates, and early and sustained virologic responses. Training
      impact was assessed via survey and change in pharmacist scope of practice.
      RESULTS: One year after FDA approval, DAAs had been prescribed at 120 of 130 VA
      facilities. Over 680 VA providers participated in live educational training
      programs including 380 pharmacists, and pharmacists with a scope of practice for
      HCV increased from 59 to 110 pharmacists (86%). HCV RNA futility testing improved
      such that only 1%-3% of veterans did not have appropriate testing compared with
      15%-17% 6 months earlier. By facility, the median proportion of veterans with MPR
      >= 0.95 remained 80% for those prescribed boceprevir; for telaprevir, the median
      proportion was 75% and improved to 80% 6 months later. Nonconcordance with VA
      medication guidance was as follows: receipt of an ESA without dose reducing
      ribavirin, 30% boceprevir, 45% telaprevir; ESA initiated with a hemoglobin
      greater than 10 g/dL, 42% boceprevir, 25% telaprevir; receipt of GCSF with
      absolute neutrophil count above the criteria threshold, 84%. CONCLUSIONS: This
      clinically focused, comprehensive, population-based medication management
      approach affected real-time change in health services, practice, and outcomes
      evidenced by widespread and rapid DAA uptake, improved HCV RNA monitoring,
      attention to adherence, and more appropriate management of DAA-related anemia.
      Timely outcome sharing provided decision makers and clinicians evidence to
      support current HCV practices.

PMID- 24856592
TI  - Medical and pharmacy coverage decision making at the population level.
AB  - Medicare is one of the largest health care payers in the United States. As a
      result, its decisions about coverage have profound implications for patient
      access to care. In this commentary, the authors describe how Medicare used
      evidence on heterogeneity of treatment effects to make population-based decisions
      on health care coverage for implantable cardiac defibrillators. This case is
      discussed in the context of the rapidly expanding availability of comparative
      effectiveness research. While there is a potential tension between population
      based and patient-centered decision making, the expanded diversity of populations
      and settings included in comparative effectiveness research can provide useful
      information for making more discerning and informed policy and clinical
      decisions. 

PMID- 24856593
TI  - The good, the bad, and the different: a primer on aspects of heterogeneity of
      treatment effects.
AB  - The concept of heterogeneity is concerned with understanding differences within
      and across patients and studies. Heterogeneity of treatment effects is nonrandom
      variability in response to treatment and includes both benefits and harms.
      Because not all patients respond the same way, treatment decisions applied in a
      "one size fits all" fashion based on the average response observed in clinical
      trials may lead to suboptimal outcomes for some patients. Variation in outcomes
      among patients may be caused by observable and nonobservable factors. Changes in
      patients' health status over time can contribute to variability among patients.
      Assuming that the results from clinical trials are homogeneous across patients
      may fail to take into account clinically significant variability where some
      patients may receive benefit and others harm. Subgroup analyses and prediction
      models are 2 tools to explain variability observed within a study. Evidence
      synthesis with meta-analysis can provide useful information on the overall
      effectiveness and response among groups of patients undersampled in individual
      studies. Yet caution is warranted if the meta-analysis is missing studies or the
      individual studies comprising the meta-analysis are inherently different.For
      those making clinical, coverage, and reimbursement decisions at a population
      level, such as clinicians and pharmacy and therapeutics committee members,
      understanding the variation among patients, among subpopulations or populations
      of patients, among clinical studies, or within a meta-analysis is important to
      ensuring optimal patient outcomes. This article presents a variety of tools and
      resources to aid decision makers as they evaluate the literature to determine
      when clinically relevant differences exist. 

PMID- 24856594
TI  - Managing heterogeneity in prescription drug coverage policies.
AB  - Necessity and fairness require that health plans limit the products and services
      they cover. The basis for these decisions refers to population averages and
      related population parameters. However, individuals vary and may not be
      accurately represented by the parameters used to establish coverage policies.
      Health plans, therefore, are obligated to anticipate and manage heterogeneity
      among their member groups. This commentary offers considerations for managing
      heterogeneity in prescription drug benefits. 

PMID- 24856595
TI  - Evaluation of an educational program on deciphering heterogeneity for medical
      coverage decisions.
AB  - BACKGROUND: It is increasingly important for decision makers, such as medical and
      pharmacy managers (or pharmacy therapeutics committee members and staff), to
      understand the variation and diversity in treatment response as decisions shift
      from an individual patient perspective to optimizing care for populations of
      patients. OBJECTIVE: To assess the effectiveness of an instructional program on
      heterogeneity designed for medical and pharmacy managers. METHODS: A live
      educational program was offered to members of the Academy of Managed Care
      Pharmacy at the fall 2012 educational meeting and also to medical directors and
      managers attending a national payer roundtable meeting in October 2012.
      Participants completed a retrospective pretest-posttest assessment of their
      knowledge, attitudes, and self-efficacy immediately following the program.
      Participants were offered the opportunity to participate in a follow-up
      assessment 6 months later. Willing participants for the follow-up assessment were
      contacted via e-mail and telephone. Rasch rating scale models were used to
      compare pre- and postscores measuring participants' knowledge about and attitude
      towards heterogeneity. RESULTS: A total of 49 individuals completed the
      retrospective pretest-posttest assessment and agreed to be a part of the program
      evaluation. Fifty percent (n = 25) of participants had heard of the phrase
      "heterogeneity of treatment effect," and 36 (72%) were familiar with the phrase
      "individualized treatment effect" prior to the live program. Participants
      reported a significant improvement in knowledge of heterogeneity (P  less than 
      0.01) and attitudes about heterogeneity (P  less than  0.01) immediately after
      attending the program. At the time of the educational program, participants had
      either never considered heterogeneity (26%) or reported not knowing (28%) whether
      their organizations considered it when determining basic coverage. Participants
      were more likely to report "sometimes" considering heterogeneity for determining
      necessity for individual appeals, prior authorization, tier placement for
      pharmaceutical therapies, and other types of medical management. At the 6-month
      follow-up, 21 of the 49 willing participants (43% response rate) completed the
      evaluation; participants continued to have a good understanding of heterogeneity,
      but there was no significant difference in attitudes towards heterogeneity
      between pre- and 6-month follow-up. CONCLUSION: A live educational program was
      effective in improving participants' immediate knowledge and attitudes regarding
      the topic of heterogeneity. Participating managed care pharmacists and medical
      managers indicated that heterogeneity of treatment effect was likely to be used
      in determining prior authorizations and determining necessity.

PMID- 24856596
TI  - Quitting patterns and predictors of success among participants in a tobacco
      cessation program provided by pharmacists in New Mexico.
AB  - BACKGROUND: Tobacco use causes hundreds of thousands of deaths in the United
      States each year. Pharmacists are available in the community to provide tobacco
      cessation interventions. Between 2004 and 2010, the New Mexico Pharmaceutical
      Care Foundation (NMPCF) provided a pharmacist-led tobacco cessation program to
      residents in New Mexico. OBJECTIVES: To (a) obtain point prevalence quit rates at
      1 month, 3 months, and 6 months follow-up for participants enrolled in the NMPCF
      program; (b) differentiate between the quitting patterns of enrolled
      participants; and (c) identify predictors associated with the quitting patterns.
      METHODS: Seven-year data were combined for the pattern analysis. Four quitting
      patterns were defined, including immediate quitters, delayed quitters, once
      quitters, and never quitters. Multinomial logistic regression was used to
      identify characteristics of participants with different quitting patterns.
      RESULTS: The analysis included 1,437 participants. The average point prevalence
      quit rate at 1 month, 3 months, and 6 months was 29.3%, 23.3%, and 18.0%,
      respectively. Based on our definition for quitting patterns, the study sample
      consisted of 145 (10.1%) immediate quitters, 113 (7.9%) delayed quitters, 298
      (20.7%) once quitters, and 881 (61.3%) never quitters. Multinomial logistic
      regression identified associations between quitting patterns and demographics,
      tobacco use and restrictions, baseline confidence in successful quitting, and
      pharmacotherapy aids used to quit. Relationships varied between quitting
      patterns. CONCLUSIONS: The study findings showed that having community
      pharmacists provide smoking cessation interventions resulted in quitting success
      rates similar to other health care professionals, which ranged from 9.9% to
      26.0%. Since pharmacists are a widely available resource for their patients,
      managed care organizations may be able to improve the health, and avoid
      subsequent tobacco-related adverse health outcomes, of their members by
      implementing a program similar to the NMPCF Tobacco Cessation Program.

PMID- 24856597
TI  - Association of out-of-pocket pharmacy costs with adherence to varenicline.
AB  - BACKGROUND: Varenicline, a nicotinic acetylcholine receptor partial agonist, is a
      pharmacotherapy indicated for smoking cessation treatment. To date, no research
      has examined the relationship between out-of-pocket (OOP) expense and varenicline
      adherence among Medicare beneficiaries. OBJECTIVES: To (a) characterize
      medication utilization patterns of varenicline among Medicare members newly
      initiated on varenicline and (b) examine the relationship between member OOP
      expense and varenicline medication adherence. METHODS: In this retrospective
      cohort study, pharmacy claims data were used to identify Medicare Advantage
      Prescription Drug Plan (MAPD) members newly initiated on varenicline. Demographic
      and clinical characteristics, varenicline medication utilization patterns, and
      pharmacy costs (total and varenicline-specific) were determined for members
      included in the study. Varenicline adherence was measured by calculating the
      proportion of days covered (PDC) over a period of 84 days (12 weeks) after
      initiation. Multiple regression analysis was used to examine the relationship
      between varenicline OOP cost and varenicline medication utilization, while
      controlling for sociodemographic characteristics, clinical factors, and
      nonvarenicline pharmacy costs. RESULTS: A total of 15,452 MAPD members were
      included in the analysis. Mean (SD) subject age was 62.6 (10.0) years; 21.1% (n =
      3,256) were dual eligible; and 33.0% (n = 5,106) received a low-income subsidy.
      Mean (SD) initial varenicline treatment episode duration was 50.8 (37.8) days,
      with a mean (SD) varenicline days' supply of 47.8 (32.6) obtained by members
      during the initial treatment episode. Mean (SD) PDC was 0.51 (0.24), and 14.9% (n
      = 2,302) of members were classified as adherent to treatment (PDC  >=  0.80).
      Greater varenicline OOP expense was significantly associated with lower PDC
      (regression coefficient = -0.058, P  less than  0.001) and significantly
      associated with lower odds of receiving a refill for varenicline (odds ratio
      0.594, 95% CI: 0.540-0.655, P  less than  0.001). CONCLUSIONS: Among Medicare
      beneficiaries newly initiated on varenicline, medication adherence was
      suboptimal, and greater OOP cost was associated with lower adherence and lower
      odds of refilling varenicline.

PMID- 24856598
TI  - Persistence and compliance with pazopanib in patients with advanced renal cell
      carcinoma within a U.S. administrative claims database.
AB  - BACKGROUND: Pazopanib is an oral tyrosine kinase inhibitor with demonstrated
      efficacy and tolerability in patients with advanced renal cell carcinoma (RCC).
      OBJECTIVE: To examine pazopanib persistence and compliance (adherence) and other
      drug utilization patterns in both treatment-naive (first-line) patients and those
      previously treated with RCC therapy in the real-world setting. Key factors
      affecting persistence and compliance were also explored. METHODS: This was a
      retrospective claims analysis using the Truven Health MarketScan Databases to
      cover claims activity from October 2007 through March 2012. Patients with
      advanced RCC aged >= 18 years who had received pazopanib with 180 days of follow
      up were included. Bivariate comparisons of results from first-line and previously
      treated patients with RCC were conducted. Pazopanib persistence was measured
      using (a) estimated level of persistence with therapy (ELPT; i.e., the percentage
      of patients remaining on therapy at 30, 60, and 90 days [patients were censored
      at 180 days]); (b) time to discontinuation (i.e., duration of therapy); and (c)
      proportion of days covered (PDC; i.e., the ratio of [total days drug available
      minus days' supply of last prescription] to [last prescription date minus first
      prescription date]). Compliance was measured by medication possession ratio (MPR;
      i.e., the ratio of [total days' supply minus days' supply of last prescription]
      to [last prescription date minus first prescription date]). Other drug
      utilization measures included days' supply, time to initiation, time to
      switching, and dose-related measures. Random forest models were used to explore
      key factors of pazopanib persistence and compliance. RESULTS: A total of 143
      patients met all inclusion criteria; 43.3% were treated with pazopanib first line
      (first-line cohort), and 56.6% had >= 1 prior lines of therapy (previously
      treated cohort). The mean (+/- standard deviation [SD]) age of patients was 62.9
      (+/- 10.3) years, and 71.3% of them were males. Continuous pazopanib therapy for
      up to 90 days was observed in greater than 50% of patients in both cohorts. In
      the first-line cohort, ELPT at 30, 60, and 90 days was 98.39%, 70.97%, and
      56.45%, respectively; the mean (+/- SD) number of days to discontinuation was
      112.2 (+/- 62.8); the mean (+/- SD) PDC was 84.7% (+/- 16.7%); and the mean (+/-
      SD) MPR was 85.2% (+/- 16.9%). Similar results were observed in the previously
      treated population: ELPT at 30, 60, and 90 days was 98.77%, 75.31%, and 58.02%,
      respectively; the mean (+/- SD) number of days to discontinuation was 118.7 (+/-
      61.4); the mean (+/- SD) PDC was 87.8% (+/- 13.5%); and the mean (+/- SD) MPR was
      90.1% (+/- 13.9%). Differences between the 2 cohorts were not statistically
      significant. More than 90% of patients in both cohorts had at least a 30-day
      supply of therapy (91.9% of first-line versus 90.2% of previously treated; P =
      0.153). The mean (+/- SD) time from metastatic diagnosis to start of pazopanib
      therapy was 104.7 (+/- 199.3) days in the first-line cohort and 360.9 (+/- 187.0)
      days in previously treated patients (P = 0.001). Forty-six patients switched to
      another therapy: 17 patients in the first-line cohort and 29 patients in the
      previously treated cohort; the mean (+/- SD) time to switching therapy from each
      cohort was 94.7 (+/- 41.4) days and 87.8 (+/- 49.6) days (P = 0.146),
      respectively. Statistically significant differences were observed for the
      starting and ending doses between the 2 cohorts. The average daily dosage of
      pazopanib was greater than 700 mg in both cohorts (P = 0.055), with a maximum
      dose of 800 mg. Random forest models demonstrated that younger age and higher
      comorbidity predicted both higher persistence and compliance. CONCLUSIONS: In
      this observational study, greater than 50% of patients with advanced RCC were on
      pazopanib for almost 4 months, with the majority of both cohorts achieving high
      persistence and high compliance. Additionally, younger age and higher comorbidity
      index were the strongest predictors of both greater persistence and compliance.
      Further studies with larger cohorts and longer follow-up are needed to validate
      these findings.

PMID- 24856599
TI  - Impact of a prior authorization policy for montelukast on clinical outcomes for
      asthma and allergic rhinitis among children and adolescents in a state Medicaid
      program.
AB  - BACKGROUND: Public policymakers often struggle with increased membership and
      limited budgets. Restrictions, commonly in the form of prior authorizations, are
      often placed on more costly pharmaceuticals, especially when lower cost or more
      effective products are available. Restrictions placed on products for difficult
      to-manage disease states must be reviewed in order to ensure that unintended
      clinical consequences do not occur. OBJECTIVE: To assess the impact of a prior
      authorization policy for montelukast on clinical outcomes for asthma and allergic
      rhinitis among children and adolescent members of Oklahoma Medicaid (MOK) from
      2007 through 2010. METHODS: Monthly individual-level utilization data were
      collected from MOK paid pharmacy and medical claims from January 1, 2007, through
      December 31, 2010, for members with asthma and/or allergic rhinitis. Members who
      were continuously eligible for the entire 48-month review period were included.
      The effect of a prior authorization policy for montelukast on emergency room (ER)
      utilization, disease-related physician office visits (DRV), and antibiotic
      prescription utilization (ABX) was analyzed using segmented logistic regression.
      RESULTS: For all 3 outcomes, decreases in mean number of claims per member per
      month were detected when comparing the pre-implementation and post-implementation
      prior authorization periods for all 3 disease states of asthma, allergic
      rhinitis, or both. Odds of having an ER event at the point of prior authorization
      implementation were 0.71 (P  less than  0.001) and were 1.29 (P  less than 
      0.001) and 1.26 (P  less than  0.001) for DRV and ABX, respectively. Overall
      trend in odds was 1.02 (P  less than  0.001), 0.93 (P  less than  0.001), and
      0.95 (P  less than  0.001) for ER, DRV, and ABX, but during the post
      implementation period, the odds were 0.92 (P  less than  0.001) for ER and 1.03
      (P  less than  0.001) for both DRV and ABX. The final result was an increasing
      trend prior to implementation for ER, a decrease at implementation, and a
      continued decrease in odds of an event in the post-implementation period.
      However, for DRV and ABX, there was an overall decrease in trend regardless of
      period, with a small increase in odds at the point of implementation.
      CONCLUSIONS: While there was a point increase at implementation for DRV and ABX,
      the overall trend remained negative, indicating that no unexpected adverse
      clinical outcomes occurred. Additionally, no signal was found in ER use after
      implementation to indicate that unintended consequences occurred, particularly
      for those patients with asthma.

PMID- 24856600
TI  - Current drug therapies for rosacea: a chronic vascular and inflammatory skin
      disease.
AB  - BACKGROUND: Rosacea is a chronic skin disorder that presents with abnormal
      vascular and inflammatory conditions. Clinical manifestations include flushing,
      facial erythema, inflammatory papules and pustules, telangiectasias, edema, and
      watery or irritated eyes. OBJECTIVE: To discuss the evolving pathophysiology of
      rosacea, factors involved in promoting the chronic vascular and inflammatory
      abnormalities seen in rosacea, and the available drug therapies for the
      condition. DISCUSSION: Chronic inflammation and vascular changes are believed to
      be underlying factors in the pathophysiology of rosacea. Aberrant cathelicidin
      expression, elevated kallikrein 5 (KLK5) proteolytic activity, and altered toll
      like receptor 2 (TLR2) expression have been reported in rosacea skin leading to
      the production of proinflammatory cytokines. Until recently, drug therapies only
      targeted the inflammatory lesions (papules and pustules) and transient erythema
      associated with these inflammatory lesions of rosacea. Brimonidine tartrate gel
      0.5% was recently approved for the treatment of persistent (nontransient) facial
      erythema of rosacea, acting primarily on the cutaneous vascular component of the
      disease. CONCLUSION: Rosacea is a chronic vascular and inflammatory skin disease.
      Understanding the role of factors that trigger the onset of rosacea symptoms and
      exacerbate the condition is crucial in treating this skin disease.

PMID- 24856601
TI  - Antidepressant treatment persistence in low-income, insured pregnant women.
AB  - BACKGROUND: Pregnant women with depression face complicated treatment decisions,
      either because of the risk associated with not treating depression or because of
      the risks associated with antidepressant use. Approximately 1 in 5 women
      experience depressive symptoms during pregnancy. This information suggests that
      many women may take an antidepressant at some time during pregnancy. Once
      pregnant women initiate antidepressant prescription pharmacotherapy, medication
      treatment persistence plays an important role in managing depression, yet little
      is known regarding antidepressant use behavior in pregnant women. OBJECTIVE: To
      determine antenatal antidepressant treatment nonpersistence and associated
      factors in low-income, insured pregnant women. METHODS: We identified eligible
      pregnant women (>= 18 years) diagnosed with major depression who initiated
      antidepressant medications during pregnancy from South Carolina Medicaid claims
      data (2004-2009). Our main outcome measure was treatment nonpersistence to
      antidepressant therapy during pregnancy. We defined treatment nonpersistence to
      antidepressant pharmacotherapy as having a gap between 2 consecutive
      prescriptions lasting at least 15 days during pregnancy. We applied a
      proportional hazards model to identify predictors associated with the risk for
      antidepressant nonpersistence during pregnancy. RESULTS: Of 804 pregnant women
      meeting study criteria, nearly 45% of this cohort did not continue to use
      antidepressant pharmacotherapy, showing a gap >= 15 days between 2 prescriptions,
      after initiating antidepressant therapy during pregnancy. Women reporting
      nonwhite race were 36% more likely to show a gap in antidepressant medication use
      during pregnancy than white women. Women with a history of antidepressant use
      before pregnancy were 44% more likely to discontinue the antidepressant therapy
      during pregnancy. CONCLUSIONS: Treatment persistence to antidepressant
      medications was poor during pregnancy in low-income, insured pregnant women.
      Individualized treatment might be considered to reduce the risks of untreated
      depression and antenatal antidepressant use in vulnerable women.

PMID- 24856602
TI  - Exploration of claims-based utilization measures for detecting potential
      nonmedical use of prescription drugs.
AB  - BACKGROUND: Nonmedical use of prescription medication is a significant and
      growing public health concern in the United States. Drug utilization measures
      that can reliably quantify the extent of nonmedical use of a given medication or
      medication class would greatly facilitate efforts to identify, monitor, and
      constrain nonmedical prescription drug use. Measures making use of prescription
      claims data would be especially valuable given the ready availability of these
      data among health care plans and payers. OBJECTIVE: To explore the extent to
      which claims-based utilization measures can provide information that aids in
      identifying and quantifying nonmedical drug use. METHODS: Prescription claims
      from a large employer-based administrative claims database (MarketScan) were used
      to evaluate drug utilization during the first year after an index prescription
      for 6 classes of drugs with a known abuse potential and 3 classes without.
      Traditional population-level measures of adherence (i.e., medication possession
      ratio [MPR] and proportion of days covered [PDC]) and a novel measure of
      overlapping days supply (MPR/PDC ratio) were calculated for all medications.
      Measures of asymmetrical use within a population were evaluated with the Lorenz
      curve, representing the total drug supply used by the heaviest 1%, 5%, and 50% of
      all users. All of the measures across compounds were compared with Spearman
      nonparametric rank correlations, and the Friedman's test was performed to
      determine whether the rankings were consistent in pairwise analysis. The ability
      of each measure to discriminate between abusable and nonabusable compounds was
      evaluated using the c-statistic. RESULTS: The study cohort included 6,291,810
      patients, mean age 52 years, 57.9% female. The mean MPR and mean PDC for drugs
      with known abuse potential were both lower than for drugs without known abuse
      potential. The MPR/PDC ratio (MPR:PDC) ranged from 1.02-1.09. Highest values for
      the Lorenz-1 curve were seen for acetaminophen with codeine, acetaminophen with
      oxycodone, oxycodone, and acetaminophen with hydrocodone. The individual MPR and
      PDC were strongly correlated to each other (r = 0.99; P  less than  0.001 for
      both), moderately correlated with the MPR:PDC (r = 0.62 and 0.57, respectively)
      and moderately inversely correlated with Lorenz 1 (r = -0.83 and -0.86,
      respectively, P  less than  0.001 for both). The MPR:PDC was inversely correlated
      with the Lorenz-1 (r = -0.39; P = 0.02). After rank ordering individual drugs by
      each measure from highest to lowest value, the MPR:PDC resulted in consistent
      distributions with the individual MPR (P = 0.0097) and PDC (P = 0.0018), but not
      the Lorenz-1 (P = 0.0835), nor Lorenz-50 (P = 0.1343). The MPR, PDC, Lorenz-1,
      and Lorenz-50 were able to discriminate between the drugs with known abuse
      potential and those without (c-statistic 0.979 to 1), while the MPR:PDC was not
      (c-statistic 0.592). CONCLUSIONS: When comparing classes of drugs with a known
      abuse potential with classes of drugs not prone to such use, using an array of
      drug utilization measures, significantly different patterns emerge, although the
      ability of these measures to serve as reliable indicators of the extent of
      nonmedical prescribing may be limited. There is a need for valid and reliable
      algorithms to detect the extent of nonmedical use at a population level to help
      target public health interventions aimed at constraining illicit use. Further
      work is warranted on the development of novel measures that make use of
      individual patient-level use patterns.

PMID- 24856610
TI  - [Acquired amusia and musical anhedonia].
AB  - Amusia is defined as an auditory agnosia, specifically related to music,
      resulting from a cerebral lesion or being of congenital origin. Amusia is rarely
      associated to musical anhedonia. We report the case of a 43-year-old patient who
      suffered in January 2012 from a right ischemic lesion affecting the superior
      temporal cortex, in particular lateral Heschl Gyrus and the posterior part of the
      Superior Temporal Gyrus (Brodmann areas 21 and 22). Neuropsychological tests
      revealed an amusia combined to musical anhedonia. The specificity of this case is
      based on the combination of both syndromes highlighting the relation between
      neural networks involved in the processing of musical information in both its
      perceptual and emotional components.

PMID- 24856613
TI  - Electronic structure and optical properties of the intrinsically chiral 16
      electron superatom complex [Au20(PP3)4](4+).
AB  - The recently solved crystal structure of the [Au20(PP3)4]Cl4 cluster (PP3: tris(2
      (diphenylphophino)ethyl)phosphine) is examined using density functional theory
      (DFT). The Au20 core of the cluster is intrinsically chiral by the arrangement of
      the Au atoms. This is in contrast to the chirality of thiolate-protected gold
      clusters, in which the protecting Au-thiolate units are arranged in chiral
      patterns on achiral cores. We interpret the electronic structure of the
      [Au20(PP3)4]Cl4 cluster in terms of the superatom complex model. The 16-electron
      cluster cannot be interpreted as a dimer of 8-electron clusters (which are
      magic). Instead, a superatomic electron configuration of 1S(2) 1P(6) 1D(6) 2S(2)
      is found. The 2S band is strongly stabilized, and the 1D states are nondegenerate
      with a large gap. Ligand protection of the (Au20)(4+) core leads to a significant
      increase of the HL-gap and thus stabilization. We also tested a charge of +II,
      which would give rise to an 18-electron superatom complex. Our results indicate
      that the 16-electron cluster is indeed more stable. We also investigate the
      optical properties of the cluster. The experimental absorption spectrum is well
      reproduced by time-dependent DFT. Prominent transitions are analyzed by time
      dependent density-functional perturbation theory. The intrinsic chirality of the
      cluster is compared to that of Au38(SR)24. We observe that the chiral arrangement
      of the protecting Au-SR units in Au38(SR)24 has very strong influence on the
      strength of the CD spectra, whereas phosphine protection in the title compound
      does not. 

PMID- 24856611
TI  - New hepatitis E virus genotype in camels, the Middle East.
AB  - In a molecular epidemiology study of hepatitis E virus (HEV) in dromedaries in
      Dubai, United Arab Emirates, HEV was detected in fecal samples from 3 camels.
      Complete genome sequencing of 2 strains showed >20% overall nucleotide difference
      to known HEVs. Comparative genomic and phylogenetic analyses revealed a
      previously unrecognized HEV genotype. 

PMID- 24856612
TI  - Reduced risk of hypoglycemia with once-daily glargine versus twice-daily NPH and
      number needed to harm with NPH to demonstrate the risk of one additional
      hypoglycemic event in type 2 diabetes: Evidence from a long-term controlled
      trial.
AB  - AIMS: This analysis evaluated HbA1c-adjusted hypoglycemia risk with glargine
      versus neutral protamine Hagedorn (NPH) over a 5-year study in patients with Type
      2 diabetes mellitus (T2DM). Clinical significance was assessed using number
      needed to harm (NNH) to demonstrate the risk of one additional patient
      experiencing at least one hypoglycemic event. METHODS: Individual patient-level
      data for symptomatic documented hypoglycemia and HbA1c values from a 5-year
      randomized study comparing once-daily glargine (n=513) with twice-daily NPH
      (n=504) were analyzed. Symptomatic hypoglycemia was categorized according to
      concurrent self-monitoring blood glucose levels and need for assistance.
      Hypoglycemic events per patient-year as a function of HbA1c were fitted by
      negative binomial regression using treatment and HbA1c at endpoint as independent
      variables. An estimate of NNH was derived from logistic regression models.
      RESULTS: The cumulative number of symptomatic hypoglycemia events was
      consistently lower with glargine compared with NPH over 5years. Compared with
      twice-daily NPH, once-daily glargine treatment resulted in significantly lower
      adjusted odds ratios (OR) for all daytime hypoglycemia (OR 0.74; p=0.030) and any
      severe event (OR 0.64; p=0.035), representing a 26% and 36% reduction in the odds
      of daytime and severe hypoglycemia, respectively. Our model predicts that, if 25
      patients were treated with NPH instead of glargine, then one additional patient
      would experience at least one severe hypoglycemic event. CONCLUSIONS: This
      analysis of long-term insulin treatment confirms findings from short-term studies
      and demonstrates that glargine provides sustained, clinically meaningful
      reductions in risk of hypoglycemia compared with NPH in patients with T2DM.

PMID- 24856614
TI  - Synthesis and pharmacological evaluation of analogues of benzyl quinolone
      carboxylic acid (BQCA) designed to bind irreversibly to an allosteric site of the
      M 1 muscarinic acetylcholine receptor.
AB  - Activation of the M1 muscarinic acetylcholine receptor (mAChR) is a prospective
      treatment for alleviating cognitive decline experienced in central nervous system
      (CNS) disorders. Current therapeutics indiscriminately enhance the activity of
      the endogenous neurotransmitter ACh, leading to side effects. BQCA is a positive
      allosteric modulator and allosteric agonist at the M1 mAChR that has high subtype
      selectivity and is a promising template from which to generate higher affinity,
      more pharmacokinetically viable drug candidates. However, to efficiently guide
      rational drug design, the binding site of BQCA needs to be conclusively
      elucidated. We report the synthesis and pharmacological validation of BQCA
      analogues designed to bind irreversibly to the M1 mAChR. One analogue in
      particular, 11, can serve as a useful structural probe to confirm the location of
      the BQCA binding site; ideally, by co-crystallization with the M1 mAChR.
      Furthermore, this ligand may also be used as a pharmacological tool with a range
      of applications. 

PMID- 24856615
TI  - Missing patients in a regional trauma registry: incidence and predictors.
AB  - BACKGROUND: Trauma systems have data registries in order to describe and evaluate
      (the quality of) trauma care. If results between centres and countries
      (benchmarking) are to be compared, data has to be accurate, reliable and
      complete. All trauma registries deal with incompleteness. A contributor to
      incompleteness of the data is failure to include patients that fulfil the
      criteria; the so-called missing patients. The aim of this study is to assess the
      number of missing patients in our regional trauma registry and to identify
      predictors for being missing from the trauma registry. METHODS: A random sample
      was taken. Four calendar weeks from 2012 were selected and medical files of all
      consecutive presentations to the emergency department or trauma room during those
      weeks were studied. Patients who were already correctly included in the trauma
      registry were assigned to the 'included' group and patients who should have been
      but were not to the 'missing' group. Multivariable logistic regression analysis
      was performed to identify predictors for being missed from the trauma registry.
      RESULTS: Of a total of 338 patients, 50 (15%) were identified as missing.
      Characteristics of the missing patients did not differ substantially from the
      included patients. Transfer to another hospital after initial assessment and
      presentation in a Level 3 hospital compared to a Level 1 hospital were
      independent predictors for being missed from the trauma registry, with an
      adjusted odds ratio of 5.86 (95% CI: 2.08-16.52) and 6.64 (95% CI: 1.86-23.78),
      respectively. CONCLUSIONS: Overall, 15% of the patients who met the inclusion
      criteria of the trauma registry were not included in the registry. Special
      attention should be paid to patients who are transferred to other hospitals in
      the network after initial assessment and to registration in Level 3 hospitals.

PMID- 24856616
TI  - Understanding discordant meta-analyses of convective dialytic therapies for
      chronic kidney failure.

PMID- 24856617
TI  - In reply to 'rituximab and B-cell return in ANCA-associated vasculitis'.

PMID- 24856619
TI  - Etiological versus prognostic models in cohort studies.

PMID- 24856618
TI  - Rituximab and B-cell return in ANCA-associated vasculitis.

PMID- 24856620
TI  - Nutritional supplement use in hemodialysis patients.

PMID- 24856621
TI  - In reply to 'etiological versus prognostic models in cohort studies' and
      'nutritional supplement use in hemodialysis patients'.

PMID- 24856622
TI  - Quiz page June 2014: a 45-year-old woman with acute anuria.

PMID- 24856624
TI  - Management of central nervous system tumours in children.
AB  - This article reviews current approaches to management of central nervous system
      tumours of childhood, highlighting aspects particularly pertinent to the
      paediatric population.

PMID- 24856623
TI  - Legal factors associated with change in alcohol use and partner violence among
      offenders.
AB  - Intimate partner violence (IPV) is a pervasive social concern that may be
      exacerbated by high rates of alcohol dependence among perpetrators. Society has
      attempted to combat IPV through various legal interventions, but the effects of
      specific legal factors on behavioral change and treatment compliance remain
      largely unexamined. The primary focus of the current study was to comprehensively
      evaluate the impact of various legal factors (i.e., judicial mandate, judicial
      monitoring, stage of change, and stake in conformity) on mandatory treatment
      compliance and behavioral change over a 12 week post-adjudication period among a
      high-risk sample of alcohol dependent IPV offenders (N = 60). Growth curve
      analyses revealed effects of judicial monitoring and stage of change such that
      participants reporting low perceived judicial monitoring and early stages of
      change reported higher initial levels and a more rapid reduction in IPV than
      those reporting high perceived judicial monitoring and late stages of change, who
      reported consistently low IPV. Although we found that legal factors were poor
      predictors of treatment compliance and alcohol use during treatment, the
      association between alcohol and IPV was moderated by the legal factors. Stake in
      conformity was negatively associated with IPV among low alcohol users and
      positively associated among high alcohol users whereas stage of change was
      negatively associated with IPV among high alcohol users. The current results
      suggest that pretreatment legal factors may represent an important consideration
      in reducing IPV among alcohol dependent offenders. Further research is required
      to determine the efficacy of legal factors in isolation of treatment as well as
      methods of manipulating these factors to optimally compliment a prescribed course
      of treatment.

PMID- 24856626
TI  - Post-mortem beta-hydroxybutyrate determination in synovial fluid.
AB  - beta-hydroxybutyrate concentrations were determined in blood and synovial fluid
      in a series of medico-legal cases including hypothermia fatalities, individuals
      found dead in a cold environment and non-hypothermia cases with various, non
      traumatic causes of death. Hypothermia was considered to be the cause of death
      according to circumstantial elements indicating exposure to cold, autopsy
      findings, biochemical investigation results and exclusion of other causes of
      death. The intention of this study was to characterize beta-hydroxybutyrate
      distribution in synovial fluid and assess its usefulness for the postmortem
      diagnosis of antemortem abnormalities in blood beta-hydroxybutyrate levels.
      Unenhanced CT scans, autopsies, histology, neuropathology, toxicology, and
      biochemistry were systematically performed. Within the limited number of subjects
      included in the study, the results indicate that abnormalities in antemortem beta
      hydroxybutyrate blood levels, as may be observed in hypothermia fatalities, are
      reflected in postmortem synovial fluid values. These preliminary findings
      notwithstanding, synovial fluid analysis to determine beta-hydroxybutyrate is
      unlikely to be generally applied due to the more invasive collection technique it
      requires and could be limited to special cases in which biological fluids
      systematically collected upon autopsy are unavailable. 

PMID- 24856625
TI  - Distinguishing and quantification of the human visual pathways using high-spatial
      resolution diffusion tensor tractography.
AB  - Quantification of the living human visual system using MRI methods has been
      challenging, but several applications demand a reliable and time-efficient data
      acquisition protocol. In this study, we demonstrate the utility of high-spatial
      resolution diffusion tensor fiber tractography (DTT) in reconstructing and
      quantifying the human visual pathways. Five healthy males, age range 24-37years,
      were studied after approval of the institutional review board (IRB) at The
      University of Texas Health Science Center at Houston. We acquired diffusion
      tensor imaging (DTI) data with 1-mm slice thickness on a 3.0-Tesla clinical MRI
      scanner and analyzed the data using DTT with the fiber assignment by continuous
      tractography (FACT) algorithm. By utilizing the high-spatial-resolution DTI
      protocol with FACT algorithm, we were able to reconstruct and quantify bilateral
      optic pathways including the optic chiasm, optic tract, optic radiations free of
      contamination from neighboring white matter tracts. 

PMID- 24856627
TI  - Oral fluid testing for pertussis, England and wales, june 2007-august 2009.
AB  - Existing pertussis surveillance systems tend to underidentify less severe cases
      among older children and adults. For routine follow-up of notified, nonconfirmed,
      clinically diagnosed pertussis cases, use of an oral fluid test was pilot tested
      in England and Wales during June 2007-August 2009. During that period, 1,852
      cases of pertussis were confirmed by established laboratory methods and another
      591 by oral fluid testing only. Although introduction of serologic testing in
      2002 led to the greatest increase in ascertainment of pertussis, oral fluid
      testing increased laboratory ascertainment by 32% overall; maximal increase
      (124%) occurred among children 5-9 years of age. Patients whose pertussis was
      confirmed by oral fluid testing were least likely to be hospitalized, suggesting
      that milder community cases were being confirmed by this method. Oral fluid
      testing is an easily administered, noninvasive surveillance tool that could
      further our understanding of pertussis epidemiology and thereby contribute to
      decisions on vaccination strategies. 

PMID- 24856628
TI  - Radiographic assessment of prosthetic humeral head size after anatomic shoulder
      arthroplasty.
AB  - BACKGROUND: Restoring the premorbid proximal humeral anatomy during shoulder
      arthroplasty is critical yet can be difficult because of the deformity of the
      arthritic head. The purpose of this study was to measure the variation between
      surgeons and between types of prosthetics in reproducing the anatomic center of
      rotation (COR) of the humeral head after anatomic shoulder arthroplasty. METHODS:
      The anteroposterior radiographs of 125 stemmed and 43 resurfacing shoulder
      arthroplasties, performed by 5 experienced surgeons, were analyzed. All patients
      had primary replacement for treatment of end-stage glenohumeral arthritis. A best
      fit circle to preserved nonarticular humeral landmarks was used to define the
      difference between the anatomic COR and the prosthetic COR. A difference in COR
      of >3.0 mm was considered clinically significant and analyzed for the cause of
      this deviation. RESULTS: The average deviation of the postoperative COR from the
      anatomic COR was 2.5 +/- 1.6 mm for stemmed cases and 3.8 +/- 2.1 mm for
      resurfacings. Thirty-nine stemmed cases (31.2%) and 28 resurfacings (65.1%) were
      beyond 3.0 mm of deviation and regarded as outliers. The majority of the stemmed
      outliers and all resurfacing outliers were overstuffed. An improper humeral head
      size selection and inadequate reaming were the main reasons for the deviation in
      stemmed and resurfacing outliers, respectively. CONCLUSION: A large percentage of
      shoulder replacements demonstrated significant deviations from an anatomic
      reconstruction. Resurfacing arthroplasty exhibited significantly greater
      deviations compared with stemmed arthroplasty (P < .001), indicating that
      surgeons have more difficulty in restoring the anatomy with resurfacings. Further
      studies are needed to assess the clinical impact of these deviations.

PMID- 24856635
TI  - Synthetic control of isolated, single functional groups on silica surfaces.
AB  - We report control of the density of isolated, single functional groups in
      homogeneously mixed trichloroalkyl silanes on various silica surfaces. The
      functional groups are covalently bound to a silane derived from the Rink resin.
      This Rink-silane is reactive to any nucleophile. Control over the density of
      functional groups is achieved by diluting the immersion solution containing the
      Rink-silane with an inert silane, octadecyltrichlorsilane. The isolated nature of
      the functional groups is confirmed by the stochastic blinking of fluorescent
      single boron-dipyrromethane dyes imaged in total internal reflection geometry.
      The robust character of silane monolayers allows facile covalent binding and
      cleavage of molecular species from silica surfaces as well as general synthetic
      transformations to be conducted. This is shown by the covalent attachment and
      then cleavage of a naphthalene chromophore. This low-cost and scalable platform
      has great potential for use in sensing, molecular electronics, semiconductor
      processing, and the investigation of fundamental processes in catalysis and the
      kinetics of molecular association. 

PMID- 24856634
TI  - How to learn about teaching: An evolutionary framework for the study of teaching
      behavior in humans and other animals.
AB  - The human species is more reliant on cultural adaptation than any other species,
      but it is unclear how observational learning can give rise to the faithful
      transmission of cultural adaptations. One possibility is that teaching
      facilitates accurate social transmission by narrowing the range of inferences
      that learners make. However, there is wide disagreement about how to define
      teaching, and how to interpret the empirical evidence for teaching across
      cultures and species. In this article I argue that disputes about the nature and
      prevalence of teaching across human societies and nonhuman animals are based on a
      number of deep-rooted theoretical differences between fields, as well as on
      important differences in how teaching is defined. To reconcile these disparate
      bodies of research, I review the three major approaches to the study of teaching 
      mentalistic, culture-based, and functionalist - and outline the research
      questions about teaching that each addresses. I then argue for a new, integrated
      framework that differentiates between teaching types according to the specific
      adaptive problems that each type solves, and apply this framework to restructure
      current empirical evidence on teaching in humans and nonhuman animals. This
      integrative framework generates novel insights, with broad implications for the
      study of the evolution of teaching, including the roles of cognitive constraints
      and cooperative dilemmas in how and when teaching evolves. Finally, I propose an
      explanation for why some types of teaching are uniquely human, and discuss new
      directions for research motivated by this framework.

PMID- 24856636
TI  - Goal setting with caregivers of adults in the community: a mixed methods
      systematic review.
AB  - PURPOSE: To examine how goal setting is used with caregivers of community
      residing adults and the effect of goal setting practices in improving the
      outcomes. METHODS: A mixed methods systematic review was conducted. The
      methodological rigour of included studies was critiqued using Cochrane
      Collaboration's risk of bias assessment tool, Downs and Black checklist and a
      framework for evaluating qualitative research. Narrative synthesis was created
      through tabulation and categorisation, visual mapping of the goal setting
      process, thematic analysis on common goal setting features and critical
      reflection on the accuracy and robustness of the synthesis. RESULTS: Seventeen
      studies were included: 10 randomised trials, 5 other quantitative studies and two
      descriptive studies which incorporated qualitative methods. The trials
      demonstrated a relatively low risk of bias in contrast to the other studies that
      had varied methodological rigour. No studies isolated the effect of the goal
      setting process on outcomes and therefore the effectiveness of goal setting could
      not be evaluated. However, through a narrative synthesis six prominent features
      of collaborative goal setting were identified. CONCLUSIONS: Despite the fact that
      goal setting is an important component of client-centred care, and the prominence
      of client-centred care in healthcare discourse, the review uncovered a
      surprisingly limited number of studies. Goal setting is an elusive process that
      is of therapeutic value and warrants further investigation. Implications for
      Rehabilitation The current body of empirical evidence suggests that there are six
      prominent features of collaborative goal setting with caregivers. The goals that
      are most important to caregivers are often different to those that are important
      to clinicians; it is important that caregivers and clinicians agree on goals to
      maximise adherence to treatment and goal attainment. The quality of evidence for
      goal setting with caregivers is limited although some intervention trials
      illustrate the usefulness of collaborative goal setting in contributing to
      improved outcomes.

PMID- 24856637
TI  - Chronic pain affects the whole person--a phenomenological study.
AB  - PURPOSE: The aim of this qualitative study was to explore participants'
      perspectives on the effects of chronic pain on the psychophysical unity. METHODS:
      Thirty-four chronic pain outpatients were interviewed, and the transcribed
      interviews were analysed with Giorgi's four-phase phenomenological method. The
      mean age of the participants was 48 years, and 19 of them were women. For 21 of
      the participants, the pain duration was more than 5 years, and most had
      degenerative spinal pain. RESULTS: The results of this whole research project
      indicated that the phenomenon chronic pain consisted of four essential themes:
      Pain affects the whole person, invisibility, negativity, and dominance of pain.
      This study concentrates only on one theme "Chronic pain affects the whole
      person", in which were found eight subthemes in the interviews. The strongest
      argument made by the participants was not the physical pain itself but the
      psychosocial consequences, such as distress, loneliness, lost identity, and low
      quality of life which were their main problems. CONCLUSIONS: In multidisciplinary
      holistic rehabilitation, it is essential to take care of the patient's
      psychological distress. A potential source of psychosocial symptoms may be the
      subjective responses to experience of chronic pain due to the subjective meanings
      of pain. Implications for Rehabilitation About chronic pain Pain is an
      experience, not only an aversive sensation. Intensity of pain describes only the
      sensation, not the experience of pain. In chronic pain, the main complaint may be
      not the physical pain, but the distress. In rehabilitation, the patient needs to
      be taken as a whole person. Multidisciplinary rehabilitation, including patient
      counselling should be the fundamental part of treatment. In rehabilitation, the
      individual meaning of chronic pain needs to be disclosed.

PMID- 24856640
TI  - Exposure of unsuspecting workers to deadly atmospheres in below-ground confined
      spaces and investigation of related whole-air sample composition using adsorption
      gas chromatography.
AB  - Hazardous atmospheres in confined spaces may be obvious when a source of air
      contamination or oxygen (O2) deficiency is recognized. Such is often the case in
      general industry settings, especially with work processes which create hazardous
      atmospheres that may be anticipated. Hazards present in active sewers are also
      well recognized; but the possibility that O2 deficiency or high airborne
      contaminant concentrations may exist in new construction sewers or storm drains
      has been repeatedly ignored with deadly results. Low O2 and high carbon dioxide
      (CO2) concentrations may exist in new construction manholes that have not yet
      been connected to an active sewer or drain system, and these concentrations have
      been shown to vary over time. A recent incident is described where workers
      repeatedly entered such a confined space without incident, but subsequent entry
      resulted in a fatality and a near-miss for a co-worker rescuer. Additional cases
      are discussed, with an emphasis placed on elevated CO2 concentrations as a
      causative factor. A description is provided for the adsorptive gas chromatography
      whole-air analysis methodology used to quantitatively determine atmospheric
      conditions present at this type of fatality site or others after an incident, and
      for the gas chromatography-mass spectrometry method used to provide confirmation
      of analyte identity with high certainty. Many types of confined spaces may be
      encountered in addition to the underground varieties discussed, and many possible
      atmospheric hazards are possible. The definitive whole-air analysis approach
      described here may be of use and should be considered to investigate many
      confined space fatality and near-miss cases, and to better understand the causes
      of dangerous atmosphere conditions that may arise in confined spaces. 

PMID- 24856641
TI  - Quality standards in a rheumatology Day-Care Hospital Unit. The proposal of the
      Spanish Society of Rheumatology Day Hospitals' Working Group.
AB  - BACKGROUND: In recent years, the Rheumatology Day-Care Hospital Units (DHU have
      undergone extensive development. However, the quality standards are poorly
      documented and mainly limited to structure items rather than including broad and
      specific areas of this specialty. OBJECTIVE: To develop specific quality
      standards for Rheumatology DHU. METHODS: After a systematic review of the
      literature and related documents, a working group (WG) involving 8 DHU
      experienced rheumatologists developed an initial proposal of the quality
      standards, under the supervision of an expert methodologist. A second round was
      held by the WG group to review the initial proposal and to consider further
      suggestions. Once the content was agreed upon by consensus, a final report was
      prepared. RESULTS: 17 structure standards, 25 process standards and 10 results
      standards were defined, with special emphasis on specific aspects of the
      Rheumatology DHU. The proposal includes: 1) essential standards to 2) excellent
      standards, 3) a Rheumatology DHU services portfolio and 4) performance criteria.
      CONCLUSIONS: The proposed quality standards are the basis for developing the
      indicators and other management tools for Rheumatology DHU, thereby ensuring a
      patient-oriented practice based on both the evidence and the experience.

PMID- 24856643
TI  - Impact of point-of-care testing for CYP2C19 on platelet inhibition in patients
      with acute coronary syndrome and early dual antiplatelet therapy in the emergency
      setting.
AB  - AIMS: Only limited data exist about the role of point of care CYP2C19 testing in
      the acute setting in the early phase of acute coronary syndromes (ACS).
      Therefore, the present study was designed to investigate the impact of CYP2C19
      loss-of-function point-of-care (POC) genotyping in patients presenting with acute
      coronary syndromes (ACS) and treated with dual antiplatelet therapy in the
      emergency setting. METHODS AND RESULTS: 137 subjects with ACS scheduled for
      percutaneous coronary intervention were consecutively enrolled. Pre- and on
      treatment platelet aggregation was assessed by multiple electrode aggregometry
      (MEA) after stimulation with adenosine diphosphate (ADP). Patients were loaded
      according to current guideline adherent indications and contraindications for use
      of P2Y12 inhibitors in ACS. POC genotyping for CYP2C19*2 was performed in the
      emergency room after obtaining a buccal swab using the Spartan RX CYP2C19 system
      and obtaining patient's informed consent. Prasugrel and ticagrelor treated
      patients had significantly lower PR compared to clopidogrel-treated patients. The
      benefits of prasugrel and ticagrelor compared to clopidogrel treated patients in
      terms of platelet inhibition were more pronounced in CYP2C19*2 carriers. Non
      carriers showed similar inhibition regardless of particular P2Y12 inhibitor
      treatment. Statistical analyses adjusting for factors associated with response
      (e.g. smoking) revealed that CYP2C19*2 allele carrier status and loading with
      different type of P2Y12 receptor blockers were significant predictors of on
      treatment platelet reactivity in the early phase of ACS. CONCLUSION: The results
      of this pilot study of treatment of patients in the early phase of ACS indicate
      that CYP2C19*2 POC genotyping might help to identify patients at risk with poor
      response to clopidogrel treatment, thereby benefiting from reloading and
      switching to alternative P2Y12 receptor inhibition.

PMID- 24856644
TI  - Effects of peroxisome proliferator-activated receptor gamma in simvastatin
      antiplatelet activity: influences on cAMP and mitogen-activated protein kinases.
AB  - Statins are widely used as hypolipidemic drugs, and have beneficial effects in
      reducing cardiovascular events. In addition, recent studies on the pleiotropic
      effects of statins (i.e., simvastatin) reveal that these drugs have many
      additional anti-atherogenic effects, including antiplatelet activity. The
      mechanisms may be partly related to activation of peroxisome proliferator
      activated receptors (PPARs), which are present in human platelets, and whose
      activation inhibits platelet aggregation. However, the details of the signaling
      pathway by which simvastatin inhibits platelet activation via PPARs have not yet
      been completely established. The aim of this study was to examine the mechanisms
      by which the PPAR-mediated pathways contribute to the antiplatelet activity of
      simvastatin. Simvastatin (3-50 MUM) induced PPARalpha and PPARgamma activation in
      a dose-dependent manner in washed platelets. Additionally, simvastatin inhibited
      collagen-induced platelet aggregation, expression of CD62 and PAC-1, and Ca(2+)
      mobilization. These effects of simvastatin on platelet responses were strongly
      reduced by adding a selective PPARgamma antagonist (GW9662), but not PPARalpha
      antagonist (GW6471). Moreover, in the presence of GW9662, simvastatin-mediated
      increase of cyclic adenosine monophosphate (cAMP) production, vasodilator
      stimulated phosphoprotein (VASP) Ser(157) phosphorylation and inhibition of Akt
      phosphorylation were markedly reversed. Furthermore, simvastatin was found to
      inhibit phosphorylation of mitogen-activated protein kinases (MAPKs, i.e., p38
      MAPK, ERK) by increasing the association between PPARgamma and the components of
      MAPKs after platelet activation. Taken together, the present results confirm that
      simvastatin inhibition of platelet activation is mediated by PPARgamma-dependent
      processes, which involves mediating MAPKs signaling, increase of cAMP formation
      and VASP Ser(157) phosphorylation, inhibition of Akt phosphorylation and
      intracellular Ca(2+) mobilization.

PMID- 24856645
TI  - Physical working capacity at fatigue threshold (PWCFT) is associated with
      sarcopenia-related body composition and measures of functionality in older
      adults.
AB  - The relationship between PWCFT and common measures used to assess sarcopenia in
      older adults were examined. Fifty-eight older adults [age: 71.1 +/- 6.2 years;
      body mass index (BMI): 28.0 +/- 5.4 kg/m(2)] completed the testing procedures.
      Sarcopenia-related body composition was measured by dual-energy X-ray
      absorptiometry and participants performed a discontinuous cycle ergometry test to
      determine PWCFT. Functionality assessments included maximal isometric grip
      strength (GRIP) and sit-to-stand (STS) repetitions in 30s. Muscle quality (MQ)
      was defined as GRIP relative to appendicular lean soft tissue (ALM), while
      skeletal muscle index (SMI) was defined as ALM/height(2). Pearson correlations
      were used to examine the relationships among dependent variables. PWCFT showed
      significant relationships with ALM (r=0.57), SMI (r=0.47), body fat percentage
      (BF%) (r=-0.50), GRIP (r=0.49), and STS (r=0.44). For follow-up analyses, study
      participants were categorized into low sarcopenia risk (n=31) or high sarcopenia
      risk (n=27) groups by SMI. Sarcopenia risk was associated with PWCFT [odds ratio
      (OR): 1.051, 95% confidence interval (CI): 1.016-1.087] and STS (OR: 1.305, CI:
      1.060-1.607), but not GRIP (OR: 1.098, CI: 0.989-1.218). Using receiver-operator
      characteristic curve analysis, both PWCFT [area under the curve (AUC): 0.737, CI:
      0.608-0.866, optimal cutoff: 37.5 W] and STS (AUC: 0.749, CI: 0.623-0.874,
      optimal cutoff: 12.5 repetitions) showed discriminative ability with regard to
      sarcopenia risk. The current data suggest that the neuromuscular fatigue
      threshold, as measured by PWCFT, is related to measures of body composition and
      function in older adults.

PMID- 24856646
TI  - Physical exercise and vascular endothelial growth factor (VEGF) in elderly: A
      systematic review.
AB  - The aim of this study was to conduct a systematic review of studies that verified
      the effects of physical exercise on vascular endothelial growth factor (VEGF) in
      elderly. METHODOLOGY: The bibliographic search was conducted in five database,
      from 1990 to 2013, with the following keywords and boolean operators: physical
      exercise OR physical exercise OR physical therapy OR exercise OR training AND
      VEGF OR vascular endothelial growth factor AND aged OR older OR elderly. The
      inclusion criteria were: (1) sample including elderly with average age of 60; (2)
      studies that verified the effects of acute exercise; (3) studies that verified
      the effects of chronic physical exercise; (4) studies with humans; (5) randomized
      controlled trials, randomized non-controlled trials, non-randomized controlled
      trials, non-randomized and non-controlled trials; (6) assessment of VEGF
      peripheral concentrations. RESULTS: Ten studies were selected, and that four of
      them verified an increase of VEGF concentrations after practicing physical
      exercise and six studies did not verify any change on VEGF concentrations.
      CONCLUSION: Different populations found in this study and the different exercise
      protocols applied in the studies of this review make it difficult to establish
      parameters of what would be the best type of exercise to promote an increase on
      the concentrations of VEGF in the elderly. Therefore, we suggest that further
      studies can be performed, so that we can establish some recommendations for this
      population.

PMID- 24856647
TI  - Unilateral otitis media with effusion caused by retained surgical gauze as an
      unintended iatrogenic complication of orthognathic surgery: case report.
AB  - Inadvertent retention of surgical gauze during an operation can have disastrous
      consequences for both the patient and the surgeon. Several cases have been
      reported, particularly after abdominal surgery. However, it has never to our
      knowledge been reported as a leading cause of dysfunction of the Eustachian tube
      after orthognathic surgery. We recently encountered a patient in whom it
      presented with unilateral otitis media with an effusion after orthognathic
      surgery. All surgeons involved with orthognathic surgery should be aware that
      remnants of surgical gauze after orthognathic surgery can compromise the
      Eustachian tube and cause otitis media with an effusion. 

PMID- 24856648
TI  - Impact of obstructive sleep apnea on the 24-h metabolic hormone profile.
AB  - OBJECTIVE: Obstructive sleep apnea (OSA) has been associated with metabolic
      disorders. Sleep-disordered breathing could generate an altered rhythm in the
      expression of metabolic hormones, which could predispose to metabolic disorders.
      The aim of this study was to evaluate the effect of sleep apnea on diurnal
      variations in metabolic hormones. METHODS: Thirty-seven male, newly diagnosed,
      patients with OSA with an apnea-hypopnea index (AHI) > or = 20/h and 11 male
      controls (AHI <10/h) matched for body mass index (+/-3 kg/m2) were included. Six
      different samples were obtained from each subject during a period of 24h. Levels
      of the metabolic hormones ghrelin, leptin, resistin, and adiponectin were
      measured in plasma by immunoassay. RESULTS: Patients with OSA (AHI (mean+/-SD)
      46+/-26/h) were older than the controls (42+/-9 vs. 33+/-9 years, P=0.01).
      Differences in metabolic hormones between groups did not reach statistical
      significance at any point in the evaluation. No significant differences were
      observed in the area under the curve for any of the hormones analysed. Likewise,
      we did not detect diurnal variations in metabolic hormones. CONCLUSIONS: The
      results of this study indicate that the day-night variations in the levels of
      several metabolic hormones are not influenced by the presence of sleep apnea.

PMID- 24856650
TI  - Mechanisms of selenomethionine developmental toxicity and the impacts of combined
      hypersaline conditions on Japanese medaka (Oryzias latipes).
AB  - Selenium (Se) is an essential micronutrient that can cause embryotoxicty at
      levels 7-30 times above essential concentrations. Exposure to hypersaline
      conditions and 50 MUM selenomethionine (SeMet) decreased embryo hatch and
      depleted glutathione in Japanese medaka embryos without affecting Se
      accumulation. To better understand the impacts of nonchemical stressors on
      developmental toxicity of Se in fish, several adverse outcome pathways were
      evaluated in the Japanese medaka (Oryzias latipes). We treated medaka embryos at
      12 h post fertilization with 50 MUM SeMet for 12 hours in freshwater or in 13
      ppth hypersalinity and evaluated the contributions of oxidative stress, the
      unfolded protein response and apoptosis to reduced hatch. Exposure to SeMet and
      hypersalinity decreased embryo hatch to 3.7% +/- 1.95, and induced teratogenesis
      in 100% +/- 0 of hatched embryos. In contrast, treatments of freshwater,
      saltwater, and SeMet in freshwater resulted in 89.8% +/- 3.91-86.7% +/- 3.87
      hatch, and no significant increase in deformities. We found no significant
      differences in lipid peroxidation, indicating that oxidative stress may not be
      responsible for the observed toxicity in embryos at this time point (24 h).
      Although significant changes in apoptosis were not observed, we witnessed up to
      100 fold increases in transcripts of the endoplasmic reticulum (ER) chaperone,
      immunoglobulin binding protein (BiP) and trends toward increasing downstream
      signals, activating transcription factor 4 (ATF4) and ATF6 indicating potential
      contributions of the unfolded protein response to the effects of SeMet and
      hypersaline conditions. These data indicate that multiple adverse outcome
      pathways may be responsible for the developmental toxicity of Se and salinity,
      and these pathways may be time dependent. 

PMID- 24856652
TI  - A survey of breast imaging fellowship programs: current status of curriculum and
      training in the United States and Canada.
AB  - PURPOSE: The Society of Breast Imaging and the Education Committee of the ACR
      Breast Commission conducted a survey of breast imaging fellowship programs to
      determine the status of fellowship curricula, help identify strengths and
      potential areas for improvement, and assess the current demand for fellowship
      programs. METHODS: In 2012, a two-part survey was emailed to breast imaging
      fellowship directors from 72 fellowship programs. RESULTS: Of the 66 respondents,
      a total of 115 positions were identified. There were 90 positions with 9-12
      months of breast imaging, and 25 positions with 6 months focused on breast
      imaging. Approximately two-thirds of programs reported an increase in the number
      of fellowship applicants, with three-quarters having 3 or more applicants for
      each position. All programs offered digital mammography, breast MRI, and
      diagnostic ultrasound services, and nearly all provided experience with
      interventional procedures. Approximately one-third provided breast screening
      ultrasound training. More than two-thirds required at least a 1-day rotation with
      a breast surgeon. Important nonclinical areas of training were not addressed in
      many programs. Approximately 40% of programs did not offer training related to
      the practice audit, and one-third of programs did not provide formal training
      related to quality control. CONCLUSIONS: Breast imaging fellowships are currently
      in higher demand than in the past. Most fellowship programs provide training in
      the key imaging modalities and interventional procedures. Potential gaps in
      training for many programs include the practice audit, quality control
      procedures, breast positioning, and mammography technical factors.

PMID- 24856651
TI  - Oncologic results, functional outcomes, and complication rates of transperitoneal
      robotic assisted radical prostatectomy: single centre's experience.
AB  - BACKGROUND: We report the operative details and short term oncologic and
      functional outcome of the first 334 Robotic-assisted radical prostatectomy
      experiences for organ confined prostate cancer METHODS: From August 2009 to
      December 2012, details of 334 consecutive patients were retrospectively analyzed.
      The analyzed parameters included: preoperative, per-operative characteristics,
      postoperative minor and major complications, positive surgical margin continence,
      potency, and biochemical progression at the follow-up period. RESULTS: The
      classical extrafascial, interfascial, intrafascial and fascia sparing radical
      prostatectomy were performed in 31, 41, 200, and 62 cases, respectively. The mean
      operation time was 213.8+/-90.1minutes, and the mean estimated blood loss was
      116.1+/-58.9cc during operation. A nerve-sparing procedure was performed
      bilaterally in 198 (59.3%) cases and unilaterally in 126 (37.7%) cases. The
      catheter was removed on postoperative day 9, 1+/-1.9. Surgical margin was
      positive in 36 (10.7%) patients. The overall, pT2, pT3a and pT3b PSM rates were 8
      (2.4%), 12 (3.6%), 16 (4.8%) respectively and PSM and BCR rates were not
      statistically different among four approach (P>.05). At the follow-up period, the
      continence rates were 74.4%, 80.4%, 80.5%, and 96.7% (P<.001), and previously
      potent patients' potency rates were 64.3%, 66.6%, 68.1%, and 74.5% (P>.05), in
      classic extrafascial, interfascial, intrafascial, and fascia sparing intrafascial
      prostatectomy, respectively. CONCLUSION: RARP is a safe and feasible technique in
      treatment of localized prostate cancer. Fascia sparing approach has better
      continence rate. This results need to be supported by new prospective, randomized
      studies.

PMID- 24856653
TI  - High-frequency guided ultrasonic waves for hidden defect detection in multi
      layered aircraft structures.
AB  - Aerospace structures often contain multi-layered metallic components where hidden
      defects such as fatigue cracks and localized disbonds can develop, necessitating
      non-destructive testing. Employing standard wedge transducers, high frequency
      guided ultrasonic waves that penetrate through the complete thickness were
      generated in a model structure consisting of two adhesively bonded aluminium
      plates. Interference occurs between the wave modes during propagation along the
      structure, resulting in a frequency dependent variation of the energy through the
      thickness with distance. The wave propagation along the specimen was measured
      experimentally using a laser interferometer. Good agreement with theoretical
      predictions and two-dimensional finite element simulations was found. Significant
      propagation distance with a strong, non-dispersive main wave pulse was achieved.
      The interaction of the high frequency guided ultrasonic waves with small notches
      in the aluminium layer facing the sealant and on the bottom surface of the
      multilayer structure was investigated. Standard pulse-echo measurements were
      conducted to verify the detection sensitivity and the influence of the stand-off
      distance predicted from the finite element simulations. The results demonstrated
      the potential of high frequency guided waves for hidden defect detection at
      critical and difficult to access locations in aerospace structures from a stand
      off distance. 

PMID- 24856654
TI  - Calibration-free portable Young's-modulus tester with isolated langasite
      oscillator.
AB  - A ballpoint-pen-type portable ultrasonic oscillator is developed for quantitative
      measurement of Young's modulus on a solid. It consists of an electrodeless rod
      shaped langasite oscillator with a tungsten-carbide spherical-shaped tip at the
      end, permanent magnets for making a constant force at the contact interface, and
      antennas for exciting and detecting the longitudinal vibration contactlessly. The
      resonance frequency of the oscillator is changed by contact with the specimen,
      reflecting Young's modulus of the specimen at the contact area. The langasite
      oscillator is supported at the nodal points so that its acoustical contact occurs
      only at the specimen, making a calibration-free measurement realistic. Young's
      moduli of various specimens were evaluated within 15% error just by touching the
      specimens with the probe. The error becomes smaller than 10% for lower Young
      modulus materials (<~150 GPa).

PMID- 24856655
TI  - Diagnostic value of elastosonography for thyroid microcarcinoma.
AB  - OBJECTIVE: To assess the diagnostic value of elastosonography for thyroid
      microcarcinoma (TMC), particularly with regard to elasticity score (ES) and
      strain ratio (SR). METHODS: Conventional ultrasound and elastosonography were
      performed for 487 thyroid micronodules before surgery. We set the histology as
      the reference standard. The ES and SR values, as well as their diagnostic
      threshold and efficiency, were compared and analyzed by the receiver-operating
      characteristic (ROC) curve. Additional comparisons between TMC patients with and
      without extracapsular extension were also performed. RESULTS: Statistically
      significant differences (P<0.05) in both ES and SR values were detected among the
      TMC and benign groups. The area under the ROC curve of SR was significantly
      greater than that of ES (0.956 and 0.844, respectively; P<0.05). Using ES?3 and
      SR?3.65 as diagnostic threshold values, the diagnostic sensitivity, specificity,
      and accuracy of ES for differentiating benign and malignant nodules were 79.9%,
      72.3%, and 80.5%, respectively, whereas those of SR were 86.6%, 85.3%, and 89.4%,
      respectively. The maximum diameter, microcalcification status, aspect ratio,
      bilateral cervical lymph node metastasis, and SR values of nodules with
      extracapsular extension (A1 subgroup) were greater than those of nodules without
      extracapsular extension (A2 subgroup). CONCLUSIONS: Elasticity imaging technology
      not only can help differentiate between benign and malignant thyroid micronodules
      but also allow SR values to provide accurate and objective information on tissue
      hardness and to predict TMC extracapsular extension or even bilateral cervical
      lymph node metastasis.

PMID- 24856656
TI  - [The aneurysms of digestive system arteries: three cases].
AB  - The aneurysms of digestive arteries are a rare pathological entity, with a risk
      of rupture associated to a high mortality rate, often asymptomatic, then they are
      discovered incidentally during a exam for other diagnostic purposes. We report
      three cases of digestive aneurysms, one of celiac trunk, one of mesenteric artery
      on behcet disease, and one of splenic artery, which were treated surgically with
      success.

PMID- 24856657
TI  - [Drug dosage adjustment in patients with renal impairment and evaluation of renal
      function: focus on the cardiologic patients].
AB  - Chronic kidney disease is a progressive disease which has become a real public
      health issue. In patients with renal disease, drugs pharmacokinetics may be
      altered. The handling of drugs requires a special attention in these patients.
      Indeed, there is a risk of accumulation and drug overdose if dosage is not
      adjusted to the stage of renal insufficiency. Thus, to achieve a dosage
      adjustment knowing how to evaluate renal function is absolutely necessary.
      Different formulae are available including the Cockcroft and Gault formula aMDRD
      and CKD-EPI. In patients with cardiac issues, it appears that the CKD-EPI formula
      is that of choice in terms of clinical risk stratification. However, some
      summaries of product characteristics (SmPC) of drugs used in cardiology, such as
      Dabigatran((r)), mention the need to use the Cockcroft-Gault, less accurate than
      aMDRD and CKD-EPI, in order to adjust the dose in patients with impaired renal
      function. Standardization of recommendations is necessary to limit disparities in
      dosage and drug exposure according to the formula. SmPCs however, are not the
      only source of information to obtain data on the use of drugs in the renal
      insufficient population. Some other information sources exist, reliable, updated
      and easily accessible. 

PMID- 24856658
TI  - [Factors associated with poor blood pressure control in 253 treated hypertensive
      patients].
AB  - INTRODUCTION: Hypertension is a major public health problem throughout the world.
      The blood pressure control and the decrease of global cardiovascular risk are two
      main goals of the treatment of hypertension. The purpose of this study was to
      determine the proportion and associated factors of uncontrolled hypertension in
      hypertensive patients followed by private cardiologists in Oran. MATERIALS AND
      METHODS: This study included 253 hypertensive patients followed by 7 private
      cardiologists in Oran. Was regarded as uncontrolled high blood pressure, a
      systolic blood pressure (SBP) superior or equal to 140 mmHg and/, or a diastolic
      blood pressure (DBP) superior or equal to 90 mmHg. A logistic regression analysis
      was performed to determine the associated factors with poor blood pressure
      control. RESULTS: The proportion of uncontrolled hypertension was 69.6 % (75.8 %
      of men and 65.8 % of women). Using multivariate analysis, poor blood pressure
      control was found to be associated with salt consumption (ORa=2.71; CI 95 %=[1.42
      5.18]). CONCLUSION: Nutritional actions are required for better blood pressure
      control.

PMID- 24856659
TI  - [Young heart failure: epidemiological, clinical and etiological aspects in the
      teaching hospital Sylvanus Olympio of Lome].
AB  - AIMS: The aim of the study was to analyze the epidemiologic, clinical and
      etiologic aspects of heart failures of the young age to 18 to 45 years. PATIENTS
      AND METHOD: It consisted of a cross-sectional study realized in hospitalization
      in the service of cardiologic of Teaching Hospital Sylvanus Olympio of Lome on 35
      months (January 2009 to November 2012). The completion of a Doppler
      echocardiography was necessary to include the patients in the study. RESULTS: The
      prevalence heart failure in the 45 years old young people to more was of 28.6%.
      The median age of the patients was of 36.5+/-3 years with a sex ratio of 10.7.
      Heart failure was total among 268 patients (71.3%). The electrocardiogram found
      88 patients (23.4%) in complete arrhythmia by auricular fibrillation. Cardiac
      echography found a dilation of the left ventricle among 271 patients (72.1%), a
      systolic dysfunction of left ventricle among 213 patients (56.6%) and an
      intracavitary thrombus among 37 patients (9.8%). The etiologies were:
      hypertension 161 cases (42.8%), heart valve diseases 68 cases (18.1%), the
      peripartum cardiomyopathy 58 cases (15.4%), dilated cardiomyopathy 22 cases
      (5.8%), the alcoholism 12 cases (3.1%), ischaemic heart diseases 10 cases (2.7%),
      congenital heart diseases 10 cases (2.7%), the chronic pulmonary heart 8 cases
      (2.1%), the cardiothyreosis 7 cases (1.8%), the pericardial tamponnade 4 cases
      (1.1%) and myocarditis with VIH 4 cases (1.1%). Hospital lethality was of 16.4%
      (62 patients). CONCLUSION: Heart failure is a serious and frequent pathology in
      Africa. It affects young and active subjects. The causes are dominated by
      hypertension.

PMID- 24856661
TI  - Weight charts of infants dying of sudden infant death in England.
AB  - The organ weights in cases of sudden infant death syndrome (SIDS) and
      undetermined deaths in previously healthy infants do not correspond to "the
      normal range" of organ weights in international standard charts for infants
      currently in use in some institutions. The aim of our study was to ascertain the
      organ weights of infants dying suddenly and unexpectedly in England and for whom
      a cause of death was not found, therefore falling under the category of SIDS or
      undetermined. We collated the organs weights from 2 institutions covering between
      them the South East and North of England including London, Yorkshire, and
      Derbyshire. The cases from The Royal London Hospital were autopsied between 1997
      and 2013, and the cases from Sheffield Children's Hospital were autopsied between
      2006 and 2013. There were 188 babies who had been born at term (62 female and 126
      male) and 26 ex-premature babies (15 female and 11 male). Organs of male babies
      were slightly heavier than those of female babies but as there was no significant
      differences male and female babies were considered together. Comparison with
      standard charts (from 1932 and 1962) and with more recent charts confirmed the
      discrepancy between the older charts commonly in use with more recent
      measurements, including ours. The main reason for these differences is that
      babies in the recent charts were previously healthy babies with no long term
      disease and improved in the health of the population.

PMID- 24856662
TI  - Medial displacement calcaneal osteotomy with posterior tibial tendon
      reconstruction for the flexible flatfoot with symptomatic accessory navicular.
AB  - We investigated the clinical outcomes after medial displacement calcaneal
      osteotomy with reconstruction of the posterior tibial tendon insertion on the
      navicular, in patients with flexible flatfoot with accessory navicular symptoms.
      From December 2008 to July 2011, 16 patients (21 feet) with a flexible flatfoot,
      symptomatic accessory navicular, and obvious heel valgus underwent medial
      displacement calcaneal osteotomy and reconstruction with posterior tibial tendon
      insertion on the navicular bone. The patients were evaluated preoperatively, 6
      weeks and 3, 6, and 12 months postoperatively, and every 6 months thereafter. The
      clinical examination was undertaken using the American Orthopaedic Foot and Ankle
      Society ankle and midfoot scores. The radiologic assessments included the arch
      height, calcaneus inclination angle, talocalcaneal angle, and talar first
      metatarsal angle on the lateral weightbearing radiograph. The talocalcaneal angle
      and talar first metatarsal angle was assessed on the anteroposterior view of the
      weightbearing foot. Heel valgus alignment was assessed on the axial hindfoot
      radiographs. The mean follow-up duration was 28.5 months (range 18 to 48). All
      patients were satisfied with the clinical results and were pain free 6 months
      postoperatively. No cases of wound infection or nerve injury developed. The mean
      American Orthopaedic Foot and Ankle Society score improved from 53.3 +/- 6.5 to
      90.8 +/- 1.4 at the last follow-up visit (p < .01). The improvements in all
      radiographic parameters were statistically significant between the preoperative
      and last follow-up examinations (p < .01). The heel valgus of all patients was
      corrected. Our results have shown that medial displacement calcaneal osteotomy
      with reconstruction of the posterior tibial tendon insertion on the navicular
      bone is an effective treatment of flexible flatfoot with symptomatic accessory
      navicular, associated with excellent clinical outcomes and correction of the
      deformity.

PMID- 24856660
TI  - MERS coronaviruses in dromedary camels, Egypt.
AB  - We identified the near-full-genome sequence (29,908 nt, >99%) of Middle East
      respiratory syndrome coronavirus (MERS-CoV) from a nasal swab specimen from a
      dromedary camel in Egypt. We found that viruses genetically very similar to human
      MERS-CoV are infecting dromedaries beyond the Arabian Peninsula, where human MERS
      CoV infections have not yet been detected. 

PMID- 24856664
TI  - Double calcaneal osteotomy with percutaneous Steinmann pin fixation as part of
      treatment for flexible flatfoot deformity: a review of consecutive cases
      highlighting our experience with pin fixation.
AB  - Surgical correction of flexible flatfoot deformity and posterior tibial tendon
      dysfunction has been extensively reported in published studies. When appropriate,
      calcaneal osteotomies for flatfoot correction have been a favorite of foot and
      ankle surgeons because of the corrective power achieved without the need to fuse
      any rearfoot joints. The medial displacement calcaneal osteotomy and Evans
      calcaneal osteotomy, together termed the double calcaneal osteotomy, have been
      reported several times by various investigators with a wide variety of fixation
      options. We undertook an institutional review board-approved retrospective review
      of 9 consecutive patients (11 feet), who had undergone double calcaneal osteotomy
      with 2 percutaneous Steinmann pin fixation for the correction of flexible
      flatfoot deformity, with or without posterior tibial tendon dysfunction. All
      patients had radiographic evidence of bone healing of the posterior calcaneal
      osteotomy and incorporation of the Evans osteotomy bone graft at 6 weeks and
      demonstrated clinical healing at 6 weeks. All patients had 2 percutaneous
      Steinmann pins placed through both osteotomies, and these were removed an average
      of 6 weeks postoperatively. No patient developed pin site complications. The only
      complication noted was sural neuritis, which was likely incision related. No
      patients had delayed union or nonunion, and we did not identify any graft
      shifting postoperatively. The present retrospective series highlights our
      experience with 2 percutaneous Steinmann pin fixation, demonstrating equal or
      better results than many previous published fixation methods for double calcaneal
      osteotomy. It is cost-effective and minimizes the potential risk of iatrogenic
      Achilles pathologic features associated with screw fixation. 

PMID- 24856663
TI  - Landing on your own two feet: a case report of bilateral calcaneus and open pilon
      fractures.
AB  - High energy fractures of the distal tibial plafond and calcaneus have been
      associated with high functional morbidity and wound complications. Although both
      of these fractures result from a similar mechanism, they have rarely been
      reported to occur on an ipsilateral extremity. The combination of these 2
      injuries on the same extremity would increase the likelihood of an adverse
      surgical or functional outcome. We present the case and management strategy of a
      43-year-old male with bilateral open pilon fractures and closed calcaneal
      fractures after falling from a height. A staged protocol was used for the
      bilateral pilon fractures, with external fixation until operative fixation on day
      9. Nonoperative management of the calcaneal fractures resulted in a successful
      functional outcome at 10 months of follow-up. Treatment of this fracture pattern
      must incorporate the condition of the soft tissues, an understanding of the
      fractures, and minimize patient risk factors to optimize the functional and
      surgical outcomes.

PMID- 24856665
TI  - Oleanolic acid induces metabolic adaptation in cancer cells by activating the AMP
      activated protein kinase pathway.
AB  - Cancer cells are well-known to require a constant supply of protein, lipid, RNA,
      and DNA via altered metabolism for accelerated cell proliferation. Targeting
      metabolic pathways is, therefore, a promising therapeutic strategy for cancers.
      Oleanolic acid (OA) is widely distributed in dietary and medicinal plants and
      displays a selective cytotoxicity to cancer cells, primarily by inducing
      apoptosis and cell cycle arrest. This study investigated if OA inhibited growth
      of tumor cells by affecting their metabolism. OA was found to activate AMP
      activated protein kinase (AMPK), the master regulator of metabolism, in prostate
      cancer cell line PC-3 and breast cancer cell line MCF-7. AMPK activation is
      required for the antitumor activity of OA on cancer cells. Lipogenesis, protein
      synthesis, and aerobic glycolysis were inhibited in cancer cells treated with OA,
      in an AMPK activation-dependent manner. The metabolic alteration was shown to
      mediate the tumor suppressor activity of OA on cancer cells. Collectively, this
      study provides evidence that OA, as a widely distributed nutritional component,
      is able to exert antitumor function by interfering in the metabolic pathway in
      cancer cells. This finding should encourage researchers to study if affecting
      cancer metabolism is a common mechanism by which nutritional compounds suppress
      cancers. 

PMID- 24856666
TI  - Attempt toward a development of aquatic exercise device for gait disorders.
AB  - Abstract Purpose: To develop an aquatic exercise device to facilitate locomotive
      motor output and achieve repetitive physiological gait patterns to improve
      movement dysfunctions. Methods: A custom designed leg movement apparatus (LMA)
      consisted of closed 4-linkage mechanisms and one-length changeable link using a
      spring. Three-dimensional motions and electromyographic (EMG) activities were
      recorded in eight healthy subjects to evaluate the reproducibility of the
      physiological gait patterns using the LMA with or without a spring apparatus in
      water. Results: Using the LMA with a spring apparatus compared to walking in
      water, the foot trajectories and the time course of the elevation angles in each
      lower limb joint kinematics were preserved. The time-series of the EMG showed
      reciprocal modulation between agonist and antagonist muscle groups in the hip and
      ankle joints. However, the amplitudes of the tibialis anterior muscle in the
      first half and rectus femoris in the last half of the movement cycle were reduced
      using the LMA with a spring apparatus. Conclusion: We developed a novel aquatic
      exercise device to reproduce physiological gait patterns. The LMA with a spring
      apparatus would be particularly valuable in therapy for movement dysfunctions to
      facilitate locomotive motor outputs. Implications for Rehabilitation The leg
      movement apparatus with spring for underwater use (LMA) would be effective gait
      training to induce the locomotor-like EMG activities. Hydrotherapy with the LMA
      has advantages over the partial body weight support treadmill training on land
      with a robotic device; (1) the LMA is electrically and mechanically safe, and (2)
      the LMA would require self-effort to generate the gait pattern for movement
      disorders, or also enable passive gait training by the physiotherapists.

PMID- 24856667
TI  - [Less bends, less pressure, more accuracy. Transseptal access to ablate left
      accessory pathways].

PMID- 24856668
TI  - Extended pancreatectomy in pancreatic ductal adenocarcinoma: definition and
      consensus of the International Study Group for Pancreatic Surgery (ISGPS).
AB  - BACKGROUND: Complete macroscopic tumor resection is one of the most relevant
      predictors of long-term survival in pancreatic ductal adenocarcinoma. Because
      locally advanced pancreatic tumors can involve adjacent organs, "extended"
      pancreatectomy that includes the resection of additional organs may be needed to
      achieve this goal. Our aim was to develop a common consistent terminology to be
      used in centers reporting results of pancreatic resections for cancer. METHODS:
      An international panel of pancreatic surgeons working in well-known, high-volume
      centers reviewed the literature on extended pancreatectomies and worked together
      to establish a consensus on the definition and the role of extended
      pancreatectomy in pancreatic cancer. RESULTS: Macroscopic (R1) and microscopic
      (R0) complete tumor resection can be achieved in patients with locally advanced
      disease by extended pancreatectomy. Operative time, blood loss, need for blood
      transfusions, duration of stay in the intensive care unit, and hospital
      morbidity, and possibly also perioperative mortality are increased with extended
      resections. Long-term survival is similar compared with standard resections but
      appears to be better compared with bypass surgery or nonsurgical palliative
      chemotherapy or chemoradiotherapy. It was not possible to identify any clear
      prognostic criteria based on the specific additional organ resected. CONCLUSION:
      Despite increased perioperative morbidity, extended pancreatectomy is warranted
      in locally advanced disease to achieve long-term survival in pancreatic ductal
      adenocarcinoma if macroscopic clearance can be achieved. Definitions of extended
      pancreatectomies for locally advanced disease (and not distant metastatic
      disease) are established that are crucial for comparison of results of future
      trials across different practices and countries, in particular for those using
      neoadjuvant therapy.

PMID- 24856670
TI  - Commentary on: why was there no mention of informed consent and ethics committee
      approval in a prospective trial?

PMID- 24856669
TI  - Lack of identifiable biologic behavior in a series of porcine mesh explants.
AB  - INTRODUCTION: Biologic matrices used in abdominal wall reconstruction are
      purported to undergo remodeling into connective tissue resembling native
      collagen. Key steps in that process include inflammatory response at the
      mesh/tissue interface, cellular penetration, and neovascularization of the
      matrix, followed by fibroblast proliferation and collagen deposition. We aimed to
      examine the concept of biologic mesh remodeling/regeneration in a series of
      explanted porcine biologic meshes. MATERIALS AND METHODS: A cohort of patients
      who underwent removal of porcine biologic mesh was identified in a prospective
      database. Mesh/tissue samples were analyzed using standard hematoxylin/eosin and
      Masson's trichrome staining. Main outcome measures included: inflammatory
      response at the mesh/tissue interface, foreign body reaction (FBR), cellular
      penetration, neovascularization, and new collagen deposition. All evaluations
      were performed by a blinded senior pathologist using established grading scales.
      RESULTS: A total of 14 cases with implant time ranging from 4 to 33 months were
      identified and analyzed. All meshes were placed as intraperitoneal underlay.
      There were 7 non-cross-linked and 7 cross-linked grafts. Cross-linked grafts were
      associated with mild FBR and moderate fibrous capsule formation. Similarly, non
      cross-linked grafts had mild-to-moderate FBR and encapsulation. Furthermore, non
      cross-linked grafts were associated with no neovascularization and minimal
      peripheral mesh neocellularization. Cross-linked grafts demonstrated neither
      neovascularization nor neocellularization. Although no grafts were associated
      with any quantifiable new collagen deposition within the porcine biologic matrix,
      minimal biodegradation/remodeling was observed at the periphery of the non-cross
      linked grafts only. CONCLUSION: The biologic behavior of porcine meshes is
      predicated on their ability to undergo mesh remodeling with resorption and new
      collagen deposition. In the largest series of human biologic explants, we
      detected no evidence of xenograft remodeling, especially in the cross-linked
      group. Although underlay mesh placement and other patient factors may have
      contributed to our findings, the concept of porcine biologic mesh regeneration
      does not seem to be prevalent in the clinical setting.

PMID- 24856671
TI  - Presentation of the Julius M. Friedenwald Medal to Nicholas F. LaRusso, MD.

PMID- 24856676
TI  - Delayed-choice quantum eraser with thermal light.
AB  - We report a random delayed-choice quantum eraser experiment. In a Young's double
      slit interferometer, the which-slit information is learned from the photon-number
      fluctuation correlation of thermal light. The reappeared interference indicates
      that the which-slit information of a photon, or wave packet, can be "erased" by a
      second photon or wave packet, even after the annihilation of the first. Different
      from an entangled photon pair, the jointly measured two photons, or wave packets,
      are just two randomly distributed and randomly created photons of a thermal
      source that fall into the coincidence time window. The experimental observation
      can be explained as a nonlocal interference phenomenon in which a random photon
      or wave packet pair, interferes with the pair itself at distance. 

PMID- 24856677
TI  - Observing interferences between past and future quantum states in resonance
      fluorescence.
AB  - The fluorescence of a resonantly driven superconducting qubit is measured in the
      time domain, providing a weak probe of the qubit dynamics. Prior preparation and
      final, single-shot measurement of the qubit allows us to average fluorescence
      records conditionally on past and future knowledge. The resulting interferences
      reveal purely quantum features characteristic of weak values. We demonstrate
      conditional averages that go beyond classical boundaries and probe directly the
      jump operator associated with relaxation. The experimental results are remarkably
      captured by a recent theory, which generalizes quantum mechanics to open quantum
      systems whose past and future are known. 

PMID- 24856674
TI  - Identification of 1-({[1-(4-fluorophenyl)-5-(2-methoxyphenyl)-1H-pyrazol-3
      yl]carbonyl}amino)cyclohexane carboxylic acid as a selective nonpeptide
      neurotensin receptor type 2 compound.
AB  - Compounds active at neurotensin receptors (NTS1 and NTS2) exert analgesic effects
      on different types of nociceptive modalities, including thermal, mechanical, and
      chemical stimuli. The NTS2 preferring peptide JMV-431 (2) and the NTS2 selective
      nonpeptide compound levocabastine (6) have been shown to be effective in
      relieving the pain associated with peripheral neuropathies. With the aim of
      identifying novel nonpeptide compounds selective for NTS2, we examined analogues
      of SR48692 (5a) using a FLIPR calcium assay in CHO cells stably expressing rat
      NTS2. This led to the discovery of the NTS2 selective nonpeptide compound 1-({[1
      (4-fluorophenyl)-5-(2-methoxyphenyl)-1H-pyrazol-3-yl]carbonyl}amino)cyclohexane
      carboxylic acid (NTRC-739, 7b) starting from the nonselective compound 5a. 

PMID- 24856675
TI  - Efficacy of ruxolitinib for myelofibrosis.
AB  - INTRODUCTION: The discovery of the activating JAK2 V617F mutation in patients
      with myelofibrosis (MF) led to the development of JAK2 inhibitors. The first such
      inhibitor to enter clinical trials was ruxolitinib . This review summarizes
      preclinical and clinical data of ruxolitinib in MF. AREAS COVERED: A literature
      search through Medline employing the terms 'ruxolitinib,' 'INCB018424' and
      'myelofibrosis' was undertaken. The results from Phase I/II studies in patients
      with MF showed that ruxolitinib led to durable improvements in splenomegaly, and
      symptoms associated with MF. Two Phase III trials have compared ruxolitinib
      against placebo and best available therapy, and in both studies ruxolitinib
      demonstrated superior rates of spleen control and symptom improvement, and
      additional analysis demonstrated a survival benefit with ruxolitinib treatment.
      The main toxicities seen with ruxolitinib are cytopenias, which are managed with
      dose adjustments. Recent reports documented sporadic cases of immunosuppression
      related infections. Ruxolitinib is the first drug ever approved for the therapy
      of patients with MF. EXPERT OPINION: Understanding the factors that predict the
      rate and duration of response to ruxolitinib would improve our ability to manage
      patients treated with this medication. Clinical trials combining ruxolitinib with
      novel compounds that are also active in MF will further improve therapy for this
      disease.

PMID- 24856678
TI  - Fundamental, multipole, and half-vortex gap solitons in spin-orbit coupled Bose
      Einstein condensates.
AB  - Using the parity and time reversal symmetries of a two-dimensional spin-orbit
      coupled Bose-Einstein condensate in a lattice created by the Zeeman field, we
      identify and find numerically various families of localized solutions, including
      multipole and half-vortex solitons. The obtained solutions may exist at any
      direction of the gauge field with respect to the lattice and can be found either
      in finite gaps (for repulsive interatomic interactions) or in a semi-infinite gap
      (for attractive interactions). The existence of half-vortices requires higher
      symmetry (the reflection with respect to the field direction). Stability of these
      modes makes them feasible for experimental observation. 

PMID- 24856679
TI  - Quantifying Einstein-Podolsky-Rosen steering.
AB  - Einstein-Podolsky-Rosen steering is a form of bipartite quantum correlation that
      is intermediate between entanglement and Bell nonlocality. It allows for
      entanglement certification when the measurements performed by one of the parties
      are not characterized (or are untrusted) and has applications in quantum key
      distribution. Despite its foundational and applied importance, Einstein-Podolsky
      Rosen steering lacks a quantitative assessment. Here we propose a way of
      quantifying this phenomenon and use it to study the steerability of several
      quantum states. In particular, we show that every pure entangled state is
      maximally steerable and the projector onto the antisymmetric subspace is
      maximally steerable for all dimensions; we provide a new example of one-way
      steering and give strong support that states with positive-partial transposition
      are not steerable. 

PMID- 24856680
TI  - Hybrid quantum magnetism in circuit QED: from spin-photon waves to many-body
      spectroscopy.
AB  - We introduce a model of quantum magnetism induced by the nonperturbative exchange
      of microwave photons between distant superconducting qubits. By interconnecting
      qubits and cavities, we obtain a spin-boson lattice model that exhibits a quantum
      phase transition where both qubits and cavities spontaneously polarize. We
      present a many-body ansatz that captures this phenomenon all the way, from a the
      perturbative dispersive regime where photons can be traced out, to the
      nonperturbative ultrastrong coupling regime where photons must be treated on the
      same footing as qubits. Our ansatz also reproduces the low-energy excitations,
      which are described by hybridized spin-photon quasiparticles, and can be probed
      spectroscopically from transmission experiments in circuit QED, as shown by
      simulating a possible experiment by matrix-product-state methods. 

PMID- 24856681
TI  - Permutationally invariant part of a density matrix and nonseparability of N-qubit
      states.
AB  - We consider the concept of "the permutationally invariant (PI) part of a density
      matrix," which has proven very useful for both efficient quantum state estimation
      and entanglement characterization of N-qubit systems. We show here that the
      concept is, in fact, basis dependent but that this basis dependence makes it an
      even more powerful concept than has been appreciated so far. By considering the
      PI part rho(PI) of a general (mixed) N-qubit state rho, we obtain (i) strong
      bounds on quantitative nonseparability measures, (ii) a whole hierarchy of
      multipartite separability criteria (one of which entails a sufficient criterion
      for genuine N-partite entanglement) that can be experimentally determined by just
      2N+1 measurement settings, (iii) a definition of an efficiently measurable degree
      of separability, which can be used for quantifying a novel aspect of decoherence
      of N qubits, and (iv) an explicit example that shows there are, for increasing N,
      genuinely N-partite entangled states lying closer and closer to the maximally
      mixed state. Moreover, we show that if the PI part of a state is k nonseparable,
      then so is the actual state. We further argue to add as requirement on any
      multipartite entanglement measure E that it satisfy E(rho)>=E(rho(PI)), even
      though the operation that maps rho->rho(PI) is not local.

PMID- 24856682
TI  - Entropy production and fluctuation theorems for Langevin processes under
      continuous non-Markovian feedback control.
AB  - Continuous feedback control of Langevin processes may be non-Markovian due to a
      time lag between the measurement and the control action. We show that this
      requires one to modify the basic relation between dissipation and time reversal
      and to include a contribution arising from the noncausal character of the reverse
      process. We then propose a new definition of the quantity measuring the
      irreversibility of a path in a nonequilibrium stationary state, which can also be
      regarded as the trajectory-dependent total entropy production. This leads to an
      extension of the second law, which takes a simple form in the long-time limit. As
      an illustration, we apply the general approach to linear systems that are both
      analytically tractable and experimentally relevant. 

PMID- 24856683
TI  - Nonequilibrium solutions of the Boltzmann equation under the action of an
      external force.
AB  - We construct a novel class of exact solutions to the Boltzmann equation, in both
      its classical and quantum formulation, for arbitrary collision laws. When the
      system is subjected to a specific external forcing, the precise form of which is
      worked out, nonequilibrium dampingless solutions are admissible. They do not
      contradict the H theorem, but are constructed from its requirements.
      Interestingly, these solutions hold for time-dependent confinement. We exploit
      them, in a reverse-engineering perspective, to work out a protocol that shortcuts
      any adiabatic transformation between two equilibrium states in an arbitrarily
      short time span, for an interacting system. Particle simulations of the direct
      Monte Carlo type fully corroborate the analytical predictions. 

PMID- 24856684
TI  - Work output and efficiency at maximum power of linear irreversible heat engines
      operating with a finite-sized heat source.
AB  - We formulate the work output and efficiency for linear irreversible heat engines
      working between a finite-sized hot heat source and an infinite-sized cold heat
      reservoir until the total system reaches the final thermal equilibrium state with
      a uniform temperature. We prove that when the heat engines operate at the maximum
      power under the tight-coupling condition without heat leakage the work output is
      just half of the exergy, which is known as the maximum available work extracted
      from a heat source. As a consequence, the corresponding efficiency is also half
      of its quasistatic counterpart. 

PMID- 24856685
TI  - Energy versus information based estimations of dissipation using a pair of
      magnetic colloidal particles.
AB  - Using the framework of stochastic thermodynamics, we present an experimental
      study of a doublet of magnetic colloidal particles that is manipulated by a time
      dependent magnetic field. Because of hydrodynamic interactions, each bead
      experiences a state-dependent friction, which we characterize using a
      hydrodynamic model. In this work, we compare two estimates of the dissipation in
      this system: the first one is energy based since it relies on the measured
      interaction potential, while the second one is information based since it uses
      only the information content of the trajectories. While the latter only offers a
      lower bound of the former, we find it to be simple to implement and of general
      applicability to more complex systems. 

PMID- 24856686
TI  - Nonequilibrium statistical mechanics of the heat bath for two Brownian particles.
AB  - We propose a new look at the heat bath for two Brownian particles, in which the
      heat bath as a "system" is both perturbed and sensed by the Brownian particles.
      Nonlocal thermal fluctuations give rise to bath-mediated static forces between
      the particles. Based on the general sum rule of the linear response theory, we
      derive an explicit relation linking these forces to the friction kernel
      describing the particles' dynamics. The relation is analytically confirmed in the
      case of two solvable models and could be experimentally challenged. Our results
      point out that the inclusion of the environment as a part of the whole system is
      important for micron- or nanoscale physics. 

PMID- 24856689
TI  - Enhanced nonperturbative effects through the collinear anomaly.
AB  - We show that nonperturbative effects are logarithmically enhanced for transverse
      momentum-dependent observables such as qT spectra of electroweak bosons in
      hadronic collisions and jet broadening at e+ e- colliders. This enhancement
      arises from the collinear anomaly, a mechanism characteristic for transverse
      observables, which induces logarithmic dependence on the hard scale in the
      product of the soft and collinear matrix elements. Our analysis is based on an
      operator product expansion and provides, for the first time, a systematic, model
      independent way to study nonperturbative effects for this class of observables.
      For the case of jet broadening, we relate the leading correction to the
      nonperturbative shift of the thrust distribution.

PMID- 24856690
TI  - Polarizations of chic1 and chic2 in prompt production at the LHC.
AB  - Prompt chic production at hadron colliders may provide a unique test for the
      color-octet mechanism in nonrelativistic QCD. We present an analysis for the
      polarization observables of chic1 and chic2 at next-to-leading order in alphaS
      and propose to measure them at the LHC, which is expected to be important for
      testing the validity of nonrelativistic QCD.

PMID- 24856692
TI  - Neutral weak current two-body contributions in inclusive scattering from 12C.
AB  - An ab initio calculation of the sum rules of the neutral weak response functions
      in 12C is reported, based on a realistic Hamiltonian, including two- and three
      nucleon potentials, and on realistic currents, consisting of one- and two-body
      terms. We find that the sum rules of the response functions associated with the
      longitudinal and transverse components of the (spacelike) neutral current are
      largest and that a significant portion (?30%) of the calculated strength is due
      to two-body terms. This fact may have implications for the MiniBooNE and other
      neutrino quasielastic scattering data on nuclei.

PMID- 24856691
TI  - Separated response function ratios in exclusive, forward pi(+/-)
      electroproduction.
AB  - The study of exclusive pi(+/-) electroproduction on the nucleon, including
      separation of the various structure functions, is of interest for a number of
      reasons. The ratio RL=sigmaL(pi-)/sigmaL(pi+) is sensitive to isoscalar
      contamination to the dominant isovector pion exchange amplitude, which is the
      basis for the determination of the charged pion form factor from
      electroproduction data. A change in the value of RT=sigmaT(pi-)/sigmaT(pi+) from
      unity at small -t, to 1/4 at large -t, would suggest a transition from coupling
      to a (virtual) pion to coupling to individual quarks. Furthermore, the mentioned
      ratios may show an earlier approach to perturbative QCD than the individual cross
      sections. We have performed the first complete separation of the four unpolarized
      electromagnetic structure functions above the dominant resonances in forward,
      exclusive pi(+/-) electroproduction on the deuteron at central Q(2) values of
      0.6, 1.0, 1.6  GeV(2) at W=1.95  GeV, and Q(2)=2.45  GeV(2) at W=2.22  GeV. Here,
      we present the L and T cross sections, with emphasis on RL and RT, and compare
      them with theoretical calculations. Results for the separated ratio RL indicate
      dominance of the pion-pole diagram at low -t, while results for RT are consistent
      with a transition between pion knockout and quark knockout mechanisms.

PMID- 24856693
TI  - Cooling dynamics of photoexcited C6(-) and C6H(-).
AB  - We report conclusive evidence of an efficient cooling mechanism via the
      electronic radiative transitions of hot small molecular anions isolated in
      vacuum. We stored C6(-) and C6H(-) in an ion storage ring and observed laser
      induced electron detachment with delays up to several milliseconds. The terminal
      hydrogen atom caused a drastic change in the decay profiles. The decay of
      photoexcited C6H(-) is slow and nonexponential, which can be explained by
      depletion cooling, whereas that for C6(-) occurs extremely fast, on a time scale
      below 0.1 ms and can only be explained by electronic radiative cooling via low
      lying electronic excited states.

PMID- 24856694
TI  - Demonstration of a strong Rydberg blockade in three-atom systems with anisotropic
      interactions.
AB  - We study the Rydberg blockade in a system of three atoms arranged in different
      two-dimensional geometries (linear and triangular configurations). In the strong
      blockade regime, we observe high-contrast, coherent collective oscillations of
      the single excitation probability and an almost perfect van der Waals blockade.
      Our data are consistent with a total population in doubly and triply excited
      states below 2%. In the partial blockade regime, we directly observe the
      anisotropy of the van der Waals interactions between |nD> Rydberg states in the
      triangular configuration. A simple model that only uses independently measured
      two-body van der Waals interactions fully reproduces the dynamics of the system
      without any adjustable parameter. These results are extremely promising for
      scalable quantum information processing and quantum simulation with neutral
      atoms.

PMID- 24856695
TI  - Hidden charge states in soft-x-ray laser-produced nanoplasmas revealed by
      fluorescence spectroscopy.
AB  - Highly charged ions are formed in the center of composite clusters by strong free
      electron laser pulses and they emit fluorescence on a femtosecond time scale
      before competing recombination leads to neutralization of the nanoplasma core. In
      contrast to mass spectrometry that detects remnants of the interaction,
      fluorescence in the extreme ultraviolet spectral range provides fingerprints of
      transient states of high energy density matter. Spectra from clusters consisting
      of a xenon core and a surrounding argon shell show that a small fraction of the
      fluorescence signal comes from multiply charged xenon ions in the cluster core.
      Initially, these ions are as highly charged as the ions in the outer shells of
      pure xenon clusters with charge states up to at least 11+. 

PMID- 24856687
TI  - Precise measurement of the neutrino mixing parameter theta23 from muon neutrino
      disappearance in an off-axis beam.
AB  - New data from the T2K neutrino oscillation experiment produce the most precise
      measurement of the neutrino mixing parameter theta23. Using an off-axis neutrino
      beam with a peak energy of 0.6 GeV and a data set corresponding to 6.57*10(20)
      protons on target, T2K has fit the energy-dependent nuMU oscillation probability
      to determine oscillation parameters. The 68% confidence limit on sin(2)(theta23)
      is 0.514(-0.056)(+0.055) (0.511+/-0.055), assuming normal (inverted) mass
      hierarchy. The best-fit mass-squared splitting for normal hierarchy is
      Deltam32(2)=(2.51+/-0.10)*10(-3)  eV(2)/c(4) (inverted hierarchy:
      Deltam13(2)=(2.48+/-0.10)*10(-3)  eV(2)/c(4)). Adding a model of multinucleon
      interactions that affect neutrino energy reconstruction is found to produce only
      small biases in neutrino oscillation parameter extraction at current levels of
      statistical uncertainty.

PMID- 24856696
TI  - Electrically injected photon-pair source at room temperature.
AB  - One of the main challenges for future quantum information technologies is the
      miniaturization and integration of high performance components in a single chip.
      In this context, electrically driven sources of nonclassical states of light have
      a clear advantage over optically driven ones. Here we demonstrate the first
      electrically driven semiconductor source of photon pairs working at room
      temperature and telecom wavelengths. The device is based on type-II intracavity
      spontaneous parametric down-conversion in an AlGaAs laser diode and generates
      pairs at 1.57  MUm. Time-correlation measurements of the emitted pairs give an
      internal generation efficiency of 7*10(-11)  pairs/injected electron. The
      capability of our platform to support the generation, manipulation, and detection
      of photons opens the way to the demonstration of massively parallel systems for
      complex quantum operations.

PMID- 24856697
TI  - Relative refractory period in an excitable semiconductor laser.
AB  - We report on experimental evidence of neuronlike excitable behavior in a
      micropillar laser with saturable absorber. We show that under a single pulsed
      perturbation the system exhibits subnanosecond response pulses and analyze the
      role of the laser bias pumping. Under a double pulsed excitation we study the
      absolute and relative refractory periods, similarly to what can be found in
      neural excitability, and interpret the results in terms of a dynamical inhibition
      mediated by the carrier dynamics. These measurements shed light on the analogy
      between optical and biological neurons and pave the way to fast spike-time coding
      based optical systems with a speed several orders of magnitude faster than their
      biological or electronic counterparts. 

PMID- 24856698
TI  - Conductive coupling of split ring resonators: a path to THz metamaterials with
      ultrasharp resonances.
AB  - We report on a novel metamaterial structure that sustains extremely sharp
      resonances in the terahertz domain. This system involves two conductively coupled
      split ring resonators that together exhibit a novel resonance, in broad analogy
      to the antiphase mode of the so-called Huygens coupled pendulum. Even though this
      resonance is in principle forbidden in each individual symmetric split ring, our
      experiments show that this new coupled mode can sustain quality factors that are
      more than one order of magnitude larger than those of conventional split ring
      arrangements. Because of the universality of the metamaterial response, the
      design principle we present here can be applied across the entire electromagnetic
      spectrum and to various metamaterial resonators. 

PMID- 24856699
TI  - Gravity-driven enhancement of heavy particle clustering in turbulent flow.
AB  - Heavy particles suspended in a turbulent flow settle faster than in a still
      fluid. This effect stems from a preferential sampling of the regions where the
      fluid flows downward and is quantified here as a function of the level of
      turbulence, of particle inertia, and of the ratio between gravity and turbulent
      accelerations. By using analytical methods and detailed, state-of-the-art
      numerical simulations, settling is shown to induce an effective horizontal two
      dimensional dynamics that increases clustering and reduce relative velocities
      between particles. These two competing effects can either increase or decrease
      the geometrical collision rates between same-size particles and are crucial for
      realistic modeling of coalescing particles. 

PMID- 24856700
TI  - Subcritical equilibria in Taylor-Couette flow.
AB  - Nonlinear equilibrium states characterized by strongly localized vortex pairs are
      calculated in the linearly stable parameter region of counterrotating Taylor
      Couette flow. These subcritical states are rotating waves whose region of
      existence is consistent with the critical threshold for relaminarization observed
      in experiments. For sufficiently rapid outer cylinder rotation the solutions
      extend beyond the static inner cylinder case to corotation, thus exceeding, for
      the first time, the boundary defined by the inviscid Rayleigh's stability
      criterion. 

PMID- 24856701
TI  - Exploration of the transition from the hydrodynamiclike to the strongly kinetic
      regime in shock-driven implosions.
AB  - Clear evidence of the transition from hydrodynamiclike to strongly kinetic shock
      driven implosions is, for the first time, revealed and quantitatively assessed.
      Implosions with a range of initial equimolar D3He gas densities show that as the
      density is decreased, hydrodynamic simulations strongly diverge from and
      increasingly overpredict the observed nuclear yields, from a factor of ~2 at 3.1 
      mg/cm3 to a factor of 100 at 0.14  mg/cm3. (The corresponding Knudsen number, the
      ratio of ion mean-free path to minimum shell radius, varied from 0.3 to 9;
      similarly, the ratio of fusion burn duration to ion diffusion time, another
      figure of merit of kinetic effects, varied from 0.3 to 14.) This result is shown
      to be unrelated to the effects of hydrodynamic mix. As a first step to garner
      insight into this transition, a reduced ion kinetic (RIK) model that includes
      gradient-diffusion and loss-term approximations to several transport processes
      was implemented within the framework of a one-dimensional radiation-transport
      code. After empirical calibration, the RIK simulations reproduce the observed
      yield trends, largely as a result of ion diffusion and the depletion of the
      reacting tail ions.

PMID- 24856702
TI  - Plasma heating by electric field compression.
AB  - Plasma heating by compression of electric fields is proposed. It is shown that
      periodic cycles of external compression followed by the free expansion of
      electric fields in the plasma cause irreversible, collisionless plasma heating
      and corresponding entropy generation. As a demonstration of general ideas and
      scalings, the heating is shown in the case of a dusty plasma, where electric
      fields are created due to the presence of charged dust. The method is expected to
      work in the cases of compression of low frequency or dc electric fields created
      by other methods. Applications to high power laser heating of plasmas using this
      scheme are discussed. 

PMID- 24856703
TI  - First measurements of hydrodynamic instability growth in indirectly driven
      implosions at ignition-relevant conditions on the National Ignition Facility.
AB  - Ignition experiments have shown an anomalous susceptibility to hydrodynamic
      instability growth. To help understand these results, the first hydrodynamic
      instability growth measurements in indirectly driven implosions on the National
      Ignition Facility were performed at ignition conditions with peak radiation
      temperatures up to ~300  eV. Plastic capsules with two-dimensional preimposed,
      sinusoidal outer surface modulations of initial wavelengths of 240 (corresponding
      to a Legendre mode number of 30), 120 (mode 60), and 80  MUm (mode 90) were
      imploded by using actual low-adiabat ignition laser pulses. The measured growth
      was in excellent agreement, validating 2D hydra simulations for the most
      dangerous modes in the acceleration phase. These results reinforce confidence in
      the predictive capability of calculations that are paramount to illuminating the
      path toward ignition. 

PMID- 24856704
TI  - New edge coherent mode providing continuous transport in long-pulse H-mode
      plasmas.
AB  - An electrostatic coherent mode near the electron diamagnetic frequency (20-90
      kHz) is observed in the steep-gradient pedestal region of long pulse H-mode
      plasmas in the Experimental Advanced Superconducting Tokamak, using a newly
      developed dual gas-puff-imaging system and diamond-coated reciprocating probes.
      The mode propagates in the electron diamagnetic direction in the plasma frame
      with poloidal wavelength of ~8  cm. The mode drives a significant outflow of
      particles and heat as measured directly with the probes, thus greatly
      facilitating long pulse H-mode sustainment. This mode shows the nature of
      dissipative trapped electron mode, as evidenced by gyrokinetic turbulence
      simulations. 

PMID- 24856705
TI  - Observation of dipole-induced spin texture in an 87Rb Bose-Einstein condensate.
AB  - We report the formation of spin texture resulting from the magnetic dipole-dipole
      interaction in a spin-2 87Rb Bose-Einstein condensate. The spinor condensate is
      prepared in the transversely polarized spin state and the time evolution is
      observed under a magnetic field of 90 mG with a gradient of 3  mG/cm using Stern
      Gerlach imaging. The experimental results are compared with numerical simulations
      of the Gross-Pitaevskii equation, which reveals that the observed spatial
      modulation of the longitudinal magnetization is due to the spin precession in an
      effective magnetic field produced by the dipole-dipole interaction. These results
      show that the dipole-dipole interaction has considerable effects even on spinor
      condensates of alkali metal atoms.

PMID- 24856706
TI  - Universal fractional noncubic power law for density of metallic glasses.
AB  - As a fundamental property of a material, density is controlled by the interatomic
      distances and the packing of microscopic constituents. The most prominent
      atomistic feature in a metallic glass (MG) that can be measured is its principal
      diffraction peak position (q1) observable by x-ray, electron, or neutron
      diffraction, which is closely associated with the average interatomic distance in
      the first shell. Density (and volume) would naturally be expected to vary under
      compression in proportion to the cube of the one-dimensional interatomic
      distance. However, by using high pressure as a clean tuning parameter and high
      resolution in situ techniques developed specifically for probing the density of
      amorphous materials, we surprisingly found that the density of a MG varies with
      the 5/2 power of q1, instead of the expected cubic relationship. Further studies
      of MGs of different compositions repeatedly produced the same fractional power
      law of 5/2 in all three MGs we investigated, suggesting a universal feature in
      MG.

PMID- 24856707
TI  - Fermi-surface reconstruction and complex phase equilibria in CaFe2As2.
AB  - Fermi-surface topology governs the relationship between magnetism and
      superconductivity in iron-based materials. Using low-temperature transport, angle
      resolved photoemission, and x-ray diffraction, we show unambiguous evidence of
      large Fermi-surface reconstruction in CaFe2As2 at magnetic spin-density-wave and
      nonmagnetic collapsed-tetragonal (cT) transitions. For the cT transition, the
      change in the Fermi-surface topology has a different character with no
      contribution from the hole part of the Fermi surface. In addition, the results
      suggest that the pressure effect in CaFe2As2 is mainly leading to a rigid-band
      like change of the valence electronic structure. We discuss these results and
      their implications for magnetism and superconductivity in this material.

PMID- 24856708
TI  - Merging of Landau levels in a strongly interacting two-dimensional electron
      system in silicon.
AB  - We show that the merging of the spin- and valley-split Landau levels at the
      chemical potential is an intrinsic property of a strongly interacting two
      dimensional electron system in silicon. Evidence for the level merging is given
      by available experimental data. 

PMID- 24856709
TI  - Real-space and reciprocal-space Berry phases in the Hall effect of Mn(1
      x)Fe(x)Si.
AB  - We report an experimental and computational study of the Hall effect in Mn(1
      x)Fe(x)Si, as complemented by measurements in Mn(1-x)Co(x)Si, when helimagnetic
      order is suppressed under substitutional doping. For small x the anomalous Hall
      effect (AHE) and the topological Hall effect (THE) change sign. Under larger
      doping the AHE remains small and consistent with the magnetization, while the THE
      grows by over a factor of 10. Both the sign and the magnitude of the AHE and the
      THE are in excellent agreement with calculations based on density functional
      theory. Our study provides the long-sought material-specific microscopic
      justification that, while the AHE is due to the reciprocal-space Berry curvature,
      the THE originates in real-space Berry phases.

PMID- 24856710
TI  - Extreme thermopower anisotropy and interchain transport in the quasi-one
      dimensional metal Li0.9Mo6O17.
AB  - Thermopower and electrical resistivity measurements transverse to the conducting
      chains of the quasi-one-dimensional metal Li0.9Mo6O17 are reported in the
      temperature range 5<=T<=500  K. For T>=400  K the interchain transport is
      determined by thermal excitation of charge carriers from a valence band ~0.14  eV
      below the Fermi level, giving rise to a large, p-type thermopower that coincides
      with a small, n-type thermopower along the chains. This dichotomy
      semiconductorlike in one direction and metallic in a mutually perpendicular
      direction-gives rise to substantial transverse thermoelectric effects and a
      transverse thermoelectric figure of merit among the largest known for a single
      compound.

PMID- 24856711
TI  - Electric-dipole-induced universality for Dirac fermions in graphene.
AB  - We study electric dipole effects for massive Dirac fermions in graphene and
      related materials. The dipole potential accommodates towers of infinitely many
      bound states exhibiting a universal Efimov-like scaling hierarchy. The dipole
      moment determines the number of towers, but there is always at least one tower.
      The corresponding eigenstates show a characteristic angular asymmetry, observable
      in tunnel spectroscopy. However, charge transport properties inferred from
      scattering states are highly isotropic. 

PMID- 24856712
TI  - Experimental observation of Dirac-like surface states and topological phase
      transition in Pb(1-x)Sn(x)Te(111) films.
AB  - The surface of a topological crystalline insulator (TCI) carries an even number
      of Dirac cones protected by crystalline symmetry. We epitaxially grew high
      quality Pb(1-x)Sn(x)Te(111) films and investigated the TCI phase by in situ angle
      resolved photoemission spectroscopy. Pb(1-x)Sn(x)Te(111) films undergo a
      topological phase transition from a trivial insulator to TCI via increasing the
      Sn/Pb ratio, accompanied by a crossover from n-type to p-type doping. In
      addition, a hybridization gap is opened in the surface states when the thickness
      of the film is reduced to the two-dimensional limit. The work demonstrates an
      approach to manipulating the topological properties of TCI, which is of
      importance for future fundamental research and applications based on TCI.

PMID- 24856713
TI  - Density-functional tight-binding simulations of curvature-controlled layer
      decoupling and band-gap tuning in bilayer MoS2.
AB  - Monolayer transition-metal dichalcogenides (TMDCs) display valley-selective
      circular dichroism due to the presence of time-reversal symmetry and the absence
      of inversion symmetry, making them promising candidates for valleytronics. In
      contrast, in bilayer TMDCs both symmetries are present and these desirable valley
      selective properties are lost. Here, by using density-functional tight-binding
      electronic structure simulations and revised periodic boundary conditions, we
      show that bending of bilayer MoS2 sheets breaks band degeneracies and localizes
      states on separate layers due to bending-induced strain gradients across the
      sheets. We propose a strategy for employing bending deformations in bilayer TMDCs
      as a simple yet effective means of dynamically and reversibly tuning their band
      gaps while simultaneously tuning valley-selective physics.

PMID- 24856714
TI  - Pure scaling operators at the integer quantum Hall plateau transition.
AB  - Stationary wave functions at the transition between plateaus of the integer
      quantum Hall effect are known to exhibit multifractal statistics. Here we explore
      this critical behavior for the case of scattering states of the Chalker
      Coddington network model with point contacts. We argue that moments formed from
      the wave amplitudes of critical scattering states decay as pure powers of the
      distance between the points of contact and observation. These moments in the
      continuum limit are proposed to be correlation functions of primary fields of an
      underlying conformal field theory. We check this proposal numerically by finite
      size scaling. We also verify the conformal field theory prediction for a three
      point function involving two primary fields. 

PMID- 24856715
TI  - High-Tc superconductivity near the anion height instability in Fe-based
      superconductors: analysis of LaFeAsO(1-x)H(x).
AB  - The isostructural transition in the tetragonal phase with a sizable change in the
      anion height, is realized in heavily H-doped LaFeAsO and (La,P) codoped CaFe2As2.
      In these compounds, the superconductivity with higher Tc (40-50 K) is realized
      near the isostructural transition. To find the origin of the anion-height
      instability and the role in realizing the higher-Tc state, we develop the orbital
      spin fluctuation theory by including the vertex correction. We analyze LaFeAsO(1
      x)H(x) and find that the non-nematic orbital fluctuations, which induce the anion
      height instability, are automatically obtained at x~0.5, in addition to the
      conventional nematic orbital fluctuations at x~0. The non-nematic orbital order
      triggers the isostructural transition, and its fluctuation would be a key
      ingredient to realize higher-Tc superconductivity of order 50 K.

PMID- 24856716
TI  - Spin-orbit-induced circulating currents in a semiconductor nanostructure.
AB  - Circulating orbital currents produced by the spin-orbit interaction for a single
      electron spin in a quantum dot are explicitly evaluated at zero magnetic field,
      along with their effect on the total magnetic moment (spin and orbital) of the
      electron spin. The currents are dominated by coherent superpositions of the
      conduction and valence envelope functions of the electronic state, are smoothly
      varying within the quantum dot, and are peaked roughly halfway between the dot
      center and edge. Thus the spatial structure of the spin contribution to the
      magnetic moment (which is peaked at the dot center) differs greatly from the
      spatial structure of the orbital contribution. Even when the spin and orbital
      magnetic moments cancel (for g=0) the spin can interact strongly with local
      magnetic fields, e.g., from other spins, which has implications for spin
      lifetimes and spin manipulation. 

PMID- 24856718
TI  - ac current generation in chiral magnetic insulators and Skyrmion motion induced
      by the spin Seebeck effect.
AB  - We show that a temperature gradient induces an ac electric current in
      multiferroic insulators when the sample is embedded in a circuit. We also show
      that a thermal gradient can be used to move magnetic Skyrmions in insulating
      chiral magnets: the induced magnon flow from the hot to the cold region drives
      the Skyrmions in the opposite direction via a magnonic spin transfer torque. Both
      results are combined to compute the effect of Skyrmion motion on the ac current
      generation and demonstrate that Skyrmions in insulators are a promising route for
      spin caloritronics applications. 

PMID- 24856717
TI  - Ferro-orbital ordering transition in iron telluride Fe(1+y)Te.
AB  - Fe(1+y)Te with y?0.05 exhibits a first-order phase transition on cooling to a
      state with a lowered structural symmetry, bicollinear antiferromagnetic order,
      and metallic conductivity, drho/dT>0. Here, we study samples with y=0.09(1),
      where the frustration effects of the interstitial Fe decouple different orders,
      leading to a sequence of transitions. While the lattice distortion is closely
      followed by incommensurate magnetic order, the development of bicollinear order
      and metallic electronic coherence is uniquely associated with a separate
      hysteretic first-order transition, at a markedly lower temperature, to a phase
      with dramatically enhanced bond-order wave (BOW) order. The BOW state suggests
      ferro-orbital ordering, where electronic delocalization in ferromagnetic zigzag
      chains decreases local spin and results in metallic transport.

PMID- 24856719
TI  - Classical antiferromagnetism in kinetically frustrated electronic models.
AB  - We study, by means of the density matrix renormalization group, the infinite U
      Hubbard model--with one hole doped away from half filling--in triangular and
      square lattices with frustrated hoppings, which invalidate Nagaoka's theorem. We
      find that these kinetically frustrated models have antiferromagnetic ground
      states with classical local magnetization in the thermodynamic limit. We identify
      the mechanism of this kinetic antiferromagnetism with the release of the kinetic
      energy frustration, as the hole moves in the established antiferromagnetic
      background. This release can occur in two different ways: by a nontrivial spin
      Berry phase acquired by the hole, or by the effective vanishing of the hopping
      amplitude along the frustrating loops.

PMID- 24856720
TI  - Optical characterization of electron-phonon interactions at the saddle point in
      graphene.
AB  - The role of many-body interactions is experimentally and theoretically
      investigated near the saddle point absorption peak of graphene. The time and
      energy-resolved differential optical transmission measurements reveal the
      dominant role played by electron-acoustic phonon coupling in band structure
      renormalization. Using a Born approximation for electron-phonon coupling and
      experimental estimates of the dynamic lattice temperature, we compute the
      differential transmission line shape. Comparing the numerical and experimental
      line shapes, we deduce the effective acoustic deformation potential to be
      Deff(ac)?5  eV. This value is in accord with recent theoretical predictions but
      differs from those extracted using electrical transport measurements.

PMID- 24856721
TI  - Electrically and mechanically tunable electron spins in silicon carbide color
      centers.
AB  - The electron spins of semiconductor defects can have complex interactions with
      their host, particularly in polar materials like SiC where electrical and
      mechanical variables are intertwined. By combining pulsed spin resonance with ab
      initio simulations, we show that spin-spin interactions in 4H-SiC neutral
      divacancies give rise to spin states with a strong Stark effect, sub-10(-6)
      strain sensitivity, and highly spin-dependent photoluminescence with intensity
      contrasts of 15%-36%. These results establish SiC color centers as compelling
      systems for sensing nanoscale electric and strain fields.

PMID- 24856722
TI  - Inversion symmetry breaking by oxygen octahedral rotations in the Ruddlesden
      Popper NaRTiO4 family.
AB  - Rotations of oxygen octahedra are ubiquitous, but they cannot break inversion
      symmetry in simple perovskites. However, in a layered oxide structure, this is
      possible, as we demonstrate here in A-site ordered Ruddlesden-Popper NaRTiO4 (R
      denotes rare-earth metal), previously believed to be centric. By revisiting this
      series via synchrotron x-ray diffraction, optical second-harmonic generation,
      piezoresponse force microscopy, and first-principles phonon calculations, we find
      that the low-temperature phase belongs to the acentric space group P42(1)m, which
      is piezoelectric and nonpolar. The mechanism underlying this large new family of
      acentric layered oxides is prevalent, and could lead to many more families of
      acentric oxides.

PMID- 24856723
TI  - Time- and angle-resolved photoemission spectroscopy of hydrated electrons near a
      liquid water surface.
AB  - We present time- and angle-resolved photoemission spectroscopy of trapped
      electrons near liquid surfaces. Photoemission from the ground state of a hydrated
      electron at 260 nm is found to be isotropic, while anisotropic photoemission is
      observed for the excited states of 1,4-diazabicyclo[2,2,2]octane and I- in
      aqueous solutions. Our results indicate that surface and subsurface species
      create hydrated electrons in the bulk side. No signature of a surface-bound
      electron has been observed.

PMID- 24856724
TI  - Eliminating friction with friction: 2D Janssen effect in a friction-driven
      system.
AB  - The Janssen effect is a unique property of confined granular materials
      experiencing gravitational compaction in which the pressure at the bottom
      saturates with an increasing filling height due to frictional interactions with
      side walls. In this Letter, we replace gravitational compaction with frictional
      compaction. We study friction-compacted 2D granular materials confined within
      fixed boundaries on a horizontal conveyor belt. We find that even with high
      friction side walls the Janssen effect completely vanishes. Our results
      demonstrate that gravity-compacted granular systems are inherently different from
      friction-compacted systems in at least one important way: vibrations induced by
      sliding friction with the driving surface relax away tangential forces on the
      walls. Remarkably, we find that the Janssen effect can be recovered by replacing
      the straight side walls with a sawtooth pattern. The mechanical force introduced
      by varying the sawtooth angle theta can be viewed as equivalent to a tunable
      friction force. By construction, this mechanical friction force cannot be relaxed
      away by vibrations in the system. 

PMID- 24856725
TI  - Measuring lipid membrane viscosity using rotational and translational probe
      diffusion.
AB  - The two-dimensional fluidity of lipid bilayers enables the motion of membrane
      bound macromolecules and is therefore crucial to biological function.
      Microrheological methods that measure fluid viscosity via the translational
      diffusion of tracer particles are challenging to apply and interpret for
      membranes, due to uncertainty about the local environment of the tracers. Here,
      we demonstrate a new technique in which determination of both the rotational and
      translational diffusion coefficients of membrane-linked particles enables
      quantification of viscosity, measurement of the effective radii of the tracers,
      and assessment of theoretical models of membrane hydrodynamics. Surprisingly, we
      find a wide distribution of effective tracer radii, presumably due to a variable
      number of lipids linked to each tracer particle. Furthermore, we show for the
      first time that a protein involved in generating membrane curvature, the vesicle
      trafficking protein Sar1p, dramatically increases membrane viscosity. Using the
      rheological method presented here, therefore, we are able to reveal a class of
      previously unknown couplings between protein activity and membrane mechanics. 

PMID- 24856726
TI  - Selective advantage of diffusing faster.
AB  - We study a stochastic spatial model of biological competition in which two
      species have the same birth and death rates, but different diffusion constants.
      In the absence of this difference, the model can be considered as an off-lattice
      version of the voter model and presents similar coarsening properties. We show
      that even a relative difference in diffusivity on the order of a few percent may
      lead to a strong bias in the coarsening process favoring the more agile species.
      We theoretically quantify this selective advantage and present analytical
      formulas for the average growth of the fastest species and its fixation
      probability. 

PMID- 24856727
TI  - Critical onset of layering in sedimenting suspensions of nanoparticles.
AB  - We quantitatively study the critical onset of layering in suspensions of
      nanoparticles in a solvent, where an initially homogeneous suspension, subject to
      an effective gravity a in a centrifuge, spontaneously forms well-defined layers
      of constant particle density, so that the density changes in a staircaselike
      manner along the axis of gravity. This phenomenon is well known; yet, it has
      never been quantitatively studied under reproducible conditions: therefore, its
      physical mechanism remained controversial and the role of thermal diffusion in
      this phenomenon was never explored. We demonstrate that the number of layers
      forming in the sample exhibits a critical scaling as a function of a; a critical
      dependence on sample height and transverse temperature gradient is established as
      well. We reproduce our experiments by theoretical calculations, which attribute
      the layering to a diffusion-limited convective instability, fully elucidating the
      physical mechanism of layering. 

PMID- 24856728
TI  - Glass transition accelerates the spreading of polar solvents on a soluble
      polymer.
AB  - We study the wetting of polymer layers by polar solvents. As previously observed,
      when a droplet of solvent spreads, both its contact angle and velocity decrease
      with time as a result of solvent transfers from the droplet to the substrate. We
      show that, when the polymer is initially glassy, the angle decreases steeply for
      a given value of the velocity, Ug. We demonstrate that those variations result
      from a plasticization, i.e., a glass transition, undergone by the polymer layer
      during spreading, owing to the increase of its solvent content. By analyzing
      previous predictions on the wetting of rigid and soft viscoelastic substrates, we
      relate Ug to the viscosity of the polymer gel close to the glass transition.
      Finally, we derive an analytical prediction for Ug based on existing predictions
      for the water transfer from the droplet to the substrate. Using polar solvents of
      different natures, we show that the experimental data compare well to the
      predicted expression for Ug.

PMID- 24856729
TI  - Impact of attractive interactions on the rheology of dense athermal particles.
AB  - Using numerical simulations, the rheological response of an athermal assembly of
      soft particles with tunable attractive interactions is studied in the vicinity of
      jamming. At small attractions, a fragile solid develops and a finite yield stress
      is measured. Moreover, the measured flow curves have unstable regimes, which lead
      to persistent shear banding. These features are rationalized by establishing a
      link between the rheology and the interparticle connectivity, which also provides
      a minimal model to describe the flow curves. 

PMID- 24856730
TI  - Direct mutagenesis of thousands of genomic targets using microarray-derived
      oligonucleotides.
AB  - Multiplex Automated Genome Engineering (MAGE) allows simultaneous mutagenesis of
      multiple target sites in bacterial genomes using short oligonucleotides. However,
      large-scale mutagenesis requires hundreds to thousands of unique oligos, which
      are costly to synthesize and impossible to scale-up by traditional
      phosphoramidite column-based approaches. Here, we describe a novel method to
      amplify oligos from microarray chips for direct use in MAGE to perturb thousands
      of genomic sites simultaneously. We demonstrated the feasibility of large-scale
      mutagenesis by inserting T7 promoters upstream of 2585 operons in E. coli using
      this method, which we call Microarray-Oligonucleotide (MO)-MAGE. The resulting
      mutant library was characterized by high-throughput sequencing to show that all
      attempted insertions were estimated to have occurred at an average frequency of
      0.02% per locus with 0.4 average insertions per cell. MO-MAGE enables cost
      effective large-scale targeted genome engineering that should be useful for a
      variety of applications in synthetic biology and metabolic engineering. 

PMID- 24856731
TI  - Bacteria and Toll-like receptor and cytokine mRNA expression profiles associated
      with canine arthritis.
AB  - The major forms of inflammatory canine arthritis are immune-mediated arthritis
      (IMA) and septic arthritis (SA), although some cases of cruciate disease (CD) are
      associated with significant levels of synovitis. In this study, the bacteria
      associated with canine arthritis were identified and mRNA expression levels of
      Toll-like receptors (TLRs) and pro-inflammatory cytokines determined. Of the 40
      synovial fluid samples analysed, bacteria were isolated from 12 samples by
      culture (2 CD, 10 SA) and detected in 4 samples (3 CD, 1 SA) using culture
      independent methods. Statistically significant increases in TLR2, tumour necrosis
      factor-alpha (TNF-alpha), interleukin-6 (IL-6) and IL-12 mRNA expression were
      seen in all disease groups compared to normal controls. All disease groups had
      decreased mRNA expression of other TLRs compared to normal controls, but this did
      not reach statistical significance. Synovial fluid cell counts revealed that the
      highest number and proportion of mononuclear cells and neutrophils were found in
      the IMA and SA samples, respectively. Age had an effect on the TLR and cytokine
      mRNA expression profiles: TNF-alpha (p=0.043) and IL-12 (p=0.025) mRNA expression
      was increased and TLR4 mRNA expression was reduced (p=0.033) in dogs up to 4
      years of age compared to older animals. In the 10 SA samples from which bacteria
      were isolated, statistically significant increases in TLR2, TLR7, TNF-alpha and
      IL-6 mRNA expression were observed. It is concluded that canine arthritis is
      associated with increased mRNA levels of pro-inflammatory cytokines, which could
      in some cases be mediated by bacteria through activation of TLR2. 

PMID- 24856732
TI  - Identification of potential biomarkers of disease progression in bovine
      tuberculosis.
AB  - Bovine tuberculosis (bTB) remains an important animal and zoonotic disease in
      many countries. The diagnosis of bTB is based on tuberculin skin test and IFN
      gamma release assays (IGRA). Positive animals are separated from the herd and
      sacrificed. The cost of this procedure is difficult to afford for developing
      countries with high prevalence of bTB; therefore, the improvement of diagnostic
      methods and the identification of animals in different stages of the disease will
      be helpful to control the infection. To identify biomarkers that can discriminate
      between tuberculin positive cattle with and without tuberculosis lesions (ML+ and
      ML-, respectively), we assessed a group of immunological parameters with three
      different classification methods: lineal discriminant analysis (LDA), quadratic
      discriminant analysis (QDA) and K nearest neighbors (k-nn). For this purpose, we
      used data from 30 experimentally infected cattle. All the classifiers (LDA, QDA
      and k-nn) selected IL-2 and IL-17 as the most discriminatory variables. The best
      classification method was LDA using IL-17 and IL-2 as predictors. The addition of
      IL-10 to LDA improves the performance of the classifier to discriminate ML
      individuals (93.3% vs. 86.7%). Thus, the expression of IL-17, IL-2 and, in some
      cases, IL-10 would serve as an additional tool to study disease progression in
      herds with a history of bTB. 

PMID- 24856733
TI  - Fundamental relation between molecular geometry and real-space topology. Combined
      AIM, ELI-D, and ASF analysis of hapticities and intramolecular hydrogen-hydrogen
      bonds in zincocene-related compounds.
AB  - Despite numerous advanced and widely distributed bonding theories such as MO, VB,
      NBO, AIM, and ELF/ELI-D, complex modes of bonding such as M-Cp*((R)) interactions
      (hapticities) in asymmetrical metallocenes or weak intramolecular interactions
      (e.g., hydrogen-hydrogen (H...H) bonds) still remain a challenge for these
      theories in terms of defining whether or not an atom-atom interaction line (a
      "chemical bond") should be drawn. In this work the intramolecular Zn-C(Cp*(R)) (R
      = Me, -(CH2)2NMe2, and -(CH2)3NMe2) and H...H connectivity of a systematic set of
      12 zincocene-related compounds is analyzed in terms of AIM and ELI-D topology
      combined with the recently introduced aspherical stockholder fragment (ASF)
      surfaces. This computational analysis unravels a distinct dependency of the AIM
      and ELI-D topology against the molecular geometry for both types of interactions,
      which confirms and extends earlier findings on smaller sets of compounds.
      According to these results the complete real-space topology including strong,
      medium, and weak interactions of very large compounds such as proteins may be
      reliably predicted by sole inspection of accurately determined molecular
      geometries, which would on the one hand afford new applications (e.g., accurate
      estimation of numbers, types, and strengths of intra- and intermolecular
      interactions) and on the other hand have deep implications on the significance of
      the method.

PMID- 24856734
TI  - Epidemiologic profile of women presenting to the National Hospital of Niamey,
      Niger for vaginal fistula repair.
AB  - OBJECTIVE: To describe the epidemiologic profile of women with vaginal fistulas
      presenting to the surgical mission trips of the International Organization for
      Women and Development (IOWD) at the National Hospital of Niamey, Niger. METHODS:
      In a cross-sectional retrospective study, data were assessed from a database of
      women who attended the IOWD at the National Hospital of Niamey, Niger, from
      October 2003 to April 2009. The database was compiled from the history and
      physical examination forms for each patient visit. RESULTS: During the study
      period, there were 1323 data entries and 896 initial patient visits. Overall, 580
      women presented with obstetric fistulas. The median age was 29 years; the mean
      age at marriage was 16 years; 73.7% were married. The median age at first
      delivery was 18 years; the mean number of past full-term pregnancies was 3; the
      mean parity was 4. Vaginal (66.3%) or cesarean (27.7%) delivery was a common
      predisposing factor for developing an obstetric fistula. Overall, 97.4% of women
      labored for 24 hours or more; 75.4% delivered in hospital; 82.9% had a
      stillbirth. CONCLUSION: Women presenting to the IOWD for fistula repair have
      specific epidemiologic characteristics. Better understanding of these
      characteristics might help to formulate future public health programs for fistula
      prevention.

PMID- 24856736
TI  - Bacteremia prediction model using a common clinical test in patients with
      community-acquired pneumonia.
AB  - PURPOSE: The aim of this study was to construct a bacteremia prediction model
      using commonly available clinical variables in hospitalized patients with
      community-acquired pneumonia (CAP). BASIC PROCEDURES: A prospective database
      including patients who were diagnosed with CAP in the emergency department was
      analyzed. Independent risk factors were investigated by using multivariable
      analysis in 60% of the cohort. We assigned a weighted value to predictive factor
      and made a prediction rule. This model was validated both internally and
      externally with the remaining 40% of the cohort and a cohort from an independent
      hospital. The low-risk group for bacteremia was defined as patients who have a
      risk of bacteremia less than 3%. MAIN FINDINGS: A total of 2422 patients were
      included in this study. The overall rate of bacteremia was 5.7% in the cohort.
      The significant factors for predicting bacteremia were the following 7 variables:
      systolic blood pressure less than 90 mm Hg, heart rate greater than 125 beats per
      minute, body temperature less than 35  degrees C or greater than 40  degrees C,
      white blood cell less than 4000 or 12,000 cells per microliter, platelets less
      than 130,000 cells per microliter, albumin less than 3.3 g/dL, and C-reactive
      protein greater than 17 mg/dL. After using our prediction rule for the validation
      cohorts, 78.7% and 74.8% of the internal and external validation cohorts were
      classified as low-risk bacteremia groups. The areas under the receiver operating
      characteristic curves were 0.75 and 0.79 for the internal and external validation
      cohorts. PRINCIPAL CONCLUSIONS: This model could provide guidelines for whether
      to perform blood cultures for hospitalized CAP patients with the goal of reducing
      the number of blood cultures.

PMID- 24856737
TI  - In-hospital cardiac arrest: characteristics and outcome after implementation of
      systematic practice-oriented training.
AB  - Survival after in-hospital cardiac arrest (CA) has been reported to be
      surprisingly low without any major improvement during the last decade.
      Cardiopulmonary resuscitation (CPR) quality affects survival after CA, and
      specific education is necessary for health care professionals participating in
      CPR. Decisions regarding CPR and do not attempt resuscitation (DNAR) orders
      remain demanding, as does including patients in the process. Addressed training
      regarding CPR/DNAR orders is necessary to improve the CPR/DNAR decision process
      used by physicians. The aim of this retrospective study is to evaluate the
      clinical impact (return of spontaneous circulation and 21-day survival after CA)
      of an intervention within one single hospital, including a systematic education
      of all health care professionals in CPR. In total, there were 33 in-hospital CAs
      before (12 months) and 176 after (36 months) the intervention. No significant
      difference was found between the 2 calendar periods. 

PMID- 24856738
TI  - Evidence-based diagnosis and thrombolytic treatment of cardiac arrest or
      periarrest due to suspected pulmonary embolism.
AB  - When a previously healthy adult experiences atraumatic cardiac arrest, providers
      must quickly identify the etiology and implement potentially lifesaving
      interventions such as advanced cardiac life support. A subset of these patients
      develop cardiac arrest or periarrest due to pulmonary embolism (PE). For these
      patients, an early, presumptive diagnosis of PE is critical in this patient
      population because administration of thrombolytic therapy may significantly
      improve outcomes. This article reviews thrombolysis as a potential treatment
      option for patients in cardiac arrest or periarrest due to presumed PE,
      identifies features associated with a high incidence of PE, evaluates
      thrombolytic agents, and systemically reviews trials evaluating thrombolytics in
      cardiac arrest or periarrest. Despite potentially improved outcomes with
      thrombolytic therapy, this intervention is not without risks. Patients exposed to
      thrombolytics may experience major bleeding events, with the most devastating
      complication usually being intracranial hemorrhage. To optimize the risk-benefit
      ratio of thrombolytics for treatment of cardiac arrest due to PE, the clinician
      must correctly identify patients with a high likelihood of PE and must also
      select an appropriate thrombolytic agent and dosing protocol. 

PMID- 24856739
TI  - Bleeding complications of central venous catheterization in septic patients with
      abnormal hemostasis.
AB  - OBJECTIVES: Central venous catheterization (CVC) is thought to be relatively
      contraindicated in patients with thrombocytopenia or coagulopathy. We measured
      the 24-hour incidence of bleeding in septic emergency department (ED) patients
      undergoing CVC. METHODS: This multicenter, retrospective cohort study included
      septic ED patients undergoing CVC with one of the following: platelets less than
      100,000/MUL, international normalized ratio at least 1.3, or partial
      thromboplastin time at least 35 seconds. Major bleeding included radiographically
      confirmed intrathoracic, mediastinal, or internal neck hemorrhage or line-related
      bleeding causing hemodynamic compromise. Minor bleeding included local oozing or
      superficial hematoma. Multivariable regression analysis was performed to
      determine the association between candidate variables and hemorrhagic
      complications. RESULTS: Of the 936 cases, mean age was 68.1 years; 535 (57.2%)
      were male. Two or more qualifying laboratory abnormalities were present in 204
      cases (21.8%). The proceduralists were predominately attendings (790; 84.4%). The
      initial veins were the internal jugular (n = 800; 85.5%), subclavian (n = 123;
      13.1%), and femoral (n = 13; 1.4%). Initial access was successful in 872 cases
      (93.2%). We found one case (95% upper confidence limit: 0.6%) of major bleeding
      and 37 cases (4.0%; 95% confidence interval [CI], 2.8%-5.4%) of minor bleeding.
      Only failed access at the initial site was independently associated with
      hemorrhagic outcomes: adjusted odds ratio 8.2 (95% CI, 3.7-18.0). CONCLUSIONS:
      Major bleeding from CVC in ED patients with abnormal hemostasis is rare. Minor
      bleeding is uncommon and infrequently requires intervention. Successful
      catheterization on the initial attempt is associated with fewer hemorrhagic
      complications. These results can inform the risk/benefit calculus for CVC in this
      population.

PMID- 24856740
TI  - Stress-induced cardiomyopathy in pheochromocytoma: the way we treat and the way
      we think.

PMID- 24856741
TI  - Pitfalls in the ultrasound diagnosis of pneumothorax: the authors respond.

PMID- 24856742
TI  - Body mass index as a prognostic factor in organophosphate-poisoned patients.
AB  - Organophosphate poisoning is a serious clinical entity and considerable morbidity
      and mortality. Several factors have been identified to predict outcomes of
      organophosphate poisoning. Organophosphates are lipophilic and therefore
      predicted to have a large volume of distribution and to rapidly distribute into
      tissue and fat. Thus, toxic effects of organophosphate would be expected to last
      longer in obese patients. We investigated the relationship between obesity and
      clinical course in 112 acute organophosphate-poisoned patients from an initial
      medical record review of 234 patients. One hundred twenty-two patients were
      excluded: 6 were children, 14 had an uncertain history of exposure and of
      uncertain agent, 10 were transferred to another hospital, 67 were discharged from
      the emergency department because their toxicity was mild, 21 had carbamate
      poisoning, and 4 did not have height or weight checked. Clinical features, body
      mass index, Glasgow Coma Scale, laboratory findings, serum cholinesterase
      activity, electrocardiogram finding, management, and outcomes were examined. The
      lipid solubility of the implicated organophosphate was characterized by its
      octanol/water coefficient. Forty of 112 patients were obese. Obese patients who
      were poisoned by high lipophilicity organophosphate compounds had a need for
      longer use of mechanical ventilation, intensive care unit care, and total length
      of admission. Body mass index can provide a guide to physicians in predicting
      clinical course and management in organophosphate-poisoned patients. 

PMID- 24856743
TI  - Redefinition of diagnostic role of inferior vena cava ultrasonography in the
      identification of acute heart failure.

PMID- 24856744
TI  - Human immunodeficiency virus testing pitfalls and clinical suspicion.
AB  - Universal human immunodeficiency virus (HIV) screening was recommended in 2012,
      and major improvements in HIV testing have occurred in the past decade, but
      identification of HIV infected individuals remains inadequate in the United
      States. We report the case of a seronegative HIV-infected man who despite
      clinical and laboratory findings of acquired immunodeficiency syndrome,repeatedly
      tested nonreactive to third-generation HIV enzyme immunoassays (EIAs) and Western
      blot testing. Serologic diagnosis in this case required fourth-generation EIA
      testing due to the seronegativity of standard testing. The fourth-generation HIV
      EIA was positive presumably because it detects p24 HIV antigen as well as
      antibodies, unlike rapid HIV tests and third-generation HIV EIAs.This case
      highlights not only the importance of frontline providers to understand the
      different testing methodologies for HIV screening and their limitations but the
      importance of clinical suspicion as well.

PMID- 24856745
TI  - Computed tomography is not justified in every pediatric blunt trauma patient with
      a suspicious mechanism of injury.
AB  - OBJECTIVE: Computed tomography (CT) has become an important tool for the
      diagnosis of intra-abdominal and chest injuries in patients with blunt trauma.
      The role of CT in conscious asymptomatic patients with a suspicious mechanism of
      injury remains controversial. This controversy intensifies in the management of
      pediatric blunt trauma patients, who are much more susceptible to radiation
      exposure. The objective of this study was to evaluate the role of abdominal and
      chest CT imaging in asymptomatic pediatric patients with a suspicious mechanism
      of injury. METHODS: Forty-two pediatric patients up to 15 years old were
      prospectively enrolled. All patients presented with a suspicious mechanism of
      blunt trauma and multisystem injury. They were neurologically intact and had no
      signs of injury to the abdomen or chest. Patients underwent CT imaging of the
      chest and abdomen as part of the initial evaluation. RESULTS: Thirty-one patients
      (74%) had a normal CT scan. Two patients of 11 with an abnormal CT scan required
      a change in management and were referred for observation in the Intensive Care
      Unit. None of the patients required surgical intervention. CONCLUSION: The
      routine use of CT in asymptomatic pediatric patients with a suspicious mechanism
      of blunt trauma injury is not justified.

PMID- 24856746
TI  - Subcutaneous hematoma under tension: a bedside intervention.

PMID- 24856747
TI  - Naproxen-induced methemoglobinemia in an alcohol-dependent patient.
AB  - The authors report a case of acute methemoglobinemia in a patient treated with
      naproxen for the common cold. A 42-year-old Asian woman began taking naproxen
      sodium and methocarbamol formylagia, chills, and coughing. On the day prior to
      her emergency department (ED) admission,the patient was taking lorazepam,
      trazodon, and paroxetine in addition to the naproxen and methocarbamol prescribed
      for the cold symptoms, and she also ingested approximately 300 mL of 20% alcohol.
      Upon awakening the next morning, the patient experienced dyspnea and dizziness.
      At the hospital, she was diagnosed with severe methemoglobinemia. After
      initiation of methylene blue therapy, the patient's symptoms improved
      substantially and her serum methemoglobin levels decreased. After 10 days in the
      hospital, the patient was discharged without any complications.Naproxen is known
      to cause oxidative stress. Alcohol is known to reduce G6PD activity, and thus it
      is hypothesized that the administration of naproxen in an alcohol-dependent
      patient caused methemoglobinemia.

PMID- 24856748
TI  - Randomized trial of tourniquet vs blood pressure cuff for target vein dilation in
      ultrasound-guided peripheral intravenous access.
AB  - BACKGROUND: Ten percent of the time, peripheral intravenous access (PIV) is not
      obtained in 2 attempts in the emergency department. Typically, a tourniquet is
      used to dilate the target vein; but recent research showed that a blood pressure
      (BP) cuff improves dilation, which may translate to increased PIV success.
      OBJECTIVES: We sought to determine if there is improved success in obtaining
      ultrasound-guided PIV using a BP cuff vs a tourniquet in "difficult stick"
      patients. METHODS: This is a prospective, randomized, single-blinded trial. Adult
      patients requiring PIV with at least 2 prior failed attempts were enrolled.
      Patients were assigned to tourniquet or BP cuff for target vein dilation
      randomly. Nurses prepared the patient for PIV attempt by either placing a BP cuff
      inflated to 150 mm Hg or placing a tourniquet on the chosen extremity. The
      extremity was draped to blind the physician to assignment. Physicians then
      attempted ultrasound-guided PIV. Failures were defined as IVs requiring greater
      than 3 ultrasound-guided attempts or 30 minutes, or patient intolerance. If
      failure occurred, the physician was unblinded; and the patient could be crossed
      over and reattempted. RESULTS: Thirty-eight patients were enrolled. The success
      rate for the tourniquet group (n = 17) and BP cuff group (n = 21) was 82.4% and
      47.6%, respectively (P = .04). There were no differences between groups for
      vessel depth, diameter, or procedure time. Six in the BP cuff group were crossed
      over and had successful PIV obtained with tourniquet. CONCLUSIONS: Tourniquet is
      superior to BP cuff for target vein dilation in ultrasound-guided PIV.

PMID- 24856749
TI  - ST-segment elevation after direct current shock mimicking acute myocardial
      infarction: a case report and review of the literature.
AB  - External direct current (DC) shocks are and have long been commonly used for
      electrical cardioversion/defibrillation of atrial or ventricular arrhythmias. ST
      segment elevation after cardio version with DC is an easily ignored phenomenon,
      occurring acutely and resolving during the first few minutes postshock. Here, we
      describe electrocardiographic findings of widespread ST-segment elevation lasting
      at least 1 hour after DC cardioversion for ventricular defibrillation due to
      Brugada syndrome and mimicking acute myocardial infarction (AMI). This case of ST
      segment elevation without a dynamic and evolving AMI underscores the need to
      consider other causes of ST-segment elevation.

PMID- 24856750
TI  - Cerebral oximetry with blood volume index in asystolic pediatric cerebrospinal
      fluid malfunctioning shunt patients.
AB  - Pediatric cerebrospinal fluid shunt malfunctions can present with varying
      complaints. The primary cause is elevated intracranial pressure (ICP).
      Malfunctioning sites are the proximal or distal sites[1-4]. A rare presenting
      complaint is cardiac arrest. Immediate ICP reduction is the only reversible
      option for this type of cardiac arrest.

PMID- 24856751
TI  - Diagnosing frontal lobe epilepsy in the ED.
AB  - Frontal lobe seizures are a common form of epilepsy. It has a variable
      presentation and can often be missed in the emergency department (ED). Missing
      this diagnosis can lead to a delay in treatment and poor outcome for cognitive
      function. We hereby present a case of a 14-year-old girl who presented to our ED
      after the development of abnormal movements. Knowledge of the anatomy behind the
      development of partial seizures and the best testing modality can aid in the
      diagnosis. In this review, we attempt to discuss the pathophysiology of frontal
      lobe epilepsy and what physical examination findings and testing will best lead
      to a diagnosis.

PMID- 24856752
TI  - Acute pediatric stroke-what's the hurry? A case for emergency physician-performed
      echocardiography.
AB  - Acute ischemic stroke in a pediatric population is uncommon and has a different
      etiology from the adult population. We describe a case of acute ischemic stroke
      for which emergent, physician-sonographer-performed transthoracic
      echocardiography (TTE) changed his outcome.The patient in this case presented
      with left-sided hemiparesis,with subsequent CT Angiography (CTA) imaging and
      follow-on neurosurgical embolectomy for a proximal middle cerebral artery
      occlusion after which showed early recovery of muscular deficit. The cause
      ultimately was from an atrialmyxoma that was identified early by emergency
      physician-performed TTE and led to early resection possibly preventing recurrence
      of stroke.

PMID- 24856753
TI  - Myocarditis with normal left ventricular function and troponin of 266.
AB  - We are reporting a case, which may represent a new entity within the diagnosis of
      acute myocarditis. The patient was admitted with new onset atrioventricular
      block, very high troponin I, peaking at 266ng/mL, and normal left ventricular
      function. We also used a novel computer tomography technique with delayed
      enhancement to diagnose myocarditis, as the patient with a permanent pacemaker
      could not have magnetic resonance imaging.

PMID- 24856755
TI  - Yang-tonifying traditional Chinese medicinal plants and their potential
      phytoandrogenic activity.
AB  - The concept of phytoandrogens, plants that contain androgens or those that
      stimulate androgenic activity in men, is relatively new. In traditional Chinese
      medicine a number of phytoandrogens are classified in medicinal plant
      restoratives for reinforcing yang, and they find their application in the
      treatment of the kidney yang deficiency diseases. In this review, the
      phytoandrogens used in traditional Chinese medicine are listed, and their proven
      applications in the treatment of kidney yang deficiency diseases, such as sexual
      disorders, cancer, and obesity and associated metabolic syndromes are presented.
      As a background, the mechanism of action of androgens, their synthesis and
      metabolism, the interrelations of androgens and estrogens, as well as the state
      of art methods to detect and analyze these hormonal activities in medicinal
      plants are discussed. 

PMID- 24856756
TI  - Indigenous plant medicines for health care: treatment of Diabetes mellitus and
      hyperlipidemia.
AB  - Medicinal plants have played an important role in treating and preventing a
      variety of diseases throughout the world. Metabolic syndrome had become a global
      epidemic, defined as a cluster of three of five criteria: insulin resistance and
      glucose intolerance, abdominal obesity, hypertension, low high-density
      cholesterol, and hypertriglyceridemia. The current review focuses on Indian
      medicinal plant drugs and plants used in the treatment of diabetes and
      hyperlipidemia. Though there are various approaches to reduce the ill-effects of
      diabetes and hyperlipidemia and its secondary complications, plant-based drugs
      are preferred due to lesser side effects and low cost. The current review focuses
      on twenty-three medicinal plants used in the treatment of Diabetes mellitus and
      nine medicinal plants used in the treatment of hyperlipidemia. The wealth of
      knowledge on medicinal plants points to a great potential for research and the
      discovery of new drugs to fight diseases, including diabetes and hyperlipidemia. 

PMID- 24856757
TI  - Cardioprotective and antioxidant effects of oleogum resin "Olibanum" from Bos
      Boswellia carteri Birdw. (Bursearceae).
AB  - One of the leading causes of death worldwide is cardiovascular disease, hence
      searching for a cure is an important endeavor. The totally safe, edible, and
      inexpensive Boswellia plant exudate, known as olibanum or frankincense, is
      considered to possess diverse medicinal values in traditional medicine and from
      recent biological studies. Investigating the cardioprotective and antioxidant
      activities of olibanum from a Boswellia species, family Bursearaceae, namely
      Boswellia carteri Birdw. was the aim of this study. Cardioprotective activity was
      evaluated using a model of myocardial infarction induced by isoprenaline (ISO),
      while antioxidant activity was tested adopting nitric oxide scavenging (NOS) and
      azino-bis-3-ethyl benzthiazoline-6-sulfonic acid (ABTS) assays. The results
      revealed a mild cardioprotective effect and weak antioxidant activity.

PMID- 24856758
TI  - Modified Si-Miao-San ameliorates pancreatic B cell dysfunction by inhibition of
      reactive oxygen species-associated inflammation through AMP-kinase activation.
AB  - AIM: To observe the effect of modified Si-Miao-San (mSMS) on advanced glycation
      end products (AGEs)-induced pancreatic B cell dysfunction, as well as examining
      the underlying mechanisms. METHOD: Pancreatic B cells (INS-1) were stimulated
      with advanced glycation end products (AGEs, 200 MUg.mL(-1)) for 24 h to produce
      dysfunction in pancreatic B cells and the effects of mSMS observed on insulin
      secretion, NF-kappaB (p65) phosphorylation, reactive oxygen species (ROS)
      production, mitochondria membrane potential (Deltapsim), cell apoptosis,
      phosphorylation of AMP-kinase (AMPK), and caspase 3 activity. RESULTS: The AGEs
      challenge resulted in increased basal insulin secretion, but decreased insulin
      secretion in response to high glucose, whereas this situation was reversed by
      mSMS treatment. AGEs stimulation induced NF-kappaB (p65) phosphorylation and
      reactive oxygen species (ROS) production, as well as Deltapsim collapse and cell
      apoptosis. mSMS inhibited ROS production and inhibited NF-kappaB activation by
      attenuating p65 phosphorylation. Meanwhile, AGEs-induced Deltapsim collapse and
      cell apoptosis were also reversed by mSMS treatment. Compound C, an inhibitor of
      AMP-Kinase (AMPK), abolished the beneficial effects of mSMS on the regulation of
      B cell function, indicating the involvement of AMPK. CONCLUSION: mSMS ameliorated
      AGEs-induced B cell dysfunction by suppressing ROS-associated inflammation, and
      this action was related to its beneficial regulation of AMPK activity.

PMID- 24856759
TI  - Ma Huang Tang ameliorates asthma though modulation of Th1/Th2 cytokines and
      inhibition of Th17 cells in ovalbumin-sensitized mice.
AB  - AIM: Ma Huang Tang (Ephedra decoction, MHT) is a famous classical formula from
      Shang Han Lun by Zhang Zhongjing in the Han Dynasty. The anti-asthmatic effects
      of MHT and the possible mechanisms were tested. METHOD: An asthma model was
      established by ovalbumin (OVA)-induction in mice. A total of forty-eight mice
      were randomly assigned to six experimental groups: control, model, dexamethasone
      (2 mg.kg(-1)) and MHT (5, 10, and 20 mg.kg(-1)). Airway resistance (Raw) was
      measured by the forced oscillation technique, histological studies were evaluated
      by hematoxylin and eosin (HE) staining, Th1/Th2 and Th17 cytokines were evaluated
      by enzyme-linked immunosorbent assay (ELISA), and Th17 cells were evaluated by
      flow cytometry (FCM). RESULTS: This study demonstrated that MHT inhibited OVA
      induced increases in Raw and eosinophil count; interleukin (IL)-4 and IL-17
      levels were recovered in bronchoalveolar lavage fluid, increased IFN-gamma level
      in bronchoalveolar lavage fluid. Histological studies demonstrated that MHT
      substantially inhibited OVA-induced eosinophilia in lung tissue. Flow cytometry
      studies demonstrated that MHT substantially inhibited Th17 cells. CONCLUSION:
      These findings suggest that MHT may effectively ameliorate the progression of
      asthma, and could be further investigated for potential use as a therapy for
      patients with allergic asthma.

PMID- 24856760
TI  - Effects of feeding tyrosine and phenylalanine on the accumulation of
      phenylethanoid glycosides to Cistanche deserticola cell suspension culture.
AB  - AIM: To investigate the effects of feeding phenylalanine (Phe) and tyrosine (Tyr)
      on the accumulation of total phenolic compounds and four phenylethanoid
      glycosides (PeGs) to a cell suspension culture of the parasitic plant Cistanche
      deserticola. METHOD: A cell suspension culture of C. deserticola was established
      and precursors of different concentrations were fed. In each group, the cell was
      sampled at the 24(th) day after inoculation. The content of total phenolic
      compounds and four PeGs compounds were determined using the Folin-Ciocalteu
      method and an HPLC method, respectively. RESULTS: In the Phe fed cells, the
      maximum PeGs yield was achieved when Phe was fed at 1.5 mmol.L(-1) and the yield
      reached 1.13 times the control cell concentration. In the Tyr fed cells, the
      maximum yield of PeGs was 1.60 times of control when 0.75 mmol.L(-1) Tyr was fed
      to the cells. Furthermore, it was found that the salidroside yield was 4.01 times
      of control group when 5 mmol.L(-1) Tyr was fed. CONCLUSION: Tyr is a better
      precursor for PeGs accumulation compared with Phe, and the rate limiting enzymes
      might be involved in the Tyr branch.

PMID- 24856761
TI  - A new Lycopodium alkaloid from Phlegmariurus fargesii.
AB  - AIM: To investigate the chemical constituents from the whole plants of
      Phlegmariurus fargesii. METHOD: Compounds were isolated by repeated silica gel
      column chromatography. Their structures were elucidated by spectroscopic methods
      and chemical correlation. The acetylcholinesterase (AChE) inhibitory activity of
      the isolated compounds was evaluated. RESULTS: A new Lycopodium alkaloid,
      lycopodine N-oxide (1), along with lycopodine (2), 8,15-dehydrolycopodine (3),
      6alpha-hydroxylycopodine (4), deacetyllycoclavine (5), N-methylhuperzine B (6),
      lycodine (7), and phlegmarine (8), was isolated. CONCLUSION: Compound 1 is a new
      Lycopodium alkaloid, and compound 3 was obtained from nature for the first time.
      Other alkaloids are isolated from this plant for the first time.

PMID- 24856762
TI  - A new flavonol C-glycoside and a rare bioactive lignanamide from Piper wallichii
      Miq. Hand.-Mazz.
AB  - This study was conducted to investigate the chemical constituents of Piper
      wallichii (Miq.) Hand.-Mazz. and evaluate their biological activity. Compounds
      were isolated by various column chromatographic methods, and their structures
      were elucidated on the basis of physical characteristics and spectral data. The
      1, 1-diphenyl-2-picrylhydrazyl (DPPH)-scavenging activity and
      acetylcholinesterase (AChE)-inhibitory activity of the compounds were evaluated.
      Five compounds were obtained and identified as 8-C-beta-D
      glucopyranosylkaempferol-3-O-beta-D-glucopyranoside (1), 1, 2-dihydro-6,8
      dimethoxy-7-hydroxy-1-(3, 5-dimethoxy-4-hydroxyphenyl)-N(1), N(2)-bis-[2-(4
      hydroxyphenyl)ethyl]-2, 3-naphthalene dicarboxamide (2), goniothalactam (3),
      aristololactam A IIIa (4) and piperlonguminine (5). Compound 1 was a new flavonol
      C-glycoside, 2 was a rare lignanamide, which was isolated from the family
      Piperaceae for the first time, and compound 3 was isolated from this plant for
      the first time. Among them, 2 showed potent DPPH-scavenging activity, with IC50
      of 31.38 +/- 0.97 MUmol.L(-1); Compounds 2, 3, and 4 showed AChE inhibitory
      activity at 100 MUmol.L(-1), with inhibition rates of 28.57% +/- 1.47%, 18.48% +/
      2.41% and 17.4% +/- 3.03%, respectively.

PMID- 24856763
TI  - Preparation and quality assessment of high-purity ginseng total saponins by ion
      exchange resin combined with macroporous adsorption resin separation.
AB  - AIM: To prepare high-purity ginseng total saponins from a water decoction of
      Chinese ginseng root. METHOD: Total saponins were efficiently purified by dynamic
      anion-cation exchange following the removal of hydrophilic impurities by
      macroporous resin D101. For quality control, ultrahigh-performance liquid
      chromatography with a charged aerosol detector (CAD) was applied to quantify
      marker components. The total saponin content was estimated by a colorimetric
      method using a vanillin-vitriol system and CAD response. RESULTS: D201, which
      consisted of a cross-linked polystyrene matrix and -N(+)(CH3)3 functional groups,
      was the best of the four anion exchange resins tested. However, no significant
      difference in cation exchange ability was observed between D001 (strong acid) and
      D113 (weak acid), although they have different functional groups and matrices.
      After purification in combination with D101, D201, and D113, the estimated
      contents of total saponins were 107% and 90% according to the colorimetric method
      and CAD response, respectively. The total amount of representative ginsenosides
      Re, Rd, Rg1, and compound K was approximately 22% based on ultrahigh-performance
      liquid chromatography-CAD quantitative analysis. CONCLUSION: These findings
      suggest that an ion exchange resin, combined with macroporous adsorption resin
      separation, is a promising and feasible purification procedure for neutral
      natural polar components.

PMID- 24856764
TI  - Study of the anti-MRSA activity of Rhizoma coptidis by chemical fingerprinting
      and broth microdilution methods.
AB  - AIM: Methicillin-resistant Staphylococcus aureus (MRSA) is a pathogenic bacterium
      that causes both hospital- and community-acquired infections, and for which
      single-drug treatments are becoming less efficient. Rhizoma coptidis has been
      used for more than two thousand years in China to treat diarrhea, fever, and
      jaundice. In this study, the anti-MRSA activity of Rhizoma coptidis is examined
      and its effective components sought. METHODS: The mecA and norA genes were
      determined by PCR amplification and sequencing. Drug susceptibility of
      Staphylococcus aureus ATCC43300 was performed using the VITEK2 compact system.
      The chemical fingerprint of Rhizoma coptidis was investigated using HPLC and
      preparative liquid chromatography, and the anti-MRSA activity was determined
      using an improved broth microdilution method. RESULTS: The drug susceptibility
      test revealed that the penicillin-binding protein phenotype of the strain changed
      in comparison to penicillin-sensitive Staphylococcus aureus. Ten batches of
      Rhizoma coptidis showed anti-MRSA activity on the norA-negative Staphylococcus
      aureus strain, as well as the strain that contained a norA gene. The spectrum
      effect relationship revealed that the berberine alkaloids were the effective
      components, within which berberine, coptisine, palmatine, epiberberine, and
      jatrorrhizine were the major components. CONCLUSION: This study lays a foundation
      for in vivo studies of Rhizoma coptidis and for the development of multi
      component drugs.

PMID- 24856765
TI  - Increased incidence of postoperative stiffness after arthroscopic compared with
      open biceps tenodesis.
AB  - PURPOSE: To determine the incidence of postoperative stiffness after open and
      arthroscopic biceps tenodesis, compare the incidence between each method, and
      determine relevant risk factors for its occurrence. METHODS: A consecutive series
      of patients who underwent biceps tenodesis during a 3-year period were
      retrospectively reviewed. RESULTS: We evaluated 249 patients, which included 143
      who underwent open subpectoral tenodesis and 106 who underwent arthroscopic
      suprapectoral tenodesis. The mean overall follow-up period for the arthroscopic
      group was 9.9 months (range, 5.1 to 33.5 months). The mean overall follow-up
      period for the open group was 9.5 months (range, 4.7 to 49.2 months). There was
      no significant difference in overall follow-up duration between groups (P =
      .627). A significantly increased incidence of postoperative stiffness was found
      in the arthroscopic group compared with the open group (17.9% v 5.6%, P = .002).
      Within the arthroscopic group, patients with postoperative stiffness were more
      frequently female patients than those without stiffness (63.2% v 33.3%, P = .016)
      and were more likely to be smokers than those without stiffness (36.8% v 16.1%, P
      = .040). The tenodesis site was located significantly more proximal in the
      arthroscopic group of patients with postoperative stiffness compared with
      patients without postoperative stiffness (32.44 +/- 7.8 mm from the top of the
      humeral head v 50.34 +/- 7.8 mm, P < .0001). CONCLUSIONS: Our results show a
      notably increased incidence of postoperative stiffness after arthroscopic
      suprapectoral biceps tenodesis compared with open subpectoral biceps tenodesis.
      This appears to occur more commonly in female patients and smokers and may have a
      relation to the position of the tenodesis, with a more superiorly placed
      tenodesis site being a potential influencing factor. On the basis of this series,
      this complication most commonly will improve over time and with symptom-based
      management. LEVEL OF EVIDENCE: Level III, therapeutic case-control study.

PMID- 24856766
TI  - Gomez-Lopez-Hernandez syndrome in a Japanese patient: a case report.
AB  - Gomez-Lopez-Hernandez syndrome (GLHS) is a rare neurocutaneous syndrome
      characterized by the triad of rhombencephalosynapsis, trigeminal anesthesia, and
      bilateral parieto-occipital alopecia. We herein describe the first Japanese
      patient with GLHS characterized by the standard triad with typical craniofacial
      anomaly including hypertelorism, brachyturricephaly and midface retrusion, and a
      short stature. This female patient had also exhibited fever-induced convulsive
      seizures and psychomotor developmental delay since infancy. Brain magnetic
      resonance imaging showed severe rhombencephalosynapsis, supratentorial
      abnormalities (aplasia of the septum pellucidum, severe ventricular enlargement,
      and hypoplasia of the corpus callosum), and hippocampus atrophy. Bilateral
      ectopic cerebellums were also observed. This report describes the long-term
      clinical outcome of GLHS and a new neuroradiological finding regarding
      rhombencephalosynapsis. 

PMID- 24856767
TI  - In vivo and in vitro anti-tumor and anti-metastasis effects of Coriolus
      versicolor aqueous extract on mouse mammary 4T1 carcinoma.
AB  - Coriolus versicolor (CV), a medicinal mushroom widely consumed in Asian
      countries, has been demonstrated to be effective in stimulation of immune system
      and inhibition of tumor growth. The present study aimed to investigate the anti
      tumor and anti-metastasis effects of CV aqueous extract in mouse mammary
      carcinoma 4T1 cells and in 4T1-tumor bearing mouse model. Our results showed that
      CV aqueous extract (0.125-2 mg/ml) did not inhibit 4T1 cell proliferation while
      the non-cytotoxic dose of CV extract (1-2 mg/ml) significantly inhibited cell
      migration and invasion (p<0.05). Besides, the enzyme activities and protein
      levels of MMP-9 were suppressed by CV extract significantly. Animal studies
      showed that CV aqueous extract (1 g/kg, orally-fed daily for 4 weeks) was
      effective in decreasing the tumor weight by 36%, and decreased the lung
      metastasis by 70.8% against untreated control. Besides, micro-CT analysis of the
      tumor-bearing mice tibias indicated that CV extract was effective in bone
      protection against breast cancer-induced bone destruction as the bone volume was
      significantly increased. On the other hand, CV aqueous extract treatments
      resulted in remarkable immunomodulatory effects, which was reflected by the
      augmentation of IL-2, 6, 12, TNF-alpha and IFN-gamma productions from the spleen
      lymphocytes of CV-treated tumor-bearing mice. In conclusion, our results
      demonstrated for the first time that the CV aqueous extract exhibited anti-tumor,
      anti-metastasis and immunomodulation effects in metastatic breast cancer mouse
      model, and could protect the bone from breast cancer-induced bone destruction.
      These findings provided scientific evidences for the clinical application of CV
      aqueous extract in breast cancer patients.

PMID- 24856768
TI  - Tetrandrine and fangchinoline, bisbenzylisoquinoline alkaloids from Stephania
      tetrandra can reverse multidrug resistance by inhibiting P-glycoprotein activity
      in multidrug resistant human cancer cells.
AB  - The overexpression of ABC transporters is a common reason for multidrug
      resistance (MDR) in cancer cells. In this study, we found that the isoquinoline
      alkaloids tetrandrine and fangchinoline from Stephania tetrandra showed a
      significant synergistic cytotoxic effect in MDR Caco-2 and CEM/ADR5000 cancer
      cells in combination with doxorubicin, a common cancer chemotherapeutic agent.
      Furthermore, tetrandrine and fangchinoline increased the intracellular
      accumulation of the fluorescent P-glycoprotein (P-gp) substrate rhodamine 123
      (Rho123) and inhibited its efflux in Caco-2 and CEM/ADR5000 cells. In addition,
      tetrandrine and fangchinoline significantly reduced P-gp expression in a
      concentration-dependent manner. These results suggest that tetrandrine and
      fangchinoline can reverse MDR by increasing the intracellular concentration of
      anticancer drugs, and thus they could serve as a lead for developing new drugs to
      overcome P-gp mediated drug resistance in clinic cancer therapy. 

PMID- 24856774
TI  - Standards of Care for Cystic Fibrosis ten years later.

PMID- 24856775
TI  - European Cystic Fibrosis Society Standards of Care: Best Practice guidelines.
AB  - Specialised CF care has led to a dramatic improvement in survival in CF: in the
      last four decades, well above what was seen in the general population over the
      same period. With the implementation of newborn screening in many European
      countries, centres are increasingly caring for a cohort of patients who have
      minimal lung disease at diagnosis and therefore have the potential to enjoy an
      excellent quality of life and an even greater life expectancy than was seen
      previously. To allow high quality care to be delivered throughout Europe, a
      landmark document was published in 2005 that sets standards of care. Our current
      document builds on this work, setting standards for best practice in key aspects
      of CF care. The objective of our document is to give a broad overview of the
      standards expected for screening, diagnosis, pre-emptive treatment of lung
      disease, nutrition, complications, transplant/end of life care and psychological
      support. For comprehensive details of clinical care of CF, references to the most
      up to date European Consensus Statements, Guidelines or Position Papers are
      provided in Table 1. We hope that this best practice document will be useful to
      clinical teams both in countries where CF care is developing and those with
      established CF centres. 

PMID- 24856776
TI  - European Cystic Fibrosis Society Standards of Care: Framework for the Cystic
      Fibrosis Centre.
AB  - A significant increase in life expectancy in successive birth cohorts of people
      with cystic fibrosis (CF) is a result of more effective treatment for the
      disease. It is also now widely recognized that outcomes for patients cared for in
      specialist CF Centres are better than for those who are not. Key to the
      effectiveness of the specialist CF Centre is the multidisciplinary team (MDT),
      which should include consultants, clinical nurse specialist, microbiologist,
      physiotherapist, dietitian, pharmacist, clinical psychologist, social worker,
      clinical geneticist and allied healthcare professionals, all of whom should be
      experienced in CF care. Members of the MDT are also expected to keep up to date
      with developments in CF through continued professional development, attendance at
      conferences, auditing and involvement in research. Specialists CF Centres should
      also network with other Centres both nationally and internationally, and feed
      Centre data to registries in order to further the understanding of the disease.
      This paper provides a framework for the specialist CF Centre, including the
      organisation of the Centre and the individual roles of MDT members, as well as
      highlighting the value of CF organisations and disease registries. 

PMID- 24856777
TI  - European Cystic Fibrosis Society Standards of Care: Quality Management in cystic
      fibrosis.
AB  - Since the earliest days of cystic fibrosis (CF) treatment, patient data have been
      recorded and reviewed in order to identify the factors that lead to more
      favourable outcomes. Large data repositories, such as the US Cystic Fibrosis
      Registry, which was established in the 1960s, enabled successful treatments and
      patient outcomes to be recognized and improvement programmes to be implemented in
      specialist CF centres. Over the past decades, the greater volumes of data
      becoming available through Centre databases and patient registries led to the
      possibility of making comparisons between different therapies, approaches to care
      and indeed data recording. The quality of care for individuals with CF has become
      a focus at several levels: patient, centre, regional, national and international.
      This paper reviews the quality management and improvement issues at each of these
      levels with particular reference to indicators of health, the role of CF Centres,
      regional networks, national health policy, and international data registration
      and comparisons. 

PMID- 24856778
TI  - Super-twisting sliding mode differentiation for improving PD controllers
      performance of second order systems.
AB  - Designing a proportional derivative (PD) controller has as main problem, to
      obtain the derivative of the output error signal when it is contaminated with
      high frequency noises. To overcome this disadvantage, the supertwisting algorithm
      (STA) is applied in closed-loop with a PD structure for multi-input multi-output
      (MIMO) second order nonlinear systems. The stability conditions were analyzed in
      terms of a strict non-smooth Lyapunov function and the solution of Riccati
      equations. A set of numerical test was designed to show the advantages of
      implementing PD controllers that used STA as a robust exact differentiator. The
      first numerical example showed the stabilization of an inverted pendulum. The
      second example was designed to solve the tracking problem of a two-link robot
      manipulator. 

PMID- 24856779
TI  - Streptococcus suis infection and malignancy in man, Spain.

PMID- 24856688
TI  - Measurements of tt spin correlations and top-quark polarization using dilepton
      final states in pp collisions at sqrt[s]=7  TeV.
AB  - Spin correlations and polarization in the top quark-antiquark system are measured
      using dilepton final states produced in pp collisions at the LHC at sqrt[s]=7 
      TeV. The data correspond to an integrated luminosity of 5.0  fb(-1) collected
      with the CMS detector. The measurements are performed using events with two
      oppositely charged leptons (electrons or muons), a significant imbalance in
      transverse momentum, and two or more jets, where at least one of the jets is
      identified as originating from a b quark. The spin correlations and polarization
      are measured through asymmetries in angular distributions of the two selected
      leptons, unfolded to the parton level. All measurements are found to be in
      agreement with predictions of the standard model.

PMID- 24856780
TI  - Electropolymerized carbonic anhydrase immobilization for carbon dioxide capture.
AB  - Biomimetic carbonation carried out with carbonic anhydrase (CA) in CO2-absorbing
      solutions, such as methyldiethanolamine (MDEA), is one approach that has been
      developed to accelerate the capture of CO2. However, there are several practical
      issues, such as high cost and limited enzyme stability, that need to be overcome.
      In this study, the capacity of CA immobilization on a porous solid support was
      studied to improve the instability in the tertiary amine solvent. We have shown
      that a 63% porosity macroporous carbon foam support makes separation and reuse
      facile and allows for an efficient supply and presentation of CO2 to an aqueous
      solvent and the enzyme catalytic center. These enzymatic supports conserved 40%
      of their initial activity after 42 days at 70  degrees C in an amine solvent,
      whereas the free enzyme shows no activity after 1 h in the same conditions. In
      this work, we have overcome the technical barrier associated with the recovery of
      the biocatalyst after operation, and most of all, these electropolymerized
      enzymatic supports have shown a remarkable increase of thermal stability in an
      amine-based CO2 sequestration solvent. 

PMID- 24856781
TI  - New regulations for radiation protection for work involving radioactive fallout
      emitted by the TEPCO Fukushima Daiichi APP accident--disposal of contaminated
      soil and wastes.
AB  - The accident at the Fukushima Daiichi Atomic Power Plant that accompanied the
      Great East Japan Earthquake on March 11, 2011, released a large amount of
      radioactive material. To rehabilitate the contaminated areas, the government of
      Japan decided to carry out decontamination work and manage the waste resulting
      from decontamination. In the summer of 2013, the Ministry of the Environment
      planned to begin a full-scale process for waste disposal of contaminated soil and
      wastes removed as part of the decontamination work. The existing regulations were
      not developed to address such a large amount of contaminated wastes. The Ministry
      of Health, Labour and Welfare (MHLW), therefore, had to amend the existing
      regulations for waste disposal workers. The amendment of the general regulation
      targeted the areas where the existing exposure situation overlaps the planned
      exposure situation. The MHLW established the demarcation lines between the two
      regulations to be applied in each situation. The amendment was also intended to
      establish provisions for the operation of waste disposal facilities that handle
      large amounts of contaminated materials. Deliberation concerning the regulation
      was conducted when the facilities were under design; hence, necessary adjustments
      should be made as needed during the operation of the facilities. 

PMID- 24856784
TI  - Considerations around the introduction of a cholera vaccine in Bangladesh.
AB  - Cholera is an endemic and epidemic disease in Bangladesh. On 3 March 2013, a
      meeting on cholera and cholera vaccination in Bangladesh was convened by the
      Foundation Merieux jointly with the International Centre for Diarrhoeal Disease
      Research, Bangladesh (ICDDR, B). The purpose of the meeting was to discuss the
      investment case for cholera vaccination as a complimentary control and prevention
      strategy. The performance of a new low cost oral cholera vaccine, ShancholTM,
      used in recent trials in Bangladesh, was also reviewed in the context of a
      potential large-scale public-sector vaccination program. Findings showed the oral
      vaccine to be highly cost-effective when targeting ages 1-14 y, and cost
      effective when targeting ages 1+y, in high-burden/high-risk districts. Other
      vaccination strategies targeting urban slums and rural areas without improved
      water were found to be cost-effective. Regardless of cost-effectiveness (value),
      the budget impact (affordability) will be an important determinant of which
      target population and vaccination strategy is selected. Most importantly,
      adequate vaccine supply for the proposed vaccination programs must be addressed
      in the context of global efforts to establish a cholera vaccine stockpile and
      supply other control and prevention efforts.

PMID- 24856782
TI  - Evaluation of safety and immunogenicity of HNVAC, an MDCK-based H1N1 pandemic
      influenza vaccine, in Phase I single centre and Phase II/III multi-centre, double
      blind, randomized, placebo-controlled, parallel assignment studies.
AB  - The clinical evaluation of the MDCK-based H1N1 pandemic influenza vaccine HNVAC
      in adults aged 18-65 years is reported. In the Phase I randomized, double-blind,
      placebo-controlled, single-centre study, 160 subjects were parallelly assigned
      3:1 to vaccine:placebo groups (n=60:20) with both the aluminium hydroxide
      adjuvanted and non-adjuvanted vaccine formulations. A single dose of both the
      formulations containing 15 MUg of haemagglutinin protein showed minimal adverse
      reactions, the most common of which were pain at injection site (11.67%) and
      fever (10.00%). Both formulations produced 74-81% seroprotection (SRP: titre of
      >=40), 67-70% seroconversion (SRC: four-fold increase in titres between days 0
      and 21), and a four-fold increase in geometric mean titres (GMT). Aluminium
      hydroxide did not have a significant effect either on immunogenicity or on
      reactogenicity. Nevertheless, based on its recognized positive effects on the
      stability and immunogenicity of many vaccines, and its marginal benefit in both
      pre-clinical and Phase I studies of HNVAC, alum adjuvanted HNVAC was further
      tested in a staggered Phase II/III randomized, double-blind, placebo-controlled,
      multi-centre study of 200 and 195 subjects, respectively, parallelly assigned 4:1
      to adjuvanted vaccine and placebo groups. In these studies, the most common
      adverse reactions were pain at injection site (6.88% and 5.77% in Stage 1 and
      Stage 2, respectively) and fever (7.50% and 7.05%, respectively), and a single
      dose resulted in 87-90% SRP, 85-86% SRC, and a nearly six-fold increase in GMT,
      meeting or exceeding licensing criteria. It is concluded that HNVAC is safe and
      immunogenic to adults of 18-65 years.

PMID- 24856785
TI  - Freeze-thaw stress of Alhydrogel (r) alone is sufficient to reduce the
      immunogenicity of a recombinant hepatitis B vaccine containing native antigen.
AB  - Preventing losses in vaccine potency due to accidental freezing has recently
      become a topic of interest for improving vaccines. All vaccines with aluminum
      containing adjuvants are susceptible to such potency losses. Recent studies have
      described excipients that protect the antigen from freeze-induced inactivation,
      prevent adjuvant agglomeration and retain potency. Although these strategies have
      demonstrated success, they do not provide a mechanistic understanding of freeze
      thaw (FT) induced potency losses. In the current study, we investigated how
      adjuvant frozen in the absence of antigen affects vaccine immunogenicity and
      whether preventing damage to the freeze-sensitive recombinant hepatitis B surface
      antigen (rHBsAg) was sufficient for maintaining vaccine potency. The final
      vaccine formulation or Alhydrogel((r)) alone was subjected to three FT-cycles.
      The vaccines were characterized for antigen adsorption, rHBsAg tertiary
      structure, particle size and charge, adjuvant elemental content and in-vivo
      potency. Particle agglomeration of either vaccine particles or adjuvant was
      observed following FT-stress. In vivo studies demonstrated no statistical
      differences in IgG responses between vaccines with FT-stressed adjuvant and no
      adjuvant. Adsorption of rHBsAg was achieved; regardless of adjuvant treatment,
      suggesting that the similar responses were not due to soluble antigen in the
      frozen adjuvant-containing formulations. All vaccines with adjuvant, including
      the non-frozen controls, yielded similar, blue-shifted fluorescence emission
      spectra. Immune response differences could not be traced to differences in the
      tertiary structure of the antigen in the formulations. Zeta potential
      measurements and elemental content analyses suggest that FT-stress resulted in a
      significant chemical alteration of the adjuvant surface. This data provides
      evidence that protecting a freeze-labile antigen from subzero exposure is
      insufficient to maintain vaccine potency. Future studies should focus on adjuvant
      protection. To our knowledge, this is the first study to systematically
      investigate how FT-stress to adjuvant alone affects immunogenicity. It provides
      definitive evidence that this damage is sufficient to reduce vaccine potency. 

PMID- 24856783
TI  - Development of a novel, guinea pig-specific IFN-gamma ELISPOT assay and
      characterization of guinea pig cytomegalovirus GP83-specific cellular immune
      responses following immunization with a modified vaccinia virus Ankara (MVA)
      vectored GP83 vaccine.
AB  - The guinea pig (Cavia porcellus) provides a useful animal model for studying the
      pathogenesis of many infectious diseases, and for preclinical evaluation of
      vaccines. However, guinea pig models are limited by the lack of immunological
      reagents required for characterization and quantification of antigen-specific T
      cell responses. To address this deficiency, an enzyme-linked immunospot (ELISPOT)
      assay for guinea pig interferon (IFN)-gamma was developed to measure
      antigen/epitope-specific T cell responses to guinea pig cytomegalovirus (GPCMV)
      vaccines. Using splenocytes harvested from animals vaccinated with a modified
      vaccinia virus Ankara (MVA) vector encoding the GPCMV GP83 (homolog of human CMV
      pp65 [gpUL83]) protein, we were able to enumerate and map antigen-specific
      responses, both in vaccinated as well as GPCMV-infected animals, using a panel of
      GP83-specific peptides. Several potential immunodominant GP83-specific peptides
      were identified, including one epitope, LGIVHFFDN, that was noted in all guinea
      pigs that had a detectable CD8+ response to GP83. Development of a guinea pig IFN
      gamma ELISPOT should be useful in characterization of additional T cell-specific
      responses to GPCMV, as well as other pathogens. This information in turn can help
      focus future experimental evaluation of immunization strategies, both for GPCMV
      as well as for other vaccine-preventable illnesses studied in the guinea pig
      model.

PMID- 24856786
TI  - Editorial: Antibacterial targets for the 21st century.

PMID- 24856787
TI  - Lessons learned from different approaches towards classifying personal factors.
AB  - PURPOSE: To examine and compare existing suggestions towards a classification of
      Personal Factors (PF) of the International Classification of Functioning,
      Disability and Health (ICF). METHODS: Qualitative and quantitative content
      analyses of available categorizations of PF are conducted. RESULTS: While the
      eight categorizations greatly differ in their background and structure, the broad
      content areas covered seem to be similar and reflect the ICF definition of PF.
      They cover to various degrees 12 broad content areas: socio-demographic factors,
      behavioral and lifestyle factors, cognitive psychological factors, social
      relationships, experiences and biography, coping, emotional factors,
      satisfaction, other health conditions, biological/physiological factors,
      personality, motives/motivation. CONCLUSIONS: In comparing these categorizations,
      a common core of content issues for a potential ICF PF classification could be
      identified and valuable lessons learned. This can contribute to future
      classification development activities in relation to PF.

PMID- 24856788
TI  - Validation of the Caregiver Priorities and Child Health Index of Life with
      Disabilities (CPCHILD) in a sample of Dutch non-ambulatory children with cerebral
      palsy.
AB  - PURPOSE: To assess the reliability and validity of the Caregiver Priorities and
      Child Health Index of Life with Disabilities (CPCHILD)-Dutch Version, a proxy
      measure of health status and well-being of non-ambulatory children with cerebral
      palsy (CP). METHODS: Parents (n = 66) of 47 boys/19 girls between 5 and 18 years
      with CP (GMFCS IV-V) participated. To assess the reliability each domain and the
      total measure was tested for internal consistency, test-retest and inter-rater
      reliability. Known-groups validity of the CPCHILD-DV was assessed by comparing
      mean scores of clinically distinct subgroups and convergent validity by
      correlating the CPCHILD-DV with the TNO-AZL Preschool Children Quality of Life
      (TAPQOL). RESULTS: The mean CPCHILD-DV total score was 52.0 (SD11.5). Test-retest
      reliability of the total score as assessed by intraclass correlations (ICC) was
      0.73 (domains: 0.55-0.80). For the inter-rater reliability the ICC was 0.64
      (domains: 0.58-0.90); the Cronbach's alpha's ranged from 0.60 to 0.95. The
      CPCHILD score could differentiate between GMFCS levels and between subgroups of
      cognitive level in the domain "communication and social interaction". There were
      moderate significant correlations (range r(s): 0.31-0.50) between sections of
      CPCHILD-DV and TAPQOL. CONCLUSIONS: The CPCHILD-DV has sufficient reliability and
      validity as a proxy measure of health status and well-being of non-ambulatory
      children with CP.

PMID- 24856789
TI  - The experience of medical and rehabilitation intervention for traumatic hand
      injuries in rural and remote North Queensland: a qualitative study.
AB  - INTRODUCTION: This research explored the experience of receiving medical and
      rehabilitation intervention for rural and remote residents in North Queensland,
      Australia who had experienced a traumatic hand injury. This study contributes to
      larger project that seeks to propose a model of service delivery to rural and
      remote residents who have sustained a traumatic injury. METHODS: Utilising an
      interpretive phenomenological research design, data was gathered through in
      depth, semi-structured interviews. Fifteen participants were recruited into this
      study and questions were designed to explore the experience of receiving medical
      and rehabilitation intervention following a traumatic hand injury for residents
      in rural and remote areas of North Queensland. RESULTS: The major themes that
      emerged were experience of medical intervention, experience of rehabilitation,
      travel, and technology. Participants felt that medical practitioners had a lack
      of local knowledge and were concerned that delays in medical intervention
      resulted in ongoing impairment. They reported following the exercise program they
      were given, often modifying it to fit with their daily routine. Metropolitan
      therapists appeared to have limited understanding of issues relevant to rural and
      remote lifestyles. There was, quite often, no occupational therapist or
      physiotherapist at their local facility due to staff turnover, and, when
      available, they had limited experience in hand injuries. The distance and cost of
      travel to appointments were of significant concern. The use of telehealth or
      telerehabilitation received a mixed response. CONCLUSION: Findings highlight the
      concerns regarding the provision of healthcare to rural and remote residents
      following a traumatic hand injury. These results provide the basis for
      recommendations surrounding the development of programs and service delivery
      models to address diverse needs in rural and remote areas.

PMID- 24856790
TI  - Ankle fractures and employment: a life-changing event for patients.
AB  - PURPOSE: Ankle fractures, one of the most common types of orthopaedic injury,
      have been associated with reduced functional outcome and significant changes in
      long-term employment. Although information on unemployment following ankle
      fractures can be important in cases of financial compensation, no studies have
      investigated rates of short-term disability and employment status among patients
      who have suffered isolated ankle fractures in the US. METHOD: We retrospectively
      reviewed 573 medical charts for patients who were treated for ankle fractures in
      the last 3 years at a level I trauma center. A total of 83 non-elderly patients
      that had isolated ankle fractures were contacted and surveyed over the phone.
      Patients were asked about employment history and current status, disability, type
      of fracture, and demographic information. RESULTS: Fifty-three (62%) patients
      contacted were employed at the time of injury. In all, 34% (n = 18) of patients
      lost their job because of their injury, of which only 8 (44%) received new
      employment. A total of 15% (n = 8) of patients that were previously employed
      decided to no longer return to work. Ten patients (56%) received disability
      status. CONCLUSIONS: Ankle fracture patients are likely to suffer high rates of
      unemployment or disability shortly after their injury. Further investigations
      with a larger-scale, randomized patient population can provide important
      information on employment status following ankle fractures.

PMID- 24856791
TI  - Altered tibiofemoral joint contact mechanics and kinematics in patients with knee
      osteoarthritis and episodic complaints of joint instability.
AB  - BACKGROUND: To evaluate knee joint contact mechanics and kinematics during the
      loading response phase of downhill gait in knee osteoarthritis patients with self
      reported instability. METHODS: Forty-three subjects, 11 with medial compartment
      knee osteoarthritis and self-reported instability (unstable), 7 with medial
      compartment knee osteoarthritis but no reports of instability (stable), and 25
      without knee osteoarthritis or instability (control) underwent Dynamic Stereo X
      ray analysis during a downhill gait task on a treadmill. FINDINGS: The medial
      compartment contact point excursions were longer in the unstable group compared
      to the stable (P=0.046) and the control groups (P=0.016). The peak medial
      compartment contact point velocity was also greater for the unstable group
      compared to the stable (P=0.047) and control groups (P=0.022). Additionally, the
      unstable group demonstrated a coupled movement pattern of knee extension and
      external rotation after heel contact which was different than the coupled motion
      of knee flexion and internal rotation demonstrated by stable and control groups.
      INTERPRETATION: Our findings suggest that knee joint contact mechanics and
      kinematics are altered during the loading response phase of downhill gait in knee
      osteoarthritis patients with self-reported instability. The observed longer
      medial compartment contact point excursions and higher velocities represent
      objective signs of mechanical instability that may place the arthritic knee joint
      at increased risk for disease progression. Further research is indicated to
      explore the clinical relevance of altered contact mechanics and kinematics during
      other common daily activities and to assess the efficacy of rehabilitation
      programs to improve altered joint biomechanics in knee osteoarthritis patients
      with self-reported instability.

PMID- 24856792
TI  - Increased range of motion after static stretching is not due to changes in muscle
      and tendon structures.
AB  - BACKGROUND: It is known that static stretching is an appropriate means of
      increasing the range of motion, but information in the literature about the
      mechanical adaptation of the muscle-tendon unit is scarce. Therefore, the purpose
      of this study was to investigate the influence of a six-week static stretching
      training program on the structural and functional parameters of the human
      gastrocnemius medialis muscle and the Achilles tendon. METHODS: A total of 49
      volunteers were randomly assigned into static stretching and control groups.
      Before and following the stretching intervention, we determined the maximum
      dorsiflexion range of motion with the corresponding fascicle length and pennation
      angle. Passive resistive torque and maximum voluntary contraction were measured
      with a dynamometer. Muscle-tendon junction displacement allowed us to determine
      the length changes in tendon and muscle, and hence to calculate stiffness.
      Fascicle length, pennation angle, and muscle tendon junction displacement were
      measured with ultrasound. FINDINGS: Mean range of motion increased significantly
      from 30.9 (5.3) to 36.3 (6.1) in the intervention group, but other functional
      (passive resistive torque, maximum voluntary contraction) and structural
      (fascicle length, pennation angle, muscle stiffness, tendon stiffness) parameters
      were unaltered. INTERPRETATION: The increased range of motion could not be
      explained by the structural changes in the muscle-tendon unit, and was likely due
      to increased stretch tolerance possibly due to adaptations of nociceptive nerve
      endings.

PMID- 24856793
TI  - Primary lung cancer in lung transplant recipients.
AB  - Risk factors for lung cancer in lung transplant recipients are a history of
      smoking and immunosuppression, to which adds increasing use of lungs from donors
      with a smoking history. The three typical presentations are incidental diagnosis
      on the explanted lung, concerning less than 2%; lung cancer developing on the
      lung graft, accounting for less than 1%; and incidence of lung cancer on the
      native lung, estimated at 9%. Treatment along available guidelines may be
      hampered by decreased lung function owing to chronic rejection or adverse effects
      of immunosuppression. Prognosis is comparable to a general population in resected
      stage I cancer and is less favorable in advanced stages. 

PMID- 24856794
TI  - In vivo testing of a novel blood pump for short-term extracorporeal life support.
AB  - BACKGROUND: Centrifugal pumps are used increasingly for temporary mechanical
      support for the treatment of cardiogenic shock. However, centrifugal pumps can
      generate excessive negative pressure and are afterload sensitive. A previously
      developed modified roller pump mitigates these limitations both in vitro and in
      preliminary animal experiments. We report the results of intermediate-term
      testing of our evolving pump technology, known as the BioVAD. METHODS: The BioVAD
      was implanted in 6 adult male sheep (62.5+/-3.9 kg), with drainage from the left
      atrium and reinfusion into the descending aorta. The sheep were monitored for 5
      days. Heparin was given during the initial implantation, but no additional
      anticoagulants were given. Data collected included hemodynamic status, pump flow
      and pressures, laboratory values to monitor end-organ function and hemolysis,
      pathologic specimens to evaluate for thromboembolic events and organ ischemia,
      and explanted pump evaluation results. RESULTS: All animals survived the planned
      experimental duration and there were no pump malfunctions. Mean BioVAD flow was
      3.57+/-0.30 L/min (57.1 mL/kg/min) and mean inlet pressure was -30.51+/-4.25 mm
      Hg. Laboratory values, including plasma free hemoglobin, creatinine, lactate, and
      bilirubin levels, remained normal. Three animals had small renal cortical
      infarcts, but there were no additional thromboembolic events or other
      abnormalities seen on pathologic examination. No thrombus was identified in the
      BioVAD blood flow path. CONCLUSIONS: The BioVAD performed well for 5 days in this
      animal model of temporary left ventricular assistance. Its potential advantages
      over centrifugal pumps may make it applicable for short-term mechanical
      circulatory support.

PMID- 24856795
TI  - Professional and social support enhances maternal well-being in women with
      intellectual disability - a Swedish interview study.
AB  - OBJECTIVE: to gain a deeper understanding of the experience of professional and
      social support during pregnancy and childbirth among women with intellectual
      disability (ID) in Sweden. DESIGN/SETTING: an interview study among 10 women with
      ID, who had given birth within seven years. Two interviews were performed with
      each woman and data were analysed with qualitative content analysis. FINDINGS:
      the overarching theme was: Professional and social support enhances maternal well
      being in women with intellectual disability. The women described that the midwife
      and other caregivers contributed to their own insights and supported their mother
      to-be process. They were mostly satisfied with the professional care and support
      during pregnancy and childbirth, based on aspects such as continuity, competence
      and professional experience of the midwives but also professional approach and
      working methods. Dissatisfaction and confusion occurred when questions were left
      unanswered or when the women's special needs were not taken into consideration.
      Family members, friends and colleagues could also have a supporting role and,
      together with the health staff, contribute to the well-being of the woman.
      CONCLUSIONS: if professional support and care from midwives and other caregivers
      is adapted to the special needs of women with ID, it contributes to new insights,
      enhances well-being and supports the process of becoming a mother. Midwife-led
      continuity of care together with continuous social support should be offered to
      pregnant women with ID during pregnancy and childbirth.

PMID- 24856796
TI  - Effects of dexmedetomidine on the ratio of T helper 1 to T helper 2 cytokines in
      patients undergoing laparoscopic cholecystectomy.
AB  - STUDY OBJECTIVES: To investigate the effect of dexmedetomidine on T helper 1
      (Th1) and T helper 2 (Th2) cytokines and their ratio during and after surgery.
      DESIGN: Single-blinded, randomized, placebo-controlled clinical comparison study.
      SETTING: Academic medical center. PATIENTS: 46 adult, ASA physical status 1 and 2
      patients scheduled for laparoscopic cholecystectomy. INTERVENTIONS: Patients were
      randomized to two groups: the dexmedetomidine group (n = 23), in which
      dexmedetomidine was infused with a 1.0 MUg/kg loading dose followed by infusion
      of 0.5 MUg/kg/h; or the saline group (n = 23). MEASUREMENTS: Interferon-gamma
      (IFN-gamma) and interleukin-4 (IL-4) as Th1 and Th2 cytokines, respectively, were
      quantified three times: after induction of anesthesia (T0), at the end of
      peritoneal closure (T1), and 60 minutes after surgery (T2). The IFN-gamma/IL-4
      ratio was then calculated. MAIN RESULTS: The dexmedetomidine group displayed
      higher levels of IFN-gamma at T1 and T2 (42.30 pg/dL vs 6.91 pg/dL at T1 [P =
      0.025]; 40.51 pg/dL vs 8.29 pg/dL at T2 [P = 0.030]) than the saline group. The
      dexmedetomidine group was also associated with higher ratios of IFN-gamma/IL-4
      (1.22 vs 0.32, respectively, at T1 [P = 0.012]; 1.53 vs 0.13, respectively, at T2
      [P = 0.012]). CONCLUSIONS: Dexmedetomidine plays an immunomodulatory role,
      shifting the Th1/Th2 cytokine balance toward Th1 in patients with surgical and
      anesthetic stress.

PMID- 24856797
TI  - Thoracic paravertebral anesthesia for percutaneous radiofrequency ablation of
      hepatic tumors.
AB  - STUDY OBJECTIVE: To present our preliminary experience using a thoracic
      paravertebral block (TPVB) as the sole anesthetic in percutaneous hepatic
      radiofrequency ablation (RFA). DESIGN: Retrospective case series of 12 ASA
      physical status 1, 2, and 3 patients of average risk scheduled for RFA. SETTING:
      University medical center. MEASUREMENTS: The first 12 procedures performed using
      TPVB were analyzed to evaluate the efficacy and safety of this anesthetic
      technique. Data collected included patients' characteristics, procedure, pain
      referred during paravertebral punctures, and RFA (verbal numerical scale; VNS).
      Anesthesia and medical records also were reviewed for any major complications
      that occurred during or after the RFA. MAIN RESULTS: Ten of the 12 patients
      presented for hepatocellular carcinoma; the other two patients had melanoma
      metastasis. Nine patients were ASA physical status 1 or 2; the other three
      patients were ASA physical status 3. Nine had liver cirrhosis. All patients had
      normal coagulation profiles. The TPVBs were performed in a median time of 6.5 (4
      15) minutes. Onset of sensory loss to pinprick test occurred approximately 15 to
      20 minutes after the injections. No evidence of bilateral blockade was seen in
      any patient. In most cases, the extent of anesthesia ranged from T6 to T11 or
      T12. In one patient (no. 2), the stimulating needle elicited no sensory or motor
      response at the T7 level; the local anesthetic was then injected one cm beyond
      the transverse process. All patients were very pleased with their anesthetic
      care; all were discharged from the hospital with no procedure-related
      complications. CONCLUSION: The use of thoracic paravertebral block as the sole
      anesthetic for RFA of liver produced satisfactory unilateral anesthesia and minor
      adverse events.

PMID- 24856798
TI  - Are anesthesia start and end times randomly distributed? The influence of
      electronic records.
AB  - STUDY OBJECTIVE: To perform a frequency analysis of start minute digits (SMD) and
      end minute digits (EMD) taken from the electronic, computer-assisted, and manual
      anesthesia billing-record systems. DESIGN: Retrospective cross-sectional review.
      SETTING: University medical center. MEASUREMENTS: This cross-sectional review was
      conducted on billing records from a single healthcare institution over a 15-month
      period. A total of 30,738 cases were analyzed. For each record, the start time
      and end time were recorded. Distributions of SMD and EMD were tested against the
      null hypothesis of a frequency distribution equivalently spread between zero and
      nine. MAIN RESULTS: SMD and EMD aggregate distributions each differed from
      equivalency (P < 0.0001). When stratified by type of anesthetic record, no
      differences were found between the recorded and expected equivalent distribution
      patterns for electronic anesthesia records for start minute (P < 0.98) or end
      minute (P < 0.55). Manual and computer-assisted records maintained nonequivalent
      distribution patterns for SMD and EMD (P < 0.0001 for each comparison).
      Comparison of cumulative distributions between SMD and EMD distributions
      suggested a significant difference between the two patterns (P < 0.0001).
      CONCLUSION: An electronic anesthesia record system, with automated time capture
      of events verified by the user, produces a more unified distribution of billing
      times than do more traditional methods of entering billing times.

PMID- 24856800
TI  - What a tangled web we weave: How technology is reshaping pedagogy.

PMID- 24856799
TI  - Hepatitis E virus infection, Papua New Guinea, Fiji, and Kiribati, 2003-2005.

PMID- 24856801
TI  - Tensions and ambiguities: A qualitative study of final year adult field nursing
      students' experiences of caring for people affected by advanced dementia in
      Wales, UK.
AB  - BACKGROUND: Rising dementia prevalence means that general nurses globally will
      encounter more people affected by advanced dementia. Advanced dementia care is
      profoundly complex yet there is a paucity of research exploring how general
      nursing students experience and thus learn to care for those affected.
      OBJECTIVES: To explore final year nursing students' (adult field) experiences of
      caring for people affected by advanced dementia. DESIGN: A qualitative design was
      adopted. SETTING: The setting was Wales, UK. PARTICIPANTS: Eleven final year
      nursing undergraduates (adult field). METHOD: Data were collected using digitally
      recorded one-to-one in-depth interviews in 2013 and analysed using thematic
      analysis. RESULTS: Participants' experiences fell within three main themes: they
      can be quite challenging; a lot of dementia patients are seen as hazards and it's
      not all about doing stuff. Participants aspired to person-centred care. However,
      they felt insufficiently prepared for what they believed was knowledgeable work
      requiring interpersonal competence and confidence. Participants appreciated that
      many practitioners, their clinical educators, were insufficiently prepared for
      advanced dementia care. CONCLUSIONS: The study provided further evidence of the
      complexity of caring for those with advanced dementia and associated theory,
      practice and policy gaps. There are important implications for education in terms
      of curriculum development and learning from and in practice.

PMID- 24856802
TI  - Effect of ischemic postconditioning on microvascular obstruction in reperfused
      myocardial infarction. Results of a randomized study in patients and of an
      experimental model in swine.
AB  - BACKGROUND: Ischemic postconditioning (PCON) appears as a potentially beneficial
      tool in ST-segment elevation myocardial infarction (STEMI). We evaluated the
      effect of PCON on microvascular obstruction (MVO) in STEMI patients and in an
      experimental swine model. METHODS: A prospective randomized study in patients and
      an experimental study in swine were carried out in two university hospitals in
      Spain. 101 consecutive STEMI patients were randomized to undergo primary
      angioplasty followed by PCON or primary angioplasty alone (non-PCON). Using late
      gadolinium enhancement cardiovascular magnetic resonance, infarct size and MVO
      were quantified (% of left ventricular mass). In swine, using an angioplasty
      balloon-induced anterior STEMI model, MVO was defined as the % of area at risk
      without thioflavin-S staining. RESULTS: In patients, PCON (n=49) in comparison
      with non-PCON (n=52) did not significantly reduce MVO (0 [0-1.02]% vs. 0 [0-2.1]%
      p=0.2) or IS (18 +/- 13% vs. 21 +/- 14%, p=0.2). MVO (>1 segment in the 17
      segment model) occurred in 12/49 (25%) PCON and in 18/52 (35%) non-PCON patients,
      p=0.3. No significant differences were observed between PCON and non-PCON
      patients in left ventricular volumes, ejection fraction or the extent of
      hemorrhage. In the swine model, MVO occurred in 4/6 (67%) PCON and in 4/6 (67%)
      non-PCON pigs, p=0.9. The extent of MVO (10 +/- 7% vs. 10 +/- 8%, p=0.9) and
      infarct size (23 +/- 14% vs. 24 +/- 10%, p=0.8) was not reduced in PCON compared
      with non-PCON pigs. CONCLUSIONS: Ischemic postconditioning does not significantly
      reduce microvascular obstruction in ST-segment elevation myocardial infarction.
      Clinical Trial Registration http://www.clinicaltrials.gov. Unique identifier:
      NCT01898546.

PMID- 24856803
TI  - Impact of non-cardiovascular disease comorbidity on cardiovascular disease
      symptom severity: a population-based study.
AB  - OBJECTIVES: Non-cardiovascular comorbidity is common in cardiovascular disease
      (CVD) populations but its influence on chest pain (CP) and shortness of breath
      (SOB) symptom-specific physical limitations is unknown. We wanted to test the a
      priori hypothesis that an unrelated comorbidity would influence symptom-specific
      physical limitations and to investigate this impact in different severities of
      CVD. METHOD AND RESULTS: The study was based on 5426 patients from ten family
      practices, organised into eight a priori exclusive severity groups: (i) no CVD or
      osteoarthritis (OA) (reference), (ii) index hypertension, ischaemic heart disease
      (IHD) and heart failure (HF) without OA, (iii) index OA without CVD and (iv) same
      CVD groups with comorbid OA. The measure of CP physical limitations was Seattle
      Angina Questionnaire and for SOB physical limitations was the Kansas City
      Cardiomyopathy Questionnaire. Adjusted baseline associations between the cohorts
      and symptom-specific physical limitations were assessed using linear regression
      methods. In the study population, 1443 (27%) reported CP and 2097 (39%) SOB. CP
      and SOB physical limitations increased with CVD severity in the index and
      comorbid groups. Compared with the respective index CVD group, the CP physical
      limitation scores for comorbid CVD groups with OA were lower by: -14.7 (95% CI 
      21.5, 7.8) for hypertension, -5.5 (-10.4, -0.7) for IHD and -22.1 (-31.0, -6.7)
      for HF. For SOB physical limitations, comorbid scores were lower by: -9.2 (-13.8,
      -4.6) for hypertension, -6.4 (-11.1, -1.8) for IHD and -8.8 (-19.3, 1.65) for HF.
      CONCLUSIONS: CP and SOB are common symptoms, and OA increases the CVD symptom
      specific physical limitations additively. Comorbidity interventions need to be
      developed for CVD specific health outcomes.

PMID- 24856804
TI  - Arterial function can be obtained by noninvasive finger pressure waveform.

PMID- 24856805
TI  - Cognitive impairment and cardiovascular disease: so near, so far.
AB  - In the spectrum of cognitive impairment, ranging from "pure" vascular dementia to
      Alzheimer's disease (AD), clinical interest has recently expanded from the brain
      to also include the vessels, shifting the pathophysiological focus from the
      leaves of synaptic dysfunction to the sap of cerebral microcirculation and the
      roots of cardiovascular function. From a diagnostic viewpoint, a thorough
      clinical evaluation of individuals presenting cognitive impairment might
      systematically include the assessment of the major cardiovascular rings of the
      chain linking regional perfusion to brain function: 1) lung (with assessment of
      asthma, chronic obstructive pulmonary disease, obstructive sleep apnea syndrome);
      2) heart function (with clinical examination and echocardiography) and
      cardiovascular risk factors; 3) orthostatic hypotension (with medical history and
      measurement of heart rate and blood pressure in supine and upright positions); 4)
      aorta and large artery stiffness (with assessment of pulse wave velocity); 5)
      large cerebro-vascular vessel status (with neuroimaging techniques); 6)
      assessment of microcirculation (with cerebrovascular reactivity testing with
      transcranial Doppler sonography or MRI perfusion imaging); and 7) assessment of
      venous cerebral circulation. The apparent difference in approaches to "brain" and
      "vascular" environmental enrichment with physical, cognitive and sensorial
      training is conceptually identical to that of a constant gardener caring for an
      unhealthy tree, watering the leaves ("train the brain") or simply the roots
      ("mind the vessel"). The therapeutic difference probably consists in the amount
      and quality of water added to the tree, rather than by where one pours it, with
      either a top-down (leaves to roots) or bottom-up (roots to leaves) approach. 

PMID- 24856806
TI  - Impact of two different cardiac work-up strategies in patients undergoing
      abdominal aortic aneurysm repair.

PMID- 24856807
TI  - One-year clinical impact of cardiac arrest in patients with first onset acute ST
      segment elevation myocardial infarction.
AB  - BACKGROUND: Cardiac arrest complicating acute ST elevation myocardial infarction
      (STEMI) is known to be associated with increased in-hospital mortality. However,
      little is known about the long-term outcomes after cardiac arrest complicating
      first onset STEMI in contemporary percutaneous coronary intervention (PCI) era.
      METHODS: We analyzed 7942 consecutive patients who were diagnosed with STEMI and
      had no previous history of MI. They were divided into two groups according to the
      presence of cardiac arrest (group I, patients with cardiac arrest; n=481, group
      II, patients without cardiac arrest; n=7641). RESULTS: In a stepwise multivariate
      model, previous history of chronic kidney disease, high serum level of glucose
      and low high density lipoprotein-cholesterol was an independent predictor of
      cardiac arrest complicating STEMI. Group I had significantly higher in-hospital
      mortality (adjusted hazard ratio [HR] 3.06, 95% confidence interval [CI] 2.08
      4.51, p<0.001) and 30-day mortality after hospital discharge (adjusted HR 2.92,
      95% CI 1.86-4.58, log-rank p<0.001). However, there was no significant increase
      in mortality beyond 30 days (6-month, adjusted HR 1.46, 95% CI 0.45-4.77, log
      rank p=0.382; 1-year, adjusted HR 1.84, 95% CI 0.83-4.05, log-rank p=0.107).
      Also, there were no significant differences in 6-month and 1-year major adverse
      cardiac events in 30-day survivors. Performing PCI was associated with decreased
      12-month mortality in 30-day survivors. CONCLUSIONS: Although patients with
      cardiac arrest complicating first onset STEMI had higher in-hospital and 30-day
      mortality after hospital discharge, cardiac arrest itself did not have any
      residual impact on mortality as well as clinical outcomes.

PMID- 24856809
TI  - Gymnemic acids inhibit sodium-dependent glucose transporter 1.
AB  - To evaluate the activity of botanicals used in Chinese Traditional Medicine as
      hypoglycemic agents for diabetes type II prevention and/or treatment, extracts
      prepared from 26 medicinal herbs were screened for their inhibitory activity on
      sodium-dependent glucose transporter 1 (SGLT1) by using two-electrode voltage
      clamp recording of glucose uptake in Xenopus laevis oocytes microinjected with
      cRNA for SGLT1. Showing by far the strongest SGLT1 inhibitory effect, the
      phytochemicals extracted from Gymnema sylvestre (Retz.) Schult were located by
      means of activity-guided fractionation and identified as 3-O-beta-D
      glucuronopyranosyl-21-O-2-tigloyl-22-O-2-tigloyl gymnemagenin (1) and 3-O-beta-D
      glucuronopyranosyl-21-O-2-methylbutyryl-22-O-2-tigloyl gymnemagenin (2) by means
      of LC-MS/MS, UPLC-TOF/MS, and 1D/2D-NMR experiments. Both saponins exhibited low
      IC50 values of 5.97 (1) and 0.17 MUM (2), the latter of which was in the same
      range as found for the high-affinity inhibitor phlorizin (0.21 MUM). As SGLT1 is
      found in high levels in brush-border membranes of intestinal epithelial cells,
      these findings demonstrate for the first time the potential of these saponins for
      inhibiting electrogenic glucose uptake in the gastrointestinal tract.

PMID- 24856810
TI  - Clinicopathological correlates of Gli1 expression in a population-based cohort of
      patients with newly diagnosed bladder cancer.
AB  - INTRODUCTION: Dysregulation of the hedgehog signaling pathway has been linked to
      the development and progression of a variety of different human tumors including
      cancers of the skin, brain, colon, prostate, blood, and pancreas. We assessed the
      clinicopathological factors that are potentially related to expression of Gli1,
      the transcription factor that is thought to be the most reliable marker of
      hedgehog pathway activation in bladder cancer. METHODS: Bladder cancer cases were
      identified from the New Hampshire State Cancer Registry as histologically
      confirmed primary bladder cancer diagnosed between January 1, 2002, and July 31,
      2004. Immunohistochemical analysis was performed on a tissue microarray to detect
      Gli1 and p53 expression in these bladder tumors. We computed odds ratios (ORs)
      and their 95% CIs for Gli1 positivity for pathological category using T category
      (from TNM), invasiveness, and grade with both the World Health Organization 1973
      and World Health Organization International Society of Urological Pathology
      criteria. We calculated hazard ratios and their 95% CI for Gli1 positivity and
      recurrence for both Ta-category and invasive bladder tumors (T1+). RESULTS: A
      total of 194 men and 67 women, whose tumors were assessable for Gli1 staining,
      were included in the study. No appreciable differences in Gli1 staining were
      noted by sex, age, smoking status, or high-risk occupation. Ta-category tumors
      were more likely to stain for Gli1 as compared with T1-category tumors (adjusted
      OR = 0.38, CI: 0.17-0.87). Similarly, low-grade (grades 1-2) tumors were more
      likely to stain for Gli1 as compared with high-grade tumors (grade 3) (adjusted
      OR = 0.44, CI: 0.21-0.93). In a Cox proportional hazards regression analysis, non
      muscle-invasive bladder tumors expressing Gli1 were less likely to recur
      (adjusted hazard ratio = 0.48; CI: 0.28-0.82; P<0.05) than those in which Gli1
      was absent. CONCLUSION: Our findings indicate that Gli1 expression may be a
      marker of low-stage, low-grade bladder tumors and an indicator of a reduced risk
      of recurrence in this group.

PMID- 24856811
TI  - Significant immunohistochemical expression of human chorionic gonadotropin in
      high-grade osteosarcoma is rare, but may be associated with clinically elevated
      serum levels.
AB  - Survival rates have plateaued at 70% for osteosarcoma. Proteins ectopically
      produced by malignant tumors may provide insight into new therapeutic targets.
      Osteosarcomas secreting human chorionic gonadotropin (hCG) have been suggested to
      have a worse prognosis. We examined the frequency of expression of beta-subunit
      of hCG (beta-hCG) in pretreatment osteosarcoma biopsies, and asked if it was
      associated with various clinical prognostic parameters, and the development of
      metastases. We subjected 51 pretreatment biopsies of high-grade osteosarcoma,
      from 51 patients, to beta-hCG immunohistochemistry. In 19 of these patients,
      postchemotherapy metastatic biopsies also were examined for beta-hCG expression.
      Clinical information (patient age, sex, survival status, and serum hCG in females
      only), and tumor characteristics (site, size, and presence of metastases) were
      recorded. The beta-hCG positive and negative biopsies were separated and
      compared. Of 49 interpretable pretreatment biopsies, 28 (57%) showed positive
      cytoplasmic beta-hCG expression: 27 with sparse positivity (1% of tumor cells)
      and 1 with frequent positivity (10% of tumor cells). The patient with frequent
      beta-hCG positivity in her pretreatment biopsy had elevated serum hCG (88.2
      mIU/mL) at diagnosis, decreasing to undetectable following chemotherapy and
      definitive resection. There was no difference in clinical parameters or rate of
      metastasis between beta-hCG positive versus negative groups. Expression of beta
      hCG may be seen in high-grade osteosarcoma, but frequent beta-hCG
      immunohistochemical expression by tumor cells, associated with clinically
      elevated serum beta-hCG, is rare. Recognition that some nongerm cell tumors may
      produce beta-hCG can prevent confusion with malignancies containing neoplastic
      syncytiotrophoblast cells, including germ cell and trophoblastic tumors.

PMID- 24856812
TI  - Metal-porphyrin: a potential catalyst for direct decomposition of N(2)O by
      theoretical reaction mechanism investigation.
AB  - The adsorption of nitrous oxide (N2O) on metal-porphyrins (metal: Ti, Cr, Fe, Co,
      Ni, Cu, or Zn) has been theoretically investigated using density functional
      theory with the M06L functional to explore their use as potential catalysts for
      the direct decomposition of N2O. Among these metal-porphyrins, Ti-porphyrin is
      the most active for N2O adsorption in the triplet ground state with the strongest
      adsorption energy (-13.32 kcal/mol). Ti-porphyrin was then assessed for the
      direct decomposition of N2O. For the overall reaction mechanism of three N2O
      molecules on Ti-porphyrin, two plausible catalytic cycles are proposed. Cycle 1
      involves the consecutive decomposition of the first two N2O molecules, while
      cycle 2 is the decomposition of the third N2O molecule. For cycle 1, the
      activation energies of the first and second N2O decompositions are computed to be
      3.77 and 49.99 kcal/mol, respectively. The activation energy for the third N2O
      decomposition in cycle 2 is 47.79 kcal/mol, which is slightly lower than that of
      the second activation energy of the first cycle. O2 molecules are released in
      cycles 1 and 2 as the products of the reaction, which requires endothermic
      energies of 102.96 and 3.63 kcal/mol, respectively. Therefore, the O2 desorption
      is mainly released in catalytic cycle 2 of a TiO3-porphyrin intermediate
      catalyst. In conclusion, regarding the O2 desorption step for the direct
      decomposition of N2O, the findings would be very useful to guide the search for
      potential N2O decomposition catalysts in new directions. 

PMID- 24856818
TI  - Measuring the design of empathetic buildings: a review of universal design
      evaluation methods.
AB  - PURPOSE: Universal design (UD) provides an explanation of good design based on
      the user perspective, which are outlined through its principles, goals, and
      related frameworks. The aim of this paper is to provide an overview of the
      frameworks and methods for UD building evaluations and to describe how close they
      have come to describing what a universally designed building is. METHODS:
      Evaluation approaches are reviewed from the existing literature across a number
      of spatial disciplines, including UD, human geography and urban studies. RESULTS:
      Four categories of UD evaluation methods are outlined, including (1) checklist
      evaluations, (2) value-driven evaluations, (3) holistic evaluations, and (4)
      invisible evaluations. CONCLUSIONS: A number of suggestions are made to aid
      research aimed at developing UD evaluation in buildings. (1) Design standards and
      guidelines should be contested or validated where possible; (2) evaluation
      criteria should be contextual; (3) it may be more practical to have separate
      methodologies for contextualising UD to allow for the creation of an evaluating
      tool that is practical in use. Additionally, there is a difficulty in
      establishing a clear basis for evaluating how empathetic buildings are without
      expanding the methodological horizons of UD evaluation. Implications for
      Rehabilitation For universal design (UD) evaluation to address human need
      requires methods that are culturally, temporally, and typologically specific.
      Practical instruments for measuring UD need to be divorced from but contingent
      upon methods than can address local specificities. The process of evaluation can
      provide knowledge that can contest or validate the literature based sources such
      as design guidelines, or standards. UD evaluation requires constant renewal by
      searching for new, flexible strategies that can respond to socio-cultural change.

PMID- 24856819
TI  - HIV and cannot see.
AB  - A 55-year-old HIV-positive man presented with acute vision loss in the right eye
      and altered mental status. Ophthalmic evaluation revealed light perception vision
      OD with a right relative afferent pupillary defect, conjunctival chemosis, large
      mutton-fat keratitic precipitates, and diffuse cream-colored vitreous cells.
      Magnetic resonance imaging of the brain and orbit with and without contrast with
      fat saturation showed choroidal thickening OD, multifocal deep periventricular
      and deep ganglionic enhancing lesions, and a suprasellar mass. Brain biopsy
      showed diffuse large B-cell lymphoma. Intrathecal chemotherapy with methotrexate
      and cytarabine and whole brain radiation therapy failed. His mental status
      deteriorated. He developed pancytopenia, neutropenic fever, and septic shock and
      subsequently expired under palliative care. 

PMID- 24856820
TI  - Direct observations of amyloid beta self-assembly in live cells provide insights
      into differences in the kinetics of Abeta(1-40) and Abeta(1-42) aggregation.
AB  - Insight into how amyloid beta (Abeta) aggregation occurs in vivo is vital for
      understanding the molecular pathways that underlie Alzheimer's disease and
      requires new techniques that provide detailed kinetic and mechanistic
      information. Using noninvasive fluorescence lifetime recordings, we imaged the
      formation of Abeta(1-40) and Abeta(1-42) aggregates in live cells. For both
      peptides, the cellular uptake via endocytosis is rapid and spontaneous. They are
      then retained in lysosomes, where their accumulation leads to aggregation. The
      kinetics of Abeta(1-42) aggregation are considerably faster than those of Abeta(1
      40) and, unlike those of the latter peptide, show no detectable lag phase. We
      used superresolution fluorescence imaging to examine the resulting aggregates and
      could observe compact amyloid structures, likely because of spatial confinement
      within cellular compartments. Taken together, these findings provide clues as to
      how Abeta aggregation may occur within neurons. 

PMID- 24856821
TI  - One-pot synthesis of azoline-containing peptides in a cell-free translation
      system integrated with a posttranslational cyclodehydratase.
AB  - Azoline moieties in the backbones of peptidic natural products are important
      structural motifs that contribute to diverse bioactivities. Some azoline
      containing peptides (Az-peptides) are produced from ribosomally synthesized
      precursor peptides, in which cysteine, serine, and threonine residues are
      converted to their corresponding azolines by posttranslational modification
      through a cyclodehydratase. We have devised an in vitro biosynthesis system of Az
      peptides, referred to as the FIT-PatD (flexible in vitro translation) system, by
      the integration of a cell-free translation system with the posttranslational
      cyclodehydratase PatD. This system enabled the "one-pot" synthesis of a wide
      variety of Az-peptide derivatives expressed from synthetic DNA templates. The FIT
      PatD system also facilitated mutagenesis studies on a wide array of precursor
      peptide sequences, unveiling unique in vitro substrate tolerance of PatD. 

PMID- 24856823
TI  - Sudden collapses in the heat in patients on angiotensin type 2 receptor blockers.
AB  - CONTEXT: A clinical case report is presented of some patients taking angiotensin
      type 2 receptor blockers (AT2RB) who collapsed without warning whilst being
      active outdoors in the heat. ISSUES: It is not possible to recognise hypotension
      due to the heat by testing in a controlled environment such as a doctor's office.
      Many people taking AT2RBs may be thus misdiagnosed and inappropriately treated.
      LESSONS LEARNED: Sudden collapse in a patient on AT2RB who is active in the heat
      should alert the physician to the possible cause of extreme sensitivity to low
      grade volume depletion.

PMID- 24856822
TI  - Defining estrogenic mechanisms of bisphenol A analogs through high throughput
      microscopy-based contextual assays.
AB  - Environmental exposures to chemically heterogeneous endocrine-disrupting
      chemicals (EDCs) mimic or interfere with hormone actions and negatively affect
      human health. Despite public interest and the prevalence of EDCs in the
      environment, methods to mechanistically classify these diverse chemicals in a
      high throughput (HT) manner have not been actively explored. Here, we describe
      the use of multiparametric, HT microscopy-based platforms to examine how a
      prototypical EDC, bisphenol A (BPA), and 18 poorly studied BPA analogs (BPXs),
      affect estrogen receptor (ER). We show that short exposure to BPA and most BPXs
      induces ERalpha and/or ERbeta loading to DNA changing target gene transcription.
      Many BPXs exhibit higher affinity for ERbeta and act as ERbeta antagonists, while
      they act largely as agonists or mixed agonists and antagonists on ERalpha.
      Finally, despite binding to ERs, some BPXs exhibit lower levels of activity. Our
      comprehensive view of BPXs activities allows their classification and the
      evaluation of potential harmful effects. The strategy described here used on a
      large-scale basis likely offers a faster, more cost-effective way to identify
      safer BPA alternatives. 

PMID- 24856824
TI  - Chain-length and temperature dependence of self-assembled monolayers of
      alkylthiolates on Au(111) and Ag(111) surfaces.
AB  - We present a molecular dynamics (MD) study on the structure of self-assembled
      monolayers (SAMs) of alkylthiolates on various metal surfaces, with especial
      attention to Au(111) and Ag(111). Variations in the structure of these SAMs as a
      function of temperature and alkyl-chain length are systematically investigated.
      The MD simulations are performed by using a recently developed force field based
      on second-order Moller-Plesset perturbation theory calculations. Good agreement
      between the present results and the existing experimental data is found on
      Au(111). On Ag(111) the comparison between theory and experiment is also
      satisfactory for alkylthiolates with no more than 14 carbon atoms. The
      dependences of the average tilt angle of SAMs on temperature and chain length are
      easily understood by means of a simple single-chain model. 

PMID- 24856825
TI  - Human anti-peptidoglycan-IgG-mediated opsonophagocytosis is controlled by calcium
      mobilization in phorbol myristate acetate-treated U937 cells.
AB  - Recently, we demonstrated that human serum amyloid P component (SAP) specifically
      recognizes exposed bacterial peptidoglycan (PGN) of wall teichoic acid (WTA)
      deficient Staphylococcus aureus DeltatagO mutant cells and then induces
      complement-independent phagocytosis. In our preliminary experiments, we found the
      existence of human serum immunoglobulins that recognize S. aureus PGN (anti
      PGNIgGs), which may be involved in complement-dependent opsonophagocytosis
      against infected S. aureus cells. We assumed that purified serum anti-PGN-IgGs
      and S. aureus DeltatagO mutant cells are good tools to study the molecular
      mechanism of anti-PGN-IgG-mediated phagocytosis. Therefore, we tried to identify
      the intracellular molecule(s) that is involved in the anti-PGN-IgG-mediated
      phagocytosis using purified human serum anti-PGN-IgGs and different S. aureus
      mutant cells. Here, we show that anti-PGN-IgG-mediated phagocytosis in phorbol
      myristate acetate-treated U937 cells is mediated by Ca2(+) release from
      intracellular Ca2(+) stores and anti-PGN-IgG dependent Ca2(+) mobilization is
      controlled via a phospholipase Cgamma-2-mediated pathway.

PMID- 24856826
TI  - Evaluation of antimicrobial effects of commercial mouthwashes utilized in South
      Korea.
AB  - Streptococcus mutans is frequently associated with dental caries. Bacterial
      fermentation of food debris generates an acidic environment on the tooth surface,
      ultimately resulting in tooth deterioration. Therefore, various mouthwashes have
      been used to reduce and prevent Streptococcus mutans. The aim of this study was
      to evaluate the antimicrobial activities of 4 commercial mouthwashes and those of
      10% and 20% ethanol solutions (formula A, B, C, D, E and F) against Streptococcus
      mutans using biofilm and planktonic methods. The range of reduction in the viable
      cell count of Streptococcus mutans as estimated by the biofilm and planktonic
      methods was 0.05-5.51 log (P <= 0.01) and 1.23-7.51 log (P <= 0.001) compared
      with the negative control, respectively, indicating that the planktonic method
      had a stronger antibacterial effect against S. mutans. Among the tested
      formulations, formula A (Garglin regular(r) mouthwash) was the most effective
      against Streptococcus mutans (P <= 0.001).

PMID- 24856827
TI  - Zinc finger and BTB domain-containing protein 3 is essential for the growth of
      cancer cells.
AB  - ZBTB3 belongs to the Zinc finger and BTB/POZ domain containing transcription
      factor family; however, its biological role has rarely been studied. We
      demonstrate for the first time, to our knowledge, that ZBTB3 is an essential
      factor for cancer cell growth via the regulation of the ROS detoxification
      pathway. Suppression of ZBTB3 using two different short hairpin RNAs in human
      melanoma, lung carcinoma, and breast carcinoma results in diminished cell growth.
      In addition, we found that suppression of ZBTB3 activates a caspase cascade,
      including caspase-9, -3, and PARP leading to cellular apoptosis, resulting from
      failed ROS detoxification. We identified that ZBTB3 plays an important role in
      the gene expression of ROS detoxification enzymes. Our results reveal that ZBTB3
      may play a critical role in cancer cell growth via the ROS detoxification system.
      Therefore, therapeutic strategies that target ZBTB3 could be used in selective
      cancer treatments.

PMID- 24856828
TI  - Neuroprotective roles of pituitary adenylate cyclase-activating polypeptide in
      neurodegenerative diseases.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) is a pleiotropic
      bioactive peptide that was first isolated from an ovine hypothalamus in 1989.
      PACAP belongs to the secretin/glucagon/vasoactive intestinal polypeptide (VIP)
      superfamily. PACAP is widely distributed in the central and peripheral nervous
      systems and acts as a neurotransmitter, neuromodulator, and neurotrophic factor
      via three major receptors (PAC1, VPAC1, and VPAC2). Recent studies have shown a
      neuroprotective role of PACAP using in vitro and in vivo models. In this review,
      we briefly summarize the current findings on the neurotrophic and neuroprotective
      effects of PACAP in different brain injury models, such as cerebral ischemia,
      Parkinson's disease (PD), and Alzheimer's disease (AD). This review will provide
      information for the future development of therapeutic strategies in treatment of
      these neurodegenerative diseases.

PMID- 24856829
TI  - Phosphoinositide turnover in Toll-like receptor signaling and trafficking.
AB  - Lipid components in biological membranes are essential for maintaining cellular
      function. Phosphoinositides, the phosphorylated derivatives of
      phosphatidylinositol (PI), regulate many critical cell processes involving
      membrane signaling, trafficking, and reorganization. Multiple metabolic pathways
      including phosphoinositide kinases and phosphatases and phospholipases tightly
      control spatio-temporal concentration of membrane phosphoinositides. Metabolizing
      enzymes responsible for PI 4,5-bisphosphate (PI(4,5)P2) production or degradation
      play a regulatory role in Toll-like receptor (TLR) signaling and trafficking.
      These enzymes include PI 4-phosphate 5-kinase, phosphatase and tensin homolog, PI
      3-kinase, and phospholipase C. PI(4,5)P2 mediates the interaction with target
      cytosolic proteins to induce their membrane translocation, regulate vesicular
      trafficking, and serve as a precursor for other signaling lipids. TLR activation
      is important for the innate immune response and is implicated in diverse
      pathophysiological disorders. TLR signaling is controlled by specific
      interactions with distinct signaling and sorting adaptors. Importantly, TLR
      signaling machinery is differentially formed depending on a specific membrane
      compartment during signaling cascades. Although detailed mechanisms remain to be
      fully clarified, phosphoinositide metabolism is promising for a better
      understanding of such spatio-temporal regulation of TLR signaling and
      trafficking.

PMID- 24856830
TI  - Cohesin gene mutations in tumorigenesis: from discovery to clinical significance.
AB  - Cohesin is a multi-protein complex composed of four core subunits (SMC1A, SMC3,
      RAD21, and either STAG1 or STAG2) that is responsible for the cohesion of sister
      chromatids following DNA replication until its cleavage during mitosis thereby
      enabling faithful segregation of sister chromatids into two daughter cells.
      Recent cancer genomics analyses have discovered a high frequency of somatic
      mutations in the genes encoding the core cohesin subunits as well as cohesin
      regulatory factors (e.g. NIPBL, PDS5B, ESPL1) in a select subset of human tumors
      including glioblastoma, Ewing sarcoma, urothelial carcinoma, acute myeloid
      leukemia, and acute megakaryoblastic leukemia. Herein we review these studies
      including discussion of the functional significance of cohesin inactivation in
      tumorigenesis and potential therapeutic mechanisms to selectively target cancers
      harboring cohesin mutations.

PMID- 24856831
TI  - Enhancement of potency and stability of human extracellular superoxide dismutase.
AB  - Cells express several antioxidant enzymes to scavenge reactive oxygen species
      (ROS) responsible for oxidative damages and various human diseases. Therefore,
      antioxidant enzymes are considered biomedicine candidates. Among them,
      extracellular superoxide dismutase (SOD3) had showed prominent efficacy against
      asthma and inflammation. Despite its advantages as a biomedicine, the difficulty
      in obtaining large quantity of active recombinant human SOD3 (rhSOD3) has limited
      its clinical applications. We found that a significant fraction of overexpressed
      rhSOD3 was composed of the inactive apo-enzyme and its potency against
      inflammation depended on the rate of metal incorporation. Also, purified rhSOD3
      was unstable and lost its activity very quickly. Here, we suggest an ideal
      preparative method to express, purify, and store highly active rhSOD3. The
      enzymatic activity of rhSOD3 was maximized by incorporating metal ions into
      rhSOD3 after purification. Also, albumin or polyethylene glycol prevented rapid
      inactivation or degradation of rhSOD3 during preparative procedures and long-term
      storage.

PMID- 24856832
TI  - MicroRNA-directed cleavage of targets: mechanism and experimental approaches.
AB  - MicroRNAs (miRNAs) are a large family of post-transcriptional regulators, which
      are 21-24 nt in length and play a role in a wide variety of biological processes
      in eukaryotes. The past few years have seen rapid progress in our understanding
      of miRNA biogenesis and the mechanism of action, which commonly entails a
      combination of target degradation and translational repression. The target
      degradation mediated by Argonaute-catalyzed endonucleolytic cleavage exerts a
      significant repressive effect on target mRNA expression, particularly during
      rapid developmental transitions. This review outlines the current understanding
      of the mechanistic aspects of this important process and discusses several
      different experimental approaches to identify miRNA cleavage targets.

PMID- 24856833
TI  - Structure-activity relationship studies of indole-based compounds as small
      molecule HIV-1 fusion inhibitors targeting glycoprotein 41.
AB  - We previously described indole-containing compounds with the potential to inhibit
      HIV-1 fusion by targeting the hydrophobic pocket of transmembrane glycoprotein
      gp41. Here we report optimization and structure-activity relationship studies on
      the basic scaffold, defining the role of shape, contact surface area, and
      molecular properties. Thirty new compounds were evaluated in binding, cell-cell
      fusion, and viral replication assays. Below a 1 MUM threshold, correlation
      between binding and biological activity was diminished, indicating an amphipathic
      requirement for activity in cells. The most active inhibitor 6j exhibited 0.6 MUM
      binding affinity and 0.2 MUM EC50 against cell-cell fusion and live virus
      replication and was active against T20 resistant strains. Twenty-two compounds
      with the same connectivity displayed a consensus pose in docking calculations,
      with rank order matching the biological activity. The work provides insight into
      requirements for small molecule inhibition of HIV-1 fusion and demonstrates a
      potent low molecular weight fusion inhibitor. 

PMID- 24856834
TI  - Characterization of sex-based differences in the mechanical properties of human
      finger glabrous tissue using a fiberoptic sensor.
AB  - TAC-Cell is a custom-built somatosensory stimulator that delivers pneumatic
      cutaneous tactile inputs to virtually any skin target on the body and by virtue
      of its non-ferrous materials is compatible with functional magnetic resonance
      imaging (fMRI) and magnetoencephalography (MEG) brain scanners. In this study, we
      describe the method to measure apparent skin displacement induced by TAC-Cell
      stimulation of the glabrous surface of the distal phalanx of the index finger.
      Specifically, we studied the effect of four servo controller input voltages (0.4V
      1.0 V) on resultant skin displacement among eighteen, neurotypical adult male and
      female participants. A fiberoptic displacement sensor, commonly used in
      industrial applications, was coupled to the TAC-Cell to measure the glabrous
      skin's kinematic response to different stimulus amplitudes. Skin displacement was
      significantly dependent on stimulus amplitudes and sex (p<0.0001). Power spectrum
      and kinematic analysis of skin displacement showed that the pneumatic TAC-Cell
      stimulus consists of a spectrally rich, high velocity signal. In related work, we
      have shown that this dynamic pneumocutaneous stimulus is highly effective in
      evoking a cortical brain response for neurodiagnostic applications and
      somatosensory pathway analysis in health and disease.

PMID- 24856835
TI  - Modeling the role of IGF-1 on extracellular matrix biosynthesis and cellularity
      in intervertebral disc.
AB  - The insulin-like growth factor-1 (IGF-1) is a well-known anabolic agent for
      intervertebral disc (IVD), promoting both proteoglycan (PG) biosynthesis and cell
      proliferation. Accordingly, it is believed that IGF-1 may play a central role in
      IVD homeostasis. Furthermore, the exogenous administration of IGF-1 has been
      proposed as a possible therapeutic strategy for disc degeneration. The objectives
      of this study were to develop a new computational framework for describing the
      mechanisms regulating IGF-mediated homeostasis in IVD, and to apply this
      numerical tool for investigating the effectiveness of exogenous administration of
      IGF-1 for curing disc degeneration. A diffusive-reactive model was developed for
      describing competitive binding of IGF-1 to its binding proteins and cell surface
      receptors, with the latter reaction initiating the intracellular signaling
      mechanism leading to PG production and cell proliferation. Because PG production
      increases cell metabolic rate, and cell proliferation increases nutritional
      demand, nutrients transport and metabolism were also included into the model, and
      co-regulated, together with IGF-1, IVD cellularity. The sustainability and the
      effectiveness of IGF-mediated anabolism were investigated for conditions of
      pathologically insufficient nutrient supply, and for the case of exogenous
      administration of IGF-1 to degenerated IVD. Results showed that pathological
      nutrients deprivation, by decreasing cellularity, caused a reduction of PG
      biosynthesis. Also, exogenous administration of IGF-1 was only beneficial in well
      nourished regions of IVD, and exacerbated cell mortality in malnourished regions.
      These findings remark the central role of nutrition in IVD health, and suggest
      that adequate nutritional supply is paramount for achieving a successful IGF
      based therapy for disc degeneration. 

PMID- 24856836
TI  - Tavaborole for the treatment of onychomycosis.
AB  - INTRODUCTION: Onychomycosis causes approximately one-half of all nail disorders
      and its prevalence has been steadily increasing. It is difficult to treat, partly
      due to the subungual location and the inability of both oral and topical
      antifungals to reach the site of infection. Published cure rates with oral drugs
      are < 50% and even lower with topical drugs. Pathogenic factors include the
      diversity of fungal organisms and the difficulty of drugs penetrating the nail
      plate. Tavaborole is a broad-spectrum oxaborole antifungal agent with low
      molecular weight, permitting optimal nail plate penetration. In vitro and ex vivo
      studies have demonstrated the superior nail-penetrating properties of tavaborole
      compared to existing topical antifungal medications approved for the treatment of
      onychomycosis. AREAS COVERED: The clinical characteristics and prevalence of
      onychomycosis, currently available treatments, and the chemistry, safety and
      pharmacokinetic properties of tavaborole for the treatment of onychomycosis.
      EXPERT OPINION: Tavaborole is a novel, topical antifungal pharmaceutical agent
      pending FDA approval for the treatment of toenail onychomycosis due to
      dermatophytes. Efficacy has been demonstrated by a clinical development program
      including in vitro data and two large Phase III trials that enrolled ~ 1200
      patients. When approved, tavaborole topical solution, 5% may become a safe and
      effective option for the treatment of onychomycosis.

PMID- 24856837
TI  - Cervical/thoracotomic/thoracoscopic approaches for H-type congenital tracheo
      esophageal fistula: a systematic review.
AB  - PURPOSE: Aim of this systematic review is to investigate the thoracic and
      cervical surgical approaches of H-type tracheo-esophageal fistula (TEF) according
      to the position of the fistula. METHODS: The PubMed database was searched for
      original studies on H-type TEF treatment published between 1977 and 2012.
      Manuscripts finally included were divided into open and thoracoscopic surgery
      groups. RESULTS: Seventeen studies were selected for open surgery group, and most
      of them agree on the importance of pre-operative diagnosis of the fistula by
      preliminary tracheoscopy. Right cervicotomy was used in 70 cases (76.9%), left
      cervicotomy in 12 (13.2%), and thoracotomy only in 9 (9.9%). Five studies were
      included in thoracoscopic group (6 patients). Indications for the surgical
      approach (cervical vs thoracic) according to the position of the TEF were clearly
      described in 10 manuscripts, and all stated differences in surgical technique
      details. Complications and mortality rates were not statistically correlated to
      the different surgical approaches. CONCLUSIONS: The evidence base in regard to
      the treatment of H-type fistula in children is poor and the skills and
      preferences of the surgeons guide the choice of the procedure. Surgical division
      of the fistula is curative, and the key to a successful repair is the pre
      operatively identification of the level of the fistula with tracheoscopy. Right
      cervicotomy seems to be the approach of choice in the majority of case, with the
      thoracic approach appropriate only for fistulae opening below T2. Further well
      designed prospective studies which take into account of selection and performance
      bias are strongly required.

PMID- 24856838
TI  - "A long-term analysis of auricular position in pediatric patients who underwent
      post-auricular approaches".

PMID- 24856839
TI  - Colorectal cancer imaging: past, present and future.

PMID- 24856840
TI  - [What drives Meibomian gland disease?].

PMID- 24856841
TI  - Comparison of lead and tin concentrations in air at a solder manufacturer from
      the closed-face 37-mm cassette with and without a custom cellulose-acetate
      cassette insert.
AB  - A polyvinyl chloride (PVC) cassette insert with PVC filter (ACCU-CAP) in a 37-mm
      closed-face cassette (CFC) was designed for gravimetric analysis. A customized
      version of the ACCU-CAP, also to be used in the CFC, was manufactured from an
      acid-digestible cellulose-acetate cassette insert joined to a mixed cellulose
      ester (MCE) filter for wet chemical analysis. The aim of this study was to
      compare metal particle concentrations as sampled by the customized insert (CI) in
      a CFC sampler with the traditional sampling method using only a MCE filter in the
      CFC. Thirty-nine personal and 13 area samples were taken using paired filter
      based CFC and the CI in CFC samplers at a solder manufacturing plant. The CI was
      removed from its CFC, and digested and analyzed as a whole. The MCE filter from
      the typical CFC was removed for analysis and then the interior of the cassette
      was wiped with Ghost Wipe for a separate analysis. The MCE filter only, Ghost
      Wipe, and CI were separately dissolved in heated nitric acid for ICP-MS analysis.
      Overall, the geometric mean concentration of the filter-only (FO) samples was
      considerably lower than that of the CI samples, by 53% for lead and 32% for tin.
      However, if the FO analysis was added to the corresponding Ghost Wipe analysis,
      i.e., filter+interior wipe (FW), the geometric mean concentrations of the FW
      results were similar to those of the CI results (by 113% for lead and 98% for
      tin). For both lead and tin the comparison of (log-transformed) metal
      concentrations between the FW and CI results showed no statistically significant
      difference (p-value = 0.3009 for lead and 0.800 for tin), while the comparison
      between the FO and CI results shows statistically significant differences (all p
      values < 0.05). In conclusion, incorporating the sampler internal non-filter
      deposits by wiping or use of an internal filter capsule gave higher results than
      analyzing only the filter. Close agreement between the two methods of including
      non-filter deposits is an indication of general equivalency. 

PMID- 24856842
TI  - Comparative evaluation of outcomes of endoscopic versus percutaneous drainage for
      symptomatic pancreatic pseudocysts.

PMID- 24856843
TI  - Response.

PMID- 24856844
TI  - Colon capsule endoscopy after incomplete colonoscopy: Is it really useful and
      consensual?

PMID- 24856845
TI  - The not so NICE classification.

PMID- 24856846
TI  - Response.

PMID- 24856847
TI  - Response:.

PMID- 24856848
TI  - Chewing gum and completion rate in small-bowel capsule endoscopy: meta-analyzing
      the data.

PMID- 24856849
TI  - Radiofrequency ablation of Barrett's esophagus with the channel RFA endoscopic
      catheter.

PMID- 24856850
TI  - Women's preferences for selective estrogen reuptake modulators: an investigation
      using protection motivation theory.
AB  - OBJECTIVE: Selective estrogen receptor modulators (SERMs) reduce breast cancer
      risk by 38%. However, uptake is low and the reasons are not well understood. This
      study applied protection motivation theory (PMT) to determine factors associated
      with intention to take SERMs. METHODS: Women at increased risk of breast cancer
      (N=107), recruited from two familial cancer clinics in Australia, completed a
      questionnaire containing measures of PMT constructs. Hierarchical multiple linear
      regression analysis was used to analyze the data. RESULTS: Forty-five percent of
      women said they would be likely or very likely to take SERMs in the future. PMT
      components accounted for 40% of variance in intention to take SERMs. Perceived
      vulnerability, severity and response efficacy appeared the most influential in
      women's decisions to take or not take SERMs. CONCLUSION: Many women are
      interested in SERMs as a risk management option. Accurate risk estimation and an
      understanding of the benefits of SERMs are critical to women's decision making.
      PRACTICE IMPLICATIONS: Health professionals need to explore women's perceptions
      of their risk and its consequences, as well as providing clear evidence-based
      information about the efficacy of SERMs. Exploring the source and strength of
      beliefs about SERMs may allow more effective, tailored counseling.

PMID- 24856851
TI  - Molecular pathology of malignant melanoma: changing the clinical practice
      paradigm toward a personalized approach.
AB  - Melanocytic proliferations are notoriously difficult lesions to evaluate
      histologically, even among experts, as there is a lack of objective, highly
      reproducible criteria, which can be broadly applied to the wide range of
      melanocytic lesions encountered in daily practice. These difficult diagnoses are
      undeniably further compounded by the substantial medicolegal risks of an
      "erroneous" diagnosis. Molecular information and classification of melanocytic
      lesions is already vast and constantly expanding. The application of molecular
      techniques for the diagnosis of benignity or malignancy is, at times, confusing
      and limits its utility if not used properly. In addition, current and future
      therapies will necessitate molecular classification of melanoma into one of
      several distinct subtypes for appropriate patient-specific therapy. An
      understanding of what different molecular markers can and cannot predict is of
      the utmost importance. We discuss both mutational analysis and chromosomal
      gains/losses to help clarify this continually developing and confusing facet of
      pathology. 

PMID- 24856852
TI  - New-onset pancytopenia: a diagnostic approach.

PMID- 24856853
TI  - Diagnostic utility of NCOA2 fluorescence in situ hybridization and Stat6
      immunohistochemistry staining for soft tissue angiofibroma and morphologically
      similar fibrovascular tumors.
AB  - Soft tissue angiofibroma (STA), a recently suggested new histologic entity, is a
      benign fibrovascular soft tissue tumor composed of bland spindle-shaped tumor
      cells with abundant collagenous to myxoid stroma and branching small vessels. The
      lesion has a characteristic AHRR-NCOA2 fusion gene derived from chromosomal
      translocation of t(5;8)(p15;q13). However, morphologically similar tumors
      containing abundant fibrovascular and myxoid stroma can complicate diagnosis. We
      designed an original DNA probe for detecting NCOA2 split signals on fluorescence
      in situ hybridization (FISH) and estimated its utility with 20 fibrovascular
      tumors: 4 each of STAs, solitary fibrous tumors (SFTs), and cellular
      angiofibromas and 3 each of low-grade myxofibrosarcomas, myxoid liposarcomas, and
      low-grade fibromyxoid sarcomas. We also performed FISH for 13q14 deletion and
      immunohistochemistry (IHC) staining for estrogen receptor, progesterone receptor,
      retinoblastoma protein, and MUC-4 expression. Furthermore, IHC for Stat6 was
      conducted in the 20 cases analyzed by FISH and in an additional 26 SFTs. We found
      moderate to strong nuclear Stat6 expression in all SFTs but no expression in the
      other tumors. Both estrogen receptor and progesterone receptor expressions were
      observed in STAs, SFTs, and cellular angiofibromas. Expression of retinoblastoma
      protein was found in less than 10% of cells in all tumor types except myxoid
      liposarcoma. The low-grade fibromyxoid sarcomas were strongly positive for MUC-4.
      All STAs showed NCOA2 split signals on FISH. All tumors, regardless of histologic
      type, had 13q14 deletion. The NCOA2 FISH technique is a practical method for
      confirming STA diagnosis. The combination of NCOA2 FISH and Stat6 IHC proved
      effective for the differential diagnosis of STA, even when using small biopsy
      specimens. 

PMID- 24856854
TI  - A Web-based self-management exercise and diet intervention for breast cancer
      survivors: pilot randomized controlled trial.
AB  - BACKGROUND: Regular exercise and dietary practices have been shown to affect the
      health-related quality of life (HRQOL) and survival of breast cancer patients.
      OBJECTIVE: The current study aimed to investigate whether the WSEDI was a
      feasible and primarily effective method for promoting exercise and dietary
      behaviours for breast cancer patients. DESIGN: A 12-week randomized, controlled
      trial. SETTING: Oncology outpatient treatment clinics at 3 university hospitals
      and 1 National Cancer Center in South Korea. PARTICIPANTS: Fifty-nine breast
      cancer patients who had received curative surgery and completed primary cancer
      treatment within 12 months prior to the study and who had been diagnosed with
      stage 0-III cancers within 2 years prior to the study were recruited. METHODS:
      Participants were randomly assigned to either the intervention group, which used
      a Web-based self-management exercise and diet intervention program incorporating
      transtheoretical model (TTM)-based strategies (n=29), or to the control group,
      which used a 50-page educational booklet on exercise and diet (n=28). The
      intervention efficacy was measured at the baseline and 12 weeks via a Web-based
      survey that addressed the promotion of exercise and consumption of 5 servings of
      fruits and vegetables (F&V) per day, dietary quality, HRQOL, anxiety, depression,
      fatigue, motivational readiness, and self-efficacy. RESULTS: The proportion of
      subjects who performed at least moderate-intensity aerobic exercise for at least
      150 min per week; ate 5 servings of F&V per day; and had overall improvements in
      dietary quality, physical functioning and appetite loss (HRQOL), fatigue, and
      motivational readiness was greater in the intervention group than in the control
      group. The self-efficacy with respect to exercise and F&V consumption was greater
      in the intervention group than in the control group. A Web-based program that
      targets changes in exercise and dietary behaviours might be effective for breast
      cancer survivors if the TTM theory has been used to inform the program strategy,
      although further research with a larger sample size is required to enable
      definitive conclusions.

PMID- 24856860
TI  - Musculoskeletal ultrasound in childhood.
AB  - Ultrasonography is one of the first line imaging modalities for the evaluation of
      musculoskeletal disorders in children. This article provides an overview of the
      most important pathologic entities in which ultrasonography significantly
      contributes to the diagnostic workup. 

PMID- 24856861
TI  - Anesthesiologists' ability in calculating weight-based concentrations for
      pediatric drug infusions: an observational study.
AB  - STUDY OBJECTIVES: To assess the ability of anesthesiologists to calculate weight
      specific drug concentrations for continuous drug administration in children, and
      to evaluate the acceptance of an inhouse-developed, computer-based application
      for calculating drug infusions for pediatric cardiac surgery. DESIGN:
      Observational study. SETTING: Anesthesiology department of a tertiary-care
      medical center in Israel. PARTICIPANTS: 45 anesthesiology department staff
      members (attendings and residents). MEASUREMENTS: Anesthesiologists were asked to
      calculate the weight-based amount of drug and the corresponding amount in mL to
      be drawn from a standard vial and added to a 50-mL syringe in order to reach an
      infusion rate, where 1 mL/hr corresponds to 1 MUg x kg(-1) x min(-1). The time it
      took to reach the result was measured. Staff members were also asked to rate the
      user-friendliness and usability of the program. MAIN RESULTS: 41 of the original
      42 participants returned the completed questionnaire. Only 6 (15%) of 41
      anesthesiologists provided all the correct answers. The mean calculation time
      required was 205 (+/-53) seconds. There was no difference in success rate between
      attendings and residents. Incorrect calculations ranged from a drug concentration
      50 times too low up to 56 times too high. Most staff members believed that the
      computer-based application to perform these calculations reduced errors (65%) and
      workload (81%), and improved patient treatment (71%). This application was rated
      as very user-friendly. CONCLUSIONS: Anesthesiologists have difficulty calculating
      pediatric drug concentrations for continuous drug infusions. The correct
      calculations are time-consuming. Incorrect calculations may lead to dangerously
      high or low doses. A computer-based application to calculate drug concentrations
      was rated as very useful and user-friendly.

PMID- 24856862
TI  - Differences in typing forces, muscle activity, comfort, and typing performance
      among virtual, notebook, and desktop keyboards.
AB  - The present study investigated whether there were physical exposure and typing
      productivity differences between a virtual keyboard with no tactile feedback and
      two conventional keyboards where key travel and tactile feedback are provided by
      mechanical switches under the keys. The key size and layout were same across all
      the keyboards. Typing forces; finger and shoulder muscle activity; self-reported
      comfort; and typing productivity were measured from 19 subjects while typing on a
      virtual (0 mm key travel), notebook (1.8 mm key travel), and desktop keyboard (4
      mm key travel). When typing on the virtual keyboard, subjects typed with less
      force (p's < 0.0001) and had lower finger flexor/extensor muscle activity (p's <
      0.05). However, the lower typing forces and finger muscle activity came at the
      expense of a 60% reduction in typing productivity (p < 0.0001), decreased self
      reported comfort (p's < 0.0001), and a trend indicating an increase in shoulder
      muscle activity (p's < 0.10). Therefore, for long typing sessions or when typing
      productivity is at a premium, conventional keyboards with tactile feedback may be
      more suitable interface. 

PMID- 24856863
TI  - [Cardiac disease at risk in the young athlete].
AB  - Physical training significantly reduces all cause mortality in the general
      population. Eligibility for competitive sport participation in athletes with
      cardiovascular diseases is based on recommendations. Incidence of sudden cardiac
      death in young athletes is low (0.5 to 2/100,000 athletes/year). The most common
      cardiac diseases at risk are hypertrophic cardiomyopathies, congenital coronary
      arteries abnormalities, arrhythmogenic right ventricular cardiomyopathy and acute
      myocarditis. Pre-participation screening is based on the cardiovascular
      evaluation, including ECG (repeated every 3years since the age of 12 and every
      5years since the age of 20 to the age of 35). Some events are unpredictable
      (idiopathic ventricular fibrillation, sudden death related to congenital coronary
      arteries abnormalities or commotio cordis). A better access to public
      defibrillation is needed. 

PMID- 24856864
TI  - Development and psychometric testing of inflammatory bowel disease fatigue (IBD
      F) patient self-assessment scale.
AB  - BACKGROUND AND AIMS: Fatigue is one of the main symptoms of inflammatory bowel
      disease (IBD) and is frequently reported by people in both active and quiescent
      disease. Many different fatigue assessment scales have been used to measure
      fatigue, but none has been developed or tested in IBD. This study aimed to
      develop a fatigue scale specific to the needs and experiences of people with IBD.
      METHODS: A five-step sequential mixed method design was used: a qualitative phase
      to assess patients' experience of fatigue and its impact on their lives, and four
      mixed qualitative-quantitative phases to refine the scale and to assess its
      psychometric properties. RESULTS: 567 people participated in five phases. The
      resulting questionnaire has 3 sections: 5 questions assessing frequency and
      severity of fatigue; 30 questions rating the experience and impact of fatigue;
      and a free-text section asking for patients' comments and additional issues
      related to fatigue. Initial validation suggests that the questionnaire has good
      face and content validity, acceptable to excellent test-retest stability (ICC
      0.74 for Section 1 and 0.83 for Section 2) and a high degree of internal
      consistency (Cronbach's alpha>0.9). CONCLUSIONS: Participants in the study
      confirmed that fatigue in IBD is burdensome. Items generated and refined by
      people with IBD-fatigue reflect their experience and form the basis of this new
      IBD-fatigue scale, which is psychometrically robust with reliability estimates
      which fall within statistically acceptable ranges. The scale can be used by
      patients and practitioners to assess severity and impact of fatigue in people
      with IBD.

PMID- 24856865
TI  - Relation of resistin, leptin and adiponectin--trinity of adipose tissue
      dysfunction assessment.

PMID- 24856866
TI  - Identification of Atlantic cod (Gadus morhua), ling (Molva molva), and Alaska
      pollock (Gadus chalcogrammus) by PCR-ELISA using duplex PCR.
AB  - Species-specific PCR-ELISA assays for the identification of Atlantic cod (Gadus
      morhua), Alaska pollock (Gadus chalcogrammus), and ling (Molva molva) in food
      products have been developed. The method, comprising a set of primers common to
      the first two species, a set of primers for M. molva, and a probe for each
      species, was designed using ND4 and cytochrome b genes as molecular markers. The
      sensitivity and selectivity were then determined for each assay. These assays
      were afterward used to analyze DNA extracted from commercial fish products. The
      presence of the target species was successfully detected in all analyzed samples,
      demonstrating the applicability of this method to the analysis of food products. 

PMID- 24856867
TI  - Prevalence and genotypes of extended spectrum beta-lactamases in
      Enterobacteriaceae isolated from human stool and chicken meat in Hamburg,
      Germany.
AB  - Chicken meat has been proposed to constitute a source for extended spectrum beta
      lactamase (ESBL)-carrying Enterobacteriaceae that colonize and infect humans. In
      this study the prevalence of ESBL-producing Enterobacteriaceae in stool samples
      from ambulatory patients who presented in the emergency department of the
      University Medical Centre Hamburg-Eppendorf with gastrointestinal complains and
      in chicken meat samples from the Hamburg region were analysed and compared with
      respect to ESBL-genotypes, sequence types and antibiotic resistance profiles.
      Twenty-nine (4.1%) of 707 stool samples and 72 (60%) of 120 chicken meat samples
      were positive for ESBL-producing Enterobacteriaceae. The distribution of ESBL
      genes in the stool vs. chicken meat isolates (given as % of total isolates from
      stool vs. chicken meat) was as follows: CTX-M-15 (38% vs. 0%), CTX-M-14 (17% vs.
      6%), CTX-M-1 (17% vs. 69%), SHV-12 (3% vs. 18%) and TEM-52 (3% each). Comparison
      of ESBL- and multilocus sequence type revealed no correlation between isolates of
      human and chicken. Furthermore, ESBL-producing E. coli from stool samples were
      significantly more resistant to fluoroquinolones, aminoglycosides and/or
      trimethoprim-sulfamethoxazole than chicken isolates. The differences in ESBL
      genotypes, sequence types and antibiotic resistance patterns indicate that in our
      clinical setting chicken meat is not a major contributor to human colonization
      with ESBL-carrying Enterobacteriaceae.

PMID- 24856868
TI  - Characterization of ferrocene-modified electrode using electrochemical surface
      forces apparatus.
AB  - A electrochemical surface forces apparatus (EC-SFA) was employed to measure the
      interactions between gold electrodes modified with self-assembled monolayers of
      ferrocene alkyl thiol (Fc-SAM) and oxidized ferrocene (ferrocenium cation, Fc(+)
      SAM) in a 1 mM aqueous electrolyte. The double-layer repulsion in both cases of
      the Fc-SAM and Fc(+)-SAM electrodes was observed. The surface charge density
      (sigma) evaluated from the double-layer repulsions between the Fc(+)-SAM
      electrodes in 1 mM aqueous KClO4 was 0.0027 C/m(2), which was 2.5 times greater
      than that of the Fc-SAM, at 0.0011 C/m(2). The sigma values of the Fc(+)-SAM were
      evaluated for various counteranions using the same method, which were 0.0048,
      0.0040, and 0.0104 C/m(2) for NO3(-), SO4(2-), and CF3SO3(-), respectively. The
      degrees of dissociation (alphad) between the ferrocenium cation and these
      counteranions were obtained from sigma and the density of the ferrocenium on the
      electrode. The alphad value of CF3SO3(-), 4.1%, was the highest, followed in the
      order, SO4(2-) > NO3(-) > ClO4(-), indicating that most of the positive charges
      of the ferrocenium cation were compensated by formation of an ion pair with
      counteranions. 

PMID- 24856869
TI  - Static magnetic field increases survival rate of dental pulp stem cells during
      DMSO-free cryopreservation.
AB  - Successful and efficient cryopreservation of living cells and organs is a key
      clinical application of regenerative medicine. Recently, magnetic
      cryopreservation has been reported for intact tooth banking and cryopreservation
      of dental tissue. The aim of this study was to assess the cryoprotective effects
      of static magnetic fields (SMFs) on human dental pulp stem cells (DPSCs) during
      cryopreservation. Human DPSCs isolated from extracted teeth were frozen with a
      0.4-T or 0.8-T SMF and then stored at -196  degrees C for 24 h. During freezing,
      the cells were suspended in freezing media containing with 0, 3 or 10% DMSO.
      After thawing, the changes in survival rate of the DPSCs were determined by flow
      cytometry. To understand the possible cryoprotective mechanisms of the SMF, the
      membrane fluidity of SMF-exposed DPSCs was tested. The results showed that when
      the freezing medium was DMSO-free, the survival rates of the thawed DPSCs
      increased 2- or 2.5-fold when the cells were exposed to 0.4-T or 0.8-T SMFs,
      respectively (p < 0.01). In addition, after exposure to the 0.4-T SMF, the
      fluorescence anisotropy of the DPSCs increased significantly (p < 0.01) in the
      hydrophilic region. These results show that SMF exposure improved DMSO-free
      cryopreservation. This phenomenon may be due to the improvement of membrane
      stability for resisting damage caused by ice crystals during the freezing
      procedure. 

PMID- 24856870
TI  - Microwave effect on diffusion: a possible mechanism for non-thermal effect.
AB  - In this study, we assume that microwave radiation affects hydrogen bonding
      between dipolar water molecules and through that diffusion in water at constant
      temperature. The experimental study was performed on the setup of two identical
      reservoirs filled with pure water and 0.9% NaCl solution and connected by a thin
      tube. Alterations of NaCl concentration in the reservoir initially filled with
      pure water were measured using the resistance of the solution as an indicator.
      The applied 450 MHz continuous-wave microwave field had the maximal specific
      absorption rate of 0.4 W/kg on the connecting tube. The standard deviation of
      water temperature in the setup was 0.02  degrees C during an experiment. Our
      experimental data demonstrated that microwave exposure makes faster the process
      of diffusion in water. The time required for reduction of initial resistance of
      the solution by 10% was 1.7 times shorter with microwave. This result is
      consistent with the proposed mechanism of low-level microwave effect: microwave
      radiation, rotating dipolar water molecules, causes high-frequency alterations of
      hydrogen bonds between water molecules, thereby affects its viscosity and makes
      faster diffusion. 

PMID- 24856871
TI  - Magnetic nano-Fe3O4 particles targeted gathering and bio-effects on nude mice
      loading human hepatoma Bel-7402 cell lines model under external magnetic field
      exposure in vivo.
AB  - Magnetic nano-Fe3O4 particles (MNPs), static magnetic field (SMF) and extremely
      low-frequency altering electric magnetic field (ELFF) were utilized to treat nude
      mice loading hepatoma Bel-7402 cell lines to investigate the therapeutic values
      of MNPs combined with ELFF in vivo. Magnetic resonance image (MRI) figures showed
      that about 98.9% MNPs injected into mice body through tail vein were gathered in
      tumor focal by SMF directing exposure. Single ELFF and MNPs treatments did not
      influence mice physiological function obviously. However, gathered MNPs combined
      with ELFF treatment prolonged mice survival time and inhibited loading tumor
      cells proliferation significantly compared to other mice groups (p < 0.05);
      furthermore, the tumor cells early apoptosis ratio of mice group was
      significantly higher than other groups (p < 0.05), and ELFF combined with
      gathered MNPs treatment improved tumor cells early apoptosis associated with Bcl
      group protein expression: Bax protein expression was higher than Bcl-2 and the
      combined treatment improved cells Heat shock protein-27 (Hsp-27) expression which
      could protect cells avoiding early apoptosis. The possible mechanism that this
      kind of combination inducing more cells into early apoptosis could be due to ELFF
      exposure influencing cells ion metabolism, MNPs strengthening the effects, and
      the ELFF vibrating MNPs to generate extra heat and activate cellular heat shock
      signal channel. 

PMID- 24856872
TI  - Biochemical parameters after cholecalciferol repletion in hemodialysis: results
      From the VitaDial randomized trial.
AB  - BACKGROUND: The 2009 KDIGO (Kidney Disease: Improving Global Outcomes) chronic
      kidney disease-mineral and bone disorder clinical practice guideline suggests
      correcting 25-hydroxyvitamin D3 (25[OH]D) levels<30ng/mL in patients treated with
      maintenance hemodialysis, but does not provide a specific treatment protocol.
      STUDY DESIGN: 2-center, double-blind, randomized, 13-week, controlled trial
      followed by a 26-week open-label study. SETTING & PARTICIPANTS: 55 adult
      maintenance hemodialysis patients with 25(OH)D levels<30ng/mL were recruited from
      June 2008 through October 2009. INTERVENTION: Cholecalciferol, 25,000IU, per week
      orally versus placebo for 13 weeks, then 26 weeks of individualized
      cholecalciferol prescription based on NKF-KDOQI (National Kidney Foundation
      Kidney Disease Outcomes Quality Initiative) guidelines. OUTCOMES: Primary end
      point was the percentage of patients with 25(OH)D levels>=30ng/mL at 13 weeks.
      Secondary outcomes included the percentage of patients with normal calcium,
      phosphorus, and intact parathyroid hormone (iPTH) blood levels. Safety measures
      included incidence of hypercalcemia and hypervitaminosis D. MEASUREMENTS: Blood
      calcium and phosphate were measured weekly; iPTH, 25(OH)D, 1,25-dihydroxyvitamin
      D3 (1,25[OH]2D), and bone turnover markers, trimonthly; fetuin A and fibroblast
      growth factor 23 (FGF-23) serum levels and aortic calcification scores were
      determined at weeks 0 and 39. RESULTS: The primary end point significantly
      increased in the treatment group compared with the placebo group (61.5% vs 7.4%;
      P<0.001), as well as 1,25(OH)2D levels (22.5 [IQR, 15-26] vs 11 [IQR, 10
      15]pg/mL; P<0.001) and the proportion of patients achieving the target calcium
      level (76.9% vs 48.2%; P=0.03). Incidence of hypercalcemia and phosphate and iPTH
      levels were similar between groups. The second 26-week study phase did not
      significantly modify the prevalence of 25(OH)D level>=30ng/mL in patients issued
      from the placebo group. LIMITATIONS: Small size of the study population.
      CONCLUSIONS: Oral weekly administration of 25,000IU of cholecalciferol for 13
      weeks is an effective, safe, inexpensive, and manageable way to increase 25(OH)D
      and 1,25(OH)2D levels in hemodialysis patients. Further evaluation of clinical
      end points is suggested.

PMID- 24856873
TI  - Diagnosis of trombiculosis by videodermatoscopy.

PMID- 24856874
TI  - Late-life depression and cardiovascular disease burden: examination of reciprocal
      relationship.
AB  - OBJECTIVES: Empirical studies of the relationship between depression and
      cardiovascular disease (CVD) tend to be limited to examination of one-way
      relationships. This study assessed both cross-sectional association and
      longitudinal reciprocal relationships between late-life depressive symptoms and
      CVD. METHODS: The National Health and Aging Trends Study waves 1 (T1) and 2 (T2,
      one year later) provided the data. The study sample (N = 5,414) represented
      Medicare beneficiaries aged 65 years or older. We fit structural equation models
      to examine: 1) cross-sectional association between depression and CVD at each
      wave; and 2) longitudinal reciprocal relationship between T1 depression and T2
      CVD and between T1 CVD and T2 depression. RESULTS: At T1, 28.6% reported a CVD
      diagnosis, and at T2, 4.9% reported having had a new diagnosis or new episode of
      heart attack or heart disease and 2.2% reported having had a stroke since T1. In
      addition to significant cross-sectional relationships between depression and CVD,
      T1 CVD had significant impact on T2 depressive symptoms, and T1 depressive
      symptoms had significant impact on T2 CVD, with a 1-point increase in depressive
      symptom score increasing the odds of having a new CVD diagnosis or episode by
      21%. CONCLUSIONS: The care of older adults with CVD and/or depression needs to
      include interventions focusing on lifestyle and psychological factors that can
      reduce risks for both CVD and depression. Depression prevention and treatment
      also needs to be an integral part of CVD prevention and management.

PMID- 24856875
TI  - Mechanomyography and muscle function assessment: a review of current state and
      prospects.
AB  - Previous studies have explored to saturation the efficacy of the conventional
      signal (such as electromyogram) for muscle function assessment and found its
      clinical impact limited. Increasing demand for reliable muscle function
      assessment modalities continues to prompt further investigation into other
      complementary alternatives. Application of mechanomyographic signal to quantify
      muscle performance has been proposed due to its inherent mechanical nature and
      ability to assess muscle function non-invasively while preserving muscular
      neurophysiologic information. Mechanomyogram is gaining accelerated applications
      in evaluating the properties of muscle under voluntary and evoked muscle
      contraction with prospects in clinical practices. As a complementary modality and
      the mechanical counterpart to electromyogram; mechanomyogram has gained
      significant acceptance in analysis of isometric and dynamic muscle actions.
      Substantial studies have also documented the effectiveness of mechanomyographic
      signal to assess muscle performance but none involved comprehensive appraisal of
      the state of the art applications with highlights on the future prospect and
      potential integration into the clinical practices. Motivated by the dearth of
      such critical review, we assessed the literature to investigate its principle of
      acquisition, current applications, challenges and future directions. Based on our
      findings, the importance of rigorous scientific and clinical validation of the
      signal is highlighted. It is also evident that as a robust complement to
      electromyogram, mechanomyographic signal may possess unprecedented potentials and
      further investigation will be enlightening. 

PMID- 24856876
TI  - Microwave-driven asbestos treatment and its scale-up for use after natural
      disasters.
AB  - Asbestos-containing debris generated by the tsunami after the Great East Japan
      Earthquake of March 11, 2011, was processed by microwave heating. The analysis of
      the treated samples employing thermo gravimetry, differential thermal analysis, X
      ray diffractometry, scanning electron microscopy, and phase-contrast microscopy
      revealed the rapid detoxification of the waste by conversion of the asbestos
      fibers to a nonfibrous glassy material. The detoxification by the microwave
      method occurred at a significantly lower processing temperature than the thermal
      methods actually established for the treatment of asbestos-containing waste. The
      lower treatment temperature is considered to be a consequence of the microwave
      penetration depth into the waste material and the increased intensity of the
      microwave electric field in the gaps between the asbestos fibers resulting in a
      rapid heating of the fibers inside the debris. A continuous treatment plant
      having a capacity of 2000 kg day(-1) of asbestos-containing waste was built in
      the area affected by the earthquake disaster. This treatment plant consists of a
      rotary kiln to burn the combustible waste (wood) and a microwave rotary kiln to
      treat asbestos-containing inorganic materials. The hot flue gas produced by the
      combustion of wood is introduced into the connected microwave rotary kiln to
      increase the energy efficiency of the combined process. Successful operation of
      this combined device with regard to asbestos decomposition is demonstrated. 

PMID- 24856878
TI  - Mycobacterium bovis in California dairies: a case series of 2002-2013 outbreaks.
AB  - From 2002 to 2013, bovine tuberculosis (bTB) caused by Mycobacterium bovis (M.
      bovis) has been detected on numerous dairies in California. In total, twelve
      herds had bTB detected and are included in the case series which describes these
      recent outbreaks and discusses potential pathways of introduction.
      Epidemiological investigations to determine the initial source of bTB in each
      herd included obtaining data on likely pathways of pathogen introduction.
      Pathways included purchasing cattle, use of heifer-raising operations,
      commingling of cattle at greater risk of exposure to infected cattle with cattle
      destined for California dairies, contact with infected wildlife, exposure to
      humans with bTB infections, community and neighboring herds and others.
      Epidemiologic and molecular typing data confirmed the source of infection in 3
      herds and probable sources of infection in 2 herds. In the 7 remaining herds
      described in this case series an epidemiologic link to a source could not be
      determined and molecular typing results did not associate M. bovis isolates
      acquired from these herds with another specific U.S. herd or U.S.-born animal.
      Preventing new introductions of M. bovis onto California dairies will require
      rigorous epidemiologic investigation of all the potential pathways of
      introduction discussed here. The root cause(s) of bTB on California dairies is
      certainly multifactorial with complex interactions of herd management practices,
      importation of cattle at greater risk of exposure to infected cattle, and the
      potential of human M. bovis exposure. The extensive use of molecular typing has
      improved epidemiologists' ability to narrow the scope of potential sources. 

PMID- 24856879
TI  - Postoperative Mycoplasma hominis infections after neurosurgical intervention.
AB  - OBJECT: Mycoplasma hominis is a rare cause of infection after neurosurgical
      procedures. The Mycoplasma genus contains the smallest bacteria discovered to
      date. Mycoplasma are atypical bacteria that lack a cell wall, a feature that
      complicates both diagnosis and treatment. The Gram stain and some types of
      culture media fail to identify these organisms, and typical broad-spectrum
      antibiotic regimens are ineffective because they act on cell wall metabolism.
      Mycoplasma hominis commonly colonizes the genitourinary tract in a nonvirulent
      manner, but it has caused postoperative, postpartum, and posttraumatic infections
      in various organ systems. The authors present the case of a 17-year-old male with
      a postoperative intramedullary spinal cord abscess due to M. hominis and report
      the results of a literature review of M. hominis infections after neurosurgical
      procedures. Attention is given to time to diagnosis, risk factors for infection,
      ineffective antibiotic regimens, and final effective antibiotic regimens to
      provide pertinent information for the practicing neurosurgeon to diagnose and
      treat this rare occurrence. METHODS: A PubMed search was performed to identify
      reports of M. hominis infections after neurosurgical procedures. RESULTS: Eleven
      cases of postneurosurgical M. hominis infection were found. No other cases of
      intramedullary spinal cord abscess were found. Initial antibiotic coverage was
      inadequate in all cases, and diagnosis was delayed in all cases. Multiple
      surgical interventions were often needed. Once appropriate antibiotics were
      started, patients typically experienced rapid resolution of their neurological
      symptoms. In 27% of cases, a suspicious genitourinary source other than urinary
      catheterization was identified. CONCLUSIONS: Postoperative M. hominis infections
      are rarely seen after neurosurgical procedures. They are typically responsive to
      appropriate antibiotic therapy. Mycoplasma infection may cause prolonged
      hospitalization and multiple returns to the operating room due to delay in
      diagnosis. Early clinical suspicion with appropriate antibiotic coverage could
      help prevent these significant complications.

PMID- 24856880
TI  - Letter to the Editor: cerebrospinal fluid puncture in myelomeningocele patients.

PMID- 24856881
TI  - Utility of computed tomography or magnetic resonance imaging evaluation of
      ventricular morphology in suspected cerebrospinal fluid shunt malfunction.
AB  - OBJECT: It is common to evaluate children with suspected CSF shunt malfunctions
      using CT of the head or, more recently, "quick brain" MRI. However, the
      reliability of using ventricular behavior, as assessed on cranial imaging during
      previous presentations with shunt obstructions, is not well defined. The authors
      conducted a study to determine if CT or MRI of ventricular morphology added
      useful clinical information in the evaluation of shunt malfunctions. METHODS: A
      retrospective chart review of children operated on at Texas Children's Hospital
      from February 20, 2011, to June 18, 2013, for shunt obstruction was conducted.
      Inclusion criteria involved age 3 years or older in patients who had undergone
      two or more shunt revisions for intraoperatively confirmed obstructions. Patients
      with shunt infection but without shunt obstruction and patients with fourth
      ventricular shunt failure were excluded from the study. Preoperative CT or MRI
      results were dichotomized into two distinct categories, as determined by a
      radiologist's report: either dilation of the ventricular system in comparison
      with prior scans at points the shunt was deemed functional, or no dilation of the
      ventricular system in comparison such scans. Determination of the presence of
      shunt obstruction was assessed by findings documented by the surgeon in the
      operative report. Each case was then analyzed to see if the patient has a
      reliable pattern of ventricular dilation, or no dilation, at times of shunt
      obstruction. RESULTS: Forty-two patients (25 males and 17 females) were included
      in the study. There were a total of 117 patient encounters analyzed and an
      average of 2.79 encounters per patient. The mean age at shunt failure
      presentation was 10.8 years (range 3-23 years). In 4 encounters, patients
      presented with a CSF leak or pseudomeningocele. Twenty-seven patients (64%)
      consistently demonstrated dilation of the ventricular system during episodes of
      shunt obstruction. Four patients (10%) consistently demonstrated no dilation
      during episodes of shunt obstruction. Eleven patients (26%) demonstrated
      inconsistent changes in ventricular size at times of shunt obstruction. In those
      first patient encounters with shunt obstruction presenting with ventricular
      dilation, 92% (49 of 53) of subsequent encounters demonstrated ventricular
      dilation with shunt obstruction presentations. CONCLUSIONS: Historical CT or MRI
      data regarding ventricular morphology patterns seen during prior examinations of
      shunt obstructions may inform a clinician's judgment of shunt obstruction on
      subsequent presentations, but they are not conclusive. In the present series, the
      authors found that changes in the morphology of a given patient's ventricular
      system when shunt obstruction occurs were often consistent and predictable, but
      not always. It remains imperative, however, that cranial images obtained to rule
      out shunt malfunction be compared with prior studies.

PMID- 24856884
TI  - Skin testing only with penicillin G in children with a history of penicillin
      allergy.
AB  - BACKGROUND: The absence of commercially available penicilloyl-polylysine (PPL)
      for most of the last decade severely hampered the practice of penicillin allergy
      evaluation because skin testing without PPL is reported to have a poor negative
      predictive value (NPV). OBJECTIVE: To determine the safety and NPV of skin
      testing without PPL using only penicillin G followed by a 3-dose graded challenge
      to the incriminated penicillin in children with a history of penicillin allergy.
      METHODS: Patients evaluated for a history of penicillin allergy at the CHU Sainte
      Justine Allergy Clinic between December 2006 and December 2009 were skin tested
      only with penicillin G and underwent a 3-dose graded challenge to the culprit
      penicillin if the skin test result was negative. RESULTS: Among 563 patients skin
      tested to penicillin G, 185 (33%) had a positive skin test result. These patients
      had a shorter interval between the initial reaction and skin testing compared
      with patients with a negative skin test result (P = .03). A total of 375 of 378
      patients (99%) with a negative skin test result were challenged and 18 (4.8%)
      reacted, translating into a NPV of 95.2% (95% confidence interval [CI], 92.5%
      97.1%). Three of 17 patients with a history of anaphylaxis and a negative skin
      test result reacted to challenge (NPV, 82.4%; 95% CI, 59.0-93.8%). All challenge
      reactions were mild and resolved promptly with treatment. CONCLUSION: Among
      children with a history of penicillin allergy, skin testing only with penicillin
      G followed by a 3-dose graded challenge to the incriminated penicillin is safe
      and yields a good NPV. This approach could be useful when PPL is unavailable.

PMID- 24856885
TI  - Practice parameters and strength of recommendation data: a variable compass.
AB  - BACKGROUND: Practice parameters and guidelines shape and influence the method and
      manner in which medicine is practiced. With more than 121 scales and methods of
      assessing and rating evidence, a comparison of practice parameters can appear
      daunting. An evaluation of the evidence engenders a sense of the evolution of a
      specialty and a roadmap for the future. OBJECTIVE: To assess the level of
      evidence underlying recommendations in allergy-immunology (AI) practice
      parameters. METHODS: We analyzed the practice parameters that guide AI (n = 15),
      otolaryngology (n = 8), pediatrics (n = 13), and internal medicine (n = 10) as
      they appeared on August 30, 2012. Strength of recommendation data was compared
      after making adjustments for differences in rating scales. RESULTS: The strength
      of recommendation calculated from strong to weak for the AI practice parameters
      using a standardized format yielded the following grades: A in 195 (13.9%), B in
      342 (24.4%), C in 606 (43.2%), D in 231 (16.4%), and E in 29 (2.1%). Controlled
      trial-based evidence (A and B) demonstrated considerable variability among
      individual AI practice parameters (range, 1.3%-100%). Evidence from controlled
      trials was lower in the subspecialty fields (38.3% in AI and 38.2% in
      otolaryngology) compared with the primary care fields (55.6% in pediatrics and
      86.1% in internal medicine). CONCLUSION: Considerable variability exists in the
      strength of recommendations within the AI practice parameters. The guidelines
      created by the primary care fields rest on a larger base of evidence collected
      from controlled trials. These findings likely reflect the adopted approach of
      making recommendations for less well-studied conditions and practices in AI to
      assist practitioners and patients and at the same time highlight the myriad
      opportunities for future research.

PMID- 24856886
TI  - Stress distribution and consolidation in cartilage constituents is influenced by
      cyclic loading and osteoarthritic degeneration.
AB  - The understanding of load support mechanisms in cartilage has evolved with
      computational models that better mimic the tissue ultrastructure. Fibril
      reinforced poroelastic models can reproduce cartilage behaviour in a variety of
      test conditions and can be used to model tissue anisotropy as well as assess
      stress and pressure partitioning to the tissue constituents. The goal of this
      study was to examine the stress distribution in the fibrillar and non-fibrillar
      solid phase and pressure in the fluid phase of cartilage in axisymmetric models
      of a healthy and osteoarthritic hip joint. Material properties, based on values
      from the literature, were assigned to the fibrillar and poroelastic components of
      cartilage and cancellous and subchondral compact bone regions. A cyclic load
      representing walking was applied for 25 cycles. Contact stresses in the fibrillar
      and non-fibrillar solid phase supported less than 1% of the contact force and
      increased only minimally with load cycles. Simulated proteoglycan depletion
      increased stresses in the radial and tangential collagen fibrils, whereas
      fibrillation of the tangential fibrils resulted in increased compressive stress
      in the non-fibrillar component and tensile stress in the radial fibrils. However
      neither had an effect on fluid pressure. Subchondral sclerosis was found to have
      the largest effect, resulting in increased fluid pressure, non-fibrillar
      compressive stress, tangential fibril stress and greater cartilage consolidation.
      Subchondral bone stiffening may play an important role in the degenerative
      cascade and may adversely affect tissue repair and regeneration treatments. 

PMID- 24856887
TI  - Subject-specific planning of femoroplasty: a combined evolutionary optimization
      and particle diffusion model approach.
AB  - A potential effective treatment for prevention of osteoporotic hip fractures is
      augmentation of the mechanical properties of the femur by injecting it with
      agents such as (PMMA) bone cement - femoroplasty. The operation, however, is only
      in research stage and can benefit substantially from computer planning and
      optimization. We report the results of computational planning and optimization of
      the procedure for biomechanical evaluation. An evolutionary optimization method
      was used to optimally place the cement in finite element (FE) models of seven
      osteoporotic bone specimens. The optimization, with some inter-specimen
      variations, suggested that areas close to the cortex in the superior and inferior
      of the neck and supero-lateral aspect of the greater trochanter will benefit from
      augmentation. We then used a particle-based model for bone cement diffusion
      simulation to match the optimized pattern, taking into account the limitations of
      the actual surgery, including limited volume of injection to prevent thermal
      necrosis. Simulations showed that the yield load can be significantly increased
      by more than 30%, using only 9 ml of bone cement. This increase is comparable to
      previous literature reports where gross filling of the bone was employed instead,
      using more than 40 ml of cement. These findings, along with the differences in
      the optimized plans between specimens, emphasize the need for subject-specific
      models for effective planning of femoral augmentation.

PMID- 24856888
TI  - Three-dimensional bending, torsion and axial compression of the femoropopliteal
      artery during limb flexion.
AB  - High failure rates of femoropopliteal artery reconstruction are commonly
      attributed to complex 3D arterial deformations that occur with limb movement. The
      purpose of this study was to develop a method for accurate assessment of these
      deformations. Custom-made stainless-steel markers were deployed into 5 in situ
      cadaveric femoropopliteal arteries using fluoroscopy. Thin-section CT images were
      acquired with each limb in the straight and acutely bent states. Image
      segmentation and 3D reconstruction allowed comparison of the relative locations
      of each intra-arterial marker position for determination of the artery's bending,
      torsion and axial compression. After imaging, each artery was excised for
      histological analysis using Verhoeff-Van Gieson staining. Femoropopliteal
      arteries deformed non-uniformly with highly localized deformations in the
      proximal superficial femoral artery, and between the adductor hiatus and distal
      popliteal artery. The largest bending (11+/-3-6+/-1 mm radius of curvature),
      twisting (28+/-9-77+/-27 degrees /cm) and axial compression (19+/-10-30+/-8%)
      were registered at the adductor hiatus and the below knee popliteal artery. These
      deformations were 3.7, 19 and 2.5 fold more severe than values currently reported
      in the literature. Histology demonstrated a distinct sub-adventitial layer of
      longitudinally oriented elastin fibers with intimal thickening in the segments
      with the largest deformations. This endovascular intra-arterial marker technique
      can quantify the non-uniform 3D deformations of the femoropopliteal artery during
      knee flexion without disturbing surrounding structures. We demonstrate that 3D
      arterial bending, torsion and compression in the flexed lower limb are highly
      localized and are substantially more severe than previously reported.

PMID- 24856893
TI  - Relationships between the varied ciliated respiratory epithelium abnormalities
      and severity of Mycoplasma pneumoniae pneumonia.
AB  - BACKGROUND: The pathogenesis of Mycoplasma pneumoniae infection involves
      cytoadherence of M. pneumoniae to the ciliated respiratory epithelium (CRE),
      followed by CRE injury caused by the M. pneumoniae. However, whether CRE
      abnormalities are related to the severity of M. pneumoniae pneumonia (MP) remains
      to be determined. METHODS: Thirty-eight patients with MP and 8 controls who
      underwent fiber-optic bronchoscopy with bronchial biopsy were included in this
      study. Patients with MP were divided into 2 groups: a mild disease group (12
      patients) and a severe disease group (26 patients). The clinical features,
      laboratory findings, chest radiographic findings, and CRE abnormalities were
      characterized. RESULTS: Patients with severe pneumonia had a higher epithelial
      integrity score than those with mild pneumonia (5.1 +/- 0.76 vs 3.8 +/- 0.75; p <
      0.01). Patients with severe CRE abnormalities had a longer duration of fever (p <
      0.01), higher C-reactive protein (p < 0.01), and lower proportion of blood
      lymphocytes (p < 0.05) compared to those with mild abnormalities. Patients with a
      positive bacteria culture had a higher epithelial integrity score compared to
      those with a negative culture (6.0 +/- 0.44 vs 4.8 +/- 0.71; p < 0.01).
      CONCLUSIONS: CRE abnormalities are closely related to the severity of MP. These
      findings extend our current knowledge of MP.

PMID- 24856894
TI  - Manufacturing models permitting roll out/scale out of clinically led autologous
      cell therapies: regulatory and scientific challenges for comparability.
AB  - Manufacturing of more-than-minimally manipulated autologous cell therapies
      presents a number of unique challenges driven by complex supply logistics and the
      need to scale out production to multiple manufacturing sites or near the patient
      within hospital settings. The existing regulatory structure in Europe and the
      United States imposes a requirement to establish and maintain comparability
      between sites. Under a single market authorization, this is likely to become an
      unsurmountable burden beyond two or three sites. Unless alternative manufacturing
      approaches can be found to bridge the regulatory challenge of comparability,
      realizing a sustainable and investable business model for affordable autologous
      cell therapy supply is likely to be extremely demanding. Without a proactive
      approach by the regulators to close this "translational gap," these products may
      not progress down the development pipeline, threatening patient accessibility to
      an increasing number of clinician-led autologous cellular therapies that are
      already demonstrating patient benefits. We propose three prospective
      manufacturing models for the scale out/roll out of more-than-minimally
      manipulated clinically led autologous cell therapy products and test their
      prospects for addressing the challenge of product comparability with a selected
      expert reference panel of US and UK thought leaders. This paper presents the
      perspectives and insights of the panel and identifies where operational,
      technological and scientific improvements should be prioritized. The main purpose
      of this report is to solicit feedback and seek input from key stakeholders active
      in the field of autologous cell therapy in establishing a consensus-based
      manufacturing approach that may permit the roll out of clinically led autologous
      cell therapies. 

PMID- 24856896
TI  - Upregulation of NKG2D ligands in acute lymphoblastic leukemia and non-Hodgkin
      lymphoma cells by romidepsin and enhanced in vitro and in vivo natural killer
      cell cytotoxicity.
AB  - BACKGROUND AIMS: There is a critical need to prevent and/or treat hematological
      relapse after allogeneic hematopoietic stem cell transplantation. The activating
      NKG2D receptor expressed on natural killer (NK) cells, when engaged by its
      corresponding ligands (MIC A/B), activates NK cells to become cytotoxic against
      malignant cells. METHODS: We incubated acute lymphoblastic leukemia and non
      Hodgkin lymphoma cells for 24 h with 10 ng/mL of romidepsin. Flow cytometry was
      performed to demonstrate changes in surface expression of NKG2D ligands MIC A/B.
      In vitro and in vivo cytotoxicity was measured by means of modified Europium
      assay, and non-obese diabetic/severe combined immunodeficiency mice were
      xenografted with RS 4:11 cells. RESULTS: We demonstrated an approximately 50,
      200, 1300 and 180-fold increase in the number of cells positive for the surface
      expression of MIC A/B in RS 4:11 (P < 0.001), REH (P < 0.001), Ramos (P < 0.001)
      and Jurkat cells (P < 0.001), respectively. We further demonstrated a significant
      increase in NK cell-mediated in vitro cytotoxicity against RS 4:11 (P < 0.004),
      Ramos (P < 0.05), Jurkat (P < 0.001) and REH cells (P < 0.01), respectively.
      Romidepsin-mediated NK cytotoxicity was blocked by pre-incubating NK cells with
      anti-NKG2D-Fc in RS 4:11 (P < 0.03) and Ramos cells (P < 0.01), respectively.
      Finally, non-obese diabetic/severe combined immunodeficiency mice xenografted
      with RS 4:11 cells had a significant increase in survival (P < 0.02) in mice
      treated with romidepsin and interleukin-2-activated NK cells compared with each
      of these other treatment groups. CONCLUSIONS: Romidepsin significantly enhanced
      in vitro and in vivo NK cell cytotoxicity mediated in part by increased MIC A/B
      expression on malignant cells. This translational approach of the use of
      romidepsin and interleukin-2-activated NK cells should be considered in patients
      with relapsed/refractory leukemia or lymphoma.

PMID- 24856895
TI  - Opportunities and limitations of natural killer cells as adoptive therapy for
      malignant disease.
AB  - Although natural killer (NK) cells can be readily generated for adoptive therapy
      with current techniques, their optimal application to treat malignant diseases
      requires an appreciation of the dynamic balance between signals that either
      synergize with or antagonize each other. Individuals display wide differences in
      NK function that determine their therapeutic efficacy. The ability of NK cells to
      kill target cells or produce cytokines depends on the balance between signals
      from activating and inhibitory cell-surface receptors. The selection of NK cells
      with a predominant activating profile is critical for delivering successful anti
      tumor activity. This can be achieved through selection of killer immunoglobulin
      like receptor-mismatched NK donors and by use of blocking molecules against
      inhibitory pathways. Optimum NK cytotoxicity may require licensing or priming
      with tumor cells. Recent discoveries in the molecular and cellular biology of NK
      cells inform in the design of new strategies, including adjuvant therapies, to
      maximize the cytotoxic potential of NK cells for adoptive transfer to treat human
      malignancies. 

PMID- 24856897
TI  - Except for C-C chemokine receptor 7 expression, monocyte-derived dendritic cells
      from patients with multiple sclerosis are functionally comparable to those of
      healthy controls.
AB  - BACKGROUND AIMS: Dendritic cell (DC)-based immunotherapy has shown potential to
      counteract autoimmunity in multiple sclerosis (MS). METHODS: We compared the
      phenotype and T-cell stimulatory capacity of in vitro generated monocyte-derived
      DC from MS patients with those from healthy controls. RESULTS: Except for an
      increase in the number of C-C chemokine receptor 7-expressing DC from MS
      patients, no major differences were found between groups in the expression of
      maturation-associated membrane markers or in the in vitro capacity to stimulate
      autologous T cells. CONCLUSIONS: Our observations may pave the way for the
      development of patient-tailored DC-based vaccination strategies to treat MS.

PMID- 24856898
TI  - Standardization of Good Manufacturing Practice-compliant production of bone
      marrow-derived human mesenchymal stromal cells for immunotherapeutic
      applications.
AB  - BACKGROUND AIMS: Human mesenchymal stem or stromal cells (MSCs) represent a
      potential resource not only for regenerative medicine but also for
      immunomodulatory cell therapies. The application of different MSC culture
      protocols has significantly hampered the comparability of experimental and
      clinical data from different laboratories and has posed a major obstacle for
      multicenter clinical trials. Manufacturing of cell products for clinical
      application in the European Community must be conducted in compliance with Good
      Manufacturing Practice and requires a manufacturing license. In Germany, the Paul
      Ehrlich-Institut as the Federal Authority for Vaccines and Biomedicines is
      critically involved in the approval process. METHODS: This report summarizes a
      consensus meeting between researchers, clinicians and regulatory experts on
      standard quality requirements for MSC production. RESULTS: The strategy for
      quality control testing depends on the product's cell composition, the
      manufacturing process and the indication and target patient population. Important
      quality criteria in this sense are, among others, the immunophenotype of the
      cells, composition of the culture medium and the risk for malignant
      transformation, as well as aging and the immunosuppressive potential of the
      manufactured MSCs. CONCLUSIONS: This position paper intends to provide relevant
      information to interested parties regarding these criteria to foster the
      development of scientifically valid and harmonized quality standards and to
      support approval of MSC-based investigational medicinal products.

PMID- 24856899
TI  - Subharmonic aided pressure estimation for monitoring interstitial fluid pressure
      in tumours--in vitro and in vivo proof of concept.
AB  - The feasibility of using subharmonic aided pressure estimation (SHAPE) to
      noninvasively estimate interstitial fluid pressure (IFP) was studied. In vitro,
      radiofrequency signals, from 0.2 ml/l of Definity (Lantheus Medical Imaging, N
      Billerica, MA) were acquired within a water-tank with a Sonix RP ultrasound
      scanner (Analogic Ultrasound, Richmond, BC, Canada; fT/R=6.7/3.35 MHz and
      fT/R=10/5 MHz) and the subharmonic amplitudes of the signals were compared over 0
      50 mmHg. In vivo, five swine with naturally occurring melanomas were studied.
      Subharmonic signals were acquired from tumours and surrounding tissue during
      infusion of Definity and compared to needle-based pressure measurements. Both in
      vitro and in vivo, an inverse linear relationship between hydrostatic pressure
      and subharmonic amplitude was observed with r(2)=0.63-0.95; p<0.05, maximum
      amplitude drop 11.36 dB at 10 MHz and -8 dB, and r(2) as high as 0.97; p<0.02 (10
      MHz and -4/-8 dB most promising), respectively, indicating that SHAPE may be
      useful in monitoring IFP.

PMID- 24856901
TI  - Dynamic interactions between poly(3-hexylthiophene) and single-walled carbon
      nanotubes in marginal solvent.
AB  - Interfacial interactions between conjugated polymers and carbon nanotubes are
      pivotal in determining the device performance of nanotube-based polymer
      electronic devices. Here, we report on interfacial structures and crystallization
      kinetics of poly(3-hexylthiophene) (P3HT) in the presence of single-walled carbon
      nanotubes (SWNTs) in anisole by means of transmission electron microscope (TEM)
      and ultraviolet-visible (UV-vis) absorption spectroscopy. Confined on SWNT
      surfaces, the P3HT forms nanofibril crystals perpendicular to the long axis of
      SWNTs. The equilibrium dissolution temperature of the P3HT crystals in anisole is
      determined to be 381 +/- 10 K according to the Hoffman-Weeks extrapolation
      approach. Upon cooling, the polymer solution spontaneously undergoes a time
      dependent chromism. Various kinetics factors such as crystallization temperature,
      concentration, and SWNT loading have been investigated. It is found that the
      growth rate (G) of the crystals scales with concentration (C) as G ? C(1.70+/
      0.16). The Avrami model is utilized to analyze the nucleation mechanism and the
      Avrami exponents vary between 1.0 and 1.3. The Lauritzen-Hoffman theory is
      applied to study the chain-folding process. The fold surface free energy is
      calculated to be (5.28-11.9) * 10(-2) J m(-2). It is evident that the addition of
      0.30 wt % SWNTs reduces the fold surface free energy by 55.6%. 

PMID- 24856900
TI  - miR-155 activates cytokine gene expression in Th17 cells by regulating the DNA
      binding protein Jarid2 to relieve polycomb-mediated repression.
AB  - Specification of the T helper 17 (Th17) cell lineage requires a well-defined set
      of transcription factors, but how these integrate with posttranscriptional and
      epigenetic programs to regulate gene expression is poorly understood. Here we
      found defective Th17 cell cytokine expression in miR-155-deficient CD4+ T cells
      in vitro and in vivo. Mir155 was bound by Th17 cell transcription factors and was
      highly expressed during Th17 cell differentiation. miR-155-deficient Th17 and T
      regulatory (Treg) cells expressed increased amounts of Jarid2, a DNA-binding
      protein that recruits the Polycomb Repressive Complex 2 (PRC2) to chromatin. PRC2
      binding to chromatin and H3K27 histone methylation was increased in miR-155
      deficient cells, coinciding with failure to express Il22, Il10, Il9, and Atf3.
      Defects in Th17 cell cytokine expression and Treg cell homeostasis in the absence
      of Mir155 could be partially suppressed by Jarid2 deletion. Thus, miR-155
      contributes to Th17 cell function by suppressing the inhibitory effects of
      Jarid2.

PMID- 24856902
TI  - Inteleukin-23 promotes interferon-alpha responsiveness in hepatitis C virus/HIV
      coinfected patients.
AB  - Patients coinfected with HIV and hepatitis C virus (HCV) have poor to modest
      rates of response with interferon-based therapies, which remain a backbone of the
      treatment in HIV/HCV-coinfected patients. The mechanisms responsible for poor
      responsiveness to interferon are not well described. In this study a targeted
      proteomic analysis of plasma from 42 patients infected with both HIV and HCV and
      undergoing therapy for HCV with peginterferon and ribavirin was performed. Higher
      baseline plasma levels of interleukin (IL)-23 were associated with sustained
      virologic response. Further investigation of how IL-23 facilitates interferon
      (IFN) responsiveness, as evidenced by a >2-fold increase in most interferon
      stimulated genes (ISGs), revealed that IL-23 indirectly enhances IFN signaling in
      peripheral blood mononuclear cells and HCV continuous culture system by
      preventing the down-regulation of the IFNAR2 receptor after exposure to IFN
      alpha. These findings suggest a unique role of the IL-23 pathway in enhancing
      host response to type I interferons, thereby facilitating eradication of HCV. Low
      levels of IL-23 present in plasma of nonresponders may reflect an impaired immune
      state that in the case of HIV/HCV-coinfected subjects could potentially lead to
      disruption of TH17 CD4(+) T cells. This study suggests a major role for HIV
      associated immune dysregulation present in HIV-infected subjects that
      subsequently determines the overall responsiveness to exogenous interferon-alpha
      based HCV therapy.

PMID- 24856903
TI  - Identification and bioactivity of 3-epi-xestoaminol C isolated from the New
      Zealand brown alga Xiphophora chondrophylla.
AB  - We report here the bioassay-guided isolation of a new 1-deoxysphingoid, 3-epi
      xestoaminol C (1), isolated from the New Zealand brown alga Xiphophora
      chondrophylla. This is the first report of a 1-deoxysphingoid from a brown alga.
      We describe the isolation and full structure elucidation of this compound,
      including its absolute configuration, along with its bioactivity against
      mycobacteria and mammalian cell lines and preliminary mechanism of action studies
      using yeast chemical genomics. 

PMID- 24856904
TI  - Core-shell particles: preparation, fundamentals and applications in high
      performance liquid chromatography.
AB  - The challenges in HPLC are fast and efficient separation for a wide range of
      samples. Fast separation often results in very high operating pressure, which
      places a huge burden on HPLC instrumentation. In recent years, core-shell silica
      microspheres (with a solid core and a porous shell, also known as fused-core or
      superficially porous microspheres) have been widely investigated and used for
      highly efficient and fast separation with reasonably low pressure for separation
      of small molecules, large molecules and complex samples. In this review, we
      firstly show the types of core-shell particles and how they are generally
      prepared, focusing on the methods used to produce core-shell silica particles for
      chromatographic applications. The fundamentals are discussed on why core-shell
      particles can perform better with low back pressure, in terms of van Deemter
      equation and kinetic plots. The core-shell particles are compared with totally
      porous silica particles and also monolithic columns. The use of columns packed
      with core-shell particles in different types of liquid chromatography is then
      discussed, followed by illustrating example applications of such columns for
      separation of various types of samples. The review is completed with conclusion
      and a brief perspective on future development of core-shell particles in
      chromatography. 

PMID- 24856905
TI  - An optical relay approach to very low cost hybrid polymer-complementary metal
      oxide semiconductor electrophoresis instrumentation.
AB  - Electrophoresis is an integral part of many molecular diagnostics protocols and
      an inexpensive implementation would greatly facilitate point-of-care (POC)
      applications. However, the high instrumentation cost presents a substantial
      barrier, much of it associated with fluorescence detection. The cost of such
      systems could be substantially reduced by placing the fluidic channel and
      photodiode directly above the detector in order to collect a larger portion of
      the fluorescent light. In future, this could be achieved through the integration
      and monolithic fabrication of photoresist microchannels on complementary metal
      oxide semiconductor microelectronics (CMOS). However, the development of such a
      device is expensive due to high non-recurring engineering costs. To facilitate
      that development, we present a system that utilises an optical relay to integrate
      low-cost polymeric microfluidics with a CMOS chip that provides a photodiode,
      analog-digital conversion and a standard serial communication interface. This
      system embodies an intermediate level of microelectronic integration, and
      significantly decreases development costs. With a limit of detection of 1.3+/
      0.4nM of fluorescently end-labeled deoxyribonucleic acid (DNA), it is suitable
      for diagnostic applications. 

PMID- 24856906
TI  - Fabrication and investigation of electrochromatographic columns with a simplex
      configuration.
AB  - Duplex capillary columns with a packed and an open section are widely used in
      electrochromatography (CEC). The duplex column configuration leads to non-uniform
      voltage drop, electrical field distribution and separation performance. It also
      adds to the complexity in understanding and optimizing electrochromatographic
      process. In this study, we introduced a simplex column configuration based on
      single particle fritting technology. The new column configuration has an
      essentially uniform packed bed through the entire column length, with only 1mm
      length left unpacked serving as the optical detection window. The study shows
      that a simplex column has higher separation efficiency than a duplex column,
      especially at the high voltage range, due to the consistent distribution of
      electrical field over the column length. In comparison to the duplex column, the
      simplex column presented a lower flow rate at the same applied voltage,
      suggesting that an open section may support a higher speed than a packed section.
      In practice, the long and short ends of the simplex column could be used as
      independent CEC columns respectively. This "two-in-one" bi-functional column
      configuration provided extra flexibilities in selecting and optimizing
      electrochromatographic conditions. 

PMID- 24856909
TI  - Pharmacotherapy of focal epilepsy.
AB  - INTRODUCTION: Epilepsy is the most common neurological condition worldwide with
      significant psychosocial and physical morbidity. Its management requires
      expertise and good pharmacological knowledge of the available options. AREAS
      COVERED: This review covers the management of focal epilepsy addressing the
      common questions arising through the patients' journey, including timing of
      starting initial treatment, monotherapy options, add-on treatment for refractory
      cases and withdrawal of medication during remission. EXPERT OPINION: Initiating
      anti-epileptic drug (AED) treatment requires assessment of patient preferences
      and of evidence of benefit and harm. Evidence of benefit will come primarily from
      randomised controlled trials, although in epilepsy, most trials are undertaken to
      inform regulatory decision and have important limitations for informing clinical
      decisions. Evidence about harm may come not only from randomised trials but also
      from other sources. Most patients will start treatment following a second focal
      seizure. Carbamazepine and lamotrigine are good initial monotherapy options.
      Newer AEDs have proof of efficacy as monotherapy but evidence is insufficient to
      recommend them as first-line treatments. For refractory cases, there are an
      increasing number of AEDs available, but evidence of efficacy is primarily from
      placebo-controlled trials, and there is no robust evidence to inform a choice
      among treatments.

PMID- 24856910
TI  - Outcomes after abdominal aortic aneurysm repair requiring a suprarenal cross
      clamp.
AB  - OBJECTIVE: The objective of this study was to analyze the early and late outcomes
      of patients who require a suprarenal aortic cross-clamp during elective open
      repair of an abdominal aortic aneurysm (AAA). METHODS: Patients from 1998 to 2012
      who required a suprarenal aortic cross-clamp during elective open AAA repair were
      reviewed. Data abstracted included demographics and comorbidities; preoperative,
      perioperative, and late renal function; late interventions related to AAA repair;
      and late mortality. A decrease in renal function was defined as a >30% decline in
      estimated glomerular filtration rate (eGFR) compared with the preoperative value.
      Primary outcomes included renal function, intervention-free survival, and overall
      survival. RESULTS: During the study period, 211 patients underwent open elective
      or urgent AAA repair; 69 required a suprarenal cross-clamp. The mean age was 71
      years, and 80% were men. The mean preoperative creatinine concentration was 1.2
      mg/dL, and the mean preoperative eGFR was 66 mL/min/1.73 m2. Location of the
      aortic cross-clamp was suprarenal (37), supramesenteric (21), and supraceliac
      (11). Perioperatively, 21 patients (30%) experienced a significant decrease in
      eGFR; four patients required hemodialysis. Six patients had full recovery of
      renal function by discharge. Perioperative morbidity and mortality were 35% and
      4%, respectively. At a mean follow-up of 3 years, seven patients had an eGFR
      significantly less than the preoperative value. Late interventions related to the
      AAA repair were required in eight patients. Indications included wound
      complication (3), anastomotic aneurysm (2), incisional hernia (1), anastomotic
      graft stenosis (1), and proximal aortic dilation (1). Overall 5-year intervention
      free survival was 62% and overall survival 77%. Intervention-free survival was
      enhanced by antiplatelet use (P = .04), whereas overall survival was decreased by
      chronic obstructive pulmonary disease (P = .003) and perioperative pneumonia (P =
      .001). CONCLUSIONS: More than a quarter of patients requiring a suprarenal cross
      clamp during open AAA repair experience renal dysfunction. Late graft-related
      complications are few, with preoperative and perioperative pulmonary function
      negatively affecting overall patient survival.

PMID- 24856911
TI  - Mold management of wetted carpet.
AB  - This study evaluated the growth and removal of fungi on wetted carpet using newly
      designed technologies that rely on physical principles of steam, heat, and fluid
      flow. Sixty samples of carpet were embedded with heat-treated house dust,
      followed by embedding, wearing with a hexapod, and wetting. Samples were
      inoculated using a liquid suspension of Cladosporium sphaerospermum prior to
      placement over a water-saturated foam pad. Incubation times were 24 hr, 7 days,
      and 30 days. Cleaning was performed using three methods; high-flow hot water
      extraction, hot water and detergent, and steam. Fungal loading increased from
      approximately 1500 colony forming units per area (CFU/cm(2)) in 24 hr to a
      maximum of approximately 10,200 CFU/cm(2) after 7 days with a slight decline to
      9700 CFU/cm(2) after 30 days incubation. Statistically significant differences
      were found among all three methods for removal of fungi for all three time
      periods (p < 0.05). Steam-vapor was significantly better than the alternative
      methods (p <0.001) with over 99% efficiency in mold spore decline from wetted
      carpet after 24 hr and 30 days, and over 92% efficiency after 7 days. The
      alternative methods exhibited lower efficiencies with a decline over time, from a
      maximum of 82% and 81% at 24 hr down to 60% and 43% at 30 days for detergent-hot
      water and high-flow, hot water extraction, respectively. The net effect of the
      mold management study demonstrates that while steam has a consistent fungal
      removal rate, the detergent and high-flow, hot water methods decline in
      efficiency with increasing incubation time.

PMID- 24856912
TI  - Variability of in vivo reference point indentation in skeletally mature inbred
      rats.
AB  - Reference point indentation (RPI) has emerged as a novel tool to measure material
      level biomechanical properties in vivo. Human studies have been able to
      differentiate fracture versus non-fracture patients while a dog study has shown
      the technique can differentiate drug treatment effects. The goal of this study
      was to extend this technology to the in vivo measurement of rats, one of the most
      common animal models used to study bone, with assessment of intra- and inter
      animal variability. Seventy-two skeletally mature male Sprague-Dawley rats were
      subjected to in vivo RPI on the region between the tibial diaphysis and proximal
      metaphysis. RPI data were assessed using a custom MATLAB program to determine
      several outcome parameters, including first cycle indentation distance (ID-1st),
      indentation distance increase (IDI), total indentation distance (TID), first
      cycle unloading slope (US-1st), and first cycle energy dissipation (ED-1st).
      Intra-animal variability ranged from 13% to 21% with US-1st and Tot Ed 1st-L
      being the least variable properties and IDI the most highly variable. Inter
      animal variability ranged from 16% (US-1st) to 25% (ED-1st and IDI). Based on
      these data, group size estimates would need to range from 9 to 18/group to
      achieve sufficient power for detecting a 25% difference in a two-group
      experiment. Repeat tests on the contralateral limb of a small cohort of animals
      (n=17) showed non-significant differences over 28 days ranging from -6% to -18%.
      These results provide important data on RPI variability (intra- and inter-animal)
      in rats that can be used to properly power future experiments using this
      technique. 

PMID- 24856913
TI  - Validity and reliability of 3D marker based scapular motion analysis: a
      systematic review.
AB  - Methods based on cutaneous markers are the most popular for the recording of
      three dimensional scapular motion analysis. Numerous methods have been evaluated,
      each showing different levels of accuracy and reliability. The aim of this review
      was to report the metrological properties of 3D scapular kinematic measurements
      using cutaneous markers and to make recommendations based on metrological
      evidence. A database search was conducted using relevant keywords and
      inclusion/exclusion criteria in 5 databases. 19 articles were included and
      assessed using a quality score. Concurrent validity and reliability were analyzed
      for each method. Six different methods are reported in the literature, each based
      on different marker locations and post collection computations. The acromion
      marker cluster (AMC) method coupled with a calibration of the scapula with the
      arm at rest is the most studied method. Below 90-100 degrees  of humeral
      elevation, this method is accurate to about 5 degrees  during arm flexion and 7
      degrees  during arm abduction compared to palpation (average of the 3 scapular
      rotation errors). Good to excellent within-session reliability and moderate to
      excellent between-session reliability have been reported. The AMC method can be
      improved using different or multiple calibrations. Other methods using different
      marker locations or more markers on the scapula blade have been described but are
      less accurate than AMC methods. Based on current metrological evidence we would
      recommend (1) the use of an AMC located at the junction of the scapular spine and
      the acromion, (2) the use of a single calibration at rest if the task does not
      reach 90 degrees  of humeral elevation, (3) the use of a second calibration (at
      90 degrees  or 120 degrees  of humeral elevation), or multiple calibrations above
      90 degrees  of humeral elevation. 

PMID- 24856914
TI  - Cranial anatomy of the Duchesnean primate Rooneyia viejaensis: new insights from
      high resolution computed tomography.
AB  - Rooneyia viejaensis is a North American Eocene primate of uncertain phylogenetic
      affinities. Although the external cranial anatomy of Rooneyia is well studied,
      various authors have suggested that Rooneyia is a stem haplorhine, stem
      strepsirrhine, stem tarsiiform, or stem anthropoid. Here we describe the internal
      cranial anatomy of the Rooneyia holotype based on micro-computed tomography and
      discuss the phylogenetic implications of this anatomy. Precise measurements of
      the natural endocast filling the braincase of the Rooneyia holotype reveal that
      the genus had a relative brain size comparable to some living callitrichines and
      strepsirrhines. Rooneyia was thus probably more encephalized than any other known
      omomyiform, adapiform, or plesiadapiform. Relative olfactory bulb size in
      Rooneyia was most comparable to some living strepsirrhines and the stem
      anthropoid Parapithecus. The nasal fossa of Rooneyia resembled that of living
      strepsirrhines in retaining an obliquely oriented nasolacrimal canal, four
      ethmoturbinals, and an olfactory recess separated from the nasopharyngeal meatus
      by a transverse lamina. The ear region of Rooneyia is characterized by large and
      complete canals for both the stapedial and promontory branches of the internal
      carotid artery. Rooneyia also retains a patent parotic fissure and thus had an
      extrabullar origin of the stapedius muscle. In most of these respects, Rooneyia
      exhibits the condition that is presumed to be primitive for crown primates and
      lacks a number of key crown haplorhine synapomorphies (e.g., a dorso-ventrally
      oriented nasolacrimal canal, loss of the olfactory recess, loss of ethmoturbinals
      3-4, loss or extreme reduction of the stapedial canal due to involution of the
      stapedial artery). These data are consistent with the hypothesis that Rooneyia is
      an advanced stem primate or a basal crown primate but are inconsistent with prior
      suggestions that Rooneyia is a crown haplorhine. 

PMID- 24856919
TI  - Analytical assessment about the simultaneous quantification of releasable
      pharmaceutical relevant inorganic nanoparticles in tap water and domestic waste
      water.
AB  - For pharmaceutical applications, the use of inorganic engineered nanoparticles is
      of growing interest while silver (Ag) and gold (Au) are the most relevant
      elements. A few methods were developed recently but the validation and the
      application testing were quite limited. Therefore, a routinely suitable multi
      element method for the identification of nanoparticles of different sizes below
      100 nm and elemental composition by applying asymmetric flow field flow fraction
      (AF4) - inductively coupled plasma mass spectrometry (ICPMS) is developed. A
      complete validation model of the quantification of releasable pharmaceutical
      relevant inorganic nanoparticles based on Ag and Au is presented for the most
      relevant aqueous matrices of tap water and domestic waste water. The samples are
      originated from locations in the Netherlands and it is of great interest to study
      the unwanted presence of Ag and Au as nanoparticle residues due to possible
      health and environmental risks. During method development, instability effects
      are observed for 60 nm and 70 nm Ag ENPs with different capping agents. These
      effects are studied more closely in relation to matrix effects. Besides the
      methodological aspects, the obtained analytical results and relevant performance
      characteristics (e.g. measuring range, limit of detection, repeatability,
      reproducibility, trueness, and expanded uncertainty of measurement) are
      determined and discussed. For the chosen aqueous matrices, the results of the
      performance characteristics are significantly better for Au ENPs in comparison to
      Ag ENPs; e.g. repeatability and reproducibility are below 10% for all Au ENPs
      respectively maximal 27% repeatability for larger Ag ENPs. The method is a
      promising tool for the simultaneous determination of releasable pharmaceutical
      relevant inorganic nanoparticles.

PMID- 24856921
TI  - Decoupling mechanisms of platinum deposition on colloidal gold nanoparticle
      substrates.
AB  - Nanoscale platinum materials are essential components in many technologies,
      including catalytic converters and fuel cells. Combining Pt with other metals can
      enhance its performance and/or decrease the cost of the technology, and a wide
      range of strategies have been developed to capitalize on these advantages.
      However, wet chemical synthesis of Pt-containing nanoparticles (NPs) is
      challenging due to the diverse metal segregation and metal-metal redox processes
      possible under closely related experimental conditions. Here, we elucidate the
      relationship between Pt(IV) speciation and the formation of well-known NP motifs,
      including frame-like and core-shell morphologies, in Au-Pt systems. We leverage
      insights gained from these studies to induce a controlled transition from redox-
      to surface chemistry-mediated growth pathways, resulting in the formation of Pt
      NPs in epitaxial contact and linear alignment along a gold nanoprism substrate.
      Mechanistic investigations using a combination of electron microscopy and (195)Pt
      NMR spectroscopy identify Pt(IV) speciation as a crucial parameter for
      understanding and controlling the formation of Pt-containing NPs. Combined, these
      findings point toward fully bottom-up methods for deposition and organization of
      NPs on colloidal plasmonic substrates. 

PMID- 24856920
TI  - Changes in forced expiratory volume in 1 second over time in patients with
      controlled asthma at baseline.
AB  - BACKGROUND: A predominant feature of asthma is an accelerated rate of decline in
      forced expiratory volume in 1 s (FEV1), but data on the variability and factors
      associated with this change in patients with controlled asthma are largely
      unknown. METHODS: 140 patients with controlled asthma were enrolled based on the
      Global Initiative for Asthma guidelines. We examined the data of a prospective
      analysis of the association between asthma control and change in FEV1 over time.
      RESULTS: A 3-year follow-up assessment was completed in 128 patients. The mean
      rate of change in FEV1 was a decline of 22.2 mL yr(-1), with significant
      variation in the levels of change. The between patient standard deviation for the
      rate of decline was 34.1 mL yr(-1). We next classified the subjects of less than
      the 25th percentile as rapid decliners, and greater than the 25th percentile as
      non-rapid decliners. The decrease in the Asthma Control Test score over a 3-year
      period was higher for rapid decliners than that for non-rapid decliners (p <
      0.001). The rapid decliner was more likely to be older, to have higher levels of
      FeNO, and to have had severe exacerbations during the study. Patients with severe
      exacerbations had a greater annual decline in FEV1 compared to patients with no
      exacerbations (-13.6 vs. -53.2 mL yr(-1), p < 0.0001). CONCLUSIONS: Among
      patients with controlled asthma at baseline, the rate of change in FEV1 is highly
      variable. Severe exacerbations are strongly associated with a rapid loss of lung
      function.

PMID- 24856922
TI  - Analytical applications of microbial fuel cells. Part I: Biochemical oxygen
      demand.
AB  - Microbial fuel cells (MFCs) are bio-electrochemical devices, where usually the
      anode (but sometimes the cathode, or both) contains microorganisms able to
      generate and sustain an electrochemical gradient which is used typically to
      generate electrical power. In the more studied set-up, the anode contains
      heterotrophic bacteria in anaerobic conditions, capable to oxidize organic
      molecules releasing protons and electrons, as well as other by-products. Released
      protons could reach the cathode (through a membrane or not) whereas electrons
      travel across an external circuit originating an easily measurable direct current
      flow. MFCs have been proposed fundamentally as electric power producing devices
      or more recently as hydrogen producing devices. Here we will review the still
      incipient development of analytical uses of MFCs or related devices or set-ups,
      in the light of a non-restrictive MFC definition, as promising tools to asset
      water quality or other measurable parameters. An introduction to biological based
      analytical methods, including bioassays and biosensors, as well as MFCs design
      and operating principles, will also be included. Besides, the use of MFCs as
      biochemical oxygen demand sensors (perhaps the main analytical application of
      MFCs) is discussed. In a companion review (Part 2), other new analytical
      applications are reviewed used for toxicity sensors, metabolic sensors, life
      detectors, and other proposed applications. 

PMID- 24856923
TI  - Protein matrix involved in the lipid retention of foie gras during cooking: a
      multimodal hyperspectral imaging study.
AB  - Denaturation of the protein matrix during heat treatment of duck foie gras was
      studied in relationship to the amount of fat loss during cooking. A low fat loss
      group was compared with a high fat loss group by histochemistry, FT-IR, and
      synchrotron UV microspectroscopy combination to characterize their protein matrix
      at different scales. After cooking, the high fat loss group showed higher
      densification of its matrix, higher ultraviolet tyrosine autofluorescence, and an
      infrared shift of the amide I band. These results revealed a higher level of
      protein denaturation and aggregation during cooking in high fat loss than in low
      fat loss foie gras. In addition, the fluorescence and infrared responses of the
      raw tissue revealed differences according to the level of fat losses after
      cooking. These findings highlight the importance of the supramolecular state of
      the protein matrix in determining the fat loss of foie gras. 

PMID- 24856924
TI  - Studying the antibody repertoire after vaccination: practical applications.
AB  - Nearly all licensed vaccines have been developed to confer protection against
      infectious diseases by stimulating the production of antibodies by B cells, but
      the nature of a successful antibody response has been difficult to capture.
      Recent advances in next-generation sequencing (NGS) technology have allowed high
      resolution characterization of the antibody repertoire, and of the changes that
      occur following vaccination. These approaches have yielded important insights
      into the B cell response, and have raised the possibility of using specific
      antibody sequences as measures of vaccine immunogenicity. Here, we review recent
      findings based on antibody repertoire sequencing, and discuss potential
      applications of these new technologies and of the analyses of the increasing
      volume of antibody sequence data in the context of vaccine development. 

PMID- 24856925
TI  - Use of double skin paddle for pharyngoesophageal reconstruction using tubed
      radial forearm free flap.

PMID- 24856926
TI  - Piezoelectric osteoarthrectomy for management of ankylosis of the
      temporomandibular joint.
AB  - We describe the use of a piezoelectric osteotome for removal of bone in patients
      with ankylosis of the temporomandibular joint (TMJ) and its advantages over
      conventional techniques. We studied 35 patients with ankylosis of 62 TMJ (27
      bilateral and 8 unilateral, 2 recurrent) who were treated by gap arthroplasty
      between 1 January 2011 and 31 December 2012. We used a preauricular, with
      extended temporal, incision in all cases. The ankylosis was released with a
      piezoelectric scalpel. There were 23 men and 12 women, mean (SD) age 16 (9)
      years. We noticed a substantial reduction in bleeding with the piezoelectric bone
      cutter compared with the dental drill, though the operating time was longer. We
      noticed no bleeding from the maxillary artery or pterygoid plexus. Mean (SD)
      bleeding/side was 43 (5) ml, and mean (SD) operating time was 77 (8) minutes for
      a single joint. At 6 months' follow-up mean (SD) passive mouth opening was 35 (3)
      mm. Piezoelectric bone removal for the release of ankylosis of the TMJ is
      associated with minimal bleeding, few postoperative complications, and
      satisfactory mouth opening at 6 months' follow up.

PMID- 24856927
TI  - Staging of osteonecrosis of the jaw requires computed tomography for accurate
      definition of the extent of bony disease.
AB  - Management of osteonecrosis of the jaw associated with antiresorptive agents is
      challenging, and outcomes are unpredictable. The severity of disease is the main
      guide to management, and can help to predict prognosis. Most available staging
      systems for osteonecrosis, including the widely-used American Association of Oral
      and Maxillofacial Surgeons (AAOMS) system, classify severity on the basis of
      clinical and radiographic findings. However, clinical inspection and radiography
      are limited in their ability to identify the extent of necrotic bone disease
      compared with computed tomography (CT). We have organised a large multicentre
      retrospective study (known as MISSION) to investigate the agreement between the
      AAOMS staging system and the extent of osteonecrosis of the jaw (focal compared
      with diffuse involvement of bone) as detected on CT. We studied 799 patients with
      detailed clinical phenotyping who had CT images taken. Features of diffuse bone
      disease were identified on CT within all AAOMS stages (20%, 8%, 48%, and 24% of
      patients in stages 0, 1, 2, and 3, respectively). Of the patients classified as
      stage 0, 110/192 (57%) had diffuse disease on CT, and about 1 in 3 with CT
      evidence of diffuse bone disease was misclassified by the AAOMS system as having
      stages 0 and 1 osteonecrosis. In addition, more than a third of patients with
      AAOMS stage 2 (142/405, 35%) had focal bone disease on CT. We conclude that the
      AAOMS staging system does not correctly identify the extent of bony disease in
      patients with osteonecrosis of the jaw.

PMID- 24856928
TI  - In vivo imaging of GLP-1R with a targeted bimodal PET/fluorescence imaging agent.
AB  - Accurate visualization and quantification of beta-cell mass is critical for the
      improved understanding, diagnosis, and treatment of both type 1 diabetes (T1D)
      and insulinoma. Here, we describe the synthesis of a bimodal imaging probe
      (PET/fluorescence) for imaging GLP-1R expression in the pancreas and in
      pancreatic islet cell tumors. The conjugation of a bimodal imaging tag containing
      a near-infrared fluorescent dye, and the copper chelator sarcophagine to the GLP
      1R targeting peptide exendin-4 provided the basis for the bimodal imaging probe.
      Conjugation was performed via a novel sequential one-pot synthetic procedure
      including (64)Cu radiolabeling and copper-catalyzed click-conjugation. The
      bimodal imaging agent (64)Cu-E4-Fl was synthesized in good radiochemical yield
      and specific activity (RCY = 36%, specific activity: 141 MUCi/MUg, >98%
      radiochemical purity). The agent showed good performance in vivo and ex vivo,
      visualizing small xenografts (<2 mm) with PET and pancreatic beta-cell mass by
      phosphor autoradiography. Using the fluorescent properties of the probe, we were
      able to detect individual pancreatic islets, confirming specific binding to GLP
      1R and surpassing the sensitivity of the radioactive label. The use of bimodal
      PET/fluorescent imaging probes is promising for preoperative imaging and
      fluorescence-assisted analysis of patient tissues. We believe that our procedure
      could become relevant as a protocol for the development of bimodal imaging
      agents. 

PMID- 24856930
TI  - DNAJC19, a mitochondrial cochaperone associated with cardiomyopathy, forms a
      complex with prohibitins to regulate cardiolipin remodeling.
AB  - Prohibitins form large protein and lipid scaffolds in the inner membrane of
      mitochondria that are required for mitochondrial morphogenesis, neuronal
      survival, and normal lifespan. Here, we have defined the interactome of PHB2 in
      mitochondria and identified DNAJC19, mutated in dilated cardiomyopathy with
      ataxia, as binding partner of PHB complexes. We observed impaired cell growth,
      defective cristae morphogenesis, and similar transcriptional responses in the
      absence of either DNAJC19 or PHB2. The loss of PHB/DNAJC19 complexes affects
      cardiolipin acylation and leads to the accumulation of cardiolipin species with
      altered acyl chains. Similar defects occur in cells lacking the transacylase
      tafazzin, which is mutated in Barth syndrome. Our experiments suggest that
      PHB/DNAJC19 membrane domains regulate cardiolipin remodeling by tafazzin and
      explain similar clinical symptoms in two inherited cardiomyopathies by an
      impaired cardiolipin metabolism in mitochondrial membranes.

PMID- 24856929
TI  - Early B cell factor 1 regulates adipocyte morphology and lipolysis in white
      adipose tissue.
AB  - White adipose tissue (WAT) morphology characterized by hypertrophy (i.e., fewer
      but larger adipocytes) associates with increased adipose inflammation, lipolysis,
      insulin resistance, and risk of diabetes. However, the causal relationships and
      the mechanisms controlling WAT morphology are unclear. Herein, we identified EBF1
      as an adipocyte-expressed transcription factor with decreased expression/activity
      in WAT hypertrophy. In human adipocytes, the regulatory targets of EBF1 were
      enriched for genes controlling lipolysis and adipocyte
      morphology/differentiation, and in both humans and murine models, reduced EBF1
      levels associated with increased lipolysis and adipose hypertrophy. Although EBF1
      did not affect adipose inflammation, TNFalpha reduced EBF1 gene expression. High
      fat diet intervention in Ebf1(+/-) mice resulted in more pronounced WAT
      hypertrophy and attenuated insulin sensitivity compared with wild-type littermate
      controls. We conclude that EBF1 is an important regulator of adipose morphology
      and fat cell lipolysis and may constitute a link between WAT inflammation,
      altered lipid metabolism, adipose hypertrophy, and insulin resistance. 

PMID- 24856931
TI  - ROS-triggered phosphorylation of complex II by Fgr kinase regulates cellular
      adaptation to fuel use.
AB  - Electron flux in the mitochondrial electron transport chain is determined by the
      superassembly of mitochondrial respiratory complexes. Different superassemblies
      are dedicated to receive electrons derived from NADH or FADH2, allowing cells to
      adapt to the particular NADH/FADH2 ratio generated from available fuel sources.
      When several fuels are available, cells adapt to the fuel best suited to their
      type or functional status (e.g., quiescent versus proliferative). We show that an
      appropriate proportion of superassemblies can be achieved by increasing CII
      activity through phosphorylation of the complex II catalytic subunit FpSDH. This
      phosphorylation is mediated by the tyrosine-kinase Fgr, which is activated by
      hydrogen peroxide. Ablation of Fgr or mutation of the FpSDH target tyrosine
      abolishes the capacity of mitochondria to adjust metabolism upon nutrient
      restriction, hypoxia/reoxygenation, and T cell activation, demonstrating the
      physiological relevance of this adaptive response.

PMID- 24856933
TI  - Obinutuzumab for B-cell malignancies.
AB  - INTRODUCTION: We analyse data for the use of obinutuzumab in the treatment of
      CD20(+) lymphoproliferative disorders with a focus on chronic lymphocytic
      leukaemia (CLL). Targeted therapy against CD20 with the mAb rituximab led to
      significant improvements in survival for patients with B-cell non-Hodgkin
      lymphoma (NHL) and is the current mainstay of treatment for CD20(+) malignancies.
      Despite this, many patients relapse or become refractory after rituximab
      containing therapies, so efforts have been made to develop better anti-CD20 mAbs.
      Obinutuzumab recently demonstrated superiority over rituximab in the only
      published Phase III study comparing the two antibodies. AREAS COVERED:
      Obinutuzumab is a humanised, anti-CD20 mAb being compared to rituximab in several
      Phase III studies. An overview of obinutuzumab, its mechanisms of action and
      results of Phase I-III studies are presented. EXPERT OPINION: The demonstration
      of superiority of obinutuzumab over rituximab in the CLL11 Phase III study is
      potentially practice-changing. Obinutuzumab has also proven safe and efficacious
      in CD20(+) NHL in Phase I/II studies and results of Phase III studies in NHL are
      eagerly awaited. The potential implications of improved outcomes for CLL and NHL
      with the introduction of this more potent anti-CD20 antibody are tremendous given
      the impressive results obtained after the introduction of rituximab over a decade
      ago.

PMID- 24856932
TI  - Estradiol regulates brown adipose tissue thermogenesis via hypothalamic AMPK.
AB  - Estrogens play a major role in the modulation of energy balance through central
      and peripheral actions. Here, we demonstrate that central action of estradiol
      (E2) inhibits AMP-activated protein kinase (AMPK) through estrogen receptor alpha
      (ERalpha) selectively in the ventromedial nucleus of the hypothalamus (VMH),
      leading to activation of thermogenesis in brown adipose tissue (BAT) through the
      sympathetic nervous system (SNS) in a feeding-independent manner. Genetic
      activation of AMPK in the VMH prevented E2-induced increase in BAT-mediated
      thermogenesis and weight loss. Notably, fluctuations in E2 levels during estrous
      cycle also modulate this integrated physiological network. Together, these
      findings demonstrate that E2 regulation of the VMH AMPK-SNS-BAT axis is an
      important determinant of energy balance and suggest that dysregulation in this
      axis may account for the common changes in energy homeostasis and obesity linked
      to dysfunction of the female gonadal axis. 

PMID- 24856934
TI  - Informing physiotherapy decisions with reliable evidence: how physiotherapists
      have contributed to Cochrane and how Cochrane has informed evidence-based
      physiotherapy.

PMID- 24856935
TI  - Physiotherapy management of whiplash-associated disorders (WAD).

PMID- 24856936
TI  - Some physiotherapy treatments may relieve menstrual pain in women with primary
      dysmenorrhea: a systematic review.
AB  - QUESTION: In women with primary dysmenorrhoea, what is the effect of
      physiotherapeutic interventions compared to control (either no treatment or
      placebo/sham) on pain and quality of life? DESIGN: Systematic review of
      randomised trials with meta-analysis. PARTICIPANTS: Women with primary
      dysmenorrhea. INTERVENTION: Any form of physiotherapy treatment. OUTCOME
      MEASURES: The primary outcome was menstrual pain intensity and the secondary
      outcome was quality of life. RESULTS: The search yielded 222 citations. Of these,
      11 were eligible randomised trials and were included in the review. Meta-analysis
      revealed statistically significant reductions in pain severity on a 0-10 scale
      from acupuncture (weighted mean difference 2.3, 95% CI 1.6 to 2.9) and
      acupressure (weighted mean difference 1.4, 95% CI 0.8 to 1.9), when compared to a
      control group receiving no treatment. However, these are likely to be placebo
      effects because when the control groups in acupuncture/acupressure trials
      received a sham instead of no treatment, pain severity did not significantly
      differ between the groups. Significant reductions in pain intensity on a 0-10
      scale were noted in individual trials of heat (by 1.8, 95% CI 0.9 to 2.7),
      transcutaneous electrical nerve stimulation (2.3, 95% CI 0.03 to 4.2), and yoga
      (3.2, 95% CI 2.2 to 4.2). Meta-analysis of two trials of spinal manipulation
      showed no significant reduction in pain. None of the included studies measured
      quality of life. CONCLUSION: Physiotherapists could consider using heat,
      transcutaneous electrical nerve stimulation, and yoga in the management of
      primary dysmenorrhea. While benefits were also identified for acupuncture and
      acupressure in no-treatment controlled trials, the absence of significant effects
      in sham-controlled trials suggests these effects are mainly attributable to
      placebo effects.

PMID- 24856937
TI  - Cyclical electrical stimulation increases strength and improves activity after
      stroke: a systematic review.
AB  - QUESTION: Does electrical stimulation increase strength after stroke and are any
      benefits maintained beyond the intervention period or carried over to activity?
      DESIGN: Systematic review with meta-analysis of randomised or controlled trials.
      PARTICIPANTS: Adults who have had a stroke. INTERVENTION: Cyclical electrical
      stimulation applied in order to increase muscle strength. OUTCOME MEASURES:
      Strength measures had to be representative of maximum voluntary contraction and
      were obtained as continuous measures of force or torque, or ordinal measures such
      as manual muscle tests. Activity was measured using direct measures of
      performance that produced continuous or ordinal data, or with scales that
      produced ordinal data. RESULTS: Sixteen trials representing 17 relevant
      comparisons were included in this systematic review. Effect sizes were calculated
      as standardised mean differences because various muscles were studied and
      different outcome measures were used. Overall, electrical stimulation increased
      strength by a standardised mean difference (SMD) of 0.47 (95% CI 0.26 to 0.68)
      and this effect was maintained beyond the intervention period (SMD 0.33, 95% CI
      0.07 to 0.60). Electrical stimulation also improved activity (SMD 0.30, 95% CI
      0.05 to 0.56) and this effect was also maintained beyond the intervention period
      (SMD 0.38, 95% CI 0.09 to 0.66). CONCLUSION: Cyclical electrical stimulation
      increases strength and improves activity after stroke. These benefits were
      maintained beyond the intervention period with a small-to-moderate effect size.
      The sustained effect on activity suggests that the benefits were incorporated
      into daily life. Review registration: PROSPERO (CRD42013003895).

PMID- 24856938
TI  - Current evidence does not support the use of Kinesio Taping in clinical practice:
      a systematic review.
AB  - QUESTIONS: Is Kinesio Taping more effective than a sham taping/placebo, no
      treatment or other interventions in people with musculoskeletal conditions? Is
      the addition of Kinesio Taping to other interventions more effective than other
      interventions alone in people with musculoskeletal conditions? DESIGN: Systematic
      review of randomised trials. PARTICIPANTS: People with musculoskeletal
      conditions. INTERVENTION: Kinesio Taping was compared with sham taping/placebo,
      no treatment, exercises, manual therapy and conventional physiotherapy. OUTCOME
      MEASURES: Pain intensity, disability, quality of life, return to work, and global
      impression of recovery. RESULTS: Twelve randomised trials involving 495
      participants were included in the review. The effectiveness of the Kinesio Taping
      was tested in participants with: shoulder pain in two trials; knee pain in three
      trials; chronic low back pain in two trials; neck pain in three trials; plantar
      fasciitis in one trial; and multiple musculoskeletal conditions in one trial. The
      methodological quality of eligible trials was moderate, with a mean of 6.1 points
      on the 10-point PEDro Scale score. Overall, Kinesio Taping was no better than
      sham taping/placebo and active comparison groups. In all comparisons where
      Kinesio Taping was better than an active or a sham control group, the effect
      sizes were small and probably not clinically significant or the trials were of
      low quality. CONCLUSION: This review provides the most updated evidence on the
      effectiveness of the Kinesio Taping for musculoskeletal conditions. The current
      evidence does not support the use of this intervention in these clinical
      populations. PROSPERO registration: CRD42012003436.

PMID- 24856939
TI  - Physical activity stimulation program for children with cerebral palsy did not
      improve physical activity: a randomised trial.
AB  - QUESTION: In children with cerebral palsy, does a 6-month physical activity
      stimulation program improve physical activity, mobility capacity, fitness,
      fatigue and attitude towards sports more than usual paediatric physiotherapy?
      DESIGN: Multicentre randomised controlled trial with concealed allocation,
      blinded assessments and intention-to-treat analysis. PARTICIPANTS: Forty-nine
      walking children (28 males) aged 7-13 years with spastic cerebral palsy and
      severity of the disability classified as Gross Motor Function Classification
      System level I-III. INTERVENTION: The intervention group followed a 6-month
      physical activity stimulation program involving counselling through motivational
      interviewing, home-based physiotherapy, and 4 months of fitness training. The
      control group continued their usual paediatric physiotherapy. OUTCOME MEASURES:
      Primary outcomes were walking activity (assessed objectively with an activity
      monitor) and parent-reported physical activity (Activity QUESTIONnaire for Adults
      and Adolescents). Secondary outcomes were: mobility capacity, consisting of Gross
      Motor Function Measure-66 (GMFM-66), walking capacity and functional strength,
      fitness (aerobic and anaerobic capacity, muscle strength), self-reported fatigue,
      and attitude towards sport (child and parent). Assessments were performed at
      baseline, 4 months, 6 months and 12 months. RESULTS: There were no significant
      intervention effects for physical activity or secondary outcomes at any
      assessment time. Positive trends were found for parent-reported time at moderate
      to-vigorous intensity (between-group change ratio=2.2, 95% CI 1.1 to 4.4) and
      GMFM-66 (mean between-group difference=2.8 points, 95% CI 0.2 to 5.4) at 6
      months, but not at 12 months. There was a trend for a small, but clinically
      irrelevant, improvement in the children's attitudes towards the disadvantages of
      sports at 6 months, and towards the advantages of sports at 12 months.
      CONCLUSIONS: This physical activity stimulation program, that combined fitness
      training, counselling and home-based therapy, was not effective in children with
      cerebral palsy. Further research should examine the potential of each component
      of the intervention for improving physical activity in this population. TRIAL
      REGISTRATION: NTR2099.

PMID- 24856940
TI  - People with stroke spend more time in active task practice, but similar time in
      walking practice, when physiotherapy rehabilitation is provided in circuit
      classes compared to individual therapy sessions: an observational study.
AB  - QUESTION: Do people with stroke spend more time in active task practice during
      circuit class therapy sessions versus individual physiotherapy sessions? Do
      people with stroke practise different tasks during circuit class therapy sessions
      versus individual physiotherapy sessions? DESIGN: Prospective, observational
      study. PARTICIPANTS: Twenty-nine people with stroke in inpatient rehabilitation
      settings. INTERVENTIONS: Individual therapy sessions and circuit class therapy
      sessions provided within a larger randomised controlled trial. OUTCOME MEASURES:
      Seventy-nine therapy sessions were video-recorded and the footage was analysed
      for time spent engaged in various categories of activity. In a subsample of 28
      videos, the number of steps taken by people with stroke per therapy session was
      counted. RESULTS: Circuit class therapy sessions were of a longer duration (mean
      difference 38.0minutes, 95% CI 29.9 to 46.1), and participants spent more time
      engaged in active task practice (mean difference 23.8minutes, 95% CI 16.1 to
      31.4) compared with individual sessions. A greater percentage of time in circuit
      class therapy sessions was spent practising tasks in sitting (mean difference
      5.3%, 95% CI 2.4 to 8.2) and in sit-to-stand practice (mean difference 2.7%, 95%
      CI 1.4 to 4.1), and a lower percentage of time in walking practice (mean
      difference 19.1%, 95% CI 10.0 to 28.1) compared with individual sessions.
      PARTICIPANTS took an average of 371 steps (SD 418) during therapy sessions and
      this did not differ significantly between group and individual sessions.
      CONCLUSION: People with stroke spent more time in active task practice, but a
      similar amount of time in walking practice when physiotherapy was offered in
      circuit class therapy sessions versus individual therapy sessions. There is a
      need for effective strategies to increase the amount of walking practice during
      physiotherapy sessions for people after stroke.

PMID- 24856942
TI  - Randomised controlled trial protocol of foot and ankle exercise for children with
      Charcot-Marie-Tooth disease.
AB  - INTRODUCTION: Charcot-Marie-Tooth disease (CMT) is one of the most commonly
      inherited neuromuscular diseases--there is no effective treatment. Foot and ankle
      weakness is a major problem for children with CMT, thus interventions that focus
      on maintaining and increasing strength may provide a solution. RESEARCH QUESTION:
      Is progressive resistance strength training an effective and safe intervention to
      improve strength, disability, gait and quality of life of children with CMT?
      PARTICIPANTS AND SETTING: Sixty children (6 to 17 years) with confirmed CMT who
      reside in Sydney, Australia will be recruited via referral from a paediatric
      neurologist, advertisements or the Australasian Paediatric CMT Registry.
      INTERVENTION: Participants will be randomised to undergo a 24-week, thrice
      weekly, high-intensity progressive resistance foot and ankle exercise programme
      (HIGH) or low-intensity foot and ankle exercise control programme (LOW).
      MEASUREMENTS: Out-come measures will be conducted at baseline, 6, 12 and 24
      months.The primary outcome is isometric dorsiflexion strength measured by hand
      held dynamometry. Secondary outcomes include disability, gait, quality of life,
      functional ankle instability and muscle volume and fatty infiltration of the
      anterior compartment of the lower leg (determined by MRI). PROCEDURE:
      Randomisation and allocation will be by a computer-generated algorithm,
      maintained and assigned by an external phone-based system, concealed to the
      investigators. Participants, parents and the outcome assessors will be blinded to
      group assignment. ANALYSIS: Treatment effect between groups is by intention-to
      treat with a linear regression approach to analysis of covariance using 95% CI
      and p < 0.05. DISCUSSION: This study is the first randomised controlled trial to
      evaluate the risks and benefits of strengthening the affected muscles in children
      with CMT. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry.
      REGISTRATION NUMBER: ACTRN12613000552785.

PMID- 24856943
TI  - Manual physiotherapy or exercise leads to sustained reductions in pain and
      physical disability in people with hip and knee osteoarthritis.

PMID- 24856944
TI  - Water-based exercise is more effective than land-based exercise for people with
      COPD and physical comorbidities.

PMID- 24856945
TI  - Progressive resistance exercise increases strength but does not improve objective
      measures of mobility in young people with cerebral palsy.

PMID- 24856946
TI  - A neuromuscular exercise program prior to hip or knee arthroplasty does not
      improve recovery of function three months after surgery.

PMID- 24856947
TI  - Fall Efficacy Scale-International (FES-I).

PMID- 24856948
TI  - National Institutes of Health Stroke Scale (NIHSS).

PMID- 24856950
TI  - Further investigations of the donor-flight response.

PMID- 24856951
TI  - Distinguishing nontuberculous mycobacteria from multidrug-resistant Mycobacterium
      tuberculosis, China.

PMID- 24856952
TI  - Role of neoadjuvant therapy in the multimodality treatment of older patients with
      pancreatic cancer.
AB  - BACKGROUND: A well-defined treatment strategy for elderly patients with
      resectable pancreatic cancer is lacking. Multiple reports have described highly
      selected older cancer patients who have successfully undergone pancreatectomy.
      However, multimodality therapy is essential for long-term survival, and elderly
      patients are at high risk for not receiving adjuvant therapy postoperatively. We
      sought to describe the treatment patterns and outcomes of a series of elderly
      patients with pancreatic cancer who were treated with a multimodality strategy
      that liberally used neoadjuvant therapy. STUDY DESIGN: We retrospectively
      reviewed treatment plans, short-term outcomes, and overall survival of all
      patients 70 years old and older, presenting to our institution over a 9-year
      period, who were treated for potentially resectable or borderline resectable
      pancreatic cancer. RESULTS: There were 179 (76%) of 236 patients treated with
      curative intent. Of these patients, 153 (85%) initiated neoadjuvant therapy: 74
      (48%) subsequently underwent pancreatectomy and 79 did not due to disease
      progression (n = 46), insufficient performance status (n = 23), or other reasons
      (n = 10). Eleven (42%) of 26 patients who underwent surgery first received
      postoperative therapy. Among patients treated with curative intent, the median
      overall survival of all patients initiating neoadjuvant therapy (16.6 months
      [range 2.1 to 142.7 months]) was similar to that of patients undergoing resection
      primarily (15.1 months [range 5.4 to 100.8 months]), p = 0.53. After
      pancreatectomy, patients had a 2% in-hospital mortality rate and 91% were
      discharged home. CONCLUSIONS: Eighty-five percent of all patients 70 years old
      and older, who underwent pancreatectomy for potentially resectable or borderline
      resectable pancreatic cancer, received multimodality therapy. More than 90% were
      discharged home. These data demonstrate a potential role for neoadjuvant therapy
      in selecting elderly patients for surgery, and support further studies to refine
      individualized treatment protocols for this high-risk population.

PMID- 24856953
TI  - Treatment of osteochondroma in the mandibular condyle and secondary dentofacial
      deformities using surgery combined with orthodontics in adults.
AB  - PURPOSE: Osteochondroma is a benign tumor that is rare in the craniofacial
      region. When it does occur, the condyle and coronoid process have been the most
      commonly affected sites. The secondary progressive malocclusion and facial
      asymmetry will be common physical signs in most cases. The traditional surgical
      treatment of osteochondroma of the mandibular condyle has been condylectomy, with
      or without reconstruction of the condyle. We believe more attention should be
      paid to restoring joint function, improving the facial appearance, correcting
      malocclusion, and re-establishing harmony among them. PATIENTS AND METHODS: From
      January 2000 to March 2013, 27 patients (17 women and 10 men) who had been
      diagnosed with osteochondroma of a unilateral mandibular condyle underwent
      condylectomy and condylar reconstruction using a pedicled posterior mandibular
      border obtained by ramus osteotomy. The secondary dentofacial deformities were
      simultaneously corrected using orthognathic and facial contouring procedures,
      followed by orthodontic treatment, when necessary. Occlusion and
      temporomandibular joint pain and function, including the maximal mouth opening
      and maximal protrusion, were recorded preoperatively and postoperatively.
      RESULTS: The patients were followed for an average of 13 months (range 24 to 48).
      The outcomes of, and feedback information from the patients showed apparent
      improved joint function, with no cases of osteochondroma recurrence. The
      secondary dentofacial deformities were corrected significantly. Satisfactory
      occlusion was achieved with orthognathic and orthodontic treatment. CONCLUSIONS:
      Our data suggest that condylectomy and condylar reconstruction, with simultaneous
      correction of the secondary dentofacial deformities using orthognathic
      procedures, might be a better approach to manage osteochondroma accompanied by
      dentofacial deformities. In addition to facial contouring procedures, orthodontic
      treatment should be considered for better improvement in facial esthetics and
      occlusion.

PMID- 24856954
TI  - Gelatin hydrogel as a carrier of recombinant human fibroblast growth factor-2
      during rat mandibular distraction.
AB  - PURPOSE: The aim of the present study was to evaluate the feasibility of a
      gelatin hydrogel system to enhance recombinant human fibroblast growth factor-2
      (rhFGF-2)-induced osteogenic effects during rat mandibular distraction. MATERIALS
      AND METHODS: Mandibular distraction was performed in 28 male Wistar rats. Then,
      the rats were divided into 5 groups in which the designated gel mix was inserted
      into the distracted area: group 1, rhFGF-2 alone (n = 5); group 2, collagen alone
      (n = 6); group 3, collagen incorporating rhFGF-2 (n = 6); group 4, gelatin
      hydrogel alone (n = 5); and group 5, gelatin hydrogel incorporating rhFGF-2 (n =
      6). The mandibles were excised 29 days after surgery and the newly formed bone
      was analyzed radiologically and histologically. The experimental groups were
      compared using the Fisher post hoc test (95% statistical significance threshold;
      P < .05). RESULTS: Peripheral quantitative computed tomographic analysis, von
      Kossa staining, and calcein staining showed that using gelatin hydrogel with
      rhFGF-2 (group 5) significantly increased cortical bone mineral density, the
      domain area of hard tissue, the domain area of cortical bone area, total bone
      mineral content, cortical bone mineral content, the von Kossa-stained area, and
      the calcein-stained area compared with the collagen carrier (group 3). Group 5
      also had a significantly larger number of cells positive for tartrate-resistant
      acid phosphatase compared with group 3 and radiopaque areas were observed more
      frequently. CONCLUSIONS: The present findings suggest that gelatin hydrogel is a
      feasible delivery system for rhFGF-2, and when used together perform better in
      regard to hard tissue healing and treatment time after surgery.

PMID- 24856955
TI  - Recording of natural head position using stereophotogrammetry: a new technique
      and reliability study.
AB  - The purpose of this study was to develop a technique to record physical
      references and orient digital mesh models to a natural head position using
      stereophotogrammetry (SP). The first step was to record the digital mesh model of
      a hanging reference board placed at the capturing position of the SP machine. The
      board was aligned to true vertical using a plumb bob. It also was aligned with a
      laser plane parallel to a hanging mirror, which was located at the center of the
      machine. The parameter derived from the digital mesh model of the board was used
      to adjust the roll, pitch, and yaw of the subsequent captures of patients' facial
      images. This information was valid until the next machine calibration. The board
      placement was repeatable, with standard deviations less than 0.1 degrees  for
      pitch and yaw angles and 0.15 degrees  for roll angles. 

PMID- 24856956
TI  - External root resorption of the second molar associated with third molar
      impaction: comparison of panoramic radiography and cone beam computed tomography.
AB  - PURPOSE: The aim of the present study was to compare panoramic radiography and
      cone beam computed tomography (CBCT) for the assessment of external root
      resorption (ERR) of second molars associated with impacted third molars. In
      addition, the prevalence of ERR in second molars and the inclinations of the
      third molars more associated with ERR were investigated in both imaging methods.
      MATERIALS AND METHODS: The sample consisted of 66 individuals with maxillary and
      mandibular impacted third molars (n = 188) seen on panoramic radiographs and CBCT
      images. The presence of ERR on the adjacent second molar was investigated, and
      the position of the third molar was determined using Winter's classification
      (vertical, horizontal, mesioangular, distoangular, and transverse). Statistical
      analysis was performed using the chi(2) test, Fisher exact test, and 2-proportion
      Z test (the significance level was set at 5%). RESULTS: A significantly greater
      number of cases of ERR (P < .0001) was diagnosed from CBCT images (n = 43,
      22.88%) than panoramic radiographs (n = 10, 5.31%). The agreement between the
      panoramic radiographs and CBCT scans for diagnosing ERR was 4.3%. Mandibular
      third molars in mesioangular and horizontal inclinations were more likely to
      cause resorption of the adjacent teeth. CONCLUSIONS: CBCT should be indicated for
      the diagnosis of ERR in second molars when direct contact between the mandibular
      second and third molars has been observed on panoramic radiographs, especially in
      mesioangular or horizontal impactions. Furthermore, considering the propensity of
      these teeth to cause ERR in second molars, third molar prophylactic extraction
      could be suggested.

PMID- 24856957
TI  - Mixed fuel strategy for carbon deposition mitigation in solid oxide fuel cells at
      intermediate temperatures.
AB  - In this study, we propose and experimentally verified that methane and formic
      acid mixed fuel can be employed to sustain solid oxide fuel cells (SOFCs) to
      deliver high power outputs at intermediate temperatures and simultaneously reduce
      the coke formation over the anode catalyst. In this SOFC system, methane itself
      was one part of the fuel, but it also played as the carrier gas to deliver the
      formic acid to reach the anode chamber. On the other hand, the products from the
      thermal decomposition of formic acid helped to reduce the carbon deposition from
      methane cracking. In order to clarify the reaction pathways for carbon formation
      and elimination occurring in the anode chamber during the SOFC operation, O2-TPO
      and SEM analysis were carried out together with the theoretical calculation.
      Electrochemical tests demonstrated that stable and high power output at an
      intermediate temperature range was well-maintained with a peak power density of
      1061 mW cm(-2) at 750  degrees C. With the synergic functions provided by the
      mixed fuel, the SOFC was running for 3 days without any sign of cell performance
      decay. In sharp contrast, fuelled by pure methane and tested at similar
      conditions, the SOFC immediately failed after running for only 30 min due to
      significant carbon deposition. This work opens a new way for SOFC to conquer the
      annoying problem of carbon deposition just by properly selecting the fuel
      components to realize their synergic effects. 

PMID- 24856958
TI  - Electroacupuncture Promotes the Differentiation of Transplanted Bone Marrow
      Mesenchymal Stem Cells Preinduced With Neurotrophin-3 and Retinoic Acid Into
      Oligodendrocyte-Like Cells in Demyelinated Spinal Cord of Rats.
AB  - Transplantation of bone marrow mesenchymal stem cells (MSCs) promotes functional
      recovery in multiple sclerosis (MS) patients and in a murine model of MS.
      However, there is only a modicum of information on differentiation of grafted
      MSCs into oligodendrocyte-like cells in MS. The purpose of this study was to
      transplant neurotrophin-3 (NT-3) and retinoic acid (RA) preinduced MSCs (NR-MSCs)
      into a demyelinated spinal cord induced by ethidium bromide and to investigate
      whether EA treatment could promote NT-3 secretion in the demyelinated spinal
      cord. We also sought to determine whether increased NT-3 could further enhance NR
      MSCs overexpressing the tyrosine receptor kinase C (TrkC) to differentiate into
      more oligodendrocyte-like cells, resulting in increased remyelination and nerve
      conduction in the spinal cord. Our results showed that NT-3 and RA increased
      transcription of TrkC mRNA in cultured MSCs. EA increased NT-3 levels and
      promoted differentiation of oligodendrocyte-like cells from grafted NR-MSCs in
      the demyelinated spinal cord. There was evidence of myelin formation by grafted
      NR-MSCs. In addition, NR-MSC transplantation combined with EA treatment (the NR
      MSCs + EA group) reduced demyelination and promoted remyelination. Furthermore,
      the conduction of cortical motor-evoked potentials has improved compared to
      controls. Together, our data suggest that preinduced MSC transplantation combined
      with EA treatment not only increased MSC differentiation into oligodendrocyte
      like cells forming myelin sheaths, but also promoted remyelination and functional
      improvement of nerve conduction in the demyelinated spinal cord. 

PMID- 24856960
TI  - Controlled-release drug delivery system based on fluocinolone acetonide
      cyclodextrin inclusion complex incorporated in multivesicular liposomes.
AB  - Abstract Multivesicular liposomes (MVLs) have been widely studied for
      encapsulation of hydrophilic drugs due to their structural properties and large
      aqueous inner cavities. In this study, to investigate MVLs and their potential
      application for incorporation of hydrophobic drugs, new drug delivery system for
      fluocinolone acetonide (FA), as a lipophilic model drug, was developed combining
      the advantages of cyclodextrin inclusion complexes (CD-IC) and multivesicular
      liposomes. FA was complexed with several CDs to form inclusion complex (FA-CD-IC)
      and then FA-CD-IC was incorporated into MVLs by reverse-phase evaporation method.
      Physicochemical characterization of drug-CD-IC, at a molar ratio of 1:1 (drug to
      CD) was studied using 1HNMR, FT-IR, DSC and UV spectroscopy. The influence of
      various types of CDs on the aqueous solubility of FA, encapsulation efficiency
      and release profile in MVLs was studied. The results revealed the formation of
      inclusion complexes between the drug and CDs. Both the CD's type and proportion
      played an important role in the physicochemical properties of the systems. The
      inclusion complex of the drug with hydroxypropyl-beta-cyclodextrin exhibited the
      most appropriate loading and sustained-release profile over prolonged periods.
      The results reveal the promising potential of MVLs as a stable drug delivery
      system to release the drug in a sustained manner for the treatment of ocular
      inflammatory disease.

PMID- 24856959
TI  - Force-controlled manipulation of single cells: from AFM to FluidFM.
AB  - The ability to perturb individual cells and to obtain information at the single
      cell level is of central importance for addressing numerous biological questions.
      Atomic force microscopy (AFM) offers great potential for this prospering field.
      Traditionally used as an imaging tool, more recent developments have extended the
      variety of cell-manipulation protocols. Fluidic force microscopy (FluidFM)
      combines AFM with microfluidics via microchanneled cantilevers with nano-sized
      apertures. The crucial element of the technology is the connection of the hollow
      cantilevers to a pressure controller, allowing their operation in liquid as force
      controlled nanopipettes under optical control. Proof-of-concept studies
      demonstrated a broad spectrum of single-cell applications including isolation,
      deposition, adhesion and injection in a range of biological systems.

PMID- 24856961
TI  - Statistical optimization of controlled release microspheres containing cetirizine
      hydrochloride as a model for water soluble drugs.
AB  - The purpose was to improve the encapsulation efficiency of cetirizine
      hydrochloride (CTZ) microspheres as a model for water soluble drugs and control
      its release by applying response surface methodology. A 3(3) Box-Behnken design
      was used to determine the effect of drug/polymer ratio (X1), surfactant
      concentration (X2) and stirring speed (X3), on the mean particle size (Y1),
      percentage encapsulation efficiency (Y2) and cumulative percent drug released for
      12 h (Y3). Emulsion solvent evaporation (ESE) technique was applied utilizing
      Eudragit RS100 as coating polymer and span 80 as surfactant. All formulations
      were evaluated for micromeritic properties and morphologically characterized by
      scanning electron microscopy (SEM). The relative bioavailability of the optimized
      microspheres was compared with CTZ marketed product after oral administration on
      healthy human volunteers using a double blind, randomized, cross-over design. The
      results revealed that the mean particle sizes of the microspheres ranged from 62
      to 348 um and the efficiency of entrapment ranged from 36.3% to 70.1%. The
      optimized CTZ microspheres exhibited a slow and controlled release over 12 h. The
      pharmacokinetic data of optimized CTZ microspheres showed prolonged tmax,
      decreased Cmax and AUC0-infinity value of 3309 +/- 211 ng h/ml indicating
      improved relative bioavailability by 169.4% compared with marketed tablets. 

PMID- 24856965
TI  - Identification of halogenated photoproducts generated after ultraviolet
      irradiation of parabens and benzoates in water containing chlorine by solid-phase
      microextraction and gas chromatography-mass spectrometry.
AB  - This work presents a new solid-phase microextraction (SPME)-based approach to
      investigate the formation of halogenated by-products generated by the UV-induced
      photodegradation of parabens and their congener benzoates in water containing
      chlorine. Degradation of parent species, and further identification of their
      transformation by-products were monitored by gas chromatography coupled to mass
      spectrometry (GC/MS). In order to improve detectability, SPME was applied as a
      preconcentration step after UV-irradiation of target preservatives. Experiments
      performed with dechlorinated water, ultrapure water, and tap water showed that
      under UV-light, the presence of even low levels of free chlorine, increases the
      photodegradation rate of target preservatives, enhancing the formation of
      halogenated photoproducts. Monobrominated, dibrominated and bromochlorinated
      hydroxybenzoates were identified, and the transformation of benzoates into
      halogenated parabens was also confirmed. Bromination is expected to occur when
      free chlorine is present, due to the presence of traces of bromide in water
      samples. Five halogenated phenols (mainly brominated) were detected as breakdown
      photoproducts from both families of target preservatives. On the basis of the
      appearance of the aforementioned by-products, a tentative transformation pathway,
      consistent with the photoformation-photodecay kinetics of the by-products, is
      proposed herein for the first time. 

PMID- 24856966
TI  - High-sensitivity analysis of anionic sulfonamides by capillary electrophoresis
      using a synergistic stacking approach.
AB  - A synergistic stacking approach whereby field-enhanced sample injection and
      micelle-to-solvent stacking in capillary zone electrophoresis are combined has
      been developed and has been applied to the separation and quantification of
      anionic sulfonamides. Electrokinetic injection of the sample in a low
      conductivity alkaline diluent was performed for 90s at -15kV. Micelle-to-solvent
      stacking was then undertaken by hydrodynamic injection of micellar
      cetyltrimethylammonium bromide solution prior to the electrokinetic injection of
      sample that also contained 50% methanol. This combined stacking approach, when
      compared to a typical hydrostatic injection, provided improvements in peak height
      and corrected peak area in the range of 397-1024 and 758-1246, respectively.
      Limits of quantification in the range of 0.01-0.03MUg/mL were obtained for
      sulfamerazine, sulfamethazine and sulfamethizole and were sufficient for the
      determination of these analytes in river water. The percentage recovery and
      accuracy values obtained for a fortified river water sample that had been
      subjected to sample preparation by evaporation and reconstitution with diluent
      were 74-135%. Intra-day and inter-day repeatabilities for migration time, peak
      height, and corrected peak area were in the range 0.5-5.0% (percentage relative
      standard deviation, n=8) and these relatively low values were attributed to the
      use of a stable capillary coating established by the successive multiple ionic
      polymer layer technique. 

PMID- 24856967
TI  - Adamantyl-group containing mixed-mode acrylamide-based continuous beds for
      capillary electrochromatography. Part IV: investigation of the chromatographic
      efficiency dependent on the retention mode.
AB  - In our previous work we have described the synthesis, characterization, and
      optimization of the chromatographic efficiency of a highly crosslinked
      macroporous mixed-mode acrylamide-based monolithic stationary phase synthesized
      by in situ free radical copolymerization of cyclodextrin-solubilized N-adamantyl
      acrylamide, piperazinediacrylamide, methacrylamide and vinylsulfonic acid in
      aqueous medium in pre-treated fused silica capillaries of 100MUm I.D. In the
      present work, we study with different classes of neutral analytes (with varied
      hydrophobicity) the impact of the type of retention mode (influenced by the type
      of analyte and the mobile phase composition) and the impact of the solute
      functionality on the chromatographic efficiency and peak symmetry with a monolith
      synthesized under optimized synthesis parameters. With this monolithic capillary
      high separation efficiencies (up to ca. 220,000m(-1)) are obtained for the
      separation of different analyte classes (alkylphenones, nitrotoluenes, and
      phenolic compounds with k=0.2-0.55) in the reversed-phase mode, in the normal
      phase mode, and in the mixed mode. For neutral alkylanilines (k<0.25) plate
      numbers of about 300,000m(-1) are routinely reached in the reversed-phase elution
      mode. For phenolic solutes separated in a mixed mode there is a solute-specific
      influence on peak symmetry and chromatographic efficiency. With increasing
      efficiency of the monolith, axial diffusion becomes an important mechanism of
      band broadening. For those peaks, which do not show a significant asymmetry
      (asymmetry factor <=1.05), it is confirmed that plate heights gained via the
      tangent method are equivalent to those gained via moment analysis. 

PMID- 24856968
TI  - Multi-residue analysis of pharmaceuticals in aqueous environmental samples by
      online solid-phase extraction-ultra-high-performance liquid chromatography-tandem
      mass spectrometry: optimisation and matrix effects reduction by quick, easy,
      cheap, effective, rugged and safe extraction.
AB  - The aim of this study was to develop and optimise an analytical method for the
      quantification of a bactericide and 13 pharmaceutical products, including 8
      antibiotics (fluoroquinolones, tetracyclines, sulfonamides, macrolide), in
      various aqueous environmental samples: soil water and aqueous fractions of pig
      slurry, digested pig slurry and sewage sludge. The analysis was performed by
      online solid-phase extraction coupled to ultra-high performance liquid
      chromatography with tandem mass spectrometry (online SPE-UHPLC-MS-MS). The main
      challenge was to minimize the matrix effects observed in mass spectrometry,
      mostly due to ion suppression. They depended on the dissolved organic carbon
      (DOC) content and its origin, and ranged between -22% and +20% and between -38%
      and -93% of the signal obtained without matrix, in soil water and slurry
      supernatant, respectively. The very variable levels of these matrix effects
      suggested DOC content cut-offs above which sample purification was required.
      These cut-offs depended on compounds, with concentrations ranging from 30 to
      290mgC/L for antibiotics (except tylosine) up to 600-6400mgC/L for the most
      apolar compounds. A modified Quick, Easy, Cheap, Effective, Rugged and Safe
      (QuEChERS) extraction procedure was therefore optimised using an experimental
      design methodology, in order to purify samples with high DOC contents. Its
      performance led to a compromise, allowing fluoroquinolone and tetracycline
      analysis. The QuEChERS extraction salts consisted therefore of sodium acetate,
      sodium sulfate instead of magnesium sulfate, and sodium
      ethylenediaminetetraacetate (EDTA) as a ligand of divalent cations. The modified
      QuEChERS procedure employed for the extraction of pharmaceuticals in slurry and
      digested slurry liquid phases reduced the matrix effects for almost all the
      compounds, with extraction recoveries generally above 75%. The performance
      characteristics of the method were evaluated in terms of linearity, intra-day and
      inter-day precision, accuracy and limits of quantification, which reached
      concentration ranges of 5-270ng/L in soil water and sludge supernatant, and 31
      2400ng/L in slurry and digested slurry supernatants, depending on the compounds.
      The new method was then successfully applied for the determination of the target
      compounds in environmental samples. 

PMID- 24856969
TI  - A monoclonal antibody that targets a NaV1.7 channel voltage sensor for pain and
      itch relief.
AB  - Voltage-gated sodium (NaV) channels control the upstroke of the action potentials
      in excitable cells. Multiple studies have shown distinct roles of NaV channel
      subtypes in human physiology and diseases, but subtype-specific therapeutics are
      lacking and the current efforts have been limited to small molecules. Here, we
      present a monoclonal antibody that targets the voltage-sensor paddle of NaV1.7,
      the subtype critical for pain sensation. This antibody not only inhibits NaV1.7
      with high selectivity, but also effectively suppresses inflammatory and
      neuropathic pain in mice. Interestingly, the antibody inhibits acute and chronic
      itch despite well-documented differences in pain and itch modulation. Using this
      antibody, we discovered that NaV1.7 plays a key role in spinal cord nociceptive
      and pruriceptive synaptic transmission. Our studies reveal that NaV1.7 is a
      target for itch management, and the antibody has therapeutic potential for
      suppressing pain and itch. Our antibody strategy may have broad applications for
      voltage-gated cation channels.

PMID- 24856971
TI  - Investigation of knowledge of asthma and inhaler devices in pharmacy workers.
AB  - OBJECTIVE: Effective management of asthma requires the development of a
      partnership between the patient and his or her health care professionals. In a
      number of countries, including Turkey, pharmacy workers are the last link in the
      asthma therapy chain and usually give information to their patients about the use
      of these drugs and asthma. As a result, we investigated knowledge of asthma and
      the use of inhaler devices in pharmacy workers in Istanbul pharmacies. METHODS:
      The study was performed with 266 pharmacists and 261 pharmacist assistants
      selected from 4221 pharmacies in Istanbul by random sampling, with a 90%
      confidence interval. Each patient was asked to fill out a questionnaire that
      measured their knowledge of asthma. They were also asked to demonstrate how to
      use the inhaler devices. RESULTS: The high number of incorrect answers to the
      11th question, that ''the majority of upper respiratory tract infections
      triggering asthma are viral'', may be a contributor to the unnecessary use of
      antibiotics in Turkey (incorrect answers from 41.2% of pharmacists and 34.5% of
      pharmacist assistants). Scores for inhalation device techniques for the
      pharmacists were as follows: metered-dose inhaler (MDI), 4.9 +/- 3.9; discus, 4.4
      +/- 3.7; aerolizer, 4 +/- 3.1; and turbuhaler, 3.8 +/- 2.9. CONCLUSIONS: Istanbul
      pharmacy workers have limited knowledge about asthma and inhaler devices and need
      further education, which may contribute to improved asthma control in Turkey.

PMID- 24856970
TI  - Variant PRC1 complex-dependent H2A ubiquitylation drives PRC2 recruitment and
      polycomb domain formation.
AB  - Chromatin modifying activities inherent to polycomb repressive complexes PRC1 and
      PRC2 play an essential role in gene regulation, cellular differentiation, and
      development. However, the mechanisms by which these complexes recognize their
      target sites and function together to form repressive chromatin domains remain
      poorly understood. Recruitment of PRC1 to target sites has been proposed to occur
      through a hierarchical process, dependent on prior nucleation of PRC2 and
      placement of H3K27me3. Here, using a de novo targeting assay in mouse embryonic
      stem cells we unexpectedly discover that PRC1-dependent H2AK119ub1 leads to
      recruitment of PRC2 and H3K27me3 to effectively initiate a polycomb domain. This
      activity is restricted to variant PRC1 complexes, and genetic ablation
      experiments reveal that targeting of the variant PCGF1/PRC1 complex by KDM2B to
      CpG islands is required for normal polycomb domain formation and mouse
      development. These observations provide a surprising PRC1-dependent logic for
      PRC2 occupancy at target sites in vivo.

PMID- 24856973
TI  - Influence of open testicular biopsy in prepubertal rats on rats' adulthood
      fertility with correlation to serum levels of inhibin B and follicle stimulating
      hormone.
AB  - OBJECTIVE: Open testicular biopsy (OTB) is one of the options to accurately
      assess fertility potential of the undescended testis. The aim of the study was to
      investigate consequences of OTB in prepubertal rats on their adulthood fertility.
      METHODS: Thirty-eight prepubertal male rats were divided into three groups
      depending on day 20 procedure. The first group was the control group, the second
      sham operated and the third has left OTB. Bilateral orchiectomy was performed on
      day 70 to all groups, with determination of serum inhibin B and follicle
      stimulating hormone (FSH). Removed testes were compared according to the weight,
      volume, spermatogenesis, histological and apoptotic changes in both testes with
      differences in serum levels of inhibin B and FSH. RESULTS: Ipsilateral testicular
      weight, volume, and spermatogenesis reduction with a reduction of tubular number,
      diameter and germinative epithelium was found in OTB group. Significant increase
      in apoptotic index was found in biopsied testis without compensatory hypertrophy
      of contralateral testis. Differences of inhibin B and FSH were not statistically
      significant among three groups. CONCLUSION: OTB in prepubertal rats has
      detrimental effects on fertility in adulthood. It does not cause compensatory
      hypertrophy of the contralateral testis nor does it disturb serum levels of
      inhibin B and FSH.

PMID- 24856974
TI  - An analysis of long-term occurrence of renal complications following pediatric
      pyeloplasty.
AB  - OBJECTIVE: Few reports discuss post-pubertal renal complications after
      pyeloplasty. We analyzed long-term complications, such as decreased renal
      function (RF) measured by serum creatinine (SCr), hypertension (HTN), or
      proteinuria (protU) following pediatric pyeloplasty. SUBJECTS AND METHODS: We
      retrospectively investigated 257 patients who underwent dismembered pyeloplasty
      due to ureteropelvic junction obstruction from January 1986 to December 2001.
      Medical history, preoperative and postoperative blood pressure, urinalysis, and
      SCr results were reviewed. RESULTS: Fifty-five patients (47 male, 8 female) who
      were followed up for at least 10 years with post-pubertal follow-up data
      available were analyzed. Seven (12.7%) patients were diagnosed with HTN, and 10
      (18.2%) with protU. The grade of hydronephrosis decreased, and the differential
      RF measured by MAG-3 renal scan significantly increased at final analysis
      (p<0.001). Presence of preoperative symptoms (p=0.034), and SCr elevation
      (p=0.018) showed correlation with HTN. HTN took 15.7 (+/-5.8) (7-25) years, and
      protU detection took 16.2 (+/-5.9) (6-23) years, with the highest incidence of
      both HTN and protU between 15 and 20 years postoperatively. CONCLUSION: According
      to our investigation, a prudent evaluation of signs of RF decrease at 10 years
      after surgery, and then every 5 years, until 20 years should be recommended,
      although further studies are necessary.

PMID- 24856976
TI  - B-lymphoblastic leukemia/lymphoma: overexpression of nuclear DNA repair protein
      PARP-1 correlates with antiapoptotic protein Bcl-2 and complex chromosomal
      abnormalities.
AB  - Poly(ADP-ribose) polymerase-1 (PARP-1) and Bcl-2 are emerging as therapeutic
      targets in various cancers. The former is a DNA repair protein associated with
      genomic stability and apoptosis, whereas the latter is an antiapoptotic protein
      having a DNA repair function through inhibition of PARP-1. Because genomic
      stability is critical for prognosis in B-lymphoblastic leukemia/lymphoma (B-ALL),
      we studied the expression of PARP-1 and Bcl-2 proteins in patients with B-ALL of
      different ages and compared the results with cytogenetic data. The PARP-1 protein
      was overexpressed in about two-thirds (61%) of patients with B-ALL. It had a
      nuclear location, whereas Bcl-2 protein was cytosolic. Expression of the 2
      proteins showed a highly positive correlation (rho = 0.367; P < .001).
      Overexpression of PARP-1 correlated with a complex karyotype (P = .030), and this
      correlation remained significant for coexpression of PARP-1 and Bcl-2 proteins
      (chi(2) = 7.498; P = .024) as well as after exclusion of pediatric patients (n =
      9, P = .042). Overexpression of PARP-1 was not significantly more common in
      diploid versus aneuploid karyotypes (50% versus 59%, P = .610). The PARP-1
      protein showed no correlation with specific chromosomal abnormalities associated
      with prognosis in B-ALL, as defined by the World Health Organization. In
      conclusion, high expression of the PARP-1 protein among patients with B-ALL is
      related to a complex karyotype and Bcl-2 positivity. Although these findings
      require validation in a larger population, the observations will be valuable in
      planning therapeutic trials (such as of PARP inhibitors and BH3 mimetics).

PMID- 24856977
TI  - Comparative analysis of comorbidity and performance indices for prediction of
      oncological outcomes in patients with upper tract urothelial carcinoma who were
      treated with radical nephroureterectomy.
AB  - OBJECTIVE: Comorbidity and performance indices (CPIs) are useful tools to
      evaluate patient's risk of comorbidities and thus may guide clinical decision
      making regarding surgery or multimodal therapy approaches. Hence, the aim of the
      current study was to assess the predictive capacity of CPIs comprising the
      American Society of Anaesthesiologists (ASA)-score, the Charlson comorbidity
      index (CCI), the age-adjusted CCI (ACCI), and the Eastern Cooperative Oncology
      Group performance status (ECOG-PS) in patients with upper tract urothelial
      carcinoma (UTUC) who were treated with radical nephroureterectomy (RNU). METHODS
      AND MATERIALS: A total of 242 patients with UTUC underwent RNU without
      neoadjuvant chemotherapy between 1992 and 2012 at 3 German academic centers.
      Patients were stratified according to the pre-RNU CPIs dichotomized as ASA 1/2 vs
      .>= 3, CCI 0 to 2 vs. > 2, ACCI 0 to 5 vs. > 5, and ECOG-PS 0 to 1 vs. > 1. We
      assessed the associations of CPIs with clinicopathologic features, as well as the
      prognostic effect on recurrence-free survival, cancer-specific survival (CSS),
      overall survival, and cancer-independent mortality (CIM), using univariable and
      multivariable Cox regression analyses. RESULTS: Sixty-two patients (25.6%) had an
      ASA-score >= 3, 71 patients (29.3%) a CCI>2, 50 patients (20.7%) an ACCI > 5, and
      122 (50.4%) patients an ECOG-PS > 1. The ASA-score (P = 0.001), CCI (P = 0.029),
      and the ECOG-PS (P < 0.001) were significantly associated with age. In addition,
      the ECOG-PS was associated with pelvicalyceal tumors (P = 0.012), and the CCI
      with preoperative hydronephrosis (P = 0.026). The median follow-up was 30 months.
      In Kaplan-Meier analyses, ACCI > 5 (P <= 0.025) and ECOG-PS > 1 (P <= 0.042) were
      associated with recurrence-free survival, CSS, and overall survival, and ASA
      score >= 3 (P = 0.011) and ACCI > 5 (P = 0.006) with CIM. In multivariable
      analysis that adjusted for standard clinicopathologic parameters, an ECOG-PS > 1
      was an independent predictor for CSS (hazard ratio = 1.89, P = 0.019), and an ASA
      score >= 3 (hazard ratio = 1.86, P = 0.026) was a predictor for CIM. CONCLUSION:
      CPIs are easy assessable predictors for outcome in patients with UTUC who were
      treated with RNU. CPIs have carefully to be taken into account in patient
      counseling regarding operative decision making and multimodal treatment.

PMID- 24856978
TI  - Risk factors for bladder cancer recurrence after nephroureterectomy for upper
      tract urothelial tumors: results from the Canadian Upper Tract Collaboration.
AB  - OBJECTIVE: To evaluate risk factors for bladder cancer recurrence in a cohort of
      patients treated with radical nephroureterectomy (RNU). PATIENTS AND METHODS: At
      10 Canadian University Centers, we retrospectively evaluated data, between 1990
      and 2010, from 743 patients who were free from bladder cancer and were previously
      treated with RNU for upper tract urothelial cancer. RESULTS: Of 743 patients, 167
      (22.5%) developed bladder tumors after a median time of 17.2 months after RNU.
      Multivariable analysis detected age (hazard ratio [HR] = 1.028; 95% CI: 1.010
      1.046; P = 0.0018), tumor location in both the renal pelvis and the ureter (HR =
      2.205; 95% CI: 1.355-3.589; P = 0.0015), the use of adjuvant systemic
      chemotherapy (HR = 2.309; 95% CI: 1.439-3.705; P = 0.0005), and laparoscopic
      surgery (HR = 1.876; 95% CI: 1.226-2.87; P = 0.0037) as risk factors for bladder
      cancer recurrence. Open excision of a bladder cuff (HR = 0.661; 95% CI: 0.453
      0.965; P = 0.0319) and transurethral resection of the intramural ureter (HR =
      0.548; 95% CI: 0.306-0.981; P = 0.0429) on comparison with extravesical resection
      decreased the risk of bladder cancer recurrence significantly. Major limitations
      were the retrospective design and partially missing data, although the
      significance of variables did not change in the imputation analysis. CONCLUSION:
      Older patients, those with tumor location in both the renal pelvis and the
      ureter, and those treated with adjuvant systemic chemotherapy were found at
      higher risk for intravesical recurrence, as were those having undergone
      extravesical ureterectomy or laparoscopic RNU.

PMID- 24856979
TI  - Short-term morbidity and mortality of Indiana pouch, ileal conduit, and
      neobladder urinary diversion following radical cystectomy.
AB  - PURPOSE: Literature surrounding Indiana pouch (IP) urinary diversion suggests a
      higher incidence of complications and longer operative time compared with ileal
      conduit (IC) and neobladder (NB). We sought to assess short-term complications of
      IP diversions compared with other diversions at our institution. MATERIALS AND
      METHODS: Using institutional National Surgical Quality Improvement Program data,
      we identified radical cystectomy cases performed for bladder cancer at Indiana
      University from January 2011 until June 2013. During this time period, the
      National Surgical Quality Improvement Program randomly evaluated approximately
      70% of radical cystectomies performed for urothelial carcinoma at our
      institution. Multivariable logistic regression was performed to identify factors
      associated with Clavien grade III-V complications. RESULTS: A total of 233 cases
      were identified, 139 IC, 39 IP, and 55 NB. Mean (standard deviation) operative
      times for IC, IP, and NB were 257 (84), 383 (78), and 327 (88) minutes,
      respectively (P<0.001). Half of the patients required blood transfusion during
      the hospitalization. The overall rate of complications was significantly lower
      among NB (P = 0.009). Overall, 12% of patients developed a Clavien grade III-V
      complication, with no difference observed between groups (P = 0.884). After
      controlling for preoperative confounders, IP patients were not at increased odds
      of developing a Clavien III-V complication compared with IC (odds ratio = 1.38, P
      = 0.599). CONCLUSIONS: At a high-volume center, the incidence of serious
      complications was similar between diversion types. IP patients were more likely
      to experience minor complications. Patients should be counseled regarding rates
      of short-term complications and blood transfusion.

PMID- 24856980
TI  - Validation of Surveillance, Epidemiology, and End Results TNM staging for
      testicular germ cell tumor.
AB  - OBJECTIVES: To evaluate the accuracy of testicular germ cell tumor category in
      the Surveillance, Epidemiology, and End Results (SEER) database following the
      2010 American Joint Committee of Cancer revision of the TNM staging criteria.
      METHODS: We performed a retrospective review of our testicular cancer database
      from January 2010 to July 2011. Registrar extracted data on 76 patients were
      entered into the Cancer Surveillance Program database from 2 hospitals. We
      reviewed the SEER coding for each patient, including T, N, M, and S and overall
      stage group, as well as the range and S value given for tumor markers (lactate
      dehydrogenase, beta-human chorionic gonadotropin, and alpha-fetoprotein) both
      preorchiectomy and postorchiectomy. We then compared these values with the actual
      staging and tumor markers determined by patient medical record review by a single
      urologist. RESULTS: A high proportion of registry records were found to have
      inaccurate values of category: 71% of S category entries and 34% of N category
      entries, leading to an overall group stage inaccuracy of 77% in SEER data.
      Accuracy of overall combined stage group was significantly different between
      hospitals, with a higher percentage of errors at Hospital A (P< 0.05).
      CONCLUSION: Despite improvements made to the SEER criteria for extracting data
      used to code testicular germ cell tumor TNM stage, considerable errors were
      identified, most notably in tumor marker and nodal status, resulting in an
      overwhelming number of errors in overall stage. Our findings suggest caution when
      utilizing SEER data for review of patients with testicular cancer and their
      staging.

PMID- 24856982
TI  - The use of healthcare services for mental health problems by middle-aged and
      older adults.
AB  - Although mental disorders occur commonly in later life, it has been reported that
      older adults are reluctant to seek help for their mental health problems. The
      purpose of this research study was to analyze the contact with healthcare
      professionals, self-perceived mental health problems and unmet needs, as reported
      by a nationally representative sample of community-dwelling adults. We report a
      cross-sectional analysis of all the respondents of the Australian National Survey
      of Mental Health and Wellbeing aged 55 years and older (N=3178). Results
      indicated that 306 (9.6%) participants had a DSM-IV classifiable mental disorder
      based on self-identified symptoms over the preceding 12 months. Of these, 146
      (48%) reported that they had not consulted a healthcare professional to deal with
      their mental health problems. Among those who consulted with a healthcare
      professional, the general practitioner was the main point of contact. Medication
      and psychotherapy/counseling were the most frequent form of help obtained.
      Informational and instrumental help, such as help to sort out practical problems
      and to look after oneself, were the most reported unmet needs. These results
      suggest a gap in the provision of healthcare services for mental health problems
      directed toward the specific needs of aging adults. The reported unmet needs
      might be met by increasing awareness amongst healthcare professionals regarding
      mental health problems in later stages of life and by improving the access of
      older people to the services commonly provided by multidisciplinary teams. 

PMID- 24856983
TI  - Short communication: determination of lactoferrin in Feta cheese whey with
      reversed-phase high-performance liquid chromatography.
AB  - In the current paper, a method is introduced to determine lactoferrin in sweet
      whey using reversed-phase HPLC without any pretreatment of the samples or use of
      a separation technique. As a starting point, the most common HPLC protocols for
      acid whey, which included pretreatment of the whey along with a sodium dodecyl
      sulfate-PAGE step, were tested. By skipping the pretreatment and the separation
      steps while altering the gradient profile, different chromatographs were obtained
      that proved to be equally efficient to determine lactoferrin. For this novel 1
      step reversed-phase HPLC method, repeatability was very high over a wide range of
      concentrations (1.88% intraday to 5.89% interday). The limit of detection was
      35.46MUg/mL [signal:noise ratio (S/N)=3], whereas the limit of quantification was
      50.86MUg/mL (S/N=10). Omitting the pretreatment step caused a degradation of the
      column's lifetime (to approximately 2,000 samples). As a result, the lactoferrin
      elution time changed, but neither the accuracy nor the separation ability of the
      method was significantly influenced. We observed that this degradation could be
      easily avoided or detained by centrifuging the samples to remove fat or by
      extensive cleaning of the column after every 5 samples. 

PMID- 24856984
TI  - Lactobacillus acidophilus modulates the virulence of Clostridium difficile.
AB  - Clostridium difficile is a spore-forming, toxin-producing, anaerobic bacterium
      that colonizes the human gastrointestinal tract. This pathogen causes antibiotic
      associated diarrhea and colitis in animals and humans. Antibiotic-associated
      diseases may be treated with probiotics, and interest is increasing in such uses
      of probiotics. This study investigated the effect of Lactobacillus strains on the
      quorum-sensing signals and toxin production of C. difficile. In addition, an in
      vivo experiment was designed to assess whether Lactobacillus acidophilus GP1B is
      able to control C. difficile-associated disease. Autoinducer-2 activity was
      measured for C. difficile using the Vibrio harveyi coupled bioluminescent assay.
      Cell extract (10MUg/mL) of L. acidophilus GP1B exhibited the highest inhibitory
      activity among 5 to 40MUg/mL cell-extract concentrations. Real-time PCR data
      indicated decreased transcriptional levels in luxS, tcdA, tcdB, and txeR genes in
      the presence of 10MUg/mL of cell extract of L. acidophilus GP1B. Survival rates
      at 5d for mice given the pathogen alone with L. acidophilus GP1B cell extract or
      L. acidophilus GP1B were 10, 70, and 80%, respectively. In addition, the lactic
      acid-produced L. acidophilus GP1B exhibits an inhibitory effect against the
      growth of C. difficile. Both the L. acidophilus GP1B and GP1B cell extract have
      significant antipathogenic effects on C. difficile. 

PMID- 24856985
TI  - Effects of level of social contact on dairy calf behavior and health.
AB  - Housing preweaned dairy calves in pairs rather than individually has been found
      to positively affect behavioral responses in novel social and environmental
      situations, but concerns have been raised that close contact among very young
      animals may impair their health. In previous studies, the level of social contact
      permitted in individual housing has been auditory, visual, or physical contact.
      It is unclear how these various levels of social contact compare with each other
      and to pair housing, when their effects on behavior and health are considered,
      and whether the timing of pair housing has an effect. To investigate this, 110
      Holstein calves (50 males, 60 females) in 11 blocks were paired according to
      birth date. Within 60h of birth, each pair of calves was allocated to 1 of 5
      treatments: individual housing with auditory contact (I), individual housing with
      auditory and visual contact (V), individual housing with auditory, visual, and
      tactile contact (T), pair housing (P), or individual housing with auditory and
      visual contact the first 2wk followed by pair housing (VP). At 6wk of age, calves
      were subjected to a social test and a novel environment test. In the social test,
      all pair-housed calves (P and VP) had a shorter latency to sniff an unfamiliar
      calf than did individually housed calves (I, V, and T), whereas calves with
      physical contact (T, P, and VP) sniffed the unfamiliar calf for longer than
      calves on the remaining treatments (I and V). In the novel environment test,
      calves with physical contact (T, P, and VP) had a lower heart rate, and more of
      these calves vocalized during the test compared with calves without physical
      contact (I and V). No effect of treatment was found for clinical scores, levels
      of the 5 most common pathogens in feces, or in development of serum antibodies
      against the 3 most common respiratory pathogens. Calves housed individually are
      more fearful of unfamiliar calves than are pair-housed calves. Contrary to common
      belief, the allowance of physical contact and pair housing had no effects on the
      health of the calves. 

PMID- 24856986
TI  - Effect of whey concentration on protein recovery in fresh ovine ricotta cheese.
AB  - Ricotta cheese, particularly the ovine type, is a typical Italian dairy product
      obtained by heat-coagulation of the proteins in whey. The aim of this work was to
      investigate the influence of whey protein concentration, obtained by
      ultrafiltration, on yield of fresh ovine ricotta cheese. Ricotta cheeses were
      obtained by thermocoagulation of mixtures with protein content of 1.56, 3.10,
      4.16, and 7.09g/100g from the mixing of skim whey and ultrafiltered skim whey. A
      fat-to-protein ratio of 1.1 (wt/wt) was obtained for all mixtures by adding fresh
      cream. The initial mixtures, as well as the final ricotta cheeses, were analyzed
      for their composition and by SDS-PAGE. Protein bands were quantified by
      QuantityOne software (Bio-Rad, Hercules, CA) and identified by liquid
      chromatography-tandem mass spectrometry. Significant differences in the
      composition of the ricotta cheese were observed depending on protein
      concentration. Particularly, ricotta cheese resulting from the mixture containing
      7.09g/100g of protein presented higher moisture (72.88+/-1.50g/100g) and protein
      (10.18+/-0.45g/100g) contents than that prepared from the mixture with 1.56g/100g
      of protein (69.52+/-1.75 and 6.70+/-0.85g/100g, respectively), and fat content
      was lower in this sample (12.20+/-1.60g/100g) compared with the other treatments,
      with mean values between 15.72 and 20.50g/100g. Each protein fraction presented a
      different behavior during thermocoagulation. In particular, the recovery of beta
      lactoglobulin and alpha-lactalbumin in the cheese increased as their content
      increased in the mixtures. It was concluded that concentrating ovine rennet whey
      improved the extent of heat-induced protein aggregation during the thermal
      coagulation process. This resulted in a better recovery of each protein fraction
      in the product, and in a consequent increase of ricotta cheese yield. 

PMID- 24856987
TI  - Short communication: prevalence, risk factors, and a field scoring system for
      udder cleft dermatitis in Dutch dairy herds.
AB  - Udder cleft dermatitis (UCD) is a well-known disorder in dairy cows. Veterinary
      literature about this subject, however, is scarce. The objectives of this study
      were to define a clinical scoring system for UCD, estimate the within-herd
      prevalence of UCD, and identify potential risk factors of UCD at cow and herd
      level. On 20 randomly selected dairy farms in the Netherlands, each lactating cow
      was photographed from a ventral, lateral, and caudal position. A scoring system
      with 6 categories of severity of UCD was proposed based on the ventral
      photographs. Cow measures such as udder width and depth, and front quarter
      attachment were determined from the lateral and caudal photographs. A
      questionnaire was conducted on each farm during farm visits. Udder cleft
      dermatitis, defined as a score 3 or higher, was detected in 5.2% of the 948 cows
      involved in this study. Within-herd prevalences of UCD ranged between 0 and 15%
      and UCD was found in 16 (80%) of the participating farms. Cows with a deep udder
      (relative to the hock), large front quarters, and a small angle between udder and
      abdominal wall were more likely to develop UCD. Production level and use of a
      footbath were identified as being positively associated with herd-level UCD
      prevalence. Herd size and average bulk milk somatic cell count did not seem to be
      associated with UCD prevalence. Because of the small herd sample size, no firm
      conclusions were drawn on herd-level risk factors. However, results from this
      study can be used in designing a future longitudinal UCD study. The prevalences
      of UCD found in the present study illustrate the current UCD situation in the
      Netherlands. Our results demonstrate that multiple potential risk factors of UCD
      could be identified at both the cow and herd level. 

PMID- 24856988
TI  - Seasonal variation in the composition and melting behavior of milk fat.
AB  - Dairy bulk tank milk was sampled during 1yr from 2 conventional (C1 and C2) and 1
      organic dairy (O1) for studying the seasonal variation as well as the variation
      between dairies in the composition and properties of milk fat. The composition of
      fatty acids (FA) as well as triglycerides (TAG) in milk fat was analyzed, and the
      melting properties of milk fat were analyzed by use of differential scanning
      calorimetry. The main differences in fat content and composition of FA in milk
      fat between dairies included a higher fat content, greater proportion of C18:0,
      and smaller proportion of C16:0 in milk from dairy C2, which could be associated
      with a higher frequency of Jersey herds supplying milk to this dairy. The organic
      milk was characterized by a higher proportion of C18:3n-3, C18:2 cis-9,trans-11,
      C6 to C14, a lower proportion of C18:1 cis-9, and a higher melting point of the
      low-melting fraction. The TAG composition showed a greater proportion of C24 to
      C38 TAG in milk fat from dairy O1 and a greater proportion of C52 to C54 TAG in
      milk fat from dairy C2, which was in accordance with the differences in FA
      composition. Melting point of the low-melting fraction was higher for milk fat
      from dairy O1 compared with dairies C1 and C2, whereas no differences between
      dairies were observed with respect to melting points of the medium- and high
      melting fractions. The seasonal variation in FA composition was most pronounced
      for dairy O1 although similar patterns were observed for all dairies. During the
      summer, the content of C18:0 and C18:1 cis-9 in milk fat was greater, whereas the
      content of C14:0 and C16:0 was lower. In addition, the content of C18:2 cis
      9,trans-11 and C18:1 trans-11 increased in late summer for dairy O1. The
      differential scanning calorimetry thermograms of individual milk fat samples
      could be divided into 3 groups by principal component analysis. For dairy O1,
      summer samples belonged to group 1, spring and autumn samples to group 2, and
      winter samples to group 3. For dairy C1 winter samples (group 2), were separated
      from other samples (group 1), and for dairy C2 all samples were in group 1.
      Individual melting points were related to FA composition, and the melting point
      of the low-melting fraction was positively correlated to the content of C14:0 and
      C16:0 in milk fat and negatively correlated to the content of C18:1 cis-9 and
      C18:0. 

PMID- 24856989
TI  - Glucocorticoid treatment in rheumatoid arthritis.
AB  - INTRODUCTION: In spite of its broad use since 1950 the role of low-dose
      glucocorticoids (GCs) (up to 7.5 mg/day prednisone) in the treatment of
      rheumatoid arthritis is still controversial. AREAS COVERED: Publications
      comparing disease-modifying anti-rheumatic drugs (DMARD) plus prednisolone with
      DMARD monotherapy were reviewed. Most studies reported greater clinical
      improvement and greater inhibition of damage progression in the prednisone group.
      These advantages had vanished after 6 - 12 months in most studies. EXPERT
      OPINION: Several limitations of the studies are discussed. Often the advantage of
      GC treatment was not clinically important. Long-term data are needed to evaluate
      the real benefit of GC treatment in relation to its toxicity. Knowing the
      potential toxicity 'bridging' GC treatment should be reserved for patients at
      high risk of damage progression; a reliable method to identify these patients is
      needed. The toxicity of low-dose GC treatment is often played down. The reporting
      is incomplete. The increased mortality ratio with GC treatment is rarely
      mentioned. High cumulative doses are a risk factor. A more comprehensive set of
      toxicity items is urgently needed. Problems of GC treatment are the 'drug
      addiction' of the patient and the difficulty to reduce or withdraw prednisone.

PMID- 24856990
TI  - Acute respiratory distress syndrome in the pediatric age: an update on advanced
      treatment.
AB  - Acute respiratory distress syndrome (ARDS) is a heterogeneous syndrome that lacks
      definitive treatment. The cornerstone of management is sound intensive care
      treatment and early anticipatory ventilation support. A mechanical ventilation
      strategy aiming at optimal alveolar recruitment, judicious use of positive end
      respiratory pressure (PEEP) and low tidal volumes (VT) remains the mainstay for
      managing this lung disease. Several treatments have been proposed in rescue
      settings, but confirmation is needed from large controlled clinical trials before
      they be recommended for routine care. Non-invasive ventilation (NIV) is suggested
      with a cautious approach and a strict selection of candidates for treatment. Mild
      and moderate cases can be efficiently treated by NIV, but this is contra
      indicated with severe ARDS. The extra-corporeal carbon dioxide removal (ECCO2 R),
      used as an integrated tool with conventional ventilation, is playing a new role
      in adjusting respiratory acidosis and CO2. The proposed benefits of ECCO2 R over
      extra-corporeal membrane oxygenation (ECMO) consist in a reduction of artificial
      surface contact, avoidance of pump-related side effects and technical
      complications, as well as lower costs. The advantages and disadvantages of
      inhaled nitric oxide (iNO) are better recognized today and iNO is not recommended
      for ARDS and acute lung injury (ALI) in children and adults because iNO results
      in a transient improvement in oxygenation but does not reduce mortality, and may
      be harmful. Several trials have found no clinical benefit from various surfactant
      supplementation methods in adult patients with ARDS. However, studies which are
      still controversial have shown that surfactant supplementation can improve
      oxygenation and decrease mortality in pediatric and adolescent patients in
      specific conditions and, when applied in different modes and doses, also in
      neonatal respiratory distress syndrome (RDS) of preemies. Management of ARDS
      remains supportive, aimed at improving gas exchange and preventing complications.
      Progress in the treatment of ARDS must be addressed toward the new paradigm of
      the disease pathobiology to be applied to the disease definition and to predict
      the treatment outcome, also with the perspective to develop predictive and
      personalized medicine that highlights new and challenging opportunities in terms
      of benefit for patient's safety and doctor's responsibility, with further medico
      legal implication. 

PMID- 24856991
TI  - Patterns and etiology of acute and chronic lung injury: insights from
      experimental evidence.
AB  - Adequate pulmonary function is pivotal for preterm infants. Besides being
      structurally immature, the preterm lung is susceptible to injury resulting from
      different prenatal conditions and postnatal insults. Lung injury might result in
      impaired postnatal lung development, contributing to chronic lung disease of
      prematurity, bronchopulmonary dysplasia (BPD). This review focuses on lung injury
      mediated by and related to inflammatory changes in the lung. We give an overview
      on experimental models which have helped to elucidate mechanisms of pulmonary
      inflammation in prematurity. We describe experimental data linking acute and
      chronic chorioamnionitis with intrapulmonary inflammation, lung maturation and
      surfactant production in various animal models. In addition, experimental data
      has shown that fetal inflammatory response is modulated by the fetus himself.
      Experimental data has therefore helped to understand differential effects on lung
      function and lung maturation exerted by maternal administration of potentially
      anti-inflammatory substances like glucocorticosteroids (GCS). New approaches of
      modulation of pulmonary inflammation/injury caused by postnatal interventions
      during resuscitation and mechanical ventilation have been studied in animal
      models. Postnatal therapeutic interventions with widely used drugs like oxygen,
      steroids, surfactant, caffeine and vitamin A have been experimentally and
      mechanistically assessed regarding their effect on pulmonary inflammation and
      lung injury. Carefully designed experiments will help to elucidate the complex
      interaction between lung injury, lung inflammation, repair and altered lung
      development, and will help to establish a link between lung alterations
      originating in this early period of life and long-term adverse respiratory
      effects. 

PMID- 24856992
TI  - [Clinical application of nasal intermittent positive pressure ventilation in
      initial treatment of neonatal respiratory distress syndrome].
AB  - OBJECTIVE: To study the clinical effectiveness and safety of nasal intermittent
      positive pressure ventilation (NIPPV) in the initial treatment of neonatal
      respiratory distress syndrome (NRDS) and the initial setting of NIPPV parameters.
      METHODS: One hundred neonates with NRDS were divided into NIPPV group (n=50) and
      nasal continuous positive airway pressure (NCPAP) group (n=50). A randomized
      controlled study was conducted to compare the effectiveness of NIPPV versus NCPAP
      in the initial treatment of NRDS from the following aspects: reducing CO2
      retention, improving oxygenation, reducing second endotracheal intubation and
      second use of pulmonary surfactant (PS), reducing the duration of invasive
      respiratory support, reducing the duration of oxygen use, and reducing the
      incidence of air leak, abdominal distension and ventilator-associated pneumonia.
      RESULTS: After 1 and 6 hours of noninvasive respiratory support, the NIPPV group
      was superior to the NCPAP group with respect to the reduction in CO2 retention
      and improvement in oxygenation (P<0.05); in addition, compared with the NCPAP
      group, the NIPPV group had significantly lower rates of second endotracheal
      intubation and second PS use, significantly shorter duration of invasive
      respiratory support and time of FiO2 >0.21, and significantly lower incidence of
      apnea and ventilator-associated pneumonia (P<0.05); there were no significant
      differences in the incidence of air leak and abdominal distention between the two
      groups. CONCLUSIONS: NIPPV is effective and safe in the initial treatment of NRDS
      and holds promise for clinical application.

PMID- 24856993
TI  - [Correlation between end-tidal carbon dioxide and partial pressure of arterial
      carbon dioxide in ventilated newborns].
AB  - OBJECTIVE: To study the correlation between end-tidal carbon dioxide (PetCO2) and
      partial pressure of arterial carbon dioxide (PaCO2) in ventilated newborns.
      METHODS: Thirty-one ventilated newborn underwent mainstream PetCO2 monitoring;
      meanwhile, arterial blood gas analysis was performed. The correlation and
      consistency between PetCO2 and PaCO2 were assessed. RESULTS: A total of 85 end
      tidal and arterial CO2 pairs were obtained from 31 ventilated newborns. The mean
      PetCO2 (41+/-10 mm Hg) was significantly lower than the corresponding mean PaCO2
      (46+/-11 mm Hg) (P<0.01). There was a significant positive correlation between
      PetCO2 and PaCO2 (r=0.92, P<0.01). The overall PetCO2 bias was 5.1+/-4.3 mm Hg
      (95% limits of consistency, -3.3 to 13.6 mmHg), and 5% (4/85) of the points were
      beyond the 95%CI. When the oxygenation index (OI) was less than 300 mm Hg (n=48),
      there was a significant positive correlation between PetCO2 and PaCO2 (r=0.85,
      P<0.01); the PetCO2 bias was 5.9+/-4.3 mm Hg (95% limits of consistency, -2.6 to
      14.5 mm Hg), and 4.2% (2/48) of the points were beyond the 95%CI. When the OI was
      more than 300 mm Hg (n=37), there was also a significant positive correlation
      between PetCO2 and PaCO2 (r=0.91, P<0.01); the PetCO2 bias was 4.1+/-4.1 mm Hg
      (95% limits of consistency, -3.9 to 12.1 mm Hg), and 5% (2/37) of the points were
      beyond the 95%CI. CONCLUSIONS: There is a good correlation and consistency
      between PetCO2 and PaCO2 in ventilated newborns.

PMID- 24856994
TI  - [Association of Ureaplasma urealyticum infection with bronchopulmonary dysplasia
      in very low birth weight infants with respiratory distress syndrome].
AB  - OBJECTIVE: To study the relationship between Ureaplasma urealyticum (UU)
      infection in the lower respiratory tract and the incidence of bronchopulmonary
      dysplasia (BPD) in very low birth weight (VLBW) infants with respiratory distress
      syndrome (RDS). METHODS: Seventy-three VLBW infants diagnosed with neonatal RDS,
      who had received at least one dose of pulmonary surfactant, as well as mechanical
      ventilation, and were hospitalized for over 28 days, were recruited. Endotracheal
      aspirates were obtained from the lower respiratory tract and examined by real
      time PCR to detect UU DNA. The infants were divided into UU infection and non-UU
      infection groups according to examination results. Clinical characteristics and
      the incidence of BPD were compared between the two groups. RESULTS: Compared with
      the non-UU infection group, the UU infection group had a higher rate of maternal
      vaginal delivery, higher incidence of recurrent nosocomial pulmonary infection
      and premature rupture of membranes (PROM), and longer durations of PROM, oxygen
      supplementation, and hospital stay; in addition, the UU infection group had
      higher plasma IgM level, leukocyte count, and neutrophil count within 3 hours
      after birth. Among 73 VLBW infants, 45 developed BPD; the incidence of BPD in the
      UU infection group was 90% (19/21), versus 50% (26/52) in the non-UU infection
      group (P<0.01). CONCLUSIONS: UU infection in the lower respiratory tract
      increases the incidence of BPD in VLBW infants with RDS.

PMID- 24856995
TI  - [Clinical analysis of twin-twin transfusion syndrome complicated by cardiac
      abnormalities in preterm infants].
AB  - OBJECTIVE: To investigate the complications of twin-twin transfusion syndrome
      (TTTS) in preterm infants and to analyze the clinical conditions and prognosis of
      cardiac abnormalities in TTTS recipients. METHODS: A retrospective analysis was
      performed on the clinical data of 17 pairs of preterm infants with TTTS born
      between June 2009 and December 2012. RESULTS: Compared with the recipients, the
      donors had significantly lower body weights (1.4+/-0.6 kg vs 1.9+/-0.6 kg;
      P<0.05). With treatment during pregnancy, cardiac complications were found in 14
      cases, and brain injuries in 12 cases. The proportion of recipients with cardiac
      abnormalities (60%) was higher than that of donors (24%). Among 10 recipients who
      had cardiac complications, cardiac abnormalities mainly included valve
      thickening, stenosis, or atresia (50%). CONCLUSIONS: Among preterm infants with
      TTTS, the recipients are more susceptible to complications of valvular heart
      disease and cardiomyopathy. Fetal echocardiography, evaluation of cardiac
      function, and treatment should be performed for recipients as early as possible
      to improve the prognosis.

PMID- 24856996
TI  - [A contrastive study of corpus callosum area in very preterm and full-term
      infants].
AB  - OBJECTIVE: To compare the differences between full-term and VLBW premature
      infants at term equivalent for the whole and sub-regional corpus callosum areas
      in order to provide reference for monitoring the extrauterine development of
      corpus callosum in VLBW premature infants. METHODS: Brain MR image data of 24
      term infants with a gestational age of 39 weeks were collected within 24 hours
      after birth. Brain MR image of 30 VLBW neonates at 39 weeks' gestational age
      equivalent were successfully obtained. Routine T1WI, T2WI and DWI were applied.
      T1-weighted images on the mid-sagittal slice were selected, analyzed and
      measured. Forty-nine eligible MR images of them were chosen, 21 cases from the
      full-term infant group and 28 cases from the premature infant group. Corpus
      callosum and brain MR images were then sketched by two radiographic doctors. All
      data were analyzed by the Image Processing Function of MATLAB R2010a, and the
      whole corpus callosum and six sub-regions were obtained. RESULTS: The whole
      corpus callosum, anterior mid-body, posterior mid-body, isthmus and splenium area
      in the premature infant group were smaller than those in the full-term infant
      group (P<0.05), but the differences of Genu and rostral body area between the two
      groups was not statistically significant (P>0.05). CONCLUSIONS: The areas of the
      whole corpus callosum, anterior mid-body, posterior mid-body, isthmus and
      splenium in VLBW preterm infants at term are reduced, suggesting that the
      posterior end of the corpus callosum is probably most vulnerable to insults
      following pathogenic factors.

PMID- 24856997
TI  - [Mutations in UGT1A1 gene in neonates with hyperbilirubinemia of Guangxi Heiyi
      Zhuang nationality].
AB  - OBJECTIVE: To study the distribution of mutations of UDP-glucuronosyltransferase
      1A1 (UGT1A1) gene and its relationship with hyperbilirubinemia among neonates
      with hyperbilirubinemia of Guangxi Heiyi Zhuang nationality. METHODS: Total
      genomic DNA was extracted from the blood of 100 neonates with hyperbilirubinemia
      (case group) and 100 neonates without hyperbilirubinemia (control group), all of
      whom were selected from Guangxi Heiyi Zhuang population. TATA box and all exons
      of UGT1A1 gene were amplified by PCR and directly sequenced. RESULTS: (TA)7
      insertion mutation in TATA box, G71R missense mutation in exon 1, and 4 single
      nucleotide polymorphisms (SNPs) (rs199539868, rs114982090, rs1042640 and rs8330)
      in exon 5 were observed. The allele frequency of G71R mutation in the case group
      was significantly higher than that in the control group (P<0.01). There were no
      significant differences in the genotype distribution and allele frequency of TATA
      box mutation and SNPs (rs1042640 and rs8330) between the two groups (P>0.05). The
      logistic regression analysis showed that the odds ratios (95% confidence
      intervals) of UGT1A1 TATA box mutation, G71R mutation, and SNPs (rs1042640 and
      rs8330) associated with the development of neonatal hyperbilirubinemia were 0.846
      (0.440, 1.629), 3.932 (1.745, 8.858), 0.899 (0.364, 2.222), respectively.
      CONCLUSIONS: (TA)7 insertion mutation and G71R missense mutation of UGT1A1 gene
      are common mutation types in neonates with hyperbilirubinemia of Guangxi Heiyi
      Zhuang nationality. Four SNPs (rs199539868, rs114982090, rs1042640, and rs8330)
      was first reported in China. UGT1A1 G71R missense mutation is a risk factor for
      hyperbilirubinemia in neonates of Guangxi Heiyi Zhuang nationality.

PMID- 24856998
TI  - [Clinical characteristics of childhood leukemia with EVI1 gene and BCR/ABL gene
      co-expression].
AB  - OBJECTIVE: To study the clinical characteristics of ecotopic viral integration
      site-1 (EVI1) and BCR/ABL positive childhood leukemia. METHODS: Clinical data of
      four children with EVI1 and BCR/ABL positive leukemia and eight children with
      BCR/ABL positive but EVI1 negative chronic myeloid leukemia (CML) were
      retrospectively analyzed. RESULTS: In the four children with EVI1 and BCR/ABL
      positive leukemia, two were initially diagnosed with chronic phase of CML, one
      with accelerated phase of CML and one with high-risk acute lymphoblastic leukemia
      (ALL). There were no significant differences in clinical characteristics at
      diagnosis between the patients with EVI1 and BCR/ABL positive leukemia and
      BCR/ABL positive but EVI1 negative leukemia. CD33 and CD38 were highly expressed
      and t(9;22) abnormality was present in all patients with EVI1 and BCR/ABL
      positive leukemia. Two of the 3 children with EVI1 and BCR/ABL positive CML
      achieved complete remission one or three months after treatment. Acquired
      negative status conversion occurred for EVI1 but not BCR/ABL in one CML case. The
      3 children with EVI1 and BCR/ABL positive CML survived 20, 13 and 14 months,
      respectively, without recurrence. The child with EVI1 and BCR/ABL positive ALL
      failed to achieve complete remission after the first course of treatment and
      discontinued further treatment. CONCLUSIONS: Co-expression of EVI1 and BCR/ABL
      fusion gene can be found in childhood CML and ALL. The relatively rare leukemia
      has not significant difference respect to clinical characteristics. Prognosis of
      the disease needs to be determined by clinical studies with a larger sample size.

PMID- 24856999
TI  - [A comparison of minimal residual disease in children with acute lymphoblastic
      leukemia of different genetic abnormalities].
AB  - OBJECTIVE: To study the changes of minimal residual disease (MRD) in children
      with B cell acute lymphoblastic leukemia (B-ALL) of different genetic
      abnormalities. METHODS: Between February 2004 and April 2013, 271 newly diagnosed
      B-ALL pediatric patients who had finished the induction chemotherapy were
      enrolled in the study. The characteristics of changes in MRD in patients with
      different genetic abnormalities on the 15th day and at the end of the induction
      therapy were analyzed. RESULTS: On the 15th day of the induction chemotherapy,
      the MRD positive proportion in patients with hyperdiploid was higher on all the
      three cut-off levels of MRD>=0.1%, 1% and 10% compared to patients without
      hyperdiploid (P<0.05), but there was no significant difference in the MRD
      positive proportion on the three levels of MRD between the TEL-AML1-positive and
      TEL-AML1-negative groups (P>0.05). On the end of induction chemotherapy, there
      was no significant difference in the MRD positive proportion on the three levels
      of MRD between the patients with and without hyperdiploid (P>0.05), neither
      between the BCR-ABL-positive and negative groups. The MRD positive proportion in
      TEL-AML1-negative patients was significantly higher than in TEL-AML1-positive
      patients on all three levels of MRD (P<0.05). The MRD positive proportion on two
      levels of MRD>=0.01% and 0.1% in E2A-PBX1-negative patients was significantly
      higher than in E2A-PBX1-positive patients (P<0.05). CONCLUSIONS: Children with B
      ALL of different genetic abnormalities have different MRD levels during, and at
      the end of, induction therapy. The prognostic significance of MRD may be related
      to the genetic abnormalities.

PMID- 24857000
TI  - [Correlations between 6-mercaptopurine treatment-related adverse reactions in
      children with acute lymphoblastic leukemia and polymorphisms of thiopurine
      methyltransferase gene].
AB  - OBJECTIVE: To explore 6-mercaptopurine (6-MP) treatment-related adverse reactions
      in children with acute lymphoblastic leukemia (ALL), and to assess the
      association between the polymorphisms of thiopurine methyltransferase (TPMT) gene
      and these 6-MP related toxicities. METHODS: Total RNA was extracted from bone
      marrow samples of 46 children with ALL and was then reversed to cDNA. TPMT(*)1S
      and (*)3C were screened by denaturing gradient gel electrophoresis (DGGE)
      combining with DNA sequencing. Drug toxicities were classified according to
      national cancer institute-common toxicity criteria version 3.0 (NCI CTC 3.0). The
      relationship between TPMT gene polymorphisms and the adverse reactions of 6-MP
      treatment was analyzed. RESULTS: During the maintenance treatment period, 22%
      (10/46) of children discontinued 6-MP treatment because of serious adverse
      reactions. Two children with TPMT(*)3C genotypes presented severe adverse
      reactions, including 1 child with homozygotic mutation who had 6-MP dose-related
      myelosuppression and hepatotoxicity. The main side effects of 6-MP were
      myelosuppression, hepatotoxicity and gastrointestinal reaction. And there were no
      significant differences between TPMT(*)1S genotypes and severe myelosuppression
      or hepatotoxicity caused by 6-MP (P>0.05). CONCLUSIONS: TPMT(*)3C may correlate
      with severe adverse reactions caused by 6-MP.

PMID- 24857001
TI  - [Prognostic significance of coagulation disorders in children with hemophagocytic
      syndrome].
AB  - OBJECTIVE: To study the prognostic significance of coagulation disorders in
      children with hemophagocytic syndrome (HPS). METHODS: Thirty-five children with
      HPS were retrospectively studied to analyze the etiology, clinical
      characteristics, laboratory results and treatment outcomes. RESULTS: After
      treatment, 27 of the 35 HPS patients survived, and the other 8 cases died. All
      cases were treated according to the HLH-2004 protocol, but etoposide (VP-16) was
      not used in 10 of them. The response rate in patients who received VP-16 (22/25,
      88%) was significantly higher than that in those not receiving VP-16 (5/10, 50%)
      (P<0.05). Compared with the survival group, the dead group had significantly
      lower platelet count, fibrinogen level, and VP-16 utilization rate (P<0.05) but
      significantly longer activated partial thromboplastin time and prothrombin time
      (P<0.05). CONCLUSIONS: Coagulation function can be used as an indicator of
      disease outcome. It is essential for improving the clinical outcome of HPS to
      monitor the coagulation function during treatment, detect and correct
      abnormalities in time, and provide treatment strictly according to the HLH-2004
      protocol.

PMID- 24857002
TI  - [Influence of OM-85 BV on hBD-1 and immunoglobulin in children with asthma and
      recurrent respiratory tract infection].
AB  - OBJECTIVE: To observe the clinical therapeutic effect of OM-85 BV(OM-85 Broncho
      Vaxom) in children with asthma and recurrent respiratory tract infection, and the
      effect of OM-85 BV on human beta-defensins 1 (hBD-1) and immunoglobulin levels.
      METHODS: Sixty-two children with asthma and recurrent respiratory infection
      treated between 2011 January and December were divided into two groups by the
      randomized, double blind method: a treatment group and a control group. With
      inhaling corticosteroids, the treatment group was given OM-85 BV, and the control
      group was given a placebo. Clinical curative effects and adverse reactions were
      observed. Serum levels of hBD-1, IgA, IgG, IgM and urea and alanine
      aminotransferase (ALT) were measured before treatment and 6 months and 12 months
      after treatment. RESULTS: Compared with the control group and before treatment,
      the frequency of respiratory tract infection was reduced in the treatment group 6
      months and 12 months after treatment (P<0.05), and serum levels of hBD-1, IgA and
      IgG in the treatment group increased significantly (P<0.05). There was no
      significant difference in serum levels of urea, ALT and IgM between the control
      and treatment groups (P>0.05). Mild adverse reactions occurred in 3 cases in the
      two groups, 2 cases of abdominal pain and 1 cases of constipation. CONCLUSIONS:
      OM-85 BV can improve serum levels of hBD-1, IgA and IgG, reduce the occurrence of
      acute respiratory tract infection and cause mild adverse reactions, suggesting
      its satisfactory therapeutic effect and safety in the treatment of asthma
      combined with recurrent respiratory tract infection in children.

PMID- 24857003
TI  - [Therapeutic effect of ketogenic diet for refractory epilepsy in children: a
      prospective observational study].
AB  - OBJECTIVE: To study the clinical efficiency, electroencephalogram (EEG) changes
      and cognitive improvements of ketogenic diet (KD) in children with refractory
      epilepsy. METHODS: Twenty pediatric patients (7-61 months in age) with refractory
      epilepsy were recruited between August 2012 and August 2013. KD therapy was
      performed on all participants for at least 3 months based on a fasting initiation
      protocol with the lipid-to-nonlipid ratio being gradually increased to 4 : 1.
      Seizure frequency, type and degree were recorded before and during KD therapy. A
      24 hours video-electroencephalogram (V-EEG) examination and Gesell Developmental
      Scale assessment were performed prior to KD therapy, and 3, 6, 9 months after KD
      therapy. RESULTS: Six patients became seizure free after KD therapy, with a
      complete control rate of 30%. Seizure frequency reduction occurred in 13 (65%)
      patients, EEG improvement in 8 (40%) patients, and improvement in Gesell
      Developmental Scales (gross motor and adaptability in particular) in 6 (30%)
      patients. The KD therapy-related side effects were mild. CONCLUSIONS: KD therapy
      is safety and effective in reducing seizure frequency and improving EEG and
      cognitive function in children with refractory epilepsy.

PMID- 24857004
TI  - [Three PHEX gene mutations in Chinese subjects with hypophosphatemic rickets and
      literature review].
AB  - The clinical data of three Chinese children who had been definitely diagnosed
      with X-link dominate hypophosphatemic rickets (XLH) by gene mutation analysis of
      phosphate-regulating gene with homologies to endopeptidases on the X chromosome
      (PHEX) were retrospectively studied and the relevant literature was reviewed.
      PHEX gene mutations were detected in all 3 XLH children; a nonsense mutation
      (c.58C>T) in one case and splicing mutations (c.1645+1G>A, c.436+1G>A) in the
      other two cases. Among these mutations, c.436+1G>A was novel. As of January 2014,
      a total of 329 PHEX gene mutations were reported, primarily within three mutation
      hot spots, throughout the world. Missense mutations accounted for the highest
      proportion (24%) among all mutations. There is literature showing geographic
      differences in the total number of XLH subjects and PHEX mutation types across
      the world. In the current literature, 89 cases of XLH with 28 types of PHEX
      mutations have been reported in the population of mainland China. Exon 22 is the
      most frequent mutation site (18%) and missense mutations are the most common type
      of mutations (61%). It is concluded that exon 22 is the mutation hot spot and
      missense mutation is the most common type of mutation in the PHEX gene in Chinese
      XLH patients and that c.436+1G>A detected in this study is a novel PHEX gene
      mutation in Chinese with XLH. 

PMID- 24857005
TI  - [Risk factors for unintentional injury among children in rural areas of Liling,
      Hunan Province, China].
AB  - OBJECTIVE: To evaluate the risk factors for unintentional injury among children
      in the rural areas of Liling, Hunan Province, China, as a basis for developing
      prevention and intervention measures for unintentional injury in rural children.
      METHODS: A total of 3 257 students, aged between 5 and 16 years from 4 middle
      schools and 2 primary schools in eastern and western rural areas of Liling were
      recruited in October 2013 by stratified sampling and cluster sampling. The
      general personal information and data on family backgrounds, living environment,
      and incidence of unintentional injury were collected from all subjects through a
      self-designed questionnaire. The risk factors for childhood unintentional injury
      were assessed by an unconditional multiple logistic regression analysis. RESULTS:
      Out of the 3 257 subjects, 356 (10.93%) were injured during the 12-month period
      prior to the study. The univariate analysis showed that unintentional injury in
      these subjects was related to sex, left-behind status, times of internet surfing
      in internet bars per week, parent companion or not, age of guardian, degree of
      harmony of parents' marital relationship, employment status of one or both
      parents as a migrant worker, storage of fireworks and firecrackers at home or
      not, violence in residential areas, and participation or not in violence in
      residential areas. The unconditional multiple logistic regression analysis showed
      that the major risk factors for unintentional injury in these subjects were male
      gender (OR=0.751, P=0.013), left-behind status (OR=1.779, P<0.001), storage of
      fireworks and firecrackers at home (OR=1.337, P=0.028) and violence around
      residential areas (OR=1.517, P<0.001). CONCLUSIONS: Risk for unintentional injury
      is multifactorial among children in the rural areas of Liling, Hunan. To reduce
      the incidence of unintentional injury in children in Liling, particular attention
      should be paid to boys, left-behind children, children who have home storage of
      fireworks and firecrackers and children who are living in areas with frequent
      violence.

PMID- 24857006
TI  - [Effects of recombinant human interleukin-11 on LPS-induced intestinal epithelial
      cell injury in rats].
AB  - OBJECTIVE: To study the effects of recombinant human interleukin-11 (rhIL-11) on
      the proliferation and apoptosis of rat intestinal epithelial cell line (IEC-6).
      METHODS: IEC-6 cells were treated with LPS to establish necrotizing enterocolitis
      (NEC) model in vitro. rhIL-11 (100 ng/mL) was administered following LPS
      treatment and these cells were used as the IL-11 treatment group. The cells
      treated with normal saline only served as the control group. MTT assay was used
      to determine an optimal concentration (5-200 MUg/mL) and time (1-24 h). MTT assay
      was used to measure the proliferation of IEC-6 cells at 3, 6, 9 and 12 hours
      after rhIL-11 treatment. Flow cytometry was used to evaluate the apoptosis of IEC
      6 cells. RESULTS: IEC-6 cells treated with various concentrations of LPS at
      various time points showed a lower proliferation than the control group (P<0.05).
      After 9 hours of rhIL-11 treatment, the proliferation activity of IEC-6 cells in
      the IL-11 treatment group significantly increased compared with the NEC model
      group without rhIL-11 treatment (P<0.05), reaching to the level of the control
      group. The total apoptotic and necrotic rate of IEC-6 cells in the IL-11
      treatment group decreased significantly compared with the NEC model group without
      rhIL-11 treatment (P<0.01), but were still higher than the control group
      (P<0.05). CONCLUSIONS: rhIL-11 can promote proliferation and reduce apoptotic and
      necrotic rates of IEC-6 cells treated with LPS.

PMID- 24857007
TI  - [Cyanidin-3-glucoside attenuates body weight gain, serum lipid concentrations and
      insulin resistance in high-fat diet-induced obese rats].
AB  - OBJECTIVE: Cyanidin-3-glucoside (C3G) is the main active ingredient of
      anthocyanidin. This study aimed to evaluate the effects of C3G on body weight
      gain, visceral adiposity, lipid profiles and insulin resistance in high-fat diet
      induced obese rats. METHODS: Thirty male Sprague-Dawley rats were randomly
      divided into a control group (n=8) and a high fat diet group (n=22), and were fed
      with standard diet or high fat diet. Five weeks later, 17 high-fat diet-induced
      obese rats were randomly given C3G [100 mg/(kg.d)] or normal saline via
      intragastric administration for 5 weeks. Five weeks later, body weight, visceral
      adiposity and food intake were measured. Blood samples were collected for
      detecting fasting glucose, serum insulin, lipid profiles and adiponectin. Insulin
      resistance index, atherosclerosis index and average feed efficiency ratio were
      calculated. RESULTS: C3G supplementation markedly decreased body weight, visceral
      adiposity, average feed efficiency ratio, triglyceride, total cholesterol, low
      density lipoprotein cholesterol, fasting glucose, serum insulin, insulin
      resistance index and atherosclerosis index in high-fat diet-induced obese rats.
      C3G supplementation normalized serum adiponectin and high density lipoprotein
      cholesterol levels in high-fat diet-induced obese rats. CONCLUSIONS: Cyanidin-3
      glucoside can reduce body weight gain, and attenuate obesity-associated
      dyslipidemia and insulin resistance in high-fat diet-fed rats via up-regulating
      serum adiponectin level.

PMID- 24857008
TI  - [Epidemiological characteristics of hand-foot-mouth disease in 210 children].

PMID- 24857009
TI  - [Partial DiGeorge syndrome caused by 22q11.2 typical microdeletion without
      cardiac defect: report of two cases].

PMID- 24857010
TI  - [Diagnosis of tuberous sclerosis complex by gene sequencing in an infant].

PMID- 24857011
TI  - [Pasteurella haemolytica septicemia in a child].

PMID- 24857012
TI  - [Pathogenesis of human metapneumovirus infection and research on attenuated live
      vaccine].
AB  - Numerous studies have indicated that human metapneumovirus (hMPV) is an important
      viral pathogen in acute respiratory infections in children, presenting similar
      manifestations with respiratory syncytial virus (RSV). HMPV infection peaks in
      the winter-spring season and is more prevalent in younger ages, especially in
      children less than 1 year old. Host innate immune response has been implicated in
      recognition of pathogen-associated molecular patterns (PAMPs) of the virus. This
      recognition occurs through host pattern recognition receptors (PRRs). Toll like
      receptors (TLRs) are one of the largest class of PRRs which initiate and regulate
      adaptive immune responses. Some studies have indicated that TLR 3 and TLR 4 may
      play critical roles in hMPV infection. Construction of recombinant mutant viruses
      lacking one or two N-linked glycosylation sites in the F protein by using site
      directed mutagenesis and reverse genetics may be helpful for developing
      attenuated live vaccines. 

PMID- 24857013
TI  - [Effects of central precocious puberty on physical and sexual development in
      children].
AB  - As abnormal pubertal development, central precocious puberty (CPP) is manifested
      by the secondary sexual characteristics, skeletal maturation, and physical
      development in advance. It ultimately affects the adult height of children, even
      producing some psychological and behavioral problems such as fear and anxiety.
      Currently, gonadotropin releasing hormone analogue (GnRHa) is recognized as the
      best medicine worldwide for treating CPP in order to increase children's final
      adult height; however, it has some adverse effects on the growth and development
      of children. This paper reviews the effects of CPP and GnRHa on children's
      physical and sexual development, with the aim of increasing physicians awareness
      of this disease and the safety of medication. 

PMID- 24857014
TI  - [Research advance in autistic traits in non-affected population of autism
      spectrum disorder].
AB  - Autistic traits including social reciprocal deficits, communication deficits and
      stereotyped behaviors, are manifested not only in patients with autism spectrum
      disorders (ASD) and their families, but also in general population. In recent
      years, there has much research related to autistic traits. This article
      summarizes research advance of autistic traits in ASD relations and general
      population.

PMID- 24857015
TI  - The immune space: a concept and template for rationalizing vaccine development.
AB  - Empirical testing of candidate vaccines has led to the successful development of
      a number of lifesaving vaccines. The advent of new tools to manipulate antigens
      and new methods and vectors for vaccine delivery has led to a veritable explosion
      of potential vaccine designs. As a result, selection of candidate vaccines
      suitable for large-scale efficacy testing has become more challenging. This is
      especially true for diseases such as dengue, HIV, and tuberculosis where there is
      no validated animal model or correlate of immune protection. Establishing
      guidelines for the selection of vaccine candidates for advanced testing has
      become a necessity. A number of factors could be considered in making these
      decisions, including, for example, safety in animal and human studies, immune
      profile, protection in animal studies, production processes with product quality
      and stability, availability of resources, and estimated cost of goods. The
      "immune space template" proposed here provides a standardized approach by which
      the quality, level, and durability of immune responses elicited in early human
      trials by a candidate vaccine can be described. The immune response profile will
      demonstrate if and how the candidate is unique relative to other candidates,
      especially those that have preceded it into efficacy testing and, thus, what new
      information concerning potential immune correlates could be learned from an
      efficacy trial. A thorough characterization of immune responses should also
      provide insight into a developer's rationale for the vaccine's proposed mechanism
      of action. HIV vaccine researchers plan to include this general approach in up
      selecting candidates for the next large efficacy trial. This "immune space"
      approach may also be applicable to other vaccine development endeavors where
      correlates of vaccine-induced immune protection remain unknown.

PMID- 24857016
TI  - The testis through the ages.

PMID- 24857017
TI  - [Toxicological analysis is mandatory to interpret elevation in blood lactate
      concentration in toxic alcohol poisoning].

PMID- 24857018
TI  - The choice of anaesthetic--sevoflurane or propofol--and outcome from cancer
      surgery: a retrospective analysis.
AB  - BACKGROUND: Commonly used inhalational hypnotics, such as sevoflurane, are pro
      inflammatory, whereas the intravenously administered hypnotic agent propofol is
      anti-inflammatory and anti-oxidative. A few clinical studies have indicated
      similar effects in patients. We examined the possible association between patient
      survival after radical cancer surgery and the use of sevoflurane or propofol
      anaesthesia. PATIENTS AND METHODS: Demographic, anaesthetic, and surgical data
      from 2,838 patients registered for surgery for breast, colon, or rectal cancers
      were included in a database. This was record-linked to regional clinical quality
      registers. Cumulative 1- and 5-year overall survival rates were assessed using
      the Kaplan-Meier method, and estimates were compared between patients given
      propofol (n = 903) or sevoflurane (n = 1,935). In a second step, Cox proportional
      hazard models were calculated to assess the risk of death adjusted for potential
      effect modifiers and confounders. RESULTS: Differences in overall 1- and 5-year
      survival rates for all three sites combined were 4.7% (p = 0.004) and 5.6% (p <
      0.001), respectively, in favour of propofol. The 1-year survival for patients
      operated for colon cancer was almost 10% higher after propofol anaesthesia.
      However, after adjustment for several confounders, the observed differences were
      not statistically significant. CONCLUSION: Propofol anaesthesia might be better
      in surgery for some cancer types, but the retrospective design of this study,
      with uneven distributions of several confounders, distorted the picture. These
      uncertainties emphasize the need for a randomized controlled trial.

PMID- 24857020
TI  - Distinct tau prion strains propagate in cells and mice and define different
      tauopathies.
AB  - Prion-like propagation of tau aggregation might underlie the stereotyped
      progression of neurodegenerative tauopathies. True prions stably maintain unique
      conformations ("strains") in vivo that link structure to patterns of pathology.
      We now find that tau meets this criterion. Stably expressed tau repeat domain
      indefinitely propagates distinct amyloid conformations in a clonal fashion in
      culture. Reintroduction of tau from these lines into naive cells reestablishes
      identical clones. We produced two strains in vitro that induce distinct
      pathologies in vivo as determined by successive inoculations into three
      generations of transgenic mice. Immunopurified tau from these mice recreates the
      original strains in culture. We used the cell system to isolate tau strains from
      29 patients with 5 different tauopathies, finding that different diseases are
      associated with different sets of strains. Tau thus demonstrates essential
      characteristics of a prion. This might explain the phenotypic diversity of
      tauopathies and could enable more effective diagnosis and therapy.

PMID- 24857022
TI  - The bottleneck of evidence-based fracture care.

PMID- 24857021
TI  - Separate GABA afferents to dopamine neurons mediate acute action of opioids,
      development of tolerance, and expression of withdrawal.
AB  - GABA release from interneurons in VTA, projections from the nucleus accumbens
      (NAc), and rostromedial tegmental nucleus (RMTg) was selectively activated in rat
      brain slices. The inhibition induced by MU-opioid agonists was pathway dependent.
      Morphine induced a 46% inhibition of IPSCs evoked from the RMTg, 18% from NAc,
      and IPSCs evoked from VTA interneurons were almost insensitive (11% inhibition).
      In vivo morphine treatment resulted in tolerance to the inhibition of RMTg, but
      not local interneurons or NAc, inputs. One common sign of opioid withdrawal is an
      increase in adenosine-dependent inhibition. IPSCs evoked from the NAc were
      potently inhibited by activation of presynaptic adenosine receptors, whereas
      IPSCs evoked from RMTg were not changed. Blockade of adenosine receptors
      selectively increased IPSCs evoked from the NAc during morphine withdrawal. Thus,
      the acute action of opioids, the development of tolerance, and the expression of
      withdrawal are mediated by separate GABA afferents to dopamine neurons.

PMID- 24857023
TI  - Imaging techniques for the assessment of fracture repair.
AB  - Imaging of a healing fracture provides a non-invasive and often instructive
      reproduction of the fracture repair progress and the healing status of bone.
      However, the interpretation of this reproduction is often qualitative and
      provides only an indirect and surrogate measure of the mechanical stability of
      the healing fracture. Refinements of the available imaging techniques have been
      suggested to more accurately determine the healing status of bone. Plain
      radiographs provide the ability to determine the degree of bridging of the
      fracture gap and to quantify the amount of periosteal callus formation.
      Absorptiometric measures including dual X-ray absorptiometry and computed
      tomography provide quantitative information on the amount and the density of
      newly formed bone around the site of the fracture. To include the effect of
      spatial distribution of newly formed bone, finite element models of healing
      fracture can be employed to estimate its load bearing capacity. Ultrasound
      technology not only avoids radiation doses to the patients but also provides the
      ability to additionally measure vascularity in the surrounding soft tissue of the
      fracture and in the fracture itself.

PMID- 24857024
TI  - Computational techniques for the assessment of fracture repair.
AB  - The combination of high-resolution three-dimensional medical imaging, increased
      computing power, and modern computational methods provide unprecedented
      capabilities for assessing the repair and healing of fractured bone. Fracture
      healing is a natural process that restores the mechanical integrity of bone and
      is greatly influenced by the prevailing mechanical environment. Mechanobiological
      theories have been proposed to provide greater insight into the relationships
      between mechanics (stress and strain) and biology. Computational approaches for
      modelling these relationships have evolved from simple tools to analyze fracture
      healing at a single point in time to current models that capture complex
      biological events such as angiogenesis, stochasticity in cellular activities, and
      cell-phenotype specific activities. The predictive capacity of these models has
      been established using corroborating physical experiments. For clinical
      application, mechanobiological models accounting for patient-to-patient
      variability hold the potential to predict fracture healing and thereby help
      clinicians to customize treatment. Advanced imaging tools permit patient-specific
      geometries to be used in such models. Refining the models to study the strain
      fields within a fracture gap and adapting the models for case-specific simulation
      may provide more accurate examination of the relationship between strain and
      fracture healing in actual patients. Medical imaging systems have significantly
      advanced the capability for less invasive visualization of injured
      musculoskeletal tissues, but all too often the consideration of these rich
      datasets has stopped at the level of subjective observation. Computational image
      analysis methods have not yet been applied to study fracture healing, but two
      comparable challenges which have been addressed in this general area are the
      evaluation of fracture severity and of fracture-associated soft tissue injury. CT
      based methodologies developed to assess and quantify these factors are described
      and results presented to show the potential of these analysis methods. 

PMID- 24857025
TI  - Delayed union and nonunions: epidemiology, clinical issues, and financial
      aspects.
AB  - Fracture healing is a critically important clinical event for fracture patients
      and for clinicians who take care of them. The clinical evaluation of fracture
      healing is based on both radiographic findings and clinical findings. Risk
      factors for delayed union and nonunion include patient dependent factors such as
      advanced age, medical comorbidities, smoking, non-steroidal anti-inflammatory
      use, various genetic disorders, metabolic disease and nutritional deficiency.
      Patient independent factors include fracture pattern, location, and displacement,
      severity of soft tissue injury, degree of bone loss, quality of surgical
      treatment and presence of infection. Established nonunions can be characterised
      in terms of biologic capacity, deformity, presence or absence of infection, and
      host status. Hypertrophic, oligotrophic and atrophic radiographic appearances
      allow the clinician to make inferences about the degree of fracture stability and
      the biologic viability of the fracture fragments while developing a treatment
      plan. Non-unions are difficult to treat and have a high financial impact.
      Indirect costs, such as productivity losses, are the key driver for the overall
      costs in fracture and non-union patients. Therefore, all strategies that help to
      reduce healing time with faster resumption of work and activities not only
      improve medical outcome for the patient, they also help reduce the financial
      burden in fracture and non-union patients. 

PMID- 24857026
TI  - Biomechanical methods for the assessment of fracture repair.
AB  - The progress of fracture healing is directly related to an increasing stiffness
      and strength of the healing fracture. Similarly the weight bearing capacity of a
      bone directly relates to the mechanical stability of the fracture. Therefore,
      assessing the progress of fracture repair can be based on the measurement of the
      mechanical stability of the healing fracture. However, fracture stability is
      difficult to assess directly due to various obstacles of which shielding of the
      mechanical properties by the fracture fixation construct is the most relevant
      one. Several assessment methods have been proposed to overcome these obstacles
      and to obtain some sort of mechanical surrogate describing the stability of the
      fracture. The most direct method is the measurement of the flexibility of a
      fracture under a given external load, which comprises the challenge of accurately
      measuring the deformation of the bone. Alternative approaches include the
      measurement of load share between implant and bone by internal or by external
      sensors. A direct 3 dimensional measurement of bone displacement is provided by
      radiostereometric analysis which can assess fracture migration and can detect
      fracture movement under load. More indirect mechanical methods induce cyclic
      perturbations within the bone and measure the response as a function of healing
      time. At lower frequencies the perturbations are induced in the form of vibration
      and at higher frequencies in the form of ultrasonic waves. Both methods provide
      surrogates for the mechanical properties at the fracture site. Although
      biomechanical properties of a healing fracture provide a direct and clinically
      relevant measure for fracture healing, their application will in the near future
      be limited to clinical studies or research settings. 

PMID- 24857027
TI  - Gait and function as tools for the assessment of fracture repair - the role of
      movement analysis for the assessment of fracture healing.
AB  - Assessment of gait and function might be as sensitive tool to monitor the
      progress of fracture healing. Currently available assessment tools for function
      use instrumented three dimensional gait analysis or pedobarography. The analysis
      is focused on gait or movement parameters and seeks to identify abnormalities or
      asymmetries between legs or arms. The additional inclusion of muscle function by
      electromyography can further elucidate functional performance and its temporal
      development. Alternative approaches abstain from directly assessing function in
      the laboratory but rather determine the amount of activities of daily living or
      the mere ability to perform defined tasks such as walking, stair climbing or
      running. Some of these methods have been applied to determine recovery after
      orthopaedic interventions including fracture repair. The combination of lab-based
      functional measurements and assessment of physical activities in daily live may
      offer a valuable level of information about the gait quality and quantity of
      individual patients which sheds light on functional limitations or rehabilitation
      of gait and mobility after a disease or injury and the respective conservative,
      medical or surgical treatment. 

PMID- 24857028
TI  - Patient-important outcome for the assessment of fracture repair.
AB  - Current evidence indicates that fracture healing assessment is limited to the use
      of one or two domains (such as pain, range of motion or mobility) in any single
      study. Functional outcome measures, which include physician-rated or observer
      based impairment ratings and patient self-reported or observer-based activity
      limitation measures, better position the effectiveness of a given intervention
      towards patient-important outcomes. Health status measures, for example, cover a
      wide-range of physical, emotional, and social health dimensions. In this paper,
      we will examine the utility of metrics to assess fracture healing that are
      important to both the patient and provider, with selected examples from the
      recent literature. We recommend outcome measures with established and verified
      reliability and validity. Policy-makers and other stakeholders need to have an
      accurate assessment of treatment outcome that includes changes in function over
      time-adequate measures, should be re-applied at periodic intervals. 

PMID- 24857029
TI  - Can we enhance fracture vascularity: What is the evidence?
AB  - Angiogenesis is a vital component of bone healing. The formation of the new blood
      vessels at the fracture site restores the hypoxia and nutrient deprivation found
      at the early stages after fracture whilst at a later stage facilitates
      osteogenesis by the activity of the osteoprogenitor cells. Emerging evidence
      suggests that there are certain molecules and gene therapies that could promote
      new blood vessel formation and as a consequence enhance the local bone healing
      response. This article summarizes the current in vivo evidence on therapeutic
      approaches aiming at the augmentation of the angiogenic signalling during bone
      repair. 

PMID- 24857030
TI  - Biological perspectives of delayed fracture healing.
AB  - Fracture healing is a complex biological process that requires interaction among
      a series of different cell types. Maintaining the appropriate temporal
      progression and spatial pattern is essential to achieve robust healing. We can
      temporally assess the biological phases via gene expression, protein analysis,
      histologically, or non-invasively using biomarkers as well as imaging techniques.
      However, determining what leads to normal versus abnormal healing is more
      challenging. Since the ultimate outcome of fracture healing is to restore the
      original functions of bone, assessment of fracture healing should include not
      only monitoring the restoration of structure and mechanical function, but also an
      evaluation of the restoration of normal bone biology. Currently few non-invasive
      measures of biological factors of healing exist; however, recent studies that
      have correlated non-invasive measures with fracture healing outcome in humans
      have shown that serum TGFbeta1 levels appear to be an indicator of healing versus
      non-healing. In the future, developing additional measures to assess biological
      healing will improve the reliability and permit us to assess stages of fracture
      healing. Additionally, new functional imaging technologies could prove useful for
      better understanding both normal fracture healing and predicting dysfunctional
      healing in human patients. 

PMID- 24857031
TI  - Synergistic effect of natural compounds on the fatty acid-induced autophagy of
      activated hepatic stellate cells.
AB  - Autophagy, a lysosomal pathway to maintain cellular homeostasis, is mediated via
      the mammalian target of rapamycin (mTOR)-dependent pathways. Hepatic stellate
      cells (HSCs), previously termed fat- or vitamin A-storing cells, can
      transdifferentiate into myofibroblast-like cells and are the most relevant cell
      type for overproduction of extracellular matrix (ECM) and development of liver
      fibrosis during injury. However, the role of autophagy in fat metabolism of HSCs
      remains unclear. This study investigates the regulatory effect of natural
      compounds on fatty acid-induced autophagy pathways of nonchemical-induced HSC
      (NHSC) and thioacetamide-induced HSC. Oleic acid (OA) and palmitic acid (PA) have
      shown a significant effect on cell proliferation with oil red O staining and
      Western blot confirming that OA and PA induce fat storage ability and autophagy
      protein expression in NHSC. Natural compounds rutin, curcumin, antroquinonol and
      benzyl cinnamate treatment have shown no effect on the autophagy protein
      expression. Nevertheless, cells pretreated with OA and PA then treated with
      rutin, curcumin, antroquinonol and benzyl cinnamate could significantly induce
      the light chain I/II (LC3 I/II) protein expression. In mTOR-dependent pathway,
      the PI3K-Class I, Akt, and p-mTOR proteins were decreased with PA treatment.
      However, there were no significant changes in PI3K-Class III and Beclin-1 protein
      expressions found to imply that this autophagy is unrelated to the mTOR
      independent pathway. Taken together, the present study unveils rutin and curcumin
      as a possible effective stimulation for fatty acid-induced autophagy via mTOR
      dependent pathways in NHSC. We further suggest the benefits of these natural
      compounds for alleviating liver fibrosis.

PMID- 24857032
TI  - Ionic liquid-based matrix solid-phase dispersion coupled with homogeneous liquid
      liquid microextraction of synthetic dyes in condiments.
AB  - The ionic liquid-based matrix solid-phase dispersion homogeneous liquid-liquid
      microextraction (IL-based MSPD-HLLME) was developed and applied to the extraction
      of four banned dyes, including chrysoidin, safranine O, auramine O and rhodamine
      B, in condiment samples. High performance liquid chromatography was applied to
      the separation and determination of the analytes. The solid sample was directly
      treated by MSPD using ionic liquid as dispersant and the eluate obtained in MSPD
      was treated by HLLME. Some experimental parameters, including type of dispersant,
      ratio of sample to dispersant, type and volume of ionic liquid, type and volume
      of elution solvent, pH value and ionic strength of the elution solvent, amount of
      ion-pairing agent (NH4PF6) and extraction time, were investigated and optimized.
      The linearities for determining the analytes were in the range of 60-2000MUgkg(
      1) for chrysoidin, 40-2000MUgkg(-1) for safranine O and 20-1000MUgkg(-1) for
      auramine O and rhodamine B, with the correlation coefficients ranging from 0.9964
      to 0.9991. The limits of detection for the analytes were between 6.7 and
      26.8MUgkg(-1) and the limits of quantification were between 15.99 and 58.48MUgkg(
      1). When the present method was applied to the analysis of spiked condiment
      samples, the recoveries of the analytes ranged from 90.69 to 113.52% and relative
      standard deviations were lower than 8.2%. The present method combined the
      advantages of MSPD and HLLME, and could be applied for the determination of
      synthetic dyes in condiment samples. 

PMID- 24857033
TI  - Ligand-receptor binding increments in enantioselective liquid chromatography.
AB  - A set of N-derivatized amino acids were separated into enantiomers on a tert
      butylcarbamoylated quinine-based chiral stationary phase (CSP). Quantitative
      structure-property relationship (QSPR) studies were then employed to investigate
      the retention behavior and factors responsible for enantioselectivity.
      Computations were performed using a general linear model and a Free-Wilson matrix
      with indicator variables as structural descriptors. The approach allowed
      calculations of retention increments for first and second eluted enantiomers as
      well as group contributions to enantioselectivity. The results demonstrated that
      the additivity principle of group contributions was obeyed for the majority of
      solutes in the data set. Only a few basic amino acids (Arg, His) needed to be
      removed as they did not fit to such a linear model leading to outliers. The model
      was carefully validated and then utilized to investigate retention and
      enantioselectivity contributions of different protection groups and individual
      amino acid residues. It turned out that primarily protection groups were driving
      retention and enantioselectivity. In contrast, the contribution of amino acid
      residues to enantioselectivity was only significant for secondary amino acids,
      alpha-methylated amino acids, aspartic acid and a few sterically bulky aliphatic
      amino acid residues (Tle, Ile, allo-Ile). Amongst them only the latter group
      contributed positively to enantioselectivity while the other residues mentioned
      reduced enantioselectivity significantly. This type of QSPR model may be valuable
      to analyze retention/selectivity data of closely related congeneric compound
      series, is illustrative and straightforward to implement. It is thus valuable for
      interpretation of retention mechanisms, while its utility for prediction of
      retention and enantioselectivity data is limited to compounds made up of groups
      included in the solute set used for deriving the increments. 

PMID- 24857034
TI  - Novel and sensitive reversed-phase high-pressure liquid chromatography method
      with electrochemical detection for the simultaneous and fast determination of
      eight biogenic amines and metabolites in human brain tissue.
AB  - A fast and simple RP-HPLC method with electrochemical detection (ECD) and ion
      pair chromatography was developed, optimized and validated in order to
      simultaneously determine eight different biogenic amines and metabolites in post
      mortem human brain tissue in a single-run analytical approach. The compounds of
      interest are the indolamine serotonin (5-hydroxytryptamine, 5-HT), the
      catecholamines dopamine (DA) and (nor)epinephrine ((N)E), as well as their
      respective metabolites, i.e. 3,4-dihydroxyphenylacetic acid (DOPAC) and
      homovanillic acid (HVA), 5-hydroxy-3-indoleacetic acid (5-HIAA) and 3-methoxy-4
      hydroxyphenylglycol (MHPG). A two-level fractional factorial experimental design
      was applied to study the effect of five experimental factors (i.e. the ion-pair
      counter concentration, the level of organic modifier, the pH of the mobile phase,
      the temperature of the column, and the voltage setting of the detector) on the
      chromatographic behaviour. The cross effect between the five quantitative factors
      and the capacity and separation factors of the analytes were then analysed using
      a Standard Least Squares model. The optimized method was fully validated
      according to the requirements of SFSTP (Societe Francaise des Sciences et
      Techniques Pharmaceutiques). Our human brain tissue sample preparation procedure
      is straightforward and relatively short, which allows samples to be loaded onto
      the HPLC system within approximately 4h. Additionally, a high sample throughput
      was achieved after optimization due to a total runtime of maximally 40min per
      sample. The conditions and settings of the HPLC system were found to be accurate
      with high intra and inter-assay repeatability, recovery and accuracy rates. The
      robust analytical method results in very low detection limits and good separation
      for all of the eight biogenic amines and metabolites in this complex mixture of
      biological analytes. 

PMID- 24857035
TI  - Synthesis of two thermo-responsive copolymers forming recyclable aqueous two
      phase systems and its application in cefprozil partition.
AB  - Aqueous two-phase systems are efficient purification methods for bioproducts.
      However, recovery difficulty of the copolymers forming aqueous two-phase systems
      becomes obstacle in scale-up application. In the study, novel recyclable aqueous
      two-phase systems have been developed by using two thermo-responsive copolymers,
      PNE and PVAm. Copolymer PNE was copolymerized by using N-isopropylacrylamide and
      ethyl methacrylate as monomers, and PVAm was synthesized by using N
      vinylcaprolactam and acrylamide as monomers. The lower critical solution
      temperatures of PNE and PVAm are 28.7 degrees C and 35.6 degrees C, respectively.
      The recoveries of both polymers can reach over 95%. The minimal and maximal
      partition coefficient of cefprozil was 0.33 at 50mM NH4F and 6.55 at 70mM LiCl.
      Two empirical equations were used to correlate with experimental binodal curve.
      Partition coefficients of cefprozil examined in the ATPS were correlated with tie
      line length and calculated partition coefficient. 

PMID- 24857036
TI  - Development of an innovative and "green" stir bar sorptive extraction-thermal
      desorption-gas chromatography-tandem mass spectrometry method for quantification
      of polycyclic aromatic hydrocarbons in marine biota.
AB  - There is a growing awareness of the need to reduce the negative impact of
      chemical analyses on the environment and to develop new eco-friendly and
      sustainable analytical methods without compromising performance. In this study,
      we developed a "green" analytical method enabling the accurate and simultaneous
      routine analysis of 21 polycyclic aromatic hydrocarbons (PAHs) in reduced
      quantities (100mg and 1g wet weight (WW)) of marine biota samples (fish muscle,
      mussel and oyster tissues) using alkaline digestion combined with stir bar
      sorptive extraction-thermal desorption-gas chromatography-tandem mass
      spectrometry (SBSE-GC-MS/MS). The innovative method provides good selectivity and
      specificity for most compounds. In 1gWW samples, limits of quantification (LOQs)
      ranged from 1 to 10MUg/kgWW in fish muscle and from 0.5 to 10MUg/kgWW in mussel
      tissue. The method enables most analytes to be quantified below the restrictive
      limits established by the European Commission (2 and 10MUg/kgWW in fish muscle
      and bivalve mollusc, respectively). Higher LOQs were obtained in 100mgWW samples
      ranging from 1 to 50MUg/kgWW. Recovery and linearity were assessed for all
      analytes. The results were satisfactory for most compounds with recoveries
      ranging from 94% to 117% in 1gWW mussel samples at spike concentration of
      10ng/gWW with standard deviation not exceeding 12%. However, results confirmed
      that the SBSE efficiency is affected by the complexity of biological matrices,
      especially for high molecular weight compounds in lipid-rich mussel tissue.
      Because of the matrix effects, matrix-matched calibrations were carried out.
      Validation was performed using the standard reference material 1974c with
      recovery ranging from 71% to 119% except for naphthalene, anthracene and
      benzo(e)pyrene that were therefore not validated. Overall, the developed method
      meets analytical validation criteria for most compounds. Thanks to the
      combination of alkaline digestion and SBSE, which greatly simplifies sample
      treatment and limits solvent use to ethanol, the developed method followed most
      green analytical chemistry principles. 

PMID- 24857037
TI  - Development of a polymeric ionic liquid coating for direct-immersion solid-phase
      microextraction using polyhedral oligomeric silsesquioxane as cross-linker.
AB  - A novel solid-phase microextraction (SPME) fiber was developed by chemical
      binding of a crosslinked polymeric ionic liquid (PIL) on the surface of an
      anodized Ti wire, and was applied in direct-immersion mode for the extraction of
      perfluorinated compounds (PFCs) from water samples coupled with high performance
      liquid chromatography-tandem mass spectrometry analysis. The PIL coatings were
      synthesized by using 1-vinyl-3-hexylimidazolium hexafluorophosphate as monomer
      and methylacryloyl-substituted polyhedral oligomeric silsesquioxane (POSS) as
      cross-linker via free radical reaction. The proposed fiber coating exhibited high
      mechanical stability due to the chemical bonding between the coating and the Ti
      wire surface. The integration of POSS reagent enhanced the organic solvent
      resistance of the coating. The parameters affecting the extraction performance of
      the fiber coating including extraction time, pH of solution, ionic strength and
      desorption conditions were optimized. The developed PIL-POSS fiber showed good
      linearity (R<0.998) between 0.1 and 50ngmL(-1) with method detection limits
      ranging from 0.005 to 0.08ngmL(-1) depending on the analyte, and with relative
      standard deviation for single-fiber repeatability and fiber-to-fiber
      reproducibility less than 8.6% and 9.5%, respectively. 

PMID- 24857038
TI  - Novel amphiphilic polymeric ionic liquid-solid phase micro-extraction membrane
      for the preconcentration of aniline as degradation product of azo dye Orange G
      under sonication by liquid chromatography-tandem mass spectrometry.
AB  - A novel amphiphilic polymeric ionic liquid membrane containing a hydrophilic
      bromide anion and a hydrophobic carbonyl group was synthesized in
      dimethylformamide (DMF) systems using the ionic liquid 1-butyl-3-vinylimidazolium
      bromide (BVImBr) and the methylmethacrylate (MMA) as monomers. The prepared
      amphiphilic ploy-methylmethacrylate-1-butyl-3-vinylimidazolium bromide (MMA
      BVImBr) was characterized by a scanning electron microscope and an infrared
      spectrum instrument. The results of solid-phase micro-extraction membrane (SPMM)
      experiments showed that the adsorption capacity of membrane was about 0.76MUgMUg(
      1) for aniline. Based on this, a sensitive method for the determination of trace
      aniline, as a degradation product of azo dye Orange G under sonication, was
      developed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The
      calibration curve showed a good linearity ranging from 0.5 to 10.0MUgL(-1) with a
      correlation coefficient value of 0.9998. The limit of quantification was 0.5MUgL(
      1). The recoveries ranged from 90.6% to 96.1%. The intra- and inter-day relative
      standard deviations were less than 8.3% and 10.9%. The developed SPMM-LC-MS/MS
      method was used successfully for preconcentration of trace aniline produced
      during the sonication of Orange G solution. 

PMID- 24857039
TI  - Development of a new high-performance liquid chromatography method with diode
      array and electrospray ionization-mass spectrometry detection for the metabolite
      fingerprinting of bioactive compounds in Humulus lupulus L.
AB  - The study was aimed at developing a new analytical method for the metabolite
      fingerprinting of bioactive compounds in Humulus lupulus L. (hop), together with
      a simple extraction procedure. Different extraction techniques, including
      maceration, heat reflux extraction (HRE), ultrasound-assisted extraction (UAE)
      and microwave-assisted extraction (MAE), were compared in order to obtain a high
      yield of the target analytes. Dynamic maceration for 30min with MeOH-HCOOH (99:1,
      v/v) as the extraction solvent provided the best result in terms of recovery of
      secondary metabolites. The analysis of hop constituents, including
      prenylflavonoids and prenylphloroglucinols (bitter acids), was carried out by
      means of HPLC-UV/DAD, HPLC-ESI-MS and MS(2), using an ion trap mass analyzer. An
      Ascentis Express C18 column (150mm*3.0mm I.D., 2.7MUm) was used for the HPLC
      analysis, with a mobile phase composed of 0.25% formic acid in both water and
      acetonitrile, under gradient elution. The method validation was performed to show
      compliance with ICH guidelines. The validated technique was successfully applied
      to the phytochemical analysis of ten commercial cultivars and twenty-three wild
      Italian hop genotypes, thus demonstrating to be a reliable and useful tool for
      the comprehensive multi-component analysis of hop secondary metabolites. 

PMID- 24857040
TI  - Concerted, rapid, quantitative, and site-specific dual labeling of proteins.
AB  - Rapid, one-pot, concerted, site-specific labeling of proteins at genetically
      encoded unnatural amino acids with distinct small molecules at physiological pH,
      temperature, and pressure is an important challenge. Current approaches require
      sequential labeling, low pH, and typically days to reach completion, limiting
      their utility. We report the efficient, genetically encoded incorporation of
      alkyne- and cyclopropene-containing amino acids at distinct sites in a protein
      using an optimized orthogonal translation system in E. coli. and quantitative,
      site-specific, one-pot, concerted protein labeling with fluorophores bearing
      azide and tetrazine groups, respectively. Protein double labeling in aqueous
      buffer at physiological pH, temperature, and pressure is quantitative in 30 min. 

PMID- 24857041
TI  - Discovery and preclinical development of vismodegib.
AB  - INTRODUCTION: Vismodegib is the first Hedgehog (Hh) pathway inhibitor approved in
      the US for the treatment of adults with metastatic or locally advanced basal cell
      carcinoma (BCC). It was approved by the US FDA on 30 January 2012, and by the
      European Commission on 12 July 2013, for the treatment of adult patients with
      symptomatic metastatic BCC, or locally advanced BCC inappropriate for surgery or
      radiotherapy. Vismodegib selectively inhibits the Hh signaling pathway, binding
      to and inhibiting a critical signal-transducing component of the pathway,
      Smoothened (SMO). Vismodegib was discovered by Genentech, Inc., under a
      collaboration agreement with Curis, Inc. AREAS COVERED: This article reviews the
      development of vismodegib from its discovery, preclinical pharmacology and
      validation to the clinical pharmacokinetics and validation in Phase I and II
      clinical investigations. We also provide a survey of other Hh pathway inhibitors
      in clinical development. EXPERT OPINION: The authors' experience in target-based
      drug discovery suggests that vismodegib's path to the clinic deserves some
      reflection to identify key steps that have contributed to its success. Targeting
      the Hh pathway with vismodegib blocks the abberant signaling caused by mutational
      inactivation of the negative regulator PTCH1 or mutational activation of SMO.
      Vismodegib gives physicians a treatment option for patients with locally advanced
      or metastatic BCC for whom surgery or radiation is not recommended.

PMID- 24857042
TI  - A complex fistula-in-ano presenting as a soft tissue tumor.
AB  - INTRODUCTION: Anorectal abscess and fistula are quite commonly encountered
      diseases. Both of these are the acute and chronic manifestations of the same
      entity. While abscess are thought to begin as an infection in the anal glands,
      their spreading into adjacent spaces results in a fistula formation. At many
      times this spread occurs in a complex pattern which is difficult to map and
      treat. PRESENTATION OF CASE: This paper describes a complex perianal fistula that
      presented as a painless benign lump in the upper outer quadrant of the right
      buttock. The lump initially thought to be a soft tissue swelling was later
      diagnosed to be a chronic abscess cavity extending medially toward the anal canal
      in the form of a complex fistulous tract. DISCUSSION: Complex perianal fistulas
      are difficult to treat and are prone to recurrences. Correct diagnosis and
      characterization of the fistula is essential to optimize the treatment. Clinical
      examination alone may not give a correct picture of the actual disease, thereby
      requiring radiological investigations like MRI. CONCLUSION: Although rare,
      sometimes common clinical conditions like fistula-in-ano may also present in
      complex manner. It is important to establish the diagnosis firmly and map the
      fistula properly before going in for surgery. Complexity of fistulas and improper
      mapping often leads to recurrences and other complications like incontinence.

PMID- 24857043
TI  - Two-dimensionally grown single-crystal silicon nanosheets with tunable visible
      light emissions.
AB  - Since the discovery of graphene, growth of two-dimensional (2D) nanomaterials has
      greatly attracted attention. However, spontaneous growth of atomic two
      dimensional (2D) materials is limitedly permitted for several layered-structure
      crystals, such as graphene, MoS2, and h-BN, and otherwise it is notoriously
      difficult. Here we report the gas-phase 2D growth of silicon (Si), that is cubic
      in symmetry, via dendritic growth and an interdendritic filling mechanism and to
      form Si nanosheets (SiNSs) of 1 to 13 nm in thickness. Thin SiNSs show strong
      thickness-dependent photoluminescence in visible range including red, green, and
      blue (RGB) emissions with the associated band gap energies ranging from 1.6 to
      3.2 eV; these emission energies were greater than those from Si quantum dots
      (SiQDs) of the similar sizes. We also demonstrated that electrically driven
      white, as well as blue, emission in a conventional organic light-emitting diode
      (OLED) geometry with the SiNS assembly as the active emitting layers. Tunable
      light emissions in visible range in our observations suggest practical
      implications for novel 2D Si nanophotonics.

PMID- 24857044
TI  - Human equilibrative nucleoside transporter 1 is not predictive for gemcitabine
      efficacy in advanced pancreatic cancer: translational results from the AIO-PK0104
      phase III study with the clone SP120 rabbit antibody.
AB  - BACKGROUND: The role of human equilibrative nucleoside transporter 1 (hENT1) as a
      predictive biomarker for gemcitabine efficacy in advanced pancreatic cancer
      remains unclear to date. PATIENTS AND METHODS: AIO-PK0104 was a German
      multicenter phase III trial comparing gemcitabine/erlotinib followed by
      capecitabine (GEC) with capecitabine/erlotinib followed by gemcitabine (CEG) in
      advanced pancreatic cancer. Archival tumour tissue from 169 of the 274 eligible
      study patients was available for a central and standardised immunohistochemistry
      staining for hENT1 expression using the SP120 rabbit monoclonal anti-hENT1
      antibody. Within a retrospective translational subgroup analysis, biomarker data
      were correlated with efficacy end-points. RESULTS: Thirty-nine out of 130 fresh
      cut slides were scored as hENT1(high) (30%), whereas 91 samples were classified
      as hENT1(low) (70%). For the 62 patients randomised to CEG median overall
      survival was estimated with 6.4 months in the hENT1(low) compared to 6.9 months
      in the hENT1(high) subgroup (Hazard Ratio (HR) 0.88, 95% confidence interval (CI)
      0.48-1.61, p=0.67). For the 68 patients randomised to GEC survival was 5.7 months
      in the hENT1(low) compared to 4.4 months in the hENT1(high) subgroup (HR 1.16,
      95% CI 0.69-1.96, p=0.57). In 101 patients receiving gemcitabine at any time
      during study treatment (either within the 1st- or 2nd-line setting) hENT1(low)
      cases had a median overall survival of 7.5 months and hENT1(high) patients an
      overall survival of 4.4 months (HR 1.30, 95% CI 0.84-2.03, p=0.24), respectively.
      CONCLUSION: Within this subgroup analysis from Arbeitsgemeinschaft Internistische
      Onkologie-pancreatic cancer (AIO-PK0104), no evidence supporting the use of hENT1
      as a predictive biomarker for gemcitabine efficacy in patients with advanced
      pancreatic cancer was found.

PMID- 24857045
TI  - Prognostic factors in malignant ovarian germ cell tumours (The Surveillance,
      Epidemiology and End Results experience 1978-2010).
AB  - PURPOSE: To evaluate the prognostic significance of age at diagnosis, extent of
      the disease (EOD) and socioeconomic (SES) and sociodemographic status (civil
      status, residency) on cause specific survival (CSS) in patients with malignant
      ovarian germ cell tumours (MOGCTs). To explore the cumulative incidence of a
      second cancer in 10-year MOGCT survivors. PATIENTS AND METHODS: 2541 patients
      with MOGCT, reported to the Surveillance, Epidemiology and End Results programme
      (1978-2010), were identified. The above mentioned prognostic factors were
      assessed separately for dysgerminoma and non-dysgerminoma, using Kaplan-Meier
      estimates and Cox Hazards Models, providing 95% confidence intervals (95% CI).
      RESULTS: Five-year CSS was 97% (95% CI, 96-98%), and 92% (95% CI, 91-93%),
      respectively for dysgerminoma, and non-dysgerminoma. Age >40 years at diagnosis
      and presence of metastases were significantly associated with cause specific
      mortality. Among non-dysgerminoma patients, decreasing SES (hazard ratio (HR),
      1.59; 95% CI, 1.11-2.28) and treatment before 1990 (HR, 2.65; 95% CI, 1.83-3.85)
      increased mortality. In the adjusted analysis, patients from Michigan were almost
      2.5 times more likely to die from MOGCT than patients from other states (HR,
      2.48; 95% CI, 1.17-5.25). Second cancer was diagnosed in 10% of 10-year survivals
      who underwent radiotherapy and in 2% of survivals in non-radiotherapy group
      (p=.002). CONCLUSIONS: Increased attention should be directed towards the
      management of elderly MOGCT patients and those with non-dysgerminoma histology
      with low SES. Radiotherapy should be avoided as much as possible. Survival
      differences related to residency may occur when new cancer treatments are
      introduced.

PMID- 24857046
TI  - Relationships between functional movement screen scores, maturation and physical
      performance in young soccer players.
AB  - The purpose of this study was to examine relationships between functional
      movement screen scores, maturation and physical performance in young soccer
      players. Thirty males (11-16 years) were assessed for maturation, functional
      movement screen scores and a range of physical performance tests (squat jump,
      reactive strength index protocol and reactive agility cut). Older players
      significantly outperformed younger participants in all tests (P < 0.05; effect
      sizes = 1.25-3.40). Deep overhead squat, in-line lunge, active straight leg raise
      and rotary stability test were significantly correlated to all performance tests.
      In-line lunge performance explained the greatest variance in reactive strength
      index (adjusted R(2) = 47%) and reactive agility cut (adjusted R(2) = 38%)
      performance, whilst maturation was the strongest predictor of squat jump
      performance (adjusted R(2) = 46%). This study demonstrated that variation of
      physical performance in youth soccer players could be explained by a combination
      of both functional movement screen scores and maturation.

PMID- 24857047
TI  - Urban vegetation for reducing heat related mortality.
AB  - The potential benefit of urban vegetation in reducing heat related mortality in
      the city of Melbourne, Australia is investigated using a two-scale modelling
      approach. A meso-scale urban climate model was used to quantify the effects of
      ten urban vegetation schemes on the current climate in 2009 and future climates
      in 2030 and 2050. The indoor thermal performance of five residential buildings
      was then simulated using a building simulation tool with the local meso-climates
      associated with various urban vegetation schemes. Simulation results suggest that
      average seasonal summer temperatures can be reduced in the range of around 0.5
      and 2  degrees C if the city were replaced by vegetated suburbs and parklands,
      respectively. With the limited buildings and local meso-climates investigated in
      this study, around 5-28% and 37-99% reduction in heat related mortality rate have
      been estimated by doubling the city's vegetation coverage and transforming the
      city into parklands respectively. 

PMID- 24857048
TI  - Characteristics of particulate matter (PM10) and its relationship with
      meteorological factors during 2001-2012 in Beijing.
AB  - Atmospheric pollution has become a significant challenge in Beijing metropolitan
      region, China. In this study, wavelet analysis and gray analysis were proposed to
      explore the temporal characteristics of particulate matter (PM10) and its
      relationships with meteorological factors during 2001-2012. The analysis
      indicated that air quality had got better significantly over the last decade. It
      was clearly interannual, seasonal, and monthly variation of atmospheric
      pollution, which represented that the air quality was the worst in spring, and
      got better in summer, subsequently tended to be more serious in autumn and
      winter. Generally atmospheric pressure was the most important meteorological
      feature influencing on PM10, followed by relative humidity and wind speed.
      However, the dominant meteorological factors influencing the atmospheric
      pollution were different in the four seasons. The results suggest that urban
      design and effective measures based on the relationship between meteorological
      factors and PM10 would be effective for improving atmospheric pollution. 

PMID- 24857049
TI  - [Treatment of juvenile scoliosis: Increasing the lengthening interval with the
      growing rod technique should not necessarily compromise thoracic growth].
AB  - OBJECTIVE: Serial lengthening with growing rods is recommended every six months
      for the treatment of early onset scoliosis. The objective of this study was to
      evaluate the longitudinal growth of the thorax and control of the deformity in a
      series of patients with juvenile scoliosis when time intervals were increased
      between lengthenings. MATERIAL AND METHODS: Retrospective study of eight
      patients. The following variables were measured: the Cobb angle, the apical
      vertebral translation, the coronal balance, thoracic T1-L1 length, thoracic T5
      T12 kyphosis, the proximal junctional kyphosis (PJK) angle, and the lumbar
      lordosis. Complications were recorded. RESULTS: Five idiopathic and three
      syndromic scoliosis cases (mean age 9.4 +/- 1.5 years) were evaluated. The
      initial surgery was followed by with an average of two distractions per patient.
      The mean time between distractions was 15.7 months. The final coronal main curve
      correction was 58%. Apical translation and coronal balance were improved and
      maintained after the surgeries. The thoracic (T1-L1) preoperative length was 20.8
      cm, the postoperative length was 24.4 cm, and the final length was 26 cm. At the
      end of follow-up, the average growth of the thorax was 5.2 cm. The preoperative
      (T5-T12) kyphosis was 33.5 degrees , and final 32.1 degrees . The change in the
      PJK angle was 2.5 degrees  at the end of follow-up. Most complications were
      related to instrumentation. Two superficial wound infections were encountered.
      CONCLUSION: For less severe juvenile scoliosis patients treated with growing
      rods, spacing out lengthenings over more than a year can decrease the number of
      surgeries, while still controlling the deformity and allowing longitudinal
      thoracic growth.

PMID- 24857050
TI  - Teaching successful medication administration today: more than just knowing your
      'rights'.
AB  - Medication administration is an important skill taught in undergraduate nursing
      programs. Student learning for this activity includes not only how to prepare and
      administer medications, but also includes interventions such as patient and
      family teaching. Students also are taught a series of 'rights' in order to
      prevent medication errors. There are many factors, both personal and system
      related, which contribute to medication errors in the health care environment.
      The purpose of this article is to provide strategies for teaching students
      medication administration that encompass the multiple factors involved to ensure
      safe practice. This opinion paper is based on the authors' considerable years of
      teaching experience (35 years clinical setting and classroom teaching with senior
      students in final year of baccalaureate program for 1st author and 16 years total
      for co-author). Recommendations put forth by the authors are: a) leveling
      students' clinical experiences in administering medications to include
      understanding of system factors, b) structured scenarios and purposeful linking
      of theory to clinical courses to advance students' knowledge and skills related
      to medication administration as they progress through the program, 3) revisiting
      math skills. 

PMID- 24857051
TI  - Laparoscopic Roux-en-Y gastric bypass for nonobese type II diabetes mellitus in
      Asian patients.
AB  - BACKGROUND: The beneficial role of laparoscopic Roux-en-Y gastric bypass (LRYGB)
      for type 2 diabetes mellitus (T2 DM) in morbidly obese patients has been
      established; however, there is scant evidence supporting its effectiveness in
      nonobese T2 DM Asian patients. The objective of this study was to evaluate the
      effect of LRYGB in nonobese T2 DM patients and elucidate the predictors of DM
      remission after one year follow-up. METHODS: Between June 2009 and May 2011,
      twenty-nine nonobese (body mass index (BMI)<27 kg/m(2)) Asian patients with T2 DM
      who underwent LRYGB were enrolled. All patients were prospectively followed up
      for one year. Baseline demographic characteristics, diabetic status, and clinical
      and biochemical data were collected preoperatively and one year after LRYGB. DM
      remission was defined as those with hemoglobin A1 c (HbA1 c)<6.5% without oral
      hypoglycemic drugs (OHA)/insulin. Outcomes in the DM remission group were
      compared with the nonremission group and analyzed. RESULTS: All clinical and
      biochemical parameters, except uric acid, were significantly improved. DM
      remission was achieved in eleven patients (37.9%) of whom five (45.5%) were male.
      Blood glucose, HbA1 c, c-peptide, homeostatic model assessment (HOMA-%B), and low
      density lipoprotein (LDL)-cholesterol were the significant variables in patients
      with DM remission; however, multiple logistic regression showed that only
      preoperative HOMA-%B (odds ratio (OR) = 1.13, 95% CI = 1.03-1.24) was a predictor
      for DM remission. Though no mortality was seen, the complication rate was 20.7%,
      of which 17.3% was related to marginal ulcers. CONCLUSION: LRYGB resulted in
      significant clinical and biochemical improvements in nonobese Asian patients,
      with HOMA-%B indicating beta-cell function as the main predictor of T2 DM
      remission. Appropriate patient selection with better beta-cell function and
      evidence from long-term follow-up may justify this therapeutic approach.

PMID- 24857052
TI  - Cancer log-kill revisited.
AB  - At the root of science lie basic rules, if we can discover or deduce them. This
      is not an abstract project but practical; if we can understand the why then
      perhaps we can rationally intervene. One of the unifying unsolved problems in
      physics is the hypothetical "Theory of Everything." In a similar vein, we can ask
      whether our own field contains such hidden fundamental truths and, if so, how we
      can use them to develop better therapies and outcomes for our patients. Modern
      oncology has developed as drugs and translational science have matured over the
      50 years since ASCO's founding, but almost from that beginning tumor modeling has
      been a key tool. Through this general approach Norton and Simon changed our
      understanding of cancer biology and response to therapy when they described the
      fit of Gompertzian curves to both clinical and animal observations of tumor
      growth. The practical relevance of these insights has only grown with the
      development of DNA sequencing promising a raft of new targets (and drugs). In
      that regard, Larry Norton's contribution to this year's Educational Book reminds
      us to always think creatively about the fundamental problems of tumor growth and
      metastases as well as therapeutic response. Demonstrating the creativity and
      thoughtfulness that have marked his remarkable career, he now incorporates a
      newer concept of self-seeding to further explain why Gompertzian growth occurs
      and, in the process, provides a novel potential therapeutic target. As you read
      his elegantly presented discussion, consider how this understanding, wisely
      applied to the modern era of targeted therapies, might speed the availability of
      better treatments. But even more instructive is his personal model-not only the
      Norton-Simon Hypothesis-of how to live and approach science, biology, patients
      and their families, as well as the broader community. He shows that with energy,
      enthusiasm, optimism, intellect, and hard work we can make the world better.
      Clifford A. Hudis, MD, FACP, 2013-2014 ASCO President. 

PMID- 24857053
TI  - Carpe Diem: time to seize the opportunity for cancer prevention.
AB  - In his plea for increased resources to implement cancer prevention strategies,
      Graham Colditz, MD, states that half or more of cancers in the U.S. and other
      high-income countries are preventable with information already available. He
      describes the data-driven possibilites: screening, vaccination, exercise, smoking
      cessation, sun protection, safe sexual practices, and moderate to no alcohol
      intake, as well as approaches to implement these strategies and makes a
      compelling case for using resources for this purpose. Dr. Colditz is Associate
      Director of Prevention and Control in the Alvin J. Siteman Cancer Center, and
      Niess-Gain Professor in the Department of Surgery at the Washington University
      School of Medicine. He received his PhD in epidemiology from Harvard University,
      and his Internal Medicine Training at the Royal Brisbane Hospital in Australia.
      Dr. Colditz has an enormous volume of publications, with over 800 original
      research articles. He has worked to identify lifestyle and environmental factors
      that affect people's health, and to develop and teach cancer prevention
      strategies at the individual and community levels. His research also powers a
      website-www.yourdiseaserisk.wustl.edu-that helps people assess their risk of
      developing cancer, diabetes and other diseases as well as suggesting ways to lead
      longer, healthier lives. His work is inspirational in combining excellent
      scientific investigation with dedication to making results available and useful
      to non-scientists. Gini F. Fleming, MD, Cancer Education Committee Chair. 

PMID- 24857054
TI  - Ovarian cancer: targeting the untargetable.
AB  - The premise that all tumors are targetable has been met with some controversy in
      the approach to epithelial ovarian cancer (EOC). Genomic analysis shows that
      these tumors (specifically, high-grade serous carcinomas) are genomically
      unstable and lack actionable driver mutations, much like HER2 in breast and
      gastric cancers. In this paper, Michael Birrer, MD, PhD, Massachusetts General
      Hospital, argues that the interpretation of genomic data in ovarian cancer
      requires a more thoughtful approach that necessitates a closer inspection of the
      data beyond the mere presence or absence of mutations. We must look at the
      extensive genomic alterations in DNA and, to understand more about the role of
      those genes affected by these changes, look beyond the tumor to the role of the
      stroma. As such, Dr. Birrer is arguing for the importance of translational
      research. This will be the key to precision medicine in ovarian cancer, as we
      approach drug discovery and improvements in treatment. Dr. Birrer is a world
      renowned scientist who has devoted his career to the study of gynecologic
      cancers. He has published over 200 papers and written over 27 book chapters and
      reviews, served on numerous leadership positions in gynecologic oncology
      (including as co-chair of the National Cancer Institute's Gynecologic Cancer
      Steering Committee), and remains a clinician-scientist with an active lab and an
      active clinic. His career trajectory has shown me it is possible to be engaged as
      a researcher and a clinician and the work he has done has already impacted the
      care of patients with ovarian cancer. Don S. Dizon, MD, ASCO Educational Book
      Editor. 

PMID- 24857055
TI  - Treating metastatic melanoma in 2014: what just happened and what is next?
AB  - In recent years the expectation related to treating patients with metastatic
      melanoma has changed. Three years ago, a diagnosis of metastatic melanoma was
      bleak; only a small number of patients would benefit from standard treatment and
      the reason for treatment benefit was often unknown, leaving physicians with
      limited options to help their patients. Today, just 3 years later, there are
      proven therapies that allow physicians to expect to shrink tumors and extend the
      lives of their patients after diagnosis. In this article, Paul B. Chapman, MD,
      Memorial Sloan Kettering Cancer Center, summarizes the recent advances in the
      field of metastatic melanoma and looks ahead to topics such as focusing on
      specificity, shutting down the ERK pathway, intermittent dosing, discovering
      driver mutations, individualizing checkpoint inhibition, and identifying
      rejection antigens to identify what should occur next in order to continue to
      improve outcomes for a larger population of patients with metastatic melanoma.
      Dr. Chapman's paper reminds us of the exciting progress that has been made while
      focusing on the work that is left in the field. Dr. Chapman is a physician
      scientist who specializes in diagnosing and treating melanoma that has
      metastasized to other parts of the body. Dr. Chapman led a clinical trial that
      paved the way, in part, to the approval of vemurafenib-a drug that targets a BRAF
      mutation that is present in approximately 50% of patients with metastatic
      melanoma. Dr. Chapman is one of five Memorial Sloan Kettering scientists to be
      appointed to a melanoma "Dream Team" that focuses on identifying potential
      therapies for metastatic melanoma patients who do not have the mutated form of
      the BRAF gene. Dr. Chapman is also a professor of medicine at the Weill Cornell
      Medical College and is the chair of the Melanoma Research Alliance Medical
      Advisory Board. In addition to the above, Dr. Chapman is a sought-after mentor
      for medical oncology fellows and has a current research interest in identifying
      novel means to more durably block signaling in the MAPK pathway in melanoma
      cells. Jedd Wolchok, MD, PhD, Scientific Program Committee Chair. 

PMID- 24857056
TI  - Fifty years of progress in radiation therapy for breast cancer.
AB  - Fifty years ago, radiation therapy (RT) was only used after mastectomy in
      patients with high-risk disease. The equipment, treatment planning, and treatment
      delivery were rudimentary compared to what is available today. In retrospect, the
      deleterious effects of the RT back then negated its benefits. The strategy of
      combining lesser surgery with RT (and adjuvant systemic therapy) has been
      successfully employed in breast-conserving therapy (BCT) and in avoiding axillary
      lymph node dissection in patients with 1 or 2 involved sentinel nodes. Local
      recurrence rates at 10 years following BCT are now similar to those following
      mastectomy. RT after breast-conserving surgery and after mastectomy has been
      demonstrated to not only decrease local-regional recurrence but also decrease
      distant metastases and improve long-term survival. The development of effective
      adjuvant systemic therapy has made RT not only more effective but also arguably
      more important. If systemic therapy is effective at addressing micro-metastatic
      disease, then obtaining local tumor control becomes even more important.
      Moderately hypofractionated RT (2.66 Gy per day) is just as safe and effective as
      conventional fractionation shortening BCT from 6 weeks to 3-4 weeks. Treatment is
      now given with multiple-energy linear accelerators, CT-based simulation, 3
      dimensional beam modulation for much greater dose homogeneity, on-board imaging
      for greater daily accuracy, and various techniques to reduce cardiac dose. 

PMID- 24857057
TI  - Lynch syndrome 101 (years, that is).
AB  - Lynch syndrome was described over a century ago but information on the medical
      consequences and optimal management of this disorder continue to amass and
      evolve. This brief overview highlights the gene-specific and site-specific cancer
      penetrance and management options for those with Lynch syndrome. 

PMID- 24857058
TI  - Role of hormones in cancer prevention.
AB  - Risk for breast cancer can be easily and rapidly assessed using validated,
      quantitative models. Multiple randomized studies show that the selective estrogen
      response modifiers (SERMs) tamoxifen and raloxifene can safely reduce the risk of
      invasive breast cancer in both pre- and postmenopausal women. Treatment resulted
      in a 38% reduction in breast cancer incidence, and 42 women would need to be
      treated to prevent one breast cancer event in the first 10 years of follow-up.
      Reduction was larger in the first 5 years of follow-up than in years 5 to 10, but
      no studies treated patients for longer than 5 years. Thromboembolic events were
      significantly increased with all SERMs, whereas vertebral fractures were reduced.
      Tamoxifen provides net benefit to all premenopausal women who are at increased
      risk, whereas raloxifene reduces risk nearly as much in postmenopausal women and
      offers increased safety. Both tamoxifen and raloxifene reduce the incidence of in
      situ cancers. Lasofoxifene reduced the risk of breast cancer by 79% in
      postmenopausal women with osteoporosis. The MAP3 trial showed a 65% reduction in
      the annual incidence of invasive breast cancer in postmenopausal women who were
      at moderately increased risk for breast cancer who took the aromatase inhibitor
      exemestane. The IBIS-II trial showed a 53% reduction in the risk of invasive
      breast cancer in postmenopausal women aged 40 to 70 who took the aromatase
      inhibitor anastrozole. Of the 50 million white women in the United States aged 35
      to 79, 2.4 million would have a positive benefit/risk index for chemoprevention. 

PMID- 24857059
TI  - The value of EGFRvIII as the target for glioma vaccines.
AB  - Malignant brain tumors continue to be rapidly progressive and resistant to most
      treatments. Even with state-of-the-art standard of care (surgery, chemotherapy,
      and radiotherapy) long-term survival in the last 80 years improved from 6 to 15
      months. Improved imaging has also likely contributed to prolonged survival.
      Immunotherapy for cancer dates back to publications from 1742. The central idea
      is that the immune system can detect and eliminate foreign antigens, either from
      infectious agents or tumors, and thus could be therapeutic in brain tumors.
      Recent introduction of immune modulators of cytotoxic T-lymphocyte antigen (CTLA)
      4 and programmed cell death 1/programmed cell death 1 ligand (PD-1/PDL1) add much
      excitement to this field. For brain tumors, there are several ongoing phase I and
      III trials to determine whether any of the current immunotherapy approaches can
      demonstrate activity in randomized, controlled double-blinded trials-with ongoing
      and historical trials presented in tables within the manuscript. Immunotherapy
      has explored the use of various types of antigens (obtained either from
      homogenates of patients' tumors or synthetically produced), and various
      immunization procedures and adjuvants. Glioma antigens have also been isolated
      from the patients' own tumor, then produced in vitro (for example the glioma
      antigen EGFRvIII), and used to immunize patients directly, or with carriers such
      as dendritic cells with or without additional adjuvants. Several of these
      practical approaches are currently in phase III trials. Remaining challenges are
      how to increase the percentage of complete responses and response duration, and
      the enigmatic absence of an almost total lack of adverse brain inflammation
      following immunization of brain tumor patients, as has been observed following
      immunization against brain antigens in other diseases, such as Alzheimer's
      Disease.

PMID- 24857060
TI  - Immunotherapy for glioma: from illusion to realistic prospects?
AB  - There is now evidence that the rules established for tumor immunology and
      immunotherapy in general are relevant for brain tumors. Treatment strategies
      explored have mainly involved vaccines using either tumor cells or components,
      and vaccines with defined synthetic peptides. This latter approach offers the
      advantage to select well-characterized antigens with selective or preferential
      expression on glioma. This is a prerequisite because collateral damage to the
      brain is not allowed. A second strategy which is reaching clinical trials is T
      cell therapy using the patients' own lymphocytes engineered to become tumor
      reactive. Tumor specificity can be conferred by forced expression of either a
      high-avidity T cell receptor or an antitumor antibody (the latter cells are
      called chimeric antigen receptors). An advantage of T cell engineering is the
      possibility to modify the cells to augment cellular activation, in vivo
      persistence and resistance to the tumor immunosuppressive milieu. A direct
      targeting of the hostile glioma microenvironment will additionally be required
      for achieving potent immunotherapy and various trials are assessing this issue.
      Finally, combining immunotherapy with immune checkpoint inhibitors and
      chemotherapy must be explored within rigorous clinical trials that favor constant
      interactions between the bench and bedside. Regarding immunotherapy for glioma
      patients, what was an unrealistic dream a decade ago is today a credible
      prospect. 

PMID- 24857061
TI  - Precision cancer medicine: the future is now, only better.
AB  - The promise of precision medicine for cancer is already being realized with the
      recent introduction of many targeted therapies, some with companion diagnostic
      tests that identify patients most likely to benefit from treatment. The utility
      of molecular profiling of cancer to identify actionable aberrations has been
      suggested by several small clinical trials conducted in patients with advanced
      cancer and by many anecdotes but is yet to be proven in well-designed,
      prospective, randomized trials. Several trials that will definitively test this
      strategy are now underway or soon to be launched. Melanoma, a disease once
      largely untreatable when metastatic, may be a paradigm for understanding how the
      molecular drivers of a disease can lead to highly effective targeted therapies,
      as well as for realizing the enormous therapeutic potential of unleashing the
      immune system against cancer to produce long-term disease control. Looking to the
      future, advanced omics technologies and computational techniques will enable
      assessment of not only genomic variants, as performed today, but also of pathway
      and network aberrations that will greatly facilitate selection of drug
      combinations likely to benefit specific patients. As our deepening understanding
      of tumor biology converges with rapid advances in measurement science and
      technology and computational analysis, we have an enormous opportunity to create
      a future for precision medicine in oncology that provides for highly specific,
      minimally toxic, and dramatically effective treatment for each patient. 

PMID- 24857062
TI  - National Cancer Institute's Precision Medicine Initiatives for the new National
      Clinical Trials Network.
AB  - The promise of precision medicine will only be fully realized if the research
      community can adapt its clinical trials methodology to study molecularly
      characterized tumors instead of the traditional histologic classification. Such
      trials will depend on adequate tissue collection, availability of quality
      controlled, high throughput molecular assays, and the ability to screen large
      numbers of tumors to find those with the desired molecular alterations. The
      National Cancer Institute's (NCI) new National Clinical Trials Network (NCTN) is
      well positioned to conduct such trials. The NCTN has the ability to seamlessly
      perform ethics review, register patients, manage data, and deliver
      investigational drugs across its many sites including both in cities and rural
      communities, academic centers, and private practices. The initial set of trials
      will focus on different questions: (1) Exceptional Responders Initiative-why do a
      minority of patients with solid tumors or lymphoma respond very well to some
      drugs even if the majority do not?; (2) NCI MATCH trial-can molecular markers
      predict response to targeted therapies in patients with advanced cancer resistant
      to standard treatment?; (3) ALCHEMIST trial-will targeted epidermal growth factor
      receptor (EGFR) and anaplastic lymphoma kinase (ALK) inhibitors improve survival
      for adenocarcinoma of the lung in the adjuvant setting?; and (4) Lung Cancer
      Master Protocol trial for advanced squamous cell lung cancer-is there an
      advantage to developing drugs for small subsets of molecularly characterized
      tumors in a single, multiarm trial design? These studies will hopefully spawn a
      new era of treatment trials that will carefully select the tumors that may
      respond best to investigational therapy. 

PMID- 24857063
TI  - Obligations of an academic and clinical oncologist: historical reflections.
AB  - Obligations are derived from one's core values-those fundamental, enduring,
      deeply held beliefs that guide one's everyday actions. Gandhi stated it more
      eloquently than I ever could: "Your beliefs become your thoughts, your thoughts
      become your words, your words become your actions, your actions become your
      habits, your habits become your values, your values become your destiny." So what
      are the obligations of the academic oncologist and clinician? I believe there are
      a few indubitable and fundamental obligations: professionalism, patient care,
      stewardship, maintenance of knowledge, productivity, and mentorship). I might add
      that I do not see these obligations as unique to the academician but rather
      applicable to all physicians. 

PMID- 24857064
TI  - Colorectal cancer: all hands on deck.
AB  - The past 50 years has seen substantial progress in our understanding of and in
      the management of colorectal cancer (CRC). Surveillance colonoscopy with
      resection of premalignant polyps has led to a decreased incidence of CRC even
      though compliance with the recommendations is suboptimal. Epidemiologic and
      genetic information allow us to identify individuals at risk for cancer and
      should allow us to prevent the disease in many individuals. Patients diagnosed
      with metastatic CRC live much longer than in the past, and some with metastatic
      disease are cured. This is attributed to many factors, including cross-sectional
      imaging that identifies metastases earlier, new surgical and radiation
      techniques, and numerous new chemotherapies. Higher resolution imaging modalities
      have improved the ability to find limited and resectable metastatic disease;
      surgical advances include laparoscopic-assisted procedures and safer and more
      extensive hepatic resection; and radiation techniques allow for higher dose and
      less morbidity. Biologic therapies have not yet been maximized, but we are
      learning when and where some should be used. Soon we expect to be staging
      patients by biologic and genetic characteristics rather than by gross pathology
      treating patients based on biologic features but preferably identifying people at
      risk and preventing CRC altogether. 

PMID- 24857065
TI  - The evolution of our molecular understanding of colorectal cancer: what we are
      doing now, what the future holds, and how tumor profiling is just the beginning.
AB  - Colorectal cancer (CRC) has been extensively molecularly characterized in recent
      years. In addition to the understanding of biologic hallmarks of the disease, the
      ultimate goal of these studies was to provide tools that could allow us to
      differentiate subgroups of CRC with prognostic and predictive implications. So
      far, subtype classification has been largely driven by well-described features:
      (1) defective mismatch repair resulting in higher mutation rate; (2) cellular
      proliferation along with chromosomal instability and copy number aberrations; and
      (3) an invasive stromal phenotype mainly driven by TGF-beta linked to epithelial
      mesenchymal transition. Recent studies have outlined the complexity of CRC at the
      gene expression level, confirming how heterogeneous the disease is beyond
      currently validated parameters, namely KRAS, BRAF mutations and microsatellite
      instability. In fact, adopting an extended mutation profile upfront, which
      includes nonrecurrent KRAS, NRAS, and PIK3CA gene variants, likely improves
      outcomes. In this article, we review the current trends of translational research
      in CRC, summarize ongoing genomically driven clinical trials, and describe the
      challenges for defining a comprehensive, robust, and reproducible disease
      classification system that links molecular features to personalized medicine. We
      believe that identification of CRC subtypes based on integrative genomic analyses
      will provide a better guide for patient stratification and for rational design of
      drugs targeting specific pathways. 

PMID- 24857066
TI  - Liver-directed therapies: surgical approaches, alone and in combination with
      other interventions.
AB  - When feasible, surgical resection is typically the preferred therapeutic option
      in patients with both primary and secondary hepatic malignancies. Improved
      patient selection, preoperative management, and advances in perioperative care
      have had a considerable effect on short-term and long-term outcomes following
      hepatic resection. Parenchymal transection of the liver can be performed using
      many different techniques such as digitoclasia, clamp crushing, vessel sealing
      system, harmonic scalpel, water-jet, Cavitron Ultrasonic Surgical Aspirator, or
      radiofrequency dissecting sealer. At the time of surgery, one of the main factors
      that influences postoperative morbidity and mortality is blood loss. Different
      techniques are used to decrease blood loss, such as the Pringle maneuver,
      selective ligation of the right, left, or smaller branches of the portal system;
      extrahepatic dissection; isolation; and transection of the hepatic artery and
      portal vein and the total vascular exclusion. Liver resection is on occasion
      accompanied by a concomitant procedure. Given that colorectal liver metastasis is
      a common indication for liver resection, colon resection is one of the more
      common concurrent procedures, but also surgical management of other disease in
      the lung or pancreas may sometimes be indicated. A subset of patients with
      primary or secondary liver malignancies may also require the addition of an
      ablative therapy to treat the extent of disease in the liver. Moreover,
      occasionally, hepatic resection takes place following intra-arterial therapy
      administration to the liver. Although many of these patients may benefit from
      surgical therapy, a multidisciplinary team approach remains critical. 

PMID- 24857067
TI  - Ampullary cancer: an overview.
AB  - Ampullary cancers are rare, accounting for only 0.2% of gastrointestinal cancers
      and approximately 7% of all periampullary cancers. They arise from the ampullary
      complex, distal to the confluence of the common bile and pancreatic duct (Fig.
      1). In contrast to other periampullary malignancies, true ampullary cancers
      present earlier in their disease course with symptoms that result from biliary
      obstruction. It is often difficult to distinguish primary ampullary cancers from
      other periampullary cancers preoperatively. In early stages, ampullary cancers
      are surgically treated, similar to pancreatic cancers, and typically with a
      pancreatico-duodenoectomy (or Whipple procedure). Because of their earlier
      presentation, resection rates for all patients are much higher than other
      periampullary carcinomas. Moreover, their prognosis tends to be better than those
      with other periampullary- and pancreatic-originating cancers. In patients with
      true ampullary cancer, there is very limited data to guide physicians on the
      choice of therapy, largely because of the rarity of the disease and the paucity
      of related research. Herein, we provide an overview of the biology, histology,
      current therapeutic strategies, and potential future therapies for carcinomas
      arising from the ampulla of Vater.

PMID- 24857068
TI  - Progress in the treatment of advanced prostate cancer.
AB  - The androgen receptor (AR) is the most significant target for patients with
      metastatic castration-resistant prostate cancer (mCRPC). There is now irrefutable
      evidence that the AR axis is functional in most patients throughout the history
      of prostate cancer, is crucial from diagnosis to death, even in patients who have
      received hormonal manipulation, and represents a relevant therapeutic target in
      all phases of the disease. The potential mechanisms of tumor escape after
      castration are multifold, with each mechanism today representing a therapeutic
      opportunity. Phase III trials have been able to demonstrate improved overall
      survival (OS), improved quality of life, decreased skeletal-related events, and
      other important clinical benefits in young and elderly patients. After the
      initial positive results with docetaxel chemotherapy in improving OS, further
      research has resulted in five new treatments in the past few years. Immunotherapy
      with sipuleucel-T, cabazitaxel chemotherapy, the androgen biosynthesis inhibitor
      abiraterone acetate, the antiandrogen enzalutamide, and the radioisotope radium
      223 have all been shown to improve OS in large-scale, well-conducted clinical
      trials. Proper understanding of mechanisms of resistance and of cross-resistance
      among these agents, sequencing, and combinations is now a priority. 

PMID- 24857069
TI  - Preparing for an epidemic: cancer care in an aging population.
AB  - The Institute of Medicine's (IOM) Committee on Improving the Quality of Cancer
      Care: Addressing the Challenges of an Aging Population was charged with
      evaluating and proposing recommendations on how to improve the quality of cancer
      care, with a specific focus on the aging population. Based on their findings, the
      IOM committee recently released a report highlighting their 10 recommendations
      for improving the quality of cancer care. Based on those recommendations, this
      article highlights ways to improve evidence-based care and addresses rising costs
      in health care for older adults with cancer. The IOM highlighted three
      recommendations to address the current research gaps in providing evidence-based
      care in older adults with cancer, which included (1) studying populations which
      match the age and health-risk profile of the population with the disease, (2)
      legislative incentives for companies to include patients that are older or with
      multiple morbidities in new cancer drug trials, and (3) expansion of research
      that contributes to the depth and breadth of data available for assessing
      interventions. The recommendations also highlighted the need to maintain
      affordable and accessible care for older adults with cancer, with an emphasis on
      finding creative solutions within both the care delivery system and payment
      models in order to balance costs while preserving quality of care. The
      implementation of the IOM's recommendations will be a key step in moving closer
      to the goal of providing accessible, affordable, evidence-based, high-quality
      care to all patients with cancer. 

PMID- 24857070
TI  - Molecular profiling and commercial predication assays in ovarian cancer: still
      not ready for prime time?
AB  - Short of early detection to allow curative primary intervention, the other major
      barrier to further success in treatment of ovarian cancers is matching the best
      treatment to the proper ovarian cancer type and to the individual patient. There
      are several decades of experience applying in vitro chemoresponse testing for
      solid tumors including ovarian cancer. This concept, first described in 1979, has
      yet to receive level one evidence supporting its application, despite the testing
      of numerous assays commercially as well as in academic centers and its use for
      tens of thousands of patients at a significant cost. The approach-rather than
      undergoing rigorous scientific examination-is now being muddied by the
      development of commercial molecular profiling assays from which treatment
      suggestions are provided. Molecular profiling as a research tool has added value
      to our understanding and treatment of patients with ovarian cancer. Morphologic
      and histochemical characterizations coupled now with increasing knowledge of
      ovarian cancer type-specific molecular patterns is improving our ability to
      properly diagnosis ovarian cancer type and thus guide therapy. With the exception
      of the role of germ-line and possibly somatic BRCA1 and BRCA2 mutations and their
      true predictiveness for probable response to poly(ADP-ribose) polymerase
      inhibition, molecular typing and profiling has yet to identify druggable
      molecular targets in ovarian cancer. Its use should be continued as a research
      and learning tool, and its results should be subjected to clinical trial
      validation. For very different reasons, neither chemoresponse assays nor
      molecular profiling are ready for prime time, yet. 

PMID- 24857071
TI  - Epstein-Barr virus as a paradigm in nasopharyngeal cancer: from lab to clinic.
AB  - Nasopharyngeal carcinoma (NPC) of the undifferentiated subtype remains endemic in
      southern China, with a peak incidence in this region approaching 30 cases per
      100,000 population per year. Despite advances in chemotherapy and radiation
      delivery techniques in localized disease, distant metastasis is still common and
      NPC remains the seventh leading cause of cancer death in the region. There is
      great need for early diagnosis, developing novel therapies, and identifying
      patients with localized disease at higher risk of future recurrence or metastasis
      to appropriately tailor their treatment and improve outcomes. Knowledge of the
      integral involvement of Epstein-Barr virus (EBV) in the pathogenesis of
      undifferentiated NPC has been of seminal importance in developing strategies to
      optimize disease management. The close association with EBV is being evaluated in
      multiple settings including screening of at-risk populations, disease
      prognostication, development of targeted therapies, optimizing adjuvant
      treatment, and early recurrence detection. These translational studies are likely
      to have an enormous effect on management of undifferentiated NPC and
      significantly improve the landscape of the disease in years to come. 

PMID- 24857072
TI  - Surgery in the HPV era: the role of robotics and microsurgical techniques.
AB  - Retrospective studies suggested that head and neck cancers associated with human
      papilloma virus (HPV) are more frequently cured than those caused by substance
      use. The Eastern Cooperative Oncology Group (ECOG) subsequently confirmed the
      observation in a prospective trial. Most HPV-initiated cancers arise in the
      oropharynx. Survival differences between patients with cancers caused by HPV and
      those caused by alcohol and tobacco use persist despite modern treatment. The
      impression that treatment intensification has resulted in improved survivorship
      may well be attributable to an increasing proportion of patients with cancers
      caused by HPV infection. Unsatisfactory results for cancers attributable to
      substance use and encouraging improvements in tumor control for patients with HPV
      initiated cancers have led to dissatisfaction with the current nonsurgical
      management paradigm. Ongoing advances in surgical techniques permit transoral
      resection of oropharyngeal cancers, thus limiting exposure-related morbidity and
      permitting ready recovery in terms of speech and swallowing. Transoral laser
      microsurgery (TLM) is increasingly employed and transoral robotic surgery (TORS)
      has dramatically popularized surgical treatment of oropharyngeal cancers.
      Resection affords the opportunity to increase local control at the primary site
      and surgical management of neck allows risk-based stratification of postoperative
      radiation therapy. Case series from several institutions show encouraging
      results. Transoral surgical resection is safe, can be undertaken with acceptable
      morbidity, and provides comparable locoregional control to that achieved with
      chemoradiation. Prospective trials for patients with HPV-initiated cancers, as
      well as those referable to substance use, are underway. 

PMID- 24857073
TI  - The rationale for collecting patient-reported symptoms during routine
      chemotherapy.
AB  - Patient-reported outcomes (PROs) such as symptoms and functional status are
      commonly measured in clinical trials. There is increasing interest to integrate
      PROs into routine clinical practice, for example during chemotherapy or
      postoperatively. There are several rationales for this. First, patient self
      reporting improves patient-clinic communication, symptom detection, and symptom
      control. Second, patient-reported data may be used for quality assessment. Third,
      aggregated patient-reported data can be informative in comparative-effectiveness
      research (CER). Of particular interest is an approach that employs electronic
      collection of PROs with interfaces to the electronic health record (EHR) and
      clinician alerts for concerning symptoms. Multiple systems have been developed in
      oncology with these characteristics. Barriers to implementation exist, such as
      cost, logistics, EHR interfacing, data representation, and data interpretation,
      but have been largely overcome. Missing data remain a concern, but backup data
      collection strategies can bring self-report compliance rates up to about 85% in
      unselected routine care patients with advanced cancers. Overall, including
      patient self-reporting in routine care enhances quality of care and patient
      satisfaction, and is expected to become more common in the future. American
      Society for Clinical Oncology (ASCO) has several ongoing initiatives to develop
      standards and clinical practice tools in this area. 

PMID- 24857074
TI  - Molecular monitoring and mutations in chronic myeloid leukemia: how to get the
      most out of your tyrosine kinase inhibitor.
AB  - The course of chronic myeloid leukemia (CML) and the response to treatment with
      tyrosine kinase inhibitors (TKIs) are best monitored and assessed using two
      molecular tests: the first is real-time quantitative reverse transcription
      polymerase chain reaction (RQ-PCR), which measures the size of residual disease
      that is expressed as BCR-ABL1% (the ratio between BCR-ABL1 and a control gene)
      and the other is mutational analysis by Sanger sequencing, which checks for the
      presence of BCR-ABL1 kinase domain point mutations. Both tests are technically
      demanding and require a high level of specialization and standardization. RQ-PCR,
      when performed on a regular basis, allows for the defining of molecular response
      (MR) levels as log reduction from a standardized baseline: major molecular
      response (MMR or MR(3)) that is the best predictor of survival; and the deeper
      molecular response (MR(4), MR(4.5), and MR(5)) that is necessary to enroll a
      patient in a trial aiming at treatment-free remission (TFR). Mutational analysis,
      to be performed in case of failure or warning by Sanger sequencing, allows for
      screening of the BCR-ABL1 kinase domain for mutations conferring resistance to
      TKIs. Since different mutations have different degrees of sensitivity to each of
      the currently available TKI, the knowledge of BCR-ABL1 kinase domain-mutation
      status is necessary for subsequent treatment choice. Optimal patient management
      requires that MR and mutational information be rationally interpreted at both the
      technical and at the biologic level, and put into context-therapeutic decisions
      also take into account other factors, such as age, comorbidities, side effects,
      compliance, and treatment-related complications. 

PMID- 24857076
TI  - Mantle cell lymphoma: biology, clinical presentation, and therapeutic approaches.
AB  - Mantle cell lymphoma is molecularly characterized by the chromosomal
      translocation t(11;14) (q13;q32) that results in a constitutional overexpression
      of the cell cycle regulator protein cyclin D1. Generally, the disease is
      characterized by rapid relapses and poor long-term outcome. However, a subset of
      patients with indolent disease has been identified. Randomized trials have
      demonstrated the superiority of dose intensified, cytarabine-containing induction
      with or without autologous stem cell transplantation in younger patients. In
      elderly patients, a rituximab-based maintenance has significantly prolonged
      progression-free and overall survival after treatment with rituximab,
      cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone (R
      CHOP). Unfortunately, the vast majority of patients will eventually relapse.
      Numerous molecular targeting strategies (bortezomib, lenalidomide, temsirolimus,
      and especially inhibitors of the B-cell receptor pathway) have achieved high
      response rates in phase II studies and should be strongly considered in relapsed
      disease. 

PMID- 24857075
TI  - 50 Years of progress in the systemic therapy of non-small cell lung cancer.
AB  - Non-small cell lung cancer constitutes 85% to 90% of lung cancer and is the most
      common cause of cancer death. Over the past 50 years, substantial progress has
      been made in all aspects of lung cancer including screening, diagnostic
      evaluation, surgery, radiation therapy, and chemotherapy. This review focuses on
      the advances in systemic therapy during this half century. 

PMID- 24857077
TI  - Where we were, where we are, where we are going: progress in multiple myeloma.
AB  - The celebration of the 50th anniversary of the founding of the American Society
      of Clinical Oncology provides the occasion to review the progress that has been
      made in the biology and treatment of multiple myeloma. With the advent of
      melphalan and cyclophosphamide in the early 1960s the median survival of patients
      with multiple myeloma more than doubled from 10 months to approximately 24
      months. Throughout multiple clinical trials in the 1970s and 1980s, melphalan and
      prednisone remained the gold standard, with a 3-year survival of 42%. The use of
      high-dose melphalan with autologous hematopoietic stem cell support provided an
      incremental advance in the 1990s. The outlook for patients was dramatically
      improved in the 2000s with the introduction of thalidomide analogs and proteasome
      inhibitors, so that the 3-year survival of patients treated in 2008 with
      melphalan and prednisone had increased to 66%. The 2010s are dominated by
      studying the optimal combination, sequence, and duration of therapies. These
      clinical advances have occurred along with our evolving understanding of the
      molecular pathogenesis of myeloma. Myeloma can be divided into two main groups:
      hyperdiploid, with multiple trisomies of odd-numbered chromosomes, and
      nonhyperdiploid, with recurrent immunoglobulin heavy chain gene translocations.
      Disease progression is associated with rearrangements of MYC, the most common
      mutation in myeloma, present in nearly half of patients. Genomic studies have
      highlighted marked subclonal heterogeneity that poses one of the main challenges
      to successful control of the disease. This problem will be addressed in future
      studies in the 2020s, which will include a focus on immunologic approaches such
      as monoclonal antibodies, checkpoint inhibitors, engineered T-cells, and novel
      immunomodulators. 

PMID- 24857078
TI  - Models of cancer survivorship health care: moving forward.
AB  - The population of cancer survivors in the United States and worldwide is rapidly
      increasing. Many survivors will develop health conditions as a direct or indirect
      consequence of their cancer therapy. Thus, models to deliver high-quality care
      for cancer survivors are evolving. We provide examples of three different models
      of survivorship care from a cancer center, a community setting, and a country
      wide health care system, followed by a description of the ASCO Cancer
      Survivorship Compendium, a tool to help providers understand the various models
      of survivorship care available and integrate survivorship care into their
      practices in a way that fits their unique needs. 

PMID- 24857079
TI  - Risk stratification for wilms tumor: current approach and future directions.
AB  - Wilms tumor, or nephroblastoma, has provided a paradigm for progressive
      improvement in clinical outcomes achieved through serial cooperative group
      studies. With modern surgery, chemotherapy, and radiation therapy approaches, the
      overall survival rate for patients with Wilms tumor has reached 90%. Remarkably,
      the increase in survival has been achieved with a reduction in therapy for most
      patient subgroups, leading not only to more survivors, but also to healthier
      survivors. A key contributor to improved outcomes has been the development of
      clinical and biologic prognostic markers that have enabled risk-directed therapy.
      Whereas the early cooperative group studies used only tumor stage for risk
      stratification, current Children's Oncology Group (COG) and International Society
      of Pediatric Oncology (SIOP) protocols employ a multitude of prognostic factors
      to guide therapy. Prognostic factors used in the current generation of COG
      studies include stage, histology, patient age, tumor weight, completeness of lung
      nodule response, and loss of heterozygosity at chromosomes 1p and 16q. Future COG
      studies seek to incorporate gain of chromosome 1q and methylation pattern of
      chromosome 11p15 into the risk classification schema. Prognostic factors used in
      the current SIOP studies include stage, histology, tumor volume, and
      responsiveness to therapy. Future SIOP studies seek to incorporate absolute
      blastemal volume and novel molecular markers for resistant blastema into the risk
      stratification approach. 

PMID- 24857080
TI  - Electronic health records (EHRs): supporting ASCO's vision of cancer care.
AB  - ASCO's vision for cancer care in 2030 is built on the expanding importance of
      panomics and big data, and envisions enabling better health for patients with
      cancer by the rapid transformation of systems biology knowledge into cancer care
      advances. This vision will be heavily dependent on the use of health information
      technology for computational biology and clinical decision support systems
      (CDSS). Computational biology will allow us to construct models of cancer biology
      that encompass the complexity of cancer panomics data and provide us with better
      understanding of the mechanisms governing cancer behavior. The Agency for
      Healthcare Research and Quality promotes CDSS based on clinical practice
      guidelines, which are knowledge bases that grow too slowly to match the rate of
      panomic-derived knowledge. CDSS that are based on systems biology models will be
      more easily adaptable to rapid advancements and translational medicine. We
      describe the characteristics of health data representation, a model for
      representing molecular data that supports data extraction and use for panomic
      based clinical research, and argue for CDSS that are based on systems biology and
      are algorithm-based. 

PMID- 24857081
TI  - Integrative oncology: an overview.
AB  - Integrative oncology, the diagnosis-specific field of integrative medicine,
      addresses symptom control with nonpharmacologic therapies. Known commonly as
      "complementary therapies" these are evidence-based adjuncts to mainstream care
      that effectively control physical and emotional symptoms, enhance physical and
      emotional strength, and provide patients with skills enabling them to help
      themselves throughout and following mainstream cancer treatment. Integrative or
      complementary therapies are rational and noninvasive. They have been subjected to
      study to determine their value, to document the problems they ameliorate, and to
      define the circumstances under which such therapies are beneficial. Conversely,
      "alternative" therapies typically are promoted literally as such; as actual
      antitumor treatments. They lack biologic plausibility and scientific evidence of
      safety and efficacy. Many are outright fraudulent. Conflating these two very
      different categories by use of the convenient acronym "CAM," for "complementary
      and alternative therapies," confuses the issue and does a substantial disservice
      to patients and medical professionals. Complementary and integrative modalities
      have demonstrated safety value and benefits. If the same were true for
      "alternatives," they would not be "alternatives." Rather, they would become part
      of mainstream cancer care. This manuscript explores the medical and sociocultural
      context of interest in integrative oncology as well as in "alternative"
      therapies, reviews commonly-asked patient questions, summarizes research results
      in both categories, and offers recommendations to help guide patients and family
      members through what is often a difficult maze. Combining complementary therapies
      with mainstream oncology care to address patients' physical, psychologic and
      spiritual needs constitutes the practice of integrative oncology. By recommending
      nonpharmacologic modalities that reduce symptom burden and improve quality of
      life, physicians also enable patients to play a role in their care. Critical for
      most patients, this also improves the physician-patient relationship, the quality
      of cancer care, and the well-being of patients and their families. 

PMID- 24857082
TI  - Radiotherapy for soft tissue sarcoma: 50 years of change and improvement.
AB  - Radiotherapy for soft tissue sarcoma (STS) has advanced significantly over the
      past 50 years. This review focuses briefly on the period from 1964 to 1999 and
      more substantially on the changes of the past 15 years, such as IMRT and image
      guided radiotherapy (IG-RT), especially when brought together (IG-IMRT) in the
      same planning and delivery process to treat localized STS. In particular, the
      introduction of IG-RT, target volume definitions for IG-RT, and review of recent
      clinical trials using IG-RT to treat localized STS in extremity will be reviewed.
      Finally, potential investigational agents combined with IG-RT to improve outcomes
      in patients with localized STS are discussed. 

PMID- 24857083
TI  - Surgical advances in bone and soft tissue sarcoma: 50 years of progress.
AB  - As the American Society of Clinical Oncology celebrates its 50th anniversary,
      physicians can appreciate the significant advances made in the treatment of
      patients with sarcoma. Historically, these rare tumors have garnered great
      interest in the medical profession, due to their ability to reach extraordinary
      size, resulting in substantial deformities and disabilities. Fortunately,
      advances in surgical management, which have occurred concurrently with advances
      in imaging, diagnostic techniques, and both local and systemic adjuvant
      treatments, offer patients diagnosed with sarcoma significant hope for successful
      treatment and the expectation of a meaningful quality of life. 

PMID- 24857084
TI  - Fifty years of advances in sarcoma treatment: moving the needle from conventional
      chemotherapy to targeted therapy.
AB  - Much of the progress in systemic therapy for sarcomas was accomplished in the
      first half of the last 5 decades. Various chemotherapeutic agents were tested in
      the 70s through the 80s and became part of the standard of care for this patient
      population. During the decade of the 90s, dose intensification became feasible as
      a result of improved supportive care and the availability of growth factors, thus
      maximizing the therapeutic potential of this class of agents. However, response
      rates and survival plateaued and it became obvious that newer and mechanistically
      different agents were needed to improve the therapeutic index and gain further
      enhancement of outcomes. Since early 2000, primarily inspired by the experience
      with imatinib in gastrointestinal stromal tumors (GISTs), several targeted
      therapies have been tested in sarcomas with modest success. The major limitations
      encountered include the lack of drivers and actionable targets for bone and soft
      tissue sarcomas with complex genomic profiles. Continued investigations and
      sequencing of larger numbers of these rare and heterogeneous malignancies could
      shed some light on a path toward improved outcomes. 

PMID- 24857085
TI  - Fifty years of systemic therapy for breast cancer: from one size fits all to
      tailored therapy.
AB  - Breast cancer treatment has evolved dramatically in the past 50 years. In
      addition to innovations in medical therapy-including widespread use of endocrine
      treatments, chemotherapy, and anti-HER2 agents-medical advances in genetic
      testing, imaging, and screening have revolutionized care. As profound as these
      changes in medical treatment have been, however, they are matched by a cultural
      transformation in the way society understands, discusses, and cares about breast
      cancer. Breast cancer has evolved from an unnamed affliction to a disease that is
      regularly featured on the front page of the newspapers, and is discussed in
      countless forums in traditional and social media. Clinical specialization in
      breast cancer among oncologists has given patients access to dedicated
      specialists around the country. These transformations will be highlighted through
      the analysis of a patient, Rachel Carson, who died 50 years ago from breast
      cancer. 

PMID- 24857086
TI  - Social media in clinical trials.
AB  - Social media has potential in clinical trials for pointing out trial issues,
      addressing barriers, educating, and engaging multiple groups involved in cancer
      clinical research. Social media is being used in clinical trials to highlight
      issues such as poor accrual and barriers; educate potential participants and
      physicians about clinical trial options; and is a potential indirect or direct
      method to improve accrual. We are moving from a passive "push" of information to
      patients to a "pull" of patients requesting information. Patients and advocates
      are often driving an otherwise reluctant health care system into communication.
      Online patient communities are creating new information repositories. Potential
      clinical trial participants are using the Twittersphere and other sources to
      learn about potential clinical trial options. We are seeing more organized
      patient-centric and patient-engaged forums with the potential to crowd source to
      improve clinical trial accrual and design. This is an evolving process that will
      meet many individual, institutional, and regulatory obstacles as we move forward
      in a changed research landscape. 

PMID- 24857087
TI  - Early phase trial designs and endpoints for targeted therapies in rare genotype
      subsets.
AB  - The primary goal of phase I dose-finding trials has been historically to
      understand the safety profile of a new treatment/regimen and establish the
      maximum tolerated dose (MTD) for further investigation in a specific tumor type.
      These designs hinged on the assumption that the highest safe dose is also likely
      to be the most efficacious dose. In the current era of stratified medicine and
      targeted therapies, these assumptions and designs are quickly becoming obsolete.
      Newer approaches to dose-finding designs are emerging with a focus on not just
      safety, but also an efficacy (clinical- or biomarker-based) measure to guide the
      determination of the "optimal" dose (not necessarily the MTD) model, as opposed
      to rule-based designs. These designs allow for flexibility in trial conduct, with
      improved precision in estimating the dose to take forward for further testing,
      patient selection/enrichment strategies to maximize the chance of therapeutic
      effect, and expansion cohorts to further understand the safety/efficacy of the
      agent and patient subsets most likely to benefit from the agent under
      investigation. Although advances in technology have enabled the possibility of
      using these newer approaches, the acceptance and integration of these approaches
      in practice can only be accelerated if it is developed in concert with a clinical
      paradigm. 

PMID- 24857088
TI  - ASCO's Community Research Forum: addressing challenges of community-based
      research from the grass roots.
AB  - ASCO's Community Research Forum is a solution-oriented venue for community
      research sites to overcome barriers to conducting clinical trials. The key
      objectives of the Forum are to (1) convene community-based researchers to
      identify challenges to conducting research that ASCO can address, (2) develop
      solution-oriented projects to address these challenges to facilitate clinical
      trial participation in community research settings, and (3) shape ASCO programs
      and policies to support members engaged in community research. The Community
      Research Forum holds an annual in-person meeting that convenes physician
      investigators, research administrators, research nurses, and clinical research
      associates from community-based research programs and practices. To meet
      identified needs, the Community Research Forum has developed the ASCO Clinical
      Trial Workload Assessment Tool and the ASCO Research Program Quality Assessment
      Tool. Both of these tools will be available to the public in 2014. The Forum is
      currently exploring the concept and potential metrics of a research certification
      program to formally assess community-based research programs, and to identify
      gaps and areas to improve the program in order to meet quality standards. The
      Community Research Forum's website aims to serve as a go-to resource for
      community-based physician investigators and research staff. The Community
      Research Forum will continue to provide a forum for community-based researchers
      to network, share challenges, and develop initiatives that provide solutions and
      facilitate the conduct of clinical trials. 

PMID- 24857089
TI  - Reforming the community research program: from Community Clinical Oncology
      Program to the National Cancer Institute Community Oncology Research Program.
AB  - Community research has been an integral and influential component of the National
      Research Program since the late 1970s. Institutionalization of community research
      in the Community Clinical Oncology Program (CCOP) has resulted in successful
      collaborations, meaningful accrual, achievement of quality standards, and
      translation of research into clinical practice. Although the national clinical
      trial system is undergoing modernization and improvement, the success of the CCOP
      and minority-based CCOP in cancer treatment, prevention, and control research is
      being extended to include cancer care delivery research in the newly created
      National Cancer Institute (NCI) Community Oncology Research Program. This article
      briefly presents a historic perspective of community involvement in federally
      sponsored clinical trials and introduces the continued involvement in the newly
      created NCI program. 

PMID- 24857090
TI  - Optimal management of the premenopausal patient with estrogen receptor-positive
      breast cancer.
AB  - Tamoxifen is the standard of care in the adjuvant treatment of premenopausal
      women with estrogen receptor-positive (ER+) breast cancer. Ovarian suppression
      (OS) is another method of endocrine therapy and has been shown to decrease the
      risk of recurrence and confer a survival advantage when used as the sole source
      of hormone therapy. However, there is no evidence that OS is superior to
      treatment with tamoxifen. Studies comparing OS with or without tamoxifen compared
      with chemotherapy have demonstrated comparable effects. There does not appear to
      be any additional benefit when OS is combined with chemotherapy, although there
      is a suggestion that there may be an effect in the subgroup of young women (aged
      younger than 40 years) who are least likely to experience chemotherapy-induced
      cessation of ovarian function. Interpretation of existing data is hampered by the
      lack of studies incorporating modern chemotherapy regimens and the absence of
      molecular analyses that would allow us to better define populations most likely
      to benefit from endocrine therapy. Last, the role of aromatase inhibitors (AI) in
      the premenopausal setting remains undefined. Two recent studies, SOFT and TEXT,
      aim to shed light on the effect of OS and AI in premenopausal ER+ breast cancer
      and are pending analysis. 

PMID- 24857091
TI  - The role of preclinical models in radiopharmaceutical therapy.
AB  - Radiopharmaceutical therapy (RPT) is a treatment modality that involves the use
      of radioactively labeled targeting agents to deliver a cytotoxic dose of
      radiation to tumor while sparing normal tissue. The biologic function of the
      target and the biologic action of the targeting agent is largely irrelevant as
      long as the targeting agent delivers cytotoxic radiation to the tumor.
      Preclinical RPT studies use imaging and ex vivo evaluation of radioactivity
      concentration in target and normal tissues to obtain biodistribution and
      pharmacokinetic data that can be used to evaluate radiation absorbed doses. Since
      the efficacy and toxicity of RPT depend on radiation absorbed dose, this quantity
      can be used to translate results from preclinical studies to human studies. The
      absorbed dose can also be used to customize therapy to account for
      pharmacokinetic and other differences among patients so as to deliver a
      prespecified absorbed dose to the tumor or to dose-limiting tissue. The
      combination of RPT with other agents can be investigated and optimized by
      identifying the effect of other agents on tumor or normal tissue radiosensitivity
      and also on how other agents change the absorbed dose to these tissues. RPT is a
      distinct therapeutic modality whose mechanism of action is well understood.
      Measurements can be made in preclinical models to help guide clinical
      implementation of RPT and optimize combination therapy using RPT. 

PMID- 24857092
TI  - Targeted alpha-particle immunotherapy for acute myeloid leukemia.
AB  - Because alpha-particles have a shorter range and a higher linear energy transfer
      (LET) compared with beta-particles, targeted alpha-particle immunotherapy offers
      the potential for more efficient tumor cell killing while sparing surrounding
      normal cells. To date, clinical studies of alpha-particle immunotherapy for acute
      myeloid leukemia (AML) have focused on the myeloid cell surface antigen CD33 as a
      target using the humanized monoclonal antibody lintuzumab. An initial phase I
      study demonstrated the safety, feasibility, and antileukemic effects of bismuth
      213 ((213)Bi)-labeled lintuzumab. In a subsequent study, (213)Bi-lintuzumab
      produced remissions in some patients with AML after partial cytoreduction with
      cytarabine, suggesting the utility of targeted alpha-particle therapy for small
      volume disease. The widespread use of (213)Bi, however, is limited by its short
      half-life. Therefore, a second-generation construct containing actinium-225
      ((225)Ac), a radiometal that generates four alpha-particle emissions, was
      developed. A phase I trial demonstrated that (225)Ac-lintuzumab is safe at doses
      of 3 MUCi/kg or less and has antileukemic activity across all dose levels
      studied. Fractionated-dose (225)Ac-lintuzumab in combination with low-dose
      cytarabine (LDAC) is now under investigation for the management of older patients
      with untreated AML in a multicenter trial. Preclinical studies using (213)Bi- and
      astatine-211 ((211)At)-labeled anti-CD45 antibodies have shown that alpha
      particle immunotherapy may be useful as part conditioning before hematopoietic
      cell transplantation. The use of novel pretargeting strategies may further
      improve target-to-normal organ dose ratios. 

PMID- 24857093
TI  - Alpha-emitter radium-223 in the management of solid tumors: current status and
      future directions.
AB  - Bone metastases, which are commonly seen in patients with advanced cancers, are a
      major cause of skeletal events, disability, and death. Radium-223 dichloride
      (radium-223; Xofigo, formerly Alpharadin), a first-in-class, alpha-emitting
      radiopharmaceutical that selectively targets bone metastases with high-energy
      short-range alpha-particles, has been approved for the treatment of patients with
      castration-resistant prostate cancer (CRPC) with symptomatic bone metastases and
      no known visceral metastases. Approval is based on results of the randomized
      phase III trial Alpharadin in Symptomatic Prostate Cancer (ALSYMPCA), in which
      radium-223 prolonged overall survival and time to first symptomatic skeletal
      event versus placebo among patients with CRPC with symptomatic bone metastases
      and was generally well tolerated, with low myelosuppression rates and manageable
      gastrointestinal adverse events. Long-term follow-up of the ALSYMPCA safety
      population showed that the incidence of myelosuppression remained low among
      patients treated with radium-223, with no additional safety issues of acute
      myelogenous leukemia, myelodysplastic syndrome, aplastic anemia, or primary bone
      cancer within approximately 1.5 years after treatment. The radium-223 overall
      survival benefit and low toxicity make it an effective, well-tolerated, and novel
      treatment option for CRPC and symptomatic bone metastases and opens the
      possibility of exploring radium-223 in the treatment of bone metastases from
      other cancers. A phase I clinical trial of patients with breast and prostate
      cancer with skeletal metastases demonstrated that radium-223 was safe and well
      tolerated at all therapeutically relevant dosages. Moreover, a phase IIa trial of
      patients with advanced breast cancer and progressive bone-dominant disease
      demonstrated that radium-223 targeted areas of increased bone metabolism and
      showed biologic activity. 

PMID- 24857094
TI  - Managing cumulative expectations in oncology: challenges and potential solutions.
AB  - The dedication of oncologists to their patients is undeniable. Patients given
      what can be a devastating diagnosis look to their physician for hope, guidance,
      and answers. The physician, in turn, must assimilate information from a
      staggering amount of resources and outlets and then form a plan that satisfies
      current practices and guidelines while still being consistent with the most
      current regulations set by a multitude of sources for oversight. Do all this for
      every patient in a time in which the number of new and continuing patients is
      ever increasing, and it is hardly surprising that the shocking overload can lead
      to physician burnout and, quite possibly, poorer patient care. Overload, be it
      information, task, knowledge, or expectation, is real, and to avoid succumbing,
      cancer care providers need to acknowledge that the problem exists by identifying
      the sources and admit that the problem of overload is out of control. Only then
      can providers begin to realize what can and can not be done, so that they can
      focus attention on what they are doing when they are doing it-an application of
      mindfulness. To take control of the avalanche of incoming information, providers
      need to make good use of filters, set time aside to evaluate inbound
      intelligence, and identify and (importantly) rely on a narrow set of trusted
      resources. Although strategies on coping with overloads abound, the physician
      needs to be diligent in applying the available options to keep burnout at bay. 

PMID- 24857095
TI  - Value of cancer care: ethical considerations for the practicing oncologist.
AB  - The value of cancer care has emerged at the center of a national discourse on
      fiscal responsibility and resource allocation. The cost of cancer care is rising
      at a higher pace than any other area of health care. As we struggle to address
      this unsustainable rise in cancer expenditures, oncology providers are forced to
      examine our practice patterns and our contributions to the overall health care
      cost burden. This article provides an oncologist-centered examination of our
      duties to individual patients and how they may seem at odds with our duties to
      society. It also discusses how oncology providers can do their part to contain
      health care costs while honoring their professional obligation to do their best
      for each patient. 

PMID- 24857096
TI  - Radiation oncology approaches in liver malignancies.
AB  - Radiation therapy plays an increasingly important role in the treatment of
      hepatic malignancies. There is convincing evidence of safety and efficacy
      employing brachytherapy (yttrium-90), three-dimensional conformal radiotherapy,
      intensity-modulated radiotherapy, stereotactic body radiotherapy (SBRT), and
      proton beam therapy (PBT) in all stages of primary and metastatic involvement in
      the liver. Technologic advances in tumor imaging, real-time tracking of moving
      targets during radiotherapy delivery, and superb radiation dose deposition
      control have enabled treatment of previously unapproachable lesions. Recently
      completed and ongoing clinical trials are refining optimal dose fractionation
      schedules for SBRT as monotherapy. Radioembolization as part of first-line
      therapy in metastatic colorectal tumors is being tested in large international
      trials combined with FOLFOX6 and bevacizumab, as well as in hepatocellular
      carcinoma with sorafenib. PBT is becoming more available as new facilities open
      in many countries providing particle beam therapy, which delivers unparalleled
      control of radiation dose close to critical structures. A major point of research
      is understanding how best to safely destroy tumors in the background of often
      fragile hepatic function from cirrhosis or heavily pretreated chemotherapy liver
      parenchyma. Fortunately, serious complications from radiotherapy are rare, acute
      toxicities are typically Common Terminology Criteria for Adverse Events v4.0
      grade 1-2, with consistent response rates of 50% to 97% in the modern era. 

PMID- 24857097
TI  - Current controversies in the stage-specific multidisciplinary management of
      pancreatic cancer.
AB  - Encouraging therapeutic approaches and treatment regimens for patients with both
      localized and metastatic pancreatic cancer have emerged over the last 5 years.
      However, these new strategies have brought important challenges and controversy.
      Clinical staging criteria are constantly evolving. No system has been uniformly
      adopted, limiting our understanding of the role of both pancreatectomy and
      neoadjuvant therapies for localized disease. The role of radiation therapy for
      the treatment of both resectable and unresectable pancreatic cancer remains
      unclear despite multiple prospective studies. Although two new systemic
      chemotherapy regimens have essentially transformed the care of many patients with
      metastatic cancer, criteria to guide their use in the general population have yet
      to be clearly established. Herein we provide an overview of these important
      controversies in the context of a broad update on the stage-specific management
      of patients with newly diagnosed pancreatic cancer. 

PMID- 24857098
TI  - The optimal duration and selection of adjuvant endocrine therapy for breast
      cancer: how long is enough?
AB  - Women with estrogen receptor (ER)+ early breast cancer (BC) are at continuing
      risk of relapse up to at least 15 years after diagnosis, despite being on
      adjuvant endocrine therapy for approximately 5 years. Extended adjuvant endocrine
      therapy with an aromatase inhibitor (AI) after 5 years of tamoxifen further
      reduces the risk of recurrence in postmenopausal women. More recently, continuing
      tamoxifen for 10 years has also been shown to further reduce the risk of
      recurrence compared with 5 years. There are no direct comparative data on the
      relative merits of extended tamoxifen compared with an AI; indirect evidence
      suggests that an AI may have increased efficacy but a greater adverse effect on
      quality of life. Results are awaited on the need for continuing front-line
      adjuvant AIs for more than 5 years. The next challenge is to determine which
      patients will benefit from this long-term treatment. Currently, tumor size, nodal
      involvement, and gene expression profile as measured by the PAM50 Risk of
      Recurrence (ROR) score have all been shown to have prognostic significance for
      late recurrence beyond 5 years. 

PMID- 24857099
TI  - A review of recent data in the treatment of gallbladder cancer: what we know,
      what we do, and what should be done.
AB  - Gallbladder cancer is now considered a distinct clinical entity, allowing for a
      separate analysis from that of other malignancies of the biliary tree. Symptoms
      related to a malignant tumor of the gallbladder include jaundice and abdominal
      pain, or a palpable abdominal mass that occurs in a late stage of the disease.
      The majority of patients with operable gallbladder cancer are diagnosed by
      cholecystectomy performed for presumed benign disease, mostly cholelithiasis, a
      clinical entity known as incidental gallbladder cancer. Given the poor prognosis
      if tumor invasion beyond the muscular layer and/or nodal metastasis is found,
      adjuvant treatments have been implemented, but few data are available to guide
      treatment decisions in this setting. For advanced disease, a multidisciplinary
      treatment approach including biliary drainage procedures and palliative support
      is needed in the management of this aggressive disease. Palliative chemotherapy
      with a combination of gemcitabine and cisplatin or oxaliplatin is the standard
      treatment based on the findings of two phase III trials that showed improved
      overall survival compared to single-agent chemotherapy and best supportive care.
      Several phase II studies have been reported investigating the role of targeted
      agents against EGFR, VEGF, HER2, and MEK. International collaboration to enhance
      our knowledge of gallbladder cancer should be encouraged. 

PMID- 24857100
TI  - New directions in perioperative management of locally advanced esophagogastric
      cancer.
AB  - Cancers of the esophagus arise as adenocarcinomas and squamous cell carcinomas;
      these represent distinct diseases, with differing prognosis, yet they are often
      studied in common trials. With surgery alone, 5 year survival for T2-T3N0 disease
      is less than 30% to 40%, and declines to less than 25% with nodal involvement.
      The CROSS randomly assigned patients to surgery alone or to weekly
      carboplatin/paclitaxel X 5 and 41.4 Gy concurrent radiotherapy, followed by
      surgery. Seventy-five percent of enrolled patients had adenocarcinoma.
      Preoperative combined-modality therapy improved R0 resection from 69% to 92% (p <
      0.001 and improved median survival from 24 months to 49.4 months (p < 0.003).
      This regimen reduced both locoregional recurrence (34% to 14%; p < 0.001) and the
      development of peritoneal carcinomatosis (14% to 4%; p < 0.001). Systemic
      perioperative therapy may have a greater effect on distant disease, the
      predominant mode of failure for these patients, and current trials compare
      preoperative chemoradiation with periooperative systemic therapy. PET scan
      response during preoperative chemotherapy without radiotherapy correlates with
      improvements in pathologic response and with improved survival. Nonresponse on
      early PET scan allows identification of patients for earlier surgery and
      discontinuation of ineffective preoperative chemotherapy, without survival
      detriment. There is no predictive benefit for early PET scan during the course of
      chemotherapy followed by chemoradiotherapy. The use of early PET scan during
      induction chemotherapy is being evaluated in CALGB/Alliance trial (NCT01333033).
      Molecular profiling has identified somatic gene mutations and pathways that may
      be oncogenic in upper gastrointestinal cancers. Potential targets include the
      epidermal growth factor receptor (EGFR), vascular endothelial growth factor
      receptor (VEGFR), HER2, mammalian target of rapamycin (mTOR), fibroblast growth
      factor receptor (FGFR), MEK, and others. Targeted therapies with known survival
      benefit in esophagogastric cancer are currently limited to trastuzumab for HER2
      overexpressing cancers, or ramicirumab. 

PMID- 24857101
TI  - Beyond stage I germ cell tumors: current status regarding treatment and long-term
      toxicities.
AB  - Approximately 20% to 40% of patients with germ-cell tumors (GCT) will need
      advanced medical treatment because of relapse or initial metastatic disease. The
      survival and recommended treatment for men with metastatic disease varies
      according to histology, primary and metastatic sites, and the level of
      prechemotherapy tumor markers. For patients with a good prognosis, three cycles
      of bleomycin, etoposide, and cisplatin (BEP) or four cycles of etoposide, and
      cisplatin are recommended. For patients with intermediate- and poor prognosis,
      four cycles of bleomycin, etoposide, and cisplatin remains the preferred
      treatment option, although a switch to a more intensive regimen can be considered
      a new alternative. A major advance in salvage therapy for GCT in the last 5 years
      was the development of a new risk classification system. Initial salvage
      treatment includes both high-dose chemotherapy and standard-dose chemotherapy.
      There is clear consensus that patients with residual masses larger than 1 cm
      should undergo postchemotherapy retroperitoneal lymph node dissection (PC-RPLND);
      however, the role of PC-RPLND in patients with serologic and radiographic
      complete response to first-line chemotherapy is controversial. The rationale for
      PC-RPLND in patients with small residual masses is discussed, and only a small
      minority of advanced nonseminoma GCT (NSGCT) patients are suitable candidates for
      observation after first-line chemotherapy. Post-treatment long-term toxicity has
      emerged as an important issue for GCT survivors. Examples of late effects are
      secondary nongerm-cell cancers and cardiovascular disease, which represent the
      most severe and potentially life-threatening effects of cancer treatment. Follow
      up of cancer survivors should include recommendations for maintaining a healthy
      lifestyle to reduce the risk of serious long-term and late effects of treatment. 

PMID- 24857102
TI  - The geriatrics and genetics behind bladder cancer.
AB  - Bladder cancer is a disease of older patients who often have multiple
      comorbidities. Although cisplatin-based combination chemotherapy is the standard
      of care in the neoadjuvant and metastatic settings, outcomes remain poor, and
      approximately half of patients are ineligible for cisplatin where treatment
      options are severely limited. Recent comprehensive genome sequencing studies have
      defined the mutational spectra of high-grade urothelial carcinoma of the bladder.
      Although there is a high prevalence of potentially actionable genomic
      alterations, whether these events represent true oncogenic vulnerabilities has
      yet to be confirmed. Given the demographics and genetics, we propose that bladder
      cancer represents an ideal model to study the potential of targeted therapy in
      older patients who are too often unable to receive cisplatin-based therapy and
      where novel treatment strategies are desperately needed. 

PMID- 24857103
TI  - Molecular characterization and clinical utility of circulating tumor cells in the
      treatment of prostate cancer.
AB  - Circulating tumor cells (CTCs) are rare cancer cells that can be detected in the
      blood of patients with solid malignancies. The Veridex CellSearch Assay was
      analytically and clinically validated, and has received U.S. Food and Drug
      Administration (FDA) clearance for the enumeration of CTCs in breast, colorectal,
      and prostate cancer. A number of alternative assays, with potential advantages,
      are currently undergoing clinical and/or analytic validation before their routine
      use can be established. In prostate cancer, high pretreatment CTC counts have
      been associated with worse survival, and changes in CTC counts in response to
      treatment have been established as indicators of response to treatment.
      Additional analyses are ongoing to establish the value of CTC counts as a
      surrogate of survival in prospective, phase III trials, which could influence the
      process of drug development and regulatory approval. Additionally, CTCs have a
      potential role in the molecular characterization of prostate cancer, serving as
      "liquid biopsies" to determine the molecular characteristics of the disease. The
      study of androgen receptor (AR) mutations or amplification, chromosomal
      rearrangements, or the determination of DNA repair biomarkers has been evaluated
      in clinical trials. CTCs have a wide range of potential applications, from their
      prognostic use in stratification of patients in clinical trials or the assessment
      of response to treatment, to the pharmacodynamic evaluation of novel agents, or
      the discovery and use of predictive biomarkers that can aid in the development of
      personalized medicine. 

PMID- 24857104
TI  - Building on Prostate Cancer Working Group 2 to change the paradigm from
      palliation to cure.
AB  - Developing systemic therapies for advanced prostate cancer has significant
      challenges, including the difficulty of assessing baseline disease status,
      disease heterogeneity, and the lack of standards for assessing treatment effects
      that reliably reflect clinical benefit. To address these issues, the Prostate
      Cancer Working Group (PCWG2) took three actions. First, the Group incorporated a
      prostate cancer clinical states model framework for patient management and drug
      development. Second was establishing a two-objective paradigm in which trials are
      designed to evaluate a drug's ability to either (a) control, relieve, or
      eliminate present disease manifestations or (b) prevent or delay future disease
      manifestations. Third was the development of consensus criteria for eligibility,
      outcomes, and reporting in prostate cancer clinical trials. Now that the
      molecular interrogation of prostate cancer has led to a more complex
      understanding of disease biology, drug development has transitioned from
      evaluating cytotoxic agents with activity in multiple tumor types to the rational
      development of therapies targeting different aspects of the malignant process. In
      addition, the current availability of multiple therapies for advanced prostate
      cancer that prolong life brings a new mandate: that we define, validate, and
      qualify predictive biomarkers of sensitivity to guide treatment selection and
      establish endpoints short of survival that can lead to drug approval.
      Optimization of outcomes in future trials will require revised guidance on how to
      align clinically relevant objectives and eligibility with an evolving disease
      framework. 

PMID- 24857105
TI  - Treating the two extremes in renal cell carcinoma: management of small renal
      masses and cytoreductive nephrectomy in metastatic disease.
AB  - The incidental renal mass represents a heterogeneous group that contains both
      benign and malignant pathologies. The majority of renal cell carcinomas are
      discovered incidentally, without the presence of symptoms directly related to the
      mass, and are closely associated with the term small renal masses because of the
      discovery before the onset of symptoms. In general, small renal masses are
      defined as 4 cm or smaller, and may account for greater than half of renal cell
      carcinoma diagnosis. The use of renal mass biopsy may offer additional
      pathological information but the clinician must be reminded of the technical and
      diagnostic limitations of renal mass biopsy. Patient-dependent factors, such as
      life expectancy and comorbidities, guide the management of small renal masses,
      which include active surveillance, partial nephrectomy, radical nephrectomy, and
      ablative techniques (cryoablation and radiofrequency ablation). Partial
      nephrectomy has demonstrated durable oncologic control for small renal masses
      while preserving renal function and, if feasible, is the current treatment of
      choice. In the other extreme of the renal cell carcinomas spectrum and in the
      presence of metastatic disease, the removal of the renal primary tumor is termed
      cytoreductive nephrectomy. Two randomized trials (SWOG 8949 and EORTC 30947) have
      demonstrated a survival benefit with cytoreductive nephrectomy before the
      initiation of immunotherapy. These two studies have also been the motivation to
      perform cytoreductive nephrectomy in the targeted therapy era. Currently, there
      are two ongoing randomized prospective trials accruing to investigate the timing
      and relevance of cytoreductive nephrectomy in the contemporary setting of
      targeted therapy. 

PMID- 24857106
TI  - New agents and new targets for renal cell carcinoma.
AB  - The vascular endothelial growth factor (VEGF) pathway blockers and mammalian
      target of rapamycin (mTOR) inhibitors have dramatically improved the treatment
      options and outcome for patients with advanced renal cell carcinoma (RCC).
      However, because the vast majority of patients will still succumb to their
      disease, novel treatment approaches are still necessary. Efforts to identify
      novel therapeutic target treatments are focused on better understanding unique
      aspects of tumor cell biology guided the Cancer Genome Atlas analyses and the
      interaction of the tumor with its microenvironment. Areas of promising
      investigation include a) the identification of mechanisms of acquired resistance
      to VEGF pathway inhibition and developing agents targeting these in combination
      with VEGF receptor (VEGFR) pathway blockade; b) the identification of novel
      therapeutic targets, particularly for patients with VEGF pathway blocker
      refractory disease; and c) the development of novel immunotherapies, particularly
      those involving checkpoint inhibitors used alone or in combination with other
      immunotherapies of VEGF pathway blockers. Specific targets or agents of interest
      include angiopoietins (trebaninib), c-Met (cabozantinib), activin receptor-like
      kinase-1 (ALK-1; dalantercept), interleukin (IL)-8, and HDM2 for acquired
      resistance to VEGF pathway inhibition; hypoxia inducible factor-2 alpha (HIF-2
      alpha), TORC1/2, and the Hippo pathway for novel targets, and PD1 and PDL1
      antibodies given either alone or in combination with other checkpoint inhibitors,
      other immunotherapies, or VEGF pathway blockers for novel immunotherapies. In
      addition, the application of genetic, immunologic, or other biomarkers developed
      in the context of this research has the potential to select patients with
      specific tumor types for therapy targeted to specific vulnerabilities within the
      tumor or tumor microenvironment. Together, these developments should enable the
      transition to a new era of rational and more effective therapy for patients with
      advanced RCC. 

PMID- 24857107
TI  - Improving outcomes in metastatic clear cell renal cell carcinoma by sequencing
      therapy.
AB  - Targeted agents have substantially improved outcomes in metastatic clear cell
      renal cell carcinoma. However, due to multiple mechanisms of evasive resistance,
      almost all patients progress at some point and may require subsequent therapies.
      Various agents have been explored after failure of first-line treatment in
      randomized clinical trials. However, so far few questions about the optimal
      sequence have been answered. Both everolimus and axitinib have been considered
      standard of care after failure of first-line VEGF-TKI; sorafenib has been
      proposed as an additional option. In clinical practice, several factors may
      influence the choice of subsequent treatment: these include considerations on
      appropriate drug exposure in first-line, gained insights on prognostic and
      predictive factors as well as mechanisms of resistance. Once the decision in
      second-line has been made and treatment has been initiated, treating physicians
      may already be challenged by the question of what to offer in third- and later
      lines. Treatment beyond second-line treatment isn't supported by strong evidence,
      and at this stage of disease, retrospective reports on rechallenge may help to
      guide decisions. In addition, local treatment approaches including metastasectomy
      and stereotactic radiosurgery may help to optimize outcomes in all treatment
      lines. 

PMID- 24857108
TI  - Personalizing therapy for older adults with lymphoid malignancies: options and
      obstacles.
AB  - Increasing age is both a risk factor for and a negative prognostic factor in
      lymphoid malignancies. The disparities in outcomes between older and younger
      adults with lymphoid malignancies may reflect age-related differences in
      treatment and in biology of disease. Lymphomas in older adults are biologically
      more aggressive. Only small age-related differences in the frequency of
      cytogenetic abnormalities are seen in multiple myeloma. No major differences in
      the biology of chronic lymphocytic leukemia (CCL) are seen across the age
      spectrum. Chemotherapy and immunotherapy in older adults with lymphoid
      malignancies are marked by greater vulnerability to toxicity of therapy.
      Excessive toxicity can result in poorer outcomes, either directly through
      treatment-related mortality, or through decreased dose intensity. Thus, new
      approaches to predict toxicity of therapy and stratified treatment algorithms
      based on risk of toxicity are needed. Herein we detail some of the promising
      approaches to predicting toxicity and tailoring treatment for older adults with
      lymphoid malignancies. 

PMID- 24857109
TI  - Endocrine therapy toxicity: management options.
AB  - Treatment with adjuvant endocrine therapy, including tamoxifen and the aromatase
      inhibitors, has resulted in notable improvements in disease-free and overall
      survival for patients with hormone receptor-positive breast cancer. Despite their
      proven benefit, however, adherence to and persistence with the medications is
      poor in part because of bothersome side effects that can negatively affect
      quality of life. Retrospective analyses have identified possible predictors of
      development of toxicity. Reports have also suggested that development of toxicity
      may be a biomarker of better response to therapy. In addition, there has been
      considerable research investment into the management of these side effects, which
      may lead to improved adherence and persistence with therapy. However, although
      notable advances have been made, much more remains to be done to provide patients
      with truly personalized therapy for hormone receptor-positive breast cancer. 

PMID- 24857110
TI  - Current approaches to the management of bladder cancer in older patients.
AB  - Bladder cancer is largely a disease of older adults, with nearly half of
      diagnoses occurring in those older than age 75. This has led to a disconnect
      between the efficacy and effectiveness of various treatment strategies. For
      example, surgical removal of the bladder is a potentially curative approach to
      muscle-invasive disease, although the large single-center and multicenter series
      that have established the efficacy of this approach include only a small
      proportion of older patients. Similarly, clinical trials that have established
      optimal chemotherapeutic regimens for use in the perioperative and metastatic
      settings comprise largely younger patients. Extrapolating the available evidence
      to the population of older patients with bladder cancer requires careful
      assessment of an individual patient's functional status and comorbidities to
      estimate the likelihood of treatment-related harms. This should be coupled with
      an understanding of an individual patient's goals of therapy, independence,
      estimated longevity, and social support to facilitate a shared medical decision
      regarding treatment. The use of validated approaches to geriatric assessment may
      refine risk stratification in older adults, although practical challenges have
      prevented uniform adoption in routine clinical practice. 

PMID- 24857112
TI  - Can we maximize both value and quality in gynecologic cancer care? A work in
      progress.
AB  - Value is defined as desirable health outcomes achieved per monetary unit spent.
      Comparative effectiveness research and cost-effectiveness research are methods
      that have been developed to quantify effectiveness and value to inform management
      decisions. In this article we review the comparative and cost-effectiveness
      literature in the field of ovarian cancer treatment. Studies have shown that
      improved ovarian cancer survival is associated with complete primary surgical
      cytoreduction, with treatment at high volume facilities by subspecialist
      providers (gynecologic oncologists) and with National Comprehensive Cancer
      Network (NCCN) guideline-adherent care in both surgical staging and chemotherapy
      regimens. Intraperitoneal/intravenous chemotherapy (compared with intravenous
      alone) has been associated with improved survival and cost-effectiveness.
      Bevacizumab for primary and maintenance therapy has been found to not be cost
      effective (even in selective subsets) despite a small progression-free survival
      (PFS) advantage. For platinum-sensitive recurrent ovarian cancer, secondary
      cytoreduction and platinum-based combinations are associated with improved
      overall survival (OS); several platinum-based combinations have also been found
      cost-effective. For platinum-resistant recurrence, single agent therapy and
      supportive care are cost-effective compared with combination therapies. Although
      little prospective clinical research has been done around end-of-life care, one
      study reported that for platinum-resistant ovarian cancer, palliative
      intervention would potentially reduce costs and increase quality adjusted life
      years compared with usual care (based on improvement in quality of life [QOL]).
      Overall, cost comparisons of individual chemotherapy regimens are highly
      dependent on market prices of novel therapeutic agents. 

PMID- 24857111
TI  - Patient-derived xenograft models in gynecologic malignancies.
AB  - In the era of targeted therapies, patients with gynecologic malignancies have not
      yet been major beneficiaries of this new class of agents. This may reflect the
      fact that the main tumor types-ovarian, uterine, and cervical--are a highly
      heterogeneous group of cancers with variable response to standard chemotherapies
      and the lack of models in which to study the diversity of these cancers. Cancer
      derived cell lines fail to adequately recapitulate molecular hallmarks of
      specific cancer subsets and complex microenvironments, which may be critical for
      sensitivity to targeted therapies. Patient-derived xenografts (PDX) generated
      from fresh human tumor without prior in vitro culture, combined with whole genome
      expression, gene copy number, and sequencing analyses, could dramatically aid the
      development of novel therapies for gynecologic malignancies. Gynecologic tumors
      can be engrafted in immunodeficient mice with a high rate of success and within a
      reasonable time frame. The resulting PDX accurately recapitulates the patient's
      tumor with respect to histologic, molecular, and in vivo treatment response
      characteristics. Orthotopic PDX develop complications relevant to the clinic,
      such as ascites and bowel obstruction, providing opportunities to understand the
      biology of these clinical problems. Thus, PDX have great promise for improved
      understanding of gynecologic malignancies, serve as better models for designing
      novel therapies and clinical trials, and could underpin individualized, directed
      therapy for patients from whom such models have been established.

PMID- 24857113
TI  - Management of vulvar and vaginal melanomas: current and future strategies.
AB  - Melanomas arising in the vulva and vagina are rare and therefore there is minimal
      data specific to these malignancies. Data are often extrapolated from other
      cutaneous melanomas, which may or may not be appropriate. Surgery remains the
      primary treatment modality at initial diagnosis and in select recurrent cases.
      Wide local excision of the primary lesion not requiring an exenteration, along
      with sentinel lymph node (SLN) mapping, should be routinely considered in vulvar
      melanomas. Local excision and SLN mapping is difficult and often not considered
      for vaginal melanomas. Primary exenterative procedures should not be routinely
      offered. In locally advanced cases potentially requiring an exenterative
      procedure, radiation therapy with or without concurrent immunotherapy is a
      consideration. The role of adjuvant therapy remains unclear. Surgery or radiation
      therapy can be considered in recurrent cases. Systemic chemotherapy agents have a
      modest response rate with associated poor survival outcomes. Novel
      immunotherapeutic and targeted agents have been reported to improve survival in
      melanoma and should be considered in cases of vulvovaginal melanoma. All cases
      should be tested for at least c-KIT and BRAF V600E mutations. Patients with
      vulvovaginal melanomas should be strongly encouraged to participate in clinical
      trials. 

PMID- 24857114
TI  - Novel approaches to improve the treatment of rare gynecologic cancers: research
      opportunities and challenges.
AB  - More than 50% of all gynecologic cancers can be classified as rare tumors
      (defined as an incidence of fewer than six per 100,000). Improved understanding
      of the molecular pathogenesis of tumors increases the proportion of rare tumors
      and creates challenges in optimizing the design of clinical trials. Novel trial
      designs are needed to take forward the development of new treatments in rare
      tumors. This requires international partnerships, harmonization of treatment, and
      collaboration to overcome the regulatory barriers to conducting international
      trials. Although randomized trials can be done in many tumor types, there are
      some for which conducting even single-arm studies may be challenging. For these
      tumors, robust collection of data through national and/or international
      registries could lead through audit to improvements in the treatment of rare
      tumors. 

PMID- 24857115
TI  - Survivorship in gynecologic cancer: enduring the treatment toward a new normal.
AB  - Women are living longer after a cancer diagnosis because of advances in early
      detection and treatment. However, although our ability to effectively treat
      gynecologic malignancies has improved, survivors of gynecologic cancer often face
      profound physical, emotional, sexual, and psychosocial challenges as a result of
      their cancer diagnosis and treatment. In this article, we discuss how patient
      comorbidities (i.e., obesity) and cancer treatment effects may adversely affect
      sexual health outcomes, gastrointestinal function, and general health among
      survivors of gynecologic cancer. The importance of a multidisciplinary, patient
      centered approach to survivorship care is emphasized. 

PMID- 24857116
TI  - Value considerations in the treatment of head and neck cancer: radiation,
      chemotherapy, and supportive care.
AB  - The management of head and neck cancer has advanced in many areas, including but
      not limited to diagnostic imaging and response assessment, radiation delivery,
      surgical approaches, combined-modality therapy, as well as new drug discovery.
      These advances have become widely used, however, the associated improvements in
      outcomes of interest compared with other options may at times be modest in
      magnitude or supported by limited data. In addition, the price tag of these
      advancements is often high. There is a growing mandate to look at existing data
      to identify insights into how to improve the value of care and to better
      understand the comparative effectiveness of one intervention versus another with
      regard to tumor control, quality of life, and other important outcomes; such
      insights become particularly important when considerable disparities exist in
      related costs. We review selected issues in radiotherapy, chemotherapy and
      supportive care applicable to the management of head and neck cancer and relevant
      to ascertaining the value of care. 

PMID- 24857117
TI  - A value framework in head and neck cancer care.
AB  - The care of head and neck squamous cell carcinoma has greatly evolved over the
      past 30 years. From single modality to a multidisciplinary care, there has also
      been a concurrent increase in treatment intensity, resulting, at many times, in
      more zealous regimens that patients must endure. In this article, we apply
      Porter's value model as a framework to balance survival, toxicities, cost, and
      trade-offs from a patient's perspective in head and neck cancer. This model
      defines value as the health outcome per dollar achieved. Domains and outcomes
      that are important to patients, including not only survival or short-term quality
      of life, but also functional outcomes, recovery, sustainability of recovery, and
      the lasting consequences of therapy are included in this framework. Other
      outcomes that are seldom measured in head and neck cancer, such as work
      disability and financial toxicities, are also included and further discussed.
      Within this value model and based on evidence, we further discuss de-escalation
      of care, intensity-modulated radiation therapy, newer surgical methods, and
      enhancements in the process of care as potential approaches to add value for
      patients. Finally, we argue that knowing the patient's preferences is essential
      in the value discussion, as the attribute that will ultimately provide the most
      value to the individual patient with head and neck cancer. 

PMID- 24857118
TI  - Global response to the burden of cancer: the WHO approach.
AB  - As the burden of many cancer types of major public health relevance worldwide are
      in part determined by behavioral risks, much of the success of cancer control
      depends on the up take of prevention strategies at the population level. Over the
      last decade, the World Health Organization (WHO) has developed global prevention
      strategies of major relevance for cancer prevention and the prevention of other
      non-communicable diseases (NCDs), such as the 2003 WHO Framework Convention on
      Tobacco Control and others. The implementation of these core strategies gained
      momentum in 2011, when heads of states at the United Nation's (UN) High Level
      Meeting (HLM) on NCDs declared that NCDs are a global health threat that menaces
      social and economic development globally and requires urgent action. They asked
      for a paradigm change of the global health agenda by including NCD prevention and
      control into the group of priorities set by the Millennium Development Goals.
      WHO's translation of this call for action by the UN into practice has been
      consolidated into one clearly defined the WHO Global NCD Action Plan 2013-2020,
      including the pre-existing prevention strategies. Although cancer risk reduction
      will profit from the WHO Global NCD Action Plan, comprehensive cancer prevention
      and control will require other supplementary strategies not included in the plan
      because they are not shared with other NCDs. Causality of the over 200 cancer
      types is complex. A myriad of non-behavioral factors such as environmental and
      infectious risks, require specific attention when planning comprehensive cancer
      prevention. In reducing the cancer burden globally much will depend on how
      prevention strategies are implemented and how progress in cancer treatment can be
      translated into the reality of health systems in less affluent countries. 

PMID- 24857119
TI  - Novel treatments for chronic lymphocytic leukemia and moving forward.
AB  - The last several years have seen an explosion of novel therapies for chronic
      lymphocytic leukemia (CLL). These include the antibody obintutuzumab (GA-101), as
      well as small-molecule inhibitors of key pathways involved in the pathogenesis of
      CLL, specifically the B-cell receptor (BCR) pathway (especially Bruton's tyrosine
      kinase [BTK] and P13K), and the antiapoptotic pathway (especially BCL-2). We will
      consider each in turn, focusing on the molecules most advanced in clinical
      development. There has also been extensive development in rewiring the patient's
      own immune system to treat CLL. This has been done through modifying autologous T
      cells to express a chimeric antigen receptor (CAR). Thus far all CAR-T
      preparations have targeted the CD19 antigen. This is a good rational for B-cell
      malignancies as CD19 expression is limited to B-cell malignancies and normal B
      cells. The in vivo amplification of the transduced T cells relies on signaling
      and co-signaling domains and provides significant killing of CLL cells. As
      exciting as these novel agents and approaches are, they obviously beg the
      question, will chemotherapy as a treatment for CLL soon be obsolete? Although
      chemotherapy is associated with known short-term toxicities, it has the advantage
      of being completed in a short period of time and being relatively inexpensive in
      comparison to novel therapies. In addition, long-term follow-up of results with
      chemoimmunotherapy have now identified a group of patients whose remissions are
      maintained for more than 10 years. An important question that will arise going
      forward is how to incorporate novel agents without eliminating the long term
      benefits possible with chemoimmunotherapy in a subset of patients with CLL. 

PMID- 24857120
TI  - Should triple-negative breast cancer (TNBC) subtype affect local-regional therapy
      decision making?
AB  - The more aggressive biologic characteristics and the current lack of targeted
      therapy for triple-negative breast cancer (TNBC) make local-regional management
      decisions challenging for physicians. TNBC is associated with patients of younger
      age, black race and BRCA1 mutation carriers. Distinctions between BRCA1
      associated and sporadic TNBC include increased lifetime risk of ipsilateral and
      contralateral breast cancer after breast cancer therapy (BCT) for BRCA carriers,
      which is not shared by sporadic TNBC. However, the presence of a BRCA mutation
      should not preclude a breast-conservation approach in patients who are otherwise
      appropriate candidates for BCT. Data suggest that local-regional relapse (LRR) at
      baseline after BCT appears to be comparable for TNBC and the HER2-positive
      subgroups, but is about 50% greater than luminal tumors. LRR appears to be
      similarly increased after mastectomy; thus, TNBC should not be a contra
      indication for BCT. Recent hypothesis-generating data suggest less LRR after BCT
      (where radiation is routinely delivered) than with mastectomy for early-stage
      TNBC. To date, no specific local-regional guideline recommendations for TNBC
      exist. Level I outcome data for TNBC using accelerated partial breast irradiation
      (APBI) and hypofractionated whole-breast irradiation (hWBRT) are lacking. TNBC
      should be treated with APBI only on clinical trials. Although hWBRT may be
      considered in TNBC, its association with younger age, advanced disease and use of
      systemic chemotherapy often precludes its use for this subtype. Until definitive
      treatment strategies are validated in large datasets and confirmed in randomized
      trials, TNBC subtype, in and of itself, should not direct local-regional
      management treatment decisions. 

PMID- 24857121
TI  - Indications for allogeneic hematopoietic cell transplantation for acute myeloid
      leukemia in the genomic era.
AB  - Few choices in medical oncology are as stark as the decision of whether or not to
      proceed with allogeneic hematopoietic cell transplantation (HCT) in the treatment
      of acute myeloid leukemia (AML). Recent advances provide more information to
      inform the decision, including molecular studies of leukemia that predict tumor
      responsiveness, assays of minimal residual disease that measure early treatment
      outcome, and comorbidity indices that predict nonrelapse mortality. Although
      large prospective studies incorporating all of these factors are lacking,
      literature reviews and consensus statements exist that can help the clinician in
      this difficult choice. Allogeneic HCT should be considered for all patients
      younger than age 65, with an available donor, an acceptable comorbidity index,
      and whose had initial induction therapy has failed. Similarly, allogeneic HCT is
      appropriate therapy for all patients with AML in second remission younger than
      age 75, with an appropriate donor, and a comorbidity index of 5 or less. For
      patients younger than age 60 with AML in first complete remission (CR), there is
      little evidence that HCT benefits those with favorable-risk disease who achieve
      CR with one cycle of induction and have no evidence of minimal residual disease.
      Allogeneic HCT is indicated for essentially all other categories of patients. For
      those age 60 and older, few prospective studies are available on which to base
      recommendations, but, as in younger patients, the benefit of allogeneic HCT is
      questionable for patients with favorable-risk AML. For patients with higher-risk
      disease, allogeneic HCT is a reasonable option with the caution that the risk of
      HCT increases dramatically in those with a comorbidity index of 3 or higher. 

PMID- 24857122
TI  - New molecular abnormalities and clonal architecture in AML: from reciprocal
      translocations to whole-genome sequencing.
AB  - Acute myeloid leukemia (AML) is characterized by recurrent genetic alterations,
      including amplifications, deletions, rearrangements, and point mutations.
      Clinically, these lesions can be used to stratify patients into categories of
      risk, which directs further clinical management and prognostication. Patient risk
      categories were first described based on recurrent karyotypic abnormalities; most
      patients with AML, however, fall into intermediate cytogenetic risk, the majority
      harboring a normal karyotype. Subsequently, identification of recurrently mutated
      genes, including FLT3, NPM1, and CEBPA, allowed further stratification of
      patients with a normal karyotype. More extensive genomic and epigenomic analysis
      of AML samples has expanded the number of known molecular alterations present in
      this disease. The further understanding of this mutational landscape has shed
      light into the pathogenesis of AML. AML arises in a founding clone that often
      gives rise to subclones. Clonal evolution is a feature of the natural history of
      the disease but may also be influenced by the selective pressure of chemotherapy.
      The complex network of genetic and epigenetic alterations in this disease has
      yielded numerous new targets for intervention. In the future, further
      understanding of this mutational framework, along with the development of novel
      therapeutic targets, may lead to improved outcomes for patients with AML. 

PMID- 24857123
TI  - Novel therapies in AML: reason for hope or just hype?
AB  - We have entered the genomic sequencing era in the treatment of acute myeloid
      leukemia (AML); our patients increasingly and justifiably demand personalized
      treatment based on aberrations of their own leukemia. Except in rare cases we are
      not yet able to provide truly personalized therapy, so the question of "hope or
      hype?" posed by the American Society for Clinical Oncology (ASCO) for this
      educational topic is quite timely. The answer based solely on advances in genomic
      sequencing is "both". There is an element of expectation among the public that we
      are "almost there" in solving the genetic cancer puzzle, an expectation indeed
      based on hype. However, there is no question that ultimate success lies in
      understanding the genetic underpinnings of disease. When decades of research in
      molecular biology and immunology are combined with transformative advances in
      cancer genetics, the answer is undeniably that our patients finally have reason
      for hope. Here, we review selected novel therapies for AML in areas such as
      immunotherapeutics, epigenetics, kinase inhibition/pathway inhibition, and the
      marrow microenvironment. 

PMID- 24857124
TI  - Management and future directions in non-small cell lung cancer with known
      activating mutations.
AB  - Lung cancer accounts for a quarter of all cancer deaths. Non-small cell lung
      cancer (NSCLC) is currently segregated by the presence of actionable driver
      oncogenes. This review will provide an overview of molecular subsets of lung
      cancer, including descriptions of the defining oncogenes (EGFR, ALK, KRAS, ROS1,
      RET, BRAF, ERBB2, NTRK1, FGFR, among others) and how these predict for response
      to small molecule tyrosine kinase inhibitors (TKIs) that are either clinically
      available or in clinical trial development for advanced NSCLC. Particular focus
      will be placed on subsets with EGFR mutated and ALK rearranged NSCLC. Somatic TKI
      sensitizing EGFR mutations (such as exon 19 deletions and L858R substitutions)
      are the most robust predictive biomarker for symptom improvement, radiographic
      response, and increment in progression-free survival (PFS) when EGFR TKIs
      (gefitinib, erlotinib, and afatinib) are used for patients with advanced NSCLC.
      However, the palliative benefits that EGFR TKIs afford are limited by multiple
      biologic mechanisms of tumor adaptation/resistance (such as the EGFR-T790M
      mutation and oncogene bypass tracks), and future efforts toward delaying,
      preventing, and treating resistance are underway. Similar to EGFR mutations, ALK
      rearrangements exemplify an oncogene-driven NSCLC that can be effectively
      palliated with a precision TKI therapy (the multitargeted ALK/MET/ROS1 TKI
      crizotinib). When resistance to first-line crizotinib therapy occurs, multiple
      second generation ALK TKIs have demonstrated impressive rates of disease control
      in clinical trials, and these may modify long-term outcomes for patients with ALK
      positive NSCLC. The development of TKIs for other oncogene-driven NSCLCs may
      expand the portfolio of precision therapies for this recalcitrant cancer. 

PMID- 24857125
TI  - Systemic treatment of advanced thymic malignancies.
AB  - The rarity of thymic malignancies prevents us from performing large randomized
      clinical trials. As a result, systemic treatment decisions are often guided by a
      small amount of prospective trial data, retrospective series, and individual case
      reports. In recent years, we have begun to unravel the molecular biology of
      thymic tumors. It is becoming more apparent as a result of gene expression
      profiling and genomic clustering studies that the subclassifications of type A,
      AB, B1, B2, B3, and thymic carcinoma have different molecular features that may
      be clinically relevant. Genomic profiling distinguishes type B3 thymoma and
      thymic carcinoma as distinct entities from type A and type B2 thymoma.
      Furthermore, type B2 thymomas can be separated from other subgroups in that it
      has a more distinct lymphocytic component than the other groups where epithelial
      cells predominate. Next generation RNA sequencing has recently identified a large
      microRNA cluster on chromosome 19q13.42 in types A and AB thymomas, which is
      absent in type B thymomas and thymic carcinomas. This cluster has been shown to
      result in activation of the phosphoinositide 3-kinase (PI3K)/AKT pathway, which
      suggests a possible role for PI3K inhibitors in these subtypes. The presence of
      KIT mutations in thymic carcinomas is also well described. Herein we discuss the
      chemotherapeutic and targeted treatment options for advanced thymic malignancies
      and highlight important advances in our understanding of the molecular biology of
      these rare tumors. 

PMID- 24857126
TI  - Optimizing chemotherapy in triple-negative breast cancer: the role of platinum.
AB  - Although characterization of triple-negative breast cancer (TNBC) using mRNA gene
      expression profiling has certainly provided important insights, the concept of
      targeting DNA repair defects with DNA damaging therapeutics such as platinum in
      TNBC has been advanced from studies focusing on both germline and somatic genetic
      alterations associated with this breast cancer subtype. A growing body of
      preclinical and clinical data suggests that platinum chemotherapy has a potential
      role to play in the treatment of both early-stage and advanced TNBC, though
      results are not yet definitive. Randomized clinical trials that incorporate
      biomarkers of response, including germline BRCA1 and BRCA2 mutation status as
      well as tumor-based measures of genomic "scarring" resulting from the
      accumulation of DNA damage in tumors with deficient repair capacity, will help to
      clarify the optimal use and activity of platinum in TNBC. 

PMID- 24857127
TI  - Chemotherapy for lung cancers: here to stay.
AB  - Four decades of clinical research document the effectiveness of chemotherapy in
      patients with lung cancers. Chemotherapeutic agents can improve lung cancer
      symptoms, lengthen life in most patients with lung cancers, and enhance
      curability in individuals with locoregional disease when combined with surgery or
      irradiation. Chemotherapy's effectiveness is enhanced in patients with EGFR
      mutant and ALK-positive lung cancers and can "rescue" individuals whose oncogene
      driven cancers have become resistant to targeted agents. As immunotherapies
      become part of the therapeutic armamentarium for lung cancers, chemotherapeutic
      drugs have the potential to modulate the immune system to enhance the
      effectiveness of immune check point inhibitors. Even in this era of personalized
      medicine and targeted therapies, chemotherapeutic agents remain essential
      components in cancer care. 

PMID- 24857128
TI  - Novel formulations and new mechanisms of delivering chemotherapy.
AB  - The identification of epidermal growth factor receptor mutations and anaplastic
      lymphoma kinase rearrangements and the development of targeted therapy for
      patients with these molecular alterations has been a tremendous advance in the
      treatment of advanced stage or metastatic non-small cell lung cancer (NSCLC).
      However, the majority of patients with advanced stage NSCLC will not have one of
      these molecular alterations and will receive chemotherapy as their primary
      therapy. Chemotherapy remains a critical component of therapy for resected and
      locally advanced NSCLC, as well as for patients with limited-stage and extensive
      stage small cell lung cancer (SCLC). A significant unmet need exists to develop
      novel chemotherapy agents and to improve the efficacy and toxicity of currently
      available agents. Several novel formulations of currently available chemotherapy
      agents are in development for NSCLC and SCLC. Antibody conjugates are therapeutic
      agents that employ a tumor-specific monoclonal antibody conjugated to a cytotoxic
      or radionuclide agent. After the monoclonal antibody binds to the tumor antigen,
      these agents are internalized, and the link between the antibody and the
      therapeutic agent is dissolved and the cytotoxic agent is release
      intracellularly. This enhanced delivery of chemotherapy to malignant tissues has
      the potential to improve efficacy and reduce toxicity. Antibody conjugates to
      therapeutic agents are currently available for other malignancies and are in
      development for NSCLC and SCLC. 

PMID- 24857129
TI  - Surveillance imaging for lymphoma: pros and cons.
AB  - There is no international consensus on the optimal frequency or duration of
      computed tomography or positron emission tomography scanning for surveillance in
      patients who achieve complete remission after initial therapy for lymphoma.
      Although some clinical practice guidelines suggest periodic imaging is
      reasonable, others suggest little or no benefit to this practice. From a
      theoretical perspective, the frequency and duration of surveillance imaging is
      largely dependent upon the lymphoma subtype. Aggressive lymphomas with a fast
      growth rate will require surveillance more frequently and for a shorter duration
      compared to the indolent lymphomas. Historically, relapse has been detected in a
      majority of patients based upon clinically evident signs and symptoms. Currently,
      no study has demonstrated an overall survival difference for patients with
      relapse detected by imaging as opposed to clinical evaluation, although one study
      did demonstrate a lower second-line International Prognostic Index in patients
      with relapse detected by surveillance imaging. Enthusiasm for this finding has
      been tempered by recent studies highlighting the potential long-term risk of
      secondary malignancies because of ionizing radiation exposure from diagnostic
      imaging. These factors along with the significant costs associated with
      diagnostic imaging have contributed to an ongoing debate regarding the relative
      costs, risks, and benefits of radiographic surveillance. Herein we present
      perspectives for and against routine surveillance imaging in an effort to
      facilitate a better understanding of the issues relevant to what is ultimately a
      clinical decision made by an oncologist and his or her patient. 

PMID- 24857131
TI  - Update on the biology and clinical management of Merkel cell carcinoma.
AB  - Merkel cell carcinoma (MCC) is a rare but aggressive neuroendocrine cutaneous
      malignancy, with a predilection for sun-exposed sites in elderly patients.
      Despite an incidence 30 times less than that of melanoma, its disease-specific
      mortality is three times higher. Management of MCC remains challenging because of
      a limited understanding of its molecular biology, lack of prospective clinical
      trials, and limitations associated with retrospective reviews of therapeutic
      options. With the recent discovery of an associated human polyomavirus,
      significant progress has been made in the understanding of the pathogenesis of
      this malignancy. With this progress, there has been increasing optimism regarding
      new tools in the therapeutic armamentarium to fight this deadly disease. Here we
      present an overview on MCC with an emphasis on the most recent biologic
      discoveries and the rationale for novel targeted and immunotherapies. 

PMID- 24857130
TI  - Developments in the treatment of locally advanced and metastatic squamous cell
      carcinoma of the skin: a rising unmet need.
AB  - Squamous cell carcinoma of the skin (SCCS) is a common malignancy with
      potentially devastating consequences in patients with locally advanced or
      metastatic disease. Its rising incidence, primarily a result of an aging
      population and increased ultraviolet (UV) radiation exposure, characterize an
      emerging unmet need. A firm understanding of the biology of this disease, likely
      distinct from that of other squamous malignancies because of the influence of UV
      radiation, is necessary in the evaluation of treatment paradigms. Careful
      recognition of high-risk features pertaining to tumor and host characteristics is
      paramount to proper management. However, a lack of standardization in guidelines
      in this regard creates a challenge for physicians. Questions persist regarding
      additional evaluation and treatment for advanced disease such as the roles for
      sentinel lymph node biopsy and the adjuvant use of radiation and chemotherapy.
      With respect to advanced disease, multiple combinations of chemotherapy have been
      tested with variable success, but no rigorous randomized studies have been
      conducted. In addition, EGFR inhibitors such as cetuximab and erlotinib have
      displayed antitumor activity and as such, warrant further investigation. In sum,
      the treatment of locally advanced and metastatic SCCS is a ripe area for clinical
      investigation. This article summarizes the current understanding of disease
      biology and emerging questions in the management of this disease. 

PMID- 24857132
TI  - Frontline approach to metastatic BRAF-mutant melanoma diagnosis, molecular
      evaluation, and treatment choice.
AB  - An estimated 76,100 patients will be diagnosed with invasive melanoma in the
      United States in 2014, and 9,710 patients will die from the disease. In almost
      all cases, the cause of death is related to the development of widespread
      metastatic disease. Although death rates from most types of cancer have steadily
      decreased in the United States--a 20% decrease during two decades from a peak of
      215.1 deaths per 100,000 population in 1991 to 171.8 in 2010--death rates from
      melanoma have steadily increased during the same time, especially among males.
      The news regarding melanoma is far from all bad. Increases in our understanding
      of the human immune system have led to the development of new immunotherapeutic
      drugs such as ipilimumab, which has been shown to improve survival in phase III
      trials in metastatic melanoma, and anti-programmed death 1 (anti-PD1) antibodies,
      recently hailed by ASCO as one of the past year's most noteworthy clinical cancer
      advances. However, no discovery has influenced and, indeed, transformed the
      management of metastatic melanoma more than the identification of activating
      mutations in the BRAF gene in the mitogen-activated protein kinase (MAPK)
      pathway, which occur in about half of cutaneous melanomas and can be targeted
      with small molecule inhibitors of the BRAF protein, the downstream MEK protein,
      or both. This article will address how patients with metastatic melanoma are
      evaluated for their mutation status and how the presence of a targetable mutation
      influences therapeutic decisions regarding systemic therapy and even surgery.

PMID- 24857133
TI  - Accelerated aging among cancer survivors: from pediatrics to geriatrics.
AB  - There are almost 14-million cancer survivors in the United States and the
      population is growing. Almost two-thirds of these survivors are age 65 or older.
      Given this, it is imperative to understand the impact of cancer and its therapies
      on the aging process. Childhood cancer survivors, diagnosed with cancer at age 21
      or younger, particularly females, have rates of frailty similar to rates in older
      adults. This phenomenon appears to start early, suggesting an aging phenotype.
      Frailty among childhood cancer survivors increases risk for chronic disease and
      mortality. Adults diagnosed with cancer are faced with the effects of cancer and
      its therapies compounded by the issues of multiple morbidities that occur with
      the typical aging process. Intervention studies to date have focused on smoking
      cessation, diet, and exercise, as well as improving rates of late effects
      surveillance in childhood cancer survivors. No intervention studies have
      specifically addressed the issue of frailty or multiple morbidities in cancer
      survivors. Concerted efforts must continue to create and disseminate survivorship
      care plans to all cancer survivors. 

PMID- 24857134
TI  - Pediatric melanoma: the whole (genome) story.
AB  - Pediatric melanoma is rare and given the diagnostic challenges it presents in
      this age group, it is difficult to interpret the literature describing its
      natural history and outcome. Recent genomic analysis demonstrates that
      conventional melanoma in children and adolescents shares many of the genomic
      features that have been described in adult melanoma, including BRAF mutations.
      Thus, this patient group should be given the opportunity to enroll in National
      Cancer Institute and pharmaceutically sponsored trials that incorporate novel
      targeted agents. 

PMID- 24857135
TI  - Targeting BRAF in pediatric brain tumors.
AB  - The role of BRAF in adult malignancy has been well documented over the last
      decade and recent data have extended these findings to a number of pediatric
      cancers. In this and the accompanying articles, we will review the importance of
      the BRAF pathway in signal transduction resulting in cell proliferation,
      migration, differentiation, and angiogenesis with a focus on three major
      pediatric diseases: brain tumors, Langerhans cell histiocytosis (LCH), and
      melanoma. Mutated BRAF proteins are being identified in an increasing number of
      pediatric cancers and the development of drugs that can target these mutant
      proteins offers enormous therapeutic opportunity for these diseases. Because of
      variations in the types of mutations of BRAF observed in different tumors,
      particularly those of the central nervous system, an understanding of the
      feedback loops that regulate monomeric and dimeric BRAF signaling will be
      critical in selecting the optimal targeted inhibitors. The two most commonly
      observed alterations in BRAF in patients with brain tumor are the BRAF V600E
      point mutation and the KIAA1549 truncated fusion and targeting of these will need
      to differ to account for these feedback loops. Many other factors will influence
      the activity of novel agents in BRAF activated tumors, including their ability to
      penetrate the blood-brain barrier (for brain tumors and some patients with LCH)
      as well as the development of drug resistance and toxicity profiles. Well
      controlled trials that take these variables into consideration are already
      underway and highlight the need for molecular classification of pediatric central
      nervous system tumors. 

PMID- 24857136
TI  - Predisposition to pediatric and hematologic cancers: a moving target.
AB  - Our understanding of hereditary cancer syndromes in children, adolescents, and
      young adults continues to grow. In addition, we now recognize the wide variation
      in tumor spectrum found within each specific cancer predisposition syndrome
      including the risk for hematologic malignancies. An increased understanding of
      the genetic mutations, biologic consequences, tumor risk, and clinical management
      of these syndromes will improve patient outcome. In this article, we illustrate
      the diversity of molecular mechanisms by which these disorders develop in both
      children and adults with a focus on Li-Fraumeni syndrome, hereditary
      paraganglioma syndrome, DICER1 syndrome, and multiple endocrine neoplasia
      syndrome. This is followed by a detailed discussion of adult-onset tumors that
      can occur in the pediatric population including basal cell carcinoma, colorectal
      cancer, medullary thyroid cancer, and adrenal cortical carcinoma, and the
      underlying hereditary cancer syndromes that these tumors could indicate. Finally,
      the topic of leukemia predisposition syndromes is explored with a specific focus
      on the different categories of syndromes associated with leukemia risk (genetic
      instability/DNA repair syndromes, cell cycle/differentiation, bone marrow failure
      syndromes, telomere maintenance, immunodeficiency syndromes, and transcription
      factors/pure familial leukemia syndromes). Throughout this article, special
      attention is made to clinical recognition of these syndromes, genetic testing,
      and management with early tumor surveillance and screening. 

PMID- 24857137
TI  - Biological and therapeutic implications of the BRAF pathway in histiocytic
      disorders.
AB  - Langerhans cell histiocytosis (LCH) has historically evolved in its
      classification from a primary immune dysregulatory disorder to what current
      evidence supports as a dendritic cell neoplasm with an immune-inflammatory
      component. A key part of the classification of LCH as a neoplasm has been the
      identification of BRAF V600E mutations in 35% to 60% of cases. Tumor protein p53
      (TP53) and RAS mutations have also been identified, albeit in less than 2% of
      reported cases. Of note, over 50% of patients with another dendritic cell
      disease, Erdheim-Chester Disease, have also been shown to have BRAF V600E
      mutations. Although the BRAF mutations have not been shown to be associated with
      extent of disease, they may still provide a target for a molecularly guided
      approach to therapy. In cases of LCH in which no BRAF mutations were identified,
      there was evidence for activation of the RAS-RAF-MEK-extracellular signal
      regulated kinases (ERK) pathway, suggesting that similar to other tumors, this
      pathway may be therapeutically exploitable. Anecdotal responses have been
      reported in a few patients with LCH and Erdheim-Chester Disease to vemurafenib, a
      BRAF V600E inhibitor. Although these results pave the way for careful,
      prospective clinical testing, selection of the optimal groups in which to test
      such inhibitors, alone or in combination, will be critical based on the toxicity
      profile thus far observed in adults with melanoma and other BRAF mutated tumors. 

PMID- 24857138
TI  - Community oncology in an era of payment reform.
AB  - Patients and payers (government and private) are frustrated with the fee-for
      service system (FFS) of payment for outpatient health services. FFS rewards
      volume and highly valued services, including expensive diagnostics and
      therapeutics, over lesser valued cognitive services. Proposed payment schemes
      would incent collaboration and coordination of care among providers and reward
      quality. In oncology, new payment schemes must address the high costs of all
      services, particularly drugs, while preserving the robust distribution of sites
      of service available to patients in the United States. Information technology and
      personalized cancer care are changing the practice of oncology. Twenty-first
      century oncology will require increasing cognitive work and shared decision
      making, both of which are not well regarded in the FFS model. A high proportion
      of health care dollars are consumed in the final months of life. Effective
      delivery of palliative and end-of-life care must be addressed by practice and by
      new models of payment. Value-based reimbursement schemes will require oncology
      practices to change how they are structured. Lessons drawn from the principles of
      primary care's Patient Centered Medical Home (PCMH) will help oncology practice
      to prepare for new schemes. PCMH principles place a premium on proactively
      addressing toxicities of therapies, coordinating care with other providers, and
      engaging patients in shared decision making, supporting the ideal of value
      defined in the triple aim-to measurably improve patient experience and quality of
      care at less cost. Payment reform will be disruptive to all. Oncology must be
      engaged in policy discussions and guide rational shifts in priorities defined by
      new payment models. 

PMID- 24857139
TI  - Compassion, compassion fatigue, and burnout: key insights for oncology
      professionals.
AB  - When cancer care clinicians become stressed, sad, isolated--and unaware of this-
      they are placing themselves at risk for burnout and their patients at risk for
      suboptimal care. Despite their best intentions, clinicians can sink from a
      healthy work state of compassion, empathy, and well-being into compassion fatigue
      and burnout. Lessons from first responders demonstrate the importance for
      clinicians to recognize the warning signs of compassion and fatigue and burnout,
      as this recognition can enable them to take action towards prevention and/or
      recovery. The recognition of these issues as a threat to clinician performance
      has outstripped the development of evidence-based interventions, but
      interventions tested to date are effective, feasible, and scalable. These
      interventions could be incorporated systematically into cancer care.

PMID- 24857140
TI  - Tumor boards: optimizing the structure and improving efficiency of
      multidisciplinary management of patients with cancer worldwide.
AB  - Multidisciplinary management tumor boards are now conducted worldwide for the
      management of patients with cancer. Studies evaluating their influence on
      decision making and patient outcome are limited; however, single-center studies
      have reported significant changes in diagnosis and treatment plans. A survey from
      Arabic countries showed widespread use and reliance on tumor boards for decision
      making. A recent multi-institutional survey of veteran affairs (VA) hospitals in
      the United States found limited association between the presence of tumor boards
      and care and outcomes. The Cancer Care Outcomes Research and Surveillance
      Consortium looked at the association between tumor board features and measures of
      quality of care. Results of overall survival among the patients of these
      physicians participating in tumor boards is ongoing, but preliminary results are
      outlined along with a recent ASCO survey of international members on the
      presence, utilization, and influence of tumor boards in this article. Tumor
      boards allow for implementation of clinical practice guidelines and may help
      capture cases for clinical trials. Efforts to improve preparations, structure,
      and conduct of tumor boards, research methods to monitor their performance,
      teamwork, and outcomes are outlined also in this article. The concept of mini
      tumor boards and more efficient methods for MDM in countries with limited
      resources are also discussed. In suboptimal settings, such as small community
      hospitals, rural areas, and areas with limited resources, boundaries in diagnosis
      and management can be overcome, or at least improved, with tumor boards,
      especially with the use of video-conferencing facilities. Studies from the United
      Kingdom showed that special training of multidisciplinary teams (MDT) led to
      better team dynamics and communication, improved patient satisfaction, and
      improved clinical outcome. The weight of the benefits versus the time and effort
      spent to improve efficiency, patient care, and better time management in the
      United States and in the international oncology community is also reviewed in
      this article. 

PMID- 24857141
TI  - The effect of accountable care organizations on oncology practice.
AB  - Cancer care accounts for a significant portion of the rise in health care costs,
      and therefore, as national efforts escalate to control cost, cancer care will be
      a focus of concern. Cost increases in cancer care are related to many factors,
      including increasing cancer incidence in an aging population, the introduction of
      new high-cost therapeutics, and the high cost of end-of-life care. Accountable
      care organizations (ACOs) have been one of the major efforts directed at
      controlling health care costs. How cancer care will fit into the rubric of ACOs
      is not entirely clear but will certainly evolve over the coming years. The
      oncology profession has the opportunity to play a role in this evolution or could
      leave the evolution to others driving the process, such as the Centers for
      Medicare and Medicaid Services (CMS), private payers, and ACOs. Ideally all
      parties will work together to provide a construct for high-value, high-quality
      care for patients with cancer while contributing to cost control in overall
      health care. 

PMID- 24857142
TI  - Achieving a deeper understanding of the implemented provisions of the Affordable
      Care Act.
AB  - The Patient Protection and Affordable Care Act (ACA) was signed into law by
      President Barack Obama on March 23, 2010. Since that time, numerous regulations
      have been promulgated, legal battles continue to be fought and the major
      provisions of the law are being implemented. In the following article, we outline
      components of the ACA that are relevant to cancer health care, review current
      implementation of the new health care reform law, and identify challenges that
      may lie ahead in the post-ACA era. Specifically, among the things we explore are
      Medicaid expansion, health insurance exchanges, essential health benefits and
      preventive services, subsidies, access to clinical trials, the Medicare Part D
      donut hole, and physician quality payment reform. 

PMID- 24857143
TI  - Nutritional supplements and cancer: potential benefits and proven harms.
AB  - Nutritional supplements are widely used among patients with cancer who perceive
      them to be anticancer and antitoxicity agents. Large-scale, randomized cancer
      prevention trials have mainly been negative, with some notable adverse and
      beneficial effects. For example, these trials showed that beta-carotene increases
      the risk of lung and stomach cancer, vitamin E increases prostate cancer and
      colorectal adenoma, and selenium reduces gastric and lung cancer in populations
      with low selenium levels but increase rates in those with higher levels. Both
      beta-carotene and vitamin E supplementation increase overall mortality. This
      article reviews phase II and III trials that examine the effects of
      multivitamins, antioxidants, vitamin D, and n-3 supplements on outcome and
      toxicity from cancer treatments. Although vitamin E and beta-carotene reduce
      toxicity from radiotherapy among patients with head and neck cancer, it has been
      found to increase recurrence, especially among smokers. Antioxidants have mixed
      effects on chemotherapy toxicity, but there are no data on outcome. Vitamin D
      deficiency is relatively common among patients with cancer, and ongoing phase III
      trials are studying the effect of vitamin D on outcome as well as optimum vitamin
      D and calcium intakes for bone health. Docosahexanoic and eicosopentanoic acid
      supplements have mixed effects on cachexia and are currently being tested as
      potential adjuncts to maximize response to chemotherapy. Nutritional
      supplementation tailored to an individual's background diet, genetics, tumor
      histology, and treatments may yield benefits in subsets of patients. Clinicians
      should have an open dialogue with patients about nutritional supplements.
      Supplement advice needs to be individualized and come from a credible source, and
      it is best communicated by the physician. 

PMID- 24857144
TI  - Novel treatment targets in sarcoma: more than just the GIST.
AB  - Sarcomas are rare tumors comprising a heterogeneous group of more than 50
      histologic subtypes, the majority of which do not respond well to cytotoxic
      chemotherapy. This has fueled research into the distinct molecular mechanisms of
      tumorigenesis and disease progression for various sarcoma subtypes.
      Gastrointestinal stromal tumors and liposarcomas are presented as paradigms of
      molecular classification that have led to the rational development of novel
      therapeutic strategies for those tumors. Recent advances in understanding of
      growth signaling pathways, metabolic reprogramming, and immune therapy have
      identified new treatment targets for many sarcomas. These investigations will
      form the foundation for further improvements in our ability to care for patients
      with these tumors and may offer clinical insights into a wide range of other
      tumors. 

PMID- 24857145
TI  - Taking on challenging targets: making MYC druggable.
AB  - The transcription factor proto-oncogene c-MYC (hereafter MYC) was first
      identified more than 3 decades ago and has since been found deregulated in a wide
      variety of the most aggressive human malignancies. As a pleiotropic transcription
      factor, MYC directly or indirectly controls expression of hundreds of coding and
      noncoding genes, which affect cell cycle entry, proliferation, differentiation,
      metabolism, and death/survival decisions of normal and cancer cells. Tumors with
      elevated MYC expression often exhibit highly proliferative, aggressive
      phenotypes, and elevated MYC expression has been correlated with diminished
      disease-free survival for a variety of human cancers. The use of MYC
      overexpression or MYC-dependent transcriptional gene signatures as clinical
      biomarkers is currently being investigated. Furthermore, preclinical animal and
      cell-based model systems have been extensively utilized in an effort to uncover
      the mechanisms of MYC-dependent tumorigenesis and tumor maintenance. Despite our
      ever-growing understanding of MYC biology, currently no targeted therapeutic
      strategy is clinically available to treat tumors that have acquired elevated MYC
      expression. This article summarizes the progresses being made to discover and
      implement new therapies to kill MYC over-expressing tumors-a target that was once
      deemed undruggable. 

PMID- 24857146
TI  - The horizon of precision medicine in breast cancer: fragmentation, alliance, or
      reunification?
AB  - Genomic studies have shown that breast cancer includes a large number of
      targetable genomic alterations. Most of these genomic alterations are rare and
      can evolve during the natural history of the disease. Three paths are being
      followed to develop precision medicine in metastatic breast cancer. First, the
      conventional path will consist of fragmenting the disease and developing drugs in
      each rare genomic segment. This will require screening large numbers of patients
      for genomic alterations to run the therapeutic trials, especially the
      registration trials. The second path will consist in clustering rare genomic
      alterations in more frequent segments defined by an altered pathway. Finally, one
      possible path for precision medicine will be to test genomic algorithms for the
      whole patient population with metastatic breast cancer. This latter scenario
      would reunify breast cancer into a single entity and test whether the use of
      genomics would improve outcomes in this population of patients. Challenges and
      perspective in the field of precision medicine will include the prediction of
      resistance, the integration of immunology, and DNA repair in the genomic
      algorithms and the transfer of concepts to early-stage breast cancers. 

PMID- 24857147
TI  - Mass spectrometry-based proteomics: from cancer biology to protein biomarkers,
      drug targets, and clinical applications.
AB  - Proteomics is optimally suited to bridge the gap between genomic information on
      the one hand and biologic functions and disease phenotypes at the other, since it
      studies the expression and/or post-translational modification (especially
      phosphorylation) of proteins--the major cellular players bringing about cellular
      functions--at a global level in biologic specimens. Mass spectrometry technology
      and (bio)informatic tools have matured to the extent that they can provide high
      throughput, comprehensive, and quantitative protein inventories of cells,
      tissues, and biofluids in clinical samples at low level. In this article, we
      focus on next-generation proteomics employing nanoliquid chromatography coupled
      to high-resolution tandem mass spectrometry for in-depth (phospho)protein
      profiling of tumor tissues and (proximal) biofluids, with a focus on studies
      employing clinical material. In addition, we highlight emerging proteogenomic
      approaches for the identification of tumor-specific protein variants, and
      targeted multiplex mass spectrometry strategies for large-scale biomarker
      validation. Below we provide a discussion of recent progress, some research
      highlights, and challenges that remain for clinical translation of proteomic
      discoveries.

PMID- 24857148
TI  - The rising incidence of second cancers: patterns of occurrence and identification
      of risk factors for children and adults.
AB  - As the population of cancer survivors has increased and continues to age, the
      occurrence of second cancers has risen dramatically-from 9% of all cancer
      diagnoses in 1975-1979 to 19% in 2005-2009. The Childhood Cancer Survivor Study,
      a cohort of more than 14,000 childhood cancer survivors with detailed exposure
      data and long-term follow-up, has substantially contributed to our understanding
      of the roles of radiotherapy and chemotherapy in second cancer occurrence. In
      particular, dose-related risks have been demonstrated for second cancers of the
      breast, thyroid, central nervous system, gastrointestinal tract, and sarcomas
      following radiation. Cytotoxic chemotherapy-which has long been known to be
      leukemogenic-also appears to contribute to risk for a range of other second
      cancer types. Individuals who develop a second cancer are at particularly high
      risk for developing additional second cancers. A genome-wide association study of
      survivors of Hodgkin lymphoma who received radiotherapy identified a locus on
      chromosome 6q21 as being associated with second cancer risk, demonstrating that
      recent advances in genomics are likely to prove invaluable for elucidating the
      contribution of genetic susceptibility to second cancer etiology. Among adults,
      risk of second cancers varies substantially by type of first and second cancer,
      patient age, and prevalence of second cancer risk factors, including primary
      cancer treatments, environmental and lifestyle exposures, and genetic
      susceptibility. Further research is needed to quantify second cancer risks
      associated with specific etiologic factors and to identify the patients at
      highest risk of developing a second cancer to target prevention and screening
      efforts. 

PMID- 24857149
TI  - Hype versus hope: metformin and vitamin D as anticancer agents.
AB  - There has been increasing interest in the use of metformin and vitamin D to
      reduce cancer risk and improve outcomes. Metformin, an oral antidiabetic drug,
      improves insulin resistance and has been associated with reduced cancer incidence
      and cancer mortality. Low levels of vitamin D have also been associated with
      increased cancer risk, mainly in retrospective studies, and it has been suggested
      that vitamin D supplementation might play a role in cancer prevention.
      Preclinical data provide a biologic rationale for these associations; however,
      the human data arise predominantly from observational studies and caution is
      needed in their translation into clinical practice. This is because of the
      recognized limitations of observational studies, such as time-related survival
      biases, selection and referral biases, short follow-up, and the presence of
      confounding factors that can lead to spurious or inaccurate findings. Combined
      examination of associations with cancer risk and outcome (occurring when exposure
      in a population that does not yet have cancer is analyzed in relation to cancer
      death) may yield results that are difficult to interpret. Finally, associations
      across all cancers may differ from those in specific cancer types. These
      shortcomings can be overcome in properly designed and adequately powered
      prospective randomized trials; however, such trials are both expensive and time
      consuming. We review the literature examining the associations of metformin and
      vitamin D with cancer, discussing weakness and strengths and making
      recommendations for further research and clinical practice. 

PMID- 24857150
TI  - Prevention of prostate cancer: outcomes of clinical trials and future
      opportunities.
AB  - Prostate cancer is an excellent target for prevention, to reduce both mortality
      and the burden of overdetection of potential inconsequential disease whose
      diagnosis increases cost, morbidity, and anxiety. The Prostate Cancer Prevention
      Trial has demonstrated that finasteride significantly reduces the risk of
      prostate cancer but only low-grade disease; overall survival is unaffected. In
      the Selenium and Vitamin E Cancer Prevention Trial (SELECT) clinical trial,
      selenium had no effect on prostate cancer risk, but alpha tocopherol
      significantly increased the risk by 17%. The most promising future approaches to
      prostate cancer prevention will likely focus on nutrition, especially weight
      control, and through modulation of inflammation. 

PMID- 24857151
TI  - Shedding light on adult medulloblastoma: current management and opportunities for
      advances.
AB  - Few evidence-based guidelines are available for the treatment of adult
      medulloblastoma, an extremely rare disease. Therapeutic regimens, typically
      modeled following pediatric protocols, consist of surgical resection followed by
      radiotherapy with or without adjuvant chemotherapy. Because of the rarity of this
      disease in adults, any treatment undertaken is based mainly on small and
      retrospective studies. Unlike pediatric patients, adults with medulloblastoma
      have been treated according to risk-adapted therapeutic strategies in only a few
      prospective studies. Overall, approximately 30% of patients experience recurrence
      and die of disease-related causes. Although the patients could respond to second
      line treatments, the prognosis of patients with recurrence remains dismal. An
      important challenge for the future will be the biologic characterization of
      medulloblastoma in adults, with the identification of specific genetic patterns
      of patients with different prognosis and different response to targeted
      treatments. 

PMID- 24857152
TI  - Is current technology improving outcomes with radiation therapy for gliomas?
AB  - Radiotherapy (RT) remains the principal component of glioma treatment, and three
      dimensional conformal RT (3DCRT) is the current standard of RT delivery. Advances
      in imaging and in RT technology have enabled more precise treatment to defined
      targets combined with better means of avoiding critical normal structures, and
      this is complemented by intensive quality assurance, which includes on-treatment
      imaging. The refinements of 3DCRT include intensity modulated RT (IMRT), arcing
      IMRT, and high-precision conformal RT, formerly described as "stereotactic,"
      which can be delivered using a linear accelerator or other specialized equipment.
      Although proton therapy uses heavy charged particles, the principal application
      can also be considered as refinement of 3DCRT. The technologies generally improve
      the dose differential between the tumor and normal tissue and enable more dose
      intensive treatments. However, these have not translated into improved survival
      outcome in patients with low- and high-grade gliomas. More intensive altered
      fractionation regimens have also failed to show survival benefit. Nevertheless,
      novel technologies enable better sparing of normal tissue and selective avoidance
      of critical structures, and these need to be explored further to improve the
      quality of life of patients with gliomas. Principal clinical advance in RT has
      been the recognition that less intensive treatments are beneficial for patients
      with adverse prognosis high-grade gliomas. We conclude that the principal gain of
      modern RT technology is more likely to emerge as a reduction in treatment related
      toxicity rather than as an improvement in overall survival; the optimal avoidance
      strategies remain to be defined. 

PMID- 24857153
TI  - For the next trick: new discoveries in radiobiology applied to glioblastoma.
AB  - Glioblastoma (GBM) is the most common malignant brain tumor. Radiotherapy post
      surgical resection remained the mainstay of the management of GBM for decades
      until the addition of temozolomide was shown to prolong the median overall
      survival (OS) by 2.5 months to 14.6 months in 2005. Infiltrative growth to
      surrounding normal brain tissue and cooption of vascular niches, peripheral
      microvasuclar hyperplasia, and central hypoxic regions with pseudopalisading
      necrosis are characteristics of GBM and are causally linked to their exceptional
      radio- and chemo-resistant phenotype. An intratumoral hierarchy is postulated
      consisting of tumor stem cells in the apex with high DNA-repair proficiency
      resisting radiotherapy. It is conceivable that the stem cell property is more
      dynamic than originally anticipated. Niche effects such as exposure to hypoxia
      and intercellular communication in proximities to endothelial or bone marrow
      derived cells (BMDC), for example, may activate such "stem cell" programs. GBM
      are exceptionally stroma-rich tumors and may consist of more than 70% stroma
      components, such as microglia and BMDC. It becomes increasingly apparent that
      treatment of GBM needs to integrate therapies targeting all above-mentioned
      distinct pathophysiological features. Accordingly, recent approaches in GBM
      therapy include inhibition of invasion (e.g., integrin, EGFR, CD95, and mTOR
      inhibition), antiangiogenesis and stroma modulators (TGFbeta, VEGF, angiopoetin,
      cMET inhibitors) and activation of immune response (vaccination and blockage of
      negative co-stimulatory signals). In addition, high LET-radiotherapy, for example
      with carbon ions, is postulated to ablate tumor stem cell and hypoxic cells more
      efficiently as compared with conventional low-LET photon irradiation. We discuss
      current key concepts, their limitations, and potentials to improve the outcome in
      this rapidly progressive and devastating disease. 

PMID- 24857154
TI  - Re: 'predictor factors for mortality in hybrid aortic procedures'.

PMID- 24857155
TI  - Commentary on 'comparison of three contemporary risk scores for mortality
      following elective abdominal aortic aneurysm (AAA) repair'.

PMID- 24857156
TI  - Surgeon still a step behind medicine: indicators of healthcare for peripheral
      artery disease.

PMID- 24857157
TI  - 6-shogaol, a major compound in ginger, induces aryl hydrocarbon receptor-mediated
      transcriptional activity and gene expression.
AB  - Xenobiotics are usually detoxified by drug-metabolizing enzymes and excreted from
      the body. The expression of many of drug-metabolizing enzymes is regulated by the
      aryl hydrocarbon receptor (AHR). Some substances in vegetables have the potential
      to be AHR ligands. To search for vegetable components that exhibit AHR-mediated
      transcriptional activity, we assessed the activity of vegetable extracts and
      identified the active compounds using the previously established stable AHR
      responsive HepG2 cell line. Among the hot water extracts of vegetables, the
      highest activity was found in ginger. The ethyl acetate fraction of the ginger
      hot water extract remarkably induced AHR-mediated transcriptional activity, and
      the major active compound was found to be 6-shogaol. Subsequently, the mRNA
      levels of AHR-targeting drug-metabolizing enzymes (CYP1A1, UGT1A1, and ABCG 2)
      and the protein level of CYP1A1 in HepG2 cells were shown to be increased by 6
      shogaol. This is the first report that 6-shogaol can regulate the expression of
      detoxification enzymes by AHR activation. 

PMID- 24857158
TI  - Acute embryonic or juvenile exposure to Deepwater Horizon crude oil impairs the
      swimming performance of mahi-mahi (Coryphaena hippurus).
AB  - The Deepwater Horizon incident likely resulted in exposure of commercially and
      ecologically important fish species to crude oil during the sensitive early life
      stages. We show that brief exposure of a water-accommodated fraction of oil from
      the spill to mahi-mahi as juveniles, or as embryos/larvae that were then raised
      for ~25 days to juveniles, reduces their swimming performance. These
      physiological deficits, likely attributable to polycyclic aromatic hydrocarbons
      (PAHs), occurred at environmentally realistic exposure concentrations.
      Specifically, a 48 h exposure of 1.2 +/- 0.6 MUg L(-1) SigmaPAHs (geometric mean
      +/- SEM) to embryos/larvae that were then raised to juvenile stage or a 24 h
      exposure of 30 +/- 7 MUg L(-1) SigmaPAHs (geometric mean +/- SEM) directly to
      juveniles resulted in 37% and 22% decreases in critical swimming velocities
      (Ucrit), respectively. Oil-exposed larvae from the 48 h exposure showed a 4.5
      fold increase in the incidence of pericardial and yolk sac edema relative to
      controls. However, this larval cardiotoxicity did not manifest in a reduced
      aerobic scope in the surviving juveniles. Instead, respirometric analyses point
      to a reduction in swimming efficiency as a potential alternative or contributing
      mechanism for the observed decreases in Ucrit. 

PMID- 24857159
TI  - Comparison of soft-tissue orbital morphometry in attractive and normal Italian
      subjects.
AB  - OBJECTIVE: To identify esthetic characteristics of the orbital soft tissues of
      attractive Italian adult women and men. MATERIALS AND METHODS: Three-dimensional
      computerized digitizers were used to collect the coordinates of facial landmarks
      in 199 healthy, normal subjects aged 18 to 30 years (71 women, 128 men; mean age,
      22 years) and in 126 coetaneous attractive subjects (92 women, 34 men; mean age,
      20 years) selected during beauty competitions. From the landmarks, six linear
      distances, two ratios, six angles, and two areas were calculated. Attractive
      subjects were compared with normal ones by computing z-scores. RESULTS:
      Intercanthal width was reduced while eye fissure lengths were increased in both
      genders. Orbital heights (os-or) were increased only in attractive women, with a
      significant gender-related difference. The inclinations of the eye fissure were
      increased in attractive subjects, while the inclinations of the orbit were
      reduced. For several of the analyzed measurements, similar patterns of z-scores
      were observed for attractive men and women (r  =  .883). CONCLUSION: Attractive
      women and men had several specific esthetic characteristics in their orbital soft
      tissues; esthetic reference values can be used to determine optimal goals in
      surgical treatment.

PMID- 24857163
TI  - Fracture toughness and cyclic fatigue resistance of resin composites with
      different filler size distributions.
AB  - OBJECTIVES: To verify the influence of filler size distributions on fracture
      toughness (KIc), initial fracture strength (IFS) and cyclic fatigue resistance
      (CFR) of experimental resin composites. METHODS: Four composites were prepared
      with same inorganic content (78 wt%), in which 67 wt% was constituted by glass
      particles with d50 of 0.5; 0.9; 1.2; 1.9 MUm KIc of the composites was determined
      by the single-edge notched beam (SENB) method. To evaluate the IFS and the CFR a
      biaxial bending test configuration was used. The CFR was determined under cyclic
      loading for 10(5) cycles using the 'staircase' approach. The fracture surfaces of
      IFS and CFR specimens were analyzed under scanning electron microscope (SEM).
      RESULTS: There was a positive linear correlation between d50 vs. KIc and
      statistical difference was found only between C0.5 (1.24+/-0.10 MPa m0.5) and
      C1.9 (1.41+/-0.17 MPa m0.5). There were no statistical differences among IFS
      means, which ranged from 155.4+/-18.8 MPa (C0.9) to 170.7+/-23.1 MPa (C1.2). C0.5
      (93.0+/-18.6a MPa) showed the highest and C0.9 the lowest CFR (82.5+/-8.0c MPa).
      There was no correlation between CFR with d50 values or with KIc means. SEM
      images showed the morphology with brittle fracture patterns for the surfaces of
      IFS specimens and a more smooth fracture surface for CFR specimens. SIGNIFICANCE:
      Resin composites showed different failure mechanisms for quasi-static and fatigue
      loading. For KIc and IFS, composites with larger filler size distributions showed
      better results due to crack deflection; while under cyclic loading, viscous
      behavior was predominant and composites with smaller particles showed higher
      fatigue resistance.

PMID- 24857164
TI  - Initial identification & selection bias versus the eventual confirmation of
      talent: evidence for the benefits of a rocky road?
AB  - The relative age effect (RAE), whereby earlier birthdate children within a
      selection year are more commonly selected as talented, has been highlighted in
      the literature. As a consequence, these young athletes get into specialised
      training earlier and in greater numbers, leading (it is suggested) to a
      disproportionate opportunity for success. However, this disproportionality seems
      not to be manifest in senior teams. Accordingly, we examine the identification
      and conversion rates for academy rugby players, examining a sample of all players
      passing into and either graduating, or being dismissed from, a major English
      rugby academy. Data demonstrated a reversal of the RAE "benefit", whereby late
      birth players were less likely to be selected, but more likely to achieve senior
      professional status. Possible reasons are explored and, on the basis of our data,
      we propose a psychologically based explanation of greater "growth" due to
      additional challenge experienced by these initially disadvantaged younger
      players.

PMID- 24857165
TI  - Assessment of fetal lung maturity by ultrasound: objective study using gray-scale
      histogram.
AB  - OBJECTIVE: To evaluate lung maturity using ultrasound (US), comparing the
      subjective and gray-scale histogram (GSH) techniques. METHODS: A total of 77
      single pregnancies were evaluated and divided into the following two groups: 11
      women of gestational age 28 to 35 + 6 weeks and 66 women >= 36 weeks. The women
      underwent to emergency or planned cesarean section, according to fetal-maternal
      indications. The US was performed on the mean sagittal plane of the fetal torso,
      in order to observe the lung and hepatic areas. Fetal lung maturity was evaluated
      subjectively and through GSH. After delivery, the incidence of respiratory
      distress in the newborn was evaluated. The analyses were considered to be correct
      or incorrect, and comparisons were made using the McNemar test. In order to
      compare lung/hepatic echogenicity using GSH in groups with and without
      respiratory distress, the Student's t-test was used. RESULTS: The subjective
      evaluation identified 41 cases (53.2%) correctly and 36 (46.8%) incorrectly,
      while GSH found 58 (75.3%) correctly and 19 (24.7%) incorrectly (p = 0.006).
      There was a significant difference in mean lung/hepatic echogenicity between the
      groups with and without respiratory distress (1.05 versus 1.26; p = 0.002). In
      the group of 28 to 35 + 6 weeks, GSH presented sensitivity, specificity and
      accuracy in predicting respiratory distress of 61.9%, 89.1% and 81.6%,
      respectively. CONCLUSION: The evaluation of fetal lung maturity through GSH was
      more effective than the subjective method in predicting respiratory distress
      among newborns.

PMID- 24857166
TI  - Schmallenberg virus circulation in high mountain ecosystem, Spain.

PMID- 24857167
TI  - Is the critical point for aperture crossing adapted to the person-plus-object
      system?
AB  - When passing through apertures, individuals scale their actions to their shoulder
      width and rotate their shoulders or avoid apertures that are deemed too small for
      straight passage. Carrying objects wider than the body produces a person-plus
      object system that individuals must account for in order to pass through
      apertures safely. The present study aimed to determine whether individuals scale
      their critical point to the widest horizontal dimension (shoulder or object
      width). Two responses emerged: Fast adapters adapted to the person-plus-object
      system by maintaining a consistent critical point regardless of whether the
      object was carried while slow adapters initially increased their critical point
      (overestimated) before adapting back to their original critical point. The
      results suggest that individuals can account for increases in body width by
      scaling actions to the size of the object width but people adapt at different
      rates.

PMID- 24857168
TI  - Evaluation of the total MBL confirm kit (ROSCO) for detection of metallo-beta
      lactamases in Pseudomonas aeruginosa and Acinetobacter baumannii.
AB  - Phenotypic tests for carbapenemase production in Pseudomonas aeruginosa and
      Acinetobacter baumannii have been associated with unspecific metallo-beta
      lactamase (MBL) inhibitor activity in synergy tests and low positive predictive
      value. In this study, a collection of well-characterized P. aeruginosa and A.
      baumannii isolates was used to evaluate the inhibitor-based Total MBL Confirm Kit
      and the MBL Etest. 

PMID- 24857169
TI  - Utility of inflammatory markers in predicting the aetiology of pneumonia in
      children.
AB  - We aimed to investigate the diagnostic value of applying cut-off levels of
      inflammatory markers and to develop a prediction model for differentiation
      between bacterial and viral infections in paediatric community-acquired pneumonia
      based on C-reactive protein (CRP), neutrophil, and white cell counts (WCC).
      Amongst 401 children, those with bacterial pneumonia were older than those with
      viral pneumonia (P<0.001). Compared to viral, bacterial infections had a higher
      median CRP level (P<0.001), whereas WCC and neutrophil count were not different.
      Bacterial infections were associated with higher CRP >80 mg/L than viral
      infections (P=0.001), but levels <20 mg/L were not discriminatory (P=0.254).
      Receiver operating characteristic curve of the model for differentiating
      bacterial from viral pneumonia based on age, CRP, and neutrophil count produced
      area under the curve of 0.894 with 75.7% sensitivity and 89.4% specificity. This
      aetiological discriminant prediction model is a potentially useful tool in
      clinical management and epidemiological studies of paediatric pneumonia. 

PMID- 24857170
TI  - Delineation of the molecular basis of borderline hemoglobin A2 in Chinese
      individuals.
AB  - BACKGROUND: The "gray zone" of borderline hemoglobin A2 (Hb A2) may be present in
      a large section of the population, especially in countries where thalassemia is
      common. However, very little is currently known of the molecular basis of
      borderline Hb A2 in Chinese individuals. METHOD: In this study, we performed a
      comprehensive analysis of the globin genotypes and KLF1 gene mutations associated
      with borderline Hb A2 in 165 Chinese subjects. RESULT: Fifteen (9.1%) were
      positive for a molecular defect in the alpha-,beta-globin genes, of whom, alpha
      thalassemia mutations and alpha-globin gene triplication were found in eleven
      cases, accounting for about 73.3% of these globin gene defects. Twenty (12.1%)
      were positive for a molecular defect in the KLF1 gene. Eight different mutations
      were identified, six of which are here reported for the first time. The most
      common is the G176AfsX179 mutation, accounting for 50% of the total. CONCLUSIONS:
      The molecular characterization of borderline Hb A2 in Chinese individuals is
      significantly different than in Italian population. Our data is conductive to
      provision of genetic counseling for Chinese individuals with borderline Hb A2.

PMID- 24857171
TI  - Serial assessment of laser Doppler flow during acute pain crises in sickle cell
      disease.
AB  - Changes in basal laser Doppler flowmetry (LDF) of skin blood flow in sickle cell
      disease are reported to have pathophysiologic relevance in pain crisis. This is
      the first study to strictly control for LDF variability in determining the value
      of serial, basal (unprovoked) skin LDF as a practical method to assess resolution
      of acute pain crisis in sickle cell patients. Daily LDF measurements were
      repeated on the exact same skin areas of the calf and forehead throughout each of
      12 hospital admissions for uncomplicated acute pain crisis. A progressive
      increase in perfusion was observed in the calf throughout hospitalization as pain
      crisis resolved, but measurement reproducibility in the calf was poor.
      Reproducibility in the forehead was better, but no significant trend over time in
      perfusion was seen. There was no significant correlation between perfusion and
      pain scores over time. There was also no significant pattern of LDF oscillations
      over time. In conclusion, only perfusion units and not oscillatory patterns of
      LDF have probable pathophysiological significance in sickle cell disease vaso
      occlusion. The reproducibility of basal skin LDF specifically in sickle cell
      disease needs to be confirmed. 

PMID- 24857172
TI  - MALAT1 promotes cell proliferation in gastric cancer by recruiting SF2/ASF.
AB  - The functions of long non-coding RNAs (lncRNAs) in gastric cancer (GC) remain
      largely unknown. MALAT1 is a kind of lncRNA that had been validated as a pivotal
      metastasis and prognosis mark in lung adenocarcinoma. In this study, we found
      that MALAT1 was aberrantly highly expressed in GC cell lines (SGC-7901, MKN-45
      and SUN-16), and induced specific distribution and over-expression of SF2/ASF in
      nucleolus. Knock-down of MALAT1 or SF2/ASF in SGC-7901 cells respectively induced
      significant arrest of cell cycle in G0/G1 phase along with a remarkable
      suppression of cell proliferation, and the nuclear distribution and expression of
      SF2/ASF was significantly impaired when MALAT1 was depleted. However, over
      expression of SF2/ASF exhibited no effect on rescuing the cell proliferation
      suppression by MALAT1 depletion. These results suggest that MALAT1 may function
      as a promoter of GC cell proliferation partly by regulating SF2/ASF, and our
      findings may provide us a likely biomarker and a potential target for GC
      diagnosis and therapeutic treatment. 

PMID- 24857173
TI  - Health conditions for travellers to Saudi Arabia for the Umra and pilgrimage to
      Mecca (Hajj) - 2014.

PMID- 24857174
TI  - Improving the quality of tuberculosis care: we need standards and strategies to
      translate them into practice.

PMID- 24857175
TI  - Assessment of knowledge, attitudes and practices regarding tuberculosis among
      final year students in Yazd, Central Iran.
AB  - Tuberculosis (TB) remains a global health problem. Treatment and prevention of TB
      has shifted from inpatient to outpatient settings. A report from the World Health
      Organization has emphasized educational strategy to ensure students graduate with
      the appropriate knowledge, skills, and attitudes essential to the effective
      management of TB. The objective of this study was to determine the level of
      knowledge, attitudes and practices among medical students. The survey was done
      from 2012 to 2013. Knowledge, attitudes and practices were assessed regarding
      tuberculosis with a questionnaire. Knowledge mean score of students was 16.13+/
      2.06 and Attitude score was 36.08+/-3.76, Knowledge and attitude levels of
      students were moderate to high in the majority of them. Practice score of the
      study subjects was 22.77+/-4.95, 11.9% of students had poor practice level. 43%
      did not know that a sputum smear is the most important method used for diagnosis
      of TB. Two-thirds of them did not know the distance that should be kept from
      contagious patients. Half of them believed that the BCG vaccination has no role
      in the prevention of TB. This study concluded that more efforts should be made to
      improve the knowledge of students regarding TB transmission and the role of
      sputum smear in diagnosis. The importance of the BCG vaccination should be
      emphasized. 

PMID- 24857176
TI  - Egyptian students' guardians knowledge, attitude and predictors of negative
      attitude of epilepsy in Assiut city.
AB  - BACKGROUND: Epilepsy is very prevalent in Egypt, approaching 6.98 per 1000
      population. This study was designed to assess the knowledge and attitudes towards
      epilepsy among guardians of Egyptian high school students. METHODS: A cross
      sectional study was made among guardians (parents/guardians) of high school
      students in Assiut city, Egypt. A 15-item questionnaire was self-administered by
      1257 students' guardians who were randomly selected. RESULTS: All recruited
      parents/guardians of high school students had heard about epilepsy. Families with
      a patient with epilepsy (PWE) had significantly better information about epilepsy
      and its aetiology than other families. The predictors of negative attitudes
      towards PWE were: age group ranging from 40 to 49years, no work, skilled work,
      male sex and incorrect knowledge. CONCLUSION: Having a patient with epilepsy is a
      predictor to having greater knowledge and a better attitude towards epilepsy.
      However, people still have a concept that PWE are stigmatized and are different
      from others. Raising awareness about epilepsy and its aetiology will increase the
      knowledge and improve the attitudes towards PWE.

PMID- 24857177
TI  - Difference in cerebral blood flow velocity in neonates with and without
      hyperbilirubinemia.
AB  - PURPOSE: To evaluate the difference in cerebral blood flow velocity (CBFV) in
      neonates with and without hyperbilirubinemia. METHODS: CBFV of 70 healthy late
      preterm and term newborns with unconjugated hyperbilirubinemia (UCH) reaching the
      threshold of phototherapy requirement was compared with 70 gestational- and
      postnatal age-matched controls without hyperbilirubinemia. Resistance index (RI),
      pulsatility index (PI), peak systolic velocity (PSV) and vascular diameter were
      measured in internal carotid, vertebral and middle cerebral arteries by
      transcranial color Doppler ultrasound at the beginning of phototherapy, after 48
      72h of starting phototherapy and at 5-7days after its stoppage. In controls CBFV
      was assessed once at inclusion. RESULTS: Both the groups were comparable. An
      increase in CBFV (decreased RI and PI, increased PSV and vasodilation) was
      observed in the UCH group. A further increase in CBFV was noticed after 48h of
      phototherapy. After 5-7days of stoppage of phototherapy, though there was a
      significant reduction in CBFV in mild-to-moderate UCH (serum bilirubin ?25mg/dL),
      in severe UCH (serum bilirubin >25mg/dL), CBFV remained increased. Four neonates
      developed features of acute bilirubin encephalopathy and had significantly higher
      CBFV compared to those with normal outcome. CONCLUSIONS: An increase in CBFV was
      observed in neonates with UCH compared to those without hyperbilirubinemia.

PMID- 24857178
TI  - Effects of habitat characteristics on the growth of carrier population leading to
      increased spread of typhoid fever: a model.
AB  - In this paper, a non-linear model is proposed and analyzed to study the effects
      of habitat characteristics favoring logistically growing carrier population
      leading to increased spread of typhoid fever. It is assumed that the cumulative
      density of habitat characteristics and the density of carrier population are
      governed by logistic models; the growth rate of the former increases as the
      density of human population increases. The model is analyzed by stability theory
      of differential equations and computer simulation. The analysis shows that as the
      density of the infective carrier population increases due to habitat
      characteristics, the spread of typhoid fever increases in comparison with the
      case without such factors. 

PMID- 24857179
TI  - The global cancer divide: relationships between national healthcare resources and
      cancer outcomes in high-income vs. middle- and low-income countries.
AB  - BACKGROUND: Cancer continues to rise as a contributor to premature death in the
      developing world. Despite this, little is known about whether cancer outcomes are
      related to a country's income level, and what aspects of national healthcare
      systems are associated with improved cancer outcomes. METHODS: The most recent
      estimates of cancer incidence and mortality were used to calculate mortality-to
      incidence ratio (MIR) for the 85 countries with reliable data. Countries were
      categorized according to high-income (Gross Domestic Product (GDP)>$15,000) or
      middle/low-income (GDP<$15,000), and a multivariate linear regression model was
      used to determine the association between healthcare system indicators and cancer
      MIR. Indicators study included per capita GDP, overall total healthcare
      expenditure (THE), THE as a proportion of GDP, total external beam radiotherapy
      devices (TEBD) per capita, physician density, and the year 2000 WHO healthcare
      system rankings. RESULTS: Cancer MIR in high-income countries (0.47) was
      significantly lower than that of middle/low-income countries (0.64), with a
      p<0.001. In high-income countries, GDP, health expenditure and TEBD showed
      significant inverse correlations with overall cancer MIR. A $3040 increase in GDP
      (p=0.004), a $379 increase in THE (p<0.001), or an increase of 0.59 TEBD per
      100,000 population (p=0.027) were all associated with a 0.01 decrease in cancer
      MIR. In middle/low-income countries, only WHO scores correlated with decreased
      cancer MIR (p=0.022); 12 specific cancer types also showed similar significant
      correlations (p<0.05) as overall cancer MIR. CONCLUSIONS: The analysis of this
      study suggested that cancer MIR is greater in middle/low-income countries.
      Furthermore, the WHO healthcare score was associated with improved cancer
      outcomes in middle/low-income countries while absolute levels of financial
      resources and infrastructure played a more important role in high-income
      countries.

PMID- 24857180
TI  - Final program evaluation methods and results of a National Lymphedema Management
      Program in Togo, West Africa.
AB  - In order to eliminate Lymphatic Filariasis (LF) as a public health problem, the
      World Health Assembly recommends an approach which includes interruption of
      transmission of infection and the alleviation of morbidity. In 2000, the Togolese
      National Program to Eliminate Lymphatic Filariasis (PNELF) started the annual
      mass drug administrations and in 2007, the program added a morbidity component
      for the management of lymphedema. This manuscript describes the methods of an
      evaluation aimed at assessing the strengths and weaknesses of the Togolese
      National Lymphedema Morbidity Program. The evaluation was conducted through in
      depth interviews with stakeholders at each programmatic level. Interviews focused
      on message dissemination, health provider training, patient self-care practices,
      social dynamics, and program impact. The evaluation demonstrated that the program
      strengths include the standardization and in-depth training of health staff,
      dissemination of the program's treatment message, a positive change in the
      community's perception of lymphedema, and successful patient recruitment and
      training in care techniques. The lessons learned from this evaluation helped to
      improve Togo's program, but may also provide guidance and strategies for other
      countries desiring to develop a morbidity program. The methods of program
      evaluation described in this paper can serve as a model for monitoring components
      of other decentralized national health programs in low resource settings. 

PMID- 24857181
TI  - Nosocomial pathogens associated with the mobile phones of healthcare workers in a
      hospital in Anyigba, Kogi state, Nigeria.
AB  - BACKGROUND: Mobile phones of healthcare workers (HCWs) could be colonized by
      potential bacteria pathogens. The aim of this research is to evaluate the
      bacterial contamination and antibiotic sensitivity pattern of isolates from
      mobile phones of HCWs in Grimad hospital. METHOD: A total of 112 swab samples
      were collected from the mobile phones of HCWs and students in June 2012 in
      Anyigba. While 56 samples were from HCWs in Grimad hospital, 56 samples were
      obtained from non-healthcare workers (NHCWs) who served as the control. The
      samples were all screened for bacterial pathogens by standard bacteriological
      procedures. Antibiotic susceptibility testing was done by the disc diffusion
      technique. RESULTS: The rate of bacterial contamination of mobile phones of HCWs
      was 94.6%. Bacteria isolated from mobile phones of HCWs were more resistant to
      antibiotics than NHCWs phones. Staphylococcus Epidermidis (42.9%) was the most
      frequently isolated bacteria followed by Bacillus spp. (32.1%), Staphylococcus
      Aureus (25%), Pseudomonas Aeruginosa (19.6%), Escherichia Coli (14.3%),
      Streptococcus spp. (14.3%), Proteus spp. (12.5%), Klebsiella spp. (7.1%), and
      Acinetobacter spp. (5.3%). Cotrimoxazole, ampicillin and tetracycline showed high
      levels of resistance while gentamicin, ciprofloxacin and ceftriaxone exhibited
      encouraging results. CONCLUSION: The presence of bacteria pathogens associated
      with nosocomial infection was identified. Transmission of pathogens can be
      reduced by hand hygiene and regular cleaning of mobile phones.

PMID- 24857182
TI  - Health problems and the health care provider choices: a comparative study of
      urban and rural households in Egypt.
AB  - OBJECTIVE: To assess families' health problems and the health facility choices in
      an urban and a rural district in Egypt. METHODS: A cross-sectional descriptive
      study with a multi-stage random sample of 948 urban and 401 rural households was
      undertaken in a district of Cairo and rural Giza. Data was collected through
      interviews. The questionnaire addressed health problems and the use of health
      services within the fortnight prior to the survey. A follow-up of a sub-sample of
      285 urban and 114 rural households was carried out 2-3weeks after the first
      interview to assess the outcome of complaints. The EPi Info Statistical Package
      was used for analysis and comparing urban and rural families. RESULTS: Over 60%
      of urban and 78.8% of rural families had health complaints - respiratory,
      gastrointestinal and musculoskeletal. Outpatient clinics in public hospitals were
      the first choice for 49.7% of urban families and 23% of rural, while 25.7% of
      urban and 42.8% of rural families visited private clinics. Over half of the
      families with complaints recover from their illnesses within a fortnight.
      CONCLUSION: Urban families have less health complaints than rural; however, rural
      families recover sooner. Families bypass often public primary health care
      services. Urban families overuse outpatient clinics in public hospitals.

PMID- 24857183
TI  - The role of inflammation in cancer of the esophagus.
AB  - Esophageal adenocarcinoma is the eighth most common malignancy worldwide. The
      overall prognosis is poor, with 5-year survival ranges of approximately 15-25%,
      and 30-50% for patients who can be treated with curative intent. There has been a
      marked increase in incidence of esophageal adenocarcinoma over the last 30 years,
      with chronic and severe reflux, diet and obesity identified as principal factors
      fuelling this rise in the West. Esophageal adenocarcinoma is an exemplar model of
      an inflammation-associated cancer. The key molecular pathways driving tumor
      development and influencing tumor biology are the subject of considerable
      research efforts, and is the principal focus of this review. In addition, the
      diverse range of changes occurring in the local immune response, tissue
      microenvironment, metabolic profile, intracellular signaling mechanisms and
      microRNA signatures are discussed, as well as novel targeted therapies. 

PMID- 24857184
TI  - Precordial electrode placement for optimal ECG monitoring: implications for
      ambulatory monitor devices and event recorders.
AB  - INTRODUCTION: Detection of QRS complexes, P-waves and atrial fibrillation f-waves
      in electrocardiographic (ECG) signals is critical for the correct diagnosis of
      arrhythmias. We aimed to find the best bipolar lead (BL) with the highest signal
      amplitude and shortest inter-electrode spacing. METHODS: ECG signals (120
      seconds) were recorded in 36 patients with 16 precordial electrodes placed in a
      standardized pattern. An average signal was analysed for each of 120 possible BLs
      obtained by calculating the difference between pairs of unipolar leads. Peak-to
      peak amplitudes of QRS waves (50ms around R-peak) and P waves (270-70ms before R
      peak) were calculated. For patients with atrial fibrillation, power of the
      fibrillatory (f) wave was used instead. Maximum values at each distance were
      considered and differentiation analysis was performed based on incremental
      changes (amplitude to distance). RESULTS: There was a significant correlation
      between distance and QRS-amplitude (r=0.78, p<0.001), P-wave amplitude (r=0.60,
      p<0.01) and f-wave power (r=0.79, p<0.001). The range of values was: QRS
      amplitude 0.7-2.33mV, P-wave amplitude 0.07-0.18mV, and f-wave power 0.55
      2.12mV(2)/s. The maximum value for the shortest distance was on a heart-aligned
      axis over the left ventricle for the QRS complex (1.9mV at 8.7cm) and over the
      atria for the P-wave (0.98mV) and f-waves (1.45mV(2)/s at 8cm, respectively).
      CONCLUSION: There is a strong positive correlation between electrode distance and
      ECG signal-amplitude. Distance of 8cm on a heart-aligned axis and over the
      relevant heart-chamber provides the highest signal amplitude for the shortest
      distance. These findings are essential for the design and use of ambulatory
      monitoring devices.

PMID- 24857185
TI  - "In their perception we are addicts": social vulnerabilities and sources of
      support for men released from drug treatment centers in Vietnam.
AB  - BACKGROUND: Amid the global transition to treat opioid addiction as an illness,
      many people who inject drugs (PWID) face heterogeneous legal environments that
      include both punitive and harm reduction measures. In Vietnam, many PWID, who
      have a high burden of HIV, are sent to drug treatment centers, or "06 centers",
      for compulsory detoxification, vocational training, and labor for up to four
      years. This study investigates the challenges and facilitators of reentry into
      community and family life among men who are released from "06 centers" and
      provides insights and recommendations for developing policies and interventions
      that address special needs of this vulnerable population. METHODS: In-depth
      interviews were conducted in 2011 by trained interviewers among a sample of 43
      male PWID released within the past 2 years from "06 centers" in Hanoi, Vietnam to
      investigate the above issues and to recommend potential interventions.
      Participants were recruited from outpatient HIV clinics that serve PWID (n=22)
      and through peer referral from self-help groups for PWID (n=21). Interviews were
      audiotaped, transcribed, translated, entered into Atlas.TI qualitative data
      analysis software and analyzed for key themes. RESULTS: The interviews revealed
      persistent drug-related stigmatization, frequently paired with HIV-related
      stigmatization and discrimination, which hindered employment, increased
      participants' social isolation and exacerbated their struggles with addiction.
      Families were participants' primary source of financial, employment, and
      emotional support, but addiction-related family tensions also had negative
      psychological effects. Participants identified methadone maintenance treatment as
      an effective means of overcoming addiction, yet few could fully benefit from this
      treatment due to its limited availability. CONCLUSION: Our study suggests that
      PWID released from "06 centers" would greatly benefit from the scale-up of
      community-based harm reduction measures that include addiction and HIV treatment,
      coupled with employment-support and family centered mental health services.

PMID- 24857186
TI  - Two-photon neuronal and astrocytic stimulation with azobenzene-based
      photoswitches.
AB  - Synthetic photochromic compounds can be designed to control a variety of proteins
      and their biochemical functions in living cells, but the high spatiotemporal
      precision and tissue penetration of two-photon stimulation have never been
      investigated in these molecules. Here we demonstrate two-photon excitation of
      azobenzene-based protein switches and versatile strategies to enhance their
      photochemical responses. This enables new applications to control the activation
      of neurons and astrocytes with cellular and subcellular resolution. 

PMID- 24857187
TI  - A graphene-based biosensing platform based on the release of DNA probes and
      rolling circle amplification.
AB  - We report a versatile biosensing platform capable of achieving ultrasensitive
      detection of both small-molecule and macromolecular targets. The system features
      three components: reduced graphene oxide for its ability to adsorb single
      stranded DNA molecules nonspecifically, DNA aptamers for their ability to bind
      reduced graphene oxide but undergo target-induced conformational changes that
      facilitate their release from the reduced graphene oxide surface, and rolling
      circle amplification (RCA) for its ability to amplify a primer-template
      recognition event into repetitive sequence units that can be easily detected. The
      key to the design is the tagging of a short primer to an aptamer sequence, which
      results in a small DNA probe that allows for both effective probe adsorption onto
      the reduced graphene oxide surface to mask the primer domain in the absence of
      the target, as well as efficient probe release in the presence of the target to
      make the primer available for template binding and RCA. We also made an
      observation that the circular template, which on its own does not cause a
      detectable level of probe release from the reduced graphene oxide, augments
      target-induced probe release. The synergistic release of DNA probes is
      interpreted to be a contributing factor for the high detection sensitivity. The
      broad utility of the platform is illustrated though engineering three different
      sensors that are capable of achieving ultrasensitive detection of a protein
      target, a DNA sequence and a small-molecule analyte. We envision that the
      approach described herein will find useful applications in the biological,
      medical, and environmental fields. 

PMID- 24857189
TI  - Plasma fibrinogen level on admission to the intensive care unit is a powerful
      predictor of postoperative bleeding after cardiac surgery with cardiopulmonary
      bypass.
AB  - INTRODUCTION: Evidence regarding the behavior of fibrinogen levels and the
      relation between fibrinogen levels and postoperative bleeding is limited in
      cardiac surgery under cardiopulmonary bypass (CPB). To evaluate perioperative
      fibrinogen levels as a predictor of postoperative bleeding in patients undergoing
      cardiac surgery with CPB. MATERIALS AND METHODS: In this prospective, single
      center, observational cohort study of 1956 patients following cardiac surgery
      with CPB, fibrinogen level was measured perioperatively. Excessive bleeding group
      was defined as patients with a 24-h chest tube output (CTO) exceeded the 90th
      percentile of distribution. RESULTS: The median 24-h CTO was 728.6+/-431.1ml. A
      total of 189 patients (9.7%) were identified as having excessive bleeding. At
      admission to the intensive care (Day 0), the fibrinogen levels were 2.5+/-0.8g/l
      and 2.1+/-0.8g/l in the control and excessive bleeding groups, respectively
      (P<0.0001). The fibrinogen level on Day 0 was significantly correlated with the
      24-h CTO (rho=-0.237; P<0.0001). Multivariate analysis demonstrated that the
      fibrinogen level at Day 0 was the best perioperative standard laboratory test to
      predict excessive bleeding (P=0.0001; odds ratio, 0.5), whereas preoperative
      fibrinogen level was not a predictor. Using receiver operating characteristics
      curve analyses, the best Day 0 fibrinogen level cutoff to predict postoperative
      bleeding was 2.2g/l. CONCLUSIONS: In this large prospective study, the fibrinogen
      level upon admission to the intensive care unit after CPB predicted the risk of
      postoperative bleeding. Our data add to the concern regarding the fibrinogen
      level threshold that might require fibrinogen concentrate infusion to reduce
      postoperative blood loss.

PMID- 24857190
TI  - Effect of intensive glycemic control on platelet reactivity in patients with long
      standing uncontrolled diabetes.
AB  - BACKGROUND: It has been previously shown that platelets of patients with diabetes
      are more reactive and less responsive to anti-platelet drugs compared with
      platelets from subjects without diabetes. Studies examining the effect of
      glycemic control on platelet reactivity have yielded conflicting data. Thus, in
      this study, we sought to explore the effect of tight glycemic control on platelet
      reactivity in patients with long standing uncontrolled diabetes. METHODS: The
      study included 30 patients with long-standing treated diabetes and a baseline
      HbA1c level of >= 8.5%. All patients were treated with aspirin and statins.
      Patients were tested at baseline and after 3 months of intensive glycemic and
      metabolic control. The treatment goal was to achieve a HbA1c level of <= 7%.
      Platelet reactivity was assessed by light transmission aggregation in response to
      5 and 10 MUM ADP and to 0.5mg/ml arachidonic acid (AA). Additonally, platelet
      activation was assessed by plasma levels of soluble P-selectin using an enzyme
      linked immunosorbent assay. RESULTS: The mean duration of diabetes from the time
      of diagnosis was 20.46 +/- 9.31 years. Baseline HbA1c was 9.4 +/- 0.8%. Following
      the intensive glycemic control period, the HbA1C level decreased to 8.1 +/- 0.8%
      (P < 0.0001). Other laboratory parameters did not change significantly except for
      triglyceride levels, which decreased. None of the platelet aggregation studies
      nor P-selectin levels differed between baseline and after 3 months of intensive
      glycemic control. CONCLUSIONS: Intensive glycemic control in patients with
      longstanding uncontrolled diabetes does not seem to result in a reduction in
      platelet reactivity.

PMID- 24857191
TI  - Urticaria and bacterial infections.
AB  - The association between urticaria and infectious diseases has been discussed for
      >100 years. However, a causal relationship with underlying or precipitating
      infection is difficult to establish. The purpose of this work was to perform a
      systematic analysis of the published cases of urticaria associated with bacterial
      infections. We give an umbrella breakdown of up-to-date systematic reviews and
      other important publications on the complex association of urticaria and
      bacterial infections. We did a Medline search, for English language articles
      published until January 2014, using the key words "urticaria" and
      "bacteria/bacterial disease"; a second analysis was performed in groups of
      bacteria and using each germ name as a key word. Many bacterial infections have
      been associated with urticaria manifestation, such as Helicobacter pylori,
      Streptococcus, Staphylococcus, Mycoplasma pneumonia, Salmonella, Brucella,
      Mycobacterium leprae, Borrelia, Chlamydia pneumonia, and Yersinia enterocolitica.
      In some cases the skin manifestations, described as urticaria, could be caused by
      the presence of the microorganism in the skin, or for the action of their toxins,
      or to the complement activation mediated by circulating immune complexes.
      Although only a weak association with urticaria of unclear pathogenesis exists,
      clinicians should consider these bacterial agents in the workup of the patients
      with urticaria. The eradication of the infection could, in fact, lead to the
      resolution of urticaria. Prospective studies and well-structured research are
      obviously needed to better clarify the real role of bacteria in the pathogenesis
      of urticaria and their relative prevalence.

PMID- 24857194
TI  - Response: the overlooked endometrial injury underlying hysteroscopy procedures.

PMID- 24857195
TI  - Response: hysteroscopy prior to a first IVF treatment cycle: the need for well
      performed RCT.

PMID- 24857197
TI  - Bone metabolism and adipokines: are there perspectives for bone diseases drug
      discovery?
AB  - INTRODUCTION: Over the past 20 years, the idea that white adipose tissue (WAT) is
      simply an energy depot organ has been radically changed. Indeed, present
      understanding suggests WAT to be an endocrine organ capable of producing and
      secreting a wide variety of proteins termed adipokines. These adipokines appear
      to be relevant factors involved in a number of different functions, including
      metabolism, immune response, inflammation and bone metabolism. AREAS COVERED: In
      this review, the authors focus on the effects of several adipose tissue-derived
      factors in bone pathophysiology. They also consider how the modification of the
      adipokine network could potentially lead to promising treatment options for bone
      diseases. EXPERT OPINION: There are currently substantial developments being made
      in the understanding of the interplay between bone metabolism and the metabolic
      system. These insights could potentially lead to the development of new treatment
      strategies and interventions with the aim of successful outcomes in many people
      affected by bone disorders. Specifically, future research should look into the
      intimate mechanisms regulating peripheral and central activity of adipokines as
      it has potential for novel drug discovery.

PMID- 24857201
TI  - The effect of solids retention times on the characterization of extracellular
      polymeric substances and soluble microbial products in a submerged membrane
      bioreactor.
AB  - In this study, the effect of solids retention times (SRTs) on extracellular
      polymeric substances (EPS) and soluble microbial products (SMPs) were
      investigated in a membrane bioreactor (MBR) at SRTs of 10, 5 and 3 days. The
      results showed that more carbohydrates and proteins were accumulated at short
      SRT, which can due to the higher biomass activity in the reactor. The molecular
      weight (MW) distribution analysis suggested that macromolecules (MW>30 kDa) and
      small molecules (MW<1 kDa) were the dominant fraction of EPS and SMP,
      respectively. The reactor at shorter SRT had more small molecules and less
      macromolecules of carbohydrates. The MW distribution of total organic carbon
      (TOC) suggested that other organic moieties were exuded by microbes into the
      solution. The shorter SRT had more undefined microbial by-product-like substances
      and different O - H bonds in hydroxyl functional groups.

PMID- 24857202
TI  - A second duodenal biopsy is necessary in the follow-up of adult coeliac patients.
AB  - INTRODUCTION: Coeliac disease is a chronic enteropathy requiring a close follow
      up. However, the best way to follow up coeliac patients has not yet been
      established. In the last 14 years, we have been offering patients a thorough
      series of periodical examinations including a histological re-evaluation at 12-18
      months. PATIENTS AND METHODS: The notes of all coeliac patients attending our
      clinic between September 1999 and March 2013 were examined. RESULTS: Data from
      317 adult patients were collected. Duodenal biopsy showed a lack of satisfactory
      histological response in 25/317 patients; endomysial antibodies were still
      positive in 76, and diet adherence and clinical response were unsatisfactory in
      58 and 97, respectively. Correlations of serological data, clinical response, and
      diet adherence with histological findings were evaluated. Although the P values
      showed statistically significant differences, sensitivity and specificity were
      disappointing: 64% and 80% for serological response, 48% and 71% for clinical
      response, 56% and 85% for diet adherence. CONCLUSIONS: After 12-18 months on a
      gluten-free diet, 8% of the patients do not present a satisfactory histological
      response; only some of them could have been identified with a serological and/or
      clinical re-evaluation. Therefore, a duodenal biopsy seems to be the only tool
      that could identify patients with unsatisfactory histological response.

PMID- 24857203
TI  - Cardiovascular calcification violet pearl.

PMID- 24857204
TI  - [Gene mutations in the diagnosis of MPN and MDS/MPN: current state].

PMID- 24857205
TI  - [Chinese guideline for diagnosis and treatment of acute promyelocytic leukemia
      (2014): shine Chinese characteristic guideline template].

PMID- 24857206
TI  - [Prospective multicentre study of chemotherapeutic regimen containing pirarubicin
      on the treatment of relapsed or refractory acute myeloid leukemia in adults].
AB  - OBJECTIVE: To compare the efficacy and toxicity of the chemotherapeutic regimen
      containing pirarubicin and mitoxantrone on the treatment of relapsed or
      refractory acute myeloid leukemia (AML) in adults. METHODS: In this open
      prospective multicentre study, we randomly assigned patients with relapsed or
      refractory AML to receive TAE regimen (pirarubicin+cytarabine+etoposide) versus
      MAE regimen (mitoxantrone + cytarabine + etoposide). The efficacy and toxicity
      were compared between the two groups. RESULTS: 56 patients entered this clinical
      trial. The complete remission (CR) rate on TAE arm was 79.0% versus 55.6% on MAE
      arm with the overall response (OR) rates of 86.8% versus 88.9%, respectively. The
      CR was higher on TAE arm (P=0.035) but with no significant difference between the
      two groups regarding the overall response (OR) rate. The regimens were well
      tolerated in both groups. Hematologic and non-hematologic toxicity were similar
      except relatively lower the mean dosage of G-CSF, red blood cells and platelets
      transfusion on TAE arm. No significant differences were seen between the two
      groups regarding the overall survival and relapse free survival rates.
      CONCLUSION: TAE regimen might be an effective salvage therapy in patients with
      relapsed or refractory AML.

PMID- 24857207
TI  - [Monosomal karyotype among adult acute myeloid leukemia: clinical characteristic
      and prognostic analysis].
AB  - OBJECTIVE: To explore the clinical characteristics and prognostic value of
      monosomal karyotype (MK) patients in adult acute myeloid leukemia (AML). METHODS:
      We retrospectively studied 45 patients of MK+ in newly-diagnosed adult AML in our
      center from Oct 2000 to Dec 2012. Clinical characteristics, cytogenetic data and
      prognostic features were analyzed in the cohort of MK+ patients. RESULTS: MK was
      found in 45 patients (19.0%) of 237 newly-diagnosed adult AML with cytogenetic
      data available at diagnoses. Among these 45 cases, there were 28 male (62.2%) and
      17 female (37.8%). Median age of MK+ patients at diagnose was 58(18-91) years
      old. The presence of -5(31.1%) and -7(17.8%) were the most common chromatid among
      MK+ AML patients. MK was much more prevalent among elderly patients. Among AML
      patients, the proportions of MK+ patients younger than 30, 30 to 59 and older
      than 60 years old groups were 11.5%, 17.7% and 22.4%, respectively. There was no
      difference between MK+ and MK- patients in gender distribution (P=0.545). There
      was also no difference between MK+ and MK- patients in the distribution of FAB
      castigation (P=0.239). Median survival of MK+ AML patients was 6.5 months.
      Cumulative 5-year overall survival (OS) of was 5.2%. Forty-three MK+ patients
      (43/45, 95.6%) also had a complex karyotype (CK). Two cases that did not meet the
      CK had not achieved complete remission (CR), and died within 6 months. There were
      12 patients who were CK+ in 192 MK- patients. The differences of OS and CR rates
      between MK+CK+ patients and MK-CK+ were statistically significant (P<0.05).
      CONCLUSION: The increased detection rate of MK with age was associated with lower
      CR and OS in AML patients.

PMID- 24857208
TI  - [Expression level of SET gene in acute myeloid leukemia and its clinical
      significance].
AB  - OBJECTIVE: To investigate the expression level of SET gene in patients with acute
      myeloid leukemia (AML) and evaluate its significance. METHODS: The expression
      level of SET gene in 141 de novo AML patients was determined by real time
      quantitative PCR (RQ-PCR), and its relationship with the clinical features and
      outcomes of these patients were analyzed. RESULTS: SET gene transcript level was
      detected in 141 AML patients with the median expression level of 0.86(range 0.02
      15.69). AML patients with higher SET gene expression had a higher level of white
      blood cell (WBC >= 100 * 109/L) count than of lower SET gene expression ones
      (31.0% vs 11.4%, P=0.005). In the 136 patients who received treatment after
      diagnosis, higher SET gene expression group had lower complete remission rate
      (50.0%) than of lower expression cohort (73.5%) after two cycles of chemotherapy
      (P=0.005). Survival analysis showed that patients with higher SET gene expression
      had significantly shorter overall survival(OS) (10 months vs 22 months, P=0.001)
      and event-free survival (EFS) (2 months vs 14 months, P=0.005) than of lower SET
      gene expression ones. Multivariate COX regression analysis showed SET
      overexpression was an independent prognostic factor for OS. In the patients with
      the normal karyotype, higher SET expression group also had significantly shorter
      OS (12 months vs 35 months, P=0.010) and EFS (4 months vs 14 months, P=0.026)
      than of lower SET expression ones. CONCLUSION: High expression of SET gene was
      associated with poor prognosis and might be a prognostic molecular marker of AML.

PMID- 24857209
TI  - [Mechanism investigation of platelet apoptosis inhibition by N
      Arachidonoylethanolamine].
AB  - OBJECTIVE: To investigate the mechanism of N- Arachidonoylethanolamine (ANA) on
      inhibiting platelets (PLT) apoptosis under standard blood bank storage
      conditions. METHODS: Samples taken from collected apheresis PLT by the Amicus
      instrument were split into three parts. An aliquot of 0.5 MUmol/L ANA were added
      to one part of storage PLT as the ANA group; an aliquot of 0.5 MUmol/L ANA and 1
      MUmol/L SR141716 was added to the another part as the ANA + SR141716 group; and
      the third part without ANA and SR141716 as the control group. These samples were
      stored on a flat-bed shaker at (22 +/- 2) 0C for 7 days. The expression of
      phosphatidyl serine (PS) positive, phospho (p)-Akt, Akt, p-Bad, Bad, caspase-3,
      caspase-9, cytochrome C (Cyt-C) and BCL-XL interaction with Bak were detected.
      RESULTS: The rate of PLT PS positive in ANA group decreased significantly than
      that in control group[ (8.29 +/- 1.44) % vs (14.24 +/- 2.47) %, P<0.05]. The
      release of Cyt-C from mitochondria to cytosol in ANA group decreased
      significantly compared with control group[ (3.29 +/- 1.44) % vs (15.24 +/- 3.40)
      %, P<0.05]. Also the expressions of p-Akt and p-Bad in ANA group increased
      significantly than those in control group[ (71.33 +/- 10.26) % vs (35.00 +/-
      6.00) %, P<0.05; (39.00 +/- 9.64) % vs (10.33 +/- 1.53) %, P<0.05, respectively].
      Higher amounts of Bak protein were co-precipitated with BCL-XL in ANA group than
      that in control group (about 2.6 fold, P<0.05). The expressions of cleaved
      caspase- 9 and caspase- 3 in ANA group decreased significantly than those in
      control group[ (9.63 +/- 1.47) % vs (23.24 +/- 2.47) %, P<0.05; (6.30 +/- 1.40) %
      vs (13.20 +/- 2.50) %, P<0.05, respectively]. There were no significantly changes
      between ANA+SR141716 and control groups (P>0.05). CONCLUSION: ANA protected PLTs
      from apoptosis as a result of inhibiting the release of Cyt-C from mitochondria
      to cytosol by modifying the expressions of apoptosis-relative proteins.

PMID- 24857210
TI  - [Association of microRNA-related genes (DROSHA, DICER1 and GEMIN4) polymorphisms
      with T-cell lymphoma prognosis].
AB  - OBJECTIVE: To analyze the association of micoRNA-related genes DROSHA single
      nucleotide polymorphisms (SNP) rs10719 and rs6877842, DICER1 rs3742330and GEMIN4
      rs3744741 with prognosis of T-cell lymphoma. METHODS: Polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) method was used to determine
      the genotypes of the above 4SNPs and their associations with complete remission
      (CR) rate and overall survival (OS) in 163 patients with TCL. RESULTS: Patients
      carrying the rs6877842 CG genotype had a significantly higher CR rate compared
      with those carrying the CC genotype (OR=0.07, 95% CI 0.01-0.72, P=0.026); the
      same for patients carrying the DICER1 rs3742330 GG genotype compared with those
      carrying the GA genotype (OR=0.15, 95% CI 0.02-0.97, P=0.047) or the AA genotype
      (OR=0.11, 95% CI 0.02-0.71, P=0.020). In addition, patients with the DICER1
      rs3742330 GG genotype had a significantly improved OS compared with those
      carrying the GA (HR=9.02, 95% CI 1.22-66.92, P=0.031) or AA genotype (HR=8.77,
      95% CI 1.19-64.67, P=0.033). The other two SNPs of rs10719 and rs3744741 had no
      significant association with CR or OS. CONCLUSION: DROSHA rs6877842 and DICER1
      rs3742330 were independent factors for TCL CR, and DICER1 rs3742330 was also an
      independent prognostic factor for TCL OS.

PMID- 24857211
TI  - [Salvage therapy for severe aplastic anemia after allogenenic hematopoietic cell
      transplant].
AB  - OBJECTIVE: To probe a practical salvage strategy for relapse or failure patients
      with severe aplastic anemia (SAA) after allogenenic hematopoietic cell transplant
      (allo-HSCT). METHODS: The clinical characteristics and initial treatments of allo
      HSCT, and the responses of a novel salvage therapy of cyclosporine alternately
      combined with levamisole (CsA & LMS regimen) plus danazol (DNZ) in 2 patients
      were reviewed and evaluated. RESULTS: (1) Patient 1 achieved partial response
      (PR) at 3 months and complete response (CR) at 6 months after CsA & LMS regimen,
      respectively; Patient 2 also achieved PR 3 months and nearly CR at 6 months after
      the salvage therapy, respectively. (2) Increased numbers of T regulatory cells
      and colony forming unit-erythroid, burst-forming unit-erythroid, colony forming
      unit-granulocytes/macrophages after CsA & LMS regimen in both patients were
      observed. CONCLUSION: This was the first report of successful salvage by a novel
      strategy of CsA & LMS regimen for relapse or failure patients with SAA after allo
      HSCT.

PMID- 24857212
TI  - [Prevalence and molecular analysis of alpha-thalassemia in preschool children in
      Chongqing city].
AB  - OBJECTIVE: To investigate the incidence and the gene mutation frequencies and
      patterns of alpha-thalassemia in preschool children in Chongqing city. METHODS:
      Cluster random sampling was used. A total of 1057 preschool children in three
      areas of Chongqing were screened by using routine blood test and hemoglobin
      electrophoresis analysis. Molecular analysis carried out for all the samples.
      RESULTS: Of the 1057 samples, 55 cases were diagnosed as being carriers of alpha
      thalassemia, which included 80 allele genes. Therefore, the frequency of alpha
      thalassemia carriers in Chongqing was 5.20%. Of the 55 alpha-thalassemia
      carriers, five different deletions of alpha-thalassemia were identified, the
      three most common deletion types and proportions were 54.55% for the -alpha(3.7)
      deletion, 18.18% for --(SEA) deletion, and 9.08% for the -alpha(4.2) deletion,
      respectively; eight types of nondeletion defects were determined, containing one
      case of Hb Quong Sze and seven novel mutations of a-globin gene. Furthermore, 24
      cases of alpha-Triplication were detected with the alpha-Triplication carrier
      rate of 2.55%. In addition, in this study we also found two cases of abnormal
      hemoglobin disorders occurred on alpha-globin gene, Hb J-Wenchang-Wuming and Hb
      Arya. Hb Arya was characterized in the Chinese population for the first time
      confirmed by literature retrieval. CONCLUSION: In this study, we have clarified
      the carrier frequency and molecular spectrum of alpha-thalassemia in Chongqing,
      and we first reported the carrier incidence of alpha-Triplication in Chongqing.
      The materials obtained from this study would be of valuable reference for genetic
      counseling and the examination instruction of children in this area.

PMID- 24857213
TI  - [Clinical study on cytomegalovirus infection after hematopoietic stem cell
      transplantation in 26 patients with primary immunodeficiency diseases].
AB  - OBJECTIVE: To explore the risk factors, and control measures of cytomegalovirus
      (CMV) infection after hematopoietic stem cell transplantion (HSCT) in children
      with primary immunodeficiency diseases(PID). METHODS: We retrospectively analyzed
      results of 26 patients with PID-Wiskott-Aldrich syndrome (WAS, n=20), severe
      combined immunodeficiency (SCID, n=1) , X-linked chronic granulomatous disease
      (XCGD, n=2) and X-linked hyper-immunoglobulin M (IgM) syndrome (XHIM, n=3)-who
      underwent HSCT from June 2007 to December 2012 in our center. Serologic studies
      (ELISA) and weekly CMV infection surveillance (quantitative PCR, qPCR) were
      routinely performed before and after HSCT. Ganciclovir or forcarnet was used for
      pre-emptive and curative therapy. RESULTS: All 26 patients were male with the
      median age at HSCT of 27 months (range 7-77 months). At a median follow up of 24
      months (range 5-66 months), the 5-year overall survival rate was (75.0 +/- 9.0)
      %. CMV infection occurred in 42.3% (11 of 26) of the patients, two of them
      developed CMV interstitial pneumonia (CMVIP). Univariate analysis revealed that
      the incidence of pre-transplant CMV infection between with and without CMV
      activation groups after HSCT was significantly different (62.5% vs 10.0%,
      P=0.010). Additional variables not associated with CMV infection were stem-cell
      sources, donor type, HLA disparity and acute GVHD (all P values>0.05).
      CONCLUSION: CMV infection was a major complication of HSCT. Sensitive monitoring,
      early diagnosis, timely treatment may improve the survival rate for these PID
      undergoing HSCT.

PMID- 24857214
TI  - [Impact of graft versus host disease on outcome of allogeneic peripherial blood
      stem cell transplantation for leukemia].
AB  - OBJECTIVE: To analyze the impact of the occurrence and severity of acute and
      chronic graft versus host disease (GVHD) on the long-term outcome of allogeneic
      peripheral blood stem cell transplantation (allo-PBSCT) for leukemia. METHODS: A
      total of 231 patients with leukemia, who underwent allo-HSCT in Changhai Hospital
      from Jan 1st, 2001 to Dec 31th, 2011, were retrospectively analyzed. The overall
      survival (OS), disease-free survival (DFS), transplantation-related mortality
      (TRM) and relapse rate (RR) were estimated according to the degree of acute and
      chronic GVHD. RESULTS: (1) Among the 224 assessable patients, aGVHD was observed
      in 85 patients, in which 46 developed grade I, 25 grade II and 14 grade III-IV. A
      total of 213 patients who survived beyond 100 days, cGVHD was observed in 109
      patients, in which 84 developed limited cGVHD and 25 extensive cGVHD. (2)The
      incidence of 3-year OS and EFS of patients with aGVHD grade 0-I was significantly
      higher than that of grade II-IV (69.5% vs 33.6%, P<0.01; 60.7% vs 33.7%, P<0.01).
      The 3-year TRM of patients with 0-I grade aGVHD was significantly lower than that
      of the grade II-IV group (15.0% vs 56.7%, P<0.01). (3)The 5-year OS of patients
      with limited cGVHD was higher than patients without or with extensive cGVHD
      (79.8% vs 55.6% and 56.4%, P<0.01 and P=0.038, respectively). The 5-year TRM in
      patients with extensive cGVHD was higher than patients with limited cGVHD (14.1%
      vs 41.1%, P=0.018). However, the 5-year RR in patients without cGVHD was higher
      than patients with limited cGVHD or extensive cGVHD (47.2% vs 10.9% and 12.4%,
      P<0.01 and P=0.007, respectively). (4) The COX analysis showed that unrelated
      donor and myeloablative conditioning regimen were main factors affecting aGVHD;
      Meanwhile, aGVHD was the only factor affecting the cGVHD. CONCLUSION: Our results
      showed that the patients with acute GVHD tended to have poor outcomes, especially
      with grade III-IV. On the contrary, the patients with limited cGVHD had lower RR
      and a long-term DFS.

PMID- 24857215
TI  - [Ultrasonographic characteristics of haemophilic arthropathy in the knee joints].
AB  - OBJECTIVE: To investigate the characteristics of ultrasonography in haemophilic
      arthropathy in knee joints. METHODS: The knee joints (n=135) of 68 patients with
      haemophilia A (n=59) or haemophilia B (n=9) were consecutively evaluated with
      ultrasonography and scored according to MELCHIORRE ultrasound score. The
      correlations between ultrasound score and the number of knee joint bleeding
      episodes, age, and World Federation Haemophilic orthopedic (WFHO) score were
      studied. RESULTS: 68 male patients with median age 20 (3-48) years old were
      enrolled in this study. The prevalences of hydrops articuli, fibrotic septa,
      synovial hypertrophy, synovial hypertrophy with angiogenesis, haemosiderin
      deposition were 39.2% (53/135), 3.0% (4/135), 77.0% (104/135), 49.6% (67/135),
      37.8% (51/135), respectively; and the prevalences of cartilage damage, bone
      erosion, bone remodeling, osteophytes were 63.7% (86/135), 48.1% (65/135), 3.0%
      (4/135), 13.3% (18/135) respectively. The average ultrasound score was 5.21[95%
      CI (4.50-5.93)]. The ultrasound score of knees joints according to age 0-6, 7-18
      and > 18 years old groups were 0.63[95% CI (0.15-1.10)], 2.88[95% CI (1.90
      3.85)], 7.83[95% CI (7.07-8.60)], respectively; and the difference among groups
      was statistically significant (P<0.01). The significant difference of ultrasound
      score was not found among moderate, mild and severe haemophilia (F=0.90,
      P=0.914). A significant positive correlation between ultrasound and WFHO scores
      was demonstrated (r=0.745, P<0.01). The ultrasound score increased significantly
      with the increase of number of knee bleed Episodes (F=49.926, P<0.01).
      CONCLUSION: The main characteristics of ultrasonography of haemophilic
      arthropathy in knee joints were identified as followings: synovial hypertrophy,
      cartilage damage, bone erosion, hydrops articuli, and haemosiderin deposition.
      Ultrasonography was a fast, effective, safe, and available inspection method in
      assessment of haemophilic arthropathy.

PMID- 24857216
TI  - [Up-regulation of NKG2D ligand ULBP2 by matrine in K562 cells and the underlying
      molecular mechanisms].
AB  - OBJECTIVE: To probe matrine acting on natural killer cell (NK) activating
      receptor NKG2D ligands expression in CML cell line K562 and its underlying
      molecular mechanism. METHODS: The expression of NKG2D ligands (major
      histocompatibility complex class I chain-related molecule A or B (MICA/B), UL16
      binding proteins (ULBP) 1, 2, and 3 on K562 cells were analyzed before and after
      treated with matrine by FCM. The cytotoxic sensitivity of K562 to NK cell was
      detected by FCM after CFSE staining at different effect-to-target (E/T) cell
      ratios. The expression of signal transduction and transcriptional activator 3
      (STAT3) protein as well as phosphorylated STAT3 (p-STAT3) were detected by
      western blot. RESULTS: After treatment with matrine, ULBP1 and ULBP2 expression,
      especially ULBP2 on K562 cells significantly increased, with mean fluorescence
      intensity (MFI) increasing to 615 and 1614 by 220 and 615 in the untreated cells,
      respectively. There was no significant change for MICA or ULBP3 expression.
      Matrine enhanced the susceptibility of K562 cells to NK-mediated cell lysis. At
      the ratio of E/T with 5:1, the proportion of the killed K562 cells increased to
      32.8%, 38.1% and 40.5%, respectively (after 0.2, 0.5 and 0.8 mg/ml matrine
      treatment) by 29.2% in the untreated cells. The phosphorylated STAT3 protein, but
      not STAT3 protein, was significantly inhibited by matrine treatment in K562
      cells. CONCLUSION: Matrine induced the expression of NKG2D ligands in K562cells
      and enhanced the cytotoxicity of NK cells against K562, which was closely related
      to the inhibition of STAT3 activity in K562 cell.

PMID- 24857217
TI  - [Triptolide affect the methylation status of HL-60cells].
AB  - OBJECTIVE: To study the effect of triptolide (TP) on the methylation status of
      human promyelocytic leukemia cells (HL-60) and explore a preliminary
      demethylation mechanism. METHODS: Normal HL-60 cells as control group, the cell
      proliferation level of HL-60 cells was detected by MTT assay, being treated by
      different concentration TP (3.125, 6.25, 12.5, 25 nmol/L) for 24 h or 48 h
      respectively; Choosing the 3.125 nmol/L and the 6.25 nmol/L TP affected HL-60
      cells for 48 h, the cell apoptosis rate and cell cycle were determined by flow
      cytometry, the expressions of death-associated protein kinase 1 (DAPK-1) and
      methyltransferase DNMT1, DNMT3B mRNA were measured by real time-PCR (RT-PCR),
      LINE-1, DAPK-1 genes'methylation variations were analyzed by methylation specific
      PCR (MSP). RESULTS: Compared with control group, the different concentration TP
      could significantly inhibit the proliferation of HL-60 in a time-dose dependent
      manner (P<0.05, P<0.01). After being treated by TP for 48 h, the cell early
      apoptosis rate of control group and 6.250 nmol/L TP group were (2.07 +/- 1.91)%,
      (9.77 +/- 3.52)%, respectively (P<0.05); When the TP concentration increased,
      DAPK-1mRNA expression increased (P<0.01), DNMT1, DNMT3B mRNA expression
      significantly dampened (P<0.01); the promoter of LINE-1, DAPK-1 genes were
      hypermethylation state in the control group, after being treated by TP for 48 h,
      the brightness of LINE-1, DAPK-1 genes'methylation strips weakened, and the non
      methylation strips enhanced all in a dose-dependent manner. CONCLUSION: TP could
      down-regulate the transcriptional expression of methyltransferase DNMT1/3B genes,
      indirect action to reduce the degree of DAPK-1, LINE-1 genes mathylation, thus
      promote DAPK-1 gene expression level and inhibit the HL 60 cell growth.

PMID- 24857218
TI  - [Analysis of Bortezomib-containing combinations in newly-diagnosed multiple
      myeloma patients: a comparative study].

PMID- 24857219
TI  - [Porcine anti-human lymphocyte immunoglobulin plus cydosporine in the treatment
      of severe aplastic anemia].

PMID- 24857220
TI  - [The retrospective analysis of prophylactic administration of pegylated
      recombinant human granulocyte colony stimulating factor in lymphoma patients
      undergoing chemotherapy].

PMID- 24857221
TI  - [A multicenter study of rituximab-based regimen as first-line treatment in
      patients with follicular lymphoma].

PMID- 24857222
TI  - [The clinical observation of low dose of heparin to treat coagulation disorders
      of acute promyelocytic leukemia].

PMID- 24857223
TI  - [Diffuse large B cell lymphoma arising from unicentric Castleman's disease: a
      case report and literature review].

PMID- 24857224
TI  - [Interleukin-16 levels in 42 cases patients with multiple myeloma and its
      clinical significance].

PMID- 24857225
TI  - [Tumor microenvironment in pathogenesis and drug resistance of non-Hodgkin's
      lymphoma].

PMID- 24857226
TI  - [Advances of MYC oncoprotein in tumorigenesis through metabolism pathway].

PMID- 24857227
TI  - [Chinese guidelines for diagnosis and treatment of acute promyelocytic leukemia
      (2014)].

PMID- 24857228
TI  - [Interpretation of the expert Chinese guideline for diagnosis and treatment of
      acute promyelocytic leukemia (2014)].

PMID- 24857229
TI  - [Hotpots of the 55th American society of hematology annual meeting: red blood
      cell disorders].

PMID- 24857230
TI  - [A case report of dasatinib-induced tumor lysis syndrome].

PMID- 24857232
TI  - Successful outcomes with thrombolysis for limb ischemia with suprainguinal
      interventions, but high limb loss and mortality for infrainguinal disease.

PMID- 24857233
TI  - Limited agreement between biomarkers of neuronal injury at different stages of
      Alzheimer's disease.
AB  - New diagnostic criteria for Alzheimer's disease (AD) treat different biomarkers
      of neuronal injury as equivalent. Here, we quantified the degree of agreement
      between hippocampal volume on structural magnetic resonance imaging, regional
      glucose metabolism on positron emission tomography, and levels of phosphorylated
      tau in cerebrospinal fluid (CSF) in 585 subjects from all phases of the AD
      Neuroimaging Initiative. The overall chance-corrected agreement was poor (Cohen
      kappa, 0.24-0.34), in accord with a high rate of conflicting findings (26%-41%).
      Neither diagnosis nor APOE epsilon4 status significantly influenced the
      distribution of agreement between the biomarkers. The degree of agreement tended
      to be higher in individuals with abnormal versus normal CSF beta-amyloid (Abeta1
      42) levels. Prospective diagnostic criteria for AD should address the relative
      importance of markers of neuronal injury and elaborate a way of dealing with
      conflicting biomarker findings. 

PMID- 24857235
TI  - An integrated analysis of match-related fatigue in professional rugby league.
AB  - This study examined the changes in external outputs, including metabolic power
      variables, and internal response whilst considering contextual factors on
      physical performance variables during rugby league match play. Physical
      performance (total distance, high-speed running and high-power distances, average
      metabolic power), heart-rate (percentage heart-rate peak and training impulse),
      collisions (attacking and defensive) and contextual (time in attack, time in
      defence, time out of play) data were collected from 18 rugby league players
      during 38 games throughout two National Rugby League seasons. Physical variables
      were highest in the first 10-min period of each half (P < 0.001). Heart-rate
      indices peaked in the second 10-min period and were lower during second half
      periods (P < 0.001). Few differences existed in collisions and contextual factors
      across 10-min periods. Physical variables were highest during the first 5-min
      period compared to the final (P < 0.001). There was no difference in heart-rate
      response, attacking collisions or contextual factors between these periods.
      Following the peak 5-min period in the match, there were reductions in physical,
      heart-rate, defensive collisions and contextual factors (P < 0.001). The data
      show temporal changes in physical performance, heart-rate response and collisions
      during rugby league match play, although these are affected by contextual
      factors.

PMID- 24857234
TI  - Susceptibility of the conventional criteria for mild cognitive impairment to
      false-positive diagnostic errors.
AB  - BACKGROUND: We assessed whether mild cognitive impairment (MCI) subtypes could be
      empirically derived within the Alzheimer's Disease Neuroimaging Initiative (ADNI)
      MCI cohort and examined associated biomarkers and clinical outcomes. METHODS:
      Cluster analysis was performed on neuropsychological data from 825 MCI ADNI
      participants. RESULTS: Four subtypes emerged: (1) dysnomic (n = 153), (2)
      dysexecutive (n = 102), (3) amnestic (n = 288), and (4) cluster-derived normal (n
      = 282) who performed within normal limits on cognitive testing. The cluster
      derived normal group had significantly fewer APOE epsilon4 carriers and fewer who
      progressed to dementia compared with the other subtypes; they also evidenced
      cerebrospinal fluid Alzheimer's disease biomarker profiles that did not differ
      from the normative reference group. CONCLUSIONS: Identification of empirically
      derived MCI subtypes demonstrates heterogeneity in MCI cognitive profiles that is
      not captured by conventional criteria. The large cluster-derived normal group
      suggests that conventional diagnostic criteria are susceptible to false-positive
      errors, with the result that prior MCI studies may be diluting important
      biomarker relationships.

PMID- 24857237
TI  - Humic acid acts as a natural antidote of graphene by regulating nanomaterial
      translocation and metabolic fluxes in vivo.
AB  - Graphene-related research has intensified rapidly in a wide range of disciplines,
      but few studies have examined ecosystem risks, particularly phytotoxicity. This
      study revealed that graphene significantly inhibits the number of wheat roots and
      the biosynthesis of chlorophyll, and altered the morphology of shoots. Humic acid
      (HA), a ubiquitous form of natural organic matter, significantly (P < 0.05)
      relieved this phytotoxicity and recovered the sharp morphology of shoot tips.
      Both graphene and graphene-HA were transferred from wheat roots to shoots and
      were found in the cytoplasms and chloroplasts. HA increased the disordered
      structure and surface negative charges, and reduced the aggregation of graphene.
      HA enhanced the storage of graphene in vacuoles, potentially indicating an
      effective detoxification path. The content of cadaverine, alkane, glyconic acid,
      and aconitic acid was up-regulated by graphene, greatly contributing to the
      observed phytotoxicity. Conversely, inositol, phenylalanine, phthalic acid, and
      octadecanoic acid were up-regulated by graphene-HA. The metabolic pathway
      analysis revealed that the direction of metabolic fluxes governed nanotoxicity.
      This work presents the innovative concept that HA acts as a natural antidote of
      graphene by regulating its translocation and metabolic fluxes in vivo. This
      knowledge is critical for avoiding the overestimation of nanomaterial risks and
      can be used to control nanomaterial contamination. 

PMID- 24857238
TI  - Is the Theory of Mind deficit observed in visual paradigms in schizophrenia
      explained by an impaired attention toward gaze orientation?
AB  - Schizophrenia is associated with poor Theory of Mind (ToM), particularly in goal
      and belief attribution to others. It is also associated with abnormal gaze
      behaviors toward others: individuals with schizophrenia usually look less to
      others' face and gaze, which are crucial epistemic cues that contribute to
      correct mental states inferences. This study tests the hypothesis that impaired
      ToM in schizophrenia might be related to a deficit in visual attention toward
      gaze orientation. We adapted a previous non-verbal ToM paradigm consisting of
      animated cartoons allowing the assessment of goal and belief attribution. In the
      true and false belief conditions, an object was displaced while an agent was
      either looking at it or away, respectively. Eye movements were recorded to
      quantify visual attention to gaze orientation (proportion of time participants
      spent looking at the head of the agent while the target object changed
      locations). 29 patients with schizophrenia and 29 matched controls were tested.
      Compared to controls, patients looked significantly less at the agent's head and
      had lower performance in belief and goal attribution. Performance in belief and
      goal attribution significantly increased with the head looking percentage. When
      the head looking percentage was entered as a covariate, the group effect on
      belief and goal attribution performance was not significant anymore. Patients'
      deficit on this visual ToM paradigm is thus entirely explained by a decreased
      visual attention toward gaze. 

PMID- 24857239
TI  - Detection of almond allergen coding sequences in processed foods by real time
      PCR.
AB  - The aim of this work was to develop and analytically validate a quantitative RT
      PCR method, using novel primer sets designed on Pru du 1, Pru du 3, Pru du 4, and
      Pru du 6 allergen-coding sequences, and contrast the sensitivity and specificity
      of these probes. The temperature and/or pressure processing influence on the
      ability to detect these almond allergen targets was also analyzed. All primers
      allowed a specific and accurate amplification of these sequences. The specificity
      was assessed by amplifying DNA from almond, different Prunus species and other
      common plant food ingredients. The detection limit was 1 ppm in unprocessed
      almond kernels. The method's robustness and sensitivity were confirmed using
      spiked samples. Thermal treatment under pressure (autoclave) reduced yield and
      amplificability of almond DNA; however, high-hydrostatic pressure treatments did
      not produced such effects. Compared with ELISA assay outcomes, this RT-PCR showed
      higher sensitivity to detect almond traces in commercial foodstuffs. 

PMID- 24857241
TI  - Effect of primary empty sella syndrome on pituitary surgery for Cushing's
      disease.
AB  - OBJECT: Primary empty sella syndrome (ESS) results from herniation of arachnoid
      mater into the pituitary fossa. It has been suggested to have a negative effect
      on pituitary surgery; however, outcomes in this cohort have not been defined.
      This study was performed to determine the effect of ESS on immediate and long
      term biochemical outcome after pituitary surgery for Cushing's disease (CD).
      METHODS: Using a matched cohort study design, the authors followed patients
      treated with pituitary surgery for CD with and without ESS. Complete ESS was
      defined as pituitary gland height <= 2 mm, whereas partial ESS was defined as
      pituitary gland height > 2 mm but less than three-quarters of the total sellar
      depth. The primary end points were immediate and long-term biochemical outcome.
      Cerebrospinal fluid leaks were recorded as a secondary end point. RESULTS:
      Seventy-eight patients with CD and primary ESS were identified and matched with
      78 patients with CD without ESS. After surgical management, immediate biochemical
      remission was achieved in 69 patients (88%) with ESS and 75 controls (96%, p =
      0.10). Long-term remission was achieved in most patients in both groups (5-year
      cure: 85% vs 92%, p = 0.10). Among patients with ESS, the presence of complete
      ESS predicted a worse long-term outcome (p = 0.04). Intraoperative CSF leaks were
      significantly more frequent with ESS (54% vs 24%, p < 0.001), and despite sellar
      floor repair, the rate of postoperative CSF leaks was also increased (6% vs 3%, p
      = 0.27). CONCLUSIONS: Biochemical outcome after pituitary surgery for CD was
      worse in patients with complete ESS, and the risk of a CSF leak was increased
      with both partial and complete ESS. However, as outcome remains superior to those
      following alternative therapies and the biology of these tumors is unchanged in
      the setting of ESS, pituitary surgery should remain the initial treatment of
      choice.

PMID- 24857242
TI  - Survival after surgery and stereotactic radiosurgery for patients with multiple
      intracranial metastases: results of a single-center retrospective study.
AB  - OBJECTIVES: Patients with systemic cancer and a single brain metastasis who
      undergo treatment with resection plus radiotherapy live longer and have a better
      quality of life than those treated with radiotherapy alone. Historically, whole
      brain radiotherapy (WBRT) has been the mainstay of radiation therapy; however, it
      is associated with significant delayed neurocognitive sequelae. In this study,
      the authors looked at survival in patients with single and multiple intracranial
      metastases who had undergone surgery and adjuvant stereotactic radiosurgery (SRS)
      to the tumor bed and synchronous lesions. METHODS: The authors retrospectively
      reviewed the records from an 8-year period at a single institution for
      consecutive patients with brain metastases treated via complete resection of
      dominant lesions and adjuvant radiosurgery. The cohort was analyzed for time to
      local progression, synchronous lesion progression, new intracranial lesion
      development, systemic progression, and overall survival. The Kaplan-Meier method
      (stratified by age, sex, tumor histology, and number of intracranial lesions
      prior to surgery) was used to calculate both progression-free and overall
      survival. A Cox proportional-hazards regression model was also fitted with the
      number of intracranial lesions as the predictor and survival as the outcome
      controlling for disease severity, age, sex, and primary histology. RESULTS: The
      median overall follow-up among the 150-person cohort eligible for analysis was 17
      months. Patients had an average age of 46.2 years (range 16-82 years), and 62.7%
      were female. The mean (+/- standard deviation) number of intracranial lesions per
      patient was 2.5 +/- 2.3. The mean time between surgery and stereotactic
      radiosurgery (SRS) was 3.2 +/- 4.1 weeks. Primary cancers included lung cancer
      (43.3%), breast cancer (21.3%), melanoma (10.0%), renal cell carcinoma (6.7%),
      and colon cancer (6.7%). The average number of isocenters per treated lesion was
      7.6 +/- 6.6, and the average treatment dose was 17.8 +/- 2.8 Gy. One-year
      survival for patients in this cohort was 52%, and the 1-year local control rate
      was 77%. The median (+/-standard error) overall survival was 13.2 +/- 1.9 months.
      There was no difference in survival between patients with a single lesion and
      those with multiple lesions (p = 0.319) after controlling for age, sex, and
      histology of primary tumor. Patients with primary breast histology had the
      greatest overall median survival (22.9 +/- 6.2 months); patients with colorectal
      cancer had the shortest overall median survival (5.3 +/- 1.8 months). The most
      common cause of death in this series was systemic progression (79%). CONCLUSIONS:
      These results confirm that 1-year survival for patients with multiple
      intracranial metastases treated with resection followed by SRS to both the tumor
      bed and synchronous lesions is similar to established outcomes for patients with
      a single intracranial metastasis.

PMID- 24857243
TI  - Diagnostic accuracy of intraocular pressure measurement for the detection of
      raised intracranial pressure: meta-analysis: a systematic review.
AB  - OBJECT: Because clinical examination and imaging may be unreliable indicators of
      intracranial hypertension, intraocular pressure (IOP) measurement has been
      proposed as a noninvasive method of diagnosis. The authors conducted a systematic
      review and meta-analysis to determine the correlation between IOP and
      intracranial pressure (ICP) and the diagnostic accuracy of IOP measurement for
      detection of intracranial hypertension. METHODS: The authors searched
      bibliographic databases (Ovid MEDLINE, Ovid EMBASE, and the Cochrane Central
      Register of Controlled Trials) from 1950 to March 2013, references of included
      studies, and conference abstracts for studies comparing IOP and invasive ICP
      measurement. Two independent reviewers screened abstracts, reviewed full-text
      articles, and extracted data. Correlation coefficients, sensitivity, specificity,
      and positive and negative likelihood ratios were calculated using DerSimonian and
      Laird methods and bivariate random effects models. The I(2) statistic was used as
      a measure of heterogeneity. RESULTS: Among 355 identified citations, 12 studies
      that enrolled 546 patients were included in the meta-analysis. The pooled
      correlation coefficient between IOP and ICP was 0.44 (95% CI 0.26-0.63, I(2) =
      97.7%, p < 0.001). The summary sensitivity and specificity for IOP for diagnosing
      intracranial hypertension were 81% (95% CI 26%-98%, I(2) = 95.2%, p < 0.01) and
      95% (95% CI 43%-100%, I(2) = 97.7%, p < 0.01), respectively. The summary positive
      and negative likelihood ratios were 14.8 (95% CI 0.5-417.7) and 0.2 (95% CI 0.02
      1.7), respectively. When ICP and IOP measurements were taken within 1 hour of
      another, correlation between the measures improved. CONCLUSIONS: Although a
      modest aggregate correlation was found between IOP and ICP, the pooled diagnostic
      accuracy suggests that IOP measurement may be of clinical utility in the
      detection of intracranial hypertension. Given the significant heterogeneity
      between included studies, further investigation is required prior to the adoption
      of IOP in the evaluation of intracranial hypertension into routine practice.

PMID- 24857244
TI  - The skull of Chios: trepanation in Hippocratic medicine.
AB  - Cranial trepanation is the oldest neurosurgical operation and its roots date back
      to prehistory. For many centuries, religion and mysticism were strongly linked to
      the cause of diseases, and trepanation was associated with superstitions such as
      releasing evil spirits from inside the skull. The Hippocratic treatise "On
      injuries of the head" was therefore a revolutionary work, as it presented a
      systematic approach to the management of cranial trauma, one that was devoid of
      spiritual elements. Unfortunately, there are only a limited number of skeletal
      findings that confirm that the practice of trepanation was performed as part of
      Hippocratic medicine. In this historical vignette, the authors present a
      trepanned skull that was found in Chios, Greece, as evidence of the procedure
      having been performed in accordance with the Hippocratic teaching. The skull
      bears a parietal bur hole in association with a linear fracture, and it is clear
      that the patient survived the procedure. In this analysis, the authors examine
      the application of the original Hippocratic teaching to the skull of Chios. The
      rationalization of trepanation was clearly a significant achievement in the
      evolution of neurosurgery. 

PMID- 24857245
TI  - Bartonella spp. and Yersinia pestis reservoirs, Cusco, Peru.

PMID- 24857246
TI  - Experience of an ED physician providing patients with personal contact
      information.

PMID- 24857247
TI  - Ultra-long cardiopulmonary resuscitation with thrombolytic therapy for a sudden
      cardiac arrest patient with pulmonary embolism.
AB  - The recovery of cardiac arrest patients with pulmonary embolism who are given an
      ultra-long duration of cardiopulmonary resuscitation(CPR) with manual chest
      compressions is very rare. We reported a 52-year-old woman who came to the
      hospital because of paroxysmal dyspnea. She experienced in hospital cardiac
      arrest and underwent prolonged CPR with manual chest compressions for 160
      minutes. The patient presented with several episodes of cardiac electrical
      activity that lasted 10 to 20 seconds without consciousness. Blood gas analysis
      revealed pH 7.27, PaO2 51 mm Hg, and D-dimer 3723 ig/mL. In addition,acute
      pulmonary embolism was considered due to the patient's symptoms. Thrombolytic
      therapy was given 100 minutes after the CPR was implemented. Sixty minutes later,
      her sinus rhythm was restored.After the continuous renal replacement therapy for
      renal failure was administered and other conservative treatments were given for
      the complications after the CPR with thrombolytic therapy, she finally recovered
      and was discharged. This case report supports the use of persistent ongoing CPR
      efforts and the use of thrombolytic therapy.

PMID- 24857249
TI  - Erythropoietin administration facilitates return of spontaneous circulation and
      improves survival in a pig model of cardiac arrest.
AB  - BACKGROUND: In addition to its role in the endogenous control of erythropoiesis,
      recombinant human erythropoietin (rh-EPO) has been shown to exert tissue
      protective properties in various experimental models. However, its role in the
      cardiac arrest (CA) setting has not yet been adequately investigated. AIM: The
      aim of this study is to examine the effect of rh-EPO in a pig model of
      ventricular fibrillation (VF)-induced CA. METHODS: Ventricular fibrillation was
      electrically induced in 20 piglets and maintained untreated for 8 minutes before
      attempting resuscitation. Animals were randomized to receive rh-EPO (5000 IU/kg,
      erythropoietin [EPO] group, n = 10) immediately before the initiation of chest
      compressions or to receive 0.9% Sodium chloride solution instead (control group,
      n = 10). RESULTS: Compared with the control, the EPO group had higher rates of
      return of spontaneous circulation (ROSC) (100% vs 60%, P = .011) and higher 48
      hour survival (100% vs 40%, P = .001). Diastolic aortic pressure and coronary
      perfusion pressure during cardiopulmonary resuscitation were significantly higher
      in the EPO group compared with the control group. Erythropoietin-treated animals
      required fewer number of shocks in comparison with animals that received normal
      saline (P = .04). Furthermore, the neurologic alertness score was higher in the
      EPO group compared with that of the control group at 24 (P = .004) and 48 hours
      (P = .021). CONCLUSION: Administration of rh-EPO in a pig model of VF-induced CA
      just before reperfusion facilitates ROSC and improves survival rates as well as
      hemodynamic variables.

PMID- 24857248
TI  - ED disposition of the Glasgow Coma Scale 13 to 15 traumatic brain injury patient:
      analysis of the Transforming Research and Clinical Knowledge in TBI study.
AB  - OBJECTIVE: Mild traumatic brain injury (mTBI) patients are frequently admitted to
      high levels of care despite limited evidence suggesting benefit. Such decisions
      may contribute to the significant cost of caring for mTBI patients. Understanding
      the factors that drive disposition decision making and how disposition is
      associated with outcomes is necessary for developing an evidence-base supporting
      disposition decisions. We evaluated factors associated with emergency department
      triage of mTBI patients to 1 of 3 levels of care: home, inpatient floor, or
      intensive care unit (ICU). METHODS: This multicenter, prospective, cohort study
      included patients with isolated head trauma, a cranial computed tomography as
      part of routine care, and a Glasgow Coma Scale (GCS) score of 13 to 15. Data
      analysis was performed using multinomial logistic regression. RESULTS: Of the 304
      patients included, 167 (55%) were discharged home, 76 (25%) were admitted to the
      inpatient floor, and 61 (20%) were admitted to the ICU. In the multivariable
      model, admission to the ICU, compared with floor admission, varied by study site,
      odds ratio (OR) 0.18 (95% confidence interval [CI], 0.06-0.57);
      antiplatelet/anticoagulation therapy, OR 7.46 (95% CI, 1.79-31.13); skull
      fracture, OR 7.60 (95% CI, 2.44-23.73); and lower GCS, OR 2.36 (95% CI, 1.05
      5.30). No difference in outcome was observed between the 3 levels of care.
      CONCLUSION: Clinical characteristics and local practice patterns contribute to
      mTBI disposition decisions. Level of care was not associated with outcomes.
      Intracranial hemorrhage, GCS 13 to 14, skull fracture, and current
      antiplatelet/anticoagulant therapy influenced disposition decisions.

PMID- 24857250
TI  - Spontaneous spinal epidural hematoma after abrupt sneezing with prompt recovery
      of severe paraparesis.
AB  - Spontaneous spinal epidural hematoma (SSEH) is a rare neurologic condition with
      threatening consequences when spinal cord compression is present. The diagnosis
      must be performed quickly using magnetic resonance imaging (MRI), which shows
      collection of blood in the epidural space. With spinal cord compression, there is
      an indication for urgent surgical decompression. Here, we present a 64-year-old
      woman who developed sudden thoracic and lower back pain accompanied by severe
      paraparesis and urinary retention after sneezing abruptly. An MRI revealed a
      posterior thoracic epidural hematoma extending from the T6 to T11 vertebral level
      with spinal cord compression. Decompression was recommended, but the patient
      refused surgery, while neurologically improving with time. Complete neurologic
      recovery was observed within 24 hours after SSEH onset. A conservative
      therapeutic approach with careful observation may therefore be considered as a
      treatment of choice in some cases where surgery is refused, (due to high risk or
      other reasons) and neurologic recovery is early and sustained.

PMID- 24857251
TI  - Impact of initial blood pressure on antihypertensive response in patients with
      acute hypertension.
AB  - INTRODUCTION: The effect profile of differing antihypertensive agents is well
      studied, but minimal data regarding the interaction between hemodynamic response
      and presenting blood pressure (BP) exist. HYPOTHESIS: Achievement of target BP is
      less likely in patients with higher initial BPs. METHODS: This is a substudy of
      the multicenter safety and efficacy Evaluation of intravenous Cardene
      (nicardipine) and Labetalol Use in the Emergency department (CLUE) trial that
      randomized patients to Food and Drug Administration-recommended intravenous
      dosing of nicardipine or labetalol to reach a physician predefined systolic BP
      (SBP) and target range (TR) of +/-20 mm Hg within 30 minutes. The proportion
      achieving TR was assessed as a function of initial SBP, and dichotomized
      comparisons were made using median SBP. Likelihood of a final BP within TR was
      modeled using logistic regression with forced inclusion of initial BP as a
      categorical variable. RESULTS: A total 223 patients were enrolled; 115 (51.6%)
      had an initial SBP greater than the median 202 mm Hg. The median SBP
      (interquartile range) of the high BP group was 218 (210-228) mm Hg vs the low BP
      group 190 (182-197) mm Hg (P < 0.0001). No groupwise differences existed except
      that the high group had higher mean (SD) serum creatinine level at baseline (3.1
      [3.9] vs 1.9 [2.3], P = .008). The proportion of patients achieving SBP within TR
      at 30 minutes did not differ (85.2% [98 of 115] vs 88.9% [96 of 108], P = .42).
      Randomization to nicardipine (odds ratio = 2.85; 95% confidence interval, 1.16
      7.01), but not initial SBP (odds ratio = 0.60; 95% confidence interval, 0.25
      1.44), was associated with achievement of target SBP at 30 minutes. CONCLUSION:
      Initial SBP is not a predictor of the ability to achieve a prespecified target
      range SBP within 30 minutes.

PMID- 24857252
TI  - Alveolar macrophages are the main target cells in feline calicivirus-associated
      pneumonia.
AB  - Feline calicivirus (FCV) is a pathogen of felids and one of the most common
      causative agents of feline upper respiratory disease (URD). Reports of natural
      FCV pneumonia in the course of respiratory tract infections are sparse.
      Therefore, knowledge on the pathogenesis of FCV-induced lung lesions comes only
      from experimental studies. The aim of the present study was to assess the type
      and extent of pulmonary involvement in natural respiratory FCV infections of
      domestic cats and to identify the viral target cells in the lung. For this
      purpose, histology, immunohistochemistry and RNA-in situ hybridisation for FCV
      and relevant cell markers were performed on diagnostic post-mortem specimens
      collected after fatal URD, virulent systemic FCV or other conditions. All groups
      of cats exhibited similar acute pathological changes, dominated by multifocal
      desquamation of activated alveolar macrophages (AM) and occasional type II
      pneumocytes with fibrin exudation, consistent with diffuse alveolar damage (DAD).
      In fatal cases, this was generally seen without evidence of epithelial
      regeneration. In cats without clinical respiratory signs, type II pneumocyte
      hyperplasia was present alongside the other changes, consistent with the post
      damage proliferative phase of DAD. FCV infected and replicated in AM and, to a
      lesser extent, type II pneumocytes. This study shows that lung involvement is an
      infrequent but important feature of FCV-induced URD. AM are the main viral target
      cell and pulmonary replication site, and their infection is associated with
      desquamation and activation, as well as death via apoptosis.

PMID- 24857253
TI  - An update on feline infectious peritonitis: diagnostics and therapeutics.
AB  - This review is concerned with what has been learned about feline infectious
      peritonitis (FIP) diagnostics and therapeutics since the publication of an
      extensive overview of literature covering the period 1963-2009. Although progress
      has been made in both areas, obtaining a definitive diagnosis of FIP remains a
      problem for those veterinarians and/or cat owners who require absolute certainty.
      This review will cover both indirect and direct diagnostic tests for the disease
      and will emphasize their limitations, as well as their specificity and
      sensitivity. There is still no effective treatment for FIP, although there are
      both claims that such therapies exist and glimmers of hope coming from new
      therapies that are under research. FIP has also been identified in wild felids
      and FIP-like disease is now a growing problem among pet ferrets.

PMID- 24857254
TI  - Verbal-motor attention-focusing instructions influence kinematics and performance
      on a golf-putting task.
AB  - The authors examined how varying the content of verbal-motor instructions and
      requesting an internal versus external focus influenced the kinematics and
      outcome of a golf putting task. On Day 1, 30 novices performed 120 trials with
      the instruction to focus attention either on performing a pendulum-like movement
      (internal) or on the desired ball path (external). After 20 retention trials on
      Day 2, they performed 20 transfer trials with the opposite instruction. Group
      differences for retention and a group by block interaction showed that external
      instruction enhanced movement outcome. Kinematic data indicated that specific
      instruction content influenced outcomes by eliciting changes in movement
      execution. Switching from the external to the internal focus instruction resulted
      in a more pendulum-like movement.

PMID- 24857255
TI  - A meta-analysis and model of the relationship between sleep and depression in
      adolescents: recommendations for future research and clinical practice.
AB  - The purpose of this review was to quantify the strength of evidence for a
      directional relationship between sleep disturbance and depression in adolescents.
      A literature search was conducted to identify research investigating the
      relationship between sleep disturbance and depression in adolescent samples (12
      20 y). Twenty-three studies were identified; 13 explored associations between
      depression and sleep disturbance; seven examined the prospective role of sleep
      disturbance in the development of depression; and three investigated the role of
      adolescent depression in the development of subsequent sleep disturbance. Average
      weighted mean differences in sleep/depression-related outcome variables were
      calculated between adolescents with depression, and non-clinical adolescents, or
      those in remission. Adolescents with depression experienced significantly more
      wakefulness in bed (sleep onset latency, wake after sleep onset, number of
      awakenings and sleep efficiency), lighter sleep (more stage 1), and reported more
      subjective sleep disturbance. Overall effect sizes from longitudinal and
      treatment studies suggest sleep disturbance acts as a precursor to the
      development of depression. At follow-up, depressed adolescents had significantly
      longer sleep onset, more wake after sleep onset, and lower sleep efficiency
      compared to adolescents who were non-clinical, or had undergone remission. Little
      support was found for a predictive role of depressive symptoms in the development
      of sleep disturbance. Based on these findings we propose a model to understand
      the development of depression from initial sleep disturbance, provide
      recommendations for clinicians and recommendations for future research.

PMID- 24857256
TI  - [Sarcopenia: a concept of growing importance in the management of colorectal
      cancer].
AB  - Malnutrition in digestive oncology affects quality of life, increases
      postoperative complication rates, and results in increased chemotherapy toxicity
      and reduced survival. Loss of skeletal muscle or sarcopenia is not correlated to
      body mass index, and might play a major role in the complications of malnutrition
      in oncology. The diagnosis of sarcopenia can be made on routinely available CT
      scanner images using consensual cutoff numbers. Lean body mass may be useful in
      normalizing the doses of hydrophilic chemotherapy drugs, such as
      fluoropyrimidines. To date, neither nutritional intervention nor specific drugs
      have proven useful in preventing or treating sarcopenia in cancer patients. 

PMID- 24857257
TI  - [Malignant insulinoma: recommendations for workup and treatment].
AB  - Insulinoma are malignant in 4 to 14 % of cases. Their rarity and the sparse data
      available in the literature have limited publication of specific guidelines for
      their management. The following review aim to provide up-to-date recommendations
      on initial evaluation including pathologic grading, measures to control
      hypoglycemia, antitumor strategies and long term follow-up. Will be discussed in
      detail respective indications of surgery, diazoxide, somatostatin analogs,
      everolimus, sunitinib, liver directed treatments including arterial embolization,
      chemotherapy and radiometabolic therapy. A Medline search using terms
      "insulinoma", "neuroendocrine pancreatic tumors", "islet cell carcinoma",
      "malignant insulinoma" was performed limiting the selection to English language
      articles and adult age cases, along with cross referencing. 

PMID- 24857258
TI  - [Anaesthetic management of patient with neurological disease: Focus on regional
      anaesthesia].
AB  - Anaesthesia of patients with neurological disease is feasible but each specific
      disease requires specific adjustments accordingly. A preoperative evaluation of
      neurological status is required and patients should be informed of the potential
      harms in the perioperative period. Regional anaesthesia is commonly considered as
      contraindicated in these patients although it is commonly not. General
      anaesthesia has not been demonstrated to worsen cognitive dysfunction in patients
      suffering from Alzheimer's disease but these dysfunctions may disturb
      postoperative rehabilitation. Regional anaesthesia has no special benefit in
      these patients. In patients with Parkinson's disease, inability to use the oral
      route in the postoperative period may impair the administration of the treatment.
      Multiple sclerosis is not a contraindication of epidural anaesthesia especially
      in obstetrics, since there is no evidence that it may trigger relapse of the
      disease especially in the postpartum period. Regional anaesthesia is doable in
      patients with a dysimmune demyelinated lesions out of the regeneration phase of
      the disease. In peripheral hereditary or acquired neuropathies regional
      anaesthesia is also feasible. Epilepsy, spina bifida and traumatic pathologies of
      the spine are not contraindications to regional anaesthesia but the latter
      require technical adjustment. 

PMID- 24857259
TI  - [Erythema multiforme due to varicella-zoster virus].

PMID- 24857260
TI  - Pathophysiology of brain injuries in acute carbon monoxide poisoning: a novel
      hypothesis.
AB  - Acute carbon monoxide (CO) poisoning causes the neurologic symptoms and brain
      lesions during both acute and delayed phase. We propose that catecholamine crises
      in globus pallidus and deep white matter are the key pathophysiological factors
      causing acute and delayed brain injuries respectively. Increased sympathetic
      activities due to acute CO poisoning is followed by increases of catecholamine
      levels in synapses or nerve terminals in organs including the brain, especially,
      limbic system. A dopamine excess in the synaptic cleft of the mesolimbic system,
      including globus pallidus, may cause the destruction of synapses and nuclei in
      the globus pallidus. Consequently, the striatal lesion is affected in the acute
      phase of CO intoxication. Moreover, an increase of catecholamine levels in
      synapses of deep white matter can persist after the acute stage of CO
      intoxication. A dopamine excess could lead to oxidative metabolism of dopamine,
      serotonergic axonal injury, or secondary myelin damage. 

PMID- 24857261
TI  - Certain attributes of the sexual ecosystem of high-risk MSM have resulted in an
      altered microbiome with an enhanced propensity to generate and transmit
      antibiotic resistance.
AB  - Surveillance data from a number of countries have indicated that antibiotic
      resistance in Neisseriagonorrhoea is strongly associated with men who have sex
      with men (MSM). This manuscript advances the hypothesis that certain features of
      the MSM sexual ecosystem may be responsible for this association. It is argued
      that in comparison with heterosexuals, high-risk MSM (hrMSM) have a higher
      prevalence of oro-penile, oro-rectal and anal sex which facilitates an enhanced
      mixing of the pharyngeal, rectal and penile microbiomes. In addition, hrMSM have
      an increased number of sexual partners per unit time and an increased prevalence
      of sexual relationships overlapping in time. The increased flux of microbiomes
      between different body habitats between sexual partners, in combination with the
      increased connectivity of the sexual network, serve to create a novel high-risk
      MSM sexual ecosystem with important consequences for the genesis and spread of
      antibiotic resistance. 

PMID- 24857262
TI  - Inter-observer reproducibility of diagnosis of diabetic foot osteomyelitis based
      on a combination of probe-to-bone test and simple radiography.
AB  - Probe-to-bone test and simple X-rays are both standard tests for the diagnosis of
      diabetic foot osteomyelitis. This study demonstrates the importance of
      considering jointly clinical information (probe-to-bone test) and diagnostic
      tests (simple radiography) to increase agreement among clinicians on diagnosis of
      diabetic foot osteomyelitis. 

PMID- 24857263
TI  - Diagnostic accuracy of glycated hemoglobin compared with oral glucose tolerance
      test for diagnosing diabetes mellitus in Chinese adults: a meta-analysis.
AB  - AIMS: A meta-analysis was conducted to evaluate the diagnostic value of glycated
      hemoglobin (HbA1c) >=6.5% (48mmol/mol) for diabetes in Chinese adults. METHODS:
      Oral glucose tolerance test (OGTT) was selected as the reference standard.
      PubMed, EMBASE, CNKI, Wanfang Data, and VIP were searched to obtain all
      diagnostic tests with HbA1c >=6.5% (48mmol/mol) for diabetes in Chinese adults
      published between January 2003 and October 2013. The qualities of the included
      studies were assessed by using the Quality Assessment of Diagnostic Accuracy
      Studies 2 tool. Meta-DiSc software was used to conduct a comprehensive
      quantitative assessment, and summary receiver operating characteristic (sROC)
      curves were obtained. RESULTS: A total of 9 studies with 25,932 subjects were
      included. Pooled sensitivity was 0.518, pooled specificity 0.956, pooled positive
      likelihood ratio 19.007 and pooled negative likelihood ratio was 0.477. Pooled
      diagnostic odds ratio was 40.631. AUCsROC was 0.929. CONCLUSION: Compared with
      OGTT, using HbA1c >=6.5% (48mmol/mol) to diagnose diabetes in Chinese adults
      exhibited high specificity and low sensitivity and would have failed to diagnose
      48.7% of newly diagnosed diabetes. The diagnostic HbA1c value could be reduced to
      improve sensitivity. Long-term prospective studies are required to establish an
      appropriate HbA1c value as a diagnostic criterion for diabetes in China.

PMID- 24857264
TI  - Repetitive transcranial magnetic stimulation (rTMS) improves facial affect
      recognition in schizophrenia.
AB  - OBJECTIVE: Facial affect recognition, a basic building block of social cognition,
      is often impaired in schizophrenia. Poor facial affect recognition is closely
      related to poor functional outcome; however, neither social cognitive impairments
      nor functional outcome are sufficiently improved by antipsychotic drug treatment
      alone. Adjunctive repetitive transcranial magnetic stimulation (rTMS) has been
      shown to enhance cognitive functioning in both healthy individuals and in people
      with neuropsychiatric disorders and to ameliorate clinical symptoms in
      psychiatric disorders, but its effects on social cognitive impairments in
      schizophrenia have not yet been studied. Therefore, we evaluated the effects of
      sham-controlled rTMS on facial affect recognition in patients with chronic
      schizophrenia. METHOD: Inpatients (N = 36) on stable antipsychotic treatment were
      randomly assigned to double-blind high-frequency (10 Hz) rTMS or sham stimulation
      for a total of ten sessions over two weeks. In the verum group, each session
      consisted of 10 000 stimuli (20 trains of 5 s) applied over the left dorsolateral
      prefrontal cortex at 110% of motor threshold. Facial affect recognition was
      assessed before (T0) and after (T1) the ten sessions. RESULTS: Facial affect
      recognition improved significantly more after rTMS (accuracy change: mean = 8.9%,
      SD = 6.0%) than after sham stimulation (mean = 1.6%, SD = 3.5; Cohen's d = 1.45).
      There was no correlation with clinical improvement. CONCLUSION: Our results
      indicate that prefrontal 10 Hz rTMS stimulation may help to ameliorate impaired
      facial affect recognition in schizophrenia.

PMID- 24857265
TI  - Predicting idiosyncratic drug-induced liver injury: some recent advances.
AB  - Drug-induced liver injury (DILI) is a major challenge for the pharmaceutical
      industry, regulatory authorities, and clinicians. It is usually categorized into
      'intrinsic' and 'idiosyncratic', but DILI caused by most drugs is of an
      idiosyncratic nature and usually cannot be predicted from the regulatory required
      animal toxicity studies. Unfortunately, some individuals exposed to therapeutic
      dose will develop idiosyncratic DILI that might involve severe clinical outcome,
      and no biomarker is available to identify the susceptible patients prior to drug
      treatment. In this editorial, we summarized the recent advances in predicting
      idiosyncratic DILI and provided the perspectives to improve the prediction. 

PMID- 24857266
TI  - Left main dissection complicating blunt chest trauma: case report and review of
      literature.
AB  - Coronary artery injury after blunt chest trauma is rare, but can be life
      threatening, resulting in severe myocardial ischaemia and acute myocardial
      infarction. We report a case of a 56-year-old male who presented a few days after
      a blunt chest trauma with crescendo unstable angina. Coronary angiography
      demonstrated left main coronary artery dissection that was fixed with stent
      implantation. After a blunt chest trauma symptoms and electrocardiographic
      findings of a coronary dissection can be nonspecific and confounded by the chest
      tenderness. In such cases careful evaluation to rule out traumatic coronary
      injuries is warranted and early intervention should not be delayed in the
      presence of clear evidence of myocardial ischemia. 

PMID- 24857267
TI  - Tunneling ultramicroelectrode: nanoelectrodes and nanoparticle collisions.
AB  - We describe the fabrication of a nanometer-size electrode based on an insulating
      TiO2 film and a metal nanoparticle (NP). The TiO2 film is deposited on the
      conducting Pt surface of an ultramicroelectrode (UME) to block electron transfer
      (ET) to solution species. The film thickness is, however, thin enough to enable
      tunneling to Pt NPs; thus, the subsequent contact of metal NP to the TiO2 film
      restores the ET to solution species solely on the NP surface via facile electron
      tunneling. Consequently, the composite of UME/metal oxide film/NP offers nm-scale
      active area. The TiO2 film is electrochemically deposited on the Pt UME (Pt
      UME/TiO2), monitoring the cyclic voltammetry (CV) of ferrocenemethanol until the
      oxidation wave just disappears. A single Pt NP is captured in a collision
      experiment by observing the current increase upon contact of the Pt NP with the
      Pt UME/TiO2 by means of Pt NP-mediated electrochemical reduction of Fe(CN)6(3-).
      The resultant Pt UME/TiO2/Pt NP (or tunneling UME, T-UME) showed long-term
      stability and robustness with well-defined electrochemical response, suggesting
      applicability as a novel nm-size electrode for CV and steady-state measurements
      such as those with scanning electrochemical microscopy (SECM). Here, we employed
      the T-UME to measure SECM approach curves and showed remarkable approach
      capability for a nm-size SECM probe. 

PMID- 24857268
TI  - Relaxation stretching, fast dynamics, and activation energy: a comparison of
      molecular and ionic liquids as revealed by depolarized light scattering.
AB  - Depolarized light scattering (DLS) spectra of a series of 16 molecular and 6 room
      temperature ionic liquids are investigated by applying tandem-Fabry-Perot
      interferometry, double monochromator, and photon correlation spectroscopy.
      Temperatures up to well above the melting point, in some cases, even up to the
      boiling point, are covered, and all liquids can be supercooled. The accessed time
      constants are between 1 ps and 10 ns; in some cases, even longer times are
      reached. The susceptibility spectra and likewise the corresponding
      reorientational correlation functions are characterized by stretching parameter
      beta(CD) (0.32-0.80) for the long-time decay (alpha-process), strength of fast
      dynamics 1 - f, and time scale at shortest times expressed by k(B)T/I* with the
      apparent quantity I* reflecting essentially inertia effects. An additional
      (intermediate) power-law regime (or excess wing in the frequency domain) between
      fast dynamics and the alpha-process has to be taken into account. For a given
      system the spectral parameters are virtually temperature independent up to the
      boiling point, i.e., frequency-temperature superposition applies for the alpha
      process. Among the liquids, the quantity I* correlates with molecular mass, and
      the larger 1 - f, the smaller the inertial quantity I*. No correlation among 1 -
      f and beta(CD) is revealed. Testing for correlation of beta(CD) or 1 - f with
      parameters describing the temperature dependence of the correlation time
      tau(alpha), namely, high-temperature activation energy E(infinity), fragility m,
      or glass transition temperature T(g), no significant correlation is found.
      Regarding molecular vs ionic liquids, no relevant difference in the evolution of
      their DLS spectra is observed.

PMID- 24857269
TI  - Reply: To PMID 24857271.

PMID- 24857270
TI  - Reply: To PMID 24857276.

PMID- 24857271
TI  - Image guidance for all--TilePro display of 3-dimensionally reconstructed images
      in robotic partial nephrectomy.
AB  - OBJECTIVE: To determine the feasibility of a novel low-barrier-to-entry image
      guidance system. METHODS: Initially a randomized crossover study was performed to
      establish the interface (iPad or 3-dimensional mouse) that minimized both the
      amount of time required to perform a manual image registration and the error of
      that registration. A subsequent clinical feasibility study was undertaken on 5
      patients undergoing robot-assisted partial nephrectomy. Randomized crossover
      study primary outcomes were time to task completion, NASA-Task Load Index score,
      and alignment error (translational and rotational). The Mann-Whitney U test was
      used to compare groups. Surgeon feedback was sought when assessing the system in
      a clinical setting. RESULTS: In the initial randomized crossover study, the iPad
      based system was able to achieve adequate alignment accuracy (Frobenius norm of
      0.3; total error of 20.8 mm) in significantly less time (33 seconds; P<.01) than
      the 3-dimensional mouse interface. The platform received good feedback from the
      operating surgeon in all instances with the surgeon commenting particularly on
      the improved appreciation of hilar vascular anatomy. CONCLUSION: In this study,
      we have demonstrated the feasibility of a "low-barrier-to-entry" image guidance
      system in a clinical setting. The system was able to achieve swift and
      sufficiently accurate alignment, with little impact on the surgical workflow.

PMID- 24857272
TI  - The effectiveness of 4.5F ultrathin semirigid ureteroscope in the management of
      ureteral stones in prepubertal children: is there a need for any ureteral
      dilatation?
AB  - OBJECTIVE: To evaluate the effectiveness of 4.5F ultrathin semirigid ureteroscope
      (ultrathin-URS) in the management of ureteral stones in prepubertal children
      without active or passive ureteral dilatation. MATERIALS AND METHODS: Records of
      36 children undergoing ureteroscopy with ultrathin-URS were retrospectively
      reviewed in 2 different centers for ureteral calculi between November 2011 and
      December 2013. Stones were fragmented with holmium:yttrium-aluminum-garnet laser
      and pneumatic lithotripter. Patients' demographics, stone location and size,
      active dilatation, passive dilatation, postoperative stenting, stone-free rates,
      and complications were noted. RESULTS: Patients consisted of 21 girls and 15 boys
      with a mean age of 5.33+/-3 years. Stones were located in the distal, mid, and
      proximal ureter in 26, 5, and 5 patients, respectively. All ureteroscopies were
      performed with no active or passive dilatation. Ultrathin-URS was able to provide
      a stone-free status in the first procedure except 1 patient whose stone was too
      proximal. Postoperative ureteral stents (post-stenting) had initially been placed
      in 16 procedures at the end of the procedure to maintain the ureteral passage.
      However, after increasing occupational experience and learning that ureteral
      traumas were minimal with ultrathin-URS, no postoperative stent was used in the
      following procedures. As to complications, only 3 patients had mild hematuria,
      and 1 patient had febrile urinary tract infection, and 1 stone migration. No
      ureteral perforation, obstruction and avulsion were encountered. CONCLUSION: In
      ureteral stone management, ultrathin-URS along with either holmium:yttrium
      aluminum-garnet laser or pneumatic lithotripter can be safely and effectively
      used with a minimal morbidity as a first-line treatment in prepubertal children
      without active or passive ureteral dilatation and postoperative stenting.

PMID- 24857273
TI  - Editorial comment.

PMID- 24857274
TI  - Perineal lipoma with accessory labioscrotal fold and penis-like phallus in a
      female infant with unilateral renal agenesis.
AB  - We present a case of a female 46,XX infant with a perineal lipoma within an
      accessory labioscrotal fold containing a penis-like phallus, associated with
      contralateral renal agenesis and complete absence of Mullerian/paramesonephric
      structures. To our knowledge, this is the first report of perineal lipoma and
      accessory labioscrotal fold associated with urogenital abnormalities in a female.
      The case also has an exceptional penis-like phallus in the absence of Y
      chromosome material or evidence of virilization. 

PMID- 24857275
TI  - Prognostic significance of lactate/proton symporters MCT1, MCT4, and their
      chaperone CD147 expressions in urothelial carcinoma of the bladder.
AB  - OBJECTIVE: To investigate the prognostic significance of lactate/proton
      monocarboxylate transporters MCT1, MCT4, and their chaperone CD147 expressions in
      urothelial carcinoma of the bladder (UCB). METHODS: We examined the expressions
      of MCT1, MCT4, and CD147 proteins in a total of 360 cases of UCB by
      immunohistochemistry. The immunohistochemical expressions were quantified using
      an ImageJ-based analysis program. RESULTS: MCT1, MCT4, and CD147 expressions were
      increased in 130 (36.1%), 168 (46.7%), and 228 (63.3%) UCB cases, respectively.
      Most tumor cells showed diffuse membranous staining, whereas normal urothelial
      cells showed negative or weak staining. High levels of MCT1 expression correlated
      with high World Health Organization grade (P<.001), advanced tumor node
      metastasis (TNM) stage (P<.001), nonpapillary growth type (P<.001), and lymphatic
      tumor invasion (P=.010), whereas high levels of MCT4 expression did not
      significantly correlate with any of these variables. High CD147 expression was
      associated with high World Health Organization grade (P<.001), advanced tumor
      node metastatis stage (P<.001), and nonpapillary growth type (P=.003). Univariate
      analyses revealed that high MCT1 (P<.001) and CD147 (P=.029) expressions were
      associated with poor overall survival and that high MCT4 expression was
      correlated with poor recurrence-free survival (P=.036). Multivariate analyses
      revealed that high MCT1 and MCT4 expressions were independent prognostic factors
      for poor overall survival and poor recurrence-free survival, respectively, in UCB
      patients. CONCLUSION: Our results indicate that increased MCT1, MCT4, and CD147
      expressions have prognostic implications in UCB and suggest their roles in
      urothelial cancer metabolism.

PMID- 24857276
TI  - Editorial comment.

PMID- 24857277
TI  - Wilms tumor: a retrospective study of 32 patients using videolaparoscopic and
      open approaches.
AB  - OBJECTIVE: To compare videolaparoscopic nephrectomy and the open technique as
      treatments for Wilms tumor, specifically the surgical results, immediate and long
      term complications, and patient survival. METHODS: A review of charts of children
      with unilateral Wilms tumor was performed. There were 2 surgical groups: (1) only
      open surgery and (2) videolaparoscopy. Complications, transfusion, ruptures,
      margins, conversions, lymph nodes, and relapse were analyzed. RESULTS: Seventeen
      children underwent laparoscopic nephrectomy and 15 underwent open nephrectomy.
      Mean surgical time was 164.71+/-26.07 minutes for the laparoscopic group, and
      there were no conversions or ruptures. The mean specimen weight was 145.01+/
      105.85 g for the laparoscopic group and 257.40+/-162.70 g for the open surgery
      group. There was 1 preoperative rupture in the open surgery group. Transfusions
      were not required in either group. The surgical margins were positive in 1 of 17
      cases (5.9%) in the laparoscopic group and in 3 of 15 cases (20%) in the open
      surgery group. One of the 17 (5.9%) laparoscopy-treated patients and 2 of the 15
      open surgery-treated patients (13.3%) presented with local tumor relapse. The 5
      year event-free survival rate was 93.3% (95% confidence interval, 0.61-0.99) for
      the laparoscopic group and 79.6% (95% confidence interval, 0.37-0.95] for the
      open surgery group (P=.446). CONCLUSION: Both techniques showed similar immediate
      and long-term results.

PMID- 24857278
TI  - Iatrogenic nonendoscopic bladder injuries over 24 years: 127 cases at a single
      institution.
AB  - OBJECTIVE: To analyze the etiology, diagnosis, and long-term outcomes of
      iatrogenic nonendoscopic bladder injuries over a 24-year period. METHODS: All
      iatrogenic bladder injuries were entered prospectively into our database from
      1990 to 2014. Information gathered included causative procedure, injury
      characteristics, management, and outcome. RESULTS: A total of 127 patients with
      nonendoscopic iatrogenic bladder injuries were included (111 women [87%], 16 men
      [13%]; mean age 51 years [range, 23-84]). Risk factors were identified in 92
      patients (79%) including prior surgery, inflammation, and extensive tumor.
      Obstetric-gynecologic surgery accounted for most injuries (65%), with
      hysterectomy the most common procedure, followed by cesarean section. General
      surgery and nonendoscopic urologic injuries accounted for 22% and 13%
      respectively. Most injuries occurred during open surgery (77%) compared with
      vaginal (12%) and laparoscopic surgeries (11%). Laparoscopic surgery was
      associated with a delay in diagnosis, P=.002. Bladder injuries with concomitant
      ureteral injuries were more likely to have long-term complications, P=.001.
      CONCLUSION: In analyzing iatrogenic bladder injuries at our institution over 24
      years, we observed that hysterectomy and cesarean sections were the 2 most common
      causative procedures. A delay in diagnosis was more likely to occur during
      laparoscopic surgery. Complications occurred more commonly with a concomitant
      ureteral injury.

PMID- 24857279
TI  - Optimal beam design on intensity-modulated radiation therapy with simultaneous
      integrated boost in nasopharyngeal cancer.
AB  - This study aims to determine the optimal beam design among various combinations
      of field numbers and beam trajectories for intensity-modulated radiation therapy
      (IMRT) with simultaneous integrated boost (SIB) technique for the treatment of
      nasopharyngeal cancer (NPC). We used 10 fields with gantry angles of 155 degrees
      , 130 degrees , 75 degrees , 25 degrees , 0 degrees  L, 0 degrees  R, 335 degrees
      , 285 degrees , 230 degrees , and 205 degrees  denoted as F10. To decrease doses
      in the spinal cord, the F10 technique was designed by featuring 2 pairs of split
      opposed beam fields at 155 degrees  to 335 degrees  and 205 degrees  to 25
      degrees , as well as one pair of manually split beam fields at 0 degrees . The
      F10 technique was compared with 4 other common field arrangements: F7E, 7 fields
      with 50 degrees  equally spaced gantry angles; F7, the basis of F10 with 155
      degrees , 130 degrees , 75 degrees , 0 degrees , 285 degrees , 230 degrees , and
      205 degrees ; F9E, 9 fields with 40 degrees  equally spaced gantry angles; and
      FP, 7 posterior fields with 180 degrees , 150 degrees , 120 degrees , 90 degrees
      , 270 degrees , 240 degrees , and 210 degrees . For each individual case of 10
      patients, the customized constraints derived after optimization with the standard
      F10 technique were applied to 4 other field arrangements. The 4 new optimized
      plans of each individual case were normalized to achieve the same coverage of
      planning target volume (PTV)63Gy as that of the standard F10 technique. The F10
      field arrangement exhibited the best coverage in PTV70Gy and the least mean dose
      in the trachea-esophagus region. Furthermore, the F10 field arrangement
      demonstrated the highest level of conformity in the low-dose region and the least
      monitor unit. The F10 field arrangement performed more outstandingly than the
      other field arrangements in PTV70Gy coverage and spared the central organ. This
      arrangement also exhibited the highest conformity and delivery efficiency. The
      F10 technique is recommended as the standard beam geometry for the SIB-IMRT of
      NPC. 

PMID- 24857280
TI  - Isotonic saline nasal irrigation is an effective adjunctive therapy to intranasal
      corticosteroid spray in allergic rhinitis.
AB  - BACKGROUND: This study was designed to determine if the addition of large-volume,
      low-positive pressure nasal irrigations delivered with isotonic sodium chloride
      (hereinafter "saline") added to intranasal corticosteroid therapy improves
      quality of life and objective measures of nasal breathing in patients with
      allergic rhinitis when compared with intranasal corticosteroid alone. METHODS: A
      prospective, unblinded, single-arm pilot study was performed of patients with
      allergic rhinitis already on intranasal corticosteroid pharmacotherapy. Patients
      added large-volume low-pressure saline irrigation twice daily for 8 weeks to
      their ongoing regiment of nasal corticosteroid. Mini-Rhinoconjunctivitis Quality
      of life Questionnaire (mRQLQ) assessment and nasal peak inspiratory flow (NPIF)
      were performed at baseline and at 4 and 8 weeks. RESULTS: A total of 40 patients
      were enrolled. Twice-daily nasal irrigation with isotonic saline significantly (p
      < 0.001) reduced mRQLQ scores, from 36.7 +/- 20.48 (baseline) to 14.9 +/- 11.03
      (4 weeks) to 10.10 +/- 10.65 (8 weeks). No significant changes were seen in NPIF,
      pattern use of nasal steroid use, or adverse events. CONCLUSION: Large-volume,
      low-positive pressure nasal irrigation with isotonic saline is an effective
      adjunctive therapy to improve quality of life in patients with allergic rhinitis
      already on intranasal corticosteroid therapy. This study was a part of the
      clinical trial NCT01030146 registered at clinicaltrials.gov.

PMID- 24857283
TI  - Effect of alcohol in traumatic brain injury: is it really protective?
AB  - BACKGROUND: Studies have proposed a neuroprotective role for alcohol (ETOH) in
      traumatic brain injury (TBI). We hypothesized that ETOH intoxication is
      associated with mortality in patients with severe TBI. METHODS: Version 7.2 of
      the National Trauma Data Bank (2007-2010) was queried for all patients with
      isolated blunt severe TBI (Head Abbreviated Injury Score >=4) and blood ETOH
      levels recorded on admission. Primary outcome measure was mortality. Multivariate
      logistic regression analysis was performed to assess factors predicting mortality
      and in-hospital complications. RESULTS: A total of 23,983 patients with severe
      TBI were evaluated of which 22.8% (n = 5461) patients tested positive for ETOH
      intoxication. ETOH-positive patients were more likely to have in-hospital
      complications (P = 0.001) and have a higher mortality rate (P = 0.01). ETOH
      intoxication was an independent predictor for mortality (odds ratio: 1.2, 95%
      confidence interval: 1.1-2.1, P = 0.01) and development of in-hospital
      complications (odds ratio: 1.3, 95% confidence interval: 1.1-2.8, P = 0.009) in
      patients with isolated severe TBI. CONCLUSIONS: ETOH intoxication is an
      independent predictor for mortality in patients with severe TBI patients and is
      associated with higher complication rates. Our results from the National Trauma
      Data Standards differ from those previously reported. The proposed
      neuroprotective role of ETOH needs further clarification.

PMID- 24857284
TI  - Risk factors, prevalence trend, and clustering of hypospadias cases in Puerto
      Rico.
AB  - OBJECTIVE: The aim was to determine the distribution pattern of hypospadias cases
      across a well-defined geographic space. MATERIALS AND METHODS: The dataset for
      this study was produced by the Birth Defects Prevention and Surveillance System
      of the Department of Health of Puerto Rico (BDSS-PR), which linked the
      information of male newborns of the Puerto Rico Birth Cohort dataset (PRBC;
      n=92,285) from 2007 to 2010. A population-based case-control study was conducted
      to determine prevalence trend and to estimate the potential effects of maternal
      age, paternal age, birth-related variables, and health insurance status on
      hypospadias. Two types of geographic information systems (GIS) methods (Anselin
      Local Moran's I and Getis-Ord G) were used to determine the spatial distribution
      of hypospadias prevalence. RESULTS: Birthweight (<2500 g), age of mother
      (40+years), and private health insurance were associated with hypospadias as
      confirmed with univariate and multivariate analyses at 95% CI. A cluster of
      hypospadias cases was detected in the north-central region of Puerto Rico with
      both GIS methods (p<=0.05). CONCLUSIONS: The clustering of hypospadias prevalence
      provides an opportunity to assess the underlying causes of the condition and
      their relationships with geographical space.

PMID- 24857285
TI  - Re. 'BAPU consensus statement on the management of the primary obstructive
      megaureter'.

PMID- 24857286
TI  - In vitro and in vivo approaches to characterize transporter-mediated disposition
      in drug discovery.
AB  - INTRODUCTION: It is becoming increasingly evident that transporters play an
      important role in the absorption, distribution and elimination of many drugs.
      Different approaches have been developed and validated to understand the
      interactions between drugs and transporters, and the in vivo role of drug
      transporters. These tools are helping to understand the impact of transporters on
      the pharmacokinetics (PK) of drugs and assess the risk of drug-drug interactions
      (DDIs) in drug discovery and development. AREAS COVERED: This article provides an
      overview of different approaches to evaluate the drug transporters involved in
      intestinal absorption, hepatic and renal clearance, and brain penetration.
      Specifically, it provides the best practices to evaluate the major uptake and
      efflux transporters in drug discovery. It also discusses the challenges and gaps
      in understanding the clinical relevance of drug transporters. EXPERT OPINION:
      Quantitative prediction of transporter-mediated clearance, tissue exposure, as
      well as DDIs is still limited. The current challenge is to develop in vitro-in
      vivo correlations, extrapolate and integrate data from in vitro transporter
      assays, and preclinical species into humans to quantitatively predict the impact
      of transporters on drug absorption, disposition, elimination and DDIs. With the
      development of a variety of novel tools, the ultimate goal is to use high quality
      in vitro and in vivo data to establish physiologically based PK models, which
      will improve the capability to predict PK, tissue exposure and DDIs in humans.

PMID- 24857290
TI  - Synthesis of some novel phosphorylated and thiophosphorylated benzimidazoles and
      benzothiazoles and their evaluation for larvicidal potential to Aedes albopictus
      and Culex quinquefasciatus.
AB  - Series of benzimidazole and benzothiazole linked phosphoramidates and
      phosphoramidothioates (5a-j) and benzimidazole linked phenylphosphoramidates and
      phenylphosphoramidothioates (10a-e) were synthesized. The title compounds were
      preliminary screened for mosquito larvicidal properties against Aedes albopictus
      and Culex quinquefasciatus at different concentration from 40 to 5 mg/L. Among
      the screened compounds three compounds revealed potential larvicidal effects with
      100% mortality in the order of 10e>5j>5e. Compound 10e was found to be the most
      toxic compound to Ae. albopictus and Cx. quinquefasciatus. The LC50 of 10e
      against Ae. albopictus was found to be 6.42 and 5.25 mg/L at 24 and 48 h,
      respectively, whereas it was 7.01 and 3.88 mg/L, respectively in Cx.
      quinquefasciatus. Temephos was used as positive control.

PMID- 24857291
TI  - Cell-SELEX-based selection of aptamers that recognize distinct targets on
      metastatic colorectal cancer cells.
AB  - The development of diagnostic/therapeutic strategies against metastasis-related
      molecular targets is critical for improving the survival rate of cancer patients.
      Subtractive Cell-SELEX was performed using highly metastatic colorectal cancer
      (CRC) LoVo cells and non-metastatic HCT-8 cells as the target and negative cells,
      respectively, for the selection of metastatic-specific aptamers. This process
      generated seven aptamers that displayed highly specific binding to the target
      cells with Kds in the nanomolar range. Based on the distinct chemical/biological
      properties of their individual cell surface targets, the aptamers were separately
      functionalized: the receptor-targeting aptamer W14 was used as a carrier for
      doxorubicin, resulting in the specific delivery of the drug to the target cells
      and a significant reduction of its cytotoxicity to non-target cells, and the non
      receptor-binding aptamer W3 was used as a molecular probe conjugated to quantum
      dots for the targeted imaging of metastatic cancer cell lines, spontaneous lung
      metastasis murine tissue, and metastatic CRC patient tissues. In addition, these
      aptamers can be used in combination due to their lack of detectable mutual
      binding interference. The study demonstrates that a panel of aptamers that
      recognize distinct features of target molecules can be obtained through single
      Cell-SELEX selection, and the selected aptamers may be individually
      functionalized for specific applications and/or utilized in combination. 

PMID- 24857292
TI  - Manipulating hepatocellular carcinoma cell fate in orthogonally cross-linked
      hydrogels.
AB  - De-differentiation and loss of function in hepatocytes during two-dimensional
      (2D) tissue culture significantly hinders the progress of liver research. An
      ideal three-dimensional (3D) in vitro liver parenchymal cell culture platform
      should restore cell-cell and cell-matrix interactions, as well as normal
      hepatocyte polarity. Here, we report an orthogonal thiol-ene hydrogel system for
      culturing liver cell lines (e.g. Huh7 and HepG2). The hydrogels were prepared by
      a radical-mediated orthogonal thiol-norbornene photo-click chemistry using
      poly(ethylene glycol)-tetra-norbornene (PEG4NB) macromer and di-thiol containing
      linker (e.g., dithiothreitol (DTT) or bis-cysteine matrix metalloproteinase (MMP)
      sensitive peptide). This system also allows facile incorporation of bioactive
      peptides (e.g., fibronectin-derived RGDS) to improve cell-matrix interactions.
      Encapsulated Huh7 and HepG2 cells showed elevated urea secretion and CYP3A4
      enzymatic activities, as well as up-regulated mRNA levels of multiple hepatocyte
      genes (e.g., CYP3A4, BESP, and NTCP). Importantly, this is the first 3D hydrogel
      system that up-regulates the expression of NCTP in encapsulated Huh7 and HepG2
      cell lines without any genetic modification or the addition of growth factors and
      chemical additives. Furthermore, the encapsulated cells displayed hepatocyte-like
      polarity distinctively different from the polarity displayed in 2D culture. These
      characteristics not only allow the study of hepatology in 3D using inexpensive
      cell lines, but also permit large-scale small-molecule screening. The up
      regulation of NTCP expression and restoration of hepatocyte-like polarity in our
      hydrogels also shed light on future study of hepatitis B virus infection in
      vitro.

PMID- 24857293
TI  - Impact of the initial classic section during a simulated cross-country skiing
      skiathlon on the cardiopulmonary responses during the subsequent period of skate
      skiing.
AB  - The aim of this study was to assess potential changes in the performance and
      cardiorespiratory responses of elite cross-country skiers following transition
      from the classic (CL) to the skating (SK) technique during a simulated skiathlon.
      Eight elite male skiers performed two 6 km (2 * 3 km) roller-skiing time trials
      on a treadmill at racing speed: one starting with the classic and switching to
      the skating technique (CL1-SK2) and another employing the skating technique
      throughout (SK1-SK2), with continuous monitoring of gas exchanges, heart rates,
      and kinematics (video). The overall performance times in the CL1-SK2 (21:12 +/-
      1:24) and SK1-SK2 (20:48 +/- 2:00) trials were similar, and during the second
      section of each performance times and overall cardiopulmonary responses were also
      comparable. However, in comparison with SK1-SK2, the CL1-SK2 trial involved
      significantly higher increases in minute ventilation (VE, 89.8 +/- 26.8 vs. 106.8
      +/- 17.6 L.min(-1)) and oxygen uptake (VO2; 3.1 +/- 0.8 vs 3.5 +/- 0.5 L.min(-1))
      2 min after the transition as well as longer time constants for VE, VO2, and
      heart rate during the first 3 min after the transition. This higher
      cardiopulmonary exertion was associated with ~3% faster cycle rates. In
      conclusion, overall performance during the 2 time trials did not differ. The
      similar performance times during the second sections were achieved with
      comparable mean cardiopulmonary responses. However, the observation that during
      the initial 3-min post-transition following classic skiing cardiopulmonary
      responses and cycle rates were slightly higher supports the conclusion that an
      initial section of classic skiing exerts an impact on performance during a
      subsequent section of skate skiing. 

PMID- 24857294
TI  - [Some thoughts on the prevention and control of dyslipidemia and atherosclerotic
      cardiovascular disease in China].

PMID- 24857295
TI  - [The interpretation of 2014 evidence-based guidelines for the management of high
      blood pressure in adults].

PMID- 24857296
TI  - [The common problems and available solutions of design of clinical research].

PMID- 24857297
TI  - [Prediction models for the 15 years risk of new-onset hypertension in Chinese
      people aged from 35 to 64 years old].
AB  - OBJECTIVE: To set up prediction models for the risk of new-onset hypertension in
      Chinese people and explore the risk scores to facilitate the clinical
      application. METHODS: A cohort set up since 1992 with participants aged 35-64
      years old from 11 provinces and cities of China was prospectively studied.
      Logistic regression was used to analyze the risk factors for the incidence of
      hypertension within 15 years and the prediction models and risk scores were
      developed with the regression coefficient. The performance of the prediction
      models were tested and compared with the Framingham model. RESULTS: A total of 3
      899 participants free from hypertension at baseline with 15 years follow-up were
      enrolled in the study. Within 15 years, 1 776 cases of incident hypertension were
      ascertained with a incidence rate of 45.6%. Two prediction models were set up
      with age, systolic blood pressure, diastolic blood pressure, BMI and the history
      of parental hypertension in the Model 1, while TG and HDL-C added on the basis of
      Model 1 in the Model 2. Good performance of discrimination and calibration was
      established in both models with significant difference in C statistics and no
      significant difference in net reclassification improvement (NRI) index.
      CONCLUSION: The hypertension risk prediction models can be used to estimate an
      individual's absolute risk for hypertension and could facilitate the management
      of potential hypertension patients.

PMID- 24857298
TI  - [An analysis of risk factors for stroke in atrial fibrillation and hypertension
      patients].
AB  - OBJECTIVE: To explore the independent risk factors for the 1 year stroke event in
      Chinese patients with atrial fibrillation (AF) and hypertension (HT). METHODS:
      Data of AF and HT patients in the Chinese Emergency Atrial Fibrillation Registry
      Study were retrospectively analyzed. The eligible patients were divided into the
      stroke group and the non-stroke group according to the result of 1 year follow
      up. The predictors for the 1 year stroke event were identified by uni- and multi
      variate Cox regression analysis with the baseline and therapeutic variables.
      RESULTS: A total of 1 118 AF and HT patients were enrolled in the study with the
      incidence of 1 year stroke event of 8.7%. All patients were divided into the
      stroke group (n = 97) and the non-stroke group (n = 1 021). Compared with the non
      stroke group, more female patients were in the stroke group (68.0% vs 54.5%, P <
      0.05) and the patients in the stroke group were older [(76.0 +/- 9.4) years vs
      (71.9 +/- 10.6) years, P < 0.01] with higher proportion of previous history of
      stroke (38.1% vs 23.8%, P < 0.01). More patients were observed on the
      antihypertensive treatment in the non-stroke group (91.6% vs 85.6%, P < 0.05),
      while more patients on statins in the stroke group (45.4% vs 34.5%, P < 0.05).
      Multi-variate Cox regression analysis showed that age (HR = 1.036, 95%CI 1.010
      1.062), female (HR = 1.908, 95%CI 1.170-3.110), previous stroke history (HR =
      1.680, 95%CI 1.084-2.603), and no antihypertensive treatment (HR = 1.955, 95%CI
      1.008-3.791) were independent risk factors for the 1 year stroke event in
      patients with AF and HT. CONCLUSION: Age, female, previous stroke history and no
      antihypertensive treatment are the independent risk factors for the 1 year stroke
      event in patients with AF and HT.

PMID- 24857299
TI  - [Short- or long-outcome of early tirofiban in ST-segment elevated acute
      myocardial infarction undergoing elective percutaneous coronary intervention].
AB  - OBJECTIVE: To explore the optimal timing of tirofiban early treatment in ST
      segment elevated acute myocardial infarction (STEMI) undergoing elective
      percutaneous coronary intervention (PCI). METHODS: A total of 118 consecutive
      STEMI patients were enrolled in the study. They were randomly assigned to the
      tirofiban early treatment group with tirofiban administrated routinely at >= 4
      hours prior to angiography or the control group with tirofiban provisional
      administrated during or after angiography. Thrombolysis in myocardial infarction
      (TIMI) flow, creatine kinase MB isoenzyme (CK-MB) levels, acute thrombus events,
      efficacy and safety endpoints at Day 7, Day 30, 6 months and 1 year (efficacy
      endpoints: death, myocardial infarction, target vessel revascularization and
      ischemic stroke; safety endpoints: bleeding and thrombocytopenia) were observed
      and compared between the two groups. RESULTS: A total of 104 STEMI patients
      underwent elective PCI with 52 patients in each group and the baseline
      characteristics were balanced between the two groups. Tirofiban was administered
      (5.9 +/- 2.9) hours earlier in the tirofiban early treatment group than the
      control group. No statistical difference was observed between the two groups in
      TIMI flow before[grade 0: 18 (34.6%) vs 19 (36.5%) , grade 3: 28 (53.8%) vs 27
      (51.9%)] and after PCI[grade 3: 52 (100.0%) vs 51 (98.1%)]. No difference was
      shown between the two groups in CK-MB levels before PCI [(12.9 +/- 5.1) U/L vs
      (12.0 +/- 5.2) U/L, P > 0.05]; and the increase of CK-MB 12-24 hours after PCI
      [(1.0 +/- 6.2) U/L vs (2.3 +/- 8.3) U/L, P > 0.05]. The incidence of acute
      thrombus events was similar (7.7% vs 15.4%, P > 0.05). No statistical difference
      was observed between the two groups in the efficacy endpoints at Day 7 (0.0% vs
      7.7%, P > 0.05), Day 30 (0.0% vs 7.8%, P > 0.05), 6 months (2.0% vs 9.8%, P >
      0.05) and 1 year (2.2% vs 9.8%, P > 0.05). Similar incidence was shown in the
      slight bleeding (15.4% vs 5.8%, P > 0.05) and the slight thrombocytopenia (0.0%
      vs 1.9%, P > 0.05), while no severe to moderate bleeding or severe
      thrombocytopenia happened in both groups. CONCLUSION: Tirofiban early treatment
      is not better than the tirofiban bailout treatment during or after PCI in STEMI
      patients undergoing elective PCI. Trail registration ChiCTR-TRC-10000809.

PMID- 24857300
TI  - [The association of duration of hypertension and changes in cognitive function in
      hypertension patients].
AB  - OBJECTIVE: To investigate the relationship between duration of hypertension and
      cognitive function in adult hypertension patients. METHODS: A total of 224
      subjects with normal blood pressure were enrolled in group A, and 1 296 patients
      with poorly controlled hypertension were further divided by the duration of
      hypertension into group B ( <= 5 years), group C (6-10 years), group D (11-20
      years) and group E (> 20 years). Face-to-face surveys were conducted in all the
      subjects by trained physicians using Mini-Mental-State-Examination (MMSE) and
      Clock-Drawing-Test (CDT). The incidences of cognitive impairment were compared
      among the five groups and the relationship between duration of hypertension and
      cognitive function were analyzed by SPSS 18.0 software. RESULTS: (1)Compared with
      the normotensive group, the hypertensive group performed worse in the scores of
      MMSE, CDTs, the memory type cognitive function and the non-memory type cognitive
      function (MMSE:Z = -2.585, P = 0.010; CDTs:Z = -3.689, P < 0.001; memory type
      cognitive function:Z = -2.718, P = 0.007; non-memory type cognitive function: Z =
      -1.994, P = 0.046). (2) The incidences of cognitive impairment in the five groups
      were 3.6% (8/224), 6.6% (26/393), 16.6% (72/433), 19.7% (55/279) and 33.5%
      (64/191), respectively. (3) Compared with the group A, the cognitive function was
      significantly worse in the group E (MMSE:Z = 61.314, P < 0.001; CDTs: Z = 44.642,
      P < 0.001; memory type cognitive function:Z = 35.703, P < 0.001; non-memory type
      cognitive function:Z = 54.440, P < 0.001). CONCLUSIONS: Hypertension is a risk
      factor for the cognitive dysfunction. The incidence of cognitive dysfunction and
      the severity are positively associated with the duration of hypertension. In
      those with hypertension over 20 years, the cognitive dysfunction occurs much more
      obviously.

PMID- 24857301
TI  - [Evaluation of serum creatinine level in amyotrophic lateral sclerosis patients].
AB  - OBJECTIVE: To investigate the serum creatinine (SCr) level in patients with
      sporadic amyotrophic lateral sclerosis (sALS) and to explore the relationship
      between the SCr level and the clinical characteristics. METHODS: A total of 80
      patients with sALS, 80 patients with multiple system atrophy (MSA) and 80
      patients with tension-type headache (TTH) were enrolled in the study. The SCr
      levels were compared among the three groups. The association between the SCr
      level and the revised Amyotrophic Lateral Sclerosis Functional Rating Scale
      (ALSFRS-R), the forced vital capacity (FVC) percentage of predicted (FVC%pred),
      the site of symptom onset, the duration of disease and the rate of disease
      progression was evaluated in the sALS group. RESULTS: The SCr level was
      significantly decreased in the sALS group than the other two groups [(60.86 +/-
      16.80) umol/L vs (70.05 +/- 12.79) umol/L and (66.97 +/- 14.14) umol/L, P <
      0.01].In the sALS group, the SCr level was positively correlated with the ALSFRS
      R (r = 0.315, P = 0.005), while no correlation was found between the SCr level
      and the FVC%pred, the site of symptom onset, the duration of disease and the rate
      of disease progression (all P > 0.05). CONCLUSION: The SCr level is an important
      biochemical index in the patients with sALS and might play an important role in
      monitoring the disease progression.

PMID- 24857302
TI  - [Gender-related clinical characteristics in patients with differentiated thyroid
      cancers].
AB  - OBJECTIVE: To investigate the clinical characteristics of patients with different
      gender who diagnosed as differentiated thyroid cancers (DTC). METHODS: A cohort
      of patients with DTC underwent surgery in Chinese PLA General Hospital from
      October 2001 to may 2011 was retrospectively studied. RESULTS: (1) A total of 1
      756 patients with DTC were enrolled in the study and a marked female
      preponderance was found with the female/male ratio of 2.32: 1. The peak incidence
      was 35-45 years old in both genders.Higher prevalence of DTC was observed in the
      male patients with a single nodule than in the males with multinodulars (36.42%
      vs 28.90%, P < 0.01), while no statistical difference was found in the female
      patients (33.60% vs 31.77%, P > 0.05). (2) Ultrasound examination revealed that,
      the female DTC patients with microcalcification thyroid nodules were more than
      the male patients (69.26% vs 62.62%, P < 0.05), while less in female patients
      with undefined boundary thyroid nodules (57.79% vs 72.01%, P < 0.01). The tumor
      size was shown to be smaller in the women than in the men [(1.6 +/- 1.3) cm vs
      (1.8 +/- 1.5) cm, P < 0.01]. (3) Higher rates of III/IV TNM Stage, lymph node
      metastasis and extrathyroidal invasion were found in the men than in the women
      (21.74% vs 14.51%, P < 0.01, 33.27% vs 23.80%, P < 0.01 and 10.59% vs 7.17%, P <
      0.01). CONCLUSION: There is significant gender-related difference of clinical
      characteristics in the patients with DTC.

PMID- 24857303
TI  - [Familial adenomatous polyposis:a report of 10 cases in 3 generations of a family
      and literature review].
AB  - OBJECTIVE: To investigate the clinical characteristic, diagnosis and treatment of
      familial adenomatous polyposis (FAP). METHODS: According to family history of the
      proband, we surveyed the pedigree and retrospectively analyzed the clinical
      characteristics of 10 FAP patients in 3 generations of the family. RESULT: Among
      all 10 cases, 3 died of colorectal cancer including two of whom had history of
      intestinal obstruction.Seven people of the third generation were all diagnosed as
      FAP. Among them, only 2 patients had clinical symptoms. Colonoscopy was done in
      all 7 patients before 35 years old. However, none of them had polyps or evidence
      of cancer.Surgical operation was performed on 1 patient and high frequency
      electric cutting under endoscopy was performed on 6 patients. CONCLUSIONS: The
      early clinical manifestations of FAP are nonspecific. Pedigree investigation and
      colonoscopy screening for high-risk population are important to find early
      asymptomatic FAP patients.

PMID- 24857304
TI  - [The effect of body temperature control on organ function and prognosis in
      patients with refractory septic shock].
AB  - OBJECTIVE: To investigate the effect of body temperature control on organ
      function and prognosis in patients with refractory septic shock. METHODS: A total
      of 67 eligible patients with the body temperature over 38.5  degrees C were
      enrolled in the study and all patients were treated with a water-flow cooling
      blanket to control the body temperature below 38.3  degrees C for 72 hours. The
      core and peripheral temperature was tested at 1 hour interval. All patients were
      devised into the following two groups according to their mean core temperature
      within the 72 hours: the HT group with a mean core temperature >= 37.5  degrees C
      and the LT group with a mean core temperature <37.5  degrees C. Hemodynamic,
      respiratory, and laboratory parameters were tested every 6 hours during the first
      72 hours after the temperature increased above 38.5  degrees C. RESULTS: Thirty
      four patients (50.7%) were classified into the HT group, while thirty-three
      patients (49.3%) were in the LT group. Compared with the HT group, higher
      mortality rate at Day 28 was observed in the LT group (69.7% vs 35.3%, P =
      0.005). Significant difference in the increase of sepsis-related organ failure
      assessment (SOFA) score was found between of the HT and the LT groups (1.30 +/-
      0.90 vs 2.30 +/- 2.10, P = 0.02). Statistical differences were observed between
      the two groups in mean core temperature [(37.90 +/- 0.30)  degrees C vs (36.80 +/
      0.60)  degrees C, P < 0.000 1], mean peripheral temperature [(37.20 +/- 0.30) 
      degrees C vs (36.30 +/- 0.60)  degrees C, P < 0.000 1], minimum core temperature
      [(36.90 +/- 0.30) degrees C vs (35.80 +/- 0.60)  degrees C, P < 0.000 1] and
      minimum peripheral temperature [(36.20 +/- 0.40)  degrees C vs (35.50 +/- 0.60) 
      degrees C, P < 0.000 1], but not in maximum core and peripheral
      temperature.Statistical difference was also shown in troponin I, fibrinogen,
      partial thromboplastin and activated partial thromboplastin between the two
      groups. Cox regression analysis revealed that the mean core temperature was the
      only independent predictor for the mortality rate at Day 28. CONCLUSION: Body
      temperature control within the normal range may exert potentially detrimental
      effect on organ function and prognosis in patients with refractory septic shock
      with fever.

PMID- 24857305
TI  - [An analysis of etiologies of fever of unknown origin in 372 patients].
AB  - OBJECTIVE: To analyze the etiology of fever of unknown origin (FUO). METHODS: A
      total of 372 patients with FUO who hospitalized in Capital Medical University
      Affiliated Beijing Friendship Hospital were retrospectively analyzed from January
      2003 to August 2013. All the patients were divided into two groups: group A
      (January 2003 - December 2007) and group B (January 2008-August 2013). Diagnosis
      rate, duration of hospitalization (days) and time to diagnosis between the two
      groups were artificially compared. RESULTS: Of the 372 FUO cases, 336 were
      positively diagnosed with a diagnosis rate of 90.3%. Infectious diseases were
      still the primary causes of FUO (60.2%), including 72 cases (32.1%) of
      tuberculosis. Connective tissue diseases accounted for 12.9% of the FUO cases,
      malignancies were 8.3%, and miscellaneous diseases were 8.9%. Yet thirty six
      patients (9.7%) could not be confirmed until they were discharged from hospital.
      The duration of fever in patients with malignancies was longer than that with
      infectious diseases [60.0 (30.0, 90.0) days vs 30.0 (20.0, 60.0) days, P =
      0.003]. Time to diagnosis of connective tissue disease and malignancies was
      longer than infectious diseases [(12.0(7.3, 18.8) days and 11.0 (7.0, 18.0) vs
      5.0 (3.0, 8.0) days, both P values = 0.000]. The duration of hospitalization in
      group A was longer than that of group B [17.0(12.0, 30.0) days vs 14.0(10.0,
      20.0) days, P = 0.000]. The diagnosis rate and time to diagnosis of group A were
      similar with those of group B. The proportion of connective tissue diseases in
      group A was higher than group B (18.1% vs 9.2%,chi(2) = 6.201, P = 0.013) . The
      proportion of infectious disease, malignancies and miscellaneous diseases was not
      significantly different between the two groups. CONCLUSIONS: Infectious diseases
      are the major causes of FUO, and the most common cause is tuberculosis.
      Connective tissue diseases and malignancies are the second and third causes of
      FUO. The duration of fever and time to diagnosis are significantly different
      between the different origins.

PMID- 24857306
TI  - [The correlation of vitamin D level and vitamin D-binding protein gene
      polymorphism in chronic obstructive pulmonary disease].
AB  - OBJECTIVE: To assess the correlation of serum 25-hydroxyvitamin D (25-OHD) levels
      with vitamin D-binding protein (the group-specific component, GC) gene
      polymorphism in chronic obstructive pulmonary disease (COPD). METHODS: In a cross
      sectional case-control study, 250 participants, including 116 COPD patients with
      smoking history and 134 healthy smokers, were investigated. A questionnaire about
      smoking history, vitamin D intake and comorbidities was collected. General
      pulmonary function was done by routine. Serum 25-OHD levels were detected by
      ELISA. The genetic variants (rs4588 and rs7041) were genotyped by real time
      fluorescence polymerase chain reaction (RT-PCR) with TaqMan probe technology.
      RESULTS: The COPD patients had lower serum vitamin D level than the smoker
      subjects (36.58 nmol/L vs 43.80 nmol/L, P < 0.001). In the COPD patients, vitamin
      D level was 39.43 nmol/L in those with percentage of predicted forced expiratory
      volume in 1 second (FEV1%pred) greater than or equal to 80%.In other groups with
      FEV1%pred 50%-80%, 30%-50% and lower than 30%, vitamin D levels were 35.32
      nmol/L, 32.21 nmol/L, 26.25 nmol/L respectively (P < 0.01). Moreover, there was a
      significant relevance of 25-OHD levels with FEV1%pred in both COPD patients and
      healthy smokers (r(2) = 1.911; P < 0.000 1). The mean 25-OHD concentration had a
      negative correlation with Global Initiative for Obstructive Lung Disease (GOLD)
      stages. Homozygous carriers of vitamin D-binding protein gene rs7041 T allele
      were independently related to 25-OHD levels and susceptibility of COPD (P < 0.01;
      OR = 2.140, 95%CI 1.157-3.959, P = 0.015 respectively). CONCLUSIONS: Patients
      with COPD are at high risk of vitamin D deficiency and the severity of COPD is
      inversely correlated with vitamin D levels. Furthermore, homozygous carrier of
      rs7041 T allele influences 25-OHD serum levels and is related to susceptibility
      of COPD, which may be a potential candidate gene for screening COPD.

PMID- 24857307
TI  - Relationship between exchange block time in swim starts and final performance in
      relay races in international championships.
AB  - The purpose of this study was to investigate the association between relay
      exchange block time and final performance in 4 * 100-m and 4 * 200-m freestyle
      and 4 * 100-m medley relays as a function of sex (men and women) and
      classification (medallists and non-medallists) in international competitions.
      Nineteen international competitions covering a 13-year period (2000-2012) were
      analysed retrospectively. The data corresponded to a total of 827 team relay
      histories (407 men, 420 women). Kruskal-Wallis and Mann-Whitney tests were
      performed to determine any differences by sex, classification, and event.
      Similarly, the relationship between the exchange block times and final
      performance was examined by means of a Pearson correlation analysis. In the three
      events, the men's exchange block times were shorter than those of the women
      (eta(2) = 0.049-0.109; P < 0.001). The exchange block time was especially
      relevant for the women's relay medallists in the 4 * 100-m freestyle (r = 0.306,
      P = 0.021) and 4 * 100-m medley (r = 0.385, P = 0.011), while for men the
      relationship was clearer for the non-medallists. These results suggest that the
      exchange block time should be considered as one of the performance parameters of
      swimming relay starts, and thus should be included explicitly as part of
      training. In particular, the coach could design training targeted at
      standardising an optimal exchange block time equal to or less than that expected
      for other teams in the competition.

PMID- 24857308
TI  - MS2 bacteriophage reduction and microbial communities in biosand filters.
AB  - This study evaluated the role of physical and biological filter characteristics
      on the reduction of MS2 bacteriophage in biosand filters (BSFs). Three full-scale
      concrete Version 10 BSFs, each with a 55 cm sand media depth and a 12 L charge
      volume, reached 4 log10 reduction of MS2 within 43 days of operation. A
      consistently high reduction of MS2 between 4 log10 and 7 log10 was demonstrated
      for up to 294 days. Further examining one of the filters revealed that an average
      of 2.8 log10 reduction of MS2 was achieved within the first 5 cm of the filter,
      and cumulative virus reduction reached an average of 5.6 log10 after 240 days.
      Core sand samples from this filter were taken for protein, carbohydrate, and
      genomic extraction. Higher reduction of MS2 in the top 5 cm of the sand media
      (0.56 log10 reduction per cm vs 0.06 log10 reduction per cm for the rest of the
      filter depth) coincided with greater diversity of microbial communities and
      increased concentrations of carbohydrates. In the upper layers, "Candidatus
      Nitrosopumilus maritimus" and "Ca. Nitrospira defluvii" were found as dominant
      populations, while significant amounts of Thiobacillus-related OTUs were detected
      in the lower layers. Proteolytic bacterial populations such as the classes
      Sphingobacteria and Clostridia were observed over the entire filter depth. Thus,
      this study provides the first insight into microbial community structures that
      may play a role in MS2 reduction in BSF ecosystems. Overall, besides media
      ripening and physical reduction mechanisms such as filter depth and long
      residence time (45 min vs 24 +/- 8.5 h), the establishment of chemolithotrophs
      and proteolytic bacteria could greatly enhance the reduction of MS2. 

PMID- 24857309
TI  - Ultrasound-guided dilatation and curettage in life-threatening cesarean scar
      ectopic pregnancy.

PMID- 24857311
TI  - 'Mevrouw, there is more regret and failure following a sterilization together
      with a caesarean, and all those hormones in pregnancy preclude rational
      judgement'.

PMID- 24857310
TI  - Endometriosis and type 1 allergies/immediate type hypersensitivity: a systematic
      review.
AB  - Endometriosis is a chronic and debilitating disorder affecting up to 5-10% of
      women in reproductive age. Investigators have described deficiency in cellular
      immunity in women suffering from endometriosis, and in the recent years
      endometriosis has been linked to other diseases, allergic disease being one of
      them. The objective of this paper is to systematically review the existing
      literature on the possible association between endometriosis and allergic
      disease. This review is based on the recommendations by the preferred reporting
      of systematic reviews and meta-analysis (PRISMA) statement. PubMed and Embase
      were searched for studies on women diagnosed with endometriosis and with
      manifestations of allergic disease who were compared to a reference group. Out of
      316 articles screened, 6 were reviewed and 5 ultimately met the inclusion
      criteria. Four out of the five studies reported a positive correlation between
      endometriosis and allergic manifestations, including hay fever, sinus allergic
      rhinitis, and food intolerance/sensitivities (food allergy). Investigators
      reported an odds ratio (OR) as high as 4.28 (95% CI: 2.93-6.27) for a positive
      history of allergy among women suffering from endometriosis. Equivocal results
      were found on asthma prevalence in women with endometriosis. Due to the
      heterogeneity of the included studies, no meta-analyses could be performed. The
      available literature clearly indicates that women with endometriosis are at an
      increased risk of allergic disorders compared to controls, but due to the lack of
      a concise definition of allergic disease and therefore diagnostic criteria,
      further studies are needed in order to draw firm conclusions on the association
      between endometriosis and allergic disease. 

PMID- 24857312
TI  - Laparoscopic management of an interstitial pregnancy in a sub-fertility patient:
      a case report depicting the challenges to diagnose and manage this rare
      condition.

PMID- 24857313
TI  - Epigenetics, a key for unlocking complex CNS disorders? Therapeutic implications.
AB  - Aberrant changes in gene function are believed to be involved in a wide spectrum
      of human disease including behavioral, cognitive and neurodegenerative
      pathologies. Most of the attention in last few decades have focused on changes in
      gene sequence as a cause of gene dysfunction leading to disease and mental health
      disorders. Germ line mutations or other alterations in the sequence of DNA that
      associate with different behavioral and neurological pathologies have been
      identified. However, sequence alterations explain only a small fraction of the
      cases. In addition there is evidence for "gene-environment" interactions in the
      brain suggesting mechanisms that alter gene function and the phenotype through
      environmental exposure. Genes are programmed by "epigenetic" mechanisms such as
      chromatin structure, chromatin modification and DNA methylation. These mechanisms
      confer on similar sequences different identities during cellular differentiation.
      Epigenetic differences are proposed to be involved in differentiating gene
      function in response to different environmental contexts and could result in
      alterations in functional gene networks that lead to brain disease. Epigenetic
      markers could serve important biomarkers in brain and behavioral diseases.
      Moreover, epigenetic processes are potentially reversible pointing to epigenetic
      therapeutics in psychotherapy. 

PMID- 24857314
TI  - Inflammation targeted Gd(3+)-based MRI contrast agents imaging tumor and
      rheumatoid arthritis models.
AB  - Inflammatory responses are closely related to cancer progression and several
      diseases. Anti-inflammatory drugs that bind to inducible enzymes can be used as
      biomarkers for molecular imaging. Selective targeted contrast agents are expected
      to improve contrast-to-noise ratio (CNR) in MRI at the site of inflammation. In
      this work, three new Gd(3+) DO3A-amide MRI contrast agents (CAs) that conjugated
      to mefenamic acid (MA), a commonly used nonsteroidal anti-inflammatory drug
      (NSAID), through different linkers, ethylenediamine (GdL1), 2,2'-oxidiethylamine
      (GdL2) and 4,7,10-trioxa-1,13-tridecanediamine (GdL3) were studied. Their
      relaxivities were GdL1 (4.74 mM(-1) s(-1)), GdL2 (4.77 mM(-1) s(-1)), and GdL3
      (4.95 mM(-1) s(-1)) at 400 MHz at 25  degrees C. Their serum albumin binding
      properties were studied by tryptophan emission-quenching experiments, with GdL1
      showing a preferential binding toward HSA and BSA as compared with GdL2 and GdL3.
      They showed low cytotoxicities toward HeLa cells at high concentration (0.5 mM)
      and high cellular uptake in U87 cells as compared with GdDOTA. In vivo MRI showed
      increased T1-weighted contrast after intravenous injection of the agents.
      Moreover, T1 contrast was significantly enhanced for 1.5 h in the U87 tumor model
      and 2 h in the arthritis joint in adjuvant-induced arthritis (AIA) model at
      dosages of 0.1 and 0.03 mmol/kg, respectively. Most of the agents were cleared at
      24 h post-administration in the AIA model with no observable T1 contrast. GdL1-3
      showed superior retentions and intensity enhancements (IEs) at the kidney, liver,
      tumor, and arthritis joint to those of GdDOTA. GdL3 showed the highest relaxivity
      and IE at the arthritis joint and is therefore a potential candidate to be
      developed as MRI CAs that target inflammation. 

PMID- 24857316
TI  - Origin of the pinking phenomenon of white wines.
AB  - Pinking is the terminology used for the salmon-red blush color that may appear in
      white wines produced exclusively from white grape varieties. The isolation of
      pinking compounds and their analysis by RP-HPLC-DAD and ESI-MS(n) showed that the
      origin of the pinking phenomenon in white wines from Vitis vinifera L. of Siria
      grape variety are the anthocyanins, mainly malvidin-3-O-glucoside. The analysis
      showed that the anthocyanins were located both in the pulp and in the skin. Wine
      pinking severity was negatively related with the increase of the average
      temperature of the first 10 days of October, the final period of grape
      maturation. The minimum amount of anthocyanins needed for the pink color
      visualization in wine was 0.3 mg/L. The appearance of pinking in white wines
      after bottling is due to the lowering of free sulfur dioxide, which leads to an
      increase of the relative amount of the anthocyanins red flavylium form and their
      polymerization, resulting in the formation of colored compounds resistant to pH
      changes and sulfur dioxide bleaching. 

PMID- 24857320
TI  - Association between metabolic syndrome and periodontal disease measures in
      postmenopausal women: the Buffalo OsteoPerio study.
AB  - BACKGROUND: The objective of this study is to characterize the association
      between metabolic syndrome (MetS) and periodontitis in women, for which there is
      limited evidence. METHODS: Cross-sectional associations between MetS and
      periodontitis were examined in 657 postmenopausal women aged 50 to 79 years
      enrolled in a periodontal disease study ancillary to the Women's Health
      Initiative Observational Study. Whole-mouth measures of alveolar crest height
      (ACH), clinical attachment level (CAL), probing depth (PD), gingival bleeding,
      and supragingival plaque and measures to define MetS using National Cholesterol
      Education Program criteria were from a clinical examination. Study outcomes were
      defined as: 1) mean ACH >=3 mm, two sites >=5 mm, or tooth loss to periodontitis;
      2) >=2 sites with CAL >=6 mm and >=1 site with PD >=5 mm; 3) gingival bleeding at
      >=50% of sites; and 4) supragingival plaque at >=50% of sites. Logistic
      regression was used to estimate odds ratios (ORs) and 95% confidence intervals
      (CIs). RESULTS: In unadjusted analyses, MetS (prevalence: 25.6%) was
      significantly associated with supragingival plaque (OR = 1.74; 95% CI: 1.22 to
      2.50) and non-significantly associated with periodontitis defined by ACH (OR =
      1.23; 95% CI: 0.81 to 1.85) and gingival bleeding (OR = 1.20; 95% CI: 0.81 to
      1.77). Adjustment for age, smoking, and other confounders attenuated observed
      associations, though supragingival plaque remained significant (OR = 1.47; 95%
      CI: 1.00 to 2.16; P = 0.049). MetS was not associated with periodontitis defined
      by CAL and PD. CONCLUSIONS: A consistent association between MetS and measures of
      periodontitis was not seen in this cohort of postmenopausal women. An association
      between MetS and supragingival plaque requires further investigation.

PMID- 24857321
TI  - Periodontal and serum protein profiles in patients with rheumatoid arthritis
      treated with tumor necrosis factor inhibitor adalimumab.
AB  - BACKGROUND: Tumor necrosis factor (TNF)-alpha inhibitor has been shown to affect
      the periodontal condition of patients with rheumatoid arthritis (RA). The aim of
      the present study is to assess the effect of a fully humanized anti-TNF-alpha
      monoclonal antibody, adalimumab (ADA), on the periodontal condition of patients
      with RA and to compare serum protein profiles before and after ADA therapy.
      METHODS: The study participants consisted of 20 patients with RA treated with
      ADA. Clinical periodontal and rheumatologic parameters and serum cytokine levels
      were evaluated at baseline and 3 months later. Serum protein spot volume was
      examined with two-dimensional sodium dodecyl sulfate polyacrylamide gel
      electrophoresis. Proteins with significant difference in abundance before and
      after ADA therapy were found and identified using mass spectrometry and protein
      databases. RESULTS: The patients showed a significant decrease in gingival index
      (P = 0.002), bleeding on probing (P = 0.003), probing depth (P = 0.002), disease
      activity score including 28 joints using C-reactive protein (P <0.001), and serum
      levels of TNF-alpha (P <0.001) and interleukin-6 (P <0.001) after ADA medication,
      although plaque levels were comparable. Among a total of 495 protein spots
      obtained, nine spots were significantly decreased in abundance at reassessment,
      corresponding to complement factor H, phospholipase D, serum amyloid A,
      complement component 4, and alpha-1-acid glycoprotein (P <0.01). CONCLUSION:
      These results suggest a beneficial effect of ADA therapy on the periodontal
      condition of patients with RA, which might be related to differences in serum
      protein profiles before and after ADA therapy.

PMID- 24857322
TI  - Evaluation of periodontitis and bone loss in patients undergoing hemodialysis.
AB  - BACKGROUND: Chronic kidney disease has been a worldwide public health challenge
      and also a risk factor for oral health. The objectives of this study are to
      investigate the periodontal status in Chinese patients undergoing hemodialysis
      (HD) and assess periodontal bone loss (BL) using cone-beam computerized
      tomography (CBCT). METHODS: The patients in the HD and control groups received
      periodontal and CBCT examinations in the same period. Age, sex, and HD details
      were obtained from a hospital database. Periodontal status was evaluated using
      the community periodontal index (CPI) and clinical attachment loss (AL).
      Periodontal BL was measured by the distance from the cemento-enamel junction to
      the alveolar crest using CBCT. The distance between the furcation upper and lower
      boundaries was considered the furcation defect. RESULTS: One hundred two patients
      undergoing HD and 204 control patients were enrolled. As for the demographic data
      and number of remaining teeth for each patient, there was no significant
      difference between HD and control groups. The CPI and AL showed statistical
      differences (P <0.001). The results of periodontal BL indicated that the patients
      undergoing HD had significantly more BL at their mandibular first premolars and
      first molars than did patients in the control group (P <0.01) at every site
      except the disto-buccal one (P <0.05). As for the furcation defects, the distance
      for the patients undergoing HD was nearly double that of the patients in the
      control group (P <0.001). CONCLUSION: Compared with the generally healthy
      population, periodontitis and periodontal BL were significantly more severe in
      the Chinese patients undergoing HD.

PMID- 24857323
TI  - Effect of enamel matrix derivative on periodontal wound healing and regeneration
      in an osteoporotic model.
AB  - BACKGROUND: Despite the worldwide increased prevalence of osteoporosis, no data
      are available evaluating the effect of an enamel matrix derivative (EMD) on the
      healing of periodontal defects in patients with osteoporosis. This study aims to
      evaluate whether the regenerative potential of EMD may be suitable for
      osteoporosis-related periodontal defects. METHODS: Forty female Wistar rats (mean
      body weight: 200 g) were used for this study. An osteoporosis animal model was
      carried out by bilateral ovariectomy (OVX) in 20 animals. Ten weeks after OVX,
      bilateral fenestration defects were created at the buccal aspect of the first
      mandibular molar. Animals were randomly assigned to four groups of 10 animals per
      group: 1) control animals with unfilled periodontal defects; 2) control animals
      with EMD-treated defects; 3) OVX animals with unfilled defects; and 4) OVX
      animals with EMD-treated defects. The animals were euthanized 28 days later, and
      the percentage of defect fill and thickness of newly formed bone and cementum
      were assessed by histomorphometry and microcomputed tomography (micro-CT)
      analysis. The number of osteoclasts was determined by tartrate-resistant acid
      phosphatase (TRAP), and angiogenesis was assessed by analyzing formation of blood
      vessels. RESULTS: OVX animals demonstrated significantly reduced bone volume in
      unfilled defects compared with control defects (18.9% for OVX animals versus
      27.2% for control animals) as assessed by micro-CT. The addition of EMD in both
      OVX and control animals resulted in significantly higher bone density (52.4% and
      69.2%, respectively) and bone width (134 versus 165MUm) compared with untreated
      defects; however, the healing in OVX animals treated with EMD was significantly
      lower than that in control animals treated with EMD. Animals treated with EMD
      also demonstrated significantly higher cementum formation in both control and OVX
      animals. The number of TRAP-positive osteoclasts did not vary between untreated
      and EMD-treated animals; however, a significant increase was observed in all OVX
      animals. The number of blood vessels and percentage of new vessel formation was
      significantly higher in EMD-treated samples. CONCLUSIONS: The results from the
      present study suggest that: 1) an osteoporotic phenotype may decrease periodontal
      regeneration; and 2) EMD may support greater periodontal regeneration in patients
      suffering from the disease. Additional clinical studies are necessary to fully
      elucidate the possible beneficial effect of EMD for periodontal regeneration in
      patients suffering from osteoporosis.

PMID- 24857324
TI  - Kounis syndrome caused by aspirin-induced asthma.

PMID- 24857325
TI  - Chronic inflammation reduces cardiac relative telomere length without altering
      left ventricular chamber function.

PMID- 24857327
TI  - The danger of wearing your heart on your sleeve.

PMID- 24857326
TI  - Dose matters! Optimisation of guideline adherence is associated with lower
      mortality in stable patients with chronic heart failure.
AB  - AIMS: Guidelines have been published for improving management of chronic heart
      failure (CHF). We examined the association between improved guideline adherence
      and risk for all-cause death in patients with stable systolic HF. METHODS: Data
      on ambulatory patients (2006-2010) with CHF and reduced ejection fraction (HF
      REF) from the Austrian Heart Failure Registry (HIR Austria) were analysed. One
      year clinical data and long-term follow-up data until all-cause death or data
      censoring were available for 1014 patients (age 65 [55-73], male 75%, NYHA class
      I 14%, NYHA II 56%, NYHA III/IV 30%). A guideline adherence indicator (GAI [0
      100%]) was calculated for each patient at baseline and after 12 +/- 3 months that
      considered indications and contraindications for ACE-I/ARB, beta blockers, and
      MRA. Patients were considered DeltaGAI-positive if GAI improved to or remained at
      high levels (>= 80%). DeltaGAI50+ positivity was ascribed to patients achieving a
      dose of >= 50% of suggested target dose. RESULTS: Improvements in GAI and GAI50+
      were associated with significant improvements in NYHA class and NT-proBNP (1728
      [740-3636] to 970 [405-2348]) (p<0.001). Improvements in GAI50+, but not GAI,
      were independently predictive of lower mortality risk (HR 0.55 [95% CI 0.34-0.87;
      p=0.01]) after adjustment for a large variety of baseline parameters and
      hospitalisation for heart failure during follow-up. CONCLUSIONS: Improvement in
      guideline adherence with particular emphasis on dose escalation is associated
      with a decrease in long-term mortality in ambulatory HF-REF subjects surviving
      one year after registration.

PMID- 24857328
TI  - Buruli ulcer disease in Republic of the Congo.

PMID- 24857330
TI  - Web-based objective structured clinical examination with remote standardized
      patients and Skype: resident experience.
AB  - OBJECTIVE: Using Skype and remote standardized patients (RSPs), investigators
      sought to evaluate user acceptance of a web-based objective structured clinical
      examination (OSCE) among resident physicians. METHODS: After participating in
      four web-based clinical encounters addressing pain with RSPs, 59 residents from
      different training programs, disciplines and geographic locations completed a 52
      item questionnaire regarding their experience with Skype and RSPs. Open-ended
      responses were solicited as well. RESULTS: The majority of participants (97%)
      agreed or strongly agreed the web-based format was convenient and a practical
      learning exercise, and 90% agreed or strongly agreed the format was effective in
      teaching communication skills. Although 93% agreed or strongly agreed they could
      communicate easily with RSPs using Skype, 80% preferred traditional face-to-face
      clinical encounters, and 58% reported technical difficulties during the
      encounters. Open-ended written responses supported survey results. CONCLUSION:
      Findings from this study expose challenges with technology and human factors, but
      positive experiences support the continued investigation of web-based OSCEs as a
      synchronous e-learning initiative for teaching and assessing doctor-patient
      communication. Such educational programs are valuable but unlikely to replace
      face-to-face encounters with patients. PRACTICE IMPLICATIONS: This web-based OSCE
      program provides physician learners with additional opportunity to improve doctor
      patient communication.

PMID- 24857331
TI  - Greater professional empathy leads to higher agreement about decisions made in
      the consultation.
AB  - OBJECTIVE: To examine the relationship between professional expression of empathy
      and agreement about decisions made in the consultation. METHODS: Consultations
      between 86 individuals with diabetes and four dieticians were audio-recorded.
      Immediately following consultations patients and dieticians independently
      reported decisions made in a booklet. Audio-recordings were coded directly for
      empathy using an amended version of the empathic communication coding system
      (ECCS). RESULTS: Empathy correlated significantly with patient and professional
      agreement about decisions made in the consultation (tau=.283, p=.0005). Multiple
      regression analysis indicates that for each dietician the greater the empathy the
      higher the level of agreement about decisions (p<.0005). Professional empathic
      response to patients statements of challenge was a significant factor in
      increasing agreement about decisions (p=.008). CONCLUSION: Results support the
      hypothesis that greater professional empathy will result in greater agreement
      about decisions made in consultations. PRACTICE IMPLICATIONS: Findings have
      implications for empathy training and provide guidance on the communication
      skills needed to support expression of empathy. Patient and professional
      agreement about decisions made provides a simple marker of effectiveness and
      highlights the importance of empathy as a seminal component of professional
      communication skills during a patient consultation.

PMID- 24857332
TI  - The importance of the general practitioner as an information source for patients
      with hereditary haemochromatosis.
AB  - OBJECTIVE: To explore hereditary haemochromatosis (HH) patients' perspectives on
      genetic information, namely the types of sources used, preferred or trusted.
      METHODS: A survey online was conducted by the European Federation of Associations
      of Patients with Haemochromatosis (EFAPH) and applied to members of nine National
      Associations. RESULTS: From a total of 1019 validated questionnaires, 895
      respondents had performed a genetic testing for HH. From these, 627 self-declared
      that they were sufficiently informed about the implications of the genetic test
      to their health. The majority (66%) obtained the information from a specialist
      doctor, but would like to obtain it from the family doctor. However, the
      specialist was still the one they trusted more (69%). Regarding the 298
      respondents who did not feel sufficiently informed, the majority (78%) also would
      like to have information from the family doctor although they also trusted the
      specialist more (75%). A different perspective was reported when patients were
      asked about the implications of the genetic testing to their family members,
      where the majority of respondents preferred obtaining information from a
      specialist (69%). CONCLUSION: This study elucidates the patients' needs for
      information and identifies the general practitioner (GP) as the preferred source
      to obtain information about HH. PRACTICE IMPLICATIONS: These results may have
      important implications in future strategies for HH awareness, giving a special
      emphasis on GPs as the main players.

PMID- 24857333
TI  - RBE of ion beams in hypofractionated radiotherapy (SBRT).
AB  - An important advantage for the application of carbon ion beams in tumour therapy
      is their increased relative biological effectiveness (RBE) as compared to
      conventional photon radiation. Since RBE among other factors depends on the dose
      level, the precise knowledge of the RBE dependence on the dose is of particular
      importance for the comparison of different fractionation schemes, involving
      different doses per fraction. Here we describe some general properties of the RBE
      vs. dose dependence, which are determined using a simple modelling approach based
      on the linear-quadratic model as well as a more sophisticated predictive model
      for the description of RBE. We show that for both approaches the systematic
      dependence of RBE on the cell or tissue type as characterized by the alpha/beta
      ratio of the photon linear quadratic parameters is expected to be inverted at
      high doses as compared to low doses. We demonstrate that this inversion is not a
      model specific feature, but a rather generic feature resulting from the linear
      quadratic shape of dose response curves and the correlation between RBE and the
      photon alpha/beta-ratio. The results are discussed with respect to other
      modelling approaches and to their implications for clinical applications of
      carbon ion beams using hypofractionated treatment schedules. 

PMID- 24857334
TI  - Plain radiographs fail to reflect femoral offset in total hip arthroplasty.
AB  - Successful biomechanical reconstruction is a major goal in total hip arthroplasty
      (THA). We measured leg length (LL), global (GO) and femoral offset (FO) change on
      anteroposterior pelvis radiographs and on three-dimensional computed-tomography
      (3D-CT) with fiducial landmarks after cementless THA on 18 hips of cadaveric
      specimens. Measurements on radiographs were performed twice by four examiners and
      showed high interobserver (mean CCC >=0.79) and intraobserver agreements (mean
      ICC >=0.88). Mean differences between radiographic and 3D-CT measurements were
      1.0 (SD 2.0) mm for LL, 0.6 (SD 3.6) mm for GO and 1.4 (SD 5.2) mm for FO. 1% of
      radiographic LL-, 15% of GO- and 35% of FO measurements were outside a tolerance
      limit of 5mm. Radiographs seem acceptable for measuring LL/GO change but fail to
      reflect FO change in THA. 

PMID- 24857335
TI  - Mortality following hip arthroplasty--inappropriate use of National Joint
      Registry (NJR) data.
AB  - Mortality following hip arthroplasty is affected by a large number of confounding
      variables each of which must be considered to enable valid interpretation.
      Relevant variables available from the 2011 NJR data set were included in the Cox
      model. Mortality rates in hip arthroplasty patients were lower than in the age
      matched population across all hip types. Age at surgery, ASA grade, diagnosis,
      gender, provider type, hip type and lead surgeon grade all had a significant
      effect on mortality. Schemper's statistic showed that only 18.98% of the
      variation in mortality was explained by the variables available in the NJR data
      set. It is inappropriate to use NJR data to study an outcome affected by a
      multitude of confounding variables when these cannot be adequately accounted for
      in the available data set. 

PMID- 24857336
TI  - Reliability of PAX8 in clinical practice to accurately determine primary site of
      origin in female pelvic or abdominal lesions.
AB  - Female patients with gynecological malignancies can harbor peritoneal pelvic or
      abdominal lesions; however, other primary tumors can involve the peritoneum as
      well. Since sampling of the peritoneum now can be easily performed by fine needle
      aspiration or percutaneous biopsy, we have noticed an increase in such procedures
      as initial attempts to establish a diagnosis. PAX8 has been used alone or in
      combination with other tumor markers to accurately classify these lesions and
      determine primary site of origin; however, prior published studies determined
      expression of PAX8 within historically diagnosed cases. We reviewed the
      reliability of PAX8 to determine tumor type or primary site in 135 current
      clinical pelvic or abdominal lesions and highlight several pitfalls in its
      routine use, in particular, relying on the presumed expression pattern (positive
      or negative) within a given primary tumor and that poorly differentiated
      endometrial endometrioid carcinomas or undifferentiated carcinomas may have
      patchy PAX8 expression or even lose expression within the primary tumor or the
      metastasis. 

PMID- 24857337
TI  - Concurrent directional adaptation of reactive saccades and hand movements to
      target displacements of different size.
AB  - When eye and hand movements are concurrently aimed at double-step targets that
      call for equal and opposite changes of response direction (-10 degrees  for the
      eyes, +10 degrees  for the hand), adaptive recalibration of both motor systems is
      strongly attenuated; instead, hand but not eye movements are changed by
      corrective strategies (V. Grigorova et al., 2013a). The authors introduce a
      complementary paradigm, where double-step targets call for a -10 degrees  change
      of eye and a -30 degrees  change for hand movements. If compared to control
      subjects adapting only the eyes or only the hand, adaptive improvements were
      comparable for the eyes but were twice as large for the hand; in contrast, eye
      and hand aftereffects were comparable to those in control subjects. The authors
      concluded that concurrent exposure of eyes and hand to steps of the same
      direction but different size facilitated hand strategies, but didn't affect
      recalibration. This finding together with previous one (V. Grigorova et al.,
      2013a), suggests that concurrent adaptation of eyes and hand reveals different
      mechanisms of recalibration for step sign and step size, which are shared by
      reactive saccades and hand movements. However, hand mostly benefits from
      strategies provoked by the difference in target step sign and size.

PMID- 24857339
TI  - The management of breast cancer.
AB  - Because of its prevalence, breast cancer is a major public health problem
      although its prognosis has improved as a result of early screening and
      improvement in treatments. We now no longer refer to breast cancer in the
      singular, but to breast cancers, which have different prognoses and treatments
      depending on their molecular profile. 

PMID- 24857338
TI  - Pleomorphic hyalinizing angiectatic tumor of soft parts: case report with unusual
      ganglion-like cells and review of the literature.
AB  - Pleomorphic hyalinizing angiectatic tumor (PHAT) is a recently described, non
      metastasizing tumor of uncertain lineage. This tumor distributes equally between
      the genders and has a predilection for the subcutaneous soft tissue, particularly
      in lower extremity, other locations are rare. Based on the recent literature,
      PHAT is suspected to encompass the morphological spectrum with other tumors such
      as myxoinflammatory fibroblastic sarcoma (MIFS) and hemosiderotic fibrolipomatous
      tumor (HFLT), although cytogenetic data remain inconsistent. We report a case of
      PHAT that arose in the upper arm with unusual morphology which showed ganglion
      like cells similar to Reed-Sternberg-like cells found in MIFS. The tumor had
      strong immunohistochemical expression of CD34, CD99, and was negative for S-100.
      The ganglion-like cells were positive for both CD34 and CD68 but negative for
      CD30. The translocation between chromosome 1 and 10, a frequent finding of MIFS
      and HFLT, was not identified by FISH excluding the possibility of hybrid PHAT and
      MIFS. We conclude FISH can be a potential useful tool to separate PHAT with
      atypical morphology from hybrid tumor in doubted cases. Due to the rarity of PHAT
      and lack of consistent pathogenetic signatures, more cases and further studies
      will be needed to elucidate the pathogenesis and nature of this tumor. 

PMID- 24857340
TI  - Sex and gender influences on pharmacological response: an overview.
AB  - Research on the specific effects of sex and gender on pharmacokinetics and
      pharmacodynamics, as well as safety profile tolerability and drug efficacy, of
      medications remain meager because female animals and women have only recently
      been included in the pharmacological domain. To date, the influence of sex and
      gender on access to care and emotional factors, including patients and care
      provider dyads, the placebo effect, adherence, and safety profiles, are
      discussed. Furthermore, differences in drug responses, mainly for antidiabetic
      drugs, have been described. However, further studies are needed to explore the
      impact of sex and gender on reaching the most appropriate and tailored
      prescription for each patient, regardless of sex and gender.

PMID- 24857341
TI  - Endoscopic endonasal surgery for pituitary tumors. Results in a series of 121
      patients operated at the same center and by the same neurosurgeon.
AB  - INTRODUCTION: Pituitary adenomas account for approximately 15% of intracranial
      benign tumors. The neurosurgical results achieved since the endoscopic endonasal
      transsphenoidal (EET) approach was introduced in our center in 2005 are reported
      here. PATIENTS AND METHODS: A retrospective analysis of 121 patients with sellar
      lesions (58% females, age 55.7 +/- 16 years, range 18-82) who underwent EET
      surgery from February 2005 to January 2012 and were followed up for a mean time
      of 4.58 years (range 1.08-8.58). RESULTS: Six Rathke cleft cysts (3 intra
      suprasellar, 1 intrasellar, 2 suprasellar); 114 pituitary adenomas (16
      microadenomas, 98 macroadenomas), and 1 case of normal MRI were included.
      Baseline findings included hormonal changes in 59 patients (48,7%) and visual
      field changes in 38 patients (31%); in 7 patients (5.8%), clinical presentation
      was pituitary apoplexy. Complete resection was achieved in 77 patients (63.6%),
      subtotal resection in 29 (23.9%), and partial resection in 15 (12.3%). In
      patients with Grade 3 and 4 cavernous sinus invasion, resection was subtotal in
      30% (12/39) and complete in 46% (18/39). Hormonal remission was achieved in 16
      patients with Cushing disease (84%), 18 patients with prolactinoma (78.2%), and
      18 patients with acromegaly (85,7%). There were 12 cases (9%) of cerebrospinal
      fluid leak, 4 cases of diabetes insipidus, and 3 cases with transient
      SIADH/hyponatremia. Seven patients developed panhypopituitarism. Postoperative
      mortality rate was 2.4%. One hundred and three patients (85.3%) were discharged
      from the hospital less than 48 hours after surgery. CONCLUSION: Our results are
      similar to those reported by renowned pituitary units. Results achieved using an
      endoscopic approach in pituitary neurosurgery are better than those of
      microneurosurgery for cavernous sinus invasion.

PMID- 24857342
TI  - Single molecule FRET analysis of the 11 discrete steps of a DNA actuator.
AB  - DNA hybridization allows the design and assembly of dynamic DNA-based molecular
      devices. Such structures usually accomplish their function by the addition of
      fuel strands that drive the structure from one conformation to a new one or by
      internal changes in DNA hybridization. We report here on the performance and
      robustness of one of these devices by the detailed study of a dynamic DNA
      actuator. The DNA actuator was chosen as a model system, as it is the device with
      most discrete states to date. It is able to reversibly slide between 11 different
      states and can in principle function both autonomously and nonautonomously. The
      11 states of the actuator were investigated by single molecule Forster Resonance
      Energy Transfer (smFRET) microscopy to obtain information on the static and
      dynamic heterogeneities of the device. Our results show that the DNA actuator can
      be effectively locked in several conformations with the help of well-designed DNA
      lock strands. However, the device also shows pronounced static and dynamic
      heterogeneities both in the unlocked and locked modes, and we suggest possible
      structural models. Our study allows for the direct visualization of the
      conformational diversity and movement of the dynamic DNA-based device and shows
      that complex DNA-based devices are inherently heterogeneous. Our results also
      demonstrate that single molecule techniques are a powerful tool for structural
      dynamics studies and provide a stringent test for the performance of molecular
      devices made out of DNA. 

PMID- 24857343
TI  - Interactions of a water-soluble fullerene derivative with amyloid-beta
      protofibrils: dynamics, binding mechanism, and the resulting salt-bridge
      disruption.
AB  - Alzheimer's disease (AD) is associated with the pathological self-assembly of
      amyloid-beta (Abeta) peptides into beta-sheet-rich oligomers and insoluble
      amyloid fibrils. Experimental studies reported that 1,2
      (dimethoxymethano)fullerene (DMF), a water-soluble fullerene derivative, inhibits
      strongly Abeta peptide aggregation at the early stage. However, the interaction
      and binding mechanisms are not well understood. In this study, we have
      investigated the detailed interaction of a DMF molecule with a fibrillar hexamer
      of full-length Abeta42 and the resulting structural alterations by performing
      multiple all-atom explicit solvent molecular dynamics (MD) simulations. Starting
      from different initial states with a minimum distance of 2 nm between the DMF and
      the Abeta protofibril, our MD simulations show that the DMF binds to the Abeta
      protofibril via both slow and fast binding processes. Three dominant binding
      sites are identified: the central hydrophobic core (CHC) site (17LVFFA21), the
      turn site (27NKGAI31), and the C-terminal beta-sheet site consisting of the
      smallest side-chain residue glycine and hydrophobic residues (31IIGLMVGGVVI41).
      Binding energy analyses reveal the importance of pi-stacking interactions,
      especially in the CHC site, hydrophobic interactions, and curvature matching.
      Strikingly, we find that the binding of DMF to the turn region can disrupt the
      D23-K28 salt-bridge that is important for the Abeta fibrillation. These results
      provide molecular insight into the binding mechanism of fullerene to Abeta
      protofibrils and offer new routes for the therapeutic drug design using fullerene
      derivatives against AD. 

PMID- 24857344
TI  - Role of expert centres in the management of sarcomas--a UK perspective.
AB  - Sarcomas are a rare group of tumours with many differing behaviours and
      histologies. The generally poor outcomes for patients with sarcoma have not
      significantly improved over recent years in the United Kingdom. The reasons for
      this are multi-factorial but delayed diagnosis plays an important role.
      Developing patient pathways and clinical guidelines is critical to improving
      patient outcomes as well as raising awareness of sarcoma in primary and secondary
      care. Expert centres play a key role in diagnosis and the complex multimodality
      treatment of sarcoma; furthermore centralising of care is critical to improving
      outcomes as this where multidisciplinary expertise is concentrated. In this
      review we explore the current role of the expert centre from a United Kingdom
      (UK) perspective and compare and contrast this with practice elsewhere. 

PMID- 24857345
TI  - A phase II study of erlotinib in gemcitabine refractory advanced pancreatic
      cancer.
AB  - BACKGROUND: Erlotinib induced skin toxicity has been associated with clinical
      benefit in several tumour types. This phase II study evaluated the efficacy of
      erlotinib, dose escalated to rash, in patients with advanced pancreatic cancer
      previously treated with gemcitabine. METHODS: Erlotinib was given at an initial
      dose of 150 mg/day, and the dose was escalated by 50mg every 2 weeks (to a
      maximum of 300 mg/day) until >grade 1 rash or other dose limiting toxicities
      occurred. Erlotinib pharmacokinetics were performed, and baseline tumour tissue
      was collected for mutational analysis and epidermal growth factor receptor (EGFR)
      expression. The primary end-point was the disease control rate (objective
      response and stable disease >8 weeks). RESULTS: Fifty-one patients were accrued,
      and 49 received treatment. Dose-escalation to 200-300 mg of erlotinib was
      possible in 9/49 (18%) patients. The most common ? grade 3 adverse events
      included fatigue (6%), rash (4%) and diarrhoea (4%). Thirty-seven patients were
      evaluable for response, and the best response was stable disease in 12 patients
      (32% (95% confidence interval (CI) 17-47%)). Disease control was observed in nine
      patients (24% (95% CI: 10-38%)). Median survival was 3.8 months, and 6 month
      overall survival rate was 32% (95% CI 19-47%). Mutational analysis and EGFR
      expression were performed on 29 patients, with 93% having KRAS mutations, none
      having EGFR mutations, and 86% expressing EGFR. Neither KRAS mutational status
      nor EGFR expression was associated with survival. CONCLUSIONS: Erlotinib dose
      escalated to rash was well tolerated but not associated with significant efficacy
      in non-selected patients with advanced pancreatic cancer.

PMID- 24857346
TI  - Infection with Mansonella perstans Nematodes in Buruli Ulcer Patients, Ghana.
AB  - During August 2010-December 2012, we conducted a study of patients in Ghana who
      had Buruli ulcer, caused by Mycobacterium ulcerans, and found that 23% were co
      infected with Mansonella perstans nematodes; 13% of controls also had M. perstans
      infection. M. perstans co-infection should be considered in the diagnosis and
      treatment of Buruli ulcer. 

PMID- 24857349
TI  - Non-ophthalmological presentation of imported loiasis.

PMID- 24857350
TI  - Hemichorea in a patient with diabetic ketoacidosis.
AB  - BACKGROUND: Chorea is a common presenting feature of metabolic disorders,
      including nonketotic hyperglycemia in patients with type 2 diabetes mellitus, but
      rarely has been reported in diabetic ketoacidosis, hypothyroidism and vitamin B12
      deficiency. METHODS: Review the literature for reported cases of chorea as a
      presenting manifestation in metabolic disorders. RESULTS: We report a case of
      hemichorea in a patient with type 2 diabetes mellitus complicated by diabetic
      ketoacidosis. The patient had a two day history of right sided hemichorea and
      decreased level of consciousness. Initial laboratory studies revealed
      hyperglycemia, ketosis and an anion gap metabolic acidosis consistent with
      diabetic ketoacidosis. Once treatment was started the choreiform movements
      significantly improved over three weeks. CONCLUSION: Although DKA has been rarely
      reported as a trigger for chorea, it should be in the differential diagnosis of a
      patient presenting with an acute chorea. Given the reversible nature of this
      disease, early recognition and treatment are imperative.

PMID- 24857351
TI  - New IDH1 I113T mutation associated with BRAF V600E mutation: new driver of
      gliomagenesis?
AB  - BACKGROUND: IDH mutations and BRAF mutations are classically mutually exclusive
      and usually associated with infiltrative or circumscribed gliomas and
      glioneuronal tumors respectively. CASE REPORT: We report the case of a 26-year
      old man with intracranial hypertension revealing voluminous right frontal lesion.
      Surgical resection was performed and pathological examination found two distinct
      tumoral areas: a glioma-like area with calcification without mitosis; a second
      with pleomorphic glial cells with higher Mib index, high CD34 expression and
      endothelial proliferation. No necrosis was recorded. Molecular analyses revealed
      both IDH1 I113T and BRAF V600E mutations. Although this glioma was difficult to
      clarify, diagnosis of pleomorphic xanthoastrocytoma with anaplastic feature was
      suggested based on the association of some pathological feature (eosinophilic
      granular bodies, reticulin network and diffuse CD34 expression) and the BRAF
      V600E mutation. CONCLUSION: We report a new IDH1 mutation associated with BRAF
      mutation in a very unusual glial tumor.

PMID- 24857352
TI  - Neuroprotective effect of cathodal transcranial direct current stimulation in a
      rat stroke model.
AB  - Experimental focal brain ischemia generates in the penumbra recurrent
      depolarizations which spread across the injured cortex inducing infarct growth.
      Transcranial direct current stimulation can induce a lasting, polarity-specific,
      modulation of cortical excitability. To verify whether cathodal transcranial
      direct current stimulation could reduce the infarct size and the number of
      depolarizations, focal ischemia was induced in the rat by the 3 vessels occlusion
      technique. In the first experiment 12 ischemic rats received cathodal stimulation
      (alternating 15 min on and 15 min off) starting 45 min after middle cerebral
      artery occlusion and lasting 4 h. In the second experiment 12 ischemic rats
      received cathodal transcranial direct current stimulation with the same protocol
      but starting soon after middle cerebral artery occlusion and lasting 6 h. In both
      experiments controls were 12 ischemic rats not receiving stimulation. Cathodal
      stimulation reduced the infarct volume in the first experiment by 20% (p=0.002)
      and in the second by 30% (p=0.003). The area of cerebral infarction was smaller
      in animals receiving cathodal stimulation in both experiments (p=0.005). Cathodal
      stimulation reduced the number of depolarizations (p=0.023) and infarct volume
      correlated with the number of depolarizations (p=0.048). Our findings indicate
      that cathodal transcranial direct current stimulation exert a neuroprotective
      effect in the acute phase of stroke possibly decreasing the number of spreading
      depolarizations. These findings may have translational relevance and open a new
      avenue in neuroprotection of stroke in humans.

PMID- 24857353
TI  - IL1-beta expression in multiple sclerosis.

PMID- 24857354
TI  - Longterm deep brain stimulation withdrawal: clinical stability despite
      electrophysiological instability.
AB  - Deep brain stimulation (DBS) is a powerful treatment option for movement
      disorders, including severe generalised dystonia. After several years of
      treatment, cases have been reported in which DBS has been stopped without any
      deterioration in clinical benefit. This might indicate that DBS can restore
      function in some cases. The mechanism of DBS induced clinical retention effects
      has been addressed before. Here, the question we asked was if such clinical
      stability is reflected at the underlying physiology level or whether there is
      indication to believe that a stand-still of symptoms might be at risk because of
      neurophysiological instability. We recorded patients with pre-intervention life
      threatening or severe genetic dystonia with long lasting clinical benefit when
      turned off DBS. Despite clinical stability, our physiological studies revealed
      large changes in the excitability of excitatory and inhibitory motor circuits in
      the cortex, which exceed normal fluctuation. This discrepancy between instability
      in the motor network physiology caused by removal of DBS and clinical stability
      alerts as it potentially indicates a risk to fail and cause symptoms to return. 

PMID- 24857355
TI  - Delayed intracranial hemorrhage after deep brain stimulation in two Parkinson's
      disease patients.

PMID- 24857356
TI  - An open labeled randomized controlled trial of pregabalin versus amitriptyline in
      chronic low backache.
AB  - BACKGROUND: There is no head on comparison of amitriptyline (AMT) and pregabalin
      (PG) in relieving pain and disability in chronic low backache (CLBA). This
      randomized controlled trial reports the efficacy and safety of AMT and PG in
      CLBA. METHODS: Patients with CLBA, 15-65 years of age without specific cause and
      significant neurological deficit were included. Severity of pain was assessed by
      Visual Analogue Scale (VAS) and disability by Oswestry Disability Index (ODI).
      Patients were followed up at 6 and 14 weeks and their VAS score, ODI and side
      effect were noted. Primary outcome was pain relief (>50% improvement in VAS
      score) at 14 weeks and secondary outcome were reduction in ODI (>20%) and side
      effects. RESULTS: 200 patients with CLBA were randomized to AMT (n=103) and PG
      (n=97) using random numbers. The VAS score and ODI improved significantly
      following AMT and PG at 6 and 14 weeks compared to baseline. The improvement in
      pain (57.3% Vs 39.2%; P=0.01) and disability (65% Vs 49.5%; P=0.03) however was
      more in AMT group. The composite side effects were similar in both groups.
      CONCLUSION: AMT and PG are effective in CLBA but AMT reduced pain and disability
      significantly compared to PG.

PMID- 24857363
TI  - The potential of calcium silicate hydrate as a carrier of ibuprofen.
AB  - Calcium silicate nanostructured materials are promising drug carriers owing to
      their excellent biocompatibility, good bioactivity and high drug-loading
      capacity. In recent years, studies have been carried out on the synthesis of
      calcium silicate hydrate (CSH) nanostructured materials with desirable sizes and
      morphologies and their applications in drug delivery, where very interesting
      results and important insights have been documented. This editorial is not
      intended to offer a comprehensive review on the research on CSH nanostructured
      materials as drug carriers; rather, it presents representative examples: i)
      mesoporous microspheres; ii) ultrathin nanosheets; iii) iron oxide/CSH core/shell
      nanocomposites; and iv) CSH/block copolymer nanocomposites, and important results
      obtained in the study of CSH drug delivery systems for ibuprofen (IBU) as a model
      drug. These results show that the nanostructured CSH materials with specially
      designed architectures as IBU carriers have ultrahigh drug-loading capacity and
      sustainable drug release properties; thus, they are promising drug carriers for
      IBU. In addition, a new drug release kinetics has been found in the
      nanostructured CSH drug delivery systems. Most recently, new insight has been
      gained by tracking the behavior of these drug delivery systems on the molecular
      level using synchrotron-based X-ray spectroscopy. 

PMID- 24857364
TI  - Garlic essential oil protects against obesity-triggered nonalcoholic fatty liver
      disease through modulation of lipid metabolism and oxidative stress.
AB  - This study investigated the protective properties of garlic essential oil (GEO)
      and its major organosulfur component (diallyl disulfide, DADS) against the
      development of nonalcoholic fatty liver disease (NAFLD). C57BL/6J mice were fed a
      normal or high-fat diet (HFD) with/without GEO (25, 50, and 100 mg/kg) or DADS
      (10 and 20 mg/kg) for 12 weeks. GEO and DADS dose-dependently exerted antiobesity
      and antihyperlipidemic effects by reducing HFD-induced body weight gain, adipose
      tissue weight, and serum biochemical parameters. Administration of 50 and 100
      mg/kg GEO and 20 mg/kg DADS significantly decreased the release of pro
      inflammatory cytokines in liver, accompanied by elevated antioxidant capacity via
      inhibition of cytochrome P450 2E1 expression during NAFLD development. The anti
      NAFLD effects of GEO and DADS were mediated through down-regulation of sterol
      regulatory element binding protein-1c, acetyl-CoA carboxylase, fatty acid
      synthase, and 3-hydroxy-3-methylglutaryl-coenzyme A reductase, as well as
      stimulation of peroxisome proliferator-activated receptor alpha and carnitine
      palmitoyltransferase-1. These results demonstrate that GEO and DADS dose
      dependently protected obese mice with long-term HFD-induced NAFLD from lipid
      accumulation, inflammation, and oxidative damage by ameliorating lipid metabolic
      disorders and oxidative stress. The dose of 20 mg/kg DADS was equally as
      effective in preventing NAFLD as 50 mg/kg GEO containing the same amount of DADS,
      which demonstrates that DADS may be the main bioactive component in GEO.

PMID- 24857365
TI  - Four-year longitudinal study of clinical and functional endpoints in sporadic
      inclusion body myositis: implications for therapeutic trials.
AB  - Natural history studies in sporadic inclusion body myositis are of fundamental
      interest for future therapeutic trials. Previous works have demonstrated the
      particular relevance of knee extension strength in the follow-up of this disease.
      This work aimed to extend a preceding natural history over 9 months to a four
      year period. Thirteen patients were assessed using clinical and functional scales
      and dynamometry. Except wrist extension torque and manual muscle testing
      composite score, all the measurements presented a significant decline. The most
      important changes were observed for knee extension and ankle flexion and
      extension. The relative change in knee extension strength correlated with the
      level of strength at baseline. A non-linear correlation was found between 6
      minute walk distance and knee extension strength. This study confirms that knee
      extension strength is particularly relevant to follow patients with sporadic
      inclusion body myositis. It also shows that a strength loss does not have linear
      consequences on motor ability. Finally strength and motor ability are
      complementing each other in the understanding of disease progression. 

PMID- 24857366
TI  - Abnormal distribution of heterogeneous nuclear ribonucleoproteins in sporadic
      inclusion body myositis.
AB  - Previous histopathologic studies of sporadic inclusion body myositis (sIBM)
      identified sarcoplasmic aggregation and myonuclear depletion of the predominantly
      nuclear heterogeneous nuclear ribonucleoprotein (hnRNP) TDP-43 in sIBM myofibers.
      Here, we examined sIBM muscle for abnormalities in two other hnRNPs hnRNPA1 and
      hnRNPA2B1, mutations in which cause multisystem proteinopathy associated with
      rimmed-vacuolar myopathies. Muscle biopsy specimens from 13 patients with sIBM
      and 13 patients without sIBM (dermatomyositis N=3, polymyositis N=3, muscular
      dystrophy N=3, motor neuron disease N=2, non-neuromuscular disease N=2) underwent
      immunohistochemistry for hnRNPA1, hnRNPA2B1, and TDP-43. Muscle transcriptional
      microarray data from 27 patients with sIBM and 12 patients without neuromuscular
      disease was analyzed. Depletion of hnRNPA1 and hnRNPA2B1 was present in 15% and
      7% of sIBM myonuclei, respectively, compared with 1% and 0% of myonuclei in non
      sIBM muscle. Sarcoplasmic aggregates of hnRNPA1 and hnRNPA2B1 distinct from TDP
      43 aggregates were also found in sIBM. hnRNPA1 and hnRNPA2B1, as well as other
      hnRNPs, gene expression was unaltered in sIBM compared to normal muscle. Along
      with TDP-43, other hnRNPs, including hnRNPA1 and hnRNPA2B1, are depleted from
      sIBM myonuclei at the protein but not transcript level. The depletion of multiple
      hnRNPs from sIBM myonuclei together with their sarcoplasmic aggregation suggests
      that one aspect of sIBM pathophysiology may involve abnormal RNA metabolism that
      includes hyperassembly of ribonucleoprotein granules mediated by prion-like
      domains in hnRNPs, evolving into pathological aggregates. 

PMID- 24857367
TI  - Increased expression levels of E-cadherin, cytokeratin 18 and 19 observed in
      preeclampsia were not correlated with disease severity.
AB  - INTRODUCTION: Preeclampsia is a pregnancy-specific disorder and placental
      factor(s) contribute to the pathogenesis of preeclampsia. Turnover of villous
      trophoblast is affected by impaired placental perfusion in preeclampsia.
      Expression and localisation of cadherins and cytokeratins are involved in the
      pathogenesis of preeclampsia. However, studies describing the associations
      between cadherins and cytokeratins in preeclampsia are limited. The aim of this
      study was to investigate the expression of E-cadherin, N-cadherin, cytokeratin 18
      and cytokeratin 19 in placentae from women with preeclampsia in order to
      determine whether their expression differs with disease severity. METHODS: 29
      preeclamptic placentae and 25 normotensive placentae were included in this study.
      The expression of E-cadherin, cytokeratin 18, cytokeratin 19 andN-cadherin was
      quantified by immunohistochemistry and western blotting. RESULTS: E-cadherin,
      cytokeratin 18 and cytokeratin 19 were expressed predominantly in the
      syncytiotrophoblast of the placenta and the expression of E-cadherin, cytokeratin
      18 and cytokeratin 19 was significantly increased in preeclampsia compared to
      normotensive pregnancies. However, there was no significant difference in
      expression between severe preeclampsia and mild preeclampsia. In addition, there
      was no difference in the expression of N-cadherin between preeclampsic and
      normotensive pregnancies. DISCUSSION: Our data demonstrated increased expression
      of E-cadherin, cytokeratin 18 and cytokeratin 19 in the syncytiotrophoblast of
      preeclamptic placentae, but this increase was not correlated with disease
      severity. CONCLUSION: Our data suggests that E-cadherin and cytokeratins are
      involved in the pathogenesis of preeclampsia.

PMID- 24857368
TI  - Serum tumor markers in bile duct cancer--a review.
AB  - CONTEXT: Bile duct cancer (BDC) is a disease with a very grave prognosis, often
      diagnosed too late. OBJECTIVE: The aim of this review is to evaluate available
      literature on tumor markers in serum from patients with BDC. METHODS: Using the
      search words "serum markers", "bile duct cancer", "cholangiocarcinoma",
      "biomarker" and "tumor marker", a search was carried out. RESULTS: Seventy-five
      studies were included in the review. CONCLUSION: CA19-9 is by far the most
      studied and most promising diagnostic and/or prognostic marker in BDC. But also
      the different mucins are interesting as new markers of BDC in serum.

PMID- 24857369
TI  - Chronic autoimmune thyroiditis and thyroid cancer.

PMID- 24857370
TI  - Risk factors for bovine tuberculosis persistence in beef herds of Southern and
      Central Spain.
AB  - In order to assess risk factors related to bovine tuberculosis (bTB) persistence,
      a case-control study, comparing persistent versus transient bTB infected beef
      farms from Central and Southern Spain, was conducted. Farms were matched by herd
      size and geographical location (county). A questionnaire administered by personal
      interview was conducted on 150 herds (80 controls and 70 cases) from Andalucia
      and Castilla La Mancha regions. The questionnaire included questions related to
      the personnel involved in routine diagnostics, structure of the farm and of the
      herd, management, presence of other domestic species and of wildlife reservoirs.
      According to the results of our study, farms with large pasture areas and bTB
      infected neighbors had more difficulties in eradicating the disease, and
      therefore, were more likely to suffer a persistent bTB infection. The odds of bTB
      persistence were between 1.2 and 5.1 (i.e., 95% confidence interval of the OR)
      times higher in those herds that had a neighbor infected herd. Farms with large
      pasture areas had odds between 1.2 and 12.7 (i.e., 95% confidence interval of the
      OR) times higher of having a persistent bTB episode than farms with small pasture
      areas. 

PMID- 24857371
TI  - Inferences about the transmission of Schmallenberg virus within and between
      farms.
AB  - In the summer of 2011 Schmallenberg virus (SBV), a Culicoides-borne
      orthobunyavirus, emerged in Germany and The Netherlands and subsequently spread
      across much of Europe. To draw inferences about the transmission of SBV we have
      developed two models to describe its spread within and between farms. The within
      farm model was fitted to seroprevalence data for cattle and sheep farms in
      Belgium and The Netherlands, with parameters estimated using approximate Bayesian
      computation. Despite the short duration of viraemia in cattle and sheep (mean of
      3-4 days) the within-farm seroprevalence can reach high levels (mean within-herd
      seroprevalence >80%), largely because the probability of transmission from host
      to vector is high (14%) and SBV is able to replicate quickly (0.03 per day
      degree) and at relatively low temperatures (threshold for replication: 12.3
      degrees C). Parameter estimates from the within-farm model were then used in a
      separate between-farm model to simulate the regional spread of SBV. This showed
      that the rapid spread of SBV at a regional level is primarily a consequence of
      the high probability of transmission from host to vector and the temperature
      requirements for virus replication. Our results, obtained for a region of the UK
      in a typical year with regard to animal movements, indicate that there is no need
      to invoke additional transmission mechanisms to explain the observed patterns of
      rapid spread of SBV in Europe. Moreover, the imposition of movement restrictions,
      even a total movement ban, has little effect on the spread of SBV at this scale.

PMID- 24857372
TI  - Hydrogen peroxide formation in a surrogate lung fluid by transition metals and
      quinones present in particulate matter.
AB  - Inhaled ambient particulate matter (PM) causes adverse health effects, possibly
      by generating reactive oxygen species (ROS), including hydrogen peroxide (HOOH),
      in the lung lining fluid. There are conflicting reports in the literature as to
      which chemical components of PM can chemically generate HOOH in lung fluid
      mimics. It is also unclear which redox-active species are most important for HOOH
      formation at concentrations relevant to ambient PM. To address this, we use a
      cell-free, surrogate lung fluid (SLF) to quantify the initial rate of HOOH
      formation from 10 transition metals and 4 quinones commonly identified in PM.
      Copper, 1,2-naphthoquinone, 1,4-naphthoquinone, and phenanthrenequinone all form
      HOOH in a SLF, but only copper and 1,2-naphthoquinone are likely important at
      ambient concentrations. Iron suppresses HOOH formation in laboratory solutions,
      but has a smaller effect in ambient PM extracts, possibly because organic ligands
      in the particles reduce the reactivity of iron. Overall, copper produces the
      majority of HOOH chemically generated from typical ambient PM while 1,2
      naphthoquinone generally makes a small contribution. However, measured rates of
      HOOH formation in ambient particle extracts are lower than rates calculated from
      soluble copper by an average (+/-1sigma) of 44 +/- 22%; this underestimate is
      likely due to either HOOH destruction by Fe or a reduction in Cu reactivity due
      to organic ligands from the PM. 

PMID- 24857374
TI  - Application of COI barcode sequence for the identification of snake medicine
      (Zaocys).
AB  - Counterfeits in the medicine market make the authentication of snakes used for
      Chinese medicine a challenge to Chinese drug regulatory control agencies. This
      paper explores existing methods that can be used to quickly and accurately
      distinguish Zaocys (Z. dhumnades) from its counterfeits for routine
      identification of snake meats in food and drug control laboratories. In this
      research, the Cytochrome Oxidase I (COI) fragments of 51 samples from 17 species
      of snakes were amplified using Polymerase Chain Reaction (PCR) and sequenced. The
      inter- and intra-specific variations of COI sequences were analyzed and compared
      based on Kimura-2-parameter (K-2P) distances; the minimal interspecific K-2P
      distance was 0.0934, which was bigger than the maximum intraspecific K-2P
      distance in Z. dhumnades (0.0523), indicating that Zaocys can be separated from
      its counterfeits. The Neighbor-Joining (N-J) tree of the snakes was constructed
      and the results show that snakes of the same species cluster with 100% bootstrap
      values. Since the Zaocys and its counterfeits are of different species, they can
      be distinguished using the N-J tree method. Another 10 samples of Zaocys from
      markets and drug stores were identified at the species level, among which 5
      samples were proven to be the counterfeits--Ptyas korros.

PMID- 24857373
TI  - Prenatal and postnatal genetic influence on lung function development.
AB  - BACKGROUND: It is unknown to what extent adult lung function genes affect lung
      function development from birth to childhood. OBJECTIVE: Our aim was to study the
      association of candidate genetic variants with neonatal lung function and lung
      function development until age 7 years. METHODS: Lung function measurement by
      means of spirometry with the raised-volume thoracoabdominal compression technique
      and bronchial responsiveness to methacholine challenge were assessed in 411 high
      risk newborns from the Copenhagen Prospective Study on Asthma in Childhood 2000
      (COPSAC2000) cohort. Measures were repeated at age 7 years. Genetic risk scores
      were calculated based on reported single nucleotide polymorphisms for adult lung
      function (FEV1/forced expiratory vital capacity [FVC] ratio and FEV1) as the
      number of risk alleles weighted on known effect size. These genetic risk scores
      were analyzed against lung function measures as z scores at birth (forced
      expiratory volume in 0.5 seconds [FEV0.5], forced expiratory flow at 50% of
      functional vital capacity [FEF50], and provocative dose of methacholine causing a
      15% decrease in lung function [PD15]) and at age 7 years (FEV1, FEF50, and
      provocative dose of methacholine causing a 20% decrease in lung function [PD20])
      and with development from birth to age 7 years (FEV0.5/1, FEF50, and PD15/20).
      RESULTS: The genetic risk scores were not associated with lung function measures
      at age 1 month, but the FEV1/FVC genetic risk score was associated with reduced
      FEF50 values at age 7 years (P = .01) and similarly with reduced growth in FEF50
      from birth to age 7 years (P = .02). This score was also associated with
      increased bronchial responsiveness (reduced PD20) at age 7 years (P = .02) and
      change in responsiveness from birth to age 7 years (P = .05). CONCLUSION: Lung
      function genetic variants identified in adults were not associated with neonatal
      lung function or bronchial responsiveness but with the development of these lung
      function measures during early childhood, suggesting a window of opportunity for
      interventions targeting these genetic mechanisms.

PMID- 24857375
TI  - Mitochondrial genome organization of the Ochre-bellied Flycatcher, Mionectes
      oleagineus.
AB  - We sequenced and compared the mitogenome organization of two specimens of
      suboscine tyrant flycatcher Mionectes oleagineus from western and eastern Panama,
      representing distinct mtDNA clades. These samples show identical gene arrangement
      and vary in size by less than 5 base pairs. Both depict a non-standard avian gene
      order with an extra non-coding region (e.g. the remnant CR2), which differs in
      one base pair between them. Small size differences are also found on the control
      region and the 16S rRNA. Average uncorrected pairwise divergence among protein
      coding genes (PCGs) was 2.8, ranging from 1.9% for COXIII and ND6 to 3.2% for ND2
      and ATP6, respectively. These mitogenomes may be useful for understanding the
      evolutionary dynamics of gene order in bird mitochondrial genomes. 

PMID- 24857376
TI  - Hepatic PPARgamma and LXRalpha independently regulate lipid accumulation in the
      livers of genetically obese mice.
AB  - The nuclear hormone receptors liver X receptor alpha (LXRalpha) and peroxisome
      proliferator-activated receptor gamma (PPARgamma) play key roles in the
      development of fatty liver. To determine the link between hepatic PPARgamma and
      LXRalpha signaling and the development of fatty liver, a LXRalpha-specific
      ligand, T0901317, was administered to normal OB/OB and genetically obese (ob/ob)
      mice lacking hepatic PPARgamma (Ppargamma(DeltaH)). In ob/ob-Ppargamma(DeltaH)
      and OB/OB-Ppargamma(DeltaH) mice, as well as ob/ob-Ppargamma(WT) and OB/OB
      Ppargamma(WT) mice, the liver weights and hepatic triglyceride levels were
      markedly increased in response to T0901317 treatment. These results suggest that
      hepatic PPARgamma and LXRalpha signals independently contribute to the
      development of fatty liver. 

PMID- 24857377
TI  - Phosphorylation of multifunctional nucleolar protein nucleophosmin (NPM1) by
      aurora kinase B is critical for mitotic progression.
AB  - The functional association of NPM1 with Aurora kinases is well documented.
      Surprisingly, although NPM1 is a well characterized phosphoprotein, it is unknown
      whether it is a substrate of Aurora kinases. We have found that Aurora kinases A
      and B can phosphorylate NPM1 at a single serine residue, Ser125, in vitro and in
      vivo. Phosphorylated-S125-NPM1 (pS125-NPM1) localizes to the midbody region
      during late cytokinesis where it colocalizes with Aurora B. The overexpression of
      mutant (S125A) NPM1 resulted in the deregulation of centrosome duplication and
      mitotic defects possibly due to cytokinesis failure. These data suggest that
      Aurora kinase B-mediated phosphorylation of NPM1 plays a critical role during
      mitosis, which could have wider implications in oncogenesis. 

PMID- 24857378
TI  - Post-assembly modification of kinetically metastable Fe(II)2L3 triple helicates.
AB  - We report the covalent post-assembly modification of kinetically metastable amine
      bearing Fe(II)2L3 triple helicates via acylation and azidation. Covalent
      modification of the metastable helicates prevented their reorganization to the
      thermodynamically favored Fe(II)4L4 tetrahedral cages, thus trapping the system
      at the non-equilibrium helicate structure. This functionalization strategy also
      conveniently provides access to a higher-order tris(porphyrinatoruthenium)
      helicate complex that would be difficult to prepare by de novo ligand synthesis. 

PMID- 24857379
TI  - Sentinel node mapping diagnostic studies warrant a unique reporting criteria:
      comment on Xiong et al. systematic review.

PMID- 24857380
TI  - Synchronous lobular carcinoma in situ and invasive lobular cancer: marker or
      precursor for invasive lobular carcinoma.
AB  - AIM: Lobular carcinoma in situ (LCIS) is a known risk factor for invasive breast
      carcinoma, but there is increasing data indicating a possible precursor
      relationship. This study investigates the incidence of lobular carcinoma in situ
      that occurs with invasive lobular carcinoma (ILC). METHODS: Women diagnosed with
      ILC or LCIS from 2000 to 2010 were retrospectively identified and reviewed after
      institutional review board approval. This group was divided into two cohorts: ILC
      alone, and LCIS and ILC (ILC/LCIS). Patient demographics, disease
      characteristics, and treatment modalities were captured. p < 0.05 is considered
      significant. RESULTS: A total of 148 patients with ILC or LCIS were identified.
      Forty-four (54%) patients with only ILC, and 37 (46%) patients with ILC/LCIS were
      identified. Median age at diagnosis was 62 for ILC and 64 years for ILC/LCIS (p =
      0.8). In patients with ILC, total mastectomy was the predominant treatment
      modality in 28 of 44 (64%) patients, while 18 of 37 (49%) patients with ILC/LCIS
      underwent breast conservation therapy (p = 0.3). Median largest tumor diameter
      was 35 mm (range 1-110) for ILC, and 15 mm (range 5-85) for ILC/LCIS (p = 0.03).
      Nodal status was positive in 17 of 39 (44%) ILC and 13 of 34 (38%) ILC/LCIS (p =
      0.6). CONCLUSIONS: The 46% incidence of LCIS associated with ILC in our cohort
      study is similar to that reported for ductal carcinoma in situ identified with
      invasive ductal carcinoma at ~40%. The association of pre-invasive and invasive
      lobular lesions should be further studied in a large scale prospective study to
      assess for a precursor relationship.

PMID- 24857381
TI  - Interventions to prevent postoperative delirium in elderly cancer patients should
      be targeted at those undergoing nonsuperficial surgery with special attention to
      the cognitive impaired patients.
AB  - AIMS: The aim of this study was to determine risk factors for postoperative
      delirium (POD) in elderly cancer patients. METHODS: This study was an
      observational multicentre retrospective study performed in the University Medical
      Center Groningen and Medical Center Leeuwarden, the Netherlands. Patients over 65
      years of age undergoing elective surgery for a solid tumour were included. The
      main outcome was POD. Medical records were screened for POD using a standardized
      instrument. The risk factors considered were: age, gender, severity of the
      surgical procedure, comorbidity, American Society of Anaesthesiologists (ASA)
      score and 15 items suggestive for frailty as measured with the Groningen Frailty
      Indicator (GFI). To examine an association between the risk factors and the
      development of POD, univariate and multivariate logistic regression analysis was
      performed to estimate odds ratios (ORs) and 95% confidence intervals (CIs).
      RESULTS: We reviewed 251 medical records. Forty-six patients developed POD
      (18.3%). Preoperative cognitive functioning (as measured by the item cognition of
      the GFI) (OR: 23.36; 95% CI: 5.33-102.36) and severity of the surgical procedure
      were identified as independent risk factors for POD; intermediate (OR: 15.44, 95%
      CI: 1.70-140.18) and major surgical procedures (OR: 45.01, 95% CI: 5.22-387.87)
      significantly increased the risk for POD as compared to minor surgery.
      CONCLUSIONS: Preoperative cognitive functioning and the severity of the surgical
      procedure are independent risk factors for POD in elderly undergoing elective
      surgery for a solid tumour.

PMID- 24857382
TI  - Optical segmentation of unprocessed breast tissue for margin assessment.
AB  - Visual and tactual examination of unprocessed breast specimens is the standard
      for intraoperative surgical margin assessment in the United States. However, this
      procedure does not provide surgeons or pathologists with microscopic views of the
      tissue, which makes it difficult to accurately assess margin status or the extent
      of the disease, especially in non-palpable cases. We use a combination of
      spectral and polarization macroscopic imaging to optically segment the adipose
      and collagen tissues thus highlighting regions suspected of containing epithelium
      in order to facilitate optical microscopy techniques. A small study on five
      lumpectomy and mastectomy samples showed a sensitivity of 70% +/- 20% and
      specificity of 50% +/- 10% for adipose segmentation and a sensitivity of 50% +/-
      20% and specificity of 50% +/- 20% for collagen segmentation. This sensitivity
      and specificity are sufficient for providing morphological information to the
      pathologist in order to guide microscopic examination of regions likely to be of
      clinical significance.

PMID- 24857383
TI  - Vacuolar H+-ATPase is down-regulated by the angiogenesis-inhibitory pigment
      epithelium-derived factor in metastatic prostate cancer cells.
AB  - The Vacuolar H+-ATPases (V-ATPases), a multi-subunits nanomotor present in all
      eukaryotic cells resides in the endomembranes of exocytotic and endocytotic
      pathways. Plasmalemmal V-ATPases have been shown to be involved in tumor cell
      metastasis. Pigment epithelium-derived factor (PEDF), a potent endogenous
      inhibitor of angiogenesis, is down-regulated in prostate cancer cells. We
      hypothesized that the transduction of PEDF in prostate cancer cells will down
      regulate V-ATPase function; that in turn will decrease the expression of the V
      ATPase accessory protein ATP6ap2 and a-subunit isoforms that target V-ATPase to
      the cell surface. To test these hypotheses, we used the human androgen-sensitive
      prostate cancer cells LNCaP, and its castration-refractory-derivative CL1 that
      were engineered to stably co-express the DsRed Express Fluorescent Protein with
      or without PEDF. To determine if PEDF down-regulates the function of V-ATPase, we
      measured the rate of proton fluxes (JH+) of the cytosolic and endosome/lysosome
      compartments. The mRNA levels for subunit-a isoforms and the ATP6ap2 were
      measured using quantitative reverse transcription-PCR. The results showed that
      PEDF expression decreased the rate of JH+ in metastatic CL1 cells without
      affecting JH+ in non-metastatic LNCaP cells, when studying pH(cyt).
      Interestingly, PEDF did not affect JH+ in endosomes/lysosomes either in
      metastatic cells or in non-metastatic cells. We also showed that PEDF
      significantly decreases the levels of a4 isoform and ATP6ap2 in metastatic CL1
      cells, without affecting the levels of a4 isoform in the non-metastatic LNCaP
      cells. These data identify PEDF as a novel regulator of V-ATPase suggesting a new
      way by which PEDF may inhibit prostate tumor growth.

PMID- 24857384
TI  - The use of 2D and 3D information in a perceptual-cognitive judgement task.
AB  - We examined whether the use of three-dimensional (3D) simulations in an off-field
      offside decision-making task is beneficial compared to the more widely available
      two-dimensional (2D) simulations. Thirty-three assistant referees, who were all
      involved in professional football, participated in the experiment. They assessed
      40 offside situations in both 2D and 3D formats using a counterbalanced design. A
      distinction was made between offside situations near (i.e., 15 m) and far (i.e.,
      30 m) from the touchline. Subsequently, a frame recognition task was performed in
      which assistant referees were asked to indicate which of the five pictures
      represented the previous video scene. A higher response accuracy score was
      observed under 3D (80.0%) compared to 2D (75.0%) conditions, in particular for
      the situations near the touchline (3D: 81.8%; 2D: 72.7%). No differences were
      reported between 2D and 3D in the frame recognition task. Findings suggest that
      in highly dynamic and complex situations, the visual system can benefit from the
      availability of 3D information, especially for relatively fine, metric position
      judgements. In the memory task, in which a mental abstraction had to be made from
      a dynamic situation to a static snapshot, 3D stereo disparities do not add
      anything over and beyond 2D simulations. The specific task demands should be
      taken into account when considering the most appropriate format for testing and
      training.

PMID- 24857385
TI  - Decreased levels of serum nesfatin-1 in patients with preeclampsia.
AB  - CONTEXT: Nesfatin-1 is implicated to possess an anti-inflammatory effect.
      OBJECTIVE: The aim of our study is to investigate whether abnormal serum levels
      of nesfatin-1 are associated with the presence and severity of preeclampsia.
      METHODS: A total of 120 women with preeclampsia and 92 women with uncomplicated
      pregnancies were enrolled in this study. RESULTS: Women with preeclampsia showed
      significantly reduced levels of serum nesfatin-1 levels than women with
      uncomplicated pregnancies. Serum nesfatin-1 levels were significantly decreased
      in women with severe preeclampsia compared with women with mild preeclampsia.
      CONCLUSION: Decreased serum nesfatin-1 levels are associated with the presence
      and severity of preeclampsia.

PMID- 24857386
TI  - The role of behavior change in antimicrobial stewardship.
AB  - Emerging evidence suggests that antimicrobial prescribing behaviors are
      influenced by local culture and a prescribing etiquette that is abided by all
      health care professionals. Local cultural unspoken rules often play a more
      pivotal role than the recommendations of guidelines and policies drawn up by
      experts in influencing antimicrobial prescribing. It is important to recognize
      the key drivers of prescribing behaviors and the incentives to alter behaviors
      and to incorporate these into stewardship programs. This review summarizes key
      concepts in behavior change in antimicrobial prescribing and the gaps that exist
      in addressing behavior change in this field. 

PMID- 24857387
TI  - Health care provider education as a tool to enhance antibiotic stewardship
      practices.
AB  - Antibiotic stewardship education for health care providers provides a foundation
      of knowledge and an environment that facilitates and supports optimal antibiotic
      prescribing. There is a need to extend this education to medical students and
      health care trainees. Education using passive techniques is modestly effective
      for increasing prescriber knowledge, whereas education using active techniques is
      more effective for changing prescribing behavior. Such education has been shown
      to enhance other antibiotic stewardship interventions. In this review, the need
      and suggested audience for antibiotic stewardship education are highlighted, and
      effective education techniques are recommended for increasing knowledge of
      antibiotics and improving their use. 

PMID- 24857388
TI  - Antimicrobial use metrics and benchmarking to improve stewardship outcomes:
      methodology, opportunities, and challenges.
AB  - Measurement of antimicrobial use before and after an intervention and the
      associated outcomes are key activities of antimicrobial stewardship programs. In
      the United States, the recommended metric for aggregate antibiotic use is days of
      therapy/1000 patient-days. Clinical outcomes, including response to therapy and
      bacterial resistance, are critical measures but are more difficult to document
      than economic outcomes. Interhospital benchmarking of risk adjusted antimicrobial
      use is possible, although several obstacles remain before it can have an impact
      on patient care. Many challenges for stewardship programs remain, but the methods
      and science to support their efforts are rapidly evolving. 

PMID- 24857389
TI  - The role of the microbiology laboratory in antimicrobial stewardship programs.
AB  - One of the impediments to the success of antimicrobial stewardship is the lack of
      availability of rapid and sensitive laboratory tests. The last decade has seen an
      explosion in new technologies that permit, in less than 4 hours, the
      identification of organisms and their resistance markers. In addition, the use of
      biomarkers has been explored in algorithms to distinguish infections that require
      antimicrobial agents. Clinical microbiology laboratories also contribute to the
      success of stewardship programs through compilation of aggregate antimicrobial
      susceptibility data. This article reviews rapid diagnostics, the use of
      biomarkers, and antibiogram development to antimicrobial stewardship activities
      and the subsequent impact on patient outcomes.

PMID- 24857390
TI  - Antimicrobial stewardship in long-term care facilities.
AB  - Although antimicrobial stewardship has been shown to improve microbiologic
      susceptibility patterns, decrease drug toxicities, and lower overall drug costs
      in the inpatient setting, there are few studies assessing programs in the long
      term care (LTC) setting. Implementing antimicrobial stewardship programs in LTC
      settings can be challenging as the LTC setting houses a unique population of
      frail and older adults with several preexisting conditions and multiple risk
      factors for colonization with multidrug-resistant organisms. Antimicrobial
      stewardship has an important role in decreasing inappropriate antibiotic use,
      encouraging targeted treatment of specific disease states, and limiting the
      untoward effects and costs of antimicrobials in this vulnerable population. 

PMID- 24857391
TI  - Antimicrobial stewardship in the NICU.
AB  - There are unique challenges to antimicrobial stewardship in neonatal intensive
      care units (NICUs). Diagnosis of infection is difficult as neonates can have
      nonspecific signs and symptoms. Between and within NICUs, significant variation
      exists in the treatment duration of suspected sepsis and pneumonia. Development
      of multidisciplinary teams and meaningful metrics are essential for sustainable
      antibiotic stewardship. Potential stewardship interventions include optimizing
      culturing techniques, guiding empiric therapy by NICU-specific antibiograms,
      using ancillary laboratory tests, and promptly discontinuing therapy once
      infection is no longer suspected. Use of large neonatal databases can be used to
      benchmark antibiotic use and conduct comparative effectiveness research. 

PMID- 24857392
TI  - Antimicrobial stewardship in immunocompromised hosts.
AB  - The global spread of antimicrobial resistance has limited the availability of
      antimicrobial agents to treat infections that affect immunocompromised hosts.
      Efforts to optimize the selection, dosing, and duration of antimicrobial therapy
      to improve patient outcomes and minimize selective pressure on antimicrobial
      resistance are relevant to immunocompromised patients. Collaborative efforts
      between health care providers with expertise in the diagnosis and treatment of
      patients with various degrees of immunosuppression are pivotal for the success of
      antimicrobial stewardship programs in immunocompromised patients. 

PMID- 24857393
TI  - Hospital antimicrobial stewardship in the nonuniversity setting.
AB  - Inappropriate antimicrobial use and antimicrobial resistance persist across the
      healthcare continuum. Antimicrobial stewardship guidelines assist healthcare
      institutions in establishing antimicrobial stewardship programs but rely on
      infectious diseases expertise and leadership, which are not available in all
      settings. Despite this, many institutions have found ways to use available
      resources to perform stewardship activities, with improvements in antimicrobial
      use and reductions in resistance and cost. This article highlights success
      stories in nonuniversity hospital settings and proposes antimicrobial stewardship
      strategies that may be more feasible in settings with limited infectious diseases
      expertise, information technology, or financial resources. 

PMID- 24857394
TI  - Transformation of antimicrobial stewardship programs through technology and
      informatics.
AB  - The successful integration of technology in antimicrobial stewardship programs
      has made it possible for clinicians to function more efficiently. With government
      endorsement of electronic health records (EHRs), EHRs and clinical decision
      support systems (CDSSs) are being used as decision support tools to aid
      clinicians in efforts to improve antibiotic use. Likewise, medical applications
      (apps) have provided educational tools easily accessible to clinicians through
      their mobile devices. In this article, the impact that informatics and technology
      have had on promoting antibiotic stewardship is described, focusing on EHRs and
      CDSSs, apps, electronic resources, and social media. 

PMID- 24857396
TI  - Infectious Disease Clinics of North America. Antimicrobial stewardship. Preface.

PMID- 24857395
TI  - Antimicrobial stewardship interventions: thinking inside and outside the box.
AB  - At present, less than half of all acute health care facilities have antimicrobial
      stewardship programs. By targeting areas that are vulnerable to inappropriate
      antimicrobial use and by using novel strategies to increase the reach of
      stewardship interventions, providers can make antimicrobial stewardship a
      universal practice in all health care settings. This review discusses how
      stewardship can make large impacts in areas where it has traditionally been
      absent in facilities both with and without formal antimicrobial stewardship
      programs. 

PMID- 24857397
TI  - Effects of levothyroxine on growth hormone (gh) sensitivity in children with
      idiopathic short stature.
AB  - BACKGROUND: The possible relationship between the circulating concentrations of
      T4 and GH sensitivity has not been elucidated. OBJECTIVE: The aim of this study
      is to evaluate the effect of levothyroxine supplementation on GH sensitivity in
      prepubertal boys with idiopathic short stature (ISS). METHODS: We selected 28
      prepubertal boys with ISS (mean age 8.2+/-0.5years) and free T4 (Ft4)
      concentrations between the 3rd and the 25th percentiles (Ft4: 0.8-1.5ng/dl). They
      were randomly divided into two groups: Group A received thyroid supplementation
      (1-3MUg/kg/day) for 120days, and Group B received placebo for the same period. To
      evaluate GH sensitivity, an IGF-I generation test (GH: 33MUg/kg/day sc for 3days)
      was performed in both groups: under basal conditions, and after 120days of
      levothyroxine supplementation (or placebo). RESULTS: After thyroid
      supplementation, Group A had higher Ft4 concentrations compared with Group B
      (2.14+/-0.06 vs 1.48+/-0.06ng/dl, p=0.01), their growth velocity was
      significantly higher (2.3+/-0.1 vs 1.5+/-0.2cm/4months), and they exhibited a
      greater increase in IGF-I after GH administration (Group A: 32.5+/-3.8% vs Group
      B 17.3+/-2.6%). CONCLUSION: Supplementation with levothyroxine for 120days
      promotes an increase in growth velocity, and a greater IGF-I response to short
      term GH administration in prepubertal boys with ISS and low-normal thyroid
      hormone concentrations.

PMID- 24857398
TI  - Activation of DREAM (downstream regulatory element antagonistic modulator), a
      calcium-binding protein, reduces L-DOPA-induced dyskinesias in mice.
AB  - BACKGROUND: Previous studies have implicated the cyclic adenosine
      monophosphate/protein kinase A pathway as well as FosB and dynorphin-B expression
      mediated by dopamine D1 receptor stimulation in the development of 3,4
      dihydroxyphenyl-L-alanine (L-DOPA)-induced dyskinesia. The magnitude of these
      molecular changes correlates with the intensity of dyskinesias. The calcium
      binding protein downstream regulatory element antagonistic modulator (DREAM)
      binds to regulatory element sites called DRE in the DNA and represses
      transcription of target genes such as c-fos, fos-related antigen-2 (fra-2), and
      prodynorphin. This repression is released by calcium and protein kinase A
      activation. Dominant-active DREAM transgenic mice (daDREAM) and DREAM knockout
      mice (DREAM(-/-)) were used to define the involvement of DREAM in dyskinesias.
      METHODS: Dyskinesias were evaluated twice a week in mice with 6-hydroxydopamine
      lesions during long-term L-DOPA (25 mg/kg) treatment. The impact of DREAM on L
      DOPA efficacy was evaluated using the rotarod and the cylinder test after the
      establishment of dyskinesia and the molecular changes by immunohistochemistry and
      Western blot. RESULTS: In daDREAM mice, L-DOPA-induced dyskinesia was decreased
      throughout the entire treatment. In correlation with these behavioral results,
      daDREAM mice showed a decrease in FosB, phosphoacetylated histone H3, dynorphin
      B, and phosphorylated glutamate receptor subunit, type 1 expression. Conversely,
      genetic inactivation of DREAM potentiated the intensity of dyskinesia, and DREAM(
      /-) mice exhibited an increase in expression of molecular markers associated with
      dyskinesias. The DREAM modifications did not affect the kinetic profile or
      antiparkinsonian efficacy of L-DOPA therapy. CONCLUSIONS: The protein DREAM
      decreases development of L-DOPA-induced dyskinesia in mice and reduces L-DOPA
      induced expression of FosB, phosphoacetylated histone H3, and dynorphin-B in the
      striatum. These data suggest that therapeutic approaches that activate DREAM may
      be useful to alleviate L-DOPA-induced dyskinesia without interfering with the
      therapeutic motor effects of L-DOPA.

PMID- 24857399
TI  - [Successful weaning and extubation in the premature newborn using neurally
      adjusted ventilatory assist].
AB  - Invasive and non-invasive ventilation of the preterm newborn may be associated
      with local and systemic complications due to mechanical trauma to lung tissues
      and their inflammatory response. A key objective of any type of mechanical
      ventilation, therefore, is to reduce its duration and the side effects related to
      it. Neurally Adjusted Ventilatory Assist (NAVA) may improve synchronization
      between patient and ventilator and optimize the gas volume delivered to the
      lungs, according to the patient needs, eventually reducing volu- and biotrauma.
      Two preterm babies with severe respiratory distress syndrome are presented, who
      were successfully weaned and extubated with the help of this ventilatory system.
      Further studies are needed to assess whether short-term benefits are reflected in
      better outcomes in the long run.

PMID- 24857400
TI  - The cost-effectiveness ratio of a managed protocol for severe sepsis.
AB  - PURPOSE: Severe sepsis is a time-dependent disease, and implementation of early
      treatment has been associated with mortality rate reduction. However, the
      literature is controversial regarding cost-effectiveness analysis of this
      intervention. The aim was to assess the cost-effectiveness of a managed protocol
      for the treatment of severe sepsis. MATERIALS AND METHODS: This is a prospective
      cohort study involving a historical comparison (before and after the
      implementation of the protocol) of patients who had been hospitalized with severe
      sepsis and septic shock. The group of patients who were treated before the
      assistance routine was implemented was considered to be the control. The case
      managed nurse involved with assistance protocol performed the data collection.
      This nurse received special training to ensure the quality of the data and to
      measure the intervention throughout the implementation process. RESULTS: A total
      of 414 patients were analyzed. The mortality rates were 57% in the control group
      and 38% in the protocol group (P=.002). After the implementation of the protocol,
      the absolute risk reduction was 18%; and the relative risk reduction was 31.8%.
      There was a tendency for a reduction in the cost of the full hospitalization, but
      this trend did not reach statistical significance. Nevertheless, the cost of
      hospitalization in the intensive care unit was reduced significantly from US
      $138,237+/-$202,418 in the control group to US $85,484+/-$127,471 in the protocol
      group (P=.003). The managed protocol for sepsis resulted in an average gain of
      3.2 life-years after being discharged from the hospital (8.8+/-13.3 years in the
      control group and 12.0+/-14.0 years in the protocol group, P=.01). CONCLUSIONS:
      Given that the incremental cost was lower than or equal to zero, the
      effectiveness of the protocol was justified by the significant increase in the
      life-years saved and the reduced mortality.

PMID- 24857401
TI  - Respiratory rate at intensive care unit discharge after liver transplant is an
      independent risk factor for intensive care unit readmission within the same
      hospital stay: a nested case-control study.
AB  - PURPOSE: Intensive care unit (ICU) readmission negatively impacts patients'
      outcomes. We aimed to characterize and determine risk factors for ICU readmission
      within the initial hospital stay after liver transplant (LT). MATERIALS AND
      METHODS: The reference cohort included 369 LT recipients from a Canadian center
      between 2005 and 2012. One control was randomly selected per each case of ICU
      readmission within the initial hospital stay after LT. Survival analysis used the
      Kaplan-Meier method. Associations were studied by conditional logistic
      regression. RESULTS: Fifty-two (14%) LT recipients were readmitted to the ICU
      within the initial hospital stay after LT; they had longer first hospital stay (P
      < .001) and lower 1-month to 2-year cumulative survival (P < .001). Respiratory
      failure was the major cause of ICU readmission (61%). Respiratory rate at
      discharge from the first ICU stay after LT was an independent risk factor for ICU
      readmission (odds ratio = 1.24). The cutoff point more than 20 breaths per minute
      prognosticated ICU readmission with a specificity of 90% and a positive
      predictive value of 80%. CONCLUSIONS: Intensive care unit readmission within the
      initial hospital stay after LT negatively impacts LT recipients' outcomes.
      Monitoring respiratory rate at discharge from the first ICU stay after LT is
      important to prevent readmission.

PMID- 24857402
TI  - A systematic review, psychometric analysis and qualitative assessment of generic
      preference-based measures of health in mental health populations and the
      estimation of mapping functions from widely used specific measures.
AB  - BACKGROUND: Generic preference-based measures of health like the EQ-5D and SF
      6D((r)) are increasingly being used in economic evaluation and outcome
      assessment. However, there are concerns as to whether or not these generic
      measures are appropriate for use in people with mental health problems.
      OBJECTIVES: The EQ-5D and SF-36((r)) (including its derivatives the SF-12((r))
      and SF-6D) were assessed using the psychometric criteria of validity and
      responsiveness using quantitative and qualitative methods. Another aim was to
      estimate mapping functions between the EQ-5D and SF-6D and condition-specific
      measures, where appropriate. DESIGN: Four studies were undertaken to examine the
      appropriateness of the measures: (1) a systematic review of quantitative evidence
      on validity and responsiveness; (2) a further quantitative assessment of these
      criteria using existing data sets; (3) a review of qualitative research on the
      quality of life of people with mental health problems; and (4) qualitative
      semistructured interviews of people with a full range of problems. A fifth study
      estimated mapping functions between mental health-specific measures and the EQ-5D
      and SF-6D. SETTING: A choice of venue was offered for the interviews including
      the participant's own home, a room at the university or a centre frequently used
      by mental health services. PARTICIPANTS: The interviews were undertaken with 19
      people with a broad range of mental health problems at varying levels of
      severity. MAIN OUTCOME MEASURES: The reviews included the EQ-5D and SF-36 (and
      the SF-12 and SF-6D). The psychometric analysis included the Hospital Anxiety and
      Depression Scale (HADS), Clinical Outcomes in Routine Evaluation - Outcome
      Measure (CORE-OM), Generalised Anxiety Disorder Assessment (GAD-7), General
      Health Questionnaire (GHQ-12) and Patient Health Questionnaire (PHQ-9). RESULTS:
      (1) and (2) The EQ-5D and SF-36 achieved an adequate level of performance in
      depression, and to some extent in anxiety and personality disorder. Results from
      the psychometric analyses in schizophrenia and bipolar disorder have been more
      mixed. (3) A framework analysis of 13 studies identified six major themes. (4)
      The interview data fitted the themes from the review well and resulted in minor
      modifications to the themes. The final set of themes comprised: well-being and
      ill-being; control, autonomy and choice; self-perception; belonging; activity;
      hope and hopelessness; and physical health. CONCLUSIONS: The EQ-5D and SF-36
      achieved mixed results in the quantitative testing against psychometric criteria.
      The qualitative analysis suggests this is because they provide a very limited
      coverage of themes identified by people with mental health problems.
      Recommendations for future work include the development of new preference-based
      measures in mental health that are based on, or substantially revise, an existing
      measure. FUNDING: The Medical Research Council.

PMID- 24857403
TI  - Isomerase-catalyzed binding of interleukin-1 receptor-associated kinase 1 to the
      EVH1 domain of vasodilator-stimulated phosphoprotein.
AB  - Interleukin-1 receptor-associated kinase 1 (IRAK1) is a crucial signaling kinase
      in the immune system, involved in Toll-like receptor signaling. Vasodilator
      stimulated phosphoprotein (VASP) is a central player in cell migration that
      regulates actin polymerization and connects signaling events to cytoskeletal
      remodeling. A VASP-IRAK1 interaction is thought to be important in controlling
      macrophage migration in response to protein kinase C-epsilon activation. We show
      that the monomeric VASP EVH1 domain directly binds to the 168WPPPP172 motif in
      the IRAK1 undefined domain (IRAK1-UD) with moderate affinity (KDApp = 203 +/- 3
      MUM). We further show that this motif adopts distinct cis and trans isomers for
      the Trp168-Pro169 peptide bond with nearly equal populations, and that binding to
      the VASP EVH1 domain is specific for the trans isomer, coupling binding to
      isomerization. Nuclear magnetic resonance line shape analysis and tryptophan
      fluorescence experiments reveal the complete kinetics and thermodynamics of the
      binding reaction, showing diffusion-limited binding to the trans isomer followed
      by slow, isomerization-dependent binding. We further demonstrate that the
      peptidyl-prolyl isomerase cyclophilin A (CypA) catalyzes isomerization of the
      Trp168-Pro169 peptide bond and accelerates binding of the IRAK1-UD to the VASP
      EVH1 domain. We propose that binding of IRAK1 to tetrameric VASP is regulated by
      avidity through the assembly of IRAK1 onto receptor-anchored signaling complexes
      and that an isomerase such as CypA may modulate IRAK1 signaling in vivo. These
      studies demonstrate a direct interaction between IRAK1 and VASP and suggest a
      potential mechanism for how this interaction might be regulated by both assembly
      of IRAK1 onto an activated signaling complex and PPIase enzymes.

PMID- 24857404
TI  - Combined use of ascorbic acid and cyanocobalamin in clearance of Trypanosoma
      cruzi.

PMID- 24857405
TI  - What roles do errors serve in motor skill learning? An examination of two
      theoretical predictions.
AB  - Easy-to-difficult and difficult-to-easy progressions of task difficulty during
      skill acquisition were examined in 2 experiments that assessed retention, dual
      task, and transfer tests of learning. Findings of the first experiment suggest
      that an easy-to difficult progression did not consistently induce implicit
      learning processes and was not consistently beneficial to performance under a
      secondary-task load. The findings of experiment two did not support the
      predictions made based on schema theory and only partially supported predictions
      based on reinvestment theory. The authors interpret these findings to suggest
      that the timing of error in relation to the difficulty of the task (functional
      task difficulty) plays a role in the transfer of learning to novel versions of a
      task.

PMID- 24857406
TI  - Shell-engineered chiroplasmonic assemblies of nanoparticles for zeptomolar DNA
      detection.
AB  - DNA-bridged pairs of seemingly spherical metallic nanoparticles (NPs) have chiral
      geometry due to the nonideal oblong shape of the particles and scissor-like
      conformation. Here we demonstrate that deposition of gold and silver shells
      around the NP heterodimers enables spectral modulation of their chiroplasmonic
      bands in 400-600 nm region and results in significantly enhanced optical activity
      with g-factors reaching 1.21 * 10(-2). The multimetal heterodimers optimized for
      coupling with the spin angular momentum of incident photons enable polymerase
      chain reaction (PCR)-based DNA detection at the zeptomolar level. This
      significant improvement in the sensitivity of detection is attributed to
      improvement of base pairing in the presence of NPs, low background for
      chiroplasmonic detection protocol, and enhancement of photon-plasmon coupling for
      light with helicity matching that of the twisted geometry of the heterodimers. 

PMID- 24857407
TI  - Understanding pathologic variants of renal cell carcinoma: distilling therapeutic
      opportunities from biologic complexity.
AB  - CONTEXT: Once believed to represent a uniform malignant phenotype, renal cell
      carcinoma (RCC) is now viewed as a diverse group of cancers that arise from the
      nephron. OBJECTIVE: To review the pathologic characteristics, clinical behavior,
      molecular biology, and systemic therapy options of recognized RCC histologic
      subtypes. EVIDENCE ACQUISITION: A systematic review of English-language articles
      was performed using the Medline and Web of Science databases. Manuscripts were
      selected with consensus of the coauthors and evaluated using the Preferred
      Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) criteria.
      EVIDENCE SYNTHESIS: The major findings of the evaluated manuscripts are discussed
      with an emphasis on the description of the pathologic features, clinical
      behavior, prognosis, and therapeutic strategies. CONCLUSIONS: Classification
      schemes for kidney cancer have undergone dramatic changes over the past two
      decades. Improvements in these classification schemes are important, as
      pathologic variants differ not only in disease biology, but also in clinical
      behavior, prognosis, and response to systemic therapy. In the era of genomic
      medicine, further refinements in characterization of RCC subtypes will be
      critical to the progress of this burgeoning clinical space. PATIENT SUMMARY:
      Kidney cancer can be subdivided into related but different cancers that arise
      from the kidney's tubules. In this article we review current classifications for
      kidney cancer, discuss their characteristics, and provide an overview of each
      subtype's clinical behavior and treatment. We stress that each subtype harbors
      unique biology and thus responds differently to available treatment strategies.

PMID- 24857408
TI  - Dietary protein in urea cycle defects: How much? Which? How?
AB  - Dietary recommendations for patients with urea cycle disorders (UCDs) are
      designed to prevent metabolic decompensation (primarily hyperammonaemia), and to
      enable normal growth. They are based on the 'recommended daily intake'
      guidelines, on theoretical considerations and on local experience. A
      retrospective dietary review of 28 patients with UCDs in good metabolic control,
      at different ages, indicates that most patients can tolerate a natural protein
      intake that is compatible with metabolic stability and good growth. However,
      protein aversion presents a problem in many patients, leading to poor compliance
      with the prescribed daily protein intake. These patients are at risk of chronic
      protein deficiency. Failing to recognise this risk, and further restricting
      protein intake because of persistent hyperammonaemia may aggravate the deficiency
      and potentially lead to episodes of metabolic decompensation for which no clear
      cause is found. These patients may need on-going supplementation with essential
      amino acids (EAA) to prevent protein malnutrition. Current recommendations for
      the management of acute metabolic decompensation include cessation of protein
      intake whilst increasing energy (calorie) intake in the first 24h. We have found
      that plasma concentrations of all EAA are low at the time of admission to
      hospital for metabolic decompensation, with correlation between low EAA
      concentrations, particularly branched-chain amino acids, and hyperammonaemia.
      Thus, supplementation with EAA should be considered at times of metabolic
      decompensation. Finally, it would be advantageous to treat patients in metabolic
      decompensation through enteral supplementation, whenever possible, because of the
      contribution of the splanchnic (portal-drained viscera) system to protein
      retention and metabolism. 

PMID- 24857409
TI  - A re-evaluation of life-long severe galactose restriction for the nutrition
      management of classic galactosemia.
AB  - The galactose-restricted diet is life-saving for infants with classic
      galactosemia. However, the benefit and extent of dietary galactose restriction
      required after infancy remain unclear and variation exists in practice. There is
      a need for evidence-based recommendations to better standardize treatment for
      this disorder. This paper reviews the association between diet treatment and
      outcomes in classic galactosemia and evaluates the contribution of food sources
      of free galactose in the diet. Recommendations include allowing all fruits,
      vegetables, legumes, soy products that are not fermented, various aged cheeses
      and foods containing caseinates. Further research directions are discussed. 

PMID- 24857410
TI  - Systemic accumulation of undigested lysosomal metabolites in an autopsy case of
      mucolipidosis type II; autophagic dysfunction in cardiomyocyte.
AB  - Mucolipidosis type II is an autosomal recessive lysosomal storage disease caused
      by N-acetylglucosamine-1-phosphotransferese deficiency. We report here
      pathological findings of an autopsy case of mucolipidosis type II. The patient
      was an 8-year-old boy with mucolipidosis type II and was complicated with
      hypertrophic cardiomyopathy. He suddenly developed progressive respiratory
      failure and finally died. At autopsy, systemic accumulation of undigested
      lysosomal metabolites was prominent, particularly in the heart, lungs, and dorsal
      root ganglion. In cardiomyocyte, LC3, an autophagy marker, was positive in the
      cytoplasm. Ubiquitin, p62, K48 polyubiquitin, and K63 polyubiquitin were also
      positive in the cytoplasm. Our findings suggest that autophagic dysfunction might
      be associated with the cardiomyopahty of mucolipidosis type II. 

PMID- 24857413
TI  - Non-cytotoxic antifungal agents: isolation and structures of gageopeptides A-D
      from a Bacillus strain 109GGC020.
AB  - Antifungal resistance and toxicity problems of conventional fungicides
      highlighted the requirement of search for new safe antifungal agents. To comply
      with the requirement, we discovered four new non-cytotoxic lipopeptides,
      gageopeptides A-D, 1-4, from a marine-derived bacterium Bacillus subtilis. The
      structures and stereochemistry of gageopeptides were determined by NMR data
      analysis and chemical means. Gageopeptides exhibited significant antifungal
      activities against pathogenic fungi Rhizoctonia solani, Botrytis cinerea, and
      Colletotrichum acutatum with minimum inhibitory concentration (MIC) values of
      0.02-0.06 MUM. In addition, these lipopeptides showed significant motility
      inhibition and lytic activities against zoospores of the late blight pathogen
      Phytophthora capsici. These compounds also showed potent antimicrobial activity
      against Gram positive and Gram negative bacteria with MIC values of 0.04-0.08
      MUM. However, gageopeptides A-D did not exhibit any cytotoxicity (GI50 > 25 MUM)
      against cancer cell lines in sulforhodamine B (SRB), 3-[4,5-dimethylthiazol-2-yl]
      2,5-diphenyltetrazolium bromide (MTT), and WST-1 ((4-[3-4-iodophenyl]-2-(4
      nitrophenyl)-2H-5-tetrazolio)-1,3-benzene disulfonate)) assays, demonstrating
      that these compounds could be promising candidates for the development of non
      cytotoxic antifungal agents. 

PMID- 24857411
TI  - Rapid metagenomic diagnostics for suspected outbreak of severe pneumonia.

PMID- 24857414
TI  - The development of a clinical practice guideline to improve sleep in intensive
      care patients: a solution focused approach.
AB  - OBJECTIVE: Our objective was to develop a guideline to improve the opportunity
      for intensive care patients to rest and sleep. DESIGN AND SETTING: A pragmatic
      solution focused approach to guideline development and implementation was used in
      which data from international literature and original research from the study ICU
      were appraised in extensive consultation with intensive care staff. Audits were
      conducted early in the implementation phase to measure adoption rates. RESULTS:
      Over 320 suggestions were made for inclusion in a practice guideline. Information
      was integrated to create the guideline. A comprehensive 'rest and sleep for the
      intensive care patient' guideline was developed comprising two main themes:
      'Optimise the environment' (for example, 'Quiet conversation') and 'Rest and
      sleep interventions' (for example, 'Provide optimal conditions for night-time
      sleep'). Audit data suggested that adoption of the guideline had begun but was
      not yet embedded in practice. CONCLUSION: The solution focused approach to
      addressing improvements ICU patients' sleep and the consideration of multiple
      sources of evidence resulted in the development of a comprehensive, context
      specific guideline. The process, based on a solution focus, may overcome
      difficulties faced by clinicians endeavouring to improve health care when there
      is a lack of high level evidence.

PMID- 24857415
TI  - Expression profile of hypothalamic neuropeptides in chicken lines selected for
      high or low residual feed intake.
AB  - The R(+) and R(-) chicken lines have been divergently selected for high (R(+)) or
      low (R(-)) residual feed intake. For the same body weight and egg production, the
      R(+) chickens consume 40% more food than their counterparts R(-) lines. In the
      present study we sought to determine the hypothalamic expression profile of
      feeding-related neuropeptides in these lines maintained under fed or food
      deprived conditions. In the fed condition, the suppressor of cytokine signaling 3
      (SOCS3) was 17-fold lower (P<0.05) and the ghrelin receptor was 7-fold higher
      (P<0.05) in R(+) compared to R(-) chicken lines. The hypothalamic expression of
      the other studied genes remained unchanged between the two lines. In the fasted
      state, orexigenic neuropeptide Y and agouti-related peptide were more responsive,
      with higher significant levels in the R(+) compared to R(-) chickens, while no
      significant differences were seen for the anorexigenic neuropeptides pro
      opiomelanocortin and corticotropin releasing hormone. Interestingly, C-reactive
      protein, adiponectin receptor 1 and ghrelin receptor gene expression were
      significantly higher (12-, 2- and 3-folds, respectively), however ghrelin and
      melanocortin 5 receptor mRNA levels were lower (4- and 2-folds, P=0.05 and
      P=0.03, respectively) in R(+) compared to R(-) animals. We identified several key
      feeding-related genes that are differently expressed in the hypothalamus of R(+)
      and R(-) chickens and that might explain the difference in feed intake observed
      between the two lines.

PMID- 24857417
TI  - Diagnostic value of automated 3D ultrasound for incisional hernia.
AB  - The automated volume scanning system (AVSS) has been applied in breast diseases,
      but its use in incisional hernias has not been reported. In this study,
      conventional handheld B-mode ultrasound (HHUS) and AVSS examined a total of 122
      hernia defects in 78 patients. The results from two modalities were then compared
      with surgical findings for the purpose of assessing the diagnostic value of AVSS.
      Statistics showed that surgeries identified 38 small, 23 medium and 17 large
      incisional hernias. The results of AVSS completely agreed with surgical findings;
      however, HHUS misidentified nine large hernias as medium and seven medium hernias
      as large. AVSS proved to be more accurate than HHUS in measuring the length and
      width of the hernia. It also outperformed HHUS in both detecting the incisional
      hernias (91.8% vs. 78.7%, p = 0.00) and determining hernia contents (89.3% vs.
      68.0%, p = 0.00). Moreover, the coronal images AVSS obtained clearly displayed
      the shapes of the hernias, with 46 being regular and 32 irregular. Overall, AVSS
      can be used as a promising diagnostic modality for incisional hernias.

PMID- 24857416
TI  - Pulsed focused ultrasound treatment of muscle mitigates paralysis-induced bone
      loss in the adjacent bone: a study in a mouse model.
AB  - Bone loss can result from bed rest, space flight, spinal cord injury or age
      related hormonal changes. Current bone loss mitigation techniques include
      pharmaceutical interventions, exercise, pulsed ultrasound targeted to bone and
      whole body vibration. In this study, we attempted to mitigate paralysis-induced
      bone loss by applying focused ultrasound to the midbelly of a paralyzed muscle.
      We employed a mouse model of disuse that uses onabotulinumtoxinA-induced
      paralysis, which causes rapid bone loss in 5 d. A focused 2 MHz transducer
      applied pulsed exposures with pulse repetition frequency mimicking that of motor
      neuron firing during walking (80 Hz), standing (20 Hz), or the standard pulsed
      ultrasound frequency used in fracture healing (1 kHz). Exposures were applied
      daily to calf muscle for 4 consecutive d. Trabecular bone changes were
      characterized using micro-computed tomography. Our results indicated that
      application of certain focused pulsed ultrasound parameters was able to mitigate
      some of the paralysis-induced bone loss. 

PMID- 24857418
TI  - A cost-effective strategy for the bio-prospecting of mixed microalgae with high
      carbohydrate content: diversity fluctuations in different growth media.
AB  - In recent years, widespread efforts have been directed towards decreasing the
      costs associated with microalgae culture systems for the production of biofuels.
      In this study, a simple and inexpensive strategy to bio-prospect and cultivate
      mixed indigenous chlorophytes with a high carbohydrate content for biomethane and
      biohydrogen production was developed. Mixed microalgae were collected from four
      different water-bodies in Queretaro, Mexico, and were grown in Bold's basal
      mineral medium and secondary effluent from a wastewater treatment plant using
      inexpensive photo-bioreactors. The results showed large fluctuations in
      microalgal genera diversity based on different culture media and nitrogen
      sources. In secondary effluent, Golenkinia sp. and Scenedesmus sp. proliferated.
      The carbohydrate content, for secondary effluent, varied between 12% and 57%, and
      the highest volumetric and areal productivity were 61 mg L(-1)d(-1) and 4.6 g m(
      2)d(-1), respectively. These results indicate that mixed microalgae are a good
      feedstock for biomethane and biohydrogen production.

PMID- 24857419
TI  - A nitrido salt reagent of titanium.
AB  - Deprotonation of the parent titanium imido ((tBu)nacnac)Ti=NH(Ntolyl2)
      ((tBu)nacnac(-) = [ArNC(t)Bu]2CH; Ar = 2,6-(i)Pr2C6H3) with KCH2Ph forms a rare
      example of a molecular titanium nitride as a dimer,
      {[K][((tBu)nacnac)Ti=N(Ntolyl2)]}2. From the parent imido or nitride salt, the
      corresponding aluminylimido-etherate adduct,
      ((tBu)nacnac)Ti=N[AlMe2(OEt2)](Ntolyl2), can be isolated and structurally
      characterized. The parent imido is also a source for the related borylimido,
      ((tBu)nacnac)Ti?NBEt2(Ntolyl2). 

PMID- 24857420
TI  - Microbiota, gastrointestinal infections, low-grade inflammation, and antibiotic
      therapy in irritable bowel syndrome: an evidence-based review.
AB  - BACKGROUND: Post-infectious irritable bowel syndrome (PI-IBS) prevalence, small
      intestinal bacterial overgrowth (SIBO), altered microbiota, low-grade
      inflammation, and antibiotic therapy in IBS are all controversial issues. AIMS:
      To conduct an evidence-based review of these factors. METHODS: A review of the
      literature was carried out up to July 2012, with the inclusion of additional
      articles as far as August 2013, all of which were analyzed through the Oxford
      Centre for Evidence-Based Medicine (OCEBM) system. RESULTS: 1.There is greater
      SIBO probability in IBS when breath tests are performed, but prevalence varies
      widely (2-84%). 2.The gut microbiota in individuals with IBS is different from
      that in healthy subjects, but a common characteristic present in all the patients
      has not been established. 3.The incidence and prevalence of PI-IBS varies from 9
      10% and 3-17%, respectively, and the latter decreases over time. Bacterial
      etiology is the most frequent but post-viral and parasitic cases have been
      reported. 4.A sub-group of patients has increased enterochromaffin cells,
      intraepithelial lymphocytes, and mast cells in the intestinal mucosa, but no
      differences between PI-IBS and non-PI-IBS have been determined. 5.Methanogenic
      microbiota has been associated with IBS with constipation. 6.Rifaximin at doses
      of 400mg TID/10days or 550mg TID/14days is effective treatment for the majority
      of overall symptoms and abdominal bloating in IBS. Retreatment effectiveness
      appears to be similar to that of the first cycle. CONCLUSIONS: Further studies
      are required to determine the nature of the gut microbiota in IBS and the
      differences in low-grade inflammation between PI-IBS and non-PI-IBS. Rifaximin
      has shown itself to be effective treatment for IBS, regardless of prior factors.

PMID- 24857421
TI  - [Reversal of acute liver failure with N-acetylcysteine and prednisone in a
      patient with DRESS syndrome: a case report and literature review].

PMID- 24857422
TI  - Arthroscopic stabilization for recurrent shoulder instability with moderate
      glenoid bone defect in patients with moderate to low functional demand.
AB  - PURPOSE: The purpose of this study was to investigate the functional outcomes of
      arthroscopic Bankart repair for recurrent shoulder instability in the setting of
      moderate glenoid bone defect ranging from 20% to 30% in patients with moderate to
      low functional demand. METHODS: This study included 36 patients with unilateral
      recurrent instability and glenoid bone defects of 20% to 30% treated with
      arthroscopic stabilization. Glenoid bone loss was estimated on the en-face view
      of preoperative 3-dimensional computed tomography. Joint laxity was assessed
      clinically by use of the Beighton and Horan criteria, and patients were divided
      into 2 groups based on the presence of excessive joint laxity, group L (n = 13),
      or absence of excessive joint laxity, group N (n = 23). Functional assessments
      were performed with the patient-reported activity level; subjective shoulder
      value; Rowe score; and University of California, Los Angeles shoulder score.
      RESULTS: The mean glenoid defect size was 25.1% (range, 20% to 29%), and the
      overall functional outcomes improved significantly after surgery. A return to
      greater than 90% of the premorbid activity level was reported by 72% of patients
      (26 of 36 patients), and patient satisfaction was 83% (30 of 36 patients). There
      was no significant difference in functional outcomes between groups L and N
      (subjective shoulder value, 85.0% for group L v 88.9% for group N, P = .397; Rowe
      score, 83.5 for group L v 92.8 for group N, P = .537; and University of
      California, Los Angeles shoulder score, 32.2 for group L v 31.9 for group N, P =
      .697). Recurrent instability occurred in 4 patients (11%), 3 patients in group L
      (3 of 13, 23%) and 1 patient in group N (1 of 23, 4%), but this difference was
      not statistically significant (P = .125). CONCLUSIONS: Arthroscopic stabilization
      for recurrent shoulder instability in patients with moderate to low functional
      demand produced satisfactory outcomes despite the presence of moderate glenoid
      bone defects of 20% to 30%. For patients with excessive joint laxity, however,
      arthroscopic stabilization may not be reliable, with a recurrence rate of 23%.
      LEVEL OF EVIDENCE: Level IV, therapeutic case series.

PMID- 24857425
TI  - An important diagnosis for the hand surgeon: "the clenched fist syndrome".

PMID- 24857424
TI  - Signaling hypergraphs.
AB  - Signaling pathways function as the information-passing mechanisms of cells. A
      number of databases with extensive manual curation represent the current
      knowledge base for signaling pathways. These databases motivate the development
      of computational approaches for prediction and analysis. Such methods require an
      accurate and computable representation of signaling pathways. Pathways are often
      described as sets of proteins or as pairwise interactions between proteins.
      However, many signaling mechanisms cannot be described using these
      representations. In this opinion, we highlight a representation of signaling
      pathways that is underutilized: the hypergraph. We demonstrate the usefulness of
      hypergraphs in this context and discuss challenges and opportunities for the
      scientific community.

PMID- 24857426
TI  - [Cardiac tamponade following thrombolysis with low dose rt-PA].

PMID- 24857427
TI  - [Non-organic visual loss. A series of 5 cases].
AB  - Non-organic visual loss is the presence of ocular symptoms without an organic
      base that justifies it, and can occur in up to 5% of the children attending
      Ophthalmology Outpatients. A suspicion and the management of this situation are
      essential for a proper diagnosis, not only to avoid unnecessary referrals to
      other specialties, but also to avoid health spending, in addition to reducing
      parental distress by the possible presence of eye disease in their children. 

PMID- 24857423
TI  - SHIP1 regulates MSC numbers and their osteolineage commitment by limiting
      induction of the PI3K/Akt/beta-catenin/Id2 axis.
AB  - Here, we show that Src homology 2-domain-containing inositol 5'-phosphatase 1
      (SHIP1) is required for the efficient development of osteoblasts from mesenchymal
      stem cells (MSCs) such that bone growth and density are reduced in mice that lack
      SHIP1 expression in MSCs. We find that SHIP1 promotes the osteogenic output of
      MSCs by limiting activation of the PI3K/Akt/beta-catenin pathway required for
      induction of the MSC stemness factor Id2. In parallel, we demonstrate that mice
      with myeloid-restricted ablation of SHIP1, including osteoclasts (OCs), show no
      reduction in bone mass or density. Hence, diminished bone mass and density in the
      SHIP1-deficient mice results from SHIP deficiency in MSC and osteolineage
      progenitors. Intriguingly, mice with a SHIP-deficient MSC compartment also
      exhibit decreased OC numbers. In agreement with our genetic findings we also show
      that treatment of mice with an SHIP1 inhibitor (SHIPi) significantly reduces bone
      mass. These findings demonstrate a novel role for SHIP1 in MSC fate determination
      and bone growth. Further, SHIPi may represent a novel therapeutic approach to
      limit bone development in osteopetrotic and sclerotic bone diseases. 

PMID- 24857428
TI  - [Determining asthma treatment in children by monitoring fractional exhaled nitric
      oxide, sputum eosinophils and leukotriene B4].
AB  - Sputum eosinophils and exhaled fractional nitric oxide (FENO) are markers of
      airway inflammation in asthma. Cytokines, cysteinyl-leukotrienes and leukotriene
      B4 (LTB4) are responsible for this inflammation. The aim of this study is to
      determine the usefulness of these markers in monitoring asthma treatment in
      children. FENO, sputum eosinophils, and LTB4 in induced sputum were performed in
      10 children (9-15 years old). These determinations were repeated four months
      later, after the beginning or an increase in the treatment. FENO values tended to
      decrease (P=.15), pulmonary function tended to improve (P=.10), and sputum
      eosinophils decreased (P=.003) compared to the first determination. There were no
      differences in LTB4 concentrations (P=.88). Sputum eosinophils seem to be more
      precise than FENO in the monitoring of inflammation in asthmatic children. 

PMID- 24857429
TI  - [Buschke-Ollendorff syndrome].

PMID- 24857430
TI  - [Survival analysis of hematopoietic stem cell transplantation in children with
      primary immunodeficiency in Spain].
AB  - INTRODUCTION: Children with primary immunodeficiency have severe life-threatening
      infections and a higher prevalence of autoimmune problems, allergy and
      lymphoproliferative disorders. Allogenic hematopoietic stem cell transplantation
      has been the only potentially curative option. PATIENTS AND METHODS: Patients
      with primary immunodeficiency underwent allogenic stem cell transplantation in
      the period 1985-2011, and registered in the Spanish Working Party for Bone Marrow
      Transplantation in Children. RESULTS: One hundred and fifty nine patients
      underwent 173 allogenic stem cell transplantations, of whom 97 had severe
      combined immunodeficiency, 30 with immune dysregulation disorders, 25 Wiskott
      Aldrich syndrome, and 21 phagocyte disorders. The median patient age at diagnosis
      was 6 months (range: 17 days - 168 months) and the median patient age at
      transplant was 12 months (range: 1 month - 189 months). The donors were 30 (19%)
      identical siblings, 40 (25%) alternative family donors, and 89 (56%) unrelated
      donors. The source of stem cells was bone marrow in 68 (43%), cord blood in 52
      (33%), and peripheral blood in 39 (24%). Ninety eight (61.6%) are alive, 57
      (35.9%) died. Event-free survival at 10 years was 63%, with 90% for children
      transplanted from identical siblings, 36% for those transplanted from alternative
      family donors, and 66% for those transplanted from unrelated donors. CONCLUSIONS:
      The best results have been obtained with identical siblings, but other options
      may be considered.

PMID- 24857431
TI  - [Concurrent neonatal presentation of cystic fibrosis and maple syrup urine
      disease].

PMID- 24857432
TI  - [Pediamecum: one year of experience].
AB  - In 2011, the Spanish Association of Pediatrics decided to support the most
      ambitious project of its newly created Committee for Medicinal Products:
      Pediamecum. This is the first free on-line database with information on medicinal
      products for pediatric use in Spain. The web page http://pediamecum.es/ started
      on December 17 December 2012. One year later, Pediamecum includes 580 registered
      drugs. The website achieved more than one million page views by the end of 2013.
      Because of the first anniversary of Pediamecum, a survey was performed to request
      the feeling of users. Four hundred eighty-three responses were obtained. Ninety
      five percent believed that it is easy to navigate through the web, and 74% said
      that their doubts about the use of medicines in children were always resolved.
      The overall rating of Pediamecum is 7.5/10. The aims of Pediamecum are being
      accomplished; which is reflected essentially due to it becoming a useful tool for
      all professionals who care for children in their daily clinical practice. 

PMID- 24857433
TI  - Corneal biomechanics: a decade later.

PMID- 24857434
TI  - Paired versus unpaired significance testing: how improper statistical analysis
      altered interpretation of posterior surface changes after LASIK.

PMID- 24857435
TI  - Concepts and misconceptions in corneal biomechanics.
AB  - This review looks at biomechanical concepts and misconceptions related to in vivo
      assessment of corneal biomechanical response via air-puff deformation, including
      both human donor corneas and the translation of similar concepts to clinical
      studies. The impact of corneal viscoelasticity on interpreting clinical data is
      discussed, as well as the differences between 2 clinical devices that produce air
      puffs with distinct temporal and magnitude profiles. FINANCIAL DISCLOSURE: Dr.
      Roberts is a consultant to Oculus Optikgerate GmbH and Ziemer Ophthalmic Systems
      AG and has received research funding from Carl Zeiss Meditec AG as well as travel
      funds from Sooft Italia. She has no financial or proprietary interest in any
      material or method mentioned.

PMID- 24857436
TI  - In vivo characterization of corneal biomechanics.
AB  - Interest in corneal biomechanics has increased with the development of new
      refractive surgery techniques aimed at modifying corneal properties and a variety
      of surgical options for corneal ectasia management. The human cornea behaves as
      soft biological material. It is a viscoelastic tissue and its response to a force
      applied to it depends not only on the magnitude of the force, but also on the
      velocity of the application. There are concerns about the limitations to
      measuring corneal biomechanical properties in vivo. To date, 2 systems are
      available for clinical use: the Ocular Response Analyzer, a dynamic bidirectional
      applanation device, and the Corvis ST, a dynamic Scheimpflug analyzer device.
      These devices are useful in clinical practice, especially for planning some
      surgical procedures and earlier detection of ectatic conditions, but further
      research is needed to connect the clinical measurements obtained with these
      devices to the standard mechanical properties. FINANCIAL DISCLOSURE: Neither
      author has a financial or proprietary interest in any material or method
      mentioned.

PMID- 24857437
TI  - Deformation response of paired donor corneas to an air puff: intact whole globe
      versus mounted corneoscleral rim.
AB  - PURPOSE: To evaluate the influence of ocular shell biomechanical characteristics
      on corneal deformation response to an air puff. SETTING: The Ohio State
      University, Columbus, Ohio, USA. DESIGN: Experimental study. METHODS: Twenty-four
      eyes of 12 human donors were obtained in matched pairs. One eye was secured in a
      purpose-designed whole globe mount (whole-globe group). The cornea from the
      fellow eye was placed in a Barron artificial anterior chamber (artificial-chamber
      group). The corneas were mounted sequentially and connected to a pressure-control
      system. Deformation data were acquired using the Corvis ST, a dynamic Scheimpflug
      analyzer. Internal pressure was set to 10, 20, 30, 40, and 50 mm Hg; at least 4
      examinations were performed at each pressure. RESULTS: Statistically
      significantly higher maximum deformation amplitude was observed in the whole
      globe group than in the artificial-chamber group at all pressures. The mean
      amplitude differences were 1.006 mm +/- 0.238 [SD], 0.614 +/- 0.137 mm, 0.384 +/-
      0.099 mm, 0.229 +/- 0.087 mm, and 0.133 +/- 0.068 mm at 10, 20, 30, 40, and 50 mm
      Hg, respectively (P<.0001, P<.0001, P<.0001, P<.0001, and P<.0002, respectively).
      Nonlinear regression of the deformation amplitude differences between pairs
      showed a significant decrease with increasing pressure (P<.0001, R(2) = 0.8385).
      CONCLUSIONS: The deformation response to an air puff was affected by the type of
      mount used, with a stiffer shell producing a stiffer corneal response and
      decreasing differences at higher internal pressures. In vivo air-puff
      examinations may be affected by scleral stiffness in addition to the cornea.
      FINANCIAL DISCLOSURES: Dr. Roberts is a consultant to Oculus Optikgerate GmbH and
      Ziemer Ophthalmic Systems AG and has received research funding from Carl Zeiss
      Meditec AG and travel funds from Sooft Italia. No other author has a financial or
      proprietary interest in any material or method mentioned.

PMID- 24857438
TI  - Biomechanical and optical behavior of human corneas before and after
      photorefractive keratectomy.
AB  - PURPOSE: To evaluate numerically the biomechanical and optical behavior of human
      corneas and quantitatively estimate the changes in refractive power and stress
      caused by photorefractive keratectomy (PRK). SETTING: Athineum Refractive Center,
      Athens, Greece, and Politecnico di Milano, Milan, Italy. DESIGN: Retrospective
      comparative interventional cohort study. METHODS: Corneal topographies of 10
      human eyes were taken with a scanning-slit corneal topographer (Orbscan II)
      before and after PRK. Ten patient-specific finite element models were created to
      estimate the strain and stress fields in the cornea in preoperative and
      postoperative configurations. The biomechanical response in postoperative eyes
      was computed by directly modeling the postoperative geometry from the topographer
      and by reproducing the corneal ablation planned for the PRK with a numerical
      reprofiling procedure. RESULTS: Postoperative corneas were more compliant than
      preoperative corneas. In the optical zone, corneal thinning decreased the
      mechanical stiffness, causing local resteepening and making the central
      refractive power more sensitive to variations in intraocular pressure (IOP). At
      physiologic IOP, the postoperative corneas had a mean 7% forward increase in
      apical displacement and a mean 20% increase in the stress components at the
      center of the anterior surface over the preoperative condition. CONCLUSION:
      Patient-specific numerical models of the cornea can provide quantitative
      information on the changes in refractive power and in the stress field caused by
      refractive surgery. FINANCIAL DISCLOSURES: No author has a financial or
      proprietary interest in any material or method mentioned.

PMID- 24857439
TI  - Comparison of ocular biomechanical response parameters in myopic and hyperopic
      eyes using dynamic bidirectional applanation analysis.
AB  - PURPOSE: To compare differences in the ocular biomechanical response in myopic
      and hyperopic eyes. SETTING: London Vision Clinic, London, United Kingdom, The
      Ohio State University, Columbus, OH, United States. DESIGN: Retrospective study.
      METHODS: The study population included myopic and hyperopic patients evaluated
      preoperatively for refractive surgery at the London Vision Clinic between June
      2006 and May 2008. Biomechanical response parameters from the dynamic
      bidirectional applanation device (Ocular Response Analyzer) were analyzed using
      custom software for signal analysis, including corneal hysteresis (CH) and 10
      other output parameters. Hyperopic eyes were compared with myopic eyes first
      matched for age and pachymetry and then matched for age, pachymetry, and corneal
      compensated intraocular pressure (IOPcc). Nonpaired t tests were performed
      (P<.05) to compare parameters in the 2 groups. RESULTS: Consecutive patients
      included 2608 eyes with 1623 myopic eyes and 787 hyperopic eyes that met
      enrollment criteria. A significant correlation (P<.0001) was shown between CH and
      age (negative), pachymetry (positive), and IOPcc (negative). The first match
      included 473 eyes in each group, and the second match included 260 eyes in each
      group. When matching for age and pachymetry only, certain parameters implied that
      hyperopic eyes were stiffer, while others implied that myopic eyes were stiffer,
      but IOPcc was significantly greater in the myopic group. The second match, which
      also controlled for IOPcc, showed that all biomechanical parameters implied that
      hyperopic eyes were stiffer. CONCLUSIONS: Hyperopic eyes demonstrated stiffer
      response parameters than myopic eyes. Intraocular pressure was demonstrated to be
      a confounding factor when evaluating ocular biomechanical parameters. FINANCIAL
      DISCLOSURES: Proprietary or commercial disclosures are listed after the
      references.

PMID- 24857441
TI  - In vivo confocal laser microscopy of morphologic changes after simultaneous LASIK
      and accelerated collagen crosslinking for myopia: one-year results.
AB  - PURPOSE: To evaluate the safety of corneal collagen crosslinking (CXL) combined
      with laser in situ keratomileusis (LASIK). SETTING: Shinagawa LASIK Center,
      Tokyo, Japan. DESIGN: Case series. METHODS: Bilateral myopic LASIK patients had
      unilateral accelerated CXL (KXL System) in the nondominant eye. After LASIK,
      riboflavin 0.1% was instilled in the residual stromal bed for 60 seconds. After
      the riboflavin was washed out and the flap placed in its original position,
      ultraviolet-A light (30 mW/cm(2)) was administered for 60 seconds. The LASIK-CXL
      eyes and the LASIK-only eyes were compared. The uncorrected (UDVA) and corrected
      (CDVA) distance visual acuities, manifest refraction spherical equivalent (MRSE),
      keratometry values, endothelial cell density (ECD), pachymetry, optical coherence
      tomography (OCT), corneal hysteresis (CH), corneal resistance factor (CRF),
      keratoconus match index (KMI), and 37 parameters from a dynamic bidirectional
      applanation device (Ocular Response Analyzer) were analyzed. Morphologic changes
      were evaluated using confocal microscopy. RESULTS: No significant differences in
      UDVA, CDVA, MRSE, ECD, dynamic bidirectional applanation readings (eg, CH, CRF,
      KMI), or 37 additional parameters were found between the 2 groups (P>.05).
      Increased hyperreflectivity and a demarcation line similar to that seen after CXL
      were observed in the LASIK-CXL eyes. The demarcation line (mean depth 200.04 MUm
      +/- 27.01 [SD]; range 178 to 278 MUm) was present in 23 eyes (95.8%); the line
      was well defined in 2 eyes (8.3%) and faint in 21 eyes (87.5%). CONCLUSION:
      Combined LASIK-CXL was safe, causing insignificant corneal biomechanical and
      morphologic changes similar to those with CXL treatment only. FINANCIAL
      DISCLOSURE: No author has a financial or proprietary interest in any material or
      method mentioned.

PMID- 24857440
TI  - Comparison of biomechanical effects of small-incision lenticule extraction and
      laser in situ keratomileusis: finite-element analysis.
AB  - PURPOSE: To theoretically compare the corneal stress distribution of laser in
      situ keratomileusis (LASIK) with the stress distribution of small-incision
      lenticule extraction. SETTING: Cleveland Clinic Cole Institute, Cleveland, and
      The Ohio State University, Columbus, Ohio, USA. DESIGN: Computational modeling
      study. METHODS: A finite-element anisotropic collagen fiber-dependent model of
      myopic surgery using patient-specific corneal geometry was constructed for LASIK,
      small-incision lenticule extraction, and a geometry analog model with unaltered
      material properties from preoperative but with postoperative geometry including
      thickness. Surgical parameters, magnitude of myopic correction, LASIK flap
      thickness, and lenticule depth in small-incision lenticule extraction were
      varied. Two sets of models, 1 with uniform and 1 with depth-dependent material
      properties, were constructed. RESULTS: Stress distribution between small-incision
      lenticule extraction simulations and the geometry analog model were similar. In
      contrast, LASIK consistently reduced stress in the flap and increased stress in
      the residual stromal bed (RSB) compared with the geometry analog model. An
      increase in flap thickness or lenticule depth resulted in a greater increase in
      RSB stress in the LASIK model than in the small-incision lenticule extraction
      model. CONCLUSIONS: Small-incision lenticule extraction may present less
      biomechanical risk to the residual bed of susceptible corneas than comparable
      corrections involving LASIK flaps. Deeper corrections in the stroma may be
      possible in small-incision lenticule extraction without added risk for ectasia.
      FINANCIAL DISCLOSURES: Proprietary or commercial disclosures are listed after the
      references.

PMID- 24857442
TI  - Accelerated versus conventional corneal collagen crosslinking.
AB  - PURPOSE: To compare the outcomes of accelerated corneal collagen crosslinking
      (CXL) and conventional corneal CXL. SETTINGS: Private practice, Tokyo, Japan.
      DESIGN: Comparative study. METHODS: Eyes with keratoconus had accelerated CXL
      (KXL system; 15 minutes riboflavin [Vibex Rapid] presoak; 3 minutes 30 mW/cm(2)
      ultraviolet-A [UVA] light) or conventional CXL (CCL-365 Vario system; 30 minutes
      riboflavin [Vibex] presoak; 30 minutes 3 mW/cm(2) UVA light). The postoperative
      changes in visual acuity, keratometry readings, morphologic changes in the
      cornea, demarcation line existence, and corneal biomechanical responses with
      accelerated CXL and conventional CXL were compared. The follow-up was 1 year.
      RESULTS: The study enrolled 48 eyes of 39 patients; 30 eyes had accelerated CXL,
      and 18 eyes had conventional CXL. There were no statistically significant
      differences in postoperative changes in uncorrected or corrected distance visual
      acuity or in the manifest refraction spherical equivalent between the 2
      procedures. There were also no statistically significant differences in the
      postoperative changes in the keratometric readings from the Pentacam Scheimpflug
      device or the corneal biomechanical responses from a dynamic bidirectional
      applanation device (Ocular Response Analyzer) or a dynamic Scheimpflug analyzer
      (Corvis ST) between the procedures. Similar morphologic changes and a pronounced
      demarcation line were apparent in eyes in both groups postoperatively.
      CONCLUSIONS: Accelerated CXL and conventional CXL were both safe and effective.
      Accelerated CXL, being a fast procedure, appears to be more beneficial for
      patients and surgeons. FINANCIAL DISCLOSURE(S): No author has a financial or
      proprietary interest in any material or method mentioned.

PMID- 24857443
TI  - High-irradiance accelerated collagen crosslinking for the treatment of
      keratoconus: six-month results.
AB  - PURPOSE: To evaluate the effectiveness of accelerated corneal collagen
      crosslinking (CXL) with riboflavin for keratoconus by the change in dioptric
      power and corneal topography. SETTING: Private practice, Tokyo, Japan. DESIGN:
      Case series. METHODS: The accelerated CXL treatments (KXL system) were performed
      using a 10-minute riboflavin 0.1% (Vibex Rapid) soak and a 3-minute ultraviolet-A
      (UVA) irradiance at a level of 30 mW/cm(2). This corresponds to a total radiant
      exposure of 5.4 J/cm(2). Preoperative and 1, 3, and 6 months postoperative
      examinations were performed. RESULTS: The study enrolled 39 eyes of 22 patients.
      The mean uncorrected distance visual acuity showed a statistically significant
      improvement, from 1.11 +/- 0.42 logMAR preoperatively to 0.89 +/- 0.53 logMAR 6
      months postoperatively (P<.01). The mean maximum keratometry readings also
      changed significantly, from 49.95 +/- 6.11 diopters (D) preoperatively to 49.19
      +/- 5.82 D at 6 months (P<.01). There were no statistically significant changes
      in the endothelial cell density between preoperatively and postoperatively.
      CONCLUSIONS: The changes after accelerated CXL were similar to those after
      conventional CXL. Thus, accelerated CXL has the potential to efficiently treat
      and halt the progression of keratoconus and may be an effective, efficient
      therapeutic option for treating corneal ectatic disease. FINANCIAL DISCLOSURES:
      No author has a financial or proprietary interest in any material or method
      mentioned.

PMID- 24857444
TI  - Refractive surgical problem: June consultation #1.

PMID- 24857445
TI  - June consultation #2.

PMID- 24857446
TI  - June consultation #3.

PMID- 24857447
TI  - June consultation #4.

PMID- 24857448
TI  - June consultation #5.

PMID- 24857449
TI  - June consultation #6.

PMID- 24857450
TI  - June consultation #8.

PMID- 24857451
TI  - June consultation #7.

PMID- 24857452
TI  - Reply: Intraocular pressure spike prophylaxis in glaucoma patients 1 day after
      phacoemulsification.

PMID- 24857453
TI  - Intraocular pressure spike prophylaxis in glaucoma patients 1 day after
      phacoemulsification.

PMID- 24857454
TI  - Minimizing inflammation after congenital cataract surgery.

PMID- 24857455
TI  - Practicing the preach.

PMID- 24857456
TI  - Reply: To PMID 24530023.

PMID- 24857457
TI  - Manual tunnel incision cataract surgery with sandwich technique in eyes with
      microcornea.

PMID- 24857458
TI  - BMP2-encapsulated chitosan coatings on functionalized Ti surfaces and their
      performance in vitro and in vivo.
AB  - Bone morphogenic protein-2 (BMP2)-encapsulated chitosan (CS) coatings were
      prepared to immobilize BMP2 on titanium (Ti) surfaces. The Ti substrates were
      functionalized through a three-step process: alkali treatment, silanization with
      3-aminopropyltriethoxysilane and aldehydation with glutaraldehyde (GA). BMP2
      encapsulated CS coatings (BMP2-CS) were bonded to Ti surfaces through reactions
      between the aldehyde groups of GA and the amine groups of CS. Direct BMP2
      immobilization on aldehyde-treated Ti (BMP2-Ti) and pure CS coatings (CS-Ti) were
      used as controls. The release rate of BMP2-CS-Ti was half of that of BMP2-Ti at
      initial stage, which indicates that the CS coatings are suitable carriers for
      sustained BMP2 release. The osteoinductivities of BMP2-CS-Ti, BMP2-Ti, CS-Ti and
      pristine Ti were examined by both in vitro cell tests and in vivo experiments.
      Bone marrow stem cell (BMSC) culture indicated that BMP2-CS-Ti is more potent in
      stimulating the differentiation of the adhering BMSC than the three other groups.
      Rabbit femur implantation revealed the excellent osteoinductivity of BMP2-CS
      coated Ti implants. These results demonstrate that the BMP2-encapsulated CS
      coatings are stable osteoinductive coatings that realize the sustained release of
      BMP2 and maintain the activity of the protein.

PMID- 24857459
TI  - Preparation and application of a novel electrochemical sensing material based on
      surface chemistry of polyhydroquinone.
AB  - A new analogue of polydopamine (PDA), i.e., polyhydroquinone (PH2Q), was
      polymerized and its surface chemistry was studied by different ways of
      characterization. PH2Q was produced by the self-polymerization of H2Q mediated by
      dissolved oxygen, and the self-polymerization process was strongly dependent on
      the type and the pH value of the buffer solutions. PH2Q can not only achieve
      surface hydrophilization of different substrates like polyethylene terephthalate
      (PET) film, graphite strip, C12SH/Au and wax slice, but also possess several
      unique properties like reversible adsorption, good solubility and low cost. These
      properties made PH2Q an ideal polymeric modifier for the noncovalent
      functionalization of some nanomaterials. By simply grinding with PH2Q, pristine
      multi-walled carbon nanotubes (MWNTs) can be readily dispersed in water with high
      solubility and good stability. The resulting MWNT-PH2Q composite exhibited
      excellent electrochemical performance, which was employed for the simultaneous
      determination of dopamine (DA) and uric acid (UA).

PMID- 24857460
TI  - Spark plasma sintered Al2O3-YSZ-TiO2 composites: processing, characterization and
      in vivo evaluation.
AB  - Al2O3 and Al2O3-YSZ composites containing 3 and 5 wt.% TiO2 were prepared by
      spark plasma sintering at temperatures of 1350-1400 degrees C for 300s under a
      pressure of 40 MPa. The grain growth of alumina was suppressed by the addition of
      YSZ. Al2O3-YSZ composites showed higher hardness than monolithic Al2O3. There was
      not a considerable difference in hardness values for Al2O3-YSZ composites
      containing 10 and 20 vol.% YSZ and the addition of TiO2 decreased the hardness of
      the composites. The fracture toughness of Al2O3 increased from 2.8 MPa.m(1/2) to
      4.3 MPa.m(1/2) with the addition of 10vol.% YSZ, further addition resulted in
      higher fracture toughness values. The fracture toughness values were increased
      with TiO2 addition and the highest value of fracture toughness, 5.3 MPa.m(1/2),
      was achieved with the addition of 20 vol.% YSZ and 5 wt.% TiO2. Preliminary in
      vivo tests demonstrated the biocompatibility and osseointegration of the
      composites after 6 week post-implantation in femur of Wistar rats.

PMID- 24857461
TI  - Release of silver and copper nanoparticles from polyethylene nanocomposites and
      their penetration into Listeria monocytogenes.
AB  - Since infection is a major cause of death in a patient whose immune responses
      have been compromised (immunocompromised patient), considerable attention has
      been focused on developing materials for the prevention of infections. This has
      been directed primarily at suppressing or eliminating the host's endogenous
      microbial burden and decreasing the acquisition of new organisms. In this study,
      the antibacterial properties of two nanocomposites, polyethylene modified with
      silver nanoparticles (PE-AgNps) or copper nanoparticles (PE-CuNps), against
      Listeria monocytogenes have been investigated. In order to elucidate the
      antibacterial mechanism, specifically whether this mechanism corresponds to
      bactericidal or bacteriolytic activities, we have determined the extent of
      release of metal ions (Ag(+) and Cu(2+)) and, also, the morphology of the
      bacteria. The metal ion release from nanocomposites was followed by inductively
      coupled plasma spectrometry and the morphology of the bacteria was revealed
      through examination of ultramicrotomed sections of bacteria in a transmission
      electron microscope. The study of metal ion release from the nanocomposites shows
      that for both nanocomposites the amount of ions released varies with time, which
      initially displays a linear behavior until an asymptotic behavior is reached.
      Further, TEM images show that silver nanoparticles (AgNps) and copper
      nanoparticles (CuNps), which are released from the nanocomposites, can penetrate
      to the cell wall and the plasma membrane of bacteria. Resulting morphological
      changes involve separation of the cytoplasmic membrane from the cell wall, which
      is known to be an effect of plasmolysis. It was revealed that the antibacterial
      abilities of the two nanocomposites against L. monocytogenes are associated with
      both bactericidal and bacteriolytic effects.

PMID- 24857462
TI  - Ferroelectric polymer scaffolds based on a copolymer of tetrafluoroethylene with
      vinylidene fluoride: fabrication and properties.
AB  - A solution blow spinning technique is a method developed recently for making
      nonwoven webs of micro- and nanofibres. The principal advantage of this method
      compared to a more traditional electrospinning process is its significantly
      higher production rate. In this work, the solution blow spinning method was
      further developed to produce nonwoven polymeric scaffolds based on a copolymer of
      tetrafluoroethylene with vinylidene fluoride solution in acetone. A crucial
      feature of the proposed method is that high-voltage equipment is not required,
      which further improves the method's economics. Scanning electron microscopy
      analysis of the samples demonstrated that the surface morphology of the nonwoven
      materials is dependent on the polymer concentration in the spinning solution. It
      was concluded that an optimum morphology of the nonwoven scaffolds for medical
      applications is achieved by using a 5% solution of the copolymer. It was
      established that the scaffolds produced from the 5% solution have a fractal
      structure and anisotropic mechanical properties. X-ray diffraction, infrared
      spectroscopy, Raman spectroscopy and differential scanning calorimetry
      demonstrated that the fabricated nonwoven materials have crystal structures that
      exhibit ferroelectric properties. Gas chromatography has shown that the amount of
      acetone in the nonwoven material does not exceed the maximum allowable
      concentration of 0.5%. In vitro analysis, using the culture of motile cells,
      confirmed that the nonwoven material is non-toxic and does not alter the morpho
      functional status of stem cells for short-term cultivation, and therefore can
      potentially be used in medical applications. 

PMID- 24857463
TI  - Preparation of mesoporous silica thin films by photocalcination method and their
      adsorption abilities for various proteins.
AB  - Mesoporous silica (MPS) thin film biosensor platforms were established. MPS thin
      films were prepared from tetraethoxysilane (TEOS) via using sol-gel and spin
      coating methods using a poly-(ethylene oxide)-block-poly-(propylene oxide)-block
      poly-(ethylene oxide) triblock polymer, such as P123 ((EO)20(PO)70(EO)20) or F127
      ((EO)106(PO)70(EO)106), as the structure-directing agent. The MPS thin film
      prepared using P123 as the mesoporous template and treated via vacuum ultraviolet
      (VUV) irradiation to remove the triblock copolymer had a more uniform pore array
      than that of the corresponding film prepared via thermal treatment. Protein
      adsorption and enzyme-linked immunosorbent assay (ELISA) on the synthesized MPS
      thin films were also investigated. VUV-irradiated MPS thin films adsorbed a
      smaller quantity of protein A than the thermally treated films; however, the
      human immunoglobulin G (IgG) binding efficiency was higher on the former. In
      addition, protein A-IgG specific binding on MPS thin films was achieved without
      using a blocking reagent; i.e., nonspecific adsorption was inhibited by the
      uniform pore arrays of the films. Furthermore, VUV-irradiated MPS thin films
      exhibited high sensitivity for ELISA testing, and cytochrome c adsorbed on the
      MPS thin films exhibited high catalytic activity and recyclability. These results
      suggest that MPS thin films are attractive platforms for the development of novel
      biosensors. 

PMID- 24857464
TI  - Determination of serotonin on platinum electrode modified with carbon
      nanotubes/polypyrrole/silver nanoparticles nanohybrid.
AB  - A new sensor has been developed by a simple electrodeposition of multi-walled
      carbon nanotubes (MWCNT), polypyrrole (PPy) and colloidal silver nanoparticles on
      the platinum (Pt) electrode surface. The Pt/MWCNT/PPy/AgNPs electrode was applied
      to the detection of serotonin in plasmatic serum samples using differential pulse
      voltammetry (DPV). The synergistic effect of MWCNT/PPy/AgNPs nanohybrid formed
      yielded a LOD of 0.15 MUmol L(-1) (26.4 MUg L(-1)). Reproducibility and
      repeatability values of 2.2% and 1.7%, respectively, were obtained compared to
      the conventional procedure. The proposed electrode can be an effective material
      to be used in biological analysis.

PMID- 24857465
TI  - Electrophoretic co-deposition of polyvinyl alcohol (PVA) reinforced alginate
      Bioglass(r) composite coating on stainless steel: mechanical properties and in
      vitro bioactivity assessment.
AB  - PVA reinforced alginate-bioactive glass (BG) composite coatings were produced on
      stainless steel by a single step electrophoretic deposition (EPD) process. The
      present paper discusses the co-deposition mechanism of the three components and
      presents a summary of the relevant properties of the composite coatings deposited
      from suspensions with different PVA concentrations. Homogeneous composite
      coatings with compact microstructure and increased thickness, i.e. as high as 10
      MUm, were observed by scanning electron microscopy (SEM). The surface roughness
      of coatings with different PVA contents was slightly increased, while a
      significant increase of water contact angles due to PVA addition was detected and
      discussed. Improved adhesion strength of coatings containing different amounts of
      PVA was quantitatively and qualitatively confirmed by pull-off adhesion and
      cycled bending tests, respectively. In-vitro bioactivity tests were performed in
      simulated body fluid (SBF) for 0.5, 1, 2, 4, 7, and 14 days, respectively. The
      decomposition rate of the coatings was reduced with PVA content, and rapid
      hydroxyapatite forming ability of the composite coatings in SBF was confirmed by
      FTIR and XRD analyses. According to the results of this study, composite alginate
      Bioglass(r) bioactive coatings combined with PVA are proposed as promising
      candidates for dental and orthopedic applications.

PMID- 24857466
TI  - Dialysis as a method of obtaining neutral collagen gels.
AB  - Collagen gels are useful materials for medicine and tissue engineering. They are
      generally obtained by chemical cross-linking of the protein chains. However,
      other kinds of interactions can also stabilize the structure. In our
      investigations we employed dialysis against deionised water as a method of
      neutralization of collagen solution. This promoted the creation of stable,
      flexible, transparent gel composed only of collagen and water. The FTIR-ATR
      spectroscopy showed that changing pH of the solution caused organization of
      collagen chains into triple-helical motifs similar to native protein. As a
      result, thermal stability of the material improved and the surface was more polar
      than in case of collagen film obtained from acidic solution. The freeze-drying of
      the gel provided the relatively stiff, porous material, which returned to its
      original shape after deformation. We expect that the method of obtaining neutral
      collagen gels can be widely applied for preparation of scaffolds for tissue
      engineering. 

PMID- 24857467
TI  - Fabrication, characterization and in vitro biocompatibility evaluation of porous
      Ta-Nb alloy for bone tissue engineering.
AB  - Porous Ta-Nb alloys were fabricated using the sponge impregnation technique and
      the powder metallurgy technique (P/M) in combination. All porous Ta-Nb alloys
      displayed interconnected open cell structures with porosities around 64% and pore
      sizes in the range of 300-500 MUm. No carbide, oxide, or intermetallic-related
      phases were detected by the X-ray diffraction (XRD). Porous Ta-Nb alloys
      displayed sintering neck growth, smoother surface of the particles and more
      shrinkage of the micropores, with Nb contents increasing from 5% to 15%. The
      compressive strength and Young's modulus of the Ta-Nb alloys agreed well with the
      requirements of trabecular bone. The normalized compressive plateau stress and
      Young's modulus increased from 52.27 MPa to 85.43 MPa and from 1.850 GPa to 2.540
      GPa, respectively, with Nb contents increasing from 5% to 15%. Porous Ta-Nb
      alloys had no cytotoxicity and possessed the excellent biocompatibility similar
      to porous Ta scaffolds.

PMID- 24857468
TI  - Novel injectable biomaterials for bone augmentation based on isosorbide
      dimethacrylic monomers.
AB  - Drawbacks with the commonly used PMMA-based bone cements, such as an excessive
      elastic modulus and potentially toxic residual monomer content, motivate the
      development of alternative cements. In this work an attempt to prepare an
      injectable biomaterial based on isosorbide-alicyclic diol derived from renewable
      resources was presented. Two novel dimethacrylic monomers ISDGMA - 2,5-bis(2
      hydroxy-3-methacryloyloxypropoxy)-1,4:3,6-dianhydro-sorbitol and ISETDMA -
      dimethacrylate of ethoxylated isosorbide were synthesized and used to prepare a
      series of low-viscosity compositions comprising bioactive nano-sized
      hydroxyapatite in the form of a two-paste system. Formulations exhibited a non
      Newtonian shear-thinning behavior, setting times between 2.6 min and 5.3 min at
      37 degrees C and maximum curing temperatures of 65 degrees C. Due to the
      hydrophilic nature of ISDGMA, cured compositions could absorb up to 13.6% water
      and as a result the Young's modulus decreased from 1,429 MPa down to 470 MPa.
      Both, poly(ISDGMA) and poly(ISETDMA) were subjected to a MTT study on mice
      fibroblasts (BALB/3T3) and gave relative cell viabilities above 70% of control. A
      selected model bone cement was additionally investigated using human osteosarcoma
      cells (SaOS-2) in an MTS test, which exhibited concentration-dependent cell
      viability. The preliminary results, presented in this work reveal the potential
      of two novel dimethacrylic monomers in the preparation of an injectable
      biomaterial for bone augmentation, which could overcome some of the drawbacks
      typical for conventional acrylic bone cement.

PMID- 24857469
TI  - Silk fibroin and sodium alginate blend: miscibility and physical characteristics.
AB  - Films of silk fibroin (SF) and sodium alginate (SA) blends were prepared by
      solution casting technique. The miscibility of SF and SA in those blends was
      evaluated and scanning electron microscopy (SEM) revealed that SF/SA 25/75 wt.%
      blends underwent microscopic phase separation, resulting in globular structures
      composed mainly of SF. X-ray diffraction indicated the amorphous nature of these
      blends, even after a treatment with ethanol that turned them insoluble in water.
      Thermal analyses of blends showed the peaks of degradation of pristine SF and SA
      shifted to intermediate temperatures. Water vapor permeability, swelling capacity
      and tensile strength of SF films could be enhanced by blending with SA. Cell
      viability remained between 90 and 100%, as indicated by in vitro cytotoxicity
      test. The SF/SA blend with self-assembled SF globules can be used to modulate
      structural and mechanical properties of the final material and may be used in
      designing high performance wound dressing.

PMID- 24857470
TI  - Sintering and mechanical properties of the alumina-tricalcium phosphate-titania
      composites.
AB  - The objective of this study was to determine the effect of the content of titania
      and the sintering process on the transformation phase, the densification, the
      rupture strength and the microstructures of the alumina-10 wt.% tricalcium
      phosphate composites. After the sintering process, the samples were examined by
      using (31)P and (27)Al magic angle scanning nuclear magnetic resonance, X-ray
      powder diffraction and scanning electron microscopy analysis. The Brazilian test
      was used to measure the rupture strength of the samples. The present results
      provide new information about solid-state reactivity in the ternary system alpha
      alumina-beta-tricalcium phosphate-anatase-titania. The differential thermal
      analysis of the alpha-alumina-beta-tricalcium phosphate-titania composites shows
      two endothermic peaks, at 1360  degrees C and at 1405  degrees C, which are
      caused by the reactions between titania/alumina and titania/tricalcium phosphate,
      respectively. Thus, the presence of titania in the alumina-10 wt.% tricalcium
      phosphate leads to the formation of beta-Al2TiO5 at 1360  degrees C. At 1600 
      degrees C, the alumina-10 wt.% tricalcium phosphate-5 wt.% titania composites
      displayed the highest rupture strength (74 MPa), compared to the alumina-10 wt.%
      tricalcium phosphate composites (13.5 MPa). Accordingly, the increase of the
      rupture strength is due to the formation of the new beta-Al2TiO5 phase.

PMID- 24857471
TI  - Synthesis of magnetic FexOy@silica-pillared clay (SPC) composites via a novel sol
      gel route for controlled drug release and targeting.
AB  - Novel magnetic silica-pillared clay (SPC) materials with an ordered interlayered
      mesopore structure were synthesized via a two-step method including gallery
      molecular self-assembly and sol-gel magnetic functionalization, resulting in the
      formation of FexOy@SPC composites. Small-angle XRD, TEM and N2 adsorption
      desorption isotherms results show that these composites conserved a regular
      layered and ordered mesoporous structure after the formation of FexOy
      nanoparticles. Wide-angle XRD and XPS analyses confirmed that the FexOy generated
      in these mesoporous silica-pillared clay hosts is mainly composed of gamma-Fe2O3.
      Magnetic measurements reveal that these composites with different gamma-Fe2O3
      loading amounts possess super-paramagnetic properties at 300K, and the saturation
      magnetization increases with increasing Fe ratio loaded. Compared to the pure
      SPC, the in vitro drug release rate of the FexOy@SPC composites was enhanced due
      to the fact that the intensities of the SiOH bands on the pore surface of SPC
      decrease after the generation of FexOy. However, under an external magnetic field
      of 0.15T, the drug release rate of the FexOy@SPC composites decreases
      dramatically owing to the aggregation of the magnetic FexOy@SPC particles
      triggered by non-contact magnetic force. The obtained FexOy@SPC composites imply
      the possibility of application in magnetic drug targeting. 

PMID- 24857472
TI  - Computer-assisted electrochemical fabrication of a highly selective and sensitive
      amperometric nitrite sensor based on surface decoration of electrochemically
      reduced graphene oxide nanosheets with CoNi bimetallic alloy nanoparticles.
AB  - For the first time, a novel, robust and very attractive statistical experimental
      design (ED) using minimum-run equireplicated resolution IV factorial design (Min
      Run Res IV FD) coupled with face centered central composite design (FCCCD) and
      Derringer's desirability function (DF) was developed to fabricate a highly
      selective and sensitive amperometric nitrite sensor based on electrodeposition of
      CoNi bimetallic alloy nanoparticles (NPs) on electrochemically reduced graphene
      oxide (ERGO) nanosheets. The modifications were characterized by cyclic
      voltammetry (CV), electrochemical impedance spectroscopy (EIS), energy dispersive
      X-ray spectroscopic (EDS), scanning electron microscopy (SEM) techniques. The
      CoNi bimetallic alloy NPs were characterized using digital image processing (DIP)
      for particle counting (density estimation) and average diameter measurement.
      Under the identified optimal conditions, the novel sensor detects nitrite in
      concentration ranges of 0.1-30.0 MUM and 30.0-330.0 MUM with a limit of detection
      (LOD) of 0.05 MUM. This sensor selectively detects nitrite even in the presence
      of high concentration of common ions and biological interferents therefore, we
      found that the sensor is highly selective. The sensor also demonstrated an
      excellent operational stability and good antifouling properties. The proposed
      sensor was used to the determination of nitrite in several foodstuff and water
      samples.

PMID- 24857473
TI  - Importance of nucleation in transformation of octacalcium phosphate to
      hydroxyapatite.
AB  - Octacalcium phosphate (OCP) is regarded as an in vivo precursor of hydroxyapatite
      (HA). It is important to understand the mechanism of transformation of OCP to HA
      in order to reveal the mechanism of mineralization and help in the development of
      artificial bone-repairing materials. Herein, we have examined the behavior of OCP
      in a simulated body fluid (SBF) and pure water. The OCP particles immersed in the
      SBF at 37  degrees C did not transform to HA even after 720 h of immersion,
      though the particles showed crystal growth. In distilled water at 60  degrees C,
      the OCP particles transformed to HA but the unreactive period was observed.
      Although the immersed solution became supersaturated with HA within 12h of
      immersion, the OCP was not transformed in the first 36 h of immersion. These
      results indicate that the nucleation of HA is the rate-determining step in the
      transformation of OCP to HA.

PMID- 24857474
TI  - Effects of carbon concentration on microstructure and mechanical properties of as
      cast nickel-free Co-28Cr-9W-based dental alloys.
AB  - We determined the effects of carbon concentration on the microstructures and
      tensile properties of the Ni-free Co-29Cr-9W-1Si-C (mass%) cast alloys used in
      dental applications. Alloy specimens prepared with carbon concentrations in the
      range 0.01-0.27 mass% were conventionally cast. Scanning electron microscopy
      (SEM) and electron probe microanalysis (EPMA) revealed that precipitates had
      formed in all the alloy specimens. The sigma phase, a chromium-rich intermetallic
      compound, had formed in the region between the dendrite arms of the low-carbon
      content (e.g., 0.01 C) alloys. Adding carbon to the alloys increased the amount
      of interdendritic precipitates that formed and changed the precipitation
      behavior; the precipitated phase changed from the sigma phase to the M23C6
      carbide with increasing carbon concentration. Adding a small amount of carbon
      (i.e., 0.04 mass%) to the alloys dramatically enhanced the 0.2% proof stress,
      which subsequently gradually increased with increasing content of carbon in the
      alloys. Elongation-to-failure, on the other hand, increased with increasing
      carbon content and showed a maximum at carbon concentrations of ~0.1 mass%. The
      M23C6 carbide formed at the interdendritic region may govern the tensile
      properties of the as-cast Co-Cr-W alloys similar to how it governed those of the
      hot-rolled alloys prepared in our previous study.

PMID- 24857475
TI  - Preparation and characterisation of thermoresponsive nanogels for smart
      antibacterial fabrics.
AB  - The present investigation involves the preparation and characterisation of silver
      containing nanogels and their incorporation onto the surface of woven fabrics so
      that they can be potentially used in biomedical applications such as wound
      dressings. These silver nanoparticles were mixed with N-isopropylacrylamide
      (NIPAM) based nanogels during and at the end of polymerisation process prior to
      their application onto the fabrics. NIPAM based nanogels were found to have a
      peak of lower critical solution temperature (LCST) that is close to the human
      body temperature. These nanogels were applied on cotton fabrics and cured for 15
      h at 30 degrees C. Silver based nanogels were padded onto the fabrics followed by
      drying at 30 degrees C overnight. Scanning electron microscopy images have shown
      excellent distribution of silver nanoparticles on the fabric surface. EDX
      analysis was also conducted to confirm the presence of silver particles on the
      fabric surface. The results showed that a cotton fabric treated with silver based
      nanogels prevented the growth of bacteria, i.e. Gram-positive (Staphylococcus
      epidermidis) and Gram-negative (Escherichia coli), on whereas the control cotton
      fabric samples exhibited considerable level of bacterial growth. Specifically,
      the nanogels in which the silver particles were added during the polymerisation
      process were observed to have higher antibacterial efficacy towards both types of
      bacteria.

PMID- 24857476
TI  - Evaluation of the biocompatibility of NiTi dental wires: a comparison of
      laboratory experiments and clinical conditions.
AB  - Effects of intraoral environment on the surface degradation of nickel-titanium
      (NiTi) shape memory alloy orthodontic wires was simulated through ex situ static
      immersion experiments in artificial saliva. The tested wires were compared to
      companion wires retrieved from patients in terms of chemical changes and
      formation of new structures on the surface. Results of the ex situ experiments
      revealed that the acidic erosion effective at the earlier stages of immersion led
      to the formation of new structures as the immersion period approached 30 days.
      Moreover, comparison of these results with the analysis of wires utilized in
      clinical treatment evidenced that ex situ experiments are reliable in terms
      predicting C-rich structure formation on the wire surfaces. However, the
      formation of C pileups at the contact sites of arch wires and brackets could not
      be simulated with the aid of static immersion experiments, warranting the
      simulation of the intraoral environment in terms of both chemical and physical
      conditions, including mechanical loading, when evaluating the biocompatibility of
      NiTi orthodontic arch wires.

PMID- 24857477
TI  - A novel functional conducting polymer as an immobilization platform.
AB  - Here, we present the fabrication of conducting polymer based enzymatic and
      microbial biosensors. To obtain immobilization platforms for both pyranose
      oxidase (PyOx) and Gluconobacter oxydans, the graphite electrode surface was
      modified with the polymer of 4-amino-N-(2,5-di(thiophen-2-yl)-1H-pyrrol-1
      yl)benzamide (HKCN) which has free amino groups on the surface for further
      bioconjugation reactions with the biomolecules. Initially, the electrode surface
      was covered with HKCN via electropolymerization. Then, either PyOx or G. oxydans
      cell was stabilized using glutaraldehyde as a cross-linker. After optimization of
      biosensors, analytical characterization and surface imaging studies were
      investigated. The change of current depends on glucose concentration between 0.05
      1.0mM and 0.25-2.5mM with HKCN/PyOx and HKCN/G. oxydans biosensors in batch
      systems. Also, the calibration graphs were obtained for glucose in FIA mode, and
      in this case, linear ranges were found to be 0.01-1.0mM and 0.1-7.5mM for
      HKCN/PyOx and HKCN/G. oxydans, respectively. 

PMID- 24857478
TI  - Towards optimization of the silanization process of hydroxyapatite for its use in
      bone cement formulations.
AB  - The aim of this work was to provide some fundamental information for optimization
      of silanization of hydroxyapatite intended for bone cement formulations. The
      effect of 3-(trimethoxysilyl) propyl methacrylate (MPS) concentration and solvent
      system (acetone/water or methanol/water mixtures) during HA silanization was
      monitored by X-ray diffraction (XRD), FTIR spectroscopy and EDX analysis. The
      effect of silanized HA on the mechanical properties of acrylic bone cements is
      also reported. It was found that the silanization process rendered hydroxyapatite
      with lower crystallinity compared to untreated HA. Through EDX, it was observed
      that the silicon concentration in the HA particles was higher for acetone-water
      than that obtained for methanol-water system, although the mechanical performance
      of cements prepared with these particles exhibited the opposite behavior. Taking
      all these results together, it is concluded that methanol-water system containing
      MPS at 3wt.% provides the better results during silanization process of HA.

PMID- 24857479
TI  - Comparative study of adsorption capacity of mesoporous silica materials for
      molsidomine: effects of functionalizing and solution pH.
AB  - Adsorption capacities of mesoporous silica materials having various surface
      functional groups (hydroxyl, phenyl, mercaptopropyl, aminopropyl) at pH values of
      4.8, 7.4, and 8.0 were studied. It was found that the maximum amount of adsorbed
      molsidomine is affected by method of preparation of the silica materials,
      chemistry of their surfaces and solution pH from where adsorption is carried out.
      The effects were explained by different states of the adsorbents and molsidomine
      in solution at the studied pH. The most efficient adsorption of molsidomine is
      observed onto phenyl modified silica prepared by grafting at pH4.8. Aminopropyl
      modified silica adsorbs the lowest amount of molsidomine and the adsorption was
      observed only at pH7.4. Interactions responsible for the adsorption were
      elucidated by spectroscopic studies.

PMID- 24857480
TI  - A study on the influence of Ni-Ti M-Wire in the flexural fatigue life of
      endodontic rotary files by using Finite Element Analysis.
AB  - The aim of this paper is to analyze the cyclic performance of two different Ni-Ti
      endodontic rotary files made from different alloys under bending using Finite
      Element Analysis (FEA). When experimentation is not available, this is not a
      trivial task and most papers on the subject rely on static analysis only. Two Ni
      Ti rotary instruments are selected, ProFile GT and a GT Series X (GTX). The
      latter file is made from M-Wire, which has been thermo-mechanically processed to
      have larger flexibility, according to its manufacturer. The mechanical response
      was studied by considering different scenarios in the FEA package, in which the
      material properties were introduced according to existing literature. The method
      and results are presented and discussed so that this paper can be used as a
      guideline for future works. Although not fully reflective of the instrument's
      behavior in a dynamic rotation intra-canal system, the models used constitute a
      good approximation when a comparison between two instruments is at stake. It is
      shown that the GTX file has a lower risk of fatigue fracture during its clinical
      use when compared to the GT file, especially when the root canal makes the file
      deform into an extreme geometry. However, if the root canal does not make the
      file deform more than a certain amount, the GT file is equally good from the
      point of view of mechanical endurance.

PMID- 24857482
TI  - The responses of endothelial cells to Zr6 1Ti 2Cu25Al12 metallic glass in vitro
      and in vivo.
AB  - The goal of this study was to evaluate the biocompatibility of newly developed
      Zr61Ti2Cu25Al12 metallic glass (denoted ZT1) and its parallel material,
      commercially pure titanium (CP-Ti), as dental implants. To this end, we evaluated
      their cytotoxicity in vitro using human umbilical vein endothelial cells (HUVECs)
      and in vivo by performing an oral mucosa irritation test in hamsters.
      Specifically, cytotoxicity was determined in HUVECs by evaluating their cell
      morphology using scanning electron microscopy (SEM) and their cell viability
      using CCK-8 assays. Moreover, we examined the mRNA levels of vascular endothelial
      growth factor and von Willebrand factor by quantitative PCR (qPCR). In the early
      stages of proliferation and differentiation, no differences were observed between
      HUVECs inoculated on ZT1 compared to those on CP-Ti. However, in the later stages
      of proliferation and differentiation, the HUVECs inoculated on ZT1 were
      significantly better than the cells cultured on CP-Ti. In the oral mucosa
      irritation test, we sutured sample discs into the cheek pouch of hamsters. After
      2, 3, and 4weeks, we harvested the corresponding mucosal tissues, stained them
      with hematoxylin and eosin, obtained blood samples for biochemical analysis, and
      finally, observed the topography of the sample discs by SEM. Immunohistochemistry
      and hematology analyses showed no differences in the biocompatibility of ZT1 and
      CP-Ti, and neither of these compounds caused irritation of the mucosa. In
      addition, SEM images showed that no pitting occurred on the sample discs.
      Together, these data indicate that ZT1 may be a good candidate for dental
      implants and should be further studied.

PMID- 24857481
TI  - Biodegradable electrospun nanofibers coated with platelet-rich plasma for cell
      adhesion and proliferation.
AB  - Biodegradable electrospun poly(epsilon-caprolactone) (PCL) scaffolds were coated
      with platelet-rich plasma (PRP) to improve cell adhesion and proliferation. PRP
      was obtained from human buffy coat, and tested on human adipose-derived
      mesenchymal stem cells (MSCs) to confirm cell proliferation and
      cytocompatibility. Then, PRP was adsorbed on the PCL scaffolds via
      lyophilization, which resulted in a uniform sponge-like coating of 2.85 (S.D.
      0.14) mg/mg. The scaffolds were evaluated regarding mechanical properties
      (Young's modulus, tensile stress and tensile strain), sustained release of total
      protein and growth factors (PDGF-BB, TGF-beta1 and VEGF), and hemocompatibility.
      MSC seeded on the PRP-PCL nanofibers showed an increased adhesion and
      proliferation compared to pristine PCL fibers. Moreover, the adsorbed PRP enabled
      angiogenesis features observed as neovascularization in a chicken chorioallantoic
      membrane (CAM) model. Overall, these results suggest that PRP-PCL scaffolds hold
      promise for tissue regeneration applications.

PMID- 24857483
TI  - In vitro culture and oxygen consumption of NSCs in size-controlled neurospheres
      of Ca-alginate/gelatin microbead.
AB  - Neural stem cells (NSCs) forming neurospheres in a conventional culture tend to
      develop necrotic/apoptotic centers due to mass transport limitations. In this
      study, the internal pore structure of calcium-alginate/gelatin (CAG) microbeads
      was tuned and controlled to provide a suitable three-dimensional environment
      supporting NSC proliferation. Direct impact of three-dimensional space
      availability was quantified by oxygen consumption rates of NSCs and cells were
      cultured in three different methods: neurospheres, single cell suspension of
      NSCs, and encapsulated NSCs in microbeads. Our results showed that encapsulated
      NSCs in CAG microbeads maintained higher cell viability than in conventional
      culture. In addition, NSCs encapsulated in CAG microbeads preserved their
      original stemness and continued to express nestin, CNPase, GFAP and beta-tubulin
      III post-encapsulation. Oxygen consumption rates of encapsulated NSCs in CAG
      microbeads were the lowest as compared to the other two culture methods. The
      optimal cell density supporting high cell proliferation in CAG microbeads was
      found to be 1.5*10(5)cells/mL. The glucose consumption curve suggests that
      encapsulated NSCs in microbeads had a slower growth profile. This study presents
      an alternative method in hybrid microbead preparation to generate a highly
      favorable three-dimensional cell carrier for NSCs and was successfully applied
      for its effective in vitro expansion.

PMID- 24857484
TI  - Fabrication of gallium hexacyanoferrate modified carbon ionic liquid paste
      electrode for sensitive determination of hydrogen peroxide and glucose.
AB  - Gallium hexacyanoferrate (GaHCFe) and graphite powder were homogeneously
      dispersed into n-dodecylpyridinium hexafluorophosphate and paraffin to fabricate
      GaHCFe modified carbon ionic liquid paste electrode (CILPE). Mixture experimental
      design was employed to optimize the fabrication of GaHCFe modified CILPE (GaHCFe
      CILPE). A pair of well-defined redox peaks due to the redox reaction of GaHCFe
      through one-electron process was observed for the fabricated electrode. The
      fabricated GaHCFe-CILPE exhibited good electrocatalytic activity towards
      reduction and oxidation of H2O2. The observed sensitivities for the
      electrocatalytic oxidation and reduction of H2O2 at the operating potentials of
      +0.8 and -0.2V were about 13.8 and 18.3 mA M(-1), respectively. The detection
      limit (S/N=3) for H2O2 was about 1 MUM. Additionally, glucose oxidase (GOx) was
      immobilized on GaHCFe-CILPE using two methodology, entrapment into Nafion matrix
      and cross-linking with glutaraldehyde and bovine serum albumin, in order to
      fabricate glucose biosensor. Linear dynamic rage, sensitivity and detection limit
      for glucose obtained by the biosensor fabricated using cross-linking methodology
      were 0.1-6mM, 0.87 mA M(-1) and 30 MUM, respectively and better than those
      obtained (0.2-6mM, 0.12 mA M(-1) and 50 MUM) for the biosensor fabricated using
      entrapment methodology.

PMID- 24857485
TI  - A study on the long term effect of biofilm produced by biosurfactant producing
      microbe on medical implant.
AB  - Low density polyethylene (LDPE) is used as a long term medical implant. Biofilm
      forming ability of two pathogenic microorganisms, namely, Bacillus subtilis (B.
      subtilis) and Pseudomonas aeruginosa (P. aeruginosa) on this polymer and the
      differences in the properties of these matrices are studied for a year. There are
      very few long term studies on biofilms formed on medical implants. After three
      months, colonies of B. subtilis were two times higher when compared to those of
      P. aeruginosa. And at the end of one year, they were two orders of magnitude
      higher than the later. The exopolysaccharide (EPS) and biosurfactant recovered
      from the polymer surface after three months were 21 and 10.4 MUg/cm(2) for B.
      subtilis and 13 and 8.6 MUg/cm(2) for P. aeruginosa. After one year, these were
      higher in B. subtilis (50 and 37.1 MUg/cm(2), respectively) than in P. aeruginosa
      (34.1 and 31.8 MUg/cm(2), respectively). B. subtilis consisted of protein
      controlling the community and sporulation development, while P. aeruginosa had
      either housekeeping or metabolic proteins. The EPS in the respective biofilm
      consisted of biosurfactants produced by B. subtilis (surfactins, m/z=1029 to
      1134) and P. aeruginosa (rhamnolipids, m/z=568 to 705). Thermogravimetric
      analysis indicated that LDPE incubated with these organisms underwent a weight
      loss of 4 and 3% after three months and 11.1 and 9.2% after one year,
      respectively at 435  degrees C. Laccase and manganese peroxidase were detected in
      the biofilm which could be involved in the degradation. The biosurfactant of
      these microorganisms altered the hydrophobicity of the surface, favoring their
      attachment and proliferation.

PMID- 24857486
TI  - Creep of trabecular bone from the human proximal tibia.
AB  - Creep is the deformation that occurs under a prolonged, sustained load and can
      lead to permanent damage in bone. Creep in bone is a complex phenomenon and
      varies with type of loading and local mechanical properties. Human trabecular
      bone samples from proximal tibia were harvested from a 71-year old female cadaver
      with osteoporosis. The samples were initially subjected to one cycle load up to
      1% strain to determine the creep load. Samples were then loaded in compression
      under a constant stress for 2h and immediately unloaded. All tests were conducted
      with the specimens soaked in phosphate buffered saline with proteinase inhibitors
      at 37  degrees C. Steady state creep rate and final creep strain were estimated
      from mechanical testing and compared with published data. The steady state creep
      rate correlated well with values obtained from bovine tibial and human vertebral
      trabecular bone, and was higher for lower density samples. Tissue architecture
      was analyzed by micro-computed tomography (MUCT) both before and after creep
      testing to assess creep deformation and damage accumulated. Quantitative
      morphometric analysis indicated that creep induced changes in trabecular
      separation and the structural model index. A main mode of deformation was bending
      of trabeculae.

PMID- 24857487
TI  - Fluorescent boronic acid terminated polymer grafted silica particles synthesized
      via click chemistry for affinity separation of saccharides.
AB  - Boronic acids are important for effective separation of biological active cis
      diols. For the purpose of constructing a new type of saccharide-sensitive
      material which can not only provide convenient separation but also improve the
      access of boronic acid to guest molecules, the fluorogenic boronic acid
      terminated, thermo-sensitive polymers (BA-polyNIPAm) were grafted to an alkyne
      modified silica gel through the exploitation of click chemistry. The BA-polyNIPAm
      grafted silica gel (BA-polyNIPAm-SG) was characterized by FT-IR, fluorescence
      spectra, fluorescence microscopy, elemental analysis (EA), thermal gravimetric
      analysis (TGA), scanning electron microscope (SEM) and so on. BA-polyNIPAm-SG
      displayed affinity binding ability for saccharides under physiological pH value
      and allowed saccharides to be conveniently separated from solution. The maximum
      binding capacities for fructose and glucose are 83.2 MUmol/g and 70.4 MUmol/g
      polymer, respectively. The intensity of fluorescence emission of BA-polyNIPAm-SG
      increased with the increasing of fructose concentration. The present study
      provides a new kind of composite material which contains moveable and flexible
      grippers for recognizing and binding guest molecules.

PMID- 24857488
TI  - Direct electrochemistry and electrocatalysis of hemoglobin in graphene oxide and
      ionic liquid composite film.
AB  - In this paper a novel sensing platform based on graphene oxide (GO), ionic liquid
      (IL) 1-ethyl-3-methylimidazolium tetrafluoroborate and Nafion for the
      immobilization of hemoglobin (Hb) was adopted with a carbon ionic liquid
      electrode (CILE) as the substrate electrode, which was denoted as Nafion/Hb-GO
      IL/CILE. Spectroscopic results suggested that Hb molecules were not denatured in
      the composite. A pair of well-defined redox peaks appeared on the cyclic
      voltammogram, which was attributed to the realization of direct electron transfer
      of Hb on the electrode. Electrochemical behaviors of Hb entrapped in the film
      were carefully investigated by cyclic voltammetry with the electrochemical
      parameters calculated. Based on the catalytic ability of the immobilized Hb,
      Nafion/Hb-GO-IL/CILE exhibited excellent electrocatalytic behavior towards the
      reduction of different substrates such as trichloroacetic acid in the
      concentration range from 0.01 to 40.0mM with the detection limit as 3.12 MUM
      (3sigma), H2O2 in the concentration range from 0.08 to 635.0 MUM with the
      detection limit as 0.0137 MUM (3sigma) and NaNO2 in the concentration range from
      0.5 to 800.0 MUM with the detection limit as 0.0104 MUM (3sigma). So the proposed
      bioelectrode could be served as a new third-generation electrochemical sensor
      without mediator.

PMID- 24857489
TI  - PLA/chitosan/keratin composites for biomedical applications.
AB  - Novel composites based on PLA, chitosan and keratin was obtained via blend
      preparation. The goal of this contribution was to evaluate mechanical and in
      vitro behavior of the composites. The results point out composites with improved
      Young modulus and decreased tensile strength, significant increase in hardness
      (compared to PLA) and a good uptake of the surface properties. Biological
      assessments using human osteosarcoma cell line on these composites indicate a
      good viability/proliferation outcome. Hence preliminary results regarding
      mechanical behavior and in vitro osteoblast response suggest that these
      composites might have prospective application in medical field. 

PMID- 24857490
TI  - Synthesis of 45S5 Bioglass(r) via a straightforward organic, nitrate-free sol-gel
      process.
AB  - More than four decades after the discovery of 45S5 Bioglass(r) as the first
      bioactive material, this composition is still one of the most promising materials
      in the tissue engineering field. Sol-gel-derived bioactive glasses generally
      possess improved properties over other bioactive glasses, because of their highly
      porous microstructure and unique surface chemistry which accelerate
      hydroxyapatite formation. In the current study, a new combination of precursors
      with lactic acid as the hydrolysis catalyst have been employed to design an
      organic, nitrate-free sol-gel procedure for synthesizing of 45S5 Bioglass(r).
      This straightforward route is able to produce fully amorphous submicron particles
      of this glass with an appropriately high specific surface area on the order of
      ten times higher than that of the melt-derived glasses. These characteristics are
      expected to lead to rapid hydroxyapatite formation and consequently more
      efficient bone bonding.

PMID- 24857491
TI  - Biological evaluation of zirconia/PEG hybrid materials synthesized via sol-gel
      technique.
AB  - The objective of the following study has been the synthesis via sol-gel and the
      characterization of novel organic-inorganic hybrid materials to be used in
      biomedical field. The prepared materials consist of an inorganic zirconia matrix
      containing as organic component the polyethylene glycol (PEG), a water-soluble
      polymer used in medical and pharmaceutical fields. Various hybrids have been
      synthesized changing the molar ratio between the organic and inorganic parts.
      Fourier transform spectroscopy suggests that the structure of the
      interpenetrating network is realized by hydrogen bonds between the Zr-OH group in
      the sol-gel intermediate species and both the terminal alcoholic group and
      ethereal oxygen atoms in the repeating units of polymer The amorphous nature of
      the gels has been ascertained by X-ray diffraction analysis. The morphology
      observation has been carried out by using the Scanning Electron Microscope and
      has confirmed that the obtained materials are nanostructurated hybrids. The
      bioactivity of the synthesized system has been shown by the formation of a
      hydroxyapatite layer on the surface of samples soaked in a fluid simulating the
      human blood plasma. The potential biocompatibility of hybrids has been assessed
      as performing indirect MTT cytotoxicity assay towards 3T3 cell line at 24, 48,
      and 72 h exposure times.

PMID- 24857492
TI  - Evaluation of the biological effects of 5-Cl-8-oxyquinolinepropoxycalix[4]arene
      and 8-oxyquinolinepropoxycalix[4]arene in vitro and in vivo.
AB  - The development of antibacterial and antifungal drugs has been the target of
      several pharmaceutical and chemical industries mainly due to the lack of
      effective drugs with low or no side effect. In this work, studies were conducted
      both in vitro and in vivo with 8-oxyquinolinepropoxycalix[4]arene (A) and 5-Cl-8
      oxyquinolinepropoxycalix[4]arene (B) ligands, showing fairly good results.
      Cytotoxicity and fungicidal actions of compounds A and B were determined in
      Wistar male rats and peritoneal macrophages of mice. A slight change in the total
      of leukocytes and erythrocytes was observed on the hematologic assays, showing
      almost no inflammation after using both compounds in Wistar male rats. We have
      also noted some, but not significant, alteration in liver enzymes representing
      modest hepatotoxicity. Cytotoxicity of peritoneal macrophages, in the presence of
      compound A or B, showed 50% of survival of macrophages. On the other hand,
      macrophages previously infected with Candida albicans and treated with substance
      A or B exhibited an increased cytokine IL-10 at 24h incubation. By checking the
      effect of substance A or B on growing C. albicans, the results pointed that these
      substances revealed antifungal activity against C. albicans, in 24h culture with
      a reduction of yeast cells.

PMID- 24857493
TI  - Unlocked and locked elastic stable intramedullary nailing in an ovine tibia
      fracture model: a biomechanical study.
AB  - In the present study, four different systems of elastic stable intramedullary
      nails (unlocked, Ender stainless steel nails locked with 3-mm screws, titanium
      nails locked with end caps, titanium nails locked with plugs and 3-mm screws)
      were implanted in cadaveric ovine tibiae. Fractures were simulated by a
      transverse diaphyseal osteotomy. The specimens were subjected to simultaneous
      axial and torsional fatigue loading of 5000 and 1000 cycles, respectively. The
      unlocked systems failed at an axial load of 200 N peak amplitude. End caps
      systems withstood axial loads up to 800 N for 1000 cycles, and ender nails and
      plugs lasted up to 1000 N for 1000 cycles. All systems showed a decrease of axial
      stiffness with higher loads and endured cycles. Ender nails and nails locked with
      plugs failed by penetration of the distal epiphysis rather than by loosening of
      the interlocking system. Overall, the titanium nails locked with plugs and 3-mm
      screws exhibited superior test results.

PMID- 24857494
TI  - Magnetic solid-phase extraction based on mesoporous silica-coated magnetic
      nanoparticles for analysis of oral antidiabetic drugs in human plasma.
AB  - In the present work, magnetic nanoparticles embedded into mesoporous silica were
      prepared in two steps: first, magnetite was synthesized by oxidation
      precipitation method, and next, the magnetic nanoparticles were coated with
      mesoporous silica by using nonionic block copolymer surfactants as structure
      directing agents. The mesoporous SiO2-coated Fe3O4 samples were functionalized
      using octadecyltrimethoxysilane as silanizing agent. The pure and functionalized
      silica nanoparticles were physicochemically and morphologically characterized by
      X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), N2
      adsorption, scanning electron microscopy (SEM) and transmission electron
      microscopy (TEM). The resultant magnetic silica nanoparticles were applied as
      sorbents for magnetic solid-phase extraction (MSPE) of oral antidiabetic drugs in
      human plasma. Our results revealed that the magnetite nanoparticles were
      completely coated by well-ordered mesoporous silica with free pores and stable
      pore walls, and that the structural and magnetic properties of the Fe3O4
      nanoparticles were preserved in the applied synthesis route. Indeed, the sorbent
      material was capable of extracting the antidiabetic drugs from human plasma,
      being useful for the sample preparation in biological matrices.

PMID- 24857495
TI  - Effect of natamycin, nisin and glycerol on the physicochemical properties,
      roughness and hydrophobicity of tapioca starch edible films.
AB  - In this paper, films based on tapioca starch and containing nisin, natamycin and
      glycerol were characterized in relation to their physicochemical properties,
      roughness and hydrophobicity. The content of glycerol affected the mechanical
      properties of the films studied and the roughness and it was observed an increase
      in WVP with the increase in glycerol content. The addition of antimicrobials
      affected the mechanical properties, being nisin the one that produced the greater
      decrease in the Young modulus. The color was highly affected by the joint
      presence of natamycin and nisin, which increased the yellow index. The contact
      angle increased with antimicrobial addition indicating a decrease in
      hydrophilicity. Nisin also affected the roughness of the films. Water vapor
      permeability was slightly reduced by the presence of natamycin. It was observed
      that water vapor permeability and contact angle were correlated with the
      roughness of the films. 

PMID- 24857496
TI  - Particle size and shape modification of hydroxyapatite nanostructures synthesized
      via a complexing agent-assisted route.
AB  - In this work, hydroxyapatite (HAP), Ca10(PO4)6(OH)2, nanostructures including
      nanorods, nanobundles and nanoparticles have been prepared via a simple
      precipitation method. In the present method, Ca(NO3)2.4H2O and (NH4)2HPO4 were
      used as calcium and phosphorus precursors, respectively. Besides, the Schiff
      bases derived from 2-hydroxyacetophenone and different diamines were used as
      complexing agents for the in situ formation of Ca(2+) complexes. The formation
      mechanism of 0-D and 1-D nanostructures of HAP was also considered. When the
      complexing agents could coordinate to the Ca(2+) ions through N and O atoms to
      form the [CaN2O2](2+) complexes, HAP nanoparticles were generated. On the other
      hand, nanorods and nanobundles of HAP were obtained by forming the [CaN2](2+) as
      well as [CaO2](2+) complexes in the reaction solution. This work is the first
      successful synthesis of pure HAP nanostructures in the presence of Schiff bases
      instead of using the common surfactants. 

PMID- 24857497
TI  - Utilization of highly purified single wall carbon nanotubes dispersed in polymer
      thin films for an improved performance of an electrochemical glucose sensor.
AB  - In this work we report the improved performance an electrochemical glucose sensor
      based on a glassy carbon electrode (GCE) that has been modified with highly
      purified single wall carbon nanotubes (SWCNTs) dispersed in polyethyleneimine
      (PEI), polyethylene glycol (PEG) and polypyrrole (PPy). The single wall carbon
      nanotubes were purified by both thermal and chemical oxidation to achieve maximum
      purity of ~98% with no damage to the tubes. The SWCNTs were then dispersed by
      sonication in three different organic polymers (1.0mg/ml SWCNT in 1.0mg/ml of
      organic polymer). The stable suspension was coated onto the GCE and
      electrochemical characterization was performed by Cyclic Voltammetry (CV) and
      Amperometry. The electroactive enzyme glucose oxidase (GOx) was immobilized on
      the surface of the GCE/(organic polymer-SWCNT) electrode. The amperometric
      detection of glucose was carried out at 0.7 V versus Ag/AgCl. The GCE/(SWCNT-PEI,
      PEG, PPY) gave a detection limit of 0.2,633 MUM, 0.434 MUM, and 0.9,617 MUM, and
      sensitivities of 0.2411 +/- 0.0033 MUA mM(-1), r(2)=0.9984, 0.08164 +/- 0.001129
      MUA mM(-1), r(2)=0.9975, 0.04189 +/- 0.00087 MUA mM(-1), and r(2)=0.9944
      respectively and a response time of less than 5s. The use of purified SWCNTs has
      several advantages, including fast electron transfer rate and stability in the
      immobilized enzyme. The significant enhancement of the SWCNT modified electrode
      as a glucose sensor can be attributed to the superior conductivity and large
      surface area of the well dispersed purified SWCNTs.

PMID- 24857498
TI  - PEGylation of magnetic poly(glycidyl methacrylate) microparticles for
      microfluidic bioassays.
AB  - In this study, magnetic poly(glycidyl methacrylate) microparticles containing
      carboxyl groups (PGMA-COOH) were coated using highly hydrophilic polymer
      poly(ethylene glycol) (PEG). PEG was used to reduce nonspecific interactions with
      proteins and cells while decreasing adhesion of particles to the walls of a
      microfluidic devices from poly(dimethylsiloxane) (PDMS) and cyclic olefin
      copolymer (COC). Zeta potential measurement, infrared spectroscopy, scanning
      electron microscopy, anti-PEG ELISA assay, and bioaffinity interactions between
      biotin and streptavidin-HRP successfully proved the presence of PEG on the
      surface of microspheres. Both neat and PEGylated microspheres were then incubated
      with the inert protein bovine serum albumin or cells to evaluate the rate of
      nonspecific adsorption (NSA). PEG with Mr of 30,000 Da was responsible for 45%
      reduction in NSA of proteins and 74% for cells compared to neat particles. The
      microspheres' behavior in PDMS and COC microchannels was then evaluated.
      Aggregation and adhesion of PEGylated microspheres significantly decreased
      compared to neat particles. Finally, the model enzyme horseradish peroxidase was
      immobilized on the microspheres through the heterobifunctional PEG chain. The
      possibility for subsequent covalent coupling of the ligand of interest was
      confirmed. Such PEGylated microparticles can be efficiently used in PDMS
      microchips as a carrier for bioaffinity separation or of enzyme for catalysis.

PMID- 24857499
TI  - Effects of substrate stiffness on adipogenic and osteogenic differentiation of
      human mesenchymal stem cells.
AB  - Substrate mechanical properties, in addition to biochemical signals, have been
      shown to modulate cell phenotype. In this study, we inspected the effects of
      substrate stiffness on human mesenchymal stem cells (hMSCs) derived from adult
      human bone marrow differentiation into adipogenic and osteogenic cells. A
      chemically modified extracellular matrix derived and highly biocompatible
      hydrogel, based on thiol functionalized hyaluronic acid (HA-SH) and thiol
      functionalized recombinant human gelatin (Gtn-SH), which can be crosslinked by
      poly (ethylene glycol) tetra-acrylate (PEGTA), was used as a model system. The
      stiffness of the hydrogel was controlled by adjusting the crosslinking density.
      Human bone marrow MSCs were cultured on the hydrogels with different stiffness
      under adipogenic and osteogenic conditions. Oil Red O staining and F-actin
      staining were applied to assess the change of cell morphologies under adipogenic
      and osteogenic differentiation, respectively. Gene expression of cells was
      determined with reverse transcription polymerase chain reaction (RT-PCR) as a
      function of hydrogel stiffness. Results support the hypothesis that adipogenic
      and osteogenic differentiation of hMSCs are inclined to occur on substrate with
      stiffness similar to their in vivo microenvironments. 

PMID- 24857500
TI  - Mechanically-reinforced electrospun composite silk fibroin nanofibers containing
      hydroxyapatite nanoparticles.
AB  - Electrospun silk fibroin (SF) scaffolds provide large surface area, high
      porosity, and interconnection for cell adhesion and proliferation and they may
      replace collagen for many tissue engineering applications. Despite such
      advantages, electrospun SF scaffolds are still limited as bone tissue replacement
      due to their low mechanical strengths. While enhancement of mechanical strengths
      by incorporating inorganic ceramics into polymers has been demonstrated,
      electrospinning of a mixture of SF and inorganic ceramics such as hydroxyapatite
      is challenging and less studied due to the aggregation of ceramic particles
      within SF. In this study, we aimed to enhance the mechanical properties of
      electrospun SF scaffolds by uniformly dispersing hydroxyapatite (HAp)
      nanoparticles within SF nanofibers. HAp nanoaprticles were modified by gamma
      glycidoxypropyltrimethoxysilane (GPTMS) for uniform dispersion and enhanced
      interfacial bonding between HAp and SF fibers. Optimal conditions for
      electrospinning of SF and GPTMS-modified HAp nanoparticles were identified to
      achieve beadless nanofibers without any aggregation of HAp nanoparticles. The MTT
      and SEM analysis of the osteoblasts-cultured scaffolds confirmed the
      biocompatibility of the composite scaffolds. The mechanical properties of the
      composite scaffolds were analyzed by tensile tests for the scaffolds with varying
      contents of HAp within SF fibers. The mechanical testing showed the peak
      strengths at the HAp content of 20 wt.%. The increase of HAp content up to 20
      wt.% increased the mechanical properties of the composite scaffolds, while
      further increase above 20 wt.% disrupted the polymer chain networks within SF
      nanofibers and weakened the mechanical strengths.

PMID- 24857501
TI  - Locust bean gum as an alternative polymeric coating for embryonic stem cell
      culture.
AB  - Pluripotent embryonic stem cells (ESCs) have self-renewal capacity and the
      potential to differentiate into any cellular type depending on specific cues
      (pluripotency) and, therefore, have become a vibrant research area in the
      biomedical field. ESCs are usually cultured in gelatin or on top of a monolayer
      of feeder cells such as mitotically inactivated mouse embryonic fibroblasts
      (MEFsi). The latter is the gold standard support to maintain the ESCs in the
      pluripotent state. Examples of versatile, non-animal derived and inexpensive
      materials that are able to support pluripotent ESCs are limited. Therefore, our
      aim was to find a biomaterial able to support ESC growth in a pluripotent state
      avoiding laborious and time consuming parallel culture of MEFsi and as simple to
      handle as gelatin. Many of the new biomaterials used to develop stem cell
      microenvironments are using natural polymers adsorbed or covalently attached to
      the surface to improve the biocompatibility of synthetic polymers. Locust beam
      gum (LBG) is a natural, edible polymer, which has a wide range of potential
      applications in different fields, such as food and pharmaceutical industry, due
      to its biocompatibility, adhesiveness and thickening properties. The present work
      brings a natural system based on the use of LBG as a coating for ESC culture.
      Undifferentiated mouse ESCs were cultured on commercially available LBG to
      evaluate its potential in maintaining pluripotent ESCs. In terms of morphology,
      ESC colonies in LBG presented the regular dome shape with bright borders, similar
      to the colonies obtained in co-cultures with MEFsi and characteristic of
      pluripotent ESC colonies. In short-term cultures, ESC proliferation in LBG
      coating was similar to ESC cultured in gelatin and the cells maintained their
      viability. The activity of alkaline phosphatase and Nanog, Sox2 and Oct4
      expression of mouse ESCs cultured in LBG were comparable or in some cases higher
      than in ESCs cultured in gelatin. An in vitro differentiation assay revealed that
      mouse ESCs cultured in LBG preserve their tri-lineage differentiation capacity.
      In conclusion, our data indicate that LBG coating promotes mouse ESC growth in an
      undifferentiated state demonstrating to be a viable, non-animal derived
      alternative to gelatin to support pluripotent mouse ESCs in culture.

PMID- 24857502
TI  - Enhanced gastric tolerability and improved anti-obesity effect of capsaicinoids
      loaded PCL microparticles.
AB  - Capsaicinoids show several pharmacological effects including weight loss.
      However, their pungency limits the long-term use through the gastrointestinal
      tract. In that sense, the goal of this study was to prepare capsaicinoids-loaded
      poly(epsilon-caprolactone) microparticles as an oral carrier in order to improve
      their gastric tolerability and to make feasible the long-term treatment of
      obesity. Formulations containing 3, 5 and 10% capsaicinoids were successfully
      obtained by simple emulsion/solvent evaporation method. Values of encapsulation
      efficiency above 90% were achieved. Microparticles showed spherical shape and
      smooth surface. The particle size was suitable for oral use in order to provide
      an extended release through the gastrointestinal tract. No chemical bond was
      observed between drug and polymer. Microencapsulation led to drug amorphization.
      Formulations prolonged the release of capsaicinoids without changing the release
      kinetic (biexponential model). Microencapsulation increased the gastric
      tolerability of capsaicinoids because it prevented inflammatory processes in the
      stomach of rats. Microparticles containing 5% capsaicinoids demonstrated a
      statistically significant reduction of Lee index, mesenteric and retroperitoneal
      fat pads of rats with obesity induced by hypothalamic lesion using monosodium l
      glutamate. In summary, capsaicinoids-loaded poly(epsilon-caprolactone)
      microparticles are low-irritative oral controlled-release carriers for a long
      term use in obesity.

PMID- 24857503
TI  - A study of strontium doped calcium phosphate coatings on AZ31.
AB  - Calcium phosphate (CaP) coatings have been studied to tailor the uncontrolled non
      uniform corrosion of Mg based alloys while simultaneously enhancing bioactivity.
      The use of immersion techniques to deposit CaP coatings is attractive due to the
      ability of the approach to coat complex structures. In the current study, AZ31
      substrates were subjected to various pretreatment conditions prior to depositing
      Sr(2+) doped and undoped CaP coatings. It was hypothesized that the bioactivity
      and corrosion protection of CaP coatings could be improved by doping with Sr(2+).
      Heat treatment to elevated temperatures resulted in the diffusion of alloying
      elements, Mg and Zn, into the pretreated layer. Sr(2+) doped and undoped CaP
      coatings formed on the pretreated substrates consisted of biphasic mixtures of
      beta-tricalcium phosphate (beta-TCP) and hydroxyapatite (HA). Electrochemical
      corrosion experiments indicated that the extent of Sr(2+) doping and pretreatment
      both influenced the corrosion protection. Cytotoxicity was evaluated with MC3T3
      E1 mouse preosteoblasts and human mesenchymal stem cells (hMSCs). For both cell
      types, proliferation decreased upon increasing the Sr(2+) concentration. However,
      both osteogenic gene and protein expression significantly increased upon
      increasing Sr(2+) concentration. These results suggest that Sr(2+) doped coatings
      are capable of promoting osteogenic differentiation on degradable Mg alloys,
      while also enhancing corrosion protection, in comparison to undoped CaP coatings.

PMID- 24857504
TI  - Multifunctional tunable p(inulin) microgels.
AB  - Inulin, inulin-silica and modified inulin microgels were prepared in a single
      step via crosslinking within microemulsion, and used as drug delivery devices.
      Inulin-silica composite micro particles were also synthesized in the presence of
      tetraethyl orthosilicate (TEOS) via a water-in-oil microemulsion
      polymerization/crosslinking technique. To generate porous inulin particles,
      inulin-silica particles were treated with 0.5M NaOH solution to dissolve silica
      particles. Furthermore, virgin inulin (p(inulin)) and porous inulin microgels
      (por-p(inulin)) were quaternized successfully by treatment with 3-chloro-2
      hydroxypropyl trimethyl ammonium chloride (CHPTMAC) in aqueous solution,
      generating positive charges on the biopolymer as q-p(inulin). Rosmarinic acid
      (RA) was used as model drug for loading and release studies by synthesized inulin
      based microgels in phosphate buffer solution (PBS) at pH7.4. It was shown that
      the absorption and release rate are influenced by zeta potential and porosity of
      the microgels.

PMID- 24857505
TI  - Phosphate mineral formation on the supported dipalmitoylphosphatidylcholine
      (DPPC) layers.
AB  - Dipalmitoylphosphatidylcholine (DPPC) mono- and bilayers supported on mica
      surface were soaked for two weeks in a simulated body fluid (SBF) with ion
      concentrations nearly equal to those of human blood plasma. Two solutions were
      investigated: with and without Tris. The experiment was conducted at 20 degrees C
      and at a physiological temperature equal to 37 degrees C. Raman spectroscopy was
      used for the characterization of the precipitated phosphate minerals. These
      studies may provide information about the physiological mineralization of cell
      membranes that are mainly composed of phospholipids. Findings from these
      experiments suggest that the DPPC bilayers enhance the formation of less soluble
      phosphate forms especially at a temperature of 37 degrees C. In the solution
      without Tris temperature increase gives more mineral deposits. It is probably the
      hydrogen interactions between phosphate groups of the phospholipid and hydroxyl
      groups from Tris that lower exposure of the phosphate group to interact with
      calcium ions.

PMID- 24857506
TI  - In vitro and in vivo evaluation of a new nanocomposite, containing high density
      polyethylene, tricalcium phosphate, hydroxyapatite, and magnesium oxide
      nanoparticles.
AB  - In this study, a new nanocomposite, which contained high density polyethylene
      (HDPE), tricalcium phosphate (Ca3(PO4)2) nanoparticles (TCP NPs), hydroxyapatite
      nanoparticles (HA NPs), and magnesium oxide nanoparticles (MgO NPs) was prepared.
      As in vitro experiment, human osteoblasts (HOB) cells were exposed to pristine
      HDPE and its nanocomposite for a period of 1, 4, and 7 days at 37  degrees C, and
      then different assays were carried out, including osteoblast cell proliferation,
      Trypan blue staining, cell viability, alkaline phosphatase (ALP), and cell
      adhesion. Antibacterial property of pristine HDPE and its nanocomposite was
      evaluated, and also their mechanical properties were measured after 2 and 4
      months. As in vivo experiment, pristine HDPE and its nanocomposite were
      separately implanted on calvarium bone of rabbits, and tissue inflammation and
      osteogenesis were investigated after 2, 4, and 6 months. In case of HOB cells
      treated with HDPE or nanocomposite, as incubation time was increased, cell
      proliferation, live/dead ratio, and cell viability were decreased. But, the ALP
      activity and cell adhesion of HOB cells which treated with nanocomposite were
      raised after increase of incubation time. This study demonstrated that although
      the mechanical properties of nanocomposite were similar to HDPE sheet, but their
      antibacterial property was not similar. The in vivo experiment showed that both
      pristine HDPE and its nanocomposite had same inflammation responses.
      Interestingly, osteogenesis was observed after 2 months at bone/nanocomposite
      interface, and was highly increased after 4 and 6 months. It must be noted that
      such pattern was not seen at bone/HDPE interface.

PMID- 24857507
TI  - Surface modification of polycaprolactone scaffolds fabricated via selective laser
      sintering for cartilage tissue engineering.
AB  - Surface modified porous polycaprolactone scaffolds fabricated via rapid
      prototyping techniques were evaluated for cartilage tissue engineering purposes.
      Polycaprolactone scaffolds manufactured by selective laser sintering (SLS) were
      surface modified through immersion coating with either gelatin or collagen. Three
      groups of scaffolds were created and compared for both mechanical and biological
      properties. Surface modification with collagen or gelatin improved the
      hydrophilicity, water uptake and mechanical strength of the pristine scaffold.
      From microscopic observations and biochemical analysis, collagen-modified
      scaffold was the best for cartilage tissue engineering in terms of cell
      proliferation and extracellular matrix production. Chondrocytes/collagen-modified
      scaffold constructs were implanted subdermally in the dorsal spaces of female
      nude mice. Histological and immunohistochemical staining of the retrieved
      implants after 8 weeks revealed enhanced cartilage tissue formation. We conclude
      that collagen surface modification through immersion coating on SLS-manufactured
      scaffolds is a feasible scaffold for cartilage tissue engineering in craniofacial
      reconstruction.

PMID- 24857508
TI  - Co-immobilization of active antibiotics and cell adhesion peptides on calcium
      based biomaterials.
AB  - Two bioactive molecules with unrelated functions, vancomycin and a cell adhesion
      peptide, were immobilized on the surface of a potential bone scaffold material,
      calcium aluminum oxide. In order to accomplish immobilization and retain
      bioactivity three sequential surface functionalization strategies were compared:
      1.) vancomycin was chemically immobilized before a cell adhesion peptide (KRSR),
      2.) vancomycin was chemically immobilized after KRSR and 3.) vancomycin was
      adsorbed after binding the cell adhesion peptide. Both molecules remained on the
      surface and active using all three reaction sequences and after autoclave
      sterilization based on osteoblast attachment, bacterial turbidity and bacterial
      zone inhibition test results. However, the second strategy was superior at
      enhancing osteoblast attachment and significantly decreasing bacterial growth
      when compared to the other sequences. 

PMID- 24857509
TI  - The role of surface oxidation on the degradation behavior of biodegradable Mg-RE
      (Gd, Y, Sc) alloys for resorbable implants.
AB  - Biodegradable magnesium (Mg) alloys have the potential to replace currently used
      implants for fixation, thereby eliminating the need for removal surgeries. To
      achieve a controllable degradation rate, surface oxidation has been proposed as
      an avenue to reduce the initial degradation. This study aims to investigate the
      oxidation behavior of binary Mg-rare earth alloys and the effect on
      biodegradation. Cast Mg-3X alloys (X=Gd, Y, Sc) were prepared and then oxidized
      in pure oxygen. The oxidation rate was evaluated using TGA and the oxides were
      further investigated and characterized using SEM, AES and XPS. The effect of
      oxidation on the degradation rate was investigated by immersion testing in Hanks'
      solution. The thermodynamics and oxidation kinetics of the alloys are discussed
      in regard to the obtained results, and it was concluded that the experimental
      results are in agreement with thermodynamic predictions. 

PMID- 24857510
TI  - New porous polycaprolactone-silica composites for bone regeneration.
AB  - Polycaprolactone porous membranes were obtained by freeze extraction of dioxane
      from polycaprolactone-dioxane solid solutions. Porosities as high as 90% with
      interconnected structures were obtained by this technique. A silica phase was
      synthesized inside the pores of the polymer membrane by sol-gel reaction using
      tetraethylorthosilicate (TEOS) as a silica precursor and catalyzed in acidic and
      basic conditions. Two different morphologies of the inorganic phase were obtained
      depending on the type of catalyst. In acid catalyzed sol-gel reaction, a
      homogeneous layer of silica was deposited on the pores, and discrete microspheres
      were synthesized on the pore walls when a basic catalyst was used. The morphology
      of the inorganic phase influenced the mechanical and thermal behavior, as well as
      the hydrophilic character of the composites. Bioactivity of the porous materials
      was tested in vitro by measuring the deposition of hydroxyapatite on the surfaces
      of the porous composite membranes. Polycaprolactone/silica composites revealed a
      superior bioactivity performance compared with that of the pure polymer;
      evidenced by the characteristic cauliflower structures on the material surface,
      increase in weight and Ca/P ratio of the hydroxyapatite layer. Also, the acid
      catalyzed composites presented better bioactivity than the base catalyzed
      composites, evidencing the importance in the morphology of the silica phase. 

PMID- 24857511
TI  - Exploring the elasticity and adhesion behavior of cardiac fibroblasts by atomic
      force microscopy indentation.
AB  - AFM was used to collect the whole force-deformation cell curves. They provide
      both the elasticity and adhesion behavior of mouse primary cardiac fibroblasts.
      To confirm the hypothesis that a link exists between the membrane receptors and
      the cytoskeletal filaments causing therefore changing in both elasticity and
      adhesion behavior, actin-destabilizing Cytochalsin D was administrated to the
      fibroblasts. From immunofluorescence observation and AFM loading/unloading
      curves, cytoskeletal reorganization as well as a change in the elasticity and
      adhesion was indeed observed. Elasticity of control fibroblasts is three times
      higher than that for fibroblasts treated with 0.5 MUM Cytochalasin. Moreover, AFM
      loading-unloading curves clearly show the different mechanical behavior of the
      two different cells analyzed: (i) for control cells the AFM cantilever rises
      during the dwell time while cells with Cytochalasin fail to show such an active
      resistance; (ii) the maximum force to deform control cells is quite higher and as
      far as adhesion is concern (iii) the maximum separation force, detachment area
      and the detachment process time are much larger for control compared to the
      Cytochalasin treated cells. Therefore, alterations in the cytoskeleton suggest
      that a link must exist between the membrane receptors and the cytoskeletal
      filaments beneath the cellular surface and inhibition of actin polymerization has
      effects on the whole cell mechanical behavior as well as adhesion.

PMID- 24857512
TI  - Ion release and surface oxide composition of AISI 316L, Co-28Cr-6Mo, and Ti-6Al
      4V alloys immersed in human serum albumin solutions.
AB  - The long-term weight loss, ion release, and surface composition of 316L, Co-28Cr
      6Mo and Ti-6Al-4V alloys were investigated in a simulated body environment. The
      samples were immersed in phosphate-buffered saline (PBS) solutions with various
      human serum albumin (HSA) concentrations for 8, 14, and 22 weeks. The specimens
      initially lost weight up to 14 weeks and then slightly gained weight. The
      analysis of the released ions was performed by induced coupled plasma-optical
      emission spectrometer (ICP-OES). The results revealed that the precipitation of
      the dissolved Fe and Co could cause the weight gain of the 316L and Co-28Cr-6Mo
      alloys. The surface chemistry of the specimens was determined by X-ray
      photoelectron spectroscopy (XPS). The XPS analysis of Co-28Cr-6Mo alloy showed
      that the interaction of Mo with HSA is different from Mo with bovine serum
      albumin (BSA). This was also observed for Na adsorption into the oxide layer of
      Ti-6Al-4V alloy in the presence of HSA and BSA.

PMID- 24857513
TI  - Enhanced chondrogenesis of human nasal septum derived progenitors on nanofibrous
      scaffolds.
AB  - Topographical cues can be exploited to regulate stem cell attachment,
      proliferation, differentiation and function in vitro and in vivo. In this study,
      we aimed to investigate the influence of different nanofibrous topographies on
      the chondrogenic differentiation potential of nasal septum derived progenitors
      (NSP) in vitro. Aligned and randomly oriented Ploy (l-lactide)
      (PLLA)/Polycaprolactone (PCL) hybrid scaffolds were fabricated via
      electrospinning. First, scaffolds were fully characterized, and then NSP were
      seeded on them to study their capacity to support stem cell attachment,
      proliferation and chondrogenic differentiation. Compared to randomly oriented
      nanofibers, aligned scaffolds showed a high degree of nanofiber alignment with
      much better tensile strength properties. Both scaffolds supported NSP adhesion,
      proliferation and chondrogenic differentiation. Despite the higher rate of cell
      proliferation on random scaffolds, a better chondrogenic differentiation was
      observed on aligned nanofibers as deduced from higher expression of chondrogenic
      markers such as collagen type II and aggrecan on aligned scaffolds. These
      findings demonstrate that electrospun constructs maintain NSP proliferation and
      differentiation, and that the aligned nanofibrous scaffolds can significantly
      enhance chondrogenic differentiation of nasal septum derived progenitors.

PMID- 24857514
TI  - In-vitro long term and electrochemical corrosion resistance of cold deformed
      nitrogen containing austenitic stainless steels in simulated body fluid.
AB  - This work was focused on the evaluation of the corrosion behavior of deformed
      (10% and 20% cold work) and annealed (at 1050  degrees C for 15 min followed by
      water quenching) Ni-free high nitrogen austenitic stainless steels (HNSs) in
      simulated body fluid at 37 degrees C using weight loss method (long term),
      electrochemical impedance spectroscopy (EIS) and potentiodynamic polarization.
      Scanning electron microscopy (SEM) was used to understand the surface morphology
      of the alloys after polarization test. It has been observed that cold working had
      a significant influence on the corrosion resistant properties of these alloys.
      The weight loss and corrosion rates were observed to decrease with increasing
      degree of cold working and nitrogen content in the alloy. The corrosion
      resistance of the material is directly related to the resistance of the passive
      oxide film formed on its surface which was enhanced with cold working and
      nitrogen content. It was also observed that corrosion current densities were
      decreased and corrosion potentials were shifted to more positive values. By
      seeing pit morphology under SEM, shallower and smaller pits were associated with
      HNSs and cold worked samples, indicating that corrosion resistance increases with
      increasing nitrogen content and degree of cold deformation. X-ray diffraction
      profiles of annealed as well as deformed alloys were revealed and there is no
      evidence for formation of martensite or any other secondary phases.

PMID- 24857515
TI  - Intramolecular proton transfer through the adjoining pi-conjugated system in
      Shiff base: application for colorimetric sensing of fluoride anion.
AB  - In this paper, a new kind of phenol-based chemsensor L2 comprised of a Schiff
      base and azo groups was rationally designed and synthesized. It could selectively
      recognize fluoride anion among tested anions such as F(-), AcO(-), H2PO4(-), Cl(
      ), Br(-), and I(-) with obvious color changes from yellow to fuchsia. The
      intramolecular PT (proton transfer) in L1 and L2 was responsible for the sensing
      ability, which was certified by the (1)H NMR and Uv-vis experiments.

PMID- 24857516
TI  - Systematic reviews of and integrated report on the quantitative, qualitative and
      economic evidence base for the management of obesity in men.
AB  - BACKGROUND: Obesity increases the risk of many serious illnesses such as coronary
      heart disease, type 2 diabetes and osteoarthritis. More men than women are
      overweight or obese in the UK but men are less likely to perceive their weight as
      a problem and less likely to engage with weight-loss services. OBJECTIVE: The aim
      of this study was to systematically review evidence-based management strategies
      for treating obesity in men and investigate how to engage men in obesity services
      by integrating the quantitative, qualitative and health economic evidence base.
      DATA SOURCES: Electronic databases including MEDLINE, EMBASE, PsycINFO, the
      Cochrane Central Register of Controlled Trials, the Database of Abstracts of
      Reviews of Effects and the NHS Economic Evaluation Database were searched from
      inception to January 2012, with a limited update search in July 2012. Subject
      specific websites, reference lists and professional health-care and commercial
      organisations were also consulted. REVIEW METHODS: Six systematic reviews were
      conducted to consider the clinical effectiveness, cost-effectiveness and
      qualitative evidence on interventions for treating obesity in men, and men in
      contrast to women, and the effectiveness of interventions to engage men in their
      weight reduction. Randomised controlled trials (RCTs) with follow-up data of at
      least 1 year, or any study design and length of follow-up for UK studies, were
      included. Qualitative and mixed-method studies linked to RCTs and non-randomised
      intervention studies, and UK-based, men-only qualitative studies not linked to
      interventions were included. One reviewer extracted data from the included
      studies and a second reviewer checked data for omissions or inaccuracies. Two
      reviewers carried out quality assessment. We undertook meta-analysis of
      quantitative data and a realist approach to integrating the qualitative and
      quantitative evidence synthesis. RESULTS: From a total of 12,764 titles reviewed,
      33 RCTs with 12 linked reports, 24 non-randomised reports, five economic
      evaluations with two linked reports, and 22 qualitative studies were included.
      Men were more likely than women to benefit if physical activity was part of a
      weight-loss programme. Reducing diets tended to produce more favourable weight
      loss than physical activity alone (mean weight change after 1 year from a
      reducing diet compared with an exercise programme -3.2 kg, 95% CI -4.8 kg to -1.6
      kg). The type of reducing diet did not affect long-term weight loss. A reducing
      diet plus physical activity and behaviour change gave the most effective results.
      Low-fat reducing diets, some with meal replacements, combined with physical
      activity and behaviour change training gave the most effective long-term weight
      change in men [-5.2 kg (standard error 0.2 kg) after 4 years]. Such trials may
      prevent type 2 diabetes in men and improve erectile dysfunction. Although fewer
      men joined weight-loss programmes, once recruited they were less likely to drop
      out than women (difference 11%, 95% CI 8% to 14%). The perception of having a
      health problem (e.g. being defined as obese by a health professional), the impact
      of weight loss on health problems and desire to improve personal appearance
      without looking too thin were motivators for weight loss amongst men. The key
      components differ from those found for women, with men preferring more factual
      information on how to lose weight and more emphasis on physical activity
      programmes. Interventions delivered in social settings were preferred to those
      delivered in health-care settings. Group-based programmes showed benefits by
      facilitating support for men with similar health problems, and some individual
      tailoring of advice assisted weight loss in some studies. Generally, men
      preferred interventions that were individualised, fact-based and flexible, which
      used business-like language and which included simple to understand information.
      Preferences for men-only versus mixed-sex weight-loss group programmes were
      divided. In terms of context, programmes which were cited in a sporting context
      where participants have a strong sense of affiliation showed low drop out rates
      and high satisfaction. Although some men preferred weight-loss programmes
      delivered in an NHS context, the evidence comparing NHS and commercial programmes
      for men was unclear. The effect of family and friends on participants in weight
      loss programmes was inconsistent in the evidence reviewed - benefits were shown
      in some cases, but the social role of food in maintaining relationships may also
      act as a barrier to weight loss. Evidence on the economics of managing obesity in
      men was limited and heterogeneous. LIMITATIONS: The main limitations were the
      limited quantity and quality of the evidence base and narrow outcome reporting,
      particularly for men from disadvantaged and minority groups. Few of the studies
      were undertaken in the UK. CONCLUSIONS: Weight reduction for men is best achieved
      and maintained with the combination of a reducing diet, physical activity advice
      or a physical activity programme, and behaviour change techniques. Tailoring
      interventions and settings for men may enhance effectiveness, though further
      research is needed to better understand the influence of context and content.
      Future studies should include cost-effectiveness analyses in the UK setting.
      FUNDING: This project was funded by the NIHR Health Technology Assessment
      programme.

PMID- 24857517
TI  - Thrombopoietic agents for the treatment of persistent and chronic immune
      thrombocytopenia in children.
AB  - OBJECTIVES: To determine the safety, tolerability, or efficacy of 2 licensed
      thrombopoietic agents in children with persistent and chronic immune
      thrombocytopenia (ITP). STUDY DESIGN: Retrospective analysis approved by the
      institutional review board of children with ITP not on-study who received
      thrombopoietin (TPO) therapy; 21 received romiplostim (11 at Children's Hospital
      of Orange County, 10 at Weill Cornell Medical Center) and 12 received eltrombopag
      (all at Weill Cornell Medical Center). Primary response measures were platelet
      counts >= 50 * 10(9)/L or >= 20 * 10(9)/L above baseline for 2 consecutive weeks
      and 50% of platelet counts >= 50 * 10(9)/L. Duration of treatment and adverse
      events, including bone marrow myelofibrosis (MF) consensus grades, were
      tabulated. RESULTS: Twenty-seven of 33 (82%) patients responded to TPO agents, 18
      of 21 to romiplostim, and 9 of 12 to eltrombopag, after an average of 3.6
      previous ITP therapies. These 27 patients had platelet counts >= 50 * 10(9)/L and
      >= 20 * 10(9)/L above baseline for 2 consecutive weeks; 26 had 50% of platelet
      counts >= 50 * 10(9)/L. Duration of romiplostim use ranged from 6 to 44 months
      (11/18 ongoing) and of eltrombopag 23 to 53 months (7/12 ongoing). One patient on
      eltrombopag experienced a provoked deep-vein thrombosis at site of ankle
      fracture. No other serious drug-related adverse events occurred. Among 24 bone
      marrows, 10 after greater than 2 years of therapy, 23 were normal (MF grades 0
      1); 1 was MF-2. CONCLUSION: Retrospective analysis of off-study use of TPO agents
      in children with mainly chronic ITP showed increases in platelet counts in more
      than 4 of 5 children. The long-term use of TPO agents, up to 53 months, without
      tachyphylaxis supports their efficacy. These agents appear safe, effective, and
      tolerable in children with chronic ITP.

PMID- 24857518
TI  - Plasma copeptin and therapeutic effectiveness of midodrine hydrochloride on
      postural tachycardia syndrome in children.
AB  - OBJECTIVES: Midodrine hydrochloride is used clinically to treat children with
      postural tachycardia syndrome (POTS), but it is not effective in all patients.
      This study was designed to explore the changes in plasma copeptin and its
      predictive value in assessing the therapeutic efficacy of midodrine hydrochloride
      in children with POTS. STUDY DESIGN: The study included 33 children with POTS and
      26 healthy children. The group with POTS received midodrine hydrochloride
      treatment for 1.5-3 months. The plasma copeptin was measured using a sandwich
      immunoluminometric assay. A receiver operating characteristic curve was used to
      explore the predictive value of plasma copeptin. RESULTS: The plasma copeptin in
      the group with POTS was significantly higher than that of the control group
      (10.827+/-2.459 pmol/L vs 8.845+/-1.471 pmol/L, P<.001). The plasma copeptin in
      responders to midodrine hydrochloride was significantly higher than that of
      nonresponders (12.082+/-1.998 pmol/L vs 9.646+/-2.301 pmol/L, P=.003). Receiver
      operating characteristic analysis on the predictive value of plasma copeptin
      showed that the area under the curve was 0.800 with a 95% CI of 0.640-0.959.
      Using a plasma copeptin level of 10.482 pmol/L as the cutoff point produced both
      favorite sensitivity (81.3%) and specificity (76.5%) in predicting the efficacy
      of midodrine hydrochloride therapy in children with POTS. CONCLUSIONS: Plasma
      copeptin may be considered as a predictive biomarker for the likelihood of
      successful treatment of children with POTS with midodrine hydrochloride.

PMID- 24857519
TI  - Melatonin and dopamine as biomarkers to optimize treatment in phenylketonuria:
      effects of tryptophan and tyrosine supplementation.
AB  - OBJECTIVE: To determine whether additional supplementation of tryptophan (Trp)
      and tyrosine (Tyr) improve serotonin and dopamine metabolism in individuals with
      phenylketonuria treated with large neutral amino acid (LNAA) tablets. STUDY
      DESIGN: Ten adult individuals with phenylketonuria participated in a randomized,
      double-blind, placebo-controlled cross-over study consisting of three 3-week
      phases: washout, treatment with LNAA tablets plus supplementation with either Trp
      and Tyr tablets or placebo, and LNAA tablets plus the alternate supplementation.
      An overnight protocol to measure blood melatonin, a serotonin metabolite in the
      pinealocytes, and urine 6-sulfatoxymelatonin and dopamine in first-void urine
      specimens was conducted after each phase. RESULTS: Serum melatonin and urine 6
      sulfatoxymelatonin and dopamine levels were increased in the LNAA phase (LNAA
      plus placebo) compared with the washout phase. Serum melatonin and urine 6
      sulfatoxymelatonin were not increased in the active phase (LNAA plus Trp + Tyr)
      compared with the LNAA phase, although plasma Trp:LNAA was increased compared
      with the LNAA phase. Among 7 subjects with a plasma Trp/LNAA >0.03, a negative
      correlation between urine 6-sulfatoxymelatonin and plasma phenylalanine levels
      was observed (r = -0.072). Urine dopamine levels and plasma Tyr:LNAA were
      increased in the active phase compared with the LNAA phase. CONCLUSION: Melatonin
      levels were not increased with the higher dose of Trp supplementation, but
      dopamine levels were increased with the higher dose of Tyr supplementation.
      Serotonin synthesis appears to be suppressed by high phenylalanine levels at the
      Trp hydroxylase level.

PMID- 24857520
TI  - Susceptibility-weighted imaging for calcification in Cockayne syndrome.

PMID- 24857521
TI  - Predicting hepatic steatosis in a racially and ethnically diverse cohort of
      adolescent girls.
AB  - OBJECTIVE: To develop a risk assessment model for early detection of hepatic
      steatosis using common anthropometric and metabolic markers. STUDY DESIGN: This
      was a cross-sectional study of 134 adolescent and young adult females, age 11-22
      years (mean 13.3+/-2 years) from a middle school and clinics in Madison,
      Wisconsin. The ethnic distribution was 27% Hispanic and 73% non-Hispanic; the
      racial distribution was 64% Caucasian, 31% African-American, and 5% Asian,
      Fasting glucose, fasting insulin, alanine aminotransferase (ALT), body mass index
      (BMI), waist circumference (WC), and other metabolic markers were assessed.
      Hepatic fat was quantified using magnetic resonance imaging proton density fat
      fraction (MR-PDFF). Hepatic steatosis was defined as MR-PDFF>5.5%. Outcome
      measures were sensitivity, specificity, and positive predictive value (PPV) of
      BMI, WC, ALT, fasting insulin, and ethnicity as predictors of hepatic steatosis,
      individually and combined, in a risk assessment model. Classification and
      regression tree methodology was used to construct a decision tree for predicting
      hepatic steatosis. RESULTS: MR-PDFF revealed hepatic steatosis in 16% of subjects
      (27% overweight, 3% nonoverweight). Hispanic ethnicity conferred an OR of 4.26
      (95% CI, 1.65-11.04; P=.003) for hepatic steatosis. BMI and ALT did not
      independently predict hepatic steatosis. A BMI>85% combined with ALT>65 U/L had
      9% sensitivity, 100% specificity, and 100% PPV. Lowering the ALT value to 24 U/L
      increased the sensitivity to 68%, but reduced the PPV to 47%. A risk assessment
      model incorporating fasting insulin, total cholesterol, WC, and ethnicity
      increased sensitivity to 64%, specificity to 99% and PPV to 93%. CONCLUSION: A
      risk assessment model can increase specificity, sensitivity, and PPV for
      identifying the risk of hepatic steatosis and guide the efficient use of biopsy
      or imaging for early detection and intervention.

PMID- 24857522
TI  - Probing the non-native H helix translocation in apomyoglobin folding
      intermediates.
AB  - Apomyoglobin folds via sequential helical intermediates that are formed by rapid
      collapse of the A, B, G, and H helix regions. An equilibrium molten globule with
      a similar structure is formed near pH 4. Previous studies suggested that the
      folding intermediates are kinetically trapped states in which folding is impeded
      by non-native packing of the G and H helices. Fluorescence spectra of mutant
      proteins in which cysteine residues were introduced at several positions in the G
      and H helices show differential quenching of W14 fluorescence, providing direct
      evidence of translocation of the H helix relative to helices A and G in both the
      kinetic and equilibrium intermediates. Forster resonance energy transfer
      measurements show that a 5-({2-[(acetyl)amino]ethyl}amino)naphthalene-1-sulfonic
      acid acceptor coupled to K140C (helix H) is closer to Trp14 (helix A) in the
      equilibrium molten globule than in the native state, by a distance that is
      consistent with sliding of the H helix in an N-terminal direction by
      approximately one helical turn. Formation of an S108C-L135C disulfide prevents H
      helix translocation in the equilibrium molten globule by locking the G and H
      helices into their native register. By enforcing nativelike packing of the A, G,
      and H helices, the disulfide resolves local energetic frustration and facilitates
      transient docking of the E helix region onto the hydrophobic core but has only a
      small effect on the refolding rate. The apomyoglobin folding landscape is highly
      rugged, with several energetic bottlenecks that frustrate folding; relief of any
      one of the major identified bottlenecks is insufficient to speed progression to
      the transition state.

PMID- 24857523
TI  - Respiratory infection with enterovirus genotype C117, China and Mongolia.

PMID- 24857524
TI  - Bad science, sloppy reporting, and retracted publications: should peer review be
      the scapegoat?

PMID- 24857525
TI  - Trauma-informed care: keeping mental health settings safe for veterans.
AB  - Veterans, as military personnel returning from wars in Afghanistan and Iraq, are
      frequently coping with various mental health problems. These veterans are at high
      risk for posttraumatic stress disorder (PTSD) and associated behavioral
      consequences, including self-harm, verbal and physical aggression, and violence.
      In this article, we highlight the physiological, physical, and emotional
      consequences of trauma. We focus on the unique experiences that affect veterans'
      mental health and associated behaviors and advocate for veterans to receive
      evidenced-based treatment using trauma-informed and recovery-oriented care. 

PMID- 24857526
TI  - The psychosocial impact of natural disasters among adult survivors: an
      integrative review.
AB  - The aim of this review was to identify the psychosocial impact of natural
      disasters on adult (over the age of 18 years) survivors. Databases searched
      included PsycInfo, CINAHL, Proquest, Ovid SP, Scopus, and Science Direct. The
      search was limited to articles written in English and published between 2002 and
      2012. A total of 1,642 abstracts and articles were obtained during the first
      search; 39 articles were retained. The results indicate that PTSD is the most
      studied psychosocial impact after a disaster. Mental health nurses have a
      significant role to play in supporting survivors and can assist with the
      development of resilience in community members. 

PMID- 24857527
TI  - Primary health care in the mental health workplace: insights from the Australian
      experience.
AB  - In Australia, Primary Health Care and the mental health sector have always shared
      a philosophy. In 1978, Primary Health Care was first put forward as a strategy to
      improve "health for all." Recently, the Australian Government included mental
      health as a national health priority, identifying six strategies consistent with
      a Primary Health Care approach to address the mental health of all Australians.
      Throughout this time, Primary Health Care has been highlighted in all models of
      care. However, in reality, it appears that in mental health services, mental
      health nurses, despite good intentions, are not delivering care in a planned or
      systematised way and that much needs to be done to further improve the situation
      for individuals accessing the health care system. Services currently focus on
      those identified as seriously mentally unwell; in order to really make an impact
      it is argued that services should be broader, offered to the population at large
      and, further, that the emphasis on case work at an individual level should be
      changed to an approach that considers prevention, maintenance, and follow-up as
      well as crisis intervention. This article reflects the Australian experience and
      offers some insights from that experience. 

PMID- 24857528
TI  - Depression screening on a maternity unit: a mixed-methods evaluation of nurses'
      views and implementation strategies.
AB  - Postpartum women often suffer clinically significant depressive symptoms, a
      problem addressed by nurse-delivered screening programs. In the past, success of
      these identification programs was measured in terms of screening rates; however,
      merely evaluating the screening rate does little to inform how to implement
      depression screening in clinical practice. This article describes the experiences
      of nurses in implementing depression screening on a maternity unit. We evaluate
      the practice qualitatively, by asking nurses to describe their screening
      strategies and their views about implementation, as well as quantitatively by
      assessing their screening rates and the number of women identified. Utilizing a
      framework of program evaluation, 20 maternity unit nurses completed qualitative
      assessments investigating their day-to-day experiences with this practice. To
      include the perspectives of nurses that declined to participate in qualitative
      assessments, 14 additional maternity unit nurses completed a brief survey
      assessing their views. We also assessed screening rates, defined as the number of
      women screened divided by the number eligible for screening. Maternity unit
      nurses viewed depression screening positively and were able to screen patients in
      relatively few steps, which they implemented using strategies they had developed
      themselves. Despite nurses' ongoing concern about finding time to screen, they
      achieved high screening rates and, with one exception, indicated they would opt
      to continue voluntarily. Depression screening on the maternity unit is feasible
      and embraced by attending nurses. The clinical strategies used to implement
      screening are extensively described and provide a basis for implementation in
      other settings that serve perinatal women. 

PMID- 24857529
TI  - Guided by priority: how clinicians manage access to opioid replacement therapy.
AB  - Access to opioid replacement therapy is a problem in some parts of Australia and
      it is not known how clinicians respond to this situation. The aim of this study
      is to develop a conceptual understanding of how clinicians apply clinical
      judgements in managing access to treatment. Grounded theory methodology was used
      to guide this study. Thirty-five clinicians were interviewed. The substantive
      theory presented to explain the process is Guided by Priority. By presenting this
      understanding of practice, clinicians can reflect on their actions related to the
      task and determine if they are beneficial or detrimental to consumers, which may
      influence their future practice. 

PMID- 24857530
TI  - The Aggression Observation Short Form identified episodes not reported on the
      Staff Observation Aggression Scale--Revised.
AB  - The purpose of this study is to evaluate the underreporting of violence and
      aggression on the Staff Observation Aggression Scale-Revised (SOAS-R) when
      compared to a simpler assessment: the Aggression Observation Short Form (AOS).
      During a period of one year, two open and two closed wards gathered data on both
      the SOAS-R and the AOS for all of their patients. The 22-item SOAS-R is to be
      filled out after each violent episode. The 3-item AOS is to be filled out during
      each shift and should also record the absence of violence. The SOAS-R registered
      703 incidents and the AOS registered 1,281 incidents. The agreement between the
      SOAS-R and the AOS was good (kappa = 0.65, 95% CI = 0.62-0.67). Among the 1,281
      AOS episodes, 51% were also registered on the SOAS-R. For the 176 AOS episodes
      with harm, 42% were also registered on the SOAS-R. We found 44% missing
      registrations on the AOS, primarily for open wards and for patients with short
      admission lengths. Standard instruments such as the SOAS-R underreport aggressive
      episodes by 45% or more. Underreporting can be reduced by introducing shorter
      instruments, but it cannot be completely eliminated. 

PMID- 24857531
TI  - Solving the staff's problem or meeting the patients' needs: staff members'
      reasoning about choice of action in challenging situations in psychiatric
      inpatient care.
AB  - Coercion in challenging situations is often seen as a necessary component of
      psychiatric care. This study aims to describe staff members' reasoning about
      their choice of action in challenging situations in inpatient psychiatric care.
      Focus group interviews with 26 staff members were analyzed using qualitative
      content analysis. The results provide an overview of the integrated structure of
      participants' reasoning and suggest that staff members' reasoning about choice of
      action can be described as a matter of either solving the staff's problems or
      meeting the patients' needs. These results can be of use in further research,
      educational interventions, and staff development activities. 

PMID- 24857533
TI  - The culture of research: "No I'm not gonna be no guinea pig for all of that".

PMID- 24857532
TI  - Effectiveness of resilience training versus cognitive therapy on reduction of
      depression in female Iranian college students.
AB  - Depression is the most common mental illness among women. Its prevalence in women
      is two to three times that of men. The purpose of the present study was to
      evaluate the effectiveness of resilience training on the reduction of depression
      in female college students. This semi-empirical study was carried out with two
      experimental groups and one control group. The research sample was women with
      symptoms of depression who were 18-22 years of age and living in a college
      dormitory. One experimental group was given eight 90-minute resilience training
      sessions, while the other received eight 90-minute cognitive therapy sessions.
      The control group didn't receive any interventions. The three groups under study
      were evaluated using the Beck II depression inventory before and after the
      interventions and two months after the treatment had ended. The three groups
      didn't have significant differences in age, marital status, or depression scores
      on the pretest. The resilience training group and cognitive therapy group showed
      a significant decrease in the average depression score from pretest to posttest
      and from pretest to follow-up. The main effect of groups, stage, and interaction
      between groups and stage also were significant (all were p < 0.001). There was no
      significant difference between effectiveness of resilience training and cognitive
      therapy on depression but there was a significant difference between these two
      treatment groups and the control group. The effectiveness of resilience training
      was just as good as the effectiveness of cognitive therapy. The effects of
      resilience training on depression remained stable from the posttest to the follow
      up, like that of cognitive therapy. 

PMID- 24857534
TI  - Therapeutic boundaries or barriers: thoughts on emotional distance in psychiatric
      mental-health nursing.

PMID- 24857535
TI  - [Response of Lina Tibi, Nicolas Clauss, Elise Enderlin, Fabrice Hubele, Izzie
      Jacques Namer, and Carole Mathelin to the article by M. Bailly et al. ].

PMID- 24857536
TI  - [Contraception's choice: women's opinion, satisfaction and profile. Results of a
      French national survey of a representative sample of 5963 women].
AB  - OBJECTIVES: To describe French women's use of contraceptive methods and study
      their satisfaction and expectations about contraception. PATIENTS AND METHODS: A
      survey carried out by mail questionnaire filled in by a representative sample
      group of French women aged 15 to 45 years (Panel Postal Metascope TNS Sofres) in
      June 2007. RESULTS: Of 10,000 questionnaires sent out, 6044 questionnaires were
      returned, of which 5963 were usable. Seventy-three percent of women surveyed used
      some method of contraception, of which 46% was an oral contraceptive, 15% an IUD
      and 7% used condoms. A minority used new contraceptive methods (implant, patch,
      vaginal ring). The average age at first sexual relationship was 17.8 years. It
      was 18.5 among 40-45-year-olds and gradually reduced to 16.7 in the under 25-year
      olds. Twenty-three percent of pregnancies remain unwanted and unplanned. For 96%
      of patients, the choice of contraception was considered to be important. Thirty
      six percent thought that contraception could be harmful to health. Only 63% of
      women believed themselves to be well informed the first time they used
      contraception. Satisfaction for contraception method was evaluated from 7.3/10
      (condom) to 9.7/10 (sterilization). DISCUSSION AND CONCLUSION: Twenty-seven
      percent of women do not use any contraception and 23% of pregnancies are unwanted
      despite a large offering of contraceptives. Our study enables the drawing of
      'patient-profiles' for the main methods of contraception in order to better
      determine women's expectations and to pass the findings on to health
      professionals.

PMID- 24857537
TI  - Molecular biology of calcific aortic valve disease: towards new pharmacological
      therapies.
AB  - Calcific aortic valve disease (CAVD) is a chronic process leading to fibrosis and
      mineralization of the aortic valve. Investigations in the last several years have
      emphasized that key underlying molecular processes are involved in the
      pathogenesis of CAVD. In this regard, the processing of lipids and their
      retention has been underlined as an important mechanism that triggers
      inflammation. In turn, inflammation promotes/enhances the mineralization of valve
      interstitial cells, the main cellular component of the aortic valve. On the other
      hand, transformation of valve interstitial cells into myofibroblasts and
      osteoblast-like cells is determined by several signaling pathways having
      reciprocal cross-talks. In addition, the mineralization of the aortic valve has
      been shown to rely on ectonucleotidase and purinergic signaling. In this review,
      the authors have highlighted key molecular underpinnings of CAVD that may have
      significant relevance for the development of novel pharmaceutical therapies. 

PMID- 24857538
TI  - Metformin use and prostate cancer risk.
AB  - BACKGROUND: Metformin may decrease prostate cancer (PCa) risk by reducing
      hyperinsulinemia-associated carcinogenesis or through direct effects on cancer
      cells. OBJECTIVE: To evaluate the association between metformin use and PCa
      diagnosis. DESIGN, SETTING, AND PARTICIPANTS: We used the Danish Cancer Registry
      and the Aarhus University Prescription Database to conduct a nested case-control
      study among men residing in northern Denmark from 1989 to 2011. We identified 12
      226 cases of PCa and used risk-set sampling to select 10 population controls per
      case (n=122,260) from among men alive on the index date and born in the same
      year. A sensitivity analysis was conducted using subjects who had prostate
      specific antigen (PSA) testing prior to 1 yr before the index date. INTERVENTION:
      Metformin exposure was assessed using prescriptions redeemed before the index
      date. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Odds ratios (ORs) and 95%
      confidence intervals (CIs) were calculated using logistic regression. The
      association between metformin use and PCa diagnosis was determined, controlling
      for diabetes severity and other potential confounders. RESULTS AND LIMITATIONS:
      Metformin users were at decreased risk of PCa diagnosis compared with never-users
      (adjusted OR [aOR]: 0.84; 95% CI, 0.74-0.96). Diabetics on no medication (aOR:
      0.98; 95% CI, 0.89-1.09) or on other oral hypoglycemics (aOR: 0.98; 95% CI, 0.86
      1.10) did not have a reduced risk of PCa, while users of insulin did have a
      reduced risk (aOR: 0.77; 95% CI, 0.64-0.93). In the PSA-tested group, metformin
      use was associated with decreased risk of PCa compared with nonuse (aOR: 0.66;
      95% CI, 0.51-0.86). Diabetics on no medication (aOR: 1.03; 95% CI, 0.86-1.24),
      diabetics on other oral hypoglycemics (aOR: 0.92; 95% CI, 0.70-1.20), and insulin
      users (aOR: 0.83; 95% CI, 0.56-1.24) did not have a statistically significant
      reduced risk of cancer. CONCLUSIONS: Metformin use was associated with decreased
      risk of PCa diagnosis, whereas diabetics using other oral hypoglycemics had no
      decreased risk. PATIENT SUMMARY: We studied the relationship between metformin (a
      diabetic medication) and prostate cancer in Denmark. We found that metformin
      reduced the risk of prostate cancer diagnosis, whereas other oral antidiabetic
      medications did not.

PMID- 24857539
TI  - Technique and outcomes of robot-assisted retroperitoneoscopic partial
      nephrectomy: a multicenter study.
AB  - BACKGROUND: Robot-assisted retroperitoneoscopic partial nephrectomy (RARPN) may
      be used for posterior renal masses or with prior abdominal surgery; however,
      there is relatively less familiarity with RARPN. OBJECTIVE: To demonstrate RARPN
      technique and outcomes. DESIGN, SETTING, AND PARTICIPANTS: A retrospective
      multicenter study of 227 consecutive RARPNs was performed at the Swedish Medical
      Center, the University of Michigan, and the University of California, Los
      Angeles, from 2006 to 2013. SURGICAL PROCEDURE: RARPN. OUTCOME MEASUREMENTS AND
      STATISTICAL ANALYSIS: We assessed positive margins and cancer recurrence.
      Stepwise regression was used to examine factors associated with complications,
      estimated blood loss (EBL), warm ischemia time (WIT), operative time (OT), and
      length of stay (LOS). RESULTS AND LIMITATIONS: The median age was 60 yr
      (interquartile range [IQR]: 52-66), and the median body mass index (BMI) was 28.2
      kg/m(2) (IQR: 25.6-32.6). Median maximum tumor diameter was 2.3 cm (IQR: 1.7
      3.1). Median OT and WIT were 165 min (IQR: 134-200) and 19 min (IQR: 16-24),
      respectively; median EBL was 75 ml (IQR: 50-150), and median LOS was 2 d (IQR: 1
      3). Twenty-eight subjects (12.3%) experienced complications, three (1.3%) had
      urine leaks, and three (1.3%) had pseudoaneurysms that required reintervention.
      There was one conversion to radical nephrectomy and three transfusions. Overall,
      143 clear cell carcinomas (62.6%) composed most of the histology with eight
      positive margins (3.5%) and two recurrences (0.9%) with a median follow-up of 2.7
      yr. In adjusted analyses, intersurgeon variation was associated with
      complications (odds ratio [OR]: 3.66; 95% confidence interval, 1.31-10.27; p =
      0.014) and WIT (parameter estimate [PE; plus or minus standard error]: 4.84 +/-
      2.14; p = 0.025). Higher surgeon volume was associated with shorter WIT (PE: 
      0.06 +/- 0.02; p = 0.002). Higher BMI was associated with longer OT (PE: 2.09 +/-
      0.56; p < 0.001). Longer OT was associated with longer LOS (PE: 0.01 +/- 0.01; p
      = 0.002). Finally, there was a trend for intersurgeon variation in OT (PE: 18.5
      +/- 10.3; p = 0.075). CONCLUSIONS: RARPN has acceptable morbidity and oncologic
      outcomes, despite intersurgeon variation in WIT and complications. Greater
      experience is associated with shorter WIT. PATIENT SUMMARY: Robot-assisted
      retroperitoneoscopic partial nephrectomy has acceptable morbidity and oncologic
      outcomes, and there is intersurgeon variation in warm ischemia time and
      complications.

PMID- 24857540
TI  - Hepcidin expression in liver cells: evaluation of mRNA levels and transcriptional
      regulation.
AB  - Hepcidin produced in the liver negatively regulates intestinal iron absorption,
      and the bone morphogenetic protein (BMP) pathway is well-known to stimulate
      hepcidin expression. However, the regulation of hepcidin expression has not been
      fully elucidated. In this study, we evaluate different systems that can be used
      to determine how hepcidin expression is regulated. The basal expression of
      hepcidin in liver cell lines, such as HepG2 cells and Hepa1-6 cells, was lower
      than that in the liver and primary hepatocytes; the expression levels of hepcidin
      in the cell lines were near the limit of detection for RT-PCR and RT-qPCR
      analyses. Treatment with trichostatin A, RNAlater, or MG-132 enhanced the
      expression of hepcidin in HepG2 cells, suggesting that histone deacetylation,
      instability of mRNA, or proteosomal degradation of the protein(s) that positively
      regulate hepcidin expression may be responsible for the decreased expression of
      hepcidin in HepG2 cells. In luciferase-based reporter assays, BMP induced the
      transcription of a reporter, hepcidin(-2018)-luc, that contains nt -2018 through
      nt -35 of the hepcidin promoter in HepG2 cells and Hepa1-6 cells. However, BRE
      luc, a representative reporter used to evaluate BMP signaling, was unresponsive
      to BMP in HepG2 cells. These results suggest that hepcidin transcription can be
      best evaluated in liver cell lines and that the hepcidin promoter senses BMP
      signaling with high sensitivity. The present study demonstrates that studies
      regarding the regulation of hepcidin expression at the mRNA level should be
      evaluated in primary hepatocytes, and liver cell lines are well-suited for
      studies examining the transcriptional regulation of hepcidin.

PMID- 24857541
TI  - Dysmotility by mechanical bowel preparation using polyethylene glycol.
AB  - BACKGROUND: The effects of mechanical bowel preparation (MBP) on morbidity (e.g.,
      anastomotic leakage and surgical site infection) have been evaluated. Its effect
      on early recovery after surgery has drawn renewed attention, and its use is
      discouraged in the postsurgical management of enhanced recovery. However, most
      surgeons in Japan prefer polyethylene glycol (PEG) for MBP. We investigated the
      effect of MBP with PEG on postoperative intestinal motility. MATERIALS AND
      METHODS: We prospectively evaluated a consecutive series of 258 colon cancer
      patients who underwent colonic resection and primary anastomosis. We orally
      administered 2000 mL of PEG in the PEG group and did not administer PEG to
      patients in the no-PEG group. Postoperative gastrointestinal motility was
      assessed with radiopaque markers. All patients ingested radiopaque markers 2 h
      before surgery. Postoperative intestinal motility was radiologically assessed by
      counting the number of residual markers. Abdominal radiography was conducted on
      postoperative days 1, 3, and 5 to count residual markers in the large and small
      intestines. RESULTS: The total number of residual markers in the no-PEG group was
      less than that in the PEG group on day 5 (P < 0.01) but not on days 1 and 3. On
      all 3 d, the numbers of residual markers in the small intestine were
      significantly less in the no-PEG group than in the PEG group (P < 0.001). There
      were no differences in postoperative complications between the no-PEG and PEG
      groups. CONCLUSIONS: PEG can negatively affect postoperative intestinal motility,
      and MBP using PEG is unnecessary in elective colon cancer surgery.

PMID- 24857542
TI  - Synthesis, cytotoxicity against human oral cancer KB cells and structure-activity
      relationship studies of trienone analogues of curcuminoids.
AB  - A general method for the synthesis of substituted (1E,4E,6E)-1,7-diphenylhepta
      1,4,6-trien-3-ones, based on the aldol condensations of substituted 4-phenylbut-3
      en-2-ones and substituted 3-phenylacrylaldehydes, was achieved. The natural
      trienones 4 and 5 have been synthesized by this method, together with the
      trienone analogues 9-20. These analogues were evaluated for their cytotoxic
      activity against human oral cancer KB cell line. The structure-activity
      relationship study has indicated that the analogues with the 1,4,6-trien-3-one
      function are more potent than the curcuminoid-type function. Analogues with meta
      oxygen function on the aromatic rings are more potent than those in the ortho-
      and para-positions. Free phenolic hydroxy group is more potent than the
      corresponding methyl ether analogues. Among the potent trienones, compounds 11,
      18 and 20 were more active than the anticancer drug ellipticine. All compounds
      were also evaluated against the non-cancerous Vero cells and it was found that
      compounds 11, 12 and 17 were much less toxic than curcumin (1); they showed high
      selectivity indices of 35.46, 33.46 and 31.68, respectively. These analogues are
      regarded as the potent trienones for anti-oral cancer study. 

PMID- 24857543
TI  - Gramicidin D enhances the antibacterial activity of fluoride.
AB  - Fluoride is a toxic anion found in many natural environments. One of the major
      bacterial defenses against fluoride is the cell envelope, which limits passage of
      the membrane-impermeant fluoride anion. Accordingly, compounds that enhance the
      permeability of bacterial membranes to fluoride should also enhance fluoride
      toxicity. In this study, we demonstrate that the pore-forming antibiotic
      gramicidin D increases fluoride uptake in Bacillus subtilis and that the
      antibacterial activity of this compound is potentiated by fluoride. Polymyxin B,
      another membrane-targeting antibiotic with a different mechanism of action, shows
      no such improvement. These results, along with previous findings, indicate that
      certain compounds that destabilize bacterial cell envelopes can enhance the
      toxicity of fluoride. 

PMID- 24857544
TI  - [Reconstruction of an extensive endonasal chondromucosal defect with a composite
      graft].
AB  - INTRODUCTION: Reconstruction of an endonasal chondromucosal defect without skin
      defect is a rare event, which involves functional and esthetic outcomes. We
      report the original use of a composite graft, for the repair of an endonasal
      chondromucosal defect. OBSERVATION: A 57-year-old woman presented with extensive
      tissue loss after the complete resection of an arteriovenous malformation. The
      excision procedure removed a cartilaginous part of the dome, the lateral crus of
      the alar cartilage, and the adjacent mucosa. An auricular composite graft allowed
      for an effective reconstruction, with a very satisfactory result, in a single
      surgical step. DISCUSSION: Using an endonasal composite graft has rarely been
      reported even though there are few alternatives for the reconstruction of an
      endonasal chondromucosal defect.

PMID- 24857545
TI  - Mesoporous amorphous FePO4 nanospheres as high-performance cathode material for
      sodium-ion batteries.
AB  - FePO4 nanospheres are synthesized successfully through a simple chemically
      induced precipitation method. The nanospheres present a mesoporous amorphous
      structure. Electrochemical experiments show that the FePO4/C electrode
      demonstrates a high initial discharging capacity of 151 mAh g(-1) at 20 mA g(-1),
      stable cyclablilty (94% capacity retention ratio over 160 cycles), as well as
      high rate capability (44 mAh g(-1) at 1000 mA g(-1)) for Na-ion storage. The
      superior electrochemical performance of the FePO4/C nanocomposite is due to its
      particular mesoporous amorphous structure and close contact with the carbon
      framework, which significantly improve the ionic and electronic transport and
      intercalation kinetics of Na ions. 

PMID- 24857546
TI  - beta-lactoglobulin as a vector for beta-carotene food fortification.
AB  - Food fortification is a strategy to overcome vitamin A deficiency in developing
      countries. Our aim was to investigate the involvement of the bovine milk protein
      beta-lactoglobulin (beta-Lg), a potential retinoid carrier, in vitamin A
      absorption. In vivo experiments were conducted by force-feeding mice with retinol
      or beta-carotene associated with either beta-Lg or oil-in-water emulsion, with
      subsequent determination of both vitamin A intestinal mucosa and plasma contents.
      Caco-2 cells were then used to investigate the mechanisms of vitamin A uptake
      when delivered by either beta-Lg or mixed micelles. We showed that beta-Lg was as
      efficient as emulsion to promote beta-carotene, but not retinol, absorption in
      mice. Similar results were obtained in vitro. Interestingly, an inhibitor of the
      Scavenger Receptor Class B Type I significantly decreased the uptake of micellar
      beta-carotene but not that of beta-carotene bound to beta-Lg. Overall, we showed
      that beta-Lg would be a good vector for beta-carotene food fortification. 

PMID- 24857547
TI  - O-GlcNAcylation regulates cancer metabolism and survival stress signaling via
      regulation of the HIF-1 pathway.
AB  - The hexosamine biosynthetic pathway elevates posttranslational addition of O
      linked beta-N-acetylglucosamine (O-GlcNAc) on intracellular proteins. Cancer
      cells elevate total O-GlcNAcylation by increasing O-GlcNAc transferase (OGT)
      and/or decreasing O-GlcNAcase (OGA) levels. Reducing O-GlcNAcylation inhibits
      oncogenesis. Here, we demonstrate that O-GlcNAcylation regulates glycolysis in
      cancer cells via hypoxia-inducible factor 1 (HIF-1alpha) and its transcriptional
      target GLUT1. Reducing O-GlcNAcylation increases alpha-ketoglutarate, HIF-1
      hydroxylation, and interaction with von Hippel-Lindau protein (pVHL), resulting
      in HIF-1alpha degradation. Reducing O-GlcNAcylation in cancer cells results in
      activation of endoplasmic reticulum (ER) stress and cancer cell apoptosis
      mediated through C/EBP homologous protein (CHOP). HIF-1alpha and GLUT1 are
      critical for OGT-mediated regulation of metabolic stress, as overexpression of
      stable HIF-1 or GLUT1 rescues metabolic defects. Human breast cancers with high
      levels of HIF-1alpha contain elevated OGT, and lower OGA levels correlate
      independently with poor patient outcome. Thus, O-GlcNAcylation regulates cancer
      cell metabolic reprograming and survival stress signaling via regulation of HIF
      1alpha.

PMID- 24857548
TI  - Gain-of-function mutant p53 promotes cell growth and cancer cell metabolism via
      inhibition of AMPK activation.
AB  - Many mutant p53 proteins (mutp53s) exert oncogenic gain-of-function (GOF)
      properties, but the mechanisms mediating these functions remain poorly defined.
      We show here that GOF mutp53s inhibit AMP-activated protein kinase (AMPK)
      signaling in head and neck cancer cells. Conversely, downregulation of GOF
      mutp53s enhances AMPK activation under energy stress, decreasing the activity of
      the anabolic factors acetyl-CoA carboxylase and ribosomal protein S6 and
      inhibiting aerobic glycolytic potential and invasive cell growth. Under
      conditions of energy stress, GOF mutp53s, but not wild-type p53, preferentially
      bind to the AMPKalpha subunit and inhibit AMPK activation. Given the importance
      of AMPK as an energy sensor and tumor suppressor that inhibits anabolic
      metabolism, our findings reveal that direct inhibition of AMPK activation is an
      important mechanism through which mutp53s can gain oncogenic function.

PMID- 24857549
TI  - LincRNA-p21 activates p21 in cis to promote Polycomb target gene expression and
      to enforce the G1/S checkpoint.
AB  - The p53-regulated long noncoding RNA lincRNA-p21 has been proposed to act in
      trans via several mechanisms ranging from repressing genes in the p53
      transcriptional network to regulating mRNA translation and protein stability. To
      further examine lincRNA-p21 function, we generated a conditional knockout mouse
      model. We find that lincRNA-p21 predominantly functions in cis to activate
      expression of its neighboring gene, p21. Mechanistically, we show that lincRNA
      p21 acts in concert with hnRNP-K as a coactivator for p53-dependent p21
      transcription. Additional phenotypes of lincRNA-p21 deficiency could be
      attributed to diminished p21 levels, including deregulated expression and altered
      chromatin state of some Polycomb target genes, a defective G1/S checkpoint,
      increased proliferation rates, and enhanced reprogramming efficiency. These
      findings indicate that lincRNA-p21 affects global gene expression and influences
      the p53 tumor suppressor pathway by acting in cis as a locus-restricted
      coactivator for p53-mediated p21 expression.

PMID- 24857552
TI  - Marital quality and self-efficacy: influence on disease management among
      individuals with rheumatoid arthritis.
AB  - Individuals with rheumatoid arthritis (RA) struggle to maintain improved
      functional ability and reduced pain levels. Health education emphasizing self
      efficacy helps individuals to adjust with the disease outcome and progression. As
      a basis to develop comprehensive evidence-based patient education programs, the
      aim of the study was to examine the role of marriage as a predictor of pain and
      functional self-efficacy among individuals with RA. Review of the regression
      analysis did not provide support for the relationships between marital quality
      and self-efficacy. Relationships were not observed between marital quality,
      length of marriage, and self-efficacy as predicted by the first hypothesis.
      Additional regression analysis examination found that marital quality, length of
      marriage, pain, and health assessment together reported significant variance in
      self-efficacy. However, only health assessment significantly predicted self
      efficacy. Other nonexamined variables could have influenced the independent
      marital quality effects. Future longitudinal studies with larger sample sizes can
      further validate the current findings. 

PMID- 24857550
TI  - Unambiguous identification of miRNA:target site interactions by different types
      of ligation reactions.
AB  - To exert regulatory function, miRNAs guide Argonaute (AGO) proteins to partially
      complementary sites on target RNAs. Crosslinking and immunoprecipitation (CLIP)
      assays are state-of-the-art to map AGO binding sites, but assigning the targeting
      miRNA to these sites relies on bioinformatics predictions and is therefore
      indirect. To directly and unambiguously identify miRNA:target site interactions,
      we modified our CLIP methodology in C. elegans to experimentally ligate miRNAs to
      their target sites. Unexpectedly, ligation reactions also occurred in the absence
      of the exogenous ligase. Our in vivo data set and reanalysis of published
      mammalian AGO-CLIP data for miRNA-chimeras yielded ~17,000 miRNA:target site
      interactions. Analysis of interactions and extensive experimental validation of
      chimera-discovered targets of viral miRNAs suggest that our strategy identifies
      canonical, noncanonical, and nonconserved miRNA:targets. About 80% of miRNA
      interactions have perfect or partial seed complementarity. In summary, analysis
      of miRNA:target chimeras enables the systematic, context-specific, in vivo
      discovery of miRNA binding.

PMID- 24857551
TI  - PP2A-mediated regulation of Ras signaling in G2 is essential for stable
      quiescence and normal G1 length.
AB  - Quiescence (G0) allows cycling cells to reversibly cease proliferation. A
      decision to enter quiescence is suspected of occurring early in G1, before the
      restriction point (R). Surprisingly, we have identified G2 as an interval during
      which inhibition of the protein phosphatase PP2A results in failure to exhibit
      stable quiescence. This effect is accompanied by shortening of the ensuing G1.
      The PP2A subcomplex required for stable G0 contains the B56gamma B subunit. After
      PP2A inhibition in G2, aberrant overexpression of cyclin E occurs during mitosis
      and is responsible for overriding quiescence. Strikingly, suppression of Ras
      signaling re-establishes normal cyclin E levels during M and restores G0. These
      data point to PP2A-B56gamma-driven Ras signaling modulation in G2 as essential
      for suppressing aberrant cyclin E expression during mitosis and thereby achieving
      normal G0 control. Thus, G2 is an interval during which the length and growth
      factor dependence of the next G1 interval are established. 

PMID- 24857553
TI  - Social work and medical care: electronic reminders to address adherence.
AB  - Social workers are often involved with patients and families around adherence,
      both to clinic appointments as well as to the medication regimen. An evidence
      based practice project was created and implemented to determine the efficacy of
      electronic reminders such as text messaging on adherence. The implications of
      improving adherence can positively impact the patient on an individual level as
      well as reduce costs and increase revenue at a systems level. 

PMID- 24857554
TI  - Intergenerational families of holocaust survivors: designing and piloting a
      family resilience template.
AB  - Researchers from the Templeton study, "Forgiveness, Resiliency, and Survivorship
      Among Holocaust Survivors," and the Transcending Trauma Project, combined efforts
      to examine six transcripts of interviews with survivors of the Nazi Holocaust.
      The researchers focused on the nature of parent-child family dynamics before,
      during, and after the Holocaust. They refined a Family Resilience Template (FRT)
      originally based on an ecological-systems design, adding an attachment theory
      component and a quantitative methodology. The goal of the research project was to
      pilot the FRT by further defining terms and adding a Quality of Family Dynamics
      Paradigm to encompass an intergenerational dimension. The researchers arrived at
      a consensus of item definitions, establishing the initial face validity of the
      FRT. 

PMID- 24857555
TI  - Science, pseudoscience, and the frontline practitioner: the vaccination/autism
      debate.
AB  - This article demonstrates how misinformation concerning autism and vaccinations
      was created and suggests that social workers may be perfectly poised to challenge
      pseudoscience interpretations. Utilizing social network theory, this article
      illustrates how erroneous research, mass media, and public opinion led to a
      decreased use of vaccinations in the United States and a seven-fold increase in
      measles outbreaks. It traces the dissemination of spurious research results and
      demonstrates how information was transmitted via a system of social network nodes
      and community ties. This article encourages social workers, as frontline
      knowledge brokers, to counter misinformation, which may lead to significant
      public health consequences. 

PMID- 24857556
TI  - Health care access, utilization, and problems in a sample of former foster
      children: a longitudinal investigation.
AB  - Three years of descriptive data that describe health problems and access to care
      for former foster youth are presented (n = 92). Findings were that most youths
      had health coverage at emancipation, but the proportion with coverage shrinks
      after three years to 57%. Youths generally reported good health despite the loss
      of Medicaid and increasing difficulties with access to care. However, mental
      health problems and substance abuse problems in the sample remained high over the
      three years of study. Most of the mental health and substance abuse problems
      remained untreated. The policy implications of findings are discussed. 

PMID- 24857557
TI  - Motivational interviewing at the intersections of depression and intimate partner
      violence among African American women.
AB  - This article focuses on design, training, and delivery of a culturally tailored,
      multi-faceted intervention that used motivational interviewing (MI) and case
      management to reduce depression severity among African American survivors of
      intimate partner violence (IPV). We present the details of the intervention and
      discuss its implementation as a means of creating and providing culturally
      appropriate depression and violence services to African American women. We used a
      community-based participatory research approach to develop and evaluate the multi
      faceted intervention. As part of the evaluation, we collected process measures
      about the use of MI, assessed MI fidelity, and interviewed participants about
      their experiences with the program. 

PMID- 24857559
TI  - Reframing professional boundaries in healthcare: a systematic review of
      facilitators and barriers to task reallocation from the domain of medicine to the
      nursing domain.
AB  - AIM: To explore the main facilitators and barriers to task reallocation.
      BACKGROUND: One of the innovative approaches to dealing with the anticipated
      shortage of physicians is to reallocate tasks from the professional domain of
      medicine to the nursing domain. Various (cost-)effectiveness studies demonstrate
      that nurse practitioners can deliver as high quality care as physicians and can
      achieve as good outcomes. However, these studies do not examine what factors may
      facilitate or hinder such task reallocation. METHOD: A systematic literature
      review of PubMed and Web of Knowledge supplemented with a snowball research
      method. The principles of thematic analysis were followed. RESULTS: The 13
      identified relevant papers address a broad spectrum of task reallocation
      (delegation, substitution and complementary care). Thematic analysis revealed
      four categories of facilitators and barriers: (1) knowledge and capabilities, (2)
      professional boundaries, (3) organisational environment, and (4) institutional
      environment. CONCLUSION: Introducing nurse practitioners in healthcare requires
      organisational redesign and the reframing of professional boundaries. Especially
      the facilitators and barriers in the analytical themes of 'professional
      boundaries' and 'organisational environment' should be considered when
      reallocating tasks. If not, these factors might hamper the cost-effectiveness of
      task reallocation in practice.

PMID- 24857560
TI  - Effect of gravity on colloid transport through water-saturated columns packed
      with glass beads: modeling and experiments.
AB  - The role of gravitational force on colloid transport in water-saturated columns
      packed with glass beads was investigated. Transport experiments were performed
      with colloids (clays: kaolinite KGa-1b, montmorillonite STx-1b). The packed
      columns were placed in various orientations (horizontal, vertical, and diagonal)
      and a steady flow rate of Q = 1.5 mL/min was applied in both up-flow and down
      flow modes. All experiments were conducted under electrostatically unfavorable
      conditions. The experimental data were fitted with a newly developed, analytical,
      one-dimensional, colloid transport model. The effect of gravity is incorporated
      in the mathematical model by combining the interstitial velocity (advection) with
      the settling velocity (gravity effect). The results revealed that flow direction
      influences colloid transport in porous media. The rate of particle deposition was
      shown to be greater for up-flow than for down-flow direction, suggesting that
      gravity was a significant driving force for colloid deposition. 

PMID- 24857561
TI  - A robust probe for lighting up intracellular telomerase via primer extension to
      open a nicked molecular beacon.
AB  - A nicked molecular beacon (MB)-functionalized probe has been designed for in situ
      imaging and detection of intracellular telomerase activity. The nick separates
      the MB into two segments: a shorter telomerase primer (TSP) sequence as a part of
      the 5'-end stem and a longer sequence to form a loop with one thiol-labeled 3'
      end stem. The MB can be opened by substitutional hybridization of the telomerase
      triggered stem elongation product, which leads to separation of the Cy5 at the 5'
      end nick from the gold nanoparticle (AuNP) as the nanocarrier and thus inhibits
      the energy transfer from Cy5 to AuNP. Upon endocytosis of the probe, the TSP can
      be extended by intracellular telomerase at its 3' end to produce the telomeric
      repeated sequence, which leads to the inner chain substitution and thus turns on
      the fluorescence of Cy5. The probe provides a one-step incubation technique for
      quantification and monitoring of the telomerase activity in living cells. The
      practicality of the proposed approach for distinguishing tumor cells from normal
      cells and monitoring the decrease of telomerase activity during treatment with
      antitumor drugs demonstrates its potential in clinical diagnostic and therapeutic
      monitoring. 

PMID- 24857562
TI  - Morphometric analysis and anatomical variations of infraorbital foramen: a study
      in adult North Indian population.
AB  - PURPOSE: Various studies have been conducted on morphometric variations of
      infraorbital foramen to provide data to surgeons for nerve block in infraorbital
      region. This study aims to analyse the anatomical variations by comparing various
      morphometric measurements of infraorbital foramen in dry skulls of adult North
      Indian population. This study becomes relevant in the present study group as very
      scant data is available about the variations and morphometric measurements in
      Indian population. The data thus collected can be standardized and become useful
      for the surgeons working in this area of face. MATERIALS AND METHODS: The study
      was conducted on 75 dry adult human skulls, which were a part of Department of
      Anatomy, used for teaching purposes in medical colleges. Straight distance of the
      Infraorbital foramen from the infraorbital rim, supraorbital foramen and sagittal
      plane was measured. The position of the infraorbital foramen was determined in
      relation to maxillary teeth and supraorbital foramen. The data thus obtained was
      analysed. RESULTS: The distance of infraorbital foramen from infraorbital rim,
      supraorbital foramen, sagittal plane in the present study was found to be 6.71 +/
      1.11 mm, 42.02 +/- 4.31 mm and 31.94 +/- 4.88 mm respectively. The position of
      infraorbital foramen was lateral in relation to supraorbital foramen (in 88% of
      cases). Infraorbital foramen was above the 1st premolar tooth in most of the
      cases. Accessory infraorbital foramen was found in 11.2% cases (double foramen).
      CONCLUSION: The data thus obtained will perhaps be helpful to the surgeons in
      identifying the extent of the operative field thereby reducing procedural risks.

PMID- 24857563
TI  - The effect of talking about psychological trauma with a significant other on
      heart rate reactivity in individuals with posttraumatic stress disorder.
AB  - Individuals with posttraumatic stress disorder (PTSD) commonly make efforts to
      avoid trauma-oriented conversations with their significant others, which may
      interfere with the natural recovery process. Trauma-oriented conversations can be
      experienced as physiologically arousing, depending on the intensity of PTSD
      symptoms and perceptions of social support. In the current investigation, changes
      in heart rate responses to a trauma-oriented social interaction with a
      significant other were assessed. Perceived supportive and unsupportive or
      negative social interactions were examined as moderators of the association
      between heart rate changes to this context and intensity of PTSD symptoms. A
      total of 46 individuals with PTSD completed diagnostic interviews and self-report
      measures of symptoms and perceived supportive and negative social interactions
      during a trauma-oriented social interaction with a significant other. Heart rate
      was continuously measured during this interaction. Results showed that engagement
      in a trauma-oriented social interaction was predictive of elevations in heart
      rate that positively correlated with intensity of PTSD symptoms. The moderation
      hypothesis was partially supported. In addition, perceived negative social
      interactions positively correlated with elevations in heart rate. These findings
      can inform social intervention efforts for individuals with PTSD. 

PMID- 24857564
TI  - Distinct profiles of behavioral inhibition and activation system sensitivity in
      unipolar vs. bipolar mood disorders.
AB  - Psychiatric outpatients with mood disorders (n=275) and community controls
      (n=733) completed a measure of Behavioral Inhibition System (BIS) and Behavioral
      Activation System (BAS) sensitivity; psychiatric outpatients also completed
      measures of mood symptom severity. All patients scored higher on BIS compared to
      controls; patients with bipolar disorders scored higher on BAS scales compared to
      patients with depressive disorders. BIS and BAS demonstrated unique patterns of
      association with mood symptoms. Results support the clinical utility of the
      BIS/BAS. 

PMID- 24857565
TI  - Harm avoidance moderates the relationship between internalized stigma and
      depressive symptoms in patients with schizophrenia.
AB  - This study investigated the associations between internalized stigma, depressive
      symptoms, and temperament dimension Harm avoidance. One hundred and seventeen
      stable outpatients with schizophrenia completed a battery of self-report
      instruments. Internalized stigma was significantly positively related to
      depressive symptoms, while Harm avoidance moderated the internalized stigma
      depressive symptoms relationship. 

PMID- 24857566
TI  - Quality of life in eating disorders: a meta-analysis.
AB  - Eating disorders (EDs) comprise a variety of symptoms and have a profound impact
      on everyday life. They are associated with high morbidity and mortality. The
      objective of this study was to analyse published data on health-related quality
      of life (HRQoL) in EDs so as to compare the results to general population norm
      data and to investigate potential differences between ED diagnostic groups. A
      systematic review of the current literature was conducted using a keyword-based
      search in PubMed and PsychInfo. The search covered anorexia nervosa (AN), bulimia
      nervosa (BN), eating disorders not otherwise specified (EDNOS) and binge eating
      disorder (BED) and used the Medical Outcomes Study Short Form-36 Health Survey
      (SF-36) as a measure of HRQoL. Of the 102 citations identified, 85 abstracts were
      reviewed and seven studies were included in the meta-analysis. AN patients were
      included in five studies (n=227), BN in four studies (n=216), EDNOS in two
      studies (n=166) and BED in four studies (n=148). We tested for between-study
      variation and significant differences between the diagnostic groups. The results
      confirmed a significantly lower level of HRQoL in all EDs compared to a
      population mean. It was not possible to establish any differences between the
      diagnostic groups. 

PMID- 24857567
TI  - Microfluidic platform for direct capture and analysis of airborne Mycobacterium
      tuberculosis.
AB  - Airborne Mycobacterium tuberculosis is the main source of tuberculosis infection,
      which is known as one of the worldwide infectious diseases. Direct capture and
      analysis of airborne Mycobacterium tuberculosis is essential for disease
      prevention and control. At present, low concentration of pathogens directly
      collected from the air is the major drawback for rapid analysis. Herein an
      integrated microfluidic system capable of airborne Mycobacterium tuberculosis
      capture, enrichment, and rapid bacteriological immunoassay was developed. The
      whole detection time was decreased to less than 50 min including 20 min of
      enrichment and 30 min of immunoreaction analysis. It had the advantages of low
      detection limit, fast detection speed, and low reagent consumption compared with
      conventional techniques, showing the potential to become a new airborne pathogen
      analysis platform. 

PMID- 24857572
TI  - Evaluation of thyroid incidentaloma.
AB  - Thyroid nodules are an extremely common endocrine disorder with a generally
      accepted prevalence of around 4% to 7%. Incidental thyroid nodules are typically
      nonpalpable thyroid nodules found during radiographic evaluation for a non
      thyroid-related issue (eg, computed tomographic scan, positron emission
      tomography scan, carotid duplex). Incidental thyroid nodules are contributing to
      but are not the sole reason for the rising incidence of thyroid cancer in the
      Unites States and other developed nations. 

PMID- 24857573
TI  - Follicular lesions of the thyroid.
AB  - Follicular lesions of the thyroid encompass a wide spectrum of diseases with
      clinicopathologic overlap, including benign follicular adenoma, malignant
      follicular carcinoma, and follicular variant of papillary cancer. This review
      addresses the clinical presentation, preoperative diagnosis in the era of
      molecular markers, pathologic diagnosis, treatment, and prognosis of follicular
      lesions, taking into account the frequent controversy about definitive histologic
      diagnoses. 

PMID- 24857574
TI  - The role of genetic markers in the evaluation and management of thyroid nodules.
AB  - Thyroid nodules are common, with increasing incidence, but only 5% to 15% of
      nodules are malignant. Genetic markers should only be used as an ancillary
      diagnostic tool for indeterminate thyroid nodules. Veracyte Afirma may improve
      the diagnostic accuracy for a subset of indeterminate cytologic diagnosis.
      Overall clinical, imaging, and cytopathologic evaluation in addition to patient
      preference should guide the management of indeterminate nodules. Further
      multicentered and independent validation studies are needed in order to prove the
      efficacy of commercially available genetic markers. 

PMID- 24857575
TI  - Prophylactic central compartment neck dissection for papillary thyroid cancer.
AB  - Prophylactic central compartment neck dissection (pCCND) is a CCND in patients
      with thyroid cancer who have no clinical, sonographic, or intraoperative evidence
      of abnormal lymph nodes. Whether pCCND should be performed in all patients with
      clinically node-negative papillary thyroid cancer (PTC) is controversial.
      Existing data reveal that for patients with clinically node-negative PTC there is
      no difference between treatment with total thyroidectomy plus pCCND and total
      thyroidectomy alone. The potential increased risk of hypoparathyroidism
      associated with CCND is not offset by any measurable oncologic benefit.
      Risk/benefit balance favors total thyroidectomy alone for patients with
      clinically node-negative PTC. 

PMID- 24857576
TI  - Medical therapy for advanced forms of thyroid cancer.
AB  - More options than ever before are currently available for medical therapy in
      patients who present with advanced thyroid cancer or develop surgically
      unresectable recurrences or symptomatic or progressive disease. The newer medical
      therapies have addressed the need to find effective therapies beyond the
      conventional treatment with radioactive iodine, thyroid stimulating hormone
      suppression, and palliative cytotoxic chemotherapy for patients with advanced
      thyroid cancer. Although tumor responses to these medical therapies vary by type
      of thyroid cancer and type of therapy selected, they remain encouraging and
      provide therapeutic options for selected patients while new drugs are in
      development. 

PMID- 24857577
TI  - Controversy over radioiodine ablation in thyroid cancer: who benefits?
AB  - Recent studies have proposed that overdiagnosis is probably the principal cause
      of the increased incidence of thyroid cancer. The controversy around radioiodine
      ablation is complicated by the ever increasing numbers of small, low-risk thyroid
      cancers being diagnosed. This article examines the history and evolving
      epidemiology of the disease and treatment. 

PMID- 24857578
TI  - Minimizing cost and maximizing success in the preoperative localization strategy
      for primary hyperparathyroidism.
AB  - Ultrasonography of the thyroid, parathyroid, and soft tissues of the neck should
      always be performed before parathyroidectomy. The most cost-effective
      localization strategies seem to be ultrasonography followed by four-dimensional
      computed tomography (4DCT) or ultrasonography followed by sestamibi +/- 4DCT.
      These localization strategies are highly dependent on the quality of imaging.
      Surgeons should critically evaluate the imaging and operative data at their own
      institution to determine the best preoperative localization strategy before
      parathyroidectomy. Surgeons should communicate with the referring physicians
      about the best localization algorithms in the local area and become the decision
      maker as to when to obtain them. 

PMID- 24857579
TI  - Operative treatment of primary hyperparathyroidism: balancing cost-effectiveness
      with successful outcomes.
AB  - Parathyroidectomy is the most cost-effective treatment for hyperparathyroidism.
      Randomized prospective trials have shown no difference in cure rate between
      focused parathyroidectomy and bilateral exploration. Costs of the two techniques
      differ depending on the preoperative and intraoperative localization used, speed
      of the operation, ability to discharge the patient on the same day as the
      operation, cure rate, and complications. It may be less costly and more effective
      to use a policy of routine 4-gland exploration without the use of preoperative or
      intraoperative localization studies. The potential economic impact and the
      expected outcome of the various strategies should be formally evaluated. 

PMID- 24857580
TI  - Radiographic evaluation of nonfunctioning adrenal neoplasms.
AB  - Incidental adrenal neoplasms are usually nonfunctioning benign adenomas. Once
      hormonal production has been assessed, the nonsecreting lesions must be evaluated
      for the possibility of malignancy. This evaluation relies primarily on the
      radiographic characteristics. This article focuses on the current state of
      radiologic technology available to accurately assess nonfunctioning adrenal
      incidentalomas. As this technology advances, a lesion's malignant potential can
      more accurately be determined, thereby allowing physicians to make more informed
      treatment recommendations. 

PMID- 24857581
TI  - Hyperaldosteronism: diagnosis, lateralization, and treatment.
AB  - Primary hyperaldosteronism is an important and commonly unrecognized secondary
      cause of hypertension. This article provides an overview of the current
      literature with respect to screening, diagnosis, and lateralization. Selection
      and outcomes of medical and surgical treatment are discussed. 

PMID- 24857582
TI  - Subclinical Cushing syndrome: a review.
AB  - Owing to its diagnostic challenges, subclinical Cushing syndrome (SCS) is likely
      to be highly underdiagnosed and undertreated, and the overall incidence may be as
      high as 5% to 20% in patients with adrenal incidentalomas. The diagnosis can be
      established by a systematic and thorough biochemical evaluation. SCS has been
      associated with significant morbidity, which at least partly may be reversed by
      surgery. Given the low rates of complications and the possibility to reverse the
      detrimental effects of elevated cortisol secretion, minimally invasive
      adrenalectomy is recommended for patients with biochemically proven or suspected
      SCS who are appropriate surgical candidates. 

PMID- 24857583
TI  - Adrenocortical cancer update.
AB  - Although preoperative clinical, biochemical, and radiologic features can aid in
      the diagnosis of adrenocortical cancer (ACC), uncertainty often remains. This
      diagnostic ambiguity and the subsequent potential for an inadequate surgical
      resection have likely contributed to the currently dismal disease-free survival,
      although unsettlingly high rates of locoregional recurrences still persist even
      in the setting of a supposedly R0 resection. Refinements in both diagnostic
      criteria and surgical techniques, as well as the increasing use and study of
      novel multimodality therapies for ACC, have provided advances in the treatment of
      these patients, and renewed hope for meaningful improvements in patient outcomes.

PMID- 24857584
TI  - Nonfunctional pancreatic neuroendocrine tumors.
AB  - Pancreatic neuroendocrine tumors are a group of rare, heterogeneous neoplasms
      that have been increasing in incidence the past few decades largely because of
      the diagnosis of pancreatic incidentalomas on cross-sectional imaging. Although
      these tumors are classically associated with clinical syndromes that result from
      excess secretion of particular hormones, most pancreatic neuroendocrine tumors
      are nonfunctional tumors presenting with symptoms secondary to mass effect,
      metastatic disease, or as incidental findings. This article reviews the
      diagnostic algorithm, surgical management, and available systemic therapies for
      nonfunctional pancreatic neuroendocrine tumors. 

PMID- 24857585
TI  - Endocrine surgery.

PMID- 24857586
TI  - Endocrine surgery.

PMID- 24857587
TI  - [Generalized annular granuloma].

PMID- 24857588
TI  - Challenges for lupus management in emerging countries.
AB  - In emerging countries, systemic lupus erythematosus (SLE) has been associated
      with several unfavorable outcomes including disease activity, damage accrual,
      work disability and mortality. Poor socioeconomic status (SES) and lack of access
      to healthcare, especially in medically underserved communities, may be
      responsible for many of the observed disparities. Diagnostic delay of SLE or for
      severe organ damages (renal involvement) have a negative impact on those adverse
      outcomes in lupus patients who either belong to minority groups or live in
      emerging countries. Longitudinal and observational prospective studies and
      registries may help to identify the factors that influence poor SLE outcomes in
      emerging countries. Infection is an important cause of mortality and morbidity in
      SLE, particularly in low SES patients and tuberculosis appears to be frequent in
      SLE patients living in endemic areas (mainly emerging countries). Thus,
      tuberculosis screening should be systematically performed and prophylaxis
      discussed for patients from these areas. SLE treatment in the developing world is
      restricted by the availability and cost of some immunosuppressive drugs.
      Moreover, poor adherence has been associated to bad outcomes in lupus patients
      with a higher risk of flares, morbidity, hospitalization, and poor renal
      prognosis. Low education and the lack of money are identified as the main barrier
      to improve lupus prognosis. Newer therapeutic agents and new protocols had
      contributed to improve survival in SLE. The use of corticoid-sparing agents
      (hydroxychloroquine, methotrexate, azathioprine and mycophenolate mofetif) is one
      of the most useful strategy; availability of inexpensive generics may help to
      optimize access to these medications. 

PMID- 24857589
TI  - In situ analysis of bacterial extracellular polymeric substances from a
      Pseudomonas fluorescens biofilm by combined vibrational and single molecule force
      spectroscopies.
AB  - Extracellular polymeric substances (EPS) play an important role in biofilm
      cohesion and adhesion to surfaces. EPS of a P. fluorescens biofilm were
      characterized through their vibrational spectra (infrared and Raman) and their
      conformational properties using single molecule force spectroscopy with specific
      probes for glucose, galactose, and N-acetyl glucosamine-rich EPS. Vibrational
      spectra evidenced the overproduction of glycogen and other carbohydrates in the
      biofilm. The conformational analysis was performed from both the freely jointed
      chain (FJC) and worm like chain (WLC) models. The results of the FJC fittings
      showed highly ramified and/or folded structures for all the detected EPS with
      molecular elongations up to 1000-2500 nm, and typical Kuhn lengths of glycogen
      macromolecules. The characteristics of galactose-rich EPS have been found to be
      significantly different from those of glucose- and N-acetyl glucosamine-rich EPS.
      On the basis of the theoretical fittings with the WLC model, our results
      suggested that carbohydrates may be associated with peptide domains. 

PMID- 24857591
TI  - Corrigendum.

PMID- 24857592
TI  - A question of ethics: selling autologous stem cell therapies flaunts professional
      standards.
AB  - The idea that the body's own stem cells could act as a repair kit for many
      conditions, including cardiac repair, underpins regenerative medicine. While
      progress is being made, with hundreds of clinical trials underway to evaluate
      possible autologous cell-based therapies, some patients and physicians are not
      prepared to wait and are pursuing treatments without evidence that the proposed
      treatments are effective, or even safe. This article explores the inherent
      tension between patients, practitioners and the need to regulate the development
      and commercialization of new cellular therapies--even when the cells come from
      the patient.

PMID- 24857593
TI  - Geometric nipple reduction technique: an approach to management of nipple
      hypertrophy.

PMID- 24857590
TI  - Generation and characterization of an immortalized human mesenchymal stromal cell
      line.
AB  - Human mesenchymal stromal cells (hMSCs) show great potential for clinical and
      experimental use due to their capacity to self-renew and differentiate into
      multiple mesenchymal lineages. However, disadvantages of primary cultures of
      hMSCs are the limited in vitro lifespan, and the variable properties of cells
      from different donors and over time in culture. In this article, we describe the
      generation of a telomerase-immortalized nontumorigenic human bone marrow-derived
      stromal mesenchymal cell line, and its detailed characterization after long-term
      culturing (up to 155 population doublings). The resulting cell line, iMSC#3,
      maintained a fibroblast-like phenotype comparable to early passages of primary
      hMSCs, and showed no major differences from hMSCs regarding surface marker
      expression. Furthermore, iMSC#3 had a normal karyotype, and high-resolution array
      comparative genomic hybridization confirmed normal copy numbers. The gene
      expression profiles of immortalized and primary hMSCs were also similar, whereas
      the corresponding DNA methylation profiles were more diverse. The cells also had
      proliferation characteristics comparable to primary hMSCs and maintained the
      capacity to differentiate into osteoblasts and adipocytes. A detailed
      characterization of the mRNA and microRNA transcriptomes during adipocyte
      differentiation also showed that the iMSC#3 recapitulates this process at the
      molecular level. In summary, the immortalized mesenchymal cells represent a
      valuable model system that can be used for studies of candidate genes and their
      role in differentiation or oncogenic transformation, and basic studies of
      mesenchymal biology. 

PMID- 24857594
TI  - Ptosis-associated lateral canthus dehiscence and reconstruction.

PMID- 24857595
TI  - Differences between patients and medical professionals in the evaluation of
      aesthetic outcome following breast reconstruction with implants.
AB  - BACKGROUND AND AIM: Most studies on breast reconstruction evaluate different
      surgical techniques, types of implant or time of reconstruction. Moreover,
      evaluations are usually performed either by surgeons or by patients, but are
      rarely compared. We conducted a study on aesthetic outcome following breast
      reconstruction with implants comparing the evaluation by patients versus medical
      professionals. METHODS: Forty-seven patients, who had a breast reconstruction
      with implants between 2001 and 2010 (median follow-up 71 months), underwent a
      clinical examination, standardized photo documentation and filled out a
      questionnaire to evaluate their aesthetic result (rate 1 very good to 5 very
      poor). Photo documentation was independently evaluated by 18 medical
      professionals using the same evaluation instrument and the results were compared.
      Gender and patient aspects were taken into account. RESULTS: We found
      statistically significant differences between patients and medical professional
      ratings. The patient evaluation was better through all categories as compared to
      the evaluation by medical personnel. The degree of medical education or gender
      aspects did not significantly affect the professional ratings. Age at
      reconstruction, length of follow-up or primary versus secondary reconstruction
      did not seem to make a difference in the evaluations of the patients versus the
      medical professionals.. CONCLUSION: The differences between patient and expert
      opinion in rating of aesthetic results indicate that patient satisfaction is
      influenced by multiple factors and not only by good aesthetic outcome. Patient
      evaluation should therefore be carefully considered in treatment and outcome
      studies of breast reconstruction..

PMID- 24857596
TI  - Cisplatin-mediated radiosensitization of non-small cell lung cancer cells is
      stimulated by ATM inhibition.
AB  - BACKGROUND AND PURPOSE: Cisplatin activates ataxia-telangiectasia-mutated (ATM),
      a protein with roles in DNA repair, cell cycle progression and autophagy. We
      investigated the radiosensitizing effect of cisplatin with respect to its effect
      on ATM pathway activation. MATERIAL AND METHODS: Non-small cell lung cancer cells
      (NSCLC) cell lines (A549, H460) and human fibroblast (ATM-deficient AT5, ATM
      proficient 1BR3) cells were used. The effects of cisplatin combined with
      irradiation on ATM pathway activity, clonogenicity, DNA double-strand break (DNA
      DSB) repair and cell cycle progression were analyzed with Western blotting,
      colony formation and gamma-H2AX foci assays as well as FACS analysis,
      respectively. RESULTS: Cisplatin radiosensitized H460 cells, but not A549 cells.
      Radiosensitization of H460 cells was not due to impaired DNA-DSB repair,
      increased apoptosis or cell cycle dysregulation. The lack of radiosensitization
      demonstrated for A549 cells was associated with cisplatin-mediated stimulation of
      ATM (S1981) and AMPKalpha (T172) phosphorylation and autophagy. However, in both
      cell lines inhibition of ATM and autophagy by KU-55933 and chloroquine
      diphosphate (CQ) respectively resulted in a significant radiosensitization.
      Combined treatment with the AMPK inhibitor compound-C led to radiosensitization
      of A549 but not of H460 cells. As compared to the treatment with KU-55933 alone,
      radiosensitivity of A549 cells was markedly stimulated by the combination of KU
      55933 and cisplatin. However, the combination of CQ and cisplatin did not
      modulate the pattern of radiation sensitivity of A549 or H460 cells. In
      accordance with the results that cisplatin via stimulation of ATM activity can
      abrogate its radiosensitizing effect, ATM deficient cells were significantly
      sensitized to ionizing radiation by cisplatin. CONCLUSION: The results obtained
      indicate that ATM targeting can potentiate cisplatin-induced radiosensitization.

PMID- 24857597
TI  - Timeliness of yellow fever surveillance, Central African Republic.
AB  - During January 2007-July 2012, a total of 3,220 suspected yellow fever cases were
      reported in the Central African Republic; 55 were confirmed and 11 case-patients
      died. Mean delay between onset of jaundice and case confirmation was 16.6 days.
      Delay between disease onset and blood collection could be reduced by increasing
      awareness of the population. 

PMID- 24857599
TI  - Food waste in a school nutrition program after implementation of new lunch
      program guidelines.
AB  - OBJECTIVE: To assess the amount of food waste by meal components according to the
      new National School Lunch Program guidelines among pre-kindergarten and
      kindergarten students. METHODS: For 5 consecutive school days in 1 elementary
      school, the research team collected school lunch trays and separated meal
      components into bins relative to each food or beverage appearing on the school's
      daily menu. Bins were weighed in grams and converted to ounces and cups at the
      end of each lunch period. RESULTS: The researchers examined 304 meals from 1 pre
      kindergarten class and 5 kindergarten classes. Of 4,988 oz of food and beverages
      served, 2,261 oz (45.3%) were wasted during 1 full school week, totaling 141 lb.
      The greatest amount of food waste was generated from vegetables, the main entree,
      and milk, respectively. CONCLUSIONS AND IMPLICATIONS: Strategies to reduce food
      waste in school lunch should be researched and implemented.

PMID- 24857600
TI  - The effect of goal setting on fruit and vegetable consumption and physical
      activity level in a Web-based intervention.
AB  - OBJECTIVE: To explore the relationship between goal setting and fruit and
      vegetable (FV) consumption and physical activity (PA) in an intervention for
      college students. METHODS: Secondary data analysis of intervention group
      participants from a 10-week online intervention with complete weekly data (n =
      724). Outcomes (cups of FV per day and minutes of PA per week) and goals for both
      behaviors were reported online each week. Weekly differences between goals and
      behaviors were calculated, as well as the proportion meeting individual goals and
      meeting recommendations for behaviors. RESULTS: There were significant (P < .05)
      effects of goal setting on both behaviors and of goal group (tertile of meeting
      weekly goals) on behavior, as well as meeting recommendations for both behaviors.
      There was an increase in FV consumption (P < .001) but no change in PA over time.
      CONCLUSIONS AND IMPLICATIONS: Goal setting as part of a Web-based intervention
      for college students was effective, but results differed for FV and PA. Goal
      setting for maintaining behavior may need to differ from goal setting for
      changing behavior.

PMID- 24857605
TI  - Recent advances in curcumin nanoformulation for cancer therapy.
AB  - INTRODUCTION: Natural compounds are emerging as effective agents for the
      treatment of malignant diseases. Curcumin (diferuloylmethane), the active
      constituent of turmeric extract, has gained significant interest as a plant-based
      compound with anti-cancer properties. Curcumin is physiologically very well
      tolerated, with negligible systemic toxicity observed even after high oral doses
      administration. Despite curcumin's superior properties as an anti-cancer agent
      its applications are limited due to its low solubility and physico-chemical
      stability, rapid systemic clearance and low cellular uptake. AREAS COVERED: This
      review focuses on the development of curcumin nano-particle formulation to
      improve its therapeutic index through enhanced cellular uptake, localization to
      targeted areas and improved bioavailability. The feasibility of nano-formulation
      in delivering curcumin and the limitations and challenges in designing and
      administrating the nano-sized curcumin particles are also covered in this review.
      EXPERT OPINION: Nanotechnology is a promising tool to enhance efficacy and
      delivery of drugs. In this context, formulation of curcumin as nano-sized
      particles could reduce the required therapeutic dosages and subsequently reduced
      its cell toxicity. These nanoparticles are capable to provide local delivery of
      curcumin targeted to specific areas and thereby preventing systemic clearance. In
      addition, using specific coating, better pharmacokinetic and internalization of
      nano-curcumin could be achieved. However, the potential toxicity of nano-carriers
      for curcumin delivery is an important issue, which should be taken into account
      in curcumin nano-formulation.

PMID- 24857607
TI  - Surgical management of acute cholecystitis. Results of a nation-wide survey among
      Spanish surgeons.
AB  - There is a wide variability in the management of acute cholecystitis. A survey
      among the members of the Spanish Association of Surgeons (AEC) analyzed the
      preferences of Spanish surgeons for its surgical management. The majority of the
      771 responders didn't declare any subspecialty (41.6%), 21% were HPB surgeons,
      followed by colorectal and upper-GI specialities. Early cholecystectomy during
      the first admission is the preferred method of management of 92.3% of surgeons,
      but only 42.7% succeed in adopting this practice. The most frequent reasons for
      changing their preferred practice were: Patients not fit for surgery (43.6%) and
      lack of availability of emergency operating room (35.2%). A total of 88.9%
      perform surgery laparoscopically. The majority of AEC surgeons advise index
      admission cholecystectomy for acute cholecystitis, although only half of them
      succeed in its actual implementation. There is room for improvement in the
      management of acute cholecystitis in Spanish hospitals. 

PMID- 24857608
TI  - Intestinal intussusception due to a lipoma in Meckel's diverticulum.

PMID- 24857609
TI  - The role of sentinel lymph node in colon cancer evolution.
AB  - INTRODUCTION: The aim of this study is to evaluate the sentinel lymph node
      mapping (SLNM) with methylene blue staining "ex vivo" in colon cancer, as well as
      calculate the upstaging obtained by the determination of micrometastases and its
      correlation with the evolution of the disease. METHODS: Between 2008 and 2011,
      101 patients with colon cancer undergoing resection were studied prospectively
      with SLNM and detection of micrometastases. The correlation of SLN
      micrometastases with the disease evolution was evaluated in patients with a
      follow-up of more than one year. RESULTS: The SLNM rate was 92 cases (91%). Only
      SLN was positive for micrometastases in 9 cases, with a 14% upstaging. The
      incidence of false negatives was 9 patients (10%). Mean follow of N0 patients
      (n=74) was 38 months. The SLN- (negative) group (65 patients) had a recurrence
      rate of 4 patients (7%), whereas this rate was 2 patients (22%) in the group of
      SLN+(positive) (9 patients), but without significant differences. No differences
      in survival were observed. CONCLUSIONS: SLNM is a reproducible technique without
      significant increase in time and costs. Upstaging was obtained in 14% of patients
      staged as N0 by conventional technique. At follow-up of N0 patients with
      SLN+there seems to be a higher rate of recurrence, which could change the
      guidelines of adjuvant treatment, but we must interpret the results it with
      caution because the sample is small.

PMID- 24857610
TI  - Are mental disorders more common in urban than rural areas of the United States?
AB  - Urban vs. rural residence is commonly cited as a risk factor for depression and
      other mental disorders, but epidemiological evidence for this relationship in the
      US is inconclusive. We examined three consecutive annual samples (2009-2011) of
      adolescents (age 12-17, N = 55,583) and adults (age 18 and over, N = 116,459)
      from the National Survey of Drug Use and Health (NSDUH) to compare the prevalence
      of major depression and other serious mental illness across four categories of
      urbanicity: (1) large metropolitan areas, (2) small metropolitan areas, (3) semi
      rural areas, and (4) rural areas, with and without adjustment for other
      demographic risk factors. For adolescents, no association was observed between
      urbanicity and the prevalence of major depression, with or without statistical
      adjustments. For adults, no differences were found in the prevalence of major
      depression or serious mental illness between large metropolitan areas and rural
      areas, but the prevalence of both was slightly higher in the two intermediate
      urbanicity categories than in large metropolitan areas, with statistically
      significant odds ratios after adjustment ranging from 1.12 to 1.19. Contrary to
      expectations, the prevalence of mental disorders was not higher in the most urban
      compared with the most rural areas, suggesting that the move to identify
      mechanistic explanations for risk associated with the urban environment is
      premature. Evidence of slightly higher prevalence in small urban and semi-rural
      areas relative to large urban areas, reported for the first time, requires
      additional investigation.

PMID- 24857611
TI  - Terminal residue hydrophobicity modulates transmembrane helix-helix interactions.
AB  - Central to the formation of tertiary structure in membrane protein folding is the
      presence of amino acid sequence motifs (such as "small-XXX-small" segments) in
      the TM segments that promote interaction-compatible surfaces through which the TM
      alpha-helices interact. Here, we sought to elucidate additional factors that may
      work in tandem to dictate the ultimate interaction fate of TM-embedded segments.
      In this context, we used proteolipid protein (PLP), the major protein from
      central nervous system myelin for which mutant-dependent non-native
      oligomerization has been implicated in neurological disorders, to explore the
      specific effects of TM boundary residues (the membrane entry and exit points),
      keying on the secondary structure and self-association of peptides corresponding
      to the PLP TM2 alpha-helix (wild-type sequence 66AFQYVIYGTASFFFLYGALLLAEGF90).
      Using gel electrophoresis, circular dichroism, and Forster resonance energy
      transfer in the membrane-mimetic detergent sodium dodecyl sulfate (SDS), we found
      that mutation of F90 to residues such as A, I, L, or V maintains the onset of TM2
      TM2 dimerization, whereas mutation to E, G, Q, N, S, or T abrogates dimer
      formation. We attribute this sensitivity to changes in local hydrophobicity,
      viz., a decrease in hydrophobicity reduces local lipid-peptide interactions,
      which in turn disrupts peptide alpha-helicity and hence the effectiveness of an
      incipient interaction-compatible surface. Our results show that the secondary
      structure and oligomeric state of PLP TM2 Lys-tagged peptides are significantly
      modulated by the specific nature of their C-terminal boundary residue, thus
      providing insight as to how point mutations, particularly where they produce
      disease states, can compromise the folding process.

PMID- 24857612
TI  - Coming home to die? The association between migration and mortality in rural
      Tanzania before and after ART scale-up.
AB  - BACKGROUND: Prior to the scale-up of antiretroviral therapy (ART), demographic
      surveillance cohort studies showed higher mortality among migrants than residents
      in many rural areas. OBJECTIVES: This study quantifies the overall and AIDS
      specific mortality between migrants and residents prior to ART, during ART scale
      up, and after widespread availability of ART in Rufiji district in Tanzania.
      DESIGN: In Health and Demographic Surveillance System (HDSS), the follow-up of
      individuals aged 15-59 years was categorized into three periods: before ART (1998
      2003), during ART scale-up (2004-2007), and after widespread availability of ART
      (2008-2011). Residents were those who never migrated within and beyond HDSS,
      internal migrants were those who moved within the HDSS, and external migrants
      were those who moved into the HDSS from outside. Mortality rates were estimated
      from deaths and person-years of observations calculated in each time period.
      Hazard ratios were estimated to compare mortality between migrants and residents.
      AIDS deaths were identified from verbal autopsy, and the odds ratio of dying from
      AIDS between migrants and residents was estimated using the multivariate logistic
      regression model. RESULTS: Internal and external migrants experienced higher
      overall mortality than residents before the introduction of ART. After widespread
      availability of ART overall mortality were similar for internal and external
      migrants. These overall mortality experiences observed were similar for males and
      females. In the multivariate logistic regression model, adjusting for age, sex,
      education, and social economic status, internal migrants had similar likelihood
      of dying from AIDS as residents (adjusted odds ratio [AOR]=1.14, 95% confidence
      interval [CI]: 0.70-1.87) while external migrants were 70% more likely to die
      from AIDS compared to residents prior to the introduction of ART (AOR=1.70, 95%
      CI: 1.06-2.73). After widespread availability of ART with the same adjustment
      factors, the odds of dying from AIDS were similar for internal migrants and
      residents (AOR=1.56, 95% CI: 0.80-3.04) and external migrants and residents
      (AOR=1.42, 95% CI: 0.76-2.66). CONCLUSIONS: Availability of ART has reduced the
      number of HIV-infected migrants who would otherwise return home to die. This has
      reduced the burden on rural communities who had cared for the return external
      migrants.

PMID- 24857615
TI  - Continuing, rapid change: the hallmark of spine oncology.

PMID- 24857613
TI  - The Bandim TBscore--reliability, further development, and evaluation of potential
      uses.
AB  - BACKGROUND: The tuberculosis (TB) case detection rate has stagnated at 60% due to
      disorganized case finding and insensitivity of sputum smear microscopy. Of the
      identified TB cases, 4% die while being treated, monitored with tools that
      insufficiently predict failure/mortality. OBJECTIVE: To explore the TBscore, a
      recently proposed clinical severity measure for pulmonary TB (PTB) patients, and
      to refine, validate, and investigate its place in case finding. DESIGN: The
      TBscore's inter-observer agreement was assessed and compared to the Karnofsky
      Performance Score (KPS) (paper I). The TBscore's variables underlying constructs
      were assessed, sorting out unrelated items, proposing a more easily assessable
      TBscoreII, which was validated internally and externally (paper II). Finally,
      TBscore and TBscoreII's place in PTB-screening was examined in paper III.
      RESULTS: The inter-observer variability when grading PTB patients into severity
      classes was moderate for both TBscore (kappaW=0.52, 95% CI 0.46-0.56) and KPS
      (kappaW=0.49, 95% CI 0.33-0.65). KPS was influenced by HIV status, whereas
      TBscore was unaffected by it. In paper II, proposed TBscoreII was validated
      internally, in Guinea-Bissau, and externally, in Ethiopia. In both settings, a
      failure to bring down the score by >=25% from baseline to 2 months of treatment
      predicted subsequent failure (p=0.007). Finally, in paper III, TBscore and
      TBscoreII were assessed in health-care-seeking adults and found to be higher in
      PTB-diagnosed patients, 4.9 (95% CI 4.6-5.2) and 3.9 (95% CI 3.8-4.0),
      respectively, versus patients not diagnosed with PTB, 3.0 (95% CI 2.7-3.2) and
      2.4 (95% CI 2.3-2.5), respectively. Had we referred only patients with cough >2
      weeks to sputum smear, we would have missed 32.1% of the smear confirmed cases in
      our cohort. A TBscoreII>=2 missed 8.6%. CONCLUSIONS: TBscore and TBscoreII are
      useful monitoring tools for PTB patients on treatment, as they could fill the
      void which currently exists in risk grading of patients. They may also have a
      role in PTB screening; however, this requires our findings to be repeated
      elsewhere.

PMID- 24857614
TI  - Bufavirus in feces of patients with gastroenteritis, Finland.

PMID- 24857616
TI  - The management of malignant spinal cord compression: a modified technique of
      spinal reconstruction.
AB  - OBJECTIVES: This study aims to assess the results of a single-stage
      posterolateral transpedicular corpectomy and fusion in malignant spinal cord
      compression of the thoracolumbar spine. METHODS: Sixteen cases of thoracolumbar
      metastases were treated with single-stage posterolateral transpedicular
      corpectomy and fusion. A modified technique of nerve preserving bilateral cage
      placement was described. Pain, American Spinal Injury Association (ASIA) scores,
      spinal deformity, primary pathologies, and survival were recorded. RESULTS: The
      most common primary pathology was lung, followed by renal and colorectal cancer.
      Significant pain reduction was achieved in all patients, regardless of previous
      nonsurgical treatment. No patient suffered neurological deterioration after
      surgery. For the 10 patients who presented with neurological deficits, 90%
      improved after surgery. Significant improvement in Cobb angle and vertebral
      height were observed postoperatively. A mean survival of 5.6 months was recorded
      at the completion of this manuscript. DISCUSSION: Single-stage posterolateral
      transpedicular corpectomy and fusion appeared to be a safe and an effective
      approach in malignant spinal cord compression. The current modified technique
      extends its application to lumbar spine by preserving all nerve roots. The
      significant improvement of pain and neurological deficits leads to better quality
      of life. The benefits of surgery in the overall survival remain to be
      investigated.

PMID- 24857619
TI  - Interferon-beta plus ribavirin therapy can be safely and effectively administered
      to elderly patients with chronic hepatitis C.
AB  - AIM: This study aims to evaluate the efficacy and safety of interferon-beta plus
      ribavirin therapy in older Japanese patients. PATIENTS AND METHODS: This study
      enrolled 132 older patients (age, >=65 years) with chronic hepatitis C who
      received 24-48 weeks of interferon-beta plus ribavirin (FR; n = 66) or pegylated
      interferon-alpha plus ribavirin (PR; n = 66) therapy. RESULTS: Patients with the
      ITPA genotype (CA/AA) in the PR group had significantly greater decreases in
      hemoglobin levels than those in the FR group at or after week 8. The proportions
      of patients with a dose reduction of interferon-beta and ribavirin in the FR
      group were significantly lower than those in the PR group. A significantly higher
      proportion of patients completed treatment in the FR group than in the PR group.
      The sustained virological response (intention-to-treat analysis) rate of naive
      patients with genotype 1 was 29% (6 of 21) in the PR group and 29% (6 of 21) in
      the FR group. The sustained virological response (intention-to-treat) rate of
      those with genotype 2 was 67% (12 of 18) in the PR group and 72% (13 of 18) in
      the FR group. CONCLUSION: Interferon-beta plus ribavirin therapy was safe in
      elderly patients, with lower proportions of patients with a dose reduction of
      interferon-beta or ribavirin and treatment discontinuation. In treatment-naive
      patients, the sustained virological response rate was similar between interferon
      beta plus ribavirin therapy and pegylated interferon-alpha plus ribavirin
      therapy, regardless of whether the patients had hepatitis C virus genotype 1 or
      2.

PMID- 24857620
TI  - Methotrexate in juvenile idiopathic arthritis: towards tailor-made treatment.
AB  - Methotrexate (MTX) is the key treatment in juvenile idiopathic arthritis (JIA).
      Nevertheless, MTX is not always sufficiently efficacious and can lead to adverse
      effects, which compromises complete disease control. In such cases, combination
      therapies with biologicals are given, even at MTX start, before knowing the
      patients' MTX response. Ideally, clinicians should be able to practice precision
      medicine by knowing before or early after MTX start, which patients will benefit
      from MTX only and which patients will not, thus requiring addition of
      biologicals. To make such tailor-made treatment decisions, clinicians require
      tools to optimize MTX treatment. In this review, we focus on tools for tailor
      made MTX treatment in JIA.

PMID- 24857621
TI  - The adsorption of pharmaceutically active compounds from aqueous solutions onto
      activated carbons.
AB  - In this study, the adsorption of pharmaceutically active compounds - salicylic
      acid, acetylsalicylic acid, atenolol and diclofenac-Na onto activated carbons has
      been studied. Three different commercial activated carbons, possessing ~650, 900
      or 1500m(2)g(-1) surface areas were used as solid adsorbents. These materials
      were fully characterized - their textural, surface features and points of zero
      charge have been determined. The adsorption was studied from aqueous solutions at
      303K using batch adsorption experiments and titration microcalorimetry, which was
      employed in order to obtain the heats evolved as a result of adsorption. The
      maximal adsorption capacities of investigated solids for all target
      pharmaceuticals are in the range of 10(-4)molg(-1). The obtained maximal
      retention capacities are correlated with the textural properties of applied
      activated carbon. The roles of acid/base features of activated carbons and of
      molecular structures of adsorbate molecules have been discussed. The obtained
      results enabled to estimate the possibility to use the activated carbons in the
      removal of pharmaceuticals by adsorption. 

PMID- 24857622
TI  - IL-17F but not IL-17A gene polymorphism confers risk to multiple sclerosis in a
      Chinese Han population.
AB  - Interleukin-17 has been shown to be associated with autoimmune disease. The aim
      of the current study is to investigate the potential association of IL-17
      polymorphisms with multiple sclerosis (MS) in Chinese Han patients. Two SNPs,
      rs763780 of IL-17F gene and rs2275913 of IL-17A gene were genotyped in 622 MS
      patients and 743 healthy controls by using a polymerase chain reaction
      restriction fragment length polymorphism method (PCR-RFLP). Allele and genotype
      frequencies distribution of the two SNPs were examined between patients and
      controls using the Chi-Square test. All genotypic and allelic frequencies of the
      tested IL-17 polymorphisms in control cohort were in Hardy-Weinberg equilibrium.
      A significantly increased frequency of rs763780 TT genotype (corrected p value
      (Pc)=0.024, odds ratio=1.472, 95% CI=1.133-1.913) and T allele (corrected P
      (Pc)=0.018, odds ratio=1.446, 95% CI=1.134-1.844) was detected in MS patients
      compared with controls. The genotypic and allelic frequencies of rs2275913 in IL
      17A gene were not different between patients with MS and controls. These results
      suggest that rs763780 is associated with multiple sclerosis in a Chinese Han
      population. 

PMID- 24857623
TI  - Blood transfusion-related posterior reversible encephalopathy syndrome.
AB  - Neurological complications have rarely been described after blood transfusion.
      Posterior reversible encephalopathy syndrome (PRES) is a recently recognized
      entity affecting predominantly the posterior cerebral hemispheres. We report two
      distinctive cases with history of chronic anemia that developed headache, blurred
      vision and seizure after blood transfusion. Magnetic resonance imaging indicated
      vasogenic edema consistent with PRES. 

PMID- 24857624
TI  - Electromechanical sensing of substrate charge hidden under atomic 2D crystals.
AB  - The functionality of graphene and other two-dimensional materials in electronic
      devices is highly influenced by the film-substrate charge transfer affecting
      local carrier density. We demonstrate that charges buried under the few layer
      graphene on/in the insulating substrate can be detected using electromechanical
      actuation of the conductive atomically thin layers, allowing measurements of
      areal density of film-substrate transferred charges under few layer graphene and
      MoS2 suspended films. 

PMID- 24857625
TI  - Promoting family-focused approaches within adult drug services: the potential of
      the 'Senses Framework'.
AB  - BACKGROUND: Policies across countries promote family-focused engagement with
      adult drugs services however this is rarely offered routinely and relationships
      with carers are often poor. Research in mental health and older people's services
      suggests that improving the relationships between carers and service providers is
      fundamental to enhancing the quality of services. One example is the Senses
      Framework which assesses the extent to which services are relationship-centred
      and provides deeper insight into the areas that require further improvement. The
      aim of this paper is to establish the extent to which relationship-centred care,
      as defined by the Senses Framework, is expressed in the interactions between
      carers, services providers and policy makers in adult drug service settings.
      METHODS: A qualitative study, involving 8 focus groups and 32 individual
      interviews, was undertaken to explore carers', service providers' and policy
      makers' experiences and understandings of family and carer involvement with drug
      services in Scotland, United Kingdom. RESULTS: Tensions exist between carers,
      service providers and policy makers however there are also areas of commonality
      in which participants shared experiences and understandings of family and carer
      involvement with services. Our findings go beyond existing research which focuses
      largely on describing of the poor quality of relationships between carers,
      service providers and policy makers by providing a deeper theoretical insight
      into the nature of these relationships. In so doing, by focusing on the senses of
      belonging, continuity, security, achievement, purpose and significance, we
      present the possibility of resolving such tensions. CONCLUSIONS: We think that
      implementing relationship-centred approaches to care, such as that in the Senses
      Framework, would provide a greater sense of therapeutic and strategic direction
      for those delivering and commissioning adult drug services in many countries.

PMID- 24857626
TI  - Dual false positive of 68Ga-DOTA-TATE PET/CT scan in a patient with a history of
      pancreatic neuroendocrine tumor: a case report.

PMID- 24857627
TI  - Dynamic modeling of sublethal mixture toxicity in the nematode Caenorhabditis
      elegans.
AB  - Dynamic models for toxic effects [toxicokinetic-toxicodynamic (TKTD) models] are
      increasingly used in the analysis of toxicity data for single-chemical exposure.
      However, these models also offer a natural extension to the effects of chemical
      mixtures. Here, we demonstrate how a simple model for the energy budget (DEBkiss)
      can be used to interpret the effects of cadmium and fluoranthene, in both single
      and mixed exposure, on the nematode Caenorhabditis elegans. The data for all time
      points and all end points (growth and reproduction) are combined into a single
      coherent framework. These modeling results are compared to a more traditional
      independent-action approach based on the dose-response curves for a single end
      point at a single time point. The analysis with DEBkiss does not lead to a
      radically different interpretation of the mixture effects, both indicating an
      antagonistic interaction in the mixture. The DEBkiss analysis does, however,
      provide much more insight into the relevant dynamic processes underlying the
      toxic effect on the organism and allows for the generation of mechanistic
      hypotheses that can be used to guide further research. 

PMID- 24857628
TI  - Gastrulation and the establishment of the three germ layers in the early horse
      conceptus.
AB  - Experimental studies and field surveys suggest that embryonic loss during the
      first 6 weeks of gestation is a common occurrence in the mare. During the first 2
      weeks of development, a number of important cell differentiation events must
      occur to yield a viable embryo proper containing all three major germ layers
      (ectoderm, mesoderm, and endoderm). Because formation of the mesoderm and
      primitive streak are critical to the development of the embryo proper, but have
      not been described extensively in the horse, we examined tissue development and
      differentiation in early horse conceptuses using a combination of
      stereomicroscopy, light microscopy, and immunohistochemistry. Ingression of
      epiblast cells to form the mesoderm was first observed on day 12 after ovulation;
      by Day 18 the conceptus had completed a series of differentiation events and
      morphologic changes that yielded an embryo proper with a functional circulation.
      While mesoderm precursor cells were present from Day 12 after ovulation, vimentin
      expression was not detectable until Day 14, suggesting that initial
      differentiation of mesoderm from the epiblast in the horse is independent of this
      intermediate filament protein, a situation that contrasts with other domestic
      species. Development of the other major embryonic germ layers was similar to
      other species. For example, ectodermal cells expressed cytokeratins, and there
      was a clear demarcation in staining intensity between embryonic ectoderm and
      trophectoderm. Hypoblast showed clear alpha1-fetoprotein expression from as early
      as Day 10 after ovulation, and seemed to be the only source of alpha1-fetoprotein
      in the early conceptus.

PMID- 24857629
TI  - Dense spermatozoa in stallion ejaculates contain lower concentrations of mRNAs
      encoding the sperm specific calcium channel 1, ornithine decarboxylase antizyme
      3, aromatase, and estrogen receptor alpha than less dense spermatozoa.
AB  - Stallions are unique among livestock in that, like men, they commonly receive
      medical treatment for subfertility. In both species, about 15% of individuals
      have normal semen parameters but are subfertile, indicating a need for novel
      analyses of spermatozoa function. One procedure for improving fertilizing
      capability of stallions and men is isolation of dense spermatozoa from an
      ejaculate for use in artificial insemination. In the current study, dense and
      less dense spermatozoa were purified by density gradient centrifugation from
      individual ejaculates from seven reproductively normal adult stallions. The RNA
      isolated from the spermatozoa seemed to be naturally fragmented to an average
      length of 250 bases, consistent with reports of spermatozoa RNA from other
      species. The DNAse treatment of RNA prepared from spermatozoa removed any genomic
      DNA contamination, as assessed by PCR with intron spanning primers for the
      protamine 1 (PRM1) gene. Concentrations of seven mRNAs in spermatozoa, correlated
      with the fertility of men and bulls, were quantified by reverse transcription
      polymerase chain reaction in dense and less dense spermatozoa. Concentrations of
      four mRNAs were two- to four-fold lower in dense spermatozoa compared with less
      dense spermatozoa: Encoding the spermatozoa-specific calcium channel (P < 0.03),
      ornithine decarboxylase antizyme 3 (P < 0.02), aromatase (P < 0.02), and estrogen
      receptor alpha (P < 0.08). In contrast, concentrations of three other mRNAs,
      encoding PRM1 and heat shock proteins HSPA8 and DNAJC4, were not different (P >
      0.1). These results identify new differences in mRNA concentrations in
      populations of spermatozoa with dissimilar densities.

PMID- 24857630
TI  - [Prevalence of burnout syndrome and its associated factors in Primary Care
      staff].
AB  - INTRODUCTION: Burnout syndrome is an emerging disease among health professionals.
      The aim of this study is to determine the prevalence of occupational burnout
      among Primary Care staff, as well as to determine the differences in prevalence
      between family doctors, paediatricians, nurses, administrative-officers, and
      social-workers, and to evaluate the different related factors. MATERIALS AND
      METHODS: A cross-sectional, descriptive study was conducted on 178 professionals
      from 5 different occupational groups in 54 Primary Care centres in Navarre from
      September to December 2010. An anonymous, self-administered questionnaire that
      included: the Maslach Burnout Inventory and a questionnaire on socio-demographic
      and work-related factors. RESULTS: Burnout was detected in 39.3% of staff. Those
      with higher levels are administrative-officers and family doctors, with an OR
      compared to nurses of 4.58 and 5.37, respectively in the dimension of emotional
      exhaustion, 4.98 and 2.87 in depersonalization, and 8.37 for administrative
      officers in personal accomplishment. An association was found between burnout and
      the following factors: to be a male (for the dimensions of emotional exhaustion
      and depersonalization, 25.5 and 31.9%, respectively), to be employed in an urban
      area (for emotional exhaustion and depersonalization, 20 and 27.8%,
      respectively), use of psychiatric medication (for emotional exhaustion, 30%),
      size of patient-quota (for depersonalization, with an average of 1,565 patients),
      and welfare pressure (for emotional exhaustion and depersonalization, averages of
      170.35 and 153.54 patients/week, respectively). CONCLUSIONS: About one-third of
      Primary Care professionals have a high level of burnout, which is mainly
      associated with the working area, the size of the quota, and professional group,
      with higher prevalence in administrative-officers and family doctors.

PMID- 24857631
TI  - Dual histamine H3R/serotonin 5-HT4R ligands with antiamnesic properties:
      pharmacophore-based virtual screening and polypharmacology.
AB  - In recent years, preclinical and clinical studies have generated considerable
      interest in the development of histamine H3 receptor (H3R) antagonists as novel
      treatment for degenerative disorders associated with impaired cholinergic
      function. To identify novel scaffolds for H3R antagonism, a common feature-based
      pharmacophore model was developed and used to screen the 17,194 compounds of the
      CERMN (Centre d'Etudes et de Recherche sur le Medicament de Normandie) chemical
      library. Out of 268 virtual hits which have been gathered in 34 clusters, we were
      particularly interested in tricyclic derivatives also exhibiting a potent 5HT4R
      affinity. Benzo[h][1,6]naphthyridine derivatives showed the highest H3R affinity,
      and compound 17 (H3R Ki = 41.6 nM; 5-HT4R Ki = 208 nM) completely reversed the
      amnesiant effect of scopolamine at 3 mg/kg in a spatial working memory
      experiment. For the first time we demonstrated the feasibility to combine H3R and
      5-HT4R activities in a single molecule, raising the exciting possibility that
      dual H3R antagonist/5HT4R agonist have potential for the treatment of
      neurodegenerative diseases such as Alzheimer's disease. 

PMID- 24857632
TI  - A new approach based on Machine Learning for predicting corneal curvature (K1)
      and astigmatism in patients with keratoconus after intracorneal ring
      implantation.
AB  - Keratoconus (KC) is the most common type of corneal ectasia. A corneal
      transplantation was the treatment of choice until the last decade. However, intra
      corneal ring implantation has become more and more common, and it is commonly
      used to treat KC thus avoiding a corneal transplantation. This work proposes a
      new approach based on Machine Learning to predict the vision gain of KC patients
      after ring implantation. That vision gain is assessed by means of the corneal
      curvature and the astigmatism. Different models were proposed; the best results
      were achieved by an artificial neural network based on the Multilayer Perceptron.
      The error provided by the best model was 0.97D of corneal curvature and 0.93D of
      astigmatism. 

PMID- 24857633
TI  - A Canadian perspective on addiction treatment.
AB  - This paper presents a synopsis of addiction treatment in Canada, along with some
      available comparative figures with other North American countries. Within the
      framework of Canada's Medicare, a largely single-payer system, addiction and
      psychiatric disorders are insured on par with other medical disorders. Canada's
      strategy recognizes the four pillars of prevention, treatment, harm reduction,
      and enforcement. The Canadian Alcohol and Drug Use Monitoring Survey is the
      yearly main source of data on alcohol and illicit drug use. The main features of
      the Canadian addiction treatment network are identified as a "top 10" list,
      outlining early identification and intervention, assessment, and referral;
      detoxification; ambulatory care/day treatment programs; residential care;
      hospitals; concurrent disorders networks and regionalization; drug specific
      strategies; mutual help; behavioral addictions; and training, qualification, and
      research.

PMID- 24857634
TI  - [Dislocation of the thumb extensor tendons: an anatomical, clinical study and new
      classification].
AB  - The authors report on 11 cases of ulnar dislocation of the extensor pollicis
      longus (EPL) due to rupture of the dorsal aponeurosis at the thumb
      metacarpophalangeal (MCP) joint. This condition is rare. By performing a
      descriptive study of this injury, we were able to establish a classification
      system for thumb extensor tendon dislocation. The series included 11 patients
      with a mean age of 27years. All patients presented with either varus or
      rotational thumb injury. This resulted in an active extension deficit in the
      thumb MCP joint with EPL dislocation behind the MCP. Surgery was required in all
      cases. We defined three different injury presentations: 1) dissociated form with
      isolated EPL dislocation, but the EPB still in place; 2) complete form with
      dislocation of both tendons on the ulnar side of the MCP; 3) dissociated or
      complete form associated with a severe sprain of the lateral collateral ligament
      of the thumb MCP joint. The surgical treatment was adapted to each case. A
      classification into three types of dislocation of the extensor tendons at the MCP
      joint of the thumb was established. This rare condition must be identified at the
      time of thumb MCP joint injury and also when harvesting the EPB. This new
      classification system has a diagnostic and therapeutic role as it precisely
      describes the dislocation type and the resulting damage. Only a surgical
      treatment can produce good repairs. 

PMID- 24857635
TI  - Can ring finger injuries be prevented by pre-weakened rings? Three clinical
      cases.
AB  - Prevention of finger trauma can be directly related to the manufacture of pre
      weakened rings. We report on three clinical cases of finger injuries caused by
      pre-weakened rings. Lesions were less severe than conventional ring finger
      injuries, such as those caused by iron fences. Surgery was required in all three
      cases and chronic cold sensitivity was noted in one case. This small series
      advocates the imposition of a ring manufacturing standard at the European level.
      Given this lack of consensus, the idea is to prevent injuries by developing rings
      with intentional weak points that open automatically in case of trauma. These pre
      weakened rings have never been subject to clinical study to demonstrate their
      potential safety. 

PMID- 24857636
TI  - The MetaHUS((r)) fixation system versus pinning and plating in 5th metacarpal
      neck fractures.
AB  - The treatment of fifth metacarpal neck fractures is controversial. The aim of
      this work was to modify the intermetacarpal pinning technique with an external
      connector, and to compare the results of this modified technique to those of
      intramedullary pinning and locking plate techniques. Our series included 56 extra
      articular fractures of the neck of the fifth metacarpal treated by intramedullary
      pinning (group A), locking plate Aptus((r)) MEDARTISTM (group B) and MetaHUS((r))
      ArexTM (group C); the last one consisted in intermetacarpal percutaneous pinning
      and connecting the pins externally. There were no statistically significant
      differences for all criteria except active mobility, which was less important for
      group B. In groups A and B, 6 complications were noted, in group C, one. Our
      results showed that blocked intermetacarpal K-wires is a technique of choice for
      the treatment of displaced fifth metacarpal neck fractures, not only because it
      is easy to assemble and to remove, but also because it allows immediate active
      mobilization.

PMID- 24857638
TI  - Why does substitution of thymine by 6-ethynylpyridone increase the
      thermostability of DNA double helices?
AB  - Efficiency of 6-ethynylpyridone (E), a potential thymine (T) analogue, which
      forms high-fidelity base pairs with adenine (A) and gives rise to stabler DNA
      duplexes, with stability comparable to those containing canonical
      cytosine(C):guanine(G) base pairs, has been reported recently. Estimates of the
      interaction energies, involving geometry optimization at the DFT level (including
      middle range dispersion interactions) followed by single point energy calculation
      at MP2 level, in excellent correlation with the experimentally observed trends,
      show that E binds more strongly and more discriminately with A than T does.
      Detailed analysis reveals that the increase in base-base interaction arises out
      of conjugation of acetylenic pi electrons with the ring pi system of E, which
      results in not only an extra stabilizing C-H...pi interaction in the EA pair, but
      also a strengthening of the conventional hydrogen bonds. However, the computed
      base-base interaction energy for the EA pair was found to be much less than that
      of the canonical CG pair, implying that the difference in the TA versus EA base
      pairing interaction alone cannot explain the large experimentally observed
      increase in the thermostability of DNA duplexes, where a TA pair is replaced with
      an EA pair. Our computations show that the conjugation of acetylenic pi electrons
      with the ring pi system also possibly plays a role in increasing the stacking
      potential of the EA pair, which in turn can explain its marked influence in the
      enhancement of duplex stability. 

PMID- 24857637
TI  - Myristoylated Alanine Rich C Kinase Substrate (MARCKS) is essential to beta2
      integrin dependent responses of equine neutrophils.
AB  - Neutrophil infiltration is a prominent feature in a number of pathologic
      conditions affecting horses including recurrent airway obstruction, ischemia
      reperfusion injury, and laminitis. Cell signaling components involved in
      neutrophil migration represent targets for novel anti-inflammatory therapies. In
      order to migrate into tissue, neutrophils must respond to chemoattractant signals
      in their external environment through activation of adhesion receptors (i.e.
      integrins) and reorganization of the actin cytoskeleton. Myristoylated Alanine
      Rich C-Kinase Substrate (MARCKS), a highly conserved actin-binding protein, has a
      well demonstrated role in cytoskeletal dependent cellular functions (i.e.
      adhesion, spreading, and migration), but the details of MARCKS involvement in
      these processes remain vague. We hypothesized that MARCKS serves as a link
      between the actin cytoskeleton and integrin function in neutrophils. Using a
      MARCKS-specific inhibitor peptide known as MANS on equine neutrophils in vitro,
      we demonstrate that inhibition of MARCKS function significantly attenuates beta2
      integrin-dependent neutrophil functions including migration, adhesion, and immune
      complex-mediated respiratory burst. The MANS peptide did not, however, inhibit
      the beta2-integrin-independent PMA mediated respiratory burst. These results
      attest to the essential role of MARCKS function in regulating neutrophil
      responses, and strongly implicate MARCKS as a potential regulator of beta2
      integrins in neutrophils. 

PMID- 24857639
TI  - Diagnostic accuracy of central venous saturation in estimating mixed venous
      saturation is proportional to cardiac performance among cardiac surgical
      patients.
AB  - PURPOSE: Advanced hemodynamic monitoring in cardiac surgery translates into
      improvement in outcomes. We evaluated the relationship between central venous
      (ScvO2) and mixed venous (SvO2) saturations over the early postoperative period.
      The adequacy of their interchangeability was tested in patients with varying
      degrees of cardiac performance. METHODS: In this prospective observational study,
      we evaluated 156 consecutive cardiac surgical patients in an academic center. The
      ScvO2 and SvO2 data were harvested from 468 paired samples taken preoperatively
      (T0), after weaning from cardiopulmonary bypass (T1) and on postoperative day 1
      (T2). RESULTS: The relationship between ScvO2 and SvO2 was inconsistent, with
      inferior correlations in patients with lower cardiac indices (CI) (Pearson r(2) =
      0.37 if CI <=2.0 L/min per square meter vs r(2) = 0.73 if CI >2.0 L/min per
      square meter, both P < .01). Patients with lower CI also had wider 95% limits of
      agreement between SvO2 and ScvO2. The proportion of patients with a negative SvO2
      ScvO2 gradient increased over time (48/156 [31%] at T0 to 73/156 [47%] at T2; P <
      .01). This subgroup more frequently required inotropes at T2 than patients with a
      positive SvO2-ScvO2 gradient (odds ratio, 6.46 [95% confidence interval, 0.81
      51.87], P = .06) and also had higher serum lactate levels (1.5 +/- 0.8 vs 1.0 +/-
      0.4; P < .01). CONCLUSIONS: The diagnostic accuracy of ScvO2 for estimating SvO2
      is proportional to cardiac performance. A negative SvO2-ScvO2 gradient at T2
      correlated with inotropic support requirement, higher operative risk score, age,
      lactate level, and duration of cardiopulmonary bypass.

PMID- 24857640
TI  - Critically ill cancer patient in intensive care unit: issues that arise.
AB  - Advances in the management of malignancies and organ failures have led to
      substantial increases in survival as well as in the number of cancer patients
      requiring intensive care unit (ICU) admission. Although effectiveness of ICU in
      this group remains controversial, the heterogeneity of its population in terms of
      the nature and curability of their disease and the severity of critical illness
      and underlying conditions may explain the plethora of issues arising when
      considering cancer patients for ICU admission, especially from the view of
      limited resources and ICU beds. The most frequent reasons leading a cancer
      patient to ICU are postoperative, respiratory failure, infection, and sepsis.
      Although reasons of admission, nature and number of organ failures, type of
      malignancy, and therapies that have preceded ICU admission may affect outcome,
      reliable scoring systems or survival predictors are missing. Literature suggests
      that organ dysfunction should be managed at its onset, whereas aggressive ICU
      management should be reappraised after a few days of full support. A
      multidisciplinary treating team of physicians should aid in changing the goals
      from restorative to palliative care when there appears to be no possible benefit
      from any treatment. End-of life-decisions and code status should be made by
      consensus, based on patients' autonomy and dignity. Further interventional
      multicenter studies are required to assess post-ICU burden, long-term medical
      outcomes, and quality of life in this cohort of patients. 

PMID- 24857641
TI  - Mortality benefit of vasopressor and inotropic agents in septic shock: a Bayesian
      network meta-analysis of randomized controlled trials.
AB  - OBJECTIVE: The choice of vasopressor in septic shock has been a matter of debate.
      The purpose of this study was to systematically review overall evidence of
      vasopressor and inotropic agents in septic shock using a Bayesian network meta
      analysis. METHODS: Databases, including Medline, Scopus, CINAHL, and Google
      Scholar were searched to identify relevant studies. Eligible studies were
      randomized controlled trials that reported mortality rates on the use of
      vasopressors and inotropes in patients with septic shock. We chose to use 28-day
      mortality as the outcome assessment criterion. RESULTS: Fourteen studies with a
      total of 2811 patients were included in the analysis. Norepinephrine (NE) and NE
      + low-dose vasopressin but not epinephrine (EPI) were associated with
      significantly reduced mortality compared with dopamine. (Odds ratio, 0.80 [95%
      credibility interval, 0.65-0.99], 0.69 [0.48-0.98], and 0.56 [0.26-1.18],
      respectively). The addition of an inotropic agent such as dobutamine or
      dopexamine did not reduce mortality compared with EPI or NE alone. CONCLUSIONS:
      Our results support the use of NE with or without low-dose vasopressin as the
      first-line vasopressor therapy in septic shock. No concrete evidence exists to
      support the use of EPI over dopamine as the second-line agent or the addition of
      an inotropic agent.

PMID- 24857642
TI  - Limited echocardiography-guided therapy in subacute shock is associated with
      change in management and improved outcomes.
AB  - PURPOSE: The purpose of the study was to compare the effect of limited
      echocardiography (LE)-guided therapy to standard management on 28-day mortality,
      intravenous fluid prescription, and inotropic dosing following early
      resuscitation for shock. MATERIALS AND METHODS: Two hundred twenty critically ill
      patients with undifferentiated shock from a quaternary intensive care unit were
      included in the study. The LE group consisted of 110 consecutive patients
      prospectively studied over a 12-month period receiving LE-guided management. The
      standard management group consisted of 110 consecutive patients retrospectively
      studied with shock immediately prior to the LE intervention. RESULTS: In the LE
      group, fluid restriction was recommended in 71 (65%) patients and initiation of
      dobutamine in 27 (25%). Fluid prescription during the first 24 hours was
      significantly lower in LE patients (49 [33-74] vs 66 [42-100] mL/kg, P = .01),
      whereas 55% more LE patients received dobutamine (22% vs 12%, P = .01). The LE
      patients had improved 28-day survival (66% vs 56%, P = .04), a reduction in stage
      3 acute kidney injury (20% vs 39%), and more days alive and free of renal support
      (28 [9.7-28] vs 25 [5-28], P = .04). CONCLUSIONS: Limited echocardiography-guided
      management following early resuscitation is associated with improved survival,
      less fluid, and increased inotropic prescription. A prospective randomized
      control trial is required to verify these results.

PMID- 24857644
TI  - Phenotyping of leukocytes and granulocyte and monocyte phagocytic activity in the
      peripheral blood and uterus of cows with endometritis.
AB  - This study was a comparative evaluation of selected immunological parameters in
      peripheral blood and uterine wash samples from cows with a normal postpartum
      period compared with cows with endometritis. We aimed to determine the usefulness
      of these parameters in monitoring the puerperium. In total, 40 cows were included
      in the study: 20 had endometritis (experimental group), and 20 did not have
      uterine inflammation (control group). Animals were chosen on the basis of
      cytological and bacteriological test results. The tests were conducted 5, 22, and
      40 days postpartum. In both groups, flow cytometric analysis of the surface
      molecules CD4, CD8, CD21, CD25, and CD14 in the peripheral blood and uterine
      washings was performed. Granulocyte and monocyte phagocytic activity was
      determined using a commercial Phagotest kit that was adapted for flow cytometry.
      The percentage of phagocytic granulocytes and monocytes in both the peripheral
      blood and the uterine washings was significantly lower for cows in the
      experimental group compared with the control group (P < 0.01). A significant
      decrease (P < 0.01) in the percentage of CD4+, CD25+, CD14+, and CD4 + CD25(high)
      leukocyte subpopulations was also observed in the peripheral blood of cows with
      endometritis. A significant decrease (P < 0.01) in CD21+ lymphocytes and an
      increase in CD8+ lymphocytes was detected in uterine washings. The results of
      this work indicate that cell immunity dysfunction may be the main factor causing
      advanced inflammation of the uterus in endometritis. Knowledge of the
      immunological mechanisms observed in cows with endometritis might aid in choosing
      the correct immunomodulating agent-based adjuvant therapy.

PMID- 24857645
TI  - Amyloidosis in the bladder: three cases with different appearance.
AB  - Amyloidosis refers to a number of diseases characterized by extracellular
      deposition of misfolded proteins, called amyloid fibrils, in the tissues and
      organs of the body. Amyloidosis in the bladder is a generally localized, rare
      condition, with approximately 200 cases reported in the literature. This report
      presents three cases of amyloidosis in the bladder, two of which had coexisting
      transitional cell carcinoma. Evaluation for systemic disease is recommended in
      patients with newly discovered amyloidosis, even if first recognized in an area
      with the localized form, as in the bladder.

PMID- 24857646
TI  - Prevention of kidney stones: a call for more evidence-based research.

PMID- 24857647
TI  - AUA guideline on the diagnosis and treatment of cryptorchidism.

PMID- 24857648
TI  - Medical management of kidney stones: AUA guideline.
AB  - PURPOSE: The purpose of this guideline is to provide a clinical framework for the
      diagnosis, prevention and follow-up of adult patients with kidney stones based on
      the best available published literature. MATERIALS AND METHODS: The primary
      source of evidence for this guideline was the systematic review conducted by the
      Agency for Healthcare Research and Quality on recurrent nephrolithiasis in
      adults. To augment and broaden the body of evidence in the AHRQ report, the AUA
      conducted supplementary searches for articles published from 2007 through 2012
      that were systematically reviewed using a methodology developed a priori. In
      total, these sources yielded 46 studies that were used to form evidence-based
      guideline statements. In the absence of sufficient evidence, additional
      statements were developed as Clinical Principles and Expert Opinions. RESULTS:
      Guideline statements were created to inform clinicians regarding the use of a
      screening evaluation for first-time and recurrent stone formers, the appropriate
      initiation of a metabolic evaluation in select patients and recommendations for
      the initiation and follow-up of medication and/or dietary measures in specific
      patients. CONCLUSIONS: A variety of medications and dietary measures have been
      evaluated with greater or less rigor for their efficacy in reducing recurrence
      rates in stone formers. The guideline statements offered in this document provide
      a simple, evidence-based approach to identify high-risk or interested stone
      forming patients for whom medical and dietary therapy based on metabolic testing
      and close follow-up is likely to be effective in reducing stone recurrence.

PMID- 24857649
TI  - Urotrauma guidelines.

PMID- 24857650
TI  - Evaluation and treatment of cryptorchidism: AUA guideline.
AB  - PURPOSE: Cryptorchidism is one of the most common pediatric disorders of the male
      endocrine glands and the most common genital disorder identified at birth. This
      guideline is intended to provide physicians and non-physician providers (primary
      care and specialists) with a consensus of principles and treatment plans for the
      management of cryptorchidism (typically isolated non-syndromic). MATERIALS AND
      METHODS: A systematic review and meta-analysis of the published literature was
      conducted using controlled vocabulary supplemented with key words relating to the
      relevant concepts of cryptorchidism. The search strategy was developed and
      executed by reference librarians and methodologists to create an evidence report
      limited to English-language, published peer-reviewed literature. This review
      yielded 704 articles published from 1980 through 2013 that were used to form a
      majority of the guideline statements. Clinical Principles and Expert Opinions
      were used for guideline statements lacking sufficient evidence-based data.
      RESULTS: Guideline statements were created to inform clinicians on the proper
      methods of history-taking, physical exam, and evaluation of the boy with
      cryptorchidism, as well as the various hormonal and surgical treatment options.
      CONCLUSIONS: Imaging for cryptorchidism is not recommended prior to referral,
      which should occur by 6 months of age. Orchidopexy (orchiopexy is the preferred
      term) is the most successful therapy to relocate the testis into the scrotum,
      while hormonal therapy is not recommended. Successful scrotal repositioning of
      the testis may reduce but does not prevent the potential long-term issues of
      infertility and testis cancer. Appropriate counseling and follow-up of the
      patient is essential.

PMID- 24857652
TI  - Transcription factor cooperativity in early adipogenic hotspots and super
      enhancers.
AB  - It is becoming increasingly clear that transcription factors operate in complex
      networks through thousands of genomic binding sites, many of which bind several
      transcription factors. However, the extent and mechanisms of crosstalk between
      transcription factors at these hotspots remain unclear. Using a combination of
      advanced proteomics and genomics approaches, we identify ~12,000 transcription
      factor hotspots (~400 bp) in the early phase of adipogenesis, and we find
      evidence of both simultaneous and sequential binding of transcription factors at
      these regions. We demonstrate that hotspots are highly enriched in large super
      enhancer regions (several kilobases), which drive the early adipogenic
      reprogramming of gene expression. Our results indicate that cooperativity between
      transcription factors at the level of hotspots as well as super-enhancers is very
      important for enhancer activity and transcriptional reprogramming. Thus, hotspots
      and super-enhancers constitute important regulatory hubs that serve to integrate
      external stimuli on chromatin. 

PMID- 24857653
TI  - Selective activation of mTORC1 signaling recapitulates microcephaly, tuberous
      sclerosis, and neurodegenerative diseases.
AB  - Mammalian target of rapamycin (mTOR) has been implicated in human neurological
      diseases such as tuberous sclerosis complex (TSC), neurodegeneration, and autism.
      However, little is known about when and how mTOR is involved in the pathogenesis
      of these diseases, due to a lack of animal models that directly increase mTOR
      activity. Here, we generated transgenic mice expressing a gain-of-function mutant
      of mTOR in the forebrain in a temporally controlled manner. Selective activation
      of mTORC1 in embryonic stages induced cortical atrophy caused by prominent
      apoptosis of neuronal progenitors, associated with upregulation of HIF-1alpha. In
      striking contrast, activation of the mTORC1 pathway in adulthood resulted in
      cortical hypertrophy with fatal epileptic seizures, recapitulating human TSC.
      Activated mTORC1 in the adult cortex also promoted rapid accumulation of
      cytoplasmic inclusions and activation of microglial cells, indicative of
      progressive neurodegeneration. Our findings demonstrate that mTORC1 plays
      different roles in developmental and adult stages and contributes to human
      neurological diseases. 

PMID- 24857651
TI  - Urotrauma: AUA guideline.
AB  - PURPOSE: The authors of this guideline reviewed the urologic trauma literature to
      guide clinicians in the appropriate methods of evaluation and management of
      genitourinary injuries. MATERIALS AND METHODS: A systematic review of the
      literature using the MEDLINE(r) and EMBASE databases (search dates 1/1/90
      9/19/12) was conducted to identify peer-reviewed publications relevant to
      urotrauma. The review yielded an evidence base of 372 studies after application
      of inclusion/exclusion criteria. These publications were used to inform the
      statements presented in the guideline as Standards, Recommendations or Options.
      When sufficient evidence existed, the body of evidence for a particular treatment
      was assigned a strength rating of A (high), B (moderate) or C (low). In the
      absence of sufficient evidence, additional information is provided as Clinical
      Principles and Expert Opinions. RESULTS: Guideline statements were created to
      inform clinicians on the initial observation, evaluation and subsequent
      management of renal, ureteral, bladder, urethral and genital traumatic injuries.
      CONCLUSIONS: Genitourinary organ salvage has become increasingly possible as a
      result of advances in imaging, minimally invasive techniques, and reconstructive
      surgery. As the field of genitourinary reconstruction continues to evolve,
      clinicians must strive to approach clinical problems in a creative,
      multidisciplinary, evidence-based manner to ensure optimal outcomes.

PMID- 24857655
TI  - Reversible 26S proteasome disassembly upon mitochondrial stress.
AB  - In eukaryotic cells, proteasomes exist primarily as 26S holoenzymes, the most
      efficient configuration for ubiquitinated protein degradation. Here, we show that
      acute oxidative stress caused by environmental insults or mitochondrial defects
      results in rapid disassembly of 26S proteasomes into intact 20S core and 19S
      regulatory particles. Consequently, polyubiquitinated substrates accumulate,
      mitochondrial networks fragment, and cellular reactive oxygen species (ROS)
      levels increase. Oxidation of cysteine residues is sufficient to induce
      proteasome disassembly, and spontaneous reassembly from existing components is
      observed both in vivo and in vitro upon reduction. Ubiquitin-dependent substrate
      turnover also resumes after treatment with antioxidants. Reversible attenuation
      of 26S proteasome activity induced by acute mitochondrial or oxidative stress may
      be a short-term response distinct from adaptation to long-term ROS exposure or
      changes during aging. 

PMID- 24857654
TI  - A role for dendritic mGluR5-mediated local translation of Arc/Arg3.1 in MEF2
      dependent synapse elimination.
AB  - Experience refines synaptic connectivity through neural activity-dependent
      regulation of transcription factors. Although activity-dependent regulation of
      transcription factors has been well described, it is unknown whether synaptic
      activity and local, dendritic regulation of the induced transcripts are necessary
      for mammalian synaptic plasticity in response to transcription factor activation.
      Neuronal depolarization activates the myocyte enhancer factor 2 (MEF2) family of
      transcription factors that suppresses excitatory synapse number. We report that
      activation of metabotropic glutamate receptor 5 (mGluR5) on the dendrites, but
      not cell soma, of hippocampal CA1 neurons is required for MEF2-induced functional
      and structural synapse elimination. We present evidence that mGluR5 is necessary
      for synapse elimination to stimulate dendritic translation of the MEF2 target
      gene Arc/Arg3.1. Activity-regulated cytoskeletal-associated protein (Arc) is
      required for MEF2-induced synapse elimination, where it plays an acute, cell
      autonomous, and postsynaptic role. This work reveals a role for dendritic
      activity in local translation of specific transcripts in synapse refinement. 

PMID- 24857656
TI  - PER1 phosphorylation specifies feeding rhythm in mice.
AB  - Organization of circadian behavior, physiology, and metabolism is important for
      human health. An S662G mutation in hPER2 has been linked to familial advanced
      sleep-phase syndrome (FASPS). Although the paralogous phosphorylation site S714
      in PER1 is conserved in mice, its specific function in circadian organization
      remains unknown. Here, we find that the PER1S714G mutation accelerates the
      molecular feedback loop. Furthermore, hPER1S714G mice, but not hPER2S662G mice,
      exhibit peak time of food intake that is several hours before daily energy
      expenditure peaks. Both the advanced feeding behavior and the accelerated clock
      disrupt the phase of expression of several key metabolic regulators in the liver
      and adipose tissue. Consequently, hPER1S714G mice rapidly develop obesity on a
      high-fat diet. Our studies demonstrate that PER1 and PER2 are linked to different
      downstream pathways and that PER1 maintains coherence between the circadian clock
      and energy metabolism.

PMID- 24857657
TI  - HuD regulates coding and noncoding RNA to induce APP->Abeta processing.
AB  - The primarily neuronal RNA-binding protein HuD is implicated in learning and
      memory. Here, we report the identification of several HuD target transcripts
      linked to Alzheimer's disease (AD) pathogenesis. HuD interacted with the 3' UTRs
      of APP mRNA (encoding amyloid precursor protein) and BACE1 mRNA (encoding beta
      site APP-cleaving enzyme 1) and increased the half-lives of these mRNAs. HuD also
      associated with and stabilized the long noncoding (lnc)RNA BACE1AS, which partly
      complements BACE1 mRNA and enhances BACE1 expression. Consistent with HuD
      promoting production of APP and APP-cleaving enzyme, the levels of APP, BACE1,
      BACE1AS, and Abeta were higher in the brain of HuD-overexpressing mice.
      Importantly, cortex (superior temporal gyrus) from patients with AD displayed
      significantly higher levels of HuD and, accordingly, elevated APP, BACE1,
      BACE1AS, and Abeta than did cortical tissue from healthy age-matched individuals.
      We propose that HuD jointly promotes the production of APP and the cleavage of
      its amyloidogenic fragment, Abeta. 

PMID- 24857658
TI  - Oxidation of alpha-ketoglutarate is required for reductive carboxylation in
      cancer cells with mitochondrial defects.
AB  - Mammalian cells generate citrate by decarboxylating pyruvate in the mitochondria
      to supply the tricarboxylic acid (TCA) cycle. In contrast, hypoxia and other
      impairments of mitochondrial function induce an alternative pathway that produces
      citrate by reductively carboxylating alpha-ketoglutarate (AKG) via NADPH
      dependent isocitrate dehydrogenase (IDH). It is unknown how cells generate
      reducing equivalents necessary to supply reductive carboxylation in the setting
      of mitochondrial impairment. Here, we identified shared metabolic features in
      cells using reductive carboxylation. Paradoxically, reductive carboxylation was
      accompanied by concomitant AKG oxidation in the TCA cycle. Inhibiting AKG
      oxidation decreased reducing equivalent availability and suppressed reductive
      carboxylation. Interrupting transfer of reducing equivalents from NADH to NADPH
      by nicotinamide nucleotide transhydrogenase increased NADH abundance and
      decreased NADPH abundance while suppressing reductive carboxylation. The data
      demonstrate that reductive carboxylation requires bidirectional AKG metabolism
      along oxidative and reductive pathways, with the oxidative pathway producing
      reducing equivalents used to operate IDH in reverse. 

PMID- 24857659
TI  - Impact of regulated secretion on antiparasitic CD8 T cell responses.
AB  - CD8 T cells play a key role in defense against the intracellular parasite
      Toxoplasma, but why certain CD8 responses are more potent than others is not well
      understood. Here, we describe a parasite antigen, ROP5, that elicits a CD8 T cell
      response in genetically susceptible mice. ROP5 is secreted via parasite
      organelles termed rhoptries that are injected directly into host cells during
      invasion, whereas the protective, dense-granule antigen GRA6 is constitutively
      secreted into the parasitophorous vacuole. Transgenic parasites in which the ROP5
      antigenic epitope was targeted for secretion through dense granules led to
      enhanced CD8 T cell responses, whereas targeting the GRA6 epitope to rhoptries
      led to reduced CD8 responses. CD8 T cell responses to the dense-granule-targeted
      ROP5 epitope resulted in reduced parasite load in the brain. These data suggest
      that the mode of secretion affects the efficacy of parasite-specific CD8 T cell
      responses. 

PMID- 24857661
TI  - LIF mediates proinvasive activation of stromal fibroblasts in cancer.
AB  - Signaling crosstalk between tumor cells and fibroblasts confers proinvasive
      properties to the tumor microenvironment. Here, we identify leukemia inhibitory
      factor (LIF) as a tumor promoter that mediates proinvasive activation of stromal
      fibroblasts independent of alpha-smooth muscle actin (alpha-SMA) expression. We
      demonstrate that a pulse of transforming growth factor beta (TGF-beta)
      establishes stable proinvasive fibroblast activation by inducing LIF production
      in both fibroblasts and tumor cells. In fibroblasts, LIF mediates TGF-beta
      dependent actomyosin contractility and extracellular matrix remodeling, which
      results in collective carcinoma cell invasion in vitro and in vivo. Accordingly,
      carcinomas from multiple origins and melanomas display strong LIF upregulation,
      which correlates with dense collagen fiber organization, cancer cell collective
      invasion, and poor clinical outcome. Blockade of JAK activity by Ruxolitinib (JAK
      inhibitor) counteracts fibroblast-dependent carcinoma cell invasion in vitro and
      in vivo. These findings establish LIF as a proinvasive fibroblast producer
      independent of alpha-SMA and may open novel therapeutic perspectives for patients
      with aggressive primary tumors. 

PMID- 24857660
TI  - Targeting polycomb to pericentric heterochromatin in embryonic stem cells reveals
      a role for H2AK119u1 in PRC2 recruitment.
AB  - The mechanisms by which the major Polycomb group (PcG) complexes PRC1 and PRC2
      are recruited to target sites in vertebrate cells are not well understood.
      Building on recent studies that determined a reciprocal relationship between DNA
      methylation and Polycomb activity, we demonstrate that, in methylation-deficient
      embryonic stem cells (ESCs), CpG density combined with antagonistic effects of
      H3K9me3 and H3K36me3 redirects PcG complexes to pericentric heterochromatin and
      gene-rich domains. Surprisingly, we find that PRC1-linked H2A monoubiquitylation
      is sufficient to recruit PRC2 to chromatin in vivo, suggesting a mechanism
      through which recognition of unmethylated CpG determines the localization of both
      PRC1 and PRC2 at canonical and atypical target sites. We discuss our data in
      light of emerging evidence suggesting that PcG recruitment is a default state at
      licensed chromatin sites, mediated by interplay between CpG hypomethylation and
      counteracting H3 tail modifications. 

PMID- 24857662
TI  - Inhibition of endothelial p53 improves metabolic abnormalities related to dietary
      obesity.
AB  - Accumulating evidence has suggested a role for p53 activation in various age
      associated conditions. Here, we identified a crucial role of endothelial p53
      activation in the regulation of glucose homeostasis. Endothelial expression of
      p53 was markedly upregulated when mice were fed a high-calorie diet. Disruption
      of endothelial p53 activation improved dietary inactivation of endothelial nitric
      oxide synthase that upregulated the expression of peroxisome proliferator
      activated receptor-gamma coactivator-1alpha in skeletal muscle, thereby
      increasing mitochondrial biogenesis and oxygen consumption. Mice with endothelial
      cell-specific p53 deficiency fed a high-calorie diet showed improvement of
      insulin sensitivity and less fat accumulation, compared with control littermates.
      Conversely, upregulation of endothelial p53 caused metabolic abnormalities. These
      results indicate that inhibition of endothelial p53 could be a novel therapeutic
      target to block the vicious cycle of cardiovascular and metabolic abnormalities
      associated with obesity. 

PMID- 24857663
TI  - The CD3 conformational change in the gammadelta T cell receptor is not triggered
      by antigens but can be enforced to enhance tumor killing.
AB  - Activation of the T cell receptor (TCR) by antigen is the key step in adaptive
      immunity. In the alphabetaTCR, antigen induces a conformational change at the CD3
      subunits (CD3 CC) that is absolutely required for alphabetaTCR activation. Here,
      we demonstrate that the CD3 CC is not induced by antigen stimulation of the mouse
      G8 or the human Vgamma9Vdelta2 gammadeltaTCR. We find that there is a fundamental
      difference between the activation mechanisms of the alphabetaTCR and
      gammadeltaTCR that map to the constant regions of the TCRalphabeta/gammadelta
      heterodimers. Enforced induction of CD3 CC with a less commonly used monoclonal
      anti-CD3 promoted proximal gammadeltaTCR signaling but inhibited cytokine
      secretion. Utilizing this knowledge, we could dramatically improve in vitro tumor
      cell lysis by activated human gammadelta T cells. Thus, manipulation of the CD3
      CC might be exploited to improve clinical gammadelta T cell-based
      immunotherapies. 

PMID- 24857664
TI  - Widespread inhibition of posttranscriptional splicing shapes the cellular
      transcriptome following heat shock.
AB  - During heat shock and other proteotoxic stresses, cells regulate multiple steps
      in gene expression in order to globally repress protein synthesis and selectively
      upregulate stress response proteins. Splicing of several mRNAs is known to be
      inhibited during heat stress, often meditated by SRp38, but the extent and
      specificity of this effect have remained unclear. Here, we examined splicing
      regulation genome-wide during heat shock in mouse fibroblasts. We observed
      widespread retention of introns in transcripts from ~1,700 genes, which were
      enriched for tRNA synthetase, nuclear pore, and spliceosome functions.
      Transcripts with retained introns were largely nuclear and untranslated. However,
      a group of 580+ genes biased for oxidation reduction and protein folding
      functions continued to be efficiently spliced. Interestingly, these unaffected
      transcripts are mostly cotranscriptionally spliced under both normal and stress
      conditions, whereas splicing-inhibited transcripts are mostly spliced
      posttranscriptionally. Altogether, our data demonstrate widespread repression of
      splicing in the mammalian heat stress response, disproportionately affecting
      posttranscriptionally spliced genes. 

PMID- 24857666
TI  - Molecular architecture of transcription factor hotspots in early adipogenesis.
AB  - Transcription factors have recently been shown to colocalize in hotspot regions
      of the genome, which are further clustered into super-enhancers. However, the
      detailed molecular organization of transcription factors at hotspot regions is
      poorly defined. Here, we have used digital genomic footprinting to precisely
      define factor localization at a genome-wide level during the early phase of 3T3
      L1 adipocyte differentiation, which allows us to obtain detailed molecular
      insight into how transcription factors target hotspots. We demonstrate the
      formation of ATF-C/EBP heterodimers at a composite motif on chromatin, and we
      suggest that this may be a general mechanism for integrating external signals on
      chromatin. Furthermore, we find evidence of extensive recruitment of
      transcription factors to hotspots through alternative mechanisms not involving
      their known motifs and demonstrate that these alternative binding events are
      functionally important for hotspot formation and activity. Taken together, these
      findings provide a framework for understanding transcription factor cooperativity
      in hotspots. 

PMID- 24857665
TI  - Optogenetic mapping of cerebellar inhibitory circuitry reveals spatially biased
      coordination of interneurons via electrical synapses.
AB  - We used high-speed optogenetic mapping technology to examine the spatial
      organization of local inhibitory circuits formed by cerebellar interneurons.
      Transgenic mice expressing channelrhodopsin-2 exclusively in molecular layer
      interneurons allowed us to focally photostimulate these neurons, while measuring
      resulting responses in postsynaptic Purkinje cells. This approach revealed that
      interneurons converge upon Purkinje cells over a broad area and that at least
      seven interneurons form functional synapses with a single Purkinje cell. The
      number of converging interneurons was reduced by treatment with gap junction
      blockers, revealing that electrical synapses between interneurons contribute
      substantially to the spatial convergence. Remarkably, gap junction blockers
      affected convergence in sagittal slices, but not in coronal slices, indicating a
      sagittal bias in electrical coupling between interneurons. We conclude that
      electrical synapse networks spatially coordinate interneurons in the cerebellum
      and may also serve this function in other brain regions. 

PMID- 24857667
TI  - Fatal monkeypox in wild-living sooty mangabey, Cote d'Ivoire, 2012.
AB  - We isolated a monkeypox virus from a wild-living monkey, a sooty mangabey, found
      dead in Tai National Park, Cote d'Ivoire, in March 2012. The whole-genome
      sequence obtained from this isolate and directly from clinical specimens showed
      its close relationship to monkeypox viruses from Western Africa. 

PMID- 24857672
TI  - Investigational therapies for the treatment of atherosclerosis.
AB  - INTRODUCTION: There is great need for new drugs to reduce cholesterol in those
      patients who have not achieved target levels on statins as well as those who are
      statin intolerant. AREAS COVERED: In this review, the authors discuss the new
      antisense oligotide inhibitor of apo B synthesis, mipomersen; pro-protein
      convertase subtilisin/kexin type 9 (PCSK9) inhibitors and cholesterol ester
      transport protein (CETP) inhibitors. Furthermore, the authors discuss cholesterol
      absorption and chylomicron synthesis with an emphasis on microsomal triglyceride
      transfer protein (MTP) inhibitors, which inhibit very-low-density lipoprotein
      production in the liver and chylomicron inhibition in the intestine. Finally, the
      authors also discuss Apo A1- and adenosine triphosphate-binding cassette
      transporter A1 (ABCA1)-promoting drugs. A literature review was performed through
      PubMed using the terms atherosclerosis, hypercholesterolemia, Apo B inhibition,
      PSCK9, CETP inhibitors, MTP inhibitors, apo A1 mimetics and ABCA1. EXPERT
      OPINION: So far, research suggests that PCSK9 inhibitors will be successful with
      mipomersen being used for those patients who do not respond well or who are still
      not at target. However, it is difficult to see where CETP inhibitors will fit in
      except with patients who have very low high-density lipoprotein. The MTP
      inhibitor lomitapide is currently only licensed for familial homozygous
      hypercholesterolemia but the intestinal inhibitors may have a future,
      particularly in familial combined hyperlipidemia. The future will be most
      exciting.

PMID- 24857674
TI  - Healthy eating on a budget at ChooseMyPlate.gov.

PMID- 24857675
TI  - Are there guidelines to evaluate claims made for weight-loss products?

PMID- 24857676
TI  - Expected and unexpected imaging features after oesophageal cancer treatment.
AB  - Oesophageal cancer is a leading cause of cancer-related mortality worldwide.
      Various surgical procedures are performed for oesophageal malignancies. The
      advancement in surgical technique as well as post-surgical care has significantly
      reduced the complication rate. However, various complications may still occur
      either immediately (infection, aspiration, anastomotic leak, ischaemic necrosis,
      fistulae, chylothorax) or late after surgery (strictures, tumour recurrence,
      fistulae, delayed emptying). The palliative treatment options of radiotherapy and
      stent placement may also be accompanied by complications, such as radiation
      necrosis, stricture, and stent ingrowth by the tumour. This review presents the
      expected post-surgical appearance as well as various complications after surgical
      and non-surgical treatments of oesophageal cancer.

PMID- 24857677
TI  - Revisiting the relationship between tumour volume and diameter in advanced NSCLC
      patients: An exercise to maximize the utility of each measure to assess response
      to therapy.
AB  - AIM: To revisit the presumed relationship between tumour diameter and volume in
      advanced non-small-cell lung cancer (NSCLC) patients, and determine whether the
      measured volume using volume-analysis software and its proportional changes
      during therapy matches with the calculated volume obtained from the presumed
      relationship and results in concordant response assessment. MATERIALS AND
      METHODS: Twenty-three patients with stage IIIB/IV NSCLC with a total of 53
      measurable lung lesions, treated in a phase II trial of erlotinib, were studied
      with institutional review board approval. Tumour volume and diameter were
      measured at baseline and at the first follow-up computed tomography (CT)
      examination using volume-analysis software. Using the measured diameter (2r) and
      the equation, calculated volume was obtained as (4/3)pir(3) at baseline and at
      the follow-up. Percent volume change was obtained by comparing to baseline for
      measured and calculated volumes, and response assessment was assigned. RESULTS:
      The measured volume was significantly smaller than the calculated volume at
      baseline (median 11,488.9 mm(3) versus 17,148.6 mm(3); p < 0.0001), with a
      concordance correlation coefficient (CCC) of 0.7022. At follow-up, the measured
      volume was once again significantly smaller than the calculated volume (median
      6573.5 mm(3) versus 9198.1 mm(3); p = 0.0022), with a CCC of 0.7408. Response
      assessment by calculated versus measured volume changes had only moderate
      agreement (weighted kappa = 0.545), with discordant assessment results in 20%
      (8/40) of lesions. CONCLUSION: Calculated volume based on the presumed
      relationship significantly differed from the measured volume in advanced NSCLC
      patients, with only moderate concordance in response assessment, indicating the
      limitations of presumed relationship.

PMID- 24857678
TI  - Vitrification preserves murine and human donor cells for generation of tissue
      engineered intestine.
AB  - BACKGROUND: Short bowel syndrome causes significant morbidity and mortality.
      Tissue-engineered intestine may serve as a viable replacement. Tissue-engineered
      small intestine (TESI) has previously been generated in the mouse model from
      donor cells that were harvested and immediately reimplanted; however, this
      technique may prove impossible in children who are critically ill,
      hemodynamically unstable, or septic. We hypothesized that organoid units (OU),
      multicellular clusters containing epithelium and mesenchyme, could be
      cryopreserved for delayed production of TESI. METHODS: OU were isolated from <3
      wk-old mouse or human ileum. OU were then cryopreserved by either standard snap
      freezing or vitrification. In the snap freezing protocol, OU were suspended in
      cryoprotectant and transferred directly to -80 degrees C for storage. The
      vitrification protocol began with a stepwise increase in cryoprotectant
      concentration followed by liquid supercooling of the OU solution to -13 degrees C
      and nucleation with a metal rod to induce vitrification. Samples were then cooled
      to -80 degrees C at a controlled rate of -1 degrees C/min and subsequently
      plunged into liquid nitrogen for long-term storage. OU from both groups were
      maintained in cryostorage for at least 72 h and thawed in a 37 degrees C water
      bath. Cryoprotectant was removed with serial sucrose dilutions and OU were
      assessed by Trypan blue assay for post-cryopreservation viability. Via techniques
      previously described by our laboratory, the thawed murine or human OU were either
      cultured in vitro or implanted on a scaffold into the omentum of a syngeneic or
      irradiated Nonobese Diabetic/Severe Combined Immunodeficiency, gamma chain
      deficient adult mouse. The resultant TESI was analyzed by histology and
      immunofluorescence. RESULTS: After cryopreservation, the viability of murine OU
      was significantly higher in the vitrification group (93 +/- 2%, mean +/- standard
      error of the mean) compared with standard freezing (56 +/- 6%) (P < 0.001,
      unpaired t-test, n = 25). Human OU demonstrated similar viability after
      vitrification (89 +/- 2%). In vitro culture of thawed OU produced expanding
      epithelial spheres supported by a layer of mesenchyme. TESI was successfully
      generated from the preserved OU. Hematoxylin and eosin staining demonstrated a
      mucosa composed of a simple columnar epithelium whereas immunofluorescence
      staining confirmed the presence of both progenitor and differentiated epithelial
      cells. Furthermore, beta-2-microglobulin confirmed that the human TESI epithelium
      originated from human cells. CONCLUSIONS: We demonstrated improved multicellular
      viability after vitrification over conventional cryopreservation techniques and
      the first successful vitrification of murine and human OU with subsequent TESI
      generation. Clinical application of this method may allow for delayed autologous
      implantation of TESI for children in extremis.

PMID- 24857680
TI  - Coiled coil peptides and polymer-peptide conjugates: synthesis, self-assembly,
      characterization and potential in drug delivery systems.
AB  - Coiled coils are a common structural motif in many natural proteins that can also
      be utilized in the design and preparation of drug delivery systems for the
      noncovalent connection of two macromolecules. In this work, two different pairs
      of peptides forming coiled coil hetero-oligomers were designed, synthesized, and
      characterized. While the peptide sequences (VAALEKE)4 and (VAALKEK)4
      predominantly form coiled coil heterodimers with randomly orientated peptide
      chains, (IAALESE)2-IAALESKIAALESE and IAALKSKIAALKSE-(IAALKSK)2 tend to form
      higher hetero-oligomers with an antiparallel orientation of their peptide chains.
      The associative behavior of these peptides was studied in aqueous solutions using
      circular dichroism spectroscopy, size-exclusion chromatography, isothermal
      titration calorimetry and sedimentation analyses. The orientation of the peptide
      chains in the coiled coil heterodimers was assessed using fluorescence
      spectroscopy with fluorescence resonance energy transfer labels attached to the
      ends of the peptides. The formation of the heterodimer can be used as a general
      method for the selective noncovalent conjugation of a specific targeting moiety
      with various drug carrier systems; this process involves simple self-assembly in
      a physiological solution before drug administration. The preparation of targeted
      macromolecular therapeutics consisting of a synthetic polymer drug carrier and a
      recombinant protein targeting ligand is discussed. 

PMID- 24857681
TI  - Human granulocytic anaplasmosis acquired in Scotland, 2013.

PMID- 24857682
TI  - Filling the voids of graphene foam with graphene "eggshell" for improved lithium
      ion storage.
AB  - Highly porous, N-doped graphene foam is synthesized by chemical vapor deposition
      process on nickel foam. The voids of the graphene foam can be filled with curved
      graphene sheets by impregnating the nickel foam template with micrometer-sized
      nickel powder. Subsequent etching of nickel produces a graphene "eggshells"-in
      graphene foam structure. The reversible capacity of such graphene foam when used
      as anode in lithium ion battery is improved by the presence of graphene
      "eggshells", as compared to the unfilled foam. The improvement is attributed to
      the higher rate of lithium diffusion, better buffering of strain associated with
      lithiation/delithiation and higher volumetric energy density of the unique
      eggshell-in-graphene foam structure. 

PMID- 24857683
TI  - Coupling between high-frequency ultrasound and solar photo-Fenton at pilot scale
      for the treatment of organic contaminants: an initial approach.
AB  - This study aims to evaluate the performance of a novel pilot-scale coupled system
      consisting of a high frequency ultrasonic reactor (400kHz) and a compound
      parabolic collector (CPC). The benefits of the concurrent application of
      ultrasound and the photo-Fenton process were studied in regard to the degradation
      behavior of a series of organic pollutants. Three compounds (phenol, bisphenol A
      and diuron) with different physicochemical properties have been chosen in order
      to identify possible synergistic effects and to obtain a better estimate of the
      general feasibility of such a system at field scale (10L). Bisphenol A and diuron
      were specifically chosen due to their high hydrophobicity, and thus their assumed
      higher affinity towards the cavitation bubble. Experiments were conducted under
      ultrasonic, photo-Fenton and combined treatments. Enhanced degradation kinetics
      were observed during the coupled treatment and synergy factors clearly in excess
      of 1 have been calculated for phenol as well as for saturated solutions of
      bisphenol A and diuron. Although the relatively high cost of ultrasound compared
      to photo-Fenton still presents a significant challenge towards mainstream
      industrial application, the observed behavior suggests that its prudent use has
      the potential to significantly benefit the photo-Fenton process, via the decrease
      of both treatment time and H2O2 consumption. 

PMID- 24857684
TI  - Sonochemical-assisted synthesis of 3D graphene/nanoparticle foams and their
      application in supercapacitor.
AB  - Graphene and its derivatives have attracted much attention in application of
      electrochemical devices. Construction of three-dimensional (3D) heterostructured
      composites is promising for establishing high-performance devices, which enables
      large surface area, facilitated ion and electron transport, and synergistic
      effects between multicomponents. Here, we report a simple and general
      sonochemical-assisted synthesis to prepare various 3D porous
      graphene/nanoparticle (i.e., Pt, Au, Pd, Ru, and MnO2) foams using colloidal
      template. The 3D porous network structure of composite foams significantly
      improves a large surface area of around 550m(2)g(-1) compared to the bare
      graphene (215m(2)g(-1)). This unique structure of 3D graphene/MnO2 enables
      further improvement of electrochemical characteristics, compared with bare
      graphene/MnO2 composite, showing a high specific capacitance of 421Fg(-1) at
      0.1Ag(-1), high rate capability (97% retention at 20Ag(-1)), and good cycling
      performance (97% retention over 1000 cycles). Moreover, electrochemical impedance
      analysis demonstrates that electron and ion transfer are triggered by 3D porous
      structure. 

PMID- 24857685
TI  - Pharmacogenetic biomarkers for predicting drug response.
AB  - Drug response shows significant interpatient variability and evidence that
      genetics influences outcome of drug therapy has been known for more than five
      decades. However, the translation of this knowledge to clinical practice remains
      slow. Using examples from clinical practice six considerations about the
      implementation of pharmacogenetics (PGx) into routine care are discussed: the
      need for PGx biomarkers; the sources of genetic variability in drug response; the
      amount of variability explained by PGx; whether PGx test results are actionable;
      the level of evidence needed for implementation of PGx and the sources of
      information regarding interpretation of PGx data. 

PMID- 24857686
TI  - Discounting of money and sex: effects of commodity and temporal position in
      stimulant-dependent men and women.
AB  - Research on delay discounting has contributed to the understanding of numerous
      addiction-related phenomena. For example, studies have shown that substance
      dependent individuals discount their addictive substances (e.g., cocaine) more
      rapidly than they do other commodities (e.g., money). Recent research has shown
      that substance dependent individuals discount delayed sex more rapidly than
      delayed money, and their discounting rates for delayed sex were higher than those
      of non-addicted individuals. The particular reason that delay discounting rates
      for sex are higher than those for money, however, are unclear. Do individuals
      discount delayed sex rapidly because immediate sex is particularly appealing or
      because delayed sex does not retain its value? Moreover, do the same factors
      influence men and women's choices? The current study examined delay discounting
      in four conditions (money now versus money later; sex now versus sex later; money
      now, versus sex later; sex now versus money later) in cocaine dependent men and
      women. The procedures used isolated the role of the immediate versus delayed
      commodity. For men, the higher rates of delay discounting for sex were because
      delayed sex did not retain its value, whereas both the immediate and delayed
      commodity influenced the female participants' decisions. 

PMID- 24857687
TI  - Anti-VEGF treatment patterns for neovascular age-related macular degeneration
      among medicare beneficiaries.
AB  - PURPOSE: To examine the use of anti-vascular endothelial growth factor (VEGF)
      therapy in clinical practice among patients with neovascular age-related macular
      degeneration (AMD). DESIGN: Retrospective cohort study. METHODS: Among 459 237
      Medicare beneficiaries, we identified anti-VEGF treatment using claims for
      intravitreal injections of anti-VEGF medications with a supporting diagnosis of
      neovascular AMD. We used the cumulative incidence function to calculate the
      frequency of anti-VEGF treatments and treatment visits for neovascular AMD per
      treated eye in the first and second year after the initial anti-VEGF injection.
      We calculated the mean number of treatments and treatment visits per eye using
      the mean frequency function. Rates of discontinuation were estimated using Kaplan
      Meier methods. RESULTS: The mean number of injections was 4.3 in the first year,
      with 58% of patients receiving 1-4 injections, 20% receiving 5-6 injections, and
      22% receiving 7 or more injections. Among patients who received 7 or more
      injections during the first year, 31% received a comparable number during the
      second year, and 12% received no injections. Of patients who received 1-4
      injections during the first year, 70% received no injections and 24% received 1-4
      injections during the second year. Rates of anti-VEGF discontinuation were 57%
      within 12 months and 71% within 24 months. CONCLUSIONS: The frequency of anti
      VEGF injections for neovascular AMD was lower than that recommended by large
      scale clinical trials, and rates of discontinuation were high. National practice
      patterns in anti-VEGF therapy for patients with neovascular AMD do not reflect
      optimal treatment strategies suggested by recent clinical trial evidence.

PMID- 24857688
TI  - Radial versus raster spectral-domain optical coherence tomography scan patterns
      for detection of macular pathology.
AB  - PURPOSE: To compare the 6-line radial vs the 25-line raster spectral-domain
      optical coherence tomography (SD OCT) acquisition patterns at detecting
      intraretinal fluid, subretinal fluid, vitreomacular traction, and full-thickness
      macular hole (MH). DESIGN: Retrospective cross-sectional analysis. METHODS:
      Series of 365 eyes with neovascular age-related macular degeneration (AMD),
      diabetic macular edema (DME), central and branch retinal vein occlusion
      (CRVO/BRVO), central serous chorioretinopathy, vitreomacular traction, and full
      thickness MH. Sequential 6-line radial and 25-line raster scans were evaluated
      for intraretinal/subretinal fluid and, when applicable, vitreomacular traction
      and MH. RESULTS: For neovascular AMD (133 scans), 7 25-line raster scans
      confirmed subretinal/intraretinal fluid not identified by the 6-line radial
      (P=.02). For DME (140 scans) and central serous chorioretinopathy (91 scans), 25
      line raster confirmed fluid in 4 scans (P=.13) and 1 scan (P=.32), respectively,
      that was not observed with the 6-line radial. For CRVO (123 scans) and BRVO (126
      scans), 25-line raster confirmed fluid on 2 (P=.25) and 4 scans (P=.13),
      respectively, that was not detected by the 6-line radial. Conversely, for focal
      vitreomacular traction (70 scans) and full-thickness MH (82 scans), 25-line
      raster missed focal traction (<1500 MUm) and MH in 5 scans (P=.07) and 7 scans
      (P=.02), respectively, that were identified using the 6-line radial. CONCLUSIONS:
      The 6-line radial scan is statistically comparable to the 25-line raster at
      detecting fluid in DME, BRVO/CRVO, and central serous chorioretinopathy, but not
      neovascular AMD. Furthermore, it is superior to the 25-line raster pattern at
      detecting early MH formation, while demonstrating a positive trend in identifying
      focal vitreomacular traction.

PMID- 24857690
TI  - 5-Year cost/benefit analysis of revision of failed unicompartmental knee
      replacements (UKRs); not "just" a primary total knee replacement (TKR).
AB  - BACKGROUND: A number of studies suggest that one advantage of a unicompartmental
      knee replacement (UKR) is ease of revision to a total knee replacement (TKR). We
      aimed to perform a cost/benefit analysis of patients undergoing this procedure at
      our centre to evaluate its economic viability. METHODS: From our own prospective
      joint replacement database we identified 812 consecutive tibio-femoral UKRs
      performed (1994-2007) of which 23 were revised to TKR (2005-2008). These were
      then matched to a cohort of primary TKRs (42 patients). Data were collected
      regarding patient demographics, cost of surgery, clinical outcome (OKS) and
      follow-up costs at five years. RESULTS: There was no significant difference in
      implant costs or in length of stay, however tourniquet time was significantly
      higher in the revision group (average 93 min (UKR) vs 75 min (TKR) p<0.0001). At
      five years there was no significant difference in clinical outcome between the
      revision UKR and primary TKR groups, mean OKS 27 and 32 respectively (p=0.20).
      The revision group had a greater complication and revision rate, attending
      significantly more follow-up appointments (average 6 (UKR) vs 2 (TKR) p<0.0001)
      and consultant appointments (average 4 (UKR) vs 0.4 (TKR) p<0.0001). This was
      translated to significantly higher follow-up costs. CONCLUSION: Revision of UKR
      to TKR is not universally a straightforward procedure comparable to a standard
      primary replacement. Despite cost of components not being significantly higher
      than primary TKR there are multiple hidden follow-up costs. The clinical outcomes
      are however similar at 5 years.

PMID- 24857689
TI  - Relation between time spent outdoors and exfoliation glaucoma or exfoliation
      glaucoma suspect.
AB  - PURPOSE: To evaluate the relation between time spent outdoors at various life
      periods and risk of exfoliation glaucoma or exfoliation glaucoma suspect. DESIGN:
      Retrospective cohort study in the United States. METHODS: Participants (49 033
      women in the Nurses Health Study and 20 066 men in the Health Professionals
      Follow-up Study) were 60+ years old, were free of glaucoma and cataract, reported
      eye examinations, and completed questions about time spent outdoors in direct
      sunlight at midday at 3 life periods: high school to age 24 years, age 25-35
      years, and age 36-59 years (asked in 2006 in women and 2008 in men). Participants
      were followed biennially with mailed questionnaires from 1980 women/1986 men to
      2010. Incident cases (223 women and 38 men) were confirmed with medical records.
      Cohort-specific multivariable-adjusted rate ratios from Cox proportional hazards
      models were estimated and pooled with meta-analysis. RESULTS: Although no
      association was observed with greater time spent outdoors in the ages of 25-35 or
      ages 36-59 years, the pooled multivariable-adjusted rate ratios for >=11 hours
      per week spent outdoors in high school to age 24 years compared with <=5 hours
      per week was 2.00 (95% confidence interval = 1.30, 3.08; P for linear trend =
      .001). In women, this association was stronger in those who resided in the
      southern geographic tier in young adulthood (P for interaction = .07).
      CONCLUSIONS: Greater time spent outdoors in young adulthood was associated with
      risk of exfoliation glaucoma or exfoliation glaucoma suspect, supporting an
      etiologic role of early exposures to climatic factors.

PMID- 24857691
TI  - The redox-Mannich reaction.
AB  - A complement to the classic three-component Mannich reaction, the redox-Mannich
      reaction, utilizes the same starting materials but incorporates an isomerization
      step that enables the facile preparation of ring-substituted beta-amino ketones.
      Reactions occur under relatively mild conditions and are facilitated by benzoic
      acid. 

PMID- 24857693
TI  - How best to interpret mixed human papillomavirus genotypes in high-grade cervical
      intraepithelial neoplasia lesions.
AB  - OBJECTIVES: This study aimed to determine human papillomavirus (HPV) genotypes
      present in biopsy sections from young women of vaccine eligible age living in
      Victoria, Australia, with confirmed cervical intraepithelial neoplasia grade 3
      (CIN3) or adenocarcinoma in situ (AIS) using laser capture microdissection (LCM).
      METHODS: Histologically confirmed CIN3 or AIS positive biopsies from vaccine
      eligible women (born after 30th June 1981, n=169), between May 2011 and March
      2013, were identified. CIN3 or AIS lesions were isolated from biopsy material
      using LCM, and the HPV genotypes present in whole tissue sections (WTS) as well
      as LCM-isolated lesion tissue were determined by a sensitive reverse
      hybridisation assay; RHA kit HPV SPF10-LiPA25, version 1 (Labo Bio-medical
      Products, Rijswijk, The Netherlands). RESULTS: One hundred and sixty-eight cases
      were shown to be HPV positive (99%), of which 20 (12%) had more than one HPV
      genotype detected using WTS-PCR. Evaluation by LCM of individual biopsies with
      mixed infections showed 18 cases (90%) had only one HPV genotype associated with
      each CIN3 lesion. HPV 16 was the most common HPV type, found in 95/168 cases
      (57%). CONCLUSION: LCM-PCR allowed us to confirm the presence of a single HPV
      genotype associated with each biologically separate CIN3 lesion, supporting the
      theory that only one virus type causes each independent CIN lesion. LCM will
      provide an important tool in assessing vaccine effectiveness in HPV vaccine
      programs.

PMID- 24857695
TI  - Radiation treatment for newly diagnosed esophageal cancer with prior radiation to
      the thoracic cavity.
AB  - The purpose of this report is to communicate the use of single-positron emission
      computed tomography scan in planning radiation treatments for patients with a
      history of radiation to the thoracic cavity. A patient presented with obstructive
      esophageal cancer, having previously received chemotherapy and radiation therapy
      to the mediastinum for non-Hodgkin lymphoma 11 years earlier. Owing to a number
      of comorbidities, the patient was not a surgical candidate and was referred to
      the University of Washington Medical Center for radiation therapy. Prior dose to
      the spinal cord and lung were taken into account before designing the radiation
      treatment plan. 

PMID- 24857696
TI  - Volumetric-modulated arc radiotherapy for pancreatic malignancies: dosimetric
      comparison with sliding-window intensity-modulated radiotherapy and 3-dimensional
      conformal radiotherapy.
AB  - Volumetric-modulated arc radiotherapy (VMAT) is an iteration of intensity
      modulated radiotherapy (IMRT), both of which deliver highly conformal dose
      distributions. Studies have shown the superiority of VMAT and IMRT in comparison
      with 3-dimensional conformal radiotherapy (3D-CRT) in planning target volume
      (PTV) coverage and organs-at-risk (OARs) sparing. This is the first study
      examining the benefits of VMAT in pancreatic cancer for doses more than 55.8 Gy.
      A planning study comparing 3D-CRT, IMRT, and VMAT was performed in 20 patients
      with pancreatic cancer. Treatments were planned for a 25-fraction delivery of 45
      Gy to a large field followed by a reduced-volume 8-fraction external beam boost
      to 59.4 Gy in total. OARs and PTV doses, conformality index (CI) deviations from
      1.0, monitor units (MUs) delivered, and isodose volumes were compared. IMRT and
      VMAT CI deviations from 1.0 for the large-field and the boost plans were
      equivalent (large field: 0.032 and 0.046, respectively; boost: 0.042 and 0.037,
      respectively; p > 0.05 for all comparisons). Both IMRT and VMAT CI deviations
      from 1.0 were statistically superior to 3D-CRT (large field: 0.217, boost: 0.177;
      p < 0.05 for all comparisons). VMAT showed reduction of the mean dose to the
      boost PTV (VMAT: 61.4 Gy, IMRT: 62.4 Gy, and 3D-CRT: 62.3 Gy; p < 0.05). The mean
      number of MUs per fraction was significantly lower for VMAT for both the large
      field and the boost plans. VMAT delivery time was less than 3 minutes compared
      with 8 minutes for IMRT. Although no statistically significant dose reduction to
      the OARs was identified when comparing VMAT with IMRT, VMAT showed a reduction in
      the volumes of the 100% isodose line for the large-field plans. Dose escalation
      to 59.4 Gy in pancreatic cancer is dosimetrically feasible with shorter treatment
      times, fewer MUs delivered, and comparable CIs for VMAT when compared with IMRT.

PMID- 24857694
TI  - An enhancer polymorphism at the cardiomyocyte intercalated disc protein NOS1AP
      locus is a major regulator of the QT interval.
AB  - QT interval variation is assumed to arise from variation in repolarization as
      evidenced from rare Na- and K-channel mutations in Mendelian QT prolongation
      syndromes. However, in the general population, common noncoding variants at a
      chromosome 1q locus are the most common genetic regulators of QT interval
      variation. In this study, we use multiple human genetic, molecular genetic, and
      cellular assays to identify a functional variant underlying trait association: a
      noncoding polymorphism (rs7539120) that maps within an enhancer of NOS1AP and
      affects cardiac function by increasing NOS1AP transcript expression. We further
      localized NOS1AP to cardiomyocyte intercalated discs (IDs) and demonstrate that
      overexpression of NOS1AP in cardiomyocytes leads to altered cellular
      electrophysiology. We advance the hypothesis that NOS1AP affects cardiac
      electrical conductance and coupling and thereby regulates the QT interval through
      propagation defects. As further evidence of an important role for propagation
      variation affecting QT interval in humans, we show that common polymorphisms
      mapping near a specific set of 170 genes encoding ID proteins are significantly
      enriched for association with the QT interval, as compared to genome-wide
      markers. These results suggest that focused studies of proteins within the
      cardiomyocyte ID are likely to provide insights into QT prolongation and its
      associated disorders. 

PMID- 24857697
TI  - Left-sided breast cancer irradiation using rotational and fixed-field
      radiotherapy.
AB  - The 3-dimensional conformal radiotherapy (3DCRT) technique is the standard for
      breast cancer radiotherapy. During treatment planning, not only the coverage of
      the planning target volume (PTV) but also the minimization of the dose to
      critical structures, such as the lung, heart, and contralateral breast tissue,
      need to be considered. Because of the complexity and variations of patient
      anatomy, more advanced radiotherapy techniques are sometimes desired to better
      meet the planning goals. In this study, we evaluated external-beam radiation
      treatment techniques for left breast cancer using various delivery platforms:
      fixed-field including TomoDirect (TD), static intensity-modulated radiotherapy
      (sIMRT), and rotational radiotherapy including Elekta volumetric-modulated arc
      therapy (VMAT) and tomotherapy helical (TH). A total of 10 patients with left
      sided breast cancer who did or did not have positive lymph nodes and were
      previously treated with 3DCRT/sIMRT to the entire breast were selected, their
      treatment was planned with Monaco VMAT, TD, and TH. Dosimetric parameters
      including PTV coverage, organ-at-risk (OAR) sparing, dose-volume histograms, and
      target minimum/maximum/mean doses were evaluated. It is found that for plans
      providing comparable PTV coverage, the Elekta VMAT plans were generally more
      inhomogeneous than the TH and TD plans. For the cases with regional node
      involvement, the average mean doses administered to the heart were 9.2 (+/- 5.2)
      and 8.8 (+/- 3.0)Gy in the VMAT and TH plans compared with 11.9 (+/- 6.4) and
      11.8 (+/- 9.2)Gy for the 3DCRT and TD plans, respectively, with slightly higher
      doses given to the contralateral lung or breast or both. On average, the total
      monitor units for VMAT plans are 11.6% of those TH plans. Our studies have shown
      that VMAT and TH plans offer certain dosimetric advantages over fixed-field IMRT
      plans for advanced breast cancer requiring regional nodal treatment. However, for
      early-stage breast cancer fixed-field radiotherapy is potentially more beneficial
      in terms of OAR sparing. 

PMID- 24857698
TI  - Thyroid hormones and fear learning but not anxiety are affected in adult apoE
      transgenic mice exposed postnatally to decabromodiphenyl ether (BDE-209).
AB  - Polybrominated diphenyl ethers (PBDEs) are a family of industrial chemicals used
      as flame retardants. The fully brominated deca-BDE (BDE-209) is the most used and
      its potential risk for humans is controversial. The ability of PBDEs to target
      nervous and endocrine systems suggests multiple enduring effects after perinatal
      exposure. Cognitive and motor behavior alterations have been reported after
      developmental exposure to PBDEs, including BDE-209, whereas very little work has
      been carried out on anxiety and emotional learning. We have previously reported
      long-term effects of postnatal BDE-209 exposure on spatial memory dependent upon
      apolipoprotein E (apoE) polymorphism and age. ApoE is involved in lipid transport
      and its different polymorphisms (epsilon2, epsilon3, epsilon4) confer different
      vulnerabilities to neurodegeneration, cognitive impairment and anxiety. In the
      present study we assessed the long term effects of early exposure to BDE-209 on
      anxiety, fear learning and thyroid hormone levels in mice carrying different apoE
      polymorphisms (epsilon2, epsilon3, epsilon4). BDE-209 (0, 10 and 30 mg/kg) was
      orally administered on postnatal day 10 (PND 10). At 4 and 12 months of age mice
      were tested in an open field (OF) and an elevated zero maze (EZM). Fear
      conditioning and thyroid hormone levels were evaluated in mice at 5-6 months of
      age. Postnatal exposure to BDE-209 impaired cued fear learning in apoE2 and apoE3
      mice. Levels of thyroid hormones were increased in apoE3 female mice exposed to
      BDE-209. Our findings indicate long lasting effects of BDE-209 on emotional
      learning and thyroid hormone levels after a single postnatal exposure.

PMID- 24857701
TI  - Infection control and MERS-CoV in health-care workers.

PMID- 24857700
TI  - London 2012 Olympic and Paralympic Games: public health surveillance and
      epidemiology.
AB  - Mass gatherings are regarded as potential risks for transmission of infectious
      diseases, and might compromise the health system of countries in which they are
      hosted. The evidence for increased transmission of infectious diseases at
      international sporting mass gatherings that attract many visitors from all over
      the world is not clear, and the evidence base for public health surveillance,
      epidemiology, and response at events such as the Olympics is small. However,
      infectious diseases are a recognised risk, and public health planning is, and
      should remain, a crucial part of the overall planning of sporting events. In this
      Series paper, we set out the planning and the surveillance systems that were used
      to monitor public health risks during the London 2012 Olympic and Paralympic
      Games in the summer of 2012, and draw attention to the public health issues
      infectious diseases and chemical, radiation, and environmental hazards-that
      arose. Although the absolute risk of health-protection problems, including
      infectious diseases, at sporting mass gatherings is small, the need for
      reassurance of the absence of problems is higher than has previously been
      considered; this could challenge conventional public health surveillance systems.
      Recognition of the limitations of health-surveillance systems needs to be part of
      the planning for future sporting events. 

PMID- 24857702
TI  - Ziad Memish: father of mass gatherings medicine.

PMID- 24857703
TI  - Hajj: infectious disease surveillance and control.
AB  - Religious festivals attract a large number of pilgrims from worldwide and are a
      potential risk for the transmission of infectious diseases between pilgrims, and
      to the indigenous population. The gathering of a large number of pilgrims could
      compromise the health system of the host country. The threat to global health
      security posed by infectious diseases with epidemic potential shows the
      importance of advanced planning of public health surveillance and response at
      these religious events. Saudi Arabia has extensive experience of providing health
      care at mass gatherings acquired through decades of managing millions of pilgrims
      at the Hajj. In this report, we describe the extensive public health planning,
      surveillance systems used to monitor public health risks, and health services
      provided and accessed during Hajj 2012 and Hajj 2013 that together attracted more
      than 5 million pilgrims from 184 countries. We also describe the recent
      establishment of the Global Center for Mass Gathering Medicine, a Saudi
      Government partnership with the WHO Collaborating Centre for Mass Gatherings
      Medicine, Gulf Co-operation Council states, UK universities, and public health
      institutions globally. 

PMID- 24857704
TI  - Mass gatherings medicine: international cooperation and progress.

PMID- 24857705
TI  - Euro 2012 European Football Championship Finals: planning for a health legacy.
AB  - The revised international health regulations offer a framework that can be used
      by host countries to organise public health activities for mass gatherings. From
      June 8, to July 1, 2012, Poland and Ukraine jointly hosted the Union of European
      Football Associations European Football Championship Finals (Euro 2012). More
      than 8 million people from around the world congregated to watch the games. Host
      countries and international public health agencies planned extensively to assess
      and build capacity in the host countries and to develop effective strategies for
      dissemination of public health messages. The effectiveness of public health
      services was maximised through rapid sharing of information between parties,
      early use of networks of experienced individuals, and the momentum of existing
      national health programmes. Organisers of future mass gatherings for sporting
      events should share best practice and their experiences through the WHO
      International Observer Program. Research about behaviour of large crowds is
      needed for crowd management and the evidence base translated into practice. A
      framework to measure and evaluate the legacy of Euro 2012 is needed based on the
      experiences and the medium-term and long-term benefits of the tournament. 

PMID- 24857706
TI  - Formaldehyde content of atmospheric aerosol.
AB  - Formaldehyde (HCHO) is a highly soluble polar molecule with a large sticking
      coefficient and thus likely exists in both gaseous and particulate forms. Few
      studies, however, address particulate HCHO (HCHO(p)). Some report that HCHO(p)
      concentrations (obtained only with long duration sampling) are very low. The lack
      of data partly reflects the difficulty of specifically measuring HCHO(p). Long
      duration filter sampling may not produce meaningful results for a variety of
      reasons. In this work, gaseous HCHO (HCHO(g)) and (HCHO(p)) were, respectively,
      collected with a parallel plate wet denuder (PPWD) followed by a mist
      chamber/hydrophilic filter particle collector (PC). The PPWD quantitatively
      removed HCHO(g) and the PC then collected the transmitted aerosol. The collected
      HCHO from either device was alternately analyzed by Hantzsch reaction-based
      continuous flow fluorometry. Each gas and particle phase measurement took 5 min
      each, with a 10 min cycle. The limits of detection were 0.048 and 0.0033 MUg m(
      3), respectively, for HCHO(g) and HCHO(p). The instrument was deployed in three
      separate campaigns in a forest station in western Japan in March, May, and July
      of 2013. Based on 1296 data pairs, HCHO(p), was on the average, 5% of the total
      HCHO. Strong diurnal patterns were observed, with the HCHO(p) fraction peaking in
      the morning. The relative humidity dependence of the partition strongly suggests
      that it is driven by the liquid water content of the aerosol phase. However,
      HCHO(p) was 100* greater than that expected from Henry's law. We propose that the
      low water activity in the highly saline droplets lead to HCHO oligomerization. 

PMID- 24857707
TI  - Wartime upper extremity injuries: experience from the Kabul International Airport
      combat support hospital.
AB  - Few epidemiologic studies have been published about the surgical management of
      wartime upper extremity injuries (UEIs). The purpose of the present report was to
      analyze upper extremity combat-related injuries (CRIs) and non-combat related
      injuries (NCRIs) treated in the Kabul International Airport Combat Support
      Hospital. A retrospective study was conducted using the French surgical database
      OpEX (French military health service) from June 2009 to January 2013. During this
      period, 491 patients with a mean age of 28.7 +/- 13 years were operated on
      because of an UEI. Among them, 244 (49.7%) sustained CRIs and 247 (50.3%)
      sustained NCRIs. A total number of 558 UEIs were analyzed. Multiple UEIs and
      associated injuries were significantly more common in the CRIs group. Debridement
      was the most common procedure in both groups. External fixator application,
      delayed primary closure and flap coverage were predominant in the CRIs group, as
      well as internal fracture fixation and tendon repair in the NCRIs group. The
      overall number of surgical episodes was significantly higher in the CRIs group.
      Due to the high frequency of UEIs in the theatres of operations, deployed
      orthopedic surgeons should be trained in basic hand surgery. Although the
      principles of CRIs treatment are well established, management of hand NCRIs
      remains controversial in this setting.

PMID- 24857708
TI  - Effective virtual screening strategy toward covalent ligands: identification of
      novel NEDD8-activating enzyme inhibitors.
AB  - The NEDD8-activating enzyme (NAE) is an emerging target for cancer therapy, which
      regulates the degradation and turnover of a variety of cancer-related proteins by
      activating the cullin-RING E3 ubiquitin ligases. Among a limited number of known
      NAE inhibitors, the covalent inhibitors have demonstrated the most potent
      efficacy through their covalently linked adducts with NEDD8. Inspired by this
      unique mechanism, in this study, a novel combined strategy of virtual screening
      (VS) was adopted with the aim to identify diverse covalent inhibitors of NAE. To
      be specific, a docking-enabled pharmacophore model was first built from the
      possible active conformations of chosen covalent inhibitors. Meanwhile, a dynamic
      structure-based phamacophore was also established based on the snapshots derived
      from molecular dynamic simulation. Subsequent screening of a focused ZINC
      database using these pharmacophore models combined with covalent docking
      discovered three novel active compounds. Among them, compound LZ3 exhibited the
      most potent NAE inhibitory activity with an IC50 value of 1.06 +/- 0.18 MUM.
      Furthermore, a cell-based washout experiment proved the proposed covalent binding
      mechanism for compound LZ3, which confirmed the successful application of our
      combined VS strategy, indicating it may provide a viable solution to
      systematically discover novel covalent ligands. 

PMID- 24857709
TI  - Neuroplasticity of prehensile neural networks after quadriplegia.
AB  - Targeting cortical neuroplasticity through rehabilitation-based practice is
      believed to enhance functional recovery after spinal cord injury (SCI). While
      prehensile performance is severely disturbed after C6-C7 SCI, subjects with
      tetraplegia can learn a compensatory passive prehension using the tenodesis
      effect. During tenodesis, an active wrist extension triggers a passive flexion of
      the fingers allowing grasping. We investigated whether motor imagery training
      could promote activity-dependent neuroplasticity and improve prehensile tenodesis
      performance. SCI participants (n=6) and healthy participants (HP, n=6) took part
      in a repeated measurement design. After an extended baseline period of 3 weeks
      including repeated magnetoencephalography (MEG) measurements, MI training was
      embedded within the classical course of physiotherapy for 5 additional weeks
      (three sessions per week). An immediate MEG post-test and a follow-up at 2 months
      were performed. Before MI training, compensatory activations and recruitment of
      deafferented cortical regions characterized the cortical activity during actual
      and imagined prehension in SCI participants. After MI training, MEG data yielded
      reduced compensatory activations. Cortical recruitment became similar to that in
      HP. Behavioral analysis evidenced decreased movement variability suggesting motor
      learning of tenodesis. Data suggest that MI training participated to reverse
      compensatory neuroplasticity in SCI participants, and promoted the integration of
      new upper limb prehensile coordination in the neural networks functionally
      dedicated to the control of healthy prehension before injury.

PMID- 24857710
TI  - A closer look at mechanisms underlying perceptual differences in Parkinson's
      freezers and non-freezers.
AB  - Parkinson's disease patients who suffer from freezing of gait (PD-FOG) may have
      sensory and/or perceptual deficits, although they are difficult to disentangle.
      This study evaluated whether visuospatial perception or self-motion perception
      were more impaired in PD-FOG, and whether distance estimation errors might be
      related to misperception of physical walking (compared to imagined). Finally,
      cognitive status was evaluated in order to evaluate whether cognitive status
      predicts any of the perception deficits identified. Nine PD-FOG and 15 PD-nonFOG
      were tested. In experiment 1, participants were shown a target, then the target
      was removed, before participants demonstrated the original position of the target
      in two different feedback conditions (pointing with a laser, or walking to its
      original position). In experiment 2, participants walked to a target (3, 4.5, 6m)
      and then imagined walking to that same target. The time to complete both of these
      tasks was measured and compared. Experiment 1 found a significantly greater
      judgment error in PD-FOG across both conditions (p=0.013) (compared to PD
      nonFOG). Constant error revealed that both groups significantly underestimated
      during the self-motion condition only (p=0.01). Interestingly, results from
      experiment 2 demonstrated a significant discrepancy between the time it took to
      imagine walking compared to their actual movement times, specifically in PD-FOG
      (p=0.03). This mismatch as well as cognitive status significantly predicted
      judgment errors during the self-motion condition from experiment 1. Therefore,
      this study found evidence that PD-FOG have significantly greater sensory
      perception deficits compared to PD-nonFOG. These findings have important clinical
      implications for further understanding FOG and developing new rehabilitative
      strategies for FOG symptoms. 

PMID- 24857711
TI  - Prenatal stress leads to changes in IGF-1 binding proteins network in the
      hippocampus and frontal cortex of adult male rat.
AB  - Depression is a mental disorder of still unknown origin. Currently, much
      attention is paid to the potential influence of disturbances in the functioning
      of neurotrophic factors on the onset of this disease. Insulin-like growth factor
      1 (IGF-1) is one of the most important growth agents affecting processes that are
      crucial for brain development. To date, there are no data showing the impact of
      prenatal stress on the family of six IGF binding proteins (IGFBP 1-6) that
      regulate IGF-1 bioactivity. The goal of this study was to investigate whether the
      decreased expression of IGF-1 in the frontal cortex (FCx) and hippocampus (Hp) of
      adult male rats following a prenatal stress procedure is related to changes in
      the IGFBP family. Our results show that rats exposed prenatally to stressful
      stimuli displayed depression-like behavior based on sucrose preference and
      elevated plus maze tests. In both cases, in the adult rat brain structures that
      were examined after the prenatal stress procedure, the IGF-1 protein level was
      reduced. Moreover, we observed changes of varying degrees in the levels of IGFBPs
      in stressed animals. A decrease in IGFBP-2 and IGFBP-3 accompanied by an increase
      in the IGFBP-4 concentration in the Hp and the FCx was detected. There were no
      differences in IGFBP-1 and IGFBP-6 brain levels between the stressed and control
      animals, whereas IGFBP-5 concentration was decreased in the Hp of prenatally
      stressed animals. This study demonstrated that stress during pregnancy may lead
      not only to behavioral disturbances but also to a decrease in IGF-1 level and the
      dysregulation of the IGF-1 binding protein network in adult rat offspring. 

PMID- 24857712
TI  - Contributors to contrast between glioma and brain tissue in chemical exchange
      saturation transfer sensitive imaging at 3 Tesla.
AB  - Off-resonance saturation transfer images have shown intriguing differences in
      intensity in glioma compared to normal brain tissues. Interpretation of these
      differences is complicated, however, by the presence of multiple sources of
      exchanging magnetization including amide, amine, and hydroxyl protons, asymmetric
      magnetization transfer contrast (MTC) from macromolecules, and various protons
      with resonances in the aliphatic spectral region. We report a study targeted at
      separating these components and identifying their relative contributions to
      contrast in glioma. Off-resonance z-spectra at several saturation powers and
      durations were obtained from 6 healthy controls and 8 patients with high grade
      glioma. Results indicate that broad macromolecular MTC in normal brain tissue is
      responsible for the majority of contrast with glioma. Amide exchange could be
      detected with lower saturation power than has previously been reported in glioma,
      but it was a weak signal source with no detectable contrast from normal brain
      tissue. At higher saturation powers, amine proton exchange was a major
      contributor to the observed signal but showed no significant difference from
      normal brain. Robust acquisition strategies that effectively isolate the
      contributions of broad macromolecular MTC asymmetry from amine exchange were
      demonstrated that may provide improved contrast between glioma and normal tissue.

PMID- 24857713
TI  - Abnormal metabolic connectivity in the pilocarpine-induced epilepsy rat model: a
      multiscale network analysis based on persistent homology.
AB  - Temporal lobe epilepsy is associated with dysfunctional brain networks. Here we
      investigated metabolic connectivity in the pilocarpine-induced epilepsy rat model
      and applied a new multiscale framework to the analysis of metabolic networks of
      small-animal brains. [(18)F]fluorodeoxyglucose PET was acquired in pilocarpine
      induced chronic epilepsy rats and controls to yield interregional metabolic
      correlation by inter-subject manner. When interregional correlation of epilepsy
      rats and controls was compared directly, the epilepsy rats showed reduced
      connectivity involving the left amygdala and left entorhinal cortex. When
      regional graph properties were calculated to characterize abnormal nodes in the
      epileptic brain network, the epilepsy rats showed reduced nodal and local
      efficiencies in the left amygdala. Then, a new multiscale framework, persistent
      brain network homology, was used to examine metabolic connectivity with a
      threshold-free approach and the difference between two networks was analyzed
      using single linkage distances (SLDs) of all pairwise nodes. We found a tendency
      for longer SLDs between the left insula/left amygdala and bilateral
      cortical/subcortical structures in the epilepsy rats. Persistent brain network
      homology analysis as well as interregional correlation study implied the abnormal
      left limbic-paralimbic-neocortical network in the pilocarpine-induced epilepsy
      rat models. In conclusion, we found a globally disrupted network in the epileptic
      brain in rats, particularly in the limbic and paralimbic structures by direct
      comparison, graph properties and multiscale network analysis. These results
      demonstrate that the multiscale and threshold-free network analysis can be used
      to find the network abnormality in small-animal brains as a preclinical research.

PMID- 24857714
TI  - Sex differences in volume and structural covariance of the anterior and posterior
      hippocampus.
AB  - Sex differences in episodic and spatial memory are frequently observed,
      suggesting that there may be sex-related structural differences in the
      hippocampus (HC). Earlier findings are inconsistent, possibly due to a known
      variability along the hippocampal longitudinal axis. Here, we assessed potential
      sex differences in hippocampal volume and structural covariance with the rest of
      the brain in young men and women (N=76), considering the anterior (aHC) and
      posterior (pHC) hippocampus separately. Women exhibited a larger pHC than men
      adjusted for brain size. Using partial least squares, we identified two
      significant patterns of structural covariance of the aHC and pHC. The first
      included brain areas that covaried positively and negatively in volume with both
      the aHC and pHC in men, but showed greater covariance with the aHC than pHC in
      women. The second pattern revealed distinct structural covariance of the aHC and
      pHC that showed a clear difference between men and women: in men the pHC showed
      reliable structural covariance with the medial and lateral parietal lobes and the
      prefrontal cortex, whereas in women the aHC showed reliable structural covariance
      with the anterior temporal lobe bilaterally. This pattern converges with resting
      state functional connectivity of the aHC and pHC and suggests that these
      hippocampal sections interact with different brain regions, consistent with a
      division of labor with regards to episodic and spatial memory. Our findings lend
      support to a division of the HC into an anterior and posterior part and identify
      sex as a potential moderating factor when investigating hippocampal structure and
      connectivity. 

PMID- 24857715
TI  - The role of prefrontal and parietal cortices in esthetic appreciation of
      representational and abstract art: a TMS study.
AB  - To explain the biological foundations of art appreciation is to explain one of
      our species' distinctive traits. Previous neuroimaging and electrophysiological
      studies have pointed to the prefrontal and the parietal cortex as two critical
      regions mediating esthetic appreciation of visual art. In this study, we applied
      transcranial magnetic stimulation (TMS) over the left prefrontal cortex and the
      right posterior parietal cortex while participants were evaluating whether they
      liked, and by how much, a particular painting. By depolarizing cell membranes in
      the targeted regions, TMS transiently interferes with the activity of specific
      cortical areas, which allows clarifying their role in a given task. Our results
      show that both regions play a fundamental role in mediating esthetic
      appreciation. Critically though, the effects of TMS varied depending on the type
      of art considered (i.e. representational vs. abstract) and on participants' a
      priori inclination toward one or the other. 

PMID- 24857716
TI  - Reply: To PMID 24113255.

PMID- 24857717
TI  - Neonatal Escherichia coli K1 meningitis causes learning and memory impairments in
      adulthood.
AB  - Neonatal Escherichia coli meningitis continues to be an important cause of
      mortality and morbidity in newborns worldwide. The aim of this study was to
      investigate the cytokines/chemokines, brain-derived neurotrophic factor (BDNF)
      levels, blood-brain barrier integrity in neonatal rats following E. coli K1
      experimental meningitis infection and subsequent behavioural parameters in
      adulthood. In the hippocampus, interleukin increased at 96 h, IL-6 at 12, 48 and
      96 h, IL-10 at 96 h, cytokine-induced neutrophil chemoattractant-1 at 6, 12, 24,
      48 and 96 h, and BDNF at 48 and 96 h. In the cerebrospinal fluid, tumour necrosis
      factor alpha levels increased at 6, 12, 24, 48 and 96 h. The BBB breakdown
      occurred at 12 h in the hippocampus, and at 6h in the cortex. We evaluated
      behavioural parameters in adulthood: habituation to the open-field, step-down
      inhibitory avoidance, object recognition, continuous multiple-trials step-down
      inhibitory avoidance and forced swimming tasks. In adulthood, the animals showed
      habituation and aversive memory impairment. The animals needed a significant
      increase in the number of training periods to learn and not had depressive-like
      symptoms.

PMID- 24857719
TI  - Increased number of chews during a fixed-amount meal suppresses postprandial
      appetite and modulates glycemic response in older males.
AB  - Aging is associated with a reduction in appetite. Older adults require a higher
      number of chews to form a bolus before swallowing. However, whether this
      ingestive behavior contributes to the reduced appetite in this population is
      unknown. Fifteen males aged 65 years or older participated in this randomized
      cross-over trial and attended two test sessions. After an overnight fast, they
      consumed a fixed-amount meal (2050 kJ) by chewing each portion of food 15 or 40
      times before swallowing. Subjective appetite was measured using visual analogue
      scales at regular intervals for 3 h after completion of the meal. Blood samples
      were collected at the same time for measurement of glucose, insulin, and glucose
      dependent insulinotropic peptide (GIP). Participants were provided an ad libitum
      meal 3 h later. Compared with 15 chews, chewing food 40 times before swallowing
      resulted in significantly lower postprandial hunger (P=0.003), preoccupation with
      food (P<0.001), and desire to eat (P<0.001). Plasma concentrations of glucose,
      insulin, and GIP were significantly higher at meal completion when 40 chews were
      made (all P<0.01), and became significantly lower during the late postprandial
      period (all P<0.05). Food intake at the subsequent ad libitum meal did not differ
      significantly between test sessions. Our findings suggested that increased number
      of chews reduced postprandial hunger and desire to eat, and modulated glucose
      metabolism in older males. The number of chews made during a fixed-amount meal
      may influence short-term appetite; how this ingestive behavior contributes to
      energy balance in the long term warrants further investigation.

PMID- 24857720
TI  - Effects of neonatal oxytocin manipulation on development of social behaviors in
      mice.
AB  - The oxytocin (OT) neural system is thought to be involved in the underlying
      mechanisms that guide the development of social behaviors. In the present study,
      we examined the effects of neonatal oxytocin manipulation in mice. Within 24
      hours after birth, pups in the treatment group randomly received an
      intraperitoneal injection of OT or OT antagonist (OTA), and those in the control
      group received a saline injection or handling only. Some of these mice underwent
      a test that counted the number of isolation-induced ultrasound vocalizations they
      made on postnatal day 6, and they were further tested for sociability at 8-9
      weeks of age and for neuroendocrine stress response to novel environments at 19
      20 weeks of age. Another group of mice was tested for alloparental responsiveness
      at 13-15 weeks of age. The OT injection affected sociability and alloparental
      responsiveness. In an approach/avoidance test, most of the mice made a social
      approach to an unfamiliar conspecific of the same sex, but females that had
      received a neonatal injection of 3 MUg of OTA did not show this response. The
      neonatal OTA treatment appeared to inhibit females' sociability in a dose
      dependent fashion. In a retrieving test, females that had received a neonatal
      injection of 3 MUg of OT retrieved significantly more pups than did those that
      had received 3 MUg of OTA, although neither of the treatments caused the females
      to behave significantly differently from control group females. Meanwhile, a
      neonatal injection of 3 MUg of OTA increased the latency to retrieve pups in
      males. These results suggested that neonatal OT action may positively regulate
      alloparental responsiveness in adulthood. Considering that the organizational
      effects of OT have also been shown in voles and rats, the mechanism by which
      neonatal OT modifies the development of social behaviors appears to be common to
      all rodents.

PMID- 24857721
TI  - Exposure to dim light at night during early development increases adult anxiety
      like responses.
AB  - Early experiences produce effects that may persist throughout life. Therefore, to
      understand adult phenotype, it is important to investigate the role of early
      environmental stimuli in adult behavior and health. Artificial light at night
      (LAN) is an increasingly common phenomenon throughout the world. However,
      animals, including humans, evolved under dark night conditions. Many studies have
      revealed affective, immune, and metabolic alterations provoked by aberrant light
      exposure and subsequent circadian disruption. Pups are receptive to entraining
      cues from the mother and then light early during development, raising the
      possibility that the early life light environment may influence subsequent
      behavior. Thus, to investigate potential influences of early life exposure to LAN
      on adult phenotype, we exposed mice to dim (~5 lux; full spectrum white light) or
      dark (~0 lux) nights pre- and/or postnatally. After weaning at 3 weeks of age,
      all mice were maintained in dark nights until adulthood (9 weeks of age) when
      behavior was assessed. Mice exposed to dim light in early life increased anxiety
      like behavior and fearful responses on the elevated plus maze and passive
      avoidance tests. These mice also displayed reduced growth rates, which ultimately
      normalized during adolescence. mRNA expression of brain derived neurotrophic
      factor (BDNF), a neurotrophin previously linked to early life environment and
      adult phenotype, was not altered in the prefrontal cortex or hippocampus by early
      life LAN exposure. Serum corticosterone concentrations were similar between
      groups at weaning, suggesting that early life LAN does not elicit a long-term
      physiologic stress response. Dim light exposure did not influence behavior on the
      open field, novel object, sucrose anhedonia, or forced swim tests. Our data
      highlight the potential deleterious consequences of low levels of light during
      early life to development and subsequent behavior. Whether these changes are due
      to altered maternal behavior or persistent circadian abnormalities incurred by
      LAN remains to be determined.

PMID- 24857722
TI  - Effects and after-effects of chewing gum on vigilance, heart rate, EEG and mood.
AB  - Research has shown that chewing gum improves attention, although the mechanism
      for this effect remains unclear. This study investigated the effects and after
      effects of chewing gum on vigilance, mood, heart rate and EEG. Participants
      completed a vigilance task four times; at baseline, with or without chewing gum,
      and twice post-chewing. EEG alpha and beta power at left frontal and temporal
      lobes, subjective mood and heart rate were assessed. Chewing gum shortened
      reaction time and increased the rate of hits, although hits fell during the
      second post-chewing task. Chewing gum heightened heart rate, but only during
      chewing. Gum also increased beta power at F7 and T3 immediately post-chewing, but
      not following the post-chewing tasks. The findings show that chewing gum affects
      several different indicators of alertness. 

PMID- 24857723
TI  - Fifty years of nuclear pores and nucleocytoplasmic transport studies: multiple
      tools revealing complex rules.
AB  - Nuclear pore complexes (NPCs) are multiprotein assemblies embedded within the
      nuclear envelope and involved in the control of the bidirectional transport of
      proteins and ribonucleoparticles between the nucleus and the cytoplasm. Since
      their discovery more than 50 years ago, NPCs and nucleocytoplasmic transport have
      been the focus of intense research. Here, we review how the use of a multiplicity
      of structural, biochemical, genetic, and cell biology approaches have permitted
      the deciphering of the main features of this macromolecular complex, its mode of
      assembly as well as the rules governing nucleocytoplasmic exchanges. We first
      present the current knowledge of the ultrastructure of NPCs, which reveals that
      they are modular and repetitive assemblies of subunits referred to as
      nucleoporins, associated into stable subcomplexes and composed of a limited set
      of protein domains, including phenylalanine-glycine (FG) repeats and membrane
      interacting domains. The outcome of investigations on nucleocytoplasmic
      trafficking will then be detailed, showing how it involves a limited number of
      molecular factors and common mechanisms, namely (i) indirect association of
      cargos with nuclear pores through receptors in the donor compartment, (ii)
      progression within the channel through dynamic hydrophobic interactions with FG
      Nups, and (iii) NTPase-driven remodeling of transport complexes in the target
      compartment. Finally, we also discuss the outcome of more recent studies, which
      indicate that NPCs and the transport machinery are dynamic and versatile devices,
      whose biogenesis is tightly coordinated with the cell cycle, and which carry
      nonconventional duties, in particular, in mitosis, gene expression, and genetic
      stability. 

PMID- 24857724
TI  - Imaging metazoan nuclear pore complexes by field emission scanning electron
      microscopy.
AB  - High resolution three-dimensional surface images of nuclear pore complexes (NPCs)
      can be obtained by field emission scanning electron microscopy. We present a
      short retrospective view starting from the early roots of microscopy, through the
      discovery of the cell nucleus and the development of some modern techniques for
      sample preparation and imaging. Detailed protocols are presented for assembling
      anchored nuclei in a Xenopus cell-free reconstitution system and for the exposure
      of the nuclear surface in mammalian cell nuclei. Immunogold labeling of metazoan
      NPCs and a promising new technique for delicate coating with iridium are also
      discussed. 

PMID- 24857725
TI  - Imaging yeast NPCs: from classical electron microscopy to Immuno-SEM.
AB  - Electron microscopy (EM) has been used extensively for the study of nuclear
      transport as well as the structure of the nuclear pore complex (NPC) and nuclear
      envelope. However, there are specific challenges faced when carrying out EM in
      one of the main model organisms used: the yeast, Saccharomyces cerevisiae. These
      are due to the presence of a cell wall, vacuoles, and a densely packed cytoplasm
      which, for transmission EM (TEM), make fixation, embedding, and imaging
      difficult. These also present problems for scanning EM (SEM) because cell wall
      removal and isolation of nuclei can easily damage the relatively fragile NPCs. We
      present some of the protocols we use to prepare samples for TEM and SEM to
      provide information about yeast NPC ultrastructure and the location of
      nucleoporins and transport factors by immunogold labeling within that
      ultrastructure. 

PMID- 24857726
TI  - Exploring nuclear pore complex molecular architecture by immuno-electron
      microscopy using Xenopus oocytes.
AB  - Xenopus oocytes are large in size and perfectly suited for microinjection
      experiments. Their nuclei, which can be readily isolated manually, are
      characterized by an extremely high density of nuclear pore complexes (NPCs).
      Therefore, Xenopus oocytes are an excellent system to study NPC structure and
      molecular architecture, as well as nucleocytoplasmic transport on an
      ultrastructural level. A wide range of electron microscopy (EM) techniques can be
      employed to do so and thin-sectioning immuno-EM has been proven to be a powerful
      tool in this context. NPCs are composed of multiple copies of a set of about 30
      different nucleoporins, which are often large, multidomain proteins. Their
      complex organization within NPCs can be unraveled by using domain-specific
      antibodies to individual nucleoporins in combination with microinjection and
      expression of epitope-tagged nucleoporins. Here, we describe the immuno-EM
      methods using Xenopus oocyte that allow for precise ultrastructural localization
      of nucleoporins within the structure of the NPC. 

PMID- 24857727
TI  - Utilizing the Dyn2 dimerization-zipper as a tool to probe NPC structure and
      function.
AB  - The discovery of dynein light chain 2 (Dyn2) as a member of the nucleoporins in
      yeast led to a series of applications to study NPC structure and function. Its
      intriguing ability to act as a hub for the parallel dimerization of two short
      amino acid sequence motifs (DID) prompted us to utilize it as a tool for probing
      nucleocytoplasmic transport in vivo. Further, the distinct structure of the Dyn2
      DID rod, which is easily visible in the electron microscope, allowed us to
      develop a precise structural label on proteins or protein complexes. This label
      was used to identify the position of subunits in NPC subcomplexes or to derive at
      pseudo-atomic models of single large Nups. The versatility for various
      applications of the DID-Dyn2 system makes it an attractive molecular tool beyond
      the nuclear pore and transport field. 

PMID- 24857728
TI  - The use of targeted proteomics to determine the stoichiometry of large
      macromolecular assemblies.
AB  - Accurate knowledge of the stoichiometry of protein complexes is a crucial
      prerequisite for understanding their structure and function. To purify or enrich
      large and intricate protein complexes such that their structure is preserved and
      to absolutely quantify all of their protein components is an enormous technical
      challenge. In this chapter, we describe how to purify nuclear envelopes from
      human tissue culture cells that are highly enriched for nuclear pore complexes.
      We use the nuclear pore as an example to discuss how the structural preservation
      of such preparations can be controlled. Furthermore, we give a practical guide
      how to develop and employ targeted proteomic assays for both, the absolute
      quantification of stoichiometries and the relative quantification of protein
      complex composition across multiple biological conditions. The concept discussed
      here is universally applicable to any protein complex. 

PMID- 24857729
TI  - A pulse-chase epitope labeling to study cellular dynamics of newly synthesized
      proteins: a novel strategy to characterize NPC biogenesis and ribosome
      maturation/export.
AB  - The vast number of cellular proteins performs their roles within macromolecular
      assemblies and functional cell networks. Hence, an understanding of how
      multiprotein complexes are formed and modified during biogenesis is a key problem
      in cell biology. Here, we describe a detailed protocol for a nonradioactive pulse
      chase in vivo-labeling approach. The method is based on the incorporation of an
      unnatural amino acid (O-methyl-tyrosine) by the nonsense suppression of an amber
      stop codon that quickly fuses an affinity tag of choice to a protein of interest.
      This affinity tag could be used to directly isolate the newly synthesized
      proteins and hence allows for the characterization of early complex biogenesis
      intermediates. Combined with a tetracycline controllable riboswitch in the 5'-UTR
      of the respective mRNA, this approach became a versatile tool to study dynamic
      protein assembly within cellular networks (Stelter et al., 2012). In the context
      of this volume, this method notably provides a suitable approach to study NPC,
      ribosome and mRNP biogenesis, or nuclear protein translocation. This chapter
      includes detailed protocols to track newly synthesized, epitope pulsed-chased
      proteins by western blot, their assembly within complexes using
      immunoprecipitation, and their subcellular localization using indirect
      immunofluorescence or subcellular fractionation. While these protocols use
      budding yeast as model system, this method can be adapted to other model systems.

PMID- 24857730
TI  - Analysis of nuclear reconstitution, nuclear envelope assembly, and nuclear pore
      assembly using Xenopus in vitro assays.
AB  - The large and complex eukaryotic nucleus is the arbiter of DNA replication, RNA
      transcription, splicing, and ribosome assembly. With the advent of in vitro
      nuclear reconstitution extracts derived from Xenopus eggs in the 1980s, it became
      possible to assemble multiple nuclei in vitro around added DNA or chromatin
      substrates. Such reconstituted nuclei contain a nuclear lamina, double nuclear
      membranes, nuclear pores, and are competent for DNA replication and nuclear
      import. In vitro nuclear reconstitution has allowed the assembly of "wild-type"
      and "biochemically mutant" nuclei in which the impact of individual components
      can be assessed. Here, we describe protocols for preparation of the nuclear
      reconstitution extract, nuclear reconstitution in vitro, assessment of nuclear
      membrane integrity, and a more specialized assay for nuclear pore assembly into
      preformed pore-free nuclear intermediates. 

PMID- 24857731
TI  - Xenopus in vitro assays to analyze the function of transmembrane nucleoporins and
      targeting of inner nuclear membrane proteins.
AB  - Xenopus egg extracts have been widely used to study cell cycle regulation and to
      analyze mitotic or nuclear processes on a biochemical level. Most instrumental,
      proteins of interest can be immunodepleted by specific antibodies. However, this
      approach has been restricted to non-membrane proteins, which limits its
      versatility especially when studying membrane-dependent processes such as nuclear
      envelope reformation at the end of mitosis or nuclear pore complex assembly. We
      describe here the methods developed and used in our laboratory to specifically
      remove transmembrane proteins from endogenous membranes and to insert recombinant
      integral membrane proteins into endogenous membranes. The latter procedure is
      important not only for readdition of a depleted protein in rescue experiments but
      also for introducing artificial membrane proteins such as reporters to
      investigate the passage of inner nuclear membrane proteins through nuclear pore
      complexes. 

PMID- 24857732
TI  - Imaging the assembly, structure, and function of the nuclear pore inside cells.
AB  - The nuclear pore complex (NPC) mediates selective transport across the nuclear
      envelope (NE) and plays crucial roles in several additional cellular functions.
      In higher eukaryotes, the NPC and the NE disassemble and reassemble during cell
      division and live-cell imaging has been a powerful tool to analyze these dynamic
      processes. Here, we present a method for the kinetic analysis of postmitotic NPC
      assembly and reestablishment of transport competence in intact cells by
      multicolor 4D imaging and photoswitching. By applying the methods we have
      established previously using normal rat kidney to HeLa cells, we demonstrate the
      conservation of NPC assembly in different mammalian cells. We recently showed
      that the molecular organization of the NPC can be studied by combining stochastic
      super-resolution microscopy with single-particle averaging and present this
      method here in detail. 

PMID- 24857733
TI  - Cell-fusion method to visualize interphase nuclear pore formation.
AB  - In eukaryotic cells, the nucleus is a complex and sophisticated organelle that
      organizes genomic DNA to support essential cellular functions. The nuclear
      surface contains many nuclear pore complexes (NPCs), channels for macromolecular
      transport between the cytoplasm and nucleus. It is well known that the number of
      NPCs almost doubles during interphase in cycling cells. However, the mechanism of
      NPC formation is poorly understood, presumably because a practical system for
      analysis does not exist. The most difficult obstacle in the visualization of
      interphase NPC formation is that NPCs already exist after nuclear envelope
      formation, and these existing NPCs interfere with the observation of nascent
      NPCs. To overcome this obstacle, we developed a novel system using the cell
      fusion technique (heterokaryon method), previously also used to analyze the
      shuttling of macromolecules between the cytoplasm and the nucleus, to visualize
      the newly synthesized interphase NPCs. In addition, we used a photobleaching
      approach that validated the cell-fusion method. We recently used these methods to
      demonstrate the role of cyclin-dependent protein kinases and of Pom121 in
      interphase NPC formation in cycling human cells. Here, we describe the details of
      the cell-fusion approach and compare the system with other NPC formation
      visualization methods. 

PMID- 24857734
TI  - An in vitro system to study nuclear envelope breakdown.
AB  - During mitosis in vertebrate cells, the nuclear compartment is completely
      disintegrated in the process of nuclear envelope breakdown (NEBD). NEBD comprises
      the disassembly of nuclear pore complexes, disintegration of the nuclear lamina,
      and the retraction of nuclear membranes into the endoplasmic reticulum.
      Deciphering of the mechanisms that underlie these dynamic changes requires the
      identification of the involved molecular components and appropriate experimental
      tools to define their mode of action. Here, we describe an in vitro, imaging
      based experimental system, which recapitulates NEBD. In our assay, we induce NEBD
      on nuclei of semi-permeabilized HeLa cells expressing fluorescently tagged
      nuclear envelope (NE) marker proteins by addition of mitotic cell extract that is
      supplemented with fluorescently labeled dextran. Time-lapse confocal microscopy
      is used to monitor the fate of the selected NE marker protein, and loss of the NE
      permeability barrier is deduced by influx of the fluorescent dextran into the
      nucleus. This in vitro system provides a powerful tool to follow NEBD and to
      characterize factors required for the reorganization of the NE during mitosis. 

PMID- 24857735
TI  - Modern tools to study nuclear pore complexes and nucleocytoplasmic transport in
      Caenorhabditis elegans.
AB  - The nematode Caenorhabditis elegans is characterized by many features that make
      it highly attractive to study nuclear pore complexes (NPCs) and nucleocytoplasmic
      transport. NPC composition and structure are highly conserved in nematodes and
      being amenable to a variety of genetic manipulations, key aspects of nuclear
      envelope dynamics can be observed in great details during breakdown, reassembly,
      and interphase. In this chapter, we provide an overview of some of the most
      relevant modern techniques that allow researchers unfamiliar with C. elegans to
      embark on studies of nucleoporins in an intact organism through its development
      from zygote to aging adult. We focus on methods relevant to generate loss-of
      function phenotypes and their analysis by advanced microscopy. Extensive
      references to available reagents, such as mutants, transgenic strains, and
      antibodies are equally useful to scientists with or without prior C. elegans or
      nucleoporin experience. 

PMID- 24857736
TI  - Assessing regulated nuclear transport in Saccharomyces cerevisiae.
AB  - Regulated protein transport between the cytoplasm and the nucleoplasm occurs
      through nuclear pore complexes and is critical to the function of numerous
      biological pathways. Saccharomyces cerevisiae has been used as a model system to
      probe the underlying mechanisms of nuclear transport and how they regulate
      various physiological processes. This has been facilitated, in part, by studies
      that couple the microscopic observation of a fluorescently tagged transport
      cargo's in vivo localization with numerous genetic and biochemical tools
      available to yeast researchers. Here, we describe some of these methods as they
      pertain to studies on regulated nuclear transport. 

PMID- 24857737
TI  - Analysis of nucleocytoplasmic transport in digitonin-permeabilized cells under
      different cellular conditions.
AB  - The regulation of nucleocytoplasmic transport is crucial not only for basic
      cellular activities but also for physiological adaptation to specific situation
      during the cell cycle, development, or stress. Although a wide variety of
      transport pathways have been identified in eukaryotic cells, the functional
      significance of their multiplicity remains unclear. The best-characterized
      nuclear transport receptors (NTRs) are the members of the importin beta family
      (karyopherin, transportin) whose association with specific cargoes is regulated
      by the GTPase Ran. In this chapter, we first provide an overview of the various
      expression vectors used to purify recombinant NTRs. We then describe two sets of
      recent examples of using well-established digitonin-permeabilized cell-free
      transport systems in mammalian cells to mimic different cellular conditions in
      living cells: normal/heat-shock conditions and interphase/mitosis. In the former
      case, physiological regulation impacts different transport pathways in opposite
      ways. In the latter case, the importin beta-Ran system is used at different cell
      cycle stages but with the same biochemical principle to specify the nuclear
      localization and chromatin loading of a specific protein, respectively. This in
      vitro transport assay, when adapted to specific cellular conditions or particular
      substrates, should help to uncover specific transport pathways or transport
      factors function under different cellular conditions. 

PMID- 24857738
TI  - Novel approaches for the identification of nuclear transport receptor substrates.
AB  - Nucleocytoplasmic transport affects the subcellular localization of a large
      proportion of cellular proteins. Transported proteins interact with a set of ~20
      transport receptors, importins and exportins, which mediate translocation through
      the nuclear pore complex. Here we describe two novel methods based on
      quantitative proteome analysis for the identification of cargo proteins that are
      transported by a specific importin or exportin. The first approach is based on
      SILAC (stable isotope labeling of amino acids in cells) using cells that have
      been treated or not with specific reagents, followed by subcellular
      fractionation. Applying this approach to cells treated with or without the
      selective CRM1 inhibitor leptomycin B, we identified substrates of CRM1, the
      major nuclear export receptor. In the second SILAC approach, digitonin
      permeabilized cells are incubated with nuclear and cytosolic extracts in the
      absence or presence of particular import receptors of interest. Proteomic
      analysis of the permeabilized cells then yields proteins whose nuclear import
      depends specifically on the added import receptor. Using this system, we
      identified substrates of two representative import receptors, transportin and
      importin-alpha/beta. 

PMID- 24857739
TI  - NPC mimics: probing the mechanism of nucleocytoplasmic transport.
AB  - In vitro mimics of cellular machines have been recently engineered and utilized
      to investigate processes within cells. These devices can provide novel insights
      into biological mechanisms and have the potential to improve biotechnological
      processes such as separation. In particular, several devices have been designed
      to mimic translocation through nuclear pore complexes (NPCs). We describe here
      the fabrication of a biomimetic NPC using nanoporous filters lined with FG
      repeats of proteins that create a selectivity barrier. We show the utility of
      this nanoselective filter as a testbed for the investigation of nucleocytoplasmic
      transport and demonstrate that this device closely reproduces key features of
      trafficking through the NPC. 

PMID- 24857740
TI  - Analysis of RNA transport in Xenopus oocytes and mammalian cells.
AB  - In eukaryotes, many RNA species are transcribed, processed in the nucleus, and
      exported to the cytoplasm, where they are destined to function or to be further
      matured. Some RNAs are even reimported to the nucleus. In addition, many RNAs are
      localized at specific nuclear bodies before their export and/or after their
      nuclear reimport. To understand how RNAs are transported, Xenopus oocytes are
      extremely useful cells, thanks to their large size. RNA transport can be easily
      examined by microinjecting radioactively or fluorescently labeled RNAs into
      Xenopus oocytes. Mammalian cultured cells are sometimes useful by virtue of RNA
      FISH technique. Here, we describe methods to analyze RNA localization and export
      using these cells. 

PMID- 24857741
TI  - Strategies for investigating nuclear-cytoplasmic tRNA dynamics in yeast and
      mammalian cells.
AB  - Nuclear-cytoplasmic tRNA transport involves multiple pathways that are segregated
      by the involvement of distinct proteins. The tRNA export process begins in the
      nucleolus, where the functionality of newly produced tRNAs are tested by
      aminoacylation, and ends with the delivery of the exported aminoacyl tRNAs to the
      eukaryotic elongation factor eEF-1A for utilization in protein synthesis in the
      cytoplasm. Recent studies have identified a number of proteins that participate
      in nuclear tRNA export in both yeast and mammals. However, genetic and
      biochemical evidence suggest that additional components, which have yet to be
      identified, also participate in nuclear-cytoplasmic tRNA trafficking. Here we
      review key strategies that have led to the identification and characterization of
      proteins that are involved in the nuclear tRNA export process in yeasts and
      mammals. The approaches described will greatly facilitate the identification and
      delineation of the roles of new proteins involved in nuclear export of tRNAs to
      the cytoplasm. 

PMID- 24857742
TI  - Dissecting ribosome assembly and transport in budding yeast.
AB  - Construction of the eukaryotic ribosome begins in the nucleolus and requires >300
      evolutionarily conserved nonribosomal trans-acting factors, which transiently
      associate with preribosomal subunits at distinct assembly stages. A subset of
      trans-acting and transport factors passage assembled preribosomal subunits in a
      functionally inactive state through the nuclear pore complexes (NPC) into the
      cytoplasm, where they undergo final maturation before initiating translation.
      Here, we summarize the repertoire of tools developed in the model organism
      budding yeast that are spearheading the functional analyses of trans-acting
      factors involved in the assembly and intracellular transport of preribosomal
      subunits. We elaborate on different GFP-tagged ribosomal protein reporters and a
      pre-rRNA reporter that reliably monitors the movement of preribosomal particles
      from the nucleolus to cytoplasm. We discuss the powerful yeast heterokaryon
      assay, which can be employed to uncover shuttling trans-acting factors that need
      to accompany preribosomal subunits to the cytoplasm to be released prior to
      initiating translation. Moreover, we present two biochemical approaches, namely
      sucrose gradient analyses and tandem affinity purification, that are rapidly
      facilitating the uncovering of regulatory processes that control the
      compositional dynamics of trans-acting factors on maturing preribosomal
      particles. Altogether, these approaches when combined with traditional analytical
      biochemistry, targeted proteomics and structural methodologies, will contribute
      to the dissection of the assembly and intracellular transport of preribosomal
      subunits, as well as other macromolecular assemblies that influence diverse
      biological pathways. 

PMID- 24857744
TI  - Preface. Nuclear pore complexes and nucleocytoplasmic transport-methods.

PMID- 24857743
TI  - Approaches to studying subnuclear organization and gene-nuclear pore
      interactions.
AB  - Many genes in budding yeast Saccharomyces cerevisiae associate with the nuclear
      pore complex (NPC), which impacts their location within the nucleus and their
      transcriptional regulation. To understand how eukaryotic genomes are spatially
      organized, we have used multiple approaches for analyzing the localization and
      transcription of genes. We have used these approaches to study the role of DNA
      elements in targeting genomic loci to the NPC and how these interactions regulate
      transcription, chromatin structure and the spatial organization of the yeast
      genome. These studies combine yeast molecular genetics with live-cell microscopy
      and biochemistry. Here, we present detailed protocols for these cytological and
      molecular approaches. 

PMID- 24857745
TI  - Meta-analysis of PvuII, XbaI variants in ESR1 gene and the risk of Alzheimer's
      disease: the regional European difference.
AB  - The PvuII and XbaI polymorphisms of ESR1 gene have been reported in the
      Alzheimer's disease (AD) studies. However, whether these ESR1 genetic variants
      can contribute to the risk of AD remains controversial. Herein, we conducted a
      meta-analysis to clarify the association between ESR1 polymorphisms and the
      occurrence of AD. Articles were identified by systematic searches in PubMed,
      Google scholar and Wan Fang Med Online database. The combined odds ratios (OR)
      and 95% confidence intervals (CI) were calculated within different inherited
      models. Publication bias tests, subgroup analyses and sensitive analyses were
      also performed. Overall, the PvuII variant was negatively associated with AD in
      the Caucasian population (pp vs PP+Pp, OR 0.86, 95%CI (0.76, 0.96)). However,
      there was a poor association between XbaI polymorphism and AD in European
      populations. In particular, PvuII variant was found significantly associated with
      a decreased AD risk in South European samples (pp vs PP+Pp, OR 0.86, 95%CI (0.75,
      0.98)). This meta-analysis indicated that regional European differences of ESR1
      PvuII polymorphism in the association with the occurrence of AD, which need to be
      further identified, especially in South European countries. 

PMID- 24857746
TI  - Chemical constituents of the fermentation broth of the marine-derived fungus
      Penicillium roqueforti.
AB  - BACKGROUND: The filamentous fungus Penicillium roqueforti is a well-known
      multifunctional cell factory of high added-value biomolecules. AIMS: The
      objective of this work was to carry out a detailed analysis of the metabolites
      present in the culture broth of a new marine-derived Penicillium roqueforti
      strain isolated in the Canary Islands, Spain. METHODS: The fungal biomass
      production was carried out in liquid-state fermentation, and after 10-12 days of
      incubation at 22-25 degrees C, the supernatant mycelia was separated by
      filtration, and the culture broth (12l) was stored in a refrigerator at 4 degrees
      C for a subsequent liquid-liquid extraction with dichloromethane (3*), in
      accordance with the modified Kupchan method. The volatile and semi-volatile
      organic compounds were separated by chromatography and analyzed using GC-MS and
      NMR spectroscopy analyses. RESULTS: Several volatile organic compounds involved
      in the fatty acid pathway were identified: a terpenoid, a cyclic dipeptide,
      phthalates, and an alkyl adipate. In addition, three categories of non-volatile
      compounds (alkanes, fatty acids and 1-alkanols) were identified by spectroscopy.
      The results show that the fermented broth of this fungal strain has no mycotoxins
      under the culture conditions applied. CONCLUSIONS: It is hoped that this chemo
      specific information will offer critical input for improving the biotechnological
      applications of this filamentous fungus.

PMID- 24857748
TI  - Philip Drinker.

PMID- 24857749
TI  - Human infection with MERS coronavirus after exposure to infected camels, Saudi
      Arabia, 2013.
AB  - We investigated a case of human infection with Middle East respiratory syndrome
      coronavirus (MERS-CoV) after exposure to infected camels. Analysis of the whole
      human-derived virus and 15% of the camel-derived virus sequence yielded
      nucleotide polymorphism signatures suggestive of cross-species transmission.
      Camels may act as a direct source of human MERS-CoV infection. 

PMID- 24857754
TI  - AMP-activated protein kinase activators in diabetic ulcers: from animal studies
      to Phase II drugs under investigation.
AB  - INTRODUCTION: Diagnosed cases of diabetes have gradually increased year by year,
      and research on diabetes mellitus (DM) has attracted greater attention from the
      medical profession. Diabetic ulcers present persistent pain and the risk of
      bacterial infection. However, no promising treatment methods have been found. As
      a regulator of cellular energy balance, 5' adenosine monophosphate-activated
      protein kinase (AMPK) has been suggested as a drug target for DM, including such
      drugs as metformin. AREAS COVERED: This review summarizes the current research
      and clinical trials of AMPK activators on diabetic wound healing and diabetic
      ulcers. Furthermore, it discusses the feasibility of AMPK activators in the
      treatment of diabetic wounds. EXPERT OPINION: Animal studies have demonstrated
      that AMPK activators are a potential treatment for diabetic ulcers. AMPK
      activators alleviate tissue inflammation and promote re-epithelialization in
      diabetic wounds. However, due to the complicated pathological mechanism of
      diabetic foot ulcers, AMPK activators should be combined with other approaches.
      The new strategies for combination therapy with AMPK activator may provide a
      therapeutic advantage for patients with diabetic ulcers.

PMID- 24857756
TI  - Detection of anthrax protective antigen (PA) using europium labeled anti-PA
      monoclonal antibody and time-resolved fluorescence.
AB  - Inhalation anthrax is a rare but acute infectious disease following adsorption of
      Bacillus anthracis spores through the lungs. The disease has a high fatality rate
      if untreated, but early and correct diagnosis has a significant impact on case
      patient recovery. The early symptoms of inhalation anthrax are, however, non
      specific and current anthrax diagnostics are primarily dependent upon culture and
      confirmatory real-time PCR. Consequently, there may be a significant delay in
      diagnosis and targeted treatment. Rapid, culture-independent diagnostic tests are
      therefore needed, particularly in the context of a large scale emergency
      response. The aim of this study was to evaluate the ability of monoclonal
      antibodies to detect anthrax toxin proteins that are secreted early in the course
      of B. anthracis infection using a time-resolved fluorescence (TRF) immunoassay.
      We selected monoclonal antibodies that could detect protective antigen (PA), as
      PA83 and also PA63 and LF in the lethal toxin complex. The assay reliable
      detection limit (RDL) was 6.63*10(-6)MUM (0.551ng/ml) for PA83 and 2.51*10(-5)MUM
      (1.58ng/ml) for PA63. Despite variable precision and accuracy of the assay, PA
      was detected in 9 out of 10 sera samples from anthrax confirmed case patients
      with cutaneous (n=7), inhalation (n=2), and gastrointestinal (n=1) disease.
      Anthrax Immune Globulin (AIG), which has been used in treatment of clinical
      anthrax, interfered with detection of PA. This study demonstrates a culture
      independent method of diagnosing anthrax through the use of monoclonal antibodies
      to detect PA and LF in the lethal toxin complex.

PMID- 24857757
TI  - MNV primarily surveillance by a recombination VP1-derived ELISA in Beijing area
      in China.
AB  - Murine norovirus (MNV) was first found as a surrogate for human norovirus study.
      However, MNV infection was mostly prevalent in laboratory mice, and its
      immunomodulatory properties may affect the outcome of animal experiments. MNV
      surveillance had been performed in Europe, North America and some other
      countries, but not in China. Nowadays, the complete MNV virions had been used as
      antigen in MNV serological detection. However, the complexity in the preparation
      of virions might affect the antigen stability, and the virulence recovery of
      virion antigen had also been detected. In this study, the caspid VP1 protein was
      proved to be the mostly predominant antigen in MNV virions. An ELISA method using
      the recombination VP1 as antigen was developed (rVP1 ELISA). The rVP1 ELISA is
      more sensitive and less specific than the MNV virion-derived IFA method. To
      address the prevalence of MNV in China, a totally 600 mouse serum samples from
      Beijing area were tested by rVP1 ELISA and confirmed by IFA and WB. The MNV
      infection rate was 11.67%, but most of the MNV-positive samples were from
      experimental facilities (MNV rate=30.94%), not from commercial vendors (MNV
      rate=0.27%). Collectively, a sensitive rVP1 ELISA was developed in the current
      study, and the MNV investigation by rVP1 ELISA showed that MNV infection was
      mostly prevalent in the laboratory mice, especially the mice from experimental
      facilities in Beijing area in China.

PMID- 24857755
TI  - Comparative analysis of the efficiency and specificity of myeloid-Cre deleting
      strains using ROSA-EYFP reporter mice.
AB  - Since the first example of conditional gene targeting in mice in 1994, the use of
      Cre recombinase and loxP flanked sequences has become an invaluable technique to
      generate tissue and temporal specific gene knockouts. The number of mouse strains
      expressing floxed-gene sequences, and tissue-specific or temporal-specific Cre
      recombinase that have been reported in the literature has grown exponentially.
      However, increased use of this technology has highlighted several problems that
      can impact the interpretation of any phenotype observed in these mouse models. In
      particular, accurate knowledge of the specificity of Cre expression in each
      strain is critical in order to make conclusions about the role of specific cell
      types in the phenotypes observed. Cre-mediated deletion specificity and
      efficiency have been described in many different ways in the literature, making
      direct comparisons between these Cre strains impossible. Here we report crossing
      thirteen different myeloid-Cre mouse strains to ROSA-EYFP reporter mice and
      assaying YFP expression in a variety of naive unstimulated hematopoietic cells,
      in parallel. By focusing on myeloid subsets, we directly compare the relative
      efficiency and specificity of myeloid deletion in these strains under steady
      state conditions. 

PMID- 24857747
TI  - Functional interactions among members of the MAX and MLX transcriptional network
      during oncogenesis.
AB  - The transcription factor MYC and its related family members MYCN and MYCL have
      been implicated in the etiology of a wide spectrum of human cancers. Compared to
      other oncoproteins, such as RAS or SRC, MYC is unique because its protein coding
      region is rarely mutated. Instead, MYC's oncogenic properties are unleashed by
      regulatory mutations leading to unconstrained high levels of expression. Under
      both normal and pathological conditions MYC regulates multiple aspects of
      cellular physiology including proliferation, differentiation, apoptosis, growth
      and metabolism by controlling the expression of thousands of genes. How a single
      transcription factor exerts such broad effects remains a fascinating puzzle.
      Notably, MYC is part of a network of bHLHLZ proteins centered on the MYC
      heterodimeric partner MAX and its counterpart, the MAX-like protein MLX. This
      network includes MXD1-4, MNT, MGA, MONDOA and MONDOB proteins. With some
      exceptions, MXD proteins have been functionally linked to cell cycle arrest and
      differentiation, while MONDO proteins control cellular metabolism. Although the
      temporal expression patterns of many of these proteins can differ markedly they
      are frequently expressed simultaneously in the same cellular context, and
      potentially bind to the same, or similar DNA consensus sequence. Here we review
      the activities and interactions among these proteins and propose that the broad
      spectrum of phenotypes elicited by MYC deregulation is intimately connected to
      the functions and regulation of the other network members. Furthermore, we
      provide a meta-analysis of TCGA data suggesting that the coordinate regulation of
      the network is important in MYC driven tumorigenesis. This article is part of a
      Special Issue entitled: Myc proteins in cell biology and pathology. 

PMID- 24857758
TI  - Effect of quercetin and rutin in some acute seizure models in mice.
AB  - Quercetin is one of the most widely occurring flavonoid which is also often
      present in plants as glycosidic form - rutin. These compounds are ingredients of
      plant diet and are also present in numerous pharmaceutical preparations and diet
      supplements which are taken by patients suffering from epilepsy and treating with
      antiepileptic drugs (AEDs). Influence of these compounds on central nervous
      system-related effects was proved both in experimental and clinical studies.
      Their influence on anxiety, depression, memory processes and convulsant activity
      was reported. The aim of the present study was to investigate the effect of
      quercetin and rutin in some models of seizures, i.e., in the model of psychomotor
      seizures induced by 6Hz stimulation, in the maximal electroshock seizure
      threshold and intravenous pentylenetetrazole tests in mice. We also examined a
      possible mechanism of anticonvulsant activity of quercetin and its influence on
      action of two AEDs, i.e., valproic acid and levetiracetam, in the 6Hz seizure
      test. Our results revealed only a weak anticonvulsant potential of the studied
      flavonoids because they showed anticonvulsant action at doses from 10 to 200mg/kg
      only in the 6Hz test and did not change seizure thresholds in the remaining
      tests. Moreover, anticonvulsant action of the studied flavonoids was short-term,
      noted only at pretreatment time ranging between 30 and 60min. The highest
      anticonvulsant activity of quercetin was correlated with its high plasma and
      brain concentration, which was revealed in a pharmacokinetic study. We did not
      note changes in the anticonvulsant action of the used AEDs combined with
      quercetin in the model of psychomotor seizures in mice. Neither quercetin and
      rutin nor combinations of quercetin with the studied AEDs produced any
      significant impairments of motor coordination (assessed in the chimney test),
      muscular strength (investigated in the grip-strength test) and long-term memory
      (evaluated in the passive avoidance test) in mice. The results of the present
      study suggest that quercetin and rutin have only weak and short-term
      anticonvulsant potential. These flavonoids seem to be safe for patients with
      epilepsy because they neither changed activity of the studied AEDs nor produced
      any adverse effects. 

PMID- 24857760
TI  - Prevalence of MR imaging abnormalities in vitamin B12 deficiency patients
      presenting with clinical features of subacute combined degeneration of the spinal
      cord.
AB  - BACKGROUND AND AIMS: Subacute combined degeneration (SACD) of the spinal cord,
      characterized by degeneration of lateral and posterior columns, is often found in
      vitamin B12 deficiency. Our aim was to look for sensitivity of imaging in
      depicting the spinal cord abnormality in vitamin B12 deficient patients and to
      find any correlation of vitamin B12 levels with clinical scores/severity at time
      of presentation. MATERIAL AND METHODS: A total 54 patients with biochemically
      proven vitamin B12 deficiency were included in the study. In all these patients
      MR study of cervico-dorsal spine was done. All the patients after initiation of
      appropriate treatment were followed up for a minimum of two months. RESULTS: MRI
      showed cord signal abnormality in only 8 patients out of 54 patients with low
      sensitivity of 14.8%. After appropriate therapy, complete resolution of cord
      signal abnormalities was observed in all these 8 patients, on follow-up MR
      imaging. Significant negative correlation (r=-0.503, p<0.000) was seen between
      the clinical severity scores and initial vitamin B12 levels. CONCLUSION:
      Conventional MRI may not be a useful tool for the diagnosis of SACD as it has
      very low sensitivity. Inverse correlation of Vitamin B12 levels with clinical
      scoring suggests that initial serum vitamin B12 levels may help in predicting the
      clinical severity.

PMID- 24857759
TI  - Lateralization of temporal lobe epilepsy using a novel uncertainty analysis of MR
      diffusion in hippocampus, cingulum, and fornix, and hippocampal volume and FLAIR
      intensity.
AB  - PURPOSE: To analyze the utility of a quantitative uncertainty analysis approach
      for evaluation and comparison of various MRI findings for the lateralization of
      epileptogenicity in mesial temporal lobe epilepsy (mTLE), including novel
      diffusion-based analyses. METHODS: We estimated the hemispheric variation
      uncertainty (HVU) of hippocampal T1 volumetry and FLAIR (Fluid Attenuated
      Inversion Recovery) intensity. Using diffusion tensor images of 23 nonepileptic
      subjects, we estimated the HVU levels of mean diffusivity (MD) in the
      hippocampus, and fractional anisotropy (FA) in the posteroinferior cingulum and
      crus of fornix. Imaging from a retrospective cohort of 20 TLE patients who had
      undergone surgical resection with Engel class I outcomes was analyzed to
      determine whether asymmetry of preoperative volumetrics, FLAIR intensities, and
      MD values in hippocampi, as well as FA values in posteroinferior cingula and
      fornix crura correctly predicted laterality of seizure onset. Ten of the cohort
      had pathologically proven mesial temporal sclerosis (MTS). Seven of these
      patients had undergone extraoperative electrocorticography (ECoG) for
      lateralization or to rule out extra-temporal foci. RESULTS: HVU was estimated to
      be 3.1*10(-5) for hippocampal MD, 0.027 for FA in posteroinferior cingulum, 0.018
      for FA in crus of fornix, 0.069 for hippocampal normalized volume, and 0.099 for
      hippocampal normalized FLAIR intensity. Using HVU analysis, a higher hippocampal
      MD value, lower FA within the posteroinferior cingulum and crus of fornix,
      shrinkage in hippocampal volume, and higher hippocampal FLAIR intensity were
      observed beyond uncertainty on the side ipsilateral to seizure onset for 10, 10,
      9, 9, and 10 out of 10 pathology-proven MTS patients, respectively. Considering
      all 20 TLE patients, these numbers were 18, 15, 14, 13, and 16, respectively.
      However, consolidating the lateralization results of HVU analysis on these
      quantities by majority voting has detected the epileptogenic side for 19 out of
      20 cases with no wrong lateralization. CONCLUSION: The presence of MTS in TLE
      patients is associated with an elevated MD value in the ipsilateral hippocampus
      and a reduced FA value in the posteroinferior subregion of the ipsilateral
      cingulum and crus of ipsilateral fornix. When considering all TLE patients, among
      the mentioned biomarkers the hippocampal MD had the best performance with true
      detection rate of 90% without any wrong lateralization. The proposed uncertainty
      based analyses hold promise for improving decision-making for surgical resection.

PMID- 24857761
TI  - Association of intracranial pressure with outcome in comatose patients with
      intracerebral hemorrhage.
AB  - BACKGROUND: Therapeutic targets for intracranial pressure (ICP) in patients with
      severe intracerebral hemorrhage (ICH) are approximated from data of traumatic
      brain injury. However, specific data for ICH are lacking. Here, we aimed to
      investigate the association between ICP, mortality and functional outcome
      following severe ICH. METHODS: We analyzed consecutive comatose patients with ICH
      in whom ICP monitoring was applied. Outcome at 3 months was assessed using the
      modified Rankin scale (mRS). Multivariate logistic regression including pre
      defined predictors was used in order to identify the effects of ICP on outcome.
      RESULTS: 121 patients with ICH and ICP monitoring were analyzed. Mean ICP (OR
      1.2, CI 1.08-1.45, p=0.003), ICP variability (OR 1.3, CI 1.03-1.73, p=0.03) and
      relative frequency of ICP values >20 mm Hg (OR 1.1, CI 1.02- 1.15, p=0.008) were
      independently associated with mortality at 3 months. Relative frequency of ICP
      values >20 mm Hg (OR 1.1, CI 1.001-1.3, p=0.04) was associated also with poor
      functional outcome at 3 months. CONCLUSIONS: Our data suggest that in the context
      of other predictors as age, admission clinical status, hemorrhage volume and
      intraventricular hemorrhage, average ICP, ICP variability and the frequency of
      ICP values >20 mm Hg are independently associated with mortality and poor outcome
      after ICH. Further studies and prospective validations of ICP thresholds for ICH
      patients are highly warranted.

PMID- 24857763
TI  - Sulfated glycosaminoglycan-based block copolymer: preparation of biocompatible
      chondroitin sulfate-b-poly(lactic acid) micelles.
AB  - Despite a growing interest in amphiphilic polysaccharide-based diblock copolymers
      as functional polymeric drug delivery nanosystems, biologically relevant sulfated
      glycosaminoglycan systems were not yet investigated. Here, we report the
      synthesis and the self-assembly properties in water of chondroitin sulfate-b
      poly(lactic acid) (CS-b-PLA(n)). The CS-b-PLA(n) were synthesized using click
      grafting onto method implying reducing-end alkynation of low-molecular weight
      depolymerized CS (M(w) = 5000 g.mol(-1)) and azide-terminated functionalization
      of PLAn (M(w) = 6500 g.mol(-1) (n = 46) and M(w) = 1700 g.mol(-1) (n = 20)). The
      diblock copolymer self-assembled in water giving rise to spherical micelles that
      were characterized in solution using dynamic/static light scattering and at dry
      state by TEM technique. In vitro assays on healthy cells showed that at high
      concentrations, up to 10 MUg.mL(-1), CS-b-PLA(n) were noncytotoxic. Those
      preliminary studies are promising in the perspective to use them as biocompatible
      nanovehicles for anticancer drug delivery.

PMID- 24857764
TI  - Genetic relatedness of dolphin rhabdovirus with fish rhabdoviruses.

PMID- 24857766
TI  - Enhanced electrochemical performance with surface coating by reactive magnetron
      sputtering on lithium-rich layered oxide electrodes.
AB  - Electrode films fabricated with lithium-rich layered 0.3Li2MnO3
      0.7LiNi5/21Co5/21Mn11/21O2 cathode materials have been successfully modified with
      ZnO coatings via a reactive magnetron sputtering (RMS) process for the first
      time. The morphology and chemical composition of coating films on the electrodes
      have been in deep investigated by transmission electron microscopy (TEM), energy
      dispersive spectrometry (EDS), and X-ray photoelectron spectroscopy (XPS)
      characterizations. The results clearly demonstrate that ZnO film coatings are
      ultrathin, dense, uniform, and fully covered on the electrodes. The RMS-2 min
      (deposition time) coated electrode exhibits much higher initial discharge
      capacity and coulombic efficiency with 316.0 mAh g(-1) and 89.1% than that of the
      pristine electrode with 283.4 mAh g(-1) and 81.7%. In addition, the discharge
      capacity also reaches 256.7 and 187.5 mAh g(-1) at 0.1 and 1.0 C-rate, as
      compared to that of 238.4 and 157.8 mAh g(-1) after 50 cycles. The improved
      electrochemical performances of RMS-coated electrodes are ascribed to the high
      quality ZnO film coatings that reduce charge transfer resistance and effectively
      protect active material from electrolyte oxidation. 

PMID- 24857767
TI  - Leukocyte phagocytosis and lysozyme activity in Nile tilapia fed supplemented
      diet with natural extracts of propolis and Aloe barbadensis.
AB  - Although there is evidence on the benefits in the use of immunostimulants in
      aquaculture, there are few commercial products being used. This study evaluated
      the use of natural substances as potential sources for the production of
      immunostimulants. Propolis and Aloe barbadensis have been widely studied and its
      extracts have different chemical constituents responsible for antimicrobial, anti
      inflammatory and immunostimulant. Tilapia juveniles were fed for two weeks with
      diets supplemented mix of propolis extracts and aloe (1:1) in different
      concentrations: 0.5, 1 e 2%. After the experimental period, fish blood was
      collected for hematoimmunological as follows : hematocrit, total plasma protein,
      erythrocytes (RBC), leukocytes (WBC), differential leukocyte count, phagocytic
      activity, serum lysozyme activity, and serum antimicrobial activity, serum
      antimicrobial activity (evaluated against Aeromonas hydrophila, Enterococcus
      durans and Escherichia coli). Except for higher number of thrombocytes in 1%
      supplemented fish, the rest did not show significant difference.

PMID- 24857768
TI  - Subjective visual vertical in Pisa syndrome.
AB  - BACKGROUND: Parkinson's Disease (PD) alters perception and somatosensory
      information integration, including visual dependency and judgment of body
      position in space. PD may be associated with Pisa syndrome (PS), a lateral
      deviation of the longitudinal body axis (LBA) of unknown origin. We tested
      whether this inclination is associated with an altered perception of the
      subjective visual vertical (SVV) and if these alterations are secondary effects
      of the LBA deviation or of a primary perceptual dysfunction. Furthermore, we
      investigated the contribution of different sensory modalities and dopaminergic
      medication. METHODS: Seventeen PD patients (8 with PS, 9 without PS) and 18
      healthy controls were tested. The SVV was assessed in a seated, in a lateral
      horizontal and - in PS patients - in a seated manually rectified position. Frame
      and moving-stimulus-patterns were used to test visual dependency. In PD and PS
      patients all trials were conducted in dopaminergic "on" and "off". RESULTS: When
      seated, SVV values on PD in "on" and PS in "on" and "off" differed significantly
      from controls. This difference remained in PS patients after manual rectification
      in "off". The SVV in a lateral horizontal position was not significantly
      different between the three groups. When inclined, visual dependency was higher
      in PD "off" than in controls. DISCUSSION: Both PS and PD patients showed SVV
      deviations compared to healthy controls. These cannot be explained by their
      intrinsic lateral deviation in PS patients. They must be secondary to either a
      primary perceptual dysfunction or alterations of internal models of verticality
      due to re-weighting of perceptual afferences.

PMID- 24857769
TI  - Assessing speech dysfunction using BOLD and acoustic analysis in parkinsonism.
AB  - INTRODUCTION: Speech dysfunction is often associated with parkinsonism
      (Parkinson's disease (PD), Multiple System Atrophy (MSA), and Progressive
      Supranuclear Palsy (PSP)), along with characteristic motor features. Any or all
      of the following i.e. respiratory, phonatory, resonatory, or articulatory
      components of speech production may be affected. Articulatory imprecision,
      repetition of syllables (tachyphrenia), and tremor of oropharyngeal structures
      add to speech unintelligibility. We studied acoustics using spectrogram and its
      correlation with BOLD activation during voice/speech production across these
      subjects. METHODS: BOLD studies were conducted on 108 subjects (29 PD, 20 MSA and
      19 PSP and 40 controls) on 1.5 T MR scanner using 130 dynamics. Active phase
      involved acquisition (10 volumes each) of audible reading of visually presented
      bi-syllabic meaningful Hindi simple words (5 types of non-nasal stop consonant
      categories, i.e. namely velars, palatals, retroflexes, dentals, bilabials and one
      nasal stop consonant) with interleaved silence during baseline. The subjects'
      voice samples were analyzed for acoustic parameters, namely formant frequencies
      of the adjoining vowels, voice onset time (VOT), and intensities using
      spectrogram. Correlation of BOLD activation in different brain areas with
      acoustic parameters was evaluated. RESULTS: Voice intensity was significantly
      lowered, while VOTs were delayed in these patients as compared to healthy
      controls. All acoustic parameters were significantly affected for nasal
      consonants. BOLD activation correlated positively in primary motor cortex to
      VOTs, while F2 formants to activation of supplementary motor area. CONCLUSION:
      The differences in the acoustic quality of various stop consonants in patients
      may be helpful in differentiating these three parkinsonian disorders.

PMID- 24857770
TI  - Molecular cloning and characterization of a novel heat shock protein 20 of
      Babesia orientalis.
AB  - The heat shock protein 20 (HSP20) gene of Babesia orientalis (BoHSP20) was
      identified from both genomic DNA and cDNA. The full-length BoHSP20 gene was 690bp
      with one intron from position 88-243bp. The amplicon obtained from cDNA
      corresponded to a full-length open reading frame (ORF) with a length of 534bp,
      encoding a polypeptide of 178 amino acid residues with a predicted size of 20kDa.
      The ORF was cloned into a pET-28a plasmid and subsequently expressed as a His
      fusion protein. The recombinant HSP20 of B. orientalis (rBoHSP20) was purified
      and evaluated as an antigen using Western blotting. Anti-B. orientalis water
      buffalo serum reacted with rBoHSP20, indicating that this protein was an
      immunodominant antigen and could be a useful diagnostic reagent to detect
      antibodies against B. orientalis in water buffalo. The native BoHSP20 was
      recognized by polyclonal antibody from the serum of rabbit immunized with
      rBoHSP20. Strong immunofluorescence signals were observed from B. orientalis in
      blood smears by fluorescence microscopy. Bacterial survival experiments indicated
      that HSP20 can significantly increase the viability of bacteria when the culture
      is exposed to thermal stress. The results suggest that BoHSP20 might play an
      important role during B. orientalis transmission from tick to host animal, given
      the sudden shifts in temperature involved. Phylogenetic analysis revealed that B.
      orientalis is in the Babesia clade and most closely related to Babesia bovis.
      Similar topologies were obtained from trees based on 18S rRNA and the HSP70 gene.
      The present study suggests that BoHSP20 might be a potential diagnostic antigen
      and that the HSP20 genes can aid in the classification of Babesia and Theileria
      species. 

PMID- 24857771
TI  - Use of pelleted sericea lespedeza (Lespedeza cuneata) for natural control of
      coccidia and gastrointestinal nematodes in weaned goats.
AB  - Infection with Eimeria spp. (coccidia) can be devastating in goats, particularly
      for young, recently-weaned kids, resulting in diarrhea, dehydration, and even
      death. Feeding dried sericea lespedeza [SL; Lespedeza cuneata (Dum.-Cours.) G.
      Don.] to young goats has been reported to reduce the effects of internal
      parasites, including gastrointestinal nematodes (GIN) but there have been no
      reports of the effects of feeding this forage on Eimeria spp. in goats. Two
      confinement feeding experiments were completed on recently-weaned intact bucks
      (24 Kiko-cross, Exp. 1; 20 Spanish, Exp. 2) to determine effects of SL pellets on
      an established infection of GIN and coccidia. The bucks were assigned to 1 of 2
      (Exp. 1) or 3 (Exp. 2) treatment groups based upon the number of Eimeria spp.
      oocysts per gram (OPG) of feces. In Exp. 1, the kids were fed 1 of 2 pelleted
      rations ad libitum; 90% SL leaf meal+10% of a liquid molasses/lignin binder mix
      and a commercial pellet with 12% crude protein (CP) and 24% acid detergent fiber
      (n=12/treatment group, 2 animals/pen). For Exp. 2, treatment groups were fed (1)
      90% SL leaf meal pellets from leaves stored 3 years (n=7), (2) 90% SL pellets
      from leaf meal stored less than 6 months, (n=7), and the commercial pellets (n=6)
      ad libitum. For both trials, fecal and blood samples were taken from individual
      animals every 7 days for 28 days to determine OPG and GIN eggs per gram (EPG) and
      packed cell volume (PCV), respectively. In Exp. 2, feces were scored for
      consistency (1=solid pellets, 5=slurry) as an indicator of coccidiosis. In Exp.
      1, EPG (P<0.001) and OPG (P<0.01) were reduced by 78.7% and 96.9%, respectively,
      7 days after initiation of feeding in goats on the SL pellet diet compared with
      animals fed the control pellets. The OPG and EPG remained lower in treatment than
      control animals until the end of the trial. In Exp. 2, goats fed new and old SL
      leaf meal pellets had 66.2% and 79.2% lower (P<0.05) EPG and 92.2% and 91.2%
      lower (P<0.05) OPG, respectively, than control animals within 7 days, and these
      differences were maintained or increased throughout the trial. After 4 weeks of
      pellet feeding in Exp. 2, fecal scores were lower (P<0.01) in both SL-fed groups
      compared with control animals, indicating fewer signs of coccidiosis. There was
      no effect of diet on PCV values throughout either experiment. Dried, pelleted SL
      has excellent potential as a natural anti-coccidial feed for weaned goats. 

PMID- 24857772
TI  - Percutaneous excretion of iron and ferritin (through Al-hijamah) as a novel
      treatment for iron overload in beta-thalassemia major, hemochromatosis and
      sideroblastic anemia.
AB  - Iron overload is a big challenge when treating thalassemia (TM), hemochromatosis
      and sideroblastic anemia. It persists even after cure of TM with bone marrow
      transplantation. Iron overload results from increased iron absorption and
      repeated blood transfusions causing increased iron in plasma and interstitial
      fluids. Iron deposition in tissues e.g. heart, liver, endocrine glands and others
      leads to tissue damage and organ dysfunction. Iron chelation therapy and
      phlebotomy for iron overload have treatment difficulties, side effects and
      contraindications. As mean iron level in skin of TM patients increases by more
      than 200%, percutaneous iron excretion may be beneficial. Wet cupping therapy
      (WCT) is a simple, safe and economic treatment. WCT is a familiar treatment
      modality in some European countries and in Chinese hospitals in treating
      different diseases. WCT was reported to clear both blood plasma and interstitial
      spaces from causative pathological substances (CPS). Standard WCT method is Al
      hijamah (cupping, puncturing and cupping, CPC) method of WCT that was reported to
      clear blood and interstitial fluids better than the traditional WCT (puncturing
      and cupping method, PC method of WCT). In other word, traditional WCT may be
      described as scarification and suction method (double S technique), while Al
      hijamah may be described as suction, scarification and suction method (triple S
      technique). Al-hijamah is a more comprehensive treatment modality that includes
      all steps and therapeutic benefits of traditional dry cupping therapy and WCT
      altogether according to the evidence-based Taibah mechanism (Taibah theory).
      During the first cupping step of Al-hijamah, a fluid mixture is collected inside
      skin uplifting due to the effect of negative pressure inside sucking cups. This
      fluid mixture contains collected interstitial fluids with CPS (iron, ferritin and
      hemolyzed RBCs in thalassemia), filtered fluids (from blood capillaries) with
      iron and hemolyzed blood cells (hemolyzed RBCs, WBCs and platelets). That fluid
      mixture does not contain intact blood cells (having diameters in microns) that
      are too big to pass through pores of skin capillaries (6-12nm in diameter) and
      cannot be filtered. Puncturing skin upliftings and applying second cupping step
      excrete collected fluids. Skin scarifications (shartat mihjam in Arabic) should
      be small, superficial (0.1mm in depth), short (1-2mm in length), multiple, evenly
      distributed and confined to skin upliftings. Sucking pressure inside cups (-150
      to -420mmHg) applied to skin is transmitted to around skin capillaries to be
      added to capillary hydrostatic pressure (-33mmHg at arterial end of capillaries
      and -13mmHg at venous end of capillaries) against capillary osmotic pressure
      (+20mmHg). This creates a pressure gradient and a traction force across skin and
      capillaries and increases filtration at arterial end of capillaries at net
      pressure of -163 to -433mmHg and at venous end of capillaries at net pressure of 
      143 to -413mmHg resulting in clearance of blood from CPS (iron, ferritin and
      hemolyzed blood cells). Net filtration pressure at renal glomeruli is 10mmHg i.e.
      Al-hijamah exerts a more pressure-dependent filtration than renal glomeruli. Al
      hijamah may benefit patients through inducing negative iron balance.
      Interestingly, Al-hijamah was reported to decrease serum ferritin significantly
      (by about 22%) in healthy subjects while excessive traditional WCT was reported
      to cause iron deficiency anemia. Al-hijamah is a highly recommended treatment in
      prophetic medicine. In conclusion, Al-hijamah may be a promising adjuvant
      treatment for iron overload in TM, hemochromatosis and sideroblastic anemia. 

PMID- 24857773
TI  - Selection and characterization of DNA aptamers specific for Listeria species.
AB  - Single-stranded (ss) DNA aptamers with binding affinity to Listeria spp. were
      selected using a whole-cell SELEX (Systematic Evolution of Ligands by EXponential
      enrichment) method. Listeria monocytogenes cells were grown at 37 degrees C and
      harvested at mid-log phase or early stationary phase to serve as the targets in
      SELEX. A total of 10 unique aptamer sequences were identified, six associated
      with log phase cells and four with stationary phase cells. Binding affinity of
      the aptamers was determined using flow cytometry and ranged from 10% to 44%. Four
      candidates having high binding affinity were further studied and found to show
      genus-specific binding affinity when screened against five different species
      within the Listeria genus. Using sequential binding assays combined with flow
      cytometry, it was determined that three of the aptamers (LM6-2, LM12-6, and LM12
      13) bound to one apparent cell surface moiety, while a fourth aptamer (LM6-116)
      appeared to bind to a different cell surface region. This is the first study in
      which SELEX targeted bacterial cells at different growth phases. When used
      together, aptamers that bind to different cell surface moieties could increase
      the analytical sensitivity of future capture and detection assays. 

PMID- 24857774
TI  - AlphaLISA-based high-throughput screening assay to measure levels of soluble
      amyloid precursor protein alpha.
AB  - Activation of nonamyloidogenic processing of amyloid precursor protein (APP) has
      been hypothesized to be a viable approach for Alzheimer's disease drug discovery.
      However, until recently, the lack of HTS-compatible assay technologies precluded
      large scale screening efforts to discover molecules that potentiate
      nonamyloidogenic pathways. We have developed an HTS-compatible assay based on
      AlphaLISA technology that quantitatively detects soluble APPalpha (sAPPalpha), a
      marker of nonamyloidogenic processing of APP, released from live cells in low
      volume, 384-well plates. The assay exhibited good QC parameters (Z'>0.5, S/B>2).
      A pilot screen of 801 compounds yielded a novel chemotype that increased the
      release of sAPPalpha 2-fold at 5MUM. These results suggest that the AlphaLISA
      based HTS assay is robust and sensitive and can be used to screen large compound
      collections to discover molecules that potentiate the release of sAPPalpha.
      Additionally, we demonstrated that increase of APP processing by nonamyloidogenic
      pathways will result in decrease of release of amyloidogenic Abeta40 fragments. 

PMID- 24857775
TI  - Design and synthesis of fluorescent probes for GPR54.
AB  - Kisspeptins are neuropeptides that induce the secretion of gonadotropin-releasing
      hormone via the activation of the cognate receptor, G-protein coupled receptor 54
      (GPR54). The kisspeptin-GPR54 axis is associated with the onset of puberty and
      the maintenance of the reproductive system. In this study, several fluorescent
      probes have been designed and synthesized for rat GPR54 through the modification
      of the N-terminus of rat kisspeptins to allow for the visualization of the
      expression and localization of kisspeptin receptor(s) in living cells and native
      tissues. The tetramethylrhodamine (TMR) and rhodamine green (RG)-labeled
      kisspeptins exhibited good binding and agonistic activities towards GPR54, and
      the results of the application studies demonstrated that these fluorescent probes
      could be used effectively for the detection of GPR54 receptors in flow cytometry
      and confocal microscopy experiments. 

PMID- 24857777
TI  - Design, synthesis and biological evaluation of hydroxy- or methoxy-substituted 5
      benzylidene(thio) barbiturates as novel tyrosinase inhibitors.
AB  - Here a new class of hydroxy- or methoxy-substituted 5
      benzylidene(thio)barbiturates were designed, synthesized and their inhibitory
      effects on the diphenolase activity of mushroom tyrosinase were evaluated. The
      results showed that several compounds had more potent tyrosinase inhibitory
      activities than the widely used tyrosinase inhibitor kojic acid (IC50=18.25MUM).
      In particular, 3',4'-dihydroxylated 1e was found to be the most potent inhibitor
      with IC50 value of 1.52MUM. The inhibition mechanism analysis revealed that the
      potential compounds 1e and 2e exhibited such inhibitory effects on tyrosinase by
      acting as the irreversible inhibitors. Structure-activity relationships' (SARs)
      analysis also suggested that further development of such compounds might be of
      interest. 

PMID- 24857776
TI  - Synthesis and antimalarial activity of metal complexes of cross-bridged
      tetraazamacrocyclic ligands.
AB  - Using transition metals such as manganese(II), iron(II), cobalt(II), nickel(II),
      copper(II), and zinc(II), several new metal complexes of cross-bridged
      tetraazamacrocyclic chelators namely, cyclen- and cyclam-analogs with benzyl
      groups, were synthesized and screened for in vitro antimalarial activity against
      chloroquine-resistant (W2) and chloroquine-sensitive (D6) strains of Plasmodium
      falciparum. The metal-free chelators tested showed little or no antimalarial
      activity. All the metal complexes of the dibenzyl cross-bridged cyclam ligand
      exhibited potent antimalarial activity. The Mn(2+) complex of this ligand was the
      most potent with IC50s of 0.127 and 0.157MUM against the chloroquine-sensitive
      (D6) and chloroquine-resistant (W2) P. falciparum strains, respectively. In
      general, the dibenzyl hydrophobic ligands showed better anti-malarial activity
      compared to the activity of monobenzyl ligands, potentially because of their
      higher lipophilicity and thus better cell penetration ability. The higher
      antimalarial activity displayed by the manganese complex for the cyclam ligand in
      comparison to that of the cyclen, correlates with the larger pocket of cyclam
      compared to that of cyclen which produces a more stable complex with the Mn(2+).
      Few of the Cu(2+) and Fe(2+) complexes also showed improvement in activity but
      Ni(2+), Co(2+) and Zn(2+) complexes did not show any improvement in activity upon
      the metal-free ligands for anti-malarial development. 

PMID- 24857779
TI  - A class of phase-transfer catalyst with interionic strain: insight into the
      bonding of disubstituted N- vs carbene-stabilized N(I)-centered cations.
AB  - The straightforward synthesis of a class of nitrogen-based phase-transfer
      catalysts (PTCs) having markedly dissociated anions due to interionic donor-donor
      "ion pair strain" and use for catalyzing benzylation and benzylic fluorination is
      reported. Provided also is insight into the bonding of disubstituted N- vs so
      called divalent carbene-stablized N(I)-centered cations and the unprecedented
      finding of a cyclopropenium based C-H...piaryl interaction. 

PMID- 24857780
TI  - In vivo effects of synthetic cannabinoids JWH-018 and JWH-073 and
      phytocannabinoid Delta9-THC in mice: inhalation versus intraperitoneal injection.
AB  - Human users of synthetic cannabinoids (SCBs) JWH-018 and JWH-073 typically smoke
      these drugs, but preclinical studies usually rely on injection for drug delivery.
      We used the cannabinoid tetrad and drug discrimination to compare in vivo effects
      of inhaled drugs with injected doses of these two SCBs, as well as with the
      phytocannabinoid Delta(9)-tetrahydrocannabinol (Delta(9)-THC). Mice inhaled
      various doses of Delta(9)-THC, JWH-018 or JWH-073, or were injected
      intraperitoneally (IP) with these same compounds. Rectal temperature, tail flick
      latency in response to radiant heat, horizontal bar catalepsy, and suppression of
      locomotor activity were assessed in each animal. In separate studies, mice were
      trained to discriminate Delta(9)-THC (IP) from saline, and tests were performed
      with inhaled or injected doses of the SCBs. Both SCBs elicited Delta(9)-THC-like
      effects across both routes of administration, and effects following inhalation
      were attenuated by pretreatment with the CB1 antagonist/inverse agonist
      rimonabant. No cataleptic effects were observed following inhalation, but all
      compounds induced catalepsy following injection. Injected JWH-018 and JWH-073
      fully substituted for Delta(9)-THC, but substitution was partial (JWH-073) or
      required relatively higher doses (JWH-018) when drugs were inhaled. These studies
      demonstrate that the SCBs JWH-018 and JWH-073 elicit dose-dependent, CB1 receptor
      mediated Delta(9)-THC-like effects in mice when delivered via inhalation or via
      injection. Across these routes of administration, differences in cataleptic
      effects and, perhaps, discriminative stimulus effects, may implicate the
      involvement of active metabolites of these compounds. 

PMID- 24857781
TI  - Cytokine regulation by epidermal growth factor receptor inhibitors and epidermal
      growth factor receptor inhibitor associated skin toxicity in cancer patients.
AB  - AIM: Epidermal growth factor receptor inhibitor (EGFRI) induced skin toxicity has
      a prognostic value suggesting skin toxicity can be a useful surrogate marker for
      successful epidermal growth factor receptor (EGFR) inhibition, improved response
      and survival. But the pathophysiology of EGFRI induced skin toxicity remains
      elusive. However the involvement of immunological mechanisms has been speculated.
      This study investigates the possible underlying mechanism of EGFR inhibition
      associated cytokine production in keratinocytes as well as in patients after
      treatment with epidermal growth factor receptor inhibitors (EGFRIs). METHODS:
      Normal human epidermal keratinocytes (NHEK) were incubated for 2 and 24h with
      different concentrations of EGFRI (erlotinib) for Western blot analysis and
      cytokine expression analysis, respectively. Inhibition of EGFR, extracellular
      signal-regulated kinase 1/2 (Erk 1/2) and c-Jun was examined by Western blot
      analysis. Cytokine concentrations were measured by enzyme-linked immunosorbent
      assay (ELISA) in the NHEK cell supernatant and also in the serum of 186 cancer
      patients who are followed up for EGFRI induced skin rash. RESULTS: A significant
      inhibitory effect of EGFRI was seen on EGFR (Y845), Erk 1/2 and c-Jun in a dose
      dependent manner. Further downstream, increased CC-chemokine ligand 2 (CCL2), CC
      chemokine ligand 5 (CCL5) and decreased interleukin-8 (IL-8) or CXCL8 expression
      was observed in keratinocytes. In EGFRI treated patients, low levels of serum
      CXCL8 corresponding to stronger EGFR inhibition were associated with a higher
      grade of skin toxicity (p=0.0016) and a prolonged overall survival (p=0.018).
      CONCLUSIONS: The results obtained in this study indicate that EGFRI can regulate
      cytokines by modulating EGFR signalling pathway in keratinocytes. Moreover, serum
      levels of CXCL8 in EGFRI treated patients may be important for individual EGFRI
      induced skin toxicity and patient's survival.

PMID- 24857782
TI  - May sediment contamination be xenoestrogenic to benthic fish? A case study with
      Solea senegalensis.
AB  - Within an environmental risk assessment framework of a moderately contaminated
      estuary (the Sado, SW Portugal), the present work intended to detect endocrine
      disruption in a flatfish, Solea senegalensis Kaup, 1858, and its potential
      relationship to organic toxicants. Animals were collected from two distinct areas
      in the estuary (industrial and rural) and from an external reference area.
      Hepatic vitellogenin (VTG) levels, cytochrome P450 (CYP1A) induction,
      ethoxyresorufin-O-deethylase (EROD) activity plus gonad histology were analysed.
      Males and females were sexually immature and showed no significant evidence of
      degenerative pathologies. However, hepatic VTG concentrations in males from the
      industrial area were higher than Reference, even reaching levels comparable to
      females, indicating low but measurable oestrogenic effects caused by the complex
      contaminant mixture in estuarine sediments. These individuals also presented
      elevated CYP1A induction and EROD activity, which is consistent with
      contamination by organic toxicants such as PAHs and other aryl hydrocarbon
      receptor (Ahr) -mediated toxicants. 

PMID- 24857783
TI  - Speciation of arsenic in saliva samples from a population of West Bengal, India.
AB  - Saliva, an easily accessible biofluid, is validated as biomarker of arsenic (As)
      exposure in several villages of West Bengal, India. Pentavalent arsenic [As(V)]
      was found to be the predominant species in saliva, with the amount of inorganic
      As [As(V) and trivalent form, As(III)] being more than half of the total As in
      the samples. Significant association was found between total daily ingestion of
      As and As(V) (r = 0.59; p = 0.000), As(III) (r = 0.60; p = 0.000),
      dimethylarsinous acid (DMA(V)) (r = 0.40; p = 0.000), and monomethylarsonous acid
      (MMA(V)) (r = 0.44; p = 0.000), implying that these species have mainly been
      derived from the methylation of the inorganic As in the water that study
      participants drank and the food they ate. Analysis of confounding effects of age,
      sex, smoking, body mass index and the prevalence of skin lesion suggests that
      women and controls with no skin lesion had a higher capacity to methylate the
      ingested As compared to the rest of the population. Thus, our study demonstrates
      that As species in saliva can be an useful tool to predict the individual
      susceptibility where higher As exposure and a lower methylation capacity are
      implicated in the development of As-induced health effects. 

PMID- 24857784
TI  - Biogeography of the marmosets and tamarins (Callitrichidae).
AB  - The marmosets and tamarins, Family Callitrichidae, are Neotropical primates with
      over 60 species and subspecies that inhabit much of South America. Although
      callitrichids exhibit a remarkable widespread distribution, attempts to unravel
      their biogeographic history have been limited by taxonomic confusion and the lack
      of an appropriate statistical biogeographic framework. Here, we construct a time
      calibrated multi-locus phylogeny from GenBank data and the callitrichid
      literature for 38 taxa. We use this framework to conduct statistical
      biogeographic analyses of callitrichids using BioGeoBEARS. The DIVAj model is the
      best supported reconstruction of biogeographic history among our analyses and
      suggests that the most recent common ancestor to the callitrichids was widespread
      across forested regions c. 14 Ma. There is also support for multiple
      colonizations of the Atlantic forest region from the Amazon basin, first by
      Leontopithecus c. 11 Ma and later by Callithrix c. 5 Ma. Our results show support
      for a 9 million year old split between a small-bodied group and large-bodied
      group of tamarins. These phylogenetic data, in concert with the consistent
      difference in body size between the two groups and geographical patterns (small
      bodied tamarins and large-bodied tamarins have an unusually high degree of
      geographic overlap for congeners) lend support to our suggestion to split
      Saguinus into two genera, and we propose the use of distinct generic names;
      Leontocebus and Saguinus, respectively.

PMID- 24857785
TI  - Comparison of targeted next-generation sequencing with conventional sequencing
      for predicting the responsiveness to epidermal growth factor receptor-tyrosine
      kinase inhibitor (EGFR-TKI) therapy in never-smokers with lung adenocarcinoma.
AB  - PURPOSE: To investigate the clinical utility of targeted next-generation
      sequencing (NGS) for predicting the responsiveness to epidermal growth factor
      receptor (EGFR)-tyrosine kinase inhibitor (TKI) therapy, we compared the efficacy
      with conventional sequencing in never-smokers with lung adenocarcinoma (NSLAs).
      PATIENTS AND METHODS: We obtained DNA from 48 NSLAs who received gefitinib or
      erlotinib for their recurrent disease after surgery. Sanger sequencing and
      peptide nucleic acid clamp polymerase chain reaction (PCR) were used to analyze
      EGFR, KRAS, BRAF, and PIK3CA mutations. We analyzed ALK, RET, and ROS1
      rearrangements by fluorescent in situ hybridization or reverse transcriptase-PCR
      and quantitative real-time PCR. After molecular screening, Ion Torrent NGS was
      performed in 31 cases harboring only EGFR exon 19 deletions (19DEL), an L858R
      mutation, or none of the above mutations. RESULTS: The 31 samples were divided
      into four groups: (1) responders to EGFR-TKIs with only 19DEL or L858R (n=15);
      (2) primary resistance to EGFR-TKI with only 19DEL or L858R (n=4); (3) primary
      resistance to EGFR-TKI without any mutations (n=8); (4) responders to EGFR-TKI
      without any mutations (n=4). With NGS, all conventionally detected mutations were
      confirmed except for one L858R in group 2. Additional uncovered predictive
      mutations with NGS included one PIK3CA E542K in group 2, two KRAS (G12V and
      G12D), one PIK3CA E542K, one concomitant PIK3CA and EGFR L858R in group 3, and
      one EGFR 19DEL in group 4. CONCLUSIONS: Targeted NGS provided a more accurate and
      clinically useful molecular classification of NSLAs. It may improve the efficacy
      of EGFR-TKI therapy in lung cancer.

PMID- 24857786
TI  - A luciferase-based method for assay of 5'-adenylylsulfate reductase.
AB  - A luciferase-based method was developed for measurement of 5'-adenylylsulfate
      (APS) reductase (APR), an enzyme of the reductive sulfate assimilation pathway in
      prokaryotes and plants. APR catalyzes the two-electron reduction of APS and forms
      sulfite and adenosine 5'-monophospahate (AMP). The luciferase-based assay
      measures AMP production using an enzyme-coupled system that generates
      luminescence. The method is shown to provide an accurate measurement of APR
      kinetic properties and can be used for both endpoint and continuous assays. APR
      activity can be measured from pure enzyme preparations as well as from crude
      protein extracts of tissues. In addition, the assay is ideally suited to high
      throughput sample analysis of APR activity in a microtiter dish format. The
      method adds new capability to the study of the biochemistry and physiology of
      APR. 

PMID- 24857788
TI  - In situ generation of self-enhanced luminophore by beta-lactamase catalysis for
      highly sensitive electrochemiluminescent aptasensor.
AB  - This work described a new electrogenerated chemiluminescence (ECL) aptasensor for
      ultrasensitive detection of thrombin (TB) based on the in situ generating self
      enhanced luminophore by beta-lactamase catalysis for signal amplification.
      Briefly, a ruthenium complex (Ru-Amp), including two regions of
      [Ru(phen)2(cpaphen)](2+) and ampicillin (Amp), was synthesized as a self-enhanced
      ECL luminophore, which can produce an ECL signal through intramolecular
      interactions. Then, carbon nanotubes (CNTs) were used for immobilization of Ru
      Amp via pi-pi stacking interactions to form the Ru-Amp@CNTs nanocomposite. Using
      poly(ethylenimine) (PEI) as a linkage reagent, Au nanocages (AuNCs), owing to
      their electronic property and large surface areas, were decorated to the CNTs to
      form the Ru-Amp@CNTs-PEI-AuNCs nanocomposites, which were further used to
      immobilize thrombin binding aptamer II (TBA II) to form a signal probe (Ru
      Amp@CNTs-PEI-AuNCs-TBA II). Through "sandwich" tactics, TBA II bioconjugates, TB
      and TBA I were immobilized onto the gold nanoparticles modified electrode. Then,
      with the enzyme catalysis of beta-lactamase, a novel self-enhanced ECL
      luminophore (Ru-AmpA) was in situ produced, which could exhibit a significant
      enhancement of ECL signal, due to the structure transformation of an amide bond
      into a secondary amine. A sandwich ECL assay for TB detection was developed with
      excellent sensitivity of a concentration variation from 1.0 fM to 1.0 pM and a
      detection limit of 0.33 fM. Therefore, the self-enhanced ECL luminophore,
      combining the further enhancement by in situ enzymatic reaction, is expected to
      have potential applications in biotechnology and clinical diagnosis. 

PMID- 24857787
TI  - A chromogenic assay of substrate depletion by thiol dioxygenases.
AB  - A fast and easy method for enzyme activity assays using the chromogenic Ellman
      reagent, 5,5'-dithiobis(2-nitrobenzoic acid), was developed. The method was used
      to measure the activity of the nonheme mono-iron enzyme cysteine dioxygenase.
      Quantifying the depletion of the substrate, cysteine, allowed standard kinetic
      parameters to be determined for the enzyme from Rattus norvegicus. The assay was
      also used to quickly test the effects of ionic strength, pH, enzyme storage
      conditions, and potential inhibitors and activators. This assay facilitates a
      higher throughput than available HPLC-based assays, as it enjoys the advantages
      of fewer sample handling steps, implementation in a 96-well format, and speed. In
      addition, the relative specificity of Ellman's reagent, coupled with its reaction
      with a wide range of thiols, means that this assay is applicable to many enzymes.
      Finally, the use of readily available reagents and instrumentation means that
      this assay can be used by practically any research group to compare results with
      those of other groups. 

PMID- 24857789
TI  - Evaluation of immunologic effect of Enniatin A and quantitative determination in
      feces, urine and serum on treated Wistar rats.
AB  - Study of dietary supplementation with ENN A mycotoxin during 28 days of exposure
      time on Wistar rats to determinate its levels in serum, urine and feces and, to
      evaluate the immunologic effect in peripheral blood lymphocytes (PBL) is
      presented. The first method for ENN A extraction, determination and detection by
      LC-MS/MS in serum, urine and feces samples is reported. ENN A food dose
      administrated was detected in serum samples and influenced lymphocyte
      phenotyping. Levels in serum were founded from the second week of the experiment;
      reaching values of 4.76 MUg/ml on the fourth week, which corresponds to 3.24
      MUg/ml in blood. PBL as T helper (CD4(+)) were presented in greater percentages
      compared to control (p <= 0.001), while T cytotoxic (CD8(+)) decreased
      significantly compared to control (p <= 0.001). ENN A treatment significantly
      increased CD4(+)/CD3(+) and CD4(+)/CD8(+) ratios but significantly decreased
      CD8(+)/CD3(+) ratio. CD4(+)/CD8(+) ratio was 2.94:1, indicating that PBL surface
      antigen expression and immune status in Wistar rats treated were impaired by the
      ENN A mycotoxin. 

PMID- 24857790
TI  - Discovery of a novel vascular endothelial growth factor (VEGF) with no affinity
      to heparin in Gloydius tsushimaensis venom.
AB  - Strong vascular permeability enhancing activity was found only in the venom of
      Gloydius tsushimaensis, in Tsushima island, Japan, when examined together with
      the venoms of G. blomhoffii snakes in several areas of Japan and of G.
      ussuriensis in South Korea. The active protein purified by using Superdex 75 and
      Mono Q columns showed no affinity to heparin, and migrated on SDS-PAGE with
      molecular weights of 26 and 13 kDa under nonreducing and reducing conditions,
      respectively, showing that it exists as homodimer. Its N-terminal amino acid
      sequence was highly homologous to those of snake venom vascular endothelial
      growth factors (VEGFs). The sequence of this protein, named GtVF, was inferred
      from the one base-substituted two cDNAs (438 bp) obtained via the 3' RACE. The
      phylogenetic analysis suggested the presence of a new type of snake venom VEGFs
      including GtVF with no affinity to heparin in addition to the known three types
      of snake venom VEGFs with high affinity to heparin. Since the vascular
      permeability enhancement by GtVF was inhibited by the antibody against kinase
      insert domain-containing receptor (KDR), the vascular permeability enhancing
      activity of GtVF arises through KDR but without heparin binding.

PMID- 24857791
TI  - Design and synthesis of enantiomeric (R)- and (S)-copper(II) and diorganotin(IV)
      based antitumor agents: their in vitro DNA binding profile, cleavage efficiency
      and cytotoxicity studies.
AB  - New chiral reduced Schiff base ligands (R)/(S)-2-(2-hydroxy-1
      phenylethylaminomethyl)phenol (L), (R)/(S)-2-(benzylamino)-2-phenylethanol (L')
      and their Cu(II)/organotin(IV) complexes (1-4) were synthesized and thoroughly
      characterized. Preliminary in vitro DNA binding studies of (R)- and (S)
      enantiomeric pairs of ligands L, L' and complexes 1-4 were carried out employing
      UV-vis, fluorescence and circular dichroic techniques to evaluate their
      enantioselective DNA binding potential, thereby to act as antitumor
      chemotherapeutic drug entities. The observations demonstrated that S-enantiomer
      of Cu(II) complex, 1 binds more avidly to DNA in comparison to its R-enantiomeric
      form and organotin(IV) complex 2. This was further established by Kb and Ksv
      values of ligands L and L' and (S)-/(R)-1-4 complexes, which demonstrated
      multifold increase in case of S-enantiomer of copper complex 1 in comparison to
      its R-enantiomeric form. This clearly demonstrates the chiral preference of S
      enantiomer over R-enantiomer and its potency to act as a chemotherapeutic agent.
      Cleavage studies of 1-4 with pBR322 plasmid DNA were carried out, noticeably, S
      enantiomer of complex 1 exhibited effective DNA cleavage efficiency in absence of
      external agents. The cytotoxicity of ligands L and L' and (S)-/(R)-1-4 complexes
      was examined on a panel of 19 human tumor cell lines of different histological
      origins by SRB assay. In the both the cases, the S-enantiomer of complex 1 and 3
      revealed remarkably good cytotoxic activity (GI50 values <10) against T24
      (Urinary Bladder), DU145 (Prostate), U373MG (Astrocytoma) and HCT15, SW620
      (Colon) clearly underlining the influence of enantiomeric discrimination.
      Interestingly, ligands L, L' and rest of the complexes demonstrated moderate
      cytotoxic activity (GI50 values <40). 

PMID- 24857792
TI  - Enzyme activated photodynamic therapy for methicillin-resistant Staphylococcus
      aureus infection both inv itro and in vivo.
AB  - In recent years, methicillin-resistant Staphylococcus aureus (MRSA) has become
      one of the most common multi-drug resistant bacteria in both hospital and
      community. The aim of this study is to investigate the selective inhibition of
      MRSA by a modified photosensitizer (LAEtNBS) in vitro and the efficacy of MRSA
      infection treatment by photodynamic therapy (PDT) with LAEtNBS in vivo. LAEtNBS
      was synthesized by adding a cationic photosensitizer molecule (EtNBS-COOH) and a
      quencher molecule to two side chains of cephalosporin, which was then shown to
      have similar absorption and emission wavelengths with EtNBS-COOH, but suppressed
      yields of fluorescence quantum and singlet oxygen. The selective inactivation and
      less phototoxicity of LAEtNBS, compared to that of EtNBS-COOH, were assessed and
      confirmed by conducting PDT to two Staphylococcus aureus strains and human skin
      cells at a fluence of 15 J/cm(2) with 640+/-10 nm LED light. Furthermore, using
      mouse skin wound model infected with 10(8) CFU of MRSA, we found that both
      LAEtNBS and EtNBS-COOH were able to treat MRSA infection and enhance wound
      repair. However, there was no significant difference in the two photosensitizers
      that might be due to the environment in vivo. Modification of the photosensitizer
      will be very beneficial for developing new strategies to treat drug resistant
      bacterial infection with less harm to host tissue.

PMID- 24857794
TI  - A mechanism-based classification of phantom limb pain.

PMID- 24857795
TI  - Adult social roles and alcohol use among American Indians.
AB  - American Indians are disproportionately burdened by alcohol-related problems.
      Yet, research exploring predictors of alcohol use among American Indians has been
      limited by cross-sectional designs and reservation-based samples. Guided by a
      life course developmental perspective, the current study used a subsample of
      American Indians (n=927) from the National Longitudinal Study of Adolescent
      Health (Add Health) to explore alcohol use (current drinking, usual number of
      drinks, and binge drinking) among this population. We examined whether adult
      social roles (i.e., cohabitation, marriage, parenthood, college enrollment, and
      full-time work) were linked to the rise and fall of alcohol use. Multi-level
      models demonstrated that adult social roles were linked to alcohol use at the
      within- and between-person levels. Becoming a parent was linked to a lower
      likelihood of being a current drinker, fewer alcoholic drinks, and less frequent
      binge drinking. Transitioning to full-time work was associated with a higher
      likelihood of being a current drinker and more frequent binge drinking. Results
      point to the importance of exploring within-group trajectories of alcohol use and
      highlight the protective and risky nature of adult social roles among American
      Indians. 

PMID- 24857797
TI  - [The degree of chronic renal failure is associated with the rate of pro
      inflammatory cytokines, hyperhomocysteinemia and with oxidative stress].
AB  - AIM: To evaluate pro-inflammatory cytokines, homocysteinemia and markers of
      oxidative status in the course of chronic renal failure. PATIENTS AND METHODS:
      One hundred and two patients (male/female: 38/64; age: 45+/-07 years) with
      chronic renal failure were divided into 4 groups according to the National Kidney
      Foundation classification. They included 28 primary stage renal failure patients,
      28 moderate stage renal failure, 28 severe stage renal failure and 18 end stage
      renal failure. The inflammatory status was evaluated by the determination of pro
      inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1beta,
      interleukin-6) and total homocysteine. Pro-oxidant status was assessed by
      assaying thiobarbituric acid reactive substances, hydroperoxides, and protein
      carbonyls. Antioxidant defence was performed by analysis of superoxide dismutase,
      catalase, glutathione peroxidase, glutathione reductase. RESULTS: Inflammatory
      markers were elevated in the end stage renal failure group compared to the other
      groups (P<0.001). Indeed, an increase in thiobarbituric acid reactive substances,
      hydroperoxides and protein carbonyls was noted in the end stage renal failure
      group in comparison with the other groups (P<0.001), while the levels of
      antioxidants enzymes activity were decreased in the study population (P<0.001).
      CONCLUSION: Impaired renal function is closely associated with the elevation of
      inflammatory markers leading to both increased markers of oxidative stress and
      decreased antioxidant defense.

PMID- 24857802
TI  - Emergence of NDM-1-producing Enterobacteriaceae in Porto Alegre, Brazil.
AB  - OBJECTIVES: To evaluate the emergence of New Delhi metallo-beta-lactamase 1 (NDM
      1)-producing Enterobacteriaceae isolates in Brazil. METHODS: From April to
      October 2013, following the detection of the first NDM-1-producing isolate, a
      surveillance study was performed for the detection of blaNDM-1 among
      Enterobacteriaceae isolates with reduced susceptibility to carbapenems in 17
      hospitals of Porto Alegre, Brazil. Real-time PCR was used to determine the
      presence of carbapenemase genes, which were further sequenced. Clonal relatedness
      was assessed by pulsed-field gel electrophoresis (PFGE). RESULTS: A total of 1134
      isolates were evaluated. blaNDM-1 was detected in 11 (0.97%) isolates: nine
      Enterobacter cloacae complex (eight belonging to a single clone recovered from
      two distinct hospitals and the other strain from a third hospital) and two
      Morganella morganii (belonging to a single clone recovered from one hospital).
      Most isolates presented high-level resistance to carbapenems. CONCLUSIONS: NDM-1
      producing Enterobacteriaceae have emerged rapidly in the hospitals of the
      Brazilian city where they were first detected. The emergence of NDM-1 in Brazil
      is of great concern, since it is a severe threat to antimicrobial therapy against
      Enterobacteriaceae in this country.

PMID- 24857803
TI  - New bioactive 2,6-diacetylpyridine bis(p-chlorophenylthiosemicarbazone) ligand
      and its Pd(II) and Pt(II) complexes: synthesis, characterization, cytotoxic
      activity and DNA binding ability.
AB  - Preparation and characterization of 2,6-diacetylpyridine bis((4)N-p
      chlorophenylthiosemicarbazone) ligand, H2L, and its palladium(II) and
      platinum(II) complexes [PdL] and [PtL], is described. The molecular structure of
      the two new complexes has been determined by single crystal X-ray diffraction.
      The ligand acts as dianionic tetradentate donor coordinating to the metal center
      in a square planar geometry through the pyridine nitrogen atom and the azomethine
      nitrogen and thione sulfur atoms from one thiosemicarbazone arm, the fourth
      coordination position is occupied by the hydrazine nitrogen atom of the other
      arm. New free ligand and its metal complexes have been evaluated for
      antiproliferative activity in vitro against NCI-H460, T-47D, A2780 and A2780cisR
      human cancer cell lines. The cytotoxicity data suggest that these compounds may
      be endowed with important antitumor properties, especially H2L and [PtL] since
      they are capable of not only circumvent cisplatin resistance in A2780cisR cells
      but also exhibit high antiproliferative activity in breast cancer T-47D cells.
      The interaction of H2L with calf thymus DNA was also investigated and its binding
      constant (Kb) determined. 

PMID- 24857804
TI  - Tyrosine nitration in peptides by peroxynitrite generated in situ in a light
      controlled platform: effects of pH and thiols.
AB  - Peroxynitrite has been shown to play a critical role in inflammation and affords
      3-nitrotyrosine as the hallmark product. The reported methods of generating this
      reactive nitrogen species in situ often fails to provide a high and steady flux
      of peroxynitrite resulting in poor yields of 3-nitrotyrosine. Herein we report a
      two-component peroxynitrite-generating platform in which this anion is produced
      in a biomimetic fashion and under the control of visible light. Incorporation of
      the nitric oxide- and superoxide-generating components in polymer matrices allows
      easy alterations of pH in the reaction wells of this platform. We have
      demonstrated very efficient nitration of tyrosine by peroxynitrite at different
      pH values and with varying concentrations of carbonate. In addition to tyrosine,
      a set of tyrosine-containing peptides was also studied. Presence of glutathione
      in the reaction wells increases the extent of tyrosine nitration in such peptide
      substrates presumably by raising the lifetime of nitric oxide in the reaction
      medium. When a cysteine residue was included in the sequence of the peptide, the
      extent of nitration of the tyrosine residue was found to depend on the position
      of the cysteine residue with respect to tyrosine. The extent of tyrosine
      nitration is strongly attenuated when the cysteine residue is directly adjacent
      to the tyrosine. This effect has been attributed to an intramolecular radical
      transfer mechanism. Taken together, results of this study demonstrate the
      potential of this light-controlled platform as a convenient bioanalytical tool in
      studying the reactions of peroxynitrite under widely varying conditions. 

PMID- 24857805
TI  - Spectroscopic studies on HasA from Yersinia pseudotuberculosis.
AB  - Heme acquisition system A (HasA) is known as a hemophore in Gram-negative
      pathogens. The ferric heme iron is coordinated by Tyr-75 and His-32 in holo-HasA
      from Pseudomonas aeruginosa (HasApa). In contrast, in holo-HasA from Yersinia
      pseudotuberculosis (HasAyp), our spectroscopic studies suggest that only Tyr-75
      coordinates to the ferric heme iron. The substitution of Gln-32 with alanine in
      HasAyp does not alter the spectroscopic properties, indicating that Gln-32 is not
      an axial ligand for the heme iron. Somewhat surprisingly, the Y75A mutant of
      HasAyp can capture a free hemin molecule but the rate of hemin uptake is slower
      than that of wild type, suggesting that the hydrophobic interaction in the heme
      pocket may also play a role in heme acquisition. Unlike in wild type apoprotein,
      ferric heme transfer from Hb to Y75A apo-HasAyp has not been observed. These
      results imply that coordination (bonding/interaction) between Tyr-75 and the heme
      iron is important for heme transfer from Hb. Interestingly, HasAyp differs from
      HasApa in its ability to bind the ferrous heme iron. Apo-HasAyp can capture
      ferrous heme and resonance Raman spectra of ferrous-carbon monoxide holo-HasAyp
      suggest that Tyr-75 is protonated when the heme iron is in the ferrous state. The
      ability of HasAyp to acquire the ferrous heme iron might be beneficial to Y.
      pseudotuberculosis, a facultative anaerobe in the Enterobacteriaceae family. 

PMID- 24857806
TI  - Sequential gastroenteritis episodes caused by 2 norovirus genotypes.
AB  - We investigated sequential episodes of acute norovirus gastroenteritis in a young
      child within an 11-month period. The infections were caused by 2 distinct
      genotypes (GII.4 and GII.6). Failure to achieve cross-protective immunity was
      linked to absence of an enduring and cross-reactive mucosal immune response, a
      critical consideration for vaccine design. 

PMID- 24857807
TI  - Transient epileptic amnesia mistaken for mild cognitive impairment? A high
      density EEG study.
AB  - Mild cognitive impairment (MCI) converts to Alzheimer's disease within a few
      years of diagnosis in up to 80% of patients. The identification among such a
      population of a rare form of epilepsy (transient epileptic amnesia [TEA]),
      characterized by mixed anterograde and retrograde amnesia with apparent
      preservation of other cognitive functions, excessively rapid decay of newly
      acquired memories, and loss of memories for salient personal events of the remote
      past, strongly affects prognosis and medical treatment. Our aim was to define the
      clinical utility of routine high-density electroencephalography (EEG) in patients
      with MCI for the detection of epilepsy, especially TEA. Using high-density EEG
      (256 channels), we were able to single out 3 cases of TEA previously misdiagnosed
      as MCI in this cohort of 76 consecutive patients with MCI diagnosed at our
      center. Antiepileptic treatment effectively stopped the acute episodes of memory
      loss. To our knowledge, this is the first report of an incidence of 4% of TEA
      recorded in such a cohort. 

PMID- 24857808
TI  - Outcome after anterior callosal section that spares the splenium in pediatric
      patients with drop attacks.
AB  - We report on the efficacy and safety of extended, one-stage anterior callosal
      section that spares the splenium, which is performed in a large series of
      pediatric patients with drop attacks. Twenty-nine pediatric patients with drop
      attacks were studied (19 males and 10 females; mean age: 9.9 years). As
      presurgical factors, the age at surgery, age at seizure onset, age at drop attack
      onset, sex, hemiparesis, severe mental retardation, electroencephalograph
      abnormalities, magnetic resonance imaging abnormalities, and
      (18)fluorodeoxyglucose positron emission tomography abnormalities were analyzed.
      All patients had multiple seizure types, including drop attacks, atypical absence
      seizures, complex partial seizures, tonic seizures, and generalized tonic-clonic
      seizures. All patients were developmentally impaired and had
      electroencephalograph results showing marked secondary bilateral synchrony. All
      patients received an extended, one-stage callosal section, leaving only the
      splenium intact. The mean follow-up time was 5.2 years. Seizure outcome
      (cessation of seizures or >= 90% seizure reduction) was achieved in 79.3% of
      patients with drop attacks. The families assessed the overall daily function as
      improved in 62.1% of the patients, unchanged in 24.1%, and worse in 13.8%. Family
      satisfaction with callosotomy was achieved in 82.8% of the patients. The majority
      of the patients had some degree of a transient acute postoperative disconnection
      syndrome that disappeared within 3 weeks. Postoperatively, patients showed a
      consistent increase in attention levels. We conclude that extended callosal
      sectioning that leaves the splenium intact should be considered a good palliative
      surgical option for pediatric patients with drop attacks and that diminishment of
      epileptic discharge synchrony is a good prognostic sign following callosotomy. We
      also found that the postoperative increase in attention levels was as useful as
      seizure control in improving the quality of life of these patients.

PMID- 24857809
TI  - Seizures and dementia in the elderly: Nationwide Inpatient Sample 1999-2008.
AB  - OBJECTIVES: This study aimed to examine the association between incidence of
      admission for a primary diagnosis of "seizure" or "epilepsy" and dementia in a
      nationally representative database, the Nationwide Inpatient Sample, among the
      elderly population (55 years of age and above) and to determine whether this
      relationship is different in individuals with Alzheimer's dementia versus those
      with non-Alzheimer's dementia. METHODS: Data were obtained from the Nationwide
      Inpatient Sample using appropriate ICD-9 codes. Frequencies and descriptive
      analysis adjusting for influence of comorbidities and confounders were utilized.
      A multivariate logistic regression model adjusted for age, gender, and race was
      used to further explore the relationship. RESULTS: Those with AD had a higher
      risk of developing seizures or epilepsy (OR=3.07, 95% CI=2.98-3.16) as compared
      with cases with NAD (OR=2.20, 95% CI=2.14-2.27). After adjusting for age, the
      association increased for patients with AD (OR=4.065, 95% CI=3.95-4.17) but not
      appreciably for patients with NAD (OR=2.68, 95% CI=2.60-2.75). Adding gender and
      race to the model did not change the relationship for either AD or NAD. Further
      adjustment for African-American race did not further change the relationship for
      AD and seizure (OR=3.96, 95% CI=3.854-4.077) as well as for NAD and seizure
      (OR=2.652, 95% CI=2.575-2.731). Similarly, Hispanic race did not change the
      relationship significantly for AD (OR=4.1, 95% CI=4.01-4.25) and NAD (OR=2.65,
      95% CI=2.56-2.74). CONCLUSION: Patients with AD have a higher prevalence of a
      seizure compared with patients with NAD. Younger patients with AD were more
      likely to have seizures. Race, when analyzed as a whole and separately as African
      American and Hispanic race, did not alter this relationship.

PMID- 24857810
TI  - Visual memory after epilepsy surgery in children: a standardized regression-based
      analysis of group and individual outcomes.
AB  - Visual memory is vulnerable to epilepsy surgery in adults, but studies in
      children suggest no change or small improvements. We investigated visual memory
      after epilepsy surgery, both group-wise and in individual children, using two
      techniques to assess change: 1) repeated measures analysis of variance (ANOVA)
      and 2) an empirically based technique for detecting cognitive change
      [standardized regression-based (SRB) analysis]. A prospective cohort consisting
      of 21 children completed comprehensive assessments of memory both before surgery
      (T0) and 6 (T1), 12 (T2), and 24 months (T3) after surgery. For each patient, two
      age- and gender-matched controls were assessed with the same tests at the same
      intervals. Repeated measures ANOVA replicated the results of previous studies
      reporting no change or minor improvements after surgery. However, group analysis
      of SRB results eliminated virtually all improvements, indicating that the ANOVA
      results were confounded by practice effects. Standardized regression-based group
      results showed that in fact patients scored lower after surgery than would be
      predicted based on their presurgical performance. Analysis of individual SRB
      results showed that per visual memory measure, an average of 18% of patients
      obtained a significantly negative SRB score, whereas, on average, only 2%
      obtained a significantly positive SRB score. At T3, the number of significantly
      negative SRB scores outweighed the number of significantly positive SRB scores in
      62% of patients. There were no clear associations of clinical variables
      (including side and site of surgery and postsurgical seizure freedom) with memory
      outcome. The present analysis revealed that given their individual presurgical
      functioning, many children obtained disappointing results on some visual memory
      tests after epilepsy surgery. Comparison of the SRB analysis with ANOVA results
      emphasizes the importance of empirically based techniques for detecting cognitive
      effects of epilepsy surgery in childhood.

PMID- 24857811
TI  - Lovastatin decreases the synthesis of inflammatory mediators during
      epileptogenesis in the hippocampus of rats submitted to pilocarpine-induced
      epilepsy.
AB  - Statins may act on inflammatory responses, decreasing oxidative stress and also
      reducing brain inflammation in several brain disorders. Epileptogenesis is a
      process in which a healthy brain becomes abnormal and predisposed to generating
      spontaneous seizures. We previously reported that lovastatin could prevent
      neuroinflammation in pilocarpine-induced status epilepticus (SE). In this
      context, this study investigated the long-lasting effects of lovastatin on mRNA
      expression of proinflammatory cytokines (interleukin-1beta, tumor necrosis factor
      alpha, interleukin-6) and the antiinflammatory cytokine IL-10 in the hippocampus
      during epileptogenesis by immunohistochemistry and real time polymerase chain
      reaction (RT-PCR) during the latent and chronic phases in the epilepsy model
      induced by pilocarpine in rats. For these purposes, four groups of rats were
      employed: saline (CONTROL), lovastatin (LOVA), pilocarpine (PILO), and
      pilocarpine plus lovastatin (PILO+LOVA). After pilocarpine injection (350mg/kg,
      i.p.), the rats were treated with 20mg/kg of lovastatin via an esophagic probe 2h
      after SE onset. All surviving rats were continuously treated during 15days,
      twice/day. The pilocarpine plus lovastatin group showed a significant decrease in
      the levels of IL-1beta, TNF-alpha, and IL-6 during the latent phase and a
      decreased expression of IL-1beta and TNF-alpha in the chronic phase when compared
      with the PILO group. Moreover, lovastatin treatment also induced an increased
      expression of the antiinflammatory cytokine, IL-10, in the PILO+LOVA group when
      compared with the PILO group in the chronic phase. Thus, our data suggest that
      lovastin may reduce excitotoxicity during epileptogenesis induced by pilocarpine
      by increasing the synthesis of IL-10 and decreasing proinflammatory cytokines in
      the hippocampus.

PMID- 24857812
TI  - Biomarkers and personalized therapy in chronic kidney diseases.
AB  - Numerous clinical trials are currently evaluating new strategies to halt the
      progression of renal damage in patients with chronic kidney diseases (CKDs).
      Unfortunately, none of them have considered that the lack of response to new
      therapies may be due to the pharmacogenetics/pharmacogenomics profile of the
      patient. The recent impact of high-throughput technologies used in genomics,
      proteomics and metabolomics may open a new way for discovering biomarkers that
      can provide us information about the mechanisms on the progression of renal
      damage. However, they can also be used for diagnosis and for selecting drugs,
      leading to personalized tailored therapy. The uses of classifiers formed by a
      list of genes, proteins and metabolites have been introduced into oncology and
      organ transplantation. These new approaches have recently also been used in the
      care of human glomerulonephritis. Integrating the large omic data sets with drug
      and disease databases could give the prediction of drug efficacy and side effects
      in CKDs. 

PMID- 24857813
TI  - Impact of structural and metabolic variations on the toxicity and carcinogenicity
      of hydroxy- and alkoxy-substituted allyl- and propenylbenzenes.
AB  - The metabolic fate of a compound is determined by numerous factors including its
      chemical structure. Although the metabolic options for a variety of functional
      groups are well understood and can often provide a rationale for the comparison
      of toxicity based on structural analogy, at times quite minor structural
      variations may have major consequences for metabolic outcomes and toxicity. In
      this perspective, the effects of structural variations on metabolic outcomes is
      detailed for a group of related hydroxy- and alkoxy-substituted allyl- and
      propenylbenzenes. These classes of compounds are naturally occurring constituents
      of a variety of botanical-based food items. The classes vary from one another by
      the presence or absence of alkylation of their para-hydroxyl substituents and/or
      the position of the double bond in the alkyl side chain. We provide an overview
      of how these subtle structural variations alter the metabolism of these important
      food-borne compounds, ultimately influencing their toxicity, particularly their
      DNA reactivity and carcinogenic potential. The data reveal that detailed
      knowledge of the consequences of subtle structural variations for metabolism is
      essential for adequate comparison of structurally related chemicals. Taken
      together, it is concluded that predictions in toxicological risk assessment
      should not be performed on the basis of structural analogy only but should
      include an analogy of metabolic pathways across compounds and species. 

PMID- 24857814
TI  - Cigarette smoking and gestational diabetes mellitus in Hispanic woman.
AB  - AIMS: Hispanic women are at increased risk of gestational diabetes mellitus (GDM)
      as compared to non-Hispanic white women. While smoking has been associated with
      increased risk of type 2 diabetes, studies of smoking and GDM are sparse and
      conflicting. Therefore, we evaluated the relationship between cigarette smoking
      and GDM in Hispanic women. METHODS: We conducted a pooled analysis of two
      Hispanic datasets based in Massachusetts: the UMass Medical Health Care dataset
      and the Proyecto Buena Salud dataset. A total of 3029 Hispanic prenatal care
      patients with singleton gestations were included. Cigarette smoking prior to and
      during pregnancy was collected via self-report. Diagnosis of GDM was abstracted
      from medical records and confirmed by study obstetricians. RESULTS: One-fifth of
      participants (20.4%) reported smoking prior to pregnancy, and 11.0% reported
      smoking in pregnancy. A total of 143 women (4.7%) were diagnosed with GDM. We did
      not observe an association between pre-pregnancy cigarette smoking and odds of
      GDM (multivariable OR=0.77, 95% CI 0.47, 1.25). In contrast, smoking during
      pregnancy was associated with a 54% reduction in odds of GDM (OR=0.46, 95% CI
      0.22, 0.95). However, this association was no longer statistically significant
      after adjustment for age, parity, and study site (OR=0.47, 95% CI 0.23, 1.00).
      CONCLUSIONS: In this population of Hispanic pregnant women, we did not observe
      statistically significant associations between pre-pregnancy smoking and odds of
      GDM. A reduction in odds of GDM among those who smoked during pregnancy was no
      longer apparent after adjustment for important diabetes risk factors.

PMID- 24857815
TI  - Thermoplastic polyurethane:polythiophene nanomembranes for biomedical and
      biotechnological applications.
AB  - Nanomembranes have been prepared by spin-coating mixtures of a polythiophene
      (P3TMA) derivative and thermoplastic polyurethane (TPU) using 20:80, 40:60, and
      60:40 TPU:P3TMA weight ratios. After structural, topographical, electrochemical,
      and thermal characterization, properties typically related with biomedical
      applications have been investigated: swelling, resistance to both hydrolytic and
      enzymatic degradation, biocompatibility, and adsorption of type I collagen, which
      is an extra cellular matrix protein that binds fibronectin favoring cell adhesion
      processes. The swelling ability and the hydrolytic and enzymatic degradability of
      TPU:P3TMA membranes increases with the concentration of P3TMA. Moreover, the
      degradation of the blends is considerably promoted by the presence of enzymes in
      the hydrolytic medium, TPU:P3TMA blends behaving as biodegradable materials. On
      the other hand, TPU:P3TMA nanomembranes behave as bioactive platforms stimulating
      cell adhesion and, especially, cell viability. Type I collagen adsorption largely
      depends on the substrate employed to support the nanomembrane, whereas it is
      practically independent of the chemical nature of the polymeric material used to
      fabricate the nanomembrane. However, detailed microscopy study of the morphology
      and topography of adsorbed collagen evidence the formation of different
      organizations, which range from fibrils to pseudoregular honeycomb networks
      depending on the composition of the nanomembrane that is in contact with the
      protein. Scaffolds made of electroactive TPU:P3TMA nanomembranes are potential
      candidates for tissue engineering biomedical applications. 

PMID- 24857816
TI  - Response to letter to the editor.

PMID- 24857817
TI  - Sodium selenite and vitamin E in preventing mercuric chloride induced renal
      toxicity in rats.
AB  - This study aims to investigate improving effects of sodium selenite and/or
      vitamin E on mercuric chloride-induced kidney impairments in rats. Wistar male
      rats were exposed either to sodium selenite (0.25mg/kgday), vitamin E
      (100mg/kgday), sodium selenite+vitamin E, mercuric chloride (1mg/kgday), sodium
      selenite+mercuric chloride, vitamin E+mercuric chloride and sodium
      selenite+vitamin E+mercuric chloride for 4weeks. Mercuric chloride exposure
      resulted in an increase in the uric acid, creatinine, blood urea nitrogen and
      malondialdehyde (MDA) levels and a decrease in the superoxide dismutase (SOD),
      catalase (CAT) and glutathione peroxidase (GPx) activities. Histopathological
      changes were detected in kidney tissues in mercuric chloride-treated groups. A
      significant decrease in the uric acid, creatinine, blood urea nitrogen and MDA
      levels and a significant increase in the SOD, CAT and GPx activities were
      observed in the supplementation of sodium selenite and/or vitamin E to mercuric
      chloride-treated groups. Conclusively, sodium selenite, vitamin E and vitamin
      E+sodium selenite significantly reduce mercuric chloride induced nephrotoxicity
      in rats, but not protect completely. 

PMID- 24857818
TI  - Letter to the editor: recent article by Anderson et al.(2013).

PMID- 24857819
TI  - Protective effect of resveratrol on sodium fluoride-induced oxidative stress,
      hepatotoxicity and neurotoxicity in rats.
AB  - Protective effect of resveratrol on sodium fluoride-induced oxidative stress,
      hepatotoxicity and neurotoxicity were studied in rats. A total of 28 Wistar
      albino male rats were used. Four study groups were randomly formed with seven
      animals in each. The groups were treated for 21days with distilled water (control
      group), with water containing 100ppm fluoride (fluoride group), with resveratrol
      (12.5mg/kg i.p., resveratrol group), or with 100ppm fluoride+12.5mg/kg
      resveratrol i.p. (fluoride+resveratrol group). At the end of the trial, blood
      samples were collected by cardiac puncture and tissue samples were taken
      simultaneously. The total antioxidant and oxidant status in plasma and tissues as
      well as plasma 8-hydroxydeoxyguanosine levels were measured. Histopathological
      analyses of rat liver and brain tissues were performed in all groups to identify
      any changes. In the fluoride group, the total oxidant levels increased in plasma,
      liver and brain and total antioxidant levels decreased, as did the plasma 8
      hydroxy-deoxyguanosine levels. These changes were prevented by co-administration
      of resveratrol. In addition, fluoride-associated severe histopathological changes
      in brain and liver tissues were not observed in the fluoride+resveratrol group.
      Consequently, these data suggested that resveratrol had beneficial effects in
      alleviating fluoride-induced oxidative stress. 

PMID- 24857820
TI  - FAM3A promotes vascular smooth muscle cell proliferation and migration and
      exacerbates neointima formation in rat artery after balloon injury.
AB  - The biological function of FAM3A, the first member of family with sequence
      similarity 3 (FAM3) gene family, remains largely unknown. This study aimed to
      determine its role in the proliferation and migration of vascular smooth muscle
      cells (VSMCs). Immunohistochemical staining revealed that FAM3A protein is
      expressed in the tunica media of rodent arteries, and its expression is reduced
      with an increase in prostaglandin E receptor 2 (EP2) expression after injury. In
      vitro, FAM3A overexpression promotes proliferation and migration of VSMCs,
      whereas FAM3A silencing inhibits these processes. In vivo, FAM3A overexpression
      results in exaggerated neointima formation of rat carotid artery after balloon
      injury. FAM3A activates Akt in a PI3K-dependent manner. In contrast, FAM3A
      induces ERK1/2 activation independent of PI3K. FAM3A protein is subcellularly
      located in mitochondria, where it affects ATP production and release. Activation
      of EP2 represses FAM3A expression, leading to impaired ATP production and release
      in VSMCs. FAM3A-induced activation of Akt and ERK1/2 pathways, proliferation and
      migration of VSMCs are inhibited by P2 receptor antagonist suramin. Furthermore,
      inhibition or knockdown of P2Y1 receptor inihibits FAM3A-induced proliferation
      and migration of VSMCs. In conclusion, FAM3A promotes proliferation and migration
      of VSMCs via P2Y1 receptor-mediated activation of Akt and ERK1/2 pathways. In
      injured vessels, FAM3A was repressed by upregulated EP2 expression, leading to
      the attenuation of ATP-P2Y1 receptor signaling, which is beneficial for
      preventing excessive proliferation and migration of VSMCs. 

PMID- 24857821
TI  - Treatment of binge eating disorder in racially and ethnically diverse obese
      patients in primary care: randomized placebo-controlled clinical trial of self
      help and medication.
AB  - The objective was to determine whether treatments with demonstrated efficacy for
      binge eating disorder (BED) in specialist treatment centers can be delivered
      effectively in primary care settings to racially/ethnically diverse obese
      patients with BED. This study compared the effectiveness of self-help cognitive
      behavioral therapy (shCBT) and an anti-obesity medication (sibutramine), alone
      and in combination, and it is only the second placebo-controlled trial of any
      medication for BED to evaluate longer-term effects after treatment
      discontinuation. 104 obese patients with BED (73% female, 55% non-white) were
      randomly assigned to one of four 16-week treatments (balanced 2-by-2 factorial
      design): sibutramine (N = 26), placebo (N = 27), shCBT + sibutramine (N = 26), or
      shCBT + placebo (N = 25). Medications were administered in double-blind fashion.
      Independent assessments were performed monthly throughout treatment, post
      treatment, and at 6- and 12-month follow-ups (16 months after randomization).
      Mixed-models analyses revealed significant time and medication-by-time
      interaction effects for percent weight loss, with sibutramine but not placebo
      associated with significant change over time. Percent weight loss differed
      significantly between sibutramine and placebo by the third month of treatment and
      at post-treatment. After the medication was discontinued at post-treatment,
      weight re-gain occurred in sibutramine groups and percent weight loss no longer
      differed among the four treatments at 6- and 12-month follow-ups. For binge
      eating, mixed-models revealed significant time and shCBT-by-time interaction
      effects: shCBT had significantly lower binge-eating frequency at 6-month follow
      up but the treatments did not differ significantly at any other time point.
      Demographic factors did not significantly predict or moderate clinical outcomes.
      Our findings suggest that pure self-help CBT and sibutramine did not show long
      term effectiveness relative to placebo for treating BED in racially/ethnically
      diverse obese patients in primary care. Overall, the treatments differed little
      with respect to binge-eating and associated outcomes. Sibutramine was associated
      with significantly greater acute weight loss than placebo and the observed weight
      regain following discontinuation of medication suggests that anti-obesity
      medications need to be continued for weight loss maintenance. Demographic factors
      did not predict/moderate clinical outcomes in this diverse patient group. 

PMID- 24857823
TI  - The impact of coronal alignment on distal radioulnar joint stability following
      distal radius fracture.
AB  - PURPOSE: Shift of the distal fragment of a distal radius fracture (DRF) in the
      coronal plane (coronal shift) may compromise the contributions of the distal
      oblique bundle (DOB) of the interosseous membrane to distal radioulnar joint
      (DRUJ) stability. The purpose of the study was to test our hypothesis that
      coronal shift of the distal fragment would increase dorsal-volar DRUJ
      displacement in response to applied load. METHODS: A distal radius osteotomy was
      performed proximal to the sigmoid notch base and the ulnar styloid was cut (to
      simulate triangular fibrocartilage complex detachment) in 10 cadaveric specimens.
      A volarly placed plate was used to shift the distal radius fragment radially in 2
      mm increments. A mechanical testing apparatus applied a 20 N load to the distal
      fragment perpendicular to the volar cortex with the forearm in neutral, 60
      degrees  pronation, and 60 degrees  supination. Dorsal-volar displacement of the
      radius relative to the fixed ulna was measured in the control state (DRF and
      ulnar styloid anatomically fixed) and in 3 positions (anatomical reduction, 2-mm
      coronal shift, 4-mm coronal shift) with ulnar styloid displacement. The specimens
      were dissected post hoc to evaluate for a distinct DOB (thickness, > 0.5 mm).
      Dorsal-volar DRUJ displacement was compared among testing and control states
      using analysis of variance. RESULTS: In specimens with a distinct DOB, 2-mm
      coronal shift significantly increased dorsal-volar DRUJ displacement. However,
      there was no difference in DRUJ displacement between 4-mm coronal shift and
      control state. Coronal shift did not affect dorsal-volar DRUJ displacement in
      specimens without a distinct DOB. CONCLUSIONS: In the setting of an ulnar styloid
      fracture, a 2-mm (but not a 4-mm) coronal shift of the DRF is associated with
      increased dorsal-volar DRUJ displacement in specimens with a distinct DOB, but
      not in specimens without a distinct DOB. CLINICAL RELEVANCE: Awareness of the
      importance of coronal shift may aid in prevention of DRUJ instability associated
      with DRF, especially in patients with a DOB.

PMID- 24857824
TI  - Mechanisms of reduced flavin transfer in the two-component flavin-dependent
      monooxygenases.
AB  - Two-component flavin-dependent enzymes are abundant in nature and are involved in
      a wide variety of biological reactions. These enzymes consist of a reductase
      which generates a reduced flavin and a monooxygenase that utilizes the reduced
      flavin as a substrate for monooxygenation. As reduced flavin is unstable and can
      be oxidized by oxygen, these enzymes must have a means to efficiently coordinate
      the transfer of the reduced flavin such that auto-oxidation can be minimized.
      Various types of experiments and methodologies have been used to probe the mode
      of reduced flavin transfer. Results from many systems have indicated that the
      transfer can be achieved by free diffusion and that the presence of one component
      has no influence on the kinetics of the other component. Contradicting results
      indicating that the transfer of the reduced flavin may be achieved via protein
      protein mediation also exist. Regardless of the mode of reduced flavin transfer,
      these enzymes have a means to control their overall kinetics such that the
      reaction rate is slow when the demand for oxygenation is not high. 

PMID- 24857825
TI  - Kinetic investigation of the rate-limiting step of manganese- and iron
      lipoxygenases.
AB  - Lipoxygenases (LOX) oxidize polyunsaturated fatty acids to hydroperoxides, which
      are generated by proton coupled electron transfer to the metal center with
      FeIIIOH- or MnIIIOH-. Hydrogen abstraction by FeIIIOH- of soybean LOX-1 (sLOX-1)
      is associated with a large deuterium kinetic isotope effect (D-KIE). Our goal was
      to compare the D-KIE and other kinetic parameters at different temperatures of
      sLOX-1 with 13R-LOX with catalytic manganese (13R-MnLOX). The reaction rate and
      the D-KIE of sLOX-1 with unlabeled and [11-2H2]18:2n-6 were almost temperature
      independent with an apparent D-KIE of ~56 at 30 degrees C, which is in agreement
      with previous studies. In contrast, the reaction rate of 13R-MnLOX increased 7
      fold with temperature (8-50 degrees C), and the apparent D-KIE decreased linearly
      from ~38 at 8 degrees C to ~20 at 50 degrees C. The kinetic lag phase of 13R
      MnLOX was consistently extended at low temperatures. The Phe337Ile mutant of 13R
      MnLOX, which catalyzes antarafacial hydrogen abstraction and oxygenation in
      analogy with sLOX-1, retained the large D-KIE and its temperature-dependent
      reaction rate. The kinetic differences between 13R-MnLOX and sLOX-1 may be due to
      protein dynamics, hydrogen donor-acceptor distances, and to the metal ligands,
      which may not equalize the 0.7V-gap between the redox potentials of the free
      metals.

PMID- 24857826
TI  - Investigating intrinsic connectivity networks using simultaneous BOLD and CBF
      measurements.
AB  - When the sensory cortex is stimulated and directly receiving afferent input,
      modulations can also be observed in the activity of other brain regions
      comprising spatially distributed, yet intrinsically connected networks,
      suggesting that these networks support brain function during task performance.
      Such networks can exhibit subtle or unpredictable task responses which can pass
      undetected by conventional general linear modelling (GLM). Additionally, the
      metabolic demand of these networks in response to stimulation remains
      incompletely understood. Here, we recorded concurrent BOLD and CBF measurements
      during median nerve stimulation (MNS) and compared GLM analysis with independent
      component analysis (ICA) for identifying the spatial, temporal and metabolic
      properties of responses in the primary sensorimotor cortex (S1/M1), and in the
      default mode (DMN) and fronto-parietal (FPN) networks. Excellent spatial and
      temporal agreement was observed between the positive BOLD and CBF responses to
      MNS detected by GLM and ICA in contralateral S1/M1. Values of the change in
      cerebral metabolic rate of oxygen consumption (Delta%CMRO2) and the
      Delta%CMRO2/Delta%CBF coupling ratio were highly comparable when using either GLM
      analysis or ICA to extract the contralateral S1/M1 responses, validating the use
      of ICA for estimating changes in CMRO2. ICA identified DMN and FPN network
      activity that was not detected by GLM analysis. Using ICA, spatially coincident
      increases/decreases in both BOLD and CBF signals to MNS were found in the FPN/DMN
      respectively. Calculation of CMRO2 changes in these networks during MNS showed
      that the Delta%CMRO2/Delta%CBF ratio is comparable between the FPN and S1/M1 but
      is larger in the DMN than in the FPN, assuming an equal value of the parameter M
      in the DMN, FPN and S1/M1. This work suggests that metabolism-flow coupling may
      differ between these two fundamental brain networks, which could originate from
      differences between task-positive and task-negative fMRI responses, but might
      also be due to intrinsic differences between the two networks. 

PMID- 24857827
TI  - Effects of selective serotonin reuptake inhibition on neural activity related to
      risky decisions and monetary rewards in healthy males.
AB  - Selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine are commonly
      prescribed antidepressant drugs targeting the dysfunctional serotonin (5-HT)
      system, yet little is known about the functional effects of prolonged serotonin
      reuptake inhibition in healthy individuals. Here we used functional MRI (fMRI) to
      investigate how a three-week fluoxetine intervention influences neural activity
      related to risk taking and reward processing. Employing a double-blinded parallel
      group design, 29 healthy young males were randomly assigned to receive 3 weeks of
      a daily dose of 40 mg fluoxetine or placebo. Participants underwent task-related
      fMRI prior to and after the three-week intervention while performing a card
      gambling task. The task required participants to choose between two decks of
      cards. Choices were associated with different risk levels and potential reward
      magnitudes. Relative to placebo, the SSRI intervention did not alter individual
      risk-choice preferences, but modified neural activity during decision-making and
      reward processing: During the choice phase, SSRI reduced the neural response to
      increasing risk in lateral orbitofrontal cortex, a key structure for value-based
      decision-making. During the outcome phase, a midbrain region showed an
      independent decrease in the responsiveness to rewarding outcomes. This midbrain
      cluster included the raphe nuclei from which serotonergic modulatory projections
      originate to both cortical and subcortical regions. The findings corroborate the
      involvement of the normally functioning 5HT-system in decision-making under risk
      and processing of monetary rewards. The data suggest that prolonged SSRI
      treatment might reduce emotional engagement by reducing the impact of risk during
      decision-making or the impact of reward during outcome evaluation.

PMID- 24857828
TI  - Prenatal alcohol exposure causes the over-expression of DHAND and EHAND by
      increasing histone H3K14 acetylation in C57 BL/6 mice.
AB  - Prenatal alcohol exposure leads to congenital heart abnormal development, its
      mechanisms are still unknown. Recent reports have associated alcohol exposure
      with histone H3 acetylation. In the present study, we have performed the
      experiments to test the hypothesis that histone H3K14 acetylation is the key role
      in the fetal heart leads to over-expression of cardiac specific genes DHAND and
      EHAND caused by prenatal alcohol exposure. Seventy pregnant C57BL/6 mice were
      divided randomly into seven groups (n=10). They were the untreated group,
      dimethyl sulfoxide group, alcohol exposure group, curcumin treatment group, both
      alcohol and curcumin treatment group, SAHA treatment group, both alcohol and SAHA
      treatment group. Fetal mouse hearts were collected on embryonic day 14.5. The
      changes of HATs activities, the acetylation levels of histone H3K14 (H3K14ac),
      the expression levels of cardiac specific genes DHAND and EHAND, and structure of
      chromatin were determined. Our data indicates that curcumin and SAHA
      significantly reduces and increases the activities of HATs and the levels of
      histone H3K14ac in fetal hearts, respectively. The expression of DHAND and EHAND
      is significantly down-regulated and up-regulated in the groups treated with
      curcumin and SAHA. Furthermore, our results from ChIP assays have shown that the
      histone H3K14ac connects with the DHAND and EHAND genes are significantly
      inhibited by curcumin and simulated by SAHA. Our study suggests that prenatal
      alcohol exposure causes the over-expression of DHAND and EHAND by increasing
      H3K14ac in mice. 

PMID- 24857829
TI  - Psychiatric outcomes amongst adult survivors of childhood burns.
AB  - BACKGROUND: Research on the adult psychiatric outcomes of childhood burns is
      limited. AIMS: To examine the rates of DSM-IV psychiatric disorder amongst adult
      survivors of paediatric burns, and to explore factors likely to contribute to
      variation in outcomes. In line with Meyer and colleagues [1], it was expected
      that high levels of psychopathology would be found. METHOD: Participants were 272
      adults hospitalised for burns during childhood between the years 1980 and 1990.
      Structured interviews and self-report questionnaires were used to assess
      psychiatric symptoms. RESULTS: Lifetime prevalence of any DSM-IV disorder was
      42%, 30% for depressive disorders, and 28% for anxiety disorders. Eleven percent
      had made a suicide attempt. Female gender, single relationship status, higher
      level of disfigurement, longer hospital stays and higher number of burn-related
      surgeries were associated with adverse psychiatric outcomes. CONCLUSIONS: High
      rates of suicidality and depression were concerning in adults with a history of
      childhood burns. Factors found to predict psychiatric outcomes could be used to
      direct interventions and further research is needed to establish how this could
      best be done.

PMID- 24857830
TI  - Intestinal dysbiosis: novel mechanisms by which gut microbes trigger and prevent
      disease.
AB  - New research has identified specific intestinal colonizing microbes that can have
      significant influence on health and disease. Evidence is reviewed supporting an
      association between Fusobacterium nucleatum and colon cancer and for a protective
      role of Faecalibacterium prausnitzii in inflammatory bowel disease, of
      Escherichia coli Nissle 1917 in acute intestinal inflammation, of Bifidobacterium
      infantis in neonatal necrotizing enterocolitis, and of Akkermansia muciniphila in
      obesity and diabetes. These novel bacteria are clinically relevant and present
      opportunities for more focused diagnosis of colon cancer and prevention of common
      diseases. 

PMID- 24857832
TI  - Data-driven estimation of cardiac electrical diffusivity from 12-lead ECG
      signals.
AB  - Diagnosis and treatment of dilated cardiomyopathy (DCM) is challenging due to a
      large variety of causes and disease stages. Computational models of cardiac
      electrophysiology (EP) can be used to improve the assessment and prognosis of
      DCM, plan therapies and predict their outcome, but require personalization. In
      this work, we present a data-driven approach to estimate the electrical
      diffusivity parameter of an EP model from standard 12-lead electrocardiograms
      (ECG). An efficient forward model based on a mono-domain, phenomenological
      Lattice-Boltzmann model of cardiac EP, and a boundary element-based mapping of
      potentials to the body surface is employed. The electrical diffusivity of
      myocardium, left ventricle and right ventricle endocardium is then estimated
      using polynomial regression which takes as input the QRS duration and electrical
      axis. After validating the forward model, we computed 9500 EP simulations on 19
      different DCM patients in just under three seconds each to learn the regression
      model. Using this database, we quantify the intrinsic uncertainty of electrical
      diffusion for given ECG features and show in a leave-one-patient-out cross
      validation that the regression method is able to predict myocardium diffusion
      within the uncertainty range. Finally, our approach is tested on the 19 cases
      using their clinical ECG. 84% of them could be personalized using our method,
      yielding mean prediction errors of 18.7ms for the QRS duration and 6.5 degrees 
      for the electrical axis, both values being within clinical acceptability. By
      providing an estimate of diffusion parameters from readily available clinical
      data, our data-driven approach could therefore constitute a first calibration
      step toward a more complete personalization of cardiac EP. 

PMID- 24857835
TI  - Adaptation of Lorke's method to determine and compare ED50 values: the cases of
      two anticonvulsants drugs.
AB  - INTRODUCTION: We determined the median effective dose (ED50) values for the
      anticonvulsants phenobarbital and sodium valproate using a modification of
      Lorke's method. This modification allowed appropriate statistical analysis and
      the use of a smaller number of mice per compound tested. METHODS: The
      anticonvulsant activities of phenobarbital and sodium valproate were evaluated in
      male CD1 mice by maximal electroshock (MES) and intraperitoneal administration of
      pentylenetetrazole (PTZ). The anticonvulsant ED50 values were obtained through
      modifications of Lorke's method that involved changes in the selection of the
      three first doses in the initial test and the fourth dose in the second test.
      Furthermore, a test was added to evaluate the ED50 calculated by the modified
      Lorke's method, allowing statistical analysis of the data and determination of
      the confidence limits for ED50. RESULTS: The ED50 for phenobarbital against MES-
      and PTZ-induced seizures was 16.3mg/kg and 12.7mg/kg, respectively. The sodium
      valproate values were 261.2mg/kg and 159.7mg/kg, respectively. DISCUSSION: These
      results are similar to those found using the traditional methods of finding ED50,
      suggesting that the modifications made to Lorke's method generate equal results
      using fewer mice while increasing confidence in the statistical analysis. This
      adaptation of Lorke's method can be used to determine median letal dose (LD50) or
      ED50 for compounds with other pharmacological activities.

PMID- 24857836
TI  - Non-invasive measure of respiratory mechanics and conventional respiratory
      parameters in conscious large animals by high frequency Airwave Oscillometry.
AB  - INTRODUCTION: A number of drugs in clinical trials are discontinued due to
      potentially life-threatening airway obstruction. As some drugs may not cause
      changes in core battery parameters such as tidal volume (Vt), respiratory rate
      (RR) or minute ventilation (MV), including measurements of respiratory mechanics
      in safety pharmacology studies represents an opportunity for design refinement.
      The present study aimed to test a novel non-invasive methodology to concomitantly
      measure respiratory system resistance (Rrs) and conventional respiratory
      parameters (Vt, RR, MV) in conscious Beagle dogs and cynomolgus monkeys. METHODS:
      An Airwave Oscillometry system (tremoFlo; THORASYS Inc., Montreal, Canada) was
      used to concomitantly assess Rrs and conventional respiratory parameters before
      and after intravenous treatment with a bronchoactive agent. Respiratory mechanics
      measurements were performed by applying a short (i.e. 16s) single high frequency
      (19Hz) waveform at the subject's airway opening via a face mask. During
      measurements, pressure and flow signals were recorded. After collection of
      baseline measurements, methacholine was administered intravenously to Beagle dogs
      (n=6) and cynomolgus monkeys (n=4) at 8 and 68MUg/kg, respectively. RESULTS: In
      dogs, methacholine induced significant increases in Vt, RR and MV while in
      monkeys, it only augmented RR. A significant increase in Rrs was observed after
      methacholine administration in both species with mean percentage peak increases
      from baseline of 88 (53)% for dogs and 28 (16)% for cynomolgus monkeys.
      CONCLUSION: Airwave Oscillometry appears to be a promising non-invasive
      methodology to enable respiratory mechanics measurements in conscious large
      animals, a valuable refinement in respiratory safety pharmacology.

PMID- 24857839
TI  - Metabolomics-based search for therapeutic agents for non-alcoholic
      steatohepatitis.
AB  - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the commonest form of
      chronic liver disease in developed countries. Non-alcoholic steatohepatitis
      (NASH), which represents advanced stage NAFLD, is increasingly being recognized
      as a major cause of liver-related morbidity and mortality. However, no effective
      drugs against NASH have yet been developed. Therefore, we searched for candidate
      therapeutic agents based on the changes in levels of hepatic metabolites via gas
      chromatography mass spectrometry (GC/MS)-based metabolome analysis of livers from
      methionine-choline deficient (MCD) diet-fed mice, a mouse model of NASH. METHODS:
      The metabolites were extracted from the livers of the MCD diet-fed mice and then
      analyzed using GC/MS. Subsequently, the MCD diet-fed mice were supplemented with
      hypotaurine, and the therapeutic effects of hypotaurine against steatohepatitis
      were evaluated. RESULTS: Ninety-nine metabolites were detected in the livers of
      the MCD diet-induced steatohepatitis model mice. Among these metabolites,
      hypotaurine exhibited the greatest decrease in its concentration in the mice.
      Supplementation with 2 mmol/kgBW hypotaurine attenuated liver injuries and fat
      accumulation caused by the MCD diet-induced steatohepatitis. Furthermore, 10
      mmol/kgBW hypotaurine supplementation ameliorated fibrosis and oxidative stress
      induced by the MCD diet. CONCLUSION: The present metabolome analysis-based study
      demonstrated that hypotaurine is a novel candidate therapeutic agent for NASH.

PMID- 24857840
TI  - Effects of the delta opioid agonist AZD2327 upon operant behaviors and assessment
      of its potential for abuse.
AB  - AZD2327 is a brain-penetrant agonist at delta opioid receptors which has
      antidepressant and anxiolytic properties in a wide array of animal models. As
      part of the preclinical safety pharmacology assessment, a number of studies were
      conducted in order to characterize its behavioral effects and its potential for
      abuse, in order to enable testing in humans. AZD2327 produced only modest effects
      when tested in a multiple fixed-ratio differential reinforcement of low rate
      schedule in rats, and did not enhance the rate-suppressing effects of ethanol in
      the procedure. In a suppressed responding test, AZD2327 only reduced rates of
      unpunished responding. In drug discrimination studies, AZD2327 produced partial
      or no generalization from known drugs of abuse. In primates trained to self
      administer cocaine, substitution with AZD2327 did not result in appreciable self
      administration of AZD2327, indicating that it does not behave as a positive
      reinforcer under the present conditions. Following termination of repeated
      administration of AZD2327, no signs of physical dependence (withdrawal) were
      noted. Overall, the data suggest that AZD2327 does not possess a high potential
      for abuse, and appears to have only subtle behavioral effects as measured by
      operant behaviors. 

PMID- 24857842
TI  - Sub-Saharan Africa fast-tracks towards family medicine.

PMID- 24857843
TI  - Family medicine training in sub-Saharan Africa: South-South cooperation in the
      Primafamed project as strategy for development.
AB  - BACKGROUND: Health-care systems based on primary health care (PHC) are more
      equitable and cost effective. Family medicine trains medical doctors in
      comprehensive PHC with knowledge and skills that are needed to increase quality
      of care. Family medicine is a relatively new specialty in sub-Saharan Africa.
      OBJECTIVE: To explore the extent to which the Primafamed South-South cooperative
      project contributed to the development of family medicine in sub-Saharan Africa.
      METHODS: The Primafamed (Primary Health Care and Family Medicine Education)
      project worked together with 10 partner universities in sub-Saharan Africa to
      develop family medicine training programmes over a period of 2.5 years. A SWOT
      (strengths, weaknesses, opportunities and threats) analysis was done and the
      training development from 2008 to 2010 in the different partner universities was
      analysed. RESULTS: During the 2.5 years of the Primafamed project, all partner
      universities made progress in the development of their family medicine training
      programmes. The SWOT analysis showed that at both national and international
      levels, the time is ripe to train medical doctors in family medicine and to
      integrate the specialty into health-care systems, although many barriers,
      including little awareness, lack of funding, low support from other specialists
      and reserved support from policymakers, are still present. CONCLUSIONS: Family
      medicine can play an important role in health-care systems in sub-Saharan Africa;
      however, developing a new discipline is challenging. Advocacy, local ownership,
      action research and support from governments are necessary to develop family
      medicine and increase its impact. The Primafamed project showed that development
      of sustainable family medicine training programmes is a feasible but slow
      process. The South-South cooperation between the ten partners and the South
      African departments of family medicine strengthened confidence at both national
      and international levels.

PMID- 24857844
TI  - Using in vivo biotinylated ubiquitin to describe a mitotic exit ubiquitome from
      human cells.
AB  - Mitotic division requires highly regulated morphological and biochemical changes
      to the cell. Upon commitment to exit mitosis, cells begin to remove mitotic
      regulators in a temporally and spatially controlled manner to bring about the
      changes that reestablish interphase. Ubiquitin-dependent pathways target these
      regulators to generate polyubiquitin-tagged substrates for degradation by the 26S
      proteasome. However, the lack of cell-based assays to investigate in vivo
      ubiquitination limits our knowledge of the identity of substrates of ubiquitin
      mediated regulation in mitosis. Here we report an in vivo ubiquitin tagging
      system used in human cells that allows efficient purification of ubiquitin
      conjugates from synchronized cell populations. Coupling purification with mass
      spectrometry, we have identified a series of mitotic regulators targeted for
      polyubiquitination in mitotic exit. We show that some are new substrates of the
      anaphase-promoting complex/cyclosome and validate KIFC1 and RacGAP1/Cyk4 as two
      such targets involved respectively in timely mitotic spindle disassembly and cell
      spreading. We conclude that in vivo biotin tagging of ubiquitin can provide
      valuable information about the role of ubiquitin-mediated regulation in processes
      required for rebuilding interphase cells. 

PMID- 24857845
TI  - Is aerosol-based transmission of Middle East respiratory syndrome coronavirus
      possible?

PMID- 24857846
TI  - Reply to Karagoz et al.

PMID- 24857847
TI  - Coral calcification under daily oxygen saturation and pH dynamics reveals the
      important role of oxygen.
AB  - Coral reefs are essential to many nations, and are currently in global decline.
      Although climate models predict decreases in seawater pH (~0.3 units) and oxygen
      saturation (~5 percentage points), these are exceeded by the current daily pH and
      oxygen fluctuations on many reefs (pH 7.8-8.7 and 27-241% O2 saturation). We
      investigated the effect of oxygen and pH fluctuations on coral calcification in
      the laboratory using the model species Acropora millepora. Light calcification
      rates were greatly enhanced (+178%) by increased seawater pH, but only at
      normoxia; hyperoxia completely negated this positive effect. Dark calcification
      rates were significantly inhibited (51-75%) at hypoxia, whereas pH had no effect.
      Our preliminary results suggest that within the current oxygen and pH range,
      oxygen has substantial control over coral growth, whereas the role of pH is
      limited. This has implications for reef formation in this era of rapid climate
      change, which is accompanied by a decrease in seawater oxygen saturation owing to
      higher water temperatures and coastal eutrophication. 

PMID- 24857848
TI  - Endothelin signalling in iridophore development and stripe pattern formation of
      zebrafish.
AB  - Colour patterns of adult fish are composed of several different types of pigment
      cells distributing in the skin during juvenile development. The zebrafish, Danio
      rerio, displays a striking pattern of dark stripes of melanophores interspersed
      with light stripes of xanthophores. A third cell type, silvery iridophores,
      contributes to both stripes and plays a crucial role in adult pigment pattern
      formation. Several mutants deficient in iridophore development display similar
      adult phenotypes with reduced numbers of melanophores and defects in stripe
      formation. This indicates a supporting role of iridophores for melanophore
      development and maintenance. One of these mutants, rose (rse), encodes the
      Endothelin receptor b1a. Here we describe a new mutant in zebrafish, karneol
      (kar), which has a phenotype similar to weak alleles of rse with a reduction in
      iridophore numbers and defects of adult pigment patterning. We show that, unlike
      rse, kar is not required in iridophores. The gene defective in the kar mutant
      codes for an endothelin-converting enzyme, Ece2, which activates endothelin
      ligands by proteolytic cleavage. By morpholino-mediated knockdown, we identify
      Endothelin 3b (Edn3b) as the ligand for endothelin receptor signalling in larval
      iridophores. Thus, Endothelin signalling is involved in iridophore development,
      proliferation and stripe morphogenesis in larvae as well as adult zebrafish. In
      mammals the pathway is required for melanocyte development; therefore, our
      results indicate a previously unrecognized close evolutionary relationship
      between iridophores in zebrafish and melanocytes in mammals. 

PMID- 24857849
TI  - Low dose tubulin-binding drugs rescue peroxisome trafficking deficit in patient
      derived stem cells in Hereditary Spastic Paraplegia.
AB  - Hereditary Spastic Paraplegia (HSP) is a genetically heterogeneous group of
      disorders, diagnosed by progressive gait disturbances with muscle weakness and
      spasticity, for which there are no treatments targeted at the underlying
      pathophysiology. Mutations in spastin are a common cause of HSP. Spastin is a
      microtubule-severing protein whose mutation in mouse causes defective axonal
      transport. In human patient-derived olfactory neurosphere-derived (ONS) cells,
      spastin mutations lead to lower levels of acetylated alpha-tubulin, a marker of
      stabilised microtubules, and to slower speed of peroxisome trafficking. Here we
      screened multiple concentrations of four tubulin-binding drugs for their ability
      to rescue levels of acetylated alpha-tubulin in patient-derived ONS cells. Drug
      doses that restored acetylated alpha-tubulin to levels in control-derived ONS
      cells were then selected for their ability to rescue peroxisome trafficking
      deficits. Automated microscopic screening identified very low doses of the four
      drugs (0.5 nM taxol, 0.5 nM vinblastine, 2 nM epothilone D, 10 uM noscapine) that
      rescued acetylated alpha-tubulin in patient-derived ONS cells. These same doses
      rescued peroxisome trafficking deficits, restoring peroxisome speeds to untreated
      control cell levels. These results demonstrate a novel approach for drug
      screening based on high throughput automated microscopy for acetylated alpha
      tubulin followed by functional validation of microtubule-based peroxisome
      transport. From a clinical perspective, all the drugs tested are used clinically,
      but at much higher doses. Importantly, epothilone D and noscapine can enter the
      central nervous system, making them potential candidates for future clinical
      trials. 

PMID- 24857851
TI  - Specific Mindfulness Skills Differentially Predict Creative Performance.
AB  - Past work has linked mindfulness to improved emotion regulation, interpersonal
      skills, and basic cognitive abilities, but is unclear about the relation between
      mindfulness and creativity. Studies examining effects of mindfulness on factors
      pertinent to creativity suggest a uniform and positive relation, whereas work on
      specific mindfulness skills suggests that mindfulness skills may differentially
      predict creativity. To test whether the relation between mindfulness and
      creativity is positive and uniform (the uniform hypothesis) or differentially
      depends on particular components of mindfulness (the differential hypothesis), we
      conducted four studies in which mindfulness skills were measured, extensively
      trained, or manipulated with a short, incidental meditation session. Results
      supported a differential relation between mindfulness and creativity: Only the
      ability to observe and attend to various stimuli consistently and positively
      predicted creativity. Results regarding other mindfulness skills were less
      consistent. Implications for theory and practice are discussed.

PMID- 24857852
TI  - Indirect application of near infrared light induces neuroprotection in a mouse
      model of parkinsonism - an abscopal neuroprotective effect.
AB  - We have previously shown near infrared light (NIr), directed transcranially,
      mitigates the loss of dopaminergic cells in MPTP (1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine)-treated mice, a model of parkinsonism. These findings
      complement others suggesting NIr treatment protects against damage from various
      insults. However one puzzling feature of NIr treatment is that unilateral
      exposure can lead to a bilateral healing response, suggesting NIr may have
      'indirect' protective effects. We investigated whether remote NIr treatment is
      neuroprotective by administering different MPTP doses (50-, 75-, 100-mg/kg) to
      mice and treating with 670-nm light directed specifically at either the head or
      body. Our results show that, despite no direct irradiation of the damaged tissue,
      remote NIr treatment produces a significant rescue of tyrosine hydroxylase
      positive cells in the substantia nigra pars compacta at the milder MPTP dose of
      50-mg/kg (~30% increase vs sham-treated MPTP mice, p<0.05). However this
      protection did not appear as robust as that achieved by direct irradiation of the
      head (~50% increase vs sham-treated MPTP mice, p<0.001). There was no
      quantifiable protective effect of NIr at higher MPTP doses, irrespective of the
      delivery mode. Astrocyte and microglia cell numbers in substantia nigra pars
      compacta were not influenced by either mode of NIr treatment. In summary, the
      findings suggest that treatment of a remote tissue with NIr is sufficient to
      induce protection of the brain, reminiscent of the 'abscopal effect' sometimes
      observed in radiation treatment of metastatic cancer. This discovery has
      implications for the clinical translation of light-based therapies, providing an
      improved mode of delivery over transcranial irradiation. 

PMID- 24857853
TI  - Beneficial influence of physical exercise following status epilepticus in the
      immature brain of rats.
AB  - Studies in adult animals have demonstrated a beneficial effect of physical
      exercise on epileptic insults. Although the effects of physical exercise on the
      mature nervous system are well documented, its influence on the developing
      nervous system subjected to injuries in childhood has been little explored. The
      purpose of our study was to investigate whether a physical exercise program
      applied during brain development could influence the hippocampal plasticity of
      rats submitted to status epilepticus (SE) induced by pilocarpine model at two
      different ages of the postnatal period. Male Wistar rats aged 18 (P18) and 28
      (P28) days were randomly divided into four groups: Control (CTRL), Exercise (EX),
      SE (SE) and SE Exercise (SE/EX) (n=17 per group). After the aerobic exercise
      program, histological and behavioral (water maze) analyses were performed. Our
      results showed that only animals subjected to pilocarpine-induced SE at P28
      presented spontaneous seizures during the observational period. A significant
      reduction in seizure frequency was observed in the SE/EX group compared to the SE
      group. In adulthood, animals submitted to early-life SE displayed impairment in
      long-term memory in the water maze task, while the exercise program reversed this
      deficit. Reduced mossy fiber sprouting in the dentate gyrus was noted in animals
      that presented spontaneous seizures (SE/EX vs SE). Exercise increased cell
      proliferation (Ki-67 staining) and anti-apoptotic response (bcl-2 staining) and
      reduced pro-apoptotic response (Bax staining) in animals of both ages of SE
      induction (P18/28). Exercise also modified the brain-derived neurotrophic factor
      (BDNF) levels in EX and SE/EX animals. Our findings indicate that in animals
      subjected to SE in the postnatal period a physical exercise program brings about
      beneficial effects on seizure frequency and hippocampal plasticity in later
      stages of life. 

PMID- 24857854
TI  - Early aortic repair worsens concurrent traumatic brain injury.
AB  - BACKGROUND: Blunt thoracic aortic injury (BTAI) and traumatic brain injury (TBI)
      are the leading causes of death after blunt trauma, and TBI is common among
      patients with BTAI. Although aspects of aortic management, such as repair timing
      and procedural anticoagulation therapy, may complicate TBI, the optimal
      management of these patients is undefined. METHODS: Adults with BTAI and moderate
      to severe TBI admitted to a level I trauma center over 12 years were
      retrospectively analyzed; patients presenting in extremis were excluded. The
      primary outcome was neurologic progression within 48 hours of aortic repair.
      Patients undergoing nonoperative aortic management served as controls for
      baseline TBI progression. Secondary outcomes were aortic morbidity and mortality
      and overall inpatient survival. RESULTS: Of 309 patients with BTAI, 138 had
      concurrent TBI, and 75 were included for analysis. Twenty-two (29%) were treated
      nonoperatively, 29 (39%) had early aortic repair (17 open, 12 endovascular), and
      24 (32%) had delayed repair (3 open, 21 endovascular). The severity of TBI was
      similar between groups. Early aortic repair within 24 hours of admission was
      independently associated with worsening TBI, regardless of repair modality or
      anticoagulation use. In contrast, patients undergoing delayed repair had no
      perioperative neurologic progression despite procedural anticoagulation therapy.
      Early aortic repair was also associated with increased aortic morbidity and
      mortality. CONCLUSIONS: For patients with BTAI and TBI, early aortic intervention
      is associated with progressive TBI regardless of repair modality, as well as
      increased aortic morbidity and mortality. Patients not requiring emergent
      intervention can undergo delayed repair with full anticoagulation therapy.

PMID- 24857855
TI  - Postoperative local morbidity and the use of vacuum-assisted closure after
      complex chest wall reconstructions with new and conventional materials.
AB  - BACKGROUND: New materials (NM) such as titanium plates, cryopreserved grafts, and
      acellular collagen matrices are being increasingly used for chest wall
      reconstruction as a result of improved incorporation while maintaining structural
      stability and reduced need for removal from infected areas. Direct comparisons
      between NM and conventional materials (CM) in terms of local morbidity and need
      for prosthesis removal are lacking. METHODS: Between January 2005 and July 2013,
      109 procedures were performed to remove chest wall tumors in 86 patients. Of
      these, 32 underwent complex chest wall reconstructions owing to either
      recurrence, defect extension (greater than 3 ribs or >100 cm2) or local
      conditions (ie, previous irradiation or infection). New materials and CM (ie,
      polytetrafluoroethylene and methyl methacrylate) were used in 17 (53%) and 15
      (47%) patients, respectively. Of the 32 patients included in the high complexity
      group, 23 patients did not exhibit any postoperative complications (72%).
      However, 9 patients (28%) underwent both a first and a second reoperation after a
      median interval of 4 months from the first procedure (range, 7 days to 60
      months). Vacuum-assisted closure (VAC) was instituted in all patients as a means
      to control sepsis and facilitate space obliteration with healthy tissue. RESULTS:
      In 7 patients the reason for reintervention was local wound complications. In 4
      of 7 patients, the prosthesis had to be removed (3 CM and 1 NM, 4.6% of the whole
      series; 12.5% in the high complexity group, 5.9% for NM and 20% for CM). The
      median time to complete chest wall healing after VAC in patients with local
      sepsis was 14 months (range, 5 to 60 months). All patients are currently alive
      and well except for 1 who died 11 months after complete chest wall healing as a
      result of dissemination of metastatic chondrosarcoma. At univariate analysis,
      predictors of overall and grade 2 or less morbidity according to the Common
      Terminology Criteria for Adverse Events version 4.0 were first (p=0.038) and
      second (p=0.015) redo operations. Conversely, patients with a body mass index of
      less than 25 kg/m2 (p=0.049) undergoing one (p=0.032) or two reconstructions
      (p=0.00047) with combined materials (p=0.00029) were more likely to experience
      local wound complications and require VAC. On multiple regression analysis, redo
      operations (first, p=0.032; second, p=0.00047) and the use of combined (synthetic
      and biologic) materials (p=0.0029) were confirmed to be related to an increased
      incidence of wound complications. CONCLUSIONS: Multiple redo operations after
      complex chest wall reconstruction performed with a combination of NM and CM may
      be associated with an increased incidence of local wound complications.
      Nevertheless, in these cases, the use of NM and VAC yielded a low rate (5.8%
      versus 20% with CM) of prosthesis removal while achieving complete wound healing.

PMID- 24857856
TI  - Superhydrophobic ceramic coatings enabled by phase-separated nanostructured
      composite TiO2-Cu2O thin films.
AB  - By exploiting phase-separation in oxide materials, we present a simple and
      potentially low-cost approach to create exceptional superhydrophobicity in thin
      film based coatings. By selecting the TiO2-Cu2O system and depositing through
      magnetron sputtering onto single crystal and metal templates, we demonstrate
      growth of nanostructured, chemically phase-segregated composite films. These
      coatings, after appropriate chemical surface modification, demonstrate a robust,
      non-wetting Cassie-Baxter state and yield an exceptional superhydrophobic
      performance, with water droplet contact angles reaching to ~172 degrees  and
      sliding angles <1 degrees . As an added benefit, despite the photo-active nature
      of TiO2, the chemically coated composite film surfaces display UV stability and
      retain superhydrophobic attributes even after exposure to UV (275 nm) radiation
      for an extended period of time. The present approach could benefit a variety of
      outdoor applications of superhydrophobic coatings, especially for those where
      exposure to extreme atmospheric conditions is required.

PMID- 24857857
TI  - RELAXIN enhances differentiation and matrix mineralization through
      Relaxin/insulin-like family peptide receptor 2 (Rxfp2) in MC3T3-E1 cells in
      vitro.
AB  - RELAXIN (RLN) is a polypeptide hormone of the insulin-like hormone family; it
      facilitates birth by softening and widening the pubic symphysis and cervix in
      many mammals, including humans. The role of RLN in bone metabolism was recently
      suggested by its ability to induce osteoclastogenesis and activate osteoclast
      function. RLN binds to RELAXIN/INSULIN-LIKE FAMILY PEPTIDE 1 (RXFP1) and 2
      (RXFP2), with varying species-specific affinities. Young men with mutated RXFP2
      are at high risk for osteoporosis, as RXFP2 influences osteoblast metabolism by
      binding to INSULIN-LIKE PEPTIDE 3 (INSL3). However, there have been no reports on
      RLN function in osteoblast differentiation and mineralization or on the
      functionally dominant receptors for RLN in osteoblasts. We previously described
      Rxfp1 and 2 expression patterns in developing mouse oral components, including
      the maxillary and mandibular bones, Meckel's cartilage, tongue, and tooth
      primordia. We hypothesized that Rln/Rxfp signaling is a key mediator of skeletal
      development and metabolism. Here, we present the gene expression patterns of
      Rxfp1 and 2 in developing mouse calvarial frontal bones as determined by in situ
      hybridization. In addition, RLN enhanced osteoblastic differentiation and caused
      abnormal mineralization and extracellular matrix metabolism through Rxfp2, which
      was predominant over Rxfp1 in MC3T3-E1 mouse calvarial osteoblasts. Our data
      suggest a novel role for Rln in craniofacial skeletal development and metabolism
      through Rxfp2. 

PMID- 24857858
TI  - Trabecular bone recovers from mechanical unloading primarily by restoring its
      mechanical function rather than its morphology.
AB  - Upon returning to normal ambulatory activities, the recovery of trabecular bone
      lost during unloading is limited. Here, using a mouse population that displayed a
      large range of skeletal susceptibility to unloading and reambulation, we tested
      the impact of changes in trabecular bone morphology during unloading and
      reambulation on its simulated mechanical properties. Female adult mice from a
      double cross of BALB/cByJ and C3H/HeJ strains (n=352) underwent 3wk of hindlimb
      unloading followed by 3wk of reambulation. Normally ambulating mice served as
      controls (n=30). As quantified longitudinally by in vivo MUCT, unloading led to
      an average loss of 43% of trabecular bone volume fraction (BV/TV) in the distal
      femur. Finite element models of the MUCT tomographies showed that deterioration
      of the trabecular structure raised trabecular peak Von-Mises (PVM) stresses on
      average by 27%, indicating a significant increase in the risk of mechanical
      failure compared to baseline. Further, skewness of the Von-Mises stress
      distributions (SVM) increased by 104% with unloading, indicating that the
      trabecular structure became inefficient in resisting the applied load. During
      reambulation, bone of experimental mice recovered on average only 10% of its lost
      BV/TV. Even though the addition of trabecular tissue was small during
      reambulation, PVM and SVM as indicators of risk of mechanical failure decreased
      by 56% and 57%, respectively. Large individual differences in the response of
      trabecular bone, together with a large sample size, facilitated stratification of
      experimental mice based on the level of recovery. As a fraction of all mice, 66%
      of the population showed some degree of recovery in BV/TV while in 89% and 87% of
      all mice, PVM and SVM decreased during reambulation, respectively. At the end of
      the reambulation phase, only 8% of the population recovered half of the unloading
      induced losses in BV/TV while 50% and 49% of the population recovered half of the
      unloading induced deterioration in PVM and SVM, respectively. The association
      between morphological and mechanical variables was strong at baseline but
      progressively decreased during the unloading and reambulation cycles. The
      preferential recovery of trabecular micromechanical properties over bone volume
      fraction emphasizes that mechanical demand during reambulation does not, at least
      initially, seek to restore bone's morphology but its mechanical integrity. 

PMID- 24857860
TI  - The ever changing moods of calmodulin: how structural plasticity entails
      transductional adaptability.
AB  - The exceptional versatility of calmodulin (CaM) three-dimensional arrangement is
      reflected in the growing number of structural models of CaM/protein complexes
      currently available in the Protein Data Bank (PDB) database, revealing a great
      diversity of conformations, domain organization, and structural responses to
      Ca(2+). Understanding CaM binding is complicated by the diversity of target
      proteins sequences. Data mining of the structures shows that one face of each of
      the eight CaM helices can contribute to binding, with little overall difference
      between the Ca(2+) loaded N- and C-lobes and a clear prevalence of the C-lobe low
      Ca(2+) conditions. The structures reveal a remarkable variety of configurations
      where CaM binds its targets in a preferred orientation that can be reversed and
      where CaM rotates upon Ca(2+) binding, suggesting a highly dynamic metastable
      relation between CaM and its targets. Recent advances in structure-function
      studies and the discovery of CaM mutations being responsible for human diseases,
      besides expanding the role of CaM in human pathophysiology, are opening new
      exciting avenues for the understanding of the how CaM decodes Ca(2+)-dependent
      and Ca(2+)-independent signals. 

PMID- 24857861
TI  - Factors influencing compact-extended structure equilibrium in oligomers of abeta1
      40 peptide--an ion mobility mass spectrometry study.
AB  - Oligomers formed by amyloid beta (Abeta) peptide are widely believed to be the
      main neurotoxic agent in Alzheimer's disease. Studies discovered a broad variety
      of oligomeric forms, which display different levels of toxicity. Some of these
      forms may further assemble into mature fibrils, while other might be off-pathway
      from conversion to fibrils and assemble into alternative forms. To better
      understand a relationship between the structure and toxicity of Abeta oligomers,
      we require systematic characterization and classification of all possible forms,
      facilitating rational design of the beneficial modifiers of their activity. In
      previous ion mobility analysis of Abeta1-40 oligomers, we have detected the
      coexistence of two alternative structural forms (compact and extended) in a pool
      of low-order Abeta1-40 oligomers. These forms may represent two pathways of the
      oligomer evolution, leading either to fibrils or to off-pathway oligomers, which
      are potential candidates for the neurotoxic species. Here, we have analyzed the
      impact of incubation time, the presence of selected metal ions and the effect of
      a series of point mutations on mutual population of alternative forms. We have
      shown that a salt bridge D23K28 provides stabilization of the compact form
      whereas G25 is required for the existence of the extended form. We have found
      that binding of metal ions also stabilizes the compact form. These results
      improve our understanding of the possible molecular mechanism of the bifurcation
      of structural evolution of non-monomeric Abeta species into an off-fibril
      pathway, ultimately leading to the formation of potentially neurotoxic species. 

PMID- 24857859
TI  - New applications for phage integrases.
AB  - Within the last 25 years, bacteriophage integrases have rapidly risen to
      prominence as genetic tools for a wide range of applications from basic cloning
      to genome engineering. Serine integrases such as that from phiC31 and its
      relatives have found an especially wide range of applications within diverse
      micro-organisms right through to multi-cellular eukaryotes. Here, we review the
      mechanisms of the two major families of integrases, the tyrosine and serine
      integrases, and the advantages and disadvantages of each type as they are applied
      in genome engineering and synthetic biology. In particular, we focus on the new
      areas of metabolic pathway construction and optimization, biocomputing,
      heterologous expression and multiplexed assembly techniques. Integrases are
      versatile and efficient tools that can be used in conjunction with the various
      extant molecular biology tools to streamline the synthetic biology production
      line. 

PMID- 24857862
TI  - The P2X7 receptor: shifting from a low- to a high-conductance channel - an
      enigmatic phenomenon?
AB  - The general structure of the P2X7 receptor (P2X7R) is similar to the structure of
      other P2X receptor family members, with the exception of its C terminus, which is
      the longest of this family. The P2X7R activates several intracellular signaling
      cascades, such as the calmodulin, mitogen-activated protein kinase and
      phospholipase D pathways. At low concentrations of ATP (micromolar range), P2X7R
      activation opens a cationic channel, similarly to other P2X receptors. However,
      in the presence of high concentrations of ATP (millimolar range), it opens a
      pathway that allows the passage of larger organic cations and anions. Here, we
      discuss both the structural characteristics of P2X7R related to its remarkable
      functions and the proposed mechanisms, including the dilation of the endogenous
      pore and the integration of another channel. In addition, we highlight the
      importance of P2X7R as a therapeutic target. 

PMID- 24857863
TI  - Immunological enhancement action of endotoxin-free tilapia heat shock protein 70
      against Streptococcus iniae.
AB  - The immunological effects of heat shock proteins (HSPs) had been found in humans
      and mice, but scarce data of endotoxin-free Hsp70 were reported in tilapia. In
      the current study, we reported that tHsp70 alone and antigen-tHsp70 compound
      increased the proliferations of lymphocytes and macrophages, significantly
      increased the NO release and phagocytotic ability of macrophages (p<0.05), and
      enhanced the levels of immune-related genes in lymphocytes and macrophages in a
      dose- and/or time-dependent manner. On the other hand, tHsp70 not only helped to
      reduce the proliferation inhibitions induced by the ECP treatment, but also
      assisted antigens to enhance the vaccine-induced protection against Streptococcus
      iniae (p<0.05). We described, for the first time, a critical role of endotoxin
      free tHsp70 on activation of tilapia lymphocytes and macrophages post S. iniae
      exposure and its up-regulation effects on vaccine-induced protection. Our
      research highlights the immunological enhancement action of Hsp70 in teleost
      immunity.

PMID- 24857864
TI  - Pre-clinical evaluation of [(68)Ga]Ga-DO3A-VS-Cys(40)-Exendin-4 for imaging of
      insulinoma.
AB  - INTRODUCTION: Insulinoma is the most common form of pancreatic endocrine tumors
      responsible for hyperinsulinism in adults. These tumors overexpress glucagon like
      peptide-1 (GLP-1) receptor, and biologically stable GLP-1 analogs have therefore
      been proposed as potential imaging agents. Here, we evaluate the potential of a
      positron emission tomography (PET) tracer, [(68)Ga]Ga-DO3A-VS-Cys(40)-Exendin-4,
      for imaging and quantification of GLP-1 receptors (GLP-1R) in insulinoma.
      METHODS: [(68)Ga]Ga-DO3A-VS-Cys(40)-Exendin-4 was evaluated for binding to GLP-1R
      by in vitro autoradiography binding studies in INS-1 tumor from xenografts. In
      vivo biodistribution was investigated in healthy control mice, INS-1 xenografted
      and PANC1 xenografted immunodeficient mice at two different doses of peptide:
      2.5MUg/kg (baseline) and 100MUg/kg (block). In vivo imaging of [(68)Ga]Ga-DO3A-VS
      Cys(40)-Exendin-4 in xenografted mice was evaluated by small animal PET/CT using
      a direct comparison with the clinically established insulinoma marker [(11)C]5
      hydroxy-tryptophan ([(11)C]5-HTP). RESULTS: GLP-1 receptor density could be
      quantified in INS-1 tumor biopsies. [(68)Ga]Ga-DO3A-VS-Cys(40)-Exendin-4 showed
      significant uptake (p<=0.05) in GLP1-R positive tissues such as INS-1 tumor,
      lungs and pancreas upon comparison between baseline and blocking studies. In vivo
      imaging showed concordant results with higher tumor-to-muscle ratio in INS-1
      xenografted mice compared with [(11)C]5-HTP. CONCLUSION: [(68)Ga]Ga-DO3A-VS
      Cys(40)-Exendin-4 has high affinity and specificity for GLP-1R expressed on
      insulinoma in vitro and in vivo.

PMID- 24857865
TI  - A radiometabolite study of the serotonin transporter PET radioligand
      [(11)C]MADAM.
AB  - INTRODUCTION: (11)C]MADAM is a radioligand suitable for PET studies of the
      serotonin transporter (SERT). Metabolite analysis in human and non-human plasma
      samples using HPLC separation has shown that [(11)C]MADAM was rapidly
      metabolized. A possible metabolic pathway is the S-oxidation which could lead to
      SOMADAM and SO2MADAM. In vitro evaluation of these two potential metabolites has
      shown that SOMADAM exhibited a good affinity for SERT and a good selectivity for
      SERT over NET and DAT. METHODS: Comparative PET imaging studies in non-human
      primate brain with [(11)C]MADAM and [(11)C]SOMADAM were carried out, and plasma
      samples were analyzed using reverse phase HPLC. We have explored the metabolism
      of [(11)C]MADAM in rat brain with a view to understand its possible interference
      for brain imaging with PET. RESULTS: PET imaging studies in non-human primate
      brain using [(11)C]SOMADAM indicated that this tracer does not bind with high
      amounts to brain regions known to be rich in SERT. The fraction of [(11)C]SOMADAM
      in non-human primate plasma was approximately 5% at 4min and 1% at 15min after
      [(11)C]MADAM injection. HPLC analysis of brain sample after [(11)C]MADAM
      injection to rats demonstrated that [(11)C]SOMADAM was not detected in the brain.
      CONCLUSIONS: (11)C]SOMADAM is not superior over [(11)C]MADAM as a SERT PET
      radioligand. Nevertheless, [(11)C]SOMADAM has been identified as a minor labeled
      metabolite of [(11)C]MADAM measured in monkey plasma. [(11)C]SOMADAM was not
      detected in rat brain.

PMID- 24857866
TI  - (11)C-Labeling of a potent hydroxyethylamine BACE-1 inhibitor and evaluation in
      vitro and in vivo.
AB  - INTRODUCTION: The enzyme beta-secretase 1 (BACE-1) is associated with the
      catalytic cleavage of amyloid precursor protein (APP) which leads to the
      production of amyloid-beta, an amyloidogenic peptide that forms insoluble fibrils
      and is linked to neurodegeneration and Alzheimer's disease (AD). A PET
      radioligand for the quantification of BACE-1 would be useful for the
      understanding of AD. In this report, we describe the synthesis and carbon-11
      radiolabeling of a potent hydroxyethylamine BACE-1 enzyme inhibitor (BSI-IV) and
      its evaluation in vitro and in vivo. METHODS: (11)[C]-N(1)-((2S,3R)-4
      (cyclopropylamino)-3-hydroxy-1-phenylbutan-2-yl)-5-(N-methylmethyl-sulfonamido)
      N(3)-((R)-1-phenylethyl)isophthalamide, a beta-secretase inhibitor, denoted here
      as [(11)C]BSI-IV was synthesized through a palladium-mediated aminocarbonylation
      with an aryl halide precursor (I or Br) and [(11)C]CO. The effect of different
      palladium/ligand-complexes on radiochemical yield in the carbonylative reaction
      was investigated. The binding of the labeled compound to BACE-1 enzyme was
      studied in vitro by frozen section autoradiography from brains of healthy rats.
      Dynamic small animal PET-CT studies and ex vivo biodistribution were performed in
      male rats. RESULTS: The halide precursors were synthesized in six steps starting
      from methyl-3-nitrobenzoate with an overall yield of 21-26%. [(11)C]BSI-IV was
      obtained in 29+/-12% decay corrected radiochemical yield (n=12) with a specific
      activity of 790+/-155GBq/MUmol at the end of synthesis with a radiochemical
      purity of >99%. The preclinical studies showed that [(11)C]BSI-IV has a rapid
      metabolism in rat with excretion to the small intestines. CONCLUSION: (11)[C]BSI
      IV was obtained in sufficient amount and purity to enable preclinical
      investigation. The preclinical studies showed low specific binding in vitro and
      fast clearance in vivo and a low uptake in the brain. These findings suggests
      that [(11)C]BSI-IV has limited use as a PET-ligand for the study of BACE-1 or AD.

PMID- 24857867
TI  - Selenium-dependent antitumor immunomodulating activity of polysaccharides from
      roots of A. membranaceus.
AB  - Roots of Astragalus membranaceus (Fish.) Bge. var. mongholicus (Bge.) Hsiao (A.
      membranaceus) have been long used as an auxiliary reagent supporting cancer
      treatment. Here, we compared the chemical composition and antitumor
      immunomodulating activity of polysaccharides from roots of A. membranaceus (PAMs)
      from five major habitats in Inner Mongolia, PR China. We revealed that
      compositions of monosaccharides and amino acids were comparable among PAMs from
      different habitats. However, amounts of selenium varied widely in roots of A.
      membranaceus and PAMs. PAMs selenium-dependently repressed the in vivo
      proliferation of transplanted H22 ascitic hepatoma and S180 sarcoma cells with
      low toxic impacts on tumor-bearing mice. Selenium-containing PAMs ameliorated
      host CD4+ T cell apoptosis and serum cytokine dysregulation induced by tumor
      transplantation, leading to the enhancement of cytotoxic activities of natural
      killer and CD8+ T cells. Moreover, PAMs also selenium-dependently improved the
      phagocytotic function of intra-abdominal macrophages and suppressed M2-like
      polarization of tumor-associated macrophages. These data suggested that the
      selenium content varies in the roots of A. membranaceus and PAMs from different
      geographical origins dramatically and selenium is an important contributor to the
      antitumor immunomodulation activities of PAMs. 

PMID- 24857868
TI  - Synthesis and characterization of antimicrobial crosslinked carboxymethyl
      chitosan nanoparticles loaded with silver.
AB  - Carboxymethyl chitosan (CMCh)-silver nanoparticle (Ag) hydrogels with high
      antibacterial activity against three Gram +ve bacteria (Staphylococcus aureus,
      Bacillus subtilis and Streptococcus faecalis), three Gram -ve bacteria
      (Escherichia coli, Pseudomonas aeruginosa and Neisseria gonorrhoeae) and a
      Candida albicans fungus were prepared. The in situ preparation reaction involved
      crosslinking of CMCh with epichlorohydrin in alkaline medium containing silver
      nitrate to yield silver nanoparticles loaded CMCh hydrogel giving pale brown or
      darker hydrogels when the silver content increases. FTIR spectroscopy, SEM and
      TEM were done for the prepared hydrogels. Silver nanoparticles hydrogels
      exhibited higher antimicrobial activity than virgin CMCh. TEM analysis showed the
      small size of the prepared hydrogels to be in the range of 9-16nm in size. 

PMID- 24857869
TI  - Preparation of chitin nanofiber-reinforced carboxymethyl cellulose films.
AB  - In this study, we investigated the preparation of chitin nanofiber (CNF)
      reinforced carboxymethyl cellulose (CMC) films by their electrostatic
      interaction. First, CMC films and self-assembled CNF dispersions with methanol
      were prepared by casting technique and regeneration from chitin ion gels with an
      ionic liquid, respectively. Then, the CMC films were immersed in the dispersions
      with the different CNF contents, followed by centrifugation to obtain the desired
      composite films. The amounts of the absorbed CNFs on the films were calculated by
      the weight increases after the above compatibilization procedure. The presence of
      CNFs on the films was also confirmed by the SEM and IR measurements. The
      mechanical properties of the composite films were evaluated by tensile testing,
      which suggested the reinforcing effect of CNFs present on the CMC films. 

PMID- 24857870
TI  - Microencapsulation of lectin anti-cancer agent and controlled release by alginate
      beads, biosafety approach.
AB  - Hepatocellular carcinoma (HCC) is considered as one of the most aggressive cancer
      worldwide. In Egypt, the prevalence of HCC is increasing during last years.
      Recently, drug-loaded microparticles were used to improve the efficiency of
      various medical treatments. This study is designed to evaluate the anticancer
      potentialities of lectins against HCC while hinting to its safety usage. The aim
      is also extended to encapsulate lectins in alginate microbeads for oral drug
      delivery purposes. The extracted lectins showed anti-proliferative effect against
      HCC with a percentage of 60.76% by using its nontoxic dose with an up-regulation
      of P53 gene expression. Concerning the handling of lectin alginate microbeads for
      oral drug delivery, the prepared lectin alginate beads were ~100MUm in diameter.
      The efficiency of the microcapsules was checked by scanning electron microscopy,
      the SEM showed the change on the alginate beads surface revealing the successful
      lectin encapsulation. The release of lectins from the microbeads depended on a
      variety of factors as the microbeads forming carriers and the amount-encapsulated
      lectins. The Pisum sativum extracted lectins may be considered as a promising
      agent in controlling HCC and this solid dosage form could be suitable for oral
      administration complemented with/or without the standard HCC drugs. 

PMID- 24857871
TI  - Screening and comparison of antioxidant activities of polysaccharides from
      Coriolus versicolor.
AB  - Six polysaccharide fractions (Coriolus versicolor polysaccharides: CVPS-1, CVPS
      2, CVPS-3, CVPS-4, CVPS-5 and CVPS-6) were isolated and purified from the
      fruiting bodies of C. versicolor by ion exchange chromatography and gel
      chromatography. Their chemical and physical characteristics were determined by
      chemical methods, high performance liquid chromatography, and high-performance
      gel-permeation chromatography. Finally, 1,1-diphenyl-2-picrylhydrazyl (DPPH)
      radical assay, superoxide radical assay, and hydroxyl radical assay were carried
      out to test the antioxidant activities of CVPS in vitro. The results indicated
      that the six CVPS fractions were acidic heteropolysaccharides, composed of
      mannose, rhamnose, glucuronic acid, glucose and fructose with different ratios.
      The molecular weights of CVPS-1, CVPS-2, CVPS-3, CVPS-4, CVPS-5 and CVPS-6 were
      1740, 1480, 568, 880, 1260 and 1840kDa and the protein contents were 4.2%, 6.4%,
      8.5%, 7.8%, 6.5% and 3.9%, respectively. Among the six fractions, CVPS with lower
      molecular weight, higher protein content and larger uronic acid amount, basically
      exhibited higher radical scavenging effects at the same concentration. Compared
      with other fractions, CVPS-3 exhibited the highest antioxidant activities. The
      effects of the molecular weight, protein content and uronic acid amount of the
      polysaccharides appeared to be significant on the improvement of the
      bioactivities. 

PMID- 24857872
TI  - Variation in the structural changes of myoglobin in the presence of several
      protic ionic liquid.
AB  - Protein stability in ionic solution depends on the delicate balance between
      protein-ion and ion-ion interactions. To address the ion specific effects on the
      protein, we have examined the stability of myoglobin (Mb) in the presence of
      buffer and ammonium-based ionic liquids (ILs) (50%, v/v). Here, fluorescence and
      circular dichroism (CD) spectroscopy experiments are used to study the influence
      of ILs on structure and stability of Mb. Our experimental results reveal that
      more viscous ILs (sulphate or phosphate ions) are stabilizers and therefore more
      biocompatible for Mb structure. Surprisingly, the less viscous ILs such as
      acetate anion based ILs are destabilizers for the native structure of Mb. Our
      results explicitly elucidate that anion variation has significant influence on Mb
      stability efficiency than cation variation. This study provides insight into
      anion effects on protein stability and explains that the intrasolvent
      interactions can be leveraged to enhance the stability. 

PMID- 24857873
TI  - Bioadhesive tablets containing cyclodextrin complex of itraconazole for the
      treatment of vaginal candidiasis.
AB  - Itraconazole (ITR) is commonly used in the treatment of Candida infections. It
      has a nephrotoxic effect and low bioavailability in patients who suffer from
      renal insufficiency, and its poor solubility in water makes ITR largely
      unavailable. Cyclodextrins (CyDs) are used to form inclusion complexes with drugs
      to improve their aqueous solubility and to reduce their side effects. In this
      study, ITR was complexed with gamma-cyclodextrin (gamma-CyD), hydroxypropyl-beta
      cyclodextrin (HP-beta-CyD), methyl-beta-cyclodextrin (Met-beta-CyD) and
      sulphobutyl ether-beta-cyclodextrin (SBE7-beta-CyD) to increase its water
      solubility and to reduce the side effects of the drug without decreasing
      antifungal activity. Complex formation between ITR and CyDs was evaluated using
      SEM, (1)H NMR and XRD studies. The antifungal activity of the complexes was
      analyzed on Candida albicans strains, and the susceptibility of the strains was
      found to be higher for the ITR-SBE7-beta-CyD complex than for the complexes that
      were prepared with other CyDs. Vaginal bioadhesive sustained release tablet
      formulations were developed using the ITR-SBE7-beta-CyD inclusion complex to
      increase the residence time of ITR in the vagina, thereby boosting the efficacy
      of the treatment. The swelling, matrix erosion and bioadhesion properties of
      formulations and the drug release rate of these tablets were analyzed, and the
      most therapeutically effective vaginal formulation was determined. 

PMID- 24857874
TI  - Antitussive arabinogalactan of Andrographis paniculata demonstrates synergistic
      effect with andrographolide.
AB  - Traditional Indian medicines have been used in humans for thousands of years.
      While the link to a particular indication has been established in man, the active
      principle of the formulations often remains unknown. In this study, we aim to
      investigate the structural features and antitussive activity of fractions from
      Andrographis paniculata leaves. In vivo investigations of water extract (WE), and
      both ethanol-soluble (WES) and precipitated (WEP) fractions from WE on the citric
      acid induced cough efforts and airways smooth muscle reactivity in guinea pigs
      were performed. Chemical, chromatographic and spectroscopic analysis revealed the
      existence of a highly branched pectic arabinogalactan (109kDa) in WEP and
      andrographolide in WES. WEP showed significant antitussive activity while the
      potencies of WE and WES are even higher. Neither WE nor WES significantly alter
      specific airway smooth muscle reactivity. Remarkably, the antitussive activity of
      arabinogalactan could be increased by synergistic action with andrographolide.
      Finally, traditional aqueous extraction method provides an arabinogalactan from
      A. paniculata, which stimulate biological response but without addiction. 

PMID- 24857875
TI  - Physicochemical and release characteristics of acetylated Indian palmyrah
      retrograded shoot starch.
AB  - The aim of the present study is to determine the influence of serial
      modifications, including retrogradation followed by acetylation on morphological,
      physicochemical and drug release properties of retrograded Indian palmyrah
      (Borassus flabellifer L.) shoot starch. The acetylated retrograded starches
      prepared by using different concentrations of acetic anhydride were shown a
      degree of substitution (DS) in the range of 0.16-0.55. Acetylation of retrograded
      starch produced significant morphological changes from rough to smooth surface.
      The amylose content, water holding capacity, swelling and solubility power tend
      to increase with increase in DS. A strong peak at 1751 and 1032cm(-1) confirms
      the formation of acetylated retrograded starch. The TGA data reveal that with
      increase in DS there is an increased thermal stability and decreased bound water
      of starch. The elemental analysis also confirms the addition of acetyl groups
      because of increased carbon and hydrogen content. The matrix tablets of
      acetylated retrograded starch with high DS showed a delayed release in gastric pH
      and sustained release in simulated intestinal fluid. Overall, this result
      suggested that acetylated retrograded starch with high DS are thermally stable
      and can be used for formulating protein and peptide drugs for colon targeting. 

PMID- 24857876
TI  - Comparative studies on the heterogeneity of plasma-derived and recombinant human
      albumins in laboratory use.
AB  - We investigated the thiol-redox state, and the relationship between structural
      characteristics, such as thermal stability, and functional properties, such as
      cell growth activity, of commercial plasma-derived (pHSA) and recombinant human
      serum albumin (rHSA) products. In this study, 5 pHSA products (A1653, A9511,
      A1887, A8763, and A3782) and 2 rHSA products (A9731 and A9986) were obtained from
      Sigma-Aldrich. Among them, three kinds of HSA products [A1653 (an initial
      fractionation product), A3782 (a final purified product), and A9731 (recombinant
      albumin expressed in rice)] were selected for experiments on the thermal
      stabilities, analyzed by thermal denaturation curves, and cell growth activities
      of U937 and THP-1 cell lines using the WST-1 reagent. The secondary and tertiary
      structures of HSA products were similar, whereas a marked difference was observed
      in their thermal stabilities. The degree of thermal stability of the three
      representative products was in the order of A9731 (rHSA)>A1653 (pHSA)>A3782
      (pHSA), as was the degree of cell growth activity of these products. One possible
      explanation for the present results is that albumin-bound fatty acids may have
      influenced the thermal stabilities and cell growth activities of U937 and THP-1
      cells. 

PMID- 24857877
TI  - A food additive with prebiotic properties of an alpha-d-glucan from lactobacillus
      plantarum DM5.
AB  - An alpha-d-glucan produced by Lactobacillus plantarum DM5 was explored for in
      vitro prebiotic activities. Glucan-DM5 demonstrated 21.6% solubility, 316.9%
      water holding capacity, 86.2% flocculation activity, 71.4% emulsification
      activity and a degradation temperature (Td) of 292.2 degrees C. Glucan-DM5
      exhibited lowest digestibility of 0.54% by artificial gastric juice, 0.21% by
      intestinal fluid and 0.32% by alpha-amylase whereas the standard prebiotic
      inulin, showed 25.23%, 5.97% and 19.13%, hydrolysis, respectively. Prebiotic
      activity assay of glucan-DM5 displayed increased growth of probiotic bacteria
      such as Bifidobacterium infantis and Lactobacillus acidophilus, but did not
      support the growth of non-probiotic bacteria such as Escherichia coli and
      Enterobacter aerogenes. The overall findings indicated that glucan from L.
      plantarum DM5 can serve as a potential prebiotic additive for food products. 

PMID- 24857878
TI  - Keratinolytic proteinase from Bacillus thuringiensis AD-12.
AB  - A new isolated strain noted to produce a novel detergent-stable serine
      keratinolytic proteinase and identified as Bacillus thuringiensis AD-12. Native
      keratinolytic proteinase from B. thuringiensis (BtKER) was purified and
      characterized. The purified BtKER enzyme is a monomer with a molecular mass of
      39kDa. Biochemical characterization assays revealed that the BtKER attained
      optimal activity at pH 7 and 30 degrees C. Residual activity after 1h incubation
      at 50 degrees C was higher than 80%. The enzyme was activated and stabilized by
      Mn(2+) and Li(+) metal ions but inactivated by organic solvents. Purified BtKER
      showed the highest substrate specificity toward keratin from wool>sodium
      caseinate>collagen>BSA>gelatin in descending order. BtKER is the first reported
      keratinolytic proteinase from B. thuringiensis and obtained results suggested
      that new characterized enzyme can be a powerful biocatalyst in peptide production
      associated to hydrolysis of keratinous and/or keratin-like waste. 

PMID- 24857879
TI  - A Salmonella enterica conjugative plasmid impairs autophagic flux in infected
      macrophages.
AB  - pR(ST98) was originally isolated from Salmonella enterica serovar typhi and could
      be transferred among enteric bacilli by conjugation. Our previous studies
      indicated that it could intervene in autophagy of host cells, while the mechanism
      remained undefined. Here, we explored how pR(ST98) influenced the autophagic flux
      of murine macrophage-like cell line (J774A.1). S. enterica serovar typhimurium
      wild type strain (chi3306), harboring a 100 kb virulence plasmid, was used as a
      positive control. pR(ST98) was transferred into chi3306 virulence plasmid cured
      strain (chi3337) to create the transconjugant strain (chi3337/pR(ST98)). The
      bacterial strains incubated with J774A.1 revealed that survival rate of
      intracellular bacteria carrying pR(ST98) was higher than that of plasmid free
      strain; presence of pR(ST98) decreased the number of autophagy vacuoles, LC3
      positive and p62 positive bacteria, and also the level of LC3-II and degradation
      of p62 in macrophages. After intervention with autophagy inhibitor chloroquine,
      the amount of LC3-II and autophagy vacuoles were still lower in macrophages
      infected with strains carrying pR(ST98). Our study suggested that pR(ST98) could
      block or delay the formation of autophagosome in the earlier autophagy process,
      but couldn't affect the function of autolysosome. This finding provided novel
      insights into the role of enteric conjugation plasmid in bacterial pathogenesis.

PMID- 24857880
TI  - MicroRNA regulation of DNA repair gene expression in 4-aminobiphenyl-treated
      HepG2 cells.
AB  - We examined the role of miRNAs in DNA damage response in HepG2 cells following
      exposure to 4-aminobiphenyl (4-ABP). The arylamine 4-ABP is a human carcinogen.
      Using the Comet assay, we showed that 4-ABP (18.75-300MUM) induces DNA damage in
      HepG2 cells after 24h. DNA damage signaling pathway-based PCR arrays were used to
      investigate expression changes in genes involved in DNA damage response. Results
      showed down-regulation of 16 DNA repair-related genes in 4-ABP-treated cells.
      Among them, the expression of selected six genes (UNG, LIG1, EXO1, XRCC2, PCNA,
      and FANCG) from different DNA repair pathways was decreased with quantitative
      real-time PCR (qRT-PCR). In parallel, using the miRNA array, we reported that the
      expression of 27 miRNAs in 4-ABP-treated cells was at least 3-fold higher than
      that in the control group. Of these differential 27 miRNAs, the most significant
      expression of miRNA-513a-5p and miRNA-630 was further validated by qRT-PCR, and
      was predicted to be implicated in the deregulation of FANCG and RAD18 genes,
      respectively, via bioinformatic analysis. Both FANCG and RAD18 proteins were
      found to be down-regulated in 4-ABP-treated cells. In addition, overexpression
      and knockdown of miRNA-513a-5p and miRNA-630 reduced and increased the expression
      of FANCG and RAD18 proteins, respectively. Based on the above results, we
      indicated that miRNA-513a-5p and miRNA-630 could play a role in the suppression
      of DNA repair genes, and eventually lead to DNA damage. 

PMID- 24857881
TI  - F-order kinetics of photoreversible-drug reactions.
AB  - BACKGROUND: Drug photodegradation data are usually treated by zero-, first- or
      second-order kinetic equations. Such treatments would lack reliability since the
      aforementioned equations have been originally developed for pure thermal
      reactions. In this respect, it has recently been shown that unimolecular
      photodegradations obey F-order kinetics (Maafi and Maafi, 2013). However, no
      similar information is, thus far, available for other reactions including
      photoreversible AB(2F) systems. This paper aims at filling this gap for AB(2F)
      kinetics. METHODS: Runge-Kutta numerical integration data for photoreversible
      reactions traces were combined with a template equation in order to derive an
      optimized (semi-empirical) integrated rate-law equation for AB(2F) reactions. The
      proposed model equation was test by examining its ability to fit synthetic Runge
      Kutta data that have not been used for the optimization. The obtained fitting
      parameters are then compared to their theoretical counterparts. RESULTS: Both an
      integrated rate-law and an analytical equation for the overall reaction rate
      constant were set for photoreversible drug reactions. The values of overall
      reaction rate-constant and initial velocity obtained theoretically correlated
      well with those obtained by fitting the kinetic traces of reactions with the
      derived integrated rate-law. AB(2F) photodegradation reactions have been proven
      to obey F-order kinetics. The equation proposed describes faithfully their
      kinetic behaviour in solution. The formula of the overall rate-constant involves
      both reagents' characteristics and experimental parameters. These equations
      facilitated the rationalisation and prediction of the individual effects of each
      reaction parameter. Specially, our results proved a self-photostabilisation with
      increasing initial drug-concentration and demonstrated the potential for
      actinometry of drugs obeying AB(2F) mechanism.

PMID- 24857884
TI  - Do mantle cell lymphomas have an 'Achilles heel'?
AB  - PURPOSE OF REVIEW: Mantle cell lymphoma (MCL) is a mature B-cell malignancy that
      continues to have a high mortality rate. In this article, we discuss key
      pathogenic pathways in MCL biology and their possible therapeutic targeting.
      RECENT FINDINGS: In addition to cyclin-D1, the transcription factor SOX-11
      emerged as a common characteristic of MCL. Genomic studies have identified a
      number of recurrently mutated genes; in order of descending frequency these
      include ATM, CCND1, UBR5, TP53, BIRC3, NOTCH1/2 and TRAF2. However, no clear
      oncogenic driver has been identified. In contrast, several observations indicate
      that MCL cells are antigen-experienced cells and that the tumor microenvironment
      and B-cell receptor engagement are important. This is underscored by the
      impressive clinical responses achieved with the Bruton's tyrosine kinase
      inhibitor ibrutinib. Recently identified activating mutations in the noncanonical
      nuclear factor-kappa B pathway could give rise to ibrutinib resistance. Poly-ADP
      ribose polymerase and aurora kinase inhibitors may be synthetic lethal with the
      common aberrations in DNA damage pathways found in MCL. Also, ABT-199, a potent
      and selective inhibitor of B-cell lymphoma 2, has promising activity in early
      studies. SUMMARY: MCL is a heterogeneous disease, and no single Achilles heel has
      been identified. Nevertheless, genomic, molecular and clinical studies have
      revealed vulnerabilities that can be exploited for effective therapy.

PMID- 24857886
TI  - The clonal evolution of leukemic stem cells in T-cell acute lymphoblastic
      leukemia.
AB  - PURPOSE OF REVIEW: Recent genome sequencing studies have identified a broad
      spectrum of gene mutations in T-cell acute lymphoblastic leukemia (T-ALL). The
      purpose of this review is to outline the latest advances in our understanding of
      how these mutations contribute to the formation of T-ALL. RECENT FINDINGS:
      Aberrant expression of transcription factors that control hematopoiesis can
      induce an aberrant stem cell-like program in T-cell progenitors, allowing the
      emergence of an ancestral or preleukemic stem cell (pre-LSC). In contrast, gain
      of-function mutations of genes involved in signaling pathways regulating T-cell
      development, such as NOTCH1, interleukin-7, KIT and FLT3, are insufficient per se
      to initiate T-ALL but promote pre-LSC growth independent of the thymic niche.
      Loss-of-function mutations of epigenetic regulators, such as DNMT3A, have been
      identified in T-ALL, but their role in leukemogenesis remains to be defined.
      SUMMARY: Relapse is associated with clonal evolution from a population of pre
      LSCs that acquire the whole set of malignant mutations leading to a full-blown T
      ALL. Understanding the genetic events that underpin the pre-LSC will be crucial
      for reducing the risk of relapse.

PMID- 24857885
TI  - Kit and Scl regulation of hematopoietic stem cells.
AB  - PURPOSE OF REVIEW: KIT tyrosine kinase receptor is essential for several tissue
      stem cells, especially for hematopoietic stem cells (HSCs). Moderately decreased
      KIT signaling is well known to cause anemia and defective HSC self-renewal,
      whereas gain-of-function mutations are infrequently found in leukemias. Thus,
      maintaining KIT signal strength is critically important for homeostasis. KIT
      signaling in HSCs involves effectors such as SHP2 and PTPN11. This review
      summarizes the recent developments on the novel mechanisms regulating or
      reinforcing KIT signal strength in HSCs and its perturbation in polycythemia
      vera. RECENT FINDINGS: Stem cell leukemia (SCL) is a transcription factor that is
      essential for HSC development. Genetic experiments indicate that Kit, protein
      tyrosine phosphatase, nonreceptor type 11 (Ptpn11), or Scl control long-term HSC
      self-renewal, survival, and quiescence in adults. Kit is now shown to be
      centrally involved in two feedforward loops in HSCs, one with Ptpn11 and the
      other with Scl. SUMMARY: Knowledge of the regulatory mechanisms that favor self
      renewal divisions or a lineage determination process is central to the design of
      strategies to expand HSCs for the purpose of cell therapy. In addition,
      transcriptome and phosphoproteome analyses of erythroblasts in polycythemia vera
      identified lower SCL expression and hypophosphorylated KIT, suggesting that the
      KIT-SCL loop is relevant to the pathophysiology of human blood disorders as well.

PMID- 24857887
TI  - Escaping to the summits: phylogeography and predicted range dynamics of Cerastium
      dinaricum, an endangered high mountain plant endemic to the western Balkan
      Peninsula.
AB  - The Balkans are a major European biodiversity hotspot, however, almost nothing is
      known about processes of intraspecific diversification of the region's high
      altitude biota and their reaction to the predicted global warming. To fill this
      gap, genome size measurements, AFLP fingerprints, plastid and nuclear sequences
      were employed to explore the phylogeography of Cerastium dinaricum. Range size
      changes under future climatic conditions were predicted by niche-based modeling.
      Likely the most cold-adapted plant endemic to the Dinaric Mountains in the
      western Balkan Peninsula, the species has conservation priority in the European
      Union as its highly fragmented distribution range includes only few small
      populations. A deep phylogeographic split paralleled by divergent genome size
      separates the populations into two vicariant groups. Substructure is pronounced
      within the southeastern group, corresponding to the area's higher geographic
      complexity. Cerastium dinaricum likely responded to past climatic oscillations
      with altitudinal range shifts, which, coupled with high topographic complexity of
      the region and warmer climate in the Holocene, sculptured its present fragmented
      distribution. Field observations revealed that the species is rarer than
      previously assumed and, as shown by modeling, severely endangered by global
      warming as viable habitat was predicted to be reduced by more than 70% by the
      year 2080. 

PMID- 24857888
TI  - Branch density-controlled synthesis of hierarchical TiO2 nanobelt and tunable
      three-step electron transfer for enhanced photocatalytic property.
AB  - The successful adjustment of phase composition and morphology of hierarchical
      TiO2 nanobelts, which feature homoepitaxial nanobranches, has been developed via
      the hydrothermal method and chemical bath deposition technique. Effects of
      hydrothermal reaction time, titanium butoxide treatment in chemical bath
      deposition, and calcination temperature are systematically investigated. For the
      first time, three-step ultrafast electron transfers between the band edges of the
      engaged phases are realized through the enhanced photocatalytic activity results.
      Growth mechanism related to branch density control on nanobelt surface under such
      soft chemical process is discussed in detail on the basis of classical nucleation
      theory. The current work might provide new insights into the fabrication of one
      dimensional homoepitaxial branched TiO2 nanostructures as high performance
      photocatalysts and facilitate their application in environmental cleanup. 

PMID- 24857889
TI  - Chronic kidney disease, cardiovascular disease and mortality: A prospective
      cohort study in a multi-ethnic Asian population.
AB  - BACKGROUND: Few studies have examined the impact of chronic kidney disease (CKD)
      on adverse cardiovascular outcomes and deaths in Asian populations. We evaluated
      the associations of CKD with cardiovascular disease (CVD) and all-cause mortality
      in a multi-ethnic Asian population. DESIGN: Prospective cohort study of 7098
      individuals who participated in two independent population-based studies
      involving Malay adults (n = 3148) and a multi-ethnic cohort of Chinese, Malay and
      Indian adults (n = 3950). METHODS: CKD was assessed from CKD-EPI estimated
      glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR).
      Incident CVD (myocardial infarction, stroke and CVD mortality) and all-cause
      mortality were identified by linkage with national disease/death registries.
      RESULTS: Over a median follow-up of 4.3 years, 4.6% developed CVD and 6.1% died.
      Risks of both CVD and all-cause mortality increased with decreasing eGFR and
      increasing albuminuria (all p-trend <0.05). Adjusted hazard ratios (HR (95%
      confidence interval)) of CVD and all-cause mortality were: 1.54 (1.05-2.27) and
      2.21 (1.67-2.92) comparing eGFR <45 vs >=60; 2.81 (1.49-5.29) and 2.34 (1.28
      4.28) comparing UACR >=300 vs <30. The association between eGFR <60 and all-cause
      mortality was stronger among those with diabetes (p-interaction = 0.02). PAR of
      incident CVD was greater among those with UACR >=300 (12.9%) and that of all
      cause mortality greater among those with eGFR <45 (16.5%). CONCLUSIONS: In multi
      ethnic Asian adults, lower eGFR and higher albuminuria were independently
      associated with incident CVD and all-cause mortality. These findings extend
      previously reported similar associations in Western populations to Asians and
      emphasize the need for early detection of CKD and intervention to prevent adverse
      outcomes.

PMID- 24857890
TI  - Availability of, referral to and participation in exercise-based cardiac
      rehabilitation after heart valve surgery: Results from the national CopenHeart
      survey.
AB  - BACKGROUND: As with ischaemic heart disease, cardiac rehabilitation (CR) is
      recommended for patients undergoing heart valve surgery; recommendations are
      based on limited evidence. The organization of CR programmes and factors
      associated with uptake among patients undergoing heart valve surgery have not
      been studied. This study investigated CR programmes for these patients and
      factors associated with referral and participation. DESIGN AND METHODS: We
      distributed two nationwide surveys: one to 37 hospitals and 98 municipalities and
      one to 742 consecutive patients undergoing heart valve surgery. Data were linked
      to nationwide registries. We analysed the provision and content of programmes
      using descriptive statistics, and factors associated with referral and
      participation using logistic regression analysis. RESULTS: Coverage of CR
      programmes for these patients was high, with national programme variation. The
      overall uptake rate was 52%. Simultaneous CABG was associated with a higher
      probability of referral to CR (OR 2.02 (95%CI 1.12-3.65)); being unmarried (0.44
      (0.27-0.72)) and having TAVI with a lower probability (0.26; 0.13-0.52). The
      referral pattern varied across administrative regions, with patients in the
      capital region less likely to be referred (0.22 (0.08-0.57)). Patients with TAVI
      were less likely to participate (0.29 (0.12-0.70)). CONCLUSIONS: Despite high
      national programme coverage, only half the patients post heart valve surgery
      received CR. Both factors identified at provider- and patient-level influenced
      uptake and included significant regional variation in referral pattern. Further
      research into the effect and organization of CR post heart valve surgery is
      needed.

PMID- 24857892
TI  - An assessment of ozone levels, UV radiation and their occupational health hazard
      estimation during photocopying operation.
AB  - This study investigates the levels of ozone concentration along with an
      ultraviolet (UV) and visible spectral radiation at eight photocopy centers in an
      academic institute, Delhi. Sampling was done in two types of locations, i.e.,
      basement photocopy centers (BPC) and ground floor photocopy centers (GPC) for 8h.
      Measurements of levels of ozone, UV and visible radiation were done by ozone
      analyzer, UV radiometer and Field spectra instrument, respectively. Results show
      that the hourly mean concentration of ozone was observed to be in the range of
      1.8-10.0 ppb and 5.3-45.8 ppb for BPC and GPC, respectively. In terms UV
      radiations, energy lies between 5.0*10(-3) and 7.0*10(-3) mW/cm(2) for
      ultraviolet A (UVA), 1.0*10(-3) and 2.0*10(-3) mW/cm(2) for ultraviolet B (UVB)
      and 6.0*10(-3) and 8.0*10(-3) mW/cm(2) for ultraviolet C (UVC). Correlation
      between the UV radiations and ozone production observed was statistically
      insignificant. To know the health hazard occurred to the workers, the standard
      erythema dose (SED) value was calculated for emitting UV radiation. The SED was
      estimated to be in the range of 0.02-0.04 and 0.02-0.32 for direct and indirect
      methods which is less than the guideline prescribed by Commission Internationale
      del' Eclairage (CIE). In nutshell, person involved in photocopy operation for
      their livelihood must be trained and should have knowledge for the long term
      gradual build up health problems due to ozone and UV production from photocopier.
      The manufactures should be ultimated with the significant ozone production, so
      that photocopier machine can be redesigned.

PMID- 24857893
TI  - Metal accumulation and antioxidant defenses in the freshwater fish Carassius
      auratus in response to single and combined exposure to cadmium and hydroxylated
      multi-walled carbon nanotubes.
AB  - The effects of cadmium, hydroxylated multi-walled carbon nanotubes, and their
      mixture on metal accumulation and antioxidant defenses were studied using the
      goldfish Carassius auratus as the test organism. The fish were exposed to 0.1
      mg/L Cd, 0.5 mg/L OH-MWCNTs, or 0.1 mg/L Cd+0.5 mg/L OH-MWCNTs for 3 and 12 days.
      Then, the Cd concentration was determined in the gill, liver and muscle.
      Moreover, hepatic antioxidant enzyme activity (superoxide dismutase, catalase and
      glutathione peroxidase), glutathione level and malondialdehyde content were also
      measured. A continuous accumulation of Cd was observed throughout the
      experimental period. Cd accumulation in tissues occurred in the following order:
      gill>liver>muscle at 3 days and liver>gill>muscle at 12 days. The concentrations
      of Cd in the livers of fish exposed to the combination of Cd+OH-MWCNTs were
      significantly higher than those in fish exposed to either single chemical after
      12 d of exposure. Meanwhile, the mixture evoked severe oxidative stress in the
      exposed fish, as indicated by significant inhibition of SOD, CAT and GPx
      activity, a remarkable decrease in GSH level, and simultaneous elevation of MDA
      content. These results suggested that the effect of the combined factors on metal
      accumulation and oxidative stress biomarkers was more obvious than that of single
      factors at longer exposure durations.

PMID- 24857894
TI  - Enhancing trichloroethylene degradation using non-aromatic compounds as growth
      substrates.
AB  - The effect of non-aromatic compounds on the trichloroethylene (TCE) degradation
      of toluene-oxidizing bacteria were evaluated using Burkholderia cepacia G4 that
      expresses toluene 2-monooxygenase and Pseudomonas putida that expresses toluene
      dioxygenase. TCE degradation rates for B. cepacia G4 and P. putida with toluene
      alone as growth substrate were 0.144 and 0.123 MUg-TCE/mg-protein h,
      respectively. When glucose, acetate and ethanol were fed as additional growth
      substrates, those values increased up to 0.196, 0.418 and 0.530 MUg-TCE/mg
      protein h, respectively for B. cepacia G4 and 0.319, 0.219 and 0.373 MUg-TCE/mg
      protein h, respectively for P. putida. In particular, the addition of ethanol
      resulted in a high TCE degradation rate regardless of the initial concentration.
      The use of a non-aromatic compound as an additional substrate probably enhanced
      the TCE degradation because of the additional supply of NADH that is consumed in
      co-metabolic degradation of TCE. Also, it is expected that the addition of a non
      aromatic substrate can reduce the necessary dose of toluene and, subsequently,
      minimize the potential competitive inhibition upon TCE co-metabolism by toluene.

PMID- 24857895
TI  - Treatment of co-mingled benzene, toluene and TCE in groundwater.
AB  - This work addressed a hypothetical but practical scenario that includes
      biological oxidation and reductive dechlorination in treating groundwater
      containing co-mingled plume of trichloroethene (TCE), benzene and toluene.
      Groundwater immediately downgradient from the commonly used zero-valent iron
      (ZVI) has shown alkaline pH (up to 10.7). The elevated pH may influence BTEX
      compounds (i.e., benzene, toluene, ethyl benzene, and xylenes) biodegradation,
      which could also be inhibited by elevated concentrations of TCE. Data from this
      work suggests that the inhibition coefficients (IC) value for 100 MUg/L and 500
      MUg/L of TCE on benzene and toluene degradation are 2.1-2.8 at pH 7.9, and 3.5
      6.1 at pH 10.5. For a co-mingled plume, it appears to be more effective to reduce
      TCE by ZVI before addressing benzene and toluene biodegradation. The ample
      buffering capacity of most groundwater and the adaptation of benzene and toluene
      degrading microbes are likely able to eliminate the adverse influence of pH
      shifts downgradient from a ZVI-PRB.

PMID- 24857896
TI  - Review of iron-free Fenton-like systems for activating H2O2 in advanced oxidation
      processes.
AB  - Iron-catalyzed hydrogen peroxide decomposition for in situ generation of hydroxyl
      radicals (HO(*)) has been extensively developed as advanced oxidation processes
      (AOPs) for environmental applications. A variety of catalytic iron species
      constituting metal salts (in Fe(2+) or Fe(3+) form), metal oxides (e.g., Fe2O3,
      Fe3O4), and zero-valent metal (Fe(0)) have been exploited for chemical (classical
      Fenton), photochemical (photo-Fenton) and electrochemical (electro-Fenton)
      degradation pathways. However, the requirement of strict acidic conditions to
      prevent iron precipitation still remains the bottleneck for iron-based AOPs. In
      this article, we present a thorough review of alternative non-iron Fenton
      catalysts and their reactivity towards hydrogen peroxide activation. Elements
      with multiple redox states (like chromium, cerium, copper, cobalt, manganese and
      ruthenium) all directly decompose H2O2 into HO(*) through conventional Fenton
      like pathways. The in situ formation of H2O2 and decomposition into HO(*) can be
      also achieved using electron transfer mechanism in zero-valent aluminum/O2
      system. Although these Fenton systems (except aluminum) work efficiently even at
      neutral pH, the H2O2 activation mechanism is very specific to the nature of the
      catalyst and critically depends on its composition. This review describes in
      detail the complex mechanisms and emphasizes on practical limitations influencing
      their environmental applications. 

PMID- 24857897
TI  - Experimental design and optimization of leaching process for recovery of valuable
      chemical elements (U, La, V, Mo, Yb and Th) from low-grade uranium ore.
AB  - The paper deals with experimental design and optimization of leaching process of
      uranium and associated metals from low-grade, Polish ores. The chemical elements
      of interest for extraction from the ore were U, La, V, Mo, Yb and Th. Sulphuric
      acid has been used as leaching reagent. Based on the design of experiments the
      second-order regression models have been constructed to approximate the leaching
      efficiency of elements. The graphical illustrations using 3-D surface plots have
      been employed in order to identify the main, quadratic and interaction effects of
      the factors. The multi-objective optimization method based on desirability
      approach has been applied in this study. The optimum condition have been
      determined as P=5 bar, T=120  degrees C and t=90 min. Under these optimal
      conditions, the overall extraction performance is 81.43% (for U), 64.24% (for
      La), 98.38% (for V), 43.69% (for Yb) and 76.89% (for Mo) and 97.00% (for Th).

PMID- 24857898
TI  - Comparative evaluation of actinide ion uptake by polymer inclusion membranes
      containing TODGA as the carrier extractant.
AB  - Polymer inclusion membranes (PIM) containing TODGA (N,N,N',N'-tetra-n-octyl
      diglycolamide) were evaluated for the separation of actinide ions such as Am(3+),
      Pu(4+), UO2(2+) and Th(4+) from acidic feeds. The PIMs were prepared using
      cellulose triacetate (CTA) as the polymer matrix and 2-nitrophenyloctyl ether
      (NPOE) as the plasticizer along with the diglycolamide carrier extractants and
      were characterized by conventional techniques such as XRD, thermal analysis and
      AFM. The PIM composition was optimized by a series of studies which involved
      variation in the CTA, NPOE and carrier concentration which suggested 58% TODGA,
      30% NPOE and 12% CTA to be optimum. The uptake studies were carried out using
      feed solutions containing varying concentrations of nitric acid and showed the
      trend: Am(3+)>Pu(4+)>Th(4+)>UO2(2+). Transport studies were carried out in a two
      compartment cell where nitric acid concentration the feed was varied (1-3M) while
      the receiver compartment contained alpha-hydroxy-iso-butyric acid (AHIBA). The
      actinide ion transport efficiencies with TODGA containing PIMs followed the same
      trend as seen in the uptake studies. The AFM patterns of the PIMs changed when
      loaded with Eu(3+) carrier (used as a surrogate for Am(3+)) while the regenerated
      membranes have displayed comparable morphologies. Diffusion coefficient values
      were experimentally obtained from the transport studies and were found to be
      8.89*10(-8) cm(2)/s for Am(3+) transport.

PMID- 24857899
TI  - Analyses and decreasing patterns of veterinary antianxiety medications in soils.
AB  - An ultrasonic-assisted extraction method was developed to detect 16 antianxiety
      medications in soil samples using liquid chromatography-high resolution mass
      spectrometry (LC-HRMS), Orbitrap mass spectrometer. The determination method
      resulted in satisfactory sensitivity, linearity, recovery, repeatability, and
      within-laboratory reproducibility. Acepromazine, azaperone, and xylazine were
      incubated in control, amended, and sterilized soils. The amendment with powdered
      blood meal affected the relatively fast dissipations of acepromazine, azaperone,
      and xylazine in the soils. Dissipation kinetics of acepromazine were consistent
      with bi-phasic kinetics (first-order multi compartment) and the other couples
      were fit to single first-order kinetics. A hydroxylated acepromazine was
      identified from soil samples using Orbitrap mass spectrometry. According to
      sorption batch experiments, the adsorption of acepromazine and azaperone was
      greatly high, whereas that of xylazine was relatively low. Xylazine was
      persistent in the incubated soils, and acepromazine demonstrated fast initial
      dissipation; hence, xylazine could have a potential harmful effect on the
      environment. To the best of our knowledge, this is the first report on the
      dissipation and adsorption-desorption patters of animal pharmaceutical
      tranquilizers and alpha, beta-blockers. 

PMID- 24857900
TI  - Siloxanes removal from biogas by a lab-scale biotrickling filter inoculated with
      Pseudomonas aeruginosa S240.
AB  - Removing volatile methyl siloxanes (VMSs) from biogas remains a longstanding
      challenge in the field of biological process due to their low bioavailability and
      biodegradation. To address this issue, a lab-scale aerobic biotrickling filter,
      packed with porous lava and inoculated with an effective strain of Pseudomonas
      aeruginosa, was developed and its performance for octamethylcyclotetrasiloxane
      (D4, selected as a model VMS) removal from an aerobic synthetic gas was
      monitored. The biotrickling filter exhibited a relatively high removal efficiency
      over 74% at empty bed residence time of 13.2 min. Rhamnolipids, biosurfactants
      produced by P. aeruginosa, were identified in the liquid phase of the
      biotrickling filter by HPLC-MS and ATR-FTIR, and they were found to be the main
      factor of improving D4 removal. Moreover, dimethylsilanediol, methanol, silicic
      acid in the liquid phase and carbon dioxide in the gas phase, as the
      biodegradation products of D4, were determined by GC-MS, silicic acid analysis
      and non-dispersive infrared analysis. To our knowledge, it is the first time to
      report the existence of methanol in the D4 degradation products. Finally, a
      metabolic pathway for D4 degradation by P. aeruginosa was proposed based on our
      results.

PMID- 24857901
TI  - Efficient adsorption and photocatalytic degradation of Rhodamine B under visible
      light irradiation over BiOBr/montmorillonite composites.
AB  - BiOBr/Na-montmorillonite composites (BiOBr-Mt) were prepared under laboratory
      ambient conditions by using the surfactant cetyltrimethylammonium bromide (CTAB)
      as the Br source and template, and the as-synthesized samples were characterized
      by XRD, FT-IR, FESEM, TEM equipped with EDS, BET and UV-vis DRS techniques.
      Interestingly, the particle size of BiOBr can be controlled by CTAB modified Na
      montmorillonite. The photocatalytic activity of the as-prepared was further
      evaluated by decomposition of Rhodamine B (RhB) under visible light irradiation;
      the obtained results revealed that the BiOBr-Mt sample had strong photoabsorption
      in the visible light region. It has higher photocatalytic activity than pure
      BiOBr alone. There exists an efficient adsorption for RhB onto BiOBr-Mt contrast
      to that onto the pure BiOBr. The adsorption processes can be well described by
      pseudo-second-order kinetic model; meanwhile, the adsorption behaviors can be
      described by both Freundlich and Langmuir equations but the former was better.
      Additionally, the relevant adsorption and degradation mechanisms were explored
      and the possible mechanisms were presented. The photocatalytic activity has high
      effect both in acidic and basic conditions on the degradation reaction but in
      acidic condition is more favorable. After three recycles, BiOBr-Mt did not
      exhibit any significant loss of photocatalytic activity, confirming the
      photocatalyst was essentially stable. 

PMID- 24857902
TI  - Oxidative degradation of organic pollutants in aqueous solution using zero valent
      copper under aerobic atmosphere condition.
AB  - Oxidative degradation of organic pollutants and its mechanism were investigated
      in aqueous solution using zero valent copper (ZVC) under aerobic atmosphere
      condition. Diethyl phthalate (DEP) was completely oxidized after 120 min reaction
      by ZVC at initial pH 2.5 open to the air. DEP degradation followed the pseudo
      first-order kinetics after the lag period, and the degradation rate of DEP
      increased gradually with the increase of ZVC dosage, and the decrease of initial
      pH from 5.8 to 2.0. ZVC required a shorter induction time and exhibited
      persistent oxidation capacity compared to that of zero valent iron and zero
      valent aluminium. The mechanism investigation showed that remarkable amount of
      Cu(+)/Cu(2+) and H2O2 were formed in ZVC acidic system, which was due to the
      corrosive dissolution of ZVC and the concurrent reduction of oxygen. The addition
      of tert-butanol completely inhibited the degradation of DEP and the addition of
      Fe(2+) greatly enhanced the degradation rate, which demonstrated that hydroxyl
      radical was mainly responsible for the degradation of DEP in ZVC acidic system
      under aerobic atmosphere condition, and the formation of hydroxyl radical was
      attributed to the Fenton-like reaction of in situ formed Cu(+) with H2O2.

PMID- 24857903
TI  - Arsenite oxidation and removal driven by a bio-electro-Fenton process under
      neutral pH conditions.
AB  - The iron-catalyzed oxidation of arsenite (As(III)) associated with Fenton or
      Fenton-like reactions is one of the most efficient arsenic removal methods.
      However, the conventional chemical or electro-Fenton systems for the oxidation of
      As(III) are only efficient under acid conditions. In the present study, a cost
      effective and efficient bio-electro-Fenton process was performed for As(III)
      oxidation in a dual-chamber microbial fuel cell (MFC) under neutral pH
      conditions. In such a system, the Fenton reagents, including H2O2 and Fe(II),
      were generated in situ by microbial-driven electro-reduction of O2 and gamma
      FeOOH, respectively, without an electricity supply. The results indicated that
      the process was capable of inducing As(III) oxidation with an apparent As(III)
      depletion first-order rate constant of 0.208 h(-1). The apparent oxidation
      current efficiency was calculated to be as high as 73.1%. The gamma-FeOOH dosage
      in the cathode was an important factor in determining the system performance.
      Fourier-transform infrared spectroscopy (FT-IR) analysis indicated that As(V) was
      bound to the solid surface as a surface complex but not as a precipitated solid
      phase. The mechanism of bio-E-Fenton reaction for As(III) oxidation was also
      proposed. The bio-electro-Fenton system makes it potentially attractive method
      for the detoxification of As(III) from aqueous solution.

PMID- 24857904
TI  - Faster photodegradation rate and higher dioxin yield of triclosan induced by
      cationic surfactant CTAB.
AB  - Triclosan has received extensive attention as it has been frequently detected in
      the aquatic environment. Photolysis was found to be a major pathway governing the
      fate of triclosan in the aquatic environment. However, the effects of surfactants
      that usually coexist with triclosan, on the photodegradation of triclosan, are
      largely unknown. In this study, the effects of selected surfactants on the
      photodegradation of triclosan were investigated experimentally. The results show
      that anionic sodium dodecyl benzene sulfonate, sodium dodecyl sulfate and neutral
      polyoxyethylene (20) sorbitan monooleate inhibit the photolysis of triclosan,
      whereas cationic cetyltrimethylammonium bromide (CTAB) significantly accelerates
      the photodegradation rate of triclosan. The interactions between the hydrophilic
      group of CTAB and anionic triclosan lead to the apparent decrease of pKa of
      triclosan from 8.4 to 6.1, which increase the fraction of anionic triclosan from
      4% to 89% in neutral solution. A red shift in the UV-VIS absorption spectrum is
      exhibited, thus leading to the increased photodegradation rate of triclosan. The
      accelerations caused by CTAB were observed under xenon lamp and Hg lamp
      irradiances, as well as under natural sunlight. Effect of CTAB demonstrated pH
      dependence with significantly enhancement under pH 5~9 and inhibition at pH=3.
      The presence of CTAB also increased the yield of 2,8-dichlorodibenzo-p-dioxin
      from the photolysis of triclosan about 7 times at pH=7. 

PMID- 24857905
TI  - Correlation of near-infrared spectroscopy and direct pressure monitoring in an
      acute porcine compartmental syndrome model.
AB  - OBJECTIVE: To correlate near-infrared spectroscopy (NIRS) and the tibial
      intracompartmental perfusion pressure (TIPP) in an acute limb compartmental
      syndrome. METHODS: Landrace swine were subdivided into 2 groups: plasma infusion
      (n = 16) and blunt trauma plus plasma infusion (n = 15). NIRS sensors were placed
      over the craniolateral muscle compartment of proximal both tibiae. Albumin
      infusion elevated tibial intracompartmental pressures (TICP). Time-synchronized
      measures of systolic, diastolic, and mean arterial pressures, TICP, and percent
      oxygenation from each leg were collected. For the blunt trauma group, trauma was
      induced by dropping a 2-kg weight 30 times from 100 cm directly on the muscle
      compartment. For each group, a repeated-measures analysis of variance model was
      used to test differences in the TICP, TIPP, and oxygenation values. Pearson
      correlations were calculated between TICP and oxygenation and between TIPP and
      oxygenation. RESULTS: Both models created reproducible increases in TICP and
      decreases in TIPP. Trauma did not alter TICP, TIPP, or percent oxygenation in the
      model. NIRS was able to detect significant changes in tissue oxygenation at all
      the same time points. NIRS was able to detect decreased oxygenation at every TIPP
      decrease and subsequent increase after fasciotomies. An increase in percent
      oxygenation was seen in all cases once fasciotomy was performed and TICP was
      reduced. CONCLUSIONS: NIRS provided a sensitive measure correlating to both an
      increase and decrease in TICP and TIPP, respectively, in this infusion model. The
      addition of blunt trauma to the model did not alter the correlations of NIRS
      values with TICP and TIPP. Fasciotomy produced a rebound in oxygenation values.

PMID- 24857906
TI  - A modified posteromedial approach combined with extensile anterior for the
      treatment of complex tibial pilon fractures (AO/OTA 43-C).
AB  - The anterior approaches that have been described for open reduction internal
      fixation of multifragmentary pilon fractures are designed to reconstruct the
      comminuted and impacted anterior articular surface onto a stable posterior
      column. Thus, reduction of the posterior column, particularly proper length, is
      critical. There are differing opinions of how best to surgically approach the
      posterior pilon fracture. There is also no clear indication as to the timing of
      both anterior and posterior reconstructions. Our objectives were (1) to develop a
      more midline posterior approach that might provide better visualization of the
      posterior aspect of the posterior column and juxtametaphyseal/diaphyseal parts of
      the tibia, first on the cadaver and then with patients, and (2) to use this as
      part of a combined posterior and anterior approach during the same anesthesia for
      complex tibial pilon fractures (AO/OTA 43-C) in a preliminary study of 6
      patients.

PMID- 24857907
TI  - iHyd-PseAAC: predicting hydroxyproline and hydroxylysine in proteins by
      incorporating dipeptide position-specific propensity into pseudo amino acid
      composition.
AB  - Post-translational modifications (PTMs) play crucial roles in various cell
      functions and biological processes. Protein hydroxylation is one type of PTM that
      usually occurs at the sites of proline and lysine. Given an uncharacterized
      protein sequence, which site of its Pro (or Lys) can be hydroxylated and which
      site cannot? This is a challenging problem, not only for in-depth understanding
      of the hydroxylation mechanism, but also for drug development, because protein
      hydroxylation is closely relevant to major diseases, such as stomach and lung
      cancers. With the avalanche of protein sequences generated in the post-genomic
      age, it is highly desired to develop computational methods to address this
      problem. In view of this, a new predictor called "iHyd-PseAAC" (identify
      hydroxylation by pseudo amino acid composition) was proposed by incorporating the
      dipeptide position-specific propensity into the general form of pseudo amino acid
      composition. It was demonstrated by rigorous cross-validation tests on stringent
      benchmark datasets that the new predictor is quite promising and may become a
      useful high throughput tool in this area. A user-friendly web-server for iHyd
      PseAAC is accessible at http://app.aporc.org/iHyd-PseAAC/. Furthermore, for the
      convenience of the majority of experimental scientists, a step-by-step guide on
      how to use the web-server is given. Users can easily obtain their desired results
      by following these steps without the need of understanding the complicated
      mathematical equations presented in this paper just for its integrity. 

PMID- 24857908
TI  - Optimization of cell adhesion on mg based implant materials by pre-incubation
      under cell culture conditions.
AB  - Magnesium based implants could revolutionize applications where orthopedic
      implants such as nails, screws or bone plates are used because they are load
      bearing and degrade over time. This prevents a second surgery to remove
      conventional implants. To improve the biocompatibility we studied here if and for
      how long a pre-incubation of the material under cell culture conditions is
      favorable for cell attachment and proliferation. For two materials, Mg and
      Mg10Gd1Nd, we could show that 6 h pre-incubation are already enough to form a
      natural protective layer suitable for cell culture. 

PMID- 24857909
TI  - Molecular modelling study of the PPARgamma receptor in relation to the mode of
      action/adverse outcome pathway framework for liver steatosis.
AB  - The comprehensive understanding of the precise mode of action and/or adverse
      outcome pathway (MoA/AOP) of chemicals has become a key step toward the
      development of a new generation of predictive toxicology tools. One of the
      challenges of this process is to test the feasibility of the molecular modelling
      approaches to explore key molecular initiating events (MIE) within the integrated
      strategy of MoA/AOP characterisation. The description of MoAs leading to toxicity
      and liver damage has been the focus of much interest. Growing evidence underlines
      liver PPARgamma ligand-dependent activation as a key MIE in the elicitation of
      liver steatosis. Synthetic PPARgamma full agonists are of special concern, since
      they may trigger a number of adverse effects not observed with partial agonists.
      In this study, molecular modelling was performed based on the PPARgamma complexes
      with full agonists extracted from the Protein Data Bank. The receptor binding
      pocket was analysed, and the specific ligand-receptor interactions were
      identified for the most active ligands. A pharmacophore model was derived, and
      the most important pharmacophore features were outlined and characterised in
      relation to their specific role for PPARgamma activation. The results are useful
      for the characterisation of the chemical space of PPARgamma full agonists and
      could facilitate the development of preliminary filtering rules for the effective
      virtual ligand screening of compounds with PPARgamma full agonistic activity. 

PMID- 24857910
TI  - Huperzine A ameliorates cognitive deficits in streptozotocin-induced diabetic
      rats.
AB  - The present study was designed to probe the effects of Huperzine A (HupA) on
      diabetes-associated cognitive decline (DACD) using a streptozotocin (STZ)
      injected rat model. Diabetic rats were treated with HupA (0.05 and 0.1 mg/kg) for
      seven weeks. Memory functions were evaluated by the water maze test. Nissl
      staining was selected for detecting neuronal loss. Protein and mRNA levels of
      brain-derived neurotrophic factor (BDNF) were analyzed by ELISA and real-time
      PCR, respectively. The activities of choline acetylase (ChAT),
      Acetylcholinesterase (AChE), malondialdehyde (MDA), superoxide dismutase (SOD),
      glutathione peroxidase (GSH-Px), catalase (CAT), NF-kappaB p65 unit, TNF-alpha,
      IL-1beta, IL-6 and caspase-3 were measured using corresponding kits. After seven
      weeks, diabetic rats exhibited remarkable reductions in: body weight, percentage
      of time spent in target quadrant, number of times crossing the platform, ChAT and
      BDNF levels, SOD, GSH-Px and CAT accompanied with increases in neuronal damage,
      plasma glucose levels, escape latency, mean path length, AChE, MDA level as well
      as CAT, NF-kappaB p65 unit, TNF-alpha, IL-1beta, IL-6 and caspase-3 in cerebral
      cortex and hippocampus. Supplementation with HupA significantly and dose
      dependently reversed the corresponding values in diabetes. It is concluded that
      HupA ameliorates DACD via modulating BDNF, oxidative stress, inflammation and
      apoptosis. 

PMID- 24857911
TI  - Different role of tumor necrosis factor-alpha polymorphism in non-Hodgkin
      lymphomas among Caucasian and Asian populations: a meta-analysis.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is an immunoregulatory cytokine involved
      in B- and T-cell function, and also plays an important role in inflammation and
      cancer. TNF-alpha-308G>A has been associated with constitutively elevated TNF
      alpha expression. Several studies have reported the association between the TNF
      alpha-308G>A polymorphism and non-Hodgkin lymphomas (NHL) risk, however, results
      are still inconsistent. To solve these conflicts, we conducted the first meta
      analysis to assess the effect of TNF-alpha-308G>A polymorphism on the risk of NHL
      and various subtypes (additive model) including 10,619 cases and 12,977 controls
      in Caucasian and Asian populations. Our meta-analysis indicated that TNF-alpha
      308G>A polymorphism is not associated with NHL risk when pooling all studies
      together (OR=1.06, 95% CI: 0.92-1.23, p=0.413). In stratified analyses, we found
      TNF-alpha-308A allele was significantly associated with higher risk of NHL, B
      cell lymphomas (BCL), T-cell lymphomas (TCL) and diffuse large B-cell lymphomas
      (DLBCL) in Caucasians (OR=1.22, 95% CI: 1.06-1.40, p=0.007; OR=1.18, 95% CI: 1.03
      1.34, p=0.014; OR=1.20, 95% CI: 1.01-1.42, p=0.040; OR=1.21, 95% CI: 1.11-1.32,
      p<0.001, respectively). Interestingly, it was associated with decreased risk of
      NHL, BCL and DLBCL in Asians (OR=0.75, 95% CI: 0.66-0.86, p<0.001; OR=0.70, 95%
      CI: 0.52-0.94, p=0.018; OR=0.70, 95% CI: 0.57-0.86, p=0.001). These findings also
      suggest TNF-alpha might play a distinct role in pathogenesis of NHL in different
      populations.

PMID- 24857912
TI  - Development of a multiplex and cost-effective genotype test toward more
      personalized medicine for the antiplatelet drug clopidogrel.
AB  - There has been a wide range of inter-individual variations in platelet responses
      to clopidogrel. The variations in response to clopidogrel can be driven by
      genetic polymorphisms involved in the pathway of absorption, distribution,
      metabolism, excretion, and the target receptor P2Y12. A set of genetic variants
      known for causing variations in clopidogrel responses was selected, which
      included CYP2C19*2, *3, *17, CYP2B6*4, *6, *9, CYP3A4*18, CYP3A5*3, MDR1
      2677G>T/A, 3435C>T, and P2Y12 H2 (742T>C). The simultaneous detection of these 10
      variants was developed by using a multiplex PCR and single-base extension (MSSE)
      methodology. The newly developed genotyping test was confirmed by direct DNA
      sequencing in the representative positive control samples and validated in an
      extended set of 100 healthy Korean subjects. Genotyping results from the
      developed MSSE exhibited a perfect concordance with the direct DNA sequencing
      data and all of variants tested in 100 healthy Korean subjects were in agreement
      with Hardy-Weinberg equilibrium (p>0.05). The present molecular diagnostic
      studies provide an accurate, convenient, and fast genotyping method for the
      detection of multiple variants. This would be helpful for researchers, as well as
      clinicians, to use genetic information toward more personalized medicine of
      clopidogrel and other antiplatelet drugs in the future.

PMID- 24857913
TI  - Enamel matrix derivative promote primary human pulp cell differentiation and
      mineralization.
AB  - Enamel matrix derivative (EMD) has been found to induce reactive dentin
      formation; however the molecular mechanisms involved are unclear. The effect of
      EMD (5-50 MUg/mL) on primary human pulp cells were compared to untreated cells
      and cells incubated with 10-8 M dexamethasone (DEX) for 1, 2, 3, 7, and 14 days
      in culture. Expression analysis using Affymetrix microchips demonstrated that 10
      MUg/mL EMD regulated several hundred genes and stimulated the gene expression of
      proteins involved in mesenchymal proliferation and differentiation. Both EMD and
      DEX enhanced the expression of amelogenin (amel), and the dentinogenic markers
      dentin sialophosphoprotein (DSSP) and dentin matrix acidic phosphoprotein 1
      (DMP1), as well as the osteogenic markers osteocalcin (OC, BGLAP) and collagen
      type 1 (COL1A1). Whereas, only EMD had effect on alkaline phosphatase (ALP) mRNA
      expression, the stimulatory effect were verified by enhanced secretion of OC and
      COL1A from EMD treated cells, and increased ALP activity in cell culture medium
      after EMD treatment. Increased levels of interleukin-6 (IL-6), interleukin-8 (IL
      8), and monocyte chemoattractant proteins (MCP-1) in the cell culture medium were
      also found. Consequently, the suggested effect of EMD is to promote
      differentiation of pulp cells and increases the potential for pulpal
      mineralization to favor reactive dentine formation.

PMID- 24857914
TI  - Synthesis, preliminary bioevaluation and computational analysis of caffeic acid
      analogues.
AB  - A series of caffeic acid amides were designed, synthesized and evaluated for anti
      inflammatory activity. Most of them exhibited promising anti-inflammatory
      activity against nitric oxide (NO) generation in murine macrophage RAW264.7
      cells. A 3D pharmacophore model was created based on the biological results for
      further structural optimization. Moreover, predication of the potential targets
      was also carried out by the PharmMapper server. These amide analogues represent a
      promising class of anti-inflammatory scaffold for further exploration and target
      identification. 

PMID- 24857915
TI  - Molecular characterization of alpha- and beta-thalassaemia among Malay patients.
AB  - Both alpha- and beta-thalassaemia syndromes are public health problems in the
      multi-ethnic population of Malaysia. To molecularly characterise the alpha- and
      beta-thalassaemia deletions and mutations among Malays from Penang, Gap-PCR and
      multiplexed amplification refractory mutation systems were used to study 13 alpha
      thalassaemia determinants and 20 beta-thalassaemia mutations in 28 and 40
      unrelated Malays, respectively. Four alpha-thalassaemia deletions and mutations
      were demonstrated. --SEA deletion and alphaCSalpha accounted for more than 70% of
      the alpha-thalassaemia alleles. Out of the 20 beta-thalassaemia alleles studied,
      nine different beta-thalassaemia mutations were identified of which betaE
      accounted for more than 40%. We concluded that the highest prevalence of (alpha-
      and beta-thalassaemia alleles in the Malays from Penang are --SEA deletion and
      betaE mutation, respectively. 

PMID- 24857916
TI  - Selection of suitable endogenous reference genes for relative copy number
      detection in sugarcane.
AB  - Transgene copy number has a great impact on the expression level and stability of
      exogenous gene in transgenic plants. Proper selection of endogenous reference
      genes is necessary for detection of genetic components in genetically
      modification (GM) crops by quantitative real-time PCR (qPCR) or by qualitative
      PCR approach, especially in sugarcane with polyploid and aneuploid genomic
      structure. qPCR technique has been widely accepted as an accurate, time-saving
      method on determination of copy numbers in transgenic plants and on detection of
      genetically modified plants to meet the regulatory and legislative requirement.
      In this study, to find a suitable endogenous reference gene and its real-time PCR
      assay for sugarcane (Saccharum spp. hybrids) DNA content quantification, we
      evaluated a set of potential "single copy" genes including P4H, APRT, ENOL, CYC,
      TST and PRR, through qualitative PCR and absolute quantitative PCR. Based on copy
      number comparisons among different sugarcane genotypes, including five S.
      officinarum, one S. spontaneum and two S. spp. hybrids, these endogenous genes
      fell into three groups: ENOL-3--high copy number group, TST-1 and PRR-1--medium
      copy number group, P4H-1, APRT-2 and CYC-2--low copy number group. Among these
      tested genes, P4H, APRT and CYC were the most stable, while ENOL and TST were the
      least stable across different sugarcane genotypes. Therefore, three primer pairs
      of P4H-3, APRT-2 and CYC-2 were then selected as the suitable reference gene
      primer pairs for sugarcane. The test of multi-target reference genes revealed
      that the APRT gene was a specific amplicon, suggesting this gene is the most
      suitable to be used as an endogenous reference target for sugarcane DNA content
      quantification. These results should be helpful for establishing accurate and
      reliable qualitative and quantitative PCR analysis of GM sugarcane.

PMID- 24857917
TI  - The cytoprotective effect of sulfuretin against tert-butyl hydroperoxide-induced
      hepatotoxicity through Nrf2/ARE and JNK/ERK MAPK-mediated heme oxygenase-1
      expression.
AB  - Sulfuretin is one of the major flavonoid components in Rhus verniciflua Stokes
      (Anacardiaceae) isolates. In this study, we investigated the protective effects
      of sulfuretin against tert-butyl hydroperoxide (t-BHP)-induced oxidative injury.
      The results indicated that the addition of sulfuretin before t-BHP treatment
      significantly inhibited cytotoxicity and reactive oxygen species (ROS) production
      in human liver-derived HepG2 cells. Sulfuretin up-regulated the activity of the
      antioxidant enzyme heme oxygenase (HO)-1 via nuclear factor E2-related factor 2
      (Nrf2) translocation into the nucleus and increased the promoter activity of the
      antioxidant response element (ARE). Moreover, sulfuretin exposure enhanced the
      phosphorylation of c-Jun N-terminal kinase (JNK) and extracellular signal
      regulated kinase 1/2 (ERK1/2), which are members of the mitogen-activated protein
      kinase (MAPK) family. Furthermore, cell treatment with a JNK inhibitor (SP600125)
      and ERK inhibitor (PD98059) reduced sulfuretin-induced HO-1 expression and
      decreased its protective effects. Taken together, these results suggest that the
      protective effect of sulfuretin against t-BHP-induced oxidative damage in human
      liver-derived HepG2 cells is attributable to its ability to scavenge ROS and up
      regulate the activity of HO-1 through the Nrf2/ARE and JNK/ERK signaling
      pathways. Therefore, sulfuretin could be advantageous as a bioactive source for
      the prevention of oxidative injury. 

PMID- 24857918
TI  - Marine microbial metagenomics: from individual to the environment.
AB  - Microbes are the most abundant biological entities on earth, therefore, studying
      them is important for understanding their roles in global ecology. The science of
      metagenomics is a relatively young field of research that has enjoyed significant
      effort since its inception in 1998. Studies using next-generation sequencing
      techniques on single genomes and collections of genomes have not only led to
      novel insights into microbial genomics, but also revealed a close association
      between environmental niches and genome evolution. Herein, we review studies
      investigating microbial genomics (largely in the marine ecosystem) at the
      individual and community levels to summarize our current understanding of
      microbial ecology in the environment. 

PMID- 24857920
TI  - Chemical characterization and antitumor activities of polysaccharide extracted
      from Ganoderma lucidum.
AB  - Ganoderma lucidum polysaccharide (GLP) is a biologically active substance
      reported to possess anti-tumor ability. Nonetheless, the mechanisms of GLP
      stimulated apoptosis are still unclear. This study aims to determine the
      inhibitory and apoptosis-inducing effects of GLP on HCT-116 cells. We found that
      GLP reduced cell viability on HCT-116 cells in a time- and dose-dependent manner,
      which in turn, induced cell apoptosis. The observed apoptosis was characterized
      by morphological changes, DNA fragmentation, mitochondrial membrane potential
      decrease, S phase population increase, and caspase-3 and -9 activation.
      Furthermore, inhibition of c-Jun N-terminal kinase (JNK) by SP600125 led to a
      dramatic decrease of the GLP-induced apoptosis. Western blot analysis unveiled
      that GLP up-regulated the expression of Bax/Bcl-2, caspase-3 and poly (ADP
      ribose) polymerase (PARP). These results demonstrate that apoptosis stimulated by
      GLP in human colorectal cancer cells is associated with activation of
      mitochondrial and mitogen-activated protein kinase (MAPK) pathways. 

PMID- 24857921
TI  - Brain metastasis-initiating cells: survival of the fittest.
AB  - Brain metastases (BMs) are the most common brain tumor in adults, developing in
      about 10% of adult cancer patients. It is not the incidence of BM that is
      alarming, but the poor patient prognosis. Even with aggressive treatments, median
      patient survival is only months. Despite the high rate of BM-associated
      mortality, very little research is conducted in this area. Lack of research and
      staggeringly low patient survival is indicative that a novel approach to BMs and
      their treatment is needed. The ability of a small subset of primary tumor cells
      to produce macrometastases is reminiscent of brain tumor-initiating cells (BTICs)
      or cancer stem cells (CSCs) hypothesized to form primary brain tumors. BTICs are
      considered stem cell-like due to their self-renewal and differentiation
      properties. Similar to the subset of cells forming metastases, BTICs are most
      often a rare subpopulation. Based on the functional definition of a TIC, cells
      capable of forming a BM could be considered to be brain metastasis-initiating
      cells (BMICs). These putative BMICs would not only have the ability to initiate
      tumor growth in a secondary niche, but also the machinery to escape the primary
      tumor, migrate through the circulation, and invade the neural niche. 

PMID- 24857922
TI  - Aerobic degradation of trichloroethylene by co-metabolism using phenol and
      gasoline as growth substrates.
AB  - Trichloroethylene (TCE) is a common groundwater contaminant of toxic and
      carcinogenic concern. Aerobic co-metabolic processes are the predominant pathways
      for TCE complete degradation. In this study, Pseudomonas fluorescens was studied
      as the active microorganism to degrade TCE under aerobic condition by co
      metabolic degradation using phenol and gasoline as growth substrates. Operating
      conditions influencing TCE degradation efficiency were optimized. TCE co
      metabolic degradation rate reached the maximum of 80% under the optimized
      conditions of degradation time of 3 days, initial OD600 of microorganism culture
      of 0.14 (1.26*107 cell/mL), initial phenol concentration of 100 mg/L, initial TCE
      concentration of 0.1 mg/L, pH of 6.0, and salinity of 0.1%. The modified
      transformation capacity and transformation yield were 20 MUg (TCE)/mg (biomass)
      and 5.1 MUg (TCE)/mg (phenol), respectively. Addition of nutrient broth promoted
      TCE degradation with phenol as growth substrate. It was revealed that catechol
      1,2-dioxygenase played an important role in TCE co-metabolism. The dechlorination
      of TCE was complete, and less chlorinated products were not detected at the end
      of the experiment. TCE could also be co-metabolized in the presence of gasoline;
      however, the degradation rate was not high (28%). When phenol was introduced into
      the system of TCE and gasoline, TCE and gasoline could be removed at substantial
      rates (up to 59% and 69%, respectively). This study provides a promising approach
      for the removal of combined pollution of TCE and gasoline.

PMID- 24857919
TI  - Cancer stem cell theory and the warburg effect, two sides of the same coin?
AB  - Over the last 100 years, many studies have been performed to determine the
      biochemical and histopathological phenomena that mark the origin of neoplasms. At
      the end of the last century, the leading paradigm, which is currently well
      rooted, considered the origin of neoplasms to be a set of genetic and/or
      epigenetic mutations, stochastic and independent in a single cell, or rather, a
      stochastic monoclonal pattern. However, in the last 20 years, two important areas
      of research have underlined numerous limitations and incongruities of this
      pattern, the hypothesis of the so-called cancer stem cell theory and a
      revaluation of several alterations in metabolic networks that are typical of the
      neoplastic cell, the so-called Warburg effect. Even if this specific "metabolic
      sign" has been known for more than 85 years, only in the last few years has it
      been given more attention; therefore, the so-called Warburg hypothesis has been
      used in multiple and independent surveys. Based on an accurate analysis of a
      series of considerations and of biophysical thermodynamic events in the
      literature, we will demonstrate a homogeneous pattern of the cancer stem cell
      theory, of the Warburg hypothesis and of the stochastic monoclonal pattern; this
      pattern could contribute considerably as the first basis of the development of a
      new uniform theory on the origin of neoplasms. Thus, a new possible
      epistemological paradigm is represented; this paradigm considers the Warburg
      effect as a specific "metabolic sign" reflecting the stem origin of the
      neoplastic cell, where, in this specific metabolic order, an essential reason for
      the genetic instability that is intrinsic to the neoplastic cell is defined. 

PMID- 24857923
TI  - Functional polymorphisms of the ABCG2 gene are associated with gout disease in
      the Chinese Han male population.
AB  - BACKGROUND: Gout is a common type of arthritis that is characterized by
      hyperuricemia, tophi and joint inflammation. Genetic variations in the ABCG2 gene
      have been reported to influence serum uric acid levels and to participate in the
      pathogenesis of gout, but no further data have been reported in the Han Chinese
      population. METHODS: Peripheral blood DNA was isolated from 352 male patients
      with gout and 350 gout-free normal male controls. High-resolution melting
      analysis and Sanger sequencing were performed to identify the genetic
      polymorphisms V12M, Q141K and Q126X in the ABCG2 gene. Genotype and haplotype
      analyses were utilized to determine the disease odds ratios (ORs). A prediction
      model for gout risk using ABCG2 protein function was established based on the
      genotype combination of Q126X and Q141K. RESULTS: For Q141K, the A allele
      frequency was 49.6% in the gout patients and 30.9% in the controls (OR 2.20, 95%
      confidence interval (CI): 1.77-2.74, p=8.99*10-13). Regarding Q126X, the T allele
      frequency was 4.7% in the gout patients and 1.7% in the controls (OR 2.91, 95%
      CI: 1.49-5.68, p=1.57*10-3). The A allele frequency for V12M was lower (18.3%) in
      the gout patients than in the controls (29%) (OR 0.55, 95% CI 0.43-0.71,
      p=2.55*10-6). In the order of V12M, Q126X and Q141K, the GCA and GTC haplotypes
      indicated increased disease risk (OR=2.30 and 2.71, respectively). Patients with
      mild to severe ABCG2 dysfunction accounted for 78.4% of gout cases. CONCLUSION:
      The ABCG2 126X and 141K alleles are associated with an increased risk of gout,
      whereas 12M has a protective effect on gout susceptibility in the Han Chinese
      population. ABCG2 dysfunction can be used to evaluate gout risk.

PMID- 24857925
TI  - Dynamic formation of macular microcysts independent of vitreous traction changes.
AB  - OBJECTIVE: To test the assumption of vitreous traction as a cause of macular
      microcysts in neuroinflammatory diseases and to establish a testable model to
      quantify vitreous traction changes. METHODS: Retrospective cohort study including
      9 patients with neuroinflammatory diseases and macular microcysts that were
      longitudinally analyzed using optical coherence tomography. A mechanical model
      was developed to test the theory of vitreous traction vs macular swelling. This
      model was applied to one case presenting with dynamic microcyst evolution over 2
      years with 4 visits. RESULTS: None of the patients' eyes with microcysts showed
      any signs of vitreous traction upon qualitative meticulous optical coherence
      tomographic analysis. The longitudinal changes analyzed in one patient were in
      the opposite direction as predicted by the mechanical model involving vitreous
      traction. CONCLUSIONS: Vitreous traction does not appear to be a causative factor
      in macular microcyst formation. Quantitative analysis in one case shows even a
      reduced traction caused by an increase in macular thickness leading to vitreous
      impingement by the macular wall. The presented model might also serve as a
      quantification approach in other studies investigating macular microcysts.

PMID- 24857924
TI  - The peroxisome proliferator-activated receptor (PPAR) alpha agonist fenofibrate
      suppresses chemically induced lung alveolar proliferative lesions in male obese
      hyperlipidemic mice.
AB  - Activation of peroxisome proliferator-activated receptor (PPAR) alpha disrupts
      growth-related activities in a variety of human cancers. This study was designed
      to determine whether fenofibrate, a PPARalpha agonist, can suppress 4
      nitroquinoline 1-oxide (4-NQO)-induced proliferative lesions in the lung of obese
      hyperlipidemic mice. Male Tsumura Suzuki Obese Diabetic mice were subcutaneously
      injected with 4-NQO to induce lung proliferative lesions, including
      adenocarcinomas. They were then fed a diet containing 0.01% or 0.05% fenofibrate
      for 29 weeks, starting 1 week after 4-NQO administration. At week 30, the
      incidence and multiplicity (number of lesions/mouse) of pulmonary proliferative
      lesions were lower in mice treated with 4-NQO and both doses of fenofibrate
      compared with those in mice treated with 4-NQO alone. The incidence and
      multiplicity of lesions were significantly lower in mice treated with 4-NQO and
      0.05% fenofibrate compared with those in mice treated with 4-NQO alone (p<0.05).
      Both doses of fenofibrate significantly reduced the proliferative activity of the
      lesions in 4-NQO-treated mice (p<0.05). Fenofibrate also significantly reduced
      the serum insulin and insulin-like growth factor (IGF)-1 levels, and decreased
      the immunohistochemical expression of IGF-1 receptor (IGF-1R), phosphorylated
      Akt, and phosphorylated Erk1/2 in lung adenocarcinomas. Our results indicate that
      fenofibrate can prevent the development of 4-NQO-induced proliferative lesions in
      the lung by modulating the insulin-IGF axis.

PMID- 24857926
TI  - Spectrogram screening of adult EEGs is sensitive and efficient.
AB  - OBJECTIVE: Quantitatively evaluate whether screening with compressed spectral
      arrays (CSAs) is a practical and time-effective protocol for assisting expert
      review of continuous EEG (cEEG) studies in hospitalized adults. METHODS: Three
      neurophysiologists reviewed the reported findings of the first 30 minutes of 118
      cEEGs, then used CSA to guide subsequent review ("CSA-guided review" protocol).
      Reviewers viewed 120 seconds of raw EEG data surrounding suspicious CSA segments.
      The same neurophysiologists performed independent page-by-page visual
      interpretation ("conventional review") of all cEEGs. Independent conventional
      review by 2 additional, more experienced neurophysiologists served as a gold
      standard. We compared review times and detection rates for seizures and other
      pathologic patterns relative to conventional review. RESULTS: A total of 2,092
      hours of cEEG data were reviewed. Average times to review 24 hours of cEEG data
      were 8 (+/-4) minutes for CSA-guided review vs 38 (+/-17) minutes for
      conventional review (p < 0.005). Studies containing seizures required longer
      review: 10 (+/-4) minutes for CSA-guided review vs 44 (+/-20) minutes for
      conventional review (p < 0.005). CSA-guided review was sensitive for seizures
      (87.3%), periodic epileptiform discharges (100%), rhythmic delta activity
      (97.1%), focal slowing (98.7%), generalized slowing (100%), and epileptiform
      discharges (88.5%). CONCLUSIONS: CSA-guided review reduces cEEG review time by
      78% with minimal loss of sensitivity compared with conventional review.
      CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that screening
      of cEEG with CSAs efficiently and accurately identifies seizures and other EEG
      abnormalities as compared with standard cEEG visual interpretation.

PMID- 24857927
TI  - Inclusion body myositis and chronic lymphocytic leukemia: a case series.

PMID- 24857928
TI  - Manipulating the epigenome in germinal center lymphomas: is it getting easier and
      ezier?
AB  - Mutations affecting key epigenetic modifiers tend to cluster in malignancies in
      which cells of origin lie in the germinal center (GC). EZH2, as transcriptional
      repressor, is mutated in high frequency in Chinese and Western patients with
      follicular lymphoma and may represent a rational target for GC-derived lymphomas.
      .

PMID- 24857929
TI  - Mapping chemical elements on the surface of orthodontic appliance by SEM-EDX.
AB  - BACKGROUND: During orthodontic treatment, the various elements that constitute
      the fixed appliance undergo different processes. As a result of a change of the
      surface, elution/coverage of metals on the surface can be observed in the process
      of corrosion/passivation. MATERIAL AND METHODS: Scanning electron microscopy with
      an energy-dispersive X-ray analytical system (SEM-EDX) was used to analyze the
      composition of stainless steel elements of orthodontic fixed appliances (before
      and after orthodontic treatment), to obtain the composition of the surface of the
      elements. The analyzed elements were: brackets (Victory Series APC PLUS 022, 3M
      Unitek, Monrovia, CA, USA); wires (0.017*0.025, 3M Unitek, Monrovia, CA, USA);
      and bands (37+, 3M Unitek, Monrovia, CA, USA). RESULTS: The results showed a
      decrease of chromium and iron contribution to the surface, with increase of
      oxygen content in used vs. new elements of the appliance. CONCLUSIONS: Our
      results confirm the formation of oxides (passivation layer) on the surface of
      stainless steel as a result of the presence of the orthodontic appliance in
      patients' oral cavities.

PMID- 24857931
TI  - The Challenges of Providing Culturally Competent Care Within a Disability Focused
      Team: A Phenomenological Exploration of Staff Experiences.
AB  - PURPOSE: The study explored how service providers address the challenges of
      providing culturally competent care within disability services in the United
      Kingdom. DESIGN/METHOD: Focus groups and interpretative phenomenological analysis
      were used to explore the experiences of 20 service providers from a range of
      professions, working with South Asian families. RESULTS/FINDINGS: Two
      superordinate themes emerged. The first concentrated on difficulties with
      language and communication and the challenges posed by the use of interpreters.
      The second included five subthemes that broadly described a five-stage process of
      dealing with barriers and engagement to service delivery, followed by reflections
      on the effort made to provide culturally competent care in the face of limited
      resources and training. DISCUSSION/CONCLUSION: The study makes recommendations
      for cultural competency within health and social care services.

PMID- 24857932
TI  - Intrathecal infusion of hydrogen-rich normal saline attenuates neuropathic pain
      via inhibition of activation of spinal astrocytes and microglia in rats.
AB  - BACKGROUND: Reactive oxygen and nitrogen species are key molecules that mediate
      neuropathic pain. Although hydrogen is an established antioxidant, its effect on
      chronic pain has not been characterized. This study was to investigate the
      efficacy and mechanisms of hydrogen-rich normal saline induced analgesia.
      METHODOLOGY/PRINCIPAL FINDINGS: In a rat model of neuropathic pain induced by L5
      spinal nerve ligation (L5 SNL), intrathecal injection of hydrogen-rich normal
      saline relieved L5 SNL-induced mechanical allodynia and thermal hyperalgesia.
      Importantly, repeated administration of hydrogen-rich normal saline did not lead
      to tolerance. Preemptive treatment with hydrogen-rich normal saline prevented
      development of neuropathic pain behavior. Immunofluorochrome analysis revealed
      that hydrogen-rich normal saline treatment significantly attenuated L5 SNL
      induced increase of 8-hydroxyguanosine immunoreactive cells in the ipsilateral
      spinal dorsal horn. Western blot analysis of SDS/PAGE-fractionated tyrosine
      nitrated proteins showed that L5 SNL led to increased expression of tyrosine
      nitrated Mn-containing superoxide dismutase (MnSOD) in the spinal cord, and
      hydrogen-rich normal saline administration reversed the tyrosine-nitrated MnSOD
      overexpression. We also showed that the analgesic effect of hydrogen-rich normal
      saline was associated with decreased activation of astrocytes and microglia,
      attenuated expression of interleukin-1beta (IL-1beta) and tumor necrosis factor
      alpha (TNF-alpha) in the spinal cord. CONCLUSION/SIGNIFICANCE: Intrathecal
      injection of hydrogen-rich normal saline produced analgesic effect in neuropathic
      rat. Hydrogen-rich normal saline-induced analgesia in neuropathic rats is
      mediated by reducing the activation of spinal astrocytes and microglia, which is
      induced by overproduction of hydroxyl and peroxynitrite.

PMID- 24857933
TI  - Atomic force microscopy reveals a role for endothelial cell ICAM-1 expression in
      bladder cancer cell adherence.
AB  - Cancer metastasis is a complex process involving cell-cell interactions mediated
      by cell adhesive molecules. In this study we determine the adhesion strength
      between an endothelial cell monolayer and tumor cells of different metastatic
      potentials using Atomic Force Microscopy. We show that the rupture forces of
      receptor-ligand bonds increase with retraction speed and range between 20 and 70
      pN. It is shown that the most invasive cell lines (T24, J82) form the strongest
      bonds with endothelial cells. Using ICAM-1 coated substrates and a monoclonal
      antibody specific for ICAM-1, we demonstrate that ICAM-1 serves as a key receptor
      on endothelial cells and that its interactions with ligands expressed by tumor
      cells are correlated with the rupture forces obtained with the most invasive
      cancer cells (T24, J82). For the less invasive cancer cells (RT112), endothelial
      ICAM-1 does not seem to play any role in the adhesion process. Moreover, a
      detailed analysis of the distribution of rupture forces suggests that ICAM-1
      interacts preferentially with one ligand on T24 cancer cells and with two ligands
      on J82 cancer cells. Possible counter receptors for these interactions are CD43
      and MUC1, two known ligands for ICAM-1 which are expressed by these cancer cells.

PMID- 24857934
TI  - Coping with asymmetry: how infants and adults walk with one elongated leg.
AB  - The stability of a system affects how it will handle a perturbation: The system
      may compensate for the perturbation or not. This study examined how 14-month-old
      infants-notoriously unstable walkers-and adults cope with a perturbation to
      walking. We attached a platform to one of participants' shoes, forcing them to
      walk with one elongated leg. At first, the platform shoe caused both age groups
      to slow down and limp, and caused infants to misstep and fall. But after a few
      trials, infants altered their gait to compensate for the platform shoe whereas
      adults did not; infants recovered symmetrical gait whereas adults continued to
      limp. Apparently, adult walking was stable enough to cope with the perturbation,
      but infants risked falling if they did not compensate. Compensation depends on
      the interplay of multiple factors: The availability of a compensatory response,
      the cost of compensation, and the stability of the system being perturbed. 

PMID- 24857935
TI  - Daptomycin forms cation- and size-selective pores in model membranes.
AB  - Daptomycin is a lipopeptide antibiotic that is used clinically to treat severe
      infections caused by Gram-positive bacteria. Its bactericidal action involves the
      calcium-dependent binding to membranes containing phosphatidylglycerol, followed
      by the formation of membrane-associated oligomers. Bacterial cells exposed to
      daptomycin undergo membrane depolarization, suggesting the formation of channels
      or pores in the target membranes. We here used a liposome model to detect and
      characterize the permeability properties of the daptomycin pores. The pores are
      selective for cations, with permeabilities being highest for Na(+), K(+), and
      other alkali metal ions. The permeability is approximately twice lower for
      Mg(++), and lower again for the organic cations choline and hexamethonium. Anions
      are excluded, as is the zwitterion cysteine. These observations account for the
      observed depolarization of bacterial cells by daptomycin and suggest that under
      typical in vivo conditions depolarization is mainly due to sodium influx. 

PMID- 24857936
TI  - Inadvertent subclavian artery cannulation and options for management.
AB  - Central line placement is an integral part of our daily routine and although it
      is necessary in a select group of patients, serious complications may occur in up
      to 10% of cases. Inadvertent placement in the subclavian artery is considered to
      be one of the most challenging complications to the vascular specialist, which is
      mainly due to its deep anatomical location. Several endovascular options are
      available and should be tailored to fit each scenario. Herein, we present
      different approaches for the management of three cases of inadvertent subclavian
      artery cannulation. The first patient was treated with a covered stent, the
      second with prolonged balloon inflation, and the third with a closure device. 

PMID- 24857937
TI  - Construction and validation of a novel dual reporter vector for studying
      mammalian bidirectional promoters.
AB  - Regulation of gene expression plays important role in cellular functions. With
      the development of sequencing techniques, more and more genomes are available and
      genome-wide analyses of genomic structures that may affect gene expression
      regulation are now possible. Analyses of several genomes have found a class of
      regulatory regions that contain elements that initiate transcription of two
      different genes positioned with a head-to-head arrangement in two opposite
      directions. These regulatory regions are known as bidirectional promoters.
      Although bidirectional promoters have been known for years, recent genome-scale
      studies have shown that the regulation of the expression of up to 10% of the
      genes are controlled by bidirectional promoters. These findings are based mostly
      on computational work and only a limited number of putative bidirectional
      promoters have been experimentally validated. Developing methods to study
      bidirectional promoters will allow researchers to understand how these regions
      are regulated and the roles that divergent transcription plays in the expression
      of genes. Here, we have developed a novel dual-fluorescence reporter gene vector
      to study the transcriptional output of mammalian bidirectional promoters. We
      demonstrate that this vector is capable of expressing reporter genes under the
      control of bidirectional promoters, using the known human OSGEP/APEX
      bidirectional promoter. 

PMID- 24857938
TI  - Lesions in the posterior visual pathway promote trans-synaptic degeneration of
      retinal ganglion cells.
AB  - OBJECTIVE: Retrograde trans-synaptic degeneration of retinal ganglion cell layer
      (GCL) has been proposed as one of the mechanisms contributing to permanent
      disability after visual pathway damage. We set out to test this mechanism taking
      advantage of the new methods for imaging the macula with high resolution by
      optical coherence tomography (OCT) in patients with lesions in the posterior
      visual pathway. Additionally, we explored the association between thinning of GCL
      as an imaging marker of visual impairment such as visual field defects. METHODS:
      Retrospective case note review of patients with retrogeniculate lesions studied
      by spectral domain OCT of the macula and quadrant pattern deviation (PD) of the
      visual fields. RESULTS: We analysed 8 patients with either hemianopia or
      quadrantanopia due to brain lesions (stroke  = 5; surgery  = 2; infection  = 1).
      We found significant thinning of the GCL in the projecting sector of the retina
      mapping to the brain lesion. Second, we found strong correlation between the PD
      of the visual field quadrant and the corresponding macular GCL sector for the
      right (R = 0.792, p<0.001) and left eyes (R = 0.674, p<0.001). CONCLUSIONS: The
      mapping between lesions in the posterior visual pathway and their projection in
      the macula GCL sector corroborates retrograde trans-synaptic neuronal
      degeneration after brain injury as a mechanism of damage with functional
      consequences. This finding supports the use of GCL thickness as an imaging marker
      of trans-synaptic degeneration in the visual pathway after brain lesions.

PMID- 24857939
TI  - Leptin: new hope for the treatment of post-operative cognitive dysfunction?
AB  - Leptin plays a critical role in neuronal development and also promotes structural
      and functional activities in the central nervous system. Recent studies have
      demonstrated that leptin could produce therapeutic effects for cognitive
      impairments of patients with Alzheimer's disease (AD). Post-operative cognitive
      dysfunction (POCD), defined as a significant dysfunction in cognitive performance
      for several weeks after surgery, probably has a pathogenesis similar to that of
      AD. Specifically, they are both characterized by cognitive impairment. In this
      regard, we hypothesized that leptin probably has a therapeutic benefit of
      alleviating symptoms of patients with POCD, and the leptin signaling pathway may
      be involved in the pathogenesis of POCD.

PMID- 24857941
TI  - Characterizing EMG data using machine-learning tools.
AB  - Effective electromyographic (EMG) signal characterization is critical in the
      diagnosis of neuromuscular disorders. Machine-learning based pattern
      classification algorithms are commonly used to produce such characterizations.
      Several classifiers have been investigated to develop accurate and
      computationally efficient strategies for EMG signal characterization. This paper
      provides a critical review of some of the classification methodologies used in
      EMG characterization, and presents the state-of-the-art accomplishments in this
      field, emphasizing neuromuscular pathology. The techniques studied are grouped by
      their methodology, and a summary of the salient findings associated with each
      method is presented. 

PMID- 24857942
TI  - Assessing the vulnerability of Brazilian municipalities to the vectorial
      transmission of Trypanosoma cruzi using multi-criteria decision analysis.
AB  - Despite the dramatic reduction in Trypanosoma cruzi vectorial transmission in
      Brazil, acute cases of Chagas disease (CD) continue to be recorded. The
      identification of areas with greater vulnerability to the occurrence of vector
      borne CD is essential to prevention, control, and surveillance activities. In the
      current study, data on the occurrence of domiciliated triatomines in Brazil (non
      Amazonian regions) between 2007 and 2011 were analyzed. Municipalities'
      vulnerability was assessed based on socioeconomic, demographic, entomological,
      and environmental indicators using multi-criteria decision analysis (MCDA).
      Overall, 2275 municipalities were positive for at least one of the six triatomine
      species analyzed (Panstrongylus megistus, Triatoma infestans, Triatoma
      brasiliensis, Triatoma pseudomaculata, Triatoma rubrovaria, and Triatoma
      sordida). The municipalities that were most vulnerable to vector-borne CD were
      mainly in the northeast region and exhibited a higher occurrence of domiciliated
      triatomines, lower socioeconomic levels, and more extensive anthropized areas.
      Most of the 39 new vector-borne CD cases confirmed between 2001 and 2012 in non
      Amazonian regions occurred within the more vulnerable municipalities. Thus, MCDA
      can help to identify the states and municipalities that are most vulnerable to
      the transmission of T. cruzi by domiciliated triatomines, which is critical for
      directing adequate surveillance, prevention, and control activities. The
      methodological approach and results presented here can be used to enhance CD
      surveillance in Brazil. 

PMID- 24857943
TI  - Impotence: a frustratingly elusive target.

PMID- 24857944
TI  - The role of accessory obturator arteries in prostatic arterial embolization.
AB  - In 9 of 491 patients (1.8%) who underwent prostatic arterial embolization (PAE)
      for benign prostatic hyperplasia from March 2009-November 2013, prostatic
      arteries arose from the external iliac artery via an accessory obturator artery
      (AOA). Computed tomography angiography performed before the procedure identified
      the variant and allowed planning before the procedure. The nine AOAs were
      catheterized from a contralateral femoral approach. Bilateral PAE was technically
      successful in the nine patients. There was a mean decrease in international
      prostate symptom score of 6.5 points and a mean prostate volume reduction of
      15.1% (mean follow-up, 4.8 mo) in the nine patients. 

PMID- 24857945
TI  - Acute hand ischemia after unintentional intraarterial injection of drugs: is
      catheter-directed thrombolysis useful?
AB  - Unintentional intraarterial injections are rare but may have devastating
      consequences. No consensus on treatment has been established owing to the wide
      variety of possible injected substances, incomplete understanding of the
      underlying pathophysiology, and the absence of case-controlled, prospective human
      studies. The aim of the present study and literature review was to evaluate the
      benefit of intraarterial thrombolysis combined with systemic anticoagulation
      therapy when an artery of the upper extremity is accidentally punctured and
      ischemia of the hand ensues. 

PMID- 24857946
TI  - Percutaneous transhepatic stent graft placement for treatment of hepatic artery
      injury after a Whipple procedure.

PMID- 24857947
TI  - Femoral removal of Meridian filter in a patient with central venous occlusion.

PMID- 24857948
TI  - Blunt breast trauma treated with endovascular embolization.

PMID- 24857950
TI  - FBI-1 enhances ETS-1 signaling activity and promotes proliferation of human
      colorectal carcinoma cells.
AB  - In this study, we investigated a potential regulatory role of FBI-1 in
      transcription factor activity of ETS-1. The protein interaction was identified
      between ETS-1 and FBI-1 in lovo cells. The accumulating data showed that FBI-1
      promoted the recruitment of ETS-1 to endogenous promoter of its target genes and
      increase ETS-1 accumulation in the nuclear. Our work also indicated that the FBI
      1 enhances ETS-1 transcription factor activity via down-regulating p53-mediated
      inhibition on ETS-1. Further, FBI-1 plays a role in regulation of colorectal
      carcinoma cells proliferation. These findings supported that FBI-1 might be a
      potential molecule target for treating colorectal carcinoma. 

PMID- 24857951
TI  - Causes and consequences of inherited cone disorders.
AB  - Hereditary cone disorders (CDs) are characterized by defects of the cone
      photoreceptors or retinal pigment epithelium underlying the macula, and include
      achromatopsia (ACHM), cone dystrophy (COD), cone-rod dystrophy (CRD), color
      vision impairment, Stargardt disease (STGD) and other maculopathies. Forty-two
      genes have been implicated in non-syndromic inherited CDs. Mutations in the 5
      genes implicated in ACHM explain ~93% of the cases. On the contrary, only 21% of
      CRDs (17 genes) and 25% of CODs (8 genes) have been elucidated. The fact that the
      large majority of COD and CRD-associated genes are yet to be discovered hints
      towards the existence of unknown cone-specific or cone-sensitive processes. The
      ACHM-associated genes encode proteins that fulfill crucial roles in the cone
      phototransduction cascade, which is the most frequently compromised (10 genes)
      process in CDs. Another 7 CD-associated proteins are required for transport
      processes towards or through the connecting cilium. The remaining CD-associated
      proteins are involved in cell membrane morphogenesis and maintenance, synaptic
      transduction, and the retinoid cycle. Further novel genes are likely to be
      identified in the near future by combining large-scale DNA sequencing and
      transcriptomics technologies. For 31 of 42 CD-associated genes, mammalian models
      are available, 14 of which have successfully been used for gene augmentation
      studies. However, gene augmentation for CDs should ideally be developed in large
      mammalian models with cone-rich areas, which are currently available for only 11
      CD genes. Future research will aim to elucidate the remaining causative genes,
      identify the molecular mechanisms of CD, and develop novel therapies aimed at
      preventing vision loss in individuals with CD in the future. 

PMID- 24857952
TI  - Mental health distress and related factors among prefectural public servants
      seven months after the great East Japan Earthquake.
AB  - BACKGROUND: To develop an empirically informed support measure for workers, we
      examined mental health distress and its risk factors among prefectural public
      servants who were affected by the Great East Japan Earthquake and faced a
      demanding workload in the midterm of the disaster. METHODS: We conducted a self
      administered health survey of all public servants in the Miyagi prefectural
      government two and seven months after the Great East Japan Earthquake (3743
      workers, 70.6% of all employees). We calculated odds ratios (ORs) and 95%
      confidence intervals (CIs) for mental distress (defined as K6 score >=10) in the
      domain of disaster-work-related stressors, work-related stressors, and disaster
      related stressors. RESULTS: Among those with better levels of workplace
      communication, the only factor that increased the risk of mental distress was not
      taking a non-work day each week (adjusted OR 2.55, 95% CI 1.27-5.14). Among those
      with poorer levels of workplace communication, in addition to not taking a non
      work day each week (adjusted OR 3.93, 95% CI 3.00-5.15), handling residents'
      complaints (adjusted OR 1.55, 95% CI 1.00-2.42), having dead or missing family
      members (adjusted OR 2.87, 95% CI 1.53-5.38), and living in a shelter more than
      two months after the disaster (adjusted OR 2.80, 95% CI 1.32-5.95) increased the
      risk of mental distress. CONCLUSIONS: All workers should be encouraged to take a
      non-work day each week. Among workers with poor workplace communication, special
      attention should be given to those who handle residents' complaints, have lost a
      family member(s), and are living in a shelter for a prolonged period of time.

PMID- 24857953
TI  - Acute effects of summer air pollution on pulmonary function and airway
      inflammation in healthy young women.
AB  - BACKGROUND: Exposure to air pollution has been reported to be associated with
      asthma exacerbation. However, little is known about the effects of air pollutant
      exposure in healthy people. A panel study was conducted to evaluate the acute
      effects of air pollutants on pulmonary function and airway inflammation in
      healthy subjects. METHODS: Exhaled breath condensate (EBC) pH, fractional
      concentration of exhaled nitric oxide (FeNO), and pulmonary function were
      measured in 21 healthy young women repeatedly for two weeks in the summer in
      Tokyo, Japan. The concentrations of air pollutants were obtained from the
      monitoring stations in the neighborhoods where the subjects lived. Statistical
      analyses were performed using generalized estimating equations. RESULTS: EBC pH
      decreased significantly with a 10-ppb increase in the 4-day average ozone (O3)
      concentration and a 10-ug/m3 increase in the 4-day average suspended particulate
      matter (SPM) concentration (-0.07 [95% confidence interval {CI} -0.11 to -0.03]
      and -0.08 [95% CI -0.12 to -0.03], respectively). Subjects with a history of
      rhinitis showed marked decreases in EBC pH associated with increases in O3 and
      SPM. The changes in forced expiratory volume in 1 second (FEV1) were also
      significantly associated with a 10-ug/m3 increase in the 3-day average
      concentration of SPM (-0.09 L [95% CI -0.17 to -0.01]). FeNO increased
      significantly in relation to the increase in O3 and SPM among only subjects with
      a history of asthma. CONCLUSIONS: Over the course of the study, EBC became
      significantly acidic with increases in O3 and SPM concentrations. Furthermore,
      higher SPM concentrations were associated with decreased FEV1. Subjects with a
      history of rhinitis or asthma are considered to be more susceptible to air
      pollutants.

PMID- 24857954
TI  - Low intake of vegetables and fruits and risk of colorectal cancer: the Japan
      Collaborative Cohort Study.
AB  - BACKGROUND: The evidence for an association between low intake of vegetables and
      fruits and increased colorectal cancer risk is inconclusive. Evaluating the
      colorectal cancer risk associated with continued low intake is important.
      METHODS: We used data of 45 516 and 14 549 subjects aged 40-79 years obtained in
      the baseline and interim surveys, respectively, from the Japan Collaborative
      Cohort Study for Evaluation of Cancer Risk (JACC Study). The intake frequency of
      vegetables and fruits as assessed by a self-administered questionnaire was
      classified into tertiles of low, middle, and high groups, and the low group was
      subdivided into 2 equal groups (lower low and higher low groups). Colorectal
      cancer incidence determined from follow-up was used. Cox's proportional hazard
      model was employed to estimate the hazard ratios (HRs) and 95% confidence
      intervals (CIs), adjusting for covariates. RESULTS: During 598 605 person-years
      of subject follow-up after baseline, we identified 806 colorectal cancer cases.
      HRs for the lower low versus the middle and high intake frequencies of vegetables
      and fruits at baseline were 0.95 (95% CI 0.77-1.16) and 1.08 (95% CI 0.90-1.29),
      respectively. During 125 980 person-years of subject follow-up after the interim
      survey, 197 colorectal cancer cases were identified. HRs for the low versus
      middle and high intake frequencies of vegetables and fruits in both baseline and
      interim surveys were 0.91 (95% CI 0.61-1.37) and 0.87 (95% CI 0.59-1.27),
      respectively. CONCLUSIONS: Our results suggest that low intake and continued low
      intake of vegetables and fruits are not strongly associated with colorectal
      cancer risk.

PMID- 24857955
TI  - Prevalence of systemic lupus erythematosus in South Korea: an administrative
      database study.
AB  - BACKGROUND: Systemic lupus erythematosus (SLE) is a rare autoimmune disease for
      which a population-based survey on the prevalence of the disease in South Korea
      has not yet been conducted. Our goal was to estimate the nationwide prevalence of
      SLE. METHODS: The International Classification of Diseases, Tenth Revision (ICD
      10) code for SLE diagnosis-M32-was tentatively given when patients were suspected
      to have SLE before 2009. As such, the positive predictive value (PPV) of the M32
      code shown in medical bills reflecting true SLE was uncertain. We attempted to
      estimate the prevalence of SLE in South Korea using national administrative
      database data from 2004-2006. We approximated the actual number of SLE patients
      by analyzing a list of SLE-coded patients provided by the National Health
      Insurance (NHI) and Health Insurance Review and Assessment Service. Prevalence
      was estimated by multiplying the PPV of the M32 diagnostic code by the number of
      patients receiving the code. The PPV was determined by three methods: direct
      investigation of the medical records of patients randomly selected from the SLE
      coded patients list; assessment of all SLE patients treated at 56 selected
      hospitals in South Korea; and extrapolation from sub-groups at a single institute
      to the sub-groups of the national NHI data. RESULTS: The estimated number of
      national SLE cases was between 9000 and 11,000, depending on the method of
      ascertainment, corresponding to a prevalence of 18.8-21.7 per 100,000 people.
      CONCLUSIONS: This is the first report of a nationwide prevalence survey of SLE in
      South Korea. National databases may serve as a resource for epidemiologic studies
      of rare autoimmune diseases like SLE.

PMID- 24857956
TI  - Family history of hypertension and the risk of overweight in Japanese children:
      results from the Toyama Birth Cohort Study.
AB  - BACKGROUND: Family history can be a useful screening tool in the assessment and
      management of the risk for noncommunicable disease. However, no data have yet
      been reported on family history of hypertension and its effect on children's
      overweight. METHODS: A total of 7249 Japanese children enrolled in the Toyama
      Birth Cohort Study were followed until 2002 (mean age: 12.3 years). Family
      history of hypertension was ascertained by asking children's parents whether
      children's biological parents or grandparents had doctor-diagnosed hypertension.
      Child overweight was defined according to international criteria for age- and sex
      specific body mass index. RESULTS: The prevalence of child overweight at age 12
      was 21.7% for males and 15.9% for females. After adjusting for family structure,
      parental employment status, and lifestyle factors, we found that a maternal
      family history of hypertension was positively associated with the risk of child
      overweight at age 12 (adjusted odds ratio [OR] 1.21, 95% confidence interval [CI]
      1.04-1.39). The adjusted OR increased from 1.16 (95% CI 0.99-1.35) to 1.42 (95%
      CI 1.04-1.92) to 4.75 (95% CI 1.35-16.69) as the number of family members with
      hypertension increased from 1 to 2 to 3, respectively. There was no significant
      difference in the prevalence of overweight between children with a paternal
      family history of hypertension and those without. CONCLUSIONS: A maternal family
      history of hypertension was positively associated with the risk of overweight in
      children at age 12.

PMID- 24857958
TI  - Sex differences in the adult HPA axis and affective behaviors are altered by
      perinatal exposure to a low dose of bisphenol A.
AB  - Bisphenol A (BPA), an estrogen-mimicking endocrine disrupter, when administered
      perinatally can affect affective behaviors in adult rodents, however the
      underlying mechanisms remain largely unclear. Postnatal day (PND) 80 vehicle
      injected control female rats showed more obvious depression- and anxiety-like
      behaviors than males, indicative of sexually dimorphic affective behaviors. When
      female breeders were subcutaneously injected with BPA (2ug/kg) from gestation day
      10 to lactation day 7, sex difference of affective behaviors was impaired in
      their offspring (PND80 BPA-rats), as results that female BPA-rats showed a
      visible "antianxiety-like" behavior, and male BPA-rats increased depression-like
      behavior compared to vehicle-injected controls. Notably, basal levels of serum
      corticosterone and adrenocorticotropin (ACTH), and corticotropin-releasing
      hormone mRNA were increased in male BPA-rats, but not in female BPA-rats, in
      comparison with vehicle-injected controls. Following mild-stressor the elevation
      of corticosterone or ACTH levels was higher in male BPA-rats, whereas it was
      lower in female BPA-rats than vehicle-injected controls. In comparison with
      vehicle-injected controls, the level of glucocorticoid receptor (GR) mRNA in
      hippocampus or hypothalamic paraventricular nucleus was increased in female BPA
      rats, while decreased in male BPA-rats. In addition, the levels of hippocampal
      mineralocorticoid receptor (MR) mRNA, neuronal nitric oxide synthase (nNOS) and
      phospho-cAMP response element binding protein (p-CREB) were increased in female
      BPA-rats, but were decreased in male BPA-rats. Furthermore, the testosterone
      level was reduced in male BPA-rats. The results indicate that the perinatal
      exposure to BPA through altering the GR and MR expression disrupts the GR
      mediated feedback of hypothalamic-pituitary-adrenal (HPA) axis and MR-induced
      nNOS-CREB signaling, which alters sex difference in affective behaviors. 

PMID- 24857957
TI  - Coffee consumption and risk of colorectal cancer: the Japan Collaborative Cohort
      Study.
AB  - BACKGROUND: Epidemiologic studies have reported coffee consumption to be
      associated with various health conditions. The purpose of this study was to
      examine the relationship of coffee consumption with colorectal cancer incidence
      in a large-scale prospective cohort study in Japan. METHODS: We used data from
      the Japan Collaborative Cohort Study for Evaluation of Cancer Risk (JACC Study).
      Here, we analyzed a total of 58 221 persons (23 607 men, 34 614 women) followed
      from 1988 to the end of 2009. During 738 669 person-years of follow-up for the
      analysis of colorectal cancer risk with coffee consumption at baseline, we
      identified 687 cases of colon cancer (355 males and 332 females) and 314 cases of
      rectal cancer (202 males and 112 females). We used the Cox proportional-hazard
      regression model to estimate hazard ratio (HR). RESULTS: Compared to those who
      consumed less than 1 cup of coffee per day, men who consumed 2-3 cups of coffee
      per day had an HR of 1.26 (95% confidence interval [CI] 0.93-1.70), and men who
      consumed more than 4 cups of coffee per day had an HR of 1.79 (95% CI 1.01-3.18).
      A statistically significant increase in the risk of colon cancer was associated
      with increasing coffee consumption among men (P for trend = 0.03). On the other
      hand, coffee consumption in women was not associated with incident risk of colon
      cancer. Coffee consumption was also not associated with rectal cancer incidence
      in men or women. CONCLUSIONS: This large-scale population-based cohort study
      showed that coffee consumption increases the risk of colon cancer among Japanese
      men.

PMID- 24857960
TI  - Fermentation technologies for the optimization of marine microbial
      exopolysaccharide production.
AB  - In the last decades, research has focused on the capabilities of microbes to
      secrete exopolysaccharides (EPS), because these polymers differ from the
      commercial ones derived essentially from plants or algae in their numerous
      valuable qualities. These biopolymers have emerged as new polymeric materials
      with novel and unique physical characteristics that have found extensive
      applications. In marine microorganisms the produced EPS provide an instrument to
      survive in adverse conditions: They are found to envelope the cells by allowing
      the entrapment of nutrients or the adhesion to solid substrates. Even if the
      processes of synthesis and release of exopolysaccharides request high-energy
      investments for the bacterium, these biopolymers permit resistance under extreme
      environmental conditions. Marine bacteria like Bacillus, Halomonas, Planococcus,
      Enterobacter, Alteromonas, Pseudoalteromonas, Vibrio, Rhodococcus, Zoogloea but
      also Archaea as Haloferax and Thermococcus are here described as EPS producers
      underlining biopolymer hyperproduction, related fermentation strategies including
      the effects of the chemical composition of the media, the physical parameters of
      the growth conditions and the genetic and predicted experimental design tools. 

PMID- 24857959
TI  - Conotoxins targeting nicotinic acetylcholine receptors: an overview.
AB  - Marine snails of the genus Conus are a large family of predatory gastropods with
      an unparalleled molecular diversity of pharmacologically active compounds in
      their venom. Cone snail venom comprises of a rich and diverse cocktail of peptide
      toxins which act on a wide variety of ion channels such as voltage-gated sodium-
      (NaV), potassium- (KV), and calcium- (CaV) channels as well as nicotinic
      acetylcholine receptors (nAChRs) which are classified as ligand-gated ion
      channels. The mode of action of several conotoxins has been the subject of
      investigation, while for many others this remains unknown. This review aims to
      give an overview of the knowledge we have today on the molecular pharmacology of
      conotoxins specifically interacting with nAChRs along with the structure-function
      relationship data. 

PMID- 24857961
TI  - Tipping points in seaweed genetic engineering: scaling up opportunities in the
      next decade.
AB  - Seaweed genetic engineering is a transgenic expression system with unique
      features compared with those of heterotrophic prokaryotes and higher plants. This
      study discusses several newly sequenced seaweed nuclear genomes and the necessity
      that research on vector design should consider endogenous promoters, codon
      optimization, and gene copy number. Seaweed viruses and artificial transposons
      can be applied as transformation methods after acquiring a comprehensive
      understanding of the mechanism of viral infections in seaweeds and transposon
      patterns in seaweed genomes. After cultivating transgenic algal cells and tissues
      in a photobioreactor, a biosafety assessment of genetically modified (GM)
      seaweeds must be conducted before open-sea application. We propose a set of
      programs for the evaluation of gene flow from GM seaweeds to local/geographical
      environments. The effective implementation of such programs requires
      fundamentally systematic and interdisciplinary studies on algal physiology and
      genetics, marine hydrology, reproductive biology, and ecology. 

PMID- 24857962
TI  - Production of induced secondary metabolites by a co-culture of sponge-associated
      actinomycetes, Actinokineospora sp. EG49 and Nocardiopsis sp. RV163.
AB  - Two sponge-derived actinomycetes, Actinokineospora sp. EG49 and Nocardiopsis sp.
      RV163, were grown in co-culture and the presence of induced metabolites monitored
      by 1H NMR. Ten known compounds, including angucycline, diketopiperazine and beta
      carboline derivatives 1-10, were isolated from the EtOAc extracts of
      Actinokineospora sp. EG49 and Nocardiopsis sp. RV163. Co-cultivation of
      Actinokineospora sp. EG49 and Nocardiopsis sp. RV163 induced the biosynthesis of
      three natural products that were not detected in the single culture of either
      microorganism, namely N-(2-hydroxyphenyl)-acetamide (11), 1,6-dihydroxyphenazine
      (12) and 5a,6,11a,12-tetrahydro-5a,11a-dimethyl[1,4]benzoxazino[3,2
      b][1,4]benzoxazine (13a). When tested for biological activity against a range of
      bacteria and parasites, only the phenazine 12 was active against Bacillus sp.
      P25, Trypanosoma brucei and interestingly, against Actinokineospora sp. EG49.
      These findings highlight the co-cultivation approach as an effective strategy to
      access the bioactive secondary metabolites hidden in the genomes of marine
      actinomycetes.

PMID- 24857963
TI  - Klymollins T-X, bioactive eunicellin-based diterpenoids from the soft coral
      Klyxum molle.
AB  - Five new eunicellin-based diterpenoids, klymollins T-X (1-5), along with two
      known compounds (6 and 7) have been isolated from the soft coral Klyxum molle.
      The structures of these new metabolites were elucidated by extensive
      spectroscopic analysis and by comparison with related known compounds. Compound 5
      was found to exert significant in vitro anti-inflammatory activity against LPS
      stimulated RAW264.7 macrophage cells. Furthermore, compounds 4 and 7 were shown
      to exhibit cytotoxicity against a limited panel of human cancer cell lines. 

PMID- 24857964
TI  - Cracking the cytotoxicity code: apoptotic induction of 10-acetylirciformonin B is
      mediated through ROS generation and mitochondrial dysfunction.
AB  - A marine furanoterpenoid derivative, 10-acetylirciformonin B (10AB), was found to
      inhibit the proliferation of leukemia, hepatoma, and colon cancer cell lines,
      with selective and significant potency against leukemia cells. It induced DNA
      damage and apoptosis in leukemia HL 60 cells. To fully understand the mechanism
      behind the 10AB apoptotic induction against HL 60 cells, we extended our previous
      findings and further explored the precise molecular targets of 10AB. We found
      that the use of 10AB increased apoptosis by 8.9%-87.6% and caused disruption of
      mitochondrial membrane potential (MMP) by 15.2%-95.2% in a dose-dependent manner,
      as demonstrated by annexin-V/PI and JC-1 staining assays, respectively. Moreover,
      our findings indicated that the pretreatment of HL 60 cells with N-acetyl-l
      cysteine (NAC), a reactive oxygen species (ROS) scavenger, diminished MMP
      disruption and apoptosis induced by 10AB, suggesting that ROS overproduction
      plays a crucial rule in the cytotoxic activity of 10AB. The results of a cell
      free system assay indicated that 10AB could act as a topoisomerase catalytic
      inhibitor through the inhibition of topoisomerase IIalpha. On the protein level,
      the expression of the anti-apoptotic proteins Bcl-xL and Bcl-2, caspase
      inhibitors XIAP and survivin, as well as hexokinase II were inhibited by the use
      of 10AB. On the other hand, the expression of the pro-apoptotic protein Bax was
      increased after 10AB treatment. Taken together, our results suggest that 10AB
      induced apoptosis is mediated through the overproduction of ROS and the
      disruption of mitochondrial metabolism.

PMID- 24857967
TI  - Are we myopic about myopia control?

PMID- 24857966
TI  - TU-100 (Daikenchuto) and ginger ameliorate anti-CD3 antibody induced T cell
      mediated murine enteritis: microbe-independent effects involving Akt and NF
      kappaB suppression.
AB  - The Japanese traditional medicine daikenchuto (TU-100) has anti-inflammatory
      activities, but the mechanisms remain incompletely understood. TU-100 includes
      ginger, ginseng, and Japanese pepper, each component possessing bioactive
      properties. The effects of TU-100 and individual components were investigated in
      a model of intestinal T lymphocyte activation using anti-CD3 antibody. To
      determine contribution of intestinal bacteria, specific pathogen free (SPF) and
      germ free (GF) mice were used. TU-100 or its components were delivered by diet or
      by gavage. Anti-CD3 antibody increased jejunal accumulation of fluid, increased
      TNFalpha, and induced intestinal epithelial apoptosis in both SPF and GF mice,
      which was blocked by either TU-100 or ginger, but not by ginseng or Japanese
      pepper. TU-100 and ginger also blocked anti-CD3-stimulated Akt and NF-kappaB
      activation. A co-culture system of colonic Caco2BBE and Jurkat-1 cells was used
      to examine T-lymphocyte/epithelial cells interactions. Jurkat-1 cells were
      stimulated with anti-CD3 to produce TNFalpha that activates epithelial cell NF
      kappaB. TU-100 and ginger blocked anti-CD3 antibody activation of Akt in Jurkat
      cells, decreasing their TNFalpha production. Additionally, TU-100 and ginger
      alone blocked direct TNFalpha stimulation of Caco2BBE cells and decreased
      activation of caspase-3 and polyADP ribose. The present studies demonstrate a new
      anti-inflammatory action of TU-100 that is microbe-independent and due to its
      ginger component. 

PMID- 24857965
TI  - Chaos and commotion in the wake of cortical spreading depression and spreading
      depolarizations.
AB  - Punctuated episodes of spreading depolarizations erupt in the brain, encumbering
      tissue structure and function, and raising fascinating unanswered questions
      concerning their initiation and propagation. Linked to migraine aura and
      headache, cortical spreading depression contributes to the morbidity in the
      world's migraine with aura population. Even more ominously, erupting spreading
      depolarizations accelerate tissue damage during brain injury. The once-held view
      that spreading depolarizations may not exist in the human brain has changed,
      largely because of the discovery of migraine genes that confer cortical spreading
      depression susceptibility, the application of sophisticated imaging tools and
      efforts to interrogate their impact in the acutely injured human brain.

PMID- 24857968
TI  - Comments on the published article: "Distribution of normal superficial ocular
      vessels in digital images, Banaee et al. (2014)".

PMID- 24857969
TI  - HeteroGenome: database of genome periodicity.
AB  - We present the first release of the HeteroGenome database collecting latent
      periodicity regions in genomes. Tandem repeats and highly divergent tandem
      repeats along with the regions of a new type of periodicity, known as profile
      periodicity, have been collected for the genomes of Saccharomyces cerevisiae,
      Arabidopsis thaliana, Caenorhabditis elegans and Drosophila melanogaster. We
      obtained data with the aid of a spectral-statistical approach to search for
      reliable latent periodicity regions (with periods up to 2000 bp) in DNA
      sequences. The original two-level mode of data presentation (a broad view of the
      region of latent periodicity and a second level indicating conservative fragments
      of its structure) was further developed to enable us to obtain the estimate,
      without redundancy, that latent periodicity regions make up ~10% of the analyzed
      genomes. Analysis of the quantitative and qualitative content of located
      periodicity regions on all chromosomes of the analyzed organisms revealed
      dominant characteristic types of periodicity in the genomes. The pattern of
      density distribution of latent periodicity regions on chromosome unambiguously
      characterizes each chromosome in genome. Database URL:
      http://www.jcbi.ru/lp_baze/

PMID- 24857970
TI  - PTM-SD: a database of structurally resolved and annotated posttranslational
      modifications in proteins.
AB  - Posttranslational modifications (PTMs) define covalent and chemical modifications
      of protein residues. They play important roles in modulating various biological
      functions. Current PTM databases contain important sequence annotations but do
      not provide informative 3D structural resource about these modifications.
      Posttranslational modification structural database (PTM-SD) provides access to
      structurally solved modified residues, which are experimentally annotated as
      PTMs. It combines different PTM information and annotation gathered from other
      databases, e.g. Protein DataBank for the protein structures and dbPTM and
      PTMCuration for fine sequence annotation. PTM-SD gives an accurate detection of
      PTMs in structural data. PTM-SD can be browsed by PDB id, UniProt accession
      number, organism and classic PTM annotation. Advanced queries can also be
      performed, i.e. detailed PTM annotations, amino acid type, secondary structure,
      SCOP class classification, PDB chain length and number of PTMs by chain.
      Statistics and analyses can be computed on a selected dataset of PTMs. Each PTM
      entry is detailed in a dedicated page with information on the protein sequence,
      local conformation with secondary structure and Protein Blocks. PTM-SD gives
      valuable information on observed PTMs in protein 3D structure, which is of great
      interest for studying sequence-structure- function relationships at the light of
      PTMs, and could provide insights for comparative modeling and PTM predictions
      protocols. Database URL: PTM-SD can be accessed at
      http://www.dsimb.inserm.fr/dsimb_tools/PTM-SD/.

PMID- 24857972
TI  - The role of endplate poromechanical properties on the nutrient availability in
      the intervertebral disc.
AB  - OBJECTIVE: To investigate the relevance of the human vertebral endplate
      poromechanics on the fluid and metabolic transport from and to the intervertebral
      disc (IVD) based on educated estimations of the poromechanical parameter values
      of the bony endplate (BEP). METHODS: 50 micro-models of different BEP samples
      were generated from MUCTs of lumbar vertebrae and allowed direct determination of
      porosity values. Permeability values were calculated by using the micro-models,
      through the simulation of permeation via computational fluid dynamics. These
      educated ranges of porosity and permeability values were used as inputs for
      mechano-transport simulations to assess their effect on both the distributions of
      metabolites within an IVD model and the poromechanical calculations within the
      cartilaginous part of the endplate i.e., the cartilage endplate (CEP). RESULTS:
      BEP effective permeability was highly correlated to local variations of porosity
      (R(2) ~ 0.88). Universal patterns between bone volume fraction and permeability
      arose from these results and from other experimental data in the literature.
      These variations in BEP permeability and porosity had negligible effects on the
      distributions of metabolites within the disc. In the CEP, the variability of the
      poromechanical properties of the BEP did not affect the predicted consolidation
      but induced higher fluid velocities. CONCLUSIONS: The present paper provides the
      first sets of thoroughly identified BEP parameter values that can be further used
      in patient-specific poromechanical studies. Representing BEP structural changes
      through variations in poromechanical properties did not affect the diffusion of
      metabolites. However, attention might be paid to alterations in fluid velocities
      and cell mechano-sensing within the CEP.

PMID- 24857971
TI  - Oral and vaginal epithelial cell lines bind and transfer cell-free infectious HIV
      1 to permissive cells but are not productively infected.
AB  - The majority of HIV-1 infections worldwide are acquired via mucosal surfaces.
      However, unlike the vaginal mucosa, the issue of whether the oral mucosa can act
      as a portal of entry for HIV-1 infection remains controversial. To address
      potential differences with regard to the fate of HIV-1 after exposure to oral and
      vaginal epithelium, we utilized two epithelial cell lines representative of
      buccal (TR146) and pharyngeal (FaDu) sites of the oral cavity and compared them
      with a cell line derived from vaginal epithelium (A431) in order to determine (i)
      HIV-1 receptor gene and protein expression, (ii) whether HIV-1 genome integration
      into epithelial cells occurs, (iii) whether productive viral infection ensues,
      and (iv) whether infectious virus can be transferred to permissive cells. Using
      flow cytometry to measure captured virus by HIV-1 gp120 protein detection and
      western blot to detect HIV-1 p24 gag protein, we demonstrate that buccal,
      pharyngeal and vaginal epithelial cells capture CXCR4- and CCR5-utilising virus,
      probably via non-canonical receptors. Both oral and vaginal epithelial cells are
      able to transfer infectious virus to permissive cells either directly through
      cell-cell attachment or via transcytosis of HIV-1 across epithelial cells.
      However, HIV-1 integration, as measured by real-time PCR and presence of early
      gene mRNA transcripts and de novo protein production were not detected in either
      epithelial cell type. Importantly, both oral and vaginal epithelial cells were
      able to support integration and productive infection if HIV-1 entered via the
      endocytic pathway driven by VSV-G. Our data demonstrate that under normal
      conditions productive HIV-1 infection of epithelial cells leading to progeny
      virion production is unlikely, but that epithelial cells can act as mediators of
      systemic viral dissemination through attachment and transfer of HIV-1 to
      permissive cells. 

PMID- 24857973
TI  - Influences of alignment and obesity on knee joint loading in osteoarthritic gait.
AB  - OBJECTIVE: To determine the influences of frontal plane knee alignment and
      obesity on knee joint loads in older, overweight and obese adults with knee
      osteoarthritis (OA). METHODS: Cross-sectional investigation of alignment and
      obesity on knee joint loads using community dwelling older adults (age >= 55
      years; 27 kg m(-2) >= body mass or body mass index (BMI) <= 41 kg m(-2); 69%
      female) with radiographic knee OA that were a subset of participants (157 out of
      454) enrolled in the Intensive Diet and Exercise for Arthritis (IDEA) clinical
      trial. RESULTS: A higher BMI was associated with greater (P = 0.0006) peak knee
      compressive forces [overweight, 2411 N (2182, 2639), class 1 obesity, 2772 N
      (2602, 2943), class 2+ obesity, 2993 N (2796, 3190)] and greater (P = 0.004)
      shear forces [overweight, 369 N (322, 415), class 1 obesity, 418 N (384, 453),
      class 2+ obesity, 472 N (432, 513)], independent of alignment, and varus
      alignment was associated (P < 0.0001) with greater peak external knee adduction
      moments, independent of BMI [valgus, 18.7 Nm (15.1, 22.4), neutral, 27.7 Nm
      (24.0, 31.4), varus, 37.0 Nm (34.4, 39.7)]. CONCLUSION: BMI and alignment were
      associated with different joint loading measures; alignment was more closely
      associated with the asymmetry or imbalance of loads across the medial and lateral
      knee compartments as reflected by the frontal plane external adduction moment,
      while BMI was associated with the magnitude of total tibiofemoral force. These
      data may be useful in selecting treatment options for knee OA patients (e.g.,
      diet to reduce compressive loads or bracing to change alignment).

PMID- 24857974
TI  - The disease modifying osteoarthritis drug diacerein is able to antagonize pro
      inflammatory state of chondrocytes under mild mechanical stimuli.
AB  - OBJECTIVE: To investigate the combination of mild mechanical stimuli and a
      disease modifying osteoarthritis drug (DMOAD) in inflammatory activated
      chondrocytes and to study the combination of drug and mechanical tension on the
      cellular level as a model for an integrated biophysical approach for
      osteoarthritis (OA) treatments. METHODS: Interleukin-1beta (IL-1beta) stimulated
      C28/I2 cells underwent mild mechanically treatment while cultured in the presence
      of the DMOAD diacerein. The pharmacological input of diacerein was evaluated by
      cell viability and cell proliferation measurements. Inflammation and treatment
      induced changes in key regulatory proteins and components of the extracellular
      matrix (ECM) were characterized by quantitative real-time PCR (qPCR). The effects
      on metalloproteinase-1 (MMP-1) activity and glycosaminoglycan (GAG) concentration
      in cell supernatants of treated cells were investigated. RESULTS: C28/I2 cells
      demonstrated significant changes in expression of inflammatory and cartilage
      destructive proteins in response to IL-1beta stimulation. The chondroprotective
      action of diacerein in mechanically stimulated cells was mediated by a decrease
      in interleukin-8 (IL-8), fibronectin-1 (FN-1), collagen type I (Col 1) and MMP-1
      expression levels, respectively. Augmented expression of interleukin-6 receptor
      (IL-6R) and the fibroblast growth factor receptors (FGFRs) by diacerein was not
      abolished by mechanical treatment. The observed effects were accompanied by a
      reduced cell proliferation rate, attenuated cell viability and extenuated MMP-1
      activity. CONCLUSION: Diacerein diversely regulates the expression of main
      regulatory proteins as well as components important to regenerate and set up ECM.
      Mechanical stimulation does not negatively influence the chondroprotective effect
      induced by diacerein treatment in immortalized human C28/I2 chondrocytes.

PMID- 24857975
TI  - Destabilization of the medial meniscus leads to subchondral bone defects and site
      specific cartilage degeneration in an experimental rat model.
AB  - OBJECTIVE: This study aimed to investigate subchondral bone changes using micro
      computed tomography (micro-CT) and regional differences in articular cartilage
      degeneration, focusing on changes of cartilage covered by menisci, in the early
      phase using a destabilization of the medial meniscus (DMM) model. METHOD: The DMM
      model was created as an experimental rat osteoarthritis (OA) model (12 weeks old;
      n = 24). At 1, 2, and 4 weeks after surgery, the rats were sacrificed, and knee
      joints were scanned using a Micro-CT system. Histological sections of the medial
      tibial plateau, which was divided into inner, middle, and outer regions, were
      prepared and scored using the modified OARSI scoring system. The cartilage
      thickness was also calculated, and matrix metalloproteinase 13 (MMP13), Col2
      3/4c, and vascular endothelial growth factor (VEGF) expression was assessed
      immunohistochemically. RESULTS: Subchondral bone defects were observed in the
      middle region, in which the cartilage thickness decreased over time after
      surgery, and these defects were filled with MMP13- and VEGF-expressing fibrous
      tissue. The OARSI score increased over time in the middle region, and the score
      was significantly higher in the middle region than in the inner and outer regions
      at 1, 2, and 4 weeks after surgery. Col2-3/4c and MMP13 expression was observed
      primarily in the meniscus-covered outer region, in which the cartilage thickness
      increased over time. CONCLUSION: Loss of meniscal function caused cartilage
      degeneration and subchondral bone defects in the early phase site-specifically in
      the middle region. Furthermore, our results might indicate cartilage covered by
      menisci is easily degraded resulting in osmotic swelling of the cartilage in
      early OA.

PMID- 24857976
TI  - Changes in the metabolism of chondroitin sulfate glycosaminoglycans in articular
      cartilage from patients with Kashin-Beck disease.
AB  - OBJECTIVES: To identify changes in the expression patterns of enzymes involved in
      chondroitin sulfate (CS) glycosaminoglycan (GAG) metabolism in articular
      cartilage proteoglycan (PG) isolated from adolescent patients with Kashin-Beck
      disease (KBD). METHODS: Samples of articular cartilage were divided into two
      groups: Control samples (from five normal children), and KBD samples (from five
      KBD children) aged 3-12 years old. The morphology and pathology of hand joint
      cartilage were examined by histochemical staining. The localization and
      expression patterns of enzymes involved in CS GAG metabolism (i.e., PAPS
      synthetase 2 (PAPSS2), PAPS transporter 1 (PAPST1), Carbohydrate (N
      acetylgalactosamine 4-sulfate 6-O) sulfotransferases 15 (CHST15), Arylsulfatase B
      (ARSB) and N-acetylgalactosamine-6-sulfate sulfatase (GALNS)) were performed
      using immuno-histochemical analyses. Positive immunostaining in articular
      cartilage was semi-quantified. RESULTS: Reduced aggrecan staining was observed in
      KBD samples compared with the control samples. The percentages of positive
      staining for the anabolic enzymes PAPSS2, PAPST1 and CHST15 in the upper and
      middle zones of KBD samples were significantly lower than that found in the
      Controls. In contrast, the percentages of positive staining in KBD samples for
      the catabolic enzymes ARSB and GALNS were significantly higher than the control
      samples. However, the staining for all of these GAG metabolism enzymes were
      hardly observed in the deep zones of KBD cartilage, suggesting that significant
      cell death and necrosis had occurred in this region. CONCLUSIONS: Our results
      indicate that alterations of enzymes involved in articular cartilage CS GAG
      metabolism on PGs in the articular cartilage play an important role in the onset
      and pathogenesis of KBD in adolescent children.

PMID- 24857977
TI  - Inter-observer reliability for radiographic assessment of early osteoarthritis
      features: the CHECK (cohort hip and cohort knee) study.
AB  - OBJECTIVE: To calculate inter-observer reliability between four different trained
      readers and an experienced reader on early radiographic osteoarthritis (OA)
      features in our early OA cohort hip and cohort knee (CHECK) cohort. METHODS: Four
      readers were trained by a radiologist and experienced reader to score
      radiographic OA features. After this training they scored the CHECK cohort. Of
      the 1002 participants, 38 were scored by all readers. Five different angle
      radiographs (three for the knee, two for the hip) at three different time points
      were scored and compared. Inter-observer reliability was evaluated between each
      of the four trained readers and the experienced reader. Separate radiographic OA
      features and of overall Kellgren & Lawrence (K&L) scores. In addition,
      reliability of progression of radiographic was determined in K&L scores and joint
      space narrowing (JSN). RESULTS: For hip and knee there was substantial inter
      observer reliability on overall K&L scores. In the knee, JSN was scored with fair
      to moderate reliability, osteophytes with moderate to nearly perfect reliability,
      and other features with fair to substantial reliability. In the hip, reliability
      ranged from substantial to nearly perfect. Moderate inter-observer reliability
      was found for progression of OA in both knee and hip, with slightly better
      reliability for progression based on K&L scores than on separate features.
      CONCLUSION: Good inter-observer reliability can be achieved between trained
      readers and an experienced reader. Although JSN in the knee is scored with lower
      inter-observer reliability than osteophytes, this does not seem to influence
      overall K&L scoring. In the hip all features showed good reliability.

PMID- 24857978
TI  - Size and shape of the lunate surface in different types of pincer impingement:
      theoretical implications for surgical therapy.
AB  - OBJECTIVE: Acetabular rim trimming is indicated in pincer hips with an oversized
      lunate surface but could result in a critically decreased size of the lunate
      surface in pincer hips with acetabular malorientation. There is a lack of
      detailed three-dimensional anatomy of lunate surface in pincer hips. Therefore,
      we questioned how does (1) size and (2) shape of the lunate surface differ among
      hips with different types of pincer impingement? METHOD: We retrospectively
      compared size and shape of the lunate surface between acetabular retroversion (48
      hips), deep acetabulum (34 hips), protrusio acetabuli (seven hips), normal
      acetabuli (30 hips), and hip dysplasia (45 hips). Using magnetic resonance
      imaging (MRI) arthrography with radial slices we measured size in percentage of
      the femoral head coverage and shape using the outer (inner) center-edge angles
      and width of lunate surface. RESULTS: Hips with retroversion had a decreased size
      and deep hips had normal size of the lunate surface. Both had a normal shape of
      the outer acetabular rim. Protrusio hips had an increased size and a prominent
      outer acetabular rim. In all three types of pincer hips the acetabular fossa was
      increased. CONCLUSION: Size and shape of the lunate surface differs substantially
      among different types of pincer impingement. In contrast to hips with protrusio
      acetabuli, retroverted and deep hips do not have an increased size of the lunate
      surface. Acetabular rim trimming in retroverted and deep hips should be performed
      with caution. Based on our results, acetabular reorientation would theoretically
      be the treatment of choice in retroverted hips.

PMID- 24857979
TI  - Defensive behaviour of Apis mellifera against Vespa velutina in France: testing
      whether European honeybees can develop an effective collective defence against a
      new predator.
AB  - We investigated the prey-predator interactions between the European honeybee,
      Apis mellifera, and the invasive yellow-legged hornet, Vespa velutina, which
      first invaded France in 2004 and thereafter spread to neighbouring European
      countries (Spain, Portugal and Italy). Our goal was to determine how successfully
      honeybees are able to defend their colonies against their new predator in Europe.
      Experiments were conducted in the southwest of France-the point of entry of the
      hornet in Europe-under natural and semi-controlled field conditions. We
      investigated a total of eight apiaries and 95 colonies subjected to either low or
      high levels of predation. We analyzed hornet predatory behaviour and collective
      response of colonies under attack. The results showed that A. mellifera in France
      exhibit an inefficient and unorganized defence against V. velutina, unlike in
      other regions of Europe and other areas around the globe where honeybees have co
      evolved with their natural Vespa predators. 

PMID- 24857980
TI  - Persistence of behaviours in the Forced Swim Test in 3xTg-AD mice at advanced
      stages of disease.
AB  - Forced Swimming Test (FST) models behavioural despair in animals by loss of
      motivation to respond or the refusal to escape. The present study characterizes
      the behavioural responses of 12-month-old male 3xTg-AD mice in FST as compared to
      age-matched no-transgenic (NTg) mice. Paradoxical results were consistently found
      from what would be expected from their BPSD (Behavioural and Psychological
      Symptoms of Dementia)-like profile. The comprehensive analysis of the ethogram
      shown in the FST considered the intervals of the test (0-2 and 2-6min), all the
      elicited behavioural responses (immobility, swimming and climbing) and their
      features (total duration, frequency of episodes and mean duration). Both
      genotypes showed equal number of swimming episodes and climbing attempts during
      the first interval, that resulted in high swimming times, short climbing and
      scarce immobility. Thereafter, the NTg mice showed a behavioural shift over time
      and the immobility response showed up. In contrast, all the measures consistently
      evidenced that 3xTg-AD persisted with the previous behavioural pattern. Genotype
      differences consisted in less number of episodes of immobility and swimming, and
      a low immobility time in favour of swimming. No differences were found in
      'climbing' attempts. The behavioural response observed is discussed as a lack of
      ability of 3xTg-AD mice to shift behaviour over time that may result of poorest
      cognitive flexibility and copying with stress strategies more than behavioural
      despair per se. 

PMID- 24857982
TI  - p38 MAPK and ERK1/2 pathways are involved in the pro-apoptotic effect of
      notoginsenoside Ft1 on human neuroblastoma SH-SY5Y cells.
AB  - AIMS: This study aims to investigate the effect and the mechanisms of
      notoginsenoside Ft1, a natural compound exclusively found in P. notoginseng, on
      the proliferation and apoptosis of human neuroblastoma SH-SY5Y cells. MAIN
      METHODS: CCK-8 assay was used to assess the cell proliferation. Flow cytometry
      was performed to measure the cell cycle distribution and cell apoptosis. Hoechst
      33258 staining was conducted to confirm the morphological changes of apoptotic
      cells. Protein expression was detected by western blot analysis and caspase 3
      activity was measured by colorimetric assay kit. KEY FINDINGS: Among the saponins
      examined, Ft1 showed the best inhibitory effect on cell proliferation of SH-SY5Y
      cells with IC50 of 45MUM. Ft1 not only arrested the cell cycle at S, G2/M stages,
      but also promoted cell apoptosis, which was confirmed by Hoechst 33258 staining.
      Further studies demonstrated that Ft1 up-regulated the protein expressions of
      cleaved caspase 3, phospho-p53, p21, and cyclin B1, but down-regulated that of
      Bcl-2. Moreover, Ft1 enhanced the phosphorylation of ERK1/2, JNK and p38 MAPK.
      However, the phosphorylation of Jak2 and p85 PI3K was reduced by Ft1. Inhibitors
      of p38 MAPK and ERK1/2 but not JNK abrogated the up-regulated protein expressions
      of cleaved caspase 3, p21 and down-regulated protein expression of Bcl-2 as well
      as elevated caspase 3 activity induced by Ft1. SIGNIFICANCE: Ft1 arrested the
      proliferation and elicited the apoptosis of SH-SY5Y cells possibly via p38 MAPK
      and ERK1/2 pathways, which indicates the potential therapeutic effect of it on
      human neuroblastoma.

PMID- 24857983
TI  - Distinct interactions between actin and essential myosin light chain isoforms.
AB  - Binding of the utmost N-terminus of essential myosin light chains (ELC) to actin
      slows down myosin motor function. In this study, we investigated the binding
      constants of two different human cardiac ELC isoforms with actin. We employed
      circular dichroism (CD) and surface plasmon resonance (SPR) spectroscopy to
      determine structural properties and protein-protein interaction of recombinant
      human atrial and ventricular ELC (hALC-1 and hVLC-1, respectively) with alpha
      actin as well as alpha-actin with alanin-mutated ELC binding site (alpha
      actin(ala3)) as control. CD spectroscopy showed similar secondary structure of
      both hALC-1 and hVLC-1 with high degree of alpha-helicity. SPR spectroscopy
      revealed that the affinity of hALC-1 to alpha-actin (KD=575 nM) was significantly
      (p<0.01) lower compared with the affinity of hVLC-1 to alpha-actin (KD=186 nM).
      The reduced affinity of hALC-1 to alpha-actin was mainly due to a significantly
      (p<0.01) lower association rate (kon: 1,018 M(-1)s(-1)) compared with kon of the
      hVLC-1/alpha-actin complex interaction (2,908 M(-1)s(-1)). Hence, differential
      expression of ELC isoforms could modulate muscle contractile activity via
      distinct alpha-actin interactions.

PMID- 24857984
TI  - A novel delivery platform for therapeutic peptides.
AB  - Although many peptides have therapeutic effects against diverse disease, their
      short half-lives in vivo hurdle their application as drug candidates. To extend
      the short elimination half-lives of therapeutic peptides, we developed a novel
      delivery platform for therapeutic peptides using an anti-hapten antibody and its
      corresponding hapten. We selected cotinine because it is non-toxic, has a well
      studied metabolism, and is physiologically absent. We conjugated WKYMVm-NH2, an
      anti-sepsis therapeutic peptide, to cotinine and showed that the conjugated
      peptide in complex with an anti-cotinine antibody has a significantly improved in
      vivo half-life while retaining its therapeutic efficacy. We suggest that this
      novel delivery platform for therapeutic peptides will be very useful to develop
      effective peptide therapeutics. 

PMID- 24857985
TI  - Differential expression of extracellular-signal-regulated kinase 5 (ERK5) in
      normal and degenerated human nucleus pulposus tissues and cells.
AB  - Extracellular-signal-regulated kinase 5 (ERK5) is a member of the mitogen
      activated protein kinase (MAPK) family and regulates a wide variety of cellular
      processes such as proliferation, differentiation, necrosis, apoptosis and
      degeneration. However, the expression of ERK5 and its role in degenerated human
      nucleus pulposus (NP) is hitherto unknown. In this study, we observed the
      differential expression of ERK5 in normal and degenerated human nucleus pulposus
      tissues by using immunohistochemical staining and Western blot. Treatment of NP
      cells with Pro-inflammatory cytokine, TNF-alpha decreased ERK5 gene expression as
      well as NP marker gene expression; including the type II collagen and aggrecan.
      Suppression of ERK5 gene expression in NP cells by ERK5 siRNA resulted in
      decreased gene expression of type II collagen and aggrecan. Furthermore,
      inhibition of ERK5 activation by BIX02188 (5MUM) decreased the gene expression of
      type II collagen and aggrecan in NP cells. Our results document the expression of
      ERK5 in degenerated nucleus pulposus tissues, and suggest a potential involvement
      of ERK5 in human degenerated nucleus pulposus. 

PMID- 24857986
TI  - Knockdown of hepatoma-derived growth factor-related protein-3 induces apoptosis
      of H1299 cells via ROS-dependent and p53-independent NF-kappaB activation.
AB  - We previously identified hepatoma-derived growth factor-related protein-3 (HRP-3)
      as a radioresistant biomarker in p53 wild-type A549 cells and found that p53
      dependent induction of the PUMA pathway was a critical event in regulating the
      radioresistant phenotype. Here, we found that HRP-3 knockdown regulates the
      radioresistance of p53-null H1299 cells through a distinctly different molecular
      mechanism. HRP-3 depletion was sufficient to cause apoptosis of H1299 cells by
      generating substantial levels of reactive oxygen species (ROS) through inhibition
      of the Nrf2/HO-1 antioxidant pathway. Subsequent, ROS-dependent and p53
      independent NF-kappaB activation stimulated expression of c-Myc and Noxa
      proteins, thereby inducing the apoptotic machinery. Our results thus extend the
      range of targets for the development of new drugs to treat both p53 wild-type or
      p53-null radioresistant lung cancer cells. 

PMID- 24857987
TI  - Down-regulation of ATBF1 activates STAT3 signaling via PIAS3 in pacing-induced HL
      1 atrial myocytes.
AB  - Atrial fibrillation (AF) is progressive and is the most common clinical
      arrhythmia. It is associated with inflammatory changes characterized by signal
      transducer and activator of transcription 3 (STAT3) signaling. A zinc finger
      homeobox 3 (ZFHX3, also named AT-motif binding factor 1, ATBF1) gene variant has
      been found in patients with AF. However, the mechanism by which the ATBF1 leads
      to inflammation in AF remains unknown. The aim of this study was to investigate
      whether tachypacing induces a decrease in ATBF1 expression and then activates
      STAT3 signaling via protein inhibitor of activated STAT3 (PIAS3). Atrial (HL-1
      myocytes) cells were cultured in the presence of rapid electrical stimulations.
      In tachypaced HL-1 cells, we found that ATBF1 and PIAS3 protein levels were
      decreased, while the level of phosphorylated STAT3 (p-STAT3) was highly up
      regulated compared with that of total STAT3. Knockdown of ATBF1 enhanced this
      trend, while the overexpression of ATBF1 had the opposite effect. A binary
      complex of ATBF1 and PIAS3 was formed and then the DNA-binding ability of
      activated STAT3 was enhanced in tachypaced HL-1 cells. These data indicate that
      tachypacing decreased ATBF1, leading to enhanced STAT3 DNA-binding activity due
      to the reduced formation of a binary complex of ATBF1 and PIAS3.

PMID- 24857988
TI  - Detection of Puumala hantavirus antigen in human intestine during acute
      hantavirus infection.
AB  - BACKGROUND: Puumala virus (PUUV) is the most important hantavirus species in
      Central Europe. Nephropathia epidemica (NE), caused by PUUV, is characterized by
      acute renal injury (AKI) with thrombocytopenia and frequently gastrointestinal
      symptoms. METHODS: 456 patients with serologically and clinically confirmed NE
      were investigated at time of follow-up in a single clinic. The course of the NE
      was investigated using medical reports. We identified patients who had endoscopy
      with intestinal biopsy during acute phase of NE. Histopathological,
      immunohistochemical and molecular analyses of the biopsies were performed.
      RESULTS: Thirteen patients underwent colonoscopy or gastroscopy for abdominal
      pain, diarrhea, nausea and vomiting during acute phase of NE.
      Immunohistochemistry (IHC) revealed PUUV nucleocapsid antigen in 11 biopsies from
      8 patients; 14 biopsies from 5 patients were negative for PUUV nucleocapsid
      antigen. IHC localized PUUV nucleocapsid antigen in endothelial cells of
      capillaries or larger vessels in the lamina propria. Rate of AKI was not higher
      and severity of AKI was not different in the PUUV-positive compared to the PUUV
      negative group. All IHC positive biopsies were positive for PUUV RNA using RT
      PCR. Phylogenetic reconstruction revealed clustering of all PUUV strains from
      this study with viruses previously detected from the South-West of Germany. Long
      term outcome was favorable in both groups. CONCLUSIONS: In patients with NE, PUUV
      nucleocapsid antigen and PUUV RNA was detected frequently in the intestine. This
      finding could explain frequent GI-symptoms in NE patients, thus demonstration of
      a more generalized PUUV infection. The RT-PCR was an effective and sensitive
      method to detect PUUV RNA in FFPE tissues. Therefore, it can be used as a
      diagnostic and phylogenetic approach also for archival materials. AKI was not
      more often present in patients with PUUV-positive IHC. This last finding should
      be investigated in larger numbers of patients with PUUV infection.

PMID- 24857989
TI  - The World Health Organization's action plan on the road traffic injury pandemic:
      is there any action for orthopaedic trauma surgeons?
AB  - Road traffic crash-related death, injury, and chronic disability continue to be a
      major worldwide burden to drivers, pedestrians, and users of mass transit,
      especially in low- and middle-income countries (LMIC). Projections predict
      worsening of this burden, and while motorization of LMIC increases exponentially,
      a corresponding improvement in prehospital and acute in-hospital trauma care has
      not been seen. The WHO now has 2 programs that address different elements of this
      challenge, namely, the Violence and Injury Prevention department (prevention) and
      the Emergency and Essential Surgical Care project (treatment). Activities of
      Violence and Injury Prevention have included developing guidelines for
      prehospital and essential trauma care, whereas activities of the Emergency and
      Essential Surgical Care have included developing the Integrated Management of
      Emergency and Essential Surgical Care toolkit and a textbook, "Surgical Care at
      the District Hospital." Organized surgical institutions in high-income countries
      trauma associations, university departments, surgical nongovernmental
      organizations, etc.-can benefit from the infrastructure and tools the WHO has
      developed to better address the deficits in surgical services to improve the
      equitable distribution of surgical care services and resources to LMIC.

PMID- 24857990
TI  - Evidence gaps in the global decade of road traffic safety.
AB  - Road traffic accidents are a leading cause of global mortality. In March 2010,
      the United Nations General Assembly and the World Health Organization (WHO)
      officially proclaimed 2011-2020 as the "Decade of Action for Road Safety."
      Researchers must focus on vulnerable road users and low- and middle-income
      countries (LMICs) and should give preference to simple high-impact interventions
      likely to be inexpensive and widely applicable. Collaborative investigative
      networks should include LMICs, and economic evaluations should demonstrate the
      value of novel interventions in LMIC settings. Reliable data systems are
      essential to understand needs and outcomes, and knowledge translation studies
      should support effective implementation.

PMID- 24857991
TI  - Opportunities for knowledge translation in the decade of road traffic safety.
AB  - The United Nations has identified road traffic safety as an important objective
      for the decade 2011-2020. It has implemented a 5-tiered program: improving health
      care services, improving management of road safety, improving road network
      safety, improving vehicular safety, and improving road safety legislation. A
      small body of practical research has been generated by the medical and surgical
      (including orthopaedic) communities regarding the road traffic safety, but a
      substantial amount of work remains to be performed. This article will review
      published research in each of the 5 tiers of the Decade of Action for Road
      Traffic Safety and will identify areas where research is insufficient or absent,
      such that new research programming and funding can be developed.

PMID- 24857992
TI  - Leading by example: the role of international trauma organizations in global
      trauma initiatives.
AB  - As road traffic fatalities have emerged among the leading global threats to human
      health and safety, there is an imminent need for the mobilization of large
      medical organizations and private companies. Collectively, these partnerships can
      have a tremendous impact on road traffic safety through garnering funding for
      important initiatives, lobbying governments for policy reforms, and implementing
      organizational frameworks that foster the transfer of health-care knowledge to
      optimize trauma care in developing countries. In particular, concerted efforts by
      major orthopaedic associations can directly enable overwhelmed health-care
      systems to improve upon their prehospital care, emergency triage systems, trauma
      care protocols, and rehabilitation programs. The "SIGN" and "Broken Earth"
      programs serve as prime examples of the powerful impact international trauma
      organizations can have on global trauma initiatives.

PMID- 24857993
TI  - Operationalizing an orthopedic action plan for the decade of road traffic safety.
AB  - The decade of action for road traffic safety provides orthopaedic surgeons with
      an opportunity to contribute to policy that will improve the ability to deliver
      trauma care. In the previous 2 decades outcomes for orthopaedic trauma patients
      have improved significantly. The decade of action for road traffic safety will
      bring attention and funding to trauma related endeavors. The challenge before
      orthopaedic surgeons and orthopaedic trauma societies is to provide delivery
      mechanisms so that clinical care can reach populations around the globe.
      Organizing orthopaedic trauma care into care delivery value chains provides a
      tool for understanding how efficiency can be gained over the entire cycle of care
      from emergent management through rehabilitation and revision surgery when needed.
      Integrated practice units allow orthopaedic surgeons to collaborate with other
      trauma specialists to provide integrated care and exploit the areas of natural
      overlap to create trauma care systems that optimize communication for surgeons
      and simplify follow up for patients. By using these tools orthopaedic surgeons
      can deliver excellent trauma care to populations around the world.

PMID- 24857994
TI  - Operationalizing an orthopaedic research plan in the Decade of Action for Road
      Safety: the INternational ORthopaedic MUlticenter Study in Fracture Care.

PMID- 24857995
TI  - Roads in India: safety and knowledge cross-sectional evaluation.
AB  - BACKGROUND: The World Health Organization estimates that more than 15% of the
      global burden of road traffic trauma is in India. We performed an image-based
      survey of 3 major roadways in New Delhi, India, to evaluate collision-prone
      vehicle and pedestrian behaviors. METHODS: We used a cross-sectional survey
      design with photograph- and video-based data collection. The study was performed
      at 3 purposively sampled high traffic volume roadways in New Delhi, India. The
      authors reviewed preliminary photographs and came to a consensus pertaining to
      the definition and criteria for dangerous and collision-prone behaviors. Analysis
      was descriptive and was based on frequency data. RESULTS: A total of 11,214
      subjects were evaluated. Eighty-six percent were vehicles (n = 9624), whereas the
      remaining 14% were pedestrians (n = 1572). In 99% of the frames, 1 or more
      predefined behavioral infraction was identified, with a total of 21% (n = 2392)
      of subjects committing these infractions. Specifically, 15% of all vehicles (n =
      1468) and 59% of all pedestrians (n = 924) displayed a risk-taking infraction.
      CONCLUSIONS: Road users in New Delhi, India, engage in unacceptably high rates of
      collision-prone behavior. There is a need for interventions that will improve the
      behaviors of road users.

PMID- 24857996
TI  - Status of road safety and injury burden: North America.

PMID- 24857997
TI  - Status of road safety and injury burden: Europe.

PMID- 24857998
TI  - Status of road safety and injury burden: China.

PMID- 24857999
TI  - Status of road safety and injury burden: Brazil.

PMID- 24858000
TI  - Status of road safety and injury burden: Mexico.

PMID- 24858001
TI  - Status of road safety and injury burden: Africa.

PMID- 24858002
TI  - Status of road safety and injury burden: Vietnam.

PMID- 24858003
TI  - Editorial note: A decade of collaboration and action.

PMID- 24858004
TI  - Why a decade of road traffic safety?
AB  - Each year, 1.24 million people die as a result of road traffic collisions around
      the world, and millions more are left to suffer the resultant disabilities of
      their nonfatal typically musculoskeletal injuries. The most productive members of
      society are the ones affected the most, and the subsequent economic impact cannot
      be ignored. Reducing the morbidity and mortality associated with road traffic
      injuries will reduce suffering and increase available resources that can be used
      more effectively. Road traffic injuries are preventable, and the impact of those
      that do occur can be mitigated. Adequate national and global funding, strategy,
      and measurable targets are fundamental to a sustainable response to road safety.
      Over the last decade, the United Nations and World Health Organization have been
      part of the gaining momentum toward addressing this issue, through resolutions
      and coordinating global efforts. This is what brought about the "Decade of Action
      for Road Traffic Safety," and as orthopaedic surgeons, our involvement is key for
      the collaborative public health response toward this effort.

PMID- 24858005
TI  - Endocrinology and metabolism 2014.

PMID- 24858006
TI  - The Spitzenkorper: a choreographer of fungal growth and morphogenesis.
AB  - The Spitzenkorper (SPK) is a multicomponent pleomorphic structure found at hyphal
      apices. It is necessary to maintain hyphal growth and morphogenesis in numerous
      fungal species, including plant and human pathogens. At the turn of the 21st
      century extraordinary advances in protein tagging technology and live microscopy
      allowed uncovering the main molecular constituents of the SPK. Distinct layers of
      macrovesicles and microvesicles, each carrying different cell wall synthetic
      enzymes, along with the actin cytoskeleton and related proteins are some of the
      components that make up the SPK. One of the biggest current challenges is to
      decipher the functional relationship between the SPK components and
      macromolecular complexes, such as the polarisome and the exocyst, which partially
      co-localize within the hyphal dome. 

PMID- 24858007
TI  - Oxidative & nitrosative stress in depression: why so much stress?
AB  - Many studies support a crucial role for oxidative & nitrosative stress (O&NS) in
      the pathophysiology of unipolar and bipolar depression. These disorders are
      characterized inter alia by lowered antioxidant defenses, including: lower levels
      of zinc, coenzyme Q10, vitamin E and glutathione; increased lipid peroxidation;
      damage to proteins, DNA and mitochondria; secondary autoimmune responses directed
      against redox modified nitrosylated proteins and oxidative specific epitopes.
      This review examines and details a model through which a complex series of
      environmental factors and biological pathways contribute to increased redox
      signaling and consequently increased O&NS in mood disorders. This multi-step
      process highlights the potential for future interventions that encompass a
      diverse range of environmental and molecular targets in the treatment of
      depression. 

PMID- 24858008
TI  - Vagus nerve stimulation...25 years later! What do we know about the effects on
      cognition?
AB  - VNS therapy was delivered to patients for the first time in 1988. After 25 years,
      insight in the antiepileptic and antidepressant mechanism of action of VNS has
      grown steadily. The effects on cognition and especially memory remain
      controversial. This review provides an elaborate overview of studies addressing
      cognition and describes potential underlying mechanisms for the reported effects.
      Short-term VNS has an effect on verbal memory recognition when administered at
      the correct timing and dosage. Chronic VNS resulted into a positive effect on the
      cognitive status in an Alzheimer population. Positive effect of chronic VNS in
      epilepsy or depression patients on global cognitive functioning are less
      convincing. Neither do the results reveal a negative effect which has major
      implications for chronic treatment of neurology patients. A cascade of
      neurochemical processes put in motion by changes in NE concentrations in reaction
      to stimulation of the vagal nerve may underlie the VNS-induced effects on
      cognition and memory. In Alzheimer pathology, NE may act as an anti-inflammatory
      agent on brainstem nuclei. 

PMID- 24858009
TI  - Lateralized perception: the role of attention in spatial relation processing.
AB  - Any spatial situation can be approached either categorically - the window is to
      my left - or coordinately - the glass is 20cm away from the bottle. Since the
      first description of the distinction between categorical and coordinate spatial
      relation processing, it has often been shown that they are processed by at least
      partially different underlying mechanisms, mainly located in the left and right
      hemisphere, respectively. A number of recent studies have suggested that spatial
      attention plays a particularly important part in the perception of space:
      categorical processing benefits from a local focus of attention, and coordinate
      processing profits from a global focus of attention. This suggests that the
      lateralization pattern is modified by the concurrent size of the attentional
      focus, and is consequently more dynamic than previously thought. Therefore, a
      thorough revision of earlier theories on spatial relation processing is in order.
      In this review, we present a new model on lateralization of spatial relation
      processing that explicitly describes the role of spatial attention. 

PMID- 24858010
TI  - Localization of kainate receptors in inner and outer hair cell synapses.
AB  - Glutamate plays a role in hair cell afferent transmission, but the receptors that
      mediate neurotransmission between outer hair cells (OHCs) and type II ganglion
      neurons are not well defined. A previous study using in situ hybridization showed
      that several kainate-type glutamate receptor (KAR) subunits are expressed in
      cochlear ganglion neurons. To determine whether KARs are expressed in hair cell
      synapses, we performed X-gal staining on mice expressing lacZ driven by the GluK5
      promoter, and immunolabeling of glutamate receptors in whole-mount mammalian
      cochleae. X-gal staining revealed GluK5 expression in both type I and type II
      ganglion neurons and OHCs in adults. OHCs showed X-gal reactivity throughout
      maturation from postnatal day 4 (P4) to 1.5 months. Immunoreactivity for GluK5 in
      IHC afferent synapses appeared to be postsynaptic, similar to GluA2 (GluR2; AMPA
      type glutamate receptor (AMPAR) subunit), while GluK2 may be on both sides of the
      synapses. In OHC afferent synapses, immunoreactivity for GluK2 and GluK5 was
      found, although GluK2 was only in those synapses bearing ribbons. GluA2 was not
      detected in adult OHC afferent synapses. Interestingly, GluK1, GluK2 and GluK5
      were also detected in OHC efferent synapses, forming several active zones in each
      synaptic area. At P8, GluA2 and all KAR subunits except GluK4 were detected in
      OHC afferent synapses in the apical turn, and GluA2, GluK1, GluK3 decreased
      dramatically in the basal turn. These results indicate that AMPARs and KARs
      (GluK2/GluK5) are localized to IHC afferent synapses, while only KARs
      (GluK2/GluK5) are localized to OHC afferent synapses in adults. Glutamate
      spillover near OHCs may act on KARs in OHC efferent terminals to modulate
      transmission of acoustic information and OHC electromotility. 

PMID- 24858011
TI  - Maintenance use of antidepressants in Dutch general practice: non-guideline
      concordant.
AB  - BACKGROUND: There is hardly evidence on maintenance treatment with
      antidepressants in primary care. Nevertheless, depression guidelines recommend
      maintenance treatment i.e. treatment to prevent recurrences, in patients with
      high risk of recurrence, and many patients use maintenance treatment with
      antidepressants. This study explores the characteristics of patients on
      maintenance treatment with antidepressants in general practice, and compares
      these characteristics with guideline recommendations for maintenance treatment.
      METHODS: We used data (baseline, two-year and four-year follow-up) of primary
      care respondents with remitted depressive disorder (>=6 months) from the
      Netherlands Study of Depression and Anxiety (n = 776). Maintenance treatment was
      defined as the use of an antidepressant for >=12 months. Multilevel logistic
      regression was used to describe the association between sociodemographic,
      clinical and care characteristics and use of maintenance treatment with
      antidepressants. RESULTS: Older patients, patients with a lower education, those
      using benzodiazepines or receiving psychological/psychiatric care and patients
      with a concurrent history of a dysthymic or anxiety disorder more often received
      maintenance treatment with antidepressants. LIMITATIONS: Measurements were not
      made at the start of an episode, but at predetermined points in time. Diagnoses
      were based on interview (CIDI) data and could therefore in some cases have been
      different from the GP diagnosis. CONCLUSIONS: Since patients with chronic or
      recurrent depression do not use maintenance treatment with antidepressants more
      often, characteristics of patients on maintenance treatment do not fully
      correspond with guideline recommendations. However, patients on maintenance
      treatment appear to be those with more severe disorder and/or more comorbidity.

PMID- 24858013
TI  - Wet etching-assisted colloidal lithography: a general strategy toward nanodisk
      and nanohole arrays on arbitrary substrates.
AB  - A simple and facile strategy is presented to fabricate the metal nanodisk and
      nanohole arrays based on a wet etching-assisted polystyrene colloidal
      lithography. Gold is chosen to demonstrate the validity of such a strategy. The
      hexagonally arranged Au nanodisk and nanohole arrays are thus fabricated with
      large area and good uniformity. The structural parameters of the arrays, such as
      thicknesses, diameters, and spacings of the nanodisks or nanoholes, are facilely
      tunable and controllable by predeposition conditions, etching conditions and
      colloidal monolayer structure. More importantly, these arrays can be produced on
      any supporting substrates, such as conductive or nonconductive and even flexible
      substrates with flat, rough, or even curved surfaces. In general, the presented
      strategy is low in cost, simple in operation and arbitrary in substrate, and the
      as-prepared arrays could find potential devices' applications with nice
      compatibility in the fields of optics, surface-enhanced Raman spectroscopy,
      biosensing, and so forth. 

PMID- 24858012
TI  - Metformin induces apoptosis and cell cycle arrest mediated by oxidative stress,
      AMPK and FOXO3a in MCF-7 breast cancer cells.
AB  - Recent studies have demonstrated that the anti-diabetic drug, metformin, can
      exhibit direct antitumoral effects, or can indirectly decrease tumor
      proliferation by improving insulin sensitivity. Despite these recent advances,
      the underlying molecular mechanisms involved in decreasing tumor formation are
      not well understood. In this study, we examined the antiproliferative role and
      mechanism of action of metformin in MCF-7 cancer cells treated with 10 mM of
      metformin for 24, 48, and 72 hours. Using BrdU and the MTT assay, it was found
      that metformin demonstrated an antiproliferative effect in MCF-7 cells that
      occurred in a time- and concentration-dependent manner. Flow cytometry was used
      to analyze markers of cell cycle, apoptosis, necrosis and oxidative stress.
      Exposure to metformin induced cell cycle arrest in G0-G1 phase and increased cell
      apoptosis and necrosis, which were associated with increased oxidative stress.
      Gene and protein expression were determined in MCF-7 cells by real time RT-PCR
      and western blotting, respectively. In MCF-7 cells metformin decreased the
      activation of IRbeta, Akt and ERK1/2, increased p-AMPK, FOXO3a, p27, Bax and
      cleaved caspase-3, and decreased phosphorylation of p70S6K and Bcl-2 protein
      expression. Co-treatment with metformin and H2O2 increased oxidative stress which
      was associated with reduced cell number. In the presence of metformin, treating
      with SOD and catalase improved cell viability. Treatment with metformin resulted
      in an increase in p-p38 MAPK, catalase, MnSOD and Cu/Zn SOD protein expression.
      These results show that metformin has an antiproliferative effect associated with
      cell cycle arrest and apoptosis, which is mediated by oxidative stress, as well
      as AMPK and FOXO3a activation. Our study further reinforces the potential benefit
      of metformin in cancer treatment and provides novel mechanistic insight into its
      antiproliferative role.

PMID- 24858014
TI  - Low-temperature Raman fingerprints for few-quintuple layer topological insulator
      Bi2Se3 films epitaxied on GaAs.
AB  - Topological insulators (Bi2Se3) of single- and few-quintuple-layer (few-QLs)
      films were investigated by Raman spectroscopy and epitaxied on a GaAs substrate.
      At a measurement temperature of 80 K, we observed the emergence of additional A2u
      and Eu modes (Raman inactive in the bulk crystal) below 9-QLs film thicknesses,
      assigned to the crystal-symmetry breakdown in ultrathin films. Furthermore, the
      out-of-plane A1g modes changed in width, frequency, and intensity for decreasing
      numbers of QL, while the in-plane Eg mode split into three Raman lines, not
      resolved in previous room temperature experiments. The out-of-plane Raman modes
      showed a strong Raman resonance at 2.4 eV for around 4-QLs film thickness, and
      the resonant position of the same modes shifted to 2.2 eV for 18-QLs-thick film.
      The film thickness-dependence of the phonons frequencies cannot solely be
      explained within models of weak van der Waals interlayer coupling. The results
      are discussed in terms of stacking-induced changes in inter- and intralayer
      bonding and/or the presence of long-range Coulombic interlayer interactions in
      topological insulator Bi2Se3. This work demonstrates that Raman spectroscopy is
      sensitive to changes in film thickness over the critical range of 9- to 4-QLs,
      which coincides with the transition between a gapless topological insulator
      (occurring above 6-QLs) to a conventional gapped insulator (occurring below 4
      QLs).

PMID- 24858015
TI  - Cell banking for pharmaceutical research.
AB  - The provision of high-quality eukaryotic cells through robust cell banking
      processes is essential for the progression of drug discovery projects throughout
      the pharmaceutical research process. Numerous models exist to meet this aim, and
      this review describes many of the underlying principles, challenges and
      opportunities as well as detailing how these have been addressed within
      AstraZeneca. Crucial aspects discussed include cell line acquisition, cell bank
      generation, cryopreservation, storage, tracking and distribution. Because quality
      assurance underpins much of the process, quality control (QC) testing including
      mycoplasma screening and cell line authentication are also discussed in detail.
      Furthermore, because many of the underlying principles of cell banking are
      applicable in non-pharmaceutical settings, it is hoped that this review will
      prove a useful resource across the wider scientific community. 

PMID- 24858016
TI  - Corneal sensitivity in chronic inflammatory demyelinating polyneuropathy.
AB  - PURPOSE: Neurotrophic keratitis may result from a variety of ocular or systemic
      diseases. Chronic inflammatory demyelinating polyneuropathy (CIDP) is an
      autoimmune neuropathy that affects any nerve plexus but with no known association
      with corneal disease. We observed 2 patients with CIDP and visually compromising
      neurotrophic corneal ulcers. This study was performed to determine the prevalence
      of neurotrophic corneas in patients with CIDP to identify a subpopulation of
      asymptomatic patients who are at risk for vision loss. METHODS: This is an
      observational case series of 2 patients with CIDP with visually compromising
      neurotrophic corneal ulcers and a prospective clinical study comparing corneal
      sensitivity in 9 patients with CIDP versus 9 age- and sex-matched controls.
      Corneal sensitivity was tested with an esthesiometer. Statistical analyses were
      performed to determine patterns or significances in relation to the subject's
      age, gender, and duration and severity of the disease. RESULTS: The overall
      median corneal sensitivity was 5.7 for patients with CIDP and 6.0 for controls (P
      = 0.09). The mean corneal sensitivity was 5.6 +/- 0.4 in patients with CIDP
      compared with 5.8 +/- 0.3 in controls. No specific pattern was found with age,
      gender, or duration and severity of the disease among patients with CIDP.
      CONCLUSIONS: Although the case series demonstrated decreased corneal sensitivity
      in both patients with CIDP, the prospective study detected reduced corneal
      sensitivity in patients with CIDP when compared with controls, but did not reach
      statistical significance. Ophthalmic examinations with measurement of corneal
      sensitivity should be considered in the management of patients with CIDP.Clinical
      Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier:
      NCT01379833.

PMID- 24858017
TI  - Effect of diquafosol tetrasodium eye drop for persistent dry eye after laser in
      situ keratomileusis.
AB  - PURPOSE: To evaluate the effect of diquafosol tetrasodium (DQS) for the treatment
      of persistent dry eye after laser in situ keratomileusis (LASIK). SETTING: Miyata
      Eye Hospital, Miyazaki, Japan. DESIGN: Noncomparative case series. METHODS: This
      prospective study included 30 eyes of 15 patients in whom dry eye had persisted
      for over 12 months after LASIK, and the symptoms had not improved with artificial
      tears and sodium hyaluronate treatment. In addition, treatment with DQS 3% eye
      drops, 6 times a day, was performed for 12 weeks. Best-corrected visual acuity,
      tear secretion with the Schirmer test, tear break-up time, and fluorescein and
      lissamine green staining scores on the cornea and conjunctiva were examined
      before and at 1, 4, and 12 weeks after the addition. A subjective questionnaire
      of 14 symptoms was also assessed before and 12 weeks after treatment. RESULTS:
      The fluorescein and lissamine green staining scores significantly improved over
      12 weeks; however, the best-corrected visual acuity and tear secretion did not
      change. The symptoms of fatigue, dryness, grittiness, discomfort, difficulty in
      reading, and discomfort within the area of dryness improved after the additional
      DQS treatment. CONCLUSIONS: The DQS treatment improved the subjective and
      objective symptoms of persistent dry eye after LASIK. Increased mucin production
      because of the addition of DQS probably improved the tear film stability and
      reduced the symptoms of dry eye in patients who had persistent dry eye after
      LASIK.

PMID- 24858018
TI  - Neonatal infectious keratitis.
AB  - PURPOSE: The aim of this study was to determine predisposing factors, clinico
      microbiological profile, and outcomes of neonatal infectious keratitis. METHODS:
      The retrospective study included 39 eyes of 34 neonates treated for microbial
      keratitis at the L. V. Prasad Eye Institute, India, between January 2006 and
      December 2011. Etiologic microorganisms, predisposing factors, and management
      outcomes were evaluated. RESULTS: The Mean age at presentation was 16.9 + 7.7
      days, male:female = 16:18. The potential risk factors and coexisting conditions
      identified were prematurity and prolonged Neonatal Intensive Care Unit (NICU)
      care, route of delivery, maternal infections, systemic associations, and ocular
      malformations. Microbiology workup yielded positive results in 29 eyes. Ten eyes
      were smear and culture negative, with results of immunofluorescent assay and
      polymerase chain reaction for herpes simplex virus being negative. Bacteria were
      the commonest (23/39 eyes, 59%) cause of infections, and Pseudomonas aeruginosa
      was the commonest (12/23 eyes, 52%) bacterial isolate. Multidrug-resistant
      Pseudomonas keratitis was identified in 8/12 (67%) eyes. Keratitis resolved on
      medical treatment in 34 eyes. Two of these eyes with scars underwent penetrating
      keratoplasty later. Of the 8 eyes with multidrug-resistant P. aeruginosa
      keratitis, 3 eyes had near-total corneal infiltrates, 2 eyes developed anterior
      staphyloma, 1 eye autoeviscerated, and 1 eye required a therapeutic tectonic
      graft. One of the 2 eyes with fungal keratitis underwent therapeutic penetrating
      keratoplasty. CONCLUSIONS: Identification of the appropriate predisposing
      factors, etiologic microbial organisms, and treatment outcome from this study may
      aid in early recognition and treatment of microbial keratitis in neonates.

PMID- 24858019
TI  - Correlation of corneal endothelial changes with different stages of keratoconus.
AB  - PURPOSE: The aim was to study the corneal endothelial count and morphology in
      patients with keratoconus by specular microscopy and to correlate them to the
      stage of keratoconus. METHODS: Forty eyes of 29 patients with keratoconus were
      enrolled in this cross-sectional cohort study. Corneal endothelium was evaluated
      using specular microscopy, and corneal topography and thickness data were
      obtained from Scheimpflug-based corneal tomography. Eyes were classified into
      stages 1 through 4 of keratoconus according to Amsler classification, using
      keratometry and pachymetry readings obtained from corneal tomography. RESULTS:
      Eleven eyes (27.5%) had stage 1, 17 eyes (42.5%) had stage 2, and 12 eyes (30%)
      had stage 3. Specular microscopy was not possible in stage 4. There was no
      statistically significant correlation between the stage of keratoconus and the
      endothelial cell density (ECD) (r = 0.018, P = 0.91), coefficient of variation
      (CV) (r = -0.011, P = 0.94), or percentage of hexagonality (6A) (r = -0.112, P =
      0.51). When mild-to-moderate keratoconus (stages 1 and 2) was compared with
      severe keratoconus (stage 3), the difference was not significant regarding ECD (P
      = 0.1), CV (P = 0.3), or 6A (P = 0.4). However, there was a trend toward lower
      ECD and percentage of hexagonality, and a higher CV with advancing disease.
      CONCLUSIONS: Up to stage 3, keratoconus does not significantly affect the corneal
      endothelium, as measured by specular microscopy. Eyes with stage 4 could not be
      studied by specular microscopy and may require other imaging methods such as
      confocal microscopy.

PMID- 24858020
TI  - Successful treatment of Paecilomyces lilacinus keratitis with oral posaconazole.
AB  - PURPOSE: To report a case of successful medical treatment with oral posaconazole
      in refractory fungal keratitis caused by Paecilomyces lilacinus. METHODS: Case
      report. RESULTS: A 57-year-old male, soft contact lens wearer presented with
      irritation, pain, photophobia, and reduced vision. Slit-lamp examination showed a
      large corneal epithelial defect with a peripheral infiltrate. The patient did not
      improve on fortified topical antibiotics. After the diagnosis of P. lilacinus
      fungal keratitis, oral voriconazole and topical antifungal therapy were started.
      Despite antifungal therapy, progressive disease required therapeutic penetrating
      keratoplasty. Postoperatively, because of clinical signs of recurrence and in
      vivo confocal microscopy findings of presumed hyphae in the cornea, intracameral
      miconazole was injected and oral posaconazole was started. The patient improved
      and demonstrated no hyphae 6 weeks after starting posaconazole. When posaconazole
      was stopped, the cornea remained clear with excellent acuity. However, because of
      acute graft rejection 2 months after stopping posaconazole, keratoprosthesis was
      implanted, with no evidence of infection at surgery or during the 3.5-year follow
      up. CONCLUSIONS: To the best of our knowledge, this is the first report on the
      use of oral posaconazole for Paecilomyces keratitis. Posaconazole might be
      indicated in the treatment of refractory Paecilomyces keratitis that is resistant
      to conventional therapy.

PMID- 24858021
TI  - Pterygium is related to a decrease in corneal endothelial cell density.
AB  - PURPOSE: The aim of this study was to investigate the relationship between
      pterygium and a decrease in the corneal endothelial cell density (ECD) in
      patients with unilateral primary pterygium. METHODS: In this retrospective cross
      sectional study, 90 consecutive patients with unilateral primary pterygium were
      enrolled from January 2010 to June 2012. Corneal ECD was measured in both eyes,
      and the fellow eyes were considered as controls. The relationship between the
      percentage of pterygium to cornea and a decrease in the ECD was analyzed. An
      increase in astigmatism in eyes with pterygium was evaluated for association with
      decreased ECD using the Pearson correlation test. RESULTS: The percentage of
      pterygium to cornea ranged from 3.5% to 65.2%, with a median of 12.35%. The
      difference in the corneal ECD between eyes with pterygium and control eyes ranged
      from +9.6% to -37.7%, with a median of -9.75%. The results of the Pearson
      correlation statistical test showed a strong logarithmic correlation between a
      decrease in the corneal ECD and the percentage of pterygium to cornea (R = 0.688,
      P < 0.001). An increase in astigmatism was correlated with a decrease in the ECD
      in eyes with pterygium. CONCLUSIONS: Pterygium is related to a decrease in
      corneal ECD. Surgical intervention should be considered in patients with
      extensive pterygium involvement in the cornea or a significant increase in
      astigmatism.

PMID- 24858022
TI  - Tear film osmolarity in ocular mucous membrane pemphigoid.
AB  - PURPOSE: The aim of this study was to evaluate tear film osmolarity in patients
      with ocular mucous membrane pemphigoid (MMP). METHODS: This observational cross
      sectional study included 40 patients with biopsy-proven ocular MMP at Foster
      stage III referred to the tertiary-care Ocular Immunology and Uveitis Service at
      the San Raffaele Scientific Institute in Milan from June 2010 to August 2013. We
      evaluated the following clinical parameters: tear film osmolarity, ocular surface
      disease symptoms (OSDI) questionnaire, Schirmer test, tear film break-up time
      (TFBUT), and corneal and conjunctival staining. RESULTS: Forty patients (27 women
      and 13 men) were enrolled. All patients were undergoing systemic
      immunosuppressive therapy: 19 patients (47.5%) were on methotrexate, 9 (22.5%)
      were on mycophenolate mofetil, 9 (22.5%) were on low-dose corticosteroids, and 3
      (7.5%) were on azathioprine. The mean osmolarity was 322.90 +/- 33.39 mOsm/L, the
      mean OSDI score was 73.2 +/- 17.9, the mean TFBUT was 6.60 +/- 3.13 seconds, and
      the mean Schirmer test value was 4.07 +/- 3.58 seconds. Tear film osmolarity
      significantly correlated with the TFBUT (r = 0.80; P < 0.0001), whereas no
      clinical correlation was found with the Schirmer test value (r = 0.01; P = 0.40)
      or with the OSDI score (r = 0.02; P = 0.29). Osmolarity did not turn out to be
      statistically different in the subgroups according to the Oxford corneal staining
      scale (P = 0.71) and to the Van Bijsterveld conjunctival staining score (P =
      0.31). CONCLUSIONS: Tear osmolarity increased in patients with ocular MMP and
      correlated with the TFBUT. This result emphasizes the role of evaporative dry-eye
      condition in patients with ocular MMP. Tear osmolarity may be considered as a
      useful test in the diagnostic assessment of dry eye associated with MMP and for
      targeting therapeutic decisions.

PMID- 24858023
TI  - HLA-DR9 and DR14 are associated with the allopurinol-induced hypersensitivity in
      hematologic malignancy.
AB  - Allopurinol, a widely used urate-lowering agent, is a leading cause of severe
      cutaneous adverse reactions (SCARs), especially in patients with HLA-B*58:01.
      Despite its routine use for the prevention of tumor lysis-related hyperuricemia
      prior to chemotherapy, the risk of allopurinol-induced hypersensitivity has not
      been investigated in patients with hematologic malignancies. This retrospective
      cohort study was conducted to investigate the incidence and risk factors of
      allopurinol-induced hypersensitivity in patients at least 18 years of age with
      hematologic malignancies. We reviewed 463 patients who had ever taken allopurinol
      for the prevention of hyperuricemia prior to chemotherapy and had undergone
      serologic HLA typing as a pre-transplant evaluation from January 2000 to May
      2010. Thirteen (2.8%) patients experienced maculopapular eruptions (MPE) and none
      experienced SCARs. Among subtypes of underlying hematologic malignancies,
      percentage of chronic myeloid leukemia was significantly higher in the
      allopurinol hypersensitivity group compared with the tolerant group (23.1% (3/13)
      vs. 5.9% (26/440), P = 0.044). According to HLA subtypes, the incidence of
      allopurinol-induced MPE was 4.0% in HLA-B58 (+) patients (2/50) and 2.7% in HLA
      B58 (-) patients (11/403) but this difference was statistically insignificant. In
      contrast to HLA-B58, the frequencies of DR9 and DR14 were significantly higher in
      the allopurinol-induced MPE group compared with the allopurinol tolerant group
      (38.5% (5/13) vs. 13.6% (53/443), P = 0.019, and 38.5% (5/13) vs. 15.6% (41/440),
      P = 0.038, respectively). In conclusion, HLA-DR9 and DR14, but not HLA-B58, are
      associated with hypersensitivity reaction by allopurinol when administered in
      patients with hematologic malignancy prior to chemotherapy. 

PMID- 24858024
TI  - Tetraspanin-enriched microdomains and hepatocellular carcinoma progression.
AB  - As in many tumors, heterogeneity within the cell population is one of the main
      features of hepatocellular carcinoma (HCC). Heterogeneity results from the
      ability of tumor to produce multiple subpopulations of cells with diverse
      genetic, biochemical and immunological characteristics. Little is known about how
      heterogeneity emerges and how it is maintained. Fluctuations in single cells can
      be masked or completely misrepresented when cell populations are analyzed. It has
      become exceedingly apparent that the utility of measurement based on the analysis
      of bulk specimens is limited by intra-tumor genetic and epigenetic heterogeneity,
      as characteristics of the most abundant cell type might not necessarily predict
      the properties of cell populations. Yet, such non-uniformities often unveil
      molecular patterns that can represent mechanisms of tumor progression.
      Interestingly, variability among single cells in a population may arise from
      different responses to intrinsic and extrinsic perturbations mainly mediated by
      the plasma membrane. The association of certain proteins, including tetraspanins,
      and lipids in specific location on the plasma membrane constitutes specialized
      structure called tetraspanin-enriched microdomains (TEMs). TEMs organization in
      cancer may reveal essential clues for understanding pathogenic mechanisms
      underlying cancer progression. Along these lines, TEMs and HCC progression
      represent a valuable paradigm for gaining a deeper understanding of such
      mechanisms. 

PMID- 24858025
TI  - Sodium orthovanadate inhibits growth of human hepatocellular carcinoma cells in
      vitro and in an orthotopic model in vivo.
AB  - The transition metal vanadium is widely distributed in the environment and
      exhibits various biological and physiological effects in the human body. As a
      well known vanadium compound, sodium orthovanadate (SOV) has shown promising
      antineoplastic activity in several human cancers. However, the effects of SOV on
      liver cancer are still unknown. In this study, for the first time, we showed that
      SOV could effectively suppress proliferation, induce G2/M cell cycle arrest and
      apoptosis, and diminish the mitochondrial membrane potential (MMP) of HCC cells
      in vitro. In addition, our in vitro results were recapitulated in vivo, showing
      that SOV exhibited a dose-dependent inhibition of growth of human HCC in an
      orthotopic model, evidenced by the reduction in tumor size, proliferation index
      and microvessel density, and increase in cell apoptosis. Most important, we found
      that SOV could inhibit autophagy in HCC cells in vitro and in vivo, which plays a
      prodeath role. Thus, our findings suggest that SOV could effectively suppress the
      growth of human HCC through the regulations of proliferation, cell cycle,
      apoptosis and autophagy, and thus may act as a potential therapeutic agent in HCC
      treatment. 

PMID- 24858026
TI  - Epigenetic silencing of BTB and CNC homology 2 and concerted promoter CpG
      methylation in gastric cancer.
AB  - BTB and CNC homology 2 (BACH2) is a lymphoid-specific transcription factor with a
      prominent role in B-cell development. Genetic polymorphisms within a single locus
      encoding BACH2 are associated with various autoimmune diseases and allergies. In
      this study, restriction landmark genomic scanning revealed methylation at a NotI
      site in a CpG island covering the BACH2 promoter in gastric cancer cell lines and
      primary gastric tumors. Increased methylation of the BACH2 promoter was observed
      in 52% (43/83) of primary gastric tumors, and BACH2 hypermethylation was
      significantly associated with decreased gene expression. Treatment with 5-aza-2'
      deoxycytidine and/or trichostatin. A restored BACH2 expression in BACH2-silenced
      gastric cancer cell lines, and knockdown of BACH2 using short hairpin RNA (i.e.
      RNA interference) increased cell proliferation in gastric cancer cells.
      Clinicopathologic data showed that decreased BACH2 expression occurred
      significantly more frequently in intestinal-type (27/44, 61%) compared with
      diffuse-type (13/50, 26%) gastric cancers (P<0.001). Furthermore, BACH2 promoter
      methylation paralleled that of previously identified targets, such as LRRC3B,
      LIMS2, PRKD1 and POPDC3, in a given set of gastric tumors. We propose that
      concerted methylation in many promoters plays a role in accelerating gastric
      tumor formation and that methylated promoter loci may be targets for therapeutic
      treatment, such as the recently introduced technique of epigenetic editing. 

PMID- 24858027
TI  - Maternal immune transfer in mollusc.
AB  - Maternal immunity refers to the immunity transferred from mother to offspring via
      egg, playing an important role in protecting the offspring at early life stages
      and contributing a trans-generational effect on offspring's phenotype. Because
      fertilization is external in most of the molluscs, oocytes and early embryos are
      directly exposed to pathogens in the seawater, and thus maternal immunity could
      provide a better protection before full maturation of their immunological
      systems. Several innate immune factors including pattern recognition receptors
      (PRRs) like lectins, and immune effectors like lysozyme, lipopolysaccharide
      binding protein/bacterial permeability-increasing proteins (LBP/BPI) and
      antioxidant enzymes have been identified as maternally derived immune factors in
      mollusc eggs. Among these immune factors, some maternally derived lectins and
      antibacterial factors have been proved to endue mollusc eggs with effective
      defense ability against pathogen infection, while the roles of other factors
      still remain untested. The physiological condition of mollusc broodstock has a
      profound effect on their offspring fitness. Many other factors such as nutrients,
      pathogens, environment conditions and pollutants could exert considerable
      influence on the maternal transfer of immunity. The parent molluscs which have
      encountered an immune stimulation endow their offspring with a trans-generational
      immune capability to protect them against infections effectively. The knowledge
      on maternal transfer of immunity and the trans-generational immune effect could
      provide us with an ideal management strategy of mollusc broodstock to improve the
      immunity of offspring and to establish a disease-resistant family for a long-term
      improvement of cultured stocks. 

PMID- 24858028
TI  - A novel lineage transcription factor based analysis reveals differences in T
      helper cell subpopulation development in infected and intrauterine growth
      restricted (IUGR) piglets.
AB  - Research in mouse and human clearly identified subsets of T helper (Th) cells
      based on nuclear expression of specific lineage transcription factors. In swine,
      however, transcription factor based detection of functional subpopulations of
      porcine Th cells by flow cytometry is so far limited to regulatory T cells via
      Foxp3. T-bet and GATA-3 are the transcription factors that regulate commitment to
      Th1 or Th2 cells, respectively. In this study we prove GATA-3 and T-bet
      expression in porcine CD4(+) cells polarized in vitro. Importantly, GATA-3 and T
      bet expressing cells were detectable in pigs infected with pathogens associated
      with Th2 and Th1 immune responses. Increased frequencies of GATA-3 positive
      CD4(+) cells are found in vivo in pigs experimentally infected with the nematode
      Trichuris suis, whereas porcine reproductive and respiratory syndrome virus
      (PRRSV) infection elicited T-bet positive CD4(+) T cells. Analysing the immune
      status of pre-weaning piglets with intrauterine growth restriction (IUGR) we
      found an increased expression of Foxp3, T-bet and GATA-3 in CD4(+) and
      CD4(+)CD8(+) double-positive T cells in systemic and intestinal compartments of
      IUGR piglets. Hence, we established the detection of porcine Th1 and Th2 cells
      via T-bet and GATA-3 and show that the porcine lineage transcription factors are
      differentially regulated very early in life depending on the developmental
      status. 

PMID- 24858029
TI  - Expression pattern of Toll-like receptors (TLRs) in different organs and effects
      of lipopolysaccharide on the expression of TLR 2 and 4 in reproductive organs of
      female rabbit.
AB  - Toll-like receptors (TLRs) are vital for innate immunity, and they were expressed
      in various immune cells, tissues and organs. Moreover, TLRs specific expression
      pattern in different cells, tissue and organs have been confirmed to have
      correlation with the ability to resistance to pathogenic challenges. The present
      study aimed to determine the expression profiles and levels of TLR2, 3, 4, 5, 6,
      8 and 10 in the lung, trachea, intestine, stomach, liver, spleen, uterine horn
      and body, cervix, ovary, oviduct and hypothalamus of female rabbits, and whether
      the expression level of TLR2 and 4 in the ovary, oviduct, uterine horn and body,
      and cervix were affected by lipopolyasaccharide (LPS). The tissues of the lung,
      trachea, intestine, stomach, liver, spleen, uterine horn and body, cervix, ovary,
      oviduct and hypothalamus were collected from four rabbits which didn't be treated
      as 0 h. 16 rabbits in LPS group were injected with LPS (according to 0.5mg/kg
      body weight) and 16 rabbits in control group were injected with saline (LPS
      carrier), hereafter the tissues of the uterine horn and body, cervix, ovary and
      oviduct from 32 rabbits were collected after 1.5, 3, 6, and 12h (n=4 each group)
      postinjection. The expression profiles of TLRs were analyzed by reverse
      transcriptase polymerase chain reaction (RT-PCR), and expression level of TLRs
      were examined using quantitative real-time PCR (qRT-PCR). The results shown:
      TLR2, 3, 4, 5, 6, 8 and 10 were expressed in lung, trachea, intestine, stomach,
      liver, spleen, uterine horn and body, cervix, ovary, oviduct and hypothalamus of
      female rabbits, but their expression level had great difference in the same
      organs, and each TLR has different expression level in the different organs.
      After LPS-stimulation, the expression of TLR2 in the uterine body and horn was
      significantly higher than that in control group by 3h and 12h of postinjection
      (P<0.05) respectively. The expression of TLR4 in ovary and uterine body was
      significantly higher than that in control group by 3 and 12h of postinjection
      (P<0.05), and the expression of TLR4 in uterine body was greater than that in
      control by 3h postinjection (P<0.05). The results suggested LPS upregulated the
      expression of TLR2 and 4 in uterine body and horn, and the expression of TLR4 in
      ovary.

PMID- 24858030
TI  - Expression and protective role of two novel NACHT-containing proteins in pathogen
      infection.
AB  - Lower vertebrates have been found to possess over 200 NACHT-domain encoding
      genes; but, to date, very little is known about their functional activity. This
      article describes the sequences and expression analysis of two zebrafish NACHT
      containing proteins, namely NALPL1 and NALPL2. In addition, the functions of
      zebrafish NALPL1 and NALPL2, which are absent for both amino-terminal effector
      binding domain (EBD) and carboxy-terminal ligand-recognition domain (LRD), were
      investigated for the first time in fish species. The predicted NALPL1 and NALPL2
      proteins consist of 651 and 847 amino acids (aa), respectively, with both
      molecules only containing NACHT domain, which were different from other NACHT
      family members. Phylogenetic analysis showed that zebrafish NALPL1 and NALPL2
      have a closer relationship with mammalian NALP subfamily than NOD subfamily. The
      differential expression patterns of NALPL1 and NALPL2 in development stages and
      organs were observed, suggesting the difference of action phase and effector
      organ of NALPL1 and NALPL2. When the modulation of NALPL1 and NALPL2 in pathogen
      infection was analyzed, it was found that the two molecules were upregulated by
      both bacterial and viral infection. Overexpression of NALPL1 and NALPL2 resulted
      in significant inhibition for intracellular Edwardsiella tarda growth. Further
      studies demonstrated that NALPL1 and NALPL2 also contributed to protection
      against viral infection. These results demonstrate that both NALPL1 and NALPL2
      are important intracellular proteins in host surveillance against both bacterial
      and viral infection. Interestingly, the expression of downstream signaling genes
      was not affected by the overexpression of NALPL1 or NALPL2, but NOD1 and MDA5
      were upregulated by NALPL1 or NALPL2 overexpression, suggesting that they likely
      act in pathogen infection through the interaction with other PRRs. 

PMID- 24858031
TI  - Calnexin functions in antibacterial immunity of Marsupenaeus japonicus.
AB  - Calnexin (Cnx) is an endoplasmic reticulum membrane-bound lectin chaperone that
      comprises a dedicated maturation system with another lectin chaperone
      calreticulin (Crt). This maturation system is known as the Cnx/Crt cycle. The
      main functions of Cnx are Ca(2+) storage, glycoprotein folding, and quality
      control of synthesis. Recent studies have shown that Cnx is important in
      phagocytosis and in optimizing dendritic cell immunity. However, the functions of
      Cnx in invertebrate innate immunity remain unclear. In this research, we
      characterized Cnx in the kuruma shrimp Marsupenaeus japonicus (designated as
      MjCnx) and detected its function in shrimp immunity. The expression of MjCnx was
      upregulated in several tissues challenged with Vibrio anguillarum. Recombinant
      MjCnx could bind to bacteria by binding polysaccharides. MjCnx protein existed in
      the cytoplasm and on the membrane of hemocytes and was upregulated by bacterial
      challenge. The recombinant MjCnx enhanced the clearance of V. anguillarum in
      vivo, and the clearance effects were impaired after silencing MjCnx with RNA
      interference assay. Recombinant MjCnx promoted phagocytosis efficiency of
      hemocytes. These results suggest that MjCnx functions as one of the pattern
      recognition receptors and has crucial functions in shrimp antibacterial immunity.

PMID- 24858033
TI  - Three-dimensional chemical imaging of skin using stimulated Raman scattering
      microscopy.
AB  - Stimulated Raman scattering (SRS) microscopy is used to generate structural and
      chemical three-dimensional images of native skin. We employed SRS microscopy to
      investigate the microanatomical features of skin and penetration of topically
      applied materials. Image depth stacks are collected at distinct wavelengths
      corresponding to vibrational modes of proteins, lipids, and water in the skin. We
      observed that corneocytes in stratum corneum are grouped together in clusters,
      100 to 250 MUm in diameter, separated by 10- to 25-MUm-wide microanatomical skin
      folds called canyons. These canyons occasionally extend down to depths comparable
      to that of the dermal-epidermal junction below the flat surface regions in
      porcine and human skin. SRS imaging shows the distribution of chemical species
      within cell clusters and canyons. Water is predominately located within the cell
      clusters, and its concentration rapidly increases at the transition from stratum
      corneum to viable epidermis. Canyons do not contain detectable levels of water
      and are rich in lipid material. Oleic acid-d34 applied to the skin surface lines
      the canyons down to a depth of 50 MUm below the surface of the skin. This
      observation could have implications on the evaluation of penetration profiles of
      bioactive materials measured using traditional methods, such as tape-stripping.

PMID- 24858035
TI  - Protective role of C-phycocyanin against secondary changes during sodium selenite
      mediated cataractogenesis.
AB  - Age related cataract is the leading cause of blindness associated with
      accumulation of oxidative stress in the eye lens. The present investigation
      reveals the rational of the beneficial effects of the natural compound C
      phycocyanin (C-PC) is beneficial when administered to rat pups to protect against
      the secondary effects of sodium selenite induced cataractogenesis. A single
      subcutaneous dose of sodium selenite (19 MUmol/kg body weight) on the 10th day of
      postpartum is adequate to induce cataract in rat pups. Serum biochemical
      parameters, such as the level of electrolytes, mean activities of anti-oxidant
      enzymes i.e. superoxide dismutase, catalase and reduced glutathione were observed
      to be significantly altered during selenite induced cataractogenic process.
      Histopathological examination revealed signs of degradation of normal cell
      architecture in the liver, kidney and eye lens. Interestingly, the deleterious
      effects of sodium selenite toxicity were restored with the simultaneous treatment
      with C-PC. The results suggest that an administration of 200 mg/kg body weight of
      C-PC has the ability to prevent/alter the secondary changes reflected in the
      serum biochemical and histological modifications in rats exposed to sodium
      selenite. These results complement the beneficial role of C-PC of cyanobacterial
      origin as a efficacious anti-cataractogenic agent against sodium selenite
      toxicity. 

PMID- 24858036
TI  - Loss of autonomy of hospitalized elderly patients: does hospitalization increase
      disability?
AB  - AIM: The study of the determinants of loss of autonomy during hospitalization may
      be valuable in the identification of the most effective interventions and to
      achieve better outcomes. The aim of this study was to describe changes in the
      level of autonomy of the elderly admitted to the hospital at the entrance and at
      discharge in relation to a rehabilitation program. METHODS: Prospective
      observational study conducted at the INRCA Geriatric Hospital of Ancona. The
      study included patients aged 65 years and over, daily admitted to INRCA Hospital
      of Ancona between September and December 2010. Criteria for inclusion were age >=
      65 years, length of stay > 24 hours and signed informed consent. Patients
      admitted for less than 24 hours or in day hospital or day surgery were excluded
      from the beginning. A total of 1266 elderly patients were recruited in the
      period. From this sample, 74 people who died during hospitalization were
      excluded. At the time of hospitalization (within 24 hours) and at discharge,
      patients were evaluated with the Barthel Index (BI), the Rankin scale, and a
      short assessment of cognitive status derived from the Mini Mental State
      Examination (MMSE). RESULTS: Referring to 1192 subjects who participated to the
      study, the mean age was 82.13 years +/-7.39, age range between 65 and 100 years.
      The average BI was 56.6+/-36.16 (SD) (median value =60) at admission and 63.84+/
      34.7 (SD) (median value=70) at discharge. The average Rankin score at admission
      was 2.63+/-1.5 (SD) (median value=3). CONCLUSION: Patients presented better score
      of the BI at discharge and this figure was associated to the implementation of a
      rehabilitation treatment. Hospitalization of the elderly patient in a suitable
      environment, such as a geriatric hospital, contrary to some theories highlighting
      only the negative aspects of removal from the living environment, can be a
      measure of benefit for the reduction of disability and the recovery of
      compromised activities along and after the acute event. The collection of data on
      the level of autonomy of the subjects before and after hospitalization can be a
      useful element for clinical evaluation in a geriatric hospital.

PMID- 24858037
TI  - Loss of presenilin 2 is associated with increased iPLA2 activity and lung tumor
      development.
AB  - Presenilins are the enzymatic components of gamma-secretase complex that cleaves
      amyloid precursor protein, Notch and beta-catenin, which has critical roles in
      the development of Alzheimer's disease and cancer cell growth. Therefore, in the
      present study, we studied the effects and mechanisms of PS2 knockout on lung
      cancer development and possible mechanisms as a key regulator of lung tumor
      development. We compared carcinogen-induced tumor growth between PS2 knockout
      mice and wild-type mice. PS2 knockout mice showed increased urethane (1 mg/g)
      induced lung tumor incidence when compared with that of wild-type mice with
      decreased activity of gamma-secretase in the lung tumor tissues. Consequently,
      iPLA2 activities in lung tumor tissues of PS2 knockout mice were much higher than
      in tumor tissues of wild-type mice. Furthermore, knockdown of PS2 using PS2 siRNA
      decreased gamma-secretase activity with increased iPLA2 activity in the lung
      cancer cells (A549 and NCI-H460), leading to increased lung cancer cell growth.
      PS2 knockout mice and PS2 knockdown lung cancer cells showed increased DNA
      binding activities of nuclear factor kappa-beta, signal transducer and activator
      of transcription 3 (STAT3) and AP-1 which are critical transcriptional factors of
      iPLA2 than those of PS2 wild-type mice and control lung cancer cells. Taken
      together, these results suggest that the loss of PS2 could have a critical role
      in lung tumor development through the upregulation of iPLA2 activity by reducing
      gamma-secretase.

PMID- 24858038
TI  - Cks overexpression enhances chemotherapeutic efficacy by overriding DNA damage
      checkpoints.
AB  - Cdc kinase subunit (Cks) proteins Cks1 and Cks2 are adaptor-like proteins that
      bind many cyclin-dependent kinases. A wealth of clinical data has shown that Cks
      proteins are overexpressed in many types of human cancers and this often
      correlates with increased tumor aggressiveness. Previously, we showed that Cks
      overexpression abrogates the intra-S-phase checkpoint, a major barrier to
      oncogene-mediated transformation. Interestingly, the intra-S-phase checkpoint is
      crucial for the cellular response to replication stress, a major pathway of
      apoptosis induction by many chemotherapeutic agents. Here, we demonstrate cancer
      cells that overexpress Cks1 or Cks2 override the intra-S-phase checkpoint in the
      presence of replication stress-inducing chemotherapies such as 5-Fluorouracil (5
      FU) and methotrexate (MTX) leading to enhanced sensitivity in vitro and in vivo.
      Furthermore, enforced expression of Cks1 in an MTX-resistant breast cancer cell
      line was found to restore drug sensitivity. Our results suggest that Cks proteins
      are important determinants of apoptosis induction of replication stress-inducing
      chemotherapies such as 5-FU.

PMID- 24858040
TI  - The uric acid transporter SLC2A9 is a direct target gene of the tumor suppressor
      p53 contributing to antioxidant defense.
AB  - Only humans and higher primates have high uric acid blood levels. Although high
      uric acid causes gout, it has been linked with human longevity because of its
      hypothetical antioxidant function. Recent studies reveal that p53 has significant
      roles in cellular metabolism. One example of this is an antioxidant function that
      potentially contributes to tumor suppression. Here, we reported a first
      beneficial link between p53 and uric acid. We identified the uric acid
      transporter SLC2A9 (also known as GLUT9) as a direct p53 target gene and a key
      downstream effector in the reduction of reactive oxygen species (ROS) through
      transporting uric acid as a source of antioxidant. Oxidative stress induced
      SLC2A9 expression in a p53-dependent manner, and inhibition of SLC2A9 by small
      interfering RNA (siRNA) or anti-gout drugs such as probenecid significantly
      increased ROS levels in an uric acid-dependent manner and greatly sensitized
      cancer cells to chemotherapeutic drugs. Conversely, expression of SLC2A9 reduced
      ROS and protected against DNA damage and cell death, suggesting its antioxidant
      function. The increased production of ROS because of p53 loss was rescued by
      SLC2A9 expression. Furthermore, decreased SLC2A9 expression was observed in
      several cancer types and was associated with a poorer prognosis. Our findings
      suggest that the p53-SLC2A9 pathway is a novel antioxidant mechanism that uses
      uric acid to maintain ROS homeostasis and prevent accumulation of ROS-associated
      damage that potentially contributes to cancer development.

PMID- 24858039
TI  - Vimentin regulates lung cancer cell adhesion through a VAV2-Rac1 pathway to
      control focal adhesion kinase activity.
AB  - Vimentin is an intermediate filament protein whose expression correlates with
      increased metastatic disease, reduced patient survival and poor prognosis across
      multiple tumor types. Despite these well-characterized correlations, the
      molecular role of vimentin in cancer cell motility remains undefined. To approach
      this, we used an unbiased phosphoproteomics screen in lung cancer cell lines to
      discover cell motility proteins that show significant changes in phosphorylation
      upon vimentin depletion. We identified the guanine nucleotide exchange factor
      (GEF), VAV2, as having the greatest loss of phosphorylation owing to vimentin
      depletion. Since VAV2 serves as a GEF for the small Rho GTPase Rac1, a key player
      in cell motility and adhesion, we explored the vimentin-VAV2 pathway as a
      potential novel regulator of lung cancer cell motility. We show that VAV2
      localizes to vimentin-positive focal adhesions (FAs) in lung cancer cells and
      complexes with vimentin and FA kinase (FAK). Vimentin loss impairs both pY142
      VAV2 and downstream pY397-FAK activity showing that vimentin is critical for
      maintaining VAV2 and FAK activity. Importantly, vimentin depletion reduces the
      activity of the VAV2 target, Rac1, and a constitutively active Rac1 rescues
      defects in FAK and cell adhesion when vimentin or VAV2 is compromised. Based upon
      this data, we propose a model whereby vimentin promotes FAK stabilization through
      VAV2-mediated Rac1 activation. This model may explain why vimentin expressing
      metastatic lung cancer cells are more motile and invasive.

PMID- 24858041
TI  - A cadherin switch underlies malignancy in high-grade gliomas.
AB  - Although the infiltrative behavior of malignant gliomas is one of their most
      critical aspects, the mechanisms underlying it have not yet been elucidated. To
      migrate in the brain parenchyma, malignant glioma cells need to bypass the cell
      cell contact inhibitory signals. Here we propose that the blinding of cell-cell
      contact sensing in gliomas is caused by an unusual mechanism of cadherin switch,
      involving the replacement of N-cadherin with R-cadherin (Rcad) at the cell-cell
      junctions and the activation of ERK and p27. In our model of malignant glioma, we
      found that Rcad expression is necessary and sufficient to release cells from
      contact inhibition of proliferation, and is necessary, although not sufficient,
      for overriding contact inhibition of migration and for tumorigenicity.
      Altogether, these observations suggest that Rcad is a potential target for
      malignant glioma therapies.

PMID- 24858042
TI  - Epithelial-mesenchymal status renders differential responses to cisplatin in
      ovarian cancer.
AB  - Chemoresistance to platinums, such as cisplatin, is of critical concern in the
      treatment of ovarian cancer. Recent evidence has linked epithelial-mesenchymal
      transition (EMT) as a contributing mechanism. The current study explored the
      connection between cellular responses to cisplatin and EMT in ovarian cancer.
      Expression microarrays were utilized to estimate the EMT status as a binary
      phenotype, and the transcriptional responses of 46 ovarian cancer cell lines to
      cisplatin were measured at dosages equivalent to 50% growth inhibition.
      Phenotypic responses to cisplatin were quantified with respect to cell number,
      proliferation rate and apoptosis, and then compared with the epithelial or
      mesenchymal status. Ovarian cancer cell lines with an epithelial status exhibited
      higher resistance to cisplatin treatment in the MTS assay than those with a
      mesenchymal status. Pathway analyses revealed the induction of G1/S- and S-phase
      genes (P=0.001) and the activation of multiple NF-kappaB (nuclear factor kappa
      light-chain-enhancer of activated B cells) downstream genes (P=0.0016) by
      cisplatin selectively in epithelial-like cell lines. BrdU incorporation and
      Caspase-3/7 release assays confirmed impaired apoptosis in epithelial-like
      ovarian cancer cells. In clinical samples, we observed resistance to single
      platinum treatment and the selective activation of the NF-kappaB pathway by
      platinum in ovarian cancers with an epithelial status. Overall, our results
      suggest that, in epithelial-like ovarian cancer cells, NF-kappaB activation by
      cisplatin may lead to defective apoptosis, preferential proliferation arrest and
      a consequential decreased sensitivity to cisplatin.

PMID- 24858043
TI  - MCT-1 expression and PTEN deficiency synergistically promote neoplastic
      multinucleation through the Src/p190B signaling activation.
AB  - Multinucleation is associated with malignant neoplasms; however, the molecular
      mechanism underlying the nuclear abnormality remains unclear. Loss or mutation of
      PTEN promotes the development of malignant tumors. We now demonstrate that
      increased expression of the oncogene MCT-1 (multiple copies in T-cell malignancy
      1) antagonizes PTEN gene presentation, PTEN protein stability and PTEN functional
      activity, thereby further promoting phosphoinositide 3 kinase/AKT signaling,
      survival rate and malignancies of the PTEN-deficient cells. In the PTEN-null
      cancer cells, MCT-1 interacts with p190B and Src in vivo, supporting that they
      are in proximity of the signaling complexes. MCT-1 overexpression and PTEN loss
      synergistically augments the Src/p190B signaling function that leads to
      inhibition of RhoA activity. Under such a condition, the incidence of mitotic
      catastrophes including spindle multipolarity and cytokinesis failure is enhanced,
      driving an Src/p190B/RhoA-dependent neoplastic multinucleation. Targeting MCT-1
      by the short hairpin RNA markedly represses the Src/p190B function, improves
      nuclear structures and suppresses xenograft tumorigenicity of the PTEN-null
      breast cancer cells. Consistent with the oncogenic effects in vitro, clinical
      evidence has confirmed that MCT-1 gene stimulation is correlated with p190B gene
      promotion and PTEN gene suppression in human breast cancer. Accordingly, MCT-1
      gene induction is recognized as a potential biomarker of breast tumor
      development. Abrogating MCT-1 function may be a promising stratagem for
      management of breast cancer involving Src hyperactivation and/or PTEN
      dysfunction.

PMID- 24858044
TI  - miR-200a-mediated suppression of non-muscle heavy chain IIb inhibits meningioma
      cell migration and tumor growth in vivo.
AB  - miR-200a has been implicated in the pathogenesis of meningiomas, one of the most
      common central nervous system tumors in humans. To identify how miR-200a
      contributes to meningioma pathogenesis at the molecular level, we used a
      comparative protein profiling approach using Gel-nanoLC-MS/MS and identified
      approximately 130 dysregulated proteins in miR-200a-overexpressing meningioma
      cells. Following the bioinformatic analysis to identify potential genes targeted
      by miR-200a, we focused on the non-muscle heavy chain IIb (NMHCIIb), and showed
      that miR-200a directly targeted NMHCIIb. Considering the key roles of NMHCIIb in
      cell division and cell migration, we aimed to identify whether miR-200a regulated
      these processes through NMHCIIb. We found that NMHCIIb overexpression partially
      rescued miR-200a-mediated inhibition of cell migration, as well as cell growth in
      vitro and in vivo. Moreover, siRNA-mediated silencing of NMHCIIb expression
      resulted in a similar migration phenotype in these cells and inhibited meningioma
      tumor growth in mice. Taken together, these results suggest that NMHCIIb might
      serve as a novel therapeutic target in meningiomas.

PMID- 24858045
TI  - Less understood issues: p21(Cip1) in mitosis and its therapeutic potential.
AB  - p21(Cip1) is a multifunctional protein and a key player in regulating different
      cellular processes. The transcription of p21 is regulated by p53-dependent and 
      independent pathways. The expression of p21 is increased in response to various
      cellular stresses to arrest the cell cycle and ensure genomic stability. p21 has
      been shown to be a tumor suppressor and an oncogene as well. The function of p21
      in mitosis has been proposed but not systematically studied. We have recently
      shown that p21 binds to and inhibits the activity of Cdk1/cyclin B1, and is
      important for a fine-tuned mitotic progression. Loss of p21 prolongs the duration
      of mitosis and results in severe mitotic defects like chromosome segregation and
      cytokinesis failures promoting consequently genomic instability. Moreover, p21 is
      dramatically stabilized in mitotic tumor cells upon treatment with mitotic agents
      like paclitaxel or mitotic kinase inhibitors. Increased p21 is mainly localized
      in the cytoplasm and associates with cell survival indicating a crucial role of
      p21 in susceptibility to mitotic agents in tumor cells. In this review we will
      briefly summarize the structure and general physiological functions as well as
      regulation of p21, discuss in detail its role in mitosis and its potential to
      serve as a therapeutic target.

PMID- 24858046
TI  - Cooperation of Blm and Mus81 in development, fertility, genomic integrity and
      cancer suppression.
AB  - BLM is a DNA helicase important for the restart of stalled replication forks and
      for homologous recombination (HR) repair. Mutations of BLM lead to Bloom
      Syndrome, a rare autosomal recessive disorder characterized by elevated levels of
      sister chromatid exchanges (SCEs), dwarfism, immunodeficiency, infertility and
      increased cancer predisposition. BLM physically interacts with MUS81, an
      endonuclease involved in the restart of stalled replication forks and HR repair.
      Herein we report that loss of Mus81 in Blm hypomorph mutant mice leads to
      infertility, and growth and developmental defects that are not observed in single
      mutants. Double mutant cells and mice were hypersensitive to Mitomycin C and
      gamma-irradiation (IR) compared with controls and their repair of DNA double
      strand breaks (DSBs) mediated by HR pathway was significantly defective, whereas
      their non-homologous-end-joining repair was elevated compared with controls. We
      also demonstrate the importance of the loss of the nuclease activity of Mus81 in
      the defects observed in Mus81(-/-) and double mutant cells. Exacerbated IR
      induced chromosomal aberration was observed in double mutant mice and despite
      their reduced SCE levels, these mutants showed increased tumorigenesis risks. Our
      data highlight the importance of Mus81 and Blm in DNA DSB repair pathways,
      fertility, development and cancer.

PMID- 24858047
TI  - Functional antagonism between pro-apoptotic BIM and anti-apoptotic BCL-XL in MYC
      induced lymphomagenesis.
AB  - Genomic analyses revealed that many cancers have acquired abnormalities in their
      expression of pro- or anti-apoptotic members of the BCL-2 protein family. It is,
      however, unknown whether changes in pro- or anti-apoptotic BCL-2 family members
      have similar impact on tumorigenesis or whether changes in one subgroup have
      disproportionate impact. We compared the consequences of concomitant loss of anti
      apoptotic Bclx and pro-apoptotic Bim on MYC-induced lymphomagenesis. Whereas only
      loss of both Bclx alleles markedly forestalled tumorigenesis, loss of a single
      Bim allele overcame this blockade. Conversely, loss of even a single Bim allele
      sufficed to substantially accelerate lymphomagenesis, and only loss of both but
      not loss of a single allele of Bclx could attenuate this acceleration. The
      evidence that modest (two-fold) monoallelic changes in the expression of at least
      some BH3-only proteins can profoundly impact tumorigenesis suggests that such
      aberrations, imposed by epigenetic or genetic changes, may expedite tumorigenesis
      more effectively than elevated expression of pro-survival BCL-2 family members.
      These findings further our understanding of the mechanisms of lymphomagenesis and
      possibly also cancer therapy.

PMID- 24858049
TI  - Evaluating the potential for environmental pollution from chromated copper
      arsenate (CCA)-treated wood waste: a new mass balance approach.
AB  - The potential for pollution from arsenic, chromium and copper in chromated copper
      arsenate (CCA) treated wood waste was assessed using two lysimeter studies. The
      first utilised lysimeters containing soil and CCA wood waste mulch exposed to
      natural conditions over a five month period. The second study used the same
      lysimeter setup in a regulated greenhouse setting with a manual watering regime.
      Woodchip, soil and leachate samples were evaluated for arsenic, chromium and
      copper concentrations. Resultant concentration data were used to produce mass
      balances, an approach thus far unused in such studies. This novel analysis
      revealed new patterns of mobility and distribution of the elements in the system.
      The results suggest that CCA wood waste tends to leach on initial exposure to a
      leachant and during weathering of the wood. When in contact with soil,
      metal(loid) transport is reduced due to complexation reactions. With higher water
      application or where the adsorption capacity of the soil is exceeded, the
      metal(loid)s are transported through the soil column as leachate. Overall, there
      was an unexplained loss of metal(loid)s from the system that might be attributed
      to volatilisation of arsenic and plant uptake. This suggests a hitherto
      unidentified risk to both the environment and human health. 

PMID- 24858050
TI  - Daily intake of polybrominated diphenyl ethers via dust and diet from an e-waste
      recycling area in China.
AB  - This study was designed to estimate the human risk to polybrominated diphenyl
      ethers (PBDEs) exposure via two main exposure routes (dust and diet) in an e
      waste recycling area in southern China. A total of 134 dust samples and 129 food
      samples were analyzed by gas chromatography/mass spectrometry (GC/MS). The mean
      concentration of SigmaPBDE in in-house dust (38,685ng/g dw) was higher than that
      in out-house dust (24,595ng/g). For food samples, the highest concentration of
      SigmaPBDE was found in fish and shellfish (2755ng/kg ww), followed in descending
      order by eggs (2423ng/kg), cereals (2239ng/kg) and meat (1799ng/kg). The
      estimated total daily dietary intake of PBDEs was 1671ng/day for adults and
      952ng/day for children. The present study indicated that dust intake was the
      dominant PBDE exposure route for children, and the dietary intake was the
      dominant PBDE exposure route for adults. Our findings revealed high PBDE
      concentrations in dust and food samples collected at the center of e-waste
      recycling area, raising significant health concerns for residents in this
      particular region, especially for children. 

PMID- 24858051
TI  - Carbon material formation on SBA-15 and Ni-SBA-15 and residue constituents during
      acetylene decomposition.
AB  - Carbon materials including carbon spheres and nanotubes were formed from
      acetylene decomposition on hydrogen-reduced SBA-15 and Ni-SBA-15 at 650-850
      degrees C. The physicochemical characteristics of SBA-15, Ni-SBA-15 and carbon
      materials were analyzed by field emission scanning electronic microscopy (FE
      SEM), Raman spectrometry, and energy dispersive spectrometry (EDS). In addition,
      the contents of polyaromatic hydrocarbons (PAHs) in the tar and residue and
      volatile organic compounds (VOCs) in the exhaust were determined during acetylene
      decomposition on SBA-15 and Ni-SBA-15. Spherical carbon materials were observed
      on SBA-15 during acetylene decomposition at 750 and 850 degrees C. Carbon
      filaments and ball spheres were formed on Ni-SBA-15 at 650-850 degrees C. Raman
      spectroscopy revealed peaks at 1290 (D-band, disorder mode, amorphous carbon) and
      1590 (G-band, graphite sp(2) structure)cm(-1). Naphthalene (2 rings), pyrene (4
      rings), phenanthrene (3 rings), and fluoranthene (4 rings) were major PAHs in tar
      and residues. Exhaust constituents of hydrocarbon (as propane), H2, and C2H2 were
      3.9-2.6/2.7-1.5, 1.4-2.8/2.6-4.3, 4.2-2.4/3.2-1.7% when acetylene was decomposed
      on SBA-15/Ni-SBA-15, respectively, corresponding to temperatures ranging from 650
      to 850 degrees C. The concentrations of 52 VOCs ranged from 9359 to 5658 and 2488
      to 1104ppm for SBA-15 and Ni-SBA-15 respectively, at acetylene decomposition
      temperatures from 650 to 850 degrees C, and the aromatics contributed more than
      87% fraction of VOC concentrations. 

PMID- 24858052
TI  - Quantitative study of age-related endothelial phenotype change in the human
      vortex vein system.
AB  - PURPOSE: We have previously reported significant phenotype heterogeneity in the
      vortex vein system. This study is to quantify the age-related change of such
      endothelial phenotype heterogeneity. METHOD: The inferior temporal vortex vein
      system of 10 eyes from 7 young donors (30+/-4.1 years) and 9 eyes from 6 aged
      (72+/-4.7 years) donors were dissected after perfusion fixation and labeled for f
      actin and nucleic acid. Confocal images of endothelial cells were obtained from
      nine anatomic regions and measurements made of the cell and nucleus sizes. The
      results were compared between the two age groups. RESULTS: Similar regional
      endothelial heterogeneity was observed in both age groups through the different
      regions of the vortex vein system. Age-related increase in endothelial cell area
      was observed in all the study regions. Age-associated regional differences were
      also observed in the endothelial length, width, and nucleus parameters.
      Endothelial nuclei were also found to be located further downstream within the
      cell in aged donor eyes. CONCLUSION: Age related enlarged endothelial cells have
      been identified in this venous system, a likely indicator of senescence. The
      relationship between the endothelial senescence, regional endothelial phenotype
      change and endothelial dysfunction in possible pathological changes needs to be
      further defined.

PMID- 24858053
TI  - New ESPGHAN Editor: some thoughts on JPGN.

PMID- 24858054
TI  - The prevalence and prognostic effects of subclinical thyroid dysfunction in
      dilated cardiomyopathy patients: a single-center cohort study.
AB  - BACKGROUND: Subclinical thyroid dysfunction may be a risk factor for mortality in
      patients with heart failure and may be associated with dilated cardiomyopathy
      (DCM). This was a cohort study to examine the possible association between
      subclinical thyroid dysfunction and all-cause mortality in DCM patients, because
      the current evidence on this association remains elusive. METHODS AND RESULTS: A
      total of 963 DCM patients were evaluated for thyroid function. Of these patients,
      7.1% (n = 68) had subclinical hyperthyroidism (defined as serum thyroid
      stimulating hormone [TSH] <0.35 MUIU/mL), 84.7% (n = 816) had euthyroidism (TSH
      0.35-5.5 MUIU/mL), and 8.2% (n = 79) had subclinical hypothyroidism (TSH >5.5
      MUIU/mL). There was a significant difference in all-cause mortality rates between
      patients with euthyroidism and patients with subclinical hyper- and
      hypothyroidism (21%, 38.2%, and 26.6%, respectively; log-rank chi(2) = 13.104; P
      = .001) with mean follow-up of 3.5 years. After adjustment for other confounding
      factors at baseline, QRS duration, N-terminal pro-B-type natriuretic peptide, New
      York Heart Association functional class, left atrial diameter, and subclinical
      hyperthyroidism (hazard ratio 1.793, 95% CI 1.010-3.183; P = .046) emerged as
      significant predictors of all-cause mortality. CONCLUSION: DCM patients with
      subclinical hyper- and hypothyroidism had higher all-cause mortality rates.
      However, only subclinical hyperthyroidism, not subclinical hypothyroidism, was an
      independent predictor for increased risk of all-cause mortality.

PMID- 24858055
TI  - An international survey to assess referral thresholds for destination therapy in
      non-inotrope-dependent patients: results of the CONSENSUS-DT study.
AB  - BACKGROUND: Criteria for the identification of patients who may progress to
      advanced heart failure (HF) have been previously suggested. However,
      identification of appropriate non-inotrope-dependent (NID) patients for
      destination therapy (DT) remains a challenge, and referral rates are low. We
      surveyed expert provider opinion about patient selection for early DT. METHODS:
      An internet-based survey was sent to international HF providers to investigate
      opinions about clinical indicators for referral of NID patients for DT. Subjects
      were identified from membership lists of HF professional organizations.
      Respondents provided their level of agreement with the use of a 5-point Likert
      Scale (1 = strongly disagree to 5 = strongly agree) to 10 clinical criteria
      describing at-risk NID patients. RESULTS: A total of 231 respondents who had been
      in a position to recommend left ventricular assist device (LVAD) therapy for 7.6
      +/- 5.8 years identified themselves as HF providers: 41% HF cardiologists, 27% HF
      nurse practitioners, 21% cardiothoracic surgeons, 9% LVAD coordinators, and 2%
      general cardiologists. More than two-thirds of the respondents agreed or strongly
      agreed with 7 of the 10 items. Similar consensus was not seen for 6-minute walk
      (6MW) or B-type natriuretic peptide (BNP). When asked which criteria would have
      to be present for LVAD referral, only hemodynamic deterioration reached >=50%
      affirmation among respondents. No criteria reached >50% response as being
      sufficient alone for DT. CONCLUSION: We describe referral thresholds for early
      LVAD therapy among international HF providers. With the exception of BNP and 6MW,
      we found overall agreement on the proposed clinical parameters. Despite apparent
      consensus, in practice implantation rates for LVAD in NID patients remain low.
      The results of ongoing clinical trials in this population may lower thresholds
      for early referral for DT.

PMID- 24858056
TI  - Comparison of office, home, and ambulatory blood pressure in heart transplant
      recipients.
AB  - BACKGROUND: The purpose of this study was to prospectively evaluate the
      relationship between office, home, and ambulatory blood pressure (BP) in heart
      transplant recipients. METHODS AND RESULTS: The study enrolled 30 adults >= 6
      months after heart transplantation. Morning seated office BP was measured with
      the use of an automatic device at 3 outpatient visits. Seated home BP was
      measured in the morning and evening for 5 consecutive days. Ambulatory BP was
      measured over 24 hours with the use of a Spacelabs monitor. The strongest
      correlation was observed between home and 24-hour ambulatory BP (r = 0.79
      systolic; r = 0.72 diastolic). Office and home systolic BPs were significantly
      lower than daytime ambulatory BP (office, -3.7 mm Hg, P = .009; home, -2.6 mm Hg,
      P = .05). Ambulatory monitoring identified more participants with BP above
      hypertensive limits than did office or home measurements (63%, 50%, and 13%,
      respectively; P = .003). Ambulatory monitoring also revealed high BP loads,
      abnormal nocturnal BP patterns (eg, 30% nondippers), and a high percentage of
      masked hypertension (37% home, 50% ambulatory). CONCLUSIONS: Office and home BP
      monitoring are acceptable but may underestimate BP burden in heart transplant
      recipients. Additional studies are needed to determine which BP method is
      superior for the management of hypertension and associated outcomes after heart
      transplantation.

PMID- 24858057
TI  - Regulation of rotenone-induced microglial activation by 5-lipoxygenase and
      cysteinyl leukotriene receptor 1.
AB  - The 5-lipoxygenase (5-LOX) products cysteinyl leukotrienes (CysLTs) are potent
      pro-inflammatory mediators. CysLTs mediate their biological actions through
      activating CysLT receptors (CysLT(1)R and CysLT(2)R). We have recently reported
      that 5-LOX and CysLT(1)R mediated PC12 cell injury induced by high concentrations
      of rotenone (0.3-10 MUM), which was reduced by the selective 5-LOX inhibitor
      zileuton and CysLT(1)R antagonist montelukast. The purpose of this study was to
      examine the regulatory roles of the 5-LOX/CysLT(1)R pathway in microglial
      activation induced by low concentration rotenone. After mouse microglial BV2
      cells were stimulated with rotenone (0.3-3 nM), phagocytosis and release of pro
      inflammatory cytokine were assayed as indicators of microglial activation. We
      found that rotenone (1 and 3 nM) increased BV2 microglial phagocytosis and the
      release of the pro-inflammatory cytokines interleukin-1beta (IL-1beta) and tumor
      necrosis factor-alpha (TNF-alpha). Zileuton and montelukast prevented rotenone (3
      nM)-induced phagocytosis and cytokine release. Furthermore, rotenone
      significantly up-regulated 5-LOX expression, induced 5-LOX translocation to the
      nuclear envelope, and increased the production of CysLTs. These responses were
      inhibited by zileuton. Rotenone also increased CysLT(1)R expression and induced
      nuclear translocation of CysLT(1)R. In primary rat microglia, rotenone (10 nM)
      increased release of IL-1beta and TNF-alpha, whereas zileuton (0.1 MUMU) and
      montelukast (0.01 MUMU) significantly inhibited this response. These results
      indicated that 5-LOX and CysLT(1)R might be key regulators of microglial
      activation induced by low concentration of rotenone. Interference of 5
      LOX/CysLT(1)R pathway may be an effective therapeutic strategy for microglial
      inflammation.

PMID- 24858058
TI  - Prediction of binding affinities of PCDDs, PCDFs and PCBs using docking-based
      Comparative Molecular Similarity Indices Analysis.
AB  - Polychlorinated Dibenzodioxins (PCDDs), Dibenzofurans (PCDFs) and Biphenyls
      (PCBs) are industrial compounds or byproducts that can cause toxic effects after
      binding to aryl hydrocarbon receptor (AhR). But the mechanism about PCDDs, PCDFs
      and PCBs binding to AhR is unclear. To study the interaction and significant
      amino acid residues in binding of PCDDs, PCDFs and PCBs to AhR, a docking-based
      Comparative Molecular Similarity Indices Analysis (CoMSIA) was performed on a set
      of structurally diverse PCDDs, PCDFs and PCBs with known binding affinities. The
      docking-based CoMSIA model (non-cross-validated regression coefficient of 0.942
      and cross-validated regression coefficient of 0.768) was developed and compared
      with previous report, the presented docking-based CoMSIA model showed good
      robustness and predictive performance. The obtained docking conformations and
      predictive CoMSIA model could provide clues to understand key residues and
      interactions between receptor and compounds of interest. 

PMID- 24858059
TI  - The medicinal fungus Antrodia cinnamomea suppresses inflammation by inhibiting
      the NLRP3 inflammasome.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Antrodia cinnamomea--a medicinal fungus that is
      indigenous to Taiwan--has been used as a health tonic by aboriginal tribes and
      the Asian population. Recent studies indicate that Antrodia cinnamomea extracts
      exhibit hepato-protective, anti-hypertensive, anti-oxidative, anti-inflammatory,
      immuno-modulatory, and anti-cancer effects on cultured cells and laboratory
      animals. This study aims to explore the anti-inflammatory activity of an Antrodia
      cinnamomea ethanol extract (ACEE) and elucidate its underlying mechanisms of
      action using lipopolysaccharide (LPS)-primed, ATP-stimulated human THP-1
      macrophages. MATERIALS AND METHODS: The effects of ACEE on cell viability were
      studied using the MTT assay. The expressions of genes, proteins, and pro
      inflammatory cytokines were measured by quantitative real-time RT-PCR, Western
      blotting and ELISA, respectively. The ACEE was further investigated for its
      effects on reactive oxygen species (ROS) production using ROS detection kit.
      RESULTS: Our results showed that ACEE significantly inhibits ATP-induced
      secretion of interleukin-1beta (IL-1beta), interleukin-18 (IL-18) and tumor
      necrosis factor-alpha (TNF-alpha) by LPS-primed macrophages. ACEE also suppresses
      the transcription and activation of caspase-1, which is responsible for the
      cleavage and activation of IL-1beta and IL-18. Of note, ACEE not only reduces
      expression of the inflammasome component NLRP3 and the purinergic receptor P2X7R
      but also inhibits ATP-induced ROS production and caspase-1 activation.
      Furthermore, the anti-inflammatory properties of ACEE correlate with reduced
      activation of the MAPK and NF-kappaB pathways. CONCLUSION: The results of the
      present study indicate that Antrodia cinnamomea suppresses the secretion of IL
      1beta and IL-18 associated with inhibition of the NLRP3 inflammasome in
      macrophages. These findings suggest that ACEE may have therapeutic potential for
      the treatment of inflammatory diseases.

PMID- 24858060
TI  - Dietary manipulation of platelet function.
AB  - Activated platelets contribute to plaque formation within blood vessels in the
      early and late stages of atherogenesis, and therefore they have been proposed as
      risk factor for cardiovascular disease. Anti-platelet drugs, such as aspirin, are
      now the most prescribed pharmacological treatment in Europe. Certain dietary
      bioactives also beneficially affect platelet function, and with less side
      effects, albeit that effects are generally more subtle. Therefore, consumption of
      dietary bioactives could play a role in the prevention of atherothrombotic
      vascular disease. Here we review the efficacy of dietary treatment strategies,
      especially those involving certain dietary fatty acids and polyphenols, to
      modulate platelet function in healthy subjects or in patients with cardiovascular
      disease. Variation in study populations, small study sizes and lack of
      comparability between methods to assess platelet function currently limit robust
      evidence on the efficacy of dietary bioactives in healthy subjects or specific
      patient groups. Also, limited knowledge of the metabolism of dietary bioactives,
      and therefore of the bioavailability of bioactive ingredients, restricts our
      ability to identify the most effective dietary regimes to improve platelet
      function. Implementation of uniform point-of-care tests to assess platelet
      function, and enhanced knowledge of the efficacy by which specific dietary
      compounds and their metabolites affect platelet function, may enable the
      identification of functional anti-platelet ingredients that are eligible for a
      health claim, or combined treatment strategies, including both pharmacological
      anti-platelet treatment as well as dietary intervention, to tackle
      atherothrombotic vascular disease. 

PMID- 24858061
TI  - Lack of blood pressure-lowering effect of renal denervation in a drug-naive
      patient with pronounced arterial stiffening.

PMID- 24858062
TI  - SAMe-TT2R2 score, time in therapeutic range, and outcomes in anticoagulated
      patients with atrial fibrillation.
AB  - BACKGROUND: Oral anticoagulation is highly effective in preventing stroke and
      mortality in nonvalvular atrial fibrillation patients. However, the efficacy and
      safety of vitamin K antagonists (the main oral anticoagulation drug used)
      strongly depends upon the quantity of anticoagulation control, as reflected by
      the average percentage of the time in therapeutic range of international
      normalized ratio 2.0-3.0. An easy, simple prediction of which atrial fibrillation
      patients are likely to do well on vitamin K antagonists (with good average time
      in therapeutic range) could guide decision-making between using vitamin K
      antagonists (eg, warfarin) and non-vitamin K antagonist oral anticoagulants.
      METHODS AND RESULTS: In a consecutive cohort of nonvalvular atrial fibrillation
      patients attending our anticoagulation clinic, we tested the hypothesis that the
      new Sex, Race, Medical history, Tobacco use, Race (SAMe-TT2R2) score was a
      predictor for good average time in therapeutic range, and second, this would
      translate into adverse events in a "real world" cohort of patients with
      nonvalvular atrial fibrillation. The incidence of bleeding, adverse
      cardiovascular events (including stroke/thromboembolism), and mortality during
      the follow-up was higher with increasing SAMe-TT2R2 score. The SAMe-TT2R2 score
      was predictive for the composite of all adverse events (hazard ratio 1.32 [95%
      Confidence Interval 1.17-1.50]; P <.001), adverse cardiovascular events (1.52
      [1.28-1.83]; P <.001), and all-cause mortality (1.41 [1.16-1.67]; P = .001). A
      trend was also observed for major bleeding events (1.23 [0.99-1.53]; P = .059).
      CONCLUSION: In a "real world" cohort of consecutive patients with nonvalvular
      atrial fibrillation, a high SAMe-TT2R2 score (reflecting poor anticoagulation
      control with poor time in therapeutic range) was associated with more bleeding,
      adverse cardiovascular events, and mortality during follow-up.

PMID- 24858063
TI  - Philanthropy, medical research, and the role of development.

PMID- 24858064
TI  - New thinking about honor and deceased organ donation.

PMID- 24858065
TI  - Do roads reduce painted turtle (Chrysemys picta) populations?
AB  - Road mortality is thought to be a leading cause of turtle population decline.
      However, empirical evidence of the direct negative effects of road mortality on
      turtle population abundance is lacking. The purpose of this study was to provide
      a strong test of the prediction that roads reduce turtle population abundance.
      While controlling for potentially confounding variables, we compared relative
      abundance of painted turtles (Chrysemys picta) in 20 ponds in Eastern Ontario, 10
      as close as possible to high traffic roads (Road sites) and 10 as far as possible
      from any major roads (No Road sites). There was no significant effect of roads on
      painted turtle relative abundance. Furthermore, our data do not support other
      predictions of the road mortality hypothesis; we observed neither a higher
      relative frequency of males to females at Road sites than at No Road sites, nor a
      lower average body size of turtles at Road than at No Road sites. We speculate
      that, although roads can cause substantial adult mortality in turtles, other
      factors, such as release from predation on adults and/or nests close to roads
      counter the negative effect of road mortality in some populations. We suggest
      that road mitigation for painted turtles can be limited to locations where
      turtles are forced to migrate across high traffic roads due, for example, to
      destruction of local nesting habitat or seasonal drying of ponds. This conclusion
      should not be extrapolated to other species of turtles, where road mortality
      could have a larger population-level effect than on painted turtles. 

PMID- 24858066
TI  - Children with mathematical learning disability fail in recruiting verbal and
      numerical brain regions when solving simple multiplication problems.
AB  - Greater skill in solving single-digit multiplication problems requires a
      progressive shift from a reliance on numerical to verbal mechanisms over
      development. Children with mathematical learning disability (MD), however, are
      thought to suffer from a specific impairment in numerical mechanisms. Here we
      tested the hypothesis that this impairment might prevent MD children from
      transitioning toward verbal mechanisms when solving single-digit multiplication
      problems. Brain activations during multiplication problems were compared in MD
      and typically developing (TD) children (3rd to 7th graders) in numerical and
      verbal regions which were individuated by independent localizer tasks. We used
      small (e.g., 2 * 3) and large (e.g., 7 * 9) problems as these problems likely
      differ in their reliance on verbal versus numerical mechanisms. Results indicate
      that MD children have reduced activations in both the verbal (i.e., left inferior
      frontal gyrus and left middle temporal to superior temporal gyri) and the
      numerical (i.e., right superior parietal lobule including intra-parietal sulcus)
      regions suggesting that both mechanisms are impaired. Moreover, the only reliable
      activation observed for MD children was in the numerical region when solving
      small problems. This suggests that MD children could effectively engage numerical
      mechanisms only for the easier problems. Conversely, TD children showed a
      modulation of activation with problem size in the verbal regions. This suggests
      that TD children were effectively engaging verbal mechanisms for the easier
      problems. Moreover, TD children with better language skills were more effective
      at engaging verbal mechanisms. In conclusion, results suggest that the numerical-
      and language-related processes involved in solving multiplication problems are
      impaired in MD children. 

PMID- 24858067
TI  - A panel of serum biomarkers differentiates IgA nephropathy from other renal
      diseases.
AB  - BACKGROUND AND OBJECTIVES: There is increasing evidence that galactose-deficient
      IgA1 (Gd-IgA1) and Gd-IgA1-containing immune complexes are important for the
      pathogenesis of IgA nephropathy (IgAN). In the present study, we assessed a novel
      noninvasive multi-biomarker approach in the diagnostic test for IgAN. MATERIALS
      AND METHODS: We compared serum levels of IgA, IgG, Gd-IgA1, Gd-IgA1-specific IgG
      and Gd-IgA1-specific IgA in 135 IgAN patients, 79 patients with non-IgAN chronic
      kidney disease (CKD) controls and 106 healthy controls. Serum was collected at
      the time of kidney biopsy from all IgAN and CKD patients. RESULTS: Each serum
      marker was significantly elevated in IgAN patients compared to CKD (P<0.001) and
      healthy controls (P<0.001). While 41% of IgAN patients had elevated serum Gd-IgA1
      levels, 91% of these patients exhibited Gd-IgA1-specific IgG levels above the
      90th percentile for healthy controls (sensitivity 89%, specificity 92%). Although
      up to 25% of CKD controls, particularly those with immune-mediated glomerular
      diseases including lupus nephritis, also had elevated serum levels of Gd-IgA1
      specific IgG, most IgAN patients had elevated levels of Gd-IgA1-specific antibody
      of both isotypes. Serum levels of Gd-IgA1-specific IgG were associated with renal
      histological grading. Furthermore, there was a trend toward higher serum levels
      of Gd-IgA1-specific IgG in IgAN patients with at least moderate proteinuria
      (>=1.0 g/g), compared to patients with less proteinuria. CONCLUSIONS: Serum
      levels of Gd-IgA1-specific antibodies are elevated in most IgAN patients, and
      their assessment, together with serum levels of Gd-IgA1, improves the specificity
      of the assays. Our observations suggest that a panel of serum biomarkers may be
      helpful in differentiating IgAN from other glomerular diseases.

PMID- 24858070
TI  - Outcomes in World Health Organization group II pulmonary hypertension: mortality
      and readmission trends with systolic and preserved ejection fraction-induced
      pulmonary hypertension.
AB  - BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) has been
      increasingly recognized as a leading cause of pulmonary hypertension (HFpEF-PH).
      It remains unknown how HFpEF-PH fares in relation to systolic HF (reduced
      ejection fraction)-induced PH (HFrEF-PH). Therefore, we sought to determine the
      long-term morbidity and mortality of HFpEF-PH and HFrEF-PH. METHODS AND RESULTS:
      We studied all patients over a 6-year period with symptomatic HF and severe PH
      (PASP >=65 mm Hg) in The Bronx, New York. We classified patients as having either
      preserved (>=50%) or reduced (<=35%) left ventricular ejection fraction. Trends
      in mortality and HF readmission rates were defined in 650 patients (HFrEF-PH: n =
      277; HFpEF-PH: n = 373). HFpEF-PH patients were older and more often female and
      white. HFrEF-PH patients were more often black, had ischemic cardiomyopathy, and
      were on typical HF drug regimens. Patients with HFpEF-PH had a significantly
      increased all-cause 5-year mortality (52% vs 42%; P = .024). HFpEF-PH was a
      significant predictor of mortality (adjusted hazard ratio 1.70; P = .012).
      Patients with HFrEF-PH had more HF readmissions (>=1) than patients with HFpEF-PH
      (28.6% vs 15%; P = .003), especially within the 1st year (9.1% vs 1.7%; P =
      .005). CONCLUSIONS: Patients with HFrEF-PH and HFpEF-PH have a significantly
      elevated long-term mortality, with HFpEF-PH having a higher 5-year mortality
      rate. These findings testify to the overall poor prognosis of World Health
      Organization Group II PH, especially HFpEF-PH.

PMID- 24858071
TI  - miRNA microarray reveals specific expression in the peripheral blood of
      glioblastoma patients.
AB  - MicroRNAs (miRNAs) are frequently dysregulated in glioblastoma (GBM) patients. It
      has been discovered that highly stable extracellular miRNAs circulate in the
      blood of both healthy individuals and patients. miRNAs in serum of patients with
      GBM and normal controls were analyzed by microarray analysis. The relevant
      bioinformatic analysis of the predicted target genes (gene ontology, pathway,
      gene network analysis) were performed. The miRNA microarray reveals
      differentially expressed miRNAs in serum between the GBM and normal controls. Of
      the 752 miRNAs, 115 miRNAs were upregulated in the GBM group, and 24 miRNAs were
      downregulated (fold change >=2.0, P<0.01). By further analysis, we found that miR
      576-5p, miR-340 and miR-626 were significantly overexpressed, but miR-320, let-7g
      5p and miR-7-5P showed significantly low expression in GBM patients. By further
      bioinformatic analysis, we found that they possibly play important roles in the
      regulation of glioma signaling pathways. In summary, the six miRNAs are
      significant distinct in the peripheral blood of patients with GBM pathologies.
      These data suggest that the miRNA profile of the peripheral blood may serve as a
      new biomarker for glioma diagnosis with high specificity and sensitivity.

PMID- 24858072
TI  - Engineering vascularized bone grafts by integrating a biomimetic periosteum and
      beta-TCP scaffold.
AB  - Treatment of large bone defects using synthetic scaffolds remain a challenge
      mainly due to insufficient vascularization. This study is to engineer a
      vascularized bone graft by integrating a vascularized biomimetic cell-sheet
      engineered periosteum (CSEP) and a biodegradable macroporous beta-tricalcium
      phosphate (beta-TCP) scaffold. We first cultured human mesenchymal stem cells
      (hMSCs) to form cell sheet and human umbilical vascular endothelial cells
      (HUVECs) were then seeded on the undifferentiated hMSCs sheet to form
      vascularized cell sheet for mimicking the fibrous layer of native periosteum. A
      mineralized hMSCs sheet was cultured to mimic the cambium layer of native
      periosteum. This mineralized hMSCs sheet was first wrapped onto a cylindrical
      beta-TCP scaffold followed by wrapping the vascularized HUVEC/hMSC sheet, thus
      generating a biomimetic CSEP on the beta-TCP scaffold. A nonperiosteum structural
      cell sheets-covered beta-TCP and plain beta-TCP were used as controls. In vitro
      studies indicate that the undifferentiated hMSCs sheet facilitated HUVECs to form
      rich capillary-like networks. In vivo studies indicate that the biomimetic CSEP
      enhanced angiogenesis and functional anastomosis between the in vitro preformed
      human capillary networks and the mouse host vasculature. MicroCT analysis and
      osteocalcin staining show that the biomimetic CSEP/beta-TCP graft formed more
      bone matrix compared to the other groups. These results suggest that the CSEP
      that mimics the cellular components and spatial configuration of periosteum plays
      a critical role in vascularization and osteogenesis. Our studies suggest that a
      biomimetic periosteum-covered beta-TCP graft is a promising approach for bone
      regeneration. 

PMID- 24858074
TI  - Cloning, expression and characterization of a gene encoding mitogen activated
      protein kinase 2 (MPK2) from Tetrahymena thermophila.
AB  - Environmental effects and mitogens determine cell phenotype in eukaryotes mainly
      through MAPK pathways. However, MAPK signaling pathways in T. thermophila have
      not been studied comprehensively. This study aims to express recombinant MPK2, a
      MAPK from T. thermophila, in E. coli to characterize its kinase activity. MPK2
      was cloned by RT-PCR using degenerate oligonucleotide primers and RACE method.
      The full-length cDNA of the MPK2 gene is 1705bp that includes 1281bp ORF coding
      for a putative protein of 426 amino acids having a mass of 50.2kDa. The putative
      MPK2 protein contains all eleven conserved subdomains that are characteristics of
      serine/threonine protein kinases, and a TDY motif, which is a putative dual
      phosphorylation site common in Protista. MPK2 displays highest 48% overall
      identity to human ERK5 (MAPK7). The expression vector pGEX4T-1-MPK2 was
      constructed by inserting the coding region of MPK2 cDNA into pGEX4T-1 after
      introducing the nine point mutations, and then transformed into E. coli
      BL21(DE3). Autophosphorylation of 76kDa GST-MPK2 at tyrosine residues was
      confirmed not only by Western blot using anti-phosphotyrosine monoclonal antibody
      but also by in vitro kinase assay. GST-MPK2 was also able to phosphorylate the
      artificial substrate myelin basic protein. This study concludes that the free
      living unicellular protist T. thermophila MPK2 has commonly conserved MAPK enzyme
      features, possibly involved in the regulation of cell survival responding to
      abiotic or biotic stressors, and the production and movement of haploid gametic
      nuclei between pairs during conjugation.

PMID- 24858075
TI  - K-mer natural vector and its application to the phylogenetic analysis of genetic
      sequences.
AB  - Based on the well-known k-mer model, we propose a k-mer natural vector model for
      representing a genetic sequence based on the numbers and distributions of k-mers
      in the sequence. We show that there exists a one-to-one correspondence between a
      genetic sequence and its associated k-mer natural vector. The k-mer natural
      vector method can be easily and quickly used to perform phylogenetic analysis of
      genetic sequences without requiring evolutionary models or human intervention.
      Whole or partial genomes can be handled more effective with our proposed method.
      It is applied to the phylogenetic analysis of genetic sequences, and the
      obtaining results fully demonstrate that the k-mer natural vector method is a
      very powerful tool for analysing and annotating genetic sequences and determining
      evolutionary relationships both in terms of accuracy and efficiency.

PMID- 24858076
TI  - Global DNA hypomethylation: a potential mechanism in King pigeon nerve tissue
      damage induced by avermectin.
AB  - As an effective insecticidal and nematicidal agent, avermectin (AVM) has been
      widely used in agricultural production and stock farming areas. Subsequently, the
      residues of AVM or its active metabolites in animal manure pose a toxic threat to
      non-target organisms in the environment. As the most characteristic epigenetic
      phenomena, DNA methylation status is a useful biological signal for the toxicity
      assessment of environmental chemical toxicants. In this study, analyses of the
      overall level of genomic DNA methylation were performed, and the expression
      levels of DNA methyltransferases (DNMTs), as well as demethylase methyl-CpG
      binding domain protein 2 (MBD2), in pigeon brain tissues after subchronic
      exposure (with a AVM concentration of 20 mg/kg, 40 mg/kg and 60 mg/kg,
      respectively) to AVM for 30, 60 and 90 days were investigated. Global DNA
      hypomethylation and down-regulation of DNMT mRNA expression occurred in a dose
      time-dependent manner in pigeon brains. The expression level of MBD2, which
      functions as a demethylase, was significantly enhanced in a dose-dependent but
      not time-dependent manner. In addition, the elevated expression level of MBD2 had
      a more robust effect on genomic DNA hypomethylation compared to changes in DNMT
      expression. Taken together, these results suggested that subchronic dose
      exposures of AVM could affect the global DNA methylation status, and this
      mechanism is closely related to changes in the expression levels of DNMTs and
      MBD2.

PMID- 24858077
TI  - Cucurbitacin-I, a natural cell-permeable triterpenoid isolated from
      Cucurbitaceae, exerts potent anticancer effect in colon cancer.
AB  - Cucurbitacin-I is a triterpenoids found in medicinal plants and have diverse
      pharmacological and biological activities. In this study, the antitumor effects
      of cucurbitacin-I on colon cancer and possible roles in apoptosis and cell cycle
      arrest were investigated. Treatment of SW480 cells, a human colon cancer cells,
      with cucurbitacin-I decreased cell viability and cell proliferation in a
      concentration-dependent manner. Also, cucurbitacin-I induced G2/M phase cell
      cycle arrest in SW480 cells with a decreased expression of cell cycle proteins
      including cyclin B1, cyclin A, CDK1, and CDC25C. Moreover, cucurbitacin-I induced
      increased cleavage of caspase-3, -7, -8, -9, and poly ADP ribose polymerase. When
      we examined the inhibitory effect of cucurbitacin-I on tumor growth in vivo,
      cucurbitacin-I effectively inhibited the tumorigenicity and growth of CT-26 cells
      in syngenic BALB/c mice. In summary, the present study showed that cucurbitacin-I
      reduced colon cancer cell proliferation by enhancing apoptosis and causing cell
      cycle arrest at the G2/M phase. 

PMID- 24858078
TI  - Expression and function of the ACE2/angiotensin(1-7)/Mas axis in osteosarcoma
      cell lines U-2 OS and MNNG-HOS.
AB  - The renin-angiotensin-system (RAS), via its classical angiotensin-converting
      enzyme (ACE)/angiotensin II/angiotensin II type 1 receptor (AT1R)-axis, is
      associated with proliferation and metastasis of numerous types of solid tumor.
      AT1R blockers reduce tumor volume and decrease liver and lung metastasis in
      murine models of osteosarcoma. Expression and function of the alternative
      ACE2/Ang(1-7)/Mas axis in osteosarcoma is yet to be studied. In the present
      study, the basic and interleukin (IL)-1beta-stimulated expression of components
      of this alternative RAS axis were analyzed and the impact of Mas on proliferation
      and/or migration of U-2 OS and MNNG-HOS osteosarcoma cells was studied.
      Quantitative polymerase chain reaction revealed that the two cell lines expressed
      the Ang(1-7)-generating peptidases ACE2, neutral endopeptidase 24.11 and prolyl
      endopeptidase together with the putative receptor for Ang(1-7), Mas. IL-1beta
      provoked an induction of Mas mRNA and protein expression which was associated
      with a reduction of proliferation and migration. By contrast, small interfering
      RNA-mediated knockdown of Mas expression led to increased cell proliferation. In
      conclusion, osteosarcoma cells express a functional active alternative ACE2/Ang(1
      7)/Mas axis. The induction and reinforcement of this axis may be beneficial for
      the treatment of osteosarcoma by reducing growth and preventing cancer
      metastasis. These effects may be achieved directly by the administration of Mas
      agonists or, indirectly, via blocking the classical AngII RAS axis via ACE
      inhibitors or AT1R antagonists. 

PMID- 24858079
TI  - Transcriptional regulation of Mycobacterium tuberculosis hupB gene expression.
AB  - The influence of iron levels on the transcription of the hupB gene in
      Mycobacterium tuberculosis is the focus of this study. Studies in our laboratory
      showed HupB to be co-expressed with the two siderophores in low-iron organisms.
      Mycobactin biosynthesis is repressed by the IdeR-Fe(2+) complex that binds the
      IdeR box in the mbtB promoter. Recently, we demonstrated the positive regulatory
      effect of HupB on mycobactin biosynthesis by demonstrating its binding to a 10 bp
      HupB box in the mbtB promoter. Earlier, we observed that HupB, expressed
      maximally in low-iron media (0.02 ug Fe ml(-1); 0.36 uM Fe) was still detectable
      at 8 ug Fe ml(-1) (144 uM Fe) when the siderophores were absent and complete
      repression was seen only at 12 ug Fe ml(-1) (216 uM Fe). In this study, we
      observed elevated levels of hupB transcripts in iron-limited organisms. IdeR, and
      not FurA, functioned as the iron regulator, by binding to two IdeR boxes in the
      hupB promoter. Interestingly, the 10 bp HupB box, first reported in the mbtB
      promoter, was identified in the hupB promoter. Using DNA footprinting and
      electrophoretic mobility shift assays, we demonstrated the functionality of the
      HupB box and the two IdeR boxes. The high hupB transcript levels expressed by the
      organism and the in vitro protein-DNA interaction studies led us to hypothesize
      the sequence of events occurring in response to changes in the intracellular iron
      concentration, emphasizing the roles played by IdeR and HupB in iron homeostasis.

PMID- 24858081
TI  - SecA defects are accompanied by dysregulation of MukB, DNA gyrase, chromosome
      partitioning and DNA superhelicity in Escherichia coli.
AB  - Spatial regulation of nucleoids and chromosome-partitioning proteins is important
      for proper chromosome partitioning in Escherichia coli. However, the underlying
      molecular mechanisms are unknown. In the present work, we showed that mutation or
      chemical perturbation of secretory A (SecA), an ATPase component of the membrane
      protein translocation machinery, SecY, a component of the membrane protein
      translocation channel and acyl carrier protein P (AcpP), which binds to SecA and
      MukB, a functional homologue of structural maintenance of chromosomes protein
      (SMC), resulted in a defect in chromosome partitioning. We further showed that
      SecA is essential for proper positioning of the oriC DNA region, decatenation and
      maintenance of superhelicity of DNA. Genetic interaction studies revealed that
      the topological abnormality observed in the secA mutant was due to combined
      inhibitory effects of defects in MukB, DNA gyrase and Topo IV, suggesting a role
      for the membrane protein translocation machinery in chromosome partitioning
      and/or structural maintenance of chromosomes. 

PMID- 24858080
TI  - Identification of a Salmonella ancillary copper detoxification mechanism by a
      comparative analysis of the genome-wide transcriptional response to copper and
      zinc excess.
AB  - Copper and zinc are essential metal ions, but toxic in excess. Bacteria have
      evolved different strategies to control their intracellular concentrations,
      ensuring proper supply while avoiding toxicity, including the induction of metal
      specific as well as non-specific mechanisms. We compared the transcriptional
      profiles of Salmonella Typhimurium after exposure to either copper or zinc ions
      in both rich and minimal media. Besides metal-specific regulatory networks many
      global stress-response pathways react to an excess of either of these metal ions.
      Copper excess affects both zinc and iron homeostasis by inducing transcription of
      these metal-specific regulons. In addition to the control of zinc-specific
      regulons, zinc excess affects the Cpx regulon and the sigma(E) envelope-stress
      responses. Finally, novel metal-specific upregulated genes were detected
      including a new copper-detoxification pathway that involves the siderophore
      enterobactin and the outer-membrane protein TolC. This work sheds light onto the
      transcriptional landscape of Salmonella after copper or zinc overload, and
      discloses a new mechanism of copper detoxification. 

PMID- 24858082
TI  - Observation of the time-course for peptidoglycan lipid intermediate II
      polymerization by Staphylococcus aureus monofunctional transglycosylase.
AB  - The polymerization of lipid intermediate II by the transglycosylase activity of
      penicillin-binding proteins (PBPs) represents an important target for
      antibacterial action, but limited methods are available for quantitative assay of
      this reaction, or screening potential inhibitors. A new labelling method for
      lipid II polymerization products using Sanger's reagent (fluoro-2,4
      dinitrobenzene), followed by gel permeation HPLC analysis, has permitted the
      observation of intermediate polymerization products for Staphylococcus aureus
      monofunctional transglycosylase MGT. Peak formation is inhibited by 6 uM
      ramoplanin or enduracidin. Characterization by mass spectrometry indicates the
      formation of tetrasaccharide and octasaccharide intermediates, but not a
      hexasaccharide intermediate, suggesting a dimerization of a lipid-linked
      tetrasaccharide. Numerical modelling of the time-course data supports a kinetic
      model involving addition to lipid-linked tetrasaccharide of either lipid II or
      lipid-linked tetrasaccharide. Observation of free octasaccharide suggests that
      hydrolysis of the undecaprenyl diphosphate lipid carrier occurs at this stage in
      peptidoglycan transglycosylation. 

PMID- 24858083
TI  - The molecular biology of mycobacterial trehalose in the quest for advanced
      tuberculosis therapies.
AB  - Trehalose is a natural glucose disaccharide identified in the 19th century in
      fungi and insect cocoons, and later across the three domains of life. In members
      of the genus Mycobacterium, which includes the tuberculosis (TB) pathogen and
      over 160 species of nontuberculous mycobacteria (NTM), many of which are
      opportunistic pathogens, trehalose has been an important focus of research over
      the last 60 years. It is a crucial player in the assembly and architecture of the
      remarkable mycobacterial cell envelope as an element of unique highly antigenic
      glycolipids, namely trehalose dimycolate ('cord factor'). Free trehalose has been
      detected in the mycobacterial cytoplasm and occasionally in oligosaccharides with
      unknown function. TB and NTM infection statistics and death toll, the decline in
      immune responses in the aging population, human immunodeficiency virus/AIDS or
      other debilitating conditions, and the proliferation of strains with different
      levels of resistance to the dated drugs in use, all merge into a serious public
      health threat urging more effective vaccines, efficient diagnostic tools and new
      drugs. This review deals with the latest findings on mycobacterial trehalose
      biosynthesis, catabolism, processing and recycling, as well with the ongoing
      quest for novel trehalose-related mechanisms to be targeted by novel TB
      therapeutics. In this context, the drug-discovery pipeline has recently included
      new lead compounds directed toward trehalose-related targets highlighting the
      potential of these pathways to stem the tide of rising drug resistance. 

PMID- 24858084
TI  - rpoD gene pyrosequencing for the assessment of Pseudomonas diversity in a water
      sample from the Woluwe River.
AB  - A water sample from a noncontaminated site at the source of the Woluwe River
      (Belgium) was analyzed by culture-dependent and -independent methods. Pseudomonas
      isolates were identified by sequencing and analysis of the rpoD gene.
      Cultureindependent methods consisted of cloning and pyrosequencing of a
      Pseudomonas rpoD amplicon from total DNA extracted from the same sample and
      amplified with selective rpoD gene primers. Among a total of 14,540 reads, 6,228
      corresponded to Pseudomonas rpoD gene sequences by a BLAST analysis in the NCBI
      database. The selection criteria for the reads were sequences longer than 400 bp,
      an average Q40 value greater than 25, and>85% identity with a Pseudomonas
      species. Of the 6,228 Pseudomonas rpoD sequences, 5,345 sequences met the
      established criteria for selection. Sequences were clustered by phylogenetic
      analysis and by use of the QIIME software package. Representative sequences of
      each cluster were assigned by BLAST analysis to a known Pseudomonas species when
      the identity with the type strain was greater than or equal to 96%. Twenty-six
      species distributed among 12 phylogenetic groups or subgroups within the genus
      were detected by pyrosequencing. Pseudomonas stutzeri, P. moraviensis, and P.
      simiae were the only cultured species not detected by pyrosequencing. The
      predominant phylogenetic group within the Pseudomonas genus was the P.
      fluorescens group, as determined by culture-dependent and -independent analyses.
      In all analyses, a high number of putative novel phylospecies was found: 10 were
      identified in the cultured strains and 246 were detected by pyrosequencing,
      indicating that the diversity of Pseudomonas species has not been fully
      described.

PMID- 24858085
TI  - Carbohydrate catabolism in Phaeobacter inhibens DSM 17395, a member of the marine
      roseobacter clade.
AB  - Since genome analysis did not allow unambiguous reconstruction of transport,
      catabolism, and substrate-specific regulation for several important carbohydrates
      in Phaeobacter inhibens DSM 17395, proteomic and metabolomic analyses of N
      acetylglucosamine-, mannitol-, sucrose-, glucose-, and xylose-grown cells were
      carried out to close this knowledge gap. These carbohydrates can pass through the
      outer membrane via porins identified in the outer membrane fraction. For
      transport across the cytoplasmic membrane, carbohydrate-specific ABC transport
      systems were identified. Their coding genes mostly colocalize with the respective
      "catabolic" and "regulatory" genes. The degradation of N-acetylglucosamine
      proceeds via N-acetylglucosamine-6-phosphate and glucosamine-6-phosphate directly
      to fructose-6-phosphate; two of the three enzymes involved were newly predicted
      and identified. Mannitol is catabolized via fructose, sucrose via fructose and
      glucose, glucose via glucose-6-phosphate, and xylose via xylulose-5-phosphate. Of
      the 30 proteins predicted to be involved in uptake, regulation, and degradation,
      28 were identified by proteomics and 19 were assigned to their respective
      functions for the first time. The peripheral degradation pathways feed into the
      Entner-Doudoroff (ED) pathway, which is connected to the lower branch of the
      Embden-Meyerhof-Parnas (EMP) pathway. The enzyme constituents of these pathways
      displayed higher abundances in P. inhibens DSM 17395 cells grown with any of the
      five carbohydrates tested than in succinate-grown cells. Conversely,
      gluconeogenesis is turned on during succinate utilization. While tricarboxylic
      acid (TCA) cycle proteins remained mainly unchanged, the abundance profiles of
      their metabolites reflected the differing growth rates achieved with the
      different substrates tested. Homologs of the 74 genes involved in the
      reconstructed catabolic pathways and central metabolism are present in various
      Roseobacter clade members.

PMID- 24858086
TI  - Metabolic shift of Escherichia coli under salt stress in the presence of glycine
      betaine.
AB  - An important area of food safety focuses on bacterial survival and growth in
      unfavorable environments. In order to understand how bacteria adapt to stresses
      other than nutrient limitation in batch cultures, we need to develop mechanistic
      models of intracellular regulation and metabolism under stress. We studied the
      growth of Escherichia coli in minimal medium with added salt and different
      osmoprotectants. To characterize the metabolic efficiency with a robust
      parameter, we identified the optical density (OD) values at the inflection points
      of measured "OD versus time" growth curves and described them as a function of
      glucose concentration. We found that the metabolic efficiency parameter did not
      necessarily follow the trend of decreasing specific growth rate as the salt
      concentration increased. In the absence of osmoprotectant, or in the presence of
      proline, the metabolic efficiency decreased with increasing NaCl concentration.
      However, in the presence of choline or glycine betaine, it increased between 2
      and 4.5% NaCl before declining at 5% NaCl and above. Microarray analysis of the
      transcriptional network and proteomics analysis with glycine betaine in the
      medium indicated that between 4.5 and 5% NaCl, the metabolism switched from
      aerobic to fermentative pathways and that the response to osmotic stress is
      similar to that for oxidative stress. We conclude that, although the growth rate
      appeared to decrease smoothly with increasing NaCl, the metabolic strategy of
      cells changed abruptly at a threshold concentration of NaCl.

PMID- 24858087
TI  - The temperature gradient-forming device, an accessory unit for normal light
      microscopes to study the biology of hyperthermophilic microorganisms.
AB  - To date, the behavior of hyperthermophilic microorganisms in their biotope has
      been studied only to a limited degree; this is especially true for motility. One
      reason for this lack of knowledge is the requirement for high-temperature
      microscopy-combined, in most cases, with the need for observations under strictly
      anaerobic conditions-for such studies. We have developed a custom-made, low
      budget device that, for the first time, allows analyses in temperature gradients
      up to 40 degrees C over a distance of just 2 cm (a biotope-relevant distance)
      with heating rates up to ~5 degrees C/s. Our temperature gradient-forming device
      can convert any upright light microscope into one that works at temperatures as
      high as 110 degrees C. Data obtained by use of this apparatus show how very well
      hyperthermophiles are adapted to their biotope: they can react within seconds to
      elevated temperatures by starting motility-even after 9 months of storage in the
      cold. Using the temperature gradient-forming device, we determined the
      temperature ranges for swimming, and the swimming speeds, of 15 selected species
      of the genus Thermococcus within a few months, related these findings to the
      presence of cell surface appendages, and obtained the first evidence for
      thermotaxis in Archaea. 

PMID- 24858088
TI  - Simultaneous fermentation of glucose and xylose to butanol by Clostridium sp.
      strain BOH3.
AB  - Cellulose and hemicellulose constitute the major components in sustainable
      feedstocks which could be used as substrates for biofuel generation. However,
      following hydrolysis to monomer sugars, the solventogenic Clostridium will
      preferentially consume glucose due to transcriptional repression of xylose
      utilization genes. This is one of the major barriers in optimizing
      lignocellulosic hydrolysates that produce butanol. Unlike studies on existing
      bacteria, this study demonstrates that newly reported Clostridium sp. strain BOH3
      is capable of fermenting 60 g/liter of xylose to 14.9 g/liter butanol, which is
      similar to the 14.5 g/liter butanol produced from 60 g/liter of glucose. More
      importantly, strain BOH3 consumes glucose and xylose simultaneously, which is
      shown by its capability for generating 11.7 g/liter butanol from a horticultural
      waste cellulosic hydrolysate containing 39.8 g/liter glucose and 20.5 g/liter
      xylose, as well as producing 11.9 g/liter butanol from another horticultural
      waste hemicellulosic hydrolysate containing 58.3 g/liter xylose and 5.9 g/liter
      glucose. The high-xylose-utilization capability of strain BOH3 is attributed to
      its high xylose-isomerase (0.97 U/mg protein) and xylulokinase (1.16 U/mg
      protein) activities compared to the low-xylose-utilizing solventogenic strains,
      such as Clostridium sp. strain G117. Interestingly, strain BOH3 was also found to
      produce riboflavin at 110.5 mg/liter from xylose and 76.8 mg/liter from glucose
      during the fermentation process. In summary, Clostridium sp. strain BOH3 is an
      attractive candidate for application in efficiently converting lignocellulosic
      hydrolysates to biofuels and other value-added products, such as riboflavin. 

PMID- 24858091
TI  - Reconstructive urology and the cancer survivor.

PMID- 24858089
TI  - Genetic diversity and virulence potential of shiga toxin-producing Escherichia
      coli O113:H21 strains isolated from clinical, environmental, and food sources.
AB  - Shiga toxin-producing Escherichia coli strains of serotype O113:H21 have caused
      severe human diseases, but they are unusual in that they do not produce adherence
      factors coded by the locus of enterocyte effacement. Here, a PCR microarray was
      used to characterize 65 O113:H21 strains isolated from the environment, food, and
      clinical infections from various countries. In comparison to the pathogenic
      strains that were implicated in hemolytic-uremic syndrome in Australia, there
      were no clear differences between the pathogens and the environmental strains
      with respect to the 41 genetic markers tested. Furthermore, all of the strains
      carried only Shiga toxin subtypes associated with human infections, suggesting
      that the environmental strains have the potential to cause disease. Most of the
      O113:H21 strains were closely related and belonged in the same clonal group (ST
      223), but CRISPR analysis showed a great degree of genetic diversity among the
      O113:H21 strains. 

PMID- 24858090
TI  - Fusion of self-assembling amphipathic oligopeptides with cyclodextrin
      glycosyltransferase improves 2-O-D-glucopyranosyl-L-ascorbic acid synthesis with
      soluble starch as the glycosyl donor.
AB  - In this study, we fused six self-assembling amphipathic peptides (SAPs) with
      cyclodextrin glycosyltransferase (CGTase) from Paenibacillus macerans to catalyze
      2-O-D-glucopyranosyl-L-ascorbic acid (AA-2G) production with cheap substrates,
      including maltose, maltodextrin, and soluble starch as glycosyl donors. The
      results showed that two fusion enzymes, SAP5-CGTase and SAP6-CGTase, increased AA
      2G yields to 2.33- and 3.36-fold that of wild-type CGTase when soluble starch was
      used as a substrate. The cyclization activities of these enzymes decreased, while
      disproportionation activities increased. Enzymatic characterization of the two
      fusion enzymes was performed, and kinetics analysis of AA-2G synthesis confirmed
      the enhanced soluble starch specificity of SAP5-CGTase and SAP6-CGTase compared
      to that in the wild-type CGTase. As revealed by structure modeling of the fusion
      and wild-type CGTases, enhanced substrate-binding capacity may result from the
      increased number of hydrogen bonds present after fusion. This study demonstrates
      an effective protein fusion approach to improving the substrate specificity of
      CGTase for AA-2G synthesis. Fusion enzymes, especially SAP6-CGTase, are promising
      starting points for further development through protein engineering.

PMID- 24858092
TI  - Intermittent contact resonance atomic force microscopy.
AB  - The intermittent contact resonance atomic force microscopy (ICR-AFM) mode
      proposed here is a new frequency modulation technique performed in scanning force
      controlled AFM modes like force volume or peak force tapping. It consists of
      tracking the change in the resonance frequency of an eigenmode of a driven AFM
      cantilever during scanning as the AFM probe intermittently contacts a surface at
      a controlled applied maximum force (setpoint). A high speed data capture was used
      during individual oscillations to obtain detailed contact stiffness-force curve
      measurements on a two-phase polystyrene/poly(methyl methacrylate) film with sub
      micrometer size domains. Through a suitable normalization, the measurements were
      analyzed by linear fits to provide an improved quantitative characterization of
      these materials in terms of their elastic moduli and adhesive properties.

PMID- 24858093
TI  - Berberine enhances the antibacterial activity of selected antibiotics against
      coagulase-negative Staphylococcus strains in vitro.
AB  - Synergistic interactions between commonly used antibiotics and natural bioactive
      compounds may exhibit therapeutic benefits in a clinical setting. Berberine, an
      isoquinoline-type alkaloid isolated from many kinds of medicinal plants, has
      proven efficacy against a broad spectrum of microorganisms. The aim of the
      presented work was to assess the antibacterial activity of berberine chloride in
      light of the effect exerted by common antibiotics on fourteen reference strains
      of Staphylococccus spp., and to evaluate the magnitude of interactions of
      berberine with these antistaphylococcal antibiotics. In our study minimum
      inhibitory concentrations (MIC) of berberine chloride against CoNS ranged from 16
      to 512 ug/mL. The most noticeable effects were observed for S. haemolyticus ATCC
      29970, S. epidermidis ATCC 12228, S. capitis subsp. capitis ATCC 35661, S.
      galinarium ATCC 700401, S. hominis subsp. hominis ATCC 27844, S. intermedius ATCC
      29663 and S. lugdunensis ATCC 49576. The most significant synergistic effect was
      noticed for berberine in combination with linezolid, cefoxitin and erythromycin.
      The synergy between berberine and antibiotics demonstrates the potential
      application of compound combinations as an efficient, novel therapeutic tool for
      antibiotic-resistant bacterial infections. 

PMID- 24858094
TI  - Bioactive secondary metabolites from Phomopsis sp., an endophytic fungus from
      Senna spectabilis.
AB  - Chemical investigation of an acetonitrile fraction from the endophytic fungus
      Phomopsis sp. led to the isolation of the new natural product 2-hydroxy
      alternariol (7) together with the known compounds cytochalasins J (1) and H (2),
      5'-epialtenuene (3) and the mycotoxins alternariol monomethyl ether (AME, 4),
      alternariol (AOH, 5) and cytosporone C (6). The structure of the new compound was
      elucidated by using 1-D and 2-D NMR (nuclear magnetic resonance) and high
      resolution mass spectrometry. The cytochalasins J (1) and H (2) and AOH (5)
      exhibited potent inhibition of the total ROS (reactive oxygen species) produced
      by stimulated human neutrophils and acted as potent potential anti-inflammatory
      agents. Moreover, cytochalasin H (2) demonstrated antifungal and
      acetylcholinesterase enzyme (AChE) inhibition in vitro. 

PMID- 24858095
TI  - In silico docking, molecular dynamics and binding energy insights into the
      bolinaquinone-clathrin terminal domain binding site.
AB  - Clathrin-mediated endocytosis (CME) is a process that regulates selective
      internalization of important cellular cargo using clathrin-coated vesicles.
      Perturbation of this process has been linked to many diseases including cancer
      and neurodegenerative conditions. Chemical proteomics identified the marine
      metabolite, 2-hydroxy-5-methoxy-3-(((1S,4aS,8aS)-1,4a,5-trimethyl
      1,2,3,4,4a,7,8,8a-octahydronaphthalen-2-yl)methyl)cyclohexa- 2,5-diene-1,4-dione
      (bolinaquinone) as a clathrin inhibitor. While being an attractive medicinal
      chemistry target, the lack of data about bolinaquinone's mode of binding to the
      clathrin enzyme represents a major limitation for its structural optimization. We
      have used a molecular modeling approach to rationalize the observed activity of
      bolinaquinone and to predict its mode of binding with the clathrin terminal
      domain (CTD). The applied protocol started by global rigid-protein docking
      followed by flexible docking, molecular dynamics and linear interaction energy
      calculations. The results revealed the potential of bolinaquinone to interact
      with various pockets within the CTD, including the clathrin-box binding site. The
      results also highlight the importance of electrostatic contacts over van der
      Waals interactions for proper binding between bolinaquinone and its possible
      binding sites. This study provides a novel model that has the potential to allow
      rapid elaboration of bolinaquinone analogues as a new class of clathrin
      inhibitors. 

PMID- 24858096
TI  - New flavanol and cycloartane glucosides from Landoltia punctata.
AB  - Chemical investigation on the constituents of Landoltia punctata led to the
      isolation and identification of 17 compounds, four of which were new and
      identified as (3b,24S)-9,19-cycloartane-3,22,24,25-tetraol 3-O-[b-D
      glucopyranosyl-(1->2)]-[b-D-glucopyranosyl-(1->6)]-b-D-glucopyranoside (1),
      (3b,24S)-9,19-cycloartane-3,24,25-triol 3-O-[b-d-glucopyranosyl-(1->2)]-[b-D
      glucopyranosyl-(1->6)]-b-D-glucopyranoside (2), 3,4'-dihydroxy-7,3'
      dimethoxyflavan-5-O-b-D-glucopyranoside (3) and 3,4'-dihydroxy-4,7,3'
      trimethoxyflavan-5-O-b-D-glucopyranoside (4). Their structures were elucidated by
      spectroscopic, chemical, and biochemical methods. Thus, cycloartane triterpenoids
      were discovered in the Lemnaceae family for the first time. Compound 3 showed
      antioxidant capacity in the positively charged 2,2'-azino-bis-3
      ethylbenzothiazoline-6-sulfonic acid radical (ABTS+*) and superoxide anion
      radical scavenging assays. 

PMID- 24858097
TI  - A novel aqueous two phase system composed of a thermo-separating polymer and an
      organic solvent for purification of thermo-acidic amylase enzyme from red pitaya
      (Hylocereus polyrhizus) peel.
AB  - The purification of thermo-acidic amylase enzyme from red pitaya (Hylocereus
      polyrhizus) peel for the first time was investigated using a novel aqueous two
      phase system (ATPS) consisting of a thermo-separating copolymer and an organic
      solvent. The effectiveness of different parameters such as molecular weight of
      the thermo-separating ethylene oxide-propylene oxide (EOPO) copolymer and type
      and concentration of organic solvent on the partitioning behavior of amylase was
      investigated. In addition, the effects of phase components, volume ratio (VR), pH
      and crude load of purification factor and yield of amylase were evaluated to
      achieve the optimum partition conditions of the enzyme. In the novel ATPS method,
      the enzyme was satisfactorily partitioned into the polymer-rich top phase in the
      system composed of 30% (w/w) EOPO 2500 and 15% (w/w) 2-propanol, at a volume
      ratio of 1.94 and with a crude load scale of 25% (w/w) at pH 5.0. Recovery and
      recycling of components was also measured in each successive step of the ATPS
      process. The enzyme was successfully recovered by the method with a high
      purification factor of 14.3 and yield of 96.6% and copolymer was also recovered
      and recycled at a rate above 97%, making the method was more economical than the
      traditional ATPS method. 

PMID- 24858098
TI  - Synthesis, cytotoxicity and mechanistic evaluation of 4-oxoquinoline-3
      carboxamide derivatives: finding new potential anticancer drugs.
AB  - As part of a continuing search for new potential anticancer candidates, we
      describe the synthesis, cytotoxicity and mechanistic evaluation of a series of 4
      oxoquinoline-3-carboxamide derivatives as novel anticancer agents. The inhibitory
      activity of compounds 10-18 was determined against three cancer cell lines using
      the MTT colorimetric assay. The screening revealed that derivatives 16b and 17b
      exhibited significant cytotoxic activity against the gastric cancer cell line but
      was not active against a normal cell line, in contrast to doxorubicin, a standard
      chemotherapeutic drug in clinical use. Interestingly, no hemolytical activity was
      observed when the toxicity of 16b and 17b was tested against blood cells. The in
      silico and in vitro mechanistic evaluation indicated the potential of 16b as a
      lead for the development of novel anticancer agents against gastric cancer cells.

PMID- 24858099
TI  - Synthesis and antiproliferative effects of amino-modified perillyl alcohol
      derivatives.
AB  - Two series of amino-modified derivatives of (S)-perillyl alcohol were designed
      and synthesized using (S)-perillaldehyde as the starting material. These
      derivatives showed increased antiproliferative activity in human lung cancer A549
      cells, human melanoma A375-S2 cells and human fibrosarcoma HT-1080 cells
      comparing with that of (S)-perillyl alcohol. Among these derivatives, compounds
      VI5 and VI7 were the most potent agents, with the IC50s below 100 MUM. It was
      demonstrated that the antiproliferative effect of VI5 was mediated through the
      induction of apoptosis in A549 cells. 

PMID- 24858100
TI  - Direct 2,3-O-isopropylidenation of alpha-D-mannopyranosides and the preparation
      of 3,6-branched mannose trisaccharides.
AB  - A highly efficient, regioselective method for the direct 2,3-O-isopropylidenation
      of alpha-D-mannopyranosides is reported. Treatment of various alpha-D
      mannopyranosides with 0.12 equiv of the TsOH.H2O and 2-methoxypropene at 70 
      degrees C gave 2,3-O-isopropylidene-alpha-D-mannopyranosides directly in 80%~90%
      yields. Based on this method, a 3,6-branched alpha-D-mannosyl trisaccharide was
      prepared in 50.4% total yield using p-nitrophenyl 2,3-O-isopropylidene-alpha-D
      mannopyranoside as the starting material. 

PMID- 24858101
TI  - Linalool exhibits cytotoxic effects by activating antitumor immunity.
AB  - According to recent studies, the Plantaginaceae, which are traditional Chinese
      herbal remedies, have potential for use in viral infection treatment and cancer
      therapy. Linalool and p-coumaric acid are two of the biologically active
      compounds that can be isolated from the Plantaginaceae. This study mainly focused
      on investigating the bioactivity of linalool as well as the bioactivity of p
      coumaric acid in terms of their cytotoxic effects on cancer cells. Whether the
      mechanisms of such effects are generated through apoptosis and immunoregulatory
      activity were also investigated. By using WST-1 analysis, it was shown that
      linalool and p-coumaric acid have good inhibitory effects against breast,
      colorectal and liver cancer cells. The IC50 values of linalool for those cancer
      cell types were 224 MUM, 222 MUM, and 290 MUM, respectively, and the IC50 values
      of p-coumaric acid were 693 MUM, 215 MUM and 87 MUM, respectively. Cell cycle
      analysis also confirmed that linalool and p-coumaric acid can lead to apoptosis.
      By using flow cytometry, it was determined that treatment with linalool rather
      than p-coumaric acid significantly increased the sub-G1 phase and that there were
      more cells concentrated in the G1 phase. Furthermore, by using cytokine array
      analysis, we found that linalool can stimulate IFN-gamma, IL-13, IL-2, IL-21, IL
      21R, IL-4, IL-6sR and TNF-alpha secretion. This demonstrated that in addition to
      the bidirectional regulation capabilities found in linalool, it also induces Th1
      cellular immune response in T-47D cells. These results showed that linalool holds
      great potential for use in cancer therapy, and we believe that it could provide
      an alternative way to take action against tumors. 

PMID- 24858102
TI  - Role of oligomeric proanthocyanidins derived from an extract of persimmon fruits
      in the oxidative stress-related aging process.
AB  - Many researchers have focused on the oligomeric form of proanthocyanidins with a
      lower level of polymerization found in foodstuffs such as grape seeds and
      blackberries. The present study indicated that the oral administration of
      oligomers isolated from persimmon fruits extended the lifespan of senescence
      accelerated mouse prone/8 (SAMP8), a murine model of accelerated senescence. On
      the other hand, oligomer-treated SAMP8 did not show stereotypical behavior. We
      also revealed that the oral administration of oligomers improved spatial and
      object recognition memory in SAMP8. The density of axons in the hippocampal CA1
      was significantly increased by oligomer administration. Moreover, the
      administration of oligomers increased the phosphorylation of vascular endothelial
      growth factor receptor (VEGFR)-2 in the hippocampal CA3, hypothalamus, and
      choroid plexus. We speculate that memory improvement accompanied by histological
      changes may be induced directly in the hippocampus and indirectly in the
      hypothalamus and choroid plexus through VEGFR-2 signaling. In the present study,
      we elucidated the protective effect of oligomers against memory impairment with
      aging. VEGFR-2 signaling may provide a new insight into ways to protect against
      memory deficit in the aging brain. 

PMID- 24858103
TI  - Four new flavonol glycosides from the leaves of Brugmansia suaveolens.
AB  - Four new flavonol glycosides were isolated from the leaves of Brugmansia
      suaveolens: kaempferol 3-O-beta-D-glucopyranosyl-(1'''->2'')-O-alpha-L
      arabinopyranoside (1), kaempferol 3-O-beta-D-glucopyranosyl-(1'''->2'')-O-alpha-L
      arabinopyranoside-7-O-i-D-gluco-pyranoside (2), kaempferol 3-O-beta-D-[6'''-O-(E
      caffeoyl)]-glucopyranosyl-(1'''->2'')-O-alpha-l-arabinopyranoside-7-O-beta-D
      glucopyranoside (3), and kaempferol 3-O-beta-D-[2'''-O-(E-caffeoyl)]
      glucopyranosyl-(1'''->2'')-O-alpha-l-arabinopyranoside-7-O-beta-D-glucopyranoside
      (4). The structure elucidation was performed by MS, 1D and 2D NMR analyses. 

PMID- 24858106
TI  - The effects of relational structure on analogical learning.
AB  - Relational structure is important for various cognitive tasks, such as analogical
      transfer, but its role in learning of new relational concepts is poorly
      understood. This article reports two experiments testing people's ability to
      learn new relational categories as a function of their relational structure. In
      Experiment 1, each stimulus consisted of 4 objects varying on 2 dimensions. Each
      category was defined by two binary relations between pairs of objects. The manner
      in which the relations were linked (i.e., by operating on shared objects) varied
      between subjects, producing 3 logically different conditions. In Experiment 2,
      each stimulus consisted of 4 objects varying on 3 dimensions. Categories were
      defined by three binary relations, leading to six logically different conditions.
      Various learning models were compared to the behavioral data, based on the theory
      of schema refinement. The results highlight several shortcomings of schema
      refinement as a model of relational learning: (1) it can make unreasonable
      demands on working memory, (2) it does not allow schemas to grow in complexity,
      and (3) it incorrectly predicts learning is insensitive to relational structure.
      We propose schema elaboration as an additional mechanism that provides a more
      complete account, and we relate this mechanism to previous proposals regarding
      interactions between analogy and representation construction. The current
      findings may advance understanding of the cognitive mechanisms involved in
      learning and representing relational concepts. 

PMID- 24858105
TI  - Integrated proteomics identified up-regulated focal adhesion-mediated proteins in
      human squamous cell carcinoma in an orthotopic murine model.
AB  - Understanding the molecular mechanisms of oral carcinogenesis will yield
      important advances in diagnostics, prognostics, effective treatment, and outcome
      of oral cancer. Hence, in this study we have investigated the proteomic and
      peptidomic profiles by combining an orthotopic murine model of oral squamous cell
      carcinoma (OSCC), mass spectrometry-based proteomics and biological network
      analysis. Our results indicated the up-regulation of proteins involved in actin
      cytoskeleton organization and cell-cell junction assembly events and their
      expression was validated in human OSCC tissues. In addition, the functional
      relevance of talin-1 in OSCC adhesion, migration and invasion was demonstrated.
      Taken together, this study identified specific processes deregulated in oral
      cancer and provided novel refined OSCC-targeting molecules. 

PMID- 24858107
TI  - The role of the input on the development of the LC bias: a crosslinguistic
      comparison.
AB  - Previous studies have described the existence of a phonotactic bias called the
      Labial-Coronal (LC) bias, corresponding to a tendency to produce more words
      beginning with a labial consonant followed by a coronal consonant (i.e. "bat")
      than the opposite CL pattern (i.e. "tap"). This bias has initially been
      interpreted in terms of articulatory constraints of the human speech production
      system. However, more recently, it has been suggested that this presumably
      language-general LC bias in production might be accompanied by LC and CL biases
      in perception, acquired in infancy on the basis of the properties of the
      linguistic input. The present study investigates the origins of these perceptual
      biases, testing infants learning Japanese, a language that has been claimed to
      possess more CL than LC sequences, and comparing them with infants learning
      French, a language showing a clear LC bias in its lexicon. First, a corpus
      analysis of Japanese IDS and ADS revealed the existence of an overall LC bias,
      except for plosive sequences in ADS, which show a CL bias across counts. Second,
      speech preference experiments showed a perceptual preference for CL over LC
      plosive sequences (all recorded by a Japanese speaker) in 13- but not in 7- and
      10-month-old Japanese-learning infants (Experiment 1), while revealing the
      emergence of an LC preference between 7 and 10 months in French-learning infants,
      using the exact same stimuli. These crosslinguistic behavioral differences,
      obtained with the same stimuli, thus reflect differences in processing in two
      populations of infants, which can be linked to differences in the properties of
      the lexicons of their respective native languages. These findings establish that
      the emergence of a CL/LC bias is related to exposure to a linguistic input. 

PMID- 24858108
TI  - Hearing brighter: changing in-depth visual perception through looming sounds.
AB  - Rapidly approaching (looming) sounds are ecologically salient stimuli that are
      perceived as nearer than they are due to overestimation of their loudness change
      and underestimation of their distance (Neuhoff, 1998; Seifritz et al., 2002).
      Despite evidence for crossmodal influence by looming sounds onto visual areas
      (Romei, Murray, Cappe, & Thut, 2009, 2013; Tyll et al., 2013), it is unknown
      whether such sounds bias visual percepts in similar ways. Nearer objects appear
      to be larger and brighter than distant objects. If looming sounds impact visual
      processing, then visual stimuli paired with looming sounds should be perceived as
      brighter and larger, even when the visual stimuli do not provide motion cues,
      i.e. are static. In Experiment 1 we found that static visual objects paired with
      looming tones (but not static or receding tones) were perceived as larger and
      brighter than their actual physical properties, as if they appear closer to the
      observer. In a second experiment, we replicate and extend the findings of
      Experiment 1. Crucially, we did not find evidence of such bias by looming sounds
      when visual processing was disrupted via masking or when catch trials were
      presented, ruling out simple response bias. Finally, in a third experiment we
      found that looming tones do not bias visual stimulus characteristics that do not
      carry visual depth information such as shape, providing further evidence that
      they specifically impact in-depth visual processing. We conclude that looming
      sounds impact visual perception through a mechanism transferring in-depth sound
      motion information onto the relevant in-depth visual dimensions (such as size and
      luminance but not shape) in a crossmodal remapping of information for a genuine,
      evolutionary advantage in stimulus detection. 

PMID- 24858109
TI  - Home medical care.

PMID- 24858110
TI  - Freilty: overview and relationships with nutritional issues.

PMID- 24858111
TI  - Locomotive syndrome.

PMID- 24858112
TI  - Dementia manifests in everyday life.

PMID- 24858113
TI  - The role of integrative medicine and Kampo treatment in an aging society:
      experience with Kampo treatment during a natural disaster.
AB  - BACKGROUND AND OBJECTIVES: After the Great East Japan Earthquake, elderly
      individuals, who are particularly vulnerable during natural disasters,
      experienced difficulty while evacuating the area. This report discusses the Kampo
      treatments provided to elderly individuals in the disaster areas, and the role of
      integrative medicine and Kampo treatment. METHODS: The changes in symptoms and
      Kampo treatment contents were summarized using the medical records of treatments
      provided in the evacuation centers until 10 weeks after the earthquake. RESULTS:
      Infectious diseases, the common cold and hypothermia were frequently observed in
      most patients for first two weeks after the disaster. Allergies increased two
      weeks later, and mental distress was commonly observed six weeks later. We
      prescribed several Kampo formulas to treat the individual symptoms. DISCUSSION:
      Many elderly individuals were treated using Western medications, but the symptoms
      persisted; however, after Kampo formulas were included in the treatment, the
      symptoms of many patients improved. Unlike Western medications, Kampo formulas
      warmed the bodies of elderly individuals who often had a reduced basal metabolism
      and low body temperatures due to exposure to the cold tsunami waters. Therefore,
      the Kampo formulas may have improved the immunity of those who were under
      psychological and physical stress because they had spent several days in the
      evacuation centers. CONCLUSION: Many studies have reported the effectiveness of
      Kampo formulas. Therefore, the combined usage of both Western and Kampo medicine
      may be used in a mutually complementary manner, and these combination treatments
      may play an important role in preserving the victims overall health after natural
      disasters.

PMID- 24858114
TI  - Role of acupuncture and moxibustion in medical care for the elderly.

PMID- 24858115
TI  - Holistic health, medicine and care for elder generation ~Development at holistic
      health plaza kagoshima~.

PMID- 24858116
TI  - Dietary therapy for the elderly.

PMID- 24858117
TI  - Prospects for the appropriate use of the dietary supplements in geriatric
      medicine.

PMID- 24858118
TI  - Average and healthy life expectancies and self-rated health in the European
      country.
AB  - AIM: When considering the health of elderly individuals, extending a healthy
      lifespan as well as the average life expectancy has been discussed. In general,
      life expectancy is determined by biological health, socioeconomic factor, and
      social disparities. However, the effects of fatal diseases, such as cancer,
      socioeconomic factor, and self-rated health on the average life expectancy and
      healthy life expectancy have not been fully elucidated. METHODS: In the present
      study, a multiple regression analysis was used to clarify the relationships
      between the lifespan and socio-economic conditions, such as the GDP, GiNi index,
      age-adjusted mortality from cancer, suicide rate and self-rated health in 27
      European countries. RESULTS: According to the multiple regression analysis, the
      average life expectancy was significantly correlated with mortality from cancer
      (beta=-0.816, P=0.001), whereas the healthy life expectancy was significantly
      correlated with self-rated health (beta=0.759, p=0.001) in males. In females, the
      average life expectancy was significantly correlated with mortality from cancer
      (beta=-0.470, p=0.004), whereas the healthy life expectancy was significantly
      correlated with self-rated health (beta=0.605, p=0.001). CONCLUSIONS: These
      findings indicate that there is a significant correlation between cancer and life
      expectancy. Meanwhile, self-rated health is an important factor for increasing
      the longevity of a healthy life expectancy.

PMID- 24858119
TI  - Clinical usefulness of indoor life-space assessment in community-dwelling older
      adults certified as needing support or care.
AB  - PURPOSE: This study aimed to develop a questionnaire to evaluate indoor life
      space mobility and assess its validity in community-dwelling older adults
      certified as needing support or care. METHODS: The participants included 37
      community-dwelling older adults undergoing home-visit rehabilitation (mean age:
      78.5+/-7.0 years). We developed a questionnaire to assess the degree of indoor
      life-space mobility (home-based life-space assessment (Hb-LSA)), evaluating the
      functional status (life-space assessment (LSA), time spent away from bed,
      functional independence measure (FIM), bedside mobility scale (BMS)), physical
      function (hand grip power (HGP), 30-second chair stand (CS-30), one-leg standing
      (OLS)) and cognitive status (mental status questionnaire (MSQ)). RESULTS: The
      average Hb-LSA score was 56.3+/-24.3 (minimum 4 to maximum 102.5). The test
      retest reliability was high (intraclass correlation coefficients: (1, 1)=0.986,
      (1, 2)=0.993). The Hb-LSA scores were significantly associated with the LSA
      (r=0.897), time spent away from bed (r=0.497), FIM (r=0.786), BMS (r=0.720), HGP
      (r=0.388), CS-30 (r=0.541) and OLS (r=0.455). There were no significant
      associations between the Hb-LSA scores and the FIM cognitive subscores (r=0.180)
      or MSQ scores (r=-0.240). The Hb-LSA scores were significantly higher among the
      participants able to move independently indoors (75.8+/-18.8 points) than in
      those who required help to move (45.7+/-20.2 points). CONCLUSIONS: The Hb-LSA is
      a useful, reliable and valid tool for assessing the degree of indoor physical
      mobility in the life-space. The Hb-LSA score is related to the degree of
      independence of indoor mobility.

PMID- 24858120
TI  - Development and usefulness of a new questionnaire for assessing geriatric
      syndrome.
AB  - AIM: To assess the validity and reliability of a pre-visit questionnaire newly
      developed to identify geriatric conditions in older adults in an outpatient
      clinical setting. METHODS: A new self-administered questionnaire consisting of 17
      items was distributed to 277 patients or their caregivers visiting a memory
      clinic. The questionnaire was designed to address common symptoms associated with
      an increasing age based on yes/no responses with symptom-oriented questions
      avoiding the use of 'jargon'. The patients also underwent comprehensive geriatric
      assessments (CGAs), as well as tests of the Barthel index, Lawton instrumental
      activities of daily living, mini-mental state examination (MMSE), geriatric
      depression scale and vitality index to assess construct validity in a factor
      analysis. The differences in the prevalence of symptoms between the patients and
      their caregivers were also assessed. RESULTS: The factor analysis detected eight
      components that included symptoms referring to gait disturbance, numbness,
      urinary incontinence, insomnia or body weight loss and were significantly
      correlated with the measurements of the CGA. Cronbach's alpha coefficient for the
      internal consistency of the questionnaire was 0.729. The caregivers tended to
      respond to the questionnaire for older patients (81.6+/-5.5 vs. 76+/-9.7 years of
      age for patients with caregivers as responders versus patients as responders
      respectively, p<0.001) and those with lower MMSE scores (19.4+/-5.8 vs. 24.8+/
      4.2 points, p<0.001). A higher prevalence of falls and episodes of delusions was
      observed among the patients with caregivers as responders. CONCLUSIONS: These
      results demonstrate that the current questionnaire is a valid and reliable
      instrument for use in clinical practice and that obtaining collateral source
      information is essential for assessing significant geriatric symptoms. Such
      information also provides clinicians with a guide to conducting more detailed
      evaluations of geriatric conditions and aids in the diagnostic process in older
      patients with multidisciplinary complications.

PMID- 24858121
TI  - Evaluation of multimodal factors for the certification of long-term care
      insurance among community-dwelling elderly: a four-year follow-up study.
AB  - AIM: The aim of this study was to examine risk factors for the certification of
      long-term care insurance (hereafter reffered to as "certification") in the
      community-dwelling elderly individuals. METHODS: At baseline, 4,503 community
      dwelling elderly responded to a self-completed questionnaires including items for
      "certification". Among the respondents, we analyzed 4,213 individuals with a non
      support status who provided data regarding sex. The endpoint was the onset of
      "certification". At the end of the four-year follow-up period, 313 subjects had
      received "certification" (support-transition group), while the remaining 3,639
      subjects continued to exhibit a non-support status (non-support group). RESULTS:
      The support-transition group contained a higher proposion of subjects with
      chronic disease than the non-support group. The presence of chronic disease, a
      poor condition of the eyes or teeth, infrequent medical checkups, a high BMI,
      changes in body weight within one year, sleep disturbances, poor appetite,
      impaired ambulation, a slow speed while walking and a history of fall(s) within
      the previous one year were found to be significantly related to an increased risk
      of "certification". These items differed between men and women. CONCLUSION: This
      longitudinal study demonstrated that risk factors related to "certification"
      among community-dwelling elderly are multimodal and differ between men and women.
      The presence of chronic disease, the level of health management and the ability
      to engage in physical activity at baseline exhibited significant correlations
      with the need for "certification" over the four-year study period.

PMID- 24858122
TI  - Ideal combination of dementia screening tests.
AB  - AIM: Although many neuropsychological tests have been developed to evaluate
      higher brain dysfunction, conducting several tests in daily medical care is very
      difficult for both the patient and the examiner. We herein reviewed the
      correlation between the results of 11 neuropsychological tests in order to create
      a new compact and easily administered combination of screening tests to detect
      dementia. METHODS: We performed 11 neuropsychological tests in 1,674 outpatients
      suspected of having cognitive dysfunction and 46 normal control subjects. The 11
      tests included the following examinations: the mini mental state examination
      (MMSE) and Hasegawa dementia rating scale-revised (HDS-R) for the total
      intelligence function, the frontal assessment battery (FAB) and Montreal
      cognitive assessment (MoCA) for the frontal lobe function, the neuropsychiatric
      inventory (NPI) and Abe's behavioral and psychological symptoms of dementia score
      (ABS) for emotional changes, the geriatric depression scale (GDS) for depressive
      conditions, the vitality index (VI) and apathy score (AS) for reduced motivation
      and the clinical dementia rating (CDR) and Alzheimer's disease cooperative study
      activities of daily living (ADCS-ADL) scale for ADL's. In order to determine the
      most compact test series, we compared all test features, correlations between the
      scores and the time required to complete each test. RESULTS: Correlations were
      found between tests of the cognitive function, tests of the cognitive function vs
      NPI, tests of the cognitive function vs ADL, NPI vs ABS, NPI vs GDS, GDS vs AS,
      VI vs AS and CDR vs ADCS-ADL. The duration of testing was shorter for the FAB
      than for the MoCA and for the ABS than for the NPI. CONCLUSIONS: A combination of
      six tests (MMSE or HDS-R, FAB, ABS, GDS, AS and ADCS-ADL) was found to be useful
      for screening dementia and reducing the test burden on the patient in daily
      medical practice.

PMID- 24858123
TI  - Effects of bright light exposure on the behavioral and psychological symptoms of
      dementia and the burden on caregivers in institutionalized elderly with cognitive
      decline.
AB  - AIM: The purpose of this study was to examine the effects of bright light
      exposure on behavioral and psychological symptoms of dementia (BPSD), including
      sleep disturbances and the burden on caregivers in institutionalized elderly with
      cognitive decline. METHODS: The subjects included eight people with cognitive
      decline (mean [SD] age, 79.9 [9.1] years) living in geriatric healthcare
      facilities for the elderly. BPSD and the burden on caregivers were measured over
      three weeks using the CMAI (Cohen-Mansfield Agitation Inventory), NPI-NH
      (Neuropsychiatric Inventory-Nursing Home Version) and J-ZBI (Modified Japanese
      Version of the Zarit Caregiver Burden Interview) at the end of each week. During
      the second week, the subjects received either 12,000 K (white) or 2,400 K
      (orange) of light corresponding to approximately 2,000 lux from a light-emitting
      diode (LED) device, measured before the eyes in the gaze direction, from 9 : 00
      to 9 : 30 during occupational tasks, such as origami and coloring. Differences in
      the variables obtained at the different weeks were assessed using ANOVA with
      multiple comparisons. RESULTS: The scores for the severity of BPSD, including
      sleep disturbances and the burden on caregivers, on the NPI-NH significantly
      (P<0.05) improved following the treatment with white light exposure, while the
      scores for the MMSE and J-ZBI did not change over the three-week study period.
      CONCLUSIONS: These results suggest that exposure to white bright light during
      occupational tasks in the morning may have a benefit in improving BPSD, including
      sleep disturbances and the burden on caregivers.

PMID- 24858124
TI  - Educational effects of end-of-life care education program for caring staff of
      long-term care facilities.

PMID- 24858125
TI  - Difficulties in care management felt by care managers.

PMID- 24858129
TI  - Molecular basis of impaired glycogen metabolism during ischemic stroke and
      hypoxia.
AB  - BACKGROUND: Ischemic stroke is the combinatorial effect of many pathological
      processes including the loss of energy supplies, excessive intracellular calcium
      accumulation, oxidative stress, and inflammatory responses. The brain's ability
      to maintain energy demand through this process involves metabolism of glycogen,
      which is critical for release of stored glucose. However, regulation of glycogen
      metabolism in ischemic stroke remains unknown. In the present study, we
      investigate the role and regulation of glycogen metabolizing enzymes and their
      effects on the fate of glycogen during ischemic stroke. RESULTS: Ischemic stroke
      was induced in rats by peri-vascular application of the vasoconstrictor
      endothelin-1 and forebrains were collected at 1, 3, 6 and 24 hours post-stroke.
      Glycogen levels and the expression and activity of enzymes involved in glycogen
      metabolism were analyzed. We found elevated glycogen levels in the ipsilateral
      hemispheres compared with contralateral hemispheres at 6 and 24 hours (25% and
      39% increase respectively; P<0.05). Glycogen synthase activity and glycogen
      branching enzyme expression were found to be similar between the ipsilateral,
      contralateral, and sham control hemispheres. In contrast, the rate-limiting
      enzyme for glycogen breakdown, glycogen phosphorylase, had 58% lower activity
      (P<0.01) in the ipsilateral hemisphere (24 hours post-stroke), which corresponded
      with a 48% reduction in cAMP-dependent protein kinase A (PKA) activity (P<0.01).
      In addition, glycogen debranching enzyme expression 24 hours post-stroke was 77%
      (P<0.01) and 72% lower (P<0.01) at the protein and mRNA level, respectively. In
      cultured rat primary cerebellar astrocytes, hypoxia and inhibition of PKA
      activity significantly reduced glycogen phosphorylase activity and increased
      glycogen accumulation but did not alter glycogen synthase activity. Furthermore,
      elevated glycogen levels provided metabolic support to astrocytes during hypoxia.
      CONCLUSION: Our study has identified that glycogen breakdown is impaired during
      ischemic stroke, the molecular basis of which includes reduced glycogen
      debranching enzyme expression level together with reduced glycogen phosphorylase
      and PKA activity.

PMID- 24858130
TI  - Epigenetics: the neglected key to minimize learning and memory deficits in Down
      syndrome.
AB  - Down syndrome (DS) is the most common genetic intellectual disability, caused by
      the triplication of the human chromosome 21 (HSA21). Although this would
      theoretically lead to a 1.5 fold increase in gene transcription, transcript
      levels of many genes significantly deviate. Surprisingly, the underlying cause of
      this gene expression variation has been largely neglected so far. Epigenetic
      mechanisms, including DNA methylation and post-translational histone
      modifications, regulate gene expression and as such might play a crucial role in
      the development of the cognitive deficits in DS. Various overexpressed HSA21
      proteins affect epigenetic mechanisms and DS individuals are thus likely to
      present epigenetic aberrations. Importantly, epigenetic marks are reversible,
      offering a huge therapeutic potential to alleviate or cure certain genetic
      deficits. Current epigenetic therapies are already used for cancer and epilepsy,
      and might provide novel possibilities for cognition-enhancing treatment in DS as
      well. To that end, this review discusses the still limited knowledge on
      epigenetics in DS and describes the potential of epigenetic therapies to reverse
      dysregulated gene expression. 

PMID- 24858131
TI  - Advanced demodulation technique for the extraction of tissue optical properties
      and structural orientation contrast in the spatial frequency domain.
AB  - We have developed a method for extracting spatial frequency information content
      from biological tissue, which is used to calculate tissue optical properties and
      determine tissue structural orientation. This demodulation method employs a two
      dimensional Hilbert transform using a spiral phase function in Fourier space. The
      approach presented here allows for the determination of tissue optical properties
      using a single frame of data for each modulation frequency, increasing imaging
      speed by two to threefold versus conventional, three-phase spatial frequency
      domain imaging (SFDI). This new single-phase Hilbert transform approach recovers
      optical property and scattering orientation index values within 1% and 10% of
      three-phase SFDI, respectively. These results suggest that, using the Hilbert
      demodulation technique, SFDI data acquisition speed can be increased
      significantly while preserving data quality, which will help us move forward
      toward the implementation of a real-time SFDI platform.

PMID- 24858132
TI  - Detection of circulating tumor cells using targeted surface-enhanced Raman
      scattering nanoparticles and magnetic enrichment.
AB  - While more than 90% of cancer deaths are due to metastases, our ability to detect
      circulating tumor cells (CTCs) is limited by low numbers of these cells in the
      blood and factors confounding specificity of detection. We propose a magnetic
      enrichment and detection technique for detecting CTCs with high specificity. We
      targeted both magnetic and surface-enhanced Raman scattering (SERS) nanoparticles
      to cancer cells. Only cells that are dual-labeled with both kinds of
      nanoparticles demonstrate an increasing SERS signal over time due to magnetic
      trapping.

PMID- 24858133
TI  - Differential protein profile of PC12 cells exposed to proteasomal inhibitor
      lactacystin.
AB  - Parkinson's disease (PD) is the second most common neurodegenerative disease
      worldwide and recent studies implicate a central role for ubiquitin-proteasome
      system (UPS) impairment in the etiopathogenesis of PD. To explore the possible
      role of UPS dysfunction in PD and the proteins involved, PC12 cells were treated
      with 10MUM lactacystin, a 20S proteasome inhibitor, for 24h. Lactacystin induced
      cell death and alpha-synuclein-positive inclusions in cytoplasm. Following two
      dimensional difference in-gel electrophoresis (2-D DIGE) which was used to
      separate the cellular proteins, the proteins that were significantly altered were
      analyzed and identified. Proteomic study identified 6 differentially expressed
      proteins between lactacystin-treated and control cells in this study. Four
      proteins (heat shock 70kDa protein 8, 78kDa glucose-regulated protein, serine
      proteinase inhibitor clade B member 6 and aldehyde reductase) were increased and
      2 proteins (peripherin and tyrosine hydroxylase) were decreased following
      proteasomal inhibition. The results revealed that PC12 cells treated with 10MUM
      lactacystin for 24h could be used as a cellular model of PD. The proteins
      identified in the present indicate not only the damage of proteasomal inhibition
      to the cells but also the possible responses of the cells. These data show that
      proteomic study may provide information relevant to biological basis for PD and
      potential new treatment targets. 

PMID- 24858134
TI  - The relationship between mitochondrial fusion/fission and apoptosis in the
      process of adipose-derived stromal cells differentiation into astrocytes.
AB  - To research the features of mitochondrial fusion and fission proteins and their
      relationship with apoptosis in the process of adipose-derived stromal cells
      (ADSCs) differentiation into astrocytes. Immunocytochemistry and Western-blotting
      were used to analyze the expression of glial fibrillary acidic protein (GFAP),
      mitochondria fusion-2 (Mfn2), mitochondrial fission-1 (Fis1) and cysteine
      aspartate specific protease-3 (Caspase-3). Flow cytometry for quantification of
      the number of apoptotic cells. Transmission electron microscopy (TEM) for
      observation of the ultrastructure. After induced for 48h, 7, 14 and 21 days
      showed expression of GFAP, reached the peak on the 7th day (P<0.05). The
      expression of Mfn2 was decreased with the induction time extending, reached the
      minimum on the 14th day (P<0.05). The expression of Fis1 and Caspase-3 was
      increased with the induction time extending, reached the peak on the 14th day
      (P<0.05, respectively). The rates of early apoptosis, late apoptosis or necrosis
      were increased gradually (P<0.05). Our findings suggest that in the process of
      ADSCs differentiation into astrocytes, mitochondrial fusion decreased while
      mitochondrial fission enhanced significantly; caspase-dependent apoptosis was one
      of the main reasons leading to cell death. 

PMID- 24858135
TI  - Sleep deprivation affects sensorimotor coupling in postural control of young
      adults.
AB  - Although impairments in postural control have been reported due to sleep
      deprivation, the mechanisms underlying such performance decrements still need to
      be uncovered. The purpose of this study was to investigate the effects of sleep
      deprivation on the relationship between visual information and body sway in young
      adults' postural control. Thirty adults who remained awake during one night and
      30 adults who slept normally the night before the experiment participated in this
      study. The moving room paradigm was utilized, manipulating visual information
      through the movement of a room while the floor remained motionless. Subjects
      stood upright inside of a moving room during four 60-s trials. In the first trial
      the room was kept stationary and in the following trials the room moved with a
      frequency of 0.2Hz, peak velocity of 0.6cm/s and 0.9cm peak-to-peak amplitude.
      Body sway and room displacement were measured through infrared markers. Results
      showed larger and faster body sway in sleep deprived subjects with and without
      visual manipulation. The magnitude with which visual stimulus influenced body
      sway and its temporal relationship were unaltered in sleep deprived individuals,
      but they became less coherent and more variable as they had to maintain upright
      stance during trials. These results indicate that after sleep deprivation adults
      become less stable and accurate in relating visual information to motor action,
      and this effect is observed after only a brief period performing postural tasks.
      The low cognitive load employed in this task suggests that attentional
      difficulties are not the only factor leading to sensorimotor coupling impairments
      observed following sleep deprivation. 

PMID- 24858137
TI  - HGF and the regulation of tight junctions in human prostate cancer cells.
AB  - Hepatocyte growth factor (HGF) may impact the metastasis of prostate cancer via
      its action on prostate stem cells or their progeny. Tight junctions (TJs) are
      crucial to the process of metastasis and have been previously shown to be
      regulated by HGF. The present study aimed to evaluate the effect of HGF on the
      function of TJs in human prostate epithelial, prostate stem cell-like and
      prostate cancer cell lines. Four human prostate cancer cell lines (PC-3, DU-145,
      PZHPV-7, CaHPV-10), normal adult prostate parental epithelial cells (RWPE-1) and
      a stem cell-like derivative of RWPE-1 (WPE-STEM) were used to assess HGF-induced
      changes in TJs. A significant difference was noted in the behaviour between the
      WPE-STEM, RWPE-1 and the cancer cell lines which was HGF concentration-dependent.
      However, in the WPE-STEM cells, the effect was biphasic, with the cells seemingly
      resistant to HGF-modulated TJ disruption. Closer examination revealed that HGF
      affected the redistribution of ZO-1, ZO-2 and ZO-3 away from the TJs of confluent
      cells with concurrent loss of claudin-1 and claudin-5, and western blot analysis
      revealed a loss in TJ protein expression of ZO-1 and ZO-2. We demonstrated for
      the first time that HGF regulates TJ function in human prostate cells. Moreover,
      this regulation was dependent on the tumourigenicity of the cells, with the most
      aggressive cells most susceptible and the stem cell-like cells least susceptible.
      These data offer an intriguing glimpse of how TJs affect the behaviour of
      prostate cancer cells and how HGF modulates the expression and function of the
      molecules maintaining TJ structure and function.

PMID- 24858136
TI  - Prevalence of heroin markers in urine for pain management patients.
AB  - Surveys of current trends indicate heroin abuse is associated with nonmedical use
      of pain relievers. Consequently, there is an interest in evaluating the presence
      of heroin-specific markers in chronic pain patients who are prescribed controlled
      substances. A total of 926,084 urine specimens from chronic pain patients were
      tested for heroin/diacetylmorphine (DAM), 6-acetylmorphine (6AM), 6-acetylcodeine
      (6AC), codeine (COD), and morphine (MOR). Heroin and markers were analyzed using
      liquid chromatography tandem mass spectrometry (LC-MS-MS). Opiates were analyzed
      following hydrolysis using LC-MS-MS. The prevalence of heroin use was 0.31%, as
      2871 were positive for one or more heroin-specific markers including DAM, 6AM, or
      6AC (a known contaminant of illicit heroin). Of these, 1884 were additionally
      tested for the following markers of illicit drug use: 3,4
      methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA),
      methamphetamine (MAMP), 11-nor-9-carboxy-Delta(9)-tetracannabinol (THCCOOH), and
      benzoylecgonine (BZE); 654 (34.7%) had positive findings for one or more of these
      analytes. The overall prevalence of heroin markers were as follows: DAM 1203
      (41.9%), 6AM 2570 (89.5%), 6AC 1082 (37.7%). MOR was present in 2194 (76.4%) and
      absent (<LOQ) in 677 (23.6%) of the heroin-positive specimens. COD was present in
      1218 (42.4%) specimens. Prevalence of combinations for specimens containing MOR
      were as follows: DAM only 13 (0.59%), 6AM only 1140 (52.0%), 6AC only 24 (1.1%),
      DAM/6AM/6AC 710 (32.4%), 6AM/6AC 188 (8.6%), DAM/6AM 113 (5.2%), DAM/6AC 6
      (0.27%). Importantly, the prevalence of combinations for specimens without MOR
      were as follows: DAM only 161 (23.8%), 6AM only 217 (32.1%), 6AC only 92 (13.6%),
      DAM/6AM/6AC 50 (7.4%), 6AM/6AC 7 (1.0%), DAM/6AM 145 (21.4%), DAM/6AC 5 (0.74%).
      Unexpected patterns of excretion were observed, such as the presence of DAM and
      6AC in the absence of 6AM and MOR; therefore, multiple heroin markers may be
      useful to assess for heroin use. 

PMID- 24858140
TI  - Nine new farnesylphenols from the basidiomycete albatrellus caeruleoporus.
AB  - Nine previously-unreported farnesylphenols, involving eight neogrifolin
      derivatives (1-8) and one grifolin analogue (9), together with three known
      compounds, were isolated from the fruiting bodies of the mushroom Albatrellus
      caeruleoporus. Their structures were elucidated as (S)-17-hydroxy-18,20-ene
      neogrifolin (1), (S)-18,19-dihydroxyneogrifolin (2), (S)-9-hydroxy-10,22-ene
      neogrifolin (3), (9S,10R)-6,10-epoxy-9-hydroxyneo grifolin (4), (9S,10R)-6,9
      epoxy-10-hydroxyneogrifolin (5), (-)-13,14-dihydroxyneogrifolin (6), albatrelin G
      (7), albatrelin H (8), and one grifolin analogue, (S)-10-hydroxygrifolin (9),
      grifolin (10), neogrifolin (11), and albatrellin (12) by extensive spectroscopic
      analyses and chemical methods. Compounds 7 and 8 showed weak cytotoxic activity
      to cell lines HL-60, SMMC-7721, A-549, and MCF-7, in vitro. 

PMID- 24858141
TI  - Vitamin D supplementation of breastfed infants: a randomized dose-response trial.
AB  - BACKGROUND: Breastfed infants require supplementation with vitamin D (vD), but
      little is known about the necessary dose. This double blind trial evaluated four
      different doses of vD. METHODS: Exclusively breastfed infants (N = 213) were
      randomized at 1 mo to one of four doses, which they received through 9 mo while
      receiving no formula. The supplements provided daily 200 IU, 400 IU, 600 IU, or
      800 IU of vD. The primary endpoint was plasma 25(OH)D level, and secondary
      outcomes were plasma parathyroid hormone and calcium, and illness incidence. The
      study was conducted during winter at 41 degrees  N. RESULTS: Most infants had low
      (<50 nmol/l) 25(OH)D levels at 1 mo, but with supplementation levels rose.
      Overall, levels of 25(OH)D differed significantly in proportion to vD dose. There
      were no effects of vD on illness incidence or growth. Low levels were common,
      with 7.8% of levels being <50 nmol/l and 15 infants having 2 to 4 low levels.
      CONCLUSION: The four doses of vD produced different plasma levels of 25(OH)D. The
      higher doses were somewhat more efficacious in maintaining vD sufficiency in
      breastfed infants. The findings support the recommended dose of 400 IU/d, and
      stress the need to start supplementation at birth.

PMID- 24858142
TI  - Maternal surfactant protein A influences the immunoprotective properties of milk
      in a murine model.
AB  - BACKGROUND: Maternal surfactant protein A (SP-A), a collectin with innate immune
      system function, is critical to newborn mouse survival preventing bacterial
      peritonitis associated with a nonhygienic environmental exposure. We hypothesized
      that SP-A improves newborn survival by optimizing milk immunoprotection. METHODS:
      Regional (lung) and systemic (milk and serum) immunologic responses to a novel
      antigen, 2,4-dintirophenyl keyhole limpet hemocyanin (DNP-KLH), and to a
      nonhygienic environment were evaluated in wild-type (WT) and SP-A null murine
      dams. Cross-fostering pups assessed the impact of milk on newborn survival.
      RESULTS: Maternal SP-A optimized antigen-specific milk secretory IgA (sIgA)
      production following the DNP-KLH exposure. Milk total and environment-specific
      sIgA production was not dependent on maternal SP-A in the nonhygienic exposure.
      At baseline, SP-A null milk contained physiologically meaningful increases in two
      proinflammatory cytokines compared with WT milk. The lack of SP-A plus the
      nonhygienic environmental exposure synergistically increased the number of
      proinflammatory cytokines contained in milk. Finally, the SP-A null genotype
      decreased pup survival during a nonhygienic environmental exposure. CONCLUSION:
      Maternal SP-A impacts milk sIgA and cytokine content, and is associated with
      improved newborn health.

PMID- 24858143
TI  - Bangladeshi leadership in Diabetology: insights from DAWN 2 study.

PMID- 24858144
TI  - Culture of pathogenic campylobacter species at Mymensingh Medical College.
AB  - Childhood diarrhea represents a major public health problem in developing
      countries, where campylobacteriosis is widespread and causes significant
      morbidity and mortality in infants and children. Despite the increasing
      importance of campylobacteriosis, most developing countries and even many
      developed countries do not have surveillance systems to measure the health and
      economic burden of human campylobacteriosis, nor detect trends in outbreaks. The
      present study was carried out to diagnose etiology of diarrhea caused by
      Campylobacter species. A total of 150 clinically diagnosed diarrheal pediatric
      patients were included in this study, of which 98(65.3%) were male and 52(34.6%)
      female from the Department of Pediatrics, Mymensingh Medical College Hospital,
      Mymensingh, Bangladesh from July 2011 to April 2012. Stool specimens were
      collected from each of the cases. The specimens were cultured in appropriate
      media and Campylobacters were isolated and identified by recommended tests. Among
      150 cases, 17(11.3%) were culture positive for Campylobacter species, of which
      15(88.2%) were C. jejuni and 02(11.7%) were C. coli. Of the cases, below 1 year
      of age group were 106(70.6%) cases showing 12(70.5%) positive for Campylobacters
      and 44(29.33%) cases were above 1 year of age group showing 05(29.41%) positive.
      The prevalence of Campylobacter infection found in the present study was higher
      below 1 year age group and was very much close to other countries of this
      subcontinent. 

PMID- 24858145
TI  - Comparison of creatinine clearance estimates with routine measured creatinine
      clearance in hospitalized chronic kidney disease patients.
AB  - The aim of this study was to determine the correlation between endogenous
      creatinine clearance (BSA adjusted), the Modification of Diet in Renal Disease
      (MDRD) and Cockcroft-Gault (BSA adjusted) equations in a Bangladeshi population
      with chronic kidney disease. It was an observational study conducted from July
      2011 to January 2012 in the department of Medicine of Mymensingh Medical College
      Hospital, Mymensingh, Bangladesh. A total of 50 cases with diagnosed Chronic
      kidney disease (CKD) patients participated in this study. Results are expressed
      as mean and standard deviation (SD). Pearson correlation coefficient (r) was used
      to compare the results of conventional creatinine clearance on 24 hour urine
      collection (BSA adjusted) and creatinine clearance calculated by Cockcroft-Gault
      creatinine clearance (BSA adjusted) and MDRD creatinine clearance (ml/min/1.73m2)
      equation. Among 50 patients 30(60%) were male and 20(40%) were female. Mean age
      of the cases was 43+/-12.96 years with age range from 18 to 65 years. Mean
      creatinine clearance measured on 24 hours urine collection (BSA adjusted) was
      13.86+/-8.72ml/min per 1.73m2. Mean BSA adjusted Cockcroft-Gault creatinine
      clearance and MDRD creatinine clearance were 27.68+/-11.26 and 24.46+/
      11.05ml/min per 1.73m2 respectively. There was a positive correlation between
      both the Modification of Diet in Renal Disease (r=0.951, p<0.05) equation and the
      Cockcroft-Gault (r=0.948, p<0.05) equation with measured creatinine clearance;
      the former being statistically superior comparing the correlation coefficients.
      The creatinine based formulas with their inherent property of convenience and
      cost effectiveness can be a useful tool for monitoring the progression of
      disease. 

PMID- 24858146
TI  - Fasting serum glucose and glycosylated hemoglobin level in obesity.
AB  - Obesity is a condition in which the body fat stores are increased to an extent
      which impairs health and leads to serious health consequences. The amount of body
      fat is difficult to measure directly, and is usually determined from an indirect
      measure - the body mass index (BMI). Increased BMI in obese persons is directly
      associated with an increase in metabolic disease, such as type 2 diabetes
      mellitus. This Analytical cross sectional study was undertaken to assess the
      relation between obesity and glycemic control of body by measuring fasting serum
      glucose and glycosylated hemoglobin. This study was carried out in the Department
      of Physiology, Mymensingh Medical College, Mymensingh from 1st July 2011 to 30th
      June 2012 on 120 equally divided male and female persons within the age range of
      25 to 55 years. Age more than 55 years and less than 25 years and diagnosed case
      of Hypothyroidism, Cushing's syndrome, polycystic ovary, Antipsychotic drug user
      and regular steroid users were excluded. Non probability purposive type of
      sampling technique was used for selecting the study subjects. Measurement of body
      mass index was done as per procedure. Fasting serum glucose was estimated by
      glucose oxidase method and Glycosylated hemoglobin by Boronate Affinity method.
      Statistical analysis was done by SPSS (version 17.0). Data were expressed as
      Mean+/-SE and statistical significance of difference among the groups were
      calculated by unpaired student's 't' test and Pearson's correlation coefficient
      tests were done as applicable. The Mean+/-SE of fasting serum glucose was
      significant at 1% level (P value <0.001) for obese group of BMI. There was no
      significant difference of glycosylated hemoglobin level between control and study
      groups. But there was positive correlation within each group. Fasting serum
      glucose also showed a bit stronger positive correlation with BMI. Both obese male
      and female persons showed higher levels of fasting serum glucose and glycosylated
      hemoglobin. The observed positive correlation between BMI with fasting serum
      glucose and glycosylated hemoglobin emphasizes the importance of maintenance of
      normal BMI to prevent early onset of type 2 diabetes mellitus. 

PMID- 24858147
TI  - Complications of endonasal endoscopic sinus surgery for management of nasal polyp
      and chronic sinusitis.
AB  - Sinusitis is defined as a condition manifested by inflammation of the mucous
      membrane of the nose & paranasal sinuses, fluid within this cavities and or
      underlying bone. Chronic rhinosinusitis is diagnosed by the presence of two or
      more of the following factors facial congestion/fullness, nasal obstruction,
      nasal discharge or discolored post nasal drainage, hyposmia/anosmia or one major
      and two of the following minor factors, headache. Halitosis, fatigue, dental
      pain, cough, ear pressure, fullness. The use of endoscope during surgery of nose
      & para nasal sinuses improves visualization enable greater preservation of normal
      structures and reduces the necessity for wide exposure. This cross-sectional
      study on 50 cases of chronic rhinosinusitis carried out during a period of 6
      months. All the cases of both endonasal endoscopic sinus surgery (EESS) group and
      conventional group assessed clinically endoscopicaly and by imaging both pre and
      post-operative period. Twenty five cases were EESS group. Twenty five cases of
      conventional group. Follow-up frequencies are 1st week, 2nd week, 3rd week, 1st
      month, 3rd months, 6th months. In both type majority of patients in between 21-40
      years, most of the cases were male, majority of patients present with headache
      (80)%, nasal discharge (70%), nasal obstruction (62%), major indication incase of
      EESS group were ethmoidal polyp 52% & conventional surgery group were chronic
      sinusitis (56%). Commonest complications were cheek swelling 10(40%) incase of
      conventional group, crusting 12(84%) in EESS group. Complete recovery incase of
      EESS were in 21(84%) cases and conventional surgery group 16(64%). Endonasal
      endoscopic sinus surgery has provided a safe & efficient method for dealing with
      different sinonasal diseases. 

PMID- 24858148
TI  - Prevalence of HBV and HCV among the multi-transfused beta thalassemic major
      patients in a day care centre of blood transfusion department of Mymensingh
      Medical College Hospital.
AB  - Though regular blood transfusion improves the overall survival of patients with
      beta-thalassemia which is one of the most common genetic diseases in the world,
      carries a definite risk of infection with blood-borne viruses. It is a major
      health problem, brings much morbidity, early mortality and a great deal of misery
      for a family both financially and emotionally. World Health Organization (WHO)
      reported that there is about 3% beta thalassemia carrier and more than two
      thousand thalassemic children are born every year in Bangladesh. We carried out
      this study to provide epidemiologic data on hepatitis B virus (HBV) & hepatitis C
      virus (HCV) infection among beta-thalassemic patients. Moreover, HBV & HCV
      infection-associated risk factors were investigated in this study. Two hundred
      patients with beta-thalassemia major were enrolled in this study. Using Rapid
      Immuno-chromatographic Test and their sera were tested for HBsAg and HCVAb. The
      positive HBsAg & HCVAb results were confirmed by ELISA. The study sample 200
      consisted of 165 males (82.5%) and 35 females (17.5%), with a mean+/-SD age of
      5.9+/-9.0 years. Four (2%) patients were HCV-Ab positive; 13(6.5%) were HBsAg
      positive. Univariate analysis showed that (P=0.01), older age (P=0.001), longer
      transfusion duration (P=0.000), HBsAg seropositivity (P=0.03), and higher serum
      ferritin level (P=0.002) were significantly associated with a higher prevalence
      of HCV. Using multivariate analysis, age (P<0.001), serum ferritin level (P<
      0.001) were independent factors associated with HCV infection. Improvement of the
      people's knowledge about TTI risk factors, blood screening strategies and HBV
      vaccination have led to a dramatically decrease in prevalence of TTIs
      particularly HBV during the last decades in Bangladesh.However, post-transfusion
      transmission of HCV has still remained a major health concern in multi-transfused
      patients. As the prevalence of HCV infection is much higher among beta
      thalassemic patients as compared with HBV infections routine screening of donated
      blood for HCV is highly recommended by ELISA. 

PMID- 24858149
TI  - Comparison of efficacy of labetalol and fentanyl for attenuating reflex responses
      to laryngoscopy and intubation.
AB  - Stress response due to laryngoscopy and intubation has been universally
      recognized phenomenon resulting in increase in heart rate, arterial,
      intracranial, and intraocular pressure. Various pharmacological approaches have
      been used to blunt or attenuate such pressure responses. This prospective,
      randomized, placebo controlled, double blinded study was designed to compare the
      efficacy of bolus dose of Labetalol and Fentanyl for attenuating reflex responses
      to laryngoscopy and intubation. Ninety patients with physical status of ASA I and
      II were scheduled for elective surgery under standard protocol of general
      anaesthesia, randomly allocated into three groups, consisting of 30 patients in
      each group, assigned as C (Control), L (Labetalol), and F (Fentanyl). In control
      group 10ml of 0.9% saline, in Labetalol group 0.25 mg/kg Labetalol and in
      Fentanyl group 2MUgm/kg of Fentanyl were given intravenously at 3 minutes prior
      to laryngoscopy and intubation. Pulse rate, systolic, diastolic, mean arterial
      pressure and rate pressure products (RPP) were recorded before and after
      premedication, after administration of study drugs and at 1, 3, 5, 10 and 15
      minutes after intubation. For statistical analysis of data, ANOVA tests were
      performed for comparison between groups. There were an increase in heart rate,
      systolic, diastolic, mean arterial pressures and rate pressure product in all the
      three groups after intubation in comparison to base line value. But the rise was
      minimum in L and F group as compared to C group which is statistically
      significant and also minimum in L group as compared to F group. So Labetalol is
      better agent for attenuation of laryngoscopic and intubation reflex. 

PMID- 24858150
TI  - Delayed primary suture prevents wound infection in patients with obstructive
      jaundice and septic abdomen.
AB  - This study was undertaken to assess the efficacy of delayed primary closure in
      prevention of postoperative wound infection in patients with obstructive jaundice
      and septic abdomen. Here analyzed 93 patients retrospectively who underwent
      surgery in hepato-biliary-pancreatic unit of Bangabandhu Sheikh Mujib Medical
      University, Dhaka, Bangladesh from January 2011 to June 2011. Primary closure of
      the abdominal wound was applied in all patients. There was no mortality, but 21
      patients had postoperative morbidity (wound infection in 17, intra-abdominal
      abscess in 1, melaena in 1, biliary leakage in 1, burst abdomen in 1). Seventy
      two patients had uneventful postoperative recovery were included in Group 1.
      Patients who developed postoperative wound infection (n=17) were included in
      Group 2. Rest 4 patients who developed other complications were excluded from the
      study. Pre-, per and postoperative parameters were compared between two groups
      for identifying the risk factors for SSI. Delayed primary closure of the wound
      was applied prospectively in 21 patients (Group 3) on the basis of retrospective
      results and the outcome was assessed. Retrospective analysis revealed that the
      patient who developed wound infections (Group 2) after primary closure;
      significantly greater number of patients had obstructive jaundice or intra
      abdominal septic condition preoperatively. Prospective results revealed that
      there was no wound infection in 21 patients with in obstructive jaundice or intra
      abdominal sepsis in which delayed primary closure was applied. Hospital stay was
      significantly reduced in Group 3 in compare to Group 2. In subsequent follow up,
      it has been found that 2 patients developed incisional hernia in Group 2 patients
      but none in Group 3 patients. Delayed primary closure of the wound is a good
      option in patient with obstructive jaundice and intra-abdominal septic condition
      for preventing postoperative wound infection. 

PMID- 24858151
TI  - Incidence of post obturation pain following single and multi visit root canal
      treatment in a teaching hospital of Bangladesh.
AB  - Post obturation pain is the pain of any degree after endodontic treatment. There
      are different opinions regarding incidence of post obturation pain related to
      single and multi visit root canal treatment. This prospective study was conducted
      to evaluate the incidence of post obturation pain in single visit and multi visit
      root canal treatment and to compare the incidence of pain between the two
      treatment groups. A total of 120 cases of endodontically involved asymptomatic
      non vital single rooted teeth were selected for this study. The patients were
      assigned and divided in to two treatment groups, sixty patients each. In single
      visit group, all teeth were prepared and filled using the standardized
      preparation and lateral condensation filling technique. In the multi visit
      treatment group, at the first appointment, the teeth were prepared, and dressed
      with calcium hydroxide paste for 7 days. At the second appointment, the teeth
      were prepared and obturated by using lateral condensation technique. The
      frequency of post obturation pain was recorded as no pain, slight, moderate and
      severe pain and evaluated at the day 1 and at the day 7 after obturation. The
      data were analyzed statistically by using SPSS version-12. P value <0.05 was
      taken as significant. The study showed that the post obturation pain in the
      single visit treatment group was more than multi visit treatment group, which is
      significant (p value <0.044). Out of the 120 patients, 86(71.7%) patients had no
      pain, 19(15.8%) had slight pain and 15(12.5%) patients had moderate pain at the
      day 1 after obturation. At the day 7 after obturation, 108(90%) patients had no
      pain, 9(7.5%) had slight pain and 3(2.5%) patients had moderate pain. No patient
      noticed severe pain during the follow up period. Older patient had significantly
      more post obturation pain than the younger patient. There was higher incidence of
      post obturation pain following the single visit root canal treatment. In multi
      visit root canal treatment with intra-canal medicaments seems to reduce the post
      obturation pain. 

PMID- 24858152
TI  - Long versus standard initial prednisolone therapy in children with idiopathic
      nephrotic syndrome.
AB  - The efficacy of longer initial course of prednisolone with standard regimen was
      compared in children with idiopathic nephrotic syndrome (INS). It was a
      randomized controlled trial in which patients with INS who responded to initial
      course of prednisolone, either long or standard regimen were included and
      followed for one year after completion of treatment of first attack. The long
      regimen consisted of prednisolone 60mg/m2/day for six weeks followed by 40mg/m2
      every alternate day single morning dose for further six weeks. The standard
      regimen consisted of prednisolone 60mg/m2/day for four weeks followed by 40mg/m2
      every alternate day single morning dose for further four weeks. There were 93
      children who fulfilled the criteria of the study, 47 from long group and 46 from
      standard group though ultimately 72 completed the study (41 from long and 31 from
      standard group). The primary outcome measure was relapse within next one year.
      Relapse within one year was noted in 73.2% of long and 64.5% of standard group.
      The odds ratio for relapse within one year was 0.80 (95% confidence interval
      0.22, 2.05). This did not reach statistical significance (p=0.696). Adverse
      effects of prednisolone between two groups were also not statistically
      significant (p>0.05). Prolongation of prednisolone therapy for initial episode of
      steroid-sensitive INS does not have a beneficial effect on the outcome in next
      one year. 

PMID- 24858153
TI  - Evaluation of ophthalmic manifestations in patients with intracranial tumours.
AB  - The present study was done to observe the ophthalmic manifestations in patients
      with intracranial tumor. This was a prospective, purposive, consecutive,
      observational study conducted in patients with radiologically proven intracranial
      tumors in the department of Ophthalmology with collaboration of Department of
      Neuro-surgery of Bangabandhu Sheikh Mujib Medical University from January 2006 to
      December 2010. All cases had tissue histopathology confirmation post-operatively.
      The most common type of intracranial tumor was pituitary adenoma (58.04%),
      followed by craniopharyngioma (20.53%), posterior fossa tumour (12.50%)
      [medulloblestoma, ependymoma], meningioma (8.04%) [sphenoidalwing meningioma,
      petroclavel meningioma, oligodendroglioma] and others (0.89%) [nasopharyngial
      carcinoma, esthesio - astrocytoma]. Common neuro-ophthalmological findings were
      visual blur (91.07%), visual field defect (71.42%), optic disc changes (50%),
      pupillary light reaction defect (48.21%) and colour vision defect (46.42%). The
      study shows, pituitary adenoma is the most common tumor that impairs the visual
      pathway structures followed by craniopharyngioma, posterior fossa tumour &
      meningioma. Furthermore, decreased visual acuity, visual field defect, abnormal
      optic discs, relative afferent pupillary defect and ophthalmoplegia etc. are the
      common neuro-ophthalmic features that should be carefully examined for early
      detection of intracranial tumors. 

PMID- 24858154
TI  - The spectrum of pathological changes in breast cancer following neoadjuvant
      chemotherapy.
AB  - Breast cancer with advanced stage is common in Bangladeshi women. For the
      treatment of this deadly disease neoadjuvant chemotherapy (NAT) is the recent
      standard of care. NAT is useful for down-staging and to prevent micro-metastasis
      of tumour, on the other hand it causes variable clinical and pathological
      responses. This observational study was aimed to evaluate the morphological
      changes in neoplastic, nonneoplastic breast tissue and in the lymph nodes after
      NAT. To identify the clinical response and post operative histologic changes,
      this study prospectively selected 35 patients with locally advanced breast cancer
      treated with NAT. In these patients clinical response was assessed based on
      tumour size. Mastectomy specimens were collected and samplings were done in
      specific method. Majority (68%) of patients presented with breast lump measuring
      over 5cm with enlarged lymph nodes. After NAT the lump size reduced to <5cm and
      lymph nodes became nonpalpable in most (60%) of the patient. Complete clinical
      response (cCR) was observed in five patients. For histopathological evaluation,
      the tumour cellularity was semi quantitatively measured. Seventeen percent (17%)
      patient presented with 50% tumour cellularity in tumour bed. Most striking
      cytologic atypia was nuclear changes. The characteristic patterns of stomal
      changes were observed. Only 8 patients showed nonneoplastic breast tissue
      changes. In lymph nodes hyaline stromal scar was most commonly (23%) seen. This
      study observed that 2 patients had pathological complete response out of 5
      clinically complete response patients. This study concluded that the knowledge of
      morphologic spectrum of treatment-induced breast tissue change is important for
      the pathologist to avoid misdiagnosis. This will help the clinician to take
      rational decision for management of the locally advanced breast cancer. 

PMID- 24858155
TI  - Clinical and haemato-pathological characteristics of adult acute lymphoblastic
      leukaemia.
AB  - Acute lymphoblastic leukaemia (ALL) is a heterogeneous group of disorders. It
      varies with respect to the morphologic, cytogenetic, molecular and immunologic
      features of the neoplastic cells reflecting the variable clinical-pathologic
      presentations and outcome of the patients. The aim of the study was to observe
      the clinical and haemato-pathological characteristics in newly diagnosed adult
      ALL patients. A total number of 61 patients morphologically diagnosed as acute
      lymphoblastic leukaemia aged 15 and above assigned for this observational study.
      The study was carried out in the Department of Haematology, BSMMU from January
      2007 to December 2008. Among 61 patients, aged 15 to 80 years with median age 25
      years, 79% were male and 21% were female. Most of the patients presented with
      anaemia (67%), fever (66%), lymphadenopathy (64%) and splenomegaly (57%). Other
      common clinical findings were hepatomegaly (39%), bone tenderness (44%) and
      bleeding manifestations (34%). Among haemato-pathological findings 67% patients
      had Hb level <=10gm/dl, 46% patients had WBC count >=30*109/L, 67% patients had
      platelet count <=100*109/L, 93% patients had blast in peripheral blood and 61%
      patients had >=90 % blasts in the bone marrow at the time of diagnosis. In this
      study adult ALL patients were analyzed only for their clinical and haemato
      pathological characteristics. But their biologic characteristics were not
      analyzed due to lack of availability of facility. A progressive understanding of
      the biologic and genetic characteristics of ALL will allow us to identify
      different prognostic subgroups with specific molecular and cellular features. All
      the necessary measures have to be developed in our country in order to identify
      prognostically distinct subgroups of patients. 

PMID- 24858156
TI  - Role of protocol biopsy in early graft dysfunction in renal transplant recipient.
AB  - This study was designed to evaluate the role of protocol biopsy in renal
      allograft recipients. A total of thirty five kidney transplant recipients with a
      mean age of 35+/-5 years included in this study. Mean age of donor was 41+/-8
      years. The study was performed from April 2008 to November 2009 in the Department
      of Nephrology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka,
      Bangladesh. Immunosuppressive protocol used for transplant patient was,
      Cyclosporine 8mg/kg/day, Mycophenolate mofetil (MMF) 500mg twice daily,
      Prednisolone 0.5mg/kg/day. Protocol biopsy done on day 0 (Peroperative), day 14
      and day 90. Stains used H&E and PAS. Cyclosporine blood level was done on 7th and
      14th postoperative day and monthly for 3 months. Serum creatinine was done daily
      for 14 days & then weekly upto 3 months. Among 35 patients 23(66%) showed normal
      graft function and 12(34%) early graft dysfunction. Aetiology of early graft
      dysfunction includes 50% clinical rejection, 17% acute tubular necrosis (ATN),
      17% cyclosporine toxicity, 8% graft thrombosis and 8% recurrence of GN. Per
      operative protocol biopsy showed normal histology in 28(80%) cases, in 4 cases
      11% glomeruli showed sclerosis and in 3 cases 9% glomeruli showed sclerosis. At
      14th post operative day 60% patients showed normal histology, 14% had clinical
      rejection (elevated serum creatinine along with histological features of
      rejection), another 14% had sub clinical rejections (normal serum creatinine with
      histological changes), cyclosporine toxicity 5.6%, ATN 5.6%, and recurrent
      glomerulonephritis in 3% cases. Among clinical rejection, according to Banff
      numerical classification, Grade-1 (20%), Grade-2 (60%), Grade-3 (20%) and among
      sub clinical rejections Banff Grade-1 (80%), Grade-2 (20%). Biopsy after 3 months
      showed normal histology 54.28%, clinical rejection 11.42%, sub clinical rejection
      5.7%, borderline change 5.7%, cyclosporine toxicity 5.7% & 2.8% recurrent
      glomerulonephritis. According to Banff numerical classification in clinical
      rejection Banff Grade-1 (25%), Grade-2 (50%) and Grade-3 (25%). Among subclinical
      rejection Banff Grade-1 (70%), Grade-2 (30%). 

PMID- 24858157
TI  - Maternal and fetal outcome of mothers with gestational diabetes mellitus
      attending BIRDEM Hospital.
AB  - Gestational diabetes mellitus, most of which progress to type-2 diabetes mellitus
      is increasing worldwide. Identification of gestational diabetes and control of
      glucose can reduce such complications and improve maternal and neonatal health. A
      hospital based cross sectional study was conducted to find out maternal and fetal
      outcome of gestational diabetes from January to July 2011. Data were collected
      from 109 gestational diabetes mothers attending Bangladesh Institute of Research
      and Rehabilitation in Diabetes, Endocrine and Metabolic Disorders (BIRDEM)
      hospital for delivery. Study revealed that gestational diabetes was more common
      among mothers aged >25 years old and multiparaous women. Mean gestational age of
      diagnosis was 16.82+/-9.54 weeks. Sixty eight (68%) mothers were diagnosed before
      20 weeks of gestation and more than 90% mothers with gestational diabetes
      delivered by caesarean section. Mean pregnancy weight gain was 6.8+/-1.18kg.
      Adverse maternal outcome observed in 24% cases and adverse fetal outcome was
      present in 34% cases. In univariate analysis weeks of delivery and fasting blood
      sugar were statistically significantly associated with adverse pregnancy outcome.
      Babies born to mothers with only diet restriction had less birth weight than
      mothers with insulin therapy. Pregnancy thought to be the most vulnerable stage
      of women's life and protecting her health along with her fetus during this period
      yields a positive impact on the health of future generation. Particular attention
      should be given during antenatal period to initiate screening programme and
      treatment protocol for gestational diabetic mothers. 

PMID- 24858158
TI  - Use of local anesthesia in transrectal ultrasound guided prostatic biopsy.
AB  - Transrectal ultrasound (TRUS) guided biopsy of the prostate is the gold standard
      for detecting prostate cancer. Intraprostatic administration of local anesthesia
      significantly decreases pain during prostatic biopsy. Transrectal ultrasound
      guided intraprostatic lidocaine administration along with intrarectally lidocaine
      gel is a new local anesthesia technique for prostatic biopsy. It was a randomized
      prospective, comparative, interventional type of the study. A total of 60
      patients of age over 55 years included in the study among them 30 patients with
      transrectal lidocaine gel was in Group I and 30 patients with intraprostatic
      lidocaine injection with intra rectal gel were in Group II. The mean age was
      almost identically distributed between the two groups (p=0.668). About 47% of
      patients in Group I exhibited hard prostate on digital rectal examination (DRE),
      33.3% single nodule and 20% multinodule compared to 33.3% of patients in Group II
      had hard prostate, 26.7% single nodule and 40% multinodule (p=0.236). The mean
      serum prostate specific antigen (PSA) was significantly higher in Group II than
      that in Group I (36.7+/-9.2 vs. 7.5+/-5.8ng/ml; p=0.007). The mean pain intensity
      during biopsy was almost two times higher in Group I than in Group II (p<0.001).
      The present study concludes that the intraprostatic lidocaine injection along
      with intra rectal lidocaine gel is less painful method and can be considered in
      all patients undergoing transrectal ultrasound guided prostate biopsy. 

PMID- 24858159
TI  - Comparison between arthroscopic partial and total meniscectomy of medial meniscus
      in non-professional athletes.
AB  - Large number of patients suffers from medial meniscus injury during athletic
      activities despite of not being involved in professional sports. Our goal was to
      compare clinical and functional outcome of arthroscopic partial meniscectomy with
      results of arthroscopic total meniscectomy of the medial meniscus in these non
      professional athletes. The prospective interventional study was carried out in a
      five years period from January 2007 to December 2011. According to predefined
      inclusion and exclusion criteria 109 patients were selected and underwent surgery
      but 29 patients lost from follow-up. Results of 40 cases with Arthroscopic
      partial meniscectomy (Group-I) and 40 cases with arthroscopic total meniscectomy
      (Group-II) were analyzed. There were 75 male patients and the predominant age
      group was 21-30 years. Patients were followed up for a range of 36-60 months.
      Standard questionnaires of Visual Analogue Score (VAS), Knee injury and
      Osteoarthritis Outcome Score (KOOS), Tegner-Lysholm Knee Score (TLKS) and Tapper
      and Hoover criteria was used to assess and compare the outcomes. Radiological
      assessment was done to note any changes. Students were sufferers in majority
      cases and bucket handle tear had been the commonest type. Significant difference
      of clinical, functional and radiological outcome was observed at minimum 3 years
      follow up. One case needed revision in Group-II and the infection rates were
      insignificant. Arthroscopic partial meniscectomy is significantly better method
      for surgical management of medial meniscus injuries. 

PMID- 24858160
TI  - Diameter of the lymphoid follicles in the vermiform appendix of Bangladeshi
      cadaver.
AB  - Appendicitis is the most common clinical condition of the appendix. Many cases of
      acute appendicitis result from obstruction of the lumen of the appendix by
      lymphoid hyperplasia. The vermiform appendix is a worm-like, closed-ended,
      narrow, small tubular structure, projecting from posteromedial wall of cecum. It
      is an integral part of the Gut Associated Lymphoid Tissue (GALT) system. The
      lymphoid follicles of the vermiform appendix vary in respect to their number,
      diameter and location in different ages. This study was done to measure and
      establish the normal diameter with age related variation of the lymphoid
      follicles of vermiform appendix in Bangladeshi population. This descriptive cross
      sectional study was carried out in the Department of Anatomy, Sir Salimullah
      Medical College, Dhaka, from January 2008 to June 2009. Sixty (60) postmortem
      vermiform appendices of different age groups of Bangladeshi cadavers. For
      studying the diameter of lymphoid follicles in the vermiform appendix in relation
      to age, the collected samples were divided into five groups namely Group-A
      between age ranges 0-20 years, Group-B between age ranges 21-30 years, Group-C
      between age ranges 31-40 years, Group-D 41-50 years and Group-E age above 50
      years. From each age group, six (6) fresh samples were selected for histological
      study. From each vermiform appendix three slides were prepared each from its
      base, middle part and near the tip and were stained with routine H & E stain. The
      normal diameter of the follicles of the vermiform appendix ranged from 0.40 mm to
      0.66 mm. The highest average group diameter was 0.62+/-1.10mm in Group-A and the
      lowest value was 0.45+/-2.73mm in Group-E. It was obvious that the diameter
      decreased gradually with advancing age. The average normal diameter of the
      lymphoid follicles per histological section of vermiform appendix reduced with
      advancing age and showed a significant negative correlation with age (p<0.001).
      In the present study, the normal diameter of the lymphoid follicles of the
      vermiform appendix reduced significantly with advancing age. 

PMID- 24858161
TI  - Endodontic management of symptomatic pulpal pathosis by single -visit root canal
      therapy.
AB  - Single-visit root canal therapy is one of the reality in modern endodontics
      globally, both for vital and non-vital teeth, despite many research efforts and
      much controversy, specially when post-operative pain is concerned. There are
      increased post-operative complications as pain, swelling, discomfort in managing
      teeth having symptomatic pulpal pathosis. To clinically verify the possibility to
      treat symptomatic vital and non-vital teeth in one visit technique, 126 patiens
      were selected and advised to undergone single visit endodontic treatment at the
      Department of Conservative Dentistry and Endodontics, Bangabandhu Sheikh Mujib
      Medical University, Dhaka. Endodontically involved symptomatic vital and
      symptomatic non-vital teeth were enrolled in two groups and advised to undergone
      single visit endodontic treatment. Both groups were assessed at 24 hours, 48
      hours, 72 hours and long term post operative evaluation up to 10 months. The main
      outcome measure was post operative pain. The result of our study indicates that
      single visit root canal treatment is a safe, effective and practical method of
      treatment of an endodontically involved tooth both in vital and non vital cases
      when applied in appropriate situation. Significantly fewer patients of
      symptomatic vital cases reported pain in immediate follow up i.e. 24 hours, 48
      hours and 72 hours in comparison to non vital cases (12.69% vs. 22.2%, 4.16% vs.
      11.11%, 1.58% vs. 7.93%). At 10 months of long term follow up the recall rate was
      74.35% and 90(71%) of patients were comfortable after receiving treatment. Post
      operative pain incidence in single visit was equivalent to that of multi visit
      endodontics, provided one had an accurate diagnosis, proper case selection and
      skilled technique. 

PMID- 24858162
TI  - Cardiovascular complications in patients with end stage renal disease on
      maintenance haemodialysis.
AB  - This cross-sectional study was carried out at Bangabandhu Sheikh Mujib Medical
      University (BSMMU), Dhaka Medical College Hospital (DMCH), National Institute of
      Kidney Diseases & Urology (NIKDU) and Kidney Foundation from July 2005 to June
      2007 to find the cardiovascular complications in end stage renal disease (ESRD)
      patients on maintenance haemodialysis. Patients of both sexes with age ranging
      from 18-59 years and getting at least 8 hours of haemodialysis per week for the
      last 3 months were enrolled in the study. A total of 126 such patients were
      included in the study. Among 126 patients 77(61.1%) developed some types of
      cardiovascular complications. In terms of type of complications 63.6% of the
      patients had LVH, 23.4% had ischemic heart disease (IHD) and 10.4% had congestive
      heart failure (CCF) and 2.6% cardiomyopathy. Over 96% patients were hypertensive,
      followed by 46.8% diabetics and 42.1% smokers. Presence of hypertension,
      diabetes, family history of diabetes and hypertension were observed to be
      significantly higher in patients who developed cardiovascular complications
      (p<0.05). It is deserved that cardiovascular complications (CVC) are very common
      in ESRD patients on maintenance haemodialysis (MHD). Poor control of blood
      pressure, low Haemoglobin level and poor glycaemic control are higher in ESRD
      patients on MHD and are possibly related to the development of cardiovascular
      complications. 

PMID- 24858163
TI  - Peginterferon alpha-2a and rivabirin in the treatment of chronic hepatitis C.
AB  - Peginterferon alpha-2a with ribavirin produces significantly higher sustained
      virological response (SVR) in comparison to conventional interferon monotherapy
      in patients with chronic hepatitis C virus (HCV) infection. We evaluated the
      efficacy and safety of peginterferon alpha-2a plus ribavirin combination in the
      treatment of chronic hepatitis C among Bangladeshi patients. A total of 64
      patients were randomly selected in this study and were assigned for treatment
      with peginterferon alpha-2a 180MUg once weekly plus ribavirin daily for 24 weeks
      in case of genotypes 2 and 3 infections and 48 weeks in case of genotypes 1 and 4
      infections. Ribavirin was given 800mg in divided doses in case of genotypes 2 and
      3 infections and 1000mg-1200 mg in case of genotypes 1 and 4 infections according
      to body weight daily(1000 mg in divided doses if body weight <75kg and 1200mg in
      divided doses if body weight >75kg). Efficacy was assessed by measurements of
      serum HCV-RNA and serum ALT. A higher proportion of patients (71.87%) who
      received peginterferon alpha-2a plus ribavirin had a sustained virological
      response. It is observed that genotype 3 (a and b) patients showed poor response
      (SVR-47.05%), where as genotypes 1(a,b), 3 and 4 mixed, 2b and 4 infections
      showed response rate of 100%. So it can be concluded that once weekly
      peginterferon alpha-2a plus daily ribavirin is effective in chronic HCV infection
      in Bangladesh and overall response rate is similar to that reported in other
      studies. 

PMID- 24858164
TI  - Clinicopathologic features and treatment outcome of urinary bladder neoplasm.
AB  - More than ninety percent of bladder neoplasm is Transitional Cell Carcinoma
      (TCC). About 85% of patients present with symptom of painless haematuria. However
      haematuria is quite often intermittent so that a negative result has little
      meaning in ruling out the presence of bladder cancer. The present study was
      conducted to observe the natural history of different clinicopathologic stages of
      bladder cancer after transurethral resection bladder tumor (TURBT), either
      intravescical chemotherapy (IVC) or immunotherapy with BCG and of other forms of
      therapy like radio-chemotherapy (RCT) and radical surgery in few cases. A
      consecutive series of 52 cases with different grades and stages of bladder cancer
      patients were studied. Those who were noncompliant with surgery were sent for
      RCT. The age range of the patients was 34 to 75 with mean 53 year. Macroscopic
      haematuria, flank pain, microscopic haematuria, bladder irritability was found in
      43(82.7%), 06(11.5%), 03(5.8%), 32(61.5%) cases respectively and coincidental
      ureteral TCC with hydronephrosis was found in 04(7.7%) cases for whom radical
      nephreureterectomy and cystectomy with ileal conduit was done. Amongst the other
      muscle invasive tumor only three cases were compliant to do radical surgery; rest
      were advised to consult with oncologist for possible RCT. Superficial bladder
      cancer was 19(36.5%) and invasive bladder cancer was 33(63.5%). TURBT and IVT
      were offered for all superficial bladder tumors. Of them 06(31.5%) patients
      showed recurrence during the study period. More recurrences occur in IVC group
      (35.7%) than immunotherapy with BCG group (20%) Re-TURBT and stage wise treatment
      was offered to them. All recurrent cases were G-3 tumor and were multifocal.
      Recurrence rate is about 30%. Screening program and structured referral system
      should be developed to have early diagnosis for prompt treatment and best
      prognosis. 

PMID- 24858165
TI  - The quality of life of Sri Lankan patients with cutaneous leishmaniasis.
AB  - The effect of cutaneous leishmaniasis on the quality of life (QoL) in Sri Lankan
      patients' had not been evaluated before. This study was done to identify the
      factors resulting poor QoL in cutaneous leishmaniasis. The standard one-week
      Dermatology Life Quality Index (DLQI) questionnaire was used on 146 patients. The
      children <15 years of age, illiterates, who could not understand the
      questionnaire were excluded. Twenty one percent had no effect; overall 86% had
      DLQI <=10 indicating low/moderate effect. The least affected area was sexual
      function with some 92% stating they were not affected at all, while the areas of
      feelings, shopping, social, partner and treatment, (in descending order), being
      endorsed as the most affected areas. Facial lesions, lesions >=25mm diameter, 21
      40 age group were identified as being associated with poor QoL. Overall cutaneous
      leishmaniasis in Sri Lanka was a mild disease having low/moderate impact on 86%
      of patient's, in which 'feelings' being the most affected and 'sexual function'
      being the least affected domain. 

PMID- 24858166
TI  - Haemostatic effect of ecliptaalba on albino rabbits.
AB  - Ecliptaalba (Bhringraj) is an important traditional Indian medicinal plant
      reported to have antipyretic, anti-inflammatory, antihistaminic, hepatoprotective
      and anthelmintic effect well documented in literature. In the present study
      ethanolic leaf extract of eclipta alba (EEEA) was evaluated for its haemostatic
      activity by their ability to affect the screening test or modify the
      experimentally induced prolongation of test time on the basis of its folklore
      claim in normal, aspirin and heparin treated rabbits. The parameters recorded
      were BT, CT, PT and APTT & platelet count in all the three groups. The study was
      carried out in 3 parts in different doses 200,400,600 & 800mg/kg. Part-A-study of
      the haemostatic effect of Ethanolic extract of E. alba (EEEA) in graded doses on
      normal rabbits. Part-B-study of EEEA in aspirin treated rabbits. Part-C-study of
      EEEA in heparin treated rabbits. Tranexamic acid was used as the standard drug.
      Statistical analysis was performed using one way ANOVA & student t test. In
      normal rabbits EEEA high doses 800mg/k & 600mg/kg exhibited significant reduction
      in BT & CT (p<0.01). The same doses were found to decrease the aspirin induced
      increase in BT & heparin induced increase in CT in a significant manner (p<0.01).
      As decrease in CT might be due to liberation of some active principles from
      leaves of Ecliptaalba which demonstrated to have anti-haemorrhagic activity
      against snake bite not affecting any coagulation factor. No significant effect on
      PT, APPT and platelet count was observed. EEEA exhibited definite haemostatic
      effect in the above 3 sets of study. Phytochemical analysis and isolation of
      active principle is essential to carry on beneficial effects from laboratory
      bench to bedside of patients. 

PMID- 24858167
TI  - Liver dysfunction in alcoholics in Western Nepal.
AB  - To estimate liver function tests in patients with alcoholic fatty liver disease,
      alcoholic hepatitis and alcoholic cirrhosis and to compare the levels of enzymes
      between the groups. A hospital based case control study was carried out at
      Nepalgunj Medical College, Nepal from January 2013 to June 2013. A total of 150
      alcoholic associated liver disorders patients aged between 20-70 years and 50 sex
      age matched normal healthy controls were taken to assess liver function tests
      (LFTs) by measuring Aspartate aminotransferase (AST), Alanine aminotransferase
      (ALT), Alkaline phosphatase (ALP), Gamma glutamyltranspeptidase (GGT) & Albumin.
      The mean+/-SD of liver function tests (LFTs) of patients of alcoholic fatty liver
      disease is highest followed by alcoholic hepatitis patients. All the 3 groups of
      alcoholic associated liver disorders patients when compared to normal healthy
      control subjects showed statistically significant increase in the levels of AST
      (p<0.000), ALT (p<0.000), ALP (p<0.006), GGT (p<0.000), & Albumin (p<0.000).
      Liver function tests values for alcoholic associated liver disorders patients
      when compared to the healthy control subjects was significantly altered. 

PMID- 24858168
TI  - Miliary nodules in a patient of allergic bronchopulmonary aspergilosis.
AB  - Allergic bronchopulmonary aspergilosis (ABPA) is immunological pulmonary disease
      caused by hypersensitivity of aspergillus fumigatus usually occurs in patients
      with chronic asthma, cystic fibrosis and bronchiactasis. This disease may present
      with divers radiological presentation like; fleeting pulmonary opacities,
      bronchiactasis, mucoid impaction, perihilar opacity (hailer lymphadenopathy), and
      lung mass or pleural effusion. We describe the case of a 30 year old housewife
      who presented with progressive dysponea, low grade fever, dry cough, weight loss
      and miliary nodule in chest radiograph and high-resolution CT (HRCT) in a
      tertiary level hospital of Bangladesh. A diagnosis of ABPA was established on the
      basis of sputum routine microscopy and culture examination for fungus
      (Aspergillus). 

PMID- 24858169
TI  - Cutaneous anthrax in a school teacher.
AB  - Cutaneous anthrax is an infection of the skin caused by Bacillus anthracis. This
      is a report of a case of cutaneous anthrax attending outpatients of Mymensingh
      Medical College Hospital in October, 2010. The infected person was a retired
      school teacher with a very good body build. He reported to handle cow flesh about
      4-5 days ago, developed few painless papules over shin of right leg, which
      gradually became large bullae and blackish eschar developed over the lesion.
      Smears from the lesions were investigated which confirmed the causative agent B.
      anthracis. The patient was treated with oral Ciprofloxacin (500mg) twice daily
      for seven days which cured the infection as observed on his subsequent follow up
      visits on 7 and 14 days later. Oral Ciprofloxacin is found effective as
      recommended by the World Health Organization. 

PMID- 24858170
TI  - Primary hyperparathyroidism: a case report.
AB  - Primary hyperparathyroidism results from the excessive secretion of PTH and
      typically produces frank hypercalcaemia. With the advent of multiphasic screening
      of serum chemistries, it has been recognized that primary hyperparathyroidism is
      not an uncommon disorder. Here, a 32 years old lady with burning to colicky
      recurrent upper abdominal pain, polyuria, polydipsia associated with anorexia,
      dyspepsia, generalized body ache, joint pain, constipation and weight loss has
      been described. An initial abdominal ultrasound was performed at hospital and
      revealed features of cholelithiasis and bilateral nephrocalcinosis. Serum
      biochemistries revealed that her serum calcium was 12.60mg/dl, serum PTH was
      222.80ng/dl, serum creatinine was 0.90mg/dl, 99 Tc-sestamibi scanning for
      parathyroid evaluation revealed features suggestive of parathyroid adenoma
      adjoining the lower pole of right lobe of thyroid gland. Bone densitometry of
      femur and spine by DEXA showed osteoporosis with T score value <-3.5 SD. Right
      hemithyroidectomy with parathyroid adenoma excision was performed. Patient was
      closely monitored. Serum calcium and parathyroid hormone levels were markedly
      reduced near to the normal range within two weeks of surgery. Following five
      months after surgery, serum PTH was 29.59ng/dl, six months after surgery serum
      calcium was 9.2mg/dl. Patient is now in good physical condition and under regular
      follow up. 

PMID- 24858171
TI  - Primary adrenal leiomyosarcoma in an adult female.
AB  - Primary leiomyosarcoma of the adrenal gland is a rare tumour and we describe such
      a case in a 35 year old female who had dull pain in the left flank for 6 months.
      There was no weight loss or fever only mild tenderness was in the left subcostal
      region. She was normotensive and there was no evidence of virilization. CT scan
      revealed left adrenal mass, after adrenalectomy it was 8.5*7.5*6.2cm3 in size.
      There was no evidence of local extension or metastasis. Histopathology confirmed
      adrenal leiomyosarcome. 

PMID- 24858172
TI  - Malignant paraganglioma: a case report.
AB  - A paraganglioma is a rare tumour composed of chromaffin cells. The malignant
      paraganglioma is a very rare presentation, diagnosed by local recurrence after
      total resection of primary mass or findings of distant metastasis. Recurrent
      paraganglioma developed in a 60 years old lady 10 years after first surgical
      resection. This time the patient presented with neck swelling as well as with
      vertebral metastases. The patient underwent radiotherapy and symptomatic
      improvement was there. We present the case to emphasize the role of imaging in
      early diagnosis, avoidance of complications of advanced disease and to make
      awareness among the physicians. 

PMID- 24858173
TI  - A case of abdominal wall scar endometriosis.
AB  - Endometriosis is presence of functioning endometrial tissue outside the uterine
      cavity. Endometriosis can sometimes occur in a previous surgical scar. Scar
      endometriosis is rare and difficult to diagnose. It mostly follows obstetrical
      and gynecological surgeries. This condition is often confused with other surgical
      conditions. We are reporting a case of scar endometriosis following caesarean
      section, which was being treated as stitch granuloma for long time. Medical
      treatment was not helpful. The patient required wide surgical excision of the
      lesion. Now the patient is under regular follow up, because there is chance of
      recurrence. 

PMID- 24858174
TI  - Solid pseudopapillary tumour of pancreas.
AB  - Solid pseudopapillary tumour of pancreas (SPT) is an extremely rare pancreatic
      tumour, which has a low malignant potential and occurs mainly in young women.
      Pathologic and imaging findings include a well defined encapsulated pancreatic
      mass with cystic and solid components with evidence of haemorrhage. This is a
      case of a 16 years old girl who presented with upper abdominal pain of long
      duration and epigastric mass on palpation. Computed Tomography (CT) scan
      demonstrated a large well defined heterogenous attenuation mass of solid
      enhancing and cystic non enhancing areas, arising from the head of the pancreas.
      Radiologically it was diagnosed as a case of pancreatic neoplasm. Fine needle
      aspiration cytology (FNAC) and histopathology of the biopsy material diagnosed as
      solid pseudopapillary tumour of pancreas. 

PMID- 24858175
TI  - Pregnancy with myasthenia gravis.
AB  - Myasthenia gravis (MG) is an autoimmune disorder of the neuromuscular
      transmission, caused by auto antibodies against the nicotinic acetylcholine
      receptor. These antibodies of the IgG isotype are detected in 80-90% of
      generalized MG and in 50-70% of ocular MG. Seronegative MG is caused by humoral
      factors. Prevalence of MG lies between 1 in 10.000 and 1 in 50.000, with 2/3 of
      affected individuals being female. In the case of maternal myasthenia gravis,
      both the mother and the child may develop myasthenia symptoms with varying
      degrees of weakness and progressive fatigability of the skeletal muscles. Data
      for the case report were generated by reviewing labour, delivery, and postpartal
      records. We present a 26 years old lady who suffered from a generalized form of
      myasthenia gravis since the age of 15. She got herself admitted to a neurologic
      clinic for a myasthenic crisis when she was two and half months pregnant. The
      patient was treated with anticholinesterase medication, corticosteroids and
      intravenous immunoglobulin. Clinically, the patient's condition improved
      significantly during pregnancy. Delivery and the post delivery period were also
      normal for the patient. Myasthenia gravis especially when associated with
      pregnancy is a high-risk disease. As this disease predominantly occurs in women
      of reproductive age, it is important to be aware of this condition in obstetrics
      and its interdisciplinary diagnostic and therapeutic management is required. 

PMID- 24858176
TI  - Neonatal uterine prolapse - a case report.
AB  - Uterine prolapse is commonly seen in the geriatric age group. Congenital
      vaginouterine prolapse is a rare condition occurring in neonates and is usually
      associated with spinal cord malformations in about 85% of cases. Several
      modalities of treatment have been described for neonatal uterine prolapse.
      Conservative treatment in the form of simple digital reposition, use of pessary
      or other self-retaining device is usually sufficient to treat this condition,
      which is self-limiting and regressive. Here we report our first case of neonatal
      uterine prolapse, managed successfully with simple digital reposition. 

PMID- 24858177
TI  - Electroencephalogram (EEG) in the management of epilepsy in children.
AB  - Electroencephalogram (EEG) has an important role in the management of seizure
      disorder in children. It helps in diagnosis and classification of epilepsy,
      choosing of antiepileptic medication and prediction of prognosis. When history of
      epilepsy is unclear, EEG can help to distinguish epileptiform discharges from its
      counterpart. But EEG has limitations. In epilepsy, EEG has variable range of
      sensitivity and specificity. Hereby, during interpretation of EEG, clinical
      situation should not be ignored. Interictal EEG has important diagnostic and
      prognostic value in epilepsy. But caution is needed during evaluation of
      significance of interictal epileptiform discharge (IED). Methods like recording
      of EEG in awake and sleep state, hyperventilation and photic stimulation enhances
      the yield of interictal EEG. Long term EEG recording has an important role in the
      assessment of patients who present diagnostic or management difficulties
      following clinical evaluation and routine EEG. 

PMID- 24858178
TI  - Second trimester sonographic features of fetal chromosomal defects.
AB  - Advances in ultrasound technology have dramatically improved the detection of
      fetal chromosomal defects. Each chromosomal defect has its own syndromal pattern
      of detectable abnormalities prenataly. Most commonly detectable defects are
      Trisomies & Triploidies. Although only an invasive test can provide a definitive
      diagnosis, fetuses with major chromosomal abnormalities have either external or
      internal defects that can be recognized by detailed ultrasonographic examination
      at second trimester. These are defined as ultrasound markers for fetal
      aneuploidy. This article provides an overview and discussion on prenatal
      sonographic features that may suggest the presence of a common fetal chromosomal
      defect. 

PMID- 24858179
TI  - Extending the evidence base for prolonged exposure: significant effectiveness
      noted with sexual abuse-related PTSD in adolescent girls.

PMID- 24858180
TI  - The role of cellular senescence on the cyclic stretching-mediated activation of
      MAPK and ALP expression and activity in human periodontal ligament fibroblasts.
AB  - Mechanical loading is considered to be a major parameter of the periodontal
      ligament (PDL) remodeling and differentiation. However, the molecular mechanisms
      that translate these forces to cellular responses are not fully elucidated.
      Especially, although aging affects PDL homeostasis, the role of cellular
      senescence on the activation of signaling pathways in periodontal ligament
      fibroblasts (PDLF) in response to mechanical stimulation has not been studied
      yet. Here, we present evidence showing that cyclic mechanical stimulation
      activates ERK, JNK and p38 MAPK in young (early-passage) human PDLF, in a RhoK
      dependent manner. This response was found to be independent of the substratum
      (i.e. fibronectin or collagen) on which these cells grow. Stretching up-regulates
      also c-fos, a classical cellular response to mechanical deformation. Inhibition
      of ERK and JNK reduces, while that of p38 enhances stress-mediated c-fos
      expression. In addition, cyclic stretching stimulates the expression and activity
      of alkaline phosphatase (ALP), an early marker of osteoblastic differentiation.
      We have recently shown that senescent human PDLF have a significantly decreased
      expression of ALP, linked to an inability towards osteoblastic differentiation.
      Here, we found that senescent PDLF are able to respond to cyclic mechanical
      stretching by activating ERK, JNK and p38 MAPK, with similar kinetics compared to
      young cells, and by up-regulating c-fos and ALP expression and activity. However,
      even after stimulation, ALP levels in senescent cells are still much lower
      compared to the basal levels of their young counterparts, suggesting that
      senescence impairs the differentiation of human PDLF when subjected to cyclic
      mechanical deformation. 

PMID- 24858181
TI  - Arrhythmogenic effects by local left ventricular stretch: effects of flecainide
      and streptomycin.
AB  - Mechanical stretch has been shown to provoke arrhythmia. We wanted to analyze
      ventricular arrhythmia induced by local left ventricular stretch in order to find
      out, where arrhythmias originate and whether they can be prevented
      pharmacologically. Isolated rabbit hearts (Langendorff technique) were submitted
      to increased left ventricular stretch at the left wall by insertion of an
      additional intraventricular balloon and adjusting the end-diastolic pressure
      (EDP) to 25 mmHg for 10 min followed by 20 min recovery at normal EDP of 5-8
      mmHg. Activation and repolarization processes were investigated by ventricular
      256 electrode epicardial mapping. The hearts were treated during the whole
      procedure either with vehicle, 0.5 MUM flecainide (sodium channel blocker) or 100
      MUM streptomycin (here used as stretch-activated ion-channel blocker). In
      addition, we performed a series of experiments, in which we enhanced EDP to 30
      mmHg (global stretch instead of local stretch) by inflating the left ventricular
      pressure balloon (strain, 0.148 +/- 0.034). Each series was performed with n = 6.
      Stretch resulted in local strain of 25% at the left wall together with a local
      slowing of the activation process at the left wall, in a change in the activation
      pattern, and in ventricular arrhythmia. Coronary flow was not affected.
      Ventricular arrhythmias originated from the border between the stretched area and
      the non-stretched region. Flecainide and streptomycin reduced the prolongation of
      the activation process at the stretched left wall and mitigated the difference in
      total activation time between left and front wall but only partially prevented
      arrhythmia. In the additional global stretch experiments relative coronary flow
      and the other parameters remained unchanged, in particular TAT. Thus, in contrast
      to the local stretch series, there was no difference in the change in TAT between
      left and front wall. Only rare single ventricular extrasystoles (<1/min;
      originating from LV (front and left wall) i.e. from within the stretched region)
      were seen during stretch (but not at the beginning) and during recovery. Local
      left ventricular stretch can elicit ventricular arrhythmias. Local slowing of
      electrical activation seems involved so that the difference in total activation
      time of the stretched free left wall and the non-stretched increased.

PMID- 24858183
TI  - Painful scoliosis due to superposed giant cell bone tumor and aneurysmal bone
      cyst in a child.
AB  - Giant cell bone tumors are the most common precursor lesions of aneurysmal bone
      cysts (ABCs) developing secondarily. In giant cell bone tumors containing an
      explicit ABC component, the observation of the solid component of the giant cell
      bone tumor plays a critical role in the separation of the primary ABC. In
      general, ABC cases together with giant cell tumors in the bone are diagnosed
      histopathologically. The combination of giant cell bone tumor with superposed ABC
      and that of painful scoliosis with backache is rarely seen in children. In this
      case study, we discussed the diagnosis and the treatment of a giant cell tumor
      and superposed an ABC present in the fifth lumbar spine in a pediatric patient
      admitted to our clinic with a complaint of acute scoliotic back pain.

PMID- 24858182
TI  - From ventral-medial to dorsal-lateral striatum: neural correlates of reward
      guided decision-making.
AB  - The striatum is critical for reward-guided and habitual behavior. Anatomical and
      interference studies suggest a functional heterogeneity within striatum. Medial
      regions, such as nucleus accumbens core and dorsal medial striatum play roles in
      goal-directed behavior, while dorsal lateral striatum is critical for control of
      habitual action. Subdivisions of striatum are topographically connected with
      different cortical and subcortical structures forming channels that carry
      information related to limbic, associative, and sensorimotor functions. Here, we
      describe data showing that as one progresses from ventral-medial to dorsal
      lateral striatum, there is a shift from more prominent value encoding to activity
      more closely related to associative and motor aspects of decision-making. In
      addition, we will describe data suggesting that striatal circuits work in
      parallel to control behavior and that regions within striatum can compensate for
      each other when functions are disrupted. 

PMID- 24858184
TI  - Response to 'Comment on the article 'The biomechanics of guided growth: does
      screw size, plate size, or screw configuration matter?' by Schoenleber et al.'.

PMID- 24858185
TI  - Influence of the AgrC-AgrA complex on the response time of Staphylococcus aureus
      quorum sensing.
AB  - The Staphylococcus aureus agr quorum-sensing system plays a major role in the
      transition from the persistent to the virulent phenotype. S. aureus agr type I to
      IV strains are characterized by mutations in the sensor domain of the histidine
      kinase AgrC and differences in the sequences of the secreted autoinducing
      peptides (AIP). Here we demonstrate that interactions between the cytosolic
      domain of AgrC (AgrCCyto) and the response regulator domain of AgrA (AgrARR)
      dictate the spontaneity of the cellular response to AIP stimuli. The crystal
      structure of AgrCCyto provided a basis for a mechanistic model of AgrC-AgrA
      interactions. This model enabled an analysis of the biochemical and biophysical
      parameters of AgrC-AgrA interactions in the context of the conformational
      features of the AgrC-AgrA complex. This analysis revealed distinct sequence and
      conformational features that determine the affinity, specificity, and kinetics of
      the phosphotransfer reaction. This step, which governs the response time for
      transcriptional reengineering triggered by an AIP stimulus, is independent of the
      agr type and similar for agonist and antagonist stimuli. These experimental data
      could serve as a basis on which to validate simulations of the quorum-sensing
      response and for strategies that employ the agr quorum-sensing system to combat
      biofilm formation in S. aureus infections. 

PMID- 24858186
TI  - Genetic requirements for sensitivity of bacteriophage t7 to dideoxythymidine.
AB  - We previously reported that the presence of dideoxythymidine (ddT) in the growth
      medium selectively inhibits the ability of bacteriophage T7 to infect Escherichia
      coli by inhibiting phage DNA synthese (N. Q. Tran, L. F. Rezende, U. Qimron, C.
      C. Richardson, and S. Tabor, Proc. Natl. Acad. Sci. U. S. A. 105:9373-9378, 2008,
      doi:10.1073/pnas.0804164105). In the presence of T7 gene 1.7 protein, ddT is
      taken up into the E. coli cell and converted to ddTTP. ddTTP is incorporated into
      DNA as ddTMP by the T7 DNA polymerase, resulting in chain termination. We have
      identified the pathway by which exogenous ddT is converted to ddTTP. The pathway
      consists of ddT transport by host nucleoside permeases and phosphorylation to
      ddTMP by the host thymidine kinase. T7 gene 1.7 protein phosphorylates ddTMP and
      ddTDP, resulting in ddTTP. A 74-residue peptide of the gene 1.7 protein confers
      ddT sensitivity to the same extent as the 196-residue wild-type gene 1.7 protein.
      We also show that cleavage of thymidine to thymine and deoxyribose-1-phosphate by
      the host thymidine phosphorylase greatly increases the sensitivity of phage T7 to
      ddT. Finally, a mutation in T7 DNA polymerase that leads to discrimination
      against the incorporation of ddTMP eliminates ddT sensitivity. 

PMID- 24858188
TI  - Here we go again: bullying history and cardiovascular responses to social
      exclusion.
AB  - Previous research suggests that social exclusion-both acute and chronic-may be
      associated with a pattern of blunted cardiovascular responding. But it is unknown
      to what extent acute and chronic exclusion interact. That is, what happens when
      victims of long-term social rejection encounter an instance of exclusion later in
      life? The goal of the present study was to test whether prior experience being
      bullied would alter cardiovascular responses to an acute experience of social
      exclusion. Participants took part in a short online chat, during which they were
      either included or excluded from the conversation. Consistent with hypotheses,
      all participants showed an increase in sympathetic activity in the exclusion
      condition, but this response was significantly blunted among those with more
      chronic history of bullying victimization. No differences were observed for
      parasympathetic activity. This pattern suggests that a history of chronic
      victimization magnifies the cardiovascular "blunting" shown previously among
      victims of ostracism. This line of work suggests that bullying victims may
      develop regulatory mechanisms in response to social threats, and this may
      ultimately provide valuable information for helping victims become more
      resilient. 

PMID- 24858187
TI  - Identification and characterization of a novel secreted glycosidase with multiple
      glycosidase activities in Streptococcus intermedius.
AB  - Streptococcus intermedius is a known human pathogen and belongs to the anginosus
      group (S. anginosus, S. intermedius, and S. constellatus) of streptococci (AGS).
      We found a large open reading frame (6,708 bp) in the lac operon, and
      bioinformatic analysis suggested that this gene encodes a novel glycosidase that
      can exhibit beta-d-galactosidase and N-acetyl-beta-d-hexosaminidase activities.
      We, therefore, named this protein "multisubstrate glycosidase A" (MsgA). To test
      whether MsgA has these glycosidase activities, the msgA gene was disrupted in S.
      intermedius. The msgA-deficient mutant no longer showed cell- and supernatant
      associated beta-d-galactosidase, beta-d-fucosidase, N-acetyl-beta-d
      glucosaminidase, and N-acetyl-beta-d-galactosaminidase activities, and all
      phenotypes were complemented in trans with a recombinant plasmid carrying msgA.
      Purified MsgA had all four of these glycosidase activities and exhibited the
      lowest Km with 4-methylumbelliferyl-linked N-acetyl-beta-d-glucosaminide and the
      highest kcat with 4-methylumbelliferyl-linked beta-d-galactopyranoside. In
      addition, the purified LacZ domain of MsgA had beta-d-galactosidase and beta-d
      fucosidase activities, and the GH20 domain exhibited both N-acetyl-beta-d
      glucosaminidase and N-acetyl-beta-d-galactosaminidase activities. The beta-d
      galactosidase and beta-d-fucosidase activities of MsgA are thermolabile, and the
      optimal temperature of the reaction was 40 degrees C, whereas almost all
      enzymatic activities disappeared at 49 degrees C. The optimal temperatures for
      the N-acetyl-beta-d-glucosaminidase and N-acetyl-beta-d-galactosaminidase
      activities were 58 and 55 degrees C, respectively. The requirement of sialidase
      treatment to remove sialic acid residues of the glycan branch end for glycan
      degradation by MsgA on human alpha1-antitrypsin indicates that MsgA has
      exoglycosidase activities. MsgA and sialidase might have an important function in
      the production and utilization of monosaccharides from oligosaccharides, such as
      glycans for survival in a normal habitat and for pathogenicity of S. intermedius.

PMID- 24858189
TI  - Prevalence, morbidity, and mortality patterns of typhoid ileal perforation as
      seen at the University of Nigeria Teaching Hospital Enugu Nigeria: an 8-year
      review.
AB  - BACKGROUND: Some recent studies have reported a decrease in mortality from
      typhoid ileal perforation. The present report aims to determine the prevalence,
      morbidity, and mortality of this disease in patients mostly drawn from a rural
      area. METHODS: This is a retrospective study of 50 patients treated between
      January 1999 and December 2007 at the University of Nigeria Teaching Hospital,
      Enugu, Nigeria. The variables studied included patient demographics, clinical
      features, intraoperative findings, complications, and mortality. Statistical
      analysis was done with SPSS version 13. RESULTS: Of the 50 patients included in
      the study, 22 were males with the highest rate in patients aged 20 years and
      younger. Fever was the commonest symptom and at initial presentation, the mean
      pulse and respiratory rates were significantly higher in the patients who
      subsequently died than in those who survived (P < 0.05). All the perforations
      occurred in the ileum; 62 % of the patients had solitary perforations, 28 % had
      double perforations, and 10 % had three or more. Fifty-eight perforations were
      treated by simple closure in two layers, 4 patients had ileal resection and
      anastomosis, and 2 underwent right hemicolectomy. The mean interval between
      operation and death was 1.7 days. The overall mortality rate was 30 %, but among
      those with three or more perforations, mortality was 100 %. CONCLUSIONS: Typhoid
      ileal perforation still carries a high mortality especially in rural areas. Those
      with tachycardia and tachypnea at presentation and those with three or more
      perforations are at a higher risk of dying from the disease.

PMID- 24858190
TI  - Pancreaticoduodenal resection for malignancy in a low-volume center: long-term
      outcomes from a developing country.
AB  - BACKGROUND: The technical complexity of pancreatic resection has made it a
      specialized procedure performed in high-volume centers. It has been shown that
      patients operated on in high-volume pancreatobiliary centers have fewer
      complications and better survival. The purpose of this study was to share our
      experience with and report long-term outcomes of pancreaticoduodenal resections
      performed in a low-volume center in Pakistan. METHODS: Data of patients who
      underwent pancreaticoduodenal resection for adenocarcinoma at our institute from
      1999 to 2012 were reviewed. A total of 39 patients were included in the study.
      Variables included patients' clinical and histopathological characteristics.
      Outcome was determined based on complication rate, 30- and 90-day mortality,
      disease-free survival, and overall survival. For survival analysis, Kaplan-Meier
      curves were used and significance was determined using a log rank test.
      Univariate Cox analysis was performed to determine significant factors for
      multivariate analysis. RESULTS: The majority of tumors [20 (51 %)] were moderate
      grade, T1/T2 [20 (51 %)], ampullary adenocarcinomas [18 (46 %)]. Mean hospital
      stay was 14 +/- 8 days. The mean number of nodes removed was 13.9 +/- 6.9, while
      mean number of positive nodes was 1 +/- 1.7. Expected 5-year overall survival and
      relapse-free survival were 38 and 48 %, respectively. Overall 5-year survival was
      significantly different with respect to nodal involvement, i.e., 47 vs. 28 % (P =
      0.018). On univariate analysis, nodal involvement was the only factor associated
      with an increased risk of death (P = 0.02, hazard ratio [HR] 2.9, confidence
      interval [CI] 1.1-7.8). CONCLUSION: Low-volume centers are an acceptable
      alternate to high-volume centers for performing pancreaticoduodenal resection in
      carefully selected patients. Efforts should be directed at developing specialized
      hepatobiliary centers in developing countries.

PMID- 24858191
TI  - Combination of morphologic criteria and alpha-fetoprotein in selection of
      patients with hepatocellular carcinoma for liver transplantation minimizes the
      problem of posttransplant tumor recurrence.
AB  - BACKGROUND: Serum alpha-fetoprotein concentration (AFP) might be a useful
      addition to morphologic criteria for selecting patients with hepatocellular
      carcinoma (HCC) for liver transplantation (LT). The aim of this study was to
      evaluate the role of AFP in selecting HCC patients at minimal risk of
      posttransplant tumor recurrence in the setting of existing criteria. METHODS:
      This retrospective cohort study was based on 121 HCC patients after LT performed
      at a single institution. AFP was evaluated as a predictor of posttransplant tumor
      recurrence with respect to fulfillment of the Milan, University of California,
      San Francisco (UCSF), and Up-to-7 criteria. RESULTS: There was a nearly linear
      association between AFP and the risk of HCC recurrence (p < 0.001 for linear
      effect; p = 0.434 for nonlinear effect). AFP predicted HCC recurrence in patients
      (1) beyond the Milan criteria (p < 0.001; optimal cutoff 200 ng/ml); (2) within
      the UCSF criteria (p = 0.001; optimal cutoff 100 ng/ml) and beyond them (p =
      0.015; optimal cutoff 200 ng/ml); and (3) within the Up-to-7 criteria (p = 0.001;
      optimal cutoff 100 ng/ml) and beyond them (p = 0.023; optimal cutoff 100 ng/ml)
      but not in patients within the Milan criteria (p = 0.834). Patients within either
      UCSF and Up-to-7 criteria with AFP level <100 ng/ml exhibited superior (100 %) 5
      year recurrence-free survival-significantly higher than those within UCSF (p =
      0.005) or Up-to-7 (p = 0.001) criteria with AFP levels higher than the estimated
      cutoffs or beyond with AFP levels less than the estimated cutoffs. CONCLUSIONS:
      Combining the UCSF and Up-to-7 criteria with an AFP level <100 ng/ml is
      associated with minimal risk of tumor recurrence. Hence, this combination might
      be useful for selecting HCC patients for LT.

PMID- 24858193
TI  - Asymptomatic Plasmodium falciparum malaria in pregnant women in the Chittagong
      Hill Districts of Bangladesh.
AB  - BACKGROUND: Pregnancy is a known risk factor for malaria which is associated with
      increased maternal and infant mortality and morbidity in areas of moderate-high
      malaria transmission intensity where Plasmodium falciparum predominates. The
      nature and impact of malaria, however, is not well understood in pregnant women
      residing in areas of low, unstable malaria transmission where P. falciparum and
      P. vivax co-exist. METHODS: A large longitudinal active surveillance study of
      malaria was conducted in the Chittagong Hill Districts of Bangladesh. Over 32
      months in 2010-2013, the period prevalence of asymptomatic P. falciparum
      infections was assessed by rapid diagnostic test and blood smear and compared
      among men, non-pregnant women and pregnant women. A subset of samples was tested
      for infection by PCR. Hemoglobin was assessed. Independent risk factors for
      malaria infection were determined using a multivariate logistic regression model.
      RESULTS: Total of 34 asymptomatic P. falciparum infections were detected by
      RDT/smear from 3,110 tests. The period prevalence of asymptomatic P. falciparum
      infection in pregnant women was 2.3%, compared to 0.5% in non-pregnant women and
      0.9% in men. All RDT/smear positive samples that were tested by PCR were PCR
      positive, and PCR detected additional 35 infections that were RDT/smear negative.
      In a multivariate logistic regression analysis, pregnant women had 5.4-fold
      higher odds of infection as compared to non-pregnant women. Malaria-positive
      pregnant women, though asymptomatic, had statistically lower hemoglobin than
      those without malaria or pregnancy. Asymptomatic malaria was found to be evenly
      distributed across space and time, in contrast to symptomatic infections which
      tend to cluster. CONCLUSION: Pregnancy is a risk factor for asymptomatic P.
      falciparum infection in the Chittagong Hill Districts of Bangladesh, and
      pregnancy and malaria interact to heighten the effect of each on hemoglobin. The
      even distribution of asymptomatic malaria, without temporal and spatial
      clustering, may have critical implications for malaria elimination strategies.

PMID- 24858194
TI  - Hindlimb motion during steady flight of the lesser dog-faced fruit bat,
      Cynopterus brachyotis.
AB  - In bats, the wing membrane is anchored not only to the body and forelimb, but
      also to the hindlimb. This attachment configuration gives bats the potential to
      modulate wing shape by moving the hindlimb, such as by joint movement at the hip
      or knee. Such movements could modulate lift, drag, or the pitching moment. In
      this study we address: 1) how the ankle translates through space during the
      wingbeat cycle; 2) whether amplitude of ankle motion is dependent upon flight
      speed; 3) how tension in the wing membrane pulls the ankle; and 4) whether wing
      membrane tension is responsible for driving ankle motion. We flew five
      individuals of the lesser dog-faced fruit bat, Cynopterus brachyotis (Family:
      Pteropodidae), in a wind tunnel and documented kinematics of the forelimb, hip,
      ankle, and trailing edge of the wing membrane. Based on kinematic analysis of
      hindlimb and forelimb movements, we found that: 1) during downstroke, the ankle
      moved ventrally and during upstroke the ankle moved dorsally; 2) there was
      considerable variation in amplitude of ankle motion, but amplitude did not
      correlate significantly with flight speed; 3) during downstroke, tension
      generated by the wing membrane acted to pull the ankle dorsally, and during
      upstroke, the wing membrane pulled laterally when taut and dorsally when
      relatively slack; and 4) wing membrane tension generally opposed dorsoventral
      ankle motion. We conclude that during forward flight in C. brachyotis, wing
      membrane tension does not power hindlimb motion; instead, we propose that
      hindlimb movements arise from muscle activity and/or inertial effects. 

PMID- 24858195
TI  - Metal complexes of ONO donor Schiff base ligand as a new class of bioactive
      compounds: synthesis, characterization and biological evolution.
AB  - Present work reviews that, the synthesis of (E)-N'-((7-hydroxy-4-methyl-2-oxo-2H
      chromen-8-yl)methylene)benzohydrazide [L] ligand and their metal complexes. The
      colored complexes were prepared of type [M(2+)L]X2, where M(2+)=Mn, Co, Ni, Cu,
      Sr and Cd, L=(7-hydroxy-4-methyl-2-oxo-2H-chromen-8-yl)methylene)benzohydrazide,
      X=Cl(-). Ligand derived from the condensation of 8-formyl-7-hydroxy-4
      methylcoumarin and benzohydrazide in the molar ratio 1:1 and in the molar ratio
      1:2 for metal complexes have been prepared. The chelation of the ligand to metal
      ions occurs through the both oxygen groups, as well as the nitrogen atoms of the
      azomethine group of the ligand. Reactions of the Schiff base ligand with
      Manganese(II), Cobalt(II), Nickel(II), Copper(II), Strontium(II), and Cadmium(II)
      afforded the corresponding metal complexes. The structures of the obtained ligand
      and their respective metal complexes were elucidated by infra-red, elemental
      analysis, Double beam UV-visible spectra, conductometric measurements, magnetic
      susceptibility measurements and also thermochemical studies. The metal complex
      exhibits octahedral coordination geometrical arrangement. Schiff base ligand and
      their metal complexes were tested against antioxidants, antidiabetic and
      antimicrobial activities have been studied. The Schiff base metal complexes
      emerges effective alpha-glucosidase inhibitory activity than free Schiff base
      ligand. 

PMID- 24858196
TI  - Adaptive neuro-fuzzy inference system model for adsorption of 1,3,4-thiadiazole
      2,5-dithiol onto gold nanoparticales-activated carbon.
AB  - In this research, a novel adsorbent gold nanoparticle loaded on activated carbon
      (Au-NP-AC) was synthesized by ultrasound energy as a low cost routing protocol.
      Subsequently, this novel material characterization and identification followed by
      different techniques such as scanning electron microscope(SEM), Brunauer-Emmett
      Teller(BET) and transmission electron microscopy (TEM) analysis. Unique
      properties such as high BET surface area (>1229.55m(2)/g) and low pore size
      (<22.46A) and average particle size lower than 48.8A in addition to high reactive
      atoms and the presence of various functional groups make it possible for
      efficient removal of 1,3,4-thiadiazole-2,5-dithiol (TDDT). Generally, the
      influence of variables, including the amount of adsorbent, initial pollutant
      concentration, contact time on pollutants removal percentage has great effect on
      the removal percentage that their influence was optimized. The optimum parameters
      for adsorption of 1,3,4-thiadiazole-2, 5-dithiol onto gold nanoparticales
      activated carbon were 0.02g adsorbent mass, 10mgL(-1) initial 1,3,4-thiadiazole
      2,5-dithiol concentration, 30min contact time and pH 7. The Adaptive neuro-fuzzy
      inference system (ANFIS), and multiple linear regression (MLR) models, have been
      applied for prediction of removal of 1,3,4-thiadiazole-2,5-dithiol using gold
      nanoparticales-activated carbon (Au-NP-AC) in a batch study. The input data are
      included adsorbent dosage (g), contact time (min) and pollutant concentration
      (mg/l). The coefficient of determination (R(2)) and mean squared error (MSE) for
      the training data set of optimal ANFIS model were achieved to be 0.9951 and
      0.00017, respectively. These results show that ANFIS model is capable of
      predicting adsorption of 1,3,4-thiadiazole-2,5-dithiol using Au-NP-AC with high
      accuracy in an easy, rapid and cost effective way. 

PMID- 24858197
TI  - Reply: To PMID 24096182.

PMID- 24858198
TI  - Adhesion prevention after cesarean delivery: evidence, and lack of it.
AB  - In spite of the recognized occurrence of cesarean-attributable adhesions, its
      clinical significance is uncertain. The presence of adhesions during a repeat
      cesarean section can make fetal extraction lengthy and the procedure challenging
      and may increase the risk of injury to adjacent organs. Two methods for adhesion
      prevention are discussed, peritoneal closure and use of adhesion barriers.
      Peritoneal closure appears to be safe in the short term. In the long term,
      conflicting evidence arise from reviewing the literature for possible adhesion
      reduction benefits. A systematic review of the literature on the use of adhesion
      barriers in the context of cesarean section yielded only a few studies, most of
      which are lacking in methodology. For now, it appears that the available evidence
      does not support the routine use of adhesion barriers during cesarean delivery. 

PMID- 24858199
TI  - Response to publication entitled: High-risk human papillomavirus at entry to
      prenatal care and risk of preeclampsia, McDonnold et al.

PMID- 24858200
TI  - Use of the combined tetanus-diphtheria and pertussis vaccine during pregnancy.
AB  - OBJECTIVE: A recent increase in pertussis cases prompted the Advisory Committee
      on Immunization Practices to recommend administering the perinatal tetanus,
      diphtheria, and pertussis (Tdap) vaccine during each pregnancy. We sought to
      describe uptake of Tdap and identify predictors of vaccination in pregnancy.
      STUDY DESIGN: We conducted a retrospective study of all women delivering at a
      university hospital between February and June 2013. Demographic, pregnancy, and
      vaccination data were abstracted from the medical record. The relationship
      between maternal age, parity, gestational age, race/ethnicity, marital status,
      prenatal provider/site, insurance, influenza vaccination status, and Tdap vaccine
      was described by univariate analysis. Independent predictors were identified by
      multivariable logistic regression. RESULTS: In our cohort of 1467 women, 1194
      (81.6%) received a Tdap vaccine. After adjusting for potential confounders, 3
      factors were found to be independent predictors of receiving the vaccine.
      Patients were more likely to receive Tdap if they had been vaccinated against
      influenza during this pregnancy (adjusted odds ratio [aOR], 1.7; 95% confidence
      interval [CI], 1.4-2.3). Black women were less likely to receive Tdap when
      compared with other women (aOR, 0.42; 95% CI, 0.27-0.67). Also, women who
      delivered preterm were less likely to receive the Tdap vaccine (aOR, 0.33; 95%
      CI, 0.22-0.48). CONCLUSION: A high overall Tdap vaccination rate was observed
      following implementation of the Advisory Committee on Immunization Practices
      guidelines. Black women, however, had significantly lower vaccine uptake than
      other women. Further research is needed to understand and minimize this
      disparity. Women who delivered prematurely also had a decreased rate of Tdap
      vaccination; vaccinating earlier should be considered to better capture this
      population.

PMID- 24858201
TI  - Midtrimester isolated polyhydramnios in monochorionic diamniotic multiple
      gestations.
AB  - OBJECTIVE: To identify risk factors for development of twin-twin transfusion
      syndrome (TTTS) in monochorionic diamniotic multiple gestations complicated by
      midtrimester isolated polyhydramnios (iPoly). STUDY DESIGN: A retrospective study
      of patients referred for possible TTTS between 16 and 26 gestational weeks was
      performed. IPoly was defined as a maximum vertical pocket of >=8 cm in the iPoly
      twin's sac and >2 and <8 cm in the co-twin's sac on the consultative ultrasound.
      RESULTS: Of 628 consecutive patients referred for possible TTTS, 74 were
      diagnosed with iPoly. The majority of these patients (n = 52, 70.3%) were not
      subsequently diagnosed with TTTS, and of these, 40 were managed expectantly and
      12 had amnioreductions because of symptomatic iPoly; 30-day perinatal survival of
      at-least-one twin in the non-TTTS group was 93.0% (40/43). TTTS developed in the
      22 remaining patients, of which 63.6% were of advanced Quintero Stage. Nineteen
      underwent laser surgery; 30-day perinatal survival of at-least-one twin was 84.2%
      (16/19). In a multivariate logistic regression model, 2 characteristics were
      associated with the development of TTTS: (1) gestational age <20 weeks at the
      time of diagnosis of iPoly (odds ratio, 13.48; 95% confidence interval, 3.40
      53.48; P = .0002); and (2) intrauterine growth restriction of the co-twin (odds
      ratio, 7.28; 95% confidence interval, 1.72-30.88; P = .0071). CONCLUSION: Among
      referred patients with midtrimester iPoly, 29.7% subsequently developed TTTS.
      Early diagnosis (<20 weeks) and/or co-twin intrauterine growth restriction were
      significant risk factors for development of TTTS in these patients.

PMID- 24858202
TI  - Neonatal and early childhood outcomes following early vs later preterm premature
      rupture of membranes.
AB  - OBJECTIVE: Data regarding long-term outcomes of neonates reaching viability
      following early preterm premature rupture of membranes (PPROM; <25.0 weeks at
      rupture) are limited. We hypothesized that babies delivered after early PPROM
      would have increased rates of major childhood morbidity compared with those with
      later PPROM (>=25.0 weeks at rupture). STUDY DESIGN: This was a secondary
      analysis of a multicenter randomized controlled trial of magnesium sulfate vs
      placebo for cerebral palsy prevention. Women with singletons and PPROM of 15-32
      weeks were included. All women delivered at 24.0 weeks or longer. Those with
      PPROM less than 25.0 weeks (cases) were compared with women with PPROM at 25.0
      31.9 weeks (controls). Composite severe neonatal morbidity (sepsis, severe
      intraventricular hemorrhage, periventricular leukomalacia, severe necrotizing
      enterocolitis, bronchopulmonary dysplasia, and/or death) and composite severe
      childhood morbidity at age 2 years (moderate or severe cerebral palsy and/or
      Bayley II Infant and Toddler Development scores greater than 2 SD below the mean)
      were compared. RESULTS: A total of 1531 women (275 early PPROM cases) were
      included. Demographics were similar between the groups. Cases delivered earlier
      (26.6 vs 30.1 weeks, P < .001) and had a longer rupture-to-delivery interval
      (20.0 vs 10.4 days, P < .001). Case neonates had high rates of severe composite
      neonatal morbidity (75.6% vs 21.8%, P < .001). Children with early PPROM had
      higher composite severe childhood morbidity (51.6% vs 22.5%, P < .001). Early
      PPROM remained associated with composite severe childhood morbidity in
      multivariable models, even when controlling for delivery gestational age and
      other confounders. CONCLUSION: Early PPROM is associated with high rates of
      neonatal morbidity. Early childhood outcomes at age 2 years remain poor compared
      with those delivered after later PPROM.

PMID- 24858203
TI  - Sex-specific effects of maternal anthropometrics on body composition at birth.
AB  - OBJECTIVE: The purpose of this study was to assess whether maternal factors that
      are associated with fetal lean and fat mass differ between sexes. STUDY DESIGN:
      Secondary analysis of a prospective cohort that delivered by scheduled cesarean
      section from 2004-2013. Maternal blood was collected before surgery for metabolic
      parameters. Placental weight and neonatal anthropometrics were measured within 48
      hours. Anthropometric differences between sexes were assessed with the Student t
      test. Multiple stepwise regression analysis assessed the relationship between
      independent maternal variables and neonatal lean body mass (LBM), fat mass (FM),
      or percentage of fat as dependent variables in male and female infants combined
      and separately. RESULTS: We analyzed 360 women with normal glucose tolerance and
      a wide range of pregravid body mass index (16-64 kg/m(2)) and their offspring
      (male, 194; female, 166). Male infants had more FM (mean difference, 40 +/- 18 g;
      P = .03) and LBM (mean difference, 158 +/- 34 g; P < .0001) than female infants.
      Percentage of body fat and measured maternal variables did not differ between
      sexes. In both sexes, placental weight had the strongest correlation with both
      neonatal LBM and FM, which accounted for 20-39% of the variance. In male infants,
      maternal height, body mass index, and weight gain were significant predictors of
      both lean and fat mass. In female infants, plasma interleukin-6 and C-reactive
      protein, respectively, were associated independently with percentage of body fat
      and LBM. CONCLUSION: Our findings suggest that the body composition and
      inflammatory environment of the mother modulate the metabolic fitness of
      neonates, as predicted by fat and lean mass, in a sex-specific manner.

PMID- 24858204
TI  - Dynamics of interleukin-21 production during the clinical course of primary and
      secondary dengue virus infections.
AB  - Previous studies have revealed the clinical relevance of pro-inflammatory
      cytokine production during dengue virus (DENV) infections. In this study, we
      evaluated the production of interleukin-21 (IL-21), a key soluble mediator mainly
      produced by CD4+ T cells. The aim of this study was to investigate the role of IL
      21 production during the clinical course of primary and secondary DENV infections
      and the potential association of IL-21 serum levels with the disease
      pathogenesis. Blood samples from DENV-infected patients were collected on
      different days after the onset of symptoms. Patients were classified according to
      their phase of disease (acute vs. convalescent phases), the type of infection
      (primary vs. secondary), and the clinical severity of their disease (dengue fever
      (DF) vs. dengue hemorrhagic fever (DHF)). IL-21 levels were measured using a
      quantitative capture ELISA assay. The levels of IL-21 were significantly elevated
      in the disease group compared with the control group. IL-21 was detected in
      primary and secondary DENV infections, with a significantly higher concentration
      in the convalescent phase of primary infections. IL-21 levels were significantly
      higher in patients with secondary acute DHF infections when compared with those
      with secondary acute DF infection. There was a relationship between the elevated
      serum levels of IL-21 and the production of DENV-specific IgM and IgG antibodies.
      Taking together, our results show for the first time the involvement of IL-21
      during the clinical course of DENV infections. We speculate that IL-21 may play a
      protective role in the context of the convalescent phase of primary infections
      and the acute phase of secondary infections. 

PMID- 24858206
TI  - Sohlh2 inhibits ovarian cancer cell proliferation by upregulation of p21 and
      downregulation of cyclin D1.
AB  - Spermatogenesis and oogenesis basic helix-loop-helix (bHLH) transcription factor
      2 (Sohlh2) functions as a bhlh transcription factor to regulate mouse germ cell
      differentiation. Our previous data showed that Sohlh2 was highly expressed in
      human normal tissues, but low level of Sohlh2 was observed in many cancer cell
      lines, suggesting a possible role of Sohlh2 in tumorigenesis. In this study, we
      examined this possibility by using immunohistochemistry, MTT, 5-bromo-2
      deoxyuridine, clonogenic assay and tumor xenograft techniques. Our results showed
      that the expression of Sohlh2 was decreased in epithelial ovarian carcinoma (EOC)
      tissues compared with benign ovarian tumors and ovarian tumors with low malignant
      potential. Forced expression of Sohlh2 led to a significant reduction in cancer
      cell proliferation in vitro and tumorigenesis in nude mice. Conversely, silencing
      of Sohlh2 enhanced ovarian cancer cell proliferation. Furthermore, Sohlh2 had
      opposite effects on its two direct targets p21 and cyclin D1: overexpression of
      Sohlh2 upregulated p21 but downregulated cyclin D1 expression. p21 knockdown
      could reverse the effects of Sohlh2 overexpression on inhibiting cell
      proliferation, and cyclin D1 knockdown could reverse the effects of Sohlh2
      ablation on promoting cell proliferation. Thus, our data indicate that Sohlh2
      likely functions as a tumor suppressor in EOCs, which is achieved by inducing p21
      expression but repressing cyclin D1 expression. 

PMID- 24858207
TI  - Recent advances in the molecular diagnosis of inborn errors of metabolism.

PMID- 24858205
TI  - Elevated HERV-K mRNA expression in PBMC is associated with a prostate cancer
      diagnosis particularly in older men and smokers.
AB  - Aberrant expression of subgroup k human endogenous retroviruses (HERV-K) has been
      observed in prostate cancer. This subgroup is unique because it encodes sequences
      in the human genome containing open reading frames for near intact retroviruses.
      We hypothesized that HERV-K reactivation could serve as a non-invasive early
      disease detection marker for prostate cancer. We evaluated HERV-K gag messenger
      RNA (mRNA) expression in blood samples of African-American and European-American
      men using a case-control design via quantitative real-time PCR. Additionally, we
      examined HERV-K envelope protein expression in prostate tumors by
      immunohistochemistry. HERV-K envelope protein was commonly upregulated in
      prostate tumors, but more so in tumors of African-American than European-American
      patients (61% versus 40%, P < 0.01). Examining HERV-K gag expression in
      peripheral blood mononuclear cells (PBMC) from 294 cases and 135 healthy men, we
      found that the abundance of HERV-K gag message was significantly higher in cases
      than controls and was associated with increased plasma interferon-gamma. Men with
      gag expression in the highest quartile had >12-fold increased odds {odds ratio =
      12.87 [95% confidence interval 6.3-26.25]} of being diagnosed with prostate
      cancer than those in the lowest quartile. Moreover, our results showed that HERV
      K expression may perform better as a disease biomarker in older than younger men
      (whereas the sensitivity of prostate-specific antigen (PSA) testing decreases
      with age) and in men with a smoking history compared with never smokers.
      Combining non-invasive HERV-K testing with PSA testing may improve the efficacy
      of prostate cancer detection specifically among older men and smokers who tend to
      develop a more aggressive disease. 

PMID- 24858208
TI  - Closing the gaps in pediatric reference intervals: an update on the CALIPER
      project.

PMID- 24858209
TI  - The role of the IFCC in supporting e-learning through the Internet.

PMID- 24858210
TI  - Measurement of GFR for children and an LC-MS/MS method for nonradioactive
      iothalamate.

PMID- 24858211
TI  - Pediatric reference intervals - the Swedish experience.

PMID- 24858212
TI  - A facile route to modify ferrous phosphate and its use as an iron-containing
      resource for LiFePO4 via a polyol process.
AB  - This study introduces an economical and environmentally friendly way of
      synthesizing LiFePO4/C to be used as cathode material in lithium ion batteries
      via two processes: (1) the synthesis of LiFePO4/C cathode material using a low
      cost divalent precursor ferrous phosphate, Fe3 (PO4)2.8H2O, as iron source in a
      polyol process and (2) the modification of the morphology of this precursor by
      varying the reaction time in a coprecipitation process. The study examines the
      effects of different structures and morphologies of the precursor on the
      structure and electrochemical performance of the as-synthesized LiFePO4/C. The
      LiFePO4/C shows an excellent rate capability and cycle performance, with initial
      discharge capacities of 153, 128, and 106 mA h g(-1) at 1 C, 5 C, and 10 C. The
      capacity retention is respectively 98.7%, 98.2%, and 98.7%, after 10 cycles at
      the corresponding rates. The capacity retention remains at 97% even after 300
      cycles at the rate of 10 C. The outstanding electrochemical performance can be
      attributed to the improved rate of Li(+) diffusion and the excellent
      crystallinity of synthesized LiFePO4/C powders through the modified precursor.
      Therefore, this is an economical and environmentally friendly way of synthesizing
      LiFePO4/C to be used as cathode material in lithium ion batteries. 

PMID- 24858213
TI  - A neuropathology-based approach to epilepsy surgery in brain tumors and proposal
      for a new terminology use for long-term epilepsy-associated brain tumors.
AB  - Every fourth patient submitted to epilepsy surgery suffers from a brain tumor.
      Microscopically, these neoplasms present with a wide-ranging spectrum of glial or
      glio-neuronal tumor subtypes. Gangliogliomas (GG) and dysembryoplastic
      neuroepithelial tumors (DNTs) are the most frequently recognized entities
      accounting for 65 % of 1,551 tumors collected at the European Epilepsy Brain Bank
      (n = 5,842 epilepsy surgery samples). These tumors often present with early
      seizure onset at a mean age of 16.5 years, with 77 % of neoplasms affecting the
      temporal lobe. Relapse and malignant progression are rare events in this
      particular group of brain tumors. Surgical resection should be regarded,
      therefore, also as important treatment strategy to prevent epilepsy progression
      as well as seizure- and medication-related comorbidities. The characteristic
      clinical presentation and broad histopathological spectrum of these highly
      epileptogenic brain tumors will herein be classified as "long-term epilepsy
      associated tumors-LEATs". LEATs differ from most other brain tumors by early
      onset of spontaneous seizures, and conceptually are regarded as developmental
      tumors to explain their pleomorphic microscopic appearance and frequent
      association with Focal Cortical Dysplasia Type IIIb. However, the broad
      neuropathologic spectrum and lack of reliable histopathological signatures make
      these tumors difficult to classify using the WHO system of brain tumors. As
      another consequence from poor agreement in published LEAT series, molecular
      diagnostic data remain ambiguous. Availability of surgical tissue specimens from
      patients which have been well characterized during their presurgical evaluation
      should open the possibility to systematically address the origin and
      epileptogenicity of LEATs, and will be further discussed herein. As a conclusion,
      the authors propose a novel A-B-C terminology of epileptogenic brain tumors
      ("epileptomas") which hopefully promote the discussion between neuropathologists,
      neurooncologists and epileptologists. It must be our future mission to achieve
      international consensus for the clinico-pathological classification of LEATs that
      would also involve World Health Organization (WHO) and the International League
      against Epilepsy (ILAE).

PMID- 24858214
TI  - Inhibitory effect of nitrite on coagulation processes demonstrated by
      thrombelastography.
AB  - Nitric oxide (NO) can be generated by two-step reduction pathway in which nitrate
      is converted first into nitrite and then into NO via several mechanisms, as well
      as from arginine by endogenous nitric oxide synthase (NOS). We have recently
      shown that nitrite ions in the presence of erythrocytes inhibit platelet
      aggregation and activation, as measured by aggregometry and flow cytometric
      analysis of P-selectin, through its reduction to NO under partially deoxygenated
      conditions. In the current study, we investigated how nitrite may affect overall
      clotting processes via modulating platelet function using thrombelastography
      (TEG). We measured three major TEG parameters, reaction time (R, time to initial
      fibrin formation), alpha angle (velocity of clot growth) and maximum amplitude
      (MA, maximum clot strength) using blood from healthy volunteers. An NO donor
      (DEANONOate) showed inhibitory effects on all TEG parameters in platelet rich
      plasma (PRP) and whole blood, resulting in delayed R, decreased angle, and
      reduced MA in a dose dependent manner. Nitrite ions also exhibited inhibitory
      effects in whole blood at 20% hematocrit, and this was greatly enhanced under
      hypoxic conditions, being demonstrable at 0.1 MUM concentration. Neither compound
      changed any TEG parameters in plasma. Our results suggest that nitrite affects
      overall blood clotting and that TEG may be used to follow this process. Further
      the physiological effects of factors which determine NO bioavailability, such as
      endogenous levels of blood and tissue nitrite, may be useful as biomarkers for
      predicting hemostatic potential.

PMID- 24858215
TI  - Hypoxic potentiation of nitrite effects in human vessels and platelets.
AB  - Previous studies in non-human blood vessels and in platelets have demonstrated
      that under hypoxic conditions release of NO from nitrite (NO2(-)) is potentiated
      by deoxyhaemoglobin. In the current study, we characterized hypoxic potentiation
      of NO2(-) effects in human vasculature and platelets in vitro, addressing
      underlying mechanisms. The vasodilator efficacy of NO2(-), in comparison with
      glyceryl trinitrate (GTN), was evaluated in vitro, using segments of human
      saphenous vein. Under hypoxic conditions, there was a leftward shift of the NO2(
      ) concentration-response curve (EC50: 22 MUM in hyperoxia vs 3.5 MUM in hypoxia;
      p<0.01), but no significant potentiation of GTN effect. In the presence of red
      blood cells, hypoxic potentiation of NO2(-) vasodilator effect was accentuated.
      In whole blood samples and platelet-rich plasma (PRP) we assessed inhibition of
      platelet aggregation by NO2(-) (1mM), in comparison with that of sodium
      nitroprusside (SNP, 10 MUM). In individual subjects (n=37), there was a strong
      correlation (r=0.75, p<0.0001) between anti-aggregatory effects of NO2(-) and SNP
      in whole blood, signifying that resultant sGC activation underlies biological
      effect and responses to NO2(-) are diminished in the presence of NO resistance.
      In PRP, the effects of NO2(-) were less pronounced than in whole blood
      (p=0.0001), suggesting an important role of Hb (within RBCs) in the bioconversion
      of NO2(-) to NO. Inhibition of platelet aggregation by NO2(-) was almost 3-fold
      greater in venous than in arterial blood (p<0.0001), and deoxyHb concentration
      directly correlated (r=0.69, p=0.013) with anti-aggregatory response. Incremental
      hypoxia applied to venous blood samples (in hypoxic chamber) caused a progressive
      increase in both deoxyHb level and anti-aggregatory effect of NO2(-). When
      subjects inhaled a 12% O2 mixture for 20 min, there was a 3-fold rise in blood
      deoxyHb fraction (p<0.01). In PRP, response to NO2(-) also increased under
      hypoxia, and was further enhanced (p<0.01) by deoxyHb. Furthermore, deoxyHb
      exerted significant anti-aggregatory effects even in the absence of added NO2(-),
      suggesting a role for endogenous NO2(-). The results of this work provide further
      mechanistic insights into hypoxic potentiation of vasodilator and anti
      aggregatory actions of NO2(-). In human saphenous veins and blood, the balance of
      evidence suggests differential rates of NO release from NO2(-) (largely modulated
      by deoxyHb) as the fundamental mechanism.

PMID- 24858216
TI  - Monitoring of event-based mobilization of hydrophobic pollutants in rivers:
      calibration of turbidity as a proxy for particle facilitated transport in field
      and laboratory.
AB  - Transport of many pollutants in rivers is coupled to mobilization of suspended
      particles which typically occurs during floods. Since the amount of total
      suspended solids (TSS) in rivers can be monitored by turbidity measurements this
      may be used as a proxy for the total concentration of particle associated
      pollutants such as PAHs, PCBs, etc. and several heavy metals. Online turbidity
      measurements (e.g. by optical backscattering sensors) would then also allow for
      an assessment of particle and pollutant flux dynamics if once calibrated against
      TSS and total pollutant concentrations for a given catchment. In this study,
      distinct flood and thus turbidity events were sampled at high temporal resolution
      in three contrasting sub-catchments of the River Neckar in Southwest Germany
      (Ammer, Goldersbach, Steinlach) as well as in the River Neckar itself and
      investigated for the total amount of PAHs and TSS in water; turbidity (NTU) and
      grain size distributions of suspended solids were determined as well. Laboratory
      experiments were performed with natural river bed sediments from different
      locations (Ammer) to investigate PAH concentrations, TSS and turbidity during
      sedimentation of suspended particles under controlled conditions (yielding
      smaller and smaller suspended particles and TSS with time). Laboratory and field
      results agreed very well and showed that turbidity and TSS were linearly
      correlated over an extended turbidity range up to 2000 NTU for the field samples
      and up to 8000 NTU in lab experiments. This also holds for total PAH
      concentrations which can be reasonably well predicted based on turbidity
      measurements and TSS vs. PAHs relationships - even for high turbidity values
      observed during flood events (>2000 NTU). Total PAH concentrations on suspended
      solids were independent of grain size of suspended particles. This implies that
      for the rivers investigated the sorption capacity of particles did not change
      significantly during the observed events.

PMID- 24858217
TI  - Source contributions of PAHs and toxicity in reed wetland soils of Liaohe estuary
      using a CMB-TEQ method.
AB  - 16 US EPA priority PAHs were analyzed in surface soils collected from reed
      wetland of Liaohe estuary. Total concentrations of the sixteen PAHs ranged from
      235 ng g(-1) to 374 ng g(-1), while the total concentrations of seven
      carcinogenic PAHs (cPAHs) varied from 82.6 ng g(-1) to 109 ng g(-1). Toxicity of
      PAHs was assessed using toxic equivalent quantity (TEQ). The BaP and DBahA were
      the major contributors to TEQBaP, although IND showed the highest concentration
      level. Quantitative source apportionment of PAHs and toxicity (i.e. TEQBaP) were
      performed, using the CMB-TEQ (chemical mass balance model and TEQ) method.
      Results showed that, the vehicular sources (gasoline and diesel engine emissions)
      yielded a higher contribution to TEQBaP (95.7%) than that to PAHs (57.1%), while
      petrogenic source and biomass burning, two important contributors for total PAHs
      (21.6% and 21.3%, respectively), contributed a little to TEQBaP (3.6% and 0.7%,
      respectively).

PMID- 24858218
TI  - Biomonitoring of traffic-related nitrogen pollution using Letharia vulpina (L.)
      Hue in the Sierra Nevada, California.
AB  - To assess the impact of vehicular emissions on a mixed conifer forest, we
      measured the contents of the trace elements, N, C, and their respective natural
      isotopes (delta(15)N and delta(13)C), in the epiphytic lichen, L. vulpina. The
      samples were collected along transects perpendicular to Interstate 80 (I-80) and
      along a more remote, secondary forest road (R07). Distance to the road verge,
      trunk cover, and stand basal area were also recorded. Percent N ranged from 1.10%
      to 2.00% near I-80 and from 0.78% to 1.13% along R07. Concentrations of N, (15)N,
      Na, As, Pb, and Zn were enhanced in lichen samples near I-80 and were negatively
      correlated with distance from the road. Trunk cover values differed between roads
      (p<0.001) and were negatively correlated with %N (r(2)=0.74; p<0.001). The
      results indicate that vehicular N emissions are significant enough to alter the
      surrounding ecosystem, modifying the presence of a sensitive component such as L.
      vulpina, and suggest that a clean-site threshold of 1.0%N may be too high as an
      indicator of critical N load exceedance. The study also underscored the potential
      role of wolf lichen in a large-scale assessment of N deposition and source
      identification.

PMID- 24858219
TI  - Tracing nitrate pollution sources and transformation in surface- and ground
      waters using environmental isotopes.
AB  - Water pollution in the form of nitrate nitrogen (NO3(-)-N) contamination is a
      major concern in most agricultural areas in the world. Concentrations and
      nitrogen and oxygen isotopic compositions of nitrate, as well as oxygen and
      deuterium isotopic compositions of surface and groundwater from a typical
      irrigated region in the North China Plain (NCP) collected from May to October in
      2012 were analyzed to examine the major nitrate sources and transformations.
      Concentrations of NO3(-)-N ranged from 0.2 to 29.6 mg/L (mean of 11.2 mg/L) in
      surface water, and from 0.1 to 19.4 mg/L (mean of 2.8 mg/L) in groundwater.
      Approximately 46.7% of the surface water samples and 10% of the groundwater
      samples exceeded the World Health Organization (WHO) drinking water standard for
      NO3(-)-N. Surface water samples that exceeded the standard were collected mainly
      in the dry season (May and October), while groundwater samples that exceeded the
      standard were collected in the wet season (June). Overall, the highest nitrate
      levels were observed in surface water in May and in groundwater in June,
      indicating that fertilizer application, precipitation, and irrigation strongly
      influence the NO3(-)-N concentrations. Analyses of isotopic compositions suggest
      that the main sources of nitrate are nitrification of fertilizer and sewage in
      surface water, in contrast, mineralization of soil organic N and sewage is the
      groundwater sources during the dry season. When fertilizers are applied, nitrate
      will be transported by precipitation through the soil layers to the groundwater
      in the wet season (June). Denitrification only occurred in surface water in the
      wet season. Attempts should be made to minimize overuse of nitrogen fertilizers
      and to improve nitrogen use efficiency in irrigated agricultural regions.

PMID- 24858220
TI  - Photosonochemical degradation of butyl-paraben: optimization, toxicity and
      kinetic studies.
AB  - The objective of the present work is to evaluate the potential of a
      photosonolysis process for the degradation of butyl-paraben (BPB). After 120 min
      of treatment time, high removal of BPB was achieved by the photosonolysis (US/UV)
      process (88.0+/-0.65%) compared to the photochemical (UV) and the conventional
      ultrasonication (US) processes. Several factors such as calorimetric power,
      treatment time, pH and initial concentration of BPB were investigated. Using a
      2(4) factorial matrix, the treatment time and the calorimetric power are the main
      parameters influencing the degradation rate of BPB. Subsequently, a central
      composite design methodology has been investigated to determine the optimal
      experimental parameters for BPB degradation. The US/UV process applied under
      optimal operating conditions (at a calorimetric power of 40 W during 120 min and
      under pH7) is able to oxidize around 99.2+/-1.4% of BPB and to record 43.3% of
      mineralization. During the US/UV process, BPB was mainly transformed into 1
      hydroxy BPB, dihydroxy BPB, hydroquinone and 4-hydroxybenzoic acid. Microtox
      biotests (Vibrio fisheri) showed that the treated effluent was not toxic. The
      pseudo-first order kinetic model (k=0.0367 min(-1)) described very well the
      oxidation of BPB.

PMID- 24858221
TI  - Analysis of organic contaminant desorption kinetic data for sediments and soils:
      implications for the Tenax extraction time for the determination of bioavailable
      concentrations.
AB  - Solid-phase extractions with adsorbents like Tenax have been widely used to
      assess bioaccessible or bioavailable concentrations and non-extractable residues
      (NER) of organic contaminants in soils or sediments. This paper presents an
      analysis of literature rate constants and fractions for rapid, slow and very slow
      contaminant desorption from soils and sediments. Contaminant fractions desorbed
      from sediment to Tenax in 6 or 24h were evaluated as to their adequacy as a proxy
      for rapidly desorbing fractions, which have been shown to correlate with
      bioavailable concentrations. Desorption rate constants appear to decrease with
      increasing contaminant n-octanol-water partition coefficient. The ratio of the
      fraction of contaminant desorbed from sediment to Tenax in 6h and the rapidly
      desorbing fraction appeared to slightly decrease on increasing contaminant
      hydrophobicity. This was not the case for the extraction for 24h. Rapidly
      desorbing fractions or bioavailable fractions can be estimated, within a factor
      of 1.4, by multiplying the fraction desorbed in 24h by a factor of 0.7. 

PMID- 24858222
TI  - Biogenic volatile organic compound (BVOC) emissions from forested areas in
      Turkey: determination of specific emission rates for thirty-one tree species.
AB  - Normalized biogenic volatile organic compound (BVOC) emission rates for thirty
      one tree species that cover the 98% of national forested areas in Turkey were
      determined. Field samplings were performed at fourteen different forested areas
      in Turkey using a specific dynamic enclosure system. The selected branches of
      tree species were enclosed in a chamber consisted of a transparent Nalofan bag.
      The air-flows were sampled from both inlet and outlet of the chamber by Tenax
      filled sorbent tubes during photosynthesis of trees under the presence of
      sunlight. Several environmental parameters (temperature, humidity,
      photosynthetically active radiation-PAR, and CO2) were continuously monitored
      inside and outside the enclosure chamber during the samplings. Collected samples
      were analyzed using a gas chromatography mass spectrometry (GC/MS) system
      equipped with a thermal desorber (TD). Sixty five BVOCs classified in five major
      groups (isoprene, monoterpenes, sesquiterpenes, oxygenated sesquiterpenes, and
      other oxygenated compounds) were analyzed. Emission rates were determined by
      normalization to standard conditions (1000 MUmol/m(2)s PAR and 30  degrees C
      temperature for isoprene and 30  degrees C temperature for the remaining
      compounds). In agreement with the literature, isoprene was mostly emitted by
      broad-leaved trees while coniferous species mainly emitted monoterpenes. Several
      tree species such as Sweet Chestnut, Silver Lime, and European Alder had higher
      monoterpene emissions although they are broad-leaved species. High isoprene
      emissions were also observed for a few coniferous species such as Nordmann Fir
      and Oriental Spruce. The highest normalized total BVOC emission rate of 27.1
      MUg/gh was observed for Oriental Plane while South European Flowering Ash was the
      weakest BVOC emitter with a total normalized emission rate of 0.031 MUg/gh.
      Monoterpene emissions of broad-leaved species mainly consisted of sabinene,
      limonene and trans-beta-ocimene, while alpha-pinene, beta-pinene and beta-myrcene
      were generally emitted by coniferous species. Oxygenated compounds were the third
      most prominent BVOC group and sesquiterpenes had slightly lower contributions.

PMID- 24858223
TI  - Influence of household cleaning practices on the magnitude and variability of
      urinary monochlorinated bisphenol A.
AB  - Low-dose health effects of BPA have not been adequately explored in the presence
      of BPA metabolites of chlorinated structure that may exert larger estrogenic
      effects than those of their parent compound. We hypothesized that chlorine
      containing cleaning products used in household cleaning activities could modify
      the magnitude of total urinary BPA concentration measurements via the production
      of chlorinated BPA (ClBPA) derivatives. Our objective was to investigate the
      influence of typical household cleaning activities (dishwashing, toilet cleaning,
      mopping, laundry, etc.) on the magnitude and variability of urinary total BPA and
      mono-ClBPA levels in the general adult population. A cross-sectional study
      (n=224) included an adult (>=18 years) pool of participants from the general
      population of Nicosia, Cyprus. First morning urine voids were collected, and
      administered questionnaires included items about household cleaning habits,
      demographics, drinking water consumption rates and water source/usage patterns.
      Urinary concentrations of total BPA (range: 0.2-82 MUg L(-1)), mono-ClBPA (16-340
      ng L(-1)), and total trihalomethanes (0.1-5.0 MUg L(-1)) were measured using gas
      chromatography coupled with triple quadrupole mass spectrometry and large volume
      injection. Linear multiple regression analysis revealed that dishwashing along
      with age and gender (females) were able to predict urinary mono-ClBPA levels (ng
      g(-1)), even after adjusting for covariates; this was not the case for urinary
      total BPA levels (ng g(-1)). Significant (p<0.001) association was observed
      between urinary mono-ClBPA and THM levels, underlying the important role of
      disinfectant (chlorine) in promoting formation of both ClBPA and THM. Urinary
      mono-ClBPA levels were measured for the first time using an appreciable sample
      size, highlighting the co-occurring patterns of both total BPA and mono-ClBPA.
      Epidemiological studies and probabilistic BPA risk assessment exercises should
      consider assessing daily intake estimates for chlorinated BPA compounds, as well.

PMID- 24858224
TI  - Monitoring land use/land cover transformations from 1945 to 2007 in two peri
      urban mountainous areas of Athens metropolitan area, Greece.
AB  - The aims of this study were to map and analyze land use/land cover transitions
      and landscape changes in the Parnitha and Penteli mountains, which surround the
      Athens metropolitan area of Attica, Greece over a period of 62 years. In order to
      quantify the changes between land categories through time, we computed the
      transition matrices for three distinct periods (1945-1960, 1960-1996, and 1996
      2007), on the basis of available aerial photographs used to create multi-temporal
      maps. We identified systematic and stationary transitions with multi-level
      intensity analysis. Forest areas in Parnitha remained the dominant class of land
      cover throughout the 62 years studied, while transitional woodlands and
      shrublands were the main classes involved in LULC transitions. Conversely, in
      Penteli, transitional woodlands, along with shrublands, dominated the study site.
      The annual rate of change was faster in the first and third time intervals,
      compared to the second (1960-1996) time interval, in both study areas. The
      category level analysis results indicated that in both sites annual crops avoided
      to gain while discontinuous urban fabric avoided to lose areas. At the transition
      level of analysis, similarities as well as distinct differences existed between
      the two areas. In both sites the gaining pattern of permanent crops with respect
      to annual crops and the gain of forest with respect to transitional
      woodland/shrublands were stationary across the three time intervals. Overall, we
      identified more systematic transitions and stationary processes in Penteli. We
      discussed these LULC changes and associated them with human interference
      (activity) and other major socio-economic developments that were simultaneously
      occurring in the area. The different patterns of change of the areas, despite
      their geographical proximity, throughout the period of analysis imply that site
      specific studies are needed in order to comprehensively assess the driving forces
      and develop models of landscape transformation in Mediterranean areas.

PMID- 24858225
TI  - A one-year follow-up analysis of antidepressants in Portuguese wastewaters:
      occurrence and fate, seasonal influence, and risk assessment.
AB  - The occurrence, fate, seasonal influence and environmental risk assessment of
      four selective serotonin re-uptake inhibitors (SSRIs) antidepressants,
      citalopram, fluoxetine, paroxetine and sertraline, were studied in 15 different
      wastewater treatment plants (WWTPs) across Portugal. Influent and effluent
      samples from four sampling campaigns, in 2013, were extracted through Oasis HLB
      cartridges, and quantified through liquid chromatography with tandem mass
      spectrometry (LC-MSn).Results showed that citalopram was the SSRI most frequently
      found, both in influents and in effluents, with mean mass loads ranging between
      14.56 and 9.51 mg/day/1000 inhabitants, respectively. Fluoxetine and sertraline
      were only detected in influent samples, in lower mean mass loads (14.60 and 1.36
      mg/day/1000 inhab., respectively), whereas paroxetine was found in influent and
      effluent samples (12.61 and 18.90 mg/day/1000 inhab., respectively). WWTPs were
      not capable of completely removing these pharmaceuticals; nonetheless, the mean
      removal efficiency was 82.24%. Removal efficiency was lower in winter (74.21%),
      summer (72.02%), and autumn (81.19%), when compared to spring (100%). Our results
      translate the variations in SSRI prescription and use between the five Portuguese
      regions in study. Influent contaminated samples were found in WWTPs from Lisbon,
      Alentejo, Center and North (28.25, 19.01, 16.55 and 6.98 mg/day/1000 inhab.,
      respectively). In the Algarve region no contaminated samples were found. A
      seasonal pattern in the presence of SSRIs in influent wastewaters was observed.
      The SSRIs mass loads in influent wastewaters were higher in autumn, followed by
      spring, winter, and summer. Finally, the potential ecotoxicological risk posed by
      SSRIs to different trophic levels of aquatic organisms, exposed to the effluent
      wastewaters studied was evaluated by means of risk quotients (RQ). Citalopram and
      paroxetine, the only SSRIs found in these samples, presented RQ lower than 1.
      According to the results, algae appeared to be the most sensitive followed by
      fish and daphnids.

PMID- 24858226
TI  - Occurrence and removal of estrogens in Brazilian wastewater treatment plants.
AB  - This paper evaluated the occurrence and removal efficiency of four estrogenic
      hormones in five biological wastewater treatment plants (WWTPs), located in the
      State of Ceara, Brazil. The five WWTPs comprised: two systems consisted of one
      facultative pond followed by two maturation ponds, one facultative pond, one
      activated sludge (AS) system followed by a chlorination step, and one upflow
      anaerobic sludge blanket (UASB) reactor followed by a chlorination step. Estrogen
      occurrence showed a wide variation among the analyzed influent and effluent
      samples. Estrone (E1) showed the highest occurrence in the influent (76%),
      whereas both 17beta-estradiol (E2) and 17alpha-ethynylestradiol (EE2) presented a
      52% occurrence, and the compound 17beta-estradiol 17-acetate (E2-17A), a 32% one.
      The occurrence in the effluent samples was 48% for E1, 28% for E2, 12% for E2
      17A, and 40% for EE2. The highest concentrations of E1 and EE2 hormones in the
      influent were 3050 and 3180 ng L(-1), respectively, whereas E2 and E2-17A had
      maximum concentrations of 776 and 2300 ng L(-1), respectively. The lowest
      efficiencies for the removal of estrogenic hormones were found in WWTP consisted
      of waste stabilization ponds, ranging from 54 to 79.9%. The high-rate systems (AS
      and UASB), which have chlorination as post-treatment, presented removal
      efficiencies of approximately 95%.

PMID- 24858227
TI  - Pharmaceuticals and personal care products in chicken meat and other food animal
      products: a market-basket pilot study.
AB  - Pharmaceutical drugs are extensively used in industrial food animal production.
      We examined whether residues of veterinary antibiotics and other pharmaceuticals
      and personal care products (PPCPs) were detectable in a small market-basket
      sample of retail chicken (n=39), ground beef (n=3) and milk (n=3) samples. High
      performance liquid chromatography and tandem mass spectrometry were used to
      assess the concentration of 59 PPCPs and their residues in animal products. All
      samples of ground beef, milk, and 14 chickens were analyzed individually, while
      an additional 25 chicken samples were pooled and analyzed in groups of five. The
      majority of PPCPs were not detected in meat and milk samples. Caffeine was
      detected in two of three milk samples (0.4 ng/mL, 2.0 ng/mL) and in 10 of 19
      individual and pooled chicken samples (median: 18.6 ng/g, range: 6.1-28.8 ng/g).
      Acetaminophen was detected in three of three milk samples (median: 1.5 ng/mL,
      range: 1.4-2.1 ng/mL). Antibiotics in the tetracycline class were detected in two
      of three milk samples (median: 1.0 ng/mL, range: 0.1-2.0 ng/mL) and did not
      exceed regulatory residue tolerances of 300 ng/mL. There are no regulatory
      residue tolerances for caffeine or acetaminophen in animal products. The
      acetaminophen detections in milk, however, raise questions about extra-label and
      unapproved use of pharmaceutical drugs in food animal production, as this drug is
      not approved for use in lactating dairy cattle or any other type of food animal
      production. Additional studies are needed to confirm our finding of PPCPs in meat
      and dairy products.

PMID- 24858228
TI  - Examining the influence of urban definition when assessing relative safety of
      drinking-water in Nigeria.
AB  - Reducing inequalities is a priority from a human rights perspective and in water
      and public health initiatives. There are periodic calls for differential national
      and global standards for rural and urban areas, often justified by the suggestion
      that, for a given water source type, safety is worse in urban areas. For
      instance, initially proposed post-2015 water targets included classifying urban
      but not rural protected dug wells as unimproved. The objectives of this study
      were to: (i) examine the influence of urban extent definition on water safety in
      Nigeria, (ii) compare the frequency of thermotolerant coliform (TTC)
      contamination and prevalence of sanitary risks between rural and urban water
      sources of a given type and (iii) investigate differences in exposure to
      contaminated drinking-water in rural and urban areas. We use spatially referenced
      data from a Nigerian national randomized sample survey of five improved water
      source types to assess the extent of any disparities in urban-rural safety. We
      combined the survey data on TTC and sanitary risk with map layers depicting urban
      versus rural areas according to eight urban definitions. When examining water
      safety separately for each improved source type, we found no significant urban
      rural differences in TTC contamination and sanitary risk for groundwater sources
      (boreholes and protected dug wells) and inconclusive findings for piped water and
      stored water. However, when improved and unimproved source types were combined,
      TTC contamination was 1.6 to 2.3 times more likely in rural compared to urban
      water sources depending on the urban definition. Our results suggest that
      different targets for urban and rural water safety are not justified and that
      rural dwellers are more exposed to unsafe water than urban dwellers.
      Additionally, urban-rural analyses should assess multiple definitions or
      indicators of urban to assess robustness of findings and to characterize a
      gradient that disaggregates the urban-rural dichotomy. 

PMID- 24858229
TI  - Pathways of human exposure to cobalt in Katanga, a mining area of the D.R. Congo.
AB  - Human exposure biomonitoring in the African Copperbelt (Katanga, southern D.R.
      Congo) revealed elevated cobalt (Co) exposure in the general population. This
      study was designed to identify the Co exposure routes for the non-occupationally
      exposed population in that area. The concentration of Co was measured in
      environmental and urine samples collected in urban and rural communities close to
      metal mining and/or refining plants, villages near a lake receiving effluents
      from metal refining plants, and control rural areas without industrial pollution.
      Drinking water, uncooked food items (maize flour, washed vegetables, fish and
      meat), indoor and outdoor dust samples were collected at each location. A food
      questionnaire was used to estimate dietary Co intake for adults and children.
      Geometric mean urine-Co (U-Co) concentrations were 4.5-fold (adults) and 6.6-fold
      (children) higher in the polluted than in the control area, with U-Co values
      being intermediate in the lakeside area. Average Co concentrations in
      environmental samples differed 6-40-fold between these areas. U-Co was positively
      correlated with most environmental Co concentrations, the highest correlations
      being found with Co in drinking water, vegetables and fruit. Estimated average
      total Co intake for adults was 63 (+/-42) MUg/day in the control area, 94 (+/-55)
      MUg/day in the lakeside villages and 570 (+/-100) MUg Co/day in the polluted
      areas. U-Co was significantly related to modelled Co intake (R(2)=0.48, adults
      and R(2)=0.47, children; log-log relationship). Consumption of legumes, i.e.
      sweet potato leaves (polluted) and cereals+fish (lakeside) was the largest
      contributor to Co intake in adults, whereas dust ingestion appeared to contribute
      substantially in children in the polluted area. In conclusion, dietary Co is the
      main source of Co exposure in the polluted area and Co is efficiently transferred
      from soil and water in the human food chain.

PMID- 24858230
TI  - The estrogen receptor signaling pathway activated by phthalates is linked with
      transforming growth factor-beta in the progression of LNCaP prostate cancer
      models.
AB  - The distinct roles of estrogen receptors (ERs) related with androgen receptors
      (ARs) have been proposed in prostate cancer, while the involvement of
      transforming growth factor-beta (TGF-beta) has been reported in the progression
      of prostate cancer. In this study, we examined whether the TGF-beta signaling
      pathway is associated with ER signaling in LNCaP prostate cancer cells, which
      express ERalpha, ERbeta and ARs. We determined whether the exposure to phthalates
      may induce prostate cancer progression by affecting molecular crosstalk between
      ER and TGF-beta signaling pathways. Cell viability was measured in LNCaP cells by
      MTT assay following treatment with di-n-buthyl phthalate (DBP). RT-PCR and
      immunoblot assay were performed to examine the expression levels of cell cycle
      related genes and the TGF-beta signaling cascade. A mouse xenograft model of
      prostate cancer was generated, and immunohistochemical and BrdU assay were
      carried out to determine the effect of DBP in this mouse model. DBP, a type of
      phthalate, was shown to promote LNCaP cell proliferation by upregulating the gene
      expression of c-myc and cyclin D1 and by downregulating the expression of p21.
      DBP significantly reduced the protein expression of p-smad similarly to E2. These
      regulations caused by DBP were reversed by ICI 182,780, an ER antagonist,
      indicating that DBP may affect crosstalk between TGF-beta and ER signals. In an
      in vivo mouse model, tumor volume of mice exposed to DBP was increased. Number of
      cells in S phase of cell cycle was increased by DBP, while expression of p21
      protein was reduced in the tissues of DBP-treated mice. These results indicate
      that DBP may induce the growth of LNCaP prostate cancer by acting on the
      crosstalk between TGF-beta and ER signaling pathways.

PMID- 24858231
TI  - Dezocine pretreatment prevents myoclonus induced by etomidate: a randomized,
      double-blinded controlled trial.
AB  - The aim of this randomized, double-blind, placebo-controlled clinical trial was
      to evaluate the effects of dezocine on the incidence and severity of myoclonus
      induced by etomidate. Patients (108) were randomly assigned to one of two groups
      to receive either 0.1 mg kg(-1) of dezocine (n = 54; Group D) or saline (n = 54;
      Group S) intravenously 1 min before 0.3 mg kg(-1) etomidate was given. The
      occurrence and severity (observational score of 0-3) of myoclonus was assessed
      for 2 min after administration of etomidate. The incidence and the intensity of
      myoclonus were significantly lower in Group D (0 %) than in Group S (75.9 %) (P <
      0.01), and all patients showed stable cardiovascular profiles. The results
      suggest that infusion of 0.1 mg kg(-1) dezocine 1 min before etomidate
      administration is effective for suppressing myoclonus induced by etomidate during
      induction of general anesthesia without significant side-effects.

PMID- 24858232
TI  - Effect of hexavalent chromium on histone biotinylation in human bronchial
      epithelial cells.
AB  - Chromium is a potent human mutagen and carcinogen. The capability of chromium to
      cause cancers has been known for more than a century, and numerous
      epidemiological studies have been performed to determine its carcinogenicity. In
      the post-genome era, cancer has been found to relate to epigenetic mutations.
      However, very few researches have focused on hexavalent chromium (Cr(VI))-induced
      epigenetic alterations. The present study was designed to investigate whether
      Cr(VI) would affect the level of a newfound epigenetic modification: histone
      biotinylation. Histone acetylation and histone biotinylation were studied in
      detail using human bronchial epithelial (16HBE) cells as an in vitro model after
      Cr(VI) treatment. Our study showed that Cr(VI) treatment decreased histone
      acetylation level in 16HBE cells. In addition, low doses of Cr(VI) (<=0.6MUM)
      elevated the level of histone biotinylation. Furthermore, immunoblot analysis of
      biotinidase (BTD), a major protein which maintains homeostasis of histone
      biotinylation, showed that the distribution of BTD became less even and more
      concentrated at the nuclear periphery in cells exposed to Cr(VI). Moreover,
      Cr(VI)-induced histone deacetylation may take part in the regulation of histone
      biotinylation. Together, our study provides new insight into the mechanisms of
      Cr(VI)-induced epigenetic regulation that may contribute to the chemoprevention
      of Cr(VI)-induced cancers and may have important implications for epigenetic
      therapy. 

PMID- 24858233
TI  - "Low-intensity laser therapy effect on the recovery of traumatic spinal cord
      injury".
AB  - Scientific advances have been made to optimize the healing process in spinal cord
      injury. Studies have been developed to obtain effective treatments in controlling
      the secondary injury that occurs after spinal cord injury, which substantially
      changes the prognosis. Low-intensity laser therapy (LILT) has been applied in
      neuroscience due to its anti-inflammatory effects on biological tissue in the
      repairing process. Few studies have been made associating LILT to the spinal cord
      injury. The objective of this study was to investigate the effect of the LILT
      (GaAlAs laser-780 nm) on the locomotor functional recovery, histomorphometric,
      and histopathological changes of the spinal cord after moderate traumatic injury
      in rats (spinal cord injury at T9 and T10). Thirty-one adult Wistar rats were
      used, which were divided into seven groups: control without surgery (n = 3),
      control surgery (n = 3), laser 6 h after surgery (n = 5), laser 48 h after
      surgery (n = 5), medullar lesion (n = 5) without phototherapy, medullar lesion +
      laser 6 h after surgery (n = 5), and medullar lesion + laser 48 h after surgery
      (n = 5). The assessment of the motor function was performed using Basso, Beattie,
      and Bresnahan (BBB) scale and adapted Sciatic Functional Index (aSFI). The
      assessment of urinary dysfunction was clinically performed. After 21 days
      postoperative, the animals were euthanized for histological and histomorphometric
      analysis of the spinal cord. The results showed faster motor evolution in rats
      with spinal contusion treated with LILT, maintenance of the effectiveness of the
      urinary system, and preservation of nerve tissue in the lesion area, with a
      notorious inflammation control and increased number of nerve cells and
      connections. In conclusion, positive effects on spinal cord recovery after
      moderate traumatic spinal cord injury were shown after LILT.

PMID- 24858234
TI  - The effect of low-level laser therapy (810 nm) on root development of immature
      permanent teeth in dogs.
AB  - Traumatic injuries and dental caries can be a big challenge to immature teeth. In
      these cases, the main purpose of treatment is to maintain the pulp vitality. The
      purpose of this study was to investigate the effect of low-level laser therapy on
      accelerating the rate of dentinogenesis in pulpotomy of immature permanent teeth
      (apexogenesis). Three dogs, 4-6 months old, were used in this study. One jaw in
      each dog was randomly assigned to laser irradiation group. All selected teeth
      were pulpotomized with mineral trioxide aggregate (MTA) and restored with
      amalgam. In the laser group, the Ga-Al-As laser (810 nm, 0.3 W, 4 J/cm(2), 9 s)
      was used on buccal and lingual gingiva of each tooth in 48 h intervals for 2
      weeks. In order to observe the newly formed dentine, tetracycline was injected on
      the 1st, 3rd, 7th, and 14th day after the operation. Then, ground sections of
      teeth were observed under a fluorescence microscope. The data was analyzed with
      Generalized Estimating Equations (GEE) test. The mean distance between the lines
      of tetracycline formed on the 1st and 14th day was significantly higher in the
      laser group (P = 0.005). Within the limitation of this study, irradiation of Ga
      Al-As laser (810 nm) can accelerate the rate of dentinogenesis in apexogenesis of
      immature permanent teeth with MTA in dogs.

PMID- 24858235
TI  - Effects of low-level laser therapy on mitochondrial respiration and nitrosyl
      complex content.
AB  - Among the photochemical reactions responsible for therapeutic effects of low
      power laser radiation, the photolysis of nitrosyl iron complexes of iron
      containing proteins is of primary importance. The purpose of the present study
      was to compare the effects of blue laser radiation on the respiration rate and
      photolysis of nitrosyl complexes of iron-sulfur clusters (NO-FeS) in
      mitochondria, subjected to NO as well as the possibility of NO transfer from NO
      FeS to hemoglobin. It was shown that mitochondrial respiration in State 3 (V3)
      and State 4 (V4), according to Chance, dramatically decreased in the presence of
      3 mM NO, but laser radiation (lambda = 442 nm, 30 J/cm(2)) restored the
      respiration rates virtually to the initial level. At the same time, electron
      paramagnetic resonance (EPR) spectra showed that laser irradiation decomposed
      nitrosyl complexes produced by the addition of NO to mitochondria. EPR signal of
      nitrosyl complexes of FeS-clusters, formed in the presence of 3 mM NO, was
      maximal in hypoxic mitochondria, and disappeared in a dose-dependent manner,
      almost completely at the irradiation dose 120 J/cm(2). EPR measurements showed
      that the addition of lysed erythrocytes to mitochondria decreased the amount of
      nitrosyl complexes in iron-sulfur clusters and produced the accumulation of NO
      hemoglobin. On the other hand, the addition of lysed erythrocytes to
      mitochondria, preincubated with nitric oxide, restored mitochondrial respiration
      rates V3 and V4 to initial levels. We may conclude that there are two possible
      ways to destroy FeS nitrosyl complexes in mitochondria and recover mitochondrial
      respiration inhibited by NO: laser irradiation and ample supply of the compounds
      with high affinity to nitric oxide, including hemoglobin.

PMID- 24858236
TI  - How do trained raters take context factors into account when assessing GP trainee
      communication performance? An exploratory, qualitative study.
AB  - Communication assessment in real-life consultations is a complex task. Generic
      assessment instruments help but may also have disadvantages. The generic nature
      of the skills being assessed does not provide indications for context-specific
      behaviour required in practice situations; context influences are mostly taken
      into account implicitly. Our research questions are: 1. What factors do trained
      raters observe when rating workplace communication? 2. How do they take context
      factors into account when rating communication performance with a generic rating
      instrument? Nineteen general practitioners (GPs), trained in communication
      assessment with a generic rating instrument (the MAAS-Global), participated in a
      think-aloud protocol reflecting concurrent thought processes while assessing
      videotaped real-life consultations. They were subsequently interviewed to answer
      questions explicitly asking them to comment on the influence of predefined
      contextual factors on the assessment process. Results from both data sources were
      analysed. We used a grounded theory approach to untangle the influence of context
      factors on GP communication and on communication assessment. Both from the think
      aloud procedure and from the interviews we identified various context factors
      influencing communication, which were categorised into doctor-related (17),
      patient-related (13), consultation-related (18), and education-related factors
      (18). Participants had different views and practices on how to incorporate
      context factors into the GP(-trainee) communication assessment. Raters
      acknowledge that context factors may affect communication in GP consultations,
      but struggle with how to take contextual influences into account when assessing
      communication performance in an educational context. To assess practice
      situations, raters need extra guidance on how to handle specific contextual
      factors. 

PMID- 24858238
TI  - Feeding motivation as a personality trait in Nile tilapia (Oreochromis
      niloticus): role of serotonergic neurotransmission.
AB  - Consistent individual variation in behaviour and physiology (i.e. animal
      personality or coping style) has emerged as a central topic in many biological
      disciplines. Yet, underlying mechanisms of crucial personality traits like
      feeding behaviour in novel environments remain unclear. Comparative studies,
      however, reveal a strong degree of evolutionary conservation of neural mechanisms
      controlling such behaviours throughout the vertebrate lineage. Previous studies
      have indicated duration of stress-induced anorexia as a consistent individual
      characteristic in teleost fishes. This study aims to determine to what degree
      brain 5-hydroxytryptamine (5-HT, serotonin) activity pertains to this aspect of
      animal personality, as a correlate to feed anticipatory behaviour and recovery of
      feed intake after transfer to a novel environment. Crucial to the definition of
      animal personality, a strong degree of individual consistency in different
      measures of feeding behaviour (feeding latency and feeding score), was
      demonstrated. Furthermore, low serotonergic activity in the hypothalamus was
      highly correlated with a personality characterized by high feeding motivation,
      with feeding motivation represented as an overall measure incorporating several
      behavioural parameters in a Principle Component Analyses (PCA). This study thus
      confirms individual variation in brain 5-HT neurotransmission as a correlate to
      complex behavioural syndromes related to feeding motivation. 

PMID- 24858239
TI  - Calcitriol promotes augmented dopamine release in the lesioned striatum of 6
      hydroxydopamine treated rats.
AB  - Current therapies for Parkinson's disease (PD) offer symptomatic relief but do
      not provide a cure or slow the disease process. Treatments that could halt
      progression of the disease or help restore function to damaged neurons would be
      of substantial benefit. Calcitriol, the active metabolite of vitamin D, has been
      shown to have significant effects on the brain. These effects include
      upregulating trophic factor levels, and reducing the severity of some central
      nervous system lesions. While previous studies have shown that calcitriol can be
      neuroprotective in 6-hydroxydopamine (6-OHDA) rodent models of PD, the present
      experiments were designed to examine the ability of calcitriol to promote
      restoration of extracellular dopamine (DA) levels and tissue content of DA in
      animals previously lesioned with 6-OHDA. Male Fischer-344 rats were given a
      single injection of 12 ug 6-OHDA into the right striatum. Four weeks later the
      animals were administered vehicle or calcitriol (0.3 or 1.0 ug/kg, s.c.) once a
      day for eight consecutive days. Three weeks after the calcitriol treatments in
      vivo microdialysis experiments were conducted to measure potassium and
      amphetamine evoked overflow of DA from both the left and right striata. In
      control animals treated with 6-OHDA and vehicle there were significant reductions
      in both potassium and amphetamine evoked overflow of DA on the lesioned side of
      the brain compared to the contralateral side. In animals treated with 6-OHDA
      followed by calcitriol there was significantly greater potassium and amphetamine
      evoked overflow of DA from the lesioned striatum compared to that from the
      control animals. The calcitriol treatments also led to increases in postmortem
      tissue levels of DA in the striatum and substantia nigra. These results suggest
      that calcitriol may help promote recovery of dopaminergic functioning in injured
      nigrostriatal neurons. 

PMID- 24858240
TI  - The dose-dependent antioxidant effects of physical exercise in the hippocampus of
      mice.
AB  - Exercise increases both the consumption of oxygen and the production of reactive
      species in biological tissues, and this is counterbalanced by antioxidant
      adaptations to regular physical training. When the intensity of exercise
      fluctuates between mild and moderate, it improves the status of reduction
      oxidation balance in the brain and induces neuroplasticity. However, intense
      exercise can oxidize the brain and impair neurological function. The effect of
      the frequency of exercise, which is an important factor in physical training, is
      still unknown. The effect of periodic exercise on biomarkers of oxidative stress
      in the hippocampus of mice was evaluated in this study. Mice were made to run on
      a treadmill for 8 weeks, two, three, or five times per week, and their hippocampi
      and quadriceps femoris muscles were then dissected. Biomarkers of oxidative
      damage were negatively correlated with the frequency of exercise and
      mitochondrial muscular activity, while the sulfhydryl contents were positively
      correlated with exercise frequency. A logistic analysis revealed a dose-dependent
      effect of exercise on these biomarkers. In summary, these results suggested that
      manipulating the frequency of physical exercise could induce antioxidant-related
      adaptations in the hippocampi of adult mice. 

PMID- 24858241
TI  - Effects of ferrofluid and phytoalexin spirobrassinin on thioflavin-T-based
      fluorescence in cerebrospinal fluid of the elderly and multiple sclerosis
      patients.
AB  - It is well known that misfolded peptides/proteins can play a role in processes of
      normal ageing and in the pathogenesis of many diseases including Alzheimer's
      disease. Previously, we evaluated samples of cerebrospinal fluid from patients
      with Alzheimer's disease and multiple sclerosis by means of thioflavin-T-based
      fluorescence. We observed attenuated effects of magnetite nanoparticles operated
      via anti-aggregation actions on peptides/proteins from patients with Alzheimer's
      disease but not from those with multiple sclerosis when compared to age-related
      controls. In this study, we have evaluated the in vitro effects of anti
      aggregation operating ferrofluid and phytoalexin spirobrassinin in the
      cerebrospinal fluid of patients with multiple sclerosis and Alzheimer's disease.
      We have found significant differences in native fluorescence (lambda excitation =
      440 nm, lambda emission = 485 nm) of samples among particular groups (young
      controls < multiple sclerosis, Alzheimer's disease < old controls). Differences
      among groups were observed also in thioflavin-T-based fluorescence (young
      controls = multiple sclerosis < Alzheimer's disease < old controls) and the most
      marked change from native to thioflavin-T-based fluorescence was found in young
      controls (28-40 years old people). Both ferrofluid and spirobrassinin evoked
      drops in thioflavin-T-based fluorescence; however, ferrofluid was more efficient
      in old controls (54-75 years old people) and spirobrassinin in multiple sclerosis
      patients, both compared to young controls. The results are discussed especially
      in relation to aggregated peptides/proteins and liposoluble fluorescent products
      of lipid peroxidation. Based on the significant effect of spirobrassinin in
      vitro, we suggest that spirobrassinin may be of therapeutic value in multiple
      sclerosis. 

PMID- 24858242
TI  - Genomics and epigenomics in pediatric oncology and clinical laboratory genetics.

PMID- 24858243
TI  - A synopsis of methods of sweat tests in pathology.

PMID- 24858244
TI  - The concept of oral tolerance induction to foods.

PMID- 24858246
TI  - The organisation of training for laboratory scientists in inherited metabolic
      disease, newborn screening and paediatric clinical chemistry.

PMID- 24858245
TI  - Urine metabolomic profiling in neonatal nephrology.
AB  - Metabolomics, the latest "omics" technology aims to study the complete set of low
      molecular weight metabolites that may change according to the physiological or
      the pathological state of the organism. Clinical studies dealing with
      metabolomics in neonatal and pediatric nephrology are very few. In this paper we
      present the experimental studies in newborn animal models, together with the
      available data on human newborns. Finally the urine metabolomic profiling of 3
      newborns who suffered from severe perinatal asphyxia and were treated with
      hypothermia. They are located in a different part of the multivariate space, the
      reason of the differences being the basal metabolic profile (resilience) of each
      neonate: 1 died and 2 survived (one of them developed an acute kidney injury).
      The main metabolites responsible for the different metabolic profile among the 3
      newborns are presented. In the future each neonatologist and nephrologist should
      become skilled in the metabolomic field. 

PMID- 24858247
TI  - Promoting healthy growth and nutrition in preterm infants: a challenge for
      clinicians and researchers.

PMID- 24858249
TI  - Measurement of hydroxyproline in collagen with three different methods.
AB  - Determination of the 4-hydroxy-l-proline (hydroxyproline) concentration may
      provide useful information for the diagnosis and prognosis of diseases caused by
      disorders of collagen metabolism. The objective of the present study was to apply
      liquid chromatography-mass spectrometry (LC-MS) to assess the hydroxyproline
      concentration. The hydroxyproline concentration in lung and liver tissues
      measured by LC-MS was compared with values obtained by a colorimetric method, as
      well as a fluorescence method using high-performance liquid chromatography (HPLC)
      from previous studies by our group. The determination of the hydroxyproline
      concentration by LC-MS was improved as compared with that using the colorimetric
      and HPLC methods, due to its simplicity, high sensitivity (pg level) and short
      separation time. These results suggested that utilizing the LC-MS method for
      measuring the hydroxyproline concentration would be advantageous for the
      diagnosis of diseases associated with abnormalities of collagen metabolism. 

PMID- 24858252
TI  - Exploring molecular structures, orbital interactions, intramolecular proton
      transfer reaction kinetics, electronic transitions and complexation of 3
      hydroxycoumarin species using DFT methods.
AB  - Optimal structures and electronic properties of various species of 3
      hydroxycoumarin (3-HCou) have been explored using density functional theory (DFT)
      methods under polarizable continuum model (PCM) of solvation. Electron transfer
      from pyrone to benzene moieties is enhanced upon deprotonation. Anionic and
      radical species have similar orbital-interaction characteristics but the charges
      in the former are distributed more uniformly. The rate of intramolecular proton
      transfer for the neutral species increases many folds upon excitation. The HOMO
      LUMO transition with pi->pi* character mainly accounts for the UV absorption of
      most 3-HCou species in solution. The wavelengths of maximal absorption predicted
      using TD-DFT method are in agreement with the previous experiment. For the
      charged species, calculations with the range-corrected functional yield better
      agreement with the previous experiment. Anionic 3-HCou species shows high degrees
      of complexation with chromium(III) and copper(II) compared with oxovanadium(IV)
      and zinc(II). Either oxovanadium(IV) or zinc(II) prefers forming two isomeric
      complexes with comparable degrees of formation. 

PMID- 24858253
TI  - A single amino acid change humanizes long-chain fatty acid binding and activation
      of mouse peroxisome proliferator-activated receptor alpha.
AB  - Peroxisome proliferator-activated receptor alpha (PPARalpha) is an important
      regulator of hepatic lipid metabolism which functions through ligand binding.
      Despite high amino acid sequence identity (>90%), marked differences in PPARalpha
      ligand binding, activation and gene regulation have been noted across species.
      Similar to previous observations with synthetic agonists, we have recently
      reported differences in ligand affinities and extent of activation between human
      PPARalpha (hPPARalpha) and mouse PPARalpha (mPPARalpha) in response to long chain
      fatty acids (LCFA). The present study was aimed to determine if structural
      alterations could account for these differences. The binding of PPARalpha to LCFA
      was examined through in silico molecular modeling and docking simulations.
      Modeling suggested that variances at amino acid position 272 are likely to be
      responsible for differences in saturated LCFA binding to hPPARalpha and
      mPPARalpha. To confirm these results experimentally, LCFA binding, circular
      dichroism, and transactivation studies were performed using a F272I mutant form
      of mPPARalpha. Experimental data correlated with in silico docking simulations,
      further confirming the importance of amino acid 272 in LCFA binding. Although the
      driving force for evolution of species differences at this position are yet
      unidentified, this study enhances our understanding of ligand-induced regulation
      by PPARalpha and demonstrates the efficacy of molecular modeling and docking
      simulations. 

PMID- 24858254
TI  - Using thermodynamic integration MD simulation to compute relative protein-ligand
      binding free energy of a GSK3beta kinase inhibitor and its analogs.
AB  - Thermodynamic integration molecular dynamics simulation was used to investigate
      how TI-MD simulation preforms in reproducing relative protein-ligand binding free
      energy of a pair of analogous GSK3beta kinase inhibitors of available
      experimental data (see Fig. 1), and to predict the affinity for other analogs.
      The computation for the pair gave a DeltaDeltaG of 1.0 kcal/mol, which was in
      reasonably good agreement with the experimental value of -0.1 kcal/mol. The error
      bar was estimated at 0.5 kcal/mol. Subsequently, we employed the same protocol to
      proceed with simulations to find analogous inhibitors with a stronger affinity.
      Four analogs with a substitution at one site inside the binding pocket were the
      first to be tried, but no significant enhancement in affinity was found.
      Subsequent simulations for another 7 analogs was focused on substitutions at the
      benzene ring of another site, which gave two analogs (analogs 9 and 10) with
      DeltaDeltaG values of -0.6 and -0.8 kcal/mol, respectively. Both analogs had a OH
      group at the meta position and another OH group at the ortho position at the
      other side of the benzene ring, as shown in Table 3. To explore further, another
      4 analogs with this characteristic were investigated. Three analogs with
      DeltaDeltaG values of -2.2, -1.7 and -1.2 kcal/mol, respectively, were found.
      Hydrogen bond analysis suggested that the additional hydrogen bonds of the added
      OH groups with Gln185 and/or Asn64, which did not appear in the reference
      inhibitor or as an analog with one substitution only in the examined cases, were
      the main contributors to an enhanced affinity. A prediction for better inhibitors
      should interest experimentalists of enzyme and/or cell assays. Analysis of the
      interactions between GSK3beta kinase and the investigated analogs will be useful
      in the design of GSK3beta kinase inhibitors for compounds of this class.

PMID- 24858255
TI  - Mechanistic investigation of the reactivity of disilene with nitrous oxide: A DFT
      study.
AB  - We have reported the mechanistic investigation of the reaction of N2O addition to
      disilene, trans-[(TMS)2N(eta(1)-Me5C5)SiSi(eta(1)-Me5C5)N(TMS)2] (1t), employing
      density functional theory (BP86/TZVP//BP86/SVP) calculations. The potential
      energy surfaces of the title reaction are broadly classified under three
      pathways. Pathway I deals with the direct N2O additions to 1t affording the trans
      dioxadisiletane ring compound Pt whereas in the same pathway we report a
      different bifurcation route from intermediate 2t. This route portrays the
      isomerization of trans-monooxadisiletane species 2t prior to the second N2O
      addition, finally leading to the cis-isomeric product Pc. Different possibilities
      for isomerization of disilene 1t to 1c were studied in pathway II. The cis
      disilene (1c) formed can subsequently react with two N2O molecules affording the
      cis-product Pc. Pathway III details the formation of silanone type intermediate
      6, which subsequently combine with another silanone to afford loosely bound
      intermediates 7 and 8 respectively. The two separated silanone fragments in the
      isomeric intermediates 7 and 8 can then dimerizes to furnish the desired
      products. Among all the calculated potential energy surfaces, pathway III remains
      the most preferred route for disilene oxygenation under normal experimental
      condition. The present investigation about disilene reactivity will provide a
      deeper understanding on silylene chemistry and will exhibit promising
      applicability in main group chemistry as a whole. 

PMID- 24858256
TI  - Group-based QSAR and molecular dynamics mechanistic analysis revealing the mode
      of action of novel piperidinone derived protein-protein inhibitors of p53-MDM2.
AB  - Tumour suppressor p53 is known to play a central role in prevention of tumour
      development, DNA repair, senescence and apoptosis which is in normal cells
      maintained by negative feedback regulator MDM2 (Murine Double Minute 2). In case
      of dysfunctioning of this regulatory loop, tumour development starts thus
      resulting in cancerous condition. Inhibition of p53-MDM2 binding would result in
      activation of the tumour suppressor. In this study, a novel robust fragment-based
      QSAR model has been developed for piperidinone derived compounds experimentally
      known to inhibit p53-MDM2 interaction. The QSAR model developed showed
      satisfactory statistical parameters for the experimentally reported dataset
      (r(2)=0.9415, q(2)=0.8958, pred_r(2)=0.8894 and F-test=112.7314), thus judging
      the robustness of the model. Low standard error values (r(2)_se=0.3003,
      q(2)_se=0.4009 and pred_r(2)_se=0.3315) confirmed the accuracy of the developed
      model. The regression equation obtained constituted three descriptors (R2
      DeltaEpsilonA, R1-RotatableBondCount and R2-SssOCount), two of which had positive
      contribution while third showed negative correlation. Based on the developed QSAR
      model, a combinatorial library was generated and activities of the compounds were
      predicted. These compounds were docked with MDM2 and two top scoring compounds
      with binding affinities of -10.13 and -9.80kcal/mol were selected. The binding
      modes of actions of these complexes were analyzed using molecular dynamics
      simulations. Analysis of the developed fragment-based QSAR model revealed that
      addition of unsaturated electronegative groups at R2 site and groups with more
      rotatable bonds at R1 improved the inhibitory activity of these potent lead
      compounds. The detailed analysis carried out in this study provides a
      considerable basis for the design and development of novel piperidinone-based
      lead molecules against cancer and also provides mechanistic insights into their
      mode of actions. 

PMID- 24858257
TI  - A randomized clinical study on optimum proposal of integration of disease and
      syndrome to treat viral myocarditis.
AB  - OBJECTIVE: To determine the optimum treatment for viral myocarditis (VMC).
      METHODS: A total of 126 VMC patients were randomly divided into the control group
      (42 cases) that was treated with conventional Western medicine, and the
      intervention group (84 cases) that was treated with a combination of Chinese
      medicine (CM) and Western medicine intervention termed optimum proposal of
      integration of disease and syndrome (OPIDS). Before and after 4 weeks of
      treatment, the integral of CM syndrome, self-rating depression and anxiety scales
      (SDS and SAS, respectively), echocardiograms (ECGs), heart rate variability and
      left ventricular systolic function were observed. RESULTS: Compared with the
      control group, the intervention group showed significant reductions on the SDS
      and SAS (P <0.05); improvement of premature ventricular beats, atrioventricular
      blocks, ST-segment abnormalities, and significant T wave changes (P <0.05);
      greater reductions in standard deviation of NN intervals (SDNN), standard
      deviation for per 5 min averages NN intervals (SDANN), and root-mean-square of
      successive difference of NN intervals (rMSSD) (P <0.05); and increases in cardiac
      output, stroke volume, and ejection fraction, the last of which was statistically
      significant (P <0.05). Overall, the treatment efficacy rate was significantly
      better P<0.05) in the intervention group (75.61%) compared with the control group
      (69.70%). CONCLUSION: OPIDS is quite effective in treating VMC and improves
      symptoms such as anxiety and depression, left ventricular systolic dysfunction,
      premature ventricular contraction, and cardiac autonomic nervous system
      dysfunction. [ REGISTRATION: Chinese clinical trial center (No. ChiCTR-TRC
      00000298)].

PMID- 24858258
TI  - Rapid development of squamous cell carcinoma after photodynamic therapy.

PMID- 24858259
TI  - Spotlighting the role of photodynamic therapy in cutaneous malignancy: an update
      and expansion.

PMID- 24858260
TI  - Free app for consultation imaging.

PMID- 24858261
TI  - A Trichosanthin-derived peptide suppresses type 1 immune responses by TLR2
      dependent activation of CD8(+)CD28(-) Tregs.
AB  - A group of 15-aa-long Trichosanthin-derived peptides was synthesized and screened
      based on their differential abilities to induce low-responsiveness in mouse
      strains with high and low susceptibility. One of them was conjugated to form a
      homo-tetramer Tk-tPN. At concentrations of 0.1-50 MUg/ml, Tk-tPN activated
      CD8(+)CD28(-) Tregs in vitro to induce immune suppression as effectively as the
      native Trichosanthin but did not exhibit cytotoxicity. In EAE mice which were pre
      treated with Tk-tPN or Tk-tPN-activated CD8(+) T cells, a marked attenuation of
      clinical scores was recorded together with an expansion of the CD8(+)CD28(-) Treg
      from 2.2% to 36.1% in vivo. A pull-down assay and signal transduction analyses
      indicated that the ability of Tk-tPN to convert the CD8(+)CD28(-) Treg-related
      cytokine secretion pattern from type 1 to type 2 depends on the TLR2-initiated
      signaling in macrophages. The high production of IL-4/IL-10 by the Tk-tPN
      activated CD8(+)CD28(-) Treg suggests the value of using Tk-tPN as a therapeutic
      reagent for Th1-dominant immunological diseases.

PMID- 24858262
TI  - Simultaneous determination of four sulfur mustard-DNA adducts in rabbit urine
      after dermal exposure by isotope-dilution liquid chromatography-tandem mass
      spectrometry.
AB  - Sulfur mustard (SM) is a classic vesicant agent, which has been greatly employed
      in several wars or military conflicts. The most lesion mechanism is its strong
      alkylation of DNAs in vivo. Until now there are four specific DNA adducts of SM
      identified for further retrospective detection, i.e., N(7)-(2
      hydroxyethylthioethyl)-2'-guanine (N(7)-HETEG), bis(2-ethyl-N(7)
      guanine)thioether (Bis-G), N(3)-(2-hydroxyethylthioethyl)-2'-adenine (N(3)-HETEA)
      and O(6)-(2-hydroxyethylthioethyl)-2'-guanine (O(6)-HETEG), respectively. Here, a
      novel and sensitive method of isotope-dilution ultrahigh performance liquid
      chromatography-tandem mass spectrometry (UPLC-MS/MS) combining with solid phase
      extraction was reported for the simultaneous determination of four SM-DNA
      adducts. A lower limit of detection of 2-5ngL(-1), and a lower limit of
      quantitation of 5-10ngL(-1) were achieved, respectively, and the recoveries
      ranged from 87% to 116%. We applied this method in the determination of four SM
      DNA adducts in rabbit urine after dermal exposure by SM in three dose levels (2,
      5, 15mgkg(-1)), so as to investigate the related metabolic behavior in vivo. For
      the first time, in SM exposed rabbit urine, our results revealed the relative
      accumulation abundance of four SM-DNA adducts, i.e., 67.4% for N(7)-HETEG, 22.7%
      for Bis-G, 9.8% for N(3)-HETEA, 0.1% for O(6)-HETEG, and significant dose and
      time dependent responses of these SM-DNA adducts. The four adducts were
      detectable after 8h, afterwards, their contents continuously increased, achieved
      maximum in the first two or three days and then gradually decreased till the end
      of one month. Meanwhile, the amounts of SM-DNA adducts were positively correlated
      with the exposure doses. 

PMID- 24858263
TI  - Determination of homocysteine thiolactone in urine by field amplified sample
      injection and sweeping MEKC method with UV detection.
AB  - Homocysteine thiolactone (Hcy-thiolactone), an intramolecular thioester, easily
      acylates free-amino groups in proteins, which impairs or alters the protein's
      biological function. Here, we describe new capillary electrophoresis assay for
      the determination of Hcy-thiolactone in human urine based on a field amplified
      sample injection and sweeping MEKC with UV detection. The two steps procedure
      relies on sample liquid-liquid extraction followed by CE separation and UV
      detection at 240nm. The Hcy-thiolactone standard added to the urine before the
      extraction step shows that the response of the detector is linear within the
      range studied, from 0.1 to 1MUmolL(-1) urine. The intra- and interday precision
      and recovery were 3.2-14.4% (average 5.1% and 9.3%) and 92.5-112.6% (average
      99.8% and 99.1%), respectively. The lower limit of quantification was 0.09nmol
      Hcy-thiolactone in 1mL of urine. The proposed method was applied for the analysis
      of 15 urine samples donated by apparently healthy volunteers. The average
      concentration of the analyte was 0.170+/-0.029MUmolL(-1). 

PMID- 24858264
TI  - Quantitative determination of the anti-tumor agent tasquinimod in human urine by
      liquid chromatography-tandem mass spectrometry.
AB  - Tasquinimod is an anti-tumor drug that is currently in clinical development for
      the treatment of solid cancers. After oral administration, tasquinimod and a
      number of its metabolites are excreted in the urine. The quantitative
      determination of tasquinimod in urine is challenging because of the required
      sensitivity (down to 0.1nM or 40pg/mL), the highly variable nature of this
      biological matrix and the presence of potentially unstable metabolites, which may
      convert back to the parent drug. In this article, an LC-MS/MS method is described
      for the determination of tasquinimod in human urine in the concentration range
      0.1-200nM. Liquid-liquid extraction with n-chlorobutane was used to extract
      tasquinimod from 100MUL human urine and to remove interfering endogenous urinary
      constituents. Reversed-phase liquid chromatography coupled to a triple quadrupole
      mass spectrometer equipped with an ESI source was used for quantification of
      tasquinimod in a 2.5-min run. A stable-isotope labeled internal standard was used
      for response normalization. The intra- and inter-day coefficients of variation
      (precision) as well as the bias (accuracy) of the method were below 7%. Although
      considerable conversion of conjugated tasquinimod metabolites back to parent drug
      was observed when incurred samples were stored at 37 degrees C for a prolonged
      time, tasquinimod as well as its metabolites were sufficiently stable under all
      relevant sampling, storage and analysis conditions. The method was successfully
      applied to determine the urinary excretion of tasquinimod in healthy volunteers
      and patients with renal impairment after a 0.5-mg oral dose. 

PMID- 24858265
TI  - Synthesis of silver nanoparticles by green method stabilized to synthetic human
      stomach fluid.
AB  - Silver nanoparticles (Ag NP) have been attracted much attention in recent years
      in biomedical applications due to their antimicrobial activity, but their
      drawbacks include toxicity and instability to aqueous hydrochloric acid
      solutions. Ag NPs have now been successfully prepared by a simple and "green"
      synthesis method by reducing Ag+ ions in the presence of modified poly(vinyl
      alcohol) thiol (PVA-SH) in aqueous acidic solution. In this respect, Ag NPs were
      stabilized by coating different types of citrate-reduced Ag NPs with different
      weight ratios (1-3 Wt. %) of PVSH derivatives. The as-prepared Ag NPs were
      characterized using UV-Visible, high resolution transmission electron microscopy/
      energy dispersive X-ray spectroscopy (TEM/EDS), dynamic light scattering (DLS)
      and X-ray powder diffraction (XRD) combined with Rietveld analysis. The changes
      in size, shape, and hydrodynamic diameter of Ag NPs after different duration
      exposure to synthetic stomach fluid (SSF) and1 M HCl were determined using TEM,
      XRD and UV-Visible analyses. The data indicated that these Ag NPs possessed high
      stability to SSF for more than 90 days, which was not previously reported in the
      literature. 

PMID- 24858266
TI  - A facile route to tailoring peptide-stabilized gold nanoparticles using
      glutathione as a synthon.
AB  - The preparation of gold nanoparticles (AuNPs) of high purity and stability
      remains a major challenge for biological applications. This paper reports a
      simple synthetic strategy to prepare water-soluble peptide-stabilized AuNPs.
      Reduced glutathione, a natural tripeptide, was used as a synthon for the growth
      of two peptide chains directly on the AuNP surface. Both nonpolar (tryptophan and
      methionine) and polar basic (histidine and dansylated arginine) amino acids were
      conjugated to the GSH-capped AuNPs. Ultracentrifugation concentrators with
      polyethersulfone (PES) membranes were used to purify precursor materials in each
      stage of the multi-step synthesis to minimize side reactions. Thin layer
      chromatography, transmission electron microscopy, UV-Visible, 1H-NMR, and
      fluorescence spectroscopies demonstrated that ultracentrifugation produces high
      purity AuNPs, with narrow polydispersity, and minimal aggregation. More
      importantly, it allows for more control over the composition of the final ligand
      structure. Studies under conditions of varying pH and ionic strength revealed
      that peptide length, charge, and hydrophobicity influence the stability as well
      as solubility of the peptide-capped AuNPs. The synthetic and purification
      strategies used provide a facile route for developing a library of tailored
      biocompatible peptide-stabilized AuNPs for biomedical applications. 

PMID- 24858267
TI  - Applications of liquid-phase microextraction in the sample preparation of
      environmental solid samples.
AB  - Solvent extraction remains one of the fundamental sample preparation techniques
      in the analysis of environmental solid samples, but organic solvents are toxic
      and environmentally harmful, therefore one of the possible greening directions is
      its miniaturization. The present review covers the relevant research from the
      field of application of microextraction to the sample preparation of
      environmental solid samples (soil, sediments, sewage sludge, dust etc.) published
      in the last decade. Several innovative liquid-phase microextraction (LPME)
      techniques that have emerged recently have also been applied as an aid in sample
      preparation of these samples: single-drop microextraction (SDME), hollow fiber
      liquid phase microextraction (HF-LPME), dispersive liquid-liquid microextraction
      (DLLME). Besides the common organic solvents, surfactants and ionic liquids are
      also used. However, these techniques have to be combined with another technique
      to release the analytes from the solid sample into an aqueous solution. In the
      present review, the published methods were categorized into three groups: LPME in
      combination with a conventional solvent extraction; LPME in combination with an
      environmentally friendly extraction; LPME without previous extraction. The
      applicability of these approaches to the sample preparation for the determination
      of pollutants in solid environmental samples is discussed, with emphasis on their
      strengths, weak points and environmental impact. 

PMID- 24858268
TI  - Avicequinone C isolated from Avicennia marina exhibits 5alpha-reductase-type 1
      inhibitory activity using an androgenic alopecia relevant cell-based assay
      system.
AB  - Avicennia marina (AM) exhibits various biological activities and has been
      traditionally used in Egypt to cure skin diseases. In this study, the methanolic
      heartwood extract of AM was evaluated for inhibitory activity against 5alpha
      reductase (5alpha-R) [E.C.1.3.99.5], the enzyme responsible for the over
      production of 5alpha-dihydrotestosterone (5alpha-DHT) causing androgenic alopecia
      (AGA). An AGA-relevant cell-based assay was developed using human hair dermal
      papilla cells (HHDPCs), the main regulator of hair growth and the only cells
      within the hair follicle that are the direct site of 5alpha-DHT action, combined
      with a non-radioactive thin layer chromatography (TLC) detection technique. The
      results revealed that AM is a potent 5alpha-R type 1 (5alpha-R1) inhibitor,
      reducing the 5alpha-DHT production by 52% at the final concentration of 10 ug/mL.
      Activity-guided fractionation has led to the identification of avicequinone C, a
      furanonaphthaquinone, as a 5alpha-R1 inhibitor with an IC50 of 9.94 +/- 0.33
      ug/mL or 38.8 +/- 1.29 uM. This paper is the first to report anti-androgenic
      activity through 5alpha-R1 inhibition of AM and avicequinone C. 

PMID- 24858269
TI  - Synthesis and antibacterial activity of amino acid and dipeptide prodrugs of IMB
      070593, a fluoroquinolone candidate.
AB  - A series of amino acid and dipeptide prodrugs of IMB-070593, a fluoroquinolone
      candidate discovered in our lab, were synthesized and evaluated for their water
      solubility and then antibacterial activity. Our results reveal that four amino
      acid prodrugs 4a,b,e,f and two dipeptide prodrugs 4k,l have much greater
      solubility (>85 mg/mL) than IMB-070593 mesylate (22.5 mg/mL). Compounds 4a and 4k
      show good in vivo efficacy against MSSA 12-1 (p.o./i.v., 5.32-7.68 mg/kg) and S.
      pneumoniae12-10 (p.o., 18.39-23.13 mg/kg) which is 1.19-1.50 fold more active
      than the parent drug. 

PMID- 24858270
TI  - A new diterpene from Litsea cubeba fruits: structure elucidation and capability
      to induce apoptosis in HeLa cells.
AB  - A new diterpene, identified as (+)-6-(4-hydroxy-4-methyl-2-pentenoyl)-4,6
      dimethyl-5-(3-methyl-2-butenyl)-1,3-cyclohexadienecarbaldehyde (1, cubelin), was
      isolated from a methanol extract of Litsea cubeba fruits by normal phase column
      chromatography and purified by preparative HPLC. The structure elucidation was
      conducted by spectroscopic methods (UV, IR, ESI-TOF-MS, 1-D and 2-D NMR). Cubelin
      exhibited activity against HeLa cell viability and proliferation. The cells also
      exhibited changes in nuclear morphology which are hallmarks of apoptotic cell
      death. The presence of cleaved caspase-3/-7, caspase-8 and caspase-9 in the
      cubelin treated population indicated the potential of the compound to induce
      apoptosis in HeLa cells via both intrinsic and extrinsic pathways. 

PMID- 24858271
TI  - Associations of nm23H1, VEGF-C, and VEGF-3 receptor in human prostate cancer.
AB  - We studied the expression of the non-metastatic clone 23 type 1 (nm23H1) gene,
      vascular endothelial growth factor (VEGF)-C, and its receptor VEGFR-3 using an in
      situ hybridization technique and immunohistochemical analyses with prostate
      cancer tissues and adjacent benign tissues of 52 human archival cases. The
      association between VEGF-C expression, microlymphatic count (MLC), and staining
      intensity for nm23H1 and VEGFR-3 was used to evaluate tumor metastasis and
      survival rate. MLC values were significantly higher in tumorous tissue than in
      non-cancerous tissue. VEGF-C mRNA, VEGFR-3, and nm23H1 were highly expressed in
      tumorous tissue. VEGFR-3 expression was greater in VEGF-C mRNA-positive tumors
      than in VEGF-C mRNA-negative tumors. The association of VEGFR-3 expression with
      VEGF-C mRNA and MLC suggested that the poor prognosis and tumor metastasis
      associated with VEGFR-3 expression may be due, in part, to its role in promoting
      angiogenesis. VEGF-C expression was significantly associated with tumor
      lymphangiogenesis, angiogenesis, and immune response as a potent multifunctional
      stimulating factor in prostate cancer. Expression of nm23H1 was significantly
      inversely correlated with lymph node metastasis. Furthermore, there was a strong
      negative correlation between the expression of nm23H1, VEGF-C mRNA, and MLC.
      These findings provide important information for prophylactic, diagnostic, and
      therapeutic strategies for prostate cancer. 

PMID- 24858272
TI  - Calcium influx inhibition is involved in the hypotensive and vasorelaxant effects
      induced by yangambin.
AB  - The pharmacological effects on the cardiovascular system of yangambin, a lignan
      isolated from Ocotea duckei Vattimo (Lauraceae), were studied in rats using
      combined functional and biochemical approaches. In non-anaesthetized rats,
      yangambin (1, 5, 10, 20, 30 mg/kg, i.v.) induced hypotension (-3.5 +/- 0.2; -7.1
      +/- 0.8; -8.9 +/- 1.3; -14 +/- 2.3, -25.5% +/- 2.6%, respectively) accompanied by
      tachycardia (5.9 +/- 0.5; 5.9 +/- 1.6; 8.8 +/- 1.4; 11.6, 18.8% +/- 3.4%,
      respectively). In isolated rat atria, yangambin (0.1 uM-1 mM) had very slight
      negative inotropic (Emax = 35.6% +/- 6.4%) and chronotropic effects (Emax = 10.2%
      +/- 2.9%). In endothelium-intact rat mesenteric artery, yangambin (0.1 uM-1 mM)
      induced concentration-dependent relaxation (pD2 = 4.5 +/- 0.06) of contractions
      induced by phenylephrine and this effect was not affected by removal of the
      endothelium. Interestingly, like nifedipine, the relaxant effect induced by
      yangambin was more potent on the contractile response induced by KCl 80 mM (pD2 =
      4.8 +/- 0.05) when compared to that induced by phenylephrine. Furthermore,
      yangambin inhibited CaCl2-induced contractions in a concentration-dependent
      manner. This lignan also induced relaxation (pD2 = 4.0 +/- 0.04) of isolated
      arteries pre-contracted with S(-)-Bay K 8644. In fura-2/AM-loaded myocytes of rat
      mesenteric arteries, yangambin inhibited the Ca2+ signal evoked by KCl 60 mM. In
      conclusion, these results suggest that the hypotensive effect of yangambin is
      probably due to a peripheral vasodilatation that involves, at least, the
      inhibition the Ca2+ influx through voltage-gated Ca2+ channels. 

PMID- 24858273
TI  - Two-stage prediction of the effects of imidazolium and pyridinium ionic liquid
      mixtures on luciferase.
AB  - The predicted toxicity of mixtures of imidazolium and pyridinium ionic liquids
      (ILs) in the ratios of their EC50, EC10, and NOEC (no observed effect
      concentration) were compared to the observed toxicity of these mixtures on
      luciferase. The toxicities of EC50 ratio mixture can be effectively predicted by
      two-stage prediction (TSP) method, but were overestimated by the concentration
      addition (CA) model and underestimated by the independent action (IA) model. The
      toxicities of EC10 ratio mixtures can be basically predicted by TSP and CA, but
      were underestimated by IA. The toxicities of NOEC ratio mixtures can be predicted
      by TSP and CA in a certain concentration range, but were underestimated by IA.
      Our results support the use of TSP as a default approach for predicting the
      combined effect of different types of ILs at the molecular level. In addition,
      mixtures of ILs mixed at NOEC and EC10 could cause significant effects of 64.1%
      and 97.7%, respectively. Therefore, we should pay high attention to the combined
      effects in mixture risk assessment. 

PMID- 24858274
TI  - Circulating miRNAs as biomarkers for neurodegenerative disorders.
AB  - Neurodegenerative disorders, such as Alzheimer's disease (AD), Parkinson's
      disease (PD) and frontotemporal dementias (FTD), are considered distinct
      entities, however, there is increasing evidence of an overlap from the clinical,
      pathological and genetic points of view. All neurodegenerative diseases are
      characterized by neuronal loss and death in specific areas of the brain, for
      example, hippocampus and cortex for AD, midbrain for PD, frontal and temporal
      lobes for FTD. Loss of neurons is a relatively late event in the progression of
      neurodegenerative diseases that is typically preceded by other events such as
      metabolic changes, synaptic dysfunction and loss, neurite retraction, and the
      appearance of other abnormalities, such as axonal transport defects. The brain's
      ability to compensate for these dysfunctions occurs over a long period of time
      and results in late clinical manifestation of symptoms, when successful
      pharmacological intervention is no longer feasible. Currently, diagnosis of AD,
      PD and different forms of dementia is based primarily on analysis of the
      patient's cognitive function. It is therefore important to find non-invasive
      diagnostic methods useful to detect neurodegenerative diseases during early,
      preferably asymptomatic stages, when a pharmacological intervention is still
      possible. Altered expression of microRNAs (miRNAs) in many disease states,
      including neurodegeneration, and increasing relevance of miRNAs in biofluids in
      different pathologies has prompted the study of their possible application as
      neurodegenerative diseases biomarkers in order to identify new therapeutic
      targets. Here, we review what is known about the role of miRNAs in the
      pathogenesis of neurodegeneration and the possibilities and challenges of using
      these small RNA molecules as a signature for neurodegenerative conditions. 

PMID- 24858276
TI  - MicroRNA-1 regulates chondrocyte phenotype by repressing histone deacetylase 4
      during growth plate development.
AB  - MicroRNAs (miRs) are noncoding RNAs (17-25 nt) that control translation and/or
      mRNA degradation. Using Northern blot analysis, we identified that miR-1 is
      specifically expressed in growth plate cartilage in addition to muscle tissue,
      but not in brain, intestine, liver, or lung. We obtained the first evidence that
      miR-1 is highly expressed in the hypertrophic zone of the growth plate, with an 8
      fold increase compared with the proliferation zone; this location coincides with
      the Ihh and Col X expression regions in vivo. MiR-1 significantly induces
      chondrocyte proliferation and differentiation. We further identified histone
      deacetylase 4 (HDAC4) as a target of miR-1. HDAC4 negatively regulates
      chondrocyte hypertrophy by inhibiting Runx2, a critical transcription factor for
      chondrocyte hypertrophy. MiR-1 inhibits both endogenous HDAC4 protein by 2.2-fold
      and the activity of a reporter gene bearing the 3'-untranslated region (UTR) of
      HDAC4 by 3.3-fold. Conversely, knockdown of endogenous miR-1 relieves the
      repression of HDAC4. Deletion of the miR-1 binding site in HDAC4 3'-UTR or
      mutated miR-1 abolishes miR-1-mediated inhibition of the reporter gene activity.
      Overexpression of HDAC4 reverses miR-1 induction of chondrocyte differentiation
      markers Col X and Ihh. HDAC4 inhibits Runx2 promoter activity in a dosage
      dependent manner. Thus, miR-1 plays an important role in the regulation of the
      chondrocyte phenotype during the growth plate development via direct targeting of
      HDAC4.

PMID- 24858277
TI  - Knockdown of estrogen receptor-alpha induces autophagy and inhibits antiestrogen
      mediated unfolded protein response activation, promoting ROS-induced breast
      cancer cell death.
AB  - Approximately 70% of all newly diagnosed breast cancers express estrogen receptor
      (ER)-alpha. Although inhibiting ER action using targeted therapies such as
      fulvestrant (ICI) is often effective, later emergence of antiestrogen resistance
      limits clinical use. We used antiestrogen-sensitive and -resistant cells to
      determine the effect of antiestrogens/ERalpha on regulating autophagy and
      unfolded protein response (UPR) signaling. Knockdown of ERalpha significantly
      increased the sensitivity of LCC1 cells (sensitive) and also resensitized LCC9
      cells (resistant) to antiestrogen drugs. Interestingly, ERalpha knockdown, but
      not ICI, reduced nuclear factor (erythroid-derived 2)-like (NRF)-2 (UPR-induced
      antioxidant protein) and increased cytosolic kelch-like ECH-associated protein
      (KEAP)-1 (NRF2 inhibitor), consistent with the observed increase in ROS
      production. Furthermore, autophagy induction by antiestrogens was prosurvival but
      did not prevent ERalpha knockdown-mediated death. We built a novel mathematical
      model to elucidate the interactions among UPR, autophagy, ER signaling, and ROS
      regulation of breast cancer cell survival. The experimentally validated
      mathematical model explains the counterintuitive result that knocking down the
      main target of ICI (ERalpha) increased the effectiveness of ICI. Specifically,
      the model indicated that ERalpha is no longer present in excess and that the
      effect on proliferation from further reductions in its level by ICI cannot be
      compensated for by increased autophagy. The stimulation of signaling that can
      confer resistance suggests that combining autophagy or UPR inhibitors with
      antiestrogens would reduce the development of resistance in some breast cancers.

PMID- 24858278
TI  - Regulation of intracellular signaling and function by caveolin.
AB  - Caveolae, flask-like invaginations of the plasma membrane, were discovered nearly
      60 years ago. Originally regarded as fixation artifacts of electron microscopy,
      the functional role for these structures has taken decades to unravel. The
      discovery of the caveolin protein in 1992 (by the late Richard G.W. Anderson)
      accelerated progress in defining the contribution of caveolae to cellular
      physiology and pathophysiology. The three isoforms of caveolin (caveolin-1, -2,
      and -3) are caveolae-resident structural and scaffolding proteins that are
      critical for the formation of caveolae and their localization of signaling
      entities. A PubMed search for "caveolae" reveals ~280 publications from their
      discovery in the 1950s to the early 1990s, whereas a search for "caveolae or
      caveolin" after 1990, identifies ~7000 entries. Most work on the regulation of
      biological responses by caveolae and caveolin since 1990 has focused on caveolae
      as plasma membrane microdomains and the function of caveolin proteins at the
      plasma membrane. By contrast, our recent work and that of others has explored the
      localization of caveolins in multiple cellular membrane compartments and in the
      regulation of intracellular signaling. Cellular organelles that contain caveolin
      include mitochondria, nuclei and the endoplasmic reticulum. Such intracellular
      localization allows for a complexity of responses to extracellular stimuli by
      caveolin and the possibility of novel organelle-targeted therapeutics. This
      review focuses on the impact of intracellular localization of caveolin on signal
      transduction and cell regulation.

PMID- 24858279
TI  - Lamin B1 overexpression increases nuclear rigidity in autosomal dominant
      leukodystrophy fibroblasts.
AB  - The architecture and structural mechanics of the cell nucleus are defined by the
      nuclear lamina, which is formed by A- and B-type lamins. Recently, gene
      duplication and protein overexpression of lamin B1 (LB1) have been reported in
      pedigrees with autosomal dominant leukodystrophy (ADLD). However, how the
      overexpression of LB1 affects nuclear mechanics and function and how it may
      result in pathology remain unexplored. Here, we report that in primary human skin
      fibroblasts derived from ADLD patients, LB1, but not other lamins, is
      overexpressed at the nuclear lamina and specifically enhances nuclear stiffness.
      Transient transfection of LB1 in HEK293 and neuronal N2a cells mimics the
      mechanical phenotype of ADLD nuclei. Notably, in ADLD fibroblasts, reducing LB1
      protein levels by shRNA knockdown restores elasticity values to those
      indistinguishable from control fibroblasts. Moreover, isolated nuclei from ADLD
      fibroblasts display a reduced nuclear ion channel open probability on voltage
      step application, suggesting that biophysical changes induced by LB1
      overexpression may alter nuclear signaling cascades in somatic cells. Overall,
      the overexpression of LB1 in ADLD cells alters nuclear mechanics and is linked to
      changes in nuclear signaling, which could help explain the pathogenesis of this
      disease.

PMID- 24858281
TI  - DNA methylation abnormalities at gene promoters are extensive and variable in the
      elderly and phenocopy cancer cells.
AB  - Abnormal patterns of DNA methylation are one of the hallmarks of cancer cells.
      The process of aging has also been associated with similar, albeit less dramatic,
      changes in methylation patterns, leading to the hypothesis that age-related
      changes in DNA methylation may partially underlie the increased risk of cancer in
      the elderly. Here we studied 377 participants aged 85 yr from the Newcastle 85+
      Study to investigate the extent of, and interindividual variation in, age-related
      changes in DNA methylation at specific CpG islands. Using highly quantitative
      pyrosequencing analysis, we found extensive and highly variable methylation of
      promoter-associated CpG islands with levels ranging from 4% to 35%, even at known
      tumor suppressor genes such as TWIST2. Furthermore, the interindividual
      differences in methylation seen across this elderly population phenocopies
      multiple features of the altered methylation patterns seen in cancer cells. Both
      aging- and cancer-related methylation can occur at similar sets of genes, both
      result in the formation of densely methylated, and likely transcriptionally
      repressed, alleles, and both exhibit coordinate methylation across multiple loci.
      In addition, high methylation levels were associated with subsequent diagnosis of
      leukemia or lymphoma during a 3-yr follow-up period (P=0.00008). These data
      suggest that the accumulation of age-related changes in promoter-associated CpG
      islands may contribute to the increased cancer risk seen during aging.-Gautrey,
      H. E., van Otterdijk, S. D., Cordell, H. J., Newcastle 85+ study core team,
      Mathers, J. C., Strathdee, G. DNA methylation abnormalities at gene promoters are
      extensive and variable in the elderly and phenocopy cancer cells. 

PMID- 24858280
TI  - The WNT signaling antagonist Dickkopf-1 directs lineage commitment and promotes
      survival of the preimplantation embryo.
AB  - Successful embryonic development is dependent on factors secreted by the
      reproductive tract. Dickkopf-1 (DKK1), an antagonist of the wingless-related
      mouse mammary tumor virus (WNT) signaling pathway, is one endometrial secretory
      protein potentially involved in maternal-embryo communication. The purpose of
      this study was to investigate the roles of DKK1 in embryo cell fate decisions and
      competence to establish pregnancy. Using in vitro-produced bovine embryos, we
      demonstrate that exposure of embryos to DKK1 during the period of morula to
      blastocyst transition (between d 5 and 8 of development) promotes the first 2
      cell fate decisions leading to increased differentiation of cells toward the
      trophectoderm and hypoblast lineages compared with that for control embryos
      treated with vehicle. Moreover, treatment of embryos with DKK1 or colony
      stimulating factor 2 (CSF2; an endometrial cytokine known to improve embryo
      development and pregnancy establishment) between d 5 and 7 of development
      improves embryo survival after transfer to recipients. Pregnancy success at d 32
      of gestation was 27% for cows receiving control embryos treated with vehicle, 41%
      for cows receiving embryos treated with DKK1, and 39% for cows receiving embryos
      treated with CSF2. These novel findings represent the first evidence of a role
      for maternally derived WNT regulators during this period and could lead to
      improvements in assisted reproductive technologies.

PMID- 24858282
TI  - Associations between ozone, PM2.5, and four pollen types on emergency department
      pediatric asthma events during the warm season in New Jersey: a case-crossover
      study.
AB  - BACKGROUND: Asthma is one of the most common chronic diseases among school-aged
      children in the United States. Environmental respiratory irritants exacerbate
      asthma among children. Understanding the impact of a variety of known and
      biologically plausible environmental irritants and triggers among children in New
      Jersey - ozone, fine particulate matter (PM2.5), tree pollen, weed pollen, grass
      pollen and ragweed - would allow for informed public health interventions.
      METHODS: Time-stratified case-crossover design was used to study the transient
      impact of ozone, PM2.5 and pollen on the acute onset of pediatric asthma. Daily
      emergency department visits were obtained for children aged 3-17 years with a
      primary diagnosis of asthma during the warm season (April through September),
      2004-2007 (inclusive). Bi-directional control sampling was used to select two
      control periods for each case for a total of 65,562 inclusion days. Since the
      period of exposure prior to emergency department visit may be the most clinically
      relevant, lag exposures were investigated (same day (lag0), 1, 2, 3, 4, and 5 as
      well as 3-day and 5-day moving averages). Multivariable conditional logistic
      regression controlling for holiday, school-in-session indicator, and 3-day moving
      average for temperature and relative humidity was used to examine the
      associations. Odds ratios are based on interquartile range (IQR) increases or 10
      unit increases when IQR ranges were narrow. Single-pollutant models as well as
      multipollutant models were examined. Stratification on gender, race, ethnicity
      and socioeconomic status was explored. RESULTS: The associations with ozone and
      PM2.5 were strongest on the same day (lag0) of the emergency department visit (RR
      IQR=1.05, 95% CI 1.04-1.06) and (RR IQR=1.03, 95% CI 1.02-1.04), respectively,
      with a decreasing lag effect. Tree and weed pollen were associated with pediatric
      ED visits; the largest magnitudes of association was with the 5-day average (RR
      IQR=1.23, 95% CI 1.21-1.25) and (RR 10=1.13, 95% CI 1.12-1.14), respectively.
      Grass pollen was only minimally associated with the outcome while ragweed had a
      negative association. CONCLUSIONS: The ambient air pollutant ozone is associated
      with increases in pediatric emergency department asthma visits during the warm
      weather season. The different pollen types showed different associations with the
      outcome. High levels of tree pollen appear to be an important risk factor in
      asthma exacerbations.

PMID- 24858283
TI  - A microcosm approach to evaluate the degradation of tributyltin (TBT) by
      Aeromonas molluscorum Av27 in estuarine sediments.
AB  - Tributyltin (TBT) is a biocide extremely toxic to a wide range of organisms,
      which has been used for decades in antifouling paints. Despite its global ban in
      2008, TBT is still a problem of great concern due to the high levels trapped in
      sediments. Aeromonas molluscorum Av27 is a TBT degrading bacterium that was
      isolated from an estuarine system. We investigated the ability and the role of
      this bacterium on TBT degradation in this estuarine system, using a microcosm
      approach in order to mimic environmental conditions. The experiment was
      established and followed for 150 days. Simultaneously, changes in the indigenous
      bacterial community structure were also investigated. The results revealed a
      maximum TBT degradation rate of 28% accompanied by the detection of the
      degradation products over time. Additionally, it was observed that TBT
      degradation was significantly enhanced by the presence of Av27. In addition a
      significantly higher TBT degradation occurred when the concentration of Av27 was
      higher. TBT degradation affected the bacterial community composition as revealed
      by the changes in the prevalence of Proteobacteria subdivisions, namely the
      increase of Deltaproteobacteria and the onset of Epsilonproteobacteria. However,
      the addition of Av27 strain did not affect the dominant phylotypes. Total
      bacterial number, bacterial biomass productivity, 16S rRNA gene and denaturing
      gradient gel electrophoresis (DGGE) analyses also indicated alterations on the
      bacterial community structure over time, with bacteria non-tolerant to pollutants
      increasing their representativeness, as, for instance, the increase of the number
      of Alphaproteobacteria clones from 6% in the beginning to 12% at the end of the
      experiment. The work herein presented confirms the potential of Av27 strain to be
      used in the decontamination of TBT-polluted environments. 

PMID- 24858284
TI  - Mobilisation of lipophilic pollutants from blubber in northern elephant seal pups
      (Mirounga angustirostris) during the post-weaning fast.
AB  - Northern elephant seals (NES) (Mirounga angustirostris) from the Ano Nuevo State
      Reserve (CA, USA) were longitudinally sampled during the post-weaning fast in
      order to study the mobilisation and redistribution of various classes of
      persistent organic pollutants (POPs), such as polybrominated diphenyl ethers
      (PBDEs), polychlorinated biphenyls (PCBs), dichlorodiphenyldichloroethylene (p,p'
      DDE) and hexachlorobenzene (HCB) between blubber and blood. Inner and outer
      blubber layers were analysed separately. Organohalogenated compounds were
      detected in all blubber samples in the decreasing order of their concentrations:
      p,p'-DDE > PCBs ? HCB > PBDEs. The concentrations of all studied compounds were
      homogeneously distributed in the blubber layer at early fast, since the
      concentrations of POPs were statistically not different in the inner and outer
      layers. With the progression of the fast, the concentrations of PBDEs, PCBs and
      p,p'-DDE increased more sharply in inner blubber than in outer blubber. As a
      result, their levels became significantly higher in inner blubber as compared to
      outer blubber at late fast. The rise of pollutant concentrations in blubber might
      result from a less efficient mobilisation than triglycerides and/or a reuptake by
      adipocytes of some of the pollutants released into the circulation. The
      mobilisation of pollutants from blubber was higher at late fast. An increase of
      pollutant concentrations was observed in serum between early and late fast. Lower
      halogenated congeners (i.e. tetra-CBs) were present in higher proportions in
      serum, whereas the higher halogenated congeners (i.e. hepta-CBs) were mainly
      found in the inner and outer blubber layers. The transfer ratios of both PBDEs
      and PCBs from inner blubber to serum decreased with the number of chlorine and
      bromine atoms. In addition, the distribution of both types of compounds between
      serum and blubber was strongly influenced by their lipophilic character (logKow
      values), with more lipophilic compounds being less efficiently released from
      blubber to serum.

PMID- 24858285
TI  - Effects of proton pump inhibitors on lung cancer precise radiotherapy-induced
      radiation pneumonitis.
AB  - The objective of this study was to explore the effects of proton pump inhibitors
      (PPIs) on the development and prognosis of lung cancer precise radiotherapy
      induced radiation pneumonitis. Clinical materials of 84 lung cancer patients who
      had radiation pneumonitis after precise radiotherapy were retrospectively
      analyzed, and the patients were divided into PPI group and control group,
      according to whether or not PPIs were applied. The development and prognosis of
      patients and the effects of different doses of PPI on patient condition from two
      groups were compared. There were 57 PPI cases in PPI group and 27 cases in
      control group. Basic characteristics of patients were not statistically different
      between the two groups; however, white blood cell count, oxygenation indexes,
      blood gas pH, and lung imaging index were significantly different (p < 0.05),
      indicating that radiation pneumonitis tended to be more severe in PPI group. As
      regards effects of PPI on prognosis of two groups, remission rate of radiation
      pneumonia in PPI group was significantly less than that of the control group.
      Among 57 cases in PPI group, there were 31 patients applied with PPI <= 1DDD and
      31 patients applied with PPI > 1DDD. In comparison of the various parameters of
      patients, 7 days after being applied with different doses of PPI, there were no
      significant differences between the parameters of radiation pneumonitis. PPIs
      should be cautiously utilized to avoid the effects of lung cancer radiotherapy
      induced radiation pneumonia.

PMID- 24858287
TI  - Mechanism for temperature-dependent production of piscicolin 126.
AB  - Piscicolin 126 is a class 2a bacteriocin produced by Carnobacterium
      maltaromaticum strains UAL26 and JG126. Whilst strain UAL26 shows temperature
      dependent piscicolin 126 production, strain JG126 produces bacteriocin at any
      growth temperature. Several clones containing combinations of the ATP-binding
      cassette transporter (pisT) and transporter accessory (pisE) genes from JG126 and
      UAL26 were created and tested for bacteriocin production. Bacteriocin production
      at 25  degrees C was observed only for a clone containing both pisT and pisE from
      JG126 (U-T(J)E(J)) and a clone containing pisT from UAL26 and pisE from JG126 (U
      BamT(U)E(J)). Therefore, the deletion of a single CG base pair located on pisE of
      UAL26 that results in a frameshift and truncation of PisE causes the temperature
      dependent piscicolin 126 production. Bacteriocin production of UAL26 was induced
      at 25  degrees C by the addition of supernatant containing the autoinducer
      peptide (AIP); however, the antimicrobial activity was lost after two subsequent
      overnight cultivations due to the presumed lack of the AIP. Changes in membrane
      fluidity due to changes in temperature or the presence of 2-phenylethanol (PHE)
      affected bacteriocin production of UAL26, but not of clones U-T(J)E(J) or U
      BamT(U)E(J). Similarly, increased membrane fluidity due to PHE addition reduced
      production of sakacin A in Lactobacillus sakei Lb706 and Lactobacillus curvatus
      LTH 1174. The mechanism involved in the temperature-dependent piscicolin 126
      production was described. Due to the conformational change in PisE at 25  degrees
      C, the transport machinery was not able to translocate AIP. To the best of our
      knowledge, this is the first report that links membrane fluidity with the
      regulation of bacteriocin production. 

PMID- 24858286
TI  - Biochemical characterization of the major N-acetylmuramidase from Lactobacillus
      buchneri.
AB  - Bacterial cell wall hydrolases are essential for peptidoglycan remodelling in
      regard to bacterial cell growth and division. In this study, peptidoglycan
      hydrolases (PGHs) of different Lactobacillus buchneri strains were investigated.
      First, the genome sequence of L. buchneri CD034 and L. buchneri NRRL B-30929 was
      analysed in silico for the presence of PGHs. Of 23 putative PGHs with different
      predicted hydrolytic specificities, the glycosyl hydrolase family 25 domain
      containing homologues LbGH25B and LbGH25N from L. buchneri CD034 and NRRL B
      30929, respectively, were selected and characterized in detail. Zymogram analysis
      confirmed hydrolysing activity on bacterial cell walls for both enzymes.
      Subsequent reversed-phase HPLC and MALDI-TOF MS analysis of the peptidoglycan
      breakdown products from L. buchneri strains CD034 and NRRL B-30929, and from
      Lactobacillus rhamnosus GG, which served as a reference, revealed that LbGH25B
      and LbGH25N have N-acetylmuramidase activity. Both enzymes were identified as
      cell wall-associated proteins by means of immunofluorescence microscopy and
      cellular fractionation, as well as by the ability of purified recombinant LbGH25B
      and LbGH25N to bind to L. buchneri cell walls in vitro. Moreover, similar
      secondary structures mainly composed of beta-sheets and nearly identical thermal
      stabilities with Tm values around 49  degrees C were found for the two N
      acetylmuramidases by far-UV circular dichroism spectroscopy. The functional and
      structural data obtained are discussed and compared to related PGHs. In this
      study, a major N-acetylmuramidase from L. buchneri was characterized in detail
      for the first time. 

PMID- 24858288
TI  - [Effect on treatment planning based on properties of cobalt-60 stereotactic
      radiosurgery units].
AB  - The brand-new version of gamma knife, Perfexion, is equipped with an automatic
      collimator arrangement system that does not require manual collimator exchange
      and a couch-traveling system that is approximately ten times faster than Model C,
      so treatment time with multiple shots is assumed to remain within a clinically
      acceptable range. In this study, the treatment plans for Model C and Perfexion
      were compared from the viewpoint of number of shots, coverage, selectivity,
      conformity, and gradient in planning target volume (PTV) coverage. We enrolled
      187 and 89 patients with vestibular schwannomas treated by Model C and Perfexion
      in the study. Treatment planning was created on a Leksell GammaPlan workstation.
      The mean PTV was 5.2 ml (range 0.1-18.4 ml) in Model C and 4.1 ml (range 0.1-32.1
      ml) in Perfexion. The mean shot number for Model C and Perfexion was 11 (range 2
      27) and 16 (range 1-41) at the isodose contour of 40-60%, respectively. The mean
      PTV coverage was 94% (range 73-100%) and 98% (range 91-100%), and the mean PTV
      selectivity was 83% (range 46-98%) and 87% (range 63-97%) for Model C and
      Perfexion, respectively. The mean conformity index was 1.15 (range 0.81-2.02) and
      1.14 (range 0.97-1.57), and the mean gradient index was 2.82 (range 2.37-3.35)
      and 2.91 (range 2.55-4.48) for Model C and Perfexion, respectively. In Perfexion,
      better PTV coverage and selectivity were achieved by using an excessively large
      number of shots. In addition, the use of a small collimator in Perfexion produced
      a steeper dose gradient. Our comparative research demonstrated the greater
      clinical usefulness of Perfexion. 

PMID- 24858289
TI  - [Radiation dose evaluation in a photon-counting digital mammography unit].
AB  - The purpose of our study was to evaluate radiation dose and beam quality in
      photon-counting digital mammography (PCDM) and compare them with those in a full
      field digital mammography (FFDM) unit. Dose variation in the X-ray tube axis
      direction, aluminum half-value layer, average glandular and skin doses, and
      contrast-to-noise ratio (CNR) were evaluated for the PCDM and FFDM units. In
      PCDM, the dose variation in the X-ray tube axis direction was greater than that
      in FFDM. At a tube voltage of 28 kV, the first half-value layers were 0.407 mmAl
      for PCDM, 0.357 mmAl for FFDM with a molybdenum target and molybdenum filter
      (Mo/Mo), and 0.579 mmAl for FFDM with a tungsten target and rhodium filter
      (W/Rh). The average glandular doses with 45-mm-equivalent breast thickness were
      0.723 mGy for the PCDM, 1.55 mGy for the FFDM with Mo/Mo in low-dose mode, and
      0.835 mGy for the FFDM with W/Rh in low-dose mode. In PCDM, the skin dose was
      equivalent to or lower than that in FFDM. The CNR was 2.65+/-0.04, 2.35+/-0.04,
      and 2.52+/-0.03 for the PCDM, FFDM with Mo/Mo, and that with W/Rh, respectively.
      The CNR for PCDM was significantly higher than that for FFDM (p<0.001). It is
      therefore possible to reduce the radiation dose to the patient by using a PCDM
      unit while maintaining a significantly higher CNR than with the FFDM unit. 

PMID- 24858290
TI  - [A comparison of several convenient methods of estimating effective energy in X
      ray computed tomography].
AB  - The measurement of half-value layers (HVLs) and effective energy in X-ray
      computed tomography (CT) using conventional nonrotating methods is regarded as a
      highly challenging task, as it necessitates the use of a nonrotating X-ray tube
      and the assistance of service engineers. Several convenient methods have been
      proposed to circumvent this limitation; however, to the best of our knowledge,
      there are no reports that provide a comparative study on the accuracy of each
      method. This prompted us to compare the accuracy and practicality of each method.
      Effective energy was calculated using four methods: lead shielding, copper pipe,
      localization, and inner-metal center-air ratio (IMCAR). The accuracy of each
      method for the measurement of effective energy in X-ray CT was evaluated and
      compared with the conventional nonrotating method. The differences in the
      effective energy were 0.0 to 0.6 keV (0.0% to 1.1%) for lead shielding, -2.2 to 
      0.6 keV (1.4% to 4.3%) for copper pipe, 4.7 to 16.7 keV (9.9% to 31.4%) for
      localization, and -7.4 to -0.3 keV (0.6% to 17.5%) for the IMCAR method. The
      results indicate that the lead shielding method is the most accurate and
      practical method of estimating effective energy in X-ray CT. 

PMID- 24858291
TI  - [Usefulness of spatially adaptive noise reduction processing in computer-assisted
      diagnosis system for bone scintigraphy].
AB  - OBJECTIVES: The goal of this study was to assess the diagnostic accuracy of Pixon
      processed images in comparison with raw images for computer-assisted
      interpretation of bone scintigraphy (BONENAVI). METHODS: Whole-body scans of 57
      patients with prostate cancer who had undergone bone scintigraphy for suspected
      bone metastases were obtained approximately 3 h after intravenous injection of
      740 MBq (99m)Tc-methylene diphosphonate. We obtained two image sets: raw images
      and images processed using the Pixon method. Artificial neural network (ANN)
      values, bone scan index (BSI), number of hotspots and regional ANN value of two
      images set were automatically calculated by the BONENAVI software. Areas under
      the receiver operator characteristic curves (AUC) were calculated in patient
      based and lesion-based analyses. RESULTS: In ten cases with bone metastases, ANN,
      BSI and number of hotspots for processed images were equivalent to those in the
      raw images. However, in 47 cases without bone metastases, ANN, BSI and number of
      hotspots for processed images showed significantly lower values than those for
      the raw images (p<0.05). Sensitivity, specificity and accuracy of the raw images
      were 90.2, 44.7 and 65.9%, and those of the processed images were 90.2, 57.4 and
      72.7%, respectively. The AUC for processed images was equivalent to that for raw
      images. CONCLUSIONS: Specificity and accuracy in the detection of bone metastases
      showed the Pixon-processed images to have high diagnostic performance. We
      conclude that the precision of computer-assisted interpretation of bone
      scintigraphy can be enhanced by using Pixon processing.

PMID- 24858292
TI  - [Use of surgical clips to verify positional accuracy in image-guided accelerated
      partial breast irradiation].
AB  - The purpose of this study was to evaluate the accuracy of positional verification
      during overall radiation treatment periods in accelerated partial breast
      irradiation using one or more surgical clips. We first investigated the
      appropriate computed tomography (CT) slice thickness and detectability of clips
      for a matching criterion in a phantom study. Next, clinical investigations were
      carried on 12 patients with multiple clips positioned around the lumpectomy
      cavity. During radiation treatment planning, a 5-mm region of interest (5-mm ROI)
      was defined by adding a three dimentional (3D) margin of 5 mm to each clip.
      During treatment, the clips on two orthogonal kilovoltage X-ray images acquired
      were moved so as to be included in the corresponding 5-mm ROI on digitally
      reconstructed radiographs (DRRs). Positional accuracy was calculated using the
      displacement of each clip in the verification images. The displacements of each
      clip acquired in all setups were then calculated throughout the overall radiation
      treatment period and the factors affecting the displacement of clips were
      investigated. Positional accuracy was also investigated in setups using skin
      marks and in setups using the bone structure around the thorax. We demonstrated
      in a phantom study that a CT slice thickness of 2.5 mm was appropriate. In our
      clinical investigations, 91% of the clips were included in the 5-mm ROI. The
      interfractional displacement of clips was large, with a long distance between the
      isocenter and each clip at the time of radiation treatment planning. 

PMID- 24858293
TI  - [The control of respiratory organ motion in the field of radiology: the viewpoint
      of a radiation oncologist].

PMID- 24858296
TI  - [Globalization Committee Report].

PMID- 24858294
TI  - [Past, present, and future of the catheter room].

PMID- 24858297
TI  - [Overview of new" pharmaceutical and medical device affairs law"].

PMID- 24858298
TI  - [Radiological sciences and technology for radiological technologists].

PMID- 24858299
TI  - The protease activity of transthyretin reverses the effect of pH on the amyloid
      beta protein/heparan sulfate proteoglycan interaction: a biochromatographic
      study.
AB  - Patients suffering of Alzheimer's disease (AD) are characterized by a low
      transthyretin (TTR) level in the brain. The effect of pH and TTR concentration in
      the medium on the beta-amyloid protein (Abeta)/heparan sulfate proteoglycan
      (HSPG) association mechanism were studied using a biochromatographic approach.
      For this purpose, HSPG was immobilized via amino groups onto the amino propyl
      silica pre-packed column, activated with glutaraldehyde, by using the Schiff base
      method. Using an equilibrium perturbation method, it was clearly shown that Abeta
      can be bound with HSPG. This approach allowed the determination of the
      thermodynamic data of this binding mechanism. The role of the pH was also
      analyzed. Results from enthalpy-entropy compensation and the plot of the number
      of protons exchanged versus pH showed that the binding mechanism was dependent on
      pH with a critical value at pH=6.5. This value agreed with a histidine
      protonation as an imidazolium cation. Moreover, the corresponding thermodynamical
      data showed that at pH>6.5, van der Waals and hydrogen bonds due to aromatic
      amino acids as tyrosine or phenylalanine present in the N-terminal (NT) part
      governed the Abeta/HSPG association. Abeta remained in its physiological
      structure in a random coil form (i.e. the non-amyloidogenic structure) because
      van der Waals interactions and hydrogen bonds were preponderant. At acidic pH
      (pH<6.5), ionic and hydrophobic interactions, created by histidine protonation
      and hydrophobic amino acids, appeared in the Abeta/HSPG binding. These
      hydrophobic and ionic interactions led to the conversion of the random coil form
      of Abeta into a beta-sheet structure which was the amyloidogenic folding. When
      TTR was incubated with Abeta, the Abeta/HSPG association mechanism was enthalpy
      driven at all pH values. The affinity of Abeta for HSPG decreased when TTR
      concentration increased due to the complexation of Abeta with TTR. Also, the
      decrease of the peak area with the increase of TTR concentration demonstrated
      that this Abeta/TTR association led to the cleavage of Abeta full length to a
      smaller fragment. For acidic pH (pH<6.5), it was shown that the importance of the
      hydrophobic and ionic interactions decreased when TTR concentration increased.
      This result confirmed that Abeta was cleaved by TTR in a part containing only the
      NT part. Our results demonstrated clearly that TTR reversed the effect of acidic
      pH and thus played a protective role in AD. 

PMID- 24858300
TI  - Isolation and structure characterization of related impurities in etimicin
      intermediate P1 by LC/ESI-MS(n) and NMR.
AB  - Etimicin intermediate 3,2",6"-N,N,N-triacetyl gentamicin C1a (P1), is a key
      intermediate of etimicin, which is a semi-synthetic aminoglycoside antibiotic
      effective to both gram-positive and gram-negative bacteria infections. Four major
      related impurities of P1 were detected by HPLC-ELSD and ESI-MS(n) methods. Weakly
      acidic cation exchange resin, CM-sephadex and silica gel column chromatography
      were used for the isolation and purification of four major impurities. By means
      of ESI-MS(n) and NMR analysis, related impurities were characterized as 3,2"-N,N
      diacetyl gentamicin C1a (1), 3,2",6"-N,N,N-triacetyl gentamicin C2b (2), 2"-N
      acetyl gentamicin C1a (3), and 2",6"-N,N-diacetyl gentamicin C1a (4). Impurities
      1, 2, 4 are novel compounds and the NMR data of these isolates were first
      reported in this paper. The possible mechanism for the formation of these
      impurities is also discussed. 

PMID- 24858301
TI  - Sorbitol-modified hyaluronic acid reduces oxidative stress, apoptosis and
      mediators of inflammation and catabolism in human osteoarthritic chondrocytes.
AB  - OBJECTIVE AND DESIGN: Our study was designed to elucidate the precise molecular
      mechanisms by which sorbitol-modified hyaluronic acid (HA/sorbitol) exerts
      beneficial effects in osteoarthritis (OA). METHODS: Human OA chondrocytes were
      treated with increasing doses of HA/sorbitol +/- anti-CD44 antibody or with
      sorbitol alone and thereafter with or without interleukin-1beta (IL-1beta) or
      hydrogen peroxide (H2O2). Signal transduction pathways and parameters related to
      oxidative stress, apoptosis, inflammation, and catabolism were investigated.
      RESULTS: HA/sorbitol prevented IL-1beta-induced oxidative stress, as measured by
      reactive oxygen species, p47-NADPH oxidase phosphorylation, 4-hydroxynonenal
      (HNE) production and HNE-metabolizing glutathione-S-transferase A4-4 expression.
      Moreover, HA/sorbitol stifled IL-1beta-induced metalloproteinase-13, nitric oxide
      (NO) and prostaglandin E2 release as well as inducible NO synthase expression.
      Study of the apoptosis process revealed that this gel significantly attenuated
      cell death, caspase-3 activation and DNA fragmentation elicited by exposure to a
      cytotoxic H2O2 dose. Examination of signaling pathway components disclosed that
      HA/sorbitol prevented IL-1beta-induced p38 mitogen-activated protein kinase and
      nuclear factor-kappa B activation, but not that of extracellular signal-regulated
      kinases 1 and 2. Interestingly, the antioxidant as well as the anti-inflammatory
      and anti-catabolic effects of HA/sorbitol were attributed to sorbitol and HA,
      respectively. CONCLUSIONS: Altogether, our findings support a beneficial effect
      of HA/sorbitol in OA through the restoration of redox status and reduction of
      apoptosis, inflammation and catabolism involved in cartilage damage.

PMID- 24858302
TI  - Involvement of COX2-thromboxane pathway in TCDD-induced precardiac edema in
      developing zebrafish.
AB  - The cardiovascular system is one of the most characteristic and important targets
      for developmental toxicity by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in fish
      larvae. However, knowledge of the mechanism of TCDD-induced edema after
      heterodimerization of aryl hydrocarbon receptor type 2 (AHR2) and AHR nuclear
      translocator type 1 (ARNT1) is still limited. In the present study, microscopic
      analysis with a high-speed camera revealed that TCDD increased the size of a
      small cavity between the heart and body wall in early eleutheroembryos, a toxic
      effect that we designate as precardiac edema. A concentration-response curve for
      precardiac edema at 2 days post fertilization (dpf) showed close similarity to
      that for conventional pericardial edema at 3 dpf. Precardiac edema caused by TCDD
      was reduced by morpholino knockdown of AHR2 and ARNT1, as well as by an
      antioxidant (ascorbic acid). A selective inhibitor of cyclooxygenase type 2
      (COX2), NS398, also markedly inhibited TCDD-induced precardiac edema. A
      thromboxane receptor (TP) antagonist, ICI-192,605 almost abolished TCDD-induced
      precardiac edema and this effect was canceled by U46619, a TP agonist, which was
      not influential in the action of TCDD by itself. Knockdown of COX2b and
      thromboxane A synthase 1 (TBXS), but not COX2a, strongly reduced TCDD-induced
      precardiac edema. Knockdown of COX2b was without effect on mesencephalic
      circulation failure caused by TCDD. The edema by TCDD was also inhibited by
      knockdown of c-mpl, a thrombopoietin receptor necessary for thromobocyte
      production. Finally, induction of COX2b, but not COX2a, by TCDD was seen in
      eleutheroembryos at 3 dpf. These results suggest a role of the COX2b-thromboxane
      pathway in precardiac edema formation following TCDD exposure in developing
      zebrafish.

PMID- 24858303
TI  - Vulvodynia: Current state of the biological science.

PMID- 24858304
TI  - Multivitamin restriction increases adiposity and disrupts glucose homeostasis in
      mice.
AB  - A strong association between obesity and low plasma concentrations of vitamins
      has been widely reported; however, the causality of this relationship is still
      not established. Our goal was to evaluate the impact of a multivitamin
      restriction diet (MRD) on body weight, adiposity and glucose homeostasis in mice.
      The mice were given a standard diet or a diet containing 50 % of the recommended
      vitamin intake (MRD) for 12 weeks. At the end of the experiment, total body
      weight was 6 % higher in MRD animals than in the control group, and the adiposity
      of the MRD animals more than doubled. The HOMA-IR index of the MRD animals was
      significantly increased. The adipose tissue of MRD animals had lower expression
      of mRNA encoding adiponectin and Pnpla2 (47 and 32 %, respectively) and 43 %
      higher leptin mRNA levels. In the liver, the mRNA levels of Pparalpha and
      Pgc1alpha were reduced (29 and 69 %, respectively) in MRD mice. Finally, the
      level of beta-hydroxybutyrate, a ketonic body reflecting fatty acid oxidation,
      was decreased by 45 % in MRD mice. Our results suggest that MRD promotes
      adiposity, possibly by decreasing adipose tissue lipolysis and hepatic beta
      oxidation. These results could highlight a possible role of vitamin deficiency in
      the etiology of obesity and associated disorders. 

PMID- 24858305
TI  - Dietary capsaicin ameliorates pressure overload-induced cardiac hypertrophy and
      fibrosis through the transient receptor potential vanilloid type 1.
AB  - BACKGROUND: Dietary capsaicin plays a protective role in hypertension,
      atherosclerosis, obesity, and hyperlipidemia through activating the transient
      receptor potential vanilloid type 1 (TRPV1), a nonselective cation channel. This
      study was designed to investigate the role of capsaicin in cardiac hypertrophy
      and fibrosis in a pressure overload model. METHODS: TRPV1 knockout (KO) mice and
      their wild-type (WT) littermates, aged 8 weeks, were randomly divided into sham
      and aortic banding surgery groups and were fed with chow or chow plus capsaicin
      for 10 weeks. RESULTS: Dietary capsaicin significantly attenuates pressure
      overload-induced increase in heart weight index, enlargement of ventricular
      volume, decrease in cardiac function, and increase in cardiac fibrosis in WT
      mice. However, these effects of capsaicin were absent in TRPV1 KO mice.
      Additionally, capsaicin blunted pressure overload-induced upregulation of
      transforming growth factor beta, connective tissue growth factor, and the
      phosphorylation of Smad2/3 in WT mice but not in TRPV1 KO mice. Moreover,
      capsaicin attenuated pressure overload-induced overexpression of
      metalloproteinase (MMP)-2, MMP-9 and MMP-13 in WT mice but not in TRPV1 KO mice.
      Capsaicin also attenuated angiotensin II-induced proliferation of cardiac
      fibroblasts from mice with the TRPV1 channel. CONCLUSIONS: Our results suggest
      that dietary capsaicin protects against cardiac hypertrophy and fibrosis in
      pressure overload mice through TRPV1.

PMID- 24858306
TI  - Association between retinal vessel caliber and arterial stiffness in a population
      comprised of normotensive to early-stage hypertensive individuals.
AB  - BACKGROUND: Although impairment of the micro- and macrocirculation is considered
      inherent to sustained hypertension, there is a substantial lack of studies
      investigating whether an association exists between micro- and macrovascular
      damage, especially in early-stage hypertension. METHODS: We studied a
      meticulously selected population, free of diabetes and cardiovascular disease, of
      223 individuals: 137 never-treated, newly diagnosed patients with recent onset of
      hypertension and 86 normotensive individuals. Nonmydriatic retinal photography
      was used to assess retinal microvascular diameters, including central retinal
      arteriolar (CRAE) and venular equivalent and arteriovenous ratio (AVR). Arterial
      stiffness was evaluated by measurement of pulse wave velocity (PWV) and aortic
      augmentation index (AIx). RESULTS: Compared with normotensive subjects,
      hypertensive patients exhibited significantly increased PWV (8.1 vs. 7.1 m/sec; P
      < 0.001) and AIx (23.86% vs. 18.8%; P = 0.01) and decreased CRAE (86.47 vs. 91.44
      MUm; P = 0.001) and AVR (0.74 vs. 0.78; P = 0.007). A significant inverse
      association was demonstrated between PWV and CRAE (r = -0.205; P = 0.002), which
      remained significant after multivariable analysis. Likewise, CRAE (P = 0.04) and
      AVR (P = 0.02) were independent predictors of AIx. CONCLUSIONS: This study shows
      for the first time an association between quantitatively assessed retinal
      abnormalities and increased arterial stiffness in a sample of early-stage
      hypertensive and normotensive individuals, suggesting that micro- and
      macrocirculation impairment in hypertension is a dynamic, mutual, interdependent
      process present from its very early stages. Given the predictive value of both
      retinal arteriolar narrowing and arterial stiffness in terms of cardiovascular
      mortality and morbidity, identification of combined micro- and macrovascular
      damage might be helpful in cardiovascular risk stratification of hypertensive
      patients.

PMID- 24858307
TI  - Comparative proteomic analyses provide new insights into low phosphorus stress
      responses in maize leaves.
AB  - Phosphorus deficiency limits plant growth and development. To better understand
      the mechanisms behind how maize responds to phosphate stress, we compared the
      proteome analysis results of two groups of maize leaves that were treated
      separately with 1,000 uM (control, +P) and 5 uM of KH2PO4 (intervention group, 
      P) for 25 days. In total, 1,342 protein spots were detected on 2-DE maps and
      15.43% had changed (P<0.05; >=1.5-fold) significantly in quantity between the +P
      and -P groups. These proteins are involved in several major metabolic pathways,
      including photosynthesis, carbohydrate metabolism, energy metabolism, secondary
      metabolism, signal transduction, protein synthesis, cell rescue and cell defense
      and virulence. The results showed that the reduction in photosynthesis under low
      phosphorus treatment was due to the down-regulation of the proteins involved in
      CO2 enrichment, the Calvin cycle and the electron transport system. Electron
      transport and photosynthesis restrictions resulted in a large accumulation of
      peroxides. Maize has developed many different reactive oxygen species (ROS)
      scavenging mechanisms to cope with low phosphorus stress, including up-regulating
      its antioxidant content and antioxidase activity. After being subjected to
      phosphorus stress over a long period, maize may increase its internal phosphorus
      utilization efficiency by altering photorespiration, starch synthesis and lipid
      composition. These results provide important information about how maize responds
      to low phosphorus stress. 

PMID- 24858308
TI  - Comparison of partial volume effects in arterial and venous contrast curves in CT
      brain perfusion imaging.
AB  - PURPOSE: In brain CT perfusion (CTP), the arterial contrast bolus is scaled to
      have the same area under the curve (AUC) as the venous outflow to correct for
      partial volume effects (PVE). This scaling is based on the assumption that large
      veins are unaffected by PVE. Measurement of the internal carotid artery (ICA),
      usually unaffected by PVE due to its large diameter, may avoid the need for
      partial volume correction. The aims of this work are to examine i) the
      assumptions behind PVE correction and ii) the potential of selecting the ICA
      obviating correction for PVE. METHODS: The AUC of the ICA and sagittal sinus were
      measured in CTP datasets from 52 patients. The AUCs were determined by i) using
      commercial CTP software based on a Gaussian curve-fitting to the time attenuation
      curve, and ii) by simple integration of the time attenuation curve over a time
      interval. In addition, frames acquired up to 3 minutes after first bolus passage
      were used to examine the ratio of arterial and venous enhancement. The impact of
      selecting the ICA without PVE correction was illustrated by reporting cerebral
      blood volume (CBV) measurements. RESULTS: In 49 of 52 patients, the AUC of the
      ICA was significantly larger than that of the sagittal sinus (p = 0.017).
      Measured after the first pass bolus, contrast enhancement remained 50% higher in
      the ICA just after the first pass bolus, and 30% higher 3 minutes later. CBV
      measurements were significantly lowered when the ICA was used without PVE
      correction. CONCLUSIONS: Contradicting the assumptions underlying PVE correction,
      contrast in the ICA was significantly higher than in the sagittal sinus, even 3
      minutes after the first pass of the contrast bolus. PVE correction might lead to
      overestimation of CBV if the CBV is calculated using the AUC of the time
      attenuation curves.

PMID- 24858309
TI  - Search asymmetry and eye movements in infants and adults.
AB  - Search asymmetry is characterized by the detection of a feature-present target
      amidst feature-absent distractors being efficient and unaffected by the number of
      distractors, whereas detection of a feature-absent target amidst feature-present
      distractors is typically inefficient and affected by the number of distractors.
      Although studies have attempted to investigate this phenomenon with infants
      (e.g., Adler, Inslicht, Rovee-Collier, & Gerhardstein in Infant Behavioral
      Development, 21, 253-272, 1998; Colombo, Mitchell, Coldren, & Atwater in Journal
      of Experimental Psychology: Learning, Memory and Cognition, 19, 98-109, 1990),
      due to methodological limitations, their findings have been unable to
      definitively establish the development of visual search mechanisms in infants.
      The present study assessed eye movements as a means to examine an asymmetry in
      responding to feature-present versus feature-absent targets in 3-month-olds,
      relative to adults. Saccade latencies to localize a target (or a distractor, as
      in the homogeneous conditions) were measured as infants and adults randomly
      viewed feature-present (R among Ps), feature-absent (P among Rs), and homogeneous
      (either all Rs or all Ps) arrays at set sizes of 1, 3, 5, and 8. Results
      indicated that neither infants' nor adults' saccade latencies to localize the
      target in the feature-present arrays were affected by increasing set sizes,
      suggesting that localization of the target was efficient. In contrast, saccade
      latencies to localize the target in the feature-absent arrays increased with
      increasing set sizes for both infants and adults, suggesting an inefficient
      localization. These findings indicate that infants exhibit an asymmetry
      consistent with that found with adults, providing support for functional bottom
      up selective attention mechanisms in early infancy. 

PMID- 24858310
TI  - Diterpene synthases and their responsible cyclic natural products.
AB  - This review provides an overview of diterpene synthases which were initially
      identified via genetic and/or biochemical means, traversing all organisms
      researched to date. 

PMID- 24858311
TI  - Identification of DW532 as a novel anti-tumor agent targeting both kinases and
      tubulin.
AB  - AIM: 7,8-Dihydroxy-4-(3-hydroxy-4-methoxyphenyl)-2H-chromen-2-one (DW532) is one
      of simplified analogues of hematoxylin that has shown broad-spectrum inhibition
      on tyrosine kinases and in vitro anti-cancer activities. The aim of this study
      was to identify DW532 as a agent targeting both kinases and tubulin, and to
      investigate its anti-cancer and anti-angiogenesis activities. METHODS: In vitro
      tyrosine kinases activity was examined with ELISA, and tyrosine kinases activity
      in cells was evaluated with Western blot analysis. Tubulin turbidity assay,
      surface plasmon resonance and immunofluorescence technique were used to
      characterize the tubulin inhibitory activity. Cell proliferation was examined
      with SRB assay, and cell apoptosis and cell cycle distribution were analyzed with
      Annexin-V/PI staining and flow cytometry. Tube formation, aortic ring and chick
      chorioallantoic membrane assays were used to evaluate the anti-angiogenesis
      efficacy. RESULTS: DW532 inhibited EGFR and VEGFR2 in vitro kinase activity (the
      IC50 values were 4.9 and 5.5 MUmol/L, respectively), and suppressed their
      downstream signaling. DW532 dose-dependently inhibited tubulin polymerization via
      direct binding to tubulin, thus disrupting the mitotic spindle assembly and
      leading to abnormal cell division. In a panel of human cancer cells, DW532 (1 and
      10 MUmol/L) induced G2/M phase arrest and cell apoptosis, which subsequently
      resulted in cytotoxicity. Knockdown of BubR1 or Mps1, the two core proteins of
      the spindle assembly checkpoint dramatically decreased DW532-induced cell cycle
      arrest in MDA-MB-468 cells. Moreover, treatment with DW532 potently and dose
      dependently suppressed angiogenesis in vitro and in vivo. CONCLUSION: DW532 is a
      dual inhibitor against tubulin and tyrosine kinases, and deserves further
      development as a novel anti-cancer agent.

PMID- 24858312
TI  - Potassium 2-(1-hydroxypentyl)-benzoate promotes long-term potentiation in Abeta1
      42-injected rats and APP/PS1 transgenic mice.
AB  - AIM: Potassium 2-(1-hydroxypentyl)-benzoate (dl-PHPB) is a new drug candidate for
      ischemic stroke. The aim of this study was to investigate the effects of dl-PHPB
      on memory deficits and long-term potentiation (LTP) impairment in animal models
      of Alzheimer's disease. METHODS: The expression of NMDA receptor subunits GluN1
      and GluN2B in the hippocampus and cortex of APP/PS1 transgenic mice were detected
      using Western blot analysis. Memory deficits of the mice were evaluated with the
      passive avoidance test. LTP impairment was studied in the dentate region of
      Abeta1-42-injected rats and APP/PS1 transgenic mice. RESULTS: APP/PS1 transgenic
      mice showed significantly lower levels of GluN1 and p-GluN2B in hippocampus, and
      chronic administration of dl-PHPB (100 mg . kg(-1) . d(-1), po) reversed the
      downregulation of p-GluN2B, but did not change GluN1 level in the hippocampus.
      Furthermore, chronic administration of dl-PHPB reversed the memory deficits in
      APP/PS1 transgenic mice. In the dentate region of normal rats, injection of dl
      PHPB (100 MUmol/L, icv) did not change the basal synaptic transmission, but
      significantly enhanced the high-frequency stimulation (HFS)-induced LTP, which
      was completely prevented by pre-injection of APV (150 MUmol/L, icv). Chronic
      administration of dl-PHPB (100 mg . kg(-1) . d(-1), po) reversed LTP impairment
      in Abeta1-42-injected normal rats and APP/PS1 transgenic mice. CONCLUSION:
      Chronic administration of dl-PHPB improves learning and memory and promotes LTP
      in the animal models of Alzheimer's disease, possibly via increasing p-GluN2B
      expression in the hippocampus.

PMID- 24858313
TI  - Effects of SKF83959 on the excitability of hippocampal CA1 pyramidal neurons: a
      modeling study.
AB  - AIM: 3-Methyl-6-chloro-7,8-hydroxy-1-(3-methylphenyl)-2,3,4,5-tetrahydro-1H-3
      benzazepine (SKF83959) have been shown to affect several types of voltage
      dependent channels in hippocampal pyramidal neurons. The aim of this study was to
      determine how modulation of a individual type of the channels by SKF83959
      contributes to the overall excitability of CA1 pyramidal neurons during either
      direct current injections or synaptic activation. METHODS: Rat hippocampal slices
      were prepared. The kinetics of voltage-dependent Na(+) channels and neuronal
      excitability and depolarization block in CA1 pyramidal neurons were examined
      using whole-cell recording. A realistic mathematical model of hippocampal CA1
      pyramidal neuron was used to simulate the effects of SKF83959 on neuronal
      excitability. RESULTS: SKF83959 (50 MUmol/L) shifted the inactivation curve of
      Na(+) current by 10.3 mV but had no effect on the activation curve in CA1
      pyramidal neurons. The effects of SKF83959 on passive membrane properties,
      including a decreased input resistance and depolarized resting potential,
      predicted by our simulations were in agreement with the experimental data. The
      simulations showed that decreased excitability of the soma by SKF83959 (examined
      with current injection at the soma) was only observed when the membrane potential
      was compensated to the control levels, whereas the decreased dendritic
      excitability (examined with current injection at the dendrite) was found even
      without membrane potential compensation, which led to a decreased number of
      action potentials initiated at the soma. Moreover, SKF83959 significantly
      facilitated depolarization block in CA1 pyramidal neurons. SKF83959 decreased
      EPSP temporal summation and, of physiologically greater relevance, the synaptic
      driven firing frequency. CONCLUSION: SKF83959 decreased the excitability of CA1
      pyramidal neurons even though the drug caused the membrane potential
      depolarization. The results may reveal a partial mechanism for the drug's anti
      Parkinsonian effects and may also suggest that SKF83959 has a potential
      antiepileptic effect.

PMID- 24858314
TI  - Carbon nanotubes leading the way forward in new generation 3D tissue engineering.
AB  - Statistics from the NHS Blood and Transplant Annual Review show that total organ
      transplants have increased to 4213 in 2012, while the number of people waiting to
      receive an organ rose to 7613 that same year. Human donors as the origin of
      transplanted organs no longer meet the ever-increasing demand, and so interest
      has shifted to synthetic organ genesis as a form of supply. This focus has given
      rise to new generation tissue and organ engineering, in the hope of one day
      designing 3D organs in vitro. While research in this field has been conducted for
      several decades, leading to the first synthetic trachea transplant in 2011,
      scaffold design for optimising complex tissue growth is still underexplored and
      underdeveloped. This is mostly the result of the complexity required in
      scaffolds, as they need to mimic the cells' native extracellular matrix. This is
      an intricate nanostructured environment that provides cells with physical and
      chemical stimuli for optimum cell attachment, proliferation and differentiation.
      Carbon nanotubes are a popular addition to synthetic scaffolds and have already
      begun to revolutionise regenerative medicine. Discovered in 1991, these are
      traditionally used in various areas of engineering and technology; however, due
      to their excellent mechanical, chemical and electrical properties their potential
      is now being explored in areas of drug delivery, in vivo biosensor application
      and tissue engineering. The incorporation of CNTs into polymer scaffolds displays
      a variety of structural and chemical enhancements, some of which include:
      increased scaffold strength and flexibility, improved biocompatibility, reduction
      in cancerous cell division, induction of angiogenesis, reduced thrombosis, and
      manipulation of gene expression in developing cells. Moreover CNTs' tensile
      properties open doors for dynamic scaffold design, while their thermal and
      electrical properties provide opportunities for the development of neural, bone
      and cardiac tissue constructs. This review will provide an update on the use of
      CNTs in 3D organ generation. 

PMID- 24858315
TI  - Global unbalance in seaweed production, research effort and biotechnology
      markets.
AB  - Exploitation of the world's oceans is rapidly growing as evidenced by a booming
      patent market of marine products including seaweed, a resource that is easily
      accessible without sophisticated bioprospecting technology and that has a high
      level of domestication globally. The investment in research effort on seaweed
      aquaculture has recently been identified to be the main force for the development
      of a biotechnology market of seaweed-derived products and is a more important
      driver than the capacity of seaweed production. Here, we examined seaweed patent
      registrations between 1980 and 2009 to assess the growth rate of seaweed
      biotechnology, its geographic distribution and the types of applications
      patented. We compare this growth with scientific investment in seaweed
      aquaculture and with the market of seaweed production. We found that both the
      seaweed patenting market and the rate of scientific publications are rapidly
      growing (11% and 16.8% per year respectively) since 1990. The patent market is
      highly geographically skewed (95% of all registrations belonging to ten countries
      and the top two holding 65% of the total) compared to the distribution of
      scientific output among countries (60% of all scientific publications belonging
      to ten countries and the top two countries holding a 21%), but more homogeneously
      distributed than the production market (with a 99.8% belonging to the top ten
      countries, and a 71% to the top two). Food industry was the dominant application
      for both the patent registrations (37.7%) and the scientific publications (21%)
      followed in both cases by agriculture and aquaculture applications. This result
      is consistent with the seaweed taxa most represented. Kelp, which was the target
      taxa for 47% of the patent registrations, is a traditional ingredient in Asian
      food and Gracilaria and Ulva, which were the focus of 15% and 13% of the
      scientific publications respectively, that are also used in more sophisticated
      applications such as cosmetics, chemical industry or bioremediation. Our analyses
      indicate a recent interest of non-seaweed producing countries to play a part in
      the seaweed patenting market focusing on more sophisticated products, while
      developing countries still have a limited share in this booming market. We
      suggest that this trend could be reverted by promoting partnerships for R and D
      to connect on-going efforts in aquaculture production with the emerging
      opportunities for new biotech applications of seaweed products. 

PMID- 24858316
TI  - The impact of antenatal testing for advanced maternal age on cesarean delivery
      rate at an urban institution.
AB  - OBJECTIVE: Antenatal testing has been implemented for advanced maternal age (AMA)
      women given their increased stillbirth risk. Our objective was to evaluate
      cesarean delivery and induction rates after the start of antenatal testing at our
      institution. STUDY DESIGN: A retrospective cohort study of AMA women (>= 40
      years) who delivered at our institution was performed. Testing for AMA began in
      2005. AMA women who delivered before (unexposed) and after (exposed) the
      implementation were compared. Our primary outcome was cesarean delivery and
      secondary outcome was induction. Chi-square compared categorical variables and
      multivariable logistic regression calculated odds ratio (OR) and controlled for
      confounders. RESULTS: A total of 276 women were included (147 unexposed and 129
      exposed). The cesarean rate was higher in the exposed group (53 vs. 39%, OR 1.76
      [1.09-2.84]). The increased risk of cesarean remained after adjusting for race,
      previous cesarean, multiple gestations, and parity (adjusted OR 1.85 [1.05
      3.28]). When excluding those with previous cesareans, the risk of primary
      cesarean was not significant (OR 1.57 [0.89-2.76]). The induction rate was not
      different (38 vs. 33%, p = 0.4). CONCLUSIONS: While overall cesareans increased,
      there was no difference in primary cesarean and induction rates for AMA women
      after implementation of antenatal testing for AMA.

PMID- 24858317
TI  - Twin anemia-polycythemia sequence in monochorionic twins: implications for
      diagnosis and treatment.
AB  - Twin anemia-polycythemia sequence (TAPS) is a recently described complication of
      monochorionic placentation characterized by discordance in hemoglobin (Hgb)
      levels in the absence of amniotic fluid abnormality characteristic of classical
      twin-twin transfusion syndrome (TTTS). The placental angioarchitecture that
      predisposes to TAPS consists of small diameter arteriovenous anastomoses and the
      absence of balancing arterioarterial anastomoses. This vascular pattern occurs
      sporadically in 3 to 5% of monochorionic twins or iatrogenically following 2 to
      13% of selective fetoscopic laser surgeries for TTTS. The diagnosis is based on
      measurement of the middle cerebral artery peak systolic velocity (MCA-PSV) which
      is not part of the Quintero staging for TTTS. With mild disease increased MCA-PSV
      in the anemic donor twin and a decreased MCA-PSV in the recipient twin are
      characteristic while severe disease is associated with critical Doppler findings,
      hydrops or single twin demise as in TTTS. Treatment options include fetoscopic
      laser, fetal blood transfusion, conservative management, and often preterm
      delivery. The most promising approach to TAPS is its prevention since the
      iatrogenic form comprises the majority of cases. When the fetoscopic laser
      technique is modified by coagulating the chorionic plate along the vascular
      equator (equatorial dichorionization or "Solomon" technique) the incidence of
      postlaser TAPS and recurrent TTTS is significantly reduced, survival is improved,
      and there is no increase in complications. 

PMID- 24858318
TI  - Twin-to-twin transfusion syndrome: prenatal diagnosis and treatment.
AB  - CLINICAL PROBLEM: Twin-to-twin transfusion syndrome (TTTS) increases perinatal
      morbidity and mortality for 10 to 15% of monochorionic (MC) gestations.
      PATHOPHYSIOLOGY: MC gestations are at risk due to the angioarchitecture of the
      shared placenta, with anastomoses of varying type, size, and quantity. TTTS
      results from progression of a chronic perfusion imbalance across unbalanced
      placental anastomoses, typically arising between 15 and 26 weeks gestation. The
      resulting abnormal fetal blood volume levels and compensatory physiological
      responses lead to an increased risk for fetal death, end-organ damage, and
      preterm birth. PRENATAL DIAGNOSIS: Surveillance with ultrasound is essential for
      detection and treatment. TTTS is diagnosed once polyhydramnios occurs in the
      recipient (maximal vertical fluid pocket [MVP] > 8 cm) and oligohydramnios in the
      donor (MVP < 2 cm). The Quintero et al method is commonly used for staging,
      utilizing the presence or absence of donor bladder filling, abnormal fetal
      Doppler values, fetal hydrops, and demise. TREATMENT: Fetoscopic laser
      photocoagulation of placental anastomoses is an effective treatment addressing
      the underlying pathophysiology. Further research is needed to improve survival
      rates, reduce risks of fetoscopy, and gain understanding of the prediction,
      assessment, and optimization of long-term outcomes for TTTS survivors.

PMID- 24858319
TI  - The problem of preterm delivery after laser surgery.
AB  - Preterm birth after fetoscopic laser surgery for twin-twin transfusion continues
      to be a major challenge despite improved survival rates. The risk factors for the
      complications have been identified, which include preterm premature rupture of
      membranes, cervical length shortening, larger cannula diameter, amnioinfusion,
      complicated procedure, and severe disease. The interventions to prevent preterm
      birth such as cervical cerclage for short cervix and collagen plug placement have
      not been successful. Further understanding of the pathophysiology is urgently
      needed to identify newer methods to prevent preterm birth. 

PMID- 24858321
TI  - Antagonistic mechanisms of synbiosis between Lactobacillus plantarum CIF17AN2 and
      green banana starch in the proximal colon model challenged with Salmonella
      Typhimurium.
AB  - Antagonistic mechanisms of Lactobacillus plantarum CIF17AN2 (an infant isolate),
      saba starch, and their synbiotic combination against Salmonella Typhimurium
      SA2093 were evaluated. The anti-Salmonella activity was investigated under the
      competitive niche of fecal microbiota using the simulated proximal colon model.
      The alterations of the dominant fecal microbiota and beneficial bacteria were
      also displayed using FISH and PCR-DGGE techniques. L. plantarum CIF17AN2
      exhibited anti-Salmonella mechanisms through secretion of antimicrobial
      compounds, adhesion ability and competitive adhesion to mucin and HT-29 cell
      line. However, the Salmonella inhibition was significantly reduced in the
      presence of human fecal microflora. The combination of saba starch with L.
      plantarum CIF17AN2 showed the greatest inhibition against Sal. Typhimurium SA2093
      in the simulated colon model. The enhancement of anti-Salmonella activity due to
      the addition of saba starch corresponded to a significant decrease in pH and an
      increase of lactic acid and short chain fatty acids. According to PCR-DGGE
      analysis, L. plantarum CIF17AN2 was able to survive and effectively compete with
      fecal microflora. Saba starch supplement modified bifidobacterial profile but had
      a slight impact on the profile of lactic acid bacteria. This prebiotic approach
      alleviated the nutrient limitation in the proximal colon model leading to the
      selective stimulation of beneficial lactobacilli and bifidobacteria, hence the
      enhancement of anti-Salmonella activity. 

PMID- 24858320
TI  - Diagnosis and treatment of fetal arrhythmia.
AB  - AIMS: Detection and careful stratification of fetal heart rate (FHR) is extremely
      important in all pregnancies. The most lethal cardiac rhythm disturbances occur
      during apparently normal pregnancies where FHR and rhythm are regular and within
      normal or low-normal ranges. These hidden depolarization and repolarization
      abnormalities, associated with genetic ion channelopathies cannot be detected by
      echocardiography, and may be responsible for up to 10% of unexplained fetal
      demise, prompting a need for newer and better fetal diagnostic techniques. Other
      manifest fetal arrhythmias such as premature beats, tachycardia, and bradycardia
      are commonly recognized. METHODS: Heart rhythm diagnosis in obstetrical practice
      is usually made by M-mode and pulsed Doppler fetal echocardiography, but not all
      fetal cardiac time intervals are captured by echocardiographic methods. RESULTS
      AND CONCLUSIONS: This article reviews different types of fetal arrhythmias, their
      presentation and treatment strategies, and gives an overview of the present and
      future diagnostic techniques.

PMID- 24858322
TI  - Dissemination of patient navigation programs across the United States.
AB  - OBJECTIVE: To use diffusion and dissemination frameworks to describe how
      indicators of economic and health care disparity affect the location and type of
      patient navigation programs. METHODS: A cross-sectional national Web-based survey
      conducted during 2009-2010 with support from 65 separate national and regional
      stakeholder organizations. PARTICIPANTS: A total of 1116 self-identified patient
      navigators across the United States. MAIN OUTCOME MEASURE: The location and
      characteristics of patient navigation programs according to economic and health
      care disparity indicators. RESULTS: Patient navigation programs appear to be
      geographically dispersed across the United States. Program differences were
      observed in navigator type, population served, and setting by poverty level.
      Programs in high-poverty versus low-poverty areas were more likely to use lay
      navigators (P < .001) and to be located in community health centers and agencies
      with religious affiliations (50.6 vs 36.4%, and 21.5% vs 16.7%. respectively; P
      <= 0.01). CONCLUSION(S): Results suggest that navigation programs have spread
      beyond initial target inception areas and also serve as a potentially important
      resource in communities with higher levels of poverty and/or relatively low
      access to care. In addition, while nurse navigators have emerged as a significant
      component of the patient navigation workforce, lay health navigators serve a
      vital role in underserved communities. Other factors from dissemination
      frameworks may influence the spread of navigation and provide useful insights to
      support the dissemination of programs to areas of high need.

PMID- 24858324
TI  - Rebuttal: 'Obesity hypoventilation syndrome (OHS): does the current definition
      need revisiting?'.

PMID- 24858323
TI  - A comprehensive professional development training's effect on afterschool program
      staff behaviors to promote healthy eating and physical activity.
AB  - OBJECTIVE: Evaluate a comprehensive intervention designed to support staff and
      program leaders in the implementation of the YMCA of USA healthy eating and
      physical activity (HEPA) standards for their afterschool programs (3-6 pm).
      DESIGN: Pre- (fall 2011) and postassessment (spring 2012) no-control group.
      SETTING/PARTICIPANTS: Four large-scale YMCA afterschool programs serving
      approximately 500 children. INTERVENTION: Professional development training
      founded on the 5Ms (ie, Mission, Model, Manage, Monitor, and Maximize) and LET US
      Play principles (ie, Lines, Elimination, Team size, Uninvolved staff/kids, and
      Space, equipment, and rules), on-site booster training sessions, workshops, and
      ongoing technical support for staff and program leaders from January to May 2012.
      MAIN OUTCOME MEASURES: System for Observing Staff Promotion of Activity and
      Nutrition. ANALYSIS: Multilevel mixed-effects linear (ie, staff behaviors
      expressed as a percentage of the number of scans observed) and logistic
      regression. RESULTS: A total of 5328 System for Observing Staff Promotion of
      Activity and Nutrition scans were completed over the 2 measurement periods. Of
      the 20 staff behaviors identified in HEPA standards and measured in this study,
      17 increased or decreased in the appropriate direction. For example, the
      proportion staff engaged in physical activity with children increased from 26.6%
      to 37% and the proportion of staff eating unhealthy foods decreased from 42.1% to
      4.5%. CONCLUSIONS: Comprehensive professional development training, founded on
      the 5Ms and LET US Play principles, and ongoing technical assistance can have a
      sizable impact on key staff behaviors identified by HEPA standards for
      afterschool programs.

PMID- 24858325
TI  - Quality of corrosion specimens prepared from material obtained during autopsies -
      a preliminary study.
AB  - AIM: Aim of this study was to assess the quality of the corrosion specimens
      obtained during autopsies of human body for scanning electron microscopy
      procedures. MATERIALS AND METHOD: Ninety seven uteri were obtained upon autopsy
      of women aged 25-56 years, deceased due to causes not related to disorders of the
      reproductive system. Fourty three of them contained large subserosal uterine
      leiomyomata. twenty uteri were injected with acrylic emulsion Liquitex R via the
      arteries or veins. Five of these uteri were next dissected and cut into slides on
      a microtom. the remaining uteri were injected with 60-80 ml of mercox CL-2r
      resin, next macerated and studied under scanning electron microscope (JEOL SEM 35
      CF scanning electron microscope at 20-25 kV). RESULTS: Best human specimens were
      obtained from the autopsies carried out possibly early after the deceased, young
      aged (between 25 and 45) and died because of multitrauma not associated with the
      pelvic injury. CONCLUSIONS: Specimens obtained from autopsies can be used for
      scanning electron microscopy however under several conditions, specially the time
      between death and undertaking the injection procedures and the age of the
      individual, because of the process of artherosclerosis.

PMID- 24858326
TI  - Coronary artery abnormalities in Kawasaki disease.
AB  - INTRODUCTION: Kawasaki disease is the number one cause of acquired heart disease
      among children in developed countries. AIM: The aim of the study was a
      retrospective analysis of the factors that may influence the persistence of
      coronary artery abnormalities in patients with Kawasaki disease. MATERIALS AND
      METHODS: Analyzing the medical records of patients hospitalized in the University
      Children's Hospital of Krakow in the years 2005-2011 we collected the data of 28
      patients diagnosed with Kawasaki disease. The group was divided into two
      subgroups, depending on the duration of the persistence of changes in the
      coronary arteries - A (n = 17) for up to 6 months, B (n = 11) - for more than 6
      months. Both groups were analyzed for the presence of factors that may influence
      the course of the disease. RESULTS: There were more boys in group A (11 boys
      (65%), 6 girls (35%)), whereas in group B the distribution was more uniform (6
      boys (55%), 5 girls (45%)). The age of onset in group A was 37.9 months (SD
      30.8), in group B 39.5 months (SD 16.7). 17.6% of patients in group A and 36.4%
      in group B were treated with glucocorticoids. CONCLUSIONS: In the group of
      patients in which coronary artery abnormalities disappeared more quickly, male
      and slightly older children dominated. The only difference observed between the 2
      groups related to the frequency of the use of glucocorticoids, they were used
      more often in children, in whom coronary artery abnormalities persisted longer.

PMID- 24858327
TI  - Vascular structure of outer myometrial uterine leiomyomata - a preliminary SEM
      and immunohistochemical study.
AB  - AIM: The main goal of this study was assessment of vascular structure of uterine
      leiomyomata localized between outer myometrium and endometrium. MATERIALS AND
      METHODS: The study was carried out on thirty two human uteri collected upon
      autopsy. Vessels were injected with synthetic resin, next corroded and coated
      with gold, finally observed using scanning electron microscope. Next ten uteri
      were injected with acrylic emulsion and studies using immunohistochemical
      staining for von Willebrandt's factor. RESULTS: Vascular structure of outer
      myometrial leiomyomata was quite similar to those observed in the middle of
      muscular layer of uterus, characterized by relatively dense 'vascular capsule',
      consisted of flattened vein, arterioles and capillaries. CONCLUSIONS: Structure
      of outer myometrial uterine leiomyomata was similar to those observed during
      growth within myometrium.

PMID- 24858328
TI  - Assessment of angiotensin I metabolism in the human placenta using an LC/MS
      method.
AB  - The local renin-angiotensin system (RAS) in the placenta plays a very important
      role in placental development. It is well known that during normal pregnancy most
      of the circulating and local RAS components are over-expressed and any disruption
      of this new balance may cause pregnancy complications. The aim of this study was
      to assess the metabolism of Ang I in placentas from normal pregnancy, in an ex
      vivo model, using an LC/MS method. The obtained results suggest that placental
      tissue is able to produce many angiotensin peptides but the main metabolite is
      Ang-(1-7). 

PMID- 24858329
TI  - Clinical importance of the middle meningeal artery.
AB  - Middle meningeal artery (MMA)is an important branch which supplies among others
      cranial dura mater. It directly attaches to the cranial bones (is incorporated
      into periosteal layer of dura mater), favors common injuries in course of head
      trauma. This review describes available data on the MMA considering its
      varability, or treats specific diseases or injuries where the course of MMA may
      have clinical impact. 

PMID- 24858330
TI  - Empathy level differences between Polish surgeons and physicians.
AB  - AIM: The aim of this study was to assess the levels of empathy among Polish
      physicians and surgeons. MATERIALS AND METHODS: Ninety-two physicians took part
      in the study. The physicians were either employed in hospitals, outpatient
      clinics or university departments in Krakow. The participants were asked to fill
      out a personal questionnaire, the Emotional Empathy Scale (EES), as well as
      describe four chosen tables from the Thematic Apperception Test (TAT). RESULTS:
      The study group consisted of 92 physicians, including 25 women (27.2%) and 67
      men, in the mean age of 42 +/- 16.3 years (age span: 27-68 years). The physicians
      have been divided into two subgroups - non-surgical specialists (52 people -
      56.5%) and surgical specialists (40 people - 43.5%). There were no gender
      differences, as to the level of empathy, in the study group (p >0.05). Non
      surgical specialists displayed a higher level of empathy (p=0.03) than their
      surgical counterparts. There was a positive correlation between age and the level
      of empathy. This was seen both among non-surgical (r = 0.41; p < 0.0001) and
      surgical specialists (r = 0.59; p < 0.0001). No correlation was seen between the
      number of years of experience working as a doctor and the level of empathy (p >
      0.05). CONCLUSIONS: Empathy is an essential element in the physician-patient
      relationship. This study has shown that non-surgical specialists display a higher
      level of empathy. We have also shown that years of experience working as a doctor
      do not influence the level of empathy, while age is a beneficial factor.

PMID- 24858331
TI  - Preliminary psychometric validation of the Polish version of the EORTC head and
      neck module (QLQ-H&N35).
AB  - AIM: The aim of our study was to report preliminary validation data on the EORTC
      translated, Polish version of the EORTC QLQ-H&N35 questionnaire to show that this
      tool is an acceptable and psychometrically robust measure to collect HRQoL data
      in Polish patients with head and neck malignancies. MATERIALS AND METHODS:
      Patients with histological confirmation of head and neck malignancies were
      eligible for the study. All patients filled out the Polish version of the EORTC
      QLQ-H&N35 module in addition to EORTC QLQ-C30 and a demographic questionnaire.
      Standardized validity and reliability analyses were performed. RESULTS: Fifty-one
      patients (23 females - 45.1%) were enrolled into the study, with a mean age of
      51.3 +/- 12.9 years. Cronbach alpha coefficients, range 0.72-0.85, showed
      positive internal consistency. Satisfactory convergent and discriminant validity
      in multi-trait scaling analyses was seen. CONCLUSIONS: Basing on the preliminary
      data from this report, one can say that the Polish version of the EORTC QLQ-H&N35
      module is a reliable and valid tool for measuring HRQoL in patients with head and
      neck malignancies. However further research is needed to establish the full
      psychometric properties of the described module, especially test-retest and
      responsiveness over time.

PMID- 24858332
TI  - Visual feedback training using WII Fit improves balance in Parkinson's disease.
AB  - Postural instability including imbalance is the most disabling long term problem
      in Parkinson's disease (PD) that does not respond to pharmacotherapy. This study
      aimed at investigating the effectiveness of a novel visual-feedback training
      method, using Wii Fit balance board in improving balance in patients with PD.
      Twenty four patients with moderate PD were included in the study which comprised
      of a 6-week home-based balance training program using Nintendo Wii Fit and
      balance board. The PD patients significantly improved their results in Berg
      Balance Scale, Tinnet's Performance-Oriented Mobility Assessment, Timed Up-and
      Go, Sit-to-stand test, 10-Meter Walk test and Activities-specific Balance
      Confidence scale at the end of the programme. This study suggests that visual
      feedback training using Wii-Fit with balance board could improve dynamic and
      functional balance as well as motor disability in PD patients.

PMID- 24858333
TI  - Anatomy of the pterygomandibular space - clinical implication and review.
AB  - AIM: The aim of this study was to present review of the pterygomandibular space
      with some referrals to clinical practice, specially to the methods of lower teeth
      anesthesia. CONCLUSIONS: Pterygomandibular space is a clinically important region
      which is commonly missing in anatomical textbooks. More attention should be paid
      to it both from theoretical and practical point of view, especially in teaching
      the students of first year of dental studies.

PMID- 24858334
TI  - Determination of hepatocyte growth factor at early phase of acute pancreatitis.
AB  - AIM: The aim of this study was to assess the diagnostic value of hepatocyte
      growth factor (HGF) as a new predictor of severity in patients with acute
      pancreatitis (AP) at early phase of disease. MATERIALS AND METHOD: The studied
      group involved 40 patients (16 women and 24 men) with AP admitted to Ist Dept. of
      Surgery Jagiellonian University Medical College in Krakow. Twenty-four patients
      had mild and twelve severe form of AP. Glasgow and Imrie scores were calculated
      to evaluate severity of AP. HGF concentrations were measured by ELISA (R&D
      Systems) on days 1, 3 and 5 after admission within 48 hours after onset of
      symptoms. RESULTS: Serum median concentrations of HGF was significantly higher in
      patients with severe versus mild clinical course of AP on each of the study days
      (7.61 vs 3.30 ng/mL, p = 0.05 on day 1; 7.19 vs 3.43, p = 0.04 on day 3 and 5.76
      vs 2.42, p = 0.02 on day 5). HGF positively correlated with Glasgow and Imrie
      scores (R = 0.57 and R = 0.51). HGF negatively correlated with fetuin A, a
      negative acute phase protein (R = -0.60 on day 3 and R = -0.45 on day 5) and
      positively with CRP (R = 0.93; R = 0.80), SAA (R = 0.78; R = 0.82), IL-6 (R =
      0.61; R = 0.77; R = 0.85 on day 1, 3 and 5, respectively) and PMN-elastase (R =
      0.58; R = 0.64; R = 0.77). On day 1 of the study, HGF reached the diagnostic
      sensitivity of 100% and specificity of 50% for the detection of severe and
      moderate AP. CONCLUSIONS: Serum HGF correlates with several inflammatory markers
      and clinical scores (Glasgow, Imrie) in patients with AP and may be considered a
      new promising tool in assessing the severity of acute pancreatitis.

PMID- 24858335
TI  - Diabetes and Quality of Life: Initial Approach to Depression, Physical Activity,
      and Sexual Dysfunction.
AB  - The different aspects that contribute to quality of life in patients with
      diabetes mellitus, such as mood, are of great importance for the treatment of
      this disease. These aspects not only influence the well-being of patients but
      also influence treatment adherence, therefore affecting the course of the
      disease. A panel of experts from Argentina, Chile, and Uruguay performed a review
      of the main aspects affecting quality of life in patients with diabetes: physical
      activity, mood disorders, and sexual activity. The consensus of the panel was
      that physical activity is important in the treatment of patients with diabetes
      because it reduces morbidity, mortality, and disease complications, and it should
      be performed on a regular basis, bearing in mind the patient's characteristics.
      Increased physical activity is associated with better glycemic control, and in
      individuals with glucose intolerance, it delays progression toward diabetes. In
      patients with diabetes, there is a high prevalence of depression, which can
      influence treatment adherence. Therefore, early detection of depression is
      essential to improve the course of diabetes. Regarding sexual activity, erectile
      dysfunction may be a significant sign in the case of suspected diabetes and the
      early diagnosis of vasculopathy in patients with diabetes. In conclusion, greater
      emphasis should be placed on improving patient knowledge, early detection, and
      multidisciplinary approaches to deal with the aspects of diabetes that affect
      patients' quality of life. 

PMID- 24858336
TI  - Fecal Transplant for Treatment of Toxic Megacolon Associated With Clostridium
      Difficile Colitis in a Patient With Duchenne Muscular Dystrophy.
AB  - Clostridium difficile (C diff) colitis infection is the most common cause of
      nosocomial infectious diarrhea and the prevalence is increasing worldwide. Toxic
      megacolon is a severe complication of C diff colitis associated with high
      mortality. Gastrointestinal (GI) comorbidity and impaired smooth muscle
      contraction are risk factors for the development of C diff-associated toxic
      megacolon. We present a case of fulminant C diff colitis with toxic megacolon in
      a patient with Duchenne muscular dystrophy (DMD) in the intensive care unit. C
      diff colitis was diagnosed by clinical presentation and positive C diff DNA
      amplification test (polymerase chain reaction). The impairment of GI tract due to
      DMD predisposes these patients to severe C diff infection and toxic megacolon, as
      observed in this case report. For the same reason, the recovery of GI function in
      these patients can be prolonged. While surgery was conducted for relieving the
      pressure from toxic megacolon, fecal microbiota transplantation through
      colonoscopy resulted in successful resolution of the C diff symptoms, although
      the recovery is prolonged due to DMD. 

PMID- 24858337
TI  - Synthesis and investigation of biological properties of modified 6-oxa-estra
      1,3,5(10),8(9)-tetraenes.
AB  - To investigate the relationship between structure and biological activity of
      analogues of steroid estrogens we have developed the synthesis of 7alpha-methyl-6
      oxa-estra-1,3,5(10),8(9)-tetraenes with cis- and trans-junction of C and D rings.
      We found that such compounds have stronger osteoprotective, cholesterol-lowering
      and antioxidant properties in comparison with uterotrophic activity; that is the
      advantage in comparison with clinically used 17alpha-ethynylestradiol. 

PMID- 24858338
TI  - Vascular neuropeptide Y contributes to atherosclerotic plaque progression and
      perivascular mast cell activation.
AB  - AIM: Neuropeptide Y is an abundantly expressed neurotransmitter capable of
      modulating both immune and metabolic responses related to the development of
      atherosclerosis. NPY receptors are expressed by a number of vascular wall cell
      types, among which mast cells. However, the direct effects of NPY on
      atherosclerotic plaque development and progression remain to be investigated. In
      this study we thus aimed to determine whether NPY is expressed in atherosclerotic
      plaques and to establish its role in atherosclerotic plaque development. METHODS
      AND RESULTS: NPY expression was seen to be increased up to 2-fold in unstable
      human endarterectomy plaques, as compared to stable plaques, and to be
      significantly upregulated during lesion progression in apoE(-/-) mice. In apoE(-/
      ) mice focal overexpression of NPY in the carotid artery significantly increased
      atherosclerotic plaque size compared to controls, while plaque composition was
      unaffected. Interestingly, perivascular mast cell activation was significantly
      higher in the NPY-overexpressing mice, suggesting that NPY may impact plaque
      progression in part via mast cell activation. Furthermore, in vitro NPY-induced
      murine mast cell activation resulted in the release of pro-atherogenic mediators
      including IL-6 and tryptase. CONCLUSIONS: Our data show that NPY expression is
      increased during atherogenesis and in particular in unstable plaques.
      Furthermore, perivascular overexpression of NPY promoted plaque development and
      perivascular mast cell activation, suggestive of a role for NPY-induced mast cell
      activation in lesion progression.

PMID- 24858339
TI  - Influence of apolipoprotein E, age and aortic site on calcium phosphate induced
      abdominal aortic aneurysm in mice.
AB  - OBJECTIVE: To assess relevant features of abdominal aortic aneurysms (AAA)
      induced by calcium phosphate within a mouse model. Specifically we investigated:
      (1) whether apolipoprotein E deficiency and older age promoted AAA formation, and
      (2) whether the local application of calcium phosphate affected the size of
      distant aortic segments. METHODS: AAA was induced by application of calcium
      phosphate to the infra-renal aortas of 3 and 7 month old male mice. AAA induction
      was assessed by calculating expansion of the infra-renal aortic diameter over 1-4
      weeks. Aortic samples were assessed to quantify calcification, macrophages
      infiltration, elastic lamellar degradation and apoptosis. Blood pressure was
      measured by the tail cuff method, and plasma concentrations of total cholesterol,
      low density lipoprotein and very low density lipoprotein cholesterol, and pro
      inflammatory cytokines were measured using commercially available kits. The
      maximum diameters of the aortic arch, thoracic and supra-renal aorta at sacrifice
      were measured by morphometry and the mean maximal diameter of these three aortic
      segments was calculated. RESULTS: The median expansion of the infra-renal aorta 2
      weeks after AAA induction was significantly greater in apolipoprotein E deficient
      (ApoE(-/-)) mice than in age- and gender-matched wild type controls [275.8% (IQR
      193.8%-348.5%) versus 94.7% (IQR 47.8%-163.4%), P = 0.02]. The greater aortic
      expansion in ApoE(-/-) mice was associated with aortic calcification, macrophage
      infiltration, elastic lamellar degradation and apoptosis of cells in the media
      and adventitia. The plasma low density lipoprotein/very low density lipoprotein
      cholesterol concentrations 2 weeks after AAA induction were positively correlated
      with the expansion of the infra-renal aorta induced by calcium phosphate. The
      median expansion of the infra-renal aorta 2 weeks after AAA induction was similar
      in 3 and 7 month old wild type mice. The local administration of calcium
      phosphate was associated with an increase in the mean maximal diameter of distant
      aortic segments, but not associated with changes in the concentrations of pro
      inflammatory markers in either the plasma or the spleen. CONCLUSION: This study
      suggests that apolipoprotein E deficiency, but not age, predisposes to AAA
      induced within the calcium phosphate model. Increased AAA expansion in ApoE(-/-)
      mice was associated with calcification, macrophage infiltration, elastic lamellar
      degradation, and cell apoptosis. Local application of calcium phosphate also
      promoted dilation of distant aortic segments.

PMID- 24858340
TI  - Induction of inducible nitric oxide synthase (iNOS) expression by oxLDL inhibits
      macrophage derived foam cell migration.
AB  - OBJECTIVE: Deletion of inducible nitric oxide synthase (iNOS) in apolipoprotein E
      knockout mice was shown to mitigate the extent of arteriosclerosis. Oxidized low
      density lipoprotein (oxLDL) inhibits macrophage migration and traps foam cells,
      possibly through a mechanism involving oxidative stress. Here, we addressed
      whether a reduction of iNOS-mediated oxidative stress remobilizes macrophage
      derived foam cells and may reverse plaque formation. METHODS: Migration of
      RAW264.7 cells and bone marrow cells was quantified using a modified Boyden
      chamber. iNOS expression, phalloidin staining, focal adhesion kinase
      phosphorylation, lipid peroxides, nitric oxide (NO) and reactive oxygen species
      (ROS) production were assessed. RESULTS: oxLDL treatment significantly reduced
      cell migration compared to unstimulated cells (p < 0.05). This migratory arrest
      was reversed by co-incubation with a pharmacologic iNOS inhibitor 1400 W (p <
      0.05) and iNOS-siRNA (p > 0.05). Furthermore, apoE/iNOS double knockout
      macrophages do not show migratory arrest in response to oxLDL uptake, compared to
      apoE knockout controls (p > 0.05). We documented significantly increased iNOS
      expression following oxLDL treatment and downregulation using 1400 W and small
      inhibitory RNA (siRNA). iNOS inhibition was associated with a reduction in NO and
      peroxynitrite (ONOO-)- and increased superoxide generation. Trolox treatment of
      RAW264.7 cells restored migration indicating that peroxynitrite mediated lipid
      peroxide formation is involved in the signaling pathway mediating cell arrest..
      CONCLUSIONS: Here, we provide pharmacologic and genetic evidence that oxLDL
      induced iNOS expression inhibits macrophage-derived foam cell migration.
      Therefore, reduction of peroxynitrite and possibly lipid hydroperoxide levels in
      plaques represents a valuable therapeutic approach to reverse migratory arrest of
      macrophage-derived foam cells and to impair plaque formation.

PMID- 24858341
TI  - Extracellular vesicles: specialized bone messengers.
AB  - Mammalian cells actively secrete factors that contribute to shape their
      microenvironment. These factors either travel freely or they are enclosed within
      the lipid bilayer of extracellular vesicles (EVs), and regulate the function of
      neighboring and distant cells. EVs are secreted by a wide spectrum of cell types
      and are found in various biological fluids. They convey their message by
      mediating the horizontal transfer of bioactive molecules, such as proteins, mRNAs
      and miRNAs, between cells. Recent studies showed the vital roles of EVs in a wide
      range of physiological and pathophysiological processes. In this review, we
      highlight the recent developments in the newly emerging EV field, including their
      biogenesis, molecular content and function. Moreover, we discuss the role of EVs
      in bone biology and their promising applications in diagnosis, drug development
      and regenerative therapy. 

PMID- 24858342
TI  - Transient suppression of AHR activity in early red seabream embryos does not
      prevent the disruption of peripheral nerve projection by 2,3,7,8
      tetrachlorodibenzo-p-dioxin.
AB  - The toxicity of dioxins such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is
      mainly mediated by an aryl hydrocarbon receptor (AHR), which regulates the
      transcription of multiple target genes including cytochrome P450 1A (CYP1A). Our
      pervious study identified the presence of TCDD-induced defects of peripheral
      nerve projection in red seabream (Pagrus major) embryos. However, it remains
      unclear whether the TCDD-induced peripheral neurotoxicity is mediated by the AHR.
      To assess the contribution of the red seabream AHR (rsAHR) signaling pathway to
      the neuronal toxicity, red seabream embryos at 10h post-fertilization (hpf) were
      treated for 80 min with TCDD (0, 0.3, 5.3, and 37 nM in seawater) alone or in
      combination with CH223191 (500 nM in seawater), which is an AHR antagonist. A
      preliminary in vitro reporter gene assay confirmed that TCDD-induced
      transcriptional activity via rsAHR1 and rsAHR2 was suppressed by CH223191
      treatment in a dose-dependent manner. CYP1A mRNA expression in embryos was
      determined by 2-step real time quantitative-polymerase chain reaction at 24 and
      120 hpf and in situ hybridization at 48, 72, 96 and 120 hpf. The morphology of
      the peripheral nerve system (PNS) was also microscopically observed by
      fluorescent staining using an anti-acetylated tubulin antibody at 120 hpf. CYP1A
      mRNA expression was dose-dependently induced by TCDD at all of the examined
      developing stages. The suppression of TCDD-induced CYP1A expression by CH223191
      treatment was observed in embryos at 24 and 48 hpf, while the effect of the rsAHR
      antagonist disappeared at 96 and 120 hpf. This phenomenon indicated the transient
      suppression of TCDD-induced rsAHR activation by CH223191 treatment. The
      immunostaining of peripheral nerves at 120 hpf demonstrated that the projections
      of the craniofacial nerve were altered in TCDD-treated embryos, and the frequency
      of TCDD-induced abnormal projections was not prevented by co-treatment with
      CH223191. These results indicate that the transient suppression of TCDD-induced
      rsAHR activation during the early developing stages of the red seabream does not
      influence the abnormal projection of peripheral nerves. In conclusion, transient
      rsAHR activation in the early stages of development is not involved in the
      neurotoxicity.

PMID- 24858343
TI  - The protein phosphatase 2A regulatory subunit B55alpha is a modulator of
      signaling and microRNA expression in acute myeloid leukemia cells.
AB  - We recently discovered that the protein phosphatase 2A (PP2A) B55alpha subunit
      (PPP2R2A) is under-expressed in primary blast cells and is unfavorable for
      remission duration in AML patients. In this study, reverse phase protein analysis
      (RPPA) of 230 proteins in 511 AML patient samples revealed a strong correlation
      of B55alpha with a number of proteins including MYC, PKC alpha, and SRC. B55alpha
      suppression in OCI-AML3 cells by shRNA demonstrated that the B subunit is a
      PKCalpha phosphatase. B55alpha does not target SRC, but rather the kinase
      suppresses protein expression of the B subunit. Finally, the correlation between
      B55alpha and MYC levels reflected a complex stoichiometric competition between B
      subunits. Loss of B55alpha in OCI-AML3 cells did not change global PP2A activity
      and the only isoform that is induced is the one containing B56alpha. In cells
      containing B55alpha shRNA, MYC was suppressed with concomitant induction of the
      competing B subunit B56alpha (PPP2R5A). A recent study determined that FTY-720, a
      drug whose action involves the activation of PP2A, resulted in the induction of
      B55alpha In AML cells, and a reduction of the B subunit rendered these cells
      resistant to FTY-720. Finally, reduction of the B subunit resulted in an increase
      in the expression of miR-191-5p and a suppression of miR-142-3p. B55alpha
      regulation of these miRs was intriguing as high levels of miR-191 portend poor
      survival in AML, and miR-142-3p is mutated in 2% of AML patient samples. In
      summary, the suppression of B55alpha activates signaling pathways that could
      support leukemia cell survival. 

PMID- 24858345
TI  - Investigation on the inclusion interaction of 4-sulfonatocalix[n]arenes with 1-(4
      nitrophenyl)piperazine.
AB  - The inclusion behaviors of 4-Sulfonatocalix[n]arenes (SCXn) (n=4, 6, 8) with 1-(4
      nitrophenyl)piperazine (NPP) were investigated by UV spectroscopy and
      fluorescence spectroscopy at different pH values (pH=3.05, 6.50, 8.40). The UV
      absorption and fluorescence intensity of NPP remarkably increased in presence of
      SCXn revealing formation of the inclusion complexes between NPP and SCXn.
      Moreover, the formation constants (K) of inclusion complexes were also determined
      by the non-linear fitting method, and the obtained data showed that the formation
      constants decreasedgradually with the increasing of the pH value. When the pH
      value was 3.05, the formation constant of NPP with SCX8 reached a maximum of
      1.7*10(7) L mol(-1). The stoichiometric ratio was verified to be 1:1 by the
      continuous variation method. Meanwhile FT-IR and DSC analysis also indicated that
      NPP could form the inclusion complex with SCXn. In order to explore the inclusion
      mechanism of NPP with SCXn, 1H NMR and molecular modeling studies were carried
      out and experimental results showed that the part of benzene ring of NPP
      penetrated into the hydrophobic cavity of SCXn.

PMID- 24858344
TI  - Bioenergetic analysis of ovarian cancer cell lines: profiling of histological
      subtypes and identification of a mitochondria-defective cell line.
AB  - Epithelial ovarian cancer (EOC) is the most lethal of all gynecological cancers,
      and encompasses distinct histological subtypes that have specific genetic and
      tissues-of-origin differences. Ovarian clear cell carcinoma (OCCC) represents
      approximately 10% of cases and has been termed a stress responsive cancer. OCCC
      is characterized by increased expression of oxidative stress and glycolysis
      related genes. In the present study, we hypothesized that bioenergetic profiling
      might uniquely distinguish OCCC from other EOC histological subtypes. Using an
      extracellular flux analyzer, OCCC lines (ES-2, TOV-21-G) were shown to be highly
      metabolically active, with high oxygen consumption rate (OCR) and high
      extracellular acidification rate (ECAR), indicative of enhanced mitochondrial
      oxidative phosphorylation and glycolytic rate, respectively. A high bioenergetics
      profile was associated with the cell lines' ability to form anchorage independent
      spheroids. Given their high glycolytic and mitochondrial activity, OCCC cells
      displayed strong sensitivity to 2-deoxy-D-glucose and Rotenone growth inhibition,
      although this chemosensitivity profile was not specific to only OCCC cells.
      Bioenergetic profiling also identified a non-OCCC cell line, OVCA420, to have
      severely compromised mitochondrial function, based on low OCR and a lack of
      stimulation of maximal respiration following application of the uncoupler FCCP.
      This was accompanied by mitochondrial morphology changes indicative of enhanced
      fission, increased expression of the mitochondrial fission protein Drp1, a loss
      of mitochondrial membrane potential and dependence on glycolysis. Importantly,
      this loss of mitochondrial function was accompanied by the inability of OVCA420
      cells to cope with hypoxic stress, and a compromised ability to stabilize HIF
      1alpha in response to 1% O2 hypoxia. This knowledge may be imperative for
      researchers planning to utilize this cell line for further studies of metabolism
      and hypoxia, and suggests that altered mitochondrial fission dynamics represents
      a phenotype of a subpopulation of EOCs. 

PMID- 24858346
TI  - Palladium(II) and zinc(II) complexes of neutral [N2O2] donor Schiff bases derived
      from furfuraldehyde: synthesis, characterization, fluorescence and corrosion
      inhibitors of ligands.
AB  - Metal complexes of Schiff bases derived from furfuraldehyde and 4,5-dimethyl-1,2
      phenylendiamine (L1) or 4,5-dichloro-1,2-phenylendiamine (L2) have been reported
      and characterized based on elemental analyses, IR, 1H NMR, UV-Vis, magnetic
      moment, molar conductance and thermal analysis. The complexes are found to have
      the formulae [PdL1-2]Cl2 and [ZnL1-2](AcO)2.H2O. The molar conductance data
      reveal that Pd(II) and Zn(II) chelates are ionic in nature and are of the type
      2:1 electrolytes. The spectral data are consistent with a square planar and
      tetrahedral geometry around Pd(II) and Zn(II), respectively, in which the ligands
      act as tetradentate ligands. The thermal behavior of some chelates is studied and
      the activation thermodynamic parameters are calculated using Coats-Redfern
      method. The corrosion inhibition of stainless steel types 410 and 304 in 1 M HCl
      using the synthesized Schiff bases as inhibitors have been studied by weight loss
      method. The obtained data considered these ligands as efficient corrosion
      inhibitors. The ligands and their metal complexes exhibited considerable
      antibacterial activity against Staphylococcusaureus, and Escherichiacoli and
      antifungal activity against Candida albicans.

PMID- 24858347
TI  - Photophysical insights on effect of gold nanoparticles over fullerene-porphyrin
      interaction in solution.
AB  - The present article reports the role of gold nanoparticles, i.e., AuNp (having
      diameter ~2-4nm), in non-covalent interaction between fullerenes (C60 and C70)
      and a monoporphyrin (1) in toluene. Both UV-vis and fluorescence measurements
      reveal considerable reduction in the average value of binding constant (Kav) for
      the C70-1 system (KC70-1(av)=19,300 dm3 mol(-1)) in presence of AuNp, i.e., KC70
      1-AuNp(av)=13,515 dm3 mol(-1) although no such phenomenon is observed in case of
      C60-1 system, viz., KC60-1(av)=1445 dm3 mol(-1) and KC60-1-AuNp(av)=1210 dm3 mol(
      1). DLS study reveals sizeable amount of increase in the particle size of C70-1
      AuNp nanocomposite, i.e., ~105 nm, compared to C60-1-AgNp system, e.g., ~5.5 nm
      which gives very good support in favor of decrease in the value of Kav for the
      former system. SEM study reveals that nanoparticles are dispersed in larger
      extent in case of C70-1-AuNp system. Time-resolved fluorescence study envisages
      that deactivation of the excited singlet state of 1 by C70 takes place at a
      faster rate in comparison to C60 in presence of gold nanoparticles.

PMID- 24858348
TI  - Conformational and vibrational analysis of 18-crown-6-alkali metal cation
      complexes.
AB  - Conformational analysis was performed for the 18-crown-6-alkali metal cation
      complexes, 18c6-AMCCs, using the CONFLEX method. The number of predicted
      conformations of the 18c6-Li+, Na+, K+, Rb+ and Cs+ complexes was 10, 24, 15, 9
      and 4 conformations, respectively. Electronic and geometrical structures were
      calculated for the predicted conformations at the HF, B3LYP, CAM-B3LYP, M06 and
      MP2 levels. Binding energies and enthalpies of the ground state conformations
      were also calculated. Vibrational, IR and Raman, spectra of free 18c6 and 18c6
      AMCCs were measured. Comparison between the calculated vibrational frequencies
      using multi-scale-factor scaling of the B3LYP force field and the experimental
      vibrational frequencies predicted that the 18c6-K+, Rb+ and Cs+ complexes exist
      in the D3d, C3v and C3v conformations, respectively. It was also predicted that
      the 18c6-Na+ complex exists in a D3d-like conformation. It was not possible to
      identify in what conformation the 18c6-Li+ complex exists.

PMID- 24858349
TI  - Ru-indoloquinoline complex as a selective and effective human telomeric G
      quadruplex binder.
AB  - Indoloquinoline and its derivatives have been reported to be a kind of efficient
      G-quadruplex binder and have been found to interact preferentially to
      intramolecular G-quadruplex and inhibit telomerase activity in human K562 cells
      and SW620 cells. In contrast to indoloquinoline derivatives, much less is known
      about the metal complex based on indoloquinoline or its derivative. In this
      report, we studied the interaction of ruthenium complex [Ru(bpy)2(itatp)]2+
      containing indoloquinoline moiety with human telomeric G-quadruplex DNA (Telo22)
      and c-myc G-quadruplex DNA (Pu27) by UV-visible (UV-Vis), fluorescence
      spectroscopy, fluorescent intercalator displacement (FID), thermal denaturation
      studies and CD spectroscopy. The results suggest that [Ru(bpy)2(itatp)]2+
      displays a strong pi-pi stacking interaction with human telomeric G-quadruplex
      with a high binding constant (~10(7) M(-1)), but just exhibits moderate binding
      affinity to c-myc G-quadruplex, thus showing significant selectivity to human
      telomeric G-quadruplex. The CD titration results indicate that
      [Ru(bpy)2(itatp)]2+ could effectively convert Telo22 into antiparallel G
      quadruplex conformation, while in the c-myc G-quadruplex case, instead of
      promoting Pu27 to fold into G-quadruplex, [Ru(bpy)2(itatp)]2+ destroys the
      parallel G-quadruplex structure of Pu27.

PMID- 24858350
TI  - Spectroscopic and biological studies of new binuclear metal complexes of a
      tridentate ONS hydrazone ligand derived from 4-amino-6-methyl-3-thioxo-3,4
      dihydro-1,2,4-triazin-5(2H)-one and 4,6-diacetylresorcinol.
AB  - The binuclear hydrazone, H2L, ligand derived from 4-amino-6-methyl-3-thioxo-3,4
      dihydro-1,2,4-triazin-5(2H)-one and 4,6-diacetylresorcinol, in the molar ratio
      2:1, and its copper(II), nickel(II), cobalt(II), zinc(II), cadmium(II),
      cerium(III), iron(III), oxovanadium(IV) and dioxouranium(VI) complexes have been
      synthesized. Structures of the ligand and its metal complexes were characterized
      by elemental analyses, spectral (infrared, electronic, mass, 1H NMR and ESR)
      data, magnetic susceptibility, molar conductivity measurements and thermal
      gravimetric analysis (TGA). The ligand acts as dibasic with two ONS tridentate
      sites. The bonding sites are the azomethine nitrogen, phenolate oxygen and sulfur
      atoms. The metal complexes exhibit different geometrical arrangements such as
      square planer, tetrahedral and octahedral. The Coats-Redfern equation was used to
      calculate the kinetic and thermodynamic parameters for the different thermal
      decomposition steps of some complexes. The ligand and its metal complexes showed
      antimicrobial activity towards Gram-positive bacteria (Staphylococcus aureus and
      Bacillus subtilis), Gram-negative bacteria (Salmonella typhimurium and
      Escherichia coli), yeast (Candida albicans) and fungus (Aspergillus fumigatus).
      Structural parameters of the ligand and its metal complexes were theoretically
      computed on the basis of semiempirical PM3 level, and the results were correlated
      with their experimental data.

PMID- 24858351
TI  - Molecular modeling, spectroscopic signature and NBO analysis of some building
      blocks of organic conductors.
AB  - Vibrational spectra with IR and Raman intensities in optimum state have been
      calculated for 2,2'-Bi-1,3-diselenole (commonly known as tetraselenafulvalene)
      and its halogen derivatives. All these calculations have been done by employing
      density functional theory (DFT) and second order Moller-Plesset perturbation
      theory (MP2) methods incorporated with suitable functionals and basis sets.
      Normal coordinate analysis has also been performed to calculate potential energy
      distributions (PEDs) to make a conspicuous assignment. The vibrational
      frequencies of all the four molecules have been assigned using PEDs and the
      results are compared with available values for the most similar molecules like
      tetrathiafulvalene. The molecular stability and bond strength have investigated
      by applying the Natural Bond Orbital (NBO) analysis. The energy gap between HOMO
      and LUMO is 2.041 eV for tetraselenafulvalene and it is slightly less than 2eV
      for halogen derivatives which implies that these molecules fall in the wide band
      gap semiconductor groups.

PMID- 24858352
TI  - Comparative thermodynamic properties, vibrational spectral studies, NBO and HOMO
      LUMO analyses of 3-chloro-2,4,5,6-tetrafluoropyridine and 4-bromo-2,3,5,6
      tetrafluoropyridine based on density functional theory.
AB  - Quantum mechanical calculations of energies, geometries and vibrational wave
      numbers of 3-chloro-2,4,5,6-tetrafluoropyridine and 4-bromo-2,3,5,6
      tetrafluoropyridine have been performed by DFT level of theory using B3LYP/6
      31+G(d) and B3LYP/6-311++G(d,p) as basis sets. The optimized geometrical
      parameters obtained by B3LYP method show good agreement with experimental data.
      The difference between the observed and scaled wave number values of most of the
      fundamentals is very small. A detailed interpretation of the FT-IR and FT-Raman
      spectra of 3-chloro-2,4,5,6-tetrafluoropyridine and 4-bromo-2,3,5,6
      tetrafluoropyridine were also reported. Molecular stability and bond strength
      were investigated by applying the natural bond orbital analysis (NBO). The
      calculated HOMO and LUMO energies show that charge transfer occurs in the
      molecules. Information about the size, shape, charge density distribution, and
      site of chemical reactivity of the molecules has been obtained by mapping
      electron density isosurface with electrostatic potential (ESP). Thermodynamic
      properties (heat capacity, entropy and enthalpy and Gibb's free energy) of the
      title compounds at different temperatures were calculated. 

PMID- 24858353
TI  - Synthesis, spectral characterization and DNA binding of Schiff-base metal
      complexes derived from 2-amino-3-hydroxyprobanoic acid and acetylacetone.
AB  - Four new metal complexes derived from the reaction of Cu(II), Co(II), Ni(II) and
      Zn(II) acetates with the Schiff-base ligand (H3L) resulted from the condensation
      of the amino acid 2-amino-3-hydroxyprobanoic acid (serine) and acetylacetone have
      been synthesized and characterized by, elemental analyses, ES-MS, IR, UV-Vis., 1H
      NMR, 13C NMR, ESR, thermal analyses (TGA and DTG) and magnetic measurements. The
      results showed that the Schiff-base ligand acts as bi-negative tridentate through
      the azomethine nitrogen, the deprotonated carboxylate oxygen and the enolic
      carbonyl oxygen. The optical band gaps measurements indicated the semi-conducting
      nature of these complexes. Molecular docking was used to predict the binding
      between the Schiff base ligand with the receptor of prostate cancer mutant H874Y.
      The interactions between the Cu(II) complex and calf thymus DNA (CT-DNA) have
      been studied by UV spectra. The results confirm that the Cu(II) complex binds to
      CT-DNA in an intercalative mode.

PMID- 24858354
TI  - Spectroscopic (FT-IR, FT-Raman, NMR and UV-Visible) and quantum chemical studies
      of molecular geometry, Frontier molecular orbital, NLO, NBO and thermodynamic
      properties of salicylic acid.
AB  - The solid phase FT-IR and FT-Raman spectra of 2-hydroxybenzoic acid (salicylic
      acid) have been recorded in the region 4000-400 and 4000-100 cm(-1) respectively.
      The optimized molecular geometry and fundamental vibrational frequencies are
      interpreted with the aid of structure optimizations and normal coordinate force
      field calculations based on density functional theory (DFT) method and a
      comparative study between Hartree Fork (HF) method at 6-311++G(d,p) level basis
      set. The calculated harmonic vibrational frequencies are scaled and they are
      compared with experimentally obtained FT-IR and FT-Raman spectra. A detailed
      interpretation of the vibrational spectra of this compound has been made on the
      basis of the calculated potential energy distribution (PED). The time dependent
      DFT method is employed to predict its absorption energy and oscillator strength.
      The linear polarizability (alpha) and the first order hyper polarizability (beta)
      values of the investigated molecule have been computed. The electronic
      properties, such as HOMO and LUMO energies, molecular electrostatic potential
      (MEP) are also performed. Stability of the molecule arising from hyper
      conjugative interaction, charge delocalization has been analyzed using natural
      bond orbital (NBO) analysis.

PMID- 24858355
TI  - Normal coordinate analysis and vibrational spectroscopy (FT-IR and FT-Raman)
      studies of 5-methyl-N-[4-(trifluoromethyl) phenyl]-isoxazole-4-carboxamide using
      density functional method.
AB  - Vibrational spectral analysis of 5-methyl-N-[4-(trifluoromethyl) phenyl]
      isoxazole-4-carboxamide is (5MN4TPI4C) molecule was carried out using FT-IR and
      FT-Raman spectroscopic techniques. The equilibrium geometry, harmonic vibrational
      wavenumbers, various bonding features have been computed using density functional
      B3LYP method with 6-311G(d,p) as basis set. The assignments of the vibrational
      spectra have been carried out with the aid of normal coordinate analysis (NCA)
      following the scaled quantum mechanical force field methodology (SQMFFM).
      Stability of the molecule arising from hyper conjugative interactions, charge
      delocalization has been analyzed using natural bond orbital (NBO) analysis. The
      non-linear optical (NLO) behavior of 5MN4TPI4C has been studied by determination
      of the electric dipole moment (MU) and hyperpolarizability (beta) by using
      B3LYP/6-311G(d,p) method. The molecular orbital compositions and their
      contributions to the chemical bonding are studied by Total density of energy
      states (TDOS), sum of alpha and beta electron (alphabetaDOS) density of states.
      Thermodynamic properties (heat capacity, entropy and enthalpy) of the title
      compound at different temperatures are calculated. 

PMID- 24858356
TI  - Survey on the complexation character of p-sulfonatocalix[n]arenes and Caffeic
      acid.
AB  - In this work the inclusion complex formation of Caffeic acid (CA) with p
      sulfonatocalix[n]arenes (SCXn, n=4, 6, 8) is reported aiming to improve the
      antioxidant activity, thermal stability and photostability properties of CA.
      Evidence for the formation was obtained using fluorescence spectroscopy, nuclear
      magnetic resonance spectroscopy (NMR), pulsed field gradient NMR (PFG-NMR),
      Fourier transform infrared spectroscopy (FT-IR), differential scanning
      calorimetry (DSC) and scanning electron microphotographs (SEM). Experimental
      conditions including concentrations of SCXn and pH were investigated for the
      inclusion formation in detail. The results showed that CA was able to form
      inclusion complexes with SCXn in a molar ratio of 1:1, and the formation
      constants were varied with the pH conditions. NMR spectroscopy indicated that
      both the aromatic ring and the vinyl group of CA were partially covered by SCXn. 

PMID- 24858357
TI  - Comparison effects and electron spin resonance studies of alpha-Fe2O4 spinel type
      ferrite nanoparticles.
AB  - alpha-Fe2O4 spinel type ferrite nanoparticles have been synthesized by
      cetyltrimethylammonium bromide (CTAB) and ethylenediaminetetraacetic acid (EDTA)
      assisted hydrothermal route by using NaOH solution. Electron spin resonance
      (ESR/EPR) measurements of alpha-Fe2O4 nanoparticles have been performed by a
      conventional x-band spectrometer at room temperature. The comparison effect of
      nanoparticles prepared by using CTAB and EDTA in different alpha-doping on the
      structural and morphological properties have been investigated in detail. The
      effect of EDTA-assisted synthesis for alpha-Fe2O4 nanoparticles are refined, and
      thus the spectroscopic g-factor are detected by using ESR signals. These samples
      can be considered as great benefits for magnetic recording media, electromagnetic
      and drug delivery applications. 

PMID- 24858358
TI  - Spectroscopic, analytical and DFT calculation studies of two novel Al3+ complexes
      derived from 2,4,6-tri-(2-pyridyl)-1,3,5-triazine (TPTZ).
AB  - In this study TPTZ is used exclusively as an analytical reagent for the
      determination of micro amounts of Al3+ ions with high accuracy and lower
      detection limit, which reach 2.7 ppm. The developed blue color of Al3+-TPTZ
      complex was used selectivity to determine the concentration and the geometry of
      the Al3+ complex using continuous variation and molar ratio methods. Also, the
      novel Al3+ complexes derived from the reaction of TPTZ were synthesized. The
      solid complexes were characterized by elemental analyses, spectral (IR, UV-vis.,
      1H NMR, mass) and magnetic measurements. The isolated complexes have the general
      formulae, [Al(TPTZ)Cl3].H2O.11/2EtOH (1:1; M:L) and [Al2(TPTZ)Cl6(EtOH)2] (2:1;
      M:L). IR spectra indicate that TPTZ behaves in a bidentate manner in case of 1:1
      and 2:1 (M:L). Elemental analyses and mass spectra of the complexes suggest the
      existence of an octahedral structure around the Al3+ ions. DFT calculations were
      used to determine the geometry of complexes.

PMID- 24858360
TI  - Introductory paragraph - Volume 28, Issue 6.

PMID- 24858359
TI  - Synthesis, molecular structure, FT-IR, Raman, XRD and theoretical investigations
      of (2E)-1-(5-chlorothiophen-2-yl)-3-(naphthalen-2-yl)prop-2-en-1-one.
AB  - A novel (2E)-1-(5-chlorothiophen-2-yl)-3-(naphthalen-2-yl)prop-2-en-1-one
      [C17H11ClOS] compound has been synthesized and its structure has been
      characterized by FT-IR, Raman and single-crystal X-ray diffraction techniques.
      The isomers, optimized geometrical parameters, normal mode frequencies and
      corresponding vibrational assignments of the compound have been examined by means
      of the density functional theory method, employing, the Becke-3-Lee-Yang-Parr
      functional and the 6-311+G(3df,p) basis set. Reliable vibrational assignments and
      molecular orbitals have been investigated by the potential energy distribution
      and natural bonding orbital analyses, respectively. The compound crystallizes in
      the monoclinic space group P21/c with the unit cell parameters a=5.7827(8)A,
      b=14.590(2)A, c=16.138(2)A and beta=89.987 ( degrees ). The CC bond of the
      central enone group adopts an E configuration. There is a good agreement between
      the theoretically predicted structural parameters and vibrational frequencies and
      those obtained experimentally.

PMID- 24858361
TI  - National Institute for Health and Care Excellence stroke rehabilitation guidance 
      is it useful, usable, and based on best evidence?
AB  - In the UK, the National Institute for Health and Care Excellence (NICE) is
      responsible for producing clinical guidance based on sound evidence. In 2013 they
      produced guidance on Stroke Rehabilitation and this editorial outlines why this
      is not a useful guide for clinicians or commissioners. Primarily this is because
      NICE used inappropriate methods; the methods used are appropriate for evaluating
      drugs, but are inappropriate when applied to any complex intervention. Moreover,
      the actual recommendations are written in clinically unhelpful language. Future
      rehabilitation guidance should include ensuring that the team responsible for the
      guidance are all familiar with and understand the biospsychosocial model of
      illness and the nature of the rehabilitation process (which is not synonymous
      with therapy), setting a relevant and appropriate scope for a guideline, agreeing
      to use all evidence relevant to a particular question, and using a more
      appropriate way to evaluate evidence while recognising that rehabilitation is a
      complex intervention. 

PMID- 24858362
TI  - Femoroacetabular impingement: prevention or intervention? The sports physician's
      quandary.

PMID- 24858364
TI  - Oral salmon calcitonin enhances insulin action and glucose metabolism in diet
      induced obese streptozotocin-diabetic rats.
AB  - We previously reported that oral delivery of salmon calcitonin (sCT) improved
      energy and glucose homeostasis and attenuated diabetic progression in animal
      models of diet-induced obesity (DIO) and type 2 diabetes, although the
      glucoregulatory mode of action was not fully elucidated. In the present study we
      hypothesized that oral sCT as pharmacological intervention 1) exerted anti
      hyperglycemic efficacy, and 2) enhanced insulin action in DIO-streptozotocin (DIO
      STZ) diabetic rats. Diabetic hyperglycemia was induced in male selectively bred
      DIO rats by a single low dose (30mg/kg) injection of STZ. Oral sCT by gavage was
      delivered as once-daily administration with lead-in (2mg/kg) and maintenance
      (0.5mg/kg) dose of oral sCT for a total of 21 days. Food intake, body weight,
      blood glucose, HbA1c, glucose and insulin tolerance test, and parameters of
      insulin sensitivity were investigated. Plasma glucoregulatory hormones and
      pancreatic insulin content were analyzed. Oral sCT treatment induced a pronounced
      anorectic action during the 7 days lead-in period and markedly reduced food
      intake and body weight in conjunction with improved glucose homeostasis. During
      the maintenance period, oral sCT normalized food intake and attenuated weight
      loss, albeit sustained glycemic control by reducing fasting blood glucose and
      HbA1c levels compared to those of vehicle-treated rats at the end of study.
      Notably, plasma levels of insulin, glucagon, leptin and adiponectin were
      unaltered, albeit insulin action was enhanced in conjunction with protection of
      pancreatic insulin content. The results of the present study indicate that oral
      sCT exerts a novel insulin-sensitizing effect to improve glucose metabolism in
      obesity and type 2 diabetes. 

PMID- 24858365
TI  - Antiproteinuric effect of pirfenidone in a rat model of anti-glomerular basement
      membrane glomerulonephritis.
AB  - While pirfenidone has been established as an effective anti-fibrosis remedy,
      whether or not its antifibrotic effect contributes to a reduction of proteinuria
      remains unclear. We investigated the renoprotective properties of pirfenidone in
      an anti-glomerular basement membrane (GBM) glomerulonephritis model both
      prophylactically and therapeutically to determine its profile against
      proteinuria. In the prophylactic regimen, pirfenidone was treated immediately
      after anti-serum injection. We observed a significant reduction in the
      progression of proteinuria (P<0.05) and decline in renal function (P<0.01) and
      also noted histological improvement in renal injury. These effects appeared to be
      due to the maintained expression of nephrin and podocin on podocytes as well as
      the reduced expression of profibrotic factors like transforming growth factor
      beta (TGF-beta). The expression of nephrin mRNA was strongly negatively
      correlated with the amount of urinary protein excretion (R=-0.84, P<0.001),
      implicating podocyte damage in the outcome of proteinuria (R(2)=0.70). These
      results suggest that preservation of podocytes with the pirfenidone treatment may
      have resulted in the decrease of proteinuria. In contrast, when the therapeutic
      regimen was initiated 2 weeks after nephritis induction, pirfenidone had little
      effect on the progression of proteinuria, although the decline of renal function
      and fibrosis were suppressed. Taken together, present findings suggested that
      pirfenidone prevented the progression of proteinuria only when administered
      prophylactically but was still able to ameliorate the decline of renal function
      independent of proteinuria. In conclusion, pirfenidone as a prophylactic regimen
      reduces proteinuria in anti-GBM nephritis via preservation of podocytes with
      markedly reduced efficacy when administered as a therapeutic regimen. 

PMID- 24858363
TI  - The influence of 5-HTTLPR genotype on the association between the plasma
      concentration and therapeutic effect of paroxetine in patients with major
      depressive disorder.
AB  - INTRODUCTION: The efficacy of treatment with selective serotonin reuptake
      inhibitors in patients with major depressive disorder (MDD) can differ depending
      on the patient's serotonin transporter-linked polymorphic region (5-HTTLPR)
      genotype, and the effects of varying plasma concentrations of drugs can also
      vary. We investigated the association between the paroxetine plasma concentration
      and clinical response in patients with different 5-HTTLPR genotypes. METHODS:
      Fifty-one patients were enrolled in this study. The Montgomery-Asberg Depression
      Rating Scale (MADRS) was used to evaluate patients at 0, 1, 2, 4, and 6 weeks.
      The patients' paroxetine plasma concentrations at week 6 were measured using high
      performance liquid chromatography. Additionally, their 5-HTTLPR polymorphisms
      (alleles S and L) were analyzed using a polymerase chain reaction with specific
      primers. We divided the participants into two groups based on their L haplotype:
      the SS group and the SL and LL group. We performed single and multiple regression
      analyses to investigate the associations between MADRS improvement and paroxetine
      plasma concentrations or other covariates for each group. RESULTS: There were no
      significant differences between the two groups with regard to demographic or
      clinical data. In the SS group, the paroxetine plasma concentration was
      significantly negatively correlated with improvement in MADRS at week 6. In the
      SL and LL group, the paroxetine plasma concentration was significantly positively
      correlated with improvement in MADRS at week 6 according to the results of the
      single regression analysis; however, it was not significantly correlated with
      improvement in MADRS at week 6 according to the results of the multiple
      regression analysis. CONCLUSION: Among patients with MDD who do not respond to
      paroxetine, a lower plasma concentration or a lower oral dose of paroxetine might
      be more effective in those with the SS genotype, and a higher plasma
      concentration might be more effective in those with the SL or LL genotype.

PMID- 24858367
TI  - The design of nitric oxide donor drugs: s-nitrosothiol tDodSNO is a superior
      photoactivated donor in comparison to GSNO and SNAP.
AB  - We have recently developed tert-dodecane S-nitrosothiol (tDodSNO) as a
      photoactivated nitric oxide (NO) donor. We here compare the potency of tDodSNO to
      S-nitrosoglutathione (GSNO) and S-nitroso-N-acetylpenicillamine (SNAP), drugs
      which are also based upon the S-nitrosothiol functionality and have been
      extensively used for NO release studies. Photoactivation in vitro, at a
      clinically relevant light fluence rate (200W/m(2)), demonstrated that tDodSNO
      released much higher levels of NO than either GSNO or SNAP. When evaluated in an
      ex vivo aortic ring vasorelaxation assay, tDodSNO was also the only drug to
      exhibit a photodynamic response, with an 8 fold decrease in EC50 (8.1-1.0uM) upon
      irradiation. While both GSNO and SNAP induced NO dependent vasorelaxation at
      lower concentrations than tDodSNO (EC50's of 158 and 38nM respectively), this
      activity was due to their rapid metabolic decomposition, and could not be
      modulated by photoactivation. Additionally, tDodSNO's photodynamic response
      allowed vascular tone to be directly regulated by light intensity. Molecular
      modeling of drug properties suggested that these differences in activity could be
      attributed to a combination of an increase in tDodSNO's hydrophobicity, and
      substantial steric shielding of molecule's S-nitrosothiol group from solvent
      interactions. In conclusion, our study demonstrates that tDodSNO is currently the
      most effective known s-nitrosothiol for phototherapeutic applications. 

PMID- 24858366
TI  - Endocannabinoid contribution to Delta9-tetrahydrocannabinol discrimination in
      rodents.
AB  - The mechanism through which marijuana produces its psychoactive effects is
      Delta(9)-tetrahydrocannabinol (THC)-induced activation of cannabinoid CB1
      receptors. These receptors are normally activated by endogenous lipids, including
      anandamide and 2-arachidonoyl glycerol (2-AG). A logical "first step" in
      determination of the role of these endocannabinoids in THC's psychoactive effects
      is to investigate the degree to which pharmacologically induced increases in
      anandamide and/or 2-AG concentrations through exogenous administration and/or
      systemic administration of inhibitors of their metabolism, fatty acid amide
      hydrolase (FAAH) or monoacylglycerol lipase (MAGL), respectively, share THC's
      discriminative stimulus effects. To this end, adult male mice and rats were
      trained to discriminate THC (5.6 and 3mg/kg, respectively). In Experiment 1,
      exogenous administration of anandamide or 2-AG did not substitute for THC in mice
      nor was substitution enhanced by co-administration of the FAAH or MAGL
      inhibitors, URB597 and N-arachidonyl maleimide (NAM), respectively. Significant
      decreases in responding may have prevented assessment of adequate endocannabinoid
      doses. In mice trained at higher baseline response rates (Experiment 2), the FAAH
      inhibitor PF3845 (10mg/kg) enhanced anandamide substitution for THC without
      producing effects of its own. The MAGL inhibitor JZL184 increased brain levels of
      2-AG in vitro and in vivo, increased THC-like responding without co
      administration of 2-AG. In rats, neither URB597 nor JZL184 engendered significant
      THC-appropriate responding, but co-administration of these two enzyme inhibitors
      approached full substitution. The present results highlight the complex interplay
      between anandamide and 2-AG and suggest that endogenous increases of both
      endocannabinoids are most effective in elicitation of THC-like discriminative
      stimulus effects. 

PMID- 24858368
TI  - Cardioprotection against doxorubicin by metallothionein Is associated with
      preservation of mitochondrial biogenesis involving PGC-1alpha pathway.
AB  - Metallothionein (MT) has been shown to inhibit cardiac oxidative stress and
      protect against the cardiotoxicity induced by doxorubicin (DOX), a potent and
      widely used chemotherapeutic agent. However, the mechanism of MT's protective
      action against DOX still remains obscure. Mitochondrial biogenesis impairment has
      been implicated to play an important role in the etiology and progression of DOX
      induced cardiotoxicity. Increasing evidence indicates an intimate link between MT
      mediated cardioprotection and mitochondrial biogenesis. This study was aimed to
      explore the possible contribution of mitochondrial biogenesis in MT's
      cardioprotective action against DOX. Adult male MT-I/II-null (MT(-/-)) and wild
      type (MT(+/+)) mice were given a single dose of DOX intraperitoneally. Our
      results revealed that MT deficiency significantly sensitized mice to DOX-induced
      cardiac dysfunction, ultrastructural alterations, and mortality. DOX disrupted
      cardiac mitochondrial biogenesis indicated by mitochondrial DNA copy number and
      decreased mitochondrial number, and these effects were greater in MT(-/-) mice.
      Basal MT effectively protected against DOX-induced inhibition on the peroxisome
      proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha), a key
      regulator of mitochondrial biogenesis, and its downstream factors including
      mitochondrial transcription factor A. Moreover, MT was found to preserve the
      protein expression of manganese superoxide dismutase, a transcriptional target of
      PGC-1alpha. in vitro study showed that MT absence augmented DOX-induced increase
      of mitochondrial superoxide production in primary cultured cardiomyocytes. These
      findings suggest that MT's cardioprotection against DOX is mediated, at least in
      part, by preservation of mitochondrial biogenesis involving PGC-1alpha pathway. 

PMID- 24858369
TI  - Wogonin inhibits LPS-induced tumor angiogenesis via suppressing PI3K/Akt/NF
      kappaB signaling.
AB  - Wogonin has been shown to have anti-angiogenesis and anti-tumor effects. However,
      whether wogonin inhibits LPS-induced tumor angiogenesis is not well known. In
      this study, we investigated the effect of wogonin on inhibiting LPS-induced tumor
      angiogenesis and further probed the underlying mechanisms. ELISA results revealed
      that wogonin could suppress LPS-induced VEGF secretion from tumor cells.
      Transwell assay, tube formation assay, rat aortic ring assay and CAM model were
      used to evaluate the effect of wogonin on angiogenesis induced by MCF-7 cell
      (treated with LPS) in vitro and in vivo. The inhibitory effect of wogonin on
      angiogenesis in LPS-treated MCF-7 cells was then confirmed by the above in vitro
      and in vivo assays. The study of the molecular mechanism showed that wogonin
      could suppress PI3K/Akt signaling activation. Moreover, wogonin inhibited nuclear
      translocation of NF-kappaB and its binding to DNA. The result of real-time PCR
      and luciferase reporter assay suggested that VEGF expression was down-regulated
      by wogonin primarily at the transcriptional level. IGF-1 and p65 expression
      plasmid were used to activate PI3K/Akt and NF-kappaB pathways, and to observe the
      effect of wogonin on the simualtion of PI3K/Akt/NF-kappaB signaling. Taken
      together, the result suggested that wogonin was a potent inhibitor of tumor
      angiogenesis and provided a new insight into the mechanisms of wogonin against
      cancer. 

PMID- 24858370
TI  - Cardioprotective efficacy against reperfusion injury of EMD-87580: Comparison to
      ischemic postconditioning.
AB  - Previous results show that prolonged treatment with EMD-87580 (EMD) NHE-1 blocker
      attenuates and reverses postinfarction remodelling. Our aim was to evaluate the
      effects of the treatment of EMD compared to ischemic postconditioning (IPO) in a
      model of regional ischemia. Isolated hearts were subjected to 40-min coronary
      occlusion followed by 60-min reperfusion (IC). Other hearts were treated with EMD
      5MUM during the first 10min of reperfusion or submitted to one cycle of 2min of
      reperfusion and 2min of ischemia as IPO protocol. Infarct sizes (IS),
      postischemic myocardial and vascular functions were assessed. The concentration
      of thiobarbituric reactive substances (TBARS), reduced glutathione (GSH) and
      expression of phosphorylated forms of ERK1/2, Akt, GSK-3beta, eNOS were analyzed.
      MnSOD cytosolic activity - as an index of mitochondrial permeability - was also
      measured. EMD treatment and IPO decreased IS~50% and significantly improved the
      postischemic recovery of contractility and coronary perfusion. TBARS decreased
      and GSH increased after interventions compared to the values observed in IC
      hearts. MnSOD cytosolic activity increased in IC group and was significantly
      attenuated by EMD and abolished in IPO hearts. The content of P-ERK1/2 increased
      whereas P-Akt, P-GSK-3beta and P-eNOS decreased in IC hearts. EMD treatment and
      IPO reversed these changes. The present data show that EMD treatment at the
      beginning of reperfusion-similarly to IPO- limited infarct size and attenuated
      the postischemic impairment of myocardial function through reactive oxygen
      species-mediated ERK1/2/Akt/GSK-3beta/eNOS pathways. 

PMID- 24858371
TI  - Potentiation of insulin secretion and improvement of glucose intolerance by
      combining a novel G protein-coupled receptor 40 agonist DS-1558 with glucagon
      like peptide-1 receptor agonists.
AB  - G protein-coupled receptor 40 (GPR40) is a Gq-coupled receptor for free fatty
      acids predominantly expressed in pancreatic beta-cells. In recent years, GPR40
      agonists have been investigated for use as novel therapeutic agents in the
      treatment of type 2 diabetes. We discovered a novel small molecule GPR40 agonist,
      (3S)-3-ethoxy-3-(4-{[(1R)-4-(trifluoromethyl)-2,3-dihydro-1H-inden-1
      yl]oxy}phenyl)propanoic acid (DS-1558). The GPR40-mediated effects of DS-1558 on
      glucose-stimulated insulin secretion were evaluated in isolated islets from GPR40
      knock-out and wild-type (littermate) mice. The GPR40-mediated effects on glucose
      tolerance and insulin secretion were also confirmed by an oral glucose tolerance
      test in these mice. Furthermore, oral administration of DS-1558 (0.03, 0.1 and
      0.3mg/kg) significantly and dose-dependently improved hyperglycemia and increased
      insulin secretion during the oral glucose tolerance test in Zucker fatty rats,
      the model of insulin resistance and glucose intolerance. Next, we examined the
      combination effects of DS-1558 with glucagon like peptide-1 (GLP-1). DS-1558 not
      only increased the glucose-stimulated insulin secretion by GLP-1 but also
      potentiated the maximum insulinogenic effects of GLP-1 after an intravenous
      glucose injection in normal Sprague Dawley rats. Furthermore, the glucose
      lowering effects of exendin-4, a GLP-1 receptor agonist, were markedly
      potentiated by the DS-1558 (3mg/kg) add-on in diabetic db/db mice during an
      intraperitoneal glucose tolerance test. In conclusion, our results indicate that
      add-on GPR40 agonists to GLP-1 related agents might be a potential treatment
      compared to single administration of these compounds. Therefore the combinations
      of these agents are a novel therapeutic option for type 2 diabetes. 

PMID- 24858372
TI  - Serum microRNA expression profiling predict response to R-CHOP treatment in
      diffuse large B cell lymphoma patients.
AB  - MicroRNAs (miRNAs) are stably expressed in serum, which could serve as great
      potential prognostic biomarkers in a variety of diseases, including various
      cancers. We analyzed the miRNA expression profiles to investigate the role of
      serum miRNA in predicting response to rituximab, cyclophosphamide, Adriamycin,
      vincristine, and prednisone (R-CHOP) treatment in diffuse large B cell lymphoma
      (DLBCL) patients. The present study proceeded through three phases. In the
      discovery phase, real-time polymerase chain reaction (PCR)-based miRNA profiling
      was used to test the difference in levels of serum miRNAs between 20 patients
      with complete remission after 6 cycles of R-CHOP treatment and 20 patients with
      primary refractory disease matched by age, sex, and stage. After the marker
      selection phase, the selected serum miRNAs were validated in 133 patients using
      the quantitative reverse transcriptase-PCR assays during the validation phases.
      Fifteen serum miRNAs were found to be altered more than 10-fold by real-time PCR
      based miRNA profiling between the complete remission and primary refractory
      groups. The levels of five miRNAs (miR-224, miR-455-3p, miR-1236, miR-33a, and
      miR-520d-3p) were significantly associated with response to R-CHOP treatment in
      DLBCL patients. The five-miRNA signature was also a significant predictor of
      response independent from the International Prognostic Index score. The
      expression levels of these five serum miRNAs may serve as novel prognostic
      biomarkers to predict the clinical outcome of DLBCL patients treated with R-CHOP
      regimen.

PMID- 24858373
TI  - How do we face patients' expectations in joint arthroplasty?
AB  - INTRODUCTION: Patients' expectations have become increasingly important over the
      last decade, as the fulfilment of preoperative expectations has been shown to be
      associated with postoperative satisfaction. Understanding the pattern of
      patients' expectations is necessary to provide a better basis for recommendations
      to patients opting for arthroplasty. The aim of this study was to show patients'
      expectations of joint replacement surgery in Germany and to elucidate factors,
      which might have an influence. MATERIALS AND METHODS: A retrospective analysis of
      anonymously collected data was performed on people participating in a patient
      information event for joint replacement surgery. They were asked to complete a
      survey, which consisted of five questions requesting demographic data and three
      questions regarding preoperative expectations. The latter were taken from the New
      Knee Society Score. An expectation score (0-12 points) was generated by adding
      the single point values of the three questions. RESULTS: 180 attendees were
      included in this study. The distribution of patients' expectations was remarkably
      skewed towards high expectations, the mean expectation score was 10.17. 87.2 % of
      participants had high and very high expectations and only 12.8 % had low and
      moderate expectations. Patients' expectations were independent of age and
      previous participation in a patient information event. Female gender and a
      history of arthroplasty led to a slightly higher expectation score. Patients with
      isolated knee pain had significantly lower expectations than patients suffering
      from isolated hip pain. CONCLUSIONS: This study shows that the majority of
      patients have high expectations regarding joint replacement surgery. To improve
      postoperative patients' satisfaction a straightforward physician-patient
      communication is necessary to prevent patients from potentially unrealistic
      expectations and therefore dissatisfaction with surgery.

PMID- 24858374
TI  - Avian blood induced intranuclear translocation of STAT3 via the chicken leptin
      receptor.
AB  - Leptin is a multi-functional adipokine in vertebrates. The leptin gene and
      protein are found in many vertebrates; however, the existence of leptin in birds
      remains controversial. Here we detected leptin-like activity in avian blood using
      chicken leptin receptor (chLEPR) and green fluorescent protein (GFP)-fused
      chicken signal transducer and activator of transcription (chSTAT3) co-expressed
      in CHO-K1 cells (CHO-chLEPR/STAT3). We validated that rat serum specifically
      induces intranuclear migration of GFP-fused chSTAT3 (GFP-chSTAT3) in CHO
      chLEPR/STAT3 cells, but not in CHO-K1 cells expressing GFP-STAT3 (CHO-chSTAT3)
      before testing the avian blood samples. Blood of chickens (Gallus gallus), wild
      jungle crows (Corvus macrorhynchos), and carrion crows (Corvus corone)
      accumulated the GFP signal into nuclei, and frequency varied in each blood
      sample. Western blotting showed that chicken and crow blood samples specifically
      phosphorylated GFP-chSTAT3 in the chLEPR-transfected cells. These results
      indicate that avian blood contains a leptin-like molecule that specifically binds
      to LEPR, suggesting that the leptin system is conserved across all vertebrate
      classes. 

PMID- 24858375
TI  - Wistar rats acquire and maintain self-administration of 20 % ethanol without
      water deprivation, saccharin/sucrose fading, or extended access training.
AB  - RATIONALE: Operant self-administration (SA) is an important model of motivation
      to consume ethanol (EtOH), but low rates of voluntary consumption in rats are
      thought to necessitate water deprivation and saccharin/sucrose fading for
      acquisition of responding. OBJECTIVES: Here, we sought to devise an effective
      model of SA that does not use water deprivation or saccharin/sucrose fading.
      METHODS: First, we tested if Wistar rats would acquire and maintain SA behavior
      of 20 % EtOH under two conditions, water deprivation (WD) and non-water
      deprivation (NWD). Second, we tested the efficacy of our SA procedure by
      confirming a prior study which found that the NK1 antagonist L822429 specifically
      blocked stress-induced reinstatement of EtOH seeking but not SA. Finally, we
      assessed the effect of naltrexone, an FDA-approved medication for alcohol
      dependence that has been shown to suppress EtOH SA in rodents. RESULTS: Lever
      presses (LPs) and rewards were consistent with previous reports that utilized WD
      and saccharin/sucrose fading. Similar to previous findings, we found that L822429
      blocked stress-induced reinstatement but not baseline SA of 20 % EtOH. Moreover,
      naltrexone dose-dependently decreased alcohol intake and motivation to consume
      alcohol for rats that are self-administering 20 % EtOH. CONCLUSIONS: Our findings
      provide a method for voluntary oral EtOH SA in rats that is convenient for
      experimenters and eliminates the potential confound of sweeteners in EtOH-operant
      SA studies. Unlike models that use intermittent access to 20 % EtOH, this method
      does not induce escalation, and based on pharmacological experiments, it appears
      to be driven by the positive reinforcing effects of EtOH.

PMID- 24858376
TI  - Effects of acute treatment with a tryptophan-rich protein hydrolysate on plasma
      amino acids, mood and emotional functioning in older women.
AB  - RATIONALE: Effective functioning of the neurotransmitter serotonin is important
      for optimal cognitive and emotional function. Dietary supplements able to
      increase availability to the brain of the precursor amino acid, tryptophan (TRP),
      and thereby enhance serotonin synthesis, can have measurable impact on these
      psychological processes. OBJECTIVES: This study involves a randomised controlled
      trial of a TRP-rich egg-white protein hydrolysate (DSM Nutritional Products Ltd.,
      Switzerland) on plasma amino acids, cognition, mood and emotional processing in
      older women. METHODS: Following a baseline test day without treatment, 60 healthy
      women aged 45-65 years received drinks containing either 2 or 4 g of TRP-rich
      protein hydrolysate product or 3.11 g casein hydrolysate as a control. One hour
      later, they undertook a 2-h battery of cognitive and emotional tests. RESULTS:
      The TRP-rich protein hydrolysate produced the expected dose-dependent increase in
      the ratio of plasma TRP to competing large neutral amino acids. TRP-rich protein
      hydrolysate (2 g only) prevented both the decline in wellbeing and increase in
      fatigue seen over the test session in the control group. This treatment dose
      resulted in a significant shift in emotional processing towards positive words
      and reduced negative bias in assessing negative facial expressions. Effects on
      cognition were small and not statistically reliable and are not reported here.
      However, there was no evidence for any adverse effects. CONCLUSIONS: Consumption
      of a low dose of TRP-rich protein hydrolysate may have beneficial effects on
      emotional function that could promote feelings of wellbeing, possibly conferring
      resistance to deterioration in mood in healthy subjects or depressive episodes.

PMID- 24858377
TI  - Acute effects of low and high dose alcohol on smoking lapse behavior in a
      laboratory analogue task.
AB  - RATIONALE: Smoking lapses (i.e., returns to smoking after quitting) often occur
      following alcohol consumption with observational data suggesting greater
      quantities of alcohol lead to greater risk. However, a causal dose-dependent
      effect of alcohol consumption on smoking lapse behavior has not been established,
      and the mechanisms that might account for such an effect have not been tested.
      OBJECTIVES: In a within-subjects design, we examined the effects of low- (0.4
      g/kg) and high-dose (0.8 g/kg) alcohol, relative to placebo, on smokers' ability
      to resist initiating smoking after acute smoking abstinence. METHODS:
      Participants were 100 heavy alcohol drinkers, smoking 10-30 cigarettes per day.
      Across three separate days, participants consumed placebo, low-dose, or high-dose
      alcohol following 3 h of smoking abstinence and, 35 min later, were offered the
      opportunity to smoke while resisting smoking was monetarily reinforced
      proportional to the amount of time delayed. RESULTS: Consistent with a dose
      response effect, participants smoked 3.35 min (95 % confidence intervals (CI) [
      7.09, 0.40], p = .08) earlier following low-dose alcohol and 6.36 min (95 % CI [
      9.99, -2.73], p = .0006) earlier following high-dose alcohol compared to drinking
      a placebo beverage. Effects of dose on smoking behavior were partially mediated
      by increases in urge to smoke. There was no evidence that alcohol's effects on
      urge to smoke or ability to resist smoking were mediated through its stimulating
      or sedating effects. CONCLUSIONS: Alcohol can reduce the ability to resist
      smoking in a dose-dependent fashion, in part, due to its effect on increasing the
      intensity of smoking urges.

PMID- 24858378
TI  - A human cancer xenograft model utilizing normal pancreatic duct epithelial cells
      conditionally transformed with defined oncogenes.
AB  - Pancreatic ductal adenocarcinomas (PDACs) are considered to arise through
      neoplastic transformation of human pancreatic duct epithelial cells (HPDECs). In
      order to evaluate the biological significance of genetic and epigenetic
      alterations in PDACs, we isolated primary HPDECs and established an in vitro
      carcinogenesis model. Firstly, lentivirus-mediated transduction of KRAS(G12V),
      MYC and human papillomavirus 16 (HPV16) E6/E7 under the control of a tetracyclin
      inducible promoter efficiently immortalized and transformed primary HPDECs, which
      gave rise to adenocarcinomas subcutaneously in an immune-deficient mouse
      xenograft model, depending on expression of the four genes. The tumors regressed
      promptly upon shutting-off the oncogenes, and the remaining tissues showed
      histological features corresponding to normal ductal structures with simple
      columnar epithelium. Reexpression of the oncogenes resulted in development of
      multiple PDACs through pancreatic intraepithelial neoplasia-like structures. We
      also succeeded in efficient immortalization of primary HPDECs with transduction
      of mutant CDK4, cyclin D1 and TERT. The cells maintained a normal diploid status
      and formed duct-like structures in a three-dimensional culture. In combination
      with p53 silencing, KRAS(G12V) alone was sufficient to fully transform the
      immortalized HPDECs, and MYC markedly accelerated the development of tumors. Our
      PDAC model supports critical roles of KRAS mutations, inactivation of the p53 and
      p16-pRB pathways, active telomerase and MYC expression in pancreatic
      carcinogenesis and thus recapitulates many features of human PDAC development.
      The present system with reversible control of oncogene expression enabled de novo
      development of PDAC from quasinormal human tissues preformed subcutaneously in
      mice and might be applicable to carcinogenesis models in many organ sites. 

PMID- 24858379
TI  - Licochalcone A, a natural chalconoid isolated from Glycyrrhiza inflata root,
      induces apoptosis via Sp1 and Sp1 regulatory proteins in oral squamous cell
      carcinoma.
AB  - Licochalcone A (LCA), a chalconoid derived from root of Glycyrrhiza inflata, has
      been known to possess a wide range of biological functions such as antitumor,
      anti-angiogenesis, antiparasitic, anti-oxidant, antibacterial and anti
      inflammatory effects. However, the anticancer effects of LCA on oral squamous
      cell carcinoma (OSCC) have not been reported. Our data showed that LCA inhibited
      OSCC cell (HN22 and HSC4) growth in a concentration- and time-dependent manner.
      Mechanistically, it was mediated via downregulation of specificity protein 1
      (Sp1) expression and subsequent regulation of Sp1 downstream proteins such as
      p27, p21, cyclin D1, Mcl-1 and survivin. Here, we found that LCA caused apoptotic
      cell death in HSC4 and HN22 cells, as characterized by sub-G1 population, nuclear
      condensation, Annexin V staining, and multi-caspase activity and apoptotic
      regulatory proteins such as Bax, Bid, Bcl(-xl), caspase-3 and PARP. Consequently,
      this study strongly suggests that LCA induces apoptotic cell death of OSCC cells
      via downregulation of Sp1 expression, prompting its potential use for the
      treatment of human OSCC.

PMID- 24858380
TI  - Prospective study of the cementless "New Wave" total knee mobile-bearing
      arthroplasty: 8-year follow-up.
AB  - One of the main factors affecting the survival of a total knee arthroplasty (TKA)
      is the fixation method. The constraints placed on the bone-implant interface of a
      mobile-bearing TKA must be taken in account during the design and evaluation
      phases. For more than two decades, calcium phosphate ceramics, particularly
      hydroxyapatitis, have been used in Europe to accelerate the bone integration of
      cementless implants. A prospective study of patients continuously recruited by
      three senior surgeons at three French private hospitals has been carried out.
      There were no exclusion criteria. Eighty-four (84) cementless mobile-bearing
      total knee prosthesis of the brand "New Wave" were implanted in 74 patients over
      a 2-year period (2004-2005). Implant survival at 8 years was 95% [with a
      confidence interval of 95%: 80.2-96.4%] when revision for any cause was defined
      as the endpoint. Five implants required surgical revision to exchange all or part
      of the implant: two for aseptic loosening of tibial component, one for
      osteolysis, one for persistent flessum (30 degrees ) and one for tibial
      periprosthetic fracture. Completely integrated implants and event-free outcomes
      were recorded in 91.4% of the cases at eight-year follow-up. The Hospital for
      Special Surgery score significantly improved from 56.8/100 points before the
      surgery to 83.9/100 points at the last follow-up (p < 0.05). Radiologically, only
      one patient had radiolucent lines around the tibial and femoral components. This
      cementless total knee prosthesis yielded good medium-term survival. Cementless
      arthroplasty can generate solid and durable bone fixation in this total weight
      bearing implant, and it seems that the hidroxyapathitis surface in this series
      stimulate the bone integration at the bone-implant interface.

PMID- 24858381
TI  - Phyto-liposomes as nanoshuttles for water-insoluble silybin-phospholipid complex.
AB  - Among various phospholipid-mediated drug delivery systems (DDS) suitable for
      topic and oral administration, phytosome technology represents an advanced
      innovation, widely used to incorporate standardized bioactive polyphenolic
      phytoconstituents into phospholipid molecular complexes. In order to extend their
      potential therapeutic efficiency also to other routes of administration, we
      proposed a novel phytosome carrier-mediated vesicular system (phyto-liposome) as
      DDS for the flavonolignan silybin (SIL), a natural compound with multiple
      biological activities related to its hepatoprotective, anticancer and antioxidant
      (radical scavenging) effects. We screened the optimum fraction of its phytosome,
      available in the market as SiliphosTM, into liposomes prepared by extrusion, such
      that vesicle sizes and charges, monitored through dynamic light scattering and
      laser doppler velocimetry, satisfied several quality requirements. Special
      emphasis was placed on the study of host-guest interaction by performing UV-vis
      absorption, spectrofluorimetry and NMR experiments both in aqueous and non-polar
      solvents to probe the effect of the presence of phospholipids on the electronic
      properties of SIL and its propensity to engage H bonding with the lipid headpolar
      groups. Finally, fluorescence microscopy observations confirmed the ability of
      phyto-liposomes to be internalized in human hepatoma cells, which was promising
      for their potential application in the treatment of acute or chronic liver
      diseases. 

PMID- 24858382
TI  - Surface charge switching nanoparticles for magnetic resonance imaging.
AB  - In this study, polypeptide-based nanoparticles [constituted using poly(L-lysine)
      coupled with deoxycholic acid (DOCA) and conjugated with 2,3-dimethylmaleic acid
      (DMA)] have high tumor selectivity once electrostatically switched by the acidic
      milieu of solid tumors. These nanoparticles exhibited a significantly increased
      in vitro cellular uptake and high accumulation in the acidic tumor site in vivo.
      Consequently, Fe3O4-loaded nanoparticles enabled high contrast magnetic resonance
      (MR) imaging of the tumor in vivo.

PMID- 24858383
TI  - Lipid nanocapsules for transdermal delivery of ropivacaine: in vitro and in vivo
      evaluation.
AB  - The objective of this research was to develop novel ropivacaine-loaded lipid
      nanocapsules (RPV-LNCs) and evaluate the potential of RPV-LNCs as external
      preparation for transdermal delivery. RPV-LNCs were prepared by phase inversion
      technique and optimized by response surface design. The permeation ability of RPV
      LNCs was characterized both in vitro and in vivo. The results showed that the
      optimized RPV-LNCs represented typical core-shell structure with the mean
      diameter of 62.1+/-1.7 nm. The entrapment efficiency and drug loading were 92.6+/
      1.3% and 1.35+/-0.20%, respectively. Moreover, the cumulative amount of RPV
      penetrated through excised skin from LNCs was 2.17 folds than that of the
      propylene glycol. In vivo, RPV-LNCs contributed a higher RPV concentration in
      plasma (5.743 MUg/mL). The RPV retained within dermis was 27.9+/-5.2 MUg/mL for
      LNCs, obviously remarkable than that of the propylene glycol group (15.6+/-3.9
      MUg/mL). The skin histopathology study and scanning electron microscope (SEM)
      showed that interaction between LNCs and skin surface changed the apparent
      morphology of stratumcorneum and broke the close conjugation of corneocyte
      layers. All the detailed evidence showed that LNCs could provide a promising
      tuning as a transdermal delivery system of ropivacaine.

PMID- 24858384
TI  - The risk of hydroquinone and sunscreen over-absorption via photodamaged skin is
      not greater in senescent skin as compared to young skin: nude mouse as an animal
      model.
AB  - Intrinsic aging and photoaging modify skin structure and components, which
      subsequently change percutaneous absorption of topically applied permeants. The
      purpose of this study was to systematically evaluate drug/sunscreen permeation
      via young and senescent skin irradiated by ultraviolet (UV) light. Both young and
      senescent nude mice were subjected to UVA (10 J/cm(2)) and/or UVB radiation (175
      mJ/cm(2)). Physiological parameters, immunohistology, and immunoblotting were
      employed to examine the aged skin. Hydroquinone and sunscreen permeation was
      determined by in vitro Franz cell. In vivo skin absorption was documented using a
      hydrophilic dye, rhodamine 123 (log P=-0.4), as a permeant. UVA exposure induced
      cyclooxygenase (COX)-2 and terminal deoxynucleotidyl transferase dUTP nick end
      labeling (TUNEL) upregulation. Epidermal tight junction (TJ) were degraded by
      UVA. UVB increased transepidermal water loss (TEWL) from 13 to 24 g/m(2)/h.
      Hyperplasia and inflammation, but not loss of TJ, were also observed in UVB
      treated skin. UVA+UVB- and UVA-irradiated skin demonstrated similar changes in
      histology and biomarkers. UVA+UVB or UVA exposure increased hydroquinone flux
      five-fold. A negligible alteration of hydroquinone permeation was shown with UVB
      exposure. Hydroquinone exhibited a lower penetration through senescent skin than
      young skin. Both UVA and UVB produced enhancement of oxybenzone flux and skin
      uptake. However, the amount of increase was less than that of hydroquinone
      delivery. Photoaging did not augment skin absorption of sunscreens with higher
      lipophilicity, including avobenzone and ZnO. Exposure to UVA generally increased
      follicular entrance of these permeants, which showed two- to three-fold greater
      follicular uptake compared to the untreated group. Photoaging had less impact on
      drug/sunscreen absorption with more lipophilic permeants. Percutaneous absorption
      did not increase in skin subjected to both intrinsic and extrinsic aging.

PMID- 24858385
TI  - Multimeric grain-marked micelles for highly efficient photodynamic therapy and
      magnetic resonance imaging of tumors.
AB  - Multimeric grain-marked micelles consisting of an inner core micelle (for Fe3O4
      encapsulation) and outer multi-grain micelles (for chlorin e6 (Ce6, a model drug)
      encapsulation) were fabricated using a micelle-to-micelle conjugation method.
      Grain micelles (mono-thiol functionalized micelles) were chemically linked to the
      surface of the core micelle (multi-maleimide functionalized micelle). These
      micelles enable discrete compartments for Ce6 and iron oxide (Fe3O4) that enable
      a significantly increased in vivo photodynamic tumor inhibition while preserving
      high contrast magnetic resonance (MR) imaging of the tumor in vivo. 

PMID- 24858386
TI  - Study on intralymphatic-targeted hyaluronic acid-modified nanoliposome: influence
      of formulation factors on the lymphatic targeting.
AB  - In this study, hyaluronic acid-modified docetaxel-loaded liposomes were prepared
      to evaluate the lymphatic targeting after subcutaneous administration, and
      formulation factors affecting the lymphatic targeting were examined, including
      free hyaluronic acid, molecular weight, hyaluronic acid-density and particle
      diameter. The high molecular weight hyaluronic acid-modified docetaxel-loaded
      liposomes (HA-LPs) and low molecular weight hyaluronic acid-modified docetaxel
      loaded liposomes (LMWHA-LPs) were prepared via electrostatic attraction. The
      physicochemical properties and in vitro drug release were evaluated. The
      lymphatic drainage and the lymph node uptake were investigated by
      pharmacokinetics and distribution recovery of docetaxel in lymph nodes, injection
      site and plasma. The lymphatic targeting ability of optimized Cy7-loaded LMWHA
      LPs (LMWHA-LPs/Cy7) was evaluated by near-infrared fluorescence imaging
      technique. The result showed that HA-LPs and LMWHA-LPs with suitable and stable
      physicochemical properties could be used for in vivo lymphatic targeting studies.
      Hyaluronic acid-modified liposome significantly increased the docetaxel recovery
      in lymph nodes, and displayed higher AUC(0-24h) and longer retention time
      compared to unmodified liposomes in vivo. In contrast, the presence of free
      hyaluronic acid hindered the lymphatic drainage and increased the plasma-drug
      concentration. Importantly, LMWHA-modification improved lymphatic drainage and
      lymph node uptake of liposomes compared with HA-modification. And Lymph node
      uptake of LMWHA-LPs depended mainly on LMWHA-density instead of particle size.
      The results of in vivo imaging showed that LMWHA-LPs/Cy7 significantly located in
      the lymphatic system. And both DTX-loaded and Cy7-loaded LMWHA-LPs had similar
      and stable lymphatic target level. Our investigation showed that LMWHA-LPs were a
      highly promising lymphatic targeting carrier for chemotherapy drugs and
      diagnostic fluorescence agents.

PMID- 24858387
TI  - Enhanced cellular uptake and anti-proliferating effect of chitosan hydrochlorides
      modified genistein loaded NLC on human lens epithelial cells.
AB  - This study was attempted to increase the cellular uptake of developed genistein
      loaded nanostructured lipid carriers (NLC) into human lens epithelial (HLE) cells
      by chitosan hydrochlorides coatings when applied in post lens capsule (PCO)
      treatment, and to provide further understanding of the uptake and anti
      proliferation mechanisms inside. NLCs were produced using melt-emulsification
      method and were subsequently coated with chitosan hydrochlorides by adsorption.
      The uptake of various particle sizes were evaluated and visualized by confocal
      laser scanning microscopy (CLSM), showing a size-dependent manner. The uptake of
      NLC was proved to be endocytosed in an energy dependent and clathrin-mediated
      endocytosis to HLE cells by the decrease in uptake at lower temperature, when pre
      saturated by blank NLC and in the presence of NaN3 and sucrose. CH coating
      improved the uptake percentage of NLC irrespective of the particle size, without
      influencing the uptake mechanism. Cell apoptosis was tested using PI and Annexin
      V-FITC/PI staining, followed by flow cytometer analysis. Higher anti
      proliferation effect was observed for CH-NLC in inhibiting the growth of HLE
      cells by causing more apoptosis. Results above indicate that GEN-NLC surface
      modified by chitosan hydrochlorides could enhance the trans-cellular performance
      and anti-proliferating effect as PCO therapy. 

PMID- 24858388
TI  - Polyvinylpyrrolidone oral films of enrofloxacin: film characterization and drug
      release.
AB  - Enrofloxacin is a fluoroquinolone derivative used for treating urinary tract,
      respiratory and skin infections in animals. However, low solubility and low
      bioavailability prevented it from using on humans. Polyvinylpyrrolidone (PVP) is
      an inert, non toxic polymer with excellent hydrophilic properties, besides it can
      enhance bioavailability by forming drug polymer conjugates. With the aim of
      increasing solubility and bioavailability, enrofloxacin thin films were prepared
      using PVP as a polymer matrix. The obtained oral thin films exhibited excellent
      uniformity and mechanical properties. Swelling properties of the oral thin films
      revealed that the water uptake was enhanced by 21%. The surface pH has been found
      to be 6.8+/-0.1 indicating that these films will not cause any irritation to oral
      mucosa. FTIR data of the oral thin films indicated physical interaction between
      drug and polymer. SEM analysis revealed uniform distribution of drug in polymer
      matrix. In vitro drug release profiles showed enhanced release profiles (which
      are also pH dependant) for thin films compared to pure drug. Antibacterial
      activity was found to be dose dependent and maximum susceptibility was found on
      Klebsiella pneumonia making this preparation more suitable for respiratory
      infections. 

PMID- 24858389
TI  - Development and evaluation of liquid embolic agents based on liquid crystalline
      material of glyceryl monooleate.
AB  - New type of liquid embolic agents based on a liquid crystalline material of
      glyceryl monooleate (GMO) was developed and evaluated in this study. Ternary
      phase diagram of GMO, water and ethanol was constructed and three isotropic
      liquids (ILs, GMO:ethanol:water=49:21:30, 60:20:20 and 72:18:10 (w/w/w)) were
      selected as potential liquid embolic agents, which could spontaneously form
      viscous gel cast when contacting with water or physiological fluid. The ILs
      exhibited excellent microcatheter deliverability due to low viscosity, and were
      proved to successfully block the saline flow when performed in a device to
      simulate embolization in vitro. The ILs also showed good cytocompatibility on
      L929 mouse fibroblast cell line. The embolization of ILs to rabbit kidneys was
      performed successfully under monitoring of digital subtraction angiography (DSA),
      and embolic degree was affected by the initial formulation composition and used
      volume. At 5th week after embolization, DSA and computed tomography (CT)
      confirmed the renal arteries embolized with IL did not recanalize in follow-up
      period, and an obvious atrophy of the embolized kidney was observed. Therefore,
      the GMO-based liquid embolic agents showed feasible and effective to embolize,
      and potential use in clinical interventional embolization therapy. 

PMID- 24858390
TI  - Optimizing surfactant content to improve oral bioavailability of ibuprofen in
      microemulsions: just enough or more than enough?
AB  - Microemulsions show excellent potential as drug delivery systems, but the
      surfactants used to prepare them can cause side effects. Researchers have
      explored various strategies to expand microemulsion area and thereby reduce the
      surfactant content necessary, but how these strategies affect drug oral
      bioavailability has not been investigated in detail. Microemulsions were prepared
      using 16% or 24% mixed surfactant Tween 80-Cremophor EL-PEG400 (1:1:2) and either
      6% caprylic/capric triglyceride oil (GTCC) or 6% or 15% mixed oil (MaisineTM 35-1
      with GTCC). Some microemulsions contained just enough surfactant based on ternary
      phase diagrams, while others had excess surfactant. All empty and ibuprofen
      loaded microemulsions were clear or translucent with a slight blue color, and
      they remained stable after dilution and centrifugation. In experiments with rats,
      oral bioavailability (AUC0?t) of ibuprofen in the microemulsions was similar for
      the different formulations (6779.0-7413.3 min MUg/mL) and significantly higher
      than that of an ibuprofen suspension (4830.9 min MUg/mL). The different
      formulations behaved similarly in a cellular uptake assay with Caco-2 cells.
      These results suggest that excess surfactant does not increase oral
      bioavailability or cellular uptake of ibuprofen. Therefore, to minimize side
      effects, using just enough surfactant to ensure microemulsion stability and drug
      solubility may be an appropriate strategy.

PMID- 24858391
TI  - Free paclitaxel loaded PEGylated-paclitaxel nanoparticles: preparation and
      comparison with other paclitaxel systems in vitro and in vivo.
AB  - Previously, PEGylated paclitaxel (PEG-PTX) was found not favorable as a polymer
      prodrug because of its poor antitumor efficiency. But surprisingly, it was found
      in our study that PEG-PTX could form a novel nanoparticle system with free PTX.
      To address how this system works, we compared PTX loaded PEG-PTX nanoparticles
      (PEG-PTX/PTX) with PTX loaded PEG-PLA micelles (PEG-PLA/PTX) or PTX injection
      available (Taxol((r))) in vitro and in vivo. Firstly, it was found that PEG
      PTX/PTX was more stable in aqueous solution than PEG-PLA/PTX in terms of PTX
      crystal formation and drug release. Then it was demonstrated that coumarin loaded
      PEG-PTX nanoparticles had a much higher uptake in MCF-7 cells compared to
      coumarin loaded PEG-PLA micelles. The in vivo imaging study revealed that DIR or
      DID (near infrared fluorescent substances) loaded PEG-PTX nanoparticles
      distributed more in tumors in MCF-7 tumor bearing mice than DIR or DID loaded PEG
      PLA micelles and solvent system of Taxol((r)). In the efficacy study with MCF-7
      tumor bearing mice, PEG-PTX/PTX showed significantly higher antitumor activity
      than PEG-PLA/PTX at the same PTX dosage. At the dose of 10mg free PTX per kg, PEG
      PTX/PTX displayed similar efficacy as Taxol((r)) but less toxicity evaluated by
      the loss of body weight. With the increase of free PTX to 15 mg/kg, PEG-PTX/PTX
      showed significantly better efficacy than Taxol((r)). In conclusion, with
      favorable characteristics in stability, cellular uptake, cytotoxicity,
      biodistribution, safety and efficacy, PEG-PTX/PTX seems highly potential as a
      nanocarrier for PTX delivery.

PMID- 24858392
TI  - Asian gastric cancer patients show superior survival: the experiences of a single
      Australian center.
AB  - BACKGROUND: Survival after curative gastrectomy for gastric cancer varies
      depending on region. The 5-year survival rates in Western trials reach 36-47%
      compared with 40-60% in Japanese studies. We analyzed the outcomes of Asian and
      non-Asian patients at a single Australian institution. METHODS: We analyzed a
      prospectively kept database of patients following gastric resection between 1994
      and 2010 at a tertiary Australian hospital. Overall survival was the primary
      endpoint. RESULTS: A total of 160 patients underwent a R0 gastrectomy with
      curative intent, of whom 26 (16%) were of Asian descent. Asian patients had a
      significantly younger age at diagnosis (60 +/- 16 vs. 70 +/- 11, p < 0.05) and
      longer overall survival (log-rank p = 0.018). Poor prognostic factors common to
      both groups included increased tumor length, higher T-score, higher LN ratio,
      poor tumor differentiation, and the presence of perineural or perivascular
      invasion. Multivariate analysis showed that non-Asian patients, higher T-score,
      higher N-score, and perivascular involvement were all independent predictors of
      poorer outcome. CONCLUSIONS: This study shows superior overall survival in Asian
      patients despite similar clinicopathological and treatment data. The younger age
      at diagnosis in Asian patients may suggest a different disease process between
      ethnicities. Targeted therapies based on population-specific tumor biology may
      potentially be beneficial.

PMID- 24858393
TI  - HIV testing behaviors and attitudes among community recruited methamphetamine
      users in a South African township.
AB  - Methamphetamine users in South Africa are at high risk for HIV infection and
      transmission, but little is known about HIV testing in this population. We
      examined HIV testing behaviors and attitudes in 362 methamphetamine users
      recruited using chain referral sampling from one peri-urban community. Many (44
      %) had not been HIV tested in the past year. HIV testing was associated with
      positive testing attitudes, less AIDS stigma, and greater methamphetamine stigma.
      Among participants who reported HIV infection (8 %), less than half were linked
      to care. Findings highlight the need to identify barriers to HIV service uptake
      for methamphetamine users.

PMID- 24858394
TI  - Sexual partner notification of HIV infection among a National United States-based
      sample of HIV-infected men.
AB  - Limited data exist on whether sexual partner notification practices among HIV
      infected men, particularly those who have sex with men (MSM), vary by HIV viral
      load. We examined factors associated with complete (all partners) versus
      incomplete partner notification in 760 HIV-infected individuals across the United
      States, 49 % of whom were MSM. Thirty-four percent reported incomplete partner
      notification. Incomplete partner notification was more likely among black men,
      MSM, and those reporting casual partners and non-condom use. Partner notification
      practices did not vary by HIV viral load except among those with casual partners
      in whom a detectable viral load was associated with incomplete partner
      notification. Increased sexual partner notification among HIV-infected men,
      especially MSM, is needed.

PMID- 24858395
TI  - Genetic response of Paspalum plicatulum to genome duplication.
AB  - Paspalum plicatulum is a perennial rhizomatous grass with natural diploid and
      polyploid cytotypes. In this study, we investigated the occurrence of sequence
      polymorphisms arising immediately after genome autoduplication in this species.
      Two mixoploid plants (4C and 7D) were previously obtained through colchicine
      treatment of seeds generated by open pollination of a diploid plant (H14-2x).
      Diploid and tetraploid sectors from both mixoploids were dissected to generate
      two ploidy series (4C-2x/4C-4x and 7D-2x/7D-4x). Molecular fingerprints were
      generated from the maternal plant H14-2x, both ploidy series (4C-2x/4C-4x and 7D
      2x/7D-4x), and a tetraploid plant (C1) produced by selfing 7D-4x. Our results
      indicate that immediately after polyploidization P. plicatulum suffers genetic
      rearrangements affecting ~28-38 % of the genome. Band gain and loss were equally
      prevalent at a statistically significant level. At least 5.62 % of the genome
      experimented recurrent genetic variation in a non-random basis with a confidence
      of 94.88 %. A significant proportion of novel bands (36 out of 195; 18.4 %) was
      detected in the C1 tetraploid plant. Half of these bands were not amplified in
      either H14-2x or 7D-4x, while the remainders were present in H14-2x but absent in
      7D-4x. Our results indicate the occurrence of a considerable number of genetic
      changes in P. plicatulum immediately after polyploidization, some of which were
      recurrently detected in different independent events. Moreover, we confirmed that
      after polyploidization, lost ancestral alleles were spontaneously recovered in
      further generations, a phenomenon previously reported by other research groups.

PMID- 24858396
TI  - Stabilization of HAC1 influenza vaccine by spray drying: formulation development
      and process scale-up.
AB  - PURPOSE: Stable vaccines with long shelf lives and reduced dependency on the cold
      chain are ideal for stockpiling and rapid deployment during public emergencies,
      including pandemics. Spray drying is a low-cost process that has potential to
      produce vaccines stable at a wide range of temperatures. Our aim was to develop a
      stable formulation of a recombinant H1N1 influenza hemagglutinin vaccine
      candidate and take it to pilot-scale spray-drying production. METHODS: Eight
      formulations containing different excipients were produced and assayed for
      antigen stability, powder characteristics, and immunogenicity after storage at a
      range of temperatures, resulting in the identification of four promising
      candidates. A pilot-scale spray-drying process was then developed for further
      testing of one formulation. RESULTS: The pilot-scale process was used to
      reproducibly manufacture three batches of the selected formulation with yields
      >90%. All batches had stable physical properties and in vitro potency for 6
      months at temperatures from -20 degrees C to +50 degrees C. Formulations stored
      for 3 months elicited immunogenic responses in mice equivalent to a frozen lot of
      bulk vaccine used as a stability control. CONCLUSIONS: This study demonstrates
      the feasibility of stabilizing subunit vaccines using a spray-drying process and
      the suitability of the process for manufacturing a candidate product.

PMID- 24858397
TI  - Folate and TAT peptide co-modified liposomes exhibit receptor-dependent highly
      efficient intracellular transport of payload in vitro and in vivo.
AB  - PURPOSE: Using different chain lengths of PEG as linkers to develop a novel
      folate (FA) and TAT peptide co-modified doxorubicin (DOX)-loaded liposome (FA/TAT
      LP-DOX) and evaluate its potential for tumor targeted intracellular drug
      delivery. METHODS: FA/TAT-LP-DOX was prepared by pH gradient method and post
      insertion method and the optimal ligand density was screened by MTT assay. In
      vitro evaluation was systematically performed through cytotoxicity assay,
      cellular uptake studies, subcellular localization and cellular uptake mechanism
      in folate receptor (FR) over-expressing KB tumor cells. In vivo tumor targeted
      delivery of FA/TAT-LP-DOX was also studied by in vivo fluorescence imaging in a
      murine KB xenograft model. RESULTS: The particle size and zeta potential
      determination indicated that FA and TAT were successfully inserted into the
      liposome and cationic TAT peptide was completely shielded. With the optimal
      ligand density (5% of FA and 2.5% TAT), the FA/TAT-LP-DOX exhibited improved
      cytotoxity and cellular uptake efficiency compared with its single-ligand
      counterparts (FA-LP-DOX and PEG/TAT-LP-DOX). Competitive inhibition and uptake
      mechanism experiments revealed that FA and TAT peptide played a synergistic
      effect in facilitating intracellular transport of the liposome, and association
      between FA and FA receptors activated this transport process. In vivo imaging
      further demonstrated the superiority of FA/TAT-LP in tumor targeting and
      accumulation. CONCLUSIONS: Folate and TAT peptide co-modified liposome using
      different chain lengths of PEG as linkers may provide a useful strategy for
      specific and efficient intracellular drug delivery.

PMID- 24858398
TI  - Chitosan-based hybrid nanocomplex for siRNA delivery and its application for
      cancer therapy.
AB  - PURPOSE: Chitosan, a natural and biocompatible cationic polymer, is an attractive
      carrier for small interfering RNA (siRNA) delivery. The purpose of this study was
      to develop a chitosan-based hybrid nanocomplex that exhibits enhanced physical
      stability in the bloodstream compared with conventional chitosan complexes.
      Hybrid nanocomplexes composed of chitosan, protamine, lecithin, and thiamine
      pyrophosphate were prepared for systemic delivery of survivin (SVN) siRNA.
      METHODS: Physicochemical properties of the nanoparticles including mean diameters
      and zeta potentials were characterized, and target gene silencing and cellular
      uptake efficiencies of the siRNA nanocomplexes in prostate cancer cells (PC-3
      cells) were measured. In vivo tumor targetability and anti-tumor efficacy by
      systemic administration were assessed in a PC-3 tumor xenograft mouse model by
      near-infrared fluorescence (NIRF) imaging and tumor growth monitoring,
      respectively. RESULTS: Mean diameters of the SVN siRNA-loaded hybrid nanocomplex
      (GP-L-CT) were less than 200 nm with a positive zeta potential value in water and
      were maintained without aggregation in culture media and 50% fetal bovine serum.
      SVN expression in PC-3 cells was reduced to 21.9% after treating with GP-L-CT.
      The tumor targetability and growth inhibitory efficacies of GP-L-CT supported the
      use of this novel hybrid nanocomplex as a cancer therapeutic and as a theranostic
      system for systemic administration. CONCLUSIONS: A chitosan-based hybrid
      nanocomplex was successfully developed for the systemic delivery of SVN siRNA,
      which could serve as an alternative to cationic polymeric nanoparticles that are
      unstable in serum.

PMID- 24858399
TI  - Comparing ethylene glycol with glycerol and with or without dithiothreitol and
      sucrose for cryopreservation of bull semen in egg-yolk containing extenders.
AB  - There are few studies performed for investigating the roles of different ratio
      and cryoprotectants with dithiothreitol or sucrose on sperm motility
      characteristics and antioxidant capacities of post-thawed bull spermatozoa. The
      objectives of this study were to compare glycerol (G) and ethylene glycol (EG) at
      different concentrations as cryoprotectants and dithiothreitol (D) or sucrose (S)
      (with/without) as antioxidants in Tris extender for cryopreservation of bull
      semen. Twenty-four ejaculates obtained from three bulls were included in the
      study. Each ejaculate was split into four equal aliquots and diluted using both
      of the Tris extenders with glycerol (5% or 7%) or ethylene glycol (3% or 5%).
      After that, each extenders were split into three equal aliquots and diluted using
      both of the dithiothreitol 5mM or sucrose 25 mM, and control (without additives)
      was cooled to 4  degrees C and frozen in 0.25-ml French straws. when compared to
      control, different doses cryoprotectants and antioxidants addition no
      significantly increased the percentages of post-thaw sperm progressive and
      motitilities, acrosome abnormality and plasma membrane integrity (P>0.05).
      However, EG3+S yielded the greatest percentages of the total abnormality
      (P<0.05). As regard to antioxidant activities G7 and EG5 led to lowest MDA
      activity with or without D or S but, these results were not supported to the GPx
      activity (P<0.01). The sperm motion characteristics such as VAP, VCL, ALH and BCF
      gave significantly different results (P<0.05). When compared the DNA integrity,
      different doses cryoprotectants without antioxidants addition significantly
      increased the percentages of the tail intensity and tail moment (P<0.05). There
      were no significant differences observed in non-return rates among all treatment
      groups (P>0.05).

PMID- 24858400
TI  - Overexpression of SHP2 tyrosine phosphatase promotes the tumorigenesis of breast
      carcinoma.
AB  - Expression of Src homology phosphotyrosine phosphatase 2 (SHP2) has been observed
      in human breast cancer. SHP2 is known to promote cell migration and invasiveness.
      However, the pathophysiologic role of SHP2 and its relevance to tumorigenesis are
      still largely unknown. In the present study, we aimed to evaluate the effect of
      SHP2 on the malignant phenotype of human breast cancer. An SHP2-overexpressing
      human breast cancer cell line was established by stable transfection of the SHP2
      vector. The expression of SHP2 protein was detected using western blotting. The
      effects of SHP2 overexpression on cell proliferation were examined by an MTS
      assay. Invasion and migration abilities of the SHP2-overexpressing cells were
      determined using a Matrigel-based Boyden chamber invasion assay and a monolayer
      wound-healing assay. Increased SHP2 expression was detected following SHP2-vector
      transfection in the MDA-MB-231 cells. Overexpression of SHP2 was associated with
      increased cell proliferation and clone formation, and decreased chemotherapeutic
      sensitivity. Furthermore, transfection of SHP2 into breast cancer cells
      significantly promoted tumor growth in a mouse xenograft model. The mechanism of
      the promotion of tumorigenesis by SHP2 appears to involve its ability to increase
      the activity of ERK/AKT-mediated signaling pathways. In conclusion, our data
      suggest an important role of SHP2 in the molecular etiology of tumor growth, and
      implicate the potential application of SHP2 in cancer therapy.

PMID- 24858401
TI  - Risk factors of low vitamin D status in adolescent females in Kuwait:
      implications for high peak bone mass attainment.
AB  - Risks of low vitamin D status in Kuwaiti adolescent girls are high parathyroid
      hormone (PTH), high waist/hip ratio, veiling and not having a private room. Low
      vitamin D status is likely to have a negative impact on their bone mass and
      accrual. INTRODUCTION: Low serum 25-hydroxyvitamin D (25OHD) levels are
      repeatedly found in females in the Middle East, which is a cause for concern
      particularly for adolescent females. This is because vitamin D has been shown to
      promote bone mineral accrual in adolescence. PURPOSE: The aim of this study was
      to assess the risk factors of low vitamin D status in adolescent females and to
      assess its impact on their bone mass. METHODS: Serum 25OHD and PTH were measured
      in 232 females. Anthropometric measurements and skin colour were obtained. Bone
      measurements at the lumbar spine were performed using dual-energy x-ray
      absorptiometry (DXA). Data on food intake, physical activity (PA) and sun
      exposure were taken. Binary logistic regression was used to assess the risk
      factors of serum 25OHD levels <25 nmol/L and multiple linear regression was used
      to assess the predictors of bone mineral variables. RESULTS: Median 25OHD was
      19.4 nmol/L (IQR 16.4-23.68), among which 98.7 % obtained <50 nmol/L. PTH >7
      pmol/L (odds ratio (OR) 4.3; 95 % CI 1.8, 10.2), not having a private room (OR
      3.7; 95 % CI 1.4, 9.8), veiling (OR 2.4; 95 % CI 1.1, 5.5) and waist/hip ratio
      >0.75 (OR 2.1; 95 % CI 1.0, 4.3) were risk factors of low vitamin D status,
      whereas, height, weight, month since menarche, PTH, animal protein intake and PA
      were independent predictors of bone mineral content (p < 0.05). CONCLUSION: Low
      vitamin D status is prevalent in Kuwaiti adolescent females, which may have a
      negative impact on their bone mineralization and accrual. Further investigation
      is needed to reveal the underlying causes.

PMID- 24858402
TI  - Reproductive impacts and physiological adaptations of zebrafish to elevated
      dietary nickel.
AB  - Nickel (Ni) concentrations in the environment can rise due to human industrial
      activities. The toxicity of waterborne Ni to aquatic animals has been examined in
      a number of previous studies; however, little is known about the impacts of
      elevated dietary Ni. In the present study, zebrafish were chronically fed diets
      containing two concentrations of Ni [3.7 (control) and 116 MUg Ni/g diet]. Ni
      exposed males, but not females, were significantly smaller (26%) compared to
      controls at 80 days. In addition, total egg production was decreased by 65% in
      the Ni treatment at 75-78 days of the experiment. Ni was ubiquitously distributed
      in control animals (similar to previous studies), and concentrations varied
      between tissues by 15-fold. Ni exposure resulted in modest but significant Ni
      accumulation in some tissues (increases were highest in brain, vertebrae and gut;
      44%, 34% and 25%, respectively), an effect observed only at 80 days. The limited
      Ni accumulation may be due to (1) the lack of an acidified stomach in zebrafish
      and/or (2) the efficient upregulation of Ni transport and excretion mechanisms,
      as indicated by the 4.5-fold increase in waterborne (63)Ni uptake by Ni-exposed
      fish. Eggs from Ni-exposed adults had Ni concentrations that were 5.2-fold higher
      than controls. However, by 4 days post fertilization, larvae had similar Ni
      concentrations as controls, demonstrating a capacity for rapid Ni depuration.
      Larvae from Ni-exposed adults were also more resistant to waterborne Ni (35%
      increase in the 96-h LC50 over controls). In conclusion, elevated dietary Ni
      significantly affected zebrafish reproduction despite only modest tissue Ni
      accumulation. There were also indications of adaptation, including increased Ni
      uptake rates and increased Ni tolerance of offspring from Ni-exposed adults. Ni
      concentrations were particularly elevated in the brain with exposure; possible
      relations to growth and reproductive impacts require further study.

PMID- 24858403
TI  - Determination of small molecule ABAD inhibitors crossing blood-brain barrier and
      pharmacokinetics.
AB  - A major obstacle to the development of effective treatment of Alzheimer's disease
      (AD) is successfully delivery of drugs to the brain. We have previously
      identified a series of benzothiazole phosphonate compounds that block the
      interaction of amyloid-beta peptide with amyloid-beta binding alcohol
      dehydrogenase (ABAD). A selective and sensitive method for the presence of three
      new benzothiazole ABAD inhibitors in mouse plasma, brain, and artificial
      cerebrospinal fluid has been developed and validated based on high performance
      liquid chromatography tandem mass spectrometry. Mass spectra were generated using
      Micromass Quattro Ultima "triple" quadrupole mass spectrometer equipped with an
      Electrospray Ionization interface. Good linearity was obtained over a
      concentration range of 0.05-2.5 MUg/ml. The lowest limit of quantification and
      detection was found to be 0.05 MUg/ml. All inter-day accuracies and precisions
      were within +/- 15% of the nominal value and +/- 20%, respectively, at the lower
      limit of quantitation. The tested compounds were stable at various conditions
      with recoveries >90.0% (RSD <10%). The method used for pharmacokinetic studies of
      compounds in mouse cerebrospinal fluid, plasma, and brain is accurate, precise,
      and specific with no matrix effect. Pharmacokinetic data showed that these
      compounds penetrate the blood-brain barrier (BBB) yielding 4-50 ng/ml peak brain
      concentrations and 2 MUg/ml peak plasma concentrations from a 10 mg/kg dose.
      These results indicate that our newly synthesized small molecule ABAD inhibitors
      have a good drug properties with the ability to cross the blood-brain barrier,
      which holds a great potential for AD therapy. 

PMID- 24858404
TI  - Modulation of the AMPK/Sirt1 axis during neuronal infection by herpes simplex
      virus type 1.
AB  - Currently, it is unclear whether a neuron that undergoes viral reactivation and
      produces infectious particles survives and resumes latency or is killed, which is
      intriguing even if still unanswered. Previous reports have shown that herpes
      simplex virus type 1 (HSV-1) inhibits apoptosis during early infection, but is
      pro-apoptotic during productive infection. Taking in consideration that the
      stress sensors AMPK and Sirt1 are involved in neuronal survival and
      neuroprotection, we hypothesized that HSV-1 could activate the AMPK/Sirt1 axis as
      a strategy to establish latency through inhibition of apoptosis and restoration
      of the energy status. These effects could be accomplished through deacetylation
      of pro-apoptotic protein p53 and regulation of the master regulator of
      mitochondrial biogenesis and function PGC-1alpha and its target gene TFAM.
      Accordingly, we evaluated the AMPK/Sirt1 axis and its targets p53, PGC-1alpha,
      and acetyl CoA carboxylase in mice neuronal cultures infected with HSV-1 by
      western blot, RT-qPCR, and immunofluorescence analyses. Herein, we show that HSV
      1 differentially modulates the AMPK/Sirt1 axis during the course of infection. In
      fact, during early infection (2 hpi) activated AMPK (p-AMPK) was down-regulated,
      but thereafter recovered gradually. In contrast, the levels of acetylated-p53
      increased during the first hours post infection, but afterwards were reduced in
      parallel with the activation of Sirt1. However, acetylated-p53 peaked again at 18
      hpi during productive infection, suggesting an activation of apoptosis.
      Strikingly, acetylated-p53, Sirt1, and p-AMPK apparently translocate from the
      nucleus to the cytoplasm after 4 hpi, where they accumulate in discrete foci in
      the perinuclear region. These results suggest that HSV-1 modulates the AMPK/Sirt1
      axis differentially during the course of infection interfering with pro-apoptotic
      signaling and regulating mitochondrial biogenesis. 

PMID- 24858405
TI  - The pancreas-brain axis: insight into disrupted mechanisms associating type 2
      diabetes and Alzheimer's disease.
AB  - Epidemiological and observational studies indicate a positive correlation between
      type 2 diabetes (T2DM) and dementia, with an increased risk of dementia and
      Alzheimer's disease (AD) associated with insulin-treated diabetes patients. The
      purpose of this review is to reveal the molecular mechanisms that connect
      physiological and pathological processes commonly observed in T2DM and AD.
      Conformational modifications in peptide residues, such as amyloid-beta peptide in
      AD and amylin in T2DM have been shown to instigate formation of insoluble protein
      aggregates that get deposited in extracellular spaces of brain and pancreatic
      tissue thus disrupting their normal function. Impaired insulin signaling plays a
      critical role in AD pathogenesis by reducing IRS-associated PI3 kinase activity
      and increasing GSK-3beta activity. GSK-3beta has been suggested to be a component
      of the gamma-secretase complex and is involved in amyloid-beta protein precursor
      processing. GSK-3beta along with CDK5 is responsible for hyperphosphorylation of
      tau leading to the formation of neurofibrillary tangles. In summary, there is
      evidence to believe that a molecular link connects AD and T2DM and has potential
      for further investigation toward development of an effective therapeutic target. 

PMID- 24858406
TI  - A strategy for co-analysis of microRNAs and DNA.
AB  - MicroRNAs (miRNAs, 18-25 bases in length) are small, non-coding RNAs that
      regulate gene expression at the post-transcriptional level. The small size makes
      them more stable than conventional mRNA as a biomarker identifying body fluids in
      degraded or compromised samples. Compared to mRNA, however, due to the very short
      length of miRNAs, it is a challenge to design proper primers to achieve
      miRNAs/DNA co-extraction and co-analysis. Here we describe the design of a
      specific linear RT primer for the reverse transcription reaction and a pair of
      PCR primers to be used in the endpoint PCR reaction for each miRNA marker, and
      presented a strategy for co-analysis of a set of miRNAs and DNA on the same
      extract using the same detection platform. A set of 4 miRNA markers (miR214 as
      menstrual blood marker, miR451a as venous blood marker, miR888 and miR891a as
      semen markers) and a DNA STR multiplex kit were co-analyzed by capillary
      electrophoresis. The result demonstrated that the strategy of co-analysis of
      miRNAs/DNA could not only identify the body fluid, but also obtain a STR profile
      for the same sample. 

PMID- 24858408
TI  - Purification of Alaskan walleye pollock (Gadus chalcogrammus) and New Zealand
      hoki (Macruronus novaezelandiae) liver oil using short path distillation.
AB  - The beneficial health effects of a diet rich in n-3 long chain polyunsaturated
      fatty acids (n-3 LC-PUFA) have been extensively researched in recent years.
      Marine oils are an important dietary source of n-3 LC-PUFA, being especially rich
      in two of the most important fatty acids of this class, EPA (eicosapentaenoic
      acid; 20:5n-3) and DHA (docosahexaenoic acid; 22:6n-3). Oils rich in n-3 LC-PUFA
      are prone to oxidation that leads to loss of product quality. Alaskan pollock
      (Gadus chalcogrammus Pallas, 1814) and New Zealand's hoki (Macruronus
      novaezelandiae Hector, 1871) are the highest volume fisheries of their respective
      countries. Both produce large quantities of fishery byproducts, in particular
      crude or unrefined n-3 LC-PUFA containing oils. Presently these oils are used as
      ingredients for animal feed, and only limited quantities are used as human
      nutritional products. The aim of this research was to investigate the
      applicability of short path distillation for the purification of pollock and hoki
      oil to produce purified human-grade fish oil to meet quality specifications.
      Pollock and hoki oils were subjected to short path distillation and a significant
      decrease in free fatty acids and lipid oxidation (peroxide and para-anisidine
      values) products was observed. Purified oils met the Global Organization for EPA
      and DHA Omega-3 (GOED) standard for edible fish oils. 

PMID- 24858407
TI  - DHA-containing oilseed: a timely solution for the sustainability issues
      surrounding fish oil sources of the health-benefitting long-chain omega-3 oils.
AB  - Benefits of long-chain (>=C20) omega-3 oils (LC omega-3 oils) for reduction of
      the risk of a range of disorders are well documented. The benefits result from
      eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA); optimal intake levels
      of these bioactive fatty acids for maintenance of normal health and prevention of
      diseases have been developed and adopted by national and international health
      agencies and science bodies. These developments have led to increased consumer
      demand for LC omega-3 oils and, coupled with increasing global population, will
      impact on future sustainable supply of fish. Seafood supply from aquaculture has
      risen over the past decades and it relies on harvest of wild catch fisheries also
      for its fish oil needs. Alternate sources of LC omega-3 oils are being pursued,
      including genetically modified soybean rich in shorter-chain stearidonic acid
      (SDA, 18:4omega3). However, neither oils from traditional oilseeds such as
      linseed, nor the SDA soybean oil have shown efficient conversion to DHA. A recent
      breakthrough has seen the demonstration of a land plant-based oil enriched in
      DHA, and with omega-6 PUFA levels close to that occurring in marine sources of
      EPA and DHA. We review alternative sources of DHA supply with emphasis on the
      need for land plant oils containing EPA and DHA. 

PMID- 24858409
TI  - Toxicity mechanisms of the food contaminant citrinin: application of a
      quantitative yeast model.
AB  - Mycotoxins are important food contaminants and a serious threat for human
      nutrition. However, in many cases the mechanisms of toxicity for this diverse
      group of metabolites are poorly understood. Here we apply live cell gene
      expression reporters in yeast as a quantitative model to unravel the cellular
      defense mechanisms in response to the mycotoxin citrinin. We find that citrinin
      triggers a fast and dose dependent activation of stress responsive promoters such
      as GRE2 or SOD2. More specifically, oxidative stress responsive pathways via the
      transcription factors Yap1 and Skn7 are critically implied in the response to
      citrinin. Additionally, genes in various multidrug resistance transport systems
      are functionally involved in the resistance to citrinin. Our study identifies the
      antioxidant defense as a major physiological response in the case of citrinin. In
      general, our results show that the use of live cell gene expression reporters in
      yeast are a powerful tool to identify toxicity targets and detoxification
      mechanisms of a broad range of food contaminants relevant for human nutrition. 

PMID- 24858410
TI  - Morphological and molecular changes of human granulosa cells exposed to 5
      azacytidine and addressed toward muscular differentiation.
AB  - Converting adult cells from one cell type to another is a particularly
      interesting idea for regenerative medicine. Terminally differentiated cells can
      be induced to de-differentiate in vitro to become multipotent progenitors. In
      mammals these changes do not occur naturally, however exposing differentiated
      adult cells to synthetic molecules capable of selectively reverting cells from
      their lineage commitment to a more plastic state makes it possible to re-address
      their fate. Only scattered information are available on the morphological changes
      and ultrastructural remodeling taking place when cells convert into a different
      and specific type. To better clarify these aspects, we derived human granulosa
      cell (GC) primary cultures and analyzed the morphological changes taking place in
      response to the exposure to the epigenetic modifier 5-azacytidine (5-aza-CR) and
      to the treatment with VEGF, as a stimulus for inducing differentiation into
      muscle cells. Ultrastructural modifications and molecular marker expression were
      analyzed at different intervals during the treatments. Our results indicate that
      the temporary up regulation of pluripotency markers is accompanied by the loss of
      GC-specific ultrastructural features, mainly through autophagocitosis, and is
      associated with a temporary chromatin decondensation. After exposure to VEGF the
      induction of muscle specific genes was combined with the appearance of
      multinucleated cells with a considerable quantity of non-spatially organized
      filaments. The detailed analysis of the morphological changes occurring in cells
      undergoing lineage re-addressing allows a better understanding of these process
      and may prove useful for refining the use of somatic cells in regenerative
      medicine and tissue replacement therapies. 

PMID- 24858411
TI  - Balloon-occluded retrograde transvenous obliteration versus endoscopic injection
      sclerotherapy for isolated gastric varices: a comparative study.
AB  - Isolated gastric varices (IGV) have a lower risk of bleeding than esophageal
      varices, however IGV bleeding is associated with a higher mortality than bleeding
      of esophageal varices. In recent years, two widely used treatments for IGV have
      been balloon-occluded retrograde transvenous obliteration (B-RTO) and endoscopic
      injection sclerotherapy (EIS) using cyanoacrylate or ethanolamine oleate (EO).
      This study compared these two treatment methods for IGV. The subjects were 112
      patients who were treated at our hospital for IGV bleeding between October 1990
      and December 2003. Forty-nine (49) patients were treated with B-RTO and 63
      patients with EIS. These two patient groups were compared as regards content of
      treatment, post-treatment incidence of variceal bleeding, incidence of IGV
      rebleeding, survival rate, cause of death, and complications. Multivariate
      analysis was performed on post-treatment variceal bleeding and survival. Although
      EO was used in higher amounts in the B-RTO group than in the EIS group, the B-RTO
      group had a significantly lower number of treatment sessions and a significantly
      shorter treatment period (p<0.05). The EIS group had significantly more patients
      with IGV rebleeding after treatment than the B-RTO group. Treatment method was
      the only independent prognostic factor of IGV bleeding after treatment (p=0.024).
      The two groups did not differ significantly in the percentage of patients with
      aggravated esophageal varices after treatment. Bleeding from ectopic varices was
      not observed in any patient. There was no significant difference in survival by
      treatment method. The presence of hepatocellular carcinoma was the only
      independent prognostic factor for survival (p=0.003). It is concluded that B-RTO
      was more effective than EIS in the eradication of IGV and prevention of IGV
      recurrence and rebleeding. 

PMID- 24858412
TI  - Association between thromboembolic events and the JAK2 V617F mutation in
      myeloproliferative neoplasms.
AB  - Thrombotic complications are a major cause of death in patients with Philadelphia
      chromosome-negative myeloproliferative neoplasms (MPNs), which are closely
      associated with the JAK2 V617F activating mutation. However, whether the presence
      of the JAK2 V617F mutation affects thrombotic risk is currently unknown, although
      some reports have suggested a variable association with thrombosis. Therefore, we
      investigated the association between JAK2 V617F and various complications,
      including thrombosis, in Japanese patients with MPNs. We assessed the JAK2 V617F
      status in 140 patients who were diagnosed or doubted as having some type of MPN
      by utilizing a JAK2 V617F-specific guanine-quenching probe. JAK2 V617F was
      detected in 31 of 51 patients (60.8%) with essential thrombocythemia, all 16
      patients (100%) with polycythemia vera, 4 of 11 patients (36.4%) with primary
      myelofibrosis, 2 of 18 patients (11.1%) with other types of MPNs, and none of the
      44 patients with doubted MPN. In the 78 patients with classical MPN, JAK2 V617F
      correlated with a leukocyte count >=10,000/MUl (p=0.046). Complications of
      thrombosis, hemorrhage, and leukemic transformation occurred in 21 (41.2%), 4
      (25.0%), and 3 (27.3%) patients with classical MPN, respectively, and thrombotic
      events (TE) occurred more frequently in patients with JAK2 V617F than without
      (p=0.047). Based on these findings, initial screening for the JAK2 mutation and
      careful monitoring for thrombotic events should be performed in patients with
      MPN. 

PMID- 24858413
TI  - Production of ghrelin by the stomach of patients with gastric cancer.
AB  - Poor nutrition and weight loss are important factors contributing to poor quality
      of life (QOL) after gastrectomy in patients with gastric cancer. Ghrelin is a
      hormone produced by the stomach that, plays a role in appetite increase and fat
      storage. The present study aims to clarify the location of ghrelin mRNA in the
      stomach, changes in blood ghrelin concentrations after gastrectomy and whether or
      not they are associated with the reconstruction method in patients with gastric
      cancer. We collected seven normal mucosa samples from different parts of six
      totally resected stomachs with gastric cancer. We extracted RNA from the normal
      mucosa, synthesized cDNA from total RNA (1 MUg), and then quantified ghrelin mRNA
      using quantitative real-time polymerase chain reaction (Q-PCR). Ghrelin blood
      concentrations were measured using enzyme-linked immunosorbent assay (ELISA) kits
      in 74 patients with gastric cancer (total gastrectomy (TG), n=23; distal
      gastrectomy (DG), n=30; proximal gastrectomy (PG), n=11; pylorus preserving
      gastrectomy (PPG), n=10). In order, the ghrelin gene was expressed most
      frequently in the gastric body, followed by the fornix, cardia, antrum and
      pylorus ring. Blood ghrelin concentrations after surgery similarly changed in all
      groups. The average blood ghrelin concentrations were significantly higher in the
      DG and PPG groups than in the TG group on postoperative days (POD) 1, 7, 30, 90
      and 180. However, blood ghrelin concentrations did not significantly differ
      between the DG and TG groups on POD 270 and 360. Cells that produce ghrelin are
      supposed to be located mostly in the fundic gland of the stomach. We speculate
      that the production of ghrelin from other organs increases from around nine
      months after total gastrectomy. Therefore, evaluating the nutritional status and
      the weight of patients at nine months after total gastrectomy is important to
      help these patients improve their QOL. 

PMID- 24858414
TI  - Biochemistry of high stearic sunflower, a new source of saturated fats.
AB  - Fats based on stearic acid could be a healthier alternative to existing oils
      especially hydrogenated fractions of oils or palm, but only a few non-tropical
      species produce oils with these characteristics. In this regard, newly developed
      high stearic oil seed crops could be a future source of fats and hard stocks rich
      in stearic and oleic fatty acids. These oil crops have been obtained either by
      breeding and mutagenesis or by suppression of desaturases using RNA interference.
      The present review depicts the molecular and biochemical bases for the
      accumulation of stearic acid in sunflower. Moreover, aspects limiting the
      accumulation of stearate in the seeds of this species are reviewed. This included
      data obtained from the characterization of genes and enzymes related to fatty
      acid biosynthesis and triacylglycerol assembly. Future improvements and uses of
      these oils are also discussed. 

PMID- 24858415
TI  - Cell cycle progression in response to oxygen levels.
AB  - Hypoxia' or decreases in oxygen availability' results in the activation of a
      number of different responses at both the whole organism and the cellular level.
      These responses include drastic changes in gene expression, which allow the
      organism (or cell) to cope efficiently with the stresses associated with the
      hypoxic insult. A major breakthrough in the understanding of the cellular
      response to hypoxia was the discovery of a hypoxia sensitive family of
      transcription factors known as the hypoxia inducible factors (HIFs). The hypoxia
      response mounted by the HIFs promotes cell survival and energy conservation. As
      such, this response has to deal with important cellular process such as cell
      division. In this review, the integration of oxygen sensing with the cell cycle
      will be discussed. HIFs, as well as other components of the hypoxia pathway, can
      influence cell cycle progression. The role of HIF and the cell molecular oxygen
      sensors in the control of the cell cycle will be reviewed. 

PMID- 24858416
TI  - TRPM6 kinase activity regulates TRPM7 trafficking and inhibits cellular growth
      under hypomagnesic conditions.
AB  - The channel kinases TRPM6 and TRPM7 are both members of the melastatin-related
      transient receptor potential (TRPM) subfamily of ion channels and the only known
      fusions of an ion channel pore with a kinase domain. TRPM6 and TRPM7 form
      functional, tetrameric channel complexes at the plasma membrane by
      heteromerization. TRPM6 was previously shown to cross-phosphorylate TRPM7 on
      threonine residues, but not vice versa. Genetic studies demonstrated that TRPM6
      and TRPM7 fulfill non-redundant functions and that each channel contributes
      uniquely to the regulation of Mg(2+) homeostasis. Although there are indications
      that TRPM6 and TRPM7 can influence each other's cellular distribution and
      activity, little is known about the functional relationship between these two
      channel-kinases. In the present study, we examined how TRPM6 kinase activity
      influences TRPM7 serine phosphorylation, intracellular trafficking, and cell
      surface expression of TRPM7, as well as Mg(2+)-dependent cellular growth. We
      found TRPM7 serine phosphorylation via the TRPM6 kinase, but no TRPM6 serine
      phosphorylation via the TRPM7 kinase. Intracellular trafficking of TRPM7 was
      altered in HEK-293 epithelial kidney cells and DT40 B cells in the presence of
      TRPM6 with intact kinase activity, independently of the availability of
      extracellular Mg(2+), but TRPM6/7 surface labeling experiments indicate
      comparable levels of the TRPM6/7 channels at the plasma membrane. Furthermore,
      using a complementation approach in TRPM7-deficient DT40 B-cells, we demonstrated
      that wild-type TRPM6 inhibited cell growth under hypomagnesic cell culture
      conditions in cells co-expressing TRPM6 and TRPM7; however, co-expression of a
      TRPM6 kinase dead mutant had no effect-a similar phenotype was also observed in
      TRPM6/7 co-expressing HEK-293 cells. Our results provide first clues about how
      heteromer formation between TRPM6 and TRPM7 influences the biological activity of
      these ion channels. We show that TRPM6 regulates TRPM7 intracellular trafficking
      and TRPM7-dependent cell growth. All these effects are dependent upon the
      presence of an active TRPM6 kinase domain. Dysregulated Mg(2+)-homeostasis causes
      or exacerbates many pathologies. As TRPM6 and TRPM7 are expressed simultaneously
      in numerous cell types, understanding how their relationship impacts regulation
      of Mg(2+)-uptake is thus important knowledge.

PMID- 24858418
TI  - Targeted therapy for gastric cancer: molecular pathways and ongoing
      investigations.
AB  - Gastric cancer is currently the second leading cause of worldwide cancer
      mortality. Ongoing collaborative sequencing efforts have highlighted recurrent
      somatic genomic aberrations in gastric cancer, however, despite advances in
      characterizing the genomic landscape, there have been few advances in patient
      outcomes. Prognosis remains poor with a median overall survival of 12 months for
      advanced disease. The improved survival with trastuzumab, and more recently
      ramucirumab, underscore the promise of targeted and biologic therapies and the
      importance of molecular tumor characterization in gastric cancer. Here we review
      the most frequent actionable alterations in gastric cancer and highlight ongoing
      clinical investigations attempting to translate biologic understanding into
      improved clinical outcomes.

PMID- 24858419
TI  - Extracellular matrix protein laminin induces matrix metalloproteinase-9 in human
      breast cancer cell line mcf-7.
AB  - Studies on interaction of tumor cells with extracellular matrix (ECM) components
      showed increased extracellular protease activity mediated by the family of matrix
      metalloproteinases (MMPs). Here we studied the effect of human breast cancer cell
      line MCF-7-laminin (LM) interaction on MMPs and the underlying signaling
      pathways. Culturing of MCF-7 cells on LM coated surface upregulated MMP-9
      expression as well as reduced tissue inhibitor of metalloproteinases-1 (TIMP-1)
      expression. LM induced MMP-9 expression is abrogated by the blockade of alpha2
      integrin. Inhibitor studies indicate possible involvement of phosphatidyl
      inositol-3-kinase (PI3K), extracellular signal regulated kinase (ERK) and nuclear
      factor-kappaB (NF-kappaB) in LM induced signaling. LM treatment also enhanced
      phosphorylation of FAK (focal adhesion kinase), PI3K, ERK; nuclear translocation
      of ERK, pERK, NF-kappaB and cell migration. Our findings indicate that, binding
      of MCF-7 cells to LM, possibly via alpha2beta1 integrin, induces signaling
      involving FAK, PI3K, ERK, NF-kappaB followed by upregulation of MMP-9 and cell
      migration. 

PMID- 24858420
TI  - The more you ignore me the closer I get: An ERP study of evaluative priming.
AB  - We used event-related brain potentials (ERPs) to investigate the various mental
      processes contributing to evaluative priming-that is, more positive judgments for
      targets preceded by affectively positive, as opposed to negative, prime stimuli.
      To ensure ecological validity, we employed a priori meaningful landscape pictures
      as targets and emotional adjectives as visual primes and presented both primes
      and targets for relatively long durations (>1 s). Prime-related lateralized
      readiness potentials (LRPs) revealed response priming as one source of the
      significant evaluative priming effect. On the other hand, greater right-frontal
      positive slow wave in the ERP for pictures following negative, as compared with
      positive, primes indicated altered impression formation, thus supporting
      automatic spreading activation and/or affect misattribution accounts. Moreover,
      target LRPs suggested conscious counter-control to reduce the evaluative priming
      net effect. Finally, when comparing prime ERPs for two groups of participants
      showing strong versus weak evaluative priming, we found strong evidence for the
      role of depth of prime processing: In the weak-effect group, prime words evoked
      an increased visual P1/N1 complex, a larger posterior P2 component, and a greater
      left-parietal processing negativity presumably reflecting semantic processing. By
      contrast, a larger medial-frontal P2/N2 complex in the strong-effect group
      suggested top-down inhibition of the prime's emotional content. Thus, trying to
      ignore the primes can actually increase, rather than decrease, the evaluative
      priming effect.

PMID- 24858417
TI  - Quality control of homologous recombination.
AB  - Exogenous and endogenous genotoxic agents, such as ionizing radiation and
      numerous chemical agents, cause DNA double-strand breaks (DSBs), which are highly
      toxic and lead to genomic instability or tumorigenesis if not repaired accurately
      and efficiently. Cells have over evolutionary time developed certain repair
      mechanisms in response to DSBs to maintain genomic integrity. Major DSB repair
      mechanisms include non-homologous end joining and homologous recombination (HR).
      Using sister homologues as templates, HR is a high-fidelity repair pathway that
      can rejoin DSBs without introducing mutations. However, HR execution without
      appropriate guarding may lead to more severe gross genome rearrangements. Here we
      review current knowledge regarding the factors and mechanisms required for
      accomplishment of accurate HR. 

PMID- 24858421
TI  - A comprehensive phylogenetic and structural analysis of the carcinoembryonic
      antigen (CEA) gene family.
AB  - The carcinoembryonic antigen (CEA) gene family belongs to the immunoglobulin (Ig)
      superfamily and codes for a vast number of glycoproteins that differ greatly both
      in amino acid composition and function. The CEA family is divided into two
      groups, the carcinoembryonic antigen-related cell adhesion molecules (CEACAMs)
      and the pregnancy-specific glycoproteins. The CEA family members are implicated
      in pleiotropic (patho)physiological functions including cell-cell adhesion,
      pregnancy, immunity, neovascularization, regulation of insulin homeostasis, and
      carcinogenesis. In general, the CEA-encoded proteins are composed of an
      extracellular region with Ig variable and constant-like domains and a cytoplasmic
      region containing signaling motifs. Of particular interest, the well-studied
      human and mouse CEA genes are arranged in clusters in a single chromosome. Taking
      into account this characteristic, we made an effort to reconstruct the
      evolutionary history of the CEA gene family. Toward this end, the publicly
      available genomes were searched extensively for CEA homologs. The domain
      organization of the retrieved protein sequences was analyzed, and, subsequently,
      comprehensive phylogenetic analyses of the entire length CEA homologous proteins
      were performed. A series of evolutionarily conserved amino acid residues,
      functionally important, were identified. The relative positioning of these
      residues on the modeled tertiary structure of novel CEA protein domains revealed
      that they are, also, spatially conserved. Furthermore, the chromosomal
      arrangement of CEA genes was examined, and it was found that the CEA genes are
      preserved in terms of position, transcriptional orientation, and number in all
      species under investigation. 

PMID- 24858422
TI  - rIL-22 as an adjuvant enhances the immunogenicity of rGroEL in mice and its
      protective efficacy against S. Typhi and S. Typhimurium.
AB  - Salmonella infection, ranging from mild, self-limiting diarrhea to severe
      gastrointestinal, septicemic disease and enteric fever, is a global health
      problem both in humans and animals. Rapid development of microbial drug
      resistance has led to a need for efficacious and affordable vaccines against
      Salmonella. Microbial heat shock proteins (HSPs), including HSP60 and HSP70, are
      the dominant antigens that promote the host immune response. Co-administration of
      these antigens with cytokines, such as IL-22, which plays an important role in
      antimicrobial defense, can enhance the immune response and protection against
      pathogens. Therefore, the aim of the present study was to determine the
      immunogenicity of rGroEL (Hsp60) of S. Typhi, alone or administered in
      combination with murine rIL-22, and its protective efficacy against lethal
      infection with Salmonella, in mice. There was appreciable stimulation of the
      humoral and cell-mediated immune responses in mice immunized with rGroEL alone.
      However, co-administration of rGroEL with rIL-22 further boosted the antibody
      titers (IgG, IgG1 and IgG2a), T-cell proliferative responses and the secretion of
      both Th1 and Th2 cytokines. Additionally, rGroEL alone accorded 65%-70%
      protection against lethal challenge with S. Typhi and S. Typhimurium, which
      increased to 90% when co-administered with rIL-22. 

PMID- 24858423
TI  - Impact of renal denervation on 24-hour ambulatory blood pressure: results from
      SYMPLICITY HTN-3.
AB  - BACKGROUND: Prior studies of catheter-based renal artery denervation have not
      systematically performed ambulatory blood pressure monitoring (ABPM) to assess
      the efficacy of the procedure. OBJECTIVES: SYMPLICITY HTN-3 (Renal Denervation in
      Patients With Uncontrolled Hypertension) was a prospective, blinded, randomized,
      sham-controlled trial. The current analysis details the effect of renal
      denervation or a sham procedure on ABPM measurements 6 months post-randomization.
      METHODS: Patients with resistant hypertension were randomized 2:1 to renal
      denervation or sham control. Patients were on a stable antihypertensive regimen
      including maximally tolerated doses of at least 3 drugs including a diuretic
      before randomization. The powered secondary efficacy endpoint was a change in
      mean 24-h ambulatory systolic blood pressure (SBP). Nondipper to dipper
      (nighttime blood pressure [BP] 10% to 20% lower than daytime BP) conversion was
      calculated at 6 months. RESULTS: The 24-h ambulatory SBP changed -6.8 +/- 15.1 mm
      Hg in the denervation group and -4.8 +/- 17.3 mm Hg in the sham group: difference
      of -2.0 mm Hg (95% confidence interval [CI]: -5.0 to 1.1; p = 0.98 with a 2 mm Hg
      superiority margin). The daytime ambulatory SBP change difference between groups
      was -1.1 (95% CI: -4.3 to 2.2; p = 0.52). The nocturnal ambulatory SBP change
      difference between groups was -3.3 (95 CI: -6.7 to 0.1; p = 0.06). The percent of
      nondippers converted to dippers was 21.2% in the denervation group and 15.0% in
      the sham group (95% CI: -3.8% to 16.2%; p = 0.30). Change in 24-h heart rate was 
      1.4 +/- 7.4 in the denervation group and -1.3 +/- 7.3 in the sham group; (95% CI:
      -1.5 to 1.4; p = 0.94). CONCLUSIONS: This trial did not demonstrate a benefit of
      renal artery denervation on reduction in ambulatory BP in either the 24-h or day
      and night periods compared with sham (Renal Denervation in Patients With
      Uncontrolled Hypertension [SYMPLICITY HTN-3]; NCT01418261).

PMID- 24858425
TI  - Radiolabeled anti-CD45 antibody with reduced-intensity conditioning and
      allogeneic transplantation for younger patients with advanced acute myeloid
      leukemia or myelodysplastic syndrome.
AB  - We treated patients under age 50 years with iodine-131 ((131)I)-anti-CD45
      antibody combined with fludarabine and 2 Gy total body irradiation to create an
      improved hematopoietic cell transplantation (HCT) strategy for advanced acute
      myeloid leukemia or high-risk myelodysplastic syndrome patients. Fifteen patients
      received 332 to 1561 mCi of (131)I, delivering an average of 27 Gy to bone
      marrow, 84 Gy to spleen, and 21 Gy to liver. Although a maximum dose of 28 Gy was
      delivered to the liver, no dose-limiting toxicity was observed. Marrow doses were
      arbitrarily capped at 43 Gy to avoid radiation-induced stromal damage; however,
      no graft failure or evidence of stromal damage was observed. Twelve patients
      (80%) developed grade II graft-versus-host disease (GVHD), 1 patient developed
      grade III GVHD, and no patients developed grade IV GVHD during the first 100 days
      after HCT. Of the 12 patients with chronic GVHD data, 10 developed chronic GVHD,
      generally involving the skin and mouth. Six patients (40%) are surviving after a
      median of 5.0 years (range, 4.2 to 8.3 years). The estimated survival at 1 year
      was 73% among the 15 treated patients. Eight patients relapsed, 7 of whom
      subsequently died. The median time to relapse among these 8 patients was 54 days
      (range, 26 to 1364 days). No cases of nonrelapse mortality were observed in the
      first year after transplantation. However, 2 patients died in remission from
      complications of chronic GVHD and cardiomyopathy, at 18 months and 14 months
      after transplantation, respectively. This study suggests that patients may
      tolerate myeloablative doses >28 Gy delivered to the liver using (131)I-anti-CD45
      antibody in addition to standard reduced-intensity conditioning. Moreover, the
      arbitrary limit of 43 Gy to the marrow may be unnecessarily conservative, and
      continued escalation of targeted radioimmunotherapy doses may be feasible to
      further reduce relapse. 

PMID- 24858427
TI  - [Effects of implementation of psychiatric out-patient clinics
      ("institutsambulanzen") on hospital admissions].
AB  - OBJECTIVE: In the German federal state Baden-Wuerttemberg psychiatric out-patient
      clinics ("Institutsambulanzen") have been implemented since 2002, later than
      elsewhere. The effects of these new out-patient services on the use of in-patient
      services should be examined in a defined catchment area. METHOD: Data on the use
      of in-patient services 2002 - 2011 was recorded from psychiatric hospitals and
      day hospitals in a catchment area of 862 000 inhabitants as well as data from the
      corresponding out-patient clinics. RESULTS: While the number of patients in the
      out-patient clinics increased from 1986 in 2002 to 7925 in 2011, the number of
      hospitalised patients increased only moderately, from 4452 in 2002 to 4930 in
      2011. An increasing percentage of patients in the out-patients clinic did not use
      in-patient services in the respective year. This concerned particularly patients
      with adjustment and personality disorders, who do not find other appropriate
      psychotherapeutic care as out-patients. CONCLUSIONS: The implementation of out
      patient clinics had no significant effect on the number of hospitalisations and
      occupied beds.

PMID- 24858426
TI  - How subtle is the "terroir" effect? Chemistry-related signatures of two "climats
      de Bourgogne".
AB  - The chemical composition of grape berries is influenced by various environmental
      conditions often considered to be representative of a "terroir". If grapes from a
      given terroir are assumed to reflect this origin in their chemical compositions,
      the corresponding wine should also reflect it. The aim of this work was therefore
      to reveal the "terroir" expression within the chemodiversity of grapes and
      related wines, using ultrahigh-resolution mass spectrometry. Grapes and
      corresponding wines, from two distinct - though very proximate - terroirs of
      Burgundy were analyzed over three vintages (2010, 2011 and 2012). Ultrahigh
      resolution mass spectrometry and ultra-high performance liquid chromatography
      were used as untargeted and targeted approaches to discriminate complex chemical
      fingerprints for vintages, classes (wines, skins or musts), and terroirs.
      Statistical analyses revealed that even if vintages have the most significant
      impact on fingerprints, the most significant terroir differences are seen in the
      grapes of a given vintage. 

PMID- 24858428
TI  - [Impact of the Temporaneous Lack of Legal Basis for Involuntary Treatment on the
      Frequency of Aggressive Incidents, Seclusion and Restraint among Patients with
      Chronic Schizophrenic Disorders].
AB  - OBJECTIVE: In the German federal state Baden-Wuerttemberg involuntary medication
      of detained psychiatric inpatients was unlawful during eight months from July
      2012 until February 2013 due to a decision of the Federal Constitutional Court
      except for emergency situations. We examined whether aggressive incidents and
      mechanical coercive measures such as seclusion and restraint increased. METHODS:
      Routine data of 2.644 cases with schizophrenic and manic disorders in seven
      psychiatric hospitals were analysed by a pooled cross-section analysis as well as
      by a longitudinal analysis for the relevant time period and the corresponding
      period of the preceding year. RESULTS: The number of mechanical coercive measures
      and of aggressive incidents increased significantly by over 40 % in the cross
      sectional analysis. In the longitudinal analysis which included only patients
      with admissions in both periods, the increase of both aggressive incidents and
      coercive measures was over 100 %. Effects on the duration of measures were
      insignificant. CONCLUSION: The temporaneous impossibility to apply involuntary
      medication was associated with a significant increase of aggressive incidents,
      seclusion, and mechanical restraint.

PMID- 24858429
TI  - [Burden of mothers and fathers of persons with schizophrenia].
AB  - OBJECTIVE: Most studies about the burden of schizophrenia carers included only
      one care-giving relative, usually the patients' mothers. The present study
      intended to analyse differences of the level of burden between mothers and
      fathers of the same patients. METHODS: 101 mothers and 101 fathers of the same
      patients suffering from schizophrenia were included into this study. They were
      assessed by means of the "Involvement Evaluation Questionnaire" and the "Carers'
      Needs Assessment for Schizophrenia". RESULTS: Mothers showed significantly higher
      scores than fathers regarding the subscores "Tensions" and "Urging". Multiple
      linear regression analyses showed positive associations between the frequency of
      mothers' as well as fathers' unmet needs and dimensions of caregiver involvement.
      CONCLUSION: Unmet needs among mothers and fathers have negative effects on their
      burden. The differences between mothers and fathers indicate the importance of
      considering the carer's gender in clinical work.

PMID- 24858431
TI  - [Predicting the Number of Office-Based Psychiatrists Needed in the Future:
      Potential and Limitations].
AB  - OBJECTIVE: This study discusses the potential and the limitations of medical
      workforce planning in outpatient psychiatry in Switzerland. METHODS: Hypotheses
      concerning selected factors influencing the number of office-based psychiatrists
      needed in the future were formulated. In a next step, those hypotheses were
      assigned to one of three scenarios (high, constant, and normal need development).
      On the basis of these three scenarios, the number of psychiatrists needed was
      calculated. RESULTS: Taken together, the results from the scenarios indicate an
      undersupply of office-based psychiatrists for the next 20 years. CONCLUSION:
      Estimating the number office-based psychiatrists needed in the future is
      basically feasible and reasonable. But according to the actual state of
      knowledge, only crude estimations are possible. There is a need for more research
      in this area.

PMID- 24858430
TI  - [The Quality of Inpatient Treatment of Elderly with Major Depression].
AB  - OBJECTIVE: There are highly effective treatments either in inpatient or day
      hospital settings available for elderly with major depression. It is important to
      consider some specific needs of elderly people (e. g. higher somatic
      comorbidities). METHODS: On the base of a large routine data set (139 307
      patients in hospital treatment) differences between elderly and younger people
      with major depression are investigated. RESULTS: Elderly with major depression
      receive significantly less day hospital treatment and psychotherapy.
      Surprisingly, the mean length of hospital stay was significantly longer in
      younger patients with major depression. CONCLUSION: The results from such routine
      data should be interpreted with caution. Never the less our results suggest that
      there is still room for improvement for elderly people with major depression.

PMID- 24858432
TI  - [Comorbidity of diabetes mellitus and depression in the general population in
      Germany].
AB  - OBJECTIVE: To assess the comorbidity of diabetes and depression in the adult
      general population of Germany. METHODS: Data (n = 43 312) derived from the
      representative cross-sectional telephone survey "German Health Update (GEDA)".
      Information about diagnosed chronic somatic diseases including diabetes and
      diagnosed depression was available for residents in private households. Age- and
      sex-specific adjusted logistic regressions were used to examine the association
      between diabetes and depression. RESULTS: 12-month prevalences: diagnosed
      diabetes 7.4 %, diagnosed depression 6.7 %, comorbidity of both 0.8 %. An
      association of diabetes and depression was found in people < 50 years and in
      women aged 50 - 64 years. This association was dependent on the number of
      additional chronic diseases. CONCLUSION: Comorbidity of diabetes and depression
      was quite rare. Yet according to our results every 10(th) adult with diagnosed
      diabetes gets a depression diagnosis and every 9(th) adult with diagnosed
      depression has known diabetes. Underestimation for men and older adults due to
      diagnostic bias is possible. The combination of diabetes and depression is
      relevant for medical care because of its health burden.

PMID- 24858433
TI  - [Does low resilience causes to greater psychological impairment?].
AB  - AIM: The purpose of this article is an analysis of the association between
      resilience, age and gender with psychological distress through anxiety and
      depression. METHODS: In a sample of 3784 individuals, the association of
      resilience with anxiety and depression was examined using a linear regression
      model. In addition to resilience, age and gender as well as the combination of
      these factors and their effects on resilience were analyzed. RESULTS: Low
      resilience predicts both anxiety and depression. Gender moderates this
      association. In male persons a stronger association between resilience and
      depression was found. CONCLUSION: In practice, these results should be considered
      in treatment.

PMID- 24858434
TI  - [Mental Health Care Utilization of First Generation Vietnamese Migrants in
      Germany].
AB  - OBJECTIVE: Vietnamese migrants underutilize and are a "hard to reach group"
      within the existing mental health care system in Germany. METHODS: We analyzed
      migration related and clinical data for all first-time Vietnamese migrants
      seeking psychiatric help, within the first 30 months of a newly established
      outpatient clinic, offering culture-sensitive psychiatric treatment in native
      Vietnamese language. RESULTS: Most first time patients were female, first
      generation Vietnamese migrants with poor German language skills. Only 1 /3 of all
      patients had a psychiatric history, while this number was higher in patients with
      schizophrenia. Over time, more first time patients with depression were seeking
      psychiatric care, accompanied with an increase of non-professional referrals
      within the Vietnamese communities. CONCLUSION: This first study on mental health
      care utilization in Vietnamese migrants in Germany points towards the fact that
      "migrants" cannot be considered as a homogeneous group. Mental health care
      utilization must be evaluated for specific migrant groups, and can be initially
      improved if offered in native language and when it is referred to by members of
      migrant communities.

PMID- 24858435
TI  - [Stepwise outpatient care].
AB  - OBJECTIVE: To assess possible differences in clinical, social, care, and
      satisfaction profile of patients treated by outpatient clinics or office based
      psychiatrists. METHOD: The study sample consists of 100 patients of a psychiatric
      outpatient clinic and 100 patients treated by office based psychiatrists in the
      same catchment area. Patients were examined using standardized assessment
      instruments for severity of illness (HoNOS, CGI), general (GAF) and specific
      functional impairment (PSP), and satisfaction with psychiatric services (ZUF-8).
      Chi-square tests, univariate ANOVAs and stepwise multivariate logistic regression
      models were applied. RESULTS: Compared with patients treated by office based
      psychiatrists, patients treated by the outpatient clinic showed higher HoNOS and
      CGI scores, lower GAF and PSP scores, and had more often a disability pension, a
      legal guardianship, a schizophrenia diagnosis, suicide attempts,
      hospitalizations, and therapeutic contacts. However, there were no significant
      differences regarding care satisfaction. CONCLUSION: The assessed outpatient
      clinic met the German statutory criteria for its legitimation. However, care
      needs have to be specified in a better way, and the different care intensity as
      well as concrete interventions between both settings have to be specified more
      accurately.

PMID- 24858436
TI  - [Karl Jaspers and the challenges of social psychiatry].
AB  - Karl Jaspers, in his book "General Psychopathology", argued for methodological
      pluralism rather than theoretical dogmatism. He formulated a methodological order
      of psychopathology with a distinction between "explanation" (objective
      psychopathology) and "understanding" (subjective psychopathology, psychopathology
      of meaning). The latter approach focused on patients' subjective experience and
      biographical issues. Karl Jaspers emphasised social factors in the genesis and
      course of mental disorders. Following a multiperspective concept, from Jaspers'
      viewpoint social psychiatry should consider itself of equal importance with
      biological and psychotherapeutic psychiatry. Therefore, uncritical generalization
      of one of these perspectives should be avoided. Personalized psychiatry, apart
      from searching biological markers to tailor treatment should identify
      psychosocial factors and subjective meaning. Concepts of recovery should not
      ignore biological foundations in mental disorders. 

PMID- 24858437
TI  - Nasopharyngeal tonsils (adenoids) contain extrathymic corticothymocytes.
AB  - Adenoidal tissue (also known as nasopharyngeal tonsils) of 58% of humans in the
      pediatric age group contains immature T-lymphoid cells with the phenotype of
      thymocytes (TdT+, CD1abc+, cytoplasmic CD3+, coexpressing CD4 and CD8, lacking an
      Intraepithelial Lymphocyte-associated phenotype). The notable difference in
      comparison to palatine tonsils is the clustering in groups and sheets, comprising
      hundreds or thousands of cells (1.7%+/-0.2 of total T cells). The thymic
      epithelium is morphologically and phenotypically absent. Adenoids share with
      tonsils and lymph nodes the presence of immature B cell precursors (TdT+, CD1a-,
      Pax5+, Surrogate light chain+/-), however in these latter the presence of TdT+,
      CD1a+, Pax5- precursors is absent or limited to individual cells. Human adenoids
      are distinct among the Waldeyer's ring lymphoid tissue because of the known
      embryogenic derivation from the third pharyngeal pouch, from which the thymus
      develops; in addition, they may display phenotypic incomplete features of a
      vestigial thymus.

PMID- 24858439
TI  - Adolescents of parents with chronic pain whose parents were 'shut off' report
      more hardship and feelings of distance than those with a more open relationship.

PMID- 24858440
TI  - Exposure to selective serotonin reuptake inhibitors in late pregnancy increases
      the risk of persistent pulmonary hypertension of the newborn, but the absolute
      risk is low.

PMID- 24858441
TI  - A bottle-weaning counselling intervention for parents of 12-month-old infants
      reduces bottle use at age 24 months but has no effect on child weight.

PMID- 24858442
TI  - Evidence relating to the effectiveness of community-based interventions to
      improve the quality of life for children of parents with serious mental illness
      is weak; better quality studies are required.

PMID- 24858443
TI  - Patient participation in surgical treatment decision-making can be measured using
      a 16-item scale with four distinct dimensions.

PMID- 24858444
TI  - Obligatory averaging in mean size perception.
AB  - The perception of ensemble characteristics is often regarded as an antidote to an
      established bottleneck in focused attention and working memory, both of which
      appear to be limited in capacity to a few objects only. In order to test the
      associative law of summation, observers were asked to estimate the mean size of
      four circles relative to a reference circle. When there was no time to scrutinize
      each individual circle, observers discriminated the mean size difference
      identically, irrespective of whether the same summary size increment or decrement
      was added to or subtracted from the size of only one, two, or all four circles.
      Since observers judged the size of individual circles, the position of which was
      indicated after they were displayed, considerably less accurately than the mean
      size of the four circles, it is very unlikely that explicit knowledge of the size
      of the individual elements is the basis of mean size judgments. The sizes of
      individual elements were pooled together in an obligatory manner before size
      information had reached awareness. The processing of size information seems to be
      largely constrained to only one measure at a time, with a preference for mean
      size rather than the individual measures from which it is assembled. 

PMID- 24858445
TI  - Novel investigational approaches for inhibiting angiogenesis in recurrent
      glioblastoma.

PMID- 24858446
TI  - Development of planning in 4- to 10-year-old children: reducing inhibitory
      demands does not improve performance.
AB  - Currently, there are relatively few tasks suitable for testing planned problem
      solving in children. We presented 4- to 10-year-old children (N=172) with two
      planning tasks (sequential planning and advance planning) using the paddle-box
      apparatus, which was originally designed to investigate the planning skills of
      nonhuman apes. First, we were interested in the development of children's
      performance in the two tasks and whether the strategies children used to succeed
      differed among age groups. Performance improved significantly across age groups
      in both tasks. Strategies for success in the advance planning task differed among
      age groups, with 4- and 5-year-olds performing more excess actions, and a greater
      proportion of irrelevant excess actions, than older children. Findings are
      discussed in relation to the development of performance in tower tasks, which are
      a commonly used test of planning ability in humans. Second, based on previous
      findings with apes, we predicted that introducing measures to reduce the
      inhibitory demands of the advance planning task would improve children's
      performance. Therefore, in this study we introduced two methodological
      alterations that have been shown to improve children's performance in other tasks
      with inhibitory demands: (a) imposing a short delay before a child is allowed to
      act and (b) replacing reward items with symbolic tokens. Surprisingly, neither of
      these measures improved the performance of children in any of the age groups,
      suggesting that, contrary to our prediction, inhibitory control might not be a
      key performance-limiting factor in the advance planning paddle-box task. 

PMID- 24858448
TI  - Numerical spatio-temporal characterization of Listeria monocytogenes biofilms.
AB  - As the structure of biofilms plays a key role in their resistance and
      persistence, this work presents for the first time the numerical characterization
      of the temporal evolution of biofilm structures formed by three Listeria
      monocytogenes strains on two types of stainless-steel supports, AISI 304 SS No.
      2B and AISI 316 SS No. 2R. Counting methods, motility tests, fluorescence
      microscopy and image analysis were combined to study the dynamic evolution of
      biofilm formation and structure. Image analysis was performed with several well
      known parameters as well as a newly defined parameter to quantify spatio-temporal
      distribution. The results confirm the interstrain variability of L. monocytogenes
      species regarding biofilm structure and structure evolution. Two types of biofilm
      were observed: homogeneous or flat and heterogeneous or clustered. Differences in
      clusters and in attachment and detachment processes were due mainly to the
      topography and composition of the two surfaces although an effect due to motility
      was also found. 

PMID- 24858447
TI  - Task difficulty and life changes among stroke family caregivers: relationship to
      depressive symptoms.
AB  - OBJECTIVES: To investigate differences in stroke caregiver task difficulty and
      life changes based on level of caregiver depressive symptoms, and to estimate
      probabilities among task difficulty and life change items. DESIGN: Descriptive
      analysis of baseline data from an ongoing stroke caregiver intervention trial.
      SETTING: Hospitals and rehabilitation facilities. PARTICIPANTS: Caregivers
      (N=242; 78.6% women; 47.7% spouses; 71.8% white; mean age, 54.2+/-12.1y) caring
      for stroke survivors within 8 weeks of discharge to home. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: Baseline measures for task difficulty (Oberst
      Caregiving Burden Scale) and life changes (Bakas Caregiving Outcomes Scale) were
      compared based on level of depressive symptoms (Patient Health Questionnaire-9
      [PHQ-9] scores <5 means no depressive symptoms; n=126; PHQ-9 scores >=5 means
      mild to severe depressive symptoms, n=116). Mean scores were analyzed using
      general linear modeling, with item analyses using logistic regression and the
      Benjamini-Hochberg method to control type I error inflation. RESULTS: Caregivers
      with mild to severe depressive symptoms have greater difficulty with tasks and
      worse life changes than those with no depressive symptoms (P<.001). Odds ratios
      were highest for the task of arranging care while away and for negative life
      changes (eg, addressing self-esteem, coping with stress, physical health).
      CONCLUSIONS: Findings underscore the importance of depressive symptom screening
      for stroke caregivers during or shortly after discharge. Assisting caregivers
      with depressive symptoms to arrange for respite care and addressing negative
      physical and psychological changes may be priority areas for future
      interventions.

PMID- 24858449
TI  - Clinical evaluation of a disposable amperometric magneto-genosensor for the
      detection and identification of Streptococcus pneumoniae.
AB  - A disposable PCR-based amperometric magneto-genosensor for detection and
      identification of Streptococcus pneumoniae was evaluated. ROC curve analysis used
      to determine optimal signal cutoff values yielded a sensitivity of 91% and a
      specificity of 90%. The method was also tested for the direct detection of
      pneumococci in clinical samples. 

PMID- 24858450
TI  - Taxonomic database and cut-off value for processing mcrA gene 454 pyrosequencing
      data by MOTHUR.
AB  - The functional mcrA gene of methanogens can generate phylogeny as congruent as
      the 16S rRNA gene phylogeny. For the mcrA sequences amplified by mlas/mcrA-rev
      primers, we created a database for taxonomical classification and propose cut-off
      values for OTU clustering and further analysis of alpha- and beta-diversity with
      the MOTHUR software. 

PMID- 24858451
TI  - Artificial sweat composition to grow and sustain a mixed human axillary
      microbiome.
AB  - A novel artificial sweat composition, Skin Community Interaction simulation,
      designed to mimic the human axillary sweat, was compared to other artificial
      sweat compositions. Axillary microbiota grown in the novel composition closely
      resembled the original community. Volatile organic compound analysis showed good
      correlations with in vivo axillary (mal)odor components. 

PMID- 24858452
TI  - Carpal tunnel syndrome - anatomical and clinical correlations.
AB  - Carpal tunnel syndrome (CTS) is the most common and widely known of the
      entrapment neuropathies in which the body's peripheral nerves are compressed.
      Common symptoms of CTS involve the hand and result from compression of the median
      nerve within the carpal tunnel. In general, CTS develops when the tissues around
      the median nerve irritate or compress on the nerve along its course through the
      carpal tunnel, however often it is very difficult to determine cause of CTS.
      Proper treatment (conservative or surgical) usually can relieve the symptoms and
      restore normal use of the wrist and hand. 

PMID- 24858453
TI  - Efficacy of deep brain stimulation of the subthalamic nucleus on autonomic
      dysfunction in patients with Parkinson's disease.
AB  - Subthalamic nucleus (STN) deep brain stimulation (DBS) is well established for
      the treatment of the motor symptoms of Parkinson's disease (PD). However, the
      effect of STN DBS on autonomic symptoms has not been well studied. We examined 19
      patients undergoing STN DBS for PD. The patients were administered a
      questionnaire to evaluate the pre-operative and post-operative autonomic
      function. All patients reported a significant post DBS improvement of one or more
      symptoms of the autonomic dysfunction (urinary and gastrointestinal function). In
      particular, we have shown the most significant improvement in the urinary
      function after STN DBS. Further larger studies are required with respect to the
      effect of STN DBS on the autonomic function. 

PMID- 24858454
TI  - Green fiber lasers in urology.
AB  - We performed morphometric, scanning electron microscope and chemical studies of
      the working ends of KTP-green light laser fibers used in urology. The type and
      degree of damage depended on the amount of laser work. We proposed fiber
      recycling technology. 

PMID- 24858455
TI  - Empathy and burnout among physicians of different specialities.
AB  - AIM: The aim of this study was to assess the level of empathy and burnout among
      physicians of different specialization, as well as to determine whether a
      correlation existed between the level of empathy and burnout. MATERIALS AND
      METHOD: Seventy-one physicians took part in the study - 25 women (35.2%) and 46
      men (age between 25 to 68 years). The physicians were either employed in
      hospitals, outpatient clinics or university departments in Krakow. The
      participants were asked to fill out a personal questionnaire, the Maslach Burnout
      Inventory (MBI) and the Emotional Empathy Scale (EES) as well as describe four
      chosen tables from the Thematic Apperception Test (TAT). RESULTS: The average
      empathy score for the whole group was 14.3 (SD +/- 6.4). The average levels of
      each of the burnout (according to MBI) elements for the whole group were 21.72
      for emotional exhaustion, 9.62 for depersonalization and 29.07 for loss of
      personal accomplishment. For the whole group a negative correlation was noted
      between loss of personal accomplishment (according to MBI) and the level of
      empathy (according to EES) (r = -0.23, p <0.05). For the whole group negative
      correlations were noted between the level of emotional exhaustion,
      depersonalization and the total level of burnout (according to MBI) and the level
      of empathy (according to TAT) (r = -0.30, p <0.05; r = -0.39, p <0.01; p = -0.32,
      p <0.01 respectively). CONCLUSIONS: Concluding, medical specialists have a
      significantly higher level of empathy than surgeons and family physicians. It is
      imperative to remember that increasing depersonalization and emotional exhaustion
      can have a negative impact on empathy.

PMID- 24858456
TI  - The changes of heart rate variability in response to deep breathing in
      professional swimmers.
AB  - INTRODUCTION: The analysis of heart rate variability (HRV) is a useful tool for
      the evaluation of adaptation processes of autonomic nervous system (ANS) to
      physical exercise. The deep breathing test (DB) induces the increased activity of
      the parasympathetic component of ANS. The aim of the study was to evaluate the
      influence of DB on ANS activity in professional swimmers and non-trained persons.
      METHODS: The study included 10 healthy swimmers (5 women and 5 men, mean age 21
      +/- 2 yrs) in the transitory phase of their training cycle, and a control group
      comprising 31 healthy volunteers. The evaluation of ANS activity was based on the
      time and frequency domain indices of HRV determined at rest and during DB.
      RESULTS: Compared to the controls, swimmers were characterized by significantly
      higher values of the following HRV indices determined at rest: mRR (902.9 +/-
      102.5 ms vs. 744 +/- 67.5 ms, p <0.05), rMSSD (71.4 +/- 46.9 ms vs. 41.3 +/- 20.7
      ms, p <0.05), pNN50 (28.3 +/- 17.4% vs.14 +/- 10.7%, p <0.05), LF (603.5 +/-
      208.2 ms2 vs. 445.2 +/- 137 ms2, p <0.03). Also during DB test, the values of the
      following HRV indices of the swimmers were significantly higher than in the
      controls: mRR (899.2 +/- 69.2 ms vs. 766.4 +/- 63.6 ms, p <0.05), SDNN (114.1 +/-
      45.1 ms vs. 79 +/- 27.7 ms, p <0.05), rMSDD (81.9 +/- 38.2 ms vs. 50.7 +/- 27 ms,
      p <0.05), pNN50 (32.9 +/- 14.3 % vs. 20.6 +/- 14.6%, p <0.05), TP (1972.7 +/-
      809.5 ms2 vs. 1329.7 +/- 532 ms2, p <0.05), HF (657.1 +/- 330.9 ms2 vs. 405.7 +/-
      217 ms2, p <0.05), LF (753.3 +/- 294 ms2 vs. 533 +/- 213.4 ms2, p <0.05). The
      analysis of value relative DB-induced changes in time and frequency domain HRV
      indices revealed significant intergroup differences in reaction to
      parasympathetic stimulation. CONCLUSIONS: Based on the results presented in this
      study, the swimmers' response to deep breathing seems stronger than in persons
      without professional training. The deep breathing test may be a useful tool to
      evaluate the dynamic changes in the parasympathetic activity of ANS of
      sportspersons.

PMID- 24858457
TI  - Morphological features of the macerated cranial bones registered by the 3D vision
      system for potential use in forensic anthropology.
AB  - In this paper we present potential usage of the 3D vision system for registering
      features of the macerated cranial bones. Applied 3D vision system collects height
      profiles of the object surface and from that data builds a three-dimensional
      image of the surface. This method appeared to be accurate enough to capture
      anatomical details of the macerated bones. With the aid of the 3D vision system
      we generated images of the surface of the human calvaria which was used for
      testing the system. Performed reconstruction visualized the imprints of the dural
      vascular system, cranial sutures, and the three-layer structure of the cranial
      bones observed in the cross-section. We figure out that the 3D vision system may
      deliver data which can enhance estimation of sex from the osteological material. 

PMID- 24858458
TI  - The influence of curcumin on the action of etoposide in a rat acute myeloid
      leukemia cell line.
AB  - BACKGROUND: There are contradictory results from studies on the effect of
      curcumin, a plant phenolic compound with a well-established anticancer effect in
      vitro, on the action of etoposide in cancer cells. OBJECTIVE: The aim of this
      study was to evaluate the influence of curcumin on the genotoxic and cytostatic
      action of etoposide in the LT12 cell line derived from BN rat acute myeloid
      leukemia cells. MATERIAL & METHODS: The LT12 cells were treated with different
      doses of curcumin for 1-72 hours followed by application of etoposide. The amount
      of DNA damage was estimated via a comet assay. Viability, cell cycle and
      apoptosis were examined by using flow cytometry technique. RESULTS: The combined
      effect of curcumin and etoposide on viability was synergistic at low micro- molar
      concentrations. In comparison to treatment with curcumin and etoposide alone, co
      treatment with these compounds increased the extent of DNA damage, the percentage
      of cells arrested in the G2/M phase and the number of annexin-V-positive cells.
      CONCLUSIONS: The interaction between etoposide and curcumin points to an enhanced
      antileukemic potential to be derived from the combination of these compounds.

PMID- 24858459
TI  - Clinico-pathological predictive factors in squamous cell carcinoma of the tongue
      and the floor of the mouth.
AB  - INTRODUCTION: The incidence of oral squamous cell carcinoma (OSCC) comprises
      about 2% of all malignant neoplasms. Despite improvement in treatment modalities
      in OSCC the prognosis remains poor. AIM: The aim of this study is to evaluate
      clinical and histological predictive factors determining the risk of loco
      regional recurrence (LRR) and survival of the patients surgically treated for SCC
      of the tongue and the floor of the mouth (FOM). MATERIALS & METHODS: The study
      group consisted of 60 patients with primary SCC of the tongue and FOM who
      underwent surgical treatment without prior therapy. Clinical and histological
      factors, such as: age, sex of the patients, comorbidities, tumour site, stage,
      grade, lymph nodes and mandible involvement, margin status, type of neck
      dissection and adjuvant radiation therapy, influencing LRR and 5-year disease
      specific survival (DSS) were analysed. RESULTS: LRR was observed in 26 (43.3%)
      patients after 9.6 months on average (SD +/- 9.47) and DSS reached 53.3% (95%CI:
      40.0-66.3). LRR was more frequent in patients with SCC of the base of the tongue
      (p = 0.024), posterior part of FOM (p = 0.010) and who underwent MRND (p =
      0.043). Adverse impact on DSS had advanced stage of the disease (p = 0.048) and
      tongue cancer (p = 0.045). In multivariate Cox regression analysis SCC of the
      tongue achieved the status of independent predictor of LRR (p = 0.028) and DSS (p
      = 0.011). Lymph node involvement was the second independent predictor of LRR (p =
      0.008) as well as DSS (p = 0.015). CONCLUSIONS: The analysis of prognostic
      factors in SCC of tongue and FOM revealed that lymph node involvement was an
      independent predictor of LRR and DSS. Moreover, higher risk of LRR and death was
      observed in patients with tongue cancer, especially localised posteriorly.

PMID- 24858460
TI  - The level of perceived stress of parents of children with cancerous disease -
      mechanisms of dealing with stress and social support.
AB  - INTRODUCTION: Cancerous disorders are the second most common cause of death among
      children. Blood cancer is a stressful and traumatic situation for the child, as
      well as the parents. To overcome the stress of child's illness parents adopt
      different coping styles. In overcoming these difficulties, the invaluable role is
      played by social support they receive from medical staff, family or institution.
      AIM: To assess the feeling of stress for parents of children diagnosed with blood
      cancer, to determine how they choose to deal with stress in a difficult
      situation. MATERIAL AND METHODS: The study group consisted of 63 parents of
      children diagnosed with blood cancer. The study used the PSS-10 scale to assess
      the stress experienced by parents, 40 GP ISEL scale to assess social support,
      Inventory Ways to Measure Coping and the author's questionnaire. RESULTS: High
      perception of stress was observed among parents. It was found that the strategy
      based on active coping (taking action to improve the situation) got the highest
      scores among the strategies for coping with stress. The study showed that parents
      can most often count on material support. CONCLUSIONS: The feeling of stress
      severity among parents is high, particularly among women and people with higher
      education. The actions of medical team should take into account the needs of
      parents in raising and maintaining the resources to adapt to the difficult
      situation of child's disease.

PMID- 24858461
TI  - Blood vessels of the intratumoral septa in uterine leiomyomata.
AB  - The angioarchitecture of fibroid intratumoral septa was studied using 32 uteri
      obtained during necropsies of the females aged between 35-57. The whole vascular
      bed of 16 uteri was injected with synthetic resin Mercox CL-2R and then the uteri
      were corroded in potassium hydroxide. Next 16 uteri were injected with acrylic
      emulsion, Liquitex R. Their vascular bed was studied using immunohistochemistry
      for von Willebrandt's factor. Immunohistochemistry allowed to visualize the
      vessels within the intratumoral septa, while SEM allowed to differentiate the
      vessels, which were mainly the venules and the veins. Apart from the veins the
      intratumoral septa were consisted of small arteries and capillaries. 

PMID- 24858463
TI  - Virologic testing in bronchiolitis: does it change management decisions and
      predict outcomes?
AB  - The aim of this study was to evaluate the clinical, therapeutic, laboratory, and
      radiological differences between respiratory syncytial virus (RSV) and non-RSV
      bronchiolitis in order to assess if the prior knowledge of viral etiology changed
      management decisions and would be able to predict outcomes. Medical charts of
      children <1 year admitted to the emergency department with bronchiolitis during
      two RSV seasons (2010-2012) were reviewed. We analyzed 221 episodes of
      bronchiolitis. The percentage of exams performed (95 % confidence interval (CI)
      0.74-2.52), abnormal laboratory and radiological findings (95 % CI 0.53-16.89)
      did not differ between groups. RSV bronchiolitis had a more severe clinical
      course. However, virologic testing for RSV had low specificity in identifying at
      risk patients for hospitalization, longer hospital length of stay, and need of
      oxygen therapy and nasogastric tube (44, 40, 42, and 35 %, respectively), and
      while statistically significant, the positive likelihood ratios were only
      slightly greater than 1. CONCLUSION: Although RSV bronchiolitis has a more severe
      clinical course, virologic testing does not help in management decisions, and at
      an individual level, as a performance test, it seems insufficient to precisely
      predict outcomes.

PMID- 24858464
TI  - The ovary structure and oogenesis in the basal crustaceans and hexapods. Possible
      phylogenetic significance.
AB  - Recent large-scale phylogenetic analyses of exclusively molecular or combined
      molecular and morphological characters support a close relationship between
      Crustacea and Hexapoda. The growing consensus on this phylogenetic link is
      reflected in uniting both taxa under the name Pancrustacea or Tetraconata.
      Several recent molecular phylogenies have also indicated that the monophyletic
      hexapods should be nested within paraphyletic crustaceans. However, it is still
      contentious exactly which crustacean taxon is the sister group to Hexapoda. Among
      the favored candidates are Branchiopoda, Malacostraca, Remipedia and Xenocarida
      (Remipedia + Cephalocarida). In this context, we review morphological and
      ultrastructural features of the ovary architecture and oogenesis in these
      crustacean groups in search of traits potentially suitable for phylogenetic
      considerations. We have identified a suite of morphological characters which may
      prove useful in further comparative studies. 

PMID- 24858465
TI  - Biopsy trauma dislodges thymocytes from a thymoma to fill regional lymph node
      sinusoids.
AB  - We present a case of an incisional thymoma biopsy causing dissemination of
      thymocytes to a regional lymph node. Lymphatic seeding from circulating tumor
      cells is a distinct mechanism of tumor spread. We review the literature relevant
      to operative trauma as a cause of tumor cell migration to nearby lymph nodes.
      Summarized are case reports wherein metastasis of benign tumors has been related
      to operative trauma. 

PMID- 24858462
TI  - Interferon alpha plus 13-cis-retinoic acid modulation of BCL-2 plus paclitaxel
      for recurrent small-cell lung cancer (SCLC): an Eastern Cooperative Oncology
      Group study (E6501).
AB  - BACKGROUND: Patients with recurrent small-cell lung cancer (SCLC) have dismal
      outcomes. The failure of salvage therapy is due to the possible development of
      resistance mechanisms, such as the upregulation of the anti-apoptosis protein,
      Bcl-2. We conducted a phase II study to evaluate if modulation of Bcl-2 with 13
      cis-retinoic acid (13-CRA) and interferon alpha could improve response rates when
      combined with paclitaxel in patients with recurrent SCLC. METHODS: Patients with
      recurrent SCLC and measurable disease were treated with interferon alpha at 6
      million units/m2 subcutaneously and 13-CRA 1 mg/kg orally on days 1 and 2 and
      paclitaxel 75 mg/m2 intravenously on day 2 of each week for 6 weeks of an 8-week
      treatment cycle. Treatment was continued until disease progression, development
      of unacceptable toxicity, or withdrawal of consent. The primary endpoint was
      response rate with secondary endpoints of progression-free survival (PFS) and
      overall survival (OS). Bcl-2 levels were assessed in peripheral blood mononuclear
      cells (PBMCs). RESULTS: Thirty-seven patients were enrolled; 34 were included in
      the intention-to-treat analysis as 3 patients were ineligible for the study.
      There were 3 partial responses (9 %), and 5 patients had stable disease (15 %) as
      best response. The median PFS was 2 months, and median OS was 6.2 months.
      Although mean Bcl-2 protein levels decreased with therapy in PBMCs, there was no
      association between Bcl-2 levels and response rate or survival. CONCLUSION:
      Despite sound pre-clinical evidence, the addition of 13-CRA and interferon alpha
      to paclitaxel did not improve outcomes for recurrent SCLC.

PMID- 24858466
TI  - Comparative study of the femoroacetabular impingement (FAI) prevalence in male
      semiprofessional and amateur soccer players.
AB  - INTRODUCTION: Femoroacetabular impingement (FAI) represents a novel approach to
      the mechanical etiology of hip osteoarthritis. The cam-type femoroacetabular
      impingement deformity occurs frequently in young male athletes. The aim of our
      study was to evaluate the prevalence of FAI in male semiprofessional soccer
      players using clinical examination and magnetic resonance imaging (MRI), compared
      to amateur soccer players. In MRI, the alpha angle of Notzli is determined for
      quantifying FAI. MATERIALS AND METHODS: According to power analysis, a total of
      22 asymptomatic semiprofessional soccer players with a median of 23.3 years of
      age (range 18-30 years) and 22 male amateur soccer players with a median of 22.5
      years of age (control group, range 18-29 years) underwent an MRI to measure the
      hip alpha angle of Notzli. The alpha angle of the kicking legs of the
      semiprofessional group and the amateur group were analyzed. The study group was
      moreover evaluated by the Hip Outcome Score (HOS) and a clinical hip examination
      including range of motion (ROM) and impingement tests. RESULTS: In the
      semiprofessional group, 19 soccer players had a right kicking leg and 1 soccer
      player had a left kicking leg. 2 soccer players kicked with two feet. In the semi
      professional group, the mean value of the alpha angle of the kicking leg (57.3 +/
      8.2 degrees ) was significantly higher than in the amateur group (51.7 +/- 4.8
      degrees , P = 0.008). In the semi-professional group, 15 (62.5 %) of 24 kicking
      legs had an increased alpha angle >55 degrees , while 5 (27.3 %) kicking legs of
      the amateur group had an alpha angle >55 degrees . Five semi professional soccer
      players had findings in clinical examination, whereof 4 had an increased alpha
      angle >55 degrees . No participant of the amateur group showed pathological
      results in the clinical examination (P = 0.0484). Overall, semiprofessional
      soccer players had a higher proportion of an increased alpha angle than the
      amateur group. CONCLUSIONS: Semiprofessional players have a higher prevalence of
      an increased alpha angle in the kicking leg than the amateur group at the same
      age. The kicking leg is predisposed for FAI.

PMID- 24858469
TI  - Highly hydrophilic and nonionic poly(2-vinyloxazoline)-grafted silica: a novel
      organic phase for high-selectivity hydrophilic interaction chromatography.
AB  - A new hydrophilic and nonionic poly(2-vinyloxazoline)-grafted silica (Sil-VOX(n))
      phase was synthesized and applied for the separation of nucleosides and
      nucleobases in hydrophilic interaction chromatography (HILIC). Polymerization and
      immobilization onto silica were confirmed by using characterization techniques
      including (1)H NMR spectroscopy, elemental analysis, and diffuse reflectance
      infrared Fourier transform spectroscopy. The hydrophilicity or wettability of Sil
      VOX(n) was observed by measuring the contact angle (59.9 degrees ). The
      chromatographic results were compared with those obtained with a conventional
      HILIC silica column. The Sil-VOX(n) phase showed much better separation of polar
      test analytes than the silica column, and the elution order was different.
      Differences in selectivity between these two columns indicate that the stationary
      phase cannot function merely as an inert support for a water layer into which the
      solutes are partitioned from the bulk mobile phase. To elucidate the interaction
      mechanism, the separation of dihydroxybenzene isomers was performed on both
      columns in normal-phase liquid chromatography. Sil-VOX(n) was very sensitive to
      the dipole moments of the positional isomers of polycyclic aromatic compounds in
      normal-phase liquid chromatography. The interaction mechanism for Sil-VOX(n) in
      HILIC separation is also described.

PMID- 24858467
TI  - Profiling thiol metabolites and quantification of cellular glutathione using FT
      ICR-MS spectrometry.
AB  - We describe preparation and use of the quaternary ammonium-based alpha
      iodoacetamide QDE and its isotopologue *QDE as reagents for chemoselective
      derivatization of cellular thiols. Direct addition of the reagents to live cells
      followed by adduct extraction into n-butanol and analysis by FT-ICR-MS provided a
      registry of matched isotope peaks from which molecular formulae of thiol
      metabolites were derived. Acidification to pH 4 during cell lysis and adduct
      formation further improves the chemoselectivity for thiol derivatization.
      Examination of A549 human lung adenocarcinoma cells using this approach revealed
      cysteine, cysteinylglycine, glutathione, and homocysteine as principal thiol
      metabolites as well as the sulfinic acid hypotaurine. The method is also readily
      applied to quantify the thiol metabolites, as demonstrated here by the
      quantification of both glutathione and glutathione disulfide in A549 cells at
      concentrations of 34.4 +/- 11.5 and 10.1 +/- 4.0 nmol/mg protein, respectively.

PMID- 24858470
TI  - Development of an analytical procedure for quantifying the underivatized
      neurotoxin beta-N-methylamino-L-alanine in brain tissues.
AB  - The cyanotoxin beta-methylamino-L-alanine (BMAA) has received renewed attention
      as an environmental risk factor for sporadic cases of amyotrophic lateral
      sclerosis (ALS) (Nunn et al., Brain Res 410:375-379, 1987). The aim of the
      present study was to develop and to validate an analytical procedure that allows
      the quantification of native BMAA and of its natural isomer, 2,4 diaminobutyric
      acid (DAB), in brain tissues. An analytical procedure was previously reported by
      our group for the determination of underivatized BMAA in environmental samples.
      It included a step of sample clean-up by solid phase extraction (SPE) with a
      mixed-mode sorbent and the analyses were performed by LC/MS-MS using hydrophilic
      interaction chromatography and multiple reactions monitoring scan mode. As brain
      tissues have a higher lipid content, the crucial step of sample clean-up had been
      optimized by evaluating the efficiency of the addition of a liquid/liquid
      extraction step prior to the SPE procedure or alternatively, of washing steps to
      the SPE extraction procedure. The efficiency was checked by visualizing the
      complexity of the resulting chromatograms in LC/MS and their performance by using
      spiked brain samples. The optimized analytical procedure, including a washing
      step with cyclohexane to the SPE with a recovery yield close to 100%, was
      validated using the total error approach and allowed the quantification of BMAA
      in a concentration level ranging from 20 to 1,500 ng/g in brain samples. Finally,
      the feasibility of implementation of this procedure was verified in human brain
      samples from two patients who died of ALS.

PMID- 24858468
TI  - Considerations for accurate gene expression measurement by reverse transcription
      quantitative PCR when analysing clinical samples.
AB  - Reverse transcription quantitative PCR is an established, simple and effective
      method for RNA measurement. However, technical standardisation challenges
      combined with frequent insufficient experimental detail render replication of
      many published findings challenging. Consequently, without adequate consideration
      of experimental standardisation, such findings may be sufficient for a given
      publication but cannot be translated to wider clinical application. This article
      builds on earlier standardisation work and the MIQE guidelines, discussing
      processes that need consideration for accurate, reproducible analysis when
      dealing with patient samples. By applying considerations common to the science of
      measurement (metrology), one can maximise the impact of gene expression studies,
      increasing the likelihood of their translation to clinical tools. 

PMID- 24858474
TI  - The usefulness of the asleep-awake-asleep glioma surgery.

PMID- 24858471
TI  - The dlx5a/dlx6a genes play essential roles in the early development of zebrafish
      median fin and pectoral structures.
AB  - The Dlx5 and Dlx6 genes encode homeodomain transcription factors essential for
      the proper development of limbs in mammalian species. However, the role of their
      teleost counterparts in fin development has received little attention. Here, we
      show that dlx5a is an early marker of apical ectodermal cells of the pectoral fin
      buds and of the median fin fold, but also of cleithrum precursor cells during
      pectoral girdle development. We propose that early median fin fold establishment
      results from the medial convergence of dlx5a-expressing cells at the lateral
      edges of the neural keel. Expression analysis also shows involvement of dlx5a
      during appendage skeletogenesis. Using morpholino-mediated knock down, we
      demonstrate that disrupted dlx5a/6a function results in pectoral fin agenesis
      associated with misexpression of bmp4, fgf8a, and1 and msx genes. In contrast,
      the median fin fold presents defects in mesenchymal cell migration and
      actinotrichia formation, whereas the initial specification seems to occur
      normally. Our results demonstrate that the dlx5a/6a genes are essential for the
      induction of pectoral fin outgrowth, but are not required during median fin fold
      specification. The dlx5a/6a knock down also causes a failure of cleithrum
      formation associated with a drastic loss of runx2b and col10a1 expression. The
      data indicate distinct requirements for dlx5a/6a during median and pectoral fin
      development suggesting that initiation of unpaired and paired fin formation are
      not directed through the same molecular mechanisms. Our results refocus arguments
      on the mechanistic basis of paired appendage genesis during vertebrate evolution.

PMID- 24858473
TI  - Human colorectal CD24+ cancer stem cells are susceptible to epithelial
      mesenchymal transition.
AB  - Conventional cancer chemotherapy preferentially destroys non-stem cancer cells
      within a tumor, and a subpopulation of cancer stem cells (CSCs) is more resistant
      and survives, leading to relapses and metastasis. Howeve, recent studies suggest
      that CD24 and susceptibility to epithelial-mesenchymal transition (EMT) can serve
      as markers of CSCs. We report that CD24(+) cells are susceptible to induction of
      EMT, a phenotype important for cancer metastasis. We studied the responsiveness
      of CSC markers to TGF-beta , an effective EMT inducer. The data on CD24
      demonstrated that CD24(+) cells are susceptible to EMT, a phenotype important for
      cancer metastasis in two colorectal cancer cell lines, the CaR-1 and CCK81.
      CD24(+) cells expressed Notch 1 in response to exposure to TGF-beta in culture
      and showed higher tumorigenic activity compared to controls. This evidence shows
      that CD24(+) cells are susceptible to EMT induction and to cancer progression and
      is indicative of the candidacy of CD24 as a therapeutic target in CSC.

PMID- 24858472
TI  - Fatty acid transport protein 1 (FATP1) localizes in mitochondria in mouse
      skeletal muscle and regulates lipid and ketone body disposal.
AB  - FATP1 mediates skeletal muscle cell fatty acid import, yet its intracellular
      localization and metabolic control role are not completely defined. Here, we
      examine FATP1 localization and metabolic effects of its overexpression in mouse
      skeletal muscle. The FATP1 protein was detected in mitochondrial and plasma
      membrane fractions, obtained by differential centrifugation, of mouse
      gastrocnemius muscle. FATP1 was most abundant in purified mitochondria, and in
      the outer membrane and soluble intermembrane, but not in the inner membrane plus
      matrix, enriched subfractions of purified mitochondria. Immunogold electron
      microscopy localized FATP1-GFP in mitochondria of transfected C2C12 myotubes.
      FATP1 was overexpressed in gastrocnemius mouse muscle, by adenovirus-mediated
      delivery of the gene into hindlimb muscles of newborn mice, fed after weaning a
      chow or high-fat diet. Compared to GFP delivery, FATP1 did not alter body weight,
      serum fed glucose, insulin and triglyceride levels, and whole-body glucose
      tolerance, in either diet. However, fatty acid levels were lower and beta
      hydroxybutyrate levels were higher in FATP1- than GFP-mice, irrespective of diet.
      Moreover, intramuscular triglyceride content was lower in FATP1- versus GFP-mice
      regardless of diet, and beta-hydroxybutyrate content was unchanged in high-fat
      fed mice. Electroporation-mediated FATP1 overexpression enhanced palmitate
      oxidation to CO2, but not to acid-soluble intermediate metabolites, while CO2
      production from beta-hydroxybutyrate was inhibited and that from glucose
      unchanged, in isolated mouse gastrocnemius strips. In summary, FATP1 was
      localized in mitochondria, in the outer membrane and intermembrane parts, of
      mouse skeletal muscle, what may be crucial for its metabolic effects.
      Overexpressed FATP1 enhanced disposal of both systemic fatty acids and
      intramuscular triglycerides. Consistently, it did not contribute to the high-fat
      diet-induced metabolic dysregulation. However, FATP1 lead to hyperketonemia,
      likely secondary to the sparing of ketone body oxidation by the enhanced
      oxidation of fatty acids. 

PMID- 24858476
TI  - Bionanoconjugation for proteomics applications - An overview.
AB  - Formed as an interdisciplinary domain on the basis of Human Genome Project,
      Proteomics aims at the large-scale study of proteins. The enthusiasm that
      resulted from obtaining the complete human genetic information has, however, been
      chastened by the realization that this information contributes little to the
      comprehension and knowledge of the expressed proteins. In the wake of this
      realization, the Human Proteome Project (HUPO) was founded, which is a global,
      collaborative initiative, aiming at the complete characterization of the proteins
      of all protein-coding genes. Nonetheless, the rapid detection of these molecules
      in complex biological samples under conditions considered to be of clinical
      relevance is extremely difficult, requiring the development of very sensitive,
      robust, reproducible and high throughput platforms. Nanoproteomics has emerged as
      a feasible, promising option, offering short assay times, low sample consumption,
      ultralow detection and high throughput capacity. Additionally, the successful
      synthesis of biomolecules and nanoparticle hybrids yields systems which often
      exhibit new or improved features. Herein, we overview the recent advances in
      bioconjugation at the nanolevel and, specifically, their application in
      Proteomics, discussing not only the merits and prospects of Proteomics, but also
      present day limitations. 

PMID- 24858477
TI  - WITHDRAWN: Flavonoid glycosylation and biological benefits.
AB  - This article has been withdrawn at the request of the editor. The Publisher
      apologizes for any inconvenience this may cause. The full Elsevier Policy on
      Article Withdrawal can be found at
      http://www.elsevier.com/locate/withdrawalpolicy.

PMID- 24858478
TI  - Three-dimensional biomaterial degradation - Material choice, design and extrinsic
      factor considerations.
AB  - The apparent difficulty to precisely control fine-tuning of biomaterial
      degradation has initiated the recent paradigm shift from conventional top-down
      fabrication methods to more nature-inspired bottom-up assemblies. Sophistication
      of material fabrication techniques allows today's scientists to reach beyond
      conventional natural materials in order to synthesise tomorrow's 'designer
      material'. Material degradation into smaller components and subsequent release of
      encapsulated cells or cell-signalling agents have opened medically exploitable
      avenues, transforming the area of regenerative medicine into a dynamic and self
      propagating branch of modern medicine. The aim to synthesise ever more refined
      scaffolding structures in order to create micro- and nanoenvironments resembling
      those found in natural tissues now represents an ever growing niche in the
      materials sciences. Recently, we have developed and conducted the world's first
      in-human tracheal transplantation using a non-degradable completely synthetic
      biomaterial. Fuelled by such clinical potential, we are currently developing a
      biodegradable version suitable for skin tissue engineering and paediatric
      applications. However, despite enormous efforts, current, as yet insurmountable
      challenges include precise biomaterial degradation within pre-determined spatial
      and temporal confines in an effort to release bio-signalling agents in such
      orchestrated fashion as to fully regenerate functioning tissues. In this review,
      the authors, almost anti-climactically, ask the readers to step out of the
      artificially over-constructed spiral of ever more convoluted scaffold fabrication
      techniques and consider the benefits of controllable bottom-up scaffold
      fabrication methods. It will further be investigated how scaffold designs and
      fabrication methods may influence degradation and subsequent release of
      incorporated elements. A focus will be placed on the delivery of growth factors,
      stem cells and therapeutic agents alone or in parallel. The difficulties of
      designing a delivery vehicle capable of delivering multiple factors whilst
      maintaining distinct release kinetics will be highlighted. Finally, this review
      will be rounded off with an insight into current literature addressing the
      recurring issues of degradation product toxicities and suggests means of
      overcoming those. 

PMID- 24858480
TI  - Anticipated and actual reactions to receiving HIV positive results through self
      testing among gay and bisexual men.
AB  - We explored anticipated and actual reactions to receiving HIV positive results
      through self-testing with a diverse group of 84 gay and bisexual men in New York
      City. Grounded Theory was used to investigate these reactions in a two-phase
      study, one hypothetical, followed by a practical phase in which self-tests were
      distributed and used. Three major themes emerged when participants were asked
      about their anticipated reactions to an HIV positive self-test result: managing
      emotional distress, obtaining HIV medical care, and postponing sexual activity.
      When participants were asked about their anticipated reactions to a partner's HIV
      positive self-test result, five themes emerged: provide emotional support;
      refrain from engaging in sex with casual partner; avoid high-risk sexual activity
      with both main and casual partners; seek medical services; and obtain a
      confirmatory test result. Although none of the participants tested positive,
      seven of their partners did. Participants provided emotional support and linked
      their partners to support services. The availability of HIV self-testing kits
      offers potential opportunities to tackle HIV infection among individuals with
      high-risk practices.

PMID- 24858479
TI  - Low PTEN expression is associated with worse overall survival in head and neck
      squamous cell carcinoma patients treated with chemotherapy and cetuximab.
AB  - BACKGROUND: Platinum-based chemotherapy associated with cetuximab is the first
      line treatment for inoperable recurrence or metastatic head and neck squamous
      cell carcinoma (HNSCC). There is no established biomarker for cetuximab efficacy
      in HNSCC. The PI3K pathway is one of the most frequently altered pathways in
      HNSCC. Loss of phosphatase and tensin homolog (PTEN) expression occurs in up to
      30 % of cases. METHODS: This was a retrospective analysis of data from 61
      patients with inoperable recurrence or metastatic HNSCC treated with cetuximab.
      PTEN, epidermal growth factor receptor and p16 expression were analyzed by
      immunohistochemistry and tested for association with clinical outcomes. RESULTS:
      Median overall survival was 11.4 months and progression-free survival was 6.9
      months. Low PTEN expression was present in 26.2 % of patients and identified
      patients with worse prognosis. p16 was positive in only 8.5 % of tumors.
      CONCLUSIONS: Low PTEN expression in patients treated with cetuximab plus
      chemotherapy emerged as a prognostic biomarker and should be evaluated for its
      predictive role for cetuximab efficacy.

PMID- 24858481
TI  - Rectal-specific microbicide applicator: evaluation and comparison with a vaginal
      applicator used rectally.
AB  - An applicator designed for rectal delivery of microbicides was tested for
      acceptability by 95 young men who have sex with men, who self-administered 4 mL
      of placebo gel prior to receptive anal intercourse over 90 days. Subsequently, 24
      of the participants self-administered rectally 4 mL of tenofovir or placebo gel
      over 7 days using a vaginal applicator, and compared both applicators on a Likert
      scale of 1-10, with 10 the highest rating. Participants reported high likelihood
      to use either applicator in the future (mean scores 9.3 and 8.8 respectively, p =
      ns). Those who tested both liked the vaginal applicator significantly more than
      the rectal applicator (7.8 vs. 5.2, p = 0.003). Improvements in portability,
      conspicuousness, aesthetics, tip comfort, product assembly and packaging were
      suggested for both. This rectal-specific applicator was not superior to a vaginal
      applicator. While likelihood of future use is reportedly high, factors that
      decrease acceptability may erode product use over time in clinical trials.
      Further attention is needed to develop user-friendly, quick-acting rectal
      microbicide delivery systems.

PMID- 24858482
TI  - How to increase the utilization of donor hearts?
AB  - Cardiac transplantation is the best treatment available for patients with end
      stage cardiomyopathy. Shortage of donor hearts is the main factor limiting the
      use of this treatment. Many donor hearts are rejected for transplantation because
      of left ventricular (LV) systolic dysfunction and/or wall motion abnormalities.
      While some donors have true cardiomyopathy, a significant proportion has
      reversible LV dysfunction due to neurogenic stunned myocardium. This condition is
      triggered by excess of catecholamines, which is typical for brain-dead donors. If
      given time to recover, LV function may improve, and the heart will be suitable
      for transplantation. Moreover, limiting of exogenous catecholamines may
      facilitate the recovery. In this review, we summarize the data on LV
      dysfunction/wall motion abnormalities in heart donors and propose the strategy to
      increase the utilization of donor hearts. 

PMID- 24858484
TI  - Gtpbp2 is required for BMP signaling and mesoderm patterning in Xenopus embryos.
AB  - Smad proteins convey canonical intracellular signals for activated receptors in
      the TGFbeta superfamily, but the activity of Smads and their impact on target
      genes are further regulated by a wide variety of cofactors and partner proteins.
      We have identified a new Smad1 partner, a GTPase named Gtpbp2 that is a distant
      relative of the translation factor eEf1a. Gtpbp2 affects canonical signaling in
      the BMP branch of the TGFbeta superfamily, as morpholino knockdown of Gtpbp2
      decreases, and overexpression of Gtpbp2 enhances, animal cap responses to BMP4.
      During Xenopus development, gtpbp2 transcripts are maternally expressed and
      localized to the egg animal pole, and partitioned into the nascent ectodermal and
      mesodermal cells during cleavage and early gastrulation stages. Subsequently,
      gtpbp2 is expressed in the neural folds, and in early tadpoles undergoing
      organogenesis gtpbp2 is expressed prominently in the brain, eyes, somites,
      ventral blood island and branchial arches. Consistent with its expression,
      morpholino knockdown of Gtpbp2 causes defects in ventral-posterior germ layer
      patterning, gastrulation and tadpole morphology. Overexpressed Gtpbp2 can induce
      ventral-posterior marker genes and localize to cell nuclei in Xenopus animal
      caps, highlighting its role in regulating BMP signaling in the early embryo.
      Here, we introduce this large GTPase as a novel factor in BMP signaling and
      ventral-posterior patterning. 

PMID- 24858485
TI  - Integrin-alpha5beta1 is not required for mural cell functions during development
      of blood vessels but is required for lymphatic-blood vessel separation and
      lymphovenous valve formation.
AB  - Integrin alpha5beta1 is essential for vascular development but it remains unclear
      precisely where and how it functions. Here, we report that deletion of the gene
      encoding the integrin-alpha5 subunit (Itga5) using the Pdgfrb-Cre transgenic
      mouse line, leads to oedema, haemorrhage and increased levels of embryonic
      lethality. Unexpectedly, these defects were not caused by loss of alpha5 from
      Pdgfrb-Cre expressing mural cells (pericytes and vascular smooth muscle cells),
      which wrap around the endothelium and stabilise blood vessels, nor by defects in
      the heart or great vessels, but were due to abnormal development of the lymphatic
      vasculature. Reminiscent of the pathologies seen in the human lymphatic
      malformation, fetal cystic hygroma, alpha5 mutants display defects both in the
      separation of their blood and lymphatic vasculature and in the formation of the
      lymphovenous valves. As a consequence, alpha5-deficient mice develop dilated,
      blood-filled lymphatic vessels and lymphatic capillaries that are ectopically
      covered with smooth muscle cells. Analysis of the expression of Pdgfrb during
      lymphatic development suggests that these defects probably arise from loss of
      alpha5beta1 integrin in subsets of specialised Prox1(+)Pdgfrb(+) venous
      endothelial cells that are essential for the separation of the jugular lymph sac
      from the cardinal vein and formation of the lymphovenous valve leaflets. 

PMID- 24858487
TI  - Timing of cisplatin administration for chemoradiotherapy in transgenic mice
      bearing lens tumors.
AB  - Cisplatin-based concurrent chemoradiotherapy (CCRT) has become a standard
      treatment for cancer of the uterine cervix. However, there have been no
      investigations into the optimum timing for administration of anticancer drugs
      using animal models. The aim of the present study was to determine the
      appropriate timing for administration of the anticancer drug cisplatin in
      relation to delivery of radiation by assessing the antitumor activity and adverse
      effects of 3 different regimens in alphaT3 transgenic mice bearing lens
      epithelial tumors. CCRT showed the strongest antitumor activity. There was a
      significant difference between CCRT and administration of cisplatin before
      radiotherapy (neoadjuvant therapy) with regard to the apoptotic effect detected
      by TUNEL staining, but there was no significant difference between CCRT and
      administration of cisplatin after radiotherapy (adjuvant therapy). Assessment of
      adverse effects showed that there were no significant differences in the
      mortality rate, weight loss, anemia and leukopenia among the 3 regimens. In
      conclusion, these findings obtained in an animal model suggest that cisplatin
      should probably not be administered before irradiation, since the antitumor
      effect is significantly weaker than that of CCRT or administration after
      irradiation, while adverse effects are similar. 

PMID- 24858488
TI  - Neurotoxicity in breast cancer survivors >=10 years post-treatment is dependent
      on treatment type.
AB  - Adjuvant chemotherapy (CT) for breast cancer (BC) is associated with very late
      side-effects on brain function and structure. However, little is known about
      neurotoxicity of specific treatment regimens. To compare neurotoxicity profiles
      after different treatment strategies, we used neurocognitive testing and
      multimodality MRI in BC survivors randomized to high-dose (HI), conventional-dose
      (CON-) CT or radiotherapy (RT) only and a healthy control (HC) group. BC
      survivors who received CON-CT (n = 20) and HC (n = 20) were assessed using a
      neurocognitive test battery and multimodality MRI including 3D-T1, Diffusion
      Tensor Imaging (DTI) and 1H-MR spectroscopy (1H-MRS) to measure various aspects
      of cerebral white (WM) and gray matter (GM). Data were compared to previously
      assessed groups of BC survivors who received HI-CT (n = 17) and RT-only (n = 15).
      Testing took place on average 11.5 years post-CT. 3D-T1 showed focal GM volume
      reductions both for HI-CT and CON-CT compared to RT-only (p < .004). DTI-derived
      mean diffusivity and 1H-MRS derived N-acetyl aspartate showed WM injury specific
      to HI-CT but not CON-CT (p < .05). Residual effects were revealed in the RT-only
      group compared to HC on MRI and neurocognitive measurements (p < .05). Ten years
      after adjuvant CT for BC lower cerebral GM volume was found in HI as well as CON
      CT BC survivors whereas injury to WM is restricted to HI-CT. This might indicate
      that WM brain changes after BC treatment may show more pronounced (partial)
      recovery than GM. Furthermore, our results suggest residual neurotoxicity in the
      RT-only group, which warrants further investigation. 

PMID- 24858486
TI  - miR-203 regulates progenitor cell proliferation during adult zebrafish retina
      regeneration.
AB  - Damage of the zebrafish retina triggers a spontaneous regeneration response that
      is initiated by Muller Glia (MG) dedifferentiation and asymmetric cell division
      to produce multipotent progenitor cells. Subsequent expansion of the progenitor
      pool by proliferation is critical for retina regeneration. Pax6b expression in
      the progenitor cells is necessary for their proliferation, but exact regulation
      of its expression is unclear. Here, we show that miR-203 is downregulated during
      regeneration in proliferating progenitor cells. Elevated miR-203 levels inhibit
      progenitor cell expansion without affecting MG dedifferentiation or progenitor
      cell generation. Using GFP-reporter assays and gain and loss of function
      experiments in the retina, we show that miR-203 expression must be suppressed to
      allow pax6b expression and subsequent progenitor cell proliferation. 

PMID- 24858490
TI  - Lessons learnt from the DDIExtraction-2013 Shared Task.
AB  - The DDIExtraction Shared Task 2013 is the second edition of the DDIExtraction
      Shared Task series, a community-wide effort to promote the implementation and
      comparative assessment of natural language processing (NLP) techniques in the
      field of the pharmacovigilance domain, in particular, to address the extraction
      of drug-drug interactions (DDI) from biomedical texts. This edition has been the
      first attempt to compare the performance of Information Extraction (IE)
      techniques specific for each of the basic steps of the DDI extraction pipeline.
      To attain this aim, two main tasks were proposed: the recognition and
      classification of pharmacological substances and the detection and classification
      of drug-drug interactions. DDIExtraction 2013 was held from January to June 2013
      and attracted wide attention with a total of 14 teams (6 of the teams
      participated in the drug name recognition task, while 8 participated in the DDI
      extraction task) from 7 different countries. For the task of the recognition and
      classification of pharmacological names, the best system achieved an F1 of 71.5%,
      while, for the detection and classification of DDIs, the best result was an F1 of
      65.1%. The results show advances in the state of the art and demonstrate that
      significant challenges remain to be resolved. This paper focuses on the second
      task (extraction of DDIs) and examines its main challenges, which have yet to be
      resolved. 

PMID- 24858491
TI  - Intelligent mobile support for therapy adherence and behavior change.
AB  - Mobile applications have proven to be promising tools for supporting people in
      adhering to their health goals. Although coaching and reminder apps abound, few
      of them are based on established theories of behavior change. In the present
      work, a behavior change support system is presented that uses a computational
      model based on multiple psychological theories of behavior change. The system
      determines the user's reason for non-adherence using a mobile phone app and an
      online lifestyle diary. The user automatically receives generated messages with
      persuasive, tailored content. The system was designed to support chronic patients
      with type 2 diabetes, HIV, and cardiovascular disease, but can be applied to many
      health and lifestyle domains. The main focus of this work is the development of
      the model and the underlying reasoning method. Furthermore, the implementation of
      the system and some preliminary results of its functioning will be discussed. 

PMID- 24858492
TI  - A convenient nucleic acid test on the basis of the capillary convective PCR for
      the on-site detection of enterovirus 71.
AB  - The recent and continuing epidemic of enterovirus 71 in China has affected
      millions of children and resulted in thousands of deaths. Timely diagnosis and
      management is essential for disease control. Current enterovirus 71 molecular
      tests require resources that are unavailable for on-site testing. We have
      developed a simple-to-operate nucleic acid test, the convenient and integrated
      nucleic acid test, for local medical institutions. It uses a convective PCR for
      rapid amplification, a dipstick for visual detection of PCR products, and a
      simple commercial kit for nucleic acid extraction. By using a specially designed
      reagent and reaction tube containing a dipstick, the amplification and detection
      processes are well integrated and simplified. Moreover, cross contamination that
      may be caused by an open-tube detection system can be avoided. On the basis of
      the convenient and integrated nucleic acid test, an enterovirus 71 assay for on
      site testing was developed. After evaluating known hand, foot, and mouth disease
      virus stocks of 17 strains of 11 different serotypes, this assay showed a
      favorable detection spectrum and no cross-reactivity. Its clinical performance
      was established by testing 141 clinical samples and comparing the results with a
      nested RT-PCR method. The assay showed a clinical sensitivity and specificity of
      98.5% and 100%, respectively. Our results suggest that this convenient and
      integrated nucleic acid test enterovirus 71 assay may serve as an on-site
      diagnosis tool. 

PMID- 24858493
TI  - Highly efficient differentiation of embryonic stem cells into adipocytes by
      ascorbic acid.
AB  - Adipocyte differentiation and function have become the major research targets due
      to the increasing interest in obesity and related metabolic conditions. Although,
      late stages of adipogenesis have been extensively studied, the early phases
      remain poorly understood. Here we present that supplementing ascorbic acid (AsA)
      to the adipogenic differentiation cocktail enables the robust and efficient
      differentiation of mouse embryonic stem cells (mESCs) to mature adipocytes. Such
      ESC-derived adipocytes mimic the gene-expression profile of subcutaneous isolated
      adipocytes in vivo remarkably well, much closer than 3T3-L1 derived ones.
      Moreover, the differentiated cells are in a monolayer, allowing a broad range of
      genome-wide studies in early and late stages of adipocyte differentiation to be
      performed. 

PMID- 24858494
TI  - Interaction of adult human neural crest-derived stem cells with a nanoporous
      titanium surface is sufficient to induce their osteogenic differentiation.
AB  - Osteogenic differentiation of various adult stem cell populations such as neural
      crest-derived stem cells is of great interest in the context of bone
      regeneration. Ideally, exogenous differentiation should mimic an endogenous
      differentiation process, which is partly mediated by topological cues. To
      elucidate the osteoinductive potential of porous substrates with different pore
      diameters (30 nm, 100 nm), human neural crest-derived stem cells isolated from
      the inferior nasal turbinate were cultivated on the surface of nanoporous
      titanium covered membranes without additional chemical or biological
      osteoinductive cues. As controls, flat titanium without any topological features
      and osteogenic medium was used. Cultivation of human neural crest-derived stem
      cells on 30 nm pores resulted in osteogenic differentiation as demonstrated by
      alkaline phosphatase activity after seven days as well as by calcium deposition
      after 3 weeks of cultivation. In contrast, cultivation on flat titanium and on
      membranes equipped with 100 nm pores was not sufficient to induce osteogenic
      differentiation. Moreover, we demonstrate an increase of osteogenic transcripts
      including Osterix, Osteocalcin and up-regulation of Integrin beta1 and alpha2 in
      the 30 nm pore approach only. Thus, transplantation of stem cells pre-cultivated
      on nanostructured implants might improve the clinical outcome by support of the
      graft adherence and acceleration of the regeneration process.

PMID- 24858496
TI  - Evaluation of bread crumbs as a potential carbon source for the growth of
      thraustochytrid species for oil and omega-3 production.
AB  - The utilization of food waste by microorganisms to produce omega-3 fatty acids or
      biofuel is a potentially low cost method with positive environmental benefits. In
      the present study, the marine microorganisms Thraustochytrium sp. AH-2 and
      Schizochytrium sp. SR21 were used to evaluate the potential of breadcrumbs as an
      alternate carbon source for the production of lipids under static fermentation
      conditions. For the Thraustochytrium sp. AH-2, submerged liquid fermentation with
      3% glucose produced 4.3 g/L of biomass and 44.16 mg/g of saturated fatty acids
      after seven days. Static fermentation with 0.5% and 1% breadcrumbs resulted in
      2.5 and 4.7 g/L of biomass, and 42.4 and 33.6 mg/g of saturated fatty acids,
      respectively. Scanning electron microscopic (SEM) studies confirmed the growth of
      both strains on breadcrumbs. Attenuated total reflection Fourier transform
      infrared (ATR-FTIR) spectroscopy for both strains were consistent with the
      utilization of breadcrumbs for the production of unsaturated lipids, albeit at
      relatively low levels. The total lipid yield for static fermentation with bread
      crumbs was marginally lower than that of fermentation with glucose media, while
      the yield of unsaturated fatty acids was considerably lower, indicating that
      static fermentation may be more appropriate for the production of biodiesel than
      for the production of omega-3 rich oils in these strains. 

PMID- 24858495
TI  - Consumption of sugar-sweetened beverages is associated with components of the
      metabolic syndrome in adolescents.
AB  - Sugar-sweetened beverages (SSBs) are the principle source of added sugar in
      diets. Cardiometabolic disturbances can occur from early childhood to adulthood.
      The aim of this cross-sectional study was to examine the gender-specific
      association of SSB intake with metabolic syndrome (MetS) and its components among
      adolescents in Taiwan. A total of 2727 adolescents aged 12 to 16 years randomly
      selected from three diverse economic areas in Southern Taiwan by using a
      multistage-sampling strategy participated in this study. Demographic, dietary,
      physical and anthropometric parameters were measured, and serum lipid profiles
      and glucose levels were determined. The International Diabetes Federation (IDF)
      specifies that MetS requires abdominal obesity and >=2 abnormal components, and
      Cook criteria for MetS require >=3 abnormal components. We applied survey-data
      modules to data analyses, and used multiple regression and logistic models to
      adjust for covariates. An increased SSB intake was linked to a greater waist
      circumference in both sexes and to systolic blood pressure in boys (P for trend:
      <=0.043). Male moderate and high consuming SSB drinkers exhibited triglyceride
      levels that were 8.0 and 8.2 mg/dL significantly higher, respectively, than those
      of nondrinkers. Compared with nondrinkers, boys who consumed >500 mL/day (high
      quantity) of SSBs exhibited 10.3-fold (95% confidence intervals (CIs): 1.2-90.2)
      and 5.1-fold (95% CIs: 1.01-25.5) risks of contracting MetS, as defined by the
      IDF and Cook criteria for MetS, respectively. In girls, the risk estimates for
      the same comparison were not significant by the IDF criteria (6.5-fold risk, 95%
      CIs: 0.9-infinity) or Cook criteria (5.9-fold risk, 95% CIs: 0.8-43.8) for MetS.
      High SSB consumption was also linked to 1.9-fold (95% CIs: 1.1-3.1) and 2.7-fold
      (95% CIs: 1.3-5.7) higher risks of being at a greater overall metabolic risk in
      girls and boys, respectively. In conclusion, a high SSB intake is associated with
      adolescent MetS among boys but not girls in Taiwan. 

PMID- 24858497
TI  - Antioxidant activity in extracts of 27 indigenous Taiwanese vegetables.
AB  - The objectives of this study were to identify the antioxidants and antioxidant
      axtivity in 27 of Taiwan's indigenous vegetables. Lycium chinense (Lc), Lactuca
      indica (Li), and Perilla ocymoides (Po) contained abundant quercetin (Que), while
      Artemisia lactiflora (Al) and Gynura bicolor (Gb) were rich in morin and
      kaempferol, respectively. Additionally, Nymphoides cristata (Nc) and Sechium
      edule (Se)-yellow had significantly higher levels of myricetin (Myr) than other
      tested samples. Cyanidin (Cyan) and malvidin (Mal) were abundant in Gb,
      Abelmoschus esculentus Moench (Abe), Po, Anisogonium esculentum (Retz.) Presl
      (Ane), Ipomoea batatas (Ib)-purple, and Hemerocallis fulva (Hf)-bright orange.
      Relatively high levels of Trolox equivalent antioxidant capacity (TEAC), oxygen
      radical absorption capacity (ORAC), and 1,1-diphenyl-2-picryl-hydrazyl (DPPH)
      radical scavenger were generated from extracts of Toona sinensis (Ts) and Po.
      Significant and positive correlations between antioxidant activity and
      polyphenols, anthocyanidins, Que, Myr, and morin were observed, indicating that
      these phytochemicals were some of the main components responsible for the
      antioxidant activity of tested plants. The much higher antioxidant activity of
      Po, Ts, and Ib (purple leaf) may be related to their higher Cyan, Que, and
      polyphenol content. 

PMID- 24858500
TI  - Epigenetic changes caused by intrauterine malnutrition as potential disease
      mediator and early prevention in developmental stages.
AB  - Presently, the incidences of noncommunicable diseases (NCD) have been increasing
      in both low- and middle-income countries worldwidely. Effective long-term and
      multigeneration interventions to decrease the risk of NCD should be developed and
      introduced. The environment in utero alters phenotypes mainly through epigenetic
      mechanisms. The epigenetic changes induced in an unfavorable developmental
      environment have lifelong effects on cardiovascular and metabolic functions,
      susceptibility to cardiovascular disease, obesity, and other NCD. Although
      compared with animals, epigenetic analysis of human specimens is restricted
      except for peripheral blood, placental, or umbilical specimens, recently,
      important human studies have been reported concerning the epigenetic analysis of
      Line 1 gene from the umbilical blood, umbilical RXRalpha, or the peripheral
      nuclear cell IGF-2. The birth weight is an indirect marker of in-the-womb
      nutritional status. The incidence of low-birth-weight infants, weighing less than
      2,500 g, has been increasing in Japan. Presently, it is higher than that in the
      latter half of the 20 s of the Showa era, and is the highest among the OECD
      countries. This trend suggests that in Japan the intrauterine nutritional status
      has been deteriorating. We have to change this trend and put much attention on
      the prepregnancy and pregnancy nutrition for the present and future generations.

PMID- 24858501
TI  - Effects of exposure to Di(2-ethylhexyl)phthalate ?during fetal period on next
      generation.
AB  - The concept of the Developmental Origins of Health and Disease (DOHaD) is
      bringing new insights into the origin of lifestyle diseases: unbalanced nutrition
      in utero and during infancy is associated with an increased risk of lifestyle
      diseases. In order to clarify this association, experimental and epidemiological
      studies have been conducted. Maternal exposure to di(2-ethylhexyl)phthalate
      (DEHP), an agonist of peroxisome proliferator-activated receptor alpha
      (PPARalpha), decreases the number of live fetuses and newborn pups, and their
      body weights, and it enhances fetal desorption in wild-type mice. Similarly,
      these DEHP were also observed in mice expressing human PPARalpha, but not in
      PPARalpha-null mice. These results suggest that the DEHP toxicity in offspring is
      caused dependently on PPARalpha. DEHP suppresses the increase in the levels of
      plasma triglyceride (TG)/fatty acids (FAs) only in wild-type pregnant mice,
      suggesting that the decreased lipid levels in utero may affect the fetus
      development, because TG/FAs are essential in the development of fetuses.
      Additionally, maternal DEHP exposure decreases estrogen and progesterone
      balances, which may also explain the effects on fetuses and pups mentioned above.
      Indeed, DEHP itself or metabolite(s) may induce the toxicity, because a
      difference in the metabolic route is observed between the wild-type and PPARalpha
      null mice. Thus, we were unable to conclude the causal factor(s) for the DEHP
      induced offspring toxicity, that is, whether it is a direct or an indirect effect
      of the chemical or metabolite(s) via the toxic effects on maternal mice; however,
      PPARalpha is indeed associated with in offspring toxicity.

PMID- 24858502
TI  - Increase in incidence of hepatic tumors caused by oncogenic somatic mutation in
      mice maternally exposed to inorganic arsenic and the multigenerational and
      transgenerational effects of inorganic arsenic.
AB  - Inorganic arsenic is a natural environmental contaminant and known to be a human
      carcinogen. Although rodent models are pivotal in elucidating the mode of action
      of arsenic, it has been difficult to verify the carcinogenicity of arsenic in
      rodents until recently. Waalkes et al. (Toxicol Appl Pharmacol 2003;?186:7-17)
      reported that maternal exposure to arsenite increases the incidence of hepatic
      tumors in the male pups of C3H mice in adulthood. This finding indicated that the
      gestational period is vulnerable to arsenic. Using the same experimental model,
      we found that maternal arsenite exposure increases the incidence of hepatic
      tumors caused by a somatic mutation of the C61A Ha-ras gene, which encodes an
      activated oncogenic Ha-ras protein. The G:C to T:A transversion is attributable
      to oxidative stress. Our further studies of gpt delta transgenic mice, which
      enable detection of in vivo mutation, and genome-wide analysis of DNA methylation
      levels using the methylated DNA immunoprecipitation-CpG island microarray method
      suggest that oxidative-stress-induced mutation and DNA methylation changes are
      involved in the tumor augmentation in the pups maternally exposed to arsenic. Our
      recent study has also suggested that maternal arsenic exposure increases the
      incidence of hepatic tumors even in the grandchildren (the F2 generation).
      Consideration should be given to multigenerational and transgenerational effects
      of maternal exposure in future studies.

PMID- 24858498
TI  - Endothelial activation and chemoattractant expression are early processes in
      isolated blast brain injury.
AB  - Blast injuries are an increasing problem in military conflicts and terrorist
      incidents. Blast-induced traumatic brain injury has risen to prominence and
      represents a specific form of primary brain injury, with sufficiently different
      physical attributes (and possibly biological consequences) to be classified
      separately. There is increasing interest in the role of blast in initiating
      inflammatory responses, which may be linked to the pathological processes seen
      clinically. Terminally anaesthetised rats were exposed to a blast wave directed
      at the cranium, using a bench-top blast wave generator. Control animals were not
      exposed to blast. Animals were killed after 8 h, and the brains examined for
      evidence of an inflammatory response. Compared to controls, erythropoietin,
      endothelial integrins, ICAM and sVCAM, and the pro-inflammatory cytokine,
      monocyte chemoattractant protein-1 (MCP-1) were significantly elevated. Other pro
      inflammatory cytokines, including MIP-1alpha, were also detectable, but levels
      did not permit accurate quantification. Six inflammatory genes examined by qRT
      PCR exhibited a biologically significant increase in activity in the blast
      exposed animals. These included genes supporting chemokines responsible for
      monocyte recruitment, including MCP-1, and chemokines influencing T cell
      movement. Brain injury is usually accompanied by pathological neuro-inflammation.
      This study shows that blast brain injury is no exception, and the data provide
      important mechanistic clues regarding the drivers of such inflammation. Whilst
      this effect alone is unlikely to be responsible for the totality of consequences
      of blast brain injury, it suggests a mechanism that may be priming the cerebral
      inflammatory response and rendering cerebral tissue more susceptible to the
      deleterious effects of systemic inflammatory reactions. 

PMID- 24858504
TI  - Physiological and psychological effects of walking in stay-in forest therapy.
AB  - OBJECTIVE: To provide scientific evidence of the physiological and psychological
      effects of forest and urban environments on 47 young male adults undergoing stay
      in forest therapy. METHODS: Field experiments were conducted at four sites in
      Japan. At each site, 12 subjects participated in the experiment. The experiments
      were conducted in forest and urban environments, and the subjects' physiological
      and psychological responses to these environments were compared. On the first
      day, six subjects were sent to a forest area, and the other six were sent to an
      urban area as controls. The groups were switched the next day. Heart rate
      variability and heart rate were measured to assess physiological responses. The
      semantic differential method for assessing emotions, the reports of "refreshed"
      feeling, and the Profile of Mood States (POMS) were used to assess psychological
      responses. The physiological and psychological responses of each subject were
      recorded during and after walking, and the differences in indices were compared
      between the two environments. RESULTS: The forest environment was associated with
      a higher parasympathetic nervous activity, a lower sympathetic nervous activity,
      and a lower heart rate than the urban environment. The subjective evaluation
      scores were generally in accordance with the physiological reactions and were
      significantly higher in the forest environment than in the urban environment.
      POMS measurements showed that the forest environment was psychologically relaxing
      and enhanced psychological vigor. CONCLUSIONS: This study provided clear
      scientific evidence of the physiological effects of forest therapy. The results
      will contribute to the development of forest therapy research and support the
      inclusion of forest therapy in preventive medicine.

PMID- 24858505
TI  - Physiological and psychological effects of viewing forest landscapes in a seated
      position in one-day forest therapy experimental model.
AB  - OBJECTIVES: To clarify the physiological and psychological effects of a one-day
      forest therapy. METHODS: The experiments were conducted at three sites, each
      containing a forest area and an urban area in Japan. Twelve male students
      participated at each of the three venues (total, 36 subjects). The subjects were
      randomly assigned to visit either the forest or urban area and were instructed to
      view the scenery in a seated position for 15 min. Heart rate variability and
      heart rate were measured to assess physiological response. The semantic
      differential method, reports of "refreshed" feeling, "state anxiety" in the State
      Trait Anxiety Inventory (STAI) and Profile of Mood States (POMS) were used to
      determine psychological responses. RESULTS: Physiological data revealed that the
      subjects demonstrated significantly different responses to the forest and urban
      environments. For heart rate variability, the subjects showed a significantly
      higher ln(HF) and a lower ln(LF/HF) in the forest environment than in the urban
      environment. Heart rate decreased in the forest environment relative to that in
      the urban environment. The forest environment was perceived as significantly more
      "comfortable," "soothing," and "natural" than the urban environment after
      viewing. The score for "refreshed" feeling was also significantly higher. The
      score for the "state anxiety" in STAI was significantly reduced by viewing the
      scenery in the forested areas. The score for the "vigor" subscale of the POMS was
      significantly improved by viewing the scenery in the forested areas, whereas
      scores for negative feelings, such as "tension-anxiety" and "fatigue," were
      significantly reduced. CONCLUSIONS: These results provided scientific evidence of
      the physiological and psychological effects of a one-day forest therapy.

PMID- 24858506
TI  - Elucidation of the physiological adjustment effect of forest therapy.
AB  - OBJECTIVES: The aim of this study was to elucidate the physiological adjustment
      effect of forest therapy based on the Law of Initial Value. METHODS: The
      experiments were conducted in nine forest and urban areas in Japan during the
      period from 2011 to 2012. There were 12 male Japanese university students
      participating in each of the nine experiments (total, 108 participants). Of
      these, 98 subjects (mean age +/- standard deviation, 21.4 +/- 1.6 years) were
      analyzed. The subjects were instructed to view a real forest landscape or urban
      area for 15 min. The systolic blood pressure, diastolic blood pressure, and pulse
      rate of each subject were measured. We analyzed the correlation between the
      initial values (after city viewing) and the differences in values between the two
      environments (after forest viewing-after city viewing). RESULTS: There was a
      negative correlation between the initial values and the differences in values
      between the two environments. The subjects whose initial systolic blood pressure,
      diastolic blood pressure, and pulse rate were high showed marked decreases in
      these parameters as their response after viewing the forest environment, whereas
      those whose initial systolic blood pressure, diastolic blood pressure, and pulse
      rate were low showed increases in these parameters as their response.
      CONCLUSIONS: These results support the premise that the physiological effect of a
      forest environment can differ depending on a subject's initial response values.
      Moreover, it was clear that forest therapy caused physiological adjustment,
      normalizing blood pressure and pulse rate.

PMID- 24858507
TI  - Possibility of clinical applications of forest medicine.
AB  - Since 2004, we have conducted a series of studies of the effect of forest therapy
      on human health and established forest therapy as a new preventive strategy. We
      have found that forest therapy has many beneficial effects on human health.
      However, there is almost no study dealing with the possibility of clinical
      applications of forest therapy. In this review, we discuss the possibility of
      clinical applications of forest therapy from the following viewpoints: 1. Forest
      therapy can decrease blood pressure, heart rate, sympathetic nerve activity, and
      levels of stress hormones, such as urinary adrenaline and noradrenaline, and can
      increase parasympathetic nerve activity, suggesting its preventive effect on
      hypertension. 2. Forest therapy can also decreace the scores for anxiety,
      depression, anger, fatigue, and confusion and increase the score for vigor in the
      Profile of Mood States (POMS) test, suggesting its preventive effect on mental
      depression. 3. Forest therapy can increase the activity and number of human
      natural killer (NK) cells and the intracellular levels of anticancer proteins,
      suggesting its preventive effect on cancers. 4. These findings suggest that
      forest therapy may have preventive effects on lifestyle-related diseases.
      However, the above preventive effects of forest therapy should be confirmed in
      clinical research.

PMID- 24858508
TI  - Forest medicine research in Japan.
AB  - There has been growing attention on the effects of forest on physiological
      relaxation and immune recovery, particularly in forest medicine research, from a
      perspective of preventive medicine. Japan is a world leader in the accumulation
      of scientific data on forest medicine research. In this review, we summarize the
      research that has been conducted in this area since 1992. We conducted field
      experiment, involving 420 subjects at 35 different forests throughout Japan.
      After sitting in natural surroundings, these subjects showed decrease in the
      following physiological parameters compared with those in an urban control group:
      12.4% decrease in the cortisol level, 7.0% decrease in sympathetic nervous
      activity, 1.4% decrease in systolic blood pressure, and 5.8% decrease in heart
      rate. This demonstrates that stressful states can be relieved by forest therapy.
      In addition, it should be noted that parasympathetic nervous activity was
      enhanced by 55.0%, indicating a relaxed state. The results of walking experiments
      provided similar results. Li et al. demonstrated that immune function was
      enhanced by forest therapy in middle-aged employees who volunteered to
      participate in these experiments. Natural killer cell activity, an indicator of
      immune function, was enhanced by 56% on the second day and returned to normal
      levels. A significant increase of 23% was maintained for 1 month even after
      returning to urban life, clearly illustrating the preventive benefits of forest
      therapy. In an indoor room experiment, we conducted tests with the following: 1)
      olfactory stimulation using wood smell, 2) tactile stimulation using wood, and 3)
      auditory stimulation using forest sounds. These indoor stimulations also
      decreased the blood pressure and pulse rate, and induced a physiological
      relaxation effect. We anticipate that forest medicine will play an increasingly
      important role in preventive medicine in the future.

PMID- 24858509
TI  - Molecular mechanisms underlying copper homeostasis in Mammalian cells.
AB  - Copper (Cu) is an essential metal for living organisms that utilize oxygen for
      respiration and is required as a cofactor of redox-regulating enzymes, such as
      superoxide dismutase, ceruloplasmin, lysyl oxidase, tyrosinase, and dopamine beta
      hydroxylase. However, the redox-active property of this metal may have toxic
      effects on cells due to the generation of harmful reactive oxygen species. Given
      these circumstances, it is said that cells have a dependable system for Cu
      homeostasis that efficiently distributes this essential metal to cuproenzymes,
      thereby preventing damage to proteins, nucleic acids, sugars, and lipids. In
      particular, influx, efflux, and intracellular distribution with maintenance of
      the oxidation state of Cu are strictly regulated. Several groups of Cu-regulating
      factors have been identified in mammalian cells, i.e., Cu transporters, Cu
      chaperones, Cu-binding proteins/peptides, and others. In this review, the
      features of the Cu-regulating factors are concisely examined in terms of
      molecular mechanisms underlying Cu homeostasis in cells.

PMID- 24858510
TI  - Effect of stone Spa bathing and hot-spring bathing on pulse wave velocity in
      healthy, late middle-aged females.
AB  - OBJECTIVES: The purpose of this study was to clarify the effect of stone spa
      bathing (Ganban-yoku) and hot-spring bathing on brachial-ankle pulse wave
      velocity (baPWV) in healthy, late middle-aged females. METHODS: The subjects were
      13 females (mean age, 47.3 years). The skin and tympanic temperatures, blood
      pressure, and baPWV were measured before and after stone spa bathing and hot
      spring bathing. For the stone spa bathing, the subjects lay down three times for
      approximately 10 min each time over warm stone beds. RESULTS: Although body
      weight showed no change after the hot-spring bathing, it significantly increased
      after the stone spa bathing. The increase was significantly related to the amount
      of water intake. The skin and tympanic temperatures increased to a smaller degree
      after the stone spa bathing than after the hot-spring bathing. The diastolic
      blood pressure decreased to a smaller degree after the stone spa bathing. BaPWV
      showed no significant change after bathing both in the stone spa and in the hot
      spring. The results of multiple regression analysis showed that the factors
      significantly related to the change in baPWV after the stone spa bathing were the
      changes in skin and tympanic temperatures and habit of smoking, and that after
      the hot-spring bathing was the change in skin temperature. CONCLUSIONS: The
      results suggest that, compared with the hot-spring bathing, stone spa bathing
      causes less strain on the body. The stone spa bathing and hot-spring bathing
      showed no marked effect on baPWV. However, there is a possibility that the stone
      spa bathing may be used as a load for investigating arterial stiffness.

PMID- 24858513
TI  - Green ergonomics: combining sustainability and ergonomics.
AB  - BACKGROUND: When discussing ergonomics, the term 'sustainability' usually refers
      to the preservation of the human workforce. OBJECTIVE: However, in 2010
      Gulfstream Aerospace Corporation made a conscious effort to combine ergonomics
      and environmental sustainability in order to increase employee engagement for
      both programs. METHODS: They introduced a companywide campaign called Green Ergo
      which is the idea of creating ergonomic solutions from scrap material found on
      site. This concept embraced the true meaning of 'green' and encouraged engineers
      and employees all across the company to design innovative green ergonomic
      solutions. RESULTS: The idea generated over 35 new ergo solutions, reduced waste
      production, and solved over 700 ergo problems for a fraction of the cost of newly
      purchased items. CONCLUSION: The demand for these items grew large enough that
      the company outsourced their manufacturing to a local non-profit. The Green Ergo
      campaign has changed the culture of the company and has increased the level of
      buy-in for both the ergonomics and sustainability programs.

PMID- 24858512
TI  - Hepatitis B virus replication is blocked by a 2-hydroxyisoquinoline-1,3(2H,4H)
      dione (HID) inhibitor of the viral ribonuclease H activity.
AB  - Nucleos(t)ide analog drugs profoundly suppress Hepatitis B virus (HBV)
      replication but rarely cure the infection, so therapy is usually life-long. The
      nucleos(t)ide analogs inhibit the viral DNA polymerase and often push HBV to the
      brink of extinction, so it may be possible to eradicate HBV by suppressing HBV
      replication further. The HBV ribonuclease H (RNaseH) is a logical new drug target
      because it is the second of only two viral enzymes essential for viral
      replication. We recently developed a low throughput screening pipeline for
      inhibitors of the HBV RNaseH and viral replication. Here, we screened a series of
      twenty-three nitrogen-based polyoxygenated heterocycles including sixteen 2
      hydroxyisoquinoline-1,3(2H,4H)-dione derivatives for anti-HBV RNaseH activity.
      Nine compounds inhibited the HBV RNaseH, but activity was marginal for eight of
      them. Compound #1 [2-hydroxyisoquinoline-1,3(2H,4H)-dione, HID] was the best hit
      with an IC50 of 28.1MUM and an EC50 of 4.2MUM. It preferentially suppressed
      accumulation of the viral plus-polarity DNA strand in replication inhibition
      assays, indicating that replication was blocked due to suppression of HBV RNaseH
      activity. It had a CC50 of 75MUM, yielding a therapeutic index of ~18. The EC50
      value was 7-fold lower than the IC50, possibly due to cellular retention or
      metabolism of the compound, or higher affinity for the full-length enzyme than
      the recombinant form used for screening. These data indicate that the 2
      hydroxyisoquinoline-1,3(2H,4H)-diones will have different structure-activity
      relationships for the HBV and HIV RNaseHs. Therefore, HID compounds may provide a
      foundation for development of more effective RNaseH inhibitors of HBV
      replication. 

PMID- 24858514
TI  - Association between perceived present working conditions and demands versus
      attitude to early retirement among construction workers.
AB  - BACKGROUND: Early retirement is an increasing problem in the construction
      industry. There is limited information about causes leading employees to leave
      working life early. We have compared construction workers present situation with
      their perception of future demands at work to avoid early retirement. METHODS:
      All 87 employees in a medium-sized Norwegian construction company participated in
      the study. All were men and answered questionnaires on health and pain, work
      ability, mechanical exposure, psychosocial conditions, and demands regarding
      future working conditions. RESULTS: Most workers showed good work ability,
      irrespective of age. Many reported high levels of mechanical exposure at work.
      The level of musculoskeletal pain was higher in the middle-aged (30-50 year old)
      age groups and seniors aged over 50 years than among the youngest workers less
      than 30 years of age. All workers reported that good health was important for
      continued working. Most workers stated that future work must not be too
      physically demanding. Many workers reported relatively low job satisfaction;
      consequently an interesting job was rated as important for continuing work. Good
      social conditions were a high priority. CONCLUSIONS: According to the examined
      construction workers, good health and reduced levels of mechanical exposure at
      work are essential to avoid early retirement.

PMID- 24858515
TI  - Chemical cleaning re-invented: clean, lean and green.
AB  - A project undertaken in the Central Cleaning Department of Janssen, a Johnson and
      Johnson pharmaceutical company, demonstrates how ergonomics, environmental and
      industrial hygiene risks and quality concerns can be tackled simultaneously. The
      way equipment was cleaned was re-designed by an in-house cross-functional team to
      ensure a 'clean, lean and green' process. Initiatives included a new layout of
      the area, and new work processes and equipment to facilitate cleaning and
      handling items. This resulted in significant improvements: all ergonomics high
      risk tasks were reduced to moderate or low risk; hearing protection was no longer
      required; respirator requirement reduced by 67%; solvent use reduced by 73%;
      productivity improved, with 55% fewer operator hours required; and quality
      improved 40-fold. The return on investment was estimated at 3.125 years based on
      an investment of over ?1.5 million (2008 prices). This win-win intervention
      allowed ergonomics, environmental, industrial hygiene, productivity and quality
      concerns all to be addressed. 

PMID- 24858516
TI  - Occupant comfort and health in green and conventional university buildings.
AB  - BACKGROUND: Green building standards are significantly impacting modern
      construction practices. The resulting structures are more energy efficient, but
      their impact on occupant health has not been widely studied. OBJECTIVE: To
      investigate a range of indoor environment and ergonomic issues in green
      buildings. METHODS: Retrospective post-occupancy evaluation survey of 319
      occupants in two Leadership in Energy and Environmental Design (LEED) certified
      buildings and one conventional building on a Canadian University campus. RESULTS:
      Results show that working in the LEED buildings was a generally positive
      experience for their health, performance, and satisfaction. However, the LEED
      buildings did not always receive the highest ratings for environmental conditions
      or for health and productivity. Respondents indicated a range of concerns with
      thermal conditions, office lighting, noise and their overall workstation designs
      and these were not always better in the green buildings. CONCLUSIONS: These
      results highlight the need for better integration of ergonomic design into green
      buildings and into the LEED rating system, and these implications are discussed.

PMID- 24858517
TI  - Building spatial layout that supports healthier behavior of office workers: a new
      performance mandate for sustainable buildings.
AB  - BACKGROUND: The pursuit of efficiency and the permeation of communication
      technologies in modern workplace have increased prolonged sitting and physical
      inactivity among the white-collar workforce. Physical inactivity is a major risk
      factor for developing various chronic diseases and obesity. OBJECTIVE: This study
      intends to understand the impact of physical environment on both voluntary and
      imperative physical activity levels in an office building, and to collect
      evidence for design suggestions to encourage office workers' activity level on a
      daily basis. This study examined how proximity from individual workstations to
      various shared service and amenity spaces in the workplace (e.g., meeting spaces,
      copy areas, kitchens, restrooms, elevators, and stairs) is associated with office
      workers' physical activity level (e.g., sedentary and non-sedentary behavior) and
      their environmental and job satisfaction. PARTICIPANTS AND METHODS: To
      objectively measure physical activity, twenty-six office workers, in a three
      story office building, wore accelerometers for three consecutive days at work.
      Environmental and job satisfaction of office workers was measured by a
      questionnaire. Proximity variables were measured using the floor plans of the
      subject building. CONCLUSIONS: Participants on average were sedentary for 80% of
      the time during the study. Proximity to several service and amenity areas was
      positively associated with step counts and job satisfaction.

PMID- 24858518
TI  - Achieving LEED credit for ergonomics: Laying the foundation.
AB  - Despite guidance from the United States Green Building Council (USGBC) on the
      requirements for earning a Leadership in Energy and Environmental Design (LEED)
      ergonomics credit in the Innovation in Design and Innovation in Operations
      category, few projects have received the credit. The University of California,
      Berkeley ergonomics program, Ergonomics@Work, has aligned the ergonomics strategy
      to those of the USGBC and LEED to achieve the ergonomics credit in several new
      buildings. This article describes the steps needed to obtain the credit and
      highlights the opportunities it creates to partner with the project team to
      promote ergonomics. As a profession it is up to ergonomists to create the road
      map that incorporates ergonomics into the green building design. 

PMID- 24858519
TI  - Greening the work force in Brazilian hotels: the role of environmental training.
AB  - BACKGROUND: Organizations are increasingly required to reduce their environmental
      impact through the adoption of environmental management, which requires the
      support of human resource practices. OBJECTIVE: The objective of this study is to
      determine whether human resource management practices, especially training, are
      supporting environmental management practices at four hotels located in Brazil.
      METHODS: This research is qualitative, based on the analysis of four hotels in
      Brazil. RESULTS: Based on the systematized empirical evidence collected from four
      hotels (Hotels A, B, C, and D), it can be concluded that: (1) human resource
      management is still not fully aligned with environmental objectives at the hotels
      studied; (2) only Hotel B has implemented environmental management practices and
      aligned with human resource management in a more developed manner, which may
      indicate that these two variables of analysis could have interrelations; (3)
      environmental training as a human resource management practice was verified in
      all hotels analyzed. CONCLUSIONS: The greening of human resources practices is
      not fully aligned with environmental objectives in the hotels studied. If these
      hotels really wish to "go green," environmental training will be necessary. Hotel
      stakeholders play a major role in implementing the greening of the hotel
      industry.

PMID- 24858520
TI  - Ergonomics as a missing part of sustainability.
AB  - In the last twenty years, terms such as sustainable development, environmental
      protection, and sustainable design have been widely exploited, often without
      justification. Does ergonomics have a legitimate need or right to use these terms
      and to be the part of the process to which they refer? This paper discusses the
      relationship between ergonomics and the concept of sustainable development and
      its three elements of sustainability (environmental, social and economic), as the
      steps ergonomists need to take to secure and strengthen the influence in
      sustainability topics. 

PMID- 24858521
TI  - Changes in productivity, psychological wellbeing and physical wellbeing from
      working in a 'green' building.
AB  - BACKGROUND: Based on improvements in indoor environmental quality claims are that
      'green' buildings are healthier and promote greater productivity than
      conventional buildings. However, the empirical evidence over the last decade has
      been inconclusive, usually with flawed study designs. OBJECTIVE: This study
      explored whether a 'green' building leads to a healthier, more productive work
      environment. METHODS: A one-year, longitudinal comparison of two groups of
      employees of a large commercial bank; a group that moved into a GreenStar
      accredited building and a group that stayed in a conventional building, was
      conducted. Measures of psychological wellbeing, physical wellbeing, productivity,
      and perceptions of the physical environment were taken before the move, six
      months later, and one year later. RESULTS: Results indicate that the 'green'
      building group had significantly increased self-reported productivity and
      physical wellbeing. The perceptions of the physical work environment indicate
      that respondents in the 'green' building group experienced significant air
      quality improvements (specifically, reduced stale air, better ventilation,
      improved air movement, reduced humidity, and conditions that were not too drafty)
      but perceived the lighting conditions as dimmer. CONCLUSION: Despite positive
      findings 'green' building rating tools require amendment to focus on those
      qualities that actually lead to improved wellbeing and productivity.

PMID- 24858523
TI  - A framework for the study of behavior.
AB  - Behavior is defined as the expression of the activity of the nervous system. The
      basic units of behavior are perceptual mechanisms, central mechanisms, and motor
      mechanisms. These units can be organized into more complex units called behavior
      systems such as hunger, sex, aggression, fear, etc. Perceptual and central
      mechanisms include cognitive mechanisms such as ideas, beliefs, memories,
      intentions, and cognitive modules. Behavior can be analyzed at genetic,
      physiological, whole organism, and population levels, and the concepts used to
      analyze behavior should be appropriate to each level. One can ask causal,
      structural, and functional questions about current behavior, ontogeny, and
      phylogeny. Causal and functional questions are independent of each other and
      should not be confused. There has been much confusion and disagreement about the
      relation between cause and function, and several examples are analyzed. This
      article is part of a Special Issue entitled: In Honor of Jerry Hogan.

PMID- 24858522
TI  - Stigma related to sex work among men who engage in transactional sex with men in
      Ho Chi Minh City, Vietnam.
AB  - OBJECTIVES: Male sex workers (MSW) in Vietnam face high levels of stigma related
      to sex work, which may be associated with depression and increased vulnerability
      to HIV. METHODS: In 2010, 300 MSW completed a behavioral and psychosocial survey.
      Multivariable models assessed factors associated with sex work-related stigma and
      the association between stigma and depression. RESULTS: Factors associated with
      increased stigma included having disclosed sexual orientation to healthcare
      workers (b 1.75, 95 % CI 0.69-2.80), meeting clients in the street/park (b 1.42,
      95 % CI 0.32-2.52), and having been forced to have sex without a condom (b 2.36,
      95 % CI 1.27-3.45). Factors associated with decreased stigma included meeting
      clients via the telephone or internet (b -1.26, 95 % CI -2.39 to -0.12) and
      receiving financial support from family or friends (b -1.31, 95 % CI -2.46 to 
      0.17). Stigma was significantly associated with increased odds of depression (AOR
      1.07, 95 % CI 1.01-1.15). CONCLUSIONS: Addressing stigma and depression in HIV
      prevention interventions is crucial for tailoring these programs to MSWs' needs,
      and may result in decreased HIV spread.

PMID- 24858524
TI  - Low bone mineral density in Friedreich ataxia.
AB  - Friedreich ataxia (FRDA) is the most common inherited neurodegenerative ataxia.
      Apart from predominant neurological features an involvement of the skeletal
      system in terms of scoliosis and foot deformities is frequent. Disease-related
      falls, mobility restrictions, and wheelchair-dependency in later disease stages
      might additionally compromise bone structure in FRDA. The aim of this pilot study
      was to systematically evaluate the bone status in a representative FRDA cohort.
      Twenty-eight FRDA patients became enrolled in this cross-sectional study.
      Neurological assessment, a questionnaire comprising the history of fractures and
      osteoporosis as well as osteodensitometric measurements complemented with general
      and bone-specific laboratory parameters were performed. The WHO Fracture Risk
      Assessment tool (FRAX(r)) was applied, calculating the 10-year risk of suffering
      an osteoporotic fracture. Six patients (21.4 %) presented with a bone mineral
      density below the expected range for age in at least one of the examined sites
      (femoral neck, lumbar spine, and forearm) irrespective of their gender.
      Corresponding Z scores were significantly lower compared to normative values for
      the femoral neck and lumbar spine. Vitamin D status was insufficient in 11 and
      deficient in 8 FRDA patients. There was a strong negative correlation between
      ataxia severity, GAA repeat expansion and bone density in the femoral neck of
      FRDA patients. This is the first report of an increased rate of low bone mineral
      density in FRDA. Given the increased risk of falls, this data rectifies routine
      bone mineral density measurements in FRDA which may help to initiate therapeutic
      interventions to prevent this condition. 

PMID- 24858525
TI  - Memory for flip-flopping: detection and recollection of political contradictions.
AB  - During political campaigns, candidates often change their positions on
      controversial issues. Does changing positions create confusion and impair memory
      for a politician's current position? In 3 experiments, two political candidates
      held positions on controversial issues in two debates. Across the debates, their
      positions were repeated, changed, or held only in the second debate (control).
      Relative to the control condition, recall of the most recent position on issues
      was enhanced when change was detected and recollected, whereas recall was
      impaired when change was not recollected. Furthermore, examining the errors
      revealed that subjects were more likely to intrude a Debate 1 response than to
      recall a blend of the two positions, and that recollecting change decreased
      Debate 1 intrusions. We argue that detecting change produces a recursive
      representation that embeds the original position in memory along with the more
      recent position. Recollecting change then enhances memory for the politician's
      positions and their order of occurrence by accessing the recursive trace. 

PMID- 24858526
TI  - Clinical outcome of advanced squamous cell carcinoma of the conjunctiva.
AB  - BACKGROUND: To evaluate the outcome of surgical management of advanced squamous
      cell carcinoma (SCC) of the conjunctiva (American Joint Committee Cancer
      classification >III) and the rate of recurrences after treatment during follow
      up. Second, to investigate the incidence of orbital exenteration during follow
      up. METHODS: Thirty-eight cases with SCC >grade T3 AJCC were retrospectively
      analysed at a University Eye Hospital Munich. Tumour stage, type of treatment,
      follow-up time, risk factors and--if present--recurrence were documented.
      RESULTS: The mean follow-up was 24.2 months (22.3-71 months). The most frequent
      surgical procedure was local tumour excision (n=25 patients, 71%). Orbital
      exenteration was performed in 10 patients (28%). Twenty patients (57%) did not
      show a progressive disease during follow-up. Of the patients with primary local
      excision, 13 (52%) had recurrence. Average time to recurrence for all treated
      patients was 24 months in the mean (minimum 4 months, maximum 68 months, SD, 22).
      Patients following orbital exenteration had recurrence of disease in 20% (n=2).
      None of the patients with primarily local tumour excision required an orbital
      exenteration. CONCLUSION: Advanced-stage SCC can be treated surgically. An
      extensive surgical approach is sometimes inevitable. Patients with surgical
      excision of advanced-stage disease should be reviewed closely as recurrences may
      occur and even after more than 5 years. However, on early detection, most of
      these recurrences can be handled by local excision.

PMID- 24858527
TI  - Maculopathy following extended usage of Clomiphene citrate.

PMID- 24858529
TI  - Eyelid nodule in a child: a chalazion or idiopathic facial aseptic granuloma?

PMID- 24858528
TI  - Fellow eye effect of unilateral intravitreal bevacizumab injection in eyes with
      diabetic macular edema.
AB  - AIMS: Anti-vascular endothelial growth factor compounds are routinely used for
      the treatment of diabetic macular edema (DME). We aim to evaluate for the
      existence and magnitude of treatment effect on fellow un-injected eyes. METHODS:
      A consecutive group of patients with bilateral DME who received unilateral
      bevacizumab injections was retrospectively evaluated. Data collected included
      demographics, ophthalmic and systemic findings, and optical coherence tomography
      (OCT) measurements of macular thickness. RESULTS: Thirty-five patients were
      evaluated. Mean follow-up was 245 days (range: 30-800), and the mean number of
      bevacizumab injections was 3.6 (range: 1-11). At end of follow-up, the mean (SD)
      OCT central subfield thickness reduced by 72 +/- 112 micron in the injected eye
      (from 469 +/- 139 to 397 +/- 120 micron; P=0.001), while in the non-injected eye
      it reduced by 49 +/- 75 micron (from 380 +/- 130 to 331 +/- 106 micron; P<0.001).
      Sixteen injected eyes (45.7%) showed central subfield thickness reduction of >=50
      micron while 10 (28.6%) non-injected eyes showed such thickness reduction.
      Improved VA following treatment was detected in 14 (40%) injected eyes and in 15
      (43%) non-injected eyes. CONCLUSIONS: Unilateral bevacizumab injections in
      patients with bilateral DME are often associated with bilateral response. SUMMARY
      STATEMENT: Anti-vascular endothelial growth factor compounds are routinely used
      for the treatment of diabetic macular edema (DME). In this retrospective study,
      we show that unilateral bevacizumab injections often result in reduction of the
      macular thickness in the fellow un-injected eye.

PMID- 24858530
TI  - Surgical management of corneal limbal dermoids: retrospective study of different
      techniques and use of Mitomycin C.
AB  - PURPOSE: We retrospectively studied the efficacy and safety of different surgical
      approaches to treating pediatric limbal dermoids with regard to intra and
      postoperative complications. METHODS: The data of 12 consecutive patients (14
      eyes), who underwent monocentric surgery of a limbal demoid in the past 9 years,
      were retrospectively analyzed for intra and postoperative complications. Group
      one consists of eleven eyes: seven eyes with a bare-sclera deep lamellar excision
      of the dermoid and four eyes with an additional amniotic membrane transplantation
      subsequent to excision. Group two consists of three eyes: two eyes treated with
      Mitomycin C 0.02% over 2 min following the excision, and one eye treated with
      Mitomycin C and amniotic membrane transplantation after removal of the dermoid.
      Follow-up ranged from 2 to 53 months (median 17 months). RESULTS: Intraoperative
      complications did not occur in any of the patients. Postoperatively, all patients
      showed corneal reepithelialization within a week. Limbal stem cell deficiency
      with a pseudopterygium developed in four eyes, one treated with bare-sclera
      excision and the others with amniotic membrane transplantation. One
      pseudopterygium had to be removed surgically because of visual acuity
      deterioration. Not a single eye treated with Mitomycin C developed a
      pseudopterygium. CONCLUSIONS: The transplantation of amniotic membrane following
      removal of a limbal dermoid cannot prevent the occurrence of a pseudopterygium.
      However, the use of Mitomycin C seems to have a protective effect.

PMID- 24858531
TI  - Glaucoma prescribing trends in England 2000 to 2012.
AB  - PURPOSE: In 2009, the National Institute for Clinical Excellence (NICE) published
      guidance on the treatment of ocular hypertension and glaucoma. The aim of the
      present study was to describe the impact this guidance had on glaucoma
      prescribing and to describe recent prescribing trends in England. METHOD:
      Prescribing cost analysis data held by NHS Business Authority for the years 2000
      2012 was analysed. RESULTS: The number of prescriptions dispensed increased by
      67% from 4.76 million in 2000 to 7.96 million in 2012. Over the same time period,
      drug costs increased by 88% from L55.2 million to L103.7 million. Prescriptions
      for prostaglandin analogues increased fourfold, while there was a threefold
      decrease in the use of beta-blockers. The most commonly prescribed glaucoma
      medication was latanoprost. The introduction of generic latanoprost in 2012 more
      than halved the cost associated with this medication. NICE guidance appeared to
      have had no effect on the total number of prescriptions or the classes of
      medications prescribed. CONCLUSION: The introduction of the NICE guidelines did
      not change glaucoma prescribing practice, although it is not clear whether this
      represents non-adherence to the guidelines or whether the guidelines embodied pre
      existing practice.

PMID- 24858533
TI  - The incomplete border sign.

PMID- 24858532
TI  - Comparative genome-wide transcriptional analysis of human left and right internal
      mammary arteries.
AB  - In coronary artery bypass grafting (CABG), the combined use of left and right
      internal mammary arteries (LIMA and RIMA) - collectively known as bilateral IMAs
      (BIMAs) provides a survival advantage over the use of LIMA alone. However, gene
      expression in RIMA has never been compared to that in LIMA. Here we report a
      genome-wide transcriptional analysis of BIMA to investigate the expression
      profiles of these conduits in patients undergoing CABG. As expected, in comparing
      the BIMAs to the aorta, we found differences in pathways and processes associated
      with atherosclerosis, inflammation, and cell signaling - pathways which provide
      biological support for the observation that BIMA grafts deliver long-term
      benefits to the patients and protect against continued atherosclerosis. These
      data support the widespread use of BIMAs as the preferred conduits in CABG. 

PMID- 24858534
TI  - Chronic pulmonary microaspiration: high-resolution computed tomographic findings
      in 13 patients.
AB  - PURPOSE: The aim of the study was to describe the high-resolution computed
      tomography (CT) manifestations of chronic pulmonary microaspiration, a condition
      characterized by recurrent subclinical aspiration of small droplets of gastric
      contents or foreign particles into the lungs. MATERIALS AND METHODS: We reviewed
      the CT findings in 13 consecutive patients with clinical (n=13) and histologic
      (n=1) diagnosis of chronic pulmonary microaspiration. Twelve patients presented
      with persistent cough, but none had a clinical history of acute aspiration. One
      patient was asymptomatic. All patients had volumetric CT of the chest
      reconstructed using thin sections (1 to 1.3 mm) at the time of diagnosis. The CT
      scans were interpreted by 3 chest radiologists who reached a final decision by
      consensus. RESULTS: All 13 patients had centrilobular nodules and ground-glass
      opacities that involved mainly the dependent lung regions in 11 patients and had
      a random distribution in 2. Other common findings included branching opacities
      (n=10), small foci of consolidation (n=7), septal lines (n=5), and bronchiectasis
      (n=7). The 13 patients had at least 1 risk factor for aspiration including
      gastroesophageal reflux (n=9), hiatus hernia (n=6), esophageal dysfunction (n=3),
      oropharyngeal dysphagia (n=1), esophageal carcinoma (n=1), and use of sedatives
      (n=2). CONCLUSIONS: The high-resolution CT manifestations of chronic pulmonary
      microaspiration consist mainly of centrilobular nodules and ground-glass
      opacities that tend to involve predominately the dependent regions. Branching
      opacities and small foci of consolidation are seen in the majority of cases.

PMID- 24858535
TI  - Lycium barbarum polysaccharide attenuates alcoholic cellular injury through TXNIP
      NLRP3 inflammasome pathway.
AB  - Lycium barbarum has been used as a traditional Chinese medicine to nourish liver,
      kidneys and the eyes. However, the underlying mechanisms of its hepatic
      protective properties remain uncertain. In this study, we aimed to investigate
      whether thioredoxin-interacting protein (TXNIP) and NOD-like receptor 3 (NLRP3)
      inflammasome mediated the attenuation of ethanol-induced hepatic injury by Lycium
      barbarum polysaccharide (LBP). Rat normal hepatocyte line BRL-3A was pre-treated
      with LBP prior to ethanol incubation. Hepatic damages, including apoptosis,
      inflammation, and oxidative stress, were measured. Then the inhibition of
      endogenous TXNIP expression was achieved by using its specific siRNA to test its
      possible involvement in the injury attenuation. We found that 50MUg/ml LBP pre
      treatment significantly alleviated 24-h ethanol exposure-induced overexpression
      of TXNIP, increased cellular apoptosis, secretion of inflammatory cytokines,
      activation of NLRP3 inflammasome, production of ROS, and reduced antioxidant
      enzyme expression. Silence of TXNIP suppressed the activated NLRP3 inflammasome,
      increased oxidative stress and worsened apoptosis in the cells. Further addition
      of LBP did not influence the effects of TXNIP inhibition on the cells. In
      conclusion, inhibition of hepatic TXNIP by LBP contributes to the reduction of
      cellular apoptosis, oxidative stress and NLRP3 inflammasome-mediated
      inflammation. 

PMID- 24858536
TI  - The predictive and prognostic value of the Glasgow Prognostic Score in metastatic
      colorectal carcinoma patients receiving bevacizumab.
AB  - The Glasgow Prognostic Score (GPS), based on C-reactive protein and albumin
      levels, has shown its prognostic value in metastatic colorectal carcinoma (mCRC)
      patients receiving conventional cytotoxic therapy. Bevacizumab, a monoclonal
      antibody to vascular epidermal growth factor, improves the overall survival in
      mCRC. The aim of the present study was to assess the prognostic value of GPS in
      mCRC patients receiving antivascular epidermal growth factor therapy. From August
      2005 to August 2012, consecutive patients with mCRC who received chemotherapy
      plus bevacizumab were eligible for the present analysis. The clinical stage, C
      reactive protein, albumin and the Eastern Cooperative Oncology Group performance
      status were recorded at the time of initiation of bevacizumab. Patients received
      5-fluorouracil-based chemotherapy plus bevacizumab in accordance with the
      digestive oncology multidisciplinary staff proposal and in line with the French
      recommendations for the treatment of mCRC. Eighty patients were eligible (colon n
      = 59, rectum n = 21), with a median follow-up of 14 months (range 1-58 months).
      Chemotherapy given with bevacizumab and 5-fluorouracil was oxaliplatin (n = 41,
      51%) or irinotecan (n = 27, 34%). At baseline, 56, 31 and 13% of patients had a
      GPS of 0 (n = 45), 1 (n = 25) and 2 (n = 10), respectively. The median
      progression-free survival in these groups was 10.1, 6.5 and 5.6 months (P =
      0.16), respectively. The median overall survival was 20.1, 11.4 and 6.5 months,
      respectively (P = 0.004). Our study confirmed the prognostic value of GPS in mCRC
      patients receiving chemotherapy plus bevacizumab. Given the poor survival
      observed in patients with an GPS of 2, studies dedicated to these patients could
      identify optimal treatment modalities.

PMID- 24858537
TI  - A simple method to engineer a protein-derived redox cofactor for catalysis.
AB  - The 6*-Histidine tag which is commonly used for purification of recombinant
      proteins was converted to a catalytic redox-active center by incorporation of
      Co(2+). Two examples of the biological activity of this engineered protein
      derived cofactor are presented. After inactivation of the natural diheme cofactor
      of MauG, it was shown that the Co(2+)-loaded 6*His-tag could substitute for the
      hemes in the H2O2-driven catalysis of tryptophan tryptophylquinone biosynthesis.
      To further demonstrate that the Co(2+)-loaded 6*His-tag could mediate long range
      electron transfer, it was shown that addition of H2O2 to the Co(2+)-loaded 6*His
      tagged Cu(1+) amicyanin oxidizes the copper site which is 20A away. These results
      provide proof of principle for this simple method by which to introduce a
      catalytic redox-active site into proteins for potential applications in research
      and biotechnology. 

PMID- 24858538
TI  - N450 as a candidate neural marker for interference control deficits in children
      with learning disabilities.
AB  - A deficit in the ability to suppress irrelevant or interfering stimuli may
      account for a variety of dysfunctional behaviors in children with learning
      disabilities (LD). However, neural correlates underlying this deficit in
      interference control in the LD are still unknown. In this study, we recruited a
      group of children with LD (age: 10.78 +/- 0.52) along with an age-matched control
      group (age: 10.74 +/- 0.86) and asked them to perform a numerical Stroop task.
      During the task, we used electroencephalogram (EEG) to record their event-related
      potentials (ERPs). We further evaluated performance of these children on a
      battery of tests, including the Academic Adaptability Test (AAT), an adapted
      Chinese version of Pupil Rating Scale (PRS), and Raven's Standard Progressive
      Matrices (SPM). Children's scores on recent math and Chinese exams were also
      obtained. Results showed that: 1) children with LD had worse performance in the
      incongruent condition of the numerical Stroop task suggesting that children with
      LD had interference control deficits but not basic numerical cognition; 2)
      children with LD had larger N450 effects on the frontal and posterior sites, but
      did not show any difference in early ERP components, suggesting that the
      behavioral difference was related with interference control rather than early
      visual perception processing; and 3) N450 effects were correlated with accuracy
      in the numerical Stroop task, performance in Raven's SPM, as well as school math
      performance. These results suggest that N450 can serve as a potential
      electrophysiology marker for identifying and potentially, providing targeted
      intervention for children with LD.

PMID- 24858539
TI  - Tetris is a foldback transposon that provided the building blocks for an emerging
      satellite DNA of Drosophila virilis.
AB  - Transposable elements (TEs) and satellite DNAs (satDNAs) are abundant components
      of most eukaryotic genomes studied so far and their impact on evolution has been
      the focus of several studies. A number of studies linked TEs with satDNAs, but
      the nature of their evolutionary relationships remains unclear. During in silico
      analyses of the Drosophila virilis assembled genome, we found a novel DNA
      transposon we named Tetris based on its modular structure and diversity of
      rearranged forms. We aimed to characterize Tetris and investigate its role in
      generating satDNAs. Data mining and sequence analysis showed that Tetris is
      apparently nonautonomous, with a structure similar to foldback elements, and
      present in D. virilis and D. americana. Herein, we show that Tetris shares the
      final portions of its terminal inverted repeats (TIRs) with DAIBAM, a previously
      described miniature inverted transposable element implicated in the generation of
      chromosome inversions. Both elements are likely to be mobilized by the same
      autonomous TE. Tetris TIRs contain approximately 220-bp internal tandem repeats
      that we have named TIR-220. We also found TIR-220 repeats making up longer (kb
      size) satDNA-like arrays. Using bioinformatic, phylogenetic and cytogenomic
      tools, we demonstrated that Tetris has contributed to shaping the genomes of D.
      virilis and D. americana, providing internal tandem repeats that served as
      building blocks for the amplification of satDNA arrays. The beta-heterochromatic
      genomic environment seemed to have favored such amplification. Our results imply
      for the first time a role for foldback elements in generating satDNAs. 

PMID- 24858540
TI  - Dibenzo[1,4,5]thiadiazepine: a hardly-known heterocyclic system with
      neuroprotective properties of potential usefulness in the treatment of
      neurodegenerative diseases.
AB  - In this work we describe a new family of dibenzo[1,4,5]thiadiazepines (2-12) that
      showed an interesting in vitro biological profile, namely neuroprotective and
      antioxidant properties, as well as blockade of cytosolic calcium entry. They
      showed no cytotoxic effects and the majority were predicted as CNS-permeable
      compounds. In human neuroblastoma cells they displayed good neuroprotective
      properties against mitochondrial oxidative stress which, in many cases, almost
      reached the full protection (>90%) when compounds were incubated with cells 24 h
      before the addition of toxic stressors. In co-incubation conditions these figures
      were smaller, although some compounds maintained an interesting level of
      neuroprotection, higher than 50%. Four selected compounds (2, 5, 8, and 11) were
      found to be effective antioxidant agents by sequestering mitochondrial radical
      oxygen species (ROS). Moreover, compound 2 showed a remarkable calcium-channel
      modulating activity. The interest of these compounds is increased by the fact
      that dibenzo[1,4,5]thiadiazepine is a barely known structure that is not
      difficult to synthesize and presents very few described derivatives, opening a
      new and broad line of research in Medicinal Chemistry. 

PMID- 24858541
TI  - Synthesis and biological evaluation of chalcones as potential antileishmanial
      agents.
AB  - Antileishmanial activities of thirty-five synthetic chalcones have been examined.
      Among them, ten compounds (4, 6, 16, 22, 23, 24, 25, 29, 35 and 37) exhibited
      potent in vitro activity (IC50 range from 1.70 to 8 MUM) against extracellular
      promastigotes and intracellular amastigotes form of Leishmania donovani. Two
      promising compounds 22 and 37 were tested in vivo in L. donovani/hamster model.
      Chalcone 37 showed 83.32% parasite inhibition at a dose of 50 mg/kg for 10 days
      whereas, 75.89% parasite inhibition at 100 mg/kg dose for 5 days by
      intraperitoneal route at day 7 post-treatment. 

PMID- 24858542
TI  - Regioselective synthesis of polycyclic aza-oxa and aza-oxa-thia heteroarenes as
      Colo-205 and HepG2 carcinoma cells growth inhibitors.
AB  - An efficient regioselective synthesis of polycyclic diheteroaryl[b,d]pyrans and
      diheteroaryl[c,e][1,2]diazepines has been reported through ring transformation
      reactions of 2-oxo-2,5-dihydrothiochromeno[4,3-b]pyrans (3,4), 2-oxo-5,6-dihydro
      2H-benzo[b]pyrano[2,3-d]oxepine/thiepine (8, 9) and 6-oxo-3,6-dihydro-2H
      naphtho[1,2-b]pyrano[2,3-d]oxepine (15) by hydrazine, at ambient and reflux
      temperature. Nine compounds viz 5a,b; 10a,c,d; 12b; 13b; 16 and 1-methylthio-5,6
      dihydrobenzo[f]quinoline (0.1-100 MUM) were screened for their cytotoxicity in
      normal (IEC-6), carcinoma (Colo-205) and HepG2 cell lines. None of the compounds
      showed cytotoxicity in normal IEC-6 cells while 10a,d and 16 resulted in killing
      of Colo-205 cells with IC50 ranging 20-60 MUM while 10c and 13b caused killing of
      HepG2 cells with IC50 values ranging 60-80 MUM concentration. Further, 10a,d and
      16 caused apoptosis through a cascade of mitochondrial pathway in Colo-205 cells
      indicating anticancerous potential against intestinal cancer. Interestingly,
      compounds 10c and 13b exhibited apoptosis through mitochondrial pathway in HepG2
      cells suggesting anticancer activity against hepatic cancer. 

PMID- 24858543
TI  - Design, synthesis and biological evaluation of novel 4-alkapolyenylpyrrolo[1,2
      a]quinoxalines as antileishmanial agents--part III.
AB  - A series of new 4-alkapolyenylpyrrolo[1,2-a]quinoxaline derivatives, original and
      structural analogues of alkaloid chimanine B and of previously described 4
      alkenylpyrrolo[1,2-a]quinoxalines, was synthesized in good yields using efficient
      palladium-catalyzed Suzuki-Miyaura cross-coupling reactions. These new compounds
      were tested for in vitro antiparasitic activity upon three Leishmania spp.
      strains. Biological results showed activity against the promastigote forms of L.
      major, L. mexicana and L. donovani with IC50 ranging from 1.2 to 14.7 MUM. In
      attempting to investigate if our pyrrolo[1,2-a]quinoxaline derivatives are broad
      spectrum antiprotozoal compounds activities toward one Trypanosoma brucei brucei
      strain and the W2 and 3D7 Plasmodium falciparum strains were also investigated.
      In parallel, the in vitro cytotoxicity of these molecules was assessed on the
      murine J774 and human HepG2 cell lines. Structure-activity relationships of these
      new synthetic compounds are here discussed. 

PMID- 24858545
TI  - Recent developments of metal N-heterocyclic carbenes as anticancer agents.
AB  - Metal based anticancer drugs have demonstrated their crucial role in preventing
      all types of cancers whereas their effectiveness is selective with respect to the
      cancer cells rather than the normal cells. Recently metal N-heterocyclic carbenes
      have established their selective performance for cancer cells excluding normal
      healthy cells based on which they are widely utilised for targeting cancer cells
      specifically which leads to cell death or cell growth inhibition. This is mainly
      due to their ionic character which helps them to localise in cancer cells with
      the help of enhanced expression of Organic Cation Transporters (OCT). Also their
      unique mechanism of action involving DNA binding, less recognizable by DNA repair
      machinery, mitochondria targeting gives them a new area for anticancer drug
      development. This review summarises the medicinal as well as pharmacological
      approach to the anticancer properties of metal NHC complexes. 

PMID- 24858544
TI  - Design, synthesis and biological evaluation of arylcinnamide hybrid derivatives
      as novel anticancer agents.
AB  - The combination of two pharmacophores into a single molecule represents one of
      the methods that can be adopted for the synthesis of new anticancer molecules. A
      series of novel antiproliferative agents designed by a pharmacophore
      hybridization approach, combining the arylcinnamide skeleton and an alpha
      bromoacryloyl moiety, was synthesized and evaluated for its antiproliferative
      activity against a panel of seven human cancer cell lines. In addition, the new
      derivatives were also active on multidrug-resistant cell lines over-expressing P
      glycoprotein. The biological effects of various substituents on the N-phenyl ring
      of the benzamide portion were also described. In order to study the possible
      mechanism of action, we observed that 4p slightly increased the Reactive Oxygen
      Species (ROS) production in HeLa cells, but, more importantly, a remarkable
      decrease of intracellular reduced glutathione content was detected in treated
      cells compared with controls. These results were confirmed by the observation
      that only thiol-containing antioxidants were able to significantly protect the
      cells from induced cell death. Altogether our results indicate that the new
      derivatives are endowed with good anticancer activity in vitro, and their
      properties may result in the development of new cancer therapeutic strategies. 

PMID- 24858546
TI  - Guanidinium-based derivatives: searching for new kinase inhibitors.
AB  - Considering the structural similarities between the kinase inhibitor sorafenib
      and 4,4'-bis-guanidinium derivatives previously prepared by Rozas and co., which
      display interesting cytotoxicity in cancer cells, we have studied whether this
      activity could result from kinase inhibition. Five new families have been
      prepared consisting of unsubstituted and aryl-substituted 3,4'-bis-guanidiniums,
      3,4'-bis-2-aminoimidazolinium and 3-acetamide-4'-(4-chloro-3
      trifluoromethylphenyl)guanidinium derivatives. Cytotoxicity (measuring the IC50
      values) and apoptosis studies in human HL-60 promyelocytic leukemia cells were
      carried out for these compounds. Additionally, their potential inhibitory effect
      was explored on a panel of kinases known to be involved in apoptotic pathways.
      The previously prepared cytotoxic 4,4'-bis-guanidiniums did not inhibit any of
      these kinases; however, some of the novel 3,4'-substituted derivatives showed a
      high percentage inhibition of RAF-1/MEK-1, for which the potential mode of
      binding was evaluated by docking studies. The interesting antitumour properties
      showed by these compounds open up new exciting lines of investigation for kinase
      inhibitors as anticancer agents and also highlights the relevance of the
      guanidinium moiety for protein kinase inhibitors chemical design. 

PMID- 24858547
TI  - Recombinant adeno-associated virus: efficient transduction of the rat VMH and
      clearance from blood.
AB  - To promote the efficient and safe application of adeno-associated virus (AAV)
      vectors as a gene transfer tool in the central nervous system (CNS), transduction
      efficiency and clearance were studied for serotypes commonly used to transfect
      distinct areas of the brain. As AAV2 was shown to transduce only small volumes in
      several brain regions, this study compares the transduction efficiency of three
      AAV pseudotyped vectors, namely AAV2/1, AAV2/5 and AAV2/8, in the ventromedial
      nucleus of the hypothalamus (VMH). No difference was found between AAV2/1 and
      AAV2/5 in transduction efficiency. Both AAV2/1 and AAV2/5 achieved a higher
      transduction rate than AAV2/8. One hour after virus administration to the brain,
      no viral particles could be traced in blood, indicating that no or negligible
      numbers of virions crossed the blood-brain barrier. In order to investigate
      survival of AAV in blood, clearance was determined following systemic AAV
      administration. The half-life of AAV2/1, AAV2/2, AAV2/5 and AAV2/8 was calculated
      by determining virus clearance rates from blood after systemic injection. The
      half-life of AAV2/2 was 4.2 minutes, which was significantly lower than the half
      lives of AAV2/1, AAV2/5 and AAV2/8. With a half-life of more than 11 hours,
      AAV2/8 particles remained detectable in blood significantly longer than AAV2/5.
      We conclude that application of AAV in the CNS is relatively safe as no AAV
      particles are detectable in blood after injection into the brain. With a half
      life of 1.67 hours of AAV2/5, a systemic injection with 1*109 genomic copies of
      AAV would be fully cleared from blood after 2 days. 

PMID- 24858549
TI  - The interactions between pain, pain-related fear of movement and productivity.
AB  - BACKGROUND: Employees with physically heavy work have an increased risk of
      musculoskeletal disorders leading to reduced work ability. AIMS: To investigate
      if a high level of musculoskeletal pain or pain-related fear of movement was
      associated with low productivity among employees with physically heavy work and
      differing work ability levels. METHODS: The study was conducted at a Danish
      production site and employees with physically heavy work in the production line
      were included in the study. Work ability was assessed with the Work Ability Index
      (WAI), pain-related fear of movement with the Tampa Scale for Kinesiophobia and
      productivity and musculoskeletal pain by self-reported measures. Sickness absence
      records for construction of WAI were obtained from the workplace. RESULTS: There
      was a 77% response rate with 350 employees included in the final analysis. Among
      employees with only moderate work ability, there was neither an association
      between pain and productivity nor between pain-related fear of movement and
      productivity. For employees with good work ability, higher levels of pain and
      higher levels of pain-related fear of movement both raised the odds of low
      productivity significantly. CONCLUSIONS: Despite the fact that musculoskeletal
      pain increases the risk of reduced work ability significantly, musculoskeletal
      pain and pain-related fear of movement were associated with low productivity only
      among employees with good work ability.

PMID- 24858548
TI  - CXC chemokine CXCL12 and its receptor CXCR4 in tree shrews (Tupaia belangeri):
      structure, expression and function.
AB  - Chemokines are small secreted proteins functionally involved in the immune
      system's regulation of lymphocyte migration across numerous mammalian species.
      Given its growing popularity in immunological models, we investigated the
      structure and function of chemokine CXCL12 protein in tree shrews. We found that
      CXCL12 and its receptor CXCR4 in tree shrew had structural similarities to their
      homologous human proteins. Phylogenetic analysis supports the view that tree
      shrew is evolutionarily-close to the primates. Our results also showed that the
      human recombinant CXCL12 protein directly enhanced the migration of tree shrew's
      lymphocytes in vitro, while AMD3100 enhanced the mobilization of hematopoietic
      progenitor cells (HPCs) from bone marrow into peripheral blood in tree shrew in
      vivo. Collectively, these findings suggested that chemokines in tree shrews may
      play the same or similar roles as those in humans, and that the tree shrew is a
      viable animal model for studying human immunological diseases. 

PMID- 24858550
TI  - Wayfinding difficulties among elders with dementia in an assisted living
      residence.
AB  - The concerning phenomena of spatial disorientation and wayfinding difficulties
      among elders with Alzheimer's disease or a related dementia in assisted living
      residences are understudied. This qualitative study aimed to identify the types
      of wayfinding difficulties as experienced by residents with memory-loss in two
      special care units of an assisted living residence. The data collection period
      included participant observation complemented by semi-structured interviews with
      care staff and managers and review of clinical records. A wide spectrum of
      wayfinding difficulties was identified as experienced by six residents. The
      residents experienced difficulties reaching several destinations on the units.
      The implications of the findings to practice, architectural design, and policy
      are discussed. 

PMID- 24858551
TI  - Core principles for involving people with dementia in research: innovative
      practice.
AB  - The Scottish Dementia Working Group Research Sub-group is part of the Scottish
      Dementia Working Group, an internationally renowned campaigning group of people
      with dementia. We co-created our core principles for involving people with
      dementia in research between September and December 2013. The principles address
      six areas: (i) how people with dementia are valued and involved in research, (ii)
      lived experience as valid knowledge, (iii) physical and emotional safety, (iv)
      accessibility of all aspects of research, (v) training for researchers and (vi)
      the impact of our experiences of time on research processes. Through our core
      principles, we challenge researchers across all disciplines to re-consider how we
      and other people with dementia are involved in research as well as how knowledge
      in dementia research is created. 

PMID- 24858552
TI  - Ethnic minority, young onset, rare dementia type, depression: A case study of a
      Muslim male accessing UK dementia health and social care services.
AB  - A case study comprised of formal interviews, formal observations and informal
      discussions investigated the motivations and experiences accessing dementia care
      health and social care services for a Muslim, Pakistani male with dementia.
      Motivations derived from 'desperation' and an inability to access support from
      family or religious community. Experiences of accessing services were mostly
      negative. Dementia services were ill-informed about how to support persons with
      young onset dementia, with pre-existing mental health conditions, from an ethnic
      minority. Education and training to remove barriers to all dementia care services
      is required for persons with dementia, their families and within dementia
      services and religious communities. 

PMID- 24858553
TI  - What do we know about the attitudes, experiences and needs of Black and minority
      ethnic carers of people with dementia in the United Kingdom? A systematic review
      of empirical research findings.
AB  - This paper reviews recent literature on the experiences, attitudes and needs of
      caring for someone with dementia in Black and minority ethnic communities in the
      United Kingdom. Eight articles, which investigated carer experiences from Black
      and minority ethnic communities when caring for someone with dementia, were
      critically appraised. All eight studies used a qualitative methodology. The
      review identified several themes and issues across the qualitative studies. These
      included memory loss being viewed as a normal process of ageing, care being
      perceived as an extension of an existing responsibility, a poor understanding of
      what support services provide, the influence of migration, the impact of stigma
      and increased female responsibility. Methodological limitations of the research
      literature studies are also highlighted and clinically relevant implications are
      discussed, alongside recommendations for future research in this area. 

PMID- 24858554
TI  - Chemical composition and morphology of renal stones.
AB  - Two issues related to nephrolithiasis are explored: (1) does the chemical
      composition and morphology of renal calculi in South Poland overlap with the
      studies from other countries? and (2) are there possibilities to evaluate in vivo
      chemical composition of stones using computed tomography? The study was conducted
      on 108 renal stones. X-ray fluorescence, X-ray diffraction and Fourier
      transformed infrared spectroscopy were used to determine the chemical
      composition. The morphology of the stones was examined using micro computed
      tomography. The stone chemical composition in South Poland indicate that calcium
      oxalate monohydrate was overwhelmingly dominant (84%) followed by hydroxyapatite
      (8%) and struvite (6%). The occurrence of uric acid stones was very low (2%). The
      relative frequency of various stone types is similar in South Poland to other
      industrialized countries. The studied renal stones were characterized by a large
      variability in the concentrations of both major and trace elements. The
      maximum/minimum concentration ratio exceeds two orders of magnitude. Significant
      morphological differences have been observed between different types of stones.
      The stones were composed of oxalate polyhedrons stuck together or had the
      phosphate core overlaid with layers oxalate and organic mater. The use of CT to
      identify stone type seems to be limited. 

PMID- 24858555
TI  - Negative emotional states of patients with oncological disease and social
      support.
AB  - For many people diagnosed cancer and the treatment process is connected with
      emergen- ce and long-term existence of many negative emotions such as:
      depression, anxiety and stress. The aim of this study was to evaluate the
      intensity of negative emotional states of people diagnosed with cancer and the
      need for social support, as well as, exploration of the interdependence between
      these variables. Statistical analysis showed a significant correlation between
      the occurrence of disorders and border states, of both anxiety and depressive
      character and high level of stress in the test. 

PMID- 24858556
TI  - Trans-foramen magnum examination of the sella turcica region in the macerated
      human skulls.
AB  - This report presents a method of quick and accurate imaging of the sellar region
      by means of the laryngological mirror equipped with a light pipe and followed by
      taking digital photograph as the mirror image visible through the foramen magnum.
      A technique of the intracranial imaging of the osseous structures was tested on
      the macerated human skulls. Images of the sellar region were presented as the
      example of quality of the employed technique, which can be regarded as a
      simplified version of the endoscopic examination. 

PMID- 24858557
TI  - Nerve supply of pelvic viscera - anatomical notes, clinical implication on nerve
      stimulation.
AB  - AIM: The aim of this study was to present review on pelvic plexuses in males and
      females with some referrals to clinical practice, specially to the methods
      including nerve stimulation. CONCLUSIONS: Anatomy of pelvic plexuses is still
      confusing. Much attention should be paid to further studies on the arrangement of
      pelvic plexuses specially because of nerve stimulation techniques.

PMID- 24858558
TI  - Stevia, cyclamate and saccharin - natural and artificial sweeteners - exert no
      effect on sulfane levels in tissues.
AB  - The interactions among natural and artificial sweeteners and endogenous sulfur
      metabolism have never been investigated. CBA strain mice were administered orally
      stevia, cyclamate or saccharin in doses of 5 mg/kg of body weight in water
      solutions each. The measurements of the free and acid-labile sulfane (H2S) tissue
      concentrations in brain, heart, liver and kidney were performed with Siegel
      spectrophotometric modified method. No differences in comparisons between
      hydrogen sulfide concentrations in the control group and each sweetener group
      within every tissue type were noted. In conclusion, stevia, cyclamate and
      saccharine do not change the endogenous sulfur metabolism to the extent of
      causing sulfane tissue levels alterations. 

PMID- 24858559
TI  - Morphology of a 19th century adult male skull with non-treated hydrocephalus - a
      case report.
AB  - This report presents the craniofacial morphology of a skull afflicted with
      hydrocephalus, belonging to an adult male who lived in the 19th century in
      Vienna. The volume of the skull (2022 cm3) exceeds normal capacity of a male
      skull which is estimated to be 1500 cm3. Diameters of the neurocranium and head
      circumference of the specimen differ significantly from normative values, while
      the facial diameters remain in normal range of variation. Characteristic features
      of the investigated skull are numerous accessory bones and sutures of the
      neurocranium. Overall the morphology of the cranial bones suggests that the male
      suffered from congenital hydrocephalus. 

PMID- 24858560
TI  - Angioarchitecture of uterine cervical leiomyomata - a SEM study.
AB  - AIM: he main goal of this study was assessment of vascular structure of cervical
      uterine leiomyomata. MATERIALS AND METHODS: The study was carried out on ten
      human uteri collected upon autopsy. Vessels were injected with synthetic resin,
      next corroded and coated with gold, finally observed using scanning electron
      microscope. RESULTS: Most of cervical fibroids were observed in the middle third
      of the wall of cervix. They were surrounded by relatively dense 'vascular
      capsule'. consisted of flattened vein, arterioles and capillaries. CONCLUSIONS:
      Structure of cervical uterine leiomyomata was similar to those observed in
      initial stage of growth of myometrial fibroids.

PMID- 24858561
TI  - Elevated interleukin-1beta serum level after chronic peripheral salsolinol
      administration.
AB  - The catechol isoquinoline derivatives are endogenous compounds present in the
      mammalian brain and the representative one is referred to as salsolinol. It may
      be formed from aromatic amines leading to neurotoxic N
      methyltetrahydroquinolinium ions that may play a role in the etiology of
      Parkinson's disease (PD). Neuroinflammation and apoptosis is thought to be a
      major contributor to the neuronal degeneration in PD. The alteration of
      inflammatory cytokines in the brain, cerebral spinal fluid and plasma of PD
      patients supports the existence of functional interconnections between the immune
      and nervous systems. In animal studies, chronic administration of salsolinol
      induced parkinsonian-like symptoms, both peripherally and centrally. However,
      still little has been known about the effects of salsolinol on the pro
      inflammatory cytokine production or mast cells activation in the gastrointestinal
      tract. Male Wistar rats were subjected to continuous intraperitoneal dosing of
      salsolinol (200 mg/kg in total) with osmotic mini-pumps for two or four weeks and
      fed with either standard or high fat diet. An equivalent group of rats served as
      the appropriate controls. At the end of the experiment animals were decapitated
      and blood samples as well as tissue fragments were collected. Serum samples were
      assayed immunoenzymatically for IL-11beta and by liquid chromatography-mass
      spectrometry for histamine. Tissue fragments from gastric antrum, duodenum and
      proximal colon were formalin fixed, paraffin-embedded and stained with either
      hematoxylin and eosin or toluidine blue. Once activated, mast cells might secrete
      a range of neurosensitizing and pro-inflammatory molecules, increasing gut-blood
      and blood-brain barrier permeability. Cytokines mediate the activity of immune
      cells and may affect brain neurochemistry. The results of the present work serve
      as an additional support for the existence of an interrelationship between the
      nervous and immune system. 

PMID- 24858562
TI  - Temporal variations in the abundance and composition of biofilm communities
      colonizing drinking water distribution pipes.
AB  - Pipes that transport drinking water through municipal drinking water distribution
      systems (DWDS) are challenging habitats for microorganisms. Distribution networks
      are dark, oligotrophic and contain disinfectants; yet microbes frequently form
      biofilms attached to interior surfaces of DWDS pipes. Relatively little is known
      about the species composition and ecology of these biofilms due to challenges
      associated with sample acquisition from actual DWDS. We report the analysis of
      biofilms from five pipe samples collected from the same region of a DWDS in
      Florida, USA, over an 18 month period between February 2011 and August 2012. The
      bacterial abundance and composition of biofilm communities within the pipes were
      analyzed by heterotrophic plate counts and tag pyrosequencing of 16S rRNA genes,
      respectively. Bacterial numbers varied significantly based on sampling date and
      were positively correlated with water temperature and the concentration of
      nitrate. However, there was no significant relationship between the concentration
      of disinfectant in the drinking water (monochloramine) and the abundance of
      bacteria within the biofilms. Pyrosequencing analysis identified a total of 677
      operational taxonomic units (OTUs) (3% distance) within the biofilms but
      indicated that community diversity was low and varied between sampling dates.
      Biofilms were dominated by a few taxa, specifically Methylomonas, Acinetobacter,
      Mycobacterium, and Xanthomonadaceae, and the dominant taxa within the biofilms
      varied dramatically between sampling times. The drinking water characteristics
      most strongly correlated with bacterial community composition were concentrations
      of nitrate, ammonium, total chlorine and monochloramine, as well as alkalinity
      and hardness. Biofilms from the sampling date with the highest nitrate
      concentration were the most abundant and diverse and were dominated by
      Acinetobacter. 

PMID- 24858564
TI  - Is there a relationship between endometrial polyps and obesity, diabetes
      mellitus, hypertension?
AB  - OBJECTIVE: The purpose of our study was to evaluate the relationship between
      endometrial polyps and obesity, diabetes mellitus (DM) and hypertension (HT).
      MATERIALS AND METHODS: 202 patients who applied to our gynecology clinic with
      complaints of infertility, recurrent pregnancy loss and abnormal uterine
      bleeding, diagnosed to have endometrial polyps by hysteroscopy, were compared
      with 79 patients without polyps, retrospectively. The relationships between risk
      factors and presence of a polyp and polyp size were analyzed. RESULTS: The mean
      age of cases with endometrial polyps was significantly greater than the controls.
      The mean body mass index (BMI) of the cases with polyps was also significantly
      greater than the controls. There was no significant difference between groups
      with respect to prevalence of DM or HT. CONCLUSION: This study suggests that
      obesity is an independent risk factor in the development of endometrial polyps.
      Clinicians should be aware in terms of endometrial polyps in the assessment of
      patients with BMI >=30. There was no relationship between HT or DM with presence
      of polyps.

PMID- 24858563
TI  - CCHCR1 interacts with EDC4, suggesting its localization in P-bodies.
AB  - Coiled-coil alpha-helical rod protein 1 (CCHCR1) is suggested as a candidate
      biomarker for psoriasis for more than a decade but its function remains poorly
      understood because of the inconsistent findings in the literature. CCHCR1 protein
      is suggested to be localized in the cytoplasm, nucleus, mitochondria, or
      centrosome and to regulate various cellular functions, including steroidogenesis,
      proliferation, differentiation, and cytoskeleton organization. In this study, we
      attempted to find a consensus between these findings by identifying the
      interaction partners of CCHCR1 using co-immunoprecipiation with a stable cell
      line expressing EGFP-tagged CCHCR1. Out of more than 100 co-immunoprecipitants
      identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS), the
      enhancer of mRNA-decapping protein 4 (EDC4), which is a processing body (P-body)
      component, was particularly found to be the major interacting partner of CCHCR1.
      Confocal imaging confirmed the localization of CCHCR1 in P-bodies and its N
      terminus is required for this subcellular localization, suggesting that CCHCR1 is
      a novel P-body component. As P-bodies are the site for mRNA metabolism, our
      findings provide a molecular basis for the function of CCHCR1, any disruption of
      which may affect the transcriptome of the cell, and causing abnormal cell
      functions. 

PMID- 24858565
TI  - Answer to: letter to the editor entitled "hysteroscopic metroplasty: reproductive
      outcome in relation to septum size".

PMID- 24858566
TI  - Safety and immunogenicity in man of a cell culture derived trivalent live
      attenuated seasonal influenza vaccine: a Phase I dose escalating study in healthy
      volunteers.
AB  - Live attenuated influenza vaccine (LAIV) offers the promise of inducing a variety
      of immune responses thereby conferring protection to circulating field strains.
      LAIVs are based on cold adapted and temperature sensitive phenotypes of master
      donor viruses (MDVs) containing the surface glycoprotein genes of seasonal
      influenza strains. Two types of MDV lineages have been described, the Ann Arbor
      lineages and the A/Leningrad/17 and B/USSR/60 lineages. Here the safety and
      immunogenicity of a Madin Darby Canine Kidney - cell culture based, intranasal
      LAIV derived from A/Leningrad/17 and B/USSR, was evaluated in healthy influenza
      non-naive volunteers 18-50 years of age. In a double-blind, randomized, placebo
      controlled design, single escalating doses of 1*10(5), 1*10(6), or 1*10(7) tissue
      culture infectious dose 50% (TCID50) of vaccine containing each of the three
      influenza virus re-assortants recommended by the World Health Organization for
      the 2008-2009 season were administered intranasally. A statistically significant
      geometric mean increase in hemagglutination inhibition titer was reached for
      influenza strain A/H3N2 after immunization with all doses of LAIV. For the A/H1N1
      and B strains, the GMI in HI titer did not increase for any of the doses. Virus
      neutralization antibody titers showed a similar response pattern. A dose-response
      effect could not be demonstrated for any of the strains, neither for the HI
      antibody nor for the VN antibody responses. No influenza like symptoms, no nasal
      congestions, no rhinorrhea, or other influenza related upper respiratory tract
      symptoms were observed. In addition, no difference in the incidence or nature of
      adverse events was found between vaccine and placebo treated subjects. Overall,
      the results indicated that the LAIV for nasal administration is immunogenic (i.e.
      able to provoke an immune response) and safe both from the perspective of the
      attenuated virus and the MDCK cell line from which it was derived, and it
      warrants further development. 

PMID- 24858567
TI  - Overexpression of goosecoid homeobox is associated with chemoresistance and poor
      prognosis in ovarian carcinoma.
AB  - Ovarian carcinoma is the most lethal cancer among all gynecological malignancies
      due to recurrence through chemoresistance. The aim of the present study was to
      identify new biomarkers to predict chemoresistance and prognosis in ovarian
      carcinomas. The mRNA expression by qRT-PCR was examined in 60 ovarian serous
      carcinomas for selected genes from the screening by PCR array focusing on
      apoptosis, epithelial-to-mesenchymal transition and cancer pathways. The clinical
      impact was assessed by analyzing the correlation between gene expression and
      clinicopathological variables. Further validation with immunohistochemistry was
      performed with 75 cases of serous carcinomas. The chemoresistance was
      significantly associated with high expression of FOS, GSC, SNAI1, TERT and
      TNFRSF10D, and low expression of CDKN1A, TNFRSF10A, TNFRSF10C and TRAF1 (p<0.05,
      t-test). Low expression of TRAF1 and high expression of E2F1, FOS, TERT and GSC
      were significantly associated with advanced clinical stage (p<0.05, chi2-test).
      Lymph node metastasis was significantly associated with high expression of GSC.
      The upregulation group of TERT, GSC, NOTCH1 and SNAI1, and downregulation group
      of TRAF1 were significantly associated with poor overall survival (p<0.05, log
      rank test). On further validation with immunohistochemistry, overexpression of
      goosecoid homeobox (GSC) was associated with poor overall survival. The results
      suggest that GSC is the most potential biomarker of drug response and poor
      prognosis in ovarian serous carcinomas.

PMID- 24858568
TI  - Balloon brachytherapy for breast cancer prove that it works? Or, prove that it
      doesn't?
AB  - Balloon breast brachytherapy is a catheter-based technique to deliver high local
      concentration of radiation following breast-sparing surgery. Although this
      technique is logically appealing--providing more directed radiation to sites at
      high risk of local failure--there remains little empirical support that this
      intervention is non-inferior to external beam radiotherapy, a well-established
      standard. Additionally, observational studies suggest that balloon brachytherapy
      is associated with high rates of local complications, and higher rates of
      subsequent mastectomy, a marker of local failure. Here, I explore regulatory and
      clinical considerations that lead to the widespread adoption of breast
      brachytherapy. I argue that the therapy spread before its efficacy was confirmed.
      Breast brachytherapy illustrates ongoing complexities in the approval of novel
      devices.

PMID- 24858569
TI  - Serum alkaline phosphatase differentiates prostate-specific antigen flare from
      early disease progression after docetaxel chemotherapy in castration-resistant
      prostate cancer with bone metastasis.
AB  - PURPOSE: A transient rise in prostate-specific antigen (PSA) after the initiation
      of chemotherapy, called as PSA flare, has been frequently reported in patients
      with castration-resistant prostate cancer (CRPC) but there has been no way to
      differentiate PSA rises in CRPC. We investigated whether bone-related serum
      markers differentiate PSA flare from progression in CRPC patients with bone
      metastasis. METHODS: We reviewed CRPC patients with bone metastasis who received
      systemic chemotherapy from 2002 to 2008. Pretreatment baseline and follow-up data
      including age, performance score, PSA, Gleason score, alkaline phosphatase (ALP),
      calcium level, and hemoglobin were evaluated. Pretreatment parameters and follow
      up serum parameters after the first cycle of chemotherapy were included in
      statistical analyses. RESULTS: PSA increased in 38 patients (45.8 %) at the first
      evaluation after chemotherapy. Among the PSA rises, PSA increased continuously or
      did not decrease to the stabilization level by the third evaluation in 22 (26.5
      %) patients, while PSA decreased to the stabilization or response level by the
      third evaluation in 16 (19.3 %). PSA flare occurred in 17 (20.5 %). The
      univariate analyses showed that no baseline parameters were associated with PSA
      flare, but the initial ALP decrease, changed ALP ratio, and median calcium level
      were significantly associated with PSA flare (p = 0.001, p = 0.008 and p = 0.012,
      respectively). Multivariate logistic regression analysis showed that a change in
      the ALP level is an independent predictive factor for PSA flare (p = 0.017).
      CONCLUSIONS: ALP is a useful biomarker to differentiate PSA flare from early PSA
      progression during docetaxel chemotherapy in CRPC patients with bone metastasis.

PMID- 24858570
TI  - Multiple instance learning for classification of dementia in brain MRI.
AB  - Machine learning techniques have been widely used to detect morphological
      abnormalities from structural brain magnetic resonance imaging data and to
      support the diagnosis of neurological diseases such as dementia. In this paper,
      we propose to use a multiple instance learning (MIL) method in an application for
      the detection of Alzheimer's disease (AD) and its prodromal stage mild cognitive
      impairment (MCI). In our work, local intensity patches are extracted as features.
      However, not all the patches extracted from patients with dementia are equally
      affected by the disease and some of them may not be characteristic of morphology
      associated with the disease. Therefore, there is some ambiguity in assigning
      disease labels to these patches. The problem of the ambiguous training labels can
      be addressed by weakly supervised learning techniques such as MIL. A graph is
      built for each image to exploit the relationships among the patches and then to
      solve the MIL problem. The constructed graphs contain information about the
      appearances of patches and the relationships among them, which can reflect the
      inherent structures of images and aids the classification. Using the baseline MR
      images of 834 subjects from the ADNI study, the proposed method can achieve a
      classification accuracy of 89% between AD patients and healthy controls, and 70%
      between patients defined as stable MCI and progressive MCI in a leave-one-out
      cross validation. Compared with two state-of-the-art methods using the same
      dataset, the proposed method can achieve similar or improved results, providing
      an alternative framework for the detection and prediction of neurodegenerative
      diseases.

PMID- 24858571
TI  - Phytophthora sojae effector PsCRN70 suppresses plant defenses in Nicotiana
      benthamiana.
AB  - Phytophthora sojae, an oomycete pathogen, produces a large number of effector
      proteins that enter into host cells. The Crinklers (Crinkling and Necrosis, CRN)
      are cytoplasmic effectors that are conserved in oomycete pathogens and their
      encoding genes are highly expressed at the infective stages in P. sojae. However,
      their roles in pathogenesis are largely unknown. Here, we functionally
      characterized an effector PsCRN70 by transiently and stably overexpressing it in
      Nicotiana benthamiana. We demonstrated that PsCRN70 was localized to the plant
      cell nucleus and suppressed cell death elicited by all the tested cell death
      inducing proteins, including BAX, PsAvh241, PsCRN63, PsojNIP and R3a/Avr3a.
      Overexpression of the PsCRN70 gene in N. benthamiana enhanced susceptibility to
      P. parasitica. The H2O2 accumulation in the PsCRN70-transgenic plants was reduced
      compared to the GFP-lines. The transcriptional levels of the defense-associated
      genes, including PR1b, PR2b, ERF1 and LOX, were also down-regulated in the
      PsCRN70-transgenic lines. Our results suggest that PsCRN70 may function as a
      universal suppressor of the cell death induced by many elicitors, the host H2O2
      accumulation and the expression of defense-associated genes, and therefore
      promotes pathogen infection. 

PMID- 24858572
TI  - Streptomonospora algeriensis sp. nov., a halophilic actinomycete isolated from
      soil in Algeria.
AB  - A halophilic actinomycete strain, designated H27(T), was isolated from a soil
      sample collected from a hypersaline habitat in Djelfa Province (North-Central
      Algeria), and then investigated using a polyphasic taxonomic approach. The strain
      was observed to produce poor aerial mycelium, which formed short chains of oval
      to cylindrical-shaped spores at maturity, and non fragmented substrate mycelium.
      The optimum NaCl concentration for growth was found to be 10-15 % (w/v) and the
      optimum growth temperature and pH were found to be 28-37  degrees C and 6-7,
      respectively. The diagnostic diamino acid in the cell-wall peptidoglycan was
      identified as meso-diaminopimelic acid. The predominant menaquinones of strain
      H27(T) were identified as MK-11 (H4) and MK-10 (H6). The major fatty acids were
      found to be iso-C16:0, anteiso-C17:0, 10 methyl C17:0 and 10 methyl C16:0. The
      diagnostic phospholipids detected were phosphatidylethanolamine,
      diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine and
      phosphatidylinositol. The chemotaxonomic properties of strain H27(T) are
      consistent with those shared by members of the genus Streptomonospora. 16S rRNA
      gene sequence analysis indicated that strain H27(T) is most closely related to
      Streptomonospora alba DSM 44588(T) (98.8 %) and Streptomonospora flavalba DSM
      45155(T) (98.7 %) whereas the DNA-DNA relatedness values between strain H27(T)
      and the two type strains were 17.1 and 57.9 %, respectively. Based on the
      combined genotypic and phenotypic evidence, it is proposed that strain H27(T)
      should be classified as representative of a novel species, for which the name
      Streptomonospora algeriensis sp. nov. is proposed. The type strain is H27(T)
      (=DSM 45604(T) =CCUG 63369(T) =MTCC 11563(T)). 

PMID- 24858573
TI  - Isoptericola rhizophila sp. nov., a novel actinobacterium isolated from
      rhizosphere soil.
AB  - A Gram-positive, yellow pigmented strain, BKS 3-46(T) was isolated from a soil
      sample collected from the rhizosphere of Ficus benghalensis (banyan tree) in
      Bhitarkanika mangrove forest, in the Indian state of Odisha, and subjected to
      polyphasic taxonomic study. The 16S rRNA gene sequence of the strain was
      determined and the sequence analysis showed that strain BKS 3-46(T) should be
      assigned to the genus Isoptericola. The chemotaxonomic data supported this
      taxonomic placement i.e. presence of menaquinone MK-9(H4); major fatty acids
      anteiso C15:0 and iso-C15:0; and phosphatidylglycerol, diphosphatidylglycerol and
      phosphatidylinositol (PI) as major polar lipids. Further phylogenetic analysis of
      the 16S rRNA gene sequence confirmed that the strain BKS 3-46(T) belongs to the
      genus Isoptericola and is closely related to Isoptericola halotolerans MTCC
      11265(T) (98.6 %) followed by Isoptericola nanjingensis MTCC 11633(T) (98.4 %)
      and Isoptericola chiayiensis MTCC 11634(T) (98.1 %). However, the DNA-DNA
      hybridization values obtained between strain BKS 3-46(T) and other related
      strains were well below the threshold that is required for the proposal of a
      novel species. The G+C content of the genomic DNA was determined to be 70.4 mol%.
      The phenotypic and genotypic data showed that the strain BKS 3-46(T) merits the
      recognition as a representative of a novel species of the genus Isoptericola. It
      is proposed that the isolate should be classified in the genus Isoptericola as a
      novel species, Isoptericola rhizophila sp. nov. The type strain is BKS 3-46(T)
      (=MTCC 11080(T)=JCM 19252(T)). 

PMID- 24858574
TI  - Process evaluation of "Girls on the Run": exploring implementation in a physical
      activity-based positive youth development program.
AB  - Many positive youth development programs rely on physical activity as a primary
      program component. Referred to as physical activity-based youth development
      programs, these program designs have great potential for promoting healthy youth
      development. This study examined how one such physical activity-based positive
      youth development program was implemented in order to identify design features
      critical to maximizing positive youth outcomes. This mixed method, multi-site
      process evaluation of Girls on the Run (GOTR) utilized focus groups, site visits,
      and self-report implementation checklists. Implementation scores were calculated
      to assess implementation fidelity across twenty-nine sites, and qualitative data
      were inductively analyzed to identify factors influential for implementation.
      Results reveal variability in how GOTR was implemented. Five themes emerged from
      the data that represented factors serving as facilitators or barriers to
      programmatic implementation. These included contextual/environmental factors
      (e.g., parental involvement, relationships with school personnel), organizational
      factors (e.g., implementation support and responsiveness of staff), program
      specific factors (e.g., curriculum design), coach factors (e.g., existing
      relationships with participants, responsiveness to participant's needs), and
      youth factors (e.g., behavioral and discipline issues). Study findings have
      implications for improving the design of physical activity-based and other
      positive youth development programs, with relevance to evaluators, program
      planners, youth development leaders, and others working with children and youth. 

PMID- 24858575
TI  - Regulation of tissue factor gene expression in monocytes and endothelial cells:
      Thromboxane A2 as a new player.
AB  - Tissue factor (TF) is the primary activator of the coagulation cascade. Under
      normal conditions, endothelial cells (ECs) and blood cells, such as monocytes, do
      not express TF. However, bacterial lipopolysaccharide (LPS) induces TF expression
      in monocytes and this leads to disseminated intravascular coagulation during
      endotoxemia and sepsis. A variety of stimuli induce TF expression in ECs in
      vitro, although it is unclear how much TF is expressed by the endothelium in
      vivo. LPS induction of TF gene expression in monocytic cells and ECs is mediated
      by various intracellular signaling pathways and the transcription factors NF-KB,
      AP-1 and Egr-1. In contrast, vascular endothelial cell growth factor (VEGF)
      induces TF gene expression in ECs via the transcription factors NFAT and Egr-1.
      Similarly, oxidized phospholipids (such as 1-palmitoyl-2-arachidonyl-sn-glycero-3
      phosphorylcholine) induce TF expression in ECs and possibly monocytes via NFAT
      and Egr-1. Thromboxane A2 (TXA2) can now be added to the list of stimuli that
      induce TF gene expression in both monocytes and ECs. Interestingly, inhibition of
      the TX-prostanoid (TP) receptor also reduces TF expression in with tumor necrosis
      factor (TNF)-alpha stimulated ECs and LPS stimulated monocytes, which suggests
      that TP receptor antagonist may be useful in reducing pathologic TF expression in
      the vasculature and blood. 

PMID- 24858576
TI  - Rapid high-throughput characterisation, classification and selection of
      recombinant mammalian cell line phenotypes using intact cell MALDI-ToF mass
      spectrometry fingerprinting and PLS-DA modelling.
AB  - Despite many advances in the generation of high producing recombinant mammalian
      cell lines over the last few decades, cell line selection and development is
      often slowed by the inability to predict a cell line's phenotypic characteristics
      (e.g. growth or recombinant protein productivity) at larger scale (large volume
      bioreactors) using data from early cell line construction at small culture scale.
      Here we describe the development of an intact cell MALDI-ToF mass spectrometry
      fingerprinting method for mammalian cells early in the cell line construction
      process whereby the resulting mass spectrometry data are used to predict the
      phenotype of mammalian cell lines at larger culture scale using a Partial Least
      Squares Discriminant Analysis (PLS-DA) model. Using MALDI-ToF mass spectrometry,
      a library of mass spectrometry fingerprints was generated for individual cell
      lines at the 96 deep well plate stage of cell line development. The growth and
      productivity of these cell lines were evaluated in a 10L bioreactor model of
      Lonza's large-scale (up to 20,000L) fed-batch cell culture processes. Using the
      mass spectrometry information at the 96 deep well plate stage and phenotype
      information at the 10L bioreactor scale a PLS-DA model was developed to predict
      the productivity of unknown cell lines at the 10L scale based upon their MALDI
      ToF fingerprint at the 96 deep well plate scale. This approach provides the basis
      for the very early prediction of cell lines' performance in cGMP manufacturing
      scale bioreactors and the foundation for methods and models for predicting other
      mammalian cell phenotypes from rapid, intact-cell mass spectrometry based
      measurements. 

PMID- 24858577
TI  - To clip or not to clip? Invited comment on Wilhelm et al.: use of self-retaining
      barbed suture for rectal wall closure in transanal endoscopic microsurgery.

PMID- 24858578
TI  - Psycho-echo-biofeedback: a novel treatment for anismus--results of a prospective
      controlled study.
AB  - BACKGROUND: Anismus or non-relaxing puborectalis muscle (PRM), detectable with
      anal/vaginal ultrasound (US), is a cause of obstructed defecation (OD) and may be
      treated with biofeedback (BFB). Many patients with anismus are anxious and/or
      depressed. The aim of this prospective study was to evaluate the outcome of the
      novel procedure psycho-echo-BFB in patients with anismus and psychological
      disorders. METHODS: Patients presenting at our unit with anismus and
      psychological disorders between January 2009 and December 2013, and not
      responding to conventional conservative treatment, were enrolled in the study.
      All underwent four sessions of psycho-echo-BFB, carried out by two psychologists
      and a coloproctologist, consisting of guided imagery, relaxation techniques and
      anal/vaginal US-assisted BFB. A validated score for OD was used, and PRM
      relaxation on straining measured before and after the treatment. PRM relaxation
      was also measured in a control group of 7 patients with normal bowel habits.
      RESULTS: Ten patients (8 females, median age 47 years, range 26-72 years)
      underwent psycho-echo-BFB. The OD score, evaluated prior to and at a median of 25
      months (range 1-52 months) after the treatment, improved in 7 out of 10 patients,
      from 13.5 +/- 1.2 to 9.6 +/- 2.2 (mean +/- standard error of the mean (SEM)), p =
      0.06. At the end of the last session, PRM relaxed on straining in all cases, from
      0 to 7.1 +/- 1.1 mm, i.e., physiological values, not statistically different from
      those of controls (6.6 +/- 1.5 mm). Two patients reported were cured, 3 improved
      and 5, all of whom had undergone prior anorectal surgery, unchanged. No side
      effects were reported. CONCLUSIONS: Psycho-echo-BFB is safe and inexpensive and
      allows all patients with anismus to relax PRM on straining. Previous anorectal
      surgery may be a negative predictor.

PMID- 24858579
TI  - Association of MU-opioid receptor gene (OPRM1) haplotypes with postoperative
      nausea and vomiting.
AB  - Genetic variants, such as single-nucleotide polymorphisms (SNPs), of the MU
      opioid receptor gene (OPRM1) might be associated with individual differences in
      opioid sensitivity, as well as with the incidence and severity of postoperative
      nausea and vomiting (PONV). The goal of the present study was to determine, in a
      cohort of Japanese surgical patients, genotypes and haplotypes of several SNPs in
      the OPRM1 gene, and their association with PONV during the early (first 24 h)
      postoperative period. We examined the incidence and severity of PONV, during the
      first 24 h after surgery, in 85 Japanese patients receiving intravenous patient
      controlled analgesia fentanyl analgesia for postoperative pain control. Eight tag
      SNPs of the OPRM1 gene (rs1799971, A/G; rs510769, G/A; rs4870266, G/A; rs3798683,
      G/A; rs1323042, A/C; rs609623, C/T; rs9397685, A/G; and rs644261, C/G) were
      selected based on their minor allele frequency (>10%) and linkage disequilibrium
      strength (<80%), and genotyped for haplotype analysis and determination of
      associations with PONV. Only one out of eight investigated SNPs, rs9397685, in
      the intronic part of the OPRM1 gene was associated with differences in the
      occurrence and severity of PONV. We also found four common haplotypes with a
      frequency of >10% in the investigated patients, including GGGAACAC (33%),
      AGGGACAC (19%), GGGAACGC (12%), and AGAGACAC (10%). The severity of PONV in
      carriers of the GGGAACGC haplotype was significantly lower than in the carriers
      of the other haplotypes (P < 0.05). One intronic SNP, rs9397685, and haplotypes
      constructed from eight SNPs within the OPRM1 gene locus might be involved in the
      severity of PONV associated with general anesthesia and opioid administration.
      This novel finding, if validated and verified in larger and additional ethnic
      cohorts, might contribute to better knowledge of the contribution of the OPRM1
      gene to PONV.

PMID- 24858580
TI  - Emerging role of IL-17 and Th17 cells in systemic lupus erythematosus.
AB  - Despite the success of targeted therapies in managing immune-mediated
      inflammatory diseases (IMIDs) such as RA, IBDs, MS and psoriasis, unmet needs for
      such approach in SLE are widely recognized. In the past 2years, exciting insights
      supporting previous lines of evidence on the role of the IL-23/IL-17 axis in SLE
      have emerged. This is of particular importance as IL-17 blockers have now moved
      successfully into the clinical space, as illustrated in psoriasis and ankylosing
      spondylitis. However, recent fundamental studies also highlighted unexpected
      aspects of IL-17/Th17 biology whose comprehension may prevent disappointing
      results of IL-17 targeting such as those obtained in Crohn's disease. Therefore,
      establishing a current picture of the IL-17 pre-clinical situation in SLE is
      timely in order to plan future proof-of-concept studies in human. 

PMID- 24858582
TI  - Transintercostal-evoked spinal cord potential in thoracic aortic surgery.
AB  - BACKGROUND: We have developed a novel method of measuring spinal cord-evoked
      potentials with stimulation and recording at the intercostal nerves
      (transintercostal-evoked spinal cord potential: Tic-ESCP). The purpose of this
      study was to examine the feasibility and accuracy of Tic-ESCP during thoracic
      aortic surgery. METHODS: In addition to the conventional electrodes (cranial and
      intrathecal), stimulating and recording electrodes were placed on the intercostal
      nerves that were located at a cephalad and caudal level relative to the aneurysm
      after the pleura on the intercostal nerves was opened. Specially designed hook
      type electrodes were anchored to the nerves and surroundings atraumatically and
      fixed on the pleura. The conventional transcranial motor-evoked potential (Tc
      MEP) and Tic-ESCP were recorded simultaneously. Eight patients were examined in
      this study. RESULTS: In all patients, Tic-ESCP could be clearly recorded with
      biphasic waveforms consisting of first a positive wave and a subsequent negative
      wave. In all 8 patients, the waveform of Tc-MEP and Tic-ESCP changed during
      aortic reconstruction. In 2 cases, the waveform of Tc-MEP and Tic-ESCP decreased
      below 50% of baseline during aortic clamping and the intercostal arteries were
      reconstructed with no resultant spinal cord injury. In 1 case with a shaggy
      aorta, Tc-MEP and Tic-ESCP had different values and each evoked potential could
      have reflected that regional spinal cord infarction and paraplegia had occurred.
      CONCLUSIONS: Tic-ESCP was clinically feasible and changes were compatible with
      the conventional Tc-MEP. The Tic-ESCP waveforms were simple and appeared to be
      specific to the spinal cord within the target range, in contrast to the other
      evoked potentials which are multimorphic and reflect the amplitudes at the brain
      and multiple levels of the spinal cord.

PMID- 24858581
TI  - Regulatory T cells control diabetes without compromising acute anti-viral
      defense.
AB  - While previous reports have demonstrated the efficacy of regulatory T cell
      therapy in the prevention of diabetes, systemic immunocompromise and Treg
      instability remain key safety concerns. Here we examined the influence of induced
      Treg (iTreg) cell therapy on anti-viral host defense and autoimmune T cell
      responses during acute viral infection in a murine model of autoimmune diabetes.
      Protective transfers of iTregs maintained IL-10 expression, expanded in vivo and
      controlled diabetes, despite losing FoxP3 expression. Adoptive transfer of iTregs
      affected neither the primary anti-viral CD8 T cell response nor viral clearance,
      although a significant and sustained suppression of CD4 T cell responses was
      observed. Following acute viral clearance, iTregs transferred early suppressed
      both CD4 and CD8 T cell responses, which resulted in the reversion of diabetes.
      These observations indicate that iTregs suppress local autoimmune processes while
      preserving the immunocompetent host's ability to combat acute viral infection. 

PMID- 24858583
TI  - Octogenarians develop infrapopliteal arterial occlusive disease in the absence of
      traditional risk factors.
AB  - BACKGROUND: With increasing longevity, a growing proportion of patients who
      present with lower extremity peripheral arterial disease (LE-PAD) are >=80 years
      old. While smoking and diabetes mellitus (DM) have traditionally been the main
      risk factors associated with PAD, we noted a pattern of severe infrapopliteal PAD
      in patients >=80 years old in the absence of these traditional risk factors. As
      recognition of patterns of disease affects decisions regarding diagnostic and
      therapeutic approach, we sought to confirm this observation. METHODS: A single
      center retrospective review was performed on all patients who underwent lower
      extremity arteriography between March 2007 and September 2009. Arteriograms were
      scored in a blinded fashion. Any infrapopliteal PAD was defined as one or more
      infrapopliteal arteries with either >50% stenosis or total occlusion. Severe
      infrapopliteal PAD was defined as 2 or more infrapopliteal arteries with >50%
      stenosis or total occlusion. Fisher's exact test and 2-sample t-test or Wilcoxon
      rank-sum test were used for analysis. RESULTS: Two hundred ninety-seven patients
      comprised the study population. Eighty-two percent (= 145/176) of those <=70
      years old versus 96% (= 46/48) of those >=80 years old had any infrapopliteal PAD
      (P = 0.02). Thirty percent of patients >=80 years old with infrapopliteal PAD had
      no history of DM or smoking, while only 5% of younger patients had infrapopliteal
      PAD in the absence of DM or smoking (P < 0.0001). A similar pattern was seen for
      severe infrapopliteal PAD. Tissue loss was an indication for lower extremity
      arteriography in 45% of those <=70 years of age versus 65% of those >=80 (P =
      0.022). CONCLUSIONS: A significant proportion of patients >=80 years of age with
      PAD develop arterial disease in the infrapopliteal pattern in the absence of the
      traditional risk factors of smoking and DM. Our data also showed that this
      pattern of disease is significantly associated with tissue loss and critical limb
      ischemia, particularly in patients >=80 years of age. Primary care providers need
      to be educated to suspect ischemic etiology for foot pain and ulcers in elderly
      patients not otherwise thought to have risk factors associated with PAD. Vascular
      specialists need to anticipate this pattern of disease when planning
      interventions. As smoking becomes less prevalent and as the population ages,
      octogenarians with severe infrapopliteal arterial occlusive disease will become a
      larger proportion of the patients treated by vascular specialists.

PMID- 24858584
TI  - Severe symptomatic stenosis of visceral and renal arteries leading primary
      antiphospholipid syndrome diagnosis.
AB  - Antiphospholipid syndrome (APS) is an autoimmune disorder with combination of at
      least 1 clinical and 1 laboratory criterion as defined by the SAPPORO statement.
      Clinical criteria result from vascular thrombosis that can affect artery, venous,
      or small vessel in any tissue or organ. Arterial stenosis is a rare lesion
      involved in APS, affecting mainly renal or intracranial arteries. We reported a
      case of a 33-year-old woman with abdominal angina and high blood pressure (BP).
      Imaging showed tight, not calcified, and hypodense stenosis of mesenteric
      superior artery and left renal artery, and a thrombosis of the celiac trunk.
      Treatment was digestive rest followed by angioplasty and stenting of mesenteric
      and renal artery, anticoagulation, antiplatelet, and statin therapy. Normal BP
      and digestive function were obtained postoperatively. Biological tests showed a
      positive lupus anticoagulant at diagnosis and at 12 weeks, which allowed us to
      make the diagnosis of APS. Physiopathology of stenosis in APS remains unclear but
      suggests arterial wall partial thrombosis, accelerated atherosclerosis, and/or
      proliferation of smooth muscle cells. We recommend screening of arterial stenosis
      in patients with APS and arterial symptoms, and inversely, searching for APS in
      young patients with atypical arterial stenosis to allow optimal therapy. 

PMID- 24858585
TI  - Fungal infection of aortic Endograft because of Aspergillus fumigatus.
AB  - A 59-year-old male, referred to our center with a ruptured aortic aneurysm,
      underwent urgent endovascular repair and femoro-femoral crossover bypass. An
      endograft infection because of Aspergillus fumigatus occurred about 20 days after
      surgery. We removed the endograft and femoral prosthesis and we then performed an
      aorto-bi-iliac bypass with autogenous reversed superficial femoral veins. Five
      days after surgery, the patient died. Microbiological examination and postmortem
      examination showed the presence of A. fumigatus in femoral prosthesis, aortic
      wall, and periaortic exudate. 

PMID- 24858586
TI  - Preservation of pelvic circulation in one-stage endovascular repair of bilateral
      hypogastric artery aneurysms.
AB  - Bilateral hypogastric artery aneurysms (HAAs) are relatively rare conditions that
      pose increased management difficulties. We report a case of one-stage
      endovascular repair of bilateral HAAs preserving pelvic circulation. A 67-year
      old asymptomatic man with bilateral HAAs (4-cm right and 3.9-cm left) was
      successfully treated with an endovascular approach. The aneurysmal sac of the
      right hypogastric artery (HA) was embolized first and 2 covered stent grafts were
      deployed into the HA. Coil embolization of the left HAA was then performed
      followed by deployment of a covered stent graft to the common and external iliac
      arteries. Final angiography revealed complete exclusion of the aneurysms without
      endoleaks and with preservation of the pelvic flow. At the 18-month follow-up,
      the patient remained asymptomatic with good patency of the stent grafts. This
      case demonstrates an alternative endovascular approach for the treatment of
      bilateral HAAs that minimizes the risk of ischemic complications by preserving
      pelvic circulation. 

PMID- 24858588
TI  - Hybrid treatment of symptomatic chronic isolated carotid bifurcation.
AB  - Total chronic occlusion of the common carotid artery with patent internal and
      external carotid arteries can induce cerebral embolism and hypoperfusion. We
      report a hybrid approach that was used to treat 2 patients presented with
      symptomatic chronic occlusion of the common carotid artery and ipsilateral
      internal carotid stenosis. Antegrade recanalization and retrograde stenting of
      the common carotid artery was performed in both patients associated to carotid
      bulb endarterectomy. Fresh thrombus observed in the distal common carotid stump
      was responsible for the embolic cerebral lesions and patients' previous symptoms.
      Patients remain asymptomatic at the 23rd- and 18th-month follow-up, respectively.

PMID- 24858587
TI  - Brachial plexus lipomata presenting with neurogenic and venous thoracic outlet
      syndrome: case reports and review of the literature.
AB  - BACKGROUND: Compression of the brachial plexus causing neurogenic symptoms is
      involved in most cases referred to vascular surgeons for consideration of
      treatment of thoracic outlet syndrome (TOS). The causative factor of the
      compression can be difficult to diagnose with multiple pathologies implicated.
      METHODS: We present 2 rare cases of supraclavicular lipomata causing compression
      of the neurovascular structures in the thoracic outlet. The only 6 other cases of
      brachial plexus lipomata were described to our knowledge in the literature
      worldwide. RESULTS: We highlight that there are a small number of neurogenic TOS
      cases where the causative pathology can be successfully managed by surgery with
      expectation of a good recovery. CONCLUSIONS: Surgeons operating on these lesions
      can expect good symptom resolution for their patients.

PMID- 24858589
TI  - Neurological and electrophysiological parameters as outcome measurements for
      peripheral arterial occlusive disease.
AB  - BACKGROUND: Ischemic monomelic neuropathy is not an uncommon complication of
      peripheral arterial occlusive disease (PAOD). However, many investigators have
      used revascularization, limb salvage, and complete wound healing rates instead of
      neurologic and electrophysiological parameters as outcome measurements of PAOD.
      The aim of the study is to investigate the neurologic and electrophysiological
      parameters associated with PAOD and to find the ideal tools for assessing PAOD.
      METHODS: A total of 38 PAOD patients (68.5 +/- 8.1 years old, male:female = 32:6)
      with a total of 76 lower limbs were enrolled in the study. Primary outcomes were
      neurological symptoms scores (NSSs) and neurological impairment scores (NISs) for
      the lower extremities. Secondary outcomes were taken from nerve conduction
      studies (NCSs) and included the following: sensory nerve action potential (SNAP)
      amplitudes of the sural, superficial peroneal, and medial plantar nerves and the
      compound muscle action potential (CMAP) amplitudes of the posterior tibial and
      common peroneal nerves. RESULTS: Female patients with old age, hypertension, low
      body weights, low body mass indices (BMIs), decreased ankle-brachial indices
      (ABIs), and poorer Fontaine classifications exhibited worse NSSs and NISs
      indices. Patients with old age, diabetes mellitus, hypertension, histories of
      social alcohol consumption, low body weights, low BMIs, and poorer Fontaine
      classifications exhibited decreased SNAP and CMAP amplitudes in the sensory and
      motor NCSs. Decreased ABI was associated with decreased SNAP amplitudes in the
      sensory NCSs. CONCLUSIONS: Neurologic and electrophysiological parameters can be
      good tools for the assessment of PAOD. NSSs and NISs are particularly good
      candidates for outcome measures of PAOD.

PMID- 24858590
TI  - Endovascular treatment of iatrogenic injury to the retrohepatic inferior vena
      cava.
AB  - Iatrogenic injury of the inferior vena cava (IVC) is a rare event with
      potentially devastating sequelae. Only a handful of case reports are available in
      the literature describing successful endovascular techniques to manage this
      complication. We present the case of a patient with injury to the retrohepatic
      IVC resulting in life-threatening hemorrhage which was controlled with
      endovascular stent grafts. 

PMID- 24858591
TI  - Middle colic artery branch aneurysm presenting as spontaneous hemoperitoneum.
AB  - Rupture of a middle colic artery branch aneurysm is a rare presentation of
      visceral artery aneurysms. We report a case of a 53-year-old male complaining of
      acute-onset abdominal pain found to have a massive intraabdominal hematoma
      secondary to a leaking branch aneurysm of the middle colic artery. The patient
      underwent laparotomy and ligation of the aneurysm after an attempted endovascular
      intervention. Following the case report, a review of the literature entailing
      incidence, presentation, possible etiologies, and potential management strategies
      is presented. 

PMID- 24858592
TI  - Urinary cystatin C as an early biomarker of acute kidney injury after open and
      endovascular abdominal aortic aneurysm repair.
AB  - BACKGROUND: Acute kidney injury (AKI) after open repair (OR) and endovascular
      repair (EVAR) of abdominal aortic aneurysm (AAA) is associated with increased
      mortality and hospital costs. Early detection of AKI is critical to prevent its
      progression. Recent findings demonstrate that elevated levels of urinary cystatin
      C (uCysC) may reflect tubular dysfunction. We prospectively evaluated whether
      uCysC can detect renal dysfunction earlier than serum creatinine (sCr). METHODS:
      In a prospective study, 126 consecutive patients (mean age +/- SD, 69.1 +/- 8.66
      years) with AAA (EVAR = 87, OR = 39) were enrolled. sCr and uCysC were measured
      preoperatively (baseline) and at 6, 24, and 48 hr postoperatively. A final
      measurement was made on day 5. AKI was defined according to Acute Kidney Injury
      Network criteria. RESULTS: The incidence of AKI was significantly higher (chi(2)
      test, P < 0.05) in the OR group (n = 13, 33%) than in the EVAR group (n = 15,
      17%). The baseline median (interquartile range) value of uCysC was significantly
      higher (t-test, P < 0.05) in patients of both groups (OR-EVAR) who developed AKI
      from those who did not (OR/AKI group: 0.06 [0.02-0.12] mg/L, EVAR/AKI group: 0.08
      [0.05-0.11] mg/L versus no-AKI subjects: 0.04 [0.02-0.07] mg/L). Subsequent
      analysis showed that at 6 hr postoperatively, the patients who developed AKI
      increased their uCysC levels significantly from baseline (OR/AKI group: 0.58
      [0.42-0.70] mg/L, EVAR/AKI group: 0.59 [0.30-1.07] mg/L). The median value of
      uCysC in AKI patients increased at 24 hr (OR/AKI group: 1.37 [0.78-3.40] mg/L,
      EVAR/AKI group: 2.11 [0.70-2.42] mg/L) and peaked at 48 hr (OR/AKI group: 6.16
      [1.74-10.73] mg/L, EVAR/AKI group: 2.57 [1.21-7.40] mg/L), while no increase was
      observed among those who did not develop AKI at the same time points (0.06 [0.04
      0.14] vs. 0.08 [0.04-0.19] mg/L). The diagnostic accuracy of uCysC at 6 hr post
      surgery was excellent (area under the curve - receiver-operating characteristic
      [AUC-ROC] = 0.968), significantly higher than sCr (AUC-ROC = 0.844) and a cutoff
      value set at 0.30 mg/L can diagnose AKI with a sensitivity of 85.71% and a
      specificity of 98.97%. CONCLUSIONS: uCysC is superior to sCr in the early
      diagnosis of AKI following open and endovascular AAA repair.

PMID- 24858593
TI  - Salvage of severe ischemic lower limb having peak creatine phosphokinase level
      exceeding 200,000 IU/L treated by continuous hemodiafiltration.
AB  - We performed revascularization by an anti-anatomical bypass in a 40-year-old man
      with extended ischemia of both legs beyond 12 hr after onset because of traumatic
      aortic dissection. This patient developed myonephropathic metabolic syndrome,
      including renal and circulatory failure accompanied by a creatine phosphokinase
      level above 200,000 IU/L. Nevertheless, his bilateral affected limbs were
      salvaged by intensive care based on aggressive hemocatharsis with continuous
      hemodiafiltration with treatment for poor hemodynamics and respiratory distress. 

PMID- 24858594
TI  - Magnetic resonance imaging: occult popliteal artery entrapment syndrome in a
      young soldier.
AB  - BACKGROUND: Popliteal artery entrapment syndrome (PAES) is frequently
      misdiagnosed because of symptom overlap with other conditions and lack of a
      definitive diagnostic modality. The incidence is widely variable, although it
      should be considered in all patients under 50 years with symptoms of lower
      extremity claudication. Long-term sequelae of PAES include critical limb
      ischemia, arterial occlusion, and aneurysm formation caused by repetitive
      external compression. METHODS: We review the case of a 27-year-old soldier
      originally treated for exertional compartment syndrome with fasciotomies without
      relief of symptoms. Magnetic resonance imaging (MRI) failed to demonstrate an
      aberrant slip of the gastrocnemius muscle, which was ultimately found and
      released on surgical exploration. RESULTS: Surgical exploration and release of an
      aberrant band of gastrocnemius muscle through a medial approach resulted in
      significant relief of symptoms and improvement of walking distance. CONCLUSIONS:
      Healthy athletes without peripheral vascular disease and symptomatic calf and
      foot claudication should have an early referral to vascular surgery. The risk of
      false-negative MRI warrants further investigation into provocative, noninvasive
      imaging modalities to properly classify PAES. This report reviews the literature
      to discuss the diagnostic challenges, natural history of disease, and surgical
      interventions for PAES.

PMID- 24858595
TI  - Treatment results for spontaneous isolated superior mesenteric artery dissection
      according to our previous guidelines and collective literature review.
AB  - BACKGROUND: Isolated superior mesenteric artery dissection (ISMAD) is not a rare
      disease. However, its optimal treatment strategy has not yet been established.
      METHODS: This study included 13 consecutive patients with ISMAD who were treated
      between April 2010 and July 2013 according to published treatment guidelines.
      Through a literature search, 10 studies on treatments and outcomes for ISMAD that
      were published from 2007 to the present were analyzed. RESULTS: In the present
      study, 11 patients had acute onset abdominal pain and 2 patients were
      asymptomatic. Twelve patients were treated with conservative treatment, whereas 1
      patient underwent coil embolization. In the literature review, initial
      conservative treatment, endovascular procedure, and surgical repair were done in
      172, 25, and 14 patients, respectively. Bowel resection was done in 8 patients
      (3.7%) due to bowel necrosis. Conservative treatment failed in 15 patients (6.8%)
      during follow-up. CONCLUSIONS: If bowel necrosis or arterial rupture was not
      present, conservative treatment of ISMAD was a safe and effective treatment.
      Aneurysmal type IV patients on computed tomography scan should be carefully
      followed up, and if there is a recurrence of pain or aneurysmal progression, an
      endovascular procedure could be safely performed.

PMID- 24858597
TI  - Childhood verbal abuse: a risk factor for depression in pre-bariatric surgery
      psychological evaluations.
AB  - The present study evaluated the importance of multimodal assessment of childhood
      verbal abuse (CVA) in pre-bariatric surgery psychological evaluations, and the
      role of CVA as a predictor of depression. Data from the psychological evaluations
      of 184 pre-bariatric surgery patients were retrospectively examined. Using two
      self-report measures and an interview-based screen, 52.2 % of participants
      reported experiencing some form of CVA; conversely, assessments of CVA based on
      only one measure yielded significantly lower prevalence rates. Endorsement of CVA
      on multiple measures was associated with more severe depressive symptomatology
      and greater likelihood of mood disorder diagnosis. Based on these data, a self
      report measure and interview-based screen for CVA should be included in pre
      bariatric psychological evaluations; either of these assessments may be conducted
      via a single-item screen. Lastly, patients who endorse CVA on multiple measures
      should be monitored closely for symptoms of depression post-surgery. 

PMID- 24858598
TI  - Pharmaceutical care for patients with COPD in Belgium and views on protocol
      implementation.
AB  - BACKGROUND: A protocol-based pharmaceutical care program (the PHARMACOP-protocol)
      focusing on patient counselling during prescription filling has shown to be
      effective in patients with chronic obstructive pulmonary disease (COPD). However,
      implementation of this protocol in daily practice has not yet been studied.
      OBJECTIVE: To describe current implementation level of the items included in the
      PHARMACOP-protocol in Belgian community pharmacies and to evaluate pharmacists'
      perspectives on the implementation of this protocol in daily practice. METHOD: A
      cross-sectional study was conducted from April to June 2012, in randomly selected
      community pharmacies in Flanders. Pharmacists were questionned using structured
      interviews. RESULTS: 125 pharmacies were contacted and 80 managing pharmacists
      (64 %) participated. In >70 % of pharmacies, 4/7 protocol items for first
      prescriptions and 3/5 protocol items for follow-up prescriptions were already
      routinely implemented. For first and follow-up prescriptions, respectively 39 (49
      %) and 34 pharmacists (43 %) stated they would need to spend at least 5 min extra
      to offer optimal patient counselling. Most mentioned barriers preventing protocol
      implementation included lack of time (80 %), no integration in pharmacy software
      (61 %) and too much administrative burden (58 %). CONCLUSION: Approximately 50 %
      of the PHARMACOP-protocol items are currently routinely provided in Belgian
      community pharmacies. Nearly all interviewed pharmacists are willing to implement
      the protocol fully or partially in daily practice.

PMID- 24858599
TI  - Modulation of tissue inflammatory response by histamine receptors in scorpion
      envenomation pathogenesis: involvement of H4 receptor.
AB  - The inflammatory response caused by scorpion venoms is a key event in the
      pathogenesis of scorpion envenomation. This response was assessed in the cardiac,
      pulmonary, and gastric tissues of envenomed mice. The results reveal an increase
      of permeability in cardiac, pulmonary, and gastric vessels accompanied by an
      edema-forming, inflammatory cell infiltration, and imbalanced redox status. These
      effects are correlated with severe tissue alterations and concomitant increase of
      metabolic enzymes in sera. Pretreatment of mice with antagonists of H1, H2, or H4
      receptors markedly alleviated these alterations in the heart and lungs.
      Nevertheless, the blockade of the H3 receptor slightly reduced these disorders.
      Histamine H2 and H4 receptors were the most pharmacological targets involved in
      the gastric oxidative inflammation. These findings could help to better
      understand the role of histamine in scorpion venom-induced inflammatory response
      and propose new therapy using as targets the H4 receptor in addition to histamine
      H1 and H2 receptors to attenuate the induced inflammatory disorders encountered
      in scorpion envenoming. 

PMID- 24858601
TI  - Have 3D endoscopes succeeded in neurosurgery?

PMID- 24858600
TI  - STAT1 regulates MD-2 expression in monocytes of sepsis via miR-30a.
AB  - Sepsis is a major cause of morbidity and mortality in critically ill patients. MD
      2 is a 25-kDa lipopolysaccharide (LPS)-binding protein that forms a heterodimer
      with TLR42, but its regulation in sepsis is not clear. This study aims to
      investigate the molecular mechanism of regulation of MD-2. Inflammation cytokines
      in monocytes were analyzed by real-time RT-PCR and ELISA, and it was found that
      IL-10 was elevated significantly in the monocytes with LPS treatment. And then,
      when the cells were treated with IL-10, STAT1 was activated in the monocytes
      using Western blotting. It was also found that STAT1 could enhance MD-2
      expression on transcriptional and posttranscriptional levels. Finally, miR-30a
      was predicted to the molecule that may regulate STAT1 expression. It was verified
      that STAT1 was a new target gene of miR-30a. miR-30a could inhibit IL-10-induced
      cytokine release by targeting STAT1-MD-2 in monocytes. In conclusion, this study
      for the first time demonstrated that miR-30a inhibits MD-2 expression by
      targeting of STAT1 in human monocytes. 

PMID- 24858602
TI  - Cholera outbreaks in South and Southeast Asia: descriptive analysis, 2003-2012.
AB  - We conducted descriptive analysis of available information regarding the
      epidemiology of cholera outbreaks in South and Southeast Asia during 2003-2012.
      Information from 58 articles, 8 reports, and World Health Organization databases
      were analyzed. Overall, 113 cholera outbreaks were studied in South and Southeast
      Asia during the past 10 years. The majority of the outbreaks (69%) occurred in
      Southeast Asia, including India (52%). The highest number of outbreaks was
      observed in 2004 (25.7%). The most commonly identified source was contaminated
      water: however, in some countries, the spread of cholera was facilitated via
      contaminated seafood (e.g., Myanmar, Thailand, and Singapore). Several genotypes
      and phenotypes of Vibrio cholerae, the causative agent of cholera, were
      identified in the outbreaks, including V. cholerae O1 El Tor (Ogawa and Inaba)
      and V. cholerae O139. The emergence of multidrug-resistant V. cholerae strains
      was a major concern. Cholera-related mortality was found to be low across the
      outbreaks, except in Orissa, India (currently Odisha) during 2007, where the case
      fatality rate was 8.6%. Potential limitations included underreporting,
      discrepancies, possible exclusion of nonindexed reports, and incomprehensive
      search terms. The provision of safe water and proper sanitation appear to be
      critical for the control of further spread of cholera in South Asian and
      Southeast Asian regions. 

PMID- 24858603
TI  - Molecular analysis of ciprofloxacin resistance among non-typhoidal Salmonella
      with reduced susceptibility to ciprofloxacin isolated from patients at a tertiary
      care hospital in Kuala Lumpur, Malaysia.
AB  - We investigated the prevalence of non-typhoidal Salmonella (NTS) with "reduced
      susceptibility to ciprofloxacin" (RS-Cip) (minimum inhibitory concentration
      [MIC], 0.12-1.0 MUg/mL) as well as their resistance genes in 75 NTS isolates (53
      from stool, 21 from blood, and 1 from urine) from patients at a tertiary care
      Malaysian hospital between January and December 2009. RS-Cip was detected in
      24/75 (32.0%) isolates. Using the ciprofloxacin MIC interpretive criteria for
      Salmonella in the Clinical and Laboratory Standards Institute 2013 guidelines,
      51/75 (68.0%) isolates were found to be sensitive, 22/75 (29.3%) were
      intermediate, and 2/75 (2.7%) were resistant to ciprofloxacin. The 24 isolates
      that were intermediate or resistant to ciprofloxacin were the same isolates
      categorized as having RS-Cip. Among the 23 tested isolates with RS-Cip, the qnrS
      gene was detected in 17/23 (73.9%) and single gyrA mutations were detected in
      6/23 (26.1%) (Asp87Tyr [n = 3], Asp87Asn [n = 2], and Ser83Phe [n = 1]). A parC
      (Thr57Ser) mutation was detected in 13/23 (56.5%) isolates, coexisting with
      either a qnrS gene or a gyrA mutation. The high incidence of the qnrS gene among
      isolates with RS-Cip needs to be monitored because qnr genes can spread via
      plasmids and aid in the emergence of increased resistance levels. 

PMID- 24858605
TI  - Effect of serum components on biofilm formation by Aspergillus fumigatus and
      other Aspergillus species.
AB  - Biofilm production by microorganisms is critical for their pathogenicity. Serum
      promotes biofilm production by Aspergillus fumigatus; however, its effects on
      other Aspergillus spp. have not been reported. We analyzed biofilm formation by
      five Aspergillus spp., i.e., A. fumigatus, A. flavus, A. nidulans, A. niger, and
      A. terreus, and examined the effects of serum/serum proteins such as fetal bovine
      serum (FBS), fetuin A, and bovine serum albumin (BSA) on hyphal growth, hyphal
      branching, and extracellular matrix (ECM) formation. The antifungal
      susceptibility of A. fumigatus isolates that formed biofilms was also examined.
      All serum/serum proteins promoted the growth of all these fungal species; growth
      promotion was most evident with FBS, followed by fetuin A and BSA. This effect
      was most evident in case of A. fumigatus and least evident in case of A. terreus.
      Electron microscopy showed thick ECM layers surrounding fungal cell walls after
      culture with FBS, particularly in A. fumigatus. An increase in hyphal branching
      caused by fetuin A was the highest in case of A. fumigatus and A. nidulans.
      Biofilm-forming A. fumigatus showed resistance to most antifungal agents,
      although a synergism of micafungin and amphotericin B was suggested. Our results
      indicate that serum promotes biofilm formation, including thick ECM, by many
      Aspergillus spp., particularly A. fumigatus, and that this may be closely related
      to its virulence. 

PMID- 24858606
TI  - Vaccine-associated measles in the low-incidence country of Korea over a 10-year
      period.
AB  - As the incidence of measles decreases, cases reported as suspected measles will
      increasingly involve rash associated with measles vaccination itself. In this
      study, we assessed vaccine-associated measles cases reported in Korea between
      2002 and 2012 using a standardized assessment and following by the World Health
      Organization case definition criteria. We retrospectively analyzed data regarding
      (i) wild-type measles and (ii) vaccine-associated measles in patients aged 12-23
      months. The presence or absence of fever, rash, cough, coryza, conjunctivitis,
      and Koplik spots were reviewed. Males were more likely to be reported with
      vaccine-associated measles than with wild-type measles (68% vs. 47%, P < 0.05).
      The number of patients with wild-type measles peaked between April and July,
      whereas that of patients with vaccine-associated measles remained relatively
      constant throughout the year. However, after excluding the cases reported during
      the 2007 outbreak in Korea, the trend was similar between the two groups. Cough,
      coryza, and conjunctivitis were more likely to be present in patients with wild
      type measles (32-61% vs. 10-43%, P < 0.05); conversely, the absence of these
      symptoms was noted in most patients with vaccine-associated measles. We therefore
      conclude that cough, coryza, and conjunctivitis may be useful as key positive
      findings to distinguish between wild-type measles and vaccine-associated measles
      infection among 12-23-month-old patients in a country with a low incidence of
      measles. 

PMID- 24858607
TI  - Avian-like A (H1N1) swine influenza virus antibodies among swine farm residents
      and pigs in southern China.
AB  - Infection of human with avian-like A (H1N1) swine influenza virus (SIV)
      occasionally occurs in China, suggesting a potential risk of cross-species
      transmission of the swine influenza H1N1 virus from pigs to humans, particularly
      to those having direct contact with pigs. A seroepidemiological study was
      conducted to assess the prevalence of antibodies against the avian-like A (H1N1)
      SIV among swine farm residents and pigs in southern China to evaluate the risk of
      infection to swine farm workers. Hemagglutination inhibition (HI) assays revealed
      that 11.17% (61/546) of the sera samples from swine farm residents in southern
      China were positive for antibodies against the avian-like A (H1N1) SIV. The
      difference in numbers of antibody-positive samples obtained from swine farm
      residents and a control group of healthy city residents was statistically
      significant (P = 0.031). In addition, 219 of the 1,180 serum samples from pigs
      were positive for the antibodies against an avian-like A (H1N1) SIV,
      A/swine/Guangdong/SS1/2013(H1N1), as assessed by HI. The data suggest that
      occupational exposure of swine farm residents and veterinarians in southern China
      to pigs may increase their risk of acquiring avian-like A (H1N1) SIV infection.
      According to a special pig farming model in southern China, the staff and
      residents are in close contact with infected pigs and may be among the first to
      become infected. 

PMID- 24858608
TI  - High-risk behavior of HIV/AIDS among females sex workers in Bangladesh: survey in
      Rajshahi City.
AB  - Female sex workers (FSWs) and their clients are one of the major sources of
      spread of HIV/AIDS in Bangladesh. The purpose of this study was to determine the
      rate of unprotected sex among FSWs in Rajshahi City, Bangladesh. A total of 200
      FSWs were randomly selected for the survey from February to September 2012. The
      age range of FSWs was 16-41 years (average age, 24.52 +/- 6.26 years), and the
      majority of these women (84.4%) were married. More than 88% of FSWs reported
      practicing unprotected sex because of clients' insistence. Further analysis
      showed a significantly higher rate of protected sex among unmarried FSWs (P <
      0.01). Approximately 32% of FSWs did not undergo voluntary counseling and testing
      (VCT) for HIV, and this factor was significantly associated with the education
      level (P < 0.01), age (P < 0.01), and economic status (P < 0.05). Furthermore,
      89.5% respondents did not ask their new clients about VCT/HIV status, and this
      factor was associated with the resident area (P < 0.05), age (P < 0.05), and
      economic status (P < 0.01) of FSWs. Authorities in this country should focus
      their HIV/AIDS prevention efforts on illiterate FSWs, married FSWs, and FSWs aged
      below 21 years or above 30 years. 

PMID- 24858604
TI  - Pandemic influenza A (H1N1) infection in pregnant and nonpregnant women in Spain
      (2009-2010).
AB  - The present study aimed to compare the main features of infection with pandemic
      influenza A virus in pregnant and nonpregnant women admitted to hospitals in
      Spain during the first waves of the 2009-2010 influenza pandemic. This was a
      prospective (November 2009 to June 2010), multicenter observational study. All
      cases were women of reproductive age who had not been vaccinated against seasonal
      or pandemic influenza A. Influenza infection was confirmed by reverse
      transcription-polymerase chain reaction (RT-PCR). The sociodemographic and
      clinical data of all cases were reviewed. A total of 219 inpatients, including 49
      pregnant women and 170 nonpregnant women, were enrolled in the study upon
      admission to participating hospitals. The most substantially different symptoms
      between the groups were respiratory distress and unilobar consolidation, both of
      which were more frequent among nonpregnant women. Antibiotics and systemic
      corticosteroids were more frequently used in nonpregnant women; however, there
      were no differences in the rates of treatment with antivirals. Our findings
      indicated that the compared with nonpregnant women, pregnant women in this study
      did not have significantly different symptoms and were not at increased risk of
      complications from pandemic influenza virus infection. 

PMID- 24858609
TI  - Epidemiology and etiology of acute encephalitis syndrome in North India.
AB  - Acute encephalitis syndrome (AES) is a major public health problem in eastern
      Uttar Pradesh, claiming thousands of lives every year. Here we report the common
      viral etiologic agents of AES and its epidemiology in the vicinity of Lucknow in
      Uttar Pradesh, North India. Cerebrospinal fluid (CSF) samples collected from
      patients with AES, who were referred to a viral diagnostic laboratory from
      January 2011 to December 2012, were tested for IgM antibodies against Japanese
      encephalitis virus (JEV), dengue virus (DV), herpes simplex virus (HSV), measles
      virus, mumps virus, varicella zoster virus (VZV), and enterovirus using
      commercial enzyme immuno-assays. Of the 1,578 enrolled patients, JEV was the most
      commonly detected (16.2%), followed by DV (10.8%), HSV (9.3%), measles virus
      (8.9%), mumps virus (8.7%), VZV (4.4%), and enterovirus (0%). Co-positivity with
      more than 1 virus was observed in 12 patients. The demographic distribution of
      patients pertaining to age, sex, and geographic and seasonal variation is
      discussed. Maximum mortality was caused by JEV infection, while patients with HSV
      infection had maximum residual neuro-psychiatric disability. JEV and DV are the
      chief causative agents of AES in North India, although other viruses should also
      be considered in a differential diagnosis. 

PMID- 24858610
TI  - Shiga toxin 2f-producing Escherichia albertii from a symptomatic human.
AB  - The previously identified Shiga toxin (Stx) 2f-producing Escherichia coli
      O115:HNM strain F08/101-31, isolated from a symptomatic human, was confirmed to
      be E. albertii in the present study by whole genome DNA-DNA hybridizations, by
      sequencing (cpn60, dnaJ, and 16S rRNA genes), and by multi-locus sequence typing.
      The F08/101-31 strain was originally identified as E. coli rather than the
      relatively new bacterial species E. albertii, which was first described in 2003,
      because it did not display any of the biochemical characteristics of E. albertii.
      This new classification will impact public health management strategies in Japan
      because the present study showed that some E. albertii strains, which are often
      misidentified as E. coli, produce Stx and likely cause diarrhea in humans.
      Therefore, further guidelines for the management and identification of Stx
      producing E. albertii are required in Japan. 

PMID- 24858611
TI  - Development of a novel Dengue-1 virus replicon system expressing secretory
      Gaussia luciferase for analysis of viral replication and discovery of antiviral
      drugs.
AB  - Replicon systems have been used for high-throughput screening of anti-dengue
      virus (anti-DENV) inhibitors and for understanding mechanisms of viral
      replication. In the present study, we constructed novel DENV-1 replicons encoding
      Gaussia luciferase that was secreted into the culture medium. Two types of
      constructs were generated: RNA-based and DNA-based. Each type was translated in
      an internal ribosome entry site (IRES)-dependent or IRES-independent manner.
      Among these constructs, the DNA-based replicon employing IRES-dependent
      translation (DGL2) produced the highest titer. Luciferase levels in the culture
      medium revealed that the DGL2 replicon was inhibited by ribavirin (a well-known
      DENV inhibitor) at levels similar to those measured for drug inhibition of multi
      round DENV-1 infection. These results indicate that the DNA-based IRES-driven
      DENV-1 replicon may facilitate studies on viral replication and antiviral
      compound discovery. 

PMID- 24858612
TI  - Acute encephalopathy associated with human metapneumovirus infection.
AB  - We encountered a 3.5-year-old girl with acute encephalopathy associated with
      human metapneumovirus (hMPV) infection. She had pyrexia and status epilepticus,
      followed by a coma. Cerebrospinal fluid analysis showed no pleocytosis or
      elevation of protein levels. hMPV RNA was detected in tracheal aspirate. Acute
      encephalopathy in the patient was probably related to the hMPV infection. Serum
      levels of interleukin-6 and matrix metalloproteinase-9 were elevated on
      admission, and these factors were presumed to be related to acute encephalopathy,
      associated with her viral infection, or due to status epilepticus. She was
      treated with dexamethasone pulse therapy, intravenous immunoglobulin, and
      continuous thiopental infusion. She recovered without neurological sequelae. 

PMID- 24858613
TI  - Longitudinal study on respiratory viral co-infections in the presence or absence
      of clinical manifestation in infants aged 0-2 years.
AB  - We conducted a long-term follow-up study between December 2005 and February 2007
      on 4 immunocompetent infants, who repeatedly presented with respiratory symptoms,
      using PCR-based techniques targeting 14 viruses related to acute respiratory
      tract infection. Of 38 specimens, 30 were collected from symptomatic infants and
      8 were collected when respiratory symptoms were absent. Overall, one or more
      respiratory viruses were detected in 94.7% (36/38) of the specimens. Of the 36
      PCR-positive specimens, 77.8% (28/36) were positive for more than one virus. Most
      of these co-infections were double infections (55.6% or 20/36). Of note, co
      infections with 4 and 3 viruses were observed in 3 (8.3% or 3/36) and 5 (13.9% or
      5/36) specimens, respectively. Of the 8 specimens collected from the 4 infants
      when apparent respiratory symptoms were absent, 7 (87.5%) were positive for
      respiratory viruses. Respiratory viral co-infections were also frequent and found
      in 5 of the specimens (62.5%). However, apparent correlation between disease
      severity and co-infection was undetectable due to the limit of the number of
      cases studied. Taken together, this longitudinal study revealed that respiratory
      viral co-infections were not infrequent in infants aged 0-2 years, regardless of
      the presence of respiratory symptoms (62.5-77.8%). 

PMID- 24858615
TI  - Phylogenetic analysis of dengue virus type 3 strains primarily isolated in 2013
      from Surabaya, Indonesia.

PMID- 24858614
TI  - Outbreak of cholera caused by Vibrio cholerae O1 El Tor variant strain in Bihar,
      India.
AB  - An outbreak of cholera struck Bihar, an Indian state, in August 2008 following a
      massive flood. Here we report the phenotypic and genotypic characteristics of
      Vibrio cholerae strains isolated from patients with diarrhea. Rectal swabs were
      obtained from patients with diarrhea who were admitted to medical camps or the
      hospital, and the strains were biochemically and serologically characterized. V.
      cholerae was isolated from 21 (65.6%) of 32 rectal swabs. Serological studies
      revealed that all the 21 isolates belonged to V. cholerae O1 Ogawa. Mismatch
      amplification mutation assay (MAMA)-PCR showed that the isolates belonged to El
      Tor variant group, and pulsed-field gel electrophoresis (PFGE) proved that these
      isolates were of a different lineage than the conventional El Tor variant
      strains. These isolates were resistant to several drugs, including ampicillin,
      streptomycin, tetracycline, nalidixic acid, and furazolidone. The uniqueness of
      the current report arises from the fact that records of cholera in Bihar are
      availiable for the early 1960s but not for the next 4 decades. Moreover, the
      present study is the first to report a cholera outbreak in Bihar that was caused
      by an El Tor variant strain. 

PMID- 24858616
TI  - Burden of pertussis is underestimated in South Korea: a result from an active
      sentinel surveillance system.

PMID- 24858617
TI  - Intra-abdominal Mycoplasma hominis infection in a liver transplant recipient: a
      case report.

PMID- 24858618
TI  - Ameliorative potential of aliskiren in experimental colitis in mice.
AB  - In the present study, we investigated the ameliorative potential of aliskiren in
      dextran sulfate sodium (DSS) induced colitis in mice. Aliskiren (3 and 10mg/kg,
      i.p.) was administered for 10 days from the day of DSS administration. The
      severity of colitis in mice was assessed using body weight loss, colon and spleen
      weight, hematological parameters, food intake, stool consistency, rectal bleeding
      and colon shortening. Colonic malondialdehyde (MDA), myeloperoxidase (MPO) and
      renin mRNA levels were also estimated. Furthermore, TNF-alpha and IL-6 in plasma
      and colon were analyzed. The results showed that aliskiren (10mg/kg, i.p.)
      significantly improved the severity of colitis by, decrease in weight loss,
      improvement in food intake and stool consistency, decrease in rectal bleeding,
      decrease in relative colon and spleen weight and improvement in colonic
      shortening. Aliskiren (10mg/kg, i.p.) improved blood hemoglobin, red blood cells
      (RBC) and hematocrit. Colonic malondialdehyde (MDA), MPO and histolopathological
      score were significantly diminished by aliskiren (10mg/kg, i.p.). Furthermore,
      aliskiren (10mg/kg, i.p.) significantly diminished the elevated levels of TNF
      alpha, IL-6 and renin mRNA in inflammed colon. These results indicate involvement
      of renin in colitis and inhibition of renin by aliskiren ameliorates colitis. 

PMID- 24858619
TI  - PPAR-gamma inhibits IL-13-induced collagen production in mouse airway
      fibroblasts.
AB  - Interleukin-13 (IL-13) plays an important role in extracellular matrix production
      of airway remodeling in asthma. Activation of PPAR-gamma has been shown to
      inhibit the occurrence of airway fibrosis in asthma, yet it remains unknown
      whether the effect of PPAR-gamma on suppression of airway fibrosis is associated
      with the inhibition of IL-13 signaling. In the present study, primary cultured
      airway fibroblasts were stimulated with IL-13, and JAK inhibitor, PDGF receptor
      blocker and MEK inhibitor were applied to investigate the involvement of these
      pathways in IL-13-induced collagen production. Our results demonstrate that IL-13
      dose- and time-dependently induced collagen production in primary cultured mouse
      airway fibroblasts; this effect was blocked by inhibition of JAK/STAT6 signal
      pathway. IL-13 also stimulated JAK/STAT6-dependent PDGF production, elevation of
      PDGF in turn activated ERK1/2 MAPK and caused collagen production. Activation of
      PPAR-gamma by rosiglitazone reduced IL-13-induced collagen expression by
      suppression of STAT6-driven PDGF production. Our results indicate that activation
      of JAK/STAT6 signal and subsequent PDGF generation and ERK1/2 MAPK activation
      mediate IL-13-induced collagen production in airway fibroblasts. This study
      suggests that activation of PPAR-gamma might be a novel strategy for the
      treatment of asthma partially by inhibition of airway fibrosis. 

PMID- 24858621
TI  - Evaluation of Jagged2 and Gli1 expression and their correlation with prognosis in
      human hepatocellular carcinoma.
AB  - Jagged2 is closely associated with numerous congenital diseases and has an
      important role in multiple malignancies. It has been identified that Jagged2 is a
      sonic hedgehog-regulated factor. However, its expression and correlation with
      Gli1 in hepatocellular carcinoma (HCC) remain unknown. A total of 58 samples of
      surgically resected paired HCC and normal tumor-adjacent tissues were collected,
      and the Jagged2 and Gli1 expression was detected in the samples using
      immunohistochemical staining. The correlation between Jagged2 and Gli1 protein
      expression, and their correlation with the clinicopathological features of HCC
      were analyzed. The protein expression of Jagged2 and Gli1 were significantly
      upregulated in HCC tissues compared with the normal tumor-adjacent tissues
      (P<0.001, respectively), and Jagged2 expression was positively correlated with
      Gli1 protein in HCC tissues (r=0.643, P<0.001). Jagged2 and Gli1 protein were
      expressed at significantly higher levels in patients with intrahepatic
      metastasis, high histological grade and advanced tumor-node-metastasis stage
      (TNM) stage (P<0.05, respectively). With the Cox proportional hazard regression
      mode, the independent factors predictive of poor long-term HCC survival following
      radical liver resection included high expression of Jagged2, advanced TNM stage
      and high histological grade (P<0.05). In HCC, high expression of Jagged2 was
      closely correlated with poor clinicopathological features, and it may therefore
      be a potential prognosis predictor for patients with HCC. 

PMID- 24858620
TI  - Characterization of the intrinsic activity for a novel class of cannabinoid
      receptor ligands: Indole quinuclidine analogs.
AB  - Our laboratory recently reported that a group of novel indole quinuclidine
      analogs bind with nanomolar affinity to cannabinoid type-1 and type-2 receptors.
      This study characterized the intrinsic activity of these compounds by determining
      whether they exhibit agonist, antagonist, or inverse agonist activity at
      cannabinoid type-1 and/or type-2 receptors. Cannabinoid receptors activate Gi/Go
      proteins that then proceed to inhibit activity of the downstream intracellular
      effector adenylyl cyclase. Therefore, intrinsic activity was quantified by
      measuring the ability of compounds to modulate levels of intracellular cAMP in
      intact cells. Concerning cannabinoid type-1 receptors endogenously expressed in
      Neuro2A cells, a single analog exhibited agonist activity, while eight acted as
      neutral antagonists and two possessed inverse agonist activity. For cannabinoid
      type-2 receptors stably expressed in CHO cells, all but two analogs acted as
      agonists; these two exceptions exhibited inverse agonist activity. Confirming
      specificity at cannabinoid type-1 receptors, modulation of adenylyl cyclase
      activity by all proposed agonists and inverse agonists was blocked by co
      incubation with the neutral cannabinoid type-1 antagonist O-2050. All proposed
      cannabinoid type-1 receptor antagonists attenuated adenylyl cyclase modulation by
      cannabinoid agonist CP-55,940. Specificity at cannabinoid type-2 receptors was
      confirmed by failure of all compounds to modulate adenylyl cyclase activity in
      CHO cells devoid of cannabinoid type-2 receptors. Further characterization of
      select analogs demonstrated concentration-dependent modulation of adenylyl
      cyclase activity with potencies similar to their respective affinities for
      cannabinoid receptors. Therefore, indole quinuclidines are a novel structural
      class of compounds exhibiting high affinity and a range of intrinsic activity at
      cannabinoid type-1 and type-2 receptors. 

PMID- 24858622
TI  - The prognostic value of left ventricular mechanical dyssynchrony using gated
      myocardial perfusion imaging in patients with end-stage renal disease.
AB  - BACKGROUND: Prior studies show that left ventricular mechanical dyssynchrony
      (LVD), measured by gated SPECT myocardial perfusion imaging (MPI), identifies
      patients with end-stage renal disease (ESRD) at higher risk for all-cause
      mortality but these were in small number of patients. We sought to assess the
      interaction between LVD and LV perfusion pattern in risk-stratification of a
      large sample size of patients with ESRD. METHODS: From the renal transplantation
      database maintained at the University of Alabama at Birmingham, we identified
      consecutive patients with ESRD who had gated SPECT MPI between 2003 and 2007.
      MPIs were reprocessed to derive LV ejection fraction (EF), perfusion defect size,
      and LVD [phase bandwidth (BW) and phase standard deviation (SD)]. The primary end
      point was all-cause mortality, which was prospectively collected and verified
      against the social security death index database. RESULTS: There were 828
      patients aged 52.6 +/- 0.36 years (45% were women and 60% had diabetes mellitus).
      The LVEF was 54.8 +/- 0.4% and the perfusion pattern was abnormal in 334 patients
      (41%). During a follow-up period of 61 +/- 0.9 months, 230 patients (28%)
      received renal transplants and 290 patients (35%) died. The phase BW (73.1 +/-
      2.6 degrees  vs 66.3 +/- 1.8 degrees , P = .02) and SD (25.2 +/- 0.8 degrees  vs
      23.4 +/- 0.5 degrees , P = .06) were greater in patients who died than those who
      survived indicating greater dyssynchrony. Patients with phase BW >56 degrees  or
      SD >=21 degrees  (median values) had worse 5-year survival (64% vs 72%, and 66%
      vs 71%, log-rank P = .005 and P = .07, respectively). After adjusting for
      demographics, co-morbidities, LVEF, and perfusion pattern, phase BW was
      associated with worse outcome (hazard ratio 1.289 95% CI 1.010-1.644, P = .04).
      CONCLUSIONS: LVD by phase analysis of gated SPECT MPI provides prognostic value
      in ESRD beyond myocardial perfusion and EF.

PMID- 24858623
TI  - Risk stratification by quantitation of LV dyssynchrony: a new branch of the field
      of nuclear cardiology.

PMID- 24858624
TI  - Evaluation of inflamed coronary atherosclerotic plaques by PET: more evidences
      for a promising area of cardiovascular imaging.

PMID- 24858625
TI  - I-123 mIBG and Tc-99m myocardial SPECT imaging to predict inducibility of
      ventricular arrhythmia on electrophysiology testing: a retrospective analysis.
AB  - OBJECTIVES: The purpose of this study is to assess mIBG uptake in scar border
      zone and its relation with ventricular arrhythmia (VA) inducibility on
      electrophysiology (EP) testing using I-123 mIBG SPECT and resting Tc-99m SPECT
      myocardial perfusion imaging (MPI). METHODS: Forty-seven patients from a previous
      clinical trial were retrospectively analyzed. These patients underwent I-123 mIBG
      and resting Tc-99m tetrofosmin SPECT, and EP testing. Twenty-eight patients were
      positive (EP+) and 19 patients were negative (EP-) for inducibility of sustained
      (>30 seconds) VA on EP testing. MPI scar extent, border zone extent, and mIBG
      uptake in border zone were used to predict VA inducibility on EP testing,
      respectively. RESULTS: There was no significant difference in scar extent between
      the EP+ and EP- groups. The EP+ group had significantly larger border zone and
      lower mIBG uptake ratio in the border zone than the EP- group. Receiver operating
      characteristic (ROC) curve analysis showed that the prediction accuracy for
      border zone extent (area under ROC = 0.75) was better than scar extent (area
      under ROC = 0.66). The prediction accuracy was further improved (area under ROC =
      0.78), when assessing mIBG uptake in the border zone. CONCLUSION: A new tool has
      been developed to measure scar and border zone and to assess mIBG uptake in scar
      and border zone from combined I-123 MIBG SPECT and resting Tc-99m SPECT MPI. The
      mIBG uptake in the border zone predicted VA inducibility on EP testing with a
      promising accuracy.

PMID- 24858627
TI  - Pro: endoscopic endonasal transsphenoidal pituitary surgery is superior to
      microscope-based transsphenoidal surgery.
AB  - The introduction of the endoscope to transsphenoidal pituitary surgery is
      relatively new, but represents a major advancement in the field. The use of the
      endoscope to visualize the sella via a direct endonasal approach offers the
      surgeon dramatically better visualization as well as improved range of motion
      compared to the operating microscope. Growing evidence confirms that these
      improvements directly translate into better surgical resections and outcomes.
      Further, patient comfort and satisfaction are higher with the endonasal method
      compared with other transsphenoidal approaches, and it is a cost effective
      technology. This position paper will outline the reasons that endoscopic
      endonasal transsphenoidal surgery is the preferred method for pituitary surgery,
      and why it will likely be adopted as the standard technique for transsphenoidal
      surgery worldwide. 

PMID- 24858629
TI  - Analysis and clinical correlates of 20 Hz photic driving on routine EEG in
      migraine.
AB  - Enhanced photic driving (PD) during high-frequency flicker stimulation, the so
      called H response, is a classical feature of migraine patients between attacks,
      but is thought to be of poor clinical utility. Visual inspection of the EEG for
      its detection may not be reliable, however, data on its possible correlations
      with clinical features and migraine pathophysiology are scarce. We have compared
      visual inspection and EEG spectral analysis to detect abnormal PD in 280
      consecutive migraine patients of our headache clinic (episodic migraine without
      aura, n = 171; chronic migraine, n = 48; migraine with aura, n = 61) and in a
      group of 24 non-migrainous neurological controls. Spectral frequency analyses
      were performed blindly by one of us (YF). On visual inspection, 50.4 % of
      migraineurs were thought to have increased 20 Hz PD. After spectral analysis,
      only 62.4 % of them had PD power superior to the mean + 95 % CI of the control
      group. Sensitivity of visually identified PD was 82.24 %, specificity 69.36 %.
      Increased PD on spectral analysis was more prevalent in episodic migraine than in
      chronic migraine, in patients with low attack frequency, in those with ictal
      autonomic symptoms in addition to nausea and in those with a strong family
      history of migraine. We confirm therefore that 20 Hz photic driving is of little
      diagnostic utility and its prevalence in migraine overestimated on visual
      inspection. Its presence on spectral analysis of the EEG, however, might be of
      pathophysiological interest, as it identifies subgroups of migraineurs of whom
      the common denominator could be lack of habituation of cortical responses during
      repetitive stimulation.

PMID- 24858628
TI  - Perioperative kinetics of parathyroid hormone in unilateral, primary thyroid
      surgery.
AB  - Dysfunction of the parathyroid glands is an important cause of complications
      after thyroid surgery. Intraoperative monitoring of the function of the
      parathyroid glands can be performed using parathyroid hormone (PTH) kinetics.
      Unilateral thyroid surgery is associated with a decreased risk for postoperative
      hypocalcemia (POH) and permanent hypoparathyroidism (PEH). We focused on
      unilateral thyroid surgery by monitoring the functionality of the parathyroid
      glands and comparing the perioperative PTH kinetics of patients with and without
      POH. In a prospective study, 143 patients scheduled for unilateral thyroid
      surgery underwent monitoring of perioperative changes in serum PTH and serum
      calcium levels, and of clinical symptoms of hypocalcemia. The rates of POH and
      PEH were 18.2 and 0%, respectively. In patients without POH, PTH significantly
      increased from the time of skin incision to the end of the operation and after
      the operation (20.1 pg/ml, IQR 15.5-26.8 vs. 21.4 pg/ml, IQR 16.4-29.5; p=0.005),
      which was not the case in patients who developed POH. In a multivariate analysis
      of predictive factors for POH, two parameters became significant, namely female
      gender (odds ratio 6.87, 95% confidence interval 0.92-51.01) and lower initial
      serum calcium levels (odds ratio 3.54*e(-8), 95% confidence interval 3.63*e(-12);
      0.00). The rate of POH was unexpectedly high. Rather than intraoperative PTH
      declines, an unstable balance of factors that influence calcium metabolism likely
      is the major contributor to POH after unilateral thyroid surgery. There was no
      case of PEH after unilateral, primary thyroid surgery, which underlines the need
      for an individualized approach to the extent of resection.

PMID- 24858630
TI  - Metacognitive change as a predictor of outcome in cognitive therapy for
      psychosis.
AB  - BACKGROUND: There is little known about predictors of response to cognitive
      therapy (CT) for psychosis. This study tests the hypothesis that metacognitive
      change at both end of treatment and follow-up is associated with positive
      outcomes in people with psychosis receiving CT. METHOD: Patients referred for CT
      for psychosis were offered CT over a maximum of 30 sessions. Assessments,
      including interview-based measures of psychotic symptoms and a questionnaire
      assessing metacognitive worry, were performed at pre-CT, post-CT and one-year
      follow-up. Data from 32 patients were analyzed. RESULTS: Significant positive
      relationships were found between metacognitive worry change scores at one-year
      follow-up and both positive symptoms of psychosis and particular dimensions of
      hallucinations. No significant relationships were found between metacognitive
      change and delusional symptoms. CONCLUSIONS: These results suggest that
      metacognitive change is associated with symptom change at followup. In
      particular, these benefits seem most evident in those people experiencing
      hallucinations. Methodological limitations and clinical implications are
      discussed.

PMID- 24858631
TI  - Mentalization-based treatment for psychosis: linking an attachment-based model to
      the psychotherapy for impaired mental state understanding in people with
      psychotic disorders.
AB  - Disturbances of mentalization have been increasingly associated with the symptoms
      and functional impairment of people with psychotic disorders. it has been
      proposed that psychotherapy designed to foster self and other understanding, such
      as mentalization-based treatment (mBt), may play an important part in
      facilitating recovery from psychosis. Here, we present an attachment-based
      understanding of mentalization impairments. We then outline a neuropsychological
      model that links disruptions of mentalization associated with disturbances in the
      caregiving environment to the pathophysiology of psychosis in genetically at-risk
      individuals. this is followed by an illustration of some of the core mBt
      techniques for the rehabilitation of the capacity to mentalize as applied to the
      treatment of a patient with a psychotic disorder. 

PMID- 24858632
TI  - Chronic persecutory delusion and autobiographical memories in patients with
      schizophrenia: a diary study.
AB  - BACKGROUND: While chronic persecutory delusions are typically anchored into
      patients' everyday life situations, no investigation has ever looked at how
      situations associated with a feeling of persecution are recorded and later
      retrieved. METHOD: a diary methodology combined with a recognition task involving
      ten patients with schizophrenia who presented chronic persecutory delusions and
      ten control participants. Diaries of everyday persecutory events (Pe) and non
      persecutory events (nPe) were kept. RESULTS: in both groups, 1) Pe were
      associated with higher anxiety scores than nPe, 2) Pe were experienced as less
      distinctive and more stereotyped than nPe, 3) the frequency of incorrect
      recognition of altered descriptions of Pe was higher than that of nPe.
      LIMITATIONS: because high levels of motivation are required of the diarists, our
      sample size was small. CONCLUSION: Memories of persecutory events were highly
      emotional and semanticized. they were frequently incorrectly recognized,
      suggesting the existence of bias resulting from interactions between their
      processing and persecutory delusions.

PMID- 24858633
TI  - Metacognition in non-psychotic help-seeking adolescents: associations with
      prodromal symptoms, distress and psychosocial deterioration.
AB  - OBJECTIVE: To explore the notion that difficulties in metacognitive functioning
      are a core pre-psychotic feature of emerging schizophrenia and its spectrum.
      METHOD: Seventy-eight help-seeking, non-psychotic adolescents (age 13-18) were
      assessed with the Prodromal Questionnaire (PQ), the Structured Interview for
      Prodromal Syndromes (SIPS), two scales of social and role functioning, and a
      metacognitive version of two non-social (verbal memory and executive functioning)
      and two social (facial emotion perception and Theory of Mind) cognition tasks. In
      addition to the standard administration of the tasks, subjects were also asked to
      rate their level of confidence in the correctness of each answer, and to choose
      whether they wanted it to be "counted" toward their overall performance score on
      the task. Each "volunteered" response received a bonus of 5 cents if correct, but
      an equal penalty if wrong. RESULTS: Levels of cognitive and metacognitive
      functioning were not significantly different between subjects at high versus low
      risk. However, the prediction of psychosocial functioning reached significance
      when adding the novel metacognitive measures to the conventional measures of
      cognitive and social-cognitive abilities. DISCUSSION: These results challenge the
      robustness of the link between neurocognitive deficits and risk for
      schizophrenia. However, they suggest that metacognition plays an important
      moderating role in the association between neurocognition and functional outcome
      before acute onset of the illness.

PMID- 24858634
TI  - Metacognition in schizophrenia and schizotypy: relation to symptoms of
      schizophrenia, traits of schizotypy and Social Quality of Life.
AB  - OBJECTIVE: The current study examined a mediation model in which symptoms of
      schizophrenia and schizotypy traits mediate the positive relations between
      metacognition and Social Quality of Life (SQoL) among persons with schizophrenia
      and persons without mental illness. METHOD: 39 persons diagnosed with
      schizophrenia and 60 persons without a severe mental illness diagnosis
      participated in this study. Instruments included the Metacognition Assessment
      Scale-Abbreviated (MAS-A), the SQoL scale of the QLI-MH, the PANSS scale and the
      O-LIFE self-report questionnaire that assesses schizotypy traits. RESULTS:
      Persons with schizophrenia exhibit lower SQoL and metacognitive abilities than
      persons without mental illness. For persons with schizophrenia, negative symptoms
      mediate the positive relation between the ability to understand other persons'
      minds and SQoL. However, although for persons without mental illness,
      understanding other minds was found to correlate negatively with introvertive
      anhedonia and SQoL, a mediation model was not confirmed. DISCUSSION:
      Understanding of others' minds seems relevant to the SQoL for both samples. In
      addition, negative symptoms of schizophrenia and introvertive anedonia traits are
      also related to SQoL among persons with schizophrenia and among persons without
      mental illness respectively. The lack of support for a mediation model for
      persons without mental illness is consistent with the theories that claim
      schizotypy is not a mirror image of schizophrenia and, therefore, may not
      necessarily lead to schizophrenia. Limitations of this study and suggestions for
      future research are discussed.

PMID- 24858635
TI  - Metacognition in schizophrenia spectrum disorders: methods of assessment and
      associations with neurocognition, symptoms, cognitive style and function.
AB  - Deficits in metacognitive capacity in schizophrenia can be conceptualized as
      existing along a spectrum from more discrete to more synthetic activities. While
      each represents an equally important focus of study, synthetic metacognitive
      activities may be more difficult to measure given they are more a matter of
      assessing complexity of thought rather than concrete accuracy; and therefore have
      received less attention. This review summarizes research on synthetic
      metacognition using a paradigm in which metacognitive capacity is rated within
      personal narratives. Results across the work reviewed here provides evidence that
      these deficits are detectable in patients with schizophrenia and that deficits
      are related to, but not reducible to, symptom severity and poorer neurocognitive
      function. Independent of symptoms and neurocognition, deficits in synthetic
      metacognition are related to a range of mental activities including reasoning
      style, learning potential and insight. These deficits may also play a role in
      long term outcome via their impact on the ability to function in work settings
      and to think about and sustain social connections. 

PMID- 24858636
TI  - Metacognition in schizophrenia: a concept coming of age.
AB  - The concept of metacognition in the context of schizophrenia has recently
      received increasing attention in clinical psychology and psychiatry. impaired
      metacognitive abilities in patients with schizophrenia have been associated with
      symptomatology, cognition, social functioning and quality of life. in this series
      of articles published as a Special issue of the israel Journal of Psychiatry,
      edited by Paul H. Lysaker and ilanit Hasson-Ohayon, several new possible
      ramifications of metacognition with regard to persistence of symptoms, treatment
      issues and early recognition of schizophrenia are presented, in addition to
      corroborations of previous findings relating to the aetiology of impaired
      metacognition and outcome measures. the present invited commentary focuses on
      potential implications for a more individualized therapeutic approach to
      schizophrenia, early detection of at-risk states, and ways to link metacognition
      with neuroscientific approaches.

PMID- 24858637
TI  - Reliability and cross-validation of the Night Eating Questionnaire (NEQ): Hebrew
      version.
AB  - BACKGROUND: Several developments in diagnosing night eating syndrome (NES)
      occurred during the last decade. New proposed diagnostic criteria are now
      available, and a short Night Eating Questionnaire (NEQ) was published. The study
      aims were to validate the NEQ for assessing NES, to identify the optimal NEQ cut
      point for NES diagnosis, and to validate and test the internal reliability of the
      translated Hebrew version of the NEQ. METHOD: 141 participants completed the
      questionnaire and a diagnostic interview, divided into four groups: NES (n=59),
      Partial diagnosis PD-NES (n=42), other eating disorders (n=8) and controls (32).
      Validity was measured by calculating reliability, factor structure, and comparing
      the interview diagnosis to the NEQ score using different cut scores. RESULTS:
      Cronbach's alpha was 0.78, and principal components analysis yielded a five
      factor structure. A cut score of 21 provided the best balance of false and true
      positive diagnosis. CONCLUSIONS: We concluded that the NEQ may be an acceptable
      screening instrument for assessing NES symptomatology.

PMID- 24858639
TI  - Biofilm formation in Acinetobacter baumannii.
AB  - Acinetobacter baumannii has received much attention in recent years because of
      its increasing involvement in a number of severe infections and outbreaks
      occurring in clinical settings, and presumably related to its ability to survive
      and persist in hospital environments. The treatment of infections caused by A.
      baumannii nosocomial strains has become increasingly problematic, due to their
      intrinsic and/or acquired resistance to multiple classes of antibiotics.
      Furthermore, the demonstrated ability of nosocomial strains to grow as biofilm is
      believed to play a significant role in their persistence and antibiotic
      resistance. This review summarises current knowledge on A. baumannii biofilm
      formation and its clinical significance, as well as the related genetic
      determinants and the regulation of this process. 

PMID- 24858638
TI  - PmMGST3, a novel microsomal glutathione S-transferase gene in the dinoflagellate
      Prorocentrum minimum, is a potential biomarker of oxidative stress.
AB  - In this study, we evaluated a novel microsomal glutathione S-transferase3 (MGST3)
      gene from the dinoflagellate Prorocentrum minimum, and examined its expression
      pattern in response to copper-and nickel-induced stresses. The full length of
      PmMGST3 was 732 bp, ranging from the dinoflagellate splice leader (DinoSL)
      sequence to the poly (A) tail, covering a 441-bp ORF, 97-bp 5'UTR, and 194-bp
      3'UTR. The PmMGST3 was up-regulated by metals, including copper and nickel. The
      highest up-regulation levels of the PmMGST3 were found under 0.1 mg/L copper and
      0.5 mg/L nickel treatment, respectively. In addition, the PmMGST3 was gradually
      up-regulated by 0.1 mg/L copper with increasing exposure time. Furthermore, ROS
      production and reduced GSH was measured in the copper treated cells. A
      significant increased ROS production and reduced GSH were found in the copper
      treated cells. These results suggest that PmMGST3 may be related to defense
      mechanisms associated with oxidative stress in dinoflagellates.

PMID- 24858640
TI  - Differential expression of HER2, STAT3, SOX2, IFI16 and cell cycle markers during
      HPV-related head and neck carcinogenesis.
AB  - The aim of this study was to analyze protein and gene expression of HER2 in 224
      head and neck precancerous and malignant lesions by immunohistochemistry and FISH
      analysis. In parallel, expression of pStat3, Sox2, IFI16 and p16, Ki67 was
      evaluated. Immunohistochemical analysis was assessed on formalin-fixed paraffin
      embedded (FFPE) tissue specimens. A combined method for HPV detection consisting
      of p16 immunostaining and two PCR probes was applied. HER2 gene status was
      evaluated by FISH analysis. HPV DNA was detected in 24% of cases with predominant
      HPV16 genotype. HPV-positive lesions had higher HER2, pStat3 and within carcinoma
      group, and higher IFI16 expression compared to the HPV-negative group (Fig. 1A-B
      C). A strong positive correlation between Sox2 and proliferative activity was
      observed, whereas IFI16 expression displayed a negative relationship with Sox2
      and Ki67 activity. The most striking result was higher pStat3 expression in HPV
      positive lesions and its strong positive correlation with IFI16 expression. The
      presence of HPV may induce upregulation of HER2/neu, pStat3 and IFI16. High
      levels and a strong positive correlation between pStat3 and IFI16 suggest their
      synergistic pro-apoptotic effects in HPV-positive lesions. 

PMID- 24858641
TI  - Four-year outcome of a PI and NRTI-sparing salvage regimen: maraviroc,
      raltegravir, etravirine.
AB  - Aim of this study was to report the 204-week efficacy and safety results of a
      novel PI- and NRTI-sparing regimen for salvage therapy including maraviroc,
      raltegravir, etravirine in 28 failing HIV-infected patients with R5-tropic virus.
      The trend of laboratory parameters was tested by ANOVA for repeated measures and
      Greenhouse-Geisser probabilities were reported. Results were described as median
      (Q1-Q3) values. Twenty-six (93%) out of 28 patients completed 204 weeks of
      treatment. Virological success (HIV-RNA<50 copies/mL) at week 204 was 96%. CD4+
      counts significantly increased [244 (158-213) cells/mm3, p<0.0001] from baseline
      [247 (68-355) cells/mm(3)] as well as CD4+ percentage. Four serious adverse
      events (1 death due to Hodgkins's lymphoma, 1 anal cancer, 1 Hodgkins's lymphoma,
      1 recurrence of mycobacterial spondylodiscitis) were observed; three events led
      to transitory discontinuation of the antiretroviral therapy due to drug-drug
      interaction. BMI (p<0.0001) and waist circumference (p<0.0001) significantly
      increased over 204 weeks. An amelioration was also observed in relation to
      haemoglobin (p=0.0006), platelets (p<0.0001), white blood cell (p=0.013),
      neutrophils (p=0.301), lymphocytes (p=0.207) and creatinine (p<0.0001). In highly
      treatment-experienced patients the maraviroc, raltegravir and etravirine
      combination is associated with a good long-term efficacy and safety profile.

PMID- 24858642
TI  - Interferon-gamma release assay in HIV-infected patients with active tuberculosis:
      impact of antituberculous drugs on host immune response.
AB  - The objective of the study was to: 1) investigate the performance of QuantiFERON
      TB Gold In-Tube (QFT-GIT) in HIV-infected patients with active tuberculosis (TB);
      2) evaluate the sequential changes in QFT-GIT assay during the treatment
      response; 3) investigate the direct in vitro effects of antituberculous drugs on
      both secretion of IFN-g and apoptosis of T cells. Forty-four HIV-patients with
      active TB were enrolled and tested with QFT-GIT. Thirteen of them were followed
      longitudinally by QFT-GIT, performed at baseline and six and nine months after TB
      treatment onset. For in vitro experiments, cells from healthy donors and HIV
      naive subjects were pretreated with four antituberculous-drugs, and then examined
      for IFN-g secretion and apoptosis of T-cells. The QFT-GIT was positive in 66%,
      negative in 11.3% and indeterminate in 22.7%. Longitudinal analysis in 13 HIV-TB
      subjects showed that at therapy completion a reversion to negative response was
      found only in 38.4% of patients, but in 30.7% the QFT-GIT remained positive.
      Overall, during the anti-TB treatment no significant decrease in average IFN-g
      response was observed in these patients (p<0.001). In vitro experiments showed
      that the four antituberculous- drugs, within the range of therapeutically
      achievable concentrations, did not exert any down-regulatory effect on IFN-g
      production and did not have any effect on apoptosis of T cells from HIV naive
      subjects. Despite the high rate of indeterminate results, QFT-GIT assay may
      represent a good tool in the diagnostic workup for active TB in HIV-patients.
      Although the antituberculous drugs do not have any direct effect on host immune
      response to mycobacterial antigen, changes in longitudinal IGRA response have
      been found during in vivo anti-TB treatment. 

PMID- 24858643
TI  - Less drug regimens and PI/r-based strategies in HIV infection: focus on best
      practices using the HIV patient's journey methodology.
AB  - During these last two years less drug regimens (LDRs) in HIV, and in particular
      protease inhibitor (PI)/r-based strategies, have been explored both in clinical
      trials and in clinical practice. Many results are now available and more is known
      about how to use them safely and effectively. Understanding that an LDR strategy
      represents a real tailored therapeutic approach for the patient is crucial for
      the long-term success and positive management of HIV infection. Trust between
      patients and HIV specialists and a real focus on the patient's life are key
      factors for long life treatment success, in particular when using a LDR strategy.
      This is clearly shown by the HIV patient's journey (HPJ) methodology, used in an
      Italian national workshop to better define the criteria and challenges of LDR
      strategies. This paper shows the results of this complex process. 

PMID- 24858644
TI  - Emergence of carbapenem-resistant Klebsiella Pneumoniae strains producing KPC-3
      in Brescia Hospital, Italy.
AB  - Carbapenem-resistant K. pneumoniae has recently been reported as a new multidrug
      resistant nosocomial pathogen. This study reports the emergence of carbapenem
      resistant K. pneumoniae strains in Brescia Civic Hospital, Italy. Different
      samples, collected from April 2012 to February 2013, showed that 29 patients
      presented infections from multidrug-resistant K. pneumoniae and three of these
      patients were intestinal carriers. In total, 40 carbapenem-resistant K.
      pneumoniae strains were isolated from multiple specimens of these patients. In 39
      out of 40 samples, we identified the bla(KPC-3) carbapenemase gene variant
      responsible for bacterial carbapenem resistance. The DiversiLab analysis showed
      four different genetic patterns within multidrug-resistant K. pneumoniae
      isolates, with pattern 1 and 2 including 95% of the bacterial strains. Carbapenem
      resistant K. pneumoniae strains belonging to patterns 1 and 2 were also detected
      in the intestinal tract of the three asymptomatic carriers. Moreover, isolation
      of the same strains in other body sites of the same patients and in bronchial
      fluid of a non-colonized patient in the same ward indicates an initial
      dissemination of this pathogen. Our results highlight the emergence of
      carbapenemase-producing K. pneumoniae strains in different hospital wards and the
      urgent need for infection control, antibiotic stewardship programmes and
      utilization of a surveillance and prevention system.

PMID- 24858645
TI  - Outbreak of multidrug-resistant Acinetobacter baumannii in an intensive care
      unit.
AB  - Acinetobacter baumannii is a ubiquitous microrganism often able to colonize and
      survive in different environments. Currently it is one of the most common
      pathogens responsible for nosocomial infections, including outbreaks, especially
      in long-term care facilities. The aim of this study was to show the results of an
      environmental investigation and genotyping analysis of multidrug-resistant
      Acinetobacter baumannii associated with an outbreak in an intensive care unit of
      a tertiary hospital located in Northern Sardinia, Italy. Positive cultures of MDR
      Acinetobacter baumannii were reported during the month of June 2012, after the
      collection of biological samples from ten patients. Acinetobacter baumannii was
      isolated during the following environmental investigation from the headboard of
      two beds. All the strains were genotyped by performing multiplex PCR to identify
      the presence of genes encoding carbapenemases. The results showed specific bands
      of bla(OXA-51-like) gene and of the bla(OXA-23-like) gene. PFGE highlighted
      minimal differences in genomic fingerprints, while the cluster analysis grouped
      the isolated microorganisms into two closely related clusters, characterized by
      Dice's similarity coefficient equal to 95.1%. MLST showed that the strains
      belonged to ST31. The results of the study highlight the need, especially in high
      risk areas, to adopt strict hygiene practices, particularly hand hygiene, and to
      ensure an appropriate turnover of personal protective equipment, which could be
      responsible for the spread of biological agents, such as MDR Acinetobacter
      baumannii.

PMID- 24858646
TI  - Ultra-low power laser stimulation impairs the adhesion of Staphylococcus aureus
      to primary human cells, and interferes with the expression of staphylococcal
      pathogenic factors.
AB  - Lasers are commonly used in several fields of medicine as a complementary therapy
      for internal medicine, surgery and also diagnostics. The efficacy of ultra-low
      level laser therapy (ULLLT) at power levels around 0.15 mW/cm(2) has been
      demonstrated both in in vitro experiments and in the clinical environment. This
      work used an ULLLT laser source to analyze its efficacy on Staphylococcus aureus
      adhesion to cells and on its ability to produce pathogenic factors. Laser
      stimulation succeeded in impairing the binding of S. aureus to primary human
      cells in culture and in inhibiting the expression of coagulase, one of the main
      staphylococcal pathogenic factors. The importance of the extracellular matrix
      (ECM) and the modification of the ECM redox potential in these activities were
      also evidenced.

PMID- 24858647
TI  - Development of an immunochromatographic test with anti-LipL32-coupled gold
      nanoparticles for Leptospira detection.
AB  - Detection of antibody specific to Leptospira by various immunological techniques
      has been used for leptospirosis diagnosis. However, the sensitivity of antibody
      detection during the first few days after infection is low. Molecular techniques
      are suggested to provide earlier diagnosis than antibody detection, but a rapid
      and easy to perform assay for Leptospira antigen detection would provide an
      additional useful tool for disease diagnosis. In this study, we coupled gold
      nanoparticles with antibody to LipL32, a protein commonly found in pathogenic
      Leptospira. This coupled gold reagent was used in the immunochromatographic strip
      for Leptospira detection. We demonstrated that the sensitivity of Leptospira
      detection by this strip was 10(3) ml(-1). There was no positive result detected
      when strips were tested with non-pathogenic Leptospira, Staphylococcus aureus,
      Streptococcus group B, Acinetobacter baumannii, Escherichia coli, Salmonella
      typhi, Klebsiella pneumoniae, Enterococcus faecalis or Enterococcus faecium.
      These data suggest that gold nanoparticles coupled with antibody to LipL32 could
      be used for Leptospira detection by a rapid test based on an
      immunochromatographic technique.

PMID- 24858648
TI  - Infectious prosthetic hip joint loosening: bacterial species involved in its
      aetiology and their antibiotic resistance profiles against antibiotics
      recommended for the therapy of implant-associated infections.
AB  - Reliable microbiological diagnosis along with surgery and prolonged antibiotic
      therapy are key elements in the management of prosthetic-joint infections (PJIs).
      The purpose of this study was to characterize antibiotic resistance profiles of
      bacteria involved in the aetiology of PJIs. A total of 33 bacterial isolates
      cultured from 31 patients undergoing exchange of total hip prostheses were
      analyzed. The diagnostic approach toward isolation of prosthesis- associated
      microorganisms included sonication of retrieved implants and conventional
      cultures of periprosthetic tissues and synovial fluid. The in vitro resistance
      profiles of bacterial isolates were determined in relation to antibiotics
      recommended for the therapy of PJIs using the disc diffusion method, E-tests((r))
      and broth microdilution system. Coagulase-negative staphylococci (CNS) were
      predominant microorganisms followed by Staphylococcus aureus, Enterobacter
      cloacae, Streptococcus mitis, and Propionibacterium acnes. Twenty out of 30 and
      12 out of 30 staphylococcal isolates were methicillin- and multi-drug resistant,
      respectively. Only two isolates were rifampicinresistant. All staphylococci were
      susceptible to glycopeptides and linezolid. This paper stresses the pathogenic
      role of staphylococci in patients suffering from implant loosening and reports
      high methicillin- and multidrug-resistance rates in these bacteria. Hence,
      antimicrobial susceptibility tests of individual bacterial isolates must always
      be performed to guide selection of the optimal therapeutic option.

PMID- 24858650
TI  - Extravirologic modulation of immune response by an NRTI-sparing antiretroviral
      regimen including darunavir and maraviroc.
AB  - Dual therapies, including protease inhibitor + maraviroc (MVC), may represent an
      alternative to traditional regimens for management of HIV infection. The aim of
      this in vitro study was to assess the effects of darunavir (DRV) alone or in
      combination with MVC on cell apoptosis and chemotaxis. A significant decrease of
      cell apoptosis was found after DRV treatment. The addition of MVC to DRV also had
      an in vitro down-regulating effect on cell migration. The combination of an NRTI
      sparing regimen including DRV+ MVC may have a potential role in immune system
      modulation by the direct down regulation of apoptosis and chemotaxis. 

PMID- 24858649
TI  - Evaluation of polyomavirus BK cellular immune response by an ELISpot assay and
      relation to viral replication in kidney transplant recipients.
AB  - The failure of immune surveillance may be associated with polyomavirus BK
      reactivation, potentially leading to the development of nephropathy in kidney
      transplantation. BK-specific cellular immune response may be used to modulate
      immunosuppressive therapy, but few studies have investigated the topic. Herein,
      we serially evaluated BK-specific response in 149 kidney transplant recipients
      and found that only 14/149 (9.4%) were responders. Episodes of viral reactivation
      (viremia and/or viruria) occurred only in non-responder patients. The frequency
      of BK-specific immune response appears to be lower than that for other
      persistently infecting viruses such as cytomegalovirus. 

PMID- 24858651
TI  - Screening of respiratory pathogens by Respiratory Multi Well System (MWS) r
      geneTM assay in hospitalized patients.
AB  - Novel respiratory viruses have been identified as possible agents of upper and
      lower respiratory tract infections. Multiplex real-time PCRs have been developed
      to identify clinically relevant respiratory pathogens. In this study, 178
      respiratory samples already screened for influenza virus types A and B by Flu A/B
      ASR real-time PCR kit were retrospectively analyzed with the Respiratory Multi
      Well System (MWS) r-geneTM real-time PCR kit which detects a wide spectrum of
      respiratory pathogens. The goal was to demonstrate the importance of a wide
      spectrum screening compared to a single diagnostic request. The Flu A/B ASR kit
      detected influenza B virus in 1.7% of the samples (3/178) and no influenza A
      virus. The MWS r-geneTM kit detected influenza virus in 6.7% (12/178) of samples
      (0.6% influenza A, and 6.2% influenza B), while the overall detection rate for
      respiratory pathogens was 54% (96/178). Co-infections were detected in 8/178
      (4.5%) samples. Adenovirus was the infectious agent detected most frequently,
      followed by respiratory syncytial virus. The risk of being infected by
      respiratory syncytial virus is almost threefold higher in patients older than 65
      years compared to the younger age group (OR:2.7, 95% CI: 1.2-6.2). Wide spectrum
      screening of respiratory pathogens by real-time PCR is an effective means of
      detecting clinically relevant viral pathogens. 

PMID- 24858652
TI  - Acquired echinocandin resistance in a Candida krusei blood isolate confirmed by
      mutations in the fks1 gene.
AB  - We describe a case of bloodstream infection caused by a Candida krusei strain
      that developed echinocandin resistance during caspofungin therapy. Three
      mutations were found in the HS1 region of the fks1 gene, two of them have never
      been reported either in C. krusei nor in C. albicans. 

PMID- 24858653
TI  - Allergic fungal rhinosinusitis due to Curvularia lunata.
AB  - We report a case of Curvularia lunata infection in an immunocompetent male with
      an initial diagnosis of suspected left side allergic fungal rhinosinusitis
      (AFRS), treated surgically. He had a relapse of nasal polyposis and underwent a
      surgical revision under local anaesthesia with endoscopic nasal polypectomy. The
      histological examination of the surgical specimen showed an inflammatory polyp of
      the paranasal sinuses, with eosinophil and lymphocyte infiltration, but without
      evidence of fungi. However, Curvularia spp fungus grew in cultures of nasal sinus
      drainage and bioptical specimens. The fungus was identified by DNA sequencing as
      C. lunata. The patient was then treated with itraconazole (200 mg BID for 4
      weeks), mometasone furoate nasal spray (100 mcg BID for 6 months) and normal
      saline nasal irrigations. At the last follow-up endoscopic evaluation after 19
      month from treatment, the patient was symptomless and free from disease. No polyp
      recurrence nor seromucous discharges were noticed. This first case of C. lunata
      associated AFRS reported in Italy, highlights the difficulty of this diagnosis
      and the usefulness of molecular identification of the fungal species involved. 

PMID- 24858655
TI  - Overall obesity is leveling-off while abdominal obesity continues to rise in a
      Chinese population experiencing rapid economic development: analysis of serial
      cross-sectional health survey data 2002-2010.
AB  - BACKGROUND: Obesity epidemic is related to industrialization and urbanization
      that have lead to changes in nutrition, lifestyle and socio-economic status.
      However, information on the trajectory of the obesity epidemic in populations
      experiencing rapid economic development is limited. We therefore investigate
      trends in obesity from 2002 to 2010 in a southern Chinese population experiencing
      world's fastest economic development. METHODS: Between 2002 and 2010 four
      standardized surveys were conducted in a population of 85 million residents in
      Guangdong, China. Multistage cluster sampling was adopted to recruit
      representative samples. Weight, height and waist circumference of the
      participants were measured in a standardized way. The analysis included residents
      aged between 18 and 69 years. The number of participants included in the present
      analysis for Surveys conducted in 2002, 2004, 2007 and 2010 were 13058, 7646,
      6441 and 8575, respectively. RESULTS: From year 2002 to 2010, the age
      standardized Body mass index (BMI) insignificantly changed from 21.7  kg m(-2) to
      22.3  kg m(-2), and the prevalence of overweight and overall obesity from 15.8 to
      16.6% (both P>0.05). The age-standardized waist circumference increased from 73.7
      to 78.4 cm, and prevalence of abdominal obesity increased from 12.9 to 23.7%
      (both P<0.001). In urban areas, BMI and overall obesity changed little during the
      8-year period (BMI increased from 22.6 to 22.7  kg m(-2) and overall obesity
      changed from 23.7 to 21.4%), whereas there were slight increases of the same in
      rural areas (BMI increased from 20.8 to 22.1 kg m(-2)and overall obesity
      increased from 8.2 to 13.3%). Waist circumference and abdominal obesity increased
      significantly in both areas, but the increase was more pronounced in rural areas
      (in urban area, waist circumference increased from 75.1 to 78.5 cm and abdominal
      obesity from 16.8 to 26.5%; in rural area, waist circumference from 72.2 to 78.3
      and abdominal obesity from 8.8 to 22.0%). CONCLUSIONS: BMI and overall obesity in
      this population, which has experienced the world's fastest economic development
      over the past three decades, has been leveling-off, while waist circumference and
      abdominal obesity, independent predictors of cardiovascular risk, have continued
      to rise. Our findings suggest that obesity epidemic transition in rapidly
      developing populations may be much faster than what has been observed in Western
      countries.

PMID- 24858657
TI  - Dietary nitrate supplementation improves reaction time in type 2 diabetes:
      development and application of a novel nitrate-depleted beetroot juice placebo.
AB  - BACKGROUND: In this substudy of the effect of dietary nitrate on blood pressure,
      endothelial function, and insulin sensitivity in type 2 diabetes, we report the
      development of a novel nitrate depleted beetroot juice for use clinical trials
      and determine if dietary nitrate supplementation improved cognitive function in
      patients with type 2 diabetes mellitus. METHODS: Beetroot juice was treated with
      the anion exchange resin Purolite A520e. UV-vis-spectrophotometry, and a blind
      taste test were performed along with determination of sugar content, measurement
      of ascorbate and dehydroascorbate, the ionic composition of juice and Proton NMR.
      Subsequently, 27 patients, age 67.2+/-4.9 years, (18 male) were recruited for a
      double blind, randomised, placebo-controlled crossover trial. Participants were
      randomised to begin in either order beetroot juice (nitrate content 7.5 mmol per
      250 ml) or placebo (nitrate depleted beetroot juice nitrate content 0.002 mmol
      per 250 ml). At the end of each 2 week supplementation period cognitive function
      was assessed using E-prime, E-Studio software with 5 separate tests being
      performed. The tests utilised in the present study have been adapted from the
      Cambridge Neuropsychological Test Automated Battery (CANTAB). RESULTS: The
      differences in the UV-vis spectra were comparable to the natural variation found
      in differing cultivars. There were no discernable differences in taste, sugar
      content, or Proton NMR. Ascorbate and dehydroascorbate were undetectable in
      either juice. After 2 weeks of beetroot juice simple reaction time was
      significantly quicker in the active arm at 327+/-40 ms versus 341.8+/-52.7 ms in
      the placebo arm, mean difference 13.9+/-25.6 ms (95% CI 3.8-24.0 ms), p=0.009. No
      other measures of cognitive function differed between treatment arms. CONCLUSION:
      We have developed an effective placebo beetroot juice for use in trials of
      supplementation of dietary nitrate. Two weeks supplementation of the diet with
      7.5 mmol of nitrate per day caused a significant improvement in simple reaction
      time in individuals with T2DM.

PMID- 24858656
TI  - Avoidance mediates the relationship between anxiety and depression over a decade
      later.
AB  - Anxiety and depression are often highly correlated with each other. To explain
      this connection, the present study examined the longitudinal relationship between
      earlier anxiety and later depression, using avoidance as a mediator and trauma as
      a moderator. Participants (N=6504 adolescents) completed baseline measures of
      anxiety and depression, a measure of avoidance one year later, a measure of
      trauma six to eight years later, and a measure of depression 12-14 years later.
      Analyzed with structural equation models, the results showed that anxiety
      predicted later depression, and this relationship was partially mediated by
      avoidance. The relationship between avoidance and depression was not moderated by
      trauma. Together, these findings suggest that anxiety may influence later
      depression through avoidance, and this relationship remains unaffected by
      experiencing a traumatic experience. 

PMID- 24858658
TI  - Higher CSF interleukin-6 and CSF interleukin-8 in current depression in older
      women. Results from a population-based sample.
AB  - OBJECTIVE: The literature regarding cerebrospinal fluid (CSF) cytokines in
      geriatric depression is sparse. The aim of this study was to examine associations
      between CSF interleukin-6 (IL-6), interleukin-8 (IL-8) and depression in a
      population-based sample of older women who were followed for 17 years. METHODS:
      86 dementia-free women aged 70-84 years who participated in the Prospective
      Population Study of Women in Gothenburg, Sweden took part in a lumbar puncture in
      1992-3. CSF IL-6 and CSF IL-8 were measured. Psychiatric symptoms were rated with
      the Comprehensive Psychopathological Rating Scale at baseline and at three
      subsequent face-to-face examinations. Depression (major or minor) was diagnosed
      in accordance with DSM-IV/DSM-IV research criteria. RESULTS: At baseline, women
      with ongoing major (n=10) or minor depression (n=9) had higher levels of CSF IL-6
      (p=0.008) and CSF IL-8 (p=0.007) compared with those without depression (n=67).
      Higher CSF IL-8 was related to higher MADRS score (p=0.003). New cases of
      depression were observed in 9 women during follow-ups. No associations between
      CSF cytokine levels and future depression could be shown in women without
      depression at baseline. CONCLUSION: Higher levels of CSF IL-6 and IL-8 were
      associated with current depression in this population-based sample. CSF IL-6 and
      CSF IL-8 may play a role in depression in late life.

PMID- 24858659
TI  - Evidence for increased microglial priming and macrophage recruitment in the
      dorsal anterior cingulate white matter of depressed suicides.
AB  - Despite increasing evidence supporting the neuroinflammatory theory of
      depression, little is known about cerebral macrophages in individuals suffering
      from major depression. In the present study, we investigated the morphology and
      distribution of cells immunostained for the macrophage-specific marker ionized
      calcium binding adaptor molecule 1 (IBA1) in the dorsal anterior cingulate cortex
      (dACC) white matter of middle-aged depressed suicides and matched non-psychiatric
      controls. This region is known for its implication in mood disorders, and its
      white matter compartment was previously found to display hypertrophic astrocytes
      in depressed suicides. Distributions of IBA1-immunoreactive (IBA-IR) microglial
      phenotypes were assessed using stereology and cell morphometry, and blood vessels
      were characterized as being intimately associated with either a high or a low
      density of IBA1-IR amoeboid-like cells. Total densities of IBA1-IR microglia did
      not differ between depressed suicides and controls. However, a finer analysis
      examining relative proportions of microglial phenotypes revealed that the ratio
      of primed over ramified ("resting") microglia was significantly increased in
      depressed suicides. Strikingly, the proportion of blood vessels surrounded by a
      high density of macrophages was more than twice higher in depressed suicides than
      in controls, and this difference was strongly significant. Consistent with these
      observations, gene expression of IBA1 and MCP-1, a chemokine involved in the
      recruitment of circulating monocytes, was significantly upregulated in depressed
      suicides. Furthermore, mRNA for CD45, a marker enriched in perivascular
      macrophages, was also significantly increased in samples from depressed suicides.
      An increase compared to controls was also observed in the proportion of blood
      vessels surrounded by a high density of CD45-IR cells, but this difference did
      not reach significance. These histological and molecular data suggest the
      recruitment of monocytes in dACC white matter of depressed suicides, although it
      cannot be excluded that other types of macrophages (including microglia) account
      for the observed accumulation of macrophages closely associated with blood
      vessels. Altogether, these findings suggest that the previously reported
      depression- and suicide-associated increases in circulating pro-inflammatory
      cytokines may be associated with low-grade cerebral neuroinflammation involving
      the recruitment of circulating monocytes. 

PMID- 24858660
TI  - Comparing characteristics of melanoma cases arising in health maintenance
      organizations with state and national registries.
AB  - Datasets from large health maintenance organizations (HMOs), particularly those
      with established cancer registries that report to the Surveillance, Epidemiology,
      and End Results program, are potentially excellent resources for studying
      melanoma epidemiology and outcomes. However, generalizability of the findings
      beyond HMO-based populations has not been well studied. We compared melanoma
      patient, tumor, and treatment characteristics at Kaiser Permanente Northern
      California and Henry Ford Healthcare Systems with those of corresponding
      regional, state, and national registry-reported melanoma databases. We identified
      all melanoma cases diagnosed at Kaiser Permanente Northern California (1996-2009)
      and Henry Ford Healthcare Systems (1996-2007) and ascertained patient (age, sex,
      race, and ethnicity), tumor (site, size, laterality, invasiveness, depth,
      ulceration, subtype, and stage), and treatment (surgery and radiation) variables
      from health system cancer registries. Registry data were obtained from
      Surveillance, Epidemiology, and End Results databases for the reporting period
      ending in November 2011. We found that melanoma cases arising in HMO settings
      generally have comparable patient, tumor, and treatment characteristics to
      regional, state, and national cases. An important difference included improved
      reporting of race information at HMO sites. Melanoma studies using data derived
      from select HMOs are potentially generalizable to local, state, and national
      populations, and may be better situated for studying racial-ethnic disparities. 

PMID- 24858661
TI  - Resistance surveillance in a BRAF mutant melanoma patient on long-term BRAF
      inhibitor treatment.
AB  - Treatment responses of BRAF mutant melanoma to BRAF inhibitors are often limited
      by the development of resistance. This case report describes the use of
      multiplatform molecular profiling in sequential surgical samples of a treatment
      resistant tumour site subjected to ongoing treatment with dabrafenib in a patient
      with metastatic cutaneous BRAF mutant melanoma. Next-generation sequencing showed
      the presence of the V600E, fibroblast growth factor receptor 2 (FGFR2),
      phosphatase and tensin homologue (PTEN) and p53 gene mutations. With a continuous
      presence of the BRAF V600E, FGFR2 and PTEN mutations and appearances of new
      mutations in the PTEN gene at R137H and T321fs and p53 R273C genes during ongoing
      treatment, this case report indicates intratumoural clonal evolution as a
      resistance mechanism. Two new mutations, the G542E exon 12 mutation variant of
      the FGFR2 gene and the R273C mutation variant of the p53 gene, are reported for
      the first time in BRAF mutant melanoma. 

PMID- 24858662
TI  - Biomarkers Affected by Impact Severity during Osteochondral Injury.
AB  - Osteochondral injury elevates the risk for developing posttraumatic
      osteoarthritis (PTOA). Therefore, our objective was to evaluate the relationship
      between impact severity during injury to cell viability and biomarkers possibly
      involved in PTOA. Osteochondral explants (6 mm, n = 72) were harvested from
      cadaveric femoral condyles (N = 6). Using a test machine, each explant (except
      for No Impact) was subjected to mechanical impact at a velocity of 100 mm/s to
      0.25, 0.5, 0.75, 1.0, or 1.25 mm maximum compression corresponding to Low, Low
      Moderate, Moderate, Moderate-High, or High impact groups. Cartilage cell
      viability, collagen content, and proteoglycan content were assessed at either day
      0 or after 12 days of culture. Culture media were assessed for prostaglandin E2
      (PGE2); nitric oxide; granulocyte macrophage colony-stimulating factor (GM-CSF);
      interferon gamma (IFNgamma); interleukin (IL)-2, -4, -6, -7, -8, -10, -15, -18;
      interferon gamma-induced protein 10 (IP-10); keratinocyte-derived chemoattractant
      (KC); monocyte chemoattractant protein-1 (MCP-1); tumor necrosis factor alpha
      (TNFalpha); and matrix metalloproteinase-2, -3, -8, -9, -13. There was increased
      impact energy absorbed for the High group compared with the Moderate-High group,
      Moderate group, and Low-Moderate group (p = 0.011, 0.048, 0.008, respectively).
      At day 0, there was decreased area cell viability for the High group compared
      with the Low-Moderate group (p = 0.035). At day 1, PGE2 was increased for the
      High group compared with the Moderate, Low-Moderate, Low, and No Impact groups (p
      <= 0.01). Cumulative PGE2 was increased for the Moderate-High and High groups
      compared with the Moderate, Low-Moderate, Low, and No Impact groups (p <= 0.036).
      At day 1, MCP-1 was increased for the Moderate-High and High groups compared with
      the Low and No Impact groups (p <= 0.032). Impact to osteochondral explants
      resulted in multiple levels of severity. PGE2 was sensitive to impact severity
      which may justify its use as a clinically measurable biomarker after joint injury
      for monitoring early PTOA. 

PMID- 24858664
TI  - Provision of and response to manuscript reviews.

PMID- 24858663
TI  - Functional characterization of mannose-binding lectin in zebrafish: implication
      for a lectin-dependent complement system in early embryos.
AB  - The lectin pathway involves recognition of pathogen-associated molecular patterns
      by mannose-binding lectin (MBL), and the subsequent activation of associated
      enzymes, termed MBL-associated serine proteases (MASPs). In this study, we
      demonstrate that the transcript of MBL gene is present in the early embryo of
      zebrafish, and MBL protein is also present in the embryo. In addition, we show
      that recombinant zebrafish MBL was able to bind the Gram-negative bacterium
      Escherichia coli and the Gram-positive bacterium Staphylococcus aureus, and rMBL
      was able to promote the phagocytosis of E. coli and S. aureus by macrophages,
      indicating that like mammalian MBL, zebrafish MBL performs a dual function in
      both pattern recognition and opsonization. Importantly, we show that
      microinjection of anti-MBL antibody into the early developing embryos resulted in
      a significantly increased mortality in the embryos challenged with Aeromonas
      hydrophila (pathogenic to zebrafish); and injection of rMBL into the embryos
      (resulting in increase in MBL in the embryo) markedly promoted their resistance
      to A. hydrophila; and this promoted bacterial resistance was significantly
      reduced by the co-injection of anti-MBL antibody with rMBL but not by the
      injection of anti-actin antibody with rMBL. These suggest that the lectin pathway
      may be already functional in the early embryos in zebrafish before their immune
      system is fully matured, protecting the developing embryos from microbial
      infection. This work provides a new angle to understand the immune role of the
      lectin pathway in early development of animals. 

PMID- 24858665
TI  - Water birth? Don't do it.

PMID- 24858666
TI  - Update From NANN on volunteering and new resources.

PMID- 24858667
TI  - Mosaic trisomy 9 hematopoietic chimera.
AB  - A 1.57-kg infant presented at a major medical center in the southeastern United
      States at 32 weeks of gestation with growth restriction and no major anomalies
      after an uncomplicated pregnancy. At 1 month of life, the infant was found to be
      chimeric for blood types O and A. Genetic testing revealed mosaic trisomy 9 as
      the cause for the 2 distinct blood types. Without phenotypic presentation of
      trisomy 9, the infant's genetic diagnosis was not detected until an issue arose.
      Genetic diagnosis and treatment and future considerations are discussed in this
      article. Full-text English articles from CINAHL and PubMed were analyzed for
      assistance in understanding the infant's condition. Book chapters, review
      articles, and meta-analyses were also reviewed. Implications of this case study
      indicate that phenotypically normal presenting infants may still have underlying
      issues that should be investigated genetically when they arise. This article
      cannot be generalized to the population because of its specific situation, but
      the underlying concept can be applied to any case. 

PMID- 24858668
TI  - The right tool at the right time: examining the evidence surrounding measurement
      of neonatal abstinence syndrome.

PMID- 24858669
TI  - A randomized-controlled trial pilot study examining the neurodevelopmental
      effects of a 5-week M Technique intervention on very preterm infants.
AB  - PURPOSE: To systematically test the cumulative effect of the M Technique on
      infant neurodevelopment in hospitalized very preterm infants. DESIGN: A pilot
      randomized controlled trial (RCT). SUBJECTS: Twenty very preterm infants (<30
      weeks gestation with average birth weights <1000 g) were randomly assigned to
      nontreatment or treatment groups. The study period began once the infants reached
      30 weeks postmenstrual age (PMA). METHODS: Each infant received standard neonatal
      intensive unit (NICU) care or standard NICU care plus a 7-minute M Technique
      session, 6 times per week for 5 weeks. Neurobehavioral development (using the
      NICU Network Neurobehavioral Scale [NNNS]) and growth velocity (difference in
      infant weight at the beginning and end of protocol) were compared between the 2
      groups. Physiologic parameters (heart rate, respiratory rate, and oxygen
      saturations) and infant behavioral states were measured 5 minutes before, during,
      and up to 10 minutes postintervention continuously on all infants in the
      treatment group at 3 different gestational time points (30, 32, and 34 weeks PMA)
      over the 5-week period. RESULTS: Mann-Whitney U analyses revealed no differences
      between the 2 groups on all 12 NNNS summary score domains but a difference in
      growth velocity between the 2 groups (P = 0.005). Repeated-measures analysis of
      variance revealed significant physiologic differences of mean heart rate,
      respiratory rate, and SaO2 (F = 41.116, P < 0.0005) and behavioral states (F =
      38.564, P < 0.0005) from baseline to 10 minutes after the M Technique
      intervention across all 3 time points. State scores decreased from baseline (M =
      6.11) to post intervention (M = 1.4) at all 3 time points. CONCLUSIONS: This
      pilot RCT demonstrates the utility of the M Technique in hospitalized very
      preterm infants starting at 30 weeks PMA with notable evidence of positive
      weight, physiological, and behavioral state adaptations. Additional research is
      needed with a larger, randomized design to determine short- and long-term effects
      specifically related to neurological outcomes.

PMID- 24858672
TI  - Neonatal intensive care practices: perceptions of parents, professionals, and
      managers.
AB  - PURPOSE: This article explores the differences and similarities in opinions of
      neonatal intensive care issues between parents, neonatal intensive care unit
      (NICU) healthcare professionals (nurses and physicians), and managers (neonatal
      unit managers and pediatric division managers). METHOD: An exploratory survey (n
      = 624) was conducted in Sweden during 2012-2013 on the basis of a validated
      questionnaire composed of 92 neonatal care-related Likert items. A total of 141
      parents, 443 professionals, and 40 managers completed the survey. The parents
      were recruited consecutively from 5 NICUs of the Vastra Gotaland region in Sweden
      and the professionals and managers from all 40 NICUs in Sweden. Data were
      analyzed with analysis of variances, and post hoc analyses were conducted through
      pairwise t tests with Bonferroni corrections. RESULT: Professionals and managers
      differed significantly on 1 item. Parents, however, found 54 items significantly
      less important than professionals did, but found only 4 to be significantly more
      important than professionals did. CONCLUSIONS: In line with previous research, we
      found that a gap exists between views of neonatal intensive care practices, with
      parents on one side and professionals and managers on the other. The nature of
      this gap, however, differs substantially from previous research, where parents
      found many items to be more important than professionals did. To develop and
      improve neonatal intensive care, this gap must be acknowledged and addressed,
      both in research and in practice. NICU managers need to develop strategies and
      routines that allow professionals to understand and adjust to the specific
      priorities of individual parents and families.

PMID- 24858670
TI  - Prevention and early recognition of necrotizing enterocolitis: a tale of 2 tools-
      eNEC and GutCheckNEC.
AB  - BACKGROUND AND SIGNIFICANCE: Risk for neonatal necrotizing enterocolitis (NEC) is
      complex, reflecting its multifactorial pathogenesis. PURPOSE: To improve risk
      awareness and facilitate communication among neonatal caregivers, especially
      nurses, 2 tools were developed. DESIGN: GutCheck was derived and validated as
      part of a formal research study over 3 phases, evidence synthesis, expert
      consensus building, and statistical modeling. The Wetzel/Krisman tool, eNEC, was
      developed and tested as part of a quality improvement initiative in a single
      clinical setting using evidence synthesis, review by internal expert clinicians,
      and implementation and evaluation of its use by direct line neonatal staff.
      Refinement of both tools is under way to evaluate their effect on clinical
      decision making, early identification of NEC and surgical NEC. METHODS AND MAIN
      OUTCOMES: Clinicians can take an active role to reduce NEC in their units by
      focusing on modifiable risk factors such as adoption of standardized feeding
      protocols, preferential feeding of human milk, and antibiotic and histamine
      blocker stewardship. RESULTS: Feeding during transfusion remains controversial,
      but judicious use of transfusions, adoption of transfusion guidelines, and
      withholding feeding during transfusion are feasible measures with potential
      benefit to prevent NEC and confer little risk.

PMID- 24858673
TI  - Direct, reagentless electrochemical detection of the BIR3 domain of X-linked
      inhibitor of apoptosis protein using a peptide-based conducting polymer sensor.
AB  - In this work, we report a reagentless electrochemical peptide (AVPFAQKG) sensor
      to directly detect the BIR3 domain of X-linked inhibitor of apoptosis protein
      (XIAP-BIR3). The bioreceptor was based on a conducting copolymer film
      electrosynthesized from juglone and a juglone-peptide conjugate (JP) newly
      designed. The peptide-protein interactions generated an important increase of
      steric hindrance at the interface and a current decrease (signal off) of the
      redox reaction from quinone embedded in the polymer backbone as evidenced by
      Square Wave Voltammetry. This allowed a specific and sensitive detection of XIAP
      BIR3 with a detection limit of 1 nM (13 ng mL(-1)). The peptide-protein complex
      could be then dissociated by adding the free precursor peptide (AVPFAQKG) into
      solution, causing a shift-back on the signal, i.e. an increase in the current
      intensity (signal-on). This "off-on" detection sequence was used in this work as
      a double verification of the specificity and this approach can be employed as a
      general way to increase the reliability of the results. In general, the approach
      described in this work may be inspired to develop other direct and reagentless
      electrochemical protein assays with high specificity and sensitivity.

PMID- 24858674
TI  - Counter electrode based on an ion-exchanger Donnan exclusion membrane for
      bioelectroanalysis.
AB  - Ion-exchanger based Donnan exclusion membranes (IEDEM) are studied here as
      separators for counter and pseudo-reference electrodes in bioelectroanalysis.
      Since the potential across the membrane remains indifferent for a wide range of
      current densities in contact with electrolyte solutions, IEDEM behave as ideally
      non-polarizable membranes. Consequently, such membranes may be suitable with
      counter or reference electrode, depending on the adopted cell configuration
      (three- or two-electrode system). Four configurations were characterized in order
      to establish the limitations of commercial anion-exchanging membranes, using
      chronopotentiometry as readout protocol. Three- and two-electrode configurations
      with and without membrane exhibited similar characteristics in terms of drift and
      reproducibility (observed drift and RSD were 0.0007 s(1/2) per scan number and
      1.71%, respectively). Several currents amplitudes were applied to evaluate the
      upper current limits for the membranes, which was found at about 10 mA [42.8 mA
      cm(-2)]. This value is significantly above those typically used in
      chronopotentiometric experiments, which involve hundreds of MUA. Three different
      analytes were measured in human whole blood using an IEDEM as a counter
      electrode. A divalent cation (calcium), a polyion (protamine), and an anion
      (chloride) were successfully determined in blood and compared to reference
      methods. Finally, the obtained results suggest that such membranes may be used in
      bioelectrochemical sensing approaches to replace expensive but less appropriate
      electrode materials for the measurement in matrices that contain lipids and
      proteins.

PMID- 24858675
TI  - Quantification of cardiac biomarkers using label-free and multiplexed gold
      nanorod bioprobes for myocardial infarction diagnosis.
AB  - Gold nanorod (GNR) is an attractive optical transducer for label-free biosensing
      owing to the localized surface plasmon resonance (LSPR) which is highly sensitive
      to the dielectric constant of the surrounding medium modulated by biological
      bindings. By adjusting the nanorod aspect ratio (length to width ratio), desired
      absorption wavelength can be continuously tuned from 600 to 1100 nm. Here we
      demonstrated a linear relationship between the aspect ratio and the LSPR peak
      wavelength. Taking advantage of this tunability feature, we developed a
      multiplexed GNR sensor by combining nanorods with distinct LSPR wavelengths.
      Specifically, GNRs of AR 2.1 and 4.2 exhibiting longitudinal plasmonic band of
      640 and 830 nm, respectively, were functionalized with specific antibody.
      Concentrations of multiple analytes were measured by correlating to the spectral
      shift at the distinct plasmon band maxima upon specific binding. The practical
      use of this mixed bioprobes for simultaneous quantification of cardiac biomarkers
      (myoglobin and cardiac troponin I) in the clinically significant sensing range
      was described. The LSPR red shift magnitude is linearly proportional to the
      increase in the target analyte concentration (R(2)=0.98). The calibration curve
      can clearly differentiate varying biomarker amounts with a high specificity. For
      multiplexed biosensing, the plasmon shift at the dedicated peak wavelength can be
      specifically correlated with spiked biomarker for simultaneous detection in the
      sample mixture. This technology can be further transformed onto miniaturized
      biochips based on the nanosized optical transducer to allow point-of-care blood
      testing for risk stratifications of cardiac patients in clinical settings.

PMID- 24858676
TI  - Growth of gold-manganese oxide nanostructures on a 3D origami device for glucose
      oxidase label based electrochemical immunosensor.
AB  - Flexible biosensors are of considerable current interest for the development of
      portable point-of-care medical products, minimally invasive implantable devices,
      and compact diagnostic platforms. Here, we reported an electrochemical paper
      based analytical device fabricated (EPADs) by sequentially growing gold
      nanoparticles (AuNPs) and manganese oxide (MnO2) nanowires networks on a
      freestanding three dimensional (3D) origami device. This fabricated through the
      growth of an AuNPs layer on the surfaces of cellulose fibers in the screen
      printed paper working electrode (PWE), and thus developed a gold paper working
      electrode (Au-PWE). Subsequently, MnO2 nanowires were successfully
      electrodeposited on Au-PWE to form a 3D network with large surface areas. Based
      on this novel EPADs and the principle of origami, we presented herein a simple
      immunosensing scheme using glucose oxidase (GOx) as an enzyme label, 3,3',5,5'
      tetramethylbenzidine (TMB) as a redox terminator, and glucose as an enzyme
      substrate. The electrochemical enzymatic redox cycling was applied to the
      detection of prostate protein antigen (PSA), a biomarker of prostatic cancer. The
      proposed method successfully fulfilled the highly sensitive detection of PSA with
      a linear range of 0.005 ng mL(-1)-100 ng mL(-1) with a detection limit of 0.0012
      ng mL(-1). This EPADs exhibited high sensitivity, specificity and excellent
      performance in real human serum assay, and could be applied in point-of-care
      testing of other tumor markers for remote regions and developing countries.

PMID- 24858677
TI  - Characterization of a phosphotriesterase-like lactonase from the
      hyperthermoacidophilic crenarchaeon Vulcanisaeta moutnovskia.
AB  - The phosphotriesterase-like lactonase (PLL) encoded by Vmut_2255 in the
      hyperthermoacidophilic crenarchaeon Vulcanisaeta moutnovskia (VmutPLL),
      represents the only hyperthermophilic PLL homologue identified so far in addition
      to the previously characterized thermophilic PLLs from Sulfolobus spp. The
      Vmut_2255 gene was cloned, heterologously expressed in Escherichia coli; the
      resultant protein purified and characterized as a 82kDa homodimer (36kDa
      subunits). The VmutPLL converted lactones and acyl-homoserine lactones (AHLs)
      with comparable activities. Towards organophosphates (OP) VmutPLL showed a
      promiscuous but significantly lower activity and only minor activity was observed
      with carboxylesters. The catalytic activity strictly depended on bivalent cations
      (Cd(2+)>Ni(2+)>Co(2+)>Mn(2+)>Zn(2+)). Furthermore, VmutPLL showed a pH optimum
      around 8.0, a temperature optimum of 80 degrees C, and thermostability with a
      half-life of 26min at 90 degrees C. In this work, the stereoselectivity of a PLL
      enzyme was investigated for the first time using enantiopure lactones. The
      VmutPLL showed a slight preference but not an exclusive specificity for the (R)
      enantiomers of capro- and valerolactone. The high thermal stability as well as
      the broad substrate spectrum towards lactones, AHLs and OPs underlines the high
      biotechnological potential of VmutPLL. 

PMID- 24858678
TI  - Three vitrification-based cryopreservation procedures cause different cryo
      injuries to potato shoot tips while all maintain genetic integrity in
      regenerants.
AB  - We previously reported successful cryopreservation of shoot tips of potato
      'Zihuabai' by three vitrification-based protocols. In the present study, cryo
      injury to shoot tips and genetic stability in regenerants recovered from
      cryopreserved shoot tips by the three vitrification-based protocols were further
      investigated. The results showed that sucrose preculture caused no obviously
      different injuries, while dehydration with plant vitrification solution 2 (PVS2)
      was the step causing major damage to cells of shoot tips, regardless of the
      cryogenic procedures. Compared with droplet-vitrification and encapsulation
      vitrification, vitrification caused the most severe injury to cells of the shoot
      tips, thus resulting in much longer time duration for shoot recovery and much
      lower shoot regrowth rate. Cells in apical dome and the youngest leaf primordia
      were able to survive and subsequently some of them regrew into shoots following
      all three vitrification-based cryopreservation procedures. Analyses using inter
      simple sequence repeat (ISSR) and amplified fragment length polymorphism (AFLP)
      markers in shoots regrown from all three vitrification-based protocols did not
      find any polymorphic bands. The results reported here suggest that vitrification
      based cryo-procedures can be considered promising methods for long-term
      preservation of potato genetic resources. 

PMID- 24858679
TI  - Carbon sink removal: Increased photosynthetic production of lactic acid by
      Synechocystis sp. PCC6803 in a glycogen storage mutant.
AB  - Deletion of pathways for carbon-storage in the cyanobacterium Synechocystis sp.
      PCC6803 has been suggested as a strategy to increase the size of the available
      pyruvate pool for the production of (heterologous) chemical commodities. Here we
      show that deletion of the pathway for glycogen synthesis leads to a twofold
      increased lactate production rate, under nitrogen-limited conditions, whereas
      impairment of polyhydroxybutyrate synthesis does not. 

PMID- 24858680
TI  - Methylation and subsequent glycosylation of 7,8-dihydroxyflavone.
AB  - An O-methyltransferase SpOMT2884, originating from Streptomyces peucetius ATCC
      27952, was cloned, expressed, and applied for the production of target metabolite
      from Escherichia coli. Biochemical characterization of the 25kDa recombinant
      protein by in vitro and in vivo experiments showed that SpOMT2884 was an S
      adenosyl-l-methionine-dependent O-methyltransferase. SpOMT2884 catalyzed O
      methylation of different classes of flavonoids such as flavones (7,8
      dihydroxyflavone (7,8-DHF), luteolin), flavonols (quercetin, rutin), flavanone
      (naringenin), and isoflavonoids (daidzein, formononetin). Biotransformation of
      7,8-DHF, a preferred substrate of SpOMT2884, in a grown-induced culture of E.
      coli BL21 (DE3) harboring the recombinant pET-28a-SpOMT2884 stoichiometrically
      converted 7,8-DHF into 7-hydroxy-8-methoxyflavone, which was confirmed by liquid
      chromatography, mass spectrometry and various nuclear magnetic resonance (NMR)
      spectroscopy analyses. In order to improve the biotransformation substrate, time
      and media parameters were optimized and the production was scaled up using a 3-L
      fermentor. The maximum yield of 7-hydroxy-8-methoxyflavone was 192MUM
      (52.57mg/L), representing almost 96% bioconversion within 12h, when 200MUM of 7,8
      DHF was supplemented in the culture. Further, the 7-hydroxy-8-methoxyflavone was
      purified in large scale and was used as a substrate separately for in vitro
      glycosylation to produce glucose, galactose and 2-deoxyglucose conjugated at 7th
      hydroxyl position of 7-hydroxy-8-methoxyflavone. Biological activity showed that
      7-hydroxy-8-methoxyflavone had long term cytoprotective and antioxidant effects
      compared to 7,8-DHF suggesting that methylation enhances the stability of
      substrate and glycosylation has proved to increase the water solubility. 

PMID- 24858681
TI  - Structural studies on a low oxygen affinity hemoglobin from mammalian species:
      sheep (Ovis aries).
AB  - Hemoglobin (Hb) is in equilibrium between low affinity Tense (T) and high
      affinity Relaxed (R) states associated with its unliganded and liganded forms,
      respectively. Mammalian species can be classified into two groups on the basis of
      whether they express 'high' and 'low' oxygen affinity Hbs. Although Hbs from
      former group have been studied extensively, a limited number of structural
      studies have been performed for the low oxygen affinity Hbs. Here, the crystal
      structure of low oxygen affinity sheep methemoglobin (metHb) has been determined
      to 2.7 A resolution. Even though sheep metHb adopts classical R state like
      quaternary structure, it shows localized quaternary and tertiary structural
      differences compared with other liganded Hb. The critical group of residues in
      the "joint region", shown as a major source of quaternary constraint on deoxyHb,
      formed unique interactions in the alpha1beta2/alpha2beta1 interfaces of sheep
      metHb structure. In addition, the constrained beta subunits heme environment and
      the contraction of N-termini and A-helices of beta subunits towards the molecular
      dyad are observed for sheep metHb structure. These observations provide the
      structural basis for a low oxygen affinity and blunt response to allosteric
      effector of sheep Hb.

PMID- 24858682
TI  - Inhibition of mTOR affects protein stability of OGT.
AB  - Autophagy regulates cellular homeostasis through degradation of aged or damaged
      subcellular organelles and components. Interestingly, autophagy-deficient beta
      cells, for example Atg7-mutant mice, exhibited hypoinsulinemia and hyperglycemia.
      Also, autophagy response is diminished in heart of diabetic mice. These results
      implied that autophagy and diabetes are closely connected and affect each other.
      Although protein O-GlcNAcylation is up-regulated in hyperglycemia and diabetes,
      and O-GlcNAcylated proteins play an important role in metabolism and nutrient
      sensing, little is known whether autophagy affects O-GlcNAc modification and vice
      versa. In this study, we suppressed the action of mTOR by treatment of mTOR
      catalytic inhibitors (PP242 and Torin1) to induce autophagic flux. Results showed
      a decrease in global O-GlcNAcylation, which is due to decreased OGT protein and
      increased OGA protein. Interestingly, knockdown of ATG genes or blocking of
      lysosomal degradation enhanced protein stability of OGT. In addition, when
      proteasomal inhibitor was treated together with mTOR inhibitor, protein level of
      OGT almost recovered to control level. These data suggest that mTOR inhibition is
      a more efficient way to reduce protein level of OGT rather than that of CHX
      treatment. We also showed that not only proteasomal degradation regulated OGT
      stability but autophagic degradation also affected OGT stability in part. We
      concluded that mTOR signaling regulates protein O-GlcNAc modification through
      adjustment of OGT stability. 

PMID- 24858683
TI  - Human monoclonal antibodies derived from a patient infected with 2009 pandemic
      influenza A virus broadly cross-neutralize group 1 influenza viruses.
AB  - Influenza viruses are a continuous threat to human public health because of their
      ability to evolve rapidly through genetic drift and reassortment. Three human
      monoclonal antibodies (HuMAbs) were generated in this study, 1H11, 2H5 and 5G2,
      and they cross-neutralize a diverse range of group 1 influenza A viruses,
      including seasonal H1N1, 2009 pandemic H1N1 (H1N1pdm) and avian H5N1 and H9N2.
      The three HuMAbs were prepared by fusing peripheral blood lymphocytes from an
      H1N1pdm-infected patient with a newly developed fusion partner cell line, SPYMEG.
      All the HuMAbs had little hemagglutination inhibition activity but had strong
      membrane-fusion inhibition activity against influenza viruses. A protease
      digestion assay showed the HuMAbs targeted commonly a short alpha-helix region in
      the stalk of the hemagglutinin. Furthermore, Ile45Phe and Glu47Gly double
      substitutions in the alpha-helix region made the HA unrecognizable by the HuMAbs.
      These two amino acid residues are highly conserved in the HAs of H1N1, H5N1 and
      H9N2 viruses. The HuMAbs reported here may be potential candidates for the
      development of therapeutic antibodies against group 1 influenza viruses. 

PMID- 24858685
TI  - Structural characterization and interaction of periostin and bone morphogenetic
      protein for regulation of collagen cross-linking.
AB  - Periostin appears to be a unique extracellular protein secreted by fibroblasts
      that is upregulated following injury to the heart or changes in the environment.
      Periostin has the ability to associate with other critical extracellular matrix
      (ECM) regulators such as TGF-beta, tenascin, and fibronectin, and is a critical
      regulator of fibrosis that functions by altering the deposition and attachment of
      collagen. Periostin is known to be highly expressed in carcinoma cells, but not
      in normal breast tissues. The protein has a structural similarity to insect
      fasciclin-1 (Fas 1) and can be induced by transforming growth factor-beta (TGF
      beta) and bone morphogenetic protein (BMP)-2. To investigate the molecular
      interaction of periostin and bone morphogenetic protein, we modeled these three
      dimensional structures and their binding sites. We demonstrated direct
      interaction between periostin and BMP1/2 in vitro using several biochemical and
      biophysical assays. We found that the structures of the first, second, and fourth
      Fas1 domains in periostin are similar to that of the fourth Fas 1 domain of
      TGFBIp. However, the structure of the third Fas 1 domain in periostin is
      different from those of the first, second, and fourth Fas1 domains, while it is
      similar to the NMR structure of Fasciclin-like protein from Rhodobacter
      sphaeroides. These results will useful in further functional analysis of the
      interaction of periostin and bone morphogenetic protein. 

PMID- 24858684
TI  - Global impact of Salmonella type III secretion effector SteA on host cells.
AB  - Salmonella enterica is a Gram-negative bacterium that causes gastroenteritis,
      bacteremia and typhoid fever in several animal species including humans. Its
      virulence is greatly dependent on two type III secretion systems, encoded in
      pathogenicity islands 1 and 2. These systems translocate proteins called
      effectors into eukaryotic host cell. Effectors interfere with host signal
      transduction pathways to allow the internalization of pathogens and their
      survival and proliferation inside vacuoles. SteA is one of the few Salmonella
      effectors that are substrates of both type III secretion systems. Here, we used
      gene arrays and bioinformatics analysis to study the genetic response of human
      epithelial cells to SteA. We found that constitutive synthesis of SteA in HeLa
      cells leads to induction of genes related to extracellular matrix organization
      and regulation of cell proliferation and serine/threonine kinase signaling
      pathways. SteA also causes repression of genes related to immune processes and
      regulation of purine nucleotide synthesis and pathway-restricted SMAD protein
      phosphorylation. In addition, a cell biology approach revealed that epithelial
      cells expressing steA show altered cell morphology, and decreased cytotoxicity,
      cell-cell adhesion and migration. 

PMID- 24858686
TI  - Pharmacological assessment of methamphetamine-induced behavioral hyperactivity
      mediated by dopaminergic transmission in planarian Dugesia japonica.
AB  - The freshwater planarian Dugesia japonica has a simple central nervous system
      (CNS) and can regenerate complete organs, even a functional brain. Recent studies
      demonstrated that there is a great variety of neuronal-related genes,
      specifically expressed in several domains of the planarian brain. We identified a
      planarian dat gene, named it D. japonica dopamine transporter (Djdat), and
      analyzed its expression and function. Both in situ hybridization and
      immunofluorescence revealed that localization of Djdat mRNA and protein was the
      same as that of D. japonica tyrosine hydroxylase (DjTH). Although, dopamine (DA)
      content in Djdat(RNAi) planarians was not altered, Djdat(RNAi) planarians showed
      increased spontaneous locomotion. The hyperactivity in the Djdat(RNAi) planarians
      was significantly suppressed by SCH23390 or sulpiride pretreatment, which are D1
      or D2 receptor antagonists, respectively. These results suggest that planarians
      have a Djdat ortholog and the ability to regulate dopaminergic neurotransmission
      and association with spontaneous locomotion. 

PMID- 24858687
TI  - The Fe-heme structure of met-indoleamine 2,3-dioxygenase-2 determined by X-ray
      absorption fine structure.
AB  - Multiple-scattering (MS) analysis of EXAFS data on met-indoleamine 2,3
      dioxygenase-2 (IDO2) and analysis of XANES have provided the first direct
      structural information about the axial donor ligands of the iron center for this
      recently discovered protein. At 10K, it exists in a low-spin bis(His) form with
      Fe-Np(av)=1.97A, the Fe-NIm bond lengths of 2.11A and 2.05A, which is in
      equilibrium with a high-spin form at room temperature. The bond distances in the
      low-spin form are consistent with other low-spin hemeproteins, as is the XANES
      spectrum, which is closer to that of the low-spin met-Lb than that of the high
      spin met-Mb. The potential physiological role of this spin equilibrium is
      discussed. 

PMID- 24858688
TI  - MicroRNA-497 inhibition of ovarian cancer cell migration and invasion through
      targeting of SMAD specific E3 ubiquitin protein ligase 1.
AB  - Ovarian cancer is the leading cause of death from gynecological malignancies
      worldwide. Understanding the molecular mechanism underlying ovarian cancer
      progression facilitates the development of promising strategy for ovarian cancer
      therapy. Previously, we observed frequent down-regulation of miR-497 expression
      in ovarian cancer tissues. In this study, we investigated the role of miR-497 in
      ovarian cancer metastasis. We found that endogenous miR-497 expression was down
      regulated in the more aggressive ovarian cancer cell lines compared with the less
      aggressive cells. Exogenous expression of miR-497 suppressed ovarian cancer cell
      migration and invasion, whereas reduction of endogenous miR-497 expression
      induced tumor cell migration and invasion. Mechanistic investigations confirmed
      pro-metastatic factor SMURF1 as a direct target of miR-497 through which miR-497
      ablated tumor cell migration and invasion. Further studies revealed that lower
      levels of miR-497 expression were associated with shorter overall survival as
      well as increased SMURF1 expression in ovarian cancer patients. Our results
      indicate that down-regulation of miR-497 in ovarian cancer may facilitate tumor
      metastasis. Restoration of miR-497 expression may be a promising strategy for
      ovarian cancer therapy. 

PMID- 24858689
TI  - Smooth muscle progenitor cells from peripheral blood promote the
      neovascularization of endothelial colony-forming cells.
AB  - Proangiogenic cell therapy using autologous progenitors is a promising strategy
      for treating ischemic disease. Considering that neovascularization is a
      harmonized cellular process that involves both endothelial cells and vascular
      smooth muscle cells, peripheral blood-originating endothelial colony-forming
      cells (ECFCs) and smooth muscle progenitor cells (SMPCs), which are similar to
      mature endothelial cells and vascular smooth muscle cells, could be attractive
      cellular candidates to achieve therapeutic neovascularization. We successfully
      induced populations of two different vascular progenitor cells (ECFCs and SMPCs)
      from adult peripheral blood. Both progenitor cell types expressed endothelial
      specific or smooth muscle-specific genes and markers, respectively. In a protein
      array focused on angiogenic cytokines, SMPCs demonstrated significantly higher
      expression of bFGF, EGF, TIMP2, ENA78, and TIMP1 compared to ECFCs. Conditioned
      medium from SMPCs and co-culture with SMPCs revealed that SMPCs promoted cell
      proliferation, migration, and the in vitro angiogenesis of ECFCs. Finally, co
      transplantation of ECFCs and SMPCs induced robust in vivo neovascularization, as
      well as improved blood perfusion and tissue repair, in a mouse ischemic hindlimb
      model. Taken together, we have provided the first evidence of a cell therapy
      strategy for therapeutic neovascularization using two different types of
      autologous progenitors (ECFCs and SMPCs) derived from adult peripheral blood. 

PMID- 24858690
TI  - Folate in demethylation: the crystal structure of the rat dimethylglycine
      dehydrogenase complexed with tetrahydrofolate.
AB  - Dimethylglycine dehydrogenase (DMGDH) is a mammalian mitochondrial enzyme which
      plays an important role in the utilization of methyl groups derived from choline.
      DMGDH is a flavin containing enzyme which catalyzes the oxidative demethylation
      of dimethylglycine in vitro with the formation of sarcosine (N-methylglycine),
      hydrogen peroxide and formaldehyde. DMGDH binds tetrahydrofolate (THF) in vivo,
      which serves as an acceptor of formaldehyde and in the cell the product of the
      reaction is 5,10-methylenetetrahydrofolate instead of formaldehyde. To gain
      insight into the mechanism of the reaction we solved the crystal structures of
      the recombinant mature and precursor forms of rat DMGDH and DMGDH-THF complexes.
      Both forms of DMGDH reveal similar kinetic parameters and have the same tertiary
      structure fold with two domains formed by N- and C-terminal halves of the
      protein. The active center is located in the N-terminal domain while the THF
      binding site is located in the C-terminal domain about 40A from the isoalloxazine
      ring of FAD. The folate binding site is connected with the enzyme active center
      via an intramolecular channel. This suggests the possible transfer of the
      intermediate imine of dimethylglycine from the active center to the bound THF
      where they could react producing a 5,10-methylenetetrahydrofolate. Based on the
      homology of the rat and human DMGDH the structural basis for the mechanism of
      inactivation of the human DMGDH by naturally occurring His109Arg mutation is
      proposed. 

PMID- 24858692
TI  - Structural basis of the phosphorylation dependent complex formation of
      neurodegenerative disease protein Ataxin-1 and RBM17.
AB  - Spinocerebellar Ataxia Type1 (SCA1) is a dominantly inherited neurodegenerative
      disease and belongs to polyglutamine expansion disorders. The polyglutamine
      expansion in Ataxin-1 (ATXN1) is responsible for SCA1 pathology. ATXN1 forms at
      least two distinct complexes with Capicua (CIC) or RNA-binding motif protein 17
      (RBM17). The wild-type ATXN1 dominantly forms a complex with CIC and the
      polyglutamine expanded form of ATXN1 favors to form a complex with RBM17. The
      phosphorylation of Ser776 in ATXN1 is critical for SCA1 pathology and serves as a
      binding platform for RBM17. However, the molecular basis of the phospho-specific
      binging of ATXN1 to RBM17 is not delineated. Here, we present the modeled
      structure of RBM17 bound to the phosphorylated ATXN1 peptide. The structure
      reveals the phosphorylation specific interaction between ATXN1 and RBM17 through
      a salt-bridge network. Furthermore, the modeled structure and the interactions
      between RBM17 and ATXN1 were validated through mutagenesis study followed by
      Surface Plasmon Resonance binding experiments. This work delineates the molecular
      basis of the interaction between RBM17 and the phosphorylated form of ATXN1,
      which is critical for SCA1 pathology. Furthermore, the structure of RBM17 and
      pATXN1 peptide might be utilized to target RBM17-ATXN1 interaction to modulate
      SCA1 pathogenesis. 

PMID- 24858691
TI  - JUNB promotes the survival of Flavopiridol treated human breast cancer cells.
AB  - Chemotherapy resistance is a major obstacle to achieving durable progression-free
      survival in breast cancer patients. Identifying resistance mechanisms is crucial
      to the development of effective breast cancer therapies. Immediate early genes
      (IEGs) function in the initial cellular reprogramming response to alterations in
      the extracellular environment and IEGs have been implicated in cancer cell
      development and progression. The purpose of this study was to investigate the
      influence of kinase inhibitors on IEG expression in breast cancer cells. The
      results demonstrated that Flavopiridol (FP), a CDK9 inhibitor, effectively
      reduced gene expression. FP treatment, however, consistently produced a delayed
      induction of JUNB gene expression in multiple breast cancer cell lines. Similar
      results were obtained with Sorafenib, a multi-kinase inhibitor and U0126, a MEK1
      inhibitor. Functional studies revealed that JUNB plays a pro-survival role in
      kinase inhibitor treated breast cancer cells. These results demonstrate a unique
      induction of JUNB in response to kinase inhibitor therapies that may be among the
      earliest events in the progression to treatment resistance. 

PMID- 24858693
TI  - Identification of a novel multiple kinase inhibitor with potent antiviral
      activity against influenza virus by reducing viral polymerase activity.
AB  - Neuraminidase inhibitors are the only currently available influenza treatment,
      although resistant viruses to these drugs have already been reported. Thus, new
      antiviral drugs with novel mechanisms of action are urgently required. In this
      study, we identified a novel antiviral compound, WV970, through cell-based
      screening of a 50,000 compound library and subsequent lead optimization. This
      compound exhibited potent antiviral activity with nanomolar IC50 values against
      both influenza A and B viruses but not non-influenza RNA viruses. Time-of
      addition and indirect immunofluorescence assays indicated that WV970 acted at an
      early stage of the influenza life cycle, but likely after nuclear entry of viral
      ribonucleoprotein (vRNP). Further analyses of viral RNA expression and viral
      polymerase activity indicated that WV970 inhibited vRNP-mediated viral genome
      replication and transcription. Finally, structure-based virtual screening and
      comprehensive human kinome screening were used to demonstrate that WV970 acts as
      a multiple kinase inhibitor, many of which are associated with influenza virus
      replication. Collectively, these results strongly suggest that WV970 is a
      promising anti-influenza drug candidate and that several kinases associated with
      viral replication are promising drug targets. 

PMID- 24858694
TI  - Charophyte electrogenesis as a biomarker for assessing the risk from low-dose
      ionizing radiation to a single plant cell.
AB  - The impact of low-dose ionizing radiation on the electrical signalling pattern
      and membrane properties of the characea Nitellopsis obtusa was examined using
      conventional glass-microelectrode and voltage-clamp techniques. The giant cell
      was exposed to a ubiquitous radionuclide of high biological importance - tritium 
      for low-dose irradiation. Tritium was applied as tritiated water with an
      activity concentration of 15 kBq L(-1) (an external dose rate that is
      approximately 0.05 MUGy h(-1) above the background radiation level); experiments
      indicated that this was the lowest effective concentration. Investigating the
      dynamics of electrical excitation of the plasma membrane (action potential)
      showed that exposing Characeae to tritium for half an hour prolonged the
      repolarization phase of the action potential by approximately 35%: the
      repolarization rate decreased from 39.2 +/- 3.1 mV s(-1) to 25.5 +/- 1,8 mV s(-1)
      due to tritium. Voltage-clamp measurements showed that the tritium exposure
      decreased the Cl(-) efflux and Ca(2+) influx involved in generating an action
      potential by approximately 27% (Delta = 12.4 +/- 1.1 MUA cm(-2)) and 64% (Delta =
      -5.3 +/- 0.4 MUA cm(-2)), respectively. The measured alterations in the action
      potential dynamics and in the chloride and calcium ion transport due to the
      exogenous low-dose tritium exposure provide the basis for predicting possible
      further impairments of plasma membrane regulatory functions, which subsequently
      disturb essential physiological processes of the plant cell. 

PMID- 24858695
TI  - A chiral high-performance liquid chromatography-tandem mass spectrometry method
      for the stereospecific determination of morinidazole in human plasma.
AB  - Morinidazole is a novel 5-nitroimidazole derivative used for the treatment of
      amoebiasis, trichomoniasis, and anaerobic bacterial infections. Morinidazole
      possesses a chiral carbon and is clinically administered as a racemate. In the
      present study, an enantioselective and sensitive liquid chromatography-tandem
      mass spectrometry method of determining morinidazole enantiomers in human plasma
      was developed and validated to characterize the stereoselective pharmacokinetics.
      Plasma samples were processed by liquid-liquid extraction using tert-butyl methyl
      ether. Chiral separation was optimized within 8.5min on a cellulose column using
      an isocratic mobile phase of methanol/water (80:20, v/v). Detection was using
      mass spectrometry in multiple reaction monitoring mode, using the transitions of
      m/z 271->144 for morinidazole enantiomers, and m/z 275->148 for d4-morinidazole
      (internal standard). The calibration curves were linear over 5.00-6000ng/mL for
      each enantiomer. The lower limit of quantification for each enantiomer was
      established at 5.00ng/mL. Intra- and inter-day precisions were less than 6.4% for
      each enantiomer in terms of relative standard deviation, and accuracies were
      between -2.5% and 6.4% in terms of relative error for each enantiomer. No chiral
      inversion was observed during sample storage, preparation procedure and analysis.
      Major glucuronide and sulfate conjugates were not observed to interfere with the
      determination of morinidazole enantiomers. The method was applied to study the
      stereoselective pharmacokinetics of morinidazole in humans. Moderate
      stereoselectivity was observed in healthy subjects and patients with severe renal
      impairment. 

PMID- 24858696
TI  - Dexamethasone modifies mitomycin C-triggered interleukin-8 secretion in isolated
      human Tenon's capsule fibroblasts.
AB  - Intraoperative mitomycin C (MMC) is widely used to prevent pterygium recurrence
      and glaucoma filtering bleb failure, but it has been shown to induce corneal
      inflammation and cell death. Postoperative dexamethasone (DEX) is advocated to
      reduce MMC-related inflammation and cell death in corneal fibroblasts.
      Nevertheless, its long-term regulation mechanism in Tenon's capsule remains to be
      explored. The purpose of this study was to investigate how DEX modifies MMC's
      effects in human Tenon's capsule fibroblasts (HTFs). HTFs isolated from the
      pterygium surgical patients (n = 6) were treated with MMC at 0, 0.1, 0.2, and 0.4
      mg/ml for 5 min and incubated in DEX at 10 MUM for 0, 1, 2, and 3 days.
      Recombinant interleukin-8 (IL-8) was used to verify the effect of MMC-related IL
      8 secretion. Cell proliferation of all the treated cells was analyzed by WST-1
      assay. The amount of IL-8 secretion in HTFs was determined by enzyme-linked
      immunosorbent assay. Immunoblotting assay was used to analyze the expression of
      peroxisome-proliferator-activated receptor gamma (PPARgamma) and B-cell lymphoma
      extra large (Bcl-xL). Our results revealed that MMC significantly reduced the HTF
      cell proliferation rate. Additionally, MMC significantly upregulated IL-8
      secretion in HTFs concentration-dependently. At 3 days post treatment (dpt), 5
      min exposures to 0.1, 0.2, and 0.4 mg/ml MMC resulted in 1.4-fold (p = 0.012),
      1.6-fold (p = 0.012), and 2.5-fold (p = 0.001) increases of IL-8 secretion. In
      contrast, DEX reversed the MMC-retarded cell proliferation rate (p = 0.036) and
      repressed MMC-related IL-8 secretion by 33.5% at 3 dpt (p = 0.003). Addition of
      recombinant IL-8 noticeably suppressed HTF cell proliferation in a concentration
      dependent manner. DEX stimulated upregulation of both PPARgamma and Bcl-xL at 1
      dpt in normal HTFs and at 2 dpt in MMC-treated HTFs. PPARgamma silencing reduced
      expression of PPARgamma and Bcl-xL, but enhanced IL-8 secretion (p < 0.001). On
      the other hand, Bcl-xL silencing enhanced IL-8 secretion (p < 0.001), but did not
      affect PPARgamma expression. These revealed that IL-8 secretion in HTFs is
      modulated by PPARgamma-dependent Bcl-xL signaling. We conclude that DEX reversed
      the MMC-inhibited HTF cell proliferation via diminishing the MMC-induced IL-8
      secretion, which resulted from a late-phase upregulation of the PPARgamma and Bcl
      xL. These long-term effects suggest a beneficial postoperative DEX treatment
      following intraoperative MMC application. 

PMID- 24858697
TI  - Selective suppression of autocatalytic caspase-3 driven by two-step
      transcriptional amplified human telomerase reverse transcriptase promoter on
      ovarian carcinoma growth in vitro and in mice.
AB  - The objective of our study was to construct recombinant adenovirus (rAd)
      AdHTVP2G5-rev-casp3, which expresses autocatalytic caspase-3 driven by human
      telomerase reverse transcriptase promoter (hTERTp) with a two-step transcription
      amplification (TSTA) system and investigate its antitumor effects on ovarian
      cancer in vitro and in vivo. Fluorescent detection was used to detect EGFP
      expression in various cells. Cell viabilities were determined using the Cell
      Counting Kit-8 and flow cytometry. RT-PCR and immunoblotting assays were used to
      detect cellular apoptotic activities. Tumor growth and survival of tumor-bearing
      mice were studied. The hTERTp-TSTA system showed the strongest activity in hTERT
      positive cancer cells when compared with hTERTp and cytomeglovirus promoter
      (CMVp). In contrast, it showed no activity in hTERT-negative HUVECs. AdHTVP2G5
      rev-casp3 markedly suppressed the survival of AO cells in a dose-dependent
      modality with a viability rate of 17.8 +/- 3.5% at an MOI of 70, which was
      significantly lower than that by AdHT-rev-casp3 and Ad-rev-casp3 (rAds which
      express rev-caspase-3 driven by hTERTp and CMVp, respectively). In contrast,
      AdHTVP2G5-rev-casp3 induced little HUVEC death with a viability rate of 92.7 +/-
      5.2% at the same MOI. Additionally, AdHTVP2G5-rev-casp3 (MOI=70) caused
      significant apoptosis in AO cells with an apoptotic rate of 42%. The tumor growth
      suppression rate of AdHTVP2G5-rev-casp3 was 81.52%, significantly higher than
      that of AdHT-rev-casp3 (54.94%) or Ad-rev-casp3 (21.35%). AdHTVP2G5-rev-casp3
      significantly improved the survival of tumor-bearing mice with little liver
      damage, with a mean survival of 258 +/- 28 days. These results showed that
      AdHTVP2G5-rev-casp3 caused effective apoptosis with significant tumor
      selectivity, strongly suppressed tumor growth and improved mouse survival with
      little liver toxicity. It can be a potent therapeutic agent for tumor targeted
      treatment of ovarian cancer.

PMID- 24858698
TI  - Radix astragali inhibits the down-regulation of connexin 26 in the stria
      vascularis of the guinea pig cochlea after acoustic trauma.
AB  - Connexin 26 (cx26) plays an important role in the intercellular signaling and is
      related to K(+) metabolism in stria vascularis (SV). Reactive oxygen species
      (ROS) are negative regulators of cx26, reducing intercellular coupling in
      cochlea. ROS plays an important role in acoustic trauma. Radix astragali is a
      natural antioxidant that decreases impulse noise-induced hearing loss through its
      ability to inhibit ROS. The purpose of this study was to investigate if radix
      astragali has the potential to reduce the change of cx26 in SV from impulse
      noise. Guinea pigs in the experimental group were administered radix astragali
      intraperitoneally. Auditory thresholds were assessed by sound-evoked auditory
      brainstem response (ABR) at click and tone bursts of 8, 16 and 32 kHz, 24 h
      before and 72 h after exposure to impulse noise. 4-Hydroxynonenal, cx26 and KCNQ1
      were determined immunohistochemically in SV. SV was analyzed by transmission
      electron microscopy. Radix astragali significantly reduced the ABR deficits and
      the SV damage, and decreased the shifts of the expression of cx26 and KCNQ1 in
      the SV. These results suggest that the beneficial effect of radix astragali on
      impulse noise-induced hearing loss may be also due to its ability to reduce the
      change of cx26 in SV.

PMID- 24858700
TI  - Novel Acanthamoeba 18S rRNA gene sequence type from an environmental isolate.
AB  - The free-living amoebae, Acanthamoeba, can act as opportunistic parasites on a
      wide range of vertebrates and are becoming a serious threat to human health due
      to the resistance of their cysts to harsh environmental conditions,
      disinfectants, some water treatment practices, and their ubiquitous distribution.
      Subgenus classification based on morphology is being replaced by a classification
      based on the sequences of the 18S rRNA gene with a total of 18 different
      genotypes (T1-T18). A new environmental strain of Acanthamoeba isolated from a
      waste water treatment plant is presented in this study as a candidate for the
      description of the novel genotype T19 after phylogenetic analysis. 

PMID- 24858701
TI  - Cellular effects of bacterial N-3-Oxo-dodecanoyl-L-Homoserine lactone on the
      sponge Suberites domuncula (Olivi, 1792): insights into an intimate inter-kingdom
      dialogue.
AB  - Sponges and bacteria have lived together in complex consortia for 700 million
      years. As filter feeders, sponges prey on bacteria. Nevertheless, some bacteria
      are associated with sponges in symbiotic relationships. To enable this
      association, sponges and bacteria are likely to have developed molecular
      communication systems. These may include molecules such as N-acyl-L-homoserine
      lactones, produced by Gram-negative bacteria also within sponges. In this study,
      we examined the role of N-3-oxododecanoyl-L-homoserine lactone (3-oxo-C12-HSL) on
      the expression of immune and apoptotic genes of the host sponge Suberites
      domuncula. This molecule seemed to inhibit the sponge innate immune system
      through a decrease of the expression of genes coding for proteins sensing the
      bacterial membrane: a Toll-Like Receptor and a Toll-like Receptor Associated
      Factor 6 and for an anti-bacterial perforin-like molecule. The expression of the
      pro-apoptotic caspase-like 3/7 gene decreased as well, whereas the level of mRNA
      of anti-apoptotic genes Bcl-2 Homolog Proteins did not change. Then, we
      demonstrated the differential expression of proteins in presence of this 3-oxo
      C12-HSL using 3D sponge cell cultures. Proteins involved in the first steps of
      the endocytosis process were highlighted using the 2D electrophoresis protein
      separation and the MALDI-TOF/TOF protein characterization: alpha and beta
      subunits of the lysosomal ATPase, a cognin, cofilins-related proteins and
      cytoskeleton proteins actin, alpha tubulin and alpha actinin. The genetic
      expression of some of these proteins was subsequently followed. We propose that
      the 3-oxo-C12-HSL may participate in the tolerance of the sponge apoptotic and
      immune systems towards the presence of bacteria. Besides, the sponge may sense
      the 3-oxo-C12-HSL as a molecular evidence of the bacterial presence and/or
      density in order to regulate the populations of symbiotic bacteria in the sponge.
      This study is the first report of a bacterial secreted molecule acting on sponge
      cells and regulating the symbiotic relationship. 

PMID- 24858702
TI  - Filaggrin gene mutation c.3321delA is associated with various clinical features
      of atopic dermatitis in the Chinese Han population.
AB  - BACKGROUND: We confirmed that the filaggrin gene mutation c.3321delA is
      associated with atopic dermatitis in our previous genome wide association study
      of the Chinese Han population. c.3321delA is the most common filaggrin gene
      mutation in Chinese atopic dermatitis patients but is not present in European
      populations. OBJECTIVE: To investigate the genetic model for the c.3321delA
      mutation and to determine the correlation between c.3321delA and atopic
      dermatitis clinical phenotypes in the Chinese Han population. METHOD: The
      filaggrin gene mutation c.3321delA was sequenced in 1,080 atopic dermatitis
      patients and 908 controls from the Chinese population. The chi2 test,
      ANOVA,nonparametric tests and logistic regression were used to investigate the
      relationship between the c.3321delA genotype and atopic dermatitis clinical
      phenotypes in the Chinese Han population. RESULTS: Analyses of the genetic model
      revealed that the additive model best described the c.3321delA mutation (P =
      3.09E-11, OR = 3.43, 95%CI = 2.38-4.96). Stratified analyses showed that the
      c.3321delA allele frequency distribution is significantly associated with
      concomitant skin xerosis (P = 1.68E-03, OR = 2.13,95%CI = 1.32-3.46), palmar
      hyperlinearity (P = 3.64E-17, OR = 4.0,95%CI = 2.86-5.70), white dermatographism
      (P = 4.25E-03, OR = 1.82,95%CI = 1.22-2.71), food intolerance (P = 1.51E-03, OR =
      1.76,95%CI = 1.23-2.50) and disease severity ( P = 9.67E-05). CONCLUSION: Our
      study indicates that the filaggrin gene mutation c.3321delA is associated with
      clinical phenotypes of atopic dermatitis in the Chinese Han population, which
      might help us gain a better understanding on the pathogenesis of atopic
      dermatitis.

PMID- 24858703
TI  - Drosophila p53 controls Notch expression and balances apoptosis and
      proliferation.
AB  - A balance between cell proliferation and apoptosis is important for normal
      development and tissue homeostasis. Under stress conditions, the conserved tumor
      suppressor and transcription factor Dp53 induces apoptosis to contribute to the
      maintenance of homeostasis. However, in some cases Dp53-induced apoptosis results
      in the proliferation of surrounding non-apoptotic cells. To gain insight into the
      Dp53 function in the control of apoptosis and proliferation, we studied the
      interaction between the Drosophila Dp53 and Notch genes. We present evidence that
      simultaneous reduction of Dp53 and Notch function synergistically increases the
      wing phenotype of Notch heterozygous mutant flies. Further, we found that a Notch
      cis-regulatory element is responsive to loss and gain of Dp53 function and that
      over-expression of Dp53 up-regulates Notch mRNA and protein expression. These
      findings suggest not only that Dp53 and Notch act together to control wing
      development but also indicate that Dp53 transcriptionally regulates Notch
      expression. Moreover, using Notch  gain and loss of function mutations we
      examined the relevance of Dp53 and Notch interactions in the process of Dp53
      apoptosis induced proliferation. Results show that proliferation induced by Dp53
      over-expression is dependent on Notch, thus identifying Notch as a new player in
      Dp53-induced proliferation. Interestingly, we found that Dp53-induced Notch
      activation and proliferation occurs even under conditions where apoptosis was
      inhibited. Our findings highlight the conservation between flies and vertebrates
      of the Dp53 and Notch cross-talk and suggest that Dp53 has a dual role regulating
      cell death and proliferation gene networks to control the homeostatic balance
      between apoptosis and proliferation. 

PMID- 24858704
TI  - DDT and HCH, two discontinued organochlorine insecticides in the Great Lakes
      region: isomer trends and sources.
AB  - The uses of the insecticides 1,1'-(2,2,2-trichloroethylidene)bis[4-chlorobenzene]
      (p,p'-DDT) and gamma-hexachlorocyclohexane (gamma-HCH) have been discontinued for
      several years, but they are still consistently detected in air samples collected
      on the shores of the Great Lakes. Although the agricultural uses of DDT have been
      restricted in the United States since 1972, DDT continued to be used to
      manufacture the miticide, dicofol, up until 2011. The use of the technical HCH
      mixture in North America was restricted in the 1970s, when it was replaced by one
      of its purified conformers, gamma-HCH, also known as lindane. In this study, we
      have focused on isomer-specific data to gain insights on the temporal trends and
      possible sources of these compounds. In particular, we calculated ratios of the
      concentrations of p,p'-DDE+p,p'-DDD versus the sum of the concentrations of the
      three p,p' isomers. These ratios are about the same at all five of our sampling
      sites and are about the same as observed globally. We also calculated the ratio
      of the concentrations of o,p'-DDT versus the sum of concentrations of o,p'
      DDT+p,p'-DDT. This ratio has increased significantly at all five sites over the
      last 15-20 years. We suggest that dicofol, which contained about 11% o,p'-DDT,
      may now be a significant, additional source of DDT to the Great Lakes. The
      average ratio of the concentration of gamma-HCH (lindane) versus the sum of the
      concentrations of gamma-HCH+alpha-HCH did not vary significantly with time, but
      it did show an urban signature, suggesting that cities may be more important
      sources of these compounds than previously suspected.

PMID- 24858699
TI  - Autoimmune and autoinflammatory mechanisms in uveitis.
AB  - The eye, as currently viewed, is neither immunologically ignorant nor sequestered
      from the systemic environment. The eye utilises distinct immunoregulatory
      mechanisms to preserve tissue and cellular function in the face of immune
      mediated insult; clinically, inflammation following such an insult is termed
      uveitis. The intra-ocular inflammation in uveitis may be clinically obvious as a
      result of infection (e.g. toxoplasma, herpes), but in the main infection, if any,
      remains covert. We now recognise that healthy tissues including the retina have
      regulatory mechanisms imparted by control of myeloid cells through receptors
      (e.g. CD200R) and soluble inhibitory factors (e.g. alpha-MSH), regulation of the
      blood retinal barrier, and active immune surveillance. Once homoeostasis has been
      disrupted and inflammation ensues, the mechanisms to regulate inflammation,
      including T cell apoptosis, generation of Treg cells, and myeloid cell
      suppression in situ, are less successful. Why inflammation becomes persistent
      remains unknown, but extrapolating from animal models, possibilities include
      differential trafficking of T cells from the retina, residency of CD8(+) T cells,
      and alterations of myeloid cell phenotype and function. Translating lessons
      learned from animal models to humans has been helped by system biology approaches
      and informatics, which suggest that diseased animals and people share similar
      changes in T cell phenotypes and monocyte function to date. Together the data
      infer a possible cryptic infectious drive in uveitis that unlocks and drives
      persistent autoimmune responses, or promotes further innate immune responses.
      Thus there may be many mechanisms in common with those observed in
      autoinflammatory disorders. 

PMID- 24858705
TI  - Features of patients with gastrointestinal bleeding after implantation of
      ventricular assist devices.
AB  - BACKGROUND & AIMS: Ventricular assist devices (VADs) are used to treat patients
      with end-stage heart disease. However, patients with VADs frequently develop
      gastrointestinal (GI) bleeding. We investigated the incidence, etiology, and
      outcome of GI bleeding in patients with VADs. METHODS: In a retrospective study,
      we analyzed data from 391 consecutive patients (mean age, 53.9 +/- 14.2 years;
      81% male) who underwent VAD implantation for end-stage heart disease from January
      2000 through May 2012 at the Cleveland Clinic. Multivariable logistic regression
      analysis was used to identify factors independently associated with GI bleeding
      in patients with VADs. RESULTS: Sixty-two patients (15.9%) had GI bleeding. The
      risk of GI bleeding increased by 10% for every 5-year increase in age (P = .006).
      GI bleeding was also associated with lower body mass index (P = .046), current
      smoking (P = .007), and lower baseline levels of hemoglobin (P < .001). Bleeding
      was primarily overt (79%), and most patients presented with hematochezia (43.5%).
      Causes of bleeding were primarily vascular malformations (26.5%) and ulcers
      (26.5%). Patients who received VADs as their only therapy, rather than as a
      bridge-to-transplantation, were more likely to have GI bleeding (P = .008).
      Colonoscopy detected GI bleeding with the highest diagnostic yield; most bleeding
      was associated with colonic lesions (51.4%). Overall mortality was 39.4%, and 2
      deaths were directly related to GI bleeding. CONCLUSIONS: On the basis of a large
      case series analysis, GI bleeding is common after implantation of VADs (15.9% of
      patients have at least 1 episode of bleeding). Episodes were mostly overt and
      predominantly from the lower GI tract; colonoscopy is the best method of
      detection.

PMID- 24858706
TI  - Current and future applications of natural language processing in the field of
      digestive diseases.
AB  - Natural language processing (NLP) is a technology that uses computer-based
      linguistics and artificial intelligence to identify and extract information from
      free-text data sources such as progress notes, procedure and pathology reports,
      and laboratory and radiologic test results. With the creation of large databases
      and the trajectory of health care reform, NLP holds the promise of enhancing the
      availability, quality, and utility of clinical information with the goal of
      improving documentation, quality, and efficiency of health care in the United
      States. To date, NLP has shown promise in automatically determining appropriate
      colonoscopy intervals and identifying cases of inflammatory bowel disease from
      electronic health records. The objectives of this review are to provide
      background on NLP and its associated terminology, to describe how NLP has been
      used thus far in the field of digestive diseases, and to identify its potential
      future uses. 

PMID- 24858710
TI  - Subregional DXA-derived vertebral bone mineral measures are stronger predictors
      of failure load in specimens with lower areal bone mineral density, compared to
      those with higher areal bone mineral density.
AB  - Measurement of areal bone mineral density (aBMD) in intravertebral subregions may
      increase the diagnostic sensitivity of dual-energy X-ray absorptiometry (DXA)
      derived parameters for vertebral fragility. This study investigated whether DXA
      derived bone parameters in vertebral subregions were better predictors of
      vertebral bone strength in specimens with low aBMD, compared to those with higher
      aBMD. Twenty-five lumbar vertebrae (15 embalmed and 10 fresh-frozen) were scanned
      with posteroanterior- (PA) and lateral-projection DXA, and then mechanically
      tested in compression to ultimate failure. Whole-vertebral aBMD and bone mineral
      content (BMC) were measured from the PA- and lateral-projection scans and within
      6 intravertebral subregions. Multivariate regression was used to predict ultimate
      failure load by BMC, adjusted for vertebral size and specimen fixation status
      across the whole specimen set, and when subgrouped into specimens with low aBMD
      and high aBMD. Adjusted BMC explained a substantial proportion of variance in
      ultimate vertebral load, when measured over the whole vertebral area in lateral
      projection (adjusted R (2) 0.84) and across the six subregions (ROIs 2-7)
      (adjusted R (2) range 0.58-0.78). The association between adjusted BMC, either
      measured subregionally or across the whole vertebral area, and vertebral failure
      load, was increased for the subgroup of specimens with identified 'low aBMD',
      compared to those with 'high aBMD', particularly in the anterior subregion where
      the adjusted R (2) differed by 0.44. The relative contribution of BMC measured in
      vertebral subregions to ultimate failure load is greater among specimens with
      lower aBMD, compared to those with higher aBMD, particularly in the anterior
      subregion of the vertebral body. 

PMID- 24858708
TI  - Advanced drug and gene delivery systems based on functional biodegradable
      polycarbonates and copolymers.
AB  - Biodegradable polymeric nanocarriers are one of the most promising systems for
      targeted and controlled drug and gene delivery. They have shown several unique
      advantages such as excellent biocompatibility, prolonged circulation time,
      passive tumor targeting via the enhanced permeability and retention (EPR) effect,
      and degradation in vivo into nontoxic products after completing their tasks. The
      current biodegradable drug and gene delivery systems exhibit, however, typically
      low in vivo therapeutic efficacy, due to issues of low loading capacity,
      inadequate in vivo stability, premature cargo release, poor uptake by target
      cells, and slow release of therapeutics inside tumor cells. To overcome these
      problems, a variety of advanced drug and gene delivery systems has recently been
      designed and developed based on functional biodegradable polycarbonates and
      copolymers. Notably, polycarbonates and copolymers with diverse functionalities
      such as hydroxyl, carboxyl, amine, alkene, alkyne, halogen, azido, acryloyl,
      vinyl sulfone, pyridyldisulfide, and saccharide, could be readily obtained by
      controlled ring-opening polymerization. In this paper, we give an overview on
      design concepts and recent developments of functional polycarbonate-based
      nanocarriers including stimuli-sensitive, photo-crosslinkable, or active
      targeting polymeric micelles, polymersomes and polyplexes for enhanced drug and
      gene delivery in vitro and in vivo. These multifunctional biodegradable
      nanosystems might be eventually developed for safe and efficient cancer
      chemotherapy and gene therapy. 

PMID- 24858711
TI  - Clinical setting influences patterns of interaction between osteoporosis patient
      and physician.
AB  - The importance of healthy behavior for bone health, as well as low adherence to
      anti-osteoporosis medication are well-described problems. Both, lifestyle habits
      and compliance with drug-therapy are influenced by the relationship between
      patients and physicians. We analyzed 152 consecutive doctor-patient interactions
      conducted in public and private practices specialized in the management of
      osteoporosis. We recorded the duration of the consultation and the relative
      length of: (a) Personal and medical history collection, (b) Physical examination,
      (c) Explanation of the diagnosis and treatment modalities, and (d) Administrative
      tasks. The overall length and the respective duration of the four phases of the
      consultation significantly differ in private versus public practices. In the
      private practice, doctors spend more time with the patient and dedicate a higher
      proportion of their time to history collection and explanation of
      diagnosis/treatment for osteoporosis. While we do not integrate data on
      medication adherence, we believe that since more time is dedicated to health
      education, patients consulting in the private sector have a greater probability
      to adopt a healthy lifestyle and better/ longer take anti-osteoporosis
      medications. Further investigations are needed to assess if the differences in
      patient and doctor behaviors in the public-private settings have a significant
      impact on therapeutic adherence and subsequently fracture reduction in patients
      receiving anti-osteoporosis treatment. 

PMID- 24858709
TI  - Inflammation, telomere length, and grip strength: a 10-year longitudinal study.
AB  - Telomere attrition has been associated with age-related diseases, although
      causality is unclear and controversial; low-grade systemic inflammation
      (inflammaging) has also been implicated in age-related pathogenesis. Unpicking
      the relationship between aging, telomere length (TL), and inflammaging is hence
      essential to the understanding of aging and management of age-related diseases.
      This longitudinal study explored whether telomere attrition is a cause or
      consequence of aging and whether inflammaging explains some of the associations
      between TL and one marker of aging, grip strength. We studied 253 Hertfordshire
      Ageing Study participants at baseline and 10-year follow-up (mean age at baseline
      67.1 years). Participants completed a health questionnaire and had blood samples
      collected for immune-endocrine and telomere analysis at both time points.
      Physical aging was characterized at follow-up using grip strength. Faster
      telomere attrition was associated with lower grip strength at follow-up (beta =
      0.98, p = 0.035). This association was completely attenuated when adjusted for
      inflammaging burden (p = 0.86) over the same period. Similarly, greater
      inflammaging burden was associated with lower grip strength at follow-up (e.g.,
      interleukin [IL]-1beta: beta = -2.18, p = 0.001). However, these associations
      were maintained when adjusted for telomere attrition (IL-1beta, p = 0.006). We
      present evidence that inflammaging may be driving telomere attrition and in part
      explains the associations that have previously been reported between TL and grip
      strength. Thus, biomarkers of physical aging, such as inflammaging, may require
      greater exploration. Further work is now indicated.

PMID- 24858712
TI  - MiR-20a is upregulated in anaplastic thyroid cancer and targets LIMK1.
AB  - BACKGROUND: There have been conflicting reports regarding the function of miR-20a
      in a variety of cancer types and we previously found it to be dysregulated in
      sporadic versus familial papillary thyroid cancer. In this study, we studied the
      expression of miR-20a in normal, benign and malignant thyroid samples, and its
      effect on thyroid cancer cells in vitro and in vivo. METHODOLOGY/PRINCIPAL
      FINDINGS: The expression of miR-20a in normal, benign and malignant thyroid
      tissue was determined by quantitative RT-PCR. Thyroid cancer cells were
      transfected with miR-20a and the effect on cellular proliferation, tumor spheroid
      formation, and invasion was evaluated. Target genes of miR-20 were determined by
      genome-wide mRNA expression analysis with miR-20a overexpression in thyroid
      cancer cells and target prediction database. Target genes were validated by
      quantitative PCR and immunoblotting, and luciferase assays. MiR-20a expression
      was significantly higher in anaplastic thyroid cancer than in differentiated
      thyroid cancer, and benign and normal thyroid tissues. MiR-20a significantly
      inhibited thyroid cancer cell proliferation in vitro (p<0.01) and in vivo
      (p<0.01), tumor spheroid formation (p<0.05) and invasion (p<0.05) in multiple
      thyroid cancer cell lines. We found that LIMK1 was a target of miR-20a in thyroid
      cancer cell lines and direct knockdown of LIMK1 recapitulated the effect of miR
      20a in thyroid cancer cells. CONCLUSIONS/SIGNIFICANCE: To our knowledge, this is
      the first study to demonstrate that miR-20a plays a role as a tumor suppressor in
      thyroid cancer cells and targets LIMK1. Our findings suggest the upregulated
      expression of miR-20a in anaplastic thyroid cancer counteracts thyroid cancer
      progression and may have therapeutic potential.

PMID- 24858714
TI  - Diversin is overexpressed in breast cancer and accelerates cell proliferation and
      invasion.
AB  - Diversin was recently reported to play roles in Wnt and JNK pathways. However,
      the expression pattern and biological roles of diversin in human breast cancer
      have not been reported. In the present study, we found that diversin was
      overexpressed in breast cancer specimens by immunohistochemistry and western
      blot. Significant association was observed between diversin overexpression and
      TNM stage (p = 0.0036), nodal metastasis (p = 0.0033), negative estrogen receptor
      expression (p = 0.0012) and triple-negative status (p = 0.0017). Furthermore,
      colony formation assay and matrigel invasion assay showed that knockdown of
      diversin expression in MDA-MB-231 cell line with high endogenous expression
      decreased cell proliferation and cell invasion. Transfection of diversin plasmid
      in MCF-7 cell line increased cell proliferation and invasion. Further analysis
      showed that diversin depletion downregulated JNK phosphorylation while its
      overexpression upregulated JNK phosphorylation. In conclusion, our study
      demonstrated that diversin was overexpressed in human breast cancers. Diversin
      could contribute to breast cancer cell proliferation and invasion. 

PMID- 24858715
TI  - High frequency of genital human papillomavirus infections and related cervical
      dysplasia in adolescent girls in Belgium.
AB  - Human papillomavirus (HPV) infections are causally related to cervical cancer and
      a range of other diseases, both in adults and in minors. Information on the
      frequency of genital HPV infections in adolescents is sparse. The aim of this
      study was to gain insight into the genotype-specific distribution of HPV
      genotypes in patients younger than 18 years of age. This observational
      retrospective study included 4807 samples of patients presenting for
      opportunistic screening in Belgium between June 2006 and January 2012. For
      statistical analysis, only the first visits of patients were withheld, reducing
      the sample to 4180. Samples were collected in liquid-based cytology medium and
      analyzed using a series of genotype-specific real-time PCR reactions. Cytology
      was read with previous knowledge of HPV infection and scored using the Bethesda
      classification. The mean age was 16.9 years. Most youngsters had no complaints
      (88.4%), were using hormonal contraception (79.5%), and clinical examination did
      not show any abnormalities (96.0%). The overall HPV frequency was 15.7%, with the
      most frequently found types being HPV16 (16.7%), HPV51 (14.6%), HPV66 (10.4%),
      HPV31 (9.9%), and HPV39 (9.1%). More than one-third (39.0%) of the infected girls
      harbored an infection with at least two HPV genotypes. Cytological abnormalities
      were found in 8.2% of samples. L-SIL (4.2%) was most frequently observed,
      followed by ASC-US (3.6%), HSIL (0.3%), and ASC-H (0.1%). The severity of lesions
      worsened with increasing age. Our findings indicate that an aberrant HPV genotype
      profile can be found in adolescent girls; moreover, this group shows a high rate
      of cervical abnormalities. 

PMID- 24858716
TI  - Light exposure at night, sleep duration, melatonin, and breast cancer: a dose
      response analysis of observational studies.
AB  - Evidence from observational studies on light at night (LAN) exposure, sleep
      duration, endogenous melatonin levels, and risk for breast cancer in women is
      conflicting. This led us to conduct a dose-response analysis of published
      observational data. Pertinent studies were identified by searching Medline, Web
      of Science, and EMBASE through April 2013. The dose-response relationship between
      sleep duration, urinary 6-sulphatoxymelatonin levels, and breast cancer was
      assessed using the restricted cubic spline model and by multivariate random
      effects metaregression. A separate meta-analysis was also carried out to
      calculate the relative risks (RRs) with 95% confidence intervals (CIs) for breast
      cancer for the comparable categories or highest levels of exposure versus the
      lowest levels. Twelve case-control and four cohort studies were included in the
      analysis. High artificial LAN exposure is associated with an increased risk for
      breast cancer (RR=1.17, 95% CI: 1.11-1.23), but not ambient LAN exposure
      (RR=0.91, 95% CI: 0.78-1.07). The summary RR for breast cancer is 1.00 (95% CI:
      0.995-1.01) for an increment of 1 h of sleep per night. No significant dose
      response relationship between sleep duration and breast cancer was found either
      for the linearity test (Ptrend=0.725) or for the nonlinearity (Ptrend=0.091)
      test. An increasein of 15 ng/mg creatinine in urinary 6-sulphatoxymelatonin is
      associated with a 14% reduced risk for breast cancer (RR=0.86, 95% CI: 0.78
      0.95), with a linear dose-response trend (Ptrend=0.003). There was no evidence of
      substantial heterogeneity or publication bias in the analysis. Our study adds to
      the evidence of LAN breast cancer theory. Further research in this area is
      warranted. 

PMID- 24858717
TI  - Relationship between tea consumption and pancreatic cancer risk: a meta-analysis
      based on prospective cohort studies and case-control studies.
AB  - The aim of this study was to evaluate the relationship between regular tea
      consumption and the risk of pancreatic cancer by a meta-analysis. Two
      investigators independently performed a computer retrieve on the electronic
      databases of Embase, PubMed, and Ovidsp for prospective cohort studies and case
      control studies on regular tea consumption and the risk of pancreatic cancer
      incidence. The keywords using for search were ('Pancreas' OR 'pancreatic') AND
      ('neoplasms' OR 'carcinoma' OR 'cancer') AND 'tea'. Risk ratios (RRs) and 95%
      confidence interval (CI) were used to determine the effect of tea consumption on
      pancreatic cancer. A total of 14 studies were included (8078 pancreatic cancer
      patients, with a total of 859 783 patients) in the present meta-analysis. The
      pooled results of effect size indicated that tea consumption has no significant
      relationship with risk of pancreatic cancer (RR=0.99, 95% CI: 0.89-1.11,
      P=0.922). However, the subgroup analysis of different countries showed a
      statistical decrease in pancreatic cancer risk by high consumption of tea in a
      Chinese population (RR=0.76, 95% CI: 0.59-0.98, P=0.036). Similar results were
      found in the elderly (>60 years old) (RR=0.76, 95% CI: 0.60-0.96, P=0.023). In
      conclusion, the present meta-analysis of 14 studies suggests that the correlation
      between tea consumption and the risk of pancreatic cancer in the general
      population is not significant, but an increase in tea consumption can reduce the
      risk of pancreatic cancer disease in Chinese populations and in individuals older
      than 60 years of age. It is necessary to formulate more rigorous designs of
      regional studies to further confirm the relationship between tea consumption and
      pancreatic cancer. 

PMID- 24858718
TI  - Current advances on ABC drug transporters in fish.
AB  - Most members of the large ATP-binding cassette (ABC) gene family are transporters
      involved in substrate translocation across biological membranes. In eukaryotes,
      ABC proteins functioning as drug transporters are located in the plasma membrane
      and mediate the cellular efflux of a wide range of organic chemicals, with some
      transporters also transporting certain metals. As the enhanced expression of ABC
      drug transporters can confer multidrug resistance (MDR) to cancers and
      multixenobiotic resistance (MXR) to organisms from polluted habitats, these ABC
      family members are also referred to as MDR or MXR proteins. In mammals, ABC drug
      transporters show predominant expression in tissues involved in excretion or
      constituting internal or external body boundaries, where they facilitate the
      excretion of chemicals and their metabolites, and limit chemical uptake and
      penetration into "sanctuary" sites of the body. Available knowledge about ABC
      proteins is still limited in teleost fish, a large vertebrate group of high
      ecological and economic importance. Using transport activity measurements and
      immunochemical approaches, early studies demonstrated similarities in the tissue
      distribution of ABC drug transporters between teleosts and mammals, suggesting
      conserved roles of the transporters in the biochemical defence against toxicants.
      Recently, the availability of teleost genome assemblies has stimulated studies of
      the ABC family in this taxon. This review summarises the current knowledge
      regarding the genetics, functional properties, physiological function, and
      ecotoxicological relevance of teleostean ABC transporters. The available
      literature is reviewed with emphasis on recent studies addressing the tissue
      distribution, substrate spectrum, regulation, physiological function and
      phylogenetic origin of teleostean ABC transporters. 

PMID- 24858719
TI  - Osthole improves an accelerated focal segmental glomerulosclerosis model in the
      early stage by activating the Nrf2 antioxidant pathway and subsequently
      inhibiting NF-kappaB-mediated COX-2 expression and apoptosis.
AB  - Inflammatory reactions and oxidative stress are implicated in the pathogenesis of
      focal segmental glomerulosclerosis (FSGS), a common chronic kidney disease with
      relatively poor prognosis and unsatisfactory treatment regimens. Previously, we
      showed that osthole, a coumarin compound isolated from the seeds of Cnidium
      monnieri, can inhibit reactive oxygen species generation, NF-kappaB activation,
      and cyclooxygenase-2 expression in lipopolysaccharide-activated macrophages. In
      this study, we further evaluated its renoprotective effect in a mouse model of
      accelerated FSGS (acFSGS), featuring early development of proteinuria, followed
      by impaired renal function, glomerular epithelial cell hyperplasia lesions (a
      sensitive sign that precedes the development of glomerular sclerosis),
      periglomerular inflammation, and glomerular hyalinosis/sclerosis. The results
      show that osthole significantly prevented the development of the acFSGS model in
      the treated group of mice. The mechanisms involved in the renoprotective effects
      of osthole on the acFSGS model were mainly a result of an activated Nrf2-mediated
      antioxidant pathway in the early stage (proteinuria and ischemic collapse of the
      glomeruli) of acFSGS, followed by a decrease in: (1) NF-kappaB activation and COX
      2 expression as well as PGE2 production, (2) podocyte injury, and (3) apoptosis.
      Our data support that targeting the Nrf2 antioxidant pathway may justify osthole
      being established as a candidate renoprotective compound for FSGS. 

PMID- 24858720
TI  - Roles of sedentary aging and lifelong physical activity in exchange of
      glutathione across exercising human skeletal muscle.
AB  - Reactive oxygen species (ROS) are important signaling molecules with regulatory
      functions, and in young and adult organisms, the formation of ROS is increased
      during skeletal muscle contractions. However, ROS can be deleterious to cells
      when not sufficiently counterbalanced by the antioxidant system. Aging is
      associated with accumulation of oxidative damage to lipids, DNA, and proteins.
      Given the pro-oxidant effect of skeletal muscle contractions, this effect of age
      could be a result of excessive ROS formation. We evaluated the effect of acute
      exercise on changes in blood redox state across the leg of young (23 +/- 1 years)
      and older (66 +/- 2 years) sedentary humans by measuring the whole blood
      concentration of the reduced (GSH) and oxidized (GSSG) forms of the antioxidant
      glutathione. To assess the role of physical activity, lifelong physically active
      older subjects (62 +/- 2 years) were included. Exercise increased the venous
      concentration of GSSG in an intensity-dependent manner in young sedentary
      subjects, suggesting an exercise-induced increase in ROS formation. In contrast,
      venous GSSG levels remained unaltered during exercise in the older sedentary and
      active groups despite a higher skeletal muscle expression of the superoxide
      generating enzyme NADPH oxidase. Arterial concentration of GSH and expression of
      antioxidant enzymes in skeletal muscle of older active subjects were increased.
      The potential impairment in exercise-induced ROS formation may be an important
      mechanism underlying skeletal muscle and vascular dysfunction with sedentary
      aging. Lifelong physical activity upregulates antioxidant systems, which may be
      one of the mechanisms underlying the lack of exercise-induced increase in GSSG.

PMID- 24858721
TI  - Impact of venous thromboembolism on survival in patients with advanced cancer: an
      unmet clinical need.

PMID- 24858722
TI  - Update on prognostic factors in acromegaly: Is a risk score possible?
AB  - Certain clinical conditions and markers have recently been demonstrated to modify
      the natural history of acromegaly in affected patients. Thus, some clinical,
      histological, radiological and molecular factors are associated with more
      aggressive pituitary tumors that have higher biochemical activity, higher tumor
      volumes and decreased tumoral and biochemical responses to current therapies.
      However, these factors do not seem to have an equal influence on the prognosis of
      patients with acromegaly. We present a review of the factors that influence the
      clinical course of patients with acromegaly and propose a risk value for each
      factor that will allow prognostic scoring for affected patients by considering a
      combination of these factors. 

PMID- 24858723
TI  - [Gastrointestinal stromal tumors: diagnostics and therapy].
AB  - Gastrointestinal stromal tumors (GIST) are the most frequent mesenchymal tumors
      of the gastrointestinal tract. The standard therapy is complete surgical
      resection with safety margins of 1-2 cm. Intraoperative rupture of the tumor
      capsule must be avoided because this carries a very high risk of tumor spread. A
      lymph node dissection is not routinely indicated as lymph node metastases very
      rarely occur with GIST. Smaller GISTs can normally be removed laparoscopically
      according to the rules of tumor surgery. Depending on the size of the tumor, the
      mitosis index and the localization of the primary tumor, the risk of recurrence
      after potentially curative resection is considerable in many cases. Patients with
      intermediate and high risks according to Miettinen's classification should
      receive adjuvant treatment with the tyrosine kinase inhibitor imatinib.
      Exceptions are those patients whose tumors exhibit the mutation D842V in exon18
      of the PDGFRA gene. According to current European Society for Medical Oncology
      (ESMO) guidelines this therapy should be continued for 3 years. This leads to a
      significant improvement in progression-free survival compared to a 1-year
      therapy, and more important to an improvement in overall survival.

PMID- 24858724
TI  - Stevioside plays an anti-inflammatory role by regulating the NF-kappaB and MAPK
      pathways in S. aureus-infected mouse mammary glands.
AB  - Mastitis is an inflammatory disease caused by microbial infection. Staphylococcus
      aureus is one of the primary bacteria responsible for mastitis. Stevioside is
      isolated from Stevia rebaudiana and is known to have therapeutic functions. This
      study was designed to evaluate the effects of stevioside in a mouse model of S.
      aureus-induced mastitis. In this study, the mouse mammary gland was infected with
      S. aureus to induce the mastitis model. The stevioside was administered
      intraperitoneally after the S. aureus infection was established. Hematoxylin
      eosin (HE) staining, ELISA, Western blot, and q-PCR methods were used. The
      results show that stevioside significantly reduced the inflammatory cell
      infiltration and the levels of TNF-alpha, IL-1beta, and IL-6 and the respective
      expression of their messenger RNAs (mRNAs). Further studies revealed that
      stevioside downregulated the TLR2, NF-kappaB, and (mitogen-activated protein
      kinase) MAPK signaling pathways in the S. aureus-infected mouse mammary gland.
      Our results demonstrate that stevioside reduced the expression of TNF-alpha, IL
      1beta, and IL-6 by inhibiting the phosphorylation of proteins in the NF-kappaB
      and MAPK signaling pathways dose-dependently, but that their mRNA expression was
      not obviously changed. 

PMID- 24858725
TI  - Glyceraldehyde-3-phosphate dehydrogenase is an inappropriate housekeeping gene
      for normalising gene expression in sepsis.
AB  - Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) has long been used as a default
      reference gene in quantitative mRNA profiling experiments. However, its
      expression reportedly varies in response to a range of pathophysiological
      variables (inflammation, oxidative stress, hyperinsulinaemia, hypoxia) which
      feature prominently in sepsis. We therefore assessed the applicability of using
      GAPDH as a reference gene for expression studies in sepsis compared to other
      housekeeping genes (succinate dehydrogenase complex subunit A (SDHA),
      hypoxanthine phosphoribosyltransferase (HPRT)-1). Severe sepsis resulted in a
      42.4-fold increase in median GAPDH expression (P<0.001), whereas median HPRT
      expression was raised more modestly (2.9-fold; P<0.001), and there was no
      significant difference in SDHA expression between sepsis and control patients.
      HPRT was identified by NormFinder to be the most stably expressed single gene. In
      order to assess the impact of this variability on data interpretation,
      interleukin (IL)-10 expression was normalised separately to GAPDH and to the
      geometric mean of HPRT and SDHA. In the former case, there was no significant
      difference in IL-10 expression between controls and septic patients, whilst in
      the latter, a significant 8.5-fold increase in median IL-10 expression was noted
      (P<0.001). GAPDH is thus an unreliable housekeeping gene for normalising gene
      expression in sepsis which should be replaced by alternative, validated reference
      genes.

PMID- 24858726
TI  - The differential roles of mTOR, ERK, and JNK pathways in invariant natural killer
      T-cell function and survival.
AB  - Invariant natural killer T (iNKT) cell is a critical element for both innate and
      adaptive immunity. The quick responses of mature iNKT cells to TCR stimulation
      require activation of several different signaling pathways. However, the roles of
      these signaling pathways in mature iNKT cell biology remain incompletely
      understood. To address this issue, single signaling pathway was blocked with
      inhibitor in iNKT cells, and the roles of these signaling pathways were
      estimated. Results showed that mammalian target of rapamycin (mTOR) plays an
      essential role for cytokine production and survival in iNKT cells. In contrast,
      ERK and JNK are more important for iNKT cell effector function, but not survival.
      Our findings delineate the distinct roles of different signaling pathways in
      mature iNKT cells and therefore shed new light for modulating iNKT cell function
      in disease conditions. 

PMID- 24858728
TI  - Sleep/wake problems in Parkinson's disease: pathophysiology and clinicopathologic
      correlations.
AB  - In his initial description of shaking palsy, James Parkinson first noted that
      sleep became disturbed with advancing paralysis agitans. More recent studies have
      confirmed that the majority of patients with Parkinson's disease (PD) suffer from
      some sleep disturbances. This can manifest as difficulty in falling or staying
      asleep, fractionated sleep, specific parasomnias, and daytime sleepiness. In this
      article, we will explore the pathophysiology of these varied sleep disorders. In
      most cases, however, the definitive etiology is debated, and phenotypes are often
      felt to be multifactorial. Some of these may be associated with dopaminergic
      dysfunction, some presumed to arise from varied non-dopaminergic PD pathology,
      and some from PD treatments. 

PMID- 24858727
TI  - Polypharmacy in the treatment of subjects with intellectual disability.
AB  - People with intellectual disabilities often suffer from mental disorders or
      display challenging behavior. For both impairments, treatment with more than one
      psychopharmacological drug is common, although little is known about efficacy and
      side effects of polypharmacological treatment. The paper reviews studies on
      treatment of people with intellectual disability (ID) with more than one
      psychoactive drug. Many studies rely on poor evidence and are supplemented with
      data from our own research. Risks and benefits of different combinations
      containing neuroleptics are listed. Ethical considerations for the use of
      different drugs combined are discussed. The use of combinations of neuroleptics
      on people with ID should be carried out with great care, since side effects may
      be amplified in people with ID, depending on the combination. 

PMID- 24858729
TI  - Use of lipolanthionine peptide, a toll-like receptor 2 inhibitor, enhances
      transdermal delivery efficiency.
AB  - The transdermal delivery system (TDS) is able to obtain a systemic therapeutic
      effect by administration through the skin, which has low side effects and is able
      to maintain a sustained blood concentration. However, due to the barrier
      presented by the stratum corneum, numerous drugs have poor percutaneous
      permeability. Therefore, the improvement of skin permeability is key to TDS. The
      main method of promoting transdermal absorption is through the usage of
      penetration enhancers. Dimethyl sulfoxide (DMSO) is a commonly used penetration
      enhancer, which has anti-inflammatory analgesic effects and is able to penetrate
      the skin. Retinoic acid (RA) and lipolanthionine peptide (LP) may also benefit
      the permeation efficiency of TDS. Therefore, the present study examined the
      function of DMSO, RA and LP as penetration enhancers in TDS. Firstly, the optimum
      concentration of DMSO was confirmed by detecting the expression of the LacZ gene
      in vitro. Secondly, different combinations of LP, RA and DMSO were applied to
      mouse skin to analyze the penetration enhancer combination with the greatest
      efficacy. All the animals were divided into five groups: The RA + LP + DMSO +
      pORF-LacZ group, the RA + DMSO + pORF-LacZ group, the LP + DMSO + pORF-LacZ
      group, the DMSO + pORF-LacZ group and the control group. Skin was soaked in
      combinations of LP, RA and DMSO for seven days and then the pORF-LacZ plasmids
      were daubed onto the skin once daily three days. On the 11th day, all the animals
      were sacrificed by cervical dislocation and the skin and blood samples were
      collected. The blood samples were used to detect the expression of the LacZ gene
      by quantitative polymerase chain reaction and the skin samples were used to
      detect the expression of claudin-4 and zonula occluden-1 (ZO-1) proteins by
      immunohistochemistry and western blot analysis. The results demonstrated that the
      combination of LP, RA and DMSO exhibited the greatest transdermal delivery
      efficiency, which verified that RA and LP were able to increase the penetration
      effects. Following treatment with LP, the symptoms of dermal edema were relieved
      and the capillaries contracted, which suggested that LP was a safe and effective
      penetration enhancer able to reduce the side-effects caused by DMSO. The present
      study provides a guideline for the synthesis of novel penetration enhancers. 

PMID- 24858730
TI  - Environmental enrichment restores CA1 hippocampal LTP and reduces severity of
      seizures in epileptic mice.
AB  - We have analyzed the effects of environmental enrichment (EE) in a seizure-prone
      mouse model in which the genetic disruption of the presynaptic protein Bassoon
      leads to structural and functional alterations in the hippocampus and causes
      early spontaneous seizures mimicking human neurodevelopmental disorders. One
      month EE starting at P21 reduced seizure severity, preserved long-term
      potentiation (LTP) and paired-pulse synaptic responses in the hippocampal CA1
      neuronal population and prevented the reduction of spine density and dendrite
      branching of pyramidal neurons. These data demonstrate that EE exerts its
      therapeutic effect by normalizing multiple aspects of hippocampal function and
      provide experimental support for its use in the optimization of existent
      treatments. 

PMID- 24858732
TI  - Influence of hydrothermal treatment on physicochemical properties and drug
      release of anti-inflammatory drugs of intercalated layered double hydroxide
      nanoparticles.
AB  - The synthesis method of layered double hydroxides (LDHs) determines
      nanoparticles' performance in biomedical applications. In this study,
      hydrothermal treatment as an important synthesis technique has been examined for
      its influence on the physicochemical properties and the drug release rate from
      drug-containing LDHs. We synthesised MgAl-LDHs intercalated with non-steroidal
      anti-inflammatory drugs (i.e., naproxen, diclofenac and ibuprofen) using a co
      precipitation method with or without hydrothermal treatment (150  degrees C, 4
      h). After being hydrothermally treated, LDH-drug crystallites increased in
      particle size and crystallinity, but did not change in the interlayer anion
      orientation, gallery height and chemical composition. The drug release patterns
      of all studied LDH-drug hybrids were biphasic and sustained. LDHs loaded with
      diclofenac had a quicker drug release rate compared with those with naproxen and
      ibuprofen, and the drug release from the hydrothermally-treated LDH-drug was
      slower than the freshly precipitated LDH-drug. These results suggest that the
      drug release of LDH-drugs is influenced by the crystallite size of LDHs, which
      can be controlled by hydrothermal treatment, as well as by the drug molecular
      physicochemical properties. 

PMID- 24858731
TI  - Escherichia coli O157:H7 super-shedder and non-shedder feedlot steers harbour
      distinct fecal bacterial communities.
AB  - Escherichia coli O157:H7 is a major foodborne human pathogen causing disease
      worldwide. Cattle are a major reservoir for this pathogen and those that shed E.
      coli O157:H7 at >104 CFU/g feces have been termed "super-shedders". A rich
      microbial community inhabits the mammalian intestinal tract, but it is not known
      if the structure of this community differs between super-shedder cattle and their
      non-shedding pen mates. We hypothesized that the super-shedder state is a result
      of an intestinal dysbiosis of the microbial community and that a "normal"
      microbiota prevents E. coli O157:H7 from reaching super-shedding levels. To
      address this question, we applied 454 pyrosequencing of bacterial 16S rRNA genes
      to characterize fecal bacterial communities from 11 super-shedders and 11
      contemporary pen mates negative for E. coli O157:H7. The dataset was analyzed by
      using five independent clustering methods to minimize potential biases and to
      increase confidence in the results. Our analyses collectively indicated
      significant variations in microbiome composition between super-shedding and non
      shedding cattle. Super-shedders exhibited higher bacterial richness and diversity
      than non-shedders. Furthermore, seventy-two operational taxonomic units, mostly
      belonging to Firmicutes and Bacteroidetes phyla, were identified showing
      differential abundance between these two groups of cattle. The operational
      taxonomic unit affiliation provides new insight into bacterial populations that
      are present in feces arising from super-shedders of E. coli O157:H7. 

PMID- 24858733
TI  - Does distress intolerance moderate the link between ADHD symptoms and number of
      sexual partners?
AB  - Previous research demonstrates that ADHD symptoms are related to increased risky
      sexual behavior. Distress intolerance (DIT) has also been linked to risk behavior
      and may also be related to increased risky sexual behavior. Thus, we evaluated
      the degree to which DIT moderated the link between ADHD symptoms and number of
      casual and monogamous sexual partners. Participants were undergraduate psychology
      students (N = 660; 30 % male; M = 20.23, SD = 1.40; 47 % European American) who
      completed an online assessment. Hierarchical multiple regression revealed that
      several DIT constructs, specifically tolerance, appraisal, and regulation,
      moderated the link between ADHD symptoms and casual sex partners. Only regulation
      moderated the association between ADHD symptoms and monogamous sex partners.
      Results suggest that difficulty managing distress moderates the link between ADHD
      symptoms and number of sexual partners. These results have important implications
      for prevention and intervention program development. 

PMID- 24858734
TI  - Higher body mass index may be a predictor of extrathyroidal extension in patients
      with papillary thyroid microcarcinoma.
AB  - Recently, higher body mass index (BMI) has been associated with aggressive
      pathologic features of papillary thyroid carcinoma. The aim of this study was to
      clarify the relationship between BMI and aggressive pathologic features of
      papillary thyroid microcarcinoma (PTMC) and to evaluate whether the BMI can be a
      prognostic factor of PTMC. This retrospective study included 612 PTMC patients
      who underwent surgical excision at a referral center between April 2006 and
      December 2007. Patients were grouped according to BMI (<25 or >=25 kg/m2).
      Multivariable logistic regression analysis was performed to determine independent
      predictors of aggressive pathologic features (advanced stage, extrathyroidal
      extension, and lymph node metastasis), with adjustment for age, gender, tumor
      size, multifocality, thyroid stimulating hormone (TSH) level, and BMI
      (value/group). PTMC patients with a BMI>=25 kg/m2 showed significantly higher
      prevalences of extrathyroidal extension, advanced pathologic TNM stage, and male
      gender, compared to those of patients with a BMI<25 kg/m2. Lymph node metastasis
      and mean TSH level were not significantly different between the two BMI
      subgroups. In multivariable analysis, the BMI>=25 kg/m2 group was positively
      associated with the presence of extrathyroidal extension (adjusted odds ratio
      1.49, P=0.05). Higher BMI was associated with extrathyroidal extension in PTMC
      patients. This study suggests that the BMI could be considered as a prognostic
      factor for predicting the presence of extrathyroidal extension and it may help
      decide the appropriate surgical extent for PTMC patients.

PMID- 24858735
TI  - Identification of risk conditions for the development of adrenal disorders: how
      optimized PubMed search strategies makes the difference.
AB  - The exponential growth of scientific literature available through electronic
      databases (namely PubMed) has increased the chance of finding interesting
      articles. At the same time, search has become more complicated, time consuming,
      and at risk of missing important information. Therefore, optimized strategies
      have to be adopted to maximize searching impact. The aim of this study was to
      formulate efficient strings to search PubMed for etiologic associations between
      adrenal disorders (ADs) and other conditions. A comprehensive list of terms
      identifying endogenous conditions primarily affecting adrenals was compiled. An
      ad hoc analysis was performed to find the best way to express each term in order
      to find the highest number of potentially pertinent articles in PubMed. A
      predefined number of retrieved abstracts were read to assess their association
      with ADs' etiology. A more sensitive (providing the largest literature coverage)
      and a more specific (including only those terms retrieving >40 % of potentially
      pertinent articles) string were formulated. Various researches were performed to
      assess strings' ability to identify articles of interest in comparison with non
      optimized literature searches. We formulated optimized, ready applicable tools
      for the identification of the literature assessing etiologic associations in the
      field of ADs using PubMed, and demonstrated the advantages deriving from their
      application. Detailed description of the methodological process is also provided,
      so that this work can easily be translated to other fields of practice.

PMID- 24858736
TI  - Selenium supplementation and the risk of type 2 diabetes mellitus: a meta
      analysis of randomized controlled trials.
AB  - It is well documented that selenium (Se) is involved in the metabolism of
      glucose. However, whether Se supplementation could lower the risk of type 2
      diabetes mellitus (T2DM) remains elusive. We aimed to evaluate the association
      between Se supplementation and the risk of T2DM by performing a meta-analysis. We
      searched the Pubmed, Embase, and Cochrane databases from January 1990 to November
      2013 to identify randomized controlled trials (RCTs) that met pre-stated
      inclusion criteria. Reference lists of retrieved articles were also reviewed.
      Either a fixed-effects or, in the presence of heterogeneity, a random-effects
      model was used to calculate the pooled prevention effects. Four RCTs involving
      20,294 participants were included in this meta-analysis. The combined relative
      risks (RRs) for subjects administered with Se compared with control groups were
      1.09 (95 % CI: 0.99-1.20, p = 0.085). Omission of any single study did not change
      the overall risk estimates significantly. Meta- regression analyses showed almost
      no impact on the RRs of age and study length. No evidence of publication bias was
      observed. In conclusion, our findings do not support the routine application of
      Se supplementation for T2DM prevention in Caucasians. Larger studies are needed
      to investigate the effects of Se supplementation on T2DM prevention among various
      populations and further elucidate the impact of age and study length.

PMID- 24858737
TI  - Low-power fractional CO2 laser versus low-fluence Q-switch 1,064 nm Nd:YAG laser
      for treatment of melasma: a randomized, controlled, split-face study.
AB  - BACKGROUND: Various laser treatments are currently available for melasma but
      their use remains challenging because of potential side effects. OBJECTIVE: The
      aim of this randomized controlled study was to compare the efficacy and safety of
      low-fluence Q-switch 1,064 nm Nd:YAG and low-power fractional CO2 laser using a
      split-face design. MATERIALS AND METHODS: A total of 40 female patients with
      symmetric melasma were enrolled to the study and each side of their face was
      randomly allocated to either low-fluence Q-switch 1,064 nm Nd:YAG or low-power
      fractional CO2 laser. They were treated every 3 weeks for five consecutive
      sessions and followed for 2 months after the last treatment session. Response to
      treatment was assessed using the Melanin Index (MI) score, modified Melasma Area
      and Severity Index (mMASI) score, and a subjective self-assessment method.
      RESULTS: At the 2-month follow-up visit, both sides of the face had statistically
      significant reductions in the MI and mMASI scores compared with the first visit
      (p < 0.001). The differences between the mean MI and mMASI scores at baseline and
      at 2-month follow-up were compared between the two treatments and results showed
      that the reduction of MI and mMASI score in the fractional CO2 laser-treated side
      was significantly more than on the Q-switch 1,064 nm Nd:YAG laser-treated side (p
      < 0.001). There were no significant adverse effects with either of the laser
      treatments. CONCLUSION: The present study shows that low-power fractional CO2
      laser is safe and effective and can be considered as a valuable approach in the
      treatment of melasma.

PMID- 24858738
TI  - Symptom clusters predict mortality among dialysis patients in Norway: a
      prospective observational cohort study.
AB  - CONTEXT: Patients with end-stage renal disease on dialysis have reduced survival
      rates compared with the general population. Symptoms are frequent in dialysis
      patients, and a symptom cluster is defined as two or more related co-occurring
      symptoms. OBJECTIVES: The aim of this study was to explore the associations
      between symptom clusters and mortality in dialysis patients. METHODS: In a
      prospective observational cohort study of dialysis patients (n = 301), Kidney
      Disease and Quality of Life Short Form and Beck Depression Inventory
      questionnaires were administered. To generate symptom clusters, principal
      component analysis with varimax rotation was used on 11 kidney-specific self
      reported physical symptoms. A Beck Depression Inventory score of 16 or greater
      was defined as clinically significant depressive symptoms. Physical and mental
      component summary scores were generated from Short Form-36. Multivariate Cox
      regression analysis was used for the survival analysis, Kaplan-Meier curves and
      log-rank statistics were applied to compare survival rates between the groups.
      RESULTS: Three different symptom clusters were identified; one included loading
      of several uremic symptoms. In multivariate analyses and after adjustment for
      health-related quality of life and depressive symptoms, the worst perceived
      quartile of the "uremic" symptom cluster independently predicted all-cause
      mortality (hazard ratio 2.47, 95% CI 1.44-4.22, P = 0.001) compared with the
      other quartiles during a follow-up period that ranged from four to 52 months. The
      two other symptom clusters ("neuromuscular" and "skin") or the individual
      symptoms did not predict mortality. CONCLUSION: Clustering of uremic symptoms
      predicted mortality. Assessing co-occurring symptoms rather than single symptoms
      may help to identify dialysis patients at high risk for mortality.

PMID- 24858739
TI  - Symptom burden of cancer patients: validation of the German M. D. Anderson
      Symptom Inventory: a cross-sectional multicenter study.
AB  - CONTEXT: Cancer patients frequently suffer from various symptoms often impairing
      functional status and quality of life. To enable timely supportive care, these
      symptoms must be assessed adequately with reliable tools. OBJECTIVES: This study
      aimed to validate the German version of the M. D. Anderson Symptom Inventory
      (MDASI). METHODS: This was a multicenter, cross-sectional, observational study.
      At five German university hospitals, 697 cancer patients aged from 18 to 80 years
      undergoing active anticancer treatment were recruited to participate in the
      study. For the validation, reliability (Cronbach's alpha), construct validity
      (factor analysis), known group validity (Eastern Cooperative Oncology Group
      Performance Status), and convergent divergent analyses were calculated. RESULTS:
      Of the 980 patients who were eligible, 697 patients were included and agreed to
      participate in the study (71%). Reliability analysis showed good internal
      consistencies for the MDASI set of symptoms (Cronbach's alpha coefficient = 0.82;
      95% CI = 0.78, 0.84) and for the set of interference items (Cronbach's alpha
      coefficient = 0.857; 95% CI = 0.484, 0.87). Factor analysis resulted in a one
      factor solution (general symptoms; eigenvalue = 4.26) with a psychological
      (distress and sadness) and a gastrointestinal subscale (nausea and vomiting).
      Convergent and divergent analyses showed significant correlations between symptom
      burden and distress and global health-related quality of life (subscale of the
      European Organization for Research and Treatment of Cancer Quality of Life
      Questionnaire-C30 Version 3.0.). CONCLUSION: The MDASI-German version is a valid
      tool for measuring patient-reported symptom severity and symptom interference in
      German cancer patients. It is easily applicable and can be used by German
      clinicians and researchers for screening and monitoring purposes and the
      comparison of international data.

PMID- 24858740
TI  - Validation of a measure of family experience of patients with serious illness:
      the QUAL-E (Fam).
AB  - CONTEXT: Family members of seriously ill patients experience significant burden
      as they advocate with providers and participate in key decisions for loved ones.
      Most assessments focus on patient experience, yet family members' own quality of
      experience is central to comprehensive care. OBJECTIVES: This study validated a
      measure of the quality of family experience, the QUAL-E (Fam), in palliative
      care. METHODS: We enrolled family members of terminally ill patients admitted to
      general medicine services at two hospitals. Items were based on foundational work
      originally done for the patient instrument, QUAL-E, and interviews of family
      members of terminally ill patients. Cognitive interviewing was used to refine
      items, which then underwent formal testing factor analysis. In the first sample,
      we assessed factor structure. A subsequent sample established predictive validity
      and test-retest reliability. RESULTS: The initial item pool was reduced to a four
      domain, 35-item scale and administered to the validation sample. Further analyses
      produced a final brief scale comprising 17 items, demonstrating appropriate
      convergent and divergent validity. Test-retest reliability demonstrated expected
      levels of stability in a highly changeable population. The scale provides an
      assessment of family experience and includes subscales assessing relationship
      with health care provider and completion. Additional scale items assess symptom
      experience and issues of preparation. CONCLUSION: The QUAL-E (Fam) is a companion
      instrument to the patient QUAL-E measure of quality of life at the end of life
      and is part of a package of assessment tools that can help evaluate the entire
      patient experience and contribute to quality care.

PMID- 24858741
TI  - Assessment of gingival mucosa of infant rats during teething.
AB  - AIM: The aim of the present study was to perform a histological analysis of the
      gingival mucosa in infant rats undergoing the teething process. MATERIALS AND
      METHODS: Eighteen Wistar rats between 8 and 15 days of life were distributed
      among three groups: group A--without teething; group B--eruption of incisors; and
      group C--eruption of incisors and molars. The samples included teeth and
      periodontal tissue from the region of the incisors and molars of each animal.
      Fragments were processed for histological analysis and submitted to
      immunohistochemical analysis. RESULTS: In the 8-day-old rats, mild inflammatory
      infiltrate predominated with mononuclear cells in the pericoronal follicles of
      the incisors and molars. At 12 days of age, all animals exhibited moderate
      inflammation in the pericoronal follicles and epithelium of the incisors and mild
      inflammatory infiltrate with predominantly mononuclear cells in the molars. At 15
      days of age, moderate neutrophilic exudate was found in the pericoronal follicles
      and epithelium of the incisors and molars. Immunohistochemical analysis revealed
      positivity for interleukin- 1b in the pericoronal follicles in the pre-eruption
      phase. CONCLUSION: An inflammatory reaction with progressive intensity occurs
      during the teething process, the response of which is preceded by the release of
      interleukin-1b. CLINICAL SIGNIFICANCE: Morphological proof of events that occur
      during teething that can affect the dynamics of the physiologic process
      manifesting as clinical symptoms.

PMID- 24858742
TI  - The antibacterial properties of composite resin containing nanosilver against
      Streptococcus mutans and Lactobacillus.
AB  - AIM: The aim was to evaluate the antibacterial properties of composite resin
      containing nanosilver against Streptococcus mutans (SM) and Lactobacillus (L).
      MATERIALS AND METHODS: Nanosilver was added to Z250 composite at 0.5 and 1% by
      weight. In order to confirm the homogenous distribution of the nanoparticles in
      the composite resin, SEM-EDX analysis was performed on one sample in each group.
      Z250 composite without nanosilver was used as control. Direct contact test was
      used to test the antibacterial properties of nanoparticle-loaded composites:
      0.001 ml of 0.5 Mc Farland suspension of MS and L was placed on composite disks,
      and incubated for 1 hour in 5 to 10% CO2 incubator at 37 degrees C. Samples were
      placed in 0.5 ml of sterile BHI broth and incubated for 2 hours in CO2 incubator.
      Afterwards, 0.001 ml liquid from each medium was distributed on blood agar plates
      and incubated for 48 hours in CO2 incubator. The numbers of bacterial colonies
      were counted visually. Data were analyzed using Two-way ANOVA and Tukey HSD test.
      Significance level was set at 0.05. RESULTS: Addition of nanosilver to composite
      resin had a significant effect on reduction of the number of SM and L colonies (p
      = 0.000). The antibacterial properties of composite resins are different
      depending on the concentration of nanosilver (p = 0.014). Tukey test indicated
      that increase in the concentration of nanosilver caused the increase in
      antibacterial properties of composite resin. CONCLUSION: Addition of silver
      nanoparticles to Z250 composite could significantly inhibit the growth of
      Streptococcus mutans and Lactobacillus on the surface of this composite. CLINICAL
      SIGNIFICANCE: The addition of nanosilver to Z250 composite could inhibit the
      growth of SM and L on the surface of the restoration and therefore prevent the
      occurrence of secondary caries.

PMID- 24858743
TI  - MM-MTA for direct pulp capping: a histologic comparison with ProRoot MTA in rat
      molars.
AB  - AIM: To compare the histomorphological response of rat dental pulps capped with
      MM-MTA and ProRoot MTA at 1, 2 and 4 weeks postoperatively. MATERIALS AND
      METHODS: Direct pulp capping with MM-MTA and ProRoot MTA, overlaid with light
      cured composite resin, was performed on right and left maxillary first molars of
      20 Wistar rats. Animals were killed at 1, 2 and 4 weeks postoperatively. Biopsy
      samples were stained and viewed by light microscopy to determine dentin bridge
      formation. Data were statistically evaluated with the Kruskal-Wallis test (p <
      0.05). RESULTS: Absence of dentin bridge formation at 1 week, partial dentin
      bridge formation at 2 weeks and complete dentin bridge formation at 4 weeks are
      observed with MM-MTA and ProRoot MTA. The results showed no statistically
      significant difference between both materials at 4 weeks. CONCLUSION: Both
      materials produced similar responses in the pulp when used for pulp capping in
      intact, caries-free molars of rats.

PMID- 24858744
TI  - Radiation risk assessment in professionals working in dental radiology area using
      buccal micronucleus cytome assay.
AB  - OBJECTIVE: The aim of this study was to assess the incidence of micronuclei (MN)
      in buccal mucosal cells of professionals working in radiology area to determine
      the risk of stochastic effects of radiation. MATERIALS AND METHODS: All the
      professionals and students working in King Khalid University - College of
      Dentistry radiology area were included in the Risk Group (RG = 27). The Control
      Group (CG = 27) comprised of healthy individual matching the gender and age of
      the RG. Buccal mucosal scraping from all the 54 subjects of RG and CG were
      stained with Papanicolaou stain and observed under oil immersion lens (*100) for
      the presence of micronuclei (MN) in the exfoliated epithelial cells. RESULTS:
      There was no significant difference between the incidence of MN in RG and CG (p =
      >0.05) using t-test. CONCLUSION: Routine radiation protection protocol does
      minimize the risk of radiation induced cytotoxicity, however, screening of
      professionals should be carried out at regular intervals.

PMID- 24858745
TI  - A comparative evaluation of cleaning efficacy (debris and smear layer removal) of
      hand and two NiTi rotary instrumentation systems (K3 and ProTaper): a SEM study.
AB  - OBJECTIVES: The present study was conducted to compare the cleaning efficacy
      (debris and smear layer removal) of hand and two NiTi rotary instrumentation
      systems (K3 and ProTaper). MATERIALS AND METHODS: Sixty single rooted human
      maxillary anterior teeth decoronated at the cementoenamel junction were used. All
      the specimens were divided into four groups of 15 teeth each, group I--ProTaper
      rotary instrumentation done, group II--K3 rotary instrumentation done, group III-
      Stainless steel K-file instrumentation done, group IV--root canal irrigation
      without instrumentation. Root canal preparation was done in a crown down manner
      and 3% sodium hypochlorite was used as irrigant after each file followed by final
      rinse with 5 ml of 17% EDTA solution, then specimens were scanning electron
      microscopic (SEM) examination. RESULTS: Statistical analysis was done using one
      way ANOVA followed by post hoc Tukey's HSD test. Group I showed highly
      statistical significant difference compared to other groups. There was no
      statistically significant difference considering smear layer at any levels among
      the groups with no smear layer formation in group IV. CONCLUSION: ProTaper rotary
      instrumentation showed the maximum cleaning efficacy followed by K3 rotary
      instrumentation in the coronal, middle and apical thirds of the root canal.
      CLINICAL SIGNIFICANCE: ProTaper rotary instruments are more efficient than hand
      and K3 rotary instruments during root canal treatment.

PMID- 24858746
TI  - An evaluation of shear bond strength of self-etch adhesive on pre-etched enamel:
      an in vitro study.
AB  - AIM: To determine the shear bond strength of self-etch adhesive G-bond on pre
      etched enamel. MATERIALS AND METHODS: Thirty caries free human mandibular
      premolars extracted for orthodontic purpose were used for the study. Occlusal
      surfaces of all the teeth were flattened with diamond bur and a silicon carbide
      paper was used for surface smoothening. The thirty samples were randomly grouped
      into three groups. Three different etch systems were used for the composite build
      up: group 1 (G-bond self-etch adhesive system), group 2 (G-bond) and group 3
      (Adper single bond). Light cured was applied for 10 seconds with a LED unit for
      composite buildup on the occlusal surface of each tooth with 8 millimeters (mm)
      in diameter and 3 mm in thickness. The specimens in each group were tested in
      shear mode using a knife-edge testing apparatus in a universal testing machine
      across head speed of 1 mm/ minute. Shear bond strength values in Mpa were
      calculated from the peak load at failure divided by the specimen surface area.
      The mean shear bond strength of all the groups were calculated and statistical
      analysis was carried out using one-way Analysis of Variance (ANOVA). RESULTS: The
      mean bond strength of group 1 is 15.5 Mpa, group 2 is 19.5 Mpa and group 3 is
      20.1 Mpa. Statistical analysis was carried out between the groups using one-way
      ANOVA. Group 1 showed statistically significant lower bond strength when compared
      to groups 2 and 3. No statistical significant difference between groups 2 and 3
      (p < 0.05). CONCLUSION: Self-etch adhesive G-bond showed increase in shear bond
      strength on pre-etched enamel.

PMID- 24858747
TI  - Evaluation of effectiveness of chemical disinfectants in reducing bacterial
      growth on orthodontic instruments.
AB  - Infection control requires serious effort in all fields of dentistry including
      orthodontics. Though there are various means of sterilization and disinfection in
      dental office, chemical disinfection is the most preferred method among
      orthodontists. The purpose of this study is to evaluate different chemical
      sterilization and disinfection methods used in orthodontic offices, which would
      guide the orthodontists in infection control.

PMID- 24858748
TI  - Influence of nicotine and cotinine impregnation on the first step of periodontal
      regeneration: clot stabilization.
AB  - This study analyzes the clot stabilization on root surfaces of teeth impregnated
      with cotinine and nicotine and the influence of the scaling in the adhesion of
      blood components, observing the influence of new exposition to nicotine and/or
      cotinine after scaling. Fifteen human teeth extracted due to periodontal disease
      of non-smokers patients were selected and manually scaled. Four dentin blocks
      were obtained from each tooth (n = 60). Samples received blood application or
      reimpregnation with nicotine and/or cotinine, depending on the groups. Group 1:
      PBS immersion + root scaling + blood; group 2: nicotine + root scaling + blood;
      group 3: nicotine + root scaling + nicotine reapplication + blood; group 4:
      cotinine + root scaling + blood; group 5: cotinine + root scaling + cotinine
      reapplication+ blood; group 6: nicotine and cotinine + root scaling + nicotine
      and cotinine + blood. Samples were kept in 2 ml of each substance for 24 hours.
      Each group received a blood drop and was analyzed by SEM. The higher amount of
      blood components was present in teeth exposed to cotinine and the groups
      submitted to scaling and blood application in comparison with groups that
      received reapplication of toxic substances after scaling. The greater toxic
      effect on root dentin surface was after the exposure to nicotine and cotinine.
      Results suggest that periodontal healing may be delayed in smokers due to the
      direct inhibition of clot stabilization on the root surface when nicotine and
      cotinine are present concomitantly.

PMID- 24858749
TI  - In vitro retention loss of attachment-retained removable partial denture.
AB  - AIM: To investigate the importance of attachment types on the retention loss of
      extracoronal attachment-retained removable partial dentures depending on the
      usage period. MATERIALS AND METHODS: In order to observe the retention loss of 5
      different attachments (OT Strategy, OT Strategy-metal protected, Vario-stud-snap
      and Vario-soft 3 and ERA-RV) over time, attachment-retained partial dentures
      representing Kennedy II mod. I case were placed in a custom-made, retention test
      machine. For each minute, eight separating and joining movements were performed
      and retention values (Newton) of the attachments were recorded by computer. The
      retention tests implemented in 540,1080 and 2160 cycles. The data were evaluated
      statistically according to the two-way ANOVA and Tukey parametrical tests.
      RESULTS: The slide type attachment providing the best retention force was
      observed to be the most worn out by this process (p < 0.01) while the ball type
      attachments, which typically have the lesser retention force, showed less
      retention loss (p < 0.01). CONCLUSION: It can be concluded that the retention
      attributes of the attachment-retained dentures were affected by the specific type
      of precision attachment as well as the usage period. CLINICAL SIGNIFICANCE:
      Precision attachments with ball-type plastic matrices may be recommended for the
      clinical use due to their retention stability over time.

PMID- 24858750
TI  - Effect of lycopene in the treatment of periodontal disease: a clinical study.
AB  - PURPOSE: Several epidemiologic studies have suggested a role of tomato products
      in decreasing the risk of the development of diseases related to oxidative stress
      (cancer and other chronic diseases). Oxidative stress may result in periodontal
      tissue damage either directly or indirectly. Lycopene, a powerful antioxidant and
      the main carotenoid in tomato products possesses the greatest quenching ability
      of singlet oxygen among the various carotenoids and is effective in protecting
      blood lymphocytes from NOO-radical damage. Hence, the aim of the present study is
      to compare the effect of systemically administered lycopene as an adjunct to
      scaling and root planing in patients with gingivitis and periodontitis. MATERIALS
      AND METHODS: Twenty systemically healthy patients were involved in a randomized,
      double-blind, parallel study and based on their clinical signs were divided into
      two groups of mild to moderate periodontitis (A) and moderate gingivitis (B). The
      subjects under the groups A and B were randomly distributed between the two
      treatment groups: test group (n = 5), 4 mg lycopene/day for 2 weeks with oral
      prophylaxis (full mouth scaling and root planing (SRP) completed within 24 hours)
      and controls (n = 5), receiving only oral prophylaxis. Pre- and post-therapeutic
      periodontal parameters were evaluated. RESULTS: In group A, statistically
      significant improvement in CAL was reported in test group as compared to control
      group. In group B, the difference between pretreatment and post-treatment
      bleeding on probing scores was found to be statistically non-significant in both
      groups. CONCLUSION: Results show that lycopene is a promising treatment modality
      as an adjunct to full mouth SRP of the oral cavity in patients with moderate
      periodontal disease. CLINICAL SIGNIFICANCE: Modulation of the free radical
      production seems to be essential for the inhibition of tissue destruction, and
      treatment with antioxidants, like lycopene, which is the most potent among them
      will block the production of free ROS or its effects might prove to be
      therapeutically valuable.

PMID- 24858751
TI  - Direct measurement of stain retention in third molars.
AB  - AIM: To directly determine the mass of dye retained in teeth following exposure
      to aqueous solutions of Rhodamine B and to correlate tooth color modifications.
      MATERIALS AND METHODS: Extracted third molars (25) were selected and sectioned at
      the cementoenamel junction for coronal staining. Pulp tissue was removed and
      teeth sonicated to remove debris. Teeth were kept in deionized water for 12 hours
      and subsequently weighed. They were then stained for 4 hours in 5 ml of Rhodamine
      B dye at two different concentrations. The samples were then subjected to two 8
      hours rinses in deionized water. The tooth shade was recorded with a commercially
      available intraoral spectrophotometer (Vita Easyshade Compact, Vita Zahnfabrik,
      Bad Sackingen, Germany) at baseline (T1), after dye immersion (T2), and after
      water rinsing (T3). A standard absorption curve was then used to calculate the
      dye mass in the rinse solutions as well as the post- treatment stain solutions.
      All solution optical absorption curves were recorded using a laboratory research
      spectrophotometer (Cary 300, Agilent, USA). The mass of dye in each solution was
      then calculated from the standard curve relating optical absorption to aqueous
      dye concentration. RESULTS: An average change in the CIE (a) values of 8.0 +/-
      0.3 were observed for concentrations of Rhodamine B similar to the optical
      appearance of wine or other darkly colored juices while an increase of 10* in
      concentration gave values too high to measure using a standard intraoral
      spectrophotometer. By measuring the optical absorbance of the staining solutions
      before and after the staining process, we were able to measure dye retention of
      54 +/- 26 micrograms per gram of tooth. CONCLUSION: While no significant
      correlation could be found between the amount of stain retention in the dentition
      and the tooth shade due to the high uncertainties in the spectroscopic
      measurements, we were able to show that this method should admit such comparisons
      for future research. CLINICAL SIGNIFICANCE: The development of a reliable
      chromophore infiltration model may provide standardized and reproducible results
      in evaluating tooth whitening efficacy.

PMID- 24858752
TI  - Quantitative evaluation of apical extrusion of debris and irrigants using four
      rotary instrumentation systems: an in vitro study.
AB  - CLINICAL SIGNIFICANCE: The apical extrusion of infected debris may have the
      potential to disrupt the balance between microbial aggression and host defense,
      resulting in incidents of acute inflammation. During preparation, irrigants and
      debris, such as bacteria, dentin filings and necrotic tissue may be extruded into
      the periradicular region leading to periapical inflammation and postoperative
      flare ups. Using an instrumentation technique that minimizes apical extrusion
      would be beneficial to both the practitioner and patient. The purpose of the
      study was to evaluate the weight of debris and volume of irrigant extruded
      apically from extracted teeth in vitro after endodontic instrumentation using
      four different rotary root canal instrumentation systems. MATERIALS AND METHODS:
      Four groups of each 20 extracted mandibular premolars were instrumented using one
      of the four systems: ProTaper Universal (Dentsply Maillefer, Ballaigues,
      Switzerland)), Hero-shaper (MicroMega, Besancon, France), RaCe (FKG Dentaire, La
      Chaux-de-Fonds, Switzerland) and K3 (SybronEndo, West Collins, CA). Debris and
      irrigant extruded from the apical foramen during instrumentation were collected
      in preweighed test tubes. Volume of irrigant extruded was noted. The containers
      were stored in incubator at 70 degrees  for two days to evaporate the moisture.
      Weight of dry debris was noted. STATISTICAL ANALYSIS: Data was analyzed using
      Kruskall-Wallis and Mann-Whitney U test at a significance of 0.001. RESULTS: The
      results indicated that all of the instrumentation systems tested caused
      measurable apical extrusion of debris and irrigants. Higher extrusion was
      observed with Protaper system which was statistically significant with Hero
      Shaper, RaCe and K3 systems. There were no statistical differences between Hero
      shaper, K3 and RaCe systems (p < 0.05). CONCLUSION: All instrumentation
      techniques apically extruded debris and irrigant. However, Hero-shaper, K3 and
      RaCe systems produced less extruded debris and irrigant than the Protaper system.

PMID- 24858753
TI  - Fiber technology in space maintainer: a clinical follow-up study.
AB  - Various space maintainers are used in pediatric dentistry. However, their
      construction requires time consuming laboratory procedures. Recently fiber
      reinforced composite resin (FRCR) has been introduced for various application in
      dentistry. Polyethylene fibers appear to have the best properties in elasticity,
      translucency, adaptability, tenaciousness, resistance to traction and to impact.
      The purpose of this study was to clinically evaluate the long-term effect of FRCR
      space maintainer made with Ribbond((r)) bondable reinforcement ribbon in children
      over a period of 18 months. A total of thirty FRCR space maintainers were applied
      to 30 children between the age group of 6 to 9 years old, follow-up visits were
      done at 1, 6, 12 and 18 months. The data obtained was subjected to statistical
      analysis. Maxillary appliances survived more than mandibular appliances. Mean
      survival time of space maintainer were found to be 12 months (minimum 1 and
      maximum 18 months). The present study suggested that FRCR space maintainers
      (Ribbond((r))), which was observed for up to 18 months, can be accepted as a
      successful alternative to conventional band-loop space maintainer only for short
      periods.

PMID- 24858754
TI  - Biomechanical characteristics of microimplant for anchorage in orthodontics: a 3D
      finite element model study.
AB  - In orthodontic treatment, anchorage control is essential for success. A recent
      development, stationary anchorage (micro- implants) eliminates one of the
      uncertainties of orthodontic tooth movement by offering absolute control over
      potentially undesirable counter movements. The objective of this study was to
      establish a 3D finite element model for microimplant and to analyze the influence
      of different angulations to the long axis of the teeth (30-90 degrees ) on the
      biomechanical characteristics of orthodontic anchorage implant-bone interface.
      Results of this study showed that largest stress and deformation was seen in the
      cortical bone and upper region of trabecular bone. Stress and deformation
      increased as the angulations of the implant to the long axis of the tooth
      increased. As the angulation of the implant to the long axis of maxillary 1st
      molar increased, stress and deformation also decreased. Maximum stress and
      displacement were recorded when implant was placed perpendicular to the long axis
      of maxillary 1st molar.

PMID- 24858755
TI  - The use of controlled release locally delivered 10% doxycycline hyclate gel as an
      adjunct to scaling and root planing in the treatment of chronic periodontitis:
      clinical and microbiological results.
AB  - BACKGROUND: Local delivery of antimicrobial agents provides higher concentration
      of the drug in the periodontal site for longer periods than systemically
      delivered methods. In the present study an attempt is made to know the efficacy
      of controlled local drug delivery of doxycycline as an adjunctive treatment in
      the management of chronic periodontitis. MATERIALS AND METHODS: A total of 12
      patients, diagnosed as Chronic Periodontitis in the age of 25 to 55 years, were
      selected of both the sexes in this study. They were divided into Experimental
      group consisted of 30 sites who received complete scaling and root planing (SRP)
      followed by placement of Atridox gel and control group consisted of 30 sites who
      received only SRP. Clinical parameters were recorded at, baseline, days 30, 90
      and 180. Parameters were plaque index, gingival index, gingival bleeding index
      and microbial analysis, probing pocket depth and Clinical attachment level (CAL).
      The microbiological analysis was done at baseline visit and at 90th day. Probing
      pocket depth and CAL were recorded only on day 0 and 180th day. RESULTS: In 180
      days study, both the groups exhibited a significant improvement in periodontal
      status. Significant gain in attachment level was observed in both the group.
      Between both the groups the clinical parameters in the experimental groups
      exhibited better results as compared to the control group. Both the groups
      exhibited significant reduction in the number of spirochetes. CONCLUSION:
      Combination therapy of SRP and 10% DH gel demonstrated better results at all
      levels suggesting that this therapy can play a significant role as an adjunct to
      SRP in the management of chronic periodontitis.

PMID- 24858756
TI  - Effects of bimax and segmental surgeries for correction of bimaxillary
      dentoalveolar protrusion class I on soft tissue parameters: upper lip thickness
      and curvature, nasolabial angle and nasal prominence.
AB  - AIM: Results of this study can show if bimax surgery for posterior repositioning
      of maxilla and correction of BPCLI has priority to the currently used segmental
      orthognathic surgery or not. MATERIALS AND METHODS: This study was done on 40
      white- skinned Iranian patients with bimaxillary dentoalveolar protrusion class I
      (BPCLI) who sought treatment for their deformity. In the first group, treatment
      includes segmental surgery for backward replacement of anterior segment of the
      upper and lower jaw. In the second group, treatment was bimax surgery, in which
      whole upper and lower jaw moved backward. Twenty patients were included in each
      group. For this purpose, we measured upper lip thickness (ULT, distance between
      LS and IA), nose prominence (NP, distance between nasal tip and the perpendicular
      line from upper lip vermilion on FHP), subsulcus depth (SSD, distance of SLS from
      this perpendicular line), SN to H line distance and finally, nasolabial angle
      (NLA) before and after surgery. RESULTS: In our study, 65% of patients were
      female and the mean of age was 27 (17-39) years old. The mean of SNA, SNB, ANB
      and INA in our patients were 81.7 +/- 2.9, 78.8 +/- 2.8, 4.50 +/- 1.4 and 120 +/-
      8.7, respectively. All variables except SSD were analyzed with t-test to compare
      the results of two methods of surgery. Differences in the values of NP, NLA, SN
      to H line distance and ULT before and after segmental and bimax surgeries between
      before and after surgery were significant. After surgeries, ULT and the SN to H
      line distance reduced significantly, and NLA became corrected to its normal range
      (90-110). CONCLUSION: The results of this study showed that bimax and segmental
      surgeries can effectively correct BPCLI. Because of possible dental and
      periodontal complications of segmental surgery, we highly recommend bimax surgery
      for treatment of BPCLI.

PMID- 24858757
TI  - Evaluation of the physicochemical properties and push-out bond strength of MTA
      based root canal cement.
AB  - AIM: This study investigated the flowability, setting time, pH, calcium release
      and bond strength of a MTA-based cement (MTA Fillapex((r))) compared to AH Plus
      and Sealapex. MATERIALS AND METHODS: For the flowability test, the ISO 6876:2001
      specification was utilized and for the setting time test, the ASTM C266-03
      specification was utilized. For the pH and calcium release measurements, 10
      samples were prepared for each group and analyzed for several different periods.
      For the push-out test, dentin disks were distributed into three groups, according
      to the cement utilized and into three subgroups, according to the root third (n =
      10). After obturation, the specimens underwent push-out testing. The data were
      compared statistically using a significance level of 5%. RESULTS: The flowability
      of all materials was found to be similar (p > 0.05). The setting times were
      different among the groups tested (MTA Fillapex < Sealapex < AH Plus) (p < 0.05).
      At days 7 and 28, the MTA Fillapex presented the higher pH values (p < 0.05). At
      24 hours and at 14 days, the calcium release of the MTA Fillapex was similar to
      that of Sealapex (p > 0.05). AH Plus presented the lowest pH and calcium release
      values (p < 0.05). In all root thirds, the adhesion to the dentin of the MTA
      Fillapex and Sealapex were significantly lower than that of AH Plus (p < 0.05).
      CONCLUSION: MTA Fillapex and Sealapex presented several similar properties and
      both were found to be different than AH Plus. CLINICAL SIGNIFICANCE: This study
      evaluated the physicochemical and mechanical properties of new MTA-based root
      canal cement, in order to use this scaler in root canal fillings. MTA Fillapex
      showed satisfactory properties for clinical use.

PMID- 24858758
TI  - Influence of disinfection with peracetic acid and hypochlorite in dimensional
      alterations of casts obtained from addition silicone and polyether impressions.
AB  - Dental impressions disinfection is important to reduce the risk of cross
      contamination but this process may produce dimensional distortions. Peracetic
      acid is a disinfectant agent with several favorable characteristics yet
      underutilized in Dentistry. The aim of this paper is to compare the dimensional
      stability of casts obtained from addition silicone and polyether impressions that
      were immersed for 10 minutes in a solution of 0.2% peracetic acid or 1% sodium
      hypochlorite. Sixty samples in type IV gypsum were produced after a master cast
      that simulated a full crown preparation of a maxillary premolar. Samples were
      divided in 6 groups (n = 10) according to the impression material and
      disinfection agent: Group AC--addition silicone control (without disinfectant);
      Group APA--addition silicone + 0.2% peracetic acid; Group AH--addition silicone +
      1% sodium hypochlorite; Group PC--polyether control (without disinfectant); Group
      PPA--polyether + 0.2% peracetic acid; Group PH--polyether + 1% sodium
      hypochlorite. Cast height, base and top diameter were measured and a mean value
      was obtained for each sample and group all data was statistically analyzed
      (ANOVA, p < 0.05). There was not a significant statistical difference between
      addition silicone and polyether impressions regardless of the disinfectant
      materials. It can be concluded that disinfection with the proposed agents did not
      produce significant alterations of the impressions and the peracetic acid could
      be considered a reliable material to disinfect dental molds.

PMID- 24858759
TI  - Effect of a metal primer on the adhesive interface between composite and lingual
      brackets.
AB  - AIM: To test the null hypothesis was that there is no difference in the shear
      strength of indirectly bonded lingual brackets with or without prior application
      of metal primer on their bases. MATERIALS AND METHODS: Forty recently extracted
      human premolars were obtained and randomly divided into two groups of 20 each:
      group I (control), phosphoric acid and indirect bonding with Maximum Cure
      (Reliance Orthodontic Products, Itasca, IL, USA); and group II, application of
      metal primer (Metal Primer, Reliance Orthodontic Products) on bracket base prior
      to conditioning and indirect bonding. All products were used according to the
      manufacturer's instructions. A universal testing machine was used to apply a
      shear force directly onto the enamel- bracket interface at a speed of 1.0 mm/min.
      RESULTS: Mean (SD) shear bond strength for group I was 12.87 (5.75) MPa and for
      the group II was 18.47 (8.48) MPa. The Student's t-test showed a significant
      difference (p = 0.0311) between the groups. The chi-square test for the adhesive
      remnant index (ARI) indicated that there was a significant difference (p =
      0.2750). CONCLUSION: The application of metal primer increased the adhesion of
      lingual brackets, and may be a promising procedure for clinical orthodontics.

PMID- 24858760
TI  - Effect of water storage and additional polymerization on the color parameters of
      flowable resin composites.
AB  - AIMS: Tooth colored dental restorative materials should maintain their chromatic
      properties throughout their service period. The aim of this study was to examine
      the possible color changes of flowable resin composite filling materials
      following water storage. The effect of additional light curing on color stability
      of restorative materials was also investigated. MATERIALS AND METHODS: Six brands
      of light-cured flowable resin composites of the same shade (A3) were prepared
      from two groups generated by curing for 20 or 60 seconds. The initial color
      parameters of the flowable composite samples were measured with a dental
      colorimeter according to the CIELAB color scale, and the samples were stored in
      distilled water at 37 degrees C. Following 2 weeks' water storage, the
      measurements were repeated. The color differences (DeltaE*(ab)) were calculated
      according to the CIELAB formula. Statistical differences between the measurements
      were analyzed by ANOVA and Duncan's tests. RESULTS: No initial color variation
      between the samples cured for 20 seconds and 60 seconds was perceptible
      (DeltaE*(ab)<3.3). However, after 2 weeks' water storage, a noticeable color
      change, DeltaE*(ab)>3.3, was detected in Eco-flow, Filtek Supreme and Grandio
      samples in both polymerization groups. CONCLUSION: Flowable resin composites may
      exhibit a significant color change as a result of water storage. Sixty seconds
      exposure period does not influence the final color. CLINICAL SIGNIFICANCE:
      Clinicians should be aware of color shifts in flowable resins.

PMID- 24858761
TI  - A comparative evaluation of impact strength of conventionally heat cured and high
      impact heat cured polymethyl methacrylate denture base resins: an in vitro study.
AB  - The denture bases made by using polymethyl methacrylates of Acrylic resin family
      have excellent physical properties, simple to process and easy to reline, rebase
      and repair. One of the inherent disadvantages of this material is the liability
      to break during function. The strength assessment of acrylic resins have been
      made generally by transverse defection tests. AIM: To evaluate the impact
      strength valves of certain brands of commercially available denture base resins
      and suggest their suitability. MATERIALS AND METHODS: The denture bases we made
      using polymethyl methacrylates of acrylic resin family because they have
      excellent physical properties, simple to process and easy to reline and rebase.
      Six commercial brands of polymethyl meth- acrylate, namely Stellon (DPI-India),
      Acralyn-H (Asian Acrylate, India), Trevalon (Dentsply-England), Lucitone 199
      (Dentsply/ York division), Acralyn-H (Super Unbreakable), Trevalon HI (Dentsply,
      Detray division, England) were tested by breaking them using Analog Pendulum
      (ASTM D 256). RESULTS: From the entire study the maximum impact strength was
      reported for Acralyn-H super unbreakable (Asian Acrylates, India) 62.19 joules.
      CONCLUSION: All the analysis led to conclusion that there is basic change in
      material composition within and among the different groups of denture base
      resins. CLINICAL IMPLICATIONS: The complete dentures made using denture base
      resins with high impact strength valves (e.g. Acralyn-H super unbreakable) will
      be more durable and can be used by the patient for considerable period of time,
      i.e. beyond 4 to 5 years.

PMID- 24858762
TI  - Determination of inner implant's volumes: a pilot study for microleakage
      quantification by stereomicroscopy and spectrophotometry.
AB  - AIM: Microleakage quantification of fluids and microorganisms through the
      connections of different implant parts seems to be sparse. Moreover, no data
      exist regarding the determination of the volumes of inner parts of dental implant
      systems. This study aims to determine the volumes of inner parts of three dental
      implant systems with the same interface and to evaluate the microleakage
      phenomenon. MATERIALS AND METHODS: Three implant system sets (Euro-teknika((r)),
      Astra Tech((r)) and Implantium((r))) were used in this study. Implants were
      inoculated with safranin, brain heart infusion and distilled water. After
      inoculation and assembly of the different parts, different inner volumes (V1, V2,
      V3, V4, V5 and V6) were measured and, the surfaces of the micro gaps were
      observed through a stereomicroscope. Implants containing safranin were immersed
      in vials containing distilled water. Samples then were taken to determine optical
      density using a spectrophotometer. RESULTS: Regardless the used substance,
      volumes of the 3-implant systems are different. Although volumes V1, V 2, V 3 and
      V5 appeared to be constant within the same system regardless the used substance,
      volumes V4 and V6 were not. CONCLUSION: The determination of the volumes and the
      evaluation of leaked substance using stereomicroscopic and spectrophotometric
      methods showed the accuracy of these methods and the importance of their use in
      the study of microleakage. CLINICAL SIGNIFICANCE: Leakage is an important factor
      for chronic inflammatory infiltration and marginal bone resorption. Studies have
      shown fluid and bacterial leakage into abutment- implant (A-I) assemblies of
      certain implants with 'closely locked' abutments and the creation of a constant
      bacterial reservoir in the empty space found between the implant and the
      abutment.

PMID- 24858763
TI  - Palatal vault depth influence on the flexural strength of two heat cure acrylic
      denture base resins: an in vitro study.
AB  - Complete dentures often fracture during normal masticatory function. The reason
      could be due to the shape of the palate, i.e. deep, medium or shallow palatal
      vault. This in vitro study was performed to determine the relationship of palatal
      vault depth and flexural strength of two different permanent denture base resins.
      Edentulous maxillary casts of patients were collected from the department of
      prosthodontics, among these the cast with the deepest palatal vault was selected.
      The specimens were then subjected for flexural strength on universal testing
      machine. The results revealed that the denture bases fabricated on medium palatal
      vault depth were best in the flexural strength and denture bases on shallow
      palatal vault depth faired the least. Among the resins the denture bases
      fabricated using high impact heat cure resin, were better than the denture bases
      fabricated using regular heat cure resin. All these results were statistically
      significant except the results between the regular heat cure denture bases and
      high impact heat cure denture bases fabricated on the deep palatal vault depth.
      Also the comparison of fracture energies of denture bases fabricated on deep
      palatal vault with high impact heat cure resin to denture bases fabricated on
      medium and shallow palatal vaults with high impact heat cure resin were not
      significant. It was also observed that all the specimens have fractured in the
      midline. CLINICAL IMPLICATIONS: Palatal vault depth significantly affected the
      flexural strength of heat cure resin. The most frequent mechanical failure of
      heat cure resin is fracture especially at the midline. The denture bases
      fabricated using high impact heat cure resin had best flexural strength than the
      denture bases fabricated using regular heat cure resin which reduced the
      fractures.

PMID- 24858764
TI  - Effects of toothbrush hardness on in vitro wear and roughness of composite
      resins.
AB  - AIM: To investigate and compare the effects of toothbrushes with different
      hardness on abrasion and surface roughness of composite resins. MATERIALS AND
      METHODS: Toothbrushes (DENT. EX Slimhead II 33, Lion Dental Products Co. Ltd.,
      Tokyo, Japan) marked as soft, medium and hard, were used to brush 10 beam-shaped
      specimens of each of three composites resins (Venus [VEN], Venus Diamond [VED]
      and Venus Pearl [VEP]; HeraeusKulzer) with standardized calcium carbonate slurry
      in a multistation testing machine (2N load, 60 Hz). After each of five cycles
      with 10k brushing strokes the wear depth and surface roughness of the specimens
      were determined. After completion of 50k strokes representative samples were
      inspected by SEM. Data were treated with ANOVA and regression analyses (p <
      0.05). RESULTS: Abrasion of the composite resins increased linearly with
      increasing number of brushing cycles (r2 > 0.9). Highest wear was recorded for
      VEN, lowest for VED. Hard brushes produced significantly higher wear on VEN and
      VEP, whereas no difference in wear by toothbrush type was detected for VED.
      Significantly highest surface roughness was found on VED specimens (Ra > 1.5 um),
      the lowest one on VEN (Ra < 0.3 um). VEN specimens showed increased numbers of
      pinhole defects when brushed with hard toothbrushes, surfaces of VEP were
      uniformly abraded without level differences between the prepolymerized fillers
      and the glass filler-loaded matrix, VED showed large glass fillers protruding
      over the main filler-loaded matrix portion under each condition. CONCLUSION:
      Abrasion and surface roughness of composite resins produced by toothbrushing with
      dentifrice depend mainly on the type of restorative resin. Hardness grades of
      toothbrushes have minor effects only on abrasion and surface roughness of
      composite resins. No relationship was found between abrasion and surface
      roughness. CLINICAL SIGNIFICANCE: The grade of the toothbrush used has minor
      effect on wear, texture and roughness of the composite resin.

PMID- 24858765
TI  - Relevance of routine blood pressure assessment among dental patients in Lagos,
      Nigeria.
AB  - AIM: To determine the relevance of routine blood pressure (BP) measurement in
      patients attending the dental clinic. MATERIALS AND METHODS: This was a
      retrospective survey of patients who attended the dental clinic in the Preventive
      Dentistry Department of a tertiary Hospital in Lagos, Nigeria over an eighteen
      month period. Data retrieved from the patient's hospital records included age,
      sex, BP and history of hypertension. Data was analyzed using Epi info 2011
      package. p-value <0.05 was considered statistically significant. RESULTS: A total
      of 1910 patients' records were assessed. Females represented 53.4% (n = 1020) of
      the study population. The mean age was 37.1 +/- 15.0 years (range 18-88 years).
      The prevalence of hypertension was 39.9% (n = 763). Hypertension was stage 1 in
      25.5%, stage 2 in 9.8% and severe in 4.6% of the dental patients. Past medical
      history of hypertension was obtained for 952 patients (49.8%). Of the 763
      patients with high blood pressure, 14.8% had a known history of hypertension,
      while 42.1% were previously undiagnosed (p < 0.0001). Systolic and diastolic BP
      increased with increasing age (p < 0.05) and was significantly higher in males
      than females (p < 0.05). CONCLUSION: The high prevalence of hypertension noted
      among the study population with its potential consequence during dental
      procedures makes the measurement of blood pressure a valuable assessment in a
      dental clinic. CLINICAL SIGNIFICANCE: The high prevalence of hypertension
      particularly the previously undiagnosed cases among the dental patients
      highlights the relevance of routine blood pressure assessment prior to dental
      procedures in contemporary dental practice, so as to minimize the potential
      complications that could occur.

PMID- 24858766
TI  - Prevalence of temporomandibular joint dysfunction and its signs among the
      partially edentulous patients in a village of North Gujarat.
AB  - There is disagreement about the association between missing teeth and the
      presence of temporomandibular disorder (TMD). AIM: To investigate whether, the
      span of edentulousness, gender, number of quadrants involved, pathological
      migration and the type of kennedy's classification are related to the
      temporomandibular joint (TMJ) dysfunction signs. MATERIALS AND METHODS: Clinical
      examination of 250 patients (males 99 and females 151) was done among the age
      group of 35 to 45 years. The patients were partially edentulous for 6 months or
      more and did not wear any kind of prosthesis. RESULTS: Among 250 subjects,
      females showed more TMJ dysfunction signs. Clicking sounds were present in 46.5%,
      mandibular deviation was present in 40% of individuals, TMJ tenderness was
      observed in 32% and masseter was involved in 32% of individual. Temporomandibular
      joint dysfunction signs in relation to pathologic migration of teeth show that
      clicking and mandibular deviation was present in 54.5 and 49.2% and among muscles
      masseter muscle tenderness 41.9% was more commonly present. Masseter muscle
      tenderness 64.1% was seen in individuals who were edentulous for more than 5
      years. CONCLUSION: Females subjects had a significantly higher prevalence of TMJ
      dysfunction signs then male subjects. As the span and time of edentulousness, the
      number of missing teeth and the number of quadrant involved increased, the signs
      of dysfunction became more prevalent. Among the TMJ dysfunction signs deviation
      and clicking sound were most frequently observed. The masseter muscle was most
      commonly affected and demonstrated muscle tenderness.

PMID- 24858767
TI  - New regression equations for mixed dentition space analysis in an Iranian
      population.
AB  - AIMS: Prediction of the mesiodistal crown width of unerupted canines and
      premolars is an important aspect of mixed dentition analysis. The accuracy of
      Tanaka-Johnston equations, the most commonly method, is questionable when it is
      applied to different ethnic groups. In this study, we aimed to develop a new
      regression equation for this prediction in an Iranian population. MATERIALS AND
      METHODS: The dental casts of 120 Iranian subjects with complete permanent
      dentition were selected. Mesiodistal crown widths of teeth were measured with
      digital caliper. In the first part of the study, the correlation and linear
      regression equations between four mandibular incisors and the canine-premolars
      segments of both arches were developed (modified Tanaka-Johnston equation). In
      the second part, as a new method, correlation and linear regression equations
      were developed between the sum of mandibular central incisors-maxillary first
      molars and the canine-premolars segments. RESULTS: It was found that the
      correlation coefficients between the sum of mandibular central incisors-maxillary
      first molars and the maxillary and mandibular canine-premolars segments were
      higher (r = 0.66, 0.68 respectively) than the one between the four mandibular
      incisors and the canine-premolars segments (r = 0.58. 0.64). CONCLUSION: New
      linear regression equations were derived. In this study, the sum of mandibular
      central incisors and maxillary first molars was better predictor for unerupted
      canines and premolars. This novel approach allows the prediction of width of
      unerupted canines and premolars to take place at earlier age. CLINICAL
      SIGNIFICANCE: Using the new method, orthodontists could take advantage of mixed
      dentition analysis at earlier age. Moreover, to test the derived equations on a
      larger sample size and in other ethnicities is highly recommended.

PMID- 24858768
TI  - Denture hygiene habits among elderly patients wearing complete dentures.
AB  - OBJECTIVE: To determine the denture hygiene habits in complete denture patients
      according to their age and time of dentures. METHODS: In this study a self
      administered structured was developed to know the attitude of the patients
      regarding denture hygiene in the department of Prosthodontics. The total study
      sample consisted of 230 subjects including 124 (53.9%) males and 106 (46.1%)
      females. Data was analyzed using SPSS version 15.0 with chi-square test at p
      value <0.05. RESULTS: Nearly half of the subjects clean their dentures daily
      once. Participants from the younger age group and who had been wearing dentures
      since 2 years maintain better frequency of cleaning. The majority of these
      subjects used water and brush for denture cleansing. After seeing the condition,
      half of the dentures were rated as good 50.3%, followed by fair and poor as 29.5
      and 20.2% respectively. CLINICAL SIGNIFICANCE: Poor condition of complete
      dentures seen in the population is mainly due to irregularly cleansing habits and
      also less usage of cleansing solutions. Dentists should give proper instructions
      regarding maintenance of denture hygiene.

PMID- 24858769
TI  - Evaluation of gingival inflammation in patients using ovulation induction drugs
      before and after scaling.
AB  - OBJECTIVES: To determine and correlate the effect of clomiphene citrate,
      Letrozole in women undergoing infertility treatment on the gingival inflammatory
      status. MATERIALS AND METHODS: The present study is a randomized controlled
      clinical trial which consisted of 26 women using CC for three menstrual cycles,
      26 women using CC for more than three cycles, 26 women using Letrozole. All
      subjects were clinically examined for plaque levels (Plaque Index), gingival
      inflammation, bleeding on probing (Gingival Index, Sulcus Bleeding Index).
      Scaling was done to all patients and all periodontal parameters were reassessed 1
      month after scaling. The results were compared with a control group of 26 women
      matched for age, educational status and professional level, and oral habits and
      who had never used ovulation drugs. RESULTS: Baseline scores of all the test
      groups showed higher amount of plaque levels and inflammation compared to
      control. (p < 0.05). After scaling a significant reduction in inflammation was
      observed in all the test groups along with the control group (p < 0.0001), but
      women using the drugs showed persistence of inflammation compared to control (p <
      0.01). CONCLUSION: It can be concluded from the present study that the presence
      of elevated levels of hormones due to the effect of ovulation induction drugs may
      be the reason for the gingival inflammation in test groups.

PMID- 24858770
TI  - Dental prosthetic status and prosthetic needs of the institutionalized elderly
      living in geriatric homes in Hyderabad: a pilot study.
AB  - INTRODUCTION: To promote oral health among the elderly, we need to know their
      prosthetic status and prosthetic need. Hence, a survey of prosthetic status and
      need of elderly inmates of geriatric homes in Hyderabad was done. MATERIALS AND
      METHODS: A cross-sectional study was undertaken, and 174 subjects aged 60 years
      and above were examined of which 103 were male and 71 were female (59.2% males
      and 40.8% females). The oral examination of the study subjects was carried out
      using basic oral health surveys, WHO 1997 criteria. RESULTS: Majority of the
      subjects, 73 (70.8%) males and 53 (74.6%) females had no prosthesis. Only 4.6%
      had complete dentures and 21.1% had removable partial dentures and 10.9% had
      single/multiple bridges. Need for any prosthesis was (83.5%) male and 63 (88.7%)
      female subjects and nearly 82. 8% subjects required one-unit prosthesis.
      CONCLUSION: Dental prosthetic status of people living in geriatric homes is very
      poor and there is high unmet need for prosthetic care existed among the
      institutionalized elderly surveyed.

PMID- 24858771
TI  - The relationship between prosthetic status and the Geriatric Oral Health
      Assessment Index in a group of institutionalized elderly of an Indian city: a
      cross-sectional study.
AB  - AIM: To assess and compare the quality of life and oral health status among
      institutionalized elderly in Pune. MATERIALS AND METHODS: A cross-sectional,
      quantitative exploratory study was conducted in persons 60 years of age in an
      institutionalized elderly home. The GOHAI questionnaire was completed by a single
      examiner, who interviewed the patients in their local language. The oral
      examination was carried out according to WHO oral health survey using the DMFT
      index, community periodontal index (CPI), periodontal loss of attachment (PLA),
      prosthetic use, and needs according to criteria established by the WHO by a
      calibrated examiner. Descriptive analysis was carried out using absolute and
      relative frequencies of the qualitative variables and means with respective
      standard deviations for the quantitative variables. The Student's t-test was
      applied to compare groups. RESULTS: Out of the total 110 individuals interviewed
      for the study, 64% were males and 36% were females. Individuals with up to 20
      missing teeth and individuals with more than 20 missing teeth were 20 and 80%
      respectively. Based on the prosthetic need, 66% individuals needed replacement of
      teeth by dentures in one or both arches while 34% did not need any replacement by
      complete denture. The mean value for physical dimension was 5.40 whereas for
      psychosocial dimension, pain/discomfort and behavioral dimension were 8.02, 4.58
      and 7.32. CONCLUSION: The quality of life was found to be more favorable in
      individuals with less than 20 teeth missing. The quality of life among complete
      denture wearers in both the arches was better as compared to the quality of life
      among nondenture wearers. Prosthetic replacement by complete denture helps the
      individuals to maintain better oral health. CLINICAL SIGNIFICANCE: The data
      obtained from the present study may serve as a reference point for comparisons of
      the magnitude of quality-of-life indicators relating to oral health.

PMID- 24858772
TI  - Calcifying odontogenic cyst: a rare report of a nonneoplastic variant associated
      with cholesterol granuloma.
AB  - AIM: To report a case of a non-neoplastic variant of calcifying odontogenic cyst
      (COC) with the lining epithelium showing ameloblastomatous proliferation and
      capsule exhibiting features of a cholesterol granuloma. The importance of
      delineating this histologic variant from unicystic ameloblastoma and the
      formation of cholesterol granuloma in this variant is discussed. BACKGROUND:
      Calcifying odontogenic cyst is a developmental jaw cyst, which presents itself as
      both the neoplastic and the non-neoplastic forms. The ameloblastomatous variant
      of COC is often mistaken for unicystic ameloblastoma and treated aggressively.
      CASE REPORT: A 68-year-old female who presented with a cystic enlargement of the
      posterior mandible on the right side was suggestive of unicystic ameloblastoma
      based on radiography and initial biopsy report. Microscopic examination of the
      excision specimen, however, was fitting in favor of calcifying odontogenic cyst
      with ameloblastomatous proliferation. CONCLUSION: Identifying the non-neoplastic
      ameloblastomatous variant of COC from a cystic ameloblastoma is crucial as the
      treatment of the two lesions vary considerably. CLINICAL SIGNIFICANCE: This case
      emphasizes the need for thorough examination of the entire surgical specimen
      before arriving at an appropriate diagnosis.

PMID- 24858773
TI  - Nonsurgical management of large periapical lesion in mature and immature teeth
      using different calcium hydroxide formulations: case series.
AB  - This case series evaluates the effectiveness of different calcium hydroxide
      formulations with various vehicles in management of large periapical lesion in
      mature and immature teeth. This will help clinicians to make informed judgments
      about which formulations of calcium hydroxide should be used for specific
      endodontic procedures.

PMID- 24858774
TI  - Primary mucosal melanoma: report of two cases.
AB  - Primary mucosal malignant melanoma is of unusual occurrence and poor prognosis.
      We report two cases of primary mucosal melanoma, one in a 70-year-old male in the
      palate and the other in a 73-year-old female in the maxillary sinus. Early
      diagnosis and proper clinical and cytologic evaluation is necessary to institute
      therapeutic intervention. These cases are reported on account of their rarity of
      occurrence and difficulty of treatment.

PMID- 24858776
TI  - Can the use of antibiotics interfere with the success of dental osseointegrated
      implants in diabetic patients?
AB  - AIM: The present review aims to discuss the last 10 years published data on the
      topic of the use of osseointegrated implants in diabetic subjects, particularly
      regarding the influence of antibiotics administration in the perioperative
      period. BACKGROUND: In the last decades, oral rehabilitation significantly has
      evolved particularly with the use of osseointegrated implants. Increased life
      expectation of population is reflecting in a greater number of diabetic patients
      who might require dental osseointegrated implants rehabilitation. Diabetes was
      considered for a long time as a contraindication for oral implant placement. In
      this context, the use of antibiotics is still a controversial factor when we
      correlate it to implant success rate. REVIEW RESULTS: Although 228 articles were
      initially selected for evaluation of proposed criteria, only 16 articles were
      considered valid. Among the 16 selected articles, only six articles represented
      clinical research that discussed the influence of the antibiotic in the success
      of osseointegration of dental implants in diabetic subjects. Five were
      retrospective studies and one a prospective research. CONCLUSION: Data favors the
      use of antibiotics without significant side effects but clinical investigations
      of the need of prophylaxis antibiotic or therapeutic antibiotics are still
      scarce. The lack of adequate methodology is one of the main problems of the
      current articles. It is important to emphasize that studies should present
      detailed methodology in order to allow reproducibility. CLINICAL SIGNIFICANCE:
      Permanent tooth loss is a pathological condition that affects millions of people
      worldwide. The possibility of successful treatment of edentulous areas through
      osseointegrated implants in those systemic compromised patients is a matter of
      scientific discussion. Although antimicrobial agents must be used rationally and
      carefully to avoid development of bacterial resistance, more studies are needed
      in order to support evidence regarding the influence of antibiotics in the
      success of dental implant surgery in diabetic patients.

PMID- 24858775
TI  - C-arm fluoroscopy: a reliable modality for retrieval of foreign bodies in the
      maxillofacial region.
AB  - The anatomic complexity of the maxillofacial region makes the retrieval of
      foreign bodies a daunting task for the maxillofacial Surgeon. Moreover the
      inability of 2-dimensional imaging to precisely locate foreign bodies makes it
      challenging. The anatomic proximity of critical structures and esthetic
      considerations limits the access and thus poses a greater challenge for the
      surgeon in cases of foreign body retrieval. Hereby we propose a simple technique
      and a case report to support, the retrieval of small (<5 mm greatest dimension)
      objects from the maxillofacial region. The present technique uses a 2 dimensional
      mobile C arm Fluoroscopy and a needle triangulation method to precisely locate a
      loosened miniplate screw in the mandibular angle region.

PMID- 24858777
TI  - Microbial flora in oral diseases.
AB  - The oral cavity being the hub of gamut of microbes, promotes the establishment of
      distinct microbial communities, such as on the mucosa and teeth. Metabolism of
      these organisms facilitates the attachment and growth of the subsequent
      colonisers. A delicate balance is maintained in the microbial ecosystem, with
      these organisms contributing to normal development and defences. However, any
      change or disruption in the microbial profile due to either intrinsic or
      extrinsic factors can result in an unfavorable shift toward pathogenic organisms
      triggering various diseases like dental caries or periodontitis. Furthermore,
      recent findings also state that these microorganisms may lead to systemic
      diseases like diabetes or atherosclerosis. This article is an attempt to give an
      overview of the altered flora in diseased states.

PMID- 24858778
TI  - Emergent areas to visualize by the journal strategy holders.

PMID- 24858779
TI  - A longitudinal study on risk factors for neck and shoulder pain among young
      adults in the transition from technical school to working life.
AB  - OBJECTIVES: The study examined the course of neck and shoulder pain among a
      cohort of technical school students entering working life. We also aimed to
      identify work-related and individual risk factors for neck and shoulder pain
      during this transition period. METHODS: The study was designed as a prospective
      cohort study following 420 technical school students (167 student hairdressers,
      118 student electricians, and 135 media/design students) from school, through
      their apprenticeship and into working life. Every 4 (th)month over a 6.5 year
      period (2002-2009), the participant's neck and shoulder pain for the preceding
      four weeks was assessed. Mechanical and psychosocial workplace factors as well as
      individual factors were evaluated at baseline and/or during the follow-up period.
      Data were analyzed by generalized estimating equations (GEE). RESULTS: We found a
      significant increase in neck and shoulder pain over time in the transition from
      technical school to working life. High mechanical workload was associated with
      neck and shoulder pain among women, while a high level of shoulder muscle
      endurance capacity was associated with lower rates of neck and shoulder pain
      among men. Perceived muscle tension and ethnicity were the most consistent
      predictors for neck and shoulder pain, found among both women and men.
      CONCLUSION: Increased neck and shoulder pain was found in the transition from
      technical school to working life, and both work-related and individual factors
      were associated with pain development.

PMID- 24858780
TI  - River organic matter shapes microbial communities in the sediment of the Rhone
      prodelta.
AB  - Microbial-driven organic matter (OM) degradation is a cornerstone of benthic
      community functioning, but little is known about the relation between OM and
      community composition. Here we use Rhone prodelta sediments to test the
      hypothesis that OM quality and source are fundamental structuring factors for
      bacterial communities in benthic environments. Sampling was performed on four
      occasions corresponding to contrasting river-flow regimes, and bacterial
      communities from seven different depths were analyzed by pyrosequencing of 16S
      rRNA gene amplicons. The sediment matrix was characterized using over 20
      environmental variables including bulk parameters (for example, total nitrogen,
      carbon, OM, porosity and particle size), as well as parameters describing the OM
      quality and source (for example, pigments, total lipids and amino acids and
      delta(13)C), and molecular-level biomarkers like fatty acids. Our results show
      that the variance of the microbial community was best explained by delta(13)C
      values, indicative of the OM source, and the proportion of saturated or
      polyunsaturated fatty acids, describing OM lability. These parameters were traced
      back to seasonal differences in the river flow, delivering OM of different
      quality and origin, and were directly associated with several frequent bacterial
      operational taxonomic units. However, the contextual parameters, which explained
      at most 17% of the variance, were not always the key for understanding the
      community assembly. Co-occurrence and phylogenetic diversity analysis indicated
      that bacteria-bacteria interactions were also significant. In conclusion, the
      drivers structuring the microbial community changed with time but remain closely
      linked with the river OM input. 

PMID- 24858781
TI  - Phage and bacteria support mutual diversity in a narrowing staircase of
      coexistence.
AB  - The competitive exclusion principle states that phage diversity M should not
      exceed bacterial diversity N. By analyzing the steady-state solutions of
      multistrain equations, we find a new constraint: the diversity N of bacteria
      living on the same resources is constrained to be M or M+1 in terms of the
      diversity of their phage predators. We quantify how the parameter space of
      coexistence exponentially decreases with diversity. For diversity to grow, an
      open or evolving ecosystem needs to climb a narrowing 'diversity staircase' by
      alternatingly adding new bacteria and phages. The unfolding coevolutionary arms
      race will typically favor high growth rate, but a phage that infects two
      bacterial strains differently can occasionally eliminate the fastest growing
      bacteria. This context-dependent fitness allows abrupt resetting of the 'Red
      Queen's race' and constrains the local diversity. 

PMID- 24858782
TI  - Amphibian skin may select for rare environmental microbes.
AB  - Host-microbe symbioses rely on the successful transmission or acquisition of
      symbionts in each new generation. Amphibians host a diverse cutaneous microbiota,
      and many of these symbionts appear to be mutualistic and may limit infection by
      the chytrid fungus, Batrachochytrium dendrobatidis, which has caused global
      amphibian population declines and extinctions in recent decades. Using bar-coded
      454 pyrosequencing of the 16S rRNA gene, we addressed the question of symbiont
      transmission by examining variation in amphibian skin microbiota across species
      and sites and in direct relation to environmental microbes. Although acquisition
      of environmental microbes occurs in some host-symbiont systems, this has not been
      extensively examined in free-living vertebrate-microbe symbioses. Juvenile
      bullfrogs (Rana catesbeiana), adult red-spotted newts (Notophthalmus
      viridescens), pond water and pond substrate were sampled at a single pond to
      examine host-specificity and potential environmental transmission of microbiota.
      To assess population level variation in skin microbiota, adult newts from two
      additional sites were also sampled. Cohabiting bullfrogs and newts had distinct
      microbial communities, as did newts across the three sites. The microbial
      communities of amphibians and the environment were distinct; there was very
      little overlap in the amphibians' core microbes and the most abundant
      environmental microbes, and the relative abundances of OTUs that were shared by
      amphibians and the environment were inversely related. These results suggest
      that, in a host species-specific manner, amphibian skin may select for microbes
      that are generally in low abundance in the environment. 

PMID- 24858783
TI  - Nutrients drive transcriptional changes that maintain metabolic homeostasis but
      alter genome architecture in Microcystis.
AB  - The cyanobacterium Microcystis aeruginosa is a globally distributed bloom-forming
      organism that degrades freshwater systems around the world. Factors that drive
      its dispersion, diversification and success remain, however, poorly understood.
      To develop insight into cellular-level responses to nutrient drivers of
      eutrophication, RNA sequencing was coupled to a comprehensive metabolomics survey
      of M. aeruginosa sp. NIES 843 grown in various nutrient-reduced conditions.
      Transcriptomes were generated for cultures grown in nutrient-replete (with
      nitrate as the nitrogen (N) source), nitrogen-reduced (with nitrate, urea or
      ammonium acting as the N sources) and phosphate-reduced conditions. Extensive
      expression differences (up to 696 genes for urea-grown cells) relative to the
      control treatment were observed, demonstrating that the chemical variant of
      nitrogen available to cells affected transcriptional activity. Of particular
      note, a high number of transposase genes (up to 81) were significantly and
      reproducibly up-regulated relative to the control when grown on urea. Conversely,
      phosphorus (P) reduction resulted in a significant cessation in transcription of
      transposase genes, indicating that variation in nutrient chemistry may influence
      transcription of transposases and may impact the highly mosaic genomic
      architecture of M. aeruginosa. Corresponding metabolomes showed comparably few
      differences between treatments, suggesting broad changes to gene transcription
      are required to maintain metabolic homeostasis under nutrient reduction. The
      combined observations provide novel and extensive insight into the complex
      cellular interactions that take place in this important bloom-forming organism
      during variable nutrient conditions and highlight a potential unknown molecular
      mechanism that may drive Microcystis blooms and evolution. 

PMID- 24858785
TI  - Bone quality in older adults with intellectual disabilities.
AB  - Although osteoporosis is a progressive bone disease leading to increased risk of
      fracture, it has rarely been investigated on a large scale in older people with
      intellectual disabilities (ID). In this study, 768 persons with ID (aged >= 50
      years) were measured with quantitative ultrasound to determine the prevalence of
      low bone quality. The association of low bone quality with patient
      characteristics, mobility, physical activity, body mass index (BMI), prior
      fractures, anticonvulsant drug use, intake of calcium, and vitamin D3 levels was
      also investigated. The prevalence of low bone quality was 43.9%. Low bone quality
      was positively associated with female gender, age, more severe level of ID,
      mobility impairment, and anticonvulsant drug use, and negatively with BMI. In
      clinical practice, people with ID who are at risk for low bone quality should
      periodically be screened for osteoporosis and be given advice about nutritional
      supplements and appropriate lifestyle.

PMID- 24858784
TI  - Interactions between Thaumarchaea, Nitrospira and methanotrophs modulate
      autotrophic nitrification in volcanic grassland soil.
AB  - Ammonium/ammonia is the sole energy substrate of ammonia oxidizers, and is also
      an essential nitrogen source for other microorganisms. Ammonia oxidizers
      therefore must compete with other soil microorganisms such as methane-oxidizing
      bacteria (MOB) in terrestrial ecosystems when ammonium concentrations are
      limiting. Here we report on the interactions between nitrifying communities
      dominated by ammonia-oxidizing archaea (AOA) and Nitrospira-like nitrite
      oxidizing bacteria (NOB), and communities of MOB in controlled microcosm
      experiments with two levels of ammonium and methane availability. We observed
      strong stimulatory effects of elevated ammonium concentration on the processes of
      nitrification and methane oxidation as well as on the abundances of
      autotrophically growing nitrifiers. However, the key players in nitrification and
      methane oxidation, identified by stable-isotope labeling using (13)CO2 and
      (13)CH4, were the same under both ammonium levels, namely type 1.1a AOA,
      sublineage I and II Nitrospira-like NOB and Methylomicrobium-/Methylosarcina-like
      MOB, respectively. Ammonia-oxidizing bacteria were nearly absent, and ammonia
      oxidation could almost exclusively be attributed to AOA. Interestingly, although
      AOA functional gene abundance increased 10-fold during incubation, there was very
      limited evidence of autotrophic growth, suggesting a partly mixotrophic
      lifestyle. Furthermore, autotrophic growth of AOA and NOB was inhibited by active
      MOB at both ammonium levels. Our results suggest the existence of a previously
      overlooked competition for nitrogen between nitrifiers and methane oxidizers in
      soil, thus linking two of the most important biogeochemical cycles in nature.

PMID- 24858786
TI  - Primary caregivers' awareness and perception of early-onset dementia conditions
      in adolescents and young and middle-aged adults with Down syndrome.
AB  - The present study aims to investigate the onset of dementia conditions using the
      Dementia Screening Questionnaire for Individuals with Intellectual Disabilities
      (DSQIID) scale and to identify the possible factors associated with DSQIID scores
      in people with Down syndrome (DS). The study population was recruited from the
      voluntary registry members of the Republic of China Foundation for Persons with
      Down syndrome; primary caregivers provided DSQIID information on 196 adolescents
      and adults with DS (aged 15-48 years) who were entered into the database and
      analyzed using SPSS 20.0 software. The results described the distribution of
      early-onset dementia conditions in 53 adolescents and adults with DS, and 2.6% of
      the subjects with DS had possible dementia (DSQIID score ? 20). Univariate
      analyses found that older age (p=0.001) and comorbid conditions (p=0.003) were
      significantly associated with DSQIID scores. Older subjects were more likely to
      have higher DSQIID scores than were younger age groups after ANOVA and Scheffe's
      tests. Lastly, a multiple linear regression analysis revealed that age (p<0.01),
      severe disability level (p<0.05) and comorbid condition (p<0.01) significantly
      explained 13% of the variation in DSQIID scores after adjusting for the factors
      of gender, education level and multiple disabilities in adolescents and adults
      with DS. The study highlights that future research should focus on the occurrence
      of dementia in people with DS and on identifying its influencing factors based on
      sound measurements, to initiate appropriate healthy aging policies for this group
      of people.

PMID- 24858787
TI  - Factors influencing the motor development of prematurely born school-aged
      children in Brazil.
AB  - Despite technological advances in neonatology, premature children are still
      susceptible to disruptions in neurological development. The current study aimed
      to analyze the factors that influence motor development in prematurely born
      school-aged children in Brazil. This cross-sectional study involved 100
      "apparently normal" children, aged 8-10 years, born at less than 35 weeks of
      gestation or with birth weight< 1500 g. Their motor development was assessed
      using the Movement Assessment Battery for Children (MABC-2). The children's
      neuropsychological and academic performance was assessed with the Token Test (TT)
      and Teste de Desempenho Escolar (TDE), respectively. Parents answered questions
      regarding the child's clinical history and behavior using the Strengths and
      Difficulties Questionnaire (SDQ) and family environment resources (RAF).
      Hierarchical multivariate analyses revealed that 39% of the children scored lower
      on the MABC-2, as compared to that expected for their age (manual dexterity: 49%;
      balance: 35%; throwing/catching a ball: 26%). Multivariate analysis indicated
      that the lower the birth weight, the maternal age at childbirth, and the RAF
      score, the greater was the chance of impairment on the MABC-2 scores. The
      probability of having an impairment MABC-2 scores was four times higher when the
      mother was not employed. We also found associations between MABC-2 scores and the
      tasks of tying shoes and opening/closing zippers and buttons. Factors related to
      children's home environments and birth weight are associated with deficient motor
      performance in prematurely born Brazilian school-aged children. Deficient motor
      skills were also associated with difficulty in performing functional tasks
      requiring greater manual dexterity.

PMID- 24858788
TI  - Engineered, highly productive biosynthesis of artificial, lactonized statin side
      chain building blocks: The hidden potential of Escherichia coli unleashed.
AB  - We have recently reported the development of an efficient, whole-cell process for
      chemoenzymatic production of key chiral intermediates in statin synthesis by
      employing high-density Escherichia coli culture with the overexpressed
      deoxyribose-5-phosphate aldolase (DERA). The optically pure, 6-substituted cyclic
      hemiacetals can be used for the synthesis of atorvastatin, rosuvastatin and
      pitavastatin using further chemical steps. All of the synthetic routes
      established to date begin with a regiospecific oxidation of these lactol
      intermediates into the corresponding lactones, followed by several steps yielding
      6-substituted, open-chain or lactonized derivatives which can be coupled by
      various approaches with the heterocyclic part of the statin molecule. Here we
      report for the first time the use of PQQ-dependent glucose dehydrogenases for a
      highly efficient, regioselective oxidation of artificial, derivatized
      aldohexoses, more specifically, the statin lactol intermediates. First, PQQ
      dependent dehydrogenases of both soluble and membrane-bound type were
      characterized for their activity toward various DERA-derived lactols. Further, we
      describe a highly productive whole-cell system for oxidation of these 2,4
      dideoxyaldopyranoses using a PQQ-dependent glucose dehydrogenase (Gcd)
      overexpressed in E. coli while taking advantage of the respiratory chain as the
      mediator of the electron transfer to oxygen. Finally, a two-step artificial
      biosynthetic pathway was developed by unleashing the intrinsic genetic potential
      of E. coli. The combined overexpression of the endogenous DERA and the membrane
      bound, PQQ-dependent glucose dehydrogenase, the latter being coupled to the
      respiratory chain, allows direct biosynthesis of 6-substituted lactones in a
      highly productive, high-yield, cost-effective and industrially scalable process. 

PMID- 24858789
TI  - Two-stage transcriptional reprogramming in Saccharomyces cerevisiae for
      optimizing ethanol production from xylose.
AB  - Conversion of lignocellulosic material to ethanol is a major challenge in second
      generation bio-fuel production by yeast Saccharomyces cerevisiae. This report
      describes a novel strategy named "two-stage transcriptional reprogramming (TSTR)"
      in which key gene expression at both glucose and xylose fermentation phases is
      optimized in engineered S. cerevisiae. Through a combined genome-wide screening
      of stage-specific promoters and the balancing of the metabolic flux, ethanol
      yields and productivity from mixed sugars were significantly improved. In a
      medium containing 50g/L glucose and 50g/L xylose, the top-performing strain WXY12
      rapidly consumed glucose within 12h and within 84h it consistently achieved an
      ethanol yield of 0.48g/g total sugar, which was 94% of the theoretical yield.
      WXY12 utilizes a KGD1 inducible promoter to drive xylose metabolism, resulting in
      much higher ethanol yield than a reference strain using a strong constitutive
      PGK1 promoter. These promising results validate the TSTR strategy by
      synthetically regulating the xylose assimilation pathway towards efficient xylose
      fermentation. 

PMID- 24858790
TI  - Open aortic repair up to previous abdominal aortic surgery.
AB  - BACKGROUND: To determine whether direct open repair of thoracoabdominal aortic
      aneurysms after previous abdominal aortic surgery is a safe option. METHODS: Ten
      patients were operated between January 2006 and January 2012. Mean age was 70
      years (62-78 years). Four aneurysms (Crawford type III) were treated by firstly
      performed bypasses from the upper thoracic aorta to the celiac trunk, the
      superior mesenteric artery, and the left renal artery. Secondly performed aortic
      repair included revascularization of intercostal arteries identified as critical
      for spinal cord and the right renal artery. Similarly, the 6 aneurysms (Crawford
      type IV) were treated by firstly performed bypass from the upper thoracic aorta
      to the left renal artery before aortic repair. RESULTS: The overall mortality and
      paraplegia rates were nil. The maximal creatinin sera variation was 48 +/- 16%
      with return to the baseline level before discharge. Five patients presented with
      pulmonary complications. The duration of stay was 9.3 days (2-29) in the
      intensive care unit and 24 days (10-40) in the surgical unit. The mean follow-up
      was 35 months. No patient died during the follow-up. CONCLUSIONS: In our
      experience, open redo aortic surgery appears to be safe. The main relevant point
      is the sequential reconstruction of the aorta including bypasses of the visceral
      branches that lowered the visceral ischemic damage because of high level aortic
      cross-clamping.

PMID- 24858791
TI  - Electrophysiological, hemodynamic, and metabolic response to open procedure or
      endovascular repair of infrarenal aortic aneurysms.
AB  - BACKGROUND: The occurrence of cardiovascular diseases in the group of patients
      undergoing vascular surgery because of abdominal aorta aneurysm is very high.
      Endovascular procedures are regarded as hemodynamically safer for the patients.
      The aim of this study was to compare the changes in electrophysiological,
      hemodynamic, and metabolic parameters depending on the type of operation, using
      invasive hemodynamic monitoring and Holter electrocardiography recording.
      METHODS: A prospective, observational, nonrandomized study was conducted to
      compare dynamic changes of electrophysiological parameters (dominant rhythm,
      arrhythmia, corrected QT interval (QTc), invasive blood pressure, electrolytes,
      and acid-base balance in defined points during perioperative time in 2 groups:
      vascular prosthesis implantation group (91 patients) and stent-graft implantation
      group (83 patients). RESULTS: The study group comprised 174 consecutive adult
      Caucasian patients (mean age 64.4 +/- 8.9 years in stent-graft group and 70.0 +/-
      7.5 years in vascular prosthesis implantation group). Although patients in the
      stent-graft implantation group were younger, they were diagnosed with lower limbs
      vascular atherosclerosis, type 2 diabetes mellitus, and a lower left ventricle
      ejection fraction more often than patients in the open procedure group. During
      the open procedure, higher blood pressure amplitudes (P = 0.00009), higher
      decrease in pH (P = 0.049), increase in the arterial lactate level (P = 0.00002),
      prolonged QTc values (P = 0.001), more frequent ventricular extrasystoles (P =
      0.005), and cardiovascular deaths were observed, when compared with those
      observed during the endovascular aneurysm repair. CONCLUSIONS: When compared with
      the chosen techniques, the one for infrarenal abdominal aneurysm was found to be
      associated with significant differences in electrophysiological, hemodynamic, and
      metabolic parameters.

PMID- 24858792
TI  - Does Attending Worship Mitigate Racial/Ethnic Discrimination in Influencing
      Health Behaviors? Results From an Analysis of the California Health Interview
      Survey.
AB  - Existing research suggests that religious institutions play a significant role in
      improving the health of communities, particularly those coping with racial and
      ethnic discrimination. Using the California Health Interview Survey, this article
      examines the relationship of self-reported experiences of racial/ethnic
      discrimination, worship attendance, and several health behaviors. Supporting
      existing research, higher self-reported racial/ethnic discrimination is
      associated with worse health behaviors. Logistic regression models indicate that
      the odds of engaging in healthy lifestyle behaviors significantly increase for
      those who report attending worship, compared with those who do not attend
      worship, with variations by race/ethnicity. Worship attendance moderates the
      association between discrimination and binge drinking, but does not moderate the
      association for smoking, walking, or being obese. Findings suggest that religious
      attendance plays an important role in the health and well-being of all population
      groups. More research is needed to ascertain the reasons why attending worship
      may have the ability to mitigate the relationship between racial/ethnic
      discrimination and health.

PMID- 24858793
TI  - Cognitive procedural learning among children and adolescents with or without
      spastic cerebral palsy: the differential effect of age.
AB  - INTRODUCTION: Children learn to engage their surroundings skillfully, adopting
      implicit knowledge of complex regularities and associations. Probabilistic
      classification learning (PCL) is a type of cognitive procedural learning in which
      different cues are probabilistically associated with specific outcomes. Little is
      known about the effects of developmental disorders on cognitive skill
      acquisition. METHODS: Twenty-four children and adolescents with cerebral palsy
      (CP) were compared to 24 typically developing (TD) youth in their ability to
      learn probabilistic associations. Performance was examined in relation to general
      cognitive abilities, level of motor impairment and age. RESULTS: Improvement in
      PCL was observed for all participants, with no relation to IQ. An age effect was
      found only among TD children. CONCLUSIONS: Learning curves of children with CP on
      a cognitive procedural learning task differ from those of TD peers and do not
      appear to be age sensitive.

PMID- 24858794
TI  - Impaired visually guided weight-shifting ability in children with cerebral palsy.
AB  - The ability to control voluntary weight shifting is crucial in many functional
      tasks. To our knowledge, weight shifting ability in response to a visual stimulus
      has never been evaluated in children with cerebral palsy (CP). The aim of the
      study was (1) to propose a new method to assess visually guided medio-lateral
      (M/L) weight shifting ability and (2) to compare weight-shifting ability in
      children with CP and typically developing (TD) children. Ten children with
      spastic diplegic CP (Gross Motor Function Classification System level I and II;
      age 7-12 years) and 10 TD age-matched children were tested. Participants played
      with the skiing game on the Wii Fit game console. Center of pressure (COP)
      displacements, trunk and lower-limb movements were recorded during the last
      virtual slalom. Maximal isometric lower limb strength and postural control during
      quiet standing were also assessed. Lower-limb muscle strength was reduced in
      children with CP compared to TD children and postural control during quiet
      standing was impaired in children with CP. As expected, the skiing game mainly
      resulted in M/L COP displacements. Children with CP showed lower M/L COP range
      and velocity as compared to TD children but larger trunk movements. Trunk and
      lower extremity movements were less in phase in children with CP compared to TD
      children. Commercially available active video games can be used to assess
      visually guided weight shifting ability. Children with spastic diplegic CP showed
      impaired visually guided weight shifting which can be explained by non-optimal
      coordination of postural movement and reduced muscular strength. 

PMID- 24858795
TI  - Trait emotional suppression is associated with increased activation of the
      rostral anterior cingulate cortex in response to masked angry faces.
AB  - Emotional suppression (ES) is a critical component of the ability to self
      regulate emotion. However, people who chronically use ES as a primary strategy
      often experience heightened anxiety or depression. Although functional
      neuroimaging studies have extensively mapped the brain regions involving in
      emotional regulation, the neural substrates of ES as a trait construct remain
      relatively unexplored. Using a validated backward masked facial affect paradigm,
      we examined the association between ES and functional brain responses to masked
      angry, fearful, and happy faces. Healthy adults underwent functional MRI and
      completed the Courtauld Emotional Control Scale as a measure of ES. Correlations
      between self-reported ES and brain responses to the facial affect stimuli
      (affective>neutral) were evaluated within the brain regions involved in emotional
      processing, including the amygdala, insula, anterior cingulate cortex, medial
      prefrontal cortex, and orbitofrontal cortex. In response to angry faces, higher
      trait tendency to suppress anger and anxiety was significantly correlated with
      increased activation within the rostral anterior cingulate cortex, whereas no
      correlation was observed for masked happy or fearful faces. This finding suggests
      that the rostral anterior cingulate cortex contributes to the unconscious
      suppression of emotional responses to angry facial affect and may play a role in
      the mediating anatomy of trait ES. 

PMID- 24858796
TI  - Lags in measuring eye-hand coordination.
AB  - We challenge a number of the claims for novelty and innovation made in a recent
      published paper (Lee et al., 2014) with regard to a computerised methodology that
      these authors present for assessing eye-hand coordination (EHC). Published work
      on similar pre-existing computerised systems is discussed and arguments made for
      these alternative systems being equal, if not superior, in terms of their
      innovativeness. The commentary does not dispute the usefulness of systems such as
      the one described by Lee et al. Rather, in the interests of scholarship it
      provides an accompanying insight into the significant scholarly contributions
      previously, and contemporaneously, being made by other research groups working in
      this area. 

PMID- 24858797
TI  - An in vitro blood-brain barrier model combining shear stress and endothelial
      cell/astrocyte co-culture.
AB  - BACKGROUND: In vitro blood-brain barrier (BBB) models can be useful for
      understanding leukocyte-endothelial interactions at this unique vascular-tissue
      interface. Desirable features of such a model include shear stress, non
      transformed cells and co-cultures of brain microvascular endothelial cells with
      astrocytes. Recovery of transmigrated leukocytes for further analysis is also
      appealing. NEW METHODS: We report an in vitro BBB model for leukocyte
      transmigration incorporating shear stress with co-culture of conditionally
      immortalized human endothelial cell line (hBMVEC) and human astrocyte cell line
      (hAST). Transmigrated leukocytes can be recovered for comparison with input and
      non-transmigrated cells. RESULT: hBMVEC and hAST exhibited physiological and
      morphological BBB properties when cocultured back-to-back on membranes. In
      particular, astrocyte processes protruded through 3 MUm membrane pores,
      terminating in close proximity to the hBMVEC with a morphology reminiscent of end
      feet. Co-culture with hAST also decreased the permeability of hBMVEC. In our
      model, astrocytes promoted transendothelial leukocyte transmigration. COMPARISON
      WITH EXISTING METHODS: This model offers the opportunity to evaluate whether BBB
      properties and leukocyte transmigration across cytokine-activated hBMVEC are
      influenced by human astrocytes. CONCLUSIONS: We present a BBB model for leukocyte
      transmigration incorporating shear stress with co-culture of hBMVEC and hAST. We
      demonstrate that hAST promoted leukocyte transmigration and also increased
      certain barrier functions of hBMVEC. This model provides reproducible assays for
      leukocyte transmigration with robust results, which will enable further defining
      the relationships among leukocytes and the cellular elements of the BBB.

PMID- 24858799
TI  - Images in anesthesiology: facemask ventilation with a frontonasal encephalocele.

PMID- 24858798
TI  - Methods for pulse artefact reduction: experiences with EEG data recorded at 9.4 T
      static magnetic field.
AB  - BACKGROUND: The feasibility of recording electroencephalography (EEG) at ultra
      high static magnetic fields up to 9.4 T was recently demonstrated and is expected
      to be incorporated into functional magnetic resonance imaging (fMRI) studies at
      9.4 T. Correction of the pulse artefact (PA) is a significant challenge since its
      amplitude is proportional to the strength of the magnetic field in which EEG is
      recorded. NEW METHOD: We conducted a study in which different PA correction
      methods were applied to EEG data recorded inside a 9.4 T scanner in order to
      retrieve visual P100 and auditory P300 evoked potentials. We explored different
      PA reduction methods, including the optimal basis set (OBS) method as well as
      objective and subjective component rejection using independent component analysis
      (ICA). RESULTS: ICA followed by objective rejection of components is optimal for
      retrieving visual P100 and auditory P300 from EEG data recorded inside the
      scanner. COMPARISON WITH EXISTING METHODS: Previous studies suggest that OBS or
      OBS followed by ICA are optimal for retrieving evoked potentials at 3T. In our
      EEG data recorded at 9.4 T OBS performed alone was not fully optimal for the
      identification of evoked potentials. OBS followed by ICA was partially effective.
      CONCLUSIONS: In this study ICA has been shown to be an important tool for
      correcting the PA in EEG data recorded at 9.4 T, particularly when automated
      rejection of components is performed.

PMID- 24858800
TI  - Cell sheet approach for tissue engineering and regenerative medicine.
AB  - After the biotech medicine era, regenerative medicine is expected to be an
      advanced medicine that is capable of curing patients with difficult-to-treat
      diseases and physically impaired function. Our original scaffold-free cell sheet
      based tissue engineering technology enables transplanted cells to be engrafted
      for a long time, while fully maintaining their viability. This technology has
      already been applied to various diseases in the clinical setting, including the
      cornea, esophagus, heart, periodontal ligament, and cartilage using autologous
      cells. Transplanted cell sheets not only replace the injured tissue and
      compensate for impaired function, but also deliver growth factors and cytokines
      in a spatiotemporal manner over a prolonged period, which leads to promotion of
      tissue repair. Moreover, the integration of stem cell biology and cell sheet
      technology with sufficient vascularization opens possibilities for fabrication of
      human three-dimensional vascularized dense and intact tissue grafts for
      regenerative medicine to parenchymal organs. 

PMID- 24858801
TI  - CXCL12/CXCR4 axis confers adriamycin resistance to human chronic myelogenous
      leukemia and oroxylin A improves the sensitivity of K562/ADM cells.
AB  - This study was aimed at investigating the reversal effect of oroxylin A, a
      naturally bioactive monoflavonoid separated and purified from Scutellaria
      baicalensis Georgi, in human chronic myeloid leukemia (CML) and the underlying
      mechanisms. The results showed that CXCL12 could enhance the resistance of K562
      cells to adriamycin (ADM) by increasing the expression of CXCR4, up-regulating
      the downstream PI3K/Akt pathway, and promoting translocation of NF-kappaB dimers
      into nucleus and subsequently decreasing the expression of apoptosis-related
      proteins in K562 cells. And we found that ADM resistance was partially reversed
      by CXCR4 siRNA transfection. Moreover, the sensitivity enhancement of oroxylin A
      was demonstrated by decreasing the expression of CXCR4 at both protein and mRNA
      levels, via PI3K/Akt/NF-kappaB pathway and triggering the apoptosis pathway in
      vitro. In addition, the in vivo study showed that oroxylin A increased apoptosis
      of leukemic cells with low systemic toxicity, and the mechanism was the same as
      in vitro study. In conclusion, all these results showed that oroxylin A improved
      the sensitivity of K562/ADM cells by increasing apoptosis in leukemic cells and
      decreasing the expression of CXCR4 and PI3K/Akt/NF-kappaB pathway, and probably
      served as a most promising agent for CML treatment.

PMID- 24858802
TI  - Autophagy inhibition switches low-dose camptothecin-induced premature senescence
      to apoptosis in human colorectal cancer cells.
AB  - Recently, several studies indicated that senescent tumor cells are resistant to
      apoptosis in chemotherapy. They may return to cell cycle, thus act as stumbling
      blocks in anticancer treatments. In the present study, we found that, in human
      colorectal cancer cells, low-dose camptothecin (CPT) simultaneously induced
      autophagy and premature senescence through AMPK-TSC2-mTOR pathway and ATM-Chk2
      p53-p21 pathway respectively. What's important is the suppression of autophagy
      substantially increased apoptosis and greatly attenuated senescence possibly by
      blocking p53/p21 pathway, which suggests that autophagy plays an indispensable
      role in sustaining cell senescence caused by low-dose CPT. The combination of low
      dose CPT and autophagy inhibitor, a way to lead senescent cells to die, would be
      potentially valuable in cancer therapy.

PMID- 24858803
TI  - Earthworm bioturbation influences the phytoavailability of metals released by
      particles in cultivated soils.
AB  - The influence of earthworm activity on soil-to-plant metal transfer was studied
      by carrying out six weeks mesocosms experiments with or without lettuce and/or
      earthworms in soil with a gradient of metal concentrations due to particles
      fallouts. Soil characteristics, metal concentrations in lettuce and earthworms
      were measured and soil porosity in the mesocosms was determined. Earthworms
      increased the soil pH, macroporosity and soil organic matter content due to the
      burying of wheat straw provided as food. Earthworm activities increased the
      metals concentrations in lettuce leaves. Pb and Cd concentrations in lettuce
      leaves can increase up to 46% with earthworm activities ... These results and the
      low correlation between estimated by CaCl2 and EDTA and measured pollutant
      phytoavailability suggest that earthworm bioturbation was the main cause of the
      increase. Bioturbation could affect the proximity of pollutants to the roots and
      soil organic matter. 

PMID- 24858804
TI  - Comparison of bioconcentration of ionic silver and silver nanoparticles in
      zebrafish eleutheroembryos.
AB  - The production of silver nanoparticles has reached nowadays high levels.
      Bioconcentration studies, information on persistence and toxicity are fundamental
      to assess their global risk and thus necessary to establish legislations
      regarding their use. Previous studies on silver nanoparticle toxicity have
      determined a clear correlation between their chemical stability and toxicity. In
      this work, experimental conditions able to assure silver nanoparticles stability
      have been optimized. Then, zebrafish (Danio rerio) eleutheroembryos were exposed
      to ionic silver and to Ag NPs for comparison purposes. A protocol alternative to
      the OECD 305 technical guideline was used. To determine silver concentration in
      both the eleutheroembryos and the exposure media, an analytical method consisting
      in ultrasound assisted extraction, followed by inductively coupled plasma mass
      spectrometry and graphite furnace atomic absorption spectrometry, was developed.
      Then, bioconcentration factors were calculated. The results revealed that ionic
      silver was more accumulative for zebrafish eleutheroembryos than nanoparticles at
      the levels tested. 

PMID- 24858805
TI  - Long-term hydrocephalus alters the cytoarchitecture of the adult subventricular
      zone.
AB  - Hydrocephalus can develop secondarily to a disturbance in production, flow and/or
      absorption of cerebrospinal fluid. Experimental models of hydrocephalus,
      especially subacute and chronic hydrocephalus, are few and limited, and the
      effects of hydrocephalus on the subventricular zone are unclear. The aim of this
      study was to analyze the effects of long-term obstructive hydrocephalus on the
      subventricular zone, which is the neurogenic niche lining the lateral ventricles.
      We developed a new method to induce hydrocephalus by obstructing the aqueduct of
      Sylvius in the mouse brain, thus simulating aqueductal stenosis in humans. In 120
      day-old rodents (n=18 per group), the degree of ventricular dilatation and
      cellular composition of the subventricular zone were studied by
      immunofluorescence and transmission electron microscopy. In adult patients
      (age>18years), the sizes of the subventricular zone, corpus callosum, and
      internal capsule were analyzed by magnetic resonance images obtained from
      patients with and without aqueductal stenosis (n=25 per group). Mice with 60-day
      hydrocephalus had a reduced number of Ki67+ and doublecortin+cells on
      immunofluorescence, as well as decreased number of neural progenitors and
      neuroblasts in the subventricular zone on electron microscopy analysis as
      compared to non-hydrocephalic mice. Remarkably, a number of extracellular matrix
      structures (fractones) contacting the ventricular lumen and blood vessels were
      also observed around the subventricular zone in mice with hydrocephalus. In
      humans, the widths of the subventricular zone, corpus callosum, and internal
      capsule in patients with aqueductal stenosis were significantly smaller than age
      and gender-matched patients without aqueductal stenosis. In summary,
      supratentorial hydrocephalus reduces the proliferation rate of neural progenitors
      and modifies the cytoarchitecture and extracellular matrix compounds of the
      subventricular zone. In humans, this similar process reduces the subventricular
      niche as well as the width of corpus callosum and internal capsule. 

PMID- 24858807
TI  - Pulmonary hypertension in wild type mice and animals with genetic deficit in
      KCa2.3 and KCa3.1 channels.
AB  - OBJECTIVE: In vascular biology, endothelial KCa2.3 and KCa3.1 channels contribute
      to arterial blood pressure regulation by producing membrane hyperpolarization and
      smooth muscle relaxation. The role of KCa2.3 and KCa3.1 channels in the pulmonary
      circulation is not fully established. Using mice with genetically encoded deficit
      of KCa2.3 and KCa3.1 channels, this study investigated the effect of loss of the
      channels in hypoxia-induced pulmonary hypertension. APPROACH AND RESULT: Male
      wild type and KCa3.1-/-/KCa2.3T/T(+DOX) mice were exposed to chronic hypoxia for
      four weeks to induce pulmonary hypertension. The degree of pulmonary hypertension
      was evaluated by right ventricular pressure and assessment of right ventricular
      hypertrophy. Segments of pulmonary arteries were mounted in a wire myograph for
      functional studies and morphometric studies were performed on lung sections.
      Chronic hypoxia induced pulmonary hypertension, right ventricular hypertrophy,
      increased lung weight, and increased hematocrit levels in either genotype. The
      KCa3.1-/-/KCa2.3T/T(+DOX) mice developed structural alterations in the heart with
      increased right ventricular wall thickness as well as in pulmonary vessels with
      increased lumen size in partially- and fully-muscularized vessels and decreased
      wall area, not seen in wild type mice. Exposure to chronic hypoxia up-regulated
      the gene expression of the KCa2.3 channel by twofold in wild type mice and
      increased by 2.5-fold the relaxation evoked by the KCa2.3 and KCa3.1 channel
      activator NS309, whereas the acetylcholine-induced relaxation - sensitive to the
      combination of KCa2.3 and KCa3.1 channel blockers, apamin and charybdotoxin - was
      reduced by 2.5-fold in chronic hypoxic mice of either genotype. CONCLUSION:
      Despite the deficits of the KCa2.3 and KCa3.1 channels failed to change hypoxia
      induced pulmonary hypertension, the up-regulation of KCa2.3-gene expression and
      increased NS309-induced relaxation in wild-type mice point to a novel mechanism
      to counteract pulmonary hypertension and to a potential therapeutic utility of
      KCa2.3/KCa3.1 activators for the treatment of pulmonary hypertension.

PMID- 24858808
TI  - The PDZ domain of the guanine nucleotide exchange factor PDZGEF directs binding
      to phosphatidic acid during brush border formation.
AB  - PDZGEF is a guanine nucleotide exchange factor for the small G protein Rap. It
      was recently found that PDZGEF contributes to establishment of intestinal
      epithelial polarity downstream of the kinase Lkb1. By binding to phosphatidic
      acid enriched at the apical membrane, PDZGEF locally activates Rap2a resulting in
      induction of brush border formation via a pathway that includes the polarity
      players TNIK, Mst4 and Ezrin. Here we show that the PDZ domain of PDZGEF is
      essential and sufficient for targeting PDZGEF to the apical membrane of polarized
      intestinal epithelial cells. Inhibition of PLD and consequently production of
      phosphatidic acid inhibitis targeting of PDZGEF to the plasma membrane.
      Furthermore, localization requires specific positively charged residues within
      the PDZ domain. We conclude that local accumulation of PDZGEF at the apical
      membrane during establishment of epithelial polarity is mediated by electrostatic
      interactions between positively charged side chains in the PDZ domain and
      negatively charged phosphatidic acid. 

PMID- 24858806
TI  - Low blood levels of sTWEAK are related to locoregional failure in head and neck
      cancer.
AB  - Identifying serum pre-treatment molecular markers that can predict response to
      therapy is of great interest in head and neck oncology and is required to develop
      personalized treatments that maximize survival while minimizing morbidity. The
      main aim was to investigate the potential prognostic significance of tumor
      necrosis factor-like weak inducer of apoptosis (TWEAK), and its receptors,
      fibroblast growth factor-inducible 14 (Fn14) and CD163, in head and neck squamous
      cell carcinoma (HNSCC). The study comprised 37 consecutive patients with
      pathologically confirmed, untreated HNSCC. Serum and tissue samples from these
      patients were available for study. We determined sTWEAK and sCD163 levels in
      serum from 37 HNSCC patients by ELISA. TWEAK, CD163, Fn14 and TNF-alpha gene
      expression were detected by real-time RT-PCR in 111 matched tissue samples
      (tumoral, adjacent and distal/normal mucosa). Our results showed a significant
      relationship between low sTWEAK levels and poor locoregional control of the
      disease. Kaplan-Meier curves indicated that the locoregional recurrence-free
      survival rate in patients with low sTWEAK circulating levels was significantly
      lower than in patients with high levels, and that high CD136/TWEAK expression
      ratio in tumors was also related to poor prognosis. sTWEAK pre-treatment serum
      levels might be used as prognostic non-invasive biomarkers for locoregional
      control in patients with HNSCC. Future investigations are warranted to determine
      the potential prognostic significance of this non-invasive biomarker in the rapid
      discrimination according to the locoregional control achieved in patients who
      received a non-surgical organ preservation treatment. 

PMID- 24858809
TI  - Non-essential amino acids attenuate apoptosis of gastric cancer cells induced by
      glucose starvation.
AB  - Energy and nutrition are essential requirements for all living cells, including
      cancer cells. In the initiating stage of cancer in organs, cancer cells grow fast
      and have inadequate supplies of glucose, oxygen and other nutrients due to
      deficient angiogenesis. Anaerobic conditions cause cancer cells to rely on
      glycolysis, which produces pyruvate and ATP that can be used by cancer cells to
      survive. However, glucose starvation may result in apoptosis or necrosis of
      cancer cells. It has been reported that autophagy is a consequence of glucose
      starvation and that amino acids are products of autophagy. The present study
      investigated whether amino acids may represent an alternative energy source for
      cancer cells undergoing glucose starvation. With non-essential amino acids,
      growth inhibition and apoptosis of gastric cancer cells induced by glucose
      starvation were attenuated compared with that of cells undergoing glucose
      starvation without amino acids, as measured by cell viability, apoptosis rates,
      membrane potential of mitochondria, and apoptosis-related genes. Meanwhile, both
      mitochondrial DNA copy number and amino acid transporter genes were increased
      compared with those in control cells. Non-essential amino acids prevented gastric
      cancer cells from glucose starvation-induced apoptosis. 

PMID- 24858810
TI  - Genome wide association study identifies 20 novel promising genes associated with
      milk fatty acid traits in Chinese Holstein.
AB  - Detecting genes associated with milk fat composition could provide valuable
      insights into the complex genetic networks of genes underling variation in fatty
      acids synthesis and point towards opportunities for changing milk fat composition
      via selective breeding. In this study, we conducted a genome-wide association
      study (GWAS) for 22 milk fatty acids in 784 Chinese Holstein cows with the PLINK
      software. Genotypes were obtained with the Illumina BovineSNP50 Bead chip and a
      total of 40,604 informative, high-quality single nucleotide polymorphisms (SNPs)
      were used. Totally, 83 genome-wide significant SNPs and 314 suggestive
      significant SNPs associated with 18 milk fatty acid traits were detected.
      Chromosome regions that affect milk fatty acid traits were mainly observed on
      BTA1, 2, 5, 6, 7, 9, 13, 14, 18, 19, 20, 21, 23, 26 and 27. Of these, 146 SNPs
      were associated with more than one milk fatty acid trait; most of studied fatty
      acid traits were significant associated with multiple SNPs, especially C18:0 (105
      SNPs), C18 index (93 SNPs), and C14 index (84 SNPs); Several SNPs are close to or
      within the DGAT1, SCD1 and FASN genes which are well-known to affect milk
      composition traits of dairy cattle. Combined with the previously reported QTL
      regions and the biological functions of the genes, 20 novel promising candidates
      for C10:0, C12:0, C14:0, C14:1, C14 index, C18:0, C18:1n9c, C18 index, SFA, UFA
      and SFA/UFA were found, which composed of HTR1B, CPM, PRKG1, MINPP1, LIPJ, LIPK,
      EHHADH, MOGAT1, ECHS1, STAT1, SORBS1, NFKB2, AGPAT3, CHUK, OSBPL8, PRLR, IGF1R,
      ACSL3, GHR and OXCT1. Our findings provide a groundwork for unraveling the key
      genes and causal mutations affecting milk fatty acid traits in dairy cattle. 

PMID- 24858811
TI  - Ranolazine ameliorates postresuscitation electrical instability and myocardial
      dysfunction and improves survival with good neurologic recovery in a rat model of
      cardiac arrest.
AB  - BACKGROUND: During ischemia, enhancement of the "late Na+ current" (I(NaL))
      contributes to intracellular Ca2+ overload. Dysregulation of intracellular Ca2+
      homeostasis plays a critical role in the pathophysiology of cardiac arrest and
      cardiopulmonary resuscitation (CPR), leading to ventricular arrhythmias and left
      ventricle (LV) dysfunction. OBJECTIVE: The purpose of this study was to
      investigate the effects of the I(NaL) blocker ranolazine on outcome of CPR in a
      rat model. We hypothesized that ranolazine might reduce postresuscitation
      arrhythmias and improve survival and recovery. METHODS: Eighteen rats were
      assigned to receive intravenous ranolazine 10 mg/kg or vehicle. Ventricular
      fibrillation was induced and untreated for 8 minutes. CPR then was performed for
      8 minutes. ECG and arterial and right atrial pressures were monitored up to 3
      hours after CPR. After resuscitation, LV function was monitored by
      echocardiography, and 72-hour survival with neurologic recovery was evaluated.
      Plasma was obtained for biomarkers of heart and brain injury. RESULTS: All
      animals in the ranolazine group were resuscitated and survived up to 72 hours,
      whereas 72% in the vehicle group were resuscitated but 54% survived. The period
      of postresuscitation arrhythmia with hemodynamic instability was shorter in the
      ranolazine group compared to vehicle group (P < .02). Seventy-two hours after
      resuscitation, LV systolic and diastolic functions were better in the ranolazine
      group compared to vehicle (P < .05). Full neurologic recovery was observed in all
      ranolazine animals, whereas neurologic impairment persisted in the vehicle group
      (P < .02). CONCLUSION: In this model, ranolazine pretreatment reduced
      postresuscitation electrical and hemodynamic instability and improved 72-hour
      postresuscitation LV function and survival with good neurologic recovery.

PMID- 24858812
TI  - Early repolarization as a predictor of arrhythmic and nonarrhythmic cardiac
      events in middle-aged subjects.
AB  - BACKGROUND: Early repolarization (ER) in the inferior/lateral leads predicts
      mortality, but whether ER is a specific sign of increased risk for arrhythmic
      events is not known. OBJECTIVE: The purpose of this study was to study the
      association of ER and arrhythmic events and nonarrhythmic morbidity and
      mortality. METHODS: We assessed the prognostic significance of ER in a community
      based general population of 10,846 middle-aged subjects (mean age 44 +/- 8
      years). The end-points were sustained ventricular tachycardia or resuscitated
      ventricular fibrillation (VT-VF), arrhythmic death, nonarrhythmic cardiac death,
      new-onset atrial fibrillation (AF), hospitalization for congestive heart failure,
      or coronary artery disease during mean follow-up of 30 +/- 11 years. ER was
      defined as >=0.1-mV elevation of J point in either inferior or lateral leads.
      RESULTS: After including all risk factors of cardiac mortality and morbidity in
      Cox regression analysis, inferior ER (prevalence 3.5%) predicted VF-VT events (n
      = 108 [1.0%]) with a hazard ratio (HR) of 2.2 (95% confidence interval [CI] 1.1
      4.5, P = .03) but not nonarrhythmic cardiac death (n = 1235 [12.2%]), AF (n =
      1659 [15.2%]), congestive heart failure (n = 1752 [16.1%]), or coronary artery
      disease (n = 3592 [32.9%]) (P = NS for all). Inferior ER predicted arrhythmic
      death in cases without other QRS complex abnormalities (multivariate HR 1.68, 95
      % CI 1.10-2.58, P = .02) but not in those with ER and other coexisting
      abnormalities in QRS morphology (HR 1.30, 95% CI 0.86-1.96, P = .22). CONCLUSION:
      ER in the inferior leads, especially in cases without other QRS complex
      abnormalities, predicts the occurrence of VT-VF but not nonarrhythmic cardiac
      events, suggesting that ER is a specific sign of increased vulnerability to
      ventricular tachyarrhythmias.

PMID- 24858813
TI  - Impact of left atrial appendage morphology on peri-interventional thromboembolic
      risk during catheter ablation of atrial fibrillation.
AB  - BACKGROUND: Left atrial appendage (LAA) morphology recently has been suggested to
      influence thromboembolic risk in patients with atrial fibrillation (AF).
      OBJECTIVE: The purpose of this study was to examine the impact of LAA morphology
      on peri-interventional thromboembolic events in patients undergoing AF catheter
      ablation. METHODS: Of 2570 consecutive patients undergoing AF ablation, 17
      patients with cerebral thromboembolic events within 30 days of AF ablation were
      selected and matched for CHA2DS2VASc score, peri-interventional anticoagulation,
      and procedural characteristics with 68 event-free patients. LAA morphology was
      visualized by cardiac computed tomography and classified into 4 types: cactus,
      chicken wing, windsock, and cauliflower. RESULTS: Baseline, echocardiographic,
      and procedural characteristics of both patient groups were similar. Patients with
      embolic complications had a significantly higher incidence of chicken wing
      morphology compared to event-free controls (65% vs. 21% chicken wing, 18% vs. 24%
      cactus, 12% vs. 13% windsock, 5% vs. 42% cauliflower, respectively, P < .001),
      which translates into a >7* higher risk compared to other morphologies (odds
      ratio 7.2, 95% confidence interval 1.353-38.328, P = .021) when adjusted for
      possible confounders associated with chicken wing morphology. CONCLUSION: LAA
      chicken wing morphology is associated with higher periprocedural thromboembolic
      risk in patients undergoing AF ablation. Further studies are needed to determine
      the mechanisms and possible implications of this observation.

PMID- 24858815
TI  - Body burden of Hg in different bio-samples of mothers in Shenyang city, China.
AB  - Hg is an accumulative and neuro-toxic heavy metal which has a wide range of
      adverse effects in human health. However, few studies are available on body
      burden of Hg level in different bio-samples of pregnant women in Chinese
      population. Therefore, this study evaluated Hg levels in different maternal bio
      samples in Shenyang city, China and investigated the correlation of Hg levels in
      different bio-samples. From October to December 2008, 200 pregnant women about to
      deliver their babies at ShengJing Hospital (Shenyang city, northeast of China)
      participated in this study. The geometric mean (GM) of Hg levels in cord blood,
      maternal venous blood, breast milk, and maternal urine were 2.18 ug/L, 1.17 ug/L,
      1.14 ug/L, and 0.73 ug/L, respectively, and the GM of maternal hair Hg level was
      404.45 ug/kg. There was a strong correlation between cord blood and maternal
      blood total Hg level (r = 0.713, P<0.001). Frequency of fish consumption more
      than or equal to 3 times per week during pregnancy was suggested as a significant
      risk factor of prenatal Hg exposure (unadjusted OR 3.5, adjusted OR 2.94,
      P<0.05). This study provides evidence about Hg burden of mothers and the risk
      factors of prenatal Hg exposure in Shenyang city, China. 

PMID- 24858816
TI  - Distinct promoters affect pyrroloquinoline quinone production in recombinant
      Escherichia coli and Klebsiella pneumoniae.
AB  - Pyrroloquinoline quinone (PQQ) is a versatile quinone cofactor participating in
      numerous biological processes. Klebsiella pneumoniae can naturally synthesize PQQ
      for harboring intact PQQ synthesis genes. Previous metabolic engineering of K.
      pneumoniae failed to overproduce PQQ due to the employment of strong promoter in
      expression vector. Here we report that a moderate rather than strong promoter is
      efficient for PQQ production. To screen an appropriate promoter, a total of four
      distinct promoters-lac promoter, pk promoter of glycerol dehydratase gene
      (dhaB1), promoter of kanamycin resistance gene, and T7 promoter (as the control)
      were individually used for overexpressing the endogenous PQQ genes in K.
      pneumoniae along with heterologous expression in Escherichia coli. We found that
      all recombinant K. pneumoniae strains produced more PQQ than recombinant E. coli
      strains that carried corresponding vectors, indicating that K. pneumoniae is
      superior to E. coli for the production of PQQ. Particularly, the recombinant K.
      pneumoniae recruiting the promoter of kanamycin resistance gene produced the
      highest PQQ (1,700 nmol), revealing that a moderate rather than strong promoter
      is efficient for PQQ production. Furthermore, PQQ production was roughly
      proportional to glucose concentration increasing from 0.5 to 1.5 g/L, implying
      the synergism between PQQ biosynthesis and glucose utilization. This study not
      only provides a feasible strategy for production of PQQ in K. pneumoniae, but
      also reveals the exquisite synchronization among PQQ biosynthesis, glucose
      metabolism, and cell proliferation. 

PMID- 24858817
TI  - Phlegmasia cerulea dolens: before and after lysis.

PMID- 24858818
TI  - DOT1L inhibition sensitizes MLL-rearranged AML to chemotherapy.
AB  - DOT1L, the only known histone H3-lysine 79 (H3K79) methyltransferase, has been
      shown to be essential for the survival and proliferation of mixed-linkage
      leukemia (MLL) gene rearranged leukemia cells, which are often resistant to
      conventional chemotherapeutic agents. To study the functions of DOT1L in MLL
      rearranged leukemia, SYC-522, a potent inhibitor of DOT1L developed in our
      laboratory, was used to treat MLL-rearranged leukemia cell lines and patient
      samples. SYC-522 significantly inhibited methylation at H3K79, but not H3K4 or
      H3K27, and decreased the expression of two important leukemia-relevant genes,
      HOXA9 and MEIS1, by more than 50%. It also significantly reduced the expression
      of CCND1 and BCL2L1, which are important regulators of cell cycle and anti
      apoptotic signaling pathways. Exposure of MLL-rearranged leukemia cells to this
      compound caused cell cycle arrest and promoted differentiation of those cells,
      both morphologically and by increased CD14 expression. SYC-522 did not induce
      apoptosis, even at 10 uM for as long as 6 days. However, treatment with this
      DOT1L inhibitor decreased the colony formation ability of primary MLL-rearranged
      AML cells by up to 50%, and promoted monocytic differentiation. Notably, SYC-522
      treatment significantly increased the sensitivity of MLL-rearranged leukemia
      cells to chemotherapeutics, such as mitoxantrone, etoposide and cytarabine. A
      similar sensitization was seen with primary MLL-rearranged AML cells. SYC-522 did
      not affect chemotherapy-induced apoptosis in leukemia cells without MLL
      rearrangement. Suppression of DOT1L activity inhibited the mitoxantrone-induced
      increase in the DNA damage response marker, gammaH2AX, and increased the level of
      cPARP, an intracellular marker of apoptosis. These results demonstrated that SYC
      522 selectively inhibited DOT1L, and thereby altered gene expression, promoted
      differentiation, and increased chemosensitivity by preventing DNA damage
      response. Therefore, inhibition of DOT1L, in combination with DNA damaging
      chemotherapy, represents a promising approach to improving outcomes for MLL
      rearranged leukemia. 

PMID- 24858819
TI  - Wnt signaling transcription factors TCF-1 and LEF-1 are upregulated in malignant
      astrocytic brain tumors.
AB  - Since the discovery of the TCF/LEF family of transcription factors, their
      functions have been under intensive investigation in the area of cancer biology.
      The work presented in this paper focused on the changes in TCF-1 and LEF-1
      expression levels in a set of astrocytic brain tumors. Protein expression was
      detected using immunohistochemistry and then evaluated by Ellipse software
      (ViDiTo, Slovakia). Statistical evaluations were performed with the SPSS
      statistical package, version 14.0 (SPSS Inc., Chicago, IL, USA). Strong TCF-1 and
      LEF-1 expression was observed in 51.6% and 71% of glioblastoma samples.
      Statistical analysis confirmed significant differences in protein expression
      levels associated to 3 important values, weak expression of TCF-1, weak
      expression of LEF-1 and strong expression of LEF-1. Analysis of variances
      performed on the total sample also indicated significant differences in the
      values of TCF-1 weak (F=2.804; p=0.045), LEF-1 weak (F=4.255; p=0.008) and LEF-1
      strong (F=5.498; p=0.002) with regard to malignancy grade. Thus, glioblastomas
      were characterized by -in relative terms- the lowest values for weak expression
      of TCF-1 and LEF-1, combined with the highest values of LEF-1 strong expression.
      The F-ratios for two variables (LEF-1 strong and LEF-1 weak) indicated that
      differences between astrocytomas (II, III) and glioblastomas were statistically
      significant (p<0.02). Discriminant function analysis further showed that strong
      LEF-1 expression alone could discriminate between astrocytomas (II, III) and
      glioblastomas. Elevated TCF-1 and LEF-1 expression is characteristic of malignant
      gliomas. LEF-1, in particular, may serve as a potential marker for malignant
      transformation.

PMID- 24858820
TI  - Bevacizumab increases the risk of gastrointestinal perforation in cancer
      patients: a meta-analysis with a focus on different subgroups.
AB  - BACKGROUND: The aim of this meta-analysis was to gather current data and evaluate
      not only the risk of gastrointestinal (GI) perforation with bevacizumab, but also
      the potential risk factors for this adverse event. MATERIALS AND METHODS: We
      carried out a literature search in PubMed for randomized controlled trials (RCTs)
      reported from January 2000 to December 2013. Summary incidence, relative risks
      (RRs) and 95% confidence intervals (CIs) were calculated using random-effects or
      fixed-effects models based on the heterogeneity of the included studies. RESULTS:
      A total of 26,833 patients from 33 RCTs were included in the meta-analysis.
      Bevacizumab-containing therapy significantly increased the risk of developing all
      grade (RR 3.35, 95% CI 2.35-4.79, P < 0.001) and fatal GI perforation (RR 3.08,
      95%CI: 1.04-9.08, P = 0.042). On subgroup analysis, no significant risk
      differences were found based on bevacizumab dosage, treatment duration, treatment
      line, type of clinical trial and median age. When stratified by tumor types, a
      significantly increased risk of GI perforation with bevacizumab was observed in
      colorectal cancer (RR 2.84, 95% CI 1.43-5.61, P = 0.003), gynecologic cancer (RR
      3.37, 95% CI 1.71-6.62, P < 0.001) and prostate cancer (RR 6.01, 95% CI 1.78
      20.28, P = 0.004). Additionally, the use of bevacizumab significantly increased
      the risk of GI perforation when used in conjunction with taxanes (RR 3.09, 95% CI
      1.92-4.96, P < 0.001) or oxaliplatin (RR 2.85, 95% CI 1.07-7.57, P = 0.036).
      CONCLUSIONS: Bevacizumab treatment is associated with a significantly increased
      risk of developing GI perforation, and clinicians should be aware of the risks of
      GI perforation with the administration of this drug in cancer patients.

PMID- 24858821
TI  - Cloxacillin concentrations in serum, subcutaneous fat, and muscle in patients
      with chronic critical limb ischemia.
AB  - BACKGROUND: Patients suffering from critical limb ischemia (CLI) have poor wound
      healing in the ankle and foot areas. Secondary wound infections are frequent and
      often treated with prolonged courses of antibiotics. PURPOSE: This study set out
      to investigate to what extent the unbound fraction of 4 g of cloxacillin i.v.
      reaches its target organ in poorly vascularized tissues, i.e., the calf and foot
      of patients suffering from CLI. METHODS: Cloxacillin concentrations were measured
      by HPLC in serum and in microdialysis samples from skin and muscle of the lower
      part of the calf and as reference subcutaneously at the pectoral level in eight
      patients suffering from CLI (four males, four females, mean age 78 years, range
      66-85 years) and in three healthy controls (two females, one male, mean age 67,
      range 66-68 years). RESULTS: In patients suffering from CLI, the tissue
      penetration of cloxacillin after a single 4 g dose was comparable to that of
      healthy controls, despite impaired blood circulation. CONCLUSIONS: The reduced
      blood flow in the peripheral vessels of the CLI patients presented here
      apparently is not the rate-limiting factor for delivery or tissue penetration of
      cloxacillin.

PMID- 24858822
TI  - Impact of age on serum concentrations of venlafaxine and escitalopram in
      different CYP2D6 and CYP2C19 genotype subgroups.
AB  - PURPOSE: The aim of the present study was to investigate the effect of age on
      venlafaxine and escitalopram serum concentrations in various cytochrome P450
      (CYP) 2D6 and CYP2C19 genotype subgroups. METHODS: Serum concentration
      measurements from CYP-genotyped patients treated with venlafaxine (n = 255) or
      escitalopram (n = 541) were collected retrospectively from a therapeutic drug
      monitoring database. Patients were divided into three CYP2D6 (venlafaxine) or
      CYP2C19 (escitalopram) phenotype subgroups according to inherited genotype, i.e.,
      poor metabolizers (PMs), heterozygous extensive metabolizers (HEMs), and
      extensive metabolizers (EMs), and subsequently distributed into three age groups,
      i.e., <40 (control), 40-65, and >65 years. The effect of age on dose-adjusted
      serum concentrations (i.e., nmol/L/mg/day) of venlafaxine and escitalopram in
      each of the phenotype subgroups was evaluated by separate multivariate mixed
      model analyses. RESULTS: In CYP2D6 PMs, the mean dose-adjusted serum
      concentration of venlafaxine was 8-fold higher in patients >65 years compared
      with those <40 years (p < 0.001). In comparison, the respective age-related
      differences in mean dose-adjusted serum concentrations of venlafaxine were much
      less pronounced in CYP2D6 HEMs and EMs (<2-fold differences between age groups).
      A similar genotype-related effect of age was not observed for escitalopram (<1.5
      fold age differences in all CYP2C19 subgroups). CONCLUSION: This study suggests
      that the effect of age on serum concentration of venlafaxine is dependent on CYP
      genotype, in contrast to escitalopram. Thus, to prevent potential side effects,
      it might be particularly relevant to consider CYP2D6 genotyping prior to
      initiation of venlafaxine treatment in older patients.

PMID- 24858823
TI  - Use of rivaroxaban in Germany: a database drug utilization study of a drug
      started in hospital.
AB  - PURPOSE: The purpose of this drug utilization study was to describe the use of
      rivaroxaban in Germany during a time period in which approval was limited to the
      prevention of venous thromboembolism following hip or knee replacement.
      Additionally, we explored the feasibility of reconstructing inpatient drug use of
      rivaroxaban in a database where with a few exceptions inpatient prescribing
      information is not available. METHODS: Source of data was one statutory health
      insurance providing data on about seven million insurants throughout Germany.
      Analyses were based on a cohort of rivaroxaban users from launch (October 2008)
      to December 2009 and encompassed potential indications for rivaroxaban use,
      treatment duration, and co-prescribing of potentially interacting drugs. Start of
      rivaroxaban treatment was defined by the date of surgery. RESULTS: During the
      study period, 425 rivaroxaban users were identified contributing 440 treatment
      periods. For more than 82% of these episodes labelled indications could be
      determined. Treatment durations exceeded recommendations in 95% of the episodes
      following knee replacement whereas rivaroxaban use after elective hip surgery was
      found to be longer than recommended in 56%. Prescribing of potentially
      interacting medication was rare except for non-steroidal anti-inflammatory drugs.
      CONCLUSIONS: Overall, no important off-label use of rivaroxaban was identified.
      Based on several assumptions that have to be considered in the interpretation of
      the results our study describes a database approach to reconstruct inpatient drug
      use for a drug started after a coded hospital procedure, when treatment continues
      after hospital discharge and no change in drug use is expected in the outpatient
      setting.

PMID- 24858826
TI  - Inorganic nitrogen leaching from organic and conventional rice production on a
      newly claimed calciustoll in Central Asia.
AB  - Characterizing the dynamics of nitrogen (N) leaching from organic and
      conventional paddy fields is necessary to optimize fertilization and to evaluate
      the impact of these contrasting farming systems on water bodies. We assessed N
      leaching in organic versus conventional rice production systems of the Ili River
      Valley, a representative aquatic ecosystem of Central Asia. The N leaching and
      overall performance of these systems were measured during 2009, using a
      randomized block experiment with five treatments. PVC pipes were installed at
      soil depths of 50 and 180 cm to collect percolation water from flooded organic
      and conventional paddies, and inorganic N (NH4-N+NO3-N) was analyzed. Two high
      concentration peaks of NH4-N were observed in all treatments: one during early
      tillering and a second during flowering. A third peak at the mid-tillering stage
      was observed only under conventional fertilization. NO3-N concentrations were
      highest at transplant and then declined until harvest. At the 50 cm soil depth,
      NO3-N concentration was 21-42% higher than NH4-N in percolation water from
      organic paddies, while NH4-N and NO3-N concentrations were similar for the
      conventional and control treatments. At the depth of 180 cm, NH4-N and NO3-N were
      the predominant inorganic N for organic and conventional paddies, respectively.
      Inorganic N concentrations decreased with soil depth, but this attenuation was
      more marked in organic than in conventional paddies. Conventional paddies leached
      a higher percentage of applied N (0.78%) than did organic treatments (0.32
      0.60%), but the two farming systems leached a similar amount of inorganic N per
      unit yield (0.21-0.34 kg N Mg(-1) rice grains). Conventional production showed
      higher N utilization efficiency compared to fertilized organic treatments. These
      results suggest that organic rice production in the Ili River Valley is unlikely
      to reduce inorganic N leaching, if high crop yields similar to conventional rice
      production are to be maintained.

PMID- 24858824
TI  - The use of the EVITA algorithm for clinical assessment of novel agents used in
      prostate cancer, metastatic melanoma, and systemic lupus erythematosus.
AB  - PURPOSE: Existing health technology assessment methods can be time-consuming and
      complicated to use in practice. EValuation of pharmaceutical Innovations with
      regard to Therapeutic Advantage (EVITA) is a recently developed drug assessment
      strategy that provides a detailed and clinically relevant evaluation of new
      agents compared to standard therapies. We therefore sought to use EVITA to
      evaluate eight novel agents recently introduced to clinical practice or in late
      stage trials for the treatment of prostate cancer, metastatic melanoma, or
      systemic lupus erythematosus (SLE). METHODS: Eight agents (abiraterone,
      enzalutamide, sipuleucel-T, Prostvac, radium 223, ipilimumab, vemurafenib, and
      belimumab) were selected for study using the EVITA algorithm. A comprehensive
      literature search was performed to find clinical trial data, which were then
      classified using the EVITA protocol. EVITA was also compared to results from
      health technology assessments (HTAs) or reimbursement decisions. RESULTS: The
      EVITA scores for the eight drugs ranged from 5.5 to 9: all the selected agents
      are therefore classed as 'recommended' and are likely to produce a therapeutic
      advantage. In particular, vemurafenib is likely to be highly beneficial to
      patients with metastatic melanoma and radium 223 to patients with metastatic
      prostate cancer affecting the bone. The EVITA results were generally concordant
      with HTAs. CONCLUSIONS: All the agents show favourable EVITA scores and are
      therefore recommended for clinical practice. EVITA is an easy-to-use tool that
      provides clinical context to the assessment of newly introduced agents and can be
      easily used by non-specialists.

PMID- 24858827
TI  - Reversal of multidrug resistance in vitro and in vivo by 5-N-formylardeemin, a
      new ardeemin derivative.
AB  - Because multidrug resistance (MDR) is a serious impediment to the use of
      chemotherapy in treating cancer patients, great efforts have been made to search
      for effective MDR-reversing agents. We have developed a brand new synthetic
      ardeemin derivative, 5-N-formylardeemin, and investigated the activity of which
      in reversing MDR in MDR cancer cell lines derived from human breast cancer (MCF-7
      R) or lung cancer (A549-R). 5-N-formylardeemin strongly enhanced the anti-cancer
      efficacy of doxorubicin, vincristine through potentiation of apoptosis in both
      MCF-7-R and A549-R at relatively noncytotoxic concentrations in vitro.
      Mechanistic studies showed that 5-N-formylardeemin inhibited the expression of
      MDR-1 (P-gp) and increased the intracellular accumulation of cytotoxic drugs in
      the MDR cells, suggesting that 5-N-formylardeemin reverses MDR activities through
      inhibiting MDR-1 expression. Interestingly, 5-N-formylardeemin also sensitized
      the parent wild-type cancer cells toward these chemotherapeutic agents to various
      extents. Importantly, in vivo studies demonstrated that 5-N-formylardeemin
      significantly improved the therapeutic effects of doxorubicin in nude mice
      bearing A549-R xenografts, which was associated with reduced expression of MDR-1
      protein level and increased apoptosis in tumor tissues. These results underscore
      5-N-formylardeemin as a potential sensitizer for chemotherapy against multidrug
      resistant cancers.

PMID- 24858829
TI  - Atrial fibrillation ablation: a death-defying endeavor?

PMID- 24858828
TI  - Transmembrane recognition of the semaphorin co-receptors neuropilin 1 and plexin
      A1: coarse-grained simulations.
AB  - The cancer associated class 3 semaphorins require direct binding to neuropilins
      and association to plexins to trigger cell signaling. Here, we address the role
      of the transmembrane domains of neuropilin 1 and plexin A1 for the dimerization
      of the two receptors by characterizing the assembly in lipid bilayers using
      coarse-grained molecular dynamics simulations. From experimental evidence using a
      two-hybrid system showing the biochemical association of the two receptors
      transmembrane domains, we performed molecular simulations in DOPC and POPC
      demonstrating spontaneously assembly to form homodimers and heterodimers with a
      very high propensity for right-handed packing of the helices. Inversely, left
      handed packing was observed with a very low propensity. This mode of packing was
      observed uniquely when the plexin A1 transmembrane domain was involved in
      association. Potential of mean force calculations were used to predict a
      hierarchy of self-association for the monomers: the two neuropilin 1
      transmembrane domains strongly associated, neuropilin 1 and plexin A1
      transmembrane domains associated less and the two plexin A1 transmembrane domains
      weakly but significantly associated. We demonstrated that homodimerization and
      heterodimerization are driven by GxxxG motifs, and that the sequence context
      modulates the packing mode of the plexin A1 transmembrane domains. This work
      presents major advances towards our understanding of membrane signaling platforms
      assembly through membrane domains and provides exquisite information for the
      design of antagonist drugs defining a novel class of therapeutic agents. 

PMID- 24858830
TI  - Pacemaker implantation for treatment of symptomatic atrioventricular conduction
      block caused by a vagus nerve stimulator.

PMID- 24858831
TI  - How many effects can dance on the head of a SNP?

PMID- 24858833
TI  - Turning eating psychopathology risk factors into action. The pervasive effect of
      body image-related cognitive fusion.
AB  - Body image dissatisfaction and unfavourable social comparisons are significant
      risk factors to eating psychopathology. Nevertheless, the impact of these
      negative experiences depends on the cognitive and emotional processes involved.
      Previous research has shown that cognitive fusion is a nuclear process linked to
      psychological inflexibility, but its role on body image and eating difficulties
      remains unclear. This study aims to explore a model of the mediational role of
      body image-related cognitive fusion (CF-BI) on the relationship between body
      dissatisfaction, unfavourable social comparisons, and eating psychopathology in a
      sample of 345 female students. Results from path analyses show that the impact of
      unfavourable social comparisons on eating psychopathology is fully mediated by CF
      BI. Moreover, CF-BI also revealed a mediational effect on the relationship
      between body image dissatisfaction and the severity of eating symptoms, in spite
      of the fact that a direct effect of body dissatisfaction still exists. The tested
      model highlights the crucial role that cognitive fusion, in the specific domain
      of body image, plays in the relationship between risk factors and the severity of
      disordered eating attitudes and behaviours. Furthermore, these findings present
      empirical support for the relevance of addressing acceptance and cognitive
      defusion techniques to prevent and treat eating disorders. 

PMID- 24858832
TI  - beta-Cryptoxanthin alleviates diet-induced nonalcoholic steatohepatitis by
      suppressing inflammatory gene expression in mice.
AB  - Recent nutritional epidemiological surveys showed that serum beta-cryptoxanthin
      inversely associates with the risks for insulin resistance and liver dysfunction.
      Consumption of beta-cryptoxanthin possibly prevents nonalcoholic steatohepatitis
      (NASH), which is suggested to be caused by insulin resistance and oxidative
      stress from nonalcoholic fatty liver disease. To evaluate the effect of beta
      cryptoxanthin on diet-induced NASH, we fed a high-cholesterol and high-fat diet
      (CL diet) with or without 0.003% beta-cryptoxanthin to C56BL/6J mice for 12
      weeks. After feeding, beta-cryptoxanthin attenuated fat accumulation, increases
      in Kupffer and activated stellate cells, and fibrosis in CL diet-induced NASH in
      the mice. Comprehensive gene expression analysis showed that although beta
      cryptoxanthin histochemically reduced steatosis, it was more effective in
      inhibiting inflammatory gene expression change in NASH. beta-Cryptoxanthin
      reduced the alteration of expression of genes associated with cell death,
      inflammatory responses, infiltration and activation of macrophages and other
      leukocytes, quantity of T cells, and free radical scavenging. However, it showed
      little effect on the expression of genes related to cholesterol and other lipid
      metabolism. The expression of markers of M1 and M2 macrophages, T helper cells,
      and cytotoxic T cells was significantly induced in NASH and reduced by beta
      cryptoxanthin. beta-Cryptoxanthin suppressed the expression of lipopolysaccharide
      (LPS)-inducible and/or TNFalpha-inducible genes in NASH. Increased levels of the
      oxidative stress marker thiobarbituric acid reactive substances (TBARS) were
      reduced by beta-cryptoxanthin in NASH. Thus, beta-cryptoxanthin suppresses
      inflammation and the resulting fibrosis probably by primarily suppressing the
      increase and activation of macrophages and other immune cells. Reducing oxidative
      stress is likely to be a major mechanism of inflammation and injury suppression
      in the livers of mice with NASH. 

PMID- 24858834
TI  - Carbohydrate in the mouth enhances activation of brain circuitry involved in
      motor performance and sensory perception.
AB  - The presence of carbohydrate in the human mouth has been associated with the
      facilitation of motor output and improvements in physical performance. Oral
      receptors have been identified as a potential mode of afferent transduction for
      this novel form of nutrient signalling that is distinct from taste. In the
      current study oral exposure to carbohydrate was combined with a motor task in a
      neuroimaging environment to identify areas of the brain involved in this
      phenomenon. A mouth-rinsing protocol was conducted whilst carbohydrate (CHO) and
      taste-matched placebo (PLA) solutions were delivered and recovered from the
      mouths of 10 healthy volunteers within a double-blind, counterbalanced design.
      This protocol eliminates post-oral factors and controls for the perceptual
      qualities of solutions. Functional magnetic resonance imaging of the brain was
      used to identify cortical areas responsive to oral carbohydrate during rest and
      activity phases of a hand-grip motor task. Mean blood-oxygen-level dependent
      signal change experienced in the contralateral primary sensorimotor cortex was
      larger for CHO compared with PLA during the motor task when contrasted with a
      control condition. Areas of activation associated with CHO exclusively were
      observed over the primary taste cortex and regions involved in visual perception.
      Regions in the limbic system associated with reward were also significantly more
      active with CHO. This is the first demonstration that oral carbohydrate
      signalling can increase activation within the primary sensorimotor cortex during
      physical activity and enhance activation of neural networks involved in sensory
      perception. 

PMID- 24858835
TI  - Parental encouragement of dieting promotes daughters' early dieting.
AB  - Dieting to lose weight is common among female adolescents. This research
      investigated the association between maternal and paternal encouragement to diet
      and their daughters' self-reported "early dieting" (prior to age 11 y) and
      adolescent dieting (between 11 y and 15 y), and how parental encouragement to
      diet is related to changes in daughters' BMI percentiles. Participants in this
      study were 174 non-Hispanic white girls and their parents, assessed when
      daughters were 9-, 11-, 13-, and 15 y. The Parent Encouragement of Child Weight
      Loss Scale was used to measure encouragement to diet. Logistic regression was
      used to examine the relationship between parental encouragement to diet and
      daughters' reports of dieting by 11 y and by 15 y, adjusting for daughters'
      weight status at baseline. Compared with girls whose mothers didn't encourage
      dieting, girls who were encouraged to diet were twice as likely to diet by 11 y;
      girls who were encouraged by their fathers were also twice as likely to diet by
      11 y. Girls who were encouraged to diet by both parents were 8 times more likely
      to report early dieting than girls who were not. Neither maternal nor paternal
      encouragement predicted the emergence of dieting during adolescence. Girls who
      dieted and had parental encouragement to do so had increases in BMI percentile
      from 9 y to 15 y. Findings reveal that parental encouragement to diet may be
      counterproductive and that parents need alternative approaches to promote healthy
      patterns of intake and growth among young girls. 

PMID- 24858836
TI  - The effects of extended bedtimes on sleep duration and food desire in overweight
      young adults: a home-based intervention.
AB  - INTRODUCTION:  Sleep curtailment is an endemic behavior in modern society. Well
      controlled laboratory studies have shown that sleep loss in young adults is
      associated with increased desire for high-calorie food and obesity risk. However,
      the relevance of these laboratory findings to real life is uncertain. We
      conducted a 3 week, within-participant, intervention study to assess the effects
      of extended bedtimes on sleep duration and food desire under real life conditions
      in individuals who are at risk for obesity. METHODS:  Ten overweight young adults
      reporting average habitual sleep duration of less than 6.5 h were studied in the
      home environment. Habitual bedtimes for 1-week (baseline) were followed by
      bedtimes extended to 8.5 h for 2-weeks (intervention). Participants were unaware
      of the intervention until after the baseline period. Participants received
      individualized behavioral counseling on sleep hygiene on the first day of the
      intervention period. Sleep duration was recorded by wrist actigraphy throughout
      the study. Participants rated their sleepiness, vigor and desire for various
      foods using visual analog scales at the end of baseline and intervention periods.
      RESULTS:  On average, participants obtained 1.6 h more sleep with extended
      bedtimes (5.6 vs. 7.1; P < 0.001) and reported being less sleepy (P = 0.004) and
      more vigorous (P = 0.034). Additional sleep was associated with a 14% decrease in
      overall appetite (P = 0.030) and a 62% decrease in desire for sweet and salty
      foods (P = 0.017). Desire for fruits, vegetables and protein-rich nutrients was
      not affected by added sleep. CONCLUSIONS:  Sleep duration can be successfully
      increased in real life settings and obtaining adequate sleep is associated with
      less desire for high calorie foods in overweight young adults who habitually
      curtail their sleep.

PMID- 24858838
TI  - Covariance among multiple health risk behaviors in adolescents.
AB  - PURPOSE: In a diverse group of early adolescents, this study explores the co
      occurrence of a broad range of health risk behaviors: alcohol, cigarette, and
      marijuana use; physical inactivity; sedentary computing/gaming; and the
      consumption of low-nutrient energy-dense food. We tested differences in the
      associations of unhealthy behaviors over time, and by gender, race/ethnicity, and
      socioeconomic status. METHODS: Participants were 8360 students from 16 middle
      schools in California (50% female; 52% Hispanic, 17% Asian, 16% White, and 15%
      Black/multiethnic/other). Behaviors were measured with surveys in Spring 2010 and
      Spring 2011. Confirmatory factor analysis was used to assess if an underlying
      factor accounted for the covariance of multiple behaviors, and composite
      reliability methods were used to determine the degree to which behaviors were
      related. RESULTS: The measured behaviors were explained by two moderately
      correlated factors: a 'substance use risk factor' and an 'unhealthy eating and
      sedentary factor'. Physical inactivity did not reflect the latent factors as
      expected. There were few differences in the associations among these behaviors
      over time or by demographic characteristics. CONCLUSIONS: Two distinct, yet
      related groups of health compromising behaviors were identified that could be
      jointly targeted in multiple health behavior change interventions among early
      adolescents of diverse backgrounds.

PMID- 24858837
TI  - Regulation of extracellular ATP in human erythrocytes infected with Plasmodium
      falciparum.
AB  - In human erythrocytes (h-RBCs) various stimuli induce increases in [cAMP] that
      trigger ATP release. The resulting pattern of extracellular ATP accumulation
      (ATPe kinetics) depends on both ATP release and ATPe degradation by ectoATPase
      activity. In this study we evaluated ATPe kinetics from primary cultures of h
      RBCs infected with P. falciparum at various stages of infection (ring,
      trophozoite and schizont stages). A "3V" mixture containing isoproterenol (beta
      adrenergic agonist), forskolin (adenylate kinase activator) and papaverine
      (phosphodiesterase inhibitor) was used to induce cAMP-dependent ATP release. ATPe
      kinetics of r-RBCs (ring-infected RBCs), t-RBCs (trophozoite-infected RBCs) and s
      RBCs (schizont-infected RBCs) showed [ATPe] to peak acutely to a maximum value
      followed by a slower time dependent decrease. In all intraerythrocytic stages,
      values of DeltaATP1 (difference between [ATPe] measured 1 min post-stimulus and
      basal [ATPe]) increased nonlinearly with parasitemia (from 2 to 12.5%). Under 3V
      exposure, t-RBCs at parasitemia 94% (t94-RBCs) showed 3.8-fold higher DeltaATP1
      values than in h-RBCs, indicative of upregulated ATP release. Pre-exposure to
      either 100 uM carbenoxolone, 100 nM mefloquine or 100 uM NPPB reduced DeltaATP1
      to 83-87% for h-RBCs and 63-74% for t94-RBCs. EctoATPase activity, assayed at
      both low nM concentrations (300-900 nM) and 500 uM exogenous ATPe concentrations
      increased approx. 400-fold in t94-RBCs, as compared to h-RBCs, while
      intracellular ATP concentrations of t94-RBCs were 65% that of h-RBCs. In t94
      RBCs, production of nitric oxide (NO) was approx. 7-fold higher than in h-RBCs,
      and was partially inhibited by L-NAME pre-treatment. In media with L-NAME,
      DeltaATP1 values were 2.7-times higher in h-RBCs and 4.2-times higher in t94
      RBCs, than without L-NAME. Results suggest that P. falciparum infection of h-RBCs
      strongly activates ATP release via Pannexin 1 in these cells. Several processes
      partially counteracted ATPe accumulation: an upregulated ATPe degradation, an
      enhanced NO production, and a decreased intracellular ATP concentration. 

PMID- 24858839
TI  - Coadministration of co-trimoxazole with sulfonylureas: hypoglycemia events and
      pattern of use.
AB  - BACKGROUND: Coadministration of co-trimoxazole with sulfonylureas is reported to
      increase the risk of hypoglycemia. METHODS: We identified a cohort of Medicare
      beneficiaries aged 66 years or older who took glyburide or glipizide for diabetes
      from a 5% national sample of Medicare Part D claims data in 2008 (n = 34,239). We
      tracked each participant's claims during 2008-2010 for a co-trimoxazole
      prescription and subsequent emergency room visits for hypoglycemia. Descriptive
      statistics and logistic regression modeling were used to evaluate hypoglycemia
      related emergency room visits after coadministration of co-trimoxazole with
      sulfonylureas and its utilization patterns in older adults with diabetes.
      RESULTS: Sulfonylureas users prescribed co-trimoxazole had a significant higher
      risk of emergency room visits for hypoglycemia, compared with those prescribed
      noninteracting antibiotics (odds ratio = 3.89, 95% confidence interval = 2.29
      6.60 for glipizide and odds ratio = 3.78, 95% confidence interval = 1.81-7.90 for
      glyburide with co-trimoxazole, using amoxicillin as the reference). Co
      trimoxazole was prescribed to 16.9% of those taking glyburide or glipizide during
      2008-2010, varying from 4.0% to 35.9% across U.S. hospital referral regions.
      Patients with polypharmacy and with more prescribers were more likely to receive
      co-trimoxazole. Patients with an identifiable primary care physician had 20%
      lower odds of receiving a co-trimoxazole prescription. Hospital referral regions
      with more PCPs had lower rates of coadministration of the two drugs (r = -.26, p
      < 0.001). CONCLUSIONS: Coadministration of co-trimoxazole with sulfonylureas is
      associated with increased risk of hypoglycemia, compared with noninteracting
      antibiotics. Such coadministration is prevalent among older diabetic patients in
      the United States, especially in patients without an identifiable primary care
      physician.

PMID- 24858840
TI  - A non-autonomous insect piggyBac transposable element is mobile in tobacco.
AB  - The piggyBac transposable element, originally isolated from a virus in an insect
      cell line, is a valuable molecular tool for transgenesis and mutagenesis of
      invertebrates. For heterologous transgenesis in a variety of mammals, transfer of
      the piggyBac transposable element from an ectopic plasmid only requires
      expression of piggyBac transposase. To determine if piggyBac could function in
      dicotyledonous plants, a two-element system was developed in tobacco (Nicotiana
      tabacum) to test for transposable element excision and insertion. The first
      transgenic line constitutively expressed piggyBac transposase, while the second
      transgenic line contained at least two non-autonomous piggyBac transposable
      elements. Progeny from crosses of the two transgenic lines was analyzed for
      piggyBac excision and transposition. Several progeny displayed excision events,
      and all the sequenced excision sites exhibited evidence of the precise excision
      mechanism characteristic of piggyBac transposase. Two unique transposition
      insertion events were identified that each included diagnostic duplication of the
      target site. These data indicate that piggyBac transposase is active in a
      dicotyledonous plant, although at a low frequency. 

PMID- 24858843
TI  - Assessing cerebrovascular autoregulation from critical closing pressure and
      resistance area product during upright posture in aging and hypertension.
AB  - Static cerebral autoregulation (sCA) is believed to be resistant to aging and
      hypertensive pathology. However, methods to characterize autoregulation commonly
      rely on beat-by-beat mean hemodynamic measures and do not consider within-beat
      pulse wave characteristics that are impacted by arterial stiffening. We examined
      the role of critical closing pressure (CrCP) and resistance area product (RAP),
      two measures derived from the pulse wave, across supine lying, sitting, and
      standing postures in young adults, normotensive older adults, and older adults
      with controlled and uncontrolled hypertension (N = 80). Traditional measures of
      sCA, using both intracranial and extracranial methods, indicated similar
      efficiency across all groups, but within-beat measures suggested different
      mechanisms of regulation. At rest, RAP was increased in hypertension compared
      with young adults (P < 0.001), but CrCP was similar. In contrast, the drop in
      CrCP was the primary regulator of change in cerebrovascular resistance upon
      adopting an upright posture. Both CrCP and RAP demonstrated group-by-posture
      interaction effects (P < 0.05), with older hypertensive adults exhibiting a rise
      in RAP that was absent in other groups. The posture-related swings in CrCP and
      RAP were related to changes in both the pulsatile and mean components of arterial
      pressure, independent of age, cardiac output, and carbon dioxide. Group-by
      posture differences in pulse pressure were mediated in part by an attenuated
      heart rate response in older hypertensive adults (P = 0.002). Examination of
      pulsatile measures in young, elderly, and hypertensive adults identified unique
      differences in how cerebral blood flow is regulated in upright posture. 

PMID- 24858842
TI  - Obesity increases inflammation and impairs lymphatic function in a mouse model of
      lymphedema.
AB  - Although obesity is a major clinical risk factor for lymphedema, the mechanisms
      that regulate this effect remain unknown. Recent reports have demonstrated that
      obesity is associated with acquired lymphatic dysfunction. The purpose of this
      study was to determine how obesity-induced lymphatic dysfunction modulates the
      pathological effects of lymphatic injury in a mouse model. We used a diet-induced
      model of obesity in adult male C57BL/6J mice in which experimental animals were
      fed a high-fat diet and control animals were fed a normal chow diet for 8-10 wk.
      We then surgically ablated the superficial and deep lymphatics of the midportion
      of the tail. Six weeks postoperatively, we analyzed changes in lymphatic
      function, adipose deposition, inflammation, and fibrosis. We also compared
      responses to acute inflammatory stimuli in obese and lean mice. Compared with
      lean control mice, obese mice had baseline decreased lymphatic function.
      Lymphedema in obese mice further impaired lymphatic function and resulted in
      increased subcutaneous adipose deposition, increased CD45(+) and CD4(+) cell
      inflammation (P < 0.01), and increased fibrosis, but caused no change in the
      number of lymphatic vessels. Interestingly, obese mice had a significantly
      increased acute inflammatory reaction to croton oil application. In conclusion,
      obese mice have impaired lymphatic function at baseline that is amplified by
      lymphatic injury. This effect is associated with increased chronic inflammation,
      fibrosis, and adipose deposition. These findings suggest that obese patients are
      at higher risk for lymphedema due to impaired baseline lymphatic clearance and an
      increased propensity for inflammation in response to injury. 

PMID- 24858841
TI  - Structural synaptic plasticity has high memory capacity and can explain graded
      amnesia, catastrophic forgetting, and the spacing effect.
AB  - Although already William James and, more explicitly, Donald Hebb's theory of cell
      assemblies have suggested that activity-dependent rewiring of neuronal networks
      is the substrate of learning and memory, over the last six decades most
      theoretical work on memory has focused on plasticity of existing synapses in
      prewired networks. Research in the last decade has emphasized that structural
      modification of synaptic connectivity is common in the adult brain and tightly
      correlated with learning and memory. Here we present a parsimonious computational
      model for learning by structural plasticity. The basic modeling units are
      "potential synapses" defined as locations in the network where synapses can
      potentially grow to connect two neurons. This model generalizes well-known
      previous models for associative learning based on weight plasticity. Therefore,
      existing theory can be applied to analyze how many memories and how much
      information structural plasticity can store in a synapse. Surprisingly, we find
      that structural plasticity largely outperforms weight plasticity and can achieve
      a much higher storage capacity per synapse. The effect of structural plasticity
      on the structure of sparsely connected networks is quite intuitive: Structural
      plasticity increases the "effectual network connectivity", that is, the network
      wiring that specifically supports storage and recall of the memories. Further,
      this model of structural plasticity produces gradients of effectual connectivity
      in the course of learning, thereby explaining various cognitive phenomena
      including graded amnesia, catastrophic forgetting, and the spacing effect. 

PMID- 24858845
TI  - Physiological interdependence of the cardiovascular and postural control systems
      under orthostatic stress.
AB  - The cardiovascular system has been observed to respond to changes in human
      posture and the environment. On the same lines, frequent fallers have been
      observed to suffer from cardiovascular deficits. The present article aims to
      demonstrate the existence of interactions between the cardiovascular and postural
      control systems. The behavior of the two systems under orthostatic challenge was
      studied through novel adaptations of signal processing techniques. To this
      effect, the interactions between the two systems were assessed with two metrics,
      coherence and phase lock value, based on the wavelet transform. Measurements from
      the cardiovascular system (blood pressure), lower limb muscles (surface
      electromyography), and postural sway (center of pressure) were acquired from
      young healthy adults (n = 28, men = 12, age = 20-28 yr) during quiet stance. The
      continuous wavelet transform was applied to decompose the representative signals
      on a time-scale basis in a frequency region of 0.01 to 0.1 Hz. Their linear
      coupling was quantified through a coherence metric, and the synchrony was
      characterized via the phase information. The outcomes of this study present
      evidence that the cardiovascular and postural control systems work together to
      maintain homeostasis under orthostatic challenge. The inferences open a new
      direction of study for effects under abnormalities and extreme environmental
      conditions. 

PMID- 24858844
TI  - Estrogen regulation of the brain renin-angiotensin system in protection against
      angiotensin II-induced sensitization of hypertension.
AB  - This study investigated sex differences in the sensitization of angiotensin (ANG)
      II-induced hypertension and the role of central estrogen and ANG-(1-7) in this
      process. Male and female rats were implanted for telemetered blood pressure (BP)
      recording. A subcutaneous subpressor dose of ANG II was given alone or
      concurrently with intracerebroventricular estrogen, ANG-(1-7), an ANG-(1-7)
      receptor antagonist A-779 or vehicle for 1 wk (induction). After a 1-wk rest
      (delay), a pressor dose of ANG II was given for 2 wk (expression). In males and
      ovariectomized females, subpressor ANG II had no sustained effect on BP during
      induction, but produced an enhanced hypertensive response to the subsequent
      pressor dose of ANG II during expression. Central administration of estrogen or
      ANG-(1-7) during induction blocked ANG II-induced sensitization. In intact
      females, subpressor ANG II treatment produced a decrease in BP during induction
      and delay, and subsequent pressor ANG II treatment given during expression
      produced only a slight but significant increase in BP. However, central blockade
      of ANG-(1-7) by intracerebroventricular infusion of A-779 during induction
      restored the decreased BP observed in females during induction and enhanced the
      pressor response to the ANG II treatment during expression. RT-PCR analyses
      indicated that estrogen given during induction upregulated mRNA expression of the
      renin-angiotensin system (RAS) antihypertensive components, whereas both central
      estrogen and ANG-(1-7) downregulated mRNA expression of RAS hypertensive
      components in the lamina terminalis. The results indicate that females are
      protected from ANG II-induced sensitization through central estrogen and its
      regulation of brain RAS. 

PMID- 24858846
TI  - A method for noninvasive longitudinal measurements of [Ca2+] in arterioles of
      hypertensive optical biosensor mice.
AB  - We used two-photon (2-p) Forster resonance energy transfer (FRET) microscopy to
      provide serial, noninvasive measurements of [Ca(2+)] in arterioles of living
      "biosensor" mice. These express a genetically encoded Ca(2+) indicator (GECI),
      either FRET-based exMLCK or intensity-based GCaMP2. The FRET ratios, Rmin and
      Rmax, required for in vivo Ca(2+) calibration of exMLCK were obtained in isolated
      arteries. For in vivo experiments, mice were anesthetized (1.5% isoflurane), and
      arterioles within a depilated ear were visualized through the intact skin (i.e.,
      noninvasively), by 2-p excitation of exMLCK (at 820 nm) or GCaMP2 (at 920 nm).
      Spontaneous or agonist-evoked [Ca(2+)] transients in arteriolar smooth muscle
      cells were imaged (at 2 Hz) with both exMLCK and GCaMP2. To examine changes in
      arteriolar [Ca(2+)] that might accompany hypertension, five exMLCK mice were
      implanted with telemetric blood pressure transducers and osmotic minipumps
      containing ANG II (350 ng.kg(-1).min(-1)) and fed a high (6%)-salt diet for 9
      days. [Ca(2+)] was measured every other day in five smooth muscle cells of two to
      three arterioles in each animal. Prior to ANG II/salt, [Ca(2+)] was 246 +/- 42
      nM. [Ca(2+)] increased transiently to 599 nM on day 2 after beginning ANG
      II/salt, then remained elevated at 331 +/- 42 nM for 4 more days, before
      returning to 265 +/- 47 nM 6 days after removal of ANG II/salt. In summary, two
      photon excitation of exMLCK and GCaMP2 provides a method for noninvasive,
      longitudinal quantification of [Ca(2+)] dynamics and vascular structure in
      individual arterioles of a particular animal over an extended period of time, a
      capability that should enhance future studies of hypertension and vascular
      function. 

PMID- 24858847
TI  - An optimized method for the estimation of the respiratory rate from
      electrocardiographic signals: implications for estimating minute ventilation.
AB  - It is well-known that respiratory activity influences electrocardiographic (ECG)
      morphology. In this article we present a new algorithm for the extraction of
      respiratory rate from either intracardiac or body surface electrograms. The
      algorithm optimizes selection of ECG leads for respiratory analysis, as validated
      in a swine model. The algorithm estimates the respiratory rate from any two ECG
      leads by finding the power spectral peak of the derived ratio of the estimated
      root-mean-squared amplitude of the QRS complexes on a beat-by-beat basis across a
      32-beat window and automatically selects the lead combination with the highest
      power spectral signal-to-noise ratio. In 12 mechanically ventilated swine, we
      collected intracardiac electrograms from catheters in the right ventricle,
      coronary sinus, left ventricle, and epicardial surface, as well as body surface
      electrograms, while the ventilation rate was varied between 7 and 13 breaths/min
      at tidal volumes of 500 and 750 ml. We found excellent agreement between the
      estimated and true respiratory rate for right ventricular (R(2) = 0.97), coronary
      sinus (R(2) = 0.96), left ventricular (R(2) = 0.96), and epicardial (R(2) = 0.97)
      intracardiac leads referenced to surface lead ECGII. When applied to intracardiac
      right ventricular-coronary sinus bipolar leads, the algorithm exhibited an
      accuracy of 99.1% (R(2) = 0.97). When applied to 12-lead body surface ECGs
      collected in 4 swine, the algorithm exhibited an accuracy of 100% (R(2) = 0.93).
      In conclusion, the proposed algorithm provides an accurate estimation of the
      respiratory rate using either intracardiac or body surface signals without the
      need for additional hardware. 

PMID- 24858849
TI  - MicroRNAs associated with ischemia-reperfusion injury and cardioprotection by
      ischemic pre- and postconditioning: protectomiRs.
AB  - We aimed to characterize early changes in microRNA expression in acute
      cardioprotection by ischemic pre- and postconditioning in rat hearts. Hearts
      isolated from male Wistar rats were subjected to 1) time-matched nonischemic
      perfusion, 2) ischemia-reperfusion (30 min of coronary occlusion and 120 min of
      reperfusion), 3) preconditioning (3 * 5 min of coronary occlusion) followed by
      ischemia-reperfusion, or 4) ischemia-reperfusion with postconditioning (6 * 10 s
      of global ischemia-reperfusion at the onset of reperfusion). Infarct size was
      significantly reduced by both interventions. Of 350 different microRNAs assessed
      by microarray analysis, 147-160 microRNAs showed detectable expression levels.
      Compared with microRNA alterations induced by ischemia-reperfusion versus time
      matched nonischemic controls, five microRNAs were significantly affected by both
      pre- and postconditioning (microRNA-125b*, microRNA-139-3p, microRNA-320,
      microRNA-532-3p, and microRNA-188), four microRNAs were significantly affected by
      preconditioning (microRNA-487b, microRNA-139-5p, microRNA-192, and microRNA-212),
      and nine microRNAs were significantly affected by postconditioning (microRNA-1,
      microRNA let-7i, microRNA let-7e, microRNA let-7b, microRNA-181a, microRNA-208,
      microRNA-328, microRNA-335, and microRNA-503). Expression of randomly selected
      microRNAs was validated by quantitative real-time PCR. By a systematic comparison
      of the direction of microRNA expression changes in all groups, we identified
      microRNAs, specific mimics, or antagomiRs that may have pre- and postconditioning
      like cardioprotective effects (protectomiRs). Transfection of selected
      protectomiRs (mimics of microRNA-139-5p, microRNA-125b*, microRNA let-7b, and
      inhibitor of microRNA-487b) into cardiac myocytes subjected to simulated ischemia
      reperfusion showed a significant cytoprotective effect. This is the first
      demonstration that the ischemia-reperfusion-induced microRNA expression profile
      is significantly influenced by both pre- and postconditioning, which shows the
      involvement of microRNAs in cardioprotective signaling. Moreover, by analysis of
      microRNA expression patterns in cardioprotection by pre- and postconditioning,
      specific protectomiRs can be revealed as potential therapeutic tools for the
      treatment of ischemia-reperfusion injury. 

PMID- 24858848
TI  - HDAC6 contributes to pathological responses of heart and skeletal muscle to
      chronic angiotensin-II signaling.
AB  - Little is known about the function of the cytoplasmic histone deacetylase HDAC6
      in striated muscle. Here, we addressed the role of HDAC6 in cardiac and skeletal
      muscle remodeling induced by the peptide hormone angiotensin II (ANG II), which
      plays a central role in blood pressure control, heart failure, and associated
      skeletal muscle wasting. Comparable with wild-type (WT) mice, HDAC6 null mice
      developed cardiac hypertrophy and fibrosis in response to ANG II. However,
      whereas WT mice developed systolic dysfunction upon treatment with ANG II,
      cardiac function was maintained in HDAC6 null mice treated with ANG II for up to
      8 wk. The cardioprotective effect of HDAC6 deletion was mimicked in WT mice
      treated with the small molecule HDAC6 inhibitor tubastatin A. HDAC6 null mice
      also exhibited improved left ventricular function in the setting of pressure
      overload mediated by transverse aortic constriction. HDAC6 inhibition appeared to
      preserve systolic function, in part, by enhancing cooperativity of myofibrillar
      force generation. Finally, we show that HDAC6 null mice are resistant to skeletal
      muscle wasting mediated by chronic ANG-II signaling. These findings define novel
      roles for HDAC6 in striated muscle and suggest potential for HDAC6-selective
      inhibitors for the treatment of cardiac dysfunction and muscle wasting in
      patients with heart failure. 

PMID- 24858850
TI  - More in vivo experimentation is needed in cardiovascular physiology.

PMID- 24858851
TI  - Ca2+/calmodulin-dependent protein kinase II increases the susceptibility to the
      arrhythmogenic action potential alternans in spontaneously hypertensive rats.
AB  - Action potential duration alternans (APD-ALT), defined as long-short-long
      repetitive pattern of APD, potentially leads to lethal ventricular arrhythmia.
      However, the mechanisms of APD-ALT in the arrhythmogenesis of cardiac hypertrophy
      remain undetermined. Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is
      known to modulate the function of cardiac sarcoplasmic reticulum and play an
      important role in Ca(2+) cycling. We thus aimed to determine the role of CaMKII
      in the increased susceptibility to APD-ALT and arrhythmogenesis in the
      hypertrophied heart. APD was measured by high-resolution optical mapping in left
      ventricular (LV) anterior wall from normotensive Wistar-Kyoto (WKY; n = 10) and
      spontaneously hypertensive rats (SHR; n = 10) during rapid ventricular pacing.
      APD-ALT was evoked at significantly lower pacing rate in SHR compared with WKY
      (382 +/- 43 vs. 465 +/- 45 beats/min, P < 0.01). These changes in APD-ALT in SHR
      were completely reversed by KN-93 (1 MUmol/l; n = 5), an inhibitor of CaMKII, but
      not its inactive analog, KN-92 (1 MUmol/l; n = 5). The magnitude of APD-ALT was
      also significantly greater in SHR than WKY and was completely normalized by KN
      93. Ventricular fibrillation (VF) was induced by rapid pacing more frequently in
      SHR than in WKY (60 vs. 10%; P < 0.05), which was also abolished by KN-93 (0%, P
      < 0.05). Western blot analyses indicated that the CaMKII autophosphorylation at
      Thr287 was significantly increased in SHR compared with WKY. The increased
      susceptibility to APD-ALT and VF during rapid pacing in hypertrophied heart was
      prevented by KN-93. CaMKII could be an important mechanism of arrhythmogenesis in
      cardiac hypertrophy. 

PMID- 24858852
TI  - Sympathetic predominance is associated with impaired endothelial progenitor cells
      and tunneling nanotubes in controlled-hypertensive patients.
AB  - Early endothelial progenitor cells (early EPC) and late EPC are involved in
      endothelial repair and can rescue damaged endothelial cells by transferring
      organelles through tunneling nanotubes (TNT). In rodents, EPC mobilization from
      the bone marrow depends on sympathetic nervous system activity. Indirect evidence
      suggests a relation between autonomic derangements and human EPC mobilization. We
      aimed at testing whether hypertension-related autonomic imbalances are associated
      with EPC impairment. Thirty controlled-essential hypertensive patients [systolic
      blood pressure/diastolic blood pressure = 130(120-137)/85(61-88) mmHg; 81.8%
      male] and 20 healthy normotensive subjects [114(107-119)/75(64-79) mmHg; 80%
      male] were studied. Mononuclear cells were cultured on fibronectin- and collagen
      coated dishes for early EPC and late EPC, respectively. Low (LF)- and high (HF)
      frequency components of short-term heart rate variability were analyzed during a
      5-min rest, an expiration/inspiration maneuver, and a Stroop color-word test.
      Modulations of cardiac sympathetic and parasympathetic activities were evaluated
      by LF/HF (%) and HF power (ms(2)), respectively. In controlled-hypertensive
      patients, the numbers of early EPC, early EPC that emitted TNT, late EPC, and
      late EPC that emitted TNT were 41, 77, 50, and 88% lower than in normotensive
      subjects (P < 0.008), respectively. In controlled-hypertensive patients, late EPC
      number was positively associated with cardiac parasympathetic reserve during the
      expiration/inspiration maneuver (rho = 0.45, P = 0.031) and early EPC with
      brachial flow-mediated dilation (rho = 0.655; P = 0.049); also, late TNT number
      was inversely related to cardiac sympathetic response during the stress test (rho
      = -0.426, P = 0.045). EPC exposure to epinephrine or norepinephrine showed
      negative dose-response relationships on cell adhesion to fibronectin and
      collagen; both catecholamines stimulated early EPC growth, but epinephrine
      inhibited late EPC growth. In controlled-hypertensive patients, sympathetic
      overactivity/parasympathetic underactivity were negatively associated with EPC,
      suggesting that reducing sympathetic/increasing parasympathetic activation might
      favor endothelial repair. 

PMID- 24858853
TI  - Diverse forms of pulmonary hypertension remodel the arterial tree to a high shear
      phenotype.
AB  - Pulmonary hypertension (PH) is associated with progressive changes in arterial
      network complexity. An allometric model is derived that integrates diameter
      branching complexity between pulmonary arterioles of generation n and the main
      pulmonary artery (MPA) via a power-law exponent (X) in dn = dMPA2(-n/X) and the
      arterial area ratio beta = 2(1-2/X). Our hypothesis is that diverse forms of PH
      demonstrate early decrements in X independent of etiology and pathogenesis, which
      alters the arteriolar shear stress load from a low-shear stress (X > 2, beta > 1)
      to a high-shear stress phenotype (X < 2, beta < 1). Model assessment was
      accomplished by comparing theoretical predictions to retrospective morphometric
      and hemodynamic measurements made available from a total of 221 PH-free and PH
      subjects diagnosed with diverse forms (World Health Organization; WHO groups I
      IV) of PH: mitral stenosis, congenital heart disease, chronic obstructive
      pulmonary lung disease, chronic thromboembolism, idiopathic pulmonary arterial
      hypertension (IPAH), familial (FPAH), collagen vascular disease, and
      methamphetamine exposure. X was calculated from pulmonary artery pressure (PPA),
      cardiac output (Q) and body weight (M), utilizing an allometric power-law
      prediction of X relative to a PH-free state. Comparisons of X between PAH-free
      and PAH subjects indicates a characteristic reduction in area that elevates
      arteriolar shear stress, which may contribute to mechanisms of endothelial
      dysfunction and injury before clinically defined thresholds of pulmonary vascular
      resistance and PH. We conclude that the evaluation of X may be of use in
      identifying reversible and irreversible phases of PH in the early course of the
      disease process. 

PMID- 24858854
TI  - Heparan sulfate side chains have a critical role in the inhibitory effects of
      perlecan on vascular smooth muscle cell response to arterial injury.
AB  - Perlecan is a proteoglycan composed of a 470-kDa core protein linked to three
      heparan sulfate (HS) glycosaminoglycan chains. The intact proteoglycan inhibits
      the smooth muscle cell (SMC) response to vascular injury. Hspg2(Delta3/Delta3)
      (MDelta3/Delta3) mice produce a mutant perlecan lacking the HS side chains. The
      objective of this study was to determine differences between these two types of
      perlecan in modifying SMC activities to the arterial injury response, in order to
      define the specific role of the HS side chains. In vitro proliferative and
      migratory activities were compared in SMC isolated from MDelta3/Delta3 and wild
      type mice. Proliferation of MDelta3/Delta3 SMC was 1.5* greater than in wild type
      (P < 0.001), increased by addition of growth factors, and showed a 42% greater
      migratory response than wild-type cells to PDGF-BB (P < 0.001). In MDelta3/Delta3
      SMC adhesion to fibronectin, and collagen types I and IV was significantly
      greater than wild type. Addition of DRL-12582, an inducer of perlecan expression,
      decreased proliferation and migratory response to PDGF-BB stimulation in wild
      type SMC compared with MDelta3/Delta3. In an in vivo carotid artery wire injury
      model, the medial thickness, medial area/lumen ratio, and macrophage infiltration
      were significantly increased in the MDelta3/Delta3 mice, indicating a prominent
      role of the HS side chain in limiting vascular injury response. Mutant perlecan
      that lacks HS side chains had a marked reduction in the inhibition of in vitro
      SMC function and the in vivo arterial response to injury, indicating the critical
      role of HS side chains in perlecan function in the vessel wall. 

PMID- 24858855
TI  - Dynamic phosphorylation of VE-cadherin Y685 throughout mouse estrous cycle in
      ovary and uterus.
AB  - We previously reported that vascular endothelial growth factor induced vascular
      endothelial (VE)-cadherin tyrosine phosphorylation at Y685 in a Src-dependent
      manner in vitro. Here, we studied the occurrence of Y685 phosphorylation in vivo
      in the female reproductive tract because it is a unique model of physiological
      vascular remodeling dependent on vascular endothelial growth factor. We first
      developed and characterized an anti-phospho-specific antibody against the site
      Y685 of VE-cadherin to monitor VE-cadherin phosphorylation along the four phases
      of mouse estrous cycle, termed proestrus, estrus, metestrus, and diestrus. A
      dynamic profile of tyrosine phosphorylated proteins was observed in both uterus
      and ovary throughout mouse estrous cycle, including kinase Src, which was found
      highly active at the estrus phase. The extent of tyrosine phosphorylated VE
      cadherin was low at proestrus but strongly increased at estrus and returned to
      baseline at metestrus and diestrus, suggesting a potent hormonal regulation of
      this specific process. Indeed, C57Bl/6 female mice treatment with pregnant mare
      serum gonadotropin and human chorionic gonadotropin confirmed a significant
      increase in phosphoY685-VE-cadherin compared with that in untreated mice. These
      results demonstrate that VE-cadherin tyrosine phosphorylation at Y685 is a
      physiological and hormonally regulated process in female reproductive organs. In
      addition, this process was concomitant with the early steps of vascular
      remodeling taking place at estrus stage, suggesting that phosphoY685-VE-cadherin
      is a biomarker of endothelial cell activation in vivo. 

PMID- 24858856
TI  - VE-cadherin Y685F knock-in mouse is sensitive to vascular permeability in
      recurrent angiogenic organs.
AB  - Covalent modifications such as tyrosine phosphorylation are associated with the
      breakdown of endothelial cell junctions and increased vascular permeability. We
      previously showed that vascular endothelial (VE)-cadherin was tyrosine
      phosphorylated in vivo in the mouse reproductive tract and that Y685 was a target
      site for Src in response to vascular endothelial growth factor in vitro. In the
      present study, we aimed to understand the implication of VE-cadherin
      phosphorylation at site Y685 in cyclic angiogenic organs. To achieve this aim, we
      generated a knock-in mouse carrying a tyrosine-to-phenylalanine point mutation of
      VE-cadherin Y685 (VE-Y685F). Although homozygous VE-Y685F mice were viable and
      fertile, the nulliparous knock-in female mice exhibited enlarged uteri with
      edema. This phenotype was observed in 30% of females between 4 to 14 mo old.
      Histological examination of longitudinal sections of the VE-Y685F uterus showed
      an extensive disorganization of myometrium and endometrium with highly edematous
      uterine glands, numerous areas with sparse cells, and increased accumulation of
      collagen fibers around blood vessels, indicating a fibrotic state. Analysis of
      cross section of ovaries showed the appearance of spontaneous cysts, which
      suggested increased vascular hyperpermeability. Electron microscopy analysis of
      capillaries in the ovary showed a slight but significant increase in the gap size
      between two adjacent endothelial cell membranes in the junctions of VE-Y685F mice
      (wild-type, 11.5 +/- 0.3, n = 78; and VE-Y685F, 12.48 +/- 0.3, n = 65; P =
      0.045), as well as collagen fiber accumulation around capillaries. Miles assay
      revealed that either basal or vascular endothelial growth factor-stimulated
      permeability in the skin was increased in VE-Y685F mice. Since edema and fibrotic
      appearance have been identified as hallmarks of initial increased vascular
      permeability, we conclude that the site Y685 in VE-cadherin is involved in the
      physiological regulation of capillary permeability. Furthermore, this knock-in
      mouse model is of potential interest for further studies of diseases that are
      associated with abnormal vascular permeability. 

PMID- 24858857
TI  - Decreased basal ganglia activation in subjects with chronic fatigue syndrome:
      association with symptoms of fatigue.
AB  - Reduced basal ganglia function has been associated with fatigue in neurologic
      disorders, as well as in patients exposed to chronic immune stimulation. Patients
      with chronic fatigue syndrome (CFS) have been shown to exhibit symptoms
      suggestive of decreased basal ganglia function including psychomotor slowing,
      which in turn was correlated with fatigue. In addition, CFS patients have been
      found to exhibit increased markers of immune activation. In order to directly
      test the hypothesis of decreased basal ganglia function in CFS, we used
      functional magnetic resonance imaging to examine neural activation in the basal
      ganglia to a reward-processing (monetary gambling) task in a community sample of
      59 male and female subjects, including 18 patients diagnosed with CFS according
      to 1994 CDC criteria and 41 non-fatigued healthy controls. For each subject, the
      average effect of winning vs. losing during the gambling task in regions of
      interest (ROI) corresponding to the caudate nucleus, putamen, and globus pallidus
      was extracted for group comparisons and correlational analyses. Compared to non
      fatigued controls, patients with CFS exhibited significantly decreased activation
      in the right caudate (p = 0.01) and right globus pallidus (p = 0.02). Decreased
      activation in the right globus pallidus was significantly correlated with
      increased mental fatigue (r2 = 0.49, p = 0.001), general fatigue (r2 = 0.34, p =
      0.01) and reduced activity (r2 = 0.29, p = 0.02) as measured by the
      Multidimensional Fatigue Inventory. No such relationships were found in control
      subjects. These data suggest that symptoms of fatigue in CFS subjects were
      associated with reduced responsivity of the basal ganglia, possibly involving the
      disruption of projections from the globus pallidus to thalamic and cortical
      networks. 

PMID- 24858858
TI  - Early induction of oxidative stress in a mouse model of Alzheimer's disease with
      heme oxygenase activity.
AB  - Evidence suggests that brain tissues of patients with Alzheimer's disease (AD)
      are easily attacked by oxidative stress, and numerous studies indicate that heme
      oxygenase (HO) is a major cell adaptive responder to stress. However, whether HO
      1 and HO-2 play different roles in this process has not yet been studied. In the
      present study, it was shown in an AD model that HO-1 and HO-2 have different
      roles in the early stages of AD. Learning and memory ability was tested in
      APPswe/PS1DeltaE9 (APP/PS1) transgenic and wild-type mice using the Morris water
      maze. beta-amyloid plaques were measured using immunofluorescence staining.
      Changes in reactive oxygen species (ROS) levels in the hippocampi were measured
      using a fluorescence technique. The results indicated that the escape latency,
      amyloid plaque deposition and ROS production increased in the hippocampi of
      APP/PS1 transgenic mice compared with wild-type mice. Furthermore, using double
      immunofluorescence staining and western blot analysis, it was found that the
      expression of HO-1 and HO-2 increased in the hippocampi of APP/PS1 mice and,
      notably, HO-2 was also found to be overexpressed in astrocytes. Little difference
      was observed in the plasma HO-1 concentrations between the two groups, while the
      plasma HO-2 concentration of the APP/PS1 mice was lower than that of the wild
      type mice, shown by ELISA. In conclusion, HO-2 overexpression is an early event
      and plays a more critical role in the progression of AD. 

PMID- 24858859
TI  - Glycine is a nutritionally essential amino acid for maximal growth of milk-fed
      young pigs.
AB  - Analysis of amino acids in milk protein reveals a relatively low content of
      glycine. This study was conducted with young pigs to test the hypothesis that
      milk-fed neonates require dietary glycine supplementation for maximal growth.
      Fourteen-day-old piglets were allotted randomly into one of four treatments (15
      piglets/treatment), representing supplementation with 0, 0.5, 1 or 2% glycine
      (dry matter basis) to a liquid milk replacer. Food was provided to piglets every
      8 h (3 times/day) for 2 weeks. Milk intake (32.0-32.5 g dry matter/kg body weight
      per day) did not differ between control and glycine-supplemented piglets.
      Compared with control piglets, dietary supplementation with 0.5, 1 and 2% glycine
      increased (P < 0.05) plasma concentrations of glycine and serine, daily weight
      gain, and body weight without affecting body composition, while reducing plasma
      concentrations of ammonia, urea, and glutamine, in a dose-dependent manner.
      Dietary supplementation with 0.5, 1 and 2% glycine enhanced (P < 0.05) small
      intestinal villus height, glycine transport (measured using Ussing chambers),
      mRNA levels for GLYT1, and anti-oxidative capacity (indicated by increased
      concentrations of reduced glutathione and a decreased ratio of oxidized
      glutathione to reduced glutathione). These novel results indicate, for the first
      time, that glycine is a nutritionally essential amino acid for maximal protein
      accretion in milk-fed piglets. The findings not only enhance understanding of
      protein nutrition, but also have important implications for designing improved
      formulas to feed human infants, particularly low birth weight and preterm
      infants.

PMID- 24858860
TI  - Disparities in contraceptive care.

PMID- 24858861
TI  - Cultural sensitivity and health education: essential components to the success of
      the early detection cancer screening program for Latinas at MedStar Georgetown
      University Hospital.
AB  - Over 13 years, the Celebremos la Vida (CLV) program has offered free breast
      examinations, mammograms, and cervical cancer screenings to uninsured Latinas
      residing in the Northern Virginia suburbs of Washington, D.C. The CLV program
      aims to educate participants on the importance of breast self-examination and
      regular cancer screening for the early detection of breast and cervical cancer.

PMID- 24858862
TI  - Eliminating health disparities through culturally and linguistically centered
      integrated health care: consensus statements, recommendations, and key strategies
      from the field.
AB  - This report is the outcome of an expert consensus meeting sponsored by the United
      States Deparment of Health and Human Services Office of Minority Health, which
      was convened to formulate consensus statements, provide recommendations and
      identify key strategies from practice for implementing integrated health and
      behavioral health care intended to improve health status for underserved
      populations.

PMID- 24858864
TI  - Factors associated with perceived patient-provider communication quality among
      Puerto Ricans.
AB  - Patient-provider communication is an important factor influencing patients'
      health outcomes. This study examined the relationship between patient-provider
      communication quality and sociodemographic, health care access, trusted
      information sources, and health status variables. Data were from a representative
      sample of 450 Puerto Rican adults who participated in the Health Information
      National Trends Survey. A composite score rating perceived patient-provider
      communication quality was created from five items (Cronbach's alpha = 0.87). A
      multivariate linear regression analysis was conducted. Patient-provider
      communication ratings were lower among the unemployed (p = 0.049), those who do
      not trust a lot in the information provided by their providers (p = 0.003), and
      respondents with higher depressive symptoms scores (p = 0.036). Perceived patient
      provider communication quality, however, was higher among respondents who visited
      their providers five or more times in the last year (p = 0.023). Understanding
      patient perceptions of provider communication may serve to develop system-level
      interventions aimed at eliminating communication disparities and improving
      patients' health outcomes. 

PMID- 24858863
TI  - Low socioeconomic status is associated with increased risk for hypoglycemia in
      diabetes patients: the Diabetes Study of Northern California (DISTANCE).
AB  - BACKGROUND: Social risk factors for hypoglycemia are not well understood.
      METHODS: Cross-sectional analysis from the DISTANCE study, a multi-language,
      ethnically-stratified random sample of adults in the Kaiser Permanente Northern
      California diabetes registry, conducted in 2005-2006 (response rate 62%).
      Exposures were income and educational attainment; outcome was patient report of
      severe hypoglycemia. To test the association, we used multivariable logistic
      regression to adjust for demographic and clinical factors. RESULTS: 14,357
      patients were included. Reports of severe hypoglycemia were common (11%), and
      higher in low-income vs. high-income (16% vs. 8.8) and low-education vs. high
      education (11.9% vs. 8.9%) groups. In multivariable analysis, incomes of less
      than $15,000 (OR 1.51 95%CI 1.19-1.91), $15,000-$24,999 (OR 1.57 95%CI 1.27
      1.94), and high school or less education (OR 1.42, 95% CI 1.24-1.63) were
      associated with increased hypoglycemia, similar to insulin use (OR 1.44 95%CI
      1.19-1.74). CONCLUSIONS: Low income and educational attainment are important risk
      factors for hypoglycemia.

PMID- 24858867
TI  - Perceived social stress, pregnancy-related anxiety, depression and subjective
      social status among pregnant Mexican and Mexican American women in south Texas.
AB  - PURPOSE: The purpose of this study was to determine differences in subjective
      social status, perceived social stress, depressive symptoms, and pregnancy
      related anxiety between pregnant Mexican American and Mexican immigrant women.
      METHODS: Three hundred pregnant Mexican immigrant and Mexican American women in
      South Texas were surveyed for pregnancy-related anxiety, perceived social stress,
      depressive symptoms, and subjective social status. RESULTS: Pregnant Mexican
      immigrant women had higher levels of pregnancy-related anxiety and lower levels
      of depression and perceived social stress than pregnant Mexican American women.
      Change in these variables among Mexican immigrant women was relatively linear as
      time of residence in the United States increased. Mexican immigrant and Mexican
      American women had significantly different correlations between subjective social
      status, self-esteem and perceived social stress. CONCLUSIONS: Results indicate
      that subjective social status is an important psychosocial variable among
      pregnant Hispanic women. Results contribute to ongoing efforts to provide
      culturally responsive prenatal psychosocial support services.

PMID- 24858865
TI  - Religious beliefs and cancer screening behaviors among Catholic Latinos:
      implications for faith-based interventions.
AB  - Although most U.S. Latinos identify as Catholic, few studies have focused on the
      influence of this religious tradition on health beliefs among this population.
      This study explores the role of Catholic religious teachings, practices, and
      ministry on cancer screening knowledge, attitudes, and behaviors among Latinos.
      Eight focus groups were conducted with 67 Catholic Latino parishioners in
      Massachusetts. Qualitative analysis provided evidence of strong reliance on
      faith, God, and parish leaders for health concerns. Parishes were described as
      vital sources of health and social support, playing a central role in the
      community's health. Participants emphasized that their religious beliefs promote
      positive health behaviors and health care utilization, including the use of
      cancer screening services. In addition, they expressed willingness to participate
      in cancer education programs located at their parishes and provided practical
      recommendations for implementing health programs in parishes. Implications for
      culturally appropriate health communication and faith-based interventions are
      discussed. 

PMID- 24858866
TI  - Community health center provider and staff's Spanish language ability and
      cultural awareness.
AB  - Many community health center providers and staff care for Latinos with diabetes,
      but their Spanish language ability and awareness of Latino culture are unknown.
      We surveyed 512 Midwestern health center providers and staff who managed Latino
      patients with diabetes. Few respondents had high Spanish language (13%) or
      cultural awareness scores (22%). Of respondents who self-reported 76-100% of
      their patients were Latino, 48% had moderate/low Spanish language and 49% had
      moderate/low cultural competency scores. Among these respondents, 3% lacked
      access to interpreters and 27% had neither received cultural competency training
      nor had access to training. Among all respondents, Spanish skills and Latino
      cultural awareness were low. Respondents who saw a significant number of Latinos
      had good access to interpretation services but not cultural competency training.
      Improved Spanish-language skills and increased access to cultural competency
      training and Latino cultural knowledge are needed to provide linguistically and
      culturally tailored care to Latino patients. 

PMID- 24858868
TI  - Does a wife's education influence spousal agreement on approval of family
      planning?: Random-effects Modeling using data from two West African Countries.
AB  - Spousal approval of family planning is critical for contraceptive use. Both
      contraceptive use rates and women's education are low in many West-African
      countries and this study examines the role of wives' education in spousal
      agreement on approval of family planning in two sub-Saharan West African
      countries. We used couples' data from Demographic Health Surveys in Senegal and
      in Niger, conducted in 2005 and 2006, respectively. Multiple logistic regression
      results using multilevel modeling show that the odds of spousal agreement on
      approval of family planning were slightly over three times [OR: 3.16; 95% CI:
      1.32 to 7.57] in Senegal and were about three times [OR: 3.07; 95% CI: 1.64 to
      5.76] in Niger higher for women with more than primary education. Findings
      suggest that improvement in women's education could lead to spousal agreement on
      approval of family planning, which may lead to use of family planning in sub
      Saharan African countries. 

PMID- 24858869
TI  - Ethnic variation in access to health care of Asian Americans who are not U.S.
      citizens: Chinese, Korean, and Vietnamese ethnic groups.
AB  - Using the 2009 California Health Interview Survey, this study examined ethnic
      variation in the predictors of having a usual source of health care among Asian
      Americans who are non-U.S. citizens. Chinese residents reported the highest
      probability of having a usual source of health care (78.0%), followed by
      Vietnamese (59.8%) and Korean residents (45.2%), and the differences were
      statistically significant (chi2 = 11.65, p < .01). Poverty status was the only
      significant predictor for Korean residents and insurance status was the only
      significant predictor for Vietnamese residents. By contrast, both poverty and
      insurance status predicted which Chinese residents had a usual source of care. To
      enhance health care access for vulnerable subgroups of non-U.S. citizens, health
      care professionals must be aware that there are cultural differences in the
      predictors of having a usual source of health care based on whether one is an
      immigrant from China, Korea, or Vietnam. 

PMID- 24858870
TI  - Response to a patient activation intervention among Spanish-speaking patients at
      a community health center in New York City.
AB  - Patient activation describes an individual's readiness to participate in their
      health care. Lower levels of activation that may contribute to poor health
      outcomes have been documented in Latino patients. We administered a brief
      activating intervention directed at Spanish-speakers that sought to improve and
      encourage question-asking during a medical visit. We used quantitative measures
      of patient attitudes supplemented with open-ended questions to evaluate the
      effectiveness of the intervention at a community health center. Post-intervention
      changes in the Patient Activation Measure (PAM) and Decision Self-Efficacy (DSE)
      were measured. Both control and intervention group PAM scores changed
      significantly, but for those at lower levels of activation, only the intervention
      group showed significant gains. For the DSE the intervention group showed
      significant changes in scores. These findings, which are supported by the
      qualitative data, suggest that the intervention helped patients who may have
      difficulty asking questions during medical visits. 

PMID- 24858872
TI  - Cervical cancer and HPV: knowledge, attitudes, beliefs, and behaviors among women
      living in Guatemala.
AB  - This study was conducted to explore knowledge, attitudes, and beliefs about
      cervical cancer, cervical cancer screening, human papillomavirus (HPV), and
      acceptance of the HPV vaccine. A purposive sample of 40 women was interviewed
      during August 2012. Fisher's exact test was used to evaluate differences among
      rural and urban women, and open-ended questions were coded independently by two
      individuals (Cohen's kappa coefficient of 0.816). Among the 22 rural and 18 urban
      women, there was limited knowledge about cervical cancer, screening, HPV, and the
      HPV vaccine. Cervical cancer was described in language related to gender,
      science, severity, or associated with having children, a uterus, or menstruation.
      All rural and most urban participants were interested in the HPV vaccine for
      themselves and their daughters. Limited awareness and knowledge about cervical
      cancer and HPV was common among Guatemalan women, highlighting the need for
      additional information prior to developing cancer prevention educational
      materials and programs. 

PMID- 24858871
TI  - Suc Khoe La Quan Trong Hon Sac Dep! Health is better than beauty! A community
      based participatory research intervention to improve cancer screening among
      Vietnamese women.
AB  - This paper examines community-based participatory research (CBPR) intervention
      approaches in promoting cancer-relevant outcomes for 102 Vietnamese women.
      Results indicated that the intervention was effective in promoting breast and
      cervical cancer knowledge, positive attitudes towards breast cancer screening,
      and breast cancer screening. Collectivism moderated the effect of the
      intervention on attitudes towards breast cancer screening. The intervention led
      to more favorable attitudes towards breast cancer screening for women with high
      levels of collectivism but not for women with low levels. Ethnic identity
      moderated the effect of the intervention on breast cancer screening: the
      intervention program led to higher probability of getting a clinical breast exam;
      however, this effect was more pronounced for women with low ethnic identity than
      for those with high ethnic identity. The study provides evidence for the
      effectiveness of culturally-tailored strategies in developing cancer screening
      interventions for the Vietnamese American population. 

PMID- 24858873
TI  - Over-the-counter but out of reach: a pharmacy-based survey of OTC syringe sales
      in Tijuana, Mexico.
AB  - Sterile syringe access is critical to HIV prevention efforts targeting injection
      drug users (IDUs) but some pharmacies do not sell syringes over-the-counter (OTC)
      even where such sales are legal. We conducted a pharmacy survey in Tijuana,
      Mexico (where OTC sales are legal) to characterize attitudes toward syringe sales
      and to explore support for expanding pharmacy-based HIV prevention efforts. Of
      203 respondents, 28% supported OTC syringe sales to IDUs and 74% said their
      pharmacy required a prescription for at least some syringe sales. Support for OTC
      syringe sales was independently associated with selling OTC syringes,
      understanding the role of sterile syringes in HIV prevention, and recognizing
      pharmacies as an important health resource for IDUs. Most respondents supported
      an expanded role for pharmacies in HIV prevention, exclusive of OTC syringe
      sales. Our study provides information for developing interventions to promote OTC
      syringe sales and expanding pharmacy-based distribution of HIV-related
      information and resources. 

PMID- 24858874
TI  - Reducing barriers to hepatitis C treatment among drug users: an integrated
      hepatitis C peer education and support program.
AB  - This report describes an innovative HCV Peer Educator Program that facilitates
      education, support, and engagement in HCV treatment among patients in an opioid
      treatment program. Integrating peer educators in a collaborative manner with
      close supervision holds promise as a model to reduce barriers to HCV treatment
      among drug users.

PMID- 24858875
TI  - Developing an integrated curriculum on the health of marginalized populations:
      successes, challenges, and next steps.
AB  - We describe the development and implementation of a novel curriculum on
      marginalization and health at an inner-city academic hospital in Toronto, Canada.
      The challenges of evaluating complex educational initiatives, particularly those
      centered on patient advocacy, are identified and potential solutions are
      discussed.

PMID- 24858876
TI  - Addressing health care disparities and access to dental care while improving
      education: schools of dentistry and federally qualified health centers.
AB  - Oral health disparities in the United States are a result of economic,
      educational, and social barriers faced by vulnerable and underserved individuals.
      The oral health care infrastructure is continuously challenged to provide access
      to quality care with a shortage of dental professionals and expanding oral health
      disparities. Federally qualified health centers (FQHC) provide oral health care
      in underserved communities, while schools of dentistry strive to provide students
      and residents with experience in underserved communities to address access to
      care issues and produce oral health professionals who will practice in these
      communities. Formal partnerships between these organizations have the potential
      to address oral health disparities, access to dental care and improve dental
      education and training. Utilizing ArcGIS (ArcMAP) software, dental schools and
      FQHC services sites located in the continental United States were geocoded to
      demonstrate geographic feasibility: on average, dental schools are within 10
      miles of 34 FQHC service sites. 

PMID- 24858877
TI  - Knowledge and perceptions of the Affordable Care Act by uninsured patients at a
      free clinic.
AB  - The Affordable Care Act (ACA) has as one of its main objectives to reduce the
      number of uninsured Americans. The understanding of the ACA reforms by uninsured
      patients will likely influence the degree of success in achieving this objective.
      This study assessed the basic knowledge and opinions regarding the ACA of
      patients at a free clinic and the impact of a brief educational intervention on
      respondents' knowledge and opinions. One hundred uninsured adult patients
      completed a brief survey about the ACA before and after viewing a video outlining
      the major features of the act. The study cohort initially performed worse than
      national polls on all knowledge questions. Significant improvement was observed
      after the educational video. Our study suggests a need for educational efforts
      directed at those individuals most likely to benefit from the ACA. We
      demonstrated that a brief intervention during a routine office visit may improve
      knowledge of the ACA. 

PMID- 24858878
TI  - Quality of life among urban children with obesity and asthma.
AB  - OBJECTIVE: To investigate quality of life (QoL) among obese asthmatic children
      and elucidate its association with lung function. METHODS: Preadolescent inner
      city children with obesity, asthma, both, or neither completed the Pediatric
      Quality of Life 4.0 (PedsQL) and Asthma Quality of Life Questionnaires and
      spirometry testing. Spirometric indices, composite and individual QoL scores were
      compared between groups using analysis of variance while proportion of children
      reporting item-specific impairment were compared by chi-squaretest. RESULTS: The
      composite QoL scores did not differ between obese asthmatics and the other study
      groups. FEV1/FVC was the lowest among obese asthmatics but did not correlate with
      QoL measures. DISCUSSION: Overall QoL in obese asthmatic preadolescents is well
      preserved. Since QoL measures did not correlate with spirometric indics, asthma
      severity may not serve as a surrogate marker of QoL. QoL evaluation should be
      incorporated in asthma management and early identification of changes may prevent
      further deterioration.

PMID- 24858879
TI  - Street outreach and other forms of engagement with literally homeless veterans.
AB  - Street outreach is one of the most direct methods of engaging homeless
      individuals, but the characteristics of those most likely to be engaged this way
      is not well-understood. Data from the Department of Veterans Affairs (VA)
      Homeless Operations Management and Evaluation System showed that of the 70,778
      literally homeless veterans engaged in VA homeless services in 2011-2012, 12%
      were through street outreach while the majority was through provider referrals
      (41%) and self-referrals (28%). Veterans engaged through street outreach had more
      extensive histories of recent homelessness, were more likely to be chronically
      homeless, and were more likely to be referred and admitted to the VA's supported
      housing program than other veterans. These findings suggest street outreach is an
      especially important approach to engaging chronic street homeless veterans in
      services and linking them to permanent supported housing. 

PMID- 24858880
TI  - Quality of hepatitis C care at an urban tertiary care medical center.
AB  - BACKGROUND: More effective treatment for hepatitis C virus (HCV) creates an
      opportunity to improve health outcomes. OBJECTIVE: To use Centers for Medicare
      and Medicaid Services (CMS)-defined HCV quality indicators (QI) as a framework to
      assess the quality of care at an urban safety net hospital. DESIGN: Retrospective
      cohort. PARTICIPANTS: Patients engaged in care (at least two outpatient visits,
      and minimum six-month follow-up time) between 2005 and 2011. Outcomes measures.
      1) HCV ribonucleic acid (RNA); 2) genotyping; 3) treatment; and 4) Hepatitis A
      and B vaccination. Study time was divided into three periods: 1) 2005-2006, 2)
      2007-2008, 3) 2009-2011. Key results. Number who met inclusion criteria: 3,018;
      13% were human immunodeficiency virus co-infected. Only 1% completed the care
      recommended in the CMS quality indicators that were evaluated. Later time periods
      were independently associated with greater rates (aHR for HCV testing, 1.15; 95%
      CI, 1.04-1.28). CONCLUSIONS: Quality of care is improving, but it remains
      suboptimal. Initiatives are needed to increase QI completion.

PMID- 24858882
TI  - Prevalence of intimate partner violence and its impact on health: female and male
      patients using a free clinic.
AB  - PURPOSE: Examine the prevalence of intimate partner violence (IPV) with physical
      and mental health indicators among free clinic patients. METHODS: A cross
      sectional study conducted via self-administered surveys. English and Spanish
      speaking women and men aged 18 to 64 years responded to standardized
      questionnaires regarding IPV, physical and mental health, depression, and
      emotional support. RESULTS: The overall prevalence of IPV was 41%. U.S.-born
      participants reported a higher prevalence of IPV (women 61%, men 69%) compared
      with the national average (women 36%, men 29%) and the non-U.S.-born or immigrant
      participants (women 39%, men 7%). Women with IPV reported poorer mental health
      but the same level of physical health functioning compared with women without
      IPV. The impact of IPV on health was somewhat different for men. CONCLUSIONS:
      Intimate partner violence is associated with poor health outcomes, especially for
      U.S.-born participants. Further research is warranted to understand causal
      mechanisms and to aid patients.

PMID- 24858881
TI  - Asthma and adaptive functioning among homeless kindergarten-aged children in
      emergency housing.
AB  - BACKGROUND: Children who experience homelessness have elevated rates of asthma, a
      risk factor for other problems. Purpose. Examine rates of asthma and its relation
      to health care use and adaptive functioning among young children staying in
      family emergency shelters. METHODS: Children and caregivers (N = 138) completed
      assessments in shelters, including measurement of child cognitive functioning,
      parent report of child health care service utilization and asthma diagnosis, and
      teacher report of child school functioning. RESULTS: Asthma diagnosis was
      reported for 21% of 4-to-6-year-old children, about twice the national and state
      prevalences. Children with asthma used more health care services and had worse
      peer relationships. Asthma did not relate to cognitive test performance or
      subsequent academic performance, or to other behavior problems in school.
      CONCLUSIONS: High rates of asthma remain an important issue for children in
      emergency family housing, a context with high levels of child risk for toxic
      stress exposure and developmental problems.

PMID- 24858883
TI  - Perspectives of older adults of low socioeconomic status on the post-hospital
      transition.
AB  - BACKGROUND: Older adults of low socioeconomic status are at high risk for poor
      post-hospital outcomes. Design. A qualitative researcher, who was also an
      outreach worker from the West Philadelphia community, conducted in-depth
      interviews with 25 participants within 30 days of their hospital discharge.
      PARTICIPANTS: Eligible participants were: 1) residents of high-poverty ZIP codes;
      2) dually eligible for Medicare and Medicaid; 3) had capacity or a caregiver who
      could be interviewed as a proxy; 4) general medicine or cardiology patients.
      RESULTS: Participants were unable to access the care and accommodations needed to
      cope with post-hospital frailty. As a result, medical disability was amplified by
      socioeconomic disability. Participants were ashamed of the resulting loss of
      control and had difficulty asking for help, particularly from potential supports
      who were perceived as emotionally controlling or judgmental. CONCLUSION:
      Strategies that address socioeconomic stressors of hospitalization and provide
      empathic support may improve the post-hospital transition for these high-risk
      individuals.

PMID- 24858884
TI  - A qualitative study of pregnancy intention and the use of contraception among
      homeless women with children.
AB  - We undertook a qualitative analysis informed by grounded theory to explore
      pregnancy intention and the barriers to contraceptive use as perceived by
      homeless women with children. Semi-structured interviews (n = 22) were performed
      in English and in Spanish. The dominant theme emerging from the interviews was a
      strong desire to avoid pregnancy while homeless. However, few women in our sample
      used contraception or accessed reproductive health care consistently. There were
      multiple barriers to using contraception and to accessing reproductive health
      care services that homeless women reported: (1) inability to prioritize health
      due to competing demands, (2) shelter-related obstacles and restrictive provider
      practices that impede access to reproductive health care services and the use of
      contraception, and (3) change in the power dynamics of sexual relationships while
      homeless, making women more vulnerable to sexual exploitation. Findings suggest a
      multifactorial approach is needed to help homeless women use contraception and
      access reproductive health services. 

PMID- 24858885
TI  - Get healthy together: a program to improve counseling for childhood obesity in
      community-based WIC clinics.
AB  - Counseling parents of overweight children is a sensitive issue that has been
      reported to be difficult for many health professionals. The Get Healthy Together
      (GHT) project involved an 18-month intervention that provided skills training and
      new tools to Women, Infants, and Children (WIC) program staff and a staff
      wellness program to improve the physical self-concept and functioning of WIC
      employees. All WIC staff from the 48 WIC clinics in New Mexico participated in
      this study. The design used random assignment to intervention or control
      condition. Staff participating in the Get Healthy Together project reported
      improved confidence in their ability to counsel parents of overweight children
      and improved counseling skills related to health behaviors. Use of the innovative
      tools provided visual aids that helped parents understand the health implications
      of their child's weight without the parents becoming defensive. These tools are
      publicly available in English and Spanish on the WIC Works Sharing Gallery
      (website:
      http://www.nal.usda.gov/wicworks/Sharing_Center/gallery/healthytogether.html). 

PMID- 24858887
TI  - Access to primary and specialty care and emergency department utilization of
      medicaid enrollees needing specialty care.
AB  - OBJECTIVE: Medicaid enrollees are more likely to use the emergency department
      (ED) than the privately insured and uninsured, yet little is known about
      enrollees' problems in accessing primary care and specialty care providers among
      those needing specialty care. DATA SOURCES: The study sample is from the 2003
      2010 Medical Expenditure Panel Survey (MEPS) of 2,733 Medicaid enrollees
      reporting a need for specialty care. METHODS: This paper estimates a two-part
      model to analyze the relationship between enrollees' access to providers and ED
      visits. PRINCIPAL FINDINGS: Perceived problems accessing a primary care physician
      are associated with ED use among Medicaid enrollees. Despite reporting need and
      facing barriers, access to specialty care is not significantly related to ED use.
      CONCLUSIONS: As states prepare for the impending expansion of Medicaid funded via
      the Affordable Care Act, they should address barriers to accessing primary care
      providers for Medicaid enrollees with high need.

PMID- 24858886
TI  - The acceptability of incorporating a youth smoking prevention intervention in the
      pediatric emergency department.
AB  - The pediatric emergency department (PED) is under-utilized as a setting in which
      to provide tobacco prevention interventions for at-risk children. We sought to
      determine the acceptability and feasibility of incorporating a brief, parental
      tobacco prevention intervention to 520 parents during the PED visit. Mean age
      (SD) of parents and children was 38.6 (7.1) and 11.5 (1.1), respectively; 47% of
      children were female; 45% were African American; 36% of parents had an annual
      income less than $25,000; 28.8% of parents were current smokers. Over 90% of
      parents said the intervention provided "useful" and "easy to understand"
      information and 97% of practitioners said it did not "interfere with clinical
      care." Given the high prevalence of parental smoking in the PED, there is a high
      likelihood that their children will initiate smoking in the future. Thus, the use
      of the PED as a venue to providing tobacco prevention interventions warrants
      further evaluation. 

PMID- 24858888
TI  - A triple play: psychological distress, physical comorbidities, and access and use
      of health services among U.S. adults with disabilities.
AB  - PURPOSE: Among adults with disabilities, we examined whether increasing levels of
      psychological distress were associated with higher estimated prevalences of
      chronic conditions, obesity, health care access, and use of preventive services.
      METHODS: We analyzed data from the 2007 Behavioral Risk Factor Surveillance
      System. The Kessler-6 scale was used to assess psychological distress. RESULTS:
      Increasing levels of psychological distress were associated with an increased
      prevalence of chronic diseases and conditions, and decreased access to health
      care and utilization of preventive services in keeping with what has been
      established for non-disabled populations. Among adults with disabilities, aged 18
      64 years and 65 years or older, increasing levels of distress were also
      associated with increased receipt of mental health treatment. However, compared
      to adults aged 18-64 years, larger proportions of older adults reported non
      receipt of mental health treatment (mild to moderate psychological distress:
      58.0% versus 70.6%; serious psychological distress: 40.5% versus 54.5%).
      CONCLUSIONS: While adults with disabilities who had increased levels of
      psychological distress were more likely to receive mental health services, they
      also had higher estimated prevalences of chronic conditions, barriers to health
      care, and non-receipt of preventive cancer screenings.

PMID- 24858889
TI  - Successful management of latent tuberculosis infection in an underserved
      community by a student-run free clinic.
AB  - The management of latent tuberculosis infection (LTBI) most commonly consists of
      a nine-month course of isoniazid (INH) therapy and is complicated by low
      adherence and completion rates. The Latent Tuberculosis Initiative at the HAVEN
      Free Clinic was developed to provide LTBI treatment to an underserved, high-risk,
      foreign-born population. We conducted a retrospective chart review to evaluate
      the program. Of 39 patients enrolled, 26 (67%) successfully completed nine months
      of INH, eight (21%) discontinued, and five (12%) were lost to follow-up. Patients
      had a median of nine encounters during the course of treatment and mean self
      reported medication adherence was 29/30 pills/month (96%). Median days-of
      treatment was 273, 95, and 63 among completion, discontinuation, and lost to
      follow-up groups, respectively (p < .0001). There was one death in the program,
      related to a complication of a diagnostic procedure in a patient who had
      developed INH toxicity. These results are comparable to the most successful
      published programs (50-65% six-month completion rates), suggesting that student
      run clinics serving high-risk populations may contribute to LTBI management and
      TB control efforts. 

PMID- 24858890
TI  - Prioritization of inpatient hospital services to prisoners: a method for
      justifying care and costs.
AB  - As a response to rising health care costs and substantial cuts in state funding
      for correctional health care in Texas, we developed and applied a process
      framework for systematically prioritizing the provision of inpatient hospital
      services to prisoners. Specifically, all inpatient services provided from
      September 2009 through August 2011 at the University of Texas Medical
      Branch/Texas Department of Criminal Justice Hospital were sorted according to
      levels of care consistent with those previously defined by the Oregon Department
      of Corrections and the Federal Bureau of Prisons. Nearly all inpatient services
      (94%) were deemed medically mandatory (Level 1) or medically necessary (Level 2).
      These services must be funded to ensure an adequate level of care, and capitated
      funding mechanisms may not be sufficiently flexible to cover their costs.
      Correctional health care systems may adapt the framework used here to inform
      state policymakers regarding provision of inpatient services and funding
      requirements. 

PMID- 24858892
TI  - AmeriCorps Members increase enrollment in Medicaid/CHIP and preventive care
      utilization at a community health center.
AB  - BACKGROUND: Uninsured children have less access than others to primary care;
      Latino children are more likely than non-Latino children to be uninsured.
      OBJECTIVES: 1. Determine whether case management (CM) by AmeriCorps Members (ACM)
      increases enrollment of children in Medicaid/CHIP at a federally qualified
      community health center (FQHC); 2. Identify factors associated with non
      enrollment; 3. Compare health care utilization by enrolled and non-enrolled
      children. METHODS: Parents of uninsured children at two urban FQHCs serving
      primarily Latino families were offered CM assistance for enrollment in
      Medicaid/CHIP at one of the clinics. Application instructions alone were provided
      at the other clinic. Results. Of 107 children at the CM clinic, 74% were enrolled
      compared with 26% of the 96 from the non-CM clinic. Non-enrolled children
      completed fewer preventive care visits than enrolled children despite sliding
      fees at both FQHCs. CONCLUSION: Case management by ACM is a low-cost, effective
      approach to increasing access to care for Latino children.

PMID- 24858891
TI  - The effect of involvement in a student-run free clinic project on attitudes
      toward the underserved and interest in primary care.
AB  - METHODS: The authors designed a survey instrument to examine the effect of
      involvement in a student-run free clinic project (SRFCP) on medical student self
      reported attitudes toward the underserved and interest in primary care. From 2001
      2010, first-and second-year medical students in an introductory service-learning
      elective course rated each of 15 statements on a seven-point Likert scale
      pre/post survey. Wilcoxon's signed rank test was performed on all matched pairs
      and an intent-to-treat analysis included unmatched pairs. RESULTS: The response
      rate was 97.9%, with 914 of 934 students enrolled participating. Significant
      increases were seen in each of the 15 items in matched pre/post survey pairs, N =
      433 (47.4%), or with an intent-to-treat analysis, N = 914 (p <= .002 for all).
      CONCLUSIONS: This study found that medical student involvement in a SRFCP
      improved student knowledge, skills, attitudes and self-efficacy with the
      underserved, interest in work with the underserved after graduation, and interest
      in primary care.

PMID- 24858893
TI  - Health care concerns of rural childhood cancer survivors.
AB  - BACKGROUND: Geographic isolation may limit health care access due to burdens of
      time, cost and travel distance. We explored rural childhood cancer survivors'
      experiences and concerns about accessing affordable, quality care. METHODS: In
      depth, semi-structured telephone interviews were conducted with 17 rural adult
      survivors recruited from the Utah Cancer Registry. Interviews were recorded,
      transcribed, and content analyzed with NVivo 9 by two coders (kappa = 0.93).
      RESULTS: Two primary themes emerged: (1) concerns about health care quality and
      (2) geographic and insurance issues. Within these main themes, we identified
      salient sub-themes: quality of primary care, patient-provider trust, specialty
      care access, travel burdens, and financial and insurance concerns. CONCLUSIONS:
      Rural childhood cancer survivors have concerns about local health care services,
      but are willing to travel several hours to receive care. Partnerships between
      local primary care and cancer specialty providers via telemedicine that
      incorporate survivor care plans could improve risk-based care for rural
      survivors.

PMID- 24858894
TI  - Relational discord in urban primary care: prevalence rates and psychiatric
      comorbidities.
AB  - The current study primarily assesses uninsured, low-income patients (n = 125) in
      a primary care practice. Despite the knowledge that family relationships affect
      the management and outcomes of chronic illness, the rates of relational discord
      among primary care patients are unknown. Findings reveal that 54% of patients met
      criteria for problematic family functioning, while 40% of those in a romantic
      relationship reported relationship distress. In addition, 67% reported
      depression, 32% reported clinical levels of anxiety, and 33% at-risk alcohol use.
      Researchers used latent class analysis to explore characteristics of the sample,
      which revealed four classes. Comparisons with prior research with similar
      populations are made and implications for behavioral health providers working
      within primary care are discussed. 

PMID- 24858895
TI  - Mission, margin, and the role of consumer governance in decision-making at
      community health centers.
AB  - OBJECTIVE: We explore the role of consumer trustees in decision-making as
      community health centers (CHCs) work to navigate the tension between pursuing
      their mission to provide primary care to all regardless of ability to pay and
      maintaining their limited finances. METHODS: We interviewed 30 trustees from 16
      CHCs in 14 different states, asking extensively about decision-making processes
      at their CHC related to services and finances, as well as perceived advantages
      and disadvantages of consumer governance. RESULTS: Respondents described mission
      dominant, margin-dominant, and balanced decision-making philosophies, and
      different decision-making pathways for service provision and finances. Consumer
      trustees were lauded for their role in informing the board of service quality and
      community needs, but criticized for being professionally unskilled and exhibiting
      a lack of objective decision-making. CONCLUSIONS: While CHC boards do play a role
      in navigating the tension between mission and margin, executive directors and
      staff appear to be more influential.

PMID- 24858897
TI  - Populations whose primary language is not English.

PMID- 24858898
TI  - Physiological responses of Manila clams Venerupis (=Ruditapes) philippinarum with
      varying parasite Perkinsus olseni burden to toxic algal Alexandrium ostenfeldii
      exposure.
AB  - Manila clam stock from Arcachon Bay, France, is declining, as is commercial
      harvest. To understand the role of environmental biotic interactions in this
      decrease, effects of a toxic dinoflagellate, Alexandrium ostenfeldii, which
      blooms regularly in Arcachon bay, and the interaction with perkinsosis on clam
      physiology were investigated. Manila clams from Arcachon Bay, with variable
      natural levels of perkinsosis, were exposed for seven days to a mix of the
      nutritious microalga T-Iso and the toxic dinoflagellate A. ostenfeldii, a
      producer of spirolides, followed by seven days of depuration fed only T-Iso.
      Following sacrifice and quantification of protozoan parasite Perkinsus olseni
      burden, clams were divided into two groups according to intensity of the
      infection ("Light-Moderate" and "Moderate-Heavy"). Hemocyte and plasma responses,
      digestive enzyme activities, antioxidant enzyme activities in gills, and
      histopathological responses were analyzed. Reactive oxygen species (ROS)
      production in hemocytes and catalase (CAT) activity in gills increased with P.
      olseni intensity of infection in control clams fed T-Iso, but did not vary among
      A. ostenfeldii-exposed clams. Exposure to A. ostenfeldii caused tissue
      alterations associated with an inflammatory response and modifications in
      hemocyte morphology. In the gills, superoxide dismutase (SOD) activity decreased,
      and an increase in brown cell occurrence was seen, suggesting oxidative stress.
      Observations of hemocytes and brown cells in tissues during exposure and
      depuration suggest involvement of both cell types in detoxication processes.
      Results suggest that exposure to A. ostenfeldii disrupted the pro-/anti-oxidant
      response of clams to heavy P. olseni intensity. In addition, depressed
      mitochondrial membrane potential (MMP) in hemocytes of clams exposed to A.
      ostenfeldii suggests that mitochondrial functions are regulated to maintain
      homeostasis of digestive enzyme activity and condition index. 

PMID- 24858899
TI  - Photosynthetic and molecular responses of the marine diatom Thalassiosira
      pseudonana to triphenyltin exposure.
AB  - This study aimed to investigate the responses of the marine diatom Thalassiosira
      pseudonana upon waterborne exposure to triphenyltin chloride (TPTCl) through
      determining their photosynthetic response, growth performance, and expressions of
      genes and proteins. Based on the growth inhibition test, the 96-h IC50 (i.e.,
      median inhibition concentration) was found to be 1.09 MUg/L (95% confidence
      interval (CI): 0.89-1.34 MUg/L). According to photosynthetic parameters, the 96-h
      EC50s (i.e., median effect concentrations) were estimated at 1.54 MUg/L (95% CI:
      1.40-1.69 MUg/L) and 1.51 MUg/L (95% CI: 1.44-1.58 MUg/L) for the maximum quantum
      yield of photosystem II (PSII) photochemistry (PhiPo) and the effective quantum
      yield of photochemical energy conversion in PSII (Phi2), respectively. Non
      photochemical quenching in the algae was increased at low concentrations of TPTCl
      (0.5-1.0 MUg/L) but it decreased gradually when the TPTCl concentration further
      increased from 1.0 to 2.5 MUg/L. Results of gene expressions showed that lipid
      metabolism related genes were not influenced by TPTCl at 0.5 or 1.0 MUg/L, while
      silica shell formation genes were down-regulated at 0.5 MUg/L. Photosynthesis
      related genes were up-regulated at 0.5 MUg/L TPTCl but were down-regulated at 1.0
      MUg/L TPTCl. Proteomics analysis revealed that relatively less proteins could be
      detected after exposure to 1.0 MUg/L TPTCl (only about 50-60 spots) compared with
      that observed in the 0.5MUg/L TPTCl treatment and two control groups (each with
      about 290-300 protein spots). At 0.5 MUg/L TPTCl, five proteins were
      differentially expressed when compared with the seawater control and solvent
      control, and most of these proteins are involved in defence function to protect
      the biological systems from reactive oxygen species that generated by TPTCl.
      These proteins include oxygen-evolving enhancer protein 1 precursor, fucoxanthin
      chlorophyll a/c protein - LI818 clade, and mitochondrial manganese superoxide
      dismutase, which can function to maintain the capacity of PSII and stabilize the
      photosynthesis efficiency as reflected by the unchanged PhiPo and Phi2 values at
      0.5 MUg/L TPTCl. In contrast, the excess toxicity that caused by TPTCl at the
      high concentration (1.0 MUg/L TPTCl) might directly damage the proteins, inhibit
      their expression, and/or cause the suppression of metabolism as indicated by the
      down-regulation of most studied proteins and genes, which could ultimately
      inhibit the photosynthesis and growth of the algae. Overall, this study
      comprehensively elucidated the toxicity effects of TPT on T. pseudonana, and
      partially revealed the molecular toxic mechanisms and corresponding defence
      responses in this model algal species.

PMID- 24858901
TI  - Fever screening of seasonal influenza patients using a cost-effective thermopile
      array with small pixels for close-range thermometry.
AB  - OBJECTIVE: Infrared thermography systems have been used for fever screening at
      many airports since the outbreak of severe acute respiratory syndrome (SARS) in
      2003. However, many of these systems are expensive and non-portable. Therefore,
      we developed a cost-effective and compact (2.9 * 5.8 * 2.0 cm) thermopile array
      for fever screening of patients with infectious diseases in the clinical setting.
      METHODS: The array was created with small pixels (48 * 47 = 2256 pixels)
      fabricated on a silicon wafer using microelectromechanical systems technology. We
      tested this array on 155 febrile and afebrile patients (35.4 degrees C <=
      axillary temperature <= 39.3 degrees C) with seasonal influenza at the Japan Self
      Defense Forces Central Hospital. RESULTS: The maximum facial temperature,
      measured by the array at 0.3 m from the subject, exhibited a positive correlation
      with axillary temperature measured using a contact-type thermometer (r = 0.71, p
      < 0.01). The sensitivity and specificity of the thermopile array in identifying
      the febrile subjects were 80.5% and 93.3%, respectively, setting the threshold
      cut-off of maximum facial temperature at an appropriate value. CONCLUSIONS: Our
      cost-effective thermopile array appears promising for future close-range fever
      screening of patients with infectious diseases at primary care doctor clinics,
      health care centers, and quarantine stations in developing and developed
      countries.

PMID- 24858902
TI  - Cutaneous leishmaniasis in Mullaitivu, Sri Lanka: a missing endemic district in
      the leishmaniasis surveillance system.
AB  - The purpose of this study was to describe the emergence of cutaneous
      leishmaniasis in a district of Sri Lanka, documented at the national level as
      having zero incidence. We analyzed data from the Sri Lanka Army (SLA) to describe
      reported cases of cutaneous leishmaniasis for all armed forces personnel located
      in all 24 districts of Sri Lanka. These data are not included in the National
      Surveillance System. From January 2011 through February 2013, 314 armed forces
      personnel were confirmed as having leishmaniasis. Of these, 223 (81.4%) were
      working within the district of Mullaitivu at the time of investigation and
      another 21 (6.5%) reported that the lesion first appeared when they were working
      in Mullaitivu. The reported cumulative annual incidence of leishmaniasis among
      the army population was 7.5 per 10000, while in the general area of Mullaitivu
      the incidence was 234 per 10000. Leishmaniasis is emerging in epidemic
      proportions in Mullaitivu and is still not detected through the public health
      surveillance system. Urgent attention directed at disease surveillance and
      control activities is needed to control this emerging public health threat. 

PMID- 24858900
TI  - Synchronous occurrence of medullary and papillary carcinoma of the thyroid in a
      patient with cutaneous melanoma: determination of BRAFV600E in peripheral blood
      and tissues. Report of a case and review of the literature.
AB  - The purpose of this study is to describe a case of concurrent medullary and
      papillary thyroid carcinoma (MTC and PTC) and cutaneous melanoma and to analyze
      BRAF(V600E) mutation in plasma and tissues. We report the clinical history and
      the laboratory, imaging, and histopathological findings of a 47-year-old man
      affected by multinodular goiter. BRAF(V600E)-mutated DNA was quantified in plasma
      samples and in cancer sections by quantitative real-time polymerase chain
      reaction (qPCR). At ultrasound examination, the dominant right nodule of the
      thyroid was weakly hyperechoic and hypervascularized, while the left one was
      hypoechoic without internal vascularization. Regional lymphadenomegalia was not
      detected. Basal plasma calcitonin was elevated, and the patient underwent total
      thyroidectomy and resection of central cervical lymph nodes. Histopathological
      examination identified two distinct foci of MTC and PTC and micrometastasis of
      well-differentiated carcinoma in one of the six resected lymph nodes. RET proto
      oncogene germline mutations were not detected. Cutaneous melanoma of the thorax
      was subsequently diagnosed. BRAF(V600E) tissue DNA was detected in PTC and
      melanoma but not in MTC. The cell-free plasma percentage of BRAF(V600E) DNA was
      detected in pre-thyroidectomy peripheral blood and was drastically reduced after
      cancer treatments. This study confirms the occurrence of synchronous MTC and PTC
      and is the first evidence of the co-existence of melanoma and distinct thyroid
      cancers of different origin. BRAF(V600E) allele was detected in PTC and melanoma
      but not in MTC tissues. BRAF(V600E) molecular quantification in pre- and post
      treatment blood supports our previous data, suggesting its possible role in
      diagnosis and follow-up of BRAF-positive tumors. 

PMID- 24858903
TI  - Bacteriological characterization of a Mycobacterium parascrofulaceum strain
      isolated from a Chinese pneumonia patient.
AB  - BACKGROUND: A Mycobacterium parascrofulaceum strain was isolated from a pneumonia
      patient-the first such reported case from China. The bacteriological
      characteristics of the strain were determined. METHODS: Species identification
      was performed by homologue gene sequence comparison, then a series of biochemical
      tests was conducted to elucidate the bacteriological characteristics. Drug
      susceptibility and pathogenicity to mice of the strain were tested. RESULTS: The
      clinical M. parascrofulaceum strain presented a very similar phenotypic profile
      to that of Mycobacterium scrofulaceum. The M. parascrofulaceum strain was
      sensitive to rifabutin, rifapentine, clarithromycin, azithromycin, cefoxitin, and
      moxifloxacin in vitro. At week 2 post-infection, the lung tissues of mice
      demonstrated a local inflammatory response denoted by peri-bronchiolar
      inflammatory infiltrates. At weeks 4 and 8, the lung tissues showed peri
      bronchiolar inflammatory infiltrates with large aggregates of lymphocytes and
      part of the tissue showed granulomatous lesions; there was no appreciable
      necrosis. The colony-forming units (CFU) count of infected lung and spleen
      increased gradually during the 8 weeks of the experiment. CONCLUSIONS: The M.
      parascrofulaceum strain isolated in China was sensitive to rifabutin,
      rifapentine, clarithromycin, azithromycin, cefoxitin, and moxifloxacin. The
      mycobacteria were capable of proliferating in mice and could lead to pathological
      changes in the lungs of the mice.

PMID- 24858904
TI  - Major emerging and re-emerging zoonoses in China: a matter of global health and
      socioeconomic development for 1.3 billion.
AB  - Emerging and re-emerging zoonoses are a significant public health concern and
      cause considerable socioeconomic problems globally. The emergence of severe acute
      respiratory syndrome (SARS), highly pathogenic avian influenza (HPAI) H5N1, avian
      influenza H7N9, and severe fever with thrombocytopenia syndrome (SFTS), and the
      re-emergence of rabies, brucellosis, and other zoonoses have had a significant
      effect on the national economy and public health in China, and have affected
      other countries. Contributing factors that continue to affect emerging and re
      emerging zoonoses in China include social and environmental factors and microbial
      evolution, such as population growth, urbanization, deforestation, livestock
      production, food safety, climate change, and pathogen mutation. The Chinese
      government has devised new strategies and has taken measures to deal with the
      challenges of these diseases, including the issuing of laws and regulations,
      establishment of disease reporting systems, implementation of special projects
      for major infectious diseases, interdisciplinary and international cooperation,
      exotic disease surveillance, and health education. These strategies and measures
      can serve as models for the surveillance and response to continuing threats from
      emerging and re-emerging zoonoses in other countries. 

PMID- 24858905
TI  - Genetic similarity of island populations of tent caterpillars during successive
      outbreaks.
AB  - Cyclic or fluctuating populations experience regular periods of low population
      density. Genetic bottlenecks during these periods could give rise to temporal or
      spatial genetic differentiation of populations. High levels of movement among
      increasing populations, however, could ameliorate any differences and could also
      synchronize the dynamics of geographically separated populations. We use
      microsatellite markers to investigate the genetic differentiation of four island
      and one mainland population of western tent caterpillars, Malacosoma californicum
      pluviale, in two periods of peak or pre-peak density separated by 8 years.
      Populations showed high levels of genetic variation and little genetic
      differentiation either temporally between peaks or spatially among sites.
      Mitochondrial haplotypes were also shared between one island population and one
      mainland population in the two years studied. An isolation-by-distance analysis
      showed the FST values of the two geographically closest populations to have the
      highest level of differentiation in both years. We conclude that high levels of
      dispersal among populations maintain both synchrony of population dynamics and
      override potential genetic differentiation that might occur during population
      troughs. As far we are aware, this is the first time that genetic similarity
      between temporally separated population outbreaks in insects has been
      investigated. A review of genetic data for both vertebrate and invertebrate
      species of cyclic animals shows that a lack of spatial genetic differentiation is
      typical, and may result from high levels of dispersal associated with fluctuating
      dynamics. 

PMID- 24858907
TI  - Deletion of ameloblastin exon 6 is associated with amelogenesis imperfecta.
AB  - Amelogenesis imperfecta (AI) describes a heterogeneous group of inherited dental
      enamel defects reflecting failure of normal amelogenesis. Ameloblastin (AMBN) is
      the second most abundant enamel matrix protein expressed during amelogenesis. The
      pivotal role of AMBN in amelogenesis has been confirmed experimentally using
      mouse models. However, no AMBN mutations have been associated with human AI.
      Using autozygosity mapping and exome sequencing, we identified genomic deletion
      of AMBN exon 6 in a second cousin consanguineous family with three of the six
      children having hypoplastic AI. The genomic deletion corresponds to an in-frame
      deletion of 79 amino acids, shortening the protein from 447 to 368 residues.
      Exfoliated primary teeth (unmatched to genotype) were available from family
      members. The most severely affected had thin, aprismatic enamel (similar to that
      reported in mice homozygous for Ambn lacking exons 5 and 6). Other teeth
      exhibited thicker but largely aprismatic enamel. One tooth had apparently normal
      enamel. It has been suggested that AMBN may function in bone development. No
      clinically obvious bone or other co-segregating health problems were identified
      in the family investigated. This study confirms for the first time that AMBN
      mutations cause non-syndromic human AI and that mouse models with disrupted Ambn
      function are valid. 

PMID- 24858908
TI  - X inactivation plays a major role in the gender bias in somatic expansion in a
      mouse model of the fragile X-related disorders: implications for the mechanism of
      repeat expansion.
AB  - The Fragile X-related disorders are X-linked disorders resulting from the
      inheritance of FMR1 alleles with >54 CGG/CCG repeats in their 5' UTR. The repeats
      expand both somatically and on intergenerational transmission and increased
      repeat numbers are associated with increased risk of disease and increased risk
      of further expansion. The mechanism responsible for expansion is unknown. Here,
      we show in a knockin mouse model of these disorders that somatic expansion is
      much less common in females than in males. We show that this is due in large part
      to the fact that expansions occur only when the repeat is on the active X
      chromosome. However, even when this is taken into account, expansions in females
      are still less common than expected. This additional gender effect is not due to
      a protective effect of estrogen, a deleterious effect of testosterone or to
      differences in the expression of the Fmr1 gene or a variety of X-linked and
      autosomal DNA repair genes. However, our data do suggest that a higher level of
      expression of genes that protect against oxidative damage in females may
      contribute to their lower levels of expansion. Whatever the basis, our data
      suggest that the risk for somatic expansion may be lower in women than it is in
      men. This could help explain the reduced penetrance of some aspects of disease
      pathology in women. The fact that expansion only occurs when the Fmr1 allele is
      on the active X chromosome has important implications for the mechanism of repeat
      expansion. 

PMID- 24858909
TI  - Disruption of myocardial Gata4 and Tbx5 results in defects in cardiomyocyte
      proliferation and atrioventricular septation.
AB  - Mutations in GATA4 and TBX5 are associated with congenital heart defects in
      humans. Interaction between GATA4 and TBX5 is important for normal cardiac
      septation, but the underlying molecular mechanisms are not well understood. Here,
      we show that Gata4 and Tbx5 are co-expressed in the embryonic atria and
      ventricle, but after E15.5, ventricular expression of Tbx5 decreases. Co
      localization and co-immunoprecipitation studies demonstrate an interaction of
      Gata4 and Tbx5 in the developing atria and ventricles, but the ventricular
      interaction declines after E14.5. Gata4(+/-);Tbx5(+/-) mouse embryos display
      decreased atrial and ventricular myocardial thickness at E11.5, prior to cardiac
      septation. To determine the cell lineage in which the interaction was
      functionally significant in vivo, mice heterozygous for Gata4 in the myocardium
      or endocardium and heterozygous for Tbx5 (Gata4(MyoDel/wt);Tbx5(+/-) and
      Gata4(EndoDel/wt);Tbx5(+/-), respectively) were generated.
      Gata4(MyoDel/wt);Tbx5(+/-) mice displayed embryonic lethality, thin myocardium
      with reduced cell proliferation, and atrioventricular septation defects similar
      to Gata4;Tbx5 compound heterozygotes while Gata4(EndoDel/wt);Tbx5(+/-) embryos
      were normal. Cdk4 and Cdk2, cyclin-dependent kinases required for myocardial
      development and septation were reduced in Gata4(+/-);Tbx5(+/-) hearts. Cdk4 is a
      known direct target of Gata4 and the regulation of Cdk2 in the developing heart
      has not been studied. Chromatin immunoprecipitation and transactivation studies
      demonstrate that Gata4 and Tbx5 directly regulate Cdk4 while only Tbx5 activates
      Cdk2 expression. These findings highlight the mechanisms by which disruption of
      the Gata4 and Tbx5 interaction in the myocardium contributes to cardiac septation
      defects in humans. 

PMID- 24858910
TI  - The survival gene MED4 explains low penetrance retinoblastoma in patients with
      large RB1 deletion.
AB  - Retinoblastoma is a non-hereditary as well as an inherited pediatric tumor of the
      developing retina resulting from the inactivation of both copies of the RB1 tumor
      suppressor gene. Familial retinoblastoma is a highly penetrant genetic disease
      that usually develops by carrying germline mutations that inactivate one allele
      of the RB1 gene, leading to multiple retinoblastomas. However, large and complete
      germline RB1 deletions are associated with low or no tumor risk for reasons that
      remain unknown. In this study, we define a minimal genomic region associated with
      this low penetrance. This region encompasses few genes including MED4 a subunit
      of the mediator complex. We further show that retinoblastoma RB1 -/- cells cannot
      survive in the absence of MED4, both in vitro and in orthotopic xenograft models
      in vivo, therefore identifying MED4 as a survival gene in retinoblastoma. We
      propose that the contiguous loss of the adjacent retinoblastoma gene, MED4,
      explains the low penetrance in patients with large deletions that include both
      RB1 and MED4. Our findings also point to another synthetic lethal target in
      tumors with inactivated RB1 and highlight the importance of collateral damage in
      carcinogenesis. 

PMID- 24858911
TI  - Kidney cancer mortality and ionizing radiation among French and German uranium
      miners.
AB  - The investigation of potential adverse health effects of occupational exposures
      to ionizing radiation, on uranium miners, is an important area of research. Radon
      is a well-known carcinogen for lung, but the link between radiation exposure and
      other diseases remains controversial, particularly for kidney cancer. The aims of
      this study were therefore to perform external kidney cancer mortality analyses
      and to assess the relationship between occupational radiation exposure and kidney
      cancer mortality, using competing risks methodology, from two uranium miners
      cohorts. The French (n = 3,377) and German (n = 58,986) cohorts of uranium miners
      included 11 and 174 deaths from kidney cancer. For each cohort, the excess of
      kidney cancer mortality has been assessed by standardized mortality ratio (SMR)
      corrected for the probability of known causes of death. The associations between
      cumulative occupational radiation exposures (radon, external gamma radiation and
      long-lived radionuclides) or kidney equivalent doses and both the cause-specific
      hazard and the probability of occurrence of kidney cancer death have been
      estimated with Cox and Fine and Gray models adjusted to date of birth and
      considering the attained age as the timescale. No significant excess of kidney
      cancer mortality has been observed neither in the French cohort (SMR = 1.49, 95 %
      confidence interval [0.73; 2.67]) nor in the German cohort (SMR = 0.91 [0.77;
      1.06]). Moreover, no significant association between kidney cancer mortality and
      any type of occupational radiation exposure or kidney equivalent dose has been
      observed. Future analyses based on further follow-up updates and/or large pooled
      cohorts should allow us to confirm or not the absence of association. 

PMID- 24858912
TI  - Comparison of health services use associated with ziprasidone and olanzapine
      among schizophrenia and bipolar disorder patients in the USA.
AB  - BACKGROUND AND OBJECTIVES: Ziprasidone is increasingly used for the treatment of
      schizophrenia and bipolar disorder. The purpose of this study was to compare
      healthcare costs and use associated with ziprasidone and olanzapine. METHODS:
      Ziprasidone and olanzapine treatment episodes of schizophrenia and bipolar
      disorder patients were identified in the 01/2007-12/2010 IMS LifeLinkTM Database.
      The period of analysis for each episode has three components: 6 months prior to
      the episode initiation date (pre-episode period), 1 month immediately following
      the episode initiation date (initiation month), and up to 12 months after the end
      of the initiation month (follow-up period). Ordinary least squares regressions,
      general linear models, and two-part models were used to compare various types of
      costs (2007 US$) associated with the use of ziprasidone and olanzapine. Logistic
      regressions, Poisson regressions, and Hurdle models were used to compare the
      number of emergency department (ED) visits and hospitalizations associated with
      each drug. RESULTS: We identified 7,138 (46.93 %) ziprasidone episodes and 8,072
      (53.07 %) olanzapine episodes, and found that patients using ziprasidone were
      significantly younger (41.50 vs. 45.38 years) and were significantly less likely
      to be male (29.81 vs. 44.21 %). Regression analysis showed no significant
      differences in total costs between the two drugs. However, ziprasidone was
      associated with significantly higher medication costs (US$232, p < 0.01) and
      outpatient costs (US$501, p < 0.05), yet lower ED costs (-US$73, p < 0.05).
      Ziprasidone was also associated with fewer ED visits (0.266, p < 0.001) and
      hospitalizations (1.117, p < 0.001). CONCLUSIONS: Ziprasidone is associated with
      higher medication costs and outpatient costs than olanzapine; however, it reduces
      patients' use of ED and inpatient services.

PMID- 24858914
TI  - The effect of personal protective equipment on emergency airway management by
      emergency physicians: a mannequin study.
AB  - OBJECTIVE: Emergency medical personnel are at risk of secondary contamination
      when treating victims of chemical-biological-radiological-nuclear incidents.
      Hence, it is crucial to train them on the appropriate management of patients
      involved in chemical-biological-radiological-nuclear incidents. Personal
      protective equipment (PPE) plays an important role in treating patients suffering
      from various types of poisoning. However, very few studies have examined whether
      the use of PPE impedes airway management in an emergency department setting. The
      present study evaluated the effect of PPE on physicians' performance of emergency
      airway management using mannequins. METHODS: Forty emergency physicians with 1-4
      years of experience participated, and were divided by years of experience (1-2
      vs. 3-4 years). Each participant both intubated a tracheal tube and inserted a
      laryngeal mask airway into a mannequin, with and without wearing protection using
      preassembled intubation aids. The intubation time for both methods was assessed
      along with participants' preferences and experiences in airway management.
      RESULTS: The mean (SD) times to successful tracheal tube/mask placement with and
      without protection were similar [tracheal tube: 17.86 s (6.38) vs. 17.83 s
      (11.13), P=0.99; laryngeal mask: 10.51 s (4.39) vs. 9.65 s (3.29), P=0.32].
      CONCLUSION: Protective equipment had no effect on physicians' emergency airway
      placement time. The effect of wearing PPE is limited if postintubation care is
      excluded from the evaluation. Furthermore, intubation experience influenced
      participants' preferred approach for airway management.

PMID- 24858913
TI  - MNSs blood group glycophorin variants in Taiwan: a genotype-serotype correlation
      study of 'Mi(a)' and St(a) with report of two new alleles for St(a).
AB  - BACKGROUND: Glycophorin variants of the MNSs blood group are important in Taiwan.
      For more than 20 years, screening for the most frequent irregular antibody, anti
      ''Mi(a)', has been conducted by using 'Mi(a)'(+) RBCs, with a significant
      success. However, the sensitivity and the specificity of this screening strategy
      have never been validated, and the true incidences of different glycophorin
      variants in Taiwan have been in controversy. Also, the significance of another
      less frequent and usually separately reported variant, St(a), has never been
      evaluated. METHODOLOGY/PRINCIPAL FINDINGS: We ran a population-based screening
      (from unselected patients in our hospital) for MNSs blood group glycophorin
      variants by PCR-sequencing method. GP.Mur (Mil.III) was confirmed by sequence
      from 57 out of 1027 samples (5.6%), and there was no other Miltenberger subtype
      glycophorin variant found. Glycophorin variant St(a) was found from 35 out of
      1027 samples (3.4%). In contrast to anti-'Mi(a)', which is the most frequently
      identified irregular antibody in Taiwan, the prevalence of anti-St(a) was only
      0.13% as determined by serologic method. In addition, two new alleles for St(a)
      were found and reported. CONCLUSION/SIGNIFICANCE: We confirm the long-standing
      assumption that GP.Mur is the only prevalent Miltenberger subtype in Taiwan. The
      current anti-'Mi(a)' screening method used in Taiwan, although neither sensitive
      nor specific, is still a suitable practice. Although St(a) antigen has a high
      prevalence in Taiwan, routine screening for anti-St(a) is not warranted based on
      current evidence.

PMID- 24858915
TI  - The accuracy of renal point of care ultrasound to detect hydronephrosis in
      children with a urinary tract infection.
AB  - The objective of this study was to investigate the accuracy of renal point of
      care ultrasound (POCUS) for the detection of hydronephrosis in children with a
      urinary tract infection (UTI). We prospectively included all patients with a
      final diagnosis of UTI who visited our pediatric emergency department between
      November 2009 and April 2011. Emergency physicians were encouraged to perform a
      renal POCUS during these visits, and a follow-up renal ultrasonography was
      performed by a radiologist who was blinded to the results of POCUS. We calculated
      the accuracy of POCUS to detect hydronephrosis (renal pelvis enlargement >=10
      mm). We included 433 UTI visits, and 382 (88.2%) POCUS were performed. The
      sensitivity and the specificity were 76.5% (95% confidence interval: 58.1-94.6%)
      and 97.2% (95.2-99.2%), respectively. The positive and the negative predictive
      values were 59.1% (36.4-79.3%) and 98.8% (97.7-99.9%), respectively. Renal POCUS
      might be used to rule out hydronephrosis in pediatric UTI. 

PMID- 24858916
TI  - The moderating effect of stimulus attractiveness on the effect of alcohol
      consumption on attractiveness ratings.
AB  - AIMS: To explore the enhancing effect of alcohol consumption on attractiveness
      ratings, in that few studies on the Beer Goggles effect control the stimuli
      attractiveness level and researchers have seldom considered extending the effect
      to stimuli other than faces. METHODS: Male and female participants (n = 103) were
      randomly assigned to alcohol consumption or placebo groups. Both groups were
      asked to assess the attractiveness of two types of pictures (faces and
      landscapes) with three levels of attractiveness for each stimulus category (high,
      moderate and low). RESULTS: We found significant interactions between beverage
      type and attractiveness level. Attractiveness ratings for moderate- and low
      attractiveness faces were significantly higher in the alcohol compared with
      placebo condition, while there was no significant difference for high
      attractiveness stimuli between these two conditions. As for landscapes, only low
      attractiveness stimuli were rated significantly higher in the alcohol condition.
      CONCLUSION: Whether or not alcohol consumption leads to an increase in
      attractiveness ratings depends on the initial attractiveness of the stimulus
      materials. Alcohol consumption tends to affect ratings for stimuli with
      relatively low attractiveness. Furthermore, this effect is not limited to faces;
      it extends to other types of stimuli like landscapes.

PMID- 24858917
TI  - In vivo and in vitro studies suggest a possible involvement of HPV infection in
      the early stage of breast carcinogenesis via APOBEC3B induction.
AB  - High prevalence of infection with high-risk human papilloma virus (HPV) ranging
      from 25 to 100% (average 31%) was observed in breast cancer (BC) patients in
      Singapore using novel DNA chip technology. Early stage of BC demonstrated higher
      HPV positivity, and BC positive for estrogen receptor (ER) showed significantly
      higher HPV infection rate. This unique association of HPV with BC in vivo
      prompted us to investigate a possible involvement of HPV in early stages of
      breast carcinogenesis. Using normal breast epithelial cells stably transfected
      with HPV-18, we showed apparent upregulation of mRNA for the cytidine deaminase,
      APOBEC3B (A3B) which is reported to be a source of mutations in BC. HPV-induced
      A3B overexpression caused significant gammaH2AX focus formation, and DNA breaks
      which were cancelled by shRNA to HPV18 E6, E7 and A3B. These results strongly
      suggest an active involvement of HPV in the early stage of BC carcinogenesis via
      A3B induction. 

PMID- 24858919
TI  - Global gene expression analysis of long-term stationary phase effects in E. coli
      K12 MG1655.
AB  - Global gene expression was monitored in long-term stationary phase (LSP) cells of
      E. coli K12 MG1655 and compared with stationary phase (SP) cells that were sub
      cultured without prolonged delay to get an insight into the survival strategies
      of LSP cells. The experiments were carried out using both LB medium and LB
      supplemented with 10% of glycerol. In both the media the LSP cells showed
      decreased growth rate compared to SP cells. DNA microarray analysis of LSP cells
      in both the media resulted in the up- and down-regulation of several genes in LSP
      cells compared to their respective SP cells in the corresponding media. In LSP
      cells grown in LB 204 genes whereas cells grown in LB plus glycerol 321 genes
      were differentially regulated compared to the SP cells. Comparison of these
      differentially regulated genes indicated that irrespective of the medium used for
      growth in LSP cells expression of 95 genes (22 genes up-regulated and 73 down
      regulated) were differentially regulated. These 95 genes could be associated with
      LSP status of the cells and are likely to influence survival and growth
      characteristics of LSP cells. This is indeed so since the up- and down-regulated
      genes include genes that protect E. coli LSP cells from stationary phase stress
      and genes that would help to recover from stress when transferred into fresh
      medium. The growth phenotype in LSP cells could be attributed to up-regulation of
      genes coding for insertion sequences that confer beneficial effects during
      starvation, genes coding for putative transposases and simultaneous down
      regulation of genes coding for ribosomal protein synthesis, transport-related
      genes, non-coding RNA genes and metabolic genes. As yet we still do not know the
      role of several unknown genes and genes coding for hypothetical proteins which
      are either up- or down-regulated in LSP cells compared to SP cells. 

PMID- 24858918
TI  - Evaluation of schistosome promoter expression for transgenesis and genetic
      analysis.
AB  - Schistosome worms of the genus Schistosoma are the causative agents of
      schistosomiasis, a devastating parasitic disease affecting more than 240 million
      people worldwide. Schistosomes have complex life cycles, and have been
      challenging to manipulate genetically due to the dearth of molecular tools.
      Although the use of gene overexpression, gene knockouts or knockdowns are
      straight-forward genetic tools applied in many model systems, gene misexpression
      and genetic manipulation of schistosome genes in vivo has been exceptionally
      challenging, and plasmid based transfection inducing gene expression is limited.
      We recently reported the use of polyethyleneimine (PEI) as a simple and effective
      method for schistosome transfection and gene expression. Here, we use PEI
      mediated schistosome plasmid transgenesis to define and compare gene expression
      profiles from endogenous and nonendogenous promoters in the schistosomula stage
      of schistosomes that are potentially useful to misexpress (underexpress or
      overexpress) gene product levels. In addition, we overexpress schistosome genes
      in vivo using a strong promoter and show plasmid-based misregulation of genes in
      schistosomes, producing a clear and distinct phenotype--death. These data focus
      on the schistosomula stage, but they foreshadow strong potential for genetic
      characterization of schistosome molecular pathways, and potential for use in
      overexpression screens and drug resistance studies in schistosomes using plasmid
      based gene expression.

PMID- 24858922
TI  - Amoebicidal efficacy of a novel multi-purpose disinfecting solution: first
      findings.
AB  - Free-living amoebae of the genus Acanthamoeba can cause a sight-threatening
      corneal infection, Acanthamoeba keratitis, mostly in contact lens wearers. The
      use of ineffective contact lens disinfecting solutions is one of the most
      important risk factors for this infection. This study concerns a new multi
      purpose contact lens disinfecting solution, OPTI-FREE(r) PureMoist(r), tested for
      its efficacy against Acanthamoeba trophozoites and cysts by using the most
      probable number technique for amoebic enumeration. Acanthamoeba castellanii ATCC
      50373 and an environmental strain of Acanthamoeba genotype T4 isolated from tap
      water in Istanbul were used during the experiments. OPTI-FREE(r) PureMoist(r)
      achieved total kill (more than a 3-log reduction) of trophozoites of both strains
      before the manufacturer-recommended disinfection time (6h). In contrast, this
      solution had limited cysticidal activity against the ATCC strain but more against
      the environmental strain, with log reductions of 0.75 and 2.20, respectively,
      after 6h of exposure. 

PMID- 24858921
TI  - Tafazzin protein expression is associated with tumorigenesis and radiation
      response in rectal cancer: a study of Swedish clinical trial on preoperative
      radiotherapy.
AB  - BACKGROUND: Tafazzin (TAZ), a transmembrane protein contributes in mitochondrial
      structural and functional modifications through cardiolipin remodeling. TAZ
      mutations are associated with several diseases, but studies on the role of TAZ
      protein in carcinogenesis and radiotherapy (RT) response is lacking. Therefore we
      investigated the TAZ expression in rectal cancer, and its correlation with RT,
      clinicopathological and biological variables in the patients participating in a
      clinical trial of preoperative RT. METHODS: 140 rectal cancer patients were
      included in this study, of which 65 received RT before surgery and the rest
      underwent surgery alone. TAZ expression was determined by immunohistochemistry in
      primary cancer, distant, adjacent normal mucosa and lymph node metastasis. In
      silico protein-protein interaction analysis was performed to study the predictive
      functional interaction of TAZ with other oncoproteins. RESULTS: TAZ showed
      stronger expression in primary cancer and lymph node metastasis compared to
      distant or adjacent normal mucosa in both non-RT and RT patients. Strong TAZ
      expression was significantly higher in stages I-III and non-mucinious cancer of
      non-RT patients. In RT patients, strong TAZ expression in biopsy was related to
      distant recurrence, independent of gender, age, stages and grade (p = 0.043, HR,
      6.160, 95% CI, 1.063-35.704). In silico protein-protein interaction study
      demonstrated that TAZ was positively related to oncoproteins, Livin, MAC30 and
      FXYD-3. CONCLUSIONS: Strong expression of TAZ protein seems to be related to
      rectal cancer development and RT response, it can be a predictive biomarker of
      distant recurrence in patients with preoperative RT.

PMID- 24858923
TI  - Balamuthia mandrillaris in South America: an emerging potential hidden pathogen
      in Peru.
AB  - Balamuthia mandrillaris is a free living amoeba that can be isolated from soil.
      It is an emerging pathogen causing skin lesions as well as CNS involvement with a
      fatal outcome if untreated. Further, infections can sometimes can also appear in
      peripheral areas such as extremities (usually knee), or trunk. Moreover, it often
      progresses to an infiltrative lesion that occasionally becomes ulcerated. In
      countries like Peru, a skin lesion will precede other symptoms. This primary
      cutaneous lesion can be present for weeks or even months. However, the appearance
      of neurological disease predicts a poor prognosis. Diagnosis requires a high
      level of suspicion. 

PMID- 24858924
TI  - The phosphoglycerate kinase isoenzymes have distinct roles in the regulation of
      carbohydrate metabolism in Trypanosoma cruzi.
AB  - The glycolytic enzyme phosphoglycerate kinase (PGK) is present in Trypanosoma
      cruzi as three isoenzymes, two of them located inside glycosomes (PGKA and PGKC)
      and another one in the cytosol (PGKB). The three isoenzymes are expressed at all
      stages of the life cycle of the parasite. A heterologous expression system for
      PGKA (rPGKA) was developed and the substrate affinities of the natural and
      recombinant PGKA isoenzyme were determined. Km values measured for 3
      phosphoglycerate (3PGA) were 174 and 850 MUM, and for ATP 217 and 236 MUM, for
      the natural and recombinant enzyme, respectively. No significant differences were
      found between the two forms of the enzyme. The rPGKA was inhibited by Suramin
      with Ki values of 10.08 MUM and 12.11 MUM for ATP and 3PGA, respectively, and the
      natural enzyme was inhibited at similar values. A site-directed mutant was
      created in which the 80 amino acids PGKA sequence, present as a distinctive
      insertion in the N-terminal domain, was deleted. This internally truncated PGKA
      showed the same Km values and specific activity as the full-length rPGKA. The
      natural PGKC isoenzyme was purified from epimastigotes and separated from PGKA
      through molecular exclusion chromatography and its kinetic characteristics were
      determined. The Km value obtained for 3PGA was 192 MUM, and 10 MUM for ATP.
      Contrary to PGKA, the activity of PGKC is tightly regulated by ATP (substrate
      inhibition) with a Ki of 270 MUM, suggesting a role for this isoenzyme in
      regulating metabolic fluxes inside the glycosomes.

PMID- 24858925
TI  - Protein profiles and immunoreactivities of Acanthamoeba morphological groups and
      genotypes.
AB  - Acanthamoeba is a free-living protozoan found in a wide variety of habitats. A
      classification of Acanthamoeba into currently eighteen genotypes (T1-T18) has
      been established, however, data on differences between genotypes on the protein
      level are scarce. The aim of this study was to compare protein and
      immunoreactivity profiles of Acanthamoeba genotypes. Thirteen strains, both
      clinical and non-clinical, from genotypes T4, T5, T6, T7, T9, T11 and T12,
      representing three morphological groups, were investigated for their protein
      profiles and IgG, IgM and IgA immunoreactivities. It was shown that protein and
      immunoreactivity profiles of Acanthamoeba genotypes T4, T5, T6, T7, T9, T11 and
      T12 are clearly distinct from each other, but the banding patterns correlate to
      the morphological groups. Normal human sera revealed anti-Acanthamoeba antibodies
      against isolates of all investigated genotypes, interestingly, however only very
      weak IgM and virtually no IgA immunoreactivity with T7 and T9, both representing
      morphological group I. The strongest IgG, IgM and IgA immunoreactivities were
      observed for genotypes T4, T5 and T6. Differences of both, protein and
      immunological patterns, between cytopathic and non-cytopathic strains,
      particularly within genotype T4, were not at the level of banding patterns, but
      rather in expression levels. 

PMID- 24858926
TI  - Genotypic heterogeneity based on 18S-rRNA gene sequences among Acanthamoeba
      isolates from clinical samples in Italy.
AB  - Acanthamoeba keratitis (AK) is an ocular disease caused by members of a genus of
      free-living amoebae and it is associated predominantly with contact lens (CL)
      use. This study reports 55 cases of AK diagnosed in Italy. Genotype
      identification was carried out by PCR assay followed by sequence analysis of the
      18S rRNA gene using the genus specific primers JDP1 and JDP2. Genotype assignment
      was based on phenetic analysis of the ASA.S1 subset of the small-subunit rRNA
      gene sequences. The material has been collected at the Polyclinic Tor Vergata of
      Rome for a total of 19 isolates and at the Polyclinic Hospital of Bari (36
      isolates). Thirty-three out of the 55 genetically characterized isolates were
      assigned to the genotype T4. Ten isolates were identified as belonging to the
      genotype T15 thus confirming the first association between the genotype T15 and
      human amoebic keratitis previously described from the same area. We underline the
      occurrence of the genotype T3 and T11 identified for the first time in the
      country. 

PMID- 24858927
TI  - Examining the association between social health insurance participation and
      patients' out-of-pocket payments in China: the role of institutional arrangement.
AB  - Previous work on the relationship between social health insurance (SHI)
      participation and patients' out-of-pocket payments (OOP) in China has overlooked
      the mediating mechanisms of the institutional arrangement. This study establishes
      a conceptual framework involving the reimbursement, behavior management and
      purchasing mechanisms to elaborate on the institutional arrangement of SHI in
      China. Using structural equation modeling, data on 1645 hospitalized patients
      obtained from a nationally representative survey in China are analyzed. The
      results show that the behavior management and purchasing mechanisms of SHI
      perform poorly, undermining the function of the reimbursement mechanism and
      mitigating the association between SHI participation and OOP. As a result, SHI
      participation has a weak negative or even no significant association with the OOP
      of hospitalized patients. This seems to contradict the principles of SHI, which
      aims to reduce people's OOP and enhance their wellbeing. These findings are
      expected to provide valuable insights to the ongoing healthcare reform process in
      China. 

PMID- 24858928
TI  - Public acceptability of population-level interventions to reduce alcohol
      consumption: a discrete choice experiment.
AB  - Public acceptability influences policy action, but the most acceptable policies
      are not always the most effective. This discrete choice experiment provides a
      novel investigation of the acceptability of different interventions to reduce
      alcohol consumption and the effect of information on expected effectiveness,
      using a UK general population sample of 1202 adults. Policy options included
      high, medium and low intensity versions of: Minimum Unit Pricing (MUP) for
      alcohol; reducing numbers of alcohol retail outlets; and regulating alcohol
      advertising. Outcomes of interventions were predicted for: alcohol-related
      crimes; alcohol-related hospital admissions; and heavy drinkers. First, the
      models obtained were used to predict preferences if expected outcomes of
      interventions were not taken into account. In such models around half of
      participants or more were predicted to prefer the status quo over implementing
      outlet reductions or higher intensity MUP. Second, preferences were predicted
      when information on expected outcomes was considered, with most participants now
      choosing any given intervention over the status quo. Acceptability of MUP
      interventions increased by the greatest extent: from 43% to 63% preferring MUP of
      L1 to the status quo. Respondents' own drinking behaviour also influenced
      preferences, with around 90% of non-drinkers being predicted to choose all
      interventions over the status quo, and with more moderate than heavy drinkers
      favouring a given policy over the status quo. Importantly, the study findings
      suggest public acceptability of alcohol interventions is dependent on both the
      nature of the policy and its expected effectiveness. Policy-makers struggling to
      mobilise support for hitherto unpopular but promising policies should consider
      giving greater prominence to their expected outcomes.

PMID- 24858929
TI  - Icariside II improves cerebral microcirculatory disturbance and alleviates
      hippocampal injury in gerbils after ischemia-reperfusion.
AB  - OBJECTIVE: the purpose of the present study was to examine the protective effect
      of Icariside II (IS) on cerebral microcirculatory disturbance and neuronal injury
      in hippocampal CA1 region induced by global cerebral I/R and the underlying
      mechanism. METHODS: male Mongolian gerbils (50-70 g) were subjected to bilateral
      common carotid arteries occlusion for 30 min and followed by reperfusion for 72
      h. IS (20 mg/kg) was administered orally 2 h before ischemia and 6, 24, 48, 70 h
      after reperfusion. After 72 h of reperfusion, the leukocyte adhesion, albumin
      leakage, and velocity of RBC in the venules were determined with an upright
      microscope. Neuronal injury in hippocampal CA1 region was assessed by Nissl
      staining and the in situ TUNEL assay. Bax, Bcl-2, and cleaved caspase-3 proteins
      were detected by Western blot, and MDA content and complex I activity by ELISA
      assay in hippocampus. RESULTS: IS inhibited I/R-elicited leukocyte adhesion,
      albumin leakage and increased the velocity of RBC in cerebral venules. IS down
      regulated Bax and cleaved caspase-3 expression, up-regulated Bcl-2 expression of
      hippocampus and decreased the number of TUNEL positive neurons and the neuronal
      loss induced by I/R in hippocampal CA1 region. In addition, IS could increase the
      activity of complex I and decrease the production of MDA after I/R. CONCLUSIONS:
      IS could alleviate the microcirculatory disturbance and neuronal injury in
      hippocampal CA1 region induced by global cerebral I/R, which might involve
      regulating complex I activity.

PMID- 24858931
TI  - Urinary neopterin: an immune activation marker in mesangial proliferative
      glomerulonephritis.
AB  - BACKGROUND: To clarify in vivo neopterin expression within the human kidney and
      its clinical role as a biomarker for immune complex-mediated mesangial
      proliferative glomerulonephritis (mesPGN) in children. METHODS: We examined
      neopterin expression within the kidneys of 14 patients with mesPGN and five
      patients with minimal changes. We also measured the serum and urinary neopterin
      levels in fourteen patients with mesPGN and sixteen age-matched healthy controls
      and correlated the histological findings and clinical features. RESULTS:
      Neopterin expression was observed within the distal tubular epithelial cells. It
      was induced within the glomerular endothelial cells and infiltrated CD68-positive
      macrophages in the glomeruli and interstitial areas. Furthermore, urinary
      neopterin levels were significantly elevated and positively correlated with
      histopathological findings and the degree of proteinuria. CONCLUSIONS: These
      findings indicate that increased urinary neopterin may reflect macrophage
      activation and active inflammation within the kidney in immune complex-mediated
      glomerulonephritis. Neopterin may thus represent a useful biomarker of immune
      complex-mediated glomerulonephritis in the clinical setting.

PMID- 24858932
TI  - Glycoengineering of interferon-beta 1a improves its biophysical and
      pharmacokinetic properties.
AB  - The purpose of this study was to develop a biobetter version of recombinant human
      interferon-beta 1a (rhIFN-beta 1a) to improve its biophysical properties, such as
      aggregation, production and stability, and pharmacokinetic properties without
      jeopardizing its activity. To achieve this, we introduced additional
      glycosylation into rhIFN-beta 1a via site-directed mutagenesis. Glycoengineering
      of rhIFN-beta 1a resulted in a new molecular entity, termed R27T, which was
      defined as a rhIFN-beta mutein with two N-glycosylation sites at 80th (original
      site) and at an additional 25th amino acid due to a mutation of Thr for Arg at
      position 27th of rhIFN-beta 1a. Glycoengineering had no effect on rhIFN-beta
      ligand-receptor binding, as no loss of specific activity was observed. R27T
      showed improved stability and had a reduced propensity for aggregation and an
      increased half-life. Therefore, hyperglycosylated rhIFN-beta could be a biobetter
      version of rhIFN-beta 1a with a potential for use as a drug against multiple
      sclerosis. 

PMID- 24858934
TI  - Carotene Hydroxylase Activity Determines the Levels of Both alpha-Carotene and
      Total Carotenoids in Orange Carrots.
AB  - The typically intense carotenoid accumulation in cultivated orange-rooted carrots
      (Daucus carota) is determined by a high protein abundance of the rate-limiting
      enzyme for carotenoid biosynthesis, phytoene synthase (PSY), as compared with
      white-rooted cultivars. However, in contrast to other carotenoid accumulating
      systems, orange carrots are characterized by unusually high levels of alpha
      carotene in addition to beta-carotene. We found similarly increased alpha
      carotene levels in leaves of orange carrots compared with white-rooted cultivars.
      This has also been observed in the Arabidopsis thaliana lut5 mutant carrying a
      defective carotene hydroxylase CYP97A3 gene. In fact, overexpression of CYP97A3
      in orange carrots restored leaf carotenoid patterns almost to those found in
      white-rooted cultivars and strongly reduced alpha-carotene levels in the roots.
      Unexpectedly, this was accompanied by a 30 to 50% reduction in total root
      carotenoids and correlated with reduced PSY protein levels while PSY expression
      was unchanged. This suggests a negative feedback emerging from carotenoid
      metabolites determining PSY protein levels and, thus, total carotenoid flux.
      Furthermore, we identified a deficient CYP97A3 allele containing a frame-shift
      insertion in orange carrots. Association mapping analysis using a large carrot
      population revealed a significant association of this polymorphism with both
      alpha-carotene content and the alpha-/beta-carotene ratio and explained a large
      proportion of the observed variation in carrots.

PMID- 24858930
TI  - Mesenchymal stem cells as cellular vectors for pediatric neurological disorders.
AB  - Lysosomal storage diseases are a heterogeneous group of hereditary disorders
      characterized by a deficiency in lysosomal function. Although these disorders
      differ in their etiology and phenotype those that affect the nervous system
      generally manifest as a profound deterioration in neurologic function with age.
      Over the past several decades implementation of various treatment regimens
      including bone marrow and cord blood cell transplantation, enzyme replacement,
      and substrate reduction therapy have proved effective for managing some clinical
      manifestations of these diseases but their ability to ameliorate neurologic
      complications remains unclear. Consequently, there exists a need to develop
      alternative therapies that more effectively target the central nervous system.
      Recently, direct intracranial transplantation of tissue-specific stem and
      progenitor cells has been explored as a means to reconstitute metabolic
      deficiencies in the CNS. In this chapter we discuss the merits of bone marrow
      derived mesenchymal stem cells (MSCs) for this purpose. Originally identified as
      progenitors of connective tissue cell lineages, recent findings have revealed
      several novel aspects of MSC biology that make them attractive as therapeutic
      agents in the CNS. We relate these advances in MSC biology to their utility as
      cellular vectors for treating neurologic sequelae associated with pediatric
      neurologic disorders. 

PMID- 24858935
TI  - SAUR Inhibition of PP2C-D Phosphatases Activates Plasma Membrane H+-ATPases to
      Promote Cell Expansion in Arabidopsis.
AB  - The plant hormone auxin promotes cell expansion. Forty years ago, the acid growth
      theory was proposed, whereby auxin promotes proton efflux to acidify the apoplast
      and facilitate the uptake of solutes and water to drive plant cell expansion.
      However, the underlying molecular and genetic bases of this process remain
      unclear. We have previously shown that the SAUR19-24 subfamily of auxin-induced
      SMALL AUXIN UP-RNA (SAUR) genes promotes cell expansion. Here, we demonstrate
      that SAUR proteins provide a mechanistic link between auxin and plasma membrane
      H+-ATPases (PM H+-ATPases) in Arabidopsis thaliana. Plants overexpressing
      stabilized SAUR19 fusion proteins exhibit increased PM H+-ATPase activity, and
      the increased growth phenotypes conferred by SAUR19 overexpression are dependent
      upon normal PM H+-ATPase function. We find that SAUR19 stimulates PM H+-ATPase
      activity by promoting phosphorylation of the C-terminal autoinhibitory domain.
      Additionally, we identify a regulatory mechanism by which SAUR19 modulates PM H+
      ATPase phosphorylation status. SAUR19 as well as additional SAUR proteins
      interact with the PP2C-D subfamily of type 2C protein phosphatases. We
      demonstrate that these phosphatases are inhibited upon SAUR binding, act
      antagonistically to SAURs in vivo, can physically interact with PM H+-ATPases,
      and negatively regulate PM H+-ATPase activity. Our findings provide a molecular
      framework for elucidating auxin-mediated control of plant cell expansion.

PMID- 24858936
TI  - PHYTOCHROME INTERACTING FACTOR1 Enhances the E3 Ligase Activity of CONSTITUTIVE
      PHOTOMORPHOGENIC1 to Synergistically Repress Photomorphogenesis in Arabidopsis.
AB  - CONSTITUTIVE PHOTOMORPHOGENIC1 (COP1) is a RING/WD40 repeat-containing ubiquitin
      E3 ligase that is conserved from plants to humans. COP1 forms complexes with
      SUPPRESSOR OF PHYTOCHROME A (SPA) proteins, and these complexes degrade
      positively acting transcription factors in the dark to repress
      photomorphogenesis. Phytochrome-interacting basic helix-loop-helix transcription
      factors (PIFs) also repress photomorphogenesis in the dark. In response to light,
      the phytochrome family of sensory photoreceptors simultaneously inactivates COP1
      SPA complexes and induces the rapid degradation of PIFs to promote
      photomorphogenesis. However, the functional relationship between PIFs and COP1
      SPA complexes is still unknown. Here, we present genetic evidence that the pif
      and cop1/spa Arabidopsis thaliana mutants synergistically promote
      photomorphogenesis in the dark. LONG HYPOCOTYL5 (HY5) is stabilized in the cop1
      pif1, spa123 pif1, and pif double, triple, and quadruple mutants in the dark.
      Moreover, the hy5 mutant suppresses the constitutive photomorphogenic phenotypes
      of the pifq mutant in the dark. PIF1 forms complexes with COP1, HY5, and SPA1 and
      enhances the substrate recruitment and autoubiquitylation and transubiquitylation
      activities of COP1. These data uncover a novel function of PIFs as the potential
      cofactors of COP1 and provide a genetic and biochemical model of how PIFs and
      COP1-SPA complexes synergistically repress photomorphogenesis in the dark.

PMID- 24858939
TI  - Francois Jacob: the Mensch behind the scientist.

PMID- 24858938
TI  - Ocimum sanctum (L.) essential oil and its lead molecules induce apoptosis in
      Candida albicans.
AB  - Manipulation of endogenous responses during programmed cell death (PCD) in fungi
      can lead to development of effective therapeutic strategies. In the present
      study, we evaluated the physiology of cell death in Candida albicans in response
      to Ocimum sanctum essential oil (OSEO) and its two major constituents - methyl
      chavicol (MET CHAV) and linalool (LIN) at varying inhibitory concentrations.
      Apoptotic cell death was studied on the basis of externalization of membrane
      phosphatidylserine (PS) revealed by annexin-V-FITC labeling, morphological
      alterations revealed by transmission electron microscopy and DNA fragmentation by
      terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)
      assay. Exposure of fungal cells to MIC/4 of OSEO, MET CHAV and LIN resulted in
      morphological features characteristic of apoptosis, while necrosis was observed
      at higher concentrations. Necrotic cells displayed reduced TUNEL staining and an
      inability to exclude propidium iodide. In addition, they lacked a defined nucleus
      and an intact external morphology. Exposed cells were TUNEL-positive, showed
      chromatin condensation and margination, nuclear envelope separation, nuclear
      fragmentation, cytoplasmic shrinkage and plasma membrane blebbing. A dose
      dependent decrease in cytochrome c oxidase activity was observed with each
      compound, but the decrease was not comparable to that elicited by H2O2,
      eliminating the primary involvement of cytochrome c release in apoptosis thus
      induced. Previously reported data revealed induction of apoptosis at low
      concentrations as a result of oxidative insult. Studies aimed at identifying
      other mitochondrial factors activated during this course to mediate apoptosis
      will further elucidate the mechanism of antifungal action of these natural
      products. 

PMID- 24858937
TI  - A Zinc Finger Protein Regulates Flowering Time and Abiotic Stress Tolerance in
      Chrysanthemum by Modulating Gibberellin Biosynthesis.
AB  - Flowering time and an ability to tolerate abiotic stresses are important for
      plant growth and development. We characterized BBX24, a zinc finger transcription
      factor gene, from Chrysanthemum morifolium and found it to be associated with
      both flowering time and stress tolerance. Transgenic lines with suppressed
      expression of Cm-BBX24 (Cm-BBX24-RNAi) flowered earlier than wild-type plants and
      showed decreased tolerance to freezing and drought stresses. Global expression
      analysis revealed that genes associated with both photoperiod and gibberellin
      (GA) biosynthesis pathways were upregulated in Cm-BBX24-RNAi lines, relative to
      the wild type. By contrast, genes that were upregulated in overexpressing lines
      (Cm-BBX24-OX), but downregulated in Cm-BBX24-RNAi lines (both relative to the
      wild type), included genes related to compatible solutes and carbohydrate
      metabolism, both of which are associated with abiotic stress. Cm-BBX24 expression
      was also influenced by daylength and GA4/7 application. Under long days, changes
      in endogenous GA1, GA4, GA19, and GA20 levels occurred in young leaves of
      transgenic lines, relative to the wild type. Regulation of flowering involves the
      FLOWERING TIME gene, which integrates photoperiod and GA biosynthesis pathways.
      We postulate that Cm-BBX24 plays a dual role, modulating both flowering time and
      abiotic stress tolerance in chrysanthemum, at least in part by influencing GA
      biosynthesis.

PMID- 24858940
TI  - How Francois Jacob bridged the gap between the "two cultures".
AB  - While the scientific contributions of Francois Jacob were outstanding, I also
      consider that his conception of science, and of its place among other forms of
      knowledge, is also highly original, and important for the future of science in
      our societies. His contributions to the history and philosophy of science were
      neither a hobby nor a secondary activity, but they were for him a natural
      complement to his scientific work. He fully opposed the concept of the two
      cultures, the literary and the scientific, proposed by C.P. Snow. For Jacob,
      concepts, metaphors and models circulated between the various spheres of human
      activity. This is obvious in his own work. This "open" conception of scientific
      activity did not prevent him from defending the specificity, and the superiority,
      of scientific knowledge. 

PMID- 24858941
TI  - Fish oil supplementation decreases oxidative stress but does not affect platelet
      activating factor bioactivity in lungs of asthmatic rats.
AB  - Dietary fish oil supplementation increases the content of n-3 polyunsaturated
      fatty acids (PUFA) in cellular membranes. The highly unsaturated nature of n-3
      PUFA could result in an enhanced lipid peroxidation in the oxidative environment
      characteristic of asthma. The oxidative reaction cascade culminates in an
      increased production of components associated to oxidative stress and of an
      important proinflammatory mediator platelet-activating factor (PAF)-like lipid.
      We evaluated the effect of fish oil supplementation in asthmatic rats upon the
      PAF bioactivity and parameters related to oxidative stress in the lung. Fish oil
      supplementation of asthmatic rats resulted in lower concentrations of nitrite
      (1.719 +/- 0.137 vs. 2.454 +/- 0.163 nmol/mL) and lipid hydroperoxide (72.190 +/-
      7.327 vs. 120.200 +/- 11.270 nmol/mg protein). In asthmatic animals, fish oil
      increased the activities of superoxide dismutase (EC 1.15.1.1) (33.910 +/- 2.325
      vs. 24.110 +/- 0.618 U/mg protein) and glutathione peroxidase (EC 1.11.1.9)
      (164.100 +/- 31.250 vs. 12.590 +/- 5.234 U/mg protein). However, fish oil did not
      affect PAF bioactivity in lung tissue of asthmatic rats (0.545 +/- 0.098 340/380
      vs. 0.669 +/- 0.101 340/380 nm ratio). Considering the two-step process-
      oxidative stress and PAF bioactivity--fish oil exhibited a divergent action on
      these aspects of asthmatic inflammation, since the supplement lowered oxidative
      stress in the lungs of asthmatic rats, presenting an antioxidant effect, but did
      not affect PAF bioactivity. This suggests a dual effect of fish oil on oxidative
      stress and inflammation in asthma.

PMID- 24858942
TI  - A prospective matched case-control study of laparoendoscopic single-site vs
      conventional laparoscopic myomectomy.
AB  - STUDY OBJECTIVE: To compare operative and obstetric outcomes of laparoendoscopic
      single-site myomectomy (LESS-M) vs conventional laparoscopic myomectomy (LM).
      DESIGN: Prospective matched case-control study. SETTING: A university hospital
      and a tertiary care center. PATIENTS: Forty-five women underwent LESS-M, and 90
      women underwent conventional LM. INTERVENTION: LESS-M or conventional LM.
      MEASUREMENTS AND MAIN RESULTS: Operative and obstetric outcomes. There were no
      significant differences between the 2 groups in demographic characteristics,
      operative time (135 vs 140 minutes), change in hemoglobin concentration (1.9 vs
      1.95 g/dL), return of bowel activity (35 vs 28 hours), hospital stay (5 vs 5
      days), or complication rate (11.1% vs 8.9%). Insofar as obstetric outcomes, no
      significant differences were observed between the 2 groups for duration of follow
      up (24.4 vs 23.2 months), pregnancy rate in patients who desired pregnancy (66.7%
      vs 50.0%), full-term delivery rate (66.7% vs 58.3%), and time to first pregnancy
      after surgery (7.6 vs 10.1 months). CONCLUSION: LESS-M is feasible and safe and
      has comparable obstetric outcomes to conventional LM in selected women with
      symptomatic myomas. However, a large prospective randomized study is needed.

PMID- 24858943
TI  - Surgical and clinical impact of extraserosal pelvic fascia removal in segmental
      colorectal resection for endometriosis.
AB  - STUDY OBJECTIVE: To describe the characteristics of patients with colorectal
      endometriosis and extraserosal pelvic fascia (EPF) involvement and to assess the
      effect of EPF resection. DESIGN: Prospective cohort study (Canadian Task Force
      classification II-2). SETTING: University hospital. PATIENTS: Two hundred twenty
      seven patients who underwent segmental colorectal resection to treat symptomatic
      deep infiltrating endometriosis between 2001 and 2011, with or without EPF
      resection. INTERVENTIONS: Segmental colorectal resection with or without EPF
      resection. MEASUREMENTS AND MAIN RESULTS: One hundred twelve patients (49.4%)
      required EPF resection. In these patients the total American Society for
      Reproductive Medicine endometriosis scores were higher (p = .004), there were
      more associated resected lesions of deep infiltrating endometriosis (p <.001),
      and the operative time was longer (p <.001). They were more likely to require
      blood transfusion (p = .003) and to experience intraoperative complications (p =
      .01) and postoperative voiding dysfunction (p = .04). CONCLUSION: EPF
      infiltration reflects disease severity in patients with colorectal endometriosis.
      Its removal affects intraoperative morbidity and leads to a higher rate of
      voiding dysfunction.

PMID- 24858944
TI  - TLR4 inhibitor resatorvid provides neuroprotection in experimental traumatic
      brain injury: implication in the treatment of human brain injury.
AB  - Toll-like receptor 4 (TLR4) is considered to play an important role in neuronal
      death in animal models and could be an important therapeutic target following
      traumatic brain injury (TBI). Resatorvid is a small molecule, commonly accepted
      to inhibit TLR4-mediated pathway. The purpose of this study was to investigate
      the neuroprotective effect of resatorvid after TBI. Our data revealed that
      inhibition of TLR4 by resatorvid attenuated the development of TBI in mouse
      model. And we found that resatorvid administration dramatically reduced neuronal
      apoptosis. To investigate the cellular mechanism, we evaluated the expression of
      transforming growth factor-beta-activated kinase 1 (TAK1), which plays a crucial
      role in TLR4 signal transduction pathway and is activated by phosphorylation in
      response to TBI. In addition, enzyme-linked immunosorbent assay was used to
      determine the expression of tumor necrosis factor-alpha (TNF-alpha) and
      interlukin-1beta (IL-1beta) at 24h after injury. Our results showed that
      resatorvid treatment significantly reduced the protein levels of TAK1, p-TAK1,
      TNF-alpha, and IL-1beta compared with vehicle treatment. Importantly, the delayed
      therapy (4h post injury) once daily consecutively for 5days ameliorated brain
      damage and improved neurological recovery, suggesting that this drug has a wide
      therapeutic time window. Clinically, we observed that TLR4 and TAK1 expression
      was significantly increased in human contusion specimens after TBI. These data
      provide an experimental rationale for the evaluation of TLR4 as a clinical target
      and therapeutic implication of resatorvid in human traumatic brain injury. 

PMID- 24858945
TI  - Galphai2- and Galphai3-deficient mice display opposite severity of myocardial
      ischemia reperfusion injury.
AB  - G-protein-coupled receptors (GPCRs) are the most abundant receptors in the heart
      and therefore are common targets for cardiovascular therapeutics. The activated
      GPCRs transduce their signals via heterotrimeric G-proteins. The four major
      families of G-proteins identified so far are specified through their alpha
      subunit: Galphai, Galphas, Galphaq and G12/13. Galphai-proteins have been
      reported to protect hearts from ischemia reperfusion injury. However, determining
      the individual impact of Galphai2 or Galphai3 on myocardial ischemia injury has
      not been clarified yet. Here, we first investigated expression of Galphai2 and
      Galphai3 on transcriptional level by quantitative PCR and on protein level by
      immunoblot analysis as well as by immunofluorescence in cardiac tissues of wild
      type, Galphai2-, and Galphai3-deficient mice. Galphai2 was expressed at higher
      levels than Galphai3 in murine hearts, and irrespective of the isoform being
      knocked out we observed an up regulation of the remaining Galphai-protein.
      Myocardial ischemia promptly regulated cardiac mRNA and with a slight delay
      protein levels of both Galphai2 and Galphai3, indicating important roles for both
      Galphai isoforms. Furthermore, ischemia reperfusion injury in Galphai2- and
      Galphai3-deficient mice exhibited opposite outcomes. Whereas the absence of
      Galphai2 significantly increased the infarct size in the heart, the absence of
      Galphai3 or the concomitant upregulation of Galphai2 dramatically reduced cardiac
      infarction. In conclusion, we demonstrate for the first time that the genetic
      ablation of Galphai proteins has protective or deleterious effects on cardiac
      ischemia reperfusion injury depending on the isoform being absent. 

PMID- 24858946
TI  - Inhibition of protein tyrosine phosphatases enhances cerebral collateral growth
      in rats.
AB  - Arteriogenesis involves the rapid proliferation of preexisting arterioles to
      fully functional arteries as a compensatory mechanism to overcome circulatory
      deficits. Stimulation of arteriogenesis has therefore been considered a treatment
      concept in arterial occlusive disease. Here, we investigated the impact of
      inhibition of protein tyrosine phosphatases (PTPs) on cerebral arteriogenesis in
      rats. Arteriogenesis was induced by occlusion of one carotid and both vertebral
      arteries (three-vessel occlusion (3-VO)). Collateral growth and functional vessel
      perfusion was assessed 3-35 days following 3-VO. Furthermore, animals underwent 3
      VO surgery and were treated with the pan-PTP inhibitor BMOV, the SHP-1 inhibitor
      sodium stibogluconate (SSG), or the PTP1B inhibitor AS279. Cerebral vessel
      diameters and cerebrovascular reserve capacity (CVRC) were determined, together
      with immunohistochemistry analyses and proximity ligation assays (PLA) for
      determination of tissue proliferation and phosphorylation patterns after 7 days.
      The most significant changes in vessel diameter increase were present in the
      ipsilateral posterior cerebral artery (PCA), with proliferative markers (PCNA)
      being time-dependently increased. The CVRC was lost in the early phase after 3-VO
      and partially recovered after 21 days. PTP inhibition resulted in a significant
      increase in the ipsilateral PCA diameter in BMOV-treated animals and rats
      subjected to PTP1B inhibition. Furthermore, CVRC was significantly elevated in
      AS279-treated rats compared to control animals, along with hyperphosphorylation
      of the platelet-derived growth factor-beta receptor in the vascular wall in vivo.
      In summary, our data indicate PTPs as hitherto unrecognized negative regulators
      in cerebral arteriogenesis. Further, PTP inhibition leading to enhanced
      collateral growth and blood perfusion suggests PTPs as novel targets in anti
      ischemic treatment. KEY MESSAGES: PTPs exhibit negative regulatory function in
      cerebral collateral growth in rats. Inhibition of pan-PTP/PTP1B increases vessel
      PDGF-beta receptor phosphorylation. PTP1B inhibition enhances arteriogenesis and
      cerebrovascular reserve capacity.

PMID- 24858947
TI  - The hepatoselective glucokinase activator PF-04991532 ameliorates hyperglycemia
      without causing hepatic steatosis in diabetic rats.
AB  - Hyperglycemia resulting from type 2 diabetes mellitus (T2DM) is the main cause of
      diabetic complications such as retinopathy and neuropathy. A reduction in
      hyperglycemia has been shown to prevent these associated complications supporting
      the importance of glucose control. Glucokinase converts glucose to glucose-6
      phosphate and determines glucose flux into the beta-cells and hepatocytes. Since
      activation of glucokinase in beta-cells is associated with increased risk of
      hypoglycemia, we hypothesized that selectively activating hepatic glucokinase
      would reduce fasting and postprandial glucose with minimal risk of hypoglycemia.
      Previous studies have shown that hepatic glucokinase overexpression is able to
      restore glucose homeostasis in diabetic models; however, these overexpression
      experiments have also revealed that excessive increases in hepatic glucokinase
      activity may also cause hepatosteatosis. Herein we sought to evaluate whether
      liver specific pharmacological activation of hepatic glucokinase is an effective
      strategy to reduce hyperglycemia without causing adverse hepatic lipids changes.
      To test this hypothesis, we evaluated a hepatoselective glucokinase activator, PF
      04991532, in Goto-Kakizaki rats. In these studies, PF-04991532 reduced plasma
      glucose concentrations independent of changes in insulin concentrations in a dose
      dependent manner both acutely and after 28 days of sub-chronic treatment. During
      a hyperglycemic clamp in Goto-Kakizaki rats, the glucose infusion rate was
      increased approximately 5-fold with PF-04991532. This increase in glucose
      infusion can be partially attributed to the 60% reduction in endogenous glucose
      production. While PF-04991532 induced dose-dependent increases in plasma
      triglyceride concentrations it had no effect on hepatic triglyceride
      concentrations in Goto-Kakizaki rats. Interestingly, PF-04991532 decreased
      intracellular AMP concentrations and increased hepatic futile cycling. These data
      suggest that hepatoselective glucokinase activation may offer glycemic control
      without inducing hepatic steatosis supporting the evaluation of tissue specific
      activators in clinical trials. 

PMID- 24858949
TI  - Endosidin 7 Specifically Arrests Late Cytokinesis and Inhibits Callose
      Biosynthesis, Revealing Distinct Trafficking Events during Cell Plate Maturation.
AB  - Although cytokinesis is vital for plant growth and development, our mechanistic
      understanding of the highly regulated membrane and cargo transport mechanisms in
      relation to polysaccharide deposition during this process is limited. Here, we
      present an in-depth characterization of the small molecule endosidin 7 (ES7)
      inhibiting callose synthase activity and arresting late cytokinesis both in vitro
      and in vivo in Arabidopsis (Arabidopsis thaliana). ES7 is a specific inhibitor
      for plant callose deposition during cytokinesis that does not affect endomembrane
      trafficking during interphase or cytoskeletal organization. The specificity of
      ES7 was demonstrated (1) by comparing its action with that of known inhibitors
      such as caffeine, flufenacet, and concanamycin A and (2) across kingdoms with a
      comparison in yeast. The interplay between cell plate-specific post-Golgi vesicle
      traffic and callose accumulation was analyzed using ES7, and it revealed unique
      and temporal contributions of secretory and endosomal vesicles in cell plate
      maturation. While RABA2A-labeled vesicles, which accumulate at the early stage of
      cell plate formation, were not affected by ES7, KNOLLE was differentially altered
      by the small molecule. In addition, the presence of clathrin-coated vesicles in
      cells containing elevated levels of callose and their reduction under ES7
      treatment further support the role of endocytic membrane remodeling in the
      maturing cell plate while the plate is stabilized by callose. Taken together,
      these data show the essential role of callose during the late stages of cell
      plate maturation and establish the temporal relationship between vesicles and
      regulatory proteins at the cell plate assembly matrix during polysaccharide
      deposition.

PMID- 24858950
TI  - The use of amphipols for NMR structural characterization of 7-TM proteins.
AB  - While amphipols have been proven useful for refolding of seven transmembrane
      helical (7-TM) proteins including G-protein-coupled receptors (GPCRs) and it
      could be shown that an amphipol environment is in principle suitable for NMR
      structural studies of the embedded protein, high-resolution NMR insights into
      amphipol refolded and isotopically labeled GPCRs are still very limited. Here we
      report on the recent progress toward NMR structural studies of the melanocortin-2
      and -4 receptors, two class A GPCRs which so far have not been reported to be
      incorporated into an amphipol environment. Making use of the established 7-TM
      protein bacteriorhodopsin (BR) we initially tested and optimized amphipol
      refolding conditions. Most promising conditions were transferred to the refolding
      of the two melanocortin receptors. Analytical-scale refolding experiments on the
      melanocortin-2 receptor show very similar behavior to the results obtained on BR.
      Using cell-free protein expression we could generate sufficient amounts of
      isotopically labeled bacteriorhodopsin as well as melanocortin-2 and -4 receptors
      for an initial NMR analysis. Upscaling of the amphipol refolding protocol to
      protein amounts needed for NMR structural studies was, however, not
      straightforward and impeded detailed NMR insights for the two GPCRs. While well
      resolved and dispersed NMR spectra could only be obtained for bacteriorhodopsin,
      a comparison of NMR data recorded on the melanocortin-4 receptor in SDS and in an
      amphipol environment indicates that amphipol refolding induces larger structural
      modifications in the receptor. 

PMID- 24858951
TI  - Niflumic acid affects store-operated Ca(2+)-permeable (SOC) and Ca (2+)-dependent
      K (+) and Cl (-) ion channels and induces apoptosis in K562 cells.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) are known to induce apoptosis in a
      variety of cancer cells. However, the precise mechanisms by which NSAIDs
      facilitate apoptosis in tumor cells are not clear. In the present study, we show
      that niflumic acid (NA), a member of the fenamates group of NSAIDs and Cl(-) and
      Ca(2+)-activated Cl(-) (CAC) channels blocker, induced apoptosis (by ~8 %, 24 h
      treatment) and potentiated (by 8-10 %) apoptotic effect of endoplasmic reticulum
      Ca(2+) mobilizer thapsigargin (Tg) in human erythroleukemic K562 cell line. The
      whole-cell patch clamp and Fluo-3 flow cytometric experiments confirmed an
      inhibitory effect of NA (100 and 300 uM) on store-operated (SOC) channels. We
      also found that NA-blocked CAC channels were activated by acute application of Tg
      (2 uM) in K562 cells. NA blockage of CAC channels was accompanied by activation
      of Ca(2+)-activated K(+) (SK4) channels. The observed effects of NA were not
      connected with COX-2 inhibition since 100-nM NA (IC50 for COX-2 inhibition) did
      not induce either apoptosis or affect the channels activity. We conclude that
      inhibition of SOC channels plays a major role in NA-induced apoptosis. Increased
      apoptotic levels in Tg-treated K562 cells in the presence of NA may be due to the
      blockage of CAC and stimulation of SK4 channels in addition to SOC channels
      inhibition.

PMID- 24858954
TI  - Photon irradiation response of photonic crystal fibres and flat fibres at
      radiation therapy doses.
AB  - Radiation effects of photon irradiation in pure Photonic Crystal Fibres (PCF) and
      Flat fibres (FF) are still much less investigated in thermoluminescense dosimetry
      (TLD). We have reported the TL response of PCF and FF subjected to 6 MV photon
      irradiation. The proposed dosimeter shows good linearity at doses ranging from 1
      to 4 Gy. The small size of these detectors points to its use as a dosimeter at
      megavoltage energies, where better tissue-equivalence and the Bragg-Gray cavity
      theory prevails.

PMID- 24858955
TI  - Cyclotron production and radiochemical purification of (88,89)Zr via alpha
      particle induced reactions on natural strontium.
AB  - The radionuclides (88)Zr and (89)Zr have been produced by cyclotron irradiation
      of (nat)SrO with 35 MeV alpha-particles at a beam current of 15 MUA. The thick
      source production yield of (89)Zr is ~3.1 MBq MUA(-1) h(-1). A two-step
      radiochemical purification utilising anion-exchange chromatography in
      hydrochloric and hydrofluoric acids has been developed to separate (88,89)Zr from
      the target material, natural strontium, the target substrate, aluminium, and long
      lived (88)Y.

PMID- 24858952
TI  - Metabolic implications when employing heavy pre- and post-exercise rapid-acting
      insulin reductions to prevent hypoglycaemia in type 1 diabetes patients: a
      randomised clinical trial.
AB  - AIM: To examine the metabolic, gluco-regulatory-hormonal and inflammatory
      cytokine responses to large reductions in rapid-acting insulin dose administered
      prandially before and after intensive running exercise in male type 1 diabetes
      patients. METHODS: This was a single centre, randomised, controlled open label
      study. Following preliminary testing, 8 male patients (24+/-2 years, HbA1c 7.7+/
      0.4%/61+/-4 mmol.l-1) treated with insulin's glargine and aspart, or lispro
      attended the laboratory on two mornings at ~08:00 h and consumed a standardised
      breakfast carbohydrate bolus (1 g carbohydrate.kg-1BM; 380+/-10 kcal) and self
      administered a 75% reduced rapid-acting insulin dose 60 minutes before 45 minutes
      of intensive treadmill running at 73.1+/-0.9% VO2peak. At 60 minutes post
      exercise, patients ingested a meal (1 g carbohydrate.kg-1BM; 660+/-21 kcal) and
      administered either a Full or 50% reduced rapid-acting insulin dose. Blood
      glucose and lactate, serum insulin, cortisol, non-esterified-fatty-acids, beta
      Hydroxybutyrate, and plasma glucagon, adrenaline, noradrenaline, IL-6, and TNF
      alpha concentrations were measured for 180 minutes post-meal. RESULTS: All
      participants were analysed. All glycaemic, metabolic, hormonal, and cytokine
      responses were similar between conditions up to 60 minutes following exercise.
      Following the post-exercise meal, serum insulin concentrations were lower under
      50% (p<0.05) resulting in 75% of patients experiencing hyperglycaemia (blood
      glucose >=8.0 mmol.l-1; 50% n = 6, Full n = 3). beta-Hydroxybutyrate
      concentrations decreased similarly, such that at 180 minutes post-meal
      concentrations were lower than rest under Full and 50%. IL-6 and TNF-alpha
      concentrations remained similar to fasting levels under 50% but declined under
      Full. Under 50% IL-6 concentrations were inversely related with serum insulin
      concentrations (r = -0.484, p = 0.017). CONCLUSIONS: Heavily reducing rapid
      acting insulin dose with a carbohydrate bolus before, and a meal after intensive
      running exercise may cause hyperglycaemia, but does not augment ketonaemia, raise
      inflammatory cytokines TNF-alpha and IL-6 above fasting levels, or cause other
      adverse metabolic or hormonal disturbances. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT01531855.

PMID- 24858956
TI  - Development of work participation in young adults with cerebral palsy: a
      longitudinal study.
AB  - OBJECTIVE: To document the development of work participation in young adults with
      cerebral palsy who are transitioning into adulthood, examine associated
      characteristics, and investigate work limitations and barriers among employed
      persons. DESIGN: Observational longitudinal cohort study. SUBJECTS: Seventy-four
      young adults with cerebral palsy of average intelligence, aged 16-20 years at
      baseline. METHODS: Work participation in 3 categories (employed, unemployed,
      studying) was assessed at baseline, 2-year and 4-year follow-ups using structured
      interviews. At 4-year follow-up, associations of work participation with
      demographic and clinical characteristics were examined using multinomial logistic
      regression. Work limitations and barriers among employed persons were evaluated
      using questionnaires. RESULTS: From age range 16-20 years to age range 20-24
      years the proportions of subjects who were employed and unemployed increased from
      12% to 49% and 3% to 17%, respectively; the proportion who were students
      decreased from 85% to 34%. In the age range 20-24 years, the employment rate of
      young adults with cerebral palsy was lower and the unemployment rate higher, than
      that of the general population. A lower level of gross motor function and younger
      age were associated with unemployment. Employed persons experienced few work
      limitations; 28% experienced situational or health barriers. CONCLUSION: Young
      adults with cerebral palsy and average intelligence are at risk of experiencing
      unfavourable developments in work participation. Rehabilitation services should
      offer support to prevent unemployment and occupational disability.

PMID- 24858958
TI  - Utility of syntenic relationships of VDAC1 pseudogenes for not only an
      understanding of the phylogenetic divergence history of rodents, but also
      ascertaining possible pseudogene candidates as genuine pseudogenes.
AB  - Rodent and human genomes were screened to identify pseudogenes of the type 1
      voltage-dependent anion channel (VDAC1) in mitochondria. In addition to the 16
      pseudogenes of rat VDAC1 identified in our recent study, 15 and 13 sequences were
      identified as pseudogenes of VDAC1 in mouse and human genome, respectively; and
      4, 2, and 1 sequences, showing lower similarities with the VDAC1 sequence, were
      identified as "possible pseudogene candidates" in rat, mouse, and human,
      respectively. No syntenic combination was observed between rodent and human
      pseudogenes, but 2 and 1 possible pseudogene candidates of VDAC1 of rat and
      mouse, respectively, were found to have syntenic counterparts in mouse and rat
      genome, respectively; and these syntenic counterparts were genuine VDAC1
      pseudogenes. Therefore, syntenic combinations of pseudogenes of VDAC1 were useful
      not only for a better understanding of the phylogenetic divergence history of
      rodents but also for ascertaining possible pseudogene candidates as genuine
      pseudogenes. 

PMID- 24858957
TI  - Theory of amorphous ices.
AB  - We derive a phase diagram for amorphous solids and liquid supercooled water and
      explain why the amorphous solids of water exist in several different forms.
      Application of large-deviation theory allows us to prepare such phases in
      computer simulations. Along with nonequilibrium transitions between the ergodic
      liquid and two distinct amorphous solids, we establish coexistence between these
      two amorphous solids. The phase diagram we predict includes a nonequilibrium
      triple point where two amorphous phases and the liquid coexist. Whereas the
      amorphous solids are long-lived and slowly aging glasses, their melting can lead
      quickly to the formation of crystalline ice. Further, melting of the higher
      density amorphous solid at low pressures takes place in steps, transitioning to
      the lower-density glass before accessing a nonequilibrium liquid from which ice
      coarsens. 

PMID- 24858960
TI  - Displacement parameter inversion for a novel electromagnetic underground
      displacement sensor.
AB  - Underground displacement monitoring is an effective method to explore deep into
      rock and soil masses for execution of subsurface displacement measurements. It is
      not only an important means of geological hazards prediction and forecasting, but
      also a forefront, hot and sophisticated subject in current geological disaster
      monitoring. In previous research, the authors had designed a novel
      electromagnetic underground horizontal displacement sensor (called the H-type
      sensor) by combining basic electromagnetic induction principles with modern
      sensing techniques and established a mutual voltage measurement theoretical model
      called the Equation-based Equivalent Loop Approach (EELA). Based on that work,
      this paper presents an underground displacement inversion approach named "EELA
      forward modeling-approximate inversion method". Combining the EELA forward
      simulation approach with the approximate optimization inversion theory, it can
      deduce the underground horizontal displacement through parameter inversion of the
      H-type sensor. Comprehensive and comparative studies have been conducted between
      the experimentally measured and theoretically inversed values of horizontal
      displacement under counterpart conditions. The results show when the measured
      horizontal displacements are in the 0-100 mm range, the horizontal displacement
      inversion discrepancy is generally tested to be less than 3 mm under varied tilt
      angles and initial axial distances conditions, which indicates that our proposed
      parameter inversion method can predict underground horizontal displacement
      measurements effectively and robustly for the H-type sensor and the technique is
      applicable for practical geo-engineering applications. 

PMID- 24858959
TI  - Detection of Schistosoma mansoni infection by TaqMan(r) Real-Time PCR in a
      hamster model.
AB  - An experimental study in hamsters was performed to evaluate the capability for
      detecting Schistosoma mansoni DNA in serum and fecal samples during the pre and
      post-egg-laying periods of infection using TaqMan(r) Real-Time PCR system (qPCR),
      was compared with the circumoval precipitin test (COPT) and the Kato-Katz
      technique, especially among individuals with low parasitic burden. Twenty-four
      hamsters were infected with cercariae. Three hamsters were sacrificed per week
      under anesthesia, from 7 days post infection (DPI) up to 56 DPI. A serum sample
      and a pool of feces were collected from each hamster. The presence of S. mansoni
      eggs in fecal samples was evaluated by Kato-Katz method and in the hamsters gutby
      histopathology. Detection of S. mansoni DNA was performed using qPCR and S.
      mansoni antibody using COPT. The first detection of eggs in feces by Kato-Katz
      method and S. mansoni DNA in feces by qPCR occurred 49 DPI. Nevertheless, S.
      mansoni DNA was detected in serum samples from 14 up to 56 DPI. COPT was positive
      at 35 DPI. The results not only confirm the reliability of S. mansoni DNA
      detection by qPCR, but also demonstrate that serum is a trustworthy source of DNA
      in the pre patent infection period.

PMID- 24858961
TI  - A new method for ultrasound detection of interfacial position in gas-liquid two
      phase flow.
AB  - Ultrasonic measurement techniques for velocity estimation are currently widely
      used in fluid flow studies and applications. An accurate determination of
      interfacial position in gas-liquid two-phase flows is still an open problem. The
      quality of this information directly reflects on the accuracy of void fraction
      measurement, and it provides a means of discriminating velocity information of
      both phases. The algorithm known as Velocity Matched Spectrum (VM Spectrum) is a
      velocity estimator that stands out from other methods by returning a spectrum of
      velocities for each interrogated volume sample. Interface detection of free
      rising bubbles in quiescent liquid presents some difficulties for interface
      detection due to abrupt changes in interface inclination. In this work a method
      based on velocity spectrum curve shape is used to generate a spatial-temporal
      mapping, which, after spatial filtering, yields an accurate contour of the air
      water interface. It is shown that the proposed technique yields a RMS error
      between 1.71 and 3.39 and a probability of detection failure and false detection
      between 0.89% and 11.9% in determining the spatial-temporal gas-liquid interface
      position in the flow of free rising bubbles in stagnant liquid. This result is
      valid for both free path and with transducer emitting through a metallic plate or
      a Plexiglas pipe. 

PMID- 24858962
TI  - Point-of-care diagnostic tools to detect circulating microRNAS as biomarkers of
      disease.
AB  - MicroRNAs or miRNAs are a form of small non-coding RNAs (ncRNAs) of 19-22
      nucleotides in length in their mature form. miRNAs are transcribed in the nucleus
      of all cells from large precursors, many of which have several kilobases in
      length. Originally identified as intracellular modulators of protein synthesis
      via posttranscriptional gene silencing, more recently it has been found that
      miRNAs can travel in extracellular human fluids inside specialized vesicles known
      as exosomes. We will be referring to this miRNAs as circulating microRNAs. More
      interestingly, the miRNA content inside exosomes changes during pathological
      events. In the present review we analyze the literature about circulating miRNAs
      and their possible use as biomarkers. Furthermore, we explore their future in
      point-of-care (POC) diagnostics and provide an example of a portable POC
      apparatus useful in the detection of circulating miRNAs. 

PMID- 24858963
TI  - Tolerance of, and metabolic effects of, preoperative oral carbohydrate
      administration in children - a preliminary report.
AB  - BACKGROUND: The need for long preoperative fasting has been questioned. Recent
      data shows that intake of an oral carbohydrate-containing clear fluid prior to
      anaesthesia is safe and may have a positive impact on recovery and metabolic
      status and could improve glucose tolerance. Such solutions are routinely used in
      adults but not children. The aim of this study was to evaluate the safety,
      tolerance and influence of oral carbohydrate on selected metabolic parameters in
      children. METHODS: With ethics committee approval and parental informed consent,
      20 children, aged 4-17 years, ASA status I or II, scheduled for abdominal or
      thoracic surgery were randomised either to Group 1 - receiving a 12.6%
      carbohydrate-containing drink (10 mL kg(-1) the evening before surgery and two
      hours before anaesthesia), or the control Group 2 - fasting. Serum glucose and
      insulin concentration were measured four times: before and after anaesthesia, in
      the evening after surgery, and the following morning. IGF-1 concentration was
      measured once, before surgery. Insulin resistance was assessed by the HOMA-IR
      equation. RESULTS: Oral carbohydrate solution was well tolerated and no adverse
      events were noted. Glucose concentrations were within the normal range in both
      groups. Insulin concentration did not show significant differences between
      groups, however before surgery it tended to be lower in Group 1. Insulin
      resistance after surgery was significantly higher in Group 2 (2.0 vs. 0.62, P =
      0.03), also the increase in insulin resistance after operation was significant
      only in the control group (P = 0.03). CONCLUSION: Oral carbohydrates are safe,
      well tolerated and do not cause any perioperative adverse events. They seem to
      improve postoperative metabolism by decreasing insulin resistance.

PMID- 24858964
TI  - Anaesthesia of conjoined twins - case series.
AB  - As any complex surgical procedure, separation of conjoined twins requires complex
      anaesthesia management that is a prerequisite of performing the operation, while
      complex postoperative care is a decisive factor in the survival of the patients.
      The paper describes the anaesthetic management for surgical operations in ten
      sets of conjoined twins in the Children's Hospital of Cracow during 1977-2005.
      The anaesthetic technique and associated problems are summarized.

PMID- 24858965
TI  - Changes of procalcitonin level in multiple trauma patients.
AB  - BACKGROUND: Some aspects of the pathophysiology of complications in multiple
      trauma patients still remain unclear. Mediators of inflammation have been
      postulated as playing a key role in being responsible for life threatening
      complications of multiple trauma patients. The objective of this study was to
      evaluate the prognostic value of procalcitonin (PCT) level in multiple trauma
      patients. METHODS: A prospective study took place including patients with
      multiple trauma hospitalised in several hospital units. PCT level was measured in
      blood from 45 patients, aged 18-70 years using enzyme-linked immunoassay. The
      patients were divided into three groups: group I - individuals with multiple
      trauma with central nervous system injury; group II - those with multiple trauma
      without CNS injury; and group III - patients with isolated central nervous system
      injury. RESULTS: Initial PCT levels were below 0.5 ng mL(-1) regardless of the
      cause of trauma. In the 24th hour of observation, a statistically significant
      increase of PCT concentration vs. initial levels was recorded in all groups of
      patients. Then PCT levels decreased significantly at the 3rd measurement point in
      all groups, and they remained unchanged until the last measurement. The highest
      levels of PCT were observed in multiple trauma patients without CNS injury (group
      II). In this group of patients, a significantly longer duration of surgery in the
      post-trauma period affected PCT levels. PCT concentrations in patients who died
      were significantly greater than in survivors. CONCLUSIONS: A long lasting
      elevated concentration of procalcitonin in the post-traumatic period, or its
      repeated increase, is a good marker of developing complications observed earlier
      than clinical manifestations.

PMID- 24858966
TI  - Incidence, characteristics and management of pain in one operational area of
      medical emergency teams.
AB  - BACKGROUND: Experience of pain associated with both chronic as well as acute
      medical conditions is a main cause for call for ambulance. The aim of this study
      was to establish both frequency and characteristics of pain reported by patients
      treated in pre-hospital environment in a single operational area. The
      supplementary goal was an analysis of methods of pain alleviation applied by
      medical personnel in the above described scenario. METHODS: The written
      documentation of 6 months of year 2009 provided by doctor-manned as well as
      paramedic-only ambulances operating in Tatra county, Malopolska, Poland was
      analyzed. RESULTS: Medical personnel inquired about pain experienced in 57.4% of
      cases, 10-point numerical rating scale was used in 22.3% of patients. Pain was
      reported by 43.8% of patients, the most frequent reasons of experienced pain were
      trauma and cardiovascular diseases. In almost half of the cases pain was referred
      to the areas of chest and abdomen. Non-traumatic pain was reported by 47.7% of
      patients, post-traumatic in 41.3% of cases, 11% of subjects reported ischemic
      chest pain. 42.3% of pain-reporting patients received some form of analgesia, yet
      only 3% of subjects in this group received opiates. Personnel of paramedic-only
      ambulances tended to use pain intensity scale more often (P < 0.01), yet
      administered pain alleviating drugs noticeably less often than the doctor-manned
      teams (P < 0.01). CONCLUSION: The use of pain alleviating drugs, opiates
      especially, was inadequate in proportion to frequency and intensity of pain
      reported by patients. General, nation-wide standards of pain measurement and
      treatment in pre-hospital rescue are suggested as a means to improve the efficacy
      of pain reduction treatment.

PMID- 24858967
TI  - Two cases of the "cannot ventilate, cannot intubate" scenario in children in view
      of recent recommendations.
AB  - We present two cases of a "cannot ventilate, cannot intubate" scenario in
      children in view of the latest guidelines for the management of unexpectedly
      difficult paediatric airways. Case 1 was a 5-year-old boy with Treacher-Collins
      syndrome who suffered gastric rupture due to gastric distension with oxygen
      during attempts to maintain oxygenation at the induction of anaesthesia.
      Difficulties in maintaining this patient's airways should be attributed to
      functional rather than anatomical obstruction, because no such problem occurred
      during subsequent anaesthetic inductions; therefore muscle relaxation would be
      helpful in this situation. In case 2, vecuronium was used in a 10-month-old
      infant scheduled for elective laryngoscopy because of stride due to vocal cord
      paralysis. Because of congenital maxillo-facial malformation, the infant could
      not be intubated, and ventilation via a face mask became difficult. Facing rapid
      deterioration of oxygenation, neuromuscular block was reversed with the use of
      sugammadex. The recovery of spontaneous respiration was almost immediate, and
      normal motor function returned within 90 s. Functional airway obstruction due to
      laryngospasm, insufficient depth of anaesthesia, or opioid-induced muscle
      rigidity with glottic closure can occur in a healthy child, as well as in a child
      with difficult airways, and requires clear concepts and therapeutic algorithms.
      Recent paediatric guidelines for the management of unexpectedly difficult airways
      stress the role of muscle relaxants in overcoming functional airway obstruction.
      The possibility of reversing neuromuscular block produced by rocuronium or
      vecuronium with sugammadex to awaken the patient adds to the safety of this
      algorithm.

PMID- 24858968
TI  - Efficacy of plasma exchange in septic shock: a case report.
AB  - The mortality rate for severe sepsis and septic shock remains high. Additionally,
      this life-threatening state poses serious difficulties for the treatment of
      patients. Unfortunately, the mechanism of sepsis is complex and not well
      understood. In this paper, we present the case of a 2.5-year-old female with
      septic shock treated with plasma exchange (PE) as a nonstandard therapy. We
      analysed the medical history of disease, including patient data, physical
      examination, laboratory tests and treatment. Unexpectedly, we achieved clinical
      improvement after the first PE. During PE, the dose of catecholamine was reduced.
      In addition, the level of C-reactive protein seemed to be a better predictor of
      the efficacy of PE in septic shock compared to procalcitonin. We conclude that PE
      may improve the survival rate for patients with septic shock. These data could be
      useful in the search and introduction of new or alternative methods of treatment
      for critically ill children.

PMID- 24858969
TI  - Methods to prevent intraoperative hypothermia.
AB  - Inadvertent intraoperative hypothermia is by far the most commonly occurring
      anaesthesia-related complication. It can increase the risk of unfavourable events
      perioperatively. Higher rates of surgical site infections and blood transfusions,
      coagulation and drug metabolism disturbances are said to be the most relevant
      issues linked to this phenomenon. Although they have been available for several
      years now, dedicated systems designed to prevent it are still not part of routine
      anaesthesia conducted in Poland. This review aims to discuss the factors which
      may potentially increase the risk of hypothermia, and to present tools that are
      readily available and effective in perioperative temperature management.

PMID- 24858970
TI  - Do we really know the pharmacodynamics of anaesthetics used in newborns, infants
      and children? A review of the experimental and clinical data on
      neurodegeneration.
AB  - The practices of anaesthesiology and intensive therapy are difficult to imagine
      without sedation or general anaesthesia, regardless of whether the patient is a
      newborn, baby, child or adult. The relevant concerns for children are distinct
      from those for adults, primarily due to the effects of anatomical, physiological
      and pharmacokinetic-pharmacodynamic (PK/PD) differences, which become
      increasingly important in the brains of children as they develop. The process of
      central nervous system maturation in humans lasts for years, but its greatest
      activity (myelination and synaptogenesis) occurs during the fetal period and the
      first two years of life. Many experimental studies have demonstrated that
      exposure to anaesthetic drugs during this period can induce neurodegenerative
      changes in the central nervous systems of animals. The extrapolation of these
      results directly to humans must be performed with great caution, but
      anaesthesiologists around the world must begin to debate the safety of general
      anaesthesia in humans. Prospective trials should continue being carried out, and
      anaesthesia and surgery, delayed if possible among the smallest patients. The
      simultaneous use of different anaesthetics with the same potential
      neurotoxicities should also be avoided, potentially in favour of regional
      anaesthesia techniques, in this group of patients.

PMID- 24858972
TI  - History of treatment of conjoined twins.
AB  - This paper presents a history of the treatment of conjoined twins. The first
      mention of this malformation comes from the Neolithic period. Conjoined twins
      were depicted in mythologies of ancient peoples. The present paper focuses on the
      theories of formation of Siamese twins and attempts at their separation.
      Moreover, the history of treatment of conjoined twins in Poland is described.

PMID- 24858971
TI  - Procedural sedation and analgesia for gastrointestinal endoscopy in infants and
      children: how, with what, and by whom?
AB  - Endoscopic procedures involving the gastrointestinal tract have been successfully
      developed in paediatric practice over the last two decades, improving both
      diagnosis and treatment in many children's gastrointestinal diseases. In this
      group of patients, experience and co-operation between
      paediatricians/endoscopists and paediatric anaesthesiologists should help to
      guarantee the quality and safety of a procedure and should additionally help to
      minimise the risk of adverse events which are greater the smaller the child is.
      This principle is more and more important especially since the announcement of
      the Helsinki Declaration on Patient Safety in Anaesthesiology in 2010,
      emphasising the role of anaesthesiology in promoting safe perioperative care. The
      Helsinki Declaration has been endorsed by all European anaesthesiology
      institutions as well as the World Health Organisation's 'Safe Surgery Saves
      Lives' initiative including the 'Surgical Safety Checklist'. Although most of
      these procedures could be performed by paediatricians under procedural sedation
      and analgesia, children with congenital defects and serious coexisting diseases
      (ASA >= III) as well as the usage of anaesthetics (e.g. propofol) must be managed
      by paediatric anaesthesiologists. We have reviewed the specific principles
      employed during qualification and performance of procedural sedation and
      analgesia for gastrointestinal endoscopy in paediatrics. We have also tried to
      answer the questions as to how, with what, and by whom, procedural sedation for
      gastrointestinal endoscopy in children should be performed.

PMID- 24858973
TI  - Anaesthesia of conjoined twins.
AB  - Conjoined twins have been a source of fascination to the public and the medical
      profession for centuries. Their birth was initially viewed as an ominous sign of
      impending disaster. Since Middle Ages into the 19th century they were regarded as
      monstrosities and were exhibited at circuses and sideshows. The frequency of
      conjoined twins is approximately 1 in 50,000 gestation, but many of them die in
      utero, are terminated or stillborn. The true incidence is estimated to be 1 in
      200,000 live births. This article gives an overview of Siamese twins and of the
      prenatal diagnosis in assessing the prognosis, anaesthetic and post-natal
      surgical management and outcome. Anaesthesia for conjoined twins surgery, whether
      prior to or for separation, is an enormous challenge to the anaesthesiologist.
      The site and complexity of the conjunction affect management of the airway, an
      intravenous access, the extent of blood and number of surgical specialties
      involved. Preoperative assessment and planning with interdisciplinary
      communication and cooperation is vital to the success of the operations.
      Meticulous attention to detail, monitoring and vigilance are mandatory.

PMID- 24858974
TI  - Intensive care of conjoined twins.
AB  - Conjoined twinning is one of the most uncommon congenital anomalies. Maintenance
      in an intensive care setting during this time allows for close monitoring,
      stabilisation, and nutritional supplementation of the infants as necessary to
      optimise preoperative growth and development. The birth of conjoined twins is a
      very difficult and dramatic moment for parents. It is also a very difficult
      situation for the team of physicians, nurses and other required hospital staff to
      carry out treatment and care of these specific developmental anomalies. The
      diagnostics and treatment in this extraordinary situation requires close
      cooperation of the multidisciplinary medical team, which includes their personal
      experience and medical knowledge, with a team of intensive care unit nurses. This
      report presents the rules in cease of conjoined twins during their intensive care
      unit stay with special reference to the proceedings before and after complete
      separation.

PMID- 24858977
TI  - Isolated metastasis of uterine leiomyosarcoma to the pancreas: Report of a case
      and review of the literature.
AB  - INTRODUCTION: Metastatic tumors of the pancreas are uncommon and rarely
      detectable clinically. Metastases to the pancreas are rare. We present a patient
      with pancreatic metastases from a leiomyosarcoma of the uterus and review the
      literature about the clinical features of pancreatic metastasis and its surgical
      management. PRESENTATION OF CASE: A 40-year-old woman, who underwent
      hysterectomy, left oophorectomy, omentectomy and lymp node dissection for
      leiomyosarcoma of the uterus. At the follow up, the patient complained of non
      specific abdominal discomfort. Preoperative diagnosis were pancreatic pseudocyst,
      cystadenoma or cystadenocarcinoma. At laparotomy, a cystic mass was found in the
      tail of the pancreas which was invased to the transverse colon mesenterium and
      the spleen. Distal pancreatectomy with splenectomy and transverse colon resection
      was performed. Histologically, the tumor was evaluated as poorly differentiated
      leiomyosarcoma. DISCUSSION: Metastatic lesions of the pancreas are uncommon and
      less than 2% of all pancreatic malignancies. However a few cases of
      leiomyosarcoma with metastases to the pancreas have been reported in the
      literature. Before deciding that the lesion in the pancreas was metastasis,
      primary leiomyosarcoma of the pancreas had to be ruled out. Histologically,
      leiomyosarcoma of the pancreas contains interlacing spindle cells with varying
      degrees of atypia and pleomorphism. The surgical approach to the pancreatic
      metastases must be aimed complete excision of the tumor with a wide negative
      margin of clear tissue and maximum preservation of pancreatic remnant if
      possible. CONCLUSION: In the absence of widespread metastatic disease, aggressive
      surgical approach with negative margins must be aimed.

PMID- 24858975
TI  - 25-Hydroxyvitamin D level does not reflect intestinal calcium absorption: an
      assay using strontium as a surrogate marker.
AB  - There is conflicting evidence as to the optimal serum 25-hydroxyvitamin D
      [25(OH)D] concentration for intestinal calcium absorption (Abs-Ca). Our purpose
      was to assess the relationship between vitamin D status and Abs-Ca in
      postmenopausal women. Fifty volunteers with low bone mass were grouped according
      to their serum 25(OH)D concentration as follows: mild deficient, <50 nmol/L (DEF)
      and sufficient, >=75 nmol/L (SUF). The subjects were submitted to an oral
      strontium overload test to assess their Abs-Ca. Fasting blood samples were
      obtained to perform the relevant hormonal and biochemical tests. After the
      subjects received the test solution, blood samples were drawn at 30, 60, 120, and
      240 min to determine the strontium concentrations. Abs-Ca was indirectly
      expressed as the area under the serum strontium concentration curve (AUC). A
      repeated measures ANOVA was performed to determine the differences among the
      groups. Pearson's correlation and multiple linear regression analysis were used
      to study the associations between the variables. The mean 25(OH)D and 1,25
      dihydroxyvitamin D [1,25(OH)2D] concentrations differed between the groups (SUF
      vs. DEF) as follows: 98.7 +/- 18.2 vs. 38.4 +/- 8.5 nmol/L (p < 0.001) and 36.2
      +/- 10.2 vs. 24.9 +/- 4.6 pg/mL (p < 0.001), respectively. There was no
      statistically significant difference between the groups for parathyroid hormone
      and AUC. Only 1,25(OH)2D influenced the strontium absorption in the last 2 h of
      the test. In the studied population, no correlation between levels of 25(OH)D and
      Abs-Ca was found. Only 1,25(OH)2D influenced Abs-Ca as measured by a strontium
      absorption test.

PMID- 24858978
TI  - Preoperative diagnosis of an asymptomatic cancer restricted to the cystic duct.
AB  - INTRODUCTION: Even now, cystic duct cancer (CDC) as defined by Farrar is rare and
      has a better prognosis than gallbladder cancer, although CDC as defined by Ozden
      et al., the definition of which could apply to early and advanced cases of CDC,
      is not rare and has a poorer prognosis than the CDC defined by Farrar.
      PRESENTATION OF CASE: A 78-year-old woman with no complaints was found to have a
      tumor restricted to the cystic duct. Three cytology examinations of the patient's
      bile could not establish that the tumor was an adenocarcinoma. However,
      adenocarcinoma was suspected due to the hypervascularity shown on contrast
      enhanced computed tomography. Cholecystectomy and extrahepatic bile duct
      resection with D2 lymph node dissection was performed. The pathological study
      revealed it to be CDC. Her postoperative course has been uneventful and without
      recurrence for 21 months. DISCUSSION: At their first medical examination, many
      CDC patients are found to have such advanced spread of the cancer to adjacent
      organs that an extended operation might be necessary. As in our case, better
      patient outcome results when no lymph node or remote metastasis is present.
      CONCLUSION: Diagnosing CDC as early as possible contributes to curative
      resections and favorable patient outcomes and also allows surgeons to recommend a
      mini-invasive procedure to their patients rather than extended resection
      including that of adjacent organs.

PMID- 24858976
TI  - Osteocalcin, but not deoxypyridinoline, increases in response to isoflurane
      induced anaesthesia in young female guinea pigs.
AB  - The effect of the inhaled anaesthetic isoflurane was investigated on bone
      biomarkers, both during maturation and on minerals and glucose postpartum. Female
      guinea pigs (n = 10) were anaesthetized during maturation (5 and 9 weeks) and
      postpartum (26 weeks of age) with isoflurane during dual-energy X-ray
      absorptiometry scanning. Blood collection was performed at all ages before and
      after anaesthesia for measurement of plasma osteocalcin (OC), total
      deoxypyridinoline (tDPD), and cortisol. Postpartum measurements also included:
      blood ions, acid-base parameters and glucose, plasma minerals, total alkaline
      phosphatase (tALP), and albumin. Plasma OC concentration almost doubled after
      exposure to isoflurane at 5 weeks (30.1 +/- 5.0-57.9 +/- 11.2 nmol/L, p < 0.001)
      and at 9 weeks (29.1 +/- 7.5-62.9 +/- 15.9 nmol/L, p < 0.001), but did not change
      postpartum (3.7 +/- 3.3-4.3 +/- 3.9 nmol/L, p = 0.88). There was no effect of
      isoflurane exposure on plasma tDPD at any age. Plasma cortisol increased after
      exposure to isoflurane at 9 weeks (1859.6 +/- 383.2-2748.0 +/- 235.3 nmol/L, p <
      0.01) and postpartum (3376.7 +/- 322.2-4091.6 +/- 195.6 nmol/L, p < 0.001) but
      not at 5 weeks (2088.3 +/- 326.4-2464.1 +/- 538.0 nmol/L, p > 0.05). Blood
      ionized Ca(2+), Na(+) and plasma total Ca did not change, whereas plasma albumin
      decreased, and inorganic phosphate (PO4) and Cl(-) increased upon exposure to
      isoflurane. Isoflurane decreased tALP (43.2 +/- 6.6-40.2 +/- 5.9 IU/L, p = 0.01)
      and increased glucose (7.5 +/- 0.6-10.9 +/- 1.7 mmol/L, p < 0.0001) postpartum.
      Isoflurane inflates the assessment of a bone-derived biomarker, OC, during rapid
      growth, but not following pregnancy when formation is very low. Measurements
      prior to anaesthesia are recommended to reflect normal metabolism. 

PMID- 24858979
TI  - An unusual cause of small bowel obstruction caused by a Richter's-type hernia
      into the urinary bladder.
AB  - INTRODUCTION: The authors present an unusual case of small bowel obstruction in a
      62-year-old man. PRESENTATION OF CASE: A 62-year-old man with a background of
      transitional cell carcinoma (TCC) of the bladder presented to the emergency
      department with abdominal pain, distension, vomiting and had not opened his
      bowels for three days. 3 weeks previously he had a repeat Transurtheral resection
      of bladder tumour (TURBT), during which there was an iatrogenic perforation of
      the bladder. A CT scan of the abdomen and pelvis revealed small bowel obstruction
      but did not identify a cause. At laparotomy the cause of the obstruction was
      identified as a section of the small bowel that had partially herniated into the
      bladder, via the perforation. The defect was repaired and the patient made an
      uneventful recovery. DISCUSSION: Herniation of the bowel into a defect in the
      bladder wall is a rare event with only 6 previous cases reported in the
      literature. It can cause signs and symptoms of bowel obstruction. CONCLUSION: In
      patients with known bladder perforations who present with symptoms and signs of
      bowel obstruction, bowel herniation into the bladder should be considered. Early
      surgical intervention may be necessary if the patient is clinically unwell with
      appropriate symptoms and signs and imaging does not provide conclusive answer.

PMID- 24858980
TI  - A modified technique to extract fractured femoral stem in revision total hip
      arthroplasty: A report of two cases.
AB  - INTRODUCTION: The removal of well-fixed broken femoral component and cement
      mantle can be extremely demanding, time consuming and potentially damaging to the
      host bone. Different methods have been described to extract broken femoral stem
      yet this remains one of the most challenging prospect to the revision hip
      surgeon. PRESENTATION OF CASE: The authors present two cases underwent a modified
      sliding cortical window technique utilising a tungsten carbide drill, Charnley
      pin retractor and an orthopaedic mallet to aid extraction of a fractured cemented
      femoral stem in revision total hip arthroplasty. DISCUSSION: The modified
      technique offers a simple and controlled method in extracting a well fixed
      fractured cemented femoral stem. It has the advantage of retaining the cement
      mantle with subsequent good seal of the femoral cortical window secured with
      cable ready system. Furthermore, tungsten carbide drill bit and Charnley pin
      retractor are relatively readily available to aid the extraction of the broken
      stem. Finally, it yields the option of implanting a standard femoral stem and
      obviates the need for bypassing the cortical window with long revision femoral
      component. CONCLUSION: Fractured femoral stem is a rare yet a complex and very
      demanding prospect to both patients and hip surgeons. The sliding cortical window
      technique utilising tungsten carbide drill and Charnley pin retractor is
      technically easy and most importantly; preserves host bone stock with cement-in
      cement revision hip arthroplasty. We believe this technique can be added to the
      armamentarium of revision hip surgeon when faced with the challenge of extracting
      a fractured cemented femoral stem.

PMID- 24858981
TI  - Single-incision laparoscopic surgery for gallstone ileus: An alternative surgical
      procedure.
AB  - INTRODUCTION: Gallstone ileus (GI) results from the passage of a stone through a
      cholecystoenteric fistula, subsequently causing a bowel obstruction. The ideal
      treatment procedure for GI remains controversial. PRESENTATION OF CASE: A 63-year
      old female was admitted to our hospital following persistent nausea and vomiting
      for 7 days. Computed tomography revealed a partially calcified 4-cm circular
      object in the jejunum, and the proximal intestine was dilated, with concomitant
      pneumobilia. Based on the preoperative diagnosis of GI, enterotomy with stone
      extraction by single-incision laparoscopic surgery (SILS) was performed. The
      patient's postoperative course was uneventful, and the cholecystoduodenal fistula
      closed spontaneously 4 months after the surgery. DISCUSSION: Recent studies have
      reported that enterotomy with stone extraction alone is associated with better
      outcomes than with more invasive techniques. This case also suggests that
      enterotomy with stone extraction alone and careful postoperative follow-up is
      feasible for the management of GI. Although the use of laparoscopy in the
      management of GI has been described previously, laparoscopic surgery has not been
      widely performed, and SILS is not generally performed. When only this less
      demanding procedure is required, laparoscopic surgery, including SILS, can be a
      viable option. CONCLUSION: SILS can be an alternative surgical procedure for the
      management of GI.

PMID- 24858982
TI  - Multiple desmoid tumors in a patient with Gardner's syndrome - Report of a case.
AB  - INTRODUCTION: Desmoid tumor (DT) is a common manifestation of Gardner's Syndrome
      (GS), although it is a rare condition in the general population. DT in patients
      with GS is usually located in the abdominal wall and/or intra-abdominal cavity.
      PRESENTATION OF CASE: We report a case of a 32 years-old female patient with
      familial adenomatous polyposis (FAP), who was already submitted to total
      colectomy and developed multiple DT, located in the abdominal wall and in the
      left breast. The patient underwent several surgical procedures, with a
      multidisciplinary team of surgeons. Wide surgical resections of the left breast
      and the abdominal wall tumors were performed in separate steps. Polypropylene
      mesh reconstruction and muscle flaps were needed to cover the defects of the
      thoracic and abdominal walls. After partial necrosis of the adipose-cutaneous
      flap in the abdomen that required a new skin graft, she had a satisfactory
      outcome with complete healing of the surgical incisions. DISCUSSION: DT is
      frequent in GS, however, breast localization is very rare, with few cases
      reported in the literature. Recurrence of DT is not negligible, even after a wide
      surgical resection. GS patients must be followed up closely, and clinical
      examination, associated with imaging studies, should be performed to detect any
      signs of tumor. CONCLUSION: DT represents one of the most significant causes of
      the morbidity and mortality that affects FAP patients following colectomy. In
      general, the surgical procedures to excise DT are highly complex, requiring a
      multidisciplinary team.

PMID- 24858983
TI  - The first use of Resonance((r)) metallic ureteric stent in a case of obstructed
      transplant kidney.
AB  - INTRODUCTION: To date, double JJ stent is the mainstay ureteric stent used in a
      transplant kidney. We herein report the first use of Resonance((r)) metallic
      ureteric stent to manage ureteric obstruction in a transplant kidney.
      PRESENTATION OF CASE: A 45-year-old lady underwent an uneventful living related
      donor renal transplantation. Due to post-operative pelvi-ureteric obstruction and
      recurrent obstruction following multiple distal stent migration and expulsion
      necessitated frequent nephrostomy insertion and antegrade stenting, she underwent
      challenging but successful retrograde insertion of a 12 centimetres long and size
      6.0 French Cook Resonance((r)) metallic ureteric stent which was performed under
      general anaesthesia. DISCUSSION: Metallic ureteric stents are a fairly recent
      introduction to modern urology and they have been successfully used in the
      management of benign and malignant obstruction of ureter. CONCLUSION: This is the
      first case of therapeutic metallic ureteric stent insertion in a transplant
      kidney.

PMID- 24858984
TI  - Management of fistula of ileal conduit in open abdomen by intra-condoit negative
      pressure system.
AB  - INTRODUCTION: We aimed to present the management of a patient with fistula of
      ileal conduit in open abdomen by intra-condoid negative pressure in conjunction
      with VAC Therapy and dynamic wound closure system (ABRA). PRESENTATION OF CASE:
      65-Year old man with bladder cancer underwent radical cystectomy and ileal
      conduit operation. Fistula from uretero-ileostomy anastomosis and ileus occurred.
      The APACHE II score was 23, Mannheim peritoneal index score was 38 and Bjorck
      score was 3. The patient was referred to our clinic with ileus, open abdomen and
      fistula of ileal conduit. Patient was treated with intra-conduid negative
      pressure, abdominal VAC therapy and ABRA. DISCUSSION: Management of urine fistula
      like EAF in the OA may be extremely challenging. Especially three different
      treatment modalities of EAF are established in recent literature. They are
      isolation of the enteric effluent from OA, sealing of EAF with fibrin glue or
      skin flep and resection of intestine including EAF and re-anastomosis. None of
      these systems were convenient to our case, since urinary fistula was deeply
      situated in this patient with generalized peritonitis and ileus. CONCLUSION:
      Application of intra-conduid negative pressure in conjunction with VAC therapy
      and ABRA is life saving strategies to manage open abdomen with fistula of ileal
      conduit.

PMID- 24858985
TI  - Totally laparoscopic intracorporeal anastomosis with natural orifice specimen
      extraction (NOSE) techniques, particularly suitable for bowel endometriosis.
AB  - The objective of this retrospective study was to evaluate the feasibility of
      natural orifice specimen extraction (NOSE) techniques in 41 patients undergoing
      bowel resection for treatment of deep infiltrating endometriosis. In all patients
      laparoscopic treatment of rectovaginal endometriosis with bowel resection had
      been performed. In 32 patients the classic approach was adopted (group 1), and in
      9 a NOSE technique was performed (group 2). Demographic, operative, and
      postoperative data were compared. Statistical analyses were performed using SPSS
      software, version 16.0. When needed, qualitative variables were compared using
      the chi(2) test or the Fisher exact test. Quantitative variables using the t-test
      were used. The threshold of statistical significance was set at p = .05. No
      statistically significant difference was observed between the 2 groups. Eight
      complications (19.5%) were observed, 2 minor (4.8%) and 6 major (14.6%). Of major
      complications, 2 were observed in the NOSE group (n = 2; 22.2%). It was concluded
      that the NOSE technique is a feasible approach in patients undergoing bowel
      resection for treatment of deep infiltrating endometriosis.

PMID- 24858986
TI  - Hemivaginal septum resection in a patient with a rare variant of Herlyn-Werner
      Wunderlich syndrome.
AB  - Herlyn-Werner-Wunderlich syndrome is characterized by a triad of uterine
      didelphys, obstructed hemivagina, and ipsilateral renal agenesis. The syndrome
      should be suspected in any young woman with abdominal pain or cyclic
      dysmenorrhea, and radiologic evidence of mullerian duct and renal anomalies.
      Herein is presented the case of a 25-year-old woman with a rare variant of Herlyn
      Werner-Wunderlich syndrome, characterized by an anomalous connection between the
      2 endocervical canals, who underwent hemivaginal septum resection to relieve
      progressively worsening dysmenorrhea. The right hemivaginal septum was resected
      medially from the left cervix and laterally off the right vaginal wall.
      Hydrodissection between the hemivaginal septum and right cervix facilitated
      surgical resection. After resection of the hemivaginal septum there was complete
      resolution of dysmenorrhea and no recurrence of hematometra or hematocolpos. 

PMID- 24858987
TI  - Long-term fertility after laparoscopy for endometriosis-associated pelvic pain in
      young adult women.
AB  - STUDY OBJECTIVE: To describe the long-term fertility outcomes in young patients
      with endometriosis-associated pelvic pain treated with laparoscopic surgery.
      DESIGN: Retrospective case series (Canadian Task Force classification II-2).
      SETTING: Tertiary care hospital. PATIENTS: Women aged 18 to 25 years who
      underwent laparoscopic surgery between 2000 and 2005 at the Cleveland Clinic
      Foundation solely to treat endometriosis-associated pelvic pain. INTERVENTIONS:
      Patients answered a telephone or mail survey questionnaire assessing fertility
      outcome after surgery. MEASUREMENTS AND MAIN RESULTS: Twenty-eight of 74 eligible
      patients (37.8%) were enrolled in the study. With a median (interquartile range)
      age of 23.5 (1.5) years at follow-up, these patients completed the telephone or
      postal questionnaire to assess fertility outcomes at follow-up of 102.5 (16.6)
      months. In most participants the diagnosis was less advanced endometriosis (stage
      I, 60.7%; stage II, 28.6%). Twenty women (71.4%) had at least 1 pregnancy during
      follow-up that resulted in a live birth, of which >80% were spontaneous without
      the use of assisted reproductive technologies. CONCLUSION: Long-term pregnancy
      rates are excellent in young women undergoing laparoscopic surgery to treat
      pelvic pain. However, a future prospective study is needed to determine whether
      laparoscopy has any hindrance on future fertility.

PMID- 24858988
TI  - Greater surgical precision of a flexible carbon dioxide laser fiber compared to
      monopolar electrosurgery in porcine myometrium.
AB  - The objective of this experimental animal study was to compare the surgical
      precision of a flexible CO2 laser fiber with that of monopolar electrosurgery in
      porcine myometrium. The subjects were 6 live adult non-pregnant female pigs.
      Linear injury to the uterine horns was created using a flexible CO2 laser fiber
      at 5W, 10W, and 15W and with monopolar electrosurgery at 10W, 20W, 30W, and 40W
      in both cut and coagulation modes. Hysterectomy was then performed in the live
      animals. Cross-sections of the tissue were processed and stained using Masson
      trichrome to differentiate damaged from undamaged myometrium. Measurement means
      were compared using analysis of variance with Tukey honest significant difference
      correction; p <.05 indicated significance. Incision width of the laser at 5W and
      10W was significantly less than both monopolar coagulation at all power settings
      and monopolar cut at 30W and 40W (all p <.01), at 5W was also significantly less
      than monopolar cut at 10W (p = .03), and at 15W was significantly less than
      monopolar coagulation at 40W (p = .001). Incision depth of the laser at 5W was
      significantly less than monopolar coagulation at 40W and laser at 15W (both p =
      .01), at 15W was significantly greater than monopolar coagulation at 10W and
      monopolar cut at 10, 20, and 30W (p <=.01), and increased proportional to power
      for all 3 energy types. Collateral thermal damage width at all laser power
      settings was significantly less than at all monopolar coagulation power settings
      (p <=.04) with the exception of the laser at 15W compared with monopolar
      coagulation at 10W (p = .30), and at all laser power settings was significantly
      less than at all monopolar coagulation power settings (p <.001). Collateral
      thermal damage depth of the laser at 5W and 10W was significantly less than
      monopolar cut at 30W (p <=.002) and increased proportional to power in monopolar
      coagulation mode but remained constant with the laser. Incising efficiency of the
      laser at 5W was significantly greater than monopolar coagulation at 10W (p =
      .04), at 10W was significantly greater than at all monopolar power settings (p
      <=.007) except cut at 40W (p = .29), and at 15W was significantly greater than
      that of every other energy type and power setting tested (p <=.04). These
      findings support the hypothesis that CO2 laser energy delivered via a flexible
      fiber system would exhibit greater surgical precision than monopolar
      electrosurgery, in both cut and coagulation modes, as defined by 3 parameters:
      incising efficiency, changes in incision depth compared with width as power
      increases, and variability in the resulting incision measurements. Because
      increased thermal damage has been associated with delayed tissue necrosis and
      adhesion formation, these findings prompt the design of a comparative survival
      animal study to assess additional clinically relevant parameters.

PMID- 24858989
TI  - Functional significance of microsatellite markers.
AB  - The review summarizes literature data on the positive results of association
      studies between the length of microsatellite repeats and predisposition to
      pathologies. Actually, the data can be classified according to the localization
      of the microsatellite: in the gene promoter, in the part of exon 1 coding the
      signal sequence, in gene introns, in the coding areas of genes, and in 3'
      untranslated regions. The functional significance of microsatellite length
      changes can be evaluated in many cases. The authors came up to the conclusion
      that further studies on microsatellite associations with diseases remain
      prospective as they reflect changes in the gene functional activity. 

PMID- 24858990
TI  - Association between erectile dysfunction and asymptomatic cardiovascular damage
      in middle-aged men.
AB  - BACKGROUND AND OBJECTIVE: It has been proposed that the same cardiovascular risk
      (CV) factors predispose middle-aged men to the development of both coronary
      artery disease and erectile dysfunction (ED). Moreover, several recently
      published studies have identified ED as a possible early marker of CV disease.
      The aim of this particular study was to evaluate the association between ED and
      early asymptomatic heart and vascular damage in middle-aged men with CV risk
      factors. MATERIAL AND METHODS: In this case-control study, the International
      Index of Erectile Function (IIEF) questionnaire was employed to assess the
      erectile function of the study participants and to allocate them either into the
      ED group (N=21; mean IIEF score, 18.15 [SD, 2.54]; mean age, 48.2 years [SD,
      4.4]) or the control group (N=24; mean IIEF score, 23.45 [SD, 0.99]; mean age,
      46.8 years [SD, 3.1]). Additionally, pulse wave velocity, augmentation index,
      pulse pressure, carotid intima media thickness (IMT), and atherosclerotic plaque
      count were determined, and echocardiography was performed in every subject.
      RESULTS: The mean IMT and left ventricular mass index (LVMI) of both carotid
      arteries in the ED group were significantly higher when compared with controls
      (598.57 vs. 535.54 mm.10(-3), P=0.03, and 107.26 vs. 98.67 g/m2, P=0.04,
      respectively). Using multiple regression analysis, an independent association
      between the IIEF score and the LVMI was found (P=0.002). No significant
      differences in the results of pulse wave velocity, atherosclerotic plaque count,
      and other laboratory tests were found between the 2 study groups. CONCLUSIONS:
      The study suggests that ED is associated with a higher LVMI and may be an early
      marker of CV disease.

PMID- 24858991
TI  - The frequency of CYP2C9, VKORC1, and CYP4F2 polymorphisms in Russian patients
      with high thrombotic risk.
AB  - BACKGROUND AND OBJECTIVE: VKORC1, CYP2C9, and CYP4F2 are known to be responsible
      for the metabolism of warfarin. The aim was to explore the frequencies of these
      genotypes in the Russian population and compare the results with those for other
      populations. MATERIAL AND METHODS: In total, 91 Caucasian subjects with a mean
      age of 66.17 years (SD, 10.9) were recruited into the study. Of them, 40 patients
      (48.2%) were men. In order to obtain necessary clinical data, the medical records
      of the patients were reviewed. Blood (5 mL) was taken from each subject, and DNA
      was isolated and used for identification of the CYP2C9 allele *1, *2, *3, 
      1639G/A VKORC1, and CYP4F2 V433M rs2108622 C>T, using the real-time polymerase
      chain reaction-restriction fragment length polymorphism assay. RESULTS: The
      CYP2C9*1/*1 genotype was detected in 67.0%, CYP2C9*1/*2 in 9.9%, CYP2C9*1/*3 in
      11.0%, CYP2C9*2/*2 in 2.2%, CYP2C9*2/*3 in 8.8%, and CYP2C9*3/*3 in 1.1% of the
      patients. The results for VKORC1 were as follows: 49.5% (GG), 28.6% (GA), and
      22.0% (AA); meanwhile, those for the genotype CYP4F2 were 57.1% (CC), 34.1% (CT),
      and 7.7% (TT). No significant deviations from the Hardy-Weinberg equilibrium were
      observed. The frequency of the polymorphisms in the Russian population was found
      to differ from Asian and close to Caucasian. There were no significant
      interethnic variations in the frequency of CYP4F2 among Russian, Asian, and
      Caucasian populations. CONCLUSION: The frequency of CYP2C9, CYP4F2, and VKORC1
      polymorphisms in Russian patients is comparable with other European ethnic
      groups.

PMID- 24858992
TI  - Resources of residents for potential transition from long-term care to community.
AB  - BACKGROUND AND OBJECTIVE: Transition from long-term care to the community can
      have positive effects on residents' health and quality of life and promote the
      feelings of happiness, safety, and independence. The aim of this study was to
      examine residents' resources for potential transition to the community after
      residing in long-term care facilities. MATERIAL AND METHODS: The study was
      conducted in 8 long-term care institutions for older persons of Kaunas county.
      The study population comprised 252 residents. The items contained in the interRAI
      Long-Term Care Facility assessment instrument were used to evaluate a consistent
      positive outlook, social activities, and discharge potential. Cognitive
      impairment was measured using the Cognitive Performance Scale. Activities of
      daily living were measured using the Activities of Daily Living Hierarchy Scale.
      RESULTS: More than 10% of the residents exhibited no cognitive impairment. One
      third of the residents preferred to transition back to the community from their
      long-term care facility. Two-thirds expressed that they had familiar
      surroundings, which could be assumed to increase their feeling of safety at home.
      Social activities prevalent among residents included taking care of plants and
      walking outdoors. About 40% of the residents were physically independent in the
      activities of daily living. In spite of these resources, no residents were
      involved in a discharge process due to the lack of established nursing and social
      care services and transitional care plans. CONCLUSIONS: With well-organized
      community services, some residents in long-term care facilities may have enough
      resources to live in the community.

PMID- 24858994
TI  - Outcome of the first successful heart-lung transplantation in the Baltic
      countries.
AB  - Successful heart-lung complex transplantation was performed in a 48-year-old man.
      During the postoperative period, M. tuberculosis infection was diagnosed, and the
      treatment subsequently started. One year after, the patient was urgently
      hospitalized due to myocardial infarction. However, despite the best efforts, the
      patient died. Antituberculosis treatment is recommended to all the patients with
      confirmed active tuberculosis. Treatment of tuberculosis in transplant recipients
      is similar to that of the general population, with the exclusion of rifamycins in
      the regimen and longer duration of treatment. 

PMID- 24858993
TI  - Increased use of antidepressants in Wuhan, China: a retrospective study from 2006
      to 2012.
AB  - OBJECTIVE: The aim of this study was to investigate the trend of antidepressant
      use and analyze the daily cost of antidepressants in Wuhan, China. MATERIAL AND
      METHODS: The data on the expenditure of antidepressants in Wuhan from 2006 to
      2012 were retrospectively analyzed based on the defined daily dose (DDD) method
      recommended by the World Health Organization. In addition, the daily cost of
      antidepressants was calculated for the pharmacoeconomic evaluation. RESULTS: The
      overall sales of antidepressants increased by 566.7% over the 7-year period. The
      utilization of antidepressants increased annually from 1.067 DDDs per 1000
      inhabitants per day in 2006 to 4.144 in 2012. This upward trend was mainly driven
      by an increase in the use of selective serotonin reuptake inhibitors (SSRIs),
      which accounted for about 60% of antidepressant use. Notably, the use of
      traditional Chinese patent medicines (TCMs) approved to treat depression in China
      in 2010 increased from 0.158 DDDs per 1000 inhabitants per day in 2010 to 0.305
      in 2012. The daily drug cost analysis indicated that selective serotonin and
      norepinephrine reuptake inhibitors (SNRIs) and other new antidepressants were
      more expensive while tricyclic and tetracyclic antidepressants (TCAs) had a low
      cost advantage. CONCLUSIONS: Antidepressants were increasingly used over the
      study period. Among them, SSRIs followed by SNRIs were the most commonly used.
      After the approval for the treatment of depression, TCMs were generally accepted
      by physicians and patients. The low-cost advantage allowed TCAs to be used in the
      antidepressant therapy.

PMID- 24858995
TI  - Detection of vascular endothelial growth factor based on rolling circle
      amplification as a means of signal enhancement in surface plasmon resonance.
AB  - Vascular endothelial growth factor (VEGF) is a major regulator of angiogenesis.
      It has been identified as an ideal biomarker for staging of many kinds of
      cancers, so more specific and intense signal is desirable for VEGF biosensors so
      that the sensors may have more valuable clinical application. Herein, we report a
      highly sensitive and selective surface plasmon resonance (SPR) sensor for VEGF
      detection by using two DNA aptamers which target different VEGF domains used as
      the capture and detection probe, respectively. Moreover, by making use of
      carboxyl-coated polystyrene microspheres, 3'-NH2 immobilized aptamer and 3'-NH2
      modified primer DNA are loaded through amidation onto the sensing layer for
      further rolling circle amplification (RCA) process to amplify the SPR signal.
      With the well-designed sensing platform, VEGF can be determined in a linear range
      from 100 pg mL(-1) to 1 MUg mL(-1) with a detection limit of 100 pg mL(-1). Due
      to its high specificity and desirable sensitivity, this RCA assisted SPR method
      may be a useful tool for the assay of VEGF in the future. What is more, by
      replacing the sensing element, i.e., the aptamer of VEGF used in this work, more
      biosensors for sensitive detection of other biomarkers proteins can be fabricated
      based on the strategy proposed in this study.

PMID- 24858996
TI  - Using protein-encapsulated gold nanoclusters as photoluminescent sensing probes
      for biomolecules.
AB  - In this study, we generated gold nanoclusters (AuNCs) using inexpensive chicken
      egg white proteins (AuNCs@ew) as reagents. AuNCs@ew were generated by reacting
      aqueous tetrachloroauric acid with diluted chicken egg white under microwave
      heating (90W) through subsequent heating cycles (5 min/cycle). Within 10 cycles,
      red photoluminescent AuNCs@ew with maximum emission wavelength at ~640 nm
      (lambdaex=370 nm) were obtained. The quantum yield of the as-generated AuNCs was
      ~6.6%. The intact and the tryptic digest of AuNCs@ew were characterized by mass
      spectrometry. The results showed that the AuNCs@ew were mainly derived from
      ovalbumin, i.e., the major protein in egg white, encapsulated AuNCs. The AuNCs@ew
      also has the common features found in AuNCs@protein, which is sensitive to the
      presence of heavy metal ions such as Cu(2+). The photoluminescence of the
      AuNCs@ew was quenched with the addition of Cu(2+). Furthermore, the
      photoluminescence of the quenched AuNCs@ew can be restored in the presence of the
      molecules containing phosphate functional groups because of the strong binding
      affinity between Cu(2+) and phosphates. We used the AuNCs@ew-Cu(2+) conjugates as
      switch-on sensing probes for the detection of phosphate containing metabolites
      such as adenosine-5'-triphosphate (ATP) and pyrophosphate (PPi). The results
      showed that the photoluminescence of the sensing probes increased as the
      concentration of the phosphate-containing molecules in the sample solution
      increased. The limits of detection achieved using the AuNCs@ew-Cu(2+) for ATP and
      PPi were ~19 and ~5 MUM, respectively. Additionally, we also demonstrated the
      feasibility of using the AuNCs@ew as the sensing probes for lectins such as
      concanavalin A (Con A) based on the molecular recognitions between the glycan
      ligands on the AuNCs@ew and glycan binding sites on Con A.

PMID- 24858997
TI  - An enhanced LSPR fiber-optic nanoprobe for ultrasensitive detection of protein
      biomarkers.
AB  - A miniaturized, localized surface plasmon resonance (LSPR)-coupled fiber-optic
      (FO) nanoprobe is reported as a biosensor that is capable of label-free,
      sensitive detection of a cancer protein biomarker, free prostate specific antigen
      (f-PSA). The biosensor is based on the LSPR at the reusable dielectric-metallic
      hybrid interface with a robust, gold nano-disk array at the fiber end facet that
      is directly fabricated using EBL and metal lift-off process. The f-PSA has been
      detected with a mouse anti-human PSA monoclonal antibody (mAb) as a specific
      receptor linked with a self-assembled monolayer at the LSPR-FO facet surfaces.
      Experimental investigation and data analysis found near field refractive index
      (RI) sensitivity at ~226 nm/RIU with current LSPR-FO nanoprobe, and demonstrated
      the lowest limit of detection (LOD) at 100 fg/mL (~3 fM) of f-PSA in PBS
      solutions. The control experimentation using 5mg/mL bovine serum albumin in PBS
      and nonspecific surface test shows the excellent specificity and selectivity in
      the detection of f-PSA in PBS. These results present important progress towards a
      miniaturized, multifunctional fiber-optic technology that integrates
      informational communication and sensing function for developing a high
      performance, label-free, point-of-care (POC) device.

PMID- 24858998
TI  - Curcumin suppresses cell proliferation through inhibition of the Wnt/beta-catenin
      signaling pathway in medulloblastoma.
AB  - Recently, the survival rate of medulloblastoma patients has greatly improved;
      yet, patients undergoing current treatment regimes suffer from serious therapy
      related side-effects. The aim of the present study was to investigate the
      anticancer effects of curcumin on medulloblastoma cells by testing its capacity
      to suppress proliferation and regulate the Wnt/beta-catenin pathway. In the
      present study, cell proliferation was determined by MTT assay. Cell cycle was
      observed by flow cytometry. The changes in the Wnt/beta-catenin pathway were
      analyzed by immunofluorescence, western blot analysis and RT-PCR. Curcumin
      treatment resulted in a dose- and time-dependent inhibition of proliferation in
      the medulloblastoma cell line. Curcumin treatment arrested the cell-cycle at the
      G2/M phase. Furthermore, curcumin treatment led to activation of GSK-3beta,
      reduced expression of beta-catenin and its downstream target cyclin D1. The
      attenuation of the Wnt/beta-catenin pathway was due to the loss of nuclear beta
      catenin. In conclusion, curcumin can inhibit cell growth by suppressing the
      Wnt/beta-catenin signaling pathway, and it has the potential to be developed as a
      therapeutic agent for medulloblastoma.

PMID- 24858999
TI  - Analysis of late-onset ovarian insufficiency after ovarian surgery: retrospective
      study with 75 patients of post-surgical ovarian insufficiency.
AB  - The primary objectives of the present study are to determine the period of onset
      of ovarian insufficiency after surgery and to confirm potential risk factors for
      ovarian insufficiency after surgery for the removal of benign ovarian cysts. Data
      were obtained from 75 patients who underwent surgery for benign ovarian cysts
      prior to the onset of ovarian insufficiency. Our analysis included 835 ovarian
      insufficiency patients who were referred to our institution from July 2003 to
      July 2013. Several epidemiological parameters of ovarian insufficiency after
      surgery (age at operation, period of onset of ovarian insufficiency, operation
      procedure, and pathological diagnosis) were investigated. Of the 835 patients who
      had ovarian insufficiency, 75 patients (9.0%) underwent ovarian surgery before
      the onset of ovarian insufficiency. Of those 75 patients, 66 patients (88.0%)
      underwent cystectomy. For the majority of the 75 patients the surgical indication
      was the presence of endometriotic cysts (57 patients; 76.0%). Twelve patients
      (16.0%) underwent multiple surgeries (all bilateral cystectomies). The mean age
      of the patients at the time of surgery was 27.8+/-5.5 years-old, and the mean
      period of onset of ovarian insufficiency was 5.8+/-3.8 years. In patients with
      cystectomy, the patient's age at the time of surgery and period of onset of
      ovarian insufficiency was well-correlated (coefficient of correlation;
      hemilateral endometriotic cystectomy: -0.64, bilateral endometriotic cystectomy: 
      0.61, and multiple endimetriotic cystectomy: -0.40). We found that cystectomy of
      endometriotic cysts is the potential risk factor for ovarian insufficiency after
      surgery, at times, the onset of ovarian insufficiency long after cystectomy.
      Therefore, it is important to monitor ovarian reserve for an extended period of
      time after ovarian surgery. It is particularly important to monitor ovarian
      reserve long-term for patients who wish to conceive in the future and to suggest
      a variety of infertility treatments appropriate for their ovarian reserve. 

PMID- 24859000
TI  - Use of dried blood spots for the determination of serum concentrations of
      tamoxifen and endoxifen.
AB  - The anti-estrogenic effect of tamoxifen is suggested to be mainly attributable to
      its metabolite (Z)-endoxifen, and a minimum therapeutic threshold for (Z)
      endoxifen in serum has been proposed. The objective of this research was to
      establish the relationship between dried blood spot (DBS) and serum
      concentrations of tamoxifen and (Z)-endoxifen to allow the use of DBS sampling, a
      simple and patient-friendly alternative to venous sampling, in clinical practice.
      Paired DBS and serum samples were obtained from 50 patients using tamoxifen and
      analyzed using HPLC-MS/MS. Serum concentrations were calculated from DBS
      concentrations using the formula calculated serum concentration = DBS
      concentration/([1-haematocrit (Hct)] + blood cell-to-serum ratio * Hct). The
      blood cell-to-serum ratio was determined ex vivo by incubating a batch of whole
      blood spiked with both analytes. The average Hct for female adults was imputed as
      a fixed value. Calculated and analyzed serum concentrations were compared using
      weighted Deming regression. Weighted Deming regression analysis comparing 44
      matching pairs of DBS and serum samples showed a proportional bias for both
      analytes. Serum concentrations were calculated using [Tamoxifen] serum,
      calculated  = [Tamoxifen] DBS /0.779 and [(Z)-Endoxifen] serum, calculated = [(Z)
      Endoxifen] DBS /0.663. Calculated serum concentrations were within 20 % of
      analyzed serum concentrations in 84 and 100 % of patient samples for tamoxifen
      and (Z)-endoxifen, respectively. In conclusion, DBS concentrations of tamoxifen
      and (Z)-endoxifen were equal to serum concentrations after correction for Hct and
      blood cell-to-serum ratio. DBS sampling can be used in clinical practice. 

PMID- 24859001
TI  - Initial characterization of the FlgE hook high molecular weight complex of
      Borrelia burgdorferi.
AB  - The spirochete periplasmic flagellum has many unique attributes. One unusual
      characteristic is the flagellar hook. This structure serves as a universal joint
      coupling rotation of the membrane-bound motor to the flagellar filament. The hook
      is comprised of about 120 FlgE monomers, and in most bacteria these structures
      readily dissociate to monomers (~ 50 kDa) when treated with heat and detergent.
      However, in spirochetes the FlgE monomers form a large mass of over 250 kDa
      [referred to as a high molecular weight complex (HMWC)] that is stable to these
      and other denaturing conditions. In this communication, we examined specific
      aspects with respect to the formation and structure of this complex. We found
      that the Lyme disease spirochete Borrelia burgdorferi synthesized the HMWC
      throughout the in vitro growth cycle, and also in vivo when implanted in dialysis
      membrane chambers in rats. The HMWC was stable to formic acid, which supports the
      concept that the stability of the HMWC is dependent on covalent cross-linking of
      individual FlgE subunits. Mass spectrometry analysis of the HMWC from both wild
      type periplasmic flagella and polyhooks from a newly constructed DeltafliK mutant
      indicated that other proteins besides FlgE were not covalently joined to the
      complex, and that FlgE was the sole component of the complex. In addition, mass
      spectrometry analysis also indicated that the HMWC was composed of a polymer of
      the FlgE protein with both the N- and C-terminal regions remaining intact. These
      initial studies set the stage for a detailed characterization of the HMWC.
      Covalent cross-linking of FlgE with the accompanying formation of the HMWC we
      propose strengthens the hook structure for optimal spirochete motility. 

PMID- 24859002
TI  - A Trio-Rac1-Pak1 signalling axis drives invadopodia disassembly.
AB  - Rho family GTPases control cell migration and participate in the regulation of
      cancer metastasis. Invadopodia, associated with invasive tumour cells, are
      crucial for cellular invasion and metastasis. To study Rac1 GTPase in invadopodia
      dynamics, we developed a genetically encoded, single-chain Rac1 fluorescence
      resonance energy (FRET) transfer biosensor. The biosensor shows Rac1 activity
      exclusion from the core of invadopodia, and higher activity when invadopodia
      disappear, suggesting that reduced Rac1 activity is necessary for their
      stability, and Rac1 activation is involved in disassembly. Photoactivating Rac1
      at invadopodia confirmed this previously unknown Rac1 function. We describe here
      an invadopodia disassembly model, where a signalling axis involving TrioGEF,
      Rac1, Pak1, and phosphorylation of cortactin, causes invadopodia dissolution.
      This mechanism is critical for the proper turnover of invasive structures during
      tumour cell invasion, where a balance of proteolytic activity and locomotory
      protrusions must be carefully coordinated to achieve a maximally invasive
      phenotype. 

PMID- 24859003
TI  - Actin dynamics modulate mechanosensitive immobilization of E-cadherin at adherens
      junctions.
AB  - Mechanical stress is increasingly being shown to be a potent modulator of cell
      cell junctional morphologies in developmental and homeostatic processes.
      Intercellular force sensing is thus expected to be an important regulator of cell
      signalling and tissue integrity. In particular, the interplay between myosin
      contractility, actin dynamics and E-cadherin recruitment largely remains to be
      uncovered. We devised a suspended cell doublet assay to quantitatively assess the
      correlation between myosin II activity and local E-cadherin recruitment. The
      single junction of the doublet exhibited a stereotypical morphology, with E
      cadherin accumulating into clusters of varied concentrations at the rim of the
      circular contact. This local recruitment into clusters derived from the
      sequestration of E-cadherin through a myosin-II-driven modulation of actin
      turnover. We exemplify how the regulation of actin dynamics provides a mechanism
      for the mechanosensitive response of cell contacts. 

PMID- 24859004
TI  - The ability of inner-cell-mass cells to self-renew as embryonic stem cells is
      acquired following epiblast specification.
AB  - The precise relationship of embryonic stem cells (ESCs) to cells in the mouse
      embryo remains controversial. We present transcriptional and functional data to
      identify the embryonic counterpart of ESCs. Marker profiling shows that ESCs are
      distinct from early inner cell mass (ICM) and closely resemble pre-implantation
      epiblast. A characteristic feature of mouse ESCs is propagation without ERK
      signalling. Single-cell culture reveals that cell-autonomous capacity to thrive
      when the ERK pathway is inhibited arises late during blastocyst development and
      is lost after implantation. The frequency of deriving clonal ESC lines suggests
      that all E4.5 epiblast cells can become ESCs. We further show that ICM cells from
      early blastocysts can progress to ERK independence if provided with a specific
      laminin substrate. These findings suggest that formation of the epiblast
      coincides with competence for ERK-independent self-renewal in vitro and
      consequent propagation as ESC lines. 

PMID- 24859006
TI  - The Par3-like polarity protein Par3L is essential for mammary stem cell
      maintenance.
AB  - The Par polarity proteins play key roles in asymmetric division of Drosophila
      melanogaster stem cells; however, whether the same mechanisms control stem cells
      in mammals is controversial. Although necessary for mammary gland morphogenesis,
      Par3 is not essential for mammary stem cell function. We discovered that,
      instead, a previously uncharacterized protein, Par3-like (Par3L), is vital for
      mammary gland stem cell maintenance. Par3L function has been mysterious because,
      unlike Par3, it does not interact with atypical protein kinase C or the Par6
      polarity protein. We found that Par3L is expressed by multipotent stem cells in
      the terminal end buds of murine mammary glands. Ablation of Par3L resulted in
      rapid and profound stem cell loss. Unexpectedly, Par3L, but not Par3, binds to
      the tumour suppressor protein Lkb1 and inhibits its kinase activity. This
      interaction is key for the function of Par3L in mammary stem cell maintenance.
      Our data reveal insights into a link between cell polarity proteins and stem cell
      survival, and uncover a biological function for Par3L.

PMID- 24859007
TI  - Particle swarm optimization with scale-free interactions.
AB  - The particle swarm optimization (PSO) algorithm, in which individuals collaborate
      with their interacted neighbors like bird flocking to search for the optima, has
      been successfully applied in a wide range of fields pertaining to searching and
      convergence. Here we employ the scale-free network to represent the inter
      individual interactions in the population, named SF-PSO. In contrast to the
      traditional PSO with fully-connected topology or regular topology, the scale-free
      topology used in SF-PSO incorporates the diversity of individuals in searching
      and information dissemination ability, leading to a quite different optimization
      process. Systematic results with respect to several standard test functions
      demonstrate that SF-PSO gives rise to a better balance between the convergence
      speed and the optimum quality, accounting for its much better performance than
      that of the traditional PSO algorithms. We further explore the dynamical
      searching process microscopically, finding that the cooperation of hub nodes and
      non-hub nodes play a crucial role in optimizing the convergence process. Our work
      may have implications in computational intelligence and complex networks. 

PMID- 24859005
TI  - CLASPs link focal-adhesion-associated microtubule capture to localized exocytosis
      and adhesion site turnover.
AB  - Turnover of integrin-based focal adhesions (FAs) with the extracellular matrix
      (ECM) is essential for coordinated cell movement. In collectively migrating human
      keratinocytes, FAs assemble near the leading edge, grow and mature as a result of
      contractile forces and disassemble underneath the advancing cell body. We report
      that clustering of microtubule-associated CLASP1 and CLASP2 proteins around FAs
      temporally correlates with FA turnover. CLASPs and LL5beta (also known as
      PHLDB2), which recruits CLASPs to FAs, facilitate FA disassembly. CLASPs are
      further required for FA-associated ECM degradation, and matrix metalloprotease
      inhibition slows FA disassembly similarly to CLASP or PHLDB2 (LL5beta) depletion.
      Finally, CLASP-mediated microtubule tethering at FAs establishes an FA-directed
      transport pathway for delivery, docking and localized fusion of exocytic vesicles
      near FAs. We propose that CLASPs couple microtubule organization, vesicle
      transport and cell interactions with the ECM, establishing a local secretion
      pathway that facilitates FA turnover by severing cell-matrix connections. 

PMID- 24859009
TI  - Discrepancy between species borders at morphological and molecular levels in the
      genus Cochliopodium (Amoebozoa, Himatismenida), with the description of
      Cochliopodium plurinucleolum n. sp.
AB  - Amoebae of the genus Cochliopodium are characterized by a tectum that is a layer
      of scales covering the dorsal surface of the cell. A combination of scale
      structure, morphological features and, nowadays, molecular information allows
      species discrimination. Here we describe a soil species Cochliopodium
      plurinucleolum n. sp. that besides strong genetic divergence from all currently
      described species of Cochliopodium differs morphologically by the presence of
      several peripheral nucleoli in the nucleus. Further, we unambiguously show that
      the Golgi attachment associated with a dictyosome in Cochliopodium is a
      cytoplasmic microtubule organizing center (MTOC). Last, we provide detailed
      morphological and molecular information on the sister clade of C. plurinucleolum,
      containing C. minus, C. minutoidum, C. pentatrifurcatum and C. megatetrastylus.
      These species share nearly identical sequences of both, small subunit ribosomal
      RNA and partial Cox1 genes, and nearly identical structure of the scales. Scales
      of C. pentatrifurcatum differ, however, strongly from scales of the others while
      sequences of C. pentatrifurcatum and C. minus are nearly identical. These
      discrepancies urge for future sampling efforts to disentangle species
      characteristics within Cochliopdium and to investigate morphological and
      molecular patterns that allow reliable species differentiation. 

PMID- 24859008
TI  - I-BET151 selectively regulates IL-6 production.
AB  - Orchestration of the inflammatory response is crucial for clearing pathogens.
      Although the production of multiple inflammatory cytokines has been thought to be
      regulated by common mechanisms, recent evidence indicates that the expression of
      some cytokines is differentially regulated by epigenetic regulatory mechanisms.
      In this study, we found that IL-6 production is selectively inhibited by the BET
      bromodomain protein (BRD) inhibitor I-BET151 in RAW264.7 cells stimulated with
      lipopolysaccharide (LPS), whereas I-BET151 did not alter the production of
      several other cytokines (TNFalpha, IL-1beta and IL-10) at the concentration of
      IBET151 used. I-BET151 prevented the binding of CBP to the promoter of IL-6, but
      I-BET151 did not affect acetylation, phosphorylation, nuclear translocation, or
      DNA binding of p65-NF-kappaB. In vivo, I-BET151 treatment in the experimental
      autoimmune encephalomyelitis mouse model of multiple sclerosis decreased the
      early clinical symptoms, which are thought to be dependent on cytokine
      production. Altogether, these data suggest that targeting epigenetic-related
      proteins, such as BET proteins, may provide a strategy to reduce inflammation and
      the severity of inflammatory diseases, such as multiple sclerosis. 

PMID- 24859010
TI  - Factors associated with pregnancy attempts among female young adult cancer
      survivors.
AB  - PURPOSE: Little is known about pregnancy attempts among female young cancer
      survivors (YCS). We sought to determine fertility preservation (FP), demographic,
      cancer, and reproductive characteristics associated with pregnancy attempts after
      cancer. METHODS: We recruited 251 female YCS (ages 18-44) to complete a survey on
      reproductive health outcomes. We used log-binomial regression models to estimate
      relative risks (RR) for characteristics associated with pregnancy attempts.
      RESULTS: For the entire cohort, median time since cancer diagnosis was 2.4 years
      (interquartile range 4.0). Fifty-two YCS (21%) attempted pregnancy after cancer
      diagnosis. In unadjusted analyses, lack of FP therapy prior to cancer treatment,
      older age, partnered relationship, higher income, no history of stem cell or bone
      marrow transplant, and longer duration of survivorship were significantly
      associated with pregnancy attempts. In multivariable analyses, YCS who did not
      undergo FP therapy were more than twice as likely to attempt pregnancy as those
      who did undergo FP therapy (RR 2.4, 95% confidence interval (CI) 1.3, 4.3).
      Partnered status (RR 7.1, 95% CI 2.5, 20.2) and >2 years since cancer diagnosis
      (RR 2.3, 95% CI 1.3, 4.1) were also significantly associated with attempts.
      CONCLUSIONS: In YCS, milestones including partnered relationships and longer
      duration of cancer survivorship are important to attempting pregnancy. A novel,
      inverse association between FP therapy and pregnancy attempts warrants further
      study. IMPLICATIONS FOR CANCER SURVIVORS: Pregnancy attempts after cancer were
      more likely after attaining both social- and cancer-related milestones. As these
      milestones require time, YCS should be made aware of their potential for
      concomitant, premature loss of fertility in order to preserve their range of
      fertility options.

PMID- 24859011
TI  - Genome-wide identification, characterisation and expression analysis of the MADS
      box gene family in Prunus mume.
AB  - MADS-box genes encode transcription factors that play crucial roles in plant
      development, especially in flower and fruit development. To gain insight into
      this gene family in Prunus mume, an important ornamental and fruit plant in East
      Asia, and to elucidate their roles in flower organ determination and fruit
      development, we performed a genome-wide identification, characterisation and
      expression analysis of MADS-box genes in this Rosaceae tree. In this study, 80
      MADS-box genes were identified in P. mume and categorised into MIKC, Malpha,
      Mbeta, Mgamma and Mdelta groups based on gene structures and phylogenetic
      relationships. The MIKC group could be further classified into 12 subfamilies.
      The FLC subfamily was absent in P. mume and the six tandemly arranged DAM genes
      might experience a species-specific evolution process in P. mume. The MADS-box
      gene family might experience an evolution process from MIKC genes to Mdelta genes
      to Malpha, Mbeta and Mgamma genes. The expression analysis suggests that P. mume
      MADS-box genes have diverse functions in P. mume development and the functions of
      duplicated genes diverged after the duplication events. In addition to its
      involvement in the development of female gametophytes, type I genes also play
      roles in male gametophytes development. In conclusion, this study adds to our
      understanding of the roles that the MADS-box genes played in flower and fruit
      development and lays a foundation for selecting candidate genes for functional
      studies in P. mume and other species. Furthermore, this study also provides a
      basis to study the evolution of the MADS-box family. 

PMID- 24859012
TI  - Expansion of NK cells by engineered K562 cells co-expressing 4-1BBL and mMICA,
      combined with soluble IL-21.
AB  - NK cells hold promise for protecting hosts from cancer and pathogen infection
      through direct killing and expressing immune-regulatory cytokines. In our study,
      a genetically modified K562 cell line with surface expression of 4-1BBL and MICA
      was constructed to expand functional NK cells in vitro for further adoptive
      immunotherapy against cancer. After a long-term up to 21 day co-culture with
      newly isolated peripheral blood mononuclear cells (PBMCs) in the presence of
      soluble IL-21 (sIL-21), notable increase in proportion of expanded NK cells was
      observed, especially the CD56(bright)CD16(+) subset. Apparent up-regulation of
      activating receptors CD38, CD69 and NKG2D was detected on expanded NK cells, so
      did inhibitory receptor CD94; the cytotoxicity of expanded NK cells against
      target tumor cells exceeded that of NK cells within fresh PBMCs. The
      intracellular staining showed expanded NK cells produced immune-regulatory IFN
      gamma. Taken together, we expanded NK cells with significant up-regulation of
      activating NKG2D and moderate enhancement of cytotoxicity, with IFN-gamma
      producing ability and a more heterogeneous population of NK cells. These findings
      provide a novel perspective on expanding NK cells in vitro for further biology
      study and adoptive immunotherapy of NK cells against cancer.

PMID- 24859013
TI  - Anti-inflammatory mechanism of alpha-viniferin regulates lipopolysaccharide
      induced release of proinflammatory mediators in BV2 microglial cells.
AB  - alpha-Viniferin is an oligostilbene of trimeric resveratrol and has anticancer
      activity; however, the molecular mechanism underlying the anti-inflammatory
      effects of alpha-viniferin has not been completely elucidated thus far.
      Therefore, we determined the mechanism by which alpha-viniferin regulates
      lipopolysaccharide (LPS)-induced expression of proinflammatory mediators in BV2
      microglial cells. Treatment with alpha-viniferin isolated from Clematis
      mandshurica decreased LPS-induced production of nitric oxide (NO) and
      prostaglandin E2 (PGE2). alpha-Viniferin also downregulated the LPS-induced
      expression of proinflammatory genes such as iNOS and COX-2 by suppressing the
      activity of nuclear factor kappa B (NF-kappaB) via dephosphorylation of Akt/PI3K.
      Treatment with a specific NF-kappaB inhibitor, pyrrolidine dithiocarbamate
      (PDTC), indirectly showed that NF-kappaB is a crucial transcription factor for
      expression of these genes in the early stage of inflammation. Additionally, our
      results indicated that alpha-viniferin suppresses NO and PGE2 production in the
      late stage of inflammation through induction of heme oxygenase-1 (HO-1) regulated
      by nuclear factor erythroid 2-related factor (Nrf2). Taken together, our data
      indicate that alpha-viniferin suppresses the expression of proinflammatory genes
      iNOS and COX-2 in the early stage of inflammation by inhibiting the Akt/PI3K
      dependent NF-kappaB activation and inhibits the production of proinflammatory
      mediators NO and PGE2 in the late stage by stimulating Nrf2-mediated HO-1
      signaling pathway in LPS-stimulated BV2 microglial cells. These results suggest
      that alpha-viniferin may be a potential candidate to regulate LPS-induced
      inflammation.

PMID- 24859014
TI  - Peroxynitrite modified DNA presents better epitopes for anti-DNA autoantibodies
      in diabetes type 1 patients.
AB  - Peroxynitrite (ONOO(-)), formed by the reaction between nitric oxide (NO) and
      superoxide (O2(-)), has been implicated in the etiology of numerous disease
      processes. Peroxynitrite interacts with DNA via direct oxidative reactions or via
      indirect radical-mediated mechanism. It can inflict both oxidative and
      nitrosative damages on DNA bases, generating abasic sites, resulting in the
      single strand breaks. Plasmid pUC 18 isolated from Escherichiacoli was modified
      with peroxynitrite, generated by quenched flow process. Modifications incurred in
      plasmid DNA were characterized by ultraviolet and fluorescence spectroscopy,
      circular dichroism, HPLC and melting temperature studies. Binding characteristics
      and specificity of antibodies from diabetes patients were analyzed by direct
      binding and inhibition ELISA. Peroxynitrite modification of pUC 18 plasmid
      resulted in the formation of strand breaks and base modification. The major
      compound formed when peroxynitrite reacted with DNA was 8-nitroguanine, a
      specific marker for peroxynitrite induced DNA damage in inflamed tissues. The
      concentration of 8-nitroguanine was found to be 3.8 MUM. Sera from diabetes type
      1 patients from different age groups were studied for their binding to native and
      peroxynitrite modified plasmid. Direct binding and competitive-inhibition ELISA
      results showed higher recognition of peroxynitrite modified plasmid, as compared
      to the native form, by auto-antibodies present in diabetes patients. The
      preferential recognition of modified plasmid by diabetes autoantibodies was
      further reiterated by gel shift assay. Experimentally induced anti-peroxynitrite
      modified plasmid IgG was used as a probe to detect nitrosative lesions in the DNA
      isolated from diabetes patients.

PMID- 24859016
TI  - Local radiation dose and solid second malignant neoplasms after childhood cancer
      in Germany: a nested case-control study.
AB  - Radiotherapy (RT) has been associated with the development of solid second
      malignant neoplasms (SMNs) in childhood cancer survivors. The aim of this study
      was to analyse the effect of cumulative doses of previous RT received at the SMN
      body region, at all other body regions and at body regions adjacent to the SMN,
      on the risk of developing a solid SMN. A total of 190 cases diagnosed with a
      solid second malignant neoplasm in 1980-2002 were matched with 368 controls with
      single neoplasm from the database of the German Childhood Cancer Registry (GCCR)
      (33,809 patients at cut-off date). The GCCR registers approximately 97 % of all
      childhood malignancies which occur at an age of less than 15 years in Germany
      since 1980. It was found that 147 (77.4 %) cases had received RT compared to 208
      (56.6 %) controls with cumulative focus doses from 8 to 110 Gy. Fifty per cent of
      the SMNs and 60 % of RT affected the head region. RT was shown to increase the
      risk of a solid second tumour within the body region of radiation by 5.3 % per Gy
      (odds ratio 1.053; 95 % confidence interval 1.036-1.071). With increasing age at
      diagnosis and with more recent treatment eras, this effect decreased. Cumulative
      RT doses received at all other body regions or only at body regions adjacent to
      the SMN did not show an additional effect on the risk of developing an SMN. It is
      thus concluded that RT is the main risk factor for the development of SMNs within
      the irradiated body region. Late effects surveillance of former patients should
      give special attention to the originally irradiated parts of the body. 

PMID- 24859017
TI  - Pathogenesis of rheumatoid arthritis: from systemic autoimmunity to localised
      joint disease.

PMID- 24859015
TI  - Targeting of the MYCN protein with small molecule c-MYC inhibitors.
AB  - Members of the MYC family are the most frequently deregulated oncogenes in human
      cancer and are often correlated with aggressive disease and/or poorly
      differentiated tumors. Since patients with MYCN-amplified neuroblastoma have a
      poor prognosis, targeting MYCN using small molecule inhibitors could represent a
      promising therapeutic approach. We have previously demonstrated that the small
      molecule 10058-F4, known to bind to the c-MYC bHLHZip dimerization domain and
      inhibiting the c-MYC/MAX interaction, also interferes with the MYCN/MAX
      dimerization in vitro and imparts anti-tumorigenic effects in neuroblastoma tumor
      models with MYCN overexpression. Our previous work also revealed that MYCN
      inhibition leads to mitochondrial dysfunction resulting in accumulation of lipid
      droplets in neuroblastoma cells. To expand our understanding of how small
      molecules interfere with MYCN, we have now analyzed the direct binding of 10058
      F4, as well as three of its analogs; #474, #764 and 10058-F4(7RH), one metabolite
      C-m/z 232, and a structurally unrelated c-MYC inhibitor 10074-G5, to the bHLHZip
      domain of MYCN. We also assessed their ability to induce apoptosis, neurite
      outgrowth and lipid accumulation in neuroblastoma cells. Interestingly, all c-MYC
      binding molecules tested also bind MYCN as assayed by surface plasmon resonance.
      Using a proximity ligation assay, we found reduced interaction between MYCN and
      MAX after treatment with all molecules except for the 10058-F4 metabolite C-m/z
      232 and the non-binder 10058-F4(7RH). Importantly, 10074-G5 and 10058-F4 were the
      most efficient in inducing neuronal differentiation and lipid accumulation in
      MYCN-amplified neuroblastoma cells. Together our data demonstrate MYCN-binding
      properties for a selection of small molecules, and provide functional information
      that could be of importance for future development of targeted therapies against
      MYCN-amplified neuroblastoma. 

PMID- 24859018
TI  - Histamine H4 receptor antagonists for the treatment of inflammatory disorders.
AB  - Since its initial discovery by Sir Henry Dale and Patrick Laidlaw in 1910, the
      biogenic amine histamine has been one of the most widely researched molecules in
      science. H4R, the newest member of the histamine receptor family, was first
      identified at the turn of the millennium. Its predominant expression on
      inflammatory cells and lymphoid tissues, coupled with a key role in processes
      ranging from chemotaxis to cytokine release, suggests it could command an
      important role in immune and inflammatory responses. 

PMID- 24859019
TI  - Glucocorticoids induce apoptosis by inhibiting microRNA cluster miR-17-92
      expression in chondrocytic cells.
AB  - Sustained treatment with glucocorticoids (GCs) has frequently been observed to
      impair skeletal development. However, the influence of GCs on chondrocytes, which
      have a key role in skeletal development, has been rarely reported. HCS-2/8 cells
      were selected as an in vitro model of human chondrocytes to assess the apoptosis
      induced by GCs and determine the role of the microRNA-17-92 (miR-17-92) cluster
      in the regulation of apoptosis. It was demonstrated that dexamethasone (Dex) was
      able to induce apoptosis and high levels of expression of apoptosis-associated
      molecules in HCS-2/8 chondrocytic cells, and that expression of the miR-17-92
      cluster was inhibited during Dex-induced apoptosis. In conclusion, the present
      study suggested that inhibition of the expression of the miR-17-92 cluster
      contributed to the Dex-induced apoptosis in chondrocytes. The results suggest
      that microRNAs have an important role in glucocorticoid-induced impairment to
      chondrocytes. 

PMID- 24859020
TI  - A new chasmosaurine from northern Laramidia expands frill disparity in ceratopsid
      dinosaurs.
AB  - A new taxon of chasmosaurine ceratopsid demonstrates unexpected disparity in
      parietosquamosal frill shape among ceratopsid dinosaurs early in their
      evolutionary radiation. The new taxon is described based on two apomorphic
      squamosals collected from approximately time equivalent (approximately 77 million
      years old) sections of the upper Judith River Formation, Montana, and the lower
      Dinosaur Park Formation of Dinosaur Provincial Park, Alberta. It is referred to
      Chasmosaurinae based on the inferred elongate morphology. The typical
      chasmosaurine squamosal forms an obtuse triangle in dorsal view that tapers
      towards the posterolateral corner of the frill. In the dorsal view of the new
      taxon, the lateral margin of the squamosal is hatchet-shaped with the posterior
      portion modified into a constricted narrow bar that would have supported the
      lateral margin of a robust parietal. The new taxon represents the oldest
      chasmosaurine from Canada, and the first pre-Maastrichtian ceratopsid to have
      been collected on both sides of the Canada-US border, with a minimum north-south
      range of 380 km. This squamosal morphology would have given the frill of the new
      taxon a unique dorsal profile that represents evolutionary experimentation in
      frill signalling near the origin of chasmosaurine ceratopsids and reinforces
      biogeographic differences between northern and southern faunal provinces in the
      Campanian of North America.

PMID- 24859021
TI  - Clinical significance of measuring soluble LR11, a circulating marker of
      atherosclerosis and HbA1c in familial hypercholesterolemia.
AB  - OBJECTIVES: The LDL receptor relative with 11 ligand-binding repeats (LR11) is
      closely related to atherosclerotic disease or diabetes. The aim of the study was
      to clarify how soluble LR11 was related to Achilles' tendon thickness (ATT) and
      HbA1c in familial hypercholesterolemia. DESIGN AND METHODS: The present study is
      a cross-sectional case-control study. We enrolled twenty-four patients with
      heterozygous FH (age 51.0+/-20.0 year; male, 50%; 20 cases with LDL receptor
      mutation, 1 case with proprotein convertase subtilisin/kexin type 9 (PCSK9) E32K
      and 3 cases without confirmed mutations). Soluble LR11 (sLR11) was measured using
      a sandwich enzyme-linked immunosorbent assay method. RESULTS: Univariate
      regression analysis showed that sLR11 had positive correlations with age and
      HbA1c, and inverse correlations with apoA1 in FH. There were also positive
      correlations of sLR11 with apoE, IDL-C and average ATT. Multivariate regression
      analysis showed that there were positive correlations of sLR11 to IDL-C and HbA1c
      independent of age and BMI. In another multivariate regression analysis on the
      relationships of average ATT as a dependent variable with age, BMI and sLR11 (IDL
      C and HbA1c) as independent variables, sLR11 had a positive correlation with
      average ATT, independent of age and BMI. However, this independency did not
      persist after adding IDL-C and HbA1c as confounding factors. Of special note is
      that HbA1c showed a significant correlation with average ATT, independent of
      other parameters including sLR11. CONCLUSION: It is crucial to intervene in the
      existence of remnant lipoprotein as well as hypercholesterolemia from an early
      stage and conduct glycemic control to prevent the progression of atherosclerotic
      disease in FH.

PMID- 24859022
TI  - A compact immunoassay platform based on a multicapillary glass plate.
AB  - A highly sensitive, rapid immunoassay performed in the multi-channels of a micro
      well array consisting of a multicapillary glass plate (MCP) and a
      polydimethylsiloxane (PDMS) slide is described. The micro-dimensions and large
      surface area of the MCP permitted the diffusion distance to be decreased and the
      reaction efficiency to be increased. To confirm the concept of the method, human
      immunoglobulin A (h-IgA) was measured using both the proposed immunoassay system
      and the traditional 96-well plate method. The proposed method resulted in a 1/5
      fold decrease of immunoassay time, and a 1/56-fold cut in reagent consumption
      with a 0.05 ng/mL of limit of detection (LOD) for IgA. The method was also
      applied to saliva samples obtained from healthy volunteers. The results
      correlated well to those obtained by the 96-well plate method. The method has the
      potential for use in disease diagnostic or on-site immunoassays. 

PMID- 24859023
TI  - Discovery of Pantoea rodasii strain ND03 that produces N-(3-Oxo-hexanoyl)-L
      homoserine lactone.
AB  - Proteobacteria use quorum sensing to regulate target gene expression in response
      to population density. Quorum sensing (QS) is achieved via so-called signalling
      molecules and the best-studied QS signalling system uses N-acyl homoserine
      lactones (AHLs). This study aimed to identify and characterize the production of
      AHLs by a bacterium ND03 isolated from a Malaysian tropical rainforest waterfall.
      Molecular identification showed that ND03 is a Pantoea sp. closely related to
      Pantoea rodasii. We used Chromobacterium violaceum CV026, an AHL biosensor for
      preliminary AHL production screening and then used high resolution triple
      quadrupole liquid chromatography-mass spectrometry, to confirm that P. rodasii
      strain ND03 produced N-(3-oxo-hexanoyl)-L-homoserine lactone (3-oxo-C6-HSL). To
      the best of our knowledge, this is the first report for such a discovery in P.
      rodasii strain ND03. 

PMID- 24859024
TI  - Surveying wearable human assistive technology for life and safety critical
      applications: standards, challenges and opportunities.
AB  - In this survey a new application paradigm life and safety for critical operations
      and missions using wearable Wireless Body Area Networks (WBANs) technology is
      introduced. This paradigm has a vast scope of applications, including disaster
      management, worker safety in harsh environments such as roadside and building
      workers, mobile health monitoring, ambient assisted living and many more. It is
      often the case that during the critical operations and the target conditions, the
      existing infrastructure is either absent, damaged or overcrowded. In this
      context, it is envisioned that WBANs will enable the quick deployment of ad
      hoc/on-the-fly communication networks to help save many lives and ensuring
      people's safety. However, to understand the applications more deeply and their
      specific characteristics and requirements, this survey presents a comprehensive
      study on the applications scenarios, their context and specific requirements. It
      explores details of the key enabling standards, existing state-of-the-art
      research studies, and projects to understand their limitations before realizing
      aforementioned applications. Application-specific challenges and issues are
      discussed comprehensively from various perspectives and future research and
      development directions are highlighted as an inspiration for new innovative
      solutions. To conclude, this survey opens up a good opportunity for companies and
      research centers to investigate old but still new problems, in the realm of
      wearable technologies, which are increasingly evolving and getting more and more
      attention recently. 

PMID- 24859025
TI  - Comparative study on a solving model and algorithm for a flush air data sensing
      system.
AB  - With the development of high-performance aircraft, precise air data are necessary
      to complete challenging tasks such as flight maneuvering with large angles of
      attack and high speed. As a result, the flush air data sensing system (FADS) was
      developed to satisfy the stricter control demands. In this paper, comparative
      stuides on the solving model and algorithm for FADS are conducted. First, the
      basic principles of FADS are given to elucidate the nonlinear relations between
      the inputs and the outputs. Then, several different solving models and algorithms
      of FADS are provided to compute the air data, including the angle of attck,
      sideslip angle, dynamic pressure and static pressure. Afterwards, the evaluation
      criteria of the resulting models and algorithms are discussed to satisfy the real
      design demands. Futhermore, a simulation using these algorithms is performed to
      identify the properites of the distinct models and algorithms such as the
      measuring precision and real-time features. The advantages of these models and
      algorithms corresponding to the different flight conditions are also analyzed,
      furthermore, some suggestions on their engineering applications are proposed to
      help future research. 

PMID- 24859026
TI  - RESTful discovery and eventing for service provisioning in assisted living
      environments.
AB  - Service provisioning in assisted living environments faces distinct challenges
      due to the heterogeneity of networks, access technology, and sensing/actuation
      devices in such an environment. Existing solutions, such as SOAP-based web
      services, can interconnect heterogeneous devices and services, and can be
      published, discovered and invoked dynamically. However, it is considered heavier
      than what is required in the smart environment-like context and hence suffers
      from performance degradation. Alternatively, REpresentational State Transfer
      (REST) has gained much attention from the community and is considered as a
      lighter and cleaner technology compared to the SOAP-based web services. Since it
      is simple to publish and use a RESTful web service, more and more service
      providers are moving toward REST-based solutions, which promote a resource
      centric conceptualization as opposed to a service-centric conceptualization.
      Despite such benefits of REST, the dynamic discovery and eventing of RESTful
      services are yet considered a major hurdle to utilization of the full potential
      of REST-based approaches. In this paper, we address this issue, by providing a
      RESTful discovery and eventing specification and demonstrate it in an assisted
      living healthcare scenario. We envisage that through this approach, the service
      provisioning in ambient assisted living or other smart environment settings will
      be more efficient, timely, and less resource-intensive. 

PMID- 24859027
TI  - A low-power integrated humidity CMOS sensor by printing-on-chip technology.
AB  - A low-power, wide-dynamic-range integrated humidity sensing chip is implemented
      using a printable polymer sensing material with an on-chip pulse-width-modulation
      interface circuit. By using the inkjet printing technique, poly(3,4-ethylene
      dioxythiophene)/polystyrene sulfonate that has humidity sensing features can be
      printed onto the top metal layer of a 0.35 MUm CMOS IC. The developed printing-on
      chip humidity sensor achieves a heterogeneous three dimensional sensor system-on
      chip architecture. The humidity sensing of the implemented printing-on-chip
      sensor system is experimentally tested. The sensor shows a sensitivity of 0.98%
      to humidity in the atmosphere. The maximum dynamic range of the readout circuit
      is 9.8 MOmega, which can be further tuned by the frequency of input signal to fit
      the requirement of the resistance of printed sensor. The power consumption keeps
      only 154 MUW. This printing-on-chip sensor provides a practical solution to
      fulfill an ultra-small integrated sensor for the applications in miniaturized
      sensing systems. 

PMID- 24859028
TI  - A measuring system for well logging attitude and a method of sensor calibration.
AB  - This paper proposes an approach for measuring the azimuth angle and tilt angle of
      underground drilling tools with a MEMS three-axis accelerometer and a three-axis
      fluxgate sensor. A mathematical model of well logging attitude angle is deduced
      based on combining space coordinate transformations and algebraic equations. In
      addition, a system implementation plan of the inclinometer is given in this
      paper, which features low cost, small volume and integration. Aiming at the
      sensor and assembly errors, this paper analyses the sources of errors, and
      establishes two mathematical models of errors and calculates related parameters
      to achieve sensor calibration. The results show that this scheme can obtain a
      stable and high precision azimuth angle and tilt angle of drilling tools, with
      the deviation of the former less than +/-1.4 degrees  and the deviation of the
      latter less than +/-0.1 degrees . 

PMID- 24859029
TI  - MLAOS: a multi-point linear array of optical sensors for coniferous foliage
      clumping index measurement.
AB  - The canopy foliage clumping effect is primarily caused by the non-random
      distribution of canopy foliage. Currently, measurements of clumping index (CI) by
      handheld instruments is typically time- and labor-intensive. We propose a low
      cost and low-power automatic measurement system called Multi-point Linear Array
      of Optical Sensors (MLAOS), which consists of three above-canopy and nine below
      canopy optical sensors that capture plant transmittance at different times of the
      day. Data communication between the MLAOS node is facilitated by using a ZigBee
      network, and the data are transmitted from the field MLAOS to a remote data
      server using the Internet. The choice of the electronic element and design of the
      MLAOS software is aimed at reducing costs and power consumption. A power
      consumption test showed that, when a 4000 mAH Li-ion battery is used, a maximum
      of 8-10 months of work can be achieved. A field experiment on a coniferous forest
      revealed that the CI of MLAOS may reveal a clumping effect that occurs within the
      canopy. In further work, measurement of the multi-scale clumping effect can be
      achieved by utilizing a greater number of MLAOS devices to capture the
      heterogeneity of the plant canopy. 

PMID- 24859030
TI  - A new acquisition and imaging system for environmental measurements: an
      experience on the Italian cultural heritage.
AB  - A new acquisition system for remote control of wall paintings has been realized
      and tested in the field. The system measures temperature and atmospheric pressure
      in an archeological site where a fresco has been put under control. The measuring
      chain has been designed to be used in unfavorable environments where neither
      electric power nor telecommunication infrastructures are available. The
      environmental parameters obtained from the local monitoring are then transferred
      remotely allowing an easier management by experts in the field of conservation of
      cultural heritage. The local acquisition system uses an electronic card based on
      microcontrollers and sends the data to a central unit realized with a Raspberry
      Pi. The latter manages a high quality camera to pick up pictures of the fresco.
      Finally, to realize the remote control at a site not reached by internet signals,
      a WiMAX connection based on different communication technologies such as WiMAX,
      Ethernet, GPRS and Satellite, has been set up. 

PMID- 24859031
TI  - ATHENA: a personalized platform to promote an active lifestyle and wellbeing
      based on physical, mental and social health primitives.
AB  - Technology provides ample opportunities for the acquisition and processing of
      physical, mental and social health primitives. However, several challenges remain
      for researchers as how to define the relationship between reported physical
      activities, mood and social interaction to define an active lifestyle. We are
      conducting a project, ATHENA(activity-awareness for human-engaged wellness
      applications) to design and integrate the relationship between these basic health
      primitives to approximate the human lifestyle and real-time recommendations for
      wellbeing services. Our goal is to develop a system to promote an active
      lifestyle for individuals and to recommend to them valuable interventions by
      making comparisons to their past habits. The proposed system processes sensory
      data through our developed machine learning algorithms inside smart devices and
      utilizes cloud infrastructure to reduce the cost. We exploit big data
      infrastructure for massive sensory data storage and fast retrieval for
      recommendations. Our contributions include the development of a prototype system
      to promote an active lifestyle and a visual design capable of engaging users in
      the goal of increasing self-motivation. We believe that our study will impact the
      design of future ubiquitous wellness applications. 

PMID- 24859032
TI  - Dynamic Bayesian networks for context-aware fall risk assessment.
AB  - Fall incidents among the elderly often occur in the home and can cause serious
      injuries affecting their independent living. This paper presents an approach
      where data from wearable sensors integrated in a smart home environment is
      combined using a dynamic Bayesian network. The smart home environment provides
      contextual data, obtained from environmental sensors, and contributes to
      assessing a fall risk probability. The evaluation of the developed system is
      performed through simulation. Each time step is represented by a single user
      activity and interacts with a fall sensors located on a mobile device. A
      posterior probability is calculated for each recognized activity or contextual
      information. The output of the system provides a total risk assessment of falling
      given a response from the fall sensor. 

PMID- 24859033
TI  - Real-time algebraic derivative estimations using a novel low-cost architecture
      based on reconfigurable logic.
AB  - Time derivative estimation of signals plays a very important role in several
      fields, such as signal processing and control engineering, just to name a few of
      them. For that purpose, a non-asymptotic algebraic procedure for the approximate
      estimation of the system states is used in this work. The method is based on
      results from differential algebra and furnishes some general formulae for the
      time derivatives of a measurable signal in which two algebraic derivative
      estimators run simultaneously, but in an overlapping fashion. The algebraic
      derivative algorithm presented in this paper is computed online and in real-time,
      offering high robustness properties with regard to corrupting noises, versatility
      and ease of implementation. Besides, in this work, we introduce a novel
      architecture to accelerate this algebraic derivative estimator using
      reconfigurable logic. The core of the algorithm is implemented in an FPGA,
      improving the speed of the system and achieving real-time performance. Finally,
      this work proposes a low-cost platform for the integration of hardware in the
      loop in MATLAB. 

PMID- 24859034
TI  - Sex differences in the pharmacokinetics of antidepressants: influence of female
      sex hormones and oral contraceptives.
AB  - Women are twice as likely to develop depression as men. Moreover, the symptoms
      they experience also show sex differences: women tend to develop depression at an
      earlier age and show more severe symptoms than men. Likewise, the response to
      antidepressant pharmacotherapy appears to have sex differences. These differences
      can partially be explained by differences in pharmacokinetic properties (i.e.,
      absorption, distribution, metabolism, and excretion) of drugs in males and
      females. More recent research has shown that sex hormones may influence all these
      previously named pharmacokinetic processes. As concentrations of sex hormones
      vary throughout the female lifespan, these hormonal variations can have effects
      on therapeutic responses to antidepressants as well as the occurrence of adverse
      events. The purpose of this paper is therefore to review the literature reporting
      on the effects of female sex hormones on the pharmacokinetics of antidepressants
      and to discuss and evaluate the implications of changes in levels of sex hormones
      throughout life for the treatment of depression.

PMID- 24859036
TI  - Assessing the invariance of a culturally competent multi-lingual unmet needs
      survey for immigrant and Australian-born cancer patients: a Rasch analysis.
AB  - PURPOSE: The purpose of this study was to assess the invariance of a culturally
      competent multi-lingual unmet needs survey. METHODS: A cross-sectional study was
      conducted among immigrants of Arabic-, Chinese- and Greek-speaking backgrounds,
      and Anglo-Australian-born controls, recruited through Cancer Registries (n = 591)
      and oncology clinics (n = 900). The survey included four subscales, with newly
      developed items addressing unmet need in culturally competent health information
      and patient support (CCHIPS), and items adapted from existing questionnaires
      addressing physical and daily living (PDL), sexuality (SEX) and survivorship
      (SURV) unmet need. The survey was translated into Arabic, Chinese and Greek.
      Rasch analysis was carried out on the four domains. RESULTS: Whilst many items
      were mistargeted to less prevalent areas of unmet need, causing substantial floor
      effects in person estimates, reliability indices were acceptable. The CCHIPS
      domain showed differential item functioning (DIF) for cultural background and
      language, and the PDL domain showed DIF for treatment phase and gender. The
      results for SEX and SURV domains were limited by floor effects and missing
      responses. All domains showed adequate fit to the model after DIF was resolved
      and a small number of items were deleted. CONCLUSIONS: The study highlights the
      intricacies in designing a culturally competent survey that can be applied to
      culturally and linguistically diverse groups across different treatment contexts.
      Overall, the results demonstrate that this survey is somewhat invariant with
      respect to these factors. Future refinements are suggested to enhance the
      survey's cultural competence and general validity.

PMID- 24859037
TI  - The dengue virus NS2B-NS3 protease retains the closed conformation in the complex
      with BPTI.
AB  - The C-terminal beta-hairpin of NS2B (NS2Bc) in the dengue virus NS2B-NS3 protease
      is required for full enzymatic activity. In crystal structures without inhibitor
      and in the complex with bovine pancreatic trypsin inhibitor (BPTI), NS2Bc is
      displaced from the active site. In contrast, nuclear magnetic resonance (NMR)
      studies in solution only ever showed NS2Bc in the enzymatically active closed
      conformation. Here we demonstrate by pseudocontact shifts from a lanthanide tag
      that NS2Bc remains in the closed conformation also in the complex with BPTI.
      Therefore, the closed conformation is the best template for drug discovery. 

PMID- 24859035
TI  - Pharmacokinetics of antiretrovirals in genital secretions and anatomic sites of
      HIV transmission: implications for HIV prevention.
AB  - The incidence of HIV remains alarmingly high in many parts of the world.
      Prophylactic use of antiretrovirals, capable of concentrating in the anatomical
      sites of transmission, may reduce the risk of infection after an unprotected
      sexual exposure. To date, orally and topically administered antiretrovirals have
      exhibited variable success in preventing HIV transmission in large-scale clinical
      trials. Antiretroviral mucosal pharmacokinetics may help explain the outcomes of
      these investigations. Penetration and accumulation of antiretrovirals into sites
      of transmission can influence dosing strategies and pre-exposure prophylaxis
      clinical trial design. Antiretroviral tissue distribution varies widely within
      and between drug classes, attributed in part to their physicochemical properties
      and tissue-specific drug transporter expression. Nucleoside(-tide) reverse
      transcriptase inhibitors, the CCR5 antagonist maraviroc, and the integrase
      inhibitor raltegravir demonstrate the highest penetration into the male and
      female reproductive tracts and colorectal tissue relative to blood. This review
      describes antiretroviral exposure in anatomic sites of transmission, and places
      these findings in context with the prevention of HIV and the efficacy of pre
      exposure prophylactic strategies. 

PMID- 24859039
TI  - Resonance Raman and FTIR spectroscopic characterization of the closed and open
      states of channelrhodopsin-1.
AB  - Channelrhodopsin-1 from Chlamydomonas augustae (CaChR1) is a light-activated
      cation channel, which is a promising optogenetic tool. We show by resonance Raman
      spectroscopy and retinal extraction followed by high pressure liquid
      chromatography (HPLC) that the isomeric ratio of all-trans to 13-cis of
      solubilized channelrhodopsin-1 is with 70:30 identical to channelrhodopsin-2 from
      Chlamydomonas reinhardtii (CrChR2). Critical frequency shifts in the retinal
      vibrations are identified in the Raman spectrum upon transition to the open
      (conductive P2(380)) state. Fourier transform infrared spectroscopy (FTIR)
      spectra indicate different structures of the open states in the two
      channelrhodopsins as reflected by the amide I bands and the protonation pattern
      of acidic amino acids. 

PMID- 24859038
TI  - Crystal structure of an efficacious gonococcal adherence inhibitor: an enolase
      from Lactobacillus gasseri.
AB  - Enolases are highly conserved metalloenzymes ubiquitous to cellular metabolism.
      While these enzymes share a large degree of sequence and structural similarity,
      they have been shown to possess a wide range of moonlighting functions. Recent
      studies showed that an enolase from Lactobacillus gasseri impedes the ability of
      Neisseria gonorrhoeae to adhere to epithelial cells. We present the crystal
      structure of this enolase, the first from Lactobacillus, with one of its Mg(2+)
      cofactors. Determined using molecular replacement to 2.08A, the structure has a
      flexible and surface exposed catalytic loop containing lysines, and may play a
      role in the inhibitory function. 

PMID- 24859040
TI  - Metallothionein-III increases ADAM10 activity in association with furin, PC7, and
      PKCalpha during non-amyloidogenic processing.
AB  - A-disintegrin and metalloproteinase 10 (ADAM10) is involved in the generation of
      amyloid-beta (Abeta) during amyloid precursor protein (APP) processing, and has a
      protective effect against Abeta neurotoxicity. We explored how metallothionein
      III (MT-III) is regulated in the non-amyloidogenic pathway to generate soluble
      APPalpha (sAPPalpha). MT-III increased sAPPalpha levels and reduced Abeta peptide
      levels, but did not affect ADAM10 expression. However, MT-III increased the
      activity of ADAM10. MT-III-induced sAPPalpha secretion, and Abeta peptide
      formation was blocked by specific inhibitors of furin, proprotein convertase7
      (PC7), and PKCalpha. These results demonstrate that MT-III increases the amount
      of active ADAM10 in association with furin, PC7 and PKCalpha. 

PMID- 24859042
TI  - Race/ethnicity moderates the relationship between depressive symptom severity and
      C-reactive protein: 2005-2010 NHANES data.
AB  - Because few studies have examined depression facets or potential moderators of
      the depression-inflammation relationship, our aims were to determine whether
      particular depressive symptom clusters are more strongly associated with C
      reactive protein (CRP) levels and whether race/ethnicity moderates these
      relationships. We examined data from 10,149 adults representative of the U.S.
      population (4858 non-Hispanic White, 1978 non-Hispanic Black, 2260 Mexican
      American, 1053 Other Hispanic) who participated in the cross-sectional National
      Health and Nutrition Examination Survey between 2005 and 2010. Depressive
      symptoms were assessed by the Patient Health Questionnaire-9, and high
      sensitivity serum CRP was quantified by latex-enhanced nephelometry. Total
      (p<.001), somatic (p<.001), and nonsomatic (p=.001) depressive symptoms were each
      positively related to serum CRP in individual models. However, in the
      simultaneous model that included both symptom clusters, somatic symptoms
      (p<.001), but not nonsomatic symptoms (p=.98), remained associated with serum
      CRP. Evidence of moderation by race/ethnicity was also observed, as six of the
      nine depressive symptoms*race/ethnicity interactions were significant (ps<.05).
      Among non-Hispanic Whites, the pattern of results was identical to the full
      sample; only somatic symptoms (p<.001) remained related to serum CRP in the
      simultaneous model. No relationships between total, somatic, or nonsomatic
      symptoms and serum CRP were observed among the non-Hispanic Black, Mexican
      American, or Other Hispanic groups. Our findings indicate that the link between
      depressive symptoms and systemic inflammation may be due to the somatic symptoms
      of sleep disturbance, fatigue, appetite changes, and psychomotor
      retardation/agitation and may be strongest among non-Hispanic Whites. 

PMID- 24859043
TI  - Single and combined effects of prenatal immune activation and peripubertal stress
      on parvalbumin and reelin expression in the hippocampal formation.
AB  - Exposure to prenatal infection and traumatizing experiences in peripubertal life
      are two environmental risk factors for developmental neuropsychiatric disorders.
      Modeling the cumulative neuronal impact of these factors in a translational
      animal model has led to the recent identification of pathological interactions
      between these environmental adversities in the development of adult brain
      dysfunctions. The present study explored the consequences of combined prenatal
      immune challenge and peripubertal stress on discrete cellular abnormalities in
      the gamma-aminobutyric acid (GABA) system of the hippocampus. Pregnant mice were
      treated with the viral mimetic poly(I:C) (=polyriboinosinic-polyribocytidilic
      acid) or control solution, and offspring born to poly(I:C)-exposed or control
      mothers were then left undisturbed or subjected to unpredictable sub-chronic
      stress during peripubertal development. Stereological estimations of parvalbumin
      expressing cells revealed a significant reduction of these GABAergic interneurons
      in the ventral dentate gyrus of adult offspring exposed to combined immune
      activation and stress. Single exposure to either environmental factor was
      insufficient to cause similar neuropathology. We further found that peripubertal
      stress exerted opposite effects on reelin-immunoreactive cells in the dorsal
      cornu ammonis (CA) region of the hippocampus, with stress increasing and
      decreasing reelin expression in control offspring and prenatally immune
      challenged animals, respectively. The present data suggest that the combination
      of two environmental risk factors, which have each been implicated in the
      etiology of major neuropsychiatric disease, induces significant but restricted
      neuropathological effects on hippocampal GABAergic cell populations known to be
      affected in brain disorders with neurodevelopmental components. 

PMID- 24859041
TI  - Microglial NLRP3 inflammasome activation mediates IL-1beta-related inflammation
      in prefrontal cortex of depressive rats.
AB  - Depression is an inflammatory disorder. Pro-inflammatory cytokine interleukin-1
      beta (IL-1beta) may play a pivotal role in the central nervous system (CNS)
      inflammation of depression. Here, we investigated IL-1beta alteration in serum,
      cerebrospinal fluid (CSF) and prefrontal cortex (PFC) of chronic unpredictable
      mild stress (CUMS)-exposed rats, a well-documented model of depression, and
      further explored the molecular mechanism by which CUMS procedure induced IL-1beta
      related CNS inflammation. We showed that 12-week CUMS procedure remarkably
      increased PFC IL-1beta mRNA and protein levels in depressive-like behavior of
      rats, without significant alteration of serum and CSF IL-1beta levels. We found
      that CUMS procedure significantly caused PFC nuclear factor kappa B (NF-kappaB)
      inflammatory pathway activation in rats. The intriguing finding in this study was
      the induced activation of nucleotide binding and oligomerization domain-like
      receptor family pyrin domain-containing 3 (NLRP3) inflammasome with the increased
      IL-1beta maturation in PFC of CUMS rats, suggesting a new grade of regulatory
      mechanism for IL-1beta-related CNS inflammation. Moreover, microglial activation
      and astrocytic function impairment were observed in PFC of CUMS rats. The
      increased co-location of NLRP3 and ionized calcium binding adaptor molecule 1
      (Iba1) protein expression supported that microglia in glial cells was the primary
      contributor for CUMS-induced PFC NLRP3 inflammasome activation in rats. These
      alterations in CUMS rats were restored by chronic treatment of the antidepressant
      fluoxetine, indicating that fluoxetine-mediated rat PFC IL-1beta reduction
      involves both transcriptional and post-transcriptional regulatory mechanisms.
      These findings provide in vivo evidence that microglial NLRP3 inflammasome
      activation is a mediator of IL-1beta-related CNS inflammation during chronic
      stress, and suggest a new therapeutic target for the prevention and treatment of
      depression.

PMID- 24859044
TI  - Introduction to immunology at The University of Iowa.

PMID- 24859045
TI  - Species-specific bioaccumulation of halogenated organic pollutants and their
      metabolites in fish serum from an e-waste site, South China.
AB  - Halogenated organic pollutants (HOPs)-including organochlorine pesticides (OCPs),
      polychlorinated biphenyls (PCBs), polybrominated diphenylethers (PBDEs),
      polybromobiphenyls (PBBs), dechlorane plus (DP), tetrabromobisphenol A (TBBPA),
      and hexabromocyclododecanes (HBCDs) as well as PCB metabolites (methylsulfone
      [MeSO2-]) and hydroxylated (OH-) PCBs and OH-PBDEs-were determined in the serum
      of mud carp and northern snakehead from an electronic-waste (e-waste) site in
      South China. The average concentrations (mean +/- SD) of SigmaPCBs, SigmaPBDEs,
      SigmaOCPs, SigmaPBBs, SigmaTBBPA, SigmaHBCDs, and SigmaDP were 1410 +/- 324, 70
      +/- 20, 3.0 +/- 0.4, 2.8 +/- 0.8, 1.6 +/- 0.4, 1.0 +/- 0.2, and 0.3 +/- 0.03 ng/g
      wet weight (ww) in mud carp and 6430 +/- 781, 468 +/- 49, 22.4 +/- 1.1, 7.0 +/-
      0.6, 2.9 +/- 2.3, 5.5 +/- 1.1, and 4.6 +/- 0.6 ng/g ww in northern snakehead,
      respectively. MeSO2-PCBs, OH-PCBs, and OH-PBDEs were detected at a total
      concentration of 0.44 +/- 0.03 and 9.7 +/- 0.3 ng/g ww in mud carp and northern
      snakehead, respectively. The congener profiles of PCBs, PBDEs, OH/MeSO2-PCBs, and
      OH-PBDEs were found to be significantly different between the two fish species,
      possibly as a result of species-specific bioaccumulation and/or metabolism of the
      HOPs. Chirality of ten PCB congeners and alpha-HBCD, as well as the f anti values
      of DP in the serum samples, supported the species-specific biotransformation of
      HOPs. Furthermore, the presence of covaried and counter-varied enantiomeric
      fractions of PCBs between the two fish species indicated species- and congener
      specific enantiomer enrichment of PCBs. 

PMID- 24859046
TI  - Urinary perchlorate exposure and risk in women of reproductive age in a fireworks
      production area of China.
AB  - Perchlorate is used widely in fireworks, and, if ingested, it has the potential
      to disrupt thyroid function. The concentrations of perchlorate in water and soil
      samples and in urine samples of women of reproductive age from Liuyang, the
      largest fireworks production area in China, were investigated. The results showed
      that the average perchlorate concentrations in groundwater, surface water,
      farmland soil, and urine samples of women from the fireworks production area were
      significantly greater than those from the control area. The health risk of
      perchlorate ingested through drinking water was assessed based on the mode
      recommended by the United States Environmental Protection Agency. The values of
      hazard quotient of river water and groundwater in the fireworks production area
      were much greater than the safe level (=1), which indicates that adverse health
      effects may result from perchlorate when these sources of water are used as
      drinking water. These results indicated that the environment of the fireworks
      production area has been polluted by perchlorate and that residents were and are
      facing greater exposure doses of perchlorate. Fireworks production enterprises
      may be a major source of perchlorate contamination. 

PMID- 24859047
TI  - Are children with autism more responsive to animated characters? A study of
      interactions with humans and human-controlled avatars.
AB  - Few direct comparisons have been made between the responsiveness of children with
      autism to computer-generated or animated characters and their responsiveness to
      humans. Twelve 4- to 8-year-old children with autism interacted with a human
      therapist; a human-controlled, interactive avatar in a theme park; a human actor
      speaking like the avatar; and cartoon characters who sought social responses. We
      found superior gestural and verbal responses to the therapist; intermediate
      response levels to the avatar and the actor; and poorest responses to the cartoon
      characters, although attention was equivalent across conditions. These results
      suggest that even avatars that provide live, responsive interactions are not
      superior to human therapists in eliciting verbal and non-verbal communication
      from children with autism in this age range. 

PMID- 24859048
TI  - Construction of high-quality Caco-2 three-frame cDNA library and its application
      to yeast two-hybrid for the human astrovirus protein-protein interaction.
AB  - Human epithelial colorectal adenocarcinoma (Caco-2) cells are widely used as an
      in vitro model of the human small intestinal mucosa. Caco-2 cells are host cells
      of the human astrovirus (HAstV) and other enteroviruses. High quality cDNA
      libraries are pertinent resources and critical tools for protein-protein
      interaction research, but are currently unavailable for Caco-2 cells. To
      construct a three-open reading frame, full length-expression cDNA library from
      the Caco-2 cell line for application to HAstV protein-protein interaction
      screening, total RNA was extracted from Caco-2 cells. The switching mechanism at
      the 5' end of the RNA transcript technique was used for cDNA synthesis. Double
      stranded cDNA was digested by Sfi I and ligated to reconstruct a pGADT7-Sfi I
      three-frame vector. The ligation mixture was transformed into Escherichia coli
      HST08 premium electro cells by electroporation to construct the primary cDNA
      library. The library capacity was 1.0*10(6)clones. Gel electrophoresis results
      indicated that the fragments ranged from 0.5kb to 4.2kb. Randomly picked clones
      show that the recombination rate was 100%. The three-frame primary cDNA library
      plasmid mixture (5*10(5)cfu) was also transformed into E. coli HST08 premium
      electro cells, and all clones were harvested to amplify the cDNA library. To
      detect the sufficiency of the cDNA library, HAstV capsid protein as bait was
      screened and tested against the Caco-2 cDNA library by a yeast two-hybrid (Y2H)
      system. A total of 20 proteins were found to interact with the capsid protein.
      These results showed that a high-quality three-frame cDNA library from Caco-2
      cells was successfully constructed. This library was efficient for the
      application to the Y2H system, and could be used for future research.

PMID- 24859049
TI  - A virus-envelope paired competitive assay to study entry efficiency of human
      immunodeficiency virus type 1 in vitro.
AB  - The efficiency of the human immunodeficiency virus type-1 (HIV-1) to enter cells
      is defined primarily by amino acid exchanges in the external glycoprotein gp120
      and in, especially its highly variable V3 loop region. To study entry efficiency
      of HIV-1 a competitive viral entry assay was developed, to be comprised of
      infectious virus as well as soluble gp120 (sgp120) as an entry competitor. Entry
      of viruses using the coreceptor CXCR4 was reduced by adding CXCR4-tropic sgp120
      (X4-sgp120) SF2 or LAV expressed in the baculovirus system or by adding X4-sgp120
      from NL-952 and NL-V3A virus mutants produced in a HeLa-P4 cell culture
      expression system. Adding X4-sgp120 into a CCR5-specific infection assay revealed
      that X4-sgp120 enhanced the infection of CCR5-tropic virus. Furthermore, the role
      of the V3 loop N-glycan g15 on entry efficiency was studied using virus mutants
      and sgp120 with different N-glycosylation and different coreceptor usage. These
      experiments showed that viral entry of R5-tropic viruses lacking the N-glycan g15
      within the V3 loop was inhibited by CCR5-tropic sgp120 harboring the g15 N
      glycan. Altogether, the data demonstrate that HIV-1 entry efficiency can be
      studied easily by using sgp120 as an internal control or by using autologous or
      heterologous sgp120-virus pairs.

PMID- 24859050
TI  - A duplex recombinant viral nucleoprotein microbead immunoassay for simultaneous
      detection of seroresponses to human respiratory syncytial virus and
      metapneumovirus infections.
AB  - Serologic diagnosis of human respiratory syncytial virus (hRSV) and human
      metapneumovirus (hMPV) infections has been shown to complement virus detection
      methods in epidemiologic studies. Enzyme immunoassays (EIAs) using cultured virus
      lysate antigens are often used to diagnose infection by demonstration of a >=4
      fold rises in antibody titer between acute and convalescent serum pairs. In this
      study, hRSV and hMPV nucleocapsid (recN) proteins were expressed in a baculovirus
      system and their performance compared with virus culture lysate antigen in EIAs
      using paired serum specimens collected from symptomatic children. The recN
      proteins were also used to develop a duplex assay based on the Luminex microbead
      based suspension array technology, where diagnostic rises in antibody levels
      could be determined simultaneously at a single serum dilution. Antibody levels
      measured by the recN and viral lysate EIAs correlated moderately (hRSV,
      r(2)=0.72; hMPV, r(2)=0.76); the recN EIAs identified correctly 35 of 37 (94.6%)
      and 48 of 50 (96%) serum pairs showing diagnostic antibody rises by viral lysate
      EIAs. Purified recN proteins were then coupled to microbeads and serum pairs were
      tested at a single dilution on a Luminex MAGPIX((r)) analyzer. The duplex recN
      assay identified correctly 33 of 39 (85%) and 41 of 47 (86.7%) serum pairs
      showing diagnostic rises to hRSV and hMPV, respectively. The recN assay permits
      simultaneous testing for acute hRSV and hMPV infections and offers a platform for
      expanded multiplexing of other respiratory virus assays. 

PMID- 24859051
TI  - Cationic vesicles based on non-ionic surfactant and synthetic aminolipids mediate
      delivery of antisense oligonucleotides into mammalian cells.
AB  - A formulation based on a synthetic aminolipid containing a double-tailed with two
      saturated alkyl chains along with a non-ionic surfactant polysorbate-80 has been
      used to form lipoplexes with an antisense oligonucleotide capable of inhibiting
      the expression of Renilla luciferase mRNA. The resultant lipoplexes were
      characterized in terms of morphology, Zeta potential, average size, stability and
      electrophoretic shift assay. The lipoplexes did not show any cytotoxicity in cell
      culture up to 150 mM concentration. The gene inhibition studies demonstrated that
      synthetic cationic vesicles based on non-ionic surfactant and the appropriate
      aminolipid play an important role in enhancing cellular uptake of antisense
      oligonucleotides obtaining promising results and efficiencies comparable to
      commercially available cationic lipids in cultured mammalian cells. Based on
      these results, this amino lipid moiety could be considered as starting point for
      the synthesis of novel cationic lipids to obtain potential non-viral carriers for
      antisense and RNA interference therapies.

PMID- 24859052
TI  - ATR-FTIR spectroscopic evidence for biomolecular phosphorus and carboxyl groups
      facilitating bacterial adhesion to iron oxides.
AB  - Attenuated total reflectance (ATR) Fourier transform infrared (FTIR) spectroscopy
      has been used to probe the binding of bacteria to hematite (alpha-Fe2O3) and
      goethite (alpha-FeOOH). In situ ATR-FTIR experiments with bacteria (Pseudomonas
      putida, Pseudomonas aeruginosa, Escherichia coli), mixed amino acids, polypeptide
      extracts, deoxyribonucleic acid (DNA), and a suite of model compounds were
      conducted. These compounds represent carboxyl, catecholate, amide, and phosphate
      groups present in siderophores, amino acids, polysaccharides, phospholipids, and
      DNA. Due in part to the ubiquitous presence of carboxyl groups in biomolecules,
      numerous IR peaks corresponding to outer-sphere or unbound (1400 cm(-1)) and
      inner-sphere (1310-1320 cm(-1)) coordinated carboxyl groups are noted following
      reaction of bacteria and biomolecules with alpha-Fe2O3 and alpha-FeOOH. However,
      the data also reveal that the presence of low-level amounts (i.e., 0.45-0.79%) of
      biomolecular phosphorous groups result in strong IR bands at ~1043 cm(-1),
      corresponding to inner-sphere Fe-O-P bonds, underscoring the importance of
      bacteria associated P-containing groups in biomolecule and cell adhesion.
      Spectral comparisons also reveal slightly greater P-O-Fe contributions for
      bacteria (Pseudomonad, E. coli) deposited on alpha-FeOOH, as compared to alpha
      Fe2O3. This data demonstrates that slight differences in bacterial adhesion to Fe
      oxides can be attributed to bacterial species and Fe-oxide minerals. However,
      more importantly, the strong binding affinity of phosphate in all bacteria
      samples to both Fe-oxides results in the formation of inner-sphere Fe-O-P bonds,
      signifying the critical role of biomolecular P in the initiation of bacterial
      adhesion.

PMID- 24859053
TI  - Longitudinal assessment of bone quality in pediatric patients with chronic kidney
      disease in relation to treatment modality.
AB  - Children with chronic kidney disease (CKD) are at high risk of developing
      impaired bone quality. Our aim was to investigate changes of bone quality in
      children with CKD in relation to their treatmant using two imaging techniques
      dual energy X-ray absorptiometry and quantitative ultraSonography (QUS). Thirty
      three patients with CKD (18 boys and 15 girls, mean age 10.37 +/- 3.37 years)
      were evaluated with bone mineral density (BMD) measured by DXA at the lumbar
      spine and hip and with speed of sound (SOS) measured by QUS at the radius and
      tibia at the beginning and at the end of the study. The patient cohort consisted
      of 14 patients with CKD stage 3-4 not treated with dialysis (CKD group), 5
      patients on peritoneal dialysis treatment (PD group) and 14 patients after kidney
      transplantation (RTx group). BMD measurements did not show any significant
      changes in CKD and PD patients during the study. There was a reduction in BMD
      measured at the lumbar spine, femoral neck and total hip in RTx patients that was
      approaching significance. During the 2-year follow-up, SOS measurements at the
      radius decreased significantly in PD patients, whereas SOS measurements at the
      tibia significantly improved in RTx patients. No significant changes in QUS
      parameters were recorded for patients in the CKD group. In conclusion, our study
      shows that QUS parameters seem to better reflect the state of hyperparathyroidism
      of renal osteodystrophy as they deteriorate significantly in patients on dialysis
      and improve after renal transplantation.

PMID- 24859054
TI  - Hairy Root Induction in Helicteres isora L. and Production of Diosgenin in Hairy
      Roots.
AB  - Mature seeds of Helicteres isora L. were collected from seven geographical
      locations of Maharashtra and Goa (India) and evaluated for diosgenin (a bioactive
      steroidal sapogenin of prime importance) extraction and quantification.
      Chemotypic variations were evidenced with diosgenin quantity ranging from 33 MUg
      g(-1) seeds (Osmanabad forests) to 138 MUg g(-1) (Khopoli region). Nodal and leaf
      explants from in vitro-raised seedlings were used for callus and Agrobacterium
      mediated transformation, respectively. Compact, hard, whitish-green callus (2.65
      g explant(-1)) was obtained on MS + 13.32 MUM BAP + 2.32 MUM Kin after 30 days of
      inoculation. Various parameters including types of explant and Agrobacterium
      strain, culture density, duration of infection and various medium compositions
      were optimized for hairy root production. A. rhizogenes strain ATCC-15834
      successfully induced hairy roots from leaf explants (1 cm(2)) with 42 %
      efficiency. Transgenic status of the roots was confirmed by PCR using rolB and
      VirD specific primers. Hairy roots showed an ability to synthesize diosgenin.
      Diosgenin yield was increased ~8 times in hairy roots and ~5 times in callus than
      the seeds of wild plants. Enhanced diosgenin content was associated with proline
      accumulation in hairy roots. This is the first report on induction of hairy roots
      in H. isora. 

PMID- 24859055
TI  - Isolation and genomic sequence of hepatitis A virus from mixed frozen berries in
      Italy.
AB  - Hepatitis A virus (HAV) was detected in two samples of mixed frozen berries
      linked to Italian hepatitis A outbreak in April and September 2013. Both viruses
      were fully sequenced by next-generation sequencing and the genomes clustered with
      HAV complete genomes of sub-genotype IA with nucleotide identities of 95-97%.

PMID- 24859056
TI  - Enhanced dendritic cell maturation by the B-chain of Korean mistletoe lectin (KML
      B), a novel TLR4 agonist.
AB  - Korean mistletoe lectin (KML) is composed of A and B sub-chains. The B-chain
      binds to cell surfaces, whereas the A-chain hinders translation because it is a
      RIP (ribosome inactivating protein) inducing apoptosis. Although KML has various
      biological and immunological activities, its potential use in cancer therapy or
      as an adjuvant therapy is limited by its toxicity to normal cells. This study was
      conducted to determine whether the B-chain of KML (KML-B) has immunoadjuvant
      activity and cytotoxicity activity. To evaluate the immunomodulatory activities
      of B chain KML, in vitro experiments employing bone marrow-derived dendritic
      cells (BMDCs) were performed. Dendritic cells (DCs) are a unique group of white
      blood cells that are able to capture and process antigens for presentation to T
      cells, which constitute primary immune response. In the present study, KML-B was
      found to be non-cytotoxic to BMDCs. Furthermore, the expressions of co
      stimulatory molecules (CD40, CD80, CD86, and MHC II) and the secretions of
      cytokines (IL-1beta, IL-6, IL-12p70, and TNF-alpha) were increased in BMDCs by
      KML-B. In addition, other indicators (antigen-uptake and CCR7 expression) of BMDC
      maturation were changed by KML-B, and the ability of KML-B to enhance various
      functions by BMDCs was found to be dependent on TLR4 expression. Moreover, BMDCs
      matured by KML-B induced naive CD4(+) T cell differentiation toward Th1 cells
      directly and indirectly. These experiments confirm that KML-B exhibits potent
      immunomodulatory properties and suggest that KML-B be considered a potential
      dendritic cell-based cancer therapy and immunoadjuvant. 

PMID- 24859057
TI  - Treatment with the C5a receptor/CD88 antagonist PMX205 reduces inflammation in a
      murine model of allergic asthma.
AB  - Allergic asthma is a chronic inflammatory airway disease arising from an aberrant
      immune response following exposure to environmental stimuli in genetically
      susceptible persons. The complement component 5 (C5)/C5a Receptor (C5aR/CD88)
      signaling pathway has been implicated in both experimental allergic asthma and
      human asthmatic disease. Targeting the C5a/C5aR signaling pathway in rodent
      models has been shown to either enhance or reduce allergic asthma consequences.
      Treatment with a recombinant humanized monoclonal antibody directed against C5
      has shown unclear results in patients with asthma. The objective of this proof-of
      concept animal study was to determine whether the low molecular weight C5aR
      peptidomimetic antagonist, PMX205, would reduce experimental allergic asthma
      consequences in mice. PMX205 or vehicle control was administered subcutaneously
      to BALB/c mice prior to and during standard ovalbumin (OVA) allergen
      sensitization and aerosolized challenge phases. PMX205 substantially reduced OVA
      induced total cell (60%), neutrophil (66%) and eosinophil (65%) influxes in
      lavage fluid sampling. There were also significant reductions in OVA-induced
      lavage fluid IL-13 protein and lung Th2 cytokine gene expression with PMX205
      administration. PMX205 treatment also diminished OVA-induced lung parenchyma
      cellular infiltration. PMX205 administration did not reduce OVA-induced serum IgE
      levels or epithelial mucous/goblet cell generation. There was no evidence of
      toxicity observed with PMX205 treatment in saline or OVA-challenged animals.
      These data provide evidence that pharmacologic blockade of C5aR by a low
      molecular weight antagonist (PMX205) reduces airway inflammatory cell and
      cytokine responses in experimental allergic asthma, and suggests that PMX205
      might represent a novel therapeutic agent for reducing asthmatic outcomes. 

PMID- 24859058
TI  - Baicalein ameliorates inflammatory-related apoptotic and catabolic phenotypes in
      human chondrocytes.
AB  - Osteoarthritis (OA), characterized by progressive destruction of articular
      cartilage, is the most common form of human arthritis and a major concern for
      aging societies worldwide. In OA, pro-inflammatory cytokines such as interleukin
      (IL)-1beta and tumor necrosis factor (TNF)-alpha can trigger the caspase cascade
      to promote apoptosis and activate NF-kappaB to induce catabolic factors in
      chondrocytes. Here, the anti-apoptotic and anti-catabolic effects of baicalein on
      human OA chondrocytes treated by a mixture of IL-1beta and TNF-alpha (IT) were
      investigated in vitro. In cultured chondrocytes, baicalein pretreatment
      attenuated apoptosis in a concentration-dependent manner in response to IT
      stimulation. Mechanistically, the anti-apoptotic effects of baicalein result from
      inhibition of nitric oxide production and downstream caspase signaling pathway.
      Moreover, administration of baicalein significantly reduced matrix
      metalloproteinase (MMP) 3 and MMP13 secretion in chondrocytes stimulated with IT.
      The anti-catabolic effects of baicalein were further demonstrated by the recovery
      of the glycosaminoglycan and type II collagen (COLII) deposition by histological
      analysis in IT-treated mouse articular cartilage explants. These findings suggest
      that baicalein might be a promising novel therapeutic agent for OA by virtue of
      its suppression of apoptosis and MMP secretion in OA chondrocytes. 

PMID- 24859059
TI  - In vitro anti-proliferative and anti-angiogenic activities of thalidomide
      dithiocarbamate analogs.
AB  - Inhibition of angiogenesis is currently perceived as a promising strategy in the
      treatment of cancer. The anti-angiogenicity of thalidomide has inspired a second
      wave of research on this teratogenic drug. The present study aimed to investigate
      the anti-proliferative and anti-angiogenic activities of two thalidomide
      dithiocarbamate analogs by studying their anti-proliferative effects on human
      umbilical vein endothelial cells (HUVECs) and MDA-MB-231 human breast cancer cell
      lines. Their action on the expression levels of IL-6, IL-8, TNF-alpha, VEGF165,
      and MMP-2 was also assessed. Furthermore, their effect on angiogenesis was
      evaluated through wound healing, migration, tube formation, and nitric oxide (NO)
      assays. Results illustrated that the proliferation of HUVECs and MDA-MB-231 cells
      was not significantly affected by thalidomide at 6.25-100MUM. Thalidomide failed
      to block angiogenesis at similar concentrations. By contrast, thalidomide
      dithiocarbamate analogs exhibited significant anti-proliferative action on HUVECs
      and MDA-MB-231 cells without causing cytotoxicity and also showed powerful anti
      angiogenicity in wound healing, migration, tube formation, and NO assays.
      Thalidomide analogs 1 and 2 demonstrated more potent activity to suppress
      expression levels of IL-6, IL-8, TNF-alpha, VEGF165, and MMP-2 than thalidomide.
      Analog 1 consistently, showed the highest potency and efficacy in all the assays.
      Taken together, our results support further development and evaluation of novel
      thalidomide analogs as anti-tumor and anti-angiogenic agents. 

PMID- 24859060
TI  - Specific binding of intravenous immunoglobulin products to tau peptide fragments.
AB  - The effects of intravenous immunoglobulin (IVIG) products are being evaluated in
      Alzheimer's disease (AD) patients. IVIG contains antibodies to tau protein, the
      main constituent of neurofibrillary tangles (NFTs). Tau has microtubule binding
      domain (MBD) repeats which are thought to be necessary for its aggregation, a key
      process in NFT formation. Tau's N-terminal region may also contribute to its
      aggregation and to the neurotoxicity of its soluble oligomers. This study
      examined the specific binding of IVIG products Gammagard, Gamunex, and Flebogamma
      to a tau N-terminal fragment (tau 45-73), tau's four MBD repeat sequences (tau
      244-274, 275-305, 306-336, and 337-368), and a tau C-terminal fragment (tau 422
      441). Mean antibody levels to tau 45-73 and tau 422-441 were significantly higher
      in Gamunex than in Gammagard and Flebogamma, while there were no significant
      differences between IVIG products for antibody concentrations to the MBD repeat
      sequences. Patterns of binding to tau fragments differed between IVIG products.
      Gammagard's highest binding was to tau 275-305 and tau 306-336 while Gamunex
      bound preferentially to tau 45-73 and tau 422-441. Flebogamma's binding to tau
      275-305 and tau 306-336 was greater than to tau 337-368, and its binding to tau
      306-336 was also higher than to tau 422-441. These findings indicate that IVIG
      products vary with respect to their binding to different regions of tau. This
      could result in differences with regard to their ability to prevent tau's
      aggregation and/or tau soluble oligomer neurotoxicity. 

PMID- 24859062
TI  - Salmonella Typhi shdA: pseudogene or allelic variant?
AB  - ShdA from Salmonella Typhimurium (ShdASTm) is a large outer membrane protein that
      specifically recognizes and binds to fibronectin. ShdASTm is involved in the
      colonization of the cecum and the Peyer's patches of terminal ileum in mice. On
      the other hand, shdA gene from Salmonella Typhi (shdASTy) has been considered a
      pseudogene (i.e. a nonfunctional sequence of genomic DNA) due to the presence of
      deletions and mutations that gave rise to premature stop codons. In this work we
      show that, despite the deletions and mutations, shdASTy is fully functional. S.
      Typhi DeltashdA mutants presented an impaired adherence and invasion of HEp-2 pre
      treated with TGF-beta1, an inducer of fibronectin production. Moreover, shdA from
      S. Typhi and S. Typhimurium seem to be equivalent since shdASTm restored the
      adherence and invasion of S. Typhi DeltashdA mutant to wild type levels. In
      addition, anti-FLAG mAbs interfered with the adherence and invasion of the S.
      Typhi shdA-3xFLAG strain. Finally, shdASTy encodes a detectable protein when
      heterologously expressed in Escherichia coli DH5alpha. The data presented here
      show that shdASTy is not a pseudogene, but a different functional allele compared
      with shdASTm. 

PMID- 24859061
TI  - Therapeutic potential of chloroquine in a murine model of inflammatory bowel
      disease.
AB  - Inflammatory bowel disease (IBD) is an idiopathic chronic inflammation of the
      gastrointestinal tract which is mainly caused by dysregulated gut immune response
      to commensal flora. Very limited treatment options with marginal efficacy are
      available along with surgery which has high risk of reoccurrence. As both innate
      and adaptive immune responses have been found altered in IBD, a good therapeutic
      strategy could be to restrict both of them under chronic inflammatory conditions.
      Effect of chloroquine on TLR9 signaling is well reported, while there are limited
      studies on non-endosomal TLRs as well as T cell responses. Hence, we studied its
      effect on other TLRs as well as T cell response along with testing it as a
      potential therapeutics in IBD using murine preclinical colitis model. Chloroquine
      significantly suppressed the TLR2 as well as TLR9 signaling in both in vitro as
      well as in vivo experimental settings, while it had no effect on TLR4 pathway. It
      also suppressed the T cell cytokine and proliferative responses. In, DSS-induced
      murine colitis model, chloroquine administration, significantly improved body
      weight loss, colon length shortening, tissue damage and inflammatory cell
      infiltration. Based on our findings in preclinical murine model of IBD,
      chloroquine has the potential to be considered as a therapeutic option in clinics
      through inhibition of diverse TLR and T cell responses. 

PMID- 24859064
TI  - Heart perforation by pro-MRI right ventricular lead in a 26-year-old woman.

PMID- 24859063
TI  - Cryoballoon ablation of paroxysmal atrial fibrillation and underlying atrial
      tachycardia and ectopy arising from a common trigger focus limited to a right
      inferior pulmonary vein.

PMID- 24859065
TI  - Acute coronary syndrome and single coronary artery ostium.

PMID- 24859066
TI  - Ventricular fibrillation in a marathon mountain bike racer.

PMID- 24859067
TI  - [Acute myocarditis complicated by pulmonary embolism].

PMID- 24859068
TI  - One patient: double massive pulmonary embolism with haemodynamic collapse managed
      by emergent surgery.

PMID- 24859069
TI  - Pitfalls of fractional flow reserve.

PMID- 24859070
TI  - Transient dynamic left ventricular outflow tract obstruction in a patient with
      pheochromocytoma.

PMID- 24859071
TI  - Dynamic ECG changes in a patient with subarachnoid haemorrhage.

PMID- 24859072
TI  - Authors' response.

PMID- 24859073
TI  - MGuardTM stent... We beg to differ. Commentary to the article "Long-term follow
      up of mesh-covered stent implantation in patients with ST-segment elevation
      myocardial infarction".

PMID- 24859074
TI  - Risk Assessment of residual monomer migrating from acrylic polymers and causing
      Allergic Contact Dermatitis during normal handling and use.
AB  - Acrylic, Poly Methyl Methacrylate (PMMA) based polymers are found in many
      industrial, professional and consumer products and are of low toxicity, but do
      contain very low levels of residual monomers and process chemicals that can leach
      out during handling and use. Methyl Methacrylate, the principle monomer is of low
      toxicity, but is a recognized weak skin sensitizer. The risk of induction of
      contact allergy in consumers was determined using a method based upon the
      Exposure-based Quantitative Risk Assessment approach developed for fragrance
      ingredients. The No Expected Sensitization Induction Level (NESIL) was based on
      the threshold to induction of sensitization (EC3) in the Local Lymph Node Assay
      (LLNA) since no Human Repeat Insult Patch Test (HRIPT) data were available.
      Categorical estimation of Consumer Exposure Level was substituted with a worst
      case assumption based upon the quantitative determination of MMA monomer
      migration into simulants. Application of default and Chemical-Specific Adjustment
      Factors results in a Risk Characterization Ratio (RCR) of 10,000 and a high
      Margin of Safety for induction of Allergic Contact Dermatitis (ACD) in consumers
      handling polymers under conservative exposure conditions. Although there are no
      data available to derive a RCR for elicitation of ACD it is likely to be lower
      than that for induction. 

PMID- 24859075
TI  - Cannabis, pesticides and conflicting laws: the dilemma for legalized States and
      implications for public health.
AB  - State laws on the legalization of medical and recreational cannabis are rapidly
      evolving. Similar to other crops, cannabis is susceptible to multiple pests
      during cultivation. Growers have an economic incentive to produce large yields
      and high quality plants, and may resort to pesticides to achieve these outcomes.
      Currently, there are no pesticides registered for cannabis in the United States,
      given its illegal status by the federal government. This discrepancy creates a
      regulatory vacuum and dilemma for States with legal medical and recreational
      cannabis that seek to balance lawful compliance with pesticides and worker or
      public health. Pesticide use presents occupational safety issues that can be
      mitigated through established worker protection measures. The absence of approved
      products for cannabis may result in consumer exposures to otherwise more
      hazardous pesticides or higher residue levels. While many legal and scientific
      hurdles exist to register conventional pesticides for use on cannabis, legalized
      States have explored other opportunities to leverage the present regulatory
      infrastructure. Stakeholder engagement and outreach to the cannabis industry from
      credible sources could mitigate pesticide misuse and harm. 

PMID- 24859076
TI  - Perceived independence and limitations in rising and sitting down after
      rehabilitation for a lower-limb amputation.
AB  - OBJECTIVE: To study perceived independence in rising and perceived limitations in
      rising and sitting down in persons after a lower-limb amputation and the
      relationship of these perceptions with personal and clinical characteristics.
      DESIGN: Cross-sectional study. SUBJECTS/PATIENTS: Persons with a lower-limb
      amputation wearing a prosthesis (n = 172). METHODS: Perceived independence in
      rising was assessed with the Locomotor Capabilities Index. Limitations in rising
      and sitting down were assessed with the Questionnaire Rising and Sitting down.
      Multivariate logistic and linear regression analyses, respectively, were used to
      investigate the associations between independence and limitations in rising and
      sitting down, and personal and clinical characteristics. RESULTS: Of the
      participants, 91% and 47% perceived independence in rising from a chair and
      rising from the floor, respectively. Older participants and women perceived less
      independence in rising. Participants perceived marked limitations in rising and
      sitting down, with those rehabilitated in a nursing home perceiving more
      limitations. CONCLUSION: After a lower-limb amputation, most persons wearing a
      prosthesis are able to rise independently from a chair, but many perceive
      decreased independence in other forms of rising, especially older participants
      and women. Participants, especially those rehabilitated in a nursing home,
      perceive considerable limitations in rising and sitting down. However, in those
      patients rehabilitated in a nursing home these limitations may be due to
      indication bias.

PMID- 24859078
TI  - A System for Anesthesia Drug Administration Using Barcode Technology: The
      Codonics Safe Label System and Smart Anesthesia Manager.
AB  - BACKGROUND: Many anesthetic drug errors result from vial or syringe swaps.
      Scanning the barcodes on vials before drug preparation, creating syringe labels
      that include barcodes, and scanning the syringe label barcodes before drug
      administration may help to prevent errors. In contrast, making syringe labels by
      hand that comply with the recommendations of regulatory agencies and standards
      setting bodies is tedious and time consuming. A computerized system that uses
      vial barcodes and generates barcoded syringe labels could address both safety
      issues and labeling recommendations. METHODS: We measured compliance of syringe
      labels in multiple operating rooms (ORs) with the recommendations of regulatory
      agencies and standards-setting bodies before and after the introduction of the
      Codonics Safe Label System (SLS). The Codonics SLS was then combined with Smart
      Anesthesia Manager software to create an anesthesia barcode drug administration
      system, which allowed us to measure the rate of scanning syringe label barcodes
      at the time of drug administration in 2 cardiothoracic ORs before and after
      introducing a coffee card incentive. Twelve attending cardiothoracic
      anesthesiologists and the OR satellite pharmacy participated. RESULTS: The use of
      the Codonics SLS drug labeling system resulted in >75% compliant syringe labels
      (95% confidence interval, 75%-98%). All syringe labels made using the Codonics
      SLS system were compliant. The average rate of scanning barcodes on syringe
      labels using Smart Anesthesia Manager was 25% (730 of 2976) over 13 weeks but
      increased to 58% (956 of 1645) over 8 weeks after introduction of a simple
      (coffee card) incentive (P < 0.001). CONCLUSIONS: An anesthesia barcode drug
      administration system resulted in a moderate rate of scanning syringe label
      barcodes at the time of drug administration. Further, adaptation of the system
      will be required to achieve a higher utilization rate.

PMID- 24859077
TI  - Length of red cell unit storage and risk for delirium after cardiac surgery.
AB  - BACKGROUND: The time that red cell units are stored before transfusion may be
      associated with postoperative complications, although the evidence is
      conflicting. However, the association between the length of red cell unit storage
      and postoperative delirium has not been explored. We hypothesized that the length
      of storage of transfused red cell units would be associated with delirium after
      cardiac surgery. METHODS: We conducted a case-control study in which patients
      undergoing coronary artery bypass, valve, or ascending aorta surgery with
      cardiopulmonary bypass at Johns Hopkins from 2005 to 2011 were eligible for
      inclusion. Patients were excluded if they did not receive red cell units,
      received >4 red cell units during hospitalization, received any transfusion after
      the first postoperative day, or received red cell units that were not exclusively
      stored for <=14 days or >14 days. Eighty-seven patients met transfusion-related
      inclusion criteria and developed postoperative delirium. Controls who did not
      develop delirium were selected from the same source population of eligible
      patients and were matched 1:1 based on age (+/- 5 years), 2- to 2.5-year band of
      date of surgery, and surgical procedure. For each patient, we calculated the
      average storage duration of all transfused red cell units. The primary outcome
      was odds of delirium in patients who were transfused red cell units with
      exclusive storage duration >14 days compared with that of <=14 days. Secondary
      outcomes were odds of delirium with each increasing day of average red cell unit
      storage duration. We used conditional multivariable regression to test our
      hypotheses. RESULTS: In conditional multivariable analysis of 87 case-control
      pairs, there was no difference in the odds of patients developing delirium if
      they were transfused red cell units with an exclusive storage age >14 days
      compared with that <=14 days (odds ratio [OR] 1.83; 95% confidence interval, 0.73
      4.58, P = 0.20). Each additional day of average red cell unit storage beyond 14
      days was associated with a 1.01- to 1.13-fold increase in the odds of
      postoperative delirium (OR, 1.07; P = 0.03). Each additional day of average
      storage beyond 21 days was associated with a 1.02- to 1.23-fold increase in the
      odds of postoperative delirium (OR, 1.12; P = 0.02). CONCLUSIONS: Transfusion of
      red cell units that have been stored for >14 days is not associated with
      increased odds of delirium. However, each additional day of storage >14 or 21
      days may be associated with increased odds of postoperative delirium in patients
      undergoing cardiac surgery. More research is needed to further characterize the
      association between delirium and storage duration of transfused red cell units.

PMID- 24859079
TI  - The safety of nurse-administered procedural sedation compared to anesthesia care
      in a historical cohort of advanced endoscopy patients.
AB  - BACKGROUND: In April 2010, in response to a change in Centers for Medicare and
      Medicaid Services regulation placing deep sedation under hospital anesthesia
      services, our institution began providing anesthesia care for all advanced
      endoscopic procedures. Because it remains unknown whether anesthesia care reduces
      sedation-related complications or improves quality of care versus nurse
      administered sedation for endoscopic retrograde cholangiopancreatography and
      endoscopic ultrasound patients, we retrospectively compared complications in a 5
      year historical cohort before and after the policy change. METHODS: We reviewed a
      historical cohort of 9598 consecutive endoscopic retrograde
      cholangiopancreatography and endoscopic ultrasound examinations for adult
      patients at a single institution during a 5-year period (October 2007-October
      2012). We compared procedures performed before and after the policy change for
      the incidence of sedation, endoscopic, and total complications, and for major
      morbidity and mortality. RESULTS: The incidence of reported sedation-related
      complications was 0.38% (17 of 4514) before the policy change and 0.08% (4 of
      5084) after the policy change, which was statistically significant (P = 0.002,
      diff = 0.3, 95% confidence interval, 0.11%-0.53%). Endoscopic complications were
      not significantly different before versus after: 0.66% vs 0.87% (P = 0.293, diff
      = 0.2, 95% confidence interval, -0.16% to 0.56%). Total complications (1.11% vs
      1.00%, P = 0.618) and major morbidity and mortality (0.27% vs 0.33%, P = 0.581)
      did not differ between the 2 time periods. CONCLUSIONS: Anesthesia care for
      advanced endoscopy in a high-risk population significantly reduced sedation
      complications compared with nurse-administered sedation. Endoscopic complications
      were unchanged. The sedation risk reduction did not reduce major morbidity,
      mortality, or total complications.

PMID- 24859081
TI  - Homeostasis of the period of post-translational biochemical oscillators.
AB  - Generally, circadian clocks or biological oscillations are resistant to external
      conditions such as temperature and nutrient concentration. We propose that enzyme
      limited competition provides a general mechanism of homeostasis of the period of
      post-translational oscillators based on protein modifications, and demonstrate it
      by nutrient compensation in a theoretical model of cyanobacterial circadian
      clock. The rate change by nutrient concentration is counterbalanced by the amount
      of available free enzyme, which occurs because of the competition among the
      various substrates for the limited enzyme. The temperature and nutrient
      compensation are determined by the postulate that the catalytic modification
      reactions are rate limiting. 

PMID- 24859082
TI  - Functional characterization of a Plagiochasma appendiculatum flavone synthase I
      showing flavanone 2-hydroxylase activity.
AB  - FNS I is a 2-oxoglutarate dependent dioxygenase (2-ODD) found mainly in species
      of the Apiaceae family. Here, an FNS I cDNA sequence was isolated from the
      liverwort Plagiochasma appendiculatum (Aytoniaceae) and characterized. The
      recombinant protein exhibited high FNS I activity catalyzing the conversion of
      naringenin to apigenin and 2-hydroxynaringenin. The critical residue for
      flavanone-2-hydroxylation activity was Tyr240, as identified from homology
      modeling and site-directed mutagenesis. The recombinant protein also showed some
      flavonol synthase activity, as it can convert dihydrokaempferol to kaempferol.
      When the Leu311 residue was mutated to Phe, the enzyme's capacity to convert
      dihydrokaempferol to kaempferol was substantially increased. PaFNS I represents a
      2-ODD in which a hydrophobic pi-stacking interaction between the key residue and
      the naringenin A-ring determines 2-hydroxyflavanone formation. 

PMID- 24859083
TI  - Low expression level of OB-Rb results from constitutive translocational
      attenuation attributable to a less efficient signal sequence.
AB  - OB-Rb is a crucial factor for leptin signaling. This study was initially
      motivated by the observation that OB-Rb expression is constitutively inhibited in
      the early secretory pathway. Our analyses reveal that OB-Rb contains a less
      hydrophobic, but functionally active N-terminal signal sequence. Constitutive
      translocational attenuation attributable to a less efficient signal sequence
      proved to be a reason for low protein level of OB-Rb. By contrast, enhanced
      signal sequence efficiency rescues translocation and cell surface expression of
      OB-Rb, and eventually potentiates leptin signaling. These observations provide
      considerable insight into the therapeutic enhancement of OB-Rb translocation as a
      potential strategy for leptin resistance. 

PMID- 24859084
TI  - The crystal structure of arginyl-tRNA synthetase from Homo sapiens.
AB  - Arginyl-tRNA synthetase (ArgRS) is a tRNA-binding protein that catalyzes the
      esterification of L-arginine to its cognate tRNA. L-Canavanine, a structural
      analog of L-arginine, has recently been studied as an anticancer agent. Here, we
      determined the crystal structures of the apo, L-arginine-complexed, and L
      canavanine-complexed forms of the cytoplasmic free isoform of human ArgRS
      (hArgRS). Similar interactions were formed upon binding to L-canavanine or L
      arginine, but the interaction between Tyr312 and the oxygen of the oxyguanidino
      group was a little bit different. Detailed conformational changes that occur upon
      substrate binding were explained. The hArgRS structure was also compared with
      previously reported homologue structures. The results presented here may provide
      a basis for the design of new anticancer drugs, such as L-canavanine analogs.

PMID- 24859085
TI  - Tracking bacterial pathogens with genetically-encoded reporters.
AB  - During the infectious process, bacterial pathogens are subject to changes in
      environmental conditions such as nutrient availability, immune response
      challenges, bacterial density and physical contacts with targeted host cells.
      These conditions occur in the colonized organs, in diverse regions within
      infected tissues or even at the subcellular level for intracellular pathogens.
      Integration of environmental cues leads to measurable biological responses in the
      bacterium required for adaptation. Recent progress in technology enabled the
      study of bacterial adaptation in situ using genetically encoded reporters that
      allow single cell analysis or whole body imaging based on fluorescent proteins,
      alternative fluorescent assays or luciferases. This review presents a historical
      perspective and technical details on the methods used to develop transcriptional
      reporters, protein-protein interaction assays and secretion detection assays to
      study pathogenic bacteria adaptation in situ. Finally, studies published in the
      last 5 years on gram positive and gram negative bacterial adaptation to the host
      during infection are discussed. However, the methods described here could easily
      be extended to study complex microbial communities within host tissue and in the
      environment.

PMID- 24859087
TI  - DHTP is an allosteric inhibitor of the kinesin-13 family of microtubule
      depolymerases.
AB  - The kinesin-13 family of microtubule depolymerases is a major regulator of
      microtubule dynamics. RNA interference-induced knockdown studies have highlighted
      their importance in many cell division processes including spindle assembly and
      chromosome segregation. Since microtubule turnovers and most mitotic events are
      relatively rapid (in minutes or seconds), developing tools that offer faster
      control over protein functions is therefore essential to more effectively
      interrogate kinesin-13 activities in living cells. Here, we report the
      identification and characterization of a selective allosteric kinesin-13
      inhibitor, DHTP. Using high resolution microscopy, we show that DHTP is cell
      permeable and can modulate microtubule dynamics in cells. 

PMID- 24859088
TI  - Diverse small circular single-stranded DNA viruses identified in a freshwater
      pond on the McMurdo Ice Shelf (Antarctica).
AB  - Antarctica has some of the harshest environmental conditions for existence of
      life on Earth. In this pilot study we recovered eight diverse circular single
      stranded DNA (ssDNA) viral genome sequences (1904-3120 nts) from benthic mats
      dominated by filamentous cyanobacteria in a freshwater pond on the McMurdo Ice
      Shelf sampled in 1988. All genomes contain two to three major open reading frames
      (ORFs) that are uni- or bi-directionally transcribed and all have an ORF encoding
      a replication-associated protein (Rep). In one genome, the second ORF has
      similarity to a capsid protein (CP) of Nepavirus which is most closely related to
      geminiviruses. Additionally, all genomes have two intergenic regions that contain
      putative stem loop structures, six genomes have NANTATTAC as the nonanucleotide
      motif, while one has CCTTATTAC, and another has a non-canonical stem loop. In the
      large intergenic region, we identified iterative sequences flanking the putative
      stem-loop elements which are a hallmark of most circular ssDNA viruses encoding
      rolling circle replication (RCR) initiators of the HUH endonuclease superfamily.
      The Reps encoded by ssDNA viral genomes recovered in this study shared <38%
      pairwise identity to all other Reps of known ssDNA viruses. A previous study on
      Lake Limnopolar (Livingston Island, South Shetland Islands), using next
      generation sequencing identified circular ssDNA viruses and their putative Reps
      share <35% pairwise identity to those from the viral genomes removed in this
      study. It is evident from our pilot study that the global diversity of ssDNA
      viruses is grossly underestimated and there is limited knowledge on ssDNA viruses
      in Antarctica.

PMID- 24859086
TI  - High-throughput single-molecule studies of protein-DNA interactions.
AB  - Fluorescence and force-based single-molecule studies of protein-nucleic acid
      interactions continue to shed critical insights into many aspects of DNA and RNA
      processing. As single-molecule assays are inherently low-throughput, obtaining
      statistically relevant datasets remains a major challenge. Additionally, most
      fluorescence-based single-molecule particle-tracking assays are limited to
      observing fluorescent proteins that are in the low-nanomolar range, as spurious
      background signals predominate at higher fluorophore concentrations. These
      technical limitations have traditionally limited the types of questions that
      could be addressed via single-molecule methods. In this review, we describe new
      approaches for high-throughput and high-concentration single-molecule biochemical
      studies. We conclude with a discussion of outstanding challenges for the single
      molecule biologist and how these challenges can be tackled to further approach
      the biochemical complexity of the cell. 

PMID- 24859089
TI  - The hierarchy of task decision and response selection: a task-switching event
      related potentials study.
AB  - According to "hierarchical" multi-step theories, response selection is preceded
      by a decision regarding which task rule should be executed. Other theories assume
      a "flat" single-step architecture in which task information and stimulus
      information are simultaneously considered. Using task switching, the authors
      independently manipulated two kinds of conflict: task conflict (with information
      that potentially triggers the relevant or the competing task rule/identity) and
      response conflict (with information that potentially triggers the relevant or the
      competing response code/motor response). Event related potentials indicated that
      the task conflict effect began before the response conflict effect and carried on
      in parallel with it. These results are more in line with the hierarchical view. 

PMID- 24859090
TI  - Slow wave maturation on a visual working memory task.
AB  - The purpose of the present study is to analyze how the Slow Wave develops in the
      retention period on a visual Delayed Match-to-Sample task performed by 170
      subjects between 6 and 26 years old, divided into 5 age groups. In addition, a
      neuropsychological test (Working Memory Test Battery for Children) was correlated
      with this Event Related Potential (ERP) in order to observe possible
      relationships between Slow Wave maturation and the components of Baddeley and
      Hitch's Working Memory model. The results showed a slow negativity during the
      retention period in the posterior region in all the age groups, possibly
      resulting from sustained neural activity related to the visual item presented. In
      the anterior region, a positive slow wave was observed in the youngest subjects.
      Dipole analysis suggests that this fronto-central positivity in children (6-13
      years old) consists of the positive side of the posterior negativity, once these
      subjects only needed two posterior dipoles to explain almost all the neural
      activity. Negative correlations were shown between the Slow Wave and the Working
      Memory Test Battery for Children, indicating a commonality in assessing Working
      Memory with the Slow Wave and the neuropsychological testing.

PMID- 24859091
TI  - Neural correlates of social perception on response bias.
AB  - Accurate person perception is crucial in social decision-making. One of the
      central elements in successful social perception is the ability to understand
      another's response bias; this is because the same behavior can represent
      different inner states depending on whether other people are yea-sayers or
      naysayers. In the present study, we have tried to investigate how the internal
      biases of others are perceived. Using a multi-trial learning paradigm, perceivers
      made predictions about a target's responses to various suggested activities and
      then received feedback for each prediction trial-by-trial. Our hypotheses were
      that (1) the internal decision criterion of the targets would be realized through
      repeated experiences, and (2) due to positive-negative asymmetry, yea-sayers
      would be recognized more gradually than naysayers through the probabilistic
      integration of repeated experiences. To find neural evidence that tracks
      probabilistic integration when forming person knowledge on response biases, we
      employed a model-based fMRI with a State-Space Model. We discovered that person
      knowledge about yea-sayers modulated several brain regions, including caudate
      nucleus, DLPFC, hippocampus, etc. Moreover, when person knowledge was updated
      with incorrect performance feedback, brain regions including the caudate nucleus,
      DLPFC, dmPFC, and TPJ were also involved. There were overlapping regions for both
      processes, caudate nucleus and DLPFC, suggesting that these regions take crucial
      roles in forming person knowledge with repeated feedback, while reflecting
      acquired information up to the current prediction. 

PMID- 24859092
TI  - Increased expression of Lgr5 is associated with chemotherapy resistance in human
      gastric cancer.
AB  - Leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5), a marker of
      adult stem cells and cancer stem cells, plays important roles in tumor
      progression. Furthermore, Lgr5 also contributes to chemoradiotherapy resistance.
      However, the function of Lgr5 in the prediction of preoperative chemotherapy
      efficacy has not been reported. We evaluated the potential of Lgr5 in predicting
      tumor response and overall survival in advanced gastric cancer treated with
      preoperative chemotherapy. The association between Lgr5 and chemotherapy
      resistance was also investigated in gastric cancer cell lines. Hematoxylin and
      eosin staining and immunohistochemical analysis of Lgr5 expression were performed
      in 68 cases of gastric cancer treated with preoperative chemotherapy. Lgr5
      expression was specifically silenced in the AGS gastric cancer cell lines by RNA
      interference. Levels of Lgr5 mRNA and protein in cell lines were detected by
      quantitative reverse transcription-polymerase chain reaction or western blotting.
      Cell viability was evaluated by an MTT assay. Cell apoptosis was assessed by
      Annexin V-FITC/propidium iodide dual staining analysis. We found that Lgr5
      expression was significantly associated with tumor regression grade after
      preoperative chemotherapy. The rate of positive Lgr5 expression was significantly
      higher in patients with poor tumor regression compared with those exhibiting
      tumor regression (P=0.001). Lgr5-positive patients had a significantly shorter
      survival time than Lgr5-negative patients (P=0.001). Inhibition of Lgr5
      expression with small interfering RNA increased the sensitivity of AGS gastric
      cancer cells to chemotherapy. Our findings suggest that Lgr5 expression may be
      implicated in the chemoresistance of gastric cancer cells and is a potential
      novel biomarker for predicting response to chemotherapy and prognosis in gastric
      cancer patients, and may also represent a potential new therapeutic target for
      cancer therapy.

PMID- 24859098
TI  - Building partnerships with rural Arkansas faith communities to promote veterans'
      mental health: lessons learned.
AB  - BACKGROUND: The Mental Health-Clergy Partnership Program established partnerships
      between institutional (Department of Veterans' Affairs [VA] chaplains, mental
      health providers) and community (local clergy, parishioners) groups to develop
      programs to assist rural veterans with mental health needs. OBJECTIVES: Describe
      the development, challenges, and lessons learned from the Mental Health-Clergy
      Partnership Program in three Arkansas towns between 2009 and 2012. METHODS:
      Researchers identified three rural Arkansas sites, established local advisory
      boards, and obtained quantitative ratings of the extent to which partnerships
      were participatory. RESULTS: Partnerships seemed to become more participatory
      over time. Each site developed distinctive programs with variation in fidelity to
      original program goals. Challenges included developing trust and maintaining
      racial diversity in local program leadership. CONCLUSIONS: Academics can partner
      with local faith communities to create unique programs that benefit the mental
      health of returning veterans. Research is needed to determine the effectiveness
      of community based programs, especially relative to typical "top-down" outreach
      approaches.

PMID- 24859099
TI  - Reconciling traditional knowledge, food security, and climate change: experience
      from Old Crow, YT, Canada.
AB  - BACKGROUND: Because of a lack of transportation infrastructure, Old Crow has the
      highest food costs and greatest reliance on traditional food species for
      sustenance of any community in Canada's Yukon Territory. Environmental, cultural,
      and economic change are driving increased perception of food insecurity in Old
      Crow. OBJECTIVES: To address community concerns regarding food security and
      supply in Old Crow and develop adaptation strategies to ameliorate their impact
      on the community. METHODS: A community adaptation workshop was held on October
      13, 2009, in which representatives of different stakeholders in the community
      discussed a variety of food security issues facing Old Crow and how they could be
      dealt with. Workshop data were analyzed using keyword, subject, and narrative
      analysis techniques to determine community priorities in food security and
      adaptation. RESULTS: Community concern is high and favored adaptation options
      include agriculture, improved food storage, and conservation through increased
      traditional education. These results were presented to the community for review
      and revision, after which the Vuntut Gwitchin Government will integrate them into
      its ongoing adaptation planning measures.

PMID- 24859101
TI  - Utilization of an interorganizational network analysis to evaluate the
      development of community capacity among a community-academic partnership.
AB  - BACKGROUND: Following a community health assessment the Brazos Valley Health
      Partnership (BVHP) organized to address fragmentation of services and local
      health needs. This regional partnership employs the fundamental principles of
      community-based participatory research, fostering an equitable partnership with
      the aim of building community capacity to address local health issues.
      OBJECTIVES: This article describes changes in relationships as a result of
      capacity building efforts in a community-academic partnership. Growth in network
      structure among organizations is hypothesized to be indicative of less
      fragmentation of services for residents and increased capacity of the BVHP to
      collectively address local health issues. METHODS: Each of the participant
      organizations responded to a series of questions regarding its relationships with
      other organizations. Each organization was asked about information sharing, joint
      planning, resource sharing, and formal agreements with other organizations. The
      network survey has been administered 3 times between 2004 and 2009. RESULTS:
      Network density increased for sharing information and jointly planning events.
      Growth in the complexity of relationships was reported for sharing tangible
      resources and formal agreements. The average number of ties between organizations
      as well as the strength of relationships increased. CONCLUSION: This study
      provides evidence that the community capacity building efforts within these
      communities have contributed to beneficial changes in interorganizational
      relationships. Results from this analysis are useful for understanding how a
      community partnership's efforts to address access to care can strengthen a
      community's capacity for future action. Increased collaboration also leads to new
      assets, resources, and the transfer of knowledge and skills.

PMID- 24859100
TI  - Brentwood community health care assessment.
AB  - BACKGROUND: The Community Alliance for Research Empowering Social Change (CARES)
      is an academic-community research partnership designed to train community members
      on research methods and develop the infrastructure for community-based
      participatory research (CBPR) to examine and address racial/ethnic health
      disparities. The Brentwood Community Health Assessment (BCHA) was developed
      through a CBPR pilot project grant from CARES. OBJECTIVES: The purpose of the
      BCHA is to assess health care utilization and identify existing barriers to
      health care access among a multi-ethnic community in the Hamlet of Brentwood, New
      York. METHODS: Using CBPR approaches, the community-academic research partnership
      develop the study design and survey instrument. Trained Bilingual
      (English/Spanish) data collectors verbally administered surveys door-to-door to
      residents of Brentwood from October 2010 to May 2011. Inclusion criteria required
      participants to be at least 18 years of age and speak either English or Spanish.
      RESULTS: Overall, 232 residents completed the BCHA; 49% were male, 66% Hispanic,
      13% non-Hispanic White, 13% non-Hispanic Black, 29% had less than a high school
      education, and 33% were born in United States. The assessment results revealed
      that most residents are able to access health care when needed and the most
      significant barriers to health care access are insurance and cost. CONCLUSIONS:
      We describe the community-academic partnered process used to develop and
      implement the BCHA and report assessment findings; the community-partnered
      approach improved data collection and allowed access into one of Suffolk County's
      most vulnerable communities.

PMID- 24859102
TI  - Capacity needs in community-based organizations for enhancing translational
      research in Puerto Rico.
AB  - BACKGROUND: In an effort to form and sustain community-academic partnerships
      (CAPs) to enhance clinical and translational research, an assessment of needs for
      selecting and implementing evidence-based programs (EBPs) was conducted among a
      group of community-based organizations (CBOs) throughout Puerto Rico. METHODS:
      The survey was based on an instrument developed by the Cancer Prevention and
      Control Research Network. It assessed specific service information, program
      selection/implementation processes, knowledge and perception of EBPs, funding
      venues, evaluation processes, and capacity and training needs. Recruitment
      consisted of contacting 100 nonprofit organizations in Puerto Rico that work or
      address specific health areas, namely, cancer, neurological disorders, HIV, and
      cardiovascular health. RESULTS: The survey revealed wide variability in
      understanding what constitutes an EBP. Training needs for building a productive
      translational research process also were identified. Prominent among these were
      securing funding for ongoing operations, utilizing data for decision making,
      developing collaborations, managing information, conducting community needs
      assessments, and program evaluation. CONCLUSIONS: These findings point to
      important implications for promoting community-campus partnerships for advancing
      clinical and translational research.

PMID- 24859103
TI  - Refining the research infrastructure at community health centers.
AB  - BACKGROUND: Community health centers (CHC) often partner with academics to
      conduct community-based participatory research (CBPR). Because of their research
      expertise, academic partners are usually the principal investigators (PIs);
      however, moving the home base of research to the community can prove beneficial
      to the CHC and its community. OBJECTIVES: The purpose of this paper was to
      discuss the lessons learned after conducting a CBPR project and to share
      identified solutions. METHODS: A longitudinal perinatal risk reduction
      intervention study was conducted with primiparous Native Hawaiian women receiving
      prenatal care at a CHC. The intervention incorporated home visiting, social
      support, and lactation management. RESULTS: Primary lessons learned from this
      participatory process can be grouped into infrastructure, human resources, and
      recruitment. CONCLUSIONS: Sharing lessons learned can serve to expand a CHC's
      involvement in research, and provide a venue for discovering innovative and
      viable community and practice based approaches to solving health disparity
      challenges.

PMID- 24859105
TI  - Community-campus partnership in action: lessons learned from the DuPage County
      Patient Navigation Collaborative.
AB  - BACKGROUND: Using community-based participatory research (CBPR), the DuPage
      County Patient Navigation Collaborative (DPNC) developed an academic campus
      community research partnership aimed at increasing access to care for underserved
      breast and cervical cancer patients within DuPage County, a collar county of
      Chicago. Given rapidly shifting demographics, targeting CBPR initiatives among
      underserved suburban communities is essential. OBJECTIVES: To discuss the
      facilitating factors and lessons learned in forging the DPNC. METHODS: A patient
      navigation collaborative was formed to guide medically underserved women through
      diagnostic resolution and if necessary, treatment, after an abnormal breast or
      cervical cancer screening. LESSONS LEARNED: Facilitating factors included (1)
      fostering and maintaining collaborations within a suburban context, (2) a systems
      based participatory research approach, (3) a truly equitable community-academic
      partnership, (4) funding adaptability, (5) culturally relevant navigation, and
      (6) emphasis on co-learning and capacity building. CONCLUSIONS: By highlighting
      the strategies that contributed to DPNC success, we envision the DPNC to serve as
      a feasible model for future health interventions.

PMID- 24859106
TI  - Community-partnered research conference model: the experience of Community
      Partners in Care study.
AB  - THE PROBLEM: Conducting community-partnered research conferences is a powerful
      yet underutilized approach to translating research into practice and improving
      result dissemination and intervention sustainability strategies. Nonetheless,
      detailed descriptions of conference features and ways to use them in empirical
      research are rare. PURPOSE: We describe how community-partnered conferences may
      be integrated into research projects by using an example of Community Partners in
      Care (CPIC), a large, cluster-randomized, controlled, trial (RCT) that uses
      community-partnered participatory research (CPPR) principles. KEY POINTS: Our
      conceptual model illustrates the role community-partnered research conferences
      may play in three study phases and describes how different conference features
      may increase community engagement, build two-way capacity, and ensure equal
      project ownership. CONCLUSIONS: As the number of community-partnered studies
      grows, so too does the need for practical tools to support this work. Community
      partnered research conferences may be effectively employed in translational
      research to increase two-way capacity building and promote long-term intervention
      success.

PMID- 24859107
TI  - Improving treatment for opioid dependence: a perspective from the Ohio Valley
      node of the NIDA Clinical Trials Network.
AB  - PROBLEM: Rates of adoption of evidenced-based practices, including the use of
      medications, to treat opioid dependence are low and severely limit secondary
      prevention efforts to curtail the prescription drug epidemic. PURPOSE: The goal
      of this article was to describe how involvement in a research clinical trials
      network (CTN) facilitated the adoption of medications to treat opioid dependence
      at two community-based treatment programs (CTPs) affiliated with the Ohio Valley
      Node (OVN) of the National Institute on Drug Abuse's (NIDA) CTN. KEY POINTS:
      Participation in a CTN may facilitate adoption by providing the infrastructure
      for trialability and observability, but the most critical function may be the
      knowledge translation that occurs through the individual-level professional
      relationships that develop. CONCLUSION: Community-based treatment providers'
      involvement in research networks may increase the rate of evidence-based practice
      (EBP) adoption and improve outcomes for patients with opioid dependence.

PMID- 24859108
TI  - Standardizing a process to engage African Americans in health research: the
      Community Research Outreach Workers' Network (CROWN).
AB  - BACKGROUND: Recruiting African Americans into health research studies has proven
      to be challenging. Barriers to research study participation exist at the
      individual, research, and community levels. Additionally, a gap may exist where
      research opportunities do not reach potential participants in many African
      American communities and/or research investigators may not have access to
      pathways that allow for them to connect with potential research participants.
      OBJECTIVES: Few studies have been published regarding an engagement strategy that
      utilizes volunteer research registries and community review boards to link
      registrants to health research. Therefore, the aims of this Community Research
      Outreach Workers' Network (CROWN) pilot project were to (1) create a community
      outreach-generated registry of African Americans interested in participating in
      health research and (2) develop a community research review board that serves to
      advise research investigators on conducting culturally engaging research.
      METHODS: The Uniformed Services University Center for Health Disparities (USUCHD)
      served as an administrative coordinating center that provided resources and
      support to a community research review board that determined if research
      investigators could recruit participants from the CROWN registry. RESULTS: The
      CROWN board reviewed five research studies and provided feedback to research
      investigators. In turn, 71 people who were recruited into research studies
      reported that they heard about the study through CROWN. CONCLUSIONS: Outcomes
      from this pilot project suggest that the CROWN model is an effective strategy
      that can be used to engage African Americans in health research.

PMID- 24859110
TI  - Examining Benefits of Academic-Community Research Team Training: Rochester's
      Suicide Prevention Training Institutes.
AB  - BACKGROUND: Although community-engaged research (CER), including community-based
      participatory research (CBPR), is a growing approach in addressing health
      disparities, little scientific study on how to enhance its processes or products
      exists. These fields are built on practice-based case studies, evaluations, and
      qualitative examinations of principles in action. This gap is as an emerging
      priority in the clinical and translation sciences. OBJECTIVES: We designed a 5
      day workshop for academic-community research teams in suicide prevention and
      health promotion, broadly defined. Seasoned academic and community partners
      developed and implemented curriculum at three training institutes from 2007 to
      2010. We developed self-report tools to evaluate this training model for CER
      practice. We crafted and evaluated both mediating processes and outcome measures
      for academic and community partners to assess team CER development. METHODS: We
      analyzed post-training evaluation surveys completed late in 2010. We conducted
      exploratory factor analysis on survey data from 48 community or academic
      partners. These team members participated in at least one National Institutes of
      Health-funded CER training institute to advance suicide prevention, broadly
      defined. CONCLUSIONS: Partnership development measures that capture both academic
      and community perspectives demonstrate reliability and validity. Multidimensional
      latent constructs for inclusion in CER development models included partnership
      agency, personal knowledge and capacities, and benefits of collaborative research
      partnerships over time. We discuss the utility of findings to future CER training
      design and study.

PMID- 24859109
TI  - Colorado Immersion Training in Community Engagement: Because You Can't Study What
      You Don't Know.
AB  - BACKGROUND: Community engagement (CE)has become a major element in medical
      research. In alliance with the goals of the Clinical and Translational Sciences
      Award program, Colorado Immersion Training in Community Engagement (CIT) is a
      community-campus partnership that aims to introduce an expanded pool of
      researchers to community-based participatory research (CBPR) and CE. OBJECTIVES:
      To describe CIT components and preliminary results. METHODS: CIT attempts to
      support a change in the research trajectory of academic health researchers,
      program developers, and graduate students toward CE. The program occurs on campus
      and in six community settings: Urban African American, urban Asian and refugee,
      urban Latino, urban American Indian/Alaska Native, rural northeast Colorado, and
      rural San Luis Valley. Components include a 4-week Directed Reading, a seminar on
      CBPR, 4-day community immersion, reflection, and 6-month support. Evaluation
      describes recruitment, implementation, and participants' understanding of CBPR
      and skills post-training. RESULTS: Fifty-eight people have participated. A
      comprehensive curriculum was developed to address (1) principals of CBPR, (2)
      health disparities, (3) listening to community, (4) self-reflection, and (5)
      engagement tools. Community immersions expose participants to a community's
      culture and opportunities to discuss health issues with a range of community
      members. Local "community guides" enhance participants' experience. Of the first
      two cohorts, 90% changed the way they plan to approach their research, 94%
      changed how they viewed community involvement in research, and 77% learned new
      skills to help engage communities in research. CONCLUSIONS: CIT applies to and
      positively impacts researchers from a variety of disciplines. CIT creates
      opportunities for long lasting partnerships between researchers and communities.

PMID- 24859111
TI  - Participation and detection rates by age and sex for colonoscopy versus fecal
      immunochemical testing in colorectal cancer screening.
AB  - PURPOSE: To compare two strategies for colorectal cancer screening: one-time
      colonoscopy versus fecal immunochemical testing (FIT) (and colonoscopy for
      positive) every 2 years, in order to determine which strategy provides the
      highest participation and detection rates in groups of sex and age. METHODS: This
      analysis was performed with data from the first screening round within the
      COLONPREV study, a population-based, multicenter, nationwide trial carried out in
      Spain. Several logistic regression models were applied to identify the influence
      of the screening test on participation rates and detection of proximal and distal
      neoplasms, as well to identify the influence of age and sex: women aged 50-59
      years, women aged 60-69 years, men aged 50-59 years, and men aged 60-69 years.
      RESULTS: Participation was higher in women than in men, especially among women
      aged 50-59 years (25.91 % for colonoscopy and 35.81 % for FIT). Crossover from
      colonoscopy to FIT was higher among women than men, especially among those aged
      60-69 years (30.37 %). In general, detection of any neoplasm and advanced adenoma
      was higher with colonoscopy than with FIT, but no significant differences were
      found between the two strategies for colorectal cancer detection. Detection of
      advanced adenoma in both arms was lower in women [specifically in women aged 50
      59 years (OR 0.31; 95 % CI 0.25-0.38) than in men aged 60-69 years]. Women aged
      50-59 years in the colonoscopy arm had a higher probability of detection of
      advanced adenoma (OR 4.49; 95 % CI 3.18-6.35), as well as of detection of
      neoplasms in proximal and distal locations (proximal OR 19.34; 95 % CI 12.07
      31.00; distal OR 11.04; 95 % CI 8.13-15.01) than women of the same age in the FIT
      arm. These differences were also observed in the remaining groups but to a lesser
      extent. CONCLUSION: Women were more likely to participate in a FIT-based
      strategy, especially those aged 50-59 years. The likelihood of detection of any
      neoplasm was higher in the colonoscopy arm for all the population groups studied,
      especially in women aged 50-59 years. Distinct population groups should be
      informed of the benefits of each screening strategy so that they may take
      informed decisions.

PMID- 24859112
TI  - Young children's food brand knowledge. Early development and associations with
      television viewing and parent's diet.
AB  - Brand knowledge is a prerequisite of children's requests and choices for branded
      foods. We explored the development of young children's brand knowledge of foods
      highly advertised on television - both healthy and less healthy. Participants
      were 172 children aged 3-5 years in diverse socio-economic settings, from two
      jurisdictions on the island of Ireland with different regulatory environments.
      Results indicated that food brand knowledge (i) did not differ across
      jurisdictions; (ii) increased significantly between 3 and 4 years; and (iii)
      children had significantly greater knowledge of unhealthy food brands, compared
      with similarly advertised healthy brands. In addition, (iv) children's healthy
      food brand knowledge was not related to their television viewing, their mother's
      education, or parent or child eating. However, (v) unhealthy brand knowledge was
      significantly related to all these factors, although only parent eating and
      children's age were independent predictors. Findings indicate that effects of
      food marketing for unhealthy foods take place through routes other than
      television advertising alone, and are present before pre-schoolers develop the
      concept of healthy eating. Implications are that marketing restrictions of
      unhealthy foods should extend beyond television advertising; and that family
      focused obesity prevention programmes should begin before children are 3 years of
      age. 

PMID- 24859113
TI  - Japanese consumers' valuation of domestic beef after the Fukushima Daiichi
      Nuclear Power Plant accident.
AB  - After the radioactive contamination of agricultural and livestock products caused
      by the Fukushima Daiichi Nuclear Power Plant accident of March 11, 2011, consumer
      aversion against purchasing food products from the affected areas has become a
      major social problem in Japan. We examine how test results for radioactive
      materials in beef affect consumer valuation of beef produced in no-risk and
      affected areas using a choice experiment survey of consumers in the Tokyo
      metropolitan area (N = 392). Respondents were divided into two groups: one faced
      choice experiment tasks under the current test condition (the test status was
      only "under the limit"), and the other faced choice experiment tasks under the
      tightened test condition (with three levels: "below the limit," "below one-tenth
      of the limit," and "undetected"). We found that consumer valuation of "below the
      limit" beef in the affected area did not differ from that of "below one-tenth of
      the limit" beef in the affected area. Introducing the tightened status improved
      consumer valuations of all types of beef in the no-risk area regardless of the
      test status. However, consumer valuation of "undetected" beef in the affected
      area was lower than that in the no-risk area. The same measures need to be
      implemented with great care in both no-risk and affected areas. Otherwise, the
      effects of measures taken in the affected areas may be diluted. 

PMID- 24859114
TI  - Effect of glycemic load on eating behavior self-efficacy during weight loss.
AB  - High eating behavior self-efficacy may contribute to successful weight loss. Diet
      interventions that maximize eating behavior self-efficacy may therefore improve
      weight loss outcomes. However, data on the effect of diet composition on eating
      behavior self-efficacy are sparse. To determine the effects of dietary glycemic
      load (GL) on eating behavior self-efficacy during weight loss, body weight and
      eating behavior self-efficacy were measured every six months in overweight adults
      participating in a 12-mo randomized trial testing energy-restricted diets
      differing in GL. All food was provided during the first six months and self
      selected thereafter. Total mean weight loss did not differ between groups, and GL
      level had no significant effect on eating behavior self-efficacy. In the combined
      cohort, individuals losing the most weight reported improvements in eating
      behavior self-efficacy, whereas those achieving less weight loss reported
      decrements in eating behavior self-efficacy. Decrements in eating behavior self
      efficacy were associated with subsequent weight regain when diets were self
      selected. While GL does not appear to influence eating behavior self-efficacy,
      lesser amounts of weight loss on provided-food energy restricted diets may deter
      successful maintenance of weight loss by attenuating improvements in eating
      behavior self-efficacy. 

PMID- 24859115
TI  - Long range regulation of the sonic hedgehog gene.
AB  - The regulatory architecture that controls developmental genes is often a
      collection of enhancers that, in combination, generate a complex spatial and
      temporal pattern of expression. These enhancers populate domains operating at
      long distances and, in the case of the sonic hedgehog (Shh) locus, this
      regulatory domain covers ~900-1000kb. Within this context each embryonic tissue
      that expresses Shh has acquired its own regulatory apparatus which may require
      the activity from several distinct enhancers. Expression of Shh in the developing
      limb bud is driven by a single enhancer that interprets a myriad of genetic
      information to initiate expression in the posterior margin of the limb bud,
      inhibits expression along the anterior margin, defines the level of expression,
      and sets the tissue boundary of expression. 

PMID- 24859117
TI  - [A structural model for the practice of life safety behavior in school-age
      children].
AB  - PURPOSE: This study is an examination of the paths in which the primary factors
      of anxiety, impulsiveness, knowledge of life safety practice, attitudes towards
      life safety practice, interpersonal support, and self-efficacy from Pender's
      Health Promotion Model influence the practice of life safety behavior in school
      age children. METHODS: The sample consisted of 489 5th and 6th grade students
      recruited from five elementary schools in Seoul City and four provinces, South
      Korea. Data were analyzed using descriptive statistics, correlations, factor
      analysis, and structural equation modeling. RESULTS: Attitudes towards life
      safety practice, interpersonal support, self-efficacy and impulsiveness directly
      influenced practice of life safety behavior. Anxiety did not have a direct
      influence on practice of life safety behavior, but indirectly affected it. In
      this modified model, 52.0% of the practice of life safety behavior was explained
      by the primary factors. CONCLUSION: To facilitate the practice life safety
      behaviors in late childhood, a positive attitude towards life safety needs to be
      developed along with decreasing impulsiveness and enhancing self-efficacy.

PMID- 24859118
TI  - [Development of critical thinking skill evaluation scale for nursing students].
AB  - PURPOSE: To develop a Critical Thinking Skill Test for Nursing Students. METHODS:
      The construct concepts were drawn from a literature review and in-depth
      interviews with hospital nurses and surveys were conducted among students (n=607)
      from nursing colleges. The data were collected from September 13 to November 23,
      2012 and analyzed using the SAS program, 9.2 version. The KR 20 coefficient for
      reliability, difficulty index, discrimination index, item-total correlation and
      known group technique for validity were performed. RESULTS: Four domains and 27
      skills were identified and 35 multiple choice items were developed. Thirty
      multiple choice items which had scores higher than .80 on the content validity
      index were selected for the pre test. From the analysis of the pre test data, a
      modified 30 items were selected for the main test. In the main test, the KR 20
      coefficient was .70 and Corrected Item-Total Correlations range was .11-.38.
      There was a statistically significant difference between two academic systems
      (p=.001). CONCLUSION: The developed instrument is the first critical thinking
      skill test reflecting nursing perspectives in hospital settings and is expected
      to be utilized as a tool which contributes to improvement of the critical
      thinking ability of nursing students.

PMID- 24859116
TI  - An allosteric switch for pro-HGF/Met signaling using zymogen activator peptides.
AB  - Stimulation of hepatocyte growth factor (HGF) signaling through the Met receptor
      is an attractive approach for promoting tissue repair and preventing fibrosis.
      Using structure-guided peptide phage display combined with an activity-based
      sorting strategy, we engineered allosteric activators of zymogen-like pro-HGF to
      bypass proteolytic activation and reversibly stimulate pro-HGF signaling through
      Met. Biochemical, structural and biological data showed that zymogen activator
      peptides (ZAPtides) potently and selectively bind the activation pocket within
      the serine protease-like beta-chain of pro-HGF and display titratable activation
      of pro-HGF-dependent Met signaling, leading to cell survival and migration. To
      further demonstrate the versatility of our ZAPtide platform, we identified
      allosteric activators for pro-macrophage stimulating protein and a zymogen serine
      protease, Protein C, which also provides evidence for target selectivity. These
      studies reveal that ZAPtides use molecular mimicry of the trypsin-like N-terminal
      insertion mechanism and establish a new paradigm for selective pharmacological
      activation of plasminogen-related growth factors and zymogen serine proteases. 

PMID- 24859119
TI  - [A path analysis on factors influencing second primary cancer screening practices
      in stomach, colon, and breast cancer survivors].
AB  - PURPOSE: This study was conducted to identify the factors influencing second
      primary cancer (SPC) screening practice by examining the relationships of
      physical symptoms, knowledge and attitudes regarding SPC screening, perceived
      risk, primary cancer type, and demographic factors of cancer survivors. METHODS:
      Participants were 308 survivors of stomach, colon, or breast cancer recruited
      from 2 university hospitals in Korea. Data were collected using a questionnaire
      and analyzed using IBM SPSS 21.0 and AMOS 18.0. RESULTS: The proportion of
      participants taking all cancer screenings according to national guidelines was
      40%. They had moderate knowledge and a relatively positive attitude regarding SPC
      screening and high cancer risk perception. The participants had taken fewer SPC
      screenings after than before cancer diagnosis. The factors influencing cancer
      risk perception were age, physical symptoms, knowledge regarding SPC and primary
      cancer type (stomach). The factors influencing SPC screening practice were age,
      gender, economic status, knowledge regarding SPC screening, and primary cancer
      types (colon). CONCLUSION: It is important for clinical professionals to
      recognize that survivors of cancer are susceptible to another cancer. Education
      on SPC screening for these survivors should focus on communicating with and
      encouraging them to have regular cancer screenings.

PMID- 24859120
TI  - [Effects of open or closed suctioning on lung dynamics and hypoxemia in
      mechanically ventilated patients].
AB  - PURPOSE: This study was conducted to compare effects of open and closed
      suctioning methods on lung dynamics (dynamic compliance, tidal volume, and airway
      resistance) and hypoxemia (oxygen saturation and heart rate) in mechanically
      ventilated patients. METHODS: This study was a cross-over repeated design.
      Participants were 21 adult patients being treated with endotracheal intubation
      using a pressure-controlled ventilator below Fraction of Inspired Oxygen (FiO2)
      60% and PEEP 8 cmH2O. Data were collected at baseline and 1, 2, 3, 4, 5, and 10
      minutes after suctioning. Data were analyzed using two-factor ANOVA with repeated
      measures on time and suctioning type. RESULTS: Effects of the interaction between
      suction type and time were significant for oxygen saturation and heart rate but
      not significant for dynamic compliance, tidal volume, or airway resistance. Prior
      to performance of suctioning, tidal volume and oxygen saturation were
      significantly lower, but airway pressure and heart rate were significantly higher
      using the closed suctioning method as compared with the open suctioning method.
      CONCLUSION: For patients on ventilator therapy below FiO2 60% and PEEP 8cmH2O,
      open suctioning performed after delivery of 100% FiO2 using a mechanical
      ventilator may not have as much negative impact on lung dynamics and hypoxemia as
      closed suctioning.

PMID- 24859121
TI  - [Structural equation modeling on contraception behavior of unmarried men and
      women in Korea: gender difference].
AB  - PURPOSE: The purpose of this study was to test and validate a model to predict
      contraception behavior in unmarried men and women. METHODS: Data were collected
      from a questionnaire survey of 180 unmarried men and 186 unmarried women 20 years
      of age or over who had sexual relationships in the past 6 months. Participants
      were from Seoul, Kyunggi, Daegu, and Busan and data collection was done from
      February 19 to April 16, 2013. RESULTS: Model fit indices for the hypotheoretical
      model fitted to the recommended levels. Out of 15 paths, 11 were statistically
      significant in both. Predictors of contraception behavior in unmarried men and
      women were intention to use contraception and self-efficacy for contraception.
      Exposure to sexual content was directly significant to the intention in men only.
      Self-efficacy for contraception was affected by perceived threat of pregnancy and
      gender role attitude. In women, the two predictors were also significant except
      for the effect of exposure to sexual contents. CONCLUSION: Results indicate that
      an intervention program which increases self-efficacy in unmarried men and women
      contributes to effective contraception behavior. In addition, proper sexual
      education programs using positive aspect of mass media can help develop active
      participation for contraception behavior.

PMID- 24859122
TI  - [Development and evaluation of breastfeeding promotion program for mothers with
      breast engorgement following cesarean birth].
AB  - PURPOSE: This study was to develop a breastfeeding promotion program and to test
      effects of the program on levels of breast discomfort, breast size, sodium in
      breast milk, and type of feeding in mothers with breast engorgement following
      cesarean birth. METHODS: A non-synchronized non-equivalent control group pretest
      posttest design was used in this study. The participants were 70 postpartum
      mothers who were admitted to a postpartum care center and experienced breast
      engorgement following cesarean birth. The planned nursing intervention was the
      breastfeeding promotion program consisting of breast massage and 1:1
      breastfeeding education, counseling, and support focusing on individualized
      problem solving provided for 10 days. Fifty-three women completed the program
      (experimental group 26, control group, 27). Measurements were level of breast
      discomfort, breast size, sodium in breast milk and type of feeding at pre and
      posttest. RESULTS: Women who participated in the program experienced lower scores
      for breast discomfort, greater decrease in breast size, lower levels of sodium in
      breast milk, and practiced breastfeeding more than those in the control group.
      CONCLUSION: Results indicate that this breastfeeding promotion program is
      effective in reducing breast engorgement and improving breastfeeding practices,
      and is therefore recommended to enhance breastfeeding promotion practice in
      postpartum care centers.

PMID- 24859123
TI  - [A structural model for health risk behavior of late adolescents: based on 2010
      Korea Adolescent Health Survey].
AB  - PURPOSE: This study was done to construct and test a structural model to explain
      health risk behavior of late adolescents. METHODS: Data for this study were
      secondary data from the 2010 Korea Adolescent Health Survey based and 3,675 high
      school students who participated. Data were analyzed using SPSS 18.0 and AMOS
      19.0 programs. RESULTS: After 7 lines were removed, fitness statistics for the
      hypothetical model were appropriate (chi2=559.13, p<.001, GFI=.98, SRMR=.03,
      RMSEA=.04, NFI=.88, IFI=.90, CFI=.90, TLI=.86, AIC=671.13). The result showed
      that drinking-smoking is directly affected by 5 variables (32.5%), obesity is
      directly affected by 2 variables (0.7%), lack of physical activity is directly
      affected by 5 variables (22.2%), skipping of breakfast is directly affected by 3
      variables (11.9%), improper sleep is directly affected by 3 variables (7.5%), and
      psychological adaptation is directly affected by 4 variables (26.8%). CONCLUSION:
      The results of this study, indicate that late adolescents' health risk behavior
      is affected by many factors with complicate correlations suggesting further study
      compare youth health risk behaviors in a variety of environments.

PMID- 24859124
TI  - [The effects of an asthma management education program for preschoolers].
AB  - PURPOSE: This study was conducted to develop an asthma management education
      program for preschool children using Roy's adaptation theory as a framework and
      examining the effects of this program on adaptation to asthma treatment. METHODS:
      A non-equivalent control group pre-post-test design was used with 43 preschool
      children diagnosed with asthma and required to be hospitalized for inhalation
      therapy. An intervention group (n=23) participated in the educational program and
      a control group (n=20) received regular treatment. The education program was
      conducted and evaluated from June 30 to October 31 2012, a maximum 3 times every
      24 hours during hospitalization. Two nurses conducted the program using the
      teaching method of Gagne and Briggs; instruction design theory through
      questionnaires to measure perception of disease, behavior of adaptation to
      treatment with inhalation therapy. RESULTS: Effects of asthma management
      education program; scores for face-pain rating decreased and time of adaptation
      to treatment increased significantly in the experimental group compared to the
      control group but no significant differences were found for perception of the
      disease's cause and treatment. CONCLUSION: Results indicate that the asthma
      management education program has positive effects on adaptation to asthma
      treatment of preschoolers.

PMID- 24859125
TI  - [Factors related to nurses' patient identification behavior and the moderating
      effect of person-organization value congruence climate within nursing units].
AB  - PURPOSE: This research was an empirical study designed to identify precursors and
      interaction effects related to nurses' patient identification behavior. A
      multilevel analysis methodology was used. METHODS: A self-report survey was
      administered to registered nurses (RNs) of a university hospital in South Korea.
      Of the questionnaires, 1114 were analyzed. RESULTS: The individual-level factors
      that had a significantly positive association with patient identification
      behavior were person-organization value congruence, organizational commitment,
      occupational commitment, tenure at the hospital, and tenure at the unit.
      Significantly negative group-level precursors of patient identification behavior
      were burnout climate and the number of RNs. Two interaction effects of the person
      organization value congruence climate were identified. The first was a group
      level moderating effect in which the negative relationship between the number of
      RNs and patient identification behavior was weaker when the nursing unit's value
      congruence climate was high. The second was a cross-level moderating effect in
      which the positive relationship between tenure at the unit and patient
      identification behavior was weaker when value congruence climate was high.
      CONCLUSION: This study simultaneously tested both individual-level and group
      level factors that potentially influence patient identification behavior and
      identified the moderating role of person-organization value congruence climate.
      Implications of these results are discussed.

PMID- 24859126
TI  - [Development and validity of workplace bullying in nursing-type inventory (WPBN
      TI)].
AB  - PURPOSE: The purpose of this study was to develop an instrument to assess
      bullying of nurses, and test the validity and reliability of the instrument.
      METHODS: The initial thirty items of WPBN-TI were identified through a review of
      the literature on types bullying related to nursing and in-depth interviews with
      14 nurses who experienced bullying at work. Sixteen items were developed through
      2 content validity tests by 9 experts and 10 nurses. The final WPBN-TI instrument
      was evaluated by 458 nurses from five general hospitals in the Incheon
      metropolitan area. SPSS 18.0 program was used to assess the instrument based on
      internal consistency reliability, construct validity, and criterion validity.
      RESULTS: WPBN-TI consisted of 16 items with three distinct factors (verbal and
      nonverbal bullying, work-related bullying, and external threats), which explained
      60.3% of the total variance. The convergent validity and determinant validity for
      WPBN-TI were 100.0%, 89.7%, respectively. Known-groups validity of WPBN-TI was
      proven through the mean difference between subjective perception of bullying. The
      satisfied criterion validity for WPBN-TI was more than .70. The reliability of
      WPBN-TI was Cronbach's alpha of .91. CONCLUSIONS: WPBN-TI with high validity and
      reliability is suitable to determine types of bullying in nursing workplace.

PMID- 24859127
TI  - [Validation of a modified early warning score to predict ICU transfer for
      patients with severe sepsis or septic shock on general wards].
AB  - PURPOSE: To assess whether the Modified Early Warning Score (MEWS) predicts the
      need for intensive care unit (ICU) transfer for patients with severe sepsis or
      septic shock admitted to general wards. METHODS: A retrospective chart review of
      100 general ward patients with severe sepsis or septic shock was implemented.
      Clinical information and MEWS according to point of time between ICU group and
      general ward group were reviewed. Data were analyzed using multivariate logistic
      regression and the area under the receiver operating characteristic curves with
      SPSS/WIN 18.0 program. RESULTS: Thirty-eight ICU patients and sixty-two general
      ward patients were included. In multivariate logistic regression, MEWS (odds
      ratio [OR] 2.02, 95% confidence interval [CI] 1.43-2.85), lactic acid (OR 1.83,
      95% CI 1.22-2.73) and diastolic blood pressure (OR 0.89, 95% CI 0.80-1.00) were
      predictive of ICU transfer. The sensitivity and the specificity of MEWS used with
      cut-off value of six were 89.5% and 67.7% for ICU transfer. CONCLUSION: MEWS is
      an effective predictor of ICU transfer. A clinical algorithm could be created to
      respond to high MEWS and intervene with appropriate changes in clinical
      management.

PMID- 24859128
TI  - [Outcomes of home monitoring after palliative cardiac surgery in infants with
      congenital heart disease].
AB  - PURPOSE: Common conditions, such as dehydration or respiratory infection can
      aggravate hypoxia and are associated with interstage mortality in infants who
      have undergone palliative surgery for congenital heart diseases. This study was
      done to evaluate the efficacy of a home monitoring program (HMP) in decreasing
      infant mortality. METHODS: Since its inception in May 2010, all infants who have
      undergone palliative surgery have been enrolled in HMP. This study was a
      prospective observational study and infant outcomes during HMP were compared with
      those of previous comparison groups. Parents were trained to measure oxygen
      saturation, body weight and feeding volume and to contact the hospital through
      the hotline for emergency situations. Telephone counseling was conducted by
      clinical nurse specialists every week post discharge. RESULTS: Forty-one infants
      were enrolled in HMP. Nine hundred telephone counseling sessions were conducted.
      Seventy-three infants required telephone triage with the most common conditions
      being gastrointestinal (50.7%) and respiratory symptoms (32.9%). With HMP
      intervention, interstage mortality decreased from 18.6% (8/43) to 9.8% (4/41)
      (chi2=1.15, p=.283). CONCLUSION: Results indicate that active measures and
      treatments using the HMP decrease mortality rates, however further investigation
      is required to identify various factors that contribute to hemodynamic
      complications during the interstage period.

PMID- 24859129
TI  - Glia ECM interactions are required to shape the Drosophila nervous system.
AB  - Organs are characterized by a specific shape that is often remodeled during
      development. The dynamics of organ shape is in particular evident during the
      formation of the Drosophila nervous system. During embryonic stages the central
      nervous system compacts, whereas selective growth occurs during larval stages.
      The nervous system is covered by a layer of surface glial cells that form the
      blood brain barrier and a thick extracellular matrix called neural lamella. The
      size of the neural lamella is dynamically adjusted to the growing nervous system
      and we show here that perineurial glial cells secrete proteases to remodel this
      matrix. Moreover, an imbalance in proteolytic activity results in an abnormal
      shape of the nervous system. To identify further components controlling nervous
      system shape we performed an RNAi based screen and identified the gene nolo,
      which encodes an ADAMTS-like protein. We generated loss of function alleles and
      demonstrate a requirement in glial cells. Mutant nolo larvae, however, do not
      show an abnormal nervous system shape. The only predicted off-target of the
      nolo(dsRNA) is Oatp30B, which encodes an organic anion transporting protein
      characterized by an extracellular protease inhibitor domain. Loss of function
      mutants were generated and double mutant analyses demonstrate a genetic
      interaction between nolo and Oatp30B which prevented the generation of maternal
      zygotic mutant larvae. 

PMID- 24859130
TI  - Human pluripotent stem cell strategies for age-related macular degeneration.
AB  - Age-related macular degeneration (AMD) is a leading cause of severe vision loss
      in the Western world and is increasing exponentially as the population ages.
      Despite enormous worldwide efforts, the earliest pathogenic pathways involved in
      AMD are still not fully understood. It is essential to develop research tools for
      effective modeling of AMD pathogenesis and for subsequent drug discovery and cell
      or molecular therapies. This review will focus on the current progress in human
      pluripotent stem cells for understanding and treating AMD.

PMID- 24859132
TI  - Towards developing a bilingual treatment summary and survivorship care plan
      responsive to Spanish language preferred breast cancer survivors.
AB  - BACKGROUND: Treatment summary and survivorship care plan studies are at the
      forefront of research priorities with precedence for ethnic minority inclusion.
      This preliminary study joined the advocacy, scientific, and medical communities
      to inform the development and evaluation of the Treatment Summary and
      Survivorship Care Plan (TSSCP-S) template targeted for Latino breast cancer
      patients (LCA). METHODS: The development of the TSSCP-S began as modifications to
      the American Society of Cancer Oncology (ASCO) (TSSCP-ASCO) template via a
      transcreation process informed by 12 LCA survivors/advocates, and evaluated by 10
      survivor/advocates and health professionals. The TSSCP-S template development was
      guided by the Shared Care, Psychooncology Models, and Contextual Model of Health
      Related Quality of Life. RESULTS: The bilingual TSSCP-S was independently
      evaluated by bilingual, survivor/advocates, and health professionals (n = 10).
      Preliminary analyses indicate that the TSSCP-S template was rated more favorably
      than the TSSCP-ASCO on the following domains: content (p = 0.02), clarity (p =
      0.02), utility (p = 0.04), cultural and linguistic responsiveness (p = 0.03), and
      socioecological responsiveness (p = 0.01). Evaluators noted that the TSSCP-S
      template was more patient-centered, and endorsed the acceptability as well as the
      potential utility and applicability of the bilingual TSSCP-S template to
      appropriately guide surveillance and follow-up care. CONCLUSIONS: Our findings
      indicate that the TSSCP-S achieved clinical, cultural, and linguistic
      responsiveness relevant to Latinos. Patient-centered TSSCP that are presented in
      a bilingual format are necessary to achieve the intended goals of TSSCP including
      appropriate patient information, education, and resources pertaining to their
      treatment, potential side effects, and recommended surveillance and follow-up
      care for English language limited patients. Additionally, our culturally
      responsive TSSCP-S development framework offers a model for TSSCP template
      development for targeted and underserved populations, including ethnic and
      linguistic minority cancer survivors. IMPLICATIONS FOR CANCER SURVIVORS: These
      data support the development and evaluation of a TSSCP targeted to an
      underserved, high-risk population, LCAs. Identifying methods to improve
      surveillance and follow-up guideline adherence may lead to improved clinical
      cancer outcomes and quality of life.

PMID- 24859131
TI  - Characterization of rubber tree microRNA in phytohormone response using large
      genomic DNA libraries, promoter sequence and gene expression analysis.
AB  - The para rubber tree is the most widely cultivated tree species for producing
      natural rubber (NR) latex. Unfortunately, rubber tree characteristics such as a
      long life cycle, heterozygous genetic backgrounds, and poorly understood genetic
      profiles are the obstacles to breeding new rubber tree varieties, such as those
      with improved NR yields. Recent evidence has revealed the potential importance of
      controlling microRNA (miRNA) decay in some aspects of NR regulation. To gain a
      better understanding of miRNAs and their relationship with rubber tree gene
      regulation networks, large genomic DNA insert-containing libraries were generated
      to complement the incomplete draft genome sequence and applied as a new powerful
      tool to predict a function of interested genes. Bacterial artificial chromosome
      and fosmid libraries, containing a total of 120,576 clones with an average insert
      size of 43.35 kb, provided approximately 2.42 haploid genome equivalents of
      coverage based on the estimated 2.15 gb rubber tree genome. Based on these
      library sequences, the precursors of 1 member of rubber tree-specific miRNAs and
      12 members of conserved miRNAs were successfully identified. A panel of miRNAs
      was characterized for phytohormone response by precisely identifying phytohormone
      responsive motifs in their promoter sequences. Furthermore, the quantitative real
      time PCR on ethylene stimulation of rubber trees was performed to demonstrate
      that the miR2118, miR159, miR164 and miR166 are responsive to ethylene, thus
      confirmed the prediction by genomic DNA analysis. The cis-regulatory elements
      identified in the promoter regions of these miRNA genes help augment our
      understanding of miRNA gene regulation and provide a foundation for further
      investigation of the regulation of rubber tree miRNAs. 

PMID- 24859133
TI  - A geneticist in the attic.

PMID- 24859134
TI  - Mission possible: getting to yes with Francois Jacob.

PMID- 24859136
TI  - Recollections of Francois Jacob.

PMID- 24859135
TI  - Viewing Francois Jacob (and Jacques Monod) through AGC & T.

PMID- 24859137
TI  - The continuity of bacterial and physicochemical evolution: theory and
      experiments.
AB  - The continuity of chemical and biological evolution, incorporating life's
      emergence, can be explored experimentally by energizing 'dead' bacterial
      biomacromolecules with nutrients under cycling physicochemical gradients. This
      approach arises from three evolutionary principles rooted in physical chemistry:
      (i) broken bacterial cells cannot spontaneously self-assemble into a living state
      without the supply of external energy - 2nd law of thermodynamics, (ii) the
      energy delivery must be cycling - the primary mechanism of chemical evolution at
      rotating planetary surfaces under solar irradiation, (iii) the cycling energy
      must act on chemical mixtures of high molecular diversity and crowding - provided
      by dead bacterial populations. 

PMID- 24859138
TI  - One day in Francois Jacob's laboratory.

PMID- 24859139
TI  - Memories of Francois Jacob: the inspirer and the friend.

PMID- 24859140
TI  - The Institut Pasteur attic dwellers: their origins, their paths to discovery.
AB  - Although this volume is dedicated to honoring Francois Jacob, I would like my
      contribution to broaden the context by recalling the background within which the
      scientists of those times operated. The specific scientific accomplishments of
      Jacob will certainly be covered by the other contributors who collaborated with
      him. My handful of recollections presented here largely as vignettes is intended
      to give the reader a feeling for the elements, many social, that shaped the
      generation of scientists that included such central figures, Jacob, Lwoff, Monod.
      It is the tale of a generation trying to express its creativity in a world caught
      up in war, irrational values and unforgivable inhumanity. Even this limited
      account is a great story bringing us important lessons for thought. 

PMID- 24859141
TI  - With Francois Jacob, from temperature sensitive mutants of Escherichia coli to
      mouse development and diseases.

PMID- 24859142
TI  - Through postdoc eyes.

PMID- 24859143
TI  - Le "grand" Francois.

PMID- 24859145
TI  - Francois Jacob, a high idea of "SCIENCE".

PMID- 24859144
TI  - Identification and characterization of a cis antisense RNA of the parC gene
      encoding DNA topoisomerase IV of Salmonella enterica serovar Typhi.
AB  - Bacterial cis-encoded antisense RNAs are transcribed from the opposite strand of
      protein coding genes, and their regulatory roles adapt cells to changing
      environmental conditions. By deep sequencing of the transcriptome of Salmonella
      enterica serovar Typhi, an antisense RNA that is encoded in cis to the parC gene
      was found. parC encodes the subunit A component of topoisomerase IV, a class of
      enzymes that relax both positively and negatively supercoiled DNA and are also
      required for segregation of daughter chromosomes in bacteria. Transcription of
      the 871 nucleotide antisense RNA was confirmed by northern blot and RACE analysis
      to be expressed mostly in the stationary phase of bacterial growth and also
      upregulated in iron limitation and osmotic stress conditions. Overexpression of
      the antisense RNA resulted in a significant increase in parC mRNA levels. Further
      analysis revealed that expression of the antisense RNA stabilizes the target
      mRNA, probably by protecting it from endoribonucleases. Our findings confirm and
      add to the ever increasing knowledge of the important role that regulatory
      antisense RNAs play in bacteria. 

PMID- 24859146
TI  - Souvenirs.

PMID- 24859147
TI  - DNA methyl transferase (DNMT) gene polymorphisms could be a primary event in
      epigenetic susceptibility to schizophrenia.
AB  - DNA methylation has been implicated in the etiopathology of various complex
      disorders. DNA methyltransferases are involved in maintaining and establishing
      new methylation patterns. The aim of the present study was to investigate the
      inherent genetic variations within DNA methyltransferase genes in predisposing to
      susceptibility to schizophrenia. We screened for polymorphisms in DNA
      methyltransferases, DNMT1, DNMT3A, DNMT3B and DNMT3L in 330 schizophrenia
      patients and 302 healthy controls for association with Schizophrenia in south
      Indian population. These polymorphisms were also tested for subgroup analysis
      with patient's gender, age of onset and family history. DNMT1 rs2114724 (genotype
      P = .004, allele P = 0.022) and rs2228611 (genotype P = 0.004, allele P = 0.022)
      were found to be significantly associated at genotypic and allelic level with
      Schizophrenia in South Indian population. DNMT3B rs2424932 genotype (P = 0.023)
      and allele (P = 0.0063) increased the risk of developing schizophrenia in males
      but not in females. DNMT3B rs1569686 (genotype P = 0.027, allele P = 0.033) was
      found to be associated with early onset of schizophrenia and also with family
      history and early onset (genotype P = 0.009). DNMT3L rs2070565 (genotype P =
      0.007, allele P = 0.0026) confers an increased risk of developing schizophrenia
      at an early age in individuals with family history. In-silico prediction
      indicated functional relevance of these SNPs in regulating the gene. These
      observations might be crucial in addressing and understanding the genetic control
      of methylation level differences from ethnic viewpoint. Functional significance
      of genotype variations within the DNMTs indeed suggest that the genetic nature of
      methyltransferases should be considered while addressing epigenetic events
      mediated by methylation in Schizophrenia. 

PMID- 24859149
TI  - A combinatorial approach to the design of vaccines.
AB  - We present two new problems of combinatorial optimization and discuss their
      applications to the computational design of vaccines. In the shortest lambda
      superstring problem, given a family S1,...,S(k) of strings over a finite
      alphabet, a set Tau of "target" strings over that alphabet, and an integer
      lambda, the task is to find a string of minimum length containing, for each i, at
      least lambda target strings as substrings of S(i). In the shortest lambda-cover
      superstring problem, given a collection X1,...,X(n) of finite sets of strings
      over a finite alphabet and an integer lambda, the task is to find a string of
      minimum length containing, for each i, at least lambda elements of X(i) as
      substrings. The two problems are polynomially equivalent, and the shortest lambda
      cover superstring problem is a common generalization of two well known
      combinatorial optimization problems, the shortest common superstring problem and
      the set cover problem. We present two approaches to obtain exact or approximate
      solutions to the shortest lambda-superstring and lambda-cover superstring
      problems: one based on integer programming, and a hill-climbing algorithm. An
      application is given to the computational design of vaccines and the algorithms
      are applied to experimental data taken from patients infected by H5N1 and HIV-1.

PMID- 24859148
TI  - Role of lipid rafts and GM1 in the segregation and processing of prion protein.
AB  - The prion protein (PrPC) is highly expressed within the nervous system. Similar
      to other GPI-anchored proteins, PrPC is found in lipid rafts, membrane domains
      enriched in cholesterol and sphingolipids. PrPC raft association, together with
      raft lipid composition, appears essential for the conversion of PrPC into the
      scrapie isoform PrPSc, and the development of prion disease. Controversial
      findings were reported on the nature of PrPC-containing rafts, as well as on the
      distribution of PrPC between rafts and non-raft membranes. We investigated
      PrPC/ganglioside relationships and their influence on PrPC localization in a
      neuronal cellular model, cerebellar granule cells. Our findings argue that in
      these cells at least two PrPC conformations coexist: in lipid rafts PrPC is
      present in the native folding (alpha-helical), stabilized by chemico-physical
      condition, while it is mainly present in other membrane compartments in a PrPSc
      like conformation. We verified, by means of antibody reactivity and circular
      dichroism spectroscopy, that changes in lipid raft-ganglioside content alters
      PrPC conformation and interaction with lipid bilayers, without modifying PrPC
      distribution or cleavage. Our data provide new insights into the cellular
      mechanism of prion conversion and suggest that GM1-prion protein interaction at
      the cell surface could play a significant role in the mechanism predisposing to
      pathology. 

PMID- 24859150
TI  - Structural probing of off-target G protein-coupled receptor activities within a
      series of adenosine/adenine congeners.
AB  - We studied patterns of off-target receptor interactions, mostly at G protein
      coupled receptors (GPCRs) in the uM range, of nucleoside derivatives that are
      highly engineered for nM interaction with adenosine receptors (ARs). Because of
      the considerable interest of using AR ligands for treating diseases of the CNS,
      we used the Psychoactive Drug Screening Program (PDSP) for probing promiscuity of
      these adenosine/adenine congeners at 41 diverse receptors, channels and a
      transporter. The step-wise truncation of rigidified, trisubstituted (at N6, C2,
      and 5' positions) nucleosides revealed unanticipated interactions mainly with
      biogenic amine receptors, such as adrenergic receptors and serotonergic
      receptors, with affinities as high as 61 nM. The unmasking of consistent sets of
      structure activity relationship (SAR) at novel sites suggested similarities
      between receptor families in molecular recognition. Extensive molecular modeling
      of the GPCRs affected suggested binding modes of the ligands that supported the
      patterns of SAR at individual receptors. In some cases, the ligand docking mode
      closely resembled AR binding and in other cases the ligand assumed different
      orientations. The recognition patterns for different GPCRs were clustered
      according to which substituent groups were tolerated and explained in light of
      the complementarity with the receptor binding site. Thus, some likely off-target
      interactions, a concern for secondary drug effects, can be predicted for
      analogues of this set of substructures, aiding the design of additional
      structural analogues that either eliminate or accentuate certain off-target
      activities. Moreover, similar analyses could be performed for unrelated
      structural families for other GPCRs. 

PMID- 24859151
TI  - Modeling and determination of directionality of the kerf in epifluorescence sharp
      bone trauma analysis.
AB  - Characteristics of sharp bone trauma can be extremely useful to determine the
      origin of cut marks and to provide information regarding the context of death.
      Using human ribs and clavicle bones, this study analyzes the characteristics of
      bone kerfs made by different bladed implements, thanks to epifluorescence
      macroscopy. This technique, which is a nondestructive tool that uses
      autofluorescence of bones, documents bone damage precisely with high resolution.
      Both qualitative and quantitative criteria are analyzed. Our results identify
      unique class characteristics on bone lesions, allowing modeling kerf depending on
      the weapon, regardless of the type of bone that is wounded. Moreover, we
      demonstrate for the first time microscopic criteria of directionality, using
      fluorescence excitation. Orientation of cracks, flakes, and lateral pushing back
      especially helps in determining the tip and the end of the lesion, leading to the
      position of the aggressor. Kerf wall characteristics and striation location are
      also very useful. Epifluorescence macroscopy could be a new tool of choice in
      anthropology through cut mark analysis in establishing how the blade was used and
      providing details about the blow. 

PMID- 24859152
TI  - Tanshinone IIA reduces the risk of Alzheimer's disease by inhibiting iNOS, MMP-2
      and NF-kappaBp65 transcription and translation in the temporal lobes of rat
      models of Alzheimer's disease.
AB  - Tanshinone IIA (Tan IIA), one of the major active constituents of the medicinal
      herb Salvia miltiorrhiza, has been reported to possess neuroprotective effects
      against the pathological features of Alzheimer's disease (AD), but the molecular
      mechanism underlying this effect remains unclear. To examine the effect of Tan
      IIA on AD, as well as the underlying molecular mechanisms, in vivo animal
      experiments and in vitro molecular biology investigations were employed in the
      present study. Firstly, a rat model of AD was successfully established by direct
      injection of the amyloid beta protein (Abeta) and then these rats were
      administered an interventional treatment of Tan IIA. The learning and memory
      ability of rats was evaluated in four groups (Control, Sham, AD and Tan IIA)
      utilizing a Morris water maze test. Quantitative (q)PCR was employed to detect
      the mRNA expression of inducible nitric oxide synthase (iNOS), matrix
      metalloproteinase-2 (MMP-2) and nuclear transcription factor kappa (NF-kappaBp65)
      in temporal lobe tissues and protein expression was determined with western blot
      analysis. In addition, association analyses between iNOS, MMP-2 and NF-kappaBp65
      at a transcriptional and translational level were performed utilizing Spearman's
      correlation analysis. In the present study, the results revealed that rats in the
      AD group demonstrated significant disruptions in learning and memory ability, and
      the symptoms were evidently reduced by Tan IIA. Furthermore, the upregulation of
      iNOS, MMP-2 and NF-kappaBp65 at a transcriptional and translational level in AD
      rats was distinctly inhibited by Tan IIA. Therefore, it was concluded that iNOS,
      MMP-2 and NF-kappaBp65 are involved in AD development, and Tan IIA may reduce AD
      risk by inhibiting transcription and translation of these genes. Furthermore, the
      positive correlation of iNOS and MMP-2 with NF-kappaBp65, respectively, provides
      evidence supporting the hypothesis that Tan IIA reduces AD risk by inhibiting
      iNOS and MMP-2 at a transcriptional and translational level through the NF-kappaB
      pathway. In summary, Tan IIA is an effective neuroprotective agent for AD
      therapy, and iNOS, MMP-2 and NF-kappaBp65 may be the potential molecular targets
      for manipulating this effect therapeutically. 

PMID- 24859153
TI  - [Frontal brain volume reduction due to antipsychotic drugs?].
AB  - This article reviews the results of longitudinal studies on frontal brain volume
      reduction in patients with schizophrenia spectrum disorders and focuses on the
      relationship with antipsychotic treatment. Based on a systematic literature
      search all studies were included in which results on changes of brain volumes
      over a longer period of time were correlated with antipsychotic treatment dose
      and disease severity. The findings indicate that there is evidence for grey and
      white matter volume changes of the frontal brain, which cannot be explained by
      the severity of the disease alone but are also very likely a manifestation of
      long-term effects of antipsychotics. Whether second generation antipsychotics
      have an advantage compared to first generation antipsychotics is currently
      unclear. Considering the contribution of antipsychotics to the changes in brain
      structure, which seem to depend on cumulative dosage and can exert adverse
      effects on neurocognition, negative and positive symptoms and psychosocial
      functioning, the guidelines for antipsychotic long-term drug treatment should be
      reconsidered. This is the reason why we and others recommend prescribing the
      lowest dose necessary to control symptoms. In non-schizophrenic psychiatric
      disorders, antipsychotics should be used only with great caution after a careful
      risk-benefit assessment. Moreover, treatment approaches which can help to
      minimize antipsychotic medication or even administer them only selectively are of
      increasing importance. 

PMID- 24859154
TI  - Transfer learning based clinical concept extraction on data from multiple
      sources.
AB  - Machine learning methods usually assume that training data and test data are
      drawn from the same distribution. However, this assumption often cannot be
      satisfied in the task of clinical concept extraction. The main aim of this paper
      was to use training data from one institution to build a concept extraction model
      for data from another institution with a different distribution. An instance
      based transfer learning method, TrAdaBoost, was applied in this work. To prevent
      the occurrence of a negative transfer phenomenon with TrAdaBoost, we integrated
      it with Bagging, which provides a "softer" weights update mechanism with only a
      tiny amount of training data from the target domain. Two data sets named BETH and
      PARTNERS from the 2010 i2b2/VA challenge as well as BETHBIO, a data set we
      constructed ourselves, were employed to show the effectiveness of our work's
      transfer ability. Our method outperforms the baseline model by 2.3% and 4.4% when
      the baseline model is trained by training data that are combined from the source
      domain and the target domain in two experiments of BETH vs. PARTNERS and BETHBIO
      vs. PARTNERS, respectively. Additionally, confidence intervals for the
      performance metrics suggest that our method's results have statistical
      significance. Moreover, we explore the applicability of our method for further
      experiments. With our method, only a tiny amount of labeled data from the target
      domain is required to build a concept extraction model that produces better
      performance. 

PMID- 24859155
TI  - Evaluating the effects of machine pre-annotation and an interactive annotation
      interface on manual de-identification of clinical text.
AB  - The Health Insurance Portability and Accountability Act (HIPAA) Safe Harbor
      method requires removal of 18 types of protected health information (PHI) from
      clinical documents to be considered "de-identified" prior to use for research
      purposes. Human review of PHI elements from a large corpus of clinical documents
      can be tedious and error-prone. Indeed, multiple annotators may be required to
      consistently redact information that represents each PHI class. Automated de
      identification has the potential to improve annotation quality and reduce
      annotation time. For instance, using machine-assisted annotation by combining de
      identification system outputs used as pre-annotations and an interactive
      annotation interface to provide annotators with PHI annotations for "curation"
      rather than manual annotation from "scratch" on raw clinical documents. In order
      to assess whether machine-assisted annotation improves the reliability and
      accuracy of the reference standard quality and reduces annotation effort, we
      conducted an annotation experiment. In this annotation study, we assessed the
      generalizability of the VA Consortium for Healthcare Informatics Research (CHIR)
      annotation schema and guidelines applied to a corpus of publicly available
      clinical documents called MTSamples. Specifically, our goals were to (1)
      characterize a heterogeneous corpus of clinical documents manually annotated for
      risk-ranked PHI and other annotation types (clinical eponyms and person
      relations), (2) evaluate how well annotators apply the CHIR schema to the
      heterogeneous corpus, (3) compare whether machine-assisted annotation
      (experiment) improves annotation quality and reduces annotation time compared to
      manual annotation (control), and (4) assess the change in quality of reference
      standard coverage with each added annotator's annotations. 

PMID- 24859156
TI  - Cryoprotective therapy for hepatocellular carcinoma: study of 51 patients with a
      single lesion.
AB  - Percutaneous cryoablation is a potentially curative treatment for hepatocellular
      carcinoma (HCC). After liver cryosurgery, rapid elevations of transaminases and
      bilirubin are common, but are usually transient and normalize within a few days.
      This study retrospectively reviewed clinical data from 51 patients who underwent
      liver cryoablation in our hospital during the past 4.5 years. Sixty-six
      percutaneous cryoablations were performed in these patients and transaminase and
      bilirubin levels before and after the procedure were observed. Although most
      patients received liver-protective treatment before cryosurgery, transaminase
      levels were double (mean alanine transaminase (ALT) and aspartate transaminase
      (AST) were 71 U/L and 85 U/L, respectively) the normal ranges in our hospital.
      One day after cryosurgery, ALT and AST had increased 3.3-fold (peak mean was 241
      U/L) and 5-fold (peak mean was 427 U/L), respectively, but were close to the
      preoperative level 5 days post-cryosurgery. No significant increase of serum
      bilirubin was observed. Serum transaminase and bilirubin levels were compared
      between hepatitis B positive and hepatitis B negative patients. Only in the
      hepatitis B positive group were total bilirubin (74 MUmol/L/23 MUmol/L=3.2) and
      direct bilirubin (45 MUmol/L/12 MUmol/L=3.8) more than 3 times the preoperative
      level 7-9 days after treatment. Overall, ALT and AST are valuable as indicators
      of liver function impairment following cryosurgery. In patients with hepatitis B
      virus, serum bilirubin was 3 times the preoperative level 7-9 days after
      cryosurgery. Liver-protective treatment may alleviate liver function impairment
      due to cryosurgery.

PMID- 24859157
TI  - Combined therapy of percutaneous cryoablation and traditional Chinese medicine
      can be a promising strategy for elderly or advanced lung cancer patients based on
      a retrospective clinical study.
AB  - Presently, elderly and advanced lung cancer patients have very limited treatment
      options. With no promising therapy, treatment of these patients is challenging.
      We have reviewed 119 primary lung cancer patients who received a combined
      percutaneous cryoablation and traditional Chinese medicine therapy (Cryo-TCM
      therapy) between 2005 and 2013. Out of 119 patients, 84.1% patients were elderly
      or advanced lung cancer when receiving cryoablation. Overall Survival time from
      the time of Diagnosis (DOS) and Cryoablation (COS) was 19 and 10 months
      respectively, which were longer than data previously published. Patients who
      accepted only Cryo-TCM therapy got similar DOS as those who were treated with
      Cryo-TCM and other classic anticancer therapies. Thus, Cryo-TCM therapy can
      prolong the survival time and can be used as the main therapy for the elderly or
      advanced lung cancer patients in China both in quality of life and cost
      effectiveness.

PMID- 24859158
TI  - Reporter assay for endo/lysosomal escape of toxin-based therapeutics.
AB  - Protein-based therapeutics with cytosolic targets are capable of exhibiting their
      therapeutic effect once they have escaped from the endosomes or lysosomes. In
      this study, the reporters-horseradish peroxidase (HRP), Alexa Fluor 488 (Alexa)
      and ricin A-chain (RTA)-were investigated for their capacity to monitor the
      endo/lysosomal escape of the ribosome-inactivating protein, saporin. The
      conjugates-saporin-HRP, (Alexa)saporin and saporin-KQ-RTA-were constructed, and
      the endo/lysosomal escape of these conjugates alone (lack of endo/lysosomal
      release) or in combination with certain structurally-specific triterpenoidal
      saponins (efficient endo/lysosomal escape) was characterized. HRP failed in
      reporting the endo/lysosomal escape of saporin. Contrastingly, Alexa Fluor 488
      successfully allowed the report of the process at a toxin concentration of 1000
      nM. In addition, single endo/lysosome analysis facilitated the determination of
      the amount of (Alexa)saporin released from each vesicle. RTA was also successful
      in reporting the endo/lysosomal escape of the enzymatically inactive mutant,
      saporin-KQ, but in this case, the sensitivity of the method reached a toxin
      concentration of 10 nM. In conclusion, the simultaneous usage of Alexa Fluor 488
      and RTA as reporters may provide the possibility of monitoring the endo/lysosomal
      escape of protein-based therapeutics in the concentration range of 10-1000 nM.

PMID- 24859159
TI  - Genetic divergence and signatures of natural selection in marginal populations of
      a keystone, long-lived conifer, Eastern White Pine (Pinus strobus) from Northern
      Ontario.
AB  - Marginal populations are expected to provide the frontiers for adaptation,
      evolution and range shifts of plant species under the anticipated climate change
      conditions. Marginal populations are predicted to show genetic divergence from
      central populations due to their isolation, and divergent natural selection and
      genetic drift operating therein. Marginal populations are also expected to have
      lower genetic diversity and effective population size (Ne) and higher genetic
      differentiation than central populations. We tested these hypotheses using
      eastern white pine (Pinus strobus) as a model for keystone, long-lived widely
      distributed plants. All 614 eastern white pine trees, in a complete census of two
      populations each of marginal old-growth, central old-growth, and central second
      growth, were genotyped at 11 microsatellite loci. The central populations had
      significantly higher allelic and genotypic diversity, latent genetic potential
      (LGP) and Ne than the marginal populations. However, heterozygosity and fixation
      index were similar between them. The marginal populations were genetically
      diverged from the central populations. Model testing suggested predominant north
      to south gene flow in the study area with curtailed gene flow to northern
      marginal populations. Signatures of natural selection were detected at three loci
      in the marginal populations; two showing divergent selection with directional
      change in allele frequencies, and one balancing selection. Contrary to the
      general belief, no significant differences were observed in genetic diversity,
      differentiation, LGP, and Ne between old-growth and second-growth populations.
      Our study provides information on the dynamics of migration, genetic drift and
      selection in central versus marginal populations of a keystone long-lived plant
      species and has broad evolutionary, conservation and adaptation significance. 

PMID- 24859160
TI  - Ethical behaviour in clinical practice: a multidimensional Rasch analysis from a
      survey of primary health care professionals of Barcelona (Catalonia, Spain).
AB  - PURPOSE: Normative ethics includes ethical behaviour health care professionals
      should uphold in daily practice. This study assessed the degree to which primary
      health care (PHC) professionals endorse a set of ethical standards from these
      norms. METHODS: Health care professionals from an urban area participated in a
      cross-sectional study. Data were collected using an anonymous, self-administered
      questionnaire. We examined the level of ethical endorsement of the items and the
      ethical performance of health care professionals using a Rasch multidimensional
      model. We analysed differences in ethical performance between groups according to
      sex, profession and knowledge of ethical norms. RESULTS: A total of 452
      Professionals from 56 PHC centres participated. The level of ethical performance
      was lower in items related to patient autonomy and respecting patient choices.
      The item estimate across all dimensions showed that professionals found it most
      difficult to endorse avoiding interruptions when seeing patients. We found
      significant differences in two groups: nurses had greater ethical performance
      than family physicians (p < 0.05), and professionals who reported having
      effective knowledge of ethical norms had a higher level of ethical performance (p
      < 0.01). CONCLUSIONS: Paternalistic behaviour persists in PHC. Lesser endorsement
      of items suggests that patient-centred care and patient autonomy are not fully
      considered by professionals. Ethical sensitivity could improve if patients are
      cared for by multidisciplinary teams.

PMID- 24859161
TI  - Down-regulation of microRNA-494 via loss of SMAD4 increases FOXM1 and beta
      catenin signaling in pancreatic ductal adenocarcinoma cells.
AB  - BACKGROUND & AIMS: Dysregulation of beta-catenin and the transcriptional
      activator FOXM1 mediate oncogenesis, but it is not clear how these proteins
      become dysregulated in tumors that do not typically carry mutations in
      adenomatous polyposis coli (APC) or beta-catenin, such as pancreatic ductal
      adenocarcinomas (PDACs). We searched for microRNAs that regulate levels of FOXM1
      in PDAC cells and samples from patients. METHODS: We identified microRNAs that
      affect levels of FOXM1 in PDACs using bioinformatic, genetic, and pharmacologic
      approaches. We altered expression of the microRNA-494 (miR-494) in PDAC cell
      lines (AsPC-1 and PANC-1) and examined the effects on FOXM1 and beta-catenin
      signaling and cell proliferation and colony formation. The cells were injected
      into immunocompromised mice and growth of xenograft tumors and liver metastases
      were measured. We performed immunohistochemical analyses of 10 paired PDAC and
      nontumor pancreatic tissue samples collected from untreated patients during
      surgery. RESULTS: We identified miR-494 as a negative regulator of FOXM1 levels
      in PDAC cells, and found that levels of this microRNA were reduced in PDAC
      specimens, compared with nontumor tissues. Loss of response of PDAC cells to
      transforming growth factor beta, owing to SMAD4 deficiency, reduced expression of
      miR-494. Transgenic expression of miR-494 in PDAC cells produced the same effects
      as reducing expression of FOXM1 or blocking nuclear translocation of beta
      catenin, reducing cell proliferation, migration, and invasion, and increasing
      their sensitivity to gemcitabine. Reduced expression of miR-494 correlated with
      PDAC metastasis and reduced survival times of patients. CONCLUSIONS: Loss of
      SMAD4 in PDAC cells leads to reduced levels of miR-494, increased levels of
      FOXM1, and nuclear localization of beta-catenin. miR-494 might be developed as a
      prognostic marker for patients with PDAC or a therapeutic target.

PMID- 24859162
TI  - Indian Hedgehog mediates gastrin-induced proliferation in stomach of adult mice.
AB  - BACKGROUND & AIMS: Loss of expression of Sonic Hedgehog (Shh) from parietal cells
      results in hypergastrinemia in mice, accompanied by increased expression of
      Indian Hedgehog (Ihh) and hyperproliferation of surface mucous cells. We
      investigated whether hypergastrinemia induces gastric epithelial proliferation by
      activating Ihh signaling in mice. METHODS: We studied mice with parietal cell
      specific deletion of Shh (PC-Shh(KO)) and hypergastrinemia, crossed with gastrin
      deficient (GKO) mice (PC-Shh(KO)/GKO). When mice were 3-4 months old, gastric
      tissues were collected and analyzed by histology, for incorporation of
      bromodeoxyuridine, and for expression of the surface mucous cell marker Ulex
      europaeus. PC-Shh(KO)/GKO mice were given gastrin infusions for 7 days; gastric
      surface epithelium was collected and expression of Ihh was quantified by laser
      capture microdissection followed by quantitative reverse transcriptase polymerase
      chain reaction. Mouse stomach-derived organoids were incubated with or without
      inhibitors of WNT (DKK1) or Smoothened (vismodegib) and then cocultured with
      immortalized stomach mesenchymal cells, to assess proliferative responses to
      gastrin. RESULTS: Gastric tissues from PC-Shh(KO)/GKO mice with hypergastrinemia
      had an expanded surface pit epithelium, indicated by a significant increase in
      numbers of bromodeoxyuridine- and Ulex europaeus-positive cells, but there was no
      evidence for hyperproliferation. Gastrin infusion of PC PC-Shh(KO)/GKO mice
      increased expression of Ihh and proliferation within the surface epithelium
      compared with mice given infusions of saline. In gastric organoids cocultured
      with immortalized stomach mesenchymal cells, antagonists of WNT and Smoothened
      inhibited gastrin-induced proliferation and WNT activity. Activity of WNT in
      media collected from immortalized stomach mesenchymal cells correlated with
      increased expression of glioma-associated oncogene homolog 1, and was inhibited
      by DKK1 or vismodegib. CONCLUSIONS: Ihh signaling mediates gastrin-induced
      proliferation of epithelial cells in stomachs of adult mice.

PMID- 24859166
TI  - Hybrid operation for combined aortic arch aneurysm and aortic root dilation in a
      Jehovah's witness patient.
AB  - Aortic surgery for Jehovah's Witness patients with extended aneurysms is
      challenging. The present report describes a case of a 65-year-old male Jehovah's
      Witness with aortic aneurysm that extended from the ascending to the transverse
      aortic arch. Two-stage hybrid operation was performed as follows: ascending
      aortic replacement with debranching of brachiocephalic artery, followed by extra
      anatomic bypass of cervical arteries, and thoracic aortic stent-grafting. The
      patient fully recovered without complication, and the lowest hemoglobin
      concentration during the hospital admission was 9.5 g/dL. We conclude that the
      hybrid procedure was effective in securing a margin of safety for bloodless
      aortic surgery. 

PMID- 24859164
TI  - Acute pancreatitis in patients with type 2 diabetes mellitus treated with
      dipeptidyl peptidase-4 inhibitors: a population-based nested case-control study.
AB  - BACKGROUND: Concern about an increasing risk of acute pancreatitis associated
      with incretin-based drugs, including dipeptidyl peptidase-4 (DPP-4) inhibitors
      and glucagon-like peptide-1 analogs, has emerged recently. OBJECTIVE: This nested
      case-control study examined the association between the use of DPP-4 inhibitors
      and acute pancreatitis using Taiwan's National Health Insurance Research
      Database. METHODS: From a study cohort of patients with type 2 diabetes mellitus,
      we identified 1,957 acute pancreatitis cases (patients who had been admitted with
      a diagnosis of acute pancreatitis) and 7,828 age-, sex-, and cohort entry year
      matched controls between 2000 and 2011. Multivariate conditional regression
      models were used to estimate the association between the use of DPP-4 inhibitors
      and acute pancreatitis. Sensitivity analyses were conducted by varying the
      definitions of timing of exposure to DPP-4 inhibitors. RESULTS: The risks of
      acute pancreatitis among current and past users of DPP-4 inhibitors were
      comparable with those of non-users (current users: adjusted odds ratio (aOR)
      1.04; 95% CI [0.89-1.21]; past users: aOR 1.61 [0.93-2.77]). Similar results were
      found in sensitivity analyses with various definitions of "current users" of DPP
      4 inhibitors. Nevertheless, the adjusted risk of acute pancreatitis was found to
      be increased significantly in patients with gallstone disease (aOR 5.89 [4.71
      7.35]), alcohol-related disease (aOR 5.36 [4.05-7.08]), hypertriglyceridemia (aOR
      1.80 [1.26-2.56]), pancreatic disease (aOR 17.29 [10.60-28.19]), and a higher
      Diabetes Complications Severity Index (DCSI) score (DCSI 3-4: aOR 1.49 [1.21
      1.84]; DCSI>=5: aOR 1.32 [1.01-1.73]). CONCLUSIONS: This population-based study
      extends previous evidence by exploring the potential association between DPP-4
      inhibitor use and the risk of acute pancreatitis in an ethnic Chinese type 2
      diabetic cohort. We found that underlying diseases and severity of diabetes but
      not DPP-4 inhibitor use were associated with acute pancreatitis.

PMID- 24859163
TI  - Are the safety profiles of antipsychotic drugs used in dementia the same? An
      updated review of observational studies.
AB  - With an increase in the global prevalence of dementia, there is also an increase
      in behavioural and psychological symptoms of dementia (BPSD) for which
      antipsychotic drugs are often used. Despite several safety warnings on
      antipsychotic use in dementia, there is little evidence to support the efficacy
      of antipsychotics in individual BPSD symptoms or to evaluate the drug safety
      profile by individual antipsychotic drug. There is emerging but scarce evidence
      that suggests an inter-drug variability between antipsychotic safety outcomes in
      BPSD. The objective of this review was to examine the existing literature on
      antipsychotic drug use in dementia patients; in particular to see whether inter
      drug differences regarding antipsychotic safety were reported. A literature
      search was conducted for observational studies published in the English language
      from 2004 to 2014 that reported the risk of all-cause mortality, cerebrovascular
      events, pneumonia and other outcomes such as hip/femur fracture, deep vein
      thrombosis (DVT) and hyperglycaemia. Six of 16 mortality studies (38%), 7 of 28
      stroke studies (25%), 1 of 6 pneumonia (17%) studies and 2 of 6 fracture studies
      (33%) investigated inter-drug safety outcomes in elderly patients/dementia
      patients, while to our knowledge, there are no studies investigating the inter
      drug variation of deep-vein thrombosis and hyperglycaemia risk. The results of
      the observational studies provide mixed results on the safety of antipsychotics
      in BPSD but it is clear that there are differences between the safety profiles of
      antipsychotic drugs. Robust evidence of such inter-drug variability could
      significantly improve patient safety as antipsychotics become more targeted to
      clinical risk factors.

PMID- 24859167
TI  - Improving the prognosis: developing the right tool for the right patients.

PMID- 24859168
TI  - Evaluation of left ventricular systolic strain in children with Kawasaki disease.
AB  - The current study aimed to assess left ventricular (LV) longitudinal systolic
      strains in children with KD using two-dimensional speckle-tracking imaging and to
      analyze the relationship of LV myocardial deformation to coronary lesions and
      laboratory markers. The study enrolled 101 children with acute KD. An additional
      50 age- and gender-matched normal children were enrolled as control subjects.
      During different phases of KD, echocardiograms were recorded for 61 children. Two
      dimensional strain analysis software was used to track myocardial movement and
      obtain the strain from each LV segment. The LV longitudinal systolic strain
      decreased significantly in children with acute KD but increased immediately after
      intravenous immunoglobulin therapy. At 6-8 weeks after the onset of KD, all LV
      strains had recovered to normal. The LV systolic strain was not associated with
      coronary dilation in either acute or convalescent KD. In acute KD, aspartate
      transaminase, alanine transaminase, erythrocyte sedimentation rate, C-reactive
      protein (CRP), and hemoglobin (Hb) were found to be associated with coronary
      dilation, whereas LV systolic strains were found to be correlated with elevated
      CRP and decreased Hb. Speckle-tracking imaging of LV systolic strain was simple
      and accurate in evaluating LV function during different phases of KD. No
      association between LV dysfunction and coronary dilation was observed, but a
      relationship with CRP and Hb was found. Further studies are recommended to
      validate the current study results and explore further how these findings can
      improve clinical practice.

PMID- 24859170
TI  - Abstracts of Papers Presented at the Fifty-Ninth Annual Meeting of the Health
      Physics Society, 13 July - 17 July, 2014, Baltimore, Maryland.

PMID- 24859169
TI  - Increased P-wave and QT dispersions necessitate long-term follow-up evaluation of
      Down syndrome patients with congenitally normal hearts.
AB  - Reports state that Down syndrome (DS) patients with congenitally normal hearts
      might experience the development of cardiac abnormalities such as cardiac
      autonomic dysfunction, valvular lesions, bradycardia, and atrioventricular block.
      However, the presence of any difference in terms of P-wave dispersion (PWd) and
      QT dispersion (QTd) was not evaluated previously. This study prospectively
      investigated 100 DS patients with structurally normal hearts and 100 age- and sex
      matched healthy control subjects. Standard 12-lead electrocardiograms were used
      to assess and compare P-wave and QT durations together with PWd and QTd. The
      median age of the DS patients and control subjects was 48 months. Heart rates and
      P-wave and QT dispersions were significantly greater in the DS group than in the
      control group (113 +/- 22.9 vs 98.8 +/- 16.6 bpm, p < 0.001; 31.3 +/- 9.5 vs 24
      +/- 8.6 ms, p < 0.001; and 46.6 +/- 15.9 vs 26 +/- 9.1 ms, p < 0.001,
      respectively). A positive correlation was found between PWd and age in the DS
      patients (p < 0.05; r = 0.2). All children with DS should be followed up
      carefully with electrocardiography in terms of increased P-wave and QT
      dispersions even in the absence of concomitant congenital heart disease for
      management of susceptibility to arryhthmias.

PMID- 24859171
TI  - Possible selection of viable human blastocysts after vitrification by monitoring
      morphological changes.
AB  - PURPOSE: Morphological assessment of human blastocysts has been effective for
      selecting embryos with high potential. However, they often show repeated
      shrinkage and expansion toward their hatching. Here we assessed whether capturing
      morphological changes over time of vitrified-warmed blastocysts could lead to a
      better selection of viable embryos from shrunken blastocysts. METHODS: The
      implantation rates of vitrified-warmed blastocysts that were shrunken or expanded
      (developing) at the time of loading for transfer were compared among 2,729 cycles
      that were subjected to single blastocyst transfer. Vitrified (107) and fresh
      blastocysts (17) were donated for the experimental study. To assess the
      relationship between morphology (expanded vs. shrunken) and the mitochondrial
      respiration of blastocysts, the oxygen consumption rate (OCR) was analyzed for 55
      specimens using an uncoupler of oxidative phosphorylation. The remaining 69
      blastocysts were used for recording morphological changes every 15 min for 48 h
      after warming. RESULTS: Because there were no surplus embryos, 7 % of the
      vitrified-warmed blastocysts were shrunken and transferred. The shrunken embryos
      had sufficient implantation ability (40 %). The OCR of the shrunken embryos was
      significantly lower than that of their expanded counterparts. Upon exposure to
      the uncoupler, the OCR of some shrunken embryos increased to levels similar to
      the expanded specimens. Time-lapse images revealed some shrunken embryos which
      formed blastocoel by 5 h following warming exhibited developmental competence to
      the hatched stage. CONCLUSIONS: Data of the present study suggest a group of
      shrunken blastocysts contains many viable and clinically available embryos and
      time-lapse observation of vitrified-warmed blastocysts is a potential method to
      distinguish viable embryos from shrunken blastocysts.

PMID- 24859172
TI  - The neurodevelopmental effects of serotonin: a behavioural perspective.
AB  - Serotonin is well known for its role in psychiatric disorders like depression and
      autism, but it is less clear how aberrant behaviour associated with these
      disorders are shaped by serotonergic alterations during prenatal and postnatal
      development. The use of serotonergic antidepressant agents and other drugs during
      pregnancy and breastfeeding can change brain development, and the behavioural
      consequences may depend on the stage of development; prenatal, early and late
      postnatal. The aim of this review is to provide an overview of the behavioural
      consequences of changes in serotonin levels during these three critical
      developmental stages. The studies together demonstrate that risk for mood
      disorders (including social deficits) is related to serotonergic perturbations
      during the prenatal and postnatal phases, whereas risk for autism-like features
      and sexual abnormalities increases when serotonin levels are increased during the
      postnatal period. This insight may inform timed strategies to reduce risk for
      psychiatric disorders. 

PMID- 24859173
TI  - Anatomical deficits in adult posttraumatic stress disorder: a meta-analysis of
      voxel-based morphometry studies.
AB  - Evidence from previous anatomical studies indicate that widespread brain regions
      are involved in the pathogenesis of posttraumatic stress disorder (PTSD). The aim
      of the present study was to quantitatively integrate the literature on structural
      abnormalities seen on individuals with PTSD. Twenty voxel-based analysis studies
      were analysed through a comprehensive series of meta-analyses. Compared with
      healthy controls, PTSD patients showed a significant reduction in grey matter
      (GM) in the left anterior cingulate gyrus (ACC) at the whole-brain level. Several
      brain regions, including the left ACC, the left insula and the right
      parahippocampal gyrus were significantly smaller in individuals with PTSD than in
      trauma-exposed healthy subjects. Furthermore, the clinician-administered PTSD
      scale scores were negatively correlated with GM in the left ACC and positively
      correlated with GM in the left insula. In addition, PTSD patients who experienced
      accidental or non-accidental trauma had anatomical changes in different brain
      regions. These results suggest that the smaller ACC and insular cortex within the
      limbic-prefrontal circuit contribute to the pathogenesis of PTSD. Moreover, the
      PTSD patients with different types of trauma may have different cerebral
      deficits. 

PMID- 24859174
TI  - Differences between the nonselective adenosine receptor antagonists caffeine and
      theophylline in motor and mood effects: studies using medium to high doses in
      animal models.
AB  - RATIONALE: Caffeine and theophylline are methylxanthines that are broadly
      consumed, sometimes at high doses, and act as minor psychostimulants. Both are
      nonselective adenosine antagonists for A1 and A2A receptors, which are
      colocalized with dopamine D1 and D2 receptors in striatal areas. Adenosine
      antagonists generally have opposite actions to those of dopamine antagonists.
      Although the effects of caffeine are widely known, theophylline has been much
      less well characterized, especially at high doses. METHODS: Adult male CD1 mice
      were used to study the effect of a broad range of doses (25.0, 50.0 or
      100.0mg/kg) of caffeine and theophylline on measures of spontaneous locomotion
      and coordination, as well as the pattern of c-Fos immunoreactivity in brain areas
      rich in adenosine and dopamine receptors. In addition, we evaluated possible
      anxiety and stress effects of these doses. RESULTS: Caffeine, at these doses,
      impaired or suppressed locomotion in several paradigms. However, theophylline was
      less potent than caffeine at suppressing motor parameters, and even stimulated
      locomotion. Both drugs induced corticosterone release, however caffeine was more
      efficacious at intermediate doses. While caffeine showed an anxiogenic profile at
      all doses, theophylline only did so at the highest dose used (50mg/kg). Only
      theophylline increased c-Fos immunoreactivity in cortical areas. CONCLUSION:
      Theophylline has fewer disruptive effects than caffeine on motor parameters and
      produces less stress and anxiety effects. These results are relevant for
      understanding the potential side effects of methylxanthines when consumed at high
      doses.

PMID- 24859175
TI  - The effects of cocaine and mazindol on the cognitive judgement bias of rats in
      the ambiguous-cue interpretation paradigm.
AB  - Recent research has shown that pharmacological enhancement of dopaminergic
      function increases an optimism bias in humans. The present study investigated
      whether acute dopaminergic system stimulation through the administration of two
      dopamine-mimetic drugs, cocaine and mazindol, have similar effects in rats. To
      accomplish this goal, after initial behavioural training, two groups of rats
      received single injections of either cocaine or mazindol and were subsequently
      tested with the ambiguous-cue interpretation (ACI) paradigm. Both drugs were
      administered in three doses using the fully randomised Latin square designs.
      Cocaine (1, 2 and 5mg/kg) had no significant effect on the interpretation of the
      ambiguous cue. Mazindol at all three doses (0.5, 1 and 2mg/kg) significantly
      biased animals towards negative interpretation of the ambiguous cue. The results
      are discussed in relation to pharmacological and behaviourally evoked actions of
      tested compounds. 

PMID- 24859176
TI  - Biomechanical analysis of distal femoral fracture fixation: dynamic condylar
      screw versus locked compression plate.
AB  - BACKGROUND: This human cadaveric study i ntroduces a laboratory model to
      establish and compare the fixation stability of the distal femoral locking plate
      (DFLP) and dynamic condylar screw (DCS) in distal femoral fracture fixation.
      MATERIALS AND METHODS: The study was conducted on 16 fresh cadaveric femoral
      specimens, 8 implanted with the DCS and the other 8 with the DFLP. The construct
      was made unstable by removing a standard-sized medial wedge with a 1-cm base (gap
      osteotomy) beginning 6 cm proximal to the lateral joint line in the distal
      metaphyseal region with loss of the medial buttress. Each specimen underwent
      axial and torsional stiffness testing along with cyclic axial loading to failure.
      The mean DEXA value for the DFLP group was 0.82 g/cm(2) and in the DCS group was
      0.79 g/cm(2). RESULTS: Axial stiffness in the DFLP group was significantly higher
      than in the DCS group, but no significant difference was found in torsional
      stiffness between the groups. A significant difference was found in the load-to
      failure results between the groups. Plastic and total deformation was
      significantly higher in constructs in the DCS group than in those in the DFLP
      group. Total energy absorbed before construct failure was also significantly
      higher in the DFLP group than in the DCS group. CONCLUSIONS: The DFLP construct
      proved stronger than the DCS in both axial stiffness and cyclic loading, but
      similar in torsional stiffness in biomechanical testing in a simulated A3 distal
      femoral fracture.

PMID- 24859177
TI  - Significant increase of plasma tetranectin in ovx mice as defined by proteomics
      analysis.
AB  - BACKGROUND: Proteomics is recognized as a useful tool in the dynamic screening of
      plasma protein expression. This study aimed to identify increased expressions of
      novel plasma proteins in ovariectomized mice (ovx) using selective reaction
      monitoring (SRM) validation in combination with electrospray ionized-quadrupole
      time-of-flight mass spectrometry (ESI-Q-TOF-MS) screening. MATERIALS AND METHODS:
      Twenty-week-old female C57BL/6 mice were ovariectomized or subjected to surgical
      exposure of the ovaries alone (sham). Blood plasma protein at 4 weeks after these
      operations was pooled for the ovx and sham group each and separated on SDS-PAGE,
      and then digested by peptides, which were first differentially displayed by ESI-Q
      TOF-MS analysis. Mass spectra of peptides upregulated more than twofold in ovx
      compared to sham mice were selected for protein identification by ESI-Q-TOF-MS.
      The selected peptides were further validated in independent samples by SRM using
      electrospray ionized-triple quadrupole-linear ion trap mass spectrometry (ESI
      QqLIT-MS). Optimum transitions for SRM were manually chosen for their high
      specificity in identifying peptides derived from the candidate proteins. RESULTS:
      Differential analysis of peptides revealed 1,108 upregulated peptides in ovx
      compared with sham control mice. Among the upregulated peptides, 231 nonredundant
      proteins were identified. Validation analysis for the potential use of these
      proteins as markers of bone turnover was performed using ESI-QqLIT-MS. The four
      proteins from the plasma samples, namely mannose-binding lectin-C, major urinary
      protein 2, type I collagen alpha 2 chain, and tetranectin, were evaluated in a
      blinded manner. A statistically significant elevation of all four proteins in the
      plasma of ovx mice was confirmed by SRM. Of the four upregulated plasma proteins,
      tetranectin increased by almost 50 times in the ovx mice compared with the sham
      mice. CONCLUSIONS: On the basis of proteomics analysis, this study demonstrated
      that four plasma proteins were significantly elevated in the ovx mice; of these,
      tetranectin was markedly upregulated by almost 50 times compared with the sham
      mice.

PMID- 24859178
TI  - Diprenylated Indole Alkaloids from Fruits of Hexalobus monopetalus.
AB  - New hexalobine type alkaloid, 5-(2",3"-epoxy-3"-methylbutyl)-3-(3'-hydroxy-3'
      methyl-1'-acetyloxy-but-2'-yl)indole (1) alongside the known hexalobines 3-(2',3'
      dihydroxy-3'-methylbutyl)-5-(3"-methylcrotonoyl) indole (2), 3,5-hexalobine C (3)
      and 3,5-hexalobine D (4) were isolated from fruits of Hexalobus monopetalus.
      Compounds 3 and 4 exhibited antifungal activity against Candida albicans. 

PMID- 24859179
TI  - Alternative downstream processes for production of antibodies and antibody
      fragments.
AB  - Protein-A or Protein-L affinity chromatography and virus inactivation are key
      processes for the manufacturing of therapeutic antibodies and antibody fragments.
      These two processes often involve exposure of therapeutic proteins to denaturing
      low pH conditions. Antibodies have been shown to undergo conformational changes
      at low pH, which can lead to irreversible damages on the final product. Here, we
      review alternative downstream approaches that can reduce the degree of low pH
      exposure and consequently damaged product. We and others have been developing
      technologies that minimize or eliminate such low pH processes. We here cover
      facilitated elution of antibodies using arginine in Protein-A and Protein-G
      affinity chromatography, a more positively charged amidated Protein-A, two
      Protein-A mimetics (MEP and Mabsorbent), mixed-mode and steric exclusion
      chromatography, and finally enhanced virus inactivation by solvents containing
      arginine. This article is part of a Special Issue entitled: Recent advances in
      molecular engineering of antibody.

PMID- 24859180
TI  - Editorial in response to the systematic review by de Vos et al: 'Strong evidence
      against platelet-rich plasma injections for chronic lateral epicondylar
      tendinopathy: a systematic review'.

PMID- 24859181
TI  - 2014 consensus statement from the first Economics of Physical Inactivity
      Consensus (EPIC) conference (Vancouver).
AB  - This article describes major topics discussed from the 'Economics of Physical
      Inactivity Consensus Workshop' (EPIC), held in Vancouver, Canada, in April 2011.
      Specifically, we (1) detail existing evidence on effective physical inactivity
      prevention strategies; (2) introduce economic evaluation and its role in health
      policy decisions; (3) discuss key challenges in establishing and building health
      economic evaluation evidence (including accurate and reliable costs and clinical
      outcome measurement) and (4) provide insight into interpretation of economic
      evaluations in this critically important field. We found that most methodological
      challenges are related to (1) accurately and objectively valuing outcomes; (2)
      determining meaningful clinically important differences in objective measures of
      physical inactivity; (3) estimating investment and disinvestment costs and (4)
      addressing barriers to implementation. We propose that guidelines specific for
      economic evaluations of physical inactivity intervention studies are developed to
      ensure that related costs and effects are robustly, consistently and accurately
      measured. This will also facilitate comparisons among future economic evidence.

PMID- 24859184
TI  - Analysis of results of recurrence and progression rates of high-grade Ta bladder
      cancer and comparison with results of high-grade T1.
AB  - INTRODUCTION: We aimed to evaluate the long-term recurrence and progression rates
      in a Turkish population with high-grade Ta and T1 bladder cancer and to determine
      malign potential of high-grade Ta bladder cancer. METHODS: 191 patients who had
      non-invasive bladder cancer were evaluated at a single institution between 2005
      and 2010. Median follow-up was 55.6 months (13-108). Long-term follow-up results
      of recurrence and progression rates of high-grade Ta and T1 were analyzed and
      compared with each other. RESULTS: Of the 191 patients, 143 (74.9%) were high
      grade T1 and 48 (25.1%) were high-grade Ta. Of the 143 patients who were high
      grade T1, 39 (27.2%) responded to the induction BCG without recurrence. 33 (23%)
      patients had invasion deep into the muscle layer. 61 (42%) patients had recurred
      as high-grade T1. Of the 48 patients who were high-grade Ta, 15 (31%) responded
      to induction BCG without recurrence. 18 (37.5%) patients had recurrence as high
      grade Ta. 12 (25%) patients had invasion deep into to the muscle layer. Of all
      the patients, 13 (7%) patients died of causes related to bladder cancer. In a
      multivariate analysis, concomitant CIS was statistically significant for the
      progression of high-grade Ta bladder cancer (p<0.005). CONCLUSIONS: According to
      the data of the current study, the presence of concomitant CIS in patients with
      high-grade bladder cancers is associated with a higher risk of progression. There
      is a need for larger scale multi-institutional studies in order to support the
      hypothesis that high-grade Ta tumors should be considered as T1 tumors.

PMID- 24859185
TI  - alpha-Linolenic acid: nutraceutical, pharmacological and toxicological
      evaluation.
AB  - alpha-Linolenic acid (ALA), a carboxylic acid with 18 carbons and three cis
      double bonds, is an essential fatty acid needed for human health and can be
      acquired via regular dietary intake of foods that contain ALA or dietary
      supplementation of foods high in ALA, for example flaxseed. ALA has been reported
      to have cardiovascular-protective, anti-cancer, neuro-protective, anti
      osteoporotic, anti-inflammatory, and antioxidative effects. ALA is the precursor
      of longer chain omega-3 fatty acids, eicosapentaenoic acid (EPA) and
      docosahexaenoic acid (DHA), but its beneficial effects on risk factors for
      cardiovascular diseases are still inconclusive. The recommended intake of ALA for
      cardiovascular health is reported to be 1.1-2.2g/day. Although there are limited
      toxicological data for ALA, no serious adverse effects have been reported. The
      evidence on an increased prostate cancer risk in association with dietary ALA is
      not conclusive. Based on the limited data currently available, it may be
      concluded that ALA may be beneficial as a nutraceutical/pharmaceutical candidate
      and is safe for use as a food ingredient. 

PMID- 24859186
TI  - Chronic exposure to simulated space conditions predominantly affects cytoskeleton
      remodeling and oxidative stress response in mouse fetal fibroblasts.
AB  - Microgravity and cosmic rays as found in space are difficult to recreate on
      earth. However, ground-based models exist to simulate space flight experiments.
      In the present study, an experimental model was utilized to monitor gene
      expression changes in fetal skin fibroblasts of murine origin. Cells were
      continuously subjected for 65 h to a low dose (55 mSv) of ionizing radiation
      (IR), comprising a mixture of high-linear energy transfer (LET) neutrons and low
      LET gamma-rays, and/or simulated microgravity using the random positioning
      machine (RPM), after which microarrays were performed. The data were analyzed
      both by gene set enrichment analysis (GSEA) and single gene analysis (SGA).
      Simulated microgravity affected fetal murine fibroblasts by inducing oxidative
      stress responsive genes. Three of these genes are targets of the nuclear factor
      erythroid 2 p45-related factor 2 (Nrf2), which may play a role in the cell
      response to simulated microgravity. In addition, simulated gravity decreased the
      expression of genes involved in cytoskeleton remodeling, which may have been
      caused by the downregulation of the serum response factor (SRF), possibly through
      the Rho signaling pathway. Similarly, chronic exposure to low-dose IR caused the
      downregulation of genes involved in cytoskeleton remodeling, as well as in cell
      cycle regulation and DNA damage response pathways. Many of the genes or gene sets
      that were altered in the individual treatments (RPM or IR) were not altered in
      the combined treatment (RPM and IR), indicating a complex interaction between RPM
      and IR.

PMID- 24859187
TI  - Effect of egg washing and correlation between cuticle and egg penetration by
      various Salmonella strains.
AB  - In Australia, Europe and the United States, eggs and egg products are frequently
      associated with Salmonella food poisoning outbreaks. Many of the egg-associated
      Salmonella outbreaks have been due to the products such as mayonnaise, ice-cream
      and cold desserts which are eaten without cooking following the addition of raw
      egg. The ability of four Salmonella isolates (one each of S. Singapore, S.
      Adelaide, S. Worthington and S. Livingstone) to penetrate washed and unwashed
      eggs using whole egg and agar egg penetration methods was investigated in the
      current study. The results of the agar penetration experiment indicated that all
      the isolates used in the present study have the capacity to penetrate the
      eggshell. Eggshell penetration by the S. Worthington isolate was higher but not
      significant (p=0.06) in washed eggs compared to unwashed eggs. However, for all
      other isolates (S. Singapore, S. Adelaide and S. Livingstone), there was no
      significant difference in penetration of washed and unwashed eggs. Statistical
      analysis indicated that cuticle score was a significant linear predictor of
      Salmonella eggshell penetration. Whole egg penetration results showed that all of
      the Salmonella isolates used in the present study were capable of surviving on
      the eggshell surface after 21days of incubation (at 20 degrees C) following a
      high dose of inoculation (10(5)CFU/mL). The combined data of all isolates
      demonstrated that, the survival rate of Salmonella on eggshells (inoculated with
      10(5)CFU/mL) was significantly higher (p=0.002) at 20 degrees C as compared to 37
      degrees C. S. Singapore, S. Worthington, and S. Livingstone were not detected in
      egg internal contents whereas S. Adelaide was detected in one egg's internal
      contents. 

PMID- 24859188
TI  - The influence of fat and monoacylglycerols on growth of spore-forming bacteria in
      processed cheese.
AB  - Highly undesirable microbial contaminants of processed cheese are endospore
      forming bacteria of the genera Bacillus and Clostridium. Survival of Bacillus
      subtilis, B. cereus, Clostridium butyricum and C. sporogenes was examined in
      model processed cheese samples supplemented with monoacylglycerols. In processed
      cheese samples, monoacylglycerols of undecanoic, undecenoic, lauric and
      adamantane-1-carboxylic acid at concentration of 0.15% w/w prevented the growth
      and multiplication of both Bacillus species throughout the storage period. The
      two species of Clostridium were less affected by monoacylglycerols in processed
      cheese samples and only partial inhibition was observed. The effect of milk fat
      content on microbial survival in processed cheese was also evaluated. The growth
      of Bacillus sp. was affected by the fat level of processed cheese while
      population levels of Clostridium sp. did not differ in processed cheese samples
      with 30, 40 and 50% fat in dry matter. 

PMID- 24859189
TI  - Assessment of high and low enterotoxin A producing Staphylococcus aureus strains
      on pork sausage.
AB  - Three Staphylococcus aureus strains representing different alleles of the
      Siphoviridae prophage-encoded enterotoxin A (SEA) gene, including two high-SEA
      producing strains and one low-SEA-producing strain were studied to investigate
      sea expression and SEA formation on a frankfurter type of sausage. The effect of
      lactic acid, an antimicrobial compound used as a preservative in food, was also
      investigated on the same product. All three strains were grown on pork sausages
      at 15 degrees C for 14days in the presence or absence of lactic acid (1 or 2%
      v/v). Growth, sea mRNA expression and SEA formation were regularly monitored and
      compared between non-treated and treated sausages. For all experiments performed,
      the extracellular SEA formation significantly differed between the high- and low
      SEA-producing strains, although growth and viability were overall the same. For
      the low producer (Sa51), the accumulated amount of extracellular SEA formed after
      14days was close to the detection limit (less than 1ng/g) in all conditions;
      while Sa21 and Sa17, the two high-producing strains, formed 250+/-25.37ng/g and
      750+/-82.65ng/g in non-treated sausage and 150+/-75.75ng/g and 300+/-83.89ng/g
      when treated with 1% lactic acid, respectively, after 14days. Sausages treated
      with 2% lactic acid followed the same pattern as above, but with an extended lag
      phase to 4days and reduced levels of enterotoxin formed for all strains. The
      difference in the level of SEA between the two high-producing strains is most
      likely due to the different clonal lineages of the sea-encoded Siphoviridae
      phages where induction of the prophage potentially could be the reason for higher
      production of SEA in one of the lines. Furthermore, a prolonged expression of sea
      gene in the two high-producing strains was observed during the entire incubation
      period, while the sea expression was under the detection limit in the low
      producing strain. This study indicates that the high-SEA-producing strains,
      especially the strains with the putative capacity of prophage induction, could be
      more relevant in food safety aspects than low-producing type of strains on pork
      sausage. 

PMID- 24859190
TI  - Evidence for a reversible drought induced shift in the species composition of
      mycotoxin producing Fusarium head blight pathogens isolated from symptomatic
      wheat heads.
AB  - Fusarium species are fungal plant pathogens producing toxic secondary metabolites
      such as deoxynivalenol (DON), 15-acetyl-deoxynivalenol (15AcDON) and nivalenol
      (NIV). In Luxembourg, the Fusarium species composition isolated from symptomatic
      winter wheat heads was dominated by Fusarium graminearum sensu stricto strains
      (genetic 15AcDON chemotype) between the years 2009 and 2012, except for 2011,
      when Fusarium culmorum strains (genetic NIV chemotype) dominated the pathogen
      complex. Previous reports indicated that F. graminearum sensu stricto (genetic
      15AcDON chemotype) was also most frequently isolated from randomly sampled winter
      wheat kernels including symptomatic as well as asymptomatic kernels in 2007 and
      2008. The annual precipitation (average of 10 weather stations scattered across
      the country) decreased continuously from 924.31mm in 2007 over 917.15mm in 2008,
      to 843.38mm in 2009, 736.24mm in 2010, and 575.09mm in 2011. In 2012, the annual
      precipitation increased again to 854.70mm. Hardly any precipitation was recorded
      around the time of wheat anthesis in the years 2010 and 2011, whereas
      precipitation levels >50mm within the week preceding anthesis plus the week post
      anthesis were observed in the other years. The shift to genetic NIV chemotype F.
      culmorum strains in 2011 was accompanied by a very minor elevation of average NIV
      contents (2.9ngg(-1)) in the grain. Our data suggest that high NIV levels in
      Luxembourgish winter wheat are at present rather unlikely, because the indigenous
      F. culmorum strains with the genetic NIV chemotype seem to be outcompeted under
      humid in vivo conditions by F. graminearum DON producing strains on the one hand
      and seem to be inhibited - even though to a lower extent than DON producing
      strains - under dry in vivo conditions on the other hand. 

PMID- 24859192
TI  - Successful kidney transplant in a patient with IgG anti HLA Class-I auto
      antibodies: a case report.
AB  - Donor specific antibodies (DSA) play a significant role in graft rejection. Many
      laboratory methods, varied in sensitivity and specificity, are used to detect
      them. We report a case of a 38-year-old man presented with end stage renal
      disease considered for kidney transplantation. He had no history of blood
      transfusions nor transplantation procedures. Dilemma rose when he got multiple
      positive crossmatches with matching donors and a positive autologous crossmatch
      due to IgG anti HLA auto-antibodies, which are at the same time against matched
      donors. Since positive crossmatch is a contraindication for transplant, we
      couldn't perform transplant from any matched donor. Therefore, we considered a
      total mismatched donor then transplantation was performed. Observation after
      surgery showed normalization of creatinine, blood pressure and a good function of
      the planted allograft for two years of follow up.

PMID- 24859193
TI  - Stabilizing effect of beta-cyclodextrin on Limaprost, a PGE1 derivative, in
      Limaprost alfadex tablets (Opalmon) in highly humid conditions.
AB  - Stabilization against humidity of Limaprost (a prostaglandin E1 derivative),
      which is currently marketed as Opalmon, was undertaken using beta-cyclodextrin
      (beta-CD). Aqueous solutions of Limaprost alfadex/dextran 40 were lyophilized
      with and without beta-CD. Limaprost alfadex lyophilized with beta-CD was more
      chemically stable in humid conditions than that without beta-CD. Moreover, the
      addition of beta-CD as an excipient to tablets of these lyophilized composites
      remarkably improved the stability of Limaprost, and Limaprost in this moisture
      resistant formulation was chemically stable for 19 weeks at 30 degrees C, 75%
      relative humidity (R.H.). Chemical analysis of Limaprost and its degradation
      products indicated that degradation proceeded in the inclusion form (i.e., within
      the CD cavity). Solid (2)H-NMR spectroscopic studies showed that beta-CD
      constrained the molecular mobility of water in the solid state. These results
      suggested that the stabilization of Limaprost by beta-CD was at least partly due
      to the restricted molecular mobility of water, which acted as a catalytic species
      for the degradation, and also to the protection of the five-membered ring of
      Limaprost from water catalytic dehydration through inclusion complex formation
      with beta-CD.

PMID- 24859191
TI  - Evaluation of right ventricle functions and serotonin levels during headache
      attacks in migraine patients with aura.
AB  - Several studies suggested that headache attacks and its frequency were mainly
      responsible for increased cardiovascular (CV) disease and mortality in patients
      with migraine with aura (MWA). Elevated serotonin level has been found to play a
      role in migraine attacks. Serotonin was best studied within the CV system for its
      role in the development of pulmonary hypertension, which had negative impact on
      right ventricular (RV) functions. Therefore, in this study we aimed to evaluate
      RV functions during headache attacks in MWA patients and its relation to attack
      frequency with the utility of 2-dimensional speckle tracking echocardiography (2D
      STE). Fifty-three patients with the diagnosis of MWA were enrolled in the study.
      All patients were evaluated by conventional and 2D-STE echocardiography and
      venous blood sampling for serotonin was obtained during headache-free period
      (HFP) and headache-attack period (HAP). Also, patients were divided into two
      groups according to attack frequency. Patients exhibited higher serotonin levels
      during HAP than HFP (p < 0.001). Regarding 2D-STE derived RV-free-strain
      parameters, patients had lower RV-free wall longitudinal speckle-tracking strain
      (RV-free-ST), RV-free systolic strain rate (RV-free-STR-S), RV-free early
      diastolic strain rate (RV-free-STR-E) and RV-free-STR-E/A ratio levels during HAP
      when compared with HFP (p 0.002, p 0.006, p < 0.001 and p 0.001, respectively).
      Thirty-one patients (58.4 %) had low-frequency attack. Patients with high
      frequency attacks had increased serotonin levels (p 0.040) and decreased RV-free
      ST, RV-free-STR-S, RV-free-STR-E and RV-free-STR-E/A ratio values during HAP when
      compared to low-frequency group (p 0.026, p 0.029, p 0.037 and p 0.019
      respectively). This study demonstrated that migraine attacks, especially at
      higher frequencies, could have negative impact on RV systolic functions in MWA
      patients.

PMID- 24859194
TI  - Presence of biofilms on ultrafiltration membrane surfaces increases the quality
      of permeate produced during ultra-low pressure gravity-driven membrane
      filtration.
AB  - This study evaluates the effect of the presence of biofilms on membrane surfaces
      on the quality of permeate produced during Gravity-driven membrane
      ultrafiltration. GDM ultrafiltration is applied to the decentralized production
      of drinking water. A second objective was to evaluate to what extent permeate
      quality is enhanced by pre-treating feed-water (using a packed bed biofilm
      reactor or a slow sand filter). The influence of the ageing of the biofilm on the
      permeate quality was evaluated and compared to the effect of virgin membranes.
      Permeate quality was evaluated in terms of Assimilable Organic Carbon (AOC)
      content and dissolved organic carbon fractions (e.g. biopolymers). Our results
      indicate that virgin ultrafiltration membrane remove a small fraction of the AOC
      and biopolymers (rejection <10%). The presence of a young and thin biofilm on the
      surface of the ultrafiltration membranes increases the permeate quality due to
      the degradation of AOC (>80%). However, over long-term the hydrolysis of the
      organic matter that accumulated on membrane surfaces increases the AOC content of
      the permeate, thus deteriorating the permeate quality. Pre-treatment of the feed
      water help to control the biofilm accumulation and thus to limit the
      deterioration of the permeate quality. Permeate flux stabilised at average values
      of 7.5-8.9 L m(-2) h(-1). But the presence of pre-treatment helped to increase
      permeate flux (+12 and 19%, with the packed bed biofilm reactor and with the slow
      sand filter, respectively). Overall our study demonstrates that tolerating the
      presence of biofilm on membrane surface has a beneficial effect on the quality of
      permeate even if its quantity is decreased. 

PMID- 24859195
TI  - Characterization of biofilm and corrosion of cast iron pipes in drinking water
      distribution system with UV/Cl2 disinfection.
AB  - The effect of UV/Cl2 disinfection on the biofilm and corrosion of cast iron pipes
      in drinking water distribution system were studied using annular reactors (ARs).
      Passivation occurred more rapidly in the AR with UV/Cl2 than in the one with Cl2
      alone, decreasing iron release for higher corrosivity of water. Based on
      functional gene, pyrosequencing assays and principal component analysis, UV
      disinfection not only reduced the required initial chlorine dose, but also
      enhanced denitrifying functional bacteria advantage in the biofilm of corrosion
      scales. The nitrate-reducing bacteria (NRB) Dechloromonas exhibited the greatest
      corrosion inhibition by inducing the redox cycling of iron to enhance the
      precipitation of iron oxides and formation of Fe3O4 in the AR with UV/Cl2, while
      the rhizobia Bradyrhizobium and Rhizobium, and the NRB Sphingomonas, Brucella
      producing siderophores had weaker corrosion-inhibition effect by capturing iron
      in the AR with Cl2. These results indicated that the microbial redox cycling of
      iron was possibly responsible for higher corrosion inhibition and lower effect of
      water Larson-Skold Index (LI) changes on corrosion. This finding could be applied
      toward the control of water quality in drinking water distribution systems. 

PMID- 24859196
TI  - Promoter hypermethylation influences the suppressive role of maternally expressed
      3, a long non-coding RNA, in the development of epithelial ovarian cancer.
AB  - Maternally expressed 3 (MEG3) is a long non-coding RNA that can activate p53 and
      inhibit tumorigenesis and progression of various types of cancers. However, the
      role of MEG3 in epithelial ovarian cancer (EOC) is still unknown. The aim of the
      present study was to confirm whether MEG3 is downregulated in human EOC,
      determine its possible mechanism of action and elucidate the role of MEG3 in EOC.
      Differences in the expression of MEG3 and in the methylation status of the MEG3
      promoter between EOC and normal ovary were analyzed using RT-PCR and methylation
      specific PCR (MSP), respectively. MTT and EdU assays and flow cytometric analysis
      were used to assess the growth of ovarian cancer cells after overexpression of
      MEG3. The target genes regulated by MEG3 were detected with the Dual Luciferase
      Reporter system. The expression levels of target genes were confirmed using RT
      PCR and western blotting. In contrast to normal ovarian tissues, the expression
      of MEG3 was absent or decreased in most EOC tissues as well as in human EOC cell
      lines, and the promoter of the MEG3 gene was highly methylated in both cancer
      tissues and cell lines. Treatment with 5-aza-2-deoxycytidine reversed the
      promoter hypermethylation and increased MEG3 expression. In addition, ectopic
      expression of MEG3 suppressed the proliferation and growth of OVCAR3 cells and
      promoted apoptosis. Finally, MEG3 activated p53 in OVCAR3 cells. In conclusion,
      our data suggest that MEG3 is epigenetically silenced in EOC due to promoter
      hypermethylation, which may contribute to the development of EOC.

PMID- 24859197
TI  - Exercise training improves breathing strategy and performance during the six
      minute walk test in obese adolescents.
AB  - OBJECTIVES: We aimed to examine ventilatory responses during the six-minute walk
      test in healthy-weight and obese adolescents before and after exercise training.
      METHODS: Twenty obese adolescents (OB) (age: 14.5+/-1.7 years; BMI: 34.0+/
      4.7kg.m(-2)) and 20 age and gender-matched healthy-weight adolescents (HW) (age:
      15.5+/-1.5 years; BMI: 19.9+/-1.4kg.m(-2)) completed six-minute walk test during
      which breath-by-breath gas analysis and expiratory flow limitation (expFL) were
      measured. OB participated in a 12-week exercise-training program. RESULTS:
      Comparison between HW and OB participants showed lower distance achieved during
      the 6MWT in OB (-111.0m, 95%CI: -160.1 to 62.0, p<0.05) and exertional
      breathlessness was greater (+0.78 a.u., 95%CI: 0.091-3.27, p=0.039) when compared
      with HW. Obese adolescents breathed at lower lung volumes, as evidenced by lower
      end expiratory and end inspiratory lung volumes during exercise (p<0.05).
      Prevalence of expFL (8 OB vs 2 HW, p=0.028) and mean expFL (14.9+/-21.9 vs 5.32+/
      14.6% VT, p=0.043, in OB and HW) were greater in OB. After exercise training,
      mean increase in the distance achieved during the 6MWT was 64.5 meters (95%CI:
      28.1-100.9, p=0.014) and mean decrease in exertional breathlessness was 1.62
      (95%CI: 0.47-2.71, p=0.05). Obese adolescents breathed at higher lung volumes, as
      evidenced by the increase in end inspiratory lung volume from rest to 6-min
      exercise (9.9+/-13.4 vs 20.0+/-13.6%TLC, p<0.05). Improved performance was
      associated with improved change in end inspiratory lung volume from rest to 6-min
      exercise (r=0.65, p=0.025). CONCLUSION: Our results suggest that exercise
      training can improve breathing strategy during submaximal exercise in obese
      adolescents and that this increase is associated with greater exercise
      performance.

PMID- 24859198
TI  - A framework for accurate determination of the T2 distribution from multiple echo
      magnitude MRI images.
AB  - Measurement of the T2 distribution in tissues provides biologically relevant
      information about normal and abnormal microstructure and organization. Typically,
      the T2 distribution is obtained by fitting the magnitude MR images acquired by a
      multi-echo MRI pulse sequence using an inverse Laplace transform (ILT) algorithm.
      It is well known that the ideal magnitude MR signal follows a Rician
      distribution. Unfortunately, studies attempting to establish the validity and
      efficacy of the ILT algorithm assume that these input signals are Gaussian
      distributed. Violation of the normality (or Gaussian) assumption introduces
      unexpected artifacts, including spurious cerebrospinal fluid (CSF)-like long T2
      components; bias of the true geometric mean T2 values and in the relative
      fractions of various components; and blurring of nearby T2 peaks in the T2
      distribution. Here we apply and extend our previously proposed magnitude signal
      transformation framework to map noisy Rician-distributed magnitude multi-echo MRI
      signals into Gaussian-distributed signals with high accuracy and precision. We
      then perform an ILT on the transformed data to obtain an accurate T2
      distribution. Additionally, we demonstrate, by simulations and experiments, that
      this approach corrects the aforementioned artifacts in magnitude multi-echo MR
      images over a large range of signal-to-noise ratios. 

PMID- 24859199
TI  - ALK5-dependent TGF-beta signaling is a major determinant of late-stage adult
      neurogenesis.
AB  - The transforming growth factor-beta (TGF-beta) signaling pathway serves critical
      functions in CNS development, but, apart from its proposed neuroprotective
      actions, its physiological role in the adult brain is unclear. We observed a
      prominent activation of TGF-beta signaling in the adult dentate gyrus and
      expression of downstream Smad proteins in this neurogenic zone. Consistent with a
      function of TGF-beta signaling in adult neurogenesis, genetic deletion of the TGF
      beta receptor ALK5 reduced the number, migration and dendritic arborization of
      newborn neurons. Conversely, constitutive activation of neuronal ALK5 in
      forebrain caused a marked increase in these aspects of neurogenesis and was
      associated with higher expression of c-Fos in newborn neurons and with stronger
      memory function. Our findings describe an unexpected role for ALK5-dependent TGF
      beta signaling as a regulator of the late stages of adult hippocampal
      neurogenesis, which may have implications for changes in neurogenesis during
      aging and disease. 

PMID- 24859200
TI  - Mutations in Eml1 lead to ectopic progenitors and neuronal heterotopia in mouse
      and human.
AB  - Neuronal migration disorders such as lissencephaly and subcortical band
      heterotopia are associated with epilepsy and intellectual disability. DCX,
      PAFAH1B1 and TUBA1A are mutated in these disorders; however, corresponding mouse
      mutants do not show heterotopic neurons in the neocortex. In contrast,
      spontaneously arisen HeCo mice display this phenotype, and our study revealed
      that misplaced apical progenitors contribute to heterotopia formation. While HeCo
      neurons migrated at the same speed as wild type, abnormally distributed dividing
      progenitors were found throughout the cortical wall from embryonic day 13. We
      identified Eml1, encoding a microtubule-associated protein, as the gene mutated
      in HeCo mice. Full-length transcripts were lacking as a result of a
      retrotransposon insertion in an intron. Eml1 knockdown mimicked the HeCo
      progenitor phenotype and reexpression rescued it. We further found EML1 to be
      mutated in ribbon-like heterotopia in humans. Our data link abnormal spindle
      orientations, ectopic progenitors and severe heterotopia in mouse and human. 

PMID- 24859201
TI  - Active, phosphorylated fingolimod inhibits histone deacetylases and facilitates
      fear extinction memory.
AB  - FTY720 (fingolimod), an FDA-approved drug for treatment of multiple sclerosis,
      has beneficial effects in the CNS that are not yet well understood, independent
      of its effects on immune cell trafficking. We show that FTY720 enters the
      nucleus, where it is phosphorylated by sphingosine kinase 2 (SphK2), and that
      nuclear FTY720-P binds and inhibits class I histone deacetylases (HDACs),
      enhancing specific histone acetylations. FTY720 is also phosphorylated in mice
      and accumulates in the brain, including the hippocampus, inhibits HDACs and
      enhances histone acetylation and gene expression programs associated with memory
      and learning, and rescues memory deficits independently of its immunosuppressive
      actions. Sphk2(-/-) mice have lower levels of hippocampal sphingosine-1
      phosphate, an endogenous HDAC inhibitor, and reduced histone acetylation, and
      display deficits in spatial memory and impaired contextual fear extinction. Thus,
      sphingosine-1-phosphate and SphK2 play specific roles in memory functions and
      FTY720 may be a useful adjuvant therapy to facilitate extinction of aversive
      memories. 

PMID- 24859202
TI  - Mechanical coupling maintains the fidelity of NMDA receptor-mediated currents.
AB  - The fidelity of integration of pre- and postsynaptic activity by NMDA receptors
      (NMDARs) requires a match between agonist binding and ion channel opening. To
      address how agonist binding is transduced into pore opening in NMDARs, we
      manipulated the coupling between the ligand-binding domain (LBD) and the ion
      channel by inserting residues in a linker between them. We found that a single
      residue insertion markedly attenuated the ability of NMDARs to convert a
      glutamate transient into a functional response. This was largely a result of a
      decreased likelihood of the channel opening and remaining open. Computational and
      thermodynamic analyses suggest that insertions prevent the agonist-bound LBD from
      effectively pulling on pore lining elements, thereby destabilizing pore opening.
      Furthermore, this pulling energy was more prominent in the GluN2 subunit. We
      conclude that an efficient NMDAR-mediated synaptic response relies on a
      mechanical coupling between the LBD and the ion channel. 

PMID- 24859203
TI  - Effects of vedolizumab induction therapy for patients with Crohn's disease in
      whom tumor necrosis factor antagonist treatment failed.
AB  - BACKGROUND & AIMS: There is an increasing need for new treatments for patients
      with Crohn's disease (CD) in whom previous therapy with tumor necrosis factor
      (TNF) antagonists has failed. We performed a placebo-controlled, phase 3, double
      blind trial to evaluate the efficacy and safety of vedolizumab, an antibody
      against the integrin alpha4beta7, as induction therapy. METHODS: Patients with
      moderately to severely active CD (CD activity index [CDAI] score, 220-400 points)
      were assigned randomly to groups given vedolizumab (300 mg) or placebo
      intravenously at weeks 0, 2, and 6. The primary analysis involved 315 patients
      with previous TNF antagonist failure (ie, an inadequate response to, loss of
      response to, or intolerance of >=1 TNF antagonists); we determined the proportion
      of patients in clinical remission (CDAI, <=150 points) at week 6. Secondary
      analyses evaluated outcomes at weeks 6 and 10 in this population and in the
      overall population (N = 416), which included patients naive to TNF antagonist
      therapy (n = 101). RESULTS: Among patients who had experienced previous TNF
      antagonist failure, 15.2% of those given vedolizumab and 12.1% of those given
      placebo were in remission at week 6 (P = .433). At week 10, a higher proportion
      of this population given vedolizumab was in remission (26.6%) than those given
      placebo (12.1%) (nominal P = .001; relative risk, 2.2; 95% confidence interval,
      1.3-3.6). A higher proportion of patients with previous TNF antagonist failure
      given vedolizumab also had a CDAI-100 response (>=100-point decrease in CDAI
      score from baseline) at week 6 than those given placebo (39.2% vs 22.3%; nominal
      P = .001; relative risk, 1.8; 95% confidence interval, 1.2-2.5). Adverse event
      results were similar among all groups. CONCLUSIONS: Vedolizumab was not more
      effective than placebo in inducing clinical remission at week 6 among patients
      with CD in whom previous treatment with TNF antagonists had failed. The
      therapeutic benefits of vedolizumab in these patients were detectable at week 10.
      ClinicalTrials.gov number: NCT01224171.

PMID- 24859204
TI  - Detection of a sexually transmitted hepatitis C virus protease inhibitor
      resistance variant in a human immunodeficiency virus-infected homosexual man.
AB  - There is an international epidemic of hepatitis C virus (HCV) infection among
      human immunodeficiency virus-infected men who have sex with men. Transmission of
      HCV variants that are resistant to recently approved direct-acting antivirals
      (DAAs) could be an important clinical and public health problem. We document a
      case of transmission of a DAA-resistant variant of HCV from a patient who was
      treated with telaprevir to his sexual partner. The transmission of HCV DAA
      resistant variants could impair therapeutic regimens that include DAAs. 

PMID- 24859206
TI  - Stem cells marked by the R-spondin receptor LGR5.
AB  - Since the discovery of LGR5 as a marker of intestinal stem cells, the field has
      developed explosively and led to many new avenues of research. The inner workings
      of the intestinal crypt stem cell niche are now well understood. The study of
      stem cell-enriched genes has uncovered some previously unknown aspects of the Wnt
      signaling pathway, the major driver of crypt dynamics. LGR5(+) stem cells can now
      be cultured over long periods in vitro as epithelial organoids or "mini-guts."
      This technology opens new possibilities of using cultured adult stem cells for
      drug development, disease modeling, gene therapy, and regenerative medicine. This
      review describes the rediscovery of crypt base columnar cells as LGR5(+) adult
      stem cells and summarizes subsequent progress, promises, unresolved issues, and
      challenges of the field.

PMID- 24859207
TI  - Biohydrogen and polyhydroxyalkanoate co-production by Enterobacter aerogenes and
      Rhodobacter sphaeroides from Calophyllum inophyllum oil cake.
AB  - The feasibility of coupled biohydrogen and polyhydroxyalkanoate production by
      Enterobacter aerogenes and Rhodobacter sphaeroides using Calophyllum inophyllum
      oil cake was studied under dark and photo fermentation conditions. The
      utilization of a non-edible acidic oil cake (C. inophyllum), and exploitation of
      a modified minimal salt media led to reduction in the cost of media. Cost of
      fermentation is reduced by implementation of alternate dark-photo fermentative
      periods and through the use of a co-culture consisting of a dark fermentative (E.
      aerogenes) and a photo fermentative (R. sphaeroides) bacterium. The biohydrogen
      and polyhydroxyalkanoate produced were 7.95 L H2/L media and 10.73 g/L media,
      respectively, under alternate dark and photo fermentation and were 3.23 L H2/L
      media and 5.6g/L media, respectively under complete dark fermentation. The
      characteristics of the oil cake and alternate dark (16 h) and photo (8h)
      fermentative conditions were found to be supportive in producing high biohydrogen
      and polyhydroxyalkanoate (PHA) yield.

PMID- 24859209
TI  - Spontaneous modification of graphite anode by anthraquinone-2-sulfonic acid for
      microbial fuel cells.
AB  - In this study, anthraquinone-2-sulfonic acid (AQS), an electron transfer
      mediator, was immobilized onto graphite felt surface via spontaneous reduction of
      the in situ generated AQS diazonium cations. Cyclic voltammetry (CV) and energy
      dispersive spectrometry (EDS) characterizations of AQS modified graphite
      demonstrated that AQS was covalently grafted onto the graphite surface. The
      modified graphite, with a surface AQS concentration of 5.37 +/- 1.15 * 10(
      9)mol/cm(2), exhibited good electrochemical activity and high stability. The
      midpoint potential of the modified graphite was about -0.248 V (vs. normal
      hydrogen electrode, NHE), indicating that electrons could be easily transferred
      from NADH in bacteria to the electrode. AQS modified anode in MFCs increased the
      maximum power density from 967 +/- 33 mW/m(2) to 1872 +/- 42 mW/m(2). These
      results demonstrated that covalently modified AQS functioned as an electron
      transfer mediator to facilitate extracellular electron transfer from bacteria to
      electrode and significantly enhanced the power production in MFCs.

PMID- 24859208
TI  - Influence of reaction atmosphere and solvent on biochar yield and
      characteristics.
AB  - Sunflower husks were converted to biochar via thermochemical liquefaction in
      different solvents and reaction atmospheres. Highest biochar yields obtained was
      574 g kg(-1) husks. Surface area of the produced chars and evolution of aromatic
      compounds in the biochar structure increased with an increase in temperature.
      Volatile matter and N-content decreased and S-content decreased significantly
      with an increase in temperature which is favourable should the biochars be used
      for combustion. The HHV of the biochars were significantly higher than that of
      the feedstock as was also indicated by the energy densification ratio. The
      biochars compared favourable with coal on a Van Krevelen diagram, showing the
      possibility of the biochars for application in co-gasification. CO2 performed
      better in retaining the energy of the feedstock in the biochar (up to 58%). It
      was shown that sunflower husks are a viable feedstock for the production of
      biochars for application in co-gasification or combustion.

PMID- 24859205
TI  - CpG island methylator phenotype is associated with response to adjuvant
      irinotecan-based therapy for stage III colon cancer.
AB  - BACKGROUND & AIMS: The CpG island methylator phenotype (CIMP), defined by a high
      frequency of aberrantly methylated genes, is a characteristic of a subclass of
      colon tumors with distinct clinical and molecular features. Cohort studies have
      produced conflicting results on responses of CIMP-positive tumors to
      chemotherapy. We assessed the association between tumor CIMP status and survival
      of patients receiving adjuvant fluorouracil and leucovorin alone or with
      irinotecan (IFL). METHODS: We analyzed data from patients with stage III colon
      adenocarcinoma randomly assigned to groups given fluorouracil and leucovorin or
      IFL after surgery, from April 1999 through April 2001. The primary end point of
      the trial was overall survival and the secondary end point was disease-free
      survival. DNA isolated from available tumor samples (n = 615) was used to
      determine CIMP status based on methylation patterns at the CACNA1G, IGF2,
      NEUROG1, RUNX3, and SOCS1 loci. The effects of CIMP on survival were modeled
      using Kaplan-Meier and Cox proportional hazards; interactions with treatment and
      BRAF, KRAS, and mismatch repair (MMR) status were also investigated. RESULTS: Of
      the tumor samples characterized for CIMP status, 145 were CIMP positive (23%).
      Patients with CIMP-positive tumors had shorter overall survival times than
      patients with CIMP-negative tumors (hazard ratio = 1.36; 95% confidence interval:
      1.01-1.84). Treatment with IFL showed a trend toward increased overall survival
      for patients with CIMP-positive tumors, compared with treatment with fluorouracil
      and leucovorin (hazard ratio = 0.62; 95% CI: 0.37-1.05; P = .07), but not for
      patients with CIMP-negative tumors (hazard ratio = 1.38; 95% CI: 1.00-1.89; P =
      .049). In a 3-way interaction analysis, patients with CIMP-positive, MMR-intact
      tumors benefited most from the addition of irinotecan to fluorouracil and
      leucovorin therapy (for the interaction, P = .01). CIMP was more strongly
      associated with response to IFL than MMR status. Results for disease-free
      survival times were comparable among all analyses. CONCLUSIONS: Patients with
      stage III, CIMP-positive, MMR-intact colon tumors have longer survival times when
      irinotecan is added to combination therapy with fluorouracil and leucovorin.

PMID- 24859210
TI  - Use of biochars in anaerobic digestion.
AB  - This study investigated the behavior of biochars from pyrolysis (pyrochar) and
      hydrothermal carbonization (hydrochar) in anaerobic digestion regarding their
      degradability and their effects on biogas production and ammonia inhibition. A
      batch fermentation experiment (42 degrees C, 63 days) was conducted in 100mL
      syringes filled with 30 g inoculum, 2g biochar and four levels of total ammonium
      nitrogen (TAN). For pyrochar, no clear effect on biogas production was observed,
      whereas hydrochar increased the methane yield by 32%. This correlates with the
      hydrochar's larger fraction of anaerobically degradable carbon (10.4% of total
      carbon, pyrochar: 0.6%). Kinetic and microbiota analyses revealed that pyrochar
      can prevent mild ammonia inhibition (2.1 g TANk g(-1)). Stronger inhibitions (3.1
      6.6 g TAN kg(-1)) were not mitigated, neither by pyrochar nor by hydrochar.
      Future research should pay attention to biochar-microbe interactions and the
      effects in continuously-fed anaerobic digesters.

PMID- 24859211
TI  - Combination of ultrasonic irradiation with ionic liquid pretreatment for
      enzymatic hydrolysis of rice straw.
AB  - The application of ultrasonic irradiation and ionic liquids (ILs) in the
      degradation of rice straw under different processes of pretreatment and enzymatic
      hydrolysis was investigated. Various substrates for enzymatic hydrolysis by
      cellulase with and without ultrasound were as follows: untreated rice-straw
      powder (RS); RS treated by ILs of 1-ethyl-3-methylimidazolium ethylsulfate and
      trihexyl (tetradecyl) phosphonium decanoate with ultrasound at 300 W/(40 kHz, 28
      kHz); RS treated by IL of choline hydroxide ([Ch][OH]) with ultrasound at 300
      W/40 kHz (CHRS). In ultrasound-mediated enzymatic hydrolysis, the yield of total
      reducing sugar (TRS) converted from CHRS was up to 96.22% at 240 min and was
      greater than that from the other substrates; the TRS yield for CHRS with
      ultrasound was 19.5% greater than that without irradiation. Lignocellulosic
      biomass pretreated with [Ch][OH] showed the highest efficiency among the tested
      ILs, and ultrasound can be applied effectively in rice-straw pretreatment and
      enzymatic hydrolysis.

PMID- 24859212
TI  - Treatment of hypersaline produced water employing a moderately halophilic
      bacterial consortium in a membrane bioreactor: effect of salt concentration on
      organic removal performance, mixed liquor characteristics and membrane fouling.
AB  - In this study the organic pollutant removal performance and the mixed liquor
      characteristics of a membrane bioreactor (MBR), employing a moderately halophilic
      bacterial consortium, for the treatment of hypersaline synthetic produced water
      containing 100-250 g L(-1) NaCl were considered. The COD and oil and grease (O&G)
      removal efficiencies in the range 81.6-94.6% and 84.8-94.0% respectively and MBR
      effluent turbidity lower than 2NTU were achieved. There was no pronounced
      membrane fouling at any salt concentration. O&G accumulation (less than 11% of
      the influent O&G) occurred in the mixed liquor at all salt concentrations, but
      biodegradation was identified as the major organic removal mechanism. With
      increasing salt concentration, initially increase in SVI and later formation of
      oil/biomass bodies took place but due to the presence of the membrane biomass
      washout did not occur. The mixed liquor was pseudoplastic and the apparent
      viscosity and flow behavior index generally increased with salt concentration.

PMID- 24859213
TI  - The effect of nutrition pattern alteration on Chlorella pyrenoidosa growth, lipid
      biosynthesis-related gene transcription.
AB  - Heterotrophy to photoautotrophy transition leads to the accumulation of lipids in
      Chlorella, which has potential to produce both healthy food and biofuels.
      Therefore, it is of key interest to study the metabolism shift and gene
      expression changes that influenced by the transition. Both total and neutral
      lipids contents were increased rapidly within 48 h after the switch to light
      environment, from 24.5% and 18.0% to 35.3% and 27.4%, respectively, along with
      the sharp decline of starch from 42.3% to 10.4% during 24h photoinduction phase.
      By analyzing the correlation between lipid content and gene expression, results
      revealed several genes viz. me g3137, me g6562, pepc g6833, dgat g3280 and dgat
      g7566, which encode corresponding enzymes in the de novo lipid biosynthesis
      pathway, are highly related to lipid accumulation and might be exploited as
      target genes for genetic modification. These results represented the feasibility
      of lipid production through trophic converting cultivation.

PMID- 24859214
TI  - Comparative study on two-step concentrated acid hydrolysis for the extraction of
      sugars from lignocellulosic biomass.
AB  - Among all the feasible thermochemical conversion processes, concentrated acid
      hydrolysis has been applied to break the crystalline structure of cellulose
      efficiently and scale up for mass production as lignocellulosic biomass
      fractionation process. Process conditions are optimized by investigating the
      effect of decrystallization sulfuric acid concentration (65-80 wt%), hydrolysis
      temperature (80 degrees C and 100 degrees C), hydrolysis reaction time (during
      two hours), and biomass species (oak wood, pine wood, and empty fruit bunch (EFB)
      of palm oil) toward sugar recovery. At the optimum process condition, 78-96%
      sugars out of theoretically extractable sugars have been fractionated by
      concentrated sulfuric acid hydrolysis of the three different biomass species with
      87-90 g/L sugar concentration in the hydrolyzate and highest recalcitrance of
      pine (softwood) was determined by the correlation of crystallinity index and
      sugar yield considering reaction severity.

PMID- 24859215
TI  - Electrochemical stimulation of microbial reductive dechlorination of
      pentachlorophenol using solid-state redox mediator (humin) immobilization.
AB  - Immobilized solid-phase humin on a graphite electrode set at -500 mV (vs.
      standard hydrogen electrode) significantly enhanced the microbial reductive
      dechlorination of pentachlorophenol as a stable solid-phase redox mediator in
      bioelectrochemical systems (BESs). Compared with the suspended system, the
      immobilized system dechlorinated PCP at a much higher efficiency, achieving 116
      MUmol Cl(-)g(-1) humin d(-1). Fluorescence microscopy showed a conspicuous growth
      of bacteria on the negatively poised immobilized humin. Electron balance analyses
      suggested that the electrons required for microbial dechlorination were supplied
      primarily from the humin-immobilized electrode. Microbial community analyses
      based on 16S rRNA genes showed that Dehalobacter and Desulfovibrio grew on the
      immobilized humin as potential dechlorinators. These findings extend the
      potential of BESs using immobilized solid-phase humin as the redox mediator for
      in situ bioremediation, given the wide distribution of humin and its efficiency
      and stability as a mediator.

PMID- 24859216
TI  - Understanding intellectual disability through RASopathies.
AB  - Intellectual disability, commonly known as mental retardation in the
      International Classification of Disease from World Health Organization, is the
      term that describes an intellectual and adaptive cognitive disability that begins
      in early life during the developmental period. Currently the term intellectual
      disability is the preferred one. Although our understanding of the physiological
      basis of learning and learning disability is poor, a general idea is that such
      condition is quite permanent. However, investigations in animal models suggest
      that learning disability can be functional in nature and as such reversible
      through pharmacology or appropriate learning paradigms. A fraction of the cases
      of intellectual disability is caused by point mutations or deletions in genes
      that encode for proteins of the RAS/MAP kinase signaling pathway known as
      RASopathies. Here we examined the current understanding of the molecular
      mechanisms involved in this group of genetic disorders focusing in studies which
      provide evidence that intellectual disability is potentially treatable and
      curable. The evidence presented supports the idea that with the appropriate
      understanding of the molecular mechanisms involved, intellectual disability could
      be treated pharmacologically and perhaps through specific mechanistic-based
      teaching strategies. 

PMID- 24859218
TI  - Testosterone is essential for skeletal muscle growth in aged mice in a
      heterochronic parabiosis model.
AB  - As humans age, they lose both muscle mass and strength (sarcopenia).
      Testosterone, a circulating hormone, progressively declines in aging and is
      associated with loss of muscle mass and strength. The surgical joining of a young
      and old mouse (heterochronic parabiosis) activates Notch signaling and restores
      muscle regenerative potential in aged mice. We hypothesize that testosterone is
      at least one of the factors required for the improvement seen in muscles in old
      mice in heterochronic parabiosis with young mice. To test this hypothesis, we
      established the following heterochronic parabioses between young (Y; 5 months
      old) and old (O; 22-23 months old) C57BL6 male mice: (1) Y:O; (2) castrated Y:O
      (OY:O); (3) castrated + testosterone-treated Y:O (OY + T:O). A group of normal
      young mice received empty implants, and old mice were used as controls.
      Parabiotic pairings were maintained for 4 weeks prior to analysis. Serum
      testosterone levels were three-fold higher in young than in old mice. The OY +
      T:O pairing demonstrated significantly elevated levels of serum testosterone and
      an improvement in gastrocnemius muscle weight, muscle ultrastructure, muscle
      fiber cross-sectional area, and Notch-1 expression in old mice. These changes
      were not present in aged mice in the OY:O pairing. These data indicate that
      testosterone has a critical role in mediating the improved muscle mass and
      ultrastructure seen in an experimental model of heterochronic parabiosis. 

PMID- 24859217
TI  - Cell cycle regulation of proliferation versus differentiation in the central
      nervous system.
AB  - Formation of the central nervous system requires a period of extensive progenitor
      cell proliferation, accompanied or closely followed by differentiation; the
      balance between these two processes in various regions of the central nervous
      system gives rise to differential growth and cellular diversity. The correlation
      between cell cycle lengthening and differentiation has been reported across
      several types of cell lineage and from diverse model organisms, both in vivo and
      in vitro. Furthermore, different cell fates might be determined during different
      phases of the preceding cell cycle, indicating direct cell cycle influences on
      both early lineage commitment and terminal cell fate decisions. Significant
      advances have been made in the last decade and have revealed multi-directional
      interactions between the molecular machinery regulating the processes of cell
      proliferation and neuronal differentiation. Here, we first introduce the modes of
      proliferation in neural progenitor cells and summarise evidence linking cell
      cycle length and neuronal differentiation. Second, we describe the manner in
      which components of the cell cycle machinery can have additional and, sometimes,
      cell-cycle-independent roles in directly regulating neurogenesis. Finally, we
      discuss the way that differentiation factors, such as proneural bHLH proteins,
      can promote either progenitor maintenance or differentiation according to the
      cellular environment. These intricate connections contribute to precise
      coordination and the ultimate division versus differentiation decision. 

PMID- 24859219
TI  - Strontium ranelate changes the composition and crystal structure of the
      biological bone-like apatite produced in osteoblast cell cultures.
AB  - We evaluate the effects of strontium ranelate on the composition and crystal
      structure of the biological bone-like apatite produced in osteoblast cell
      cultures, a system that gave us the advantage of obtaining mineral samples
      produced exclusively during treatment. Cells were treated with strontium ranelate
      at concentrations of 0.05 and 0.5 mM Sr(2+). Mineral substances were isolated and
      analyzed by using a combination of methods: Fourier transform infrared
      spectroscopy, solid-state (1)H nuclear magnetic resonance, X-ray diffraction,
      micro-Raman spectroscopy and energy dispersive X-ray spectroscopy. The minerals
      produced in all cell cultures were typical bone-like apatites. No changes
      occurred in the local structural order or crystal size of the minerals. However,
      we noticed several relevant changes in the mineral produced under 0.5 mM Sr(2+):
      (1) increase in type-B CO3 (2-) substitutions, which often lead to the creation
      of vacancies in Ca(2+) and OH(-) sites; (2) incorporation of Sr(2+) by
      substituting slightly less than 10 % of Ca(2+) in the apatite crystal lattice,
      resulting in an increase in both lattice parameters a and c; (3) change in the
      PO4 (3-) environments, possibly because of the expansion of the lattice; (4) the
      Ca/P ratio of this mineral was reduced, but its (Ca+Sr)/P ratio was the same as
      that of the control, indicating that its overall cation/P ratio was preserved.
      Thus, strontium ranelate changes the composition and crystal structure of the
      biological bone-like apatite produced in osteoblast cell cultures. 

PMID- 24859220
TI  - Primary alveolar macrophages exposed to diesel particulate matter increase RAGE
      expression and activate RAGE signaling.
AB  - Receptors for advanced glycation end-products (RAGE) are members of the
      immunoglobulin superfamily of cell-surface receptors implicated in mechanisms of
      pulmonary inflammation. In the current study, we test the hypothesis that RAGE
      mediates inflammation in primary alveolar macrophages (AMs) exposed to diesel
      particulate matter (DPM). Quantitative RT-PCR and immunoblotting revealed that
      RAGE was up-regulated in Raw264.7 cells, an immortalized murine macrophage cell
      line and primary AMs exposed to DPM for 2 h. Because DPM increased RAGE
      expression, we exposed Raw264.7 cells and primary AMs isolated from RAGE null and
      wild-type (WT) mice to DPM prior to the assessment of inflammatory signaling
      intermediates. DPM led to the activation of Rat sarcoma GTPase (Ras), p38 MAPK
      and NF-kappaB in WT AMs and, when compared to WT AMs, these intermediates were
      diminished in DPM-exposed AMs isolated from RAGE null mice. Furthermore,
      cytokines implicated in inflammation, including IL-4, IL-12, IL-13 and TNFalpha,
      were all significantly decreased in DPM-exposed RAGE null AMs compared to
      similarly exposed WT AMs. These results demonstrate that diesel-induced
      inflammatory responses by primary AMs are mediated, at least in part, via RAGE
      signaling mechanisms. Further work may show that RAGE signaling in both alveolar
      epithelial cells and resident macrophages is a potential target in the treatment
      of inflammatory lung diseases exacerbated by environmental pollution.

PMID- 24859221
TI  - Effects of high glucose and high insulin concentrations on osteoblast function in
      vitro.
AB  - Bone disease as a consequence of diabetes mellitus (DM) is not fully understood.
      The effects of high glucose (30 mM), high insulin (50 nM), or mannitol (30 mM;
      osmotic control) were evaluated on MC3T3-E1 cells (osteoblasts) in vitro. The
      mRNA and protein levels of parathyroid hormone (PTH) receptor (PTH1R), collagen
      I, RANKL, osteoprotegerin (OPG), alkaline phosphatase (ALP), and glucose
      transporter (GLUT1) were estimated by real-time polymerase chain reaction or
      Western blotting. The mineralization capacity was analyzed by von Kossa staining.
      High glucose induced overexpression of RANKL (2*) and OPG (30*), suggesting that
      RANKL-induced osteoclast activity might not be a dominant mechanism of bone
      disease in DM, since this increase was followed by increased OPG. Collagen I
      increased by 12*, indicating an excess of organic matrix production. The
      expression of ALP decreased by 50%, indicating a deficit in mineralization
      capacity, confirmed by von Kossa staining. Mannitol induced similar effects as
      glucose suggesting that extracellular hyperosmolarity was able to stimulate
      organic matrix production. GLUT1 expression was not altered, and insulin did not
      reverse most of the effects of glucose, suggesting that glucose uptake by
      osteoblasts was not altered by high glucose. The data suggest that the bone
      fragility typical of DM is not a consequence of excessive bone reabsorption but
      is instead attributable to a defect in organic matrix mineralization. The
      heightened increase in OPG versus RANKL might cause a decrease in the bone
      remodeling cycle. Osteoblasts appear to be more sensitive to extracellular
      hypertonicity than to the intracellular metabolic effects of hyperglycemia.

PMID- 24859222
TI  - Musculoskeletal congenital malformations: do paternal occupational exposures play
      a role?
AB  - BACKGROUND: Paternal occupational exposures to potential health hazards are
      likely to affect congenital malformations through the spermatogenesis cycle.
      PURPOSE: The aim of this case-control study was to assess the relationship
      between the risk of musculoskeletal congenital malformations in offspring and
      paternal workplace exposure to potential health hazards during the preconception
      period. METHOD: The study comprised 105 patients (cases) with a musculoskeletal
      congenital malformation(s) and 135 controls matched for age and demographic
      characteristics. Both parents of each case and control were interviewed in the
      hospital by a trained physician. They also completed a questionnaire focusing on
      the preconception period and on the 3-month period immediately before and after
      the pregnancy conception date, respectively, of the child under study. RESULTS:
      The odds of having a child with a congenital malformation was higher (P < 0.05)
      if the father was occupationally exposed to pesticides, solvents, or welding
      fumes during the preconception period. CONCLUSION: Control of workplace exposures
      and adherence to threshold limit values of these potential health hazards should
      be adopted to minimize the risk of fathers having offspring with a congenital
      malformation.

PMID- 24859223
TI  - Reports of Elder Neglect by Older Adults, Their Family Caregivers, and Their Home
      Care Workers: A Test of Measurement Invariance.
AB  - OBJECTIVES: The present study evaluated the measurement invariance of a 7-item
      scale designed to assess elder neglect across three groups of informants: Older
      adults, family members, and home care workers. In addition, differential item
      functioning (DIF) was evaluated in order to examine whether individuals of
      certain characteristics have a different probability of endorsing certain items
      even at equivalent levels of the overall construct of neglect. METHOD: A cross
      sectional sample of 686 family members, 388 older adults, and 523 home care
      workers was drawn. A series of sequentially nested confirmatory factor models was
      examined to identify whether configural (the same items are associated with the
      same factor across groups), metric (factors have a similar meaning across
      groups), and scalar (group means can be meaningfully compared across groups)
      invariances can be established. Multi indicators multi causes analysis was
      conducted to identify DIF across age, gender, and education. RESULTS: Five items
      were adequate indicators of the overall construct. The findings provide support
      to configural, metric, and scalar invariances across the 3 groups of informants.
      None of the items resulted in DIF. DISCUSSION: The findings advocate for the use
      of the 5-item neglect scale across different groups of informants and call for
      the evaluation of elder neglect within the constellation of the caregiving unit.

PMID- 24859224
TI  - Multiple Object Tracking While Walking: Similarities and Differences Between
      Young, Young-Old, and Old-Old Adults.
AB  - OBJECTIVE: Walking while simultaneously engaged in another activity becomes more
      difficult as one grows older. Here, we address the issue of changes in dual-task
      behavior at different stages of life, particularly in the latter stages. METHODS:
      We developed a dual task that combined walking along an 8-m walkway with a
      multiple object tracking (MOT) task of increasing difficulty. This secondary
      cognitive task imitates visuospatial daily activities and provides reliable
      quantitative measurements. Our dual-task paradigm was tested on 27 young adults
      (23.85 +/- 2.09 years old) and two groups of older adults (18 young-old and 18
      old-old adults, aged 63.89 +/- 3.32 and 80.83 +/- 3.84 years, respectively).
      RESULTS: Significant decrease in tracking performance with increasing complexity
      of the MOT task was found in all three groups. An age-related decrease in MOT and
      gait performance was also found. However, young-old adults performed as well as
      young adults under low attentional load conditions (in the MOT task and simple
      walking), whereas their performance was as impaired as those of old-old adults
      under high attentional load conditions (in the MOT task and walking under dual
      task condition). DISCUSSION: These different profiles between the two groups of
      older participants could be explained in terms of compensation strategies and
      risk of falling.

PMID- 24859225
TI  - Age at migration and self-rated health trajectories after age 50: understanding
      the older immigrant health paradox.
AB  - OBJECTIVES: This research contributes to the "immigrant health paradox" debate by
      testing the hypothesis that older age at migration is associated with the
      increased risk of poor health in later life. METHOD: Using the 1992-2008 Health
      and Retirement Study, I construct linear random-intercept models to estimate self
      rated health (SRH) trajectories after age 50 for the native and foreign born by
      age at migration. RESULTS: At age 50, both Hispanic and non-Hispanic foreign born
      report better SRH compared with their native-born counterparts, net of race,
      gender, and education. Non-Hispanic foreign born who migrated after age 35 and
      Hispanic foreign born who migrated after age 18, however, experience steeper
      decline in SRH after age 50, which results in a health disadvantage vis-a-vis the
      native born in old age. Education has a smaller protective effect on SRH for the
      foreign born, especially those who migrated as adults. DISCUSSION: Age at
      migration is an important factor for understanding health status of older
      immigrants. Steeper health decline in later life of the foreign born who migrated
      in advanced ages may be related to longer exposure to unfavorable conditions in
      home countries and limited opportunities for incorporation in the United States.

PMID- 24859226
TI  - The role of the autophagy in myocardial ischemia/reperfusion injury.
AB  - Autophagy is an intracellular process responsible for damaged or unnecessary
      protein and organelle degradation. In the heart, autophagy occurs at basal level
      and dysregulated autophagy is associated with a variety of cardiovascular
      diseases. Autophagy is enhanced in ischemia as well as in the reperfusion phase
      during cardiac ischemia reperfusion (I/R) injury. More importantly, recent
      studies revealed that autophagy exerted both beneficial and detrimental effects
      in pathology of cardiac ischemia reperfusion. This paper is to review the
      functional significance of autophagy in cardiac ischemia reperfusion injury and
      discuss underlying signaling pathways. This article is part of a Special Issue
      entitled: Autophagy and protein quality control in cardiometabolic diseases. 

PMID- 24859227
TI  - Impact of D181V and A69T on the function of ferroportin as an iron export pump
      and hepcidin receptor.
AB  - Mutations in the only known mammalian iron exporter ferroportin cause a rare iron
      overload disorder termed ferroportin disease. Two distinct clinical phenotypes
      are caused by different disease mechanisms: mutations in ferroportin either cause
      loss of iron export function or gain of function due to resistance to hepcidin,
      the peptide hormone that normally downregulates ferroportin. The aim of the
      present study was to examine the disease mechanisms of the thus far unclassified
      A69T and D181V ferroportin mutations. We overexpressed wild-type and mutant
      ferroportin fused to green fluorescent protein in human embryonic kidney cells
      and used a (59)Fe-assay, intracellular ferritin concentrations, confocal
      microscopy and flow cytometry to study iron export function, subcellular
      localization and the responsiveness to hepcidin. While the A69T ferroportin
      mutation seems not to affect the iron export function it causes dose-dependent
      hepcidin resistance. We further found that D181V mutated ferroportin is iron
      export defective and hepcidin resistant, similar to the loss of function
      mutations A77D and C367X. This indicates that intact iron export might be
      necessary for hepcidin-induced downregulation of ferroportin. This hypothesis was
      investigated by studying the hepcidin response under modulation of iron
      availability. Incubation of wild-type ferroportin overexpressing cells with holo
      transferrin increases the hepcidin effect whereas chelating extracellular ferrous
      iron causes hepcidin resistance. In this study we present data that postulates to
      classify the D181V ferroportin mutation as loss of function and the A69T mutation
      as dose-dependent hepcidin resistant and outline a possible causal link between
      iron export function and the hepcidin effect. 

PMID- 24859228
TI  - Mitochondrial JNK activation triggers autophagy and apoptosis and aggravates
      myocardial injury following ischemia/reperfusion.
AB  - c-Jun N-terminal kinase (JNK) is a stress-activated mitogen-activated protein
      kinase that plays a central role in initiating apoptosis in disease conditions.
      Recent studies have shown that mitochondrial JNK signaling is partly responsible
      for ischemic myocardial dysfunction; however, the underlying mechanism remains
      unclear. Here we report for the first time that activation of mitochondrial JNK,
      rather than JNK localization on mitochondria, induces autophagy and apoptosis and
      aggravates myocardial ischemia/reperfusion injury. Myocardial
      ischemia/reperfusion induced a dominant increase of mitochondrial JNK
      phosphorylation, while JNK mitochondrial localization was reduced. Treatment with
      Tat-SabKIM1, a retro-inverso peptide which blocks JNK interaction with
      mitochondria, decreased mitochondrial JNK activation without affecting JNK
      mitochondrial localization following reperfusion. Tat-SabKIM1 treatment reduced
      Bcl2-regulated autophagy, cytochrome c-mediated apoptosis and myocardial infarct
      size. Notably, selective inhibition of mitochondrial JNK activation using Tat
      SabKIM1 produced a similar infarct size-reducing effect as inhibiting universal
      JNK activation with JNK inhibitor SP600125. Moreover, insulin-treated animals
      exhibited significantly dampened mitochondrial JNK activation accompanied by
      reduced infarct size and diminished autophagy and apoptosis following
      reperfusion. Taken together, these findings demonstrate that mitochondrial JNK
      activation, rather than JNK mitochondrial localization, induces autophagy and
      apoptosis and exacerbates myocardial ischemia/reperfusion injury. Insulin
      selectively inhibits mitochondrial JNK activation, contributing to insulin
      cardioprotection against myocardial ischemic/reperfusion injury. This article is
      part of a Special Issue entitled: Autophagy and protein quality control in
      cardiometabolic diseases. 

PMID- 24859231
TI  - Vertical migrations of a deep-sea fish and its prey.
AB  - It has been speculated that some deep-sea fishes can display large vertical
      migrations and likely doing so to explore the full suite of benthopelagic food
      resources, especially the pelagic organisms of the deep scattering layer (DSL).
      This would help explain the success of fishes residing at seamounts and the
      increased biodiversity found in these features of the open ocean. We combined
      active plus passive acoustic telemetry of blackspot seabream with in situ
      environmental and biological (backscattering) data collection at a seamount to
      verify if its behaviour is dominated by vertical movements as a response to
      temporal changes in environmental conditions and pelagic prey availability. We
      found that seabream extensively migrate up and down the water column, that these
      patterns are cyclic both in short-term (tidal, diel) as well as long-term
      (seasonal) scales, and that they partially match the availability of potential
      DSL prey components. Furthermore, the emerging pattern points to a more complex
      spatial behaviour than previously anticipated, suggesting a seasonal switch in
      the diel behaviour mode (benthic vs. pelagic) of seabream, which may reflect an
      adaptation to differences in prey availability. This study is the first to
      document the fine scale three-dimensional behaviour of a deep-sea fish residing
      at seamounts. 

PMID- 24859230
TI  - Intravenous methadone application as a serious risk factor for an overdose death:
      methadone-related fatalities in Hamburg from 2007 to 2012.
AB  - Methadone plays an increasing role in drug-related deaths in Hamburg. To find out
      whether intravenous application of methadone plays a relevant role in methadone
      related deaths, body fluids of all methadone-positive cases (n=130) and three
      buprenorphine-positive cases where a urine sample was available (n=58+3) were
      investigated for disaccharides (sucrose and lactose as markers for intravenous
      methadone abuse). Sixty-four percent of the urine samples of the methadone cases
      showed positive results for disaccharides (22 times sucrose alone, range 2 to
      >1,000 mg/L; 6 times lactose and sucrose; and 9 times lactose alone, range 22 to
      382 mg/L). The three buprenorphine cases showed positive results for lactose in
      urine. In blood, it was not possible to detect any disaccharides. Of the 116
      fatal methadone intoxications, 49 % were under opiate maintenance treatment (OMT)
      at the point of death (A-OMT), 30 % were never in OMT (N-OMT) and 21 % were
      formerly in an OMT, but not at the point of death (F-OMT). Of the deceased in the
      OMT group, 12 % (n=7) died within the first 2 weeks of treatment, six of them
      within the first week. Overall, intravenous abuse of methadone plays a relevant
      role in methadone-related fatal cases of substituted patients and of drug
      consumers not in therapy. Thus, it is necessary that therapists keep to the
      statutory regulations and give take-home doses only after at least 6 months of
      successful therapy and when there is no suspicion of intravenous abuse.

PMID- 24859232
TI  - Azo dye load-shock on relative behavior of biofilm and suspended growth
      configured periodic discontinuous batch mode operations: critical evaluation with
      enzymatic and bio-electrocatalytic analysis.
AB  - Effect of dye (C.I.Acid Black 10B) load-shock was comparatively evaluated in
      biofilm (self-immobilized) and suspended growth systems operated in periodic
      discontinuous batch mode (PDBR, anoxic-aerobic-anoxic) was investigated. At
      higher dye load (1250 mg dye/l), biofilm system showed relatively higher dye
      (74.5%) and COD (46%) removal efficiencies than the corresponding suspended mode
      operation (dye/COD removal efficiency, 42%/65%). Increment in dye load showed
      increment in azo reductase and dehydrogenase enzyme activities. Voltammograms
      (cyclic) showed higher reduction currents (RC) with increment in dye load
      specifically in biofilm system. Derivative cyclic voltammograms analysis depicted
      the involvement of mediators (NAD (+), FAD(+), etc.) which presumably played a
      major role in electron transport chain and dye degradation. Disappearance of peak
      (1612 cm(-1)) specific to azo group in FTIR spectrum, at higher loading rate in
      both the systems indicates the non-inhibitory and robust nature of PDBR
      operation. 

PMID- 24859229
TI  - Antibodies directed against receptor tyrosine kinases: current and future
      strategies to fight cancer.
AB  - Approximately 30 therapeutic monoclonal antibodies have already been approved for
      cancers and inflammatory diseases, and monoclonal antibodies continue to be one
      of the fastest growing classes of therapeutic molecules. Because aberrant
      signaling by receptor tyrosine kinases (RTKs) is a commonly observed factor in
      cancer, most of the subclasses of RTKs are being extensively studied as potential
      targets for treating malignancies. The first two RTKs that have been targeted by
      antibody therapy, with five currently marketed antibodies, are the growth factor
      receptors EGFR and HER2. However, due to systemic side effects, refractory
      patients and the development of drug resistance, these treatments are being
      challenged by emerging therapeutics. This review examines current monoclonal
      antibody therapies against RTKs. After an analysis of agents that have already
      been approved, we present an analysis of antibodies in clinical development that
      target RTKs. Finally, we highlight promising RTKs that are emerging as new
      oncological targets for antibody-based therapy. 

PMID- 24859233
TI  - Examination of the physical properties of Microcystis aeruginosa flocs produced
      on coagulation with metal salts.
AB  - Coagulation-flocculation (C-F) is a key barrier to cyanobacterial and algal cell
      infiltration in water treatment plants during seasonal blooms. However, the
      resultant cell floc properties, in terms of size, strength and density, which
      dominate under different coagulation conditions and govern cell removal, are not
      well understood. This paper investigated the floc properties produced during C-F
      of the cyanobacterium, Microcystis aeruginosa, under low and high doses of
      aluminium sulphate and ferric chloride coagulants and at different pH values, so
      as to promote charge neutralisation (CN) and sweep flocculation (SF) dominant
      conditions (or a combination of these). It was demonstrated that application of
      ferric chloride produced larger flocs that resulted in higher cell removal during
      jar testing. These flocs were also larger than those observed for natural organic
      matter (NOM) and kaolin, suggesting a role of algogenic organic matter (AOM) as
      an inherent bioflocculant. Under SF conditions, stronger flocs were produced;
      however, these had lower capacity for size recovery after exposure to high shear.
      Analysis of particle size distribution demonstrated that large scale
      fragmentation followed by erosion dominated for CN while erosion dominated under
      SF conditions. Overall, marked differences were observed dependent on the
      coagulation regime imposed that have implications for improving robustness of
      cell removal by downstream separation processes. While the cyanobacterium, M.
      aeruginosa, appeared to share general floc characteristics commonly observed for
      NOM and kaolin flocs, there were distinct differences in terms of size and
      strength, which may be attributed to AOM. 

PMID- 24859234
TI  - NK1 receptor blockade is ineffective in improving outcome following a balloon
      compression model of spinal cord injury.
AB  - The neuropeptide substance P (SP) is a well-known mediator of neurogenic
      inflammation following a variety of CNS disorders. Indeed, inhibition of SP
      through antagonism of its receptor, the tachykinin NK1 receptor, has been shown
      to be beneficial following both traumatic brain injury and stroke. Such studies
      demonstrated that administration of an NK1 receptor antagonist reduced blood
      brain-barrier permeability, edema development and improved functional outcome.
      Furthermore, our recent studies have demonstrated a potential role for SP in
      mediating neurogenic inflammation following traumatic spinal cord injury (SCI).
      Accordingly, the present study investigates whether inhibition of SP may
      similarly play a neuroprotective role following traumatic SCI. A closed balloon
      compression injury was induced at T10 in New Zealand White rabbits. At 30 minutes
      post-injury an NK1 receptor antagonist was administered intravenously. Animals
      were thereafter assessed for blood spinal cord barrier (BSCB) permeability,
      spinal water content (edema), intrathecal pressure (ITP), and histological and
      functional outcome from 5 hours to 2 weeks post-SCI. Administration of an NK1
      receptor antagonist was not effective in reducing BSCB permeability, edema, ITP,
      or functional deficits following SCI. We conclude that SP mediated neurogenic
      inflammation does not seem to play a major role in BSCB disruption, edema
      development and consequential tissue damage seen in acute traumatic SCI. Rather
      it is likely that the severe primary insult and subsequent hemorrhage may be the
      key contributing factors to ongoing SCI injury. 

PMID- 24859235
TI  - Enhanced expression of WD repeat-containing protein 35 via CaMKK/AMPK activation
      in bupivacaine-treated Neuro2a cells.
AB  - We previously reported that bupivacaine induces reactive oxygen species (ROS)
      generation, p38 mitogen-activated protein kinase (MAPK) activation and nuclear
      factor-kappa B activation, resulting in an increase in expression of WD repeat
      containing protein 35 (WDR35) in mouse neuroblastoma Neuro2a cells. However, the
      identity of signaling upstream of p38 MAPK pathways to WDR35 expression remains
      unclear. It has been shown that AMP-activated protein kinase (AMPK) can activate
      p38 MAPK through diverse mechanisms. In addition, several kinases acting upstream
      of AMPK have been identified including Ca2+/calmodulin-dependent protein kinase
      kinase (CaMKK). Recent studies reported that AMPK may be involved in bupivacaine
      induced cytotoxicity in Schwann cells and in human neuroblastoma SH-SY5Y cells.
      The present study was undertaken to test whether CaMKK and AMPK are involved in
      bupivacaine-induced WDR35 expression in Neuro2a cells. Our results showed that
      bupivacaine induced activation of AMPK and p38 MAPK in Neuro2a cells. The AMPK
      inhibitors, compound C and iodotubercidin, attenuated the bupivacaine-induced
      activation of AMPK and p38 MAPK, resulting in an inhibition of the bupivacaine
      induced increase in WDR35 expression. Treatment with the CaMKK inhibitor STO-609
      also attenuated the bupivacaine-induced activation of AMPK and p38 MAPK,
      resulting in an inhibition of the bupivacaine-induced increase in WDR35
      expression. These results suggest that bupivacaine activates AMPK and p38 MAPK
      via CaMKK in Neuro2a cells, and that the CaMKK/AMPK/p38 MAPK pathway is involved
      in regulating WDR35 expression. 

PMID- 24859237
TI  - Lying relies on the truth.
AB  - Cognitive models of deception focus on the conflict-inducing nature of the truth
      activation during lying. Here we tested the counterintuitive hypothesis that the
      truth can also serve a functional role in the act of lying. More specifically, we
      examined whether the construction of a lie can involve a two-step process, where
      the first step entails activating the truth, based upon which a lie response can
      be formulated in a second step. To investigate this hypothesis, we tried to
      capture the covert truth activation in a reaction-time based deception paradigm.
      Together with each question, we presented either the truth or lie response as
      distractors. If lying depends on the covert activation of the truth, deceptive
      responses would thus be facilitated by truth distractors relative to lie
      distractors. Our results indeed revealed such a "covert congruency" effect, both
      in errors and reaction times (Experiment 1). Moreover, stimulating participants
      to use the distractor information by increasing the proportion of truth
      distractor trials enlarged the "covert congruency" effects, and as such confirmed
      that the effects operate at a covert response level (Experiment 2). Our findings
      lend support to the idea that lying relies on a first step of truth telling, and
      call for a shift in theoretical thinking that highlights both the functional and
      interfering properties of the truth activation in the lying process. 

PMID- 24859236
TI  - CDC2 mediates progestin initiated endometrial stromal cell proliferation: a PR
      signaling to gene expression independently of its binding to chromatin.
AB  - Although non-genomic steroid receptor pathways have been studied over the past
      decade, little is known about the direct gene expression changes that take place
      as a consequence of their activation. Progesterone controls proliferation of rat
      endometrial stromal cells during the peri-implantation phase of pregnancy. We
      showed that picomolar concentration of progestin R5020 mimics this control in
      UIII endometrial stromal cells via ERK1-2 and AKT activation mediated by
      interaction of Progesterone Receptor (PR) with Estrogen Receptor beta (ERb) and
      without transcriptional activity of endogenous PR and ER. Here we identify early
      downstream targets of cytoplasmic PR signaling and their possible role in
      endometrial stromal cell proliferation. Microarray analysis of global gene
      expression changes in UIII cells treated for 45 min with progestin identified 97
      up- and 341 down-regulated genes. The most over-represented molecular functions
      were transcription factors and regulatory factors associated with cell
      proliferation and cell cycle, a large fraction of which were repressors down
      regulated by hormone. Further analysis verified that progestins regulate Ccnd1,
      JunD, Usf1, Gfi1, Cyr61, and Cdkn1b through PR-mediated activation of ligand-free
      ER, ERK1-2 or AKT, in the absence of genomic PR binding. ChIP experiments show
      that progestin promoted the interaction of USF1 with the proximal promoter of the
      Cdc2 gene. Usf1 knockdown abolished Cdc2 progestin-dependent transcriptional
      regulation and cell proliferation, which also blocked Cdc2 knockdown. We conclude
      that progestin-induced proliferation of endometrial stromal cells is mediated by
      ERK1-2 and AKT dependent early regulation of USF1, which directly induces Cdc2.
      To our knowledge, this is the first description of early target genes of
      progestin-activated classical PR via crosstalk with protein kinases and
      independently of hormone receptor binding to the genomic targets. 

PMID- 24859238
TI  - Generation of transgenic fibroblasts expressing pancreas-specific and doxycycline
      inducible ICER Igamma for the establishment of a porcine model of human diabetes
      mellitus.
AB  - Inducible cyclic AMP (cAMP) early repressor (ICER) Igamma acts as an endogenous
      inhibitor and disrupts the transcriptional regulation of cAMP response element
      binding protein (CREBP) responsive genes. Since the overexpression of ICER Igamma
      induces severe diabetes in a transgenic mouse model, with characteristics similar
      to human diabetes mellitus, an ICER Igamma construct containing an adjustable
      pancreas tissue specific promoter was utilized in the present study. Using the
      human insulin promoter region, a doxycycline (dox)-inducible ICER Igamma
      expression system was established using the tetracycline (tet)-controlled
      transactivator (tTA) with a TA response element (TRE) promoter. A unitary tet-on
      system that combined a tet-on activator cassette was also developed and was
      controlled by the human insulin promoter with a responder cassette containing
      genes encoding ICER Igamma regulated by the TRE promoter. To determine whether
      dox-enhanced ICER Igamma expression affected insulin production, the unitary tet
      on ICER Igamma vector was introduced into a mouse pancreatic beta-cell line and
      then the cells were treated with 0.1-1 mg/ml dox. The results revealed a robust
      increase in ICER Igamma expression and decreased insulin production. Therefore,
      this in vitro system may be useful for studying human diabetes mellitus and pre
      diabetes using tissue-specific promoters and a dox-inducible transgene. In
      addition, porcine transgenic fibroblasts containing dox-inducible ICER Igamma
      were generated. These fibroblasts may serve as a cell source for somatic cell
      nuclear transfer to generate a porcine model of human diabetes mellitus. 

PMID- 24859239
TI  - [Morphology of secondary ovarian tumors and metastases].
AB  - The distinction between primary and secondary (metastatic) ovarian tumors is
      essential for the selection of appropriate surgical interventions,
      chemotherapeutic treatment and prognostic evaluation for the patient. Metastatic
      tumors of the ovary range between 5 % and 30 %. The majority of ovarian
      metastases in Europe and North America derive from colorectal (25-50 %) and
      breast cancers (8-25 %). A major issue is the differential diagnosis of mucinous
      tumors. Major features favoring metastasis include bilaterality, size < 10 cm,
      ovarian surface involvement, extensive intra-abdominal spread, and infiltrative
      growth within the ovary involving the corpus albicans and corpora lutea. An
      algorithm using bilaterality and tumor size (cut-off 10 cm) allows correct
      categorization in approximately  85 % of the cases. Although immunohistochemistry
      (especially CK7 and CK20 in mucinous tumors) using a panel of antibodies plays a
      valuable role and is paramount in the diagnosis, the results must be interpreted
      with caution and within the relevant clinical and histopathological context. It
      is necessary to note that the correct diagnosis of ovarian metastases always
      needs interdisciplinary and multidisciplinary approaches. 

PMID- 24859241
TI  - Cost-effectiveness analysis of docetaxel versus weekly paclitaxel in adjuvant
      treatment of regional breast cancer in New Zealand.
AB  - BACKGROUND: There have been recent important changes to adjuvant regimens and
      costs of taxanes for the treatment of early breast cancer, requiring a re
      evaluation of comparative cost effectiveness. In particular, weekly paclitaxel is
      now commonly used but has not been subjected to cost-effectiveness analysis. AIM:
      Our aim was to estimate the cost effectiveness of adjuvant docetaxel and weekly
      paclitaxel versus each other, and compared with standard 3-weekly paclitaxel, in
      women aged >=25 years diagnosed with regional breast cancer in New Zealand.
      METHODS: A macrosimulation Markov model was used, with a lifetime horizon and
      health system perspective. The model compared 3-weekly docetaxel and weekly
      paclitaxel versus standard 3-weekly paclitaxel (E1199 regimen) in the hospital
      setting. Data on overall survival and toxicities (febrile neutropenia and
      peripheral neuropathy) were derived from relevant published clinical trials.
      Epidemiological and cost data were derived from New Zealand datasets. Health
      outcomes were measured with health-adjusted life-years (HALYs), similar to
      quality-adjusted life-years (QALYs). Costs included intervention and health
      system costs in year 2011 values, with 3% per annum discounting on costs and
      HALYs. RESULTS: The mean HALY gain per patient compared with standard 3-weekly
      paclitaxel was 0.51 with weekly paclitaxel and 0.21 with docetaxel, while
      incremental costs were $NZ 12,284 and $NZ 4,021, respectively. The incremental
      cost-effectiveness ratio (ICER) of docetaxel versus 3-weekly paclitaxel was $NZ
      19,400 (purchasing power parity [PPP]-adjusted $US 13,100) per HALY gained, and
      the ICER of weekly paclitaxel versus docetaxel was $NZ 27,100 ($US 18,300) per
      HALY gained. In terms of net monetary benefit, weekly paclitaxel was the optimal
      strategy for willingness-to-pay (WTP) thresholds >$NZ 27,000 per HALY gained.
      However, the model was highly sensitive to uncertainty around survival
      differences, while toxicity-related morbidity had little impact. Thus, if it was
      assumed that weekly paclitaxel and docetaxel had the same efficacy, docetaxel
      would be favoured over weekly paclitaxel. CONCLUSION: Both weekly paclitaxel and
      docetaxel are likely to be cost effective compared with standard 3-weekly
      paclitaxel. Weekly paclitaxel was the optimal choice for WTP thresholds greater
      than $NZ27,000 per HALY gained (PPP-adjusted $US 18,000). However, uncertainty
      remains around relative survival benefits, and weekly paclitaxel becomes cost
      ineffective versus docetaxel if it is assumed that the two regimens have equal
      effectiveness. Reduced uncertainty about the relative survival benefits may
      improve decision making for funding.

PMID- 24859240
TI  - Toxoplasma gondii and Neospora caninum seroprevalences in domestic South American
      camelids of the Peruvian Andes.
AB  - The objective of this study was to investigate the presence of Toxoplasma gondii-
      and Neospora caninum-specific antibodies in domestic South American camelids
      (SAC) (llamas and alpacas) from the Peruvian Andes through a cross-sectional
      study. A wide panel of serum samples collected from 1,845 llamas and 2,874
      alpacas from the two main SAC production areas of Peru was selected.
      Immunofluorescence antibody technique was employed to detect and titrate specific
      anti-T. gondii and anti-N. caninum immunoglobulins G in serum samples. The
      association between T. gondii and N. caninum seroprevalence and the geographical
      origin (Central and South Peruvian Andes) was evaluated. Anti-T. gondii
      antibodies were found in 460 (24.9 %) llamas and 706 (24.6 %) alpacas, whereas
      anti-N. caninum antibodies were detected in 153 (8.3 %) llamas and 425 (14.8 %)
      alpacas. Toxoplasma gondii infection was strongly associated with the South
      Peruvian Andes where moderate climate conditions, larger human population,
      compared to the Central region, and the presence of wildlife definitive hosts
      could favor horizontal transmission to SAC. In contrast, N. caninum infection was
      not associated with the geographical region. These results indicate that T.
      gondii and N. caninum infections are highly and moderately widespread,
      respectively, in both species of domestic SAC studied in the sampled areas and
      appropriate control measures should be undertaken to reduce the prevalence of
      both parasitic infections. 

PMID- 24859242
TI  - Do changes in drug coverage policy point to an increased role for cost
      effectiveness analysis in the USA?
AB  - Compared with other countries, cost-effectiveness analysis has traditionally had
      a limited role in US health care. Rather, US payers have typically accommodated
      the introduction of expensive technology by passing an increasing proportion of
      costs to patients, through raising insurance premiums and/or by increasing
      copayments, coinsurance, and deductibles. However, in what may prove to be a
      tipping point, the two largest pharmacy benefit managers have chosen to exclude
      drugs from their formularies that offer uncertain health benefit compared with
      cheaper alternatives. This paper argues that cost-effectiveness analysis should
      be used to inform these value-based decisions, and that by using information
      other than robust cost-effectiveness evidence, payers risk wrongly denying
      beneficiaries access to important medical technologies. If cost-effectiveness
      analysis were to be used in this way, it would be another in a growing number of
      examples of its use across public and private payers. In the absence of a
      centralized agency conducting cost-effectiveness analysis, the recently
      inaugurated 2nd Panel on Cost-Effectiveness in Health and Medicine has an
      important role to play in standardizing methods and promoting best practice. 

PMID- 24859243
TI  - Effect of deoxynivalenol and other Type B trichothecenes on the intestine: a
      review.
AB  - The natural food contaminants, mycotoxins, are regarded as an important risk
      factor for human and animal health, as up to 25% of the world's crop production
      may be contaminated. The Fusarium genus produces large quantities of
      fusariotoxins, among which the trichothecenes are considered as a ubiquitous
      problem worldwide. The gastrointestinal tract is the first physiological barrier
      against food contaminants, as well as the first target for these toxicants. An
      increasing number of studies suggest that intestinal epithelial cells are targets
      for deoxynivalenol (DON) and other Type B trichothecenes (TCTB). In humans,
      various adverse digestive symptoms are observed on acute exposure, and in
      animals, these toxins induce pathological lesions, including necrosis of the
      intestinal epithelium. They affect the integrity of the intestinal epithelium
      through alterations in cell morphology and differentiation and in the barrier
      function. Moreover, DON and TCTB modulate the activity of intestinal epithelium
      in its role in immune responsiveness. TCTB affect cytokine production by
      intestinal or immune cells and are supposed to interfere with the cross-talk
      between epithelial cells and other intestinal immune cells. This review
      summarizes our current knowledge of the effects of DON and other TCTB on the
      intestine. 

PMID- 24859247
TI  - New tool advances investigations of disease outbreaks.

PMID- 24859246
TI  - Interspecific variation in Rx1 expression controls opsin expression and causes
      visual system diversity in African cichlid fishes.
AB  - The mechanisms underlying natural phenotypic diversity are key to understanding
      evolution and speciation. Cichlid fishes are among the most speciose vertebrates
      and an ideal model for identifying genes controlling species differences.
      Cichlids have diverse visual sensitivities that result from species expressing
      subsets of seven cichlid cone opsin genes. We previously identified a
      quantitative trait locus (QTL) that tunes visual sensitivity by varying SWS2A
      (short wavelength sensitive 2A) opsin expression in a genetic cross between two
      Lake Malawi cichlid species. Here, we identify Rx1 (retinal and anterior neural
      fold homeobox) as the causative gene for the QTL using fine mapping and RNAseq in
      retinal transcriptomes. Rx1 is differentially expressed between the parental
      species and correlated with SWS2A expression in the F2 progeny. Expression of Rx1
      and SWS2A is also correlated in a panel of 16 Lake Malawi cichlid species.
      Association mapping in this panel identified a 413-bp deletion located 2.5-kb
      upstream of the Rx1 translation start site that is correlated with decreased Rx1
      expression. This deletion explains 62% of the variance in SWS2A expression across
      53 cichlid species in 29 genera. The deletion occurs in both the sand and rock
      dwelling cichlid clades, suggesting that it is an ancestral polymorphism. Our
      finding supports the hypothesis that mixing and matching of ancestral
      polymorphisms can explain the diversity of present day cichlid phenotypes. 

PMID- 24859245
TI  - An experimentally determined evolutionary model dramatically improves
      phylogenetic fit.
AB  - All modern approaches to molecular phylogenetics require a quantitative model for
      how genes evolve. Unfortunately, existing evolutionary models do not
      realistically represent the site-heterogeneous selection that governs actual
      sequence change. Attempts to remedy this problem have involved augmenting these
      models with a burgeoning number of free parameters. Here, I demonstrate an
      alternative: Experimental determination of a parameter-free evolutionary model
      via mutagenesis, functional selection, and deep sequencing. Using this strategy,
      I create an evolutionary model for influenza nucleoprotein that describes the
      gene phylogeny far better than existing models with dozens or even hundreds of
      free parameters. Emerging high-throughput experimental strategies such as the one
      employed here provide fundamentally new information that has the potential to
      transform the sensitivity of phylogenetic and genetic analyses. 

PMID- 24859244
TI  - Diagnosis of snakebite and the importance of immunological tests in venom
      research.
AB  - In many cases of envenoming following snake bite, the snake responsible for the
      accident remains unidentified; this frequently results in difficulty deciding
      which antivenom to administer to the systemically-envenomed victim, especially
      when only monospecific antivenoms are available. Normally the specific diagnosis
      of snake bite can be conveniently made using clinical and laboratory methods.
      Where clinical diagnosis depends upon the recognition of specific signs of
      envenoming in the patient, laboratory diagnosis is based on the changes which
      occur in envenomed victims including the detection of abnormalities in blood
      parameters, presence/absence of myoglobinuria, changes in certain enzyme levels,
      presence/absence of neurotoxic signs and the detection in the blood of specific
      venom antigens using immunologically-based techniques, such as enzyme
      immunoassay. It is the latter which is the main subject of this review, together
      with the application of techniques currently used to objectively assess the
      effectiveness of new and existing antivenoms, to assess first aid measures, to
      investigate the possible use of such methods in epidemiological studies, and to
      detect individual venom components. With this in mind, we have discussed in some
      detail how such techniques were developed and how they have helped in the
      treatment of envenoming particularly and in venom research in general. 

PMID- 24859248
TI  - New analysis of seven ant genomes reveals clues to longer life spans associated
      with sociality.

PMID- 24859249
TI  - Scientists reveal new picture in the evolution of flightless birds.

PMID- 24859250
TI  - A pro-atherogenic HDL profile in coronary heart disease patients: an iTRAQ
      labelling-based proteomic approach.
AB  - OBJECTIVES: This study aims to compare the protein composition of high-density
      lipoprotein (HDL) particles in coronary heart disease (CHD) patients and controls
      by proteomic methods. BACKGROUND: HDL has been reported to exert pro-atherogenic
      properties in CHD patients. Accumulating evidence indicates that HDL composition,
      rather than the HDL-C level, determines its functions. The changes in HDL
      composition involved in the conversion of anti-atherogenic to pro-atherogenic
      properties in CHD patients are currently unknown. METHODS AND RESULTS: iTRAQ
      combined with nanoLC-MS/MS was performed to obtain a differential expression
      profile of the HDL pooled samples of the male age-matched CHD patients and
      controls (n = 10/group). Of the 196 proteins identified in the examined HDL, 12
      were differentially expressed between the CHD patients and the controls,
      including five up-regulated proteins and seven down-regulated proteins. Using GO
      analysis, we determined that the up-regulated proteins were mostly involved in
      inflammatory reactions, displaying a potential pro-atherogenic profile. In
      contrast, the down-regulated proteins were mostly involved in lipid metabolism
      processes, displaying anti-atherogenic properties. To confirm the proteomic
      results, serum amyloid A (SAA) and apoC-I were selected and quantified by ELISA,
      in the same population as the proteomic analysis, as well as another independent
      population (n = 120/group). Consistent with the proteomic results, the amount of
      SAA was significantly increased, and apoC-I was significantly decreased in the
      HDL particles of CHD patients compared with those of controls (P<0.05).
      CONCLUSIONS: Our study shows that the HDL proteome changes to a pro-atherogenic
      profile in CHD patients, which might compromise the protective effects of HDL.
      Proteomic analysis of HDL composition may provide more relevant information
      regarding their functional properties than steady-state HDL-C levels.

PMID- 24859251
TI  - Evoked temporal summation in cats to highlight central sensitization related to
      osteoarthritis-associated chronic pain: a preliminary study.
AB  - In cats, osteoarthritis causes significant chronic pain. Chronicity of pain is
      associated with changes in the central nervous system related to central
      sensitization, which have to be quantified. Our objectives were 1) to develop a
      quantitative sensory testing device in cats for applying repetitive mechanical
      stimuli that would evoke temporal summation; 2) to determine the sensitivity of
      this test to osteoarthritis-associated pain, and 3) to examine the possible
      correlation between the quantitative sensory testing and assessment using other
      pain evaluation methods. We hypothesized that mechanical sub-threshold repetitive
      stimuli would evoke temporal summation, and that cats with osteoarthritis would
      show a faster response. A blinded longitudinal study was performed in 4 non
      osteoarthritis cats and 10 cats with naturally occurring osteoarthritis.
      Quantification of chronic osteoarthritis pain-related disability was performed
      over a two week period using peak vertical force kinetic measurement, motor
      activity intensity assessment and von Frey anesthesiometer-induced paw withdrawal
      threshold testing. The cats afflicted with osteoarthritis demonstrated
      characteristic findings consistent with osteoarthritis-associated chronic pain.
      After a 14-day acclimation period, repetitive mechanical sub-threshold stimuli
      were applied using a purpose-developed device. Four stimulation profiles of
      predetermined intensity, duration and time interval were applied randomly four
      times during a four-day period. The stimulation profiles were different
      (P<0.001): the higher the intensity of the stimulus, the sooner it produced a
      consistent painful response. The cats afflicted with osteoarthritis responded
      more rapidly than cats osteoarthritis free (P = 0.019). There was a positive
      correlation between the von Frey anesthesiometer-induced paw withdrawal threshold
      and the response to stimulation profiles #2 (2N/0.4 Hz) and #4 (2N/0.4 Hz): Rhos
      = 0.64 (P = 0.01) and 0.63 (P = 0.02) respectively. This study is the first
      report of mechanical temporal summation in awake cats. Our results suggest that
      central sensitization develops in cats with naturally occurring osteoarthritis,
      providing an opportunity to improve translational research in osteoarthritis
      associated chronic pain. 

PMID- 24859252
TI  - Effects of different colors of light on melatonin suppression and expression
      analysis of Aanat1 and melanopsin in the eye of a tropical damselfish.
AB  - Ocular melatonin production exhibits a daily rhythm with a decrease during
      photophase and an increase during scotophase (nocturnal pattern) in teleost fish
      due to day-night changes in the activity of the rate-limiting melatonin
      synthesizing enzyme arylalkylamine N-acetyltransferase (AANAT). Acute light
      exposure during scotophase suppresses AANAT activity and melatonin production in
      the eyes, suggesting that external light signals are a principal regulator of
      ocular melatonin synthesis. To better understand the photic regulation of ocular
      melatonin synthesis in teleost fish, this study sought to characterize the effect
      of light on ocular melatonin synthesis in the sapphire devil Chrysiptera cyanea,
      which shows a nocturnal pattern and light-induced inhibition of ocular melatonin
      production during scotophase. Exposure to three different wavelengths of light
      (half-peak bandwidth=435-475 nm with a peak of 455 nm, 495-565 nm with a peak of
      530 nm, and 607-647 nm with a peak of 627 nm for the blue, green, and red LEDs)
      for 2h during scotophase resulted in the blue wavelength significantly decreasing
      ocular melatonin content within 30 min after light exposure. This result clearly
      indicates that the effective range of visible light on ocular melatonin
      suppression is distributed within the wavelengths of blue light and that a blue
      light-sensitive opsin is involved in ocular melatonin suppression in the fish. A
      PCR-based cloning method revealed the expression of melanopsin, a putative blue
      light-sensitive nonvisual opsin, in the eyes. Furthermore, in situ hybridization
      using the sapphire devil Aanat1 and melanopsin RNA probes showed mRNA expressions
      of both genes in the inner nuclear and ganglion cell layer of the fish retina.
      These results suggest that melanopsin is a possible candidate photoreceptor
      involved in ocular melatonin suppression by an external light signal in the
      sapphire devil.

PMID- 24859253
TI  - Long-term GnRH-induced gonadotropin secretion in a novel hypothalamo-pituitary
      slice culture from tilapia brain.
AB  - Organotypic cultures, prepared from hypothalamo-pituitary slices of tilapia, were
      developed to enable long-term study of secretory cells in the pituitary of a
      teleost. Values of membrane potential at rest were similar to those recorded from
      acute slices, and cells presented similar spontaneous spikes and spikelets. Some
      cells also exhibited slow spontaneous oscillations in membrane potential, which
      may be network-driven. Long-term (6days) continuous exposure to GnRH induced
      increases in LH and FSH secretion. FSH levels reached the highest levels after
      24h of exposure to GnRH, and the highest secretion of LH was observed in days 4
      and 5 of the experiment. Since slices were viable for several weeks in culture,
      maintaining the original cytoarchitecture, electrical membrane properties and the
      ability to secrete hormones in response to exogenous GnRH, this technique is
      ideal for studying the mechanisms regulating cell-to-cell communication under
      conditions resembling the in vivo tissue organization. 

PMID- 24859254
TI  - Expression and regulation of avian cathepsin L in the oviduct during molting.
AB  - Cathepsins (CTSs) are peptidases that have biological roles in degrading
      extracellular matrix, catabolism of intracellular proteins, and processing of pro
      hormones. Of these, cathepsin L (CTSL) is closely associated with morphological
      changes in reproductive organs required for proper function in mammals, including
      humans and mice, but little is known about CTSL in avian species. In the present
      study, the expression of CTSL was investigated in the oviduct of hens during
      regression and recrudescence in response to molting. Our results revealed that
      expression of CTSL mRNA increased (P<0.001) when the oviduct underwent regression
      during the molting period in hens. In situ hybridization and immunohistochemial
      analyses detected CTSL mRNA and protein predominantly in the luminal (LE) and
      glandular epithelia (GE) during regression of the oviduct, but not during
      regeneration of the oviduct. Expression of CTSL decreased in the oviduct of
      chicks treated with diethylstilbestrol (DES, a synthetic estrogen agonist).
      Furthermore, we discovered four miRNAs including miR-23b, miR-551, miR-1464 and
      miR-1803 that regulate expression of the CTSL gene at the post-transcriptional
      level, which suggests that CTSL mRNA can be regulated by specific miRNAs via 3'
      UTR in chickens. Results of the present research suggest that estrogen regulates
      expression of CTSL during regression of the oviduct during molting and that down
      regulation of CTSL is likely a prerequisite for the normal regeneration of
      oviductal tissues following molting in laying hens. 

PMID- 24859255
TI  - Response of testosterone and corticosterone plasma levels to the challenge of
      sibling competition: a study in common terns.
AB  - The hormonal response to social challenges has been widely studied, however, most
      work focused on adult behavior in a reproductive context although developing
      animals also encounter important social challenges early in life. We studied the
      relationship between acute sibling competition and plasma corticosterone (CORT)
      and testosterone (T) in common tern (Sterna hirundo) chicks, a species whose
      young compete for access to food by scramble interactions. Blood samples were
      taken in nests with two and only one single chick both immediately after a
      feeding bout and in non-challenged controls. We found that T levels were lower in
      siblings challenged by a feeding bout as compared to controls, which may be
      explained by the fact that T suppresses begging behavior and is only elevated in
      response to territorial intrusion but not sibling competition in a related
      species. Singletons had, corrected for body condition, generally lower CORT
      levels than siblings suggesting that growing up with siblings creates a
      competitive environment in which high CORT levels are sustained irrespective of a
      social challenge. CORT levels were also negatively correlated with body condition
      and were higher in males than in females. The latter may be related to sex
      specific food requirements and susceptibility to stress. Our results suggest a
      possible suppressive effect of acute sibling competition on T secretion, and a
      positive effect on CORT levels by longer term sibling competition. The degree to
      which these dynamics are related to begging or aggression, or both, needs further
      experimental work. 

PMID- 24859256
TI  - Evolutionary history of the neuropeptide S receptor/neuropeptide S system.
AB  - The neuropeptide S receptor (NPSR) belongs to the G protein-coupled receptor
      (GPCR) superfamily and is activated by the neuropeptide S (NPS). Although
      recently discovered, the vertebrate NPSR-NPS system has been established as an
      important signaling system in the central nervous system and is involved in
      physiological processes such as locomotor activity, wakefulness, asthma
      pathogenesis, anxiety and food intake. The availability of a large number of
      genome sequences from multiple bilaterian lineages has provided an opportunity to
      establish the evolutionary history of the system. This review describes the
      origin and the molecular evolution of the NPSR-NPS system using data derived
      primarily from comparative genomic analyses. These analyses indicate that the
      NPSR-NPS system and the vasopressin-like receptor-vasopressin/oxytocin peptide
      (VPR-VP/OT) system originated from a single system in an ancestral bilaterian.
      Multiple duplications of this ancestral system gave rise to the bilaterian VPR
      VP/OT system and to the protostomian cardioacceleratory peptide receptor
      cardioacceleratory peptide (CCAPR-CCAP) system and to the NPSR-NPS system in the
      deuterostomes. Gene structure features of the receptors were consistent with the
      orthology annotations derived from phylogenetic analyses. The orthology of the
      peptide precursors closely paralleled that of the receptors suggesting an ancient
      coevolution of the receptor-peptide pair. An important challenge for the
      coevolution hypothesis will be to establish the molecular and structural basis of
      the divergence between orthologous receptor-ligand pairs in this system. 

PMID- 24859257
TI  - Social regulation of reproduction in male cichlid fishes.
AB  - Social interactions and relative positions within a dominance hierarchy have
      helped shape the evolution of reproduction in many animals. Since reproduction is
      crucial in all animals, and rank typically regulates access to reproductive
      opportunities, understanding the mechanisms that regulate socially-induced
      reproductive processes is extremely important. How does position in a dominance
      hierarchy impact an individual's reproductive behavior, morphology, and
      physiology? Teleost fishes, and cichlids in particular, are ideally-suited models
      for studying how social status influences reproduction on multiple levels of
      biological organization. Here I review the current knowledge on the reproductive
      behavioral and physiological consequences of relative position in a dominance
      hierarchy, with a particular focus on male cichlids. Dominant and subordinate
      social status is typically associated with distinct differences in activity along
      the entire hypothalamic-pituitary-gonadal axis. Further, when transitions in
      social status occur between subordinate and dominant individuals, there are
      plastic changes from whole-organism behavior to molecular-level gene expression
      modifications that occur quickly. These rapid changes in behavior and physiology
      have allowed cichlids the flexibility to adapt to and thrive in their often
      dynamic physical and social environments. Studies in cichlid fishes have, and
      will continue, to advance our understanding of how the social environment can
      modulate molecular, cellular, and behavioral outcomes relevant to reproductive
      success. Future studies that take advantage of the extreme diversity in mating
      systems, reproductive tactics, and parental care strategies within the cichlid
      group will help generate hypotheses and careful experimental tests on the
      mechanisms governing the social control of reproduction in many vertebrates. 

PMID- 24859258
TI  - Genes encoding aromatases in teleosts: evolution and expression regulation.
AB  - Cytochrome P450 aromatases, encoded by cyp19a1 genes, catalyzes the conversion of
      androgens to estrogens and plays important roles in the reproduction of
      vertebrates. Vertebrate cyp19a1 genes showed high synteny in chromosomal
      locations and conservation in sequences during evolution. However, amphioxus
      cyp19a1 does not show synteny to vertebrate cyp19a1. Teleost fish possess two
      copies of the cyp19a1 gene, which were postulated to result from a fish-specific
      genome duplication. The duplicated copies of fish cyp19a1 genes evolved into the
      brain and ovarian forms of cytochrome P450 aromatase genes, cyp19a1a and
      cyp19a1b, respectively, with different regulatory mechanisms of expression,
      through subfunctionalization under long-term selective pressure. In addition to
      the estradiol (E2) auto-regulatory loop, there may be other mechanisms
      responsible for the high expression of aromatase in the teleost brain. The study
      of the two cyp19a1 copies in teleost fish will shed light on the general
      evolution, function, and regulation of vertebrate cyp19a1. 

PMID- 24859259
TI  - Expression and localization of gonadotropic hormone subunits (Gpa, Fshb, and Lhb)
      in the pituitary during gonadal differentiation in medaka.
AB  - To clarify the appearance of and chronological changes in two different
      gonadotropic hormone (Gth) cells, we examined the dynamics of Gth cells in detail
      during gonadal differentiation and development in the d-rR strain of medaka
      (Oryzias latipes). Expression of the sex-determining gene Dmy was evident in
      gonadal somatic cells at 5 days post-fertilization (dpf). Glycoprotein-alpha
      (Gpa)-positive cells first appeared in the pituitary at 4 dpf, regardless of
      genetic sex, while follicle-stimulating hormone-beta (Fshb)-positive cells was
      detected in XX and XY embryos at 5 and 6 dpf, respectively. In contrast,
      luteinizing hormone-beta (Lhb)-positive cells were observed in both sexes of
      medaka after 70 days post-hatching (dph). The density of Fshb-positive cells in
      the pituitary was significantly and transiently higher in XX than in XY fry at 0
      dph, and thereafter no significant differences were detected before sexual
      maturation. In this study, temporal expression of Fshb was observed, indicating
      that Fsh cells become differentiated before hatching and that sexual dimorphism
      in Fsh cells occurs transiently after sex determination in medaka.

PMID- 24859260
TI  - Surgical management of functional bladder outlet obstruction in adults with
      neurogenic bladder dysfunction.
AB  - BACKGROUND: The most common type of functional bladder outlet obstruction in
      patients with neurogenic bladder is detrusor-sphincter dyssynergia (DSD). The
      lack of co-ordination between the bladder and the external urethral sphincter
      muscle (EUS) in DSD can result in poor bladder emptying and high bladder
      pressures, which may eventually lead to progressive renal damage. OBJECTIVES: To
      assess the effectiveness of different surgical therapies for the treatment of
      functional bladder outlet obstruction (i.e. DSD) in adults with neurogenic
      bladder dysfunction. SEARCH METHODS: We searched the Cochrane Incontinence Group
      Specialised Register, which contains trials identified from the Cochrane Central
      Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE In-Process, and
      handsearching of journals and conference proceedings (searched 20 February 2014),
      and the reference lists of relevant articles. SELECTION CRITERIA: Randomised
      controlled trials (RCTs) or quasi-RCTs comparing a surgical treatment of DSD in
      adults suffering from neurogenic bladder dysfunction, with no treatment, placebo,
      non-surgical treatment, or other surgical treatment, alone or in combination.
      DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial
      quality and extracted data. MAIN RESULTS: We included five trials (total of 199
      participants, average age of 40 years). The neurological diseases causing DSD
      were traumatic spinal cord injury (SCI), multiple sclerosis (MS), or congenital
      malformations.One trial compared placement of sphincteric stent prosthesis with
      sphincterotomy. For urodynamic measurements, results for postvoid residual urine
      volume (PVR) and cystometric bladder capacity were inconclusive and consistent
      with benefit of either sphincteric stent prosthesis or sphincterotomy at three,
      six, 12, and 24 months. Results for maximum detrusor pressure (Pdet.max) were
      also inconclusive at three, six, and 12 months; however, after two years, the
      Pdet.max after sphincterotomy was lower than after stent placement (mean
      difference (MD) -30 cmH2O, 95% confidence interval (CI) 8.99 to 51.01).Four
      trials considered botulinum A toxin (BTX-A) injection in the EUS, either alone or
      in combination with other treatments. The comparators included oral baclofen,
      oral alpha blocker, lidocaine, and placebo. The BTX-A trials all differed in
      protocols, and therefore we did not undertake meta-analysis. A single 100 units
      transperineal BTX-A injection (Botox(r)) in patients with MS resulted in higher
      voided urine volumes (MD 69 mL, 95% CI 11.87 to 126.13), lower pre-micturition
      detrusor pressure (MD -10 cmH2O, 95% CI -17.62 to -2.38), and lower Pdet.max (MD 
      14 cmH2O, 95% CI -25.32 to -2.68) after 30 days, compared to placebo injection.
      Results for PVR using catheterisation, basal detrusor pressure, maximal bladder
      capacity, maximal urinary flow, bladder compliance at functional bladder
      capacity, maximal urethral pressure, and closure urethral pressure at 30 days
      were inconclusive and consistent with benefit of either BTX-A injection or
      placebo injections. In participants with SCI, treatment with 200 units of Chinese
      manufactured BTX-A injected at eight different sites resulted in better bladder
      compliance (MD 7.5 mL/cmH2O, 95% CI -10.74 to -4.26) than participants who
      received the same injections with the addition of oral baclofen. Results for
      maximum uroflow rate, maximal cystometric capacity, and volume per voiding were
      inconclusive and consistent with benefit of either BTX-A injection or BTX-A
      injection with the addition of oral baclofen. However, the poor quality of
      reporting in this trial caused us to question the relevance of bladder compliance
      as an adequate outcome measure.In participants with DSD due to traumatic SCI, MS,
      or congenital malformation, the results for PVRs after one day were inconclusive
      and consistent with benefit of either a single 100 units transperineal BTX-A
      (Botox(r)) injection or lidocaine injection. However, after seven and 30 days of
      BTX-A injection, PVRs were lower (MD -163 and -158 mL, 95% CI -308.65 to -17.35
      and 95% CI -277.57 to -39.03, respectively) compared to participants who received
      lidocaine injections. Results at one month for Pdet.max on voiding, EUS activity
      in electromyography, and maximal urethral pressure were inconclusive and
      consistent with benefit of either BTX-A or lidocaine injections.Finally, one
      small trial consisting of five men with SCI compared weekly BTX-A injections with
      normal saline as placebo. The placebo had no effect on DSD in the two
      participants allocated to the placebo treatment. Their urodynamic parameters were
      unchanged from baseline values until subsequent injections with BTX-A once a week
      for three weeks. These subsequent injections resulted in similar responses to
      those of the three participants who were allocated to the BTX-A treatment.
      Unfortunately, the report presented no data on placebo treatment.Only the trial
      that compared sphincterotomy with stent placement reported outcome measures renal
      function and urologic complications related to DSD. Results for renal function at
      12 and 24 months, and urologic complications related to DSD at three, six, 12,
      and 24 months were inconclusive and consistent with benefit of either sphincteric
      stent prosthesis or sphincterotomy.Adverse effects reported were haematuria due
      to the cystoscopic injection and muscle weakness, of which the latter may be
      related to the BTX-A dose used.All trials had some methodological shortcomings,
      so insufficient information was available to permit judgement of risk of bias. At
      least half of the trials had an unclear risk of selection bias and reporting
      bias. One trial had a high risk of attrition bias, and another trial had a high
      risk of reporting bias. AUTHORS' CONCLUSIONS: Results from small studies with a
      high risk of bias have identified evidence of limited quality that intraurethral
      BTX-A injections improve some urodynamic measures after 30 days in the treatment
      of functional bladder outlet obstruction in adults with neurogenic bladder
      dysfunction. The necessity of reinjection of BTX-A is a significant drawback; a
      sphincterotomy might therefore be a more effective treatment option for lowering
      bladder pressure in the long-term.However, because of the limited availability of
      eligible trials, this review was unable to provide robust evidence in favour of
      any of the surgical treatment options. More RCTs are needed, measuring
      improvement on quality of life, and on other types of surgical treatment options
      for DSD since these are lacking. Future RCTs assessing the effectiveness of BTX-A
      injections also need to address the uncertainty about the optimal dose and mode
      of injection for this specific type of urological condition.

PMID- 24859261
TI  - Alterations in auxin homeostasis suppress defects in cell wall function.
AB  - The plant cell wall is a highly dynamic structure that changes in response to
      both environmental and developmental cues. It plays important roles throughout
      plant growth and development in determining the orientation and extent of cell
      expansion, providing structural support and acting as a barrier to pathogens.
      Despite the importance of the cell wall, the signaling pathways regulating its
      function are not well understood. Two partially redundant leucine-rich-repeat
      receptor-like kinases (LRR-RLKs), FEI1 and FEI2, regulate cell wall function in
      Arabidopsis thaliana roots; disruption of the FEIs results in short, swollen
      roots as a result of decreased cellulose synthesis. We screened for suppressors
      of this swollen root phenotype and identified two mutations in the putative
      mitochondrial pyruvate dehydrogenase E1alpha homolog, IAA-Alanine Resistant 4
      (IAR4). Mutations in IAR4 were shown previously to disrupt auxin homeostasis and
      lead to reduced auxin function. We show that mutations in IAR4 suppress a subset
      of the fei1 fei2 phenotypes. Consistent with the hypothesis that the suppression
      of fei1 fei2 by iar4 is the result of reduced auxin function, disruption of the
      WEI8 and TAR2 genes, which decreases auxin biosynthesis, also suppresses fei1
      fei2. In addition, iar4 suppresses the root swelling and accumulation of ectopic
      lignin phenotypes of other cell wall mutants, including procuste and cobra.
      Further, iar4 mutants display decreased sensitivity to the cellulose biosynthesis
      inhibitor isoxaben. These results establish a role for IAR4 in the regulation of
      cell wall function and provide evidence of crosstalk between the cell wall and
      auxin during cell expansion in the root. 

PMID- 24859263
TI  - Provision of deep procedural sedation by a pediatric sedation team at a
      freestanding imaging center.
AB  - BACKGROUND: Freestanding imaging centers are popular options for health care
      systems to offer services accessible to local communities. The provision of deep
      sedation at these centers could allow for flexibility in scheduling imaging for
      pediatric patients. Our Children's Sedation Services group, comprised of
      pediatric critical care medicine and pediatric emergency medicine physicians, has
      supplied such a service for 5 years. However, limited description of such off
      site services exists. The site has resuscitation equipment and medications, yet
      limited staffing and no proximity to hospital support. OBJECTIVE: To describe the
      experience of a cohort of pediatric patients undergoing sedation at a
      freestanding imaging center. MATERIALS AND METHODS: A retrospective chart review
      of all sedations from January 2012 to December 2012. Study variables include
      general demographics, length of sedation, type of imaging, medications used,
      completion of imaging, adverse events based on those defined by the Pediatric
      Sedation Research Consortium database and need for transfer to a hospital for
      additional care. RESULTS: Six hundred fifty-four consecutive sedations were
      analyzed. Most patients were low acuity American Society of Anesthesiologists
      physical class <= 2 (91.8%). Mean sedation time was 55 min (SD +/- 24). The
      overwhelming majority of patients (95.7%) were sedated for MRI, 3.8% for CT and
      <1% (three patients) for both modalities. Propofol was used in 98% of cases.
      Overall, 267 events requiring intervention occurred in 164 patient encounters
      (25.1%). However, after adjustment for changes from expected physiological
      response to the sedative, the rate of events was 10.2%. Seventy-five (11.5%)
      patients had desaturation requiring supplemental oxygen, nasopharyngeal tube or
      oral airway placement, continuous positive airway pressure or brief bag valve
      mask ventilation. Eleven (1.7%) had apnea requiring continuous positive airway
      pressure or bag valve mask ventilation briefly. One patient had bradycardia that
      resolved with nasopharyngeal tube placement and continuous positive airway
      pressure. Fifteen (2.3%) patients had hypotension requiring adjustment of the
      sedation drip but no fluid bolus. Overall, there were six failed sedations
      (0.9%), defined by the inability to complete the imaging study. There were no
      serious adverse events. There were no episodes of cardiac arrest or need for
      intubation. No patient required transfer to a hospital. CONCLUSION: Sedation
      provided at this freestanding imaging center resulted in no serious adverse
      events and few failed sedations. While this represents a limited cohort with
      sedations performed by predominately pediatric critical care medicine and
      pediatric emergency medicine physicians, these findings have implications for the
      design and potential scope of practice of outpatient pediatric sedation services
      to support community-based pediatric imaging.

PMID- 24859262
TI  - Elf5 counteracts precocious trophoblast differentiation by maintaining Sox2 and 3
      and inhibiting Hand1 expression.
AB  - In mice the transcription factor Elf5 is necessary for correct trophoblast
      development. Upon knockdown of Elf5, TS cells display neither a decrease in
      proliferation nor an increase in cell death but rather an increased propensity to
      differentiate. Such cells rapidly lose Sox2 and 3 expression, while transiently
      upregulating the giant cell differentiation determinant gene Hand1. Other genes
      affected within 24h of Elf5 knock-down, many of which have not previously been
      implicated in trophoblast development, exhibited in vivo expression domains and
      in vitro expression responses consistent with Elf5 having a role in counteracting
      trophoblast differentiation. In an ES to TS differentiation assay using Cdx2
      overexpression with Elf5 loss of function cell lines, it was shown that Elf5 is
      necessary to prevent terminal trophoblast differentiation. This data thus suggest
      that Elf5 is a gatekeeper for the TS to differentiated trophoblast transition
      thereby preventing the precocious differentiation of the undifferentiated
      extraembryonic ectoderm. 

PMID- 24859264
TI  - Prediction of compliance with MRI procedures among children of ages 3 years to 12
      years.
AB  - BACKGROUND: A number of children are unable to comply with an MRI procedure and
      require general anesthetic. However, we lack information about which factors are
      associated with MRI compliance in young children. OBJECTIVE: To determine the
      strongest predictors of MRI compliance, focusing on variables that can be easily
      rated by patients' parents. MATERIALS AND METHODS: A sample of 205 children ages
      3-11 years (mean age 6.6 years) who were at risk of non-compliance were recruited
      from a children's hospital. Their parents completed a behavior assessment scale
      for children as well as a questionnaire that assessed their expectations of
      compliance and perception of their child's typical medical compliance. The
      children subsequently completed a mock MRI with an educational play therapist and
      a clinical MRI, with the quality of the scan scored by the MRI technologist.
      RESULTS: Overall, 88.3% of children complied with the clinical scan and achieved
      diagnostic images, with age unrelated to compliance in this well-prepared patient
      group. The strongest predictors of MRI compliance were parental expectations and
      ratings of how well the child typically copes with medical procedures. Non
      compliance was related to child attention problems and to poor adaptability among
      children. A total of 64 preschool-age children (91.4%) and 110 school-age
      children (95.7%) were correctly classified as compliant or non-compliant based on
      these predictor variables. CONCLUSION: A child's temperament, medical experiences
      and parental expectations provide important information in predicting which
      children successfully comply with an MRI procedure and which require general
      anesthesia. Further study is needed to explore the utility of these variables in
      predicting compliance at sites that do not have access to an MRI simulator.

PMID- 24859265
TI  - The contribution of geography to disparities in preventable hospitalisations
      between indigenous and non-indigenous Australians.
AB  - OBJECTIVES: To quantify the independent roles of geography and Indigenous status
      in explaining disparities in Potentially Preventable Hospital (PPH) admissions
      between Indigenous and non-Indigenous Australians. DESIGN, SETTING AND
      PARTICIPANTS: Analysis of linked hospital admission data for New South Wales
      (NSW), Australia, for the period July 1 2003 to June 30 2008. MAIN OUTCOME
      MEASURES: Age-standardised admission rates, and rate ratios adjusted for age, sex
      and Statistical Local Area (SLA) of residence using multilevel models. RESULTS:
      PPH diagnoses accounted for 987,604 admissions in NSW over the study period, of
      which 3.7% were for Indigenous people. The age-standardised PPH admission rate
      was 76.5 and 27.3 per 1,000 for Indigenous and non-Indigenous people
      respectively. PPH admission rates in Indigenous people were 2.16 times higher
      than in non-Indigenous people of the same age group and sex who lived in the same
      SLA. The largest disparities in PPH admission rates were seen for diabetes
      complications, chronic obstructive pulmonary disease and rheumatic heart disease.
      Both rates of PPH admission in Indigenous people, and the disparity in rates
      between Indigenous than non-Indigenous people, varied significantly by SLA, with
      greater disparities seen in regional and remote areas than in major cities.
      CONCLUSIONS: Higher rates of PPH admission among Indigenous people are not simply
      a function of their greater likelihood of living in rural and remote areas. The
      very considerable geographic variation in the disparity in rates of PPH admission
      between Indigenous and non-Indigenous people indicates that there is potential to
      reduce unwarranted variation by characterising outlying areas which contribute
      the most to this disparity.

PMID- 24859266
TI  - Characterization of a quantitative method to measure free proprotein convertase
      subtilisin/kexin type 9 in human serum.
AB  - Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease that
      plays an important role in the regulation of serum low-density lipoprotein (LDL)
      cholesterol by downregulation of LDL receptor, and as such is considered a novel
      target in cholesterol lowering therapy. In support of the drug development
      program for Evolocumab, a fully human IgG2 antibody that targets PCSK9, a
      quantitative ELISA to measure free PCSK9 in human serum was developed. PCSK9
      serves as a biomarker of pharmacological response during treatment, and measuring
      levels of the free ligand post-dosing was of interest as an aid to establishing
      the pharmacokinetic and pharmacodynamic properties of the therapeutic. Given the
      complexities associated with the measurement of free ligand in the presence of
      high concentrations of circulating drug, it was important to challenge the method
      with experiments designed to assess ex vivo conditions that have the potential to
      affect the binding equilibrium of drug and ligand within test samples during
      routine sampling handling and assay conditions. Herein, we report results of
      experiments that were conducted to characterize the assay in alignment with
      regulatory guidance and industry standards, and to establish evidence that the
      method is measuring the free ligand in circulation at the time serum was
      collected. A robust supporting data package was generated that demonstrates the
      method specifically and reproducibly measures the free ligand, and is suitable
      for its intended use.

PMID- 24859267
TI  - Overexpression and biochemical characterization of a thermostable phytase from
      Bacillus subtilis US417 in Pichia pastoris.
AB  - The overexpression of the native gene encoding the thermostable Bacillus subtilis
      US417 phytase using Pichia pastoris system is described. The phytase gene, in
      which the sequence encoding the signal peptide was replaced by that of the alpha
      factor of Saccharomyces cerevisiae, was placed under the control of the methanol
      inducible promoter of the alcohol oxidase 1 gene and expressed in Pichia
      pastoris. Small-scale expression experiments and activity assays were used to
      screen positive colonies. A recombinant strain was selected and produces 43 and
      227 U/mL of phytase activity in shake flasks and in high-cell-density
      fermentation, respectively. The purified phytase was glycosylated protein and
      varied in size (50-65 kDa). It has a molecular mass of 43 kDa when it was
      deglycosylated. The purified r-PHY maintains 100% of its activity after 10 min
      incubation at 75  degrees C and pH 7.5. This thermostable phytase, which is also
      active over broad pH ranges, may be useful as feed additives, since it can resist
      the temperature used in the feed-pelleting process.

PMID- 24859268
TI  - Fine mapping of Co-x, an anthracnose resistance gene to a highly virulent strain
      of Colletotrichum lindemuthianum in common bean.
AB  - KEY MESSAGE: The Co - x anthracnose R gene of common bean was fine-mapped into a
      58 kb region at one end of chromosome 1, where no canonical NB-LRR-encoding genes
      are present in G19833 genome sequence. Anthracnose, caused by the phytopathogenic
      fungus Colletotrichum lindemuthianum, is one of the most damaging diseases of
      common bean, Phaseolus vulgaris. Various resistance (R) genes, named Co-,
      conferring race-specific resistance to different strains of C. lindemuthianum
      have been identified. The Andean cultivar JaloEEP558 was reported to carry Co-x
      on chromosome 1, conferring resistance to the highly virulent strain 100. To fine
      map Co-x, 181 recombinant inbred lines derived from the cross between JaloEEP558
      and BAT93 were genotyped with polymerase chain reaction (PCR)-based markers
      developed using the genome sequence of the Andean genotype G19833. Analysis of
      RILs carrying key recombination events positioned Co-x at one end of chromosome 1
      to a 58 kb region of the G19833 genome sequence. Annotation of this target region
      revealed eight genes: three phosphoinositide-specific phospholipases C (PI-PLC),
      one zinc finger protein and four kinases, suggesting that Co-x is not a classical
      nucleotide-binding leucine-rich encoding gene. In addition, we identified and
      characterized the seven members of common bean PI-PLC gene family distributed
      into two clusters located at the ends of chromosomes 1 and 8. Co-x is not a
      member of Co-1 allelic series since these two genes are separated by at least 190
      kb. Comparative analysis between soybean and common bean revealed that the Co-x
      syntenic region, located at one end of Glycine max chromosome 18, carries Rhg1, a
      major QTL contributing to soybean cyst nematode resistance. The PCR-based markers
      generated in this study should be useful in marker-assisted selection for
      pyramiding Co-x with other R genes.

PMID- 24859269
TI  - Embryo-fetal exposure and developmental outcome of thalidomide following oral and
      intravaginal administration to pregnant rabbits.
AB  - Studies in pregnant rabbits were conducted to evaluate if there are any
      differences in the uptake of thalidomide into the intrauterine compartment and
      developmental toxicity risk following oral and intravaginal administration.
      Thalidomide concentrations in maternal plasma, yolk sac cavity (YSC) fluid and
      embryo following intravaginal administration were 2- to 7-fold lower than their
      respective levels after oral administration. Ratios of thalidomide concentration
      in YSC fluid to maternal plasma were similar between these two routes, indicating
      no difference in uptake into the intrauterine compartment. A rabbit embryo-fetal
      development study using oral and intravaginal thalidomide administration at
      2mg/kg/day (a dose >10,000-fold higher than the expected amount of thalidomide in
      human semen) did not result in any developmental abnormalities. These data
      demonstrated no preferential transfer mechanism of thalidomide from vagina to
      conceptus, and no additional embryo-fetal developmental toxicity risks with
      thalidomide exposure via the vaginal route. 

PMID- 24859270
TI  - Cilia and ciliopathies: classic examples linking phenotype and genotype-an
      overview.
AB  - The importance of the role of cilia in pre and post natal development has been
      appreciated since the previous century. However, a better understanding of the
      physiological and, conversely, dysfunctional role that cilia have in
      developmental disease is still emerging. Dysfunctioning cilia can lead to
      diseases with a remarkable spectrum of phenotypes ranging from embryofetal
      lethality, through "classic" organ malformation to severe loss of function that
      leads to diseases during infancy or more subtle loss of function that may not
      become apparent until adulthood. Collectively, these diseased are termed
      ciliopathies. A shift in the focus of research by using tools and models that
      highlight the similarity between the genetics of mice, zebrafish and human cells,
      is starting to form an interesting mechanistic picture of how cilia have a role
      in the developmental pathologies and human diseases. Some of the underlying
      cellular principles, implicated genes and, where possible, mechanisms will be
      briefly described in this manuscript and there are several more detailed reviews
      available [Quinlan et al, 2008; Veland et al, 2009 and Norris and Grimes, 2013]. 

PMID- 24859271
TI  - Investigation of maternal and fetal exposure to an IgG2 monoclonal antibody
      following biweekly intravaginal administration to cynomolgus monkeys throughout
      pregnancy.
AB  - To assess the potential for male-mediated drug transfer to their female partner
      and/or developing conceptus, vaginal uptake of a monoclonal antibody (mAb)
      biotherapeutic was assessed in cynomolgus monkeys. A human IgG2 mAb (IgG2X; bound
      human and cynomolgus monkey neonatal Fc-receptor, FcRn, with similar high
      affinity) was administered intravaginally (IvG; 100mg/dose) to 5 pregnant
      cynomolgus monkeys biweekly from gestation day (gd) 21 to gd133. In all maternal
      samples collected before gd119, IgG2X plasma concentrations were below the limit
      of quantification (BLQ; <25ng/mL). After dosing on gd119 and 133, maternal IgG2X
      plasma concentrations remained BLQ in 3/5 monkeys and were very low in 2/5 (up to
      116ng/mL; ~0.01% of the IvG dose). IgG2X was BLQ in all fetal plasma samples.
      These data indicate that male-mediated mAb drug transfer via seminal fluid does
      not present a health risk to the female partner and is not bioavailable to the
      developing conceptus. 

PMID- 24859272
TI  - Genetic variations of IL-12B, IL-12Rbeta1, IL-12Rbeta2 in Behcet's disease and
      VKH syndrome.
AB  - PURPOSE: To investigate the associations of single nucleotide polymorphisms
      (SNPs) of three genes (IL-12B, IL-12Rbeta1 and IL-12Rbeta2) in Behcet's disease
      (BD) and Vogt-Koyanagi-Harada (VKH) syndrome in a Chinese Han population.
      METHODS: A total of 806 BD cases, 820 VKH patients, and 1600 healthy controls
      were involved in this study. The first investigation included 400 BD patients,
      400 VKH cases, and 600 healthy individuals. A second confirmatory study included
      a separate set of 406 BD patients, 420 VKH cases and another 1000 normal
      controls. Genotyping was carried out by PCR-restriction fragment length
      polymorphism assay and results were validated by using direct sequencing. The
      chi2 test was performed to compare the allele and genotype frequencies between
      cases and healthy controls. RESULTS: This study comprised two phases. In the
      first phase study, a significantly increased frequency of the rs3212227/IL-12B
      genotype CC and C allele was found in BD patients as compared to controls
      (Bonferroni corrected p value (pc) = 0.009, OR 1.8; pc = 0.024, OR 1.3,
      respectively). Moreover, the frequency of the C allele of rs3212227/IL-12B was
      also significantly increased in VKH patients (pc = 0.012, OR 1.3, 95% CI 1.1 to
      1.6). No associations were found for the other seven tested SNPs either in BD or
      VKH disease. The second study as well as the combined data confirmed the
      significant association of rs3212227/IL-12B with BD (CC genotype: combined pc =
      6.3*10(-7), OR = 1.8; C allele: combined pc = 2.0*10(-5), OR = 1.3, respectively)
      and the C allele frequency of rs3212227/IL-12B as the risk factor to VKH patients
      (combined pc = 2.5*10(-5), OR 1.3, 95% CI 1.2 to 1.5). CONCLUSIONS: Our study
      revealed that the IL-12B gene is involved both in the susceptibility to BD as
      well as VKH syndrome.

PMID- 24859273
TI  - Use of surface-enhanced Raman scattering to quantify EGFR markers uninhibited by
      cetuximab antibodies.
AB  - Epidermal growth factor receptor (EGFR) has been recognized as an important
      prognostic marker expressed in cancer cells because its activation is associated
      with key features of cancer including tumor growth, survival, angiogenesis, and
      metastasis. Cetuximab is the first monoclonal antibody drug that targets EGFR
      overexpressed in cancer cells. It easily binds to EGFR, thereby down-regulating
      the receptor, blocking EGFR-mediated tyrosine kinase activity, and inhibiting
      cellular proliferation. Thus, EGFR-cetuximab binding can be quantified to monitor
      receptor status and the prognosis of cancer therapy. In this work, we report
      using SERS imaging to assess the inhibitory effect of cetuximab on EGFR expressed
      on cancer cells. From SERS mapping images using silica-encapsulated gold
      nanotags, the localized spatial distribution of EGFR that was not inhibited by
      cetuximab could be determined. Furthermore, EGFR expression could be accurately
      quantified through the statistical analysis of surface-enhanced Raman scattering
      (SERS) spectral data. Our experimental data demonstrate the feasibility of SERS
      imaging to improve the prognostic efficacy of cetuximab treatment. 

PMID- 24859274
TI  - Decreased expression of CXCR4 chemokine receptor in bone marrow after
      chemotherapy in patients with non-Hodgkin lymphomas is a good prognostic factor.
AB  - BACKGROUND: CXCR4 chemokine receptor is constitutively expressed on normal and
      malignant B lymphocytes derived from patients with B-cell lymphoproliferative
      disorders and has a significant role in cell migration to lymph nodes and bone
      marrow. Non-Hodgkin's lymphomas (NHL) constitute a heterogeneous group of
      lymphoproliferative diseases, which can localize not only to lymph nodes, but
      also can migrate to peripheral blood and metastase to other organs, including
      bone marrow. AIM: The purpose of this study was to determine CXCR4 gene
      expression in peripheral blood and bone marrow of NHL patients before and after
      treatment. METHODS: Samples of lymphoma lymph nodes, peripheral blood and bone
      marrow aspirates of patients with B-cell NHL were taken at diagnosis and after
      chemotherapy. Gene expression was determined by the reverse transcription (RT)
      polymerase chain reaction method. Expression was estimated from 0 AU (no
      amplificate signal) to 3 AU (maximal amplificate signal). RESULTS: No significant
      difference in the level of CXCR4 expression was found in reactive lymph nodes
      compared to lymphoma samples We observed high level of CXCR4 expression in most
      patients before treatment: in bone marrow: 3 AU-10 pts, 2 AU-8 pts, 1 AU-2 pts.
      In peripheral blood: 3 AU-14 pts, 2 AU-4 pts, 1 AU-1 pts, 0 AU-1 pts. After
      chemotherapy, significant decrease in CXCR4 expression was observed. Bone marrow:
      3 AU-5 pts, 2 AU-7 pts, 1 AU-5 pts, 0 AU-3 pts (p = 0.03). Peripheral blood: 3 AU
      2 pts, 2 AU-6 pts, 1 AU-10 pts, 0 AU-2 pts (p = 0.0002). There was a good
      response to treatment in patients with significant decrease of CXCR4 expression
      in the bone marrow after treatment with 10-fold lower risk of death (p = 0.03).
      CONCLUSIONS: Decrease in CXCR4 expression in the bone marrow of NHL patients
      after chemotherapy may be a good prognostic factor.

PMID- 24859275
TI  - Lack of identification in semiparametric instrumental variable models with binary
      outcomes.
AB  - A parameter in a statistical model is identified if its value can be uniquely
      determined from the distribution of the observable data. We consider the context
      of an instrumental variable analysis with a binary outcome for estimating a
      causal risk ratio. The semiparametric generalized method of moments and
      structural mean model frameworks use estimating equations for parameter
      estimation. In this paper, we demonstrate that lack of identification can occur
      in either of these frameworks, especially if the instrument is weak. In
      particular, the estimating equations may have no solution or multiple solutions.
      We investigate the relationship between the strength of the instrument and the
      proportion of simulated data sets for which there is a unique solution of the
      estimating equations. We see that this proportion does not appear to depend
      greatly on the sample size, particularly for weak instruments (rho(2) <= 0.01).
      Poor identification was observed in a considerable proportion of simulated data
      sets for instruments explaining up to 10% of the variance in the exposure with
      sample sizes up to 1 million. In an applied example considering the causal effect
      of body mass index (weight (kg)/height (m)(2)) on the probability of early
      menarche, estimates and standard errors from an automated optimization routine
      were misleading. 

PMID- 24859276
TI  - Incidence of dementia among participants and nonparticipants in a longitudinal
      study of cognitive aging.
AB  - Although rates of incident dementia have been reported from several populations,
      the impact of nonparticipation on dementia incidence in studies of cognitive
      aging is unknown. In 2004, investigators with the Mayo Clinic Study of Aging
      selected persons aged 70-89 years from an enumeration of all Olmsted County,
      Minnesota, residents (age- and sex-stratified random sample). Of 4,398 potential
      participants, 2,050 agreed to undergo an in-person health assessment. Those
      participants were reevaluated in person using standard diagnostic procedures
      approximately every 15 months over a median follow-up period of 5.7 years
      (through September 15, 2013). There were 1,679 persons who refused any
      participation. A trained nurse abstractor reviewed the medical records of
      nonparticipants using the Rochester Epidemiology Project's medical record linkage
      system a median of 3.9 years after refusal. Nonparticipants had a higher
      prevalence of dementia than participants evaluated in person (6.5% vs. 3.3%; P <
      0.0001). The standardized incidence of dementia was not significantly higher
      among the nonparticipants (23.2 per 1,000 person-years) than in those evaluated
      in person (19.6 per 1,000 person-years; hazard ratio = 1.17, 95% confidence
      interval: 0.95, 1.43 (P = 0.13); adjusted for education and sex, with age as the
      time scale). The small, nonsignificant impact of nonparticipation on rates of
      incident dementia is reassuring for future studies based on incident dementia
      cases. 

PMID- 24859277
TI  - Antigenic variation in African trypanosomes.
AB  - Studies on Variant Surface Glycoproteins (VSGs) and antigenic variation in the
      African trypanosome, Trypanosoma brucei, have yielded a remarkable range of novel
      and important insights. The features first identified in T. brucei extend from
      unique to conserved-among-trypanosomatids to conserved-among-eukaryotes.
      Consequently, much of what we now know about trypanosomatid biology and much of
      the technology available has its origin in studies related to VSGs. T. brucei is
      now probably the most advanced early branched eukaryote in terms of experimental
      tractability and can be approached as a pathogen, as a model for studies on
      fundamental processes, as a model for studies on eukaryotic evolution or often
      all of the above. In terms of antigenic variation itself, substantial progress
      has been made in understanding the expression and switching of the VSG coat,
      while outstanding questions continue to stimulate innovative new approaches.
      There are large numbers of VSG genes in the genome but only one is expressed at a
      time, always immediately adjacent to a telomere. DNA repair processes allow a new
      VSG to be copied into the single transcribed locus. A coordinated transcriptional
      switch can also allow a new VSG gene to be activated without any detectable
      change in the DNA sequence, thereby maintaining singular expression, also known
      as allelic exclusion. I review the story behind VSGs; the genes, their expression
      and switching, their central role in T. brucei virulence, the discoveries that
      emerged along the way and the persistent questions relating to allelic exclusion
      in particular. 

PMID- 24859280
TI  - Rheological properties vs. local dynamics in model disordered materials at low
      temperature.
AB  - We study the rheological response at low temperature of a sheared model
      disordered material as a function of the bond rigidity. We find that the flow
      curves follow a Herschel-Bulkley law, whatever is the bond rigidity, with an
      exponent close to 0.5. Interestingly, the apparent viscosity can be related to a
      single relevant time scale t rel, suggesting a strong connection between the
      local dynamics and the global mechanical behaviour. We propose a model based on
      the competition between the nucleation and the avalanche-like propagation of
      spatial strain heterogeneities. This model can explain the Herschel-Bulkley
      exponent on the basis of the size dependence of the heterogeneities on the shear
      rate. 

PMID- 24859279
TI  - A microrheological study of hydrogel kinetics and micro-heterogeneity.
AB  - The real-time dynamic heterogeneity of the gelation process of the amino acid
      derivative Fmoc-tyrosine (Fmoc-Y) is studied using particle tracking
      microrheology. To trigger gelation, glucono-delta-lactone (GdL) is added, which
      gradually lowers the p H over several hours. The onset of self-assembly in the
      system is signified by a sharp drop in the mean-squared displacement of embedded
      particles, a phenomenon that is found to correlate with the p H of the system
      reaching the pK(a) of Fmoc-Y. The gel point is identified and found to be
      dependent on the GdL concentration. Analysis of embedded probe particle dynamics
      allows the heterogeneity of the sample to be quantified, using three metrics: the
      heterogeneity ratio (HR), the non-Gaussian parameter of the van Hove correlation
      function (N and the bin distribution of the mean-squared displacement (MSD) of
      single particles (f(z)). Results from the three techniques are found to be
      approximately comparable, with increases in heterogeneity observed in all samples
      for incubation times t(w) = 0-3 hours. The final heterogeneity in all samples is
      found to be remarkably low compared to other systems previously reported in the
      literature.

PMID- 24859281
TI  - Shape and energy of a membrane bud induced by protein coats or viral protein
      assembly.
AB  - Intracellular transport vesicles and enveloped virus production is mediated by
      the polymerization of proteins that form bi-dimensional curved and rigid
      structures, or "coats", on a membrane. Using the classical framework of fluid
      membrane elasticity, we compute numerically the shape and the mechanical energy
      of the membrane deformation induced by a coat at different stage of growth. We
      furthermore derive analytical approximate expressions for the membrane shape and
      energy. They are found to be very accurate when compared to numerical
      calculations. These analytical expressions should be useful when building a
      relevant model of coat polymerization kinetics. We also discuss some consequences
      of the membrane energy features on the coat assembly process, showing that at
      high tension a kinetically arrested state of incomplete assembly could exist. 

PMID- 24859278
TI  - Prolactin induces apoptosis of lactotropes in female rodents.
AB  - Anterior pituitary cell turnover occurring during female sexual cycle is a poorly
      understood process that involves complex regulation of cell proliferation and
      apoptosis by multiple hormones. In rats, the prolactin (PRL) surge that occurs at
      proestrus coincides with the highest apoptotic rate. Since anterior pituitary
      cells express the prolactin receptor (PRLR), we aimed to address the actual role
      of PRL in the regulation of pituitary cell turnover in cycling females. We showed
      that acute hyperprolactinemia induced in ovariectomized rats using PRL injection
      or dopamine antagonist treatment rapidly increased apoptosis and decreased
      proliferation specifically of PRL producing cells (lactotropes), suggesting a
      direct regulation of these cell responses by PRL. To demonstrate that apoptosis
      naturally occurring at proestrus was regulated by transient elevation of
      endogenous PRL levels, we used PRLR-deficient female mice (PRLRKO) in which PRL
      signaling is totally abolished. According to our hypothesis, no increase in
      lactotrope apoptotic rate was observed at proestrus, which likely contributes to
      pituitary tumorigenesis observed in these animals. To decipher the molecular
      mechanisms underlying PRL effects, we explored the isoform-specific pattern of
      PRLR expression in cycling wild type females. This analysis revealed dramatic
      changes of long versus short PRLR ratio during the estrous cycle, which is
      particularly relevant since these isoforms exhibit distinct signaling properties.
      This pattern was markedly altered in a model of chronic PRLR signaling blockade
      involving transgenic mice expressing a pure PRLR antagonist (TGDelta1-9-G129R
      hPRL), providing evidence that PRL regulates the expression of its own receptor
      in an isoform-specific manner. Taken together, these results demonstrate that i)
      the PRL surge occurring during proestrus is a major proapoptotic signal for
      lactotropes, and ii) partial or total deficiencies in PRLR signaling in the
      anterior pituitary may result in pituitary hyperplasia and eventual prolactinoma
      development, as observed in TGDelta1-9-G129R-hPRL and PRLRKO mice, respectively. 

PMID- 24859282
TI  - Luteolin and quercetin affect the cholesterol absorption mediated by epithelial
      cholesterol transporter niemann-pick c1-like 1 in caco-2 cells and rats.
AB  - Niemann-Pick C1-Like 1 (NPC1L1) mediates cholesterol absorption, and ezetimibe is
      a potent NPC1L1 inhibitor applicable for medication of hypercholesterolemia.
      Epidemiological studies demonstrated that consumption of polyphenols correlates
      with a decreased risk for atherosclerosis due to their antioxidant effect. This
      activity can hardly be attributable to the antioxidant activity only, and we
      hypothesized that polyphenols inhibit intestinal transport of cholesterol. We
      elucidated the kinetic parameters of intestinal cholesterol absorption, screened
      several polyphenols for their ability to specifically inhibit intestinal
      cholesterol absorption, and determined the inhibitory effects of selected
      flavonoids in vitro and in vivo. The concentration-dependent uptake of
      cholesterol by Caco-2 cells obeyed a monophasic saturation process. This
      indicates the involvement of an active-passive transport, i.e., NPC1L1.
      Parameters of cholesterol uptake by Caco-2 cells were as follows: Jmax, Kt, and
      Kd were 6.89+/-2.96 19.03+/-11.58 uM, and 0.11+/-0.02 pmol/min/mg protein,
      respectively. Luteolin and quercetin inhibited cholesterol absorption by Caco-2
      cells and human embryonic kidney 293T cells expressing NPC1L1. When preincubated
      Caco-2 cells with luteolin and quercetin before the assay, cholesterol uptake
      significantly decreased. The inhibitory effects of these flavonoids were
      maintained for up to 120 min. The level of inhibition and irreversible effects
      were similar to that of ezetimibe. Serum cholesterol levels significantly
      decreased more in rats fed both cholesterol and luteolin (or quercetin), than in
      those observed in the cholesterol feeding group. As quercetin induced a
      significant decrease in the levels of NPC1L1 mRNA in Caco-2 cells, the in vivo
      inhibitory effect may be due to the expression of NPC1L1. These results suggest
      that luteolin and quercetin reduce high blood cholesterol levels by specifically
      inhibiting intestinal cholesterol absorption mediated by NPC1L1. 

PMID- 24859284
TI  - Dynamic expression patterns of ATF3 and p53 in the hippocampus of a
      pentylenetetrazole-induced kindling model.
AB  - Epilepsy is a common and often deleterious neurological condition. Emerging
      evidence has demonstrated the roles of innate immunity and the associated
      inflammatory processes in epilepsy. In a previous study, we found that Toll-like
      receptors (TLRs) are upregulated and promote mossy fiber sprouting (MFS) in an
      epileptic model. As downstream effectors of TLRs, the activating transcription
      factor 3 (ATF3) and p53 proteins were shown to be involved in neurite outgrowth.
      In the present study, we hypothesized that ATF3 and p53 participate in the
      process of epilepsy and can affect MFS. To investigate this hypothesis, we
      examined the expression of ATF3 and p53 in hippocampal tissues of rats kindled by
      pentylenetetrazole (PTZ) using immunofluorescence, immunohistochemistry and
      western blotting. MFS was evaluated by Timm staining in the hippocampus. Results
      from these experiments revealed that expression of ATF3 and p53 is significantly
      higher (p<0.05) in the CA3 area of the hippocampus in the PTZ-treated group
      compared to the control group. ATF3 expression gradually increased from 3 days to
      4 weeks, peaked at 4 weeks and decreased slightly at 6 weeks in the PTZ group,
      while the expression of p53 was maintained at similar levels at different time
      points following PTZ treatment. No obvious difference in the expression of these
      proteins was observed between the PTZ and the control group in the dentate gyrus
      (DG) area (p>0.05). The degree of MFS in the PTZ group peaked at 4 weeks and was
      maintained at a high level until 6 weeks post-PTZ treatment. In conclusion, ATF3
      and p53 may be involved in the occurrence of seizure and play critical roles in
      MFS in the PTZ kindling model. 

PMID- 24859285
TI  - Fabrication, characterization, and biocompatibility of ethyl cellulose/carbonated
      hydroxyapatite composite coatings on Ti6Al4V.
AB  - In order to improve the biocompatibility of metallic implants, bioactive
      components are often used as coatings so that a real bond with the surrounding
      bone tissue can be formed. We prepared ethyl cellulose/carbonated hydroxyapatite
      composite coatings (ECHCs) on Ti6Al4V substrates with carbonated hydroxyapatite
      coatings (CHACs) without ethyl cellulose as controls. The inorganic constituent
      on the CHACs and ECHCs is calcium-deficient carbonated hydroxyapatite with a
      flaky texture and a low degree of crystallinity. The flaky carbonated
      hydroxyapatite plates aggregate to form macropores with an aperture size of
      around 0.5-2.0 MUm. The presence of ethyl cellulose provides superior morphology,
      contact angle, and biocompatibility characteristics. In comparison to CHACs,
      ECHCs exhibit a smoother, crack-free surface because the cracks are filled by
      ethyl cellulose. Moreover, the contact angle of ECHCs is 37.3 degrees , greater
      than that of CHACs (13.0 degrees ). Surface biocompatibility was investigated by
      using human bone mesenchymal stem cells (hBMSCs). The attachment, spreadability,
      viability and proliferation of hBMSCs on ECHCs are superior to those on CHACs.
      Thus, the crack-free ECHCs have excellent biocompatibility and are appropriate
      for use as biological implants. 

PMID- 24859286
TI  - An open platform for personal health record apps with platform-level privacy
      protection.
AB  - One of the main barriers to the adoption of Personal Health Records (PHR) systems
      is their closed nature. It has been argued in the literature that this barrier
      can be overcome by introducing an open market of substitutable PHR apps. The
      requirements introduced by such an open market on the underlying platform have
      also been derived. In this paper, we argue that MyPHRMachines, a cloud-based PHR
      platform recently developed by the authors, satisfies these requirements better
      than its alternatives. The MyPHRMachines platform leverages Virtual Machines as
      flexible and secure execution sandboxes for health apps. MyPHRMachines does not
      prevent pushing hospital- or patient-generated data to one of its instances, nor
      does it prevent patients from sharing data with their trusted caregivers.
      External software developers have minimal barriers to contribute innovative apps
      to the platform, since apps are only required to avoid pushing patient data
      outside a MyPHRMachines cloud. We demonstrate the potential of MyPHRMachines by
      presenting two externally contributed apps. Both apps provide functionality going
      beyond the state-of-the-art in their application domain, while they did not
      require any specific MyPHRMachines platform extension. 

PMID- 24859287
TI  - Airway changes in pregnant women before and after delivery.
AB  - AIM: High incidence of difficult or failed intubation in obstetric patients is
      still a major problem to challenge anaesthesiologists. Although the probability
      of difficult intubation is impossible to predict preoperatively, some simple,
      practical bedside tests may help. This study used five simple tests in an attempt
      to better evaluate airway changes in pregnant women before and after delivery.
      MATERIALS AND METHODS: Pregnant women from the ASA I-II group who were planning
      to undergo a normal vaginal delivery were evaluated as to the possibility of
      experiencing difficult intubation. Mallampati scores, thyromental distance,
      sternomental distance, mouth opening, and the degree of neck extension were
      recorded just before delivery and 24 h after delivery. RESULTS: Significant
      differences were seen in the pre- and post-delivery measurements (p < 0.05).
      Before delivery, Mallampati scores I, II, III, IV were 35, 24, 2, 0,
      respectively, and 24 h after delivery became 46, 15, 0, 0, respectively.
      CONCLUSIONS: Within 24 h after delivery, Mallampati scores changed in one-third
      (n 21, 36.6%) of the patients. Significant differences between the two
      measurements of thyromental and sternomental distances, mouth opening, and the
      degree of neck extension confirm difficult airway management in pregnant women.

PMID- 24859288
TI  - The double-edged sword of vitamin D in Ireland: the need for public health
      awareness about too much as well as too little.
AB  - INTRODUCTION: The Institute of Medicine (IOM) 2011 on dietary references intakes
      for calcium and vitamin D specified that a 25-hydroxyvitamin D (25OHD) level
      below 30 nmol/L indicated risk of deficiency and that a level above 125 nmol/L
      indicated risk of harm. METHODS: We noted a high prevalence of hypovitaminosis D
      (23.9 %) and a substantive prevalence of hypervitaminosis D (4.8 %) in a
      retrospective audit of clinical samples (n = 10,181) obtained over 10 months in
      2013. CONCLUSION: Hypovitaminosis D should be corrected by low dose
      supplementation (5 ug or 200 IU daily) with some at-risk groups needing higher
      doses (10 ug or 400 IU daily) based on 25OHD levels. Whereas, those taking high
      dose vitamin D supplements based on mistaken beliefs about recently authorised
      claims of benefit for muscle function and misleading unauthorised claims need to
      be alerted to the potential harms of excessive supplementation.

PMID- 24859289
TI  - Antifungal Enantiomeric Styrylpyrones from Sanrafaelia ruffonammari and
      Ophrypetalum odoratum.
AB  - Phytochemical investigation of Sanrafaelia ruffonammari Verd and Ophrypetalum
      odoratum Diels that belongs to the rare genera confined to East African coastal
      forests led to the isolation of enantiomeric styrylpyrone dimer, (+/-)-5-methoxy
      7-phenyl-[4-methoxy-2-pyronyl]-1-(E)-styryl-2-oxabicyclo-[4.2.0]-octa-4-en-3-one
      (1) alongside (+)-6-styryl-7,8-epoxy-4-methoxypyran-2-one (2) and the
      enantiomeric (+)- (3) and (-)-6-styryl-7,8-dihydroxy-4-methoxypyran-2-ones (4).
      Their structures were established by means of spectroscopic methods. In this
      paper we reveal for the first time the occurrence of styrylpyrones in East
      African biodiversity. (+)-6-Styryl-7,8-epoxy-4-methoxypyran-2-one (2) and the
      dihydroxystyrylpyrone enantiomer (3) showed in vitro antifungal activity against
      Candida albicans at a concentration of 24.4 and 26.2 uM with zones of inhibition
      of 17 and 9 mm, respectively. Compound 2 exhibited strong activity in the brine
      shrimp test with LC50 = 1.7 ug/mL. Their high cytotoxic and antifungal activities
      render them candidates for further scientific attention for drug development
      programs against cancer and microbial infections. 

PMID- 24859290
TI  - Red blood cell distribution width is associated with early failure of
      arteriovenous fistula for haemodialysis access.
AB  - This study aimed to investigate the predictive value of red blood cell
      distribution width (RDW) for early failure of arteriovenous fistula (AVF) for
      haemodialysis access. The hospital records of those patients who underwent
      primary AVF creation procedures for haemodialysis between December 2010 and
      September 2013 were included for retrospective analysis. Of 313 patients, 195
      (62%) were male and 118 (38%) were female. Mean age was 60 (range 17-90) years.
      Of the 313 AVF procedures performed, 229 (73%) were created at forearm (radial
      artery-cephalic vein), and 84 (27%) were created upperarm (antecubital,
      brachiocephalic, or brachiobasilic procedures). Early AVF failure was found in 61
      (19%) patients. According to chi-square test, the incidence of early AVF failure
      was higher in patients with heart failure and peripheral artery disease (P <
      0.001). According to Mann-Whitney U test, the RDW (P = 0.001) and C-reactive
      protein (P = 0.024) values were higher in patients with early AVF. Our data
      showed that preoperative RDW is a reliable parameter that can be useful in
      predicting the early failure of AVF. 

PMID- 24859291
TI  - In vitro and ex vivo antimicrobial efficacy of nano-MgO in the elimination of
      endodontic pathogens.
AB  - OBJECTIVES: The use of metal oxide nanoparticles has attracted lots of attention,
      mostly because of their promising antimicrobial activity along with their
      biocompatibility with mammalian cells. This study aims to investigate the in
      vitro and ex vivo antimicrobial efficiency of nano-magnesium oxide (MgO) aqueous
      solution against endodontic pathogens. MATERIALS AND METHODS: The cytotoxicity of
      different concentrations of nano-MgO was assessed using lactate dehydrogenase
      cytotoxicity assay (LDH assay). A comparison of the antimicrobial efficiency of
      several concentrations of nano-MgO solution, sodium hypochlorite (NaOCl), and
      chlorhexidine (CHX) gluconate against Staphylococcus aureus, Enterococcus
      faecalis, and Candida albicans was made using the direct contact method. An ex
      vivo model of decoronated and experimentally infected human teeth was employed to
      compare the efficiency of nano-MgO (5 mg/L) solution with NaOCl (5.25 %) in the
      elimination of E. faecalis. RESULTS: There was no statistically significant
      difference between nano-MgO solutions (10 and 5 mg/L), 5.25 % NaOCl, and 2 % CHX
      gluconate in terms of the required time to inhibit the growth of the tested
      pathogens (p > 0.05). The LDH assay showed no cytotoxicity of different
      concentrations of nano-MgO used in this study (p < 0.001). In the ex vivo model
      of infected human teeth, 6 h post-irrigation, there was no statistically
      significant difference between colony-forming units (CFU) per milliliter of nano
      MgO (5 mg/L) and NaOCl (5.25 %)-treated teeth (5-6 log scale reduction). However,
      the nano-MgO group showed a significant decrease in colony-forming units per
      milliliter (7 log scale), 24 h post-irrigation (p < 0.05). At other tested time
      points-24, 48, 72, and 168 h-the levels of CFU per milliliter were significantly
      less in the nano-MgO group (2-3 log scale difference) compared to the NaOCl
      group, indicating long-term antibacterial activity of nano-MgO (p < 0.05). At 72
      and 168 h post-irrigation, no detectable bacterial growth was observed in the
      nano-MgO group. The detection limit was 10 CFU/mL. CONCLUSIONS: Nano-MgO aqueous
      solutions represent promising antimicrobial activities, both in vitro and ex vivo
      with minimal toxicity. CLINICAL RELEVANCE: Compared to NaOCl (5.25 %), nano-MgO
      (5 mg/L) exhibits statistically significant long-term efficiency in the
      elimination of E. faecalis in the root canal system. After further
      investigations, nano-MgO could be considered as a new root canal irrigant.

PMID- 24859292
TI  - Serum brain-derived neurotrophic factor and cognitive functioning in underweight,
      weight-recovered and partially weight-recovered females with anorexia nervosa.
AB  - Several studies support the assumption that the brain-derived neurotrophic factor
      (BDNF) plays an important role in the pathophysiology of eating disorders. In the
      present cross-sectional and longitudinal study, we investigated BDNF levels in
      patients with anorexia nervosa (AN) at different stages of their illness and the
      association with cognitive functioning. We measured serum BDNF in 72 acutely
      underweight female AN patients (acAN), 23 female AN patients who successfully
      recovered from their illness (recAN), and 52 healthy control women (HCW).
      Longitudinally, 30 acAN patients were reassessed after short-term weight gain.
      The association between BDNF levels and psychomotor speed was investigated using
      the Trail Making Test. BDNF serum concentrations were significantly higher in
      recAN participants if compared to acAN patients and increased with short-term
      weight gain. In acAN patients, but not HCW, BDNF levels were inversely associated
      with psychomotor speed. AcAN patients with higher BDNF levels also had lower life
      time body mass indexes. Taken together, our results indicate that serum BDNF
      levels in patients with AN vary with the stage of illness. Based on the
      pleiotropic functions of BDNF, changing levels of this neurotrophin may have
      different context-dependent effects, one of which may be the modulation of
      cognitive functioning in acutely underweight patients. 

PMID- 24859294
TI  - Banded structures in collagen vitrigels for corneal injury repair.
AB  - There is a growing interest in using collagen vitrigels for corneal injury
      repair. We recently reported the synthesis and thermal denaturation behavior of
      these gels. In this paper, the banded structure in these vitrified gels is
      studied by small-angle X-ray scattering (SAXS) one-dimensional (1-D) correlation
      function analysis and transmission electron microscopy (TEM). Results demonstrate
      that the collagen vitrigel possess banded structures similar to those of the
      starting type I collagen, with an average D-spacing of 64nm (by SAXS) or 57nm (by
      TEM). A combination of SAXS 1-D correlation function analyses and TEM show that
      overlap and gap distances ranged from 30 to 33nm and from 23 to 25nm,
      respectively. Changing the vitrification condition does not impact on the banded
      structure significantly. 

PMID- 24859293
TI  - Oak root response to ectomycorrhizal symbiosis establishment: RNA-Seq derived
      transcript identification and expression profiling.
AB  - Ectomycorrhizal symbiosis is essential for the life and health of trees in
      temperate and boreal forests where it plays a major role in nutrient cycling and
      in functioning of the forest ecosystem. Trees with ectomycorrhizal root tips are
      more tolerant to environmental stresses, such as drought, and biotic stresses
      such as root pathogens. Detailed information on these molecular processes is
      essential for the understanding of symbiotic tissue development in order to
      optimize the benefits of this natural phenomenon. Next generation sequencing
      tools allow the analysis of non model ectomycorrhizal plant-fungal interactions
      that can contribute to find the "symbiosis toolkits" and better define the role
      of each partner in the mutualistic interaction. By using 454 pyrosequencing we
      compared ectomycorrhizal cork oak roots with non-symbiotic roots. From the two
      cDNA libraries sequenced, over 2 million reads were obtained that generated
      19,552 cork oak root unique transcripts. A total of 2238 transcripts were found
      to be differentially expressed when ECM roots were compared with non-symbiotic
      roots. Identification of up- and down-regulated gens in ectomycorrhizal roots
      lead to a number of insights into the molecular mechanisms governing this
      important symbiosis. In cork oak roots, ectomycorrhizal colonization resulted in
      extensive cell wall remodelling, activation of the secretory pathway, alterations
      in flavonoid biosynthesis, and expression of genes involved in the recognition of
      fungal effectors. In addition, we identified genes with putative roles in
      symbiotic processes such as nutrient exchange with the fungal partner, lateral
      root formation or root hair decay. These findings provide a global overview of
      the transcriptome of an ectomycorrhizal host root, and constitute a foundation
      for future studies on the molecular events controlling this important symbiosis.

PMID- 24859295
TI  - Exposure to ingested airborne pollutant particulate matter increases mucosal
      exposure to bacteria and induces early onset of inflammation in neonatal IL-10
      deficient mice.
AB  - BACKGROUND: Epidemiological associations between early-life air pollution
      exposure and increased risk of inflammatory bowel diseases have been shown. Our
      aim was to determine if exposure to airborne particulate matter (PM(10)) during
      the neonatal period would alter colitis in the interleukin (IL)-10(-/-) mouse
      model. METHODS: IL-10(-/-) pregnant dams and pups were fed chow +/- PM(10) (9
      MUg/g) and pups were studied at 10, 14, and 20 weeks. Twenty-week-old mice were
      given 2% dextran sodium sulfate. Metagenomic analysis of stool was performed.
      Bacterial translocation was assessed by serum lipopolysaccharide and culturing
      bacteria from mesenteric lymph nodes and spleen. Cytokine expression was measured
      in gut homogenates using the MesoScale discovery platform. PM(10) was applied to
      CMT93 cells +/- J744 macrophages, and resistance and cytokine secretion were
      assessed. THP-1 macrophages were incubated with Escherichia coli HB101 +/- PM(10)
      for assessment of uptake and killing. RESULTS: PM(10) exposure increased colonic
      proinflammatory cytokines and bacterial translocation into mesenteric lymph
      nodes, whereas IL-17A levels were reduced in PM(10)-fed 10-week-old mice.
      Bifidobacterium was decreased in mice fed PM(10), whereas serum
      lipopolysaccharide was increased. PM(10) interfered with phagocytosis and killing
      in THP-1 cells. In coculture, PM(10) increased tumor necrosis factor alpha and
      fluorescein isothiocyanate-dextran flux. After dextran sodium sulfate treatment,
      PM10-fed mice responded with increased colonic tumor necrosis factor alpha and IL
      1beta and a larger percentage of PM(10)-fed mice had live bacteria in the
      mesenteric lymph nodes. CONCLUSIONS: Our data suggest that early exposure to
      pollution particulates can result in an earlier onset of intestinal disease in
      genetically susceptible hosts and can alter responses to gut injury in later
      life.

PMID- 24859296
TI  - Expression stability of common housekeeping genes is differently affected by
      bowel inflammation and cancer: implications for finding suitable normalizers for
      inflammatory bowel disease studies.
AB  - Instability of housekeeping genes (HKG), supposedly unregulated and hence used as
      normalizers, may dramatically change conclusions of quantitative PCR experiments.
      The effect of bowel inflammation on HKG remains unknown. Expression stability of
      15 HKG (ACTB, B2M, GAPDH, GUSB, HPRT1, IPO8, MRPL19, PGK1, PPIA, RPLP0, RPS23,
      SDHA, TBP, UBC, and YWHAZ) in 166 bowel specimens (91 normal, 35 cancerous, and
      40 inflamed) was ranked by coefficients of variation (CV%) or using dedicated
      software: geNorm and NormFinder. The RPS23, PPIA, and RPLP0 were top-ranked,
      whereas IPO8, UBC and TBP were the lowest-ranked HKG across
      inflamed/cancerous/normal colonic tissues. The pairs RPS23/RPLP0, PGK1/MRPL19, or
      PPIA/RPLP0 were optimal reference by CV%, NormFinder, and geNorm, respectively.
      Colon inflammation affected HKG more pronouncedly than cancer with ACTB
      significantly down- and B2M upregulated. In inflammatory bowel disease (IBD),
      different genes were top-ranked in a large and small bowel, whereas TBP, UBC, and
      IPO8 were lowest-ranked in both. For patients with IBD at large, RPS23/PPIA,
      PGK1/MRPL19, and PPIA/RPLP0 were found optimal by CV%, NormFinder, and geNorm,
      respectively. ACTB and B2M expression was related to CRC stage and positively
      correlated with clinical activity of IBD. Although GAPDH was upregulated neither
      in CRC nor IBD, it tended to positively correlate with tumor depth and Crohn's
      disease activity index. Normalizing against GAPDH affected experimental
      conclusions in a small but not large bowel. Bowel inflammation significantly
      affects several classic HKG. The pair PPIA/RPLP0 is a common optimal reference
      for studies encompassing tissues sampled from colorectal cancer and IBD patients.
      Using ACTB or B2M is not recommended.

PMID- 24859297
TI  - Natural history of Crohn's disease following total colectomy and end ileostomy.
AB  - BACKGROUND: Crohn's disease (CD) requires surgical management in up to two-thirds
      of patients. Few studies have addressed the issue of ileal recurrence after
      colectomy and permanent ileostomy. The aims of our study were to assess the rate
      and predictors of postoperative recurrence of CD in patients with permanent
      ileostomy. METHODS: In a retrospective study from a tertiary referral center, we
      analyzed the natural history of patients with CD who underwent total colectomy
      and permanent ileostomy. Our primary outcomes were (1) overall disease recurrence
      including luminal recurrence, perianal disease or peristomal lesions requiring
      therapy, and (2) luminal recurrence alone defined as endoscopic and clinical
      recurrence within the terminal ileum. We examined if patient characteristics
      predicted recurrence using multivariate Cox proportional hazard models. RESULTS:
      Our study included 73 patients with CD followed for a mean of 28 months (range, 0
      168 mo) after total colectomy and permanent ileostomy. Twenty patients had
      overall disease recurrence within 10 years after surgery, at rates of 15% and 50%
      at 1 and 5 years, respectively. Rate of luminal recurrence was 8% and 35% at 1
      and 5 years, respectively. Diagnosis at age less than 18 years (hazard ratio,
      2.94; 95% confidence interval, 1.14-7.62) and anti-tumor necrosis factor therapy
      before surgery (hazard ratio, 4.75; 95% confidence interval, 1.25-18.13) were the
      only independent predictive factors for overall disease recurrence. CONCLUSIONS:
      Up to one-third of patients with CD have overall recurrence of disease after
      treatment with total colectomy and permanent ileostomy. There is need to develop
      algorithms for surveillance and management of this select subgroup of patients.

PMID- 24859299
TI  - Dual role of MAPK pathway in the regulation of intestinal barrier function.

PMID- 24859300
TI  - The dual role of MAPK pathway in the regulation of intestinal barrier: the role
      of the commensal bacterium Faecalibacterium prausnitzii on this regulation.

PMID- 24859301
TI  - Beneficial effects of exclusive enteral nutrition in Crohn's disease are not
      mediated by Faecalibacterium prausnitzii.

PMID- 24859302
TI  - Role of Faecalibacterium prausnitzii in Crohn's Disease: friend, foe, or does not
      really matter?

PMID- 24859298
TI  - Potential for developing purinergic drugs for gastrointestinal diseases.
AB  - Treatments for inflammatory bowel disease (IBD), irritable bowel syndrome (IBS),
      functional dyspepsia, or motility disorders are not adequate, and purinergic
      drugs offer exciting new possibilities. Gastrointestinal symptoms that could be
      targeted for therapy include visceral pain, inflammatory pain, dysmotility,
      constipation, and diarrhea. The focus of this review is on the potential for
      developing purinergic drugs for clinical trials to treat gastrointestinal
      symptoms. Purinergic receptors are divided into adenosine P1 (A(1), A(2A), A(2B),
      A(3)), ionotropic ATP-gated P2X ion channel (P2X(1-7)), or metabotropic
      P2Y(1,2,4,6,11-14) receptors. There is good experimental evidence for targeting
      A(2A), A(2B), A(3), P2X(7), and P2X(3) receptors or increasing endogenous
      adenosine levels to treat IBD, inflammatory pain, IBS/visceral pain, inflammatory
      diarrhea, and motility disorders. Purine genes are also potential biomarkers of
      disease. Advances in medicinal chemistry have an accelerated pace toward clinical
      trials: Methotrexate and sulfasalazine, used to treat IBD, act by stimulating
      CD73-dependent adenosine production. ATP protects against NSAID-induced
      enteropathy and has pain-relieving properties in humans. A P2X(7)R antagonist
      AZD9056 is in clinical trials for Crohn's disease. A(3) adenosine receptor drugs
      target inflammatory diseases (e.g., CF101, CF102). Dipyridamole, a nucleoside
      uptake inhibitor, is in trials for endotoxemia. Drugs for pain in clinical trials
      include P2X(3)/P2X(2/3) (AF-219) and P2X(7) (GSK1482160) antagonists and A(1)
      (GW493838) or A(2A) (BVT.115959) agonists. Iberogast is a phytopharmacon
      targeting purine mechanisms with efficacy in IBS and functional dyspepsia.
      Purinergic drugs have excellent safety/efficacy profile for prospective clinical
      trials in IBD, IBS, functional dyspepsia, and inflammatory diarrhea. Genetic
      polymorphisms and caffeine consumption may affect susceptibility to treatment.
      Further studies in animals can clarify mechanisms and test new generation drugs.
      Finally, there is still a huge gap in our knowledge of human pathophysiology of
      purinergic signaling.

PMID- 24859303
TI  - Cigarette smoking and gastrointestinal diseases: the causal relationship and
      underlying molecular mechanisms (review).
AB  - Cigarette smoking is an important risk factor for gastrointestinal (GI)
      disorders, including peptic ulcers, inflammatory bowel diseases, such as Crohn's
      disease and cancer. In this review, the relationship between smoking and GI
      disorders and the underlying mechanisms are discussed. It has been demonstrated
      that cigarette smoking is positively associated with the pathogenesis of peptic
      ulcers and the delay of ulcer healing. Mechanistic studies have shown that
      cigarette smoke and its active ingredients can cause mucosal cell death, inhibit
      cell renewal, decrease blood flow in the GI mucosa and interfere with the mucosal
      immune system. Cigarette smoking is also an independent risk factor for various
      types of cancer of the GI tract. In this review, we also summarize the mechanisms
      through which cigarette smoking induces tumorigenesis and promotes the
      development of cancer in various sections of the GI tract. These mechanisms
      include the activation of nicotinic acetylcholine receptors, the formation of DNA
      adducts, the stimulation of tumor angiogenesis and the modulation of immune
      responses in the GI mucosa. A full understanding of these pathogenic mechanisms
      may help us to develop more effective therapies for GI disorders in the future. 

PMID- 24859305
TI  - Lean production of taste improved lipidic sodium benzoate formulations.
AB  - Sodium benzoate is a highly soluble orphan drug with unpleasant taste and high
      daily dose. The aim of this study was to develop a child appropriate,
      individually dosable, and taste masked dosage form utilizing lipids in melt
      granulation process and tableting. A saliva resistant coated lipid granule
      produced by extrusion served as reference product. Low melting hard fat was found
      to be appropriate as lipid binder in high-shear granulation. The resulting
      granules were compressed to minitablets without addition of other excipients.
      Compression to 2mm minitablets decreased the dissolved API amount within the
      first 2 min of dissolution from 33% to 23%. The Euclidean distances, calculated
      from electronic tongue measurements, were reduced, indicating an improved taste.
      The reference product showed a lag time in dissolution, which is desirable for
      taste masking. Although a lag time was not achieved for the lipidic minitablets,
      drug release in various food materials was reduced to 2%, assuming a suitable
      taste masking for oral sodium benzoate administration.

PMID- 24859306
TI  - Chitosan/glucose 1-phosphate as new stable in situ forming depot system for
      controlled drug delivery.
AB  - Chitosan (CS)-based thermosensitive solutions that turn into semi-solid hydrogels
      upon injection at body temperature have increasingly drawn attention over the
      last decades as an attractive new type of in situ forming depot (ISFD) drug
      delivery system. Despite the great potential of the standard CS/beta
      glycerophosphate (beta-GP) thermogelling solutions, their lack of stability over
      time at room temperature as well as at refrigerated conditions renders them
      unsuitable as ready-to-use drug product. In the present study, we investigated
      Glucose-1-Phosphate (G1-P) as an alternative gelling agent for improving the
      stability of CS-based ISFD solutions. The in vitro release performance of CS/G1-P
      formulations was assessed using several model compounds. Furthermore, the local
      tolerance of subcutaneously implanted CS/G1-P hydrogels was investigated by
      histological examination over three weeks. The thermogelling potential of CS/G1-P
      solutions, determined by rheology, is dependent on the polymer molecular weight
      (Mw) and concentration as well as on the G1-P concentration. Differential
      scanning calorimetry (DSC) measurements confirmed that sol/gel transition takes
      place at around body temperature and is not fully thermo-reversible. The long
      term storage stability was evaluated through the appearance, pH, viscosity and
      gelation time at 37 degrees C of the solution. The results emphasized an enhanced
      stability of the CS/G1-P system compared to the standard CS/beta-GP. CS solution
      with 0.40 mmol/g G1-P is stable for at least 9 months at 2-8 degrees C, versus
      less than 1 month when using beta-GP as gelling agent. Furthermore, the solution
      is easy to inject, as evidenced from injectability evaluation using 23-30 G
      needles. In vitro release experiments showed a sustained release over days to
      weeks for hydrophilic model compounds, demonstrating thereby that CS/G1-P may be
      suitable for the prolonged delivery of drugs. The inflammatory reaction observed
      in the tissue surrounding the hydrogel in rats was a typical foreign body
      reaction, similar to the one observed for CS/beta-GP hydrogels. These features
      confirm the potential of CS/G1-P solutions as an injectable ready-to-use in situ
      forming hydrogel.

PMID- 24859307
TI  - Performance of magnetic chitosan-alginate core-shell beads for increasing the
      bioavailability of a low permeable drug.
AB  - This work reports the synthesis and performance of magnetic chitosan-alginate
      core-shell beads for oral administration of small molecules in order to increase
      their bioavailability. For this purpose, we designed magnetic core-shell beads
      suitable for oral delivery that are resistant in acidic media (stomach pH),
      mucoadhesive, exhibit a superparamagnetic behavior and a very high entrapment
      efficiency. Ex vivo experiments were performed in Ussing chambers, to emphasize
      the effect of magnetic accumulation. The amount of drug permeated through the
      membrane exhibited a threefold increase with our novel drug delivery system.
      According to a correlation law, our ex vivo model showed that the adsorbed
      fraction (FA) in human is expected to reach 70% when using the magnetic retention
      system which is a great improvement when compared to the controls (FA=20%). 

PMID- 24859304
TI  - The burden of disease in rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a chronic inflammatory disease which, if left
      untreated, leads to functional disability, pain, reduced health-related quality
      of life and premature mortality. Between 0.5% and 1% of the population are
      affected worldwide, and between 25 and 50 new cases evolve in a population of
      100,000. Practically all patients with RA require initiation with disease
      modifying antirheumatic treatment to retard or stop progression, control disease
      manifestations and reduce the disease burden. If disease course is monitored with
      adjustment of medication, lifestyle factors, and exercise, as well as physical
      activity levels, co-morbidities may be prevented in the course of RA. During the
      last decade, major progress has been made in treating RA through early
      identification and treatment of the disease. Many patients still experience
      premature work disability and co-morbidities. For societies, the economic burden
      of RA is high in terms of direct and indirect costs, including modern drug
      treatment.

PMID- 24859308
TI  - Enteric pathogen-plant interactions: molecular connections leading to
      colonization and growth and implications for food safety.
AB  - Leafy green vegetables have been identified as a source of foodborne illnesses
      worldwide over the past decade. Human enteric pathogens, such as Escherichia coli
      O157:H7 and Salmonella, have been implicated in numerous food poisoning outbreaks
      associated with the consumption of fresh produce. An understanding of the
      mechanisms responsible for the establishment of pathogenic bacteria in or on
      vegetable plants is critical for understanding and ameliorating this problem as
      well as ensuring the safety of our food supply. While previous studies have
      described the growth and survival of enteric pathogens in the environment and
      also the risk factors associated with the contamination of vegetables, the
      molecular events involved in the colonization of fresh produce by enteric
      pathogens are just beginning to be elucidated. This review summarizes recent
      findings on the interactions of several bacterial pathogens with leafy green
      vegetables. Changes in gene expression linked to the bacterial attachment and
      colonization of plant structures are discussed in light of their relevance to
      plant-microbe interactions. We propose a mechanism for the establishment and
      association of enteric pathogens with plants and discuss potential strategies to
      address the problem of foodborne illness linked to the consumption of leafy green
      vegetables. 

PMID- 24859310
TI  - Inhibitory effects of ferrihydrite on a thermophilic methanogenic community.
AB  - The addition of ferrihydrite to methanogenic microbial communities obtained from
      a thermophilic anaerobic digester suppressed methanogenesis in a dose-dependent
      manner. The amount of reducing equivalents consumed by the reduction of iron was
      significantly smaller than that expected from the decrease in the production of
      CH4, which suggested that competition between iron-reducing microorganisms and
      methanogens was not the most significant cause for the suppression of
      methanogenesis. Microbial community analyses revealed that the presence of
      ferrihydrite markedly affected the bacterial composition, but not the archaeal
      composition. These results indicate that the presence of ferrihydrite directly
      and indirectly suppresses thermophilic methanogenesis. 

PMID- 24859309
TI  - The combination of functional metagenomics and an oil-fed enrichment strategy
      revealed the phylogenetic diversity of lipolytic bacteria overlooked by the
      cultivation-based method.
AB  - Metagenomic screening and conventional cultivation have been used to exploit
      microbial lipolytic enzymes in nature. We used an indigenous forest soil (NS) and
      oil-fed enriched soil (OS) as microbial and genetic resources. Thirty-four
      strains (17 each) of lipolytic bacteria were isolated from the NS and OS
      microcosms. These isolates were classified into the (sub)phyla
      Betaproteobacteria, Gammaproteobacteria, Firmicutes, and Actinobacteria, all of
      which are known to be the main microbial resources of commercially available
      lipolytic enzymes. Seven and 39 lipolytic enzymes were successfully retrieved
      from the metagenomic libraries of the NS and OS microcosms, respectively. The
      screening efficiency (a ratio of positive lipolytic clones to the total number of
      environmental clones) was markedly higher in the OS microcosm than in the NS
      microcosm. Moreover, metagenomic clones encoding the lipolytic enzymes associated
      with Alphaproteobacteria, Deltaproteobacteria, Acidobacteria, Armatimonadetes,
      and Planctomycetes and hitherto-uncultivated microbes were recovered from these
      libraries. The results of the present study indicate that functional metagenomics
      can be effectively used to capture as yet undiscovered lipolytic enzymes that
      have eluded the cultivation-based method, and these combined approaches may be
      able to provide an overview of lipolytic organisms potentially present in nature.

PMID- 24859311
TI  - Canopy-forming seaweeds in urchin-dominated systems in eastern Canada:
      structuring forces or simple prey for keystone grazers?
AB  - Models of benthic community dynamics for the extensively studied, shallow rocky
      ecosystems in eastern Canada emphasize kelp-urchin interactions. These models may
      bias the perception of factors and processes that structure communities, for they
      largely overlook the possible contribution of other seaweeds to ecosystem
      resilience. We examined the persistence of the annual, acidic (H2SO4), brown
      seaweed Desmarestia viridis in urchin barrens at two sites in Newfoundland
      (Canada) throughout an entire growth season (February to October). We also
      compared changes in epifaunal assemblages in D. viridis and other conspicuous
      canopy-forming seaweeds, the non-acidic conspecific Desmarestia aculeata and kelp
      Agarum clathratum. We show that D. viridis can form large canopies within the 2
      to-8 m depth range that represent a transient community state termed "Desmarestia
      bed". The annual resurgence of Desmarestia beds and continuous occurrence of D.
      aculeata and A. clathratum, create biological structure for major recruitment
      pulses in invertebrate and fish assemblages (e.g. from quasi-absent gastropods to
      >150,000 recruits kg(-1) D. viridis). Many of these pulses phase with temperature
      driven mass release of acid to the environment and die-off in D. viridis. We
      demonstrate experimentally that the chemical makeup of D. viridis and A.
      clathratum helps retard urchin grazing compared to D. aculeata and the highly
      consumed kelp Alaria esculenta. In light of our findings and related studies, we
      propose fundamental changes to the study of community shifts in shallow, rocky
      ecosystems in eastern Canada. In particular, we advocate the need to regard
      certain canopy-forming seaweeds as structuring forces interfering with top-down
      processes, rather than simple prey for keystone grazers. We also propose a novel,
      empirical model of ecological interactions for D. viridis. Overall, our study
      underscores the importance of studying organisms together with cross-scale
      environmental variability to better understand the factors and processes that
      shape marine communities.

PMID- 24859312
TI  - Protoporphyrin-IX fluorescence guided surgical resection in high-grade gliomas:
      The potential impact of human colour perception.
AB  - INTRODUCTION: Protoporphyrin-IX (Pp-IX) fluorescence had been used frequently in
      recent years to guide microsurgical resection of high-grade gliomas (HGG),
      particularly following the publication of a randomized controlled trial
      demonstrating its advantages. However, Pp-IX fluorescence is dependent upon the
      surgeons' eyes' perception of red fluorescent colour. This study was designed to
      evaluate human eye fluorescence perception and establish a fluorescence scale.
      MATERIALS AND METHODS: 20 of 108 pre-recorded images from intraoperative
      fluorescence of HGG were used to construct an 8-panel visual analogue
      fluorescence scale. The scale was validated by testing 56 participants with
      normal colour vision and three red-green colour-blind participants. For intra
      rater agreement ten participants were tested twice and for inter-observer
      reliability the whole cohort were tested. RESULTS: The intra- and inter-observer
      reliability of the scale in normal colour vision participants was excellent. The
      scale was less reliable in the violet-blue panels of the scale. Colour-blind
      participants were not able to distinguish between red fluorescence and blue
      violet colours. CONCLUSION: The 8-panel fluorescence scale is valid in
      differentiating red, pink and blue colours in a fluorescence surgical field among
      participants with normal colour perception and potentially useful to standardize
      fluorescence-guided surgery. However, colourblind surgeons should not use
      fluorescence-guided surgery.

PMID- 24859314
TI  - In vitro elution of vancomycin from biodegradable osteoconductive calcium
      phosphate-polycaprolactone composite beads for treatment of osteomyelitis.
AB  - In this work, osteoconductive composite materials comprising a large volume
      fraction of a bioresorbable calcium phosphate ceramic (CaP) and a smaller amount
      of a polycaprolactone polymer (PCL) were studied as a degradable antibiotic
      carrier material for treatment of osteomyelitis. Beads loaded with 1 and 4wt.%
      vancomycin were prepared by admixing dissolved drug to an in situ synthesized
      dicalcium phosphate (DCP)-PCL or solution-mixed beta-tricalcium phosphate
      (betaTCP)-PCL composite powder followed by high pressure consolidation of the
      blend at room temperature. Vancomycin release was measured in phosphate-buffered
      saline (PBS) at 37 degrees C. All the beads gradually released the drug over the
      period of 4-11weeks, depending on the composite matrix homogeneity and porosity.
      Mathematical modeling using the Peppas equation showed that vancomycin elution
      was diffusion controlled. The stability of the antibiotic after high pressure
      application at room temperature was demonstrated by high-performance liquid
      chromatography-mass spectrometry (HPLC-MS) studies and MIC testing. The
      preservation of the structure and activity of vancomycin during the processing of
      composite beads and its sustained in vitro release profile suggest that high
      pressure consolidated CaP-PCL beads may be useful in the treatment of chronic
      bone infections as resorbable delivery vehicles of vancomycin and even of
      thermally unstable drug substances. 

PMID- 24859313
TI  - Excreted/secreted Schistosoma mansoni venom allergen-like 9 (SmVAL9) modulates
      host extracellular matrix remodelling gene expression.
AB  - The Schistosoma mansoni venom allergen-like (SmVAL) protein family consists of 29
      members, each possessing a conserved alpha-beta-alpha sandwich tertiary feature
      called the Sperm-coating protein/Tpx-1/Ag5/PR-1/Sc7 (SCP/TAPS) domain. While the
      SmVALs have been found in both excretory/secretory (E/S) products and in
      intra/sub-tegumental (non-E/S) fractions, the role(s) of this family in
      host/parasite relationships or schistosome developmental processes remains poorly
      resolved. In order to begin quantifying SmVAL functional diversity or redundancy,
      dissecting the specific activity (ies) of individual family members is necessary.
      Towards this end, we present the characterisation of SmVAL9; a protein previously
      found enriched in both miracidia/sporocyst larval transformation proteins and in
      egg secretions. While our study confirms that SmVAL9 is indeed found in soluble
      egg products and miracidia/sporocyst larval transformation proteins, we find it
      to be maximally transcribed/translated in miracidia and subsequently down
      regulated during in vitro sporocyst development. SmVAL9 localisation within
      sporocysts appears concentrated in parenchymal cells/vesicles as well as
      associated with larval germinal cells. Furthermore, we demonstrate that egg
      derived SmVAL9 carries an N-linked glycan containing a schistosome-specific
      difucosyl element and is an immunogenic target during chronic murine
      schistosomiasis. Finally, we demonstrate that recombinant SmVAL9 affects the
      expression of extracellular matrix, remodelling matrix metalloproteinase (MMP)
      and tissue inhibitors of metalloproteinase (TIMP) gene products in both
      Biomphalaria glabrata embryonic cell (BgMMP1) and Mus musculus bone marrow
      derived macrophage (MmMMP2, MmMMP9, MmMMP12, MmMMP13, MmMMP14, MmMMP28, TIMP1 and
      TIMP2) in vitro cultures. These findings importantly suggest that
      excreted/secreted SmVAL9 participates in tissue reorganisation/extracellular
      matrix remodelling during intra-mammalian egg translocation, miracidia infection
      and intra-molluscan sporocyst development/migration.

PMID- 24859315
TI  - A spindle pole antigen gene MoSPA2 is important for polar cell growth of
      vegetative hyphae and conidia, but is dispensable for pathogenicity in
      Magnaporthe oryzae.
AB  - Spa2 is an important component of the multiprotein complex polarisome, which is
      involved in the establishment, maintenance, termination of polarized cell growth
      and is important for defining tip growth of filamentous fungi. In this study, we
      isolated an insertional mutant of the rice blast fungus Magnaporthe oryzae that
      formed smaller colony and conidia compared with the wild type. In the mutant, a
      spindle pole antigen gene MoSPA2 was disrupted by the integration of an exogenous
      plasmid. Targeted gene deletion and complementation assays demonstrated the gene
      disruption was responsible for the defects of the insertional mutant.
      Interestingly, the MoSpa2-GFP fusion protein was found to accumulate as a spot at
      hyphal tips, septa of hyphae and conidial tip cells where germ tubes are usually
      produced, but not in appressoria, infection hyphae or at the septa of conidia.
      Furthermore, the deletion mutants of MoSPA2 exhibited slower hyphal tip growth,
      more hyphal branches, and smaller size of conidial tip cells. However, MoSPA2 is
      not required for plant infection. These results indicate that MoSPA2 is required
      for vegetative hyphal growth and maintaining conidium morphology and that spotted
      accumulation of MoSpa2 is important for its functions during cell polar growth.

PMID- 24859316
TI  - Depletion of lamina-associated polypeptide 1 from cardiomyocytes causes cardiac
      dysfunction in mice.
AB  - We previously showed that striated muscle-selective depletion of lamina
      associated polypeptide 1 (LAP1), an integral inner nuclear membrane protein,
      leads to profound muscular dystrophy with premature death in mice. As LAP1 is
      also depleted in hearts of these mice, we examined their cardiac phenotype.
      Striated muscle-selective LAP1 knockout mice display ventricular systolic
      dysfunction with abnormal induction of genes encoding cardiomyopathy related
      proteins. To eliminate possible confounding effects due to skeletal muscle
      pathology, we generated a new mouse line in which LAP1 is deleted in a
      cardiomyocyte-selective manner. These mice had no skeletal muscle pathology and
      appeared overtly normal at 20 weeks of age. However, cardiac echocardiography
      revealed that they developed left ventricular systolic dysfunction and cardiac
      gene expression analysis revealed abnormal induction of cardiomyopathy-related
      genes. Our results demonstrate that LAP1 expression in cardiomyocytes is required
      for normal left ventricular function, consistent with a report of cardiomyopathy
      in a human subject with mutation in the gene encoding LAP1. 

PMID- 24859319
TI  - Design of novel camphane-based derivatives with antimycobacterial activity.
AB  - Although tuberculosis (TB) continues to be one of the leading infectious disease
      killers globally, it is curable and preventable. Despite the existence of safe,
      well tolerated and effective drugs used in the TB treatment, the interest in new
      entities, combinations and regimens increases during the last 10 years. Recently,
      we reported for a new class of anti-TB agents - camphane-based derivatives with
      nanomolar activity against Mycobacterium tuberculosis strains. The quantitative
      structure-activity relationship (QSAR) study on 12 compounds revealed several
      structural requirements for antimycobacterial activity: two hydrogen bond donors,
      two or three rings and no large branched substituents. Here, we describe the
      design of a set of nine novel camphane-based derivatives following these
      requirements. The compounds were synthesized and tested against M. tuberculosis
      strain H37Rv. Four of them showed activities in the nanomolar range,
      significantly higher than the activities in the initial set. The QSAR study based
      on all 21 derivatives pointed to two main structural requirements for anti-TB
      activity: two hydrogen bond donors and a side chain with aromatic ring. 

PMID- 24859318
TI  - Snx14 regulates neuronal excitability, promotes synaptic transmission, and is
      imprinted in the brain of mice.
AB  - Genomic imprinting describes an epigenetic process through which genes can be
      expressed in a parent-of-origin-specific manner. The monoallelic expression of
      imprinted genes renders them particularly susceptible to disease causing
      mutations. A large proportion of imprinted genes are expressed in the brain, but
      little is known about their functions. Indeed, it has proven difficult to
      identify cell type-specific imprinted genes due to the heterogeneity of cell
      types within the brain. Here we used laser capture microdissection of visual
      cortical neurons and found evidence that sorting nexin 14 (Snx14) is a neuronally
      imprinted gene in mice. SNX14 protein levels are high in the brain and
      progressively increase during neuronal development and maturation. Snx14
      knockdown reduces intrinsic excitability and severely impairs both excitatory and
      inhibitory synaptic transmission. These data reveal a role for monoallelic Snx14
      expression in maintaining normal neuronal excitability and synaptic transmission.

PMID- 24859317
TI  - Somato-motor inhibitory processing in humans: evidence from neurophysiology and
      neuroimaging.
AB  - Motor execution processing has been examined using an index of behavioral
      performance such as reaction times, kinetics, and kinematics. However,
      difficulties have been associated with the study of motor inhibitory processing
      because of the absence of actual behavioral performance. Therefore, non-invasive
      neurophysiological and neuroimaging methods including electroencephalography,
      magnetoencephalography, transcranial magnetic stimulation, and functional
      magnetic resonance imaging have been used to investigate neural processes in the
      central nervous system. We mainly reviewed research on somato-motor inhibitory
      processing based on data obtained by using these techniques, which can examine
      'when', 'where, and 'how' motor inhibition occurs in the brain. Although to date
      a number of studies have used these techniques separately, few studies have
      utilized them in a comprehensive manner. In this review, we provide evidence that
      combining neurophysiological and neuroimaging methods should contribute to our
      understanding of how executive and inhibitory functions are implemented. 

PMID- 24859321
TI  - Multiple hypoplastic duplicated urethral hydrodistension and simple end-to-end
      anastomosis to penoscrotal hypospadias: a novel technique.
AB  - Complete urethral duplication is a rare congenital genitourinary anomaly with
      various symptoms. Since anatomical place of urethra greatly varies between cases,
      surgical management of the patients is personalized according to the type of the
      duplication and requires a careful workup before planning for any intervention.
      In this case report, a 4-year-old boy with finding of complete proximal
      hypospadiac urethral duplication is presented with double-stream voiding. He was
      passing a normal stream of urine through the hypospadiac tract, while a thin
      stream came out from the normal meatal site. Examination revealed a hypoplastic
      orthotopic urethra with an accessory penoscrotal hypospadiac urethra. The patient
      was successfully managed with hydrodistension technique which was used to resolve
      the stricture of hypoplastic dorsal urethra followed by end-to-end anastomosis to
      penoscrotal hypospadias. This approach gives an insight that the technique could
      be possibly considered as a simple alternative to avoid proximal hypospadias
      repair which is comparatively a challenging surgical task. 

PMID- 24859320
TI  - Polyethylene glycol (PEG) linked to near infrared (NIR) dyes conjugated to
      chimeric anti-carcinoembryonic antigen (CEA) antibody enhances imaging of liver
      metastases in a nude-mouse model of human colon cancer.
AB  - We report here that polyethylene glycol (PEG) linked to near infrared dyes
      conjugated to chimeric mouse-human anti-carcinoembryonic antigen (CEA) antibody
      greatly improves imaging of liver metastases in a nude mouse model of colon
      cancer experimental metastases. PEGylated and non-PEGylated DyLight 650 and 750
      dyes were conjugated to the chimeric anti-CEA antibody. The dyes were initially
      injected intravenously into nude mice without tumors. Tissue biodistribution was
      determined by tissue sonication and analyzing tissue dye concentration profiles
      over time. PEGylated dyes had significantly lower accumulation in the liver (p =
      0.03 for the 650 dyes; p = 0.002 for the 750 dyes) compared to non-PEGylated
      dyes. In an experimental liver metastasis model of HT-29 colon cancer, PEGylated
      dyes conjugated to the anti-CEA antibody showed good labeling of metastatic
      tumors with high contrast between normal and malignant tissue which was not
      possible with the non-PEGylated dyes since there was so much non-specific
      accumulation in the liver. PEGylation of the DyLight 650 and 750 NIR dyes
      significantly altered tissue biodistribution, allowing brighter tissue labeling,
      decreased accumulation in normal organs, particularly the liver. This enabled
      high fidelity and high contrast imaging of liver metastases. 

PMID- 24859322
TI  - Effects of the recreational use of PDE5 inhibitors on the corpus cavernosum of
      young, healthy rats.
AB  - PURPOSE: PDE5 inhibitors are widely used for the treatment of erectile
      dysfunction. However, these drugs have recently become popular among men without
      erectile dysfunction as a means of enhancing sexual performance and improving
      sexual desire. The aim of this study was to investigate the histopathological and
      ultrastructural effects of PDE5 inhibitors on the corpus cavernosum in young,
      healthy male rats. METHODS: Twenty-four 4-month-old male rats were divided into
      four groups: group 1 was the control group, group 2 rats received sildenafil
      citrate, group 3 rats received vardenafil hydrochloride, and group 4 rats
      received tadalafil. All drugs were administered for 4 weeks. Penile tissue was
      collected for electron microscopy and tissue collagen measurements. Electron
      microscopic analysis indicated that the number of active fibroblasts and
      macrophages and the synthesis of new collagen fibers increased in treated rats.
      RESULTS: Cavernous tissue collagen levels were significantly higher in the
      sildenafil-, vardenafil-, and tadalafil-treated groups than in controls (46.16 +/
      4.9, 42.06 +/- 2.4, 41.07 +/- 2.4, and 29.20 +/- 3.3, respectively) (p < 0.001).
      CONCLUSIONS: Young men who use these drugs to enhance performance in the absence
      of erectile dysfunction may experience irreversible damage to the cavernosal
      tissue. However, more studies are needed to evaluate the molecular mechanisms by
      which PDE5 inhibitors affect the corpus cavernosum.

PMID- 24859323
TI  - Predominance of rotavirus G1[P8] genotype among under-five children with
      gastroenteritis in Mwanza, Tanzania.
AB  - We analyzed stool samples from underfives with gastroenteritis for rotavirus
      infection between January 2010 and June 2011. A total of 393 stool specimens were
      examined for rotavirus infection using enzyme-linked immunosorbent assay (ELISA).
      Hundred selected positive specimens were genotyped using multiplex polymerase
      chain reaction. Out of 393 underfives, 194 (49.4%) had rotavirus infection, with
      96.9% of infected underfives being <2 years. Underfives infected with rotavirus
      had prolonged hospital stay than those without rotavirus infection (P = 0.0001).
      G1 was the most predominant G type (59%) followed by G8 (13%) while P[8] was the
      most predominant P type (25%). In single-type infection, common G-P combinations
      were G1P[8] (24%) and G1P[6] (17%). Common mixed infections were G1/G8 (16%) and
      P4/P8 (13%). G1 genotype is common among underfives with gastroenteritis in
      Mwanza. Diversity of genotypes causing gastroenteritis in Mwanza necessitates a
      continuous surveillance after the introduction of RotaRix(r) vaccine. 

PMID- 24859324
TI  - 3-Hydroxypyrrolidine and (3,4)-dihydroxypyrrolidine derivatives: inhibition of
      rat intestinal alpha-glucosidase.
AB  - Thirteen pyrrolidine-based iminosugar derivatives have been synthesized and
      evaluated for inhibition of alpha-glucosidase from rat intestine. The compounds
      studied were the non-hydroxy, mono-hydroxy and dihydroxypyrrolidines. All the
      compounds were N-benzylated apart from one. Four of the compounds had a carbonyl
      group in the 2,5-position of the pyrrolidine ring. The most promising iminosugar
      was the trans-3,4-dihydroxypyrrolidine 5 giving an IC50 of 2.97+/-0.046 and a KI
      of 1.18 mM. Kinetic studies showed that the inhibition was of the mixed type, but
      predominantly competitive for all the compounds tested. Toxicological assay
      results showed that the compounds have low toxicity. Docking studies showed that
      all the compounds occupy the same region as the DNJ inhibitor on the enzyme
      binding site with the most active compounds establishing similar interactions
      with key residues. Our studies suggest that a rotation of ~90 degrees  of some
      compounds inside the binding pocket is responsible for the complete loss of
      inhibitory activity. Despite the fact that activity was found only in the mM
      range, these compounds have served as simple molecular tools for probing the
      structural features of the enzyme, so that inhibition can be improved in further
      studies.

PMID- 24859325
TI  - Gallic acid inhibits migration and invasion of SCC-4 human oral cancer cells
      through actions of NF-kappaB, Ras and matrix metalloproteinase-2 and -9.
AB  - Oral cancer is one of the major causes of mortality in humans and squamous cell
      carcinoma is the most common type of oral cancer. Gallic acid (GA) is a natural
      product that induces cell death through cell cycle arrest and induction of
      apoptosis. There is no available information on whether GA affects cell migration
      and invasion of human oral cancer cells. We determined if GA inhibited migration
      and invasion of SCC-4 (human squamous cell carcinoma) human oral cancer cells. GA
      significantly inhibited migration and invasion of SCC-4 cells based on results
      from the wound healing assay and Matrigel Cell Migration Assay and Invasion
      System. We also showed that GA significantly inhibited matrix metalloproteinase
      (MMP)-2 and MMP-9 activity. GA reduced protein levels of FAK, MEKK3, p-PERK, p
      p38, p-JNK1/2, p-ERK1/2, SOS1, RhoA, Ras, PKC, p-AKT(Thr308), PI3K, NF-kappaB
      p65, MMP-2 and MMP-9 in SCC-4 cells. Translocation of NF-kappaB and RhoA from the
      cytosol to the nucleus was reduced by GA in SCC-4 cells. In summary, GA inhibits
      migration and invasion of SCC-4 cells by inhibiting NF-kappaB expression causing
      suppression of MMP-2 and MMP-9 activity. GA may have potential as a therapeutic
      agent for the treatment of oral cancer.

PMID- 24859326
TI  - Coilin is rapidly recruited to UVA-induced DNA lesions and gamma-radiation
      affects localized movement of Cajal bodies.
AB  - Cajal bodies are important nuclear structures containing proteins that
      preferentially regulate RNA-related metabolism. We investigated the cell-type
      specific nuclear distribution of Cajal bodies and the level of coilin, a protein
      of Cajal bodies, in non-irradiated and irradiated human tumor cell lines and
      embryonic stem (ES) cells. Cajal bodies were localized in different nuclear
      compartments, including DAPI-poor regions, in the proximity of chromocenters, and
      adjacent to nucleoli. The number of Cajal bodies per nucleus was cell cycle
      dependent, with higher numbers occurring during G2 phase. Human ES cells
      contained a high coilin level in the nucleoplasm, but coilin-positive Cajal
      bodies were also identified in nuclei of mouse and human ES cells. Coilin, but
      not SMN, recognized UVA-induced DNA lesions, which was cell cycle-independent.
      Treatment with gamma-radiation reduced the localized movement of Cajal bodies in
      many cell types and GFP-coilin fluorescence recovery after photobleaching was
      very fast in nucleoplasm in comparison with GFP-coilin recovery in DNA lesions.
      By contrast, nucleolus-localized coilin displayed very slow fluorescence recovery
      after photobleaching, which indicates very slow rates of protein diffusion,
      especially in nucleoli of mouse ES cells. 

PMID- 24859327
TI  - The incidence of mismatch repair gene defects in colorectal liver metastases.
AB  - Knowledge of the molecular biology of primary colorectal cancer (CRC) has
      improved in recent years, and one reason for this is the identification of
      microsatellite instability (MSI), which occurs in up to 15% of sporadic CRC.
      However, less is known regarding the processes involved in colorectal liver
      metastases (CRLM). Increasing numbers of patients with CRLM are suitable for
      curative resection, so the identification of molecular markers may improve
      patient selection. The aim of the present study was to characterise the incidence
      of MSI in resected CRLM. Fifty-one sequentially resected CRLM specimens were
      selected. Clinicopathologic data was collated and immunohistochemistry for MLH1
      and MSH2 was performed on paraffin sections of the CRLM specimens. The
      association between abnormal staining and the clinicopathological data was
      examined. The median age of the subjects in the current study was 65 years, the
      average number of CRLM was 2 and the median overall survival time was 42.1 months
      post liver resection. None of the 50 resected specimens demonstrated abnormal
      staining for MLH1 or MSH2. Compared with the previously reported incidence of MSI
      in primary CRC, the low incidence of MSI in the current cohort of CRLM precludes
      its use as a marker for use in making clinical decisions regarding this
      condition. 

PMID- 24859328
TI  - Neural correlates of letter reversal in children and adults.
AB  - Children often make letter reversal errors when first learning to read and write,
      even for letters whose reversed forms do not appear in normal print. However, the
      brain basis of such letter reversal in children learning to read is unknown. The
      present study compared the neuroanatomical correlates (via functional magnetic
      resonance imaging) and the electrophysiological correlates (via event-related
      potentials or ERPs) of this phenomenon in children, ages 5-12, relative to young
      adults. When viewing reversed letters relative to typically oriented letters,
      adults exhibited widespread occipital, parietal, and temporal lobe activations,
      including activation in the functionally localized visual word form area (VWFA)
      in left occipito-temporal cortex. Adults exhibited significantly greater
      activation than children in all of these regions; children only exhibited such
      activation in a limited frontal region. Similarly, on the P1 and N170 ERP
      components, adults exhibited significantly greater differences between typical
      and reversed letters than children, who failed to exhibit significant differences
      between typical and reversed letters. These findings indicate that adults
      distinguish typical and reversed letters in the early stages of specialized brain
      processing of print, but that children do not recognize this distinction during
      the early stages of processing. Specialized brain processes responsible for early
      stages of letter perception that distinguish between typical and reversed letters
      may develop slowly and remain immature even in older children who no longer
      produce letter reversals in their writing. 

PMID- 24859330
TI  - Cerebral amyloid angiopathy revealed by rapidly progressing leptomeningeal
      lesions.

PMID- 24859329
TI  - Prolonged survival in adult neurofibromatosis type I patients with recurrent high
      grade gliomas treated with bevacizumab.
AB  - Astrocytic tumors, especially optic pathway pilocytic astrocytomas, are common in
      pediatric NF1 patients. High-grade gliomas (HGGs) appear to be rare in adult and
      pediatric NF1 patients. This is a series of five consecutive, adult NF1 patients
      with recurrent HGGs treated at The University of Texas MD Anderson Cancer Center.
      Four patients met consensus clinical criteria for NF1 and one patient had
      presumed segmental NF1. Three patients had glioblastomas, one gliosarcoma, and
      one progressive, enhancing optic pathway glioma which was not biopsied. Two
      tumors had molecular testing performed; both were IDH wild type and activating
      oncogene mutations (1 BRAFV600E and 1 PIK3CA mutation) were found in these
      tumors. All five patients received bevacizumab-containing regimens at tumor
      recurrence. The median number of 4-week cycles of bevacizumab was 20. All five
      patients experienced prolonged post-recurrence survival following bevacizumab
      treatment ranging from ten to 72 months. The median overall survival from HGG
      diagnosis was 72.6 months with three patients alive and progression free at last
      follow-up. Three out of five patients developed vascular complications leading to
      bevacizumab discontinuation. In this case series, adult NF1 patients with
      recurrent HGGs had prolonged, post-recurrence survival after treatment with
      bevacizumab-containing regimens. Based on these results, further study of
      antiangiogenic therapy in NF1 patients with HGGs and bevacizumab-response in
      sporadic HGG patients with NF1-mutated tumors is warranted.

PMID- 24859331
TI  - Tolvaptan treatment of severe stroke-like symptoms and bilateral subcortical
      diffusion restriction due to syndrome of inappropriate secretion of ADH after
      polytrauma.

PMID- 24859332
TI  - GD1b-specific antibodies may bind to complex of GQ1b and GM1, causing ataxia.
AB  - Monospecific IgG antibodies to GD1b ganglioside (GD1b-specific antibodies) have
      been found in patients with acute ataxic neuropathy and Guillain-Barre syndrome,
      but the association of the GD1b-specific antibodies with specific neurological
      conditions has yet to be established. We tested sera from more than 10,000
      patients with various neurological disorders, and found six sera, which contained
      IgG antibodies to GD1b, but not to LM1, GM1, GM1b, GD1a, GalNAc-GD1a, GT1a, GT1b
      and GQ1b. All six patients who carried GD1b-specific antibodies presented with
      acute onset of ataxia and monophasic course of the illness, of whom five
      demonstrated cerebellar-like ataxia. Four patients had antecedent symptoms of
      upper respiratory tract infection. The six patients demonstrated areflexia, and
      four complained of distal numbness. All the six patients who had the GD1b
      specific antibodies carried IgG antibodies to complex of GQ1b/GM1 and GT1a/GM1.
      GD1b-specific antibodies were significantly absorbed by GQ1b/GM1 and GT1a/GM1 and
      anti-GQ1b/GM1 and -GT1a/GM1 antibodies were absorbed by GD1b. In conclusion, the
      GD1b-specific antibodies, which recognizes GQ1b/GM1 or GT1a/GM1 complex, are
      associated with acute ataxia.

PMID- 24859334
TI  - A study of the energy absorption and exposure buildup factors of some anti
      inflammatory drugs.
AB  - Human radiation exposure is increasing due to radiation development in science
      and technology. The development of radioprotective agents is important for
      protecting patients from the side effects of radiotherapy and for protecting the
      public from unwanted irradiation. Radioprotective agents are used to reduce the
      damage caused by radiation in healthy tissues. There are several classes of
      radioprotective compounds that are under investigation. Analgesics and anti
      inflammatory compounds are being considered for treating or preventing the
      effects of damage due to radiation exposure, or for increasing the chance of
      survival after exposure to a high dose of radiation. In this study, we
      investigated the radioprotective effects of some analgesic and anti-inflammatory
      compounds by evaluating buildup factors. The gamma ray energy absorption (EABF)
      and exposure buildup factors (EBF) were calculated to select compounds in a 0.015
      15 MeV energy region up to a penetration depth of 40 mfp (mean free path).
      Variations of EABF and EBF with incident photon energy and penetration depth
      elements were also investigated. Significant variations in both EABF and EBF
      values were observed for several compounds at the moderate energy region. At
      energies below 0.15 MeV, EABF and EBF values increased with decreasing equivalent
      atomic number (Z(eq)) of the samples. In addition, EABF and EBF were the largest
      for ibuprofen, aspirin, paracetamol, naproxen and ketoprofen at 0.05 and 0.06
      MeV, respectively, and the EABF value was 0.1 MeV for aceclofenac. From these
      results, we concluded that the buildup of photons is less for aceclofenac
      compared to other materials.

PMID- 24859333
TI  - Non-thermal atmospheric plasmas in dental restoration: improved resin adhesive
      penetration.
AB  - OBJECTIVE: To investigate the influence of non-thermal plasma treatment on the
      penetration of a model dental adhesive into the demineralized dentine. METHODS:
      Prepared dentine surfaces were conditioned with Scotchbond Universal etchant for
      15s and sectioned equally perpendicular to the etched surfaces. The separated
      halves were randomly selected for treatment with an argon plasma brush (input
      current 6mA, treatment time 30s) or gentle argon air blowing (treatment time 30s,
      as control). The plasma-treated specimens and control specimens were applied with
      a model adhesive containing 2,2-bis[4-(2-hydroxy-3-methacryloxypropoxy) phenyl]
      propane (BisGMA) and 2-hydroxyethyl methacrylate (HEMA) (mass ratio of 30/70),
      gently air-dried for 5s, and light-cured for 20s. Cross-sectional specimens were
      characterized using micro-Raman spectral mapping across the dentine,
      adhesive/dentine interface, and adhesive layer at 1-MUm spatial resolution. SEM
      was also employed to examine the adhesive/dentine interfacial morphology.
      RESULTS: The micro-Raman result disclosed that plasma treatment significantly
      improved the penetration of the adhesive, evidenced by the apparently higher
      content of the adhesive at the adhesive/dentine interface as compared to the
      control. Specifically, the improvement of the adhesive penetration using plasma
      technique was achieved by dramatically enhancing the penetration of hydrophilic
      monomer (HEMA), while maintaining the penetration of hydrophobic monomer
      (BisGMA). Morphological observation at the adhesive/dentine interface using SEM
      also confirmed the improved adhesive penetration. The results further suggested
      that plasma treatment could benefit polymerization of the adhesive, especially in
      the interface region. CONCLUSION: The significant role of the non-thermal plasma
      brush in improving the adhesive penetration into demineralized dentine has been
      demonstrated. The results obtained may offer a better prospect of using plasma in
      dental restoration to optimize adhesion between tooth substrate and restorative
      materials.

PMID- 24859336
TI  - Inter-ring communication is dispensable in the reaction cycle of group II
      chaperonins.
AB  - Chaperonins are ubiquitous molecular chaperones with the subunit molecular mass
      of 60kDa. They exist as double-ring oligomers with central cavities. An ATP
      dependent conformational change of the cavity induces the folding of an unfolded
      protein that is captured in the cavity. In the group I chaperonins, which are
      present in eubacteria and eukaryotic organelles, inter-ring communication takes
      important role for the reaction cycle. However, there has been limited study on
      the inter-ring communication in the group II chaperonins that exist in archaea
      and the eukaryotic cytosol. In this study, we have constructed the asymmetric
      ring complex of a group II chaperonin using circular permutated covalent mutants.
      Although one ring of the asymmetric ring complex lacks ATPase or ATP binding
      activity, the other wild-type ring undergoes an ATP-dependent conformational
      change and maintains protein-folding activity. The results clearly demonstrate
      that inter-ring communication is dispensable in the reaction cycle of group II
      chaperonins. 

PMID- 24859335
TI  - APOBEC3G inhibits HIV-1 RNA elongation by inactivating the viral trans-activation
      response element.
AB  - Deamination of cytidine residues in viral DNA is a major mechanism by which
      APOBEC3G (A3G) inhibits vif-deficient human immunodeficiency virus type 1 (HIV-1)
      replication. dC-to-dU transition following RNase-H activity leads to viral cDNA
      degradation, production of non-functional proteins, formation of undesired stop
      codons and decreased viral protein synthesis. Here, we demonstrate that A3G
      provides an additional layer of defense against HIV-1 infection dependent on
      inhibition of proviral transcription. HIV-1 transcription elongation is regulated
      by the trans-activation response (TAR) element, a short stem-loop RNA structure
      required for elongation factors binding. Vif-deficient HIV-1-infected cells
      accumulate short viral transcripts and produce lower amounts of full-length HIV-1
      transcripts due to A3G deamination of the TAR apical loop cytidine, highlighting
      the requirement for TAR loop integrity in HIV-1 transcription. We further show
      that free single-stranded DNA (ssDNA) termini are not essential for A3G activity
      and a gap of CCC motif blocked with juxtaposed DNA or RNA on either or 3'+5' ends
      is sufficient for A3G deamination. These results identify A3G as an efficient
      mutator and that deamination of (-)SSDNA results in an early block of HIV-1
      transcription.

PMID- 24859337
TI  - Long-range enhancers regulating Myc expression are required for normal facial
      morphogenesis.
AB  - Cleft lip with or without cleft palate (CL/P) is one of the most common
      congenital malformations observed in humans, with 1 occurrence in every 500-1,000
      births. A 640-kb noncoding interval at 8q24 has been associated with increased
      risk of non-syndromic CL/P in humans, but the genes and pathways involved in this
      genetic susceptibility have remained elusive. Using a large series of
      rearrangements engineered over the syntenic mouse region, we show that this
      interval contains very remote cis-acting enhancers that control Myc expression in
      the developing face. Deletion of this interval leads to mild alteration of facial
      morphology in mice and, sporadically, to CL/P. At the molecular level, we
      identify misexpression of several downstream genes, highlighting combined impact
      on the craniofacial developmental network and the general metabolic capacity of
      cells contributing to the future upper lip. This dual molecular etiology may
      account for the prominent influence of variants in the 8q24 region on human
      facial dysmorphologies. 

PMID- 24859338
TI  - Recurrent PAX3-MAML3 fusion in biphenotypic sinonasal sarcoma.
AB  - Biphenotypic sinonasal sarcoma (SNS) is a newly described tumor of the nasal and
      paranasal areas. Here we report a recurrent chromosomal translocation in SNS,
      t(2;4)(q35;q31.1), resulting in a PAX3-MAML3 fusion protein that is a potent
      transcriptional activator of PAX3 response elements. The SNS phenotype is
      characterized by aberrant expression of genes involved in neuroectodermal and
      myogenic differentiation, closely simulating the developmental roles of PAX3. 

PMID- 24859339
TI  - Brain-expressed exons under purifying selection are enriched for de novo
      mutations in autism spectrum disorder.
AB  - A universal challenge in genetic studies of autism spectrum disorders (ASDs) is
      determining whether a given DNA sequence alteration will manifest as disease.
      Among different population controls, we observed, for specific exons, an inverse
      correlation between exon expression level in brain and burden of rare missense
      mutations. For genes that harbor de novo mutations predicted to be deleterious,
      we found that specific critical exons were significantly enriched in individuals
      with ASD relative to their siblings without ASD (P < 1.13 * 10(-38); odds ratio
      (OR) = 2.40). Furthermore, our analysis of genes with high exonic expression in
      brain and low burden of rare mutations demonstrated enrichment for known ASD
      associated genes (P < 3.40 * 10(-11); OR = 6.08) and ASD-relevant fragile-X
      protein targets (P < 2.91 * 10(-157); OR = 9.52). Our results suggest that brain
      expressed exons under purifying selection should be prioritized in genotype
      phenotype studies for ASD and related neurodevelopmental conditions. 

PMID- 24859340
TI  - Identification of recurrent SMO and BRAF mutations in ameloblastomas.
AB  - Here we report the discovery of oncogenic mutations in the Hedgehog and mitogen
      activated protein kinase (MAPK) pathways in over 80% of ameloblastomas, locally
      destructive odontogenic tumors of the jaw, by genomic analysis of archival
      material. Mutations in SMO (encoding Smoothened, SMO) are common in
      ameloblastomas of the maxilla, whereas BRAF mutations are predominant in tumors
      of the mandible. We show that a frequently occurring SMO alteration encoding
      p.Leu412Phe is an activating mutation and that its effect on Hedgehog-pathway
      activity can be inhibited by arsenic trioxide (ATO), an anti-leukemia drug
      approved by the US Food and Drug Administration (FDA) that is currently in
      clinical trials for its Hedgehog-inhibitory activity. In a similar manner,
      ameloblastoma cells harboring an activating BRAF mutation encoding p.Val600Glu
      are sensitive to the BRAF inhibitor vemurafenib. Our findings establish a new
      paradigm for the diagnostic classification and treatment of ameloblastomas. 

PMID- 24859342
TI  - Regional changes in the sequence of cotton leaf curl multan betasatellite.
AB  - Cotton leaf curl disease (CLCuD) in Pakistan and northwestern India is caused by
      monopartite begomoviruses in association with an essential, disease-specific
      satellite, Cotton leaf curl Multan betasatellite (CLCuMB). Following a recent
      upsurge in CLCuD problems in Sindh province (southern Pakistan), sequences of
      clones of CLCuMB were obtained from Sindh and Punjab province (central Pakistan),
      where CLCuD has been a problem since the mid-1980s. The sequences were compared
      to all sequences of CLCuMB available in the databases. Analysis of the sequences
      shows extensive sequence variation in CLCuMB, most likely resulting from
      recombination. The range of sequence variants differ between Sindh, the Punjab
      and northwestern India. The possible significance of the findings with respect to
      movement of the CLCuD between the three regions is discussed. Additionally, the
      lack of sequence variation within the only coding sequence of CLCuMB suggests
      that the betasatellite is not involved in resistance breaking which became a
      problem after 2001 in the Punjab and subsequently also in northwestern India. 

PMID- 24859343
TI  - Development and application of quantitative detection method for viral
      hemorrhagic septicemia virus (VHSV) genogroup IVa.
AB  - Viral hemorrhagic septicemia virus (VHSV) is a problematic pathogen in olive
      flounder (Paralichthys olivaceus) aquaculture farms in Korea. Thus, it is
      necessary to develop a rapid and accurate diagnostic method to detect this virus.
      We developed a quantitative RT-PCR (qRT-PCR) method based on the nucleocapsid (N)
      gene sequence of Korean VHSV isolate (Genogroup IVa). The slope and R2 values of
      the primer set developed in this study were -0.2928 (96% efficiency) and 0.9979,
      respectively. Its comparison with viral infectivity calculated by traditional
      quantifying method (TCID50) showed a similar pattern of kinetic changes in vitro
      and in vivo. The qRT-PCR method reduced detection time compared to that of
      TCID50, making it a very useful tool for VHSV diagnosis.

PMID- 24859341
TI  - The DNA damage response induced by infection with human cytomegalovirus and other
      viruses.
AB  - Viruses use different strategies to overcome the host defense system. Recent
      studies have shown that viruses can induce DNA damage response (DDR). Many of
      these viruses use DDR signaling to benefit their replication, while other viruses
      block or inactivate DDR signaling. This review focuses on the effects of DDR and
      DNA repair on human cytomegalovirus (HCMV) replication. Here, we review the DDR
      induced by HCMV infection and its similarities and differences to DDR induced by
      other viruses. As DDR signaling pathways are critical for the replication of many
      viruses, blocking these pathways may represent novel therapeutic opportunities
      for the treatment of certain infectious diseases. Lastly, future perspectives in
      the field are discussed. 

PMID- 24859345
TI  - Relaxed selection causes microevolution of seawater osmoregulation and gene
      expression in landlocked Alewives.
AB  - Ecological transitions from marine to freshwater environments have been important
      in the creation of diversity among fishes. Evolutionary changes associated with
      these transitions likely involve modifications of osmoregulatory function. In
      particular, relaxed selection on hypo-osmoregulation should strongly affect
      animals that transition into novel freshwater environments. We used populations
      of the Alewife (Alosa pseudoharengus) to study evolutionary shifts in hypo
      osmoregulatory capacity and ion regulation associated with freshwater
      transitions. Alewives are ancestrally anadromous, but multiple populations in
      Connecticut have been independently restricted to freshwater lakes; these
      landlocked populations complete their entire life cycle in freshwater. Juvenile
      landlocked and anadromous Alewives were exposed to three salinities (1, 20 and 30
      ppt) in small enclosures within the lake. We detected strong differentiation
      between life history forms: landlocked Alewives exhibited reduced seawater
      tolerance and hypo-osmoregulatory performance compared to anadromous Alewives.
      Furthermore, gill Na(+)/K(+)-ATPase activity and transcription of genes for
      seawater osmoregulation (NKCC-Na(+)/K(+)/2Cl(-) cotransporter and CFTR-cystic
      fibrosis transmembrane conductance regulator) exhibited reduced responsiveness to
      seawater challenge. Our study demonstrates that adaptations of marine-derived
      species to completely freshwater life cycles involve partial loss of seawater
      osmoregulatory performance mediated through changes to ion regulation in the
      gill. 

PMID- 24859344
TI  - Immunogenetic factors affecting susceptibility of humans and rodents to
      hantaviruses and the clinical course of hantaviral disease in humans.
AB  - We reviewed the associations of immunity-related genes with susceptibility of
      humans and rodents to hantaviruses, and with severity of hantaviral diseases in
      humans. Several class I and class II HLA haplotypes were linked with severe or
      benign hantavirus infections, and these haplotypes varied among localities and
      hantaviruses. The polymorphism of other immunity-related genes including the C4A
      gene and a high-producing genotype of TNF gene associated with severe PUUV
      infection. Additional genes that may contribute to disease or to PUUV infection
      severity include non-carriage of the interleukin-1 receptor antagonist (IL-1RA)
      allele 2 and IL-1beta (-511) allele 2, polymorphisms of plasminogen activator
      inhibitor (PAI-1) and platelet GP1a. In addition, immunogenetic studies have been
      conducted to identify mechanisms that could be linked with the
      persistence/clearance of hantaviruses in reservoirs. Persistence was associated
      during experimental infections with an upregulation of anti-inflammatory
      responses. Using natural rodent population samples, polymorphisms and/or
      expression levels of several genes have been analyzed. These genes were selected
      based on the literature of rodent or human/hantavirus interactions (some Mhc
      class II genes, Tnf promoter, and genes encoding the proteins TLR4, TLR7, Mx2 and
      beta3 integrin). The comparison of genetic differentiation estimated between bank
      vole populations sampled over Europe, at neutral and candidate genes, has allowed
      to evidence signatures of selection for Tnf, Mx2 and the Drb Mhc class II genes.
      Altogether, these results corroborated the hypothesis of an evolution of
      tolerance strategies in rodents. We finally discuss the importance of these
      results from the medical and epidemiological perspectives. 

PMID- 24859346
TI  - An ELISA method to compute endpoint titers to Epstein-Barr virus and
      cytomegalovirus: application to population-based studies.
AB  - Indirect fluorescence analysis (IFA), the gold standard for determining
      herpesvirus antibody titers, is labor-intensive and poorly suited for large
      population-based studies. The enzyme-linked immunosorbent assay (ELISA) is used
      widely for measuring antiviral antibodies but also suffers drawbacks such as
      reduced specificity and the qualitative nature of the results due to limited
      interpretation of the optical density (OD) units. This paper describes a method
      to titer herpesvirus antibodies using microplates coated with virally-infected
      cells in which a standard curve, derived from IFA-scored samples, allowed OD
      units to be converted into titers. A LOOKUP function was created in order to
      report the data as traditional IFA-based (i.e., 2-fold) titers. The modified
      ELISA correlated significantly with IFA and was subsequently used to compute
      endpoint antibody titers to Epstein-Barr virus (EBV)-virus capsid antigen (VCA)
      and cytomegalovirus (CMV) in blood samples taken from 398 pregnant Hispanic
      women. Four women were EBV negative (1%), while 58 women were CMV negative
      (14.6%). EBV VCA antibody titers were significantly higher than CMV antibody
      titers (p<0.001). This method allows titering of herpesvirus antibodies by ELISA
      suitable for large population-based studies. In addition, the LOOKUP table
      enables conversion from OD-derived titers into 2-fold titers for comparison of
      results with other studies.

PMID- 24859347
TI  - The involvement of NFAT transcriptional activity suppression in SIRT1-mediated
      inhibition of COX-2 expression induced by PMA/Ionomycin.
AB  - SIRT1, a class III histone deacetylase, acts as a negative regulator for many
      transcription factors, and plays protective roles in inflammation and
      atherosclerosis. Transcription factor nuclear factor of activated T cells (NFAT)
      has been previously shown to play pro-inflammatory roles in endothelial cells.
      Inhibition of NFAT signaling may be an attractive target to regulate inflammation
      in atherosclerosis. However, whether NFAT transcriptional activity is suppressed
      by SIRT1 remains unknown. In this study, we found that SIRT1 suppressed NFAT
      mediated transcriptional activity. SIRT1 interacted with NFAT, and the NHR and
      RHR domains of NFAT mediated the interaction with SIRT1. Moreover, we found that
      SIRT1 primarily deacetylated NFATc3. Adenoviral over-expression of SIRT1
      suppressed PMA and calcium ionophore Ionomycin (PMA/Io)-induced COX-2 expression
      in human umbilical vein endothelial cells (HUVECs), while SIRT1 RNAi reversed the
      effects in HUVECs. Moreover, inhibition of COX-2 expression by SIRT1 in PMA/Io
      treated HUVECs was largely abrogated by inhibiting NFAT activation. Furthermore,
      SIRT1 inhibited NFAT-induced COX-2 promoter activity, and reduced NFAT binding to
      the COX-2 promoter in PMA/Io-treated HUVECs. These results suggest that
      suppression of NFAT transcriptional activity is involved in SIRT1-mediated
      inhibition of COX-2 expression induced by PMA/Io, and that the negative
      regulatory mechanisms of NFAT by SIRT1 may contribute to its anti-inflammatory
      effects in atherosclerosis. 

PMID- 24859349
TI  - A novel COX-independent mechanism of sulindac sulfide involves cleavage of
      epithelial cell adhesion molecule protein.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) are extensively used over the
      counter to treat headaches and inflammation as well as clinically to prevent
      cancer among high-risk groups. The inhibition of cyclooxygenase (COX) activity by
      NSAIDs plays a role in their anti-tumorigenic properties. NSAIDs also have COX
      independent activity which is not fully understood. In this study, we report a
      novel COX-independent mechanism of sulindac sulfide (SS), which facilitates a
      previously uncharacterized cleavage of epithelial cell adhesion molecule (EpCAM)
      protein. EpCAM is a type I transmembrane glycoprotein that has been implemented
      as an over-expressed oncogene in many cancers including colon, breast, pancreas,
      and prostate. We found EpCAM to be down-regulated by SS in a manner that is
      independent of COX activity, transcription regulation, de novo protein synthesis,
      and proteasomal degradation pathway. Our findings clearly demonstrate that SS
      drives cleavage of the extracellular portion of EpCAM near the N-terminus. This
      SS driven cleavage is blocked by a deleting amino acids 55-81 as well as simply
      mutating arginine residues at positions 80 and 81 to alanine of EpCAM.
      Proteolysis of EpCAM by SS may provide a novel mechanism by which NSAIDs affect
      anti-tumorigenesis at the post-translational level. 

PMID- 24859350
TI  - Microfilament regulatory protein MENA increases activity of RhoA and promotes
      metastasis of hepatocellular carcinoma.
AB  - Mammalian enabled (MENA), usually known as a direct regulator of microfilament
      polymerization and bundling, promotes metastasis in various cancers. Here we
      focus on the role of MENA in hepatocellular carcinoma (HCC) metastasis and the
      relevant mechanism from the view of RhoA activity regulation. By HCC tissue
      microarray analysis, we found that MENA expression was positively associated with
      satellite lesions (P<0.01) and vascular invasion (P<0.01). Cases with membrane
      reinforcement of MENA staining in HCC tissues had significantly higher rates of
      early recurrence in the intermediate MENA expression group. Knockdown of MENA
      significantly suppressed HCC cell migration and invasion in vitro, as well as
      their intrahepatic and distant metastasis in vivo. Knockdown of MENA also
      decreased filopodia and stress fibers in SMMC-7721 cells. Furthermore, a decrease
      of RhoA activity was detected by a pull-down assay in SMMC-7721-shMENA cells. The
      ROCK inhibitor, Y-27632, suppressed migration of both MENA knockdown SMMC-7721
      cells and control cells, but diminished their difference. Thus, our findings
      suggest that MENA promotes HCC cell motility by activating RhoA. 

PMID- 24859348
TI  - High-throughput sequencing in mitochondrial DNA research.
AB  - Next-generation sequencing, also known as high-throughput sequencing, has greatly
      enhanced researchers' ability to conduct biomedical research on all levels.
      Mitochondrial research has also benefitted greatly from high-throughput
      sequencing; sequencing technology now allows for screening of all 16,569 base
      pairs of the mitochondrial genome simultaneously for SNPs and low level
      heteroplasmy and, in some cases, the estimation of mitochondrial DNA copy number.
      It is important to realize the full potential of high-throughput sequencing for
      the advancement of mitochondrial research. To this end, we review how high
      throughput sequencing has impacted mitochondrial research in the categories of
      SNPs, low level heteroplasmy, copy number, and structural variants. We also
      discuss the different types of mitochondrial DNA sequencing and their pros and
      cons. Based on previous studies conducted by various groups, we provide
      strategies for processing mitochondrial DNA sequencing data, including assembly,
      variant calling, and quality control. 

PMID- 24859351
TI  - Effect of early oral feeding on short-term outcome of patients receiving
      laparoscopic distal gastrectomy: a retrospective cohort study.
AB  - BACKGROUND: To evaluate the effect of early oral feeding on postoperative short
      term outcome of gastric cancer patients receiving laparoscopic distal
      gastrectomy. METHODS: From Oct 1, 2011 to Mar 1, 2013, 84 consecutive patients
      with gastric cancer were involved in this retrospective study. Patients received
      either early oral feeding (early feeding group) or not (control group) after
      laparoscopic distal gastrectomy. Details concerning the postoperative outcomes
      and the quality of life questionnaires were collected and compared. RESULTS:
      Totally 40 patients were involved in the early feeding group and 44 in the
      control group. Demographic data were comparable in both groups. The duration of
      hospital stay (6.28 +/- 1.26 VS 7.69 +/- 1.53, P = 0.048) and time until flatus
      (2.06 +/- 1.47 VS 3.56 +/- 1.04, P = 0.044) in early feeding group were
      significantly less than that in control group. Furthermore, the score of fatigue
      scale in early feeding group on the seventh postoperative day was significantly
      less than that in control group (33.9 +/- 12.1 VS 45.1 +/- 10.7, P = 0.041).
      CONCLUSIONS: Early oral feeding could lead to a significant improvement of the
      short-term benefits for patients receiving laparoscopic distal gastrectomy.

PMID- 24859352
TI  - How and how much do endoscopy professionals protect themselves against infection?
AB  - PURPOSE: It is aimed to identify, the educations given to professionals working
      in endoscopy units against infectious risks during the endoscopic procedures and
      awareness of professionals for protection from these infections. MATERIAL AND
      METHOD: After obtaining the required ethic committee permissions, 50 physicians
      and 34 nurses, working in the endoscopy units of three university and one
      training and research hospital, were included in this study. A survey with 37
      questions, prepared in accordance with the literature was applied to the
      participating endoscopist (E) and endoscopy nurses (EN). SPSS (Statistical
      Package for Social Sciences) for Windows 16.0 program was used for statistical
      evaluation of the obtained data. FINDINGS: Forty-four (52%) of the subjects were
      female and 40 (48%) were male, and their average age was 39 (+/-6.82) years. When
      trainings on endoscopy of E and EN were evaluated, it was found that 44% (n = 37)
      of them precise an endoscopy course on endoscopy training, %56 (n = 47) received
      no training and they learned through master/apprentice system. Furthermore, it
      was found that 65% (n = 55) of the E and EN received no training on universal
      precautions procedures, infection and risks endoscopic procedures and only 35% (n
      = 29) received a specific course or on-the-job training. Nevertheless, rates of
      wearing protective gowns and gloves were high both for E and EN; but rate of
      other precautions such as wearing mask, using special gloves and face shields
      were found to be low. It was found that the rate of "receiving an education on
      endoscopy" for E was significantly higher than that of EN (p < 0001). The rate of
      reporting emergency situations such as contact with blood/body fluids or
      percutaneous injuries and the rate of taking universal precautions of EN who
      received an education, was statistically higher than that of EN who did not (p <
      0.001 and p < 0008). RESULTS: As a result of our investigation, it was determined
      that the endoscopists and endoscopy nurses did not effectively apply the
      universal precautions against infectious risks faced during endoscopic procedures
      and did not receive the basic trainings. The professionals who received training
      were more responsive for this issue. According to our results, organizing
      continuous training programs through endoscopy professionals is necessary to
      provide the universal precautions of avoiding exposure to blood and body fluids.

PMID- 24859353
TI  - Mavacoxib and meloxicam for canine osteoarthritis: a randomised clinical
      comparator trial.
AB  - NSAIDs are the cornerstone of medical management of canine osteoarthritis (OA).
      Meloxicam is a daily-administered NSAID widely available in a liquid formulation
      and manufacturer's summary of product characteristics (SPC) advise that it is
      given at the lowest effective dose. Mavacoxib is a long-acting NSAID given as a
      monthly tablet. This study compares these drugs in the management of canine OA.
      In all, 111 dogs with OA of the elbow, hip or stifle were randomly assigned to
      receive one of these NSAIDs for a 12-week period, and to administer them as per
      the manufacturer's SPC. Outcomes, including ground reaction forces and three
      validated clinical metrology instruments, were measured at baseline, 6 and 12
      weeks. Improvements were seen in all outcome measures for both groups to a
      similar degree, and adverse events occurred at a similar rate. There were
      significant improvements in outcome measures from week 6 to week 12, as well as
      from baseline. Long-term meloxicam dose was more important than recent dose.
      Clinical efficacy and adverse event rates are similar for meloxicam and mavacoxib
      when administered as per their UK SPC. This is relevant information for
      veterinary surgeons when prescribing NSAID treatment for canine OA.

PMID- 24859355
TI  - Sodium arsenite induces ROS-dependent autophagic cell death in pancreatic beta
      cells.
AB  - Inorganic arsenic is a worldwide environmental pollutant. Inorganic arsenic's
      positive relationship with the incidence of type 2 diabetes mellitus arouses
      concerns associated with its etiology in diabetes among the general human
      population. In this study, the inhibitor of autophagosome formation, 3
      methyladenine, protected the cells against sodium arsenite cytotoxicity, and the
      autophagy stimulator rapamycin further decreased the cell viability of sodium
      arsenite-treated INS-1 cells. These finding suggested the hypothesis that
      autophagic cell death contributed to sodium arsenite-induced cytotoxicity in INS
      1 cells. Sodium arsenite increased the autophagosome-positive puncta in INS-1
      cells observed under a fluorescence microscope, and this effect was confirmed by
      the elevated LC3-II levels detected through Western blot. The LC3 turnover assay
      indicated that the accumulation of autophagosomes in the arsenite-treated INS-1
      cells was due to increased formation rather than impaired degradation. The
      pretreatment of INS-1 cells with the ROS inhibitor NAC reduced autophagosome
      formation and reversed the sodium arsenite cytotoxicity, indicating that sodium
      arsenite-induced autophagic cell death was ROS-dependent. In summary, the precise
      molecular mechanisms through which arsenic is related to diabetes have not been
      completely elucidated, but the ROS-dependent autophagic cell death of pancreatic
      beta-cells described in this study may help to elucidate the underlying
      mechanism. 

PMID- 24859356
TI  - The effect of dalteparin versus unfractionated heparin on the levels of troponin
      I and creatine kinase isoenzyme MB in elective percutaneous coronary
      intervention: a multicenter study.
AB  - BACKGROUND: The aim of this study was to investigate the safety and efficacy of
      dalteparin during an elective percutaneous coronary intervention (PCI) procedure
      in a large cohort. MATERIALS AND METHODS: In this prospective, randomized, open
      label design study, 733 patients undergoing elective PCI were divided into an
      unfractionated heparin group (group 1, 323 patients) or a dalteparin group (group
      2, 410 patients). Blood samples were collected before and 18-24 h after the PCI
      procedure to determine the serum levels of cardiac troponin I (cTnI) and creatine
      kinase isoenzyme MB. Major adverse cardiac events (MACEs) and bleeding events
      during hospitalization were also recorded. Patients with an increased level of
      serum cTnI before PCI were excluded from the study. RESULTS: After PCI, the cTnI
      values were greater than three times the upper limit of normal in 43 cases
      (13.3%) in group 1 and 52 cases (12.7%) in group 2, without a statistically
      significant difference between the two groups (P=0.801). An increased creatine
      kinase isoenzyme MB level of greater than two times the upper limit of normal was
      found in 10 cases (3.1%) in group 1 and 12 cases (2.9%) in group 2, without a
      statistically significant difference between the two groups (P=0.894).
      Postoperative bleeding was observed in nine patients (2.8%) in group 1 and six
      patients (1.5%) in group 2. Postoperative MACEs were observed in two patients
      (0.6%) in group 1 and two patients (0.5%) in group 2. There were no significant
      differences between the two groups with respect to bleeding events or MACEs.
      CONCLUSION: Our study showed that dalteparin might be as effective and safe as
      unfractionated heparin for anticoagulation during elective PCI.

PMID- 24859357
TI  - Variation in the documentation of findings in pediatric voiding cystourethrogram.
AB  - BACKGROUND: Few standards exist for reporting results of voiding cystourethrogram
      (VCUG). OBJECTIVE: To assess the variation in reporting of VCUG findings from
      different facilities using a standardized assessment tool. MATERIALS AND METHODS:
      VCUG reports were evaluated for demographic, technical, anatomical and functional
      information. Reports were categorized by age, gender, indication and vesicouretal
      reflux (VUR) status. Institutions were classified as a free-standing pediatric
      hospital (n = 3), pediatric hospital within a hospital (n = 11), or non-pediatric
      facility (n = 24) and reports were classified as having been read by a pediatric
      radiologist or not. Each category of outside reports (n = 152) was randomly
      matched with a twice-larger group of Hospital A reports from the same category (n
      = 304). Multivariate linear regression was used to analyze the association
      between the primary outcome (percentage of items described in dictated VCUG
      report) and the type of radiologist and institution. RESULTS: Of the 456 studies,
      66% were in girls, 56% were in those <12 months old, and the indication was
      urinary tract infection (UTI) in 81%. The mean percentage of items reported was
      67 +/- 14% (74 +/- 7% at free-standing pediatric hospitals, 61 +/- 10% at
      pediatric hospitals within a hospital, and 48 +/- 11% at non-pediatric
      facilities). In multivariate analysis, VCUG reports generated at non-pediatric
      facilities had 17% fewer items included (95% CI: 14.5-19.7%, P < 0.0001), and
      pediatric hospitals within a hospital had 9% fewer items included (5.9-12.5%, P <
      0.0001) when compared to free-standing pediatric hospitals. Reports read by a
      pediatric radiologist had 12% more items included (9.1-15.3%, P < 0.0001)
      compared to those read by a non-pediatric radiologist. CONCLUSION: More complete
      VCUG reports were observed when generated at free-standing pediatric hospitals
      and when interpreted by a pediatric radiologist.

PMID- 24859359
TI  - Postartesunate delayed hemolysis is a predictable event related to the lifesaving
      effect of artemisinins.
AB  - Patients with severe malaria treated with artesunate sometimes experience a
      delayed hemolytic episode. Artesunate (AS) induces pitting, a splenic process
      whereby dead parasites are expelled from their host erythrocytes. These once
      infected erythrocytes then return to the circulation. We analyzed hematologic
      parameters in 123 travelers treated with AS for severe malaria. Among 60
      nontransfused patients observed for more than 8 days, 13 (22%) had delayed
      hemolysis. The peak concentration of circulating once-infected erythrocytes was
      measured during the first week in 21 patients and was significantly higher in 9
      patients with delayed hemolysis than in 12 with other patterns of anemia (0.30 vs
      0.07; P = .0001). The threshold of 180 million once-infected erythrocytes per
      liter discriminated patients with delayed hemolysis with 89% sensitivity and 83%
      specificity. Once-infected erythrocyte morphology analyzed by using ImageStream
      in 4 patients showed an 8.9% reduction in their projected area, an alteration
      likely contributing to their shorter lifespan. Delayed clearance of infected
      erythrocytes spared by pitting during AS treatment is an original mechanism of
      hemolytic anemia. Our findings consolidate a disease framework for posttreatment
      anemia in malaria in which delayed hemolysis is a new entity. The early
      concentration of once-infected erythrocytes is a solid candidate marker to
      predict post-AS delayed hemolysis. 

PMID- 24859360
TI  - Thrombotic thrombocytopenic purpura and pregnancy: presentation, management, and
      subsequent pregnancy outcomes.
AB  - Pregnancy can precipitate thrombotic thrombocytopenic purpura (TTP). We present a
      prospective study of TTP cases from the United Kingdom Thrombotic
      Thrombocytopenic Purpura (UK TTP) Registry with clinical and laboratory data from
      the largest cohort of pregnancy-associated TTP and describe management through
      pregnancy, averting fetal loss and maternal complications. Thirty-five women
      presented with a first TTP episode during pregnancy: 23/47 with their first
      congenital TTP (cTTP) episode and 12/47 with acute acquired TTP in pregnancy. TTP
      presented primarily in the third trimester/postpartum, but fetal loss was highest
      in the second trimester. Fetal loss occurred in 16/38 pregnancies before cTTP was
      diagnosed, but in none of the 15 subsequent managed pregnancies. Seventeen of 23
      congenital cases had a missense mutation, C3178T, within exon 24 (R1060W). There
      were 8 novel mutations. In acquired TTP presentations, fetal loss occurred in
      5/18 pregnancies and 2 terminations because of disease. We also present data on
      12 women with a history of nonpregnancy-associated TTP: 18 subsequent pregnancies
      have been successfully managed, guided by ADAMTS13 levels. cTTP presents more
      frequently than acquired TTP during pregnancy and must be differentiated by
      ADAMTS13 analysis. Careful diagnosis, monitoring, and treatment in congenital and
      acquired TTP have assisted in excellent pregnancy outcomes. 

PMID- 24859358
TI  - Genetic susceptibility to type 2 diabetes and obesity: from genome-wide
      association studies to rare variants and beyond.
AB  - During the past 7 years, genome-wide association studies have shed light on the
      contribution of common genomic variants to the genetic architecture of type 2
      diabetes, obesity and related intermediate phenotypes. The discoveries have
      firmly established more than 175 genomic loci associated with these phenotypes.
      Despite the tight correlation between type 2 diabetes and obesity, these
      conditions do not appear to share a common genetic background, since they have
      few genetic risk loci in common. The recent genetic discoveries do however
      highlight specific details of the interplay between the pathogenesis of type 2
      diabetes, insulin resistance and obesity. The focus is currently shifting towards
      investigations of data from targeted array-based genotyping and exome and genome
      sequencing to study the individual and combined effect of low-frequency and rare
      variants in metabolic disease. Here we review recent progress as regards the
      concepts, methodologies and derived outcomes of studies of the genetics of type 2
      diabetes and obesity, and discuss avenues to be investigated in the future within
      this research field. 

PMID- 24859361
TI  - Real world data on primary treatment for mantle cell lymphoma: a Nordic Lymphoma
      Group observational study.
AB  - There is consensus that young patients with mantle cell lymphoma (MCL) should
      receive intensive immunochemotherapy regimens, but optimal treatment of elderly
      patients as well for as patients with limited or indolent disease is not defined.
      Our aim was to evaluate and compare outcome in relation to prognostic factors and
      first-line treatment in patients with MCL in a population-based data set. Data
      were collected from the Swedish and Danish Lymphoma Registries from the period of
      2000 to 2011. A total of 1389 patients were diagnosed with MCL. During this
      period, age-standardized incidence MCL increased, most prominently among males.
      Furthermore, male gender was associated with inferior overall survival (OS) in
      multivariate analysis (hazard ratio [HR] = 1.36; P = .002). Forty-three (3.6%)
      patients with stage I-II disease received radiotherapy with curative intent,
      showing a 3-year OS of 93%. Twenty-nine (2.4%) patients followed a watch-and-wait
      approach and showed a 3-year OS of 79.8%. Among patients receiving systemic
      treatment, rituximab (n = 766; HR = 0.66; P = .001) and autologous stem cell
      transplant (n = 273; HR = 0.55; P = .004) were independently associated with
      improved OS in multivariate analysis. Hence, by a population-based approach, we
      were able to provide novel data on prognostic factors and primary treatment of
      MCL, applicable to routine clinical practice. 

PMID- 24859362
TI  - Rates, management, and outcome of rivaroxaban bleeding in daily care: results
      from the Dresden NOAC registry.
AB  - Worldwide, rivaroxaban is increasingly used for stroke prevention in atrial
      fibrillation and treatment of venous thromboembolism, but little is known about
      rivaroxaban-related bleeding complications in daily care. Using data from a
      prospective, noninterventional oral anticoagulation registry of daily care
      patients (Dresden NOAC registry), we analyzed rates, management, and outcome of
      rivaroxaban-related bleeding. Between October 1, 2011, and December 31, 2013,
      1776 rivaroxaban patients were enrolled. So far, 762 patients (42.9%) reported
      1082 bleeding events during/within 3 days after last intake of rivaroxaban (58.9%
      minor, 35.0% of nonmajor clinically relevant, and 6.1% major bleeding according
      to International Society on Thrombosis and Haemostasis definition). In case of
      major bleeding, surgical or interventional treatment was needed in 37.8% and
      prothrombin complex concentrate in 9.1%. In the time-to-first-event analysis, 100
      patient-year rates of major bleeding were 3.1 (95% confidence interval 2.2-4.3)
      for stroke prevention in atrial fibrillation and 4.1 (95% confidence interval 2.5
      6.4) for venous thromboembolism patients, respectively. In the as-treated
      analysis, case fatality rates of bleeding leading to hospitalizations were 5.1%
      and 6.3% at days 30 and 90 after bleeding, respectively. Our data indicate that,
      in real life, rates of rivaroxaban-related major bleeding may be lower and that
      the outcome may at least not be worse than that of major vitamin K antagonist
      bleeding, and probably better. This trial was registered at
      www.clinicaltrials.gov as identifier #NCT01588119. 

PMID- 24859363
TI  - Carfilzomib, rituximab, and dexamethasone (CaRD) treatment offers a neuropathy
      sparing approach for treating Waldenstrom's macroglobulinemia.
AB  - Bortezomib frequently produces severe treatment-related peripheral neuropathy
      (PN) in Waldenstrom's macroglobulinemia (WM). Carfilzomib is a neuropathy-sparing
      proteasome inhibitor. We examined carfilzomib, rituximab, and dexamethasone
      (CaRD) in symptomatic WM patients naive to bortezomib and rituximab. Protocol
      therapy consisted of intravenous carfilzomib, 20 mg/m2 (cycle 1) and 36 mg/m(2)
      (cycles 2-6), with intravenous dexamethasone, 20 mg, on days 1, 2, 8, and 9, and
      rituximab, 375 mg/m(2), on days 2 and 9 every 21 days. Maintenance therapy
      followed 8 weeks later with intravenous carfilzomib, 36 mg/m(2), and intravenous
      dexamethasone, 20 mg, on days 1 and 2, and rituximab, 375 mg/m(2), on day 2 every
      8 weeks for 8 cycles. Overall response rate was 87.1% (1 complete response, 10
      very good partial responses, 10 partial responses, and 6 minimal responses) and
      was not impacted by MYD88(L265P) or CXCR4(WHIM) mutation status. With a median
      follow-up of 15.4 months, 20 patients remain progression free. Grade >=2
      toxicities included asymptomatic hyperlipasemia (41.9%), reversible neutropenia
      (12.9%), and cardiomyopathy in 1 patient (3.2%) with multiple risk factors, and
      PN in 1 patient (3.2%) which was grade 2. Declines in serum IgA and IgG were
      common. CaRD offers a neuropathy-sparing approach for proteasome inhibitor-based
      therapy in WM. This trial is registered at www.clinicaltrials.gov as
      #NCT01470196. 

PMID- 24859364
TI  - Prognosis for patients with CML and >10% BCR-ABL1 after 3 months of imatinib
      depends on the rate of BCR-ABL1 decline.
AB  - In chronic myeloid leukemia (CML) patients, a breakpoint cluster region-Abelson
      (BCR-ABL1) value >10% at 3 months of therapy is statistically associated with
      poorer outcome, yet many of these patients still achieve satisfactory outcomes.
      We investigated 528 first-line imatinib-treated patients to determine whether
      patients with the poorest outcome can be better discriminated at 3 months. All
      outcomes were significantly superior for the 410 patients with BCR-ABL1 <=10% at
      3 months (P < .001). However, the poorest outcomes among the 95 evaluable
      patients with BCR-ABL1 >10% at 3 months were identified by the rate of BCR-ABL1
      decline from baseline, assessed by estimating the number of days over which BCR
      ABL1 halved. Patients with BCR-ABL1 halving time <76 days (n = 74) had
      significantly superior outcomes compared with patients whose BCR-ABL1 values did
      not halve by 76 days (n = 21; 4-year overall survival, 95% vs 58%, P = .0002;
      progression-free survival, 92% vs 63%, P = .008; failure-free survival, 59% vs
      6%, P < .0001; and major molecular response, 54% vs 5%, P = .008). By
      multivariate analysis, the halving time was an independent predictor of outcome
      in this poor risk group. Our study highlighted that the rate of BCR-ABL1 decline
      may be a critical prognostic discriminator of the patients with very poor outcome
      among those >10% at 3 months. The International Randomized IFN vs STI571 (IRIS)
      trial was registered at http://www.clinicaltrials.gov as #NCT00006343. The
      Tyrosine Kinase Inhibitor Optimization and Selectivity (TOPS) trial was
      registered at http://www.clinicaltrials.gov as #NCT00124748. The Therapeutic
      Intensification in DE-novo Leukaemia (TIDEL) I trial was registered at
      http://www.ANZCTR.org.au as #ACTRN12607000614493. The TIDEL II trial was
      registered at http://www.ANZCTR.org.au as #ACTRN12607000325404. 

PMID- 24859365
TI  - Physiological functions of TNF family receptor/ligand interactions in
      hematopoiesis and transplantation.
AB  - Secretion of ligands of the tumor necrosis factor (TNF) superfamily is a
      conserved response of parenchymal tissues to injury and inflammation that
      commonly perpetuates elimination of dysfunctional cellular components by
      apoptosis. The same signals of tissue injury that induce apoptosis in somatic
      cells activate stem cells and initiate the process of tissue regeneration as a
      coupling mechanism of injury and recovery. Hematopoietic stem and progenitor
      cells upregulate the TNF family receptors under stress conditions and are
      transduced with trophic signals. The progeny gradually acquires sensitivity to
      receptor-mediated apoptosis along the differentiation process, which becomes the
      major mechanism of negative regulation of mature proliferating hematopoietic
      lineages and immune homeostasis. Receptor/ligand interactions of the TNF family
      are physiological mechanisms transducing the need for repair, which may be
      harnessed in pathological conditions and transplantation. Because these
      interactions are physiological mechanisms of injury, neutralization of these
      pathways has to be carefully considered in disorders that do not involve
      intrinsic aberrations of excessive susceptibility to apoptosis. 

PMID- 24859366
TI  - Activity of SL-401, a targeted therapy directed to interleukin-3 receptor, in
      blastic plasmacytoid dendritic cell neoplasm patients.
AB  - This is the first prospective study of treatment of patients with blastic
      plasmacytoid dendritic cell neoplasm (BPDCN), an aggressive hematologic
      malignancy derived from plasmacytoid dendritic cells that typically involves the
      skin and rapidly progresses to a leukemia phase. Despite being initially
      responsive to intensive combination chemotherapy, most patients relapse and
      succumb to their disease. Because BPDCN blasts overexpress the interleukin-3
      receptor (IL3R), the activity of SL-401, diptheria toxin (DT)388IL3 composed of
      the catalytic and translocation domains of DT fused to IL3, was evaluated in
      BPDCN patients in a phase 1-2 study. Eleven patients were treated with a single
      course of SL-401 at 12.5 MUg/kg intravenously over 15 minutes daily for up to 5
      doses; 3 patients who had initial responses to SL-401 received a second course in
      relapse. The most common adverse events including fever, chills, hypotension,
      edema, hypoalbuminemia, thrombocytopenia, and transaminasemia were transient.
      Seven of 9 evaluable (78%) BPDCN patients had major responses including 5
      complete responses and 2 partial responses after a single course of SL-401. The
      median duration of responses was 5 months (range, 1-20+ months). Further studies
      of SL-401 in BPDCN including those involving multiple sequential courses,
      alternate schedules, and combinations with other therapeutics are warranted. This
      trial is registered at clinicaltrials.gov as #NCT00397579. 

PMID- 24859367
TI  - Surgical fixation of displaced midshaft clavicle fractures: elastic
      intramedullary nailing versus precontoured plating.
AB  - BACKGROUND: This prospective comparative study was done to evaluate the
      effectiveness of implants of different design (titanium elastic intramedullary
      nail versus anatomical precontoured dynamic compression plate) in treatment of
      displaced midshaft clavicular fractures. MATERIALS AND METHODS: Sixty-six
      patients between 18 and 65 years of age were included in this study. They were
      randomized in two groups to be treated with either elastic intramedullary nail
      (EIN) or plate. Clinical and radiological assessments were performed at regular
      intervals. Outcomes and complications of both groups over 2 years of follow-up
      time were compared. RESULTS: Length of incision, operation time, blood loss and
      duration of hospital stay were significantly less for the EIN group. American
      Shoulder and Elbow Surgeons (ASES) and Constant Shoulder scores were
      significantly higher (p < 0.05) in the plating group than the EIN group for the
      first 2 months but there was no significant difference found between the two
      groups regarding functional and radiological outcome at the 2-year follow-up.
      Significantly higher rates of refracture after implant removal (p = 0.045) in the
      plating group was observed. Infection and revision surgery rates were also higher
      in the plate group, but this difference was insignificant (p > 0.05).
      CONCLUSIONS: EIN is a safe, minimally invasive surgical technique with a lower
      complication rate, faster return to daily activities, excellent cosmetic and
      comparable functional results, and can be used as an equally effective
      alternative to plate fixation in displaced midshaft clavicle fractures. LEVEL OF
      EVIDENCE: Level 2.

PMID- 24859368
TI  - In vitro and in vivo evaluation of silicated hydroxyapatite and impact of insulin
      adsorption.
AB  - This study evaluates the biological behaviour, in vitro and in vivo, of silicated
      hydroxyapatite with and without insulin adsorbed on the material surface. Insulin
      was successfully adsorbed on hydroxyapatite and silicated hydroxyapatite
      bioceramics. The modification of the protein secondary structure after the
      adsorption was investigated by means of infrared and circular dichroism
      spectroscopic methods. Both results were in agreement and indicated that the
      adsorption process was likely to change the secondary structure of the insulin
      from a majority of alpha-helix to a beta-sheet form. The biocompatibility of both
      materials, with and without adsorbed insulin on their surface, was demonstrated
      in vitro by indirect and direct assays. A good viability of the cells was found
      and no proliferation effect was observed regardless of the material composition
      and of the presence or absence of insulin. Dense granules of each material were
      implanted subcutaneously in mice for 1, 3 and 9 weeks. At 9 weeks of
      implantation, a higher inflammatory response was observed for silicated
      hydroxyapatite than for pure hydroxyapatite but no significant effect of adsorbed
      insulin was detected. Though the presence of silicon in hydroxyapatite did not
      improve the biological behaviour, the silicon substituted hydroxyapatite remained
      highly viable.

PMID- 24859370
TI  - Microsatellite-primed PCR for intra-species genetic relatedness in Trichophyton
      ajelloi strains isolated in poland from various soil samples.
AB  - Trichophyton ajelloi is a geophilic dermatophyte that specializes in the
      decomposition of native keratin. It exists in soil with a permanent influx of
      keratin matter. In the present study, two PCR-based methods were used for the
      identification and intra-species differentiation of T. ajelloi strains isolated
      from 3 types of soils with different physicochemical properties. The first
      method, employed for molecular identification, was PCR amplification of the 5.8S
      rRNA gene and its flanking regions encoding internal transcribed spacers (ITSs),
      followed by restriction enzyme digestion using endonuclease HinfI. The second
      method, employed for molecular differentiation, was microsatellite-primed PCR
      (MSP-PCR) using the repetitive oligonucleotide (GACA)4. All the T. ajelloi
      strains were also identified using a traditional culture method. Our results
      showed that molecular identification using the PCR-restriction fragment length
      polymorphism (PCR-RFLP) method agreed with the identification made using the
      traditional approach. On the other hand, PCR-RFLP results showed no strain
      differentiation, while MSP-PCR using the (GACA)4 primer identified different
      varieties among the T. ajelloi strains. The reasons for the intra-species
      differentiation of T. ajelloi have been discussed. 

PMID- 24859371
TI  - Regional variation in medication-taking behaviour of new users of oral anti
      hyperglycaemic therapy in Ireland.
AB  - BACKGROUND: Few studies have investigated regional variation in medication-taking
      behaviour. The purpose of this study was to investigate whether there are
      regional differences in non-persistence and non-adherence to oral anti
      hyperglycaemic agents in patients initiating therapy and examine if any
      association exists between different types of comorbidity in terms of medication
      taking behaviour. METHODS: The Irish Health Services Executive (HSE) pharmacy
      claims database was used to identify new users of metformin or sulphonylureas,
      aged >=25 years, initiating therapy between June 2009 and December 2010. Non
      persistence and non-adherence were examined up to 12 months post-initiation.
      Comorbidity was assessed using modified RxRisk and RxRisk-V indices, and
      classified as either concordant and/or discordant with diabetes. Adjusted hazard
      ratios (HRs) and 95% confidence intervals (95% CIs) for non-persistence were
      determined in relation to both HSE region and comorbidity type using Cox
      proportional hazards model, adjusting for age, sex and initial OAH prescribed.
      Logistic regression analysis, adjusting for these covariates, was used to
      determine the adjusted odds ratios (ORs) and 95% CIs for non-adherence for both
      HSE region and comorbidity type. RESULTS: Results showed little overall
      difference between regions. The largest reduction for both non-persistence (HR
      0.86, 95% CI 0.80, 0.94) and non-adherence (OR 0.83, 95% CI 0.74, 0.93) was
      observed in the south. Any comorbidity was associated with a reduced risk of non
      persistence and non-adherence. CONCLUSIONS: Interventions to optimise medication
      taking in patients with T2DM should be implemented nationally to improve the
      overall level of adherence and persistence, especially in patients with no
      comorbidity.

PMID- 24859372
TI  - An audit of drug shortages in a community pharmacy practice.
AB  - BACKGROUND: There are no firm data on drug shortages in Irish community pharmacy.
      This prospective observational study aimed to characterise the drug shortage
      problem in an Irish community pharmacy. AIMS: The primary aim was to determine
      numbers and durations of drug shortages. Secondary aims included comparing these
      shortages with Irish Pharmacy Union (IPU) drug shortage lists and determining the
      frequency with which notifications were received prior to shortages. Further
      secondary aims were to examine relationships between causes of drug shortages and
      drug costs and between causes of drug shortages and shortage durations. METHODS:
      The study took place in a community pharmacy in a Limerick City suburb between
      October 2012 and February 2013. Data were collected daily regarding drugs that
      were dispensed, but unavailable to purchase. Suppliers/manufacturers provided
      data on the reasons for shortages. RESULTS: 65/1,232 dispensed drugs (5.3%) were
      in short supply over the study period. Median shortage duration was 13 days
      (interquartile range 4-32 days) and median cost was <euro>8.10. Numbers of
      unavailable drugs by month varied from 13 to 38. Monthly IPU drug shortage lists
      identified between six and eight of these shortages depending on the month. Two
      notifications were received from suppliers/manufacturers regarding shortages.
      Parallel exports had the highest mean costs (mean <euro>38.05) and manufacturing
      problems were associated with the longest durations (mean 57.44 days).
      CONCLUSIONS: This study highlights the drug shortage problem in an Irish
      community pharmacy. We propose that enhanced communication between all
      stakeholders is the most worthwhile solution. Further studies are needed.

PMID- 24859375
TI  - Hypercohones D-G, New Polycyclic Polyprenylated Acylphloroglucinol Type Natural
      Products from Hypericum cohaerens.
AB  - ABSTRACT: Four new polycyclic polyprenylated acylphloroglucinol type metabolites,
      hypercohones D-G (1-4), along with four known analogues (5-8), were isolated from
      the aerial parts of Hypericum cohaerens. The structures of these isolates were
      elucidated by extensive spectroscopic methods. The inhibitory activities of these
      isolates against five human cancer cell lines in vitro were also tested.

PMID- 24859374
TI  - Effects of exercise training on circulating and skeletal muscle renin-angiotensin
      system in chronic heart failure rats.
AB  - BACKGROUND: Accumulated evidence shows that the ACE-AngII-AT1 axis of the renin
      angiotensin system (RAS) is markedly activated in chronic heart failure (CHF).
      Recent studies provide information that Angiotensin (Ang)-(1-7), a metabolite of
      AngII, counteracts the effects of AngII. However, this balance between AngII and
      Ang-(1-7) is still little understood in CHF. We investigated the effects of
      exercise training on circulating and skeletal muscle RAS in the ischemic model of
      CHF. METHODS/MAIN RESULTS: Male Wistar rats underwent left coronary artery
      ligation or a Sham operation. They were divided into four groups: 1) Sedentary
      Sham (Sham-S), 2) exercise-trained Sham (Sham-Ex), sedentary CHF (CHF-S), and
      exercise-trained CHF (CHF-Ex). Angiotensin concentrations and ACE and ACE2
      activity in the circulation and skeletal muscle (soleus and plantaris) were
      quantified. Skeletal muscle ACE and ACE2 protein expression, and AT1, AT2, and
      Mas receptor gene expression were also evaluated. CHF reduced ACE2 serum
      activity. Exercise training restored ACE2 and reduced ACE activity in CHF.
      Exercise training reduced plasma AngII concentration in both Sham and CHF rats
      and increased the Ang-(1-7)/AngII ratio in CHF rats. CHF and exercise training
      did not change skeletal muscle ACE and ACE2 activity and protein expression. CHF
      increased AngII levels in both soleus and plantaris muscle, and exercise training
      normalized them. Exercise training increased Ang-(1-7) in the plantaris muscle of
      CHF rats. The AT1 receptor was only increased in the soleus muscle of CHF rats,
      and exercise training normalized it. Exercise training increased the expression
      of the Mas receptor in the soleus muscle of both exercise-trained groups, and
      normalized it in plantaris muscle. CONCLUSIONS: Exercise training causes a shift
      in RAS towards the Ang-(1-7)-Mas axis in skeletal muscle, which can be influenced
      by skeletal muscle metabolic characteristics. The changes in RAS circulation do
      not necessarily reflect the changes occurring in the RAS of skeletal muscle.

PMID- 24859373
TI  - Neighborhood characteristics and leukocyte telomere length: the Multi-Ethnic
      Study of Atherosclerosis.
AB  - Telomeres are the protective caps at the ends of eukaryotic chromosomes.
      Telomeres get shorter each time a cell divides, and critically shortened
      telomeres trigger cellular senescence. Thus, telomere length is hypothesized to
      be a biological marker of aging. The purpose of this study was to examine the
      association between neighborhood characteristics and leukocyte telomere length.
      Using data from a subsample (n=978) of the Multi-Ethnic Study of Atherosclerosis,
      a population-based study of women and men aged 45-84, we found that neighborhood
      social environment (but not neighborhood socioeconomic disadvantage) was
      associated with telomere length. Respondents who lived in neighborhoods
      characterized by lower aesthetic quality, safety, and social cohesion had shorter
      telomeres than those who lived in neighborhoods with a more salutary social
      environment, even after adjusting for individual-level socioeconomic status and
      biomedical and lifestyle factors related to telomere length. Telomere length may
      be one biological mechanism by which neighborhood characteristics influence an
      individual's risk of disease and death. 

PMID- 24859378
TI  - Impact of specific KRAS mutation in exon 2 on clinical outcome of chemotherapy-
      and radiotherapy-treated colorectal adenocarcinoma patients.
AB  - BACKGROUND AND OBJECTIVES: Knowledge obtained via high-throughput technologies,
      used for tumor genome sequencing or identifying gene expression and methylation
      signatures, is clinically applicable thanks to molecular characterization in the
      context of tumor development and progression. This study was conducted to assess
      the impact of specific KRAS mutation in codons 12 and 13 on clinical outcome of
      chemotherapy and radiotherapy in colorectal cancer patients. METHODS: A total of
      239 samples of colorectal adenocarcinoma underwent histological evaluation and
      DNA isolation. RESULTS AND CONCLUSIONS: Patients with a mutation in KRAS codon 13
      experienced worse outcome than those with a mutation in KRAS codon 12. Moreover,
      the cases of mutations in KRAS codons 12 or 13 were associated with a
      significantly higher mortality than the cases of wild-type KRAS, and some
      patients with KRAS mutated in codon 12 had an exceptionally long overall
      survival. Finally, primary preoperative radiation therapy followed by surgery
      significantly increased overall survival more efficiently than surgery followed
      by chemotherapy. This should be investigated in further studies. The fact that
      all patients treated with radiotherapy + surgery were alive, again focused our
      attention on the effect of preoperative radiation therapy on the prognosis for
      colorectal cancer patients. However, the number of patients in this subgroup is
      too small to allow any specific explanation for this observation. We should,
      rather, point out a problem for further investigation.

PMID- 24859377
TI  - Myoglobin functions in the heart.
AB  - The physiological role of myoglobin (Mb) within the heart depends on its
      oxygenation state. The myocardium exhibits a broad oxygen partial pressure (pO2)
      spectrum with a transmural gradient from the epicardial to the subendocardial
      layer, ranging from arterial values to an average of 19.3 mm Hg down to 0 mm Hg.
      The function of Mb as an O2 storage depot is well appreciated, especially during
      systolic compression. In addition, Mb controls myocardial nitric oxide (NO)
      homeostasis and thus modulates mitochondrial respiration under physiological and
      pathological conditions. We recently discovered the role of Mb as a myocardial O2
      sensor; in its oxygenated state Mb scavenges NO, protecting the heart from the
      deleterious effects of excessive NO. Under hypoxia, however, deoxygenated Mb
      changes its role from an NO scavenger to an NO producer. The NO produced protects
      the cell from short phases of hypoxia and from myocardial ischemia/reperfusion
      injury. In this review we summarize the traditional and novel aspects of Mb and
      its (patho)physiological role in the heart.

PMID- 24859379
TI  - Interactions of anticancer drugs with biomembranes: what can we learn from model
      membranes?
AB  - The interactions of anticancer drugs with cell membranes are of primary
      importance for drug transport, accumulation and activity. However, these
      interactions are very difficult to investigate because of the complexity of
      biological membranes. Lipid model membranes have therefore been built to gain
      insight into the collective role of lipids in drug-membrane interactions.
      Membranes can act as a barrier for drug molecules, sequester them or conversely
      may allow them to freely diffuse, thereby modulating the accumulation of drugs
      into cells. Lipid membranes also affect the ability of the efflux pump Pgp to
      bind and efflux anticancer drugs from cells. On the other hand, anticancer drugs
      can alter the structure and properties of lipid membranes, which are expected to
      influence the functioning of embedded proteins. The relevance of lipid model
      membranes to assess interactions between anticancer drugs and biomembranes is
      evidenced. 

PMID- 24859380
TI  - Bleaching effect of activation of hydrogen peroxide using photon-initiated
      photoacoustic streaming technique.
AB  - OBJECTIVES: This study aims to investigate the bleaching effectiveness of photon
      initiated photoacoustic streaming (PIPS) using 35 % hydrogen peroxide on
      discolored teeth as compared with different devital bleaching techniques.
      MATERIALS AND METHODS: Fifty extracted human mandibular incisors were collected
      and artificially stained using sheep's blood. The teeth were then randomly
      divided into five groups according to the different bleaching procedures to be
      tested: walking bleach with sodium perborate and with 35 % hydrogen peroxide gel,
      both for 1 week; PIPS using 35 % hydrogen peroxide liquid for 30 min; and just 35
      % hydrogen peroxide, as a liquid and as a gel (again, for 30 min).
      Spectrophotometric measurements were obtained on the buccal surfaces of the
      crowns, at the beginning, just after the bleaching procedures had been performed,
      and the following first, third, and seventh days. The ?E values were calculated,
      and the data were analyzed with a two-way analysis of variance (P = 0.05).
      RESULTS: There were statistically significant differences between the PIPS
      technique using 35 % hydrogen peroxide liquid and the 35 % hydrogen peroxide
      liquid and gel without PIPS immediately after the procedures (P < 0.05). On Days
      1, 3, and 7, the PIPS technique further bleached specimens more than all of the
      other techniques (P < 0.05). CONCLUSIONS: The PIPS technique using 35 % hydrogen
      peroxide was found to be more effective than all of the conventional techniques.
      CLINICAL RELEVANCE: Within limitations of this study, PIPS technique using
      hydrogen peroxide was superior to the conventional techniques. Further studies
      should be conducted to determine if the PIPS technique results in any
      complications, particularly cervical resorption.

PMID- 24859381
TI  - Effect of different curing protocols on the mechanical properties of low
      viscosity bulk-fill composites.
AB  - OBJECTIVES: This study aimed to assess the impact of curing conditions-exposure
      time, mode, energy density and exposure distance-on the efficiency of curing
      flowable bulk-fill resin-based composites (RBCs) at simulated clinical relevant
      filling depths. MATERIALS AND METHODS: Four flowable bulk-fill RBCs were
      investigated by assessing in 200 MUm steps the variation in micro-mechanical
      properties (Vickers hardness (HV) and indentation modulus (E)) within simulated 6
      mm-deep fillings (n = 5), considering 16 different curing modes/conditions. The
      exposure duration was 5, 20 and 40 s in the standard power mode; 3, 4 and 8 s in
      the high power mode; and 3 and 6 s in the plasma mode. Besides, the curing unit
      was placed at 0 and 7 mm distance away from the specimen's surface. Measurements
      were performed after 24 h of storage in distilled water at 37  degrees C. The
      depth of cure (DOC) was calculated as the 80 % hardness drop-off. The curing
      unit's irradiance at exposure distances up to 10 mm was monitored for all
      irradiation modes in 1 mm steps by means of a laboratory-grade spectrometer.
      RESULTS: Results were compared using one- and multiple way ANOVA and Tukey's
      honest significant difference (HSD) post hoc test (alpha = 0.05). A multivariate
      analysis (general linear model) assessed the effect strength of the parameters
      material, energy density reaching the specimen's surface (2.63 to 47.03 J/cm(2)),
      exposure distance and curing mode on HV, E and DOC. The effect of the parameter
      material was significant and strong on all measured properties (p < 0.05, partial
      eta-squared (eta P (2)) = 0.683 for E, 0.724 for HV and 0.199 for DOC). Energy
      density exerted in all materials the strongest influence on the measured
      properties, while the influence of distance was strong on DOC and low or even not
      significant on HV and E. CONCLUSIONS: The susceptibility to variation in
      irradiance under the simulated clinical conditions was material dependent, while
      lower and upper energy density limits for curing the materials were defined.
      CLINICAL RELEVANCE: Materials react differently to the supplied irradiance. An
      exposure time of 20 s at moderate irradiance is recommended for all materials.
      The highest mechanical properties were reached not at the specimens' surface, but
      in deeper layers (0.4 to 3.1 mm).

PMID- 24859382
TI  - Differentiating neurons derived from human umbilical cord blood stem cells work
      as a test system for developmental neurotoxicity.
AB  - Differentiating neuronal cells derived from human umbilical cord blood stem cells
      have been used as an in vitro tool for the assessment of developmental
      neurotoxicity of monocrotophos (MCP), an organophosphate pesticide. The
      differentiating cells were exposed to MCP during the different stages of
      maturation, viz., days 2, 4, and 8, and changes in the makers of cell
      proliferation, neuronal differentiation, neuronal injuries, and receptors were
      studied. We found significant upregulation in the different MAPKs, apoptosis, and
      neurogenesis markers and downregulation in the cell proliferation markers during
      neuronal differentiation. We further identified significant upregulation in the
      expression of different MAPKs and proteins involved in oxidative stress,
      apoptosis, and calpain pathways in the mid-differentiating cells exposed to MCP.
      The upregulated levels of these proteins seem to be the main cause of alteration
      during the differentiation process towards apoptosis as a fine-tune of pro
      apoptotic and anti-apoptotic proteins are desirable for the process of
      differentiation without apoptosis. The decreased acetylcholinesterase activity,
      dopaminergic, and cholinergic receptors and increased acetylcholine levels in the
      differentiating neuronal cells indicate the vulnerability of these cells towards
      MCP-induced neurotoxicity. Our data confirms that differentiating neuronal cells
      derived from human umbilical cord stem cells could be used as a powerful tool to
      assess the developmental neurotoxicity in human beings.

PMID- 24859383
TI  - Induction of GDNF and BDNF by hRheb(S16H) transduction of SNpc neurons:
      neuroprotective mechanisms of hRheb(S16H) in a model of Parkinson's disease.
AB  - The transduction of dopaminergic (DA) neurons with human ras homolog enriched in
      brain, which has a S16H mutation [hRheb(S16H)] protects the nigrostriatal DA
      projection in the 6-hydroxydopamine (6-OHDA)-treated animal model of Parkinson's
      disease (PD). However, it is still unclear whether the expression of active hRheb
      induces the production of neurotrophic factors such as glial cell line-derived
      neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF), which
      are involved in neuroprotection, in mature neurons. Here, we show that
      transduction of nigral DA neurons with hRheb(S16H) significantly increases the
      levels of phospho-cyclic adenosine monophosphate (cAMP) response element-binding
      protein (p-CREB), GDNF, and BDNF in neurons, which are attenuated by rapamycin, a
      specific inhibitor of mammalian target of rapamycin complex 1 (mTORC1). Moreover,
      treatment with specific neutralizing antibodies for GDNF and BDNF reduced the
      protective effects of hRheb(S16H) against 1-methyl-4-phenylpyridinium (MPP(+))
      induced neurotoxicity. These results show that activation of hRheb/mTORC1
      signaling pathway could impart to DA neurons the important ability to
      continuously produce GDNF and BDNF as therapeutic agents against PD.

PMID- 24859384
TI  - Vitamin A deficiency impairs spatial learning and memory: the mechanism of
      abnormal CBP-dependent histone acetylation regulated by retinoic acid receptor
      alpha.
AB  - Vitamin A (VA) is an essential micronutrient. Numerous studies have confirmed
      that VA deficiency (VAD) leads to a decline in learning and memory function. Our
      previous studies have demonstrated that retinoic acid nuclear receptor alpha
      (RARalpha) in the hippocampus plays a crucial role in learning and memory, but
      the exact mechanism for this process is unclear. Epigenetic modifications,
      particularly histone acetylation, are involved in nervous system development,
      learning and memory function, and the pathogenesis of neurodegenerative diseases.
      Histone acetyltransferases (HATs), such as CREB-binding protein (CBP), E1A
      binding protein p300 (p300), and p300/CBP-associated factor (PCAF), are critical
      for regulating memory function. The current study uses RARalpha and CBP as
      examples to study the connections between the RA signaling pathway and histone
      acetylation modification and to reveal the epigenetic mechanism in VAD-induced
      learning and memory impairment. This study examined the expression of RARalpha,
      HATs, acetylated histone H3/H4, and memory-related genes (Zif268, cFos, FosB), as
      well as the interaction of RARalpha and CBP in the hippocampus of 8-week-old
      rats. Additionally, the changes shown in vivo were further assessed in primary
      cultured neurons with the inhibition or overexpression of RARalpha. We found
      significantly lower levels of histone acetylation in the VAD rats. Furthermore,
      this downregulation, which impairs learning and memory, is induced by the
      dysregulation of CBP-dependent histone acetylation that is mediated by RARalpha.
      This work provides a solid theoretical foundation and experimental basis for the
      importance of ensuring sufficient nutritional VA during pregnancy and early life
      to prevent impairments of learning and memory in adulthood.

PMID- 24859385
TI  - Cystoid macular edema after pars plana vitrectomy for idiopathic epiretinal
      membrane.
AB  - BACKGROUND: To evaluate the incidence of cystoid macular edema (CME) after 23
      gauge pars plana vitrectomy (PPV) with or without combined cataract surgery for
      the treatment of idiopathic epiretinal membrane (ERM). METHODS: Retrospective,
      non-comparative, interventional case series. Data included patient age,
      indication for surgery, and intra- and post-operative complications. The follow
      up lasted 1 year. Best-corrected visual acuity (BCVA logMAR), central foveal
      thickness (CFT micron-MU) and the incidence of intra-retinal cysts were
      evaluated. CME was defined as post-operative observation of intra-retinal cysts
      at optical coherence tomography, preventing improvement or causing reduction of
      BCVA when compared to the pre-operative value. Statistical analysis was performed
      to identify the risk factors of CME. RESULTS: Two hundred and forty two eyes of
      242 patients underwent PPV for the treatment of idiopathic ERM. Statistical
      analysis showed that the presence of preoperative intra-retinal cysts were
      associated with persistent CME following surgery (odds ratio 3.89; 95%CI: 1.63
      9.28, P = 0.0004). However, postoperative CME occurred in 10 % of eyes that did
      not show preoperative CME. In addition, there was a significant correlation
      between the baseline value of CFT and the values of CFT at each time point during
      the follow up (p < 0.0001), with greater values of the pre-operative thickness
      correlating to greater values of post-operative thickness. CONCLUSIONS:
      Persistent or new CME following surgery for idiopathic ERM are frequently
      identified after PPV for ERM. The statistical results of the current study
      suggest that intraretinal cysts and increased preoperative CFT are associated
      with reduced visual acuity after surgery.

PMID- 24859386
TI  - Upregulation of hypoxia-inducible factors and autophagy in von Hippel-Lindau
      associated retinal hemangioblastoma.
AB  - PURPOSE: To describe pathological and molecular changes of three patients with
      clinically severe von Hippel-Lindau (VHL)-associated retinal hemangioblastoma
      (RH) with rapid progression. METHODS: Medical records, ocular histopathology, and
      transmission electron microscopy from three cases of VHL-associated RHs at the
      National Eye Institute were retrospectively reviewed. One eye of each patient was
      enucleated. Hypoxia-inducible factor (HIF) 1alpha and HIF2alpha expressions were
      identified by quantitative reverse transcription polymerase chain reaction (qRT
      PCR) and immunohistochemistry. RESULTS: All three cases had rapidly growing RHs
      that were resistant to multiple conventional therapies and two (patients 1 and 2)
      were also resistant to multiple intravitreal anti-vascular endothelial growth
      factor (VEGF) treatments. Macroscopically, all the enucleated eyes had multiple
      RHs, serous retinal detachment, severe retinal disorganization and focal
      hemorrhages. Histopathology showed typical RHs composed of vacuolated foamy VHL
      cells and capillary networks. Retinal gliosis and hemorrhages were also
      presented. Additionally, T lymphocytes and macrophages infiltrated in the tumors
      of two patients resistant to anti-VEGF therapy. Immunohistochemistry, and qRT-PCR
      found upregulation of HIF1alpha in the retinal lesions of all eyes. Importantly,
      upregulation of HIF2alpha was exclusively detected in the two cases with
      inflammatory infiltration and resistance to anti-VEGF therapy. Ultrastructural
      images showed autophagy, lipid droplets, glycogen aggregations, and cytoplasmic
      degeneration in many VHL cells. CONCLUSIONS: Based on the histopathological and
      molecular pathological findings, autophagy, inflammation, and/or upregulation of
      HIF2alpha could potentially contribute to the aggressive course of RHs, resulting
      in the resistance to multiple anti-VEGF and radiation therapies in these
      patients.

PMID- 24859388
TI  - Antibiotic therapy versus no antibiotic therapy for children aged two to 59
      months with WHO-defined non-severe pneumonia and wheeze.
AB  - BACKGROUND: Worldwide, pneumonia is the leading cause of death among children
      under five years of age and accounts for approximately two million deaths
      annually. The World Health Organization (WHO) has developed case management
      guidelines based on simple clinical signs to help clinicians decide on the
      appropriate pneumonia treatment. Children and infants who exhibit fast breathing
      (50 breaths per minute or more in infants two months to 12 months of age and 40
      or more in children 12 months to five years of age) and cough are presumed to
      have non-severe pneumonia and the WHO recommends antibiotics. Implementation of
      these guidelines to identify and manage pneumonia at the community level has been
      shown to reduce acute respiratory infection (ARI)-related mortality by 36%,
      although apprehension exists regarding these results due to the questionable
      quality of evidence. As WHO guidelines do not make a distinction between viral
      and bacterial pneumonia, these children continue to receive antibiotics because
      of the concern that it may not be safe to do otherwise. Therefore, it is
      essential to explore the role of antibiotics in children with WHO-defined non
      severe pneumonia and wheeze and to develop effective guidelines for initial
      antibiotic treatment. OBJECTIVES: To evaluate the efficacy of antibiotic therapy
      versus no antibiotic therapy for children aged two to 59 months with WHO-defined
      non-severe pneumonia and wheeze. SEARCH METHODS: We searched CENTRAL (2014, Issue
      1), MEDLINE (1946 to March week 3, 2014), EMBASE (January 2010 to March 2014),
      CINAHL (1981 to March 2014), LILACS (1982 to March 2014), Networked Digital
      Library of Theses and Dissertations (23 July 2013) and Web of Science (1985 to
      March 2014). SELECTION CRITERIA: Randomised controlled trials (RCTs) evaluating
      the efficacy of antibiotic therapy versus no antibiotic therapy for children aged
      two to 59 months with non-severe pneumonia and wheeze. We considered studies that
      defined non-severe pneumonia as cough or difficulty in breathing with a
      respiratory rate above the WHO-defined age-specific values (respiratory rate of
      50 breaths per minute or more for children aged two to 12 months, or a
      respiratory rate of 40 breaths per minute or more for children aged 12 to 59
      months) and wheeze for inclusion. We have excluded non-RCTs (quasi-RCTs). DATA
      COLLECTION AND ANALYSIS: Two review authors independently assessed the search
      results and extracted data. MAIN RESULTS: We did not identify any study that
      completely fulfilled our inclusion criteria. AUTHORS' CONCLUSIONS: There is a
      clear need for RCTs to address this question in representative populations. We do
      not currently have evidence to support or challenge the continued use of
      antibiotics for the treatment of non-severe pneumonia, as suggested by WHO
      guidelines.

PMID- 24859387
TI  - Obstructive sleep apnea-hypopnea syndrome (OSAHS) and glaucomatous optic
      neuropathy.
AB  - Obstructive sleep apnea-hypopnea syndrome (OSAHS) is becoming widely accepted as
      a risk factor for glaucoma. We discuss the proposed mechanism involved in the
      pathogenesis of glaucoma in OSAHS, and review the published data on the
      association between these two conditions, as well as papers regarding functional
      and structural tests related with glaucomatous damage. There is increasing
      evidence that the prevalence of glaucoma is higher in OSAHS patients, especially
      in those with severe disease with apnea-hypopnea index (AHI) >30, and also that
      sleep disorders may be more frequent in patients with glaucoma, especially in
      those with normal tension glaucoma (NTG). Several ophthalmic signs and symptoms
      have been associated with this condition. Raised intraocular pressure (IOP),
      possibly related to increased body mass index, thinning of retinal nerve fiber
      layer (RNFL), and alteration of visual field (VF) indices has been demonstrated
      in many studies, in patients with no history of glaucoma or evidence of
      glaucomatous changes in the ophthalmic examination. A correlation of AHI with
      RNFL and VF indices has been described in some studies. Finally, corneal
      thinning, suspicious glaucomatous disc changes and anomalies in
      electrophysiological tests such as multifocal visual evoked potential have been
      described in patients with OSAHS, even in patients with normal findings in the
      optic nerve and VF, suggesting subclinical optic nerve involvement not detectable
      in conventional ophthalmic examinations. The pathogenesis of optic nerve
      involvement has been related to vascular and mechanical factors. Vascular factors
      include recurrent hypoxia with increased vascular resistance, autonomic
      deregulation, oxidative stress and inflammation linked to hypoxia and subsequent
      reperfusion, decreased cerebral perfusion pressure and direct hypoxic damage to
      the optic nerve. Proposed mechanical factors include increased IOP at night
      related to supine position and obesity, raised intracranial pressure and elastic
      fiber depletion in the lamina cribosa and/or trabeculum. In conclusion,
      ophthalmic evaluation should be recommended in patients with severe OSAHS, and
      the presence of sleep disorders should be investigated in patients with glaucoma,
      especially in NTG patients and in those with progressive damage despite
      controlled IOP, as treatment with continuous positive airway pressure may
      contribute to stabilizing the progression of glaucomatous damage. 

PMID- 24859389
TI  - Carboxymethylcellulose-tetrahydrocurcumin conjugates for colon-specific delivery
      of a novel anti-cancer agent, 4-amino tetrahydrocurcumin.
AB  - Several curcumin derivatives are now becoming increasingly of interest because of
      their bioactive attributes, especially their action as antioxidants and anti
      carcinogenic activities. Tetrahydrocurcumin (THC), an active metabolite of
      curcumin, was selected to be a proper starting material for the work presented
      here as it is stable in physiological pH and has the typical pharmacological
      properties of curcumin. We have now reported that novel synthesized water-soluble
      polymeric macromolecule prodrugs can specifically deliver the drug to the colon.
      To study the drug loading and drug release, THC was conjugated with a hydrophilic
      polymer, carboxymethylcellulose (CMC) with the degree of substitution (DS) values
      of 0.7 and 1.2. THC was also attached to two different spacers including p
      aminobenzoic acid (PABA) and p-aminohippuric acid (PAH) via an azo bond that was
      cleaved by the azoreductase activities of colonic bacteria. The novel active
      molecule, 4-amino-THC, was readily released from the conjugates in the colon
      (>62% within 24h) with only very small amounts released in the upper GI tract
      (<12% over 12h). The polymer conjugates showed chemical stability at various pH
      values along the gastrointestinal tract and increased water solubility of up to
      5mg/mL. 4-Amino-THC demonstrated cytotoxic ability against the human colon
      adenocarcinoma cell lines (HT-29) with an IC50 of 28.67 +/- 1.01 MUg/mL, and even
      greater selectivity (~ 4 folds) to inhibit HT-29 cells than to normal human colon
      epithelial cell lines while curcumin was a non-selective agent against both cell
      lines. Our study has demonstrated that the use of THC-CMC conjugates may be a
      promising colon-specific drug delivery system with its sustained release in the
      colon to be an effective treatment for colonic cancer.

PMID- 24859390
TI  - Storage stability of keratinocyte growth factor-2 in lyophilized formulations:
      effects of formulation physical properties and protein fraction at the solid-air
      interface.
AB  - Lyophilized formulations of keratinocyte growth factor-2 (KGF-2) were prepared
      with a range of disaccharide (sucrose or trehalose) and hydroxyethyl starch (HES)
      mass ratios. Protein degradation was assessed as a function of time of storage of
      the dried formulations at 40, 50 and 60 degrees C. Lyophilized and stored samples
      were rehydrated, and protein degradation was quantified by measuring loss of
      monomeric protein with size exclusion chromatography and by determining chemical
      degradation in the soluble fraction with reverse-phase chromatography. The
      secondary structure of the protein in the lyophilized formulations was studied
      with infrared spectroscopy. The magnitudes of degradation were compared the key
      physical properties of the formulations including retention of protein native
      secondary structure, glass transition temperature (Tg), inverse mean square
      displacements <u(2)>(-1) for hydrogen atoms (fast beta relaxation), and the
      relaxation time tau(beta), which correlates with relaxation due to fast Johari
      Goldstein motions in the glass (Xu et al., 2013) [1]. In addition, specific
      surface areas of the lyophilized formulations were determined by Brunauer-Emmet
      Teller analysis of krypton adsorption isotherms and used to estimate the fraction
      of the KGF-2 molecules residing at the solid-air interface. KGF-2 degradation
      rates were highest in formulations wherein the protein's structure was most
      perturbed, and wherein beta relaxations were fastest, but the dominant factor
      governing KGF-2 degradation in freeze-dried formulations was the fraction of the
      protein found at the glass solid-air interface. 

PMID- 24859391
TI  - Nanosuspension for the delivery of a poorly soluble anti-cancer kinase inhibitor.
AB  - We hypothesized that nanosuspensions could be promising for the delivery of the
      poorly water soluble anti-cancer multi-targeted kinase inhibitor, MTKi-327.
      Hence, the aims of this work were (i) to evaluate the MTKi-327 nanosuspension for
      parenteral and oral administrations and (ii) to compare this nanosuspension with
      other nanocarriers in terms of anti-cancer efficacy and pharmacokinetics.
      Therefore, four formulations of MTKi-327 were studied: (i) PEGylated PLGA-based
      nanoparticles, (ii) self-assembling PEG750-p-(CL-co-TMC) polymeric micelles,
      (iii) nanosuspensions of MTKi-327; and (iv) Captisol solution (pH=3.5). All the
      nano-formulations presented a size below 200 nm. Injections of the highest
      possible dose of the three nano-formulations did not induce any side effects in
      mice. In contrast, the maximum tolerated dose of the control Captisol solution
      was 20-fold lower than its highest possible dose. The highest regrowth delay of A
      431-tumor-bearing nude mice was obtained with MTKi-327 nanosuspension,
      administered intravenously, at a dose of 650 mg/kg. After intravenous and oral
      administration, the AUC0-infinity of MTKi-327 nanosuspension was 2.4-fold greater
      than that of the Captisol solution. Nanosuspension may be considered as an
      effective anti-cancer MTKi-327 delivery method due to (i) the higher MTKi-327
      maximum tolerated dose, (ii) the possible intravenous injection of MTKi-327,
      (iii) its ability to enhance the administered dose and (iv) its higher efficacy.

PMID- 24859393
TI  - Association of celiac disease and portal hypertension: Cirrhotic or noncirrhotic.

PMID- 24859392
TI  - Clinical and histopathological correlation of duodenal biopsy with IgA anti
      tissue transglutaminase titers in children with celiac disease.
AB  - BACKGROUND: Data correlating anti-tissue transglutaminase (tTG) antibody titers
      with severity of duodenal involvement is limited. OBJECTIVE: The aim of this
      study was to correlate IgA anti-tTG antibody titers with symptoms, anthropometric
      parameters, and duodenal histopathology. METHODS: Consecutively diagnosed
      patients of celiac disease as per modified ESPGHAN criteria presenting over a
      year were enrolled. Demographic data, symptoms, weight-for-age z score (WAZ),
      height-for-age z score (HAZ), IgA anti-tTG titer, and duodenal histopathology
      graded as per modified Marsh criteria were recorded. Spearman rank correlation
      test was used for association between TTG age, WAZ, and HAZ. Receiver operating
      curve (ROC), sensitivity, specificity, negative predictive value, and positive
      predictive value were used to obtain anti-tTG cutoff value predictive of Marsh
      grade 3. RESULTS: One hundred and forty-two patients with celiac disease were
      evaluated. tTG showed significant correlation with WAZ (r = 0.822, p = <0.001)
      and HAZ (r = 0.722, p = <0.001) but not with age (r = 0.202, p = 0.066). The
      median anti-tTG titers rose progressively with higher Marsh grade on
      histopathology (p = 0.001). The median anti-tTG titer was also significantly
      higher in patients with classic celiac disease as compared to non-diarrheal
      celiac disease (144 u/mL vs. 27, p = 0.02). Anti-tTG titer of 62.5 u/mL was
      strongly predictive of duodenal histology of Marsh grade 3a and higher with
      sensitivity, specificity, positive predictive value, and negative predictive
      value of 95.4 %, 98 %, 93.8 %, and 88.3 % respectively. CONCLUSIONS: There is a
      significant correlation between IgA anti-tTG titers and anthropometric parameters
      and severity of duodenal histopathology. With further validation, strongly
      positive titers may be sufficient to predict severity of this disease.

PMID- 24859394
TI  - Hepatitis C virus infection mediates cholesteryl ester synthesis to facilitate
      infectious particle production.
AB  - Cholesterol is a critical component of the hepatitis C virus (HCV) life cycle, as
      demonstrated by its accumulation within infected hepatocytes and lipoviral
      particles. To cope with excess cholesterol, hepatic enzymes ACAT1 and ACAT2
      produce cholesteryl esters (CEs), which are destined for storage in lipid
      droplets or for secretion as apolipoproteins. Here we demonstrate in vitro that
      cholesterol accumulation following HCV infection induces upregulation of the ACAT
      genes and increases CE synthesis. Analysis of human liver biopsy tissue showed
      increased ACAT2 mRNA expression in liver infected with HCV genotype 3, compared
      with genotype 1. Inhibiting cholesterol esterification using the potent ACAT
      inhibitor TMP-153 significantly reduced production of infectious virus, but did
      not inhibit virus RNA replication. Density gradient analysis showed that TMP-153
      treatment caused a significant increase in lipoviral particle density, suggesting
      reduced lipidation. These data suggest that cholesterol accumulation following
      HCV infection stimulates the production of CE, a major component of lipoviral
      particles. Inhibition of CE synthesis reduces HCV particle density and
      infectivity, suggesting that CEs are required for optimal infection of
      hepatocytes. 

PMID- 24859395
TI  - Divergent perceptions in health-related quality of life between family members
      and patients with rheumatoid arthritis, systemic lupus erythematosus, and
      ankylosing spondylitis.
AB  - The aim of this study was to assess whether family members perceive health
      related quality of life (HRQoL) of family members with rheumatic illnesses
      differently from the perceptions of these patients themselves. Cross-sectional
      study of consecutive patients with systemic lupus erythematosus (SLE), rheumatoid
      arthritis (RA), and ankylosing spondylitis (AS) attending two outpatient
      rheumatic clinics. HRQoL was assessed using the Spanish version of the World
      Health Organization Disability Assessment Scale (WHODAS-II) questionnaire; the
      "proxy" version is available for relatives. All patients and one proxy per
      patient separately answered the questionnaire at the clinic. Differences were
      determined by coefficients of determination (r (2)), Z scores, and meaningful
      differences of 30 %. Two hundred and ninety-one patients (111 SLE, 100 RA, and 80
      AS) and their respective proxies were included. The mean age was 35 +/- 13 years
      in SLE, 49.5 +/- 14 years in RA, and 40 +/- 14 years in AS patients. Divergent
      perceptions between patients and their proxies were found in 57 % of the SLE
      group, in 69 % of the RA group, and in 47 % of the AS group as per WHODAS-II
      global score. Stronger disagreement occurred for all the three groups in domains
      representing cognition and interaction with other people: around 60 % in the SLE
      group, 80 % in the RA group, and 40 % in the AS group. A substantial proportion
      of family members perceived the HRQoL of rheumatic family members differently
      from the perception of the patients themselves, most of the time biased toward
      underestimation, suggesting problems in the dynamics of efficient communication
      and social support. 

PMID- 24859396
TI  - The first case of acinic cell carcinoma of the breast within a fibroadenoma: case
      report.
AB  - A case of acinic cell carcinoma of the breast is reported in a 26-year-old woman.
      She presented a lump in her right breast, that seemed to be a fibroadenoma. The
      open biopsy revealed a well-bordered fibroadenoma, together with a proliferation
      of cells characterized by serous acinar differentiation and eosinophilic
      cytoplasmic granules. Tumor cells stained for amylase, lysozyme, alpha-1
      antichymotripsin, epithelial membrane antigen, S-100 protein, pan-cytokeratin,
      cytokeratin 7 and E-cadherin. Estrogen receptor, progesterone receptor, human
      epidermal growth factor receptor 2 overexpression, CD10, P63, smooth muscle
      actin, cytokeratin 5/6 were negative. The sentinel node was negative. 8 months
      after surgery she is in good clinical conditions without recurrence or
      metastases. 

PMID- 24859397
TI  - Small cell lung cancer associated with solitary fibrous tumors of the pleura: a
      case study and literature review.
AB  - INTRODUCTION: Small cell lung cancer (SCLC) is the most aggressive type of lung
      cancer. The surgical treatment is possible only in a few and defined occasions.
      The association between SCLC and a solitary fibrous tumor of pleura (SFTP) is
      extremely rare. CASE PRESENTATION: A 56 year-old man had a lung lesion (size 16
      mm) FDG-avid (SUV 7.9) within upper lobe of right lung. No lymph adenopathy or
      other distant lesion were found. The pathological results of FNAB showed the
      presence of malignant cells inconclusive for a definitive diagnosis. Following
      thoracotomy, the exploration of pleural cavity showed an unexpected lesion (size.
      3 cm) originating from parietal pleura and not radiologically seen. The
      intraoperative diagnosis was solitary fibrous tumor of the pleura. Then, an upper
      right lobectomy was achieved. The histological findings of the lung tumor
      diagnosed to be a SCLC (p-stage: T1N0M0). An adjuvant treatment was started. At
      20 months after the procedure, no recurrence was found. CONCLUSION: Surgery as
      part of multimodality treatment may be indicated in the treatment of SCLC in the
      early stage (T1N0M0). However, before proceeding to attend tumor resection an
      exploration of pleural cavity is mandatory in order to exclude any pleural
      involvement.

PMID- 24859398
TI  - Breast cancer micrometastasis and axillary sentinel lymph nodes frozen section.
      Our experience and review of literature.
AB  - BACKGROUND: Sentinel lymph node (SLN) biopsy plays a major role in the surgical
      management of primary breast cancer. The aim of this study was to assess the
      diagnostic accuracy of the assessment of axillary frozen sections of SLNs for
      micrometastasis diagnosis. PATIENTS AND METHODS: This study focused on 250 SLNs
      from 137 patients. Each lymph node was fully analyzed by frozen section. After
      fixation, serial sections were cut and stained by hematoxylin and eosin (HE) and
      for pan-cytokeratins by immunohistochemistry (IHC). RESULTS: Tumor cells were
      detected in 57 SLNs, 37 on frozen sections and 20 on controls. Of these 57
      positive SLNs, 38 contained metastases, 9 contained micrometastases and 10
      contained isolated tumor cells. The specificity and positive predictive value of
      SLN frozen sections for micrometastasis was 100%. The sensitivity was 83.3% for
      metastasis, 40% for micrometastasis; the false-negative rate was 16.7% for
      metastasis and 60% for micrometastasis. CONCLUSION: Analysis of frozen section of
      SLNs is an accurate method for metastasis detection, allowing concurrent axillary
      dissection when positive. The protocol for SLN analyses described herein shows
      good sensitivity for micrometastasis detection.

PMID- 24859399
TI  - Surgical management of acutely presenting gastrointestinal stromal tumors of the
      stomach among elderly: experience of an emergency surgery department.
AB  - INTRODUCTION: The incidence of gastrointestinal stromal tumors (GISTs), requiring
      often an emergency surgical management, is extremely rare among elderly. We aimed
      to present the experience of the Emergency Surgery Department, Brotzu Hospital,
      in the management of elderly patients with GIST related emergencies. METHODS:
      This study was carried out on 12 patients with gastrointestinal stromal tumors
      who presented to in an emergency situation during the period from January 2010 to
      December 2013. All patients' data, clinical presentations, surgical procedures,
      complications, and survival data were collected and analyzed. RESULTS: Between
      2010 and 2013, 12 patients (8 males and 4 females), with a mean age of 70 years
      (range: 65-79 years) were admitted with different emergency presentations of
      clinically and radiologically suspected GISTs. The incidence of proximal
      obstruction was 41.7% of all gastric GIST cases, resulting acute gastrointestinal
      bleeding and perforation in 41.7% and 16.6% respectively. The mean length of
      hospitalization was 9.1 +/- 2.3 days and there were no posterative complications
      or mortalities. At a mean follow-up of 21 months, 11 patients (91.6%) were alive
      and disease free. DISCUSSIONS: Although GISTs are uncommon among elderly, their
      incidence is increasing especially in their emergency presentation and surgeon
      should be prepared to treat this condition following the principles of GIST
      surgery as stated by the GIST consensus conference. CONCLUSIONS: In conclusion
      our data demonstrate that age itself does not affect the outcome of surgical
      treatment of GISTs in emergency situation.

PMID- 24859400
TI  - Staple line as a cause of unusual early internal hernia after appendectomy.
AB  - The use of mechanical stapling devices in laparoscopic appendectomies has become
      a common practice. Occasionally, the retained staples have been described to
      cause adhesions that might result in bowel obstruction. Early bowel obstruction
      after routine abdominal surgery should be closely investigated and might warrant
      early re-exploration. We present a rare case of small bowel obstruction caused by
      a staple line adhesive band one week after appendectomy. A 46-year-old female
      underwent laparoscopic appendectomy for uncomplicated appendicitis. A linear
      endoscopic stapling device was utilized during the procedure. The patient was
      discharged without complication. One week later, the patient presented to the
      emergency room for abdominal pain and she was discharged after adequate pain
      control. Several hours later she returned with similar symptoms, and she was
      diagnosed with distal small bowel obstruction by computed tomography scan. During
      the diagnostic laparoscopy there was an internal hernia through a defect created
      by the appendiceal staple line and the adjacent small bowel mesentery. After
      reduction of the hernia, the small bowel venous drainage improved, and no
      intestinal resection was necessary. The offending staple was removed and the
      staple line covered with omentum. The patient had complete resolution of symptoms
      and she was discharged the following day. No perioperative complications
      occurred. Mechanical staplers are routinely used in laparoscopic appendectomy.
      The staple line should be inspected at the end of the procedure to confirm the
      absence of free, unformed staples that can generate adhesions and postoperative
      complications. 

PMID- 24859401
TI  - Gastroesophageal reflux disease and obesity: do we need to perform reflux testing
      in all candidates to bariatric surgery?
AB  - INTRODUCTION: Obesity is a strong independent risk factor of gastroesophageal
      reflux disease (GERD) symptoms and esophageal erosions. However the relationship
      between obesity and GERD is still a subject of debate. In fact, if in most cases
      bariatric surgery can diminish reflux by losing a large amount of fat, on the
      other hand some restrictive procedure can worsen or cause the presence of GERD.
      Thus, it is unclear if patients candidate to bariatric surgery have to perform
      pre-operative reflux testing or not. AIM: of the study was to verify the presence
      of GERD patterns in patients candidate to surgery and the need of pre-operative
      reflux testing. METHODS: All patients underwent to a standardized questionnaire
      for symptoms severity (GERQ), upper endoscopy, high resolution manometry (HRiM)
      and impedance pH-monitoring (MII-pH). Patients were stratified into: group 1
      (negative for both GERQ and endoscopy), group 2 (positive for GERQ and negative
      for endoscopy), group 3 (positive for both GERQ and endoscopy). A healthy
      volunteers group (HV) was assessed. RESULTS: One hundred thirty-nine subjects
      (obese, 124; HV normal weight, 15) were studied. Group 1 showed comparable mean
      LES pressure, peristaltic function, bolus transport and presence of hiatal hernia
      than HV. Group 2 showed a reduction of these parameters, while group 3 showed a
      statistical significant reduction in LES pressure, peristaltic function, bolus
      transport and increase in presence of hiatal hernia. At MII-pH, Group 1 showed a
      not significant increase in reflux patterns; group 2 and 3 showed a significant
      increase in esophageal acid exposure and in number of refluxes (both acid and
      weakly acid), with group 3 showing the higher grade of reflux pattern.
      CONCLUSIONS: Obese subjects with pre-operative presence of GERD symptoms and
      endoscopical signs could be tested with HRM and MII-pH before undergoing
      bariatric surgery, especially for restrictive procedures. On the other hand,
      obese patients without any sign of GERD could not be tested for reflux, showing
      similar patterns to HV.

PMID- 24859402
TI  - Relationship between postoperative venous thromboembolism and hemorrhage in
      patients undergoing total thyroidectomy without preoperative prophylaxis.
AB  - INTRODUCTION: The aim of the present study was to critically review the incidence
      of venous thromboembolism and postoperative hemorrhage in patients undergoing
      total thyroidectomy without preoperative prophylaxis. METHODS: A prospective
      electronic database of all patients undergoing total thyroidectomy over a six
      year period within August 2013 in our medical unit was analyzed. The incidence of
      postoperative bleeding and Venous thromboembolism (VTE) was reviewed by
      subgrouping all patients according to a risk factor score (RFS) for VTE as
      outlined in the American College of Surgeons National Surgical Quality
      Improvement Program (ACS NSQIP) Best Practice Guidelines. RESULTS: An overall
      1018 consecutive patients [244 men (24%, mean age 46 +/- 13 years), 778 women
      (76%, mean age 44 +/- 17 years)] underwent total thyroidectomy. Postoperative
      bleeding occurred in 8/1018 patients (0.8%). One out of 1018 (0.1%) patients also
      subcategorized according to the RFS had VTE. The incidence of VTE complication in
      the entire population was lower than the risk of postoperative bleeding (P <
      .0001). CONCLUSION: The risk of developing VTE in patients who undergo total
      thyroidectomy for benign and malignant diseases without preoperative prophylaxis
      is roughly 8-fold less than developing a potentially life threatening
      complication as postoperative bleeding. Until large well conducted prospective
      studies on the impact of preoperative prophylaxis on postoperative VTE and
      bleeding will clarify the issue, it is conceivable to propose the use of
      stockings and/or anticoagulants according to the individual patient risk factors.

PMID- 24859404
TI  - Meso-pancreatectomy for pancreatic neuroendocrine tumor.
AB  - We report a case of a meso-pancreatectomy performed on a pancreatic glucagonoma
      in a 58 years-old woman. MP is a conservative surgical treatment consisting in a
      resection of the body of the pancreas with the aim of reducing postoperative
      hormone insufficiency. This approach is curative in benign or low-malignant
      neoplasm of the central part of the pancreas. 

PMID- 24859403
TI  - Acellular bovine pericardium dermal matrix in immediate breast reconstruction
      after Skin Sparing Mastectomy.
AB  - INTRODUCTION: Mastectomy for breast cancer may bring the patient to develop long
      term issues concerning the psychological and physical status. Immediate breast
      reconstruction (IBR) should be considered and proposed by physicians as an
      integrated procedure in the surgical approach to breast cancer to reduce further
      surgery. Acellular dermal matrix (ADM) has been used in revision breast
      reconstruction for fold malposition, capsular contracture and rippling also,
      showing good outcomes with low risk of complications. Aim of this study was to
      verify if the known advantages in using ADM for IBR would led to lower rates of
      seroma formation, infection, skin flap necrosis and overall complication related
      to the implant. METHODS: We performed a prospective study, including all
      consecutive patients undergone to IBR with biological graft with ADM between
      January 2012 and January 2013 at our Institution. Data on major issues of the
      patients and complications were recorded. All patients underwent to IBR with ADM
      (Tutomesh) implant with or without fibrin sealant positioning. RESULTS: A total
      of 24 patients underwent 28 immediate breast reconstruction with Tutomesh ADM
      implant. Main postoperative complications included seroma formation in 20.8% (5
      pts), infection in 8.3% (2 pts) and hematoma in 4.2% (1 pt). There were any skin
      flap necrosis in the study. Diabetes was associated in two cases with edema and
      ecchymosis; hypertension with infection in one case (implant removal) and seroma
      in one case. First class of obesity (BMI 30-32.7) was associated with seroma in 3
      cases, and with infection in one. In patient without fibrin sealant (12 patients 
      13 breasts) complications were represented by hematoma (1 pt. 4.2%), infection
      (1 pt. 4.2%; implant removal) and seroma (4 pts 16.8%). CONCLUSIONS: The use of
      Tutomesh((r)) bovine pericardium for immediate breast is safe and technically
      useful. Complications rate is not high, except for seroma formation that can be
      reduced by the contemporary use of fibrin sealant.

PMID- 24859405
TI  - Staples versus subcuticular closure in cervicotomy incisions.
AB  - Collar transverse incision is the typical surgical access for operations on
      thyroid and parathyroids. The cosmetic outcome resulting from its closure is of
      paramount importance given its anatomical exposure. The traditional methods of
      closure include metal clips, subcuticular stitch and glue. In this study we
      evaluated the cosmetic results on 10 patients who had their cervicotomy wound
      closed with clips comparing it to a second group of 10 patients who had the same
      incision closed with subcuticular stitch. The cosmetic outcome was evaluated with
      a questionnaire answered by the patients, by the operating surgeon and by a
      surgical nurse who was blinded to the technique used. The results of the
      questionnaire were grossly similar with no differences in the two groups. Only
      two complications were recorded in the subcuticular group. Both the techniques
      associate to similar cosmetic outcome, and the choice between the two should be
      left to the surgeon's personal preference. 

PMID- 24859406
TI  - Acinic cell carcinoma of the breast: review of the literature.
AB  - INTRODUCTION: The breast and salivary gland tissue share embryologic and thus
      pathological similarities. Acinic cell carcinoma (ACC) is a typical tumor in
      salivary glands, but rarely arises in breast too. We reviewed 38 cases of mammary
      ACC reported in literature and our case, the first ACC born within a
      fibroadenoma. MATERIALS AND METHODS: Data were collected by a research for the
      key words acinic cell carcinoma breast on Pubmed in March 2014, including a case
      treated in our department. All reviewed cases were compared for clinical approach
      and histological pattern. RESULTS: To date 23 articles presenting cases of ACC of
      the breast are reported in literature. We included in our review 38 cases
      previously described and one new case. The histological pattern was predominantly
      solid with a microglandular structure. All the tumor cells were cytologically
      characterized by monotonous round cells with a finely granular, weakly
      eosinophilic, or clearly vacuolated cytoplasm. The most of the cells were
      intensely stained with anti-lysozime, anti-amylase, anti-alpha1-chimotripsin,
      anti-EMA and anti-S100 protein antisera. Immunohistochemistry was also performed
      to point out: estrogen receptor (ER), progesterone receptor (PR), androgen
      receptors (AR), human epidermal growth factor receptor 2 overexpression
      (HER2/neu), E-cadherin (E-cad), cytokeratin-7 (CK7), gross cystic disease fluid
      protein 15 (GCDFP15), smooth muscle actin (SMA). CONCLUSION: ACC of the breast is
      a rare tumor, showing similarities with the salivary gland counterpart, above all
      in terms of good prognosis, and differences from the ordinary invasive breast
      carcinoma. Further investigations are needed to elucidate the true histogenesis
      and the correct treatment.

PMID- 24859407
TI  - Postoperative hypocalcemia: assessment timing.
AB  - 180 total thyroidectomy case studies performed by the same operator in the years
      2006-2010, all done with sutureless technique (Ligasure precise((r))). The
      monitoring of patients involved a dose of serum calcium on the 1st, 2nd, 3rd and
      seventh post-operative, before the ambulatory monitoring of the patient.
      Treatment of post-operative thyroidectomy also includes the administration from
      the first day of post-surgery, of 2 g/day of calcium (calcium lactate gluconate
      2940 mg, calcium carbonate 300 mg). Hypocalcemia was observed in 27 cases (15%)
      of which 23/180 (12.8%) were transitional and 4/180 (2.2%) were permanent. The
      average postoperative hospitalization was 2.5 days with a minimum of 30 h. The
      peak of hypocalcemia was of 11 patients on the first postoperative day (40.7%) in
      6 patients on the second postoperative day (22.2%), in 8 patients on the third
      postoperative day (29.6%), in 1 patient on the fourth postoperative day (3.7%)
      and in another one on the fifth postoperative day (3.7%). The second
      postoperative day is crucial for the determination of early discharge (24-30 h).
      When the surgeon identifies and manages to preserve at least 3 parathyroid glands
      during surgery, the risk of hypocalcemia together with evaluations of serum
      calcium on the first and second post-operative day, eliminates the hypocalcemic
      risk. 

PMID- 24859408
TI  - Clinical outcome in differentiated thyroid carcinoma and microcarcinoma.
AB  - INTRODUCTION: Due to the frequent use of neck ultrasonography, the incidence of
      differentiated thyroid microcarcinoma (DTMC), defined as a lesion with greatest
      dimension <=1 cm, is increasing worldwide. Although DTMC generally has a lower
      aggressivity and a better prognosis than differentiated thyroid carcinoma (DTC),
      some cases of clinically aggressive DTMC were found. The aim of this study is to
      compare the rate of recurrence in DTMC and DTC, during a 3-year follow-up.
      METHODS: Patients with differentiated thyroid carcinoma, who underwent total
      thyroidectomy and postoperative (131)I-RAI ablation, were stratified according to
      lesion diameter (DTC for diameter > 1 cm or DTMC <= 1 cm). After surgery,
      patients underwent a 3-year follow-up. Recurrent disease was defined on the basis
      of positive biochemical (Tg > 2 ng/ml under TSH-suppression or after rhTSH
      stimulation) and/or imaging (US, WBS, CT, PET/CT) findings. RESULTS: 449 patients
      have been included in the final analysis. Linfoadenectomy rate and RAI ablative
      dose were significantly higher in DTC than in DTMC (32.7% vs. 22.4%, p = 0.018
      and 112.3 +/- 21 vs. 68.3 +/- 24.1 mCi, p < 0.001). During the follow-up, 50
      carcinoma recurrences occurred, more frequent in DTC than in DTMC (15.6% vs.
      7.6%, p = 0.010). After adjustment for gender, age, rate of lymph node dissection
      and 131I dose of RAI treatment, the difference in the risk of recurrence was no
      longer significant among DTC and DTMC patients (HR: 1.585, 95% CI 0874-2877, p =
      0.130). CONCLUSIONS: The prediction of disease severity cannot be based
      exclusively on lesion diameter. A more careful therapeutic approach and follow-up
      should be recommended in DTMC patients.

PMID- 24859409
TI  - Controversies in the surgical management of thyroid follicular neoplasms.
      Retrospective analysis of 721 patients.
AB  - The most appropriate surgical management of "follicular neoplasm/suspicious for
      follicular neoplasm" lesions, is still controversial. Analysing and comparing the
      experience of two units for endocrine surgery, we retrospectively evaluated 721
      patients, surgically treated after a follicular neoplasm diagnosis. Total
      thyroidectomy was routinely performed in one Institution, while in the other one
      it was selectively carried out. The main criteria leading to hemythyroidectomy
      were a single nodule, the age <=45 years, the absence of thyroiditis or
      clinical/intraoperative suspicion of malignancy. Total thyroidectomy was
      performed in 402/721 patients (55.7%), hemythyroidectomy in 319/721 cases (44.2%)
      and a completion thyroidectomy in 51/319 cases (15.9%). The overall malignancy
      rate was 24% (176/721 patients), respectively 16% (51/319 patients) following
      hemythyroidectomy, and 31% (125/402 patients) following total thyroidectomy.
      Definitive recurrent laryngeal nerve paralysis and permanent hypoparathyroidism
      were not reported in hemythyroidectomy patients in which lower mean
      hospitalization and costs were observed. Considering the low-risk of follicular
      neoplasm solitary lesions, hemythyroidectomy is still the safest standard of care
      with lower hospitalization and costs. In case of multiglandular disease or
      thyroiditis, that might be associated with a higher risk of cancer, total
      thyroidectomy should be recommended. Further investigation is warranted to
      achieve a better preoperative follicular neoplasm diagnostic accuracy in order to
      reduce the amount of unnecessary surgical operations with a diagnostic aim. 

PMID- 24859410
TI  - Sutureless thyroidectomy.
AB  - OBJECTIVE: The ultrasonic scalpel is a surgical shear that uses high-frequency
      mechanical energy to enable simultaneous vessel sealing and tissue coagulation at
      the same time. We conducted a prospective study to compare the outcome of total
      thyroidectomy using the ultrasonic scalpel versus the device Ligasure in terms of
      safety, operative time, overall drainage volume, complications, hospital stay.
      METHODS: Between January 2008 and December 2013,400 patients (260 women, 140 men;
      mean age 46 years) undergoing thyroidectomy were randomized into two groups:
      group A, where Ultracision were used, and group B, where the Ligasure device was
      used. RESULTS: There was no significant differences between the two groups in
      terms of age, gender, indication for thyroidectomy, thyroid gland weight and
      diameter, histopathologic diagnosis, preoperative and postoperative serum calcium
      levels, postoperative complications and reoperative thyroid surgery, time of
      operation and amount of drainage. CONCLUSIONS: The ultrasonic scalpel and the
      Ligasure ares safe, effective, useful, and time-saving alternative to the
      traditional suture ligation technique for thyroid surgery. They simplified total
      thyroidectomy, eliminating the need for clamp-and-tie maneuvers while achieving
      efficient hemostasis.

PMID- 24859411
TI  - Extrathoracic recurrence of type A thymoma.
AB  - INTRODUCTION: Neoplasms of the thymus gland are the most common tumors in the
      anterior mediastinum, and differentiation between benign and malignant forms is
      rather difficult. Extrathoracic invasions or metastases are extremely rare, and
      only a few cases have been reported previously. CASE PRESENTATION: We report
      herein the case of a patient in whom a thymoma type A recurred at skeletal muscle
      2-years after surgery. The metastases were completely resected. Adjuvant
      treatment was started. Actually, no signs of recurrence were seen. CONCLUSION:
      Our case shows that also thymoma type A, generally defined as a low malignancy,
      may recur. Thus, a strict follow-up is required. If metastases are present,
      surgical resection with curative intent associated with adjuvant therapy should
      be attended.

PMID- 24859413
TI  - Total reproductive values for females and for males in sexual diploids are not
      equal.
AB  - A very simple mathematical exposition of reproductive value in an age- and sex
      structured sexual diploid population employs reproductive value as the
      probability that a random gene in a distant generation traces its ancestry to a
      given individual or set of individuals today. Although the total reproductive
      values of all females and that of all males are not in general equal, but instead
      proportional to the average age of a new mother and a new father, respectively,
      Fisher's equal-investment conclusion for the sex ratio remains valid because the
      total reproductive value of age-zero females equals the total reproductive value
      of age-zero males. However, the conclusion is seen to require an extra
      assumption, namely stability of the age-distribution. 

PMID- 24859412
TI  - Metformin sensitizes chemotherapy by targeting cancer stem cells and the mTOR
      pathway in esophageal cancer.
AB  - Our clinical study indicates esophageal adenocarcinoma patients on metformin had
      a better treatment response than those without metformin. However, the effects of
      metformin and the mechanisms of its action in esophageal cancer (EC) are unclear.
      EC cell lines were used to assess the effects of metformin alone or in
      combination with 5-fluorouracil on survival and apoptosis. RPPA proteomic array
      and immunoblots were used to identify signaling affected by metformin. Standard
      descriptive statistical methods were used. Reduction in cell survival and
      induction of apoptosis by metformin were observed in several EC cell lines. The
      use of metformin in combination with 5-FU significantly sensitized EC cells to
      the cytotoxic effect of 5-FU. RPPA array demonstrated that metformin decreased
      various oncogenes including PI3K/mTORsignaling and survival/cancer stem cell
      related genes in cells treated with metformin compared with its control.
      Immunoblots and transcriptional analyses further confirm that metformin
      downregulated these CSC-related genes and the components of the mTOR pathway in a
      dose-dependent manner. Sorted ALDH-1+ cell tumor sphere forming capacity was
      preferentially reduced by metformin. Finally, metformin reduced tumor growth in
      vivo and when combined with FU, there was synergistic reduction in tumor growth.
      Metformin inhibits EC cell growth and sensitizes EC cells to 5-FU cytotoxic
      effects by targeting CSCs and the components of mTOR. The present study supports
      our previous clinical observations that the use of metformin is beneficial to EC
      patients. Metformin can complement other therapeutic combinations to effectively
      treat EC patients.

PMID- 24859414
TI  - Bioinformatic analysis revealing association of exosomal mRNAs and proteins in
      epigenetic inheritance.
AB  - Transgenerational inheritance of environment induced phenotype requires
      transmission of epigenetic information through the germline. Whereas several
      epigenetic factors have been implicated in germline transmission, mediators of
      information transfer from soma to the germline remain unidentified in mammals.
      Notably, a recent bioinformatic analysis showed association of extracellular
      microRNAs (miRNAs) and altered transcriptomes in diverse instances of mammalian
      epigenetic inheritance involving different environmental factors, tissues, life
      cycle stages, generations and genders. It was predicted that regulatory non
      coding RNAs (ncRNAs) may potentially mediate soma to germline information
      transfer. Remarkably, the present bioinformatic evidence suggests similar
      association of exosomal mRNAs and proteins. The differentially expressed genes
      reported previously in genome level expression profiling studies related to or
      relevant in epigenetic inheritance showed enrichment for documented set of
      exosomal mRNAs in a few instances of epigenetic inheritance and of exosomal
      proteins in a majority of instances. Differentially expressed genes encoding
      exosomal miRNAs and proteins, directly or indirectly through first and/or second
      degree interactome networks, overrepresented biological processes related to
      environmental factors used in these instances as well as to epigenetic
      alterations, especially chromatin and histone modifications. These findings
      predict that exosomal mRNAs and proteins, like extracellular miRNAs, may also
      potentially mediate soma to germline information transfer. A convergent
      conceptual model is presented wherein extracellular ncRNAs/miRNA, mRNAs and
      proteins provide the much needed continuum inclusive of epigenetic inheritance.
      The phrase "transgenerational systems biology" is introduced to signify that the
      realm of systems biology extends beyond an individual organism and encompasses
      generations. 

PMID- 24859416
TI  - Recurrent Focal myositis: a rare inflammatory myopathy.
AB  - Focal myositis is an acute and localized muscle inflammation of unknown
      aetiology. The clinical diagnosis is often difficult to obtain, since it can be
      confused with infections, vascular thrombosis or muscle tumours such as sarcomas.
      This leads to a significant delay in the diagnosis, resulting in the
      administration of inappropriate and potentially harmful treatments.  We report
      here a case of recurrent focal myositis in a woman where the diagnosis was only
      obtained after 6 years, despite multiple hospital admissions. This case
      reinforces the importance of clinical knowledge and experience to tackle
      challenging medical scenarios. 

PMID- 24859415
TI  - Screening of hyaluronic acid-poly(ethylene glycol) composite hydrogels to support
      intervertebral disc cell biosynthesis using artificial neural network analysis.
AB  - Hyaluronic acid (HA)-poly(ethylene glycol) (PEG) composite hydrogels have been
      widely studied for both cell delivery and soft tissue regeneration applications.
      A very broad range of physical and biological properties have been engineered
      into HA-PEG hydrogels that may differentially affect cellular "outcomes" of
      survival, synthesis and metabolism. The objective of this study was to rapidly
      screen multiple HA-PEG composite hydrogel formulations for an effect on matrix
      synthesis and behaviors of nucleus pulposus (NP) and annulus fibrosus (AF) cells
      of the intervertebral disc (IVD). A secondary objective was to apply artificial
      neural network analysis to identify relationships between HA-PEG composite
      hydrogel formulation parameters and biological outcome measures for each cell
      type of the IVD. Eight different hydrogels were developed from preparations of
      thiolated HA (HA-SH) and PEG vinylsulfone (PEG-VS) macromers, and used as
      substrates for NP and AF cell culture in vitro. Hydrogel mechanical properties
      ranged from 70 to 489kPa depending on HA molecular weight, and measures of matrix
      synthesis, metabolite consumption and production and cell morphology were
      obtained to study relationships to hydrogel parameters. Results showed that NP
      and AF cell numbers were highest upon the HA-PEG hydrogels formed from the lower
      molecular-weight HA, with evidence of higher sulfated glycosaminoglycan
      production also upon lower-HA-molecular-weight composite gels. All cells formed
      more multi-cell clusters upon any HA-PEG composite hydrogel as compared to
      gelatin substrates. Formulations were clustered into neurons based largely on
      their HA molecular weight, with few effects of PEG molecular weight observed on
      any measured parameters. 

PMID- 24859417
TI  - Insulin-like growth factors in embryonic and fetal growth and skeletal
      development (Review).
AB  - The insulin-like growth factors (IGF)-I and -II have a predominant role in fetal
      growth and development. IGFs are involved in the proliferation, differentiation
      and apoptosis of fetal cells in vitro and the IGF serum concentration has been
      shown to be closely correlated with fetal growth and length. IGF transcripts and
      peptides have been detected in almost every fetal tissue from as early in
      development as pre-implantation to the final maturation stage. Furthermore, IGFs
      have been demonstrated to be involved in limb morphogenesis. However, although
      ablation of Igf genes in mice resulted in growth retardation and delay in
      skeletal maturation, no impact on outgrowth and patterning of embryonic limbs was
      observed. Additionally, various molecular defects in the Igf1 and Igf1r genes in
      humans have been associated with severe intrauterine growth retardation and
      impaired skeletal maturation, but not with truncated limbs or severe skeletal
      dysplasia. The conflicting data between in vitro and in vivo observations with
      regard to bone morphogenesis suggests that IGFs may not be the sole trophic
      factors involved in fetal skeletal growth and that redundant mechanisms may exist
      in chondro- and osteogenesis. Further investigation is required in order to
      elucidate the functions of IGFs in skeletal development. 

PMID- 24859418
TI  - COX2 expression in neuroblastoma increases tumorigenicity but does not affect
      cell death in response to the COX2 inhibitor celecoxib.
AB  - COX2 is an inducible cyclooxygenase implicated in the metastasis and migration of
      tumour cells. In neuroblastoma, COX2 expression has been detected in both cell
      lines and tumours. The treatment of neuroblastoma cells in vitro with celecoxib,
      a COX2 inhibitor, induces apoptosis. The aim of this study was to investigate the
      role of COX2 in neuroblastoma tumour biology by creating a cell line in which
      COX2 could be conditionally expressed. Xenograft studies showed that the
      conditional expression of COX2 enhanced tumour growth and malignancy. Elevated
      COX2 expression enhanced the proliferation and migration of neuroblastoma cells
      in vitro. However, elevated COX2 expression or variation between cell lines did
      not affect sensitivity to the COX2 inhibitor celecoxib, indicating that celecoxib
      does not promote cell death through COX2 inhibition. These data show that
      increased COX2 expression alone can enhance the tumorigenic properties of
      neuroblastoma cells; however, high levels of COX2 may not be a valid biomarker of
      sensitivity to non-steroidal anti-inflammatory drugs such as celecoxib. 

PMID- 24859420
TI  - The 12th Annual Pharmacogenetics in Psychiatry meeting report.
AB  - The 12th Annual Pharmacogenetics in Psychiatry meeting was held in Hollywood,
      Florida, from 31 May to 1 June 2013, in conjunction with the NCDEU meeting. It
      included a series of oral presentations as well as a poster session. This report
      summarizes the presentations at the conference. 

PMID- 24859419
TI  - High resolution genetic mapping uncovers chitin synthase-1 as the target-site of
      the structurally diverse mite growth inhibitors clofentezine, hexythiazox and
      etoxazole in Tetranychus urticae.
AB  - The acaricides clofentezine, hexythiazox and etoxazole are commonly referred to
      as 'mite growth inhibitors', and clofentezine and hexythiazox have been used
      successfully for the integrated control of plant mite pests for decades. Although
      they are still important today, their mode of action has remained elusive.
      Recently, a mutation in chitin synthase 1 (CHS1) was linked to etoxazole
      resistance. In this study, we identified and investigated a Tetranychus urticae
      strain (HexR) harboring recessive, monogenic resistance to each of hexythiazox,
      clofentezine, and etoxazole. To elucidate if there is a common genetic basis for
      the observed cross-resistance, we adapted a previously developed bulk segregant
      analysis method to map with high resolution a single, shared resistance locus for
      all three compounds. This finding indicates that the underlying molecular basis
      for resistance to all three compounds is identical. This locus is centered on the
      CHS1 gene, and as supported by additional genetic and biochemical studies, a non
      synonymous variant (I1017F) in CHS1 associates with resistance to each of the
      tested acaricides in HexR. Our findings thus demonstrate a shared molecular mode
      of action for the chemically diverse mite growth inhibitors clofentezine,
      hexythiazox and etoxazole as inhibitors of an essential, non-catalytic activity
      of CHS1. Given the previously documented cross-resistance between clofentezine,
      hexythiazox and the benzyolphenylurea (BPU) compounds flufenoxuron and
      cycloxuron, CHS1 should be also considered as a potential target-site of
      insecticidal BPUs. 

PMID- 24859422
TI  - Multiple bout rTMS on spatial working memory: a comparison study of two cortical
      areas.
AB  - It has been established that acute (within-session) repetitive transcranial
      magnetic stimulation (rTMS) improves spatial working memory (SWM). However,
      questions remain regarding the safety and effectiveness of multiple bouts of rTMS
      and the optimal cortical area to stimulate. This preliminary study investigated,
      in healthy participants, multiple bouts of rTMS over the dorsolateral pre-frontal
      cortex (DLPFC), or posterior parietal cortex (PPC) on SWM. Twenty participants
      (10m, 10f), all naive to rTMS, where randomized into a DLPFC or PPC group,
      receiving six sessions of rTMS (5Hz at 80% of motor threshold) every second day
      over two weeks. Prior to and post rTMS bouts, all participants completed testing
      for SWM measuring individuals' accuracy, strategy, and speed. Following repeated
      bouts of rTMS, significant improvements were observed with no contraindications
      in stimulating PPC but not DLPFC. This preliminary study has demonstrated that
      repeated rTMS bouts improve SWM safety providing potential for clinical
      application. 

PMID- 24859421
TI  - A new porcine reproductive and respiratory syndrome virus strain with highly
      conserved molecular characteristics in its parental and attenuated strains.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) causes substantial
      economic losses to many swine-producing regions. In this study, PRRSV strain
      NT0801-F80 was derived from its parental isolate NT0801 by 80 passages in Marc
      145 cells. Experimental infection of piglets clearly demonstrated that strain
      NT0801-F80 is less virulent than NT0801. However, whole genome sequencing showed
      that the genomes of the parental and attenuated strains are highly conserved
      compared with those of four other pairs of virulent parental/attenuated vaccine
      strains (VR2332 and RespPRRS MLV, JA142 and Ingelvac((r)) ATP MLV, CH-1a and CH
      1R, and JXA1 and JXAR). The attenuated strain NT0801-F80 has only 21 nucleotide
      changes, producing only 14 amino acid changes in NSP2, GP2, GP3, and GP5,
      compared with those aa sequences of the virulent parental strain. These mutated
      aa in the attenuated virus may be involved in virulence. These data provide
      valuable information on the attenuation mechanism of PRRSV that should be useful
      in future research. 

PMID- 24859423
TI  - Automatic detection of orientation changes of faces versus non-face objects: a
      visual MMN study.
AB  - To investigate the automatic change detection of faces versus non-face objects,
      the visual mismatch negativity (vMMN) elicited by deviant orientation (90 degrees
      versus 0 degrees ) for faces and houses, respectively, was recorded using the
      deviant-standard-reversed paradigm. The present face stimuli elicited larger N170
      than did houses, regardless of the orientation. A larger and delayed N170 for
      deviant rotated faces was elicited than that for standard rotated faces, whereas
      the N170 did not differ between deviant and standard rotated houses. The rotated
      faces elicited increased vMMN amplitude and decreased vMMN latency than did the
      rotated houses. The face-MMN with a right occipito-temporal scalp distribution
      was larger for the rotated than upright conditions but the orientation did not
      modulate the amplitudes of house MMN. These data provided electrophysiological
      evidence for larger sensitivity for orientation changes of faces than those of
      objects even in the absence of attention, due to the disruption of configural
      processing caused by face rotation. 

PMID- 24859424
TI  - Is the ability to keep your mind sharp under pressure reflected in your heart?
      Evidence for the neurophysiological bases of decision reinvestment.
AB  - The aim of this study was twofold: first, to examine the influence of decision
      reinvestment on decision-making performance using an option-generation task, and
      second to investigate its neurophysiological basis with heart rate variability.
      Forty-two male participants performed an option-generation task (i.e., where
      participants are required to generate their own options rather than being asked
      to decide from a set of options) under low- and high-pressure conditions. Results
      showed that the decision-making performance of low and high decision reinvesters
      was similar in the low-pressure condition, however in the high-pressure condition
      low reinvesters decided faster than their high reinvester counterparts. Moreover,
      we found that the pressure-induced reduction in parasympathetic activity was more
      pronounced in high reinvesters in comparison to low reinvesters. Findings are
      interpreted in light of the neurovisceral integration model, assuming a positive
      relationship between cognitive performance and parasympathetic activity. These
      findings offer a physiological insight into a psychological phenomenon and may
      also suggest a way to counteract the detrimental effects of decision reinvestment
      by utilizing interventions that target the parasympathetic activity, such as
      heart rate variability biofeedback. 

PMID- 24859425
TI  - Decomposition rate of carrion is dependent on composition not abundance of the
      assemblages of insect scavengers.
AB  - Environmental factors and biodiversity affect ecosystem processes. As
      environmental change modifies also biodiversity it is unclear whether direct
      effects of environmental factors on ecosystem processes are more important than
      indirect effects mediated by changes in biodiversity. High-quality resources like
      carrion occur as heterogeneous pulses of energy and nutrients. Consequently, the
      distribution of scavenging insects is related to resource availability.
      Therefore, carrion decomposition represents a suitable process from which to
      unravel direct effects of environmental change from indirect biodiversity-related
      effects on ecosystem processes. During three field seasons in 2010 we exposed
      traps baited with small-mammal carrion at 21 sites along a temperature gradient
      to explore the insect carrion fauna and decomposition rate in the Bohemian
      Forest, Germany. The abundance component of beetle and fly assemblages decreased
      with decreasing temperature. Independently, the composition component of both
      taxa changed with temperature and season. The change in the composition component
      of beetles depicted a loss of larger species at higher temperatures.
      Decomposition rate did not change directly along the temperature gradient but was
      directly influenced by season. The composition component of beetles, and to a
      small extent of flies, but not their abundance component, directly affected
      carrion decomposition. Consequently, lower decomposition rates at lower
      temperatures can be explained by the absence of larger beetle species. Thus, we
      predict that future environmental change will modify carrion fauna composition
      and thereby indirectly decomposition rate. Moreover, reorganizations of the
      insect carrion composition will directly translate into modified decomposition
      rates, with potential consequences for nutrient availability and carbon storage. 

PMID- 24859427
TI  - Cancer initiation with epistatic interactions between driver and passenger
      mutations.
AB  - We investigate the dynamics of cancer initiation in a mathematical model with one
      driver mutation and several passenger mutations. Our analysis is based on a multi
      type branching process: we model individual cells which can either divide or
      undergo apoptosis. In the case of a cell division, the two daughter cells can
      mutate, which potentially confers a change in fitness to the cell. In contrast to
      previous models, the change in fitness induced by the driver mutation depends on
      the genetic context of the cell, in our case on the number of passenger
      mutations. The passenger mutations themselves have no or only a very small impact
      on the cell's fitness. While our model is not designed as a specific model for a
      particular cancer, the underlying idea is motivated by clinical and experimental
      observations in Burkitt Lymphoma. In this tumor, the hallmark mutation leads to
      deregulation of the MYC oncogene which increases the rate of apoptosis, but also
      the proliferation rate of cells. This increase in the rate of apoptosis hence
      needs to be overcome by mutations affecting apoptotic pathways, naturally leading
      to an epistatic fitness landscape. This model shows a very interesting dynamical
      behavior which is distinct from the dynamics of cancer initiation in the absence
      of epistasis. Since the driver mutation is deleterious to a cell with only a few
      passenger mutations, there is a period of stasis in the number of cells until a
      clone of cells with enough passenger mutations emerges. Only when the driver
      mutation occurs in one of those cells, the cell population starts to grow
      rapidly.

PMID- 24859426
TI  - Dose-dependent model of caffeine effects on human vigilance during total sleep
      deprivation.
AB  - Caffeine is the most widely consumed stimulant to counter sleep-loss effects.
      While the pharmacokinetics of caffeine in the body is well-understood, its
      alertness-restoring effects are still not well characterized. In fact,
      mathematical models capable of predicting the effects of varying doses of
      caffeine on objective measures of vigilance are not available. In this paper, we
      describe a phenomenological model of the dose-dependent effects of caffeine on
      psychomotor vigilance task (PVT) performance of sleep-deprived subjects. We used
      the two-process model of sleep regulation to quantify performance during sleep
      loss in the absence of caffeine and a dose-dependent multiplier factor derived
      from the Hill equation to model the effects of single and repeated caffeine
      doses. We developed and validated the model fits and predictions on PVT lapse
      (number of reaction times exceeding 500 ms) data from two separate laboratory
      studies. At the population-average level, the model captured the effects of a
      range of caffeine doses (50-300 mg), yielding up to a 90% improvement over the
      two-process model. Individual-specific caffeine models, on average, predicted the
      effects up to 23% better than population-average caffeine models. The proposed
      model serves as a useful tool for predicting the dose-dependent effects of
      caffeine on the PVT performance of sleep-deprived subjects and, therefore, can be
      used for determining caffeine doses that optimize the timing and duration of peak
      performance.

PMID- 24859428
TI  - The fuzzy oil drop model, based on hydrophobicity density distribution,
      generalizes the influence of water environment on protein structure and function.
AB  - In this paper we show that the fuzzy oil drop model represents a general
      framework for describing the generation of hydrophobic cores in proteins and thus
      provides insight into the influence of the water environment upon protein
      structure and stability. The model has been successfully applied in the study of
      a wide range of proteins, however this paper focuses specifically on domains
      representing immunoglobulin-like folds. Here we provide evidence that
      immunoglobulin-like domains, despite being structurally similar, differ with
      respect to their participation in the generation of hydrophobic core. It is shown
      that beta-structural fragments in beta-barrels participate in hydrophobic core
      formation in a highly differentiated manner. Quantitatively measured
      participation in core formation helps explain the variable stability of proteins
      and is shown to be related to their biological properties. This also includes the
      known tendency of immunoglobulin domains to form amyloids, as shown using
      transthyretin to reveal the clear relation between amyloidogenic properties and
      structural characteristics based on the fuzzy oil drop model. 

PMID- 24859430
TI  - Regular aquatic exercise for chronic kidney disease patients: a 10-year follow-up
      study.
AB  - Chronic kidney disease (CKD) patients not yet in dialysis can benefit from
      increased physical activity; however, the safety and outcomes of aquatic exercise
      have not been investigated in observational studies. The aim of this study was to
      analyze association of 10 years of regularly performed aquatic exercise with the
      study endpoint--that is, all-cause death or start of dialysis. Consecutive CKD
      patients were included in the study in January 2002. The exercise group (n=7)
      exercised regularly under the supervision of physiotherapist for 10 years; the
      control group (n=9), matched in terms of age and clinical parameters, remained
      sedentary. Low-intensity aerobic aquatic exercise was performed regularly twice a
      week; 32 weeks or more of exercise therapy sessions were conducted annually. None
      of the members of the aquatic exercise group reached dialysis or died in 10
      years. In the sedentary control group, 55% reached the study endpoint--renal
      replacement therapy (n=2) or all-cause death (n=3). Occurrence of the study
      endpoint, compared using the exact multinomial test with unconditional margins,
      was statistically significantly different (P-value: 0.037) between the study
      groups. Regular supervised aquatic exercise arrested CKD progression. There was a
      statistically significant difference between the sedentary group and the exercise
      group in reaching renal replacement therapy or all-cause death in a follow-up
      time of 10 years.

PMID- 24859429
TI  - Comparative study of the antitumor activity of Nab-paclitaxel and intraperitoneal
      solvent-based paclitaxel regarding peritoneal metastasis in gastric cancer.
AB  - Intraperitoneal (i.p.) chemotherapy with paclitaxel (PTX) has been shown to be a
      promising treatment strategy for peritoneal metastasis. The present study focused
      on the comparative evaluation of the therapeutic efficacy of nanoparticle albumin
      bound PTX (Nab-PTX) and i.p. administration of the conventional solvent-based PTX
      (Sb-PTX). We also investigated the difference in antitumor activity depending on
      the route of administration in the Nab-PTX treatment. Nab-PTX was administered
      i.p. or intravenously (i.v.) and Sb-PTX was administered i.p. at equitoxic and
      equal doses to nude mice bearing gastric cancer OCUM-2MD3 cell subcutaneous and
      peritoneal xenografts. Therapeutic efficacy of Sb-PTX and Nab-PTX was evaluated
      as inhibition of tumor growth using a peritoneal metastatic model with
      subcutaneous xenografts. The survival rate was also investigated using mouse
      peritoneal models. For assessment of subcutaneous tumors, the change in tumor
      volume was measured, and for assessment of peritoneal tumors, the weight of
      ascitic fluid and the total peritoneal tumor burden were measured for each
      individual mouse. At equitoxic doses, treatment with Nab-PTX resulted in a
      greater reduction in the size of subcutaneous tumors and the weight of ascites
      and peritoneal burden as compared with i.p. Sb-PTX (p<0.05). Treatment with i.p.
      and i.v. Nab-PTX also achieved greater survival benefit than i.p. Sb-PTX
      (p<0.05). In contrast, there was no significant difference in the degree of tumor
      reduction and the survival time between both drugs at equal doses. With regard to
      the route of administration, the antitumor efficacy of Nab-PTX after i.v.
      administration was equivalent to the efficacy after i.p. administration. These
      results suggest that i.v. Nab-PTX may be another encouraging treatment option
      that can target peritoneal dissemination in gastric cancer.

PMID- 24859431
TI  - Automated monitoring: a potential solution for achieving sustainable improvement
      in hand hygiene practices.
AB  - Adequate hand hygiene is often considered as the most effective method of
      reducing the rates of hospital-acquired infections, which are one of the major
      causes of increased cost, morbidity, and mortality in healthcare. Electronic
      monitoring technologies provide a promising direction for achieving sustainable
      hand hygiene improvement by introducing the elements of automated feedback and
      creating the possibility to automatically collect individual hand hygiene
      performance data. The results of the multiphase testing of an automated hand
      hygiene reminding and monitoring system installed in a complex continuing care
      setting are presented. The study included a baseline Phase 1, with the system
      performing automated data collection only, a preintervention Phase 2 with hand
      hygiene status indicator enabled, two intervention Phases 3 and 4 with the system
      generating hand hygiene reminding signals and periodic performance feedback
      sessions provided, and a postintervention Phase 5 with only hand hygiene status
      indicator enabled and no feedback sessions provided. A significant increase in
      hand hygiene performance observed during the first intervention Phase 3 was
      sustained over the second intervention Phase 4, with the postintervention phase
      also indicating higher hand hygiene activity rates compared with the
      preintervention and baseline phases. The overall trends observed during the
      multiphase testing, the factors affecting acceptability of the automated hand
      hygiene monitoring system, and various strategies of technology deployment are
      discussed. 

PMID- 24859434
TI  - New trends and affinity tag designs for recombinant protein purification.
AB  - Engineered purification tags can facilitate very efficient purification of
      recombinant proteins, resulting in high yields and purities in a few standard
      steps. Over the years, many different purification tags have been developed,
      including short peptides, epitopes, folded protein domains, non-chromatographic
      tags and more recently, compound multifunctional tags with optimized
      capabilities. Although classic proteases are still primarily used to remove the
      tags from target proteins, new self-cleaving methods are gaining traction as a
      highly convenient alternative. In this review, we discuss some of these emerging
      trends, and examine their potential impacts and remaining challenges in
      recombinant protein research. 

PMID- 24859436
TI  - Have screening harms become newsworthy? News coverage of prostate and colorectal
      cancer screening since the 2008 USPSTF recommendation changes.
AB  - In 2008, the US Preventive Services Task Force updated its recommendations to
      discourage screening for prostate cancer in men over 75 and for colorectal cancer
      in adults over 85. We aimed to determine whether newspapers portrayed these
      screenings differently after these recommendation changes. A quantitative content
      analysis included articles on prostate-specific antigen (PSA) testing or
      colonoscopy in US newspapers from 2005 to 2012. Outcomes included the number of
      benefits and harms mentioned and the gist expert and lay readers might get from
      articles. Benefits in PSA articles (n = 222) and harms and benefits in
      colonoscopy articles (n = 65) did not change over time. Mentions of PSA harms
      increased after 2008 (p < .01). Expected expert gist of PSA articles became more
      negative after 2008 (p < .01). Expected lay gist was positive and did not change.
      News coverage of PSA testing harms increased without a decrease in the discussion
      of benefits. Consumers, especially lay consumers, are receiving unbalanced
      information on cancer screening. 

PMID- 24859437
TI  - Targeted nanoparticles for simultaneous delivery of chemotherapeutic and
      hyperthermia agents--an in vitro study.
AB  - The purpose of this study was to prepare targeted Poly lactide-co-glycolide
      (PLGA) nanoparticles with simultaneous entrapment of indocyanine green (ICG) and
      doxorubicin (DOX) by surface decorating them with tumor specific monoclonal
      antibodies in order to achieve simultaneous therapy and imaging. ICG was chosen
      as an imaging and hyperthermia agent and DOX was used as a chemotherapeutic
      agent. ICG and DOX were incorporated into PLGA nanoparticles using the oil-in
      water emulsion solvent evaporation technique. These nanoparticles were further
      surface decorated with antibodies against Human Epithelial Receptor-2 (HER-2)
      using carbodiimide chemistry. The uptake of antibody conjugated ICG-DOX-PLGA
      nanoparticles (AIDNP) was enhanced in SKOV-3 (HER-2 overexpressing cell lines)
      compared to their non-conjugated counterparts (ICG-DOX-PLGA nanoparticles
      (IDNP)). The uptake of antibody conjugated ICG-DOX-PLGA nanoparticles, however,
      was similar in MES-SA and MES-SA/Dx5 cancer cells (HER-2 negative cell lines),
      which were used as negative controls. The cytotoxicity results after laser
      treatment (808 nm, 6.7 W/cm(2)) showed an enhanced toxicity in treatment of SKOV
      3. The negative controls exhibited comparable cytotoxicity with or without
      exposure to the laser. Thus, this study showed that these antibody conjugated ICG
      DOX-PLGA nanoparticles have potential for combinatorial chemotherapy and
      hyperthermia.

PMID- 24859435
TI  - Diabetes as risk factor for incident coronary heart disease in women compared
      with men: a systematic review and meta-analysis of 64 cohorts including 858,507
      individuals and 28,203 coronary events.
AB  - AIMS/HYPOTHESIS: A previous pooled analysis suggested that women with diabetes
      are at substantially increased risk of fatal CHD compared with affected men.
      Additional findings from several larger and more contemporary studies have since
      been published on the sex-specific associations between diabetes and incident
      CHD. We performed an updated systematic review with meta-analysis to provide the
      most reliable evidence of any sex difference in the effect of diabetes on
      subsequent risk of CHD. METHODS: PubMed MEDLINE was systematically searched for
      prospective population-based cohort studies published between 1 January 1966 and
      13 February 2013. Eligible studies had to have reported sex-specific RR estimates
      for incident CHD associated with diabetes and its associated variability that had
      been adjusted at least for age. Random-effects meta-analyses with inverse
      variance weighting were used to obtain sex-specific RRs and the RR ratio (RRR)
      (women:men) for incident CHD associated with diabetes. RESULTS: Data from 64
      cohorts, including 858,507 individuals and 28,203 incident CHD events, were
      included. The RR for incident CHD associated with diabetes compared with no
      diabetes was 2.82 (95% CI 2.35, 3.38) in women and 2.16 (95% CI 1.82, 2.56) in
      men. The multiple-adjusted RRR for incident CHD was 44% greater in women with
      diabetes than in men with diabetes (RRR 1.44 [95% CI 1.27, 1.63]) with no
      significant heterogeneity between studies (I (2) = 20%).
      CONCLUSIONS/INTERPRETATION: Women with diabetes have more than a 40% greater risk
      of incident CHD compared with men with diabetes. Sex disparities in
      pharmacotherapy are unlikely to explain much of the excess risk in women, but
      future studies are warranted to more clearly elucidate the mechanisms responsible
      for the substantial sex difference in diabetes-related risk of CHD.

PMID- 24859439
TI  - Anticoagulation and antiplatelet therapy in urological practice: ICUD/AUA review
      paper.
AB  - PURPOSE: Given the lack of urology specific directives for the periprocedural
      management of anticoagulant and antiplatelet medications, the AUA (American
      Urological Association) and ICUD (International Consultation on Urological
      Disease) named an international multidisciplinary panel to develop consensus
      based recommendations. MATERIALS AND METHODS: A systematic literature review was
      queried by a methodologist for 3 questions. 1) When and in whom can
      anticoagulant/antiplatelet prophylaxis be stopped in preparation for surgery? 2)
      What procedures can be safely performed without discontinuing
      anticoagulant/antiplatelet prophylaxis? 3) What periprocedural strategies can
      adequately balance the risk of major surgical bleeding vs the risk of major
      thrombotic event? Hematology and cardiology guidelines, and 79 articles were
      selected for full review. RESULTS: Multidisciplinary management of
      anticoagulant/antiplatelet medications for patients with recent thromboembolic
      events, mechanical cardiac valves, atrial fibrillation and cardiac stents would
      reduce the high morbidity and mortality of inexpertly discontinuing or modifying
      these lifesaving therapies. No elective procedures requiring interruption of dual
      antiplatelet therapies should be performed with a recent bare metal or drug
      eluting stent. The risk of significant bleeding complications is low for patients
      who require continuation of aspirin for ureteroscopy, transrectal prostate
      biopsies, laser prostate outlet procedures and percutaneous renal biopsy. Open
      extirpative prostate and renal procedures can be performed with a low risk of
      significant hemorrhage for patients on aspirin and those requiring heparin based
      bridging strategies. The current literature does not give direction on the timing
      of the resumption of anticoagulant/antiplatelet prophylaxis other than that it be
      resumed as soon as the risk of bleeding has decreased. CONCLUSIONS: A total of
      2,674 nonredundant article abstracts were obtained and assessed for relevance to
      key questions outlined by the panel. Overall 106 articles were selected for full
      text review and accepted or rejected based on the relation to the topic, quality
      of information and key questions. A total of 79 articles were accepted. Reasons
      for rejection (27 articles) included abstract only (12), insufficient information
      or unrelated to topic (13) and redundancy (2). We extracted study design, patient
      population, followup period and results from accepted articles, which serve as
      the evidence base.

PMID- 24859438
TI  - Microbial characterization of microbial ecosystems associated to evaporites domes
      of gypsum in Salar de Llamara in Atacama desert.
AB  - The Central Andes in northern Chile contains a large number of closed basins
      whose central depression is occupied by saline lakes and salt crusts (salars).
      One of these basins is Salar de Llamara (850 m a.s.l.), where large domed
      structures of seemingly evaporitic origin forming domes can be found. In this
      work, we performed a detailed microbial characterization of these domes.
      Mineralogical studies revealed gypsum (CaSO(4)) as a major component. Microbial
      communities associated to these structures were analysed by 454 16S rDNA amplicon
      sequencing and compared between winter and summer seasons. Bacteroidetes
      Proteobacteria and Planctomycetes remained as the main phylogenetic groups, an
      increased diversity was found in winter. Comparison of the upper air-exposed part
      and the lower water-submerged part of the domes in both seasons showed little
      variation in the upper zone, showing a predominance of Chromatiales
      (Gammaproteobacteria), Rhodospirillales (Alphaproteobacteria), and
      Sphingobacteriales (Bacteroidetes). However, the submerged part showed marked
      differences between seasons, being dominated by Proteobacteria (Alpha and Gamma)
      and Verrucomicrobia in summer, but with more diverse phyla found in winter. Even
      though not abundant by sequence, Cyanobacteria were visually identified by
      scanning electron microscopy (SEM), which also revealed the presence of diatoms.
      Photosynthetic pigments were detected by high-performance liquid chromatography,
      being more diverse on the upper photosynthetic layer. Finally, the system was
      compared with other endoevaporite, mats microbialite and Stromatolites microbial
      ecosystems, showing higher similitude with evaporitic ecosystems from Atacama and
      Guerrero Negro. This environment is of special interest for extremophile studies
      because microbial life develops associated to minerals in the driest desert all
      over the world. Nevertheless, it is endangered by mining activity associated to
      copper and lithium extraction; thus, its environmental protection preservation is
      strongly encouraged.

PMID- 24859440
TI  - Prospective trial of the detection of urolithiasis on ultralow dose (sub mSv)
      noncontrast computerized tomography: direct comparison against routine low dose
      reference standard.
AB  - PURPOSE: In this prospective trial we compared ultralow dose computerized
      tomography reconstruction algorithms and routine low dose computerized tomography
      for detecting urolithiasis. MATERIALS AND METHODS: A total of 48 consenting
      adults prospectively underwent routine low dose noncontrast computerized
      tomography immediately followed by an ultralow dose series targeted at a 70% to
      90% reduction from the routine low dose technique (sub mSv range). Ultralow dose
      series were reconstructed with filtered back projection, and adaptive statistical
      and model based iterative reconstruction techniques. Transverse (axial) and
      coronal images were sequentially reviewed by 3 relatively inexperienced trainees,
      including a radiology resident, a urology fellow and an abdominal imaging fellow.
      Three experienced abdominal radiologists independently reviewed the routine low
      dose filtered back projection images, which served as the reference standard.
      RESULTS: The mean effective dose for the ultralow dose scans was 0.91 mSv (median
      0.82), representing a mean +/- SD 78% +/- 5% decrease compared to the routine low
      dose. Overall sensitivity and positive predictive value per stone for ultralow
      dose computerized tomography at a 4 mm threshold was 0.91 and 0.98, respectively.
      Sensitivity, specificity, positive and negative predictive values, and accuracy
      per patient were 0.87, 1.00, 1.00, 0.94 and 0.96, respectively. At a 4 mm
      threshold the sensitivity and positive predictive value per stone of the ultralow
      dose series for filtered back projection, and adaptive statistical and model
      based iterative reconstruction was 0.89 and 0.96, 0.91 and 0.98, and 0.93 and
      1.00, respectively. Sensitivity, specificity, positive and negative predictive
      values, and accuracy per patient at the 4 mm threshold were 0.82, 1.00, 1.00,
      0.91 and 0.94 for filtered back projection, 0.85, 1.00, 1.00, 0.93 and 0.95 for
      adaptive statistical iterative reconstruction, and 0.94, 1.00, 1.00, 0.97 and
      0.98 for model based iterative reconstruction, respectively. Sequential review of
      coronal images changed the final stone reading in 13% of cases and improved
      diagnostic confidence in 49%. CONCLUSIONS: At a 4 mm renal calculus size
      threshold ultralow dose computerized tomography is accurate for detection when
      referenced against routine low dose series with dose reduction to below the level
      of a typical 2-view plain x-ray of the kidneys, ureters and bladder. Slight
      differences were seen among the reconstruction algorithms. There was mild
      improvement with model based iterative reconstruction over filtered back
      projection and adaptive statistical iterative reconstruction. Coronal images
      improved detection and diagnostic confidence over axial images alone.

PMID- 24859443
TI  - Elevated serum IgE may be associated with development of ketamine cystitis.
AB  - PURPOSE: Previous studies revealed bladder mast cell and eosinophil cell
      infiltration in patients with ketamine cystitis. Due to possible hypersensitivity
      in those with this condition we investigated the association of serum Ig,
      histology findings and symptoms in patients with ketamine cystitis. MATERIALS AND
      METHODS: We evaluated patients with ketamine cystitis for maximal bladder
      capacity, serum IgE, IgG and IgM, and pain visual analog scale score. Bladder
      biopsies were assessed for mast cells and eosinophils. Patients with interstitial
      cystitis/bladder pain syndrome, acute bacterial cystitis and controls were also
      studied. We used the Mann-Whitney U test for nonparametric data to compare serum
      IgE among groups with p <0.017 considered significant. RESULTS: Median serum IgE
      was significantly higher in the 20 patients with ketamine cystitis (205.5 IU/ml,
      IQR 36.9, 514.0) than in the 10 controls (33.4 IU/ml, IQR 13.5, 71.7, p = 0.015)
      and the 15 with acute bacterial cystitis (34.6 IU/ml, IQR 24.2, 101.9, p =
      0.015). It was marginally higher than in the 13 patients with interstitial
      cystitis/bladder pain syndrome (65.8 IU/ml, IQR 11.9, 133.0, p = 0.029). Of
      patients with ketamine cystitis the median visual analog scale pain score was
      significantly higher in those with serum IgE greater than compared to less than
      200 IU/ml. Maximal bladder capacity was significantly less in patients with
      ketamine cystitis who had higher IgE. Patients with severe or moderate bladder
      eosinophil infiltration had a greater visual analog scale score, higher serum IgE
      and smaller maximal bladder capacity than patients with no or mild eosinophil
      infiltration. Serum IgE and the visual analog scale score correlated
      significantly (r(2) = 0.318, p = 0.01). CONCLUSIONS: Patients with ketamine
      cystitis had higher serum IgE than patients with interstitial cystitis/bladder
      pain syndrome or acute bacterial cystitis, or controls. Serum IgE and the
      severity of eosinophil infiltration were associated with bladder pain severity
      and small maximal bladder capacity.

PMID- 24859441
TI  - Low detectable prostate specific antigen after radical prostatectomy--treat or
      watch?
AB  - PURPOSE: We determined whether the pattern of low detectable prostate specific
      antigen during the first 3 years of followup after radical prostatectomy would
      predict subsequent biochemical recurrence. MATERIALS AND METHODS: An
      institutional database was queried to identify 1,136 patients who underwent open
      retropubic or robot-assisted radical prostatectomy between January 5, 1993 and
      December 29, 2008. After applying exclusion criteria we used serum prostate
      specific antigen and the prostate specific antigen pattern during the first 3
      years of followup to divide 566 men into 3 groups, including 1) undetectable
      prostate specific antigen (0.03 ng/ml or less), 2) low detectable-stable prostate
      specific antigen (greater than 0.03 and less than 0.2 ng/ml, no 2 subsequent
      increases and/or prostate specific antigen velocity less than 0.05 ng per year)
      and 3) low detectable-unstable prostate specific antigen (greater than 0.03 and
      less than 0.2 ng/ml, 2 subsequent increases according to NCCN criteria and/or
      prostate specific antigen velocity 0.05 ng per year or greater). The primary end
      point was biochemical recurrence, defined as prostate specific antigen 0.2 ng/ml
      or greater, or receipt of radiation therapy beyond 3 years of followup. RESULTS:
      Seven-year biochemical recurrence-free survival was 95%, 94% and 37% in the
      undetectable, low detectable-stable and low detectable-unstable groups,
      respectively (log rank test p <0.0001). On multivariate analysis the prostate
      specific antigen pattern during 3 years postoperatively (undetectable vs low
      detectable-unstable HR 15.9 and vs low detectable-stable HR 1.6), pathological T
      stage (pT2 vs greater than pT2 HR 1.8), pathological Gleason score (less than 7
      vs 7 HR 2.3 and less than 7 vs 8-10 HR 3.3) and surgical margins (negative vs
      positive HR 1.8) significantly predicted biochemical recurrence. CONCLUSIONS: The
      combination of prostate specific antigen velocity and NCCN criteria for
      biochemical recurrence separated well men with low detectable prostate specific
      antigen after radical prostatectomy into those who required treatment and those
      who could be safely watched.

PMID- 24859444
TI  - The evolution of urethroplasty for bulbar urethral stricture disease: lessons
      learned from a single center experience.
AB  - PURPOSE: We reviewed the evolution of repairs for bulbar urethral stricture
      disease and analyzed changes in outcomes. MATERIALS AND METHODS: We
      retrospectively reviewed the records of 429 men who underwent urethroplasty for
      bulbar urethral stricture disease from January 1996 to September 2011. Patient
      demographics, stricture related details, and intraoperative and postoperative
      information were collected. We used 1-way ANOVA for differences in age and
      stricture length, the Fisher exact test for differences in recurrence rates, and
      the t-test and chi-square test with the Bonferroni correction for subgroup
      analysis. RESULTS: Of the 429 men 384 (90%) had followup data available. Buccal
      mucosa surpassed penile skin as our preferred tissue for augmented anastomotic
      repairs by 1999. It was accompanied by an improved recurrence rate (21.6% vs
      5.8%, p = 0.002). The average length of strictures treated with excision and
      primary anastomosis increased after 2004 (1.29 vs 1.54 cm, p = 0.05) but this was
      not associated with a significant change in the recurrence rate (3.0% vs 6.9%, p
      = 0.27). CONCLUSIONS: The transition from penile skin to buccal mucosa for
      augmented anastomotic repair was relatively abrupt. We have become more
      aggressive when performing excision and primary anastomosis with respect to
      stricture length. These changes resulted in improved outcomes. Continuing review
      of our practices, awareness of results reported by others and intuition
      contributed to our changes but prospective analysis will be the best way to
      continually improve outcomes.

PMID- 24859442
TI  - Prospective external validation of a bladder cancer detection model.
AB  - PURPOSE: Few studies have combined clinical prognostic factors with urinary
      biomarkers into risk profiles that can be used to predict the likelihood of
      bladder cancer. We previously developed and internally validated a bladder cancer
      detection nomogram that combines clinical features with the NMP22(r)
      BladderChek(r) test. To consider extensive use of the model the nomogram was
      tested in a prospective cohort of patients who presented with hematuria.
      MATERIALS AND METHODS: Patients referred for hematuria evaluation were
      prospectively enrolled at 3 centers. Each patient underwent complete urological
      evaluation, including history, examination, cystoscopy, cytology and NMP22. A
      logistic regression model to predict urothelial bladder carcinoma was also
      developed to compare the performance of clinical data with and without adding
      NMP22 and urinary cytology. RESULTS: The study included 381 patients (50.7%
      women) with a median age of 58 years. Urothelial bladder carcinoma was detected
      in 23 patients (6%). It was associated with age greater than 65 (11.1% vs 4% of
      patients, p = 0.012), male gender (10.1% vs 2%, p = 0.003), white ethnicity (9.2%
      vs 3.1%, p = 0.016), gross hematuria (9.9% vs 2.5%, p = 0.005), positive NMP22
      (37% vs 3.7%, p <0.001) and positive cytology (83.3% vs 3.9%, p <0.001).
      Predictive accuracy of the bladder cancer detection nomogram was 80.2%. The
      calibration plot indicated that the previously published nomogram was well
      calibrated in patients with a less than 15% predicted probability of urothelial
      bladder carcinoma. CONCLUSIONS: We prospectively validated a highly accurate tool
      that combines clinical factors and a urinary biomarker to detect bladder cancer.
      This tool can help prioritize urological referrals for patients with hematuria.

PMID- 24859445
TI  - Dietary intake of fiber, fruit and vegetables decreases the risk of incident
      kidney stones in women: a Women's Health Initiative report.
AB  - PURPOSE: We evaluated the relationship between dietary fiber, fruit and vegetable
      intake, and the risk of kidney stone formation. MATERIALS AND METHODS: Overall
      83,922 postmenopausal women from the Women's Health Initiative observational
      study were included in the analysis and followed prospectively. Cox proportional
      hazards regression analyses were used to evaluate the associations between total
      dietary fiber, fruit and vegetable intake, and the risk of incident kidney stone
      formation, adjusting for nephrolithiasis risk factors (age, race/ethnicity,
      geographic region, diabetes mellitus, calcium supplementation, hormone therapy
      use, body mass index and calibrated caloric intake; and dietary water, sodium,
      animal protein and calcium intake). Women with a history of kidney stones (3,471)
      were analyzed separately. RESULTS: Mean age of the women was 64+/-7 years, 85%
      were white and 2,937 (3.5%) experienced a kidney stone in a median followup of 8
      years. In women with no history of kidney stones higher total dietary fiber (6%
      to 26% decreased risk, p <0.001), greater fruit intake (12% to 25% decreased
      risk, p <0.001) and greater vegetable intake (9% to 22% decreased risk, p=0.002)
      were associated with a decreased risk of incident kidney stone formation in
      separate adjusted models. In women with a history of stones there were no
      significant protective effects of fiber, fruit or vegetable intake on the risk of
      kidney stone recurrence. CONCLUSIONS: Greater dietary intake of fiber, fruits and
      vegetables was associated with a reduced risk of incident kidney stones in
      postmenopausal women. The protective effects were independent of other known risk
      factors for kidney stones. In contrast, there was no reduction in risk in women
      with a history of stones.

PMID- 24859447
TI  - Theoretical studies on a new high energy density compound 6-amino-7
      nitropyrazino[2,3-e][1,2,3,4]tetrazine 1,3,5-trioxide (ANPTTO).
AB  - The derivatives of 1,2,3,4-tetrazine may be promising candidates for high-energy
      density compounds and are receiving more and more attentions. In this study, a
      new derivative 6-amino-7-nitropyrazino[2,3-e][1,2,3,4]tetrazine 1,3,5-trioxide
      (ANPTTO) has been designed. The geometrical structure and IR spectrum in the gas
      phase were studied at the B3LYP/6-31G* level of density functional theory (DFT).
      The crystal structure was predicted by molecular mechanics method and refined by
      the GGA/BOP function of periodic DFT with the basis set of TNP. The gas phase
      enthalpy of formation was calculated by the homodesmotic reaction method. The
      enthalpy of sublimation and solid phase enthalpy of formation were also
      predicted. The detonation properties were estimated with the Kamlet-Jacobs
      equations based on the predicted density and enthalpy of formation in solid
      state. The available free space in the lattice and resonance energy were
      calculated to evaluate its stability. ANPTTO has a high stability and is a
      promising high energetic component with the density >2 g . cm(-3), detonation
      velocity >9000 m . s(-1), and detonation pressure >40 GPa. A synthetic route was
      proposed to provide a consideration for further study. 

PMID- 24859448
TI  - NMR and quantum chemical analysis of 3-(2-methly-2-phenylhydrazinyl)cyclohex-2-en
      1-one.
AB  - Two-dimensional representation of a molecular structure is in some cases
      misleading, since it may not correctly represent important details and may not
      provide adequate information on the electronic structure of the molecule. In such
      cases the physical-chemical properties of the molecule will not be properly
      interpreted on the basis of the molecular formula. For example, the NMR spectrum
      will differ significantly from what would be intuitively expected on the basis of
      this formula and one can deduce the correct electronic and steric structure of
      the molecule from the obtained spectra instead. In this article the NMR and
      quantum chemical analysis of the title compound 3-(2-methly-2
      phenylhydrazinyl)cyclohex-2-en-1-one will be presented. The unusual NMR spectra
      and surprising protonation site of this compound will be explained based on the
      delocalization of the pi-symmetric orbitals of its molecules. The proposed
      electronic structure and the observed but unexpected physical-chemical properties
      have been confirmed by quantum chemical calculations. 

PMID- 24859449
TI  - Rhbdd3 controls autoimmunity by suppressing the production of IL-6 by dendritic
      cells via K27-linked ubiquitination of the regulator NEMO.
AB  - Excessive activation of dendritic cells (DCs) leads to the development of
      autoimmune and inflammatory diseases, which has prompted a search for regulators
      of DC activation. Here we report that Rhbdd3, a member of the rhomboid family of
      proteases, suppressed the activation of DCs and production of interleukin 6 (IL
      6) triggered by Toll-like receptors (TLRs). Rhbdd3-deficient mice spontaneously
      developed autoimmune diseases characterized by an increased abundance of the TH17
      subset of helper T cells and decreased number of regulatory T cells due to the
      increase in IL-6 from DCs. Rhbdd3 directly bound to Lys27 (K27)-linked
      polyubiquitin chains on Lys302 of the modulator NEMO (IKKgamma) via the ubiquitin
      binding-association (UBA) domain in endosomes. Rhbdd3 further recruited the
      deubiquitinase A20 via K27-linked polyubiquitin chains on Lys268 to inhibit K63
      linked polyubiquitination of NEMO and thus suppressed activation of the
      transcription factor NF-kappaB in DCs. Our data identify Rhbdd3 as a critical
      regulator of DC activation and indicate K27-linked polyubiquitination is a potent
      ubiquitin-linked pattern involved in the control of autoimmunity.

PMID- 24859450
TI  - The transcription factor Foxp1 is a critical negative regulator of the
      differentiation of follicular helper T cells.
AB  - CD4(+) follicular helper T cells (T(FH) cells) are essential for germinal center
      (GC) responses and long-lived antibody responses. Here we report that naive
      CD4(+) T cells deficient in the transcription factor Foxp1 'preferentially'
      differentiated into T(FH) cells, which resulted in substantially enhanced GC and
      antibody responses. We found that Foxp1 used both constitutive Foxp1A and Foxp1D
      induced by stimulation of the T cell antigen receptor (TCR) to inhibit the
      generation of T(FH) cells. Mechanistically, Foxp1 directly and negatively
      regulated interleukin 21 (IL-21); Foxp1 also dampened expression of the
      costimulatory molecule ICOS and its downstream signaling at early stages of T
      cell activation, which rendered Foxp1-deficient CD4(+) T cells partially
      resistant to blockade of the ICOS ligand (ICOSL) during T(FH) cell development.
      Our findings demonstrate that Foxp1 is a critical negative regulator of T(FH)
      cell differentiation.

PMID- 24859451
TI  - The E3 ubiquitin ligase Itch is required for the differentiation of follicular
      helper T cells.
AB  - Follicular helper T cells (T(FH) cells) are responsible for effective B cell
      mediated immunity, and Bcl-6 is a central factor for the differentiation of T(FH)
      cells. However, the molecular mechanisms that regulate the induction of T(FH)
      cells remain unclear. Here we found that the E3 ubiquitin ligase Itch was
      essential for the differentiation of T(FH) cells, germinal center responses and
      immunoglobulin G (IgG) responses to acute viral infection. Itch acted
      intrinsically in CD4(+) T cells at early stages of T(FH) cell development. Itch
      seemed to act upstream of Bcl-6 expression, as Bcl-6 expression was substantially
      impaired in Itch(-/-) cells, and the differentiation of Itch(-/-) T cells into
      T(FH) cells was restored by enforced expression of Bcl-6. Itch associated with
      the transcription factor Foxo1 and promoted its ubiquitination and degradation.
      The defective T(FH) differentiation of Itch(-/-) T cells was rectified by
      deletion of Foxo1. Thus, our results indicate that Itch acts as an essential
      positive regulator in the differentiation of T(FH) cells.

PMID- 24859452
TI  - Glial cells in amyotrophic lateral sclerosis.
AB  - For more than twenty years glial cells have been implicated in the pathogenetic
      cascades for genetic and sporadic forms of ALS. The biological role of glia,
      including the principal CNS glia, astroglia and oligodendroglia, as well as the
      myeloid derived microglia, has uniformly led to converging data sets that
      implicate these diverse cells in the degeneration of neurons in ALS. Originating
      as studies in postmortem human brain implicating astroglia, the research
      progressed to strongly implicate microglia and contributors to CNS injury in all
      forms of ALS. Most recently and unexpectedly, oligodendroglia have also been
      shown in animal model systems and human brain to play an early role in the
      dysfunction and death of ALS neurons. These studies have identified a number of
      diverse cellular cascades that could be, or have already been, the target of
      therapeutic interventions. Understanding the temporal and regional role of these
      cells and the magnitude of their contribution will be important for future
      interventions. Employing markers of these cell types may also allow for future
      important patient subgrouping and pharmacodynamic drug development tools. 

PMID- 24859454
TI  - Rapamycin and everolimus facilitate hepatitis E virus replication: revealing a
      basal defense mechanism of PI3K-PKB-mTOR pathway.
AB  - BACKGROUND & AIMS: Humans are frequently exposed to hepatitis E virus (HEV).
      Nevertheless, the disease mainly affects pregnant women and immunocompromised
      individuals. Organ recipients receiving immunosuppressants, such as rapalogs, to
      prevent rejection have a high risk for developing chronic hepatitis following HEV
      infection. Rapalogs constitute potent inhibitors of mTOR including rapamycin and
      everolimus. As a master kinase, the mechanism-of-action of mTOR is not only
      associated with the immunosuppressive capacity of rapalogs but is also tightly
      regulated during pregnancy because of increased nutritional demands. METHODS: We
      thus investigated the role of mTOR in HEV infection by using two state-of-the-art
      cell culture models: a subgenomic HEV containing luciferase reporter and a full
      length HEV infectious cell culture system. RESULTS: In both subgenomic and full
      length HEV models, HEV infection was aggressively escalated by treatment of
      rapamycin or everolimus. Inhibition of mTOR was confirmed by Western blot showing
      the inhibition of its downstream target, S6 phosphorylation. Consistently, stable
      silencing of mTOR by lentiviral RNAi resulted in a significant increase in
      intracellular HEV RNA, suggesting an antiviral function of mTOR in HEV infection.
      By targeting a series of other up- and downstream elements of mTOR signaling, we
      further revealed an effective basal defense mechanism of the PI3K-PKB-mTOR
      pathway against HEV, which is through the phosphorylated eIF4E-binding protein 1
      (4E-BP1), however independent of autophagy formation. CONCLUSIONS: The discovery
      that PI3K-PKB-mTOR pathway limits HEV infection through 4E-BP1 and acts as a gate
      keeper in human HEV target cells bears significant implications in managing
      immunosuppression in HEV-infected organ transplantation recipients.

PMID- 24859456
TI  - TERT promoter mutations: gatekeeper and driver of hepatocellular carcinoma.

PMID- 24859453
TI  - Inhibition of heat shock protein 90 alleviates steatosis and macrophage
      activation in murine alcoholic liver injury.
AB  - BACKGROUND & AIMS: Heat shock protein 90 (hsp90) is an emerging therapeutic
      target in chronic liver diseases. Hsp90 plays an important role in liver immune
      cell activation; however its role in alcoholic liver disease (ALD) remains
      elusive. Here we hypothesize that hsp90 is crucial in alcohol induced steatosis
      and pro-inflammatory cytokine production. To test this hypothesis, we employed a
      pharmacological inhibitor of hsp90, 17-DMAG (17-Dimethylamino-ethylamino-17
      demethoxygeldanamycin) in an in vivo mouse model of acute and chronic alcoholic
      liver injury. METHODS: C57BL/6 mice were given either a single dose of ethanol
      via oral gavage (acute) or chronically fed alcohol for 2 weeks followed by oral
      gavage (chronic-binge). 17-DMAG was administered during or at the end of feeding.
      Liver injury parameters, inflammatory cytokines and lipid metabolism genes were
      analysed. RESULTS: Our results reveal increased expression of hsp90 in human and
      mouse alcoholic livers. In vivo inhibition of hsp90, using 17-DMAG, not only
      prevented but also alleviated alcoholic liver injury, determined by lower serum
      ALT, AST and reduced hepatic triglycerides. Mechanistic analysis showed that 17
      DMAG decreased alcohol mediated oxidative stress, reduced serum endotoxin,
      decreased inflammatory cells, and diminished sensitization of liver macrophages
      to LPS, resulting in downregulation of CD14, NFkappaB inhibition, and decreased
      pro-inflammatory cytokine production. Hsp90 inhibition decreased fatty acid
      synthesis genes via reduced nuclear SREBP-1 and favoured fatty acid oxidation
      genes via PPARalpha. CONCLUSIONS: Inhibition of hsp90 decreased alcohol induced
      steatosis and pro-inflammatory cytokines and inhibited alcoholic liver injury.
      Hsp90 is therefore relevant in human alcoholic cirrhosis and a promising
      therapeutic target in ALD.

PMID- 24859455
TI  - Identification of prognostic biomarkers in hepatitis B virus-related
      hepatocellular carcinoma and stratification by integrative multi-omics analysis.
AB  - BACKGROUND & AIMS: The differentiation of distinct multifocal hepatocellular
      carcinoma (HCC): multicentric disease vs. intrahepatic metastases, in which the
      management and prognosis varies substantively, remains problematic. We aim to
      stratify multifocal HCC and identify novel diagnostic and prognostic biomarkers
      by performing whole genome and transcriptome sequencing, as part of a multi-omics
      strategy. METHODS: A complete collection of tumour and somatic specimens
      (intrahepatic HCC lesions, matched non-cancerous liver tissue and blood) were
      obtained from representative patients with multifocal HCC exhibiting two distinct
      postsurgical courses. Whole-genome and transcriptome sequencing with genotyping
      were performed for each tissue specimen to contrast genomic alterations,
      including hepatitis B virus integrations, somatic mutations, copy number
      variations, and structural variations. We then constructed a phylogenetic tree to
      visualise individual tumour evolution and performed functional enrichment
      analyses on select differentially expressed genes to elucidate biological
      processes involved in multifocal HCC development. Multi-omics data were
      integrated with detailed clinicopathological information to identify HCC
      biomarkers, which were further validated using a large cohort of HCC patients (n
      = 174). RESULTS: The multi-omics profiling and tumour biomarkers could
      successfully distinguish the two multifocal HCC types, while accurately
      predicting clonality and aggressiveness. The dual-specificity protein kinase TTK,
      which is a key mitotic checkpoint regulator with links to p53 signaling, was
      further shown to be a promising overall prognostic marker for HCC in the large
      patient cohort. CONCLUSIONS: Comprehensive multi-omics characterisation of
      multifocal tumour evolution may improve clinical decision-making, facilitate
      personalised medicine, and expedite identification of novel biomarkers and
      therapeutic targets in HCC.

PMID- 24859457
TI  - Repressive histone methylation: a case study in deterministic versus stochastic
      gene regulation.
AB  - Transcriptionally repressive histone lysine methylation is used by eukaryotes to
      tightly control cell fate. Here we explore the importance of this form of
      regulation in the control of clustered genes in the genome. Two distinctly
      regulated gene families with important roles in vertebrates are discussed, namely
      the Hox genes and olfactory receptor genes. Major recent advances in these two
      fields are compared and contrasted, with an emphasis on the roles of the two
      different forms of histone trimethylation. We discuss how this repression may
      impact both the transcriptional output of these loci and the way higher-order
      chromatin organization is related to their unique control.

PMID- 24859459
TI  - Hunting for Darwin's gemmules and Lamarck's fluid: transgenerational signaling
      and histone methylation.
AB  - Recent studies have discovered phenotypes induced by a transient treatment or
      mutation that persist for multiple generations without mutations in DNA. Both
      invertebrates and vertebrates exhibit such inheritance, and a range of
      environmental factors can act as a trigger. Now referred to as transgenerational
      epigenetic inheritance or TEI, this emerging field faces a big challenge-what
      molecular mechanisms account for inheritance of TEI phenotypes? This review
      describes examples of TEI and focuses on the possible role of histone methylation
      and small RNAs in mediating TEI.

PMID- 24859461
TI  - Short- and long-term biomechanical and morphological study of new suture types in
      abdominal wall closure.
AB  - To perform an abdominal-wall closure, a continuous suture is the preferred
      method. The suture materials that are most commonly employed in abdominal surgery
      are polypropylene and polydioxanone. However, in recent times, new products have
      been marketed, such as non-absorbable polyurethane with elastic properties
      (Assuplus((r)), Assut Europe, Italy) and absorbable barbed polydioxanone
      (Filbloc((r)), Assut Europe, Italy). The purpose of this study was to compare the
      ability of those against the standard polypropylene (Surgipro(TM), Covidien, USA)
      and polydioxanone (Assufil((r)), Assut Europe, Italy) to mimic the biomechanical
      behavior of the abdominal wall closure. Comparison of the sutures was made first
      with the materials alone and later in a laparotomy closure of a rabbit abdomen,
      used as an animal model. The biomechanical analysis consisted of uniaxial tensile
      tests of threads and sutured samples of the animal abdomen. In the latter case,
      results were analyzed at short- (21days) and long- (180days) term intervals after
      the surgery. The morphology studies and collagen expression of the samples were
      also investigated. The results determined that polydioxanone and polypropylene
      sutures showed a linear elastic behavior, with barbed polydioxanone as the most
      compliant suture and polyurethane as the stiffest. The sutured samples showed a
      statistically significant loss of resistance, measured as the load needed to
      perform a certain stretch, when compared with the corresponding control tissue.
      Analysis of the stress-stretch curves showed that elastic polyurethane was the
      only suture able to reproduce the mechanical behavior of healthy tissue in the
      short term, while the rest of the sutures remained less stiff. This coincides
      with the expression of type I collagen observed in this group at this point in
      the study. In the long term, there was no difference among the sutures, and none
      was able to mimic control behavior. 

PMID- 24859458
TI  - Targeting histone lysine demethylases - progress, challenges, and the future.
AB  - N-Methylation of lysine and arginine residues has emerged as a major mechanism of
      transcriptional regulation in eukaryotes. In humans, N(epsilon)-methyllysine
      residue demethylation is catalysed by two distinct subfamilies of demethylases
      (KDMs), the flavin-dependent KDM1 subfamily and the 2-oxoglutarate- (2OG)
      dependent JmjC subfamily, which both employ oxidative mechanisms. Modulation of
      histone methylation status is proposed to be important in epigenetic regulation
      and has substantial medicinal potential for the treatment of diseases including
      cancer and genetic disorders. This article provides an introduction to the
      enzymology of the KDMs and the therapeutic possibilities and challenges
      associated with targeting them, followed by a review of reported KDM inhibitors
      and their mechanisms of action from kinetic and structural perspectives.

PMID- 24859462
TI  - In vitro fracture resistance of molar teeth restored with a short fibre
      reinforced composite material.
AB  - OBJECTIVES: The purpose of this in vitro study was to evaluate the efficiency of
      a short fibre-reinforced composite (SFRC) material compared to conventional
      composites when restoring class II. MOD cavities in molar teeth with different
      layering techniques. METHODS: One hundred and thirty mandibular third molars were
      divided into 5 groups (n=26). Except for the control group (intact teeth), in all
      other groups MOD cavities were prepared. The cavities were restored by either
      conventional composite with horizontal and oblique layering or by SFRC with
      horizontal and oblique layering. The specimens were submitted to static fracture
      toughness test. Fracture thresholds and fracture patterns were evaluated.
      RESULTS: In general, no statistically significant difference was found in
      fracture toughness between the study groups, except for horizontally layered
      conventional composite restorations, which turned out to be significantly weaker
      than controls. However, SFRC yielded noticeably higher fracture thresholds and
      only obliquely applied SFRC restorations exhibited favourable fracture patterns
      above chance level. CONCLUSIONS: The application of SFRC did not lead to a
      statistically significant improvement of the fracture toughness of molar teeth
      with MOD cavities. Still, SFRC applied in oblique increments measurably reduces
      the chance of unrestorable fractures of molar teeth with class II MOD cavities.
      CLINICAL SIGNIFICANCE: The restoration of severely weakened molar teeth with the
      use of SFRC combined with composite might have advantages over conventional
      composites alone. It was observed from the statistical data, that the application
      of SFRC with an oblique layering technique yielded not significantly but better
      fracture thresholds and more favourable fracture patterns than any other studied
      material/technique combination. Thus further investigations need to be carried
      out, to investigate the possible positive mechanical effects of SFRC. The
      application of the horizontal layering technique with conventional composite
      materials is inferior to the oblique technique and SFRC materials.

PMID- 24859464
TI  - Francois le "commandeur".

PMID- 24859463
TI  - Bone mineralization in children with Wilson's disease.
AB  - BACKGROUND: The goal of this study was to determine bone mineralization in
      children with Wilson's disease (WD). METHODS: Twenty-seven patients (16 males)
      and two age- and gender-matched healthy children for each patient were enrolled
      in the study. Bone mineral content (BMC, grams) and density (BMD, g/cm(2)) at
      lumbar 1-4 vertebrae were measured by dual-energy X-ray absorptiometry. Urinary
      calcium excretion was calculated in 19 patients. The effect of cirrhosis and
      hypercalciuria on BMC and BMD was also evaluated in WD patients. RESULTS: There
      was no statistically significant difference between patients and healthy controls
      regarding mean BMC (33.0 +/- 13.9 vs. 35.8 +/- 13.8 g) (p = 0.940) and mean BMD
      values (0.66 +/- 0.16 vs. 0.71 +/- 0.18 g/cm(2)) (p = 0.269), respectively. Nine
      (47.4 %) patients had hypercalciuria. Hypercalciuric patients had statistically
      significant lower BMC and BMD values than those without hypercalciuria. A
      significant difference continued to be present after age, weight, height, and
      pubertal stage adjustment was done, but disappeared after weight, height, follow
      up duration, and pubertal stage adjustment was done. The presence of cirrhosis
      did not affect BMC and BMD significantly in WD patients. CONCLUSIONS: BMC and BMD
      in children with WD were normal. The presence of hypercalciuria but not cirrhosis
      may affect BMC and BMD negatively in the patients.

PMID- 24859460
TI  - Histone methylation and aging: lessons learned from model systems.
AB  - Aging induces myriad cellular and, ultimately, physiological changes that cause a
      decline in an organism's functional capabilities. Although the aging process and
      the pathways that regulate it have been extensively studied, only in the last
      decade have we begun to appreciate that dynamic histone methylation may
      contribute to this process. In this review, we discuss recent work implicating
      histone methylation in aging. Loss of certain histone methyltransferases and
      demethylases changes lifespan in invertebrates, and alterations in histone
      methylation in aged organisms regulate lifespan and aging phenotypes, including
      oxidative stress-induced hormesis in yeast, insulin signaling in Caenorhabiditis
      elegans and mammals, and the senescence-associated secretory phenotype in
      mammals. In all cases where histone methylation has been shown to impact aging
      and aging phenotypes, it does so by regulating transcription, suggesting that
      this is a major mechanism of its action in this context. Histone methylation
      additionally regulates or is regulated by other cellular pathways that contribute
      to or combat aging. Given the numerous processes that regulate aging and histone
      methylation, and are in turn regulated by them, the role of histone methylation
      in aging is almost certainly underappreciated.

PMID- 24859465
TI  - Cervicitis of unknown etiology.
AB  - Cervicitis has been described by some as the female counterpart of urethritis in
      men. Over the years a number of clinical and microscopy-based definitions have
      been suggested in the literature. Clinical manifestations include mucopurulent
      discharge from the cervix, cervical friability (easy bleeding from the cervix
      with passage of a swab) and cervical ectopy. Microscopic definitions involving
      the use of Gram stain of cervical secretions have included either more than 10
      white blood cells (WBCs) or more than 30 WBCs per high-power field. Combinations
      of these clinical and microscopic findings have been used in attempts to increase
      the accuracy of cervicitis diagnosis. When cervicitis was initially recognized as
      a clinical entity, several investigators reported the primary pathogens causing
      cervicitis as Neisseria gonorrhoeae and Chlamydia trachomatis. It is now well
      established that most cases of cervicitis are not caused by these two organisms.
      Most cases of cervicitis are of unknown etiology. 

PMID- 24859466
TI  - Optimal timing for cardiac surgery in infective endocarditis: is earlier better?
AB  - All patients with infective endocarditis should be transferred to a hospital with
      cardiac surgery facilities. Once the decision to operate on a patient with
      infective endocarditis has been made, the timing of surgery is very often a
      difficult decision. Literature on this topic is very scarce. The European Society
      of Cardiology guidelines include recommendations on the timing of surgery. Heart
      failure, uncontrolled infection and prevention of embolic risk are the three main
      indications for surgery. Most often, when the decision to operate has been made,
      there is no benefit and potentially harm in delaying surgery. If cardiac surgery
      is indicated after an ischemic stroke, it should not be delayed. Discussion
      should be multidisciplinary and involve at least a cardiologist, a cardiac
      surgeon and an infectious diseases specialist, and any other specialist as needed
      (for example a neurologist). 

PMID- 24859467
TI  - Interventions for improving sit-to-stand ability following stroke.
AB  - BACKGROUND: Standing up from a seated position is one of the most frequently
      performed functional tasks, is an essential pre-requisite to walking and is
      important for independent living and preventing falls. Following stroke, patients
      can experience a number of problems relating to the ability to sit-to-stand
      independently. OBJECTIVES: To review the evidence of effectiveness of
      interventions aimed at improving sit-to-stand ability after stroke. The primary
      objectives were to determine (1) the effect of interventions that alter the
      starting posture (including chair height, foot position, hand rests) on ability
      to sit-to-stand independently; and (2) the effect of rehabilitation interventions
      (such as repetitive practice and exercise programmes) on ability to sit-to-stand
      independently. The secondary objectives were to determine the effects of
      interventions aimed at improving ability to sit-to-stand on: (1) time taken to
      sit-to-stand; (2) symmetry of weight distribution during sit-to-stand; (3) peak
      vertical ground reaction forces during sit-to-stand; (4) lateral movement of
      centre of pressure during sit-to-stand; and (5) incidence of falls. SEARCH
      METHODS: We searched the Cochrane Stroke Group Trials Register (June 2013),
      CENTRAL (2013, Issue 5), MEDLINE (1950 to June 2013), EMBASE (1980 to June 2013),
      CINAHL (1982 to June 2013), AMED (1985 to June 2013) and six additional
      databases. We also searched reference lists and trials registers and contacted
      experts. SELECTION CRITERIA: Randomised trials in adults after stroke where: the
      intervention aimed to affect the ability to sit-to-stand by altering the posture
      of the patient, or the design of the chair; stated that the aim of the
      intervention was to improve the ability to sit-to-stand; or the intervention
      involved exercises that included repeated practice of the movement of sit-to
      stand (task-specific practice of rising to stand).The primary outcome of interest
      was the ability to sit-to-stand independently. Secondary outcomes included time
      taken to sit-to-stand, measures of lateral symmetry during sit-to-stand,
      incidence of falls and general functional ability scores. DATA COLLECTION AND
      ANALYSIS: Two review authors independently screened abstracts, extracted data and
      appraised trials. We undertook an assessment of methodological quality for random
      sequence generation, allocation concealment, blinding of outcome assessors and
      method of dealing with missing data. MAIN RESULTS: Thirteen studies (603
      participants) met the inclusion criteria for this review, and data from 11 of
      these studies were included within meta-analyses. Twelve of the 13 included
      studies investigated rehabilitation interventions; one (nine participants)
      investigated the effect of altered starting posture for sit-to-stand. We judged
      only four studies to be at low risk of bias for all methodological parameters
      assessed. The majority of randomised controlled trials included participants who
      were already able to sit-to-stand or walk independently.Only one study (48
      participants), which we judged to be at high risk of bias, reported our primary
      outcome of interest, ability to sit-to-stand independently, and found that
      training increased the odds of achieving independent sit-to-stand compared with
      control (odds ratio (OR) 4.86, 95% confidence interval (CI) 1.43 to 16.50, very
      low quality evidence).Interventions or training for sit-to-stand improved the
      time taken to sit-to-stand and the lateral symmetry (weight distribution between
      the legs) during sit-to-stand (standardised mean difference (SMD) -0.34; 95% CI 
      0.62 to -0.06, seven studies, 335 participants; and SMD 0.85; 95% CI 0.38 to
      1.33, five studies, 105 participants respectively, both moderate quality
      evidence). These improvements are maintained at long-term follow-up.Few trials
      assessing the effect of sit-to-stand training on peak vertical ground reaction
      force (one study, 54 participants) and functional ability (two studies, 196
      participants) were identified, providing very low and low quality evidence
      respectively.The effect of sit-to-stand training on number of falls was
      imprecise, demonstrating no benefit or harm (OR 0.75, 95% CI 0.46 to 1.22, five
      studies, 319 participants, low quality evidence). We judged the majority of
      studies that assessed falls to be at high risk of bias. AUTHORS' CONCLUSIONS:
      This review has found insufficient evidence relating to our primary outcome of
      ability to sit-to-stand independently to reach any generalisable conclusions.
      This review has found moderate quality evidence that interventions to improve sit
      to-stand may have a beneficial effect on time taken to sit-to-stand and lateral
      symmetry during sit-to-stand, in the population of people with stroke who were
      already able to sit-to-stand independently. There was insufficient evidence to
      reach conclusions relating to the effect of interventions to improve sit-to-stand
      on peak vertical ground reaction force, functional ability and falls. This review
      adds to a growing body of evidence that repetitive task-specific training is
      beneficial for outcomes in people receiving rehabilitation following stroke.

PMID- 24859468
TI  - New insight into the RNA interference response against cathepsin-L gene in the
      pea aphid, Acyrthosiphon pisum: molting or gut phenotypes specifically induced by
      injection or feeding treatments.
AB  - RNA interference (RNAi) has been widely and successfully used for gene
      inactivation in insects, including aphids, where dsRNA administration can be
      performed either by feeding or microinjection. However, several aspects related
      to the aphid response to RNAi, as well as the influence of the administration
      method on tissue response, or the mixed success to observe phenotypes specific to
      the gene targeted, are still unclear in this insect group. In the present study,
      we made the first direct comparison of two administration methods (injection or
      feeding) for delivery of dsRNA targeting the cathepsin-L gene in the pea aphid,
      Acyrthosiphon pisum. In order to maximize the possibility of discovering specific
      phenotypes, the effect of the treatment was analyzed in single individual aphids
      at the level of five body compartments: the bacteriocytes, the gut, the embryonic
      chains, the head and the remaining body carcass. Our analysis revealed that gene
      expression knockdown effect in each single body compartment was dependent on the
      administration method used, and allowed us to discover new functions for the
      cathepsin-L gene in aphids. Injection of cathepsin-L dsRNA was much more
      effective on carcass and head, inducing body morphology alterations, and
      suggesting a novel role of this gene in the molting of these insects.
      Administration by feeding provoked cathepsin-L knockdown in the gut and specific
      gut epithelial cell alteration, therefore allowing a better characterization of
      tissue specific role of this gene in aphids. 

PMID- 24859470
TI  - As a novel p53 direct target, bidirectional gene HspB2/alphaB-crystallin
      regulates the ROS level and Warburg effect.
AB  - Many mammalian genes are composed of bidirectional gene pairs with the two genes
      separated by less than 1.0kb. The transcriptional regulation and function of
      these bidirectional genes remain largely unclear. Here, we report that
      bidirectional gene pair HspB2/alphaB-crystallin, both of which are members of the
      small heat shock protein gene family, is a novel direct target gene of p53. Two
      potential binding sites of p53 are present in the intergenic region of
      HspB2/alphaB-crystallin. p53 up-regulated the bidirectional promoter activities
      of HspB2/alphaB-crystallin. Actinomycin D (ActD), an activator of p53, induces
      the promoter and protein activities of HspB2/alphaB-crystallin. p53 binds to two
      p53 binding sites in the intergenic region of HspB2/alphaB-crystallin in vitro
      and in vivo. Moreover, the products of bidirectional gene pair HspB2/alphaB
      crystallin regulate glucose metabolism, intracellular reactive oxygen species
      (ROS) level and the Warburg effect by affecting metabolic genes, including the
      synthesis of cytochrome c oxidase 2 (SCO2), hexokinase II (HK2), and TP53-induced
      glycolysis and apoptosis regulator (TIGAR). The ROS level and the Warburg effect
      are affected after the depletion of p53, HspB2 and alphaB-crystallin
      respectively. Finally, we show that both HspB2 and alphaB-crystallin are linked
      with human renal carcinogenesis. These findings provide novel insights into the
      role of p53 as a regulator of bidirectional gene pair HspB2/alphaB-crystallin
      mediated ROS and the Warburg effect. 

PMID- 24859471
TI  - Loss of ARHGDIA expression is associated with poor prognosis in HCC and promotes
      invasion and metastasis of HCC cells.
AB  - Rho GTPases control a wide range of cellular processes and contribute to tumor
      invasion and metastasis. As a regulator of Rho activity, ARHGDIA is aberrantly
      expressed in several types of tumors and plays different roles in the tumor
      process. To elucidate the role of ARHGDIA in HCC, we investigated the patterns of
      its expression, prognosis and clinical profiles in HCC. Functional assays were
      performed to investigate whether the alteration of ARHGDIA has an effect on cell
      growth, migration and invasion, as well as the status of Rho GTPases. We found
      that ARHGDIA was frequently downregulated in HCC and associated with tumor
      invasion and metastasis. Moreover, ARHGDIA was significantly associated with OS
      and TTR of HCC patients. Low level of ARHGDIA exhibited a decreased postoperative
      OS and a shorter TTR compared those with high levels. Functional assays showed
      that loss of ARHGDIA promoted HCC cell migration and invasion in vitro and lung
      metastasis formation in vivo. We found that loss of ARHGDIA significantly induced
      Rac1 and RhoA activation which may contribute to invasion and metastasis of HCC.
      In conclusion, the present study has identified loss of ARHGDIA contributed to
      the processes of hepatic tumorigenesis, in particular invasion and metastasis
      which may provide a potential therapeutic target for HCC.

PMID- 24859469
TI  - Examining the impact of gene variants on histone lysine methylation.
AB  - In recent years, there has been a boom in the amount of genome-wide sequencing
      data that has uncovered important and unappreciated links between certain genes,
      families of genes and enzymatic processes and diseases such as cancer. Such
      studies have highlighted the impact that chromatin modifying enzymes could have
      in cancer and other genetic diseases. In this review, we summarize characterized
      mutations and single nucleotide polymorphisms (SNPs) in histone lysine
      methyltransferases (KMTs), histone lysine demethylases (KDMs) and histones. We
      primarily focus on variants with strong disease correlations and discuss how they
      could impact histone lysine methylation dynamics and gene regulation.

PMID- 24859472
TI  - Metastatic potential in MDA-MB-231 human breast cancer cells is inhibited by
      proton beam irradiation via the Akt/nuclear factor-kappaB signaling pathway.
AB  - A previous study has revealed that proton beam irradiation affects cell migration
      in MDA-MB-231 human breast cancer cells. Cyclooxygenase-2 (COX-2) and matrix
      metalloproteinase-9 (MMP-9) are highly expressed in various cancers, such as
      colon, lung and breast cancer, and enhance cell migration and metastasis in vitro
      and in vivo. In the present study, the effects of proton beam irradiation on COX
      2 and MMP-9 expression levels in MDA-MB-231 human breast cancer cells were
      investigated, along with the signaling pathway involved in the proton beam
      irradiation-mediated antimetastatic effect. The results revealed that 12-O
      tetradecanoylphorbol-13-acetate-induced increases in COX-2 and MMP-9 expression
      levels were reversed by proton beam irradiation in a dose-dependent manner. In
      addition, proton beam irradiation inhibited phosphorylation of protein kinase B
      (also known as Akt) and nuclear factor-kappaB (NF-kappaB), which are activated by
      phosphoinositide 3-kinase (PI3K) stimulation. MMP-9 and COX-2 expression levels
      are regulated by PI3K/Akt and/or protein kinase C/mitogen-activated protein
      kinase signaling pathways that enhance NF-kappaB and activator protein-1
      transcriptional activities. Therefore, the results suggest that proton beam
      irradiation inhibited the cancer cell growth and metastasis associated with COX-2
      and MMP-9 expression in MDA-MB-231 human breast cancer cells, and that the
      antimetastatic effect of proton beam irradiation is achieved by the suppression
      of NF-kappaB phosphorylation via inhibition of Akt activation. 

PMID- 24859473
TI  - Treatment of Iron-Loaded Veterinary Sarcoma by Artemisia annua.
AB  - Artemisinin, a constituent of Artemisia annua L., is a well-known antimalarial
      drug. Artemisinin-type drugs also inhibit cancer growth in vitro and in vivo.
      Herbal extracts of A. annua inhibit the growth of cancer cell lines. Here, we
      report on the use of capsules containing powder of Herba Artemisiae annuae to
      treat pet sarcoma. The surgical tumor removal as standard treatment was
      supplemented by adjuvant therapy with A. annua. One cat and one dog with
      fibrosarcoma survived 40 and 37 months, respectively, without tumor relapse. Two
      other dogs suffering from fibrosarcoma and hemangioendothelial sarcoma also
      showed complete remission and are still alive after 39 and 26 months,
      respectively. A. annua was well tolerated without noticeable side effects. These
      four cases indicate that A. annua may be a promising herbal drug for cancer
      therapy. 

PMID- 24859474
TI  - Cardiac manifestations in HIV infected children.
AB  - OBJECTIVE: To determine the occurrence of cardiac involvement in HIV infected
      children and describe its spectrum using non-invasive tests like ECG and 2
      Dimensional Echocardiography (2-D ECHO). METHODS: A cross sectional observational
      study was carried out on 100 HIV infected children between 1 and 18 y of age. The
      various cardiac manifestations were determined clinically, by electrocardiogram
      (ECG) and 2-D echocardiography. RESULTS: Seventy four percent of the patients
      were males with a mean age of 9.62 +/- 3.62 y. Seventy seven percent children
      were in WHO stage I. Sixty five percent did not have significant immune
      suppression. Eighty six percent children were on HAART (mean duration- 35.12 +/-
      29.48 mo). Fifty nine percent of children were symptomatic and only nine patients
      were clinically suspected to have cardiac involvement. ECG abnormalities were
      found in 14 % cases. The most common abnormal echocardiographic finding was left
      ventricular diastolic dysfunction by tissue Doppler (E/E') observed in 64 % cases
      followed by systolic dysfunction (37 %), abnormal left ventricular mass (29 %),
      pericardial effusion (2 %) and dilated cardiomyopathy (2 %); 64.2 % cases with
      left ventricular systolic dysfunction (LVSD) were in WHO stage III. CONCLUSIONS:
      Involvement of heart in HIV/AIDS is mostly subclinical. HIV myocarditis produces
      systolic as well as diastolic dysfunction. At present, echocardiography remains
      the only tool for identifying heart involvement in HIV-infected children. Early
      diagnosis and intervention may halt the progression of the disease, thereby
      preventing morbidity and mortality.

PMID- 24859476
TI  - Macular hole repair by vitrectomy and internal limiting membrane peeling in
      highly myopic eyes.
AB  - PURPOSE: To evaluate the surgical outcomes of macular hole (MH) repair by
      vitrectomy and internal limiting membrane peeling in highly myopic eyes. METHODS:
      In this retrospective interventional case series, 30 highly myopic eyes with MH
      in 29 consecutive patients who underwent vitrectomy and internal limiting
      membrane peeling to repair MH were studied. The mean follow-up time was 36.4
      months. The anatomical outcomes of the MH were evaluated by optical coherence
      tomography. The best-corrected visual acuities before and after surgery were
      compared as the functional outcome. RESULTS: Women accounted for 69% of MH in
      highly myopic eyes. The mean age was 49 years. The mean refraction error and mean
      axial length were -9.80 (+/- 2.93) diopter and 28.13 (+/- 2.41) mm, respectively.
      Myopic foveoschisis was observed in 3 eyes (10%). The MHs were closed by a single
      surgery in 26 eyes (87%), and the final closure rate was 97% (29/30 eyes).
      Macular hole surgery significantly improved best-corrected visual acuity from
      1.20 +/- 0.70 to 0.77 +/- 0.51 logarithm of the minimum angle of resolution (P =
      0.003). However, rhegmatogenous retinal detachment developed in 3 eyes (10%)
      during the follow-up. CONCLUSION: Vitrectomy with internal limiting membrane
      peeling is effective to repair MH in highly myopic eyes in terms of anatomical
      and functional outcomes, although visual acuity may continue to improve slowly
      until 3 years after successful MH-closing surgery. In addition, a small
      proportion of MH cases were associated with myopic foveoschisis. Delayed hole
      closure and rhegmatogenous retinal detachment may occur in these highly myopic
      eyes after surgery.

PMID- 24859475
TI  - Retina specialists treating age-related macular degeneration recommend different
      approaches for patients than they would choose for themselves.
AB  - PURPOSE: To evaluate the presence of cognitive biases among retina physicians
      when recommending treatment options for exudative age-related macular
      degeneration. METHODS: Two random samples of retina specialists were surveyed
      regarding their treatment and dosing regimen choices among three anti-vascular
      endothelial growth factor biologics (aflibercept, bevacizumab, and ranibizumab).
      One group was asked to provide recommendations for a standardized hypothetical
      patient with exudative age-related macular degeneration, whereas the other group
      was asked to provide recommendations as if they themselves were the standardized
      hypothetical patient with exudative age-related macular degeneration. RESULTS:
      Two hundred and twenty-six respondents (28.3%) completed the survey and were
      divided equally between the survey groups. For patients, most physicians
      recommended bevacizumab (52.2%), but when choosing for themselves, physicians
      were divided equally among all 3 biologics (P = 0.011). The results were
      influenced by geographical location of the physician but not by the gender or
      length of practice. Furthermore, physicians differed in dosing regimen selection
      with the majority (73%) choosing treat and extend for patients, whereas only 63%
      selected this regimen for themselves (P = 0.004). CONCLUSION: When considering
      cases of exudative age-related macular degeneration, physicians would recommend
      different treatments for themselves than they would for a patient.

PMID- 24859477
TI  - Morphologic features and evolution of inner retinal dimples on optical coherence
      tomography after internal limiting membrane peeling.
AB  - PURPOSE: To evaluate morphologic features and the evolution of inner retinal
      dimples using spectral domain optical coherence tomography after internal
      limiting membrane peeling. METHODS: A single-center retrospective study of
      spectral domain optical coherence tomography features in 43 eyes after full
      thickness macular hole surgery with internal limiting membrane peeling without
      adjunctive internal limiting membrane staining. RESULTS: Postoperatively, a total
      of 210 dimples were noted in 37 eyes (86%), with a mean of 5.7 dimples per eye
      (median, 5; range, 1-20), most frequently located in the inferotemporal quadrant
      (n = 122, 58%, P < 0.0001). At initial detection, mean dimple dimensions were 199
      MUm wide (median, 183; range, 87-442 MUm) and 19 MUm deep (median, 17; range, 7
      35 MUm). During follow-up, mean maximum dimensions were 351 MUm wide (median,
      305; range, 219-494 MUm) and 30 MUm deep (median, 31; range, 15-55 MUm). Dimple
      dimension reached a maximum at 12 months (median, 10; range, 2-22 months)
      followed by a modest decline. Mean preoperative and final postoperative visual
      acuity were 0.70 logMAR (median, 0.54; range, 0.09-1.4 logMAR) and 0.38 logMAR
      (median, 0.30; range, 0-1.4 logMAR), respectively. CONCLUSION: Inner retinal
      dimples are common after adjunct-free internal limiting membrane peeling and
      evolve in the postoperative period with enlargement over the first 12 months
      followed by reduction in size, and have no apparent impact on the visual acuity.

PMID- 24859478
TI  - Geriatric frailty applied to fibromyalgia patients.

PMID- 24859479
TI  - High-level expression and purification of recombinant human growth hormone
      produced in soluble form in Escherichia coli.
AB  - Human growth hormone (hGH) was one of the first recombinant proteins approved for
      the treatment of human growth disorders. Its small size (191 amino acids),
      possession of only 2 disulphide bonds and absence of posttranslational
      modifications make Escherichia coli the host of choice for its production on any
      scale. In this work, we have utilized an efficient T7 based expression system to
      produce high levels of soluble thioredoxin-hGH (Trx-hGH) fusion protein. We
      outline a relatively simple three step purification process employing two
      immobilized metal-affinity chromatography and one anion-exchange steps and
      removal of fusion partner by enterokinase cleavage yielding native hGH. The
      ability of cell populations to produce quantities of up to 1 g/L of the soluble
      Trx-hGH fusion protein has been tested in flask cultivations as well as in batch
      and fed-batch bioreactor runs. The sequence and structure of derived hGH were
      confirmed by mass spectrometry and circular dichroism and its native function, to
      induce cell proliferation, was confirmed by employing a Nb2 cell line
      proliferation assay.

PMID- 24859480
TI  - Generation of induced pluripotent stem cells derived from primary and secondary
      myelofibrosis patient samples.
AB  - Induced pluripotent stem cells (iPS) derived from disease cells are expected to
      provide a new experimental material, especially for diseases from which samples
      are difficult to obtain. In this study, we generated iPS from samples from
      patients with primary and secondary myelofibrosis. The primary myelofibrosis
      cells had chromosome 13q deletions, and the secondary myelofibrosis (SMF) cells
      had JAK2V617F mutations. The myelofibrosis patient cell-derived iPS (MF-iPS) were
      confirmed as possessing these parental disease-specific genomic markers. The
      capacity to form three germ layers was confirmed by teratoma assay. By co-culture
      with specific feeder cells and cytokines, MF-iPS can re-differentiate into blood
      progenitor cells and finally into megakaryocytes. We found that mRNA levels of
      interleukin-8, one of the candidate cytokines related to the pathogenesis of
      myelofibrosis, was elevated predominantly in megakaryocytes derived from MF-iPS.
      Because megakaryocytes from myelofibrosis clones are considered to produce
      critical mediators to proliferate fibroblasts in the bone marrow and iPS can
      provide differentiated cells abundantly, the disease-specific iPS we established
      should be a good research tool for this intractable disease. 

PMID- 24859481
TI  - Being creative with old tools: the dilating balloon as a weapon against difficult
      bile duct stones.

PMID- 24859482
TI  - Celastrol inhibits the HIF-1alpha pathway by inhibition of mTOR/p70S6K/eIF4E and
      ERK1/2 phosphorylation in human hepatoma cells.
AB  - Hypoxia-inducible factor-1 (HIF-1) is the central mediator of cellular responses
      to low oxygen and vital to many aspects of cancer biology. In a search for HIF-1
      inhibitors, we identified celastrol as an inhibitor of HIF-1 activation from
      Tripterygium wilfordii. In the present study, we demonstrated the effect of
      celastrol on HIF-1 activation. Celastrol showed a potent inhibitory activity
      against HIF-1 activation induced by hypoxia in various human cancer cell lines.
      This compound markedly decreased the hypoxia-induced accumulation of HIF-1alpha
      protein dose-dependently, whereas it did not affect the expressions of HIF-1beta
      and topoisomerase-I (topo-I). Furthermore, celastrol prevented hypoxia-induced
      expression of HIF-1 target genes for vascular endothelial growth factor (VEGF)
      and erythropoietin (EPO). Further analysis revealed that celastrol inhibited HIF
      1alpha protein synthesis, without affecting the expression level of HIF-1alpha
      mRNA or degradation of HIF-1alpha protein. Markedly, we found that suppression of
      HIF-1alpha accumulation by celastrol correlated with strong dephosphorylation of
      mammalian target of rapamycin (mTOR) and its effectors, ribosomal protein S6
      kinase (p70S6K) and eukaryotic initiation factor 4E (eIF4E) and extracellular
      signal-regulated kinase (ERK), pathways known to regulate HIF-1alpha expression
      at the translational level. In vivo studies further confirmed the inhibitory
      effect of celastrol on the expression of HIF-1alpha proteins, leading to a
      decreased growth of Hep3B cells in a xenograft tumor model. Our data suggested
      that celastrol is an effective inhibitor of HIF-1 and provide new perspectives
      into the mechanism of its anticancer activity.

PMID- 24859483
TI  - Sleep disordered breathing, hypoxia and inflammation: associations with sickness
      behaviour in community dwelling elderly with and without cardiovascular disease.
AB  - BACKGROUND: Inflammation can induce a cluster of symptoms, referred to as
      sickness behaviour (e.g., depressive symptoms, sleep disturbances, pain and
      fatigue). Cardiovascular disease (CVD) and sleep disordered breathing (SDB) are
      common in older adults. CVD is associated with an increased inflammatory activity
      and in SDB, hypoxia can also increase inflammation. The purpose of this study is
      to explore if SDB-related hypoxia is associated differently with inflammation and
      the presence of sickness behaviour in older adults with and without CVD. METHODS:
      Three hundred and thirty-one older adults, whose mean age is 78 years, underwent
      one-night polygraphic recording to measure SDB and hypoxia. CVD was established
      by a clinical investigation. Questionnaires were used to measure sickness
      behaviour and depressive symptoms. High sensitivity C-reactive protein was used
      as a marker of inflammation. RESULTS: Structural Equation Modelling showed that
      SDB-related hypoxia was associated with inflammation (beta > 0.40) which mediated
      indirect associations with sickness behaviour (beta = 0.19) and depressive
      symptoms (beta = 0.11), but only in those with CVD (n = 119). In this model,
      inflammation had a direct effect on sickness behaviour (beta = 0.43) and an
      indirect effect on depressive symptoms (beta = 0.24). Hypoxia had the strongest
      effect (i.e., beta = 0.41; significant) on inflammation, whereas the AHI or ODI
      had weak and non-significant effects (beta = 0.03 and beta = 0.15). CONCLUSIONS:
      Older adults with CVD and SDB are at a particular risk of developing sickness
      behaviour and depressive symptoms. The effect of SDB was mainly caused by
      hypoxia, suggesting that hypoxia is an important marker of SDB severity in older
      adults with CVD.

PMID- 24859485
TI  - Altered transport of lindane caused by the retention of natural particles in
      saturated porous media.
AB  - Attachment and straining of colloidal particles in porous media result in their
      reversible and irreversible retention. The retained particles may either increase
      the retention of hydrophobic pollutants by sorption onto the particles, or
      enhance pollutant transport when particles, loaded with the pollutants, are
      remobilized. The present study examines the effects of retained particles on the
      transport of the hydrophobic pesticide lindane (gamma-hexachlorocyclohexane) in
      saturated porous media. The lignite particles used have median diameters of about
      3 MUm, 1 MUm, 0.8 MUm, and 0.2 MUm, respectively. Laboratory column experiments
      were analyzed by numerical modeling in order to identify and understand the
      processes involved in the transport of the particles and of lindane. Four
      scenarios were considered in which the solution containing lindane is injected
      either during or after the elution of the particles. The results show that
      lignite particles retained in a sandy porous medium alter the transport of the
      invading lindane. Particle retention was high in all scenarios and increased with
      increasing particle size. Remobilization of particles occurred due to a change in
      solution chemistry, and continuous particle detachment was observed over time.
      Numerical modeling of particle transport suggests that both reversible attachment
      and irreversible straining affected the transport of the particles. Lindane was
      retarded in all scenarios due to the strong particle retention in conjunction
      with the sorption of lindane onto the sand and onto retained particles, and the
      limited number of mobile particles carrying lindane. Moreover, it was found that
      intra-particle diffusion limited adsorption/desorption of lindane onto/from both
      limestone fragments of the sand and lignite particles. We assume that retention
      of lindane is reversible even though lindane recovery was incomplete over the
      duration of the experiments. The analysis of the effluent concentration suggests
      that retained particles loaded with lindane may become a secondary source of
      lindane. Models describing the transport of lindane fitted the experimental data
      very well and indicated the specific contribution of retained particles to the
      retardation of lindane. Since the properties of lignite also known as brown coal
      are similar to those of biochar, the results of the present study could be
      extended to the potential effects of biochar on lindane and other contaminants in
      soils, which would include both their retention and their enhanced transport.
      However, while the transport mechanisms of lindane are similar in water
      unsaturated soils and saturated porous media considered here, the behavior of
      particles is more complex, requiring additional studies.

PMID- 24859484
TI  - European position paper on drug-induced sedation endoscopy (DISE).
AB  - BACKGROUND: Although drug-induced sedation endoscopy (DISE) represents the most
      widespread diagnostic tool for upper airway endoscopic evaluation of snoring and
      obstructive sleep apnea hypopnea syndrome (OSAHS), many controversies exist about
      how to perform the sedation, the indications for DISE, and how to report DISE
      findings. The present position paper reports on a consensus as proposed by a
      group of European experts in the field of DISE after discussion during a recent
      dedicated meeting. METHODS: The authors have evaluated all the available evidence
      reported in the literature and have compared experience among various departments
      in leading European centers in order to provide a standardization of the DISE
      procedure and an in-depth insight in the main aspects of this technique. RESULTS:
      A proposal of the DISE procedure standardization has been achieved with a general
      agreement concerning the terminology, indications, contraindications, required
      preliminary examinations, setting, technical equipment required, staffing, local
      anesthesia and nasal decongestion, patient positioning, basis and special
      diagnostic maneuvers, and the applied sedation drugs and observation windows.
      Otherwise, no consensus has been reached on a scoring and classification system.
      CONCLUSIONS: Although consensus has been reached on several aspects of the DISE
      procedure, some topics remain open to future research, such as a better analysis
      of the importance of positional aspects during DISE and a further comparison of
      the differences in degree, level and pattern of upper airway collapse observed
      during DISE versus during natural sleep and awake endoscopy. Finally, a
      universally accepted scoring and classification system is lacking.

PMID- 24859486
TI  - Analysis of passive motion of para- and retropharyngeal structures during
      swallowing using dynamic magnetic resonance imaging.
AB  - The purpose of this study was to analyze passive motion of the para- and
      retropharyngeal space (PRS) during swallowing using dynamic magnetic resonance
      imaging (MRI). We conducted a preliminary study involving 30 healthy volunteers
      who underwent dynamic MRI. Consecutive MRI axial images were obtained by
      examining the plane parallel to the hard palate at the level of the anterior
      inferior corner of C2. Anterior displacement of the posterior pharyngeal wall
      (PPW) was measured as a motion index of pharyngeal contraction. The displacement
      and internal angle of the bilateral external and internal carotid arteries (ECA
      and ICA) and the bilateral centroids of the PRS area, as well as the increase in
      PRS area, were calculated at rest and at maximum pharyngeal contraction. In most
      participants, the bilateral ECA, ICA, and centroids were anterointernally
      displaced by pharyngeal contraction. The normalized ECA displacement (r = 0.64, r
      (2) = 0.41), normalized ICA displacement (r = 0.60, r (2) = 0.37), and normalized
      centroid displacement (r = 0.43, r (2) = 0.19) were more than moderately
      positively correlated with the normalized PPW displacement. The normalized PRS
      area increase (r = 0.35, r (2) = 0.12) was weakly positively correlated with the
      normalized PPW displacement. These results revealed that PRS area increased as
      the ECA and ICA were drawn anterointernally via its passive motion by pharyngeal
      contraction.

PMID- 24859488
TI  - Risk factors of postoperative morbidity in patients with uncomplicated liver
      hydatid cyst.
AB  - PURPOSE: To determine postoperative morbidity (POM) in patients undergoing
      surgery for uncomplicated hepatic echinococcosis (HE) and determine associations
      with the variable POM looking for possible risk factors for POM. METHODS: Nested
      case-control study. We included patients undergoing surgery for uncomplicated HE
      in two hospitals in Temuco between 2000 and 2012. The main outcome variable was
      development of POM. Other variables of interest were hospital stay, mortality and
      recurrence. Surgical techniques used were pericystectomy and liver resection.
      Descriptive statistics and analytical statistics were applied using T-test, ANOVA
      and Kruskal-Wallis test to compare continuous variables; Chi(2) and Fisher's
      exact test for categorical variables, and logistic regression models were used,
      estimating OR. RESULTS: 126 patients, median age 41 years, 61% female. The
      incidence of POM was 10.3%, with 76.9% Clavien grade I or II. The etiology was
      6.5% and 4.1% of medical and surgical complications, respectively. There was no
      mortality and with a median follow-up of 83 months, recurrence incidence was
      0.8%. Association was found between cases and controls and the variables age,
      alkaline phosphatase, cyst location and hospital stay. Applying regression models
      age (p = 0.002 and OR 1.07) and cyst location (p = 0.003 and OR 3.94) were found
      to be risk factors. CONCLUSIONS: Observed POM is lower and of less severity than
      those previously published. Risk factors were determined.

PMID- 24859489
TI  - Re-print of "Histone extraction protocol from the two model diatoms Phaeodactylum
      tricornutum and Thalassiosira pseudonana".
AB  - Post-translational modifications of histones affect many biological processes by
      influencing higher order chromatin structure that affects gene and genome
      regulation. It is therefore important to develop methods for extracting histones
      while maintaining their native post-translational modifications. While histone
      extraction protocols have been developed in multicellular and single celled
      organisms such as yeast and Arabidopsis, they are inefficient in diatoms that
      have a silica cell wall that is likely to hinder histone extraction. We report in
      this work a rapid and reliable method for extraction of large amounts of high
      quality histones from the two model diatoms Phaeodactylum tricornutum and
      Thalassiosira pseudonana. The protocol is an important enabling step permitting
      downstream applications such as western blotting and mass spectrometry. 

PMID- 24859490
TI  - Evaluation of immune and apoptosis related gene responses using an RNAi approach
      in vaccinated Penaeus monodon during oral WSSV infection.
AB  - In the present study RNA interference was used to elucidate the connection
      between two endogenous genes [Penaeus monodon Rab7 (PmRab7) or P. monodon
      inhibitor of apoptosis (PmIAP)], and selected immune/apoptosis-related genes in
      orally 'vaccinated' shrimp after white spot syndrome virus (WSSV) infection. P.
      monodon were vaccinated by feeding them with formalin inactivated WSSV-coated
      feed. Thereafter, PmRab7 or PmIAP genes were silenced by injecting the shrimps
      with their respective dsRNA. The resulting groups of shrimps, Rab7 and IAP, were
      orally infected with WSSV and the expression of three immune-relevant genes in
      Rab7 group and five apoptosis-related genes in IAP group was evaluated. In the
      Rab7 group, PmToll, PmPPAE 2 and Pm penaeidin genes were down-regulated. The IAP
      silenced shrimps were characterized by down-regulation of Pm caspase, PmERp57,
      Pm14-3-3 epsilon, Pm ald, and up-regulation of PmSTAT. Thus, silencing of
      PmRab7/PmIAP has provided important clues on their relationship with selected
      immune/apoptosis genes in orally vaccinated P. monodon during WSSV infection. 

PMID- 24859491
TI  - Lack of efficacy of moclobemide or imipramine in the treatment of recurrent brief
      depression: results from an exploratory randomized, double-blind, placebo
      controlled treatment study.
AB  - 'Recurrent brief depression' (RBD) is a common, distressing and impairing
      depressive disorder for which there is no current proven pharmacological or
      psychological treatment. This multicentre, randomized, fixed-dose, parallel
      group, placebo-controlled study of the reversible inhibitor of monoamine oxidase
      moclobemide (450 mg/day) and the tricyclic antidepressant imipramine (150 mg/day)
      evaluated the potential efficacy of active medication, when compared with
      placebo, in patients with recurrent brief depression, recruited in the mid-1990s.
      After a 2-4-week single-blind placebo run-in period, a total of 35 patients were
      randomized to receive double-blind medication for 4 months, but only 16 completed
      the active treatment period. An intention-to-treat analysis of the 34 evaluable
      patients found no evidence for the efficacy of moclobemide or imipramine, when
      compared with placebo, in significantly reducing the severity, duration or
      frequency of depressive episodes. A total of 28 patients experienced at least one
      adverse event, and four patients engaged in nonfatal self-harm. Limitations of
      the study include the small sample size and the high rate of participant
      withdrawal. The lack of efficacy of these antidepressant drugs and the previous
      finding of the lack of efficacy of the selective serotonin reuptake inhibitor
      fluoxetine together indicate that medications other than antidepressant drugs
      should be investigated as potential treatments for what remains a common,
      distressing and potentially hazardous condition. 

PMID- 24859493
TI  - Extensive Mongolian spots in 4p16.3 deletion (Wolf-Hirschhorn syndrome).

PMID- 24859494
TI  - Vocal cord paralysis in association with 9q34 duplication.

PMID- 24859492
TI  - Public health impact and cost-effectiveness of intranasal live attenuated
      influenza vaccination of children in Germany.
AB  - In 2011, intranasally administered live attenuated influenza vaccine (LAIV) was
      approved in the EU for prophylaxis of seasonal influenza in 2-17-year-old
      children. Our objective was to estimate the potential epidemiological impact and
      cost-effectiveness of an LAIV-based extension of the influenza vaccination
      programme to healthy children in Germany. An age-structured dynamic model of
      influenza transmission was developed and combined with a decision-tree to
      evaluate different vaccination strategies in the German health care system. Model
      inputs were based on published literature or were derived by expert consulting
      using the Delphi technique. Unit costs were drawn from German sources. Under base
      case assumptions, annual routine vaccination of children aged 2-17 years with
      LAIV assuming an uptake of 50% would prevent, across all ages, 16 million cases
      of symptomatic influenza, over 600,000 cases of acute otitis media, nearly
      130,000 cases of community-acquired pneumonia, nearly 1.7 million prescriptions
      of antibiotics and over 165,000 hospitalisations over 10 years. The discounted
      incremental cost-effectiveness ratio was <euro> 1,228 per quality-adjusted life
      year gained from a broad third-party payer perspective (including reimbursed
      direct costs and specific transfer payments), when compared with the current
      strategy of vaccinating primarily risk groups with the conventional trivalent
      inactivated vaccine. Inclusion of patient co-payments and indirect costs in terms
      of productivity losses resulted in discounted 10-year cost savings of <euro> 3.4
      billion. In conclusion, adopting universal influenza immunisation of healthy
      children and adolescents would lead to a substantial reduction in influenza
      associated disease at a reasonable cost to the German statutory health insurance
      system. On the basis of the epidemiological and health economic simulation
      results, a recommendation of introducing annual routine influenza vaccination of
      children 2-17 years of age might be taken into consideration.

PMID- 24859495
TI  - Further support for first-trimester disruption causing the oromandibular-limb
      hypogenesis spectrum of anomalies.

PMID- 24859496
TI  - How to predict and diagnose postthrombotic syndrome.
AB  - Postthrombotic syndrome (PTS) is the most frequent complication of deep vein
      thrombosis (DVT). From 20% to 50% of the patients will develop PTS after DVT, and
      from 5% to 10%, severe PTS. PTS is diagnosed on clinical grounds, based on the
      presence of signs and symptoms of venous insufficiency in the leg ipsilateral to
      DVT. The Villalta scale, a clinical scale that incorporates venous symptoms and
      signs, is a recommended standard for the diagnosis of PTS. Identifying which
      patients are at high risk of developing PTS would help improve the management of
      patients with DVT and allow physicians to provide patients with individualized
      information on their expected prognosis. Clinical predictors of PTS have been
      progressively characterized, but the ability to predict which patient with DVT is
      likely to develop PTS remains limited. A number of risk factors for PTS have been
      identified; of these, proximal location of DVT and a previous ipsilateral DVT are
      the most important. This review discusses the knowledge gained over the last
      decade on the diagnosis and predictors of PTS.   

PMID- 24859497
TI  - Right ventricular remodeling due to pulmonary regurgitation is associated with
      reduced left ventricular free wall strain in surgically repaired tetralogy of
      fallot.
AB  - BACKGROUND: The aim of the present study was to assess the impact of pulmonary
      regurgitation (PR) and right ventricle (RV) volume on left ventricle (LV)
      longitudinal strain (LS) in patients with surgically repaired tetralogy of Fallot
      (r-TOF). METHODS AND RESULTS: The study subjects were 32 adolescent asymptomatic
      r-TOF subjects and 30 adolescent healthy controls. Two-dimensional (2-D) and 3
      dimensional (3-D) echocardiography were performed in all subjects using Vivid E9
      (GE Healthcare). On 3-D analysis, LV and RV volumes were measured using 4D auto
      LVEF and TomTec RV analysis. PR fraction (PRF) was calculated by the volumetric
      method (PRF=[RV stroke volume-LV stroke volume]/RV stroke volume). LV-LS was
      assessed on 2-D speckle tracking echocardiography, and "free wall LS" represented
      the average of 3 lateral segments. Although RVEF and LVEF were not different
      between the 2 groups, free wall LS (-17.1 +/- 3.2%) was reduced significantly in
      the r-TOF group compared to the control (-20.5 +/- 4.9%, P=0.008), and correlated
      with the RV variables RVEDVI, RV/LV EDVI ratio and PRF. On multivariate stepwise
      linear regression analysis, RVEDVI was the only risk factor for the reduction of
      free wall LS (P=0.004). CONCLUSIONS: Free wall LS was significantly reduced
      despite preserved LVEF. The severity of LS reduction was correlated with RV
      dilation even in asymptomatic r-TOF patients.

PMID- 24859498
TI  - Enhancement of endothelial function inhibits left atrial thrombi development in
      an animal model of spontaneous left atrial thrombosis.
AB  - BACKGROUND: Left atrial (LA) thrombosis is an important cause of systemic
      embolization. The SPORTS rat model of LA thrombi (Spontaneously-Running Tokushima
      Shikoku), which have a unique characteristic of high voluntary wheel running, was
      previously established. The aim of the present study was to investigate how
      SPORTS rats develop LA thrombi. METHODS AND RESULTS: Nitric oxide (NO) produced
      from cardiovascular endothelial cells plays an important protective role in the
      local regulation of blood flow, vascular tone, and platelet aggregation. No
      evidence of atrial fibrillation or hypercoagulability in SPORTS rats regardless
      of age was found; however, SPORTS rats demonstrated endothelial dysfunction and a
      decrease of NO production from a young age. In addition, endothelial NO synthase
      activity was significantly decreased in the LA and thoracic aorta endothelia of
      SPORTS rats. While voluntary wheel running was able to intermittently increase NO
      levels, running did not statistically decrease the incidence of LA thrombi at
      autopsy. However, L-arginine treatment significantly increased NO production and
      provided protection from the development of LA thrombi in SPORTS rats.
      CONCLUSIONS: They present study results indicate that NO has an important role in
      the development of LA thrombus, and endothelia pathways could provide new targets
      of therapy to prevent LA thrombosis.

PMID- 24859499
TI  - Cardiomyocyte-derived mitochondrial superoxide causes myocardial electrical
      remodeling by downregulating potassium channels and related molecules.
AB  - BACKGROUND: This study was designed to investigate the role of a primary
      hyperoxidative stress in myocardial electrical remodeling using heterozygous
      heart/muscle-specific manganese superoxide dismutase-deficient (H/M-Sod2(+/-))
      mice treated with L-buthionine-sulfoximine (BSO). METHODS AND RESULTS: Both H/M
      Sod2(+/-)and wild-type (WT) mice were treated with intra-peritoneal BSO or saline
      for 7 days, and divided into 4 groups: H/M-Sod2(+/-)+BSO, WT+BSO, H/M-Sod2(+/
      )control, and WT control. The ventricular effective refractory period (ERP) and
      the monophasic action potential duration (MAPD) were determined. Levels of
      oxidative stress, potassium channel-related molecules, and K(+)channel
      interacting protein-2 (KChIP2) were also evaluated. The H/M-Sod2(+/-)+BSO group
      exhibited markedly prolonged MAPD20, MAPD90 and ERP in comparison with the other
      groups (MAPD20: 14 +/- 1 vs. 11 +/- 1 ms, MAPD90: 77 +/- 7 vs. 58 +/- 4 ms, ERP:
      61 +/- 6 vs. 41 +/- 3 ms, H/M-Sod2(+/-)+BSO vs. WT control; P<0.05).
      Mitochondrial superoxide and hydrogen peroxide formation in the myocardium
      increased in the H/M-Sod2(+/-)+BSO group in comparison with the WT+BSO group
      (P<0.05). Real-time RT-PCR and Western blotting revealed that Kv4.2 expression
      was downregulated in both BSO-treated groups, whereas KChIP2 expression was
      downregulated only in the H/M-Sod2(+/-)+BSO group (P<0.05). CONCLUSIONS: BSO
      treatment caused hyperoxidative stress in the myocardium of H/M-Sod2(+/-)mice.
      Changes in the expression and function of potassium channels were considered to
      be involved in the mechanism of electrical remodeling in this model.

PMID- 24859500
TI  - Rare case of homozygous epimerase deficiency and heterozygous of duarte 2
      variant.
AB  - We present a rare case of galactosemia identified by a positive screening test. A
      20-day-old female infant was admitted with jaundice and bloody stained diarrhea.
      There was no history of fever, convulsions, abdominal distention, or bleeding
      from other sites. Laboratory findings indicated elevated total billirubin,
      alanine transaminase, aspartate aminotransferase, alkaline phosphatase, and gamma
      glutamyl transferase. International normalized ratio (INR), prothrombin time (PT)
      and activated partial thromboplastin time (aPTT) were prolonged. Total vitamin D
      was low. Quantitative assay for GALT in hemolysates of RBC: 17 MUmol/min/mg
      protein (normal values: 20-35) (compound heterozygous for D2/N: 16-19). GALE
      level in RBC hemolysate: 11.5 MUmol/h/g Hb (normal values 19-35). Our patient was
      homozygous for the peripheral form of epimerase deficiency galactosemia, as well
      as heterozygous for GALT/(D2) deficiency. She was started on galactose restricted
      diet and vitamin supplementation. At the age of 10 months, the patient appeared
      normal with no signs of developmental delay or eye-cataract.

PMID- 24859501
TI  - Worsening hypertriglyceridemia with oral contraceptive pills in an adolescent
      with HIV-associated lipodystrophy: a case report and review of the literature.
AB  - Abstract We report a case of a 17-year-old girl with a history of congenital
      human immunodeficiency virus (HIV) infection and lipodystrophy secondary to
      highly active antiretroviral therapy (HAART). She developed severe worsening of
      preexisting hypertriglyceridemia after treatment with oral contraceptive pills
      (OCP) for polycystic ovary syndrome. Her hypertriglyceridemia improved upon OCP
      discontinuation. Although it is known that estrogen combined with progestins have
      a negative effect on triglycerides and high-density lipoprotein (HDL) cholesterol
      levels, to our knowledge the association of HAART-related lipodystrophy and
      severe hypertriglyceridemia after OCP use has not been reported in the
      literature. We recommend avoiding the use of OCPs in patients with lipodystrophy
      due to the increased risk of worsening hypertriglyceridemia. 

PMID- 24859502
TI  - Hereditary 1,25-dihydroxyvitamin D-resistant rickets with alopecia in four
      Egyptian families: report of three novel mutations in the vitamin D receptor
      gene.
AB  - OBJECTIVE: To study the vitamin D receptor (VDR) gene in five Egyptian patients
      with severe rickets and the clinical features of hereditary vitamin D-resistant
      rickets, including hypocalcemia, hypophosphatemia, total alopecia, and elevated
      serum levels of 1,25-dihydroxyvitamin D. STUDY DESIGN: We amplified and sequenced
      DNA samples from blood from the patients, their parents, and available family
      members. RESULTS: DNA sequence analyses of the VDR gene showed three novel
      mutations (p.Y295X, p.R343C, and p.R391H) and a previously reported one (p.R30X)
      in four patients, whereas no mutation was found in one patient. Mutations
      cosegregated perfectly with affected individuals in all families, and did not
      exist in unaffected family members or 200 ethnically matched chromosomes.
      CONCLUSION: Three novel deleterious mutations in the VDR ligand-binding domain
      were identified, which are expected to render the VDR nonfunctional. Successful
      treatment with frequent high doses of oral calcium and calcidol was evident in
      all patients; however, hair growth occurred only in one patient.

PMID- 24859503
TI  - Towards an optimization of the management of endocrine complications of
      thalassemia.
AB  - Children with thalassemia are living longer due to better care. Physicians
      dealing with this group of patients now have to contend with new challenges
      resulting from iron overload. Endocrine complications represent the most common
      morbidities encountered. To provide a better quality of life, these complications
      have to be addressed in a consistent way. For this purpose, we have compiled a
      set of recommendations to help physicians provide the best care possible to these
      patients.

PMID- 24859504
TI  - Ovarian hyperstimulation syndrome treated by medroxyprogesterone acetate.
AB  - The activation of the hypothalamic-pituitary-gonadal axis observed during the
      first month of life is thought to be a significant phase in the maturation of
      gonads and potentially be important for the development of reproductive
      functions. The preterm ovarian hyperstimulation syndrome (POHS) was first
      detected at postconception 36-39 weeks in a preterm female newborn with edema
      developing in the vulva, the hypogastric site, and the upper leg. The
      pathophysiology of this postnatal hormonal change is obscure. In this paper we
      would like to present a case developing POHS and to discuss possible
      pathophyslogical mechanisms.

PMID- 24859505
TI  - Ectopic Cushing syndrome secondary to metastatic medullary thyroid cancer in a
      child with multiple endocrine neoplasia syndrome type 2B: clues to early
      diagnosis of the paraneoplastic syndromes.
AB  - We describe a 13-year-old male with multiple endocrine neoplasia syndrome type 2B
      with medullary thyroid carcinoma who was diagnosed with ectopic
      adrenocorticotropin-dependent Cushing syndrome. This report highlights the
      importance of monitoring for paraneoplastic syndrome in MEN and clues to the
      diagnosis of this complication provided by growth patterns.

PMID- 24859506
TI  - Early-onset diabetes mellitus and neurodevelopmental retardation: the first Greek
      case of Wolcott-Rallison syndrome.
AB  - Wolcott-Rallison syndrome (WRS) is a very rare genetic disorder, which is
      transmitted by autosomal recessive inheritance and results from mutations in the
      gene encoding the eukaryotic initiation factor 2-alpha kinase-3 (EIF2AK3). The
      cardinal features of the syndrome include early-onset insulin-dependent diabetes
      mellitus, multiple epiphyseal dysplasia, and growth retardation. We present the
      case of a 13-year-old Greek boy with a known history of infancy-onset diabetes
      mellitus and was found to have WRS at the age of 4 years. He presented with acute
      liver and renal insufficiency in addition to skeletal dysplasia and
      neurodevelopmental retardation. The clinical suspicion of WRS was confirmed by
      molecular analysis of the EIF2AK3 gene. The patient was found to be a compound
      heterozygote with two different novel mutations (c.2776C>T, p.R902X and
      c.3038A>G, p.Y989C). The current patient is one of the longer survivors.

PMID- 24859507
TI  - Lipid patterns in treated growth hormone deficient children vs. short stature
      controls.
AB  - CONTEXT: Previous studies in adults with growth hormone (GH) deficiency have
      substantiated an increased risk of cardiovascular events. This risk has been
      attributed to an unpropitious lipid profile, increased abdominal mass, and higher
      incidence of metabolic syndrome. In these studies, a collateral observation has
      been a negative correlation between IGF-1 levels and lipid profiles. Longitudinal
      studies are lacking in children with GH-deficiency wherein the various lipid
      subfractions after GH treatment were compared to matched GH-sufficient short
      stature controls. Our study examined changes in small lipid particles following
      GH treatment. OBJECTIVE: The primary objective was to determine the effect of GH
      treatment on serum lipids in GH-deficient patients vs. short controls. DESIGN,
      SETTING, AND PARTICIPANTS: This was a prospective, unblinded, case-controlled, 6
      month trial conducted at a tertiary pediatric referral center. Patients were
      referred for short stature. Incorporating accepted criteria, the treatment group
      (n=18) was found to be GH-deficient, whereas the control group (n=13) was GH
      sufficient. The two groups had near-identical short stature along in addition to
      baseline measurements of weight and BMI. INTERVENTIONS: The treatment arm
      received 6 months of recombinant GH at standard doses. MAIN OUTCOME MEASURES: The
      primary endpoint was the comparison of the lipoprotein subclasses and lipids
      between the two groups after 6 months. RESULTS: With the exception of the
      intermediate density lipoprotein (IDL), there were no significant differences at
      baseline in serum lipid profiles between the GH-deficient children and the
      controls. After 6 months of therapy, there were statistically significant
      differences in Apo-B, LDL, and smaller lipoparticles (LDL-3 and non-HDL) in GH
      treated children compared to untreated GH-sufficient short children. CONCLUSIONS:
      Our findings indicate that GH replacement may improve cardiovascular outcome by
      favorably altering lipid profiles.

PMID- 24859508
TI  - Prader-Willi syndrome: a case report with atypical developmental features.
AB  - OBJECTIVE: To describe the case of a male Prader-Willi syndrome (PWS) patient
      with atypical development features. DESCRIPTION: We report the case of a male
      adolescent with confirmed diagnosis of PWS which presents atypical phenotype. The
      patient progressed with spontaneous and complete pubertal development, stature in
      the normal range, and weight control without any pharmacological treatment,
      except metformin. COMMENTS: PWS is an imprinting paternally inherited disorder of
      15q11-13 characterized by hypotonia in infant age, hyperphagia, varied degrees of
      mental retardation, behavior problems, hypogonadism, short stature, and other
      less common findings.

PMID- 24859509
TI  - Neonatal diagnosis of a patient with hypoparathyroidism, sensorineural deafness
      and renal dysplasia (HDR) syndrome associated with cerebral infarction.
AB  - Hypoparathyroidism, sensorineural deafness and renal dysplasia syndrome (HDRS) is
      comprised of a triad of conditions. It is an autosomal dominant condition caused
      by mutations in the GATA3 gene, located at 10p15, a critical region in the
      development of the embryonic parathyroid glands, inner ear, and kidneys. Here we
      describe the case of a patient with all three components of HDR syndrome
      diagnosed in the neonatal period who presented with cerebral infarction,
      hypocalcemia, and renal anomalies. Upon chromosomal microarray he was found to
      have an interstitial deletion at 10p, which produced a partial deletion in the
      GATA3 gene.

PMID- 24859510
TI  - Pubertal gynecomastia: what about the remaining 10%?

PMID- 24859511
TI  - A rare case of familial Cushing's syndrome with a common presentation of weight
      gain due to a mutation of the PRKAR1A gene causing isolated primary pigmented
      nodular adrenocortical disease.
AB  - BACKGROUND: Cushing's syndrome (CS) is uncommon in childhood and adolescence.
      Variable presentation with subtle symptoms and signs can make diagnosis
      difficult. CASE REPORT: We report the case of a 17-year-old girl referred for
      acne and progressive weight gain with an adrenocorticotropic hormone-independent
      CS. A computed tomography scan of the adrenals showed normal-sized adrenal glands
      with discrete bilateral shape irregularity. Bilateral adrenalectomy was performed
      and the histopathological findings were characteristic of primary pigmented
      nodular adrenocortical disease (PPNAD). Genetic analysis confirmed a germline
      mutation of the PRKAR1A gene. The same mutation was found in her sister, mother,
      and maternal grandfather. Endocrine tests showed that the sister of our patient
      also presented PPNAD requiring bilateral adrenalectomy and a similar
      histopathological pattern was observed. No other features of Carney complex was
      found among all affected members of the family. CONCLUSION: It is exceptional for
      PPNAD to be an isolated phenomenon as well as being revealed by progressive
      weight gain in adolescence.

PMID- 24859512
TI  - Chromosome 6q24 transient neonatal diabetes mellitus and protein sensitive
      hyperinsulinaemic hypoglycaemia.
AB  - AIM: We describe the novel clinical observation of protein induced
      hyperinsulinaemic hypoglycaemia following remission of transient neonatal
      diabetes mellitus (TNDM) in a patient with 6q24 methylation defect. METHODS: A
      male infant of non-consanguineous Caucasian parents, born at 40 weeks of
      gestation with a birth weight of 3330 g (-0.55 standard deviation score)
      presented with hyperglycaemia in the first week of life and was diagnosed with
      6q24 TNDM. At 22 months of age, he developed recurrent hypoglycaemic episodes.
      Controlled diagnostic fast, oral glucose tolerance test, protein loading test and
      mixed meal tolerance test were undertaken. Sequencing of ABCC8, KCNJ11, GLUD1 and
      HADH were performed. RESULTS: Investigations suggested a diagnosis of protein
      sensitive hyperinsulinaemic hypoglycaemia with normal serum ammonia,
      acylcarnitine profile and urine organic acids. Sequencing of ABCC8, KCNJ11, GLUD1
      and HADH did not identify a pathogenic mutation to explain his hyperinsulinaemic
      hypoglycaemia. CONCLUSION: This clinical case demonstrates the novel observation
      of protein sensitive hyperinsulinaemic hypoglycaemia in a patient with 6q24 TNDM.
      Long-term follow-up of patients with chromosome 6q24 TNDM is warranted following
      remission.

PMID- 24859513
TI  - An essential splice site mutation (c.317+1G>A) in the TSHR gene leads to severe
      thyroid dysgenesis.
AB  - Congenital hypothyroidism (CH) is the most common neonatal endocrine disorder and
      2% of cases have familial origin. Our aim in this study was to determine the
      genetic alterations in two siblings with CH coming from a consanguineous family.
      Because CH is often inherited in autosomal recessive manner in
      consanguineous/multicase-families, we first performed genetic linkage studies to
      all known causative CH loci followed by conventional sequencing of the linked
      gene. The family showed potential linkage to the TSHR locus, and we detected an
      essential splice site mutation (c.317+1G>A) in both siblings. RT-PCR analysis
      confirmed the functionality of the mutation. The mutation was homozygous in the
      cases whereas heterozygous in carrier parents and an unaffected sibling. Here we
      conclude that thyroid agenesis in both siblings in this study originates from
      c.317+1G>A splice site mutation in the TSHR gene, and this study underlines the
      importance of detailed molecular genetic studies in the definitive diagnosis and
      classification of CH.

PMID- 24859515
TI  - A rare case of pituitary infarction leading to spontaneous tumour resolution and
      CSF-sella syndrome in an 11-year-old girl and a review of the paediatric
      literature.
AB  - Pituitary infarction or apoplexy with spontaneous cure of the underlying
      pituitary adenoma is rare. In the paediatric population, we found only a few
      reported cases. We report a rare case of pituitary infarction progressing to CSF
      sella syndrome (or empty sella) in an 11-year-old girl. She presented with sudden
      onset vomiting, moderate headaches, lethargy, weight loss, and tall stature above
      her mid-parental height. She did not have any severe symptoms of apoplexy. Her
      clinical and radiological findings suggested infarction of a pituitary lesion,
      such as a pituitary adenoma or infarction of a cystic lesion, such as a Rathke's
      cleft cyst. In this report, we discuss her case of probable infarction of a
      growth hormone secreting adenoma with a phase of accelerated growth ending up
      with total anterior pituitary insufficiency. The differential diagnosis and
      review of the rare cases of paediatric pituitary infarction in the literature
      will be discussed.

PMID- 24859514
TI  - Differences in anxiety and depression between male and female caregivers of
      children with a disorder of sex development.
AB  - PURPOSE/BACKGROUND: To examine whether male and female caregivers of children
      with a disorder of sex development (DSD) differ in levels of anxious and
      depressive symptoms. MATERIALS/METHODS: Participants included 80 caregivers (40
      males, 40 females) of 40 children with a DSD. Children were categorized based on
      illness characteristics including ambiguous genitalia, life-threatening, and life
      threatening with ambiguous genitalia. Caregivers completed measures of anxious
      and depressive symptoms. RESULTS: A significant caregiver * diagnosis interaction
      for anxious symptoms emerged, with male caregivers of children with both
      ambiguous genitalia and a life-threatening condition reporting significantly
      lower levels of anxious symptoms than female caregivers of the same children.
      CONCLUSIONS: The findings are surprising because of the low level of anxious
      symptoms reported by male caregivers of children with a complex DSD. It is
      possible that they have disengaged themselves from the child and/or diagnosis,
      causing their female counterparts to take on more responsibility.

PMID- 24859516
TI  - Exposure and health risk assessment of lead in communities of Jimma town,
      southwestern Ethiopia.
AB  - Human beings could be exposed to lead arising from different environmental
      sources, such as air, water and soil. Tap water, air and soil samples were
      collected from four quadrants of Jimma town in southwestern Ethiopia. Eighty
      samples from each environmental source: water, air and soil samples were
      collected and analyzed for lead concentration. Prediction of the blood lead level
      and risk characterization was made using integrated exposure uptake biokinetic
      model and lead risk was calculated using USEPA guideline. Average concentration
      of lead in water, air and soils were 24.55 +/- 10.01, 1.01 +/- 0.41 ug/m(3), and
      220.08 +/- 135.95 ug/g respectively. Uptake of lead by children is significantly
      higher than the adults. The total risk value was 1.41 for children and 0.37 for
      adults. The finding revealed that children are more at risk than adults.

PMID- 24859517
TI  - Humic substances enhance growth and respiration in the basidiomycetes Trametes
      maxima under carbon limited conditions.
AB  - Humic substances (HS) represent the major reservoir of carbon (C) in ecosystems,
      and their turnover is crucial for understanding the global C cycle. Although
      basidiomycetes clearly have a role in HS degradation, much less is known about
      the effect of HS on fungal traits. We studied the alteration of physiological,
      biochemical, and morphological characteristics of Trametes maxima in the presence
      of HS. Both complete medium and minimal (C-limited) medium mimicking natural
      environmental conditions were used. Adding HS led to increased biomass yield, but
      under C-limited conditions the effect was more apparent. This result indicated
      that HS were used as an additional substrate and agreed with data showing a
      greater penetration of tritium-labeled HS into the cell interior under C-limited
      conditions. Humic substances induced ultra-structural changes in fungal cells,
      especially under C limitation, including reducing the thicknesses of the hyphal
      sheath and cell wall. In the minimal medium, cellular respiration increased
      nearly three-fold under HS application, while the corresponding effect in
      complete medium was lower. In addition, in the presence of inhibitors, HS
      stimulated either the cytochrome or the alternative pathway of respiration,
      depending on presence or absence of glucose in the medium. Our results suggest
      that, under conditions mimicking the natural environment, HS may play three major
      roles: as a surplus substrate for fungal growth, as a factor positively affecting
      cell morphology, and as an activator of physiological respiration. 

PMID- 24859519
TI  - High-purity biodiesel production from microalgae and added-value lipid
      extraction: a new process.
AB  - A new process was tested in order to produce and purify biodiesel from microalgae
      lipids and to recover unsaponifiable (added-value) lipids. This process is a two
      step biodiesel production including a saponification reaction step followed by an
      esterification reaction step. The process includes a recovery of the unsaponified
      lipids between both reaction steps. Among the conditions tested, the following
      conditions were found to be the best: temperature for both steps (90  degrees C),
      saponification time (30 min), esterification time (30 min), sulfuric
      acid/potassium hydroxide (1.21, w/w), and methanol-lipid ratio (13.3 mL/g). Under
      these conditions, the fatty acid methyl ester (FAME) yield and the biodiesel
      purity were, respectively, 32% (g FAME/g lipid) and 77% (g FAME/g biodiesel).
      This study also showed that the two-step biodiesel process allows a FAME mass
      composition rich in palmitate (27.9-29.4 wt%), palmitoleate (24.9-26.0 wt%),
      elaidate (14.8-15.2 wt%), and myristate (12.1-13.0 wt%).

PMID- 24859518
TI  - Neomycin inhibition of (+)-7-iso-jasmonoyl-L-isoleucine accumulation and
      signaling.
AB  - The majority of plant defenses against insect herbivores are coordinated by
      jasmonate (jasmonic acid, JA; (+)-7-iso-jasmonoyl-L-isoleucine, JA-Ile)-dependent
      signaling cascades. Insect feeding and mimicking herbivory by application of oral
      secretions (OS) from the insect induced both cytosolic Ca(2+) and jasmonate
      phytohormone elevation in plants. Here it is shown that in Arabidopsis thaliana
      upon treatment with OS from lepidopteran Spodoptera littoralis larvae, the
      antibiotic neomycin selectively blocked the accumulation of OS-induced Ca(2+)
      elevation and level of the bioactive JA-Ile, in contrast to JA level.
      Furthermore, neomycin treatment affected the downstream expression of JA-Ile
      responsive genes, VSP2 and LOX2, in Arabidopsis. The neomycin-dependent reduced
      JA-Ile level is partially due to increased CYP94B3 expression and subsequent JA
      Ile turn-over to12-hydroxy-JA-Ile. It is neither due to the inhibition of the
      enzymatic conjugation process nor to substrate availability. Thus, blocking
      Ca(2+) elevation specifically controls JA-Ile accumulation and signaling,
      offering an insight into role of calcium in defense against insect herbivory. 

PMID- 24859520
TI  - Ginsenosides: prospective for sustainable biotechnological production.
AB  - Panax ginseng C.A. Meyer (ginseng) is a well-known medicinal plant that has been
      traditionally used in the oriental countries for centuries. Wild ginseng is a
      scarce and rare commodity. Field cultivation of the ginseng plant is a time
      consuming and labor-intensive process. Ginsenosides, a group of glycosylated
      triterpenes, also known as saponins, are the principal bioactive constituents of
      ginseng. The use of cell and organ culture processes has been sought as a
      potential alternative for the efficient mass production of ginseng raw material.
      Various bioprocessing strategies have been developed to date. Cells and
      adventitious roots have been cultured in large-scale bioreactors and various
      strategies have been developed accordingly for the enhancement of biomass and
      ginsenoside accumulation. This review highlights the recent progress in the
      cultivation of ginseng cell and organ cultures for the production of ginsenosides
      from bioreactor cultures. In addition, the metabolism and biochemistry of
      ginsenoside biosynthesis, genomic and proteomic studies in ginseng, metabolic
      engineering, biosafety, toxicological evaluation, and efficacy assessment of
      ginseng raw material are also summarized and thoroughly discussed. 

PMID- 24859521
TI  - Influence of the operon structure on poly(3-hydroxypropionate) synthesis in
      Shimwellia blattae.
AB  - Glycerol has become a cheap and abundant carbon source due to biodiesel
      production at a large scale, and it is available for several biotechnological
      applications. We recently established poly(3-hydroxypropionate) [poly(3HP)]
      synthesis in a recombinant Shimwellia blattae strain (Heinrich et al. Appl
      Environ Microbiol 79:3582-3589, 2013). The major drawbacks of the current strains
      are (i) low poly(3HP) yields, (ii) low plasmid stability and (iii) insufficient
      conversion rates. In this study, we demonstrated the influence of alterations of
      the operon structure, consisting of 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. It was
      shown that S. blattae ATCC33430/pBBR1MCS-2::dhaT::pct::aldD::phaC1 synthesized up
      to 14.5 % (wtPHA/wtCDW) in a 2-L fed-batch fermentation process. Furthermore, we
      overcame the problem of plasmid losses during the fermentation period by
      engineering a carbon source-dependent plasmid addiction system in a triose
      phosphate isomerase knockout mutant. An assumed poly(3-hydroxyalkanoic acid)
      degrading activity of the lipase/esterase YbfF could not be confirmed.

PMID- 24859522
TI  - 6S RNA modulates growth and antibiotic production in Streptomyces coelicolor.
AB  - The aim of this study was to contribute to clarifying the role of 6S RNA in the
      development and control of antibiotic biosynthesis in Streptomyces coelicolor.
      Due to the low energetic cost of gene silencing via 6S RNA, it is an easy and
      rapid means of down-regulating the expression of specific genes in response to
      signals from changes in the environment. The expression of 6S RNA in S.
      coelicolor is not constitutive, and its accumulation is adapted to changes in
      nutritional conditions. The 6S RNA of S. coelicolor is capable of interacting
      with RNA polymerase beta beta' subunits and is a template for the transcription
      of short pRNAs. Deletion of the ssrS gene from S. coelicolor affects the growth
      rate and causes changes in the expression of several pathway-specific genes
      involved in actinorhodin biosynthesis. The complementation of the DeltassrS
      strain with ssrS gene restored the wild-type levels of growth and actinorhodin
      production. We conclude that 6S RNA contributes to the optimization of cellular
      adaptation and is an important factor involved in the regulation of growth and
      expression of key genes for the biosynthesis of actinorhodin. 

PMID- 24859523
TI  - Biofilm dynamics characterization using a novel DO-MEA sensor: mass transport and
      biokinetics.
AB  - Biodegradation process modeling is an essential tool for the optimization of
      biotechnologies related to gaseous pollutant treatment. In these technologies,
      the predominant role of biofilm, particularly under conditions of no mass
      transfer limitations, results in a need to determine what processes are occurring
      within the same. By measuring the interior of the biofilms, an increased
      knowledge of mass transport and biodegradation processes may be attained. This
      information is useful in order to develop more reliable models that take biofilm
      heterogeneity into account. In this study, a new methodology, based on a novel
      dissolved oxygen (DO) and mass transport microelectronic array (MEA) sensor, is
      presented in order to characterize a biofilm. Utilizing the MEA sensor, designed
      to obtain DO and diffusivity profiles with a single measurement, it was possible
      to obtain distributions of oxygen diffusivity and biokinetic parameters along a
      biofilm grown in a flat plate bioreactor (FPB). The results obtained for oxygen
      diffusivity, estimated from oxygenation profiles and direct measurements,
      revealed that changes in its distribution were reduced when increasing the liquid
      flow rate. It was also possible to observe the effect of biofilm heterogeneity
      through biokinetic parameters, estimated using the DO profiles. Biokinetic
      parameters, including maximum specific growth rate, the Monod half-saturation
      coefficient of oxygen, and the maintenance coefficient for oxygen which showed a
      marked variation across the biofilm, suggest that a tool that considers the
      heterogeneity of biofilms is essential for the optimization of biotechnologies. 

PMID- 24859524
TI  - A markerless gene replacement method for B. amyloliquefaciens LL3 and its use in
      genome reduction and improvement of poly-gamma-glutamic acid production.
AB  - We herein adapted a markerless gene replacement method by combining a temperature
      sensitive plasmid pKSV7 with a counterselectable marker, the upp gene encoding
      uracil phosphoribosyltransferase (UPRTase), for the poly-gamma-glutamic acid
      (gamma-PGA)-producing strain Bacillus amyloliquefaciens LL3. Deletion of the upp
      gene conferred LL3 5-fluorouracil (5-FU) resistance. Sensitivity to 5-FU was
      restored when LL3 Deltaupp was transformed with pKSV7-based deletion plasmid
      which carries a functional allele of the upp gene of Bacillus subtilis 168. These
      observations allowed us to adapt a two-step plasmid integration and excision
      strategy to perform markerless deletion of genes of interest. Deletion plasmid
      harboring a mutant allele of the target gene was first integrated in the genome
      by culturing cells under nonpermissive conditions for pKSV7 replication. Single
      crossover recombinants were then grown without antibiotics to aid the second
      recombinational event. 5-FU was used to select for double-crossover recombinants
      with plasmid evicted from the chromosome. The resulting recombinants either
      harbored the wild-type or mutated allele of the target gene and could be
      identified by PCR and DNA sequencing. Using this method, we successively removed
      the amyA gene and a 47-kb fragment of the bae cluster from the genome of LL3,
      with higher efficiency compared with previous reports. We also investigated the
      effects of a transcriptional regulator, RocR, on gamma-PGA production and cell
      growth. Specific gamma-PGA production of the rocR mutant was increased by 1.9
      fold, which represents a new way to improve gamma-PGA production. 

PMID- 24859525
TI  - Causal role of spatial attention in arithmetic problem solving: evidence from
      left unilateral neglect.
AB  - Recent behavioural and brain imaging studies have provided evidence for rightward
      and leftward attention shifts while solving addition and subtraction problems
      respectively, suggesting that mental arithmetic makes use of mechanisms akin to
      those underlying spatial attention. However, this hypothesis mainly relies on
      correlative data and the causal relevance of spatial attention for mental
      arithmetic remains unclear. In order to test whether the mechanisms underlying
      spatial attention are necessary to perform arithmetic operations, we compared the
      performance of right brain-lesioned patients, with and without left unilateral
      neglect, and healthy controls in addition and subtraction of two-digit numbers.
      We predicted that patients with left unilateral neglect would be selectively
      impaired in the subtraction task while being unimpaired in the addition task. The
      results showed that neglect patients made more errors than the two other groups
      to subtract large numbers, whereas they were still able to solve large addition
      problems matched for difficulty and magnitude of the answer. This finding
      demonstrates a causal relationship between the ability to attend the left side of
      space and the solving of large subtraction problems. A plausible account is that
      attention shifts help localizing the position of the answer on a spatial
      continuum while subtracting large numbers. 

PMID- 24859526
TI  - Microarray and KOG analysis of Acanthamoeba healyi genes up-regulated by mouse
      brain passage.
AB  - Long-term cultivation in a laboratory could reduce the virulence of Acanthamoeba.
      To identify virulence factors of Acanthamoeba, the authors compared the
      transcription profiles of long-term cultivated Acanthamoeba healyi (OLD) and
      three times mouse-brain passaged A. healyi (MBP) using microarray analysis and
      eukaryotic orthologous group (KOG) assignments. Microarray analysis revealed that
      601 genes were up-regulated by mouse-brain passage. The results of real-time PCR
      of 8 randomly selected genes up-regulated in the MBP strain confirmed microarray
      analysis findings. KOG assignments showed relatively higher percentages of the
      MBP strain up-regulated genes in T article (signal transduction mechanism), O
      article (posttranslational modification, protein turnover, chaperones), C article
      (energy production and conversion), and J article (translation, ribosomal
      structure and biogenesis). In particular, the MBP strain showed higher
      expressions of cysteine protease and metalloprotease. A comparison of KOG
      assignments by microarray analysis and previous EST (expressed sequence tags)
      analysis showed similar populations of up-regulated genes. These results provide
      important information regarding the identification of virulence factors of
      pathogenic Acanthamoeba. 

PMID- 24859527
TI  - Ab initio molecular simulations for proposing novel peptide inhibitors blocking
      the ligand-binding pocket of urokinase receptor.
AB  - Recent biochemical experiments have revealed that a variety of proteases play
      important roles in cancer invasion and metastasis. Among these proteases,
      urokinase-type plasminogen activator (uPA) is particularly important, since its
      specific binding to the receptor (uPAR) existing on the surface of a cancer cell
      is considered to be a trigger for cancer invasion. It is thus expected that the
      blocking of the binding can inhibit cancer invasion in the cancer patients and
      improve their prognosis dramatically. To develop a potent inhibitor for the
      binding, many types of peptides of amino acids were produced and their effect on
      the cancer invasion was investigated in the previous biochemical experiments. On
      the other hand, our previous ab initio molecular simulations have clarified that
      some amino acid residues of uPA play important roles in the specific binding
      between uPA and uPAR. In the present study, we propose some peptides composed of
      these important residues and investigate the specific interactions and the
      binding affinity between uPAR and the peptides at an electronic level, using ab
      initio molecular simulations. Base on the results simulated, we elucidate which
      peptide can bind more strongly to uPAR and propose a novel potent peptide which
      can inhibit the binding between uPAR and uPA efficiently. 

PMID- 24859528
TI  - Oncogenic transformation of diverse gastrointestinal tissues in primary organoid
      culture.
AB  - The application of primary organoid cultures containing epithelial and
      mesenchymal elements to cancer modeling holds promise for combining the accurate
      multilineage differentiation and physiology of in vivo systems with the facile in
      vitro manipulation of transformed cell lines. Here we used a single air-liquid
      interface culture method without modification to engineer oncogenic mutations
      into primary epithelial and mesenchymal organoids from mouse colon, stomach and
      pancreas. Pancreatic and gastric organoids exhibited dysplasia as a result of
      expression of Kras carrying the G12D mutation (Kras(G12D)), p53 loss or both and
      readily generated adenocarcinoma after in vivo transplantation. In contrast,
      primary colon organoids required combinatorial Apc, p53, Kras(G12D) and Smad4
      mutations for progressive transformation to invasive adenocarcinoma-like
      histology in vitro and tumorigenicity in vivo, recapitulating multi-hit models of
      colorectal cancer (CRC), as compared to the more promiscuous transformation of
      small intestinal organoids. Colon organoid culture functionally validated the
      microRNA miR-483 as a dominant driver oncogene at the IGF2 (insulin-like growth
      factor-2) 11p15.5 CRC amplicon, inducing dysplasia in vitro and tumorigenicity in
      vivo. These studies demonstrate the general utility of a highly tractable primary
      organoid system for cancer modeling and driver oncogene validation in diverse
      gastrointestinal tissues. 

PMID- 24859529
TI  - Early development of broadly neutralizing antibodies in HIV-1-infected infants.
AB  - Eliciting protective neutralizing antibodies (NAbs) against HIV-1 is daunting
      because of the extensive genetic and antigenic diversity of HIV-1. Moreover,
      broad and potent responses are uncommon even during persistent infection, with
      only a subset of adults developing broadly neutralizing antibodies (bNAbs) that
      recognize viral variants from different HIV-1 clades. It is not known whether
      bNAbs can also arise in HIV-1-infected infants, who typically progress to disease
      faster than adults, presumably in part due to an immature immune system. Here, we
      show that bNAbs develop at least as commonly in infants as in adults. Cross-clade
      NAb responses were detected in 20/28 infected infants, in some cases within 1
      year of infection. Among infants with breadth of responses within the top
      quartile, neutralization of tier 2 or 3 variants from multiple clades was
      detected at 20 months after infection. These findings suggest that, even in early
      life, there is sufficient B cell functionality to mount bNAbs against HIV-1.
      Additionally, the relatively early appearance of bNAbs in infants may provide a
      unique setting for understanding the pathways of B cell maturation leading to
      bNAbs. 

PMID- 24859530
TI  - Generation of a new therapeutic peptide that depletes myeloid-derived suppressor
      cells in tumor-bearing mice.
AB  - Immune evasion is an emerging hallmark of cancer progression. However, functional
      studies to understand the role of myeloid-derived suppressor cells (MDSCs) in the
      tumor microenvironment are limited by the lack of available specific cell surface
      markers. We adapted a competitive peptide phage display platform to identify
      candidate peptides binding MDSCs specifically and generated peptide-Fc fusion
      proteins (peptibodies). In multiple tumor models, intravenous peptibody injection
      completely depleted blood, splenic and intratumoral MDSCs in tumor-bearing mice
      without affecting proinflammatory immune cell types, such as dendritic cells.
      Whereas control Gr-1-specific antibody primarily depleted granulocytic MDSCs,
      peptibodies depleted both granulocytic and monocytic MDSC subsets. Peptibody
      treatment was associated with inhibition of tumor growth in vivo, which was
      superior to that achieved with Gr-1-specific antibody. Immunoprecipitation of
      MDSC membrane proteins identified S100 family proteins as candidate targets. Our
      strategy may be useful to identify new diagnostic and therapeutic surface targets
      on rare cell subtypes, including human MDSCs. 

PMID- 24859531
TI  - The UPF1 RNA surveillance gene is commonly mutated in pancreatic adenosquamous
      carcinoma.
AB  - Pancreatic adenosquamous carcinoma (ASC) is an enigmatic and aggressive tumor
      that has a worse prognosis and higher metastatic potential than its
      adenocarcinoma counterpart. Here we report that ASC tumors frequently harbor
      somatically acquired mutations in the UPF1 gene, which encodes the core component
      of the nonsense-mediated RNA decay (NMD) pathway. These tumor-specific mutations
      alter UPF1 RNA splicing and perturb NMD, leading to upregulated levels of NMD
      substrate mRNAs. UPF1 mutations are, to our knowledge, the first known unique
      molecular signatures of pancreatic ASC. 

PMID- 24859532
TI  - Detection of a broad range of Leishmania species and determination of parasite
      load of infected mouse by real-time PCR targeting the arginine permease gene
      AAP3.
AB  - Leishmaniasis is one of the world's most neglected infectious diseases, affecting
      around 12 million people and more than 350 million at risk of infection. The
      clinical picture varies from self-healing cutaneous lesions to severe visceral
      infections, but still no commercial vaccines for humans are available and the
      currently used drugs have unpleasant side effects. Here we report a real-time PCR
      assay targeting the arginine permease gene AAP3 that can be applied for all the
      nine different species of the Leishmania genus tested; 4 Old World species and 5
      New World species, from both L. (Leishmania) and L. (Viannia) subgenera. No cross
      reaction was seen with Trypanosoma cruzi, Trypanosoma brucei, human or mouse
      genomic DNA. The assay has a high sensitivity, with a limit of detection of 10fg
      DNA for L. (L.) major and L. (L.) donovani, and 100fg DNA for L. (V.)
      braziliensis, and can be used for both qualitative and quantitative purposes.
      This AAP3-Assay, run in duplex with a host specific gene-assay, was also
      successfully used for quantification of parasite load of footpads from L. (L.)
      major-infected mice. It can therefore be a valuable tool in applications like
      monitoring effects of drugs, the selection of vaccine candidates and in screening
      patients, including asymptomatic carriers. 

PMID- 24859535
TI  - MicroRNA and diseases: therapeutic potential as new generation of drugs.
AB  - MicroRNA (miRNA) is a small non-coding regulatory RNA of 21-25 nucleotides (nts)
      in length. miRNA works as a post-transcriptional regulator of a specific mRNA by
      inducing degradation or translation repression resulting in gene silencing. A
      large number of miRNA have been reported and many more are yet to be discovered.
      Aberrant expression of miRNA has been linked to numerous diseases. Attempts have
      been made to attenuate miRNA misregulation under pathophysiological conditions.
      Additionally, the potential use of miRNA in the diagnosis and treatment of
      diseases has been studied. Several preclinical and clinical results have been
      obtained, and miRNA-based therapeutics are still under investigations. In this
      review, the role of miRNA in a variety of pathological conditions has been
      summarized. Recent findings from preclinical and clinical investigations
      examining the role of miRNA as diagnostic markers, and their potential as drug
      candidates, are also highlighted. The current results summarized in this review
      may elucidate new dimensions of miRNA therapeutic and diagnostic techniques for
      biomedical academic and industry research. 

PMID- 24859534
TI  - Using artificial microRNA sponges to achieve microRNA loss-of-function in cancer
      cells.
AB  - Widely observed dysregulation of microRNAs (miRNAs) in human cancer has led to
      substantial speculation regarding possible functions of these short, non-coding
      RNAs in cancer development and manipulation of miRNA expression to treat cancer.
      To achieve miRNA loss-of-function, miRNA sponge technology has been developed to
      use plasmid or viral vectors for intracellular expression of tandemly arrayed,
      bulged miRNA binding sites complementary to a miRNA target to saturate its
      ability to regulate natural mRNAs. A strong viral promoter can be used in miRNA
      sponge vectors to generate high-level expression of the competitive inhibitor
      transcripts for either transient or long-term inhibition of miRNA function.
      Taking the advantage of sharing a common seed sequence by members of a miRNA
      family, this technology is especially useful in knocking down the expression of a
      family of miRNAs, providing a powerful means for simultaneous inhibition of
      multiple miRNAs of interest with a single inhibitor. Knockdown of overexpressed
      oncogenic miRNAs with the technology can be a rational therapeutic strategy for
      cancer, whereas inhibition of tumor-suppressive miRNAs by the sponges will be
      useful in deciphering functions of miRNAs in oncogenesis. Herein, we discuss the
      design of miRNA sponge expression vectors and the use of the vectors to gain
      better understanding of miRNA's roles in cancer biology and as an alternative
      tool for anticancer gene therapy. 

PMID- 24859536
TI  - A novel predictor for protein structural class based on integrated information of
      the secondary structure sequence.
AB  - The structural class has become one of the most important features for
      characterizing the overall folding type of a protein and played important roles
      in many aspects of protein research. At present, it is still a challenging
      problem to accurately predict protein structural class for low-similarity
      sequences. In this study, an 18-dimensional integrated feature vector is proposed
      by fusing the information about content and position of the predicted secondary
      structure elements. The consistently high accuracies of jackknife and 10-fold
      cross-validation tests on different low-similarity benchmark datasets show that
      the proposed method is reliable and stable. Comparison of our results with other
      methods demonstrates that our method is an effective computational tool for
      protein structural class prediction, especially for low-similarity sequences. 

PMID- 24859533
TI  - In vivo delivery of miRNAs for cancer therapy: challenges and strategies.
AB  - MicroRNAs (miRNAs), small non-coding RNAs, can regulate post-transcriptional gene
      expressions and silence a broad set of target genes. miRNAs, aberrantly expressed
      in cancer cells, play an important role in modulating gene expressions, thereby
      regulating downstream signaling pathways and affecting cancer formation and
      progression. Oncogenes or tumor suppressor genes regulated by miRNAs mediate cell
      cycle progression, metabolism, cell death, angiogenesis, metastasis and
      immunosuppression in cancer. Recently, miRNAs have emerged as therapeutic targets
      or tools and biomarkers for diagnosis and therapy monitoring in cancer. Since
      miRNAs can regulate multiple cancer-related genes simultaneously, using miRNAs as
      a therapeutic approach plays an important role in cancer therapy. However, one of
      the major challenges of miRNA-based cancer therapy is to achieve specific,
      efficient and safe systemic delivery of therapeutic miRNAs in vivo. This review
      discusses the key challenges to the development of the carriers for miRNA-based
      therapy and explores current strategies to systemically deliver miRNAs to cancer
      without induction of toxicity. 

PMID- 24859537
TI  - Substrate profiling of Finegoldia magna SufA protease, inhibitor screening and
      application to prevent human fibrinogen degradation and bacteria growth in vitro.
AB  - SufA, which belongs to the subtilisin-like serine protease family, contains a non
      canonical Asp-His-Ser catalytic triad. Under in vitro conditions, SufA is capable
      of human fibrinogen hydrolysis leading to inhibition of fibrin network formation,
      thus suggesting its important role in the development and progression of
      Finegoldia magna infections. In addition, it has been demonstrated that SufA can
      hydrolyze antibacterial peptides such as LL-37 and the chemokine MIG/CXCL 9,
      hence evading host defence mechanisms. Although the SufA protease from F. magna
      was discovered several years ago, its optimal substrate preference has not yet
      been identified. Considering the role of SufA, we have focused on the profiling
      of its substrate sequence preference spanning S1-S3 binding pockets using the
      FRET (fluorescence resonance energy transfer) approach. Next, based on the
      structure of the P1 residue of the developed substrate, we narrowed the inhibitor
      screening to the phosphonic analogues of amino acids containing an arginine-like
      side chain. Among all the compounds tested, only Cbz-6-AmNphth(P)(OPh)2 showed
      any inhibitory activity against SufA displaying k2/Ki value of 10,800 M(-1) s(
      1). In addition, it prevented SufA-mediated human fibrinogen hydrolysis in vitro
      and exhibited potent antibacterial activity against F. magna, Staphylococcus
      aureus and Escherichia coli. Herein, we report on the substrate specificity,
      synthesis and kinetic evaluation of phosphonic inhibitors of SufA protease from
      F. magna which could help to establish its function in pathogenesis development
      and may lead to the elaboration of new antibacterial drugs.

PMID- 24859538
TI  - Hertwig's epithelial root sheath cell behavior during initial acellular
      cementogenesis in rat molars.
AB  - This study was designed to examine developing acellular cementum in rat molars by
      immunohistochemistry, to elucidate (1) how Hertwig's epithelial root sheath
      disintegrates and (2) whether epithelial sheath cells transform into
      cementoblasts through epithelial-mesenchymal transition (EMT). Initial acellular
      cementogenesis was divided into three developmental stages, which can be seen in
      three different portions of the root: portion 1, where the epithelial sheath is
      intact; portion 2, where the epithelial sheath becomes fragmented; and portion 3,
      where acellular cementogenesis begins. Antibodies against three kinds of matrix
      proteinases, which degrade epithelial sheath-maintaining factors, including
      basement membrane and desmosomes, were used to investigate proteolytic activity
      of the epithelial sheath. Tissue non-specific alkaline phosphatase (TNALP) and
      keratin were used to investigate EMT. Epithelial sheath cells showed
      immunoreactivity for all three enzymes at fragmentation, which suggests that
      epithelial sheath disintegration is enzymatically mediated. Dental follicle cells
      and cementoblasts showed intense immunoreactivity for TNALP, and from portion 1
      through to 3, the reaction extended from the alveolar bone-related zone to the
      root-related zone. Cells possessing keratin/TNALP double immunoreactivity were
      virtually absent. Keratin-positive epithelial sheath cells showed negligible
      immunoreactivity for TNALP, and epithelial cells did not appear to migrate to the
      dental follicle. Together, these findings suggest that a transition phenotype
      between epithelial cells and cementoblasts does not exist in the developing
      dental follicle and hence that epithelial sheath cells do not undergo EMT during
      initial acellular cementogenesis. In brief, this study supports the notion that
      cementoblasts derive from the dental follicle. 

PMID- 24859539
TI  - Rapid guiding catheter swapping for management of rupture during percutaneous
      venoplasty for idiopathic occlusion of superior vena cava.
AB  - Treatment for superior vena cava syndrome (SVCS) by percutaneous interventions
      has become established as a definitive therapy. However, there is a significant
      risk of rupture during SVC intervention. We describe an uncommon case that
      developed SVC rupture during percutaneous intervention for idiopathic SVCS. This
      was managed successfully with pericardiocentesis and rapid implantation of
      covered stent in SVC by rapid guiding catheter swapping technique. This, however,
      led to inadvertent obstruction of left innominate vein which was successfully
      treated by kissing balloon inflation. At 18-month follow-up, he is asymptomatic
      with a well apposed patent stent-graft in the SVC. 

PMID- 24859541
TI  - Psychiatric manifestations of primary Sjogren's syndrome: a case report and
      literature review.
AB  - A 54-year-old woman diagnosed with primary Sjogren's syndrome in 2007 presented
      with a 1-year history of visual hallucinations requiring admission to a
      psychiatric unit. The hallucinations resolved while on olanzapine and
      hydroxychloroquine but recurred when they were stopped. Despite restarting
      olanzapine, her visual hallucinations persisted. When she started a tapering dose
      of prednisolone, all the hallucinations resolved. This report adds to the small
      literature on psychiatric manifestations of Sjogren's syndrome and provides
      evidence that low-dose corticosteroids may be an effective treatment for this
      manifestation. 

PMID- 24859540
TI  - Autoimmune pulmonary proteinosis in a Chilean teenager, a rare aetiology of
      interstitial lung disease.
AB  - Interstitial lung disease (ILD) is rare and encompasses a heterogeneous group of
      diseases, and is even rarer in children than in adults. ILDs compromise more than
      100 different entities, including pulmonary alveolar proteinosis (PAP). There are
      many causes of PAP in children, including surfactant protein gene mutations
      (SFTPB, SFTPC, ABCA3, TTF-1), GMCSF receptor mutations and antigranulocyte
      macrophage colony-stimulating factor autoantibodies. We report a case of a 13
      year-old Chilean girl who presented with an 8-month history of progressive
      exercise intolerance, fatigability and diminished school performance. Physical
      examination revealed resting tachypnoea, a few basal bilateral inspiratory
      crackles, and hypoxaemia on minimal exertion. Clinical suspicion and evaluation,
      including international collaboration, led to the diagnosis of autoimmune PAP and
      specific therapy for the condition. 

PMID- 24859542
TI  - New aetiology of patellofemoral pain syndrome.
AB  - We report the case of a 30-year-old man with more than 100 different male sexual
      partners per year. He reported using cocaine, ecstasy, gamma-hydroxybutyric acid
      and crystal mephedrone and presented with bilateral gonalgia resistant to
      standard analgesia. He had no noteworthy medical history, and physical
      examination and laboratory tests were uninformative. MRI showed marked intra
      articular effusion but no meniscus or ligament damage. The aetiological diagnosis
      in this case was made by excluding other potential causes. Patellofemoral pain
      syndrome (PFPS) is one of the most common and challenging injuries. In this first
      case reported, the aetiology was found to be mechanical, due to the position
      adopted during fellatio with multiple male partners. 

PMID- 24859543
TI  - Deep vein thrombosis and tuberculosis: a causative link?
AB  - Pulmonary tuberculosis is very devastating in developing countries and its
      thrombogenic potential is a disturbing new entity. We report an 18-year-old woman
      who presented with a first episode of deep vein thrombosis. Pulmonary, hepatic
      and splenic tuberculosis was diagnosed while looking for secondary causes. The
      patient was treated with rifampicin, isoniazid, pyrazinamide and ethambutol along
      with low-molecular-weight heparin and antivitamin K. Tuberculosis has several
      mechanisms that induce a hypercoagulable state and can lead to thromboembolic
      complications. 

PMID- 24859544
TI  - Late presentation of a subiliacus haematoma after an apophyseal injury of the
      anterior inferior iliac spine.
AB  - Apophyseal injuries are particularly common in adolescents when the growth spurt
      that accompanies puberty places increased strain on developing bones and muscles.
      Bone growth in particular exceeds that of soft tissues resulting in relatively
      tight musculature and subsequent excessive strain at these sites of tendon
      insertion into bone. We describe a case of a young athlete who presented with
      chronic hip pain after an anterior inferior iliac spine apophyseal injury with
      subsequent haematoma formation under the iliacus muscle. There was no evidence of
      a bleeding disorder. In view of the late presentation, he was managed non
      operatively. This injury requires a low threshold for early cross-sectional
      imaging. The delay in management in this case did not lead to any long-term
      sequelae. 

PMID- 24859545
TI  - When a drug does more than it needs: angio-oedema, an important adverse effect.

PMID- 24859546
TI  - An elusive cause of hypoxaemia in a paediatric patient.
AB  - A 5-year-old girl presented to an ambulatory cardiology clinic with shortness of
      breath, described by the patient's mother and chest discomfort on exertion. At
      this visit, she was noted to have low baseline room air oxygen saturations of
      89%. Subsequent cardiac, respiratory and haematological investigations including
      contrast echocardiography, CT scan of the chest, polysomnography and haemoglobin
      electrophoresis were unhelpful in yielding a diagnosis. A CT scan of the chest
      with contrast was performed which revealed a persistent left-sided superior vena
      cava that appeared to be draining into the left atrium, creating a right-to-left
      shunt. This was not revealed on contrast echocardiography as contrast (micro
      bubbles) had been injected into the right arm. This case report highlights the
      nuances of diagnostic investigations, which without a high index of suspicion may
      exclude a timely diagnosis and therapeutic intervention.

PMID- 24859547
TI  - A rare presentation of an ancient disease: scurvy presenting as orthostatic
      hypotension.
AB  - A 49-year-old man presented to hospital with severe orthostatic hypotension,
      gingival dysplasia and a purpuric rash involving his extremities. The orthostatic
      hypotension failed to respond to fluids and, on the basis of physical examination
      and dietary history, the patient was given a preliminary diagnosis of scurvy
      (ascorbic acid deficiency). Serum ascorbic acid levels were undetectable and the
      orthostasis was resolved within 24 h of ascorbic acid replacement. The
      pathogenesis of orthostatic hypotension in the setting of scurvy appears to
      involve impaired catecholamine synthesis and attenuated vasomotor response to
      alpha-adrenergic stimulation. We believe that this case describes a rare
      presentation of scurvy and highlights a previously under-reported connection
      between scurvy and vasomotor instability.

PMID- 24859548
TI  - Back pain, leg swelling and a cardiac arrest: an interesting case of
      endocarditis.
AB  - A 66-year-old woman with a history of tissue aortic valve replacement and chronic
      back pain presented to the emergency department with a suspected right leg deep
      vein thrombosis. A recent outpatient MRI had revealed discitis. A ventricular
      fibrillation cardiac arrest occurred in the emergency department. Cardiac output
      was restored on the fifth defibrillation. A transthoracic echocardiogram showed
      large aortic valve vegetations. Clinical impression was of infective endocarditis
      with cardiac arrest secondary to coronary artery embolisation. Peripheral blood
      cultures grew Cardiobacterium hominis, and appropriate intravenous antibiotic
      therapy was administered. The infected prosthetic valve was excised. The patient
      experienced postoperative complete heart block and a right hemisphere
      cerebrovascular accident, however she is now recovering well. This case describes
      an unusual case of infective endocarditis secondary to C. hominis, with disc,
      leg, coronary artery and brain septic embolisation. Infective endocarditis is an
      important differential diagnosis in multisystem presentations. 

PMID- 24859549
TI  - An unusual mechanism of foreign body aspiration: a vignette from the emergency
      department.
AB  - A 49-year-old male patient with asthma presented with what appeared to be an
      acute exacerbation of his condition. On closer questioning, he was admitted to
      'inhaling something' that may have been caught in the mouthpiece of his inhaler
      and wondered whether there might be something in his chest. On examination, he
      had a monophonic high-pitched wheeze in his right mid-zone; chest X-ray confirmed
      the presence of a foreign body in his right main bronchus. As it was after normal
      working hours, he was referred for bronchoscopy under the cardiothoracic surgeons
      at St George's. He made a full recovery, and now keeps a used 5 pence coin in a
      jar on his mantelpiece. 

PMID- 24859550
TI  - Nasal CPAP and preterm bradycardia: cause or cure.
AB  - Nasal continuous positive airway pressure (nCPAP) is widely used for the
      treatment of respiratory distress syndrome and apnoea of prematurity.
      Complications related to fixation devices have been well documented. We report a
      clinically well preterm baby suffering intermittent, profound episodes of
      bradycardia without any prior associated apnoea or desaturation. We believe these
      episodes were due to the oculocardiac reflex related to orbital compression from
      the continuous positive airway pressure (CPAP) fixation straps. Bradycardia was
      replicated by gentle ocular compression and the episodes resolved after
      repositioning the CPAP straps. Vagal overstimulation has previously been reported
      in preterm babies but we believe this to be the first case in which pressure from
      CPAP strapping has been reported to trigger bradycardia. However, we suspect that
      similar cases could easily go unrecognised. Careful positioning of CPAP securing
      straps may prevent accidental vagal overstimulation contributing to episodic
      bradycardia. 

PMID- 24859551
TI  - A huge oral pyogenic granuloma with extensive alveolar bone loss and 'sun-ray'
      appearance mimicking a malignant tumour.
AB  - Pyogenic granuloma represents an exuberant connective tissue proliferation due to
      a chronic stimulus or injury. Aetiological factor for this lesion may sometimes
      be hard to identify, but the fact that it is usually located close to the
      gingival margin suggests that calculus, food materials and overhanging
      restorations are important irritants. It rarely grows more than 2 cm in diameter
      and usually does not cause any changes in the alveolar bone. We report an unusual
      case of pyogenic granuloma with unknown aetiology that presented as an
      extraordinarily large sessile bilobular lesion and showed a large radiographic
      defect in the alveolar bone with a sun-ray pattern. This kind of
      clinicoradiological appearance of pyogenic granuloma as presented in our case is
      rare and the first of its kind. 

PMID- 24859552
TI  - Odontogenic myxoma in a 52-year-old woman.
AB  - Odontogenic myxoma (OM) is a rare benign but locally aggressive tumour of the
      jaws. It is usually seen in the second to third decade of life. Women are more
      frequently affected than men and it has more predilections for the mandible
      rather than the maxilla. OM presents as an asymptomatic swelling in most of the
      cases. Owing to the non-capsulated and aggressive nature of OM, a high rate of
      recurrence has been reported. Here we present a case of OM in a 52-year-old woman
      managed by segmental mandibulectomy. Sign of recurrence was seen after 18 months
      of follow-up. 

PMID- 24859553
TI  - The utility of online haemodiafiltration in methotrexate poisoning.
AB  - Summary We report a case of a 56-year-old woman with a high-grade diffuse large B
      cell lymphoma who unexpectedly developed toxic plasma levels of methotrexate
      (MTX) following the first cycle of rituximab-cyclophosphamide,
      hydroxydanorubicin, oncovin, prednisolone (R-CHOP) with a high-dose MTX
      chemotherapy protocol. She also developed non-oliguric acute kidney injury
      secondary to MTX nephrotoxicity. We elected to treat her with online
      haemodiafiltration (HDF) and this proved to be efficient with a dramatic
      response. Rapid clearance of MTX to therapeutic levels was possible within three
      sessions. Prompt therapy with high-volume online-HDF is an effective choice for
      rapid MTX clearance and swift reversal of MTX nephrotoxicity. 

PMID- 24859554
TI  - Invasive pulmonary aspergillosis in a patient presenting with idiopathic systemic
      capillary leak syndrome.
AB  - A 54-year-old man presented to our emergency department with fever and dyspnoea.
      He required vigorous haemodynamic support and mechanical ventilation for
      hypotensive distributive shock with hypoalbuminaemia, haemoconcentration,
      rhabdomyolysis and acute renal failure, consistent with idiopathic systemic
      capillary leak syndrome. Left lung consolidation and hypoxaemia were observed 6
      days after admission. Sputum smear revealed the presence of acute angled
      branching hyphae, consistent with a diagnosis of invasive pulmonary
      aspergillosis. Antifungal therapy was administered and mechanical ventilation
      discontinued on day 66. The patient recovered and was discharged from the
      hospital on day 185.

PMID- 24859555
TI  - Brachial artery pseudoaneurysm.
AB  - We describe a case of an elderly man who presented with an upper arm swelling
      that had developed following a humeral fracture 8 months previously. The swelling
      was painless but associated with significantly diminished motor function of his
      right hand and concurrent paraesthaesia. On examination, a large pulsatile mass
      was identified and CT angiography confirmed the presence of an 11*7 cm brachial
      artery pseudoaneurysm. The patient underwent surgical repair in which a fragment
      of the humerus was found to have punctured the brachial artery resulting in a
      pseudoaneurysm. The patient had an uncomplicated postoperative period and was
      discharged 2 days later having regained some motor function in his right hand.

PMID- 24859556
TI  - Silent sinus syndrome as a recognised cause of unilateral painless enophthalmos.
AB  - An uncommon case of unilateral painless enophthalmos in a 44-year-old woman is
      presented. Despite the noticeable orbital asymmetry caused by enophthalmos, the
      patient has normal visual acuities in both eyes with unremarkable ophthalmic
      examination. Diagnosis of silent sinus syndrome was confirmed on the CT orbits
      and paranasal sinuses, showing complete opacification and atelectasis of the
      maxillary sinus. The patient achieved satisfactory improvements in her nasal
      symptom and facial appearance following functional endoscopic sinus surgery. 

PMID- 24859557
TI  - A rare cause of dilated bile duct incidentally detected on imaging.
AB  - Adenomas involving the extrahepatic bile ducts are rare benign tumours of the
      biliary tract. Given the asymptomatic nature of these tumours and the natural
      progression of biliary adenoma to carcinoma including cholangiocarcinoma, early
      detection is challenging. We present a case of an octogenarian woman with a
      remote history of gallstones who initially presented to the gastroenterology
      office for an incidental finding of biliary dilation, and whose subsequent
      imagings and biopsy suggested common bile adenoma. However, the patient was
      deemed a poor surgical candidate for pancreaticoduodenectomy, and unfortunately
      represented 5 months later with findings suggesting cholangiocarcinoma. This case
      provides a unique opportunity to study the natural progression of biliary adenoma
      to cholangiocarcinoma. 

PMID- 24859558
TI  - Panhypopituitarism secondary to a solitary hypothalamic metastasis.

PMID- 24859559
TI  - Osteoid osteoma as a cause of anterior ankle pain in a runner.
AB  - We report the case of an osteoid osteoma in the dorsal talar neck of a healthy
      long-distance runner, masquerading as anterior ankle impingement syndrome. We
      discuss the diagnosis and successful treatment using percutaneous CT-guided laser
      photocoagulation. A concise review of the principles of the management of osteoid
      osteomas is also presented. 

PMID- 24859560
TI  - An unusual presentation of bilateral Hutch diverticula.
AB  - Summary Hutch diverticula are rare congenital diverticula. The general consensus
      is that they occur secondary to a congenital failure of normal muscle development
      around the ureteral orifice where Waldeyer sheath anatomically covers the space
      between the intravesical ureter and muscular layer of the bladder. Our case
      highlights the radiological appearance of Hutch diverticula and the need for
      contrast-enhanced imaging to enable accurate evaluation and diagnosis. It
      illustrates how the presence of periureteric diverticula can contribute to
      ureteric obstruction and calculus formation; complicate the interpretation of
      renal tract imaging and the subsequent management of renal calculi. 

PMID- 24859561
TI  - Severe mitral regurgitation due to anterior mitral leaflet perforation after
      surgical treatment of discrete subaortic stenosis.
AB  - Congenital subvalvular aortic stenosis may be associated with anomalies of the
      mitral valve. In this case, we present a patient with severe mitral valve
      regurgitation due to a perforation in the anterior mitral leaflet detected 4
      months after an operation for relief of subaortic stenosis. A 10-year-old male
      patient who was operated for subvalvular aortic stenosis in another clinic was
      admitted to our hospital, and transthoracic echocardiography revealed severe
      mitral valve regurgitation due to a defect that was demonstrated at the anterior
      valve leaflet. The perforated area at the mitral valve zone A1 was repaired with
      a PTFE patch. The patient was successfully operated for the mitral valve
      perforation and the postoperative course was uneventful. In our case, the
      perforation in the anterior mitral leaflet implies a possible implementation of
      inappropriate surgical technique which necessitated a second surgical
      intervention after the initial operation. 

PMID- 24859562
TI  - Paediatric ventriculoperitoneal shunt infection caused by Actinomyces neuii.
AB  - We present the first reported case of ventriculoperitoneal shunt infection
      secondary to Actinomyces neuii in a paediatric patient. Our patient was managed
      with temporary shunt removal, intrathecal antibiotics and a prolonged course of
      intravenous and then oral antibiotics. She went on to make a complete recovery.
      Subsequent cerebrospinal fluid analysis at 5 months post-treatment demonstrated
      no evidence of residual infection. 

PMID- 24859563
TI  - Simultaneous shoulder and elbow dislocation.
AB  - Ipsilateral shoulder and elbow dislocation is very rare and only six articles are
      present in the literature mentioning this kind of a complex injury. With this
      presentation we aim to emphasise the importance of assessing the adjacent joints
      in patients with trauma in order not to miss any accompanying pathologies. We
      report a case of a 43-year-old female patient with ipsilateral right shoulder and
      elbow dislocation treated conservatively. The patient reported elbow pain when
      first admitted to emergency service but she was diagnosed with simultaneous
      ipsilateral shoulder and elbow injury and treated conservatively. As a more
      painful pathology may mask the additional ones, one should hasten to help before
      performing a complete evaluation. Any harm caused to the patient due to this
      reason would not be a complication but a malpractice. 

PMID- 24859564
TI  - Giant gallstone in the duodenum.

PMID- 24859565
TI  - Kienbock's disease: insidious unilateral wrist pain.

PMID- 24859567
TI  - Neurostimulation at pterygopalatine fossa for cluster headaches and
      cerebrovascular disorders.
AB  - There are numerous neural structures (parasympathetic, sympathetic, and
      trigeminal sensory) that are compacted in a small well defined area of the
      pterygopalatine fossa (PPF). These targets can be readily accessed via minimally
      invasive neuromodulation techniques making the methods more desirable than
      neurosurgical deep brain or hypothalamic intervention. Recent research has shed
      light over the important role of the sphenopalatine ganglion (SPG), which is
      located within the PPF, in cerebrovascular autonomic physiology as well as in the
      pathophysiology of different headache disorders (cluster headache, migraine, and
      trigeminal autonomic cephalalgias). Accordingly, neuromodulation of the autonomic
      fibers (parasympathetic and sympathetic) may play a key role in the management of
      headaches, stroke, or cerebral vasospasm. Another important structure within the
      PPF is the maxillary nerve (V2), which passes through the roof of the fossa. Here
      the trigeminal system is accessible for a reliable neuromodulation by targeting
      its second branch -the maxillary nerve- and this could be utilized in various
      painful conditions of the head and face.

PMID- 24859566
TI  - Increased O-GlcNAc levels correlate with decreased O-GlcNAcase levels in
      Alzheimer disease brain.
AB  - The potential role of the posttranslational modification of proteins with O
      linked N-acetyl-beta-d-glucosamine (O-GlcNAc) in the pathogenesis of Alzheimer
      disease (AD) has been studied extensively, yet the exact function of O-GlcNAc in
      AD remains elusive. O-GlcNAc cycling is facilitated by only two highly conserved
      enzymes: O-GlcNAc transferase (OGT) catalyzes the addition, while O-GlcNAcase
      (OGA) catalyzes the removal of GlcNAc from proteins. Studies analyzing global O
      GlcNAc levels in AD brain have produced inconsistent results and the reasons for
      altered O-GlcNAcylation in AD are still poorly understood. In this study, we show
      a 1.2-fold increase in cytosolic protein O-GlcNAc modification in AD brain when
      compared to age-matched controls. Interestingly, O-GlcNAc changes seem to be
      attributable to differential modification of a few individual proteins. While our
      finding of augmented O-GlcNAcylation concurs with some reports, it is contrary to
      others demonstrating decreased O-GlcNAc levels in AD brain. These conflicting
      results emphasize the need for further studies providing conclusive evidence on
      the subject of O-GlcNAcylation in AD. We further demonstrate that, while OGT
      protein levels are unaffected in AD, OGA protein levels are significantly
      decreased to 75% of those in control samples. In addition, augmented protein O
      GlcNAc modification correlates to decreased OGA protein levels in AD subjects.
      While OGA inhibitors are already being tested for AD treatment, our results
      provide a strong indication that the general subject of O-GlcNAcylation and
      specifically its regulation by OGA and OGT in AD need further investigation to
      conclusively elucidate its potential role in AD pathogenesis and treatment. 

PMID- 24859568
TI  - Trends in trabecular architecture and bone mineral density distribution in 152
      individuals aged 30-90 years.
AB  - The strength of trabecular bone depends on its microarchitecture and its tissue
      level properties. However, the interrelation between these two determinants of
      bone quality and their relation to age remain to be clarified. Iliac crest bone
      cores (n=152) from individuals aged 30-90 years were analyzed by quantitative
      backscattered electron imaging. Univariate and multivariate analyses were
      conducted to determine whether epidemiological parameters (age, sex or BMI),
      structural histomorphometrical variables (BV/TV, Tb.Th, Tb.N and Tb.Sp) and
      osteoid-related indices (OV/BV, OS/BS or O.Th) predict the degree of bone
      mineralization. While sex and BMI were not associated with bone mineralization,
      age was positively correlated with the most frequently occurring calcium
      concentrations (Ca peak), the percentage of highly mineralized bone areas (Ca
      high) and, in the case of adjusted covariates, also the mean calcium content (Ca
      mean). Bone volume fraction and trabecular thickness were both negatively
      correlated with Ca mean. However, trabecular thickness was additionally
      associated with Ca peak, Ca high as well as the amount of low mineralized bone
      (Ca low) and was the only structural parameter predicting bone mineralization
      independent of age. Furthermore, our analyses demonstrated that osteoid variables
      - within a normal range (<2% OV/BV) - were significantly associated with all
      mineralization parameters and represent the only predictor for the mineralization
      heterogeneity (Ca width). Taken together, we showed that elevated trabecular bone
      mineralization correlates with aging and bone loss. However, these associations
      are attributable to trabecular thinning that comes along with high bone
      mineralization due to the loss of low mineralized bone surfaces. Therefore, we
      demonstrated that the degree of areally resolved bone mineral is primarily
      associated with the amount of physiological osteoid present and the thickness of
      mineralized bone in trabeculae.

PMID- 24859569
TI  - The phosphorylation of Hsp20 enhances its association with amyloid-beta to
      increase protection against neuronal cell death.
AB  - Up-regulation of Hsp20 protein levels in response to amyloid fibril formation is
      considered a key protective response against the onset of Alzheimer's disease
      (AD). Indeed, the physical interaction between Hsp20 and Abeta is known to
      prevent Abeta oligomerisation and protects neuronal cells from Abeta mediated
      toxicity, however, details of the molecular mechanism and regulatory cell
      signalling events behind this process have remained elusive. Using both
      conventional MTT end-point assays and novel real time measurement of cell
      impedance, we show that Hsp20 protects human neuroblastoma SH-SY5Y cells from the
      neurotoxic effects of Abeta. In an attempt to provide a mechanism for the
      neuroprotection afforded by Hsp20, we used peptide array, co-immunoprecipitation
      analysis and NMR techniques to map the interaction between Hsp20 and Abeta and
      report a binding mode where Hsp20 binds adjacent to the oligomerisation domain of
      Abeta, preventing aggregation. The Hsp20/Abeta interaction is enhanced by Hsp20
      phosphorylation, which serves to increase association with low molecular weight
      Abeta species and decrease the effective concentration of Hsp20 required to
      disrupt the formation of amyloid oligomers. Finally, using a novel fluorescent
      assay for the real time evaluation of morphology-specific Abeta aggregation, we
      show that phospho-dependency of this effect is more pronounced for fibrils than
      for globular Abeta forms and that 25mers corresponding to the Hsp20 N-terminal
      can be used as Abeta aggregate inhibitors. Our report is the first to provide a
      molecular model for the Hsp20/Abeta complex and the first to suggest that
      modulation of the cAMP/cGMP pathways could be a novel route to enhance Hsp20
      mediated attenuation of Abeta fibril neurotoxicity.

PMID- 24859570
TI  - Do quantitative magnetic resonance imaging parameters correlate with the clinical
      presentation and functional outcomes after surgery in cervical spondylotic
      myelopathy? A prospective multicenter study.
AB  - STUDY DESIGN: A prospective multicenter cohort study. OBJECTIVE: To establish the
      relationship between preoperative quantitative magnetic resonance imaging (MRI)
      parameters and clinical presentation and postoperative outcomes in patients with
      cervical spondylotic myelopathy. SUMMARY OF BACKGROUND DATA: Correlation of
      magnetic resonance imaging with clinical presentation and outcomes in cervical
      spondylotic myelopathy is poorly understood. METHODS: A total of 134 magnetic
      resonance imaging scans were reviewed from 12 sites across North America. The
      transverse area (TA) of the spinal cord at the site of maximal compression was
      computed, and spinal cord signal intensity (SI) changes on T1-/T2-weighted
      imaging (WI) were evaluated. Detailed clinical assessments--neurological signs,
      symptoms, Nurick grade, modified Japanese Orthopaedic Association, segmental
      tract score, and long-tract score of modified Japanese Orthopaedic Association,
      30-m walk test, Short-Form 36 questionnaire, and neck disability index were
      performed at admission, 6 months, and 12 months postoperatively. RESULTS: The
      total number of neurological signs in a patient correlated with TA (P = 0.01) and
      SI changes on T1-/T2WI (P = 0.05). Pre- and postoperative Nurick grade (P = 0.03,
      P = 0.02), modified Japanese Orthopaedic Association score (P = 0.005, P =
      0.001), segmental-tract score (P = 0.05, P = 0.006), and long-tract score (P =
      0.006, P = 0.002), 30-m walk test (P = 0.002, P = 0.01) correlated with TA. There
      was no significant difference in pre- and postoperative clinical scores in
      patients with/without SI changes. Patients with severe cord compression showed SI
      changes on T1-/T2WI more frequently (r =-0.27, r =-0.38). Pyramidal signs-
      plantar response, Hoffmann reflex and hyper-reflexia correlated with TA (P =
      0.003, P = 0.0004, P = 0.024, respectively) and SI changes on T1/T2WI (P = 0.02).
      CONCLUSION: TA closely mirrors the clinical presentation of cervical spondylotic
      myelopathy and may be used in predicting surgical outcomes. Pyramidal signs
      correlated with TA and/or SI changes on T1-/T2WI. The total number of
      neurological signs in a patient correlated with TA. There was no significant
      relationship between TA, age and duration of symptoms. LEVEL OF EVIDENCE: 3.

PMID- 24859571
TI  - Prevalence and type of cervical deformity among 470 adults with thoracolumbar
      deformity.
AB  - STUDY DESIGN: Multicenter, prospective, consecutive case series. OBJECTIVE: To
      assess prevalence and type of cervical deformity among adults with thoracolumbar
      (TL) deformity and to assess for associations between cervical deformities and
      different types of TL deformities. SUMMARY OF BACKGROUND DATA: Cervical deformity
      can present concomitantly with TL deformity and have implications for the
      management of TL deformity. METHODS: Multicenter, prospective, consecutive series
      of adult (age >18 yr) patients with TL deformity. Parameters included pelvic tilt
      (PT), pelvic incidence (PI), lumbar lordosis (LL), C2-C7 sagittal vertical axis
      (C2-C7SVA), C7-S1SVA, and C2-C7 lordosis. Cervical deformity was defined as
      cervical lordosis more than 0 degrees  (cervical kyphosis [CK]) or C2-C7SVA more
      than 4 cm (cervical positive sagittal malalignment [CPSM]). Patients were
      stratified by the Scoliosis Research Society-Schwab classification of adult TL
      deformity, including curve type (N = sagittal deformity, T = thoracic scoliosis,
      L = lumbar scoliosis, and D = T + L scoliosis) and modifier grades: PT (0: <20
      degrees , +: 20 degrees -30 degrees , ++: >30 degrees ), C7-S1SVA (0: <4 cm, +: 4
      9.5 cm, ++: >9.5 cm), and PI-LL mismatch (0: <10 degrees , +: 10-20 degrees , ++:
      >20 degrees ). RESULTS: A total of 470 patients met criteria (mean age = 52 yr).
      Mean cervical lordosis and C2-C7SVA were -8 degrees  and 3.2 cm, respectively. CK
      and CPSM prevalence were 31% and 29%, respectively, and prevalence of CK and/or
      CPSM was 53%. CK prevalence differed by curve type (N = 15%, L = 27%, D = 37%, T
      = 49%; P < 0.001); CPSM prevalence did not differ by curve type (P = 0.19).
      Higher PT grades had lower CK prevalence (0 = 40%, += 27%, ++= 15%; P < 0.001)
      but greater CPSM prevalence (0 = 23%, += 28%, ++= 45%; P = 0.001). Similarly,
      higher SVA grades had lower CK prevalence (0 = 40%, += 23%, ++= 11%; P < 0.001)
      but greater CPSM prevalence (0 = 24%, += 24%, ++= 48%; P < 0.001). Higher PI-LL
      grades had lower CK prevalence (0 = 35%, += 31%, ++= 22%; P = 0.034) but no CPSM
      association (P = 0.46). CONCLUSION: Cervical deformity is highly prevalent (53%)
      in adult TL deformity. C7-S1SVA, PT, and PI-LL modifiers are associated with
      cervical deformity prevalence. These findings suggest that TL deformity
      evaluation should include assessment for concomitant cervical deformity and that
      further study is warranted to define their potential clinical impact. LEVEL OF
      EVIDENCE: 3.

PMID- 24859572
TI  - Reliability and validity of the Persian versions of the fear avoidance beliefs
      questionnaire and Tampa Scale of Kinesiophobia in patients with neck pain.
AB  - STUDY DESIGN: Validation of 2 self-report questionnaires. OBJECTIVE: To evaluate
      the internal consistency, reliability, and construct validity of the Persian
      versions of the fear avoidance beliefs questionnaire (FABQ) and the Tampa Scale
      of Kinesiophobia (TSK) in patients with acute and chronic neck pain. SUMMARY OF
      BACKGROUND DATA: The FABQ and TSK are 2 important measures to evaluate fear of
      pain and fear avoidance beliefs in patients with spinal pain. To date, the
      psychometric properties of these questionnaires have not been demonstrated in
      Persian-speaking patients with neck pain in Iran. METHODS: One hundred sixty-six
      patients with acute and chronic neck pain participated in the study. The
      construct validity of the questionnaires was evaluated by measuring convergent
      and known-groups validity. The visual analogue scale measure of pain, neck
      disability index, hospital anxiety and depression scale, and the physical (PCS
      12) and mental (MCS-12) summary scores of the Short Form health survey (SF-12)
      were used to test construct validity of the Persian FABQ and TSK. In addition, 50
      randomly selected patients with chronic neck pain were asked to complete the
      questionnaires 48 hours later for the second time. RESULTS: Cronbach alpha
      coefficient for the FABQ and TSK in patients with acute and chronic pain was in
      the range from 0.77 to 0.92 and 0.77 to 0.78, respectively. The Persian FABQ and
      TSK showed satisfactory test-retest reliability with intraclass correlation
      coefficient of more than 0.80. There were moderate to strong correlations between
      the Persian FABQ and TSK scores and the neck disability index (r = 0.44-0.55),
      Depression subscales of the hospital anxiety and depression scale (r = 0.42
      0.48), and PCS-12 (r =-0.34 to -0.62). CONCLUSION: The Persian FABQ and TSK have
      acceptable reliability and validity for measuring pain related fear and avoidance
      beliefs among Persian-speaking patients with acute and chronic neck pain.
      However, considering the study limitations, the findings should be interpreted
      with caution. LEVEL OF EVIDENCE: 3.

PMID- 24859573
TI  - Effects of sagittal endplate shape on lumbar segmental mobility as evaluated by
      kinetic magnetic resonance imaging.
AB  - STUDY DESIGN: Retrospective analysis using kinetic magnetic resonance imaging.
      OBJECTIVE: To investigate relationships between vertebral endplate remodeling,
      Modic changes, disc degeneration, and lumbar segmental mobility. SUMMARY OF
      BACKGROUND DATA: Previous studies have shown that disc degeneration and vertebral
      endplate Modic changes are associated with differences in spinal motion, however,
      the effects of vertebral endplate morphology on lumbar segmental motion have not
      been fully investigated. METHODS: A total of 420 patients underwent kinetic
      magnetic resonance imaging of 2100 lumbar motion segments. Sagittal endplate
      shapes (concave, flat, irregular), Modic changes (types, 0-3), and disc
      degeneration (grade, I-V) were assessed along with translational and angular
      motion of vertebral segments in flexion, extension, and neutral positions.
      RESULTS: The most common findings were concave endplate shape (63.24%), type 2
      Modic change (71.79%), and grade II disc degeneration (40.33%). Flat, irregular
      endplates were more common at L1-L2, L4-L5, and L5-S1 than L2-L3 and L3-L4. Types
      1, 2, and 3 Modic changes increased in frequency according to endplate shape:
      concave less than flat less than irregular. Type 0 was observed to decrease with
      the change of endplate shape from flat to concave to irregular. Vertebral levels
      with irregular endplates had more disc generation than those with flat; levels
      with flat endplates had significantly more disc degeneration than those with
      concave. Translational motion of the lumbar segment was greatest at levels with
      irregular endplates and decreased at those with flat and then concaves endplates.
      Angular motion was least at levels with irregular endplates and increased at
      levels with flat, then concave endplates. CONCLUSION: The degree of pathogenic
      lumbar segmental motion is associated with remodeling of the sagittal endplate.
      Endplate remodeling may occur as an adaptation to restrain abnormal movement of
      the lumbar segment. LEVEL OF EVIDENCE: N/A.

PMID- 24859574
TI  - The impact of reduction of pain after lumbar spine surgery: the relationship
      between changes in pain and physical function and disability.
AB  - STUDY DESIGN: Prospective cohort study. OBJECTIVE: To examine the relationship
      between improvement in pain intensity and subsequent improvement in physical
      function and disability during the first 12 months after lumbar spine surgery.
      SUMMARY OF BACKGROUND DATA: Little is known about how reduction of pain intensity
      after surgery may predict improvements in physical function and disability.
      METHODS: We prospectively enrolled 260 individuals undergoing elective surgery
      for degenerative lumbar spine conditions from August 2005 through August 2011.
      Preoperative and postoperative (3, 6, and 12 mo) assessment tools were numeric
      pain rating scale, Short Form 12 version 2 physical component score (physical
      function), and Oswestry Disability Index (disability). Changes were defined using
      minimum clinically important differences. The association between improvement in
      pain intensity and subsequent improvement in physical function and disability
      during the first 12 postoperative months was assessed using standard regression
      methods. Significance was set at a P value less than 0.05. RESULTS:
      Preoperatively, mean pain intensity was 5.2 (standard deviation, 2.4), physical
      function was 27.9 (standard deviation, 9.2), and disability was 40.1% (standard
      deviation, 16.8%). Pain intensity had improved in 164 (63.1%) patients by 3 and 6
      months and in 184 (70.8%) by 12 months. Patients with improvement in pain
      postoperatively were more likely to have subsequent improvement in physical
      function (odds ratio, 2.11; 95% confidence interval, 1.10-3.16) during the course
      of 12 postoperative months. The association between postoperative pain reduction
      and reduced disability was similar (odds ratio, 1.61; confidence interval, 1.12
      2.33). CONCLUSION: Most patients experienced clinically important postsurgical
      reductions in pain intensity by 3 months after surgery. Those patients were more
      likely to have clinically important improvement in physical function and
      reduction in disability during the first postoperative year. LEVEL OF EVIDENCE:
      1.

PMID- 24859575
TI  - Time-dependent response of scoliotic curvature to orthotic intervention: when
      should a radiograph be obtained after putting on or taking off a spinal orthosis?
AB  - STUDY DESIGN: A prospective study; 2-group design. OBJECTIVE: This study aims to
      assess the time response of scoliotic spines to orthotic intervention using
      clinical ultrasound. SUMMARY OF BACKGROUND DATA: Patients with moderate
      adolescent idiopathic scoliosis are generally advised orthotic treatment.
      However, the time to reach maximum correction after donning spinal orthosis or
      the time to return to pretreatment curvature after doffing spinal orthosis is not
      fully understood. METHOD: Subjects were divided into 2 groups, the don-orthosis
      group and the doff-orthosis group where the time reaching maximum correction and
      the time returning to pretreatment curvature were investigated accordingly. To
      avoid excessive radiation exposure via obtaining repeated radiographs, a
      validated method of estimating Cobb angle using radiation-free clinical
      ultrasound was applied at an interval of every 30 minutes up to 180 minutes. The
      spinal flexibility (estimated from supine radiographs) and body mass index were
      collected from the subjects for analyses. RESULT: Nine female patients with
      adolescent idiopathic scoliosis were recruited. There was no immediate change in
      the Cobb angles. A change of more than 5 degrees  could be observed in both
      groups only after 30 minutes and maximum change was found at/after 120 minutes.
      In the doff-orthosis group, the subject with the lowest body mass index took the
      longest time to increase more than 5 degrees  after doffing spinal orthosis. In
      the don-orthosis group, the subject with the highest body mass index took the
      longest time to achieve curve correction more than 5 degrees . CONCLUSION: This
      investigation demonstrated that there is a time lag between application of spinal
      orthosis and its effect on scoliotic curvature. This is likely due to the low
      stiff and viscoelastic properties of the spine. The clinical relevance of this
      study is that for patients with scoliosis undergoing orthotic treatment,
      radiograph should not be obtained within 2 hours of putting on or taking off
      spinal orthosis because it may not show the maximum effect. LEVEL OF EVIDENCE: 4.

PMID- 24859576
TI  - The relationship of lumbar multifidus muscle morphology to previous, current, and
      future low back pain: a 9-year population-based prospective cohort study.
AB  - STUDY DESIGN: Population based prospective cohort study. OBJECTIVE: We explored
      the cross-sectional relationships between lumbar multifidus (LM) intramuscular
      adipose tissue (IMAT) infiltration and low back pain (LBP) at 3 successive time
      points and investigated the role of IMAT in predicting the occurrence of LBP
      after 5 and 9 years. SUMMARY OF BACKGROUND DATA: Although LBP is a major source
      of disease burden, the biological determinants of LBP are poorly understood.
      METHODS: Participants were 40-year-old adults randomly sampled from a Danish
      population and followed up at 45 and 49 years of age. At each time point,
      participants underwent magnetic resonance imaging and reported ever having had
      LBP, LBP in the previous year, nontrivial LBP in the previous year, or a history
      of pain radiating into the legs. Pixel intensity and frequencies from T1-weighted
      magnetic resonance images identified the greatest proportion of LM IMAT at the L4
      and L5 spinal levels. IMAT infiltration was categorized as normal/mild, moderate,
      or severe based on tertile divisions. Associations were explored with crude and
      adjusted odds ratios (aORs) from logistic regression models. Model covariates
      included sex, body mass index, and occupational and leisure time physical
      activity. RESULTS: A total of 401 participants were enrolled, with 331 (83%) and
      286 (71%) participants followed up at 5 and 9 years, respectively. The cross
      sectional analyses demonstrated that at the age of 40 years, participants with
      severe IMAT infiltration demonstrated increased odds of ever experiencing LBP
      (aOR [95% confidence interval, 95% CI] = 3.16 [1.45-6.89]), nontrivial LBP (aOR
      [95% CI] = 2.82 [1.36-5.81]), LBP in the past year (aOR [95% CI] = 1.95 [1.07
      3.53]), and leg pain (aOR [95% CI] = 2.08 [1.19-3.62]). There were no consistent
      cross-sectional associations between LBP/leg pain and LM IMAT at 45 or 49 years
      of age and LM IMAT did not predict future LBP or leg pain. CONCLUSION: The
      relationship between LM IMAT and LBP/leg pain is inconsistent and may be modified
      by age. LEVEL OF EVIDENCE: N/A.

PMID- 24859577
TI  - Cost analysis of incidental durotomy in spine surgery.
AB  - STUDY DESIGN: Retrospective database analysis. OBJECTIVE: To characterize the
      consequences of an incidental durotomy with regard to perioperative complications
      and total hospital costs. SUMMARY OF BACKGROUND DATA: There is a paucity of data
      regarding how an incidental durotomy and its associated complications may relate
      to total hospital costs. METHODS: The Nationwide Inpatient Sample database was
      queried from 2008 to 2011. Patients who underwent cervical or lumbar
      decompression and/or fusion procedures were identified, stratified by approach,
      and separated into cohorts based on a documented intraoperative incidental
      durotomy. Patient demographics, comorbidities (Charlson Comorbidity Index),
      length of hospital stay, perioperative outcomes, and costs were assessed.
      Analysis of covariance and multivariate linear regression were used to assess the
      adjusted mean costs of hospitalization as a function of durotomy. RESULTS: The
      incidental durotomy rate in cervical and lumbar spine surgery is 0.4% and 2.9%,
      respectively. Patients with an incidental durotomy incurred a longer
      hospitalization and a greater incidence of perioperative complications including
      hematoma and neurological injury (P < 0.001). Regression analysis demonstrated
      that a cervical durotomy and its postoperative sequelae contributed an additional
      adjusted $7638 (95% confidence interval, 6489-8787; P < 0.001) to the total
      hospital costs. Similarly, lumbar durotomy contributed an additional adjusted
      $2412 (95% confidence interval, 1920-2902; P < 0.001) to the total hospital
      costs. The approach-specific procedural groups demonstrated similar discrepancies
      in the mean total hospital costs as a function of durotomy. CONCLUSION: This
      analysis of the Nationwide Inpatient Sample database demonstrates that incidental
      durotomies increase hospital resource utilization and costs. In addition, it
      seems that a cervical durotomy and its associated complications carry a greater
      financial burden than a lumbar durotomy. Further studies are warranted to
      investigate the long-term financial implications of incidental durotomies in
      spine surgery and to reduce the costs associated with this complication. LEVEL OF
      EVIDENCE: 3.

PMID- 24859578
TI  - Incidence and cost of treating axis fractures in the United States from 2000 to
      2010.
AB  - STUDY DESIGN: Retrospective database analysis. OBJECTIVE: To examine the
      incidence of hospitalization, treatment, and cost of caring for patients with
      axis (C2) fractures. SUMMARY OF BACKGROUND DATA: The incidence of C2 fractures in
      the elderly seems to be increasing, however, a comprehensive analysis of the
      incidence, treatment, and cost of treating C2 fractures has not been previously
      reported. METHODS: The Nationwide Inpatient Sample from 2000 to 2010 was used to
      identify patients with C2 fracture without neurological injury (International
      Classification of Disease, Ninth Revision, Clinical Modification code 805.02).
      Examined variables included age, International Classification of Disease, Ninth
      Revision, Clinical Modification injury severity score, comorbidities, mortality,
      hospital length of stay, treatments, and total inpatient hospitalization charge.
      Charges were adjusted for inflation to 2010 US dollars as well as for cost-to
      charge ratios. RESULTS: In total, 31,129 patients with C2 fracture were
      identified. From 2000 to 2010 the incidence of C2 fracture hospitalization
      increased in all age groups (P < 0.0001). The most rapid increase was in patients
      older than 84 years, who experienced a 3-fold increase from 3.18 to 9.77
      hospitalizations per 10,000 individuals per year (P < 0.0001). From 2000 to 2010,
      the rate of halo vest placement decreased from 25.2% to 10.4% (P < 0.0001),
      whereas the rate of surgical intervention increased from 13.1% to 16.5% (P =
      0.029). For nonoperatively treated patients, the mean hospitalization charge per
      patient increased from $39,346 in 2000 to $63,222 in 2010, and for surgically
      treated patients, it increased from $70,784 in 2000 to $133,064 in 2010 (P <
      0.0001). During the decade, the estimated charges for annual inpatient care for
      patients with C2 fracture in the United States increased 4.7-fold from
      $334,138,919 to $1,577,254,958 (P < 0.0001). CONCLUSION: The incidence of C2
      fracture hospitalizations increased dramatically from 2000 to 2010, with the most
      rapid increase in the elderly represented by a greater than 3-fold increase for
      patients older than 84 years. The inpatient charges for treating C2 fractures
      have risen faster than the increased incidence, with a 4.7-fold increase in
      hospital charges resulting in estimated annual charges of more than $1.5 billion
      in 2010. LEVEL OF EVIDENCE: 3.

PMID- 24859579
TI  - Change in morphology of intramedullary T2-weighted increased signal intensity
      after anterior decompressive surgery for cervical spondylotic myelopathy.
AB  - STUDY DESIGN: Retrospective study. OBJECTIVE: To study the change in morphology
      of T2-weighted (T2W) increased signal intensity (ISI) and its association with
      functional outcome after central corpectomy for cervical spondylotic myelopathy
      (CSM) and ossified posterior longitudinal ligament (OPLL). SUMMARY OF BACKGROUND
      DATA: There are limited data on change in T2W ISI morphology after anterior
      decompressive surgery. It is unclear whether change in T2W ISI carries prognostic
      significance in patients with CSM/OPLL. METHODS: We reviewed patients who
      underwent central corpectomy for CSM/OPLL between 1996 and 2010, and underwent a
      follow-up magnetic resonance imaging (MRI) at 6 months or later postoperatively.
      T2W ISI on sagittal images was classified as type 0 no ISI; type 1, predominantly
      (>50%) faint with an indistinct border; and type 2, predominantly (>50%) intense
      with a sharp border. The length of T2W ISI and the presence of T1-weighted
      hypointensity were also recorded on preoperative and follow-up images. Functional
      outcomes as measured by the Nurick grade were correlated with change in
      morphology of MR signal changes. RESULTS: Sixty-four patients (60 males, mean age
      = 50 +/- 1.1 yr) were reviewed. The mean follow-up duration was 29 +/- 3.5
      months. The majority of patients (71.9%) had no change in the type of ISI at
      follow-up. The type of ISI improved in 13 patients (20.3%), and worsened in 5
      patients (7.8%). The mean length of ISI was 26.2 +/- 3.4 mm preoperatively and
      13.7 +/- 1.8 mm at follow-up in 53 patients (P = 0.002). Change in ISI grade or
      length was not associated with change in Nurick grade at follow-up (P = 0.74, P =
      0.5). CONCLUSION: The type of T2W ISI does not change, but the length of T2W ISI
      decreases for the majority of patients undergoing anterior cervical decompression
      for CSM/OPLL. In our series, change in morphology of T2W ISI did not correlate
      with functional outcome as measured by Nurick grade. LEVEL OF EVIDENCE: 4.

PMID- 24859580
TI  - Analysis of 3-dimensional course of the intra-axial vertebral artery for C2
      pedicle screw trajectory: a computed tomographic study.
AB  - STUDY DESIGN: A retrospective radiological study. OBJECTIVE: To analyze the
      course of intra-axial vertebral artery (IAVA) and evaluate the relationship
      between the 3-dimensional (3D) courses for IAVA with respect to safe trajectory
      for C2 pedicle screw (C2PS). SUMMARY OF BACKGROUND DATA: The VA at the level of
      C2 has a distinct 3D course. The traditional concept of "high riding (HR)" VA was
      based on sagittal plane but does not provide all the 3D course of IAVA for safe
      C2PS placement. However, 3D course of IAVA has not been previously analyzed.
      METHODS: Three-dimensional, vascular-enhanced computed tomographic scans on the
      cervical spine of 100 patients, 200 IAVA (male to female ratio = 50:50; mean age,
      58.4 yr) were analyzed. (1) The arterial parameters including (1) "medial
      shifting (MS)" (A: lateral, B: neutral, C: medial to C3 transverse foramen [TF])
      and (2) "HR" (0: below C2TF, 1 within C2TF, 2: above C2TF) of IAVA was measured.
      (2) The bony parameters including pedicle diameter, medial convergence angle, and
      sagittal angle of C2PS were measured. Correlation between the arterial and bony
      parameters, differences between sex, laterality, dominance of VA, and age were
      analyzed. RESULTS: MS (grade A, 37.5%; B, 37%; and C, 25.5%) and HR (grade 0 in
      34%, 1 in 42%, and 2 in 24%) showed significant correlation with each other (P <
      0.001). The main patterns of IAVA were A-0 (26%), B-1 (26.5%), and C-2 (18.5%).
      Higher grade of MS and HR showed significantly smaller pedicle diameter, larger
      medial convergence angle, and smaller sagittal angle (P < 0.001). Female sex and
      older age are factors that showed significantly higher grade of MS and HR (P <
      0.001). CONCLUSION: Tortuosity of IAVA was greater in the female sex and it also
      increased with aging. The different IAVA courses significantly influenced the
      pedicle diameter and the safe trajectory for C2PS; therefore, these factors
      should be considered before planning C2 pedicle screw placement. LEVEL OF
      EVIDENCE: 3.

PMID- 24859581
TI  - Blood loss during posterior spinal fusion for adolescent idiopathic scoliosis.
AB  - STUDY DESIGN: Retrospective uncontrolled case series. OBJECTIVE: The purpose of
      this study was to determine the association, if any, between intraoperative blood
      loss and need for transfusion with the use of periapical (Ponte) osteotomies, as
      well as other patient and surgical variables among patients with adolescent
      idiopathic scoliosis (AIS) undergoing posterior spinal instrumentation and
      fusion. SUMMARY OF BACKGROUND DATA: Blood loss during posterior spinal fusion for
      AIS can be substantial. Numerous techniques are used to minimize intraoperative
      blood loss and the need for allogeneic transfusion. However, it is unclear which
      patient and surgeon variables affect blood loss most significantly. METHODS: A
      review was conducted on consecutive patients with AIS who had undergone posterior
      spinal fusion from July 1997 to February 2013 by a single primary surgeon at 1
      institution. The relationship of estimated blood loss, normalized blood loss
      (normalized blood loss = estimated blood loss/number of levels fused/patient's
      weight in kilograms), autologous blood retrieved, and allogeneic transfusion
      received with various patient- and procedure-related variables were analyzed.
      RESULTS: Estimated blood loss, normalized blood loss, and autologous blood
      retrieved were higher in patients who underwent periapical Ponte osteotomies (n =
      38) (P < 0.0001, P < 0.001, P < 0.01, respectively). The mean major curve
      correction was 64% in patients without osteotomies, and 65% in patients with
      osteotomies (P = 0.81). All patients who underwent osteotomies (38/38) received
      allogeneic transfusion versus 26% (19/73) of those without osteotomies (P <
      0.001). The likelihood of transfusion correlated with increasing number of
      osteotomies and a lower preoperative hemoglobin level (odds ratio, 3.34; P =
      0.003; and odds ratio, 0.51; P = 0.02, respectively). CONCLUSION: In patients
      with AIS undergoing posterior spinal fusion with instrumentation, performing
      periapical osteotomies increased all measures of intraoperative blood loss and
      need for transfusion without substantially improving major curve correction. As
      expected, a lower preoperative hemoglobin level was observed in patients who
      received a blood transfusion after posterior instrumentation and fusion. LEVEL OF
      EVIDENCE: 4.

PMID- 24859582
TI  - C7-T1 anterior closing wedge bone-disc-bone osteotomy for the treatment of
      cervical hyperlordosis in muscular dystrophy: a new technique for correction of a
      rare deformity.
AB  - STUDY DESIGN: A new surgical technique of cervical closing wedge osteotomy to
      correct an extension deformity of the cervical spine in patients with muscular
      dystrophy presenting clinically with debilitating hyperlordosis is described, and
      3 cases are reported. OBJECTIVE: To describe a new surgical technique with
      emphasis on the clinical results and the effect of osteotomy on sagittal balance,
      gaze angle, and spinopelvic parameters. SUMMARY OF BACKGROUND DATA: Previous
      reports of cervical osteotomy essentially have described opening wedge (extension
      osteotomy) for correction of severe flexion deformities. To the authors'
      knowledge, C7-T1 closing wedge osteotomy to correct hyperextension deformity due
      to muscular dystrophy in the cervical spine has not been described previously.
      METHODS: Three male patients aged 16, 16, and 21 years presented with cervical
      hyperlordosis due to Becker muscular dystrophy. There was upward deviation of
      forward gaze in all patients. Anterior closing wedge (bone-disc-bone) osteotomy
      of C7-T1 was performed followed with a posterior release correction and
      instrumented stabilization. The chin-brow angle was visualized with the aid of
      fluoroscopy during the operation. After closure and posterior fixation, patient
      was turned supine again and the osteotomy site was grafted and fixed with a plate
      to further strengthen the construct and to prevent any translation. RESULTS: The
      gaze angles and both sitting and standing postures of the patients markedly
      improved. There was documented fusion at the osteotomy sites. The patients were
      free of complaints at the last follow-up. CONCLUSION: Bone-disc-bone closing
      wedge osteotomy done at C7-T1 level is a technically demanding procedure but
      results in significant acute clinical and radiological improvement in patients
      with hyperextension deformity of the cervical spine. LEVEL OF EVIDENCE: 4.

PMID- 24859583
TI  - Risk factors for dural tears in the cervical spine.
AB  - STUDY DESIGN: Retrospective review of prospective database. OBJECTIVE: To
      investigate the incidence of cervical dural tears (DTs), risk factors for
      occurrence and failure of treatment, and the effect on clinical outcomes. SUMMARY
      OF BACKGROUND DATA: Only 1 study has specifically investigated the impact of
      cervical DTs. METHODS: Cervical spine surgical procedures performed by the senior
      author (K.D.R.) at Washington University from 1995-2012 were evaluated.
      Demographic data, surgical history, operative data, and complications were
      recorded prospectively, and retrospectively reviewed. Intraoperative treatment of
      DTs was noted. Treatment failure was defined by reoperation or delayed lumbar
      drain placement. Patients who sustained a dural tear (DT group) were compared
      with those who did not sustain a dural tear (No-DT group) to identify risk
      factors. Comparison between successful and failed treatments was used to identify
      risk factors for treatment failure. RESULTS: A total of 3848 cervical surgical
      procedures were performed, with 38 occurrences (1.0%) of DT. Risk factors for DT
      were: older age (P < 0.01), rheumatoid arthritis (relative risk [RR] = 3.1, 95%
      confidence interval [CI] = 1.0-9.8), ossification of the posterior longitudinal
      ligament (RR = 19.2, 95% CI = 10.4-35.6), cervical deformity (RR = 3.3, 95% CI =
      1.6-6.6), longer operative time (P = 0.01), greater number of surgical levels (P
      < 0.01), worse preoperative neurological status (P < 0.01), and performance of a
      corpectomy (RR = 2.1, 95% CI = 1.1-4.0) or revision laminectomy (RR = 20.0, 95%
      CI = 8.4-47.4). Initial treatments failed in 12 cases (32%) and hospital
      readmission was required for 5 patients (13%). Older age and ossification of the
      posterior longitudinal ligament were found to be risk factors for failure of the
      DT treatment. With an average follow-up of 18 months, there were no clinical
      sequelae from the DTs. CONCLUSION: In the largest series of cervical DTs
      reported, the incidence of DTs was found to be 1% and several risk factors were
      identified. Initial treatment failures occurred more often than previously
      reported. No significant clinical impact was found after successful DT treatment.
      LEVEL OF EVIDENCE: 4.

PMID- 24859584
TI  - Impact of increased body mass index on outcomes of elective spinal surgery.
AB  - STUDY DESIGN: Observational retrospective cohort study of prospectively collected
      database. OBJECTIVE: To determine whether overweight body mass index (BMI)
      influences 30-day outcomes of elective spine surgery. SUMMARY OF BACKGROUND DATA:
      Obesity is prevalent in the United States, but its impact on the outcome of
      elective spine surgery remains controversial. METHODS: We used National Surgical
      Quality Improvement Program, a prospective clinical database with proven validity
      and reproducibility consisting of 256 perioperative standardized variables from
      surgical patients at nearly 400 academic and nonacademic hospitals nationwide. We
      identified 49,314 patients who underwent elective fusion, laminectomy or both
      between 2006 and 2012. We divided patients according to BMI (kg/m2) as normal
      (18.5-24.9), preobese (25.0-29.9), obese I (30.0-34.9), obese II (35.0-39.9), and
      obese III (>=40). Relationship between increased BMI and outcome of surgery
      measured as prolonged hospitalization, complications, return to the operating
      room, discharged with continued care requirement, readmission, and death was
      determined using logistic regression before and after propensity score matching.
      RESULTS: All overweight patients (BMI >=25 kg/m2) showed increased odds of an
      adverse outcome compared with normal patients in unmatched analyses, with maximal
      effect seen in obese III group. In the propensity-matched sample, obese III
      patients continued to show increased odds for complications (odds ratio, 1.6; 95%
      confidence interval, 1.1-2.3), readmission (odds ratio, 2.3; 95% confidence
      interval, 1.1-4.9), and return to the operating room (odds ratio, 1.8; 95%
      confidence interval, 1.1-3.1). CONCLUSION: Impact of obesity on elective spine
      surgery outcome is mediated, at least in part, by comorbidities in patients with
      BMI between 25.0 and 39.9 kg/m2. However, BMI itself is an independent risk
      factor for adverse outcomes in morbidly obese patients. LEVEL OF EVIDENCE: 3.

PMID- 24859585
TI  - Pulmonary function improvement in patients with ankylosing spondylitis kyphosis
      after pedicle subtraction osteotomy.
AB  - STUDY DESIGN: A prospective clinical study. OBJECTIVE: To observe postoperative
      change in pulmonary function in patients with ankylosing spondylitis (AS)
      kyphosis after pedicle subtraction osteotomy (PSO). SUMMARY OF BACKGROUND DATA:
      The preoperative pulmonary dysfunction in patients with AS has been reported in
      several literatures, whereas few research about postoperative changes in
      pulmonary function with AS kyphosis was published. METHODS: A total of 32 (27
      males and 5 females) patients with AS were eligibly involved. Twenty-nine (25
      males and 4 females) patients completed the follow-up and 3 (2 males and 1
      females) patients were lost. Pulmonary function tests, breath-holding time (BHT),
      and full-length spine radiographs in natural standing position were followed
      postoperatively. RESULTS: The global kyphosis significantly decreased from 63.0
      degrees +/- 20.3 degrees  preoperatively to 15.3 degrees +/- 10.3 degrees 
      postoperatively and 17.1 degrees +/- 10.9 degrees  at the 2-year follow-up. The
      BHT before surgery was 32.5 +/- 10.1 s, whereas the postoperative BHT had
      increased to 43.1 +/- 8.6 s (P < 0.05). Two patients with AS underwent normal
      pulmonary function test before operation, whereas there were 19 patients at 2
      year follow-up. The clinical improvement rate was 85.2% (23/27). The percent
      predicted vital capacity had increased from 68.4% +/- 9.5% to 79.4% +/- 6.1% at 2
      year follow-up (P < 0.05). The percent-predicted forced vital capacity before PSO
      was 75.5% +/- 6.4% and it was 81.0% +/- 6.9% at 2-year follow-up (P < 0.05). The
      improved percent-predicted vital capacity and predicted forced vital capacity had
      a positive correlation with the correction of global kyphosis (r = 0.6328 and
      0.8612, respectively). CONCLUSION: The postoperative pulmonary function including
      pulmonary volume and ventilatory function in patients with AS with kyphosis had
      significantly improved at 2-year follow-up. And, the improved pulmonary function
      had a positive correlation with the kyphosis correction. LEVEL OF EVIDENCE: 3.

PMID- 24859586
TI  - Complications and mortality in cervical spine surgery: racial differences.
AB  - STUDY DESIGN: Retrospective national database analysis. OBJECTIVE: Our goal was
      to estimate racial and ethnic differences in in-hospital complication and
      mortality rates associated with cervical spine surgery. SUMMARY OF BACKGROUND
      DATA: The impact of observed racial and ethnic disparities in orthopedic spine
      care use on morbidity and mortality is not well understood. METHODS: On the basis
      of the Nationwide Inpatient Sample, there were 983,420 adult nontrauma hospital
      discharges from 2000 through 2009. In-hospital complications and mortality were
      the outcome variables. The primary independent variable was race/ethnicity
      (defined as non-Hispanic white [white], non-Hispanic black [black], and
      Hispanic). Covariates were age, sex, household income, insurance status,
      geographical location, hospital volume, and comorbidities. Multivariable
      regression models were used to determine the association between race/ethnicity
      and in-hospital complication and mortality. Significance was set at a P value
      less than 0.05. RESULTS: The overall rates of an in-hospital complication or
      mortality were 4.09% and 0.42%, respectively. There were no differences in the
      rates of in-hospital complications or mortality between Hispanics and Caucasians.
      Compared with Caucasians, African Americans had higher odds of experiencing an in
      hospital complication (odds ratio, 1.37; 95% confidence interval, 1.27-1.48) and
      higher odds of dying during hospitalization (odds ratio, 1.59; 95% confidence
      interval, 1.30-1.96). CONCLUSION: Although there were no differences between
      Caucasians and Hispanics, African Americans had significantly higher rates of in
      hospital complications and mortality associated with cervical spine surgery than
      did Caucasians. These differences persisted after adjusting for known risk
      factors for complications and mortality. LEVEL OF EVIDENCE: 3.

PMID- 24859587
TI  - Low lumbar fractures: does thoracolumbar injury classification and severity score
      work?
AB  - STUDY DESIGN: Case series. OBJECTIVE: To investigate if the thoracolumbar injury
      classification and severity score (TLICS) system is effective in evaluating low
      lumbar injuries. SUMMARY OF BACKGROUND DATA: The TLICS classification has been
      used by spine traumatologists since its introduction in 2006. The classification
      is predictable and consistent when dealing with thoracolumbar injuries. It is not
      known if the classification is effective in dealing with low lumbar injuries that
      tend to behave differently than thoracolumbar injuries. TLICS is yet to be
      clinically validated. There are no reports of its use for low lumbar injuries
      alone. METHODS: For this case series, 20 low lumbar injuries were graded using
      the TLICS system by 15 fellowship-trained orthopedic spine and neurosurgeons.
      Interobserver reliability was graded using kappa values. The reviewers were also
      asked 4 clinical questions regarding diagnosis and treatment of these injuries.
      RESULTS: When using the TLICS system for low lumbar injuries, there was "fair"
      reliability among the reviewers. Concerning the final TLICS score, there was 28%
      agreement with a kappa of 0.245. Concerning fracture morphology, there was 58%
      agreement with a kappa value of 0.394. When evaluating the posterior ligamentous
      complex, there was 56% agreement with a kappa value of 0.328. The reviewers did
      agree consistently on determining the patient's neurological status. The data
      showed 94% agreement with a kappa of 0.818. When looking at L3 injuries by
      themselves, the reliability of TLICS improved significantly. CONCLUSION: The
      authors think that there are factors involved in treating low lumbar injuries
      that are not inclusive to the TLICS system. Overall, there was only "fair"
      reliability for low lumbar injuries. The maintenance of lordosis and global
      sagittal alignment is paramount when dealing with low lumbar injuries and not
      considered in TLICS. L3 injuries tend to behave like thoracolumbar injuries but
      there is a wide variation in classification between L4-L5 and thoracolumbar
      injuries. LEVEL OF EVIDENCE: 4.

PMID- 24859588
TI  - Does patient-reported insomnia improve in response to interdisciplinary
      functional restoration for chronic disabling occupational musculoskeletal
      disorders?
AB  - STUDY DESIGN: An analysis of prospectively collected data. OBJECTIVE: To evaluate
      how patient-reported insomnia, in patients with chronic disabling occupational
      musculoskeletal disorders (CDOMDs), responds to a functional restoration program
      (FRP), and to investigate the relationships among insomnia, psychosocial factors,
      medication use, and post-FRP socioeconomic outcomes. SUMMARY OF BACKGROUND DATA:
      Insomnia is commonly reported by patients with chronic pain. METHODS: A
      consecutive sample of 262 patients with predominant chronic spinal pain was
      assessed with the insomnia severity index (ISI) at program admission and
      discharge. Groups were formed on the basis of the ISI total scores, from no
      clinically significant insomnia to severe clinical insomnia (SCI). Patient
      reported psychosocial measures were administered, medication information was
      collected, and ISI discharge score categories were compared with 1-year post-FRP
      socioeconomic outcomes. The Wilcoxon signed rank, repeated measures ANOVAs,
      ANOVAs and chi tests were performed. RESULTS: The degree of clinical insomnia at
      admission significantly predicted program completion, P < 0.001. Mean ISI scores
      improved from admission (M = 17.2) to discharge (M = 10.6, P < 0.001), but a
      relatively high percentage of patients (36.6%) still reported moderate to severe
      insomnia symptoms at discharge. The prevalence of SCI decreased by 18.4%, but
      this remaining group still reported more pain, disability, and depressive
      symptoms, and demonstrated more use of opioids, sedatives, and antidepressants (P
      <= 0.01), compared with the other insomnia groups at discharge. One year later,
      only 56% of the patients with severe insomnia at discharge had retained work,
      whereas 71% to 93% of those with lesser sleep disturbance were still working (P <
      0.001). Those with SCI at discharge were 10.4 times less likely to be working
      than those without clinically significant insomnia. CONCLUSION: Although insomnia
      improved for the majority of patients with chronic disabling occupational
      musculoskeletal disorder, a relatively high percentage continued to report
      clinically significant insomnia at FRP discharge. Patients with SCI reported more
      pain, depression, and disability, used more medication, and had poorer work
      outcomes 1-year post-FRP. LEVEL OF EVIDENCE: 2.

PMID- 24859589
TI  - ISSLS Prize winner: Long-term follow-up suggests spinal fusion is associated with
      increased adjacent segment disc degeneration but without influence on clinical
      outcome: results of a combined follow-up from 4 randomized controlled trials.
AB  - STUDY DESIGN: Cross-sectional analysis of long-term follow-up (LTFU) data from 4
      randomized controlled trials of operative versus nonoperative treatment for
      chronic low back pain. OBJECTIVE: To examine the influence of spinal fusion on
      adjacent segment disc space height as an indicator of disc degeneration at LTFU.
      SUMMARY OF BACKGROUND DATA: There is ongoing debate as to whether adjacent
      segment disc degeneration results from the increased mechanical stress of fusion.
      METHODS: Plain standing lateral radiographs were obtained at LTFU (mean, 13 +/- 4
      yr postrandomization) in 229 of 464 (49%) patients randomized to surgery and 140
      of 303 (46%), to nonoperative care. Disc space height and posteroanterior
      displacement were measured for each lumbar segment using a validated computer
      assisted distortion compensated roentgen analysis technique. Values were reported
      in units of standard deviations above or below age and sex-adjusted normal
      values. Patient-rated outcomes included the Oswestry Disability Index and pain
      scales. RESULTS: Radiographs were usable in 355 of 369 (96%) patients (259 fusion
      and 96 nonoperative treatment). Both treatment groups showed significantly lower
      values for disc space height of the adjacent segment than norm values. There was
      a significant difference between treatment groups for the disc space height of
      the cranial adjacent segment (in both as-treated and intention-to-treat
      analyses). The mean treatment effect of fusion on adjacent segment disc space
      height was -0.44 SDs (95% CI, -0.77 to -0.11; P = 0.01; as-treated analysis);
      there was no group difference for posteroanterior displacement (0.18 SDs, 95%
      confidence interval, -0.28 to 0.64, P = 0.45). Adjacent level disc space height
      and posteroanterior displacement were not correlated with Oswestry Disability
      Index or pain scores at LTFU (r = 0.010-0.05; P > 0.33). CONCLUSION: Fusion was
      associated with lower disc space height at the adjacent segment after an average
      of 13 years of FU. The reduced disc space height had no influence on patient self
      rated outcomes (pain or disability). LEVEL OF EVIDENCE: 2.

PMID- 24859590
TI  - Patients with adult spinal deformity treated operatively report greater baseline
      pain and disability than patients treated nonoperatively; however, deformities
      differ between age groups.
AB  - STUDY DESIGN: Multicenter, prospective analysis of consecutive patients with
      adult spinal deformity (ASD). OBJECTIVE: Identify age-related radiographical
      parameters associated with poor health-related quality of life (HRQOL) and
      treatment preferences for ASD. SUMMARY OF BACKGROUND DATA: Patients with ASD
      report discrepant severities of disability. Understanding age-associated
      differences for reported disability and treatment preferences may improve ASD
      evaluation and treatment. METHODS: Baseline demographic, radiographical, and
      HRQOL values were evaluated in a multicenter, prospective cohort of consecutive
      patients with ASD. INCLUSION CRITERIA: ASD, age more than 18 years, and no prior
      spine surgery. Patients were grouped into those treated operatively (OP) or
      nonoperatively (NON) and stratified into 3 age groups: G1, 50 years or less; G2,
      50 to 65 years; G3, 65 years or more. HRQOL measures included Scoliosis Research
      Society-22r questionnaire, Oswestry Disability Index, and Short Form-36 Health
      Survey. RESULTS: Four hundred ninety-seven patients (OP = 156, NON = 341) with a
      mean age of 50.4 years met inclusion criteria. The OP group was older (53.3 vs.
      49.0 yr), had larger scoliosis (49.3 degrees  vs. 43.3 degrees ), larger sagittal
      vertical axis (SVA, 33.2 vs. 13.7 mm), greater pelvic incidence-lumbar lordosis
      mismatch (6.6 degrees vs. 3.1 degrees ), and worse HRQOL scores than the NON
      group, respectively (P < 0.05). Age stratification demonstrated worsening of SVA,
      spinopelvic alignment (SPA), and HRQOL scores with increasing age (P < 0.05).
      Age/treatment stratification demonstrated that younger OP had greater scoliosis
      than NON (G1OP = 49.9 degrees vs. G1NON = 42.2 degrees ; G2OP = 56 degrees vs.
      G2NON = 47.2 degrees ; P < 0.05) but similar SPA as NON. Older OP had similar
      scoliosis, but larger SVA than NON (G3OP = 100.6 vs. G3NON = 66.4 mm; P < 0.05).
      OP in all age groups reported worse HRQOL than NON (P < 0.05). CONCLUSION: Poor
      HRQOL uniformly determined operative treatment for ASD. Spinal deformities
      differed between age groups. Younger OP had larger scoliosis but similar SPA and
      SVA than NON. Older OP had similar scoliosis but worse SVA than NON. Age
      associated differences for poor HRQOL must be considered when evaluating patients
      with ASD. LEVEL OF EVIDENCE: 2.

PMID- 24859591
TI  - Flagellar motility contributes to the invasion and survival of Aeromonas
      hydrophila in Anguilla japonica macrophages.
AB  - The interaction between pathogenic bacteria and the host phagocytes is
      complicated. It is generally believed that only obligate intracellular pathogens
      can invade and survive in host phagocytes. In this study, we revealed that the
      pathogenic Aeromonas hydrophila B11 can also invade and survive in the
      macrophages of its host Anguilla japonica in vitro. To further investigate the
      mechanisms of A. hydrophila invasion and survival in host macrophages, a mini
      Tn10 transposon mutagenesis system was used to generate an insertion mutant
      library by cell conjugation between the donor Escherichia coli Sm10 (pLOFKm) and
      the recipient A. hydrophila B11. Out of 465 individual colonies, 13 mutants
      impaired in survival within macrophages were selected, and the mutant BM116 was
      the most seriously impaired strain. Molecular analysis showed that an ORF of
      approximately 1335 bp (GenBank accession numbers JQ974982) of the mutant BM116
      was inserted by mini-Tn10. This ORF putatively encodes a deduced 445 amino acids
      protein that displays the highest identity (99.6%) with the flagellar hook
      protein FlgE of A. hydrophila subsp. hydrophila ATCC 7966. The biological
      characteristics of the wild-type B11, the mutant B116 and the complemented strain
      were investigated. The results reveal that the flagella of the mutant BM116 was
      absent and that these mutant bacteria exhibited defective motility, adhesion, and
      invasion and survival in host macrophages when compared with the wild type and
      the complemented strain. These findings indicate that flgE is required for
      flagellum biogenesis in A. hydrophila and that flagellar motility is required for
      A. hydrophila invasion and survival in the macrophages of its host. Our findings
      provide an important new understanding of the nonintracellular pathogenic
      bacteria invasion and survival in host phagocytes and the interactions between
      the pathogens and their host.

PMID- 24859592
TI  - Immune responses of prophenoloxidase in the mud crab Scylla paramamosain against
      Vibrio alginolyticus infection: in vivo and in vitro gene silencing evidence.
AB  - Phenoloxidase (PO) plays an important role in arthropod melanization. In the
      present study, a proPO gene was obtained from the mud crab Scylla paramamosain,
      then we localized the proPO mRNA in hemocytes and detected the expression of
      proPO after bacterial challenge. In vivo and in vitro gene silencing mediated by
      dsRNA was also used to investigate the function of proPO in innate immune. The
      full-length of the proPO cDNA was 2600 bp and the predicted ORF encoded a protein
      of 673 amino acids with a predicted molecular mass of 77.3 kDa. The deduced amino
      acid and the main functional domain of proPO shared a high similarity to the mud
      crab Scylla serrata. In situ hybridization assay showed that the proPO mRNA was
      localized in the granular and semi-granular cells. The expression level of proPO
      in hemocytes showed a clear time-dependent pattern during the 96 h course after
      stimulated by Vibrio alginolyticus. In this study, high expression levels were
      observed at 3, 12, 24 and 48 h, respectively and the highest expression level was
      observed at 12 h, and this suggested that proPO was induced by bacteria and
      involved in immune response. In vivo proPO and GFP dsRNA treatment experiments
      showed that, proPO mRNA transcript was reduced to 39%, but the PO activity showed
      no significant difference (P > 0.05). Results indicated that the expression of
      proPO could be inhibited by dsRNA, and the enzyme activity may be influenced by
      incomplete knockdown of proPO, or hemocyanin, and other proPO isoforms as well.
      In vitro proPO-silenced experiments showed that the levels of proPO were
      decreased by 36%, 64% and 77% at 8, 16 and 32 h, respectively. Meanwhile, the
      quantity of bacteria was significantly larger in proPO dsRNA treatment than that
      in control at 3 h, calculated by 4,6-diamino-2-phenylindole staining (P < 0.01).
      These data demonstrated that the proPO gene plays an important role in the
      control of systemic bacterial infections and could help us to elucidate the
      defense role of the proPO-activating system in crabs. In addition, in vitro gene
      silencing operation mediated by dsRNA was expected to be a new tool for
      investigating the function of genes in crustaceans in the case of lacking cell
      line.

PMID- 24859593
TI  - The first molluscan acute phase serum amyloid A (A-SAA) identified from oyster
      Crassostrea hongkongensis: molecular cloning and functional characterization.
AB  - Serum amyloid A (SAA), a major evolutionarily conserved acute-phase protein,
      participates in many biological processes in eukaryotic cells, including innate
      immunity. However, little information regarding the relationship between SAA and
      innate immunity in mollusks is currently available. In this report, the first
      bivalve SAA (referred to as ChSAA) gene was identified and characterized from the
      Hong Kong oyster Crassostrea hongkongensis. Its full-length cDNA is 623 bp,
      including a 5'-UTR of 147 bp, a 3'-UTR of 56 bp containing a poly(A) tail and an
      open reading frame (ORF) of 420 bp that encodes a polypeptide of 139 amino acids.
      The predicted amino acid sequence of ChSAA comprises characteristic motifs of the
      SAA family, including a typical signal peptide and a conserved SAA domain.
      Comparison and phylogenetic analyses suggested that ChSAA shares a high identity
      to known acute-phase SAA proteins (A-SAAs). In addition, quantitative real-time
      PCR analysis revealed that ChSAA is constitutively expressed in all tissues
      examined, with the highest expression level in the mantle, and that its
      expression was acutely and significantly up-regulated in hemocytes following
      challenge by Vibrio alginolyticus (G(-)), Staphylococcus haemolyticus (G(+)) or
      Saccharomyces cerevisiae (fungus). Furthermore, over-expression of ChSAA via
      transfection with a ChSAA expression vector led to significantly increased NF
      kappaB activity in HEK293T cells. These results suggest that ChSAA is likely to
      constitute a member of the A-SAA family involved in anti-pathogen responses in C.
      hongkongensis.

PMID- 24859594
TI  - Lack of a contact requirement for direct antibacterial activity of lymphocyte
      subpopulations in ginbuna crucian carp.
AB  - Cytotoxic T lymphocytes (CTL) recognize and kill cells infected with viruses,
      intracellular bacteria and tumors with MHC restriction and antigen specificity.
      In addition to these activities, recent studies in mammals have suggested that
      CTL can exhibit direct microbicidal activity. In our previous study we documented
      direct antibacterial activity of CD4(+) T cells and sIgM(+) cells as well as
      CD8alpha(+) T cells from immunized fish. However, we also found weak non-specific
      killing activity of lymphocytes against bacteria. In the present study we further
      analyzed the weak killing activity of lymphocytes, increasing the effector cell
      to target bacteria ratio from 10:1 to 10(3):1. Sensitized and non-sensitized
      effector lymphocytes (CD8alpha(+), CD4(+) and sIgM(+)) separated by MACS were
      incubated with target bacteria. CD8alpha(+) T cells from Edwardsiella tarda
      immunized ginbuna crucian carp killed 98%, 100% and 70% of E. tarda,
      Streptococcus iniae and Escherichia coli, respectively. CD8alpha(+) T cells from
      non-immunized fish showed similar but slightly lower killing activity than
      sensitized cells. CD4(+) and sIgM(+) lymphocytes also showed high killing
      activity against E. tarda and S. iniae as found for CD8alpha(+) T cells, although
      the activity was lower against E. coli. Supernatants from all three types of
      lymphocytes showed microbicidal activity, although the activity was lower than
      that evoked by effector lymphocytes. Furthermore, the presence of a membrane
      between effectors and targets did not affect the killing activity. The present
      results suggest that both sensitized and non-sensitized lymphocytes non
      specifically killed target bacteria without the need of contact. The major
      difference between the present and previous experiments is the E:T ratio. We
      suspect that there are two different mechanisms in the direct bacterial killing
      by lymphocytes in ginbuna.

PMID- 24859595
TI  - Changing patterns of antimicrobial susceptibility of invasive pneumococcal
      diseases after introduction of pneumococcal conjugate vaccine.

PMID- 24859596
TI  - Thermal ablation techniques: a curative treatment of bone metastases in selected
      patients?
AB  - INTRODUCTION: Thermal ablation techniques (radiofrequency-ablation/cryotherapy)
      can be indicated with a curative intent. The success rate and prognostic factors
      for complete treatment were analysed. MATERIAL/METHODS: The medical records of
      all patients who had undergone curatively intended thermal ablation of bone
      metastases between September 2001 and February 2012 were retrospectively
      analysed. The goal was to achieve complete treatment of all bone metastases in
      patients with oligometastatic disease (group 1) or only of bone metastases that
      could potentially lead to skeletal-related events in patients with a long life
      expectancy (group 2). We report the rate of complete treatment according to
      patient characteristics, primary tumour site, bone metastasis characteristics,
      radiofrequency ablation/cryotherapy and the treatment group (group 1/group 2).
      RESULTS: Eighty-nine consecutive patients had undergone curatively intended
      thermal ablation of 122 bone metastases. The median follow-up was 22.8 months
      [IQR = 12.2-44.4]. In the intent-to-treat analysis, the 1-year complete treatment
      rate was 67% (95%CI: 50%-76%). In the multivariate analysis the favourable
      prognostic factors for complete local treatment were oligometastatic status (p =
      0.02), metachronous (p = 0.004) and small-sized (p = 0.001) bone metastases,
      without cortical bone erosion (p = 0.01) or neurological structures in the
      vicinity (p = 0.002). CONCLUSION: Thermal ablation should be included in the
      therapeutic arsenal for the cure of bone metastases. KEY POINTS: * Thermal
      ablation techniques are currently performed to palliate pain caused by bone
      metastases. * In selected patients, thermal ablation can also be indicated with a
      curative intent. * Oligometastatic and/or metachronous diseases are good
      prognostic factors for local success. * Small-size (<2 cm) bone metastases and no
      cortical erosion are good prognostic factors.

PMID- 24859598
TI  - Automatic individualized contrast medium dosage during hepatic computed
      tomography by using computed tomography dose index volume (CTDI(vol)).
AB  - PURPOSE: To compare hepatic parenchymal contrast media (CM) enhancement during
      multi-detector row computed tomography (MDCT) and its correlation with volume
      pitch-corrected computed tomography dose index CTDI(vol)) and body weight (BW).
      MATERIAL AND METHODS: One hundred patients referred for standard three-phase
      thoraco-abdominal MDCT examination were enrolled. BW was measured in the CT
      suite. Forty grams of iodine was administered intravenously (iodixanol 320 mg
      I/ml at 5 ml/s or iomeprol 400 mg I/ml at 4 ml/s) followed by a 50-ml saline
      flush. CTDI(vol) presented by the CT equipment during the parenchymal examination
      was recorded. The CM enhancement of the liver was defined as the attenuation HU
      of the liver parenchyma during the hepatic parenchymal phase minus the
      attenuation in the native phase. RESULTS: Liver parenchymal enhancement was
      negatively correlated to both CTDI(vol) (r = -0.60) and BW (r = -0.64), but the
      difference in correlation between those two was not significant. CONCLUSION:
      CTDI(vol) may replace BW when adjusting CM doses to body size. This makes it
      potentially feasible to automatically individualize CM dosage by CT. KEY POINTS:
      * CTDI vol is related to liver CM enhancement in the parenchymal phase. * CTDI
      vol provides comparable information to body weight (BW). * CTDI vol may be used
      when automatically adjusting CM dose for patient size.

PMID- 24859597
TI  - Anatomical variations in the origins of the celiac axis and the superior
      mesenteric artery: MDCT angiographic findings and their probable embryological
      mechanisms.
AB  - OBJECTIVES: To identify the spectrum and prevalence of anatomical variations in
      the origin of the celiac axis (CA), the superior mesenteric artery (SMA) and
      their major branches by using multidetector computed tomographic (MDCT)
      angiography. METHODS: A retrospective evaluation was carried out on 1,500
      abdominal MDCT angiography images. The aortic origins of the CA, the SMA and
      their major branch patterns were investigated. RESULTS: Normal aortic origins of
      CA and SMA were noted in 1,347 (89.8%) patients. Seven types of CA and SMA origin
      variants were identified in 153 (10.2%) patients. The three most common
      variations were hepatomesenteric trunk (67 patients, 4.47%), celiomesenteric
      trunk (CMT) (51 patients, 3.4%) and splenomesenteric trunk (18 patients, 1.2%).
      An evaluation of CMT was classified as long (34 patients, 66.7%) or short (17
      patients, 33.3%) subtypes, compared with the length of the common trunk. Further
      CMT classification was based on the origin of the left gastric artery: subtype I,
      26 patients (53.1%); subtype II, 5 patients (10.2%); subtype III, 15 patients
      (30.6%); subtype IV, 3 patients (6.1%). CONCLUSIONS: Dislocation interruption,
      incomplete interruption and persistence of the longitudinal anastomosis could be
      the embryological mechanisms of the variant origins of the CA, the SMA and their
      major branches. KEY POINTS: * Aortic origins of CA, SMA and their major branches
      were investigated. * Celiomesenteric trunk includes several different subtypes
      and configurations. * Probable embryological mechanisms of origin variants in
      these observed arteries were discussed. * Origin variants in these observed
      arteries have wide-ranging health implications.

PMID- 24859599
TI  - microRNA-25 promotes osteosarcoma cell proliferation by targeting the cell-cycle
      inhibitor p27.
AB  - An increasing body of evidence indicates that microRNAs (miRNAs), a class of
      small non-coding RNAs, are often aberrantly expressed in human osteosarcoma. This
      study aimed to investigate the effects of miR-25 and to identify its potential
      target genes in osteosarcoma (OS) cells. First, the expression of miR-25 was
      detected by reverse transcription-quantitative polymerase chain reaction (RT
      qPCR), which revealed a significant upregulation of miR-25 in osteosarcoma
      tissues compared to the adjacent healthy tissues. To investigate the role of miR
      25 in osteosarcoma cell proliferation, the miR-25 precursor was next transfected
      into Saos-2 and U2OS cells. Overexpression of miR-25 promoted cell proliferation
      in vitro and tumor growth in a xenograft mouse model. In addition, our results
      revealed that the protein expression of p27, a cell-cycle inhibitor, is
      negatively regulated by miR-25. Restoring the p27 level in miR-25-overexpressing
      cells reversed the enhancing effect of miR-25 on cell proliferation. Therefore,
      miR-25 may act as an onco-miRNA in osteosarcoma, which provides new perspectives
      in cancer treatment strategies based on molecular targeting. 

PMID- 24859600
TI  - Antifeedant and Antiviral Diterpenoids from the Fresh Roots of Euphorbia
      jolkinii.
AB  - ABSTRACT: The perennial herbaceous plant Euphorbia jolkinii (Euphorbiaceae) is a
      noxious weed widely distributed in the grasslands of northwestern Yunnan and has
      greatly threatened the local biodiversity. Phytochemical investigation on the
      fresh roots of E. jolkinii afforded six new diterpenoids 1, 2, 4-6, and 8,
      together with fifteen known diterpenoids. Their structures were elucidated on the
      basis of 1D and 2D NMR and other spectroscopic methods. Casbane, lathyrane,
      abietane, and ent-kaurane diterpenoids were reported from this plant for the
      first time. Selected compounds were evaluated for their antifeedant and anti-RSV
      (respiratory syncytial virus) activities. Compound 2 and ingenol (3) exhibited
      moderate antifeedant activity against a generalist insect herbivore, Spodoptera
      exigua, with EC50 values of 17.88 and 17.71 MUg/cm(2) respectively. Compound 19
      showed significant anti-RSV activity, with 50 % inhibition (IC50) value of 10.0
      MUM and selective index of 8.0. Compounds 1 and 2 were less active against RSV
      virus, both with IC50 value of 25 MUM, and with selective indices of 1.0 and 3.2
      respectively. These findings provided new evidence for the biological functions
      and utilization of the diversified diterpenoid metabolites in the roots of this
      rich but harmful plant.

PMID- 24859602
TI  - Interferon-inducible protein 205 (p205) plays a role in adipogenic
      differentiation of mouse adipose-derived stem cells.
AB  - The role of p205 in the regulation of cell growth and differentiation remains
      poorly understood. This study aimed to determine whether p205 is involved in
      adipogenesis of mouse adipose-derived stem cells (mASCs). p205 was largely
      induced in mASCs under adipogenesis in vitro. The mRNA and protein levels of p205
      reached a maximum at day 4, and decreased at days 6 and 8. p205 localized almost
      exclusively in the nucleus of undifferentiated cells, but also translocated to
      the cytoplasm in intermediately and terminally differentiated cells. Although
      p205 suppression impaired mASC adipogenesis, its overexpression did not enhance
      the differentiation process. p205 co-localized with, and bound directly to,
      C/EBPbeta and C/EBPalpha at day 4. Knockdown of p205 lowered the amount of p205
      interacting with C/EBPbeta or C/EBPalpha, further downregulating the
      transcription activities of C/EBPalpha and PPARgamma. This suggests the
      importance of these transcription factors in the role of p205 in mASC
      adipogenesis. 

PMID- 24859601
TI  - Synthesis and anticancer activity of new flavonoid analogs and inconsistencies in
      assays related to proliferation and viability measurements.
AB  - Flavonoids have been studied intensely for their ability to act as anti
      carcinogenic, anti-inflammatory, anti-viral and anti-aging agents and are often
      marketed as supplements related to their anti-inflammatory activity. Previous
      studies have primarily focused on the effects of polar natural flavonoids. We
      examined the activity of novel hydrophobic and lipophilic flavonols against human
      DU-145 and PC-3 prostate cancer cell lines. All flavonol analogs were more active
      than the naturally occurring flavonols quercetin, kaempferol, kaempferide and
      galangin. The most potent analogs were 6.5-fold more active against DU-145 and PC
      3 cells than quercetin and fell within the biologically relevant concentration
      range (low micromolar). We also evaluated the potential toxic effects of flavonol
      analogs on normal cells, an assessment that has frequently been ignored when
      studying the anticancer effects of flavonoids. During these analyses, we
      discovered that various metabolic and DNA staining assays were unreliable methods
      for assessing cell viability of flavonoids. Flavonoids reduce colorimetric dyes
      such as MTT and Alamar Blue in the absence of cells. We showed that flavonol
      treated prostate cancer cells were stained less intensely with crystal violet
      than untreated cells at non-toxic concentrations. The trypan blue exclusion assay
      was selected as a reliable alternative for measuring cell viability. 

PMID- 24859604
TI  - Epigenetic regulation of Progesterone Receptor isoforms: from classical models to
      the sexual brain.
AB  - Progesterone Receptor is a member of the nuclear receptor superfamily, which
      regulates several functions in both reproductive and non-reproductive tissues.
      Progesterone Receptor gene encodes for two main isoforms, A and B, and contains
      two specific promoters with their respective transcription start sites. The mRNA
      expression of both isoforms is mainly regulated by estrogens and specifically via
      the Estrogen Receptor Alpha, in a context specific manner. Furthermore, it has
      been reported in extensive physiological and pathological models that
      Progesterone Receptor isoforms regulation is related to the epigenetic state of
      their respective promoters. Epigenetic regulation of Progesterone Receptor
      isoforms in the brain is a recent and scarcely explored field in neurosciences.
      This review focuses on the epigenetic mechanisms involved in Progesterone
      Receptor regulation, emphasizing the implications for the sexual brain. Future
      directions for research about this important field are also discussed. 

PMID- 24859603
TI  - AG-690/11026014, a novel PARP-1 inhibitor, protects cardiomyocytes from AngII
      induced hypertrophy.
AB  - Poly(ADP-ribose) polymerase-1 (PARP-1) enzyme, as a sensor of DNA damage, could
      convert nicotinamide adenine dinucleotide (NAD) into long poly(ADP-ribose) chains
      and regulate many cellular processes, including DNA repair, gene transcription,
      cell survival and chromatin remodeling. However, excessive activation of PARP-1
      depletes its substrate NAD and leads to cell death. Mounting evidences have shown
      that PARP-1 overactivation plays a pivotal role in the pathogenesis of cardiac
      hypertrophy and heart failure. In present study, a novel PARP-1 inhibitor AG
      690/11026014 (6014) was identified based on virtual screening and validated by
      bioassay. Our results further showed that 6014 prevented the cardiomyocytes from
      AngII-induced hypertrophy, accompanying attenuation of the mRNA and protein
      expressions of atrial natriuretic factor (ANF) and brain natriuretic peptide
      (BNP), and reduce in the cell surface area. Additionally, 6014 reversed the
      depletion ofcellular NAD and SIRT6 deacetylase activity induced by AngII in
      cardiomyocytes. These observations suggest that anti-hypertrophic effect of 6014
      might be partially attributed to the rescue of NAD depletion and subsequent
      restoring of SIRT6 activity by inhibition of PARP-1. Moreover, 6014 attenuated
      the generation of oxidative stress via suppression of NADPH oxidase 2 and 4,
      which might probably contribute to the inhibition of PARP-1. 

PMID- 24859606
TI  - Introduction to the special issue on neuroimaging in neuropharmacology.

PMID- 24859605
TI  - Effects of methoxsalen, a CYP2A5/6 inhibitor, on nicotine dependence behaviors in
      mice.
AB  - Metabolism of nicotine to inactive cotinine by hepatic enzyme CYP2A6 is the
      principal pathway by which active nicotine is removed from circulation. We
      therefore hypothesized that inhibition of mouse CYP2A5, the ortolog of human
      CYP2A6, by methoxsalen (8-methoxypsoralen) alter dependence-related behaviors of
      nicotine in the mouse. Conditioned place preference (CPP) test was used to assess
      the appetitive reward-like properties and precipitated nicotine withdrawal to
      assess physical (somatic and hyperalgesia) and affective (anxiety-related
      behaviors) measures. The nicotine plasma levels were also measured with or
      without methoxsalen pretreatment. Methoxsalen (15 and 30 mg/kg,
      intraperitoneally) pretreatment enhanced nicotine-induced preference in mice
      (p<0.05). However, there was a lack of enhancement of nicotine in the CPP test
      after the highest dose of the CYP-2A5 inhibitor. Similarly to the CPP results,
      repeated administration of methoxsalen increased the intensity of mecamylamine
      precipitated withdrawal signs. The potentiation of nicotine preference and
      withdrawal intensity by methoxsalen was accompanied by significant increase in
      nicotine plasma levels in mice (p<0.05). Finally, methoxsalen enhanced the
      ability of a very low dose of nicotine (0.05 mg/kg) to reverse withdrawal signs
      in mice undergoing spontaneous withdrawal after chronic nicotine infusion
      (p<0.05). In conclusion, inhibition of nicotine metabolism by methoxsalen alters
      the behavioral effects of nicotine in the mouse. Combining CYP2A6 inhibitors with
      low dose nicotine replacement therapies may have a beneficial role in smoking
      cessation because it will decrease the drug elimination rate and maintain plasma
      and brain nicotine levels.

PMID- 24859607
TI  - Glycyrrhizin inhibits traumatic brain injury by reducing HMGB1-RAGE interaction.
AB  - Glycyrrhizin (GL) is a major constituent of licorice root and has been suggested
      to inhibit the release of high mobility group box-1 (HMGB1), a protein considered
      representative of damage-associated molecular patterns. We found that GL bound
      HMGB1 but not RAGE with a moderate equilibrium dissociation constant value based
      on surface plasmon resonance analysis. This complex formation prevented HMGB1
      from binding to RAGE in vitro. The effects of glycyrrhizin on traumatic brain
      injury (TBI) induced by fluid percussion were examined in rats or mice in the
      present study. GL was administered intravenously after TBI. Treatment of rats
      with GL dose-dependently suppressed the increase in BBB permeability and
      impairment of motor functions, in association with the inhibition of HMGB1
      translocation in neurons in injured sites. The beneficial effects of GL on motor
      and cognitive functions persisted for 7 days after injury. The expression of TNF
      alpha, IL-1beta and IL-6 in injured sites was completely inhibited by GL
      treatment. In RAGE-/- mice, the effects of GL were not observed. These results
      suggested that GL may be a novel therapeutic agent for TBI through its
      interference with HMGB1 and RAGE interaction. 

PMID- 24859608
TI  - The neurotoxin domoate causes long-lasting inhibition of the kainate receptor
      GluK5 subunit.
AB  - Ionotropic glutamate receptors (iGluRs) are responsible for fast excitatory
      neurotransmission in the mammalian brain, and are critical regulators of neuronal
      activity and synaptic plasticity. The three main types of iGluRs (AMPA, NMDA, and
      kainate receptors) are composed of distinct subunit populations. The tetrameric
      kainate receptors can be assembled from a combination of five different types of
      subunits (GluK1-GluK5). GluK1-3 subunits are able to produce functional homomeric
      receptors, while GluK4-5 are obligate heteromers, and must assemble with a GluK1
      3 subunit. The neurotoxin domoate is widely used as an agonist at kainate-type
      receptors because it produces a less desensitizing response compared to
      glutamate. We have identified an additional, subunit-dependent action of domoate
      at recombinant kainate receptors. When applied to heteromeric GluK2/K5 receptors,
      domoate generates a small, long-lasting, tonic current. In addition, brief
      exposure to domoate inhibits the GluK5 subunit, preventing its activation by
      other agonists for several minutes. These characteristics are not associated with
      the GluK1, K2, or K4 subunits and can be prevented by a mutation in GluK5 that
      reduces agonist binding affinity. The results also show that the domoate-bound,
      GluK2/K5 heteromeric receptors can be fully activated by agonists acting through
      the GluK2 subunit, suggesting that the subunits within the tetramer can function
      independently to open the ion channel, and that the domoate-bound state is not a
      desensitized or blocked conformation. This study describes new properties
      associated with domoate action at kainate receptors, and further characterizes
      the distinct roles played by different subunits in heteromeric receptors. 

PMID- 24859610
TI  - Silencing of HIF-1alpha enhances the radiation sensitivity of human glioma growth
      in vitro and in vivo.
AB  - Gliomas are the leading cause of cancer-related mortality worldwide, and the
      incidence is increasing. Because gliomas often become resistant to radiation
      treatment, it is urgent to develop novel therapeutic methods that are more
      effective and less toxic than current therapies so as to enhance patient survival
      and quality of life. Effective enhancement of radiation therapy for gliomas in
      vivo and in vitro was observed upon silencing of hypoxia-inducible factor 1alpha
      (HIF-1alpha) with RNA interference; this enhancement was related to changes in
      the cell cycle and apoptosis that were accompanied by modulation of Cdc2, cyclin
      B1, and Bcl-2 expression. Our data suggest that HIF-1alpha silencing combined
      with radiation therapy will increase the therapeutic efficacy of glioma treatment
      via regulation of cell cycle and apoptosis-related signaling pathways.

PMID- 24859609
TI  - The metabotropic glutamate 2/3 receptor agonist LY379268 counteracted ketamine
      and apomorphine-induced performance deficits in the object recognition task, but
      not object location task, in rats.
AB  - Experimental evidence indicates that the non competitive N-methyl-d-aspartate
      (NMDA) receptor antagonist ketamine and the mixed dopamine (DA) D1/D2 receptor
      agonist apomorphine induce schizophrenia-like symptoms in rodents, including
      cognitive deficits. Activation of Group II metabotropic glutamate 2/3 (mGlu2/3)
      receptors reduces the excessive glutamate release that is hypothesized to be
      associated with psychiatric disorders. Thus, mGlu2/3 receptor agonists may
      reverse deficits induced by excessive glutamate or DA release induced by
      administration of NMDA receptor antagonists and DA receptor agonists,
      respectively, and potentially those seen in schizophrenia. LY379268 is a
      selective mGlu2/3 receptor agonist that has shown to be effective in several
      animal models of stroke, epilepsy, and drug abuse. The present study investigated
      whether LY379268 antagonizes non-spatial and spatial recognition memory deficits
      induced by ketamine and apomorphine administration in rats. To assess the effects
      of the compounds on non-spatial and spatial recognition memory, the object
      recognition task and object location task were used. Post-training administration
      of LY379268 (1-3 mg/kg, i.p.) counteracted ketamine (3 mg/kg, i.p.) and
      apomorphine (1 mg/kg, i.p.)-induced performance deficits in the object
      recognition task. In contrast, LY379268 (1-3 mg/kg, i.p.) did not attenuate
      spatial recognition memory deficits produced by ketamine (3 mg/kg, i.p.) or
      apomorphine (1 mg/kg, i.p.) in the object location task. The present data show
      that the mGlu2/3 receptor agonist LY379268 reversed non-spatial, but not spatial,
      recognition memory deficits induced by NMDA receptor blockade or DA receptor
      agonism in rodents. Thus, such mGlu2/3 receptor agonists may be efficacious in
      reversing some memory deficits seen in schizophrenia patients. 

PMID- 24859611
TI  - Head-to head comparison of mGlu1 and mGlu5 receptor activation in chronic
      treatment of absence epilepsy in WAG/Rij rats.
AB  - Acute treatment with positive allosteric modulators (PAMs) of mGlu1 and mGlu5
      metabotropic glutamate receptors (RO0711401 and VU0360172, respectively) reduces
      the incidence of spike-and wave discharges in the WAG/Rij rat model of absence
      epilepsy. However, from the therapeutic standpoint, it was important to establish
      whether tolerance developed to the action of these drugs. We administered either
      VU0360172 (3 mg/kg, s.c.) or RO0711401 (10 mg/kg, s.c.) to WAG/Rij rats twice
      daily for ten days. VU0360172 maintained its activity during the treatment,
      whereas rats developed tolerance to RO0711401 since the 3rd day of treatment and
      were still refractory to the drug two days after treatment withdrawal. In
      response to VU0360172, expression of mGlu5 receptors increased in the thalamus of
      WAG/Rij rats after 1 day of treatment, and remained elevated afterwards.
      VU0360172 also enhanced mGlu5 receptor expression in the cortex after 8 days of
      treatment without changing the expression of mGlu1a receptors. Treatment with
      RO0711401 enhanced the expression of both mGlu1a and mGlu5 receptors in the
      thalamus and cortex of WAG/Rij rats after 3-8 days of treatment. These data were
      different from those obtained in non-epileptic rats, in which repeated injections
      of RO0711401 and VU0360172 down-regulated the expression of mGlu1a and mGlu5
      receptors. Levels of VU0360172 in the thalamus and cortex remained unaltered
      during the treatment, whereas levels of RO0711401 were reduced in the cortex at
      day 8 of treatment. These findings suggest that mGlu5 receptor PAMs are potential
      candidates for the treatment of absence epilepsy in humans. 

PMID- 24859613
TI  - The oxygen radicals involved in the toxicity induced by parthenolide in MDA-MB
      231 cells.
AB  - It has been shown that the sesquiterpene lactone parthenolide lowers the
      viability of MDA-MB-231 breast cancer cells, in correlation with oxidative
      stress. The present report examined the different radical species produced during
      parthenolide treatment and their possible role in the toxicity caused by the
      drug. Time course experiments showed that in the first phase of treatment (0-8
      h), and in particular in the first 3 h, parthenolide induced dichlorofluorescein
      (DCF) signal in a large percentage of cells, while dihydroethidium (DHE) signal
      was not stimulated. Since the effect on DCF signal was suppressed by apocynin and
      diphenyleneiodonium (DPI), two inhibitors of NADPH oxidase (NOX), we suggest that
      parthenolide rapidly stimulated NOX activity with production of superoxide anion
      (O2*-), which was converted by superoxide dismutase 1 (SOD1) into hydrogen
      peroxide (H2O2). In the second phase of treatment (8-16 h), parthenolide
      increased the number of positive cells to DHE signal. Since this event was not
      prevented by apocynin and DPI and was associated with positivity of cells to
      MitoSox Red, a fluorochrome used to detect mitochondrial production of O2*-, we
      suggest that parthenolide induced production of O2*- at the mitochondrial level
      independently by NOX activity in the second phase of treatment. Finally, in this
      phase, most cells became positive to hydroxyphenyl fluorescein (HPF) signal, a
      fluorescent probe to detect highly reactive oxygen species (hROS), such as
      hydroxyl radical and peroxynitrite. Therefore, parthenolide between 8-16 h of
      treatment induced generation of O2*- and hROS, in close correlation with a marked
      reduction in cell viability.

PMID- 24859612
TI  - William L. Woolverton: a case history in unraveling the behavioral pharmacology
      of stimulants.
AB  - Clinical findings suggest that the most promising strategy for cocaine addiction
      is a combination of indirect-acting monoamine agonists with some form of
      behavioral intervention. This approach can be traced back to preclinical
      research, some of which was conducted by William L. Woolverton. The goal of this
      brief review is to provide readers with an appreciation for the experimental
      breadth involving both behavior and pharmacology that encompassed Woolverton's
      amazing career, from the evaluation of abuse liability of drugs to the use of
      complex behavioral contingencies to better model the human condition. We begin
      with Woolverton's research using simple and complex schedules of reinforcement to
      evaluate abuse liability and how that has impacted current animal models. We also
      discuss his use of cocaine vs. food choice schedules of reinforcement as a model
      to evaluate potential medications for treating cocaine use disorders. Woolverton
      concluded that drug taking behavior was not "impulsive" and "out of control" as
      has often been proposed, but rather directly determined by the environmental
      contingencies and the context of its availability, providing a nuanced
      understanding of drug-behavior interactions. This article is part of the Special
      Issue entitled 'CNS Stimulants' 

PMID- 24859614
TI  - Oropharyngeal exercises to reduce symptoms of OSA after AT.
AB  - PURPOSE: This study evaluated the efficacy of oropharyngeal exercises in children
      with symptoms of obstructive sleep apnea syndrome (OSA) after adenotonsillectomy.
      METHODS: Polysomnographic recordings were performed before adenotonsillectomy and
      6 months after surgery. Patients with residual OSA (apnea-Hypopnea Index, AHI > 1
      and persistence of respiratory symptoms) after adenotonsillectomy were randomized
      either to a group treated with oropharyngeal exercises (group 1) or to a control
      group (group 2). A morphofunctional evaluation with Glatzel and Rosenthal tests
      was performed before and after 2 months of exercises. All the subjects were re
      evaluated after exercise through polysomnography and clinical evaluation. The
      improvement in OSA was defined by DeltaAHI: (AHI at T1 - AHI at T2)/AHI at T1 *
      100. RESULTS: Group 1 was composed of 14 subjects (mean age, 6.01 +/- 1.55) while
      group 2 was composed of 13 subjects (mean age, 5.76 +/- 0.82). The AHI was 16.79
      +/- 9.34 before adenotonsillectomy and 4.72 +/- 3.04 after surgery (p < 0.001).
      The DeltaAHI was significantly higher in group 1 (58.01 %; range from 40.51 to
      75.51 %) than in group 2 (6.96 %; range from -23.04 to 36.96 %). Morphofunctional
      evaluation demonstrated a reduction in oral breathing (p = 0.002), positive
      Glatzel test (p < 0.05), positive Rosenthal test (p < 0.05), and increased labial
      seal (p < 0.001), and lip tone (p < 0.05). CONCLUSIONS: Oropharyngeal exercises
      may be considered as complementary therapy to adenotonsillectomy to effectively
      treat pediatric OSA.

PMID- 24859615
TI  - A comprehensive process for disclosing and managing conflicts of interest on
      perceived bias at the SAGES annual meeting.
AB  - INTRODUCTION: The relationship between the Society of American Gastrointestinal
      and Endoscopic Surgeons (SAGES) and its industry partners has been longstanding,
      productive technologically, and beneficial to patient care and education. In
      order to both maintain this important relationship to honor its responsibility to
      society for increasing transparency, SAGES established a Conflict of Interest
      Task Force (CITF) and charged it with identifying and managing potential
      conflicts of interest (COI) and limiting bias at the SAGES Annual Scientific
      Meetings. The CITF developed and implemented a comprehensive process for
      reporting, evaluating, and managing COI in accordance with (and exceeding)
      Accreditation Council for Continuing Medical Education guidelines. METHODS: From
      2011 to 2013, all presenters, moderators, and session chairs received proactive
      and progressively increasing levels of education regarding the CITF rationale and
      processes and were required to disclose all relationships with commercial
      interests. Disclosures were reviewed and discussed by multiple layers of
      reviewers, including moderators, chairs, and CITF committee members with tiered,
      prescribed actions in a standardized, uniform fashion. Meeting attendees were
      surveyed anonymously after the annual meeting regarding perceived bias. The CITF
      database was then analyzed and compared to the reports of perceived bias to
      determine whether the implementation of this comprehensive process had been
      effective. RESULTS: In 2011, 68 of 484 presenters (14 %) disclosed relationships
      with commercial interests. In 2012, 173 of 523 presenters (33.5 %) disclosed
      relationships, with 49 having prior review (9.4 %), and eight required
      alteration. In 2013, 190 of 454 presenters disclosed relationships (41.9 %), with
      93 presentations receiving prior review (20.4 %), and 20 presentations were
      altered. From 2008 to 2010, the perceived bias among attendees surveyed was 4.7,
      6.2, and 4.4 %; and in 2011-2013, was 2.2, 1.2, and 1.5 %. CONCLUSION: It is
      possible to have a surgical meeting that includes participation of speakers that
      have industry relationships, and minimize perceived bias.

PMID- 24859616
TI  - The EUROpean and Chinese cardiac and renal Remote Ischemic Preconditioning Study
      (EURO-CRIPS): study design and methods.
AB  - AIMS: Contrast-induced nephropathy (CIN) and periprocedural myocardial infarction
      (PMI) represent frequent complications of percutaneous coronary intervention
      (PCI) and negatively impact subsequent length of hospitalization, costs of
      adjunctive diagnostic-therapeutic measures and mid-term cardiovascular events.
      The aim of the EURO-CRIPS trial is to test whether remote ischemic
      preconditioning (RIPC) may reduce the incidence of these complications and
      improve mid-term outcome. METHODS: This will be a double-blind, randomized,
      placebo-controlled multicentre study. Patients will be allocated 1 : 1 to RIPC or
      standard therapy if they were younger than 85 years old, with a renal clearance
      in the interval 30-60 ml/min/1.73 m and candidate to PCI for all clinical
      indications except for primary PCI in ST segment elevation myocardial infarction
      (STEMI), unstable haemodynamic presentations or ongoing severe arrhythmias.
      Incidence of CIN will be the primary end point and the amount of periprocedural
      cardiac enzyme leakage will be the secondary end point. In addition, we will
      evaluate whether the preconditioned patients will have a reduction of MACCE at 6
      months (major adverse cardiac and cerebrovascular event). CONCLUSION: The EURO
      CRIPS Study will be the first large-scale, multicentre clinical trial to test the
      role of RIPC in current clinical practice. The results of this randomized trial
      will provide important insights to optimize management strategy of patients
      undergoing PCI and to improve their outcome.

PMID- 24859617
TI  - Alterations of chemical composition, construction cost and payback time in
      needles of Masson pine (Pinus massoniana L.) trees grown under pollution.
AB  - Previous studies show that Masson pine (Pinus massoniana L.) stands grown at the
      industrially-polluted site have experienced unprecedented growth decline, but the
      causal mechanisms are poorly understood. In this study, to understand the
      mechanisms of growth decline of Mason pine strands under pollution stresses, we
      determined the reactive oxygen species levels and chemical composition of the
      current-year (C) and one-year-old (C + 1) needles, and calculated the needle
      construction costs (CCmass) of Masson pine trees grown at an industrially
      polluted site and an unpolluted remote site. Pine trees grown at the polluted
      site had significantly higher levels of hydroxyl radical and superoxide anion in
      their needles than those grown at the unpolluted site, and the former trees
      eventually exhibited needle early senescence. The contents of lipids, soluble
      phenolics and lignins in C and C + 1 needles were significantly higher at the
      polluted site than at the unpolluted site, but the total amounts of non
      construction carbohydrates were lower in non-polluted needles than in polluted
      needles. Elevated levels of the reactive oxygen species and early senescence in
      polluted needles together led to significant increases in CCmass and a longer
      payback time. We infer that the lengthened payback time and needle early
      senescence under pollution stress may reduce the Masson pine tree growth and
      consequently accelerate tree decline.

PMID- 24859618
TI  - The genetic architecture of microphthalmia, anophthalmia and coloboma.
AB  - Microphthalmia, anophthalmia and coloboma (MAC) are distinct phenotypes that
      represent a continuum of structural developmental eye defects. In severe
      bilateral cases (anophthalmia or severe microphthalmia) the genetic cause is now
      identifiable in approximately 80 percent of cases, with de novo heterozygous loss
      of-function mutations in SOX2 or OTX2 being the most common. The genetic cause of
      other forms of MAC, in particular isolated coloboma, remains unknown in the
      majority of cases. This review will focus on MAC phenotypes that are associated
      with mutation of the genes SOX2, OTX2, PAX6, STRA6, ALDH1A3, RARB, VSX2, RAX,
      FOXE3, BMP4, BMP7, GDF3, GDF6, ABCB6, ATOH7, C12orf57, TENM3 (ODZ3), and VAX1.
      Recently reported mutation of the SALL2 and YAP1 genes are discussed in brief.
      Clinical and genetic features were reviewed in a total of 283 unrelated MAC cases
      or families that were mutation-positive from these 20 genes. Both the relative
      frequency of mutations in MAC cohort screens and the level of confidence in the
      assignment of disease-causing status were evaluated for each gene. 

PMID- 24859619
TI  - Catheter-based renal sympathetic denervation: limitations to and gaps in the
      evidence.
AB  - PURPOSE OF REVIEW: Renal sympathetic nerves play a significant role in the
      development and maintenance of hypertension. Percutaneous catheter-based
      radioablation of the sympathetic nerves around the renal arteries is a true
      innovation in follow up to prior animal studies. In this opinion article, we will
      review the role of the renal sympathetic network in hypertension, and the
      evidence (or the lack of it) for renal sympathetic denervation as a treatment
      modality for human hypertension. RECENT FINDINGS: Over the last 5 years, path
      breaking research has raised the promise of a dramatically effective therapy for
      treatment of resistant hypertension in the form of renal sympathetic denervation.
      Unfortunately, on the basis of limited proof-of-concept and prospective
      observational studies, this method was widely perceived as a proven therapy for
      resistant hypertension. As we have learnt from history, only properly designed
      prospective randomized controlled trials can tell whether that is indeed the
      truth. SUMMARY: Catheter-based renal sympathetic denervation, despite the recent
      setbacks, remains a novel and innovative therapeutic intervention, which may
      still have a role to play in the treatment of carefully selected patients with
      truly resistant hypertension. Mechanistic studies designed to address the cause
      of the blood pressure response (or lack thereof) to renal denervation are the
      next logical step. However, the long-term implications of renal denervation,
      especially safety issues with respect to the lack of renal sympathetic response
      in times of physiological need, are not well understood.

PMID- 24859620
TI  - E-counseling as an emerging preventive strategy for hypertension.
AB  - PURPOSE OF REVIEW: Lifestyle counseling that includes exercise training, diet
      modification, and medication adherence is critical to hypertension management.
      This article summarizes the efficacy of lifestyle counseling interventions in
      face-to-face, telehealth, and e-counseling settings. It also discusses the
      therapeutic potential of e-counseling as a preventive strategy for hypertension.
      RECENT FINDINGS: The recent proliferation of telehealth and e-counseling programs
      increases the reach of preventive counseling for patients with cardiovascular
      disorders. Blood pressure reduction following these interventions is comparable
      to face-to-face interventions. However, the effectiveness of e-counseling varies
      depending on the design features of the core protocol. An evidence-based
      guideline needs to be established that identifies e-counseling components which
      are independently associated with blood pressure reduction. As the Internet
      becomes more sophisticated, e-counseling is demonstrating a therapeutic advantage
      in comparison with other telehealth interventions. SUMMARY: Current evidence
      supports further development of preventive e-counseling programs for
      hypertension. A pressing challenge for investigators is to specify key evidence
      based components of e-counseling that are essential to the core protocol. In
      order to achieve this goal, it will be necessary to ensure that e-counseling
      programs are also clinically organized, in order to guide patients through the
      process of initiating and sustaining therapeutic behavior change.

PMID- 24859621
TI  - Protective effect of pre-infarction angina on microvascular obstruction after
      primary percutaneous coronary intervention is blunted in humans by cardiovascular
      risk factors.
AB  - BACKGROUND: Pre-infarction angina (PIA) has been shown to reduce the
      microvascular obstruction (MVO) rate in patients with ST-segment elevation
      myocardial infarction (STEMI). We sought to evaluate the potential modulator role
      of cardiovascular risk factors (CRFs) on this protective effect. METHODS AND
      RESULTS: Two hundred patients with STEMI were enrolled. PIA was defined as
      typical chest pain within the 48 h preceding STEMI onset. Angiographic MVO was
      defined as TIMI flow grade <2 or TIMI flow 3 with myocardial blush grade <2;
      electrocardiographic (ECG) MVO was defined as ST-segment elevation resolution
      <70%. Common CRFs were collected. In the absence of hypertension, both
      angiographic and ECG MVO rates were lower in patients with PIA as compared with
      those without, whereas, in the presence of hypertension, they were similar in
      both study groups (P for interaction=0.01 and P=0.014, respectively). Among
      nonsmokers, angiographic and ECG MVO rates were lower in patients with PIA as
      compared with those without, whereas within smokers, they were similar in both
      study groups (P for interaction=0.037 and P=0.037, respectively). In the absence
      of dyslipidemia, the angiographic and ECG MVO rates were lower in patients with
      PIA as compared with those without, whereas within dyslipidemic patients, they
      were similar in both study groups (P for interaction=0.012 and P=0.04,
      respectively). CONCLUSIONS: The protective effect of PIA on MVO is blunted by
      CRFs.

PMID- 24859622
TI  - Roles of xenobiotic receptors in vascular pathophysiology.
AB  - The pregnane X receptor (PXR) and constitutive androstane receptor (CAR), 2
      closely related and liver-enriched members of the nuclear receptor superfamily,
      and aryl hydrocarbon receptor (AhR), a nonnuclear receptor transcription factor
      (TF), are major receptors/TFs regulating the expression of genes for the
      clearance and detoxification of xenobiotics. They are hence defined as
      "xenobiotic receptors". Recent studies have demonstrated that PXR, CAR and AhR
      also regulate the expression of key proteins involved in endobiotic responses
      such as the metabolic homeostasis of lipids, glucose, and bile acid, and
      inflammatory processes. It is suggested that the functions of PXR, CAR and AhR
      may be closely implicated in the pathogeneses of metabolic vascular diseases,
      such as hyperlipidemia, atherogenesis, and hypertension. Therefore, manipulation
      of the activities of these receptors may provide novel strategies for the
      treatment of vascular diseases. Here, we review the pathophysiological roles of
      PXR, CAR and AhR in the vascular system.

PMID- 24859623
TI  - Treatment thresholds for hyperglycemia in critically ill patients with and
      without diabetes.

PMID- 24859624
TI  - NHS chief berates lack of ethnic diversity at board level.

PMID- 24859625
TI  - Rise in US measles cases is blamed on unimmunized travelers.

PMID- 24859626
TI  - Most emergency attendances at hospital are appropriate, finds study.

PMID- 24859627
TI  - Regulate unhealthy food like cigarettes, campaigners urge.

PMID- 24859628
TI  - US will no longer use vaccination programs as cover for spy operations, White
      House says.

PMID- 24859629
TI  - Chemokine receptor CXCR3 ligands in bronchoalveolar lavage fluid: associations
      with radiological pattern, clinical course, and prognosis in sarcoidosis.
AB  - INTRODUCTION:  Sustained inflammation in sarcoidosis may lead to lung fibrosis.
      The activity of numerous chemokines responsible for proliferation and activity of
      T lymphocytes may play a crucial role in this process and may have predictive
      value. These include cytokines induced by interferon gamma, such as CXCL9, 10,
      and 11-ligands of chemokine receptor CXCR3. OBJECTIVES:  The aim of the study was
      to estimate the role of CXCR3 ligands in the pathogenesis of sarcoidosis and the
      predictive value of their concentrations in bronchoalveolar lavage (BAL) fluid. 
      PATIENTS AND METHODS:  CXCL9, 10, and 11 concentrations in BAL fluid were
      measured by an enzyme-linked immunosorbent assay in patients with sarcoidosis (n
      = 59) and controls (n = 34). A total of 46 patients were followed up for 24
      months to compare the results between the subgroups with complete remission and
      with chronic disease. RESULTS:  Protein-standardized CXCL11 concentrations in BAL
      fluid from patients with stage II sarcoidosis were higher than in those with
      stage I (median [interquarile range], 0.95 [0.26-2.39] vs. 0.32 [0.13-0.74]
      pg/MUg protein, P = 0.02). CXCL10 levels in BAL fluid from patients without
      Lofgren syndrome were higher compared with those the syndrome (0.69 [0.51-1.05]
      vs. 0.40 [0.27-0.70] pg/MUg protein, P = 0.05). None of these markers predicted
      the chronic course of the disease. CXCL10 levels in BAL fluid correlated with
      serum angiotensin-converting enzyme, and CXCL11 levels with parenchymal lesions
      on high-resolution computed tomography. Only nonstandardized CXC11 concentrations
      in BAL fluid were higher in sarcoidosis. CONCLUSIONS:  Our results support the
      hypothesis that cytokines CXCL9, 10, and 11 may be involved in the pathogenesis
      of chronic sarcoidosis. However, the lack of notable differences between the
      sarcoidosis and control groups, as well as the lack of associations with the
      chronic course suggest that they should not be considered as potential prognostic
      markers.  

PMID- 24859630
TI  - Cell fusion induced senescence.

PMID- 24859631
TI  - Novel stilbene-triazine symmetrical optical brighteners: synthesis and
      applications.
AB  - A series of new high light fastness, hot pressing fastness optical brighteners
      was efficiently synthesized by a three-step approach involving the successive
      replacement of the three chloro groups of 2,4,6-trichloro-1,3,5-triazine under
      different conditions of temperature and pH. Thus, 2,4,6-trichloro-1,3,5-triazine
      was treated with different anilines and the resulting dichlorotriazinyl
      intermediates (3a-I) were further condensed with 4,4-diaminostilbene-2,2'
      disulfonic acid to afford bis-monochlorotriazine (5a-I) followed by nucleophilic
      substitution with ethanolamine to furnish the final hybrid brighteners (7a-I).
      All of the newly synthesized compounds were characterized by Fourier-Transform
      Infrared (FT-IR), UV-visible absorption, NMR spectroscopy and the elemental
      analyses. The synthesized optical brighteners were also assessed for their
      efficacy as fluorescent brightening agents. 

PMID- 24859632
TI  - New spiro[benzotetraphene-fluorene] derivatives: synthesis and application in sky
      blue fluorescent host materials.
AB  - Blue light-emitting spiro[benzotetraphene-fluorene] (SBTF)-based host materials,
      3-(1-naphthyl)-10-naphthylspiro[benzo[ij]tetraphene-7,9'-fluorene] (1), 3-(2
      naphthyl)-10-naphthylspiro[benzo[ij]tetraphene-7,9'-fluorene] (2), and 3-[2-(6
      phenyl)naphthyl]-10-naphthylspiro[benzo[ij]tetraphene-7,9'-fluorene] (3) were
      designed and prepared via multi-step Suzuki coupling reactions. Introducing
      various aromatic groups into SBTF core lead to a reduction in band gap and a
      determination of the color purity and luminescence efficiency. Typical sky-blue
      fluorescent organic light emitting diodes with the configuration of ITO/N,N'-di(1
      naphthyl)-N,N'-bis[(4-diphenylamino)phenyl]-biphenyl-4,4'-diamie (60
      nm)/N,N,N',N'-tetra(1-biphenyl)-biphenyl-4,4'-diamine (30 nm)/host: dopant (30
      nm, 5%)/LG201 (electron transporting layer, 20 nm)/LiF/Al were developed using
      SBTF derivatives as a host material and p-bis(p-N,N-diphenyl-aminostyryl)benzene
      (DSA-Ph) as a sky-blue dopant material. A device obtained from three materials
      doped with DSA-Ph showed color purity of 0.148 and 0.239, a luminance efficiency
      of 7.91 cd/A, and an external quantum efficiency >4.75% at 5 V.

PMID- 24859633
TI  - Changes in the microbial community structure of filaments and floc formers in
      response to various carbon sources and feeding patterns.
AB  - Filamentous bulking is a complicated problem in wastewater treatment plants
      treating various wastewaters, leading to the deterioration of the settling
      properties and the effluent quality. This study systematically investigated long
      term effects of various carbon sources and feeding patterns on the growth of
      filamentous bacteria, in order to reveal the mechanism of filamentous bulking.
      Sludge volume index (SVI), microscopic observations, staining (Gram and Neisser
      staining), scan electron microscopic, and fluorescent in situ hybridization
      (FISH) were used to monitor the bulking and track the changes of microbial
      morphology and community structure of activated sludge in six lab-scale
      sequencing batch reactors (SBRs) fed with different carbon sources. Filamentous
      bulking was not observed in all SBRs under anoxic feeding pattern with a short
      fill time, in which SVI remained below 150 mL/g. In contrast, serious bulking
      (SVI > 500 mL/g) occurred under aerobic feeding pattern when fed with ethanol,
      propionate, acetate, and glucose, in which Thiothrix and Sphaerotilus natans
      proliferated as dominant filaments. Compared to glucose-fed reactor, relatively
      light bulking was caused in starch-fed reactor with the growth of Nostocoida
      limicola II. In addition, flocs in starch-fed reactor were more open and fluffy
      than flocs formed on readily biodegradable substrates. Finally, a framework
      integrating kinetic selection, diffusion selection, storage selection, and
      protozoa capture mechanism was proposed to explain filamentous bulking.

PMID- 24859634
TI  - In vivo single-molecule imaging of bacterial DNA replication, transcription, and
      repair.
AB  - In vivo single-molecule experiments offer new perspectives on the behaviour of
      DNA binding proteins, from the molecular level to the length scale of whole
      bacterial cells. With technological advances in instrumentation and data
      analysis, fluorescence microscopy can detect single molecules in live cells,
      opening the doors to directly follow individual proteins binding to DNA in real
      time. In this review, we describe key technical considerations for implementing
      in vivo single-molecule fluorescence microscopy. We discuss how single-molecule
      tracking and quantitative super-resolution microscopy can be adapted to extract
      DNA binding kinetics, spatial distributions, and copy numbers of proteins, as
      well as stoichiometries of protein complexes. We highlight experiments which have
      exploited these techniques to answer important questions in the field of
      bacterial gene regulation and transcription, as well as chromosome replication,
      organisation and repair. Together, these studies demonstrate how single-molecule
      imaging is transforming our understanding of DNA-binding proteins in cells. 

PMID- 24859635
TI  - Significant associations between lipoprotein(a) and corrected apolipoprotein B
      100 levels in African-Americans.
AB  - OBJECTIVES: Lipoprotein(a), Lp(a), represents an apolipoprotein (apo) B-carrying
      lipoprotein, yet the relationship between Lp(a) and apoB levels has not been
      fully explored. METHODS: We addressed the relationship between Lp(a) and apoB
      containing lipoprotein levels in 336 Caucasians and 224 African-Americans. Our
      approach takes unique molecular properties of Lp(a) as well as contribution of
      Lp(a) to the levels of these lipoproteins into account. RESULTS: Levels of total
      cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), apoB and apoB/apoA
      1 did not differ across ethnicity. African-Americans had higher levels of Lp(a)
      and high-density lipoprotein cholesterol and lower triglyceride levels compared
      to Caucasians. Lp(a) levels were correlated with levels of TC (p < 0.005), LDL-C
      (p < 0.001), apoB (p < 0.05) or apoB/apoA-1 (p < 0.05) in both ethnic groups.
      These associations remained significant only in African-Americans after
      adjustments for the contribution of Lp(a)-cholesterol or Lp(a)-apoB. Furthermore,
      taking Lp(a)-apoB into account, allele-specific apo(a) levels were significantly
      associated with apoB levels and the apoB/apoA-1 ratio in African-Americans. The
      latter associations in African-Americans remained significant for allele-specific
      apo(a) levels for smaller apo(a) sizes (<26 K4 repeats), after controlling for
      the effects of age, sex, and BMI. CONCLUSIONS: Although TC, LDL-C, and apoB
      levels were comparable between African-Americans and Caucasians, the associations
      of these parameters with Lp(a) and allele specific apo(a) levels differed between
      these two ethnic groups. In African-Americans, apoB and apoB/apoA-1 remained
      consistently and positively associated with both Lp(a) and allele-specific apo(a)
      levels after adjustments for the contribution of Lp(a)-apoB. The findings suggest
      an interethnic difference with a closer relationship between Lp(a) and apoB among
      African-Americans.

PMID- 24859636
TI  - Halogen bonds enhanced by sigma-hole and pi-hole interactions: a comparative
      study on cooperativity and competition effects between X???N and S???N
      interactions in H3N???XCN???SF2 and H 3N???XCN???SO2 complexes (X   = F, Cl, Br
      and I).
AB  - Halogen bonding, a noncovalent interaction between a halogen atom X in one
      molecule and a negative site in another, plays an important role in fields as
      diverse as molecular biology, drug design, and crystal engineering. In this work,
      the H3N???XCN???SF2 and H3N???XCN???SO2 (X  =  F, Cl, Br, I) complexes are
      theoretically investigated to find ways to enhance the halogen bond interaction.
      Cooperative effects are found when X???N and S???N bonds coexist in the same
      complex. The ab initio calculations are carried out using at the MP2/aug-cc-pVTZ
      level, through analysis of surface electrostatic potentials VS(r), interaction
      energies and the topological analysis based on the quantum theory of atoms in
      molecules. Particular attention is paid to understand the origin of the X???N and
      S???N interactions in the ternary complexes. The cooperativity between both types
      of the interaction is mainly caused by the electrostatic effects.

PMID- 24859637
TI  - Health risks associated with crude oil spill exposure.
AB  - BACKGROUND: Human exposure to crude oil spills is associated with multiple
      adverse health effects including hematopoietic, hepatic, renal, and pulmonary
      abnormalities. The purpose of this study was to assess the hematological and
      liver function indices among the subjects participating in the Gulf oil spill
      cleanup operations in comparison with the standardized normal range reference
      values. METHODS: Using medical charts, clinical data (including white blood cell
      [WBC] count, platelet count, hemoglobin, hematocrit, blood urea nitrogen [BUN]
      creatinine, alkaline phosphatase [ALP], aspartate amino transferase [AST],
      alanine amino transferase [ALT], and urinary phenol) were gathered for the
      subjects who were exposed to the Gulf oil spill and analyzed. RESULTS: A total of
      117 subjects exposed to the oil spill were included. Over 77% of subjects had WBC
      counts in the mid range (6-10 * 10(3) per MUL), while none of the subjects had
      the upper limit of the normal range (11 * 10(3) per MUL). A similar pattern was
      seen in the platelet counts and BUN levels among the oil spill-exposed subjects.
      Conversely, over 70% of the subjects had creatinine levels toward the upper limit
      of the normal range and 23% of subjects had creatinine levels above the upper
      limit of the normal range (>1.3 mg per dL). Similarly, hemoglobin and hematocrit
      levels were toward the upper limit of normal in more than two thirds of the
      subjects. AST and ALT levels above the upper limit of normal range (>40 IU per L)
      were seen in 15% and 31% of subjects, respectively. Over 80% of subjects had
      urinary phenol levels higher than detectable levels (2 mg per L). CONCLUSION: The
      results of this study support our earlier study findings in which we found that
      people who participated in oil spill cleanup activities are at risk of developing
      alterations in hematological profile and liver function.

PMID- 24859639
TI  - A twisted tale: chronic abdominal pain caused by gastric volvulus.

PMID- 24859638
TI  - Polycystic ovary syndrome: update on diagnosis and treatment.
AB  - Polycystic ovary syndrome is now a well-recognized condition affecting 6%-25% of
      reproductive-aged women, depending on the definition. Over the past 3 decades,
      research has launched it from relative medical obscurity to a condition
      increasingly recognized as common in internal medicine practices. It affects
      multiple systems, and requires a comprehensive perspective on health care for
      effective treatment. Metabolic derangements and associated complications include
      insulin resistance and diabetes, hyperlipidemia, hypertension, fatty liver,
      metabolic syndrome, and sleep apnea. Reproductive complications include oligo
      /amenorrhea, sub-fertility, endometrial hyperplasia, and cancer. Associated
      psychosocial concerns include depression and disordered eating. Additionally,
      cosmetic issues include hirsutism, androgenic alopecia, and acne. This review
      organizes this multi-system approach around the mnemonic "MY PCOS" and discusses
      evaluation and treatment options for the reproductive, cosmetic, and metabolic
      complications of this condition. 

PMID- 24859640
TI  - Maternal negative affect is associated with emotional feeding practices and
      emotional eating in young children.
AB  - BACKGROUND: Although mothers of young children frequently experience negative
      affect, little is known about the association between these symptoms and their
      children's eating behaviors. We aimed to test a model in which maternal negative
      affect would be related to maternal emotional eating which in turn would be
      associated with child emotional eating through maternal feeding practices
      (emotional and instrumental feeding) in a cross-sectional sample of mothers and
      their children. METHODS: A sample of 306 mothers (mean age = 35.0 years, SD =
      0.46) of 2-year-old children completed a survey assessing symptoms of depression,
      anxiety and stress, maternal emotional eating, maternal feeding practices, and
      child emotional eating. RESULTS: Maternal symptoms of depression, anxiety, and
      stress were correlated with maternal emotional eating (p < .001), and child
      emotional eating (p < .05). The initial model proposed was not a good fit to the
      data. Modification indices indicated that the model would be improved if a direct
      pathway was added between maternal and child emotional eating. As this model was
      theoretically plausible these changes were made. The resulting model proved a
      good fit to the data, chi2 = 17.36, p = .098, and explained 29% of the variance
      in child emotional eating. CONCLUSIONS: High levels of negative affect and
      associated emotional eating in mothers may contribute to the use of instrumental
      and emotional feeding practices. Our findings suggested that maternal negative
      affect has an indirect effect on children's emotional eating, primarily through
      mothers' own emotional eating and feeding her child to regulate the child's
      emotions.

PMID- 24859641
TI  - Improved performance and stability in quantum dot solar cells through band
      alignment engineering.
AB  - Solution processing is a promising route for the realization of low-cost, large
      area, flexible and lightweight photovoltaic devices with short energy payback
      time and high specific power. However, solar cells based on solution-processed
      organic, inorganic and hybrid materials reported thus far generally suffer from
      poor air stability, require an inert-atmosphere processing environment or
      necessitate high-temperature processing, all of which increase manufacturing
      complexities and costs. Simultaneously fulfilling the goals of high efficiency,
      low-temperature fabrication conditions and good atmospheric stability remains a
      major technical challenge, which may be addressed, as we demonstrate here, with
      the development of room-temperature solution-processed ZnO/PbS quantum dot solar
      cells. By engineering the band alignment of the quantum dot layers through the
      use of different ligand treatments, a certified efficiency of 8.55% has been
      reached. Furthermore, the performance of unencapsulated devices remains unchanged
      for over 150 days of storage in air. This material system introduces a new
      approach towards the goal of high-performance air-stable solar cells compatible
      with simple solution processes and deposition on flexible substrates. 

PMID- 24859642
TI  - A stable three-dimensional topological Dirac semimetal Cd3As2.
AB  - Three-dimensional (3D) topological Dirac semimetals (TDSs) are a recently
      proposed state of quantum matter that have attracted increasing attention in
      physics and materials science. A 3D TDS is not only a bulk analogue of graphene;
      it also exhibits non-trivial topology in its electronic structure that shares
      similarities with topological insulators. Moreover, a TDS can potentially be
      driven into other exotic phases (such as Weyl semimetals, axion insulators and
      topological superconductors), making it a unique parent compound for the study of
      these states and the phase transitions between them. Here, by performing angle
      resolved photoemission spectroscopy, we directly observe a pair of 3D Dirac
      fermions in Cd3As2, proving that it is a model 3D TDS. Compared with other 3D
      TDSs, for example, beta-cristobalite BiO2 (ref. 3) and Na3Bi (refs 4, 5), Cd3As2
      is stable and has much higher Fermi velocities. Furthermore, by in situ doping we
      have been able to tune its Fermi energy, making it a flexible platform for
      exploring exotic physical phenomena.

PMID- 24859643
TI  - Internal dynamics of a supramolecular nanofibre.
AB  - A large variety of functional self-assembled supramolecular nanostructures have
      been reported over recent decades. The experimental approach to these systems
      initially focused on the design of molecules with specific interactions that lead
      to discrete geometric structures, and more recently on the kinetics and
      mechanistic pathways of self-assembly. However, there remains a major gap in our
      understanding of the internal conformational dynamics of these systems and of the
      links between their dynamics and function. Molecular dynamics simulations have
      yielded information on the molecular fluctuations of supramolecular assemblies,
      yet experimentally it has been difficult to obtain analogous data with
      subnanometre spatial resolution. Using site-directed spin labelling and electron
      paramagnetic resonance spectroscopy, we measured the conformational dynamics of a
      self-assembled nanofibre in water through its 6.7 nm cross-section. Our
      measurements provide unique insight for the design of supramolecular functional
      materials. 

PMID- 24859644
TI  - Heavy-fermion quantum criticality and destruction of the Kondo effect in a nickel
      oxypnictide.
AB  - A quantum critical point arises at a continuous transformation between distinct
      phases of matter at zero temperature. Studies in antiferromagnetic heavy-fermion
      materials have revealed that quantum criticality has several classes, with an
      unconventional type that involves a critical destruction of the Kondo
      entanglement. To understand such varieties, it is important to extend the
      materials basis beyond the usual setting of intermetallic compounds. Here we show
      that a nickel oxypnictide, CeNiAsO, exhibits a heavy-fermion antiferromagnetic
      quantum critical point as a function of either pressure or P/As substitution. At
      the quantum critical point, non-Fermi-liquid behaviour appears, which is
      accompanied by a divergent effective carrier mass. Across the quantum critical
      point, the low-temperature Hall coefficient undergoes a rapid sign change,
      suggesting a sudden jump of the Fermi surface and a destruction of the Kondo
      effect. Our results imply that the enormous materials basis for the oxypnictides,
      which has been so crucial in the search for high-temperature superconductivity,
      will also play a vital role in the effort to establish the universality classes
      of quantum criticality in strongly correlated electron systems. 

PMID- 24859645
TI  - Occupational kneeling and squatting: development and validation of an assessment
      method combining measurements and diaries.
AB  - OBJECTIVES: As knee-straining postures such as kneeling and squatting are known
      to be risk factors for knee disorders, there is a need for effective exposure
      assessment at the workplace. Therefore, the aim of this study was to develop a
      method to capture knee-straining postures for entire work shifts by combining
      measurement techniques with the information obtained from diaries, and thus
      avoiding measuring entire work shifts. This approach was applied to various
      occupational tasks to obtain an overview of typical exposure values in current
      specific occupations. METHODS: The analyses were carried out in the field using
      an ambulatory measuring system (CUELA) to assess posture combined with one-day
      self-reported occupational diaries describing the durations of various work
      tasks. In total, 242 work shifts were measured, representing 81 typical tasks
      from 16 professions. Knee-straining postures were analysed as daily time
      intervals for five different postures. The accuracy of the method was examined by
      comparing the results to measurements of entire work shifts. RESULTS: Unsupported
      kneeling was the most widely used knee posture in our sample (median 11.4 % per
      work shift), followed by supported kneeling (3.0 %), sitting on heels (1.1 %),
      squatting (0.7 %), and crawling (0.0 %). The daily time spent in knee-straining
      postures varied considerably, both between the individual occupations, within an
      occupation (e.g. parquet layers: 0.0-88.9 %), and to some extent even within a
      single task (e.g. preparation work of floor layers (22.0 +/- 23.0 %). The applied
      measuring method for obtaining daily exposure to the knee has been proven valid
      and efficient randomly compared with whole-shift measurements (p = 0.27).
      CONCLUSIONS: The daily degree of postural exposure to the knee showed a huge
      variation within the analysed job categories and seemed to be dependent on the
      particular tasks performed. The results of this study may help to develop an
      exposure matrix with respect to occupational knee-straining postures. The tested
      combination of task-based measurement and diary information may be a promising
      option for providing a cost-effective assessment tool.

PMID- 24859646
TI  - Characterization of two paralogous StAR genes in a teleost, Nile tilapia
      (Oreochromis niloticus).
AB  - Steroidogenic acute regulatory protein (StAR) transports cholesterol, the
      substrate for steroid synthesis, to the inner membranes of mitochondria. It is
      well known that estrogen is essential for female sex
      determination/differentiation in fish. However, no reports showed that the
      conventional StAR, which was supposed to be essential for estrogen production,
      was expressed in female gonads during the critical timing of sex
      determination/differentiation. In this study, two different StAR isoforms, named
      as StAR1 and StAR2, were characterized from the gonads of Nile tilapia
      (Oreochromis niloticus). Phylogenetic and synteny analysis revealed that two StAR
      genes existed in teleosts, Xenopus and chicken indicating that the duplication
      event occurred before the divergence of teleosts and tetrapods. Real-time PCR
      revealed that StAR1 was dominantly expressed in the testis, head kidney and
      kidney; while StAR2 was expressed exclusively in the gonads. In situ
      hybridization and immunohistochemistry demonstrated that StAR1 was expressed in
      the interrenal cells of the head kidney and Leydig cells of the testis; while
      StAR2 was expressed in the Leydig cells of the testis and the interstitial cells
      of the ovary. Ontogenic analysis demonstrated that StAR2 was expressed abundantly
      from 5 days after hatching (dah) in the somatic cells in XX gonads, whereas in XY
      gonads, both StARs could be detected from 30 dah until adulthood. Intraperitoneal
      injection of human chorionic gonadotropin experiments showed that expression of
      StAR1 and 2 was significantly elevated at 8h and persisted until 24h after
      injection in the testis. Taken together, our data suggested that StAR1 is likely
      to be required for cortisol production in the head kidney, and StAR2 is probably
      involved in estrogen production during early sex differentiation in XX gonads. In
      contrast, both StARs might be required for androgen production in testes. For the
      first time, our data demonstrated that two fish StARs might be involved in
      steroidogenesis in a tissue and developmental stage dependent manner.

PMID- 24859647
TI  - Isomer-nonspecific action of dichlorodiphenyltrichloroethane on aryl hydrocarbon
      receptor and G-protein-coupled receptor 30 intracellular signaling in apoptotic
      neuronal cells.
AB  - Extended residual persistence of the pesticide dichlorodiphenyltrichloroethane
      (DDT) raises concerns about its long-term neurotoxic effects. Little is known,
      however, about DDT toxicity during the early stages of neural development. This
      study demonstrated that DDT-induced apoptosis of mouse embryonic neuronal cells
      is a caspase-9-, caspase-3-, and GSK-3beta-dependent process, which involves p,p'
      DDT-specific impairment of classical ERs. It also provided evidence for DDT
      isomer-nonspecific alterations of AhR- and GPR30-mediated intracellular
      signaling, including changes in the levels of the receptor and receptor-regulated
      mRNAs, and also changes in the protein levels of the receptors. DDT-induced
      stimulation of AhR-signaling and reduction of GPR30-signaling were verified using
      selective ligands and specific siRNAs. Co-localization of the receptors was
      demonstrated with confocal microscopy, and the presence of functional GPR30 was
      detected by electrophysiology. This study demonstrates that stimulation of AhR
      signaling and impairment of GPR30-signaling play important roles in the
      propagation of DDT-induced apoptosis during the early stages of neural
      development. 

PMID- 24859648
TI  - Assessment of the proliferative capacity of the flavanones 8-prenylnaringenin, 6
      (1.1-dimethylallyl)naringenin and naringenin in MCF-7 cells and the rat mammary
      gland.
AB  - 8-Prenylnaringenin (8-PN) and naringenin (Nar) are phytoestrogens found in food
      items and nutritional supplements, while 6-(1.1-dimethylallyl)naringenin (6-DMAN)
      is a component of an African plant. Besides their assumed beneficial effects they
      may promote mammary and endometrial cancer. We therefore assessed their
      proliferative and estrogenic potential on the mammary gland in vitro and in vivo.
      In competitive estrogen receptor (ER) ligand binding assays 8-PN displayed a high
      relative binding affinity for both ERs with a preference for ERalpha and had the
      strongest mitotic effect on MCF-7 cells among the test substances. In a three day
      exposure in young adult ovariectomized female rats 15 mg/kg 8-PN had the highest
      capacity to increase the number of terminal end buds (TEB) in the mammary gland
      and stimulated expression of proliferation markers in epithelial ductal cells,
      followed by 6-DMAN and Nar, but overall their capacity to stimulate proliferation
      was weak in comparison to 17beta-Estradiol (E2).

PMID- 24859651
TI  - Extremely late (7 years) paclitaxel-eluting stent thrombosis.

PMID- 24859649
TI  - Protein kinase C and Src family kinases mediate angiotensin II-induced protein
      kinase D activation and acute aldosterone production.
AB  - Recent evidence has shown a role for the serine/threonine protein kinase D (PKD)
      in the regulation of acute aldosterone secretion upon angiotensin II (AngII)
      stimulation. However, the mechanism by which AngII activates PKD remains unclear.
      In this study, using both pharmacological and molecular approaches, we
      demonstrate that AngII-induced PKD activation is mediated by protein kinase C
      (PKC) and Src family kinases in primary bovine adrenal glomerulosa cells and
      leads to increased aldosterone production. The pan PKC inhibitor Ro 31-8220 and
      the Src family kinase inhibitors PP2 and Src-1 inhibited both PKD activation and
      acute aldosterone production. Additionally, like the dominant-negative serine
      738/742-to-alanine PKD mutant that cannot be phosphorylated by PKC, the dominant
      negative tyrosine-463-to-phenylalanine PKD mutant, which is not phosphorylatable
      by the Src/Abl pathway, inhibited acute AngII-induced aldosterone production.
      Taken together, our results demonstrate that AngII activates PKD via a mechanism
      involving Src family kinases and PKC, to underlie increased aldosterone
      production.

PMID- 24859650
TI  - The local corticotropin-releasing hormone receptor 2 signalling pathway partly
      mediates hypoxia-induced increases in lipolysis via the cAMP-protein kinase A
      signalling pathway in white adipose tissue.
AB  - Our objective was to investigate the mechanisms by which the endogenous CRHR2 in
      white adipose tissue (WAT) regulates metabolic activities associated with
      lipogenesis and lipolysis under continuous exposure to hypoxia. We found that
      hypobaric hypoxia at a simulated altitude of 5000 m significantly reduced the
      body weight, food intake, and WAT mass of rats. Hypoxia also accelerated
      lipolysis and suppressed lipogenesis in WAT. Pretreatment with astressin 2B, a
      selective CRHR2 antagonist, partly but significantly attenuated the hypoxia
      induced reductions in body weight and WAT mass by blocking the cAMP-protein
      kinase A (PKA)-hormone-sensitive lipase (HSL)/perilipin signalling pathway.
      Astressin 2B treatment failed to attenuate hypoxia induced lipogenic inhibition.
      In conclusion, activation of endogenous WAT Ucn2/3 autocrine/paracrine pathway
      was involved in hypoxia induced lipolysis via CRHR2 - cAMP-PKA signalling
      pathway. This study provides the novel understanding of local CRHR2 signaling
      pathway playing important role in WAT loss and lipid metabolism under hypoxia.

PMID- 24859652
TI  - Percutaneous mitral commissurotomy in rheumatic mitral stenosis associated with
      cor triatriatum.
AB  - Cor triatriatum is an uncommon congenital anomaly and its coexistence with
      rheumatic mitral stenosis is rare. We report two patients with rheumatic mitral
      stenosis with associated cor triatriatum. Percutaneous mitral valvuloplasty was
      successfully performed in both cases. We describe the clinical presentation and
      discuss the technical issues related to balloon mitral valvotomy in these cases. 

PMID- 24859653
TI  - Characterization and pharmacokinetic analysis of crystalline versus amorphous
      rapamycin dry powder via pulmonary administration in rats.
AB  - The pharmacokinetics of inhaled rapamycin (RAPA) is compared for amorphous versus
      crystalline dry powder formulations. The amorphous formulation of RAPA and
      lactose (RapaLac) was prepared by thin film freezing (TFF) using lactose as the
      stabilizing agent in the weight ratio 1:1. The crystalline formulation was
      prepared by wet ball milling RAPA and lactose and posteriorly blending the
      mixture with coarse lactose (micronized RAPA/micronized lactose/coarse
      lactose=0.5:0.5:19). While both powders presented good aerosolization performance
      for lung delivery, TFF formulation exhibited better in vitro aerodynamic
      properties than the crystalline physical mixture. Single-dose 24h pharmacokinetic
      studies were conducted in Sprague-Dawley rats following inhalation of the aerosol
      mist in a nose-only inhalation exposure system. Lung deposition was higher for
      the crystalline group than for the TFF group. Despite higher pulmonary levels of
      drug that were found for the crystalline group, the systemic circulation (AUC0
      24) was higher for the amorphous group (8.6 ngh/mL) than for crystalline group
      (2.4 ngh/mL) based on a five-compartmental analysis. Lung level profiles suggest
      that TTF powder stays in the lung for the same period of time as the crystalline
      powder but it presented higher in vivo systemic bioavailability due to its
      enhanced solubility, faster dissolution rate and increased FPF at a more distal
      part of the lungs.

PMID- 24859654
TI  - Ultralow-phase-noise oscillators based on BAW resonators.
AB  - This paper presents two 2.1-GHz low-phase noise oscillators based on BAW
      resonators. Both a single-ended common base structure and a differential Colpitts
      structure have been implemented in a 0.25-MUm BiCMOS process. The detailed design
      methods including the realization, optimization, and test are reported. The
      differential Colpitts structure exhibits a phase noise 6.5 dB lower than the
      single-ended structure because of its good performance of power noise immunity.
      Comparison between the two structures is also carried out. The differential
      Colpitts structure shows a phase noise level of -87 dBc/Hz at 1-kHz offset
      frequency and a phase noise floor of -162 dBc/Hz, with an output power close to 
      6.5 dBm and a core consumption of 21.6 mW. Furthermore, with the proposed
      optimization methods, both proposed devices have achieved promising phase noise
      performance compared with state-of-the-art oscillators described in the
      literature. Finally, we briefly present the application of the proposed BAW
      oscillator to a micro-atomic clock. 

PMID- 24859655
TI  - Measurements of frequency fluctuations in aluminum nitride contour-mode
      resonators.
AB  - As part of the current drive to engineer miniaturized monolithic high-performance
      microelectromechanical-enabled oscillators, there is a need for further study of
      frequency fluctuations in microelectromechanical resonators. To this end, we
      present the measurement of frequency fluctuations for 128 aluminum nitride
      contour-mode resonators. The measurements show that fluctuations are sufficiently
      large to play an important role in oscillator performance. These results were
      obtained for the first time from vector network analyzer measurements and are
      accompanied by an analysis of the experimental setup.

PMID- 24859656
TI  - Chirped frequency transfer: a tool for synchronization and time transfer.
AB  - We propose and demonstrate the phase-stabilized transfer of a chirped frequency
      as a tool for synchronization and time transfer. Technically, this is done by
      evaluating remote measurements of the transferred, chirped frequency. The gates
      of the frequency counters, here driven by a 10-MHz oscillation derived from a
      hydrogen maser, play a role analogous to the 1-pulse per second (PPS) signals
      usually employed for time transfer. In general, for time transfer, the gates
      consequently must be related to the external clock. Synchronizing observations
      based on frequency measurements, on the other hand, only requires a stable
      oscillator driving the frequency counters. In a proof of principle, we
      demonstrate the suppression of symmetrical delays, such as the geometrical path
      delay. We transfer an optical frequency chirped by around 240 kHz/s over a fiber
      link of around 149 km. We observe an accuracy and simultaneity, as well as a
      precision (Allan deviation, 18,000 s averaging interval) of the transferred
      frequency of around 2 * 10(-19). We apply chirped frequency transfer to remote
      measurements of the synchronization between two counters' gate intervals. Here,
      we find a precision of around 200 ps at an estimated overall uncertainty of
      around 500 ps. The measurement results agree with those obtained from reference
      measurements, being well within the uncertainty. In the present setup, timing
      offsets up to 4 min can be measured unambiguously. We indicate how this range can
      be extended further.

PMID- 24859657
TI  - A fast minimum variance beamforming method using principal component analysis.
AB  - Minimum variance (MV) beamforming has been studied for improving the performance
      of a diagnostic ultrasound imaging system. However, it is not easy for the MV
      beamforming to be implemented in a real-time ultrasound imaging system because of
      the enormous amount of computation time associated with the covariance matrix
      inversion. In this paper, to address this problem, we propose a new fast MV
      beamforming method that almost optimally approximates the MV beamforming while
      reducing the computational complexity greatly through dimensionality reduction
      using principal component analysis (PCA). The principal components are estimated
      offline from pre-calculated conventional MV weights. Thus, the proposed method
      does not directly calculate the MV weights but approximates them by a linear
      combination of a few selected dominant principal components. The combinational
      weights are calculated in almost the same way as in MV beamforming, but in the
      transformed domain of beamformer input signal by the PCA, where the dimension of
      the transformed covariance matrix is identical to the number of some selected
      principal component vectors. Both computer simulation and experiment were carried
      out to verify the effectiveness of the proposed method with echo signals from
      simulation as well as phantom and in vivo experiments. It is confirmed that our
      method can reduce the dimension of the covariance matrix down to as low as 2 * 2
      while maintaining the good image quality of MV beamforming. 

PMID- 24859658
TI  - Rheology over five orders of magnitude in model hydrogels: agreement between
      strain-controlled rheometry, transient elastography, and supersonic shear wave
      imaging.
AB  - Shear wave elastography helps physicians to characterize pathologies by assessing
      biomechanical properties of soft tissues. Compared with classical rheology, these
      techniques allow the quantification of the mechanical properties of tissues in
      the frequency range of hundreds of hertz. In this paper, ultrasound elastographic
      measurements and classical rheology are compared over a frequency range spanning
      five orders of magnitude [0.01 to 1200 Hz] to characterize model gels at multiple
      scales. Hybrid hydrogels were specially synthesized to get a fine tuning of the
      material dissipative response. Strain-controlled rheology (SCR) experiments were
      performed to get the elastic moduli G" and loss moduli G" from 0.01 Hz to 10 Hz
      and were confirmed by tensile tests. Transient elastography (TE from 50 to 400
      Hz) and supersonic shear imaging (SSI from 200 to 1200 Hz) were used to
      characterize polymers at high frequency. Two different hydrogels were tested in
      the ultrasound setup with different concentration of scatterers. From low
      frequency measurements, elastic moduli were extrapolated at high frequency and a
      very good correlation was obtained between SCR and TE and between SCR and SSI (r
      = 0.92 and r = 0.95, respectively). This paper demonstrates the capability of
      shear wave elastography to accurately image rheological properties of soft
      tissues, to differentiate soft elastic domains from viscous ones. It also gives
      new insights into soft material science because it provides a rheological tool in
      a high-frequency domain complementary to conventional rheometry.

PMID- 24859659
TI  - Discrimination of breast microcalcifications using a strain-compounding technique
      with ultrasound speckle factor imaging.
AB  - The usefulness of breast ultrasound could be extended by improving the detection
      of microcalcifications by being able to detect and enhance microcalcifications
      while simultaneously eliminating hyperechoic spots (e.g., speckle noise and
      fibrocystic changes) that can be mistaken for microcalcifications (i.e., false
      microcalcifications). This study investigated the use of a strain-compounding
      technique with speckle factor (SF) imaging to analyze the degree of scatterer
      redistributions in breast tissues under strain conditions for identifying
      microcalcifications and false microcalcifications. The efficacy of the proposed
      method was tested by collecting raw data of ultrasound backscattered signals from
      26 lesions at BI-RADS category 4 or 5 with suspicious microcalcifications. The
      different strain conditions were created by applying manual compression to deform
      the breast lesion. For each region in which microcalcifications were suspected,
      estimates of the SNR of the strain-compounding B-scan images and estimates of the
      mean SF (SFavg) in the strain-compounding SF images were calculated. Compared
      with microcalcifications, the severity of speckle of the false
      microcalcifications would be easily degraded under compressive strain conditions.
      The results demonstrated that the SNR estimates in the strain-compounding B-scan
      images for microcalcifications and false microcalcifications were 5.22 +/- 1.04
      (mean +/- standard deviation) and 4.62 +/- 1.09, respectively; the corresponding
      SFavg estimates in the strain-compounding SF images were 0.47 +/- 0.10 and 0.22
      +/- 0.10 (p < 0.01). The mean area under the receiver operating characteristic
      curve using the SNR estimate was 0.71, whereas that using the SFavg estimate was
      0.94. These findings indicate that the strain-compounding SF imaging method is
      more effective at discriminating between microcalcifications and false
      microcalcifications. 

PMID- 24859660
TI  - Transcranial cavitation detection in primates during blood-brain barrier opening-
      a performance assessment study.
AB  - Focused ultrasound (FUS) has been shown promise in treating the brain locally and
      noninvasively. Transcranial passive cavitation detection (PCD) provides
      methodology for monitoring the treatment in real time, but the skull effects
      remain a major challenge for its translation to the clinic. In this study, we
      investigated the sensitivity, reliability, and limitations of PCD through primate
      (macaque and human) skulls in vitro. The results were further correlated with the
      in vivo macaque studies including the transcranial PCD calibration and real-time
      monitoring of blood-brain barrier (BBB) opening, with magnetic resonance imaging
      assessing the opening and safety. The stable cavitation doses using harmonics
      (SCDh) and ultraharmonics (SCDu), the inertial cavitation dose (ICD), and the
      cavitation SNR were quantified based on the PCD signals. Results showed that
      through the macaque skull, the pressure threshold for detecting the SCDh remained
      the same as without the skull in place, whereas it increased for the SCDu and
      ICD; through the human skull, it increased for all cavitation doses. The
      transcranial PCD was found to be reliable both in vitro and in vivo when the
      transcranial cavitation SNR exceeded the 1-dB detection limit through the in
      vitro macaque (attenuation: 4.92 dB/mm) and human (attenuation: 7.33 dB/ mm)
      skull. In addition, using long pulses enabled reliable PCD monitoring and
      facilitate BBB opening at low pressures. The in vivo results showed that the SCDh
      became detectable at pressures as low as 100 kPa; the ICD became detectable at
      250 kPa, although it could occur at lower pressures; and the SCDu became
      detectable at 700 kPa and was less reliable at lower pressures. Real-time
      monitoring of PCD was further implemented during BBB opening, with successful and
      safe opening achieved at 250 to 600 kPa in both the thalamus and the putamen. In
      conclusion, this study shows that transcranial PCD in macaques in vitro and in
      vivo, and in humans in vitro, is reliable by improving the cavitation SNR beyond
      the 1-dB detection limit. 

PMID- 24859661
TI  - Dynamic frame pairing in real-time freehand elastography.
AB  - Quasi-static ultrasound (US) elastography is now a well-established technique
      that involves acquiring US (RF/envelope) signals from an imaging plane before and
      after a small quasi-static compression to form axial strain elastograms (ASE).
      The image quality of the ASEs is a function of the applied axial strain. This
      relationship was extensively investigated and formalized in terms of strain
      filter in the literature. Most of the work in elastography formed elastograms by
      choosing pre- and post-compression frames separated by a desired compression
      strain. Although this approach is feasible in simulations and in vitro/in vivo
      experiments that involve controlled compression, it has been a challenge to do
      this during freehand compression in real time. In this work, we describe a one
      prediction-one- correction method that dynamically selects pre- and post-
      compression frames to form an elastogram, based on the applied axial strain
      level. We validate the method using controlled compression experiments on
      phantoms and compare the performance of the dynamic frame pairing method against
      successive-frame pairing method in terms of the contrast-to-noise ratio (CNRe).
      Further, we demonstrate the advantages of the new method with the help of
      freehand acquired data from phantom experiments and in vivo breast data. The
      results demonstrate that the frame-pairing identified by the dynamic method
      matched the frame pairing that was designed to yield an applied axial strain of
      ~1%. The CNRe obtained by the traditional approach varied from as low as ~5 to as
      high as ~25, depending on the choice of skip number and compression rate.
      However, the dynamic frame pairing method provided elastograms with a CNRe that
      was consistently around ~20, irrespective of the compression rate. The results
      from analysis of 22 in vivo breast data demonstrated that the dynamic pairing
      method generated elastograms such that the frame-average axial strain (FAAS) of
      each frame in the cine-loop is consistently ~1% (0.011 +/- 0.001).

PMID- 24859663
TI  - Wideband dispersion reversal of lamb waves.
AB  - Ultrasonic guided waves have been widely acknowledged as the most promising tools
      for nondestructive evaluation (NDE). However, because of the multimodal
      dispersion, the received guided modes usually overlap in both time and frequency,
      which highly complicates the mode separation and signal interpretation. The time
      reversal technique can be used to realize the time recompression of the Lamb
      waves, but because of the multimode excitation and reception, it still may not be
      able to remove the mode ambiguity and achieve the pure pulse compression. With
      the goal of overcoming this limitation, a wideband dispersion reversal (WDR)
      technique is proposed. The technique makes use of a priori knowledge of the
      guided dispersion characteristics to synthesize the corresponding dispersion
      reversal excitations, which are able to selectively excite the self-compensation
      pure mode pulse. The theoretical basis of the technique is thoroughly described.
      A two-dimensional finite-difference time-domain (2D-FDTD) method is employed to
      simulate the propagation of two fundamental Lamb modes, the symmetrical S0 and
      antisymmetrical A0 modes in a steel plate. The proposed method was verified
      through experimental investigation. Finally, the advantages and potential
      applications of the method are briefly discussed. 

PMID- 24859662
TI  - Ultrasound backscatter tensor imaging (BTI): analysis of the spatial coherence of
      ultrasonic speckle in anisotropic soft tissues.
AB  - The assessment of fiber architecture is of major interest in the progression of
      myocardial disease. Recent techniques such as magnetic resonance diffusion tensor
      imaging (MR-DTI) or ultrasound elastic tensor imaging (ETI) can derive the fiber
      directions by measuring the anisotropy of water diffusion or tissue elasticity,
      but these techniques present severe limitations in a clinical setting. In this
      study, we propose a new technique, backscatter tensor imaging (BTI), which
      enables determination of the fiber directions in skeletal muscles and myocardial
      tissues, by measuring the spatial coherence of ultrasonic speckle. We compare the
      results to ultrasound ETI. Acquisitions were performed using a linear transducer
      array connected to an ultrasonic scanner mounted on a motorized rotation device
      with angles from 0 degrees  to 355 degrees  by 5 degrees  increments to image ex
      vivo bovine skeletal muscle and porcine left ventricular myocardial samples. At
      each angle, multiple plane waves were transmitted and the backscattered echoes
      recorded. The coherence factor was measured as the ratio of coherent intensity
      over incoherent intensity of backscattered echoes. In skeletal muscle,
      maximal/minimal coherence factor was found for the probe parallel/perpendicular
      to the fibers. In myocardium, the coherence was assessed across the entire
      myocardial thickness, and the position of maxima and minima varied transmurally
      because of the complex fibers distribution. In ETI, the shear wave speed
      variation with the probe angle was found to follow the coherence variation.
      Spatial coherence can thus reveal the anisotropy of the ultrasonic speckle in
      skeletal muscle and myocardium. BTI could be used on any type of ultrasonic
      scanner with rotating phased-array probes or 2-D matrix probes for noninvasive
      evaluation of myocardial fibers. 

PMID- 24859664
TI  - Block-sparse reconstruction and imaging for Lamb wave structural health
      monitoring.
AB  - A frequently investigated paradigm for monitoring the integrity of plate-like
      structures is a spatially-distributed array of piezoelectric transducers, with
      each array element capable of both transmitting and receiving ultrasonic guided
      waves. This configuration is relatively inexpensive and allows interrogation of
      defects from multiple directions over a relatively large area. Typically, full
      sets of pairwise transducer signals are acquired by exciting one transducer at a
      time in a round-robin fashion. Many algorithms that operate on such data use
      differential signals that are created by subtracting prerecorded baseline
      signals, leaving only signal differences introduced by scatterers. Analysis
      methods such as delay-and-sum imaging operate on these signals to detect and
      locate point-like defects, but such algorithms have limited performance and
      suffer when potential scatterers have high directionality or unknown phase
      shifting behavior. Signal envelopes are commonly used to mitigate the effects of
      unknown phase shifts, but this further reduces performance. The blocksparse
      technique presented here uses a different principle to locate damage: each pixel
      is assumed to have a corresponding multidimensional linear scattering model,
      allowing any possible amplitude and phase shift for each transducer pair should a
      scatterer be present. By assuming that the differential signals are linear
      combinations of a sparse subset of these models, it is possible to split such
      signals into location-based components. Results are presented here for three
      experiments using aluminum and composite plates, each with a different type of
      scatterer. The scatterers in these images have smaller spot sizes than delay-and
      sum imaging, and the images themselves have fewer artifacts. Although a
      propagation model is required, block-sparse imaging performs well even with a
      small number of transducers or without access to dispersion curves. 

PMID- 24859665
TI  - Design and analysis of a connected broadband multi-piezoelectric-bimorph- beam
      energy harvester.
AB  - The rapid growth of remote, wireless, and microelectromechanical system (MEMS)
      devices over the past decades has motivated the development of a self-powered
      system that can replace traditional electrochemical batteries. Piezoelectric
      energy harvesters are ideal for capturing energy from mechanical vibrations in
      the ambient environment. Numerous studies have been made of this application of
      piezoelectric energy conversion; however, the narrow frequency operation band has
      limited its application to generate useful power. In this paper, a broadband
      energy harvester with an array/matrix of piezoelectric bimorphs connected by
      springs has been designed and analyzed based on the 1-D piezoelectric beam
      equations. The predicted result shows that the operational frequency band can be
      enlarged significantly by carefully adjusting the small end masses, length of the
      beam and spring stiffness. An optimal selection of the load impedance to realize
      the maximum power output is discussed. The results provide an important
      foundation for future broadband energy harvester design. 

PMID- 24859666
TI  - Design of a junction for a noncontact ultrasonic transportation system.
AB  - A junction for noncontact ultrasonic transportation paths in which small objects
      can be manipulated is proposed. The junction consists of a vibrating disc and a
      reflector. The reflector is installed parallel to the vibrator to generate an
      acoustic standing wave in the cavity between the vibrating disc and the
      reflector. The resonance modes of the acoustic field in the disc cavity between
      the two plates are calculated theoretically. The distributions of the sound
      pressure amplitude and the acoustic radiation force in air are calculated using
      finite element analysis. The flexural vibration modes with one nodal circle and
      four nodal lines at 45.4 kHz and two nodal circles and three nodal lines at 58.1
      kHz are used to trap and eject small objects, respectively. The transportation
      velocity and the thrust force in the radial direction for a polystyrene particle
      with a diameter of 2 mm and a weight of 0.3 mg are 812 mm/s and 24 MUN,
      respectively. The ejection direction of the trapped object can be controlled by
      the driving condition of the vibrating disc. 

PMID- 24859668
TI  - Gas flow induced by ultrasonic cavitation bubble clouds and surface capillary
      wave.
AB  - In this paper, we report a gas flow phenomenon induced by ultrasonic water
      cavitation and capillary wave in a vibrating hollow tip and reflector system. The
      cavitation clouds generated a gas suction force and the capillary wave created
      tunnels through which the gas could go into the liquid. The gas flow rate was
      measured and compared under different conditions, including applied power, type
      of reflector, and tip-to-reflector distance. A model was proposed to explain the
      mechanisms of the gas flow and analyze the results in the experiments. 

PMID- 24859667
TI  - PMN-PT single-crystal high-frequency kerfless phased array.
AB  - This paper reports the design, fabrication, and characterization of a miniature
      high-frequency kerfless phased array prepared from a PMN-PT single crystal for
      forward-looking intravascular or endoscopic imaging applications. After lapping
      down to around 40 MUm, the PMN-PT material was utilized to fabricate 32-element
      kerfless phased arrays using micromachining techniques. The aperture size of the
      active area was only 1.0 * 1.0 mm. The measured results showed that the array had
      a center frequency of 40 MHz, a bandwidth of 34% at -6 dB with a polymer matching
      layer, and an insertion loss of 20 dB at the center frequency. Phantom images
      were acquired and compared with simulated images. The results suggest that the
      feasibility of developing a phased array mounted at the tip of a forward-looking
      intravascular catheter or endoscope. The fabricated array exhibits much higher
      sensitivity than PZT ceramic-based arrays and demonstrates that PMN-PT is well
      suited for this application.

PMID- 24859669
TI  - Investigation of polyvinylidene fluoride (PVDF) films in identifying high
      frequency vibration modes of flexible plates.
AB  - Compared with piezoelectric ceramics such as lead zirconate titanate (PZT)
      ceramics, the low density and high compliance of the PVDF films make them a more
      suitable choice in modal testing, especially for detecting high-frequency modes
      in flexible or inflatable structures. In this work, dynamic sensing performances
      of PVDF films for flexible structures in modal testing are examined, with
      considerations including the repeatability of the impact source, the accuracy of
      the sensing responses, and the influences of the nodal lines on the frequency
      spectra of the transient responses. Two flexible plates with different boundary
      conditions and thickness are considered. Experimental results, compared with FEM
      computations or theoretical predictions, demonstrate the excellent dynamic
      sensing performance of the PVDF film in modal testing applications, especially
      for identification of high-frequency modes on flexible structures. 

PMID- 24859670
TI  - Employing executive functions of perceptual and memory abilities in underweight
      and weight-restored anorexia nervosa patients.
AB  - PURPOSE: Executive functions (EF) have been widely investigated in anorexia
      nervosa (AN) revealing difficulties in various aspects. We aimed at testing the
      effects of EF on stimuli perception and its representations in memory. METHODS:
      Thirty AN underweight patients, 30 weight-restored AN patients, and 44 control
      participants, were recruited. Various EF were assessed using the Rey-Osterrieth
      Complex Figure Test, analyzed with the Boston Qualitative Scoring System.
      RESULTS: No differences were found in visuo-constructional measures in either AN
      groups compared to controls on the copy and memory stages. However, both groups
      performed significantly worse than controls on most EF variables in the copy
      stage, while in the immediate and delayed memory stages the difference was less
      substantial. CONCLUSIONS: Difficulties in EF among AN patients, current and
      weight restored, are more pronounced in the perceptual module and less so when
      employed through memory retrieval. The pattern, which is apparent after weight
      gain, suggests that there is no ameliorative effect on these difficulties.

PMID- 24859672
TI  - Is social inhibition of return due to action co-representation?
AB  - When two individuals alternate reaching responses to visual targets presented on
      a shared workspace, one individual is slower to respond to targets occupying the
      same position as their partner's previous response. This phenomenon is thought to
      be due to processes that inhibit the initiation of a movement to a location
      recently acted upon. However, two distinct forms of the inhibition account have
      been posited, one based on inhibition of an action, the other based on inhibition
      of an action and location. Furthermore, an additional recent explanation suggests
      the phenomenon is due to mechanisms that give rise to action congruency effects.
      Thus the three different theories differ in the degree to which action co
      representation plays a role in the effect. The aim of the present work was to
      examine these competing accounts. Three experiments demonstrated that when
      identical actions are made, the effect is modulated by the configuration of the
      visual stimuli acted upon and the perceptual demands of the task. In addition,
      when the co-actors perform different actions to the same target, the effect is
      still observed. These findings support the hypothesis that this particular joint
      action phenomenon is generated via social cues that induce location-based
      inhibition of return rather than being due to shared motor co-representations. 

PMID- 24859671
TI  - Management of urinary incontinence after radical prostatectomy.
AB  - In the year following a radical prostatectomy, most men recover from any initial
      urinary incontinence. Nonetheless, incontinence greatly affects a man's quality
      of life during that time, as it does for those who have persistent incontinence
      thereafter. Urological assessment should be thorough in order to ensure that no
      treatable etiology exists aside from stress incontinence. Conservative measures
      can then be applied from the earliest stages, and offer benefit for those with
      mild to moderate symptoms. Failing this, a wide variety of surgical options can
      be considered. For effective outcomes, a clinician must ensure that surgical
      decision-making is based on current evidence and patient preference, and that it
      considers possible morbidities.

PMID- 24859673
TI  - The influence of object identity on obstacle avoidance reaching behaviour.
AB  - When reaching for target objects, we hardly ever collide with other objects
      located in our working environment. Behavioural studies have demonstrated that
      the introduction of non-target objects into the workspace alters both spatial and
      temporal parameters of reaching trajectories. Previous studies have shown the
      influence of spatial object features (e.g. size and position) on obstacle
      avoidance movements. However, obstacle identity may also play a role in the
      preparation of avoidance responses as this allows prediction of possible negative
      consequences of collision based on recognition of the obstacle. In this study we
      test this hypothesis by asking participants to reach towards a target as quickly
      as possible, in the presence of an empty or full glass of water placed about half
      way between the target and the starting position, at 8 cm either left or right of
      the virtual midline. While the spatial features of full and empty glasses of
      water are the same, the consequences of collision are clearly different. Indeed,
      when there was a high chance of collision, reaching trajectories veered away more
      from filled than from empty glasses. This shows that the identity of potential
      obstacles, which allows for estimating the predicted consequences of collision,
      is taken into account during obstacle avoidance.

PMID- 24859674
TI  - Expression and purification of an active cecropin-like recombinant protein
      against multidrug resistance Escherichia coli.
AB  - Lucilin is a 36 residue cecropin antimicrobial peptide identified as a partial
      genetic sequence in Lucilia sericata maggots. The antimicrobial spectrum and
      toxicity profile of Lucilin is unknown. We first report the expression of Lucilin
      as an active recombinant fusion protein with a cysteine protease domain (CPD)
      tag. The fusion protein, GWLK-Lucilin-CPD-His8, showed maximum overexpression in
      Escherichia coli BL21 cells after 12h induction with 0.5mM IPTG (isopropyl beta-d
      thiogalactoside) and growth conditions were 37  degrees C and 150 rpm shaking.
      The fusion protein was expressed as a soluble form and was purified by Ni-IMAC.
      The purified protein was active against E. coli ATCC 35218 with a MIC of 0.68
      MUM, and a clinical isolate of E. coli with extended spectrum beta-lactamase
      (ESBL) with a MIC of 0.8 MUM. The recombinant GWLK-Lucilin-CPD-His8 was not toxic
      against human erythrocytes or Vero cells with a therapeutic index >63. The
      results suggest that GWLK-Lucilin-CPD-His8 represents a potential candidate for
      therapy against multidrug resistant Gram-negative bacteria.

PMID- 24859675
TI  - Ubiquitin fusion constructs allow the expression and purification of multi-KOW
      domain complexes of the Saccharomyces cerevisiae transcription elongation factor
      Spt4/5.
AB  - Spt4/5 is a hetero-dimeric transcription elongation factor that can both inhibit
      and promote transcription elongation by RNA polymerase II (RNAPII). However,
      Spt4/5's mechanism of action remains elusive. Spt5 is an essential protein and
      the only universally-conserved RNAP-associated transcription elongation factor.
      The protein contains multiple Kyrpides, Ouzounis and Woese (KOW) domains. These
      domains, in other proteins, are thought to bind RNA although there is little
      direct evidence in the literature to support such a function in Spt5. This could
      be due, at least in part, to difficulties in expressing and purifying recombinant
      Spt5. When expressed in Escherichia coli (E. coli), Spt5 is innately insoluble.
      Here we report a new approach for the successful expression and purification of
      milligram quantities of three different multi-KOW domain complexes of
      Saccharomyces cerevisiae Spt4/5 for use in future functional studies. Using the
      E. coli strain Rosetta2 (DE3) we have developed strategies for co-expression of
      Spt4 and multi-KOW domain Spt5 complexes from the bi-cistronic pET-Duet vector.
      In a second strategy, Spt4/5 was expressed via co-transformation of Spt4 in the
      vector pET-M11 with Spt5 ubiquitin fusion constructs in the vector pHUE. We
      characterized the multi-KOW domain Spt4/5 complexes by Western blot, limited
      proteolysis, circular dichroism, SDS-PAGE and size exclusion chromatography
      multiangle light scattering and found that the proteins are folded with a
      Spt4:Spt5 hetero-dimeric stoichiometry of 1:1. These expression constructs
      encompass a larger region of Spt5 than has previously been reported, and will
      provide the opportunity to elucidate the biological function of the multi-KOW
      containing Spt5. 

PMID- 24859677
TI  - Production of stable isotope labelled lipase Lip2 from Yarrowia lipolytica for
      NMR: investigation of several expression systems.
AB  - Extracellular lipase Lip2 from Yarrowia lipolytica is a promising biocatalyst
      with unusual structural features, as indicated by X-ray crystallography. These
      features comprise a mobile domain called the lid that controls access to the
      catalytic site. Conformational rearrangements of the lid have been suggested to
      regulate lipase enzymatic activities. We used nuclear magnetic resonance to
      investigate the dynamics of Lip2 by exploring four expression systems,
      Escherichia coli, cell-free, Pichia pastoris and Y. lipolytica to produce
      uniformly labelled enzyme. The expression of Lip2 was assessed by determining its
      specific activity and measuring (15)N-(1)H HSQC spectra. Y. lipolytica turned out
      to be the most efficient expression system. Here, we report the first use of Y.
      lipolytica as an expression host for the production of uniform stable isotopic
      labelled protein for further structural and dynamics studies using NMR. 

PMID- 24859676
TI  - Thermophilic esterase from Thermomyces lanuginosus: molecular cloning, functional
      expression and biochemical characterization.
AB  - A novel esterase encoding gene, tle, was cloned from the thermophilic fungus
      Thermomyces lanuginosus DSM 10635. The tle had an open reading frame of 945bp
      encoding TLE of 314 amino acids with a theoretical molecular mass of 34.5kDa. The
      putative catalytic triad of TLE was consisted of Ser151, His279, and Asp249. TLE
      was heterologously expressed in Escherichia coli in biologically active form and
      purified to homogeneity. Several biochemical properties of TLE were studied:
      Among the tested p-nitrophenol esters, TLE showed the highest hydrolytic activity
      with p-nitrophenyl butyrate (C4) and exhibited the maximum activity at 60 degrees
      C and pH 8.5. The enzyme was stable at temperatures below 60 degrees C and
      retained 53% of the maximum activity after treatment at 70 degrees C for 60min.
      Esterase activity was notably enhanced by addition of Ca(2+) and Ba(2+),
      respectively. Furthermore, TLE showed high enantioselectivity (E=95) in the
      kinetic resolution of 2-carboxyethyl-3-cyano-5-methylhexanoic acid ethyl ester
      (CNDE), which produce a valuable chiral intermediate-(3S)-2-carboxyethyl-3-cyano
      5-methylhexanoic acid for Pregabalin. These unique properties of the esterase
      indicate that TLE is a potential candidate for industrial application.

PMID- 24859678
TI  - Assessment of the microbiological quality of groundwater in three regions of the
      Valencian Community (Spain).
AB  - Urban groundwater development was traditionally constrained by concerns about its
      quality. This study was conducted in the regions of La Ribera Alta and Ribera
      Baja and La Plana de Requena-Utiel of the Valencian Community (Valencia, Spain)
      where population density, demand for drinking water and agricultural activities
      are high. Groundwater bodies (GWBs) are regarded as management areas within each
      territory, and were used to establish protection policies. This study analyzed
      eleven GWBs. We used two databases with microbiological measurements from 154
      wells over a 7-year period (2004-2011), risk factors and groundwater information.
      Wells were grouped according to frequency of microbiological contamination using
      E. coli measurements, category <1, or wells with low-frequency microbiological
      contamination and high-frequency wells or category 1-100, according to World
      Health Organization (WHO) quality criteria of drinking water. Of all wells,
      18.12% showed high-frequency microbiological contamination with a majority
      distribution in the Ribera Alta region (26.98%, p < 0.001). No significant
      differences were found between the two risk categories for flow, static level,
      well depth and distance from population centres. This paper reveals that the
      vulnerability classes established by the Geological and Mining Institute of Spain
      (IGME) do not match the microbiological results, and that only eight wells with
      high-frequency contamination coincide with the high vulnerability areas. 

PMID- 24859679
TI  - A qualitative investigation of adolescents' perceived mechanisms of change from a
      universal school-based depression prevention program.
AB  - A recent meta-analysis provides evidence supporting the universal application of
      school-based prevention programs for adolescent depression. The mechanisms
      underlying such successful interventions, however, are largely unknown. We report
      on a qualitative analysis of 109 Grade 9 students' beliefs about what they gained
      from an evidence-based depression prevention intervention, the Resourceful
      Adolescent Program (RAP-A). Fifty-four percent of interviewees articulated at
      least one specific example of program benefit. A thematic analysis of responses
      revealed two major themes, improved interpersonal relationships and improved self
      regulation, both stronger than originally assumed. A more minor theme also
      emerged-more helpful cognitions. It is postulated that both improved
      interpersonal relationships and improved self-regulation are likely to enhance
      one another, and more helpful cognitions may express its contribution through
      enhanced self-regulation. These findings broaden our understanding of the impact
      of depression prevention programs, beginning to illuminate how such programs
      benefit participants. 

PMID- 24859681
TI  - Eyes underground: regression of visual protein networks in subterranean mammals.
AB  - Regressive evolution involves the degeneration of formerly useful structures in a
      lineage over time, and may be accompanied by the molecular decay of phenotype
      specific genes. The mammalian eye has repeatedly undergone degeneration in taxa
      that occupy dim-light environments including subterranean habitats. Here we
      assess whether a decrease in the amount of light that reaches the retina is
      associated with increased regression of retinal genes, whether the
      phototransduction and visual cycle pathways degrade in a predictable pattern, and
      if the timing of retinal gene loss is associated with the entrance of mammalian
      lineages into subterranean environments. Sequence data were obtained from the
      publically available genomes of the Cape golden mole (Chrysochloris asiatica),
      naked mole-rat (Heterocephalus glaber) and star-nosed mole (Condylura cristata)
      for 65 genes associated with phototransduction, the visual cycle, and other
      retinal functions. Gene sequences were inspected for inactivating mutations and,
      when present, pseudogene sequences were compared to sequences from subaerial
      outgroup species. To test whether retinal degeneration is correlated with
      historical entrances into subterranean environments, estimated dates of retinal
      gene inactivation were compared to the fossil record and phylogenetic inferences
      of ancestral fossoriality. Our results show that (1) lower levels of light
      available to the retina correspond with an increase in the number of retinal
      pseudogenes, (2) retinal protein networks generally degrade in a predictable
      manner, although the extensive loss of cone phototransduction genes in
      Heterocephalus raises further questions regarding SWS1-cone monochromacy versus
      functional rod monochromacy in this species, and (3) inactivation dates of
      retinal genes usually post-date inferred entrances into subterranean habitats. 

PMID- 24859680
TI  - Public health workers and vaccination coverage in Eastern China: a health
      economic analysis.
AB  - BACKGROUND: Vaccine-preventable diseases cause more than one million deaths among
      children under 5 years of age every year. Public Health Workers (PHWs) are needed
      to provide immunization services, but the role of human resources for public
      health as a determinant of vaccination coverage at the population level has not
      been assessed in China. The objective of this study was to test whether PHW
      density was positively associated with childhood vaccination coverage in Zhejiang
      Province, East China. METHODS: The vaccination coverage rates of Measles
      Containing Vaccine (MCV), Diphtheria, Tetanus and Pertussis combined vaccine
      (DTP), and Poliomyelitis Vaccine (PV) were chosen as the dependent variables.
      Vaccination coverage data of children aged 13-24 months for each county in
      Zhejiang Province were taken from the Zhejiang Immunization Information System
      (ZJIIS). Aggregate PHW density was an independent variable in one set of
      regressions, and Vaccine Personnel (VP) and other PHW densities were used
      separately in another set. Data on densities of PHW and VP were taken from a
      national investigation on EPI launched by Ministry of Health of China in 2013. We
      controlled other determinants that may influence the vaccination coverage like
      Gross Domestic Product (GDP) per person, proportion of migrant children aged <7
      years, and land area. These data were taken from Zhejiang Provincial Bureau of
      Statistics and ZJIIS. RESULTS: PHW density was significantly influence the
      coverage rates of MCV [Adjusted Odds Ratio(AOR) = 4.29], DTP3(AOR = 2.16), and
      PV3 (AOR = 3.30). However, when the effects of VPs and other PHWs were assessed
      separately, we found that VP density was significantly associated with coverage
      of all three vaccinations (MCV AOR = 7.05; DTP3 AOR = 1.82; PV3 AOR = 4.83),
      while other PHW density was not. Proportion of migrant children < 7 years and
      Land area were found as negative and significant determinants for vaccination
      coverage, while GDP per person had no effect on vaccination coverage.
      CONCLUSIONS: A higher density of PHWs (VP) would improve the availability of
      immunization services over time and space, which may increase the possibility of
      achieving a higher childhood vaccination coverage rate. It was indicated that the
      level of GDP per person had no association with the improved vaccination coverage
      after controlling for other potential factors. Our findings implicated that PHW
      density was a major constraint on immunization coverage in Zhejiang Province.

PMID- 24859682
TI  - Homoplastic evolution and host association of Eriophyoidea (Acari, Prostigmata)
      conflict with the morphological-based taxonomic system.
AB  - The superfamily Eriophyoidea is exceptionally diverse and its members are highly
      host-specific. Currently, the taxonomy of this group is based on morphology only.
      However, phylogenetic relationships in this group could be incorrect if the
      diagnostic morphological characters are homoplastic. Therefore, the phylogeny of
      112 representative taxa of Eriophyoidea from China was determined using 18S, 28S
      D2-5 and D9-10 rRNA. Phylogenetic relationships were inferred through Bayesian,
      maximum likelihood and maximum parsimony methods, and then a number of clades or
      major clades were defined according to robust phylogenetic topologies combined
      with morphological comparison. Tests of monophyly showed that two of three
      families of Eriophyoidea as well as one subfamily and four tribes were not
      monophyletic. Ancestral character state reconstruction (ACSR) showed that five
      diagnostic morphological characters evolved several times, confounding the
      current taxonomy. Additionally, reconstruction of the history of host plant
      colonization suggested host switching occurred in a limited range of host plants.
      The host association data made it possible to determine taxonomic relationships
      more accurately. These results show that by integrating morphological and
      molecular information and host plant choice, it is possible to obtain a more
      accurate taxonomy and a deeper phylogenetic understanding of Eriophyoidea. 

PMID- 24859683
TI  - Evolutionary history of two divergent Dmrt1 genes reveals two rounds of
      polyploidy origins in gibel carp.
AB  - Polyploidy lineages, despite very rare in vertebrates, have been proposed to play
      significant role in speciation and evolutionary success, but the occurrence
      history and consequences are still largely unknown. In this study, we used the
      conserved Dmrt1 to analyze polyploidy occurrence and evolutionary process in
      polyploid gibel carp. We identified two divergent Dmrt1 genes and respectively
      localized the two genes on three homologous chromosomes. Subsequently, the
      corresponding full-length cDNAs and genomic sequences of Dmrt1 genes were also
      characterized from the closely related species including Carassius auratus
      auratus and Cyprinus carpio, and their two Dmrt1 genes were respectively
      localized on two homologous chromosomes. Significantly, the evolutionary
      relationship analyses among cDNA and genomic DNA sequences of these Dmrt1 genes
      revealed two rounds of polyploidy origins in the gibel carp: an early polyploidy
      might result in an common tetraploid ancestor of Carassius auratus gibelio,
      Carassius auratus auratus and Cyprinus carpio before 18.49 million years ago
      (Mya), and an late polyploidy might occur from evolutionary branch of Carassius
      auratus at around 0.51 Mya, which lead to the occurrence of the hexaploid gibel
      carp. Therefore, this study provides clear genetic evidence for understanding
      occurrence time and historical process of polyploidy in polyploid vertebrates. 

PMID- 24859684
TI  - Phylogenetic relationships of the ciliate class Heterotrichea (Protista,
      Ciliophora, Postciliodesmatophora) inferred from multiple molecular markers and
      multifaceted analysis strategy.
AB  - The ciliate class Heterotrichea is defined by somatic dikinetids bearing
      postciliodesmata, by an oral apparatus consisting of a paroral membrane and an
      adoral zone of membranelles, as well as by features of nuclear division involving
      extramacronuclear microtubules. Although phylogenetic interrelationships among
      heterotrichs have been analyzed several times, deeper nodes of the heterotrichean
      tree of life remain poorly resolved. To cast more light on the evolutionary
      history of heterotricheans, we performed phylogenetic analyses of multiple loci
      (18S rRNA gene, ITS1-5.8S rRNA-ITS2 region, and 28S rRNA gene) using traditional
      tree-building phylogenetic methods and statistical tree topology tests as well as
      phylogenetic networks, split spectrum analysis and quartet likelihood mapping.
      This multifaceted approach has shown that (1) Peritromus is very likely an
      adelphotaxon of all other heterotrichs; (2) Spirostomum and Anigsteinia are
      sister taxa and their common monophyletic origin is strongly supported by a
      uniquely posteriorly-thickened paroral membrane; (3) the monotypic family
      Chattonidiidae should be suppressed because its type genus clusters within the
      family Condylostomatidae; and (4) new families are needed for Gruberia and Fabrea
      because their affiliation with Spirostomidae and Climacostomidae, respectively,
      is not supported by molecular phylogenies nor the fine structure of the paroral
      membrane. 

PMID- 24859686
TI  - Effect of the Wnt1/beta-catenin signalling pathway on human embryonic pulmonary
      fibroblasts.
AB  - Idiopathic pulmonary fibrosis (IPF) is a fibrotic lung disease associated with a
      high rate of mortality, characterised by an accumulation of
      fibroblasts/myofibroblasts in the fibroblastic foci (FF) and by an excessive
      deposition of extracellular matrix (ECM) in the lung parenchyma. The pathogenesis
      of this fatal disorder remains unclear. Previous evidence suggests that
      myofibroblasts are key effectors of the deposition of ECM. In the present study,
      human embryonic pulmonary fibroblast (HEPF) cells were incubated with different
      concentrations of Wnt1. The present study revealed that cell proliferation
      improved following stimulation using different concentrations of Wnt1 in a
      concentration-dependent manner. When the concentration exceeded 20 ug/l, cell
      proliferation was significant (P<0.05) and the cell expression of alpha-SMA,
      vimentin and collagen I mRNA, as well as protein expression, significantly
      increased (P<0.05). Bronchoalveolar lavage fluid (BALF) was then obtained from
      bleomycin (BLM)-induced models of pulmonary fibrosis. HEPF cells were cultured
      with Dulbecco's modified Eagle's medium plus BALF. The mRNA and protein
      expression of alpha-SMA, vimentin and collagen I significantly increased and
      these increases were associated with beta-catenin. Furthermore, following being
      infected with the lentivirus expressing beta-catenin shRNA, HEPF cells were
      cultured with BALF. However, the mRNA and protein expression of alpha-SMA,
      vimentin and collagen I did not increase significantly. The present study
      suggested that the Wnt1/beta-catenin signalling pathway can promote HEPF cell
      proliferation and induced HEPF cells can change into myofibroblasts and promote
      ECM deposition. These findings may provide a theoretical basis for the treatment
      of IPF. 

PMID- 24859688
TI  - Structural insights into functional lipid-protein interactions in secondary
      transporters.
AB  - BACKGROUND: Structural evidences with functional corroborations have revealed
      distinct features of lipid-protein interactions especially in channels and
      receptors. Many membrane embedded transporters are also known to require specific
      lipids for their functions and for some of them cellular and biochemical data
      suggest tight regulation by the lipid bilayer. However, molecular details on
      lipid-protein interactions in transporters are sparse since lipids are either
      depleted from the detergent solubilized transporters in three-dimensional
      crystals or not readily resolved in crystal structures. Nevertheless the steady
      increase in the progress of transporter structure determination contributed more
      examples of structures with resolved lipids. SCOPE OF REVIEW: This review gives
      an overview on transporter structures in complex with lipids reported to date and
      discusses commonly encountered difficulties in the identification of functionally
      significant lipid-protein interactions based on those structures and functional
      in vitro data. Recent structures provided molecular details into regulation
      mechanism of transporters by specific lipids. The review highlights common
      findings and conserved patterns for distantly related transporter families to
      draw a more general picture on the regulatory role of lipid-protein interactions.
      MAJOR CONCLUSIONS: Several common themes of the manner in which lipids directly
      influence membrane-mediated folding, oligomerization and structure stability can
      be found. Especially for LeuT-like fold transporters similarities in structurally
      resolved lipid-protein interactions suggest a common way in which transporter
      conformations are affected by lipids even in evolutionarily distinct
      transporters. Lipids appear to play an additional role as joints mechanically
      reinforcing the inverted repeat topology, which is a major determinant in the
      alternating access mechanism of secondary transporters. GENERAL SIGNIFICANCE:
      This review brings together and adds to the repertoire of knowledge on lipid
      protein interactions of functional significance presented in structures of
      membrane transporters. Knowledge of specific lipid-binding sites and modes of
      lipid influence on these proteins not only accomplishes the molecular description
      of transport cycle further, but also sheds light into localization dependent
      differences of transporter function. This article is part of a Special Issue
      entitled Structural biochemistry and biophysics of membrane proteins.

PMID- 24859687
TI  - Molecular insights into proton coupled peptide transport in the PTR family of
      oligopeptide transporters.
AB  - BACKGROUND: Cellular uptake of small peptides is an important physiological
      process mediated by the PTR family of proton-coupled peptide transporters. In
      bacteria peptides can be used as a source of amino acids and nitrogen. Similarly
      in humans peptide transport is the principle route for the uptake and retention
      of dietary protein in the form of short di- and tri-peptides for cellular
      metabolism. SCOPE OF THE REVIEW: Recent crystal structures of bacterial PTR
      family transporters, combined with biochemical studies of transport have revealed
      key molecular details underpinning ligand promiscuity and the mechanism of proton
      coupled transport within the family. MAJOR CONCLUSIONS: Pairs of salt bridge
      interactions between transmembrane helices work in tandem to orchestrate
      alternating access transport within the PTR family. Key roles for residues
      conserved between bacterial and eukaryotic homologues suggest a conserved
      mechanism of peptide recognition and transport that in some cases has been subtly
      modified in individual species. GENERAL SIGNIFICANCE: Physiological studies on
      PepT1 and PepT2, the mammalian members of this family, have identified these
      transporters as being responsible for the uptake of many pharmaceutically
      important drug molecules, including antibiotics and antiviral medications and
      demonstrated their promiscuity can be used for improving the oral bioavailability
      of poorly absorbed compounds. The insights gained from recent structural studies
      combined with previous physiological and biochemical analyses are rapidly
      advancing our understanding of this medically important transporter superfamily.
      This article is part of a Special Issue entitled Structural biochemistry and
      biophysics of membrane proteins.

PMID- 24859689
TI  - Diagnostic and therapeutic issues for patients with advanced non-small cell lung
      cancer harboring anaplastic lymphoma kinase rearrangement: European vs. US
      perspective (review).
AB  - The recent availability of crizotinib in clinical practice, for the treatment of
      patients with advanced non-small cell lung cancer (NSCLC) selected by the
      presence of anaplastic lymphoma kinase (ALK) rearrangement, has relevant
      implications for both the diagnostic phase and the treatment choices. In the
      United States, crizotinib was approved by the Food and Drug Administration (FDA)
      in 2011 for patients with ALK positivity detected by FDA-approved companion
      diagnostic test. As of January, 2014, the only FDA-approved diagnostic test is
      Vysis ALK Break-Apart FISH Probe Kit. In Europe, European Medicines Agency (EMA)
      approved crizotinib for ALK-positive patients in 2012, without specifying the
      type of test used for determining the positivity. FISH remains the reference
      technique for ALK determination, but, if fully validated, immunohistochemistry
      could challenge the current ALK screening practice. Given the robust evidence of
      activity of crizotinib in ALK-positive patients both pretreated and chemotherapy
      naive, and the favourable tolerability profile of the drug, many oncologists
      would prefer to administer the drug as early as possible. This is technically
      feasible in the United States, where crizotinib was approved well before the
      availability of the results of the randomized phase III trial comparing the drug
      with standard second-line chemotherapy, and the use of crizotinib in ALK-positive
      patients is not restricted to a specific line of treatment. On the contrary, in
      Europe, differently from the FDA decision, crizotinib cannot be used in
      chemotherapy-naive patients. In both realities, a deeper knowledge of mechanisms
      of resistance, the role of repeated biopsies, the treatment strategy for patients
      experiencing disease progression with crizotinib, the choice of the best
      chemotherapy regimen are challenging topics for the management of ALK-positive
      patients in clinical practice.

PMID- 24859690
TI  - Autosomal recessive bestrophinopathy associated with angle-closure glaucoma.
AB  - PURPOSE: Abnormalities in the BEST1 gene have recently been recognised as causing
      autosomal recessive bestrophinopathy (ARB). ARB has been noted to have a variable
      phenotypic presentation, distinct from that of autosomal dominant Best
      vitelliform macular dystrophy (BVMD). Both conditions are associated with
      deposits in the retina, a reduced or absent electro-oculography (EOG) light rise,
      and the risk of developing angle-closure glaucoma. Herein, we describe the
      clinical and genetic characteristics of a young male diagnosed with ARB
      associated with angle-closure glaucoma resulting from a novel homozygous mutation
      in BEST1. METHODS: All research involved in this case adhered to the tenets of
      the Declaration of Helsinki. The proband underwent slitlamp examination, retinal
      autofluorescence imaging and optical coherence tomography after presenting with
      deteriorating vision. The findings prompted genetic testing with bi-directional
      DNA sequencing of coding and flanking intronic regions of BEST1. The proband's
      family members were subsequently screened. RESULTS: A provisional diagnosis of
      ARB was made based on the findings of subretinal and schitic lesions on
      fundoscopy and retinal imaging, together with abnormal EOG and
      electroretinography. Genetic testing identified a novel homozygous mutation in
      BEST1, c.636+1 G>A. Family members were found to carry one copy of the mutation
      and had no clinical or electrophysiological evidence of disease. The proband was
      additionally diagnosed with angle-closure glaucoma requiring topical therapy,
      peripheral iridotomies and phacoemulsification. CONCLUSIONS: Phenotypic overlap,
      reduced penetrance, variable expressivity and the ongoing discovery of new forms
      of bestrophinopathies add to the difficulty in distinguishing these retinal
      diseases. All patients diagnosed with ARB or BVMD should be examined for narrow
      angles and glaucoma, given their frequent association with these conditions.

PMID- 24859691
TI  - Spontaneous perceptual facial distortions correlate with ventral occipitotemporal
      activity.
AB  - Prosopometamorphopsia is a disorder of face perception in which faces appear
      distorted to the perceiver. The neural basis of prosopometamorphopsia is unclear,
      but may involve abnormal activity in face-selective areas in the ventral occipito
      temporal pathway. Here we present the case of AS, a 44-year-old woman who reports
      persistent perceptual distortions of faces with no known cause. AS was presented
      with facial images and rated the magnitude of her distortions while activity in
      her core face areas and other areas in the ventral visual pathway was measured
      using functional magnetic resonance imaging. The magnitude of her distortions was
      positively correlated with signal changes in the right occipital face area (OFA)
      and right fusiform face area (FFA), as well as right V1-V3, and right lateral
      occipital cortex (LOC). There was also a trend for a significant correlation with
      signal in the left OFA and right inferior frontal gyrus (IFG), but not in the
      right or left superior temporal sulcus (STS). These results suggest that AS'
      prosopometamorphopsia reflects anomalous activity in face-processing network,
      particularly in the ventral occipitotemporal cortex. 

PMID- 24859692
TI  - Galectin fingerprinting in naso-sinusal diseases.
AB  - Galectins, a family of endogenous lectins, are multifunctional effectors that act
      at various sites and can be used in immunohistochemical localization studies of
      diseased states. Since they form a potentially cooperative and antagonistic
      network, we tested the hypothesis that histopathological fingerprinting of
      galectins could refine the molecular understanding of naso-sinusal pathologies.
      Using non-cross-reactive antibodies against galectin-1, -3, -4, -7, -8 and -9, we
      characterized the galectin profiles in chronic rhinosinusitis, nasal polyposis,
      inverted papillomas and squamous cell carcinomas. The expression, signal location
      and quantitative parameters describing the percentage of positive cells and
      labeling intensity were assessed for various cases. We discovered that inverted
      papillomas showed a distinct galectin immunohistochemical profile. Indeed,
      epithelial overexpression of galectin-3 (p=0.0002), galectin-4 (p<10-6), galectin
      7 (p<10-6) and galectin-9 (p<10-6) was observed in inverted papillomas compared
      to non-malignant diseases. Regarding carcinomas, we observed increased expression
      of galectin-9 (p<10-6) in epithelial cells compared to non-tumor pathologies. Our
      results suggest that galectin-3, -4, -7 and -9 could be involved in the biology
      of inverted papillomas. In addition, we observed that the expression of galectin
      in naso-sinusal diseases seems to be affected by tumor progression and not
      inflammatory or allergic phenomena. 

PMID- 24859693
TI  - Hydrophilic interaction liquid chromatography coupled with tandem mass
      spectrometry for acidic herbicides and metabolites analysis in fresh water.
AB  - Theoretical papers and environmental applications of hydrophilic interaction
      liquid chromatography (HILIC) have been published for a wide range of analytes,
      but to our knowledge, no study focused on acidic herbicides (e.g., triketones,
      phenoxy acids, sulfonylurea, and acidic metabolites of chloroacetanilides).
      Matrix effects are the main obstacle to natural sample analysis by liquid
      chromatography coupled with tandem mass spectrometry (MS) via an electrospray
      ionization (ESI) interface. Therefore, we paid particular attention on limiting
      interference by (i) adapting the emerging HILIC technique, which is generally
      considered more sensitive than conventional reversed phase liquid chromatography
      and (ii) optimizing the solid phase extraction (SPE) step using a design of
      experiment. A rapid and reliable off line SPE-HILIC-ESI-MS/MS method was thus
      developed for the quantification of acidic herbicides in fresh water, with limits
      of quantifications (LOQs) ranging from 5 to 22 ng L(-1). Then, the analysis of
      freshwater samples highlighted the robustness of the method, and the importance
      of the chloroacetanilides metabolites among the studied analytes. 

PMID- 24859694
TI  - The effects of henna (hair dye) on the embryonic development of zebrafish (Danio
      rerio).
AB  - The powder of henna is extensively used as decorative skin paint for nail
      coloring and as a popular hair dye in Asian countries. Its human health risk is
      extensive, and it is frequently released as waste into the aquatic environment
      raising the concerns. Zebrafish (Danio rerio) embryos were employed to study the
      developmental effects of henna. Normal fertilized zebrafish embryos under
      standard water were selected for the control and test chambers. Three
      predetermined sublethal concentrations (100, 200, and 275 MUM) of henna in 24
      well cell culture plates were tested on 1-h postfertilized embryo (pfe) for 96 h.
      Observation for rates of survival and mortality was recorded; digital camera was
      used to image morphological anomalies of embryos with a stereomicroscope; and
      functional abnormalities at 24, 48, 72, and 96 h were performed. The hatching
      rates of embryos were reduced significantly when treated with 200 and 275 MUM or
      higher concentrations of henna. Slow blood circulation in the whole body was
      observed with a median effect on hatching exposed to 200 and 275 MUM of henna at
      48-h pfe. At 72- and 96-h pfe, blood circulation was ceased in the whole body but
      still had a heartbeat. At 96-h pfe, pericardial sac edema, yolk sac edema, head
      deformation, spine crooked malformation, and tail malformation (bent tails or
      hook-like tails) were observed in the surviving larvae at 100 MUM. In summary,
      exposure to henna at 100, 200, and 275 MUM causes some altered morphological and
      physiological abnormalities including increased mortality, hatching delay, slow
      blood circulation, pericardial sac edema, yolk sac edema, abnormal body axes,
      twisted notochord, tail deformation, weak heartbeat, and growth retardation and
      was also detected in some treated embryos and groups having adverse effects on
      embryonic development of zebrafish provoking potential human developmental risk
      studies.

PMID- 24859696
TI  - Trace elements in size-segregated urban aerosol in relation to the anthropogenic
      emission sources and the resuspension.
AB  - Size segregated particulate samples of atmospheric aerosols in urban site of
      continental part of Balkans were collected during 6 months in 2008. Six stages
      impactor in the size ranges: Dp <= 0.49 MUm, 0.49 < Dp <= 0.95 MUm, 0.95 < Dp <=
      1.5 MUm, 1.5 < Dp <= 3.0 MUm, 3.0 < Dp <= 7.2 MUm, and 7.2 < Dp <= 10.0 MUm was
      applied for sampling. ICP-MS was used to quantify elements: Al, As, Bi, Ca, Cd,
      Co, Cr, Cu, Fe, Ga, K, Li, Na, Ni, Mg, Mn, Pb, Sb, V, and Zn. Two main groups of
      elements were investigated: (1) K, V, Ni, Zn, Pb, As, and Cd with high domination
      in nuclei mode indicating the combustion processes as a dominant sources and (2)
      Al, Fe, Ca, Mg, Na, Cr, Ga, Co, and Li in coarse mode indicating mechanical
      processes as their main origin. The strictly crustal origin is for Mg, Fe, Ca,
      and Co while for As, Cd, K, V, Ni, Cu, Pb, and Zn dominates the anthropogenic
      influence. The PCA analysis has shown that main contribution is of resuspension
      (PC1, sigma(2) ~ 30 %) followed by traffic (PC2, sigma(2) ~ 20 %) that are
      together contributing around 50 % of elements in the investigated urban aerosol.
      The EF model shows that major origin of Cd, K, V, Ni, Cu, Pb, Zn, and As in the
      fine mode is from the anthropogenic sources while increase of their contents in
      the coarse particles indicates their deposition from the atmosphere and soil
      contamination. This approach is useful for the assessment of the local
      resuspension influence on element's contents in the aerosol and also for the
      evaluation of the historical pollution of soil caused by deposition of metals
      from the atmosphere.

PMID- 24859695
TI  - Application of the triolein-embedded cellulose acetate membrane passive sampler
      for monitoring of polycyclic aromatic hydrocarbons in water.
AB  - Triolein-embedded cellulose acetate membrane (TECAM) can be used as a passive
      sampler to measure hydrophobic organic contaminants in water. Uptake constant
      rates (k u ) for polycyclic aromatic hydrocarbons (PAHs) by TECAM sampling were
      measured under different hydrodynamic conditions. The measured k u values were
      modeled to enable the quantification of time weighed average (TWA) concentrations
      of PAHs in the field. An empirical relationship that enables the calculation of
      in situ k u values of chemicals using performance reference compounds (PRCs) was
      derived and its application was demonstrated in a field study. The results showed
      that freely dissolved concentrations of hydrophobic organic compounds (HOCs) can
      be accurately measured in the field using TECAM method based on empirical uptake
      models calibrated with PRCs. 

PMID- 24859697
TI  - Cadmium and copper toxicity in three marine macroalgae: evaluation of the
      biochemical responses and DNA damage.
AB  - Marine macroalgae have evolved a different mechanism to maintain physiological
      concentrations of essential metal ions and non-essential metals. The objective of
      the present work was to evaluate the antioxidant response and DNA damage of
      copper and cadmium ions in three halophytes, namely, Acanthophora spicifera,
      Chaetomorpha antennina, and Ulva reticulata. Accumulation of copper was
      significantly higher (P < 0.05) than that of cadmium. Biochemical responses
      showed that copper was considerably more toxic than cadmium (P < 0.05). Decreases
      in glutathione content and fluctuations of super oxide dismutase, catalase, and
      glutathione peroxidase activities were observed corresponding to time and
      concentration of exposure. Interestingly, it was also observed that antioxidant
      levels decreased as a result of metal accumulation, which may be due to free
      radicals generated by copper and cadmium in seaweeds. The present study also
      showed that copper and cadmium increased oxidative stress and induced antioxidant
      defense systems against reactive oxygen species. The order of toxicity for metals
      in the studied seaweeds was U. reticulata > A. spicifera > C. antennina. DNA
      damage index analysis supported that copper was significantly (P < 0.05) more
      toxic than cadmium. Bioaccumulation, biochemical responses, and DNA damage
      observed in the here analyzed marine macroalgae after exposure to selected metals
      indicate that these marine organisms represent useful bioindicators of marine
      pollution.

PMID- 24859699
TI  - Removal of As(III) and As(V) using iron-rich sludge produced from coal mine
      drainage treatment plant.
AB  - To test the feasibility of the reuse of iron-rich sludge (IRS) produced from a
      coal mine drainage treatment plant for removing As(III) and As(V) from aqueous
      solutions, we investigated various parameters, such as contact time, pH, initial
      As concentration, and competing ions, based on the IRS characterization. The IRS
      consisted of goethite and calcite, and had large surface area and small
      particles. According to energy dispersive X-ray spectroscopy mapping results, As
      was mainly removed by adsorption onto iron oxides. The adsorption kinetic studies
      showed that nearly 70 % adsorption of As was achieved within 1 h, and the pseudo
      second-order model well explained As sorption on the IRS. The adsorption isotherm
      results agreed with the Freundlich isotherm model, and the maximum adsorption
      capacities for As(III) and As(V) were 66.9 and 21.5 mg/g, respectively, at 293 K.
      In addition, the adsorption showed the endothermic character. At high pH or in
      the presence of phosphate, the adsorption of As was decreased. When the
      desorption experiment was conducted to reuse the IRS, 85 % As was desorbed with
      1.0 N NaOH. In the column experiment, adsorbed As in real acid mine drainage was
      43 % of the maximum adsorbed amount of As in the batch test. These results
      suggested that the IRS is an effective adsorbent for As and can be effectively
      applied for the removal of As in water and wastewater.

PMID- 24859698
TI  - Metal partitioning in plant-substrate-water compartments under EDDS-assisted
      phytoextraction of pyrite waste with Brassica carinata A. Braun.
AB  - Soil amendment with chelating agents can increase metal uptake and translocation
      in biomass species through increased metal bioavailability together with possible
      increases in metal leaching. In this study, we assessed the efficiency and
      environmental risk of the fast-degradable [S,S]-EDDS. Cu, Pb and Zn uptake in pot
      cultivated Brassica carinata A. Braun, residual substrate metal bioavailability
      and leaching were investigated after one cycle of EDDS-assisted phytoextraction
      in mixed metal-contaminated pyrite waste, which is characterised by high Fe
      content. The chelator was supplied at doses of 2.5 and 5 mmol EDDS kg(-1) waste 1
      week before harvest and 1 mmol EDDS kg(-1) waste repeated five times at 5- and 10
      day intervals during the growing cycle. Here we demonstrate that EDDS generally
      increases shoot metal concentrations-especially of Cu-but only seldom improves
      removals because of markedly impaired growth. Considerable phytotoxicity and Cu
      leaching occurred under repeated EDDS treatments, although environmental risks
      may also arise from the single, close-to-harvest applications as Cu
      bioavailability in waste at plant harvest still remained very high (up to +67 %
      at 5 mmol EDDS kg(-1) vs. untreated controls). The residual bioavailability of Zn
      and Pb was instead generally reduced, perhaps due to shifts in cation exchange,
      whereas Fe mobility was not apparently affected. The amount of metals removed by
      plants represented a small fraction of the bioavailable pool (<1 %), and
      mobilised metals quickly reached deep layers in the substrate. We conclude that
      EDDS assistance can provide only some limited opportunities for improving
      phytoremediation of pyrite waste, major benefits being achieved by low doses to
      be traditionally applied shortly before harvest, with due attention to limiting
      groundwater pollution.

PMID- 24859701
TI  - Arsenic and copper stabilisation in a contaminated soil by coal fly ash and green
      waste compost.
AB  - In situ metal stabilisation by amendments has been demonstrated as an appealing
      low-cost remediation strategy for contaminated soil. This study investigated the
      short-term leaching behaviour and long-term stability of As and Cu in soil
      amended with coal fly ash and/or green waste compost. Locally abundant inorganic
      (limestone and bentonite) and carbonaceous (lignite) resources were also studied
      for comparison. Column leaching experiments revealed that coal fly ash
      outperformed limestone and bentonite amendments for As stabilisation. It also
      maintained the As stability under continuous leaching of acidic solution, which
      was potentially attributed to high-affinity adsorption, co-precipitation, and
      pozzolanic reaction of coal fly ash. However, Cu leaching in the column
      experiments could not be mitigated by any of these inorganic amendments,
      suggesting the need for co-addition of carbonaceous materials that provides
      strong chelation with oxygen-containing functional groups for Cu stabilisation.
      Green waste compost suppressed the Cu leaching more effectively than lignite due
      to the difference in chemical composition and dissolved organic matter. After 9
      month soil incubation, coal fly ash was able to minimise the concentrations of As
      and Cu in the soil solution without the addition of carbonaceous materials.
      Nevertheless, leachability tests suggested that the provision of green waste
      compost and lignite augmented the simultaneous reduction of As and Cu
      leachability in a fairly aggressive leaching environment. These results highlight
      the importance of assessing stability and remobilisation of sequestered metals
      under varying environmental conditions for ensuring a plausible and enduring soil
      stabilisation. 

PMID- 24859700
TI  - Degradation of recalcitrant aliphatic and aromatic hydrocarbons by a dioxin
      degrader Rhodococcus sp. strain p52.
AB  - This study investigates the ability of Rhodococcus sp. strain p52, a dioxin
      degrader, to biodegrade petroleum hydrocarbons. Strain p52 can use linear alkanes
      (tetradecane, tetracosane, and dotriacontane), branched alkane (pristane), and
      aromatic hydrocarbons (naphthalene and phenanthrene) as sole carbon and energy
      sources. Specifically, the strain removes 85.7 % of tetradecane within 48 h at a
      degradation rate of 3.8 mg h(-1) g(-1) dry cells, and 79.4 % of tetracosane, 66.4
      % of dotriacontane, and 63.9 % of pristane within 9-11 days at degradation rates
      of 20.5, 14.7, and 20.3 mg day(-1) g(-1) dry cells, respectively. Moreover,
      strain p52 consumes 100 % naphthalene and 55.3 % phenanthrene within 9-11 days at
      respective degradation rates of 16 and 12.9 mg day(-1) g(-1) dry cells.
      Metabolites of the petroleum hydrocarbons by strain p52 were analyzed. Genes
      encoding alkane-hydroxylating enzymes, including cytochrome P450 (CYP450) enzyme
      (CYP185) and two alkane-1-monooxygenases, were amplified by polymerase chain
      reaction. The transcriptional activities of these genes in the presence of
      petroleum hydrocarbons were detected by reverse transcription-polymerase chain
      reaction. The results revealed potential of strain p52 to degrade petroleum
      hydrocarbons.

PMID- 24859702
TI  - Biodegradation of organic pollutants in saline wastewater by halophilic
      microorganisms: a review.
AB  - Agro-food, petroleum, textile, and leather industries generate saline wastewater
      with a high content of organic pollutants such as aromatic hydrocarbons, phenols,
      nitroaromatics, and azo dyes. Halophilic microorganisms are of increasing
      interest in industrial waste treatment, due to their ability to degrade hazardous
      substances efficiently under high salt conditions. However, their full potential
      remains unexplored. The isolation and identification of halophilic and
      halotolerant microorganisms from geographically unrelated and geologically
      diverse hypersaline sites supports their application in bioremediation processes.
      Past investigations in this field have mainly focused on the elimination of
      polycyclic aromatic hydrocarbons and phenols, whereas few studies have
      investigated N-aromatic compounds, such as nitro-substituted compounds, amines,
      and azo dyes, in saline wastewater. Information regarding the growth conditions
      and degradation mechanisms of halophilic microorganisms is also limited. In this
      review, we discuss recent research on the removal of organic pollutants such as
      organic matter, in terms of chemical oxygen demand (COD), dyes, hydrocarbons, N
      aliphatic and N-aromatic compounds, and phenols, in conditions of high salinity.
      In addition, some proposal pathways for the degradation of aromatic compounds are
      presented. 

PMID- 24859703
TI  - Behaviour of oxyfluorfen in soils amended with edaphic
      biostimulants/biofertilizers obtained from sewage sludge and chicken feathers.
      Effects on soil biological properties.
AB  - We studied the behaviour of oxyfluorfen herbicide at a rate of 4 l ha(-1) on
      biological properties of a Calcaric Regosol amended with two edaphic
      biostimulants/biofertilizers (SS, derived from sewage sludge; and CF, derived
      from chicken feathers). Oxyfluorfen was surface broadcast on 11 March 2013. Two
      days after application of oxyfluorfen to soil, both biostimulants/biofertilizers
      (BS) were also applied to the soil. An unamended soil without oxyfluorfen was
      used as control. For 2, 4, 7, 9, 20, 30, 60, 90 and 120 days of the application
      of herbicide to the soil and for each treatment, the soil dehydrogenase, urease,
      beta-glucosidase and phosphatase activities were measured. For 2, 7, 30 and 120
      days of the application of herbicide to the soil and for each treatment, soil
      microbial community was determined. The application of both BS to soil without
      the herbicide increased the enzymatic activities and soil biodiversity, mainly at
      7 days of beginning the experiment. However, this stimulation was higher in the
      soil amended with SS than for CF. The application of herbicide in organic-amended
      soils decreased the inhibition of soil enzymatic activities and soil
      biodiversity. Possibly, the low-molecular-weight protein content easily
      assimilated by soil microorganisms is responsible for less inhibition of these
      soil biological properties.

PMID- 24859704
TI  - Investigations on mobility of carbon colloid supported nanoscale zero-valent iron
      (nZVI) in a column experiment and a laboratory 2D-aquifer test system.
AB  - Nanoscale zero-valent iron (nZVI) has recently gained great interest in the
      scientific community as in situ reagent for installation of permeable reactive
      barriers in aquifer systems, since nZVI is highly reactive with chlorinated
      compounds and may render them to harmless substances. However, nZVI has a high
      tendency to agglomerate and sediment; therefore it shows very limited transport
      ranges. One new approach to overcome the limited transport of nZVI in porous
      media is using a suited carrier colloid. In this study we tested mobility of a
      carbon colloid supported nZVI particle "Carbo-Iron Colloids" (CIC) with a mean
      size of 0.63 MUm in a column experiment of 40 cm length and an experiment in a
      two-dimensional (2D) aquifer test system with dimensions of 110 * 40 * 5 cm.
      Results show a breakthrough maximum of 82 % of the input concentration in the
      column experiment and 58 % in the 2D-aquifer test system. Detected residuals in
      porous media suggest a strong particle deposition in the first centimeters and
      few depositions in the porous media in the further travel path. Overall, this
      suggests a high mobility in porous media which might be a significant enhancement
      compared to bare or polyanionic stabilized nZVI.

PMID- 24859705
TI  - Organic matter and pollutants monitoring in reed bed systems for sludge
      stabilization: a case study.
AB  - In this study, results about sludge stabilization and pollutant monitoring in a
      reed bed system (RBSs) situated in Central Italy (Colle di Compito, 4,000 p.e.)
      were presented. In order to evaluate the process of sludge stabilization,
      parameters that highlighted the biochemical, chemical and chemico-structural
      properties of organic sludge matter have been followed during the entire period
      of operation (7 years). Moreover, the trend of heavy metals (bioavailable
      fractions and total content) and toxic organic compounds (LAS, NPE and DEHP) was
      monitored during all the period. The trend of all parameters related clearly
      demonstrated that sludge stabilization successfully proceeded in RBS. Moreover,
      through statistical analysis modelling, it is possible to determine how the
      stabilization process proceeded in terms of organic matter mineralization and
      humification, and how these processes influenced the content of pollutant
      compounds present in the stabilized sludges.

PMID- 24859706
TI  - Probabilistic risk assessment of diuron and prometryn in the Gwydir River
      catchment, Australia, with the input of a novel bioassay based on algal growth.
AB  - A probabilistic risk assessment of the selected herbicides (diuron and prometryn)
      in the Gwydir River catchment was conducted, with the input of the EC50 values
      derived from both literature and a novel bioassay. Laboratory test based on
      growth of algae exposed to herbicides assayed with a microplate reader was used
      to examine the toxicity of diuron and prometryn on the growth of Chlorella
      vulgaris. Both herbicides showed concentration dependent toxicity in inhibiting
      the growth of Chlorella during the exposure period of 18-72 h. Diuron caused more
      toxicity as judged by growth rates than prometryn. Thalaba Creek at Merrywinebone
      was identified as the 'hotspot' for diuron and prometryn risk in the Gwydir
      catchment. The use of microplate assays coupled with probabilistic risk
      assessment is recommended for rapid assessment of ecotoxicity of indigenous
      species, allowing identification of locations in river catchments requiring
      environmental management.

PMID- 24859707
TI  - Dioxin-related compounds in breast milk of women from Vietnamese e-waste
      recycling sites: levels, toxic equivalents and relevance of non-dietary exposure.
AB  - Although informal e-waste recycling sites (EWRSs) are hotspots of both
      polychlorinated and polybrominated dibenzo-p-dioxins/dibenzofurans (PCDD/Fs and
      PBDD/Fs), human exposure to the latter has not been studied in details. This
      study investigated the accumulation levels and profiles of dioxin-related
      compounds (DRCs) in breast milk samples from women living in two Vietnamese EWRSs
      and estimated the intake contribution from e-waste-related exposure. Screening
      results using Dioxin-Responsive Chemically Activated LUciferase gene eXpression
      assay (DR-CALUX) showed higher dioxin-like (DL) activities in samples from the
      EWRS Bui Dau than in those from the EWRS Trang Minh and a reference site (2.3-10
      vs 1.7-4.8 and 0.60-5.7 pg CALUX-TEQ/g lipid, n=10, 6 and 9, respectively).
      Chemical analysis results of selected samples show that the WHO-TEQ levels of
      PCDD/Fs, DL-PCBs and PBDD/Fs in EWRS samples were not significantly higher than
      in those from the reference site (0.22-7.4 vs 1.1-3.0 pg/g lipid) and within the
      Vietnamese background range, but women involved in recycling accumulated higher
      concentrations of PCDFs (13-15 vs 2.3-8.8 pg/g lipid) and PBDFs (1.1-1.5 vs <1.1
      pg/g lipid). By comparing the DRC profile in milk of these women with the
      reported profile in house dust from the same site, dust ingestion was estimated
      to contribute most of the intake for tetraBDF, 37 per cent to 55 per cent for
      penta-octaCDFs, but less than twenty per cent for PCDDs and DL-PCBs, and 26 per
      cent for total WHO-TEQs. The DL activities in some EWRS milk samples were not
      fully explained by chemical data, suggesting contribution from unidentified
      compounds. The estimated WHO-TEQ intake doses for breastfed infants (1.3-33
      pg/kg/d) mostly exceeded the tolerable value, especially for those living in the
      EWRSs; and unidentified DRCs might increase further the dioxin-related health
      risk.

PMID- 24859708
TI  - Biochars derived from various crop straws: characterization and Cd(II) removal
      potential.
AB  - Five types of biochars prepared from four crop straws and one wood shaving at 600
      degrees C were characterized, and their sorption to Cd(II) were determined to
      investigate the differences in capacity to function as sorbents to heavy metals.
      Surface areas and pore volumes of the biochars were inversely correlated to the
      lignin content of raw biomass. The biochars derived from crop straws displayed
      more developed pore structure than wood char due to the higher lignin content of
      wood. Sorption capacity of the biochars to Cd(II) followed the order of corn
      straw>cotton straw>wheat straw>rice straw>poplar shaving, which was not strictly
      consistent with the surface area of the chars. The surface characteristics of
      chars before and after Cd(II) sorption were investigated with scanning electron
      microscopy equipped with an energy dispersive X-ray spectroscopy and Fourier
      transform infrared spectroscopy, which suggested that the higher sorption of
      Cd(II) on corn straw chars was mainly attributed to cation exchange, surface
      precipitation of carbonate, and surface complexation with oxygen-containing
      groups. This study indicated that crop straw biochars exhibit distinct sorption
      capacities to heavy metals due to various surface characteristics, and thus the
      sorption efficiency should be carefully evaluated specific to target contaminant.

PMID- 24859709
TI  - The physiological and biochemical effects of salicylic acid on sunflowers
      (Helianthus annuus) exposed to flurochloridone.
AB  - In this study, we comparatively evaluated the effects of the flurochloridone as
      well as flurochloridone and exogenously applied salicylic acid (SA) on Helianthus
      annuus L. to find out herbicide-induced toxicity reducing influence of SA. We
      examined and compared the physiological and biochemical effects of different
      concentrations of flurochloridone (11, 32 and 72 mM) in both the SA pre-treated
      and non-treated plants. The plants treated with flurochloridone exhibited reduced
      total chlorophyll, carotenoid, and relative water content compared to the control
      group, whereas the plants that were pre-treated with SA exhibited relatively
      higher values for the same physiological parameters. In the SA non-treated
      plants, the superoxide dismutase, glutathione reductase and glutathione S
      transferase activities were increased in the treatment groups compared to the
      control group. In the treatment groups, these enzyme activities were decreased in
      the SA-pre-treated plants compared to the non-treated plants. Ascorbate
      peroxidase and catalase activities decreased in the flurochloridone-treated
      plants compared to the control plants. The ascorbate peroxidase activity
      increased in the control groups but decreased in the treatment groups in the SA
      pre-treated plants compared to the non-treated plants. However, SA treatment
      decreased the activity of catalase in the control and treatment groups compared
      to the plants that were not treated with SA. Flurochloridone treatment increased
      the malondialdehyde content in the treated groups compared to the control groups,
      whereas SA-pretreatment decreased malondialdehyde content compared to plants that
      were not treated with SA. Flurochloridone treatment increased endogenous SA
      content compared to the control. Although the residual levels of herbicide in the
      plants increased proportionately with increasing herbicide concentrations, the SA
      pre-treated plants exhibited reduced residual herbicide levels compared to the
      plants that were not treated with SA. These results indicate that the
      flurochloridone induces various physiological and biochemical responses in non
      target plants and that treatment with exogenous SA can increase stress resistance
      by altering these responses.

PMID- 24859710
TI  - Chemosensory mediated behaviors and gene transcription profiles in wild yellow
      perch (Perca flavescens) from metal contaminated lakes.
AB  - The olfactory system of fish is sensitive to the toxic effects of low
      concentrations of contaminants. To investigate the effects of long-term metal
      exposure on olfaction in wild yellow perch (Perca flavescens), fish from one
      clean (Geneva Lake) and two metal-contaminated lakes (Ramsey and Hannah lakes)
      were collected in and around the metal-mining district of Sudbury, ON. Two
      different techniques were used to measure the effects of exposure to
      environmental contamination: (i) behavioral responses were recorded in response
      to conspecific skin extract and (ii) gene transcription differences in olfactory
      rosettes were characterized using a novel, 1000-candidate gene yellow perch
      microarray. Behavioral assays performed on fish from the clean lake demonstrated
      avoidance of a conspecific skin extract, while fish from metal contaminated lakes
      showed no avoidance response. A total of 109 out of the 1000 genes were
      differentially transcribed among the lakes. Most of the differentially
      transcribed genes were between the two metal contaminated lakes relative to
      either of the contaminated lakes and the reference lake. No genes were
      differentially expressed between Geneva Lake (clean) and Hannah Lake (metal
      contaminated). These results demonstrated that even though the different
      populations of fish from both Hannah and Ramey lakes were affected at the
      behavioral level, the impairment of olfaction was not measurable using gene
      transcriptional changes in olfactory rosettes. 

PMID- 24859711
TI  - Lacosamide-induced acute pancreatitis with positive rechallenge test.

PMID- 24859712
TI  - Upper esophageal sphincter abnormalities: frequent finding on high-resolution
      esophageal manometry and associated with poorer treatment response in achalasia.
AB  - BACKGROUND: Abnormalities of the upper esophageal sphincter (UES) on high
      resolution esophageal manometry (HREM) have been observed in both symptomatic and
      asymptomatic individuals and are often interpreted as incidental findings of
      unclear clinical significance. AIMS: Our primary aims were: (1) to assess the
      frequency of UES abnormalities in consecutive patients referred for HREM studies;
      and (2) to characterize the demographics, clinical symptoms, and manometric
      profiles associated with UES abnormalities as compared with those with normal UES
      function. MATERIALS AND METHODS: We performed a retrospective study of 200
      consecutive patients referred for HREM. Patients were divided into those with
      normal and abnormal UES function, including impaired relaxation (residual
      pressure >12 mm Hg), hypertensive (>104 mm Hg), and hypotensive (<34 mm Hg)
      resting pressure. Clinical and manometric profiles were compared. RESULTS: A
      total of 32.5% of patients had UES abnormalities, the majority of which were
      hypertensive (55.4%). Patients with achalasia were significantly more likely to
      have UES abnormalities as compared with normal UES function (57.2% vs. 42.9%,
      P=0.04), with the most frequent abnormality being a hypertensive UES (50%). In
      addition, patients with impaired lower esophageal sphincter (LES) relaxation
      (esophagogastric junction outflow obstruction or achalasia) were more likely to
      have an UES abnormality present as compared with those with normal LES relaxation
      (53.1% vs. 28.6%, P=0.01). When we assessed for treatment response among patients
      with achalasia, we found that subjects with evidence of UES dysfunction had
      significantly worse treatment outcomes as compared with those without UES
      abnormalities present (20% improved vs. 100%, P=0.015). This remained true even
      after adjusting for type of treatment received (surgical myotomy, per-oral
      endoscopic mytotomy, botulinum toxin injection, pneumatic dilatation, medical
      therapy, P=0.67) and achalasia subtype (P=1.00). CONCLUSIONS: UES abnormalities
      are a frequent finding on HREM studies, especially in patients with impaired LES
      relaxation, including both achalasia and esophagogastric junction outflow
      obstruction. Interestingly, the most common UES abnormality associated with
      achalasia was a hypertensive resting UES, despite the fact that achalasia is
      thought to spare striated muscle. Among patients with achalasia, we found a
      significant association between the lack of treatment response and the presence
      of UES dysfunction. The routine evaluation of UES function in patients referred
      for manometry may enhance our understanding of esophageal motility disorders and
      may yield important prognostic information, particularly in subjects with
      achalasia. Future prospective studies are needed to further delineate the
      underlying mechanism between UES dysfunction with achalasia and other esophageal
      motility disorders to predict treatment response and guide therapeutic treatment
      modalities.

PMID- 24859713
TI  - Race and fistulizing perianal Crohn's disease.
AB  - BACKGROUND: There is increasing recognition of Crohn's disease (CD) in non-white
      populations. However, reports of racial disparities in the phenotype of CD are
      still inconsistent. AIM: : The aim of this study was to test the hypothesis that
      African American (AA) patients have higher incidence of severe fistulizing
      perianal Crohn's disease (FPD) compared with white patients. METHODS: Cross
      sectional analysis of 333 adult CD patients treated at The Mount Sinai Hospital
      with infliximab between May 2011 and December 2011 was conducted. Self-reported
      race/ethnicity was recorded and proportions of each group with FPD were compared
      across the population. RESULTS: Among all 333 evaluable CD patients on
      infliximab, 73.6% were white, 11.4% AA, 13.2% Hispanic, and 1.8% Asian. Of these
      333 patients, 88 had FPD: only 48 of these (54.5%) were white, whereas fully 18
      (20.5%) were AA, 20 (22.7%) were Hispanic, and 2 (2.3%) were Asian. Thus,
      patients receiving infliximab for FPD were significantly more likely to be AA or
      Hispanic than white (AA vs. whites: risk ratio=2.63; 95% confidence interval,
      1.74-3.96; P=<0.0001; Hispanics vs. whites: risk ratio=2.32; 95% confidence
      interval, 1.54-3.50; P=0.0001). There was no statistically significant difference
      between AA and Hispanics. CONCLUSION: CD patients at our medical center with FPD
      requiring infliximab therapy were significantly more likely to be AA or Hispanic.

PMID- 24859714
TI  - Predictors for identification of stigmata of recent hemorrhage on colonic
      diverticula in lower gastrointestinal bleeding.
AB  - GOALS: The aim of this study was to identify predictors for the identification of
      stigmata of recent hemorrhage (SRH) on colonic diverticula. BACKGROUND: Several
      factors influence the identification of SRH in the diagnosis of colonic
      diverticular bleeding. STUDY: A total of 396 patients hospitalized for lower
      gastrointestinal bleeding were analyzed. Comorbidities, medications, timing of
      colonoscopy [<24 h (h); urgent, 24 to 48 h, >48 h], preparation, expert
      colonoscopist, use of a cap, use of a water-jet scope, total colonoscopy, and
      procedure time (over 60 min) were assessed. A multivariable logistic regression
      model was used to estimate odds ratio (OR) and 95% confidence interval (CI).
      RESULTS: Two hundred fifteen patients were diagnosed with colonic diverticular
      bleeding and 37 (17%) were identified with SRH. Urgent colonoscopy (OR, 8.4; 95%
      CI, 2.3-30; P<0.01), expert colonoscopist (OR, 3.0; 95% CI, 1.2-7.3; P=0.02), use
      of a cap (OR, 3.4; 95% CI, 1.4-8.0; P=0.01), and use of water-jet scope (OR, 5.8;
      95% CI, 2.3-15; P<0.01) were found to be independent predictive factors for SRH.
      The accuracy of these factors in combination was 0.90 (95% CI, 0.85-0.96) as
      measured by area under the receiver operating characteristic curve (ROC-AUC). SRH
      identification rate was higher in the urgent (22%) than in the 24 to 48 hours
      (2.9%, P<0.01) and >48 hours groups (1.0%, P<0.01), showing a tendency to
      decrease with time (P<0.01 for trend). CONCLUSIONS: Factors of urgent
      colonoscopy, expert colonoscopist, use of a cap, and use of water-jet scope are
      useful for identifying SRH diverticula.

PMID- 24859715
TI  - Current treatment guidelines for chronic hepatitis B and their applications.
AB  - BACKGROUND/AIM: Treatment practices for patients with chronic hepatitis B (CHB)
      varies across the world and several professional associations have issued
      treatment recommendations. This synopsis aims to review the major principles of
      CHB and its management, and to systematically summarize and compare the
      recommendations of the major treatment guidelines by: the Asian-Pacific
      Association for the Study of the Liver, the US Panel, the European Association
      for the Study of the Liver, and the American Association for the Study of the
      Liver. METHODS: Treatment recommendations were summarized separately for
      hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients. CONCLUSIONS:
      Treatment for CHB is recommended on the basis of a variety of host and viral
      factors, and the ultimate goal of treatment is the prevention of decompensated
      liver disease, hepatocellular carcinoma, cirrhosis, and premature death. Despite
      updates and improvements in these guidelines during the past decade, greater
      patient and physician education as well as better noninvasive markers to identify
      high-risk patients are still needed. Significant improvements in the application
      of current practice guidelines, however, can be made by relatively simple
      educational efforts, and new molecular and genomic techniques may hold promise
      for more accurate selection of high-risk patients for further therapeutic
      interventions in a near future.

PMID- 24859716
TI  - Unexpected early retrieval of a fully covered self-expandable metal stent because
      of tissue ingrowth in refractory benign esophageal stricture.

PMID- 24859717
TI  - The use of domperidone increases the completion rate of small bowel capsule
      endoscopy: does this come at the expense of diagnostic yield?
AB  - BACKGROUND: The completion rate (CR) of small bowel capsule endoscopy (SBCE) has
      been reported at 81.3% to 84.8%. Prokinetic agents are used to increase CR and
      (theoretically) diagnostic yield (DY). Domperidone has not been widely used in
      SBCE; unlike metoclopramide, it lacks extrapyramidal adverse effects. OBJECTIVES:
      This was a retrospective study. This study aimed to assess gastric transit time
      (GTT), small bowel transit time (SBTT), and the CR of SBCE when using
      domperidone. Furthermore, we aimed to compare the CR of 2 different SBCE systems
      (MiroCam, PillCam). Consecutive SBCE examinations (January 2008 to October 2012)
      from a tertiary referral center were analyzed. RESULTS: In the aforementioned
      period, a total of 635 SBCE examinations were performed: 379/635 (59.7%) with
      PillCamSB and 256 (40.3%) with MiroCam. In 437/635 (68.8%) examinations, liquid
      domperidone (5 mg) was administered for capsule ingestion, whereas 198 (31.2%)
      ingested the capsule without any domperidone. Although the 2 groups were
      comparable, the median age of patients who received domperidone was higher
      compared with patients who did not receive (58 vs. 48 y, P=0.027). In our cohort,
      the overall CR of SBCE was 88.9%. The 2 SBCE systems showed equivalent CR
      (PillCamSB 88.9%, MiroCam 89.1%; P =0.96). The use of liquid domperidone
      increased CR (91.1% vs. 84.3%; P =0.042). Interestingly, the use of domperidone
      with PillCamSB was associated with reduced DY for vascular, inflammatory, and
      polyps/mass-type lesions. This effect was not seen in the MiroCam group.
      Furthermore, the median GTT and the median SBTT did not differ between the 2
      groups (GTT/SBTT with domperidone 26.0'/221.0' and without 29.0'/228.0',
      respectively; P=0.461/P=0.477). A higher CR was noted when domperidone was used
      with PillCamSB (93.0% vs. 89.5%, P=0.012) than with MiroCam (84.4% vs. 83.3%,
      P=0.08). LIMITATIONS: The major limitations of this study were the retrospective
      design of the study and limited numbers on MiroCam with no domperidone.
      CONCLUSIONS: In conclusion, the use of domperidone increases the CR of SBCE with
      PillCamSB. However, this increase does not translate into higher DY. A smart,
      tailored approach, which may include domperidone, purgatives, and real-time
      viewers, may be used in the clinical practice to improve DY until technology
      delivering capsules with much longer battery time becomes available.

PMID- 24859718
TI  - Balloon mitral valvuloplasty in the United States: a 13-year perspective.
AB  - BACKGROUND: Incidence and prevalence of mitral stenosis is declining in the US.
      We performed this study to determine recent trends in utilization, complications,
      mortality, length of stay, and cost associated with balloon mitral valvuloplasty.
      METHODS: Utilizing the nationwide inpatient sample database from 1998 to 2010, we
      identified patients using the International Classification of Diseases, 9th
      Revision, Clinical Modification procedure code for "percutaneous valvuloplasty."
      Patients >=18 years of age with mitral stenosis were included. Patients with
      concomitant aortic, tricuspid, or pulmonic stenosis were excluded. Primary
      outcome included death and procedural complications. RESULTS: A total of 1308
      balloon mitral valvuloplasties (weighted n = 6540) were analyzed. There was a
      7.5% decrease in utilization of the procedure from 24.6 procedures/10 million
      population in 1998-2001 to 22.7 procedures/10 million population in 2008-2010 (P
      for trend = .098). We observed a 15.9% overall procedural complication rate and
      1.7% mortality rate. The procedural complication rates have increased in recent
      years (P = .001), corresponding to increasing age and burden of comorbidities in
      patients. The mean cost per admission for balloon mitral valvuloplasty has gone
      up significantly over the 10 years, from $11,668 +/- 1046 in 2001 to $23,651 +/-
      301 in 2010 (P <.001). CONCLUSIONS: In a large cross-sectional study of balloon
      mitral valvuloplasty in the US, we have reported trends of decreasing overall
      utilization and increasing procedural complication rates and cost over a period
      of 13 years.

PMID- 24859720
TI  - The drowning heart: an ambiguous lymphoma.

PMID- 24859719
TI  - Patterns of initiation of oral anticoagulants in patients with atrial
      fibrillation- quality and cost implications.
AB  - BACKGROUND: Dabigatran, rivaroxaban, and apixaban have been approved for use in
      patients with atrial fibrillation based upon randomized trials demonstrating
      their comparable or superior efficacy and safety relative to warfarin. Little is
      known about their adoption into clinical practice, whether utilization is
      consistent with the controlled trials on which their approval was based, and how
      their use has affected health spending for patients and insurers. METHODS: We
      used medical and prescription claims data from a large insurer to identify
      patients with nonvalvular atrial fibrillation who were prescribed an oral
      anticoagulant in 2010-2013. We plotted trends in medication initiation over time,
      assessed corresponding insurer and patient out-of-pocket spending, and evaluated
      the cumulative number and cost of anticoagulants. We identified predictors of
      novel anticoagulant initiation using multivariable logistic models. Finally, we
      estimated the difference in total drug expenditures over 6 months for patients
      initiating warfarin versus a novel anticoagulant. RESULTS: There were 6893
      patients with atrial fibrillation that initiated an oral anticoagulant during the
      study period. By the end of the study period, novel anticoagulants accounted for
      62% of new prescriptions and 98% of anticoagulant-related drug costs. Female sex,
      lower household income, and higher CHADS2, CHA2DS2-VASC, and HAS-BLED scores were
      significantly associated with lower odds of receiving a novel anticoagulant (P
      <.001 for each). Average combined patient and insurer anticoagulant spending in
      the first 6 months after initiation was more than $900 greater for patients
      initiating a novel anticoagulant. CONCLUSIONS: This study demonstrates rapid
      adoption of novel anticoagulants into clinical practice, particularly among
      patients with lower CHADS2 and HAS-BLED scores, and high health care cost
      consequences. These findings provide important directions for future comparative
      and cost-effectiveness research.

PMID- 24859721
TI  - Hematuria and urologic malignancies.

PMID- 24859722
TI  - Baseball lingo in the medical world.

PMID- 24859723
TI  - Development and application of site mapping methods for the design of
      glycosaminoglycans.
AB  - Glycosaminoglycans (GAGs) are complex polysaccharides involved in a wide range of
      biological signaling events, as well as being important as biological structural
      materials. Despite the ubiquity and importance of GAG-protein interactions in
      biological systems and potentially as therapeutic targets, detailed structures of
      such interactions are sparse in availability. Computational methods can provide
      detailed structural knowledge of these interactions; however, they should be
      evaluated against suitable test systems prior to their widespread use. In this
      study, we have investigated the application of automated molecular docking and
      interaction mapping techniques to characterizing GAG-protein interactions. A
      series of high-resolution X-ray crystal structures of GAGs in complex with
      proteins was used to evaluate the approaches. Accurately scoring the pose fitting
      best with the crystal structure was a challenge for all docking programs
      evaluated. The site mapping technique offered excellent prediction of the key
      residues involved in ligand recognition, comparable to the best pose and improved
      over the top-ranked pose. A design protocol incorporating site- and ligand-based
      mapping techniques was developed and applied to identify GAGs capable of binding
      to acidic fibroblast growth factor (aFGF). The protocol was able to identify
      ligands known to bind to aFGF and accurately able to predict the binding modes of
      those ligands when using a known ligand-binding conformation of the protein. This
      study demonstrates the value of mapping-based techniques in identifying specific
      GAG epitopes recognized by proteins and for GAG-based drug design. 

PMID- 24859725
TI  - Creation and implementation of department-wide structured reports: an analysis of
      the impact on error rate in radiology reports.
AB  - The purpose of this study was to evaluate and compare textual error rates and
      subtypes in radiology reports before and after implementation of department-wide
      structured reports. Randomly selected radiology reports that were generated
      following the implementation of department-wide structured reports were evaluated
      for textual errors by two radiologists. For each report, the text was compared to
      the corresponding audio file. Errors in each report were tabulated and
      classified. Error rates were compared to results from a prior study performed
      prior to implementation of structured reports. Calculated error rates included
      the average number of errors per report, average number of nongrammatical errors
      per report, the percentage of reports with an error, and the percentage of
      reports with a nongrammatical error. Identical versions of voice-recognition
      software were used for both studies. A total of 644 radiology reports were
      randomly evaluated as part of this study. There was a statistically significant
      reduction in the percentage of reports with nongrammatical errors (33 to 26%; p =
      0.024). The likelihood of at least one missense omission error (omission errors
      that changed the meaning of a phrase or sentence) occurring in a report was
      significantly reduced from 3.5 to 1.2% (p = 0.0175). A statistically significant
      reduction in the likelihood of at least one comission error (retained statements
      from a standardized report that contradict the dictated findings or impression)
      occurring in a report was also observed (3.9 to 0.8%; p = 0.0007). Carefully
      constructed structured reports can help to reduce certain error types in
      radiology reports.

PMID- 24859724
TI  - Glyco-variant library of the versatile enzyme horseradish peroxidase.
AB  - When the glycosylated plant enzyme horseradish peroxidase (HRP) is conjugated to
      specific antibodies, it presents a powerful tool for medical applications. The
      isolation and purification of this enzyme from plant is difficult and only gives
      low yields. However, HRP recombinantly produced in the yeast Pichia pastoris
      experiences hyperglycosylation, which impedes the use of this enzyme in medicine.
      Enzymatic and chemical deglycosylation are cost intensive and cumbersome and
      hitherto existing P. pastoris strain engineering approaches with the goal to
      avoid hyperglycosylation only resulted in physiologically impaired yeast strains
      not useful for protein production processes. Thus, the last resort to obtain less
      glycosylated recombinant HRP from P. pastoris is to engineer the enzyme itself.
      In the present study, we mutated all the eight N-glycosylation sites of HRP C1A.
      After determination of the most suitable mutation at each N-glycosylation site,
      we physiologically characterized the respective P. pastoris strains in the
      bioreactor and purified the produced HRP C1A glyco-variants. The biochemical
      characterization of the enzyme variants revealed great differences in catalytic
      activity and stability and allowed the combination of the most promising
      mutations to potentially give an unglycosylated, active HRP C1A variant useful
      for medical applications. Interestingly, site-directed mutagenesis proved to be a
      valuable strategy not only to reduce the overall glycan content of the
      recombinant enzyme but also to improve catalytic activity and stability. In the
      present study, we performed an integrated bioprocess covering strain generation,
      bioreactor cultivations, downstream processing and product characterization and
      present the biochemical data of the HRP glyco-library. 

PMID- 24859726
TI  - Detection of quiescent cardiac phases in echocardiography data using nonlinear
      filtering and boundary detection techniques.
AB  - We describe an algorithm to detect cardiac quiescence within a heartbeat using
      nonlinear filtering and boundary detection techniques in echocardiography images.
      The motivation for detection of these quiescent phases is to provide improved
      cardiac gating to obtain motion-artifact-free images of the heart at cardiac
      computed tomography (CT). Currently, cardiac gating is provided through
      electrocardiography (ECG), which does not provide information about the
      instantaneous mechanical state of the heart. Our goal is to test if information
      about the actual mechanical motion of the heart obtained from B-mode
      echocardiographic data could potentially be used for gating purposes. The
      nonlinear filtering algorithm presented involves anisotropic diffusion to
      smoothen the homogeneous regions of the B-mode images while preserving image
      edges that represent myocardial boundaries. Following this, we detect the
      boundary of a particular region of interest (ROI) using a thresholding step. The
      positional changes of this ROI are then observed for quiescent phases over
      multiple cardiac cycles using the ECG's R-R interval. In a pilot study, seven
      subjects were imaged in the apical, four-chamber view, and quiescence of the
      interventricular septum was primarily observed in the diastolic region of the ECG
      signal. However, the position and length of quiescence vary across multiple
      heartbeats for the same individual and for different individuals as well. The
      center of quiescence for the seven patients ranged from 51 to 84 % and did not
      show a trend with heart rates, which ranged from 54 to 83 beats per minute. The
      gating intervals based on such analysis of echocardiographic signals could
      potentially optimize cardiac CT gating. 

PMID- 24859729
TI  - Vitamin D and gestational diabetes: an update.
AB  - PURPOSE OF REVIEW: Vitamin D status (which is involved in glucose homeostasis) is
      related to gestational diabetes mellitus (GDM). GDM is characterized by increased
      resistance to and impaired secretion of insulin and results in higher risk of
      adverse pregnancy outcomes including operative delivery, macrosomia, shoulder
      dystocia and neonatal hypoglycemia. Women with GDM and their babies are at
      increased risk for developing type II diabetes. RECENT FINDINGS: International
      definitions of vitamin D deficiency and normality are inconsistent. Vitamin D
      deficiency is common in pregnant women particularly those with poor diets and who
      have dark skins living in temperate climes with lack of exposure to sunlight.
      SUMMARY: Few interventional studies indicate that supplementation optimizes
      maternal vitamin D status or improves maternal glucose metabolism. Observational
      studies about maternal vitamin D status and risk of GDM are conflicting. This
      could be because of measurement of vitamin D or differences in population
      characteristics such as ethnicity, geographic location, gestational age at
      sampling and diagnostic criteria for GDM. Good-quality randomized controlled
      trials are required to determine whether vitamin D supplementation decreases the
      risk of GDM or improves glucose tolerance in diabetic women.

PMID- 24859728
TI  - Comparative analysis of metabolic proteome variation in ascorbate-primed and
      unprimed wheat seeds during germination under salt stress.
AB  - Seed priming with ascorbic acid improves salt tolerance in durum wheat. For
      understanding the potential mechanisms underlying this priming effect a gel-free
      shotgun proteomic analysis was performed comparing unprimed to ascorbate-primed
      wheat seed during germination under saline and non-saline conditions. Since seed
      germination is the result of interplay or cross-talk between embryo and embryo
      surrounding tissues, we studied the variation of metabolic proteome in both
      tissues separately. 167 of 697 identified and 69 of 471 identified proteins
      increase or decrease in abundance significantly in response to priming and/or
      salinity compared to untreated, unstressed control in embryo and embryo
      surrounding tissues, respectively. In untreated wheat embryo salt stress was
      accompanied by change in 129 proteins, most of which are belonging to metabolism,
      energy, disease/defense, protein destination and storage categories. Ascorbate
      pretreatment prevents and counteracts the effects of salinity upon most of these
      proteins and changes specifically the abundance of 35 others proteins, most of
      which are involved in metabolism, protein destination and storage categories.
      Hierarchical clustering analysis revealed three and two major clusters of protein
      expression in embryo and embryo-surrounding tissues, respectively. This study
      opens promising new avenues to understand priming-induced salt tolerance in
      plants. BIOLOGICAL SIGNIFICANCE: To clearly understand how ascorbate-priming
      enhance the salt tolerance of durum wheat during germination, we performed for
      the first time a comparative shotgun proteomic analysis between unprimed and
      ascorbate-primed wheat seeds during germination under saline and non-saline
      conditions. Furthermore, since seed germination is the result of interplay or
      cross-talk between embryo and embryo-surrounding tissues we analyzed the
      variation of metabolic proteome in both tissues separately. 1168 proteins
      exhibiting greater molecular weight diversity (ranging from 5 to 258kDa) were
      identified. Among them, 167 and 69 proteins were increased or decreased in
      abundance significantly by priming and/or salinity as compared to control, in
      embryo and embryo-surrounding tissues respectively. Ascorbate pretreatment
      alleviates the effects of salinity upon most of these proteins, particularly
      those involved in metabolism, energy, disease/defense, protein destination and
      storage functions. Hierarchical clustering analysis revealed three and two major
      clusters of protein accumulation in embryo and embryo-surrounding tissues,
      respectively. These results may provide new avenues for understanding and
      advancing priming-induced salt tolerance in crop plants.

PMID- 24859727
TI  - Identification and quantification of the basal and inducible Nrf2-dependent
      proteomes in mouse liver: biochemical, pharmacological and toxicological
      implications.
AB  - The transcription factor Nrf2 is a master regulator of cellular defence: Nrf2
      null mice (Nrf2((-/-))) are highly susceptible to chemically induced toxicities.
      We report a comparative iTRAQ-based study in Nrf2((-/-)) mice treated with a
      potent inducer, methyl-2-cyano-3,12-dioxooleana-1,9(11)dien-28-oate (CDDO-me;
      bardoxolone -methyl), to define both the Nrf2-dependent basal and inducible
      hepatoproteomes. One thousand five hundred twenty-one proteins were fully
      quantified (FDR <1%). One hundred sixty-one were significantly different (P<0.05)
      between WT and Nrf2((-/-)) mice, confirming extensive constitutive regulation by
      Nrf2. Treatment with CDDO-me (3mg/kg; i.p.) resulted in significantly altered
      expression of 43 proteins at 24h in WT animals. Six proteins were regulated at
      both basal and inducible levels exhibiting the largest dynamic range of Nrf2
      regulation: cytochrome P4502A5 (CYP2A5; 17.2-fold), glutathione-S-transferase-Mu
      3 (GSTM3; 6.4-fold), glutathione-S-transferase Mu 1 (GSTM1; 5.9-fold),
      ectonucleoside-triphosphate diphosphohydrolase (ENTPD5; 4.6-fold), UDP-glucose-6
      dehydrogenase (UDPGDH; 4.1-fold) and epoxide hydrolase (EPHX1; 3.0-fold). These
      proteins, or their products, thus provide a potential source of biomarkers for
      Nrf2 activity. ENTPD5 is of interest due to its emerging role in AKT signalling
      and, to our knowledge, this protein has not been previously shown to be Nrf2
      dependent. Only two proteins altered by CDDO-me in WT animals were similarly
      affected in Nrf2((-/-)) mice, demonstrating the high degree of selectivity of
      CDDO-me for the Nrf2:Keap1 signalling pathway. BIOLOGICAL SIGNIFICANCE: The
      Nrf2:Keap1 signalling pathway is attracting considerable interest as a
      therapeutic target for different disease conditions. For example, CDDO-me
      (bardoxolone methyl) was investigated in clinical trials for the treatment of
      acute kidney disease, and dimethyl fumarate, recently approved for reducing
      relapse rate in multiple sclerosis, is a potent Nrf2 inducer. Such compounds have
      been suggested to act through multiple mechanisms; therefore, it is important to
      define the selectivity of Nrf2 inducers to assess the potential for off-target
      effects that may lead to adverse drug reactions, and to provide biomarkers with
      which to assess therapeutic efficacy. Whilst there is considerable information on
      the global action of such inducers at the mRNA level, this is the first study to
      catalogue the hepatic protein expression profile following acute exposure to CDDO
      me in mice. At a dose shown to evoke maximal Nrf2 induction in the liver, CDDO-me
      appeared highly selective for known Nrf2-regulated proteins. Using the transgenic
      Nrf2((-/-)) mouse model, it could be shown that 97% of proteins induced in wild
      type mice were associated with a functioning Nrf2 signalling pathway. This
      analysis allowed us to identify a panel of proteins that were regulated both
      basally and following Nrf2 induction. Identification of these proteins, which
      display a large magnitude of variation in their expression, provides a rich
      source of potential biomarkers for Nrf2 activity for use in experimental animals,
      and which may be translatable to man to define individual susceptibility to
      chemical stress, including that associated with drugs, and also to monitor the
      pharmacological response to Nrf2 inducers.

PMID- 24859730
TI  - Effects of vitamin a status on expression of ucp1 and brown/beige adipocyte
      related genes in white adipose tissues of beef cattle.
AB  - We previously reported the presence of brown/beige adipocytes in the white fat
      depots of mature cattle. The present study examined the effects of dietary
      vitamin A on the expression of brown/beige adipocyte-related genes in the white
      fat depots of fattening cattle. No significant differences were observed in the
      expression of Ucp1 between vitamin A-deficient cattle and control cattle.
      However, the expression of the other brown/beige adipocyte-related genes was
      slightly higher in the mesenteric fat depots of vitamin A-deficient cattle. The
      present results suggest that a vitamin A deficiency does not markedly affect the
      expression of Ucp1 in white fat depots, but imply that it may stimulate the
      emergence of beige adipocytes in the mesenteric fat depots of fattening cattle. 

PMID- 24859731
TI  - Difference in knee rotation between total and unicompartmental knee
      arthroplasties during stair climbing.
AB  - PURPOSE: The purpose of this study was to compare knee kinematics during stair
      walking in patients with simultaneous total knee arthroplasty (TKA) and
      unicompartmental knee arthroplasties (UKA). It was hypothesized that UKA would
      reproduce more normalized knee kinematics than TKA during stair ascent and
      descent. METHODS: Six patients who received UKA in one knee and TKA in the other
      knee were included in the study. For this study, a four-step staircase was
      assembled with two force platforms being positioned at the centre of the second
      and third steps. Each patient was attached with 16 reflective markers at both
      lower extremities and was asked to perform five roundtrip trials of stair
      climbing. Kinematic parameters including stance duration, knee angle, vertical
      ground reaction force (GRF), joint reaction force, and moments were obtained and
      analysed using a10-camera motion system (VICON, Oxford, UK). Nonparametric
      Friedman test was used to compare the results between two arthroplasty methods
      and between stair ascent and descent. RESULTS: Compared to TKA, UKA knees
      exhibited significantly greater degree of rotation in transverse planes (5.0
      degrees during ascent and 6.0 degrees during descent on average), but showed no
      difference in terms of the other parameters. When comparing the results during
      stair ascent with descent, overall greater knee angle, vertical GRF, joint
      reaction force, and moment were observed during stair descent. CONCLUSIONS: Both
      UKA and TKA knees have shown overall similar knee kinematics, though UKA knee may
      allow greater degree of rotation freedom, which resembles normal knee kinematics
      during stair walking.

PMID- 24859732
TI  - A qualitative and quantitative analysis of the attachment sites of the proximal
      hamstrings.
AB  - PURPOSE: Proximal hamstring tears represent a challenge. Surgical repair of such
      tears has been reported utilizing both open and endoscopic techniques. It was
      hypothesized that the proximal attachments of the hamstring muscle group could be
      reproducibly and consistently measured from pertinent bony anatomical reference
      landmarks. METHODS: Fourteen fresh-frozen, human cadaveric specimens were
      dissected, and measurements were taken regarding the proximal attachments of the
      hamstring muscle group in reference to bony landmarks. A highly precise
      coordinate measuring device was used for three-dimensional measurements of tendon
      footprints and bony landmarks, and relevant distances between structures were
      calculated. RESULTS: The semitendinosus and long head of the biceps femoris
      shared a proximal origin (conjoined tendon), having an oval footprint with an
      average area of 567.0 mm(2) [95 % CI 481.0-652.9]. The semimembranosus (SM)
      footprint was crescent-shaped and located anterolateral to the conjoined tendon,
      with an average area of 412.4 mm(2) [95 % CI 371.0-453.8]. The SM footprint had
      an accessory tendinous extension that extended anteromedially forming a distinct
      footprint. A consistent bony landmark was found at the medial ischial margin,
      14.6 mm [95 % CI 12.7-16.5] from the centre of the conjoined tendon footprint,
      which coincided with the distal insertion of the sacrotuberous ligament.
      CONCLUSION: The conjoined tendon was the largest attachment of the proximal
      hamstring group. Two other distinct attachment footprints were identified as the
      SM footprint and the accessory tendinous extension. The sacrotuberous ligament
      insertion served as a bony landmark. The anatomical data established in this
      study may aid in better restoring the anatomy during repair of proximal hamstring
      tears.

PMID- 24859734
TI  - Talipes equinovarus (clubfoot): neglected for 47 years and subsequent treatment.

PMID- 24859733
TI  - Successful non-operative management of spontaneous type II gallbladder
      perforation in a patient with Alzheimer's disease.
AB  - A 77-year-old man with Alzheimer's disease was admitted to a rural hospital in
      June 2012 and an acute cholecistytis was first diagnosed. Surgery was not
      considered as a possible option due to the critical condition of the patient and
      his severe comorbidities. After 2 days of broad-spectrum antibiotics, the patient
      worsened and developed severe sepsis. A gallbladder perforation with intrahepatic
      abscess formation was diagnosed on ultrasonography (US) and abdominal CT scan.
      The patient underwent percutaneous US-guided gallbladder drainage with resolution
      of the sepsis and rapid clinical improvement. After 1 month, the drainage was
      removed and the patient was discharged. He survived in good condition for 18
      months and he passed away from pneumonitis in December 2013. This case shows that
      in a case of acute cholecystitis with gallbladder perforation, percutaneous
      gallbladder drainage can be a lifesaving procedure in elderly patients with
      severe comorbidities (including Alzheimer's disease) who are not candidates for
      elective surgery. 

PMID- 24859735
TI  - Influenza knowledge, attitude, and behavior survey for grade school students:
      design and novel assessment methodology.
AB  - Despite the fact infectious diseases can spread readily in grade schools, few
      studies have explored prevention in this setting. Additionally, we lack valid
      tools for students to self-report knowledge, attitudes, and behaviors. As part of
      an ongoing study of a curriculum intervention to promote healthy behaviors, we
      developed and evaluated age-appropriate surveys to determine students'
      understanding of influenza prevention. Surveys were adapted from adolescent and
      adult influenza surveys and administered to students in grades 2-5 (ages 7-11) at
      two Rochester public schools. We assessed student understanding by analyzing
      percent repeatability of 20 survey questions and compared percent "don't know"
      (DK) responses across grades, gender, and race. Questions thought to be ambiguous
      after early survey administration were investigated in student focus groups,
      modified as appropriate, and reassessed. The response rate across all surveys was
      >87%. Survey questions were well understood; 16 of 20 questions demonstrated
      strong pre/post repeatability (>70%). Only 1 question showed an increase in DK
      response for higher grades (p < .0001). Statistical analysis and qualitative
      feedback led to modification of 3 survey questions and improved measures of
      understanding in the final survey administration. Grade-school students'
      knowledge, attitudes and behavior toward influenza prevention can be assessed
      using surveys. Quantitative and qualitative analysis may be used to assess
      participant understanding and refine survey development for pediatric survey
      instruments. These methods may be used to assess the repeatability and validity
      of surveys to assess the impact of health education interventions in young
      children.

PMID- 24859736
TI  - Knowledge and beliefs of African-American and American Indian parents and
      supporters about infant safe sleep.
AB  - To investigate, by using qualitative methods, beliefs among African-American and
      American Indian families about infant safe sleep practices, barriers to
      acceptance of prevention recommendations, and more effective messaging
      strategies. Seventy-three mothers and supporters participated in focus groups.
      Participants discussed infant sleep practices and effectiveness of safe sleep
      messages. Data were coded, and themes were developed and revised in an iterative
      manner as patterns became more apparent. Themes included reasons for and
      influences on sleep decisions, and concerns about safe sleep recommendations.
      Parental sleep decisions seemed to be driven by perceptions of what would make
      their infant most comfortable and safe, and what would be most convenient.
      Parents were aware of safe sleep recommendations but unaware of the rationale.
      Because they generally did not believe that their infants were at risk for a
      sleep-related death, day-to-day decisions seemed to focus on what was most
      effective in getting their infant to sleep. There appeared to be no distinctions
      in opinions among African-American and American Indian families. African-American
      and American Indian families seemed to have similar concerns about infant comfort
      and safety, and their perceptions about what would be most effective in achieving
      these goals appeared to be important influences on their sleep practices.
      Adherence with safe sleep recommendations may be enhanced if health care
      providers and educational materials discussed rationale underlying
      recommendations and addressed common parental concerns. It may be beneficial to
      target educational interventions towards fathers, as they may be untapped sources
      in implementing safe sleep practices. 

PMID- 24859737
TI  - HDL inhibits the effects of oxidized phospholipids on endothelial cell gene
      expression via multiple mechanisms.
AB  - Oxidized 1-palmitoyl-2-arachidonyl-sn-glycero-3-phospholcholine (OxPAPC) and its
      component phospholipids accumulate in atherosclerotic lesions and regulate the
      expression of >1,000 genes, many proatherogenic, in human aortic endothelial
      cells (HAECs). In contrast, there is evidence in the literature that HDL protects
      the vasculature from inflammatory insult. We have previously shown that in HAECs,
      HDL attenuates the expression of several proatherogenic genes regulated by OxPAPC
      and 1-palmitoyl-2-(5,6-epoxyisoprostane E2)-sn-glycero-3-phosphocholine. We now
      demonstrate that HDL reverses >50% of the OxPAPC transcriptional response. Genes
      reversed by HDL are enriched for inflammatory and vascular development pathways,
      while genes not affected by HDL are enriched for oxidative stress response
      pathways. The protective effect of HDL is partially mimicked by cholesterol
      repletion and treatment with apoA1 but does not require signaling through
      scavenger receptor class B type I. Furthermore, our data demonstrate that HDL
      protection requires direct interaction with OxPAPC. HDL-associated platelet
      activating factor acetylhydrolase (PAF-AH) hydrolyzes short-chain bioactive
      phospholipids in OxPAPC; however, inhibiting PAF-AH activity does not prevent HDL
      protection. Our results are consistent with HDL sequestering specific bioactive
      lipids in OxPAPC, thereby preventing their regulation of select target genes.
      Overall, this work implicates HDL as a major regulator of OxPAPC action in
      endothelial cells via multiple mechanisms. 

PMID- 24859738
TI  - To hydrolyze or not to hydrolyze: the dilemma of platelet-activating factor
      acetylhydrolase.
AB  - Mounting ambiguity persists around the functional role of the plasma form of
      platelet-activating factor acetylhydrolase (PAF-AH). Because PAF-AH hydrolyzes
      PAF and related oxidized phospholipids, it is widely accepted as an anti
      inflammatory enzyme. On the other hand, its actions can also generate
      lysophosphatidylcholine (lysoPC), a component of bioactive atherogenic oxidized
      LDL, thus allowing the enzyme to have proinflammatory capabilities. Presence of a
      canonical lysoPC receptor has been seriously questioned for a multitude of
      reasons. Animal models of inflammation show that elevating PAF-AH levels is
      beneficial and not deleterious and overexpression of PAF receptor (PAF-R) also
      augments inflammatory responses. Further, many Asian populations have a
      catalytically inert PAF-AH that appears to be a severity factor in a range of
      inflammatory disorders. Correlation found with elevated levels of PAF-AH and CVDs
      has led to the design of a specific PAF-AH inhibitor, darapladib. However, in a
      recently concluded phase III STABILITY clinical trial, use of darapladib did not
      yield promising results. Presence of structurally related multiple ligands for
      PAF-R with varied potency, existence of multi-molecular forms of PAF-AH, broad
      substrate specificity of the enzyme and continuous PAF production by the so
      called bi-cycle of PAF makes PAF more enigmatic. This review seeks to address the
      above concerns. 

PMID- 24859740
TI  - Soft drink that claims to burn 200 calories a can is referred to trading
      standards.

PMID- 24859739
TI  - Enhanced synthesis of saturated phospholipids is associated with ER stress and
      lipotoxicity in palmitate treated hepatic cells.
AB  - High levels of saturated FAs (SFAs) are acutely toxic to a variety of cell types,
      including hepatocytes, and have been associated with diseases such as type 2
      diabetes and nonalcoholic fatty liver disease. SFA accumulation has been
      previously shown to degrade endoplasmic reticulum (ER) function leading to other
      manifestations of the lipoapoptotic cascade. We hypothesized that dysfunctional
      phospholipid (PL) metabolism is an initiating factor in this ER stress response.
      Treatment of either primary hepatocytes or H4IIEC3 cells with the SFA palmitate
      resulted in dramatic dilation of the ER membrane, coinciding with other markers
      of organelle dysfunction. This was accompanied by increased de novo glycerolipid
      synthesis, significant elevation of dipalmitoyl phosphatidic acid,
      diacylglycerol, and total PL content in H4IIEC3 cells. Supplementation with
      oleate (OA) reversed these markers of palmitate (PA)-induced lipotoxicity. OA/PA
      cotreatment modulated the distribution of PA between lipid classes, increasing
      the flux toward triacylglycerols while reducing its incorporation into PLs.
      Similar trends were demonstrated in both primary hepatocytes and the H4IIEC3
      hepatoma cell line. Overall, these findings suggest that modifying the FA
      composition of structural PLs can protect hepatocytes from PA-induced ER stress
      and associated lipotoxicity.

PMID- 24859741
TI  - Increase in heart failure mortality in Poland: can we explain the reasons?

PMID- 24859742
TI  - Increase in heart failure mortality in Poland: can we explain the reasons?
      Author's reply.

PMID- 24859743
TI  - Delivery of proteins to mammalian cells via gold nanoparticle mediated laser
      transfection.
AB  - Nanoparticle laser interactions are in widespread use in cell manipulation. In
      particular, molecular medicine needs techniques for the directed delivery of
      molecules into mammalian cells. Proteins are the final mediator of most cellular
      cascades. However, despite several methodical approaches, the efficient delivery
      of proteins to cells remains challenging. This paper presents a new protein
      transfection technique via laser scanning of cells previously incubated with gold
      nanoparticles. The laser-induced plasmonic effects on the gold nanoparticles
      cause a transient permeabilization of the cellular membrane, allowing proteins to
      enter the cell. Applying this technique, it was possible to deliver green
      fluorescent protein into mammalian cells with an efficiency of 43%, maintaining a
      high level of cell viability. Furthermore, a functional delivery of Caspase 3, an
      apoptosis mediating protein, was demonstrated and evaluated in several cellular
      assays. Compared to conventional protein transfection techniques such as
      microinjection, the methodical approach presented here enables high-throughput
      transfection of about 10 000 cells per second. Moreover, a well-defined point in
      time of delivery is guaranteed by gold nanoparticle mediated laser transfection,
      allowing the detailed temporal analysis of cellular pathways and protein
      trafficking.

PMID- 24859744
TI  - Cardiac energetics analysis after aortic valve replacement with 16-mm ATS
      mechanical valve.
AB  - The 16-mm ATS mechanical valve is one of the smallest prosthetic valves used for
      aortic valve replacement (AVR) in patients with a very small aortic annulus, and
      its clinical outcomes are reportedly satisfactory. Here, we analyzed the left
      ventricular (LV) performance after AVR with the 16-mm ATS mechanical valve, based
      on the concept of cardiac energetics analysis. Eleven patients who underwent AVR
      with the 16-mm ATS mechanical valve were enrolled in this study. All underwent
      echocardiographic examination at three time points: before AVR, approximately 1
      month after AVR, and approximately 1 year after AVR. LV contractility (end
      systolic elastance [Ees]), afterload (effective arterial elastance [Ea]), and
      efficiency (ventriculoarterial coupling [Ea/Ees] and the stroke work to pressure
      volume area ratio [SW/PVA]) were noninvasively measured by echocardiographic data
      and blood pressure measurement. Ees transiently decreased after AVR and then
      recovered to the pre-AVR level at the one-year follow-up. Ea significantly
      decreased in a stepwise manner. Consequently, Ea/Ees and SW/PVA were also
      significantly improved at the one-year follow-up compared with those before AVR.
      The midterm LV performance after AVR with the 16-mm ATS mechanical valve was
      satisfactory. AVR with the 16-mm ATS mechanical valve is validated as an
      effective treatment for patients with a very small aortic annulus. The cardiac
      energetics variables, coupling with the conventional hemodynamic variables, can
      contribute to a better understanding of the patients' clinical conditions, and
      those may serve as promising indices of the cardiac function. 

PMID- 24859745
TI  - Thanatophoric dysplasia. Correlation among bone X-ray morphometry,
      histopathology, and gene analysis.
AB  - OBJECTIVE: Documentation through X-ray morphometry and histology of the steady
      phenotype expressed by FGFR3 gene mutation and interpolation of mechanical
      factors on spine and long bones dysmorphism. MATERIALS AND METHODS: Long bones
      and spine of eight thanatophoric dysplasia and three age-matched controls without
      skeletal dysplasia were studied after pregnancy termination between the 18th and
      the 22nd week with X-ray morphometry, histology, and molecular analysis.
      Statistical analysis with comparison between TD cases and controls and
      intraobserver/interobserver variation were applied to X-ray morphometric data.
      RESULTS: Generalized shortening of long bones was observed in TD. A variable
      distribution of axial deformities was correlated with chondrocyte proliferation
      inhibition, defective seriate cell columns organization, and final formation of
      the primary metaphyseal trabeculae. The periosteal longitudinal growth was not
      equally inhibited, so that decoupling with the cartilage growth pattern produced
      the typical lateral spurs around the metaphyseal growth plates. In spine,
      platyspondyly was due to a reduced height of the vertebral body anterior
      ossification center, while its enlargement in the transversal plane was not
      restricted. The peculiar radiographic and histopathological features of TD bones
      support the hypothesis of interpolation of mechanical factors with FGFR3 gene
      mutations. CONCLUSIONS: The correlated observations of X-ray morphometry,
      histopathology, and gene analysis prompted the following diagnostic workup for
      TD: (1) prenatal sonography suspicion of skeletal dysplasia; (2) post-mortem X
      ray morphometry for provisional diagnosis; (3) confirmation by genetic tests (hot
      spot exons 7, 10, 15, and 19 analysis with 80-90% sensibility); (4) in negative
      cases if histopathology confirms TD diagnosis, research of rare mutations through
      sequential analysis of FGFR3 gene.

PMID- 24859746
TI  - Dysfunctional Wnt/beta-catenin signaling contributes to blood-brain barrier
      breakdown in Alzheimer's disease.
AB  - Increased Abeta clearance from brain is essential for restoring the pathological
      manifestation of Alzheimer's disease (AD) and attenuating the cognitive disorder.
      The blood-brain barrier (BBB) plays a critical role in maintaining homeostasis of
      the brain, and transporters e.g. P-glycoprotein (P-gp) are essential for Abeta
      clearance from the brain. In addition, the Wnt/beta-catenin signaling pathway
      contributes to BBB formation, induction and maturation, and induces BBB function.
      Dysfunctional Wnt/beta-catenin signaling in the BBB reveals the importance of
      this pathway, since this contributes to the neurodegeneration characteristic of
      AD. Based on the above evidence, we propose that targeting the canonical Wnt
      signaling pathway could be promising therapeutic approach for treatment of AD. 

PMID- 24859747
TI  - Targeting apoptosis for anticancer therapy.
AB  - Programmed cell death via apoptosis is characteristically disturbed in human
      cancers. This facilitates not only tumor formation and progression, but also
      treatment resistance. Since many currently applied anticancer treatment
      strategies rely on intact cell death signaling pathways for their therapeutic
      efficacy, a better understanding of the regulatory mechanisms that control cell
      death signaling pathways is critical to bypass resistance. Thus, reactivation of
      cell death programs in cancer cells may open new perspectives for more effective
      and more tumor-selective, yet less toxic anticancer therapies. 

PMID- 24859748
TI  - Harnessing the exosome-induced immune response for cancer immunotherapy.
AB  - In recent years exosomes have emerged as potent stimulators of immune responses
      and as agents for cancer therapy. Exosomes can carry a broad variety of
      immunostimulatory molecules depending on the cell of origin and in vitro culture
      conditions. Dendritic cell-derived exosomes (dexosomes) have been shown to carry
      NK cell activating ligands and can be loaded with antigen to activate invariant
      NKT cells and to induce antigen-specific T and B cell responses. Dexosomes have
      been investigated as therapeutic agents against cancer in two phase I clinical
      trials, with a phase II clinical trial currently ongoing. Dexosomes were well
      tolerated but therapeutic success and immune activation were limited. Several
      reports suggest that multiple factors need to be considered in order to improve
      exosomal immunogenicity for cancer immunotherapy. These include antigen-loading
      strategies, exosome composition and exosomal trafficking in vivo. Hence, a better
      understanding of how to engineer and deliver exosomes to specific cells is
      crucial to generate strong immune responses and to improve the immunotherapeutic
      potential of exosomes. 

PMID- 24859750
TI  - Sleep onset is disrupted following pre-sleep exercise that causes large
      physiological excitement at bedtime.
AB  - PURPOSE: Many studies have failed to show that pre-sleep exercise has a negative
      effect on sleep onset. However, since only a moderate level of physiological
      excitement was observed at bedtime in these studies, it remains unclear whether a
      larger magnitude of physiologic excitement present at bedtime would disrupt sleep
      onset. This study compared the effects of pre-sleep exercise, which led to
      different levels of physiologic excitement at bedtime (moderate and heavy), on
      sleep onset. METHODS: Twelve active young men underwent non-exercise, moderate
      intensity exercise, and high-intensity exercise conditions. The subjects
      maintained a sedentary condition on a reclining seat throughout the day. On the
      non-exercise day, the subjects remained seated at rest until going to bed. On the
      moderate- and high-intensity exercise days, the subject exercised for 40 min
      (21:20-22:00) at 60 and 80% heart rate reserve, respectively. Sleep
      polysomnography, core body and skin temperatures, heart rate (HR), and heart rate
      variability (HRV) were recorded. RESULTS: We observed a delay in sleep onset
      (+14.0 min, P < 0.05), a marked physiological excitement at bedtime as reflected
      by an increased HR (+25.7 bpm, P < 0.01), and a lower high-frequency power of HRV
      (-590 ms(2), P < 0.01) only on the high-intensity exercise day. CONCLUSIONS:
      These results indicate that pre-sleep vigorous exercise, which causes a large
      physiologic excitement at bedtime, might disrupt the onset of sleep.

PMID- 24859751
TI  - Heat exposure in female rats elicits abnormal fear expression and cellular
      changes in prefrontal cortex and hippocampus.
AB  - Despite a twofold higher prevalence of fear-related disorders in women, the
      neurobiological factors that modulate and drive fear expression are rarely
      studied in female animals. Fear conditioning and extinction are useful tools for
      dissecting these mechanisms, and here we tested the effects of environmental
      manipulations - four days of exposure to 31 degrees C temperatures in the animal
      housing facility - on fear learning and memory exclusively in female rats. We
      found that heat exposure disrupted freezing to tone during fear conditioning, and
      elicited enhanced freezing during extinction and extinction retrieval. We also
      performed immunohistochemistry for c-fos expression in the infralimbic (IL) and
      prelimbic (PL) regions of the prefrontal cortex during extinction retrieval, and
      found that heat exposure induced a switch from IL-dominated activity to PL
      dominated activity. Finally, morphological analysis of spines in hippocampal CA3
      neurons revealed an increase in spine head diameter in heat-exposed animals,
      which may partly underlie the persistent freezing observed in these animals.
      Together, our data show that heat exposure can induce changes at behavioral,
      physiological, and structural levels, and add to a woefully lacking body of
      literature on fear processes in female animals.

PMID- 24859749
TI  - Microorganisms with claimed probiotic properties: an overview of recent
      literature.
AB  - Probiotics are defined as live microorganisms, which when administered in
      adequate amounts, confer a health benefit on the host. Health benefits have
      mainly been demonstrated for specific probiotic strains of the following genera:
      Lactobacillus, Bifidobacterium, Saccharomyces, Enterococcus, Streptococcus,
      Pediococcus, Leuconostoc, Bacillus, Escherichia coli. The human microbiota is
      getting a lot of attention today and research has already demonstrated that
      alteration of this microbiota may have far-reaching consequences. One of the
      possible routes for correcting dysbiosis is by consuming probiotics. The
      credibility of specific health claims of probiotics and their safety must be
      established through science-based clinical studies. This overview summarizes the
      most commonly used probiotic microorganisms and their demonstrated health claims.
      As probiotic properties have been shown to be strain specific, accurate
      identification of particular strains is also very important. On the other hand,
      it is also demonstrated that the use of various probiotics for immunocompromised
      patients or patients with a leaky gut has also yielded infections, sepsis,
      fungemia, bacteraemia. Although the vast majority of probiotics that are used
      today are generally regarded as safe and beneficial for healthy individuals,
      caution in selecting and monitoring of probiotics for patients is needed and
      complete consideration of risk-benefit ratio before prescribing is recommended. 

PMID- 24859752
TI  - FlyMAD: rapid thermogenetic control of neuronal activity in freely walking
      Drosophila.
AB  - Rapidly and selectively modulating the activity of defined neurons in
      unrestrained animals is a powerful approach in investigating the circuit
      mechanisms that shape behavior. In Drosophila melanogaster, temperature-sensitive
      silencers and activators are widely used to control the activities of genetically
      defined neuronal cell types. A limitation of these thermogenetic approaches,
      however, has been their poor temporal resolution. Here we introduce FlyMAD (the
      fly mind-altering device), which allows thermogenetic silencing or activation
      within seconds or even fractions of a second. Using computer vision, FlyMAD
      targets an infrared laser to freely walking flies. As a proof of principle, we
      demonstrated the rapid silencing and activation of neurons involved in
      locomotion, vision and courtship. The spatial resolution of the focused beam
      enabled preferential targeting of neurons in the brain or ventral nerve cord.
      Moreover, the high temporal resolution of FlyMAD allowed us to discover distinct
      timing relationships for two neuronal cell types previously linked to courtship
      song. 

PMID- 24859753
TI  - Fluorogenic probes for live-cell imaging of the cytoskeleton.
AB  - We introduce far-red, fluorogenic probes that combine minimal cytotoxicity with
      excellent brightness and photostability for fluorescence imaging of actin and
      tubulin in living cells. Applied in stimulated emission depletion (STED)
      microscopy, they reveal the ninefold symmetry of the centrosome and the spatial
      organization of actin in the axon of cultured rat neurons with a resolution
      unprecedented for imaging cytoskeletal structures in living cells.

PMID- 24859754
TI  - miR-142 orchestrates a network of actin cytoskeleton regulators during
      megakaryopoiesis.
AB  - Genome-encoded microRNAs (miRNAs) provide a posttranscriptional regulatory layer
      that controls the differentiation and function of various cellular systems,
      including hematopoietic cells. miR-142 is one of the most prevalently expressed
      miRNAs within the hematopoietic lineage. To address the in vivo functions of miR
      142, we utilized a novel reporter and a loss-of-function mouse allele that we
      have recently generated. In this study, we show that miR-142 is broadly expressed
      in the adult hematopoietic system. Our data further reveal that miR-142 is
      critical for megakaryopoiesis. Genetic ablation of miR-142 caused impaired
      megakaryocyte maturation, inhibition of polyploidization, abnormal proplatelet
      formation, and thrombocytopenia. Finally, we characterized a network of miR-142
      3p targets which collectively control actin filament homeostasis, thereby
      ensuring proper execution of actin-dependent proplatelet formation. Our study
      reveals a pivotal role for miR-142 activity in megakaryocyte maturation and
      function, and demonstrates a critical contribution of a single miRNA in
      orchestrating cytoskeletal dynamics and normal hemostasis.DOI:
      http://dx.doi.org/10.7554/eLife.01964.001. 

PMID- 24859755
TI  - Phosphoprotein SAK1 is a regulator of acclimation to singlet oxygen in
      Chlamydomonas reinhardtii.
AB  - Singlet oxygen is a highly toxic and inevitable byproduct of oxygenic
      photosynthesis. The unicellular green alga Chlamydomonas reinhardtii is capable
      of acclimating specifically to singlet oxygen stress, but the retrograde
      signaling pathway from the chloroplast to the nucleus mediating this response is
      unknown. Here we describe a mutant, singlet oxygen acclimation knocked-out 1
      (sak1), that lacks the acclimation response to singlet oxygen. Analysis of genome
      wide changes in RNA abundance during acclimation to singlet oxygen revealed that
      SAK1 is a key regulator of the gene expression response during acclimation. The
      SAK1 gene encodes an uncharacterized protein with a domain conserved among
      chlorophytes and present in some bZIP transcription factors. The SAK1 protein is
      located in the cytosol, and it is induced and phosphorylated upon exposure to
      singlet oxygen, suggesting that it is a critical intermediate component of the
      retrograde signal transduction pathway leading to singlet oxygen acclimation.DOI:
      http://dx.doi.org/10.7554/eLife.02286.001. 

PMID- 24859757
TI  - Mast cell activation and response to tolterodine in the rat urinary bladder in a
      chronic model of intravesical protamine sulfate and bacterial endotoxin-induced
      cystitis.
AB  - The aim of the present study was to use an animal model of interstitial cystitis
      (IC) in order to investigate the histology and function of the bladder, with a
      particular focus on mast cell degranulation and response to detrusor overactivity
      (DO) to tolterodine. A total of 18 female Sprague-Dawley rats were used. In 12
      rats, lipopolysaccharide (LPS) was intravesically instilled following the
      induction of IC by protamine sulfate (PS) and six rats were subjected to sham
      instillations. Following 1 month, cystometry was performed. The effects of
      tolterodine were tested in half of the animals with IC. All rats in the IC group
      demonstrated DO during the filling phase and no significant changes in the
      frequency or pressure compared with that following tolterodine injection were
      identified. Histological examination revealed a significant increase in the total
      number of infiltrated mast cells in IC rats compared with that in the sham rats
      (P<0.05). Degranulated mast cells were evident in 80% of rats with IC; however,
      they were not apparent in the sham rats. Urinary bladder inflammation, similar to
      that in human IC in terms of degranulated mast cells and bladder function, was
      induced in rats. The animal model used in the present study provided insight into
      the pathophysiological mechanisms underlying the ineffectiveness of
      anticholinergics in patients with overlapping IC and overactive bladder (OAB). 

PMID- 24859756
TI  - Evidence for a DNA-relay mechanism in ParABS-mediated chromosome segregation.
AB  - The widely conserved ParABS system plays a major role in bacterial chromosome
      segregation. How the components of this system work together to generate
      translocation force and directional motion remains uncertain. Here, we combine
      biochemical approaches, quantitative imaging and mathematical modeling to examine
      the mechanism by which ParA drives the translocation of the ParB/parS partition
      complex in Caulobacter crescentus. Our experiments, together with simulations
      grounded on experimentally-determined biochemical and cellular parameters,
      suggest a novel 'DNA-relay' mechanism in which the chromosome plays a mechanical
      function. In this model, DNA-bound ParA-ATP dimers serve as transient tethers
      that harness the elastic dynamics of the chromosome to relay the partition
      complex from one DNA region to another across a ParA-ATP dimer gradient. Since
      ParA-like proteins are implicated in the partitioning of various cytoplasmic
      cargos, the conservation of their DNA-binding activity suggests that the DNA
      relay mechanism may be a general form of intracellular transport in bacteria.DOI:
      http://dx.doi.org/10.7554/eLife.02758.001. 

PMID- 24859759
TI  - Japanese guideline for the oncology FDG-PET/CT data acquisition protocol:
      synopsis of Version 2.0.
AB  - This synopsis outlines the Japanese guideline Version 2.0 for the data
      acquisition protocol of oncology FDG-PET/CT scans that was created by a joint
      task force of the Japanese Society of Nuclear Medicine Technology, the Japanese
      Society of Nuclear Medicine and the Japanese Council of PET Imaging, and was
      published in Kakuigaku-Gijutsu 2013; 33:377-420 in Japanese. The guideline aims
      at standardizing the PET image quality among PET centers and different PET camera
      models by providing criteria for the IEC body phantom image quality as well as
      for the patient PET image quality based on the noise equivalent count (NEC), NEC
      density and liver signal-to-noise ratio, so that the appropriate scanning
      parameters can be determined for each PET camera. This Version 2.0 covers issues
      that were not focused on in Version 1.0, including the accuracy of the
      standardized uptake value (SUV), effect of body size together with adjustment of
      scanning duration, and time-of-flight (TOF) reconstruction technique. Version 2.0
      also presents data acquired with new PET camera models that were not tested in
      Version 1.0. Reference values for physical indicators of phantom image quality
      have been updated as well. 

PMID- 24859758
TI  - Ultrasound in chronic liver disease.
AB  - BACKGROUND: With the high prevalence of diffuse liver disease there is a strong
      clinical need for noninvasive detection and grading of fibrosis and steatosis as
      well as detection of complications. METHODS: B-mode ultrasound supplemented by
      portal system Doppler and contrast-enhanced ultrasound are the principal
      techniques in the assessment of liver parenchyma and portal venous hypertension
      and in hepatocellular carcinoma surveillance. RESULTS: Fibrosis can be detected
      and staged with reasonable accuracy using Transient Elastography and Acoustic
      Radiation Force Imaging. Newer elastography techniques are emerging that are
      undergoing validation and may further improve accuracy. Ultrasound grading of
      hepatic steatosis currently is predominantly qualitative. CONCLUSION: A summary
      of methods including B-mode, Doppler, contrast-enhanced ultrasound and various
      elastography techniques, and their current performance in assessing the liver, is
      provided. TEACHING POINTS: * Diffuse liver disease is becoming more prevalent and
      there is a strong clinical need for noninvasive detection. * Portal hypertension
      can be best diagnosed by demonstrating portosystemic collateral venous flow. * B
      mode US is the principal US technique supplemented by portal system Doppler. * B
      mode US is relied upon in HCC surveillance, and CEUS is useful in the evaluation
      of possible HCC. * Fibrosis can be detected and staged with reasonable accuracy
      using TE and ARFI. * US detection of steatosis is currently reasonably accurate
      but grading of severity is of limited accuracy.

PMID- 24859761
TI  - Generation and characterization of nanobodies against rhGH expressed as sfGFP
      fusion protein.
AB  - Growth hormone (GH) deficiencies are diagnosed in most children with short
      stature and treated with a long course of administrating expensive and daily
      doses of recombinant human GH (rhGH or Somatropin(r)). This work describes for
      the first time the production of several GH specific nanobodies with great
      potential in the field of GH production and detection. Nanobodies are the
      smallest intact antigen binders derived from heavy chain-only antibodies (HCAbs)
      of camelids. They are very stable, highly soluble and are produced as recombinant
      proteins in Escherichiacoli at an affordable cost for various biotechnological
      applications. To increase its solubility and immunogenicity, GH was produced as
      fusion with superfolder green fluorescent protein (sfGFP) and was used in this
      form to successfully immunize an adult camel. The active involvement of HCAbs in
      the specific camel immune response encouraged the preparation of large nanobody
      "immune" library. Phage display biopanning of this library against GH resulted in
      the isolation of five interesting and different nanobodies, referred to as
      NbGH01, 02, 03, 04 and 06. All nanobodies were able to recognize GH in its fusion
      and free formats and the detection sensitivity ranged from 0.5 to 10 ng/ml in
      sandwich ELISA. Pure rhGH was successfully purified by affinity chromatography,
      using immobilized NbGH06, from the cleavage reaction of fusion proteins with the
      tobaccos etch virus (TEV) protease. These specific molecular binders, especially
      NbGH06, provide valuable tools for rhGH diagnostic as well as for production
      purposes.

PMID- 24859760
TI  - Abnormal n-6 fatty acid metabolism in cystic fibrosis is caused by activation of
      AMP-activated protein kinase.
AB  - Cystic fibrosis (CF) patients and model systems exhibit consistent abnormalities
      in PUFA metabolism, including increased metabolism of linoleate to arachidonate.
      Recent studies have connected these abnormalities to increased expression and
      activity of the Delta6- and Delta5-desaturase enzymes. However, the mechanism
      connecting these changes to the CF transmembrane conductance regulator (CFTR)
      mutations responsible for CF is unknown. This study tests the hypothesis that
      increased activity of AMP-activated protein kinase (AMPK), previously described
      in CF bronchial epithelial cells, causes these changes in fatty acid metabolism
      by driving desaturase expression. Using CF bronchial epithelial cell culture
      models, we confirm elevated activity of AMPK in CF cells and show that it is due
      to increased phosphorylation of AMPK by Ca(2+)/calmodulin-dependent protein
      kinase kinase beta (CaMKKbeta). We also show that inhibition of AMPK or CaMKKbeta
      reduces desaturase expression and reverses the metabolic alterations seen in CF
      cells. These results signify a novel AMPK-dependent mechanism linking the genetic
      defect in CF to alterations in PUFA metabolism.

PMID- 24859762
TI  - Aromatic diacylhydrazine derivatives as a new class of polo-like kinase 1 (PLK1)
      inhibitors.
AB  - A novel class of aromatic diacylhydrazine derivatives was designed as PLK1
      inhibitors. All the 19 new synthesized compounds were assayed for antitumor
      activity against the respective cervical cancer cells. In which, nine compounds
      with better antitumor activities were further tested for their PLK1 inhibitory
      activity. Last, we have successfully found that compound 7k showed both the
      promising antitumor activity with IC50 of 0.17 MUM against the cervical cancer
      cells, and also processed the most potent PLK1 inhibitory activity with IC50 of
      0.03 MUM. In addition, docking simulation also carried out in this study to give
      a potent prediction binding mode between the small molecule and PKL1 (PDB code:
      1umw) protein. 

PMID- 24859763
TI  - Molecular and cytotoxic properties of hIAPP17-29 and rIAPP17-29 fragments: a
      comparative study with the respective full-length parent polypeptides.
AB  - The human islet polypeptide (hIAPP) or amylin is a 37-residue peptide hormone
      secreted by beta-cells of the islet of Langerhans in the pancreas. Unlike the rat
      variant of IAPP (rIAPP), human amylin is highly amyloidogenic and is found as
      amyloid deposits in nearly 95% of patients afflicted with type 2 diabetes
      mellitus (T2DM). Human and rat IAPP have nearly identical primary sequence
      differing at only six positions which are encompassed within the 17-29 aminoacid
      region. Using Circular Dichroism (CD), Dynamic Light Scattering (DLS) and ThT
      fluorescence (Th-T), we examined the aggregation properties of both full-length
      hIAPP1-37 and the related peptide fragment hIAPP17-29. For the sake of
      comparison, similar experiments were carried out on the respective rat variants
      rIAPP1-37 and rIAPP17-29. These studies were conducted at physiological pH in
      buffered solution not containing fluorinated co-solvents as well as in the
      presence of model membranes (LUV). In addition, the cytotoxic activity of the
      investigated peptides was determined toward different pancreatic beta-cell lines.
      All the peptide studied in this work resulted cytotoxic despite beta-sheet
      structure being observed, in vitro, for the hIAPP1-37 only. This suggests that
      beta-sheet conformational transition that generally precedes the fibril
      formation, is not a prerequisite for toxicity towards beta-cells. Interestingly,
      confocal microscopy indicated that the IAPP peptides can enter the cell and might
      exert their toxic action at an intracellular level. 

PMID- 24859764
TI  - Synthesis and identification of chiral aminomethylpiperidine carboxamides as
      inhibitor of collagen induced platelet activation.
AB  - A series of chiral lactam carboxamides of aminomethylpiperidine were synthesized
      and investigated for the collagen induced in vitro anti-platelet efficacy and
      collagen plus epinephrine induced in vivo pulmonary thromboembolism. The compound
      31a (30 MUM/kg) displayed a remarkable antithrombotic efficacy (60% protection)
      which was sustained for more than 24 h and points to its excellent
      bioavailability. The compounds 31a (IC50 = 6.6 MUM) and 32a (IC50 = 37 MUM), as
      well as their racemic mixture 28i (IC50 = 16 MUM) significantly inhibited
      collagen-induced human platelet aggregation in vitro. Compound 34c displayed dual
      mechanism of action against both collagen (IC50 = 3.3 MUM) and U46619 (IC50 = 2.7
      MUM) induced platelet aggregation. The pharmacokinetic study of 31a indicated
      very faster absorption, prolonged and constant systemic exposure and thereby
      exhibiting better therapeutic response. 

PMID- 24859765
TI  - Epigenetic repression of HOXB cluster in oral cancer cell lines.
AB  - OBJECTIVE: Aberrant DNA methylation is a fundamental transcriptional control
      mechanism in carcinogenesis. The expression of homeobox genes is usually
      controlled by an epigenetic mechanism, such as the methylation of CpG islands in
      the promoter region. The aim of this study was to describe the differential
      methylation pattern of HOX genes in oral squamous cell carcinoma (OSCC) cell
      lines and transcript status in a group of hypermethylated and hypomethylated
      genes. DESIGN: Quantitative analysis of DNA methylation was performed on two OSCC
      cell lines (SCC4 and SCC9) using a method denominated Human Homeobox Genes
      EpiTect Methyl qPCR Arrays, which allowed fast, precise methylation detection of
      24 HOX specific genes without bisulfite conversion. RESULTS: Methylation greater
      than 50% was detected in HOXA11, HOXA6, HOXA7, HOXA9, HOXB1, HOXB2, HOXB3, HOXB4,
      HOXB5, HOXB6, HOXC8 and HOXD10. Both cell lines demonstrated similar
      hypermethylation status for eight HOX genes. A similar pattern of promoter
      hypermethylation and hypomethylation was demonstrated for the HOXB cluster and
      HOXA cluster, respectively. Moreover, the hypermethylation profile of the HOXB
      cluster, especially HOXB4, was correlated with decreased transcript expression,
      which was restored following treatment with 5-aza-2'-deoxycytidine. CONCLUSIONS:
      The homeobox methylation profile in OSCC cell lines is consistent with an
      epigenetic biomarker.

PMID- 24859766
TI  - Important aspects regarding the role of microorganisms in bisphosphonate-related
      osteonecrosis of the jaws.
AB  - Bisphosphonate-related osteonecrosis of the jaws (BRONJ) is an important side
      effect of bisphosphonates, whose etiopathogenesis has not been completely
      elucidated. Theories pointing to bone turnover and angiogenesis inhibition, as
      well as effects on epithelial cells of oral mucosa and the role of microorganisms
      have been reported. Nevertheless, the true contribution of each one of these
      factors to BRONJ is unknown. We present here a literature review focusing on
      important aspects regarding the role of microorganisms in BRONJ development.
      Knowledge about specific microbiota and its role in the etiopathogenesis of this
      disease can help the optimisation of preventive and therapeutic interventions in
      patients with or at-risk for BRONJ. 

PMID- 24859767
TI  - Plasma polyunsaturated fatty acids and periodontal recovery in Taiwanese with
      periodontitis: a significant relationship.
AB  - BACKGROUND: Plasma levels of polyunsaturated fatty acids (PUFAs) are different
      before and after periodontal treatment. Asians and Westerners have significantly
      different baseline levels of plasma PUFAs. However, no Asian study has reported
      the effects of nonsurgical treatment on the correlation between periodontal
      condition and plasma levels of PUFAs. We analyzed whether recovery from
      periodontitis was correlated with the elevation of plasma fatty acids 3 months
      after the nonsurgical intervention and with no recommended supplements. DESIGN:
      Thirty-five Taiwanese patients with periodontitis were recruited. Probing pocket
      depths (PPDs) and clinical attachment levels (CALs) were measured at baseline and
      3 months after the nonsurgical treatment. Plasma levels of fatty acids were
      determined using gas chromatography. Differences and correlations between plasma
      fatty acid composition and periodontitis severity at baseline and 3 months after
      treatment were determined. RESULTS: Twenty-six patients completed the study. At
      the baseline, PPDs were negatively correlated with plasma n-3 PUFAs (r=-0.52,
      p<0.01), but at 3 months post intervention, periodontitis severity had declined
      and the weight percentages of n-3 PUFAs, DPA, and DHA were significantly
      (p=0.019, 0.005, and 0.037, respectively) higher. The recovery percentages of
      CALs were positively and significantly correlated with plasma DeltaPUFAs and the
      percentage of Deltan-3 PUFAs in DeltaPUFAs (r=0.42 and 0.45, respectively; p<0.05
      for both). CONCLUSIONS: We conclude that a higher weight percentage of n-3 PUFAs
      in total PUFAs was related to the recovery of CALs 3 months after the nonsurgical
      periodontal treatment. However, no such relationship was found for PPDs.

PMID- 24859768
TI  - Prevalence and quantification of the uncommon Archaea phylotype Thermoplasmata in
      chronic periodontitis.
AB  - OBJECTIVE: Chronic periodontitis is a chronic inflammatory disease of the
      periodontal tissues and is caused by invasion of certain types of bacteria and
      Archaea, with Methanobrevibacter oralis as the predominant archaeon. In this
      study, we investigated the prevalence and quantity of the newly discovered
      Archaea phylotype Thermoplasmata in patients with chronic periodontitis. METHODS:
      Subgingival plaque samples were obtained from 49 patients with chronic
      periodontitis and 45 periodontally healthy subjects. Qualitative analyses of
      Archaea and class Thermoplasmata were carried out by amplification of 16S rRNA
      genes in DNA extracts from plaque samples, and all the samples were
      quantitatively analyzed by real-time polymerase chain reaction (PCR). RESULTS:
      The prevalence of Archaea in patients with chronic periodontitis was 69.4%
      according to the conventional PCR results, but was 87.8% according to real-time
      PCR. In the control group, three samples were detected as positive, but none of
      these were confirmed in qualitative analyses. The prevalence of class
      Thermoplasmata was 18.4% by nested PCR and 24.5% by quantitative PCR in the
      chronic periodontitis group. The prevalence of Thermoplasmata was significantly
      lower than that of total Archaea. The relative abundances of Archaea and
      Thermoplasmata varied among samples. Thermoplasmata were not the predominant
      archaeons in the subgingival dental plaque. Among the clinical parameters of
      patients with periodontitis, probing depth was positively associated with Archaea
      detection. CONCLUSIONS: The existence of Archaea was correlated closely with the
      presence of chronic periodontitis. Thermoplasmata represented a minor archaeon in
      periodontal infection.

PMID- 24859769
TI  - Modified schirmer test--a screening tool for xerostomia among subjects on
      antidepressants.
AB  - OBJECTIVE: The aim of the present study is to assess salivary flow rate in the
      subjects who were on antidepressant medications and its comparison with healthy
      controls and assessment of unstimulated salivary flow rate by modified Schirmer
      test (MST) and volumetric method (spitting method) for evaluation of xerostomia
      and whether any correlation exists between two methods. MATERIAL AND METHODS:
      Thirty subjects who were on antidepressants were divided into two groups:
      tricyclic antidepressants (TCA) and selective sertonin reuptake inhibitors (SSRI)
      of 15 each, compared with 30 age and gender matched controls. Unstimulated
      salivary flow rate was measured by both MST and spitting method. RESULTS: The
      unstimulated salivary flow rate measured by MST at the end of 3rd minute was 13.7
      +/- 10.08, 19.86 +/- 8.95 and 31.0 +/- 5.4 mm and by spitting method was 0.12 +/-
      0.07, 0.19 +/- 0.10 and 0.30 +/- 0.75 ml/min in TCA, SSRI and controls
      respectively (p<0.001). The Pearson correlation coefficient of r=0.85 shows
      excellent correlation between the two screening tests. Sensitivity and
      Specificity of MST was 90.9% and 31.5%. CONCLUSION: Salivary flow rate was less
      in antidepressant subjects when compared to the healthy controls. Results of the
      present study showed an excellent correlation excellent correlation between the
      two screening tests which suggests that MST can be routinely used as chair-side
      screening tool to evaluate hyposalivation which is time saving, patient friendly
      and specific of salivary secretions.

PMID- 24859771
TI  - Opportunities for image analysis in radiation oncology.

PMID- 24859770
TI  - Inhibitory effects of ameloblastin on epithelial cell proliferation.
AB  - OBJECTIVE: Ameloblastin is an enamel matrix protein expressed in several tissues.
      Many potential mechanisms have been identified by which ameloblastin functions as
      an extracellular matrix protein. However, the biological effects of ameloblastin
      on gingival epithelial cells remain unclear. In the present study, we established
      a novel system to purify recombinant human ameloblastin and clarified its
      biological functions in epithelial cells in vitro. DESIGN: Recombinant human
      ameloblastin was isolated from COS-7 cells overexpressing HaloTag-fused human
      ameloblastin by the HaloTag system and then purified further by reverse-phase
      high-performance liquid chromatography. SCC-25 cells, derived from human oral
      squamous cell carcinoma, were treated with recombinant ameloblastin and then cell
      survival was assessed by a WST-1 assay. Cell cycle analysis was performed by flow
      cytometry. RESULTS: The novel purification system allowed effective recovery of
      the recombinant ameloblastin proteins at a high purity. Recombinant ameloblastin
      protein was found to suppress the proliferation of SCC-25 cells. Flow cytometric
      analysis showed that ameloblastin treatment induced cell cycle arrest G1 phase.
      CONCLUSIONS: We developed a procedure for production of highly purified
      recombinant human ameloblastin. Biological analyses suggest that ameloblastin
      induces cell cycle arrest in epithelial cells and regulates the progression of
      periodontitis.

PMID- 24859772
TI  - Involvement of histone H3 phosphorylation via the activation of p38 MAPK pathway
      and intracellular redox status in cytotoxicity of HL-60 cells induced by Vitex
      agnus-castus fruit extract.
AB  - We have demonstrated that an extract from the ripe fruit of Vitex angus-castus
      (Vitex), might be a promising anticancer candidate. In order to further provide a
      molecular rationale for clinical development in anticancer therapy, a detailed
      mechanism underlying the efficacy of Vitex against HL-60 cells was investigated.
      Vitex induced a dose- and time-dependent decrease in cell viability associated
      with induction of apoptosis and G(2)/M cell cycle arrest, both of which were
      suppressed by the addition of SB203580, an inhibitor for p38 MAPK. Furthermore,
      SB203580 significantly suppressed Vitex-induced phosphorylation of histone H3, a
      downstream molecule of p38 MAPK known to be involved in apoptosis induction in
      tumor cells. Notably, Vitex induced upregulation of intracellular ATP, known to
      bind its binding pocket inside activated p38 MAPK and to be required for the
      activation of p38 MAPK pathway. These results, thus, suggest that upregulation of
      intracellular ATP and phosphorylation of histone H3 are closely associated with
      the activation of p38 MAPK pathway, consequently contributing to Vitex-mediated
      cytotoxicity. Intriguingly, a significant decrease of intracellular ROS levels
      and downregulation of expression level of gp91(phox), an important component of
      NADPH oxidase, were observed in Vitex-treated cells. A greater decline in ROS
      levels along with enhanced apoptosis was observed after treatment with Vitex in
      combination with SnPP, an inhibitor specific for HO-1. Since NADPH oxidase and HO
      1 are closely correlated to redox status associated with intracellular ROS
      levels, the two enzymes are suggested to be implicated in Vitex-mediated
      cytotoxicity in HL-60 cells by regulating ROS generation. We also suggest that
      activation of the p38 MAPK pathway may be dependent on the alterations of
      intracellular ATP levels, rather than that of intracellular ROS levels. These
      results may have important implications for appropriate clinical uses of Vitex
      and provide novel insights into the interaction between Vitex and other
      conventional drugs capable of affecting intracellular redox status.

PMID- 24859773
TI  - Effect of cofactor folate on the growth of Corynebacterium glutamicum SYPS-062
      and L-serine accumulation.
AB  - The direct fermentative production of L-serine from sugar has attracted
      increasing attention. Corynebacterium glutamicum SYPS-062 can directly convert
      sugar to L-serine. In this study, the effects of exogenous and endogenous
      regulation of cofactor folate on C. glutamicum SYPS-062 growth and L-serine
      accumulation were investigated. For exogenous regulation, the inhibitor
      (sulfamethoxazole) or precursor (p-aminobenzoate) of folate biosynthesis was
      added to the medium, respectively. For endogenous regulation, the gene (pabAB)
      that encodes the key enzyme of folate biosynthesis was knocked out or
      overexpressed to obtain the recombinant C. glutamicum SYPS-062 DeltapabAB and
      SYPS-062(pJC-tac-pabAB), respectively. The results indicated that decreased
      levels of cofactor folate supported L-serine accumulation, whereas increased
      levels of cofactor folate aided in cell growth of C. glutamicum SYPS-062. Thus,
      this study not only elucidated the role of folate in C. glutamicum SYPS-062
      growth and L-serine accumulation, but also provided a novel and convenient
      approach to regulate folate biosynthesis in C. glutamicum. 

PMID- 24859774
TI  - Trace element concentrations in eggshells and egg contents of black-tailed gull
      (Larus crassirostris) from Korea.
AB  - Concentrations of trace elements (cadmium, lead, copper, manganese and zinc) were
      examined in eggs of black-tailed gulls (Larus crassirostris) from Hongdo Island,
      Korea to determine the difference and distribution of trace elements in eggshells
      and egg contents. Cadmium, lead and manganese concentrations were greater in
      eggshells than in egg contents. In contrast, zinc concentrations were higher in
      egg contents than in eggshells. Trace element concentrations followed the order:
      zinc > lead = manganese = copper > cadmium (eggshells) and zinc > copper >
      manganese > lead > cadmium (egg contents). Cadmium concentrations were relatively
      low (<1 MUg/g dw) in egg contents and eggshells. Concentrations of cadmium, lead
      and copper were significantly correlated between egg contents and eggshells. This
      indicates that cadmium, lead and copper levels in the eggshell can reflect their
      levels in the egg contents. There was also a high ratio (3.2) of eggshell/egg
      content for lead. These results indicate that the eggshell might be useful as a
      bio-indicator for monitoring cadmium, lead and copper in the egg content.

PMID- 24859775
TI  - Laparoendoscopic partial nephrectomy in single-incision triangulated umbilical
      surgery (SITUS) technique: early experience.
AB  - BACKGROUND: Nephron sparing surgery for renal tumors has evolved as the standard
      of care for resectable renal tumors. Laparoscopic partial nephrectomy (PN) has
      gained recognition after technical refinements were able to match the well
      established criteria for open partial nephrectomy. Laparoendoscopic surgery
      (LESS) is one of the approaches to further minimize invasiveness of laparoscopic
      surgery. OBJECTIVE: We report our initial experience with LESS partial
      nephrectomy in single-incision transumbilical surgery technique (SITUS) in daily
      clinical practice. DESIGN, SETTING, AND PARTICIPANTS: From 2010, patients
      undergoing SITUS-PN were prospectively evaluated. Patients with small, solitary
      or multiple, exophytic-enhancing renal masses were selected, whereas patients
      with solitary kidney, endophytic or hilar tumors were excluded. Important
      clinical data, PADUA and RENAL score, were assessed prospectively. MEASUREMENTS:
      Patients' characteristics, perioperative, hematologic and pathologic data as well
      as pain evaluation using the visual analogue pain scale (VAPS) were assessed.
      RESULTS AND LIMITATIONS: A total of 13 patients underwent LESS-PN/SITUS-PN (6
      right and 7 left renal units). One patient was converted to conventional
      laparoscopy requiring two additional ports to treat bleeding from renal vessels.
      Pathology revealed renal cell carcinoma in nine patients, oncocytoma in one and
      benign cyst in three patients. No positive surgical margin was observed. The mean
      blood loss was 2.1 g/dl [range 0.5-4.5 g/dl] in hemoglobin. Minimal discomfort
      was noted at discharge (VAPS = 0.2 +/- 0.6 [range 0-2]/10]. CONCLUSION: LESS
      partial nephrectomy in SITUS technique is feasible for selected exophytic tumors
      and has been integrated into our armamentarium for nephron sparing minimally
      invasive surgical treatment.

PMID- 24859776
TI  - Update on the use of diode laser in the management of benign prostate obstruction
      in 2014.
AB  - AIM: To determine the status quo in respect of various diode lasers and present
      the techniques in use, their results and complications. We assess how these
      compare with transurethral resection of the prostate and other types of laser in
      randomized controlled trials (RCTs). When adequate RCTs were not available, case
      studies and reports were evaluated. MATERIALS AND METHODS: Laser for the
      treatment of benign prostatic hyperplasia (BPH) has aroused the interest and
      curiosity of urologists as well as patients. The patient associates the term
      laser with a successful and modern procedure. The journey that started with
      coagulative necrosis of prostatic adenoma based on neodymium: yttrium-aluminum
      garnet (Nd:YAG) laser has culminated in endoscopic "enucleation" with holmium
      laser. Diode laser is being used in urology for about 10 years now. Various
      techniques have been employed to relieve bladder outlet obstruction due to BPH.
      RESULTS: The diode laser scenario is marked by a diversity of surgical techniques
      and wavelengths. We summarize the current published literature in respect of
      functional results and complications. CONCLUSION: More randomized controlled
      studies are needed to determine the position and the ideal technique of diode
      laser treatment for BPH.

PMID- 24859777
TI  - Membrane hyperpolarization induced by endoplasmic reticulum stress facilitates
      ca(2+) influx to regulate cell cycle progression in brain capillary endothelial
      cells.
AB  - Upregulation of the Kir2.1 channel during endoplasmic reticulum (ER) stress in t
      BBEC117, an immortalized bovine brain endothelial cell line, caused a sustained
      increase in intracellular Ca(2+) concentration ([Ca(2+)]i) and a facilitation of
      cell death. Expressions of Ca(2+) influx channels (TRPC, Orai1, STIM1) were
      unchanged by ER stress. The ER stress-induced [Ca(2+)]i increase was mainly
      attributed to the deeper resting membrane potential due to Kir2.1 upregulation.
      ER stress arrested at the G2/M phase and it was attenuated by an inhibitor of
      Kir2.1. These results indicate that Kir2.1 upregulation by ER stress facilitates
      cell death via regulation of cell cycle progression in t-BBEC117. 

PMID- 24859778
TI  - Skeletal muscle is an endocrine organ.
AB  - Skeletal muscle plays a key role in postural retention as well as locomotion for
      maintaining the physical activities of human life. Skeletal muscle has a second
      role as an elaborate energy production and consumption system that influences the
      whole body's energy metabolism. Skeletal muscle is a specific organ that
      engenders a physical force, and exercise training has been known to bring about
      multiple benefits for human health maintenance and/or improvement. The mechanisms
      underlying the improvement of the human physical condition have been revealed:
      skeletal muscle synthesizes and secretes multiple factors, and these muscle
      derived factors, so-called as myokines, exert beneficial effects on peripheral
      and remote organs. In this short review, we focus on the third aspect of skeletal
      muscle function - namely, the release of multiple types of myokines, which
      constitute a broad network for regulating the function of remote organs as well
      as skeletal muscle itself. We conclusively show that skeletal muscle is one of
      the endocrine organs and that understanding the mechanisms of production and
      secretion of myokines may lead to a new pharmacological approach for treatment of
      clinical disorders. 

PMID- 24859779
TI  - Yellow wine polyphenolic compounds inhibit matrix metalloproteinase-2, -9
      expression and improve atherosclerotic plaque in LDL-receptor-knockout mice.
AB  - Many epidemiological studies have strongly suggested an inverse correlation
      between dietary polyphenol consumption and reduced risks of cardiovascular
      diseases. Yellow rice wine is a Chinese specialty and one of the three most
      ancient wines in the world (Shaoxing rice wine, beer, and grape wine). There is a
      large amount of polyphenol substances in yellow rice wine. This experiment was
      designed to study the potential beneficial effects of yellow wine polyphenolic
      compounds (YWPC) from yellow rice wine on progression of atherosclerosis in vivo
      and to further explore its underlying mechanisms. Six-week-old male LDL-receptor
      knockout mice were treated with high-fat diet to establish the mouse model with
      atherosclerosis. Animals received 10, 30, or 50 mg/kg per day of YWPC or 10 mg/kg
      per day rosuvastatin or water (vehicle) for 14 weeks. The results indicated that
      YWPC and rosuvastatin significantly decreased circulating total cholesterol and
      low-density lipoprotein cholesterol. Compared to the control group, the
      atherosclerosis lesion area in the rosuvastatin-intervention group and YWPC at
      doses of 10, 30, and 50 mg/kg per day intervention groups decreased by 74.14%,
      18.51%, 40.09%, and 38.42%, respectively. YWPC and rosuvastatin decreased the
      expression and activity of matrix metalloproteinases (MMP)-2, 9, whereas the
      expression of the endogenous inhibitors of these proteins, namely, tissue
      inhibitors of matrix metalloproteinases (TIMP)-1, 2, increased when compared to
      the control group. It can be concluded that the YWPC is similar to the benefic
      effects of rosuvastatin on cardiovascular system. These effects may be attributed
      to their anti-atherosclerotic actions by lowering lipid and modulating the
      activity and expression of MMP-2, 9 and TIMP-1, 2. 

PMID- 24859780
TI  - Soluble guanylate cyclase redox state under hypoxia or hypoxia/reoxygenation in
      isolated monkey coronary arteries.
AB  - Hypoxia or hypoxia/reoxygenation impairs nitric oxide (NO)-mediated relaxation
      through the increase in superoxide generation in monkey coronary arteries.
      Soluble guanylate cyclase (sGC), the target enzyme of NO, has been shown to
      change from the NO-sensitive reduced form to the NO-insensitive oxidized/heme
      free form under substantial oxidative stress, so the present study investigated
      whether hypoxia or hypoxia/reoxygenation influences sGC redox equilibrium. In
      isolated monkey coronary arteries without endothelium, the relaxation caused by
      the sGC stimulator BAY 41-2272 (Emax: 93.3% +/- 2.2%) was somewhat impaired under
      hypoxia (Emax: 86.3% +/- 2.6%) or hypoxia/reoxygenation (Emax: 86.1% +/- 3.2%),
      whereas that by the sGC activator BAY 60-2770 (Emax: 86.0% +/- 3.2%) was
      significantly augmented under hypoxia (Emax: 94.4% +/- 1.3%) or
      hypoxia/reoxygenation (Emax: 95.5% +/- 1.1%). In addition, cGMP formation in
      response to BAY 41-2272 and BAY 60-2770 was inhibited and stimulated,
      respectively, under hypoxia or hypoxia/reoxygenation. The effects of hypoxia or
      hypoxia/reoxygenation on BAY 41-2272- and BAY 60-2770-induced vasorelaxation were
      completely canceled by the treatment with the superoxide dismutase mimetic
      tempol. These findings suggest that sGC redox equilibrium in the coronary artery
      is shifted towards the NO-insensitive form under hypoxia or hypoxia/reoxygenation
      and that superoxide seems to play an important role in this shift. 

PMID- 24859782
TI  - Mycobacterium tuberculosis lipoarabinomannan antibodies are associated to
      rheumatoid arthritis in Sardinian patients.
AB  - Little is known regarding the environmental factors at play in igniting
      rheumatoid arthritis (RA) autoimmunity, although an association between
      Mycobacteria and RA has been documented. This pilot study focused on examining a
      possible involvement of Mycobacterium tuberculosis (MTB) and Mycobacterium avium
      ss. paratuberculosis (MAP) in RA. We measured out the serum levels of IgG
      antibody against different mycobacterial antigens in Sardinian patients and
      controls, by an enzyme-linked immunosorbent assay. The population study was
      composed of 61 RA patients under different therapies and 52 healthy controls,
      whereas the antigens tested were MTB lipoarabinomannan (ManLAM), MAP heath shock
      protein 70, and MAP protein tyrosine phosphatase. The frequencies of anti-ManLAM
      antibodies were higher in the RA group (23 %) compared to the healthy controls
      (5.7 %) (AUC = 0.7; p < 0.0001), whereas serum reactivity to MAP antigens was not
      observed. ManLAM antigen was also detected in the plasma of three RA patients
      (which were anti-ManLAM antibody positive) by Western blot analysis using anti
      Man-LAM monoclonal antibodies. The data produced corroborate the hypothesis of a
      potential association between MTB ManLAM and RA disease, but so far, further
      studies are necessary to understand its role in RA pathogenesis.

PMID- 24859781
TI  - Depression, anxiety, and quality of life in a large cohort of patients with
      rheumatic diseases: common, yet undertreated.
AB  - A growing amount of literature has explored mainly the role of depression (and/or
      anxiety) in patients with rheumatic disorders. We aimed at determining the
      prevalence of depression, anxiety, and their association with quality of life
      among patients attending a rheumatology clinic, focusing on data regarding
      concomitant psychiatric treatment. Depression, anxiety, and quality of life were
      assessed using the Zung Self-Rating Depression Scale, the Hamilton Anxiety Scale,
      and the Health Assessment Questionnaire, respectively. Overall, 514 rheumatologic
      patients were studied. Depression and anxiety were documented in 21.8 and 30.8 %
      of the population, respectively, and correlated significantly with quality of
      life. Only 13.4 % of patients with depressive symptoms and 12.1 % of patients
      with anxiety symptoms were receiving antidepressant or antianxiety medication.
      Given the wide therapeutic armamentarium available nowadays for the management of
      depression and anxiety, an increased awareness among physicians dealing with
      rheumatologic patients is warranted in order to integrate detection and effective
      treatment of anxiety and depression into the routine clinical practice. Special
      attention should be paid to female patients, patients with longer disease
      duration, and/or those with established disability.

PMID- 24859783
TI  - Risk of coronary artery disease in patients with systemic sclerosis: a systematic
      review and meta-analysis.
AB  - Several chronic inflammatory disorders, such as rheumatoid arthritis and systemic
      lupus erythematosus, have been shown to increase coronary artery disease (CAD)
      risk but the data on systemic sclerosis (SSc) is unclear. We conducted a
      systematic review and meta-analysis of observational studies that reported odds
      ratio, relative risk, hazard ratio, or standardized incidence ratio comparing CAD
      risk in patients with SSc versus non-SSc participants. Pooled risk ratio and 95 %
      confidence intervals were calculated using a random effect, generic inverse
      variance method. Four studies were identified and included in our data analysis.
      The pooled risk ratio of CAD in patients with SSc was 1.82 (95 % CI, 1.40 to
      2.36). The statistical heterogeneity of this meta-analysis was moderate with an I
      (2) of 73 %. Our study demonstrated a statistically significant increased CAD
      risk among patients with SSc. 

PMID- 24859786
TI  - Serum alpha tocopherol, vitamin B12, and folate levels in childhood acute
      lymphoblastic leukemia survivors with and without neuropathy.
AB  - Various micronutrients are essential for optimal functioning of the peripheral
      nervous system. Serum vitamin E, vitamin B12, and folic acid were estimated in
      childhood acute lymphoblastic leukemia survivors aged between 5 and 18 years in
      first continuous remission within 3 years of completion of vincristine-based
      chemotherapy with and without electrophysiologically defined neuropathy. A total
      of 80 children were studied. Neuropathy was seen in 27 (33.75%) children
      electrophysiologically. None of the children had vitamin E deficiency. However,
      the alpha tocopherol/(cholesterol + triglyceride) ratio was significantly lower
      in children with neuropathy (P = .05). The prevalence of folate (P = .48) and
      vitamin B12 (P = .21) deficiency in children with and without neuropathy was not
      significantly different. Thus, the prevalence of deficiencies of these
      micronutrients was not significantly different in childhood acute lymphoblastic
      leukemia survivors with or without electrophysiologically defined neuropathy. 

PMID- 24859784
TI  - Genetic architecture of lipid traits changes over time and differs by race:
      Princeton Lipid Follow-up Study.
AB  - Dyslipidemia is a major risk factor for CVD. Previous studies on lipid
      heritability have largely focused on white populations assessed after the obesity
      epidemic. Given secular trends and racial differences in lipid levels, this study
      explored whether lipid heritability is consistent across time and between races.
      African American and white nuclear families had fasting lipids measured in the
      1970s and 22-30 years later. Heritability was estimated, and bivariate analyses
      between visits were conducted by race using variance components analysis. A total
      of 1,454 individuals (age 14.1/40.6 for offspring/parents at baseline; 39.6/66.5
      at follow-up) in 373 families (286 white, 87 African American) were included.
      Lipid trait heritabilities were typically stronger during the 1970s than the
      2000s. At baseline, additive genetic variation for LDL was significantly lower in
      African Americans than whites (P = 0.015). Shared genetic contribution to lipid
      variability over time was significant in both whites (all P < 0.0001) and African
      Americans (P <= 0.05 for total, LDL, and HDL cholesterol). African American
      families demonstrated shared environmental contributions to lipid variation over
      time (all P <= 0.05). Lower heritability, lower LDL genetic variance, and durable
      environmental effects across the obesity epidemic in African American families
      suggest race-specific approaches are needed to clarify the genetic etiology of
      lipids.

PMID- 24859787
TI  - Prader-Willi syndrome with a long-contiguous stretch of homozygosity not covering
      the critical region.
AB  - Prader-Willi syndrome is a common and complex disorder affecting multiple
      systems. Its main manifestations are infantile hypotonia with a poor sucking
      reflex, a characteristic facial appearance, mild mental retardation, hypogonadism
      and early-onset obesity. Prader-Willi syndrome is due to the absence of
      paternally expressed imprinted genes at 15q11.2-13, and 3 main mechanisms are
      known to be involved in its pathogenesis: paternal microdeletions, maternal
      uniparental disomy events, and imprinting defects. DNA methylation analysis can
      detect almost all individuals with Prader-Willi syndrome but is unable to
      distinguish between the molecular classes of the disease. Thus, additional
      methods are necessary to identify the molecular classes. Here, we employed
      chromosomal microarray analysis-single nucleotide polymorphism for diagnosis and
      detected a long-contiguous stretch of homozygosity on chromosome 15, which is
      highly predictive of maternal uniparental disomy on chromosome 15. Other methods,
      including fluorescence in situ hybridization, chromosomal microarray analysis
      comparative genomic hybridization, genotyping and family linkage analysis, were
      performed for further validation. In conclusion, our study highlights the use of
      long-contiguous stretch of homozygosity detection for the diagnosis of Prader
      Willi syndrome. 

PMID- 24859788
TI  - Dietary and medication adjustments to improve seizure control in patients treated
      with the ketogenic diet.
AB  - Unlike anticonvulsant drugs and vagus nerve stimulation, there are no guidelines
      regarding adjustments to ketogenic diet regimens to improve seizure efficacy once
      the diet has been started. A retrospective chart review was performed of 200
      consecutive patients treated with the ketogenic diet at Johns Hopkins Hospital
      from 2007 to 2013. Ten dietary and supplement changes were identified, along with
      anticonvulsant adjustments. A total of 391 distinct interventions occurred, of
      which 265 were made specifically to improve seizure control. Adjustments led to
      >50% further seizure reduction in 18%, but only 3% became seizure-free. The
      benefits of interventions did not decrease over time. There was a trend towards
      medication adjustments being more successful than dietary modifications (24% vs
      15%, P = .08). No single dietary change stood out as the most effective, but
      calorie changes were largely unhelpful (10% with additional benefit). 

PMID- 24859789
TI  - Advance directive repository.
AB  - As the population ages, end-of-life care (EOLC) becomes an increasingly pressing
      issue. Advance directives (ADs) are legal documents that allow individuals to
      convey their decisions about EOLC. Although ADs have been shown to reduce EOLC
      costs, most people do not have ADs. To address this issue, we recently proposed
      that Congress instruct the Centers for Medicare and Medicaid Services (CMS) to
      collect ADs from Medicare beneficiaries. Herein, we outline how to implement this
      solution. 

PMID- 24859790
TI  - Early and frequent development of ocular hypertension in children with nephrotic
      syndrome.
AB  - BACKGROUND: Prednisolone, the first-line treatment for children with nephrotic
      syndrome, causes severe side effects. One of these side effects is ocular
      hypertension, which can result in severe and permanent visual disturbance.
      However, the exact prevalence, severity and timing of development of ocular
      hypertension have yet to be fully explored in this pediatric patient group.
      METHODS: In this retrospective cohort study, children with nephrotic syndrome
      treated with prednisolone for their first episode were analyzed. Intraocular
      pressure was screened with an iCare(r) tonometer and confirmed with Goldmann
      applanation tonometry before the initiation of prednisolone treatment and at 1
      and 4 weeks thereafter. RESULTS: A total of 26 children with nephrotic syndrome
      were included in this study, of whom eight (30.8 %) required treatment with eye
      drops for ocular hypertension. The median time interval between the diagnosis of
      ocular hypertension and start of treatment was 9 (range 5-31) days. At relapse of
      nephrotic syndrome, all children who had undergone treatment for ocular
      hypertension in their first episode again required treatment for ocular
      hypertension. CONCLUSIONS: Routine ophthalmologic examination should be conducted
      from the early phase after the start of prednisolone treatment. In addition,
      children with episodes of ocular hypertension may be at greater risk of its
      reappearance with relapse of the nephrotic syndrome.

PMID- 24859791
TI  - Daidzein enhances efferocytosis via transglutaminase 2 and augmentation of Rac1
      activity.
AB  - Clearance of apoptotic cells, termed "efferocytosis", is the mechanism required
      to prevent secondary necrosis and release of proinflammatory cytokines. Defective
      efferocytosis is cumulatively regarded as one of mechanisms in the development of
      autoimmune and chronic inflammatory diseases. Our previous finding showed that
      ethanolic extract from Glycine tomentella Hayata (GTH) can enhance mouse
      macrophage RAW264.7 efferocytosis (clearance of apoptotic cells). We have
      demonstrated that the major components of GTH are daidzein, catechin, epicatechin
      and naringin. Here, we explore the potential of each component in modulating
      efferocytic capability. For this, RAW264.7 cells were cultured with CFDA-stained
      apoptotic cells and assayed by flow cytometry. We found that daidzein is the main
      component of GTH, and it can enhance RAW264.7 efferocytosis dose-dependently.
      Moreover, the enhancive effect of daidzein on macrophage efferocytic capability
      is accompanied by increased transglutaminase 2 (TG2) at both mRNA and protein
      levels. TG2 knockdown attenuated daidzein increased macrophage efferocytic
      capability. After treatment with daidzein, increased phosphorylation was observed
      in Erk, but not in p38 and JNK. Finally, we report that after daidzein treatment,
      Rac1 activity was markedly increased and the mitochondrial membrane potential was
      decreased, which may contribute to efferocytosis. Taken together, these data
      suggest that enhancement of macrophage efferocytic capability by daidzein
      treatment was mainly through up-regulation of TG2 expression and Rac1 activity.
      Daidzein may have the therapeutical potential in the treatment of inflammatory
      diseases.

PMID- 24859792
TI  - Chemokine expression profile of freshly isolated human glioblastoma-associated
      macrophages/microglia.
AB  - Several studies have substantiated the hypothesis that tumor progression is not
      only driven by the tumor cells themselves but also by their interaction with
      intrinsic and surrounding stromal cells. Tumor-associated macrophages and
      microglial cells (TAMs) represent one major stromal cell component of
      glioblastomas. Additionally, in many gliomas, chemokines are highly expressed and
      some chemokines were already linked to settlement of TAMs in tumors. However,
      although chemoattraction mechanisms mediated by chemokines and their receptors
      are well documented, information on their expression and role in TAMs,
      particularly in patients, is limited. Therefore, we investigated the
      transcription of the chemokine-receptor combinations CXCL12-CXCR4-CXCR7, CXCL16
      CXCR6 and CX3CL1-CX3CR1 in freshly isolated TAMs from 20 human glioblastomas in
      relation to in vitro polarized M1- and M2-macrophages. We demonstrated that TAMs
      express both M1- and M2-markers. Compared to in vitro polarized macrophages, the
      M1-marker interleukin (IL)-6 was similarly expressed, whereas IL-1beta and tumor
      necrosis factor (TNF)-alpha were found at lower levels. The M2-marker IL-10 was
      comparably expressed, while CD163 and transforming growth factor (TGF)-beta were
      detected with one tenth lower intensities in TAMs. All investigated
      chemokines/receptors were transcribed at moderate to high levels in TAMs as well
      as in vitro polarized macrophages. However, CX3CR1 was markedly higher and CXCR7
      was somewhat higher expressed in TAMs, whereas M2-macrophages were characterized
      by the highest CXCL12 and a moderate CX3CL1 expression. Collectively, TAMs share
      properties of M1- and M2-macrophages and show a considerably higher expression of
      the chemokine receptors CXCR7 and CX3CR1.

PMID- 24859793
TI  - Heparin induced dimerization of APP is primarily mediated by E1 and regulated by
      its acidic domain.
AB  - The amyloid precursor protein (APP) and its cellular processing are believed to
      be centrally involved in the etiology of Alzheimer's disease (AD). In addition,
      many physiological functions have been described for APP, including a role in
      cell-cell- and cell-ECM-adhesion as well as in axonal outgrowth. We show here the
      molecular determinants of the oligomerization/dimerization of APP, which is
      central for its cellular (mis)function. Using size exclusion chromatography
      (SEC), dynamic light scattering and SEC-coupled static light scattering we
      demonstrate that the dimerization of APP is energetically induced by a heparin
      mediated dimerization of the E1 domain, which results in a dimeric interaction of
      E2. We also show that the acidic domain (AcD) interferes with the dimerization of
      E1 and propose a model where both, cis- and trans-dimerization occur dependent on
      cellular localization and function. 

PMID- 24859794
TI  - M-free: scoring the reference bias in sub-tomogram averaging and template
      matching.
AB  - Cryo-electron tomography provides a snapshot of the cellular proteome. With
      template matching, the spatial positions of various macromolecular complexes
      within their native cellular context can be detected. However, the growing
      awareness of the reference bias introduced by the cross-correlation based
      approaches, and more importantly the lack of a reliable confidence measurement in
      the selection of these macromolecular complexes, has restricted the use of these
      applications. Here we propose a heuristic, in which the reference bias is
      measured in real space in an analogous way to the R-free value in X-ray
      crystallography. We measure the reference bias within the mask used to outline
      the area of the template, and do not modify the template itself. The heuristic
      works by splitting the mask into a working and a testing area in a volume ratio
      of 9:1. While the working area is used during the calculation of the cross
      correlation function, the information from both areas is explored to calculate
      the M-free score. We show using artificial data, that the M-free score gives a
      reliable measure for the reference bias. The heuristic can be applied in template
      matching and in sub-tomogram averaging. We further test the applicability of the
      heuristic in tomograms of purified macromolecules, and tomograms of whole
      Mycoplasma cells. 

PMID- 24859795
TI  - Validation of a bladder symptom screening tool in women with incontinence due to
      overactive bladder.
AB  - INTRODUCTION AND HYPOTHESIS: The Actionable Bladder Symptom Screening Tool
      (ABSST) was initially developed to identify patients with multiple sclerosis (MS)
      who could benefit from lower urinary tract assessment and treatment. Assessment
      of the measurement properties of the ABSST, including its ability to identify
      patients experiencing bladder symptoms related to overactive bladder (OAB), was
      undertaken in a general female population. METHODS: One hundred women completed
      the ABSST, OAB Questionnaire Short Form (OAB-q SF), and a patient global
      impression of severity (PGI-S) scale. Half of the sample had urgency urinary
      incontinence (UUI), while the other half did not. Descriptive statistics,
      reliability, and validity were examined, as was sensitivity and specificity of
      the previous cut-off score established in MS. RESULTS: Fifty-three women with
      UUI/OAB and 47 controls took part (71.0 % Caucasian). Patients with UUI/OAB were
      older (54.6 vs 40.4 years), had a higher body mass index (31.1 vs 26.4 kg/m(2)),
      and more comorbid conditions. The Cronbach's alpha reliability of ABSST was 0.90.
      High correlations with OAB-q SF Symptom Bother and Health Related Quality of Life
      (r = 0.83 and -0.81 respectively) supported concurrent validity. Using the PGI-S
      severity scores as a reference, the ABSST was able to distinguish patients with
      differing severity levels (known-group validity). Physician assessment of the
      need for further evaluation/treatment showed sensitivity (79 %) and specificity
      (98 %), supporting a cut-off score of >=3. CONCLUSIONS: The previous MS ABSST
      scoring algorithm was validated in a non-neurogenic female population. ABSST is a
      reliable, valid, and sensitive tool for screening women with UUI/OAB.

PMID- 24859796
TI  - Agreement between palpation and transperineal and endovaginal ultrasound in the
      diagnosis of levator ani avulsion.
AB  - INTRODUCTION AND HYPOTHESIS: Our aim was to estimate agreement between
      transperineal and endovaginal ultrasound in assessing levator ani biometry and
      avulsion in nullipara and primipara women and determine agreement between levator
      avulsion palpation and ultrasound. METHODS: This longitudinal cohort study
      assessed 269 nullipara women at 36 weeks gestation and 191 primipara women 13
      weeks postpartum. Women underwent levator palpation, and avulsion was diagnosed
      if no attachment to the pubic bone was felt. Subsequently, 3/4D transperineal and
      3D endovaginal ultrasound were performed. A standardized protocol was used to
      perform measurements at rest. Levator avulsion was diagnosed on endovaginal
      ultrasound at rest if >50 % was avulsed and on transperineal tomographic
      ultrasound imaging at maximum contraction if the central three slices were
      avulsed. Levator avulsion was analyzed by two independent, blinded investigators.
      A third investigator resolved discrepancies. Intraclass correlation coefficient
      and limits of agreement were calculated for each time point. RESULTS: Intraclass
      correlation coefficient for levator urethra gap was 0.44-0.54, hiatus area 0.76
      0.79, transverse diameter 0.51-0.59, anteroposterior diameter 0.70-0.72. Levator
      thickness correlated poorly. Endovaginal ultrasound measurements were generally
      smaller; however limits of agreement were acceptable for hiatus measurements.
      Overall agreement between both ultrasound techniques in diagnosing levator
      avulsion was 95 %; correlation 0.72 [95 % confidence interval (CI) 0.67-0.76].
      Agreement between palpation and transperineal ultrasound was 92 % (kappa = 0.34),
      and between palpation and endovaginal ultrasound was 92 % (kappa = 0.37).
      CONCLUSIONS: Transperineal and endovaginal ultrasound can both be used to analyze
      hiatus area and anteroposterior diameter with the patient at rest and to diagnose
      levator avulsion. Palpation correlates only fairly with both methods.

PMID- 24859797
TI  - A mutant BRAF V600E-specific immunohistochemical assay: correlation with
      molecular mutation status and clinical outcome in colorectal cancer.
AB  - The B-type Raf kinase (BRAF) V600E mutation is a well-established biomarker for
      poor prognosis in metastatic colorectal cancer (mCRC) and is a highly attractive
      drug target. A barrier to the development of new therapies targeting BRAF V600E
      in mCRC is the low prevalence of mutations (approximately 10 %) and the current
      need for access to sequencing-based technologies which are not routinely
      available outside of large cancer centres. Availability of a standardised
      immunohistochemistry (IHC) test, more suited to routine pathology practice, would
      provide much broader access to patient identification. We sought to evaluate the
      accuracy and clinical utility of a recently developed BRAF V600E IHC method as a
      prognostic biomarker in a large cohort of community-based CRC patients. Archival
      tumour samples from 505 patients with stage I-IV CRC were immunohistochemically
      tested with two antibodies, pBR1 for total BRAF and VE1 for BRAF V600E. Cases
      were assessed by two blinded pathologists, and results were compared to BRAF
      V600E mutation status determined using DNA sequencing. Discordant cases were
      retested with a BRAF V600E SNaPshot assay. BRAF mutation status was correlated
      with overall survival (OS) in stage IV CRC. By DNA sequencing and IHC, 505 and
      477 patients were respectively evaluable. Out of 477 patients, 56 (11. 7 %) had
      BRAF V600E mutations detected by sequencing and 63 (13.2 %) by IHC. Using DNA
      sequencing results as the reference, sensitivity and specificity for IHC were
      98.2 % (55/56) and 98.1 % (413/421), respectively. IHC had a positive predictive
      value (PPV) of 87.3 % (55/63) and a negative predictive value (NPV) of 99.8 %
      (413/414). Compared to DNA sequencing plus retesting of available discordant
      cases by SNaPshot assay, IHC using the VE1 antibody had a 100 % sensitivity
      (59/59), specificity (416/416), NPV (416/416) and PPV (59/59). Stage IV CRC
      patients with BRAF V600E protein detected by IHC exhibited a significantly
      shorter overall survival (hazard ratio = 2.20, 95 % CI 1.26-3.83, p = 0.005),
      consistent with other published series. Immunohistochemistry using the BRAF V600E
      VE1 antibody is an accurate diagnostic assay in CRC. The test provides a simple,
      clinically applicable method of testing for the BRAF V600E mutation in routine
      practice. 

PMID- 24859798
TI  - Early skin toxicity predicts better outcomes, and early tumor shrinkage predicts
      better response after cetuximab treatment in advanced colorectal cancer.
AB  - Cetuximab-containing treatments for metastatic colorectal cancer have been shown
      to have higher overall response rates and longer progression-free and overall
      survival than other systemic therapies. Cetuximab-related manifestations,
      including severe skin toxicity and early tumor shrinkage, have been shown to be
      predictors of response to cetuximab. We hypothesized that early skin toxicity is
      a predictor of response and better outcomes in patients with advanced colorectal
      carcinoma. We retrospectively evaluated 62 patients with colorectal
      adenocarcinoma who had unresectable tumors and were treated with cetuximab in our
      institution. Skin toxicity grade was evaluated on each treatment day. Tumor size
      was evaluated using computed tomography prior to treatment and 4-8 weeks after
      the start of treatment with cetuximab.Patients with early tumor shrinkage after
      starting treatment with cetuximab had a significantly higher overall response
      rate (P = 0.0001). Patients with early skin toxicity showed significantly longer
      overall survival (P = 0.0305), and patients with higher skin toxicity grades had
      longer progression-free survival (P = 0.0168).We have shown that early tumor
      shrinkage, early onset of skin toxicity, and high skin toxicity grade are
      predictors of treatment efficacy and/or outcome in patients with advanced
      colorectal carcinoma treated with cetuximab. 

PMID- 24859799
TI  - Electrical detection of cellular penetration during microinjection with carbon
      nanopipettes.
AB  - The carbon nanopipette (CNP) is comprised of a pulled-glass pipette terminating
      with a nanoscale (tens to hundreds of nm) diameter carbon pipe. The entire inner
      glass surface of the CNP is coated with a carbon film, providing an electrically
      conductive path from the carbon tip to the distal, macroscopic end of the
      pipette. The CNP can double as a nanoelectrode, enabling electrical measurements
      through its carbon lining, and as a nanoinjector, facilitating reagent injection
      through its hollow bore. With the aid of a lock-in amplifier, we measured, in
      real time and with millisecond resolution, variations in impedance and
      interfacial capacitance as the CNP penetrated into the cytoplasm and nucleus of
      adherent human osteosarcoma (U20S) cells during microinjection. The capacitance
      change associated with nucleus penetration was, on average, 1.5 times greater
      than the one associated with cell membrane penetration. The experimental data was
      compared and favorably agreed with theoretical predictions based on a simple
      electrical network model. As a proof of concept, the cytoplasm and nucleus were
      transfected with fluorescent tRNA, enabling real-time monitoring of tRNA
      trafficking across the nuclear membrane. The CNP provides a robust and reliable
      means to detect cell and nucleus penetration, and trigger injection, thereby
      enabling the automation of cell injection.

PMID- 24859801
TI  - Extracellular disulfide bridges stabilize TRPC5 dimerization, trafficking, and
      activity.
AB  - Crucial cysteine residues can be involved in the modulation of protein activity
      via the modification of thiol (-SH) groups. Among these reactions, disulfide
      bonds (S-S) play a key role in the folding, stability, and activity of membrane
      proteins. However, the regulation of extracellular cysteines in classical
      transient receptor potential (TRPC) channels remains controversial. Here, we
      examine the functional importance of the extracellular disulfide bond in TRPC5 in
      modulating channel gating and trafficking. Specifically, we investigated TRPC5
      activity in transiently transfected HEK293 cells with wild-type (WT) or cysteine
      (C553 and C558) mutants in the pore loop. Using reducing agents, we determined
      that a disulfide linkage mediates the tetrameric formation of the TRPC5 channel.
      By measuring the TRPC5 current, we observed that C553S or C558S mutants
      completely lose channel activity induced by lanthanides or receptor stimulation.
      Co-expression of TRPC5 (WT) with mutants demonstrated a dominant-negative
      function in mutants, which inhibited the activity of TRPC5 (WT). We generated
      TRPC5-TRPC5 dimers and observed reduced activity of WT-mutant (C553S or C558S)
      dimers compared to WT-WT dimers. When pretreated with reducing agents for 12 h,
      the TRPC5 current decreased due to a reduction in membrane TRPC5 distribution. In
      addition, we identified a reduced expression of C553S mutant in plasma membrane.
      We analyzed a dimeric interaction of wild-type and mutant TRPC5 using co
      immunoprecipitation and FRET method, indicating a weak interaction between
      dimeric partners. These results indicated that the disulfide bond between
      conserved extracellular cysteines, especially C553, is essential for functional
      TRPC5 activity by channel multimerization and trafficking.

PMID- 24859802
TI  - Safety and Efficacy of Single-site Phacotrabeculectomy With Mitomicin C Using
      Nylon and Polyglactin Suture for Scleral Tunnel Closure.
AB  - PURPOSE: To evaluate the efficacy of polyglactin use along with nylon suture in
      scleral tunnel closure after single-site phacotrabeculectomy. METHODS: This
      retrospective case series included 139 eyes of 139 patients who had scleral
      tunnel closure with 1 polyglactin and 1 nylon suture after single-site
      phacotrabeculectomy with a low dose of mitomycin C between 2002 and 2005. The
      intraocular pressure (IOP), the visual acuity, the number of glaucoma
      medications, postoperative complications, and interventions were the outcomes
      measured. RESULTS: The majority of them had primary open-angle glaucoma (93 eyes,
      67%), 93 eyes (67%) had severe glaucomatous optic neuropathy, and 77 eyes (55.3%)
      had severe visual-field loss. The IOP decreased from a mean preoperative value of
      18.1+/-5.3 mm Hg on a mean number of 1.8+/-0.8 glaucoma medications to mean IOPs
      of 13.3+/-4.6, 14.0+/-4.3, and 11.8+/-3.9 mm Hg on a mean number of 0.2+/-0.6,
      0.3+/-0.7, 0.5+/-1.0 glaucoma medications (P<0.001) at 1-, 3-, and 5-year follow
      up visits, respectively. An IOP of <21 mm Hg with or without medication was
      achieved in 96+/-2% at 1 year, in 88+/-4% at 3 years, and in 73+/-8% at 5 years.
      Shallow anterior chamber was the most common early postoperative complication (3
      eyes, 2.1%). Nylon suturelysis with laser was performed in 16 eyes (11.5%).
      CONCLUSIONS: The technique used here seems to be effective in controlling the IOP
      and has very minimal associated complications.

PMID- 24859800
TI  - MscL: channeling membrane tension.
AB  - Mechanosensitive channels are integral components for the response of bacteria to
      osmotic shock. The mechanosensitive channel of large conductance (MscL) responds
      to extreme turgor pressure increase that would otherwise lyse the cellular
      membrane. MscL has been studied as a model mechanosensitive channel using both
      structural and functional approaches. We will summarize the structural data and
      discuss outstanding questions surrounding the gating mechanism of this homo
      oligomeric channel that has ~3 nS conductance. Specifically, we will explore the
      following: (1) the variability in oligomeric state that has been observed, (2)
      the open pore size measurements, and (3) the role of the C-terminal coiled coil
      domain for channel function. The oligomeric state of MscL has been characterized
      using various techniques, with a pentamer being the predominant form; however,
      the presence of mixtures of oligomers in the membrane is still uncertain. In the
      absence of structural data for the open state of MscL, the diameter of the open
      state pore has been estimated by several different approaches, leading to a
      current estimate between 25 and 30 A. While the C-terminal domain is highly
      conserved among MscL homologues, it is not required for activity in vivo or in
      vitro. This domain is likely to remain intact during the gating transition and
      perform a filtering function that retains valuable osmolytes in the cytosol.
      Overall, studies of MscL have provided significant insight to the field, and
      serve as a paradigm for the analysis of non-homologous, eukaryotic
      mechanosensitive channel proteins.

PMID- 24859803
TI  - Effect of voxel size when calculating patient specific radionuclide dosimetry
      estimates using direct Monte Carlo simulation.
AB  - The scalable XCAT voxelised phantom was used with the GATE Monte Carlo toolkit to
      investigate the effect of voxel size on dosimetry estimates of internally
      distributed radionuclide calculated using direct Monte Carlo simulation. A
      uniformly distributed Fluorine-18 source was simulated in the Kidneys of the XCAT
      phantom with the organ self dose (kidney <- kidney) and organ cross dose (liver <
      kidney) being calculated for a number of organ and voxel sizes. Patient specific
      dose factors (DF) from a clinically acquired FDG PET/CT study have also been
      calculated for kidney self dose and liver <- kidney cross dose. Using the XCAT
      phantom it was found that significantly small voxel sizes are required to achieve
      accurate calculation of organ self dose. It has also been used to show that a
      voxel size of 2 mm or less is suitable for accurate calculations of organ cross
      dose. To compensate for insufficient voxel sampling a correction factor is
      proposed. This correction factor is applied to the patient specific dose factors
      calculated with the native voxel size of the PET/CT study. 

PMID- 24859804
TI  - Risk factors for Barrett's esophagus.
AB  - PURPOSE OF REVIEW: To summarize the emerging data on the risk factors for
      Barrett's esophagus and risk stratification tools. RECENT FINDINGS: Obesity,
      particularly abdominal obesity, is associated with Barrett's esophagus, likely
      because of both mechanical effects promoting gastroesophageal reflux and
      nonmechanical effects. Circulating peptides related to obesity alter the risk of
      Barrett's esophagus and may work synergistically with gastroesophageal reflux.
      Tobacco use is an underappreciated risk for Barrett's esophagus. A number of
      genetic variants have been associated with Barrett's esophagus, involving
      pathways in esophageal development. Risk stratification tools are becoming
      available that have modest discriminatory capability and good calibration.
      SUMMARY: The developing understanding of risk factors for Barrett's esophagus is
      shifting the clinical guidelines to a nuanced approach incorporating multiple
      risk factors to select patients for screening for Barrett's esophagus.

PMID- 24859805
TI  - Combined impedance-manometry for the evaluation of esophageal disorders.
AB  - PURPOSE OF REVIEW: Combined impedance-manometry was introduced just over 20 years
      ago for the assessment of esophageal motor function. Since then, technical
      developments have led to the introduction of high-resolution impedance-manometry
      (HRIM). However, analysis of the impedance and manometry recordings has remained
      separate and relatively unchanged since the introduction of HRIM, and it is
      unclear whether the addition of impedance has had a significant impact on the
      management of esophageal motor disorders. RECENT FINDINGS: The major technical
      advance over the past 12 months or so has been the development of automated
      impedance-manometry (AIM) analysis, in which the impedance and manometric data
      are analyzed together to assess the interactions between pressure and flow. This
      analysis has revealed subtle abnormalities in esophageal function in patients
      with nonobstructive dysphagia who have normal manometry and conventional
      impedance analyses. AIM analysis has also revealed preoperative characteristics
      in patients that may predict the occurrence of postfundoplication dysphagia.
      SUMMARY: Through ongoing technical development, impedance-manometry is becoming
      increasingly useful clinically to assess esophageal motility disorders as well as
      to provide further insights into esophageal physiology.

PMID- 24859806
TI  - Development and Psychometric Assessment of the Measure of Globalization Influence
      on Health Risk (MGIHR) Among Mexican Women with Breast Cancer.
AB  - Lacking in the literature are data addressing the extent to which changes in
      reproductive and lifestyle factors predispose women in developing nations to
      higher breast cancer rates, and the degree to which these are due to
      globalization influences. This article describes the development and psychometric
      assessment of an instrument intended to measure global, predominantly U.S.,
      influences on breast cancer risk profile among women residing in Mexico. Using
      investigator consensus and a focus group methodology, the Measure of
      Globalization Influence on Health Risk (MGIHR) was developed and completed by 341
      women. Psychometric analysis support the use of an 11-item Consumerism and
      Modernity scale and 7-item Reproductive Control and Gender Role scale. The MGIHR
      is a valid and reliable instrument for understanding changing lifestyle and
      reproductive factors for breast cancer risk and may provide a more complete
      understanding of breast cancer development and needed interventions. 

PMID- 24859807
TI  - The incidence rate of thyroid cancer among women in Saudi Arabia: an
      observational descriptive epidemiological analysis of data from Saudi Cancer
      Registry 2001-2008.
AB  - This study provides a descriptive epidemiological data of thyroid cancer cases
      diagnosed from 2001 to 2008 among Saudi women, including the frequency and
      percentage of cases, the crude incidence rate (CIR) and the age-standardised
      incidence rate (ASIR) stratified by the region and year of diagnosis. This is a
      retrospective descriptive epidemiological analysis of all Saudi thyroid cancer
      cases recorded in the Saudi Cancer Registry (SCR) between January 2001 and
      December 2008. The statistical analyses were applied using descriptive statistics
      with the Statistical Package for the Social Sciences version 20.0. A total of
      2,930 cases were recorded in the SCR between January 2001 and December 2008. The
      region of Riyadh in Saudi Arabia had the highest overall ASIR at 9.43 per 100,000
      women, followed by Tabuk at 7.11 and eastern region at 6.5, while Jazan and Jouf
      had the lowest average ASIRs at 1.97 and at 2.72, respectively. The region of
      Qassim recorded the greatest changes of ASIR at 5.5 per 100,000 women from 2001
      to 2008. There was a slight increase in the CIRs and ASIRs for thyroid cancer in
      Saudi Arabia between 2001 and 2008. Riyadh, Tabuk and eastern region were the
      highest overall ASIR in Saudi Arabia. While, Jazan and Hail had the lowest rates.
      Finally, the region of Qassim had the highest changes in CIR and ASIR from 2001
      to 2008. Further analytical studies are needed to determine the potential risk
      factors of thyroid cancer disease among Saudi women. 

PMID- 24859808
TI  - Efficacy of switching from premixed insulin to insulin glargine regimen in Type 2
      diabetes mellitus patients with different islet functions.
AB  - The present study evaluated the efficacy of switching from premixed insulin or an
      insulin analogue to insulin glargine plus oral antidiabetic drugs (OADs) in
      patients with type 2 diabetes mellitus (T2DM). The feasibility and suitability of
      the regimen to the patients was examined based on islet function. Patients with
      T2DM (n=30) treated with stable doses of premixed insulin or an insulin analogue
      for eight weeks were divided into two groups according to islet function. Group A
      had a 2 h of C peptide (2hCP)/fasting C peptide (FCP) ratio <=3, whereas group B
      had a 2hCP/FCP ratio >3. Eight weeks following the switch to insulin glargine
      plus OADs, a significant decrease in fasting blood glucose (FBG), 2 h
      postprandial blood glucose (2hPBG) and glycosylated-haemoglobin (HbA1c) were
      observed in the two groups, with effective rates of 75, 42.9 and 39.3%,
      respectively. A distinct reduction in the insulin dose was particularly evident
      in group B. There was a marked decrease in FBG in group A, more so than that
      observed in group B. By contrast, the decrease in HbA1c was more evident in group
      B following the switch. A larger number of patients in group B had HbA1c<=7.0%,
      compared with group A. No difference in the incidence of hypoglycaemia and change
      of body weight were observed. Following the switch to insulin glargine plus OADs,
      patients with T2DM demonstrated improved blood glucose control and reduced
      insulin dosage. The results revealed that this switch in regimen is more suitable
      for patients with T2DM with 2hCP/FCP>3 and that administration of insulin
      glargine plus OADs is more efficacious for patients with T2DM with increased FBG
      levels. 

PMID- 24859809
TI  - Investigation of ptsG gene in response to xylose utilization in Corynebacterium
      glutamicum.
AB  - Corynebacterium glutamicum strains NC-2 were able to grow on xylose as sole
      carbon sources in our previous work. Nevertheless, it exhibited the major
      shortcoming that the xylose consumption was repressed in the presence of glucose.
      So far, regarding C. glutamicum, there are a number of reports on ptsG gene, the
      glucose-specific transporter, involved in glucose metabolism. Recently, we found
      ptsG had influence on xylose utilization and investigated the ptsG gene in
      response to xylose utilization in C. glutamicum with the aim to improve xylose
      consumption and simultaneously utilized glucose and xylose. The ptsG-deficient
      mutant could grow on xylose, while exhibiting noticeably reduced growth on xylose
      as sole carbon source. A mutant deficient in ptsH, a general PTS gene, exhibited
      a similar phenomenon. When complementing ptsG gene, the mutant DeltaptsG-ptsG
      restored the ability to grow on xylose similarly to NC-2. These indicate that
      ptsG gene is not only essential for metabolism on glucose but also important in
      xylose utilization. A ptsG-overexpressing recombinant strain could not accelerate
      glucose or xylose metabolism. When strains were aerobically cultured in a sugar
      mixture of glucose and xylose, glucose and xylose could not be utilized
      simultaneously. Interestingly, the DeltaptsG strain could co-utilize glucose and
      xylose under oxygen-deprived conditions, though the consumption rate of glucose
      and xylose dramatically declined. It was the first report of ptsG gene in
      response to xylose utilization in C. glutamicum. 

PMID- 24859810
TI  - MST4 promotes hepatocellular carcinoma epithelial-mesenchymal transition and
      metastasis via activation of the p-ERK pathway.
AB  - Mammalian sterile-20-like kinase 4 (MST4) has been implicated in cell
      proliferation and differentiation. In a previous study, we found MST4 to be an
      important candidate gene for metastatic hepatocellular carcinoma (HCC); however,
      the molecular mechanism of the promoting role of MST4 in HCC metastasis is poorly
      understood. In this study, we show that high expression of MST4 was detected in
      highly invasive HCC cells and in human HCC specimens with vascular invasion. A
      high level of MST4, associated with large tumor size, microvascular invasion,
      presence of intrahepatic metastasis, and advanced TNM classification of malignant
      tumors stage, was an independent prognostic factor for overall survival (P=0.004)
      and time to recurrence (P=0.001) after hepatectomy. Knockdown of MST4 expression
      in HCC cells inhibited cell proliferation, colony formation, and invasion,
      whereas upregulation of MST4 significantly promoted these processes by promoting
      epithelial-mesenchymal transition (EMT), dependent on the activation of
      extracellular signal-regulated protein kinase (ERK) signaling pathways.
      Furthermore, the combination of MST4 and phosphorylated ERK was proven to have
      more power to predict the outcomes of HCC patients. This study presents clinical
      evidence for predicting the value of MST4 in HCC overall survival and recurrence
      and describes the key role of MST4 in facilitating the EMT process via regulating
      the activation of ERK, indicating its potential role as a target for
      postoperative adjuvant therapy for HCC. 

PMID- 24859811
TI  - Anti-L1CAM radioimmunotherapy is more effective with the radiolanthanide terbium
      161 compared to lutetium-177 in an ovarian cancer model.
AB  - PURPOSE: The L1 cell adhesion molecule (L1CAM) is considered a valuable target
      for therapeutic intervention in different types of cancer. Recent studies have
      shown that anti-L1CAM radioimmunotherapy (RIT) with (67)Cu- and (177)Lu-labelled
      internalising monoclonal antibody (mAb) chCE7 was effective in the treatment of
      human ovarian cancer xenografts. In this study, we directly compared the
      therapeutic efficacy of anti-L1CAM RIT against human ovarian cancer under
      equitoxic conditions with the radiolanthanide (177)Lu and the potential
      alternative (161)Tb in an ovarian cancer therapy model. METHODS: Tb was produced
      by neutron bombardment of enriched (160)Gd targets. (161)Tb and (177)Lu were used
      for radiolabelling of DOTA-conjugated antibodies. The in vivo behaviour of the
      radioimmunoconjugates (RICs) was assessed in IGROV1 tumour-bearing nude mice
      using biodistribution experiments and SPECT/CT imaging. After ascertaining the
      maximal tolerated doses (MTD) the therapeutic impact of 50 % MTD of (177)Lu- and
      (161)Tb-DOTA-chCE7 was evaluated in groups of ten mice by monitoring the tumour
      size of subcutaneous IGROV1 tumours. RESULTS: The average number of DOTA ligands
      per antibody was 2.5 and maximum specific activities of 600 MBq/mg were achieved
      under identical radiolabelling conditions. RICs were stable in human plasma for
      at least 48 h. (177)Lu- and (161)Tb-DOTA-chCE7 showed high tumour uptake (37.8
      39.0 %IA/g, 144 h p.i.) with low levels in off-target organs. SPECT/CT images
      confirmed the biodistribution data. (161)Tb-labelled chCE7 revealed a higher
      radiotoxicity in nude mice (MTD: 10 MBq) than the (177)Lu-labelled counterpart
      (MTD: 12 MBq). In a comparative therapy study with equitoxic doses, tumour growth
      inhibition was better by 82.6 % for the (161)Tb-DOTA-chCE7 than the (177)Lu-DOTA
      chCE7 RIT. CONCLUSIONS: Our study is the first to show that anti-L1CAM (161)Tb
      RIT is more effective compared to (177)Lu RIT in ovarian cancer xenografts. These
      results suggest that (161)Tb is a promising candidate for future clinical
      applications in combination with internalising antibodies.

PMID- 24859812
TI  - Lossless directional guiding of light in dielectric nanosheets using Dyakonov
      surface waves.
AB  - Guiding light at the nanoscale is usually accomplished using surface plasmons.
      However, plasmons propagating at the surface of a metal sustain propagation
      losses. A different type of surface excitation is the Dyakonov surface wave.
      These waves, which exist in lossless media, were predicted more than two decades
      ago but observed only recently. Dyakonov surface waves exist when at least one of
      the two media forming the surface exhibits a suitable anisotropy of refractive
      indexes. Although propagating only within a narrow range of directions, these
      waves can be used to create modes supported by ultrathin films that confine light
      efficiently within film thicknesses well below the cutoff thickness required in
      standard waveguides. Here, we show that 10 nm and 20 nm dielectric nanosheets of
      aluminium oxide clad between an anisotropic crystal (lithium triborate) and
      different liquids support Dyakonov-like modes. The direction of light propagation
      can be controlled by modulating the refractive index of the cladding. The
      possibility of guiding light in nanometre-thick films with no losses and high
      directionality makes Dyakonov wave modes attractive for planar photonic devices
      in schemes similar to those currently employing long-range plasmons.

PMID- 24859814
TI  - Nano-optics: Steering Dyakonov-like waves.

PMID- 24859813
TI  - Multi-enzyme complexes on DNA scaffolds capable of substrate channelling with an
      artificial swinging arm.
AB  - Swinging arms are a key functional component of multistep catalytic
      transformations in many naturally occurring multi-enzyme complexes. This arm is
      typically a prosthetic chemical group that is covalently attached to the enzyme
      complex via a flexible linker, allowing the direct transfer of substrate
      molecules between multiple active sites within the complex. Mimicking this method
      of substrate channelling outside the cellular environment requires precise
      control over the spatial parameters of the individual components within the
      assembled complex. DNA nanostructures can be used to organize functional
      molecules with nanoscale precision and can also provide nanomechanical control.
      Until now, protein-DNA assemblies have been used to organize cascades of
      enzymatic reactions by controlling the relative distance and orientation of
      enzymatic components or by facilitating the interface between enzymes/cofactors
      and electrode surfaces. Here, we show that a DNA nanostructure can be used to
      create a multi-enzyme complex in which an artificial swinging arm facilitates
      hydride transfer between two coupled dehydrogenases. By exploiting the
      programmability of DNA nanostructures, key parameters including position,
      stoichiometry and inter-enzyme distance can be manipulated for optimal activity. 

PMID- 24859815
TI  - Neural correlates underlying true and false associative memories.
AB  - Despite the fact that associative memory studies produce a large number of false
      memories, neuroimaging analyses utilizing this paradigm typically focus only on
      neural activity mediating successful retrieval. The current study sought to
      expand on this prior research by examining the neural basis of both true and
      false associative memories. Though associative false memories are substantially
      different than those found in semantic or perceptual false memory paradigms,
      results suggest that associative false memories are mediated by similar neural
      mechanisms. Specifically, we found increased frontal activity that likely
      represents enhanced monitoring and evaluation compared to that needed for true
      memories and correct rejections. Results also indicated that true, and not false
      associative memories, are mediated by neural activity in the MTL, specifically
      the hippocampus. Finally, while activity in early visual cortex distinguished
      true from false memories, a lack of neural differences between hits and correct
      rejections failed to support previous findings suggesting that activity in early
      visual cortex represents sensory reactivation of encoding-related processing. 

PMID- 24859816
TI  - Changes in serum copper and zinc levels in peripartum healthy and subclinically
      hypocalcemic dairy cows.
AB  - The objective of this study was to determine the levels of serum copper and zinc
      in subclinically hypocalcemic peripartum dairy cows in comparison to healthy
      animals. Blood samples were taken from 219 multiparous Holstein cows near
      parturition (from 4 weeks prepartum to 4 weeks postpartum) and 51 cows with
      subclinical hypocalcemia. The results showed that the serum copper concentration
      increased gradually at 1 week prepartum and remained high for the first 4 weeks
      postpartum in the healthy periparturient dairy cows. The serum zinc concentration
      reached a nadir at 1 week postpartum and subsequently increased gradually to
      baseline. The serum zinc concentration was significantly decreased (P<0.01) in
      dairy cows with subclinical hypocalcemia compared with healthy cows. There was no
      significant difference in the serum copper concentration between cows with
      subclinical hypocalcemia and healthy cows. These data demonstrate that the
      concentrations of copper and zinc in serum change dramatically during the
      peripartum period in dairy cows, which is a tremendous challenge for the body and
      for the maintenance of dairy cow health. The present study further suggests that
      a decreased serum zinc concentration could be a cause of decreased productive
      performance and increased susceptibility to other diseases due to
      immunosuppression in dairy cows with subclinical hypocalcemia. Additionally, this
      decreased zinc concentration may be involved in the pathogenesis of subclinical
      hypocalcemia.

PMID- 24859817
TI  - Remote sensing of sample temperatures in nuclear magnetic resonance using
      photoluminescence of semiconductor quantum dots.
AB  - Knowledge of sample temperatures during nuclear magnetic resonance (NMR)
      measurements is important for acquisition of optimal NMR data and proper
      interpretation of the data. Sample temperatures can be difficult to measure
      accurately for a variety of reasons, especially because it is generally not
      possible to make direct contact to the NMR sample during the measurements. Here I
      show that sample temperatures during magic-angle spinning (MAS) NMR measurements
      can be determined from temperature-dependent photoluminescence signals of
      semiconductor quantum dots that are deposited in a thin film on the outer surface
      of the MAS rotor, using a simple optical fiber-based setup to excite and collect
      photoluminescence. The accuracy and precision of such temperature measurements
      can be better than +/-5K over a temperature range that extends from approximately
      50K (-223 degrees C) to well above 310K (37 degrees C). Importantly, quantum dot
      photoluminescence can be monitored continuously while NMR measurements are in
      progress. While this technique is likely to be particularly valuable in low
      temperature MAS NMR experiments, including experiments involving dynamic nuclear
      polarization, it may also be useful in high-temperature MAS NMR and other forms
      of magnetic resonance. 

PMID- 24859818
TI  - Extensive training extends numerical abilities of guppies.
AB  - Recent studies on animal mathematical abilities suggest that all vertebrates show
      comparable abilities when they are given spontaneous preference tests, such as
      selecting the larger number of food items, but that mammals and birds generally
      achieve much better performance than fish when tested with training procedures.
      At least part of these differences might be due to the fact that fish are usually
      trained with only one or two dozen trials while extensive training, sometimes
      with thousands of trials, is normally performed in studies of mammals and birds.
      To test this hypothesis, female guppies were trained on four consecutive
      numerical discriminations of increasing difficulty (from 2 vs. 3 to 5 vs. 6
      items), with up to 120 trials with each discrimination. Five out of eight
      subjects discriminated all contrasts up to 4 versus 5 objects at levels
      significantly better than chance, a much higher limit than the 2 versus 3 limit
      previously reported in studies that provided fish with only short training
      sequences. Our findings indicate that the difference in numerical cognition
      between teleosts and warm-blooded vertebrates might be smaller than previously
      supposed. 

PMID- 24859819
TI  - Cerebral small artery diseases may be associated with aortic arch calcification
      in stroke patients.
AB  - AIM: Aortic arch calcification (AoAC) on chest X-rays represents systemic
      atherosclerosis and it is associated with ischemic cardiovascular diseases.
      However, the relationship between ischemic stroke and AoAC has yet to be fully
      elucidated. METHODS: Patients with acute ischemic stroke who were undergoing
      chest X-ray, blood, and brain magnetic resonance imaging (MRI) examinations were
      prospectively studied. The extent of AoAC on chest X-ray was divided into four
      grades (0-3). Clinical characteristics, biochemical findings, white matter
      lesions on MRI, and AoAC extent were assessed in each stroke subtype, and the
      factors associated with AoAC were investigated. RESULTS: A total of 175 patients
      (age, 70 +/- 13 years; 115 men) were enrolled in the study. According to the
      Trial of Org 10172 in Acute Stroke Treatment classification with minor
      modification, 33 patients (19%) had small artery occlusion (SAO), 42 (24%) had
      large artery atherosclerosis, 49 (28%) had cardioembolism, 24 (14%) had stroke
      with other determined etiologies, and 27 (17%) had stroke with undetermined
      etiologies. Compared to other stroke subtypes, the extent of AoAC was
      independently correlated with SAO (all p<0.05). Age (odds ratio [OR]: 1.14, 95%
      confidence interval [CI]: 1.08 to 1.19, p<0.001), hypertension, (OR: 3.44, 95%
      CI: 1.23 to 9.66, p=0.019), diabetes mellitus (OR: 2.19, 95% CI: 0.99 to 4.85,
      p=0.054), white matter lesions (OR: 1.54, 95% CI: 1.00 to 2.36, p=0.048), and SAO
      (OR: 1.38, 95% CI: 1.02 to 1.89, p=0.040) were significantly associated with
      AoAC. CONCLUSIONS: Age, hypertension, cerebral small artery disease, and possibly
      diabetes mellitus appear to be closely associated with AoAC in patients with
      acute ischemic stroke.

PMID- 24859820
TI  - Cord blood 25(OH)D levels and the subsequent risk of lower respiratory tract
      infections in early childhood: the Ulm birth cohort.
AB  - Lower respiratory tract infections (LRTIs) are a major cause of hospitalization
      in infants. Research suggests that immunomodulatory properties of vitamin D may
      influence LRTI risk. This study's objective was to examine whether 25
      hydroxyvitamin D [25(OH)D] concentrations in cord blood influenced susceptibility
      to LRTI in the first year of life. Data was analyzed from a prospective birth
      cohort of 777 mother-infant pairs based in Ulm, Germany. Relative risks (RRs) of
      LRTI in relation to 25(OH)D cord blood levels were estimated by log-binomial
      regression after adjustment for potential confounders. To account for seasonal
      variation in both vitamin D levels and infections, we examined the association in
      different seasons. Analyses were conducted using clinical predefined cutpoints,
      quartiles, and season-standardized 25(OH)D quartiles. We observed a statistically
      significant association between 25(OH)D status in cord blood and risk of LRTI
      across the year using clinical cutpoints. The adjusted RR of LRTI for individuals
      with vitamin D deficiency (<25 nmol/L) in comparison to the referent category
      (>50 nmol/L) was 1.32 [95 % confidence interval (CI) 1.00, 1.73]. The association
      differed by maternal allergy status; children born to mothers without allergy
      demonstrated a RR of 1.45 (95 % CI 1.03, 2.03). The effect was largely driven by
      a strong association between 25(OH)D and LRTI in infants born in fall with a RR
      of 3.07 (95 % CI 1.37, 6.87). Our findings suggest that vitamin D deficiency at
      birth is associated with increased risk of LRTI particularly in infants born to
      mothers without allergy. The association seems strongest in infants born in fall.

PMID- 24859821
TI  - Characterization of fibromyalgia symptoms in patients 55-95 years old: a
      longitudinal study showing symptom persistence with suboptimal treatment.
AB  - BACKGROUND: Fibromyalgia (FM) has been understudied in the elderly population, a
      group with particular vulnerabilities to pain, reduced mobility, and sleep
      disruption. AIMS: To characterize FM symptoms and treatments in a cohort of older
      subjects examined over time to determine the extent to which current, community
      based treatment for older FM patients is in accord with published guidelines, and
      effective in reducing symptoms. METHODS: A longitudinal, observational study of
      51 subjects with FM (range 55-95 years) and 81 control subjects (58-95 years)
      performed at Banner Sun Health Research Institute in Sun City, AZ, USA. Serial
      history and examination data were obtained over a 6-year period. FM data included
      medical history, medications, physical examination, tender point examination,
      neuropsychological testing, sleep and pain ratings, the Physical Function
      Subscale of the Fibromyalgia Impact Questionnaire, and other standardized scales
      to evaluate depression and other psychiatric symptoms, and cognitive and
      functional impairment. RESULTS: Pain and stiffness that interfered with physical
      activity, sleep, and mood were reported by 80 % or more of subjects. Over time,
      pain involved an increasing number of body areas. Over half of subjects were
      treated with NSAIDs, one-quarter with opioids, and one-quarter with estrogen. Few
      were treated with dual-acting antidepressants or pregabalin. DISCUSSION: In this
      cohort of elders with suboptimally treated FM, substantial persistence of
      symptoms was seen over time. In general, recommended treatments were either not
      used or not tolerated. CONCLUSIONS: Age-appropriate treatments as well as
      education of primary care providers are needed to improve treatment of FM in the
      older population.

PMID- 24859822
TI  - Hormonal profiles, physiological parameters, and productive and reproductive
      performances of Girolando cows in the state of Ceara-Brazil.
AB  - This study compared two breed groups of Girolando (1/2 Holstein 1/2 Gyr vs. 3/4
      Holstein 1/4 Gyr) through analysis of physiological, productive, and reproductive
      parameters to determine the group best suited to rearing in a semiarid tropical
      climate. The experiment was conducted at the Companhia de Alimentos do Nordeste
      (CIALNE) farm, in the municipality of Umirim, State of Ceara, Brazil. Eighty cows
      were used in a 2 * 2 factorial study; 40 of each breed group were kept under an
      extensive system during the wet season and an intensive system during the dry
      season. The collection of physiological data and blood samples were obtained in
      the afternoon after milking. Rectal temperature (RT), surface temperature (ST),
      and respiratory rate (RR) were obtained for each cow after milking. Blood samples
      were obtained by tail vein puncture and were determined triiodothyronine (T3) and
      thyroxine (T4) and cortisol. The environmental parameters obtained were relative
      humidity (RH) and air temperature (AT), and from these, a temperature and
      humidity index (THI) was calculated. Pregnancy diagnosis (PD) was determined by
      ultrasonography 30 days after artificial insemination (AI). The milk production
      of each cow was recorded with automated milkings in the farm. The variables were
      expressed as mean and standard error, evaluated by ANOVA at 5% probability using
      the Proc GLM of SAS. Chi-square test at 5% probability was applied to data of
      pregnancy rate (PR) and the number of AI's to obtain pregnancy. It can be
      concluded that the breed group 1/2 Holstein 1/2 Gyr is most suited for farming
      under conditions of thermal stress.

PMID- 24859824
TI  - 3D strain measurement in electronic devices using through-focal annular dark
      field imaging.
AB  - Spherical aberration correction in high-angle annular dark-field scanning
      transmission electron microscopy (HAADF-STEM) allows us to form an electron probe
      with reduced depth of field. Using through-focal HAADF imaging, we experimentally
      demonstrated 3D strain measurement in a strained-channel transistor. The strain
      field distribution in the channel region was obtained by scanning an electron
      beam over a plan-view specimen. Furthermore, the decrease in the strain fields
      toward the silicon substrate was revealed at different focal planes with a 5-nm
      focal step. These results demonstrate that it is possible to reconstruct the 3D
      strain field in electronic devices. 

PMID- 24859823
TI  - Structural aspects of dog allergies: the crystal structure of a dog dander
      allergen Can f 4.
AB  - Four out of six officially recognized dog allergens are members of the lipocalin
      protein family. So far, a three-dimensional structure has been determined for
      only one dog allergen, Can f 2, which is a lipocalin protein. We present here the
      crystal structure of a second lipocalin allergen from dog, a variant of Can f 4.
      Moreover, we have compared and analyzed the structures of these two weakly
      homologous (amino acid identity 21%) dog allergens. The size and the amino acid
      composition of the ligand-binding pocket indicate that Can f 4 is capable of
      binding only relatively small hydrophobic molecules which are different from
      those that Can f 2 is able to bind. The crystal structure of Can f 4 contained
      both monomeric and dimeric forms of the allergen, suggesting that Can f 4 is able
      to form transient (weak) dimers. The existence of transient dimers in solution
      was confirmed by use of native mass spectrometry. The dimeric structure of Can f
      4 is formed when the ends of four beta-strands are packed against the same
      strands from the second monomer. The residues in the interface are mainly
      hydrophobic and the formation of the dimer is similar to the major horse allergen
      Equ c 1. Interestingly, the crystal structure of dog Can f 2 has been reported to
      show a different type of dimer formation. The capability of these allergens to
      form dimers may be important for the development of immediate allergic reaction
      (mast cell activation) because oligomeric allergens can effectively present
      multivalent epitopes. 

PMID- 24859825
TI  - N-benzyl-N-methyldecan-1-amine, a phenylamine derivative isolated from garlic
      cloves, induces G2/M phase arrest and apoptosis in U937 human leukemia cells.
AB  - Epidemiological studies indicate that components of garlic (Allium sativum) have
      anti-proliferative effects against various types of cancer. In the present study,
      we investigated the effect of newly isolated phenylamine derivative N-benzyl-N
      methyldecan-1-amine (NBNMA) from garlic cloves on the inhibition of the growth
      and apoptosis of human leukemia U937 cells and its potential anticancer
      mechanism. NBNMA exhibited an antiproliferative effect in U937 cells by inducing
      cell cycle arrest at the G2/M phase and apoptotic cell death. Western blot
      analyses revealed that NBNMA decreased the expression of the regulator genes of
      G2/M phase progression, cyclin dependent kinase (Cdk) 2 and Cdc2 and elevated the
      expression of the Cdk inhibitor p21WAF1/CIP1 in a p53-independent manner. In
      addition, NBNMA activated caspase-8 and caspase-9, initiator caspases of the
      extrinsic and intrinsic pathways of apoptosis, respectively, which led to
      activation of executioner caspase-3 along with degradation of poly(ADP-ribose)
      polymerase. NBNMA-induced apoptosis was observed in parallel with an increased
      ratio of pro-apoptotic Bax and Bad/anti-apoptotic Bcl-2 and Bcl-xL, and
      inhibition of inhibitor of apoptosis protein (IAP) family members XIAP and cIAP
      1. Furthermore, NBNMA-treated cells displayed enhanced release of cytochrome c
      from the mitochondria into the cytosol concomitant with a loss of mitochondrial
      membrane potential and downregulation of Bid, suggesting that NBNMA-induced
      apoptosis occurred via the extrinsic and intrinsic apoptotic pathways with a
      possible link to Bid protein activity between the two pathways. These results
      indicate that NBNMA has promising potential to become a novel anticancer agent
      for the treatment of leukemia. We provide new insight into the mechanisms
      underlying the anticancer effect of NBNMA.

PMID- 24859826
TI  - Anti-tumor activities of Au(I) complexed with bisphosphines in HL-60 cells.
AB  - We found that Au(I) complexed with 2,3-bis(tert-butyl(methyl)phosphino)
      quinoxaline (10) was a potent anti-tumor agent (half-maximal growth inhibitory
      concentration, GI50=0.87MUM) with broad anti-tumor activity. In particular, the
      activity of complex 10 was high in tumor cell lines derived from the colon and
      ovary. Treatment with complex 10 resulted in the apoptosis of HL-60 cells. The
      ligand for the preparation of complex 10 is commercially available implying that
      complex 10 might be a good drug candidate for cancer therapy. 

PMID- 24859827
TI  - Malaria drug resistance: the impact of human movement and spatial heterogeneity.
AB  - Human habitat connectivity, movement rates, and spatial heterogeneity have
      tremendous impact on malaria transmission. In this paper, a deterministic system
      of differential equations for malaria transmission incorporating human movements
      and the development of drug resistance malaria in an [Formula: see text] patch
      system is presented. The disease-free equilibrium of the model is globally
      asymptotically stable when the associated reproduction number is less than unity.
      For a two patch case, the boundary equilibria (drug sensitive-only and drug
      resistance-only boundary equilibria) when there is no movement between the
      patches are shown to be locally asymptotically stable when they exist; the co
      existence equilibrium is locally asymptotically stable whenever the reproduction
      number for the drug sensitive malaria is greater than the reproduction number for
      the resistance malaria. Furthermore, numerical simulations of the connected two
      patch model (when there is movement between the patches) suggest that co
      existence or competitive exclusion of the two strains can occur when the
      respective reproduction numbers of the two strains exceed unity. With slow
      movement (or low migration) between the patches, the drug sensitive strain
      dominates the drug resistance strain. However, with fast movement (or high
      migration) between the patches, the drug resistance strain dominates the drug
      sensitive strain. 

PMID- 24859828
TI  - Landscape diversity influences dispersal and establishment of pest with complex
      nutritional ecology.
AB  - We studied the effects of landscape structure on species with resource
      nutritional partition between the immature and adult stages by investigating how
      food quality and spatial structure of a landscape may affect the invasion and
      colonization of the insect pest, Diabrotica speciosa. To this end, we formulated
      two bidimensional stochastic cellular automata, one for the insect immature stage
      and the other for the adult stage. The automata are coupled by adult oviposition
      and emergence. Further, each automata site has a specific culture type, which can
      affect differently the fitness attributes of immatures and adults, such as
      mortality, development and oviposition rates. We derived the mean-field
      approximation for these automata model, from which we obtained conditions for
      insect invasion. We ran numerical simulations using entomological parameters
      obtained from laboratory experiments (using bean, soybean, potato, and corn
      crops), and we compared the results of the automata with the ones given by the
      mean-field approximation. Finally, using artificially generated landscapes, we
      discussed how the structured heterogeneous landscape can affect dispersal and
      establishment of insect populations. 

PMID- 24859829
TI  - TET2 gene mutation is unfavorable prognostic factor in cytogenetically normal
      acute myeloid leukemia patients with NPM1+ and FLT3-ITD - mutations.
AB  - Cytogenetically normal acute myeloid leukemia (cn-AML) is a group of
      heterogeneous diseases. Gene mutations are increasingly used to assess the
      prognosis of cn-AML patients and guide risk-adapted treatment. In the present
      study, we analyzed the molecular genetics characteristics of 373 adult cn-AML
      patients and explored the relationship between TET2 gene mutations or different
      genetic mutation patterns and prognosis. We found that 16.1 % of patients had
      TET2 mutations, 31.6 % had FLT3 internal tandem duplications (ITDs), 6.2 % had
      FLT3 tyrosine kinase domain mutations, 2.4 % had c-KIT mutations, 37.8 % had NPM1
      mutations, 11.3 % had WT1 mutations, 5.9 % had RUNX1 mutations, 11.5 % had ASXL1
      mutations, 3.8 % had MLL-PTDs, 7.8 % had IDH1 mutations, 7.8 % had NRAS
      mutations, 12.3 % had IDH2 mutations, 1.6 % had EZH2 mutations, and 14.7 % had
      DNMT3A mutations, while none had CBL mutations. Gene mutations were detected in
      76.94 % (287/373) of all patients. In the NPM1m(+) patients, those with TET2
      mutations were associated with a shorter median overall survival (OS) as compared
      to TET2 wild-type (wt) patients (9.9 vs. 27.0 months, respectively; P = 0.023);
      Interestingly, the TET2 mutation was identified as an unfavorable prognostic
      factor and was closely associated with a shorter median OS as compared to TET2-wt
      (9.5 vs. 32.2 months, respectively; P = 0.013) in the NPM1m(+)/FLT3-ITDm(-)
      patient group. Thus, identification of TET2 combined with classic NPM1 and FLT3
      ITD mutations allowed us to stratify cn-AML into distinct subtypes.

PMID- 24859830
TI  - No major role for the transcription factor NF-kappaB in bone marrow function
      during peritonitis in the mouse.
AB  - Nuclear factor-kappa B (NF-kappaB) is a multipotent transcription factor that
      plays a pivotal role in immune reactions, inflammation, and possibly
      hematopoiesis as well. Mobilization of neutrophilic granulocytes during
      inflammation is a highly regulated process, but one that is incompletely
      understood. We studied the in vivo activity of NF-kappaB in mouse organs and
      cells, with a focus on bone marrow, during acute inflammation. NF-kappaB activity
      was studied in transgenic mice expressing a luciferase reporter expressed in a NF
      kappaB activation-dependent fashion. Acute peritoneal inflammation was induced by
      lipopolysaccharide (LPS), the casein digest bacto-tryptone, or the insoluble
      polysaccharide zymosan. Organs were removed and blood, bone marrow, and
      peritoneal cells were separated using density gradient centrifugation. NF-kappaB
      activity in organ homogenates and cell lysates was quantified. These three
      inflammatory agents increased NF-kappaB activity to a variable extent within the
      inflamed peritoneal cavity, liver, and spleen, with LPS being the strongest
      stimulus. LPS, but not bacto-tryptone or zymosan, activated NF-kappaB in lung and
      bone marrow, the latter activity mainly observed in density fractions rich in
      immature bone marrow cells. NF-kappaB activation was prominent at 6 h after
      induction of peritonitis, fading at 24 h, as expected for an acute phase
      phenomenon. From this proof-of-principle study with luciferase reporter mice
      dependent on NF-kappaB activation, we suggest that, in steady-state mice,
      mobilization of bone marrow granulocytes to an inflammatory site can occur
      without discernible activation of NF-kappaB in bone marrow.

PMID- 24859831
TI  - Early clinical effects of the Dynesys system plus transfacet decompression
      through the Wiltse approach for the treatment of lumbar degenerative diseases.
AB  - BACKGROUND: This study investigated early clinical effects of Dynesys system plus
      transfacet decompression through the Wiltse approach in treating lumbar
      degenerative diseases. MATERIAL AND METHODS: 37 patients with lumbar degenerative
      disease were treated with the Dynesys system plus transfacet decompression
      through the Wiltse approach. RESULTS: Results showed that all patients healed
      from surgery without severe complications. The average follow-up time was 20
      months (9-36 months). Visual Analogue Scale and Oswestry Disability Index scores
      decreased significantly after surgery and at the final follow-up. There was a
      significant difference in the height of the intervertebral space and
      intervertebral range of motion (ROM) at the stabilized segment, but no
      significant changes were seen at the adjacent segments. X-ray scans showed no
      instability, internal fixation loosening, breakage, or distortion in the follow
      up. CONCLUSIONS: The Dynesys system plus transfacet decompression through the
      Wiltse approach is a therapeutic option for mild lumbar degenerative disease.
      This method can retain the structure of the lumbar posterior complex and the
      motion of the fixed segment, reduce the incidence of low back pain, and
      decompress the nerve root.

PMID- 24859832
TI  - Large-scale uniform Au nanodisk arrays fabricated via x-ray interference
      lithography for reproducible and sensitive SERS substrate.
AB  - Large-scale Au nanodisk arrays on Si substrate are successfully fabricated via x
      ray interference lithography and followed by electron-beam vapor deposition. The
      Au nanodisk arrays exhibit a significant, uniform, and reproducible surface
      enhancement on Raman scattering signal, which enables the detection of R6G as low
      as 10(-8) M with an enhancement factor of 10(6). Importantly, the Au nanodisk
      arrays SERS-active substrates with uniformly high sensitivity also have high
      reproducibility and stability. The diameters of the nanodisks and the inter-disk
      distance can be simply optimized to obtain high enhancement in Raman signal by
      varying exposure time and development time in XIL process. The electric fields of
      the Au nanodisks with various diameters and inter-disk distance simulated by the
      finite difference time domain (FDTD) techniques further confirm that the Raman
      signal enhancement of Au nanodisks is determined by the diameters of nanodisks
      and the inter-disk distance of nanodisks. The Au/Ag double-layer bimetal nanodisk
      arrays are also fabricated which show a significant increase in the Raman signal
      enhancement than that of the Au nanodisk arrays. XIL nanofabrication appears to
      be a feasible approach to prepare uniform and reproducible SERS-active substrates
      with high sensitivity for practical SERS applications. 

PMID- 24859833
TI  - Polymorphisms in ERCC1 gene could predict clinical outcome of platinum-based
      chemotherapy for non-small cell lung cancer patients.
AB  - We analyzed the role of three common single-nucleotide polymorphisms (SNPs) of
      ERCC1 in predicting the tumor responses and the survival of non-small cell lung
      cancer (NSCLC) patients who received platinum-based chemotherapy. One hundred
      ninety-two patients who were identified as stage IV or IIIB/A NSCLC were
      collected between January 2008 and December 2009. ERCC1 rs11615, rs3212986, and
      rs2298881 were selected and genotyped by MassARRAY(r) Analyzer 4 system. One
      hundred three (53.65 %) patients showed a CR and PR to chemotherapy, and 81
      (42.19 %) patients died from NSCLC with the median OS of 35.82 +/- 15.19 months.
      Multivariate regression analysis showed that rs11615 TT genotype and T allele
      were associated with optimal response to chemotherapy, and rs3212986 AA and A
      allele were correlated with better response to chemotherapy. Cox regression
      showed that patients carrying the rs11615 TT genotype and T allele and the
      rs3212986 AA genotype and A allele were significantly associated with higher risk
      of death from NSCLC. In conclusion, ERCC1 rs11615 and rs3212986 polymorphism were
      associated with a poor response to chemotherapy and shorter survival time of
      advanced NSCLC. ERCC1 rs11615 and rs3212986 polymorphisms may be helpful for
      designing individualized cancer treatment for NSCLC patients.

PMID- 24859834
TI  - Activating transcription factor 3 promotes colon cancer metastasis.
AB  - Colorectal cancer is one of the commonest of solid malignancy in the world.
      Activating transcription factor 3 (ATF3), a homolog of the mouse TI-241 and rat
      LFR-1, is a stress responsive gene that has been widely indicated in different
      malignancies. However, the role of ATF3 in colon cancer is paradoxical with both
      a suggested pro- and anti-tumorigenic role. The objective of the current study
      was to investigate the role of ATF3 in colon cancer metastasis using HT29 and
      CaCO2 colon cancer cell lines. Expression of ATF3 was initially evaluated in five
      pairs of colon cancer and matched noncancerous colon tissues. The role of ATF3 in
      promoting in vitro migration and invasion were evaluated by siRNA-mediated
      knockdown and adenovirus-mediated overexpression of ATF3. In addition, the role
      of ATF3 in promoting in vivo tumor growth and hepatic metastasis was investigated
      by shRNA-mediated knockdown of ATF3. Expression of ATF3 was more in the colon
      cancer tissues as compared with the pooled noncancerous control colon tissue. Our
      results showed that in both HT29 and CaCO2 cells, ATF3 promoted in vitro motility
      and invasion. Furthermore, knockdown of ATF3 attenuated subcutaneous tumor growth
      and CD31(+) neovasculature in xenograft assays with HT29 and CaCO2 cells and
      inhibited hepatic metastasis. Cumulatively, our results unequivocally show that
      ATF3 promotes colon cancer metastasis.

PMID- 24859835
TI  - The influence of ESR1 rs9340799 and ESR2 rs1256049 polymorphisms on prostate
      cancer risk.
AB  - Estrogen receptor 1 (ESR1) and estrogen receptor 2 (ESR2) may play a role in the
      development of prostate cancer. Many studies focused on ESR1 rs9340799 and ESR2
      rs1256049 polymorphisms to explore associations with prostate cancer risk. These
      studies showed inconsistent and conflicting results. The aim of this meta
      analysis was to investigate the pooled association of ESR1 rs9340799 and ESR2
      rs1256049 polymorphisms with prostate cancer risk. A systematic literature search
      was conducted to identify related studies (up to February 2014) in several online
      databases including PubMed, Google Scholar, CNKI and Wanfang online libraries. A
      total of 16 eligible articles were enrolled in this updated meta-analysis. The
      result suggested that ESR1 rs9340799 polymorphism was significantly associated
      with prostate cancer in overall populations (GG+GA vs. AA: P = 0.002; G vs. A: P
      = 0.004), Caucasians (GG+GA vs. AA: P = 0.008; G vs. A: P = 0.016) and Africans
      (GG+GA vs. AA: P = 0.005; G vs. A: P = 0.006), but not in Asians (GG+GA vs. AA: P
      = 0.462; G vs. A: P = 0.665). The result also showed that there was a significant
      association between ESR2 rs1256049 polymorphism and prostate cancer in Caucasians
      (AA+AG vs. GG: P = 0.016; A vs. G: P = 0.005), but no association in overall
      populations (AA+AG vs. GG: P = 0.826; A vs. G: P = 0.478), Asians (AA+AG vs. GG:
      P = 0.177; A vs. G: P = 0.703) and Africans (AA+AG vs. GG: P = 0.847; A vs. G: P
      = 0.707). The cumulative meta-analysis and sensitivity analysis showed the
      results were robust. In conclusion, this meta-analysis indicated that ESR1
      rs9340799 polymorphism was associated with prostate cancer risk in overall
      populations, Caucasians and Africans, while ESR2 rs1256049 polymorphism was
      associated with prostate cancer risk in Caucasians. However, the biological
      mechanisms need to be further investigated.

PMID- 24859836
TI  - Functional IRGM polymorphism is associated with language impairment in glioma and
      upregulates cytokine expressions.
AB  - Immunity-related GTPase family M protein (IRGM) is a human protein recently
      highlighted for its contribution to autophagy upon infections. Evidences have
      shown that IRGM may also play critical roles in the pathogenesis of cancer.
      However, correlation between IRGM and glioma remains unclear. In the current
      study, we investigated two IRGM genetic polymorphisms, rs10065172C/T and
      rs13361189T/C, in glioma and their effects on cytokine expression. Data showed
      that prevalences of rs13361189TC genotype were significantly increased in glioma
      patients than in healthy controls (odds ratio (OR) = 1.53, 95 % confidence
      interval (CI) 1.05-2.24, P = 0.028), and frequency of polymorphic rs13361189CC
      genotype was further elevated (OR = 2.43, 95 % CI 1.43-4.14, P = 0.001).
      Interestingly, rs13361189TC and CC genotypes revealed a strong association with
      language impairment in glioma patients (OR = 2.16, P = 0.023; OR = 3.71, P =
      0.001, respectively). When analyzing these two polymorphisms with related
      cytokine expression, we observed that subjects carrying rs13361189CC genotype had
      higher serum level of interferon-gamma (IFN-gamma) than those with wild-type TT
      genotype (P < 0.01). In addition, subjects with rs13361189TC and CC genotypes
      presented elevated serum level of interleukin 4 (IL-4) than those with TT
      genotype. These data indicate a potential role of IRGM in the development of
      glioma probably by affecting IFN-gamma and IL-4.

PMID- 24859837
TI  - MiR-335 functions as a tumor suppressor in pancreatic cancer by targeting OCT4.
AB  - Octamer-binding transcription factor 4 (OCT4) was closely related to pancreatic
      cancer progression, but its regulation in pancreatic cancer by microRNA (miRNA)
      is not fully clear. OCT4-positive and OCT4-negative pancreatic cells were
      isolated by flow cytometry, and it was found that OCT4-positive cells are
      enriched in transplanted pancreatic cancer cells compared with the primary ones
      and showed increasing proliferation and sphere formation. The data of miRNA array
      assay showed that miR-335 in OCT4-positive pancreatic cancer cells was lower than
      that in the negative ones. The results were confirmed in pancreatic cancer tissue
      and cell lines. Through expression analysis, it was found that miR-335 was
      underexpressed in OCT4(+) pancreatic cancer cells purified from primary tumors.
      Enforced expression of miR-335 in OCT4(+) pancreatic cancer cells inhibited
      clonogenic expansion and tumor development. miR-335 re-expression in OCT4(+)
      pancreatic cancer cells was blocked. Systemically delivered miR-335 inhibited
      pancreatic cancer metastasis and extended animal survival. Of significance, OCT4
      was identified and validated as a direct and functional target of miR-335. Taken
      together, our results provide evidence that miR-335 might inhibit progression and
      stem cell properties of pancreatic cancer targeting OCT4. 

PMID- 24859838
TI  - Induction of apoptosis in human peritoneal mesothelial cells by gastric cancer
      cell supernatant promotes peritoneal carcinomatosis.
AB  - This study was carried out to evaluate the effects of gastric cancer cell
      supernatant on human peritoneal mesothelial cell viability and apoptosis and to
      investigate the mechanism of action of gastric cancer in a mesothelial cell line
      (HMrSV5). Cell viability was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyl tetrazoliumbromide (MTT) assay. Mesothelial cells treated with gastric
      cancer cell supernatant were stained with acridine orange/ethidium bromide and
      subjected to fluorescence microscopy. C57BL/6 mice were used to establish a
      cancer invasion model. Morphological changes and exfoliation occurred, and naked
      areas appeared in both cultured mesothelial cells and the parietal peritoneum
      after treatment with gastric cancer cell supernatant. Cell supernatant from
      gastric cancer cells induced apoptosis of mesothelial cells in a time-dependent
      manner. Obvious morphological changes of cell apoptosis were detected, such as
      condensation of chromatin, nuclear fragmentations, and apoptotic ladders. These
      findings demonstrate that gastric cancer cells induce apoptosis of human
      peritoneal mesothelial cells through supernatants in early peritoneal metastasis.

PMID- 24859839
TI  - Selective attention and recognition: effects of congruency on episodic learning.
AB  - Recent research on cognitive control has focused on the learning consequences of
      high selective attention demands in selective attention tasks (e.g., Botvinick,
      Cognit Affect Behav Neurosci 7(4):356-366, 2007; Verguts and Notebaert, Psychol
      Rev 115(2):518-525, 2008). The current study extends these ideas by examining the
      influence of selective attention demands on remembering. In Experiment 1,
      participants read aloud the red word in a pair of red and green spatially
      interleaved words. Half of the items were congruent (the interleaved words had
      the same identity), and the other half were incongruent (the interleaved words
      had different identities). Following the naming phase, participants completed a
      surprise recognition memory test. In this test phase, recognition memory was
      better for incongruent than for congruent items. In Experiment 2, context was
      only partially reinstated at test, and again recognition memory was better for
      incongruent than for congruent items. In Experiment 3, all of the items contained
      two different words, but in one condition the words were presented close together
      and interleaved, while in the other condition the two words were spatially
      separated. Recognition memory was better for the interleaved than for the
      separated items. This result rules out an interpretation of the congruency
      effects on recognition in Experiments 1 and 2 that hinges on stronger relational
      encoding for items that have two different words. Together, the results support
      the view that selective attention demands for incongruent items lead to encoding
      that improves recognition. 

PMID- 24859840
TI  - Cross-category adaptation: exposure to faces produces gender aftereffects in body
      perception.
AB  - Prolonged exposure to a stimulus results in a subsequent perceptual bias. This
      perceptual adaptation aftereffect occurs not only for simple stimulus features
      but also for high-level stimulus properties (e.g., faces' gender, identity and
      emotional expressions). Recent studies on aftereffects demonstrate that
      adaptation to human bodies can modulate face perception because these stimuli
      share common properties. Those findings suggest that the aftereffect is not
      related to the physical property of the stimulus but to the great number of
      semantic attributes shared by the adapter and the test. Here, we report a novel
      cross-category adaptation paradigm with both silhouette face profiles (Experiment
      1.1) and frontal view faces (Experiment 2) as adapters, testing the aftereffects
      when viewing an androgynous test body. The results indicate that adaptation to
      both silhouette face profiles and frontal view faces produces gender aftereffects
      (e.g., after visual exposure to a female face, the androgynous body appears as
      more male and vice versa). These findings confirm that high-level perceptual
      aftereffects can occur between cross-categorical stimuli that share common
      properties. 

PMID- 24859841
TI  - "Equivocal" high-risk HPV DNA tests performed on ThinPrep specimens after ASC-US
      diagnoses are associated with an increased incidence of CIN3: a
      cytologic/histologic review of 315 cases.
AB  - OBJECTIVE: The Hybrid Capture II high-risk HPV test (HC II hrHPVT) improves early
      detection of cervical neoplasia in Pap tests. However, weakly positive HC II
      results may be reported as indeterminate or "equivocal," for which there is
      little clinical guidance. This study is designed to evaluate the clinical outcome
      of equivocal HC II hrHPVTs and concurrent atypical squamous cells of undetermined
      significance (ASC-US) on ThinPrep Pap specimens through correlation with 2-year
      follow-up cervical biopsies. MATERIALS AND METHODS: Over a 5-year period,
      ThinPrep Pap tests diagnosed as ASC-US were grouped according to their hrHPVT
      results (i.e., positive, negative, or equivocal) and correlated with histologic
      follow-up. All equivocal and representative positive and negative hrHPVTs were
      included. Biopsies showing high-grade dysplasia were reviewed by two
      pathologists. RESULTS: Of 9,012 ASCUS Pap tests, 945 had corresponding hrHPVTs
      and follow-up cervical biopsies. High-grade squamous intraepithelial lesion (HSIL
      cervical intraepithelial neoplasia grades 2/3, CIN2/3) was identified in 20.3%
      (14/69) of biopsies after equivocal hrHPVTs (CIN2-5.8%, CIN3-14.5% (p=.0261);
      16.7% (25/150) after positive hrHPVT (CIN2-12%, CIN3-4.7%); and 5.4% (5/93) of
      biopsies after negative hrHPVT (CIN2-4.3%, CIN3-1.1%). CONCLUSION: ASC-US in
      association with equivocal and positive HC II results respectively shows similar
      incidences of CIN2/3 on 2-year follow-up cervical biopsy. Additionally, a
      significant proportion of CIN3 biopsies are in the equivocal HC II cohort. As
      clinical decision making would be impacted by this finding, laboratories should
      consider evaluating the clinical performance of their HC II assay via correlation
      with subsequent cervical biopsies.

PMID- 24859842
TI  - Success rate of cold coagulation for the treatment of cervical intraepithelial
      neoplasia: a retrospective analysis of a series of cases.
AB  - OBJECTIVE: To establish the cure rate at 1 year of patients who have undergone
      cold coagulation for the treatment of cervical intraepithelial neoplasia (CIN).
      DESIGN: Retrospective review of data for all patients at Shrewsbury and Telford
      NHS Trust who had undergone cold coagulation as part of their treatment for CIN
      between 2001 and 2011. Follow-up data up to December 2012 were analyzed. SETTING:
      Colposcopy Department, Shrewsbury and Telford NHS Trust, United Kingdom.
      POPULATION: Women undergoing cold coagulation for the treatment of CIN between
      2001 and 2011, with cytologic follow-up until December 2012. METHODS: Patients
      were identified using a local colposcopy database. Data were obtained via the
      local histopathology reporting systems. Statistical analyses were performed using
      Stata/IC 10.1 software. MAIN OUTCOME MEASURES: Posttreatment cytology and whether
      subsequent treatment was required, with histology results. RESULTS: Data on 557
      patients were collected and analyzed. Pre-cold coagulation treatment histologic
      findings were CIN 1 in 156 patients (28.01%), CIN 2 in 260 patients (46.68%), and
      CIN 3 in 141 patients (25.31%). The median length of time between cold
      coagulation treatment and first follow-up smear, used to calculate cure rates at
      around 1 year, was 406 days (interquartile range 123 days, range 169-3,116 days).
      The cure rate after cold coagulation was 95.7% at around 1 year. CONCLUSIONS:
      Cold coagulation has a cure rate comparable to that of excisional treatments such
      as large loop excision of the transformation zone and should be considered more
      widely in patients undergoing primary treatment for CIN, where there is no
      suspicion of invasive disease on history, examination and cytologic results.

PMID- 24859843
TI  - Remission of vulvar pain among women with primary vulvodynia.
AB  - OBJECTIVE: To determine whether rates of remission differed among women with
      primary versus secondary vulvodynia. METHODS: Using a community-based
      observational study based in Minneapolis/St. Paul, 138 clinically confirmed cases
      of vulvodynia between 18 and 40 years old were classified as primary (vulvar pain
      starting at the time of sexual debut or first tampon insertion) or secondary
      (vulvar pain starting after a period of pain-free intercourse) and queried
      regarding their pain history to determine whether they had ever experienced any
      vulvar pain-free time (remission) or pain-free time lasting 3 months or longer.
      RESULTS: Remission prevalence was 26% (9/34) for women in the shortest quartile
      of duration of vulvar pain (<3.8 y) and 38% (13/34) for the longest quartile of
      duration (>=13 y). After adjusting for vulvar pain duration, generalized
      vestibular pain, medical treatment, body mass index, and history of pregnancy,
      women who had primary vulvodynia were 43% less likely to report remission (95% CI
      = 0.33-0.99) than women with later onset (secondary cases). The association was
      strengthened when restricting to only remissions lasting 3 months or longer
      (adjusted risk ratio = 0.43, 95% CI = 0.22-0.84). Generalized vestibulodynia and
      obesity also reduced the likelihood of remission. CONCLUSIONS: Our study
      underscores the heterogeneity of vulvodynia and provides evidence that primary
      vulvodynia may have a less wavering course and, as such, a potentially different
      underlying mechanism than that of secondary vulvodynia.

PMID- 24859844
TI  - Squamous intraepithelial lesions in cervical tissue samples of limited adequacy
      and insufficient for grading as low or high grade: outcome, clinico-pathological
      correlates, and predictive role of p16INK4a and Ki67 biomarker staining.
AB  - OBJECTIVE: Cervical tissue samples of limited adequacy but with pathological
      features of squamous intraepithelial lesions (SIL) may not be gradable and result
      in a diagnosis of ungraded SIL (SILQ). SILQ outcome, clinico-pathological
      correlates, and the predictive role of biomarker staining are unknown. MATERIALS
      AND METHODS: Among 17,551 colposcopy attendees, 478 (2.7%) had SILQ. Glass slides
      of 472 were reviewed. Positive [high SIL (HSIL), adenocarcinoma in situ (AIS), or
      carcinoma] and negative [negative for intraepithelial lesion or malignancy (NILM)
      or low SIL (LSIL)] outcomes were based on the worst pathology in 24 months of
      follow-up. p16 and Ki67 immunohistochemistry of 80 random SILQ and 149 controls
      (44 NILM, 15 LSIL, 75 HSIL, and 15 AIS) was scored as unsatisfactory, positive,
      or negative. Biomarker and outcome status were correlated, and sensitivity,
      specificity positive predictive value (PPV), and negative predictive value (NPV)
      were calculated. RESULTS: Of the total cases, 332 (1.9%) were reviewed as SILQ,
      and follow-up for 329 was positive in 134 (41%). Atypical glandular cells, AIS,
      atypical squamous cells (cannot exclude HSIL), HSIL referral Pap test (70% vs.
      47%, p < .001), and HSIL colposcopic impression (33% vs. 19%, p < .001) were more
      frequent among positive compared with negative outcomes. Best SILQ sensitivity
      (89%) and NPV (77%) occurred with combined biomarkers, and best specificity (52%)
      and PPV (58%) occurred with Ki67. All 4 performance metrics among the controls
      were high. CONCLUSIONS: The 2% frequency and 41% positive outcome highlight the
      clinical importance of SILQ. The referral Pap test and colposcopic impression
      could prioritize follow-up colposcopy for some SILQ, and negative staining with
      both biomarkers could eliminate further colposcopy in others.

PMID- 24859845
TI  - PUMA regulates germ cell loss and primordial follicle endowment in mice.
AB  - The number of primordial follicles initially established within the ovary is
      influenced by the extent of germ cell death during foetal ovarian development,
      but the mechanisms that mediate this death have not been fully uncovered. In this
      study, we identified BBC3 (PUMA) (p53 upregulated modulator of apoptosis, also
      known as BCL2-binding component 3), a pro-apoptotic BH3-only protein belonging to
      the BCL2 family, as a critical determinant of the number of germ cells during
      ovarian development. Targeted disruption of the Bbc3 gene revealed a significant
      increase in the number of germ cells as early as embryonic day 13.5. The number
      of germ cells remained elevated in Bbc3(-/-) female mice compared with WT female
      mice throughout the remainder of embryonic and early postnatal life, resulting in
      a 1.9-fold increase in the number of primordial follicles in the ovary on
      postnatal day 10. The increase in the number of germ cells observed in the
      ovaries of Bbc3(-/-) mice could not be attributed to the altered proliferative
      activity of germ cells within the ovaries. Furthermore, BBC3 was found to be not
      required for the massive germ cell loss that occurs during germ cell nest
      breakdown. Our data indicate that BBC3 is a critical regulator of germ cell death
      that acts during the migratory phase of oogenesis or very soon after the arrival
      of germ cells in the gonad and that BBC3-mediated cell death limits the number of
      primordial follicles established in the initial ovarian reserve. 

PMID- 24859846
TI  - A modular and programmable development platform for capsule endoscopy system.
AB  - The state-of-the-art capsule endoscopy (CE) technology offers painless
      examination for the patients and the ability to examine the interior of the
      gastrointestinal tract by a noninvasive procedure for the gastroenterologists. In
      this work, a modular and flexible CE development system platform consisting of a
      miniature field programmable gate array (FPGA) based electronic capsule, a
      microcontroller based portable data recorder unit and computer software is
      designed and developed. Due to the flexible and reprogrammable nature of the
      system, various image processing and compression algorithms can be tested in the
      design without requiring any hardware change. The designed capsule prototype
      supports various imaging modes including white light imaging (WLI) and narrow
      band imaging (NBI), and communicates with the data recorder in full duplex
      fashion, which enables configuring the image size and imaging mode in real time
      during examination. A low complexity image compressor based on a novel color
      space is implemented inside the capsule to reduce the amount of RF transmission
      data. The data recorder contains graphical LCD for real time image viewing and SD
      cards for storing image data. Data can be uploaded to a computer or Smartphone by
      SD card, USB interface or by wireless Bluetooth link. Computer software is
      developed that decompresses and reconstructs images. The fabricated capsule PCBs
      have a diameter of 16 mm. An ex-vivo animal testing has also been conducted to
      validate the results. 

PMID- 24859847
TI  - Cultivation and identification of rat bone marrow-derived mesenchymal stem cells.
AB  - Bone marrow-derived mesenchymal stem cells (BMSCs) have the potential to form a
      variety of mesenchymal tissue types, which are a source of cells for bone tissue
      engineering applications. The present study attempted to establish an effective
      and convenient method for culturing BMSCs. Total bone marrow cells, which were
      harvested from rat femurs, were cultured and BMSCs were selected and expanded
      through passaging in vitro. Furthermore, the biological properties of BMSCs were
      investigated, specific surface antigen expression was assessed using flow
      cytometry and the multipotent differentiation potential characteristics were
      demonstrated using standard in vitro conditions. Monoptychial heterogeneous cells
      were obtained. A total of 98.4% of cells at passage 3 expressed cluster of
      differentiation (CD)29 and CD90, but not CD45. The cells were able to
      differentiate into osteogenic and adipogenic cells. In conclusion, BMSCs that are
      isolated from the rat bone marrow and exhibit the identified characteristics may
      be used as seed cells in bone tissue engineering. 

PMID- 24859848
TI  - Oridonin inhibits the proliferation of human osteosarcoma cells by suppressing
      Wnt/beta-catenin signaling.
AB  - It has been reported that oridonin (ORI) can inhibit proliferation and induce
      apoptosis in various types of cancer cell lines. However, the exact mechanism for
      this function remains unclear. In this study, we investigated the proliferation
      inhibitory effect of ORI on human osteosarcoma (OS) 143B cells and dissected the
      possible molecular mechanism(s) underlying this effect. We demonstrated that ORI
      can inhibit proliferation, induce apoptosis and arrest the cell cycle in 143B
      cells. Using luciferase reporter assay, we found that the Wnt/beta-catenin
      signaling was inhibited in 143B cells by ORI. Accordingly, the total protein
      levels and nuclear translocation of beta-catenin were reduced by ORI treatment.
      ORI increased glycogen synthase kinase 3beta (GSK3beta) activity and upregulated
      Dickkopf-1 (Dkk-1) expression. We found that Dkk-1 overexpression or beta-catenin
      knockdown can potentiate the proliferation inhibitory effect of ORI in 143B
      cells, while beta-catenin overexpression attenuated this effect. Using the
      xenograft tumor model of human OS, we demonstrated that ORI effectively inhibited
      the growth of tumors. Histological examination showed that ORI inhibited cancer
      cell proliferation, decreased the expression of PNCA and beta-catenin. Our
      findings suggest that ORI can inhibit 143B OS cell proliferation by
      downregulating Wnt/beta-catenin signal transduction, which may be mediated by
      upregulating the Dkk-1 expression and/or enhancing the function of GSK3beta.
      Therefore, ORI can be potentially used as an effective adjuvant agent for the
      clinical management of OS.

PMID- 24859849
TI  - Birth intervention and non-maternal infant-handling during parturition in a
      nonhuman primate.
AB  - Direct intervention in infant delivery by non-parturient individuals is a rare
      phenomenon in nonhuman primates. In contrast, birth assistance by other
      individuals, or the practice of midwifery, is universal among human societies and
      generally believed to be a behavior unique to our species. It has been proposed
      that the enlarged head of the human fetus and the relatively narrow birth canal
      constrained by bipedalism has made human parturition more difficult than in
      nonhuman primates, and these anatomic challenges have led to the rotation of the
      fetus in the birth canal and an occiput anterior (i.e., backward-facing)
      orientation of emergence. These characteristics have hindered the mother's
      ability to self-assist the delivery of the infant, therefore necessitating
      assistance by other individuals or midwives for successful birth. Here we report
      the first high-definition video recordings of birth intervention behavior in a
      wild nonhuman primate, the white-headed langur (Trachypithecus leucocephalus). We
      observed that while a primiparous female gave birth to an infant in an occiput
      posterior (i.e., forward-facing) orientation, a multiparous female intervened in
      the delivery by manually pulling the infant out of the birth canal and cared for
      it in the following hours. Our finding shows extensive social interactions
      throughout parturition, and presents an unequivocal case of non-maternal
      intervention with infant birth in a nonhuman primate. 

PMID- 24859850
TI  - Ultra-low-dose computed tomographic angiography with model-based iterative
      reconstruction compared with standard-dose imaging after endovascular aneurysm
      repair: a prospective pilot study.
AB  - PURPOSE: An ultra-low-dose radiation protocol reconstructed with model-based
      iterative reconstruction was compared with our standard-dose protocol. METHODS:
      This prospective study evaluated 20 men undergoing surveillance-enhanced computed
      tomography after endovascular aneurysm repair. All patients underwent standard
      dose and ultra-low-dose venous phase imaging; images were compared after
      reconstruction with filtered back projection, adaptive statistical iterative
      reconstruction, and model-based iterative reconstruction. Objective measures of
      aortic contrast attenuation and image noise were averaged. Images were
      subjectively assessed (1 = worst, 5 = best) for diagnostic confidence, image
      noise, and vessel sharpness. Aneurysm sac diameter and endoleak detection were
      compared. RESULTS: Quantitative image noise was 26% less with ultra-low-dose
      model-based iterative reconstruction than with standard-dose adaptive statistical
      iterative reconstruction and 58% less than with ultra-low-dose adaptive
      statistical iterative reconstruction. Average subjective noise scores were not
      different between ultra-low-dose model-based iterative reconstruction and
      standard-dose adaptive statistical iterative reconstruction (3.8 vs. 4.0, P =
      .25). Subjective scores for diagnostic confidence were better with standard-dose
      adaptive statistical iterative reconstruction than with ultra-low-dose model
      based iterative reconstruction (4.4 vs. 4.0, P = .002). Vessel sharpness was
      decreased with ultra-low-dose model-based iterative reconstruction compared with
      standard-dose adaptive statistical iterative reconstruction (3.3 vs. 4.1, P <
      .0001). Ultra-low-dose model-based iterative reconstruction and standard-dose
      adaptive statistical iterative reconstruction aneurysm sac diameters were not
      significantly different (4.9 vs. 4.9 cm); concordance for the presence of
      endoleak was 100% (P < .001). CONCLUSION: Compared with a standard-dose
      technique, an ultra-low-dose model-based iterative reconstruction protocol
      provides comparable image quality and diagnostic assessment at a 73% lower
      radiation dose.

PMID- 24859852
TI  - Accumulation and speciation of vanadium in Lycium seedling.
AB  - Lycium seedling was subjected to varying doses of V for 40-45 days to examine the
      effects on uptake, accumulation, and speciation of V in Lycium seedling by
      differential centrifugation and enzymolysis. V concentrations in Lycium seedling
      organs were in sequence as follows: root>leaf>stem. V uptake into stem and leaf
      were primarily combined with acid-soluble polar compounds, polysaccharide, and
      immobile materials on the cell walls. There were different speciations of V in
      root with different V stress levels. Enzymolysis results suggest that about 60%
      of the V in Lycium seedling root was combined with pectin and cellulose. It is
      the antidotal effect of pectin and cellulose in the cell wall that reduced the V
      damage to Lycium seedling.

PMID- 24859851
TI  - Dopaminergic modulation of cortical plasticity in Alzheimer's disease patients.
AB  - In animal models of Alzheimer's disease (AD), mechanisms of cortical plasticity
      such as long-term potentiation (LTP) and long-term depression (LTD) are impaired.
      In AD patients, LTP-like cortical plasticity is abolished, whereas LTD seems to
      be preserved. Dopaminergic transmission has been hypothesized as a new player in
      ruling mechanisms of cortical plasticity in AD. We aimed at investigating whether
      administration of the dopamine agonist rotigotine (RTG) could modulate cortical
      plasticity in AD patients, as measured by theta burst stimulation (TBS) protocols
      of repetitive transcranial stimulation applied over the primary motor cortex.
      Thirty mild AD patients were tested in three different groups before and after 4
      weeks of treatment with RTG, rivastigmine (RVT), or placebo (PLC). Each patient
      was evaluated for plasticity induction of LTP/LTD-like effects using respectively
      intermittent TBS (iTBS) or continuous TBS protocols. Short-latency afferent
      inhibition (SAI) protocol was performed to indirectly assess central cholinergic
      activity. A group of age-matched healthy controls was recruited for baseline
      comparisons. Results showed that at baseline, AD patients were characterized by
      impaired LTP-like cortical plasticity, as assessed by iTBS. These reduced levels
      of LTP-like cortical plasticity were increased and normalized after RTG
      administration. No effect was induced by RVT or PLC on LTP. LTD-like cortical
      plasticity was not modulated in any condition. Cholinergic activity was increased
      by both RTG and RVT. Our findings reveal that dopamine agonists may restore the
      altered mechanisms of LTP-like cortical plasticity in AD patients, thus providing
      novel implications for therapies based on dopaminergic stimulation. 

PMID- 24859853
TI  - Testing the genotoxicity, cytotoxicity, and oxidative stress of cadmium and
      nickel and their additive effect in male mice.
AB  - The present study was aimed to investigate the ability of cadmium (Cd) and nickel
      (Ni) to induce genotoxicity, cytotoxicity, and oxidative stress in bone marrow
      cells of male mice. Aneuploidy and chromosomal aberrations (CA) showed that Cd is
      a stronger mutagen than Ni. Cd and Ni increased significantly the incidences of
      micronucleated polychromatic erythrocytes (PCEs). Also, the ratio of
      polychromatic erythrocytes to normochromatic erythrocytes (PCE/NCE) suggests that
      treatment with higher doses of the two metals increased the cytotoxicity.
      Numerical chromosomal aberrations increased hypoploidy with the treatment which
      reached two to three times of the frequency of hyperploidy. The results showed
      that both Cd and Ni are aneugenic that act on kinetochores and cause
      malsegregation of chromosomes as well as being clastogenic. Both Cd and Ni
      increased single-break aberrations and also Cd and Ni were found to induce
      significant DNA damage in mouse bone marrow cells as assessed by the comet assay.
      In addition to the cytotoxicity results, biochemical analysis in bone marrow
      revealed a dose-dependent increase of oxidative stress markers. According to the
      results obtained, genotoxicity and cytotoxicity effects of cadmium and nickel in
      vivo are dose-dependent and are associated with oxidative stress and their
      combined effect is less than their expected additive effect, and it could be
      concluded that there are no synergistic effects resulting from the combined
      application of both metals. 

PMID- 24859854
TI  - The relationship between selenium levels and breast cancer: a systematic review
      and meta-analysis.
AB  - Breast cancer is the most common cancer type. In several studies, hints have been
      provided that there is a correlation between selenium deficiency and the
      incidence of breast cancer. Findings of these published reports are, however,
      inconsistent. This study serves as a pioneering study aiming at combining the
      results of studies using a meta-analytic method. A total of 16 articles published
      between 1980 and 2012 worldwide were selected through searching PubMed, Scopus,
      and Google scholar databases, and the information were analyzed using a meta
      analytic method [random effects model]. I (2) statistics were used to examine
      heterogeneity. The information was then analyzed by STATA version 12. In this
      study, due to the non-uniform methods used to measure selenium concentrations,
      selenium levels were measured in the various subgroups in both case and control
      groups. There were significant correlations between selenium concentration and
      breast cancer [P<0.05]. Hence, the mean risk differentiating criteria were
      estimated to be 0.63 [95% confidence interval [95% CI] 0.93 to 0.32] in serum and
      toenails. Subgroup analysis showed that the value in toenails was -0.07 [95% CI 
      0.16 to 0.03] and in serum -1.04 [95% CI 1.71 to -0.38]. In studies in which
      selenium concentrations were measured in serum, a significant correlation was
      observed between selenium concentration and breast cancer. In contrast, in
      studies in which selenium concentration was measured in toenails, the correlation
      was not significant. Therefore, the selenium concentration can be used as one
      predictor for breast cancer.

PMID- 24859855
TI  - Update on treatment strategies for anaplastic glioma: a review of literature.
AB  - Anaplastic gliomas (AG) include 6-10% of all newly diagnoses of primary brain
      tumors. They have an unfavourable prognosis and, to date, there is not an
      established treatment universally recognized. Four recent randomized clinical
      trials were identified for a total of 1,170 patients (anaplastic-astrocytomas,
      anaplasticoligoastrocytoma, anaplastic-oligodendroglioma), in order to define the
      better sequence and timing of chemo-radiotherapy, Three studies compared
      radiotherapy (RT) treatment vs. radio-chemotherapy with procarbazine-lomustine
      vincristine (PCV) or temozolomide (TMZ) or dibromodulcitol and
      bichloroethylnitrosurea (DBD/BCNU) and only one compared RT vs chemotherapy (CT)
      with PCV or TMZ. Results show no significant differences in terms of PFS/OS
      between RT/CT alone or combined treatment although a trend toward an improvement
      of OS was observed after RT + CT treatment (m-OS in RT + adjuvant PCV was 42.3
      vs. 30.6 months in RT alone p=0.0003). Grade 3-4 mielotoxicity has been observed
      in almost all cases of patients treated with PCV + RT. None of four studies
      reviewed conducted a head to head comparison between PCV vs. TMZ. Only a study
      randomized patients to PCV/TMZ without however providing data in terms of PSF and
      OS between the two treatments. It found no significant differences in PFS from
      initial RT and adjuvant CT (PCV-TMZ) at progression compared to initial CT
      followed by RT at progression. The optimal treatment of AG should reasonably
      consider not only the histology as well as the molecular markers of the tumor,
      but also clinical conditions, age of patients, life expectancy, Karnofsky
      performance-status and tumor resection to achieve in future the personalization
      of care.

PMID- 24859856
TI  - Occurrence and distribution of polycyclic aromatic hydrocarbons in surface
      microlayer and subsurface seawater of Lagos Lagoon, Nigeria.
AB  - Polycyclic aromatic hydrocarbons (PAHs) in surface microlayer (SML) and
      subsurface water (SSW) of Lagos Lagoon were investigated using gas chromatography
      electron capture detector (GC-ECD) technique to ascertain their occurrence and
      spatial distribution, origin, enrichment, and carcinogenicity. Total PAH
      (SigmaPAH) concentrations ranged from 9.10 to 16.20 MUg L(-1) in the SML and 8.90
      to 13.30 MUg L(-1) in the SSW. SigmaPAH concentrations were relatively higher in
      the SML than the underlying SSW samples. The enrichment factors (EFs) of
      SigmaPAHs ranged from 0.76 to 1.74 while the EFs of the individual PAHs varied
      from 0.50 to 2.09. In general, the EFs values calculated in this study were
      consistent or slightly less than the EFs reported for similar coastal seawater
      ecosystems. A correlation between the EFs of fluoranthene and pyrene indicated a
      positive significant value (R = 0.9828, p < 0.0001, n = 6). Source analyses using
      the phenanthrene/anthracene and fluoranthene/pyrene ratios indicated the
      dominance of petrogenic-derived PAHs. Furthermore, enhanced concentrations of BaP
      (strong carcinogenicity) in SML and SSW samples, which resulted in higher EFs,
      could pose serious ecological and human health risks.

PMID- 24859857
TI  - Diversity and dynamics of the Vibrio community in well water used for drinking in
      Guinea-Bissau (West Africa).
AB  - Bacteria of the genus Vibrio are ubiquitous in aquatic environments and can be
      found either in culturable or in a viable but nonculturable (VBNC) state. The
      genus comprises many pathogenic species accountable for water and food-borne
      diseases that prove to be fatal, especially in developing countries, as in Guinea
      Bissau (West Africa), where cholera is endemic. In order to ascertain the
      abundance and structure of Vibrio spp. community in well waters that serve as the
      sole source of water for the population, quantitative polymerase chain reaction
      (qPCR), PCR-denaturant gradient gel electrophoresis (DGGE), and cloning
      approaches were used. Results suggest that Vibrio spp. were present throughout
      the year in acidic, freshwater wells with a seasonal community composition shift.
      Vibrio spp. abundance was in accordance with the abundance found in coastal
      environments. Sequences closely related to pathogenic Vibrio species were
      retrieved from well water revealing exposure of the population to such pathogens.
      pH, ammonium, and turbidity, regulated by the rain pattern, seem to be the
      variables that contributed mostly to the shaping and selection of the Vibrio spp.
      community. These results reinforce the evidence for water monitoring with culture
      independent methods and the clear need to create/recover water infrastructures
      and a proper water resources management in West African countries with similar
      environmental conditions. 

PMID- 24859858
TI  - Application of analytic hierarchy process in a waste treatment technology
      assessment in Mexico.
AB  - The high per capita generation of solid waste and the environmental problems in
      major rural communities of Ensenada, Baja California, have prompted authorities
      to seek alternatives for waste treatment. In the absence of a selection
      methodology, three technologies of waste treatment with energy recovery (an
      anaerobic digester, a downdraft gasifier, and a plasma gasifier) were evaluated,
      taking the broader social, political, economic, and environmental issues into
      considerations. Using the scientific literature as a baseline, interviews with
      experts, decision makers and the community, and waste stream studies were used to
      construct a hierarchy that was evaluated by the analytic hierarchy process. In
      terms of the criteria, judgments, and assumptions made in the model, the
      anaerobic digester was found to have the highest rating and should consequently
      be selected as the waste treatment technology for this area. The study results
      showed low sensitivity, so alternative scenarios were not considered. The
      methodology developed in this study may be useful for other governments who wish
      to assess technologies to select waste treatment. 

PMID- 24859859
TI  - Growing stock and woody biomass assessment in Asola-Bhatti Wildlife Sanctuary,
      Delhi, India.
AB  - Biomass is an important entity to understand the capacity of an ecosystem to
      sequester and accumulate carbon over time. The present study, done in
      collaboration with the Delhi Forest Department, focused on the estimation of
      growing stock and the woody biomass in the so-called lungs of Delhi--the Asola
      Bhatti Wildlife Sanctuary in northern Aravalli hills. The satellite-derived
      vegetation strata were field-inventoried using stratified random sampling
      procedure. Growing stock was calculated for the individual sample plots using
      field data and species-specific volume equations. Biomass was estimated from the
      growing stock and the specific gravity of the wood. Among the four vegetation
      types, viz. Prosopis juliflora, Anogeissus pendula, forest plantation and the
      scrub, the P. juliflora was found to be the dominant vegetation in the area,
      covering 23.43 km(2) of the total area. The study revealed that P. juliflora
      forest with moderate density had the highest (10.7 m(3)/ha) while A. pendula
      forest with moderate density had the lowest (3.6 m(3)/ha) mean volume. The mean
      woody biomass was also found to be maximum in P. juliflora forest with moderate
      density (10.3 t/ha) and lowest in A. pendula forest with moderate density (3.48
      t/ha). The total growing stock was estimated to be 20,772.95 m(3) while total
      biomass worked out to be 19,366.83 t. A strong correlation was noticed between
      the normalized difference vegetation index (NDVI) and the growing stock (R(2) =
      0.84)/biomass (R(2) = 0.88). The study demonstrated that growing stock and the
      biomass of the woody vegetation in Asola-Bhatti Wildlife Sanctuary could be
      estimated with high accuracy using optical remote sensing data.

PMID- 24859860
TI  - Dam reservoirs role in carbon dynamics requires contextual landscape
      ecohydrology.

PMID- 24859861
TI  - Spatial distribution and source identification of trace elements in topsoil from
      heavily industrialized region, Aliaga, Turkey.
AB  - Topsoil samples (n = 40) were collected from a heavily industrialized region in
      Turkey. The region includes several scrap processing iron-steel plants with
      electric arc furnaces (EAFs), a petroleum refinery, a petrochemical complex,
      steel rolling mills, a natural gas-fired power plant, ship-breaking yards and
      very dense transportation activities. The region has undergone a rapid transition
      from an agricultural region to a heavily industrialized region in the last three
      decades. Collected soil samples were analyzed for 48 trace elements using
      inductively coupled plasma-mass spectrometry (ICP-MS). The elemental distribution
      pattern in the region indicated that Nemrut area with dense iron-steel production
      activities was a hotspot for elemental pollution. In addition to crustal
      elements, concentrations of anthropogenic trace elements (i.e., Fe, Zn, Pb, Mn,
      Cu, Cd, Cr and Mo) were very high in the area influencing many parts of the
      region. Elemental compositions of fugitive sources polluting the soil (i.e.,
      paved and unpaved roads, slag piles, EAFs filter dust piles and coal piles) were
      also determined. The methods (enrichment factors [EFs] and the index of
      geoaccumulation [Igeo]) used for determination of pollution status of soil showed
      that Cr, Ag, Zn, As and Pb were the strongly contaminating elements for the
      region. Principal component analysis (PCA) clearly indicated that anthropogenic
      sources (steel production, refinery and petrochemical processes and traffic) were
      important sources in this region.

PMID- 24859862
TI  - Exploring the diversity of Acinetobacter populations in river water with genus
      specific primers and probes.
AB  - This study aimed to explore the diversity of river water Acinetobacter
      populations using culture-dependent and -independent methods. Pyrosequencing
      indicated that 1.5% of the total sequences from Qiandeng River water were
      classified as Acinetobacter. Twelve Acinetobacter strains were isolated from
      three different sampling sites of the Qiandeng River. Based on culture-dependent
      methods, A. johnsonii, A. lwoffii and A. guillouiae were the most abundantly
      represented Acinetobacter strains among the upper, middle and downstream
      populations of the river. Probing of three Acinetobacter-enriched 16S rRNA gene
      libraries with the Acinetobacter specific probe Act660F revealed 42 unique 16S
      rRNA gene sequences exhibiting a similarity of 94.9-99.9% with the known
      Acinetobacter strains. Among the uncultured Acinetobacter sequences, 50%, 58.3%
      and 68.8% of those obtained from upstream sampling site A, middle stream sampling
      site B and downstream sampling site C were phylogenetically located within Group
      I. This Group represented the most abundant strains of Acinetobacter populations
      in river water based on culture-independent methods. The results indicated that
      culture-independent methods provide more detailed information on the diversity of
      Acinetobacter populations than that based on culture-dependent methods.
      Therefore, the development of new and efficient isolation methods to identify
      uncultured Acinetobacter species is required. 

PMID- 24859864
TI  - Metagenomic analysis of bacterial communities on Dokdo Island.
AB  - Dokdo, located east of the mainland of South Korea, is a volcanic island
      designated as a natural monument of South Korea due to its ecological value.
      Dokdo is divided into Dongdo and Seodo, islands with geological differences. The
      soil bacterial communities on Dokdo (Dongdo and Seodo) were analyzed using the
      pyrosequencing method. There were 1,693 and 1,408 operational taxonomic units
      (OTU) from Dongdo and Seodo, respectively. The statistical analyses (rarefaction
      curves as well as Chao1, Shannon, and Simpson indices) showed that bacterial
      diversity was slightly higher in Dongdo than Seodo. From results of a BLASTN
      search against the EzTaxon-e database, the validated reads (obtained after
      sequence preprocessing) were almost all classified at the phylum level. From the
      phylum level down to the species level, the number of classified reads
      considerably decreased due to the absence of information concerning unculturable
      or unidentified bacteria to date. Among the 36 phyla identified, three phyla
      (Proteobacteria, Actinobacteria and Acidobacteria) accounted for around 74.64%.
      The taxonomic composition was similar at the higher ranks (family and above)
      between Dongdo and Seodo, but a little different at the genus level. There were
      also various differences in the relative abundance of taxonomic ranks between
      Dongdo and Seodo. In particular, the proportion of the genus Acidobacterium (of
      the phylum Acidobacteria) was about six times higher in Seodo than Dongdo. In
      addition, the percentage of the genus Mycobacterium (of the phylum
      Actinobacteria) was nearly three times higher in Seodo than Dongdo, and the
      proportion of the genus Gaiella was about 3.7 times higher in Dongdo than Seodo.
      Overall, through the metagenomic analysis, the number of species identified in
      Dongdo and Seodo was 1,239 and 1,055, respectively. This information on the
      numerous culturable and unculturable bacteria is expected to help in the
      screening of new species in Dokdo. 

PMID- 24859863
TI  - Flavobacterium panaciterrae sp. nov., a beta-glucosidase producing bacterium with
      ginsenoside-converting activity isolated from the soil of a ginseng field.
AB  - The GenBank/EMBL/DDBJ accession number for the 16S rRNA gene sequence of strain
      DCY69(T) is JX233806. A Gram-reaction-negative, oxidase- and catalase-positive,
      non-gliding motile strain, designated strain DCY69(T), was isolated from the soil
      of a ginseng field in the Republic of Korea. Colonies of strain DCY69(T) were
      circular, 0.5-1.5 mm diameter, yellow, and convex on an R2A agar plate after 2
      days. Phylogenetic analyses based on 16S rRNA gene sequences revealed that strain
      DCY69(T) belonged to the genus Flavobacterium with 90.5-98.3% gene sequence
      similarity. The major predominant quinone was MK-6. The major cellular fatty
      acids were iso-C15:0, iso-C17:0 3-OH, iso-C15:0 3-OH and summed feature 3
      (containing C16:1omega7c and/or C16:1omega6c). The major polar lipids were
      phosphatidylethanolamine, one unidentified aminolipid and unidentified polar
      lipids (L1, L2). The genomic DNA G+C content of strain DCY69(T) was 35.0mol%. The
      strain DCY69(T) transformed ginsenoside Rb1 into Rd and F2. Based on the
      polyphasic taxonomic data, strain DCY69(T) is considered to represent a novel
      species of the genus Flavobacterium, for which the name Flavobacterium
      panaciterrae sp. nov. is proposed. The type strain is DCY69(T)(= KCTC 32392(T) =
      JCM 19161(T)), isolated from the soil of a ginseng field in the Republic of
      Korea. 

PMID- 24859865
TI  - Whole-genome sequence comparison as a method for improving bacterial species
      definition.
AB  - We compared pairs of 1,226 bacterial strains with whole genome sequences and
      calculated their average nucleotide identity (ANI) between genomes to determine
      whether whole genome comparison can be directly used for bacterial species
      definition. We found that genome comparisons of two bacterial strains from the
      same species (SGC) have a significantly higher ANI than those of two strains from
      different species (DGC), and that the ANI between the query and the reference
      genomes can be used to determine whether two genomes come from the same species.
      Bacterial species definition based on ANI with a cut-off value of 0.92 matched
      well (81.5%) with the current bacterial species definition. The ANI value was
      shown to be consistent with the standard for traditional bacterial species
      definition, and it could be used in bacterial taxonomy for species definition. A
      new bioinformatics program (ANItools) was also provided in this study for users
      to obtain the ANI value of any two bacterial genome pairs (http://genome.bioinfo
      icdc.org/). This program can match a query strain to all bacterial genomes, and
      identify the highest ANI value of the strain at the species, genus and family
      levels respectively, providing valuable insights for species definition. 

PMID- 24859866
TI  - Identification of a Csr system in Serratia marcescens 2170.
AB  - The carbon storage regulator (Csr) global regulatory system is conserved in many
      eubacteria and coordinates the expression of various genes that facilitate
      adaptation during the major physiological growth phase. The Csr system in
      Escherichia coli comprises an RNA-binding protein, CsrA; small non-coding RNAs,
      CsrB and CsrC; and a decay factor for small RNAs, CsrD. In this study, we
      identified the Csr system in Serratia marcescens 2170. S. marcescens CsrA was 97%
      identical to E. coli CsrA. CsrB and CsrC RNAs had typical stem-loop structures,
      including a GGA motif that is the CsrA binding site. CsrD was composed of N
      terminal two times transmembrane region and HAMP-like, GGDEF, and EAL domains.
      Overexpression of S. marcescens csr genes complemented the phenotype of E. coli
      csr mutants. S. marcescens CsrD affected the decay of CsrB and CsrC RNAs in E.
      coli. These results suggest that the Csr system in S. marcescens is composed of
      an RNA-binding protein, two Csr small RNAs, and a decay factor for Csr small
      RNAs.

PMID- 24859867
TI  - Scarless gene deletion using mazF as a new counter-selection marker and an
      improved deletion cassette assembly method in Saccharomyces cerevisiae.

PMID- 24859868
TI  - Effects of physical activity on melatonin levels in previously sedentary men and
      women.
AB  - BACKGROUND: The inverse association between physical activity and cancer risk may
      be mediated by higher melatonin levels. However, few studies have examined the
      effect of increased physical activity on melatonin levels. METHODS: The parent
      study was a randomized controlled trial that randomized 51 men and 49 women to a
      12-month moderate-to-vigorous aerobic exercise intervention ("exercisers") and 51
      men and 51 women to a stretching control ("controls"). Participants were of ages
      40 to 75 years, and previously sedentary. Levels of the principal urinary
      metabolite of melatonin, 6-sulfatoxymelatonin (aMT6s), corrected for creatinine
      levels, were measured in spot morning urine samples by immunoassay at baseline
      and 12 months. Changes in levels between exercisers and controls were compared
      using generalized estimating equations for linear regression. RESULTS: We
      observed no statistically significant difference in the change in aMT6s levels
      from baseline to 12 months in exercisers compared with controls (change in aMT6s
      levels: exercisers, +6.5%; controls, +13%; P = 0.66). There was no evidence of
      effect modification by age, sex, or body mass index. CONCLUSIONS: A 12-month
      moderate-intensity exercise intervention did not affect levels of aMT6s. IMPACT:
      Further research needs to focus on other potential mechanisms through which
      physical activity may reduce the risk of cancer. Cancer Epidemiol Biomarkers
      Prev; 23(8); 1696-9. (c)2014 AACR.

PMID- 24859869
TI  - Salivary auto-antibodies as noninvasive diagnostic markers of oral cavity
      squamous cell carcinoma.
AB  - BACKGROUND: Oral cavity squamous cell carcinoma (OSCC) is one of the most common
      cancers worldwide, and its incidence is still increasing. Approximately 50% of
      patients with OSCC die within 5 years after diagnosis, mostly ascribed to the
      fact that the majority of patients present advanced stages of OSCC at the time of
      diagnosis. METHODS: To discover salivary biomarkers for ameliorating the
      detection of OSCC, herein, we developed a multiplexed bead-based platform to
      simultaneously detect auto-antibodies (auto-Abs) in salivary samples. RESULTS:
      Compared with healthy individuals, the salivary levels of anti-p53, anti
      survivin, anti-Hsp60, and anti-RPLP0 were significantly elevated in patients with
      OSCC. Noteworthily, the elevated levels of anti-p53, anti-survivin, and anti
      Hsp60 were already observed in individuals with oral potentially malignant
      disorder. Moreover, the salivary levels of anti-p53, anti-survivin, anti-Hsp60,
      anti-RPLP0, and anti-CK8 were significantly elevated in patients with early-stage
      OSCC compared with those in healthy individuals. Most importantly, the use of a
      combined panel of salivary anti-p53, anti-survivin, anti-Hsp60, and anti-RPLP0
      largely improves the detection of OSCC. CONCLUSION: Collectively, our results
      reveal that the salivary auto-Abs are effective OSCC biomarkers and the four-auto
      Ab panel provides a novel and practicable approach for OSCC screening. IMPACT:
      This study provides the first evidence for the potential clinical application of
      salivary auto-Abs in OSCC diagnosis.

PMID- 24859870
TI  - Validating self-reported mammography use in vulnerable communities: findings and
      recommendations.
AB  - BACKGROUND: Most health surveys ask women whether they have had a recent
      mammogram, all of which report mammography use (past 2 years) at about 70% to 80%
      regardless of race or residence. We examined the potential extent of
      overreporting of mammography use in low income African-American and Latina women,
      and whether self-report inaccuracies might bias estimated associations between
      patient characteristics and mammography use. METHODS: Using venue-based sampling
      in two poor communities on the west side of Chicago, we asked eligible women
      living in two west side communities of Chicago to complete a survey about breast
      health (n = 2,200) and to provide consent to view their medical record. Of the
      1,909 women who screened eligible for medical record review, 1,566 consented
      (82%). We obtained medical records of all women who provided both permission and
      a valid local mammography facility (n = 1,221). We compared the self-reported
      responses from the survey with the imaging reports found in the medical record
      (documented). To account for missing data, we conducted multiple imputations for
      key demographic variables and report standard measures of accuracy. RESULTS:
      Although 73% of women self-reported a mammogram in the last 2 years, only 44% of
      self-reports were documented. Overreporting of mammography use was observed for
      all three ethnic groups. CONCLUSIONS: These results suggest considerable
      overestimation of prevalence of use in these vulnerable populations. IMPACT:
      Relying on known faulty self-reported mammography data as a measure of
      mammography use provides an overly optimistic picture of utilization, a problem
      that may be exacerbated in vulnerable minority communities.

PMID- 24859871
TI  - Increased lung and bladder cancer incidence in adults after in utero and early
      life arsenic exposure.
AB  - BACKGROUND: From 1958 to 1970, >100,000 people in northern Chile were exposed to
      a well-documented, distinct period of high drinking water arsenic concentrations.
      We previously reported ecological evidence suggesting that early-life exposure in
      this population resulted in increased mortality in adults from several outcomes,
      including lung and bladder cancer. METHODS: We have now completed the first study
      ever assessing incident cancer cases after early-life arsenic exposure, and the
      first study on this topic with individual participant exposure and confounding
      factor data. Subjects included 221 lung and 160 bladder cancer cases diagnosed in
      northern Chile from 2007 to 2010, and 508 age and gender-matched controls.
      RESULTS: ORs adjusted for age, sex, and smoking in those only exposed in early
      life to arsenic water concentrations of <=110, 110 to 800, and >800 MUg/L were
      1.00, 1.88 [95% confidence interval (CI), 0.96-3.71], and 5.24 (3.05-9.00;
      P(trend) < 0.001) for lung cancer, and 1.00, 2.94 (1.29-6.70), and 8.11 (4.31
      15.25; P(trend) < 0.001) for bladder cancer. ORs were lower in those not exposed
      until adulthood. The highest category (>800 MUg/L) involved exposures that
      started 49 to 52 years before, and ended 37 to 40 years before the cancer cases
      were diagnosed. CONCLUSION: Lung and bladder cancer incidence in adults was
      markedly increased following exposure to arsenic in early life, even up to 40
      years after high exposures ceased. Such findings have not been identified before
      for any environmental exposure, and suggest that humans are extraordinarily
      susceptible to early-life arsenic exposure. IMPACT: Policies aimed at reducing
      early-life exposure may help reduce the long-term risks of arsenic-related
      disease.

PMID- 24859873
TI  - Commentary: letter to the editor "do smoking and obesity really do not have any
      negative influence on wound healing after surgery of pilonidal disease?" of
      Cuneyt Kayaalp.

PMID- 24859872
TI  - Dietary insulin index and insulin load in relation to endometrial cancer risk in
      the Nurses' Health Study.
AB  - BACKGROUND: Although unopposed estrogen exposure is considered the main driver of
      endometrial carcinogenesis, factors associated with states of insulin resistance
      and hyperinsulinemia are independently associated with endometrial cancer risk.
      We used dietary insulin load and insulin index scores to represent the estimated
      insulin demand of overall diets and assessed their association with endometrial
      cancer risk in the prospective Nurses' Health Study. METHODS: We estimated
      incidence rate ratios (RR) and 95% confidence intervals (CI) for risk of invasive
      endometrial cancer using Cox proportional hazards models. Between the baseline
      dietary questionnaire (1980) and 2010, we identified a total of 798 incident
      invasive epithelial endometrial adenocarcinomas over 1,417,167 person-years of
      follow-up. RESULTS: Dietary insulin scores were not associated with overall risk
      of endometrial cancer. Comparing women in the highest with the lowest quintile,
      the multivariable-adjusted RRs of endometrial cancer were 1.07 (95% CI, 0.84
      1.35) for cumulative average dietary insulin load and 1.03 (95% CI, 0.82-1.31)
      for cumulative average dietary insulin index. Findings did not vary substantially
      by alcohol consumption, total dietary fiber intake, or body mass index and/or
      physical activity (P(heterogeneity) >= 0.10). CONCLUSIONS: Intake of a diet
      predicted to stimulate a high postprandial insulin response was not associated
      with endometrial cancer risk in this large prospective study. Considering the
      complex interplay of diet, lifestyle, and genetic factors contributing to the
      hyperinsulinemic state, dietary measures alone may not sufficiently capture
      absolute long-term insulin exposure. IMPACT: This study is the first to
      investigate dietary insulin scores in relation to endometrial cancer risk.

PMID- 24859874
TI  - Systematic review: outpatient management of acute uncomplicated diverticulitis.
AB  - PURPOSE OF REVIEW: Acute uncomplicated diverticulitis is traditionally managed by
      inpatient admission for bowel rest, intravenous fluids and intravenous
      antibiotics. In recent years, an increasing number of publications have sought to
      determine whether care might instead be conducted in the community, with earlier
      enteral feeding and oral antibiotics. This systematic review evaluates the safety
      and efficacy of such an ambulatory approach. METHODS: Medline, Embase and
      Cochrane Library databases were searched. All peer-reviewed studies that
      investigated the role of ambulatory treatment protocols for acute uncomplicated
      diverticulitis, either directly or indirectly, were eligible for inclusion.
      RESULTS: Nine studies were identified as being suitable for inclusion, including
      one randomised controlled trial, seven prospective cohort studies and one
      retrospective cohort study. All, except one, employed imaging as part of their
      diagnostic criteria. There was inconsistency between studies with regards to
      whether patients with significant co-morbidities were eligible for ambulatory
      care and whether bowel rest therapy was employed. Neither of these variables
      influenced outcome. Across all studies, 403 out of a total of 415 (97 %)
      participants were successfully treated for an episode of acute uncomplicated
      diverticulitis using an outpatient-type approach. Cost savings ranged from 35.0
      to 83.0 %. CONCLUSION: Current evidence suggests that a more progressive,
      ambulatory-based approach to the majority of cases of acute uncomplicated
      diverticulitis is justified. Based on this evidence, the authors present a
      possible outpatient-based treatment algorithm. An appropriately powered
      randomised controlled trial is now required to determine its safety and efficacy
      compared to traditional inpatient management.

PMID- 24859875
TI  - Genome-wide genotyping of acute myeloid leukemia with translocation
      t(9;11)(p22;q23) reveals novel recurrent genomic alterations.

PMID- 24859876
TI  - Outcomes of first-line treatment for chronic lymphocytic leukemia with 17p
      deletion.
AB  - Although uncommon in treatment-naive patients with chronic lymphocytic leukemia,
      deletion 17p is a high-risk disease characteristic. We analyzed and reported
      outcomes for 63 patients with deletion 17p chronic lymphocytic leukemia who
      received first-line therapy at our institution; at time of first treatment, 81%
      had unmutated immunoglobulin heavy chain variable gene and 58% had complex
      karyotype. Forty-nine patients (76%) received first-line fludarabine,
      cyclophosphamide, rituximab-based therapy, 6 (11%) received rituximab-based and 8
      (13%) received lenalidomide-based treatment. Overall, the complete plus nodular
      partial remission rate was 33%; on multivariable model, higher complete plus
      nodular partial remission rate was observed in patients with less than 50% cells
      positive for deletion 17p, and a higher probability of achieving at least a
      partial remission was observed with fludarabine, cyclophosphamide, rituximab
      based treatment. After a median follow up of 33 months (range 1-89 months), the
      estimated median progression-free survival was 14 months (95% confidence interval
      10-18) and estimated median overall survival was 63 months (95% confidence
      interval 43-83). In multivariable analysis, factors independently associated with
      longer progression-free survival were response to treatment and absence of
      complex karyotype. Achievement of complete plus nodular partial remission rate
      and mutated immunoglobulin heavy chain variable gene were independently
      associated with longer overall survival in multivariable model. Complex karyotype
      was associated with increased risk for Richter's transformation. New first-line
      strategies and agents must aim at both improving response and maintaining
      remission in patients with deletion 17p, particularly in the presence of complex
      karyotype. 

PMID- 24859878
TI  - Gamma heavy chain disease lacks the MYD88 L265p mutation associated with
      lymphoplasmacytic lymphoma.

PMID- 24859877
TI  - Increased mitochondrial apoptotic priming of human regulatory T cells after
      allogeneic hematopoietic stem cell transplantation.
AB  - CD4 regulatory T cells play a critical role in establishment of immune tolerance
      and prevention of graft-versus-host disease after allogeneic hematopoietic stem
      cell transplantation. The recovery and maintenance of regulatory T cells is
      dependent on homeostatic factors including the generation of naive regulatory T
      cells from hematopoietic precursor cells, the proliferation and expansion of
      mature regulatory T cells, and the survival of regulatory T cells in vivo. In
      this study, quantitation of mitochondrial apoptotic priming was used to compare
      susceptibility of regulatory T cells, conventional CD4 T cells and CD8 T cells to
      intrinsic pathway apoptosis in 57 patients after allogeneic hematopoietic stem
      cell transplantation and 25 healthy donors. In healthy donors, regulatory T cells
      are more susceptible to mitochondrial priming than conventional T cells.
      Mitochondrial priming is increased after hematopoietic stem cell transplantation
      in all T-cell subsets and particularly in patients with chronic graft-versus-host
      disease. Regulatory T cells express high levels of CD95 and are also more
      susceptible than conventional T cells to apoptosis through the extrinsic pathway.
      However, CD95 expression and extrinsic pathway apoptosis is not increased after
      hematopoietic stem cell transplantation. Decreased expression of BCL2 and
      increased expression of BIM, a mitochondrial cell death activator protein, in
      regulatory T cells contributes to increased mitochondrial priming in this T-cell
      subset but additional factors likely contribute to increased mitochondrial
      priming following hematopoietic stem cell transplantation. 

PMID- 24859879
TI  - Efficacy of bortezomib, cyclophosphamide and dexamethasone in treatment-naive
      patients with high-risk cardiac AL amyloidosis (Mayo Clinic stage III).
AB  - Bortezomib is an active agent in AL amyloidosis and responses to this drug in
      combination with cyclophosphamide and dexamethasone are both rapid and deep. Here
      we present an international, multicenter series of 60 patients with Mayo Clinic
      stage III cardiac amyloidosis to assess the impact of this regimen in improving
      outcomes in this poor-risk group. The median follow-up for the entire cohort is
      11.8 months. The overall response rate was 68%. In a landmark analysis, examining
      patients who survived more than 3 months, the overall response rate was 86%. A
      cardiac response was seen in 32% of patients. The estimated 1-year survival rate
      for the whole cohort was 57% and 24 patients (40%) died while on therapy.
      Although unable to save the poorest risk patients, the combination of bortezomib,
      cyclophosphamide and dexamethasone can achieve a high number of hematologic and
      cardiac responses, likely improving overall survival and justifying a prospective
      trial. 

PMID- 24859880
TI  - SIGLEC-G deficiency increases susceptibility to develop B-cell
      lymphoproliferative disorders.
AB  - The sialic-acid-binding immunoglobulin-like lectin SIGLEC-G is a negative
      regulator of B-cell receptor-mediated calcium signaling. Its deficiency leads to
      reduced turnover and increased proliferation and survival of murine B-1a cells.
      Siglecg(-/-) mice show a premature expansion of polyclonal CD5(+) B cells in the
      spleen and the peritoneal cavity. Here we studied the fate of B lymphocytes in
      Siglecg(-/-) mice over time. We demonstrate that in aging animals SIGLEC-G
      deficiency promotes progressive accumulation of monoclonal B lymphocytes and
      increases the susceptibility to develop B-cell lymphoproliferative disorders.
      Lymphoid tumors arising in aged Siglecg(-/-) mice are monoclonal and
      histologically heterogeneous as they include diffuse large B-cell lymphoma,
      follicular lymphoma, and medium-to-large B-cell monomorphic lymphoma but
      surprisingly not chronic lymphocytic leukemia. The tumors express high levels of
      BCL-2 and are transplantable. In keeping with these findings we have also
      observed a remarkable down-regulation of the human ortholog SIGLEC10 in human B
      cell lymphoma and leukemia cell lines. Taken together, these observations
      indicate that the down-regulation of negative B-cell receptor regulators such as
      SIGLEC-G/SIGLEC10 may represent another mechanism relevant to the pathogenesis of
      B-cell lymphomas. 

PMID- 24859881
TI  - Endoscopic management of choledochocele complicated with choledocholithiasis and
      pancreatitis in an old patient.
AB  - Choledochocele, or type III choledochal cyst, is a rare congenital disease and is
      even less common among adults compared with children. In this case, a 75-year-old
      female was admitted to our hospital presented with epigastric pain and vomiting
      for one day. Abdominal computed tomography revealed dilated common bile duct,
      pancreatitis and peripancreatic effusion. The patient was treated with fasting,
      fluid resuscitation, anti-acid agents, somatostatin and antibiotics. Endoscopic
      retrograde cholangiopancreatography was employed for the further diagnosis of
      choledochocele, choledocholithiasis and biliary stenosis. Endoscopic
      sphincterotomy, stone extraction and plastic stent placement were performed for
      treatment. The patient recovered quickly after the treatment and no signs of
      recurrence and complications were observed during the first follow-up. Endoscopic
      management may be a promising and alternative therapy for choledochocele although
      long-term follow-up is necessary to confirm the efficacy and safety of this
      procedure in the future. 

PMID- 24859882
TI  - Multimorbidity in women with and without osteoporosis: results from a large US
      retrospective cohort study 2004-2009.
AB  - To determine the incidence of comorbidities in women with and without
      osteoporosis, incidence rates per 1,000 person-years were calculated using
      electronic health records from an integrated healthcare system. The overall
      comorbidity burden and health service utilization were greater in women with
      osteoporosis than in the controls. INTRODUCTION: This retrospective cohort study
      describes the incidence of an array of comorbidities in women with and without
      osteoporosis (OP). METHODS: Using electronic health records from an integrated
      healthcare system, we identified 22,414 women aged 55-89 years with OP and 22,414
      age-matched controls without OP. Incidence rates (IRs) per 1,000 person-years (P
      Y) were calculated and 95% confidence intervals (CI) were estimated. RESULTS:
      Women with OP had significantly more comorbidities, medications,
      hospitalizations, and outpatient visits than the controls. Most cardiac
      comorbidity rates were 20-25% lower in the OP cohort than in the control cohort.
      Hypertension had the largest rate difference; the IR was 42.0 per 1,000 P-Y (95%
      CI 40.2-44.0) in the OP cohort compared to 94.0 (95% CI 90.7-97.4) in the control
      cohort. Rates for cerebrovascular disease were similar for both cohorts at 26 per
      1,000 P-Y. Bronchitis, sinusitis, and cystitis were each 55 per 1,000 P-Y in the
      OP cohort, whereas they ranged from 28 to 34 per 1,000 P-Y in the controls. The
      OP cohort had decreased incidence of ovarian, uterine, colorectal, and liver
      cancers and increased incidence of lung cancer, breast cancer, and multiple
      myeloma, compared to the non-OP cohort. Falls, depression, vision, and
      musculoskeletal issues were higher for the OP cohort than the controls.
      CONCLUSIONS: This study demonstrates the high disease burden in women with OP.
      This knowledge may help guide the clinical management of this population and may
      aid in the interpretation of adverse events in randomized clinical trials of OP
      therapies.

PMID- 24859883
TI  - Global forecasting of thermal health hazards: the skill of probabilistic
      predictions of the Universal Thermal Climate Index (UTCI).
AB  - Although over a hundred thermal indices can be used for assessing thermal health
      hazards, many ignore the human heat budget, physiology and clothing. The
      Universal Thermal Climate Index (UTCI) addresses these shortcomings by using an
      advanced thermo-physiological model. This paper assesses the potential of using
      the UTCI for forecasting thermal health hazards. Traditionally, such hazard
      forecasting has had two further limitations: it has been narrowly focused on a
      particular region or nation and has relied on the use of single 'deterministic'
      forecasts. Here, the UTCI is computed on a global scale, which is essential for
      international health-hazard warnings and disaster preparedness, and it is
      provided as a probabilistic forecast. It is shown that probabilistic UTCI
      forecasts are superior in skill to deterministic forecasts and that despite
      global variations, the UTCI forecast is skilful for lead times up to 10 days. The
      paper also demonstrates the utility of probabilistic UTCI forecasts on the
      example of the 2010 heat wave in Russia. 

PMID- 24859884
TI  - Acquisition of Paleolithic toolmaking abilities involves structural remodeling to
      inferior frontoparietal regions.
AB  - Human ancestors first modified stones into tools 2.6 million years ago,
      initiating a cascading increase in technological complexity that continues today.
      A parallel trend of brain expansion during the Paleolithic has motivated over 100
      years of theorizing linking stone toolmaking and human brain evolution, but
      empirical support remains limited. Our study provides the first direct
      experimental evidence identifying likely neuroanatomical targets of natural
      selection acting on toolmaking ability. Subjects received MRI and DTI scans
      before, during, and after a 2-year Paleolithic toolmaking training program. White
      matter fractional anisotropy (FA) showed changes in branches of the superior
      longitudinal fasciculus leading into left supramarginal gyrus, bilateral ventral
      precentral gyri, and right inferior frontal gyrus pars triangularis. FA increased
      from Scan 1-2, a period of intense training, and decreased from Scan 2-3, a
      period of reduced training. Voxel-based morphometry found a similar trend toward
      gray matter expansion in the left supramarginal gyrus from Scan 1-2 and a
      reversal of this effect from Scan 2-3. FA changes correlated with training hours
      and with motor performance, and probabilistic tractography confirmed that white
      matter changes projected to gray matter changes and to regions that activate
      during Paleolithic toolmaking. These results show that acquisition of Paleolithic
      toolmaking skills elicits structural remodeling of recently evolved brain regions
      supporting human tool use, providing a mechanistic link between stone toolmaking
      and human brain evolution. These regions participate not only in toolmaking, but
      also in other complex functions including action planning and language, in
      keeping with the hypothesized co-evolution of these functions.

PMID- 24859885
TI  - Stromal fibroblasts are predictors of disease-related mortality in esophageal
      squamous cell carcinoma.
AB  - The growth, invasiveness and metastasis of human cancers are determined not only
      by cancer cells, but also by their microenvironment. Activated stromal
      fibroblasts promote tumor progression by secreting growth factors. In the present
      study, we focused on interrelations between cancer and fibroblasts, the main
      component of tumor stroma. We retrospectively analyzed the relations of mortality
      to clinical, pathological, and alpha-smooth muscle actin (alpha-SMA)
      characteristics in 97 consecutive patients with esophageal squamous cell
      carcinoma (ESCC). In vitro, we used TE-11, KYSE150 and KYSE220 ESCC cell lines
      and isolated esophageal stromal fibroblasts, some of which were immortalized.
      Migration assays were conducted to assess the effects of fibroblasts on cancer
      cell migration and 3-dimensional organotypic cultures. In vivo, TE-11 and KYSE220
      cells plus immortalized fibroblasts were co-transplanted subcutaneously in
      Nod/Scid mice to assess the effects of fibroblasts on tumorigenicity.
      Clinicopathologically, the alpha-SMA expression of cancer stroma was correlated
      with venous invasion (p<0.01), nodal involvement (p=0.02), recurrence (p=0.01),
      and was a predictor of survival in patients with stage I and II ESCC (p=0.04). In
      vitro, the presence of fibroblasts strongly promoted the migration of TE-11,
      KYSE150 and KYSE220 cells. On organotypic culture, stromal invasion was observed
      only in the presence of immortalized fibroblasts. In vivo, tumors developed or
      grew in a fibroblast-dependent manner after implantation. Our findings provide
      evidence that stromal fibroblasts and tumor cells interact to promote tumor
      progression in ESCC. In patients with earlier stage ESCC, alpha-SMA may be a
      predictor of mortality. Inhibition of paracrine systems associated with tumor
      fibroblasts may slow or reverse tumor progression, potentially leading to the
      development of new targeted therapies.

PMID- 24859886
TI  - Loss of SNAIL inhibits cellular growth and metabolism through the miR-128
      mediated RPS6KB1/HIF-1alpha/PKM2 signaling pathway in prostate cancer cells.
AB  - SNAIL is a promising target for the treatment of cancer because it is known to
      promote epithelial-mesenchymal transition. Recent studies suggest that SNAIL also
      takes part in metabolic reprogramming and chemotherapy resistance in some
      cancers. In prostate cancer (PCa), SNAIL has been proved to be required for
      hypoxia-induced invasion and as a potential marker for predicting the recurrence.
      However, the role of SNAIL in PCa aberrant metabolism is poorly understood. In
      this study, we identified that SNAIL regulated cellular growth and energy
      metabolism through the miR-128-mediated ribosomal protein S6 kinase 1
      (RPS6KB1)/HIF-1alpha/PKM2 signaling pathway which played a key role in the
      reprogramming of cancer metabolism. Using quantitative RT-PCR (qRT-PCR), we found
      that SNAIL expression was elevated in castration-resistant prostate cancer
      tissues compared with androgen-dependent prostate cancer tissues and nontumorous
      tissues. Depletion of SNAIL increased miR-128 expression levels, inhibited cell
      growth, reduced glucose consumption and lactate production, and repressed the
      expression of RPS6KB1, HIF-1alpha, and PKM2 in PCa cells. Luciferase reporter
      assays showed the SNAIL regulated miR-128 expression at the transcriptional level
      and miR-128 modulated RPS6KB1 expression at the translational level. Furthermore,
      down-expression of miR-128 partially restored the effect of si-SNAIL on the
      suppression of cellular growth, metabolism, and RPS6KB1/HIF-1alpha/PKM2 signaling
      pathway. To our knowledge, it is the first time to demonstrate that SNAIL/miR
      128/RPS6KB1 pathway plays a critical role in the progression of PCa.

PMID- 24859887
TI  - Diagnostic value of computed tomography scanning in differentiating malignant
      from benign solitary pulmonary nodules: a meta-analysis.
AB  - An early diagnosis of lung cancer is crucial for early treatment and management.
      The objective of this systematic review was to assess the overall diagnostic
      accuracy of chest computed tomography (CT) scanning in differentiating malignant
      from benign solitary pulmonary nodules (SPNs) with meta-analysis. The PubMed and
      China National Knowledge Infrastructure (CNKI) database were searched for
      eligible studies published up to March 2014. The sensitivity, specificity, and
      other measures of accuracy of chest CT scanning in the diagnosis of SPNs were
      pooled along with 95 % confidence intervals (CI). Summary receiver operating
      characteristic (ROC) curves were used to summarize overall test performance.
      Thirty-two studies met our inclusion criteria. The summary estimates for chest CT
      scanning in the diagnosis of SPNs in the meta-analysis were as follows: pooled
      sensitivity, 0.89 (95 % CI, 0.88 to 0.91); pooled specificity, 0.70 (95 % CI,
      0.68 to 0.73); positive likelihood ratio, 2.88 (95 % CI, 2.46 to 3.37); negative
      likelihood ratio, 0.16 (95 % CI, 0.12 to 0.21); and diagnostic odds ratio, 23.83
      (95 % CI, 16.18 to 35.11). The results indicate that CT scanning has relatively
      high sensitivity and moderate specificity for the diagnosis of SPNs. Given the
      low cost and growing prevalence of the technology, CT scanning should be
      recommended as the initial test for the evaluation of SPNs.

PMID- 24859889
TI  - Thermal transport and thermoelectric properties of beta-graphyne nanostructures.
AB  - Graphyne, an allotrope of graphene, is currently a hot topic in the carbon-based
      nanomaterials research community. Taking beta-graphyne as an example, we
      performed a comprehensive study of thermal transport and related thermoelectric
      properties by means of nonequilibrium Green's function (NEGF). Our simulation
      demonstrated that thermal conductance of beta-graphyne is only approximately 26%
      of that of the graphene counterpart and also shows evident anisotropy. Meanwhile,
      thermal conductance of armchair beta-graphyne nanoribbons (A-BGYNRs) presents
      abnormal stepwise width dependence. As for the thermoelectric property, we found
      that zigzag beta-graphyne nanoribbons (Z-BGYNRs) possess superior thermoelectric
      performance with figure of merit value achieving 0.5 at room temperature, as
      compared with graphene nanoribbons (~0.05). Aiming at obtaining a better
      thermoelectric coefficient, we also investigated Z-BGYNRs with geometric
      modulations. The results show that the thermoelectric performance can be enhanced
      dramatically (figure of merit exceeding 1.5 at room temperature), and such
      enhancement strongly depends on the width of the nanoribbons and location and
      quantity of geometric modulation. Our findings shed light on transport properties
      of beta-graphyne as high efficiency thermoelectrics. We anticipate that our
      simulation results could offer useful guidance for the design and fabrication of
      future thermoelectric devices.

PMID- 24859890
TI  - Evaluation of the effect of the modified early warning system on the nurse-led
      activation of the rapid response system.
AB  - The modified early warning system (MEWS) is a scoring rubric used to detect the
      earliest signs of a change in a patient's condition. This mixed-methods study
      used pre- and postintervention data to describe the impact of the MEWS on the
      frequency of rapid response system activations and cardiopulmonary arrests among
      patients admitted to medical-surgical units. Focus groups of nursing staff
      provided insight into the factors that influence how nurses use the MEWS at the
      bedside as a framework to identify, intervene, and manage patients in need of an
      advanced level of care.

PMID- 24859888
TI  - Identification of a novel cognate cytosolic Hsp70 gene (MnHsc70-2) from oriental
      river prawn Macrobrachium nipponense and comparison of its expressions with the
      first cognate Hsc70 (MnHsc70-1) under different stresses.
AB  - The 70-kDa family of heat-shock proteins (Hsp70) plays an important role in the
      host immunity, which is widely expressed in eukaryotic cells as a major chaperone
      protein. In the present study, the full-length complementary DNA (cDNA) of a
      second cognate cytosolic Hsp70 family member (MnHsc70-2) was cloned and
      characterized from Macrobrachium nipponense, which is an economically and
      nutritionally important crustacean. The cDNA was 2,717 bp, containing an open
      reading frame (ORF) of 1,950 bp, which encodes a protein of 649 amino acids with
      a theoretical molecular weight of 71.1 kDa and an isoelectric point of 5.27.
      Sequence alignment showed that the MnHsc70-2 shared 75-97 % identity with other
      heat-shock proteins. Compared to the previously identified cognate Hsp70 (MnHsc70
      1) in M. nipponense, MnHsc70-2 showed quite different expression profiles under
      unstressed conditions in all tested tissues, including the hemocytes, heart,
      hepatopancreas, gill, intestine, nerve, and muscle. The phylogenetic analysis
      demonstrated that MnHsc70-2 showed the closest relationship with MnHsc70-1. Heat
      inducibility assays showed that two isolated messenger RNAs (mRNAs) displayed
      different expression profiles in both the hepatopancreas and gill tissues.
      MnHsc70-1 mRNA expression level decreased at first and then increased to the
      normal level, whereas MnHsc70-2 mRNA level increased at first and then decreased.
      The expressions of two MnHsc70s showed substantial obvious heat-inducible
      regulation in both the hepatopancreas and gill. Under bacterial challenge by
      Aeromonas hydrophila, both MnHsc70-1 and MnHsc70-2 mRNA level was up-regulated
      moderately. The results suggested that two cognate Hsc70s may play essential
      functions in mediating responses to heat-shock and bacterial challenge.

PMID- 24859891
TI  - Franklin Delano Roosevelt: a famous patient.
AB  - Franklin Delano Roosevelt is arguably one of the greatest of American Presidents.
      His encounter with the polio that crippled him at an early age and its
      transformative impact upon him are here discussed with particular reference to
      his relationship with his physician, Dr. George Draper. This transformation
      liberated energy in Roosevelt to lead and to show empathy for others in ways that
      both challenged the political and social status quo in the U.S.A. as well as
      helped save the world from the threat of Fascism in World War II. This essay
      seeks to demonstrate how an investigation of the life and struggles of this
      famous patient is one avenue for relating the study of the humanities to medical
      education. An earlier version of this paper was presented as the Heberden Lecture
      in the History of Medicine at the New York Academy of Medicine in 2012.

PMID- 24859892
TI  - GLP-1 ameliorates the proliferation activity of INS-1 cells inhibited by
      intermittent high glucose concentrations through the regulation of cyclins.
AB  - Glucagon-like peptide-1 (GLP-1) and its analog exendin (EX)-4 have been
      considered to promote beta-cell growth and expansion. In the present, study we
      investigated the effect of GLP-1 on proliferative activity and cell cycle
      regulation in the pancreatic insulin-secreting beta-cell line, INS-1, treated
      with intermittent high glucose. INS-1 cells were treated with normal glucose (5.5
      mmol/l), constant high glucose (30 mmol/l) and intermittent high glucose
      (rotation/24 h in 5.5 or 30 mmol/l) in the presence or absence of GLP-1 (100
      nmol/l) for seven days. Proliferative activity, cell cycle and the expression of
      cyclin D1, p21, p27 and Skp2 were examined. INS-1 treated with intermittent high
      glucose and GLP-1 demonstrated a significant increase in proliferation activity
      (1.45+/-0.12; P<0.01) and decreased cell proportion in G0/G1 phase (49.73+/
      4.04%, P<0.01) compared with those without GLP-1. Furthermore, the expression
      levels of cyclin D1 and Skp2 were increased, while the expression of p27 and p21
      were significantly reduced. Similar results were identified in those treated with
      constant high glucose and GLP-1. These results suggest that GLP-1 may ease the
      G0/G1 cell cycle arrest of INS-1 cells induced by intermittent high glucose by
      upregulating the expression of cyclin D1 and Skp2, downregulating the expression
      of p21 and p27, and finally promoting the cell cycle progression and
      proliferation activity. 

PMID- 24859894
TI  - Disturbed oxidant/antioxidant balance in aqueous humour of patients with
      exfoliation syndrome.
AB  - PURPOSE: To establish the total oxidant status (TOS), total antioxidant capacity
      (TAC) and oxidative stress index (OSI) of the aqueous humour in patients
      presenting exfoliation syndrome (EXS) without glaucoma. METHODS: The TOS, TAC and
      OSI of the aqueous humour of patients with EXS (group 1, n = 17) and patients
      without EXS (group 2, n = 25) who underwent cataract surgery were evaluated.
      Samples were measured spectrophotometrically using a colourimetric method. The
      Mann-Whitney U, independent-samples t tests, Pearson correlation and analysis of
      covariance tests were used in the statistical analyses. RESULTS: The mean TOS in
      group 1 and 2 patients was 57.6 +/- 32.4 and 30.4 +/- 22.6 mmol/L, respectively,
      which is a statistically significant difference (p = 0.001). The mean TAC level
      in group 1 and 2 patients was 2.3 +/- 0.7 and 2.5 +/- 0.7 mmol/L, respectively,
      and although TAC was decreased in group 1 relative to group 2, the difference was
      not statistically significant (p = 0.55). The mean OSI in group 1 and 2 patients
      was 27.4 +/- 17.1 and 12.5 +/- 8.3 mmol/L, respectively, with the mean OSI level
      statistically higher in group 1 (p = 0.03). CONCLUSION: Our findings provide
      evidence that the aqueous humour of EXS patients is characterised by increased
      oxidative stress and a disturbed oxidant/antioxidant balance. The increased
      oxidative stress and decreased levels of antioxidants in ocular fluids of EXS
      patients may play a significant role in the pathogenesis and complications of
      EXS.

PMID- 24859893
TI  - Exercise effects on polyp burden and immune markers in the ApcMin/+ mouse model
      of intestinal tumorigenesis.
AB  - Many observational epidemiologic studies suggest an association between exercise
      and colon cancer risk. The mechanisms contributing to a preventative effect of
      exercise on colon cancer are complex and multifaceted. Altered immune system
      function is one possible mechanism that has been largely unexplored. Therefore,
      the purpose of this study was to examine the effects of exercise on markers
      associated with macrophages and select T cell populations in a mouse model of
      intestinal tumorigenesis and to relate this to polyp characteristics. Male
      Apc(Min/+) mice were randomly assigned to either sedentary (Sed) or exercise (Ex)
      treatment (n=6-9/group). The exercise treatment consisted of treadmill running
      for 1 h/day and 6 days a week at 15 m/min from 4 until 16 weeks of age.
      Intestinal polyps were counted and categorized by size. Mucosal tissue was
      analyzed for mRNA expression of overall macrophages (F4/80), for genes associated
      with M1 (IL-12, IL-23 and Nos2) and M2 (CD206, IL-10, IL-4, CCL17, CCL22 and Arg
      1) macrophages and the macrophage chemoattractants MCP-1, fetuin A and CXCL14.
      Markers for cytotoxic T cells (CTLs) and regulatory T cells were also examined by
      measuring mRNA expression of CD8 and Foxp3, respectively. While there was no
      significant difference in overall polyp number between the groups (Sed, 23.3+/
      4.3; and Ex, 16.5+/-4.3), Ex did have a reduction in the number of large polyps
      (Sed, 6.1+/-1.1; and Ex, 3.0+/-0.6) (P<0.05). This was consistent with a decrease
      in spleen weight (P<0.05). Similarly, Ex reduced mRNA expression of overall
      macrophages (F4/80) as well as markers associated with both M1 (IL-12) and M2
      (CD206, CCL22 and Arg-1) subtypes (P<0.05) but there was no significant decrease
      in macrophage chemoattractants. CD8 expression was increased while Foxp3
      expression was decreased with Ex (P<0.05). Overall the data provide important new
      information on immune regulation as a possible mechanism for the documented
      benefits of exercise training on reducing colon cancer progression.

PMID- 24859895
TI  - Temperature changes and chondrocyte death during drilling in a bovine cartilage
      model and chondroprotection by modified irrigation solutions.
AB  - PURPOSE: Drilling into cartilage/bone is often required for orthopaedic surgery.
      While drilling into bone has been studied, the response of cartilage has received
      little attention. We have measured cartilage and drill bit temperatures during
      drilling and quantified the zone of chondrocyte death (ZCD) around the hole in
      the presence/absence of irrigation solutions. METHODS: Drilling was performed
      using a 1.5-mm orthopaedic drill bit applied to bovine metatarsophalangeal joints
      and temperatures recorded by infrared camera. Osteochondral explants were then
      incubated with 5-chloromethylfluorescein diacetate (CMFDA) and propidium iodide
      (PI) to label living/dead chondrocytes respectively. The width of the ZCD was
      quantified by confocal laser scanning microscopy (CLSM) and image analysis.
      RESULTS: Without irrigation, the ZCD following drilling for two seconds was 135
      +/- 15 MUm and this increased (>fourfold, P < 0.001) with five seconds of
      drilling. Irrigation reduced the ZCD following drilling for both two and five
      seconds (P < 0.05, P < 0.001 respectively) to the same level (approx. 60 MUm).
      Without irrigation, drill bit and cartilage temperature increased rapidly to >265
      and 119  degrees C respectively, whereas the camera saturated at >282  degrees C
      during drilling for five seconds. With irrigation, the drill bit temperature was
      significantly reduced during drilling for two and five seconds (approx. 90 
      degrees C) with negligible change in cartilage temperature. Drilling while
      irrigating with hyperosmotic saline (600 mOsm) reduced (P < 0.01) the ZCD
      compared to saline, whereas chondrocyte death was increased (P < 0.01) by Ca(2+)
      saline (5 mM). CONCLUSIONS: Reducing temperature during drilling by irrigation
      markedly suppressed, but did not abolish chondrocyte death. Optimising the
      irrigation solution by raising osmolarity and reducing Ca(2+) content
      significantly reduced chondrocyte death during drilling and may be clinically
      beneficial.

PMID- 24859896
TI  - Surgical treatment of lumbar spondylodiscitis: a comparison of two methods.
AB  - PURPOSE: This study evaluates two basic hypotheses: (1) the risk of an isolated
      dorsal approach to ventral lumbar spondylodiscitis based on clinical and
      radiographic results and (2) the risk of anterior radical debridement due to
      using a titanium implant in the site of bone infection. METHODS: Group A
      consisting of 23 patients was treated only by a dorsal transmuscular approach and
      group B consisting of eight patients was treated by two-stage posteroanterior
      surgery. Both evaluated groups were assessed before surgery, six weeks and one
      year after surgery with the Japanese Orthopaedic Association (JOA) score, visual
      analogue scale (VAS) and Kirkaldy-Willis functional criteria. To evaluate the
      sagittal balance restoration, measurement by the Cobb modified angle of the
      affected segment was performed. RESULTS: Differences (p < 0.001) in group A were
      found between JOA values before surgery (average 9.30) and at six weeks after
      surgery (average 11.82) and 12 months after surgery (13.27) and VAS differences
      before surgery (average 7.39), six weeks after surgery (average 3.82) and 12
      months after surgery (average 2.36) in group A. According to the Kirkaldy-Willis
      functional criteria, 11 patients were evaluated as excellent, nine patients as
      good and two patients as poor. The values of the JOA score in group B showed an
      improvement compared with the JOA values before surgery (average 9.38) at six
      weeks after surgery (average 11.75) and 12 months after surgery (average 13.63),
      and the VAS score before surgery (average 7.38) was found to have improved six
      weeks after surgery (average 4.63) and 12 months after surgery (average 2.25).
      The functional evaluation according to the Kirkaldy-Willis functional criteria
      assessed three patients as excellent, four patients as good and one patient as
      fair. Radiographic examinations of group A revealed the following findings before
      surgery (average 1.75), six months after surgery (average -3.73) and 12 months
      after surgery (average -0.79) and in group B before surgery (average 3.71), six
      weeks after surgery (average -8.21) and 12 months after surgery (average -6.45).
      CONCLUSIONS: The results demonstrate the minimum serious surgical complications
      and greater loss of sagittal balance without clinical correlation in group A. We
      did not find any relapse or persistence of the infection in the post-operative
      period in group B.

PMID- 24859897
TI  - Trends in epidemiology and patho-anatomical pattern of proximal humeral
      fractures.
AB  - PURPOSE: Proximal humeral fractures are common and frequently associated with
      osteoporosis. Little is known about the association between the patho-anatomical
      fracture pattern of proximal humeral fractures and patient characteristics. The
      purpose of this six year longitudinal registry analysis of proximal humeral
      fractures was to study overall numbers, certain predefined pathoanatomical
      patterns and distribution compared with specific patient characteristics.
      METHODS: Data of patients treated between 2006 and 2011 in a country hospital
      that provides care >95 % of the city's hospitalised patients with fractures was
      retrospectively reviewed. Data were analysed according to patient characteristics
      of age, gender, comorbidity, accompanying injuries and radiological analysis of
      pathoanatomical fracture patterns based on Neer and Arbeitsgemeinschaft fur
      Osteosynthesefragen (AO) classification. RESULTS: Eight hundred and fifteen
      proximal humeral fractures (67% women/33% men; mean age 66 years, range 19-99)
      were analysed. During the study period, an overall increase of 42.5% was found:
      according to AO classification, 46% were type A, 22% type B and 32% type C. Based
      on the Neer classification, 86% were displaced, and 49% were complex with more
      than three parts. Of complex fractures, 57% were female patients >60 years. The
      number of complex fractures was five times higher in women >60 years than in men
      of the same age group. CONCLUSIONS: An overall increase of inpatients with
      displaced proximal tibial fractures was documented. Interestingly, complex
      displaced proximal humeral fractures, especially in older women with
      comorbidities, accounted for the majority of cases. These results suggest that
      health-care planning and hospital-based therapeutic strategies should focus on
      this patient group.

PMID- 24859898
TI  - Osseointegration of polyethylene implants coated with titanium and biomimetically
      or electrochemically deposited hydroxyapatite in a rabbit model.
AB  - PURPOSE: The aim of this study was to evaluate the osseointegration of a new
      coating directly deposited on PE at room temperature. METHODS: Thirty-six (36)
      male New Zealand rabbits were randomly assigned to receive one out of three types
      of implants: two tested implants, i.e. PE implant coated with TiPVD and
      biomimetic HA (biomimetic), PE implant coated with TiPVD and electrolytic HA
      (electrolytic), and positive control made of massive microrough titanium coated
      with plasma sprayed HA (TiHAPS). Osseointegration was evaluated by
      histomorphometry (bone tissue in contact [BIC]), mineralized bone area [MBA]) and
      mechanical testing (push-out test, interfacial shear strength [ISS]) at six and
      12 weeks in the distal femurs. RESULTS: For BIC there were no differences between
      the groups at six (p = 0.98) and 12 weeks (p = 0.13). For MBA, no statistically
      significant difference was measured between groups at six (p = 0.52) and 12 weeks
      (p = 0.57). At six weeks, interfacial shear strength (ISS) was significantly
      higher (p = 0.01) for TiHAPs implants compared to biomimetic and electrolytic
      implants. This difference was not significant at 12 weeks (p = 0.92). CONCLUSION:
      The osseointegration of biomimetic and electrolytic implants was equivalent to a
      positive control at 12 weeks.

PMID- 24859899
TI  - The Balkan beam - Florschutz frame and its use during the Great War.
AB  - We remember the military medical practice of Croatian surgeon, Vatroslav
      Florschutz (1879-1967), known for his invention of the traction frame for
      repositioning bone fracture fragments of the upper and lower extremities. The
      method, known as the Balkan frame / beam or Balkan splint, was introduced and
      published in 1911 and used in war medicine thereafter. The memory of this
      invention adds to our orthopaedic heritage and sheds light on its creator working
      under the most demanding war circumstances. On the occasion of the 100th
      anniversary of the outbreak of World War I, reminiscence of Florschutz's war
      experience, his orthopaedic innovation and other innovations contributes to our
      understanding of human efforts to save lives and restore bodily function of the
      wounded during wars. 

PMID- 24859900
TI  - Should we advise patients with sutures not to swim?

PMID- 24859901
TI  - Interpreting raised serum prolactin results.

PMID- 24859903
TI  - Surgeon volume and early complications after primary total hip arthroplasty.

PMID- 24859904
TI  - What is an open label trial?

PMID- 24859905
TI  - GP leader warns funding shortfalls could result in services closing.

PMID- 24859902
TI  - Relation between surgeon volume and risk of complications after total hip
      arthroplasty: propensity score matched cohort study.
AB  - OBJECTIVES: To identify a cut point in annual surgeon volume associated with
      increased risk of complications after primary elective total hip arthroplasty and
      to quantify any risk identified. DESIGN: Propensity score matched cohort study.
      SETTING: Ontario, Canada. PARTICIPANTS: 37,881 people who received their first
      primary total hip arthroplasty during 2002-09 and were followed for at least two
      years after their surgery. MAIN OUTCOME MEASURE: The rates of various surgical
      complications within 90 days (venous thromboembolism, death) and within two years
      (infection, dislocation, periprosthetic fracture, revision) of surgery. RESULTS:
      Multivariate splines were developed to visualize the relation between surgeon
      volume and the risk for various complications. A threshold of 35 cases a year was
      identified, under which there was an increased risk of dislocation and revision.
      6716 patients whose total hip arthroplasty was carried out by surgeons who had
      done <= 35 such procedure in the previous year were successfully matched to
      patients whose surgeon had carried out more than 35 procedures. Patients in the
      former group had higher rates of dislocation (1.9% v 1.3%, P=0.006; NNH 172) and
      revision (1.5% v 1.0%, P=0.03; NNH 204). CONCLUSIONS: In a cohort of first time
      recipients of total hip arthroplasty, patients whose operation was carried by
      surgeons who had performed 35 or fewer such procedures in the year before the
      index procedure were at increased risk for dislocation and early revision.
      Surgeons should consider performing 35 cases or more a year to minimize the risk
      for complications. Furthermore, the methods used to visualize the relationship
      between surgeon volume and the occurrence of complications can be easily applied
      in any jurisdiction, to help inform and optimize local healthcare delivery.

PMID- 24859906
TI  - NHS will collapse without "building blocks" of general practice, warns GP leader.

PMID- 24859907
TI  - Assessment of panobacumab as adjunctive immunotherapy for the treatment of
      nosocomial Pseudomonas aeruginosa pneumonia.
AB  - The fully human anti-lipopolysaccharide (LPS) immunoglobulin M (IgM) monoclonal
      antibody panobacumab was developed as an adjunctive immunotherapy for the
      treatment of O11 serotype Pseudomonas aeruginosa infections. We evaluated the
      potential clinical efficacy of panobacumab in the treatment of nosocomial
      pneumonia. We performed a post-hoc analysis of a multicenter phase IIa trial
      (NCT00851435) designed to prospectively evaluate the safety and pharmacokinetics
      of panobacumab. Patients treated with panobacumab (n = 17), including 13 patients
      receiving the full treatment (three doses of 1.2 mg/kg), were compared to 14
      patients who did not receive the antibody. Overall, the 17 patients receiving
      panobacumab were more ill. They were an average of 72 years old [interquartile
      range (IQR): 64-79] versus an average of 50 years old (IQR: 30-73) (p = 0.024)
      and had Acute Physiology and Chronic Health Evaluation II (APACHE II) scores of
      17 (IQR: 16-22) versus 15 (IQR: 10-19) (p = 0.043). Adjunctive immunotherapy
      resulted in an improved clinical outcome in the group receiving the full three
      course panobacumab treatment, with a resolution rate of 85 % (11/13) versus 64 %
      (9/14) (p = 0.048). The Kaplan-Meier survival curve showed a statistically
      significantly shorter time to clinical resolution in this group of patients (8.0
      [IQR: 7.0-11.5] versus 18.5 [IQR: 8-30] days in those who did not receive the
      antibody; p = 0.004). Panobacumab adjunctive immunotherapy may improve clinical
      outcome in a shorter time if patients receive the full treatment (three doses).
      These preliminary results suggest that passive immunotherapy targeting LPS may be
      a complementary strategy for the treatment of nosocomial O11 P. aeruginosa
      pneumonia. 

PMID- 24859908
TI  - Distribution of 13 virulence genes among clinical and environmental Aeromonas
      spp. in Western Australia.
AB  - We evaluated the pathogenic potential of 98 clinical and 31 environmental
      Aeromonas isolates by detecting the presence of 13 virulence genes using a
      polymerase chain reaction (PCR)-based method. The majority (96 %) of the strains
      contained at least one of the virulence genes. The overall distribution was
      aerA/haem (77 %), alt (53 %), lafA (51 %), ast (39 %), flaA (32 %), aspA (29 %),
      vasH (26 %), ascV (16 %) and aexT (13 %). No amplification products were detected
      for the genes encoding a bundle-forming pilus (BfpA and BfpG) or a Shiga-like
      toxin (stx-1 and stx-2). Five or more virulence genes were detected in 42 % of
      environmental and 24 % of clinical isolates. Among the major species, 48 % of A.
      hydrophila and 42 % of A. dhakensis isolates harboured five or more virulence
      genes compared with 19 % in A. veronii bv. sobria and none in A. caviae isolates.
      Our results suggest that, in Western Australia, strains of A. dhakensis and A.
      hydrophila are potentially more virulent than those of A. veronii bv. sobria and
      A. caviae, although the pathogenic potential of Aeromonas spp. is probably strain
      rather than species-dependent.

PMID- 24859909
TI  - Community structure and coral status across reef fishing intensity gradients in
      Palk Bay reef, southeast coast of India.
AB  - Coral reef fishes are exploited without the knowledge of their sustainability and
      their possible effect in altering the community structure of a coral reef
      ecosystem. Alteration of the community structure could cause a decline in the
      health of coral reefs and its services. We documented the coral community
      structure, status of live corals and reef fish assemblages in Palk Bay at the
      reef fishing hotspots and its nearby reef area with minimum fishing pressure and
      compared it with a control reef area where reef fishing was banned for more than
      two decades. The comparison was based on the percent cover of different forms of
      live corals, their diversity and the density and diversity of reef fishes. The
      reef fish stock in the reef fishing hotspots and its neighbouring reef was lower
      by 61 and 38%, respectively compared to the control reef. The herbivore fish
      Scarus ghobban and Siganus javus were exploited at a rate of 250 and 105 kg
      month(-1) fishermen(-1), respectively, relatively high comparing the small reef
      area. Live and dead corals colonized by turf algae were predominant in both the
      reef fishing hotspots and its nearby coral ecosystems. The percent cover of
      healthy live corals and live corals colonized by turf algae was <10 and >80%,
      respectively, in the intensively fished coral ecosystems. The corals were less
      diverse and the massive Porites and Favia colonies were abundant in the intensive
      reef fishing sites. Results of this study suggest that the impact of reef fish
      exploitation was not solely restricted to the intensively fished reefs, but also
      to the nearby reefs which play a critical role in the resilience of degraded reef
      ecosystems.

PMID- 24859911
TI  - Oscillating high glucose enhances oxidative stress and apoptosis in human
      coronary artery endothelial cells.
AB  - PURPOSE: To investigate the toxic effect of oscillating high glucose (OHG) versus
      persistent high glucose (PHG) in inducing oxidative stress and cellular apoptosis
      in human coronary artery endothelial cells (HCAECs) in vitro. METHODS: HCAECs
      were incubated for 72 h continuously in normal glucose (5.5 mmol/L glucose), PHG
      (25 mmol/L glucose), OHG (5.5 mmol and 25 glucose mmol/L alternating every 6 h)
      and mannitol, respectively. Cellular viability, concentration of oxidative stress
      biomarkers (MDA and GSH) in the supernatants of cell culture, and intracellular
      ROS level were quantitated after exposure to different concentrations of glucose
      for a total 72 h. Apoptosis of HCAECs cultured with various glucose levels was
      evaluated by annexin V-FITC and PI staining followed by analysis with flow
      cytometry. The expressions of HO-1 and Nrf2 were measured by RT-qPCR and Western
      blotting at the end of the experiment. RESULTS: HCAECs cultured with PHG showed
      decreased cellular viability compared to those with normal level of glucose (p <
      0.05). The decrease was more pronounced under OHG condition (p < 0.05). Cellular
      oxidative stress was provoked in HCAECs exposed to PHG with marked increased MDA
      level, reduced GSH concentration and elevated ROS production (p < 0.05). The
      stress was further amplified in the setting of OHG (p < 0.05). The cellular
      apoptosis was enhanced by culturing with PHG, and to a greater extent when
      incubated with OHG. Both expressions of HO-1 and Nrf2 were suppressed in HCAECs
      in persistent hyperglycemia condition, while the inhibition was more intense in
      the fluctuating hyperglycemia condition (p < 0.05). CONCLUSIONS: These findings
      indicate that OHG could be more detrimental to HCAECs than PHG. This is probably
      due to the enhancement of oxidative stress and cellular apoptosis induced by
      frequent glucose swings through the inhibition of Nrf2/HO-1 pathway.

PMID- 24859913
TI  - Fungal accumulation of metals from building materials during brown rot wood
      decay.
AB  - This study analyzes the accumulation and translocation of metal ions in wood
      during the degradation performed by one strain of each of the three brown rot
      fungi; Serpula lacrymans, Meruliporia incrassata and Coniophora puteana. These
      fungi species are inhabitants of the built environment where the prevention and
      understanding of fungal decay is of high priority. This study focuses on the
      influence of various building materials in relation to fungal growth and metal
      uptake. Changes in the concentration of iron, manganese, calcium and copper ions
      in the decayed wood were analyzed by induced coupled plasma spectroscopy and
      related to wood weight loss and oxalic acid accumulation. Metal transport into
      the fungal inoculated wood was found to be dependent on the individual
      strain/species. The S. lacrymans strain caused a significant increase in total
      iron whereas the concentration of copper ions in the wood appeared decreased
      after 10 weeks of decay. Wood inoculated with the M. incrassata isolate showed
      the contrary tendency with high copper accumulation and low iron increase despite
      similar weight losses for the two strains. However, significantly lower oxalic
      acid accumulation was recorded in M. incrassata degraded wood. The addition of a
      building material resulted in increased weight loss in wood degraded by C.
      puteana in the soil-block test; however, this could not be directly linked
      specifically to the accumulation of any of the four metals recorded. The
      accumulation of oxalic acid seemed to influence the iron uptake. The study
      assessing the influence of the presence of soil and glass in the soil-block test
      revealed that soil contributed the majority of the metals for uptake by the fungi
      and contributed to increased weight loss. The varying uptake observed among the
      three brown rot fungi strains toward the four metals analyzed may be related to
      the specific non-enzymatic and enzymatic properties including bio-chelators
      employed by each of the species during wood decay.

PMID- 24859912
TI  - Osteocalcin levels are inversely associated with Hba1c and BMI in adult subjects
      with long-standing type 1 diabetes.
AB  - PURPOSE: Diabetic osteopathy is an upcoming complication of diabetes
      characterized by osteoporosis, increased risk for bone fractures and alterations
      in bone metabolism. Osteocalcin (OC) is a bone-specific protein produced by
      osteoblasts involved in the regulation of glucose and energy metabolism. The aim
      of this study is to determine whether OC serum levels are correlated with
      metabolic control in adult subjects with type one diabetes mellitus (T1DM).
      METHODS: A cross-sectional study was conducted on 93 subjects (51 men) with mean
      age, disease duration and body mass index (BMI) of 39.9 +/- 12.3, 17.2 +/- 12.6
      years and 24.5 +/- 3.4 kg/m(2), respectively. Blood samples were drawn to measure
      levels of hemoglobin A1c (HbA1c), OC, 25-OH vitamin D and PTH. RESULTS:
      Significant inverse correlations were found between OC and HbA1c (r = -0.295, P =
      0.004) and between OC and BMI (r = -0.218, P = 0.037). These correlations were
      confirmed also among men in the analyses by gender [HbA1c vs OC: r = -0.363, P =
      0.009; BMI vs OC: r = -0.291, P = 0.043], and similar but nonsignificant trends
      were confirmed among women. A significant difference in mean OC was also found
      between the lowest and the highest HbA1c tertile (22.3 +/- 10.0 vs 16.9 +/- 8.0
      ng/mL, P = 0.025). CONCLUSIONS: These data show that in T1DM of long duration, OC
      serum levels are inversely associated with HbA1c and BMI, supporting the
      hypothesis that a poor glycemic control can affect osteoblast function.

PMID- 24859914
TI  - Mutational analysis of the (p)ppGpp synthetase activity of the Rel enzyme of
      Mycobacterium tuberculosis.
AB  - Rel(Mtb), a GTP pyrophosphokinase encoded by the Mycobacterium tuberculosis (Mtb)
      genome, catalyzes synthesis of (p)ppGpp from ATP and GDP(GTP) and its hydrolysis
      to GDP(GTP) and pyrophosphate to mediate stringent response, which helps bacteria
      to survive during nutrient limitation. Like other members of Rel_Spo homologs,
      Rel(Mtb) has four distinct domains: HD, Rel_Spo (RSD), TGS and ACT. The N
      terminal HD and RSD are responsible for (p)ppGpp hydrolysis and synthesis,
      respectively. In this study, we have dissected the rel(Mtb) gene function and
      determined the minimal region essential for (p)ppGpp synthetic activity. The
      Rel(Mtb) and its truncated derivatives were expressed from an arabinose inducible
      promoter (P(BAD)), and in vivo functional analyses were done in a (p)ppGpp null
      Escherichia coli strain. Our results indicate that only 243 amino acids (188-430
      residues) containing fragment are sufficient for Rel(Mtb) (p)ppGpp synthetic
      activity. The results were further confirmed by in vitro assays using purified
      proteins. We further characterized the RSD of Rel(Mtb) by substituting several
      conserved amino acids with structurally related residues and identified six such
      residues, which appeared to be critical for maintaining its catalytic activity.
      Furthermore, we have also extended our analysis to an RSD encoding gene rv1366 of
      Mtb, and experimental results indicated that the encoded protein Rv1366 is unable
      to synthesize (p)ppGpp.

PMID- 24859916
TI  - Up for yes.

PMID- 24859915
TI  - Cognitive functioning in men receiving androgen deprivation therapy for prostate
      cancer: a systematic review and meta-analysis.
AB  - PURPOSE: Prior research examining the impact of androgen deprivation therapy
      (ADT) for prostate cancer on cognitive performance has found inconsistent
      relationships. The purpose of this study was to systematically review the
      existing literature and determine the effect of ADT on performance across seven
      cognitive domains using meta-analysis. METHODS: A search of PubMed Medline,
      PsycINFO, Cochrane Library, and Web of Knowledge/Science databases yielded 157
      unique abstracts reviewed by independent pairs of raters. Fourteen studies with a
      total of 417 patients treated with ADT were included in the meta-analysis.
      Objective neuropsychological tests were categorized into seven cognitive domains:
      attention/working memory, executive functioning, language, verbal memory, visual
      memory, visuomotor ability, and visuospatial ability. RESULTS: Separate effect
      sizes were calculated for each cognitive domain using pairwise comparisons of
      patients who received ADT with (1) prostate cancer patient controls, (2)
      noncancer controls, or (3) ADT patients' own pre-ADT baselines. Patients treated
      with ADT performed worse than controls or their own baseline on visuomotor tasks
      (g = -0.67, p = .008; n = 193). The magnitude of the deficits was larger in
      studies with a shorter time to follow-up (p = .04). No significant effect sizes
      were observed for the other six cognitive domains (p = .08-.98). CONCLUSIONS:
      Prostate cancer patients who received ADT performed significantly worse on
      visuomotor tasks compared to noncancer control groups. These findings are
      consistent with the known effects of testosterone on cognitive functioning in
      healthy men. Knowledge of the cognitive effects of ADT may help patients and
      providers better understand the impact of ADT on quality of life.

PMID- 24859918
TI  - Bioinformatics screening regarding herbal components that targetedly regulate the
      function of tumour-associated macrophages.
AB  - As an important component of tumour stroma, tumour-associated macrophages (TAMs)
      promote tumour development and progression. Herbs have been increasingly used in
      anticancer therapies due to their wide-ranging anticancer effects and minor side
      effects. However, no herb-based treatments targeting TAMs have yet been proposed.
      To address this issue, screening using modular analysis bioinformatics techniques
      found 6 core functional modules for TAMs that contain 46 total genes. Moreover,
      15 potential new anticancer drugs that regulate the genes in the 6 core modules
      were identified through bioinformatics techniques and Fisher's exact test. Our
      results provide a new research avenue for targeting TAMs in anticancer therapies.

PMID- 24859919
TI  - Visions for the North Sea: the societal dilemma behind specifying good
      environmental status.
AB  - We augment discussions about the Good Environmental Status of the North Sea by
      developing two extreme visions and assessing their societal benefits. One vision
      ('Then') assumes restoration of benthic functioning; we contend that trawling had
      already degraded the southern North Sea a century ago. Available information is
      used to speculate about benthic functioning in a relatively undisturbed southern
      North Sea. The second vision ('Now') draws on recent benthic functioning. The
      supply of five ecosystem services, supported by benthic functioning, is
      discussed. 'Then' offers confidence in the sustainable supply of diverse services
      but restoration of past function is uncertain and likely to be paired with costs,
      notably trawling restraints. 'Now' delivers known and valued services but
      sustained delivery is threatened by, for example, climate change. We do not
      advocate either vision. Our purpose is to stimulate debate about what society
      wants, and might receive, from the future southern North Sea. 

PMID- 24859920
TI  - First autochthonous familial cluster of invasive community-acquired leukocidin
      positive methicillin-resistant USA300 Staphylococcus aureus in France.
AB  - For the first time, it was reported in France a cluster of autochthonous severe
      community-acquired (CA) infections due to the USA300 methicillin-resistant
      Staphylococcus aureus (MRSA) clone. The three cases belonged to the same family
      without any identified clue of abroad importation pathway. The domestic spread of
      USA300 in France is of concern. 

PMID- 24859921
TI  - A novel derivative of quinazoline, WYK431 induces G2/M phase arrest and apoptosis
      in human gastric cancer BGC823 cells through the PI3K/Akt pathway.
AB  - WYK431, a novel synthetic quinazoline derivative, showing potent inhibition of
      proliferation activity against a broad spectrum of human cancer cell lines. We
      investigated the anticancer effects of WYK431 on BGC823 cells both in vitro and
      in vivo. The results showed that WYK431 inhibited proliferation, arrested the
      cell cycle at the G(2)/M phase, which was related to CDK1 and CDC25C, and induced
      apoptosis associated with activation of caspase-3 and caspase-9 rather than
      caspase-8 in BGC823 cells. Treatment of BGC823 cells with WYK431 resulted in
      upregulation of Bax, release of cytochrome c from the mitochondria to the cytosol
      and disruption of mitochondrial membrane potential. Western blot analysis showed
      that WYK431 downregulated the levels of the PI3K/Akt signaling pathway. Moreover,
      WYK431 effectively suppressed tumor growth in xenograft models in BALB/c athymic
      nude mice without major side action. TUNEL analysis showed that WYK431 induced
      BGC823 cell apoptosis in vivo. Collectively, WYK431 is a novel small molecule
      agent which inhibits BGC823 cell proliferation inducing G(2)/M phase arrest and
      apoptosis via the mitochondrial apoptotic pathway. To assess its potential as a
      promising anticancer agent requires further investigation.

PMID- 24859922
TI  - The Impact of Religious Coping on the Acculturative Stress and Alcohol Use of
      Recent Latino Immigrants.
AB  - Religion plays a prominent role in Latino culture and could be influential during
      difficult life transitions, such as those experienced during the immigration
      process. This study examines relations between religious coping, acculturative
      stress, and alcohol use in a sample of 415 recent Latino immigrants. Higher
      levels of acculturative stress were associated more positive and negative
      religious coping. Positive religious coping was related to lower alcohol use.
      Negative religious coping moderated the relationship between acculturative stress
      and alcohol use. Participants who used more negative religious coping had higher
      rates of alcohol use when experiencing high levels acculturative stress.
      Implications for culturally tailored prevention/interventions are discussed. 

PMID- 24859923
TI  - The role of historical Persian gardens on the health status of contemporary urban
      residents: gardens and health status of contemporary urban residents.
AB  - The inherent economic and social challenges in major cities have been known to
      foster stress among the urban population. Frequent stress over long periods may
      well have serious damaging outcomes, resulting in ailments such as burnout
      syndrome, sleeplessness and exhaustion, depression, feelings of panic, among
      others. Therefore, providing access to resources that may enable people to cope
      with the stress of urban life has become a crucial phenomenon in the twentieth
      century. Increasing empirical evidence indicates that the presence of natural
      areas can contribute to enhancing the quality of life in many ways. This study
      examines two historical Persian gardens from the residents' perspective in well
      known, historic cities of Iran: Isfahan and Kerman. The data were collected
      through questionnaires (n = 252), semi-structured interviews (n = 20), and visual
      observation techniques. The findings demonstrate that nature, diversity and the
      gardens' historical background, and coherence motivate the residents' frequent
      visits to the gardens, which help to address their social, psychological, and
      physical needs. In addition, the residents' involvements and the variety of
      experiences that occur in the gardens lead to the creation of deeper meanings and
      values associated with the gardens. Subsequently, these construct functional and
      emotional attachment that evokes a sense of place and identity and may contribute
      to society's health and well-being.

PMID- 24859924
TI  - Influence of tibial slope on extension and flexion gaps in total knee
      arthroplasty: increasing the tibial slope affects both gaps.
AB  - PURPOSE: Increasing the tibial slope is often performed if the flexion gap is
      narrower than the extension gap. The main hypothesis of this study is that
      increasing the tibial slope coincidentally enlarges the extension gap. METHODS:
      Twenty formalin-fixed cadaveric knees were obtained for study. After CT in full
      extension and 90 degrees  flexion, the data of each specimen were entered into a
      standardized coordinate system and virtual bone cuts were performed with
      incrementally increasing the posterior slope. Gaps were measured at tibiofemoral
      contact points in 90 degrees -flexion and full extension in the medial and
      lateral compartment. RESULTS: Increasing the tibial slope did significantly widen
      both the extension and the flexion gaps (p < 0.001). In extension, the opening
      rates, i.e. the gap increase per degree of slope increase, were equal medially
      and laterally (0.5 mm +/-0.1) medial vs 0.6 mm (+/-0.0) lateral), whereas in
      flexion the lateral gap did open significantly more than the medial one (0.6 mm
      +/-0.1) medial vs 0.9 mm (+/-0.1) lateral (p < 0.001), resulting in a
      significantly greater flexion gap laterally. CONCLUSIONS: Increasing the tibial
      slope beyond the pre-operative planning in order to widen a tight flexion gap
      intra-operatively is not recommended as doing so will increase the extension gap
      simultaneously and will make the medial and lateral flexion gaps unequal.

PMID- 24859925
TI  - A tailored implementation strategy to reduce the duration of intravenous
      antibiotic treatment in community-acquired pneumonia: a controlled before-and
      after study.
AB  - We previously showed that 40 % of clinically stable patients hospitalised for
      community-acquired pneumonia (CAP) are not switched to oral therapy in a timely
      fashion because of physicians' barriers. We aimed to decrease this proportion by
      implementing a novel protocol. In a multi-centre controlled before-and-after
      study, we evaluated the effect of an implementation strategy tailored to
      previously identified barriers to an early switch. In three Dutch hospitals, a
      protocol dictating a timely switch strategy was implemented using educational
      sessions, pocket reminders and active involvement of nursing staff. Primary
      outcomes were the proportion of patients switched timely and the duration of
      intravenous antibiotic therapy. Length of hospital stay (LOS), patient outcome,
      education effects 6 months after implementation and implementation costs were
      secondary outcomes. Statistical analysis was performed using mixed-effects
      models. Prior to implementation, 146 patients were included and, after
      implementation, 213 patients were included. The case mix was comparable. The
      implementation did not change the proportion of patients switched on time (66 %).
      The median duration of intravenous antibiotic administration decreased from 4
      days [interquartile range (IQR) 2-5] to 3 days (IQR 2-4), a decrease of 21 % [95
      % confidence interval (CI) 11 %; 30 %) in the multi-variable analysis. LOS and
      patient outcome were comparable before and after implementation. Forty-three
      percent (56/129) of physicians attended the educational sessions. After 6 months,
      24 % (10/42) of the interviewed attendees remembered the protocol's main message.
      Cumulative implementation costs were <euro>5,798 (<euro>20/reduced intravenous
      treatment day). An implementation strategy tailored to previously identified
      barriers reduced the duration of intravenous antibiotic administration in
      hospitalised CAP patients by 1 day, at minimal cost.

PMID- 24859926
TI  - Heavy metals in jujubes and their potential health risks to the adult consumers
      in Xinjiang province, China.
AB  - The concentrations of seven heavy metals (HMs) in jujube samples collected from
      Hetian region (HTR), Hami region (HMR), Erkesu region (ESR), Bayikuleng region
      (BLR), and Turpan region (TUR) were determined by inductively coupled mass
      spectrometry (ICP-MS). The accuracy and precision of the analytical method were
      confirmed by the certified reference material (GBW 07605). In general, the
      concentration of iron was higher than those of the other six metals in the
      investigated jujube samples. The Hazard Quotient (HQ) and Hazard Index (HI) were
      calculated to evaluate the noncarcinogenic health risk from individual metal and
      combined metals due to the dietary intakes via consumption of jujube. Both HQ and
      HI levels were far below 1, suggesting no noncarcinogenic risks for Xinjiang
      adults under the current consumption rates of the jujubes. Among the jujubes from
      five different regions, BLR jujube had the highest HQ and HI. Fe and As were the
      most concerning HMs in the investigated jujube samples due to their higher
      relative contributions to HIs. 

PMID- 24859927
TI  - Microgrooved Surface Modulates Neuron Differentiation in Human Embryonic Stem
      Cells.
AB  - Stem cell-based therapies have drawn intensive attention in the neuronal
      regenerative fields. Several studies have revealed that stem cells can serve as
      an inexhaustible source for neurons for transplantation therapies. However,
      generation of neurons and directionality has not yet been fully investigated.
      Herein, we investigate the mechanical ramifications of surface topography on
      human embryonic cell differentiation. Microgrooved surfaces with various pitches
      were applied to modulate the neuron differentiation. Our protocol showed that
      neuron differentiation increased as grove pitch decreased. The results indicated
      that 2 MUm microgrooves can improve neuron growth by ~1.7-fold. Our results
      indicate the importance of mechanotransduction on neuronal differentiation and
      highlight the feasibility of manipulating the neuronal differentiation with
      surface topography, providing new perspectives for accommodating clinical
      transplantation. 

PMID- 24859928
TI  - Study of Gap Junctions in Human Embryonic Stem Cells.
AB  - Gap junctional intercellular communication (GJIC) has been described in different
      cell types including stem cells and has been involved in different biological
      events. GJIC is required for mouse embryonic stem cell maintenance and
      proliferation and various studies suggest that functional GJIC is a common
      characteristic of human embryonic stem cells (hESC) maintained in different
      culture conditions. This chapter introduces methods to study gap junctions in
      hESC, from expression of gap junction proteins to functional study of GJIC in
      hESC proliferation, apoptosis, colony growth, and pluripotency. 

PMID- 24859929
TI  - Overexpression of the muscle-specific protein, melusin, protects from cardiac
      ischemia/reperfusion injury.
AB  - Melusin is a muscle-specific protein which interacts with beta1 integrin
      cytoplasmic domain and acts as chaperone protein. Its overexpression induces
      improved resistance to cardiac overload delaying left ventricle dilation and
      reducing the occurrence of heart failure. Here, we investigated possible
      protective effect of melusin overexpression against acute ischemia/reperfusion
      (I/R) injury with or without Postconditioning cardioprotective maneuvers. Melusin
      transgenic (Mel-TG) mice hearts were subjected to 30-min global ischemia followed
      by 60-min reperfusion. Interestingly, infarct size was reduced in Mel-TG mice
      hearts compared to wild-type (WT) hearts (40.3 +/- 3.5 % Mel-TG vs. 59.5 +/- 3.8
      % WT hearts; n = 11 animals/group; P < 0.05). The melusin protective effect was
      also demonstrated by measuring LDH release, which was 50 % lower in Mel-TG
      compared to WT. Mel-TG hearts had a higher baseline level of AKT, ERK1/2 and
      GSK3beta phosphorylation, and displayed increased phospho-kinases level after I/R
      compared to WT mice. Post-ischemic Mel-TG hearts displayed also increased levels
      of the anti-apoptotic factor phospho-BAD. Importantly, pharmacological inhibition
      of PI3K/AKT (Wortmannin) and ERK1/2 (U0126) pathways abrogated the melusin
      protective effect. Notably, HSP90, a chaperone known to protect heart from I/R
      injury, showed high levels of expression in the heart of Mel-TG mice suggesting a
      possible collaboration of this molecule with AKT/ERK/GSK3beta pathways in the
      melusin-induced protection. Postconditioning, known to activate AKT/ERK/GSK3beta
      pathways, significantly reduced IS and LDH release in WT hearts, but had no
      additive protective effects in Mel-TG hearts. These findings implicate melusin as
      an enhancer of AKT and ERK pathways and as a novel player in cardioprotection
      from I/R injury.

PMID- 24859931
TI  - Ketamine does not increase intracranial pressure compared with opioids: meta
      analysis of randomized controlled trials.
AB  - BACKGROUND: Ketamine is traditionally avoided in sedation management of patients
      with risk of intracranial hypertension. However, results from many clinical
      trials contradict this concern. We critically analyzed the published data of the
      effects of ketamine on intracranial pressure (ICP) and other cerebral
      hemodynamics to determine whether ketamine was safe for patients with hemodynamic
      instability and brain injuries. METHODS: We systematically searched the online
      databases of PubMed, Medline, Embase, Current Controlled Trials, and Cochrane
      Central (last search performed on January 15, 2014). Trial characteristics and
      outcomes were independently extracted by two assessors (Xin Wang, Xibing Ding).
      For continuous data, mean differences (MD) were formulated. If the P value of the
      chi-square test was >0.10 or I(2) <50%, a fixed-effects model was used;
      otherwise, the random effects model was adopted. RESULTS: Five trials (n = 198)
      met the inclusion criteria. Using ICP levels within the first 24 h of ketamine
      administration as the main outcome, the use of ketamine leads to the same ICP
      levels as opioids [MD = 1.94; 95% confidence interval (95% CI), -2.35, 6.23; P =
      0.38]. There were no significant differences in mean arterial pressure values
      between the two groups (MD = 0.99; 95% CI, -2.24, 4.22; P = 0.55). Ketamine
      administration was also comparable with opioids in the maintenance of cerebral
      perfusion pressure (MD = -1.07; 95% CI, -7.95, 5.8; P = 0.76). CONCLUSIONS: The
      results of this study suggest that ketamine does not increase ICP compared with
      opioids. Ketamine provides good maintenance of hemodynamic status. Clinical
      application of ketamine should not be discouraged on the basis of ICP-related
      concerns.

PMID- 24859930
TI  - Mitochondrial dysregulation and protection in cisplatin nephrotoxicity.
AB  - Nephrotoxicity is a major side effect of cisplatin in chemotherapy.
      Pathologically, cisplatin nephrotoxicity is characterized by cell injury and
      death in renal tubules. The research in the past decade has gained significant
      understanding of the cellular and molecular mechanisms of tubular cell death,
      revealing a central role of mitochondrial dysregulation. The pathological changes
      in mitochondria in cisplatin nephrotoxicity are mainly triggered by DNA damage
      response, pro-apoptotic protein attack, disruption of mitochondrial dynamics, and
      oxidative stress. As such, inhibitory strategies targeting these cytotoxic events
      may provide renal protection. Nonetheless, ideal approaches for renoprotection
      should not only protect kidneys but also enhance the anticancer efficacy of
      cisplatin in chemotherapy.

PMID- 24859932
TI  - 2'-hydroxyflavanone inhibits prostate tumor growth through inactivation of
      AKT/STAT3 signaling and induction of cell apoptosis.
AB  - Although there have been advances in therapeutic regimes for metastatic
      castration-resistant prostate cancer (CRPC), these recent developments have not
      led to improved cure rates. Thus, more novel agents to prolong patient survival
      are desired. 2'-Hydroxyflavanone (2HF), a nontoxic natural flavonoid, has been
      shown to exhibit pleiotropic anticancer effects in many cancer types, including
      prostate cancer (PCa). However, the therapeutic effects of 2HF on tumor growth
      and its potential mechanisms in CRPC have not been completely elucidated. In the
      present study, utilizing three different metastatic and androgen-independent PCa
      cell models (PC-3, DU145 and C4-2), we found that 2HF treatment not only resulted
      in inhibition of cell proliferation and colony formation in vitro, but also
      delayed subcutaneous tumor growth in vivo. Mechanistically, besides its known
      inhibitory effects on aldo-keto reductase activity and de novo androgen
      synthesis, 2HF also markedly suppressed AKT phosphorylation, signal transducer
      and activator of transcription-3 (STAT3) phosphorylation and transactivation
      subsequently regulating the expression of members of the BCL-2 family (i.e., Mcl
      1, Bcl-2 and Bax) and modulating caspase-mediated cell apoptosis. Overall, this
      study revealed a novel mechanism for 2HF targeting metastatic CRPC, in which
      inactivation of AKT/STAT3 signaling led to cell apoptosis and growth inhibition.

PMID- 24859934
TI  - Laparoscopic narrow-band imaging for the diagnosis of peritoneal metastasis in
      gastric cancer.
AB  - BACKGROUND: Staging laparoscopy (SL) is often used to diagnose peritoneal
      metastasis in patients with advanced gastric cancer, but accurate detection of
      metastasis can be difficult. We evaluated the usefulness of laparoscopic narrow
      band imaging (NBI) versus conventional laparoscopic white-light imaging (WLI) for
      the diagnosis of peritoneal metastasis. METHODS: We excised 37 white nodules from
      the parietal peritoneum of 26 patients with gastric cancer and suspected
      peritoneal metastasis. The WLI and NBI findings were compared with the
      pathological findings. All the peritoneal lesions examined were observed as white
      nodules on WLI. Intranodular vessels were evaluated by WLI and NBI for (1) vessel
      dilatation, (2) vessel tortuousness, (3) vessel heterogeneity, and (4) brown
      spots. RESULTS: Each individual abnormal finding had a diagnostic accuracy of
      less than 79 % with or without NBI. Detection of any one abnormal finding had a
      sensitivity, specificity, and accuracy of 47.8, 85.7, and 62.2 %, respectively,
      on WLI and 91.3, 71.4, and 83.8 %, respectively, on NBI, for detection of
      peritoneal metastasis. Detection of any one abnormal finding on NBI plus clear
      demarcation of the nodule on WLI had a sensitivity of 91.3 %, specificity of 92.9
      %, and accuracy of 91.9 % for detection of peritoneal metastasis. Pathological
      examination showed that a brown spot detected on NBI correlated with dilated
      vessels around cancer cells. Vascular endothelial growth factor was expressed in
      76.2 % of peritoneal metastases. CONCLUSIONS: NBI was more sensitive for the
      detection of dilated vessels than WLI. NBI could be a useful tool for the
      diagnosis of peritoneal metastasis during SL.

PMID- 24859935
TI  - Commentary on the Canadian National Breast Screening study.
AB  - In the setting of the 25-year follow-up of the Canadian National Breast Screening
      Study, the Society of Surgical Oncology continues to endorse mammographic
      screening for women beginning at 40 years of age, while acknowledging that
      mammography has both risks and benefits. Further investigation is warranted to
      develop better screening methods and to determine optimal screening schedules for
      women based on their risk of future breast cancer and their imaging
      characteristics.

PMID- 24859936
TI  - Breast pathology review: does it make a difference?
AB  - BACKGROUND: Breast pathology is a challenging field, and previous work has shown
      discrepancies in diagnoses, even among experts. We set out to determine whether
      mandatory pathology review changes the diagnosis or surgical management of breast
      disease. METHODS: Cases were referred for pathology review after patients
      presented for surgical opinion to the Dubin Breast Center at Mount Sinai Medical
      Center over the course of 2 years. Surgical pathologists with expertise in breast
      disease reviewed slides submitted from the primary institution and rendered a
      second opinion diagnosis. Comparison of these reports was performed for
      evaluation of major changes in diagnosis and definitive surgical management.
      RESULTS: A total of 306 patients with 430 biopsy specimens were reviewed. Change
      in diagnosis was documented in 72 (17 %) of 430 cases and change in surgical
      management in 41 (10 %). A change in diagnosis was more likely to occur in
      patients originally diagnosed with benign rather than malignant disease (31 vs. 7
      %, p < 0.001). Twelve (7 %) of 169 specimens initially diagnosed as benign were
      reclassified as malignant. A malignant diagnosis was changed to benign in 4 (2 %)
      of 261 cases. Change in diagnosis was less common in specimens originating from
      commercial laboratories than community hospitals or university hospitals (8, 19,
      21 %, p = 0.023). Change in management was not dependent on initial institution.
      Type of biopsy specimen (surgical or core) did not influence diagnostic or
      management changes. CONCLUSIONS: We recommend considering breast pathology review
      based on the individual clinical scenario, regardless of initial pathologic
      diagnosis or originating institution.

PMID- 24859937
TI  - Association between palliative resection of the primary tumor and overall
      survival in a population-based cohort of metastatic colorectal cancer patients.
AB  - BACKGROUND: The impact of palliative resection of the primary tumor on outcomes
      in patients with metastatic colorectal cancer (mCRC) remains unclear. The primary
      objective of this study was to evaluate the association between palliative
      resection and overall survival (OS) in a population-based cohort of mCRC.
      METHODS: Patients diagnosed with mCRC between 2006 and 2008 and treated at the BC
      Cancer Agency were reviewed. Survival analysis was conducted using Kaplan-Meier
      methods. Cox proportional hazards regression models were fitted to evaluate the
      relationship between palliative resection and OS while controlling for potential
      confounders, such as age, gender, Eastern Cooperative Oncology Group status,
      carcinoembryonic antigen level, primary tumor location, metastatic site and
      number, and receipt of systemic therapy. To adjust for the heterogeneity and
      selection bias between the group that underwent palliative resection and the
      group that did not, a propensity score-matched analysis was also performed.
      RESULTS: A total of 517 patients were included. Among these cases, 378 (73 %)
      patients underwent palliative resection of their primary tumor, and 139 (27 %)
      patients did not. A total of 327 patients (63 %) were treated with palliative
      chemotherapy. Palliative resection was associated with a longer median OS (17.9
      vs. 7.9 months) and more favorable unadjusted and adjusted hazard ratios (HRs)
      for death (HR 0.46, 95 % CI 0.37-0.56, p < 0.0001 and HR 0.56, 95 % CI 0.40-0.78,
      p = 0.0007, respectively) when compared with no resection. In a propensity score
      matched analysis, prognosis was also more favorable in the resected group (p =
      0.0017). CONCLUSIONS: In this cohort of mCRC patients, palliative resection of
      the primary tumor was associated with improved OS.

PMID- 24859938
TI  - Characterization and treatment of local recurrence following breast conservation
      for ductal carcinoma in situ.
AB  - PURPOSE: The optimal treatment strategy for ductal carcinoma in situ (DCIS)
      continues to evolve and should consider the consequences of initial treatment on
      the likelihood, type, and treatment of recurrences. METHODS: We conducted a
      retrospective cohort study using two data sources of patients who experienced a
      recurrence (DCIS or invasive cancer) following breast-conserving surgery (BCS)
      for index DCIS: patients with an index DCIS diagnosed from 1997 to 2008 at the
      academic institutions of the National Comprehensive Cancer Network (NCCN; N = 88)
      and patients with an index DCIS diagnosed from 1990 to 2001 at community-based
      integrated healthcare delivery sites of the Health Maintenance Organization
      Cancer Research Network (CRN) (N = 182). RESULTS: Just under half of local
      recurrences in both cohorts were invasive cancer. While 40 % of patients in both
      cohorts underwent mastectomy alone at recurrence, treatment of the remaining
      patients varied. In the earlier CRN cohort, most other patients underwent repeat
      BCS (39 %) with only 18 % receiving mastectomy with reconstruction, whereas only
      16 % had repeat BCS and 44 % had mastectomy with reconstruction in the NCCN
      cohort. Compared with patients not treated with radiation, those who received
      radiation for index DCIS were less likely to undergo repeat BCS (NCCN: 6.6 vs. 37
      %, p = 0.001; CRN: 20 vs. 48 %, p = 0.0004) and more likely to experience
      surgical complications after treatment of recurrence (NCCN: 15 vs. 4 %, p = 0.17;
      CRN: 40 vs. 25 %, p = 0.09). CONCLUSION: We found that treatment of recurrences
      after BCS and subsequent complications may be affected by the use of radiotherapy
      for the index DCIS. Initial treatment of DCIS may have long-term implications
      that should be considered.

PMID- 24859939
TI  - Predicting the extent of nodal disease in early-stage breast cancer.
AB  - BACKGROUND: The role of regional nodal ultrasound (US) has been questioned since
      publication of the American College of Surgeons Oncology Group (ACOSOG) Z0011
      data. The goal of this study was to determine if imaging and clinicopathologic
      features could predict the extent of axillary nodal involvement in breast cancer.
      STUDY DESIGN: Patients with T1-T2 tumors who underwent regional nodal US and
      axillary lymph node dissection from 2002 to 2012 were identified from a
      prospective database excluding those who received neoadjuvant chemotherapy.
      Patients whose metastases were identified by US confirmed by needle biopsy were
      compared with those identified by sentinel lymph node dissection (SLND) after a
      negative US. RESULTS: Metastases were identified by US in 190 patients, and by
      SLND in 518 patients. SLND patients had fewer positive nodes (2.2 vs. 4.1; p <
      0.0001), smaller metastases (5.3 vs. 13.8 mm; p < 0.0001), and a lower incidence
      of extranodal extension (24 vs. 53 %; p < 0.0001) than the US group. Even when US
      identified <=2 abnormal nodes, patients were still more likely to have >=3
      positive nodes (45 %) than SLND patients (19 %; p < 0.001). After adjusting for
      tumor size, receptor status, and histology, multivariate analysis revealed that
      metastases identified by US [odds ratio (OR) 4.01; 95 % confidence interval (CI)
      2.75-5.84] and lobular histology (OR 1.77; 95 % CI 1.06-2.95) predicted having
      >=3 positive nodes. CONCLUSIONS: Imaging and clinicopathologic features can be
      used to predict the extent of nodal involvement. Patients with US-detected
      metastases, even if small volume, have a higher burden of nodal involvement than
      patients with SLND-detected metastases and may not be comparable with patients in
      the ACOSOG Z0011 trial.

PMID- 24859940
TI  - Does high flexion after total knee replacement really improve our patients'
      quality of life at a short-term follow-up? : a comparative case-control study
      with hyperflex PFC Sigma versus a Triathlon knee series.
AB  - PURPOSE: A full range of motion after total knee arthroplasty has become more and
      more requested by our patients, leading to novel designs of knee implants, the so
      called "hyperflex" knees. The aim of the present study was to confirm whether or
      not hyperflexion of operated knees really improves the patients' quality of life.
      METHODS: A retrospective comparative case-control study has been carried out to
      compare clinical results shown in two types of knee prosthesis, from two
      homogeneous paired groups of patients including 45 cases of a "hyperflex" model
      (RP-F), while the control group consisted of 43 cases of a "regular design" model
      (Triathlon) in terms of expected postoperative flexion. RESULTS: The hyperflex
      group demonstrated significant higher mean values of passive flexion at 119.9
      degrees  in the RP-F group versus 111.1 degrees  in the Triathlon group. However,
      global results in the "regular" control group were significantly better than the
      "hyperflex" study group, in both IKS knee and functional scores at 84.4 points
      (RP-F) vs. 89.8 points (Triathlon), and 84.6 points (RP-F) vs. 89.5 points
      (Triathlon), respectively. Moreover, the self-administered KOOS questionnaire was
      significantly in favor of the control group, with 73.5 points in RP-F knees
      versus 86.0 points for Triathlon knees at global KOOS postoperative scores.
      CONCLUSION: The quality of life of operated patients after TKA obviously would be
      considered as the main priority, which was better obtained by a "regular design"
      in our study. Hence "high flexion" cannot be considered as an absolute target
      when choosing a model for total knee arthroplasty.

PMID- 24859941
TI  - Ischio-pubic stress fracture after peri-acetabular osteotomy in patients with hip
      dysplasia.
AB  - PURPOSE: Ischio-pubic stress fracture is one of the potential complications after
      peri-acetabular osteotomy (PAO) in patients with hip dysplasia. The purpose of
      this study was to examine the prevalence of and risk factors for ischio-pubic
      fractures following PAO. METHODS: A total of 296 hips in 275 patients who
      underwent transposition osteotomy of the acetabulum between 2001 and 2012 were
      retrospectively reviewed. Patient characteristics and radiographic parameters
      were compared between patients with and without fracture. RESULTS: Fourteen
      ipsilateral hips (4.7%) in 14 female patients had fracture of the inferior pubic
      ramus (11 hips) or the ischial ramus (three hips) on the same side as the surgery
      at an average of 4.6 weeks after PAO. Multivariate analysis indicated that
      younger age at operation (odds ratio of 1.43 per five years, p = 0.0169) and
      greater degree of correction (odds ratio of 1.98 per five degrees, p = 0.0005)
      were significantly associated with ischio-pubic fracture as independent risk
      factors. All fractures healed conservatively with partial weight-bearing.
      CONCLUSIONS: Younger female patients and greater deformity corrections increased
      the risk of ischio-pubic stress fracture after PAO.

PMID- 24859943
TI  - [Reappraisal of reconstruction technique after total gastrectomy for gastric
      cancer].
AB  - Recently, total gastrectomy has been increasingly used for gastric cancer.
      However, it remains controversial as to the optimal technique for reconstruction
      after total gastrectomy. As of now, more than 70 reconstruction techniques
      following total gastrectomy have been reported, and each model has its own merits
      and demerits. Currently no ideal digestive reconstruction exists. The cores of
      these controversies are how to improve the postoperative quality of life on the
      basis of oncological and operative safety. The controversies focus on the
      following three aspects: (1) necessity of physiological duodenal passage; (2)
      necessity of a gastric pouch; (3) the optimal pouch configuration. Evidence-based
      medicine with large sample, multicentric, prospective randomized control trials
      is warranted.

PMID- 24859944
TI  - [Selection and techniques of digestive tract reconstruction after laparoscopic
      total gastrectomy].
AB  - In recent years, laparoscopic total gastrectomy is gradually increasing for
      gastric cancer. Digestive tract reconstruction after laparoscopic total
      gastrectomy is one of the difficult problems for laparoscopic surgeons and the
      keys to success. Therefore, exploring an ideal method of digestive tract
      reconstruction is an important subject for clinical treatment. Reasonable choice
      and techniques of digestive tract reconstruction after laparoscopic total
      gastrectomy are summarized and evaluated in this article. 

PMID- 24859942
TI  - Genetic 135G/C polymorphism of RAD51 gene and risk of cancer: a meta-analysis of
      28,956 cases and 28,372 controls.
AB  - The RAD51 gene is essential for the repair of damaged DNA related to tumor
      development. Although a number of genetic studies have attempted to link the
      135G/C polymorphism of RAD51 gene to the risk of cancer, the results were
      inconclusive. The present study aimed at investigating the pooled association
      using the more comprehensive meta-analysis. The PubMed, EBSCO, and BIOSIS
      databases were searched to identify eligible studies which were published in
      English before March 2014. Data were extracted using standardized methods. The
      association was assessed by odds ratio (OR) with 95 % confidence interval (CI).
      Begg's test was used to measure publication bias. Sensitivity analyses were also
      performed to assess the stability of the results. A total of 45 eligible studies
      with 28,956 patients and 28,372 controls were included in this meta-analysis.
      Overall, significant association was detected between 135G/C polymorphism and
      increased cancer risk (C allele vs. G allele: OR 1.23, 95 % CI 1.18-1.28; CC vs.
      GG: OR 2.41, 95 % CI 2.12-2.74; CC vs. CG: OR 3.86, 95 % CI 3.41-4.37; recessive
      model: OR 3.57, 95 % CI 3.19-4.00). In further stratified analysis, significantly
      elevated cancer risk was observed among Caucasians but not Asians. Subgroup
      analysis by different cancers also showed their significant associations in
      breast cancer, hematologic malignances, ovarian cancer, colorectal cancer and
      endometrial cancer, but not in head and neck cancer. Our results indicated that
      the RAD51 135G/C polymorphism was a candidate for susceptibility of cancer. The
      effect of the variants on the expression levels and the possible functional role
      of the variants in different cancers should be addressed in further studies.

PMID- 24859945
TI  - [Reconstruction of digestive tract after distal gastrectomy].
AB  - There are various types of digestive tract reconstruction techniques after distal
      gastrectomy. Among them, Billroth I and II are still the predominant option in
      China at present. In recent years, Roux-en-Y configuration, jejunal
      interposition, J-pouch interposition (JPI), double-tract reconstruction, pylorus
      preserving method, and laparoscopic reconstruction and anastomosis techniques
      have gained more attention in recent years. Although there is no universal and
      explicit guideline, the current consensus is that the reconstruction style should
      be adopted by the principles of digestive tract reconstruction, based on
      patient's condition, socioeconomic status and surgeon's experience.

PMID- 24859946
TI  - [Different methods of alimentary tract reconstruction after proximal
      gastrectomy].
AB  - Selection of the ideal technique for alimentary tract reconstruction after
      gastrointestinal surgery has been a major concern for surgeons. Although various
      reconstruction methods are available after gastrectomy, there are obvious
      differences between proximal gastrectomy and other procedures because of its
      characteristics in anatomy and physiology. It is an important way to make an
      individualized and feasible scheme for reconstruction in order to improve
      patient's quality of life. 

PMID- 24859947
TI  - [Reconstruction of pancreatic enteric anastomosis after pancreaticoduodenectomy].
AB  - Pancreatic enteric anastomosis is an important step during
      pancreaticoduodenectomy. Based on the anastomosis site, pancreatic enteric
      anastomosis is classified as pancreaticojejunostomy anastomosis and
      pancreaticogastrostomy. Depending on the jejunum site, reconstruction can be
      perform as end-to-end or end-to-side anastomosis. Previous randomized clinical
      trials, showed no significant differences between pancreaticojejunostomy and
      pancreaticogastrostomy. Binding pancreaticojejunostomy and binding
      pancreaticogastrostomy are easy to perform. The rate of pancreatic leakage is
      related to the texture of the pancreas and the size of the pancreatic duct. It is
      helpful to reduce pancreatic leakage by placing a pancreatic duct stent. The
      simple and effective pancreatic enteric reconstruction is the future direction
      for minimizing leakage.

PMID- 24859948
TI  - [Application and evaluation of pouch configuration in rectal surgery].
AB  - Colonic pouch can improve fecal continence after low anterior resection in the
      short-term, but its superiority would disappear in the long-term (2 years after
      surgery), since fecal continence improves gradually with time in the non-pouch
      group. Furthermore, the incidence of incomplete defecation increases gradually
      with time, and a lot of patients would have difficulty in defecation and require
      long-term use of suppositories and enemas. Pouch enforcement will result in
      prolonged operation time and increased treatment cost. Therefore, the value of
      colonic pouch in low rectal anastomosis is being questioned, and its application
      diminishes gradually. For patients with ulcerative colitis (UC) or familial
      adenomatous polyposis (FAP) after total colectomy, ileal pouch anal anastomosis
      (IPAA) can reduce fecal frequency and improve patients' quality of life in both
      short-term and long-term, by increasing the volume of the neo-rectum and altering
      intestinal motility. For these reasons, IPAA is the first surgical choice for UC
      and FAP.

PMID- 24859949
TI  - [Evaluation of reconstruction technique after esophagectomy for esophageal
      cancer].
AB  - Surgery remains the cornerstone of treatment for esophageal cancer, although
      improvements have been made in surgical maneuvers and perioperative care, serious
      complications still occur after operation. The reconstruction of alimentary tract
      is a key procedure to ensure success of operation, it is related to perioperative
      complication and prognosis. Selection of procedure should be individualized based
      on the stage and location of the disease, medical condition and the surgeon's
      experience. 

PMID- 24859950
TI  - [Feasibility of delta-shaped gastroduodenostomy in totally laparoscopic distal
      gastrectomy for gastric cancer].
AB  - OBJECTIVE: To investigate the feasibility of delta-shaped (DS) gastroduodenostomy
      in totally laparoscopic distal gastrectomy (TLDG) for gastric cancer. METHODS:
      From July 2013 to November 2013, 22 gastric cancer patients underwent DS
      gastroduodenostomy using laparoscopic linear stapler. All the patients underwent
      TLDG with D2 lymphadenectomy. In addition, modified DS anastomosis (when closing
      the common entry hole, previous duodenal staple line was also removed) was used
      in selected patients. Clinical data of these 22 patients were retrospectively
      analyzed. RESULTS: All the patients underwent TLDG with D2 lymphadenectomy and DS
      gastroduodenostomy. Among them, 12 patients underwent modified DS anastomosis.
      The total operative time was (194.6+/-38.4) min, and the DS anastomosis time was
      (19.1+/-14.1) min. The number of linear stapler cartridges used per patient was
      5.8+/-0.8. The intraoperative blood loss was (49.5+/-24.0) ml. The number of
      lymph nodes harvested per patient was 32.8+/-12.4. All the patients achieved
      microscopic cancer-free resection margin. The time to the first postoperative
      flatus, first water intake, and semi-liquid diet was (2.9+/-0.7) d, (4.8+/-1.1)
      d, and (6.6+/-1.2) d, respectively. The duration of postoperative hospital stay
      was (10.1+/-2.3) d. The postoperative complication rate was 9.1% (2/22). No
      patients developed anastomosis-related complications including anastomotic
      leakage, stenosis, or bleeding. CONCLUSIONS: Delta-shaped gastroduodenostomy is
      simple, easy, safe, and feasible. It will be an ideal choice for reconstruction
      after totally laparoscopic distal gastrectomy, and has great value in clinical
      practice.

PMID- 24859951
TI  - [Comparison of short- and long-term efficacy of three procedures in postoperative
      digestive tract reconstruction for upper gastric cancer].
AB  - OBJECTIVE: To compare the short- and long-term efficacy of three different
      procedures used for digestive tract reconstruction after radical gastrectomy for
      upper gastric cancer. METHODS: Clinical data of 191 patients with upper gastric
      cancer undergoing radical gastrectomy in the Fujian Provincial Hospital between
      January 2000 and December 2012 were analyzed retrospectively. Surgical procedures
      were classified as total gastrectomy followed by Roux-en-Y esophagojejunostomy
      (TG-RY, n=123), proximal gastrectomy followed by esophagogastrostomy (PG-EG,
      n=40), and proximal gastrectomy followed by jejunal interposition (PG-JI, n=28).
      Clinicopathological characteristics, perioperative and long-term outcomes were
      compared among the three groups. RESULTS: The operative time was shorter (178 vs.
      248 and 224 min, P<0.05), and the intraoperative blood loss was less (194 vs. 323
      and 265 ml, P<0.05) in PG-EG group than those in TG-RY and PG-JI groups. Early
      postoperative complications and hospital stay were comparable (both P>0.05). With
      respect to gastrectomy-associated symptoms, reflux and heartburn were more
      frequent in PG-EG patients, while dumpling syndrome was more frequent after TG
      RY. Postoperative weight loss was not significantly different among three
      procedures (P>0.05), however, hemoglobin and serum albumin levels were lower in
      TG-RY patients (both P<0.05). The 5-year survival rate was similar (P>0.05).
      CONCLUSIONS: Surgeons need to choose the proper procedure according to tumor
      features and patient condition. PG-JI should be the first choice in terms of
      fewer complaints and better nutrition. TG-RY tends to be used for larger and more
      advanced tumors. PG-EG is the most minimally invasive procedure and thus may be
      suitable for older and high-risk patients.

PMID- 24859952
TI  - [Comparison of long-term outcomes between Billroth-I and Roux-en-Y reconstruction
      after distal gastrectomy].
AB  - OBJECTIVE: To compare the long-term outcomes of Billroth-I and Roux-en-Y
      reconstruction after distal gastrectomy. METHODS: Clinical data of 151 patients
      with gastric cancer undergoing distal gastrectomy in the Affiliated Oncologic
      Hospital of Guangzhou Medical University between June 2000 and June 2010 were
      analyzed retrospectively. Reconstruction was performed with Billroth-I in 87
      patients (B-I group) and Roux-en-Y in 64 (R-Y group). All the patients were
      followed up for at least 3 years. Three years after operation, clinical symptoms,
      endoscopic findings, nutritional status, gallstone formation, and late
      gastrointestinal complications were compared between the two groups. RESULTS:
      Three years after operation, gastroesophageal reflux symptoms were found in 10
      patients (11.5%) in B-I group and in 3 (4.7%) in R-Y group, and dumping syndrome
      was diagnosed in 8 patients (9.2%) in B-I group and in 3 (4.7%) in R-Y group, but
      the differences between the two groups were not statistically significant (both
      P>0.05). Endoscopic examination showed that the amount of residue in the gastric
      stump, remnant gastritis-reflux esophagitis, and bile reflux in R-Y group were
      better as compared to B-I group (all P<0.05). Body weight, serum albumin level,
      and total cholesterol level were similar in the two groups (all P>0.05). The
      incidences of gallstone formation and late gastrointestinal complications did not
      differ between B-I group and R-Y group (13.2% vs. 15.8%, and 8.0% vs. 4.7%
      respectively, both P>0.05). CONCLUSION: As compared with Billroth-I, Roux-en-Y is
      associated with better long-term outcomes in terms of less remnant gastritis
      reflux esophagitis and less bile reflux into the gastric remnant.

PMID- 24859953
TI  - [Outcomes after surgery for refractory constipation patients complicated with
      megacolon].
AB  - OBJECTIVE: To explore the efficacy of different procedures for refractory
      constipation complicated with megacolon. METHODS: Clinical data of 112 patients
      of refractory constipation complicated with megacolon undergoing surgery in our
      institute from June 2007 to January 2013 were retrospectively analyzed. Of these
      112 patients, the duration of constipation ranged from 4 to 22 years. Seventy
      four patients had previous abdominal operations. Surgical procedures: (1)Jinling
      procedure (subtotal colectomy plus ascending colorectal posterior wall side-to
      side anastomosis, n=81), including 24 laparoscopy-assisted procedures, 18
      terminal ileostomies. (2)total colectomy plus ileorectal side-to-side
      anastomosis(n=18). (3)total colectomy plus end ileostomy, and ileorectal
      posterior wall side-to-side anastomosis 6 months later(n=13). The end ileostomy
      was reversed 6 months after operation. RESULTS: The successful rate was 100%, and
      no surgery-related deaths were found. Postoperative complications included early
      diarrhea (90 cases, 80.4%), anal pain and incomplete evacuation (22 cases,
      19.6%), urinary retention within 24-48 h after catheter removal (16 cases,
      14.2%), anastomosis bleeding (9 cases, 8.0%), anastomosis leakage (6 cases,
      5.4%), and intestinal obstruction (15 cases, 13.4%). Six patients with intestinal
      obstruction underwent adhesiolysis, and others were managed by conservative
      therapy. At the postoperative follow-up at 6 months, the Wexner constipation
      score was significantly reduced (5.8-8.3 vs. 21.4-28.7, P<0.01), and malnutrition
      improved as well. CONCLUSION: Surgical intervention results in good efficacy for
      refractory constipation complicated with megacolon.

PMID- 24859954
TI  - [Application of subserosal injection of carbon nanoparticles via infusion needle
      to label lymph nodes in laparoscopic radical gastrectomy].
AB  - OBJECTIVE: To explore the feasibility of subserosal injection of carbon
      nanoparticle via venous infusion needle to label lymph node and its application
      value in laparoscopic radical gastrectomy. METHODS: Forty patients with gastric
      cancer were randomly divided into two groups (carbon nanoparticle group and
      control group). Subserosal injection of carbon nanoparticle around the tumor was
      performed via venous infusion needle laparoscopically at the beginning of surgery
      in carbon nanoparticles group, while the patients routinely underwent
      laparoscopic radical gastrectomy in control group. Results of harvested lymph
      nodes were compared between the two groups. The perioperative complications and
      the side effect of carbon nanoparticle were also evaluated. RESULTS: The average
      number of harvested lymph node in carbon nanoparticle group (31.7+/-7.6) was
      significantly higher than that in control group (19.8+/-6.1, P<0.05). The
      proportion of harvested small node (< 5 mm) in carbon nanoparticles group(61.0%)
      was higher than that in control group(43.3%, P<0.01). The mean harvest time in
      carbon nanoparticle group [(23.5+/-4.8) min] was shorter than that in control
      group [(32.6+/-5.5) min, P<0.05]. The rate of black-dyed harvested lymph node was
      61.9% and the metastasis rate of black-dyed lymph node was 23.0% in carbon
      nanoparticle group, which were significantly higher than those without black
      dyed(6.2%, P<0.05) and those in control group (15.7%, P<0.05). The operative time
      and perioperative complications were not significantly different between the two
      groups, and no serious side effect caused by carbon nanoparticle was observed.
      CONCLUSION: Subserosal injection of carbon nanoparticle via venous infusion
      needle to label lymph nodes during laparoscopic radical gastrectomy is safe and
      feasible. It can increase the number of harvested lymph node, especially the
      small node.

PMID- 24859955
TI  - [Comparative study on da Vince robotic and laparoscopic radical gastrectomy for
      gastric cancer].
AB  - OBJECTIVE: To compare the short-term clinical outcomes of laparoscopic and da
      Vince robotic radical gastrectomy for gastric cancer and evaluate the safety and
      efficacy of robotic system. METHODS: Clinical data of 200 consecutive gastric
      cancer patients undergoing radical gastrectomy, including 100 cases of robotic
      (RRG group) and 100 cases of laparoscopic (LRG group), in our department from
      January 2012 to May 2013 were retrospectively analyzed. Reconstruction of the
      alimentary tract was achieved using extracorporeal method through a
      minilaparotomy in LRG group, and intracorporeal robot-sewn anastomosis in RRG
      group. Comparative analysis between the two groups for intraoperative factors
      (conversion, blood loss, operative time, incision length), oncologic outcomes
      (TMN stage, lymph node dissection, margin) and postoperative parameters
      (ventilation time, hospital stay, complications, mortality) was performed.
      RESULT: There was only 1 conversion in LRG group. As compared to LRG group, RRG
      group was associated with less blood loss[(60+/-16) vs. (98+/-17) ml, P=0.005],
      longer operative time [(215+/-46) vs. (188+/-52) min, P=0.001], shorter incision
      length [(4.2+/-1.7) vs. (8.9+/-2.6) cm, P=0.028], and shorter postoperative
      hospital stay [(4.5+/-2.6) vs. (5.7+/-3.1) d, P=0.018] in RRG group. While there
      were no significant differences in other aspects between the two groups, such as
      number of harvested lymph nodes, distance to upper or lower margin of tumor,
      postoperative bowel function recovery, and postoperative complication morbidity.
      CONCLUSION: Robotic radical gastrectomy is feasible and safe for gastric cancer,
      and has better short-term and oncologic outcomes compared with laparoscopic
      radical gastrectomy.

PMID- 24859956
TI  - [Comparative study of outcomes after laparoscopic versus open
      pancreaticoduodenectomy].
AB  - OBJECTIVE: To investigate the surgical and oncological outcomes after
      laparoscopic pancreaticoduodenectomy (LPD), and compare its efficacy with open
      pancreaticoduodenectomy (OPD). METHODS: Clinical data of 40 patients with
      malignant tumor undergoing pancreaticoduodenectomy between January 2012 and
      January 2013 in our department were retrospectively analyzed. Patients were
      divided into LPD and OPD group according to operative procedure. Operative time,
      blood loss, harvested lymph nodes, drainage on first postoperative day (POD1),
      first flatus day, time to liquid diet, postoperative period of fever,
      postoperative hospital stay, postoperative complications, and 1-year cumulative
      survival rate and recurrence rate were compared between the two groups. RESULTS:
      There were no significant differences between the two groups in operative time,
      harvested lymph nodes, TNM stages, postoperative period of fever, time to drain
      removal, postoperative complications, 1-year cumulative survival rate and
      recurrence rate (all P>0.05). As compared to OPD group, LPD group showed less
      blood loss [(168.2+/-87.4) ml vs.(353.5+/-140.1) ml, P<0.001], drainage on POD1
      [(157.7+/-69.7) ml vs. (289.1+/-197.0) ml, P=0.039], earlier flatus [(4.1+/-0.9)
      d vs. (6.6+/-3.4) d, P=0.024], shorter time to liquid diet [(5.8+/-1.3) d vs.
      (8.2+/-3.5) d, P=0.040], earlier ambulation [(3.6+/-1.4) d vs.(6.2+/-1.5) d,
      P<0.001], and shorter postoperative hospital stay [(17.0+/-2.2) d vs.(25.7+/
      13.8) d, P=0.047]. CONCLUSION: LPD confers similar surgical and oncological
      outcomes and is superior to OPD in terms of decreased blood loss and rapid
      postoperative recovery.

PMID- 24859957
TI  - [Continuous negative pressure-flush through extraperitoneal dual tube in the
      treatment and prevention for rectal cancer patients with anastomotic leakage
      after low anterior resection].
AB  - OBJECTIVE: To compare the efficacy between continuous negative pressure-flush
      through extraperitoneal dual tube and conventional drainage in the treatment and
      prevention for anastomotic leakage after low anterior resection in patients with
      rectal cancer. METHODS: Clinical data of 627 rectal cancer patients undergoing
      low anterior resection by the same surgical team from January 2007 to March 2012
      were reviewed retrospectively. Of 627 patients, 370 received self-made easy
      extraperitoneal dual tube which was placed in the dorsal site of an anastomosis
      for drainage (dual tube group), and the other 257 received conventional drainage
      tube from abdominal cavity (convention group) prophylactically. The incidence of
      postoperative anastomotic leakage, reoperation rate, drainage tube indwelling
      duration, hospitalization duration, hospitalization expense, quality of life
      score, incidence of anastomotic stricture within 6 months after operation were
      compared between the two groups. RESULTS: Anastomotic leakage after low Dixon
      operation was found in 25 cases (4.0%, 25/627), including 14 cases (3.8%, 14/370)
      in dual tube group, and 11 cases (4.3%, 11/257) in convention group, and the
      difference was not statistically significant. After anastomotic leakage
      occurrence, all the patients in dual tube group were managed by continuous
      negative pressure (50 mmHg)-flush through another self-made easy intra-rectal
      dual tube without reoperation, while 5 patients in conventional group underwent
      operation again because of treatment failure with continuous negative pressure
      flush through intra-rectal dual tube for half a month. Drainage tube indwelling
      duration was (9.7+/-2.7) d and (16.4+/-3.6) d, hospitalization duration was
      (15.7+/-4.3) d and (21.5+/-6.4) d, hospitalization expenses was (42 470+/-3190)
      Yuan and (53 480+/-5630) Yuan in dual tube group and conventional group
      respectively, the differences were all statistically significant (all P<0.05).
      Quality of life on the 15th day of anastomotic leakage treatment was
      significantly better in dual tube group as compared to conventional group
      (P<0.05). CONCLUSION: Though continuous negative pressure-flush through
      extraperitoneal dual tube can not decrease the incidence of anastomotic leakage
      in rectal cancer patients after low anterior resection, it may increase the
      successful rate of conservative therapy, decrease the reoperation rate, and
      improve the quality of life when combined with the use of an intra-rectal dual
      tube.

PMID- 24859958
TI  - [Transanal endoscopic microsurgery by transanal glove port combined with
      colonoscopy for excision of rectal tumors].
AB  - OBJECTIVE: To evaluate the feasibility and efficacy of transanal endoscopic
      microsurgery (TEM) by transanal glove port combined with colonoscopy for excision
      of rectal tumors. METHODS: Eight patients with rectal cancer eligible for local
      resection were chosen to receive a procedure performed via a "glove TEM port"
      from October 2012 to March 2013. This device was constructed on-table using a
      circular anal dilator (CAD), standard surgical glove, colonoscopy instruments and
      straight laparoscopic instruments. RESULTS: Procedures of all the patients were
      completed successfully by glove TEM. The median (range) diameter of tumor was
      2.6(1.5-3.5) cm, the median (range) operative time was 55.6(30-110) min.
      Postoperative pathology included villous adenomas (n=3), tubular adenomas (n=2),
      tubulovillous adenomas (n=2), serrated adenoma (n=1), low-grade intraepithelial
      neoplasia (n=2), and high-grade intraepithelial neoplasia (n=1). All resection
      margins were negative. Two patients presented with postoperative minor bleeding.
      There were no serious intraoperative complications. No cancer recurrence was
      found during a follow-up of 1-5 (median 3.1) months. CONCLUSION: Transanal
      endoscopic microsurgery by transanal glove port combined with colonoscopy in the
      treatment of early rectal cancer is easy and safe.

PMID- 24859959
TI  - [Efficacy evaluation of laparoscopy-assisted surgery for Siewert I adenocarcinoma
      of the esophagogastric junction].
AB  - OBJECTIVE: To evaluate the safety and efficacy of laparoscopy-assisted surgery
      for Siewert I adenocarcinoma of the esophagogastric junction (AEJ). METHODS:
      Clinical data of 36 patients who underwent left transthoracic dissection of lower
      mediastinal lymph node followed by laparoscopy D2 lymph node dissection for
      Siewert I AEJ in the Fujian Provincial Cancer Hospital between March 2008 and
      March 2013 were analyzed retrospectively. A left thoracic-abdominal single
      incision was used without transection of costal arch. Celiac lymph nodes
      dissection was performed laparoscopically followed by left transthoracic
      dissection of lower mediastinal lymph node. Digestive tract reconstruction was
      carried out by esophagus-gastric posterior wall end-to-side anastomosis. RESULTS:
      Laparoscopy-assisted surgery was successfully achieved in all the 36 patients and
      there were no in-hospital deaths. The mean operation time, blood loss and number
      of harvested lymph node were (216.4+/-46.0) min, (252.1+/-41.1) ml and 30.7+/-3.2
      respectively. All the procedures were R0 resections. The complication rate was
      16.7% (6/36). All the complications were managed by conservative treatment, and
      there were no re-operations. The lymphatic metastasis rate was 50.0% (18/36), and
      the lymph node groups with high metastatic rate (all >10.0%) were groups 1, 2, 3,
      7, 9, 110 and 111. The median follow-up was 25 months. The overall 3-year
      survival was 48.0%. CONCLUSION: Laparoscopy-assisted surgery for Siewert I AEJ is
      safe and feasible.

PMID- 24859960
TI  - [Medial approach versus lateral approach in laparoscopic colorectal resection: a
      meta-analysis].
AB  - OBJECTIVE: To compare the safety and efficacy of the medial approach(MA) and the
      lateral approach (LA) in the treatment of colorectal disease. METHODS: Studies
      published from January 1994 to April 2013 that compared MA to LA in laparoscopic
      colorectal resection were collected. Publications in English were mainly
      identified from Medline, Embase, Cochrane Library, and those in Chinese from
      Wanfang database and CNKI database. Conversion rate, operative time, blood loss,
      number of harvested lymph nodes, hospital stay, complication, mortality,
      recurrence, and hospitalization costs of MA and LA were meta-analyzed using fixed
      effect and random-effect models. RESULTS: Five cohort studies (2 randomized
      controlled trials and 3 retrospective studies) including 881 patients were
      enrolled and analyzed. Of these patients, 416 and 465 underwent laparoscopic
      colorectal resection with MA and LA respectively. As compared to LA, MA had
      significantly lower conversion rate (OR=0.42, 95%CI:0.25-0.72, P=0.001), shorter
      operative time (WMD=-52.62, 95%CI:-63.23--42.01, P<0.01), less number of
      harvested lymph nodes (WMD=-1.17, 95%CI:-1.89--0.45, P=0.001), while blood loss
      was less and hospitalization cost lower. Significant differences in
      intraoperative complications and postoperative complications were not found
      between the two group (OR:0.57, 95%CI:0.15-2.18, P=0.41; OR:0.78, 95%CI:0.52
      1.17, P=0.23). CONCLUSIONS: Compared with LA, MA has the advantages of shorter
      operative time and lower conversion rate with similar safety. Differences in
      blood loss, hospitalization cost and oncological safety between the two
      approaches warrant further investigation.

PMID- 24859961
TI  - [Experiences of scarless laparoscopic radical resection of rectal cancer].
AB  - OBJECTIVE: To explore the feasibility and safety of scarless laparoscopic radical
      resection of rectal cancer. METHODS: Clinical data of 26 patients who underwent
      scarless laparoscopic radical resection of rectal cancer from January 2011 to
      June 2013 were retrospectively analyzed. Lymph node dissection and transection of
      proximal and distal colon were performed in the conventional manner of total
      mesorectal excision (TME). The distal rectum 2 cm away from the tumor was closed
      with a linear stapler, and was pulled out through the anus. The specimen was
      extracted through the Alexis. The rectal opening was reclosed with a linear
      stapler. End-to-end colorectal anastomosis was performed using the double
      stapling technique. RESULTS: The operation time was (126+/-35) min. The
      intraoperative blood loss was (33+/-61) ml. The number of harvested lymph nodes
      was 17.0+/-5.6. The time to first bowel movement was (2.7+/-1.3) d. The
      postoperative hospital stay was (7.9+/-2.6) d. Only one case developed
      anastomotic hemorrhage. CONCLUSION: Scarless laparoscopic radical resection of
      rectal cancer is feasible.

PMID- 24859962
TI  - [Promotion of postoperative recovery with fast track surgery for gastric cancer
      patients undergoing gastrectomy: a prospective randomized controlled study].
AB  - OBJECTIVE: To study the safety and feasibility of fast track surgery (FTS) in the
      promotion of postoperative recovery for gastric cancer patients undergoing
      gastrectomy. METHODS: From January to December in 2013, 71 gastric cancer
      patients were prospectively enrolled and randomized into the FTS group and the
      control group. Patient in the FTS group received FTS management and those in the
      control group received routine management. The postoperative recovery and stress
      were compared between the two groups. RESULTS: FTS was associated with shorter
      time to bowel function return [(67.8+/-19.7) h vs. (90.0+/-20.6) h, P<0.01],
      shorter hospital stay [(13.5+/-3.0) d vs. (17.8+/-7.3) d, P=0.01], lower hospital
      cost [(23.8+/-3.7) thousand Yuan vs. (27.8+/-6.1) thousand Yuan, P<0.05], and
      less stress response (lower pain score, WBC count, C-reactive protein, all
      P<0.01). The postoperative complications including ileus, infection, anastomotic
      leakage were similar (all P>0.05). CONCLUSION: Fast track surgery decreases
      postoperative stress response and promotes recovery.

PMID- 24859963
TI  - [Analysis of 19 cases undergoing reoperation for complications following
      esophagectomy].
AB  - OBJECTIVE: To investigate the cause and the management of treatment and
      prevention of reoperation following esophagectomy. METHODS: Clinical data of 946
      cases with esophageal cancer undergoing esophagectomy from January 2000 to
      December 2012 by the same surgical team in the Beijing Cancer Hospital were
      retrospectively analyzed. Among them, 19 patients underwent reoperation after
      esophagectomy because of serious complications. Clinical features and treatment
      course of these 19 cases were summarized. RESULTS: The indications and procedures
      of reoperation included thoracotomy for hemorrhage (n=4), diaphragmatic hernia
      repair (n=4), thoracic duct ligation for chylothorax (n= 4), re-suturing for
      incision dehiscence (n=4), re-laparotomy and re-thoracotomy for drainage of
      traumatic pancreatitis (n=1), re-laparotomy for intestinal obstruction (n=1), and
      tracheotomy for bilateral recurrent laryngeal nerve paralysis (n=1). All the 19
      patients were successfully cured without perioperative deaths and further
      complications. CONCLUSIONS: The indications of reoperation following
      esophagectomy include postoperative bleeding, diaphragmatic hernia, chylothorax
      and abdominal incision dehiscence.

PMID- 24859964
TI  - [Expression and significance of miR-125a and Mcl-1 in intestinal tissue after
      massive small bowel resection in rat].
AB  - OBJECTIVE: To investigate the expression and significance of miR-125a and anti
      apoptotic protein Mcl-1 in intestinal tissue after massive small bowel resection
      in intestinal adaptation. METHODS: Sprague-Dawley rats (54 male rats, 8-week old)
      were divided into 3 groups randomly, including two control groups. Rats in the
      experiment group were subjected to 70% massive small bowel resection. Rats in the
      resection group underwent simple intestinal resection and anastomosis. Rats in
      the control group underwent laparotomy alone. A 5 cm intestine approximately 1 cm
      distal to the anastomosis was harvested a week after operation. Expression of Mcl
      1 was assessed by immunohistochemistry and real-time PCR was used to detect the
      expression of miR-125a in intestinal tissue. RESULTS: The positive expression of
      Mcl-1 in the experiment group was 18.8%(3/16), significantly lower than that in
      the control group(76.5%, 13/17) and the resection group (83.33%, 15/18)(both
      P<0.01). The expression of miR-125a in the experiment group was 1.92,
      significantly higher than that in the control group (1.01) and the resection
      group (1.05)(both P<0.01). CONCLUSION: miR-125a and anti-apoptotic protein Mcl-1
      may play an important role in intestinal adaptation process and they may regulate
      each other through a certain pathway.

PMID- 24859965
TI  - [Application value of magnetic compression anastomosis in digestive tract
      reconstruction].
AB  - Magnetic compression anastomosis can compress tissues together and restore the
      continuity. Magnetic compression anastomosis mainly experienced three stages:
      magnetic ring, magnetic ring and column, and smart self-assembling magnets for
      endoscopy (SAMSEN). Nowadays, the magnetic compression anastomosis has been
      applied in vascular and different digestive tract surgeries, especially for
      complex surgery, such as anastomotic stenosis of biliary ducts after liver
      transplantation or congenital esophageal stenosis. Although only case reports are
      available at present, the advantages of the magnetic compression anastomosis
      includes lower cost, simplicity, individualization, good efficacy, safety, and
      minimally invasiveness. We are building a better technical platform to make
      magnetic compression anastomosis more advanced and popularized. 

PMID- 24859966
TI  - [Step-up strategy for diagnosis and treatment of acute superior mesenteric venous
      thrombosis].
AB  - Acute superior mesenteric venous thrombosis is rare. With advance in CT
      venography, angiography and diagnostic laparoscopy, the incidence of acute
      superior mesenteric venous thrombosis has increased worldwide with more access to
      early diagnosis. The use of anticoagulation medication, interventional radiology,
      and damage control approach has resulted in better clinical outcomes. At present,
      the new step-up approach for acute superior mesenteric venous thrombosis includes
      CT venography as the main diagnostic technique, anticoagulation as the
      cornerstone of therapy, local transcatheter thrombolytic therapy as the key
      recanalization method, and adjunctive use of arterial spasmolysis and various
      endovascular manipulation and damage control surgery by intestinal resection plus
      jejunostomy and ileostomy or open abdomen. This strategy may further improve
      clinical outcomes. This review will present the most recent advance in this
      strategy.

PMID- 24859967
TI  - Chromatin regulates DNA torsional energy via topoisomerase II-mediated relaxation
      of positive supercoils.
AB  - Eukaryotic topoisomerases I (topo I) and II (topo II) relax the positive (+) and
      negative (-) DNA torsional stress (TS) generated ahead and behind the
      transcription machinery. It is unknown how this DNA relaxation activity is
      regulated and whether (+) and (-)TS are reduced at similar rates. Here, we used
      yeast circular minichromosomes to conduct the first comparative analysis of topo
      I and topo II activities in relaxing chromatin under (+) and (-)TS. We observed
      that, while topo I relaxed (+) and (-)TS with similar efficiency, topo II was
      more proficient and relaxed (+)TS more quickly than (-)TS. Accordingly, we found
      that the relaxation rate of (+)TS by endogenous topoisomerases largely surpassed
      that of (-)TS. We propose a model of how distinct conformations of chromatin
      under (+) and (-)TS may produce this unbalanced relaxation of DNA. We postulate
      that, while quick relaxation of (+)TS may facilitate the progression of RNA and
      DNA polymerases, slow relaxation of (-)TS may serve to favor DNA unwinding and
      other structural transitions at specific regions often required for genomic
      transactions. 

PMID- 24859968
TI  - The autophagy/lysosome pathway is impaired in SCA7 patients and SCA7 knock-in
      mice.
AB  - There is still no treatment for polyglutamine disorders, but clearance of mutant
      proteins might represent a potential therapeutic strategy. Autophagy, the major
      pathway for organelle and protein turnover, has been implicated in these
      diseases. To determine whether the autophagy/lysosome system contributes to the
      pathogenesis of spinocerebellar ataxia type 7 (SCA7), caused by expansion of a
      polyglutamine tract in the ataxin-7 protein, we looked for biochemical,
      histological and transcriptomic abnormalities in components of the
      autophagy/lysosome pathway in a knock-in mouse model of the disease, postmortem
      brain and peripheral blood mononuclear cells (PBMC) from patients. In the mouse
      model, mutant ataxin-7 accumulated in inclusions immunoreactive for the autophagy
      associated proteins mTOR, beclin-1, p62 and ubiquitin. Atypical accumulations of
      the autophagosome/lysosome markers LC3, LAMP-1, LAMP2 and cathepsin-D were also
      found in the cerebellum of the SCA7 knock-in mice. In patients, abnormal
      accumulations of autophagy markers were detected in the cerebellum and cerebral
      cortex of patients, but not in the striatum that is spared in SCA7, suggesting
      that autophagy might be impaired by the selective accumulation of mutant ataxin
      7. In vitro studies demonstrated that the autophagic flux was impaired in cells
      overexpressing full-length mutant ataxin-7. Interestingly, the expression of the
      early autophagy-associated gene ATG12 was increased in PBMC from SCA7 patients in
      correlation with disease severity. These results provide evidence that the
      autophagy/lysosome pathway is impaired in neurons undergoing degeneration in
      SCA7. Autophagy/lysosome-associated molecules might, therefore, be useful markers
      for monitoring the effects of potential therapeutic approaches using modulators
      of autophagy in SCA7 and other autophagy/lysosome-associated neurodegenerative
      disorders. 

PMID- 24859969
TI  - RANK receptor oligomerisation in the regulation of NFkappaB signalling.
AB  - The interaction of receptor activator of NFkappaB (RANK), a member of the tumour
      necrosis factor receptor superfamily, with RANK ligand is crucial for the
      formation, function and survival of osteoclasts. The role of the cytoplasmic
      oligomerisation domain (pre-ligand assembly domain; PLAD or 'IVVY' motif) in the
      ligand-dependent activation of downstream NFkappaB signalling has not been
      studied previously. The discovery of truncating mutations of TNFRSF11A (W434X and
      G280X that lack the PLAD) as the cause of rare cases of osteoclast-poor
      osteopetrosis offered the opportunity for functional study of this region.
      Recapitulating the W434X mutation by transcription activator-like effector
      nuclease (TALEN)-mediated targeted disruption of Tnfrsf11a within the region
      homologous to W434X in the mouse macrophage-like cell line RAW264.7 impaired
      formation of osteoclast-like cells. Using overexpression studies, we demonstrated
      that, in contrast to WT-RANK, the absence of the PLAD in G280X-RANK and W434X
      RANK prevented ligand-independent but not ligand-dependent oligomerisation. Cells
      expressing W434X-RANK, in which only two of the three TRAF6-binding motifs are
      present, continued to exhibit ligand-dependent NFkappaB signalling. Hence, the
      absence of the PLAD did not prevent ligand-induced trimerisation and subsequent
      NFkappaB activation of RANK, demonstrating that therapeutic targeting of the PLAD
      in the prevention of osteoporosis may not be as effective as proposed previously.

PMID- 24859970
TI  - LKB1 signalling attenuates early events of adipogenesis and responds to
      adipogenic cues.
AB  - cAMP-response element-binding protein (CREB) is required for the induction of
      adipogenic transcription factors such as CCAAT/enhancer-binding proteins
      (C/EBPs). Interestingly, it is known from studies in other tissues that LKB1 and
      its substrates AMP-activated protein kinase (AMPK) and salt-inducible kinases
      (SIKs) negatively regulate gene expression by phosphorylating the CREB co
      activator CRTC2 and class IIa histone deacetylases (HDACs), which results in
      their exclusion from the nucleus where they co-activate or inhibit their targets.
      In this study, we show that AMPK/SIK signalling is acutely attenuated during
      adipogenic differentiation of 3T3-L1 preadipocytes, which coincides with the
      dephosphorylation and nuclear translocation of CRTC2 and HDAC4. When subjected to
      differentiation, 3T3-L1 preadipocytes in which the expression of LKB1 was stably
      reduced using shRNA (Lkb1-shRNA), as well as Lkb1-knockout mouse embryonic
      fibroblasts (Lkb1(-/-) MEFs), differentiated more readily into adipocyte-like
      cells and accumulated more triglycerides compared with scrambled-shRNA-expressing
      3T3-L1 cells or Wt MEFs. In addition, the phosphorylation of CRTC2 and HDAC4 was
      reduced, and the mRNA expression of adipogenic transcription factors Cebpa,
      peroxisome proliferator-activated receptor gamma (Pparg) and adipocyte-specific
      proteins such as hormone-sensitive lipase (HSL), fatty acid synthase (FAS), aP2,
      GLUT4 and adiponectin was increased in the absence of LKB1. The mRNA and protein
      expression of Ddit3/CHOP10, a dominant-negative member of the C/EBP family, was
      reduced in Lkb1-shRNA-expressing cells, providing a potential mechanism for the
      up-regulation of Pparg and Cebpa expression. These results support the hypothesis
      that LKB1 signalling keeps preadipocytes in their non-differentiated form. 

PMID- 24859971
TI  - Screening of critical genes in lung adenocarcinoma via network analysis of gene
      expression profile.
AB  - Biomarker discovery is of great importance in diagnosis and treatment of
      diseases. In present study, a number of differentially expressed genes (DEGs)
      were identified for lung adenocarcinoma via comparative analysis of gene
      expression data. A gene expression core signature was generated for four types of
      lung adenocarcinoma (EGFR-mutated, KRAS-mutated, ALK-mutated and triple-negative
      adenocarcinoma). Functional enrichment analysis with DAVID tools revealed that up
      regulated genes were mainly associated with cell cycle while down-regulated genes
      were mainly involved in vasculature development and cell adhesion. Then it was
      used to retrieve relevant small molecule drugs with Connectivity map and
      trichostatin A was predicted to be the top candidate drug for treatment of lung
      cancer. Network clustering was performed with MCL in cytoscape to identify sub
      networks and several hub genes were obtained: CDC25C, ICT1, TK1 and EZH2. These
      genes play important roles in the progression of lung cancer and some have been
      suggested as potential biomarkers. Therefore, our findings are beneficial in
      deepening the understandings about the pathogenesis and providing directions for
      future researches.

PMID- 24859972
TI  - Elevated proinflammatory cytokine IL-17A in the adjacent tissues along the
      adenoma-carcinoma sequence.
AB  - Considerable evidence has suggested that chronic inflammation is a causative
      factor in the development of human colorectal cancer (CRC). Interleukin (IL)-17A
      produced mainly by Th17 cells is a novel proinflammatory cytokine and increased
      IL-17A is associated with colorectal neoplastic transformation. In this study, we
      have evaluated the expression of IL-17A in the adjacent tissues along the
      colorectal adenoma-carcinoma sequence. The expression of IL-17A in the adjacent
      tissues of colorectal adenoma (adenoma-adjacent, n = 32) and sporadic CRC (CRC
      adjacent, n = 45) was examined. In addition, the expression pattern of Th17 cell
      differentiation stimulators (IL-1beta, IL-6 and IL-23A) in the adjacent tissues
      were also examined. The results showed that the expression level of IL-17A mRNA
      was non-statistically increased (4-fold higher) in the adenoma-adjacent tissues
      and it became significantly increased (9-fold higher) in the CRC-adjacent tissues
      as compared with the control. The expression level of IL-17A in the CRC-adjacent
      tissues was not associated with CRC clinicopathological parameters and overall
      survival. Immunohistochemistry confirmed an increased density of intraepithelial
      IL-17A expressing cells in the CRC-adjacent tissues. The Th17 cell
      differentiation simulators IL-1beta and IL-6 were also shown in an increase trend
      from the adenoma-adjacent to CRC-adjacent tissues. These results provide evidence
      that IL-17A/Th17 response is enhanced in the adjacent tissues during the
      colorectal neoplastic transformation.

PMID- 24859973
TI  - Different methods of pretreatment Ki-67 labeling index evaluation in core
      biopsies of breast cancer patients treated with neoadjuvant chemotherapy and
      their relation to response to therapy.
AB  - Increased proliferation activity of breast cancer cells evaluated by Ki-67
      immunohistochemistry, i.e. a high Ki-67 labeling index (Ki-67 LI), may predict
      better tumor regression in case of neoadjuvant chemotherapy. Despite
      recommendations for the evaluation of Ki-67 LI, there are variations in
      methodology. We assessed the effect of different evaluation methods on the Ki-67
      LI in patients with different response to neoadjuvant chemotherapy. Thirty
      pretreatment core-biopsy samples of patients receiving neoadjuvant docetaxel
      epirubicin chemotherapy with or without capecitabine were evaluated for their Ki
      67 LI. Pathologic regression was categorized as no regression, partial regression
      and complete regression, with 10 cases in each category. Three antibodies (MIB1,
      B56, SP6), 4 observers and 4 methods (counting or estimating on glass slides and
      counting or estimating on representative digital images) were compared. The
      Kruskal-Wallis test and analyses of variance were performed to investigate the
      differences in Ki-67 LIs between different clinical outcomes (tumor regression
      categories). Breast carcinomas with pathological complete regression had a higher
      mean Ki-67 LI than tumors not achieving complete regression with any methods,
      observers and antibodies investigated, although there was a variation between
      different evaluations in what may represent high proliferation. Estimating the Ki
      67 LI on digital images representing the highest proliferation in the core biopsy
      seemed the best in separating complete responders from non-responders. High Ki-67
      LI values were more likely associated with pathological complete regression
      independently of the method of evaluation used, although the definition of high
      proliferation is problematic. Estimating the Ki-67 LI may be an adequate method
      of evaluation. 

PMID- 24859974
TI  - Transcriptional activation of PIK3R1 by PPARgamma in adipocytes.
AB  - Phosphatidylinositol 3-kinase (PI3K) plays an important role in the metabolic
      actions of insulin and is required for adipogenesis. Regulatory subunit 1 of PI3K
      (PIK3R1) is a critical component of the PI3K signaling pathway. Peroxisome
      proliferator-activated receptor gamma (PPARgamma) is a key regulator of
      adipogenesis. Although the PPARgamma agonist rosiglitazone induces the expression
      of PIK3R1, the transcriptional regulation of PIK3R1 in adipocytes remains
      unknown. In this study, we investigated whether PIK3R1 is a direct target of
      PPARgamma. The level of PIK3R1 expression in 3T3-L1 cells was increased after the
      induction of adipocyte differentiation and was also induced by overexpression of
      PPARgamma. Furthermore, the upregulation of PPARgamma-mediated PIK3R1 expression
      enhanced the insulin-stimulated AKT activation in 3T3-L1 cells. Two putative
      peroxisome proliferator response elements (PPREs) in the PIK3R1 promoter were
      identified as PPARgamma binding sites. By chromatin immunoprecipitation, we
      observed that PPARgamma interacts with the two PPRE regions of the PIK3R1
      promoter in mature adipocytes. In addition, luciferase reporter assays showed
      that the -1183/-1161 and -573/-551 regions of the PIK3R1 promoter contain
      essential elements for PPARgamma binding. Taken together, these results suggest
      that PPARgamma is essential for the transcriptional activity of PIK3R1 during
      adipogenesis. 

PMID- 24859975
TI  - Apple ring rot-responsive putative microRNAs revealed by high-throughput
      sequencing in Malus * domestica Borkh.
AB  - MicroRNAs (miRNAs) are small non-coding RNAs, which silence target mRNA via
      cleavage or translational inhibition to function in regulating gene expression.
      MiRNAs act as important regulators of plant development and stress response. For
      understanding the role of miRNAs responsive to apple ring rot stress, we
      identified disease-responsive miRNAs using high-throughput sequencing in Malus *
      domestica Borkh.. Four small RNA libraries were constructed from two control
      strains in M. domestica, crabapple (CKHu) and Fuji Naga-fu No. 6 (CKFu), and two
      disease stress strains, crabapple (DSHu) and Fuji Naga-fu No. 6 (DSFu). A total
      of 59 miRNA families were identified and five miRNAs might be responsive to apple
      ring rot infection and validated via qRT-PCR. Furthermore, we predicted 76 target
      genes which were regulated by conserved miRNAs potentially. Our study
      demonstrated that miRNAs was responsive to apple ring rot infection and may have
      important implications on apple disease resistance.

PMID- 24859976
TI  - A murrel interferon regulatory factor-1: molecular characterization, gene
      expression and cell protection activity.
AB  - In this study, we have reported a first murrel interferon regulatory factor-1
      (designated as Murrel IRF-1) which is identified from a constructed cDNA library
      of striped murrel Channa striatus. The identified sequence was obtained by
      internal sequencing method from the library. The Murrel IRF-1 varies in size of
      the polypeptide from the earlier reported fish IRF-1. It contains a DNA binding
      domain along with a tryptophan pentad repeats, a nuclear localization signal and
      a transactivation domain. The homologous analysis showed that the Murrel IRF-1
      had a significant sequence similarity with other known fish IRF-1 groups. The
      phylogenetic analysis exhibited that the Murrel IRF-1 clustered together with IRF
      1 members, but the other members including IRF-2, 3, 4, 5, 6, 7, 8, 9 and 10 were
      clustered individually. The secondary structure of Murrel IRF-1 contains 27%
      alpha-helices (85 aa residues), 5.7% beta-sheets (19 aa residues) and 67.19%
      random coils (210 aa residues). Furthermore, we predicted a tertiary structure of
      Murrel IRF-1 using I-Tasser program and analyzed the structure on PyMol surface
      view. The RNA structure of the Murrel IRF-1 along with its minimum free energy (
      284.43 kcal/mol) was also predicted. The highest gene expression was observed in
      spleen and its expression was inducted with pathogenic microbes which cause
      epizootic ulcerative syndrome in murrels such as fungus, Aphanomyces invadans and
      bacteria, Aeromonas hydrophila, and poly I:C, a viral RNA analog. The results of
      cell protection assay suggested that the Murrel IRF-1 regulates the early defense
      response in C. striatus. Moreover, it showed Murrel IRF-1 as a potential
      candidate which can be developed as a therapeutic agent to control microbial
      infections in striped murrel. Overall, these results indicate the immune
      importance of IRF-1, however, the interferon signaling mechanism in murrels upon
      infection is yet to be studied at proteomic level.

PMID- 24859979
TI  - Fishermen's profits maximization: case of generalized Nash equilibrium of a non
      symmetrical game.
AB  - In the present paper, we consider a bio-economic equilibrium model which
      describes the dynamics of a fish population fished by several fishermen seeking
      to maximize their profits. Each fisherman tries to find the fishing effort which
      maximizes his profit at biological equilibrium without any consultation with
      others, but all of them have to respect two constraints: (1) the sustainable
      management of the resources ; and (2) the preservation of the biodiversity. With
      all these considerations, our problem leads to a generalized Nash equilibrium
      problem. The objective is to show that even when a fisherman (i) provides a
      fishing effort equal to twice the fishing effort of a fisherman (j), then the
      profit of fisherman (i) is not necessarily double that of fisherman (j).

PMID- 24859977
TI  - The grapevine basic helix-loop-helix (bHLH) transcription factor positively
      modulates CBF-pathway and confers tolerance to cold-stress in Arabidopsis.
AB  - Basic helix-loop-helix (bHLH)-type transcription factors play diverse roles in
      plant physiological response and stress-adaptive regulation network. Here, we
      identified one grapevine bHLH transcription factor from a cold-tolerant accession
      'Heilongjiang seedling' of Chinese wild Vitis amurensis (VabHLH1) as a
      transcriptional activator involved in cold stress. We also compared with its
      counterpart from a cold-sensitive Vitis vinifera cv. Cabernet Sauvignon
      (VvbHLH1). These two putative proteins are characterized by the presence of the
      identically conserved regions of 54 amino acid residues of bHLH signature domain,
      and shared 99.1% amino acid identity, whereas several stress-related cis
      regulatory elements located in both promoter regions differed in types and
      positions. Expressions of two bHLHs in grapevine leaves were induced by cold
      stress, but evidently differ between two grapevine genotypes upon cold exposure.
      Two grapevine bHLH proteins were exclusively localized to the nucleus and
      exhibited strong transcriptional activation activities in yeast cells.
      Overexpression of either VabHLH1 or VvbHLH1 transcription factor did not affect
      the growth and development of transgenic Arabidopsis plants, but enhanced
      tolerance to cold stress. The improved tolerance in VabHLH1- or VvbHLH1
      overexpressing Arabidopsis plants is associated with multiple physiological and
      biochemical changes that occurred during the time-course cold stress. These most
      common changes include the evaluated levels of proline, decreased amounts of
      malondialdehyde and reduced membrane injury as reflected by electrolyte leakage.
      VabHLH1 and VvbHLH1 displayed overlapping, but not identical, roles in activating
      the corresponding CBF cold signaling pathway, especially in regulating the
      expression of CBF3 and RD29A. Our findings demonstrated that two grapevine bHLHs
      act as positive regulators of the cold stress response, modulating the level of
      COR gene expression, which in turn confer tolerance to cold stress.

PMID- 24859978
TI  - Molecular cloning and differential expression in tissues of a tyrosinase gene in
      the Pacific oyster Crassostrea gigas.
AB  - Tyrosinases are a group of type-3 copper proteins that catalyze the first two
      reactions in the melanin biosynthesis in organisms ranging from bacteria, fungi,
      plants to animals. Tyrosinases are not only involved in pigmentation, but also
      play an important role in the innate immunity in invertebrates. Additionally,
      tyrosinases are also known to be involved in the biogenesis and pigmentation of
      shells. The recently published Crassostrea gigas genome sequences revealed that
      the Pacific oyster possesses at least 26 tyrosinase isoforms. However, their
      molecular features are largely understudied. In fact, the full-length mRNA
      sequence was determined for one of the tyrosinase genes (i.e., CgTry1; aka cgi
      tyr1). Here we report the full-length transcript of a second C. gigas tyrosinase
      (CgTyr2) sequence and the determination of its sequence features characteristic
      to the tyrosinase family proteins. We also showed that CgTyr2 gene was
      differentially expressed with the highest level of expression in mantle edges,
      suggesting its potential role in the formation of periostracum/pigmentation. Our
      comprehensive phylogenetic reconstructions supported that hemocyanins possibly
      evolved from a tyrosinase by an ancient gene duplication followed by functional
      differentiation, and the current large number of tyrosinase isoforms in C. gigas
      and other mollusks were originated from multiple gene duplication events that
      took places before and after mollusk species were established. 

PMID- 24859980
TI  - ESHRE Task Force on Ethics and Law 21: genetic screening of gamete donors:
      ethical issues.
AB  - This Task Force document explores the ethical issues involved in the debate about
      the scope of genetic screening of gamete donors. Calls for expanded donor
      screening arise against the background of both occasional findings of serious but
      rare genetic conditions in donors or donor offspring that were not detected
      through present screening procedures and the advent of new genomic technologies
      promising affordable testing of donors for a wide range of conditions. Ethical
      principles require that all stakeholders' interests are taken into account,
      including those of candidate donors. The message of the profession should be that
      avoiding all risks is impossible and that testing should remain proportional.

PMID- 24859982
TI  - The effect of smoking on rotator cuff and glenoid labrum surgery: a systematic
      review.
AB  - BACKGROUND: Several orthopaedic conditions have been reported to be adversely
      affected by smoking. Only a few studies have looked at outcomes related to
      smoking in shoulder surgery. PURPOSE/HYPOTHESIS: To determine whether smoking has
      a negative influence on tendinous, ligamentous, and cartilaginous shoulder
      surgery. The hypothesis was that smoking has a negative influence from both a
      basic science and clinical outcomes perspective on soft tissue shoulder surgery.
      STUDY DESIGN: Systematic review. METHODS: A systematic review of multiple medical
      databases was performed evaluating clinical outcomes and basic science studies to
      determine the effects of smoking on tendinous, ligamentous, and cartilaginous
      shoulder surgery. The search strategy was based on "shoulder AND [smoke OR
      smoking OR nicotine OR tobacco]." English language clinical outcomes or basic
      science studies following soft tissue surgery of the shoulder were included.
      Studies excluded consisted of those with evidence level 5, partial or total
      shoulder arthroplasty, fracture reduction and fixation, oncologic mass excision,
      and osteotomy around the shoulder. RESULTS: Ten studies were identified for
      inclusion and analysis. Eight of these studies, which included 1 basic science
      study, investigated the relationship between smoking and outcomes of rotator cuff
      repair (RCR), and 2 examined the effects of smoking on outcomes of glenoid labrum
      repair. No studies were found that specifically explored the effects of smoking
      on cartilaginous shoulder surgery. The basic science study and 3 of the 7
      clinical outcomes studies investigating smoking and rotator cuff (RTC) surgery
      outcomes found a statistically significant negative association resulting in
      decreased RTC tendon repair quality, decreased biomechanics, poorer clinical
      outcomes, and impaired healing of small-medium RTC tears as assessed by magnetic
      resonance imaging. In addition, 1 of 2 clinical outcomes studies examining
      smoking and glenoid labrum repair reported an increased need for surgical
      revision of superior labral anterior to posterior (SLAP) tears in smokers. No
      basic science studies were found that investigated the effects of smoking on
      glenoid labrum surgery. CONCLUSION: Smoking has a negative influence on RCR
      clinical outcomes and is associated with decreased healing of small-medium RTC
      tears after repair. The current literature suggests a negative influence of
      nicotine and smoking on RCR from both a basic science and clinical outcomes
      perspective. Smoking cessation would benefit patients undergoing RCR and improve
      clinical outcomes. The relationship of smoking and labral/SLAP repair or
      articular cartilage is less clear. Further research is needed to evaluate
      associations with these surgeries and outcomes. CLINICAL RELEVANCE: Smoking has a
      negative influence on RCR clinical outcomes and is associated with decreased
      healing of small-medium RTC tears after repair.

PMID- 24859983
TI  - Australian doctors' leader attacks plan to charge to see a GP.

PMID- 24859984
TI  - GPs vote against charging patients for their services.

PMID- 24859981
TI  - Targeted gene therapy and cell reprogramming in Fanconi anemia.
AB  - Gene targeting is progressively becoming a realistic therapeutic alternative in
      clinics. It is unknown, however, whether this technology will be suitable for the
      treatment of DNA repair deficiency syndromes such as Fanconi anemia (FA), with
      defects in homology-directed DNA repair. In this study, we used zinc finger
      nucleases and integrase-defective lentiviral vectors to demonstrate for the first
      time that FANCA can be efficiently and specifically targeted into the AAVS1 safe
      harbor locus in fibroblasts from FA-A patients. Strikingly, up to 40% of FA
      fibroblasts showed gene targeting 42 days after gene editing. Given the low
      number of hematopoietic precursors in the bone marrow of FA patients, gene-edited
      FA fibroblasts were then reprogrammed and re-differentiated toward the
      hematopoietic lineage. Analyses of gene-edited FA-iPSCs confirmed the specific
      integration of FANCA in the AAVS1 locus in all tested clones. Moreover, the
      hematopoietic differentiation of these iPSCs efficiently generated disease-free
      hematopoietic progenitors. Taken together, our results demonstrate for the first
      time the feasibility of correcting the phenotype of a DNA repair deficiency
      syndrome using gene-targeting and cell reprogramming strategies.

PMID- 24859985
TI  - Quebec to pass bill on physician assisted suicide.

PMID- 24859986
TI  - GPs urge government to create a national self care strategy.

PMID- 24859988
TI  - Human seminal fluid as a source of prostate cancer-specific microRNA biomarkers.

PMID- 24859989
TI  - The social network of PELP1 and its implications in breast and prostate cancers.
AB  - Proline, glutamic acid- and leucine-rich protein 1 (PELP1) is a multi-domain
      scaffold protein that serves as a platform for various protein-protein
      interactions between steroid receptors (SRs) and signaling factors and cell
      cycle, transcriptional, cytoskeletal, and epigenetic remodelers. PELP1 is known
      to be a coregulator of transcription and participates in the nuclear and
      extranuclear functions of SRs, ribosome biogenesis, and cell cycle progression.
      The expression and localization of PELP1 are dysregulated in hormonal cancers
      including breast and prostate cancers. This review focuses on the interactive
      functions and therapeutic and prognostic significance of PELP1 in breast and
      prostate cancers.

PMID- 24859992
TI  - The results of pollicization for congenital thumb hypoplasia.
AB  - We assessed pollicizations performed by one surgeon; compared function of the
      pollicized digit in patients with and without forearm/wrist anomalies; and
      determined if hand function changed with age. A total of 42 hands were assessed
      an average of 5.7 years post-operatively, 21 with a forearm/wrist anomaly (Group
      1) and 21 without (Group 2). Fourteen patients with 16 pollicizations were
      assessed on two occasions 3.5 years apart. Carpometacarpal joint motion was near
      normal in both groups (decreased retropulsion in Group 1). Metacarpophalangeal
      and interphalangeal joint flexion, grip, thumb lateral and tip pinch strengths,
      and Jebsen timed test were superior in Group 2. Subjective assessment by
      patients/parents found 72% excellent/good results for function and 94% for
      appearance. Doctor excellent/good assessments were 60% and 70%, respectively.
      Forearm/wrist anomalies significantly compromised results but are not a
      contraindication for pollicization. Strength and Jebsen timed test measurements
      improved at the second assessment of 16 thumbs, but this was consistent with age
      related improvement. LEVEL OF EVIDENCE 4. 

PMID- 24859987
TI  - Peripheral changes in endometriosis-associated pain.
AB  - BACKGROUND: Pain remains the cardinal symptom of endometriosis. However, to date,
      the underlying mechanisms are still only poorly understood. Increasing evidence
      points towards a close interaction between peripheral nerves, the peritoneal
      environment and the central nervous system in pain generation and processing.
      Recently, studies demonstrating nerve fibres and neurotrophic and angiogenic
      factors in endometriotic lesions and their vicinity have led to increased
      interest in peripheral changes in endometriosis-associated pain. This review
      focuses on the origin and function of these nerves and factors as well as
      possible peripheral mechanisms that may contribute to the generation and
      modulation of pain in women with endometriosis. METHODS: We conducted a
      systematic search using several databases (PubMed, MEDLINE, EMBASE and CINAHL) of
      publications from January 1977 to October 2013 to evaluate the possible roles of
      the peripheral nervous system in endometriosis pathophysiology and how it can
      contribute to endometriosis-associated pain. RESULTS: Endometriotic lesions and
      peritoneal fluid from women with endometriosis had pronounced neuroangiogenic
      properties with increased expression of new nerve fibres, a shift in the
      distribution of sensory and autonomic fibres in some locations, and up-regulation
      of several neurotrophins. In women suffering from deep infiltrating endometriosis
      and bowel endometriosis, in which the anatomical distribution of lesions is
      generally more closely related to pelvic pain symptoms, endometriotic lesions and
      surrounding tissues present higher nerve fibre densities compared with peritoneal
      lesions and endometriomas. More data are needed to fully confirm a direct
      correlation between fibre density in these locations and the amount of perceived
      pain. A better correlation between the presence of nerve fibres and pain symptoms
      seems to exist for eutopic endometrium. However, this appears not to be exclusive
      to endometriosis. No correlation between elevated neurotrophin levels and pain
      severity appears to exist, suggesting the involvement of other mediators in the
      modulation of pain. CONCLUSIONS: The increased expression of neurotrophic factors
      and nerve fibres in endometriotic lesions, eutopic endometrium and the peritoneum
      imply a role of such peripheral changes in the pathogenesis of endometriosis
      associated pain. However, a clear link between these findings and pain in
      patients with endometriosis has so far not been demonstrated.

PMID- 24859993
TI  - The functional range of motion of the finger joints.
AB  - The purpose of this study was to measure the functional range of motion of the
      finger joints needed to perform activities of daily living. Using the Sollerman
      hand grip function test, 20 activities were assessed in ten volunteers. The
      active and passive range of motion was measured with a computerized electric
      goniometer. The position of each finger joint was evaluated in the pre-grasp and
      grasp positions. The functional range of motion was defined as the range required
      to perform 90% of the activities, utilizing the pre-grasp and grasp measurements.
      The functional range of motion was 19 degrees -71 degrees , 23 degrees -87
      degrees , and 10 degrees -64 degrees  at the metacarpophalangeal, proximal
      interphalangeal, and distal interphalangeal joints, respectively. This represents
      48%, 59%, and 60% of the active motion of these joints, respectively. There was a
      significant difference in the functional range of motion between the joints of
      the fingers, with the ulnar digits having greater active and functional range.
      The functional range of motion is important for directing indications for surgery
      and rehabilitation, and assessing outcome of treatment. 

PMID- 24859990
TI  - Aberrant DNA hypermethylation of SDHC: a novel mechanism of tumor development in
      Carney triad.
AB  - Carney triad (CT) is a rare condition with synchronous or metachronous occurrence
      of gastrointestinal stromal tumors (GISTs), paragangliomas (PGLs), and pulmonary
      chondromas in a patient. In contrast to Carney-Stratakis syndrome (CSS) and
      familial PGL syndromes, no germline or somatic mutations in the succinate
      dehydrogenase (SDH) complex subunits A, B, C, or D have been found in most tumors
      and/or patients with CT. Nonetheless, the tumors arising among patients with CT,
      CSS, or familial PGL share a similar morphology with loss of the SDHB subunit on
      the protein level. For the current study, we employed massive parallel bisulfite
      sequencing to evaluate DNA methylation patterns in CpG islands in proximity to
      the gene loci of all four SDH subunits. For the first time, we report on a
      recurrent aberrant dense DNA methylation at the gene locus of SDHC in tumors of
      patients with CT, which was not present in tumors of patients with CSS or PGL, or
      in sporadic GISTs with KIT mutations. This DNA methylation pattern was correlated
      to a reduced mRNA expression of SDHC, and concurrent loss of the SDHC subunit on
      the protein level. Collectively, these data suggest epigenetic inactivation of
      the SDHC gene locus with functional impairment of the SDH complex as a plausible
      alternate mechanism of tumorigenesis in CT.

PMID- 24859991
TI  - Biologic and clinical significance of androgen receptor variants in castration
      resistant prostate cancer.
AB  - As prostate cancer (PCa) progresses to the lethal castration resistant and
      metastatic form, genetic and epigenetic adaptation, clonal selection, and
      evolution of the tumor microenvironment contribute to the emergence of unique
      biological characteristics under the selective pressure of external stresses.
      These stresses include the therapies applied in the clinic or laboratory and the
      exposures of cancers to hormonal, paracrine, or autocrine stimuli in the context
      of the tumor micro- and macro-environment. The androgen receptor (AR) is a key
      gene involved in PCa etiology and oncogenesis, including disease development,
      progression, response to initial hormonal therapies, and subsequent resistance to
      hormonal therapies. Alterations in the AR signaling pathway have been observed in
      certain selection contexts and contribute to the resistance to agents that target
      hormonal regulation of the AR, including standard androgen deprivation therapy,
      antiandrogens such as enzalutamide, and androgen synthesis inhibition with
      abiraterone acetate. One such resistance mechanism is the synthesis of
      constitutively active AR variants lacking the canonical ligand-binding domain.
      This review focuses on the etiology, characterization, biological properties, and
      emerging data contributing to the clinical characteristics of AR variants, and
      suggests approaches to full-length AR and AR variant biomarker validation,
      assessment, and systemic targeting in the clinic.

PMID- 24859995
TI  - Surgical Management of Severe Colitis in the Intensive Care Unit.
AB  - Severe colitis, an umbrella encompassing several entities, is one of the most
      common acute gastrointestinal disorders resulting in critical illness.
      Clostridium difficile infection is responsible for the majority of nosocomial
      diarrhea with fulminant C difficile colitis (CDC) carrying a high mortality.
      Optimal outcomes can be achieved by early identification and treatment of
      fulminant CDC, with appropriate surgical intervention when indicated. Ischemic
      colitis, on the other hand, is uncommon with a range of etiological factors
      including abdominal aortic surgery, inotropic drugs, rheumatoid diseases, or
      often no obvious triggering factor. Most cases resolve with nonsurgical
      management; however, prompt recognition of full-thickness necrosis and gangrene
      is crucial for good patient outcomes. Fulminant colitis is a severe disease
      secondary to progressive ulcerative colitis with systemic deterioration. Surgical
      intervention is indicated for hemorrhage, perforation, or peritonitis and failure
      of medical therapy to control the disease. Although, failure of medical
      management is the most common indication, it can be difficult to define
      objectively and requires a collaborative multidisciplinary approach. This article
      proposes some simple management algorithms for these clinical entities, with a
      focus on critically ill patients. 

PMID- 24859994
TI  - Characterization of the chloroquine resistance transporter homologue in
      Toxoplasma gondii.
AB  - Mutations in the Plasmodium falciparum chloroquine resistance transporter (PfCRT)
      protein confer resistance to the antimalarial drug chloroquine. PfCRT localizes
      to the parasite digestive vacuole, the site of chloroquine action, where it
      mediates resistance by transporting chloroquine out of the digestive vacuole.
      PfCRT belongs to a family of transporter proteins called the chloroquine
      resistance transporter family. CRT family proteins are found throughout the
      Apicomplexa, in some protists, and in plants. Despite the importance of PfCRT in
      drug resistance, little is known about the evolution or native function of CRT
      proteins. The apicomplexan parasite Toxoplasma gondii contains one CRT family
      protein. We demonstrate that T. gondii CRT (TgCRT) colocalizes with markers for
      the vacuolar (VAC) compartment in these parasites. The TgCRT-containing VAC is a
      highly dynamic organelle, changing its morphology and protein composition between
      intracellular and extracellular forms of the parasite. Regulated knockdown of
      TgCRT expression resulted in modest reduction in parasite fitness and swelling of
      the VAC, indicating that TgCRT contributes to parasite growth and VAC physiology.
      Together, our findings provide new information on the role of CRT family proteins
      in apicomplexan parasites. 

PMID- 24859996
TI  - A case of overlap syndrome successfully treated with tocilizumab: a hopeful
      treatment strategy for refractory dermatomyositis?

PMID- 24859997
TI  - Predictors of host specificity among behavior-manipulating parasites.
AB  - A trade-off between resource-specialization and the breadth of the ecological
      niche is one of the most fundamental biological characteristics. A true
      generalist (Jack-of-all-trades) displays a broad ecological niche with little
      resource specialization while the opposite is true for a resource-specialist that
      has a restricted ecological niche that it masters. Parasites that manipulate
      hosts' behavior are often thought to represent resource-specialists based on a
      few spectacular examples of manipulation of the host's behavior. However, the
      determinants of which, and how many, hosts a manipulating parasite can exploit
      (i.e., niche breadth) are basically unknown. Here, I present an analysis based on
      published records of the use of hosts by 67 species from 38 genera of helminths
      inducing parasite increased trophic transmission, a widespread strategy of
      parasites that has been reported from many taxa of parasites and hosts. Using
      individual and multivariate analyses, I examined the effect of the host's and
      parasite's taxonomy, location of the parasite in the host, type of behavioral
      change, and the effect of debilitation on host-specificity, measured as the mean
      taxonomic relatedness of hosts that a parasite can manipulate. Host-specificity
      varied substantially across taxa suggesting great variation in the level of
      resource-specialization among manipulating parasites. Location of the parasite,
      level of debilitation, and type of host were all significant predictors of host
      specificity. More specifically, hosts' behavioral modification that involves
      interaction with the central nervous system presumably restricts parasites to
      more closely related hosts than does manipulation of the host's behavior via
      debilitation of the host's physiology. The results of the analysis suggest that
      phylogenetic relatedness of hosts is a useful measure of host-specificity in
      comparative studies of the complexity of interactions taking place between
      manipulating parasites and their hosts. 

PMID- 24859998
TI  - KRAS, NRAS and BRAF mutations in Greek and Romanian patients with colorectal
      cancer: a cohort study.
AB  - OBJECTIVES: Treatment decision-making in colorectal cancer is often guided by
      tumour tissue molecular analysis. The aim of this study was the development and
      validation of a high-resolution melting (HRM) method for the detection of KRAS,
      NRAS and BRAF mutations in Greek and Romanian patients with colorectal cancer and
      determination of the frequency of these mutations in the respective populations.
      SETTING: Diagnostic molecular laboratory located in Athens, Greece. PARTICIPANTS:
      2425 patients with colorectal cancer participated in the study. PRIMARY AND
      SECONDARY OUTCOME MEASURES: 2071 patients with colorectal cancer (1699 of Greek
      and 372 of Romanian origin) were analysed for KRAS exon 2 mutations. In addition,
      354 tumours from consecutive patients (196 Greek and 161 Romanian) were subjected
      to full KRAS (exons 2, 3 and 4), NRAS (exons 2, 3 and 4) and BRAF (exon 15)
      analysis. KRAS, NRAS and BRAF mutation detection was performed by a newly
      designed HRM analysis protocol, followed by Sanger sequencing. RESULTS: KRAS exon
      2 mutations (codons 12/13) were detected in 702 of the 1699 Greek patients with
      colorectal carcinoma analysed (41.3%) and in 39.2% (146/372) of the Romanian
      patients. Among the 354 patients who were subjected to full KRAS, NRAS and BRAF
      analysis, 40.96% had KRAS exon 2 mutations (codons 12/13). Among the KRAS exon 2
      wild-type patients 15.31% harboured additional RAS mutations and 12.44% BRAF
      mutations. The newly designed HRM method used showed a higher sensitivity
      compared with the sequencing method. CONCLUSIONS: The HRM method developed was
      shown to be a reliable method for KRAS, NRAS and BRAF mutation detection.
      Furthermore, no difference in the mutation frequency of KRAS, NRAS and BRAF was
      observed between Greek and Romanian patients with colorectal cancer.

PMID- 24860000
TI  - Which features of primary care affect unscheduled secondary care use? A
      systematic review.
AB  - OBJECTIVES: To conduct a systematic review to identify studies that describe
      factors and interventions at primary care practice level that impact on levels of
      utilisation of unscheduled secondary care. SETTING: Observational studies at
      primary care practice level. PARTICIPANTS: Studies included people of any age of
      either sex living in Organisation for Economic Co-operation and Development
      (OECD) countries with any health condition. PRIMARY AND SECONDARY OUTCOME
      MEASURES: The primary outcome measure was unscheduled secondary care as measured
      by emergency department attendance and emergency hospital admissions. RESULTS: 48
      papers were identified describing potential influencing features on emergency
      department visits (n=24 studies) and emergency admissions (n=22 studies). Patient
      factors associated with both outcomes were increased age, reduced socioeconomic
      status, lower educational attainment, chronic disease and multimorbidity.
      Features of primary care affecting unscheduled secondary care were more complex.
      Being able to see the same healthcare professional reduced unscheduled secondary
      care. Generally, better access was associated with reduced unscheduled care in
      the USA. Proximity to healthcare provision influenced patterns of use. Evidence
      relating to quality of care was limited and mixed. CONCLUSIONS: The majority of
      research was from different healthcare systems and limited in the extent to which
      it can inform policy. However, there is evidence that continuity of care is
      associated with reduced emergency department attendance and emergency hospital
      admissions.

PMID- 24859999
TI  - Cross-sectional survey of attitudes and beliefs about back pain in New Zealand.
AB  - OBJECTIVES: To explore the prevalence of attitudes and beliefs about back pain in
      New Zealand and compare certain beliefs based on back pain history or health
      professional exposure. DESIGN: Population-based cross-sectional survey. SETTING:
      Postal survey. PARTICIPANTS: New Zealand residents and citizens aged 18 years and
      above. 1000 participants were randomly selected from the New Zealand Electoral
      Roll. Participants listed on the Electoral Roll with an overseas postal address
      were excluded. 602 valid responses were received. MEASURES: Attitudes and beliefs
      about back pain were measured with the Back Pain Attitudes Questionnaire (Back
      PAQ). The interaction between attitudes and beliefs and (1) back pain experience
      and (2) health professional exposure was investigated. RESULTS: The lifetime
      prevalence of back pain was reported as 87% (95% CI 84% to 90%), and the point
      prevalence as 27% (95% CI 24% to 31%). Negative views about the back and back
      pain were prevalent, in particular the need to protect the back to prevent
      injury. People with current back pain had more negative overall scores,
      particularly related to back pain prognosis. There was uncertainty about links
      between pain and injury and appropriate physical activity levels during an
      episode of back pain. Respondents had more positive views about activity if they
      had consulted a health professional about back pain. The beliefs of New
      Zealanders appeared to be broadly similar to those of other Western populations.
      CONCLUSIONS: A large proportion of respondents believed that they needed to
      protect their back to prevent injury; we theorise that this belief may result in
      reduced confidence to use the back and contribute to fear avoidance. Uncertainty
      regarding what is a safe level of activity during an episode of back pain may
      limit participation. People experiencing back pain may benefit from more targeted
      information about the positive prognosis. The provision of clear guidance about
      levels of activity may enable confident participation in an active recovery.

PMID- 24860001
TI  - Lactate clearance as a useful biomarker for the prediction of all-cause mortality
      in critically ill patients: a systematic review study protocol.
AB  - INTRODUCTION: Arterial lactate is a reflection of balance between lactate
      production and clearance. Accumulating lactate may be a marker of global hypoxia
      or hypoperfusion. Lactate clearance is the reduction of lactate concentrations
      with interventional strategies, and it has been associated with increased risk of
      death in critically ill patients. However, conflicting results exist, which
      mandates a systematic review to clarify the association between lactate clearance
      and clinical outcome. METHODS AND ANALYSIS: Critically ill adult patients will be
      included in our analysis. This population will include heterogeneous study
      participants, including patients with sepsis or severe sepsis, trauma, surgical
      intensive care unit (ICU) patients, and so on. We will search four databases
      including EBSCO, PubMed, Scopus and ISI Web of knowledge from inception to
      February 2014. There will be no language restrictions in the electronic search
      for studies. Newcastle Ottawa Scale for cohort study will be employed to assess
      the reporting quality of included original studies. We will report pooled
      relative risk of death for those with lactate clearance and those without. The
      diagnostic performance of lactate clearance in predicting mortality will be
      explored by using the hierarchical summary receiver operating characteristic
      model. ETHICS AND DISSEMINATION: The protocol for the systematic review has been
      registered in PROSPERO. The study will be disseminated electronically and in
      print. It will also be presented to conferences related to critical care
      medicine. TRIAL REGISTRATION NUMBER: CRD42013006511.

PMID- 24860002
TI  - Towards tailoring of self-management for patients with chronic heart failure or
      chronic obstructive pulmonary disease: a protocol for an individual patient data
      meta-analysis.
AB  - INTRODUCTION: Self-management interventions in patients with chronic conditions
      have received increasing attention over the past few years, yet the meta-analyses
      encountered considerable heterogeneity in results. This suggests that the
      effectiveness of self-management interventions must be assessed in the context of
      which components are responsible for eliciting the effect and in which subgroups
      of patients the intervention works best. The aim of the present study is to
      identify condition-transcending determinants of success of self-management
      interventions in two parallel individual patient data meta-analyses of self
      management trials in patients with congestive heart failure (CHF) and in patients
      with chronic obstructive pulmonary disease (COPD). METHODS AND ANALYSIS:
      Investigators of 53 randomised trials (32 in CHF and 21 in COPD) will be
      requested to share their de-identified individual patient data. Data will be
      analysed using random effects models, taking clustering within studies into
      account. Effect modification by age, sex, disease severity, symptom status,
      comorbid conditions and level of education will be assessed. Sensitivity analyses
      will be conducted to assess the robustness of the findings. ETHICS AND
      DISSEMINATION: The de-identified individual patient data are used only for the
      purpose for which they were originally collected and for which ethical approval
      has been obtained by the original investigators. Knowledge on the effective
      ingredients of self-management programmes and identification of subgroups of
      patients in which those interventions are most effective will guide the
      development of evidence-based personalised self-management interventions for
      patients with CHF and COPD as well as with other chronic diseases. TRIAL
      REGISTRATION NUMBER PROSPERO: CRD42013004698.

PMID- 24860003
TI  - The development and exploratory analysis of the Back Pain Attitudes Questionnaire
      (Back-PAQ).
AB  - OBJECTIVES: To develop an instrument to assess attitudes and underlying beliefs
      about back pain, and subsequently investigate its internal consistency and
      underlying structures. DESIGN: The instrument was developed by a
      multidisciplinary team of clinicians and researchers based on analysis of
      qualitative interviews with people experiencing acute and chronic back pain.
      Exploratory analysis was conducted using data from a population-based cross
      sectional survey. SETTING: Qualitative interviews with community-based
      participants and subsequent postal survey. PARTICIPANTS: Instrument development
      informed by interviews with 12 participants with acute back pain and 11
      participants with chronic back pain. Data for exploratory analysis collected from
      New Zealand residents and citizens aged 18 years and above. 1000 participants
      were randomly selected from the New Zealand Electoral Roll. 602 valid responses
      were received. MEASURES: The 34-item Back Pain Attitudes Questionnaire (Back-PAQ)
      was developed. Internal consistency was evaluated by the Cronbach alpha
      coefficient. Exploratory analysis investigated the structure of the data using
      Principal Component Analysis. RESULTS: The 34-item long form of the scale had
      acceptable internal consistency (alpha=0.70; 95% CI 0.66 to 0.73). Exploratory
      analysis identified five two-item principal components which accounted for 74% of
      the variance in the reduced data set: 'vulnerability of the back'; 'relationship
      between back pain and injury'; 'activity participation while experiencing back
      pain'; 'prognosis of back pain' and 'psychological influences on recovery'.
      Internal consistency was acceptable for the reduced 10-item scale (alpha=0.61;
      95% CI 0.56 to 0.66) and the identified components (alpha between 0.50 and 0.78).
      CONCLUSIONS: The 34-item long form of the scale may be appropriate for use in
      future cross-sectional studies. The 10-item short form may be appropriate for use
      as a screening tool, or an outcome assessment instrument. Further testing of the
      10-item Back-PAQ's construct validity, reliability, responsiveness to change and
      predictive ability needs to be conducted.

PMID- 24860004
TI  - Preterm nutritional intake and MRI phenotype at term age: a prospective
      observational study.
AB  - OBJECTIVE: To describe (1) the relationship between nutrition and the preterm-at
      term infant phenotype, (2) phenotypic differences between preterm-at-term infants
      and healthy term born infants and (3) relationships between somatic and brain MRI
      outcomes. DESIGN: Prospective observational study. SETTING: UK tertiary neonatal
      unit. PARTICIPANTS: Preterm infants (<32 weeks gestation) (n=22) and healthy term
      infants (n=39) MAIN OUTCOME MEASURES: Preterm nutrient intake; total and regional
      adipose tissue (AT) depot volumes; brain volume and proximal cerebral arterial
      vessel tortuosity (CAVT) in preterm infants and in term infants. RESULTS: Preterm
      nutrition was deficient in protein and high in carbohydrate and fat. Preterm
      nutrition was not related to AT volumes, brain volume or proximal CAVT score; a
      positive association was noted between human milk intake and proximal CAVT score
      (r=0.44, p=0.05). In comparison to term infants, preterm infants had increased
      total adiposity, comparable brain volumes and reduced proximal CAVT scores. There
      was a significant negative correlation between deep subcutaneous abdominal AT
      volume and brain volume in preterm infants (r=-0.58, p=0.01). CONCLUSIONS: Though
      there are significant phenotypic differences between preterm infants at term and
      term infants, preterm macronutrient intake does not appear to be a determinant.
      Our preliminary data suggest that (1) human milk may exert a beneficial effect on
      cerebral arterial vessel tortuosity and (2) there is a negative correlation
      between adiposity and brain volume in preterm infants at term. Further work is
      warranted to see if our findings can be replicated and to understand the causal
      mechanisms.

PMID- 24860005
TI  - Prognostic implications of global LV dysfunction: a systematic review and meta
      analysis of global longitudinal strain and ejection fraction.
AB  - BACKGROUND: Global longitudinal strain (GLS) is a robust, well validated and
      reproducible technique for the measurement of LV longitudinal deformation. We
      sought to assemble evidence that GLS is an accurate marker in predicting
      cardiovascular outcomes, compared to LVEF. METHODS: We undertook a systematic
      review of the evidence from observational studies which compared GLS against LVEF
      in predicting major adverse cardiac events. The primary outcome was all-cause
      mortality. The secondary outcome was a composite of cardiac death, malignant
      arrhythmia, hospitalisation due to heart failure, urgent valve surgery or heart
      transplantation, and acute coronary ischaemic event. A random effects model was
      used to combine HR and 95% CIs. A meta-regression was undertaken to assess the
      impact of potential covariates. RESULTS: Data were collated from 16 published
      articles (n=5721 adults) comprising 15 prospective and 1 retrospective
      observational studies. The underlying cardiac conditions were heart failure,
      acute myocardial infarction, valvular heart disease, and miscellaneous cardiac
      diseases. Mortality was independently associated with each SD change in the
      absolute value of baseline GLS (HR 0.50, 95% CI 0.36 to 0.69; p<0.002) and less
      strongly with LVEF (HR 0.81, 95% CI 0.72 to 0.92; p=0.572). The HR per SD change
      in GLS was associated with a reduction in mortality 1.62 (95% CI 1.13 to 2.33;
      p=0.009) times greater than the HR per SD change in LVEF. CONCLUSIONS: There is
      strong evidence of the prognostic value of GLS, which appears to have superior
      prognostic value to EF for predicting major adverse cardiac events.

PMID- 24860006
TI  - Does the heart have a mind of its own? Prevent adverse outcome from Takotsubo
      cardiomyopathy.

PMID- 24860008
TI  - Going batty for jumping DNA as a cause of species diversity.

PMID- 24860007
TI  - Prediction of stroke or TIA in patients without atrial fibrillation using CHADS2
      and CHA2DS2-VASc scores.
AB  - OBJECTIVES: To determine the accuracy of CHADS2 and CHA2DS2-VASc tools for
      predicting ischaemic stroke or transient ischaemic attack (TIA) and death in
      patients without a history of atrial fibrillation or flutter (AF). METHODS: The
      study included 20 970 patients without known AF enrolled in the Alberta
      Provincial Project for Outcomes Assessment in Coronary Heart disease (APPROACH)
      prospective registry who were discharged after an acute coronary syndrome (ACS)
      between 2005 and 2011. The outcome measures were incident ischaemic stroke, TIA
      or death from any cause. RESULTS: Over a median follow-up of 4.1 years, 453
      patients (2.2%) had a stroke (n=297) or TIA (n=156) and 1903 (9.0%) died. The
      incidence of stroke or TIA increased with increases in each risk score (p<0.001),
      with an absolute annual incidence >=1% with CHADS2 >=3 or CHA2DS2-VASc >=4. Both
      CHADS2 and CHA2DS2-VASc scores had acceptable discrimination performance (C
      statistic=0.68 and 0.71, respectively). The mortality rate was also greater in
      patients with higher CHADS2 and CHA2DS2-VASc scores (p<0.0001). CONCLUSIONS: In
      patients with ACS but no AF, the CHADS2 and CHA2DS2-VASc scores predict ischaemic
      stroke/TIA events with similar accuracy to that observed in historical
      populations with non-valvular AF, but with lower absolute event rates. Further
      study of the utility of the CHADS2 and CHA2DS2-VASc scores for the assessment of
      thromboembolic risk and selection of antithrombotic therapy in patients without
      AF is warranted.

PMID- 24860012
TI  - Study yields "Genghis Khan" of brown bears, new understanding of brown and polar
      bear evolution.

PMID- 24860013
TI  - Identification of the RNA recognition element of the RBPMS family of RNA-binding
      proteins and their transcriptome-wide mRNA targets.
AB  - Recent studies implicated the RNA-binding protein with multiple splicing (RBPMS)
      family of proteins in oocyte, retinal ganglion cell, heart, and gastrointestinal
      smooth muscle development. These RNA-binding proteins contain a single RNA
      recognition motif (RRM), and their targets and molecular function have not yet
      been identified. We defined transcriptome-wide RNA targets using photoactivatable
      ribonucleoside-enhanced crosslinking and immunoprecipitation (PAR-CLIP) in HEK293
      cells, revealing exonic mature and intronic pre-mRNA binding sites, in agreement
      with the nuclear and cytoplasmic localization of the proteins. Computational and
      biochemical approaches defined the RNA recognition element (RRE) as a tandem CAC
      trinucleotide motif separated by a variable spacer region. Similar to other mRNA
      binding proteins, RBPMS family of proteins relocalized to cytoplasmic stress
      granules under oxidative stress conditions suggestive of a support function for
      mRNA localization in large and/or multinucleated cells where it is preferentially
      expressed. 

PMID- 24860014
TI  - A neutral pH thermal hydrolysis method for quantification of structured RNAs.
AB  - Riboswitch aptamers adopt diverse and complex tertiary structural folds that
      contain both single-stranded and double-stranded regions. We observe that this
      high degree of secondary structure leads to an appreciable hypochromicity that is
      not accounted for in the standard method to calculate extinction coefficients
      using nearest-neighbor effects, which results in a systematic underestimation of
      RNA concentrations. Here we present a practical method for quantifying riboswitch
      RNAs using thermal hydrolysis to generate the corresponding pool of
      mononucleotides, for which precise extinction coefficients have been measured.
      Thermal hydrolysis can be performed at neutral pH without reaction quenching,
      avoids the use of nucleases or expensive fluorescent dyes, and does not require
      generation of calibration curves. The accuracy of this method for determining RNA
      concentrations has been validated using quantitative (31)P-NMR calibrated to an
      external standard. We expect that this simple procedure will be generally useful
      for the accurate quantification of any sequence-defined RNA sample, which is
      often a critical parameter for in vitro binding and kinetic assays. 

PMID- 24860015
TI  - Ribosome-omics of the human ribosome.
AB  - The torrent of RNA-seq data becoming available not only furnishes an overview of
      the entire transcriptome but also provides tools to focus on specific areas of
      interest. Our focus on the synthesis of ribosomes asked whether the abundance of
      mRNAs encoding ribosomal proteins (RPs) matched the equimolar need for the RPs in
      the assembly of ribosomes. We were at first surprised to find, in the mapping
      data of ENCODE and other sources, that there were nearly 100-fold differences in
      the level of the mRNAs encoding the different RPs. However, after correcting for
      the mapping ambiguities introduced by the presence of more than 2000 pseudogenes
      derived from RP mRNAs, we show that for 80%-90% of the RP genes, the molar ratio
      of mRNAs varies less than threefold, with little tissue specificity.
      Nevertheless, since the RPs are needed in equimolar amounts, there must be
      sluggish or regulated translation of the more abundant RP mRNAs and/or
      substantial turnover of unused RPs. In addition, seven of the RPs have subsidiary
      genes, three of which are pseudogenes that have been "rescued" by the
      introduction of promoters and/or upstream introns. Several of these are
      transcribed in a tissue-specific manner, e.g., RPL10L in testis and RPL3L in
      muscle, leading to potential variation in ribosome structure from one tissue to
      another. Of the 376 introns in the RP genes, a single one is alternatively
      spliced in a tissue-specific manner. 

PMID- 24860016
TI  - The RNA exosome affects iron response and sensitivity to oxidative stress.
AB  - RNA degradation plays important roles for maintaining temporal control and
      fidelity of gene expression, as well as processing of transcripts. In
      Saccharomyces cerevisiae the RNA exosome is a major 3'-to-5' exoribonuclease and
      also has an endonuclease domain of unknown function. Here we report a
      physiological role for the exosome in response to a stimulus. We show that
      inactivating the exoribonuclease active site of Rrp44 up-regulates the iron
      uptake regulon. This up-regulation is caused by increased levels of reactive
      oxygen species (ROS) in the mutant. Elevated ROS also causes hypersensitivity to
      H2O2, which can be reduced by the addition of iron to H2O2 stressed cells.
      Finally, we show that the previously characterized slow growth phenotype of rrp44
      exo(-) is largely ameliorated during fermentative growth. While the molecular
      functions of Rrp44 and the RNA exosome have been extensively characterized, our
      studies characterize how this molecular function affects the physiology of the
      organism. 

PMID- 24860018
TI  - Prenatal Stress Produces Persistence of Remote Memory and Disrupts Functional
      Connectivity in the Hippocampal-Prefrontal Cortex Axis.
AB  - Prenatal stress is a risk factor for the development of neuropsychiatric
      disorders, many of which are commonly characterized by an increased persistence
      of aversive remote memory. Here, we addressed the effect of prenatal stress on
      both memory consolidation and functional connectivity in the hippocampal
      prefrontal cortex axis, a dynamical interplay that is critical for mnemonic
      processing. Pregnant mice of the C57BL6 strain were subjected to restraint
      stressed during the last week of pregnancy, and male offspring were behaviorally
      tested at adulthood for recent and remote spatial memory performance in the
      Barnes Maze test under an aversive context. Prenatal stress did not affect the
      acquisition or recall of recent memory. In contrast, it produced the persistence
      of remote spatial memory. Memory persistence was not associated with alterations
      in major network rhythms, such as hippocampal sharp-wave ripples (SWRs) or
      neocortical spindles. Instead, it was associated with a large decrease in the
      basal discharge activity of identified principal neurons in the medial prefrontal
      cortex (mPFC) as measured in urethane anesthetized mice. Furthermore, functional
      connectivity was disrupted, as the temporal coupling between neuronal discharge
      in the mPFC and hippocampal SWRs was decreased by prenatal stress. These results
      could be relevant to understand the biological basis of the persistence of
      aversive remote memories in stress-related disorders. 

PMID- 24860017
TI  - Thalamocortical Connectivity Correlates with Phenotypic Variability in Dystonia.
AB  - Dystonia is a brain disorder characterized by abnormal involuntary movements
      without defining neuropathological changes. The disease is often inherited as an
      autosomal-dominant trait with incomplete penetrance. Individuals with dystonia,
      whether inherited or sporadic, exhibit striking phenotypic variability, with
      marked differences in the somatic distribution and severity of clinical
      manifestations. In the current study, we used magnetic resonance diffusion tensor
      imaging to identify microstructural changes associated with specific limb
      manifestations. Functional MRI was used to localize specific limb regions within
      the somatosensory cortex. Microstructural integrity was preserved when assessed
      in subrolandic white matter regions somatotopically related to the clinically
      involved limbs, but was reduced in regions linked to clinically uninvolved
      (asymptomatic) body areas. Clinical manifestations were greatest in subjects with
      relatively intact microstructure in somatotopically relevant white matter
      regions. Tractography revealed significant phenotype-related differences in the
      visualized thalamocortical tracts while corticostriatal and corticospinal
      pathways did not differ between groups. Cerebellothalamic microstructural
      abnormalities were also seen in the dystonia subjects, but these changes were
      associated with genotype, rather than with phenotypic variation. The findings
      suggest that the thalamocortical motor system is a major determinant of dystonia
      phenotype. This pathway may represent a novel therapeutic target for individuals
      with refractory limb dystonia. 

PMID- 24860021
TI  - Motion compensation for ultrasound thermal imaging using motion-mapped reference
      model: an in vivo mouse study.
AB  - Ultrasound (US)-based thermal imaging is very sensitive to tissue motion, which
      is a major obstacle to apply US temperature monitoring to noninvasive thermal
      therapies of in vivo subjects. In this study, we aim to develop a motion
      compensation method for stable US thermal imaging in in vivo subjects. Based on
      the assumption that the major tissue motion is approximately periodic caused by
      respiration, we propose a motion compensation method for change in backscattered
      energy (CBE) with multiple reference frames. Among the reference frames, the most
      similar reference to the current frame is selected to subtract the respiratory
      induced motions. Since exhaustive reference searching in all stored reference
      frames can impede real-time thermal imaging, we improve the reference searching
      by using a motion-mapped reference model. We tested our method in six tumor
      bearing mice with high intensity focused ultrasound (HIFU) sonication in the
      tumor volume until the temperature had increased by 7 degrees C. The proposed
      motion compensation was evaluated by root-mean-square-error (RMSE) analysis
      between the estimated temperature by CBE and the measured temperature by
      thermocouple. As a result, the mean +/-SD RMSE in the heating range was 1.1+/-0.1
      degrees C with the proposed method, while the corresponding result without motion
      compensation was 4.3+/-2.6 degrees C. In addition, with the idea of motion-mapped
      reference frame, total processing time to produce a frame of thermal image was
      reduced in comparison with the exhaustive reference searching, which enabled the
      motion-compensated thermal imaging in 15 frames per second with 150 reference
      frames under 50% HIFU duty ratio.

PMID- 24860020
TI  - Dysregulation of TrkB Receptors and BDNF Function by Amyloid-beta Peptide is
      Mediated by Calpain.
AB  - Brain-derived neurotrophic factor (BDNF) and its high-affinity full-length (FL)
      receptor, TrkB-FL, play a central role in the nervous system by providing trophic
      support to neurons and regulating synaptic plasticity and memory. TrkB and BDNF
      signaling are impaired in Alzheimer's disease (AD), a neurodegenerative disease
      involving accumulation of amyloid-beta (Abeta) peptide. We recently showed that
      Abeta leads to a decrease of TrkB-FL receptor and to an increase of truncated
      TrkB receptors by an unknown mechanism. In the present study, we found that (1)
      Abeta selectively increases mRNA levels for the truncated TrkB isoforms without
      affecting TrkB-FL mRNA levels, (2) Abeta induces a calpain-mediated cleavage on
      TrkB-FL receptors, downstream of Shc-binding site, originating a new truncated
      TrkB receptor (TrkB-T') and an intracellular fragment (TrkB-ICD), which is also
      detected in postmortem human brain samples, (3) Abeta impairs BDNF function in a
      calpain-dependent way, as assessed by the inability of BDNF to modulate
      neurotransmitter (GABA and glutamate) release from hippocampal nerve terminals,
      and long-term potentiation in hippocampal slices. It is concluded that Abeta
      induced calpain activation leads to TrkB cleavage and impairment of BDNF
      neuromodulatory actions. 

PMID- 24860019
TI  - Path Complexity in Virtual Water Maze Navigation: Differential Associations with
      Age, Sex, and Regional Brain Volume.
AB  - Studies of human navigation in virtual maze environments have consistently linked
      advanced age with greater distance traveled between the start and the goal and
      longer duration of the search. Observations of search path geometry suggest that
      routes taken by older adults may be unnecessarily complex and that excessive path
      complexity may be an indicator of cognitive difficulties experienced by older
      navigators. In a sample of healthy adults, we quantify search path complexity in
      a virtual Morris water maze with a novel method based on fractal dimensionality.
      In a two-level hierarchical linear model, we estimated improvement in navigation
      performance across trials by a decline in route length, shortening of search
      time, and reduction in fractal dimensionality of the path. While replicating
      commonly reported age and sex differences in time and distance indices, a
      reduction in fractal dimension of the path accounted for improvement across
      trials, independent of age or sex. The volumes of brain regions associated with
      the establishment of cognitive maps (parahippocampal gyrus and hippocampus) were
      related to path dimensionality, but not to the total distance and time. Thus,
      fractal dimensionality of a navigational path may present a useful complementary
      method of quantifying performance in navigation. 

PMID- 24860022
TI  - Brain tumor segmentation based on local independent projection-based
      classification.
AB  - Brain tumor segmentation is an important procedure for early tumor diagnosis and
      radiotherapy planning. Although numerous brain tumor segmentation methods have
      been presented, enhancing tumor segmentation methods is still challenging because
      brain tumor MRI images exhibit complex characteristics, such as high diversity in
      tumor appearance and ambiguous tumor boundaries. To address this problem, we
      propose a novel automatic tumor segmentation method for MRI images. This method
      treats tumor segmentation as a classification problem. Additionally, the local
      independent projection-based classification (LIPC) method is used to classify
      each voxel into different classes. A novel classification framework is derived by
      introducing the local independent projection into the classical classification
      model. Locality is important in the calculation of local independent projections
      for LIPC. Locality is also considered in determining whether local anchor
      embedding is more applicable in solving linear projection weights compared with
      other coding methods. Moreover, LIPC considers the data distribution of different
      classes by learning a softmax regression model, which can further improve
      classification performance. In this study, 80 brain tumor MRI images with ground
      truth data are used as training data and 40 images without ground truth data are
      used as testing data. The segmentation results of testing data are evaluated by
      an online evaluation tool. The average dice similarities of the proposed method
      for segmenting complete tumor, tumor core, and contrast-enhancing tumor on real
      patient data are 0.84, 0.685, and 0.585, respectively. These results are
      comparable to other state-of-the-art methods. 

PMID- 24860023
TI  - A damper driven robotic end-point manipulator for functional rehabilitation
      exercises after stroke.
AB  - Stroke survivors may benefit from robotic assistance for relearning of functional
      movements. Current assistive devices are either passive, limited to only two
      dimensions or very powerful. However, for reach training, weight compensation and
      a little assistance with limited power is sufficient. We designed and evaluated a
      novel three-dimensional robotic manipulator, which is able to support the arm
      weight and assist functional reaching movements. Key points of the design are a
      damper-based drive train, giving an inherently safe system and its compact and
      lightweight design. The system is force actuated with a bandwidth of up to 2.3
      Hz, which is sufficient for functional arm movements. Maximal assistive forces
      are 15 N for the up/down and forward/backward directions and 10 N for the
      left/right direction. Force tracking errors are smaller than 1.5 N for all axes
      and the total weight of the robot is 25 kg. Furthermore, the device has shown its
      benefit for increasing reaching distance in a single-case study with a stroke
      subject. The newly developed system has the technical ability to assist the arm
      during movement, which is a prerequisite for successful training of stroke
      survivors. Therapeutic effects of the applied assistance need to be further
      evaluated. However, with its inherent safety and ease of use, this newly
      developed system even has the potential for home-based therapeutic training after
      stroke. 

PMID- 24860024
TI  - A system and method for online high-resolution mapping of gastric slow-wave
      activity.
AB  - High-resolution (HR) mapping employs multielectrode arrays to achieve spatially
      detailed analyses of propagating bioelectrical events. A major current limitation
      is that spatial analyses must currently be performed "off-line" (after
      experiments), compromising timely recording feedback and restricting experimental
      interventions. These problems motivated development of a system and method for
      "online" HR mapping. HR gastric recordings were acquired and streamed to a novel
      software client. Algorithms were devised to filter data, identify slow-wave
      events, eliminate corrupt channels, and cluster activation events. A graphical
      user interface animated data and plotted electrograms and maps. Results were
      compared against off-line methods. The online system analyzed 256-channel serosal
      recordings with no unexpected system terminations with a mean delay 18 s.
      Activation time marking sensitivity was 0.92; positive predictive value was 0.93.
      Abnormal slow-wave patterns including conduction blocks, ectopic pacemaking, and
      colliding wave fronts were reliably identified. Compared to traditional analysis
      methods, online mapping had comparable results with equivalent coverage of 90% of
      electrodes, average RMS errors of less than 1 s, and CC of activation maps of
      0.99. Accurate slow-wave mapping was achieved in near real-time, enabling
      monitoring of recording quality and experimental interventions targeted to
      dysrhythmic onset. This work also advances the translation of HR mapping toward
      real-time clinical application.

PMID- 24860025
TI  - Power-assistive finger exoskeleton with a palmar opening at the fingerpad.
AB  - This paper presents a powered finger exoskeleton with an open fingerpad, named
      the Open Fingerpad eXoskeleton (OFX). The palmar opening at the fingerpad allows
      for direct contact between the user's fingerpad and objects in order to make use
      of the wearer's own tactile sensation for dexterous manipulation. Lateral side
      walls at the end of the OFX's index finger module are equipped with custom load
      cells for estimating the wearer's pinch grip force. A pneumatic cylinder
      generates assistance force, which is determined according to the estimated pinch
      grip force. The OFX transmits the assistance force directly to the objects
      without exerting pressure on the wearer's finger. The advantage of the OFX over
      an exoskeleton with a closed fingerpad was validated experimentally. During
      static and dynamic manipulation of a test object, the OFX exhibited a lower
      safety margin than the closed exoskeleton, indicating a higher ability to adjust
      the grip force within an appropriate range. Furthermore, the benefit of force
      assistance in reducing the muscular burden was observed in terms of muscle
      fatigue during a static pinch grip. The median frequency (MDF) of the surface
      electromyography (sEMG) signal from the first dorsal interosseous (FDI) muscle
      displayed a lower reduction rate for the assisted condition, indicating a lower
      accumulation rate of muscle fatigue. 

PMID- 24860026
TI  - Torsional dynamics of steerable needles: modeling and fluoroscopic guidance.
AB  - Needle insertions underlie a diversity of medical interventions. Steerable
      needles provide a means by which to enhance existing needle-based interventions
      and facilitate new ones. Tip-steerable needles follow a curved path and can be
      steered by twisting the needle base during insertion, but this twisting excites
      torsional dynamics that introduce a discrepancy between the base and tip twist
      angles. Here, we model the torsional dynamics of a flexible rod-such as a tip
      steerable needle-during subsurface insertion and develop a new controller based
      on the model. The torsional model incorporates time-varying mode shapes to
      capture the changing boundary conditions inherent during insertion. Numerical
      simulations and physical experiments using two distinct setups-stereo camera
      feedback in semitransparent artificial tissue and feedback control with real-time
      X-ray imaging in optically opaque artificial tissue-demonstrate the need to
      account for torsional dynamics in control of the needle tip. 

PMID- 24860027
TI  - Adolescents' psychological health complaints and the economic recession in late
      2007: a multilevel study in 31 countries.
AB  - BACKGROUND: The recent economic recession, which began in 2007, has had a
      detrimental effect on the health of the adult population, but no study yet has
      investigated the impact of this downturn on adolescent health. This article
      uniquely examines the effect of the crisis on adolescents' psychological health
      complaints in a cross-national comparison. METHODS: Data came from the World
      Health Organization collaborative 'Health Behaviour in School-aged Children'
      study in 2005-06 and 2009-10. We measured change in psychological health
      complaints from before to during the recession in the context of changing adult
      and adolescent unemployment rates. Furthermore, we used logistic multilevel
      regression to model the impact of absolute unemployment in 2010 and its change
      rate between 2005-06 and 2009-10 on adolescents' psychological health complaints
      in 2010. RESULTS: Descriptive results showed that although youth and adult
      unemployment has increased during the economic crisis, rates of psychological
      health complaints among adolescents were unaffected in some countries and even
      decreased in others. Multilevel regression models support this finding and reveal
      that only youth unemployment in 2010 increased the likelihood of psychological
      health complaints, whereas its change rate in light of the recession as well as
      adult unemployment did not relate to levels of psychological health complaints.
      CONCLUSION: In contrast to recent findings, our study indicates that the negative
      shift of the recent recession on the employment market in several countries has
      not affected adolescents' psychological health complaints. Adolescents' well
      being instead seems to be influenced by the current situation on the labour
      market that shapes their occupational outlook.

PMID- 24860029
TI  - Single image interpolation via adaptive nonlocal sparsity-based modeling.
AB  - Single image interpolation is a central and extensively studied problem in image
      processing. A common approach toward the treatment of this problem in recent
      years is to divide the given image into overlapping patches and process each of
      them based on a model for natural image patches. Adaptive sparse representation
      modeling is one such promising image prior, which has been shown to be powerful
      in filling-in missing pixels in an image. Another force that such algorithms may
      use is the self-similarity that exists within natural images. Processing groups
      of related patches together exploits their correspondence, leading often times to
      improved results. In this paper, we propose a novel image interpolation method,
      which combines these two forces-nonlocal self-similarities and sparse
      representation modeling. The proposed method is contrasted with competitive and
      related algorithms, and demonstrated to achieve state-of-the-art results.

PMID- 24860028
TI  - The isometric log-ratio transform for probabilistic multi-label anatomical shape
      representation.
AB  - Sources of uncertainty in the boundaries of structures in medical images have
      motivated the use of probabilistic labels in segmentation applications. An
      important component in many medical image segmentation tasks is the use of a
      shape model, often generated by applying statistical techniques to training data.
      Standard statistical techniques (e.g., principal component analysis) often assume
      data lies in an unconstrained vector space, but probabilistic labels are
      constrained to the unit simplex. If these statistical techniques are used
      directly on probabilistic labels, relative uncertainty information can be
      sacrificed. A standard method for facilitating analysis of probabilistic labels
      is to map them to a vector space using the LogOdds transform. However, the
      LogOdds transform is asymmetric in one of the labels, which skews results in some
      applications. The isometric log-ratio (ILR) transform is a symmetrized version of
      the LogOdds transform, and is so named as it is an isometry between the Aitchison
      geometry, the inherent geometry of the simplex, and standard Euclidean geometry.
      We explore how to interpret the Aitchison geometry when applied to probabilistic
      labels in medical image segmentation applications. We demonstrate the differences
      when applying the LogOdds transform or the ILR transform to probabilistic labels
      prior to statistical analysis. Specifically, we show that statistical analysis of
      ILR transformed data better captures the variability of anatomical shapes in
      cases where multiple different foreground regions share boundaries (as opposed to
      foreground-background boundaries). 

PMID- 24860030
TI  - BRINT: binary rotation invariant and noise tolerant texture classification.
AB  - In this paper, we propose a simple, efficient, yet robust multiresolution
      approach to texture classification-binary rotation invariant and noise tolerant
      (BRINT). The proposed approach is very fast to build, very compact while
      remaining robust to illumination variations, rotation changes, and noise. We
      develop a novel and simple strategy to compute a local binary descriptor based on
      the conventional local binary pattern (LBP) approach, preserving the advantageous
      characteristics of uniform LBP. Points are sampled in a circular neighborhood,
      but keeping the number of bins in a single-scale LBP histogram constant and
      small, such that arbitrarily large circular neighborhoods can be sampled and
      compactly encoded over a number of scales. There is no necessity to learn a
      texton dictionary, as in methods based on clustering, and no tuning of parameters
      is required to deal with different data sets. Extensive experimental results on
      representative texture databases show that the proposed BRINT not only
      demonstrates superior performance to a number of recent state-of-the-art LBP
      variants under normal conditions, but also performs significantly and
      consistently better in presence of noise due to its high distinctiveness and
      robustness. This noise robustness characteristic of the proposed BRINT is
      evaluated quantitatively with different artificially generated types and levels
      of noise (including Gaussian, salt and pepper, and speckle noise) in natural
      texture images.

PMID- 24860031
TI  - Accelerated learning-based interactive image segmentation using pairwise
      constraints.
AB  - Algorithms for fully automatic segmentation of images are often not sufficiently
      generic with suitable accuracy, and fully manual segmentation is not practical in
      many settings. There is a need for semiautomatic algorithms, which are capable of
      interacting with the user and taking into account the collected feedback.
      Typically, such methods have simply incorporated user feedback directly. Here, we
      employ active learning of optimal queries to guide user interaction. Our work in
      this paper is based on constrained spectral clustering that iteratively
      incorporates user feedback by propagating it through the calculated affinities.
      The original framework does not scale well to large data sets, and hence is not
      straightforward to apply to interactive image segmentation. In order to address
      this issue, we adopt advanced numerical methods for eigen-decomposition
      implemented over a subsampling scheme. Our key innovation, however, is an active
      learning strategy that chooses pairwise queries to present to the user in order
      to increase the rate of learning from the feedback. Performance evaluation is
      carried out on the Berkeley segmentation and Graz-02 image data sets, confirming
      that convergence to high accuracy levels is realizable in relatively few
      iterations.

PMID- 24860032
TI  - Robust (semi) nonnegative graph embedding.
AB  - Nonnegative matrix factorization (NMF) has received considerable attention in
      image processing, computer vision, and patter recognition. An important variant
      of NMF is nonnegative graph embedding (NGE), which encodes the statistical or
      geometric information of data in the process of matrix factorization. The NGE
      offers a general framework for unsupervised/supervised settings. However, NGE
      like algorithms often suffer from noisy data, unreliable graphs, and noisy
      labels, which are commonly encountered in real-world applications. To address
      these issues, in this paper, we first propose a robust nonnegative graph
      embedding (RNGE) framework, where the joint sparsity in both graph embedding and
      data reconstruction endues robustness to undesirable noises. Next, we present a
      robust seminonnegative graph embedding (RsNGE) framework, which only constrains
      the coefficient matrix to be nonnegative while places no constraint on the base
      matrix. This extends the applicable range of RNGE to data which are not
      nonnegative and endows more discriminative power of the learnt base matrix. The
      RNGE/RsNGE provides a general formulation such that all the algorithms unified
      within the graph embedding framework can be easily extended to obtain their
      robust nonnegative/seminonnegative solutions. Further, we develop elegant
      multiplicative updating solutions that can solve RNGE/RsNGE efficiently and offer
      a rigorous convergence analysis. We conduct extensive experiments on four real
      world data sets and compare the proposed RNGE/RsNGE to other representative NMF
      variants and data factorization methods. The experimental results demonstrate the
      robustness and effectiveness of the proposed approaches.

PMID- 24860034
TI  - Scalable similarity search with topology preserving hashing.
AB  - Hashing-based similarity search techniques is becoming increasingly popular in
      large data sets. To capture meaningful neighbors, the topology of a data set,
      which represents the neighborhood relationships between its subregions and the
      relative proximities between the neighbors of each subregion, e.g., the relative
      neighborhood ranking of each subregion, should be exploited. However, most
      existing hashing methods are developed to preserve neighborhood relationships
      while ignoring the relative neighborhood proximities. Moreover, most hashing
      methods lack in providing a good result ranking, since there are often lots of
      results sharing the same Hamming distance to a query. In this paper, we propose a
      novel hashing method to solve these two issues jointly. The proposed method is
      referred to as topology preserving hashing (TPH). TPH is distinct from prior
      works by also preserving the neighborhood ranking. Based on this framework, we
      present three different TPH methods, including linear unsupervised TPH,
      semisupervised TPH, and kernelized TPH. Particularly, our unsupervised TPH is
      capable of mining semantic relationship between unlabeled data without supervised
      information. Extensive experiments on four large data sets demonstrate the
      superior performances of the proposed methods over several state-of-the-art
      unsupervised and semisupervised hashing techniques.

PMID- 24860033
TI  - Group sparse multiview patch alignment framework with view consistency for image
      classification.
AB  - No single feature can satisfactorily characterize the semantic concepts of an
      image. Multiview learning aims to unify different kinds of features to produce a
      consensual and efficient representation. This paper redefines part optimization
      in the patch alignment framework (PAF) and develops a group sparse multiview
      patch alignment framework (GSM-PAF). The new part optimization considers not only
      the complementary properties of different views, but also view consistency. In
      particular, view consistency models the correlations between all possible
      combinations of any two kinds of view. In contrast to conventional dimensionality
      reduction algorithms that perform feature extraction and feature selection
      independently, GSM-PAF enjoys joint feature extraction and feature selection by
      exploiting l(2,1)-norm on the projection matrix to achieve row sparsity, which
      leads to the simultaneous selection of relevant features and learning
      transformation, and thus makes the algorithm more discriminative. Experiments on
      two real-world image data sets demonstrate the effectiveness of GSM-PAF for image
      classification.

PMID- 24860035
TI  - Design, development, and clinical evaluation of the electronic mobility cane for
      vision rehabilitation.
AB  - This paper proposes a new electronic mobility cane (EMC) for providing obstacle
      detection and way-finding assistance to the visually impaired people. The main
      feature of this cane is that it constructs the logical map of the surrounding
      environment to deduce the priority information. It provides a simplified
      representation of the surrounding environment without causing any information
      overload. It conveys this priority information to the subject by using intuitive
      vibration, audio or voice feedback. The other novel features of the EMC are
      staircase detection and nonformal distance scaling scheme. It also provides
      information about the floor status. It consists of a low power embedded system
      with ultrasonic sensors and safety indicators. The EMC was subjected to series of
      clinical evaluations in order to verify its design and to assess its ability to
      assist the subjects in their daily-life mobility. Clinical evaluations were
      performed with 16 totally blind and four low vision subjects. All subjects walked
      controlled and the real-world test environments with the EMC and the traditional
      white cane. The evaluation results and significant scores of subjective
      measurements have shown the usefulness of the EMC in vision rehabilitation
      services. 

PMID- 24860036
TI  - Enhanced dynamic EMG-force estimation through calibration and PCI modeling.
AB  - To accurately estimate muscle forces using electromyogram (EMG) signals, precise
      EMG amplitude estimation, and a modeling scheme capable of coping with the
      nonlinearities and dynamics of the EMG-force relationship are needed. In this
      work, angle-based EMG amplitude calibration and parallel cascade identification
      (PCI) modeling are combined for EMG-based force estimation in dynamic
      contractions, including concentric and eccentric contractions of the biceps
      brachii and triceps brachii muscles. Angle-based calibration has been shown to
      improve surface EMG (SEMG) based force estimation during isometric contractions
      through minimization of the effects of joint angle related factors, and PCI
      modeling captures both the nonlinear and dynamic properties of the process. SEMG
      data recorded during constant force, constant velocity, and varying force,
      varying velocity flexion and extension trials are calibrated. The calibration
      values are obtained at specific elbow joint angles and interpolated to cover a
      continuous range of joint angles. The calibrated data are used in PCI models to
      estimate the force induced at the wrist. The experimental results show the
      effectiveness of the calibration scheme, combined with PCI modeling. For the
      constant force, constant velocity trials, minimum %RMSE of 8.3% is achieved for
      concentric contractions, 10.3% for eccentric contractions and 33.3% for fully
      dynamic contractions. Force estimation accuracy is superior in concentric
      contractions in comparison to eccentric contractions , which may be indicative of
      more nonlinearity in the eccentric SEMG-force relationship. 

PMID- 24860037
TI  - A computerized recognition system for the home-based physiotherapy exercises
      using an RGBD camera.
AB  - Computerized recognition of the home based physiotherapy exercises has many
      benefits and it has attracted considerable interest among the computer vision
      community. However, most methods in the literature view this task as a special
      case of motion recognition. In contrast, we propose to employ the three main
      components of a physiotherapy exercise (the motion patterns, the stance
      knowledge, and the exercise object) as different recognition tasks and embed them
      separately into the recognition system. The low level information about each
      component is gathered using machine learning methods. Then, we use a generative
      Bayesian network to recognize the exercise types by combining the information
      from these sources at an abstract level, which takes the advantage of domain
      knowledge for a more robust system. Finally, a novel postprocessing step is
      employed to estimate the exercise repetitions counts. The performance evaluation
      of the system is conducted with a new dataset which contains RGB (red, green, and
      blue) and depth videos of home-based exercise sessions for commonly applied
      shoulder and knee exercises. The proposed system works without any body-part
      segmentation, bodypart tracking, joint detection, and temporal segmentation
      methods. In the end, favorable exercise recognition rates and encouraging results
      on the estimation of repetition counts are obtained. 

PMID- 24860038
TI  - 'SWeRF-a method for estimating the relevant fine particle fraction in bulk
      materials for classification and labelling purposes' by Pensis, Luetzenkirchen,
      and Friede.

PMID- 24860039
TI  - Consolidating exposure scenario information for mixtures--experiences and
      challenges.
AB  - INTRODUCTION: The requirements of the European Union Regulation on the
      Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH),
      including the preparation of exposure scenarios for the communication of safe
      use, are focused on single substances. Since the chemical products used at
      workplaces are typically mixtures, it is important to ensure that accurate
      information is available regarding their safe use. The focus of the present study
      was on the methods for consolidating (combining) the information presented in the
      exposure scenarios of the individual components of a mixture. METHODS: We tested
      the applicability and comparability of three methods for consolidating the
      exposure scenario information on six real products, focusing on occupational
      exposure. Two of the reviewed methods were based on the identification of the
      critical components that determine the health effects and risk management of the
      product, and one was based on the selection of the most stringent risk management
      measures presented in the exposure scenarios of the components. RESULTS: The
      differences in the critical components recognised by the two critical component
      based methods revealed limitations in both of the methods. The quality and
      comprehensiveness of the consolidated scenarios produced by the two methods were
      generally of the same level, depended directly on the content of the exposure
      scenarios of the critical components. Choosing the most stringent risk management
      measures improved the comprehensiveness of the scenarios. All of the examined
      methods run the risk of communicating over-precautionary measures if the
      concentration of the components determining the level of protection is not taken
      into consideration. CONCLUSIONS: Of the three methods considered, we recommend
      the selection of the most stringent operational conditions and risk management
      measures as a conservative default approach for consolidating exposure scenario
      information. If a critical component-based approach is used, checking the
      adequacy of the consolidated scenario for the other components of the mixture is
      recommended. With all of the methods, further modification of the consolidated
      scenario may be necessary to achieve the intended level of protection.

PMID- 24860040
TI  - Active electrode IC for EEG and electrical impedance tomography with continuous
      monitoring of contact impedance.
AB  - The IC presented integrates the front-end for EEG and Electrical Impedance
      Tomography (EIT) acquisition on the electrode, together with electrode-skin
      contact impedance monitoring and EIT current generation, so as to improve signal
      quality and integration of the two techniques for brain imaging applications. The
      electrode size is less than 2 cm(2) and only 4 wires connect the electrode to the
      back-end. The readout circuit is based on a Differential Difference Amplifier and
      performs single-ended amplification and frequency division multiplexing of the
      three signals that are sent to the back-end on a single wire which also provides
      power supply. Since the system's CMRR is a function of each electrode's gain
      accuracy, an analysis is performed on how this is influenced by mismatches in
      passive and active components. The circuit is fabricated in 0.35 MUm CMOS process
      and occupies 4 mm(2), the readout circuit consumes 360 MUW, the input referred
      noise for bipolar EEG signal acquisition is 0.56 MUVRMS between 0.5 and 100 Hz
      and almost halves if only EEG signal is acquired. 

PMID- 24860041
TI  - Wireless and wearable EEG system for evaluating driver vigilance.
AB  - Brain activity associated with attention sustained on the task of safe driving
      has received considerable attention recently in many neurophysiological studies.
      Those investigations have also accurately estimated shifts in drivers' levels of
      arousal, fatigue, and vigilance, as evidenced by variations in their task
      performance, by evaluating electroencephalographic (EEG) changes. However,
      monitoring the neurophysiological activities of automobile drivers poses a major
      measurement challenge when using a laboratory-oriented biosensor technology. This
      work presents a novel dry EEG sensor based mobile wireless EEG system (referred
      to herein as Mindo) to monitor in real time a driver's vigilance status in order
      to link the fluctuation of driving performance with changes in brain activities.
      The proposed Mindo system incorporates the use of a wireless and wearable EEG
      device to record EEG signals from hairy regions of the driver conveniently.
      Additionally, the proposed system can process EEG recordings and translate them
      into the vigilance level. The study compares the system performance between
      different regression models. Moreover, the proposed system is implemented using
      JAVA programming language as a mobile application for online analysis. A case
      study involving 15 study participants assigned a 90 min sustained-attention
      driving task in an immersive virtual driving environment demonstrates the
      reliability of the proposed system. Consistent with previous studies, power
      spectral analysis results confirm that the EEG activities correlate well with the
      variations in vigilance. Furthermore, the proposed system demonstrated the
      feasibility of predicting the driver's vigilance in real time. 

PMID- 24860042
TI  - A comparison of US- versus MR-based 3-D Prostate Shapes Using Radial Basis
      Function Interpolation and Statistical Shape Models.
AB  - This paper presents a comparison of three-dimensional (3-D) segmentations of the
      prostate, based on two-dimensional (2-D) manually segmented contours, obtained
      using ultrasound (US) and magnetic resonance (MR) imaging data collected from 40
      patients diagnosed with localized prostate cancer and scheduled to receive
      brachytherapy treatment. The approach we propose here for 3-D prostate
      segmentation first uses radial basis function interpolation to construct a 3-D
      point distribution model for each prostate. Next, a modified principal axis
      transformation is utilized for rigid registration of the US and MR images of the
      same prostate in preparation for the following shape comparison. Then,
      statistical shape models are used to capture the segmented 3-D prostate
      geometries for the subsequent cross-modality comparison. Our study includes not
      only cross-modality geometric comparisons in terms of prostate volumes and
      dimensions, but also an investigation of interchangeability of the two imaging
      modalities in terms of automatic contour segmentation at the pre-implant planning
      stage of prostate brachytherapy treatment. By developing a new scheme to compare
      the two imaging modalities in terms of the segmented 3-D shapes, we have taken a
      first step necessary for building coupled US-MR segmentation strategies for
      prostate brachytherapy pre-implant planning, which at present is predominantly
      informed by US images only. 

PMID- 24860043
TI  - Rule extraction from support vector machines using ensemble learning approach: an
      application for diagnosis of diabetes.
AB  - Diabetes mellitus is a chronic disease and a worldwide public health challenge.
      It has been shown that 50-80% proportion of T2DM is undiagnosed. In this paper,
      support vector machines are utilized to screen diabetes, and an ensemble learning
      module is added, which turns the "black box" of SVM decisions into comprehensible
      and transparent rules, and it is also useful for solving imbalance problem.
      Results on China Health and Nutrition Survey data show that the proposed ensemble
      learning method generates rule sets with weighted average precision 94.2% and
      weighted average recall 93.9% for all classes. Furthermore, the hybrid system can
      provide a tool for diagnosis of diabetes, and it supports a second opinion for
      lay users. 

PMID- 24860044
TI  - Hierarchical ensemble of background models for PTZ-based video surveillance.
AB  - In this paper, we study a novel hierarchical background model for intelligent
      video surveillance with the pan-tilt-zoom (PTZ) camera, and give rise to an
      integrated system consisting of three key components: background modeling,
      observed frame registration, and object tracking. First, we build the
      hierarchical background model by separating the full range of continuous focal
      lengths of a PTZ camera into several discrete levels and then partitioning the
      wide scene at each level into many partial fixed scenes. In this way, the wide
      scenes captured by a PTZ camera through rotation and zoom are represented by a
      hierarchical collection of partial fixed scenes. A new robust feature is
      presented for background modeling of each partial scene. Second, we locate the
      partial scenes corresponding to the observed frame in the hierarchical background
      model. Frame registration is then achieved by feature descriptor matching via
      fast approximate nearest neighbor search. Afterwards, foreground objects can be
      detected using background subtraction. Last, we configure the hierarchical
      background model into a framework to facilitate existing object tracking
      algorithms under the PTZ camera. Foreground extraction is used to assist tracking
      an object of interest. The tracking outputs are fed back to the PTZ controller
      for adjusting the camera properly so as to maintain the tracked object in the
      image plane. We apply our system on several challenging scenarios and achieve
      promising results. 

PMID- 24860045
TI  - Hybrid adaptive classifier ensemble.
AB  - Traditional random subspace-based classifier ensemble approaches (RSCE) have
      several limitations, such as viewing the same importance for the base classifiers
      trained in different subspaces, not considering how to find the optimal random
      subspace set. In this paper, we design a general hybrid adaptive ensemble
      learning framework (HAEL), and apply it to address the limitations of RSCE. As
      compared with RSCE, HAEL consists of two adaptive processes, i.e., base
      classifier competition and classifier ensemble interaction, so as to adjust the
      weights of the base classifiers in each ensemble and to explore the optimal
      random subspace set simultaneously. The experiments on the real-world datasets
      from the KEEL dataset repository for the classification task and the cancer gene
      expression profiles show that: 1) HAEL works well on both the real-world KEEL
      datasets and the cancer gene expression profiles and 2) it outperforms most of
      the state-of-the-art classifier ensemble approaches on 28 out of 36 KEEL datasets
      and 6 out of 6 cancer datasets. 

PMID- 24860046
TI  - Structural generative descriptions for time series classification.
AB  - In this paper, we formulate a novel time series representation framework that
      captures the inherent data dependency of time series and that can be easily
      incorporated into existing statistical classification algorithms. The impact of
      the proposed data representation stage in the solution to the generic underlying
      problem of time series classification is investigated. The proposed framework,
      which we call structural generative descriptions moves the structural time series
      representation to the probability domain, and hence is able to combine
      statistical and structural pattern recognition paradigms in a novel fashion. Two
      algorithm instantiations based on the proposed framework are developed. The
      algorithms are tested and compared using different publicly available real-world
      benchmark data. Results reported in this paper show the potential of the proposed
      representation framework, which in the experiments investigated, performs better
      or comparable to state-of-the-art time series description techniques. 

PMID- 24860047
TI  - A competitive swarm optimizer for large scale optimization.
AB  - In this paper, a novel competitive swarm optimizer (CSO) for large scale
      optimization is proposed. The algorithm is fundamentally inspired by the particle
      swarm optimization but is conceptually very different. In the proposed CSO,
      neither the personal best position of each particle nor the global best position
      (or neighborhood best positions) is involved in updating the particles. Instead,
      a pairwise competition mechanism is introduced, where the particle that loses the
      competition will update its position by learning from the winner. To understand
      the search behavior of the proposed CSO, a theoretical proof of convergence is
      provided, together with empirical analysis of its exploration and exploitation
      abilities showing that the proposed CSO achieves a good balance between
      exploration and exploitation. Despite its algorithmic simplicity, our empirical
      results demonstrate that the proposed CSO exhibits a better overall performance
      than five state-of-the-art metaheuristic algorithms on a set of widely used large
      scale optimization problems and is able to effectively solve problems of
      dimensionality up to 5000. 

PMID- 24860049
TI  - [Thrombin generation assays and their clinical application].
AB  - Thrombin is a key enzyme of the coagulation system, having both pro- and
      anticoagulant functions. Thus, the generation of thrombin is one of the most
      important steps in coagulation. Global haemostasis assay, the so-called thrombin
      generation test is appropriate for its assessment. Since thrombin generation is
      sensible for both pro- and anticoagulant processes it can be applied for the
      general characterisation of the risk of thrombosis and bleeding, too. Clinical
      studies confirmed augmented thrombin generation in patients with high risk of
      venous or arterial thrombosis. Anticoagulant therapy (also novel oral
      anticoagulant treatment) can be monitored by thrombin generation. In case of
      haemophilia thrombin generation assays reflect bleeding severity. It is
      applicable for monitoring of both conventional haemophilia treatment and
      inhibitor-bypassing therapy, which is needed when inhibitors develop in patients.
      Standardization of thrombin generation methods and determination of cut off
      values are required before its application in clinical practice.

PMID- 24860048
TI  - Socioeconomic inequalities in access to specialized psychotropic prescribing
      among older Swedes: a register-based study.
AB  - BACKGROUND: Mental disorders among older adults are mainly treated with
      psychotropic drugs. Few of these drugs are, however, prescribed by specialized
      geriatricians or psychiatrists, but rather from general practitioners (GPs).
      Socioeconomic inequalities in access to specialist prescribing have been found in
      younger age groups. Hence, we aimed to investigate whether there are
      socioeconomic differences in access to geriatrician and psychiatrist prescribing
      of psychotropic drugs among older adults. METHODS: By record-linkage of The
      Swedish Prescribed Drug Register and The Swedish Education Register, we obtained
      information for persons aged 75-89 years who had filled a prescription for
      psychotropic drugs (antipsychotics, anxiolytics, hypnotic/sedatives or
      antidepressants) with information on prescriber specialty from July to October
      2005 (n = 221 579). Multinomial regression analysis was used to investigate
      whether education was associated with geriatrician and psychiatrist prescribing
      of psychotropic drugs. RESULTS: The vast majority of the psychotropic drugs were
      prescribed by 'GPs and other specialists' (~95% GPs). Older adults with higher
      educational level were more likely to be prescribed psychotropic drugs from
      psychiatrists and geriatricians. However, after adjustment for place of
      residence, the association between patient's education and prescription by a
      geriatrician disappeared, whereas the association with seeing a psychiatrist was
      only attenuated. CONCLUSION: Access to specialized prescribing of psychotropics
      is unequally distributed between socioeconomic groups of older adults in Sweden.
      This finding was partially confounded by place of residence for geriatrician but
      not for psychiatrist prescribing. Further research should examine if inequalities
      in specialized psychotropic prescribing translate into worse outcomes for
      socioeconomically deprived and non-metropolitan-living older individuals.

PMID- 24860050
TI  - [Dissolving anxiety as an essential ingredient for any therapy].
AB  - Anxiety frequently develops in human life and it is usually useful for the
      organism. Anxiety helps accomodation to the social environment, however, it may
      be harmful when it is intensive and long-lasting. It can also cause psychosomatic
      diseases. Anxiety may present itself as mild or moderate stress, psychosomatic
      diseases or psychiatric disorders. In the general practice, about one third of
      the patients suffer from anxiety, but it is not easy to identify these patients
      because of the frequent somatic complaints which may cover anxiety symptoms. The
      prevalence of anxiety disorders is between 12.6% and 17.2% per year and, in a
      considerable proportion of patients, both anxiety and depression are present.
      Therapy of anxiety is complex including psychopharmacotherapy (antidepressants,
      anxiolytics, hypnotics), psychotherapy and life style changes.

PMID- 24860051
TI  - [Heart rate variability is significantly reduced in non-diabetic patients with
      hypertension].
AB  - INTRODUCTIONS: Heart rate variability is reduced among patients with hypertension
      and/or with diabetes mellitus. Hypertension and diabetes show frequent co
      morbidity, but it is still not entirely clear whether heart rate variability is
      reduced in non-diabetic patients with hypertension. AIM: The aim of the authors
      was to evaluate the heart rate variability in hypertensive patients with and
      without diabetes and in control subjects. METHOD: 130 patients with hypertension,
      48 patients with hypertension and type 2 diabetes mellitus, and 87 control
      subjects were involved in the study. Minimum, mean and maximum heart rate, and
      parameters of heart rate variability were measured. RESULTS: The mean of minimum
      heart rate did not differ significantly between the three groups. However, all
      other parameters were significantly reduced in patients with hypertension with
      and without diabetes as compared to the control group. No significant differences
      were observed between hypertensive patients with and without diabetes mellitus.
      CONCLUSIONS: Heart rate variability is significantly reduced in non-diabetic
      patients with hypertension. It seems that type 2 diabetes results in no further
      significant reduction of heart rate variability in patients with hypertension.

PMID- 24860052
TI  - [Urgent cesarean section in a pregnant woman with carbon monoxide poisoning].
AB  - Recognition of carbon monoxide is difficult due to its plain physical-chemical
      properties. Carbon and gas operating heating systems may cause severe poisoning.
      Carbon-monoxide intoxication may generate severe hypoxic damage and it may cause
      death. The authors present the case of severe carbon monoxide poisoning affecting
      one young child and five adults, including a pregnant woman. Because the
      availability of hyperbaric oxygen therapy is limited in Hungary, urgent cesarean
      section was performed to avoid intrauterine hypoxic damage. The authors note that
      there are no standardized non-invasive methods for measuring fetal carbon
      monoxide level and that the level of carbon monoxide accumulation is higher and
      the clearance is longer in the fetus than in the mother. The pathophysiology of
      carbon monoxide intoxication and therapeutic options in pregnancy are discussed.

PMID- 24860053
TI  - [The Orvosi Hetilap (Hungarian Medical Journal) in the network of medical
      journals].
AB  - The role of networks is swiftly increasing in the production and communication of
      scientific knowledge. Network aspects have, therefore, an ever growing importance
      in the analysis of the scientific enterprise, as well. The present paper
      demonstrates some techniques of studying the network of scientific journals on
      the subject of seeking the position of Orvosi Hetilap (Hungarian Medical Journal)
      in the international journal network.

PMID- 24860054
TI  - [Long-forgotten machines and devices used in the diagnostics and therapy of
      cardiovascular diseases].

PMID- 24860056
TI  - [Die RN4CAST-studie - lessons (to be) learned].

PMID- 24860057
TI  - [Trapped in the body - lived experience and coping of individuals having
      Parkinson and their relatives with changed movement pattern caused by the
      disease].
AB  - People with Parkinson's disease suffer from various symptoms. Changed movement
      patterns frequently represent the prevailing symptom experience and influence the
      everyday life of the affected persons and their relatives. This qualitative study
      explores how persons with Parkinson's disease and their relatives experience the
      changed movement patterns and how they manage the consequential problems in their
      daily life. Eight persons with Parkinson's disease and six partners were
      interviewed. The interviews were analysed by means of content analysis according
      to Mayring. The qualitative analysis resulted in two main categories: "effects on
      the changed movement patterns on everyday life" and "coping skills for dealing
      with changed movement patterns". The experience of the affected person can be
      characterised by "being trapped in the body" as well as by a constantly slowing
      down daily life. The coping strategies are diverse, but all respondents seek to
      maintain mobility. Partners naturally support the affected persons and take over
      many tasks. This is associated with elevated distress and the feeling of having
      to be permanently present. Various coping strategies have to be promoted and
      included in daily care for people with Parkinson's disease. Consideration of the
      individual experience of the changed movement patterns is very important in the
      development of strategies and also the support of the affected persons and
      relatives that they can keep up with their movements. 

PMID- 24860058
TI  - [Caregivers' needs concerning mobility support of a family member with terminal
      cancer - a narrative review].
AB  - BACKGROUND: Care for cancer patients is often provided by family caregivers. The
      terminal care period is usually associated with restricted mobility. AIM: The aim
      of this literature review is to analyse the needs of caregivers concerning
      mobility support and encouragement in everyday care of a cancer patient at the
      end of life. METHODS: Relevant articles were identified via electronic database
      searches in Cochrane, PubMed, PsychINFO, ERIC, and CINAHL. Studies examining
      needs concerning mobility support and encouragement for terminal cancer care
      provided by family caregivers at home, published in English or German, have been
      included. The methodological quality of the included studies was assessed by two
      authors. RESULTS: A total of eleven studies with various designs have been
      included. The results show a need for information, guidance and support regarding
      mobility in two areas: i) activities of daily living including personal hygiene
      and ii) usage of equipment including transport. CONCLUSION: The literature review
      indicates that practical needs of family caregivers concerning mobility support
      and encouragement have been assessed unsystematically and not yet adequately
      studied. This should be done in future studies, in order to implement well
      defined interventions for teaching nursing skills subsequently.

PMID- 24860059
TI  - [German translation and adaptation of the uncertainty stress scale high risk
      pregnancy version III (USS-HRPV) for hospitalised women with high-risk
      pregnancy].
AB  - BACKGROUND: A number of medical and societal factors currently contribute to an
      increasing number of women who are hospitalised because they are experiencing
      high-risk pregnancies. The unpredictability of the further course of pregnancy
      may lead to a feeling of uncertainty, as well as to stress, depending on coping
      strategies. AIMS: The aims of this study were thus to translate and adapt the USS
      HRPV so that uncertainty and stress could be systematically measured on affected
      women in German speaking areas. METHOD: Translation of the scale was undertaken
      by first translating into German and then back into English. The two-phase
      adaptation, carried out with affected women (n = 24) and midwives (n = 10),
      comprised cognitive interviews and testing of content validity using the Content
      Validity Index (CVI). Following each data collection phase the instrument was
      modified with the help of midwifery experts (n = 3). RESULTS: For each item the
      calculated CVI (I-CVI) in the first phase ranged between 0,10 and 1,0 for the
      sample of relevant women and midwives while the CVI of the total instrument (S
      CVI/Ave) was 0,62 and 0,70 respectively. In the second phase the I-CVI values of
      the hospitalised women ranged between 0,17 and 1,0 while the S-CVI/Ave value was
      0,73. With regard to all of the data, 44 of the original 86 items were removed
      and 28 altered on language grounds. CONCLUSIONS: As a result of the methodical
      approach utilised, a firm basis for further validation of the instrument for
      German speaking areas has been provided.

PMID- 24860061
TI  - [Life stage related search efforts in nursing career identity developments: from
      educational decision to career--a qualitative study in a panel design].

PMID- 24860060
TI  - [Conflict of interest with industry--a survey of nurses in the field of wound
      care in Germany, Australia and Switzerland].
AB  - BACKGROUND: Nurses in the field of wound care are increasingly being courted by
      the wound industry. OBJECTIVES: A survey regarding nurses' perceptions and
      participation in pharmaceutical marketing was conducted. METHODS: Based on
      existing instruments, a standardized questionnaire (39 items, 5-point Likert
      scale) was developed. It was sent electronically and by mail to all nursing
      members of the Austrian Society for Vascular Care (OGvP), the German Wound
      Healing Society (DGfW e. V.) and the Swiss Association for Wound Care (SAfW).
      RESULTS: 178 nurses participated in the survey (75 % women; aged 27 - 70 years
      [median 45], 0 - 40 years [median 9] practice in the area of the wound care).
      Only about one fourth of the respondents (23,0 %) did not participate in
      pharmaceutical marketing last year. Generally small gifts were more frequently
      received than expensive gifts. Most of the nurses valued inexpensive gifts,
      educational gifts and gifts with patient benefit as appropriate. The majority of
      respondents consider themselves as less influenceable in decision making,
      compared to physicians. CONCLUSIONS: The behavior and attitude of nurses are
      ambivalent. The occurrence of conflict of interest is partly justified by
      perceived patient benefit. Lack of knowledge about the topic and social
      desirability could be the cause of an uncritical attitude. For a more critical
      approach education and ethical standards are necessary.

PMID- 24860062
TI  - [Decubitus ulcer risk scale and new models of the decubitus ulcer development].

PMID- 24860069
TI  - Astringency: a more stringent definition.
AB  - Despite being an everyday sensory experience, the nature of astringency
      perception is not clear. In this issue of Chemical Senses, Schobel et al.
      demonstrate that astringency is a trigeminal sensation in human, and astringents
      trigger a G protein-coupled pathway in trigeminal ganglion cells in the mouse. 

PMID- 24860070
TI  - Daily collection of self-reporting sleep disturbance data via a smartphone app in
      breast cancer patients receiving chemotherapy: a feasibility study.
AB  - BACKGROUND: Improvements in mobile telecommunication technologies have enabled
      clinicians to collect patient-reported outcome (PRO) data more frequently, but
      there is as yet limited evidence regarding the frequency with which PRO data can
      be collected via smartphone applications (apps) in breast cancer patients
      receiving chemotherapy. OBJECTIVE: The primary objective of this study was to
      determine the feasibility of an app for sleep disturbance-related data collection
      from breast cancer patients receiving chemotherapy. A secondary objective was to
      identify the variables associated with better compliance in order to identify the
      optimal subgroups to include in future studies of smartphone-based interventions.
      METHODS: Between March 2013 and July 2013, patients who planned to receive
      neoadjuvant chemotherapy for breast cancer at Asan Medical Center who had access
      to a smartphone app were enrolled just before the start of their chemotherapy and
      asked to self-report their sleep patterns, anxiety severity, and mood status via
      a smartphone app on a daily basis during the 90-day study period. Push
      notifications were sent to participants daily at 9 am and 7 pm. Data regarding
      the patients' demographics, interval from enrollment to first self-report,
      baseline Beck's Depression Inventory (BDI) score, and health-related quality of
      life score (as assessed using the EuroQol Five Dimensional [EQ5D-3L]
      questionnaire) were collected to ascertain the factors associated with compliance
      with the self-reporting process. RESULTS: A total of 30 participants (mean age 45
      years, SD 6; range 35-65 years) were analyzed in this study. In total, 2700 daily
      push notifications were sent to these 30 participants over the 90-day study
      period via their smartphones, resulting in the collection of 1215 self-reporting
      sleep-disturbance data items (overall compliance rate=45.0%, 1215/2700). The
      median value of individual patient-level reporting rates was 41.1% (range 6.7
      95.6%). The longitudinal day-level compliance curve fell to 50.0% at day 34 and
      reached a nadir of 13.3% at day 90. The cumulative longitudinal compliance curve
      exhibited a steady decrease by about 50% at day 70 and continued to fall to 45%
      on day 90. Women without any form of employment exhibited the higher compliance
      rate. There was no association between any of the other patient characteristics
      (ie, demographics, and BDI and EQ5D-3L scores) and compliance. The mean
      individual patient-level reporting rate was higher for the subgroup with a 1-day
      lag time, defined as starting to self-report on the day immediately after
      enrollment, than for those with a lag of 2 or more days (51.6%, SD 24.0 and
      29.6%, SD 25.3, respectively; P=.03). CONCLUSIONS: The 90-day longitudinal
      collection of daily self-reporting sleep-disturbance data via a smartphone app
      was found to be feasible. Further research should focus on how to sustain
      compliance with this self-reporting for a longer time and select subpopulations
      with higher rates of compliance for mobile health care.

PMID- 24860071
TI  - The Origin and Impact of Ideals in eHealth Research: Experiences From the U-CARE
      Research Environment.
AB  - BACKGROUND: The prevalence of information technology (IT) in society is a
      foundation for new modes of interaction between patients and health specialists.
      IT plays an important role in the renewal of care. Several countries have
      incorporated eHealth plans into their national health strategies. Part of the
      eHealth evolution concerns Internet psychological treatment and psychosocial
      care. These interventions are complex to design and evaluate due to legal,
      ethical, organizational, technical, and methodological challenges. OBJECTIVE: The
      objective of our study was to seek to make explicit contributions to the
      understanding of ideals in eHealth research, and illuminate their implications
      for establishing an effective research environment. Our analysis draws from three
      years of experience in establishing an eHealth research environment, and the
      literature. METHODS: We worked inductively to characterize challenging research
      ideals, and their origins, in our environment. Thereafter, we made a selective
      search of the literature to scrutinize and illuminate each ideal and it's
      implications. RESULTS: In this work, we propose a structured approach to address
      ideals in eHealth research. The scrutinized ideals are accountability,
      innovation, rigor, relevance, and sustainability. The approach supports
      researchers to systematically understand the ideals, their origin, and to manage
      their implications within an eHealth research environment. CONCLUSIONS: The
      complexity of eHealth research causes a need for sustainable, multi-disciplinary
      research environments. There is a need for a structured approach to organize
      eHealth research. The proposed approach helps to systematically scrutinize
      ideals, thus promoting high quality research.

PMID- 24860072
TI  - First do no harm: is it any longer safe to write case reports?
AB  - This article explores the risks to authors and their clients of creating
      psychological literature based on case studies. The author considers how the
      events that occurred in Nicole Taus's case might have affected those clients with
      whom she wrote case studies. Finally, the author analyzes the potential losses to
      the field should other participants in case studies be at risk of the kind of
      intrusive invasion of privacy experienced by Taus and calls for the development
      of ethical principles for psychological science. 

PMID- 24860073
TI  - Introduction to special issue on violence against people with disability.

PMID- 24860074
TI  - Labeling of sexual assault and its relationship with sexual functioning: the
      mediating role of coping.
AB  - Little research has examined the relationship between women's labeling of their
      sexual assault experiences and sexual functioning, as well as identification of
      variables that may mediate the labeling-trauma outcome relationship. The purpose
      of this study was to fill this gap in the literature, by examining the potential
      mediating role of coping strategies in response to sexual assault in the
      relationship between labeling and sexual functioning. The sample included 135
      college women with a history of adolescent/early adulthood sexual assault.
      Labeling was not bivariately related to sexual functioning outcomes; however,
      anxious coping mediated the relationships between labeling and both sexual
      lubrication and sexual satisfaction. This suggests that correlational analyses
      between labeling and trauma outcomes may not capture the complexity of this
      relationship, as it may be more indirect. Furthermore, results suggest that
      labeling is part of the coping process in response to sexual assault; some women
      who consider their experience to be sexual assault may engage in anxious coping
      efforts, contributing to difficulties with sexual lubrication and sexual
      dissatisfaction. Victims actively working to integrate their sexual assault
      experience with prior beliefs and self-concept may benefit from treatment focused
      on decreasing anxious coping, especially as it relates to sexual functioning. 

PMID- 24860075
TI  - Evaluating the Chinese Revised Controlling Behaviors Scale.
AB  - The present study evaluated the utility of the Chinese version of the Revised
      Controlling Behaviors Scale (C-CBS-R) as a measure of controlling behaviors in
      violent Chinese intimate relationships. Using a mixed-methods approach, in-depth,
      individual interviews were conducted with 200 Chinese women survivors to elicit
      qualitative data about their personal experiences of control in intimate
      relationships. The use of controlling behaviors was also assessed using the C-CBS
      R. Interview accounts suggested that the experiences of 91 of the women were
      consistent with the description of coercive control according to Dutton and
      Goodman's conceptualization of coercion. Using the split-half validation
      procedure, a receiver operating characteristics (ROC) curve analysis was
      conducted with the first half of the sample. The area under the curve (AUC) for
      using the C-CBS-R to identify high control was .99, and the cutoff score of 1.145
      maximized both sensitivity and specificity. Applying the cutoff score to the
      second half gave a sensitivity of 96% and a specificity of 95%. Overall, the C
      CBS-R has demonstrated utility as a measure of controlling behaviors with a
      cutoff score for distinguishing high from low levels of control in violent
      Chinese intimate relationships. 

PMID- 24860076
TI  - Intimate partner violence in the relationships of men with disabilities in the
      United States: relative prevalence and health correlates.
AB  - Despite the growing literature on intimate partner violence (IPV) victimization
      against people with disabilities, few studies have examined IPV against men with
      disabilities. This study uses population-based data to examine the prevalence of
      past-year and lifetime IPV against men with disabilities in the United States in
      comparison with men without disabilities and women with and without disabilities,
      compare the demographic characteristics of men with disabilities who reported IPV
      to those of other men, and examine associations of IPV and disability status with
      mental and physical health and other health risks among men. Results indicate
      that, adjusting for demographic characteristics, men with disabilities were more
      likely to report lifetime IPV than men without disabilities and, among those
      reporting any lifetime IPV, men with disabilities were more likely to report past
      year IPV than both nondisabled men and women. With few exceptions, comparisons of
      health indicators revealed that men with disabilities reporting lifetime IPV were
      more likely than other men to report poor health status and to report engaging in
      health risk behaviors. Directions for future research and programmatic and policy
      implications of these results are discussed. 

PMID- 24860077
TI  - Prevalence and experiences of intimate partner violence against women with
      disabilities in Bangladesh: results of an explanatory sequential mixed-method
      study.
AB  - This study was aimed to estimate the prevalence of intimate partner violence
      (IPV) in a sample of 226 women with disabilities living in four different
      districts of Bangladesh. It also explored the physical and psychological
      suffering of women experiencing violence and their various coping strategies. A
      cross-sectional survey was carried out with 226 women with disabilities to
      measure the prevalence of IPV, and 16 in-depth interviews were conducted to
      document in detail the experiences of violence encountered by the abused women.
      Among the 226 women interviewed in the survey, about 84% reported ever having
      experienced at least one act of emotional abuse, physical, or sexual violence
      from their partner during their lifetime. Women who were older (aged above 32
      years), separated, and members of economic/savings group were more likely to
      report ever having experienced any IPV than women with disabilities who were
      younger (aged 32 years and less), married, and not members of economic/savings
      group. Most of the women experiencing violence reported sufferings from physical
      and psychological problems. Of all the women who experienced violence, less than
      half (45%) reported seeking support to minimize or avoid violence experiences.
      However, seeking support from informal network such as family and relatives was
      commonly reported by many (81.4%) of them. Study findings suggest that women with
      disabilities who possess poor socio-economic status coupled with economic
      dependency on husbands' income and wide-spread social stigma against disability
      make them vulnerable to IPV. Future interventions to address IPV against women
      with disabilities should include building community knowledge of disability and
      IPV, countering the pervasive social stigma against disabilities, and improving
      the socio-economic conditions of women with disabilities through education and
      employment. 

PMID- 24860078
TI  - Examining the impact of disability status on intimate partner violence
      victimization in a population sample.
AB  - This study examined effects of impairments in physical and mental health on the
      risk of intimate partner violence (IPV) victimization in a nationally
      representative sample of U.S. adults (>=18 years). A total of 34,563 adults
      completed interviews in two waves of the National Epidemiologic Survey on Alcohol
      and Related Conditions (NESARC). Physical and mental health impairments, as well
      as IPV victimization, were assessed using validated surveys in the total sample
      and by gender. In the total sample, physical health impairments at Wave 1 (odds
      ratio [OR] = 1.22, 95% confidence interval [CI] = [1.04, 1.42], p < .05) and
      mental health impairments at Wave 1 (OR = 1.67, 95% CI = [1.45, 1.91], p < .001)
      were significantly associated with higher risk of IPV victimization at Wave 2,
      compared with those without reported impairments. Higher risk of later IPV
      victimization was also seen among females who reported physical health
      impairments (OR = 1.26, 95% CI [1.04, 1.53], p < .05) and mental health
      impairments (OR = 1.93, 95% CI = [1.63, 2.28], p < .001) compared with those who
      did not report similar limitations. Among males, higher risk of IPV victimization
      was significantly associated with mental health impairments (OR = 1.48, 95% CI =
      [1.19, 1.82], p < .001), compared with those without mental health impairments.
      Adults with physical and mental health impairments may benefit from targeted
      interventions aimed at preventing IPV. 

PMID- 24860079
TI  - The effect of brief, passive psychoeducation on knowledge and ratings of intimate
      partner violence in the United States and Argentina.
AB  - This study explored the benefits of brief, passive psychoeducation about intimate
      partner violence (IPV) in two diverse samples. Participants were 100 college
      students from the United States and Argentina. The experimental group received
      brief psychoeducation about IPV, whereas control subjects did not. Results
      indicated that participants receiving brief, passive psychoeducation did
      significantly better on a subsequent IPV knowledge quiz and were significantly
      more likely to label IPV scenarios as abusive than participants in the control
      group. Mean differences were largest for the more subtle forms of IPV (e.g.,
      social and economic abuse). In contrast, mean differences were negligible for
      physical and sexual abuse, in part because nearly all participants saw these acts
      as abusive regardless of condition. There were no significant differences in
      knowledge improvement as a function of cultural group. Prevention and
      intervention efforts are discussed. 

PMID- 24860080
TI  - Symptoms of post-traumatic stress disorder among battered women in Lebanon: an
      exploratory study.
AB  - Intimate partner violence against women is common in Lebanon and can lead to
      major health problems. However, the incidence of symptoms of post-traumatic
      stress disorder (PTSD) in battered women has not been extensively explored in the
      Lebanese cultural context. The objectives of this study were as follows: (a) to
      determine the prevalence of PTSD symptoms among women in Lebanon who have been
      physically abused by their partners, (b) to assess whether the rate of PTSD
      symptoms varied according to sociodemographic variables, and (c) to reveal other
      attributes that might be risk factors for developing symptoms of PTSD. Of the 95
      physically abused women who met inclusion criteria, 85 completed a questionnaire
      including sociodemographic questions, the physical abuse subscale of the
      Composite Abuse Scale (CAS), and the PTSD Checklist-Civilian Version (PCL-C).
      Results showed a high prevalence of PTSD symptoms (97%), positively correlated
      with physical violence (r = .719). Lower education level and recent abuse were
      correlated with symptom severity, as were the number of problematic habitual
      behaviors in the abusive partner and the use of psychotherapy. Increased
      involvement of health care professionals in the detection of women at risk, with
      referral to appropriate resources, is suggested to improve prevention and
      management efforts. 

PMID- 24860081
TI  - Acquaintance molestation and youth-serving organizations.
AB  - This article is based not only on the research literature but also on the
      extensive field experience of the authors in consulting with investigators,
      attorneys, and organizations on the prevention, investigation, prosecution, and
      civil litigation of molestation of children within or in connection with youth
      serving organizations. Acquaintance molesters have often pursued careers or
      sought out paid or volunteer work with organizations through which they can meet
      children. To address the problem of such offenders, it is necessary for youth
      serving organizations to recognize the diversity of sexual activity, the
      phenomena of "nice-guy" offenders and compliant child victims, and the
      grooming/seduction process, each of which is reviewed here. The four most
      important protection practices for organizations are screening; management, and
      supervision; response to suspicions, allegations, and complaints; and prevention
      and awareness programs. The authors recommend general approaches to each of these
      and describe the reasons many organizations resist implementing available
      preventive measures. 

PMID- 24860082
TI  - How youth-serving organizations enable acquaintance molesters.
AB  - In recent years, some of the country's most prominent institutions have been
      ensnared in child sex abuse scandals. While each abuse incident features its own
      particular circumstances, institutions that have been the subject of these
      scandals have displayed similar patterns of organizational behavior that allowed
      molesting to occur and molesters to escape accountability. We can learn from
      those patterns to better understand and combat acquaintance molestation in youth
      serving organizations. Although sex abuse is an inherent risk in youth work,
      American youth-serving organizations have responded to this risk largely on a
      case-by-case basis after abuse incidents have been revealed, rather than through
      proactive strategies to reduce the risk of abuse and to respond effectively to
      allegations. An examination of abuse scandals reveals common patterns of behavior
      among paid and volunteer staff in organizations that did not enact comprehensive,
      proactive strategies: Faith in the organiation blinded staff to the liklihood of
      abuse; organizations kept workers ignorant about the extent of the abuse problem;
      when abuse accusations arose, staff gave the benefit of the doubt to the adult;
      when abuse accusations were confirmed, staffers did not know how to respond; and
      not knowing how to resopnd, staff prioritized the protection of the organization.
      As a result, child molesters have been falsely exonerated or not held
      accountable, abused children have been disbelieved, and abuse has continued.
      These organizations inadvertently achieved the opposite of their missions: They
      enabled child molesters at the expense of children. 

PMID- 24860083
TI  - Commentary introduction: acquaintance molestation and youth-serving
      organizations.

PMID- 24860084
TI  - Narcissists' social pain seen only in the brain.
AB  - Narcissism is a complex phenomenon, involving a level of defensive self
      enhancement. Narcissists have avoidant attachment styles, maintain distance in
      relationships and claim not to need others. However, they are especially
      sensitive to others' evaluations, needing positive reflected appraisals to
      maintain their inflated self-views, and showing extreme responses (e.g.
      aggression) when rejected. The current study tested the hypothesis that
      narcissists also show hypersensitivity in brain systems associated with distress
      during exclusion. We measured individual differences in narcissism (Narcissistic
      Personality Inventory) and monitored neural responses to social exclusion
      (Cyberball). Narcissism was significantly associated with activity in an a priori
      anatomically defined social pain network (anterior insula, dorsal anterior
      cingulate cortex and subgenual anterior cingulate cortex) during social
      exclusion. Results suggest hypersensitivity to exclusion in narcissists may be a
      function of hypersensitivity in brain systems associated with distress, and
      suggests a potential pathway that connects narcissism to negative consequences
      for longer-term physical and mental health-findings not apparent with self-report
      alone. 

PMID- 24860085
TI  - Pietro Manni (1778-1839) and the care of the apparently dead in the Age of
      Positivism.
AB  - When can a man be declared 'really dead'? Being able to determine whether an
      individual's life has ended or not implies two important considerations, whether
      we can resuscitate him and avoid premature burial, the fear of which is termed
      'taphophobia'. By the end of the 18th century, several scientists were involved
      in the study of apparent death and resuscitation. Pietro Manni was an
      obstetrician who, affected by his brother's death and his inability to help him,
      devoted himself to the study of apparent death, which became his aim in life. His
      Practical handbook for the care of the apparently dead is a detailed essay on
      resuscitation with a precise arrangement of topics - ventilation, tracheostomy,
      electricity and asphyxia in newborns - organised into chapters and paragraphs
      that resemble current texts on resuscitation. 

PMID- 24860086
TI  - Sir Harold Ridley (1906-2001): televising and filming ophthalmic surgery and eye
      examinations.
AB  - Sir Harold Ridley is well known for his pioneering intraocular lens implantation
      surgery. He also had a significant commitment to the televising and filming of
      surgery. In his 1950 Television in Ophthalmology paper, Ridley describes the
      techniques he used to capture his surgery in monochrome and later in full colour
      for audiences at St Thomas' Hospital. 

PMID- 24860089
TI  - Neuroligin 1 induces blood vessel maturation by cooperating with the alpha6
      integrin.
AB  - The synaptic protein Neuroligin 1 (NLGN1), a cell adhesion molecule, is critical
      for the formation and consolidation of synaptic connectivity and is involved in
      vascular development. The mechanism through which NLGN1 acts, especially in
      vascular cells, is unknown. Here, we aimed at deepening our knowledge on the
      cellular activities and molecular pathways exploited by endothelial NLGN1 both in
      vitro and in vivo. We analyzed the phenotypic consequences of NLGN1 expression
      modulation in endothelial cells through in vitro angiogenesis assays and the
      mouse postnatal retinal angiogenesis model. We demonstrate that NLGN1, whereas
      not affecting endothelial cell proliferation or migration, modulates cell
      adhesion to the vessel stabilizing protein laminin through cooperation with the
      alpha6 integrin, a specific laminin receptor. Finally, we show that in vivo,
      NLGN1 and alpha6 integrin preferentially colocalize in the mature retinal
      vessels, whereas NLGN1 deletion causes an aberrant VE-cadherin, laminin and
      alpha6 integrin distribution in vessels, along with significant structural
      defects in the vascular tree. 

PMID- 24860088
TI  - Genetic regulation of mouse liver metabolite levels.
AB  - We profiled and analyzed 283 metabolites representing eight major classes of
      molecules including Lipids, Carbohydrates, Amino Acids, Peptides, Xenobiotics,
      Vitamins and Cofactors, Energy Metabolism, and Nucleotides in mouse liver of 104
      inbred and recombinant inbred strains. We find that metabolites exhibit a wide
      range of variation, as has been previously observed with metabolites in blood
      serum. Using genome-wide association analysis, we mapped 40% of the quantified
      metabolites to at least one locus in the genome and for 75% of the loci mapped we
      identified at least one candidate gene by local expression QTL analysis of the
      transcripts. Moreover, we validated 2 of 3 of the significant loci examined by
      adenoviral overexpression of the genes in mice. In our GWAS results, we find that
      at significant loci the peak markers explained on average between 20 and 40% of
      variation in the metabolites. Moreover, 39% of loci found to be regulating liver
      metabolites in mice were also found in human GWAS results for serum metabolites,
      providing support for similarity in genetic regulation of metabolites between
      mice and human. We also integrated the metabolomic data with transcriptomic and
      clinical phenotypic data to evaluate the extent of co-variation across various
      biological scales. 

PMID- 24860090
TI  - Role of glucocorticoid-induced leucine zipper (GILZ) in bone acquisition.
AB  - Glucocorticoids (GCs) have both anabolic and catabolic effects on bone. However,
      no GC anabolic effect mediator has been identified to date. Here we show that
      targeted expression of glucocorticoid-induced leucine zipper (GILZ), a GC anti
      inflammatory effect mediator, enhances bone acquisition in mice. Transgenic mice,
      in which the expression of GILZ is under the control of a 3.6-kb rat type I
      collagen promoter, exhibited a high bone mass phenotype with significantly
      increased bone formation rate and osteoblast numbers. The increased osteoblast
      activity correlates with enhanced osteogenic differentiation and decreased
      adipogenic differentiation of bone marrow stromal cell cultures in vitro. In line
      with these changes, the mRNA levels of key osteogenic regulators (Runx2 and Osx)
      increased, and the level of adipogenic regulator peroxisome proliferator
      activated receptor (PPAR) gamma2 decreased significantly. We also found that GILZ
      physically interacts with C/EBPs and disrupts C/EBP-mediated PPARgamma gene
      transcription. In conclusion, our results showed that GILZ is capable of
      increasing bone acquisition in vivo, and this action is mediated via a mechanism
      involving the inhibition of PPARgamma gene transcription and shifting of bone
      marrow MSC/progenitor cell lineage commitment in favor of the osteoblast pathway.

PMID- 24860087
TI  - Identifying gene-environment interactions in schizophrenia: contemporary
      challenges for integrated, large-scale investigations.
AB  - Recent years have seen considerable progress in epidemiological and molecular
      genetic research into environmental and genetic factors in schizophrenia, but
      methodological uncertainties remain with regard to validating environmental
      exposures, and the population risk conferred by individual molecular genetic
      variants is small. There are now also a limited number of studies that have
      investigated molecular genetic candidate gene-environment interactions (G * E),
      however, so far, thorough replication of findings is rare and G * E research
      still faces several conceptual and methodological challenges. In this article, we
      aim to review these recent developments and illustrate how integrated, large
      scale investigations may overcome contemporary challenges in G * E research,
      drawing on the example of a large, international, multi-center study into the
      identification and translational application of G * E in schizophrenia. While
      such investigations are now well underway, new challenges emerge for G * E
      research from late-breaking evidence that genetic variation and environmental
      exposures are, to a significant degree, shared across a range of psychiatric
      disorders, with potential overlap in phenotype. 

PMID- 24860092
TI  - Prions and prion-like proteins.
AB  - Prions are self-replicating protein aggregates and are the primary causative
      factor in a number of neurological diseases in mammals. The prion protein (PrP)
      undergoes a conformational transformation leading to aggregation into an
      infectious cellular pathogen. Prion-like protein spreading and transmission of
      aggregates between cells have also been demonstrated for other proteins
      associated with Alzheimer disease and Parkinson disease. This protein-only
      phenomenon may therefore have broader implications in neurodegenerative
      disorders. The minireviews in this thematic series highlight the recent advances
      in prion biology and the roles these unique proteins play in disease. 

PMID- 24860091
TI  - Intact functional fourteen-subunit respiratory membrane-bound [NiFe]-hydrogenase
      complex of the hyperthermophilic archaeon Pyrococcus furiosus.
AB  - The archaeon Pyrococcus furiosus grows optimally at 100  degrees C by converting
      carbohydrates to acetate, CO2, and H2, obtaining energy from a respiratory
      membrane-bound hydrogenase (MBH). This conserves energy by coupling H2 production
      to oxidation of reduced ferredoxin with generation of a sodium ion gradient. MBH
      is encoded by a 14-gene operon with both hydrogenase and Na(+)/H(+) antiporter
      modules. Herein a His-tagged MBH was expressed in P. furiosus and the detergent
      solubilized complex purified under anaerobic conditions by affinity
      chromatography. Purified MBH contains all 14 subunits by electrophoretic analysis
      (13 subunits were also identified by mass spectrometry) and had a measured
      iron:nickel ratio of 15:1, resembling the predicted value of 13:1. The as
      purified enzyme exhibited a rhombic EPR signal characteristic of the ready nickel
      boron state. The purified and membrane-bound forms of MBH both preferentially
      evolved H2 with the physiological donor (reduced ferredoxin) as well as with
      standard dyes. The O2 sensitivities of the two forms were similar (half-lives of
      ~ 15 h in air), but the purified enzyme was more thermolabile (half-lives at 90 
      degrees C of 1 and 25 h, respectively). Structural analysis of purified MBH by
      small angle x-ray scattering indicated a Z-shaped structure with a mass of 310
      kDa, resembling the predicted value (298 kDa). The angle x-ray scattering
      analyses reinforce and extend the conserved sequence relationships of group 4
      enzymes and complex I (NADH quinone oxidoreductase). This is the first report on
      the properties of a solubilized form of an intact respiratory MBH complex that is
      proposed to evolve H2 and pump Na(+) ions.

PMID- 24860093
TI  - Platelet-derived growth factor beta-receptor, transforming growth factor beta
      type I receptor, and CD44 protein modulate each other's signaling and stability.
AB  - Growth factors, such as platelet-derived growth factor BB (PDGF-BB) and
      transforming growth factor beta (TGFbeta), are key regulators of cellular
      functions, including proliferation, migration, and differentiation. Growth factor
      signaling is modulated by context-dependent cross-talk between different
      signaling pathways. We demonstrate in this study that PDGF-BB induces
      phosphorylation of Smad2, a downstream mediator of the canonical TGFbeta pathway,
      in primary dermal fibroblasts. The PDGF-BB-mediated Smad2 phosphorylation was
      dependent on the kinase activities of both TGFbeta type I receptor (TbetaRI) and
      PDGF beta-receptor (PDGFRbeta), and it was prevented by inhibitory antibodies
      against TGFbeta. Inhibition of the activity of the TbetaRI kinase greatly reduced
      the PDGF-BB-dependent migration in dermal fibroblasts. Moreover, we demonstrate
      that the receptors for PDGF-BB and TGFbeta interact physically in primary dermal
      fibroblasts and that stimulation with PDGF-BB induces internalization not only of
      PDGFRbeta but also of TbetaRI. In addition, silencing of PDGFRbeta by siRNA
      decreased the stability of TbetaRI and delayed TGFbeta-induced signaling. We
      further show that the hyaluronan receptor CD44 interacts with both PDGFRbeta and
      TbetaRI. Depletion of CD44 by siRNA increased signaling via PDGFRbeta and TbetaRI
      by stabilizing the receptor proteins. Our data suggest that cross-talk between
      PDGFRbeta and TbetaRI occurs in dermal fibroblasts and that CD44 negatively
      modulates signaling via these receptors. 

PMID- 24860094
TI  - Structure of the Acinetobacter baumannii dithiol oxidase DsbA bound to elongation
      factor EF-Tu reveals a novel protein interaction site.
AB  - The multidrug resistant bacterium Acinetobacter baumannii is a significant cause
      of nosocomial infection. Biofilm formation, that requires both disulfide bond
      forming and chaperone-usher pathways, is a major virulence trait in this
      bacterium. Our biochemical characterizations show that the periplasmic A.
      baumannii DsbA (AbDsbA) enzyme has an oxidizing redox potential and dithiol
      oxidase activity. We found an unexpected non-covalent interaction between AbDsbA
      and the highly conserved prokaryotic elongation factor, EF-Tu. EF-Tu is a
      cytoplasmic protein but has been localized extracellularly in many bacterial
      pathogens. The crystal structure of this complex revealed that the EF-Tu switch I
      region binds to the non-catalytic surface of AbDsbA. Although the physiological
      and pathological significance of a DsbA/EF-Tu association is unknown, peptides
      derived from the EF-Tu switch I region bound to AbDsbA with submicromolar
      affinity. We also identified a seven-residue DsbB-derived peptide that bound to
      AbDsbA with low micromolar affinity. Further characterization confirmed that the
      EF-Tu- and DsbB-derived peptides bind at two distinct sites. These data point to
      the possibility that the non-catalytic surface of DsbA is a potential substrate
      or regulatory protein interaction site. The two peptides identified in this work
      together with the newly characterized interaction site provide a novel starting
      point for inhibitor design targeting AbDsbA. 

PMID- 24860095
TI  - Mouse models for studying the formation and propagation of prions.
AB  - Prions are self-propagating protein conformers that cause a variety of
      neurodegenerative disorders in humans and animals. Mouse models have played key
      roles in deciphering the biology of prions and in assessing candidate
      therapeutics. The development of transgenic mice that form prions spontaneously
      in the brain has advanced our understanding of sporadic and genetic prion
      diseases. Furthermore, the realization that many proteins can become prions has
      necessitated the development of mouse models for assessing the potential
      transmissibility of common neurodegenerative diseases. As the universe of prion
      diseases continues to expand, mouse models will remain crucial for interrogating
      these devastating illnesses. 

PMID- 24860097
TI  - Synthesis of high titer infectious prions with cofactor molecules.
AB  - Recently, synthetic prions with a high level of specific infectivity have been
      produced from chemically defined components in vitro. A major insight arising
      from these studies is that various classes of host-encoded cofactor molecules
      such as phosphatidylethanolamine and RNA molecules are required to form and
      maintain the specific conformation of infectious prions. Synthetic mouse prions
      formed with phosphatidylethanolamine exhibit levels of specific infectivity ~1
      million-fold greater than "protein-only" prions (Deleault, N. R., Walsh, D. J.,
      Piro, J. R., Wang, F., Wang, X., Ma, J., Rees, J. R., and Supattapone, S. (2012)
      Proc. Natl. Acad. Sci. U.S.A. 109, E1938-E1946). Moreover, cofactor molecules
      also appear to regulate prion strain properties by limiting the potential
      conformations of the prion protein (see Deleault et al. above). The production of
      fully infectious synthetic prions provides new opportunities to study the
      mechanism of prion infectivity directly by structural and biochemical methods. 

PMID- 24860096
TI  - Yeast phosphofructokinase-1 subunit Pfk2p is necessary for pH homeostasis and
      glucose-dependent vacuolar ATPase reassembly.
AB  - V-ATPases are conserved ATP-driven proton pumps that acidify organelles. Yeast V
      ATPase assembly and activity are glucose-dependent. Glucose depletion causes V
      ATPase disassembly and its inactivation. Glucose readdition triggers reassembly
      and resumes proton transport and organelle acidification. We investigated the
      roles of the yeast phosphofructokinase-1 subunits Pfk1p and Pfk2p for V-ATPase
      function. The pfk1Delta and pfk2Delta mutants grew on glucose and assembled wild
      type levels of V-ATPase pumps at the membrane. Both phosphofructokinase-1
      subunits co-immunoprecipitated with V-ATPase in wild-type cells; upon deletion of
      one subunit, the other subunit retained binding to V-ATPase. The pfk2Delta cells
      exhibited a partial vma growth phenotype. In vitro ATP hydrolysis and proton
      transport were reduced by 35% in pfk2Delta membrane fractions; they were normal
      in pfk1Delta. In vivo, the pfk1Delta and pfk2Delta vacuoles were alkalinized and
      the cytosol acidified, suggestive of impaired V-ATPase proton transport. Overall
      the pH alterations were more dramatic in pfk2Delta than pfk1Delta at steady state
      and after readdition of glucose to glucose-deprived cells. Glucose-dependent
      reassembly was 50% reduced in pfk2Delta, and the vacuolar lumen was not acidified
      after reassembly. RAVE-assisted glucose-dependent reassembly and/or glucose
      signals were disturbed in pfk2Delta. Binding of disassembled V-ATPase (V1 domain)
      to its assembly factor RAVE (subunit Rav1p) was 5-fold enhanced, indicating that
      Pfk2p is necessary for V-ATPase regulation by glucose. Because Pfk1p and Pfk2p
      are necessary for V-ATPase proton transport at the vacuole in vivo, a role for
      glycolysis at regulating V-ATPase proton transport is discussed. 

PMID- 24860098
TI  - Bacterial RTX toxins allow acute ATP release from human erythrocytes directly
      through the toxin pore.
AB  - ATP is as an extracellular signaling molecule able to amplify the cell lysis
      inflicted by certain bacterial toxins including the two RTX toxins alpha
      hemolysin (HlyA) from Escherichia coli and leukotoxin A (LtxA) from
      Aggregatibacter actinomycetemcomitans. Inhibition of P2X receptors completely
      blocks the RTX toxin-induced hemolysis over a larger concentration range. It is,
      however, at present not known how the ATP that provides the amplification is
      released from the attacked cells. Here we show that both HlyA and LtxA trigger
      acute release of ATP from human erythrocytes that preceded and were not caused by
      cell lysis. This early ATP release did not occur via previously described ATP
      release pathways in the erythrocyte. Both HlyA and LtxA were capable of
      triggering ATP release in the presence of the pannexin 1 blockers carbenoxolone
      and probenecid, and the HlyA-induced ATP release was found to be similar in
      erythrocytes from pannexin 1 wild type and knock-out mice. Moreover, the voltage
      dependent anion channel antagonist TRO19622 had no effect on ATP release by
      either of the toxins. Finally, we showed that both HlyA and LtxA were able to
      release ATP from ATP-loaded lipid (1-palmitoyl-2-oleoyl-phosphatidylcholine)
      vesicles devoid of any erythrocyte channels or transporters. Again we were able
      to show that this happened in a non-lytic fashion, using calcein-containing
      vesicles as controls. These data show that both toxins incorporate into lipid
      vesicles and allow ATP to be released. We suggest that both toxins cause acute
      ATP release by letting ATP pass the toxin pores in both human erythrocytes and
      artificial membranes. 

PMID- 24860099
TI  - Prion-like properties of Tau protein: the importance of extracellular Tau as a
      therapeutic target.
AB  - Work over the past 4 years indicates that multiple proteins associated with
      neurodegenerative diseases, especially Tau and alpha-synuclein, can propagate
      aggregates between cells in a prion-like manner. This means that once an
      aggregate is formed it can escape the cell of origin, contact a connected cell,
      enter the cell, and induce further aggregation via templated conformational
      change. The prion model predicts a key role for extracellular protein aggregates
      in mediating progression of disease. This suggests new therapeutic approaches
      based on blocking neuronal uptake of protein aggregates and promoting their
      clearance. This will likely include therapeutic antibodies or small molecules,
      both of which can be developed and optimized in vitro prior to preclinical
      studies. 

PMID- 24860100
TI  - Prions: generation and spread versus neurotoxicity.
AB  - Neurodegenerative diseases are characterized by the aggregation of misfolded
      proteins in the brain. Among these disorders are the prion diseases, which are
      transmissible, and in which the misfolded proteins ("prions") are also the
      infectious agent. Increasingly, it appears that misfolded proteins in Alzheimer
      and Parkinson diseases and the tauopathies also propagate in a "prion-like"
      manner. However, the association between prion formation, spread, and
      neurotoxicity is not clear. Recently, we showed that in prion disease, protein
      misfolding leads to neurodegeneration through dysregulation of generic
      proteostatic mechanisms, specifically, the unfolded protein response. Genetic and
      pharmacological manipulation of the unfolded protein response was neuroprotective
      despite continuing prion replication, hence dissociating this from neurotoxicity.
      The data have clear implications for treatment across the spectrum of these
      disorders, targeting pathogenic processes downstream of protein misfolding. 

PMID- 24860102
TI  - Comparison of two Gram stain point-of-care systems for urogenital gonorrhoea
      among high-risk patients: diagnostic accuracy and cost-effectiveness before and
      after changing the screening algorithm at an STI clinic in Amsterdam.
AB  - OBJECTIVES: To compare point-of-care (POC) systems in two different periods: (1)
      before 2010 when all high-risk patients were offered POC management for
      urogenital gonorrhoea by Gram stain examination; and (2) after 2010 when only
      those with symptoms were offered Gram stain examination. METHODS: Retrospective
      comparison of a Gram stain POC system to all high-risk patients (2008-2009) with
      only those with urogenital symptoms (2010-2011) on diagnostic accuracy, loss to
      follow-up, presumptively and correctly treated infections and diagnostic costs.
      Culture was the reference diagnostic method. RESULTS: In men the sensitivity of
      the Gram stain was 95.9% (95% CI 93.1% to 97.8%) in 2008-2009 and 95.4% (95% CI
      93.7% to 96.8%) in 2010-2011, and in women the sensitivity was 32.0% (95% CI
      19.5% to 46.7%) and 23.1% (95% CI 16.1% to 31.3%), respectively. In both periods
      the overall specificity was high (99.9% (95% CI 99.8% to 100%) and 99.8% (95% CI
      99.7% to 99.9%), respectively). The positive predictive value (PPV) and negative
      predictive value (NPV) before and after 2010 were also high: PPV 97.0% (95% CI
      94.5% to 98.5%) and 97.7% (95% CI 96.3% to 98.6%), respectively; NPV 99.6% (95%
      CI 99.4% to 99.7%) and 98.8% (95% CI 98.5% to 99.0%), respectively. There were no
      differences between the two time periods in loss to follow-up (7.1% vs 7.0%).
      Offering Gram stains only to symptomatic high-risk patients as opposed to all
      high-risk patients saved ?2.34 per correctly managed consultation (a reduction of
      7.7%). CONCLUSIONS: The sensitivity of the Gram stain is high in men but low in
      women. When offered only to high-risk patients with urogenital symptoms, the cost
      per correctly managed consultation is reduced by 7.7% without a significant
      difference in accuracy and loss to follow-up.

PMID- 24860103
TI  - Sexual risk typologies and their relationship with early parenthood and STI
      outcomes among urban African-American emerging adults: a cross-sectional latent
      profile analysis.
AB  - OBJECTIVES: Identifying sexual risk patterns associated with HIV/sexually
      transmitted infections (STI) and early parenthood within population subgroups is
      critical for targeting risk reduction interventions. METHODS: Latent Class
      Analysis (LCA) was used to identify sexual behaviour typologies to predict sexual
      risk outcomes among 274 (63% female) unmarried, sexually active African-American
      emerging adults (M age=19.31 years) living in disadvantaged urban neighbourhoods.
      Participants were enrolled in a larger cross-sectional observational study of
      risk and protective behaviours. LCA defined membership into discrete risk classes
      based on reported sex risk behaviours. RESULTS: Three groups were identified: The
      'low contraception use' risk class (32%) had low rates of condom or other birth
      control use, moderate rates of sexual initiation before age 16 years, and the
      highest pregnancy/early parenthood and STI rates. The predominately male 'early
      sex' risk class (32%) had higher rates of early initiation and multiple partners,
      risks that were countered by higher contraception and condom use. Both these risk
      groups showed higher probability to use substances before sex relative to the
      'low sex risk' class (36%), which showed low rates on all risk behaviours.
      CONCLUSIONS: LCA identified distinct risk clusters that predicted sexual health
      outcomes and can inform targeted interventions for a minority youth population
      disproportionately affected by HIV, other STIs, and early parenthood.

PMID- 24860104
TI  - The application of capillary electrophoresis in the determination of glutathione
      in healthy women's blood.
AB  - The purpose of this work was to compare glutathione status in the blood of women
      taking oral contraceptives, female smokers and pregnant women using both the
      capillary electrophoresis (CE) and alloxan methods. The studies were performed on
      the whole blood prepared by deproteinization by 25% metaphosphoric acid. The
      reduced glutathione (GSH) was measured by alloxan and CE methods. Oxidized
      glutathione (GSSG) was measured by CE and the GSH/GSSG ratio was calculated. In
      pregnant women (Group A), women taking oral contraceptives (Group B) and female
      smokers (Group C), lower concentrations of GSH were observed compared with the
      control group (Group D) as measured by CE and alloxan methods, suggesting the
      presence of oxidative stress. The level of GSSG in Group C was higher than in
      Group D, indicating glutathione oxidation. In Groups A and B, reduced levels of
      GSSG were observed, which indicates that other processes besides oxidation affect
      glutathione status. In Groups A and C, a lower GSH/GSSG ratio was observed than
      in Group D, while in Group B no statistical change was observed. In conclusion,
      the advantage of CE is the possibility of measuring GSSG, which could allow for a
      more accurate interpretation of the status of GSH in the human body. Oxidation of
      glutathione in female smokers was indicated, while in pregnant women and women
      taking oral contraceptives processes other than oxidation can be associated with
      a decrease in glutathione levels. 

PMID- 24860101
TI  - The molecular basis of ligand interaction at free fatty acid receptor 4
      (FFA4/GPR120).
AB  - The long-chain fatty acid receptor FFA4 (previously GPR120) is receiving
      substantial interest as a novel target for the treatment of metabolic and
      inflammatory disease. This study examines for the first time the detailed mode of
      binding of both long-chain fatty acid and synthetic agonist ligands at FFA4 by
      integrating molecular modeling, receptor mutagenesis, and ligand structure
      activity relationship approaches in an iterative format. In doing so, residues
      required for binding of fatty acid and synthetic agonists to FFA4 have been
      identified. This has allowed for the refinement of a well validated model of the
      mode of ligand-FFA4 interaction that will be invaluable in the identification of
      novel ligands and the future development of this receptor as a therapeutic
      target. The model reliably predicted the effects of substituent variations on
      agonist potency, and it was also able to predict the qualitative effect of
      binding site mutations in the majority of cases. 

PMID- 24860105
TI  - A comparison of protein profiles of cervical tissue homogenate, exfoliated cells
      from cervix and serum in normal and cervical malignancy conditions.
AB  - Cervical cancer, the second most common cancer in women, progresses silently over
      long periods before producing any clinical manifestation. Research in early
      detection of this condition using proteomic techniques is of very recent origin.
      We used high-performance liquid chromatography combined with laser-induced
      fluorescence method in our lab to record the protein profiles of tissue
      homogenate, cell lysate and serum samples of normal and different stages of
      malignant conditions of the cervix. Information on protein markers in the protein
      profiles was derived using various data processing methods including curve
      resolution. The variations in relative intensities of different peaks with
      respect to peak height, width and area under the curve from different sample
      types were compared to get information regarding the concentration of the various
      proteins and their significance in the induction and metastasis of cervical
      cancer. The method can be used in diagnosis, follow-up with respect to the
      progression, remission and effective therapy, in cervical malignancy. 

PMID- 24860106
TI  - Fecal overflow often affects children with chronic constipation that appears
      after the age of 2 years.
AB  - Chronic functional constipation with or without encopresis is a common problem in
      the pediatric population, and the prevalence of encopresis may be underestimated.
      The aim of this study was to assess the prevalence and risk factors for overflow
      incontinence in patients with chronic constipation seen at a pediatric
      gastroenterology consultation. A retrospective study of 270 files of patients
      seen between 1997 and 2012 was conducted, and a classification according to Rome
      III criteria was done. Among 145 (53.7%) boys and 125 (46.2%) girls, 117 had
      overflow incontinence (43.3%) - 41 (35%) girls and 76 (65%) boys. The first
      symptoms of chronic constipation appeared at a median age of 30 and 33 months in
      encopretic and 16 and 12 months in nonencopretic girls and boys, respectively.
      The first specialized consultation took place after a median disease duration of
      26.5 and 24 months in encopretic and 16 and 9 months in nonencopretic girls and
      boys, respectively. A history of stool retention and the presence of scybala at
      examination, but not of pain at defecation or anal fissure, were associated with
      encopresis. The onset of chronic constipation after the age of 2 years, a longer
      disease duration, male gender, and a history of stool retention were seen as risk
      factors for the development of encopresis in patients with chronic functional
      constipation.

PMID- 24860108
TI  - Fulvimonas yonginensis sp. nov., isolated from greenhouse soil, and emended
      description of the genus Fulvimonas.
AB  - A novel strain, designated 5GHs31-2(T), was isolated from a greenhouse soil
      sample collected from Yongin city, South Korea. Cells of strain 5GHs31-2(T) were
      Gram-stain-negative, rod-shaped, polar flagellated and yellow-pigmented. The
      isolate was aerobic, catalase-negative and oxidase-positive and grew optimally at
      28-30  degrees C and pH 7.0. Strain 5GHs31-2(T) revealed the highest 16S rRNA
      gene sequence similarities with Fulvimonas soli LMG 19981(T) (97.6%), Dyella
      thiooxydans ATSB10(T) (97.5%) and Frateuria terrea VA24(T) (97.4%). Furthermore,
      the neighbour-joining tree showed that strain 5GHs31-2(T) was a representative of
      a member of the genus Fulvimonas. Strain 5GHs31-2(T) contained iso-C(16 : 0),
      summed feature 9 (iso-C(17 : 1)omega9c and/or C(16 : 0) 10-methyl), iso-C(15 : 0)
      and iso-C(17 : 0) as the major fatty acids, phosphatidylethanolamine,
      phosphatidylglycerol, diphosphatidylglycerol and an aminolipid as the main polar
      lipids and Q-8 as the predominant quinone. The genomic DNA G+C content of 5GHs31
      2(T) was 73.0 mol%. According to DNA-DNA hybridization experiments, DNA-DNA
      relatedness values between strain 5GHs31-2(T) and its closest phylogenetic
      neighbours were below 70%. Based on the taxonomic data, strain 5GHs31-2(T)
      represents a novel species of the genus Fulvimonas, for which the name Fulvimonas
      yonginensis sp. nov. is proposed. The type strain is 5GHs31-2(T) ( = KACC
      16952(T) = DSM 28344(T)).

PMID- 24860109
TI  - Proposal of Effusibacillus lacus gen. nov., sp. nov., and reclassification of
      Alicyclobacillus pohliae as Effusibacillus pohliae comb. nov. and
      Alicyclobacillus consociatus as Effusibacillus consociatus comb. nov.
AB  - A novel thermophilic, facultatively anaerobic bacterium, strain skLN1(T), was
      isolated from the sediment of a freshwater lake in Japan. Cells of strain
      skLN1(T) were rod-shaped and Gram-stain-variable. A KOH lysis test suggested that
      the cell wall of the isolate has a Gram-positive structure. For aerobic growth,
      the optimum pH was pH 7.25-7.50 and the optimum temperature was 50-52  degrees C.
      The G+C content of the genomic DNA was 50.8 mol%. Nitrate was reduced to nitrite.
      Alicyclic fatty acids were not detected, and branched-chain fatty acids were
      major components in the cellular fatty acid profile. MK-7 was the predominant
      respiratory quinone. Phylogenetic analysis based on 16S rRNA gene sequences
      revealed that the isolated strain was related most closely to Alicyclobacillus
      consociatus CCUG 53762(T) (95% similarity). This analysis also showed that the
      monophyly of the genus Alicyclobacillus had been lost. On the basis of
      phylogenetic and phenotypic characterization, Effusibacillus lacus gen. nov., sp.
      nov. is proposed. The type strain of Effusibacillus lacus is skLN1(T) ( = NBRC
      109614(T) = DSM 27172(T)). It is also proposed that Alicyclobacillus pohliae and
      Alicyclobacillus consociatus should be reclassified to the genus Effusibacillus
      as Effusibacillus pohliae comb. nov. and Effusibacillus consociatus comb. nov.,
      respectively.

PMID- 24860107
TI  - Sequential actions of the AAA-ATPase valosin-containing protein (VCP)/p97 and the
      proteasome 19 S regulatory particle in sterol-accelerated, endoplasmic reticulum
      (ER)-associated degradation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase.
AB  - Accelerated endoplasmic reticulum (ER)-associated degradation (ERAD) of the
      cholesterol biosynthetic enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase
      results from its sterol-induced binding to ER membrane proteins called Insig-1
      and Insig-2. This binding allows for subsequent ubiquitination of reductase by
      Insig-associated ubiquitin ligases. Once ubiquitinated, reductase becomes
      dislocated from ER membranes into the cytosol for degradation by 26 S proteasomes
      through poorly defined reactions mediated by the AAA-ATPase valosin-containing
      protein (VCP)/p97 and augmented by the nonsterol isoprenoid geranylgeraniol.
      Here, we report that the oxysterol 25-hydroxycholesterol and geranylgeraniol
      combine to trigger extraction of reductase across ER membranes prior to its
      cytosolic release. This conclusion was drawn from studies utilizing a novel assay
      that measures membrane extraction of reductase by determining susceptibility of a
      lumenal epitope in the enzyme to in vitro protease digestion. Susceptibility of
      the lumenal epitope to protease digestion and thus membrane extraction of
      reductase were tightly regulated by 25-hydroxycholesterol and geranylgeraniol.
      The reaction was inhibited by RNA interference-mediated knockdown of either
      Insigs or VCP/p97. In contrast, reductase continued to become membrane-extracted,
      but not cytosolically dislocated, in cells deficient for AAA-ATPases of the
      proteasome 19 S regulatory particle. These findings establish sequential roles
      for VCP/p97 and the 19 S regulatory particle in the sterol-accelerated ERAD of
      reductase that may be applicable to the ERAD of other substrates. 

PMID- 24860110
TI  - Clostridium bornimense sp. nov., isolated from a mesophilic, two-phase,
      laboratory-scale biogas reactor.
AB  - A novel anaerobic, mesophilic, hydrogen-producing bacterium, designated strain
      M2/40(T), was isolated from a mesophilic, two-phase, laboratory-scale biogas
      reactor fed continuously with maize silage supplemented with 5% wheat straw. 16S
      rRNA gene sequence comparison revealed an affiliation to the genus Clostridium
      sensu stricto (cluster I of the clostridia), with Clostridium cellulovorans as
      the closest characterized species, showing 93.8% sequence similarity to the type
      strain. Cells of strain M2/40(T) were rods to elongated filamentous rods that
      showed variable Gram staining. Optimal growth occurred at 35  degrees C and at pH
      7. Grown on glucose, the main fermentation products were H2, CO2, formate,
      lactate and propionate. The DNA G+C content was 29.6 mol%. The major fatty acids
      (>10 %) were C(16 : 0), summed feature 10 (C(18 : 1)omega11c/omega9t/omega6t
      and/or unknown ECL 17.834) and C(18 : 1)omega11c dimethylacetal. Based on
      phenotypic, chemotaxonomic and phylogenetic differences, strain M2/40(T)
      represents a novel species within the genus Clostridium, for which we propose the
      name Clostridium bornimense sp. nov. The type strain is M2/40(T) ( = DSM 25664(T)
      = CECT 8097(T)).

PMID- 24860111
TI  - Bacillus oryzaecorticis sp. nov., a moderately halophilic bacterium isolated from
      rice husks.
AB  - A Gram-stain-positive, aerobic, endospore-forming, moderately halophilic rod,
      designated strain R1(T), was isolated from rice husks and subjected to a
      taxonomic study using a polyphasic approach. Strain R1(T) produced spherical or
      ellipsoidal endospores at a subterminal position in swollen sporangia, and was
      catalase- and oxidase-positive. The isolate grew optimally at 37  degrees C and
      pH 6.0-7.0, and could grow in the presence of up to 9% (w/v) NaCl. Phylogenetic
      analysis based on 16S rRNA gene sequences indicated that strain R1(T) belongs to
      the genus Bacillus. The closest relatives of strain R1(T) were Bacillus subtilis
      subsp. subtilis NCIB 3610(T), Bacillus aquimaris TF-12(T), and Bacillus
      marisflavi TF-11(T), with 16S rRNA gene sequence similarities of 96.0%, 98.4%,
      and 98.7%, respectively. DNA-DNA relatedness values between the isolate and the
      reference strains were <=42+/-3%. The predominant menaquinones were MK-5 (50%)
      and MK-7 (50%). The major polar lipids were phosphatidylglycerol,
      diphosphatidylglycerol, and phosphatidylethanolamine. The major cellular fatty
      acids were iso-C(15 : 0) (48.6%) and anteiso-C(15 : 0) (20.6%), and the cell-wall
      diamino acid was meso-diaminopimelic acid. On the basis of 16S rRNA gene sequence
      analyses and chemotaxonomic and phenotypic characteristics, it is concluded that
      strain R1(T) represents a novel species of the genus Bacillus, for which we
      propose the name Bacillus oryzaecorticis sp. nov. The type strain is R1(T) ( =
      KACC 17217(T) = KCCM 90231(T) = JCM 19602(T)).

PMID- 24860112
TI  - Halopolyspora alba gen. nov., sp. nov., isolated from sediment.
AB  - A novel halophilic, filamentous actinomycete, designated strain AFM 10251(T), was
      isolated from a sediment sample collected from the Dead Sea, Israel. The isolate
      grew with 10-35% multi-salts, and did not grow without NaCl or MgCl2. The isolate
      formed a white aerial mycelium, and long chains of arthrospores with more than 10
      spores per chain. The spores were spherical or oval with warty surfaces, and
      sterile mycelium was present between individual spores. The isolate contained
      meso-diaminopimelic acid and a small proportion of LL-diaminopimelic acid as cell
      wall diamino acids, and galactose and arabinose as whole-cell sugars. The major
      menaquinone was MK-9(H4). The polar lipids were diphosphatidylglycerol,
      phosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine,
      phosphatidylinositol and three unknown phospholipids. Major fatty acids were iso
      C(16 : 0), iso-C(17 : 0), iso-C(15 : 0) and anteiso-C(17 : 0). The DNA G+C
      content of strain AFM 10251(T) was 66.7 mol%. Phylogenetic analysis based on 16S
      rRNA gene sequences showed that strain AFM 10251(T) and the genus Actinopolyspora
      formed a distinct lineage. Analysis of the secondary structures of variable areas
      of the 16S rRNA gene showed that strain AFM 10251(T) was different from all
      recognized species of the genus Actinopolyspora and members of the family
      Pseudonocardiaceae. Analysis of the signature nucleotides of the 16S rRNA gene
      showed that strain AFM 10251(T) and Actinopolyspora halophila formed a single
      group, but with base pair differences at positions 127 : 234 and 183 : 194. On
      the basis of analysis of chemical and molecular characteristics, strain AFM
      10251(T) is considered to represent a novel species of a new genus in the family
      Actinopolysporaceae, for which the name Halopolyspora alba gen. nov., sp. nov. is
      proposed. The type strain of Halopolyspora alba is AFM 10251(T) ( = DSM 45976(T)
      = CGMCC 4.7114(T)).

PMID- 24860113
TI  - Conyzicola lurida gen. nov., sp. nov., isolated from the root of Conyza
      canadensis.
AB  - A novel Gram-stain-positive, non-spore-forming, pale yellow, irregular rod-shaped
      bacterium designated strain HWE2-01(T) was isolated from the surface-sterilized
      root of horseweed (Conyza canadensis). Phylogenetic analysis based on 16S rRNA
      gene sequences revealed that strain HWE2-01(T) belongs to the family
      Microbacteriaceae and showed sequence similarity levels of 97.1-97.7% with
      species of the genus Salinibacterium, 95.9-97.6% with species of the genus
      Leifsonia and 97.1% with Homoserinimonas aerilata. The highest sequence
      similarity (97.7%) was with Salinibacterium xinjiangense 0543(T). The genomic DNA
      G+C content of the novel strain was 68.1 mol%. The predominant cellular fatty
      acid of strain HWE2-01(T) was anteiso-C15 : 0, major menaquinones were MK-10, MK
      9 and MK-11, and diagnostic polar lipids were diphosphatidylglycerol and
      phosphatidylglycerol. The peptidoglycan of the novel strain contained 2,4
      diaminobutyric acid, alanine, glycine and glutamic acid. The cell-wall sugars of
      strain HWE2-01(T) were galactose, mannose and rhamnose. The murein was of the
      acetyl type. Based on the results of the phenotypic and phylogenetic analysis,
      strain HWE2-01(T) differed in some respects from other members of the family
      Microbacteriaceae. Therefore, strain HWE2-01(T) is proposed to represent a novel
      species of a new genus in the family Microbacteriaceae with the name Conyzicola
      lurida gen. nov., sp. nov. (type strain = HWE2-01(T) = KCTC 29231(T) = JCM
      19257(T)).

PMID- 24860114
TI  - Paracoccus lutimaris sp. nov., isolated from a tidal flat sediment.
AB  - A Gram-negative, coccoid or oval-shaped and gliding bacterial strain, designated
      HDM-25(T), belonging to the Alphaproteobacteria, was isolated from a tidal flat
      sediment of the Yellow Sea, Korea, and was subjected to a polyphasic taxonomic
      study. Strain HDM-25(T) grew optimally at pH 7.0-8.0, at 30  degrees C and in the
      presence of 2-3% (w/v) NaCl. Neighbour-joining, maximum-likelihood and maximum
      parsimony phylogenetic trees based on 16S rRNA gene sequences showed that strain
      HDM-25(T) fell within the clade comprising the species of the genus Paracoccus,
      clustering with the type strain of Paracoccus aminophilus, with which it
      exhibited the highest 16S rRNA gene sequence similarity (97.7%). The 16S rRNA
      gene sequence similarity between strain HDM-25(T) and the type strains of the
      other species of Paracoccus was 93.6-97.0%. The DNA G+C content was 65.9 mol% and
      the mean DNA-DNA relatedness between strain HDM-25(T) and the type strain of P.
      aminophilus was 10.7+/-2.7% (9.9+/-4.0%, reciprocal analysis). Strain HDM-25(T)
      contained Q-10 as the predominant ubiquinone and summed feature 8 (C(18 :
      1)omega7c and/or C(18 : 1)omega6c) and C(16 : 0) as the major fatty acids. The
      major polar lipids were phosphatidylcholine, phosphatidylglycerol,
      diphosphatidylglycerol, an unidentified aminolipid, an unidentified glycolipid
      and an unidentified lipid. Differential phenotypic properties, together with the
      phylogenetic and genetic distinctiveness, demonstrated that strain HDM-25(T) is
      distinguishable from other species of the genus Paracoccus. On the basis of the
      data presented, strain HDM-25(T) is considered to represent a novel species of
      the genus Paracoccus, for which the name Paracoccus lutimaris sp. nov. is
      proposed. The type strain is HDM-25(T) ( = KCTC 42007(T) = CECT 8525(T)).

PMID- 24860115
TI  - Spirochaeta psychrophila sp. nov., a psychrophilic spirochaete isolated from
      subseafloor sediment, and emended description of the genus Spirochaeta.
AB  - An obligately anaerobic, psychrophilic spirochaete, strain MO-SPC1(T), was
      isolated from a methanogenic microbial community grown in a continuous-flow
      bioreactor. Originally, this community was obtained from subseafloor sediments
      off the Shimokita Peninsula of Japan in the north-western Pacific Ocean. The
      cells were motile, Gram-stain-negative, helical, 0.25-0.55*3.6-15 um, with a
      wavelength of approximately 0.5-0.6 um. Strain MO-SPC1(T) grew at 0-18  degrees C
      (optimally at 15  degrees C), at pH 6.0-7.5 (optimally at pH 6.8-7.0) and in 20
      70 g NaCl l(-1) (optimally at 30-40 NaCl l(-1)). The strain grew chemo
      organotrophically with mono-, di- and polysaccharides. The major end products of
      glucose fermentation were acetate, ethanol, hydrogen and carbon dioxide. The
      abundant polar lipids of strain MO-SPC1(T) were diphosphatidylglycerol,
      phosphatidylglycerol, unknown phospholipids and an unknown lipid. The major
      cellular fatty acids (>5% of the total) were C(14 : 0), C(16 : 0), iso-C(13 : 0),
      iso-C(14 : 0), iso-C(15 : 0), anteiso-C(13 : 0) and anteiso-C(15 : 0). To the
      best of our knowledge, this is the first report of the fatty acids iso-C(13 : 0)
      and anteiso-C(13 : 0) from a species of the genus Spirochaeta. Isoprenoid
      quinones were not found. The G+C content of the genomic DNA was 39.8 mol%. 16S
      rRNA gene sequence-based phylogenetic analysis showed that strain MO-SPC1(T) was
      affiliated with the genus Spirochaeta, and its closest relatives were Spirochaeta
      isovalerica MA-2(T) (95.6% sequence identity) and Spirochaeta litoralis R1(T)
      (89.4%). Based on its phenotypic characteristics and phylogenetic traits, strain
      MO-SPC1(T) is placed in a separate taxon at the level of a novel species within
      the genus Spirochaeta, for which the name Spirochaeta psychrophila sp. nov. is
      proposed, reflecting its true psychrophilic physiology. The type strain is MO
      SPC1(T) ( = JCM 17280(T) = DSM 23951(T)). To our knowledge, this is the first
      report of an isolate of the phylum Spirochaetes from a deep-sea sedimentary
      environment, and of an obligately psychrophilic nature.

PMID- 24860116
TI  - Delay effects in the response of low-grade gliomas to radiotherapy: a
      mathematical model and its therapeutical implications.
AB  - Low-grade gliomas (LGGs) are a group of primary brain tumours usually encountered
      in young patient populations. These tumours represent a difficult challenge
      because many patients survive a decade or more and may be at a higher risk for
      treatment-related complications. Specifically, radiation therapy is known to have
      a relevant effect on survival but in many cases it can be deferred to avoid side
      effects while maintaining its beneficial effect. However, a subset of LGGs
      manifests more aggressive clinical behaviour and requires earlier intervention.
      Moreover, the effectiveness of radiotherapy depends on the tumour
      characteristics. Recently Pallud et al. (2012. Neuro-Oncology, 14: , 1-10)
      studied patients with LGGs treated with radiation therapy as a first-line therapy
      and obtained the counterintuitive result that tumours with a fast response to the
      therapy had a worse prognosis than those responding late. In this paper, we
      construct a mathematical model describing the basic facts of glioma progression
      and response to radiotherapy. The model provides also an explanation to the
      observations of Pallud et al. Using the model, we propose radiation fractionation
      schemes that might be therapeutically useful by helping to evaluate tumour
      malignancy while at the same time reducing the toxicity associated to the
      treatment. 

PMID- 24860118
TI  - Men's Health Surveillance Systems.

PMID- 24860117
TI  - The role of basophils and proallergic cytokines, TSLP and IL-33, in cutaneously
      sensitized food allergy.
AB  - Cutaneous sensitization with a food antigen before its consumption elicits the
      development of food allergy. Here, we report the site- and stage-dependent roles
      of basophils and proallergic cytokines, thymic stromal lymphopoietin (TSLP) and
      IL-33, in a mouse model of food allergy initially sensitized cutaneously with the
      food antigen. Mice were epicutaneously sensitized with the food antigen ovalbumin
      (OVA) followed by oral challenge with OVA. Epicutaneously sensitized mice
      produced OVA-specific IgE and developed IgE-dependent anaphylaxis after oral
      challenge. Basophil-depleted or TSLP-receptor-deficient mice did not produce OVA
      specific IgE and were protected from oral challenge-induced anaphylaxis. IL-33
      deficient mice produced normal levels of OVA-specific IgE. However, IL-33
      deficient mice and mice treated with recombinant soluble IL-33 receptor were
      protected from anaphylaxis. Thus, basophils and TSLP have pivotal roles in Th2
      development in the skin during the sensitization phase of food allergy. In
      contrast, while IL-33 is dispensable for promoting cutaneous antigen
      sensitization, the cytokine is essential for inducing IgE-dependent anaphylaxis
      in the gut. 

PMID- 24860119
TI  - NKG2D functions as an activating receptor on natural killer cells in the common
      marmoset (Callithrix jacchus).
AB  - The natural killer group 2 membrane D (NKG2D) receptor is an NK-activating
      receptor that plays an important role in host defense against tumors and viral
      infections. Although the marmoset is an important and reliable animal model,
      especially for the study of human-specific viral infections, functional
      characterization of NKG2D on marmoset NK cells has not previously been conducted.
      In the present study, we investigated a subpopulation of marmoset NK cells that
      express NKG2D and exhibit cytolytic potential. On the basis of their CD16 and
      CD56 expression patterns, marmoset NK cells can be classified into three
      subpopulations: CD16(+) CD56(-), CD16(-) CD56(+) and CD16(-) CD56(-) cells. NKG2D
      expression on marmoset CD16(+) CD56(-) and CD16(-) CD56(+) splenocytes was
      confirmed using an NKG2D ligand composed of an MHC class I chain-related molecule
      A (MICA)-Fc fusion protein. When marmoset splenocytes were cultured with IL-2 for
      4 days, NKG2D expression was retained on CD16(+) CD56(-) and CD16(-) CD56(+). In
      addition, CD16(+) CD56(+) cells within the marmoset NK population appeared which
      expressed NKG2D after IL-2 stimulation. IL-2-activated marmoset NK cells showed
      strong cytolytic activity against K562 target cells and target cells stably
      expressing MICA. Further, the cytolytic activity of marmoset splenocytes was
      significantly reduced after addition of MICA-Fc fusion protein. Thus, NKG2D
      functions as an activating receptor on marmoset NK cells that possesses cytotoxic
      potential, and phenotypic profiles of marmoset NK cell subpopulations are similar
      to those seen in humans. 

PMID- 24860120
TI  - Lipopeptides are signaled by Toll-like receptor 1, 2 and 6 in endolysosomes.
AB  - Toll-like receptors (TLRs) recognize a variety of microbial products and induce
      defense responses. Pathogen sensing by TLRs occurs either on the cell surface or
      in endolysosomes. TLR-dependent responses are greatly influenced by the site of
      pathogen sensing. TLR heterodimers TLR1/TLR2 and TLR2/TLR6 recognize tri- or
      diacylated microbial lipopeptides, respectively. Although TLR1, 2 and 6 are
      believed to localize on the cell surface of immune cells, little is known about
      where lipopeptides are signaled. In this study, we established mAbs to TLR1, 2
      and 6. TLR1, 2 and 6 were expressed on the surface of B cells, monocytes and
      dendritic cells in a manner dependent on a TLR-specific chaperone PRAT4A (protein
      associated with TLR4 A). Cell surface localization of TLR1 or TLR6 was not
      necessarily required for TLR2 response. Furthermore, a dynamin inhibitor
      'Dynasore' abolished the lipopeptide responses by preventing lipopeptide
      internalization into LAMP-1 and LAMP-2 positive compartments. Our findings
      suggest that lipopeptides elicit TLR1/2 and TLR2/6 signaling in the
      endolysosomes, but not on the cell surface. 

PMID- 24860121
TI  - Long-term outcome in Japanese patients with lupus nephritis.
AB  - The objective of this study was to clarify the long-term outcome in patients with
      lupus nephritis (LN) according to the International Society of Nephrology and
      Renal Pathology Society classification. This retrospective analysis comprised 186
      Japanese patients given a diagnosis of LN by renal specimen with a mean
      observation period of 12 years. Primary end point was defined as death or end
      stage renal disease, and standardized mortality ratios were calculated. Five
      patients presented with histopathological class I, 62 with II, 21 with III or
      III+V, 73 with IV or IV+V and 25 with V. Fourteen deaths occurred, corresponding
      to an overall standardized mortality ratio of 3.59 (95% confidence interval 2.02
      5.81, p < 0.0001). Kaplan-Meier analysis revealed a 10-year overall survival of
      95.7%. Nephrotic proteinuria (>=3.5 g/day) at baseline was identified as an
      independent poor prognostic factor for overall survival in Cox regression
      analysis. Kaplan-Meier analysis revealed a 10-year renal survival as 94.3%. Male
      gender and nephrotic proteinuria at baseline were identified as independent poor
      prognostic factors for renal survival in Cox regression analysis. In conclusion,
      LN was associated with a 3.59-fold increase in mortality compared with the
      general population. Male gender and nephrotic proteinuria were predictive for
      poor renal outcome. 

PMID- 24860122
TI  - Mediation misgivings: ambiguous clinical and public health interpretations of
      natural direct and indirect effects.
AB  - Recent methodological innovation is giving rise to an increasing number of
      applied papers in medical and epidemiological journals in which natural direct
      and indirect effects are estimated. However, there is a longstanding debate on
      whether such effects are relevant targets of inference in population health. In
      light of the repeated calls for a more pragmatic and consequential epidemiology,
      we review three issues often raised in this debate: (i) the use of composite
      cross-world counterfactuals and the need for cross-world independence
      assumptions; (ii) interventional vs non-interventional identifiability; and (iii)
      the interpretational ambiguity of natural direct and indirect effect estimates.
      We use potential outcomes notation and directed acyclic graphs to explain 'cross
      world' assumptions, illustrate implications of this assumption via regression
      models and discuss ensuing issues of interpretation. We argue that the debate on
      the relevance of natural direct and indirect effects rests on whether one takes
      as a target of inference the mathematical object per se, or the change in the
      world that the mathematical object represents. We further note that public health
      questions may be better served by estimating controlled direct effects. 

PMID- 24860123
TI  - Postscript: research agenda to guide the next generation of public reports for
      consumers.
AB  - There is significant interest in building the next generation of public reporting
      tools that will more effectively engage consumers and better enable them to make
      use of comparative performance information when selecting a provider. Demand for
      public reporting tools that make health care cost and quality information
      transparent is fueled by a variety of market forces underway. A host of public
      reporting efforts and studies have identified a number of challenges,
      highlighting that we still do not understand how best to design public reports to
      meet the needs of the consumer. We identify five areas for additional research
      that, if addressed, could foster better design and delivery of quality and cost
      information to consumers. 

PMID- 24860124
TI  - Evidence-based use of FFP: the influence of a priming strategy without FFP during
      CPB on postoperative coagulation and recovery in pediatric patients.
AB  - OBJECTIVE: Although fresh frozen plasma (FFP) is one of the most commonly used
      hemostatic agents in clinical specialties today, there is little evidence
      available supporting its administration. Our present study observed the effects
      of a priming strategy without FFP during cardiopulmonary bypass (CPB) on
      postoperative coagulation and clinical recovery in pediatric patients, aiming to
      supply new evidence for evidence-based use of FFP. METHOD: Eighty pediatric
      patients with congenital heart disease undergoing cardiac surgery with CPB were
      randomized to receive either 10-20 ml/kg 4% succinylated gelatin (Gelofusine, GEL
      group, n = 40) or 1-2 units FFP (FFP group, n = 40) in the pump prime. Rapid
      thromboelastography (r-TEG) and functional fibrinogen level were measured before
      skin incision and 15 minutes after heparin reversal. We recorded the volume of
      chest tube drainage, transfusion requirements and the dosage of pharmacological
      agents. The ventilation time, ICU length of stay and hospitalization time after
      surgery were also collected. RESULTS: After heparin neutralization, there were
      significantly elevated levels of fibrinogen in the FFP group, which were
      manifested by r-TEG parameters MAf and FLEV. No significant differences were
      observed between the two groups in postoperative bleeding, transfusion
      requirements and the usage of pharmacological agents. Recovery time was also
      comparable between the two groups. CONCLUSION: In conclusion, prophylactic use of
      FFP in the priming solution does not provide clinical benefits as presumed.
      Artificial colloids, such as Gelofusine, can be used safely and effectively as a
      substitute for FFP in the pump prime. TEG is an effective assessment tool to
      evaluate postoperative coagulation function in pediatric patients.

PMID- 24860125
TI  - Brain. Editorial.

PMID- 24860127
TI  - Retraction. Francis GJ, Martinez JA, Liu WQ, Xu K, Ayer A, Fine J, Tuor UI,
      Glazner G, Hanson LR, Frey WH 2nd, Toth C. Intranasal insulin prevents cognitive
      decline, cerebral atrophy and white matter changes in murine type I diabetic
      encephalopathy. Brain 2008 Dec;131(Pt 12):3311-34. doi:10.1093/brain/awn288.

PMID- 24860128
TI  - Invertebrate epigenomics: the brave new world of the spineless.

PMID- 24860130
TI  - The quest for the bionic arm.
AB  - The current state of research of upper extremity prosthetic devices is focused on
      creating a complete prosthesis with full motor and sensory function that will
      provide amputees with a near-normal human arm. Although advances are being made
      rapidly, many hurdles remain to be overcome before a functional, so-called bionic
      arm is a reality. Acquiring signals via nerve or muscle inputs will require
      either a reliable wireless device or direct wiring through an osseous-integrated
      implant. The best way to tap into the "knowledge" present in the peripheral nerve
      is yet to be determined. 

PMID- 24860129
TI  - Building a bigger box.

PMID- 24860126
TI  - The wide spectrum of tubulinopathies: what are the key features for the
      diagnosis?
AB  - Complex cortical malformations associated with mutations in tubulin genes:
      TUBA1A, TUBA8, TUBB2B, TUBB3, TUBB5 and TUBG1 commonly referred to as
      tubulinopathies, are a heterogeneous group of conditions with a wide spectrum of
      clinical severity. Among the 106 patients selected as having complex cortical
      malformations, 45 were found to carry mutations in TUBA1A (42.5%), 18 in TUBB2B
      (16.9%), 11 in TUBB3 (10.4%), three in TUBB5 (2.8%), and three in TUBG1 (2.8%).
      No mutations were identified in TUBA8. Systematic review of patients'
      neuroimaging and neuropathological data allowed us to distinguish at least five
      cortical malformation syndromes: (i) microlissencephaly (n = 12); (ii)
      lissencephaly (n = 19); (iii) central pachygyria and polymicrogyria-like cortical
      dysplasia (n = 24); (iv) generalized polymicrogyria-like cortical dysplasia (n =
      6); and (v) a 'simplified' gyral pattern with area of focal polymicrogyria (n =
      19). Dysmorphic basal ganglia are the hallmark of tubulinopathies (found in 75%
      of cases) and are present in 100% of central pachygyria and polymicrogyria-like
      cortical dysplasia and simplified gyral malformation syndromes. Tubulinopathies
      are also characterized by a high prevalence of corpus callosum agenesis (32/80;
      40%), and mild to severe cerebellar hypoplasia and dysplasia (63/80; 78.7%).
      Foetal cases (n = 25) represent the severe end of the spectrum and show specific
      abnormalities that provide insights into the underlying pathophysiology. The
      overall complexity of tubulinopathies reflects the pleiotropic effects of
      tubulins and their specific spatio-temporal profiles of expression. In line with
      previous reports, this large cohort further clarifies overlapping phenotypes
      between tubulinopathies and although current structural data do not allow
      prediction of mutation-related phenotypes, within each mutated gene there is an
      associated predominant pattern of cortical dysgenesis allowing some phenotype
      genotype correlation. The core phenotype of TUBA1A and TUBG1 tubulinopathies are
      lissencephalies and microlissencephalies, whereas TUBB2B tubulinopathies show in
      the majority, centrally predominant polymicrogyria-like cortical dysplasia. By
      contrast, TUBB3 and TUBB5 mutations cause milder malformations with focal or
      multifocal polymicrogyria-like cortical dysplasia with abnormal and simplified
      gyral pattern. 

PMID- 24860131
TI  - Vascular anomalies of the hand and wrist.
AB  - Vascular malformations of the hand and wrist are uncommon. They develop from
      aberrations in angiogenic signaling during vascular development. Unlike
      hemangiomas, which are characterized by biphasic growth and slow spontaneous
      involution, vascular malformations continue to grow proportionally with the
      child. Management is dictated by classification of the vascular malformations,
      which is based on flow characteristics (ie, low, high) and predominant cell type
      (ie, venous, lymphatic, capillary, combined, arteriovenous). Initial management
      is conservative, with the goal of providing relief from pain and swelling.
      Sclerotherapy, laser treatment, and arterial embolization may be beneficial in
      well-selected patients. Surgery is indicated in cases of persistent pain and
      uncontrolled limb swelling leading to functional impairment and/or neurologic
      compression. The goals of surgery are to excise as much of the lesion as possible
      while avoiding injury to adjacent nerves, minimizing blood loss, and preventing
      distal limb ischemia. This mandates careful preoperative planning and meticulous
      technique. Adjuvant treatments may be warranted, as in the case of preoperative
      embolization in patients with high-flow lesions. 

PMID- 24860132
TI  - Blood management strategies for total knee arthroplasty.
AB  - Perioperative blood loss during total knee arthroplasty can be significant, with
      magnitudes typically ranging from 300 mL to 1 L, with occasional reports of up to
      2 L. The resultant anemia can lead to severe complications, such as higher rates
      of postoperative infection, slower physical recovery, increased length of
      hospital stay, and increased morbidity and mortality. Although blood transfusions
      are now screened to a greater extent than in the past, they still carry the
      inherent risks of clerical error, infection, and immunologic reactions, all of
      which drive the need to develop alternative blood management strategies. Thorough
      patient evaluation is essential to individualize care through dedicated blood
      management and conservation pathways in order to maximize efficacy and avoid
      associated complications. Interventions may be implemented preoperatively,
      intraoperatively, and postoperatively. 

PMID- 24860134
TI  - Physeal arrest of the distal radius.
AB  - Fractures of the distal radius are among the most common pediatric fractures.
      Although most of these fractures heal without complication, some result in
      partial or complete physeal arrest. The risk of physeal arrest can be reduced by
      avoiding known risk factors during fracture management, including multiple
      attempts at fracture reduction. Athletes may place substantial compressive and
      shear forces across the distal radial physes, making them prone to growth arrest.
      Timely recognition of physeal arrest can allow for more predictable procedures to
      be performed, such as distal ulnar epiphysiodesis. In cases of partial arrest,
      physeal bar excision with interposition grafting can be performed. Once ulnar
      abutment is present, more invasive procedures may be required, including ulnar
      shortening osteotomy or radial lengthening. 

PMID- 24860133
TI  - Plantar and medial heel pain: diagnosis and management.
AB  - Heel pain is commonly encountered in orthopaedic practice. Establishing an
      accurate diagnosis is critical, but it can be challenging due to the complex
      regional anatomy. Subacute and chronic plantar and medial heel pain are most
      frequently the result of repetitive microtrauma or compression of neurologic
      structures, such as plantar fasciitis, heel pad atrophy, Baxter nerve entrapment,
      calcaneal stress fracture, and tarsal tunnel syndrome. Most causes of inferior
      heel pain can be successfully managed nonsurgically. Surgical intervention is
      reserved for patients who do not respond to nonsurgical measures. Although
      corticosteroid injections have a role in the management of select diagnoses, they
      should be used with caution. 

PMID- 24860135
TI  - Fungal osteomyelitis and septic arthritis.
AB  - Management of fungal osteomyelitis and fungal septic arthritis is challenging,
      especially in the setting of immunodeficiency and conditions that require
      immunosuppression. Because fungal osteomyelitis and fungal septic arthritis are
      rare conditions, study of their pathophysiology and treatment has been limited.
      In the literature, evidence-based treatment is lacking and, historically,
      outcomes have been poor. The most common offending organisms are Candida and
      Aspergillus, which are widely distributed in humans and soil. However, some
      fungal pathogens, such as Histoplasma, Blastomyces, Coccidioides, Cryptococcus,
      and Sporothrix, have more focal areas of endemicity. Fungal bone and joint
      infections result from direct inoculation, contiguous infection spread, or
      hematogenous seeding of organisms. These infections may be difficult to diagnose
      and eradicate, especially in the setting of total joint arthroplasty. Although
      there is no clear consensus on treatment, guidelines are available for management
      of many of these pathogens. 

PMID- 24860137
TI  - Iowa gambling task impairment in Parkinson's disease can be normalised by
      reduction of dopaminergic medication after subthalamic stimulation.
AB  - BACKGROUND: Impulse control disorders (ICD), including pathological gambling, are
      common in Parkinson's disease (PD) and tend to improve after subthalamic (STN)
      stimulation after a marked reduction of dopaminergic medication. In order to
      investigate the effect of STN stimulation on impulsive decision making, we used
      the Iowa Gambling task (IGT). METHODS: We investigated IGT performance in 20
      patients with PD before STN surgery with and without dopaminergic treatment and
      in 24 age-matched controls. All patients underwent an extensive
      neuropsychological interview screening for behavioural disorders. Assessment in
      patients was repeated 3 months after surgery without dopaminergic treatment with
      and without stimulation. RESULTS: Chronic antiparkinsonian treatment was
      drastically reduced after surgery (-74%). At baseline, on high chronic
      dopaminergic treatment 8/20 patients with PD presented with pathological
      hyperdopaminergic behaviours, which had resolved in 7/8 patients 3 months after
      surgery on low chronic dopaminergic treatment. Preoperative performance on the
      IGT was significantly impaired compared to after surgery. CONCLUSIONS:
      Dopaminergic medication likely contributes to the impairment in decision making
      underlying ICDs. Deep brain stimulation allows drastic reduction of dopaminergic
      medication and, thus, concomitant remediation of medication-induced impairment in
      decision making.

PMID- 24860138
TI  - Hyperoxia may be related to delayed cerebral ischemia and poor outcome after
      subarachnoid haemorrhage.
AB  - OBJECTIVE: To determine the association between exposure to hyperoxia and the
      risk of delayed cerebral ischaemia (DCI) after subarachnoid haemorrhage (SAH).
      METHODS: We analysed data from a single centre, prospective, observational cohort
      database. Patient inclusion criteria were age >=18 years, aneurysmal SAH,
      endotracheal intubation with mechanical ventilation, and arterial partial
      pressure of oxygen (PaO2) measurements. Hyperoxia was defined as the highest
      quartile of an area under the curve of PaO2, until the development of DCI
      (PaO2>=173 mm Hg). Poor outcome was defined as modified Rankin Scale 4-6 at 3
      months after SAH. RESULTS: Of 252 patients, there were no differences in baseline
      characteristics between the hyperoxia and control group. Ninety-seven (38.5%)
      patients developed DCI. The hyperoxia group had a higher incidence of DCI
      (p<0.001) and poor outcome (p=0.087). After adjusting for modified Fisher scale,
      rebleeding, global cerebral oedema, intracranial pressure crisis, pneumonia and
      sepsis, hyperoxia was independently associated with DCI (OR, 3.16; 95% CI 1.69 to
      5.92; p<0.001). After adjusting for age, Hunt-Hess grade, aneurysm size, Acute
      Physiology and Chronic Health Evaluation II score, rebleeding, pneumonia and
      sepsis, hyperoxia was independently associated with poor outcome (OR, 2.30; 95%
      CI 1.03 to 5.12; p=0.042). CONCLUSIONS: In SAH patients, exposure to hyperoxia
      was associated with DCI. Our findings suggest that exposure to excess oxygen
      after SAH may represent a modifiable factor for morbidity and mortality in this
      population.

PMID- 24860139
TI  - Delirium and dementia with Lewy bodies: distinct diagnoses or part of the same
      spectrum?
AB  - Dementia with Lewy bodies (DLB) is recognised as the second most common form of
      dementia in older people. Delirium is a condition of acute brain dysfunction for
      which a pre-existing diagnosis of dementia is a risk factor. Conversely delirium
      is associated with an increased risk of developing dementia. The reasons for this
      bidirectional relationship are not well understood. Our aim was to review
      possible similarities in the clinical presentation and pathophysiology between
      delirium and DLB, and explore possible links between these diagnoses. A
      systematic search using Medline, Embase and Psychinfo was performed. References
      were scanned for relevant articles, supplemented by articles identified from
      reference lists and those known to the authors. 94 articles were selected for
      inclusion in the review. Delirium and DLB share a number of clinical
      similarities, including global impairment of cognition, fluctuations in attention
      and perceptual abnormalities. Delirium is a frequent presenting feature of DLB.
      In terms of pathophysiological mechanisms, cholinergic dysfunction and genetics
      may provide a common link. Neuroimaging studies suggest a brain vulnerability in
      delirium which may also occur in dementia. The basal ganglia, which play a key
      role in DLB, have also been implicated in delirium. The role of Cerebrospinal
      fluid (CSF) and serum biomarkers for both diagnoses is an interesting area
      although some results are conflicting and further work in this area is needed.
      Delirium and DLB share a number of features and we hypothesise that delirium may,
      in some cases, represent early or 'prodromal' DLB. Further research is needed to
      test the novel hypothesis that delirium may be an early marker for future DLB,
      which would aid early diagnosis of DLB and identify those at high risk. 

PMID- 24860140
TI  - DARS2 gene clinical spectrum: new ideas regarding an underdiagnosed
      leukoencephalopathy.

PMID- 24860141
TI  - Reply: DARS2 gene clinical spectrum: new ideas regarding an underdiagnosed
      leukoencephalopathy.

PMID- 24860143
TI  - NF-kappaB controls axonal regeneration and degeneration through cell-specific
      balance of RelA and p50 in the adult CNS.
AB  - NF-kappaB is dually involved in neurogenesis and brain pathology. Here, we
      addressed its role in adult axoneogenesis by generating mutations of RelA (p65)
      and p50 (also known as NFKB1) heterodimers of canonical NF-kappaB. In addition to
      RelA activation in astrocytes, optic nerve axonotmesis caused a hitherto
      unrecognized induction of RelA in growth-inhibitory oligodendrocytes.
      Intraretinally, RelA was induced in severed retinal ganglion cells and was also
      expressed in bystander Muller glia. Cell-type-specific deletion of
      transactivating RelA in neurons and/or macroglia stimulated axonal regeneration
      in a distinct and synergistic pattern. By contrast, deletion of the p50
      suppressor subunit promoted spontaneous and post-injury Wallerian degeneration.
      Growth effects mediated by RelA deletion paralleled a downregulation of growth
      inhibitory Cdh1 (officially known as FZR1) and upregulation of the endogenous
      Cdh1 suppressor EMI1 (officially known as FBXO5). Pro-degenerative loss of p50,
      however, stabilized retinal Cdh1. In vitro, RelA deletion elicited opposing pro
      regenerative shifts in active nuclear and inactive cytoplasmic moieties of Cdh1
      and Id2. The involvement of NF-kappaB and cell-cycle regulators such as Cdh1 in
      regenerative processes of non-replicative neurons suggests novel mechanisms by
      which molecular reprogramming might be executed to stimulate adult axoneogenesis
      and treat central nervous system (CNS) axonopathies.

PMID- 24860142
TI  - Convergence of pathology in dementia with Lewy bodies and Alzheimer's disease: a
      role for the novel interaction of alpha-synuclein and presenilin 1 in disease.
AB  - A growing number of PSEN1 mutations have been associated with dementia with Lewy
      bodies and familial Alzheimer's disease with concomitant alpha-synuclein
      pathology. The objective of this study was to determine if PSEN1 plays a direct
      role in the development of alpha-synuclein pathology in these diseases. Using
      mass spectrometry, immunoelectron microscopy and fluorescence lifetime image
      microscopy based on Forster resonance energy transfer (FLIM-FRET) we identified
      alpha-synuclein as a novel interactor of PSEN1 in wild-type mouse brain tissue.
      The interaction of alpha-synuclein with PSEN1 was detected in post-mortem brain
      tissue from cognitively normal cases and was significantly increased in tissue
      from cases with dementia with Lewy bodies and familial Alzheimer's disease
      associated with known PSEN1 mutations. We confirmed an increased interaction of
      PSEN1 and alpha-synuclein in cell lines expressing well characterized familial
      Alzheimer's disease PSEN1 mutations, L166P and delta exon 9, and demonstrated
      that PSEN1 mutations associate with increased membrane association and
      accumulation of alpha-synuclein. Our data provides evidence of a molecular
      interaction of PSEN1 and alpha-synuclein that may explain the clinical and
      pathophysiological overlap seen in synucleinopathies, including Parkinson's
      disease, dementia with Lewy bodies, and some forms of Alzheimer's disease. 

PMID- 24860145
TI  - Why is personalized medicine relevant to public health?

PMID- 24860144
TI  - Metabolism and mis-metabolism of the neuropathological signature protein TDP-43.
AB  - TDP-43 (also known as TARDBP) is a pathological signature protein of
      neurodegenerative diseases, with TDP-43 proteinopathies including frontotemporal
      lobar degeneration (FTLD)-TDP and amyotrophic lateral sclerosis (ALS)-TDP. These
      TDP-43 proteinopathies are characterized by cytoplasmic insoluble TDP-43-positive
      aggregates in the diseased cells, the formation of which requires the seeding of
      TDP-25 fragment generated by caspase cleavage of TDP-43. We have investigated the
      metabolism and mis-metabolism of TDP-43 in cultured cells and found that
      endogenous and exogenously overexpressed TDP-43 is degraded not only by the
      ubiquitin proteasome system (UPS) and macroautophagy, but also by the chaperone
      mediated autophagy (CMA) mediated through an interaction between Hsc70 (also
      known as HSPA8) and ubiquitylated TDP-43. Furthermore, proteolytic cleavage of
      TDP-43 by caspase(s) is a necessary intermediate step for degradation of the
      majority of the TDP-43 protein, with the TDP-25 and TDP-35 fragments being the
      main substrates. Finally, we have determined the threshold level of the TDP-25
      fragment that is necessary for formation of the cytosolic TDP-43-positive
      aggregates in cells containing the full-length TDP-43 at an elevated level close
      to that found in patients with TDP-43 proteinopathies. A comprehensive model of
      the metabolism and mis-metabolism of TDP-43 in relation to these findings is
      presented.

PMID- 24860146
TI  - President's column.

PMID- 24860147
TI  - Effect of monomeric adiponectin on cardiac function and perfusion in anesthetized
      pig.
AB  - Adiponectin, the most abundant adipokine released by adipose tissue, appears to
      play an important role in the regulation of vascular endothelial and cardiac
      function. To date, however, the physiological effects of human monomeric
      adiponectin on the coronary vasculature and myocardial systo-diastolic function,
      as well as on parasympathetic/sympathetic involvement and nitric oxide (NO)
      release, have not yet been investigated. Thus, we planned to determine the
      primary in vivo effects of human monomeric adiponectin on coronary blood flow and
      cardiac contractility/relaxation and the related role of autonomic nervous
      system, adiponectin receptors, and NO. In 30 anesthetized pigs, human monomeric
      adiponectin was infused into the left anterior descending coronary artery at
      constant heart rate and arterial blood pressure, and the effects on coronary
      blood flow, left ventricular systo-diastolic function, myocardial oxygen
      metabolism, and NO release were examined. The mechanisms of the observed
      hemodynamic responses were also analyzed by repeating the highest dose of human
      monomeric adiponectin infusion after autonomic nervous system and NO blockade,
      and after specific adiponectin 1 receptor antagonist administration.
      Intracoronary human monomeric adiponectin caused dose-related increases of
      coronary blood flow and cardiac function. Those effects were accompanied by
      increased coronary NO release and coronary adiponectin levels. Moreover, the
      vascular effects of the peptide were prevented by blockade of beta2-adrenoceptors
      and NO synthase, whereas all effects of human monomeric adiponectin were
      prevented by adiponectin 1 receptor inhibitor. In conclusion, human monomeric
      adiponectin primarily increased coronary blood flow and cardiac systo-diastolic
      function through the involvement of specific receptors, beta2-adrenoceptors, and
      NO release. 

PMID- 24860148
TI  - PCSK6 regulated by LH inhibits the apoptosis of human granulosa cells via activin
      A and TGFbeta2.
AB  - Mammalian proprotein convertases (PCs) play an important role in
      folliculogenesis, as they proteolytically activate a variety of substrates such
      as the transforming growth factor beta (TGFbeta) superfamily. PC subtilism/kexin
      6 (PCSK6) is a member of the PC family and is ubiquitously expressed and
      implicated in many physiological and pathological processes. However, in human
      granulosa cells, the expression of the PC family members, their hormonal
      regulation, and the function of PCs are not clear. In this study, we found that
      PCSK6 is the most highly expressed PC family member in granulosa cells. LH
      increased PCSK6 mRNA level and PCSK6 played an anti-apoptosis function in KGN
      cells. Knockdown of PCSK6 not only increased the secretion of activin A and
      TGFbeta2 but also decreased the secretion of follistatin, estrogen, and the mRNA
      levels of FSH receptor (FSHR) and P450AROM (CYP19A1). We also found that, in the
      KGN human granulosa cell line, TGFbeta2 and activin A could promote the apoptosis
      of KGN cells and LH could regulate the follistatin level. These data indicate
      that PCSK6, which is regulated by LH, is highly expressed in human primary
      granulosa cells of pre-ovulatory follicles and plays important roles in
      regulating a series of downstream molecules and apoptosis of KGN cells. 

PMID- 24860149
TI  - VEGF-dependent and PDGF-dependent dynamic neurovascular reconstruction in the
      neurohypophysis of adult mice.
AB  - Hypothalamo-neurohypophysial system (HNS) releases arginine vasopressin (AVP) and
      oxytocin (OXT) from axonal terminals of the neurohypophysis (NH) into blood
      circulation for controlling body fluid homeostasis and lactation. Chronic osmotic
      and suckling stimulations have been shown to cause neurovascular and neuroglial
      reconstruction in the NH of adult mammals and no study has been reported for
      vascular dynamics. The aim of this study was to elucidate the occurrence of
      continuous angiogenesis and growth factor-dependent neurovascular reconstruction
      in the NH of adult mice. Active proliferation of endothelial cells and
      oligodendrocyte progenitor cells (OPCs) was observed using the
      immunohistochemistry of bromodeoxyuridine and Ki-67. Vascular endothelial growth
      factor A (VEGFA) and VEGF receptor 2 (VEGFR2 (KDR)) were highly expressed at
      pituicytes and endothelial cells respectively. Moreover, prominent expression of
      platelet-derived growth factor B (PDGFB) and PDGF receptor beta was observed at
      OXT-containing axonal terminals and pericytes respectively. Administration of the
      selective tyrosine kinase inhibitor AZD2171 for VEGFRs and STI571 for PDGFRs
      significantly decreased proliferation of endothelial cells and OPCs. Moreover,
      AZD2171 treatment decreased vascular density by facilitating apoptosis of
      endothelial cells and the withdrawal of its treatment led to remarkable rebound
      proliferation of endothelial cells, so that vascular density rapidly returned to
      normal levels. AZD2171 decreased the density of both AVP- and OXT-containing
      axonal terminals, whereas STI571 selectively decreased the density of AVP
      containing ones. Thus, this study demonstrates that the signaling pathways of
      VEGF and PDGF are crucial mediators for determining proliferation of endothelial
      cells and OPCs and the density of AVP- and OXT-containing axonal terminals in the
      HNS. 

PMID- 24860150
TI  - Effects of ubiquinol with fluid resuscitation following haemorrhagic shock on rat
      lungs, diaphragm, heart and kidneys.
AB  - Haemorrhagic shock (HS) and fluid resuscitation can lead to increased reactive
      oxygen species (ROS), contributing to ischaemia-reperfusion injury and organ
      damage. Ubiquinol is a potent antioxidant that decreases ROS. This study examined
      the effects of ubiquinol administered with fluid resuscitation following
      controlled HS. Adult male Sprague-Dawley rats were randomly assigned to treatment
      [ubiquinol, 1 mg (100 g body weight)(-1)] or control groups. Rats were subjected
      to 60 min of HS by removing 40% of the total blood volume to a mean arterial
      pressure ~45-55 mmHg. The animals were resuscitated with blood and lactated
      Ringer solution, with or without ubiquinol, and monitored for 120 min. At the end
      of the experiments, the rats were killed and the lungs, diaphragm, heart and
      kidneys harvested. Leucocytes were analysed for mitochondrial superoxide at
      baseline, end of shock and 120 min following fluid resuscitation using MitoSOX
      Red. Diaphragms were examined for hydrogen peroxide using dihydrofluorescein
      diacetate and confocal microscopy. The apoptosis in lungs, diaphragm, heart and
      kidneys was measured using fluorescence microscopy with acridine orange and
      ethidium bromide. Leucocyte mitochondrial superoxide levels were significantly
      lower in rats that received ubiquinol than in the control animals. Production of
      hydrogen peroxide and apoptosis were significantly reduced in the organs of rats
      treated with ubiquinol. These findings suggest that ubiquinol, administered with
      fluid resuscitation after HS, attenuates ROS production and apoptosis. Thus,
      ubiquinol is a potent antioxidant that may be used as a potential treatment to
      reduce organ injury following haemorrhagic events. 

PMID- 24860151
TI  - Trends in family planning and counselling for women with sickle cell disease in
      the UK over two decades.
AB  - BACKGROUND: Pregnancies in women with sickle cell disease (SCD) are known to have
      high rates of maternal and fetal mortality and morbidity. Given these pregnancy
      associated problems for women with SCD, advice both about pregnancy planning and
      about effective contraception are of paramount importance. This study sought to
      discover the contraception methods used by women with SCD, what complications
      women with SCD encounter with contraception, and their experiences of pre
      pregnancy counselling and pregnancy planning, and how such issues may have
      changed over the past two decades. METHOD: The study was a multicentre, interview
      based, cross-sectional study. Interviews were carried out with 102 women with
      SCD, in north and central London during 2010, concerning their current and
      previous contraceptive use, their pregnancy history, their menstrual history, and
      the advice they received concerning pregnancy planning and contraception. Patient
      information was anonymised and ethical approval was obtained. These data were
      compared with data from a similar study undertaken in 1993. RESULTS: There were
      significant differences in a number of key areas: the number of unplanned
      pregnancies decreased from 64% in 1993 to 53% in 2010. The number of women with
      SCD who were advised not to become pregnant also fell, from 36% to 15%. The use
      of combined oral contraceptive pills declined, from 45% of the women in 1993 to
      31% in 2010. Conversely the use of depot medroxyprogesterone acetate
      contraception (DMPA) and the levonorgestrel intrauterine system (LNG-IUS) both
      increased. CONCLUSIONS: Significant changes in the contraceptive methods used by
      women with SCD are demonstrated in the London population. LNG-IUS use in SCD has
      not been investigated before. There has been an encouraging decrease in the
      number of women with SCD who are advised not to become pregnant, perhaps
      reflecting an improvement in their overall health. Although the number of
      unplanned pregnancies has fallen, it remains high - emphasising the continuing
      need for women with SCD to have access to informed advice about pregnancy
      associated issues and contraception.

PMID- 24860152
TI  - Cochrane update: Predicting sustainability of intervention effects in public
      health evidence: identifying key elements to provide guidance.

PMID- 24860153
TI  - North and South: addressing the English health divide.

PMID- 24860154
TI  - Bedaquiline: a review of human pharmacokinetics and drug-drug interactions.
AB  - Bedaquiline has recently been approved for the treatment of pulmonary multidrug
      resistant tuberculosis (TB) as part of combination therapy in adults. It is
      metabolized primarily by the cytochrome P450 isoenzyme 3A4 (CYP3A4) to a less
      active N-monodesmethyl metabolite. Phase I and Phase II studies in healthy
      subjects and patients with drug-susceptible or multidrug-resistant TB have
      assessed the pharmacokinetics and drug-drug interaction profile of bedaquiline.
      Potential interactions have been assessed between bedaquiline and first- and
      second-line anti-TB drugs (rifampicin, rifapentine, isoniazid, pyrazinamide,
      ethambutol, kanamycin, ofloxacin and cycloserine), commonly used antiretroviral
      agents (lopinavir/ritonavir, nevirapine and efavirenz) and a potent CYP3A
      inhibitor (ketoconazole). This review summarizes the pharmacokinetic profile of
      bedaquiline as well as the results of the drug-drug interaction studies. 

PMID- 24860155
TI  - Comparative replication capacity of raltegravir-resistant strains and antiviral
      activity of the new-generation integrase inhibitor dolutegravir in human primary
      macrophages and lymphocytes.
AB  - OBJECTIVES: To evaluate the replication capacity and phenotypic susceptibility to
      dolutegravir and raltegravir of wild-type and raltegravir-resistant HIV-1 strains
      in several cellular systems. METHODS: The antiviral activities of dolutegravir
      and raltegravir were evaluated in human primary monocyte-derived macrophages
      (MDMs), peripheral blood mononuclear cells (PBMCs) and C8166 T lymphocytic cells.
      The following raltegravir resistance mutations were analysed: N155H, Y143C, N155H
      + Y143C and G140S+Q148H. RESULTS: In the absence of drug, the replication
      capacity of raltegravir-resistant viruses was strongly reduced compared with wild
      type in all cellular models analysed. In MDMs and PBMCs, a dramatic decrease in
      viral replication was observed for the double mutants N155H + Y143C and G140S +
      Q148H (ranging from 0.1% to 2.5% compared with wild-type). In MDMs, dolutegravir
      exhibited high potency, with EC50 and EC90 values of 1.1 +/- 0.9 and 5.5 +/- 3.4
      nM, respectively (comparable to raltegravir). These values (particularly for
      EC90) were significantly lower than those observed in PBMCs (EC50: 2.7 +/- 1.5
      nM; EC90: 14.8 +/- 0.9 nM) and C8166 cells (EC50: 5.5 +/- 0.8 nM; EC90: 64.8 +/-
      5.8 nM). In all cellular models analysed, dolutegravir showed full efficacy
      against N155H and Y143C mutants (dolutegravir fold-change resistance ranging from
      0.1 to 1.4; raltegravir fold-change resistance ranging from 0.1 to 10.3). In
      C8166 (the only cell model in which replication capacity was sufficient to
      perform the test) dolutegravir showed full efficacy against mutations N155H +
      Y143C (dolutegravir fold-change resistance: 0.6) and a slightly lower activity
      against G140S+Q148H (dolutegravir fold-change resistance: 2.1). CONCLUSIONS:
      Dolutegravir is effective in different HIV cellular targets and against
      raltegravir-resistant mutants. The high efficacy of dolutegravir in MDMs (cells
      with limited metabolism) has relevant clinical implications in light of the role
      of MDMs in the transmission of HIV infection and dissemination in different body
      compartments.

PMID- 24860156
TI  - Risk of new or recurrent cancer after a high perioperative inspiratory oxygen
      fraction during abdominal surgery.
AB  - BACKGROUND: Administration of supplemental oxygen in the perioperative period is
      controversial, as it may increase long-term mortality. Our aim was to assess the
      association between 80% oxygen and occurrence of subsequent cancer in patients
      undergoing abdominal surgery in a post hoc analysis of the PROXI trial. METHODS:
      The 1386 patients in the PROXI trial underwent elective or emergency laparotomy
      between 2006 and 2008 with randomization to either 80% or 30% oxygen during and
      for 2 h after surgery. We retrieved follow-up status regarding vital status, new
      cancer diagnoses, and new histological cancer specimens. Data were analysed using
      the Cox proportional hazards model. RESULTS: Follow-up was complete in 1377
      patients (99%) after a median of 3.9 yr. The primary outcome of new cancer
      diagnosis or new malignant histological specimen occurred in 140 of 678 patients
      (21%) in the 80% oxygen group vs 150 of 699 patients (21%) assigned to 30%
      oxygen; hazards ratio 1.06 [95% confidence interval (CI) 0.84, 1.34], P=0.62.
      Cancer-free survival was significantly shorter in the 80% oxygen group; hazards
      ratio 1.19 (95% CI 1.01, 1.42), P=0.04, as was the time between surgery and new
      cancer, median 335 vs. 434 days in the 30% oxygen group. In patients with
      localized disease, non-significant differences in cancer and cancer-free survival
      were found with hazard ratios of 1.31 and 1.29, respectively. CONCLUSIONS:
      Although new cancers occurred at similar rate, the cancer-free survival was
      significantly shorter in the 80% oxygen group, but this did not appear to explain
      the excess mortality in the 80% oxygen group. CLINICAL TRIAL REGISTRATION:
      ClinicalTrials.gov (NCT01723280).

PMID- 24860157
TI  - Effect of ventilation on cerebral oxygenation in patients undergoing surgery in
      the beach chair position: a randomized controlled trial.
AB  - BACKGROUND: Surgery in the beach chair position (BCP) may reduce cerebral blood
      flow and oxygenation, resulting in neurological injuries. The authors tested the
      hypothesis that a ventilation strategy designed to achieve end-tidal carbon
      dioxide (E'(CO2)) values of 40-42 mm Hg would increase cerebral oxygenation
      (Sct(O2)) during BCP shoulder surgery compared with a ventilation strategy
      designed to achieve E'(CO2) values of 30-32 mm Hg. METHODS: Seventy patients
      undergoing shoulder surgery in the BCP with general anaesthesia were enrolled in
      this randomized controlled trial. Mechanical ventilation was adjusted to maintain
      an E'(CO2) of 30-32 mm Hg in the control group and an E'(CO2) of 40-42 mm Hg in
      the study group. Cerebral oxygenation was monitored continuously in the operating
      theatre using near-infrared spectroscopy. Baseline haemodynamics and Sct(O2) were
      obtained before induction of anaesthesia, and these values were then measured and
      recorded continuously from induction of anaesthesia until tracheal extubation.
      The number of cerebral desaturation events (CDEs) (defined as a >=20% reduction
      in Sct(O2) from baseline values) was recorded. RESULTS: No significant
      differences between the groups were observed in haemodynamic variables or
      phenylephrine interventions during the surgical procedure. Sct(O2) values were
      significantly higher in the study 40-42 group throughout the intraoperative
      period (P<0.01). In addition, the incidence of CDEs was lower in the study 40-42
      group (8.8%) compared with the control 30-32 group (55.6%, P<0.0001).
      CONCLUSIONS: Cerebral oxygenation is significantly improved during BCP surgery
      when ventilation is adjusted to maintain E'(CO2) at 40-42 mm Hg compared with 30
      32 mm Hg. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT01546636.

PMID- 24860159
TI  - GenomeVISTA--an integrated software package for whole-genome alignment and
      visualization.
AB  - With the ubiquitous generation of complete genome assemblies for a variety of
      species, efficient tools for whole-genome alignment along with user-friendly
      visualization are critically important. Our VISTA family of tools for comparative
      genomics, based on algorithms for pairwise and multiple alignments of genomic
      sequences and whole-genome assemblies, has become one of the standard techniques
      for comparative analysis. Most of the VISTA programs have been implemented as Web
      accessible servers and are extensively used by the biomedical community. In this
      manuscript, we introduce GenomeVISTA: a novel implementation that incorporates
      most features of the VISTA family--fast and accurate alignment, visualization
      capabilities, GUI and analytical tools within a stand-alone software package.
      GenomeVISTA thus provides flexibility and security for users who need to conduct
      whole-genome comparisons on their own computers. AVAILABILITY AND IMPLEMENTATION:
      Implemented in Perl, C/C++ and Java, the source code is freely available for
      download at the VISTA Web site: http://genome.lbl.gov/vista/.

PMID- 24860158
TI  - Targeting mitochondrial metabolism by inhibiting autophagy in BRAF-driven
      cancers.
AB  - Metabolomic analyses of human tumors and mouse models of cancer have identified
      key roles for autophagy in supporting mitochondrial metabolism and homeostasis.
      In this review, we highlight data suggesting that autophagy inhibition may be
      particularly effective in BRAF-driven malignancies. Catalytic BRAF inhibitors
      have profound efficacy in tumors carrying activating mutations in Braf but are
      limited by the rapid emergence of resistance due in part to increased
      mitochondrial biogenesis and heightened rates of oxidative phosphorylation. We
      suggest that combined inhibition of autophagy and BRAF may overcome this
      limitation. SIGNIFICANCE: Braf(V600E)-driven tumors require autophagy and likely
      autophagy-provided substrates to maintain mitochondrial metabolism and to promote
      tumor growth, suggesting that autophagy ablation may improve cancer therapy.

PMID- 24860161
TI  - GT-Scan: identifying unique genomic targets.
AB  - A number of technologies, including CRISPR/Cas, transcription activator-like
      effector nucleases and zinc-finger nucleases, allow the user to target a chosen
      locus for genome editing or regulatory interference. Specificity, however, is a
      major problem, and the targeted locus must be chosen with care to avoid
      inadvertently affecting other loci ('off-targets') in the genome. To address this
      we have created 'Genome Target Scan' (GT-Scan), a flexible web-based tool that
      ranks all potential targets in a user-selected region of a genome in terms of how
      many off-targets they have. GT-Scan gives the user flexibility to define the
      desired characteristics of targets and off-targets via a simple 'target rule',
      and its interactive output allows detailed inspection of each of the most
      promising candidate targets. GT-Scan can be used to identify optimal targets for
      CRISPR/Cas systems, but its flexibility gives it potential to be adapted to other
      genome-targeting technologies as well. AVAILABILITY AND IMPLEMENTATION: GT-Scan
      can be run via the web at: http://gt-scan.braembl.org.au.

PMID- 24860160
TI  - Identification of chromosomal translocation hotspots via scan statistics.
AB  - MOTIVATION: The detection of genomic regions unusually rich in a given pattern is
      an important undertaking in the analysis of next-generation sequencing data.
      Recent studies of chromosomal translocations in activated B lymphocytes have
      identified regions that are frequently translocated to c-myc oncogene. A
      quantitative method for the identification of translocation hotspots was crucial
      to this study. Here we improve this analysis by using a simple probabilistic
      model and the framework provided by scan statistics to define the number and
      location of translocation breakpoint hotspots. A key feature of our method is
      that it provides a global chromosome-wide nominal control level to clustering, as
      opposed to previous methods based on local criteria. While being motivated by a
      specific application, the detection of unusual clusters is a widespread problem
      in bioinformatics. We expect our method to be useful in the analysis of data from
      other experimental approaches such as of ChIP-seq and 4C-seq. RESULTS: The
      analysis of translocations from B lymphocytes with the method described here
      reveals the presence of longer hotspots when compared with those defined
      previously. Further, we show that the hotspot size changes substantially in the
      absence of DNA repair protein 53BP1. When 53BP1 deficiency is combined with
      overexpression of activation-induced cytidine deaminase, the hotspot length
      increases even further. These changes are not detected by previous methods that
      use local significance criteria for clustering. Our method is also able to
      identify several exclusive translocation hotspots located in genes of known tumor
      supressors. AVAILABILITY AND IMPLEMENTATION: The detection of translocation
      hotspots is done with hot_scan, a program implemented in R and Perl. Source code
      and documentation are freely available for download at
      https://github.com/itojal/hot_scan.

PMID- 24860163
TI  - A forward genetic screen reveals essential and non-essential RNAi factors in
      Paramecium tetraurelia.
AB  - In most eukaryotes, small RNA-mediated gene silencing pathways form complex
      interacting networks. In the ciliate Paramecium tetraurelia, at least two RNA
      interference (RNAi) mechanisms coexist, involving distinct but overlapping sets
      of protein factors and producing different types of short interfering RNAs
      (siRNAs). One is specifically triggered by high-copy transgenes, and the other by
      feeding cells with double-stranded RNA (dsRNA)-producing bacteria. In this study,
      we designed a forward genetic screen for mutants deficient in dsRNA-induced
      silencing, and a powerful method to identify the relevant mutations by whole
      genome sequencing. We present a set of 47 mutant alleles for five genes,
      revealing two previously unknown RNAi factors: a novel Paramecium-specific
      protein (Pds1) and a Cid1-like nucleotidyl transferase. Analyses of allelic
      diversity distinguish non-essential and essential genes and suggest that the
      screen is saturated for non-essential, single-copy genes. We show that non
      essential genes are specifically involved in dsRNA-induced RNAi while essential
      ones are also involved in transgene-induced RNAi. One of the latter, the RNA
      dependent RNA polymerase RDR2, is further shown to be required for all known
      types of siRNAs, as well as for sexual reproduction. These results open the way
      for the dissection of the genetic complexity, interconnection, mechanisms and
      natural functions of RNAi pathways in P. tetraurelia. 

PMID- 24860162
TI  - Mechanisms promoting escape from mitotic stress-induced tumor cell death.
AB  - Non-small cell lung cancer (NSCLC) is notorious for its paltry responses to first
      line therapeutic regimens. In contrast to acquired chemoresistance, little is
      known about the molecular underpinnings of the intrinsic resistance of chemo
      naive NSCLC. Here we report that intrinsic resistance to paclitaxel in NSCLC
      occurs at a cell-autonomous level because of the uncoupling of mitotic defects
      from apoptosis. To identify components that permit escape from mitotic stress
      induced death, we used a genome-wide RNAi-based strategy, which combines a high
      throughput toxicity screen with a live-cell imaging platform to measure mitotic
      fate. This strategy revealed that prolonging mitotic arrest with a small molecule
      inhibitor of the APC/cyclosome could sensitize otherwise paclitaxel-resistant
      NSCLC. We also defined novel roles for CASC1 and TRIM69 in supporting resistance
      to spindle poisons. CASC1, which is frequently co-amplified with KRAS in lung
      tumors, is essential for microtubule polymerization and satisfaction of the
      spindle assembly checkpoint. TRIM69, which associates with spindle poles and
      promotes centrosomal clustering, is essential for formation of a bipolar spindle.
      Notably, RNAi-mediated attenuation of CASC1 or TRIM69 was sufficient to inhibit
      tumor growth in vivo. On the basis of our results, we hypothesize that tumor
      evolution selects for a permissive mitotic checkpoint, which may promote survival
      despite chromosome segregation errors. Attacking this adaptation may restore the
      apoptotic consequences of mitotic damage to permit the therapeutic eradication of
      drug-resistant cancer cells.

PMID- 24860165
TI  - Motif enrichment tool.
AB  - The Motif Enrichment Tool (MET) provides an online interface that enables users
      to find major transcriptional regulators of their gene sets of interest. MET
      searches the appropriate regulatory region around each gene and identifies which
      transcription factor DNA-binding specificities (motifs) are statistically
      overrepresented. Motif enrichment analysis is currently available for many
      metazoan species including human, mouse, fruit fly, planaria and flowering
      plants. MET also leverages high-throughput experimental data such as ChIP-seq and
      DNase-seq from ENCODE and ModENCODE to identify the regulatory targets of a
      transcription factor with greater precision. The results from MET are produced in
      real time and are linked to a genome browser for easy follow-up analysis. Use of
      the web tool is free and open to all, and there is no login requirement. ADDRESS:
      http://veda.cs.uiuc.edu/MET/.

PMID- 24860164
TI  - Structure and semi-sequence-specific RNA binding of Nrd1.
AB  - In Saccharomyces cerevisiae, the Nrd1-dependent termination and processing
      pathways play an important role in surveillance and processing of non-coding
      ribonucleic acids (RNAs). The termination and subsequent processing is dependent
      on the Nrd1 complex consisting of two RNA-binding proteins Nrd1 and Nab3 and Sen1
      helicase. It is established that Nrd1 and Nab3 cooperatively recognize specific
      termination elements within nascent RNA, GUA[A/G] and UCUU[G], respectively.
      Interestingly, some transcripts do not require GUA[A/G] motif for transcription
      termination in vivo and binding in vitro, suggesting the existence of alternative
      Nrd1-binding motifs. Here we studied the structure and RNA-binding properties of
      Nrd1 using nuclear magnetic resonance (NMR), fluorescence anisotropy and
      phenotypic analyses in vivo. We determined the solution structure of a two-domain
      RNA-binding fragment of Nrd1, formed by an RNA-recognition motif and helix-loop
      bundle. NMR and fluorescence data show that not only GUA[A/G] but also several
      other G-rich and AU-rich motifs are able to bind Nrd1 with affinity in a low
      micromolar range. The broad substrate specificity is achieved by adaptable
      interaction surfaces of the RNA-recognition motif and helix-loop bundle domains
      that sandwich the RNA substrates. Our findings have implication for the role of
      Nrd1 in termination and processing of many non-coding RNAs arising from
      bidirectional pervasive transcription. 

PMID- 24860166
TI  - Brd4 activates P-TEFb for RNA polymerase II CTD phosphorylation.
AB  - The bromodomain protein Brd4 regulates the transcription of signal-inducible
      genes. This is achieved by recruiting the positive transcription elongation
      factor P-TEFb to promoters by its P-TEFb interaction domain (PID). Here we show
      that Brd4 stimulates the kinase activity of P-TEFb for phosphorylation of the C
      terminal domain (CTD) of RNA polymerase II over basal levels. The CTD
      phosphorylation saturation levels, the preferences for pre-phosphorylated
      substrates, and the phosphorylation specificity for Ser5 of the CTD however
      remain unchanged. Inhibition of P-TEFb by Hexim1 is relieved by Brd4, although no
      mutual displacement with the Cyclin T-binding domain of Hexim1 was observed. Brd4
      PID shows a surprising sequence motif similarity to the trans-activating Tat
      protein from HIV-1, which includes a core RxL motif, a polybasic cluster known as
      arginine-rich motif, and a C-terminal leucine motif. Mutation of these motifs to
      alanine significantly diminished the stimulatory effect of Brd4 and fully
      abrogated its activation potential in presence of Hexim1. Yet the protein was not
      found to bind Cyclin T1 as Tat, but only P-TEFb with a dissociation constant of
      0.5 MUM. Our data suggest a model where Brd4 acts on the kinase subunit of P-TEFb
      to relieve inhibition and stimulate substrate recognition. 

PMID- 24860167
TI  - Divergent LIN28-mRNA associations result in translational suppression upon the
      initiation of differentiation.
AB  - LIN28 function is fundamental to the activity and behavior of human embryonic
      stem cells (hESCs) and induced pluripotent stem cells. Its main roles in these
      cell types are the regulation of translational efficiency and let-7 miRNA
      maturation. However, LIN28-associated mRNA cargo shifting and resultant
      regulation of translational efficiency upon the initiation of differentiation
      remain unknown. An RNA-immunoprecipitation and microarray analysis protocol,
      eRIP, that has high specificity and sensitivity was developed to test endogenous
      LIN28-associated mRNA cargo shifting. A combined eRIP and polysome analysis of
      early stage differentiation of hESCs with two distinct differentiation cues
      revealed close similarities between the dynamics of LIN28 association and
      translational modulation of genes involved in the Wnt signaling, cell cycle, RNA
      metabolism and proteasomal pathways. Our data demonstrate that change in
      translational efficiency is a major contributor to early stages of
      differentiation of hESCs, in which LIN28 plays a central role. This implies that
      eRIP analysis of LIN28-associated RNA cargoes may be used for rapid functional
      quality control of pluripotent stem cells under manufacture for therapeutic
      applications. 

PMID- 24860169
TI  - SSpro/ACCpro 5: almost perfect prediction of protein secondary structure and
      relative solvent accessibility using profiles, machine learning and structural
      similarity.
AB  - MOTIVATION: Accurately predicting protein secondary structure and relative
      solvent accessibility is important for the study of protein evolution, structure
      and function and as a component of protein 3D structure prediction pipelines.
      Most predictors use a combination of machine learning and profiles, and thus must
      be retrained and assessed periodically as the number of available protein
      sequences and structures continues to grow. RESULTS: We present newly trained
      modular versions of the SSpro and ACCpro predictors of secondary structure and
      relative solvent accessibility together with their multi-class variants SSpro8
      and ACCpro20. We introduce a sharp distinction between the use of sequence
      similarity alone, typically in the form of sequence profiles at the input level,
      and the additional use of sequence-based structural similarity, which uses
      similarity to sequences in the Protein Data Bank to infer annotations at the
      output level, and study their relative contributions to modern predictors. Using
      sequence similarity alone, SSpro's accuracy is between 79 and 80% (79% for
      ACCpro) and no other predictor seems to exceed 82%. However, when sequence-based
      structural similarity is added, the accuracy of SSpro rises to 92.9% (90% for
      ACCpro). Thus, by combining both approaches, these problems appear now to be
      essentially solved, as an accuracy of 100% cannot be expected for several well
      known reasons. These results point also to several open technical challenges,
      including (i) achieving on the order of >= 80% accuracy, without using any
      similarity with known proteins and (ii) achieving on the order of >= 85%
      accuracy, using sequence similarity alone. AVAILABILITY AND IMPLEMENTATION:
      SSpro, SSpro8, ACCpro and ACCpro20 programs, data and web servers are available
      through the SCRATCH suite of protein structure predictors at
      http://scratch.proteomics.ics.uci.edu.

PMID- 24860168
TI  - Disease-associated CAG.CTG triplet repeats expand rapidly in non-dividing mouse
      cells, but cell cycle arrest is insufficient to drive expansion.
AB  - Genetically unstable expanded CAG.CTG trinucleotide repeats are causal in a
      number of human disorders, including Huntington disease and myotonic dystrophy
      type 1. It is still widely assumed that DNA polymerase slippage during
      replication plays an important role in the accumulation of expansions.
      Nevertheless, somatic mosaicism correlates poorly with the proliferative capacity
      of the tissue and rates of cell turnover, suggesting that expansions can occur in
      the absence of replication. We monitored CAG.CTG repeat instability in transgenic
      mouse cells arrested by chemical or genetic manipulation of the cell cycle and
      generated unequivocal evidence for the continuous accumulation of repeat
      expansions in non-dividing cells. Importantly, the rates of expansion in non
      dividing cells were at least as high as those of proliferating cells. These data
      are consistent with a major role for cell division-independent expansion in
      generating somatic mosaicism in vivo. Although expansions can accrue in non
      dividing cells, we also show that cell cycle arrest is not sufficient to drive
      instability, implicating other factors as the key regulators of tissue-specific
      instability. Our data reveal that de novo expansion events are not limited to S
      phase and further support a cell division-independent mutational pathway. 

PMID- 24860170
TI  - Nicotinic ACh receptors in the hippocampal circuit; functional expression and
      role in synaptic plasticity.
AB  - Acetylcholine (ACh) can regulate neuronal excitability in the hippocampus, an
      important area in the brain for learning and memory, by acting on both nicotinic
      (nAChRs) and muscarinic ACh receptors. The primary cholinergic input to the
      hippocampus arises from the medial septum and diagonal band of Broca (MS-DBB),
      and we investigated how their activation regulated hippocampal synaptic
      plasticity. We found that activation of these endogenous cholinergic inputs can
      directly induce different forms of hippocampal synaptic plasticity with a timing
      precision in the millisecond range. Furthermore, we observed a prolonged
      enhancement of excitability both pre- and postsynaptically. Lastly we found that
      the presence of the alpha7 nAChR subtype to both pre- and postsynaptic sites
      appeared to be required to induce this plasticity. We propose that alpha7 nAChRs
      coordinate pre- and postsynaptic activities to induce glutamatergic synaptic
      plasticity, and thus provide a novel mechanism underlying physiological neuronal
      communication that could lead to timing-dependent synaptic plasticity in the
      hippocampus.

PMID- 24860172
TI  - The effective neural drive to muscles is the common synaptic input to motor
      neurons.

PMID- 24860171
TI  - Myoblasts from intrauterine growth-restricted sheep fetuses exhibit intrinsic
      deficiencies in proliferation that contribute to smaller semitendinosus
      myofibres.
AB  - Intrauterine growth restriction (IUGR) reduces skeletal muscle mass in fetuses
      and offspring. Our objective was to determine whether myoblast dysfunction due to
      intrinsic cellular deficiencies or serum factors reduces myofibre hypertrophy in
      IUGR fetal sheep. At 134 days, IUGR fetuses weighed 67% less (P < 0.05) than
      controls and had smaller (P < 0.05) carcasses and semitendinosus myofibre areas.
      IUGR semitendinosus muscles had similar percentages of pax7-positive nuclei and
      pax7 mRNA but lower (P < 0.05) percentages of myogenin-positive nuclei (7 +/- 2%
      and 13 +/- 2%), less myoD and myogenin mRNA, and fewer (P < 0.05) proliferating
      myoblasts (PNCA-positive-pax7-positive) than controls (44 +/- 2% vs. 52 +/- 1%).
      Primary myoblasts were isolated from hindlimb muscles, and after 3 days in growth
      media (20% fetal bovine serum, FBS), myoblasts from IUGR fetuses had 34% fewer (P
      < 0.05) myoD-positive cells than controls and replicated 20% less (P < 0.05)
      during a 2 h BrdU pulse. IUGR myoblasts also replicated less (P < 0.05) than
      controls during a BrdU pulse after 3 days in media containing 10% control or IUGR
      fetal sheep serum (FSS). Both myoblast types replicated less (P < 0.05) with IUGR
      FSS-supplemented media compared to control FSS-supplemented media. In
      differentiation-promoting media (2% FBS), IUGR and control myoblasts had similar
      percentages of myogenin-positive nuclei after 5 days and formed similar-sized
      myotubes after 7 days. We conclude that intrinsic cellular deficiencies in IUGR
      myoblasts and factors in IUGR serum diminish myoblast proliferation and myofibre
      size in IUGR fetuses, but intrinsic myoblast deficiencies do not affect
      differentiation. Furthermore, the persistent reduction in IUGR myoblast
      replication shows adaptive deficiencies that explain poor muscle growth in IUGR
      newborn offspring.

PMID- 24860173
TI  - Exercise training modulates functional sympatholysis and alpha-adrenergic
      vasoconstrictor responsiveness in hypertensive and normotensive individuals.
AB  - Essential hypertension is linked to an increased sympathetic vasoconstrictor
      activity and reduced tissue perfusion. We investigated the role of exercise
      training on functional sympatholysis and postjunctional alpha-adrenergic
      responsiveness in individuals with essential hypertension. Leg haemodynamics were
      measured before and after 8 weeks of aerobic training (3-4 times per week) in
      eight hypertensive (47 +/- 2 years) and eight normotensive untrained individuals
      (46 +/- 1 years) during arterial tyramine infusion, arterial ATP infusion and/or
      one-legged knee extensions. Before training, exercise hyperaemia and leg vascular
      conductance (LVC) were lower in the hypertensive individuals (P < 0.05) and
      tyramine lowered exercise hyperaemia and LVC in both groups (P < 0.05). Training
      lowered blood pressure in the hypertensive individuals (P < 0.05) and exercise
      hyperaemia was similar to the normotensive individuals in the trained state.
      After training, tyramine did not reduce exercise hyperaemia or LVC in either
      group. When tyramine was infused at rest, the reduction in blood flow and LVC was
      similar between groups, but exercise training lowered the magnitude of the
      reduction in blood flow and LVC (P < 0.05). There was no difference in the
      vasodilatory response to infused ATP or in muscle P2Y2 receptor content between
      the groups before and after training. However, training lowered the vasodilatory
      response to ATP and increased skeletal muscle P2Y2 receptor content in both
      groups (P < 0.05). These results demonstrate that exercise training improves
      functional sympatholysis and reduces postjunctional alpha-adrenergic
      responsiveness in both normo- and hypertensive individuals. The ability for
      functional sympatholysis and the vasodilator and sympatholytic effect of
      intravascular ATP appear not to be altered in essential hypertension.

PMID- 24860174
TI  - Muscle-specific kinase (MuSK) autoantibodies suppress the MuSK pathway and ACh
      receptor retention at the mouse neuromuscular junction.
AB  - Muscle-specific kinase (MuSK) autoantibodies from myasthenia gravis patients can
      block the activation of MuSK in vitro and/or reduce the postsynaptic localization
      of MuSK. Here we use a mouse model to examine the effects of MuSK autoantibodies
      upon some key components of the postsynaptic MuSK pathway and upon the regulation
      of junctional ACh receptor (AChR) numbers. Mice became weak after 14 daily
      injections of anti-MuSK-positive patient IgG. The intensity and area of AChR
      staining at the motor endplate was markedly reduced. Pulse-labelling of AChRs
      revealed an accelerated loss of pre-existing AChRs from postsynaptic AChR
      clusters without a compensatory increase in incorporation of (newly synthesized)
      replacement AChRs. Large, postsynaptic AChR clusters were replaced by a
      constellation of tiny AChR microaggregates. Puncta of AChR staining also appeared
      in the cytoplasm beneath the endplate. Endplate staining for MuSK, activated Src,
      rapsyn and AChR were all reduced in intensity. In the tibialis anterior muscle
      there was also evidence that phosphorylation of the AChR beta-subunit-Y390 was
      reduced at endplates. In contrast, endplate staining for beta-dystroglycan
      (through which rapsyn couples AChR to the synaptic basement membrane) remained
      intense. The results suggest that anti-MuSK IgG suppresses the endplate density
      of MuSK, thereby down-regulating MuSK signalling activity and the retention of
      junctional AChRs locally within the postsynaptic membrane scaffold. 

PMID- 24860175
TI  - Native store-operated calcium channels are functionally expressed in mouse spinal
      cord dorsal horn neurons and regulate resting calcium homeostasis.
AB  - Store-operated calcium channels (SOCs) are calcium-selective cation channels that
      mediate calcium entry in many different cell types. Store-operated calcium entry
      (SOCE) is involved in various cellular functions. Increasing evidence suggests
      that impairment of SOCE is responsible for numerous disorders. A previous study
      demonstrated that YM-58483, a potent SOC inhibitor, strongly attenuates chronic
      pain by systemic or intrathecal injection and completely blocks the second phase
      of formalin-induced spontaneous nocifensive behaviour, suggesting a potential
      role of SOCs in central sensitization. However, the expression of SOCs, their
      molecular identity and function in spinal cord dorsal horn neurons remain
      elusive. Here, we demonstrate that SOCs are expressed in dorsal horn neurons.
      Depletion of calcium stores from the endoplasmic reticulum (ER) induced large
      sustained calcium entry, which was blocked by SOC inhibitors, but not by voltage
      gated calcium channel blockers. Depletion of ER calcium stores activated inward
      calcium-selective currents, which was reduced by replacing Ca(2+) with Ba(2+) and
      reversed by SOC inhibitors. Using the small inhibitory RNA knockdown approach, we
      identified both STIM1 and STIM2 as important mediators of SOCE and SOC current,
      and Orai1 as a key component of the Ca(2+) release-activated Ca(2+) channels in
      dorsal horn neurons. Knockdown of STIM1, STIM2 or Orai1 decreased resting Ca(2+)
      levels. We also found that activation of neurokinin 1 receptors led to SOCE and
      activation of SOCs produced an excitatory action in dorsal horn neurons. Our
      findings reveal that a novel SOC signal is present in dorsal horn neurons and may
      play an important role in pain transmission. 

PMID- 24860176
TI  - Noradrenergic modulation of masseter muscle activity during natural rapid eye
      movement sleep requires glutamatergic signalling at the trigeminal motor nucleus.
AB  - Noradrenergic neurotransmission in the brainstem is closely coupled to changes in
      muscle activity across the sleep-wake cycle, and noradrenaline is considered to
      be a key excitatory neuromodulator that reinforces the arousal-related stimulus
      on motoneurons to drive movement. However, it is unknown if alpha-1
      noradrenoceptor activation increases motoneuron responsiveness to excitatory
      glutamate (AMPA) receptor-mediated inputs during natural behaviour. We studied
      the effects of noradrenaline on AMPA receptor-mediated motor activity at the
      motoneuron level in freely behaving rats, particularly during rapid eye movement
      (REM) sleep, a period during which both AMPA receptor-triggered muscle twitches
      and periods of muscle quiescence in which AMPA drive is silent are exhibited.
      Male rats were subjected to electromyography and electroencephalography recording
      to monitor sleep and waking behaviour. The implantation of a cannula into the
      trigeminal motor nucleus of the brainstem allowed us to perfuse noradrenergic and
      glutamatergic drugs by reverse microdialysis, and thus to use masseter muscle
      activity as an index of motoneuronal output. We found that endogenous excitation
      of both alpha-1 noradrenoceptor and AMPA receptors during waking are coupled to
      motor activity; however, REM sleep exhibits an absence of endogenous alpha-1
      noradrenoceptor activity. Importantly, exogenous alpha-1 noradrenoceptor
      stimulation cannot reverse the muscle twitch suppression induced by AMPA receptor
      blockade and nor can it elevate muscle activity during quiet REM, a phase when
      endogenous AMPA receptor activity is subthreshold. We conclude that the presence
      of an endogenous glutamatergic drive is necessary for noradrenaline to trigger
      muscle activity at the level of the motoneuron in an animal behaving naturally. 

PMID- 24860177
TI  - Integrated analysis identifies different metabolic signatures for tumor
      initiating cells in a murine glioblastoma model.
AB  - BACKGROUND: The metabolic preference of malignant glioma for glycolysis as an
      energy source is a potential therapeutic target. As a result of the cellular
      heterogeneity of these tumors, however, the relation between glycolytic
      preference, tumor formation, and tumor cell clonogenicity has remained unknown.
      To address this issue, we analyzed the metabolic profiles of isogenic glioma
      initiating cells (GICs) in a mouse model. METHODS: GICs were established by
      overexpression of H-Ras(V12) in Ink4a/Arf-null neural stem cells. Subpopulations
      of these cells were obtained by single-cell cloning, and clones differing in
      extracellular acidification potential were assessed for metabolic
      characteristics. Tumors formed after intracranial implantation of these clones in
      mice were examined for pathological features of glioma and expression of
      glycolytic enzymes. RESULTS: Malignant transformation of neural stem cells
      resulted in a shift in metabolism characterized by an increase in lactic acid
      production. However, isogenic clonal populations of GICs manifested pronounced
      differences in glucose and oxygen consumption, lactate production, and nucleoside
      levels. These differences were paralleled by differential expression of
      glycolytic enzymes such as hexokinase 2 and pyruvate kinase M2, with this
      differential expression also being evident in tumors formed by these clones in
      vivo. CONCLUSIONS: The metabolic characteristics of glioma cells appear early
      during malignant transformation and persist until the late stages of tumor
      formation. Even isogenic clones may be heterogeneous in terms of metabolic
      features, however, suggesting that a more detailed understanding of the metabolic
      profile of glioma is imperative for effective therapeutic targeting.

PMID- 24860178
TI  - Predicting the likelihood of an isocitrate dehydrogenase 1 or 2 mutation in
      diagnoses of infiltrative glioma.
AB  - BACKGROUND: Several variables are associated with the likelihood of isocitrate
      dehydrogenase 1 or 2 (IDH1/2) mutation in gliomas, though no guidelines yet exist
      for when testing is warranted, especially when an R132H IDH1 immunostain is
      negative. METHODS: A cohort of 89 patients was used to build IDH1/2 mutation
      prediction models in World Health Organization grades II-IV gliomas, and an
      external cohort of 100 patients was used for validation. Logistic regression and
      backward model selection with the Akaike information criterion were used to
      develop prediction models. RESULTS: A multivariable model, incorporating patient
      age, glioblastoma multiforme diagnosis, and prior history of grade II or III
      glioma, was developed to predict IDH1/2 mutation probability. This model
      generated an area under the curve (AUC) of 0.934 (95% CI: 0.878, 0.978) in the
      external validation cohort and 0.941 (95% CI: 0.918, 0.962) in the cohort of The
      Cancer Genome Atlas. When R132H IDH1 immunostain information was added, AUC
      increased to 0.986 (95% CI: 0.967, 0.998). This model had an AUC of 0.947 (95%
      CI: 0.891, 0.995) in predicting whether an R132H IDH1 immunonegative case
      harbored a less common IDH1 or IDH2 mutation. The models were also 94% accurate
      in predicting IDH1/2 mutation status in gliomas from The Cancer Genome Atlas. An
      interactive web-based application for calculating the probability of an IDH1/2
      mutation is now available using these models. CONCLUSIONS: We have integrated
      multiple variables to generate a probability of an IDH1/2 mutation. The
      associated web-based application can help triage diffuse gliomas that would
      benefit from mutation testing in both clinical and research settings.

PMID- 24860179
TI  - Ablation of epicardial ganglionated plexi increases atrial vulnerability to
      arrhythmias in dogs.
AB  - BACKGROUND: Previous studies have suggested that systematic ablation of
      ganglionated plexi (GP) could increase the short-term success rate of
      radiofrequency ablation for atrial fibrillation, but the long-term efficacy of
      this approach is not fully established. METHODS AND RESULTS: Twenty-four mongrel
      dogs were divided into 3 groups: epicardial GP ablation group 1 (n=8), epicardial
      GP ablation group 2 (n=8), and a sham operation group (n=8). In the 2 epicardial
      GP ablation groups, the 4 major GP and the ligament of Marshall were
      systematically ablated. The effective refractory period and inducibility of
      tachyarrhythmias were measured before and immediately after GP ablation in
      epicardial GP ablation group 1 and 8 weeks later in the other 2 groups. Tyrosine
      hydroxylase and choline acetyltransferase expressions were also determined
      immunohistochemically 8 weeks later in the latter groups. Compared with
      epicardial GP ablation group 1 and the sham operation group, epicardial GP
      ablation group 2 had the shortest atrial and ventricular effective refractory
      period and the highest inducibility of atrial tachyarrhythmias. The inducibility
      of ventricular tachyarrhythmias among the 3 groups was comparable. The density of
      tyrosine hydroxylase- and choline acetyltransferase-positive nerves in the atrium
      was the highest in epicardial GP group 2, whereas there were no significant
      intergroup differences in the densities of these 2 types of nerves in the
      ventricle. CONCLUSIONS: After 8 weeks of healing, epicardial GP ablation without
      additional atrial ablation was potentially proarrhythmic, which may be
      attributable to decreased atrial effective refractory period and hyper
      reinnervation involving both sympathetic and parasympathetic nerves.

PMID- 24860181
TI  - Endometrial biopsy in women with abnormal uterine bleeding: inadequate and
      unassessable categorisation is not clinically relevant.
AB  - AIMS: Inadequate endometrial biopsy comprises a dilemma for gynaecologists and
      histopathologists alike. This study was conducted to assess the clinical merit of
      classifying scant endometrial biopsy into inadequate and unassessable using
      McCluggage criteria. METHODS: We retrospectively classified 268 endometrial
      biopsies, initially reported as inadequate, into inadequate (n=74) and
      unassessable (n=174) using McCluggage criteria after excluding 20 cases; all
      taken from patients aged >=50 years with abnormal uterine bleeding attending
      Sandwell and West Birmingham Hospitals, UK from 1 January 2007 until 30 September
      2012. The electronic clinical records were reviewed to find out the consequent
      clinical decisions and final outcomes. The follow-up period was 15 months after
      including the last patient. RESULTS: The median age was 57 years (range: 50-97),
      and the median number of visits to hospital till the diagnosis was achieved was 2
      (range: 1-4). The final diagnosis of endometrial hyperplasia or cancer was
      reported in 9 cases; 5 (7.1%) with an initial finding of inadequate and 4 with
      unassessable (2.4%); the difference was statistically insignificant (p=0.13).
      More patients in the inadequate category (82.4%) underwent further investigations
      when compared with the unassessable category (68.4%); the difference was
      statistically significant (p=0.029). There was no statistically significant
      difference in the inadequate to unassessable ratio when the endometrial thickness
      was >=5 mm or <5 mm within the Pipelle group (p=0.46) or the curettage group
      (p=0.34). CONCLUSIONS: Our findings suggest that categorising scant endometrial
      specimens into inadequate or unassessable has no clinical implications. The
      gynaecologist should interpret the histopathology report in the light of clinical
      scenario.

PMID- 24860182
TI  - The changing health status of economic migrants to the European Union in the
      aftermath of the economic crisis.

PMID- 24860180
TI  - Paradoxical association of lipoprotein measures with incident atrial
      fibrillation.
AB  - BACKGROUND: Low-density lipoprotein (LDL) cholesterol is a strong risk factor for
      atherosclerosis but has an inverse association with atrial fibrillation (AF). We
      aimed to provide insight into the paradoxical association of LDL cholesterol with
      AF by evaluating the relationship of various lipoprotein measures and incident
      AF. METHODS AND RESULTS: We prospectively evaluated lipoprotein measures among 23
      738 healthy middle-aged and older women (median follow-up 16.4 years; N=795
      incident AF events). Baseline LDL cholesterol was directly measured, lipoprotein
      particle concentrations and size were measured by nuclear magnetic resonance
      spectroscopy, and apolipoproteins were measured by immunoassay. Cox regression
      models were adjusted for age, AF risk factors, inflammatory, and dysglycemic
      biomarkers. After multivariable adjustment, inverse associations with AF were
      observed (hazard ratio, 95% confidence interval for top versus bottom quintile, P
      value) for LDL cholesterol (0.72, 0.56-0.92, P=0.009), the total number of LDL
      particles (0.77, 0.60-0.99, P=0.045), and very-low-density lipoprotein particles
      (0.78, 0.61-0.99, P=0.04), which was driven by the number of cholesterol-poor
      small LDL (0.78, 0.61-1.00, P=0.05) and small very-low-density lipoprotein
      particles (0.78, 0.62-0.99, P=0.04). By contrast, the larger cholesterol-rich LDL
      particles and all high-density lipoprotein measures were not associated with AF
      in multivariable models. Adjustment for inflammatory and dysglycemic biomarkers
      had minimal impact on these associations. CONCLUSIONS: In this prospective study,
      the inverse association between LDL cholesterol and AF extended to several other
      atherogenic lipoproteins, and these associations are unlikely to be mediated by
      direct cholesterol effects. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov;
      Unique Identifier: NCT00000479.

PMID- 24860183
TI  - The challenges and opportunities of 'nudging'.

PMID- 24860184
TI  - Functional characterization of a new grapevine MYB transcription factor and
      regulation of proanthocyanidin biosynthesis in grapes.
AB  - A new regulator of proanthocyanidin (PA) biosynthesis in grapes was found by
      screening genes coordinately expressed with PA accumulation under different light
      conditions using a substantially improved method of serial analysis of gene
      expression (SuperSAGE). This R2R3-MYB transcription factor, VvMYBPAR, shows high
      protein sequence similarity with PA biosynthesis-regulating plant MYBs, such as
      VvMYBPA2 and TRANSPARENT TESTA2. Its transcript levels were relatively high in
      the skins of young berries, whereas the levels were higher in the seeds and at a
      maximum around veraison. In addition to its response to modified light
      conditions, the gene responded to abscisic acid application in the skins of
      cultured berries. Among the PA-specific branch genes, this transcript profile was
      not correlated with that of VvANR and VvLAR1 but was closely related to that of
      VvLAR2, suggesting different regulation of PA-specific branch genes from that of
      a known PA regulator, VvMYBPA2. The PA-specific regulation of VvMYBPAR was
      confirmed by VvMYBPAR constitutive expression in Arabidopsis in which the
      transgene specifically induced PA biosynthetic genes and resulted in PA
      accumulation in plants grown on sucrose-supplemented media to induce anthocyanin
      synthesis. A transient reporter assay using grapevine cells showed that VvMYBPAR
      activated the promoters on PA-specific branch genes and candidate genes
      associated with modification and transport of monomeric PA precursors, as well as
      the promoters of VvCHS3 and VvF3'5'Hd in the common flavonoid pathway, but not
      that of VvUFGT on the anthocyanin-specific branch. This new factor suggests the
      polygenic regulation of PA biosynthesis in grapes by closely related MYB
      transcription factors. 

PMID- 24860185
TI  - Increasing water use efficiency along the C3 to C4 evolutionary pathway: a
      stomatal optimization perspective.
AB  - C4 photosynthesis evolved independently numerous times, probably in response to
      declining atmospheric CO2 concentrations, but also to high temperatures and
      aridity, which enhance water losses through transpiration. Here, the
      environmental factors controlling stomatal behaviour of leaf-level carbon and
      water exchange were examined across the evolutionary continuum from C3 to C4
      photosynthesis at current (400 MUmol mol(-1)) and low (280 MUmol mol(-1))
      atmospheric CO2 conditions. To this aim, a stomatal optimization model was
      further developed to describe the evolutionary continuum from C3 to C4 species
      within a unified framework. Data on C3, three categories of C3-C4 intermediates,
      and C4 Flaveria species were used to parameterize the stomatal model, including
      parameters for the marginal water use efficiency and the efficiency of the CO2
      concentrating mechanism (or C4 pump); these two parameters are interpreted as
      traits reflecting the stomatal and photosynthetic adjustments during the C3 to C4
      transformation. Neither the marginal water use efficiency nor the C4 pump
      strength changed significantly from C3 to early C3-C4 intermediate stages, but
      both traits significantly increased between early C3-C4 intermediates and the C4
      like intermediates with an operational C4 cycle. At low CO2, net photosynthetic
      rates showed continuous increases from a C3 state, across the intermediates and
      towards C4 photosynthesis, but only C4-like intermediates and C4 species (with an
      operational C4 cycle) had higher water use efficiencies than C3 Flaveria. The
      results demonstrate that both the marginal water use efficiency and the C4 pump
      strength increase in C4 Flaveria to improve their photosynthesis and water use
      efficiency compared with C3 species. These findings emphasize that the advantage
      of the early intermediate stages is predominantly carbon based, not water
      related. 

PMID- 24860187
TI  - The non-catalytic N-terminal domain of ACS7 is involved in the post-translational
      regulation of this gene in Arabidopsis.
AB  - Post-transcriptional control of the expression of the 1-aminocyclopropane-1
      carboxylate synthase (ACS) gene family is important for maintaining appropriate
      levels of ethylene production. However, the molecular mechanism underlying the
      post-transcriptional regulation of type 3 ACS proteins remains unclear. Multiple
      sequence alignment revealed that the N-terminus of type 3 ACSs was longer than
      that of other ACSs. Fusing the N-terminal 54 residues of ACS7, the sole type 3
      ACS in Arabidopsis, to the beta-glucuronidase (GUS) reporter significantly
      decreased the stability of N(7(1-54))-GUS fusion protein. Among these 54
      residues, residues 1-14 conferred this negative effect on the GUS fusion gene.
      Consistently, a truncated form of ACS7 lacking residues 1-14 was more stable than
      full-length ACS7 when transgenically expressed in Arabidopsis and led to a more
      severe ethylene response phenotype in the light-grown transgenic seedlings.
      Interestingly, the ACS7 N-terminus had no effect on the stability of N(7)-GUS and
      ACS7 proteins at the etiolated seedling stage. Both exogenous 1-aminocyclopropane
      1-carboxylic acid (ACC) treatment and salt stress could rescue the levels of
      accumulation of N(7)-GUS fusion protein in light-grown seedlings. These results
      suggest that the non-catalytic N-terminus of ACS7 is involved in its own post
      translational regulation. The proteasome inhibitor MG132 suppressed degradation
      of full-length ACS7 in vivo, but had little effect on the N-terminal truncated
      form of ACS7, indicating that the N-terminus mediates the regulation of ACS7
      stability through the ubiquitin-26S proteasome pathway. 

PMID- 24860186
TI  - Activator- and repressor-type MYB transcription factors are involved in chilling
      injury induced flesh lignification in loquat via their interactions with the
      phenylpropanoid pathway.
AB  - Lignin biosynthesis and its transcriptional regulatory networks have been studied
      in model plants and woody trees. However, lignification also occurs in some
      fleshy fruit and has rarely been considered in this way. Loquat ( Eriobotrya
      japonica ) is one such convenient tissue for exploring the transcription factors
      involved in regulating fruit flesh lignification. Firmness and lignin content of
      'Luoyangqing' loquat were fund to increase during low-temperature storage as a
      typical symptom of chilling injury, while heat treatment (HT) and low-temperature
      conditioning (LTC) effectively alleviated them. Two novel EjMYB genes, EjMYB1 and
      EjMYB2, were isolated and were found to be localized in the nucleus. These genes
      responded differently to low temperature, with EjMYB1 induced and EjMYB2
      inhibited at 0  degrees C. They also showed different temperature responses under
      HT and LTC conditions, and may be responsible for different regulation of flesh
      lignification at the transcriptional level. Transactivation assays indicated that
      EjMYB1 and EjMYB2 are a transcriptional activator and repressor, respectively.
      EjMYB1 activated promoters of both Arabidopsis and loquat lignin biosynthesis
      genes, while EjMYB2 countered the inductive effects of EjMYB1. This finding was
      also supported by transient overexpression in tobacco. Regulation of
      lignification by EjMYB1 and EjMYB2 is likely to be achieved via their competitive
      interaction with AC elements in the promoter region of lignin biosynthesis genes
      such as Ej4CL1. 

PMID- 24860188
TI  - Differential impact of CD27 and 4-1BB costimulation on effector and memory CD8 T
      cell generation following peptide immunization.
AB  - The factors that determine differentiation of naive CD8 T cells into memory cells
      are not well understood. A greater understanding of how memory cells are
      generated will inform of ways to improve vaccination strategies. In this study,
      we analyzed the CD8 T cell response elicited by two experimental vaccines
      comprising a peptide/protein Ag and an agonist that delivers a costimulatory
      signal via CD27 or 4-1BB. Both agonists increased expansion of Ag-specific CD8 T
      cells compared with Ag alone. However, their capacity to stimulate
      differentiation into effector and memory cells differed. CD27 agonists promoted
      increased expression of perforin and the generation of short-lived memory cells,
      whereas stimulation with 4-1BB agonists favored generation of stable memory. The
      memory-promoting effects of 4-1BB were independent of CD4 T cells and were the
      result of programing within the first 2 d of priming. Consistent with this
      conclusion, CD27 and 4-1BB-stimulated CD8 T cells expressed disparate amounts of
      IL-2, IFN-gamma, CD25, CD71, and Gp49b as early as 3 d after in vivo activation.
      In addition, memory CD8 T cells, generated through priming with CD27 agonists,
      proliferated more extensively than did 4-1BB-generated memory cells, but these
      cells failed to persist. These data demonstrate a previously unanticipated link
      between the rates of homeostatic proliferation and memory cell attrition. Our
      study highlights a role for these receptors in skewing CD8 T cell differentiation
      into effector and memory cells and provides an approach to optimize vaccines that
      elicit CD8 T cell responses. 

PMID- 24860189
TI  - TCR Microclusters pre-exist and contain molecules necessary for TCR signal
      transduction.
AB  - TCR-dependent signaling events have been observed to occur in TCR microclusters.
      We found that some TCR microclusters are present in unstimulated murine T cells,
      indicating that the mechanisms leading to microcluster formation do not require
      ligand binding. These pre-existing microclusters increase in absolute number
      following engagement by low-potency ligands. This increase is accompanied by an
      increase in cell spreading, with the result that the density of TCR microclusters
      on the surface of the T cell is not a strong function of ligand potency. In
      characterizing their composition, we observed a constant number of TCRs in a
      microcluster, constitutive exclusion of the phosphatase CD45, and preassociation
      with the signaling adapters linker for activation of T cells and growth factor
      receptor-bound protein 2. The existence of TCR microclusters prior to ligand
      binding in a state that is conducive for the initiation of downstream signaling
      could explain, in part, the rapid kinetics with which TCR signal transduction
      occurs. 

PMID- 24860190
TI  - Unique temporal and spatial expression patterns of IL-33 in ovaries during
      ovulation and estrous cycle are associated with ovarian tissue homeostasis.
AB  - Ovaries are among the most active organs. Frequently occurring events such as
      ovulation and ovarian atresia are accompanied with tissue destruction and
      repairing. Critical roles of immune cells or molecules in those events have been
      well recognized. IL-33 is a new member of the IL-1 cytokine gene family. Recent
      studies suggest its roles beyond immune responses. We systemically examined its
      expression in ovaries for its potential roles in ovarian functions. During
      ovulation, a high level of IL-33 was transiently expressed, making it the most
      significantly upregulated immune gene. During estrous cycle, IL-33 expression
      levels fluctuated along with numbers of ovarian macrophages and atresia wave.
      Cells with nuclear form of IL-33 (nIL-33(+) cells) were mostly endothelial cells
      of veins, either in the inner layer of theca of ovulating follicles during
      ovulation, or surrounding follicles during estrous cycle. Changes in number of
      nIL-33(+) cells showed a tendency similar to that in IL-33 mRNA level during
      estrous cycle. However, the cell number sharply declined before a rapid increase
      of macrophages and a surge of atresia. The decline in nIL-33(+) cell number was
      coincident with detection of higher level of the cytokine form of IL-33 by
      Western blot, suggesting a release of cytokine form of IL-33 before the surge of
      macrophage migration and atresia. However, IL-33 Ab, either by passive transfer
      or immunization, showed a limited effect on ovulation or atresia. It raises a
      possibility of IL-33's role in tissue homeostasis after ovarian events, instead
      of a direct involvement in ovarian functions. 

PMID- 24860192
TI  - Does school suspension affect subsequent youth nonviolent antisocial behavior? A
      longitudinal study of students in Victoria, Australia and Washington State,
      United States.
AB  - School suspension has been not only associated with negative behaviours but is
      predictive of future poor outcomes. The current study investigates a) whether
      school suspension is a unique predictor of youth nonviolent antisocial behaviour
      (NVAB) relative to other established predictors, and b) whether the predictors of
      NVAB are similar in Australia and the United States (U.S.). The data analysed
      here draws on two state-wide representative samples of Grade 7 and 9 students in
      Victoria, Australia and Washington State, U.S., resurveyed at 12-month follow-up
      (N = 3,677, 99% retention). School suspension did not uniquely predict NVAB in
      the final model. The predictors of NVAB, similar across states, included previous
      student NVAB; current alcohol and tobacco use; poor family management;
      association with antisocial friends; and low commitment to school. An implication
      of the findings is that U.S. evidence-based prevention programs targeting the
      influences investigated here could be trialled in Australia.

PMID- 24860191
TI  - Astrocytic TGF-beta signaling limits inflammation and reduces neuronal damage
      during central nervous system Toxoplasma infection.
AB  - The balance between controlling infection and limiting inflammation is
      particularly precarious in the brain because of its unique vulnerability to the
      toxic effects of inflammation. Astrocytes have been implicated as key regulators
      of neuroinflammation in CNS infections, including infection with Toxoplasma
      gondii, a protozoan parasite that naturally establishes a chronic CNS infection
      in mice and humans. In CNS toxoplasmosis, astrocytes are critical to controlling
      parasite growth. They secrete proinflammatory cytokines and physically encircle
      parasites. However, the molecular mechanisms used by astrocytes to limit
      neuroinflammation during toxoplasmic encephalitis have not yet been identified.
      TGF-beta signaling in astrocytes is of particular interest because TGF-beta is
      universally upregulated during CNS infection and serves master regulatory and
      primarily anti-inflammatory functions. We report in this study that TGF-beta
      signaling is activated in astrocytes during toxoplasmic encephalitis and that
      inhibition of astrocytic TGF-beta signaling increases immune cell infiltration,
      uncouples proinflammatory cytokine and chemokine production from CNS parasite
      burden, and increases neuronal injury. Remarkably, we show that the effects of
      inhibiting astrocytic TGF-beta signaling are independent of parasite burden and
      the ability of GFAP(+) astrocytes to physically encircle parasites. 

PMID- 24860193
TI  - Dietary omega-3 fatty acids aid in the modulation of inflammation and metabolic
      health.
AB  - This article focuses on the role of omega-3 fatty acids as precursors for lipid
      signaling molecules known as oxylipins. Although omega-3 fatty acids are
      beneficial in autoimmune disorders, inflammatory diseases and heart disease, they
      are generally underrepresented in the American diet. A literature review confirms
      that the consumption of omega-3 fatty acids - whether in food sources such as
      walnuts, flax seeds and fatty fish (including salmon and sardines), or in
      supplements - is associated with decreased morbidity and mortality. This growing
      body of evidence, including the results of a recent study of patients with kidney
      disease, highlights the need to measure omega-3 fatty acids and their oxylipin
      products as markers of metabolic health and biomarkers of disease. In addition,
      there is substantial evidence of the need to increase the omega-3 fatty acid
      content of American diets to optimize metabolic health.

PMID- 24860194
TI  - Vocabulary and Reading Comprehension: Direct, Indirect, and Reciprocal
      Influences.

PMID- 24860196
TI  - Enhancement of CO2 Affinity in a Polymer of Intrinsic Microporosity by Amine
      Modification.
AB  - Nitrile groups in the polymer of intrinsic microporosity PIM-1 were reduced to
      primary amines using borane complexes. In adsorption experiments, the novel amine
      PIM-1 showed higher CO2 uptake and higher CO2/N2 sorption selectivity than the
      parent polymer, with very evident dual-mode sorption behavior. In gas permeation
      with six light gases, the individual contributions of solubility and diffusion to
      the overall permeability was determined via time-lag analysis. The high CO2
      affinity drastically restricts diffusion at low pressures and lowers CO2
      permeability compared to the parent PIM-1. Furthermore, the size-sieving
      properties of the polymer are increased, which can be attributed to a higher
      stiffness of the system arising from hydrogen bonding of the amine groups. Thus,
      for the H2/CO2 gas pair, whereas PIM-1 favors CO2, amine-PIM-1 shows
      permselectivity toward H2, breaking the Robeson 2008 upper bound.

PMID- 24860198
TI  - BRICKS AND MORTAR CLIENTELISM: Sectarianism and the Logics of Welfare Allocation
      in Lebanon.

PMID- 24860197
TI  - Analysis of Variance of Multiply Imputed Data.
AB  - As a procedure for handling missing data, Multiple imputation consists of
      estimating the missing data multiple times to create several complete versions of
      an incomplete data set. All these data sets are analyzed by the same statistical
      procedure, and the results are pooled for interpretation. So far, no explicit
      rules for pooling F-tests of (repeated-measures) analysis of variance have been
      defined. In this paper we outline the appropriate procedure for the results of
      analysis of variance for multiply imputed data sets. It involves both
      reformulation of the ANOVA model as a regression model using effect coding of the
      predictors and applying already existing combination rules for regression models.
      The proposed procedure is illustrated using three example data sets. The pooled
      results of these three examples provide plausible F- and p-values.

PMID- 24860195
TI  - A Population-Based Study of Alcohol Use in Same-Sex and Different-Sex Unions.
AB  - The present study advances research on union status and health by providing a
      first look at alcohol use differentials among different-sex and same-sex married
      and cohabiting individuals using nationally representative population-based data
      (National Health Interview Surveys 1997-2011, N = 181,581). The results showed
      that both same-sex and different-sex married groups reported lower alcohol use
      than both same-sex and different-sex cohabiting groups. The results further
      revealed that same-sex and different-sex married individuals reported similar
      levels of alcohol use, whereas same-sex and different-sex cohabiting individuals
      reported similar levels of alcohol use. Drawing on marital advantage and minority
      stress approaches, the findings suggest that it is cohabitation status-not same
      sex status-that is associated with elevated alcohol rates.

PMID- 24860200
TI  - The effects of native language on Indian English sounds and timing patterns.
AB  - This study explored whether the sound structure of Indian English (IE) varies
      with the divergent native languages of its speakers or whether it is similar
      regardless of speakers' native languages. Native Hindi (Indo-Aryan) and Telugu
      (Dravidian) speakers produced comparable phrases in IE and in their native
      languages. Naive and experienced IE listeners were then asked to judge whether
      different sentences had been spoken by speakers with the same or different native
      language backgrounds. The findings were an interaction between listener
      experience and speaker background such that only experienced listeners
      appropriately distinguished IE sentences produced by speakers with different
      native language backgrounds. Naive listeners were nonetheless very good at
      distinguishing between Hindi and Telugu phrases. Acoustic measurements on
      monophthongal vowels, select obstruent consonants, and suprasegmental temporal
      patterns all differentiated between Hindi and Telugu, but only 3 of the measures
      distinguished between IE produced by speakers of the different native languages.
      The overall results are largely consistent with the idea that IE has a target
      phonology that is distinct from the phonology of native Indian languages. The
      subtle L1 effects on IE may reflect either the incomplete acquisition of the
      target phonology or, more plausibly, the influence of sociolinguistic factors on
      the use and evolution of IE.

PMID- 24860201
TI  - Mediators of Stereotype Threat among Black College Students.
AB  - We hypothesize that the manner in which stereotype threat affects college grade
      achievement is mediated by institutional context as well as individual
      characteristics. Drawing on a sample of black students from the National
      Longitudinal Survey of Freshmen we find weak and inconsistent evidence that
      institutional characteristics influence the operation of stereotype threat. We
      find more consistent evidence to indicate that the effect of stereotype threat is
      conditioned by individual factors such as skin color, multiracial origins, and an
      integrated upbringing. Most of the effect on grade achievement occurs through the
      internalization pathway, in which the internalization of negative stereotypes
      leads to disinvestment manifested by a reduction in academic effort. The
      reduction in work effort, in turn, lowers grades. We also find evidence that
      immigrant origin confers protection from the negative effects of stereotype
      threat through both internalization and externalization mechanisms, though the
      ultimate effect of grade achievement is rather small.

PMID- 24860202
TI  - Social Context of Disabled Parenting.
AB  - The article discusses parenting of individuals with disability. It was based on
      the perspective of barriers, which (next to the perspective of risk and the
      functional perspective) marks the nature of discourse this theme takes in the
      literature on the subject and in practice. The perspective of barriers, related
      to the social model of disability, emphasizes the social factors important for
      the quality of parenting of individuals with disability. These factors were
      analyzed on the basis of available research results with mothers and fathers with
      disability, and able-bodied individuals who are part of their professional and
      non-professional environment. The article draws attention to the specificity of
      socialization of individuals with disability and its significance for
      preparations for family roles, social attitudes towards disabled individuals'
      parenting, and their determinants. It also presents disabled parents' experiences
      and the importance of realizing their role of a mother or father.

PMID- 24860199
TI  - The Influence of Major Life Events on Economic Attitudes in a World of Gene
      Environment Interplay.
AB  - The role of "genes" on political attitudes has gained attention across
      disciplines. However, person-specific experiences have yet to be incorporated
      into models that consider genetic influences. Relying on a gene-environment
      interplay approach, this study explicates how life-events, such as losing one's
      job or suffering a financial loss, influence economic policy attitudes. The
      results indicate genetic and environmental variance on support for unions,
      immigration, capitalism, socialism and property tax is moderated by financial
      risks. Changes in the magnitude of genetic influences, however, are temporary.
      After two years, the phenotypic effects of the life events remain on most
      attitudes, but changes in the sources of individual differences do not.
      Univariate twin models that estimate the independent contributions of genes and
      environment on the variation of attitudes appear to provide robust baseline
      indicators of sources of individual differences. These estimates, however, are
      not event or day specific. In this way, genetic influences add stability, while
      environment cues change, and this process is continually updated.

PMID- 24860204
TI  - Design of a secondary ionization target for direct production of a C- beam from
      CO2 pulses for online AMS.
AB  - We designed and optimized a novel device "target" that directs a CO2 gas pulse
      onto a Ti surface where a Cs+ beam generates C- from the CO2. This secondary
      ionization target enables an accelerator mass spectrometer to ionize pulses of
      CO2 in the negative mode to measure 14C/12C isotopic ratios in real time. The
      design of the targets were based on computational flow dynamics, ionization
      mechanism and empirical optimization. As part of the ionization mechanism, the
      adsorption of CO2 on the Ti surface was fitted with the Jovanovic-Freundlich
      isotherm model using empirical and simulation data. The inferred adsorption
      constants were in good agreement with other works. The empirical optimization
      showed that amount of injected carbon and the flow speed of the helium carrier
      gas improve the ionization efficiency and the amount of 12C- produced until
      reaching a saturation point. Linear dynamic range between 150 and 1000 ng of C
      and optimum carrier gas flow speed of around 0.1 mL/min were shown. It was also
      shown that the ionization depends on the area of the Ti surface and Cs+ beam
      cross-section. A range of ionization efficiency of 1-2.5% was obtained by
      optimizing the described parameters.

PMID- 24860203
TI  - Companionship in the neighborhood context: older adults' living arrangements and
      perceptions of social cohesion.
AB  - This study investigated the impact of neighborhood social cohesion on the
      perceived companionship of nearly 1,500 community-dwelling older adults from the
      Neighborhood, Organization, Aging and Health project (NOAH), a Chicago-based
      study of older adult well-being in the neighborhood context. We hypothesized that
      the relationship between neighborhood-level social cohesion and individual
      residents' reports of companionship would be more pronounced among those who
      lived alone than those who resided with others. Controlling for age, gender,
      education, race, marital status, length of neighborhood residence, and self-rated
      health, neighborhood social cohesion predicted companionship among those who
      lived alone; for a one-unit increase in neighborhood social cohesion, the odds of
      reporting companionship increased by half. In contrast, social cohesion did not
      predict the companionship of those who resided with others. The results suggest
      that older adults who live alone particularly profit from the benefits of
      socially cohesive neighborhood environments. 

PMID- 24860205
TI  - Student and school factors associated with school suspension: A multilevel
      analysis of students in Victoria, Australia and Washington State, United States.
AB  - One of the common issues schools face is how best to handle challenging student
      behaviors such as violent behavior, antisocial behavior, bullying, school rule
      violations, and interrupting other students' learning. School suspension may be
      used to remove students engaging in challenging behaviors from the school for a
      period of time. However, the act of suspending students from school may worsen
      rather than improve their behavior. Research shows that suspensions predict a
      range of student outcomes, including crime, delinquency, and drug use. It is
      therefore crucial to understand the factors associated with the use of school
      suspension, particularly in sites with different policy approaches to problem
      behaviors. This paper draws on data from state-representative samples of 3,129
      Grade 7 and 9 students in Washington State, United States and Victoria, Australia
      sampled in 2002. Multilevel modeling examined student and school level factors
      associated with student-reported school suspension. Results showed that both
      student (being male, previous student antisocial and violent behavior,
      rebelliousness, academic failure) and school (socioeconomic status of the school,
      aggregate measures of low school commitment) level factors were associated with
      school suspension and that the factors related to suspension were similar in the
      two states. The implications of the findings for effective school behavior
      management policy are that, rather than focusing only on the student, both
      student and school level factors need to be addressed to reduce the rates of
      school suspension.

PMID- 24860206
TI  - Emotion control during later life: The relationship between global perceptions
      and daily experience.
AB  - The extent to which individuals generally believe that they can successfully
      manage their emotions is related to healthy coping and well-being. Nevertheless,
      it is unclear how this general belief is related to daily affective experiences.
      In the current study, the relationship between global emotion control beliefs and
      daily affect reports across 56 days were assessed in a sample of 298 older
      adults. Results indicate that higher global emotion control beliefs were related
      to lower mean daily negative affect and higher mean daily positive affect.
      Additionally, variability analyses investigating multiple potential time scales
      revealed that global beliefs were related to lower variance in daily negative
      affect and less variable speeds of daily negative affect change across a range of
      time scales (from windows of 3 days to windows of approximately 2 weeks).
      Alternatively, global control beliefs were not significantly related to variance
      in daily positive affect or variance in speeds of daily positive affect change.
      Together, results suggest that global emotion control beliefs predict average
      experience of daily affect and variability in daily negative affect.

PMID- 24860207
TI  - Irritability as a criterion in diagnosis of child and adolescent bipolar
      disorder: thorny road ahead.

PMID- 24860208
TI  - Evidence based psychosocial interventions in substance use.
AB  - In recent years, there has been significant progress and expansion in the
      development of evidence-based psychosocial treatments for substance abuse and
      dependence. A literature review was undertaken using the several electronic
      databases (PubMed, Cochrane Database of systemic reviews and specific journals,
      which pertain to psychosocial issues in addictive disorders and guidelines on
      this topic). Overall psychosocial interventions have been found to be effective.
      Some interventions, such as cognitive behavior therapy, motivational interviewing
      and relapse prevention, appear to be effective across many drugs of abuse.
      Psychological treatment is more effective when prescribed with substitute
      prescribing than when medication or psychological treatment is used alone,
      particularly for opiate users. The evidence base for psychological treatment
      needs to be expanded and should also include research on optimal combinations of
      psychological therapies and any particular matching effects, if any.
      Psychological interventions are an essential part of the treatment regimen and
      efforts should be made to integrate evidence-based interventions in all substance
      use disorder treatment programs. 

PMID- 24860210
TI  - Hypothyroidism and bipolar affective disorder: is there a connection?
AB  - CONTEXT: Hypothalamic-pituitary-thyroid axis dysfunction in the pathophysiology
      of bipolar disorder has received less attention as compared with that in
      depressive disorder. AIMS: To study the prevalence of hypothyroidism in patients
      diagnosed with bipolar disorder and compare it with a population norm. SETTINGS
      AND DESIGN: The setting was the psychiatry inpatient unit of a tertiary care
      hospital. The design was retrospective and observational. SUBJECTS AND METHODS: A
      retrospective observational study was performed, referring to the case records of
      84 cases of bipolar disorder admitted to the Department of Psychiatry in a
      Tertiary Referral Center during the year 2010-2012. The prevalence of
      hypothyroidism both subclinical as demonstrated by elevated thyroid stimulating
      hormone (TSH) levels (cut-off value 4.2 MUU/ml) and overt hypothyroidism (fasting
      T4 <0.92 ng/dl and TSH >4.2 MUU/ml) was calculated. This was compared with the
      population prevalence of hypothyroidism as determined by an epidemiological study
      carried out in the year 2009, in the same region. The correlation between
      hypothyroidism, gender, lithium prophylaxis and family history of mood disorder
      was computed. STATISTICAL ANALYSIS: Percentage prevalence of hypothyroidism in
      the sample was calculated and compared to a population norm. The correlation
      between hypothyroidism, gender, lithium prophylaxis and family history of mood
      disorder was computed using the odds ratio (OR). RESULTS: The total prevalence of
      hypothyroidism in both males and females in the bipolar group was comparable with
      that in the general population. There is a significant association between family
      history of mood disorder in first degree relatives and patients having
      hypothyroidism (OR 5.504 and P = 0.012). There were no statistically significant
      associations between thyroid abnormalities and age, duration of illness and
      lithium prophylaxis. CONCLUSIONS: There is no significant association between
      hypothyroidism and bipolar disorder. Family history of mood disorder and
      hypothyroidism show significant association. (OR -5.504 AND P = 0.012).

PMID- 24860209
TI  - Religion, spirituality, and schizophrenia: a review.
AB  - Religion and spirituality exert a significant role in the lives of many
      individuals, including people with schizophrenia. However, the contribution of
      religion and spirituality to various domains (psychopathology, explanatory
      models, treatment seeking, treatment adherence, outcome, etc.) has not received
      much attention. In this article, we review the exiting data with regards to the
      relationship of religion, spirituality, and various domains in patients with
      schizophrenia. Available evidence suggests that for some patients, religion
      instills hope, purpose, and meaning in their lives, whereas for others, it
      induces spiritual despair. Patients with schizophrenia also exhibit religious
      delusions and hallucinations. Further, there is some evidence to suggest that
      religion influences the level of psychopathology. Religion and religious
      practices also influence social integration, risk of suicide attempts, and
      substance use. Religion and spirituality also serves as an effective method of
      coping with the illness. Religion also influences the treatment compliance and
      outcome in patients with schizophrenia. 

PMID- 24860212
TI  - Consultation-liaison Approach for the Management of Psychiatric Manifestations in
      Parkinson's Disease and Related Disorders: A Report from Neuropsychiatric
      Hospital, India.
AB  - BACKGROUND: Non-motor psychiatric manifestations of Parkinson's disease have been
      increasingly noted to contribute to morbidity and mortality. MATERIALS AND
      METHODS: We studied the psychiatric manifestations among inpatients with
      Parkinson's disease and other movement disorders by examining the referrals (N =
      127) to consultation-liaison psychiatry services from neurology/neurosurgery
      between July 2009 and April 2010 using structured clinical proforma. RESULTS:
      Parkinson's disease and other movement disorders was the most common neurological
      diagnosis (19%). The most common reason for referral was depression (38%)
      followed by behavioral problems (33%). Post-assessment, depression rates were
      higher (54%) and behavioral manifestations were diagnosed as sleep problems
      (13%), organic psychiatric syndrome (13%), psychosis (8%), anxiety and obsessive
      compulsive disorder (8%), nil psychiatry (4%). CONCLUSION: Psychiatric
      comorbidity is high among in-patients with movement disorders and affective
      changes are common. Timely assessment using structured clinical proforma would
      help in enhanced detection of depression in patients with movement disorders.

PMID- 24860211
TI  - A controlled study of serum lipid profiles in Indian patients with depressive
      episode.
AB  - BACKGROUND: Lower levels of circulating lipid fractions and cholesterol are risk
      factors for impulsivity and depressive disorder. A lower level of serum
      cholesterol is also associated with patients presenting with history of self
      harm. MATERIALS AND METHODS: A total of 30 depressive patients and 30 healthy
      matched control subjects were recruited from the department of Psychiatry of a
      tertiary care hospital. We measured serum total cholesterol (TC), low-density
      lipoprotein (LDL) and high-density lipoprotein cholesterol and triglyceride
      levels of both patient and control group. RESULTS: The serum TC and LDL
      cholesterol levels were found to be significantly lower in study group than that
      of control group. CONCLUSION: Lower levels of serum cholesterol are associated
      with depressive disorder.

PMID- 24860213
TI  - Expressed emotions in patients with obsessive compulsive disorder: a case control
      study.
AB  - BACKGROUND: Expressed emotion (EE) is the attitude that the relatives show
      towards the illness and the person. EE is identified as a direct factor in the
      relapse of patients with psychological disorders. Literature on EE in anxiety
      disorders is limited. Role of EE in obsessive compulsive disorder (OCD) may help
      in better understanding of the role of social factors in OCD. AIM: To compare EE
      in patients with OCD and compare with controls. MATERIALS AND METHODS: The sample
      included 30 cases and 30 age and sex matched controls. The patients were
      diagnosed as having OCD using International Classification of Diseases-10
      Diagnostic Criteria for Research (ICD-10 DCR) criteria. Yale-Brown Obsessive
      Compulsive Scale (Y-BOCS) was used to assess severity of OCD among patients.
      General health questionnaire (GHQ) was used to rule out any psychiatric disorder
      among control population. EE was assessed in cases and controls using Family
      Emotional Involvement and Criticism Scale (FEICS). Chi-square test and t-test
      were used to assess the difference between two groups. RESULTS: OCD patients in
      comparison controls had significantly increased total FEICS score (P = 0.001).
      There was an increase in both subscales of perceived criticism (PC) with P =
      0.001 and emotional involvement (EI) with P = 0.001 in patients with OCD than
      controls. CONCLUSION: EE are significantly increased in patients with OCD. EE
      should be assessed regularly in patients with OCD.

PMID- 24860214
TI  - Mortality among inpatients of a psychiatric hospital: Indian perspective.
AB  - OBJECTIVE: The objective of this study is to assess mortality and its correlates
      among psychiatric inpatients of a tertiary care neuropsychiatric hospital. Given
      the background that such a study has never been undertaken in India, the findings
      would have a large bearing on policy making from a mental health-care
      perspective. MATERIALS AND METHODS: The medical records of those psychiatric
      inpatients (n = 333) who died during their stay at the National Institute of
      Mental Health and Neurosciences in past 26 years (January 1983 to December 2008)
      constituted the study population. RESULTS: During the 26 years, there were a
      total of 103,252 psychiatric in-patient admissions, out of which 333 people died
      during their inpatient stay. Majority (n = 135, 44.6%) of the mortality was seen
      in the age group of 21-40 years. Most of the subjects were males (n = 202, 67%),
      married (n = 172, 56.8%) and from urban areas (n = 191, 63%). About, 54% of the
      subjects had short inpatient stay (<5 days, median for the sample). In 118 (39%)
      of the subjects, there was a history of physical illness. Leading cause of death
      were cardiovascular system disorders (n = 132, 43.6%), followed by respiratory
      system disorders (n = 45, 14.9%), nervous system disorders (n = 30, 9.9%) and
      infections (n = 31, 10.1%). In 21 (7%), cause of death was suicide. CONCLUSIONS:
      Identifying the factors associated with the death of inpatients is of utmost
      importance in assessing the care in a neuropsychiatric hospital and in
      formulating better treatment plan and policy in mental health. The discussion
      focuses on the analysis of different factors associated with inpatient mortality.

PMID- 24860215
TI  - Sexual Crime in India: Is it Influenced by Pornography?
AB  - PURPOSE: Studies on whether pornography poses a greater risk for sexually
      aggressive behavior have revealed conflicting results. This study aims to examine
      the relationship between the consumption of pornography and the subsequent
      increase in sexual violence, thus testing the hypothesis that increase in
      consumption of pornography is related to increased sexual crime, in the Indian
      scenario. MATERIALS AND METHODS: The current study explored the association
      between reported incidence of crime over a period of four decades - 1971-2008
      (time periods being divided into: Pre-liberalization and post-liberation - India
      adopted liberalization policy in 1992) and availability of pornography over
      internet with a particular focus on crime against women (such as rape, sexual
      harassment, and crime against women). RESULTS: Comparison of pre-liberalization
      and post-liberalization growth of rape rates was not significant. Though there
      were statistically significant positive correlations between the number of
      internet users and sexual crime rates, the association was non-significant after
      controlling for the effects of population growth using regression analysis.
      CONCLUSION: Results presented needs to be interpreted with extreme care and
      caution. Nevertheless, the results from this study suggest that easy access to
      pornography did not have a significant impact on rape rates and crime rate
      against women.

PMID- 24860216
TI  - Socio-emotional factors in alcohol dependence.
AB  - BACKGROUND: Alcohol-dependent patients are traditionally believed to have
      insecure attachment styles, higher anger expression, and lower self-esteem. There
      is a need to study them together. AIM: To understand the relationships amongst
      various of the socio-emotional factors. MATERIALS AND METHODS: Forty male
      patients with Alcohol dependence syndrome and 40 matched healthy controls
      (General Health Questionnaire-12 score <3) were compared on attachment styles (on
      Relationship Scale Questionnaire), anger domains (on State Trait Anger Expression
      Inventory), and self-esteem (on Rosenberg Self-esteem Scale). STATISTICS AND
      ANALYSIS: Comparison using independent samples t test and chi square test;
      correlation using Pearson's correlation coefficient. RESULTS: Patients had
      significantly higher anger expression, 'anger in' and 'anger out,' and lower self
      esteem than healthy controls. Severity of alcohol dependence had significant
      correlation with 'anger out,' and self-esteem had significant negative
      correlation with anger expression. CONCLUSION: The present study suggests that
      the socio-emotional factors studied are developmentally linked to each other.

PMID- 24860217
TI  - A Placebo Controlled Trial on Add-on Modafinil on the Anti-psychotic Treatment
      Emergent Hyperglycemia and Hyperlipidemia.
AB  - Modafinil is non stimulant drug which is marketed for mainly Narcolepsy and
      daytime drowsiness. The clinical experience and Summary of Product
      Characteristics (SPC) of the drug also mentions Anorexia as one of the side
      effects. Anorexia can have a direct impact on the carbohydrate and fat intake,
      which may, in turn, regulate antipsychotic induced dyslipidemia and
      Hyperglycaemia. AIM: To compare the effects of Modafinil- ADDON with Placebo add
      on with olanzapine, Clozapine and Risperidone in drug naive subjects and people
      who were started on the drugs within 15days of assessment. MATERIALS AND METHODS:
      Randomized, Double blind, Placebo controlled study, which was conducted at two
      centres, one at department of Psychiatry, S.V Medical College, Tirupati and the
      other at Asha hospitals, Hyderabad. Seventy two patient were randomised, sixty
      three patients have completed the total study period of three months. The dose of
      Modafinil was 200 mgs constantly as Flexible doses of Olanzapine, Clozapine and
      Risperidone as per clinical need was given. A baseline, three week and twelve
      week assessments of Fasting blood Glucose and fasting Serum cholesterol were made
      and the groups were compared on these parameters. RESULTS: From baseline to week
      3 there was a significant raise in Fasting serum cholesterol followed by a fall
      from week 3 to week 12 in the Modafinil addon group, though it could not be
      considered a drug for hypercholesteremia like Statins in controlling
      hyperlipidaemia. The implications of these findings were discussed.

PMID- 24860218
TI  - Visual Image-Induced Craving for Ethanol (VICE): Development, Validation, and a
      Pilot fMRI Study.
AB  - BACKGROUND: Craving induction in a controlled environment is helpful in the
      research of craving mechanism and its role in development of alcohol dependence
      (AD). We describe a novel tool Visual Image-induced Craving for Ethanol (VICE)
      and its effects on brain activation with pilot functional magnetic resonance
      imaging (fMRI). MATERIALS AND METHODS: Alcohol-related visual cues (ARCs) in 5
      scenarios were photographed, which included pictures of bars, alcoholic beverage
      bottles, pouring of alcohol into glasses, glasses filled with alcohol, and scenes
      of people sipping alcohol, counterbalanced with neutral pictures (involving
      water, milk etc.,). Craving scores were obtained from 15 hospitalized patients
      with AD to validate this tool. In the pilot fMRI (3-Tesla) study, 5 patients were
      examined using VICE in a symptom provocation model. Group level-fixed effect
      analysis of brain activation differences was done using SPM8. RESULTS: VICE
      showed a high internal consistency with Cronbach's alpha coefficient of 0.86,
      which confirmed its reliability. Concurrent validity of VICE was demonstrated via
      its convergence with the Penn Alcohol Craving Scale. ARCs had significantly
      greater mean craving scores than neutral cues in all the 5 scenarios (intentional
      validity). In the pilot fMRI, patients were found to have greater activation
      while viewing ARCs compared to the neutral cues in right insular cortex and
      deficient activation in right orbitofrontal cortex. CONCLUSIONS: The VICE is a
      reliable and valid measure of alcohol craving with promising clinical and
      translational research implications. Preliminary fMRI findings indicate it can be
      used as a symptom provocation tool for fMRI experiments.

PMID- 24860219
TI  - Olanzapine discontinuation emergent recurrence in bipolar disorder.
AB  - OBJECTIVE: The efficacy of atypical antipsychotics including olanzapine in acute
      treatment of manic episode has been established, whereas its role in maintenance
      treatment is not clear. MATERIALS AND METHODS: Thirteen patients of bipolar
      disorder who were on regular treatment with mood stabilizer and subsequently
      relapsed into mania or depressive episode after discontinuation of olanzapine
      were studied for various socio-demographic and clinical factors using
      retrospective chart review. RESULTS: There was no correlation found between the
      period of tapering olanzapine, time to recurrence of episode after
      discontinuation, and the dosage of olanzapine at the time of discontinuation. The
      predominant early signs of relapse after discontinuation of olanzapine included
      sleep disturbance (72.7%), lack of insight for change in behavior (72.7%),
      irritability (54.5%), and elevated mood (45.5%). CONCLUSION: Mood stabilizer
      alone as a maintenance therapy of bipolar disorder may be inadequate for long
      term management. A low dose of olanzapine along with mood stabilizers might be
      useful for prevention of recurrence in bipolar disorder.

PMID- 24860220
TI  - Profile of nicotine use among alcohol dependent patients visiting a tertiary care
      center in north India.
AB  - BACKGROUND: Use of tobacco among alcohol dependent population is quite frequent.
      This co-morbidity increases the risk for various diseases. Understanding the
      pattern of tobacco use with co-morbid alcohol use may help in planning
      appropriate prevention/treatment strategies. The study aimed at examining the
      profile and pattern of nicotine use among alcohol dependent patients visiting a
      tertiary care treatment center in North India. MATERIALS AND METHODS: Male
      patients fulfilling diagnostics and statistical manual of mental disorder fourth
      edition, criteria for nicotine and alcohol diagnostics and statistical
      dependence, attending the out-patient department of the tertiary care treatment
      center were recruited after obtaining informed consent. The socio-demographic
      profile, drug use history, nicotine associated health problems and general health
      problem were recorded. Motivation to stop tobacco use was assessed qualitatively
      using the direct questions about their interest and intentions to quit. RESULTS:
      A total of 150 subjects were included in the study. The mean age of the study
      sample was 37.6 +/- 10.44 years. Tobacco was reported as the gateway drug in 90%
      of the cases. Exclusive bidi use reported in 42% of the subjects. Mean duration
      of bidi and co-morbid alcohol use was higher than cigarette or smokeless tobacco
      use. Self-reported health problems associated with nicotine use and general
      health was reported by 41% and 39% of the subjects. Unsuccessful past quit
      attempts was present in 85% cases. More than 90% of subjects remained interested
      in quitting the tobacco use. An increased liver enzyme (aspartate transaminase,
      alanine transaminase and gamma-glutamyl transferase) were observed in 43, 32 and
      47% of the cases. CONCLUSION: The results suggest the nicotine and alcohol
      dependent patients represent a separate population requiring higher attention
      from the treating physician.

PMID- 24860221
TI  - Domestic violence as a risk factor for maternal depression and neonatal outcomes:
      a hospital-based cohort study.
AB  - OBJECTIVES: This study attempted to follow up a cohort of women who presented to
      a tertiary hospital to investigate the effect of domestic violence on maternal
      and neonatal outcomes. MATERIALS AND METHODS: Women, between 26-34 weeks of
      gestation, attending the obstetrics outpatient department, were recruited and
      followed up until delivery. They were assessed at recruitment and after delivery
      using the Edinburgh Postnatal Depression Scale, the Abuse Assessment Screen, and
      a pro forma to assess socio-demographic and clinical characteristics. Bivariate
      and multivariate statistics were employed to assess statistical significance.
      RESULTS: One hundred and fifty women were recruited, 132 delivered in the
      hospital and were followed up. Domestic violence was associated with antenatal
      and postnatal depression, spouse's insistence of a boy baby, medical
      complications during pregnancy, preterm delivery, and lower birth-weight.
      CONCLUSION: Domestic violence has a significant impact on maternal and neonatal
      outcomes. Screening for domestic violence and interventions should be part of all
      antenatal programs. India should also employ public health approaches to change
      its patriarchal culture.

PMID- 24860222
TI  - Symptoms specificity of anxiety sensitivity dimensions in korean adults.
AB  - CONTEXT: Relation of three dimensions of anxiety sensitivity (AS) (physical
      concerns [PC], cognitive concerns [CC] and social concerns [SC]) with anxiety or
      depression has been inconsistently reported. One possible explanation on the
      mixed findings is the lack of reliable measurement that assesses AS dimensions.
      AIMS: This study was aimed to examine the specificity of dimensions of AS to
      anxiety and depression in a sample of Korean adults. SETTINGS AND DESIGN:
      Participants included 426 Korean adults who were recruited by means of
      advertisements requesting volunteers for the psychological assessments. MATERIALS
      AND METHODS: Participants completed measures of AS, anxious symptoms and
      depressive symptoms. STATISTICAL ANALYSIS: Linear regression equations were
      constructed. RESULTS: It was found that PC and SC showed specificity to anxiety
      after adjusting for depression, while CC showed specificity to depression after
      controlling for anxiety. CONCLUSIONS: The findings suggest specificity of PC and
      SC to anxiety and of CC to depression when their relationship was explored with
      the more reliable measurement. The present findings clarify the nature of
      dimensions of AS in Korean adults.

PMID- 24860223
TI  - The diagnostic accuracy and validity of the teen screen questionnaire-mental
      health for clinical and epidemiological studies in primary-care settings.
AB  - BACKGROUND: To validate a brief, self-reported, Teen Symptom Questionnaire-Mental
      Health (TSQ-M), for identifying adolescents with mental ill-health, designed for
      conducting epidemiological studies and clinical work in primary-care settings.
      MATERIALS AND METHODS: In this prospective, cross-sectional study of 146
      adolescents, re-cruited six rural and urban schools, the newly developed TSQ-M as
      the measure for validation and General Health Questionnaire-12 item (GHQ-12) as
      the gold standard measure were administered by independent trained raters. Tests
      for diagnostic accuracy and validity were conducted. RESULTS: A TSQ-M score of
      >=29 (Sn=75.68%, Sp=68.06, +LR=2.37, -LR=0.36, PPV=70.9, NPV=73.1) with the AUC
      of 0.79, is suggested for screening use in Indian populations. Besides the
      adequate face and content validity, TSQ-M has moderate internal consistency
      (Cronbach's alpha = .64) suggesting that the construct of mental ill-health as
      conceptualized by TSQ-M has multiple sub-constructs. The presence of sub
      constructs was demonstrated by an 8- factor structure, which explained 60% of
      variance. CONCLUSION: The TSQ-M is a psychometrically adequate, yet a brief
      measure, for clinical and research work in identifying mental ill-health among
      adolescents in primary-care settings in India.

PMID- 24860224
TI  - Psychosis in a case of kleine-levin syndrome: a diagnostic challenge.
AB  - Kleine-Levin syndrome (KLS) is a rare disorder of sleep diagnosed mainly on
      clinical grounds. It presents a unique diagnostic dilemma for neurologists and
      psychiatrists; especially due to a high risk of being diagnosed as a psychiatric
      condition like a mood disorder. However, there is literature available
      documenting the cooccurrence of psychiatric illnesses in patients diagnosed with
      KLS. The following case highlights the above points. 

PMID- 24860225
TI  - Use of electroconvulsive therapy in an adolescent patient with catatonia.
AB  - There is lot of skepticism about the use of electroconvulsive therapy (ECT) in
      children and adolescents. However, available literature suggests that use of ECT
      can be at times life-saving in adolescents, especially those presenting with
      severe catatonia. We treated a 16-year-old female who presented to us with
      catatonia with a course of nine ECTs, with which she showed marked improvement.
      Review of the literature suggests that ECT should be considered as the second
      line treatment in the management of catatonia in adolescents. 

PMID- 24860226
TI  - Fetishistic transvestism in a patient with mental retardation and psychosis.
AB  - Fetishistic transvestism is a disorder of sexual preference associated with
      fantasies and sexual urges to dress in opposite gender clothing as a means of
      arousal and as an adjunct to masturbation and coitus. The disorder has been
      reported in people with learning disabilities. The disorder has been reported in
      a young male with dull normal intelligence. Transvestism though has been
      described in schizophrenia and psychosis and fetishism has been described in the
      course of simple schizophrenia, there are no reports of fetishistic transvestism
      in a patient with mental retardation and psychosis. A case of fetishistic
      transvestism in a patient with mental retardation and psychosis with treatment
      and relevant review of literature is reported. 

PMID- 24860227
TI  - Induction of response to psychotropic medications in depression and panic after
      concurrent treatment of diabetes.
AB  - We present a case of depression with panic disorder, which did not respond to
      adequate psychiatric interventions over a period of several months. However, it
      improved completely with the diagnosis and treatment of diabetes mellitus. Hence,
      we infer that comorbid diabetes mellitus can render depression resistant to
      psychiatric interventions and must always be ruled out when treating patients who
      show poor response to adequate interventions for an adequate period of time. The
      role of antidepressants should also be considered in poor glycemic control. 

PMID- 24860228
TI  - Child's Play: Therapist's Narrative.
AB  - Play has been recognized as an essential component to children's healthy
      development. Schools of play therapy differ philosophically and technically, but
      they all embrace the therapeutic and developmental properties of play. This case
      report is an illustration of how a 6-year-old child with emotional disorder was
      facilitated to express concerns in child-centered play therapy. The paper
      discusses the therapist's narration of the child's play. 

PMID- 24860229
TI  - Very Late-onset Schizophrenia Like Psychosis: Case Series and Future Directions.
AB  - The quest to unravel the mysteries of schizophrenia has led to immense research
      in this area over the years. Previously schizophrenia was considered to strictly
      be an early onset disorder. However, the heralding of baby boomers, with a
      subsequent surge in the elderly population, has led to growing curiosity in the
      geriatric age group with schizophrenia. The nosology of late-onset and very late
      onset schizophrenia like psychosis (VLOSLP) has remained contentious. The
      international late-onset schizophrenia (LOS) group has proposed that
      schizophrenia with an onset between ages 40 and 60 be termed LOS and above 60
      years termed VLOSLP. We present two case reports of VLOSLP and its relevance to
      the present day context. 

PMID- 24860230
TI  - Folie a trois: atypical presentation as shared transient psychotic episode.
AB  - Shared psychotic disorder or induced delusional disorder can occur in different
      clinical settings and profile and is not uncommon. A case of Folie a trois with
      atypical clinical presentation as shared acute transient episode in a bereavement
      setting is reported. Suggestibility, close association and intimacy of the
      affected persons and major stress as psychological trigger act as
      psychopathological factors. 

PMID- 24860231
TI  - A rare case of imitation injury.
AB  - The impact of media on cognitions and behaviors of adolescents is well-known.
      High frequency of exposure to media may distort the reality testing among
      predisposed youth, hence the rise in risk taking behaviors among this population.
      We present a rare manifestation of risk taking behavior in an adolescent who
      injected mercury in his body after exposure to a Hollywood film. The results of
      investigations and possible explanation to understand risk taking behavior in the
      present case are discussed. 

PMID- 24860232
TI  - Should Publications be the Only Means of Assessment? Some Alternatives!

PMID- 24860233
TI  - Clinical potential of allopurinol in the treatment of bipolar disorder.

PMID- 24860234
TI  - Management of prolonged seizures during electroconvulsive therapy.

PMID- 24860235
TI  - A combined experimental and theoretical study of dinitrosyl iron complexes
      containing chelating bis(diphenyl)phosphinoX (X = benzene, propane and ethylene):
      X-ray crystal structures and properties influenced by the presence or absence of
      pi-bonds in chelating ligands.
AB  - Recent discoveries involving the roles of nitric oxide in humans have stimulated
      intense interest in transition metal nitrosyl complexes. A series of dinitrosyl
      iron complexes with the formula [(DPPX)Fe(NO)2], {DPPX = 1,2
      bis(diphenylphosphino)benzene (1), 1,3-bis(diphenylphosphino)propane (2), and cis
      1,2-bis(diphenylphosphino)ethylene (3)} has been prepared and characterized
      through a combination of FT-IR, NMR, UV-vis, X-ray crystallography, and
      electrochemical techniques. Infrared spectroscopy showed NO shifts to the region
      of 1723 and 1674 cm-1 for complexes 1 and 3, and 1708 and 1660 cm-1 for 2,
      indicating that ligand 2 acts as a stronger sigma-donor. The X-ray
      crystallographic data showed that 1 and 3 possess the rare repulso conformation
      while 2 has the attracto conformation. CV studies on compounds 1, 2 and 3 display
      two quasi-reversible oxidations with the E degrees 1/2 values at 0.101 and 0.186
      V, 0.121 and 0.184 V, and 0.019 and 0.342 V, respectively. The larger DeltaE
      value for compound 2 compared with that of 1 and 3 is attributed to the lack of
      pi-bonds between the two phosphorus atoms. Theoretical calculations using density
      functional theory were carried out on the synthesized compounds and model
      compounds and the results are consistent with the experimental data. The
      calculated HOMO-LUMO gaps for compounds 1, 2 and 3 are 3.736, 4.060, and 3.669
      eV, respectively, which supports the stronger back-donation for compound 2 than
      that of compounds 1 and 3.

PMID- 24860236
TI  - A test of multiple hypotheses for the function of call sharing in female
      budgerigars, Melopsittacus undulatus.
AB  - In many social species group, members share acoustically similar calls.
      Functional hypotheses have been proposed for call sharing, but previous studies
      have been limited by an inability to distinguish among these hypotheses. We
      examined the function of vocal sharing in female budgerigars with a two-part
      experimental design that allowed us to distinguish between two functional
      hypotheses. The social association hypothesis proposes that shared calls help
      animals mediate affiliative and aggressive interactions, while the password
      hypothesis proposes that shared calls allow animals to distinguish group identity
      and exclude nonmembers. We also tested the labeling hypothesis, a mechanistic
      explanation which proposes that shared calls are used to address specific
      individuals within the sender-receiver relationship. We tested the social
      association hypothesis by creating four-member flocks of unfamiliar female
      budgerigars (Melopsittacus undulatus) and then monitoring the birds' calls,
      social behaviors, and stress levels via fecal glucocorticoid metabolites. We
      tested the password hypothesis by moving immigrants into established social
      groups. To test the labeling hypothesis, we conducted additional recording
      sessions in which individuals were paired with different group members. The
      social association hypothesis was supported by the development of multiple shared
      call types in each cage and a correlation between the number of shared call types
      and the number of aggressive interactions between pairs of birds. We also found
      support for calls serving as a labeling mechanism using discriminant function
      analysis with a permutation procedure. Our results did not support the password
      hypothesis, as there was no difference in stress or directed behaviors between
      immigrant and control birds.

PMID- 24860237
TI  - Aging without driving: evidence from the Health And Retirement Study, 1993 to
      2008.
AB  - This study characterized older adults who do not drive (former and never drivers)
      and examined how this group of elders has changed over the past 15 years. Sample
      included community-living adults aged 70-85 who do not drive from the 1993 Asset
      and Health Dynamics Among the Oldest Old Study (N = 1,979) and 2008 Health and
      Retirement Study (N = 1,119). Chi-square and t-tests were used to assess
      differences between never and former drivers and between cohorts. Logistic
      regression was used to examine the predictors of having never driven. The driving
      status among older adults has improved over the past 15 years as the proportion
      of never drivers declined from 11% to 2%. However, non-driving has become more
      concentrated among ethnic minority women, and the gaps in education and net worth
      between former and never drivers widened over the 15 years. 

PMID- 24860238
TI  - Schedule Dependence in Cancer Therapy: Intravenous Vitamin C and the Systemic
      Saturation Hypothesis.
AB  - Despite the significant number of in vitro and in vivo studies to assess vitamin
      C effects on cancer following the application of large doses and its extensive
      use by alternative medicine practitioners in the USA; the precise schedule for
      successful cancer therapy is still unknown. Based on interpretation of the
      available data, we postulate that the relationship between Vitamin C doses and
      plasma concentration x time, the capability of tissue stores upon distribution,
      and the saturable mechanism of urinary excretion are all important determinants
      to understand the physiology of high intravenous vitamin C dose administration
      and its effect on cancer. Practitioners should pay more attention to the
      cumulative vitamin C effect instead of the vitamin C concentrations to account
      for observed discrepancy in antitumor response. We suggest that multiple,
      intermittent, short-term intravenous infusions of vitamin C over a longer time
      period will correlate with greater antitumor effects than do single continuous IV
      doses of the same total exposure. This approach would be expected to minimize
      saturation of renal reabsorption, providing a continuous "dynamic flow" of
      vitamin C in the body for optimal systemic exposure and clinical outcomes. This
      prevents the "systemic saturation" phenomena, which may recycle vitamin C and
      render it less effective as an anticancer agent. Nonetheless, more
      pharmacokinetic and pharmacodynamic studies are needed to fully understand this
      schedule-dependence phenomenon.

PMID- 24860239
TI  - A Comparison of Maternal Attachment between American Adolescent and Adult Mothers
      of Preschoolers.
AB  - American adolescent mothers have been viewed as less effective parents than adult
      mothers. The socioeconomic disadvantages of adolescent mothers should be taken
      into account. The objectives of this study were to compare maternal attachment
      between adolescent and adult mothers of preschoolers and to examine changes of
      adolescents' maternal attachment over time. A secondary analysis of data from a
      larger study of maternal employment and low birth weight infant outcomes were
      used. Data were collected through home visits using structured questionnaires at
      two different time points. Forty-three pairs of adolescent and adult mothers who
      could be matched on family structure, maternal race, and child's gestational
      status were compared on maternal attachment. The 7-item Attachment subscale of
      the Parenting Stress Index was used to measure maternal attachment. Results
      revealed that the adolescent mothers were not less attached to their preschoolers
      than the adults. This held true when important confounding factors were taken
      into account using multiple regression.

PMID- 24860240
TI  - Darwin's naturalization hypothesis: scale matters in coastal plant communities.
AB  - Darwin proposed two seemingly contradictory hypotheses for a better understanding
      of biological invasions. Strong relatedness of invaders to native communities as
      an indication of niche overlap could promote naturalization because of
      appropriate niche adaptation, but could also hamper naturalization because of
      negative interactions with native species ('Darwin's naturalization hypothesis').
      Although these hypotheses provide clear and opposing predictions for expected
      patterns of species relatedness in invaded communities, so far no study has been
      able to clearly disentangle the underlying mechanisms. We hypothesize that
      conflicting past results are mainly due to the neglected role of spatial
      resolution of the community sampling. In this study, we corroborate both of
      Darwin's expectations by using phylogenetic relatedness as a measure of niche
      overlap and by testing the effects of sampling resolution in highly invaded
      coastal plant communities. At spatial resolutions fine enough to detect
      signatures of biotic interactions, we find that most invaders are less related to
      their nearest relative in invaded plant communities than expected by chance
      (phylogenetic overdispersion). Yet at coarser spatial resolutions, native
      assemblages become more invasible for closely-related species as a consequence of
      habitat filtering (phylogenetic clustering). Recognition of the importance of the
      spatial resolution at which communities are studied allows apparently contrasting
      theoretical and empirical results to be reconciled. Our study opens new
      perspectives on how to better detect, differentiate and understand the impact of
      negative biotic interactions and habitat filtering on the ability of invaders to
      establish in native communities.

PMID- 24860241
TI  - Rhizospere Redox Cycling and Implications for Rhizosphere Biotransformation of
      Selected Polychlorinated Biphenyl (PCB) Congeners.
AB  - Theoretically, sequential cycles of dechlorination followed by aerobic bio
      oxidation are desirable to achieve complete degradation of a mixture of higher
      and lower chlorinated PCBs. In this research, soil was artificially contaminated
      with polychlorinated biphenyls (PCBs) in mixture and as single congeners, aged,
      and planted with two different plant species. Alternating redox cycles were
      created in the root zone of plants by flooding and draining the soil. Over 32
      weeks, switchgrass (Panicum virgatum) and poplar (Populus deltoids x nigra DN34)
      planted systems that were exposed to alternate cycles of flooding performed
      better in reducing parent PCBs than planted systems that were not cycled
      (p<0.05). The cycled systems also had a higher mass of PCB transformation
      products than the uncycled systems. Multiple cycles were necessary to achieve
      significant differences between the cycled and uncycled treatments.

PMID- 24860242
TI  - Angiogenin reduces immune inflammation via inhibition of TANK-binding kinase 1
      expression in human corneal fibroblast cells.
AB  - Angiogenin (ANG) is reportedly multifunctional, with roles in angiogenesis and
      autoimmune diseases. This protein is involved in the innate immune system and has
      been implicated in several inflammatory diseases. Although ANG may be involved in
      the anti-inflammatory response, there is no evidence that it has direct anti
      inflammatory effects. In this study we sought to determine whether ANG has an
      anti-inflammatory effect in human corneal fibroblasts (HCFs) exposed to media
      containing tumor necrosis factor-alpha (TNF-alpha). We found that ANG reduced the
      mRNA expression of interleukin-1 beta (IL-1beta), -6, -8 and TNF-alpha receptors
      (TNFR) 1 and 2. In contrast, ANG increased the mRNA expression of IL-4 and -10.
      Protein levels of TANK-binding kinase 1 (TBK1) were reduced by ANG in HCFs
      treated with TNF-alpha. Moreover, ANG diminished the expression of IL-6 and -8
      and monocyte chemotactic protein- (MCP-) 1. The protein expression of nuclear
      factor-kappaB (NF-kappaB) was downregulated by ANG treatment. These findings
      suggest that ANG suppressed the TNF-alpha-induced inflammatory response in HCFs
      through inhibition of TBK1-mediated NF-kappaB nuclear translocation. These novel
      results are likely to play a significant role in the selection of immune-mediated
      inflammatory therapeutic targets and may shed light on the pathogenesis of immune
      mediated inflammatory diseases.

PMID- 24860244
TI  - Peak-specific phase correction for automated spectrum processing of in vivo
      magnetic resonance spectroscopic imaging by using the multiscale approach.
AB  - Automatic metabolite quantification with curve fitting is essential in analyzing
      large amount of in vivo magnetic resonance spectroscopic imaging (MRSI) data.
      However, such data analysis is usually hindered by distorted metabolite peaks and
      baselines normally seen in in vivo MRS. In the present study, a multiscale
      approach was utilized for peak-specific automatic phase correction in multi-slice
      MRSI data of human brain. The results suggest that this novel approach can
      improve the robustness and efficiency of metabolite quantification and facilitate
      automatic analysis of multi-slice in vivo MRSI data in human brain.

PMID- 24860243
TI  - Protective effect of astaxanthin on liver fibrosis through modulation of TGF
      beta1 expression and autophagy.
AB  - Liver fibrosis is a common pathway leading to cirrhosis and a worldwide clinical
      issue. Astaxanthin is a red carotenoid pigment with antioxidant, anticancer, and
      anti-inflammatory properties. The aim of this study was to investigate the effect
      of astaxanthin on liver fibrosis and its potential protective mechanisms. Liver
      fibrosis was induced in a mouse model using CCL4 (intraperitoneal injection,
      three times a week for 8 weeks), and astaxanthin was administered everyday at
      three doses (20, 40, and 80 mg/kg). Pathological results indicated that
      astaxanthin significantly improved the pathological lesions of liver fibrosis.
      The levels of alanine aminotransferase aspartate aminotransferase and
      hydroxyproline were also significantly decreased by astaxanthin. The same results
      were confirmed in bile duct liagtion, (BDL) model. In addition, astaxanthin
      inhibited hepatic stellate cells (HSCs) activation and formation of extracellular
      matrix (ECM) by decreasing the expression of NF-kappaB and TGF-beta1 and
      maintaining the balance between MMP2 and TIMP1. In addition, astaxanthin reduced
      energy production in HSCs by downregulating the level of autophagy. These results
      were simultaneously confirmed in vivo and in vitro. In conclusion, our study
      showed that 80 mg/kg astaxanthin had a significant protective effect on liver
      fibrosis by suppressing multiple profibrogenic factors. 

PMID- 24860245
TI  - Improving bone strength prediction in human proximal femur specimens through
      geometrical characterization of trabecular bone microarchitecture and support
      vector regression.
AB  - We investigate the use of different trabecular bone descriptors and advanced
      machine learning tech niques to complement standard bone mineral density (BMD)
      measures derived from dual-energy x-ray absorptiometry (DXA) for improving
      clinical assessment of osteoporotic fracture risk. For this purpose, volumes of
      interest were extracted from the head, neck, and trochanter of 146 ex vivo
      proximal femur specimens on multidetector computer tomography. The trabecular
      bone captured was characterized with (1) statistical moments of the BMD
      distribution, (2) geometrical features derived from the scaling index method
      (SIM), and (3) morphometric parameters, such as bone fraction, trabecular
      thickness, etc. Feature sets comprising DXA BMD and such supplemental features
      were used to predict the failure load (FL) of the specimens, previously
      determined through biomechanical testing, with multiregression and support vector
      regression. Prediction performance was measured by the root mean square error
      (RMSE); correlation with measured FL was evaluated using the coefficient of
      determination R2. The best prediction performance was achieved by a combination
      of DXA BMD and SIM-derived geometric features derived from the femoral head
      (RMSE: 0.869 +/- 0.121, R2: 0.68 +/- 0.079), which was significantly better than
      DXA BMD alone (RMSE: 0.948 +/- 0.119, R2: 0.61 +/- 0.101) (p < 10-4). For
      multivariate feature sets, SVR outperformed multiregression (p < 0.05). These
      results suggest that supplementing standard DXA BMD measurements with
      sophisticated femoral trabecular bone characterization and supervised learning
      techniques can significantly improve biomechanical strength prediction in
      proximal femur specimens.

PMID- 24860246
TI  - MR guided thermal therapy of pancreatic tumors with endoluminal, intraluminal and
      interstitial catheter-based ultrasound devices: Preliminary theoretical and
      experimental investigations.
AB  - Image-guided thermal interventions have been proposed for potential palliative
      and curative treatments of pancreatic tumors. Catheter-based ultrasound devices
      offer the potential for temporal and 3D spatial control of the energy deposition
      profile. The objective of this study was to apply theoretical and experimental
      techniques to investigate the feasibility of endogastric, intraluminal and
      transgastric catheter-based ultrasound for MR guided thermal therapy of
      pancreatic tumors. The transgastric approach involves insertion of a catheter
      based ultrasound applicator (array of 1.5 mm OD x 10 mm transducers, 360 degrees 
      or sectored 180 degrees , ~7 MHz frequency, 13-14G cooling catheter) directly
      into the pancreas, either endoscopically or via image-guided percutaneous
      placement. An intraluminal applicator, of a more flexible but similar construct,
      was considered for endoscopic insertion directly into the pancreatic or biliary
      duct. An endoluminal approach was devised based on an ultrasound transducer
      assembly (tubular, planar, curvilinear) enclosed in a cooling balloon which is
      endoscopically positioned within the stomach or duodenum, adjacent to pancreatic
      targets from within the GI tract. A 3D acoustic bio-thermal model was implemented
      to calculate acoustic energy distributions and used a FEM solver to determine the
      transient temperature and thermal dose profiles in tissue during heating. These
      models were used to determine transducer parameters and delivery strategies and
      to study the feasibility of ablating 1-3 cm diameter tumors located 2-10 mm deep
      in the pancreas, while thermally sparing the stomach wall. Heterogeneous acoustic
      and thermal properties were incorporated, including approximations for tumor
      desmoplasia and dynamic changes during heating. A series of anatomic models based
      on imaging scans of representative patients were used to investigate the three
      approaches. Proof of concept (POC) endogastric and transgastric applicators were
      fabricated and experimentally evaluated in tissue mimicking phantoms, ex vivo
      tissue and in vivo canine model under multi-slice MR thermometry. RF micro-coils
      were evaluated to enable active catheter-tracking and prescription of thermometry
      slice positions. Interstitial and intraluminal ultrasound applicators could be
      used to ablate (t43>240 min) tumors measuring 2.3-3.4 cm in diameter when powered
      with 20-30 W/cm2 at 7 MHz for 5-10 min. Endoluminal applicators with planar and
      curvilinear transducers operating at 3-4 MHz could be used to treat tumors up to
      20-25 mm deep from the stomach wall within 5 min. POC devices were fabricated and
      successfully integrated into the MRI environment with catheter tracking, real
      time thermometry and closed-loop feedback control.

PMID- 24860247
TI  - Working with families in which a parent has depression: A resilience perspective.
AB  - The association between parental depression and child maladjustment is well
      documented in the literature. Less is known about the strengths and potential
      protective mechanisms that help promote resilience for this population. This
      literature review on resilience in these families was conducted to help inform
      policy and practice for these families. Five protective factors (goodness of fit,
      self-esteem and self-efficacy, social support, family functioning, and
      opportunities for change) and four practice principles (discovery of resources
      and abilities, explanation of risk and protective factors, development of both
      collaborative family relationships, and social support) emerged from this review.
      Implications for policy and practice in light of these principles are provided.

PMID- 24860248
TI  - A Universal Electrode Approach for Automated Electrochemical Molecular Analyses.
AB  - Transforming microfluidics-based biosensing systems from laboratory research into
      clinical reality remains an elusive goal despite decades of intensive research. A
      fundamental obstacle for the development of fully automated microfluidic
      diagnostic systems is the lack of an effective strategy for combining pumping,
      sample preparation, and detection modules into an integrated biosensing platform.
      Herein, we report a universal electrode approach, which incorporates DC
      electrolytic pumping, AC electrokinetic sample preparation, and self-assembled
      monolayer based electrochemical sensing on a single microfluidic platform, to
      automate complicated molecular analysis procedures that will enable biosensing
      applications in non-traditional healthcare settings. Using the universal
      electrode approach, major microfluidic operations required in molecular analyses,
      such as pumping, mixing, washing, and sensing can be performed in a single
      platform. We demonstrate the universal electrode platform for detecting bacterial
      16S rRNA, a phylogenetic marker, toward rapid diagnostics of urinary tract
      infection. Since only electronic interfaces are required to operate the platform,
      the universal electrode approach represents an effective system integration
      strategy to realize the potential of microfluidics in molecular diagnostics at
      the point of care.

PMID- 24860249
TI  - The Social Contexts of Drug Offers and Their Relationship to Drug Use of Rural
      Hawaiian Youth.
AB  - This paper examines the differences in drug offers and recent drug use between
      Hawaiian and non-Hawaiian youth residing in rural communities, and the
      relationship between drug offers and drug use of Hawaiian youth in these
      communities. Two hundred forty nine youth (194 Hawaiian youth) from 7 different
      middle or intermediate schools completed a survey focused on the social context
      of drug offers. Hawaiian youth in the study received significantly more offers
      from peers and family, and had significantly higher rates of recent alcohol and
      marijuana use, compared with non-Hawaiian youth. Logistic regression analysis
      indicated that the social context differentially influenced drug use of Hawaiian
      youth, with family drug offers and context influencing overall drug use and the
      use of the widest variety of substances. Implications for prevention practices
      are discussed.

PMID- 24860250
TI  - Optimizing medication adherence communication with prescribers.

PMID- 24860251
TI  - Evaluating a moving target: Using Practical Participatory Evaluation (P-PE) in
      hospital settings.
AB  - This article describes lessons learned about implementing evaluations in hospital
      settings. In order to overcome the methodological dilemmas inherent in this
      environment, we used a practical participatory evaluation strategy to engage as
      many stakeholders as possible in the process of evaluating a clinical
      demonstration project. Demonstration projects, in this context, push the envelope
      about what is known about effectiveness in novel settings, and turnover of staff
      and patient populations can present challenges to gathering optimal data. By
      using P-PE, we built capacity in the environment while expanding possibilities
      for data collection. Suggestions are made based on our experience.

PMID- 24860252
TI  - Ultrasound-guided transversus abdominis plane blocks for patients undergoing
      laparoscopic hand-assisted nephrectomy: a randomized, placebo-controlled trial.
AB  - Postoperative pain is a common complaint following living kidney donation or
      tumor resection using the laparoscopic hand-assisted technique. To evaluate the
      potential analgesic benefit of transversus abdominis plane blocks, we conducted a
      randomized, double-blind, placebo-controlled study in 21 patients scheduled to
      undergo elective living-donor nephrectomy or single-sided nephrectomy for tumor.
      Patients were randomized to receive either 20 mL of 0.5% ropivacaine or 20 mL of
      0.9% saline bilaterally to the transversus abdominis plane under ultrasound
      guidance. We found that transversus abdominis plane blocks reduced overall pain
      scores at 24 hours, with a trend toward decreased total morphine consumption.
      Nausea, vomiting, sedation, and time to discharge were not significantly
      different between the two study groups. 

PMID- 24860253
TI  - Predicting Intra-Urban Variation in Air Pollution Concentrations with Complex
      Spatio-Temporal Dependencies.
AB  - We describe a methodology for assigning individual estimates of long-term average
      air pollution concentrations that accounts for a complex spatio-temporal
      correlation structure and can accommodate spatio-temporally misaligned
      observations. This methodology has been developed as part of the Multi-Ethnic
      Study of Atherosclerosis and Air Pollution (MESA Air), a prospective cohort study
      funded by the U.S. EPA to investigate the relationship between chronic exposure
      to air pollution and cardiovascular disease. Our hierarchical model decomposes
      the space-time field into a "mean" that includes dependence on covariates and
      spatially varying seasonal and long-term trends and a "residual" that accounts
      for spatially correlated deviations from the mean model. The model accommodates
      complex spatio-temporal patterns by characterizing the temporal trend at each
      location as a linear combination of empirically derived temporal basis functions,
      and embedding the spatial fields of coefficients for the basis functions in
      separate linear regression models with spatially correlated residuals (universal
      kriging). This approach allows us to implement a scalable single-stage estimation
      procedure that easily accommodates a significant number of missing observations
      at some monitoring locations. We apply the model to predict long-term average
      concentrations of oxides of nitrogen (NOx) from 2005-2007 in the Los Angeles
      area, based on data from 18 EPA Air Quality System regulatory monitors. The cross
      validated R2 is 0.67. The MESA Air study is also collecting additional
      concentration data as part of a supplementary monitoring campaign. We describe
      the sampling plan and demonstrate in a simulation study that the additional data
      will contribute to improved predictions of long-term average concentrations.

PMID- 24860254
TI  - Ny-1 and Ny-2 genes conferring hypersensitive response to potato virus Y (PVY) in
      cultivated potatoes: mapping and marker-assisted selection validation for PVY
      resistance in potato breeding.
AB  - Potato virus Y (PVY) is one of the most important viruses affecting potato
      (Solanum tuberosum) production. In this study, a novel hypersensitive response
      (HR) gene, Ny-2, conferring resistance to PVY was mapped on potato chromosome XI
      in cultivar Romula. In cultivars Albatros and Sekwana, the Ny-1 gene was mapped
      on chromosome IX. In cv. Romula, the local lesions appeared in leaves inoculated
      with the PVYN-Wi isolate at 20 and 28  degrees C; PVY systemic infections were
      only occasionally observed at the higher temperature. In cvs. Albatros and
      Sekwana, expression of the necrotic reaction to virus infection was temperature
      dependent. PVYN-Wi was localized at 20  degrees C; at 28  degrees C, the
      systemic, symptomless infection was observed. We developed the B11.61600 marker
      co-segregating with Ny-2 and the S1d11 marker specific for the Ny-1 gene. Fifty
      potato cultivars were tested with markers B11.6 and S1d11 and marker SC895 linked
      to the Ny-1 gene in cv. Rywal. These results indicated the utility of these
      markers for marker-assisted selection of HR-like PVY resistance in potato
      breeding programs.

PMID- 24860255
TI  - Micro-bias and macro-performance.
AB  - We use agent-based modeling to investigate the effect of conservatism and
      partisanship on the efficiency with which large populations solve the density
      classification task - a paradigmatic problem for information aggregation and
      consensus building. We find that conservative agents enhance the populations'
      ability to efficiently solve the density classification task despite large levels
      of noise in the system. In contrast, we find that the presence of even a small
      fraction of partisans holding the minority position will result in deadlock or a
      consensus on an incorrect answer. Our results provide a possible explanation for
      the emergence of conservatism and suggest that even low levels of partisanship
      can lead to significant social costs.

PMID- 24860257
TI  - Ki-67 is a strong prognostic marker of non-small cell lung cancer when tissue
      heterogeneity is considered.
AB  - BACKGROUND: Ki-67 expression is a well-established prognostic marker in various
      cancers. However, Ki-67 expression is also known as being heterogeneous. We
      investigated the prognostic significance of Ki-67 from the view of staining
      heterogeneity by the technique of Spiral Array. METHODS: 100 cases of resected
      lung cancer from Toyama university hospital archive were collected. Spiral Array
      blocks were generated out of 100 cases using 100 MUm thick paraffin sections.
      Four MUm thick sections of the Array block were stained for Ki-67. Staining
      results in each reel were scored for areas with lowest (LS), highest (HS), and
      average (AS) expression, exclusively in the cancer cells. Heterogeneity score
      (HeS) was designed as the difference between HS and LS. The scores were divided
      into four grades (0-3). Clinical information was collected, and the prognostic
      significance of Ki-67 was analyzed. RESULTS: Pathological stage was available for
      91 patients (43 stage IA, 22 stage IB, 2 stage IIA, 9 stage IIB, 13 stage IIIA, 1
      stage IIIB, and 1 stage IV). The HS of Ki-67 score in non-small cell lung cancer
      was 3 in 17 cases, 2 in 27 cases, 1 in 28 cases, 0 in 21 cases, and 4 reels were
      lost. 78 cases had clinical follow up. 74 cases had all the information available
      and were analyzed for correlation between Ki-67 expression and survival. Cases
      with score 2 and 3 of HS and HeS showed significant poorer prognosis (both P <
      0.001), whereas LS or AS did not show significance. The results were identical
      when analyzing adenocarcinoma and squamous cell carcinoma, separately. Cox
      multivariate analysis of Ki-67 showed that HS was an independent risk factor
      affecting overall survival. CONCLUSIONS: Ki-67 is a strong prognostic marker for
      non-small cell lung cancer when the degree of highest staining frequency or
      heterogeneity is considered.

PMID- 24860256
TI  - Intubating conditions and side effects of propofol, remifentanil and sevoflurane
      compared with propofol, remifentanil and rocuronium: a randomised, prospective,
      clinical trial.
AB  - BACKGROUND: Tracheal intubation without muscle relaxants is usually performed
      with remifentanil and propofol or sevoflurane. Remifentanil 1.0 to 4.0 MUg.kg(-1)
      and propofol 2.0-3.0 mg.kg(-1) or sevoflurane up to 8.0 Vol% provide acceptable,
      i.e. excellent or good intubating conditions. We hypothesized that sevoflurane
      1.0 MAC would provide acceptable intubating conditions when combined with
      propofol and remifentanil. METHODS: Eighty-three patients to be intubated were
      randomised to two groups. The SEVO group received propofol 1.5 mg kg(-1),
      remifentanil 0.30 MUg kg min(-1) and sevoflurane 1.0 MAC; the MR group received
      the same doses of propofol and remifentanil plus rocuronium 0.45 mg kg(-1). We
      evaluated intubation and extubation conditions, mean arterial pressure (MAP),
      heart rate (HR) and bispectral index (BIS). The vocal cords were examined for
      injury by videolaryngoscopy before and 24 hours after surgery. RESULTS:
      ACCEPTABLE INTUBATING CONDITIONS WERE SEEN MORE FREQUENTLY WITH ROCURONIUM THAN
      WITH SEVOFLURANE: 97% versus 82%; p = 0.03; the subscore for vocal cords was
      comparable: 100% versus 98%. MAP before intubation decreased significantly
      compared with the MAP at baseline to the same extent in both groups; ephedrine IV
      was given in 15 (SEVO) versus 16 (MR) patients; p = 0.93. BIS at tracheal
      intubation was 27 (13-65) in the SEVO group, 29 (14-62) in the MR group; p =
      0.07. Vocal cord injuries (oedema, haematoma) were similar: 4 patients in each
      group. CONCLUSIONS: Overall intubating conditions were better when rocuronium was
      used; the subscore for vocal cords was comparable. The incidence of side effects
      was the same in the two groups. TRIAL REGISTRATION: ClinicalTrials.Gov: NCT
      01591031.

PMID- 24860258
TI  - Glutamate involvement in calcium-dependent migration of astrocytoma cells.
AB  - BACKGROUND: Astrocytoma are known to have altered glutamate machinery that
      results in the release of large amounts of glutamate into the extracellular space
      but the precise role of glutamate in favoring cancer processes has not yet been
      fully established. Several studies suggested that glutamate might provoke active
      killing of neurons thereby producing space for cancer cells to proliferate and
      migrate. Previously, we observed that calcium promotes disassembly of integrin
      containing focal adhesions in astrocytoma, thus providing a link between calcium
      signaling and cell migration. The aim of this study was to determine how calcium
      signaling and glutamate transmission cooperate to promote enhanced astrocytoma
      migration. METHODS: The wound-healing model was used to assay migration of human
      U87MG astrocytoma cells and allowed to monitor calcium signaling during the
      migration process. The effect of glutamate on calcium signaling was evaluated
      together with the amount of glutamate released by astrocytoma during cell
      migration. RESULTS: We observed that glutamate stimulates motility in serum
      starved cells, whereas in the presence of serum, inhibitors of glutamate
      receptors reduce migration. Migration speed was also reduced in presence of an
      intracellular calcium chelator. During migration, cells displayed spontaneous
      Ca(2+) transients. L-THA, an inhibitor of glutamate re-uptake increased the
      frequency of Ca(2+) oscillations in oscillating cells and induced Ca(2+)
      oscillations in quiescent cells. The frequency of migration-associated Ca(2+)
      oscillations was reduced by prior incubation with glutamate receptor antagonists
      or with an anti-beta1 integrin antibody. Application of glutamate induced
      increases in internal free Ca(2+) concentration ([Ca(2+)]i). Finally we found
      that compounds known to increase [Ca(2+)]i in astrocytomas such as thapsigagin,
      ionomycin or the metabotropic glutamate receptor agonist t-ACPD, are able to
      induce glutamate release. CONCLUSION: Our data demonstrate that glutamate
      increases migration speed in astrocytoma cells via enhancement of migration
      associated Ca(2+) oscillations that in turn induce glutamate secretion via an
      autocrine mechanism. Thus, glutamate receptors are further validated as potential
      targets for astrocytoma cancer therapy.

PMID- 24860259
TI  - Mentors and tormentors on the road to informatics.

PMID- 24860260
TI  - A characterization of clinical questions asked by rehabilitation therapists.
AB  - OBJECTIVE: This study explored the information needs of rehabilitation therapists
      (occupational therapists, physical therapists, and speech-language pathologists)
      working with patients who have had strokes in order to characterize their
      clinical questions, defined as their formalized information needs arising in the
      context of everyday clinical practice. METHODS: The researchers took a
      constructivist, interpretive approach, in which fifteen rehabilitation therapists
      working in various settings were recruited. Data were gathered using diaries,
      followed by diary-guided interviews, and thematically analyzed using template
      analysis. RESULTS: Rehabilitation therapists' clinical questions were
      characterized as having one or more of twelve foci and containing one or more of
      eight possible structural elements. CONCLUSIONS: Findings demonstrate that the
      evidence-based practice framework currently applied for questions relating to
      rehabilitation is inadequate for representing rehabilitation therapists' clinical
      questions. A new framework that is more comprehensive and descriptive is
      proposed. IMPLICATIONS: Librarians working with students and clinicians in
      rehabilitation can employ knowledge of the twelve foci and the question structure
      for rehabilitation to guide the reference interview. Instruction on question
      formulation in evidence-based practice can employ the revised structure for
      rehabilitation, offering students and clinicians an alternative to the
      traditional patient, intervention, comparison, outcome (PICO) structure.
      Information products, including bibliographic databases and synopsis services,
      can tailor their interfaces according to question foci and prompt users to enter
      search terms corresponding to any of the eight possible elements found in
      rehabilitation therapists' clinical questions.

PMID- 24860261
TI  - What criteria do consumer health librarians use to develop library collections? a
      phenomenological study.
AB  - OBJECTIVES: The criteria for determining whether resources are included in
      consumer health library collections are summarized in institutional collection
      development policies (CDPs). Evidence suggests that CDPs do not adequately
      capture all of these criteria. The aim of this study was to describe the resource
      review experience of librarians and compare it to what is described in CDPs.
      METHODS: A phenomenological approach was used to explore and describe the
      process. Four consumer health librarians independently evaluated cancer-related
      consumer health resources and described their review process during a semi
      structured telephone interview. Afterward, these librarians completed online
      questionnaires about their approaches to collection development. CDPs from
      participating libraries, interview transcripts, and questionnaire data were
      analyzed. Researchers summarized the findings, and participating librarians
      reviewed results for validation. RESULTS: Librarians all utilized similar
      criteria, as documented in their CDPs; however, of thirteen criteria described in
      the study, only four were documented in CDPs. CONCLUSIONS: CDPs for consumer
      health libraries may be missing important criteria that are considered integral
      parts of the collection development process. IMPLICATIONS: A better understanding
      of the criteria and contextual factors involved in the collection development
      process can assist with establishing high-quality consumer health library
      collections.

PMID- 24860262
TI  - Introduction: highlighting international librarianship.

PMID- 24860263
TI  - The ethics of scholarly publishing: exploring differences in plagiarism and
      duplicate publication across nations.
AB  - This study explored national differences in plagiarism and duplicate publication
      in retracted biomedical literature. The national affiliations of authors and
      reasons for retraction of papers accessible through PubMed that were published
      from 2008 to 2012 and subsequently retracted were determined in order to identify
      countries with the largest numbers and highest rates of retraction due to
      plagiarism and duplicate publication. Authors from more than fifty countries
      retracted papers. While the United States retracted the most papers, China
      retracted the most papers for plagiarism and duplicate publication. Rates of
      plagiarism and duplicate publication were highest in Italy and Finland,
      respectively. Unethical publishing practices cut across nations. 

PMID- 24860265
TI  - Improving medical education in Kenya: an international collaboration.
AB  - This paper describes a partnership between the University of Nairobi College of
      Health Sciences (CHS) Library and the University of Maryland Health Sciences and
      Human Services Library (HS/HSL). The libraries are collaborating to develop best
      practices for the CHS Library as it meets the challenge of changing medical
      education information needs in a digital environment. The collaboration is part
      of a Medical Education Partnership Initiative. The library project has several
      components: an assessment of the CHS Library, learning visits in the United
      States and Kenya, development of recommendations to enhance the CHS Library, and
      ongoing evaluation of the program's progress. Development of new services and
      expertise at the CHS Library is critical to the project's success. A productive
      collaboration between the HS/HSL and CHS Library is ongoing. A successful program
      to improve the quality of medical education will have a beneficial impact on
      health outcomes in Kenya. 

PMID- 24860264
TI  - Building capacity in a health sciences library to support global health projects.
AB  - This paper describes how a large, academic health sciences library built capacity
      for supporting global health at its university and discusses related outcomes.
      Lean budgets require prioritization and organizational strategy. A committee,
      with leadership responsibilities assigned to one librarian, guided strategic
      planning and the pursuit of collaborative, global health outreach activities. A
      website features case studies and videos of user stories to promote how library
      partnerships successfully contributed to global health projects. Collaborative
      partnerships were formed through outreach activities and from follow-up to
      reference questions. The committee and a librarian's dedicated time established
      the library's commitment to help the university carry out its ambitious global
      agenda. 

PMID- 24860266
TI  - Information empowerment: predeparture resource training for students in global
      health.
AB  - The Taubman Health Sciences Library (THL) collaborates with health sciences
      schools to provide information skills instruction for students preparing for
      international experiences. THL enhances students' global health learning through
      predeparture instruction for students who are involved in global health research,
      clinical internships, and international collaborations. This includes teaching
      international literature searching skills, providing country-specific data
      sources, building awareness of relevant mobile resources, and encouraging
      investigation of international news. Information skills empower creation of
      stronger global partnerships. Use of information resources has enhanced
      international research and training experiences, built lifelong learning
      foundations, and contributed to the university's global engagement. THL continues
      to assess predeparture instruction. 

PMID- 24860267
TI  - Developing an evidence-based list of journals for nursing.
AB  - The Nursing and Allied Health Resources Section (NAHRS) of the Medical Library
      Association created the 2012 NAHRS Selected List of Nursing Journals to assist
      librarians with collection development and to provide nurses and librarians with
      data on nursing and interdisciplinary journals to assist their decisions about
      where to submit articles for publication. This list is a continuation and
      expansion of a list initially known as the Key Nursing Journals list. It compares
      database coverage and full-text options for each title and includes an analysis
      of the number of evidence-based, research, and continuing education articles. 

PMID- 24860268
TI  - Pharmacy journal abstracts published in PubMed that abide by the CONsolidated
      Standards Of Reporting Trials (CONSORT) guidelines.
AB  - The purpose of this research was to determine the proportion of abstracts in
      pharmacy journals that are prepared according to the CONsolidated Standards Of
      Reporting Trials (CONSORT) criteria for abstracts. Certain abstracts for
      randomized controlled clinical trials (RCTs) indexed in PubMed were eligible for
      inclusion, with the primary endpoint being median overall compliance to CONSORT
      recommendations for abstracts. A total of 63 RCT abstracts were included in the
      analysis, with only 56% of the recommended CONSORT items represented in the
      sample. It is recommended that pharmacy journals encourage authors to follow
      CONSORT recommendations for abstracts when submitting RCTs for publication. 

PMID- 24860269
TI  - Copyright information queries in the health sciences: trends and implications
      from the Ohio State University.
AB  - OBJECTIVE: This paper presents the results of data gathered on copyright
      questions asked at an academic health sciences library. METHODS: Collected data
      include questioner's status or discipline, the subject of the questions, the
      types of activities that the questioners were engaged in, the communication mode,
      and the length of time it took to answer the questions. RESULTS: Overall results
      showed most questions were about permissions. Staff asked the most questions,
      followed by faculty and students. CONCLUSIONS: Copyright education is needed at
      universities, and further analysis of queries will determine the direction of the
      education.

PMID- 24860270
TI  - Assessment of drug information resource preferences of pharmacy students and
      faculty.
AB  - A 39-item survey instrument was distributed to faculty and students at Wingate
      University School of Pharmacy to assess student and faculty drug information (DI)
      resource use and access preferences. The response rate was 81% (n = 289). Faculty
      and professional year 2 to 4 students preferred access on laptop or desktop
      computers (67% and 75%, respectively), followed by smartphones (27% and 22%,
      respectively). Most faculty and students preferred using Lexicomp Online for drug
      information (53% and 74%, respectively). Results indicate that DI resources use
      is similar between students and faculty; laptop or desktop computers are the
      preferred platforms for accessing drug information. 

PMID- 24860271
TI  - A global snapshot of the state of digital collections in the health sciences,
      2013.
AB  - Two hundred twenty-nine health sciences libraries (HSLs) worldwide were surveyed
      regarding the availability of digital collections, evidence of the type of
      digital collections, level of access, software used, and HSL type. Of the
      surveyed libraries, 69% (n = 157) had digital collections, with an average of
      1,531 items in each collection; 49% (n = 112) also had institutional
      repositories. In most cases (n = 147), these collections were publicly available.
      The predominant platforms for disseminating these digital collections were
      CONTENTdm and library web pages. Only 50% (n = 77) of these collections were
      managed by the health sciences library itself. 

PMID- 24860272
TI  - Measuring patrons' technology habits: an evidence-based approach to tailoring
      library services.
AB  - Librarians continually integrate new technologies into library services for
      health sciences students. Recently published data are lacking about student
      ownership of technological devices, awareness of new technologies, and interest
      in using devices and technologies to interact with the library. A survey was
      implemented at seven health sciences libraries to help answer these questions.
      Results show that librarian assumptions about awareness of technologies are not
      supported, and student interest in using new technologies to interact with the
      library varies widely. Collecting this evidence provides useful information for
      successfully integrating technologies into library services. 

PMID- 24860274
TI  - Supervisor Training Makes a Difference with a Tough Issue.

PMID- 24860275
TI  - How Accurate Are Transition States from Simulations of Enzymatic Reactions?
AB  - The rate expression of traditional transition state theory (TST) assumes no
      recrossing of the transition state (TS) and thermal quasi-equilibrium between the
      ground state and the TS. Currently, it is not well understood to what extent
      these assumptions influence the nature of the activated complex obtained in
      traditional TST-based simulations of processes in the condensed phase in general
      and in enzymes in particular. Here we scrutinize these assumptions by
      characterizing the TSs for hydride transfer catalyzed by the enzyme Escherichia
      coli dihydrofolate reductase obtained using various simulation approaches.
      Specifically, we compare the TSs obtained with common TST-based methods and a
      dynamics-based method. Using a recently developed accurate hybrid quantum
      mechanics/molecular mechanics potential, we find that the TST-based and dynamics
      based methods give considerably different TS ensembles. This discrepancy, which
      could be due equilibrium solvation effects and the nature of the reaction
      coordinate employed and its motion, raises major questions about how to interpret
      the TSs determined by common simulation methods. We conclude that further
      investigation is needed to characterize the impact of various TST assumptions on
      the TS phase-space ensemble and on the reaction kinetics.

PMID- 24860276
TI  - Revisiting H2O Nucleation around Au+ and Hg2+: The Peculiar "Pseudo-Soft"
      Character of the Gold Cation.
AB  - In this contribution, we propose a deeper understanding of the electronic effects
      affecting the nucleation of water around the Au+ and Hg2+ metal cations using
      quantum chemistry. To do so, and in order to go beyond usual energetical studies,
      we make extensive use of state of the art quantum interpretative techniques
      combining ELF/NCI/QTAIM/EDA computations to capture all ranges of interactions
      stabilizing the well characterized microhydrated structures. The Electron
      Localization Function (ELF) topological analysis reveals the peculiar role of the
      Au+ outer-shell core electrons (subvalence) that appear already spatially
      preorganized once the addition of the first water molecule occurs. Thus, despite
      the addition of other water molecules, the electronic structure of Au(H2O)+
      appears frozen due to relativistic effects leading to a maximal acceptation of
      only two waters in gold's first hydration shell. As the values of the QTAIM
      (Quantum Theory of Atoms in Molecules) cations's charge is discussed, the Non
      Covalent Interactions (NCI) analysis showed that Au+ appears still able to
      interact through longer range van der Waals interaction with the third or fourth
      hydration shell water molecules. As these types of interaction are not
      characteristic of either a hard or soft metal cation, we introduced the concept
      of a "pseudo-soft" cation to define Au+ behavior. Then, extending the study, we
      performed the same computations replacing Au+ with Hg2+, an isoelectronic cation.
      If Hg2+ behaves like Au+ for small water clusters, a topological, geometrical,
      and energetical transition appears when the number of water molecules increases.
      Regarding the HSAB theory, this transition is characteristic of a shift of Hg2+
      from a pseudosoft form to a soft ion and appears to be due to a competition
      between the relativistic and correlation effects. Indeed, if relativistic effects
      are predominant, then mercury will behave like gold and have a similar
      subvalence/geometry; otherwise when correlation effects are predominant, Hg2+
      behaves like a soft cation.

PMID- 24860278
TI  - One-photon scattering by an atomic chain in a two-mode resonator: cyclic
      conditions.
AB  - In this work, a chain of N identical two-level atoms coupled with a quantized
      electromagnetic field, initially prepared via a single-photon Fock state, is
      investigated. The N-particle state amplitude of the system is calculated for
      several space configurations of the atoms in the Weisskopf-Wigner approximation.
      It was shown that the space configuration of an atomic chain, the total number of
      atoms, and even the available volume for the field modes define the behavior of
      the system state amplitude with time. Applying the condition of 'cyclic bonds',
      presented in this work, to the elaborated theory allows to describe the system
      time evolution, practically, for any space configuration. 

PMID- 24860277
TI  - The effect of almond consumption on elements of endurance exercise performance in
      trained athletes.
AB  - BACKGROUND: Almonds are a healthy tree nut food with high nutrient density. Their
      consumption has been shown to ameliorate oxidative stress, inflammation, etc. The
      objective of the study was to examine the effect of almonds on elements of
      endurance exercise performance in trained athletes. METHODS: A 10-week crossover,
      placebo controlled study was conducted. Eight trained male cyclists and two
      triathletes were randomly assigned to consume 75 g/d whole almonds (ALM) or
      isocaloric cookies (COK) with equal subject number. They consumed the assigned
      food for 4 wks and then the alternate food for another 4 wks. They underwent 3
      performance tests including 125-min steady status exercise (SS) and 20-min time
      trial (TT) on an indoor stationary trainer at the start of the study (BL) and at
      the end of each intervention phase. Venous blood was collected in the morning
      prior to the performance test for biochemical measurements and finger blood
      during the test for glucose determination. Carbohydrate and fat oxidation, energy
      expenditure, and oxygen use were calculated using respiratory gas analysis.
      RESULTS: ALM increased cycling distance during TT by 1.7 km as compared BL (21.9
      vs. 20.2 km, P = 0.053) and COK increased 0.6 km (20.8 vs. 20.2 km, P > 0.05).
      ALM, but not COK, led to higher CHO and lower fat oxidation and less oxygen
      consumption during TT than BL (P < 0.05), whereas there was no significant
      difference in heart rate among BL, ALM and COK. ALM maintained higher blood
      glucose level after TT than COK (P < 0.05). ALM had higher vitamin E and
      haemoglobin and lower serum free fatty acid (P < 0.05), slightly elevated serum
      arginine and nitric oxide and plasma insulin (P > 0.05) than BL, and a higher
      total antioxidant capacity than COK (P < 0.05). CONCLUSIONS: Whole almonds
      improved cycling distance and the elements related to endurance performance more
      than isocaloric cookies in trained athletes as some nutrients in almonds may
      contribute to CHO reservation and utilization and effective oxygen utilization.
      The results suggest that almonds can be incorporated into diets of those who
      undertake exercise training for performance improvement.

PMID- 24860279
TI  - Decadal Cycles in the Human Cardiovascular System.
AB  - Seven of the eight authors of this report each performed physiologic self
      surveillance, some around the clock for decades. We here document the presence of
      long cycles (decadals, including circaundecennians) in the time structure of
      systolic (S) and diastolic (D) blood pressure (BP) and heart rate (HR). Because
      of the non-stationary nature in time and space of these and other physiologic and
      environmental periodic components that, like the wind, can appear and disappear
      in a given or other geographic location at one or another time, they have been
      called "Aeolian". The nonlinear estimation of the uncertainties of the periods
      (taus) of two or more variables being compared has been used to determine whether
      these components are congruent or not, depending on whether their CIs (95%
      confidence intervals) overlap or not. Among others, congruence has been found for
      components with taus clustering around 10 years in us and around us. There is a
      selective assortment among individuals, variables and cycle characteristics (mean
      and circadian amplitude and acrophase). Apart from basic interest, like other
      nonphotic solar signatures such as transyears with periods slightly longer than
      one year or about 33-year Bruckner-Egeson-Lockyer (BEL) cycles, about 10-year and
      longer cycles present in 7 of 7 self-monitoring individuals are of interest in
      the diagnosis of Vascular Variability Anomalies (VVAs), including MESOR
      hypertension, and others. Some of the other VVAs, such as a circadian overswing,
      i.e., CHAT (Circadian Hyper-Aplitude-Tension), or an excessive pulse pressure,
      based on repeated 7-day around-the-clock records, can represent a risk of severe
      cardiovascular events, greater than that of a high BP. The differential diagnosis
      of physiologic cycles, infradians (components with a tau longer than 28 hours) as
      well as circadians awaits the collection of reference values for the infradian
      parameters of the cycles described herein. Just as in stroke-prone spontaneously
      hypertensive rats during the weeks after weaning CHAT precedes an elevation of
      the BP MESOR, a decadal overswing seems to precede the occurrence of high BP in
      two of the subjects here examined. Only around-the-clock monitoring in health for
      the collection of reference values will allow on their basis the differential
      diagnosis of the onsets of a circadian versus a circadecadal overswing in BP and
      the specification whether, and if so, when to initiate hypotensive non-drug or
      drug treatment.

PMID- 24860280
TI  - Biosynthesis and Antimicrobial Activity of Semiconductor Nanoparticles against
      Oral Pathogens.
AB  - Dental care is an essential phenomenon in human health. Oral pathogens can cause
      severe break which may show the way to serious issues in human disease like blood
      circulation and coronary disease. In the current study, we demonstrated the
      synthesis and antimicrobial activity of cadmium sulphide and zinc sulphide
      nanoparticles against oral pathogens. The process for the synthesis of cadmium
      sulphide (CdS) and zinc sulphide (ZnS) nanoparticles is fast, novel, and
      ecofriendly. Formation of cadmium sulphide (CdS) and zinc sulphide (ZnS)
      nanoparticles was confirmed by surface plasmon spectra using UV-Vis
      spectrophotometer. The morphology of crystalline phase of nanoparticles was
      determined from transmission electron microscopy (TEM) and X-ray diffraction
      (XRD) spectra. The average size of cadmium sulphide (CdS) and zinc sulphide (ZnS)
      nanoparticles was in the range of 10 nm to 25 nm and 65 nm, respectively, and the
      observed morphology was spherical. The results indicated that the proteins, which
      contain amine groups, played a reducing and controlling responsibility during the
      formation of cadmium sulphide (CdS) and zinc sulphide (ZnS) nanoparticles in the
      colloidal solution. The antimicrobial activity was assessed against oral
      pathogens such as Streptococcus sp. Staphylococcus sp. Lactobacillus sp., and
      Candida albicans and these results confirmed that the sulphide nanoparticles are
      exhibiting good bactericidal activity. 

PMID- 24860281
TI  - Lactobacillus salivarius and L. gasseri down-regulate Aggregatibacter
      actinomycetemcomitans exotoxins expression.
AB  - Beneficial microbes, such as lactobacilli establish a symbiosis with the host and
      confer health-associated effects, by limiting the growth of indigenous pathogens
      and challenging microbes introduced by altered foods. Nevertheless, there is
      scarce information on the effects of beneficial microbes on the virulence
      properties of bacterial species associated with oral diseases, such as
      periodontitis. Aggregatibacter actinomycetemcomitans is a Gram-negative species
      highly implicated in the etiology of localized aggressive periodontitis. The
      objective of this study was to investigate the effect of lactobacilli on the
      expression of the two major virulence factors of A. actinomycetemcomitans.
      Lactobacillus salivarius and L. gasseri were selected as beneficial species. The
      gene expressions of leukotoxin (LtxA) and cytolethal distending toxin (CdtB) by
      A. actinomycetemcomitans were analyzed in response to challenge by lactobacilli
      cell-free supernatants. Neither lactobacilli affected the growth, but strongly
      attenuated the expressions of both CdtB and LtxA in the two A.
      actinomycetemcomitans strains tested. This reduction of the expression of these
      two exotoxins was time-dependent. These fundamental findings may indicate that
      lactobacilli can reduce the virulence of putative opportunistic oral pathogens,
      and may provide insights to future therapeutic approaches for the respective
      diseases.

PMID- 24860282
TI  - Metagenomic analyses reveal phylogenetic diversity of carboxypeptidase gene
      sequences in activated sludge of a wastewater treatment plant in Shanghai, China.
AB  - Activated sludge of wastewater treatment plants carries a diverse microflora.
      However, up to 80-90 % of microorganisms in activated sludge cannot be cultured
      by current laboratory techniques, leaving an enzyme reservoir largely unexplored.
      In this study, we investigated carboxypeptidase diversity in activated sludge of
      a wastewater treatment plant in Shanghai, China, by a culture-independent
      metagenomic approach. Three sets of consensus degenerate hybrid oligonucleotide
      primers (CODEHOPs) targeting conserved domains of public carboxypeptidases have
      been designed to amplify carboxypeptidase gene sequences in the metagenomic DNA
      of activated sludge by PCR. The desired amplicons were evaluated by
      carboxypeptidase sequence clone libraries and phylogenetic analyses. We uncovered
      a significant diversity of carboxypeptidases present in the activated sludge.
      Deduced carboxypeptidase amino acid sequences (127-208 amino acids) were
      classified into three distinct clusters, alpha, beta, and gamma. Sequences
      belonging to clusters alpha and beta shared 58-97 % identity to known
      carboxypeptidase sequences from diverse species, whereas sequences in the cluster
      gamma were remarkably less related to public carboxypeptidase homologous in the
      GenBank database, strongly suggesting that novel carboxypeptidase families or
      microbial niches exist in the activated sludge. We also observed numerous
      carboxypeptidase sequences that were much closer to those from representative
      strains present in industrial and sewage treatment and bioremediation.
      Thermostable and halotolerant carboxypeptidase sequences were also detected in
      clusters alpha and beta. Coexistence of various carboxypeptidases is evidence of
      a diverse microflora in the activated sludge, a feature suggesting a valuable
      gene resource to be further explored for biotechnology application.

PMID- 24860283
TI  - Assessment of biological colonization of historic buildings in the former
      Auschwitz II-Birkenau concentration camp.
AB  - The objective of this study was to assess biological colonization of wooden and
      brick buildings in the former Auschwitz II-Birkenau concentration camp, and to
      identify the organisms colonizing the examined buildings. Microbiological
      analysis did not reveal increased microbial activity, and the total microbial
      count of the barrack surfaces did not exceed 103 CFU/100 cm2. However, certain
      symptoms of biodegradation of the buildings were observed. The predominant
      microflora consisted of bacteria of the genera Bacillus, Sporosarcina,
      Pseudomonas, Micrococcus, Streptomyces, and Staphylococcus, as well as fungi of
      the genera Acremonium, Cladosporium, Alternaria, Humicola, Penicillium, and
      Chaetomium. The microflora patterns varied both in wooden and brick buildings.
      The structural elements of wooden and brick barracks, and especially of the
      floors and lower parts of bathroom walls, were infected by cyanobacteria and
      algae, with the most numerous being cyanobacteria of the genera Scytonema,
      Chroococcus, Gloeothece, Leptolyngbya, diatoms of the genus Diadesmis, and
      chlorophytes of the genera Chlorella and Apatococcus. The outer surfaces of the
      examined buildings were primarily colonized by lichens and bryophytes, with
      nearly 30 species identified. The dominant species of lichens belonged to the
      genera Candelariella, Caloplaca, Lecanora, Lecidea, Lepraria, Physcia, and
      Protoparmeliopsis, and those of bryophytes to the genera Bryum, Ceratodon,
      Marchantia, and Tortula. The quantity and species diversity of lichens and mosses
      were much lower in wooden barracks than in brick ones. The external surfaces of
      those barracks were only affected by Lecanora conizaeoides, Lecanora symmicta,
      Lepraria cf. incana, and Strangospora pinicola. The study results revealed vast
      biodiversity among the species colonizing historic buildings. The presence of
      these groups of organisms, resulting from their natural expansion in the
      environment, is undesirable, as their excessive growth and spread may lead to
      progressive biodegradation of buildings. Our assessment of biological
      contamination will enable the development of a disinfection and conservation plan
      for the examined buildings.

PMID- 24860284
TI  - Hexa-aqua-nickel(II) di-hydrogen hypodiphosphate.
AB  - The asymmetric unit of the title compound, [Ni(H2O)6](H2P2O6), contains one-half
      of the hexa-aqua-nickel(II) cation and one-half of the di-hydrogen
      hypodiphosphate anion. In the complex cation, the Ni(2+) atom is located on an
      inversion center and has an octa-hedral coordination sphere. The P-P distance in
      the centrosymmetric anion is 2.1853 (7) A. In the crystal, discrete
      [Ni(H2O)6](2+) cations and (H2P2O6)(2-) anions are stacked in columns parallel to
      the c axis and are linked into a three-dimensional network by medium-strength O
      H?O hydrogen bonds. 

PMID- 24860285
TI  - Bis[MU-N-(pyridin-2-yl)methane-sulfon-amido-kappa(2) N:N']silver(I).
AB  - In the title compound, [Ag2(C6H7N2O2S)2], the Ag(I) atom is coordinated by two N
      atoms from two N-(pyridin-2-yl)methane-sulfonamidate anions in a slightly bent
      linear geometry [N-Ag-N = 166.03 (7) degrees ]. The Ag(I) atoms are bridged by
      the N-(pyridin-2-yl)methane-sulfonamidate anions, forming a centrosymmetric
      dinuclear mol-ecule, in which the Ag?Ag distance is 2.7072 (4) A. 

PMID- 24860286
TI  - MU-Hexa-thio-metadiphosphato-bis-[(1,4,7,10,13,16-hexa-oxa-cyclo-octa-decane
      kappa(6) O)rubidium] aceto-nitrile disolvate.
AB  - The asymmetric unit of the title compound, [Rb2(P2S6)(C12H24O6)2].2CH3CN,
      contains one half of an [Rb(18-crown-6)2]2[P2S6] unit and one aceto-nitrile
      solvent mol-ecule. The [Rb(18-crown-6)]2[P2S6] unit is completed by inversion
      symmetry. Its Rb(+) ion is situated near the centre of the macrocyclic cavity,
      but is displaced by 0.8972 (1) A from the O atoms of the crown in the direction
      of the [P2S6](2-) moiety. The overall coordination number of the cation is eight,
      defined by the six crown ether O atoms and by two terminal S atoms of the
      [P2S6](2-) anion. The hexa-thio-metadiphosphate anion is built up from two tetra
      hedral PS4 units joined together by a common edge. The crystal structure is
      characterized by alternating layers of [Rb(18-crown-6)]2[P2S6] and aceto-nitrile
      solvent mol-ecules stacked along [010]. 

PMID- 24860287
TI  - Ethane-1,2-diaminium 2,2'-[tereph-thal-oyl-bis(aza-nedi-yl)]di-acetate
      tetrahydrate.
AB  - In the title salt hydrate, C2H10N2 (2+).C12H10N2O6 (2-).4H2O, each of the ions is
      located about a centre of inversion and the asymmetric unit is completed by two
      water molecules in general positons. In the crystal, the cations, anions and
      water mol-ecules are connected by O-H?O and N-H?O hydrogen bonding into a three
      dimensional network. 

PMID- 24860288
TI  - N,N'-Dimethyl-N''-(trichloroacet-yl)phospho-ramide.
AB  - In the title compound, C4H9Cl3N3O2P or CCl3C(O)NHP(O)(NHCH3)2, the P atom has a
      strongly distorted tetra-hedral geometry due to the formation of intermolecular
      strong hydrogen bonds involving the N atoms. In the crystal, N-H?O=P and N-H?O=C
      hydrogen bonds connect the mol-ecules into a two-dimensional array parallel to
      (100). An intra-molecular P?O contact [P?O = 2.975 (3) A] is observed. The CCl3
      group is rotationally disordered, with occupancies of 0.60 (3) and 0.40 (3). 

PMID- 24860289
TI  - (E)-1-[2-(4-Chloro-2-nitro-styr-yl)-1-phenyl-sulfonyl-1H-indol-3-yl]propan-1-one.
AB  - In the title compound, C25H19ClN2O5S, the phenyl ring forms dihedral angles of
      79.62 (12) and 80.02 (13) degrees  with the indole ring system and the benzene
      ring, respectively. The nitro group is twisted at an angle of 22.39 (11) degrees 
      with respect to the attached benzene ring. In the crystal, mol-ecules assemble
      into double layers in the ab plane via C-H?O inter-actions. 

PMID- 24860290
TI  - 2,4,6-Tri-nitro-phenyl 4-bromo-benzoate.
AB  - In the title benzoate derivative, C13H6BrN3O8, the benzene rings form a dihedral
      angle of 80.90 (9) degrees . The ester moiety forms dihedral angles of 3.2 (2)
      and 82.8 4(10) degrees  with the benzene and picryl rings, respectively. The Br
      atom is disordered over two positions, with the site occupancy for the minor
      component being 0.48 (4). The crystal structure features C-H?O inter-actions,
      which generate a three-dimensional network. 

PMID- 24860291
TI  - A triclinic polymorph of (-)-(S)-N-benzyl-2-[(R)-6-fluoro-chroman-2-yl]-2-hy
      droxy-ethanaminium bromide.
AB  - The title salt, C18H21FNO2 (+).Br(-), determined at 115 K, crystallizes in the
      triclinic space group P1. The previously reported polymorph occurs in the
      monoclinic space group P21 and has two independent mol-ecules in the asymmetric
      unit [Peeters et al. (1993 ?). Acta Cryst. C49, 2157-2160]. In the title
      molecule, the pyran rings adopt half-chair conformations. The absolute
      configuration is S for the hy-droxy-bearing C atom and R for the asymmetric C
      atom in the di-hydro-pyran unit. In the crystal, the components are linked by N
      H?Br and O-H?Br hydrogen bonds, forming chains along the c-axis direction. The
      crystal studied was refined as an inversion twin. 

PMID- 24860292
TI  - A P212121 polymorph of (+)-clusianone.
AB  - The title compound, C33H42O4 [systematic name: (1S,5S,7R)-3-benzoyl-4-hy-droxy
      8,8-dimethyl-1,5,7-tris-(3-methyl-but-2--enyl)bi-cyclo-[3.3.1]nona-3-ene-2,9
      dione], has a central bi-cyclo-[3.3.1]nonane-2,4,9-trione surrounded by tetra
      prenyl-ated and benzoyl groups. The compound was recrystallized several times in
      methanol using both a slow evaporation method and with a crystal-seeding
      technique. This subsequently produced diffraction-quality crystals which
      crystallize in the ortho-rhom-bic space group P212121, in contrast to a previous
      report of a structure determination in the Pna21 space group [McCandlish et al.
      (1976 ?). Acta Cryst. B32, 1793-1801]. The title compound has a melting point of
      365-366 K, and a specific rotation [alpha](20) value of +51.94 degrees . A strong
      intra-molecular O-H?O hydrogen bond is noted. In the crystal, mol-ecules are
      assembled in the ab plane by weak C-H?O inter-actions. 

PMID- 24860293
TI  - Ethyl 3-(10-bromo-anthracen-9-yl)-5-methyl-1,2-oxazole-4-carboxyl-ate.
AB  - In the title compound, C21H16BrNO3, the mean planes of the anthracene tricycle
      and isoxazole ring are inclined to each other at a dihedral angle of 72.12 (7)
      degrees . The carb-oxy group is slightly out of the isoxazole mean plane, with a
      maximum deviation of 0.070 (5) A for the carbonyl O atom. In the crystal, pairs
      of weak C-H?O hydrogen bonds link the mol-ecules into dimers, and weak C-H?N
      inter-actions further link these dimers into corrugated layers parallel to the bc
      plane. 

PMID- 24860294
TI  - (-)-Benzyl 2,3-dide-oxy-beta-d-erythro-hex-2-eno-pyran-oside.
AB  - In the title compound, C13H16O4, the six-membered ring of the sugar moiety shows
      a half-chair conformation. In the crystal, mol-ecules are connected via O-H?O
      hydrogen bonds, forming columns around twofold screw axes along the b-axis
      direction. There is a disorder of the benz-yloxy group, which has two possible
      orientations with the phenyl group lying on a common plane [site-occupancy
      factors = 0.589 (9) and 0.411 (9)]. 

PMID- 24860295
TI  - 2-Meth-oxy-3-(tri-methyl-sil-yl)phenyl-boronic acid.
AB  - The mol-ecular structure of the title compound, C10H17BO3Si, features an intra
      molecular O-H?O hydrogen bond; the boronic group group has an exo-endo
      conformation. In the crystal, the mol-ecules inter-act with each other by O-H?O
      hydrogen bonds, producing centrosymmetric dimers that are linked by weak pi-pi
      stacking inter-actions featuring specific short B?C contacts [e.g. 3.372 (2) A],
      forming an infinite columnar structure aligned along the a-axis direction. 

PMID- 24860296
TI  - 4-[(tert-Butyl-diphenyl-sil-yloxy)meth-yl]pyridazin-3(2H)-one.
AB  - In the title compound, C21H24N2O2Si, the carbonyl group of the heterocyclic ring
      and the O atom of the silyl ether group are placed toward opposite sides and the
      tert-butyl and pyridazinone moieties are anti-oriented across the Si-O bond
      [torsion angle = -168.44 (19) degrees ]. In the crystal, mol-ecules are assembled
      into inversion dimers through co-operative N-H?O hydrogen bonds between the NH
      groups and O atoms of the pyridazinone rings of neighbouring mol-ecules. The
      dimers are linked by pi-pi inter-actions involving adjacent pyridazinone rings
      [centroid-centroid distance = 3.8095 (19) A], generating ladder-like chains along
      the b-axis direction. The chains are further linked into a two-dimensional
      network parallel to the ab plane through weak C-H?pi inter-actions. 

PMID- 24860297
TI  - beta-Nb9VO25.
AB  - The title compound, nona-niobium vanadium penta-cosa-oxide, was prepared by a
      solid-state reaction at 1198 K. It is isotypic with Nb9AsO25, Nb9PO25 and
      Ta9VO25. The structure consists of NbO6 octa-hedra (one with 4/m.. and two with
      m.. symmetry) and VO4 tetra-hedra (-4.. symmetry) sharing corners and edges to
      form a three-dimensional framework. This framework can be considered as a
      junction between ribbons made up from NbO6 octa-hedra and chains of NbO6 octa
      hedra and chains of VO4 tetra-hedra. The V site shows half-occupancy, hence one
      half of the VO4 tetra-hedra is unoccupied. The structural differences with alpha
      Nb9VO25, VOSO4, SbOPO4 and NbOPO4 oxides are discussed. 

PMID- 24860298
TI  - Poly[(MU4-decanedio-ato)cobalt(II)].
AB  - In the title compound, [Co(C10H16O4)] n , the Co(II) atom is bonded in a slightly
      distorted tetra-hedral environment by four O atoms from the bridging sebacate
      dications, comprising two separate half-ligands which lie across crystallographic
      inversion centres. In the three-dimensional network coordination polymer, there
      are two different spatial extensions of Co(II) atoms, one with the Co(II) atoms
      lying parallel to (100) [Co?Co = 4.653 (1) A], the other lying parallel to (010)
      [Co?Co = 4.764 (1) A]. 

PMID- 24860299
TI  - Bis[bis-(2,2'-bi-pyridine-kappa(2) N,N')(carbon-ato-kappa(2) O,O')cobalt(III)] 2
      {4-[(carboxyl-atometh-yl)carbamo-yl]benz-amido}-acetate hexa-hydrate.
AB  - The complex cation of the title compound, [Co(CO3)(C10H8N2)2]2(C12H10N2O6).6H2O,
      contains a Co(III) atom with a distorted octa-hedral coordination environment
      formed by four N atoms from two bidentate 2,2'-bi-pyridine ligands and one
      bidentate carbonate anion. The asymmetric unit is completed by one-half of the 2
      ({4-[(carboxyl-atometh-yl)carbamo-yl]phen-yl}formamido)-acetate dianion, which is
      located on a centre of inversion, and by three water mol-ecules. Two
      [Co(CO3)(C10H8N2)2](+) cations are connected through C-H?O contacts by the
      uncoordinating anions. The aromatic rings of the 2,2'-bi-pyridine ligands and di
      acetate anions are involved in pi-pi stacking and C-H?pi inter-actions. The
      centroid-centroid distances are in the range 3.4898 (4)-3.6384 (5) A. The crystal
      structure is stabilized by further O-H?O and N-H?O hydrogen bonds, which give
      rise to a three-dimensional supra-molecular network. 

PMID- 24860300
TI  - Bis[2,6-bis-(1H-pyrazol-1-yl)pyridine]-deca-kis-(MU2-3-nitro-benzoato)bis-(3
      nitro-benzoato)tetra-dysprosium(III): a linear tetra-nuclear dysprosium compound
      based on mixed N- and O-donor ligands.
AB  - The title compound, [Dy4(C7H4NO4)12(C11H9N5)2] or Dy4(L1)12(L2)2, where HL1 = 3
      nitro-benzoic acid and HL2 = 2,6-bis-(1H-pyrazol-1-y1)pyridine, is a linear tetra
      nuclear complex possessing inversion symmetry. The two central inversion-related
      Dy(III) atoms are seven-coordinate, DyO7, with a monocapped triangular-prismatic
      geometry. The outer two Dy(III) atoms are eight-coordinate, DyO5N3, with a
      bicapped triangular-prismatic geometry. The outer adjacent Dy(III) atoms are
      bridged by three L1(-) carboxyl-ate groups, while the inner inversion-related
      Dy(III) atoms are bridged by four L1(-) carboxyl-ate groups. The L2 ligands are
      terminally coordinated to the outer Dy(III) atoms in a tridentate manner. In the
      crystal, mol-ecules are linked via C-H?O hydrogen bonds, forming a two
      dimensional network parallel to (001). Two carboxyl-ate O atoms, and N and O
      atoms of three nitro groups, are disordered over two positions, with a refined
      occupancy ratio of 0.552 (6):0.448 (6). 

PMID- 24860301
TI  - (MU2-2-Meth-oxy-ethanol-kappa(3) O (1):O (1),O (3))(2-meth-oxy-ethanol-kappaO
      (1))tris-(MU2-3,4,5,6-tetra-fluoro-o-phenyl-ene-kappa(2) C (1):C
      (2))trimercury(II).
AB  - In the title compound, [Hg3(C6F4)3(C3H8O2)2], two O atoms from one 2-meth-oxy
      ethanol ligand and one O atom from the second 2-meth-oxy-ethanol ligand
      coordinate three Hg(II) atoms [Hg-O = 2.765 (7)-2.890 (8) A] in the trimeric
      organomercurial Lewis acid (o-C6F4Hg)3. The hy-droxy groups are involved in
      formation of intra- and inter-molecular O-H?O hydrogen bonds; the latter link two
      mol-ecules into centrosymmetric dimers. An extensive net of weak inter-molecular
      C-H?F inter-actions further consolidates the crystal packing. 

PMID- 24860302
TI  - Tri-chlorido-(1-ethyl-piperazin-1-ium)cobalt(II).
AB  - In the title complex, [Co(C6H15N2)Cl3], the Co(2+) ion is coordinated in a
      distorted tetra-hedral fashion by three chloride ions and one N atom of the
      piperazine ring; the ring adopts a chair conformation with the N-Co and N-CEt
      bonds in equatorial orientations. In the crystal, mol-ecules are connected by N
      H?Cl hydrogen bonds, generating (10-1) sheets. 

PMID- 24860304
TI  - 1:1 Co-crystal of 4,4'-(ethene-1,2-di-yl)dipyridin-1-ium sulfate and hexa-aqua
      iron(II) sulfate monohydrate.
AB  - In the title hydrated double salt, 4,4'-(ethene-1,2-di-yl)dipyridin-1-ium hexa
      aqua-iron(II) bis-(sulfate) monohydrate, (C12H12N2)[Fe(H2O)6](SO4)2.H2O, the
      Fe(II) cation is coordin-ated by six water mol-ecules in a slightly distorted
      octa-hedral geometry; the two pyridine rings of the 4,4'-(ethene-1,2-di
      yl)dipyridin-1-ium cation are twisted to each other by a dihedral angle of 11.84
      (10) degrees . In the crystal, the cations, sulfate anions and water mol-ecules
      of crystallization are linked by O-H?O, N-H?O and weak C-H?O hydrogen bonds,
      forming a three-dimensional supra-molecular network. 

PMID- 24860303
TI  - Piperazine-1,4-diium bis-(hexa-hydroxido-hepta-oxidohexa-borato-kappa(3)
      O,O',O'')cobaltate(II) hexa-hydrate.
AB  - In the title hydrate, (C4H12N2)[Co{B6O7(OH)6}2].6H2O, both the dication and
      dianion are generated by crystallographic inversion symmetry. The Co(2+) ion in
      the dianion adopts a fairly regular CoO6 octa-hedral coordination geometry
      arising from the two O,O',O''-tridentate ligands. In the crystal, the dianions
      and water mol-ecules are linked by O-H?O hydrogen bonds, generating a framework
      with large [100] channels, which are occupied by the organic dications. N-H?O and
      C-H?O hydrogen bonds consolidate the structure. 

PMID- 24860305
TI  - Poly[[tetra-MU-cyanido-kappa(8) C:N-dodeca-cyanido-kappa(12) C-tris-(N,N-di
      methyl-formamide-kappaO)tris-(methanol-kappaO)tris-(3,4,7,8-tetra-methyl-1,10
      phenanthroline-kappa(2) N,N')trimanganese(II)ditungstate(V)] dihydrate].
AB  - The asymmetric unit of the title compound,
      {[Mn3{W(CN)8}2(C16H16N2)3(C3H7NO)3(CH3OH)3].2H2O} n , consists of three [Mn(N,N
      di-methyl-formamide)(methanol)(3,4,7,8-tetra-methyl-1,10-phenanthroline)](2+)
      cations, two [W(CN)8](3-) anions and two water mol-ecules. Each water mol-ecule
      is disordered over three sets of sites, with a refined occupancy ratio of 0.310
      (9):0.275 (9):0.415 (9) for one mol-ecule and 0.335 (9):0.288 (9):0.377 (9) for
      the other mol-ecule. The Mn(II) atoms exhibit a distorted octa-hedral geometry,
      while the W(V) atoms adopt a distorted square-anti-prismatic geometry. The Mn(II)
      and W(V) atoms are linked alternatively through cyanide groups, forming a tetra
      nuclear 12-atom rhombic metallacycle. Adjacent metallacycles are further
      connected by MU2-bridging cyanide anions, generating a 3,2-chain structure
      running parallel to [101]. Inter-chain pi-pi inter-actions are observed [centroid
      centroid distances = 3.763 (3) and 3.620 (2) A]. 

PMID- 24860306
TI  - (MU-Di-hydrogen pyrazine-2,3,5,6-tetra-carboxyl-ato-kappa(6) O (2),N (1),O (6);O
      (3),N (4),O (5))bis-(di-aqua-lithium) monohydrate.
AB  - The structure of the title compound, [Li2(C8H2N2O8)(H2O)4].H2O, is composed of
      dinuclear mol-ecules in which the ligand bridges two symmetry-related Li(I) ions,
      each coordinated also by two water O atoms, in an O,N,O'-manner. The Li and N
      atoms occupy special positions on twofold rotation axes, whereas a crystal water
      mol-ecule is located at the inter-section of three twofold rotation axes. The
      Li(I) cation shows a distorted trigonal-bipyramidal coordination. Two carboxyl
      ate groups remain protonated and form short inter-ligand hydrogen bonds. The mol
      ecules are held together by a network of hydrogen bonds in which the coordinating
      and solvation water mol-ecules act as donors and carboxyl-ate O atoms as
      acceptors, forming a three-dimensional architecture. 

PMID- 24860307
TI  - Di-chlorido-(4-{[(quinolin-2-yl)methyl-idene]amino}phenol-kappa(2)
      N,N')mercury(II).
AB  - In the mononuclear title complex, [HgCl2(C16H12N2O)], synthesized from the
      phenolic Schiff base 4-[(quinolin-2-yl-methyl-idene)amino]-phenol (QMAP), the
      coordination geometry around Hg(2+) is distorted tetra-hedral, comprising two Cl
      atoms [Hg-Cl = 2.3565 (12) and 2.5219 (12) A] and two N-atom donors from the QMAP
      ligand, viz. one imine and the other quinoline [Hg-N = 2.392 (2) and 2.237 (2) A,
      respectively]. In the crystal, O-H?Cl hydrogen bonds generate a chain structure
      extending along the c-axis direction. Weak C-H?Cl and pi-pi stacking inter
      actions [minimum ring centroid separation = 3.641 (3) A] give an overall layered
      structure lying parallel to (001). 

PMID- 24860308
TI  - Poly[diaquatris(MU6-4,6-dioxo-1,4,5,6-tetra-hydro-1,3,5-triazine-2
      carboxylato)tripotassium].
AB  - The asymmetric unit of the title compound, [K3(C4H2N3O4)3(H2O)2] n , contains two
      potassium cations (one in general position, one located on a twofold rotation
      axis), one and a half oxonate anions (the other half generated by twofold
      symmetry) and one water mol-ecule. As a result of the twofold symmetry, one H
      atom of the symmetric anion is statistically occupied. Both potassium cations are
      surrounded by eight oxygen atoms in the form of distorted polyhedra. Adjacent
      cations are inter-connected by oxygen bridges, generating layers parallel to
      (100). The aromatic ring system of the oxonate anions link these layers into a
      network structure. The crystal packing is stabilized by N-H?O, O-H?O and O-H?N
      hydrogen bonds, three of which are bifurcated. In addition, inter-molecular pi-pi
      stacking inter-actions exist between neighboring aromatic rings with a centroid
      centroid distance of 3.241 (2) A. 

PMID- 24860309
TI  - Bis{MU-cis-1,3-bis-[(di-tert-butyl-phosphan-yl)-oxy]cyclo-hexane-kappa(2)
      P:P'}bis-[carbonylnickel(0)] including an unknown solvent molecule.
AB  - The title compound, [Ni2(C22H46P2O2)2(CO)2], is located about a centre of
      inversion with the Ni(0) atom within a distorted trigonal-planar geometry. The
      cyclo-hexyl rings are in the usual chair conformation with the 1,3-cis
      substituents equatorially oriented. No specific inter-molecular inter-actions are
      noted in the crystal packing. A region of disordered electron density, most
      probably a disordered deuterobenzene solvent molecule, was treated using the
      SQUEEZE routine in PLATON [Spek (2009 ?). Acta Cryst. D65, 148-155]. Its formula
      mass and unit-cell characteristics were not taken into account during refinement.

PMID- 24860310
TI  - 1,4-Diazo-niabi-cyclo-[2.2.2]octane tetra-chlorido-cadmate(II) monohydrate.
AB  - The asymmetric unit of the title compound (C6H14N2)[CdCl4].H2O contained one 1,4
      di-aza-bicyclo-[2.2.2]octane dication, a tetrahedral CdCl4 (2-) anion and a
      lattice water mol-ecule. In the crystal, the solvate water mol-ecule inter-acts
      with the cationic and anionic species via N-H?O and O-H?Cl [O?Cl = 3.289 (7) A]
      hydrogen-bond inter-actions, respectively, leading to a layered supramolecular
      structure extending parallel to (011). 

PMID- 24860311
TI  - (4-Fluoro-phen-yl-kappaC)(N,N,N',N'-tetra-methyl-ethylenedi-amine-kappa(2)
      N,N')(tri-fluoro-meth-yl-kappaC)palladium(II).
AB  - In the title compound, [Pd(CF3)(C6H4F)(C6H16N2)], the Pd(II) cation is four
      coordinated by the two N atoms of the N,N,N',N'-tetra-methyl-ethylenedi-amine
      ligand and by one C atom each from a 4-fluoro-phenyl and a tri-fluoro-methyl
      ligand, in a distorted rectangular-planar geometry, with an average deviation
      from the least-squares plane of 0.066 (2) A. The central coordination angles with
      the Pd(II) atom range from 83.14 (10) to 97.25 (12) degrees . 

PMID- 24860312
TI  - (2.2.2-Cryptand)potassium tetra-carbonyl-cobaltate(-I).
AB  - The title salt, [K(C18H36N2O6)][Co(CO)4], is an example of a classical carbonyl
      metalate. The asymmetric unit contains one cation and one tetrahedral anion, both
      in general positions. Based on comparison of the four carbonyl C-O bond lengths
      and C-Co-C angles, the anion is unperturbed by the cation, which is normal for an
      alkali metal fully encased by a cryptand cage. 

PMID- 24860313
TI  - Poly[[nona-aqua-bis-(MU-5-hy-droxy-benzene-1,3-di-carboxyl-ato)(5-hy-droxy
      benzene-1,3-di-carboxyl-ato)dicerium(III)] hexa-hydrate].
AB  - In the title coordination polymer, {[Ce2(C8H4O5)3(H2O)9].6H2O} n , the asymmetric
      unit is formed by two Ce(III) atoms, three 5-hy-droxy-benzene-1,3-di-carboxyl-ate
      ligands, nine coordinating water mol-ecules and six water mol-ecules of
      crystallization. The two Ce(III) atoms are bridged by 5-hy-droxy-benzene-1,3-di
      carboxyl-ate ligands acting in a bis-bidentate coordination mode, generating
      infinite chains along [101]. Both independent metal atoms are nine-coordinated,
      one by four O atoms from the carboxyl-ate groups of two bridging 5-hy-droxy
      benzene-1,3-di-carboxyl-ate ligands and five O atoms from water mol-ecules,
      generating a tricapped trigonal-prismatic geometry. The coordination around the
      second Ce(III) atom is similar, except that one of the water mol-ecules is
      replaced by an O atom from an additional 5-hy-droxy-benzene-1,3-di-carboxyl-ate
      ligand acting in a monodentate coordination mode and forming a capped square-anti
      prismatic geometry. 

PMID- 24860314
TI  - Di-aqua-bis-(nicotinamide-kappaN (1))bis-(thio-cyanato-kappaN)nickel(II).
AB  - In the title complex, [Ni(NCS)2(C6H6N2O)2(H2O)2], the Ni(II) ion is located on an
      inversion center and is coordinated in a distorted octa-hedral environment by two
      N atoms from two nicotinamide ligands and two water mol-ecules in the equatorial
      plane, and two N atoms from two thio-cyanate anions in the axial positions, all
      acting as monodentate ligands. In the crystal, weak N-H?S hydrogen bonds between
      the amino groups and the thio-cyanate anions form an R 4 (2)(8) motif. The
      complex mol-ecules are linked by O-H?O, O-H?S, and N-H?S hydrogen bonds into a
      three-dimensional supra-molecular structure. Weak pi-pi inter-actions between the
      pyridine rings is also found [centroid-centroid distance = 3.8578 (14) A]. 

PMID- 24860315
TI  - Bis[MU-1,3-bis-(1H-imidazol-1-yl)propane-kappa(2) N (3):N (3')]bis-(di-chlorido
      zinc) dihydrate.
AB  - The title hydrated complex, [Zn2Cl4(C9H12N4)2].2H2O, is a discrete dinuclear zinc
      complex with 1,3-bis-(1H-imidazol-1-yl)propane as the bridging ligand. The
      complex mol-ecule lies about a crystallographic inversion centre. The Zn(II) atom
      exhibits a distorted tetra-hedral coordination geometry defined by two imidazole
      N atoms and two Cl atoms. O-H?Cl hydrogen bonding between the lattice water mol
      ecules and the terminal Cl atoms of the mol-ecule lead to a two-dimensional
      structure extending parallel to (100). 

PMID- 24860316
TI  - A new polymorph of aqua-bis-(1,10-phenanthroline-kappa(2) N,N')copper(II)
      dinitrate.
AB  - The title mol-ecule, [Cu(C12H8N2)2(H2O)](NO3)2, is a new polymorph of a compound
      which up to now has been reported to crystallize space groups in C2/c and Cc. The
      crystal studied was twinned by non-merohedry (final BASF factor of 0.40043) with
      the structure being solved and refined in P-1. The Cu(II) atom is coordinated by
      four N atoms from two 1,10-phenanthroline ligands and an O atom from a water mol
      ecule in an approximate trigonal-bipyramidal geometry. Discrete entities of one
      cation and two nitrate anions are formed by water-nitrate O-H?O hydrogen bonds.
      The components are further assembled into a three-dimensional network by C-H?O
      hydrogen bonds. 

PMID- 24860317
TI  - catena-Poly[[aqua-zinc(II)]-MU-N,N'-bis-(2-cyano-3-eth-oxy-3-oxoprop-1-en
      yl)benzene-1,2-diaminido].
AB  - The slightly yellow-coloured title complex, [Zn(C18H16N4O4)(H2O)] n ,
      crystallizes with one mol-ecule in the asymmetric unit. The structure clearly
      shows the mer-eta(4) O,O,N,N-binding mode of the N,N'-bis-(2-cyano-ethyl-propeno
      yl)-1,2-di-amido-benzene ligand stabilizing the Zn centre of a distorted octa
      hedral environment. The fifth coordination site in one apical position is held by
      a coordinating solvent water mol-ecule whereas the complete octa-hedral
      coordination sphere is completed by coordination of one N atom from a CN group of
      a neighbouring mol-ecule, leading to the final polymeric structure consisting of
      zigzag staggered chains in parallel orientation along the c-axis direction.
      Between the coord-in-ated water solvent molecule and the N atoms of uncoord-in
      ated cyano-groups of neighboured units, two H-bridge bonds are formed. One of
      these H-bridge bonds is of inter- whereas the other of intra-strand nature,
      leading to a two-dimensional network parallel to (110) stabilizing the
      supramolecular structure. Six Zn-O or Zn-N bonds are found with lengths ranging
      from 2.061 (1) to 2.185 (1) A and bond angles about the Zn atom are clustered in
      the ranges 79.83 (4)-104.21 (4) and 167.05 (4)-170.28 (4) degrees . 

PMID- 24860318
TI  - Poly[(MU3-3,5-diisopropyl-4H-1,2,4-triazolato-kappa(3) N:N':N'')silver(I)].
AB  - In the polymeric title compound, [Ag(C8H14N3)] n , the Ag(I) cation is
      coordinated by three N atoms from three 3,5-diisopropyl-1,2,4-triazolate anions
      in a T-shaped geometry. The Ag(I) cation deviates from the coordination plane by
      0.014 (1) A and the N-Ag-N bond angles are 96.85 (11), 97.72 (10) and 165.39 (12)
      degrees . The triazolate anion bridges three Ag(I) cations, forming a three
      dimensional polymeric network. 

PMID- 24860319
TI  - Bis(2,2'-bipyridyl-kappa(2) N,N')chloridonickel(II) nitrate trihydrate.
AB  - In the title hydrated salt, [NiCl(C10H8N2)2](NO3).3H2O, the Ni(2+) ion is
      coordinated by two 2,2'-bipyridyl (2,2'-bpy) ligands and a chloride ion in a
      trigonal-bipyramidal geometry. The chloride ion occupies an equatorial site and
      the dihedral angle between the 2,2'-bpy ring systems is 72.02 (6) degrees . In
      the crystal, the components are linked by C-H?O and O-H?O hydrogen bonds and
      aromatic pi-pi stacking inter-actions [shortest centroid-centroid separation =
      3.635 (2) A], generating a three-dimensional network. 

PMID- 24860320
TI  - Poly[bis-(MU-2-amino-4-nitro-benzoato)di-MU-aqua-dirubidium].
AB  - In the structure of the title salt, [Rb2(C7H5N2O4)2(H2O)2] n , the asymmetric
      unit comprises two independent and different seven-coordinate Rb(+) cations, one
      forming an RbO7 polyhedron, the other a RbO6N polyhedron, each of which is
      considerably distorted. The RbO7 polyhedron comprises bridging O-atom donors from
      two water mol-ecules, three carboxyl-ate groups, and two nitro groups. The RbO6N
      polyhedron comprises the two bridging water mol-ecules, one monodentate amine N
      atom donor, one carboxyl O-atom donor and three O-atom donors from nitro groups
      (one from the chelate bridge). The extension of the dinuclear unit gives a three
      dimensional polymeric structure which is stabilized by both intra- and inter
      molecular amine N-H?O and water O-H?O hydrogen bonds to carboxyl and water O-atom
      acceptors, as well as a number of inter-ring pi-pi inter-actions [minimum
      centroid-centroid separation = 3.364 (2) A]. The title salt is isostructural with
      the analogous caesium salt. 

PMID- 24860321
TI  - Tetrakis[MU3-2-(piperidin-1-yl)ethanolato]tetrakis[chloridocopper(II)].
AB  - In the title tetra-nuclear compound, [Cu4(C7H14NO)4Cl4], each Cu(II) cation is
      N,O-chelated by a piperidineethanolate anion and coordinated by a Cl(-) anion and
      two O atoms from neighboring piperidine-ethano-late anions in a distorted NO3Cl
      square-pyramidal geometry. The deprotonated hydroxyl groups of the
      piperidineethanolate anions bridge Cu(II) cations, forming the tetra-nuclear
      complex. All piperidine rings display a chair conformation. In the crystal, there
      are no significant inter-molecular inter-actions present. The crystal studied was
      an inversion twin refined with a minor component of 0.18 (5). 

PMID- 24860322
TI  - Bis(4-hy-droxy-3-meth-oxy-benzaldehyde 4-phenyl-thio-semicarbazonato-N
      (1),S)nickel(II).
AB  - In the title compound, [Ni(C15H14N3O2S)2], the Ni(II) atom lies on a center of
      symmetry. The deprotonated ligands act as N,S-donors, forming five-membered
      metalla-rings. The Ni(II) atom is four-coordinated in a slightly distorted square
      planar environment. In the crystal, the discrete complex mol-ecules are linked by
      weak N-H?O hydrogen bonds, generating chains along [110]. The chains are further
      connected via weak O-H?N inter-actions into a layered network extending parallel
      to (001). 

PMID- 24860323
TI  - (+/-)-4,12,15,18,26-Penta-hydroxy-13,17-dioxahepta-cyclo
      [14.10.0.0(3,14).0(4,12).0(6,11).0(18,26).0(19,24)]hexa-cosa
      1,3(14),6(11),7,9,15,19,21,23-nona-ene-5,25-dione methanol disolvate.
AB  - The title compound, C24H14O9.2CH3OH, displays a chair-shaped form. The two di
      hydro-indenone ring systems are located above and below the central fused-ring
      system, the dihedral angles between the mean planes of di-hydro-indenone ring
      systems and the mean plane of central fused-ring system are 67.91 (5) and 73.52
      (4) degrees , respectively. In the crystal, extensive O-H?O hydrogen bonds, weak
      C-H?O hydrogen bonds and C-H?pi inter-actions link the mol-ecules into a three
      dimensional supra-molecular architecture. 

PMID- 24860325
TI  - 3-[(E)-2-(2-Meth-oxy-phen-yl)vin-yl]-5,5-di-methyl-cyclo-hex-2-enone.
AB  - The title compound, C17H20O2, has an E conformation about the bridging C=C bond.
      The cyclo-hexene ring adopts an envelope conformation with the dimethyl
      substituted C atom as the flap. Its mean plane makes a dihedral angle of 7.20
      (12) degrees  with the benzene ring. In the crystal, neighbouring mol-ecules are
      connected via C-H?O hydrogen bonds, forming chains running along the a-axis
      direction. 

PMID- 24860324
TI  - [2-(Benzyl-idene-amino)-4,5,6,7-tetra-hydro-benzo[b]thio-phen-3-yl](phen
      yl)methanone.
AB  - In the title compound, C22H19NOS, the cyclo-hexene ring of the tetra-hydro-benzo
      thio-phenyl ring system adopts a slightly distorted half-chair conformation and
      is twisted slightly [7.5 (8) degrees  for the major disorder component] from the
      mean plane of the thio-phene ring. The dihedral angles between the mean planes of
      the thio-phene ring and the phenyl rings are 65.7 (3) and 8.3 (4) degrees . The
      phenyl rings are twisted with respect to each other by 73.8 (7) degrees .
      Disorder was modeled for four C atoms of the cyclo-hexene ring over two sets of
      sites with an occupancy ratio of 0.659 (2):0.341 (2). In the crystal, a single
      weak C-H?O inter-action links the mol-ecules into [001] chains. 

PMID- 24860326
TI  - 2,2'-[2,4-Bis(naphthalen-1-yl)cyclo-butane-1,3-di-yl]bis-(1-methyl-pyridinium)
      bis-(4-chloro-benzene-sulfonate): thermal-induced [2 + 2] cyclo-addition reaction
      of a heterostilbene.
AB  - The asymmetric unit of the title salt, C36H32N2 (2+).2C6H4ClO3S(-), consists of
      one anion and one half-cation, the other half being generated by inversion
      symmetry. The dihedral angle between the pyridinium ring and the napthalene ring
      system in the asymmetric unit is 42.86 (6) degrees . In the crystal, cations and
      anions are linked by weak C-H?O inter-actions into chains along [010]. Adjacent
      chains are further arranged in an anti-parallel manner into sheets parallel to
      the bc plane. pi-pi inter-actions are observed involving the cations, with
      centroid-centroid distances of 3.7664 (8) and 3.8553 (8) A. 

PMID- 24860327
TI  - Ethyl trans-12-(pyridin-4-yl)-9,10-ethano-anthracene-11-carboxyl-ate.
AB  - In the title compound, C24H21NO2, the residues at the central ethyl-ene bridge
      are trans to each other. The dihedral angles between the pyridine and benzene
      rings are 67.09 (6) and 61.41 (5) degrees . In the crystal, centrosymmetrically
      related mol-ecules are linked into dimers by pairs of C-H?O hydrogen bonds. 

PMID- 24860328
TI  - Methyl ({[(4E)-1,3-dimethyl-2,6-di-phenyl-piperidin-4-yl-idene]amino}
      oxy)acetate.
AB  - In the title compound, C22H26N2O3, the piperidine ring exhibits a chair
      conformation. The phenyl rings attached to the piperidine at the 2- and 6
      positions have axial orientations. These rings make a dihedral angle of 49.75
      (11) degrees . The amino-oxy acetate group attached at the 4-position has an
      equatorial orientation. In the crystal, inversion dimers linked by pairs of C
      H?pi inter-actions occur. 

PMID- 24860329
TI  - 6-Chloro-4-oxo-4H-chromene-3-carb-aldehyde.
AB  - In the title compound, C10H5ClO3, a chlorinated 3-formyl-chromone derivative, the
      non-H atoms are essentially coplanar (r.m.s. deviation = 0.0456 A) with the
      largest deviation from the least-squares plane [0.1136 (16) A] being found for
      the ring-bound carbonyl O atom. In the crystal, mol-ecules are linked through
      stacking inter-actions along the b axis [shortest centroid-centroid distance
      between the pyran and benzene rings = 3.4959 (15) A]. 

PMID- 24860330
TI  - 1-{[(Z)-Cyclo-pentyl-idene]amino}-3-phenyl-thio-urea.
AB  - The sample of the title compound, C12H15N3S, chosen for study consisted of
      triclinic crystals twinned by a 180 degrees  rotation about the a axis. The five
      membered ring adopts a twisted conformation. The dihedral angle between the
      phenyl ring and the mean plane of the thio-urea unit is 78.22 (8) degrees . In
      the crystal, molecules are linked via pairs of N-H?S hydrogen bonds forming
      inversion dimers. 

PMID- 24860331
TI  - N,N,N'-Trimethyl-N''-(4-nitro-phen-yl)-N'-phenyl-guanidine.
AB  - The C-N bond lengths in the guanidine unit of the title compound, C16H18N4O2, are
      1.298 (2), 1.353 (2) and 1.401 (3) A, indicating double- and single-bond
      character. The N-C-N angles are 115.81 (16), 118.90 (18) and 125.16 (18) degrees
      , showing a deviation of the CN3 plane from an ideal trigonal-planar geometry. In
      the crystal, C-H?O hydrogen bonds are observed between the methyl- and aromatic-H
      atoms and nitro-O atoms. One H atom of the phenyl ring and of the NMe2 group
      associate with the O atoms of the nitro group, giving chains along the a- and b
      axis directions. Cross-linking of these two chains results in a two-dimensional
      network along bc. 

PMID- 24860332
TI  - 2-[1-(4-Bromo-phen-yl)-2-nitro-eth-yl]hexa-noic acid.
AB  - In the crystal structure of the title compoud, C14H18BrNO4, mol-ecules are linked
      by a strong O-H?O hydrogen bond and weaker C-H?O inter-actions. The benzene ring
      makes dihedral angles of 3.67 (3) and 72.63 (3) degrees  with the carb-oxy-lic
      acid group and the nitro group, respectively. 

PMID- 24860333
TI  - 3,4-Di-fluoro-2-hy-droxy-benzoic acid.
AB  - In the title compound, C7H4F2O3, an intra-molecular O-H?O hydrogen bond is
      observed. In the crystal, inversion dimers linked by pairs of O-H?O hydrogen
      bonds generate R 2 (2)(8) ring motifs. These dimers are linked by C-H?O and C-H?F
      hydrogen bonds, forming sheets lying parallel to (30-1). The sheets are linked by
      aromatic pi-pi stacking inter-actions [inter-centroid distance = 3.7817 (9) A],
      forming a three-dimensional structure. 

PMID- 24860334
TI  - 5-Bromo-2,7-dimethyl-3-(4-methyl-phenyl-sulfon-yl)-1-benzo-furan.
AB  - In the title compound, C17H15BrO3S, the dihedral angle between the mean planes of
      the benzo-furan and 4-methyl-phenyl rings is 76.43 (5) degrees . In the crystal,
      mol-ecules are linked via pairs of C-H?O hydrogen bonds into inversion dimers
      that are further linked by Br?Br [3.6517 (4) A] contacts about inversion centers
      into supra-molecular sheets that lie parallel to (111). 

PMID- 24860335
TI  - (E)-3-(Oxolan-2-yl-idene)-1-phenyl-pyrrolidine-2,5-dione.
AB  - In the title compound, C14H13NO3, the dihedral angles between the central
      pyrrolidine ring and the pendant tetra-hydro-furan and phenyl rings are 5.34 (18)
      and 58.99 (17) degrees , respectively. The tetra-hydro-furan ring is almost
      planar (r.m.s. deviation = 0.008 A). In the crystal, mol-ecules are linked by C
      H?O inter-actions, generating a three-dimensional network. 

PMID- 24860336
TI  - (5-Fluoro-4'-methyl-biphenyl-3-yl)(2,4,6-tri-methyl-phen-yl)iodo-nium tri-fluoro
      methane-sulfonate.
AB  - In the title mol-ecular salt, C22H21FI(+).CF3SO3 (-), the dihedral angle between
      the rings of the biphenyl group is 65.6 (1) degrees . The ring of the mesitylene
      group is inclined to the fluoro-benzene ring at an angle of 86.1 (3) degrees  and
      the C-I-C bond angle is 97.0 (2) degrees . In the crystal, extremely short I?O
      contacts of 2.862 (5) and 2.932 (5) A occur, due to the strong electrostatic
      inter-actions between the I atom and two adjacent tri-fluoro-methane-sulfonate
      counter-ions. There are also C-H?F and C-H?pi inter-actions present: together
      with the I?O bonds, these result in a three-dimensional network. 

PMID- 24860337
TI  - Diethyl 4-oxo-4H-[1,4'-bi-quinoline]-3,3'-di-carboxyl-ate.
AB  - In the title mol-ecule, C24H20N2O5, the quinoline and quinolinone moieties are
      practically perpendicular to each other, forming a dihedral angle of 89.06 (3)
      degrees . In the crystal, each moiety forms coplanar pi-stacked couples with the
      respective inversion equivalents. The quinolinone moieties overlap with their
      benzene rings with a centroid-centroid separation of 3.641 (2) A, whereas the
      quinoline moieties overlap with their pyridine rings with a separation of 3.592
      (2) A. The resulting supra-molecular chains propargate along [101]. 

PMID- 24860338
TI  - {(3aR,5S,6R,6aR)-5-[(R)-1,2-Di-hydroxy-eth-yl]-2,2-di-methyl-tetra-hydro-furo[2,3
      d][1,3]dioxol-6-yl}methyl methane-sulfonate.
AB  - In the title compound, C11H20O8S, the furan-ose ring has a pseudorotation phase
      angle equal to 31.3 degrees  and assumes a (3) T 4 conformation, with deviations
      of 0.297 (4) and -0.152 (4) A for the corresponding C atoms. The dioxolane ring
      adopts an envelope conformation. One of the O atoms is at the flap and deviates
      from the least-squares plane formed by the other four ring atoms by 0.405 (2) A.
      The dihedral angle between the planar fragments of the rings is 63.53 (8) degrees
      . In the crystal, mol-ecules are associated into sheets perpendiculer to the b
      axis by means of O-H?O hydrogen bonds. A few weak C-H?O inter-actions are also
      observed. 

PMID- 24860339
TI  - (1R,4R,6S,7R)-5,5-Di-bromo-1,4,8,8-tetra-methyl-tri-cyclo-[5.4.1.0(4,6)]dodecan
      12-one.
AB  - The title compound, C16H24Br2O, was synthesized from the reaction of beta
      himachalene (3,5,5,9-tetra-methyl-2,4a,5,6,7,8-hexa-hydro-1H-benzo-cyclo
      heptene), which was isolated from Atlas cedar (Cedrus atlantica). The asymmetric
      unit contains two independent mol-ecules with similar conformations. Each mol
      ecule is built up from two fused seven-membered rings and an additional three
      membered ring. In both mol-ecules, one of the seven-membered rings has a chair
      conformation, whereas the other displays a screw-boat conformation. 

PMID- 24860340
TI  - Methyl 1-[(Z)-2-(benzyloxycarbonyl)hydrazin-1-ylidene]-5-chloro-2-hydroxy-indane
      2-carboxylate.
AB  - The title compound, C19H17ClN2O5, is an important inter-mediate for the synthesis
      of the pesticide Indoxacarb [systematic name: (S)-methyl 7-chloro-2-{[(meth-oxy
      carbon-yl)[4-(tri-fluoro-meth-oxy)phen-yl]amino]-carbon-yl}-2H,3H,4aH,5H-indeno
      [1,2-e][1,3,4]oxadiazine-4a-carboxyl-ate] The C=N double bond has a Z
      conformation. An intra-molecular N-H?O hydrogen bond occurs. In the crystal
      structure, O-H?O hydrogen bonds result in the formation of 12-membered rings
      lying about inversion centers with R (4) 4(12) motifs. 

PMID- 24860341
TI  - 1-Methyl-3-phenyl-thio-urea.
AB  - The title compound, C8H10N2S, was prepared by reaction of methyl-amine solution,
      KOH and phenyl-iso-thio-cyanate in ethanol. It adopts a syn-Me and anti-Ph
      conformation relative to the C=S double bond. The dihedral angle between the N
      C(=S)-N thio-urea and phenyl planes is 67.83 (6) degrees . In the crystal, the
      mol-ecules centrosymmetrical dimers by pairs of N(Ph)-H?S hydrogen bonds. The
      dimers are linked by N(Me)-H?S hydrogen bonds into layers parallel to (100). 

PMID- 24860342
TI  - Bis(2,3-di-chloro-phen-yl) di-sulfide.
AB  - The title compound, C12H6Cl4S2, features an S-S bond [2.0252 (8) A] that bridges
      two 2,3-di-chloro-phenyl rings with a C-S-S-C torsion angle of 88.35 (11) degrees
      . The benzene rings are normal one to the other with a dihedral angle of 89.83
      (11) degrees . The crystal structure features inter-molecular Cl?Cl [3.4763 (11)
      A] and pi-pi stacking inter-actions [centroid-centroid distances = 3.696 (1) and
      3.641 (2) A]. Intra-molecular C-H?S inter-actions are also observed. 

PMID- 24860343
TI  - 9alpha-Hy-droxy-12-{[4-(4-hy-droxy-phen-yl)piperazin-1-yl]meth-yl}-4,8-dimethyl
      3,14-dioxatri-cyclo-[9.3.0.0(2,4)]tetra-dec-7-en-13-one.
AB  - The title compound, C25H34N2O5, was synthesized from 9alpha-hy-droxy-parthenolide
      (9alpha-hy-droxy-4,8-dimethyl-12-methylen-3, 14-dioxa-tri-cyclo
      [9.3.0.0(2,4)]tetra-dec-7-en-13-one), which in turn was isolated from the chloro
      form extract of the aerial parts of Anvillea radiata. The mol-ecule comprises a
      ten-membered ring fused to a five-membered ring with an additional ep-oxy ring
      system fused to the ten-membered ring. The five-membered ring also carries a 4-hy
      droxy-phenyl-piperazin-1-ylmethyl substituent. The ten-membered ring adopts an
      approximate chair-chair conformation, while the piperazine ring displays a chair
      conformation and the five-membered ring shows an envelope conformation with the C
      atom closest to the hy-droxy group forming the flap. Two C atoms in the phenyl
      ring and the O atom of the hydroxyl group are disordered over two sites, with an
      occupancy ratio of 0.53 (5):0.47 (5). An intra-molecular O-H?N hydrogen-bond
      stabilizes the mol-ecular conformation. In the crystal, C-H?O hydrogen bonds link
      the mol-ecules into zigzag chains running along the a-axis direction. 

PMID- 24860344
TI  - N'-[(E)-1-(2-Fluoro-phen-yl)ethyl-idene]pyridine-4-carbohydrazide.
AB  - The title compound, C14H12FN3O, adopts an E conformation with respect to the
      azomethine bond. The pyridyl and fluoro-benzene rings make dihedral angles of
      38.58 (6) and 41.61 (5) degrees  respectively with the central C(=O)N2CC unit,
      resulting in a non-planar mol-ecule. The inter-molecular inter-actions comprise
      two classical N-H?O and N-H?N hydrogen bonds and four non-classical C-H?O and C
      H?F hydrogen bonds. These inter-actions are augmented by a weak pi-pi inter
      action between the benzene and pyridyl rings of neighbouring mol-ecules, with a
      centroid-centroid distance of 3.9226 (10) A. This leads to a three-dimensional
      supra-molecular assembly in the crystal system. The F atom is disordered over two
      sites in a 0.559 (3): 0.441 (3) ratio, through a 180 degrees  rotation of the
      fluoro-benzene ring. 

PMID- 24860345
TI  - 4,4'-{[1,2-Phenyl-enebis(methyl-ene)]bis-(-oxy)}di-benzoic acid di-methyl
      formamide disolvate.
AB  - In the title solvate, C22H18O6.2C3H7NO, the complete dicarboxylic acid molecule
      is generated by a crystallographic twofold axis, which bisects the central
      benzene ring and one N,N-di-methyl-formamide solvent mol-ecule. The dihedral
      angle between the central and pendant benzene rings is 54.53 (5) degrees  while
      that between the pendant rings is 45.44 (5) degrees . In the crystal, the acid
      molecules are linked to the solvent molecules via O-H?O and weak C-H?O hydrogen
      bonds. Further weak C-H?O inter-actions link adjacent acid mol-ecules into a
      three-dimensional network. 

PMID- 24860346
TI  - 6,8-Di-iodo-4-oxo-4H-chromene-3-carbalde-hyde.
AB  - The title compound, C10H4I2O3, is an iodinated 3-formyl-chromone derivative, and
      the atoms are essentially coplanar [r.m.s. deviation = 0.049 A, largest deviation
      from the least-squares plane = 0.111 (9) A for the CH(=O) C atom]. In the
      crystal, mol-ecules are linked into a three-dimensional network through halogen
      bonds [I?O = 3.352 (5) and 3.405 (7) A, C-I?O = 144.2 (3) and 154.5 (3) degrees ,
      and C=O?I = 134.9 (6) and 146.0 (6) degrees ], and pi-pi stacking inter-actions
      [centroid-centroid distance = 3.527 (6) A]. 

PMID- 24860347
TI  - Bis{2-[(Tri-phenyl-meth-yl)amino]-phen-yl} diselenide aceto-nitrile monosolvate.
AB  - The mol-ecular structure of the title compound, C50H40N2Se2.C2H3N, shows a syn
      conformation of the benzene rings bound to the Se atoms, with an Se-Se bond
      length of 2.3529 (6) A and a C-Se-Se-C torsion angle of 93.53 (14) degrees . The
      two Se-bonded aromatic ring planes make a dihedral angle of 18.42 (16) degrees .
      Intra-molecular N-H?Se hydrogen bonds are noted. Inter-molecular C-H?Se inter
      actions give rise to supra-molecular chains extended along [100]. One severely
      disordered aceto-nitrile solvent mol-ecule per asymmetric unit was treated with
      SQUEEZE in PLATON [Spek (2009 ?). Acta Cryst. D65, 148-155]; the crystal data
      take the presence of this mol-ecule into account. 

PMID- 24860348
TI  - {[2-Methyl-2-(phen-oxy-meth-yl)propane-1,3-di-yl]bis-(-oxy)}di-benzene.
AB  - The title compound, C23H24O3, was obtained in a one-step (60% yield) synthesis
      from 1,1,1-tris(hydroxymethyl)ethane. It features a tripodal ligand capable of
      complexing metal centres. One of the three conformations involving the methyl
      group, the central C-C bond and the phenoxy substituents is antiperiplanar while
      the two others are synclinal [the corresponding C-C-C-O torsion angles are -174.6
      (1), -53.2 (2) and -47.3 (2) degrees ]. In the crystal, C-H?O inter-actions link
      the molecules into [010] chains. 

PMID- 24860349
TI  - Methyl 1-ethyl-3'-[hy-droxy(naphthalen-1-yl)meth-yl]-1'-methyl-2-oxo-spiro-[indo
      line-3,2'-pyrrolidine]-3'-carboxyl-ate.
AB  - In the title compound, C27H28N2O4, the pyrrolidine ring adopts a twist
      conformation. The plane of the indole ring is almost perpendicular to that of the
      pyrrolidine ring, making a dihedral angle of 88.50 (6) degrees . The planes of
      the naphthyl ring system and the pyrrolidine ring are tilted by an angle of 55.86
      (5) degrees . The mol-ecular conformation is stabilized by intra-molecular O-H?O
      and O-H?N hydrogen bonds. 

PMID- 24860350
TI  - 1'-Allyl-1-(3,4-di-methyl-benzo-yl)-2-(4-methyl-1,3-thia-zol-5-yl)-1,2,5,6,7,7a
      hexa-hydro-spiro-[pyrrolizine-3,3'-indolin]-2'-one.
AB  - In the title compound, C30H31N3O2S, the fused pyrrolidine ring bearing three
      substituents adopts an envelope conformation with the C atom bearing the benzoyl
      group as the flap. The other fused pyrrolidine ring adopts a twisted conformation
      about one of its C-C bonds. The dihedral angle between the isatin ring system and
      the methyl-thia-zole ring is 25.95 (8) degrees . An intra-molecular C-H?O inter
      action closes an S(8) ring. In the crystal, mol-ecules are linked by C-H?O inter
      actions, generating C(11) chains propagating in [001]. 

PMID- 24860351
TI  - (3-Methyl-3a,4,7,7a-tetra-hydro-5H-4,7-methano-isoxazolo[4,5-d][1,2]oxazin-5
      yl)(phen-yl)methanone.
AB  - The title compound, C14H14N2O3, is the exo isomer with a syn arrangement of two O
      atoms in the isoxazole and oxazine rings. The dihedral angle between the
      isoxazole and phenyl rings is 60.38 (4) degrees . In the crystal, weak C-H?O
      hydrogen bonds link the mol-ecules, forming a three-dimensional network. The
      isoxazole O atom is an acceptor for three of these hydrogen bonds. 

PMID- 24860352
TI  - 5,8-Dimeth-oxy-3,9-dimethyl-3a,4,9,9a-tetra-hydro-4,9-ep-oxy-naphtho-[2,3
      d]isoxazole.
AB  - The title compound, C15H17NO4, is the exo isomer with a syn arrangement of the O
      atom in the isoxazole ring to the methyl group of the bicyclic alkene. The
      dihedral angle between the isoxazole ring and the benzene ring is 7.42 (9)
      degrees . In the crystal, weak C-H?O hydrogen bonds link mol-ecules, forming a
      three-dimensional network. The isoxazole O atom is an acceptor for both weak
      hydrogen bonds. 

PMID- 24860353
TI  - 1-(3-Hy-droxy-5,8-dimeth-oxy-4-methyl-1,2,3,4-tetra-hydro-1,4-ep-oxy-naphthalen-2
      yl)ethan-1-one.
AB  - The stereochemistry and regioschemistry (exo) of the title compound, C15H18O5,
      were determined by the X-ray analysis. The meth-oxy groups essentially lie in the
      plane of the benzene ring to which they are attached, as described by the C-O-C C
      torsion angles of -176.80 (12) and 4.67 (19) degrees . In the crystal, O-H?O
      hydrogen bonds and weak C-H?O hydrogen bonds link the mol-ecules, forming chains
      of R 2 (1)(8) rings along [010]. 

PMID- 24860354
TI  - cis-2-(4-Meth-oxy-phen-yl)-4-methyl-1,2-di-hydro-naphthalen-1-ol.
AB  - The stereochemistry and regiochemistry of the title compound, C18H18O2, were
      determined by the X-ray analysis. There are two independent mol-ecules in the
      asymmetric unit in which the dihedral angles between the benzene rings are 88.31
      (4) and 86.27 (4) degrees . The cyclo-hexene rings are in half-chair
      conformations. In the crystal, O-H?O hydrogen bonds link alternating types of mol
      ecules into chains along [010] with graph-set C 2 (2)(4). 

PMID- 24860355
TI  - 6-Chloro-8-nitro-4-oxo-4H-chromene-3-carbaldehyde.
AB  - In the title compound, C10H4ClNO5, the non-H atoms of the 6-chloro-chromone unit
      are coplanar (r.m.s. deviation = 0.017 A) with the largest deviation from the
      mean plane [0.031 (2) A] being found for the C=O C atom. The nitro group (NO2) is
      inclined to the chromone unit mean plane by 13.3 (2)  degrees . The formyl group
      is also twisted with respect to the attached ring [C-C-C-O torsion angles = 10.8
      (4) and -171.8 (2) degrees ]. In the crystal, mol-ecules are linked via C-H?O
      hydrogen bonds forming slab-like networks lying parallel to (-301). The slabs are
      linked by pi-pi inter-actions involving the benzene rings of the chromone units
      [centroid-centroid distance = 3.770 (3) A]. 

PMID- 24860356
TI  - Diethyl [(4-nitrobenzamido)(phen-yl)meth-yl]phospho-nate.
AB  - In the title compound, C18H21N2O6P, the dihedral angle between the benzene and
      phenyl rings is 85.1 (2) degrees . In the crystal, mol-ecules are linked via
      pairs of N-H?O(=P) hydrogen bonds, forming inversion dimers with graph-set
      notation R 2 (2)(10). One of the ethyl groups is disordered over two sets of
      sites, with occupancies 0.746 (11) and 0.254 (11). 

PMID- 24860357
TI  - 2-(Tri-methyl-aza-nium-yl)ethyl hydrogen phosphate (phospho-choline) mono
      hydrate.
AB  - In the crystal structure of the title compound, C5H14NO4P.H2O, the zwitterionic
      phospho-choline mol-ecules are connected by an O-H?O hydrogen bond between the
      phosphate groups, forming a zigzag chain along the b-axis direction. The chains
      are further connected through O-H?O hydrogen bonds involving water mol-ecules,
      forming a layer parallel to (101). Three and one C-H?O inter-actions are also
      observed in the layer and between the layers, respectively. The conformation of
      the N-C-C-O backbone is gauche with a torsion angle of -75.8 (2) degrees  

PMID- 24860358
TI  - (Z)-N-[1-(Aziridin-1-yl)-2,2,2-tri-fluoro-ethyl-idene]-4-bromo-aniline.
AB  - The title compound, C10H8BrF3N2, crystallizes with two independent mol-ecules in
      the asymmetric unit, which can be considered as being related by a pseudo
      inversion center, so their conformations are different; the corresponding N=C-N-C
      torsion angles are 54.6 (5) and -50.5 (5) degrees . In the crystal, mol-ecules
      related by translation in [001] inter-act through short inter-molecular Br?F
      contacts [3.276 (2) and 3.284 (2) A], thus forming two types of
      crystallographically independent chains. 

PMID- 24860359
TI  - (E)-3-Isopropyl-1-methyl-2,6-di-phenyl-piperidin-4-one O-nicotinoyl oxime.
AB  - In the title compound, C27H29N3O2, the piperidine ring exists in a chair
      conformation with an equatorial orientation of the phenyl and methyl
      substituents. The C-C=N bond angles are significantly different [119.1 (2) and
      127.2 (2) degrees ]. The phenyl rings are inclined to one another by 44.90 (14)
      degrees , and by 80.85 (13) and 79.62 (12) degrees  to the mean plane of the
      piperidine ring. The terminal pyridine ring is inclined to the piperidine ring
      mean plane by 74.79 (15) degrees . In the crystal, mol-ecules are linked by C
      H?pi inter-actions, forming a three-dimensional network. 

PMID- 24860360
TI  - Diethyl 2,2'-(ethane-1,2-diyldi-oxy)di-benzo-ate.
AB  - The mol-ecular title compound, C20H22O6, was obtained by the reaction of ethyl 2
      hy-droxy-benzoate with 1,2-di-chloro-ethane. The mol-ecule lies on a twofold
      rotation axis which passes through the middle of the central ethyl-ene bridge.
      This group exhibits a gauche conformation with the corresponding O-C-C-O torsion
      angle being 73.2 (2) degrees . The C atoms of the carboxyl group, the aryl and
      the O-CH2 group are coplanar, with an r.m.s. deviation of 0.01 A. The two aryl
      rings form a dihedral angle of 67.94 (4) degrees . The ester ethyl group is
      disordered over two sets of sites with an occupancy ratio of 0.59 (2):0.41 (2).
      The crystal packing is dominated by van der Waals forces. 

PMID- 24860361
TI  - 2-Thio-ureido-1H-benzimidazol-3-ium chloride monohydrate.
AB  - In the title compound, C8H9N4S(+).Cl(-).H2O, the cation is approximately planar,
      with a dihedral angle of 7.71 (8) degrees  between the mean planes of the benzo
      imidazole ring system and the thio-urea unit. In the crystal, cations, anions and
      water molecules of crystallization are linked by O-H?Cl, N-H?O, N-H?Cl and N-H?S
      hydrogen bonds into a three-dimensional network. pi-pi stacking is observed
      between the benzene and imidazole rings of neighbouring mol-ecules, the centroid
      centroid distance being 3.5774 (11) A. 

PMID- 24860362
TI  - N-Benzyl-2-chloro-quinazolin-4-amine.
AB  - The asymmetric unit of the title compound, C15H12ClN3, contains two independent
      mol-ecules. The quinazoline ring system in each is essentially planar, with
      maximum deviations of 0.025 (16) and 0.0171 (16) A. The dihedral angles between
      quinazoline ring systems and the phenyl rings are 88.25 (8) and 85.28 (16)
      degrees  in the two independent mol-ecules. In the crystal, alternating
      independent mol-ecules are linked by N-H?N hydrogen bonds, forming chains along
      [001]. 

PMID- 24860363
TI  - 6-Bromo-4-oxo-4H-chromene-3-carb-alde-hyde.
AB  - In the title compound, C10H5BrO3, a brominated 3-formyl-chromone derivative, the
      non-H atoms are essentially coplanar (r.m.s. deviation = 0.0420 A), with the
      largest deviation from its mean plane [0.109 (2) A] being found for the ring
      bound carbonyl O atom. In the crystal, mol-ecules are linked through halogen
      bonds [Br?O = 3.191 (2) A, C-Br?O = 167.32 (10) degrees  and C=O?Br = 168.4 (2)
      degrees ] along [101]. Mol-ecules are assembled into layers parallel to (101) via
      pi-pi stacking inter-actions along the b axis [shortest centroid-centroid
      distance between the pyran and benzene rings = 3.495 (2) A]. 

PMID- 24860364
TI  - (E)-tert-Butyl 2-(5-{[4-(dimethylamino)phenyl]diazenyl}-2,6-dioxo-1H-pyrimid-in-3
      yl)acetate dichloromethane monosolvate.
AB  - In the title compound, C18H23N5O4.CH2Cl2, the di-chloro-methane solvent mol-ecule
      is disordered over two sets of sites in a 0.630 (13):0.370 (13) ratio. The
      dihedral angle between the uracil and phenyl rings is 30.2 (1) degrees . In the
      crystal, the principal inter-actions are N-H?O hydrogen bonds, which link uracil
      units across centres of symmetry, forming eight-membered rings with an R (2) 2(8)
      graph-set motif. The structure also displays C-H?O and C-H?Cl hydrogen bonds.
      Intra-molecular C-H?O short contacts are also observed. 

PMID- 24860365
TI  - 2,8,15,18,21,24,31,37,44,47,50,53-Dodeca-oxahepta-cyclo
      [52.4.0.0(4,35).0(6,33).0(9,14).0(25,30).0(38,43)]octa-penta-conta
      1(54),4,6(33),9(14),10,12,25(30),26,28,34,38(43),39,41,55,57-penta-deca-ene di
      chloro-methane disolvate.
AB  - In the title compound, C46H50O12.2CH2Cl2, each dual 20-crown-6 unit crystallizes
      with two di-chloro-methane solvent mol-ecules. The crown unit mol-ecule lies
      about an inversion centre located at the central benzene ring. The two crown ring
      groups adopt an anti conformation, stabilized by weak intra-molecular C-H?O inter
      actions. In the crystal, the crown unit mol-ecules and the solvent mol-ecules are
      linked by C-H?O inter-actions into a three-dimensional network. 

PMID- 24860366
TI  - 2-(5-Methyl-1,3,4-oxa-diazol-2-yl)phenyl acetate.
AB  - In the title compound, C11H10N2O3, which is a potential bioactive compound, the
      benzene and oxa-diazole rings are approximately coplanar, with an inter-ring
      dihedral angle of 4.14 (2) degrees , while the ester plane is rotated out of the
      benzene plane [dihedral angle = 82.69 (9) degrees ]. In the crystal, the mol
      ecules form layers down the a axis with weak pi-pi inter-actions between the oxa
      diazole and benzene rings [minimum ring centroid separation = 3.7706 (14) A]. 

PMID- 24860367
TI  - 5-(4-Chloro-phen-oxy)-3-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde.
AB  - In the title compound, C17H13ClN2O2, the phenyl and chloro-benzene rings are
      inclined to the central pyrazole ring at 40.84 (9) and 65.30 (9) degrees ,
      respectively. In the crystal, pairs of C-H?pi inter-actions link the mol-ecules
      into inversion dimers and C-H?O hydrogen bonds link these dimers into columns
      extended in [010]. The crystal packing exhibits short inter-molecular O?Cl
      contacts of 3.0913 (16) A. 

PMID- 24860368
TI  - Methyl 4-O-benzyl-alpha-l-rhamno-pyrano-side.
AB  - In the title compound, C14H20O5, an inter-mediate in the synthesis of
      oligosaccharides, the glycosidic [H-C-O-C(H3)] torsion angle phiH is 52.3 degrees
      and the exo-cyclic [H-C-O-C(H2)] torsion angle thetaH is -11.7 degrees . The
      hexa-pyran-ose ring has a chair conformation. In the crystal, mol-ecules are
      linked by O-H?O hydrogen bonds, forming chains propagating along [010]. Enclosed
      within the chains are R 3 (3)(12) ring motifs involving three mol-ecules. The
      chains are linked via C-H?pi inter-actions, forming a three-dimensional network. 

PMID- 24860369
TI  - 1-(2,3,4,5,6-Penta-methyl-benz-yl)-2-(pyridin-2-yl)-1H-benzimidazole.
AB  - In the title compound, C24H25N3, the benzimidazole ring system is essentially
      planar, with an r.m.s. deviation of 0.017 A, and forms dihedral angles of 7.81
      (5) and 87.61 (4) degrees  with the pyridine and benzene rings, respectively. An
      intra-molecular C-H?N hydrogen bond is observed. In the crystal, mol-ecules are
      stacked along the a axis by weak C-H?pi inter-actions. 

PMID- 24860370
TI  - (E)-4-Methyl-N'-[(4-oxo-4H-chromen-3-yl)methyl-idene]benzohydrazide.
AB  - In the title chromone-tethered benzohydrazide derivative, C18H14N2O3, the 4H
      chromen-4-one and the -CH=N-NH-CO- units are each essentially planar, with the
      largest deviations from thei planes being 0.052 (2) and 0.003 (2) A,
      respectively. The dihedral angles between the 4H-chromen-4-one and the -CH=N-NH
      CO- units, the 4H-chromen-4-one unit and the benzene ring of the 4-tolyl group,
      and the benzene ring of the 4-tolyl group and the -CH=N-NH-CO- unit are 8.09 (7),
      9.94 (5) and 17.97 (8) degrees , respectively. In the crystal, the mol-ecules
      form two types of centrosymmetric dimers: one by N-H?O hydrogen bonds and the
      other by pi-pi stacking inter-actions between the 4H-chromen-4-one unit and the 4
      tolyl group [centroid-centroid distance = 3.641 (5) A]. These dimers form one
      dimensional assemblies extending along the a-axis direction. Additional pi-pi
      stacking inter-actions between two 4H-chromen-4-one units [centroid-centroid
      distance = 3.591 (5) A] and two 4-tolyl groups [centroid-centroid distance =
      3.792 (5) A] organize the mol-ecules into a three-dimensional network. 

PMID- 24860371
TI  - 3-(2-Fluoro-phenyl-sulfon-yl)-2,5,7-trimethyl-1-benzo-furan.
AB  - In the title compound, C17H15FO3S, the dihedral angle between the mean planes of
      the benzo-furan and 2-fluoro-phenyl rings is 87.61 (4) A. In the crystal, mol
      ecules are linked via pairs of C-H?pi inter-actions into inversion-related
      dimers. These dimers are linked by C-H?O hydrogen bonds into supra-molecular
      chains running along the a-axis direction. 

PMID- 24860372
TI  - 5-Bromo-2,7-dimethyl-3-(3-methyl-phenyl-sulfon-yl)-1-benzo-furan.
AB  - In the title compound, C17H15BrO3S, the dihedral angle between the mean planes of
      the benzo-furan and 3-methyl-phenyl rings is 77.37 (5) degrees . In the crystal,
      mol-ecules are linked via pairs of Br?O [Br?O = 3.335 (2) A] contacts into
      inversion dimers. These dimers are further linked by C-H?O hydrogen bonds and pi
      pi inter-actions between the benzene and furan rings of neighbouring mol-ecules
      [centroid-centroid separation = 3.884 (3) A] into supra-molecular chains running
      along the a-axis direction. 

PMID- 24860373
TI  - 5-Chloro-2,7-dimethyl-3-(3-methyl-phenyl-sulfon-yl)-1-benzo-furan.
AB  - In the title compound, C17H15ClO3S, the dihedral angle between the mean planes of
      the benzo-furan and 3-methyl-phenyl rings is 76.99 (4) degrees . In the crystal,
      mol-ecules are linked by C-H?O hydrogen bonds into chains along the b-axis
      direction. These chains are linked by pi-pi inter-actions between the benzene and
      furan rings of neighbouring mol-ecules [centroid-centroid distance = 3.976 (2)
      A]. 

PMID- 24860374
TI  - beta-d-Gulose.
AB  - The title compound, C6H12O6, a C-3 position epimer of d-galactose, crystallized
      from an aqueous solution, was confirmed as beta-d-pyran-ose with a (4) C 1 (C1)
      conformation. In the crystal, O-H?O hydrogen bonds between the hy-droxy groups at
      the C-1 and C-6 positions connect mol-ecules into a tape structure with an R 3
      (3)(11) ring motif running along the a-axis direction. The tapes are connected by
      further O-H?O hydrogen bonds, forming a three-dimensional network. 

PMID- 24860375
TI  - N-[Eth-yl(2-hy-droxy-eth-yl)carbamo-thio-yl]-3-fluoro-benzamide.
AB  - In the title compound, C12H15FN2O2S, the mol-ecule adopts a cis configuration of
      the fluoro-benzoyl group with respect to the thiono group about their C-N bond.
      The dihedral angle between the fluoro-benzoyl group and the thio-urea N2CS
      fragment is 69.60 (11) degrees . An intra-molecular N-H?O hydrogen bond occurs.
      In the crystal, mol-ecules form chains along the b-axis direction via O-H?S and C
      H?O hydrogen bonds. 

PMID- 24860376
TI  - Dopaminium nitrate.
AB  - THE ASYMMETRIC UNIT OF THE TITLE SALT [SYSTEMATIC NAME: 2-(3,4-di-hydroxy-phen
      yl)ethanaminium nitrate], C8H12NO2 (+).NO3 (-), contains two independent cations
      and two independent nitrate anions. The crystal structure consists of discrete
      nitrate ions stacked in layers parallel to (010). These layers are linked via the
      dopaminium cations by O-H?O, N-H?O and weak C-H?O hydrogen bonds, forming a three
      dimensional supra-molecular network. 

PMID- 24860377
TI  - 1,10-Phenanthroline-5,6-dione ethanol monosolvate.
AB  - In the title compound, C12H6N2O2.C2H5OH, the mol-ecule of the 1,10-phenanthroline
      5,6-dione is approximately planar, with a maximum deviation of 0.051 (1) A. In
      the crystal, mol-ecules are linked by O-H?N and weak C-H?O hydrogen bonds,
      forming supra-molecular chains propagating along [110]. pi-pi stacking inter
      actions are observed between the pyridine rings of neighbouring chains, the
      centroid-centroid separations being 3.6226 (11) and 3.7543 (11) A. 

PMID- 24860378
TI  - 4-[(5-Chloro-2-hy-droxy-benzyl-idene)amino]-3-ethyl-1H-1,2,4-triazole-5(4H)
      thione.
AB  - The title compound, C11H11ClN4OS, crystallizes with two mol-ecules, A and B, in
      the asymmetric unit in which the dihedral angles between the triazole and benzene
      rings are 54.6 (3) and 56.0 (3) degrees . Both mol-ecules feature an intra
      molecular O-H?N hydrogen bond, which generates an S(6) ring. In the crystal, A-B
      dimers are linked by pairs of weak C-H?S hydrogen bonds along with pi-pi stacking
      inter-actions between the triazole rings [centroid-centroid separations = 3.631
      (3) and 3.981 (4)A]. N-H?S hydrogen bonds link the dimers into [100] chains,
      which feature R 2 (2)(8) loops. 

PMID- 24860379
TI  - (Z)-1-Di-phenyl-methyl-4-(3-phenyl-prop-2-en-yl)piperazine.
AB  - In the title compound, C26H28N2, the piperazine group adopts a chair conformation
      with the exocyclic N-C bonds in equatorial orientations. The dihedral angle
      between the geminal benzene rings is 80.46 (12) degrees  and the C=C-C-N torsion
      angle is 145.9 (2) degrees . In the crystal, weak C-H?pi inter-actions link the
      mol-ecules into [100] chains. 

PMID- 24860381
TI  - 4-(4-Bromo-phen-yl)-7,7-dimethyl-2-methyl-amino-3-nitro-7,8-di-hydro-4H-chromen
      5(6H)-one including an unknown solvate.
AB  - In the title compound, C18H19BrN2O4, the chromene unit is not quite planar
      (r.m.s. deviation = 0.199 A), with the methyl C atoms lying 0.027 (4) and 1.929
      (4) A from the mean plane of the chromene unit. The six-membered carbocyclic ring
      of the chromene moiety adopts an envelope conformation, with the dimethyl
      substituted C atom as the flap. The methyl-amine and nitro groups are slightly
      twisted from the chromene moiety, with C-N-C-O and O-N-C-C torsion angles of 2.7
      (4) and -0.4 (4) degrees , respectively. The dihedral angle between the mean
      plane of the chromene unit and the benzene ring is 85.61 (13) degrees . An intra
      molecular N-H?O hydrogen bond generates an S(6) ring motif, which stabilizes the
      mol-ecular conformation. In the crystal, mol-ecules are linked via N-H?O hydrogen
      bonds, forming hexa-gonal rings lying parallel to the ab plane. A region of
      disordered electron density, most probably disordered ethanol solvent mol-ecules,
      occupying voids of ca 432 A(3) for an electron count of 158, was treated using
      the SQUEEZE routine in PLATON [Spek (2009 ?). Acta Cryst. D65, 148-155]. Their
      formula mass and unit-cell characteristics were not taken into account during
      refinement. 

PMID- 24860380
TI  - 2-[2,6-Bis(pyrazin-2-yl)pyridin-4-yl]benzoic acid.
AB  - In the title compound, C20H13N5O2, the two pyrazine rings are nearly coplanar
      with the central pyridine ring, forming dihedral angles of 2.21 (9) and 4.57 (9)
      degrees . In contrast, the strong steric hindrance caused by the ortho-carboxyl
      group on the phenyl ring makes this ring rotate out of the attached pyridine ring
      plane by 52.60 (9) degrees . The carboxyl group is twisted from the phenyl ring
      by 22.6 (1) degrees . In the crystal, aromatic pi-pi stacking inter-actions
      [centroid-centroid distances = 3.9186 (4) and 3.9794 (5) A] occur between the
      anti-parallel mol-ecules, generating infinite chains along [100]. O-H?O hydrogen
      bonds connect the chains, leading to the formation of a two-dimensional supra
      molecular network parallel to (010). Inter-molecular C-H?N hydrogen bonds are
      also observed. 

PMID- 24860382
TI  - {2-[(2-Bromo-5-meth-oxy-benzyl-idene)amino]-4,5,6,7-tetra-hydro-benzo[b]thiophen
      3-yl}(phen-yl)methanone.
AB  - In the title compound, C23H20BrNO2S, disorder was modeled for the outer two C
      atoms of the cyclo-hexene ring over two sets of sites with an occupancy ratio of
      0.580 (11):0.420 (11). Both rings have a half-chair conformation. The dihedral
      angles between the mean plane of the thio-phene ring and the benzene and phenyl
      rings are 9.2 (2) and 66.1 (2) degrees , respectively. The benzene and phenyl
      rings are inclined to each other by 74.8 (8) degrees . In the crystal, mol-ecules
      are linked by pairs of C-H?O hydrogen bonds, forming inversion dimers. 

PMID- 24860383
TI  - 6-Fluoro-4-oxo-4H-chromene-3-carbalde-hyde.
AB  - In the title compound, C10H5FO3, the non-H atoms are essentially coplanar (r.m.s.
      deviation = 0.0071 A), with the largest deviation from the mean plane [0.0203
      (15) A] being found for the ring C atom in the 2-position. In the crystal, mol
      ecules are linked into a three-dimensional architecture via C-H?O hydrogen bonds
      and pi-pi stacking inter-actions between the chromone units along the a-axis
      direction [centroid-centroid distance between the benzene and pyran rings = 3.707
      (2) A]. 

PMID- 24860384
TI  - O-Ethyl S-{(S)-1-oxo-1-[(R)-2-oxo-4-phenyl-oxazolidin-3-yl]propan-2-yl} carbonodi
      thio-ate.
AB  - In the title compound, C15H17NO4S2, synthesized by addition of O-ethylxanthic
      acid potassium salt to a diastereomeric mixture of (4R)-3-(2-chloro-propano-yl)-4
      phenyl-oxazolidin-2-one, the oxazolidinone ring has a twist conformation on the C
      C bond. The phenyl ring is inclined to the mean plane of the oxazolidinone ring
      by 76.4 (3) degrees . In the chain the methine H atom is involved in a C-H?S and
      a C-H?O intra-molecular inter-action. In the crystal, mol-ecules are linked by C
      H?pi inter-actions, forming chains along [001]. The S configuration at the C atom
      to which the xanthate group is attached was determined by comparison to the known
      R configuration of the C atom to which the phenyl group is attached. 

PMID- 24860385
TI  - N,N'-(Ethane-1,2-di-yl)di-benzene-carbo-thio-amide.
AB  - The title compound, C16H16N2S2, adopts a gauche (+)-gauche (+)-gauche (+)
      (g(+)g(+)g(+) ) conformation in the NH-CH2-CH2-NH bond sequence. In the crystal,
      mol-ecules are connected by pairs of N-H?S=C hydrogen bonds and C-H?pi inter
      actions, forming a tape structure along the c-axis direction. 

PMID- 24860386
TI  - Ethyl 2-amino-4-(3-nitro-phen-yl)-4H-1-benzothieno[3,2-b]pyran-3-carboxyl-ate.
AB  - The mol-ecule of the title compound, C20H16N2O5S, is built up by one fused five
      membered and two fused six-membered rings linked to eth-oxy-carbonyl and 3-nitro
      phenyl groups. The benzothieno-pyran ring system is nearly planar (r.m.s
      deviation = 0.0392 A) and forms a dihedral angle of 86.90 (6) degrees  with the
      aromatic ring of the nitro-benzene group. In the crystal, mol-ecules are linked
      by N-H?O hydrogen bonds and by pi-pi inter-actions between the phenyl ring and
      the six-membered heterocyle [inter-centroid distance = 3.5819 (8) A], forming a
      three-dimensional network. 

PMID- 24860387
TI  - 1-[(1-Benzyl-1H-1,2,3-triazol-4-yl)meth-yl]indoline-2,3-dione.
AB  - In the title compound, C18H14N4O2, the triazole ring makes dihedral angles of
      77.32 (8) and 75.56 (9) degrees , respectively, with the indoline residue and the
      terminal phenyl group. In the crystal, mol-ecules are linked by C-H?N hydrogen
      bonds into tapes parallel to the b axis. The tapes are linked together by pi-pi
      inter-actions between triazole rings [inter--centroid distance = 3.4945 (9) A]. 

PMID- 24860388
TI  - (1E,4E)-1,5-Bis[4-(di-ethyl-amino)-phen-yl]penta-1,4-dien-3-one.
AB  - There are two crystallograpically independent mol-ecules in the asymmetric unit
      of the title bis-chalcone derivative, C25H32N2O. Both mol-ecules are twisted with
      a dihedral angle between the two substituted benzene rings of 11.19 (16) degrees 
      in one mol-ecule and 14.40 (15) degrees  in the other. The central penta-1,4-dien
      3-one fragments make dihedral angles of 8.49 (17) and 4.26 (17) degrees  with the
      two adjacent benzene rings in one mol-ecule, whereas the corresponding values are
      8.42 (16) and 6.18 (16) degrees  in the other. In the crystal, mol-ecules are
      arranged into chains along the c-axis direction. Adjacent chains are inter-linked
      by weak inter-molecular C-H?O inter-actions. The crystal is further stabilized by
      C-H?pi inter-actions. 

PMID- 24860389
TI  - (2E)-2-Benzyl-idene-N-phenyl-hydrazinecarboxamide.
AB  - The mol-ecule of the title compound, C14H13N3O, adopts an E conformation with
      respect to the azomethine C=N bond, and is roughly planar, with an r.m.s.
      deviation of the non-H atoms from the least-squares plane of 0.100 (2) A and a
      dihedral angle between the terminal benzene rings of 5.74 (12) degrees . An
      intramolecular N-H?N hydrogen bond closes an S(6) ring. In the crystal, mol
      ecules are linked by the pairs of N-H?O hydrogen bonds into centrosymmetric
      dimers. Dimers related by translation along [010] form slanted stacks, the
      shortest C?C inter-molecular distance within the stack being 3.283 (3) A. Weak C
      H?pi inter-actions link the stacks into a three-dimensional structure. 

PMID- 24860390
TI  - 5-Cyclo-pentyl-2-methyl-3-(4-methyl-phenyl-sulfon-yl)-1-benzo-furan.
AB  - In the title compound, C21H22O3S, the cyclo-pentyl ring adopts a twist
      conformation. The dihedral angle between the mean planes of the benzo-furan and 4
      methyl-phenyl rings is 72.38 (6) degrees . In the crystal, mol-ecules are linked
      by C-H?O and C-H?pi inter-actions, forming a three-dimensional supra-molecular
      network. 

PMID- 24860391
TI  - (E)-3-(4-Hy-droxy-3-meth-oxy-phen-yl)-1-(4-hy-droxy-phen-yl)prop-2-en-1-one.
AB  - In the title compound, C16H14O4, there is an intra-molecular O-H?O hydrogen bond.
      The benzene rings are inclined to one another by 13.89 (9) degrees . The prop-2
      en-1-one group is twisted slightly, the O=C-Car-Car (ar = aromatic) and C=C-C=O
      torsion angles being -10.4 (3) and -7.4 (3) degrees , respectively. In the
      crystal, mol-ecules are linked by O-H?O hydrogen bonds, forming chains along
      [100]. These chains are further linked by O-H?O hydrogen bonds, forming
      corrugated sheets lying parallel to (010). There are C-H?pi inter-actions present
      within the sheets. 

PMID- 24860392
TI  - (1S,2R,3S,6S,7R)-3,7,11,11-Tetra-methyl-6,7-epoxybi-cyclo-[5.4.0]undecane-2-ol.
AB  - The title compound, C15H26O2, was synthesized from beta-himachalene (3,5,5,9
      tetra-methyl-2,4a,5,6,7,8-hexa-hydro-1H-benzo-cyclo-heptene), which was isolated
      from the Atlas cedar (cedrus atlantica). The mol-ecule is built up from a seven
      membered ring to which a six- and a three-membered ring are fused. The seven- and
      six-membered rings each have a twist-boat conformation. In the crystal, O-H?O
      hydrogen bonds link the mol-ecules into zigzag chains running along the b-axis
      direction. 

PMID- 24860393
TI  - 3-Bromo-2-[4-(methyl-sulfan-yl)phen-yl]-5,6,7,8-tetra-hydro-1,3-benzo-thia
      zolo[3,2-a]imidazole.
AB  - In the title mol-ecule, C16H15BrN2S2, the central imidazo[2,1-b]thia-zole
      fragment is almost planar (r.m.s. deviation = 0.012 A), and the fused 5,6,7,8
      tetra-hydro-benzene ring adopts an unsymmetrical half-chair conformation. The
      dihedral angle between the imidazo[2,1-b]thia-zole and benzene planes is 18.25
      (4) degrees . The terminal methyl-sulfanyl substituent lies practically within
      the benzene plane [the dihedral angle between the corresponding planes is 7.20
      (10) degrees ] and is turned toward the C-Br bond. In the crystal, mol-ecules
      form infinite chains along [100] via secondary Br?N inter-actions [3.1861 (16)
      A]. The chains are arranged at van der Waals distances. 

PMID- 24860394
TI  - (E)-2-{[4-(Di-methyl-amino)-benzyl-idene]amino}-5-nitro-phenol.
AB  - The title Schiff base compound, C15H15N3O3, crystallizes with two mol-ecules (A
      and B) in the asymmetric unit. Each mol-ecule adopts an E conformation around the
      C= N imine bond. The two mol-ecules have minor differences in their
      conformations. In mol-ecule A, the dihedral angle between the nitro group and its
      benzene ring is 2.1 (2) degrees  and that between the two benzene rings is 0.88
      (7) degrees , while the corresponding angles for mol-ecule B are 5.7 (1) and 2.45
      (6) degrees , respectively. In each mol-ecule, there is an intra-molecular O-H?N
      hydrogen bond. In the crystal, inversion-related mol-ecules are linked via O-H?O
      hydrogen bonds forming A-A and B-B dimers. These dimers are linked via C-H?O
      hydrogen bonds involving the nitro O atoms, forming A-A-A and B-B-B slabs that
      lie parallel to one another and to (010). 

PMID- 24860395
TI  - 2-Amino-6-methyl-pyridinium 4-methyl-benzene-sulfonate.
AB  - In the asymmetric unit of the title salt, C6H9N2 (+).C7H7O3S(-), there are two
      independent 2-amino-6-methyl-pyridinium cations and two independent 4-methyl
      benzene-sulfonate anions. Both cations are protonated at their pyridine N atoms
      and their geometries reveal amine-imine tautomerism. In the 4-methyl-benzene
      sulfonate anions, the carboxyl-ate groups are twisted out of the benzene ring
      planes by 88.4 (1) and 86.2 (2) degrees . In the crystal, the sulfonate O atoms
      of an anion inter-act with the protonated N atoms and the 2-amino groups of a
      cation via a pair of N-H?O hydrogen bonds, forming an R 2 (2)(8) ring motif.
      These motifs are connected via N-H?O hydrogen bonds, forming chains running along
      the a-axis direction. Within the chains there are weak C-H?O hydrogen bonds
      present. In addition, aromatic pi-pi stacking inter-actions [centroid-centroid
      distances = 3.771 (2), 3.599 (2), 3.599 (2) and 3.497 (2) A] involving
      neighbouring chains are also observed. 

PMID- 24860396
TI  - N-[Eth-yl(2-hy-droxy-eth-yl)carbamo-thio-yl]-2-methyl-benzamide.
AB  - The title compound, C13H18N2O2S, adopts a cis conformation between the methyl
      benzoyl and thiono groups across their thio-urea C-N bond. However, the methyl
      benzoyl group and N2CS thio-urea moiety are twisted by 15.03 (3) degrees . In the
      molecule there is an N-H?O hydrogen bond. In the crystal, mol-ecules are linked
      by O-H?O inter-actions, generating chains extending along the c-axis direction. 

PMID- 24860397
TI  - (E)-4-Chloro-2-{[4-(di-methyl-amino)-benzyl-idene]amino}-phenol.
AB  - In the title aromatic Schiff base compound, C15H15ClN2O, the mol-ecule exists in
      a trans conformation with respect to the C=N bond. The dihedral angle between the
      benzene rings is 14.49 (6) degrees . In the crystal, weak C-H?pi inter-actions
      link mol-ecules into supra-molecular chains propagated along the a-axis
      direction. 

PMID- 24860398
TI  - 5-Amino-6-benzoyl-8-nitro-2,3-di-hydro-1H-spiro-[imidazo[1,2-a]pyridine-7,3'
      indolin]-2'-one dimethyl sulfoxide monosolvate.
AB  - In the title compound C21H17N5O4.C2H6OS, the central six-membered ring derived
      from 1,4-di-hydro-pyridine adopts a distorted boat conformation with a small
      puckering amplitude of 0.127 (3) A. The sums of bond angles around the pyridine N
      atom [358.7 (2) degrees ] and the other imidazolidine N atom [60 (2) degrees ]
      indicate that these atoms are in sp(2) hybridization, leading to an essentially
      planar imidazolidine ring. The last heterocycle, an oxindole moiety, is also
      nearly planar with an r.m.s. deviation of 0.0185 (1) A. The amine NH2 group forms
      an intra-molecular hydrogen bond with the benzoyl group, giving a S(6) motif. In
      the crystal, N-H?O hydrogen bonds lead to the formation of chains along the c
      axis direction. Within the chains there are further N-H?O and C-H?O hydrogen
      bonds enclosing R (2) 2(14) ring motifs. The chains are linked via N-H?O and C
      H?O hydrogen bonds involving the dimethyl sulfoxide solvent mol-ecule which acts
      as both an acceptor and a donor.. 

PMID- 24860399
TI  - (R)-[(R)-3-Benzyl-2-oxooxazolidin-4-yl][4-(methyl-sulfon-yl)phen-yl]methyl
      acetate.
AB  - The structure of the title compound, C20H21NO6S, is of inter-est with respect to
      its anti-bacterial properties. The oxazolidine ring makes dihedral angles of
      79.63 (14) and 56.16 (12) degrees  with the phenyl and benzene rings,
      respectively, while the phenyl and benzene rings make a dihedral angle of 64.37
      (13) degrees . In the crystal, non-classical C-H?O hydrogen bonds link adjacent
      mol-ecules along the c axis. 

PMID- 24860400
TI  - 2,4-Di-chloro-1-iodo-6-nitro-benzene.
AB  - In the crystal structure of the title compound, C6H2Cl2INO2, there are weak C
      H?Cl inter-actions and I?O [3.387 (4) A] close contacts. These inter-actions form
      sheets in the ac plane, with the closest contact between adjacent planes
      occurring between inversion-related nitro O atoms [3.025 (8) A]. The molecule
      possesses mirror symmetry, with the halogen, N and C atoms all lying in the
      mirror plane. Hence, the dihedral angle between the benzene ring and the nitro
      group is 90 degrees . 

PMID- 24860401
TI  - (2E)-1-(3,5-Di-hydroxy-phen-yl)-3-(4-meth-oxy-phen-yl)prop-2-en-1-one.
AB  - In the title compound, C16H14O4, the benzene rings are inclined to one another by
      4.91 (7) degrees . The conformation about the C=O and C=C bonds is trans and cis,
      respectively. In the crystal, mol-ecules are linked by O-H?O hydrogen bonds,
      forming inversion dimers with an R 2 (2)(14) ring motif. The dimers are linked
      via O-H?O and C-H?O hydrogen bonds, forming undulating two-dimensional networks
      lying parallel to (10-1). These networks are linked by further C-H?O hydrogen
      bonds, forming a three-dimensional structure. 

PMID- 24860402
TI  - 1-(4-Bromo-benz-yl)-2-(4-bromo-phen-yl)-1H-benzimidazole.
AB  - There are two mol-ecules in the asymmetric unit of the title compound,
      C20H14Br2N2. In the first, the dihedral angles between the mean plane of the
      benzimidazole group and those of the 4-bromo-benzyl and 4-chloro-phenyl groups
      are 50.72 (17) and 71.29 (16) degrees , respectively, while the corresponding
      angles in the second mol-ecule are 42.09 (16) and 89.05 (17) degrees . The 4
      bromo-benzyl and 4-bromo-phenyl groups make an angle of 68.1 (2) and 85.1 (21)
      degrees  with each other in the two mol-ecules. In the crystal, weak C-H?N and C
      H?Br hydrogen bonds link the mol-ecules along the c-axis direction. Br?Br inter
      actions [3.5733 (9)A] are also observed. 

PMID- 24860403
TI  - 4-Chloro-N'-[(E)-2-chloro-benzyl-idene]benzohydrazide monohydrate.
AB  - The title compound, C14H10Cl2N2O.H2O, has a nearly planar extended conformation
      [C-N-N-C = -173.66 (15) degrees ]. The dihedral angle between the aromatic rings
      is 4.6 (2) degrees . The water mol-ecules alternate with benzohydrazide mol
      ecules in chains formed by O-H?O hydrogen bonds which run parallel to the a axis.
      These chains are linked to neighboring chains through N-H?O and C-H?O inter
      actions, forming a layer parallel to (001). 

PMID- 24860404
TI  - N-(2-Nitro-phen-yl)thio-phene-2-carbox-amide.
AB  - The title compound, C11H8N2O3S, shows two mol-ecules per asymmetric unit, with
      the dihedral angles between the benzene and thio-phene rings of 13.53 (6) and
      8.50 (5) degrees  being a notable difference between them. An intra-molecular N
      H?O hydrogen-bond in each mol-ecule generates an S(6) ring motif. The crystal
      packing shows no classical hydrogen bonds with the mol-ecules being packed to
      form weak C-H?O and C-H?S inter-actions leading to R 2 (2)(9) and R 4 (4)(25)
      rings which are edge-shared, giving layers parallel to (010). 

PMID- 24860405
TI  - (2Z)-2-Benzyl-idene-4-(prop-2-yn-1-yl)-2H-1,4-benzo-thia-zin-3(4H)-one.
AB  - The mol-ecule of the title compound, C18H13NOS, is build up from two fused six
      membered rings, with the heterocyclic component linked to a benzyl-idene group
      and to a prop-2-yn-1-yl chain. The six-membered heterocycle adopts a distorted
      screw-boat conformation. The prop-2-yn-1-yl chain is almost perpendicular to the
      mean plane through benzo-thia-zine as indicated by the C-N-C-C torsion angle of
      86.5 (2) degrees . The dihedral angle between the benzene rings is 47.53 (12)
      degrees . There are no specific inter-molecular inter-actions in the crystal
      packing. 

PMID- 24860406
TI  - 4,4'-Dimeth-oxybi-phenyl-3,3'-di-car-box-ylic acid.
AB  - The title compound, C16H14O6, was recrystallized under solvothermal conditions.
      The mol-ecules are located on inversion centres, with one complete mol-ecule
      generated from the asymmetric unit by inversion. There are intra-molecular O-H?O
      hydrogen bonds involving the carb-oxy-lic acid group and the O atom of the
      adjacent meth-oxy group. In the crystal, mol-ecules are linked via O-H?O hydrogen
      bonds, forming chains propagating along [100]. The chains are linked via C-H?O
      hydrogen bonds, forming sheets parallel to (001). 

PMID- 24860407
TI  - 2-Nitro-benzyl methane-sulfonate.
AB  - In the title compound, C8H9NO5S, the dihedral angle between the benzene ring and
      the nitro group is 5.86 (15) degrees  and the C-C-O-S group adopts an anti
      conformation [torsion angle = -168.44 (15) degrees ]. In the crystal, mol-ecules
      are linked by C-H?O hydrogen bonds, generating a three-dimensional network. 

PMID- 24860408
TI  - 1,6-Bis(p-tol-yloxy)hexa-ne.
AB  - The title compound, C20H26O2, crystallized with one half-mol-ecule in the
      asymmetric unit. The whole mol-ecule is generated by inversion symmetry, with the
      center of inversion being situated at the mid-point of the central -CH2-CH2- bond
      of the bridging hexane chain. In the crystal, mol-ecules stack in columns along
      the b axis. C-H?pi inter-actions are present within the columns. 

PMID- 24860409
TI  - Tri-benzyl-ammonium chloride.
AB  - Single crystals of the title salt, C21H21NH(+).Cl(-), were isolated as a side
      product from the reaction involving [(C6H5CH2)3NH]2[HPO4] and Sn(CH3)3Cl in
      ethanol. Both the cation and the anion are situated on a threefold rotation axis.
      The central N atom in the cation has a slightly distorted tetra-hedral
      environment, with angles ranging from 107.7 to 111.16 (10) degrees . In the
      crystal, the tri-benzyl-ammonium cations and chloride anions are linked through N
      H?Cl and C-H?Cl hydrogen bonds, leading to the formation of infinite chains along
      [001]. The crystal studied was a merohedral twin. 

PMID- 24860410
TI  - 6-Cyanona-phthalen-2-yl 4-hexyl-benzo-ate.
AB  - In the title compound, C24H23NO2, a whole mol-ecule is disordered over two sets
      of sites with occupancies in a ratio of 0.692 (6):0.308 (6). In the major
      disorder component, the naphthalene ring system forms a dihedral angle of 68.6
      (5) degrees  with the benzene ring. The corresponding angle in the minor
      component is 81.6 (10) degrees . In the crystal, mol-ecules are linked into
      chains propagating along the b-axis direction via weak C-H?O hydrogen bonds. The
      crystal packing is further consolidated by weak C-H?pi inter-actions. 

PMID- 24860411
TI  - 2-[2-(2-Nitro-phen-yl)-4,5-diphenyl-1H-imidazol-1-yl]-3-phenyl-propan-1-ol.
AB  - In the title compound, C30H25N3O3, the central imidazole ring forms dihedral
      angles of 77.34 (6), 12.56 (6) and 87.04 (6) degrees , respectively, with the o
      nitro-benzene ring and the phenyl substituents in the 5- and 4-positions. The mol
      ecular conformation is stabilized by weak intra-molecular C-H?pi inter-actions.
      In the crystal, mol-ecules are linked by O-H?N hydrogen bonds, forming chains
      running parallel to the b-axis direction. 

PMID- 24860412
TI  - 3-[(4-Phen-oxy-phen-yl)sulfan-yl]-5-phenyl-1H-1,2,4-triazole.
AB  - The title compound, C20H15N3OS, is V-shaped. In the 4-phen-oxy-phenyl group, the
      two rings are inclined to one another by 74.52 (13) degrees . These rings are
      inclined to the triazole ring by 72.20 (15) and 72.30 (15) degrees ,
      respectively. The phenyl ring is inclined to the triazole ring by 10.85 (12)
      degrees . In the crystal, mol-ecules are linked via N-H?N hydrogen bonds, forming
      chains propagating along [010]. These chains are linked via pairs of C-H?S
      hydrogen bonds, forming sheets lying parallel to the ac plane. 

PMID- 24860413
TI  - N-(2-Allyl-4-eth-oxy-2H-indazol-5-yl)-4-methyl-benzene-sulfonamide.
AB  - The indazole ring system of the title compound, C19H21N3O3S, is almost planar
      (r.m.s. deviation = 0.0192 A) and forms dihedral angles of 77.99 (15) and 83.9
      (3) degrees  with the benzene ring and allyl group, respectively. In the crystal,
      centrosymmetrically related mol-ecules are connected by pairs of N-H?O hydrogen
      bonds into dimers, which are further linked by C-H?O hydrogen bonds, forming
      columns parallel to the b axis. 

PMID- 24860414
TI  - Four-layered [3.3]meta-cyclo-phane with ethene-tetra-carbo-nitrile.
AB  - The title complex C42H48.2C6N4 {systematic name: hepta
      cyclo[21.13.1.1(5,19).1(6,18).1(10,14).1(24,36).1(28,32)]do-tetra-conta
      1(37),5(40),6(41),10(42),11,13,18,23,28,30,32(39),36(38)-dodeca-ene-ethene-tetra
      carbo-nitrile (1/2)}, consisting of four-layered [3.3]meta-cyclo-phane (MCP) with
      two tetra-cyano-ethyl-ene (TCNE) mol-ecules, was grown from a mixture of MCP and
      TCNE in chloro-form solution. The four-layered [3.3]MCP has an S-shaped structure
      in which three [3.3]MCP moieties take syn-(chair-boat), anti-(chair-boat) and syn
      (chair-boat) conformations. The two outer [3.3]MCP moieties with syn geometry
      contain benzene rings with a tilt of 32.95 (7) degrees . The central [3.3]MCP
      moiety has an anti geometry, in which the two benzene rings are oriented parallel
      to each other at a transannular distance of 2.31 A. The TCNE mol-ecules are
      stacked on either side of the outer [3.3]MCP units at a distance of 3.19 A on one
      side and 3.24 A on the other, and showed 0.80:0.20 and 0.44:0.56 disorder,
      respectively. 

PMID- 24860415
TI  - Subthalamic nucleus stimulation does not influence basal glucose metabolism or
      insulin sensitivity in patients with Parkinson's disease.
AB  - Animal studies have shown that central dopamine signaling influences glucose
      metabolism. As a first step to show this association in an experimental setting
      in humans, we studied whether deep brain stimulation (DBS) of the subthalamic
      nucleus (STN), which modulates the basal ganglia circuitry, alters basal
      endogenous glucose production (EGP) or insulin sensitivity in patients with
      Parkinson's disease (PD). We studied 8 patients with PD treated with DBS STN, in
      the basal state and during a hyperinsulinemic euglycemic clamp using a stable
      glucose isotope, in the stimulated and non-stimulated condition. We measured EGP,
      hepatic insulin sensitivity, peripheral insulin sensitivity (Rd), resting energy
      expenditure (REE), glucoregulatory hormones, and Parkinson symptoms, using the
      Unified Parkinson's Disease Rating Scale (UPDRS). Basal plasma glucose and EGP
      did not differ between the stimulated and non-stimulated condition. Hepatic
      insulin sensitivity was similar in both conditions and there were no significant
      differences in Rd and plasma glucoregulatory hormones between DBS on and DBS off.
      UPDRS was significantly higher in the non-stimulated condition. DBS of the STN in
      patients with PD does not influence basal EGP or insulin sensitivity. These
      results suggest that acute modulation of the motor basal ganglia circuitry does
      not affect glucose metabolism in humans. 

PMID- 24860417
TI  - Hearing in action; auditory properties of neurons in the red nucleus of alert
      primates.
AB  - The response of neurons in the Red Nucleus pars magnocellularis (RNm) to both
      tone bursts and electrical stimulation were observed in three cynomolgus monkeys
      (Macaca fascicularis), in a series of studies primarily designed to characterize
      the influence of the dopaminergic ventral midbrain on auditory processing.
      Compared to its role in motor behavior, little is known about the sensory
      response properties of neurons in the red nucleus (RN); particularly those
      concerning the auditory modality. Sites in the RN were recognized by observing
      electrically evoked body movements characteristic for this deep brain structure.
      In this study we applied brief monopolar electrical stimulation to 118 deep brain
      sites at a maximum intensity of 200 MUA, thus evoking minimal body movements.
      Auditory sensitivity of RN neurons was analyzed more thoroughly at 15 sites, with
      the majority exhibiting broad tuning curves and phase locking up to 1.03 kHz.
      Since the RN appears to receive inputs from a very early stage of the ascending
      auditory system, our results suggest that sounds can modify the motor control
      exerted by this brain nucleus. At selected locations, we also tested for the
      presence of functional connections between the RN and the auditory cortex by
      inserting additional microelectrodes into the auditory cortex and investigating
      how action potentials and local field potentials (LFPs) were affected by
      electrical stimulation of the RN. 

PMID- 24860416
TI  - Decoding of the spike timing of primary afferents during voluntary arm movements
      in monkeys.
AB  - Understanding the mechanisms of encoding forelimb kinematics in the activity of
      peripheral afferents is essential for developing a somatosensory neuroprosthesis.
      To investigate whether the spike timing of dorsal root ganglion (DRG) neurons
      could be estimated from the forelimb kinematics of behaving monkeys, we implanted
      two multi-electrode arrays chronically in the DRGs at the level of the cervical
      segments in two monkeys. Neuronal activity during voluntary reach-to-grasp
      movements were recorded simultaneously with the trajectories of hand/arm
      movements, which were tracked in three-dimensional space using a motion capture
      system. Sixteen and 13 neurons, including muscle spindles, skin receptors, and
      tendon organ afferents, were recorded in the two monkeys, respectively. We were
      able to reconstruct forelimb joint kinematics from the temporal firing pattern of
      a subset of DRG neurons using sparse linear regression (SLiR) analysis,
      suggesting that DRG neuronal ensembles encoded information about joint
      kinematics. Furthermore, we estimated the spike timing of the DRG neuronal
      ensembles from joint kinematics using an integrate-and-fire model (IF)
      incorporating the SLiR algorithm. The temporal change of firing frequency of a
      subpopulation of neurons was reconstructed precisely from forelimb kinematics
      using the SLiR. The estimated firing pattern of the DRG neuronal ensembles
      encoded forelimb joint angles and velocities as precisely as the originally
      recorded neuronal activity. These results suggest that a simple model can be used
      to generate an accurate estimate of the spike timing of DRG neuronal ensembles
      from forelimb joint kinematics, and is useful for designing a proprioceptive
      decoder in a brain machine interface. 

PMID- 24860418
TI  - Decreased serotonin transporter immunoreactivity in the human hypothalamic
      infundibular nucleus of overweight subjects.
AB  - CONTEXT: That serotonin plays a role in the regulation of feeding behavior and
      energy metabolism has been known for a long time. Serotonin transporters (SERT)
      play a crucial role in serotonin signaling by regulating its availability in the
      synaptic cleft. The neuroanatomy underlying serotonergic signaling in humans is
      largely unknown, and until now, SERT immunoreactivity in relation to body weight
      has not been investigated. OBJECTIVE: To clarify the distribution of SERT
      immunoreactivity throughout the human hypothalamus and to compare SERT
      immunoreactivity in the infundibular nucleus (IFN), the human equivalent of the
      arcuate nucleus, in lean and overweight subjects. DESIGN: First, we investigated
      the distribution of serotonin transporters (SERT) over the rostro-caudal axis of
      six post-mortem hypothalami by means of immunohistochemistry. Second, we
      estimated SERT immunoreactivity in the IFN of lean and overweight subjects.
      Lastly, double-labeling of SERT with Neuropeptide Y (NPY) and melanocortin cell
      populations was performed to further identify cells showing basket-like SERT
      staining. RESULTS: SERT-immunoreactivity was ubiquitously expressed in fibers
      throughout the hypothalamus and was the strongest in the IFN. Immunoreactivity in
      the IFN was lower in overweight subjects (p = 0.036). Basket-like staining in the
      IFN was highly suggestive of synaptic innervation. A very small minority of cells
      showed SERT double labeling with NPY, agouti-related protein and alpha-melanocyte
      stimulating hormone. CONCLUSIONS: SERT is ubiquitously expressed in the human
      hypothalamus. Strong SERT immunoreactivity, was observed in the IFN a region
      important for appetite regulation, in combination with lower SERT
      immunoreactivity in the IFN of overweight and obese subjects, may point toward a
      role for hypothalamic SERT in human obesity.

PMID- 24860419
TI  - Basis for a neuronal version of Grover's quantum algorithm.
AB  - Grover's quantum (search) algorithm exploits principles of quantum information
      theory and computation to surpass the strong Church-Turing limit governing
      classical computers. The algorithm initializes a search field into superposed N
      (eigen)states to later execute nonclassical "subroutines" involving unitary phase
      shifts of measured states and to produce root-rate or quadratic gain in the
      algorithmic time (O(N (1/2))) needed to find some "target" solution m. Akin to
      this fast technological search algorithm, single eukaryotic cells, such as
      differentiated neurons, perform natural quadratic speed-up in the search for
      appropriate store-operated Ca(2+) response regulation of, among other processes,
      protein and lipid biosynthesis, cell energetics, stress responses, cell fate and
      death, synaptic plasticity, and immunoprotection. Such speed-up in cellular
      decision making results from spatiotemporal dynamics of networked intracellular
      Ca(2+)-induced Ca(2+) release and the search (or signaling) velocity of Ca(2+)
      wave propagation. As chemical processes, such as the duration of Ca(2+)
      mobilization, become rate-limiting over interstore distances, Ca(2+) waves
      quadratically decrease interstore-travel time from slow saltatory to fast
      continuous gradients proportional to the square-root of the classical Ca(2+)
      diffusion coefficient, D (1/2), matching the computing efficiency of Grover's
      quantum algorithm. In this Hypothesis and Theory article, I elaborate on these
      traits using a fire-diffuse-fire model of store-operated cytosolic Ca(2+)
      signaling valid for glutamatergic neurons. Salient model features corresponding
      to Grover's quantum algorithm are parameterized to meet requirements for the
      Oracle Hadamard transform and Grover's iteration. A neuronal version of Grover's
      quantum algorithm figures to benefit signal coincidence detection and
      integration, bidirectional synaptic plasticity, and other vital cell functions by
      rapidly selecting, ordering, and/or counting optional response regulation
      choices. 

PMID- 24860420
TI  - Brain patterning perturbations following PTEN loss.
AB  - This review will consider the impact of compromised PTEN signaling in brain
      patterning. We approach understanding the contribution of PTEN to nervous system
      development by surveying the findings from the numerous genetic loss-of-function
      models that have been generated as well as other forms of PTEN inactivation. By
      exploring the developmental programs influenced by this central transduction
      molecule, we can begin to understand the molecular mechanisms that shape the
      developing brain. A wealth of data indicates that PTEN plays critical roles in a
      variety of stages during brain development. Many of them are considered here
      including: stem cell proliferation, fate determination, polarity, migration,
      process outgrowth, myelination and somatic hypertrophy. In many of these
      contexts, it is clear that PTEN phosphatase activity contributes to the observed
      effects of genetic deletion or depletion, however recent studies have also
      ascribed non-catalytic functions to PTEN in regulating cell function. We also
      explore the potential impact this alternative pool of PTEN may have on the
      developing brain. Together, these elements begin to form a clearer picture of how
      PTEN contributes to the emergence of brain structure and binds form and function
      in the nervous system. 

PMID- 24860422
TI  - Premature lethality, hyperactivity, and aberrant phosphorylation in transgenic
      mice expressing a constitutively active form of Fyn.
AB  - The kinase Fyn, the microtubule-associated protein tau and the peptide amyloid
      beta (Abeta) constitute a toxic triad in Alzheimer's disease (AD). Tau's
      subcellular localization is mainly regulated by phosphorylation whereas Fyn's
      localization is dictated by palmitoylation targeting it to the plasma membrane in
      a reversible manner. We have previously shown that tau is required for Fyn to be
      targeted to the dendritic spine. We had also shown that a truncated form of tau
      (Deltatau) that accumulates in the cell soma is capable of trapping Fyn and
      preventing it from entering the spine. Here we determined that palmitoylation is
      required for Fyn's membrane and spine localization. We further evaluated the
      functional consequences of neuronal over-expression of the constitutively active
      Y531F mutant form of Fyn (FynCA) in transgenic mice. We found that the FynCA
      transgenic mice displayed a reduced weight, a massively reduced lifespan and a
      high level of hyperactivity. The lifespan of the FynCA mice was only slightly
      extended by crossing them with Deltatau transgenic mice, possibly reflecting
      differences in expression patterns of the transgenes and high levels of
      transgenic FynCA compared to endogenous Fyn. Analysis of synaptosomes revealed
      that FynCA accumulated at high levels in the spine, resulting in increased levels
      of the NMDA receptor subunit NR2b phosphorylated at residue Y1472. Tau was
      strongly phosphorylated at the AT8 epitope S202/T205 as shown by Western blot and
      immunohistochemistry indicating that an increased tyrosine kinase activity of Fyn
      has down-stream consequences for serine/threonine-directed phosphorylation. 

PMID- 24860421
TI  - Regulation of neurotrophin receptor (Trk) signaling: suppressor of cytokine
      signaling 2 (SOCS2) is a new player.
AB  - The classic neurotrophins Nerve Growth Factor (NGF), Brain Derived Neurotrophic
      Factor (BDNF) and Neurotrophins NT-3 and NT-4 are well known to regulate various
      aspects of neuronal differentiation, survival and growth. They do this by binding
      to their cognate receptors, members of the Tropomyosin-related kinase (Trk)
      receptor tyrosine kinase family, namely TrkA, TrkB, and TrkC. These receptors are
      then internalized and localized to different cellular compartments, where signal
      transduction occurs. Conversely, members of the suppressor of cytokine signaling
      (SOCS) family are best known as negative regulators of signaling via the JAK/STAT
      pathway. Some members of the family, and in particular SOCS2, have roles in the
      nervous system that at least partially overlap with that of neurotrophins, namely
      neuronal differentiation and neurite outgrowth. Recent evidence suggests that
      SOCS2 is a novel regulator of NGF signaling, altering TrkA cellular localization
      and downstream signaling to affect neurite growth but not neuronal survival. This
      review first discusses regulation of Trk receptor signaling, followed by the role
      of SOCS2 in the nervous system and finishes with a discussion of possible
      mechanisms by which SOCS2 may regulate TrkA function. 

PMID- 24860423
TI  - The role of telocytes in morphogenetic bioelectrical signaling: once more unto
      the breach.

PMID- 24860426
TI  - Alterations of protein composition along the rostro-caudal axis after spinal cord
      injury: proteomic, in vitro and in vivo analyses.
AB  - Based on proteomic analyses we investigated the differences of released molecules
      in the conditioned media (CM) from the spinal cord central lesion and adjacent
      rostral and caudal segments at 3, 7, and 10 days after spinal cord injury (SCI),
      in order to specify the molecular environment within greater extent of tissue
      damage. Proteins found in CM were analyzed by shot-gun MS using nanoLC coupled to
      an orbitrap. The results showed some specific proteins at each site of the lesion
      at 3days. Among the proteins from rostral and lesion segments, some are related
      to chemokines, cytokines or to neurogenesis factors. In contrast, proteins from
      caudal segments are more related to necrosis factors. The CM from each spinal
      segment were used in vitro, on microglial BV2 cell lines and DRGs explants,
      showing a lesion site-dependent impact on microglia activation and DRGs neurite
      outgrowth. In addition, while naive BV2 cells exhibited insignificant staining
      for CX3CR1 receptor, the level of CX3CR1 was strongly enhanced in some BV2 cells
      after their stimulation by CM collected from SCI. The molecular data might
      correlate with different polarization of activated microglia and macrophages
      along the rostro-caudal axis following acute injury. This was partially confirmed
      in vivo with CX3CR1 receptor, revealing higher expression in the rostral segment,
      with potential neuroprotective action. In addition, the neurotrophic factors
      released from rostral and lesion segments enhanced outgrowth of DRGs explants.
      Taken together these data suggest that regionalization in terms of inflammatory
      and neurotrophic responses may occur between rostral and caudal segments in acute
      SCI. 

PMID- 24860425
TI  - Insights gained from gene therapy in animal models of retGC1 deficiency.
AB  - Vertebrate species possess two retinal guanylate cyclases (retGC1 and retGC2) and
      at least two guanylate cyclase activating proteins (GCAPs), GCAP1 and GCAP2.
      GCAPs function as Ca(2+) sensors that regulate the activity of guanylate
      cyclases. Together, these proteins regulate cGMP and Ca(2+) levels within the
      outer segments of rod and cone photoreceptors. Mutations in GUCY2D, the gene that
      encodes retGC1, are a leading cause of the most severe form of early onset
      retinal dystrophy, Leber congenital amaurosis (LCA1). These mutations, which
      reduce or abolish the ability of retGC1 to replenish cGMP in photoreceptors, are
      thought to lead to the biochemical equivalent of chronic light exposure in these
      cells. In spite of this, the majority of LCA1 patients retain normal
      photoreceptor laminar architecture aside from foveal cone outer segment
      abnormalities, suggesting they may be good candidates for gene replacement
      therapy. Work began in the 1980s to characterize multiple animal models of retGC1
      deficiency. 34 years later, all models have been used in proof of concept gene
      replacement studies toward the goal of developing a therapy to treat GUCY2D-LCA1.
      Here we use the results of these studies as well as those of recent clinical
      studies to address specific questions relating to clinical application of a gene
      therapy for treatment of LCA1. 

PMID- 24860427
TI  - Frizzled-9 impairs acetylcholine receptor clustering in skeletal muscle cells.
AB  - Cumulative evidence indicates that Wnt pathways play crucial and diverse roles to
      assemble the neuromuscular junction (NMJ), a peripheral synapse characterized by
      the clustering of acetylcholine receptors (AChR) on postsynaptic densities. The
      molecular determinants of Wnt effects at the NMJ are still to be fully
      elucidated. We report here that the Wnt receptor Frizzled-9 (Fzd9) is expressed
      in developing skeletal muscles during NMJ synaptogenesis. In cultured myotubes,
      gain- and loss-of-function experiments revealed that Fzd9-mediated signaling
      impairs the AChR-clustering activity of agrin, an organizer of postsynaptic
      differentiation. Overexpression of Fzd9 induced the cytosolic accumulation of
      beta-catenin, a key regulator of Wnt signaling. Consistently, Fzd9 and beta
      catenin localize in the postsynaptic domain of embryonic NMJs in vivo. Our
      findings represent the first evidence pointing to a crucial role of a Fzd
      mediated, beta-catenin-dependent signaling on the assembly of the vertebrate NMJ.

PMID- 24860429
TI  - The kinetics of multibranch integration on the dendritic arbor of CA1 pyramidal
      neurons.
AB  - The process by which synaptic inputs separated in time and space are integrated
      by the dendritic arbor to produce a sequence of action potentials is among the
      most fundamental signal transformations that takes place within the central
      nervous system. Some aspects of this complex process, such as integration at the
      level of individual dendritic branches, have been extensively studied. But other
      aspects, such as how inputs from multiple branches are combined, and the kinetics
      of that integration have not been systematically examined. Using a 3D digital
      holographic photolysis technique to overcome the challenges posed by the
      complexities of the 3D anatomy of the dendritic arbor of CA1 pyramidal neurons
      for conventional photolysis, we show that integration on a single dendrite is
      fundamentally different from that on multiple dendrites. Multibranch integration
      occurring at oblique and basal dendrites allows somatic action potential firing
      of the cell to faithfully follow the driving stimuli over a significantly wider
      frequency range than what is possible with single branch integration. However,
      multibranch integration requires greater input strength to drive the somatic
      action potentials. This tradeoff between sensitivity and temporal precision may
      explain the puzzling report of the predominance of multibranch, rather than
      single branch, integration from in vivo recordings during presentation of visual
      stimuli. 

PMID- 24860428
TI  - Mitochondrial dysfunction induced by frataxin deficiency is associated with
      cellular senescence and abnormal calcium metabolism.
AB  - Friedreich ataxia is considered a neurodegenerative disorder involving both the
      peripheral and central nervous systems. Dorsal root ganglia (DRG) are the major
      target tissue structures. This neuropathy is caused by mutations in the FXN gene
      that encodes frataxin. Here, we investigated the mitochondrial and cell
      consequences of frataxin depletion in a cellular model based on frataxin
      silencing in SH-SY5Y human neuroblastoma cells, a cell line that has been used
      widely as in vitro models for studies on neurological diseases. We showed that
      the reduction of frataxin induced mitochondrial dysfunction due to a bioenergetic
      deficit and abnormal Ca(2+) homeostasis in the mitochondria that were associated
      with oxidative and endoplasmic reticulum stresses. The depletion of frataxin did
      not cause cell death but increased autophagy, which may have a cytoprotective
      effect against cellular insults such as oxidative stress. Frataxin silencing
      provoked slow cell growth associated with cellular senescence, as demonstrated by
      increased SA-betagal activity and cell cycle arrest at the G1 phase. We postulate
      that cellular senescence might be related to a hypoplastic defect in the DRG
      during neurodevelopment, as suggested by necropsy studies. 

PMID- 24860430
TI  - Plasticity of GABA transporters: an unconventional route to shape inhibitory
      synaptic transmission.
AB  - The brain relies on GABAergic neurons to control the ongoing activity of neuronal
      networks. GABAergic neurons control the firing pattern of excitatory cells, the
      temporal structure of membrane potential oscillations and the time window for
      integration of synaptic inputs. These actions require a fine control of the
      timing of GABA receptor activation which, in turn, depends on the precise timing
      of GABA release from pre-synaptic terminals and GABA clearance from the
      extracellular space. Extracellular GABA is not subject to enzymatic breakdown,
      and its clearance relies entirely on diffusion and uptake by specific
      transporters. In contrast to glutamate transporters, GABA transporters are
      abundantly expressed in neuronal pre-synaptic terminals. GABA transporters move
      laterally within the plasma membrane and are continuously trafficked to/from
      intracellular compartments. It is hypothesized that due to their proximity to
      GABA release sites, changes in the concentration and lateral mobility of GABA
      transporters may have a significant effect on the time course of the GABA
      concentration profile in and out of the synaptic cleft. To date, this hypothesis
      remains to be tested. Here we use 3D Monte Carlo reaction-diffusion simulations
      to analyze how changes in the density of expression and lateral mobility of GABA
      transporters in the cell membrane affect the extracellular GABA concentration
      profile and the activation of GABA receptors. Our results indicate that these
      manipulations mainly alter the GABA concentration profile away from the synaptic
      cleft. These findings provide novel insights into how the ability of GABA
      transporters to undergo plastic changes may alter the strength of GABAergic
      signals and the activity of neuronal networks in the brain. 

PMID- 24860431
TI  - Fractalkine regulation of microglial physiology and consequences on the brain and
      behavior.
AB  - Neural circuits are constantly monitored and supported by the surrounding
      microglial cells, using finely tuned mechanisms which include both direct contact
      and release of soluble factors. These bidirectional interactions are not only
      triggered by pathological conditions as a S.O.S. response to noxious stimuli, but
      they rather represent an established repertoire of dynamic communication for
      ensuring continuous immune surveillance and homeostasis in the healthy brain. In
      addition, recent studies are revealing key tasks for microglial interactions with
      neurons during normal physiological conditions, especially in regulating the
      maturation of neural circuits and shaping their connectivity in an activity- and
      experience-dependent manner. Chemokines, a family of soluble and membrane-bound
      cytokines, play an essential role in mediating neuron-microglia crosstalk in the
      developing and mature brain. As part of this special issue on Cytokines as
      players of neuronal plasticity and sensitivity to environment in healthy and
      pathological brain, our review focuses on the fractalkine signaling pathway,
      involving the ligand CX3CL1 which is mainly expressed by neurons, and its
      receptor CX3CR1 that is exclusively found on microglia within the healthy brain.
      An extensive literature largely based on transgenic mouse models has revealed
      that fractalkine signaling plays a critical role in regulating a broad spectrum
      of microglial properties during normal physiological conditions, especially their
      migration and dynamic surveillance of the brain parenchyma, in addition to
      influencing the survival of developing neurons, the maturation, activity and
      plasticity of developing and mature synapses, the brain functional connectivity,
      adult hippocampal neurogenesis, as well as learning and memory, and the
      behavioral outcome. 

PMID- 24860424
TI  - Protein phosphorylation in neurodegeneration: friend or foe?
AB  - Protein misfolding and aggregation is a common hallmark in neurodegenerative
      disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), and
      fronto-temporal dementia (FTD). In these disorders, the misfolding and
      aggregation of specific proteins occurs alongside neuronal degeneration in
      somewhat specific brain areas, depending on the disorder and the stage of the
      disease. However, we still do not fully understand the mechanisms governing
      protein aggregation, and whether this constitutes a protective or detrimental
      process. In PD, alpha-synuclein (aSyn) forms protein aggregates, known as Lewy
      bodies, and is phosphorylated at serine 129. Other residues have also been shown
      to be phosphorylated, but the significance of phosphorylation in the biology and
      pathophysiology of the protein is still controversial. In AD and in FTD,
      hyperphosphorylation of tau protein causes its misfolding and aggregation. Again,
      our understanding of the precise consequences of tau phosphorylation in the
      biology and pathophysiology of the protein is still limited. Through the use of a
      variety of model organisms and technical approaches, we are now gaining stronger
      insight into the effects of phosphorylation in the behavior of these proteins. In
      this review, we cover recent findings in the field and discuss how targeting
      phosphorylation events might be used for therapeutic intervention in these
      devastating diseases of the nervous system. 

PMID- 24860433
TI  - Fast detection of extrasynaptic GABA with a whole-cell sniffer.
AB  - Gamma-amino-butyric acid (GABA) is the main inhibitory transmitter of the brain.
      It operates by binding to specific receptors located both inside and outside
      synapses. The extrasynaptic receptors are activated by spillover from GABAergic
      synapses and by ambient GABA in the extracellular space. Ambient GABA is
      essential for adjusting the excitability of neurons. However, due to the lack of
      suitable methods, little is known about its dynamics. Here we describe a new
      technique that allows detection of GABA transients and measurement of the steady
      state GABA concentration with high spatial and temporal resolution. We used a
      human embryonic kidney (HEK) cell line that stably expresses GABAA receptors
      composed of alpha1, beta2, and gamma2 subunits. We recorded from such a HEK cell
      with the whole-cell patch-clamp technique. The presence of GABA near the HEK cell
      generated a measurable electric current whose magnitude increased with
      concentration. A fraction of the current did not inactivate during prolonged
      exposition to GABA. This technique, which we refer to as a "sniffer" allows the
      measurement of ambient GABA concentration inside nervous tissue with a resolution
      of few tens of nanomolars. In addition, the sniffer detects variations in the
      extrasynaptic GABA concentration with millisecond time resolution. Pilot
      experiments demonstrate that the sniffer is able to report spillover of GABA
      induced by synaptic activation in real time. This is the first report on a GABA
      sensor that combines the ability to detect fast transients and to measure steady
      concentrations. 

PMID- 24860432
TI  - The role of oxidative stress in degeneration of the neuromuscular junction in
      amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is characterized by the progressive loss of
      motoneurons and degradation of the neuromuscular junctions (NMJ). Consistent with
      the dying-back hypothesis of motoneuron degeneration the decline in synaptic
      function initiates from the presynaptic terminals in ALS. Oxidative stress is a
      major contributory factor to ALS pathology and affects the presynaptic
      transmitter releasing machinery. Indeed, in ALS mouse models nerve terminals are
      sensitive to reactive oxygen species (ROS) suggesting that oxidative stress,
      along with compromised mitochondria and increased intracellular Ca(2+) amplifies
      the presynaptic decline in NMJ. This initial dysfunction is followed by a
      neurodegeneration induced by inflammatory agents and loss of trophic support. To
      develop effective therapeutic approaches against ALS, it is important to identify
      the mechanisms underlying the initial pathological events. Given the role of
      oxidative stress in ALS, targeted antioxidant treatments could be a promising
      therapeutic approach. However, the complex nature of ALS and failure of
      monotherapies suggest that an antioxidant therapy should be accompanied by anti
      inflammatory interventions to enhance the restoration of the redox balance. 

PMID- 24860434
TI  - The relative contributions of MNTB and LNTB neurons to inhibition in the medial
      superior olive assessed through single and paired recordings.
AB  - The medial superior olive (MSO) senses microsecond differences in the coincidence
      of binaural signals, a critical cue for detecting sound location along the
      azimuth. An important component of this circuit is provided by inhibitory neurons
      of the medial and lateral nuclei of the trapezoid body (MNTB and LNTB,
      respectively). While MNTB neurons are fairly well described, little is known
      about the physiology of LNTB neurons. Using whole cell recordings from gerbil
      brainstem slices, we found that LNTB and MNTB neurons have similar membrane time
      constants and input resistances and fire brief action potentials, but only LNTB
      neurons fire repetitively in response to current steps. We observed that LNTB
      neurons receive graded excitatory and inhibitory synaptic inputs, with at least
      some of the latter arriving from other LNTB neurons. To address the relative
      timing of inhibition to the MSO from the LNTB versus the MNTB, we examined
      inhibitory responses to auditory nerve stimulation using a slice preparation that
      retains the circuitry from the auditory nerve to the MSO intact. Despite the
      longer physical path length of excitatory inputs driving contralateral
      inhibition, inhibition from both pathways arrived with similar latency and
      jitter. An analysis of paired whole cell recordings between MSO and MNTB neurons
      revealed a short and reliable delay between the action potential peak in MNTB
      neurons and the onset of the resulting IPSP (0.55 +/- 0.01 ms, n = 4, mean +/-
      SEM). Reconstructions of biocytin-labeled neurons showed that MNTB axons ranged
      from 580 to 858 MUm in length (n = 4). We conclude that while both LNTB and MNTB
      neurons provide similarly timed inhibition to MSO neurons, the reliability of
      inhibition from the LNTB at higher frequencies is more constrained relative to
      that from the MNTB due to differences in intrinsic properties, the strength of
      excitatory inputs, and the presence of feedforward inhibition. 

PMID- 24860435
TI  - Fernando de Castro and the discovery of the arterial chemoreceptors.
AB  - When de Castro entered the carotid body (CB) field, the organ was considered to
      be a small autonomic ganglion, a gland, a glomus or glomerulus, or a
      paraganglion. In his 1928 paper, de Castro concluded: "In sum, the Glomus
      caroticum is innervated by centripetal fibers, whose trophic centers are located
      in the sensory ganglia of the glossopharyngeal, and not by centrifugal [efferent]
      or secretomotor fibers as is the case for glands; these are precisely the facts
      which lead to suppose that the Glomus caroticum is a sensory organ." A few pages
      down, de Castro wrote: "The Glomus represents an organ with multiple receptors
      furnished with specialized receptor cells like those of other sensory organs
      [taste buds?]...As a plausible hypothesis we propose that the Glomus caroticum
      represents a sensory organ, at present the only one in its kind, dedicated to
      capture certain qualitative variations in the composition of blood, a function
      that, possibly by a reflex mechanism would have an effect on the functional
      activity of other organs... Therefore, the sensory fiber would not be directly
      stimulated by blood, but via the intermediation of the epithelial cells of the
      organ, which, as their structure suggests, possess a secretory function which
      would participate in the stimulation of the centripetal fibers." In our article
      we will recreate the experiments that allowed Fernando de Castro to reach this
      first conclusion. Also, we will scrutinize the natural endowments and the
      scientific knowledge that drove de Castro to make the triple hypotheses: the CB
      as chemoreceptor (variations in blood composition), as a secondary sensory
      receptor which functioning involves a chemical synapse, and as a center, origin
      of systemic reflexes. After a brief account of the systemic reflex effects
      resulting from the CB stimulation, we will complete our article with a general
      view of the cellular-molecular mechanisms currently thought to be involved in the
      functioning of this arterial chemoreceptor. 

PMID- 24860436
TI  - Localization of NG2 immunoreactive neuroglia cells in the rat locus coeruleus and
      their plasticity in response to stress.
AB  - The locus coeruleus (LC) nucleus modulates adaptive behavioral responses to
      stress and dysregulation of LC neuronal activity is implicated in stress-induced
      mental illnesses. The LC is composed primarily of noradrenergic neurons together
      with various glial populations. A neuroglia cell-type largely unexplored within
      the LC is the NG2 cell. NG2 cells serve primarily as oligodendrocyte precursor
      cells throughout the brain. However, some NG2 cells are in synaptic contact with
      neurons suggesting a role in information processing. The aim of this study was to
      neurochemically and anatomically characterize NG2 cells within the rat LC.
      Furthermore, since NG2 cells have been shown to proliferate in response to
      traumatic brain injury, we investigated whether such NG2 cells plasticity also
      occurs in response to emotive insults such as stress. Immunohistochemistry and
      confocal microscopy revealed that NG2 cells were enriched within the pontine
      region occupied by the LC. Close inspection revealed that a sub-population of NG2
      cells were located within unique indentations of LC noradrenergic somata and were
      immunoreactive for the neuronal marker NeuN whilst NG2 cell processes formed
      close appositions with clusters immunoreactive for the inhibitory synaptic marker
      proteins gephyrin and the GABA-A receptor alpha3-subunit, on noradrenergic
      dendrites. In addition, LC NG2 cell processes were decorated with vesicular
      glutamate transporter 2 immunoreactive puncta. Finally, 10 days of repeated
      restraint stress significantly increased the density of NG2 cells within the LC.
      The study demonstrates that NG2 IR cells are integral components of the LC
      cellular network and they exhibit plasticity as a result of emotive challenges. 

PMID- 24860437
TI  - Performance enhancement at the cost of potential brain plasticity: neural
      ramifications of nootropic drugs in the healthy developing brain.
AB  - Cognitive enhancement is perhaps one of the most intriguing and controversial
      topics in neuroscience today. Currently, the main classes of drugs used as
      potential cognitive enhancers include psychostimulants (methylphenidate (MPH),
      amphetamine), but wakefulness-promoting agents (modafinil) and glutamate
      activators (ampakine) are also frequently used. Pharmacologically, substances
      that enhance the components of the memory/learning circuits-dopamine, glutamate
      (neuronal excitation), and/or norepinephrine-stand to improve brain function in
      healthy individuals beyond their baseline functioning. In particular, non-medical
      use of prescription stimulants such as MPH and illicit use of psychostimulants
      for cognitive enhancement have seen a recent rise among teens and young adults in
      schools and college campuses. However, this enhancement likely comes with a
      neuronal, as well as ethical, cost. Altering glutamate function via the use of
      psychostimulants may impair behavioral flexibility, leading to the development
      and/or potentiation of addictive behaviors. Furthermore, dopamine and
      norepinephrine do not display linear effects; instead, their modulation of
      cognitive and neuronal function maps on an inverted-U curve. Healthy individuals
      run the risk of pushing themselves beyond optimal levels into hyperdopaminergic
      and hypernoradrenergic states, thus vitiating the very behaviors they are
      striving to improve. Finally, recent studies have begun to highlight potential
      damaging effects of stimulant exposure in healthy juveniles. This review explains
      how the main classes of cognitive enhancing drugs affect the learning and memory
      circuits, and highlights the potential risks and concerns in healthy individuals,
      particularly juveniles and adolescents. We emphasize the performance enhancement
      at the potential cost of brain plasticity that is associated with the neural
      ramifications of nootropic drugs in the healthy developing brain. 

PMID- 24860438
TI  - Attitudes toward pharmacological cognitive enhancement-a review.
AB  - A primary means for the augmentation of cognitive brain functions is
      "pharmacological cognitive enhancement" (PCE). The term usually refers to the off
      label use of medical substances to improve mental performance in healthy
      individuals. With the final aim to advance the normative debate taking place on
      that topic, several empirical studies have been conducted to assess the attitudes
      toward PCE in the public, i.e., in groups outside of the academic debate. In this
      review, we provide an overview of the 40 empirical studies published so far,
      reporting both their methodology and results. Overall, we find that several
      concerns about the use of PCE are prevalent in the public. These concerns largely
      match those discussed in the normative academic debate. We present our findings
      structured around the three most common concerns: medical safety, coercion, and
      fairness. Fairness is divided into three subthemes: equality of opportunity,
      honesty, and authenticity. Attitudes regarding some concerns are coherent across
      studies (e.g., coercion), whereas for others we find mixed results (e.g.,
      authenticity). Moreover, we find differences in how specific groups-such as
      users, nonusers, students, parents, and health care providers-perceive PCE: a
      coherent finding is that nonusers display more concerns regarding medical safety
      and fairness than users. We discuss potential psychological explanations for
      these differences. 

PMID- 24860439
TI  - The evolutionary neuroscience of musical beat perception: the Action Simulation
      for Auditory Prediction (ASAP) hypothesis.
AB  - EVERY HUMAN CULTURE HAS SOME FORM OF MUSIC WITH A BEAT: a perceived periodic
      pulse that structures the perception of musical rhythm and which serves as a
      framework for synchronized movement to music. What are the neural mechanisms of
      musical beat perception, and how did they evolve? One view, which dates back to
      Darwin and implicitly informs some current models of beat perception, is that the
      relevant neural mechanisms are relatively general and are widespread among animal
      species. On the basis of recent neural and cross-species data on musical beat
      processing, this paper argues for a different view. Here we argue that beat
      perception is a complex brain function involving temporally-precise communication
      between auditory regions and motor planning regions of the cortex (even in the
      absence of overt movement). More specifically, we propose that simulation of
      periodic movement in motor planning regions provides a neural signal that helps
      the auditory system predict the timing of upcoming beats. This "action simulation
      for auditory prediction" (ASAP) hypothesis leads to testable predictions. We
      further suggest that ASAP relies on dorsal auditory pathway connections between
      auditory regions and motor planning regions via the parietal cortex, and suggest
      that these connections may be stronger in humans than in non-human primates due
      to the evolution of vocal learning in our lineage. This suggestion motivates
      cross-species research to determine which species are capable of human-like beat
      perception, i.e., beat perception that involves accurate temporal prediction of
      beat times across a fairly broad range of tempi.

PMID- 24860440
TI  - CA1 hippocampal network activity changes during sleep-dependent memory
      consolidation.
AB  - A period of sleep over the first few hours following single-trial contextual fear
      conditioning (CFC) is essential for hippocampally-mediated memory consolidation.
      Recent studies have uncovered intracellular mechanisms required for memory
      formation which are affected by post-conditioning sleep and sleep deprivation.
      However, almost nothing is known about the circuit-level activity changes during
      sleep that underlie activation of these intracellular pathways. Here we
      continuously recorded from the CA1 region of freely-behaving mice to characterize
      neuronal and network activity changes occurring during active memory
      consolidation. C57BL/6J mice were implanted with custom stereotrode recording
      arrays to monitor activity of individual CA1 neurons, local field potentials
      (LFPs), and electromyographic activity. Sleep architecture and state-specific CA1
      activity patterns were assessed during a 24 h baseline recording period, and for
      24 h following either single-trial CFC or Sham conditioning. We find that
      consolidation of CFC is not associated with significant sleep architecture
      changes, but is accompanied by long-lasting increases in CA1 neuronal firing, as
      well as increases in delta, theta, and gamma-frequency CA1 LFP activity. These
      changes occurred in both sleep and wakefulness, and may drive synaptic plasticity
      within the hippocampus during memory formation. We also find that functional
      connectivity within the CA1 network, assessed through functional clustering
      algorithm (FCA) analysis of spike timing relationships among recorded neurons,
      becomes more stable during consolidation of CFC. This increase in network
      stability was not present following Sham conditioning, was most evident during
      post-CFC slow wave sleep (SWS), and was negligible during post-CFC wakefulness.
      Thus in the interval between encoding and recall, SWS may stabilize the
      hippocampal contextual fear memory (CFM) trace by promoting CA1 network
      stability. 

PMID- 24860441
TI  - Exploitation of puddles for breakthroughs in claustrum research.
AB  - Since its first identification as a thin strip of gray matter enclosed between
      stretches of neighboring fiber bundles, the claustrum has been considered
      impossible to study by many modern techniques that need a certain roominess of
      tissue for their application. Known as the front wall, vormauren in German from
      1822, and still called avant-mur in French, we here propose a means for breaking
      into and through this wall, by utilizing the instances where the claustral tissue
      itself has broken free into more spacious dimensions. This has occurred several
      times in the evolution of modern mammals, and all that needs be done is to
      exploit these natural expansions in order to take advantage of a great panoply of
      technological advances now at our disposal. So here we review the kinds of
      breakout "puddles" that await productive exploitation, to bring our knowledge of
      structure and function up to the level enjoyed for other more accessible regions
      of the brain. 

PMID- 24860442
TI  - Precentral gyrus functional connectivity signatures of autism.
AB  - Motor impairments are prevalent in children with autism spectrum disorders (ASD)
      and are perhaps the earliest symptoms to develop. In addition, motor skills
      relate to the communicative/social deficits at the core of ASD diagnosis, and
      these behavioral deficits may reflect abnormal connectivity within brain networks
      underlying motor control and learning. Despite the fact that motor abnormalities
      in ASD are well-characterized, there remains a fundamental disconnect between the
      complexity of the clinical presentation of ASD and the underlying neurobiological
      mechanisms. In this study, we examined connectivity within and between functional
      subregions of a key component of the motor control network, the precentral gyrus,
      using resting state functional Magnetic Resonance Imaging data collected from a
      large, heterogeneous sample of individuals with ASD as well as neurotypical
      controls. We found that the strength of connectivity within and between distinct
      functional subregions of the precentral gyrus was related to ASD diagnosis and to
      the severity of ASD traits. In particular, connectivity involving the dorsomedial
      (lower limb/trunk) subregion was abnormal in ASD individuals as predicted by
      models using a dichotomous variable coding for the presence of ASD, as well as
      models using symptom severity ratings. These findings provide further support for
      a link between motor and social/communicative abilities in ASD. 

PMID- 24860444
TI  - Decoding the ERD/ERS: influence of afferent input induced by a leg assistive
      robot.
AB  - This paper investigates the influence of the leg afferent input, induced by a leg
      assistive robot, on the decoding performance of a BMI system. Specifically, it
      focuses on a decoder based on the event-related (de)synchronization (ERD/ERS) of
      the sensorimotor area. The EEG experiment, performed with healthy subjects, is
      structured as a 3 * 2 factorial design, consisting of two factors: "finger
      tapping task" and "leg condition." The former is divided into three levels (BMI
      classes), being left hand finger tapping, right hand finger tapping and no
      movement (Idle); while the latter is composed by two levels: leg perturbed (Pert)
      and leg not perturbed (NoPert). Specifically, the subjects' leg was periodically
      perturbed by an assistive robot in 5 out of 10 sessions of the experiment and not
      moved in the remaining sessions. The aim of this study is to verify that the
      decoding performance of the finger tapping task is comparable between the two
      conditions NoPert and Pert. Accordingly, a classifier is trained to output the
      class of the finger tapping, given as input the features associated with the
      ERD/ERS. Individually for each subject, the decoding performance is statistically
      compared between the NoPert and Pert conditions. Results show that the decoding
      performance is notably above chance, for all the subjects, under both conditions.
      Moreover, the statistical comparison do not highlight a significant difference
      between NoPert and Pert in any subject, which is confirmed by feature
      visualization. 

PMID- 24860445
TI  - Minds, motherboards, and money: futurism and realism in the neuroethics of BCI
      technologies.

PMID- 24860443
TI  - The reactivation of somatosensory cortex and behavioral recovery after sensory
      loss in mature primates.
AB  - In our experiments, we removed a major source of activation of somatosensory
      cortex in mature monkeys by unilaterally sectioning the sensory afferents in the
      dorsal columns of the spinal cord at a high cervical level. At this level, the
      ascending branches of tactile afferents from the hand are cut, while other
      branches of these afferents remain intact to terminate on neurons in the dorsal
      horn of the spinal cord. Immediately after such a lesion, the monkeys seem
      relatively unimpaired in locomotion and often use the forelimb, but further
      inspection reveals that they prefer to use the unaffected hand in reaching for
      food. In addition, systematic testing indicates that they make more errors in
      retrieving pieces of food, and start using visual inspection of the rotated hand
      to confirm the success of the grasping of the food. Such difficulties are not
      surprising as a complete dorsal column lesion totally deactivates the
      contralateral hand representation in primary somatosensory cortex (area 3b).
      However, hand use rapidly improves over the first post-lesion weeks, and much of
      the hand representational territory in contralateral area 3b is reactivated by
      inputs from the hand in roughly a normal somatotopic pattern. Quantitative
      measures of single neuron response properties reveal that reactivated neurons
      respond to tactile stimulation on the hand with high firing rates and only
      slightly longer latencies. We conclude that preserved dorsal column afferents
      after nearly complete lesions contribute to the reactivation of cortex and the
      recovery of the behavior, but second-order sensory pathways in the spinal cord
      may also play an important role. Our microelectrode recordings indicate that
      these preserved first-order, and second-order pathways are initially weak and
      largely ineffective in activating cortex, but they are potentiated during the
      recovery process. Therapies that would promote this potentiation could usefully
      enhance recovery after spinal cord injury. 

PMID- 24860446
TI  - The vestibular system: a spatial reference for bodily self-consciousness.
AB  - Self-consciousness is the remarkable human experience of being a subject: the
      "I". Self-consciousness is typically bound to a body, and particularly to the
      spatial dimensions of the body, as well as to its location and displacement in
      the gravitational field. Because the vestibular system encodes head position and
      movement in three-dimensional space, vestibular cortical processing likely
      contributes to spatial aspects of bodily self-consciousness. We review here
      recent data showing vestibular effects on first-person perspective (the feeling
      from where "I" experience the world) and self-location (the feeling where "I" am
      located in space). We compare these findings to data showing vestibular effects
      on mental spatial transformation, self-motion perception, and body representation
      showing vestibular contributions to various spatial representations of the body
      with respect to the external world. Finally, we discuss the role for four
      posterior brain regions that process vestibular and other multisensory signals to
      encode spatial aspects of bodily self-consciousness: temporoparietal junction,
      parietoinsular vestibular cortex, ventral intraparietal region, and medial
      superior temporal region. We propose that vestibular processing in these cortical
      regions is critical in linking multisensory signals from the body (personal and
      peripersonal space) with external (extrapersonal) space. Therefore, the
      vestibular system plays a critical role for neural representations of spatial
      aspects of bodily self-consciousness. 

PMID- 24860448
TI  - Ways to investigate vestibular contributions to cognitive processes.

PMID- 24860450
TI  - EEG-microstate dependent emergence of perceptual awareness.
AB  - We investigated whether the differences in perceptual awareness for stimuli at
      the threshold of awareness can arise from different global brain states before
      stimulus onset indexed by the EEG microstate. We used a metacontrast backward
      masking paradigm in which subjects had to discriminate between two weak stimuli
      and obtained measures of accuracy and awareness while their EEG was recorded from
      256 channels. Comparing targets that were correctly identified with and without
      awareness allowed us to contrast differences in awareness while keeping
      performance constant for identical physical stimuli. Two distinct pre-stimulus
      scalp potential fields (microstate maps) dissociated correct identification with
      and without awareness, and their estimated intracranial generators were stronger
      in primary visual cortex before correct identification without awareness. This
      difference in activity cannot be explained by differences in alpha power or phase
      which were less reliably linked with differential pre-stimulus activation of
      primary visual cortex. Our results shed a new light on the function of pre
      stimulus activity in early visual cortex in visual awareness and emphasize the
      importance of trial-by-trials analysis of the spatial configuration of the scalp
      potential field identified with multichannel EEG. 

PMID- 24860449
TI  - Intrinsic properties and neuropharmacology of midline paraventricular thalamic
      nucleus neurons.
AB  - Neurons in the midline and intralaminar thalamic nuclei are components of an
      interconnected brainstem, limbic and prefrontal cortex neural network that is
      engaged during arousal, vigilance, motivated and addictive behaviors, and stress.
      To better understand the cellular mechanisms underlying these functions, here we
      review some of the recently characterized electrophysiological and
      neuropharmacological properties of neurons in the paraventricular thalamic
      nucleus (PVT), derived from whole cell patch clamp recordings in acute rat brain
      slice preparations. PVT neurons display firing patterns and ionic conductances
      (IT and IH) that exhibit significant diurnal change. Their resting membrane
      potential (RMP) is maintained by various ionic conductances that include inward
      rectifier (Kir), hyperpolarization-activated nonselective cation (HCN) and TWIK
      related acid sensitive (TASK) K(+) channels. Firing patterns are regulated by
      high voltage-activated (HVA) and low voltage-activated (LVA) Ca(2+) conductances.
      Moreover, transient receptor potential (TRP)-like nonselective cation channels
      together with Ca(2+)- and Na(+)-activated K(+) conductances (KCa; KNa) contribute
      to unique slow afterhyperpolarizing potentials (sAHPs) that are generally not
      detectable in lateral thalamic or reticular thalamic nucleus neurons. The
      excitability of PVT neurons is also modulated by activation of neurotransmitter
      receptors associated with afferent pathways to PVT and other thalamic midline
      nuclei. We report on receptor-mediated actions of GABA, glutamate, monoamines and
      several neuropeptides: arginine vasopressin, gastrin-releasing peptide,
      thyrotropin releasing hormone and the orexins (hypocretins). This review
      represents an initial survey of intrinsic and transmitter-sensitive ionic
      conductances that are deemed to be unique to this population of midline thalamic
      neurons, information that is fundamental to an appreciation of the role these
      thalamic neurons may play in normal central nervous system (CNS) physiology and
      in CNS disorders that involve the dorsomedial thalamus. 

PMID- 24860447
TI  - Recovery of neuronal and network excitability after spinal cord injury and
      implications for spasticity.
AB  - The state of areflexia and muscle weakness that immediately follows a spinal cord
      injury (SCI) is gradually replaced by the recovery of neuronal and network
      excitability, leading to both improvements in residual motor function and the
      development of spasticity. In this review we summarize recent animal and human
      studies that describe how motoneurons and their activation by sensory pathways
      become hyperexcitable to compensate for the reduction of functional activation of
      the spinal cord and the eventual impact on the muscle. Specifically, decreases in
      the inhibitory control of sensory transmission and increases in intrinsic
      motoneuron excitability are described. We present the idea that replacing lost
      patterned activation of the spinal cord by activating synaptic inputs via
      assisted movements, pharmacology or electrical stimulation may help to recover
      lost spinal inhibition. This may lead to a reduction of uncontrolled activation
      of the spinal cord and thus, improve its controlled activation by synaptic inputs
      to ultimately normalize circuit function. Increasing the excitation of the spinal
      cord with spared descending and/or peripheral inputs by facilitating movement,
      instead of suppressing it pharmacologically, may provide the best avenue to
      improve residual motor function and manage spasticity after SCI. 

PMID- 24860452
TI  - Changes of functional connectivity in the left frontoparietal network following
      aphasic stroke.
AB  - Language is an essential higher cognitive function supported by large-scale brain
      networks. In this study, we investigated functional connectivity changes in the
      left frontoparietal network (LFPN), a language-cognition related brain network in
      aphasic patients. We enrolled 13 aphasic patients who had undergone a stroke in
      the left hemisphere and age-, gender-, educational level-matched controls and
      analyzed the data by integrating independent component analysis (ICA) with a
      network connectivity analysis method. Resting state functional magnetic resonance
      imaging (fMRI) and clinical evaluation of language function were assessed at two
      stages: 1 and 2 months after stroke onset. We found reduced functional
      connectivity between the LFPN and the right middle frontal cortex, medial frontal
      cortex, and right inferior frontal cortex in aphasic patients as compared to
      controls. Correlation analysis showed that stronger functional connectivity
      between the LFPN and the right middle frontal cortex and medial frontal cortex
      coincided with more preserved language comprehension ability after stroke.
      Network connectivity analysis showed reduced LFPN connectivity as indicated by
      the mean network connectivity index of key regions in the LFPN of aphasic
      patients. The decreased LFPN connectivity in stroke patients was significantly
      associated with the impairment of language function in their comprehension
      ability. We also found significant association between recovery of comprehension
      ability and the mean changes in intrinsic LFPN connectivity. Our findings suggest
      that brain lesions may influence language comprehension by altering functional
      connectivity between regions and that the patterns of abnormal functional
      connectivity may contribute to the recovery of language deficits. 

PMID- 24860451
TI  - Stress induced a shift from dorsal hippocampus to prefrontal cortex dependent
      memory retrieval: role of regional corticosterone.
AB  - Most of the deleterious effects of stress on memory retrieval are due to a
      dysfunction of the hippocampo-prefrontal cortex interplay. The role of the stress
      induced regional corticosterone increase in such dysfunction remains however
      unclear, since there is no published study as yet dedicated to measuring
      corticosterone concentrations simultaneously in both the prefrontal cortex (mPFC)
      and the hippocampus (dHPC) in relation with memory impairments. To that aim, we
      first showed in Experiment 1 that an acute stress (3 electric footschocks; 0.9 mA
      each) delivered before memory testing reversed the memory retrieval pattern (MRP)
      in a serial discrimination task in which mice learned two successive
      discriminations. More precisely, whereas non-stressed animals remembered
      accurately the first learned discrimination and not the second one, stressed mice
      remembered more accurately the second discrimination but not the first one. We
      demonstrated that local inactivation of dHPC or mPFC with the anesthetic
      lidocaine recruited the dHPC activity in non-stress conditions whereas the stress
      induced MRP inversion recruited the mPFC activity. In a second experiment, we
      showed that acute stress induced a very similar time-course evolution of
      corticosterone rises within both the mPFC and dHPC. In a 3rd experiment, we found
      however that in situ injections of corticosterone either within the mPFC or the
      dHPC before memory testing favored the emergence of the mPFC-dependent MRP but
      blocked the emergence of the dHPC-dependent one. Overall, our study evidences
      that the simultaneous increase of corticosterone after stress in both areas
      induces a shift from dHPC (non-stress condition) to mPFC-dependent MRP and that
      corticosterone is critically involved in mediating the deleterious effects of
      stress on cognitive functions involving the mPFC-HPC interplay. 

PMID- 24860453
TI  - Lateral Habenula determines long-term storage of aversive memories.
AB  - The Lateral Habenula (LHb) is a small brain structure that codifies negative
      motivational value and has been related to major depression. It has been shown
      recently that LHb activation is sufficient to induce aversive associative
      learning; however the key question about whether LHb activation is required for
      an aversive memory to be formed has not been addressed. In this article we
      studied the function of the LHb in memory formation using the Inhibitory
      Avoidance task (IA). We found that LHb inactivation during IA training does not
      disrupt memory when assessed 24 h after, but abolishes it 7 days later,
      indicating that LHb activity during memory acquisition is not necessary for
      memory formation, but regulates its temporal stability. These effects suggest
      that LHb inactivation modifies subjective perception of the training experience. 

PMID- 24860454
TI  - Mismatch negativity and p3a/reorienting complex in subjects with schizophrenia or
      at-risk mental state.
AB  - INTRODUCTION: We measured duration mismatch negativity (dMMN), P3a, and
      reorienting negativity (RON) in subjects with at-risk mental state (ARMS),
      patients with first-episode or chronic schizophrenia, and healthy volunteers. The
      main interest was to determine if these event-related potentials provide a
      biomarker associated with progression to overt schizophrenia in ARMS subjects.
      METHODS: Nineteen ARMS subjects meeting the criteria of the Comprehensive
      Assessment of ARMS, 38 patients with schizophrenia (19 first-episode and 19
      chronic), and 19 healthy controls participated in the study. dMMN, P3a, and RON
      were measured with an auditory odd-ball paradigm at baseline. RESULTS: During the
      follow-up period (2.2 years), 4 out of the 19 ARMS subjects transitioned to
      schizophrenia (Converters) while 15 did not (non-Converters). dMMN amplitudes of
      Converters were significantly smaller than those of non-Converters at frontal and
      central electrodes before onset of illness. dMMN amplitudes of non-Converters did
      not differ from those of healthy controls, while Converters showed significantly
      smaller dMMN amplitudes compared to control subjects. RON amplitudes were also
      reduced at frontal and central electrodes in subjects with schizophrenia, but not
      ARMS. Converter subjects tended to show smaller RON amplitudes compared to non
      Converters. CONCLUSIONS: Our data confirm that diminished dMMN amplitudes provide
      a biomarker, which is present before and after the development of psychosis. In
      this respect, RON amplitudes may also be useful, as suggested for the first time
      based on longitudinal observations.

PMID- 24860455
TI  - Induction of aversive learning through thermogenetic activation of Kenyon cell
      ensembles in Drosophila.
AB  - Drosophila represents a model organism to analyze neuronal mechanisms underlying
      learning and memory. Kenyon cells of the Drosophila mushroom body are required
      for associative odor learning and memory retrieval. But is the mushroom body
      sufficient to acquire and retrieve an associative memory? To answer this question
      we have conceived an experimental approach to bypass olfactory sensory input and
      to thermogenetically activate sparse and random ensembles of Kenyon cells
      directly. We found that if the artifical activation of Kenyon cell ensembles
      coincides with a salient, aversive stimulus learning was induced. The animals
      adjusted their behavior in a subsequent test situation and actively avoided
      reactivation of these Kenyon cells. Our results show that Kenyon cell activity in
      coincidence with a salient aversive stimulus can suffice to form an associative
      memory. Memory retrieval is characterized by a closed feedback loop between a
      behavioral action and the reactivation of sparse ensembles of Kenyon cells. 

PMID- 24860456
TI  - Loss of Nogo receptor homolog NgR2 alters spine morphology of CA1 neurons and
      emotionality in adult mice.
AB  - Molecular mechanisms which stabilize dendrites and dendritic spines are essential
      for regulation of neuronal plasticity in development and adulthood. The class of
      Nogo receptor proteins, which are critical for restricting neurite outgrowth
      inhibition signaling, have been shown to have roles in developmental, experience
      and activity induced plasticity. Here we investigated the role of the Nogo
      receptor homolog NgR2 in structural plasticity in a transgenic null mutant for
      NgR2. Using Golgi-Cox staining to analyze morphology, we show that loss of NgR2
      alters spine morphology in adult CA1 pyramidal neurons of the hippocampus,
      significantly increasing mushroom-type spines, without altering dendritic tree
      complexity. Furthermore, this shift is specific to apical dendrites in distal CA1
      stratum radiatum (SR). Behavioral alterations in NgR2(-/-) mice were investigated
      using a battery of standardized tests and showed that whilst there were no
      alterations in learning and memory in NgR2(-/-) mice compared to littermate
      controls, NgR2(-/-) displayed reduced fear expression in the contextual
      conditioned fear test, and exhibited reduced anxiety- and depression-related
      behaviors. This suggests that the loss of NgR2 results in a specific phenotype of
      reduced emotionality. We conclude that NgR2 has role in maintenance of mature
      spines and may also regulate fear and anxiety-like behaviors. 

PMID- 24860457
TI  - Infant rats can learn time intervals before the maturation of the striatum:
      evidence from odor fear conditioning.
AB  - Interval timing refers to the ability to perceive, estimate and discriminate
      durations in the range of seconds to minutes. Very little is currently known
      about the ontogeny of interval timing throughout development. On the other hand,
      even though the neural circuit sustaining interval timing is a matter of debate,
      the striatum has been suggested to be an important component of the system and
      its maturation occurs around the third post-natal (PN) week in rats. The global
      aim of the present study was to investigate interval timing abilities at an age
      for which striatum is not yet mature. We used odor fear conditioning, as it can
      be applied to very young animals. In odor fear conditioning, an odor is presented
      to the animal and a mild footshock is delivered after a fixed interval. Adult
      rats have been shown to learn the temporal relationships between the odor and the
      shock after a few associations. The first aim of the present study was to assess
      the activity of the striatum during odor fear conditioning using 2-Deoxyglucose
      autoradiography during development in rats. The data showed that although fear
      learning was displayed at all tested ages, activation of the striatum was
      observed in adults but not in juvenile animals. Next, we assessed the presence of
      evidence of interval timing in ages before and after the inclusion of the
      striatum into the fear conditioning circuit. We used an experimental setup
      allowing the simultaneous recording of freezing and respiration that have been
      demonstrated to be sensitive to interval timing in adult rats. This enabled the
      detection of duration-related temporal patterns for freezing and/or respiration
      curves in infants as young as 12 days PN during odor fear conditioning. This
      suggests that infants are able to encode time durations as well as and as quickly
      as adults while their striatum is not yet functional. Alternative networks
      possibly sustaining interval timing in infant rats are discussed. 

PMID- 24860458
TI  - Dynamic network participation of functional connectivity hubs assessed by resting
      state fMRI.
AB  - Network studies of large-scale brain connectivity have demonstrated that highly
      connected areas, or "hubs," are a key feature of human functional and structural
      brain organization. We use resting-state functional MRI data and connectivity
      clustering to identify multi-network hubs and show that while hubs can belong to
      multiple networks their degree of integration into these different networks
      varies dynamically over time. The extent of the network variation was related to
      the connectedness of the hub. In addition, we found that these network dynamics
      were inversely related to positive self-generated thoughts reported by
      individuals and were further decreased with older age. Moreover, the left caudate
      varied its degree of participation between a default mode subnetwork and a limbic
      network. This variation was predictive of individual differences in the reports
      of past-related thoughts. These results support an association between ongoing
      thought processes and network dynamics and offer a new approach to investigate
      the brain dynamics underlying mental experience. 

PMID- 24860459
TI  - Effects of robot assisted gait training in progressive supranuclear palsy (PSP):
      a preliminary report.
AB  - BACKGROUND AND PURPOSE: Progressive supranuclear palsy (PSP) is a rare
      neurodegenerative disease clinically characterized by prominent axial
      extrapyramidal motor symptoms with frequent falls. Over the last years the
      introduction of robotic technologies to recover lower limb function has been
      greatly employed in the rehabilitative practice. This observational trial is
      aimed at investigating the changes in the main spatiotemporal following end
      effector robot training in people with PSP. METHOD: Pilot observational trial.
      PARTICIPANTS: Five cognitively intact participants with PSP and gait disorders.
      INTERVENTIONS: Patients were submitted to a rehabilitative program of robot
      assisted walking sessions for 45 min, 5 times a week for 4 weeks. MAIN OUTCOME
      MEASURES: The spatiotemporal parameters at the beginning (T0) and at the end of
      treatment (T1) were recorded by a gait analysis laboratory. RESULTS: Robot
      training was feasible, acceptable and safe and all participants completed the
      prescribed training sessions. All patients showed an improvement in the gait
      spatiotemporal index (Mean velocity, Cadence, Step length, and Step width) (T0
      vs. T1). CONCLUSIONS: Robot training is a feasible and safe form of
      rehabilitation for cognitively intact people with PSP. The lack of side effects
      and the positive results in the gait parameter index in all patients support the
      recommendation to extend the trials of this treatment. Further investigation
      regarding the effectiveness of robot training in time is necessary. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT01668407.

PMID- 24860460
TI  - Lexical-perceptual integration influences sensorimotor adaptation in speech.
AB  - A combination of lexical bias and altered auditory feedback was used to
      investigate the influence of higher-order linguistic knowledge on the perceptual
      aspects of speech motor control. Subjects produced monosyllabic real words or
      pseudo-words containing the vowel [epsilon] (as in "head") under conditions of
      altered auditory feedback involving a decrease in vowel first formant (F1)
      frequency. This manipulation had the effect of making the vowel sound more
      similar to [I] (as in "hid"), affecting the lexical status of produced words in
      two Lexical-Change (LC) groups (either changing them from real words to pseudo
      words: e.g., less-liss, or pseudo-words to real words: e.g., kess-kiss). Two Non
      Lexical-Change (NLC) control groups underwent the same auditory feedback
      manipulation during the production of [epsilon] real- or pseudo-words, only
      without any resulting change in lexical status (real words to real words: e.g.,
      mess-miss, or pseudo-words to pseudo-words: e.g., ness-niss). The results from
      the LC groups indicate that auditory-feedback-based speech motor learning is
      sensitive to the lexical status of the stimuli being produced, in that speakers
      tend to keep their acoustic speech outcomes within the auditory-perceptual space
      corresponding to the task-related side of the word/non-word boundary (real words
      or pseudo-words). For the NLC groups, however, no such effect of lexical status
      is observed. 

PMID- 24860461
TI  - Neural repetition suppression: evidence for perceptual expectation in object
      selective regions.
AB  - It is an established finding that neuronal activity is decreased for repeated
      stimuli. Recent studies revealed that repetition suppression (RS) effects are
      altered by manipulating the probability with which stimuli are repeated. RS for
      faces is more pronounced when the probability of repetition is high than when it
      is low. This response pattern is interpreted with reference to the predictive
      coding (PC) account, which assumes that RS is influenced by top-down
      expectations. Recent findings challenge the generality of PC accounts of RS by
      showing repetition probability does not modulate RS for other visual stimuli than
      faces. However, a number of findings on visual processing are in line with PC.
      Thus, the influence of repetition probability on RS effects during object
      processing requires careful reinvestigations. In the present fMRI study, object
      pictures were presented in a high (75%) or low (25%) repetition probability
      context. We found increased RS in the high-probability context compared to the
      low-probability context in the left lateral occipital complex (LOC). The dorsal
      caudal and the ventral-anterior subdivisions of the LOC revealed similar neuronal
      responses. These results indicate that repetition probability effects can be
      found for other visual objects than faces and provide evidence in favor of the PC
      account. 

PMID- 24860463
TI  - Open questions on the mechanisms of neuromodulation with applied and endogenous
      electric fields.

PMID- 24860462
TI  - The compensatory dynamic of inter-hemispheric interactions in visuospatial
      attention revealed using rTMS and fMRI.
AB  - A balance of mutual tonic inhibition between bi-hemispheric posterior parietal
      cortices is believed to play an important role in bilateral visual attention.
      However, experimental support for this notion has been mainly drawn from clinical
      models of unilateral damage. We have previously shown that low-frequency
      repetitive TMS (rTMS) over the intraparietal sulcus (IPS) generates a
      contralateral attentional deficit in bilateral visual tracking. Here, we used
      functional magnetic resonance imaging (fMRI) to study whether rTMS temporarily
      disrupts the inter-hemispheric balance between bilateral IPS in visual attention.
      Following application of 1 Hz rTMS over the left IPS, subjects performed a
      bilateral visual tracking task while their brain activity was recorded using
      fMRI. Behaviorally, tracking accuracy was reduced immediately following rTMS.
      Areas ventro-lateral to left IPS, including inferior parietal lobule (IPL),
      lateral IPS (LIPS), and middle occipital gyrus (MoG), showed decreased activity
      following rTMS, while dorsomedial areas, such as Superior Parietal Lobule (SPL),
      Superior occipital gyrus (SoG), and lingual gyrus, as well as middle temporal
      areas (MT+), showed higher activity. The brain activity of the homologues of
      these regions in the un-stimulated, right hemisphere was reversed. Interestingly,
      the evolution of network-wide activation related to attentional behavior
      following rTMS showed that activation of most occipital synergists adaptively
      compensated for contralateral and ipsilateral decrement after rTMS, while
      activation of parietal synergists, and SoG remained competing. This pattern of
      ipsilateral and contralateral activations empirically supports the hypothesized
      loss of inter-hemispheric balance that underlies clinical manifestation of visual
      attentional extinction. 

PMID- 24860465
TI  - The searching for autism biomarkers: a commentary on: a new methodology of
      viewing extra-axial fluid and cortical abnormalities in children with autism via
      transcranial ultrasonography.

PMID- 24860464
TI  - "The wondrous eyes of a new technology"-a history of the early
      electroencephalography (EEG) of psychopathy, delinquency, and immorality.
AB  - This article presents a history of the early electroencephalography (EEG) of
      psychopathy, delinquency, and immorality in Great Britain and the United States
      in the 1940s and 1950s. Then, EEG was a novel research tool that promised ground
      breaking insights in psychiatry and criminology. Experts explored its potential
      regarding the diagnosis, classification, etiology, and treatment of unethical and
      unlawful persons. This line of research yielded tentative and inconsistent
      findings, which the experts attributed to methodological and theoretical
      shortcomings. Accordingly, the scientific community discussed the reliability,
      validity, and utility of EEG, and launched initiatives to calibrate and
      standardize the novel tool. The analysis shows that knowledge production, gauging
      of the research tool, and attempts to establish credibility for EEG in the study
      of immoral persons occurred simultaneously. The paper concludes with a reflection
      on the similarities between EEG and neuroimaging-the prime research tool in the
      current neuroscience of morality-and calls for a critical assessment of their
      potentials and limitations in the study of immorality and crime. 

PMID- 24860467
TI  - Sustained posterior contralateral activity indicates re-entrant target processing
      in visual change detection: an EEG study.
AB  - The present study investigated the neural mechanisms that contribute to the
      detection of visual feature changes between stimulus displays by means of event
      related lateralizations of the electroencephalogram (EEG). Participants were
      instructed to respond to a luminance change in either of two lateralized stimuli
      that could randomly occur alone or together with an irrelevant orientation change
      of the same or contralateral stimulus. Task performance based on response times
      and accuracy was decreased compared to the remaining stimulus conditions when
      relevant and irrelevant feature changes were presented contralateral to each
      other (contralateral distractor condition). The sensory response to the feature
      changes was reflected in a posterior contralateral positivity at around 100 ms
      after change presentation and a posterior contralateral negativity in the N1 time
      window (N1pc). N2pc reflected a subsequent attentional bias in favor of the
      relevant luminance change. The continuation of the sustained posterior
      contralateral negativity (SPCN) following N2pc covaried with response times
      within feature change conditions and revealed a posterior topography comparable
      to the earlier components associated with sensory and attentional mechanisms.
      Therefore, this component might reflect the re-processing of information based on
      sustained short-term memory representations in the visual system until a stable
      target percept is created that can serve as the perceptual basis for response
      selection and the initiation of goal-directed behavior. 

PMID- 24860466
TI  - Structural changes induced by daily music listening in the recovering brain after
      middle cerebral artery stroke: a voxel-based morphometry study.
AB  - Music is a highly complex and versatile stimulus for the brain that engages many
      temporal, frontal, parietal, cerebellar, and subcortical areas involved in
      auditory, cognitive, emotional, and motor processing. Regular musical activities
      have been shown to effectively enhance the structure and function of many brain
      areas, making music a potential tool also in neurological rehabilitation. In our
      previous randomized controlled study, we found that listening to music on a daily
      basis can improve cognitive recovery and improve mood after an acute middle
      cerebral artery stroke. Extending this study, a voxel-based morphometry (VBM)
      analysis utilizing cost function masking was performed on the acute and 6-month
      post-stroke stage structural magnetic resonance imaging data of the patients (n =
      49) who either listened to their favorite music [music group (MG), n = 16] or
      verbal material [audio book group (ABG), n = 18] or did not receive any listening
      material [control group (CG), n = 15] during the 6-month recovery period.
      Although all groups showed significant gray matter volume (GMV) increases from
      the acute to the 6-month stage, there was a specific network of frontal areas
      [left and right superior frontal gyrus (SFG), right medial SFG] and limbic areas
      [left ventral/subgenual anterior cingulate cortex (SACC) and right ventral
      striatum (VS)] in patients with left hemisphere damage in which the GMV increases
      were larger in the MG than in the ABG and in the CG. Moreover, the GM
      reorganization in the frontal areas correlated with enhanced recovery of verbal
      memory, focused attention, and language skills, whereas the GM reorganization in
      the SACC correlated with reduced negative mood. This study adds on previous
      results, showing that music listening after stroke not only enhances behavioral
      recovery, but also induces fine-grained neuroanatomical changes in the recovering
      brain. 

PMID- 24860468
TI  - The affordance-matching hypothesis: how objects guide action understanding and
      prediction.
AB  - Action understanding lies at the heart of social interaction. Prior research has
      often conceptualized this capacity in terms of a motoric matching of observed
      actions to an action in one's motor repertoire, but has ignored the role of
      object information. In this manuscript, we set out an alternative conception of
      intention understanding, which places the role of objects as central to our
      observation and comprehension of the actions of others. We outline the current
      understanding of the interconnectedness of action and object knowledge,
      demonstrating how both rely heavily on the other. We then propose a novel
      framework, the affordance-matching hypothesis, which incorporates these findings
      into a simple model of action understanding, in which object knowledge-what an
      object is for and how it is used-can inform and constrain both action
      interpretation and prediction. We will review recent empirical evidence that
      supports such an object-based view of action understanding and we relate the
      affordance matching hypothesis to recent proposals that have re-conceptualized
      the role of mirror neurons in action understanding. 

PMID- 24860469
TI  - Monetary rewards modulate inhibitory control.
AB  - The ability to override a dominant response, often referred to as behavioral
      inhibition, is considered a key element of executive cognition. Poor behavioral
      inhibition is a defining characteristic of several neurological and psychiatric
      populations. Recently, there has been increasing interest in the motivational
      dimension of behavioral inhibition, with some experiments incorporating emotional
      contingencies in classical inhibitory paradigms such as the Go/NoGo and Stop
      Signal Tasks (SSTs). Several studies have reported a positive modulatory effect
      of reward on performance in pathological conditions such as substance abuse,
      pathological gambling, and Attention Deficit Hyperactive Disorder (ADHD).
      However, experiments that directly investigate the modulatory effects of reward
      magnitudes on the performance of inhibitory tasks are scarce and little is known
      about the finer grained relationship between motivation and inhibitory control.
      Here we probed the effect of reward magnitude and context on behavioral
      inhibition with three modified versions of the widely used SST. The pilot study
      compared inhibition performance during six blocks alternating neutral feedback,
      low, medium, and high monetary rewards. Study One compared increasing vs.
      decreasing rewards, with low, high rewards, and neutral feedback; whilst Study
      Two compared low and high reward magnitudes alone also in an increasing and
      decreasing reward design. The reward magnitude effect was not demonstrated in the
      pilot study, probably due to a learning effect induced by practice in this
      lengthy task. The reward effect per se was weak but the context (order of reward)
      was clearly suggested in Study One, and was particularly strongly confirmed in
      study two. In addition, these findings revealed a "kick start effect" over global
      performance measures. Specifically, there was a long lasting improvement in
      performance throughout the task when participants received the highest reward
      magnitudes at the beginning of the protocol. These results demonstrate a
      dynamical behavioral inhibition capacity in humans, as illustrated by the reward
      magnitude modulation and initial reward history effects. 

PMID- 24860470
TI  - Assimilation of L2 vowels to L1 phonemes governs L2 learning in adulthood: a
      behavioral and ERP study.
AB  - According to the Perceptual Assimilation Model (PAM), articulatory
      similarity/dissimilarity between sounds of the second language (L2) and the
      native language (L1) governs L2 learnability in adulthood and predicts L2 sound
      perception by naive listeners. We performed behavioral and neurophysiological
      experiments on two groups of university students at the first and fifth years of
      the English language curriculum and on a group of naive listeners. Categorization
      and discrimination tests, as well as the mismatch negativity (MMN) brain response
      to L2 sound changes, showed that the discriminatory capabilities of the students
      did not significantly differ from those of the naive subjects. In line with the
      PAM model, we extend the findings of previous behavioral studies showing that, at
      the neural level, classroom instruction in adulthood relies on assimilation of L2
      vowels to L1 phoneme categories and does not trigger improvement in L2 phonetic
      discrimination. Implications for L2 classroom teaching practices are discussed. 

PMID- 24860471
TI  - Overestimation of the second time interval replaces time-shrinking when the
      difference between two adjacent time intervals increases.
AB  - When the onsets of three successive sound bursts mark two adjacent time
      intervals, the second time interval can be underestimated when it is physically
      longer than the first time interval by up to 100 ms. This illusion, time
      shrinking, is very stable when the first time interval is 200 ms or shorter
      (Nakajima et al., 2004, Perception, 33). Time-shrinking had been considered a
      kind of perceptual assimilation to make the first and the second time interval
      more similar to each other. Here we investigated whether the underestimation of
      the second time interval was replaced by an overestimation if the physical
      difference between the neighboring time intervals was too large for the
      assimilation to take place; this was a typical situation in which a perceptual
      contrast could be expected. Three experiments to measure the
      overestimation/underestimation of the second time interval by the method of
      adjustment were conducted. The first time interval was varied from 40 to 280 ms,
      and such overestimations indeed took place when the first time interval was 80
      280 ms. The overestimations were robust when the second time interval was longer
      than the first time interval by 240 ms or more, and the magnitude of the
      overestimation was larger than 100 ms in some conditions. Thus, a perceptual
      contrast to replace time-shrinking was established. An additional experiment
      indicated that this contrast did not affect the perception of the first time
      interval substantially: The contrast in the present conditions seemed unilateral.

PMID- 24860472
TI  - Ancient evolutionary origins of epigenetic regulation associated with
      posttraumatic stress disorder.
AB  - Epigenetic marks, including DNA methylation, are modifiable molecular factors
      that may underlie mental disorders, especially responses to trauma, including the
      development of and resilience to posttraumatic stress disorder (PTSD). Previous
      work has identified differential DNA methylation at CpG dinucleotide sites
      genomewide between trauma exposed individuals with and without PTSD, suggesting a
      role for epigenetic potential-the capacity to epigenetically regulate behavior
      and physiology in response to lived experiences. The human species is
      characterized by an increased period of adaptive plasticity during brain
      development. The evolutionary history of epigenetic potential in relation to
      adaptive plasticity is currently unknown. Using phylogenetic methods and
      functional annotation analyses, we trace the evolution of over 7000 CpG
      dinucleotides, including 203 associated with PTSD, during the descent of humans
      in during mammalian evolution and characterize the biological significance of
      this evolution. We demonstrate that few (7%) PTSD-associated CpG sites are unique
      to humans, while the vast majority of sites have deep evolutionary origins: 73
      and 93% were unambiguously present in the last common ancestor of
      humans/orangutans and humans/chimpanzees, respectively. Genes proximal to evolved
      PTSD-associated CpG sites revealed significant enrichment for immune function
      during recent human evolution and regulation of gene expression during more
      ancient periods of human evolution. Additionally, 765 putative transcription
      factor binding motifs (TFBMs) were identified that overlap with PTSD-associated
      CpG sites. Elucidation of the evolutionary history of PTSD-associated CpG sites
      may provide insights into the function and origin of epigenetic potential in
      trauma responses, generally, and PTSD, specifically. The human capacity to
      respond to trauma with stable physiologic and behavioral changes may be due to
      epigenetic potentials that are shared among many mammalian species. 

PMID- 24860473
TI  - Successful tactile based visual sensory substitution use functions independently
      of visual pathway integrity.
AB  - PURPOSE: Neuronal reorganization after blindness is of critical interest because
      it has implications for the rational prescription of artificial vision devices.
      The purpose of this study was to distinguish the microstructural differences
      between perinatally blind (PB), acquired blind (AB), and normally sighted
      controls (SCs) and relate these differences to performance on functional tasks
      using a sensory substitution device (BrainPort). METHODS: We enrolled 52 subjects
      (PB n = 11; AB n = 35; SC n = 6). All subjects spent 15 h undergoing BrainPort
      device training. Outcomes of light perception, motion, direction, temporal
      resolution, grating, and acuity were tested at baseline and after training.
      Twenty-six of the subjects were scanned with a three Tesla MRI scanner for
      diffusion tensor imaging (DTI), and with a positron emission tomography (PET)
      scanner for mapping regional brain glucose consumption during sensory
      substitution function. Non-parametric models were used to analyze fractional
      anisotropy (FA; a DTI measure of microstructural integrity) of the brain via
      region-of-interest (ROI) analysis and tract-based spatial statistics (TBSS).
      RESULTS: At baseline, all subjects performed all tasks at chance level. After
      training, light perception, time resolution, location and grating acuity tasks
      improved significantly for all subject groups. ROI and TBSS analyses of FA maps
      show areas of statistically significant differences (p <= 0.025) in the bilateral
      optic radiations and some visual association connections between all three
      groups. No relationship was found between FA and functional performance with the
      BrainPort. DISCUSSION: All subjects showed performance improvements using the
      BrainPort irrespective of nature and duration of blindness. Definite brain areas
      with significant microstructural integrity changes exist among PB, AB, and NC,
      and these variations are most pronounced in the visual pathways. However, the use
      of sensory substitution devices is feasible irrespective of microstructural
      integrity of the primary visual pathways between the eye and the brain.
      Therefore, tongue based devices devices may be usable for a broad array of non
      sighted patients.

PMID- 24860474
TI  - Cerebral functional imaging using near-infrared spectroscopy during repeated
      performances of motor rehabilitation tasks tested on healthy subjects.
AB  - To investigate the relationship between the frontal and sensorimotor cortices and
      motor learning, hemodynamic responses were recorded from the frontal and
      sensorimotor cortices using functional near infrared spectroscopy (NIRS) while
      healthy subjects performed motor learning tasks used in rehabilitation medicine.
      Whole-head NIRS recordings indicated that response latencies in the anterior
      dorsomedial prefrontal cortex (aDMPFC) were shorter than in other frontal and
      parietal areas. Furthermore, the increment rate of the hemodynamic responses in
      the aDMPFC across the eight repeated trials significantly correlated with those
      in the other areas, as well as with the improvement rate of task performance
      across the 8 repeated trials. In the second experiment, to dissociate scalp- and
      brain-derived hemodynamic responses, hemodynamic responses were recorded from the
      head over the aDMPFC using a multi-distance probe arrangement. Six probes (a
      single source probe and 5 detectors) were linearly placed 6 mm apart from each of
      the neighboring probes. Using independent component analyses of hemodynamic
      signals from the 5 source-detector pairs, we dissociated scalp- and brain-derived
      components of the hemodynamic responses. Hemodynamic responses corrected for
      scalp-derived responses over the aDMPFC significantly increased across the 8
      trials and correlated with task performance. In the third experiment, subjects
      were required to perform the same task with and without transcranial direct
      current stimulation (tDCS) of the aDMPFC before the task. The tDCS significantly
      improved task performance. These results indicate that the aDMPFC is crucial for
      improved performance in repetitive motor learning. 

PMID- 24860475
TI  - Navigating actions through the rodent parietal cortex.
AB  - The posterior parietal cortex (PPC) participates in a manifold of cognitive
      functions, including visual attention, working memory, spatial processing, and
      movement planning. Given the vast interconnectivity of PPC with sensory and motor
      areas, it is not surprising that neuronal recordings show that PPC often encodes
      mixtures of spatial information as well as the movements required to reach a
      goal. Recent work sought to discern the relative strength of spatial vs. motor
      signaling in PPC by recording single unit activity in PPC of freely behaving rats
      during selective changes in either the spatial layout of the local environment or
      in the pattern of locomotor behaviors executed during navigational tasks. The
      results revealed unequivocally a predominant sensitivity of PPC neurons to
      locomotor action structure, with subsets of cells even encoding upcoming
      movements more than 1 s in advance. In light of these and other recent findings
      in the field, I propose that one of the key contributions of PPC to navigation is
      the synthesis of goal-directed behavioral sequences, and that the rodent PPC may
      serve as an apt system to investigate cellular mechanisms for spatial motor
      planning as traditionally studied in humans and monkeys. 

PMID- 24860476
TI  - Music as a mnemonic to learn gesture sequences in normal aging and Alzheimer's
      disease.
AB  - Strong links between music and motor functions suggest that music could represent
      an interesting aid for motor learning. The present study aims for the first time
      to test the potential of music to assist in the learning of sequences of gestures
      in normal and pathological aging. Participants with mild Alzheimer's disease (AD)
      and healthy older adults (controls) learned sequences of meaningless gestures
      that were either accompanied by music or a metronome. We also manipulated the
      learning procedure such that participants had to imitate the gestures to-be
      memorized in synchrony with the experimenter or after the experimenter during
      encoding. Results show different patterns of performance for the two groups.
      Overall, musical accompaniment had no impact on the controls' performance but
      improved those of AD participants. Conversely, synchronization of gestures during
      learning helped controls but seemed to interfere with retention in AD. We discuss
      these findings regarding their relevance for a better understanding of auditory
      motor memory, and we propose recommendations to maximize the mnemonic effect of
      music for motor sequence learning for dementia care. 

PMID- 24860477
TI  - The face inversion effect in opponent-stimulus rivalry.
AB  - The face inversion effect is regarded as a hallmark of face-specific processing,
      and can be observed in a large variety of visual tasks. Face inversion effects
      are also reported in binocular rivalry. However, it is unclear whether these
      effects are face-specific, and distinct from the general tendency of visual
      awareness to privilege upright objects. We studied continuous rivalry across more
      than 600 dominance epochs for each observer, having faces and houses rival
      against their inverted counterparts, and letting faces rival against houses in
      both upright and inverted orientation. We found strong inversion effects for
      faces and houses in both the frequency of dominance epochs and their duration.
      Inversion effects for faces, however, were substantially larger, reaching a 70:30
      distribution of dominance times for upright versus inverted faces, while a 60:40
      distribution was obtained for upright versus inverted houses. Inversion effects
      for faces reached a Cohen's d of 0.85, compared to a value of 0.33 for houses.
      Dominance times for rivalry of faces against houses had a 60:40 distribution in
      favor of faces, independent of the orientation of the objects. These results
      confirm the general tendency of visual awareness to prefer upright objects, and
      demonstrate the outstanding role of faces. Since effect size measures clearly
      distinguish face stimuli in opponent-stimulus rivalry, the method is highly
      recommended for testing the effects of face manipulations against non-face
      reference objects. 

PMID- 24860478
TI  - Hybrid gait training with an overground robot for people with incomplete spinal
      cord injury: a pilot study.
AB  - Locomotor training has proved to provide beneficial effect in terms of mobility
      in incomplete paraplegic patients. Neuroprosthetic technology can contribute to
      increase the efficacy of a training paradigm in the promotion of a locomotor
      pattern. Robotic exoskeletons can be used to manage the unavoidable loss of
      performance of artificially driven muscles. Hybrid exoskeletons blend
      complementary robotic and neuro-prosthetic technologies. The aim of this pilot
      study was to determine the effects of hybrid gait training in three case studies
      with persons with incomplete spinal cord injury (iSCI) in terms of locomotion
      performance during assisted gait, patient-robot adaptations, impact on ambulation
      and assessment of lower limb muscle strength and spasticity. Participants with
      iSCI received interventions with a hybrid bilateral exoskeleton for 4 days.
      Assessment of gait function revealed that patients improved the 6 min and 10 m
      walking tests after the intervention, and further improvements were observed 1
      week after the intervention. Muscle examination revealed improvements in knee and
      hip sagittal muscle balance scores and decreased score in ankle extensor balance.
      It is concluded that improvements in biomechanical function of the knee joint
      after the tested overground hybrid gait trainer are coherent with improvements in
      gait performance. 

PMID- 24860480
TI  - The iconographic brain. A critical philosophical inquiry into (the resistance of)
      the image.
AB  - The brain image plays a central role in contemporary image culture and, in turn,
      (co)constructs contemporary forms of subjectivity. The central aim of this paper
      is to probe the unmistakably potent interpellative power of brain images by
      delving into the power of imaging and the power of the image itself. This is not
      without relevance for the neurosciences, inasmuch as these do not take place in a
      vacuum; hence the importance of inquiring into the status of the image within
      scientific culture and science itself. I will mount a critical philosophical
      investigation of the brain qua image, focusing on the issue of mapping the mental
      onto the brain and how, in turn, the brain image plays a pivotal role in
      processes of subjectivation. Hereto, I draw upon Science & Technology Studies,
      juxtaposed with culture and ideology critique and theories of image culture. The
      first section sets out from Althusser's concept of interpellation, linking
      ideology to subjectivity. Doing so allows to spell out the central question of
      the paper: what could serve as the basis for a critical approach, or, where can a
      locus of resistance be found? In the second section, drawing predominantly on
      Baudrillard, I delve into the dimension of virtuality as this is opened up by
      brain image culture. This leads to the question of whether the digital brain must
      be opposed to old analog psychology: is it the psyche which resists? This issue
      is taken up in the third section which, ultimately, concludes that the
      psychological is not the requisite locus of resistance. The fourth section
      proceeds to delineate how the brain image is constructed from what I call the
      data-gaze (the claim that brain data are always already visual). In the final
      section, I discuss how an engagement with theories of iconology affords a
      critical understanding of the interpellative force of the brain image, which
      culminates in the somewhat unexpected claim that the sought after resistance lies
      in the very status of the image itself. 

PMID- 24860479
TI  - Homuncular mirrors: misunderstanding causality in embodied cognition.

PMID- 24860481
TI  - Less Effort, Better Results: How Does Music Act on Prefrontal Cortex in Older
      Adults during Verbal Encoding? An fNIRS Study.
AB  - Several neuroimaging studies of cognitive aging revealed deficits in episodic
      memory abilities as a result of prefrontal cortex (PFC) limitations. Improving
      episodic memory performance despite PFC deficits is thus a critical issue in
      aging research. Listening to music stimulates cognitive performance in several
      non-purely musical activities (e.g., language and memory). Thus, music could
      represent a rich and helpful source during verbal encoding and therefore help
      subsequent retrieval. Furthermore, such benefit could be reflected in less demand
      of PFC, which is known to be crucial for encoding processes. This study aimed to
      investigate whether music may improve episodic memory in older adults while
      decreasing the PFC activity. Sixteen healthy older adults (MU = 64.5 years)
      encoded lists of words presented with or without a musical background while their
      dorsolateral prefrontal cortex (DLPFC) activity was monitored using a eight
      channel continuous-wave near-infrared spectroscopy (NIRS) system (Oxymon Mk III,
      Artinis, The Netherlands). Behavioral results indicated a better source-memory
      performance for words encoded with music compared to words encoded with silence
      (p < 0.05). Functional NIRS data revealed bilateral decrease of oxyhemoglobin
      values in the music encoding condition compared to the silence condition (p <
      0.05), suggesting that music modulates the activity of the DLPFC during encoding
      in a less-demanding direction. Taken together, our results indicate that music
      can help older adults in memory performances by decreasing their PFC activity.
      These findings open new perspectives about music as tool for episodic memory
      rehabilitation on special populations with memory deficits due to frontal lobe
      damage such as Alzheimer's patients. 

PMID- 24860482
TI  - An aberrant precision account of autism.
AB  - Autism is a neurodevelopmental disorder characterized by problems with social
      communication, restricted interests and repetitive behavior. A recent and thought
      provoking article presented a normative explanation for the perceptual symptoms
      of autism in terms of a failure of Bayesian inference (Pellicano and Burr, 2012).
      In response, we suggested that when Bayesian inference is grounded in its neural
      instantiation-namely, predictive coding-many features of autistic perception can
      be attributed to aberrant precision (or beliefs about precision) within the
      context of hierarchical message passing in the brain (Friston et al., 2013).
      Here, we unpack the aberrant precision account of autism. Specifically, we
      consider how empirical findings-that speak directly or indirectly to
      neurobiological mechanisms-are consistent with the aberrant encoding of precision
      in autism; in particular, an imbalance of the precision ascribed to sensory
      evidence relative to prior beliefs. 

PMID- 24860483
TI  - sLORETA intracortical lagged coherence during breath counting in meditation-naive
      participants.
AB  - We investigated brain functional connectivity comparing no-task resting to breath
      counting (a meditation exercise but given as task without referring to
      meditation). Functional connectivity computed as EEG coherence between head
      surface data suffers from localization ambiguity, reference dependence, and
      overestimation due to volume conduction. Lagged coherence between intracortical
      model sources addresses these criticisms. With this analysis approach,
      experienced meditators reportedly showed reduced coherence during meditation,
      meditation-naive participants have not yet been investigated. 58-channel EEG from
      23 healthy, right-handed, meditation-naive males during resting [3 runs] and
      breath counting [2 runs] was computed into sLORETA time series of intracortical
      electrical activity in 19 regions of interest (ROI) corresponding to the cortex
      underlying 19 scalp electrode sites, for each of the eight independent EEG
      frequency bands covering 1.5-44 Hz. Intracortical lagged coherences and head
      surface conventional coherences were computed between the 19 regions/sites.
      During breath counting compared to resting, paired t-tests corrected for multiple
      testing revealed four significantly lower intracortical lagged coherences, but
      four significantly higher head-surface conventional coherences. Lowered
      intracortical lagged coherences involved left BA 10 and right BAs 3, 10, 17, 40.
      In conclusion, intracortical lagged coherence can yield results that are inverted
      to those of head-surface conventional coherence. The lowered functional
      connectivity between cognitive control areas and sensory perception areas during
      meditation-type breath counting compared to resting conceivably reflects the
      attention to a bodily percept without cognitive reasoning. The reductions in
      functional connectivity were similar but not as widespread as the reductions
      reported during meditation in experienced meditators. 

PMID- 24860484
TI  - Spinal motor outputs during step-to-step transitions of diverse human gaits.
AB  - Aspects of human motor control can be inferred from the coordination of muscles
      during movement. For instance, by combining multimuscle electromyographic (EMG)
      recordings with human neuroanatomy, it is possible to estimate alpha-motoneuron
      (MN) pool activations along the spinal cord. It has previously been shown that
      the spinal motor output fluctuates with the body's center-of-mass motion, with
      bursts of activity around foot-strike and foot lift-off during walking. However,
      it is not known whether these MN bursts are generalizable to other ambulation
      tasks, nor is it clear if the spatial locus of the activity (along the
      rostrocaudal axis of the spinal cord) is fixed or variable. Here we sought to
      address these questions by investigating the spatiotemporal characteristics of
      the spinal motor output during various tasks: walking forward, backward, tiptoe
      and uphill. We reconstructed spinal maps from 26 leg muscle EMGs, including some
      intrinsic foot muscles. We discovered that the various walking tasks shared
      qualitative similarities in their temporal spinal activation profiles, exhibiting
      peaks around foot-strike and foot-lift. However, we also observed differences in
      the segmental level and intensity of spinal activations, particularly following
      foot-strike. For example, forward level-ground walking exhibited a mean motor
      output roughly 2 times lower than the other gaits. Finally, we found that the
      reconstruction of the spinal motor output from multimuscle EMG recordings was
      relatively insensitive to the subset of muscles analyzed. In summary, our results
      suggested temporal similarities, but spatial differences in the segmental spinal
      motor outputs during the step-to-step transitions of disparate walking behaviors.

PMID- 24860485
TI  - The time-course of EEG alpha power changes in creative ideation.
AB  - Increases in EEG alpha power during creative ideation are among the most
      consistent findings in the neuroscientific study of creativity, but existing
      studies did not focus on time-related changes of EEG alpha activity patterns
      during the process of creative ideation so far. Since several cognitive processes
      are involved in the generation of creative ideas, different EEG correlates may
      result as a function of time. In this study we addressed this crucial point.
      Forty-five participants worked on the "Alternative Uses Task" while the EEG was
      recorded and changes in task-related power (relative to rest) in the upper
      frequency band (10-12 Hz) for three isochronous time intervals of the idea
      generation period were determined. Alpha power changes during idea generation
      followed a characteristic time course: we found a general increase of alpha power
      at the beginning of idea generation that was followed by a decrease and finally
      by a re-increase of alpha prior to responding that was most pronounced at
      parietal and temporal sites of the right hemisphere. Additionally, the production
      of more original ideas was accompanied by increasing hemispheric asymmetry (more
      alpha in the right than left hemisphere) with increasing duration of the idea
      generation period. The observed time course of brain activity may reflect the
      progression of different but well-known stages in the idea generation process:
      that is the initial retrieval of common and old ideas followed by the actual
      generation of novel and more creative ideas by overcoming typical responses
      through processes of mental simulation and imagination. 

PMID- 24860486
TI  - From action intentions to action effects: how does the sense of agency come
      about?
AB  - Sense of agency refers to the feeling of controlling an external event through
      one's own action. On one influential view, agency depends on how predictable the
      consequences of one's action are, getting stronger as the match between predicted
      and actual effect of an action gets closer. Thus, sense of agency arises when
      external events that follow our action are consistent with predictions of action
      effects made by the motor system while we perform or simply intend to perform an
      action. According to this view, agency is inferred retrospectively, after an
      action has been performed and its consequences are known. In contrast, little is
      known about whether and how internal processes involved in the selection of
      actions may influence subjective sense of control, in advance of the action
      itself, and irrespective of effect predictability. In this article, we review
      several classes of behavioral and neuroimaging data suggesting that earlier
      processes, linked to fluency of action selection, prospectively contribute to
      sense of agency. These findings have important implications for better
      understanding human volition and abnormalities of action experience. 

PMID- 24860487
TI  - What future research should bring to help resolving the debate about the efficacy
      of EEG-neurofeedback in children with ADHD.
AB  - In recent years a rising amount of randomized controlled trials, reviews, and
      meta-analyses relating to the efficacy of electroencephalographic-neurofeedback
      (EEG-NF) in children with attention-deficit/hyperactivity disorder (ADHD) have
      been published. Although clinical reports and open treatment studies suggest EEG
      NF to be effective, double blind placebo-controlled studies as well as a rigorous
      meta-analysis failed to find support for the efficacy of EEG-NF. Since absence of
      evidence does not equate with evidence of absence, we will outline how future
      research might overcome the present methodological limitations. To provide
      conclusive evidence for the presence or absence of the efficacy of EEG-NF in the
      treatment of ADHD, there is a need to set up a well-designed study that ensures
      optimal implementation and embedding of the training, and possibly incorporates
      different forms of neurofeedback. 

PMID- 24860488
TI  - Towards a cross-modal perspective of emotional perception in social anxiety:
      review and future directions.
AB  - The excessive fear of being negatively evaluated constitutes a central component
      of social anxiety (SA). Models posit that selective attention to threat and
      biased interpretations of ambiguous stimuli contribute to the maintenance of this
      psychopathology. There is strong support for the existence of processing biases
      but most of the available evidence comes from face research. Emotions are,
      however, not only conveyed through facial cues, but also through other channels,
      such as vocal and postural cues. These non-facial cues have yet received much
      less attention. We therefore plead for a cross-modal investigation of biases in
      SA. We argue that the inclusion of new modalities may be an efficient research
      tool to (1) address the specificity or generalizability of these biases; (2)
      offer an insight into the potential influence of SA on cross-modal processes; (3)
      operationalize emotional ambiguity by manipulating cross-modal emotional
      congruency; (4) inform the debate about the role of top-down and bottom-up
      factors in biasing attention; and (5) probe the cross-modal generalizability of
      cognitive training. Theoretical and clinical implications as well as potential
      fruitful avenues for research are discussed. 

PMID- 24860490
TI  - Philosophical reflections on therapeutic brain stimulation.

PMID- 24860489
TI  - Effective force control by muscle synergies.
AB  - Muscle synergies have been proposed as a way for the central nervous system (CNS)
      to simplify the generation of motor commands and they have been shown to explain
      a large fraction of the variation in the muscle patterns across a variety of
      conditions. However, whether human subjects are able to control forces and
      movements effectively with a small set of synergies has not been tested directly.
      Here we show that muscle synergies can be used to generate target forces in
      multiple directions with the same accuracy achieved using individual muscles. We
      recorded electromyographic (EMG) activity from 13 arm muscles and isometric hand
      forces during a force reaching task in a virtual environment. From these data we
      estimated the force associated to each muscle by linear regression and we
      identified muscle synergies by non-negative matrix factorization. We compared
      trajectories of a virtual mass displaced by the force estimated using the entire
      set of recorded EMGs to trajectories obtained using 4-5 muscle synergies. While
      trajectories were similar, when feedback was provided according to force
      estimated from recorded EMGs (EMG-control) on average trajectories generated with
      the synergies were less accurate. However, when feedback was provided according
      to recorded force (force-control) we did not find significant differences in
      initial angle error and endpoint error. We then tested whether synergies could be
      used as effectively as individual muscles to control cursor movement in the force
      reaching task by providing feedback according to force estimated from the
      projection of the recorded EMGs into synergy space (synergy-control). Human
      subjects were able to perform the task immediately after switching from force
      control to EMG-control and synergy-control and we found no differences between
      initial movement direction errors and endpoint errors in all control modes. These
      results indicate that muscle synergies provide an effective strategy for motor
      coordination. 

PMID- 24860492
TI  - Arousal regulation and affective adaptation to human responsiveness by a robot
      that explores and learns a novel environment.
AB  - In the context of our work in developmental robotics regarding robot-human
      caregiver interactions, in this paper we investigate how a "baby" robot that
      explores and learns novel environments can adapt its affective regulatory
      behavior of soliciting help from a "caregiver" to the preferences shown by the
      caregiver in terms of varying responsiveness. We build on two strands of previous
      work that assessed independently (a) the differences between two "idealized"
      robot profiles-a "needy" and an "independent" robot-in terms of their use of a
      caregiver as a means to regulate the "stress" (arousal) produced by the
      exploration and learning of a novel environment, and (b) the effects on the robot
      behaviors of two caregiving profiles varying in their responsiveness-"responsive"
      and "non-responsive"-to the regulatory requests of the robot. Going beyond
      previous work, in this paper we (a) assess the effects that the varying
      regulatory behavior of the two robot profiles has on the exploratory and learning
      patterns of the robots; (b) bring together the two strands previously
      investigated in isolation and take a step further by endowing the robot with the
      capability to adapt its regulatory behavior along the "needy" and "independent"
      axis as a function of the varying responsiveness of the caregiver; and (c)
      analyze the effects that the varying regulatory behavior has on the exploratory
      and learning patterns of the adaptive robot. 

PMID- 24860491
TI  - A non-linear dynamical approach to belief revision in cognitive behavioral
      therapy.
AB  - Belief revision is the key change mechanism underlying the psychological
      intervention known as cognitive behavioral therapy (CBT). It both motivates and
      reinforces new behavior. In this review we analyze and apply a novel approach to
      this process based on AGM theory of belief revision, named after its proponents,
      Carlos Alchourron, Peter Gardenfors and David Makinson. AGM is a set-theoretical
      model. We reconceptualize it as describing a non-linear, dynamical system that
      occurs within a semantic space, which can be represented as a phase plane
      comprising all of the brain's attentional, cognitive, affective and physiological
      resources. Triggering events, such as anxiety-producing or depressing situations
      in the real world, or their imaginal equivalents, mobilize these assets so they
      converge on an equilibrium point. A preference function then evaluates and
      integrates evidentiary data associated with individual beliefs, selecting some of
      them and comprising them into a belief set, which is a metastable state. Belief
      sets evolve in time from one metastable state to another. In the phase space,
      this evolution creates a heteroclinic channel. AGM regulates this process and
      characterizes the outcome at each equilibrium point. Its objective is to define
      the necessary and sufficient conditions for belief revision by simultaneously
      minimizing the set of new beliefs that have to be adopted, and the set of old
      beliefs that have to be discarded or reformulated. Using AGM, belief revision can
      be modeled using three (and only three) fundamental syntactical operations
      performed on belief sets, which are expansion; revision; and contraction.
      Expansion is like adding a new belief without changing any old ones. Revision is
      like adding a new belief and changing old, inconsistent ones. Contraction is like
      changing an old belief without adding any new ones. We provide operationalized
      examples of this process in action. 

PMID- 24860493
TI  - Anti-inflammatory polymer electrodes for glial scar treatment: bringing the
      conceptual idea to future results.
AB  - Conducting polymer films offer a convenient route for the functionalization of
      implantable microelectrodes without compromising their performance as excellent
      recording units. A micron thick coating, deposited on the surface of a regular
      metallic electrode, can elute anti-inflammatory drugs for the treatment of glial
      scarring as well as growth factors for the support of surrounding neurons.
      Electro-activation of the polymer drives the release of the substance and should
      ideally provide a reliable method for controlling quantity and timing of release.
      Driving signals in the form of a constant potential (CP), a slow redox sweep or a
      fast pulse are all represented in literature. Few studies present such release in
      vivo from actual recording and stimulating microelectronic devices. It is
      essential to bridge the gap between studies based on release in vitro, and the
      intended application, which would mean release into living and highly delicate
      tissue. In the biological setting, signals are limited both by available
      electronics and by the biological safety. Driving signals must not be harmful to
      tissue and also not activate the tissue in an uncontrolled manner. This review
      aims at shedding more light on how to select appropriate driving parameters for
      the polymer electrodes for the in vivo setting. It brings together information
      regarding activation thresholds for neurons, as well as injury thresholds, and
      puts this into context with what is known about efficient driving of release from
      conducting polymer films. 

PMID- 24860494
TI  - Tai Chi Chuan optimizes the functional organization of the intrinsic human brain
      architecture in older adults.
AB  - Whether Tai Chi Chuan (TCC) can influence the intrinsic functional architecture
      of the human brain remains unclear. To examine TCC-associated changes in
      functional connectomes, resting-state functional magnetic resonance images were
      acquired from 40 older individuals including 22 experienced TCC practitioners
      (experts) and 18 demographically matched TCC-naive healthy controls, and their
      local functional homogeneities across the cortical mantle were compared. Compared
      to the controls, the TCC experts had significantly greater and more experience
      dependent functional homogeneity in the right post-central gyrus (PosCG) and less
      functional homogeneity in the left anterior cingulate cortex (ACC) and the right
      dorsal lateral prefrontal cortex. Increased functional homogeneity in the PosCG
      was correlated with TCC experience. Intriguingly, decreases in functional
      homogeneity (improved functional specialization) in the left ACC and increases in
      functional homogeneity (improved functional integration) in the right PosCG both
      predicted performance gains on attention network behavior tests. These findings
      provide evidence for the functional plasticity of the brain's intrinsic
      architecture toward optimizing locally functional organization, with great
      implications for understanding the effects of TCC on cognition, behavior and
      health in aging population. 

PMID- 24860496
TI  - Mental health and dual sensory loss in older adults: a systematic review.
AB  - Mental health is a core component of quality of life in old age. Dual Sensory
      Loss (DSL; combined vision and hearing loss) is prevalent in older adults and has
      been correlated with decreased levels of well-being. This systematic review aimed
      to critically review and summarize the evidence from studies that examined the
      mental health of older adults with DSL. In accordance with the Preferred
      Reporting Items for Systematic Reviews (PRISMA) statement, specific databases
      were searched and eight articles were selected for final review. Seven studies
      investigated the association between DSL and depression or depressive symptoms,
      whilst one study explored the relationship between DSL and quality of life. No
      studies investigated the impact of DSL on anxiety. Overall, results of this
      review suggested that there is a significant relationship between DSL and
      decreased mental health with those with DSL either displaying depressive symptoms
      or being at risk for developing depression. Future research should focus on
      comparative studies of older people with and without sensory loss, as well as
      targeted studies of older people with dual sensory loss, that incorporate well
      defined and valid measures of sensory loss and mental health. 

PMID- 24860497
TI  - The drive-wise project: driving simulator training increases real driving
      performance in healthy older drivers.
AB  - BACKGROUND: Age-related cognitive decline is often associated with unsafe driving
      behavior. We hypothesized that 10 active training sessions in a driving simulator
      increase cognitive and on-road driving performance. In addition, driving
      simulator training should outperform cognitive training. METHODS: Ninety-one
      healthy active drivers (62-87 years) were randomly assigned to one of three
      groups: (1) a driving simulator training group, (2) an attention training group
      (vigilance and selective attention), or (3) a control group. The main outcome
      variables were on-road driving and cognitive performance. Seventy-seven
      participants (85%) completed the training and were included in the analyses.
      Training gains were analyzed using a multiple regression analysis with planned
      orthogonal comparisons. RESULTS: The driving simulator-training group showed an
      improvement in on-road driving performance compared to the attention-training
      group. In addition, both training groups increased cognitive performance compared
      to the control group. CONCLUSION: Driving simulator training offers the potential
      to enhance driving skills in older drivers. Compared to the attention training,
      the simulator training seems to be a more powerful program for increasing older
      drivers' safety on the road.

PMID- 24860498
TI  - Involvement of dopamine loss in extrastriatal basal ganglia nuclei in the
      pathophysiology of Parkinson's disease.
AB  - Parkinson's disease (PD) is a neurological disorder characterized by the
      manifestation of motor symptoms, such as akinesia, muscle rigidity and tremor at
      rest. These symptoms are classically attributed to the degeneration of dopamine
      neurons in the pars compacta of substantia nigra (SNc), which results in a marked
      dopamine depletion in the striatum. It is well established that dopamine neurons
      in the SNc innervate not only the striatum, which is the main target, but also
      other basal ganglia nuclei including the two segments of globus pallidus and the
      subthalamic nucleus (STN). The role of dopamine and its depletion in the striatum
      is well known, however, the role of dopamine depletion in the pallidal complex
      and the STN in the genesis of their abnormal neuronal activity and in
      parkinsonian motor deficits is still not clearly determined. Based on recent
      experimental data from animal models of Parkinson's disease in rodents and non
      human primates and also from parkinsonian patients, this review summarizes
      current knowledge on the role of dopamine in the modulation of basal ganglia
      neuronal activity and also the role of dopamine depletion in these nuclei in the
      pathophysiology of Parkinson's disease. 

PMID- 24860495
TI  - The role of intracellular zinc release in aging, oxidative stress, and
      Alzheimer's disease.
AB  - Brain aging is marked by structural, chemical, and genetic changes leading to
      cognitive decline and impaired neural functioning. Further, aging itself is also
      a risk factor for a number of neurodegenerative disorders, most notably
      Alzheimer's disease (AD). Many of the pathological changes associated with aging
      and aging-related disorders have been attributed in part to increased and
      unregulated production of reactive oxygen species (ROS) in the brain. ROS are
      produced as a physiological byproduct of various cellular processes, and are
      normally detoxified by enzymes and antioxidants to help maintain neuronal
      homeostasis. However, cellular injury can cause excessive ROS production,
      triggering a state of oxidative stress that can lead to neuronal cell death. ROS
      and intracellular zinc are intimately related, as ROS production can lead to
      oxidation of proteins that normally bind the metal, thereby causing the
      liberation of zinc in cytoplasmic compartments. Similarly, not only can zinc
      impair mitochondrial function, leading to excess ROS production, but it can also
      activate a variety of extra-mitochondrial ROS-generating signaling cascades. As
      such, numerous accounts of oxidative neuronal injury by ROS-producing sources
      appear to also require zinc. We suggest that zinc deregulation is a common,
      perhaps ubiquitous component of injurious oxidative processes in neurons. This
      review summarizes current findings on zinc dyshomeostasis-driven signaling
      cascades in oxidative stress and age-related neurodegeneration, with a focus on
      AD, in order to highlight the critical role of the intracellular liberation of
      the metal during oxidative neuronal injury. 

PMID- 24860499
TI  - Myogenic potential of canine craniofacial satellite cells.
AB  - The skeletal fibers have different embryological origin; the extraocular and jaw
      closer muscles develop from prechordal mesoderm while the limb and trunk muscles
      from somites. These different origins characterize also the adult muscle stem
      cells, known as satellite cells (SCs) and responsible for the fiber growth and
      regeneration. The physiological properties of presomitic SCs and their
      epigenetics are poorly studied despite their peculiar characteristics to preserve
      muscle integrity during chronic muscle degeneration. Here, we isolated SCs from
      canine somitic [somite-derived muscle (SDM): vastus lateralis, rectus abdominis,
      gluteus superficialis, biceps femoris, psoas] and presomitic [pre-somite-derived
      muscle (PSDM): lateral rectus, temporalis, and retractor bulbi] muscles as
      myogenic progenitor cells from young and old animals. In addition, SDM and PSDM
      SCs were obtained also from golden retrievers affected by muscular dystrophy
      (GRMD). We characterized the lifespan, the myogenic potential and functions, and
      oxidative stress of both somitic and presomitic SCs with the aim to reveal
      differences with aging and between healthy and dystrophic animals. The different
      proliferation rate was consistent with higher telomerase activity in PSDM-SCs
      compared to SDM-SCs, although restricted at early passages. SDM-SCs express early
      (Pax7, MyoD) and late (myosin heavy chain, myogenin) myogenic markers differently
      from PSDM-SCs resulting in a more efficient and faster cell differentiation.
      Taken together, our results showed that PSDM-SCs elicit a stronger stem cell
      phenotype compared to SDM ones. Finally, myomiR expression profile reveals a
      unique epigenetic signature in GRMD SCs and miR-206, highly expressed in
      dystrophic SCs, seems to play a critical role in muscle degeneration. Thus, miR
      206 could represent a potential target for novel therapeutic approaches. 

PMID- 24860501
TI  - Alzheimer's disease causation by copper toxicity and treatment with zinc.
AB  - Evidence will be presented that the Alzheimer's disease (AD) epidemic is new, the
      disease being very rare in the 1900s. The incidence is increasing rapidly, but
      only in developed countries. We postulate that the new emerging environmental
      factor partially causal of the AD epidemic is ingestion of inorganic copper from
      drinking water and taking supplement pills, along with a high fat diet. Inorganic
      copper can be partially directly absorbed and elevate the serum free copper pool.
      The Squitti group has shown that serum free copper is elevated in AD, correlates
      with cognition, and predicts cognition loss. Thus, our inorganic copper
      hypothesis fits well with the Squitti group data. We have also shown that AD
      patients are zinc deficient compared to age-matched controls. Because zinc is a
      neuronal protective factor, we postulate that zinc deficiency may also be
      partially causative of AD. We carried out a small 6 month double blind study of a
      new zinc formulation and found that in patients age 70 and over, it protected
      against cognition loss. Zinc therapy also significantly reduced serum free copper
      in AD patients, so efficacy may come from restoring normal zinc levels, or from
      lowering serum free copper, or from both. 

PMID- 24860502
TI  - Resveratrol and Alzheimer's disease: message in a bottle on red wine and
      cognition.
AB  - Cognitive impairment is the final outcome of a complex network of molecular
      mechanisms ultimately leading to dementia. Despite major efforts aimed at
      unraveling the molecular determinants of dementia of Alzheimer type (DAT),
      effective disease-modifying approaches are still missing. An interesting and
      still largely unexplored avenue is offered by nutraceutical intervention. For
      instance, robust epidemiological data have suggested that moderate intake of red
      wine may protect against several age-related pathological conditions (i.e.,
      cardiovascular diseases, diabetes, and cancer) as well as DAT-related cognitive
      decline. Wine is highly enriched in many polyphenols, including resveratrol.
      Resveratrol is a well recognized antioxidant which may modulate metal ion
      deregulation outcomes as well as main features of the Alzheimer's disease (AD)
      brain. The review will discuss the potentiality of resveratrol as a
      neuroprotectant in dementia in relation to the oxidative stress produced by
      amyloid and metal dysmetabolism. 

PMID- 24860503
TI  - H-ferritin ferroxidase induces cytoprotective pathways and inhibits microvascular
      stasis in transgenic sickle mice.
AB  - Hemolysis, oxidative stress, inflammation, vaso-occlusion, and organ infarction
      are hallmarks of sickle cell disease (SCD). We have previously shown that
      increases in heme oxygenase-1 (HO-1) activity detoxify heme and inhibit vaso
      occlusion in transgenic mouse models of SCD. HO-1 releases Fe(2+) from heme, and
      the ferritin heavy chain (FHC) ferroxidase oxidizes Fe(2+) to catalytically
      inactive Fe(3+) inside ferritin. FHC overexpression has been shown to be
      cytoprotective. In this study, we hypothesized that overexpression of FHC and its
      ferroxidase activity will inhibit inflammation and microvascular stasis in
      transgenic SCD mice in response to plasma hemoglobin. We utilized a Sleeping
      Beauty (SB) transposase plasmid to deliver a human wild-type-ferritin heavy chain
      (wt-hFHC) transposable element by hydrodynamic tail vein injections into NY1DD
      SCD mice. Control SCD mice were infused with the same volume of lactated Ringer's
      solution (LRS) or a human triple missense FHC (ms-hFHC) plasmid with no
      ferroxidase activity. 8 weeks later, LRS-injected mice had ~40% microvascular
      stasis (% non-flowing venules) 1 h after infusion of stroma-free hemoglobin,
      while mice overexpressing wt-hFHC had only 5% stasis (p < 0.05), and ms-hFHC mice
      had 33% stasis suggesting vascular protection by ferroxidase active wt-hFHC. The
      wt-hFHC SCD mice had marked increases in splenic hFHC mRNA and hepatic hFHC
      protein, ferritin light chain (FLC), 5-aminolevulinic acid synthase (ALAS), heme
      content, ferroportin, nuclear factor erythroid 2-related factor 2 (Nrf2), and HO
      1 activity and protein. There was also a decrease in hepatic activated nuclear
      factor-kappa B (NF-kappaB) phospho-p65 and vascular cell adhesion molecule-1
      (VCAM-1). Inhibition of HO-1 activity with tin protoporphyrin demonstrated HO-1
      was not essential for the protection by wt-hFHC. We conclude that wt-hFHC
      ferroxidase activity enhances cytoprotective Nrf2-regulated proteins including HO
      1, thereby resulting in decreased NF-kappaB-activation, adhesion molecules, and
      microvascular stasis in transgenic SCD mice. 

PMID- 24860504
TI  - Sirtuin modulators control reactive gliosis in an in vitro model of Alzheimer's
      disease.
AB  - Among neurodegenerative disorders, Alzheimer's disease (AD) represents the most
      common cause of dementia in the elderly. Several genetic and environmental
      factors have been identified; however, aging represents the most important risk
      factor in the development of AD. To date, no effective treatments to prevent or
      slow this dementia are available. Sirtuins (SIRTs) are a family of NAD(+)
      dependent enzymes, implicated in the control of a variety of biological processes
      that have the potential to modulate neurodegeneration. Here we tested the
      hypothesis that activation of SIRT1 or inhibition of SIRT2 would prevent reactive
      gliosis which is considered one of the most important hallmark of AD. Primary rat
      astrocytes were activated with beta amyloid 1-42 (Abeta 1-42) and treated with
      resveratrol (RSV) or AGK-2, a SIRT1 activator and a SIRT2-selective inhibitor,
      respectively. Results showed that both RSV and AGK-2 were able to reduce
      astrocyte activation as well as the production of pro-inflammatory mediators.
      These data disclose novel findings about the therapeutic potential of SIRT
      modulators, and suggest novel strategies for AD treatment. 

PMID- 24860500
TI  - Metals and cholesterol: two sides of the same coin in Alzheimer's disease
      pathology.
AB  - Alzheimer's disease (AD) is a multifactorial neurodegenerative disease. It begins
      years prior to the onset of clinical symptoms, such as memory loss and cognitive
      decline. Pathological hallmarks of AD include the accumulation of beta-amyloid in
      plaques and hyperphosphorylated tau in neurofibrillary tangles. Copper, iron, and
      zinc are abnormally accumulated and distributed in the aging brain. These metal
      ions can adversely contribute to the progression of AD. Dysregulation of
      cholesterol metabolism has also been implicated in the development of AD
      pathology. To date, large bodies of research have been carried out independently
      to elucidate the role of metals or cholesterol on AD pathology. Interestingly,
      metals and cholesterol affect parallel molecular and biochemical pathways
      involved in AD pathology. The possible links between metal dyshomeostasis and
      altered brain cholesterol metabolism in AD are reviewed. 

PMID- 24860507
TI  - Optogenetics to help exploring the cerebral blood flow regulation.

PMID- 24860505
TI  - Hemojuvelin and bone morphogenetic protein (BMP) signaling in iron homeostasis.
AB  - Mutations in hemojuvelin (HJV) are the most common cause of the juvenile-onset
      form of the iron overload disorder hereditary hemochromatosis. The discovery that
      HJV functions as a co-receptor for the bone morphogenetic protein (BMP) family of
      signaling molecules helped to identify this signaling pathway as a central
      regulator of the key iron hormone hepcidin in the control of systemic iron
      homeostasis. This review highlights recent work uncovering the mechanism of
      action of HJV and the BMP-SMAD signaling pathway in regulating hepcidin
      expression in the liver, as well as additional studies investigating possible
      extra-hepatic functions of HJV. This review also explores the interaction between
      HJV, the BMP-SMAD signaling pathway and other regulators of hepcidin expression
      in systemic iron balance. 

PMID- 24860506
TI  - Challenges and future prospects of antibiotic therapy: from peptides to phages
      utilization.
AB  - Bacterial infections are raising serious concern across the globe. The
      effectiveness of conventional antibiotics is decreasing due to global emergence
      of multi-drug-resistant (MDR) bacterial pathogens. This process seems to be
      primarily caused by an indiscriminate and inappropriate use of antibiotics in non
      infected patients and in the food industry. New classes of antibiotics with
      different actions against MDR pathogens need to be developed urgently. In this
      context, this review focuses on several ways and future directions to search for
      the next generation of safe and effective antibiotics compounds including
      antimicrobial peptides, phage therapy, phytochemicals, metalloantibiotics,
      lipopolysaccharide, and efflux pump inhibitors to control the infections caused
      by MDR pathogens. 

PMID- 24860508
TI  - Evaluation and integration of disparate classification systems for clefts of the
      lip.
AB  - Orofacial clefting is a common birth defect with wide phenotypic variability.
      Many systems have been developed to classify cleft patterns to facilitate
      diagnosis, management, surgical treatment, and research. In this review, we
      examine the rationale for different existing classification schemes and determine
      their inter-relationships, as well as strengths and deficiencies for
      subclassification of clefts of the lip. The various systems differ in how they
      describe and define attributes of cleft lip (CL) phenotypes. Application and
      analysis of the CL classifications reveal discrepancies that may result in errors
      when comparing studies that use different systems. These inconsistencies in
      terminology, variable levels of subclassification, and ambiguity in some
      descriptions may confound analyses and impede further research aimed at
      understanding the genetics and etiology of clefts, development of effective
      treatment options for patients, as well as cross-institutional comparisons of
      outcome measures. Identification and reconciliation of discrepancies among
      existing systems is the first step toward creating a common standard to allow for
      a more explicit interpretation that will ultimately lead to a better
      understanding of the causes and manifestations of phenotypic variations in
      clefting. 

PMID- 24860509
TI  - Timing matters: sonar call groups facilitate target localization in bats.
AB  - To successfully negotiate a cluttered environment, an echolocating bat must
      control the timing of motor behaviors in response to dynamic sensory information.
      Here we detail the big brown bat's adaptive temporal control over sonar call
      production for tracking prey, moving predictably or unpredictably, under
      different experimental conditions. We studied the adaptive control of vocal-motor
      behaviors in free-flying big brown bats, Eptesicus fuscus, as they captured
      tethered and free-flying insects, in open and cluttered environments. We also
      studied adaptive sonar behavior in bats trained to track moving targets from a
      resting position. In each of these experiments, bats adjusted the features of
      their calls to separate target and clutter. Under many task conditions, flying
      bats produced prominent sonar sound groups identified as clusters of echolocation
      pulses with relatively stable intervals, surrounded by longer pulse intervals. In
      experiments where bats tracked approaching targets from a resting position, bats
      also produced sonar sound groups, and the prevalence of these sonar sound groups
      increased when motion of the target was unpredictable. We hypothesize that sonar
      sound groups produced during flight, and the sonar call doublets produced by a
      bat tracking a target from a resting position, help the animal resolve dynamic
      target location and represent the echo scene in greater detail. Collectively, our
      data reveal adaptive temporal control over sonar call production that allows the
      bat to negotiate a complex and dynamic environment. 

PMID- 24860510
TI  - Wavelet-based multifractal analysis of dynamic infrared thermograms to assist in
      early breast cancer diagnosis.
AB  - Breast cancer is the most common type of cancer among women and despite recent
      advances in the medical field, there are still some inherent limitations in the
      currently used screening techniques. The radiological interpretation of screening
      X-ray mammograms often leads to over-diagnosis and, as a consequence, to
      unnecessary traumatic and painful biopsies. Here we propose a computer-aided
      multifractal analysis of dynamic infrared (IR) imaging as an efficient method for
      identifying women with risk of breast cancer. Using a wavelet-based multi-scale
      method to analyze the temporal fluctuations of breast skin temperature collected
      from a panel of patients with diagnosed breast cancer and some female volunteers
      with healthy breasts, we show that the multifractal complexity of temperature
      fluctuations observed in healthy breasts is lost in mammary glands with malignant
      tumor. Besides potential clinical impact, these results open new perspectives in
      the investigation of physiological changes that may precede anatomical
      alterations in breast cancer development. 

PMID- 24860513
TI  - Effects of bright light treatment on psychomotor speed in athletes.
AB  - PURPOSE: A recent study suggests that transcranial brain targeted light treatment
      via ear canals may have physiological effects on brain function studied by
      functional magnetic resonance imaging (fMRI) techniques in humans. We tested the
      hypothesis that bright light treatment could improve psychomotor speed in
      professional ice hockey players. METHODS: Psychomotor speed tests with audio and
      visual warning signals were administered to a Finnish National Ice Hockey League
      team before and after 24 days of transcranial bright light or sham treatment. The
      treatments were given during seasonal darkness in the Oulu region (latitude 65
      degrees north) when the strain on the players was also very high (10 matches
      during 24 days). A daily 12-min dose of bright light or sham (n = 11 for both)
      treatment was given every morning between 8 and 12 am at home with a transcranial
      bright light device. Mean reaction time and motor time were analyzed separately
      for both psychomotor tests. Analysis of variance for repeated measures adjusted
      for age was performed. RESULTS: Time * group interaction for motor time with a
      visual warning signal was p = 0.024 after adjustment for age. In Bonferroni post
      hoc analysis, motor time with a visual warning signal decreased in the bright
      light treatment group from 127 +/- 43 to 94 +/- 26 ms (p = 0.024) but did not
      change significantly in the sham group 121 +/- 23 vs. 110 +/- 32 ms (p = 0.308).
      Reaction time with a visual signal did not change in either group. Reaction or
      motor time with an audio warning signal did not change in either the treatment or
      sham group. CONCLUSION: Psychomotor speed, particularly motor time with a visual
      warning signal, improves after transcranial bright light treatment in
      professional ice-hockey players during the competition season in the dark time of
      the year.

PMID- 24860512
TI  - Vitamin D, intermediary metabolism and prostate cancer tumor progression.
AB  - Epidemiological data have demonstrated an inverse association between serum
      vitamin D3 levels, cancer incidence and related mortality. However, the effects
      of vitamin D on prostate cancer biology and its utility for prevention of
      prostate cancer progression are not as well-defined. The data are often
      conflicting: some reports suggest that vitamin D3 induces apoptosis in androgen
      dependent prostate cancer cell lines, while others suggest that vitamin D3 only
      induces cell cycle arrest. Recent molecular studies have identified an extensive
      synergistic crosstalk between the vitamin D- and androgen-mediated mRNA and miRNA
      expression, adding an additional layer of post-transcriptional regulation to the
      known VDR- and AR-regulated gene activation. The Warburg effect, the inefficient
      metabolic pathway that converts glucose to lactate for rapid energy generation,
      is a phenomenon common to many different types of cancer. This process supports
      cell proliferation and promotes cancer progression via alteration of glucose,
      glutamine and lipid metabolism. Prostate cancer is a notable exception to this
      general process since the metabolic switch that occurs early during malignancy is
      the reverse of the Warburg effect. This "anti-Warburg effect" is due to the
      unique biology of normal prostate cells that harbor a truncated TCA cycle that is
      required to produce and secret citrate. In prostate cancer cells, the TCA cycle
      activity is restored and citrate oxidation is used to produce energy for cancer
      cell proliferation. 1,25(OH)2D3 and androgen together modulates the TCA cycle via
      transcriptional regulation of zinc transporters, suggesting that 1,25(OH)2D3 and
      androgen maintain normal prostate metabolism by blocking citrate oxidation. These
      data demonstrate the importance of androgens in the anti-proliferative effect of
      vitamin D in prostate cancer and highlight the importance of understanding the
      crosstalk between these two signaling pathways. 

PMID- 24860515
TI  - A longitudinal multilevel CFA-MTMM model for interchangeable and structurally
      different methods.
AB  - One of the key interests in the social sciences is the investigation of change
      and stability of a given attribute. Although numerous models have been proposed
      in the past for analyzing longitudinal data including multilevel and/or latent
      variable modeling approaches, only few modeling approaches have been developed
      for studying the construct validity in longitudinal multitrait-multimethod (MTMM)
      measurement designs. The aim of the present study was to extend the spectrum of
      current longitudinal modeling approaches for MTMM analysis. Specifically, a new
      longitudinal multilevel CFA-MTMM model for measurement designs with structurally
      different and interchangeable methods (called Latent-State-Combination-Of-Methods
      model, LS-COM) is presented. Interchangeable methods are methods that are
      randomly sampled from a set of equivalent methods (e.g., multiple student ratings
      for teaching quality), whereas structurally different methods are methods that
      cannot be easily replaced by one another (e.g., teacher, self-ratings, principle
      ratings). Results of a simulation study indicate that the parameters and standard
      errors in the LS-COM model are well recovered even in conditions with only five
      observations per estimated model parameter. The advantages and limitations of the
      LS-COM model relative to other longitudinal MTMM modeling approaches are
      discussed. 

PMID- 24860511
TI  - Vitamin D and the RNA transcriptome: more than mRNA regulation.
AB  - The GRCh37.p13 primary assembly of the human genome contains 20805 protein coding
      mRNA, and 37147 non-protein coding genes and pseudogenes that as a result of RNA
      processing and editing generate 196501 gene transcripts. Given the size and
      diversity of the human transcriptome, it is timely to revisit what is known of
      VDR function in the regulation and targeting of transcription. Early
      transcriptomic studies using microarray approaches focused on the protein coding
      mRNA that were regulated by the VDR, usually following treatment with ligand.
      These studies quickly established the approximate size, and surprising diversity
      of the VDR transcriptome, revealing it to be highly heterogenous and cell type
      and time dependent. With the discovery of microRNA, investigators also considered
      VDR regulation of these non-protein coding RNA. Again, cell and time dependency
      has emerged. Attempts to integrate mRNA and miRNA regulation patterns are
      beginning to reveal patterns of co-regulation and interaction that allow for
      greater control of mRNA expression, and the capacity to govern more complex
      cellular events. As the awareness of the diversity of non-coding RNA increases,
      it is increasingly likely it will be revealed that VDR actions are mediated
      through these molecules also. Key knowledge gaps remain over the VDR
      transcriptome. The causes for the cell and type dependent transcriptional
      heterogenetiy remain enigmatic. ChIP-Seq approaches have confirmed that VDR
      binding choices differ very significantly by cell type, but as yet the underlying
      causes distilling VDR binding choices are unclear. Similarly, it is clear that
      many of the VDR binding sites are non-canonical in nature but again the
      mechanisms underlying these interactions are unclear. Finally, although
      alternative splicing is clearly a very significant process in cellular
      transcriptional control, the lack of RNA-Seq data centered on VDR function are
      currently limiting the global assessment of the VDR transcriptome. VDR focused
      research that complements publically available data (e.g., ENCODE Birney et al.,
      2007; Birney, 2012), TCGA (Strausberg et al., 2002), GTEx (Consortium, 2013) will
      enable these questions to be addressed through large-scale data integration
      efforts. 

PMID- 24860514
TI  - Gene-environment interactions in severe mental illness.
AB  - Severe mental illness (SMI) is a broad category that includes schizophrenia,
      bipolar disorder, and severe depression. Both genetic disposition and
      environmental exposures play important roles in the development of SMI. Multiple
      lines of evidence suggest that the roles of genetic and environmental factors
      depend on each other. Gene-environment interactions may underlie the paradox of
      strong environmental factors for highly heritable disorders, the low estimates of
      shared environmental influences in twin studies of SMI, and the heritability gap
      between twin and molecular heritability estimates. Sons and daughters of parents
      with SMI are more vulnerable to the effects of prenatal and postnatal
      environmental exposures, suggesting that the expression of genetic liability
      depends on environment. In the last decade, gene-environment interactions
      involving specific molecular variants in candidate genes have been identified.
      Replicated findings include an interaction between a polymorphism in the AKT1
      gene and cannabis use in the development of psychosis and an interaction between
      the length polymorphism of the serotonin transporter gene and childhood
      maltreatment in the development of persistent depressive disorder. Bipolar
      disorder has been underinvestigated, with only a single study showing an
      interaction between a functional polymorphism in the BDNF gene and stressful life
      events triggering bipolar depressive episodes. The first systematic search for
      gene-environment interactions has found that a polymorphism in CTNNA3 may
      sensitize the developing brain to the pathogenic effect of cytomegalovirus in
      utero, leading to schizophrenia in adulthood. Strategies for genome-wide
      investigations will likely include coordination between epidemiological and
      genetic research efforts, systematic assessment of multiple environmental factors
      in large samples, and prioritization of genetic variants. 

PMID- 24860516
TI  - New normative standards of conditional reasoning and the dual-source model.
AB  - There has been a major shift in research on human reasoning toward Bayesian and
      probabilistic approaches, which has been called a new paradigm. The new paradigm
      sees most everyday and scientific reasoning as taking place in a context of
      uncertainty, and inference is from uncertain beliefs and not from arbitrary
      assumptions. In this manuscript we present an empirical test of normative
      standards in the new paradigm using a novel probabilized conditional reasoning
      task. Our results indicated that for everyday conditional with at least a weak
      causal connection between antecedent and consequent only the conditional
      probability of the consequent given antecedent contributes unique variance to
      predicting the probability of conditional, but not the probability of the
      conjunction, nor the probability of the material conditional. Regarding normative
      accounts of reasoning, we found significant evidence that participants' responses
      were confidence preserving (i.e., p-valid in the sense of Adams, 1998) for MP
      inferences, but not for MT inferences. Additionally, only for MP inferences and
      to a lesser degree for DA inferences did the rate of responses inside the
      coherence intervals defined by mental probability logic (Pfeifer and Kleiter,
      2005, 2010) exceed chance levels. In contrast to the normative accounts, the dual
      source model (Klauer et al., 2010) is a descriptive model. It posits that
      participants integrate their background knowledge (i.e., the type of information
      primary to the normative approaches) and their subjective probability that a
      conclusion is seen as warranted based on its logical form. Model fits showed that
      the dual-source model, which employed participants' responses to a deductive task
      with abstract contents to estimate the form-based component, provided as good an
      account of the data as a model that solely used data from the probabilized
      conditional reasoning task. 

PMID- 24860517
TI  - The quest for knowledge transfer efficacy: blended teaching, online and in-class,
      with consideration of learning typologies for non-traditional and traditional
      students.
AB  - The pedagogical paradigm shift in higher education to 24-h learning environments
      composed of teaching delivery methods of online courses, blended/hybrid formats,
      and face-to-face (f2f) classes is increasing access to global, lifelong learning.
      Online degrees have been offered at 62.4% of 2800 colleges and universities.
      Students can now design flexible, life-balanced course schedules. Higher
      knowledge transfer rates may exist with blended course formats with online
      quizzes and valuable class time set for Socratic, quality discussions and
      creative team presentations. Research indicates that younger, traditional
      students exhibit heightened performance goal orientations and prefer entertaining
      professors who are funny, whereas non-traditional students exhibit mastery
      profiles and prefer courses taught by flexible, yet organized, professors. A 5
      year study found that amongst 51,000 students taking both f2f and online courses,
      higher online failure rates occurred. Competing life roles for non-traditional
      students and reading and writing needs for at-risk students suggest that
      performance may be better if programs are started in f2f courses. Models on
      effective knowledge transfer consider the planning process, delivery methods, and
      workplace application, but a gap exists for identifying the diversity of learner
      needs. Higher education enrollments are being compromised with lower online
      retention rates. Therefore, the main purpose of this review is to delineate
      disparate learning styles and present a typology for the learning needs of
      traditional and non-traditional students. Secondly, psychology as a science may
      need more rigorous curriculum markers like mapping APA guidelines to knowledge
      objectives, critical assignments, and student learning outcomes (SLOs) (e.g.,
      online rubric assessments for scoring APA style critical thinking essays on
      selected New York Times books). Efficacious knowledge transfer to diverse, 21st
      century students should be the Academy's focus. 

PMID- 24860518
TI  - Naturalistic acquisition in an early language classroom.
AB  - This study investigated whether it is possible to provide naturalistic second
      language acquisition (SLA) of vocabulary for young learners in a classroom
      situation without resorting to a classical immersion approach. Participants were
      60 first-grade pupils in two Norwegian elementary schools in their first year.
      The control group followed regular instruction as prescribed by the school
      curriculum, while the experimental group received increased naturalistic target
      language input. This entailed extensive use of English by the teacher during
      English classes, and also during morning meetings and for simple instructions and
      classroom management throughout the day. Our hypothesis was that it is possible
      to facilitate naturalistic acquisition through better quality target language
      exposure within a normal curriculum. The students' English vocabulary knowledge
      was measured using the Peabody Picture Vocabulary Test, version 4 (PPVT-IV, Dunn
      and Dunn, 2007a), at the beginning and the end of the first year of school.
      Findings are that (1) early-start second-language (L2) programs in school do not
      in themselves guarantee vocabulary development in the first year, (2) a focus on
      increased exposure to the L2 can lead to a significant increase in receptive
      vocabulary comprehension in the course of only 8 months, and (3) even with
      relatively modest input, learners in such an early-start L2 program can display
      vocabulary acquisition comparable in some respects to that of younger native
      children matched on vocabulary size. The overall conclusion is that naturalistic
      vocabulary acquisition is in fact possible in a classroom setting. 

PMID- 24860519
TI  - Normativity, interpretation, and Bayesian models.
AB  - It has been suggested that evaluative normativity should be expunged from the
      psychology of reasoning. A broadly Davidsonian response to these arguments is
      presented. It is suggested that two distinctions, between different types of
      rationality, are more permeable than this argument requires and that the
      fundamental objection is to selecting theories that make the most rational sense
      of the data. It is argued that this is inevitable consequence of radical
      interpretation where understanding others requires assuming they share our own
      norms of reasoning. This requires evaluative normativity and it is shown that
      when asked to evaluate others' arguments participants conform to rational
      Bayesian norms. It is suggested that logic and probability are not in competition
      and that the variety of norms is more limited than the arguments against
      evaluative normativity suppose. Moreover, the universality of belief ascription
      suggests that many of our norms are universal and hence evaluative. It is
      concluded that the union of evaluative normativity and descriptive psychology
      implicit in Davidson and apparent in the psychology of reasoning is a good thing.

PMID- 24860520
TI  - Hauntings, homeopathy, and the Hopkinsville Goblins: using pseudoscience to teach
      scientific thinking.
AB  - With access to information ever increasing, it is essential that students acquire
      the skills to distinguish fact from fiction. By incorporating examples of
      pseudoscience into lectures, instructors can provide students with the tools
      needed to understand the difference between scientific and pseudoscientific or
      paranormal claims. We discuss examples involving psychics, ghosts, aliens, and
      other phenomena in relation to scientific thinking. In light of research
      literature demonstrating that presenting and dispelling scientific misconceptions
      in the classroom is an effective means of countering non-scientific or
      pseudoscientific beliefs, we provide examples of pseudoscience that can be used
      to help students acquire healthy skepticism while avoiding cynicism. 

PMID- 24860521
TI  - A clinical case study of the use of ecological momentary assessment in obsessive
      compulsive disorder.
AB  - Accurate assessment of obsessions and compulsions is a crucial step in treatment
      planning for Obsessive-Compulsive Disorder (OCD). In this clinical case study, we
      sought to determine if the use of Ecological Momentary Assessment (EMA) could
      provide additional symptom information beyond that captured during standard
      assessment of OCD. We studied three adults diagnosed with OCD and compared the
      number and types of obsessions and compulsions captured using the Yale-Brown
      Obsessive-Compulsive Scale (Y-BOCS) compared to EMA. Following completion of the
      Y-BOCS interview, participants then recorded their OCD symptoms into a digital
      voice recorder across a 12-h period in reply to randomly sent mobile phone SMS
      prompts. The EMA approach yielded a lower number of symptoms of obsessions and
      compulsions than the Y-BOCS but produced additional types of obsessions and
      compulsions not previously identified by the Y-BOCS. We conclude that the EMA-OCD
      procedure may represent a worthy addition to the suite of assessment tools used
      when working with clients who have OCD. Further research with larger samples is
      required to strengthen this conclusion. 

PMID- 24860522
TI  - Do ambient urban odors evoke basic emotions?
AB  - Fragrances, such as plant odors, have been shown to evoke autonomic response
      patterns associated with Ekman's (Ekman et al., 1983) basic emotions happiness,
      surprise, anger, fear, sadness, and disgust. Inducing positive emotions by odors
      in highly frequented public spaces could serve to improve the quality of life in
      urban environments. Thus, the present study evaluated the potency of ambient
      odors connoted with an urban environment to evoke basic emotions on an autonomic
      and cognitive response level. Synthetic mixtures representing the odors of
      disinfectant, candles/bees wax, summer air, burnt smell, vomit and musty smell as
      well as odorless water as a control were presented five times in random order to
      30 healthy, non-smoking human subjects with intact sense of smell. Skin
      temperature, skin conductance, breathing rate, forearm muscle activity, blink
      rate, and heart rate were recorded simultaneously. Subjects rated the odors in
      terms of pleasantness, intensity and familiarity and gave verbal labels to each
      odor as well as cognitive associations with the basic emotions. The results
      showed that the amplitude of the skin conductance response (SCR) varied as a
      function of odor presentation. Burnt smell and vomit elicited significantly
      higher electrodermal responses than summer air. Also, a negative correlation was
      revealed between the amplitude of the SCR and hedonic odor valence indicating
      that the magnitude of the electrodermal response increased with odor
      unpleasantness. The analysis of the cognitive associations between odors and
      basic emotions showed that candles/bees wax and summer air were specifically
      associated with happiness whereas burnt smell and vomit were uniquely associated
      with disgust. Our findings suggest that city odors may evoke specific cognitive
      associations of basic emotions and that autonomic activity elicited by such odors
      is related to odor hedonics. 

PMID- 24860523
TI  - Order of the major constituents in sign languages: implications for all language.
AB  - A survey of reports of sign order from 42 sign languages leads to a handful of
      generalizations. Two accounts emerge, one amodal and the other modal. We argue
      that universal pressures are at work with respect to some generalizations, but
      that pressure from the visual modality is at work with respect to others.
      Together, these pressures conspire to make all sign languages order their major
      constituents SOV or SVO. This study leads us to the conclusion that the order of
      S with regard to verb phrase (VP) may be driven by sensorimotor system concerns
      that feed universal grammar. 

PMID- 24860524
TI  - When linguists talk mathematical logic.

PMID- 24860525
TI  - Using a high-dimensional graph of semantic space to model relationships among
      words.
AB  - The GOLD model (Graph Of Language Distribution) is a network model constructed
      based on co-occurrence in a large corpus of natural language that may be used to
      explore what information may be present in a graph-structured model of language,
      and what information may be extracted through theoretically-driven algorithms as
      well as standard graph analysis methods. The present study will employ GOLD to
      examine two types of relationship between words: semantic similarity and
      associative relatedness. Semantic similarity refers to the degree of overlap in
      meaning between words, while associative relatedness refers to the degree to
      which two words occur in the same schematic context. It is expected that a graph
      structured model of language constructed based on co-occurrence should easily
      capture associative relatedness, because this type of relationship is thought to
      be present directly in lexical co-occurrence. However, it is hypothesized that
      semantic similarity may be extracted from the intersection of the set of first
      order connections, because two words that are semantically similar may occupy
      similar thematic or syntactic roles across contexts and thus would co-occur
      lexically with the same set of nodes. Two versions the GOLD model that differed
      in terms of the co-occurence window, bigGOLD at the paragraph level and smallGOLD
      at the adjacent word level, were directly compared to the performance of a well
      established distributional model, Latent Semantic Analysis (LSA). The superior
      performance of the GOLD models (big and small) suggest that a single acquisition
      and storage mechanism, namely co-occurrence, can account for associative and
      conceptual relationships between words and is more psychologically plausible than
      models using singular value decomposition (SVD). 

PMID- 24860527
TI  - Concerns with the SDT approach to causal conditional reasoning: a comment on
      Trippas, Handley, Verde, Roser, McNair, and Evans (2014).

PMID- 24860526
TI  - Multisensory and modality specific processing of visual speech in different
      regions of the premotor cortex.
AB  - Behavioral and neuroimaging studies have demonstrated that brain regions involved
      with speech production also support speech perception, especially under degraded
      conditions. The premotor cortex (PMC) has been shown to be active during both
      observation and execution of action ("Mirror System" properties), and may
      facilitate speech perception by mapping unimodal and multimodal sensory features
      onto articulatory speech gestures. For this functional magnetic resonance imaging
      (fMRI) study, participants identified vowels produced by a speaker in audio
      visual (saw the speaker's articulating face and heard her voice), visual only
      (only saw the speaker's articulating face), and audio only (only heard the
      speaker's voice) conditions with varying audio signal-to-noise ratios in order to
      determine the regions of the PMC involved with multisensory and modality specific
      processing of visual speech gestures. The task was designed so that
      identification could be made with a high level of accuracy from visual only
      stimuli to control for task difficulty and differences in intelligibility. The
      results of the functional magnetic resonance imaging (fMRI) analysis for visual
      only and audio-visual conditions showed overlapping activity in inferior frontal
      gyrus and PMC. The left ventral inferior premotor cortex (PMvi) showed properties
      of multimodal (audio-visual) enhancement with a degraded auditory signal. The
      left inferior parietal lobule and right cerebellum also showed these properties.
      The left ventral superior and dorsal premotor cortex (PMvs/PMd) did not show this
      multisensory enhancement effect, but there was greater activity for the visual
      only over audio-visual conditions in these areas. The results suggest that the
      inferior regions of the ventral premotor cortex are involved with integrating
      multisensory information, whereas, more superior and dorsal regions of the PMC
      are involved with mapping unimodal (in this case visual) sensory features of the
      speech signal with articulatory speech gestures. 

PMID- 24860528
TI  - Test battery for measuring the perception and recognition of facial expressions
      of emotion.
AB  - Despite the importance of perceiving and recognizing facial expressions in
      everyday life, there is no comprehensive test battery for the multivariate
      assessment of these abilities. As a first step toward such a compilation, we
      present 16 tasks that measure the perception and recognition of facial emotion
      expressions, and data illustrating each task's difficulty and reliability. The
      scoring of these tasks focuses on either the speed or accuracy of performance. A
      sample of 269 healthy young adults completed all tasks. In general, accuracy and
      reaction time measures for emotion-general scores showed acceptable and high
      estimates of internal consistency and factor reliability. Emotion-specific scores
      yielded lower reliabilities, yet high enough to encourage further studies with
      such measures. Analyses of task difficulty revealed that all tasks are suitable
      for measuring emotion perception and emotion recognition related abilities in
      normal populations. 

PMID- 24860529
TI  - A new adaptive videogame for training attention and executive functions: design
      principles and initial validation.
AB  - A growing body of evidence suggests that action videogames could enhance a
      variety of cognitive skills and more specifically attention skills. The aim of
      this study was to develop a novel adaptive videogame to support the
      rehabilitation of the most common consequences of traumatic brain injury (TBI),
      that is the impairment of attention and executive functions. TBI patients can be
      affected by psychomotor slowness and by difficulties in dealing with distraction,
      maintain a cognitive set for a long time, processing different simultaneously
      presented stimuli, and planning purposeful behavior. Accordingly, we designed a
      videogame that was specifically conceived to activate those functions. Playing
      involves visuospatial planning and selective attention, active maintenance of the
      cognitive set representing the goal, and error monitoring. Moreover, different
      game trials require to alternate between two tasks (i.e., task switching) or to
      perform the two tasks simultaneously (i.e., divided attention/dual-tasking). The
      videogame is controlled by a multidimensional adaptive algorithm that calibrates
      task difficulty on-line based on a model of user performance that is updated on a
      trial-by-trial basis. We report simulations of user performance designed to test
      the adaptive game as well as a validation study with healthy participants engaged
      in a training protocol. The results confirmed the involvement of the cognitive
      abilities that the game is supposed to enhance and suggested that training
      improved attentional control during play. 

PMID- 24860531
TI  - Complex hand dexterity: a review of biomechanical methods for measuring musical
      performance.
AB  - Complex hand dexterity is fundamental to our interactions with the physical,
      social, and cultural environment. Dexterity can be an expression of creativity
      and precision in a range of activities, including musical performance. Little is
      understood about complex hand dexterity or how virtuoso expertise is acquired,
      due to the versatility of movement combinations available to complete any given
      task. This has historically limited progress of the field because of difficulties
      in measuring movements of the hand. Recent developments in methods of motion
      capture and analysis mean it is now possible to explore the intricate movements
      of the hand and fingers. These methods allow us insights into the
      neurophysiological mechanisms underpinning complex hand dexterity and motor
      learning. They also allow investigation into the key factors that contribute to
      injury, recovery and functional compensation. The application of such analytical
      techniques within musical performance provides a multidisciplinary framework for
      purposeful investigation into the process of learning and skill acquisition in
      instrumental performance. These highly skilled manual and cognitive tasks present
      the ultimate achievement in complex hand dexterity. This paper will review
      methods of assessing instrumental performance in music, focusing specifically on
      biomechanical measurement and the associated technical challenges faced when
      measuring highly dexterous activities. 

PMID- 24860530
TI  - Stochastic accumulation of feature information in perception and memory.
AB  - It is now well established that the time course of perceptual processing
      influences the first second or so of performance in a wide variety of cognitive
      tasks. Over the last 20 years, there has been a shift from modeling the speed at
      which a display is processed, to modeling the speed at which different features
      of the display are perceived and formalizing how this perceptual information is
      used in decision making. The first of these models (Lamberts, 1995) was
      implemented to fit the time course of performance in a speeded perceptual
      categorization task and assumed a simple stochastic accumulation of feature
      information. Subsequently, similar approaches have been used to model performance
      in a range of cognitive tasks including identification, absolute identification,
      perceptual matching, recognition, visual search, and word processing, again
      assuming a simple stochastic accumulation of feature information from both the
      stimulus and representations held in memory. These models are typically fit to
      data from signal-to-respond experiments whereby the effects of stimulus exposure
      duration on performance are examined, but response times (RTs) and RT
      distributions have also been modeled. In this article, we review this approach
      and explore the insights it has provided about the interplay between perceptual
      processing, memory retrieval, and decision making in a variety of tasks. In so
      doing, we highlight how such approaches can continue to usefully contribute to
      our understanding of cognition. 

PMID- 24860532
TI  - How number-space relationships are assessed before formal schooling: A taxonomy
      proposal.
AB  - The last years of research on numerical development have provided evidence that
      spatial-numerical associations (SNA) can be formed independent of formal school
      training. However, most of these studies used various experimental paradigms that
      referred to slightly different aspects of number and space processing. This poses
      a question of whether all SNAs described in the developmental literature can be
      interpreted as a unitary construct, or whether they are rather examples of
      different, but related phenomena. Our review aims to provide a starting point for
      a systematic classification of SNA measures used from infancy to late preschool
      years, and their underlying representations. We propose to distinguish among four
      basic SNA categories: (i) cross-dimensional magnitude processing, (ii)
      associations between spatial and numerical intervals, (iii) associations between
      cardinalities and spatial directions, (iv) associations between ordinalities and
      spatial directions. Such systematization allows for identifying similarities and
      differences between processes and representations that underlie the described
      measures, and also for assessing the adequacy of using different SNA tasks at
      different developmental stages. 

PMID- 24860533
TI  - The sound of your lips: electrophysiological cross-modal interactions during hand
      to-face and face-to-face speech perception.
AB  - Recent magneto-encephalographic and electro-encephalographic studies provide
      evidence for cross-modal integration during audio-visual and audio-haptic speech
      perception, with speech gestures viewed or felt from manual tactile contact with
      the speaker's face. Given the temporal precedence of the haptic and visual
      signals on the acoustic signal in these studies, the observed modulation of N1/P2
      auditory evoked responses during bimodal compared to unimodal speech perception
      suggest that relevant and predictive visual and haptic cues may facilitate
      auditory speech processing. To further investigate this hypothesis, auditory
      evoked potentials were here compared during auditory-only, audio-visual and audio
      haptic speech perception in live dyadic interactions between a listener and a
      speaker. In line with previous studies, auditory evoked potentials were
      attenuated and speeded up during both audio-haptic and audio-visual compared to
      auditory speech perception. Importantly, the observed latency and amplitude
      reduction did not significantly depend on the degree of visual and haptic
      recognition of the speech targets. Altogether, these results further demonstrate
      cross-modal interactions between the auditory, visual and haptic speech signals.
      Although they do not contradict the hypothesis that visual and haptic sensory
      inputs convey predictive information with respect to the incoming auditory speech
      input, these results suggest that, at least in live conversational interactions,
      systematic conclusions on sensory predictability in bimodal speech integration
      have to be taken with caution, with the extraction of predictive cues likely
      depending on the variability of the speech stimuli. 

PMID- 24860534
TI  - Helping the self help others: self-affirmation increases self-compassion and pro
      social behaviors.
AB  - Reflecting on an important personal value in a self-affirmation activity has been
      shown to improve psychological functioning in a broad range of studies, but the
      underlying mechanisms for these self-affirmation effects are unknown. Here we
      provide an initial test of a novel self-compassion account of self-affirmation in
      two experimental studies. Study 1 shows that an experimental manipulation of self
      affirmation (3-min of writing about an important personal value vs. writing about
      an unimportant value) increases feelings of self-compassion, and these feelings
      in turn mobilize more pro-social behaviors to a laboratory shelf-collapse
      incident. Study 2 tests and extends these effects by evaluating whether self
      affirmation increases feelings of compassion toward the self (consistent with the
      self-compassion account) or increases feelings of compassion toward others (an
      alternative other-directed compassion account), using a validated storytelling
      behavioral task. Consistent with a self-compassion account, Study 2 demonstrates
      the predicted self-affirmation by video condition interaction, indicating that
      self-affirmation participants had greater feelings of self-compassion in response
      to watching their own storytelling performance (self-compassion) compared to
      watching a peer's storytelling performance (other-directed compassion). Further,
      pre-existing levels of trait self-compassion moderated this effect, such that
      self-affirmation increased self-compassionate responses the most in participants
      low in trait self-compassion. This work suggests that self-compassion may be a
      promising mechanism for self-affirmation effects, and that self-compassionate
      feelings can mobilize pro-social behaviors. 

PMID- 24860535
TI  - Adult age-differences in subjective impression of emotional faces are reflected
      in emotion-related attention and memory tasks.
AB  - Although younger and older adults appear to attend to and remember emotional
      faces differently, less is known about age-related differences in the subjective
      emotional impression (arousal, potency, and valence) of emotional faces and how
      these differences, in turn, are reflected in age differences in various emotional
      tasks. In the current study, we used the same facial emotional stimuli (angry and
      happy faces) in four tasks: emotional rating, attention, categorical perception,
      and visual short-term memory (VSTM). The aim of this study was to investigate
      effects of age on the subjective emotional impression of angry and happy faces
      and to examine whether any age differences were mirrored in measures of emotional
      behavior (attention, categorical perception, and memory). In addition, regression
      analyses were used to further study impression-behavior associations. Forty
      younger adults (range 20-30 years) and thirty-nine older adults (range 65-75
      years) participated in the experiment. The emotional rating task showed that
      older adults perceived less arousal, potency, and valence than younger adults and
      that the difference was more pronounced for angry than happy faces. Similarly,
      the results of the attention and memory tasks demonstrated interaction effects
      between emotion and age, and age differences on these measures were larger for
      angry than for happy faces. Regression analyses confirmed that in both age
      groups, higher potency ratings predicted both visual search and VSTM efficiency.
      Future studies should consider the possibility that age differences in the
      subjective emotional impression of facial emotional stimuli may explain age
      differences in attention to and memory of such stimuli. 

PMID- 24860536
TI  - Discriminating languages in bilingual contexts: the impact of orthographic
      markedness.
AB  - Does language-specific orthography help language detection and lexical access in
      naturalistic bilingual contexts? This study investigates how L2 orthotactic
      properties influence bilingual language detection in bilingual societies and the
      extent to which it modulates lexical access and single word processing. Language
      specificity of naturalistically learnt L2 words was manipulated by including
      bigram combinations that could be either L2 language-specific or common in the
      two languages known by bilinguals. A group of balanced bilinguals and a group of
      highly proficient but unbalanced bilinguals who grew up in a bilingual society
      were tested, together with a group of monolinguals (for control purposes). All
      the participants completed a speeded language detection task and a progressive
      demasking task. Results showed that the use of the information of orthotactic
      rules across languages depends on the task demands at hand, and on participants'
      proficiency in the second language. The influence of language orthotactic rules
      during language detection, lexical access and word identification are discussed
      according to the most prominent models of bilingual word recognition. 

PMID- 24860537
TI  - The influence of empathic concern on prosocial behavior in children.
AB  - This research explored the influence of empathic distress on prosocial behavior
      in a resource allocation task with children. Children were randomly assigned to
      one of two conditions before engaging in a sticker sharing task; watching either
      a video of a girl upset that her dog had gone missing (emotion induction
      condition), or a video of the same girl preparing for a yard sale (control
      condition). In study one, 5-6 year old children in the emotion induction
      condition rated the emotional state of both the protagonist and the self more
      negatively, and also exhibited more prosocial behavior; sharing more in
      advantageous inequity (AI) trials, and less often withholding a benefit in
      disadvantageous inequity trials, than the control group. Prosocial behavior was
      significantly correlated with ratings of the emotional state of the protagonist
      but not with own emotional state, suggesting that empathic concern rather than
      personal distress was the primary influence on prosocial behavior. In study two,
      3-year-olds were tested on AI trials alone, and like the 5 and 6-year-olds,
      showed more prosocial behavior in the emotion induction condition than the
      control. 

PMID- 24860538
TI  - Motion processing: the most sensitive detectors differ in temporally localized
      and extended noise.
AB  - Contrast thresholds for discriminating orientation and direction of a drifting,
      oriented grating are usually similar to contrast detection thresholds, which
      suggest that the most sensitive detectors are labeled for both orientation and
      direction (Watson and Robson, 1981). This was found to be true in noiseless
      condition, but Arena et al. (2013) recently found that this was not true in
      localized noise (i.e., noise having the same spatiotemporal window as the target)
      as thresholds for discriminating direction were higher than for discriminating
      orientation. They suggested that this could be explained by the fact that there
      are more neurons selective to orientation than direction. Another possible
      interpretation is that, unlike contrast thresholds in absence of noise, the most
      sensitive detectors in localized noise were labeled for orientation, but not for
      direction. This hypothesis is supported by recent findings showing different
      processes operating in localized and extended noise (i.e., full-screen,
      continuously displayed noise, Allard and Cavanagh, 2011). In the current study,
      we evaluated contrast thresholds for orientation and direction discrimination
      tasks in noiseless conditions, and in noise that was either spatially localized
      or extended, and temporally localized or extended. We found similar orientation
      and direction thresholds in absence of noise and in temporally extended noise,
      but greater direction thresholds in temporally localized noise. This suggests
      that in noiseless and temporally extended noise the most sensitive detectors were
      labeled for both orientation and direction (e.g., direction-selective complex
      cells), whereas in temporally localized noise the most sensitive detectors were
      labeled for orientation but not direction (e.g., simple cells). We conclude that
      to avoid violating the noise-invariant processing assumption, external noise
      paradigms investigating motion processing should use noise that is temporally
      extended, not localized. 

PMID- 24860539
TI  - Lexical access in sign language: a computational model.
AB  - PSYCHOLINGUISTIC THEORIES HAVE PREDOMINANTLY BEEN BUILT UPON DATA FROM SPOKEN
      LANGUAGE, WHICH LEAVES OPEN THE QUESTION: How many of the conclusions truly
      reflect language-general principles as opposed to modality-specific ones? We take
      a step toward answering this question in the domain of lexical access in
      recognition by asking whether a single cognitive architecture might explain
      diverse behavioral patterns in signed and spoken language. Chen and Mirman (2012)
      presented a computational model of word processing that unified opposite effects
      of neighborhood density in speech production, perception, and written word
      recognition. Neighborhood density effects in sign language also vary depending on
      whether the neighbors share the same handshape or location. We present a
      spreading activation architecture that borrows the principles proposed by Chen
      and Mirman (2012), and show that if this architecture is elaborated to
      incorporate relatively minor facts about either (1) the time course of sign
      perception or (2) the frequency of sub-lexical units in sign languages, it
      produces data that match the experimental findings from sign languages. This work
      serves as a proof of concept that a single cognitive architecture could underlie
      both sign and word recognition. 

PMID- 24860540
TI  - "Does he need help or can he help himself?" Preschool children's expectations
      about others' instrumental helping versus self-helping.
AB  - In the present study, we investigated a total of fifty-one 3.5-, 4.5-, and 5.5
      year-old children's expectations about another person's helping behaviors. We
      asked children to complete a story in which one person failed to complete his
      goal (e.g., because an object was misplaced or put out of his reach) while the
      other person observed the event. We asked whether the children expected the other
      person to help the protagonist or whether they expected the protagonist to help
      himself. Children of 3.5 years expected the other person to provide help in the
      majority of trials. In contrast, the older children were equally likely to
      predict that the other person would help the protagonist or the protagonist would
      help himself. 

PMID- 24860542
TI  - The nature of thinking, shallow and deep.
AB  - Because the criteria for success differ across various domains of life, no single
      normative standard will ever work for all types of thinking. One method for
      dealing with this apparent dilemma is to propose that the mind is made up of a
      large number of specialized modules. This review describes how this multi-modular
      framework for the mind overcomes several critical conceptual and theoretical
      challenges to our understanding of human thinking, and hopefully clarifies what
      are (and are not) some of the implications based on this framework. In
      particular, an evolutionarily informed "deep rationality" conception of human
      thinking can guide psychological research out of clusters of ad hoc models which
      currently occupy some fields. First, the idea of deep rationality helps
      theoretical frameworks in terms of orienting themselves with regard to time scale
      references, which can alter the nature of rationality assessments. Second, the
      functional domains of deep rationality can be hypothesized (non-exhaustively) to
      include the areas of self-protection, status, affiliation, mate acquisition, mate
      retention, kin care, and disease avoidance. Thus, although there is no single
      normative standard of rationality across all of human cognition, there are
      sensible and objective standards by which we can evaluate multiple, fundamental,
      domain-specific motives underlying human cognition and behavior. This review
      concludes with two examples to illustrate the implications of this framework. The
      first example, decisions about having a child, illustrates how competing models
      can be understood by realizing that different fundamental motives guiding
      people's thinking can sometimes be in conflict. The second example is that of
      personifications within modern financial markets (e.g., in the form of
      corporations), which are entities specifically constructed to have just one
      fundamental motive. This single focus is the source of both the strengths and
      flaws in how such entities behave. 

PMID- 24860541
TI  - Eating behavior and stress: a pathway to obesity.
AB  - Stress causes or contributes to a huge variety of diseases and disorders. Recent
      evidence suggests obesity and other eating-related disorders may be among these.
      Immediately after a stressful event is experienced, there is a corticotropin
      releasing-hormone (CRH)-mediated suppression of food intake. This diverts the
      body's resources away from the less pressing need to find and consume food,
      prioritizing fight, flight, or withdrawal behaviors so the stressful event can be
      dealt with. In the hours following this, however, there is a glucocorticoid
      mediated stimulation of hunger and eating behavior. In the case of an acute
      stress that requires a physical response, such as a predator-prey interaction,
      this hypothalamic-pituitary-adrenal (HPA) axis modulation of food intake allows
      the stressful event to be dealt with and the energy used to be replaced
      afterward. In the case of ongoing psychological stress, however, chronically
      elevated glucocorticoids can lead to chronically stimulated eating behavior and
      excessive weight gain. In particular, stress can enhance the propensity to eat
      high calorie "palatable" food via its interaction with central reward pathways.
      Activation of this circuitry can also interact with the HPA axis to suppress its
      further activation, meaning not only can stress encourage eating behavior, but
      eating can suppress the HPA axis and the feeling of stress. In this review we
      will explore the theme of eating behavior and stress and how these can modulate
      one another. We will address the interactions between the HPA axis and eating,
      introducing a potential integrative role for the orexigenic hormone, ghrelin. We
      will also examine early life and epigenetic modulation of the HPA axis and how
      this can influence eating behavior. Finally, we will investigate the clinical
      implications of changes to HPA axis function and how this may be contributing to
      obesity in our society. 

PMID- 24860543
TI  - The effects of distraction on metacognition and metacognition on distraction:
      evidence from recognition memory.
AB  - The effects of auditory distraction in memory tasks have, to date, been examined
      with procedures that minimize participants' control over their own memory
      processes. Surprisingly little attention has been paid to metacognitive control
      factors which might affect memory performance. In this study, we investigate the
      effects of auditory distraction on metacognitive control of memory, examining the
      effects of auditory distraction in recognition tasks utilizing the metacognitive
      framework of Koriat and Goldsmith (1996), to determine whether strategic
      regulation of memory accuracy is impacted by auditory distraction. Results
      replicated previous findings in showing that auditory distraction impairs memory
      performance in tasks minimizing participants' metacognitive control (forced
      report test). However, the results revealed also that when metacognitive control
      is allowed (free-report tests), auditory distraction impacts upon a range of
      metacognitive indices. In the present study, auditory distraction undermined
      accuracy of metacognitive monitoring (resolution), reduced confidence in
      responses provided and, correspondingly, increased participants' propensity to
      withhold responses in free-report recognition. Crucially, changes in
      metacognitive processes were related to impairment in free-report recognition
      performance, as the use of the "don't know" option under distraction led to a
      reduction in the number of correct responses volunteered in free-report tests.
      Overall, the present results show how auditory distraction exerts its influence
      on memory performance via both memory and metamemory processes. 

PMID- 24860544
TI  - The worldly constituents of perceptual presence.

PMID- 24860545
TI  - Three-Class Differential Diagnosis among Alzheimer Disease, Frontotemporal
      Dementia, and Controls.
AB  - Biomarkers derived from brain magnetic resonance (MR) imaging have promise in
      being able to assist in the clinical diagnosis of brain pathologies. These have
      been used in many studies in which the goal has been to distinguish between
      pathologies such as Alzheimer's disease and healthy aging. However, other
      dementias, in particular, frontotemporal dementia, also present overlapping
      pathological brain morphometry patterns. Hence, a classifier that can
      discriminate morphometric features from a brain MRI from the three classes of
      normal aging, Alzheimer's disease (AD), and frontotemporal dementia (FTD) would
      offer considerable utility in aiding in correct group identification. Compared to
      the conventional use of multiple pair-wise binary classifiers that learn to
      discriminate between two classes at each stage, we propose a single three-way
      classification system that can discriminate between three classes at the same
      time. We present a novel classifier that is able to perform a three-class
      discrimination test for discriminating among AD, FTD, and normal controls (NC)
      using volumes, shape invariants, and local displacements (three features) of
      hippocampi and lateral ventricles (two structures times two hemispheres
      individually) obtained from brain MR images. In order to quantify its utility in
      correct discrimination, we optimize the three-class classifier on a training set
      and evaluate its performance using a separate test set. This is a novel, first-of
      its-kind comparative study of multiple individual biomarkers in a three-class
      setting. Our results demonstrate that local atrophy features in lateral
      ventricles offer the potential to be a biomarker in discriminating among AD, FTD,
      and NC in a three-class setting for individual patient classification. 

PMID- 24860546
TI  - Coherent Activity in Bilateral Parieto-Occipital Cortices during P300-BCI
      Operation.
AB  - The visual P300 brain-computer interface (BCI), a popular system for
      electroencephalography (EEG)-based BCI, uses the P300 event-related potential to
      select an icon arranged in a flicker matrix. In earlier studies, we used
      green/blue (GB) luminance and chromatic changes in the P300-BCI system and
      reported that this luminance and chromatic flicker matrix was associated with
      better performance and greater subject comfort compared with the conventional
      white/gray (WG) luminance flicker matrix. To highlight areas involved in improved
      P300-BCI performance, we used simultaneous EEG-fMRI recordings and showed
      enhanced activities in bilateral and right lateralized parieto-occipital areas.
      Here, to capture coherent activities of the areas during P300-BCI, we collected
      whole-head 306-channel magnetoencephalography data. When comparing functional
      connectivity between the right and left parieto-occipital channels, significantly
      greater functional connectivity in the alpha band was observed under the GB
      flicker matrix condition than under the WG flicker matrix condition. Current
      sources were estimated with a narrow-band adaptive spatial filter, and mean
      imaginary coherence was computed in the alpha band. Significantly greater
      coherence was observed in the right posterior parietal cortex under the GB than
      under the WG condition. Re-analysis of previous EEG-based P300-BCI data showed
      significant correlations between the power of the coherence of the bilateral
      parieto-occipital cortices and their performance accuracy. These results suggest
      that coherent activity in the bilateral parieto-occipital cortices plays a
      significant role in effectively driving the P300-BCI. 

PMID- 24860547
TI  - Biased signaling of protease-activated receptors.
AB  - In addition to their role in protein degradation and digestion, proteases can
      also function as hormone-like signaling molecules that regulate vital patho
      physiological processes, including inflammation, hemostasis, pain, and repair
      mechanisms. Certain proteases can signal to cells by cleaving protease-activated
      receptors (PARs), a family of four G protein-coupled receptors. PARs are
      expressed by almost all cell types, control important physiological and disease
      relevant processes, and are an emerging therapeutic target for major diseases.
      Most information about PAR activation and function derives from studies of a few
      proteases, for example thrombin in the case of PAR1, PAR3, and PAR4, and trypsin
      in the case of PAR2 and PAR4. These proteases cleave PARs at established sites
      with the extracellular N-terminal domains, and expose tethered ligands that
      stabilize conformations of the cleaved receptors that activate the canonical
      pathways of G protein- and/or beta-arrestin-dependent signaling. However, a
      growing number of proteases have been identified that cleave PARs at divergent
      sites to activate distinct patterns of receptor signaling and trafficking. The
      capacity of these proteases to trigger distinct signaling pathways is referred to
      as biased signaling, and can lead to unique patho-physiological outcomes. Given
      that a different repertoire of proteases are activated in various patho
      physiological conditions that may activate PARs by different mechanisms,
      signaling bias may account for the divergent actions of proteases and PARs.
      Moreover, therapies that target disease-relevant biased signaling pathways may be
      more effective and selective approaches for the treatment of protease- and PAR
      driven diseases. Thus, rather than mediating the actions of a few proteases, PARs
      may integrate the biological actions of a wide spectrum of proteases in different
      patho-physiological conditions. 

PMID- 24860549
TI  - Venus kinase receptors: prospects in signaling and biological functions of these
      invertebrate kinases.
AB  - Venus kinase receptors (VKRs) form a family of invertebrate receptor tyrosine
      kinases (RTKs) initially discovered in the parasitic platyhelminth Schistosoma
      mansoni. VKRs are single transmembrane receptors that contain an extracellular
      venus fly trap structure similar to the ligand-binding domain of G protein
      coupled receptors of class C, and an intracellular tyrosine kinase domain close
      to that of insulin receptors. VKRs are found in a large variety of invertebrates
      from cnidarians to echinoderms and are highly expressed in larval stages and in
      gonads, suggesting a role of these proteins in embryonic and larval development
      as well as in reproduction. VKR gene silencing could demonstrate the function of
      these receptors in oogenesis as well as in spermatogenesis in S. mansoni. VKRs
      are activated by amino acids and are highly responsive to arginine. As many other
      RTKs, they form dimers when activated by ligands and induce intracellular
      pathways involved in protein synthesis and cellular growth, such as MAPK and
      PI3K/Akt/S6K pathways. VKRs are not present in vertebrates or in some
      invertebrate species. Questions remain open about the origin of this little-known
      RTK family in evolution and its role in emergence and specialization of Metazoa.
      What is the meaning of maintenance or loss of VKR in some phyla or species in
      terms of development and physiological functions? The presence of VKRs in
      invertebrates of economical and medical importance, such as pests, vectors of
      pathogens, and platyhelminth parasites, and the implication of these RTKs in
      gametogenesis and reproduction processes are valuable reasons to consider VKRs as
      interesting targets in new programs for eradication/control of pests and
      infectious diseases, with the main advantage in the case of parasite targeting
      that VKR counterparts are absent from the vertebrate host kinase panel. 

PMID- 24860548
TI  - Diversity and Bias through Receptor-Receptor Interactions in GPCR Heteroreceptor
      Complexes. Focus on Examples from Dopamine D2 Receptor Heteromerization.
AB  - Allosteric receptor-receptor interactions in GPCR heteromers appeared to
      introduce an intermolecular allosteric mechanism contributing to the diversity
      and bias in the protomers. Examples of dopamine D2R heteromerization are given to
      show how such allosteric mechanisms significantly change the receptor protomer
      repertoire leading to diversity and biased recognition and signaling. In 1980s
      and 1990s, it was shown that neurotensin (NT) through selective antagonistic NTR
      D2 like receptor interactions increased the diversity of DA signaling by reducing
      D2R-mediated dopamine signaling over D1R-mediated dopamine signaling.
      Furthermore, D2R protomer appeared to bias the specificity of the NTR orthosteric
      binding site toward neuromedin N vs. NT in the heteroreceptor complex. Complex
      CCK2R-D1R-D2R interactions in possible heteroreceptor complexes were also
      demonstrated further increasing receptor diversity. In D2R-5-HT2AR heteroreceptor
      complexes, the hallucinogenic 5-HT2AR agonists LSD and DOI were recently found to
      exert a biased agonist action on the orthosteric site of the 5-HT2AR protomer
      leading to the development of an active conformational state different from the
      one produced by 5-HT. Furthermore, as recently demonstrated allosteric A2A-D2R
      receptor-receptor interaction brought about not only a reduced affinity of the
      D2R agonist binding site but also a biased modulation of the D2R protomer
      signaling in A2A-D2R heteroreceptor complexes. A conformational state of the D2R
      was induced, which moved away from Gi/o signaling and instead favored beta
      arrestin2-mediated signaling. These examples on allosteric receptor-receptor
      interactions obtained over several decades serve to illustrate the significant
      increase in diversity and biased recognition and signaling that develop through
      such mechanisms. 

PMID- 24860550
TI  - Early-Life Stress, HPA Axis Adaptation, and Mechanisms Contributing to Later
      Health Outcomes.
AB  - Stress activates the hypothalamic-pituitary-adrenal (HPA) axis, which then
      modulates the degree of adaptation and response to a later stressor. It is known
      that early-life stress can impact on later health but less is known about how
      early-life stress impairs HPA axis activity, contributing to maladaptation of the
      stress-response system. Early-life stress exposure (either prenatally or in the
      early postnatal period) can impact developmental pathways resulting in lasting
      structural and regulatory changes that predispose to adulthood disease.
      Epidemiological, clinical, and experimental studies have demonstrated that early
      life stress produces long term hyper-responsiveness to stress with exaggerated
      circulating glucocorticoids, and enhanced anxiety and depression-like behaviors.
      Recently, evidence has emerged on early-life stress-induced metabolic
      derangements, for example hyperinsulinemia and altered insulin sensitivity on
      exposure to a high energy diet later in life. This draws our attention to the
      contribution of later environment to disease vulnerability. Early-life stress can
      alter the expression of genes in peripheral tissues, such as the glucocorticoid
      receptor and 11-beta hydroxysteroid dehydrogenase (11beta-HSD1). We propose that
      interactions between altered HPA axis activity and liver 11beta-HSD1 modulates
      both tissue and circulating glucocorticoid availability, with adverse metabolic
      consequences. This review discusses the potential mechanisms underlying early
      life stress-induced maladaptation of the HPA axis, and its subsequent effects on
      energy utilization and expenditure. The effects of positive later environments as
      a means of ameliorating early-life stress-induced health deficits, and proposed
      mechanisms underpinning the interaction between early-life stress and subsequent
      detrimental environmental exposures on metabolic risk will be outlined.
      Limitations in current methodology linking early-life stress and later health
      outcomes will also be addressed. 

PMID- 24860552
TI  - Metagenomic analysis of the medicinal leech gut microbiota.
AB  - There are trillions of microbes found throughout the human body and they exceed
      the number of eukaryotic cells by 10-fold. Metagenomic studies have revealed that
      the majority of these microbes are found within the gut, playing an important
      role in the host's digestion and nutrition. The complexity of the animal
      digestive tract, unculturable microbes, and the lack of genetic tools for most
      culturable microbes make it challenging to explore the nature of these microbial
      interactions within this niche. The medicinal leech, Hirudo verbana, has been
      shown to be a useful tool in overcoming these challenges, due to the simplicity
      of the microbiome and the availability of genetic tools for one of the two
      dominant gut symbionts, Aeromonas veronii. In this study, we utilize 16S rRNA
      gene pyrosequencing to further explore the microbial composition of the leech
      digestive tract, confirming the dominance of two taxa, the Rikenella-like
      bacterium and A. veronii. The deep sequencing approach revealed the presence of
      additional members of the microbial community that suggests the presence of a
      moderately complex microbial community with a richness of 36 taxa. The presence
      of a Proteus strain as a newly identified resident in the leech crop was
      confirmed using fluorescence in situ hybridization (FISH). The metagenome of this
      community was also pyrosequenced and the contigs were binned into the following
      taxonomic groups: Rikenella-like (3.1 MB), Aeromonas (4.5 MB), Proteus (2.9 MB),
      Clostridium (1.8 MB), Eryspelothrix (0.96 MB), Desulfovibrio (0.14 MB), and
      Fusobacterium (0.27 MB). Functional analyses on the leech gut symbionts were
      explored using the metagenomic data and MG-RAST. A comparison of the COG and KEGG
      categories of the leech gut metagenome to that of other animal digestive-tract
      microbiomes revealed that the leech digestive tract had a similar metabolic
      potential to the human digestive tract, supporting the usefulness of this system
      as a model for studying digestive-tract microbiomes. This study lays the
      foundation for more detailed metatranscriptomic studies and the investigation of
      symbiont population dynamics. 

PMID- 24860553
TI  - Various pAQU plasmids possibly contribute to disseminate tetracycline resistance
      gene tet(M) among marine bacterial community.
AB  - Emergence of antibiotic-resistant bacteria in the aquaculture environment is a
      significant problem for disease control of cultured fish as well as in human
      public health. Conjugative mobile genetic elements (MGEs) are involved in
      dissemination of antibiotic resistance genes (ARGs) among marine bacteria. In the
      present study, we first designed a PCR targeting traI gene encoding essential
      relaxase for conjugation. By this new PCR, we demonstrated that five of 83
      strains isolated from a coastal aquaculture site had traI-positive MGEs. While
      one of the five strains that belonged to Shewanella sp. was shown to have an
      integrative conjugative element of the SXT/R391 family (ICEVchMex-like), the MGEs
      of the other four strains of Vibrio spp. were shown to have the backbone
      structure similar to that of previously described in pAQU1. The backbone
      structure shared by the pAQU1-like plasmids in the four strains corresponded to a
      ~100-kbp highly conserved region required for replication, partition and
      conjugative transfer, suggesting that these plasmids constituted "pAQU group."
      The pAQU group plasmids were shown to be capable of conjugative transfer of
      tet(M) and other ARGs from the Vibrio strains to E. coli. The pAQU group plasmid
      in one of the examined strains was designated as pAQU2, and its complete
      nucleotide sequence was determined and compared with that of pAQU1. The results
      revealed that pAQU2 contained fewer ARGs than pAQU1 did, and most of the ARGs in
      both of these plasmids were located in the similar region where multiple
      transposases were found, suggesting that the ARGs were introduced by several
      events of DNA transposition into an ancestral plasmid followed by drug selection
      in the aquaculture site. The results of the present study indicate that the "pAQU
      group" plasmids may play an important role in dissemination of ARGs in the marine
      environment. 

PMID- 24860554
TI  - Osmoregulation and the human mycobiome.

PMID- 24860551
TI  - Neuropsychiatric comorbidity in obesity: role of inflammatory processes.
AB  - Neuropsychiatric symptoms are frequent in obesity. In addition to their
      substantial economic and health impact, these symptoms significantly interfere
      with the quality of life and social function of obese individuals. While the
      pathophysiological mechanisms underlying obesity-related neuropsychiatric
      symptoms are still under investigation and remain to be clearly identified, there
      is increasing evidence for a role of inflammatory processes. Obesity is
      characterized by a chronic low-grade inflammatory state that is likely to
      influence neuropsychiatric status given the well-known and highly documented
      effects of inflammation on brain activity/function and behavior. This hypothesis
      is supported by recent findings emanating from clinical investigations in obese
      subjects and from experimentations conducted in animal models of obesity. These
      studies converge to show that obesity-related inflammatory processes, originating
      either from the adipose tissue or gut microbiota environment, spread to the brain
      where they lead to substantial changes in neurocircuitry, neuroendocrine
      activity, neurotransmitter metabolism and activity, and neurogenesis. Together,
      these alterations contribute to shape the propitious bases for the development of
      obesity-related neuropsychiatric comorbidities. 

PMID- 24860556
TI  - Effect of methylglyoxal on multidrug-resistant Pseudomonas aeruginosa.
AB  - Honey has a complex chemistry, and its broad-spectrum antimicrobial activity
      varies with floral source, climate, and harvesting conditions. Methylglyoxal was
      identified as the dominant antibacterial component of manuka honey. Although it
      has been known that methylglyoxal has antibacterial activity against gram
      positive bacteria, including methicillin-resistant Staphylococcus aureus and
      vancomycin-resistant Enterococcus, there is not much information describing its
      activity against gram-negative bacteria. In this study, we report the effect of
      methylglyoxal against multidrug-resistant Pseudomonas aeruginosa (MDRP) using 53
      clinically isolated strains. We also assessed the effect of deleting the five
      multidrug efflux systems in P. aeruginosa, as well as the efflux systems in
      Escherichia coli and Salmonella enterica serovar Typhimurium, on MICs of
      methylglyoxal. Our results indicate that methylglyoxal inhibits the growth of
      MDRP at concentrations of 128-512 MUg/ml (1.7-7.1 mM) and is not recognized by
      drug efflux systems. 

PMID- 24860557
TI  - Adaptation to high salt concentrations in halotolerant/halophilic fungi: a
      molecular perspective.
AB  - Molecular studies of salt tolerance of eukaryotic microorganisms have until
      recently been limited to the baker's yeast Saccharomyces cerevisiae and a few
      other moderately halotolerant yeast. Discovery of the extremely halotolerant and
      adaptable fungus Hortaea werneckii and the obligate halophile Wallemia
      ichthyophaga introduced two new model organisms into studies on the mechanisms of
      salt tolerance in eukaryotes. H. werneckii is unique in its adaptability to
      fluctuations in salt concentrations, as it can grow without NaCl as well as in
      the presence of up to 5 M NaCl. On the other hand, W. ichthyophaga requires at
      least 1.5 M NaCl for growth, but also grows in up to 5 M NaCl. Our studies have
      revealed the novel and intricate molecular mechanisms used by these fungi to
      combat high salt concentrations, which differ in many aspects between the
      extremely halotolerant H. werneckii and the halophilic W. ichthyophaga.
      Specifically, the high osmolarity glycerol signaling pathway that is important
      for sensing and responding to increased salt concentrations is here compared
      between H. werneckii and W. ichthyophaga. In both of these fungi, the key
      signaling components are conserved, but there are structural and regulation
      differences between these pathways in H. werneckii and W. ichthyophaga. We also
      address differences that have been revealed from analysis of their newly
      sequenced genomes. The most striking characteristics associated with H. werneckii
      are the large genetic redundancy, the expansion of genes encoding metal cation
      transporters, and a relatively recent whole genome duplication. In contrast, the
      genome of W. ichthyophaga is very compact, as only 4884 protein-coding genes are
      predicted, which cover almost three quarters of the sequence. Importantly, there
      has been a significant increase in their hydrophobins, cell-wall proteins that
      have multiple cellular functions. 

PMID- 24860558
TI  - Wheat germ cell-free system-based production of hemagglutinin-neuraminidase
      glycoprotein of human parainfluenza virus type 3 for generation and
      characterization of monoclonal antibody.
AB  - Human parainfluenza virus 3 (HPIV3) commonly causes respiratory disorders in
      infants and young children. Monoclonal antibodies (MAbs) have been produced to
      several components of HPIV3 and commercially available. However, the utility of
      these antibodies for several immunological and proteomic assays for understanding
      the nature of HPIV3 infection remain to be characterized. Herein, we report the
      development and characterization of MAbs against hemagglutinin-neuraminidase (HN)
      of HPIV3. A recombinant full-length HPIV3-HN was successfully synthesized using
      the wheat-germ cell-free protein production system. After immunization and cell
      fusion, 36 mouse hybridomas producing MAbs to HPIV3-HN were established. The MAbs
      obtained were fully characterized using ELISA, immunoblotting, and
      immunofluorescent analyses. Of the MAbs tested, single clone was found to be
      applicable in both flow cytometry and immunoprecipitation procedures. By
      utilizing the antibody, we identified HPIV3-HN binding host proteins via
      immunoprecipitation-based mass spectrometry analysis. The newly-developed MAbs
      could thus be a valuable tool for the study of HPIV3 infection as well as the
      several diagnostic tests of this virus. 

PMID- 24860559
TI  - Changes in the deep subsurface microbial biosphere resulting from a field-scale
      CO2 geosequestration experiment.
AB  - Subsurface microorganisms may respond to increased CO2 levels in ways that
      significantly affect pore fluid chemistry. Changes in CO2 concentration or
      speciation may result from the injection of supercritical CO2 (scCO2) into deep
      aquifers. Therefore, understanding subsurface microbial responses to scCO2, or
      unnaturally high levels of dissolved CO2, will help to evaluate the use of
      geosequestration to reduce atmospheric CO2 emissions. This study characterized
      microbial community changes at the 16S rRNA gene level during a scCO2
      geosequestration experiment in the 1.4 km-deep Paaratte Formation of the Otway
      Basin, Australia. One hundred and fifty tons of mixed scCO2 and groundwater was
      pumped into the sandstone Paaratte aquifer over 4 days. A novel U-tube sampling
      system was used to obtain groundwater samples under in situ pressure conditions
      for geochemical analyses and DNA extraction. Decreases in pH and temperature of
      2.6 log units and 5.8 degrees C, respectively, were observed. Polyethylene
      glycols (PEGs) were detected in the groundwater prior to scCO2 injection and were
      interpreted as residual from drilling fluid used during the emplacement of the
      CO2 injection well. Changes in microbial community structure prior to scCO2
      injection revealed a general shift from Firmicutes to Proteobacteria concurrent
      with the disappearance of PEGs. However, the scCO2 injection event, including
      changes in response to the associated variables (e.g., pH, temperature and
      salinity), resulted in increases in the relative abundances of Comamonadaceae and
      Sphingomonadaceae suggesting the potential for enhanced scCO2 tolerance of these
      groups. This study demonstrates a successful new in situ sampling approach for
      detecting microbial community changes associated with an scCO2 geosequestration
      event. 

PMID- 24860560
TI  - Evaluation of the biodegradation of Alaska North Slope oil in microcosms using
      the biodegradation model BIOB.
AB  - We present the details of a numerical model, BIOB that is capable of simulating
      the biodegradation of oil entrapped in the sediment. The model uses Monod
      kinetics to simulate the growth of bacteria in the presence of nutrients and the
      subsequent consumption of hydrocarbons. The model was used to simulate
      experimental results of Exxon Valdez oil biodegradation in laboratory columns
      (Venosa et al., 2010). In that study, samples were collected from three different
      islands: Eleanor Island (EL107), Knight Island (KN114A), and Smith Island
      (SM006B), and placed in laboratory microcosms for a duration of 168 days to
      investigate oil bioremediation through natural attenuation and nutrient
      amendment. The kinetic parameters of the BIOB model were estimated by fitting to
      the experimental data using a parameter estimation tool based on Genetic
      Algorithms (GA). The parameter values of EL107 and KN114A were similar whereas
      those of SM006B were different from the two other sites; in particular biomass
      growth at SM006B was four times slower than at the other two islands. Grain size
      analysis from each site revealed that the specific surface area per unit mass of
      sediment was considerably lower at SM006B, which suggest that the surface area of
      sediments is a key control parameter for microbial growth in sediments.
      Comparison of the BIOB results with exponential decay curves fitted to the data
      indicated that BIOB provided better fit for KN114A and SM006B in nutrient amended
      treatments, and for EL107 and KN114A in natural attenuation. In particular, BIOB
      was able to capture the initial slow biodegradation due to the lag phase in
      microbial growth. Sensitivity analyses revealed that oil biodegradation at all
      three locations were sensitive to nutrient concentration whereas SM006B was
      sensitive to initial biomass concentration due to its slow growth rate. Analyses
      were also performed to compare the half-lives of individual compounds with that
      of the overall polycyclic aromatic hydrocarbons (PAHs). 

PMID- 24860555
TI  - Recombinant protein expression in Escherichia coli: advances and challenges.
AB  - Escherichia coli is one of the organisms of choice for the production of
      recombinant proteins. Its use as a cell factory is well-established and it has
      become the most popular expression platform. For this reason, there are many
      molecular tools and protocols at hand for the high-level production of
      heterologous proteins, such as a vast catalog of expression plasmids, a great
      number of engineered strains and many cultivation strategies. We review the
      different approaches for the synthesis of recombinant proteins in E. coli and
      discuss recent progress in this ever-growing field. 

PMID- 24860563
TI  - Eutrophication has no short-term effect on the Cymbastela stipitata holobiont.
AB  - Levels of nitrogen in coastal areas have been rapidly increasing due to
      accumulative inputs of sewage and terrigenous sediments carrying fertilizers.
      Sponges have an immense filtering capacity and may be directly impacted
      (positively or negatively) by elevated concentrations of nitrogen. Sponges also
      host a wide diversity of microbes involved in nitrogen metabolism, yet little is
      known about the effects of nitrogen loading on these symbiotic partnerships.
      Manipulative experiments were undertaken to examine the potential effects of
      excess nitrogen (up to 240 MUM) on microbial symbiosis in the abundant sponge
      species Cymbastela stipitata. Microbial composition and activity were examined
      using 454-pyrotag sequencing of DNA- and RNA-derived samples. Despite the high
      levels of nitrogen exposure (up to 124-fold above ambient), sponges appeared
      visibly unaffected at all treatment concentrations. At the phylum level, the
      microbial community was consistent between all sponge samples regardless of
      nitrogen treatment, with Cyanobacteria and Thaumarchaeota being the dominant
      taxa. Higher microbial diversity was observed at the operational taxonomic units
      (OTU) level (97% sequence similarity), with only 40% of OTUs shared between
      samples from all treatments. However, a single cyanobacterial OTU dominated the
      community of all individuals (average 73.5%) and this OTU did not vary with
      nitrogen treatment. The conserved microbial community in all sponges irrespective
      of nitrogen treatment highlights the stability of the sponge-microbe relationship
      and indicates that the holobiont is resistant to short pulses of nitrogen at
      levels mimicking sewage effluent. 

PMID- 24860562
TI  - Depth-dependent geochemical and microbiological gradients in Fe(III) deposits
      resulting from coal mine-derived acid mine drainage.
AB  - We evaluated the depth-dependent geochemistry and microbiology of sediments that
      have developed via the microbially-mediated oxidation of Fe(II) dissolved in acid
      mine drainage (AMD), giving rise to a 8-10 cm deep "iron mound" that is composed
      primarily of Fe(III) (hydr)oxide phases. Chemical analyses of iron mound
      sediments indicated a zone of maximal Fe(III) reducing bacterial activity at a
      depth of approximately 2.5 cm despite the availability of dissolved O2 at this
      depth. Subsequently, Fe(II) was depleted at depths within the iron mound
      sediments that did not contain abundant O2. Evaluations of microbial communities
      at 1 cm depth intervals within the iron mound sediments using "next generation"
      nucleic acid sequencing approaches revealed an abundance of phylotypes
      attributable to acidophilic Fe(II) oxidizing Betaproteobacteria and the
      chloroplasts of photosynthetic microeukaryotic organisms in the upper 4 cm of the
      iron mound sediments. While we observed a depth-dependent transition in microbial
      community structure within the iron mound sediments, phylotypes attributable to
      Gammaproteobacterial lineages capable of both Fe(II) oxidation and Fe(III)
      reduction were abundant in sequence libraries (comprising >=20% of sequences)
      from all depths. Similarly, abundances of total cells and culturable Fe(II)
      oxidizing bacteria were uniform throughout the iron mound sediments. Our results
      indicate that O2 and Fe(III) reduction co-occur in AMD-induced iron mound
      sediments, but that Fe(II)-oxidizing activity may be sustained in regions of the
      sediments that are depleted in O2. 

PMID- 24860561
TI  - Retrospective and prospective perspectives on zoonotic brucellosis.
AB  - Members of the genus Brucella are pathogenic bacteria exceedingly well adapted to
      their hosts. The bacterium is transmitted by direct contact within the same host
      species or accidentally to secondary hosts, such as humans. Human brucellosis is
      strongly linked to the management of domesticated animals and ingestion of their
      products. Since the domestication of ungulates and dogs in the Fertile Crescent
      and Asia in 12000 and 33000 ya, respectively, a steady supply of well adapted
      emergent Brucella pathogens causing zoonotic disease has been provided. Likewise,
      anthropogenic modification of wild life may have also impacted host
      susceptibility and Brucella selection. Domestication and human influence on wild
      life animals are not neutral phenomena. Consequently, Brucella organisms have
      followed their hosts' fate and have been selected under conditions that favor
      high transmission rate. The "arm race" between Brucella and their preferred hosts
      has been driven by genetic adaptation of the bacterium confronted with the
      evolving immune defenses of the host. Management conditions, such as clustering,
      selection, culling, and vaccination of Brucella preferred hosts have profound
      influences in the outcome of brucellosis and in the selection of Brucella
      organisms. Countries that have controlled brucellosis systematically used
      reliable smooth live vaccines, consistent immunization protocols, adequate
      diagnostic tests, broad vaccination coverage and sustained removal of the
      infected animals. To ignore and misuse tools and strategies already available for
      the control of brucellosis may promote the emergence of new Brucella variants.
      The unrestricted use of low-efficacy vaccines may promote a "false sense of
      security" and works towards selection of Brucella with higher virulence and
      transmission potential. 

PMID- 24860565
TI  - Fungal association with sessile marine invertebrates.
AB  - The presence and association of fungi with sessile marine animals such as coral
      and sponges has been well established, yet information on the extent of diversity
      of the associated fungi is still in its infancy. Culture - as well as metagenomic
      - and transcriptomic-based analyses have shown that fungal presence in
      association with these animals can be dynamic and can include "core" residents as
      well as shifts in fungal communities. Evidence for detrimental and beneficial
      interactions between fungi and their marine hosts is accumulating and current
      challenges include the elucidation of the chemical and cellular crosstalk between
      fungi and their associates within the holobionts. The ecological function of
      fungi in association with sessile marine animals is complex and is founded on a
      combination of factors such as fungal origin, host health, environmental
      conditions and the presence of other resident or invasive microorganisms in the
      host. Based on evidence from the much more studied terrestrial systems, the
      evaluation of marine animal-fungal symbioses under varying environmental
      conditions may well prove to be critical in predicting ecosystem response to
      global change, including effects on the health of sessile marine animals. 

PMID- 24860564
TI  - Antibiotic alternatives: the substitution of antibiotics in animal husbandry?
AB  - It is a common practice for decades to use of sub-therapeutic dose of antibiotics
      in food-animal feeds to prevent animals from diseases and to improve production
      performance in modern animal husbandry. In the meantime, concerns over the
      increasing emergence of antibiotic-resistant bacteria due to the unreasonable use
      of antibiotics and an appearance of less novelty antibiotics have prompted
      efforts to develop so-called alternatives to antibiotics. Whether or not the
      alternatives could really replace antibiotics remains a controversial issue. This
      review summarizes recent development and perspectives of alternatives to
      antibiotics. The mechanism of actions, applications, and prospectives of the
      alternatives such as immunity modulating agents, bacteriophages and their lysins,
      antimicrobial peptides, pro-, pre-, and synbiotics, plant extracts, inhibitors
      targeting pathogenicity (bacterial quorum sensing, biofilm, and virulence), and
      feeding enzymes are thoroughly discussed. Lastly, the feasibility of alternatives
      to antibiotics is deeply analyzed. It is hard to conclude that the alternatives
      might substitute antibiotics in veterinary medicine in the foreseeable future. At
      the present time, prudent use of antibiotics and the establishment of scientific
      monitoring systems are the best and fastest way to limit the adverse effects of
      the abuse of antibiotics and to ensure the safety of animal-derived food and
      environment. 

PMID- 24860566
TI  - Induced pluripotent stem cells: challenges and opportunities for cancer
      immunotherapy.
AB  - Despite recent advances in cancer treatment over the past 30 years, therapeutic
      options remain limited and do not always offer a cure for malignancy. Given that
      tumor-associated antigens (TAA) are, by definition, self-proteins, the need to
      productively engage autoreactive T cells remains at the heart of strategies for
      cancer immunotherapy. These have traditionally focused on the administration of
      autologous monocyte-derived dendritic cells (moDC) pulsed with TAA, or the ex
      vivo expansion and adoptive transfer of tumor-infiltrating lymphocytes (TIL) as a
      source of TAA-specific cytotoxic T cells (CTL). Although such approaches have
      shown some efficacy, success has been limited by the poor capacity of moDC to
      cross present exogenous TAA to the CD8(+) T-cell repertoire and the potential for
      exhaustion of CTL expanded ex vivo. Recent advances in induced pluripotency offer
      opportunities to generate patient-specific stem cell lines with the potential to
      differentiate in vitro into cell types whose properties may help address these
      issues. Here, we review recent success in the differentiation of NK cells from
      human induced pluripotent stem (iPS) cells as well as minor subsets of dendritic
      cells (DCs) with therapeutic potential, including CD141(+)XCR1(+) DC, capable of
      cross presenting TAA to naive CD8(+) T cells. Furthermore, we review recent
      progress in the use of TIL as the starting material for the derivation of iPSC
      lines, thereby capturing their antigen specificity in a self-renewing stem cell
      line, from which potentially unlimited numbers of naive TAA-specific T cells may
      be differentiated, free of the risks of exhaustion. 

PMID- 24860567
TI  - Does the immune system naturally protect against cancer?
AB  - The importance of the immune system in conferring protection against pathogens
      like viruses, bacteria, and parasitic worms is well established. In contrast,
      there is a long-lasting debate on whether cancer prevention is a primary function
      of the immune system. The concept of immunological surveillance of cancer was
      developed by Lewis Thomas and Frank Macfarlane Burnet more than 50 years ago. We
      are still lacking convincing data illustrating immunological eradication of
      precancerous lesions in vivo. Here, I present eight types of evidence in support
      of the cancer immunosurveillance hypothesis. First, primary immunodeficiency in
      mice and humans is associated with increased cancer risk. Second, organ
      transplant recipients, who are treated with immunosuppressive drugs, are more
      prone to cancer development. Third, acquired immunodeficiency due to infection by
      human immunodeficiency virus (HIV-1) leads to elevated risk of cancer. Fourth,
      the quantity and quality of the immune cell infiltrate found in human primary
      tumors represent an independent prognostic factor for patient survival. Fifth,
      cancer cells harbor mutations in protein-coding genes that are specifically
      recognized by the adaptive immune system. Sixth, cancer cells selectively
      accumulate mutations to evade immune destruction ("immunoediting"). Seventh,
      lymphocytes bearing the NKG2D receptor are able to recognize and eliminate
      stressed premalignant cells. Eighth, a promising strategy to treat cancer
      consists in potentiating the naturally occurring immune response of the patient,
      through blockade of the immune checkpoint molecules CTLA-4, PD-1, or PD-L1. Thus,
      there are compelling pieces of evidence that a primary function of the immune
      system is to confer protection against cancer. 

PMID- 24860568
TI  - Controlling the Immunological Crosstalk during Conception and Pregnancy: HLA-G in
      Reproduction.
AB  - In several years after its discovery in the placenta, the human leukocyte antigen
      (HLA) class Ib protein, HLA-G, was not given much attention, nor was it assigned
      great importance. As time has unraveled, HLA-G has proven to have distinctive
      functions and an unforeseen and possibly important role in reproduction. HLA-G is
      characterized mainly by its low polymorphism and restricted tissue distribution
      in non-pathological conditions. In fact, its expression pattern is primarily
      limited to extravillous cytotrophoblast cells at the maternal-fetal interface
      during pregnancy. Due to low polymorphism, almost the same protein is expressed
      by virtually all individuals. It is these unique features that make HLA-G differ
      from its highly polymorphic HLA class Ia counterparts, the HLA-A, -B, and -C
      molecules. Its function, seemingly diverse, is typically receptor-mediated, and
      involves interactions with a wide range of immune cells. As the expression of HLA
      G primarily is limited to gestation, this has given rise to the hypothesis that
      HLA-G plays an important role in the immunological tolerance of the fetus by the
      mother. In keeping with this, it might not be surprising that polymorphisms in
      the HLA-G gene, and levels of HLA-G expression, have been linked to reproductive
      failure and pre-eclampsia. Based on recent studies, we speculate that HLA-G might
      be involved in mechanisms in reproductive immunology even before conception
      because HLA-G can be detected in the genital tract and in the blood of non
      pregnant women, and is present in seminal fluid from men. In addition, HLA-G
      expression has been found in the pre-implanted embryo. Therefore, we propose that
      a combined contribution from the mother, the father, and the embryo/fetus is
      likely to be important. Furthermore, this review presents important aspects of
      HLA-G in relation to reproduction: from genetics to physiological effects, from
      pregnancy and pregnancy complications to a short discussion on future possible
      means of preventative measures and therapy. 

PMID- 24860569
TI  - Modulation of Respiratory TLR3-Anti-Viral Response by Probiotic Microorganisms:
      Lessons Learned from Lactobacillus rhamnosus CRL1505.
AB  - Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract
      illness in infants and young children. Host immune response is implicated in both
      protective and immunopathological mechanisms during RSV infection. Activation of
      Toll-like receptor (TLR)-3 in innate immune cells by RSV can induce airway
      inflammation, protective immune response, and pulmonary immunopathology. A clear
      understanding of RSV-host interaction is important for the development of novel
      and effective therapeutic strategies. Several studies have centered on whether
      probiotic microorganisms with the capacity to stimulate the immune system
      (immunobiotics) might sufficiently stimulate the common mucosal immune system to
      improve defenses in the respiratory tract. In this regard, it was demonstrated
      that some orally administered immunobiotics do have the ability to stimulate
      respiratory immunity and increase resistance to viral infections. Moreover,
      during the last decade scientists have significantly advanced in the knowledge of
      the cellular and molecular mechanisms involved in the protective effect of
      immunobiotics in the respiratory tract. This review examines the most recent
      advances dealing with the use of immunobiotic bacteria to improve resistance
      against viral respiratory infections. More specifically, the article discuss the
      mechanisms involved in the capacity of the immunobiotic strain Lactobacillus
      rhamnosus CRL1505 to modulate the TLR3-mediated immune response in the
      respiratory tract and to increase the resistance to RSV infection. In addition,
      we review the role of interferon (IFN)-gamma and interleukin (IL)-10 in the
      immunoregulatory effect of the CRL1505 strain that has been successfully used for
      reducing incidence and morbidity of viral airways infections in children. 

PMID- 24860570
TI  - Generation of individual diversity: a too neglected fundamental property of
      adaptive immune system.
AB  - The fitness gains resulting from development of the adaptive immune system (AIS)
      during evolution are still the subject of hot debate. A large random repertoire
      of antigenic receptors is costly to develop and could be the source of autoimmune
      reactions. And yet, despite their drawbacks, AIS-like systems seem to have been
      independently acquired in several phyla of metazoans with very different
      anatomies, longevities, and lifestyles. This article is a speculative attempt to
      explore the selective pressures, which favored this striking convergent
      evolution. It is well known that the AIS enables an organism to produce a
      specific immune response against all natural or artificial antigenic structures.
      However, it is frequently neglected that this response is highly variable among
      individuals. In practice, each individual possesses a "private" adaptive immune
      repertoire. This individualization of immune defenses implies that invasion and
      escape immune mechanisms developed by pathogens will certainly not always be
      successful as the specific targets and organization of the immune response are
      somewhat unpredictable. In a population, where individuals display heterogeneous
      immune responses to infection, the probability that a pathogen is able to infect
      all individuals could be reduced compared to a homogeneous population. This
      suggests that the individual diversity of the immune repertoire is not a by
      product of the AIS but of its fundamental properties and could be in part
      responsible for repeated selection and conservation of the AIS during metazoan
      evolution. The capacity of the AIS to improve the management of cooperative or
      parasitic symbiotic relationships at the individual level could be a secondary
      development due to its progressive integration into the innate immune system.
      This hypothesis constitutes a new scenario for AIS emergence and explains the
      selection of MHC restriction and MHC diversification. 

PMID- 24860571
TI  - Control of acute dengue virus infection by natural killer cells.
AB  - Dengue fever is the most important arthropod-borne viral disease worldwide,
      affecting 50-100 million individuals annually. The clinical picture associated
      with acute dengue virus (DENV) infections ranges from classical febrile illness
      to life-threatening disease. The innate immunity is the first line of defense in
      the control of viral replication. This review will examine the particular role of
      natural killer (NK) cells in DENV infection. Over recent years, our understanding
      of the interplay between NK cells and viral pathogenesis has improved
      significantly. NK cells express an array of inhibitory and activating receptors
      that enable them to detect infected targets while sparing normal cells, and to
      recruit adaptive immune cells. To date, the exact mechanism by which NK cells may
      contribute to the control of DENV infection remains elusive. Importantly, DENV
      has acquired mechanisms to evade NK cell responses, further underlining the
      relevance of these cells in pathophysiology. Hence, understanding how NK cells
      affect the outcome of DENV infection could benefit the management of this acute
      disease. 

PMID- 24860572
TI  - Indirectly Recognized HLA-C Mismatches and Their Potential Role in Transplant
      Outcome.
AB  - HLA-C mismatches are clearly associated to alloreactivity after hematopoietic
      stem-cell transplantation; in a number of large cohorts, HLA-C mismatches are
      correlated to an increased risk of acute graft-versus-host disease (GVHD) or even
      impaired survival. While for HLA-A and -B, both antigenic as well as allelic
      mismatches are associated with an increased risk of acute GVHD, such an increased
      risk is only observed for antigenic HLA-C mismatches and not for allelic
      mismatches. These observations raise the question what sets HLA-C apart from HLA
      A and -B. The difference may well be related to the reduced levels of cell
      surface expression of HLA-C as compared to HLA-A and -B, possibly due to, among
      other factors, a limited peptide-binding capacity. This limited peptide-binding
      capacity may retain HLA-C in the ER and enhance degradation of the HLA-C protein.
      Once degraded, HLA-C-derived peptides can be presented to the immune system via
      other HLA alleles and are thus available for indirect recognition. Indeed, such
      HLA-C-derived peptides have previously been eluted from other HLA alleles. We
      have recently developed an approach to predict indirect recognition of HLA
      molecules, by establishing the numbers of predicted indirectly recognizable HLA
      epitopes (PIRCHES). The number of PIRCHES presented on HLA class I and II (PIRCHE
      I and -II, respectively), are highly correlated to clinical measures of
      alloreactivity, such as acute GVHD. In the present "Hypothesis & Theory," we
      reviewed the current knowledge on HLA-C mismatches and alloreactivity. Moreover,
      we speculate about the role of direct and indirect recognition of HLA-C and the
      consequences for donor selection in HLA-C mismatched stem-cell transplantation. 

PMID- 24860573
TI  - Nuclear Receptors and Clearance of Apoptotic Cells: Stimulating the Macrophage's
      Appetite.
AB  - Clearance of apoptotic cells by macrophages occurs as a coordinated process to
      ensure tissue homeostasis. Macrophages play a dual role in this process; first, a
      rapid and efficient phagocytosis of the dying cells is needed to eliminate
      uncleared corpses that can promote inflammation. Second, after engulfment,
      macrophages exhibit an anti-inflammatory phenotype, to avoid unwanted immune
      reactions against cell components. Several nuclear receptors, including liver X
      receptor and proliferator-activated receptor, have been linked to these two
      important features of macrophages during apoptotic cell clearance. This review
      outlines the emerging implications of nuclear receptors in the response of
      macrophages to cell clearance. These include activation of genes implicated in
      metabolism, to process the additional cellular content provided by the engulfed
      cells, as well as inflammatory genes, to maintain apoptotic cell clearance as an
      "immunologically silent" process. Remarkably, genes encoding receptors for the so
      called "eat-me" signals are also regulated by activated nuclear receptors after
      phagocytosis of apoptotic cells, thus enhancing the efficiency of macrophages to
      clear dead cells. 

PMID- 24860574
TI  - Tumor immunotherapy: lessons from autoimmunity.

PMID- 24860577
TI  - Members of the MYBMIXTA-like transcription factors may orchestrate the initiation
      of fiber development in cotton seeds.

PMID- 24860576
TI  - Characterization of T-bet and eomes in peripheral human immune cells.
AB  - The T-box transcription factors T-bet and Eomesodermin (Eomes) have been well
      defined as key drivers of immune cell development and cytolytic function. While
      the majority of studies have defined the roles of these factors in the context of
      murine T-cells, recent results have revealed that T-bet, and possibly Eomes, are
      expressed in other immune cell subsets. To date, the expression patterns of these
      factors in subsets of human peripheral blood mononuclear cells beyond T-cells
      remain relatively uncharacterized. In this study, we used multiparametric flow
      cytometry to characterize T-bet and Eomes expression in major human blood cell
      subsets, including total CD4(+) and CD8(+) T-cells, gammadelta T-cells, invariant
      NKT cells, natural killer cells, B-cells, and dendritic cells. Our studies
      identified novel cell subsets that express T-bet and Eomes and raise implications
      for their possible functions in the context of other human immune cell subsets
      besides their well-known roles in T-cells. 

PMID- 24860575
TI  - Genetically modified organisms and visceral leishmaniasis.
AB  - Vaccination is the most effective method of preventing infectious diseases. Since
      the eradication of small pox in 1976, many other potentially life compromising if
      not threatening diseases have been dealt with subsequently. This event was a
      major leap not only in the scientific world already burdened with many diseases
      but also in the mindset of the common man who became more receptive to novel
      treatment options. Among the many protozoan diseases, the leishmaniases have
      emerged as one of the largest parasite killers of the world, second only to
      malaria. There are three types of leishmaniasis namely cutaneous (CL),
      mucocutaneous (ML), and visceral (VL), caused by a group of more than 20 species
      of Leishmania parasites. Visceral leishmaniasis, also known as kala-azar is the
      most severe form and almost fatal if untreated. Since the first attempts at
      leishmanization, we have killed parasite vaccines, subunit protein, or DNA
      vaccines, and now we have live recombinant carrier vaccines and live attenuated
      parasite vaccines under various stages of development. Although some research has
      shown promising results, many more potential genes need to be evaluated as live
      attenuated vaccine candidates. This mini-review attempts to summarize the success
      and failures of genetically modified organisms used in vaccination against some
      of major parasitic diseases for their application in leishmaniasis. 

PMID- 24860578
TI  - Developing market class specific InDel markers from next generation sequence data
      in Phaseolus vulgaris L.
AB  - Next generation sequence data provides valuable information and tools for genetic
      and genomic research and offers new insights useful for marker development. This
      data is useful for the design of accurate and user-friendly molecular tools.
      Common bean (Phaseolus vulgaris L.) is a diverse crop in which separate
      domestication events happened in each gene pool followed by race and market class
      diversification that has resulted in different morphological characteristics in
      each commercial market class. This has led to essentially independent breeding
      programs within each market class which in turn has resulted in limited within
      market class sequence variation. Sequence data from selected genotypes of five
      bean market classes (pinto, black, navy, and light and dark red kidney) were used
      to develop InDel-based markers specific to each market class. Design of the InDel
      markers was conducted through a combination of assembly, alignment and primer
      design software using 1.6* to 5.1* coverage of Illumina GAII sequence data for
      each of the selected genotypes. The procedure we developed for primer design is
      fast, accurate, less error prone, and higher throughput than when they are
      designed manually. All InDel markers are easy to run and score with no need for
      PCR optimization. A total of 2687 InDel markers distributed across the genome
      were developed. To highlight their usefulness, they were employed to construct a
      phylogenetic tree and a genetic map, showing that InDel markers are reliable,
      simple, and accurate. 

PMID- 24860579
TI  - Comparative phylogenomics of the CBL-CIPK calcium-decoding network in the moss
      Physcomitrella, Arabidopsis, and other green lineages.
AB  - Land plants have evolved a host of anatomical and molecular adaptations for
      terrestrial growth. Many of these adaptations are believed to be elaborations of
      features that were present in their algal-like progenitors. In the model plant
      Arabidopsis, 10 Calcineurin B-Like proteins (CBLs) function as calcium sensors
      and modulate the activity of 26 CBL-Interacting Protein Kinases (CIPKs). The CBL
      CIPK network coordinates environmental responses and helps maintain proper ion
      balances, especially during abiotic stress. We identified and analyzed CBL and
      CIPK homologs in green lineages, including CBLs and CIPKs from charophyte green
      algae, the closest living relatives of land plants. Phylogenomic evidence
      suggests that the network expanded from a small module, likely a single CBL-CIPK
      pair, present in the ancestor of modern plants and algae. Extreme conservation of
      the NAF motif, which mediates CBL-CIPK physical interactions, among all
      identified CIPKs supports the interpretation of CBL and CIPK homologs in green
      algae and early diverging land plants as functionally linked network components.
      We identified the full complement of CBL and CIPK loci in the genome of
      Physcomitrella, a model moss. These analyses demonstrate the strong effects of a
      recent moss whole genome duplication: CBL and CIPK loci appear in cognate pairs,
      some of which appear to be pseudogenes, with high sequence similarity. We cloned
      all full-length transcripts from these loci and performed yeast two-hybrid
      analyses to demonstrate CBL-CIPK interactions and identify specific connections
      within the network. Using phylogenomics, we have identified three ancient types
      of CBLs that are discernible by N-terminal localization motifs and a "green algal
      type" clade of CIPKs with members from Physcomitrella and Arabidopsis. 

PMID- 24860581
TI  - There and back again, or always there? The evolution of rice combined strategy
      for Fe uptake.

PMID- 24860580
TI  - Photosynthetic complex stoichiometry dynamics in higher plants: environmental
      acclimation and photosynthetic flux control.
AB  - The composition of the photosynthetic apparatus of higher plants is dynamically
      adjusted to long-term changes in environmental conditions such as growth light
      intensity and light quality, and to changing metabolic demands for ATP and NADPH
      imposed by stresses and leaf aging. By changing photosynthetic complex
      stoichiometry, a long-term imbalance between the photosynthetic production of ATP
      and NADPH and their metabolic consumption is avoided, and cytotoxic side
      reactions are minimized. Otherwise, an excess capacity of the light reactions,
      relative to the demands of primary metabolism, could result in a disturbance of
      cellular redox homeostasis and an increased production of reactive oxygen
      species, leading to the destruction of the photosynthetic apparatus and the
      initiation of cell death programs. In this review, changes of the abundances of
      the different constituents of the photosynthetic apparatus in response to
      environmental conditions and during leaf ontogenesis are summarized. The
      contributions of the different photosynthetic complexes to photosynthetic flux
      control and the regulation of electron transport are discussed. 

PMID- 24860583
TI  - Transcriptional regulators of Arabidopsis secondary cell wall formation: tools to
      re-program and improve cell wall traits.

PMID- 24860582
TI  - Cytokinin treatments affect the apical-basal patterning of the Arabidopsis
      gynoecium and resemble the effects of polar auxin transport inhibition.
AB  - The apical-basal axis of the Arabidopsis gynoecium is established early during
      development and is divided into four elements from the bottom to the top: the
      gynophore, the ovary, the style, and the stigma. Currently, it is proposed that
      the hormone auxin plays a critical role in the correct apical-basal patterning
      through a concentration gradient from the apical to the basal part of the
      gynoecium, as chemical inhibition of polar auxin transport through 1-N
      naphtylphtalamic acid (NPA) application, severely affects the apical-basal
      patterning of the gynoecium. In this work, we show that the apical-basal
      patterning of gynoecia is also sensitive to exogenous cytokinin (benzyl amino
      purine, BAP) application in a similar way as to NPA. BAP and NPA treatments were
      performed in different mutant backgrounds where either cytokinin perception or
      auxin transport and perception were affected. We observed that cytokinin and
      auxin signaling mutants are hypersensitive to NPA treatment, and auxin transport
      and signaling mutants are hypersensitive to BAP treatment. BAP effects in apical
      basal gynoecium patterning are very similar to the effects of NPA, therefore, it
      is possible that BAP affects auxin transport in the gynoecium. Indeed, not only
      the cytokinin-response TCS::GFP marker, but also the auxin efflux carrier PIN1
      (PIN1::PIN1:GFP) were both affected in BAP-induced valveless gynoecia, suggesting
      that the BAP treatment producing the morphological changes has an impact on both
      in the response pattern to cytokinin and on auxin transport. In summary, we show
      that cytokinin affects proper apical-basal gynoecium patterning in Arabidopsis in
      a similar way to the inhibition of polar auxin transport, and that auxin and
      cytokinin mutants and markers suggest a relation between both hormones in this
      process. 

PMID- 24860584
TI  - Cloning of quantitative trait genes from rice reveals conservation and divergence
      of photoperiod flowering pathways in Arabidopsis and rice.
AB  - Flowering time in rice (Oryza sativa L.) is determined primarily by daylength
      (photoperiod), and natural variation in flowering time is due to quantitative
      trait loci involved in photoperiodic flowering. To date, genetic analysis of
      natural variants in rice flowering time has resulted in the positional cloning of
      at least 12 quantitative trait genes (QTGs), including our recently cloned QTGs,
      Hd17, and Hd16. The QTGs have been assigned to specific photoperiodic flowering
      pathways. Among them, 9 have homologs in the Arabidopsis genome, whereas it was
      evident that there are differences in the pathways between rice and Arabidopsis,
      such that the rice Ghd7-Ehd1-Hd3a/RFT1 pathway modulated by Hd16 is not present
      in Arabidopsis. In this review, we describe QTGs underlying natural variation in
      rice flowering time. Additionally, we discuss the implications of the variation
      in adaptive divergence and its importance in rice breeding. 

PMID- 24860585
TI  - Role of the VirA histidine autokinase of Agrobacterium tumefaciens in the initial
      steps of pathogenesis.
AB  - Histidine kinases serve as critical environmental sensing modules, and despite
      their designation as simple two-component modules, their functional roles are
      remarkably diverse. In Agrobacterium tumefaciens pathogenesis, VirA serves with
      VirG as the initiating sensor/transcriptional activator for inter-kingdom gene
      transfer and transformation of higher plants. Through responses to three separate
      signal inputs, low pH, sugars, and phenols, A. tumefaciens commits to
      pathogenesis in virtually all flowering plants. However, how these three signals
      are integrated to regulate the response and why these signals might be diagnostic
      for susceptible cells across such a broad host-range remains poorly understood.
      Using a homology model of the VirA linker region, we provide evidence for
      coordinated long-range transmission of inputs perceived both outside and inside
      the cell through the creation of targeted VirA truncations. Further, our evidence
      is consistent with signal inputs weakening associations between VirA domains to
      position the active site histidine for phosphate transfer. This mechanism
      requires long-range regulation of inter-domain stability and the transmission of
      input signals through a common integrating domain for VirA signal transduction. 

PMID- 24860586
TI  - The activity of SnRK1 is increased in Phaseolus vulgaris seeds in response to a
      reduced nutrient supply.
AB  - Phaseolus vulgaris seeds can grow and develop at the expense of the pod reserves
      after the fruits have been removed from the plant (Fountain etal., 1989). Because
      this process involves sensing the reduction of nutrients and the remobilisation
      of pod reserves, we investigated the effect on sucrose non-fermenting related
      kinase 1 (SnRK1) activity during this process. Bean fruits removed from the plant
      at 20 days after flowering (DAF) demonstrated active remobilisation of nutrients
      from the pod to the seeds. After 5 days, the pod dry weight was reduced by 50%.
      The process was characterized by a rapid degradation of starch, with the greatest
      decrease observed on day 1 after the fruits were removed. The pod nutrients were
      insufficient for the needs of all the seeds, and only some seeds continued their
      development. Those seeds exhibited a transient reduction in sucrose levels on day
      1 after the fruits were removed. However, the normal level of sucrose was
      recovered, and the rate of starch synthesis was identical to that of a seed
      developed under normal conditions. Removing the fruits from the plant had no
      effect on the activity of SnRK1 in the pods, whereas in the seeds, the activity
      was increased by 35%. Simultaneously, a large reduction in seed sucrose levels
      was observed. The increase in SnRK1 activity was observed in both the cotyledon
      and embryo axes, but it was higher in the cotyledon. At 20-25 DAF, cotyledons
      actively accumulate storage materials. It is possible that the increase in SnRK1
      activity observed in seeds developed in fruits that have been removed from the
      plant is part of the mechanism required for nutrient remobilisation under
      conditions of stress. 

PMID- 24860587
TI  - Quantification of amylose, amylopectin, and beta-glucan in search for genes
      controlling the three major quality traits in barley by genome-wide association
      studies.
AB  - Genome-wide association studies (GWAS) for amylose, amylopectin and beta-glucan
      concentration in a collection of 254 European spring barley varieties allowed to
      identify 20, 17, and 21 single nucleotide polymorphic (SNP) markers,
      respectively, associated with these important grain quality traits. Negative
      correlations between the content of amylose and beta-glucan (R = -0.62, P < 0.01)
      and amylopectin and beta-glucan (R = -0.487, P < 0.01) were found in this large
      collection of spring barley varieties. Besides HvCslF6, amo1 and AGPL2, sex6, and
      waxy were identified among the major genes responsible for beta-glucan, amylose
      and amylopectin content, respectively. Several minor genes like HvGSL4, HvGSL3,
      and HvCesA6, PWD were also detected by GWAS for the first time. Furthermore, the
      gene encoding beta-fructofuranosidase, located on the short arm of chromosome 7H
      at 1.49 cM, and SRF6, encoding "leucine-rich repeat receptor kinase protein" on
      chromosome 2 H, are proposed to be new candidate genes for amylopectin formation
      in barley endosperm. Several of the associated SNPs on chromosome 1, 5, 6, and 7H
      mapped to overlapping regions containing QTLs and genes controlling the three
      grain constituents. In particular chromosomes 5 and 7H carry many QTLs
      controlling barley grain quality. Amylose, amylopectin and beta-glucan were
      interacted among each other through a metabolic network connected by UDP showing
      pleiotropic effects. Taken together, these results showed that cereal quality
      traits related each other and regulated through an interaction network, the
      identified major genes and genetic regions for amylose, amylopectin and beta
      glucan is a helpful for further research on carbohydrates and barley breeding. 

PMID- 24860589
TI  - A simple method suitable to study de novo root organogenesis.
AB  - De novo root organogenesis is the process in which adventitious roots regenerate
      from detached or wounded plant tissues or organs. In tissue culture, appropriate
      types and concentrations of plant hormones in the medium are critical for
      inducing adventitious roots. However, in natural conditions, regeneration from
      detached organs is likely to rely on endogenous hormones. To investigate the
      actions of endogenous hormones and the molecular mechanisms guiding de novo root
      organogenesis, we developed a simple method to imitate natural conditions for
      adventitious root formation by culturing Arabidopsis thaliana leaf explants on B5
      medium without additive hormones. Here we show that the ability of the leaf
      explants to regenerate roots depends on the age of the leaf and on certain
      nutrients in the medium. Based on these observations, we provide examples of how
      this method can be used in different situations, and how it can be optimized.
      This simple method could be used to investigate the effects of various
      physiological and molecular changes on the regeneration of adventitious roots. It
      is also useful for tracing cell lineage during the regeneration process by
      differential interference contrast observation of beta-glucuronidase staining,
      and by live imaging of proteins labeled with fluorescent tags. 

PMID- 24860588
TI  - Composition and function of P bodies in Arabidopsis thaliana.
AB  - mRNA accumulation is tightly regulated by diverse molecular pathways. The
      identification and characterization of enzymes and regulatory proteins involved
      in controlling the fate of mRNA offers the possibility to broaden our
      understanding of posttranscriptional gene regulation. Processing bodies (P
      bodies, PB) are cytoplasmic protein complexes involved in degradation and
      translational arrest of mRNA. Composition and dynamics of these subcellular
      structures have been studied in animal systems, yeasts and in the model plant
      Arabidopsis. Their assembly implies the aggregation of specific factors related
      to decapping, deadenylation, and exoribonucleases that operate synchronously to
      regulate certain mRNA targets during development and adaptation to stress.
      Although the general function of PB along with the flow of genetic information is
      understood, several questions still remain open. This review summarizes data on
      the composition, potential molecular roles, and biological significance of PB and
      potentially related proteins in Arabidopsis. 

PMID- 24860591
TI  - Imputation of TPMT defective alleles for the identification of patients with high
      risk phenotypes.
AB  - BACKGROUND: The activity of thiopurine methyltransferase (TPMT) is subject to
      genetic variation. Loss-of-function alleles are associated with various degrees
      of myelosuppression after treatment with thiopurine drugs, thus genotype-based
      dosing recommendations currently exist. The aim of this study was to evaluate the
      potential utility of leveraging genomic data from large biorepositories in the
      identification of individuals with TPMT defective alleles. MATERIAL AND METHODS:
      TPMT variants were imputed using the 1000 Genomes Project reference panel in
      87,979 samples from the biobank at The Children's Hospital of Philadelphia.
      Population ancestry was determined by principal component analysis using HapMap3
      samples as reference. Frequencies of the TPMT imputed alleles, genotypes and the
      associated phenotype were determined across the different populations. A sample
      of 630 subjects with genotype data from Sanger sequencing (N = 59) and direct
      genotyping (N = 583) (12 samples overlapping in the two groups) was used to check
      the concordance between the imputed and observed genotypes, as well as the
      sensitivity, specificity and positive and negative predictive values of the
      imputation. RESULTS: Two SNPs (rs1800460 and rs1142345) that represent three TPMT
      alleles ((*)3A, (*)3B, and (*)3C) were imputed with adequate quality. Frequency
      for the associated enzyme activity varied across populations and 89.36-94.58%
      were predicted to have normal TPMT activity, 5.3-10.31% intermediate and 0.12
      0.34% poor activities. Overall, 98.88% of individuals (623/630) were correctly
      imputed into carrying no risk alleles (553/553), heterozygous (45/46) and
      homozygous (25/31). Sensitivity, specificity and predictive values of imputation
      were over 90% in all cases except for the sensitivity of imputing homozygous
      subjects that was 80.64%. CONCLUSION: Imputation of TPMT alleles from existing
      genomic data can be used as a first step in the screening of individuals at risk
      of developing serious adverse events secondary to thiopurine drugs.

PMID- 24860590
TI  - Worming forward: amyotrophic lateral sclerosis toxicity mechanisms and genetic
      interactions in Caenorhabditis elegans.
AB  - Neurodegenerative diseases share pathogenic mechanisms at the cellular level
      including protein misfolding, excitotoxicity and altered RNA homeostasis among
      others. Recent advances have shown that the genetic causes underlying these
      pathologies overlap, hinting at the existence of a genetic network for
      neurodegeneration. This is perhaps best illustrated by the recent discoveries of
      causative mutations for amyotrophic lateral sclerosis (ALS) and frontotemporal
      degeneration (FTD). Once thought to be distinct entities, it is now recognized
      that these diseases exist along a genetic spectrum. With this wealth of
      discoveries comes the need to develop new genetic models of ALS and FTD to
      investigate not only pathogenic mechanisms linked to causative mutations, but to
      uncover potential genetic interactions that may point to new therapeutic targets.
      Given the conservation of many disease genes across evolution, Caenorhabditis
      elegans is an ideal system to investigate genetic interactions amongst these
      genes. Here we review the use of C. elegans to model ALS and investigate a
      putative genetic network for ALS/FTD that may extend to other neurological
      disorders. 

PMID- 24860593
TI  - Penalized regression approaches to testing for quantitative trait-rare variant
      association.
AB  - In statistical data analysis, penalized regression is considered an attractive
      approach for its ability of simultaneous variable selection and parameter
      estimation. Although penalized regression methods have shown many advantages in
      variable selection and outcome prediction over other approaches for high
      dimensional data, there is a relative paucity of the literature on their
      applications to hypothesis testing, e.g., in genetic association analysis. In
      this study, we apply several new penalized regression methods with a novel
      penalty, called Truncated L1 -penalty (TLP) (Shen et al., 2012), for either
      variable selection, or both variable selection and parameter grouping, in a data
      adaptive way to test for association between a quantitative trait and a group of
      rare variants. The performance of the new methods are compared with some existing
      tests, including some recently proposed global tests and penalized regression
      based methods, via simulations and an application to the real sequence data of
      the Genetic Analysis Workshop 17 (GAW17). Although our proposed penalized methods
      can improve over some existing penalized methods, often they do not outperform
      some existing global association tests. Some possible problems with utilizing
      penalized regression methods in genetic hypothesis testing are discussed. Given
      the capability of penalized regression in selecting causal variants and its
      sometimes promising performance, further studies are warranted. 

PMID- 24860592
TI  - Haplotype association analysis of combining unrelated case-control and triads
      with consideration of population stratification.
AB  - Combining data when data are collected under different study designs, such as
      family trios and unrelated case-control samples, gains more power and is cost
      effective than analyzing each data separately. However, a potential concern is
      population stratification (PS) among unrelated case-control samples and analyses
      integrating data should address this confounding effect. In this paper, we
      develop a simpler method, haplotype generalized linear model (HGLM), that tests
      and estimates haplotype effects on disease risk and allows for modification
      against PS for combining data. We proposed to combine information across
      aggregations of haplotype weighted-counts estimated from population case-control
      data and trio data separately, and to perform subsequent GLM analysis.
      Furthermore, we present a framework of analysis of variance based on haplotype
      weighted-counts for detecting whether it is appropriate to combine two data
      sources, as well as the modified HGLM with clustering methods for addressing PS.
      We evaluate the statistical properties in terms of the accuracy, false positive
      rate (FPR) and empirical power using simulated data with regard to various
      disease risks, sample sizes, multi-SNP haplotypes and the presence of PS. Our
      simulation results indicate that HGLM performs comparably well with the
      likelihood-based haplotype association analysis, particularly when the haplotype
      effects are moderate, but may not perform well when dealing with lengthy
      haplotypes for small sample sizes. In the presence of PS, the modified HGLM
      remains valid and has satisfactory nominal level and small bias. Overall, HGLM
      appears to be successful in combining data and is simple to implement in standard
      statistical software. 

PMID- 24860595
TI  - Exploring genome wide bisulfite sequencing for DNA methylation analysis in
      livestock: a technical assessment.
AB  - Recent advances made in "omics" technologies are contributing to a revolution in
      livestock selection and breeding practices. Epigenetic mechanisms, including DNA
      methylation are important determinants for the control of gene expression in
      mammals. DNA methylation research will help our understanding of how
      environmental factors contribute to phenotypic variation of complex production
      and health traits. High-throughput sequencing is a vital tool for the
      comprehensive analysis of DNA methylation, and bisulfite-based strategies coupled
      with DNA sequencing allows for quantitative, site-specific methylation analysis
      at the genome level or genome wide. Reduced representation bisulfite sequencing
      (RRBS) and more recently whole genome bisulfite sequencing (WGBS) have proven to
      be effective techniques for studying DNA methylation in both humans and mice.
      Here we report the development of RRBS and WGBS for use in sheep, the first
      application of this technology in livestock species. Important technical issues
      associated with these methodologies including fragment size selection and
      sequence depth are examined and discussed. 

PMID- 24860594
TI  - Testing GxG interactions between coinfecting microbial parasite genotypes within
      hosts.
AB  - Host-parasite interactions represent one of the strongest selection pressures in
      nature. They are often governed by genotype-specific (GxG) interactions resulting
      in host genotypes that differ in resistance and parasite genotypes that differ in
      virulence depending on the antagonist's genotype. Another type of GxG
      interactions, which is often neglected but which certainly influences host
      parasite interactions, are those between coinfecting parasite genotypes.
      Mechanistically, within-host parasite interactions may range from competition for
      limited host resources to cooperation for more efficient host exploitation. The
      exact type of interaction, i.e., whether competitive or cooperative, is known to
      affect life-history traits such as virulence. However, the latter has been shown
      for chosen genotype combinations only, not considering whether the specific
      genotype combination per se may influence the interaction (i.e., GxG
      interactions). Here, we want to test for the presence of GxG interactions between
      coinfections of the bacterium Bacillus thuringiensis infecting the nematode
      Caenorhabditis elegans by combining two non-pathogenic and five pathogenic
      strains in all possible ways. Furthermore, we evaluate whether the type of
      interaction, reflected by the direction of virulence change of multiple compared
      to single infections, is genotype-specific. Generally, we found no indication for
      GxG interactions between non-pathogenic and pathogenic bacterial strains,
      indicating that virulence of pathogenic strains is equally affected by both non
      pathogenic strains. Specific genotype combinations, however, differ in the
      strength of virulence change, indicating that the interaction type between
      coinfecting parasite strains and thus the virulence mechanism is specific for
      different genotype combinations. Such interactions are expected to influence host
      parasite interactions and to have strong implications for coevolution. 

PMID- 24860597
TI  - AlienTrimmer removes adapter oligonucleotides with high sensitivity in short
      insert paired-end reads. Commentary on Turner (2014) Assessment of insert sizes
      and adapter content in FASTQ data from NexteraXT libraries.

PMID- 24860596
TI  - Modeling conformational transitions in kinases by molecular dynamics simulations:
      achievements, difficulties, and open challenges.
AB  - Protein kinases work because their flexibility allows to continuously switch from
      inactive to active form. Despite the large number of structures experimentally
      determined in such states, the mechanism of their conformational transitions as
      well as the transition pathways are not easily to capture. In this regard,
      computational methods can help to shed light on such an issue. However, due to
      the intrinsic sampling limitations, much efforts have been done to model in a
      realistic way the conformational changes occurring in protein kinases. In this
      review we will address the principal biological achievements and structural
      aspects in studying kinases conformational transitions and will focus on the main
      challenges related to computational approaches such as molecular modeling and MD
      simulations. 

PMID- 24860599
TI  - Molecular mechanisms for the inheritance of acquired characteristics-exosomes,
      microRNA shuttling, fear and stress: Lamarck resurrected?

PMID- 24860598
TI  - Non-coding RNAs in pluripotency and neural differentiation of human pluripotent
      stem cells.
AB  - Several studies have demonstrated the important role of non-coding RNAs as
      regulators of posttranscriptional processes, including stem cells self-renewal
      and neural differentiation. Human embryonic stem cells (hESCs) and induced
      pluripotent stem cells (ihPSCs) show enormous potential in regenerative medicine
      due to their capacity to differentiate to virtually any type of cells of human
      body. Deciphering the role of non-coding RNAs in pluripotency, self-renewal and
      neural differentiation will reveal new molecular mechanisms involved in induction
      and maintenances of pluripotent state as well as triggering these cells toward
      clinically relevant cells for transplantation. In this brief review we will
      summarize recently published studies which reveal the role of non-coding RNAs in
      pluripotency and neural differentiation of hESCs and ihPSC. 

PMID- 24860600
TI  - DNA, statistics and the law: a cross-disciplinary approach to forensic inference.

PMID- 24860602
TI  - Analysis of pull-in instability of geometrically nonlinear microbeam using radial
      basis artificial neural network based on couple stress theory.
AB  - The static pull-in instability of beam-type microelectromechanical systems (MEMS)
      is theoretically investigated. Two engineering cases including cantilever and
      double cantilever microbeam are considered. Considering the midplane stretching
      as the source of the nonlinearity in the beam behavior, a nonlinear size
      dependent Euler-Bernoulli beam model is used based on a modified couple stress
      theory, capable of capturing the size effect. By selecting a range of geometric
      parameters such as beam lengths, width, thickness, gaps, and size effect, we
      identify the static pull-in instability voltage. A MAPLE package is employed to
      solve the nonlinear differential governing equations to obtain the static pull-in
      instability voltage of microbeams. Radial basis function artificial neural
      network with two functions has been used for modeling the static pull-in
      instability of microcantilever beam. The network has four inputs of length,
      width, gap, and the ratio of height to scale parameter of beam as the independent
      process variables, and the output is static pull-in voltage of microbeam.
      Numerical data, employed for training the network, and capabilities of the model
      have been verified in predicting the pull-in instability behavior. The output
      obtained from neural network model is compared with numerical results, and the
      amount of relative error has been calculated. Based on this verification error,
      it is shown that the radial basis function of neural network has the average
      error of 4.55% in predicting pull-in voltage of cantilever microbeam. Further
      analysis of pull-in instability of beam under different input conditions has been
      investigated and comparison results of modeling with numerical considerations
      shows a good agreement, which also proves the feasibility and effectiveness of
      the adopted approach. The results reveal significant influences of size effect
      and geometric parameters on the static pull-in instability voltage of MEMS. 

PMID- 24860605
TI  - Pathologic Outcomes following Urethral Diverticulectomy in Women.
AB  - Purpose. Although most urethral diverticula in women are benign, there is a
      subset of patients who develop malignant changes. Limited studies report the
      pathologic findings associated with this relatively rare entity. We describe the
      clinicopathologic findings of women who underwent urethral diverticulectomy.
      Methods. A consecutive series of 29 women who underwent surgical resection of a
      urethral diverticulum were identified between 1992 and 2013. Clinical and
      radiographic data was collected by retrospective review of patient medical
      records. All pathological slides were rereviewed by a single urologic
      pathologist. Results. Of the 14 women with clinical data, 9 (64%) presented with
      urgency, 7 (50%) with urinary frequency, 3 (21%) with urinary incontinence, and 3
      (21%) with dysuria. Mean diverticular size was 2.3 (+/-1.4) cm. Although one
      patient (3%) had invasive adenocarcinoma on final pathology, the remaining 28
      cases (97%) demonstrated benign features. The most common findings were
      inflammation (55%) and nephrogenic adenoma (21%). Conclusions. Although most
      urethral diverticula in women are benign, there is a subset of patients who
      develop malignancy in association with the diverticulum. In this series, 97% of
      cases had a benign histology. These findings are important when counseling
      patients regarding treatment options. 

PMID- 24860601
TI  - The Sac domain-containing phosphoinositide phosphatases: structure, function, and
      disease.
AB  - Phosphoinositides (PIs) have long been known to have an essential role in cell
      physiology. Their intracellular localization and concentration must be tightly
      regulated for their proper function. This spatial and temporal regulation is
      achieved by a large number of PI kinases and phosphatases that are present
      throughout eukaryotic species. One family of these enzymes contains a conserved
      PI phosphatase domain termed Sac. Although the Sac domain is homologous among
      different Sac domain-containing proteins, all appear to exhibit varied substrate
      specificity and subcellular localization. Dysfunctions in several members of this
      family are implicated in a range of human diseases such as cardiac hypertrophy,
      bipolar disorder, Down's syndrome, Charcot-Marie-Tooth disease (CMT) and
      Amyotrophic Lateral Sclerosis (ALS). In plant, several Sac domain-containing
      proteins have been implicated in the stress response, chloroplast function and
      polarized secretion. In this review, we focus on recent findings in the family of
      Sac domain-containing PI phosphatases in yeast, mammal and plant, including the
      structural analysis into the mechanism of enzymatic activity, cellular functions,
      and their roles in disease pathophysiology.

PMID- 24860604
TI  - Synchronized dual pulse gastric electrical stimulation induces activation of
      enteric glial cells in rats with diabetic gastroparesis.
AB  - Objective. The aims of this study were to investigate the effects of synchronized
      dual pulse gastric electrical stimulation (SGES) on gastric motility in different
      periods for diabetic rats and try to explore the possible mechanisms of the
      effects. Methods. Forty-six rats were used in the study. Gastric slow waves were
      recorded at baseline, 7-14-day diabetes and 56-63-day diabetes before and after
      stimulation and the age-matched control groups. SGES-60 mins and SGES-7 days (60
      mins/day) were performed to test the effects on gastric motility and to evaluate
      glial marker S100B expression in stomach. Results. (1) Gastric emptying was
      accelerated in 7-14-day diabetes and delayed in 56-63-day diabetes. (2) The S100B
      expression in 56-63-day diabetes decreased and the ultrastructure changed. (3)
      The age-associated loss of EGC was observed in 56-63-day control group. (4) SGES
      was able to not only accelerate gastric emptying but also normalize gastric slow
      waves. (5) The S100B expression increased after SGES and the ultrastructure of
      EGC was partially restored. The effect of SGES-7 days was superior to SGES-60
      mins. Conclusions. Delayed gastric emptying due to the growth of age may be
      related to the EGC inactivation. The effects of the SGES on gastric motility may
      be associated with EGC activation. 

PMID- 24860606
TI  - Serotypes and Antimicrobial Resistance of Human Nontyphoidal Isolates of
      Salmonella enterica from Crete, Greece.
AB  - We report on the serotype distribution and the antimicrobial resistance patterns
      to 20 different antimicrobials of 150 Salmonella enterica strains isolated from
      stools of diarrhoeal patients on the island of Crete over the period January 2011
      December 2012. Among the S. enterica serotypes recovered, Enteritidis was the
      most prevalent (37.3%), followed by Typhimurium (28.7%) and Newport (8.7%). No
      resistance was detected to extended-spectrum cephalosporins and carbapenems.
      Rates of resistance to ampicillin, amoxicillin/clavulanic acid, chloramphenicol,
      tetracycline, and cotrimoxazole were 9.3%, 4%, 2%, 15.3%, and 8.7%, respectively.
      Resistance to >=4 antibiotics was primarily observed for serotypes Typhimurium
      and Hadar. Enteritidis remains the predominant serotype in Crete. Although low
      resistance to most antimicrobials was detected, continued surveillance of
      susceptibility is needed due to the risk of resistance. 

PMID- 24860608
TI  - Multiple-allergen oral immunotherapy improves quality of life in caregivers of
      food-allergic pediatric subjects.
AB  - BACKGROUND: Food allergy (FA) negatively affects quality of life in caregivers of
      food-allergic children, imposing a psychosocial and economic burden. Oral
      immunotherapy (OIT) is a promising investigational therapy for FA. However, OIT
      can be a source of anxiety as it carries risk for allergic reactions. The effect
      of OIT with multiple food allergens (mOIT) on FA-specific health-related quality
      of life (HRQL) has never been studied in participants with multiple, severe food
      allergies. This study is the first to investigate the effects of mOIT on FA
      related HRQL in caregivers of pediatric subjects. METHODS: Caregiver HRQL was
      assessed using a validated Food Allergy Quality of Life - Parental Burden (FAQL
      PB) Questionnaire (J Allergy Clin Immunol 114(5):1159-1163, 2004). Parents of
      participants in two single-center Phase I clinical trials receiving mOIT (n = 29)
      or rush mOIT with anti-IgE (omalizumab) pre-treatment (n = 11) completed the FAQL
      PB prior to study intervention and at 2 follow-up time-points (6 months and 18
      months). Parents of subjects not receiving OIT (control group, n = 10) completed
      the FAQL-PB for the same time-points. RESULTS: HRQL improved with clinical
      (change < -0.5) and statistical (p < 0.05) significance in the mOIT group
      (baseline mean 3.9, 95% CI 3.4-4.4; 6-month follow-up mean 2.5, 95% CI 2.0-3.0;
      18-month follow-up mean 1.8, 95% CI 1.4-2.1) and rush mOIT group (baseline mean
      3.9, 95% CI 3.1-4.7; 6-month follow-up mean 1.7, 95% CI 0.9-2.6; 18-month follow
      up mean 1.3, 95% CI 0.3-2.4). HRQL scores did not significantly change in the
      control group (n = 10). CONCLUSION: Multi-allergen OIT with or without omalizumab
      leads to improvement in caregiver HRQL, suggesting that mOIT can help relieve the
      psychosocial and economic burden FA imposes on caregivers of food-allergic
      children.

PMID- 24860607
TI  - Fall in Vitamin D Levels during Hospitalization in Children.
AB  - Plasma levels of 25-hydroxyvitamin D [25(OH)D] were measured by competitive
      Electrochemiluminescence Immunoassay (ECLIA) in 92 children (67 boys, 25 girls)
      aged 3 months to 12 years at admission to hospital (timepoint 1, T1) and at
      discharge (timepoint 2, T2). There was a significant fall in the mean 25(OH)D
      from T1 (71.87 +/- 27.25 nmol/L) to T2 (49.03 +/- 22.25 nmol/L) (mean change =
      22.84 nmol/L, P value = 0.0004). Proportion of patients having VDD (levels <50
      nmol/L) at admission (25%, 23/92) increased significantly at the time of
      discharge (51.09%, 47/92) (P = 0.0004). There was a trend towards longer duration
      of hospital stay, requirement of ventilation and inotropes, development of
      healthcare-associated infection, and mortality in vitamin D deficient as compared
      to nondeficient patients though the difference was statistically insignificant.
      In conclusion, vitamin D levels fall significantly and should be monitored during
      hospital stay in children. Large clinical studies are needed to prospectively
      evaluate the effect of vitamin D supplementation in vitamin D deficient
      hospitalized children on various disease outcome parameters. 

PMID- 24860609
TI  - Ethanolic Extract of Butea monosperma Leaves Elevate Blood Insulin Level in Type
      2 Diabetic Rats, Stimulate Insulin Secretion in Isolated Rat Islets, and Enhance
      Hepatic Glycogen Formation.
AB  - We measured a vast range of parameters, in an attempt to further elucidate
      previously claimed antihyperglycemic activity of Butea monosperma. Our study
      clearly negates the possibility of antidiabetic activity by inhibited
      gastrointestinal enzyme action or by reduced glucose absorption. Reduction of
      fasting and postprandial glucose level was reconfirmed (P < 0.05). Improved serum
      lipid profile via reduced low density lipoprotein (LDL), cholesterol,
      triglycerides (TG), and increased high density lipoprotein (HDL) was also
      reestablished (P < 0.05). Significant insulin secretagogue activity of B.
      monosperma was found in serum insulin assay of B. monosperma treated type 2
      diabetic rats (P < 0.01). This was further ascertained by our study on insulin
      secretion on isolated rat islets (P < 0.05). Improved sensitivity of glucose was
      shown by the significant increase in hepatic glycogen deposition (P < 0.05).
      Hence, we concluded that antihyperglycemic activity of B. monosperma was mediated
      by enhanced insulin secretion and enhanced glycogen formation in the liver. 

PMID- 24860610
TI  - Antibody responses to intradermal or intramuscular MF59-adjuvanted influenza
      vaccines as evaluated in elderly institutionalized volunteers during a season of
      partial mismatching between vaccine and circulating A(H3N2) strains.
AB  - BACKGROUND: The age-related weakening of the immune system makes elderly subjects
      less responsive to influenza vaccination. In the last years, two "enhanced
      vaccines" were licensed for individuals aged >=65 years, one being a subunit
      vaccine (Fluad(r)) containing the MF59 adjuvant administered intramuscularly (IM
      MF59) and the other one a split non-adjuvanted vaccine administered intradermally
      (Intanza(r) 15mcg) (ID). In the present study, we evaluated and compared the
      antibody responses against the three vaccine antigens and heterovariant A(H3N2)
      circulating viruses induced by IM-MF59 and ID influenza vaccines in 80 elderly
      institutionalized volunteers (40 per group) during the Winter season 2011-2012.
      RESULTS: Hemagglutination inhibiting (HI) antibody titers were assessed in blood
      samples collected before, 1 and 6 months after vaccination. One month after
      vaccination both the IM-MF59 and ID vaccines induced increases in HI titers
      against all the three vaccine strains. The results in the two groups were similar
      against the A(H3N2) and A(H1N1) strains. Responses against the B strain typically
      tended to be higher after ID than IM-MF59, yet both vaccines stimulated lower
      responses against the B strain than against the two A strains. The two vaccines
      induced favorable results also against four epidemic drifted A(H3N2) viruses
      circulating in Winter 2011-2012. Six months after vaccination, the HI titers
      decreased in both groups. CONCLUSION: The responses induced by IM-MF59 and ID
      vaccines in institutionalized elderly people were similar against the A(H3N2) and
      A(H1N1) strains but frequently higher, for the ID, against the B strain. The two
      vaccines induced positive responses against drifted A(H3N2) circulating viruses.

PMID- 24860611
TI  - Accuracy of the VO2peak prediction equation in firefighters.
AB  - BACKGROUND: A leading contributing factor to firefighter injury and death is lack
      of fitness. Therefore, the Fire Service Joint Labor Management Wellness-Fitness
      Initiative (WFI) was established that includes a focus on providing fitness
      assessments to all fire service personnel. The current fitness assessment
      includes a submaximal exercise test protocol and associated prediction equation
      to predict individual VO2peak as a measure of fitness. There is limited
      information on the accuracy, precision, and sources of error of this prediction
      equation. This study replicated previous research by validating the accuracy of
      the WFI VO2peak prediction equation for a group of firefighters and further
      examining potential sources of error for an individual firefighters' assessment.
      METHODS: The sample consisted of 22 firefighters who completed a maximal exercise
      test protocol similar to the WFI submaximal protocol, but the test was terminated
      when firefighters reached a maximal level of exertion (i.e., measured VO2peak).
      We then calculated the predicted VO2peak based on the WFI prediction equation
      along with individual firefighters' body mass index (BMI) and 85% of maximum
      heart rate. The data were analyzed using paired samples t-tests in SPSS v. 21.0.
      RESULTS: The difference between predicted and measured VO2peak was -0.77 +/- 8.35
      mL*kg(-1)*min(-1). However, there was a weak, statistically non-significant
      association between measured VO2peak and predicted VO2peak (R(2) = 0.09, F(1,21)
      = 2.05, p = 0.17). The intraclass correlation coefficient (ICC = 0.215, p > 0.05)
      and Pearson (r = 0.31, p = 0.17) and Spearman (rho = 0.28, p = 0.21) correlation
      coefficients were small. The standard error of the estimate (SEE) was 8.5 mL*kg(
      1)*min(-1). Further, both age and baseline fitness level were associated with
      increased inaccuracy of the prediction equation. CONCLUSIONS: We provide data on
      the inaccuracy and sources of error for the WFI VO2peak prediction equation for
      predicting fitness level in individual firefighters, despite apparently accurate
      predictions for a group of firefighters. These results suggest that the WFI
      prediction equation may need to be reevaluated as a means of precisely
      determining fitness for individual firefighters, which may affect employment
      status, duty assignment, and overall life safety of the firefighter.

PMID- 24860612
TI  - Infant feeding practices and maternal socio-demographic factors that influence
      practice of exclusive breastfeeding among mothers in Nnewi South-East Nigeria: a
      cross-sectional and analytical study.
AB  - BACKGROUND: Malnutrition is an underlying factor in more than 50% of the major
      cause of infant mortality-Pneumonia, diarrhoeal disease and measles which account
      for 70% of infant mortality. Therefore, programs to promote adequate nutrition
      for age can help reduce mortality from these disease conditions and indispensible
      to achievement of MDG 4. AIM: To describe the feeding practices of infants below
      six months of age and determine maternal socio-demographic factors that
      influences the practice of exclusive breastfeeding (EBF) among mothers in Nnewi,
      south-east Nigeria. METHODS: Four hundred mother-infant pairs attending the
      infant welfare clinic of the Nnamdi Azikiwe University teaching hospital (NAUTH)
      during 2012 were consecutively recruited after meeting the study inclusion
      criteria. Data on breastfeeding were based on infant feeding practice in the
      previous 24 hours. Exclusive breastfeeding was defined as infant feeding with
      only breast milk. RESULTS: Awareness (95.3%) and knowledge (82.0%) of EBF was
      high among surveyed mother but the practice of EBF (33.5%) was very low. Positive
      attitude towards EBF practice was shown by many (71.0%) of surveyed mothers. EBF
      practice decreased with increasing infant age, OR 0.72 (95% CI 0.34, 1.51) for 1
      2 months, OR 0.58 (95% CI 0.23, 1.44) for 3-4 months and OR 0.20 (95% CI 0.06,
      0.73) for 5-6 months compared to infants < 1 month old. Maternal education,
      socioeconomic class, mode of delivery and infants first feed were retained as
      important maternal predictors of EBF practice after adjustment for confounders.
      Decreased likelihood of EBF practice was found among mothers of lower educational
      attainment, OR 0.33 (95% CI 0.13, 0.81), mothers who delivered through caesarean
      section, OR 0.38 (95% CI 0.18, 0.84), mothers of higher socio-economic status
      [(middle class, OR 0.46 (95% CI 0.22, 0.99) and upper class, OR 0.32 (95% CI
      0.14, 0.74)] while increased likelihood of EBF practice was seen in mothers who
      gave their infants breast milk as their first feed, OR 3.36 (95% CI 1.75, 6.66).
      CONCLUSION: Knowledge and awareness does not translate to practice of EBF. More
      effort by health workers and policy makers should be directed to mothers along
      the fault lines to encourage the practice of EBF.

PMID- 24860614
TI  - Mixed-norm regularization for brain decoding.
AB  - This work investigates the use of mixed-norm regularization for sensor selection
      in event-related potential (ERP) based brain-computer interfaces (BCI). The
      classification problem is cast as a discriminative optimization framework where
      sensor selection is induced through the use of mixed-norms. This framework is
      extended to the multitask learning situation where several similar classification
      tasks related to different subjects are learned simultaneously. In this case,
      multitask learning helps in leveraging data scarcity issue yielding to more
      robust classifiers. For this purpose, we have introduced a regularizer that
      induces both sensor selection and classifier similarities. The different
      regularization approaches are compared on three ERP datasets showing the interest
      of mixed-norm regularization in terms of sensor selection. The multitask
      approaches are evaluated when a small number of learning examples are available
      yielding to significant performance improvements especially for subjects
      performing poorly. 

PMID- 24860615
TI  - Coherent terabit communications with microresonator Kerr frequency combs.
AB  - Optical frequency combs have the potential to revolutionize terabit
      communications1. Generation of Kerr combs in nonlinear microresonators2
      represents a particularly promising option3 enabling line spacings of tens of
      GHz. However, such combs may exhibit strong phase noise4-6, which has made high
      speed data transmission impossible up to now. Here we demonstrate that systematic
      adjustment of pump conditions for low phase noise4,7-9 enables coherent data
      transmission with advanced modulation formats that pose stringent requirements on
      the spectral purity of the comb. In a first experiment, we encode a data stream
      of 392 Gbit/s on a Kerr comb using quadrature phase shift keying (QPSK) and 16
      state quadrature amplitude modulation (16QAM). A second experiment demonstrates
      feedback-stabilization of the comb and transmission of a 1.44 Tbit/s data stream
      over up to 300 km. The results show that Kerr combs meet the highly demanding
      requirements of coherent communications and thus offer an attractive solution
      towards chip-scale terabit/s transceivers.

PMID- 24860616
TI  - Predicting aggression in children with ADHD.
AB  - OBJECTIVE: The present study uses structural equation modeling of latent traits
      to examine the extent to which family factors, cognitive factors and perceptions
      of rejection in mother-child relations differentially correlate with aggression
      at home and at school. METHODS: Data were collected from 476 school-age (7-15
      years old) children with a diagnosis of ADHD who had previously shown different
      types of aggressive behavior, as well as from their parents and teachers.
      Structural equation modeling was used to examine the differential relationships
      between maternal rejection, family, cognitive factors and aggression in home and
      school settings. RESULTS: Family factors influenced aggression reported at home
      (.68) and at school (.44); maternal rejection seems to be related to aggression
      at home (.21). Cognitive factors influenced aggression reported at school (.-05)
      and at home (-.12). CONCLUSIONS: Both genetic and environmental factors
      contribute to the development of aggressive behavior in ADHD. Identifying key
      risk factors will advance the development of appropriate clinical interventions
      and prevention strategies and will provide information to guide the targeting of
      resources to those children at highest risk.

PMID- 24860617
TI  - Structure and enzymatic accessibility of leaf and stem from wheat straw before
      and after hydrothermal pretreatment.
AB  - BACKGROUND: Biomass recalcitrance is affected by a number of chemical, physical
      and biological factors. In this study we looked into the differences in
      recalcitrance between two major anatomical fractions of wheat straw biomass, leaf
      and stem. A set of twenty-one wheat cultivars was fractionated and illustrated
      the substantial variation in leaf-to-stem ratio between cultivars. The two
      fractions were compared in terms of chemical composition, enzymatic
      convertibility, cellulose crystallinity and glucan accessibility. The use of
      water as a probe for assessing glucan accessibility was explored using low field
      nuclear magnetic resonance and infrared spectroscopy in combination with hydrogen
      deuterium exchange. RESULTS: Leaves were clearly more degradable by
      lignocellulolytic enzymes than stems, and it was demonstrated that xylose removal
      was more linked to glucose yield for stems than for leaves. Comparing the
      locations of water in leaf and stem by low field NMR and FT-IR revealed that the
      glucan hydroxyl groups in leaves were more accessible to water than glucan
      hydroxyl groups in stems. No difference in crystallinity between leaf and stem
      was observed using wide angle x-ray diffraction. Hydrothermal pretreatment
      increased the accessibility towards water in stems but not in leaves. The results
      in this study indicate a correlation between the accessibility of glucan to water
      and to enzymes. CONCLUSIONS: Enzymatic degradability of wheat straw anatomical
      fractions can be indicated by the accessibility of the hydroxyl groups to water.
      This suggests that water may be used to assess glucan accessibility in biomass
      samples.

PMID- 24860613
TI  - Genetic risk, ethnic variations and pharmacogenetic biomarkers in age-related
      macular degeneration and polypoidal choroidal vasculopathy.

PMID- 24860618
TI  - Prevalence of burnout syndrome in clinical nurses at a hospital of excellence.
AB  - BACKGROUND: Burnout syndrome can be defined as long-term work stress resulting
      from the interaction between constant emotional pressure associated with intense
      interpersonal involvement for long periods of time and personal characteristics.
      We investigated the prevalence/propensity of Burnout syndrome in clinical nurses,
      and the factors related to Burnout syndrome-associated such as socio-demographic
      characteristics, work load, social and family life, leisure activities, extra
      work activities, physical activities, and work-related health problems. METHOD:
      We conducted a cross-sectional, quantitative, prospective epidemiological study
      with 188 surgical clinic nurses. We used the Maslach Burnout Inventory (MBI),
      which is a socio-demographic questionnaire and the most widely used instrument to
      assess Burnout syndrome (three basic dimensions: emotional exhaustion,
      despersonalization and professional underachievement). The socio-demographic
      profile questionnaire wascomposed of questions regarding identification,
      training, time at work, work characteristics and personal circumstances. RESULTS:
      The prevalence of Burnout syndrome was higher (10.1%) and 55, 4% of subjects had
      a propensity to develop this syndrome. The analysis of the socio-demographic
      profile of the nurse sample studied showed that most nurses were childless
      married women, over 35 years of age, working the day shift for 36 hours weekly on
      average, with 2-6 years of post-graduation experience, and without extra
      employments. Factors such as marital status, work load, emotion and work related
      stress aggravated the onset of the syndrome. CONCLUSION: The prevalence and
      propensity of Burnout syndrome were high. Some factors identified can be useful
      for the adoption of preventive actions in order to decrease the prevalence of the
      clinical nurses Burnout syndrome.

PMID- 24860619
TI  - Constitutional chromosomal events at 22q11 and 15q26 in a child with a pilocytic
      astrocytoma of the spinal cord.
AB  - We report on a 9-years-old patient with mild intellectual disability, facial
      dimorphisms, bilateral semicircular canal dysplasia, periventricular nodular
      heterotopias, bilateral hippocampal malrotation and abnormal cerebellar
      foliation, who developed mild motor impairment and gait disorder due to a
      pilocytic astrocytoma of the spinal cord. Array-CGH analysis revealed two
      paternal inherited chromosomal events: a 484.3 Kb duplication on chromosome
      15q26.3 and a 247 Kb deletion on 22q11.23. Further, a second de novo 1.5 Mb
      deletion on 22q11.21 occurred. Chromosome 22 at q11.2 and chromosome 15 at q24q26
      are considered unstable regions subjected to copy number variations, i.e.
      structural alterations of genome, mediated by low copy repeat sequences or
      segmental duplications. The link between some structural CNVs, which compromise
      fundamental processes controlling DNA stability, and genomic disorders suggest a
      plausible scenario for cancer predisposition. Evaluation of the genes at the
      breakpoints cannot account simultaneously for the phenotype and tumour
      development in this patient. The two paternal inherited CNVs arguably are not
      pathogenic and do not contribute to the clinical manifestations. Similarly,
      although the de novo large deletion at 22q11.21 overlaps with the Di George (DGS)
      critical region and results in haploinsufficiency of genes compromising critical
      processes for DNA stability, this case lacks several hallmarks of DGS. 

PMID- 24860620
TI  - Comparison of phenotypic methods for the detection of carbapenem non-susceptible
      Enterobacteriaceae.
AB  - BACKGROUND: Multidrug resistance and, in particular, carbapenem resistance is
      spreading worldwide at an alarming rate, comprehending a variety of bacterial
      species and causing both nosocomial and community acquired outbursts. Early and
      efficient detection of infected patients or colonized carriers are mandatory
      steps in infection control and prevention of multidrug resistance diffusion. The
      latest EUCAST guidelines for detection of carbapenemase-producing
      Enterobacteriaceae have set low clinical breakpoints to ensure the maximum
      detection sensitivity of positive samples. Current workflows involve an initial
      screening step for species and resistance pattern detection, followed by
      phenotypic and/or genotypic confirmation. The aim of the present study was to
      assess the efficiency of six widely used and validated phenotypic assays for the
      detection of carbapenemases/AmpC in Enterobacteriaceae, to estimate the best
      workflow in the routine characterization of Enterobacteriaceae isolates. METHODS:
      A panel of 108 non-repetitive Enterobacteriaceae isolates with reduced
      susceptibility to carbapenems was analyzed by means of 1) Modified Hodge Test, 2)
      Metallo Beta Lactamase Etest, 3) Double disk test with EDTA, 4) Rosco Diagnostica
      KPC and MBL confirm kit (RDCKTM), 5) AmpC Etest and 6) Cloxacillin inhibition
      test. Confirmation and validation of results was achieved by genotypic analysis.
      RESULTS: The most accurate identification of resistance determinants was obtained
      with the combined disc test (Rosco Diagnostica KPC and MBL confirm kit) which had
      to be coupled with the cloxacillin inhibition test for correct detection of AmpC
      enzymes. However, in general, phenotypic tests failed to characterize isolates
      harboring multiple carbapenem resistance determinants, which were successfully
      assessed only by PCR-based analysis. CONCLUSIONS: To detect and control the
      spread of pathogens with complicated resistance patterns, both optimized
      phenotypic analysis (i.e. Rosco Diagnostica KPC and MBL confirm kit coupled with
      the cloxacillin inhibition test) and genotypic assays are recommended in the
      routine diagnostic of clinical laboratories.

PMID- 24860622
TI  - Effect of single tablet of fixed-dose amlodipine and atorvastatin on blood
      pressure/lipid control, oxidative stress, and medication adherence in type 2
      diabetic patients.
AB  - BACKGROUND: Oxidized low-density lipoprotein (LDL) plays central roles in the
      formation and progression of atherosclerotic lesions. Malondialdehyde (MDA)
      modified LDL (MDA-LDL) is speculated to be generated as a result of oxidative
      stress in the human body. Because both amlodipine and atorvastatin have been
      reported to reduce oxidative stress, it is expected that both drugs would have a
      favorable influence to reduce oxidative stress. OBJECTIVE: The objective of this
      study was to investigate the effects of a single pill of amlodipine (5
      mg)/atorvastatin (10 mg) on oxidative stress, blood pressure/lipid control and
      adherence to medication in patients with type 2 diabetes. METHODS: This
      combination tablet was administered to 29 patients (16 male), and MDA-LDL, blood
      pressure, lipid profile, renal/liver function, CPK, hs-CRP, adiponectin, BNP, and
      HbA1c were measured at baseline, 6, and 12 months, and baPWV and mean IMT were
      measured at baseline and 12 months. Medication adherence was examined using a
      questionnaire at 6 months. RESULTS: MDA-LDL was decreased significantly. LDL-C,
      TG, and Cr were significantly decreased at 6 and 12 months compared with
      baseline. eGFR was increased at 6 months, and urinary albumin/creatinine ratio
      was decreased at 12 months. BNP was decreased at 6 and 12 months, and adiponectin
      was increased at 12 months. Both mean IMT and baPWV were significantly decreased.
      The results of the questionnaire showed that 93% of patients were satisfied with
      this medication. No severe adverse event was observed. CONCLUSION: This
      combination tablet controlled both hypertension and dyslipidemia well in type 2
      diabetic patients. The deceases in mean IMT and baPWV might suggest the
      improvement of atherosclerosis by this medication, which could be caused by the
      reduction of oxidative stress measured by MDA-LDL. In addition, this medication
      is expected to improve medication adherence.

PMID- 24860621
TI  - Systemic lupus erythematosus diagnostics in the 'omics' era.
AB  - Systemic lupus erythematosus is a complex autoimmune disease affecting multiple
      organ systems. Currently, diagnosis relies upon meeting at least four out of
      eleven criteria outlined by the ACR. The scientific community actively pursues
      discovery of novel diagnostics in the hope of better identifying susceptible
      individuals in early stages of disease. Comprehensive studies have been conducted
      at multiple biological levels including: DNA (or genomics), mRNA (or
      transcriptomics), protein (or proteomics) and metabolites (or metabolomics). The
      'omics' platforms allow us to re-examine systemic lupus erythematosus at a
      greater degree of molecular resolution. More importantly, one is hopeful that
      these 'omics' platforms may yield newer biomarkers for systemic lupus
      erythematosus that can help clinicians track the disease course with greater
      sensitivity and specificity.

PMID- 24860623
TI  - FEASIBILITY STUDY OF A CLINICAL BLOOD-BRAIN BARRIER OPENING ULTRASOUND SYSTEM.
AB  - In this paper, we investigate the focalization properties of single-element
      transducers at intermediate frequencies (500 kHz) through primate and human
      skulls. The study addresses the transcranial targeting involved in ultrasound
      induced blood brain barrier (BBB) opening with clinically relevant targets such
      as the hippocampus and the basal ganglia, which are typically affected by early
      Alzheimer's and Parkinson's disease, respectively. The targeted brain structures
      were extracted from three-dimensional (3D) brain atlases registered with the
      skulls and used to virtually position and orient the transducers. The frequency
      dependence is first investigated and the capability of targeting of different
      structures is explored. Preliminary in vivo feasibility is investigated in mice
      at this frequency. A simple, affordable and convenient system is found to be
      feasible for BBB opening in primates and humans capable of successfully targeting
      the hippocampus, putamen and substantia nigra and could thus allow for its
      broader impact and applications.

PMID- 24860624
TI  - A Smartphone App to Screen for HIV-Related Neurocognitive Impairment.
AB  - BACKGROUND: Neurocognitive Impairment (NCI) is one of the most common
      complications of HIV-infection, and has serious medical and functional
      consequences. However, screening for it is not routine and NCI often goes
      undiagnosed. Screening for NCI in HIV disease faces numerous challenges, such as
      limited screening tests, the need for specialized equipment and apparatuses, and
      highly trained personnel to administer, score and interpret screening tests. To
      address these challenges, we developed a novel smartphone-based screening tool,
      NeuroScreen, to detect HIV-related NCI that includes an easy-to-use graphical
      user interface with ten highly automated neuropsychological tests. AIMS: To
      examine NeuroScreen's: 1) acceptability among patients and different potential
      users; 2) test construct and criterion validity; and 3) sensitivity and
      specificity to detect NCI. METHODS: Fifty HIV+ individuals were administered a
      gold-standard neuropsychological test battery, designed to detect HIV-related
      NCI, and NeuroScreen. HIV+ test participants and eight potential provider-users
      of NeuroScreen were asked about its acceptability. RESULTS: There was a high
      level of acceptability of NeuroScreen by patients and potential provider-users.
      Moderate to high correlations between individual NeuroScreen tests and paper-and
      pencil tests assessing the same cognitive domains were observed. NeuroScreen also
      demonstrated high sensitivity to detect NCI. CONCLUSION: NeuroScreen, a highly
      automated, easy-to-use smartphone-based screening test to detect NCI among HIV
      patients and usable by a range of healthcare personnel could help make routine
      screening for HIV-related NCI feasible. While NeuroScreen demonstrated robust
      psychometric properties and acceptability, further testing with larger and less
      neurocognitively impaired samples is warranted.

PMID- 24860625
TI  - Completely intracorporeal robotic-assisted laparoscopic ileovesicostomy: initial
      results.
AB  - We present a series of robotic-assisted laparoscopic ileovesicostomies with bowel
      work performed completely intracorporeally. The four patients selected for this
      procedure were all diagnosed with neurogenic bladder and failed conservative
      medical therapy. Preoperative patient data included age, body mass index (BMI),
      and urodynamic (UD) study results. Intra-operative data included estimated blood
      loss (EBL), operative time, and intra-operative complications. Post-operative
      data included return to bowel function, post-operative complications, and length
      of hospital stay (LOS). All bowel work was completed intracorporeally with the
      exception of stoma maturation. Four robotic ileovesicostomies were performed. Pre
      operative urodynamic study results showed either elevated detrusor pressures or
      limited bladder capacities in addition to the inability to perform self
      catheterization. The mean patient age was 40 years and mean BMI was 26 kg/m(2).
      Average EBL and operative time were 131 ml and 290 min, respectively. No intra
      operative complications occurred. Bowel function, as defined as flatus, returned
      on average 3.8 days after surgery and average LOS, defined as discharge home or
      discharge to the spinal cord unit, was 7.5 days. Mean follow-up time was 25.8
      months. Post-operative urodynamic studies revealed low stomal leak point pressure
      (<10 cmH2O). This study is the first to describe a completely intracorporeally
      robotic-assisted laparoscopic ileovesicostomy with safe and effective outcomes
      after more than 2 years of follow-up. 

PMID- 24860627
TI  - A case of osteochondritis dissecans of the lateral femoral condyle and
      patellofemoral joint surface occurring in the same knee.

PMID- 24860626
TI  - Evaluating the effect of emergency department crowding on triage destination.
AB  - BACKGROUND: Emergency Department (ED) crowding has been studied for the last 20
      years, yet many questions remain about its impact on patient care. In this study,
      we aimed to determine if ED crowding influenced patient triage destination and
      intensity of investigation, as well as rates of unscheduled returns to the ED. We
      focused on patients presenting with chest pain or shortness of breath, triaged as
      high acuity, and who were subsequently discharged home. METHODS: This pilot study
      was a health records review of 500 patients presenting to two urban tertiary care
      EDs with chest pain or shortness of breath, triaged as high acuity and
      subsequently discharged home. Data extracted included triage time, date,
      treatment area, time to physician initial assessment, investigations ordered,
      disposition, and return ED visits within 14 days. We defined ED crowding as ED
      occupancy greater than 1.5. Data were analyzed using descriptive statistics and
      the chi(2) and Fisher exact tests. RESULTS: Over half of the patients, 260/500
      (52.0%) presented during conditions of ED crowding. More patients were triaged to
      the non-monitored area of the ED during ED crowding (65/260 (25.0%) vs. 39/240
      (16.3%) when not crowded, P = 0.02). During ED crowding, mean time to physician
      initial assessment was 132.0 minutes in the non-monitored area vs. 99.1 minutes
      in the monitored area, P <0.0001. When the ED was not crowded, mean time to
      physician initial assessment was 122.3 minutes in the non-monitored area vs. 67
      minutes in the monitored area, P = 0.0003. Patients did not return to the ED more
      often when triaged during ED crowding: 24/260 (9.3%) vs. 29/240 (12.1%) when ED
      was not crowded (P = 0.31). Overall, when triaged to the non-monitored area of
      the ED, 44/396 (11.1%) patients returned, whereas in the monitored area 9/104
      (8.7%) patients returned, P = 0.46. CONCLUSIONS: ED crowding conditions appeared
      to influence triage destination in our ED leading to longer wait times for high
      acuity patients. This did not appear to lead to higher rates of return ED visits
      amongst discharged patients in this cohort. Further research is needed to
      determine whether these delays lead to adverse patient outcomes.

PMID- 24860628
TI  - Rare case of exogenous Candida dubliniensis endophthalmitis: a case report and
      brief review of the literature.
AB  - BACKGROUND: Candida dubliniensis is a recently described opportunistic fungal
      pathogen that rarely infects the eye. Reported cases of C. dubliniensis
      endophthalmitis have been of endogenous etiology and demonstrated recovery of
      visual acuity with timely treatment. We herein report an unusual case of severe
      C. dubliniensis endophthalmitis requiring enucleation. FINDINGS: This is a
      retrospective, descriptive case report with a brief literature review. A 41-year
      old Caucasian man, with a history of blunt trauma 8 months prior, presented to
      the emergency department with left eye pain and loss of vision 2 days after
      complicated cataract surgery. He was first evaluated by an outside
      ophthalmologist 3 months after trauma for left eye pain and progressive vision
      loss. He was found to have light perception vision with non-granulomatous
      anterior uveitis but no sign of ruptured globe. A dense cataract developed while
      he was treated with topical and subtenon's corticosteroids for which he underwent
      cataract surgery. Our examination revealed no light perception vision with a
      relative afferent pupillary defect, elevated intraocular pressure, moderate
      anterior chamber reaction, pupillary membrane, vitritis, and choroidal thickening
      on B-scan ultrasonography. Diagnostic vitrectomy revealed purulent vitreal
      debris, retinal detachment with severe retinal necrosis, and choroidal
      infiltrates. Operative fungal cultures grew C. dubliniensis. Despite intravitreal
      and systemic anti-fungal treatment, vision and pain did not improve, resulting in
      subsequent enucleation. CONCLUSION: C. dubliniensis endophthalmitis is uncommonly
      encountered and typically has reasonable visual outcomes. This is the first
      reported case of C. dubliniensis, likely exogenous endophthalmitis, resulting in
      enucleation, illustrating the potential virulence of this newly described
      organism.

PMID- 24860629
TI  - Study of a Functional Polymorphism in the PER3 Gene and Diurnal Preference in a
      Colombian Sample.
AB  - Polymorphisms in human clock genes have been evaluated as potential factors
      influencing circadian phenotypes in several populations. There are conflicting
      results for the association of a VNTR in the PER3 gene and diurnal preference in
      different studies. The objective of this study was to investigate the association
      between diurnal preference and daytime somnolence with the PER3 VNTR polymorphism
      (rs57875989) in healthy subjects from Colombia, a Latin American population.A
      total of 294 undergraduate university students from Bogota, Colombia participated
      in this study. Two validated self-report questionnaires, the Composite Scale of
      Morningness (CSM) and the Epworth Sleep Scale (ESS) were used to assess diurnal
      preference and daytime somnolence, respectively. Individuals were genotyped for
      the PER3 VNTR using conventional PCR. Statistical comparisons were carried out
      with PLINK and SNPStats programs. The PER3 VNTR polymorphism was not associated
      with either diurnal preference or daytime somnolence in this population. No
      significant differences in mean scores for those scales were found between PER3
      VNTR genotypes. In addition, there were no differences in allelic or genotypic
      frequencies between chronotype categories. This is consistent with several
      negative findings in other populations, indicating that the proposed influence of
      this polymorphism in diurnal preference, and related endophenotypes of
      neuropsychiatric importance, needs further clarification. This is the first
      report of molecular genetics of human circadian phenotypes in a Spanish-speaking
      population. 

PMID- 24860630
TI  - Ultrasound as a feasible method for the assessment of malrotation.
AB  - BACKGROUND: In malrotation the position of third portion of duodenum (D3) is
      always intramesenteric. Demonstration of normal retromesenteric-retroperitoneal
      position of D3 on ultrasound (US) can rule out malrotation. The aim of this study
      was to evaluate the feasibility of US in demonstrating the retroperitoneal D3.
      MATERIAL/METHODS: Abdominal US study was done for various indications in 60
      newborns and infants (mean age: 33 days [range: 4-100 days]; 56.7% male) by an
      expert pediatric radiologist. The position of D3 and its adjacent structures was
      evaluated in axial and longitudinal planes by linear and curved transducers.
      RESULTS: A normal retromesenteric-retroperitoneal D3 located between the superior
      mesenteric artery and the aorta was seen on US in all patients, including those
      with extensive gas in the bowel. The mean time of D3 observation was 47.8 s (10
      180 s). Ultrasound was also capable of demonstrating D3 structure, diameter,
      content, adjacent structures, relative position of the superior mesenteric artery
      and vein. CONCLUSIONS: Ultrasound is a simple, fast and highly accurate tool to
      confirm the retroperitoneal position of D3. Ultrasound can be used as a screening
      method for malrotation eliminating the need for unnecessary barium studies.

PMID- 24860631
TI  - What's new in renal cell cancer research? Highlights of GU-ASCO 2014.
AB  - One of the major areas of research presented at the 2014 Genitourinary Cancers
      Symposium (GU-ASCO 2014) pertained to the management of renal cell cancer (RCC).
      The following pages provide a summary of some of the most important presentations
      and posters presented during the 3-day symposium. 

PMID- 24860632
TI  - Canadian content at GU-ASCO 2014: Highlights of research involving Canadian
      researchers.
AB  - The 2014 Genitourinary Cancers Symposium (GU-ASCO 2014) provided an opportunity
      for researchers from around the world to present their research in a variety of
      fields, including prostate, renal cell, penile, urethral and testicular cancers.
      Over the symposium's 3 days, Canadian researchers were well-represented, with a
      number of oral abstract podium presentations and many more research posters. The
      following section provides brief summaries of some of the most interesting work
      involving Canadians presented at GU-ASCO 2014 and a listing of all the studies
      that included contributions from Canadian researchers. 

PMID- 24860633
TI  - Presenters.

PMID- 24860634
TI  - New paradigms in the treatment of genitourinary malignancies: GU-ASCO Update
      2014.

PMID- 24860635
TI  - What's new in prostate cancer research? Highlights of GU-ASCO 2014.
AB  - At the 2014 Genitourinary Cancers Symposium (GU-ASCO 2014), international
      researchers presented an extensive array of research in the field of prostate
      cancer treatment. The following pages provide a summary of some of the most
      compelling results presented during the 3-day symposium. 

PMID- 24860639
TI  - Psychological Stress and Induced Ischemic Syndromes.

PMID- 24860637
TI  - Insight into the Mechanism of Graphene Oxide Degradation via the Photo-Fenton
      Reaction.
AB  - Graphene represents an attractive two-dimensional carbon-based nanomaterial that
      holds great promise for applications such as electronics, batteries, sensors, and
      composite materials. Recent work has demonstrated that carbon-based nanomaterials
      are degradable/biodegradable, but little work has been expended to identify
      products formed during the degradation process. As these products may have
      toxicological implications that could leach into the environment or the human
      body, insight into the mechanism and structural elucidation remain important as
      carbon-based nanomaterials become commercialized. We provide insight into a
      potential mechanism of graphene oxide degradation via the photo-Fenton reaction.
      We have determined that after 1 day of treatment intermediate oxidation products
      (with MW 150-1000 Da) were generated. Upon longer reaction times (i.e., days 2
      and 3), these products were no longer present in high abundance, and the system
      was dominated by graphene quantum dots (GQDs). On the basis of FTIR, MS, and NMR
      data, potential structures for these oxidation products, which consist of
      oxidized polycyclic aromatic hydrocarbons, are proposed.

PMID- 24860638
TI  - Update on heart failure with preserved ejection fraction.
AB  - Heart failure with preserved ejection fraction (HFPEF) is the most common form of
      heart failure (HF) in older adults, and is increasing in prevalence as the
      population ages. Morbidity and long-term mortality in HFPEF are substantial and
      can be similar to HF with reduced ejection fraction (HFREF), yet HFPEF therapy
      remains empirical and treatment guidelines are based primarily on expert
      consensus. Neurohormonal blockade has revolutionized the management of HFREF, but
      trials in HFPEF based on this strategy have been disappointing to date. However,
      many recent studies have increased knowledge about HFPEF. The concept of HFPEF
      has evolved from a 'cardio-centric' model to a syndrome that may involve multiple
      cardiovascular and non-cardiovascular mechanisms. Emerging data highlight the
      importance of non-pharmacological management strategies and assessment of non
      cardiovascular comorbidities. Animal models, epidemiological cohorts, and small
      human studies suggest that oxidative stress and inflammation contribute to HFPEF,
      potentially leading to development of new therapeutic targets.

PMID- 24860636
TI  - MarA, SoxS and Rob of Escherichia coli - Global regulators of multidrug
      resistance, virulence and stress response.
AB  - Bacteria have a great capacity for adjusting their metabolism in response to
      environmental changes by linking extracellular stimuli to the regulation of genes
      by transcription factors. By working in a co-operative manner, transcription
      factors provide a rapid response to external threats, allowing the bacteria to
      survive. This review will focus on transcription factors MarA, SoxS and Rob in
      Escherichia coli, three members of the AraC family of proteins. These homologous
      proteins exemplify the ability to respond to multiple threats such as oxidative
      stress, drugs and toxic compounds, acidic pH, and host antimicrobial peptides.
      MarA, SoxS and Rob recognize similar DNA sequences in the promoter region of more
      than 40 regulatory target genes. As their regulons overlap, a finely tuned
      adaptive response allows E. coli to survive in the presence of different assaults
      in a co-ordinated manner. These regulators are well conserved amongst
      Enterobacteriaceae and due to their broad involvement in bacterial adaptation in
      the host, have recently been explored as targets to develop new anti-virulence
      agents. The regulators are also being examined for their roles in novel
      technologies such as biofuel production.

PMID- 24860640
TI  - How Does Religiosity Enhance Well-Being? The Role of Perceived Control.
AB  - Religiousness and spirituality (R/S) are consistently linked with positive
      indicators of well-being, but the mechanisms behind these associations remain
      largely unknown. We hypothesize that an individual's level of perceived control
      (PC) acts as a mediator of this relationship and that this effect is stronger in
      older adults. Participants were 529 adults from the Notre Dame Study of Health
      and Well-Being (aged 31-88). Regression analyses tested both mediating and
      moderating functions of PC for three different R/S components (religious
      practices, daily spiritual experiences, and religious/spiritual coping);
      composite variables were used for PC and subjective well-being (SWB) in all
      analyses. These effects were tested using the full sample, as well as separately
      by age group (early midlife, aged 31-49; late midlife, aged 50-59; and later
      life, aged 60 and over), in order to discover any age differences that may exist.
      Results revealed differences by both R/S dimension and age group: PC partially
      mediated the religious practices-SWB relationship in the full sample and in the
      later life group; the effects of religious/spiritual coping and spiritual
      experiences on SWB were partially mediated by PC in the full sample, the late
      midlife group, and the later life group; and none of the R/S-SWB relationships
      were mediated in the early midlife group. Moderating effects were indicated by
      significant interactions between PC and spiritual experiences in the full sample,
      PC and religious coping in the full sample, and PC and religious practices in the
      later life group.

PMID- 24860641
TI  - PTSD as Meaning Violation: Testing a Cognitive Worldview Perspective.
AB  - The cognitive perspective on post-traumatic stress disorder (PTSD) has been
      successful in explaining many PTSD-related phenomena and in developing effective
      treatments, yet some of its basic assumptions remain surprisingly under-examined.
      The present study tested two of these assumptions: (1) situational appraisals of
      the event as violating global meaning (i.e., beliefs and goals) is related to
      PTSD symptomatology, and (2) the effect of situational appraisals of violation on
      PTSD symptomatology is mediated by global meaning (i.e., views of self and
      world). We tested these assumptions in a cross-sectional study of 130 college
      students who had experienced a DSM-IV level trauma. Structural equation modeling
      showed that appraisals of the extent to which the trauma violated one's beliefs
      and goals related fairly strongly to PTSD. In addition, the effects of appraisals
      of belief and goal violations on PTSD symptoms were fully mediated through
      negative global beliefs about both the self and the world. These findings support
      the cognitive worldview perspective, highlighting the importance of the meaning
      individuals assign to traumatic events, particularly the role of meaning
      violation.

PMID- 24860642
TI  - Importance of Breast Cancer Subtype in the Development of Androgen Receptor
      Directed Therapy.
AB  - The androgen receptor (AR) has re-emerged as a potential therapeutic target in
      breast cancer. This stems from recent progress made in preclinical models, that
      have recognized important differences in the effect of AR expression on patient
      outcomes among different breast cancer subtypes. In parallel, the clinical
      development of new generations of AR directed therapies for prostate cancer has
      begun to mature. The availability of these new agents has translated into new
      trials to treat breast cancer. It is critical that studies of the effect of AR
      expression and signaling in breast cancer be context and subtype specific in
      order to successfully target AR signalling as a therapeutic strategy for breast
      cancer. We will review developments in preclinical studies, and recent clinical
      trials targeting AR in breast cancer.

PMID- 24860644
TI  - HeatMapViewer: interactive display of 2D data in biology.
AB  - SUMMARY: The HeatMapViewer is a BioJS component that lays-out and renders two
      dimensional (2D) plots or heat maps that are ideally suited to visualize matrix
      formatted data in biology such as for the display of microarray experiments or
      the outcome of mutational studies and the study of SNP-like sequence variants. It
      can be easily integrated into documents and provides a powerful, interactive way
      to visualize heat maps in web applications. The software uses a scalable graphics
      technology that adapts the visualization component to any required resolution, a
      useful feature for a presentation with many different data-points. The component
      can be applied to present various biological data types. Here, we present two
      such cases - showing gene expression data and visualizing mutability landscape
      analysis. AVAILABILITY: https://github.com/biojs/biojs;
      http://dx.doi.org/10.5281/zenodo.7706.

PMID- 24860645
TI  - Recommendations to enable drug development for inherited neuropathies: Charcot
      Marie-Tooth and Giant Axonal Neuropathy.
AB  - Approximately 1 in 2500 Americans suffer from Charcot-Marie-Tooth (CMT) disease.
      The underlying disease mechanisms are unique in most forms of CMT, with many
      point mutations on various genes causing a toxic accumulation of misfolded
      proteins. Symptoms of the disease often present within the first two decades of
      life, with CMT1A patients having reduced compound muscle and sensory action
      potentials, slow nerve conduction velocities, sensory loss, progressive distal
      weakness, foot and hand deformities, decreased reflexes, bilateral foot drop and
      about 5% become wheelchair bound. In contrast, the ultra-rare disease Giant
      Axonal Neuropathy (GAN) is frequently described as a recessively inherited
      condition that results in progressive nerve death. GAN usually appears in early
      childhood and progresses slowly as neuronal injury becomes more severe and leads
      to death in the second or third decade. There are currently no treatments for any
      of the forms of CMTs or GAN. We suggest that further clinical studies should
      analyse electrical impedance myography as an outcome measure for CMT. Further,
      additional quality of life (QoL) assessments for these CMTs are required, and we
      need to identify GAN biomarkers as well as develop new genetic testing panels for
      both diseases. We propose that using the Global Registry of Inherited Neuropathy
      (GRIN) could be useful for many of these studies. Patient advocacy groups and
      professional organizations (such as the Hereditary Neuropathy Foundation (HNF),
      Hannah's Hope Fund (HHF), The Neuropathy Association (TNA) and the American
      Association of Neuromuscular and Electrodiagnostic Medicine (AANEM) can play a
      central role in educating clinicians and patients. Undertaking these studies will
      assist in the correct diagnosis of disease recruiting patients for clinical
      studies, and will ultimately improve the endpoints for clinical trials. By
      addressing obstacles that prevent industry investment in various forms of
      inherited neuropathies, we can envision treatment options for these rare diseases
      in the near future. 

PMID- 24860643
TI  - Rare deleterious mutations of the gene EFR3A in autism spectrum disorders.
AB  - BACKGROUND: Whole-exome sequencing studies in autism spectrum disorder (ASD) have
      identified de novo mutations in novel candidate genes, including the synaptic
      gene Eighty-five Requiring 3A (EFR3A). EFR3A is a critical component of a protein
      complex required for the synthesis of the phosphoinositide PtdIns4P, which has a
      variety of functions at the neural synapse. We hypothesized that deleterious
      mutations in EFR3A would be significantly associated with ASD. METHODS: We
      conducted a large case/control association study by deep resequencing and
      analysis of whole-exome data for coding and splice site variants in EFR3A. We
      determined the potential impact of these variants on protein structure and
      function by a variety of conservation measures and analysis of the Saccharomyces
      cerevisiae Efr3 crystal structure. We also analyzed the expression pattern of
      EFR3A in human brain tissue. RESULTS: Rare nonsynonymous mutations in EFR3A were
      more common among cases (16 / 2,196 = 0.73%) than matched controls (12 / 3,389 =
      0.35%) and were statistically more common at conserved nucleotides based on an
      experiment-wide significance threshold (P = 0.0077, permutation test). Crystal
      structure analysis revealed that mutations likely to be deleterious were also
      statistically more common in cases than controls (P = 0.017, Fisher exact test).
      Furthermore, EFR3A is expressed in cortical neurons, including pyramidal neurons,
      during human fetal brain development in a pattern consistent with ASD-related
      genes, and it is strongly co-expressed (P < 2.2 * 10(-16), Wilcoxon test) with a
      module of genes significantly associated with ASD. CONCLUSIONS: Rare deleterious
      mutations in EFR3A were found to be associated with ASD using an experiment-wide
      significance threshold. Synaptic phosphoinositide metabolism has been strongly
      implicated in syndromic forms of ASD. These data for EFR3A strengthen the
      evidence for the involvement of this pathway in idiopathic autism.

PMID- 24860646
TI  - shRNA-seq data analysis with edgeR.
AB  - Pooled short hairpin RNA sequencing (shRNA-seq) screens are becoming increasingly
      popular in functional genomics research, and there is a need to establish optimal
      analysis tools to handle such data. Our open-source shRNA processing pipeline in
      edgeR provides a complete analysis solution for shRNA-seq screen data, that
      begins with the raw sequence reads and ends with a ranked lists of candidate
      shRNAs for downstream biological validation. We first summarize the raw data
      contained in a fastq file into a matrix of counts (samples in the columns,
      hairpins in the rows) with options for allowing mismatches and small shifts in
      hairpin position. Diagnostic plots, normalization and differential representation
      analysis can then be performed using established methods to prioritize results in
      a statistically rigorous way, with the choice of either the classic exact testing
      methodology or a generalized linear modelling that can handle complex
      experimental designs. A detailed users' guide that demonstrates how to analyze
      screen data in edgeR along with a point-and-click implementation of this workflow
      in Galaxy are also provided. The edgeR package is freely available from
      http://www.bioconductor.org. 

PMID- 24860649
TI  - Surface-associated microbes continue to surprise us in their sophisticated
      strategies for assembling biofilm communities.
AB  - Microorganisms are rarely found in isolation. Frequently, they live as complex
      consortia or communities known as biofilms. The microbes within these complex
      structures are typically enmeshed in a matrix of macromolecules collectively
      known as the extracellular polymeric substances (EPS). The last decade has seen
      enormous growth in the breadth and depth of biofilm-related research. An
      important area of focus has been the study of pure culture biofilms of different
      model species. This work has informed us about the different genetic determinants
      involved in biofilm formation and the environmental conditions that influence the
      process. These studies have also highlighted both species-specific aspects of
      biofilm development and common trends observed across many different organisms.
      This report highlights some exciting findings in recent biofilm-related research.

PMID- 24860651
TI  - Advances in the management of macular degeneration.
AB  - Current management of age-related macular degeneration (AMD) can be divided into
      two categories: first, anti-vasoendothelial growth factor (anti-VEGF) injection
      for wet macular degeneration; second, anti-oxidant vitamins for dry macular
      degeneration. New therapies are being developed for both of these diseases using
      novel technologies and different modes of administration. The hope is that some
      of these therapies will achieve significant improvement to current management and
      prevent future loss of vision in this devastating eye condition. 

PMID- 24860652
TI  - Novel approaches in treatment of pediatric anxiety.
AB  - Pediatric anxiety disorders have high prevalence rates and morbidity and are
      associated with considerable functional impairment and distress. They may be
      predictors for the development of other psychiatric disorders and, without
      intervention, are more likely to persist into adulthood. While evidence-based
      pharmacological and behavioral interventions are currently available, there
      remains a sizable subset of youth who remain only partially treatment-responsive
      and therefore symptomatic following treatment. Novel methods of treatment,
      pharmacologic and non-pharmacologic, including acceptance and commitment therapy
      (ACT), attention bias modification (ABM), d-cycloserine (DCS) augmentation of
      cognitive behavioral treatment (CBT), and glutamatergic agents such as riluzole,
      are briefly introduced and discussed. 

PMID- 24860654
TI  - Management of pemphigus.
AB  - Pemphigus is an autoimmune blistering disease characterized by cutaneous and
      mucosal blisters and erosions. Though systemic corticosteroids have been the
      mainstay of treatment for pemphigus over the years, more recently research has
      focused on steroid-sparing agents. This review looks at the commonly used steroid
      sparing agents in pemphigus and the evidence from randomized controlled trials
      (RCTs) supporting their use. 

PMID- 24860650
TI  - Cell-mediated immunity to human CMV infection: a brief overview.
AB  - The cellular immune response to human cytomegalovirus (HCMV) has different
      components originating from both the adaptive and innate immune systems. There is
      a significant global interest in understanding how the immune system keeps HCMV
      under control, in particular with a view to situations where HCMV infection
      causes severe damage. Such settings include HIV infection, transplantation, and
      maybe most importantly perinatal medicine, HCMV being a major cause of sometimes
      catastrophic birth defects. The development of an active HCMV vaccine has proven
      very difficult but some recent successes raise hope that this might be available
      in the future. However, adoptive transfer of HCMV-specific T cells has been
      successfully used to prevent CMV disease after bone marrow transplantation for
      many years. In fact, the CD8 T cell response has been thought to be the most
      important effector response, with numerous reports focusing on specific T cell
      subsets recognizing select peptides in select human leukocyte antigen (HLA)
      contexts. However, it is becoming increasingly clear now that other cells, first
      and foremost CD4 T cells, but also gamma/delta (gamma/delta) T cells and natural
      killer cells, are critically involved in the cellular immune response to HCMV.
      This commentary aims to provide a brief overview of the field. 

PMID- 24860647
TI  - Mitochondrial oxidative stress in aging and healthspan.
AB  - The free radical theory of aging proposes that reactive oxygen species (ROS)
      induced accumulation of damage to cellular macromolecules is a primary driving
      force of aging and a major determinant of lifespan. Although this theory is one
      of the most popular explanations for the cause of aging, several experimental
      rodent models of antioxidant manipulation have failed to affect lifespan.
      Moreover, antioxidant supplementation clinical trials have been largely
      disappointing. The mitochondrial theory of aging specifies more particularly that
      mitochondria are both the primary sources of ROS and the primary targets of ROS
      damage. In addition to effects on lifespan and aging, mitochondrial ROS have been
      shown to play a central role in healthspan of many vital organ systems. In this
      article we review the evidence supporting the role of mitochondrial oxidative
      stress, mitochondrial damage and dysfunction in aging and healthspan, including
      cardiac aging, age-dependent cardiovascular diseases, skeletal muscle aging,
      neurodegenerative diseases, insulin resistance and diabetes as well as age
      related cancers. The crosstalk of mitochondrial ROS, redox, and other cellular
      signaling is briefly presented. Potential therapeutic strategies to improve
      mitochondrial function in aging and healthspan are reviewed, with a focus on
      mitochondrial protective drugs, such as the mitochondrial antioxidants MitoQ,
      SkQ1, and the mitochondrial protective peptide SS-31. 

PMID- 24860653
TI  - Advances in the treatment of rheumatoid arthritis.
AB  - The intense pursuit of novel therapies in rheumatoid arthritis has provided
      physicians with an assorted set of biologic drugs to treat patients with moderate
      to severe disease activity. Nine different biologic therapies are currently
      available: seven inhibitors of pro-inflammatory cytokines (five targeting tumor
      necrosis factor [TNF], one interleukin [IL]-1 and one IL-6), as well as a T- and
      a B-lymphocyte targeting agent. All these drugs have roughly similar efficacy
      profiles and are approved as first- or second-line therapy in patients who failed
      to respond to conventional disease-modifying anti-rheumatic drugs (DMARDs) and in
      most cases for first line use in rheumatoid arthritis as well. Despite the
      irrefutable clinical and radiological benefits of biologic therapies, there are
      still low rates of patients achieving stable remission. Therefore, the quest for
      new and more effective biologic therapies continues and every year new drugs are
      tested. Simultaneously, optimal use of established agents is being studied in
      different ways. Recently, the approval of the first small molecule targeting
      intracellular pathways has opened a new chapter in the treatment of rheumatoid
      arthritis. Other emerging treatment strategies include the activation of
      regulatory T cells as well as new cytokine-targeting therapies. 

PMID- 24860655
TI  - Geriatric considerations in the treatment of advanced prostate cancer.
AB  - Prostate cancer is the most common non-cutaneous cancer in US men and mainly
      affects elderly patients, with most new diagnoses occurring in those over 65. As
      the geriatric population in the US continues to grow, the incidence of this
      disease is likewise expected to rise. Many older patients are diagnosed with
      advanced disease or are treated only when their disease becomes symptomatic or
      metastatic. The treatment options for advanced prostate cancer have increased
      dramatically in the last decade. It is important to understand the nuances of
      caring for an elderly cancer patient in order to optimally treat prostate cancer,
      such as the importance of using a geriatric assessment to uncover overlooked or
      under-reported vulnerabilities. In addition, many of the newly approved agents
      for the treatment of advanced prostate cancer have a unique mechanism of action
      and toxicities that warrant consideration when choosing therapies for older
      patients. This review focuses on the importance of a geriatric assessment as well
      as the considerations of treating elderly patients with the newer agents approved
      for prostate cancer. 

PMID- 24860656
TI  - Point of care cutaneous imaging technology in melanoma screening and mole
      mapping.
AB  - Melanoma is a malignancy of melanocytes or pigment-producing cells located
      predominantly in the skin. It is less common than other skin cancers but causes
      the greatest number of skin cancer-related deaths worldwide. The incidence of
      melanoma continues to increase and early detection is the most promising means of
      decreasing morbidity and mortality. Currently, physicians perform routine skin
      cancer screenings for melanoma without the benefit of imaging devices more
      advanced than handheld magnifiers or dermatoscopes. However, it is possible that
      the diagnosis of melanoma may be improved with technology that provides
      diagnostic discrimination beyond what is possible on routine inspection. This
      article reviews current and emerging technologies to aid in the diagnosis of
      melanoma. Ultimately, these advances may enhance the early diagnosis of melanoma.

PMID- 24860659
TI  - Thixotropic behaviour of thickened sewage sludge.
AB  - The aim of the work is a description of the rheological behaviour of thickened
      sewage sludge. The sample of thickened sludge was collected from the wastewater
      treatment plant, where pressure flotation unit is used for a process of
      thickening. The value of dry matter of collected sample was 3.52%. Subsequently
      the sample was diluted and the rheological properties of individual samples were
      obtained. Several types of rheological tests were used for the determination of
      the sample. At first the hysteresis loop test was performed. The next test was
      focused on the time-dependency, i.e. measurement of dependence of dynamic
      viscosity on the time at constant shear rate. Further dependence dynamic
      viscosity on the temperature was performed. Then the activation energy was
      obtained from measured values. Finally, the hysteresis areas were counted and
      measured values were evaluated with use of Herschel-Bulkley mathematical model. 

PMID- 24860658
TI  - Improvements in current treatments and emerging therapies for adult obstructive
      sleep apnea.
AB  - Obstructive sleep apnea (OSA) is common and is associated with a number of
      adverse outcomes, including an increased risk for cardiovascular disease. Typical
      treatment approaches, including positive airway pressure, oral appliances,
      various upper airway surgeries, and/or weight loss, can improve symptoms and
      reduce the severity of disease in select patient groups. However, these
      approaches have several potential limitations, including suboptimal adherence,
      lack of suitability for all patient groups, and/or absence of adequate outcomes
      data. Emerging potential therapeutic options, including nasal expiratory positive
      airway pressure (PAP), oral negative pressure, upper airway muscle stimulation,
      and bariatric surgery, as well as improvements in existing treatments and the
      utilization of improving technologies are moving the field forward and should
      offer effective therapies to a wider group of patients with OSA. 

PMID- 24860657
TI  - Advances in understanding and treating dystrophic epidermolysis bullosa.
AB  - Epidermolysis bullosa is a group of inherited disorders that can be both systemic
      and life-threatening. Standard treatments for the most severe forms of this
      disorder, typically limited to palliative care, are ineffective in reducing the
      morbidity and mortality due to complications of the disease. Emerging therapies
      such as the use of allogeneic cellular therapy, gene therapy, and protein therapy
      have all shown promise, but it is likely that several approaches will need to be
      combined to realize a cure. For recessive dystrophic epidermolysis bullosa, each
      particular therapeutic approach has added to our understanding of type VII
      collagen (C7) function and the basic biology surrounding the disease. The
      efficacy of these therapies and the mechanisms by which they function also give
      us insight into developing future strategies for treating this and other
      extracellular matrix disorders. 

PMID- 24860660
TI  - Removal of Arsenic (III, V) from aqueous solution by nanoscale zero-valent iron
      stabilized with starch and carboxymethyl cellulose.
AB  - In this work, synthetic nanoscale zerovalent iron (NZVI) stabilized with two
      polymers, Starch and Carboxymethyl cellulose (CMC) were examined and compared for
      their ability in removing As (III) and As (V) from aqueous solutions as the most
      promising iron nanoparticles form for arsenic removal. Batch operations were
      conducted with different process parameters such as contact time, nanoparticles
      concentration, initial arsenic concentration and pH. Results revealed that starch
      stabilized particles (S-nZVI) presented an outstanding ability to remove both
      arsenate and arsenite and displayed ~ 36.5% greater removal for As (V) and 30%
      for As (III) in comparison with CMC-stabilized nanoparticles (C-nZVI). However,
      from the particle stabilization viewpoint, there is a clear trade off to choosing
      the best stabilized nanoparticles form. Removal efficiency was enhanced with
      increasing the contact time and iron loading but reduced with increasing initial
      As (III, V) concentrations and pH. Almost complete removal of arsenic (up to 500
      MUg/L) was achieved in just 5 min when the S-nZVI mass concentration was 0.3 g/L
      and initial solution pH of 7 +/- 0.1. The maximum removal efficiency of both
      arsenic species was obtained at pH = 5 +/- 0.1 and starched nanoparticles was
      effective in slightly acidic and natural pH values. The adsorption kinetics
      fitted well with pseudo-second-order model and the adsorption data obeyed the
      Langmuir equation with a maximum adsorption capacity of 14 mg/g for arsenic (V),
      and 12.2 mg/g for arsenic (III). It could be concluded that starch stabilized
      Fe(0) nanoparticles showed remarkable potential for As (III, V) removal from
      aqueous solution e.g. contaminated water. 

PMID- 24860661
TI  - Detection and identification of Legionella species in hospital water supplies
      through Polymerase Chain Reaction (16S rRNA).
AB  - Legionella spp. are important waterborne pathogens that are normally transmitted
      through aerosols. The present work was conducted to investigate the presence of
      Legionella spp. and its common species in hospital water supplies. Considering
      the limitations of culture method, polymerase chain reaction (PCR) assays were
      developed to detect the gene 16S rRNA irrespective of the bacterial serotype.
      Four well-established DNA extraction protocols (freeze & thaw and phenol
      chloroform as two manual protocols and two commercial kits) were tested and
      evaluated to release DNA from bacterial cells. A total of 45 samples were
      collected from seven distinct hospitals' sites during a period of 10 months. The
      PCR assay was used to amplify a 654-bp fragment of the 16S rRNA gene. Legionella
      were detected in 13 samples (28.9%) by all of the methods applied for DNA
      extraction. Significant differences were noted in the yield of extracted nucleic
      acids. Legionella were not detected in any of the samples when DNA extraction by
      freeze & thaw was used. Excluding this method and comparing manual protocol with
      commercial kits, Kappa coefficient was calculated as 0.619 with p < 0.05.
      Although no meaningful differences were found between the kits, DNA extraction
      with Bioneer kit exhibited a higher sensitivity than classical Qiagen.
      Showerheads and cold-water taps were the most and least contaminated sources with
      55.5 and 9 percent positive samples, respectively. Moreover two positive samples
      were identified for species by DNA sequencing and submitted to the Gene Bank
      database with accession Nos. FJ480932 and FJ480933. The results obtained showed
      that despite the advantages of molecular assays in Legionella tracing in
      environmental sources, the use of optimised DNA extraction methods is critical. 

PMID- 24860663
TI  - Influence of an infectious diseases specialist on ICU multidisciplinary rounds.
AB  - Objective. To ascertain the influence of a physician infectious diseases
      specialist (IDS) on antibiotic use in a medical/surgical intensive care unit.
      Method. Over a 5-month period, the antibiotic regimens ordered by the ICU
      multidisciplinary team were studied. The days of antibiotic therapy (DOT) when
      management decisions included an IDS were compared to DOT in the absence of an
      IDS. The associated treatment expense was calculated. Results. Prior to
      multidisciplinary rounds (MDRs), 79-80% of the patients were receiving one or
      more antibiotic. IDS participation occurred in 61 multidisciplinary rounding
      sessions. There were 384 patients who before MDRs had orders for 669 days of
      antimicrobial therapy (DOT). After MDRs, the antimicrobial DOT were reduced to
      511 with a concomitant cost saving of $3772. There were 51 MDR sessions that
      occurred in the absence of the IDS. There were 352 patients who before MDRs had
      orders for 593 DOT. After MDRs, the DOT were reduced to 572 with a cost savings
      of $727. The results were normalized by number of patients evaluated with
      statistically greater reductions when MDRs included the IDS. In addition, the
      number of rounding sessions with a reduction in DOT was greater with the
      participation of the IDS. Conclusion. The addition of an IDS to multidisciplinary
      ICU patient rounds resulted in a reduction in antibiotic DOT and attendant drug
      expense. 

PMID- 24860664
TI  - Prevalence and seroincidence of hepatitis B and hepatitis C infection in high
      risk people who inject drugs in china and Thailand.
AB  - We determined the prevalence and incidence of HBV and HCV infection in people who
      inject drugs (PWIDs) at high risk for HIV in China and Thailand and determined
      the association of HBV and HCV incidence with urine opiate test results and with
      short-term versus long-term buprenorphine-naloxone (B-N) treatment use in a
      randomized clinical trial (HPTN 058). 13.8% of 1049 PWIDs in China and 13.9% of
      201 PWIDs in Thailand were HBsAg positive at baseline. Among HBsAg negative
      participants, the HBsAg incidence rate was 2.7/100 person years in China and
      0/100 person years in Thailand. 81.9% of 1049 PWIDs in China and 59.7% of 201 in
      Thailand were HCV antibody positive at baseline. The HCV confirmed seroincidence
      rate among HCV antibody negative PWIDs was 22/100 person years in China and
      4.6/100 person years in Thailand. Incident HBsAg was not significantly different
      in the short-term versus long-term B-N arm in China or Thailand. Participants
      with positive opiate results in at least 75% of their urines during the time
      period were at increased risk of incident HBsAg (HR = 5.22; 95% CI, 1.08 to
      25.22; P = 0.04) in China, but not incident HCV conversion in China or Thailand. 

PMID- 24860662
TI  - Stem cells' guided gene therapy of cancer: New frontier in personalized and
      targeted therapy.
AB  - INTRODUCTION: Diagnosis and therapy of cancer remain to be the greatest
      challenges for all physicians working in clinical oncology and molecular
      medicine. The statistics speak for themselves with the grim reports of 1,638,910
      men and women diagnosed with cancer and nearly 577,190 patients passed away due
      to cancer in the USA in 2012. For practicing clinicians, who treat patients
      suffering from advanced cancers with contemporary systemic therapies, the main
      challenge is to attain therapeutic efficacy, while minimizing side effects.
      Unfortunately, all contemporary systemic therapies cause side effects. In treated
      patients, these side effects may range from nausea to damaged tissues. In cancer
      survivors, the iatrogenic outcomes of systemic therapies may include genomic
      mutations and their consequences. Therefore, there is an urgent need for
      personalized and targeted therapies. Recently, we reviewed the current status of
      suicide gene therapy for cancer. Herein, we discuss the novel strategy:
      genetically engineered stem cells' guided gene therapy. REVIEW OF THERAPEUTIC
      STRATEGIES IN PRECLINICAL AND CLINICAL TRIALS: Stem cells have the unique
      potential for self renewal and differentiation. This potential is the primary
      reason for introducing them into medicine to regenerate injured or degenerated
      organs, as well as to rejuvenate aging tissues. Recent advances in genetic
      engineering and stem cell research have created the foundations for genetic
      engineering of stem cells as the vectors for delivery of therapeutic transgenes.
      Specifically in oncology, the stem cells are genetically engineered to deliver
      the cell suicide inducing genes selectively to the cancer cells only. Expression
      of the transgenes kills the cancer cells, while leaving healthy cells unaffected.
      Herein, we present various strategies to bioengineer suicide inducing genes and
      stem cell vectors. Moreover, we review results of the main preclinical studies
      and clinical trials. However, the main risk for therapeutic use of stem cells is
      their cancerous transformation. Therefore, we discuss various strategies to
      safeguard stem cell guided gene therapy against iatrogenic cancerogenesis.
      PERSPECTIVES: Defining cancer biomarkers to facilitate early diagnosis,
      elucidating cancer genomics and proteomics with modern tools of next generation
      sequencing, and analyzing patients' gene expression profiles provide essential
      data to elucidate molecular dynamics of cancer and to consider them for crafting
      pharmacogenomics-based personalized therapies. Streamlining of these data into
      genetic engineering of stem cells facilitates their use as the vectors delivering
      therapeutic genes into specific cancer cells. In this realm, stem cells guided
      gene therapy becomes a promising new frontier in personalized and targeted
      therapy of cancer.

PMID- 24860665
TI  - Thicker Carotid Intima Media Thickness in Children with Monocyte Chemoattractant
      Protein-1: A-2138T and A-2464G Mutation.
AB  - Carotid intima media thickness (CIMT) is clearly associated with atherosclerosis.
      Studies in ischemic stroke patients reveal that there is a significant
      association between CIMT with monocyte chemoattractant protein-1 (MCP-1) and
      osteopontin (OPN) promoter polymorphism. This research aims to explain the effect
      of MCP-1 and OPN promoter polymorphism toward CIMT changes identified in Javanese
      Indonesian children. Subjects were 54 children: 27 were from parents with
      ischemic stroke (cases), and 27 were from healthy parents (controlled). The CIMT
      was examined by utilizing high resolution B-mode ultrasound. Physical examination
      and genotyping analysis of MCP-1 promoter were conducted by employing PCR method.
      Research results indicate that two polymorphisms were obtained, that is, A-2138T
      and G-2464A, respectively. A-2138T polymorphism was found in 5% of case children
      and in 14.3% of controlled children. G-2464A polymorphism was found in 5% of case
      children. CIMT of case children was significantly different from that of
      controlled children (0.61 +/- 0.012 mm versus, 0.52 +/- 0.015 mm, P = 0.021).
      Subjects with MCP-1 promoter polymorphism have 1.471 times higher tendency to
      have thicker CIMT than subjects with no polymorphism in MCP1 promoter. OPN
      promoter T-66G was also studied but it did not indicate occurrence of
      polymorphism in samples. 

PMID- 24860666
TI  - Long-Term Effect of Interactive Online Dietician Weight Loss Advice in General
      Practice (LIVA) Protocol for a Randomized Controlled Trial.
AB  - Background. Internet-based complex interventions aiming to promote weight loss
      and optimize healthy behaviors have attracted much attention. However, evidence
      for effect is lacking. Obesity is a growing problem, resulting in an increasing
      demand for cost efficient weight loss programs suitable for use on a large scale,
      for example, as part of standard primary care. In a previous pilot project by
      Brandt et al. (2011) without a control group, we examined the effects of online
      dietician counseling and found an average weight loss of 7.0 kg (95% CI: 4.6 to
      9.3 kg) after 20 months. Aims and Methods. To analyze the effects of a complex
      intervention using trained dieticians in a general practice setting combined with
      internet-based interactive and personalized weight management support compared
      with conventional advice with a noninteractive internet support as placebo
      treatment in 340 overweight patients during a 2-year period. Primary endpoints
      are weight loss and lowering of cholesterol (LDL). We will also explore patients'
      sociodemographics and use of the intervention as well as the health
      professionals' views and perceptions of the intervention (their role and the
      advice and support that they provide). Perspective. The project will generate
      knowledge on the cost-effectiveness of a complex internet-based intervention in a
      general practice setting and on barriers and acceptability among professionals
      and patients. 

PMID- 24860667
TI  - A Nonhost Peptidase Inhibitor of ~14 kDa from Butea monosperma (Lam.) Taub. Seeds
      Affects Negatively the Growth and Developmental Physiology of Helicoverpa
      armigera.
AB  - Helicoverpa armigera is one of the major devastating pests of crop plants. In
      this context a serine peptidase inhibitor purified from the seeds of Butea
      monosperma was evaluated for its effect on developmental physiology of H.
      armigera larvae. B. monosperma peptidase inhibitor on 12% denaturing
      polyacrylamide gel electrophoresis exhibited a single protein band of ~14 kDa
      with or without reduction. In vitro studies towards total gut proteolytic enzymes
      of H. armigera and bovine trypsin indicated measurable inhibitory activity. B.
      monosperma peptidase inhibitor dose for 50% mortality and weight reduction by 50%
      were 0.5% w/w and 0.10% w/w, respectively. The IC50 of B. monosperma peptidase
      inhibitor against total H. armigera gut proteinases activity was 2.0 ug/mL. The
      larval feeding assays suggested B. monosperma peptidase inhibitor to be toxic as
      reflected by its retarded growth and development, consequently affecting
      fertility and fecundity of pest and prolonging the larval-pupal duration of the
      insect life cycle of H. armigera. Supplementing B. monosperma peptidase inhibitor
      in artificial diet at 0.1% w/w, both the efficiencies of conversion of ingested
      as well as digested food were downregulated, whereas approximate digestibility
      and metabolic cost were enhanced. The efficacy of Butea monosperma peptidase
      inhibitor against progressive growth and development of H. armigera suggest its
      usefulness in insect pest management of food crops. 

PMID- 24860668
TI  - Association between Smoking and Health Outcomes in Postmenopausal Women Living
      with Multiple Sclerosis.
AB  - Background. In multiple sclerosis (MS), symptom management and improved health
      related quality of life (HrQOL) may be modified by smoking. Objective. To
      evaluate the extent to which smoking is associated with worsened health outcomes
      and HrQOL for postmenopausal women with MS. Methods. We identified 251 Women's
      Health Initiative Observational Study participants with a self-reported MS
      diagnosis. Using a linear model, we estimated changes from baseline to 3 years
      for activities of daily living, total metabolic equivalent tasks (MET) hours per
      week, mental and physical component scales (MCS, PCS) of the SF-36, and
      menopausal symptoms adjusting for years since menopause and other confounders.
      Results. Nine percent were current and 50% past smokers. Age at smoking
      initiation was associated with significant changes in MCS during menopause. PCS
      scores were unchanged. While women who had ever smoked experienced an increase in
      physical activity during menopause, the physical activity levels of women who
      never smoked declined. Residual confounding may explain this finding. Smoking was
      not associated with change in menopausal symptoms during the 3-year follow-up.
      Conclusion. Smoking was not associated with health outcomes among post-menopausal
      women with MS. 

PMID- 24860669
TI  - Vascular Response to Graded Angiotensin II Infusion in Offspring Subjected to
      High-Salt Drinking Water during Pregnancy: The Effect of Blood Pressure, Heart
      Rate, Urine Output, Endothelial Permeability, and Gender.
AB  - Introduction. Rennin-angiotensin system and salt diet play important roles in
      blood pressure control. We hypothesized that the high-salt intake during
      pregnancy influences the degree of angiotensin-dependent control of the blood
      pressure in adult offspring. Methods. Female Wistar rats in two groups (A and B)
      were subjected to drink tap and salt water, respectively, during pregnancy. The
      offspring were divided into four groups as male and female offspring from group A
      (groups 1 and 2) and from group B (groups 3 and 4). In anesthetized matured
      offspring mean arterial pressure (MAP), heart rate and urine output were measured
      in response to angiotensin II (AngII) (0-1000 ng/kg/min, iv) infusion. Results.
      An increase in MAP was detected in mothers with salt drinking water (P < 0.05).
      The body weight increased and kidney weight decreased significantly in male
      offspring from group 3 in comparison to group 1 (P < 0.05). MAP and urine volume
      in response to AngII infusion increased in group 3 (P < 0.05). These findings
      were not observed in female rats. Conclusion. Salt overloading during pregnancy
      had long-term effects on kidney weight and increased sex-dependent response to
      AngII infusion in offspring (adult) that may reveal the important role of diet
      during pregnancy in AngII receptors. 

PMID- 24860670
TI  - Combination of Complement-Dependent Cytotoxicity and Relative Fluorescent
      Quantification of HLA Length Polymorphisms Facilitates the Detection of a Loss of
      Heterozygosity.
AB  - Loss of heterozygosity (LOH) is a common event in malignant cells. In this work
      we introduce a new approach to identify patients with loss of heterozygosity in
      the HLA region either at first diagnosis or after HLA mismatched allogeneic HSCT.
      Diagnosis of LOH requires a high purity of recipient target cells. FACS is time
      consuming and also frequently prevented by rather nonspecific or unknown immune
      phenotype. The approach for recipient cell enrichment is based on HLA targeted
      complement-dependent cytotoxicity (CDC). Relative fluorescent quantification
      (RFQ) analysis of HLA intron length polymorphisms then allows analysis of HLA
      heterozygosity. The approach is exemplified in recent clinical cases illustrating
      the detection of an acquired allele loss. As illustrated in one case with DPB1,
      distinct HLA loci in donor and patient were sufficient for both proof of donor
      cell removal and evaluation of allele loss in the patient's leukemic cells.
      Results were confirmed using HLA-B RFQ analysis and leukemia-associated aberrant
      immunophenotype (LAIP) based cell sort. Both results confirmed suspected loss of
      HLA heterozygosity. Our approach complements or substitutes for FACS-based cell
      enrichment; hence it may be further developed as novel routine diagnostic tool.
      This allows rapid recipient cell purification and testing for loss of HLA
      heterozygosity before and after allogeneic HSCT in easily accessible peripheral
      blood samples. 

PMID- 24860671
TI  - Biocontrol Activity of the Local Strain of Metschnikowia pulcherrima on Different
      Postharvest Pathogens.
AB  - The strains of the yeast Metschnikowia pulcherrima have strong biocontrol
      activity against various microorganisms. Biocontrol activity of M. pulcherrima
      largely depends on its iron immobilizing pigment pulcherrimin. Biocontrol
      activity of pulcherrimin producing strain, M. pulcherrima UMY15, isolated from
      local vineyards, was tested on different molds that cause food spoilage. M.
      pulcherrima UMY15 was a very effective biocontrol agent against Penicillium
      roqueforti, P. italicum, P. expansum, and Aspergillus oryzae in in-vitro plate
      tests. However, the inhibitory activity of M. pulcherrima UMY15 was less
      effective on Fusarium sp. and A. niger species in biocontrol assays. In addition,
      M. pulcherrima UMY15 strain completely inhibited the germination and mycelia
      growth of A. oryzae, A. parasiticus, and Fusarium sp. spores on artificial wounds
      of apples when they coinoculated with M. pulcherrima UMY15. Moreover, when
      coinoculated, M. pulcherrima UMY15 strain also inhibited the growth of P.
      roqueforti, P. italicum, P. expansum, A. oryzae, Fusarium sp., and Rhizopus sp.
      in grape juice, indicating that M. pulcherrima UMY15 can be used as a very
      effective biocontrol yeast against various species of postharvest pathogens,
      including Penicillium, Aspergillus, Fusarium, and Rhizopus. 

PMID- 24860672
TI  - Histological Characterization of Biliary Intraepithelial Neoplasia with respect
      to Pancreatic Intraepithelial Neoplasia.
AB  - Biliary intraepithelial neoplasia (BilIN) is a precursor lesion of
      hilar/perihilar and extrahepatic cholangiocarcinoma. BilIN represents the process
      of multistep cholangiocarcinogenesis and is the biliary counterpart of pancreatic
      intraepithelial neoplasia (PanIN). This study was performed to clarify the
      histological characteristics of BilIN in relation to PanIN. Using paraffin
      embedded tissue sections of surgically resected specimens of cholangiocarcinoma
      associated with BilIN and pancreatic ductal adenocarcinoma associated with PanIN,
      immunohistochemical staining was performed using primary antibodies against MUC1,
      MUC2, MUC5AC, cyclin D1, p21, p53, and S100P. For mucin staining, Alcian blue pH
      2.5 was used. Most of the molecules examined here showed similar expression
      patterns in BilIN and PanIN, in which their expression tended to increase along
      with the increase in atypia of the epithelial lesions. Significant differences
      were observed in the increase in mucin production and the expression of S100P in
      PanIN-1 and the expression of p53 in PanIN-3, when compared with those in BilIN
      of a corresponding grade. These results suggest that cholangiocarcinoma and
      pancreatic ductal adenocarcinoma share, at least in part, a common carcinogenic
      process and further confirm that BilIN can be regarded as the biliary counterpart
      of PanIN. 

PMID- 24860674
TI  - Endoscopic Endonasal Approach for Resection of Infundibular Granular Cell Tumor:
      Case Report and Literature Review.
AB  - Granular cell tumors of the pituitary and infundibular stalk are rare, slow
      growing tumors. Although usually asymptomatic, neurological deficits with
      chiasmatic compression can lead to clinical presentation. We describe a case in
      which a purely endoscopic endonasal approach was used for complete resection of
      an infundibular granular cell tumor with skull base reconstruction with a
      pedicled nasoseptal flap. Final pathology confirmed the diagnosis and 24 month
      follow up revealed no recurrence of the tumor with continued improvement in the
      patient's vision. This diagnosis must be entertained for masses noted in the
      sellar/suprasellar region. Immunohistochemistry and radiographic findings help
      lead to an accurate diagnosis. Complete surgical resection remains the mainstay
      of treatment in symptomatic patients, as published reports indicate little value
      with adjuvant radiation therapy and poor long term control. The complication of
      panhypopituitarism can often result following complete resection and patients
      need to be counseled with the risks of treatment. A purely endoscopic endonasal
      approach was safe and effective and should be attempted only by experienced skull
      base centers.

PMID- 24860675
TI  - Hyperostotic Esthesioneuroblastoma.
AB  - Esthesioneuroblastomas are rare, soft-tissue tumors that can often extend from
      the sinonasal cavity into the intracranial and orbital space. Prognosis depends
      upon the histological grade and location/extent of the tumor. Treatment often
      consists of maximum surgical resection followed by adjuvant chemoradiation
      therapy. We present a case of a patient with esthesioneuroblastoma accompanied by
      an extensive osteoblastic reaction leading to significant hyperostosis along the
      skull base. His presenting symptoms included diplopia, and imaging revealed
      invasion of the orbital and intracranial spaces. Although a gross total resection
      of the soft tissue component of the tumor was achieved, a complete removal of the
      involved hyperostotic skull base could not be performed despite endoscopic
      endonasal and bifrontal craniotomy approaches in the same operative setting.
      Symptomatically, the patient improved and went on to receive chemoradiation
      therapy; he remains clinically and radiographically stable at 12 months.
      Investigation into the genetics and immunohistochemistry of this rare,
      hyperostotic variant of estheioneuroblastoma may provide details regarding its
      aggressive nature.

PMID- 24860673
TI  - What are the precursor and early lesions of peripheral intrahepatic
      cholangiocarcinoma?
AB  - Cholangiocarcinoma (CC) is divided into distal, perihilar, and intrahepatic CCs
      (ICCS), and are further subdivided into large bile duct ICC and peripheral ICC.
      In distal and perihilar CC and large duct ICC, biliary intraepithelial neoplasm
      (BilIN) and intraductal papillary neoplasm (IPN) have been proposed as precursor
      lesions. Peripheral ICC, bile duct adenoma (BDA), biliary adenofibroma (BAF), and
      von Meyenburg complexes (VMCs) are reportedly followed by development of ICCs.
      Herein, we surveyed these candidate precursor lesions in the background liver of
      37 cases of peripheral ICC and controls (perihilar CC, 34 cases; hepatocellular
      carcinoma, 34 cases and combined hepatocellular cholangiocarcinoma, 25 cases). In
      the background liver of peripheral ICC, BDA and BAF were not found, but there
      were not infrequently foci of BDA-like lesions and atypical bile duct lesions
      involving small bile ducts (32.4% and 10.8%, resp.). VMCs were equally found in
      peripheral CCs and also control CCs. In conclusion, BDA, BAF, and VMCs are a
      possible precursor lesion of a minority of peripheral CCs, and BDA-like lesions
      and atypical bile duct lesions involving small bile ducts may also be related to
      the development of peripheral ICC. Further pathologic studies on these lesions
      are warranted for analysis of development of peripheral ICCs. 

PMID- 24860676
TI  - McConnell Sign in a Patient with Massive Acute Pulmonary Embolism.
AB  - A 48-year-old female was admitted after experiencing a brief syncopal episode.
      Three weeks ago the patient sustained a right arm humerus bone fracture in a
      motor vehicle accident. Since the accident, her mobility has been limited. CT
      angiogram of the chest revealed massive bilateral pulmonary emboli. A 2D
      echocardiogram was performed, which demonstrated McConnell sign and severe right
      ventricle dysfunction. Considering potential of hemodynamic instability, the
      patient received fibrinolytic therapy with Alteplase. A subsequent 2D
      echocardiogram showed complete resolution of McConnell sign and right ventricle
      dysfunction. 

PMID- 24860677
TI  - Pulmonary Balloon Valvuloplasty during Pregnancy.
AB  - Women with valvular heart disease have an increased risk of adverse outcomes in
      pregnancy; however, with appropriate evaluation and treatment, most women can
      successfully bear healthy children. During pregnancy, pulmonary stenosis is
      generally well tolerated in the absence of other haemodynamically significant
      lesions. We present a case of a multiparous woman,who is pregnant with her sixth
      child, with a severe pulmonary stenosis. She presented with exertional chest pain
      and dyspnea. She was managed successfully with balloon valvuloplasty. 

PMID- 24860678
TI  - Guillain-Barre Syndrome due to CMV Reactivation after Cardiac Transplantation.
AB  - A 40-year-old male patient suffered from end-stage heart failure due to ischemic
      cardiomyopathy and received orthotopic cardiac transplantation in June 2005. The
      instantaneous postoperative course was uneventful, but, seven months later, he
      suffered from paralysis in the lower extremities finally resulting in
      quadriplegia and was admitted to hospital. After laboratory testings the
      diagnosis of a Guillain-Barre syndrome due to cytomegalovirus reactivation was
      confirmed. 

PMID- 24860679
TI  - Omental herniation: a rare complication of vacuum-assisted closure of infected
      sternotomy wound.
AB  - Vacuum-assisted closure (VAC) has recently been adopted as an acceptable modality
      for management of sternotomy wound infections. Although generally efficacious,
      the use of negative pressure devices has been associated with complications such
      as bleeding, retention of sponge, and empyema. We report the first case of
      greater omental hernia as a rare complication of vacuum-assisted closure of
      sternal wound infection following coronary artery bypass grafting. 

PMID- 24860680
TI  - Coronary anomalies: left main coronary artery aneurysm.
AB  - Coronary artery aneurysm is one of the rarest anomalies that we see in our
      medical practice and they are mostly associated with obstructive lesions due to
      atherosclerotic changes. Management of these aneurysm patients (conservative or
      surgical repair) usually depends on obstructive lesions and associated symptoms.
      We are presenting a case of left main aneurysm measuring around 14 * 28 mm with
      other obstructive leisons. It was treated with surgical repair in view of
      obstructive lesions and symptoms. 

PMID- 24860681
TI  - Fatal heat stroke in a schizophrenic patient.
AB  - Objective. The case of a patient who developed a fatal post-exertional heat
      stroke is reported. Case Report. A 20-year-old man with a history of morbid
      obesity, hypertension, and schizophrenia was admitted to our intensive care unit
      because of multiorgan failure due to severe heat stroke. He had been working
      under the sun. Treatment included aggressive body cooling but, in spite of the
      best supportive care, the patient succumbed in a few hours. We concluded that the
      adverse event was possibly associated with his obesity and the use of
      antipsychotics. Histological evaluation revealed lesions consistent with severe
      hyperthermia and shock. Conclusions. Heat stroke is an uncommon clinical entity
      characterized by systemic heat and loss of the body's normal mechanisms for
      dealing with heat stress, such as sweating and temperature control. When heat
      stroke is diagnosed early and supportive care begins promptly the prognosis is
      optimal but it becomes a life-threatening disease when treatment is delayed. Lack
      of physical acclimatization and the use of certain medications that interfere
      with salt and water balance can impair thermoregulation under conditions of high
      environmental temperature. Health professionals must be adequately prepared to
      prevent, recognise, and treat them urgently. 

PMID- 24860682
TI  - The rendu-osler-weber disease revealed by a refractory hypoxemia and severe
      cerebral fat embolism.
AB  - The Rendu-Osler-Weber disease is a genetic disease which may lead to severe
      hemorrhage and less frequently to severe organ dysfunction. We report the case of
      a 22-year-old patient with no personal medical history who was involved in a
      motorcycle accident and exhibited severe complications related to large
      arteriovenous pulmonary shunts during his ICU stay. The patient developed an
      unexplained severe hypoxemia which was attributed to several arteriovenous shunts
      of the pulmonary vasculature by a contrast study during a transesophageal
      echocardiographic examination. The course was subsequently complicated by a
      prolonged coma associated with hemiplegia which was attributed to a massive
      paradoxical fat embolism in the setting of an untreated femoral fracture. In
      addition to hemorrhagic complications which may lead to intractable shock,
      arteriovenous malformations associated with the Rendu-Osler-Weber disease may
      involve the pulmonary vasculature and result in unexpected complications, such as
      hypoxemia or severe cerebral fat embolism in high-risk patients. 

PMID- 24860683
TI  - Neurofibroma of the palate.
AB  - Neurofibroma is a benign peripheral nerve sheath tumor comprising variable
      mixture of Schwann cells, perineurial-like cells, and fibroblasts. Neurofibroma
      may occur as solitary lesion or as part of a generalised syndrome of
      neurofibromatosis or very rarely as multiple neurofibromas without any associated
      syndrome. There are two distinct variants of neurofibromatosis type I and type
      II. We present a case of neurofibroma of the hard palate associated with
      neurofibromatosis type I. The diagnosis of the lesion was made based on the
      clinical findings, family history, histopathology, and immunohistochemistry.
      Literature was reviewed and different types of neurofibroma, their incidence and
      frequency in the oral cavity, its association with neurofibromatosis, clinical
      manifestations, histopathologic characteristics, immunohistochemical analysis,
      behaviour, treatment, and recurrence are discussed. 

PMID- 24860684
TI  - Metachronous bilateral isolated adrenal metastasis from rectal adenocarcinoma: a
      case report.
AB  - We report a case of adrenal metastasis from colorectal cancer in a 54-year-old
      woman. Nine months after resection for advanced rectal carcinoma, a computed
      tomography scan revealed bilateral adrenal metastasis. The level of serum
      carcinoembryonic antigen was normal. A bilateral adrenalectomy was performed
      after chemotherapy. Histopathological examination showed adenocarcinoma,
      compatible with metastasis from the rectal cancer. Adrenal metastasis should be
      considered in the patients' follow-up for colorectal cancer. 

PMID- 24860685
TI  - Evaluation of a low-threshold/high-tolerance methadone maintenance treatment
      clinic in saint john, new brunswick, Canada: one year retention rate and illicit
      drug use.
AB  - Objective. To report the one-year retention rate and the prevalence of illicit
      opioid use and cocaine use in the Low-Threshold/High-Tolerance (LTHT) methadone
      maintenance treatment (MMT) clinic located in Saint John, New Brunswick, Canada.
      Methods. A description of the LTHT MMT clinic is provided. The one-year retention
      rate was determined by collecting data on patients who enrolled in the LTHT MMT
      clinic between August 04, 2009 and August 04, 2010. The prevalence of illicit
      drug use was determined using a randomly selected retrospective cohort of 84
      participants. For each participant the results of six consecutive urine tests for
      the most recent three months were compared to the results of the first six
      consecutive urine tests after program entry. Results. The one-year retention rate
      was 95%, 67% of the cohort achieved abstinence from illicit opioids and an
      additional 13% abstained from cocaine use. Conclusion. The novel feature of the
      LTHT MMT clinic is that patients are not denied methadone because of lack of
      ancillary services. Traditional comprehensive MMT programs invest the majority of
      financial resources in ancillary services that support the biopsychosocial model,
      whereas the LTHT approach utilizes a medical model and directs resources at
      medical management. 

PMID- 24860686
TI  - Prevalence and Incidence of Syphilis among Volunteer Blood Donors in Israel.
AB  - Data of 1,290,222 volunteer blood donors, in a 5-year period, was analyzed for
      prevalence and incidence of syphilis. Subsequent testing of donations positive in
      Treponema pallidum hemagglutination assay included Venereal Disease Research
      Laboratory and fluorescent Treponemal antibody absorption. Stepwise logistic
      regression model was used to identify positive syphilis serology. Prevalence of
      syphilis was 47 : 100,000, similar in men and women and increased significantly
      with age (P < 0.001). Native Israelis had the lowest prevalence rate of syphilis
      (21 : 100,000), while a significantly higher prevalence was found among
      immigrants from Africa, Eastern Europe, and South America (odds ratios of 19.0,
      10.8, and 7.3, resp., P < 0.001 for each). About 33.2% of the seropositive donors
      had evidence of recent infection, and 66.8% had past infections. Incidence rate
      reached 8 : 100,000 person-years. Coinfection with HIV, HCV, and HBV was
      calculated as 8%, 1.88%, and 0.37% for positive donations, respectively. The data
      support the need to continue screening blood donors in Israel for syphilis and
      employ preventive measures to populations at risk, in order to improve public
      health, blood safety, and quality. A subsequent study to assess blood donors'
      knowledge, attitude, and behavior is planned. In times of global migration this
      information may be useful to blood services worldwide. 

PMID- 24860687
TI  - Synthesis of chirally pure 1-deoxy-d-xylulose-5-phosphate : A substrate for IspC
      assay to determine M. tb inhibitor.
AB  - 1-Deoxy-D-xylulsose-5-phosphate (DXP) is a key intermediate in the non-mevalonate
      or methyl erythritol phosphate (MEP) pathway for the biosynthesis of isoprenoid,
      which are essential building blocks involved in the construction of pathogens
      growth. Since the homologous enzymes of this pathway are not present in
      vertebrates, including humans, the MEP pathway presents a viable source for
      antimicrobial drug targets. However, an insight into the features of the enzymes
      involved in this pathway has been plagued by lack of chirally pure substrates.
      Here in, we report an efficient synthesis of enantiomerically pure 1-deoxy-D
      xylulose-5-phosphate from commercially available 1,2-O-isopropylidene-alpha-D
      xylofuranose through Weinreb amide formation in shorter route.

PMID- 24860688
TI  - Creating a pipeline of talent for informatics: STEM initiative for high school
      students in computer science, biology, and biomedical informatics.
AB  - This editorial provides insights into how informatics can attract highly trained
      students by involving them in science, technology, engineering, and math (STEM)
      training at the high school level and continuing to provide mentorship and
      research opportunities through the formative years of their education. Our
      central premise is that the trajectory necessary to be expert in the emergent
      fields in front of them requires acceleration at an early time point. Both
      pathology (and biomedical) informatics are new disciplines which would benefit
      from involvement by students at an early stage of their education. In 2009,
      Michael T Lotze MD, Kirsten Livesey (then a medical student, now a medical
      resident at University of Pittsburgh Medical Center (UPMC)), Richard
      Hersheberger, PhD (Currently, Dean at Roswell Park), and Megan Seippel, MS (the
      administrator) launched the University of Pittsburgh Cancer Institute (UPCI)
      Summer Academy to bring high school students for an 8 week summer academy focused
      on Cancer Biology. Initially, pathology and biomedical informatics were involved
      only in the classroom component of the UPCI Summer Academy. In 2011, due to
      popular interest, an informatics track called Computer Science, Biology and
      Biomedical Informatics (CoSBBI) was launched. CoSBBI currently acts as a feeder
      program for the undergraduate degree program in bioinformatics at the University
      of Pittsburgh, which is a joint degree offered by the Departments of Biology and
      Computer Science. We believe training in bioinformatics is the best foundation
      for students interested in future careers in pathology informatics or biomedical
      informatics. We describe our approach to the recruitment, training and research
      mentoring of high school students to create a pipeline of exceptionally well
      trained applicants for both the disciplines of pathology informatics and
      biomedical informatics. We emphasize here how mentoring of high school students
      in pathology informatics and biomedical informatics will be critical to assuring
      their success as leaders in the era of big data and personalized medicine. 

PMID- 24860689
TI  - Using Think Aloud Protocols to Assess E-Prescribing in Community Pharmacies.
AB  - INTRODUCTION: Think aloud protocol has rarely been used as a method of data
      collection in community pharmacies. PURPOSE: The aim of the report is to describe
      how think aloud protocols were used to identify issues that arise when using e
      prescribing technology in pharmacies. In this paper, we report on the benefits
      and challenges of using think aloud protocols in pharmacies to examine the use of
      e-prescribing systems. METHODS: Sixteen pharmacists and pharmacy technicians were
      recruited from seven community pharmacies in Wisconsin. Data were collected using
      direct observation alongside think aloud protocol. Direct observations and think
      aloud protocols took place between January-February, 2011. Participants were
      asked to verbalize their thoughts as they process electronic prescriptions.
      RESULTS: Participants identify weaknesses in e-prescribing that they had
      previously not conceived. This created heightened awareness for vigilance when
      processing e-prescriptions. The main challenge with using think aloud protocols
      were interruptions in the pharmacy. Some participants found it difficult to
      remember to continue verbalizing during think aloud sessions. CONCLUSION: The use
      of think aloud protocols as method of data collection is a new way for
      understanding the issues related to technology use in community pharmacy
      practice. Think aloud protocol was beneficial in providing objective information
      on e-prescribing not based on pharmacist's or technician's opinion of the
      technology. This method provided detailed information and also a wide variety of
      real time challenges with e-prescribing technology in community pharmacies. Using
      this data collection method can help identify potential patient safety issues
      when using e-prescribing and suggestions for redesign.

PMID- 24860690
TI  - Phylogenetic Analysis of Guinea 2014 EBOV Ebolavirus Outbreak.
AB  - Members of the genus Ebolavirus have caused outbreaks of haemorrhagic fever in
      humans in Africa. The most recent outbreak in Guinea, which began in February of
      2014, is still ongoing. Recently published analyses of sequences from this
      outbreak suggest that the outbreak in Guinea is caused by a divergent lineage of
      Zaire ebolavirus. We report evidence that points to the same Zaire ebolavirus
      lineage that has previously caused outbreaks in the Democratic Republic of Congo,
      the Republic of Congo and Gabon as the culprit behind the outbreak in Guinea. 

PMID- 24860691
TI  - Differential Expression of HrtA1 and ADAM12 in Placentas from Preeclamptic and
      Normotensive Pregnancies.
AB  - BACKGROUND: High temperature requirement factor A 1 (HtrA1) and a disintegrin and
      metalloproteinase 12 (ADAM12), which play roles in placental implantation and
      placental growth, have been implicated in the pathogenesis of preeclampsia.
      METHODS: We investigated relative mRNA expression of both genes in placental
      tissues from women with preeclampsia (N=18) (average gestational age 36 weeks)
      and an equal number of women with normotensive pregnancies (average gestational
      age 39 weeks). Real-time polymerase chain reaction was used to measure mRNA
      extracted from term placental biopsies. Differential gene expression was
      evaluated using Student's T-test and fold change analyses. RESULTS: Statistically
      significant increases in placental HtRA1 (1.69-fold, p=0.030) and ADAM12 (1.48
      fold, p=0.010) mRNA expression were observed among preeclamptic cases as compared
      with normotensive controls. HtrA1 expression was correlated with maternal age (p
      value <0.01) among preeclampsia cases. CONCLUSION: Increases in HtRA1 and ADAM12
      placental gene expression in placentas from preeclamptic pregnancies are
      consistent with some earlier reports of altered serum protein concentrations in
      preeclamptic pregnancies. This adds to the literature suggesting that defects in
      placentation (e.g. involving trophoblast invasion) are of etiologic importance in
      preeclampsia.

PMID- 24860693
TI  - Novel insights into the disease etiology of laminopathies.
AB  - Laminopathies are a heterogeneous group of diseases that are caused by mutations
      in the nuclear envelope proteins lamins A and C. Laminopathies include dilated
      cardiomyopathy, Emery-Dreifuss muscular dystrophy, and familial partial
      lipodystrophy. Despite their near-ubiquitous expression, most laminopathies
      involve highly tissue-specific phenotypes, often affecting skeletal and cardiac
      muscle. The underlying mechanism(s) remain incompletely understood. We recently
      reported that altered actin dynamics in lamin A/C-deficient and mutant cells
      disturb nuclear shuttling of the transcriptional co-activator MKL1, which is
      critical for cardiac function. Expression of the inner nuclear membrane protein
      emerin rescues MKL1 translocation through modulating actin dynamics. Here, we
      elaborate on these findings, discuss new insights into the role of nuclear actin
      in MKL1activity, and demonstrate that primary human skin fibroblasts from a
      patient with dilated cardiomyopathy have impaired MKL1 nuclear translocation.
      These findings further strengthen the relevance of impaired MKL1 signaling as a
      potential contributor to the disease mechanism in laminopathies. 

PMID- 24860694
TI  - An interactive three dimensional approach to anatomical description-the jaw
      musculature of the Australian laughing kookaburra (Dacelo novaeguineae).
AB  - The investigation of form-function relationships requires a detailed
      understanding of anatomical systems. Here we document the 3-dimensional
      morphology of the cranial musculoskeletal anatomy in the Australian Laughing
      Kookaburra Dacelo novaeguineae, with a focus upon the geometry and attachments of
      the jaw muscles in this species. The head of a deceased specimen was CT scanned,
      and an accurate 3D representation of the skull and jaw muscles was generated
      through manual segmentation of the CT scan images, and augmented by dissection of
      the specimen. We identified 14 major jaw muscles: 6 in the temporal group (M.
      adductor mandibulae and M. pseudotemporalis), 7 in the pterygoid group (M.
      pterygoideus dorsalis and M. pterygoideus ventralis), and the single jaw abductor
      M. depressor mandibulae. Previous descriptions of avian jaw musculature are
      hindered by limited visual representation and inconsistency in the nomenclature.
      To address these issues, we: (1) present the 3D model produced from the
      segmentation process as a digital, fully interactive model in the form of an
      embedded 3D image, which can be viewed from any angle, and within which major
      components can be set as opaque, transparent, or hidden, allowing the anatomy to
      be visualised as required to provide a detailed understanding of the jaw anatomy;
      (2) provide a summary of the nomenclature used throughout the avian jaw muscle
      literature. The approach presented here provides considerable advantages for the
      documentation and communication of detailed anatomical structures in a wide range
      of taxa. 

PMID- 24860692
TI  - Expression and diagnostic values of calretinin and CK5/6 in cholangiocarcinoma.
AB  - BACKGROUND: Mesothelin, a mesothelial marker, has been found expressed in and as
      a potential treatment target of cholangioacarcinoma (CC). It is possible that CC
      may be derived from the cells sharing mesothelial markers. However, the
      expression of other mesothelial markers in CC is largely unknown. METHODS: Thirty
      CC cases (10 extrahepatic and 20 intrahepatic) were retrieved from our
      institutional archive. The immunohistochemical study of Calretinin (DC8), WT1 (6F
      H2), Lymphatic Endothelial Marker (D2-40), CK5/6 (D5/16 B4) and CK19 (b170) was
      done on formalin fixed paraffin embedded sections for 2-3 blocks of each case. We
      compared the expression levels between CC and normal bile duct (NBD) on the same
      block. RESULTS: All of the CC and NBD are positive for CK19 (23/23) and negative
      for WT1 (0/23) and D2-40 (0/23), except one CC positive for D2-40(1/30, 3.3%) and
      one NBD positive for WT1 (1/23, 4.3%). Calretinin immunoreactivity was detected
      in 52.2% (12/23) of CC, but none in NBD (0/23). CK5/6 was also detectable in
      73.3% (22/30) of CC and all NBD (30/30). Increased expression of calretinin and
      reduced expression of CK5/6 were more likely associated with CC than NBD (P <
      0.001 and P = 0.002, respectively). The sequential staining pattern of positive
      calretinin and negative CK5/6 in calretinin negative cases has a sensitivity of
      69.57% and a specificity of 100% for differentiating CC from NBD. CK5/6
      expression was also more likely associated with well-differentiated CC (7/7
      versus 12/20 in moderately differentiated, and 9/10 in poorly differentiated, P =
      0.019) and extrahepatic CC (10/10 versus 12/20 in intrahepatic, P = 0.029), but
      there was no association between the calretinin expression and the CC grade or
      location. CONCLUSION: Calretinin and CK5/6 immunohistochemical stains may be
      useful for diagnosing a CC. Their immunohistochemical results should be
      interpreted with caution in the cases with differential diagnoses of mesothelioma
      and CC. A full mesothelioma panel, including WT1 and/or D2-40, is recommended to
      better define a mesothelial lineage. The biology of calretinin and CK5/6
      expression in CC is unclear, but might shed light on identifying therapeutic
      targets for CC.

PMID- 24860696
TI  - Assessing the impact of human trampling on vegetation: a systematic review and
      meta-analysis of experimental evidence.
AB  - Vegetation trampling resulting from recreation can adversely impact natural
      habitats, leading to the loss of vegetation and the degradation of plant
      communities. A considerable primary literature exists on this topic, therefore it
      is important to assess whether this accumulated evidence can be used to reach
      general conclusions concerning vegetation vulnerability to inform conservation
      management decisions. Experimental trampling studies on a global scale were
      retrieved using a systematic review methodology and synthesised using random
      effects meta-analysis. The relationships between vegetation recovery and each of
      initial vegetation resistance, trampling intensity, time for recovery, Raunkiaer
      life-form (perennating bud position), and habitat were tested using random
      effects multiple meta-regressions and subgroup analyses. The systematic search
      yielded 304 studies; of these, nine reported relevant randomized controlled
      experiments, providing 188 vegetation recovery effect sizes for analysis. The
      synthesis indicated there was significant heterogeneity in the impact of
      trampling on vegetation recovery. This was related to resistance and recovery
      time, and the interactions of these variables with Raunkiaer life-form, but was
      not strongly dependent on the intensity of the trampling experienced. The
      available evidence suggests that vegetation dominated by hemicryptophytes and
      geophytes recovers from trampling to a greater extent than vegetation dominated
      by other life-forms. Variation in effect within the chamaephyte, hemicryptophyte
      and geophyte life-form sub-groups was also explained by the initial resistance of
      vegetation to trampling, but not by trampling intensity. Intrinsic properties of
      plant communities appear to be the most important factors determining the
      response of vegetation to trampling disturbance. Specifically, the dominant
      Raunkiaer life-form of a plant community accounts for more variation in the
      resilience of communities to trampling than the intensity of the trampling
      experienced, suggesting that simple assessments based on this trait could guide
      decisions concerning sustainable access to natural areas. Methodological and
      reporting limitations must be overcome before more disparate types of evidence
      can be synthesised; this would enable more reliable extrapolation to non-study
      situations, and a more comprehensive understanding of how assessments of
      intrinsic plant traits can be used to underpin conservation management decisions
      concerning access. 

PMID- 24860695
TI  - The complex hybrid origins of the root knot nematodes revealed through
      comparative genomics.
AB  - Root knot nematodes (RKN) can infect most of the world's agricultural crop
      species and are among the most important of all plant pathogens. As yet however
      we have little understanding of their origins or the genomic basis of their
      extreme polyphagy. The most damaging pathogens reproduce by obligatory mitotic
      parthenogenesis and it has been suggested that these species originated from
      interspecific hybridizations between unknown parental taxa. We have sequenced the
      genome of the diploid meiotic parthenogen Meloidogyne floridensis, and use a
      comparative genomic approach to test the hypothesis that this species was
      involved in the hybrid origin of the tropical mitotic parthenogen Meloidogyne
      incognita. Phylogenomic analysis of gene families from M. floridensis, M.
      incognita and an outgroup species Meloidogyne hapla was carried out to trace the
      evolutionary history of these species' genomes, and we demonstrate that M.
      floridensis was one of the parental species in the hybrid origins of M.
      incognita. Analysis of the M. floridensis genome itself revealed many gene loci
      present in divergent copies, as they are in M. incognita, indicating that it too
      had a hybrid origin. The triploid M. incognita is shown to be a complex double
      hybrid between M. floridensis and a third, unidentified, parent. The
      agriculturally important RKN have very complex origins involving the mixing of
      several parental genomes by hybridization and their extreme polyphagy and success
      in agricultural environments may be related to this hybridization, producing
      transgressive variation on which natural selection can act. It is now clear that
      studying RKN variation via individual marker loci may fail due to the species'
      convoluted origins, and multi-species population genomics is essential to
      understand the hybrid diversity and adaptive variation of this important species
      complex. This comparative genomic analysis provides a compelling example of the
      importance and complexity of hybridization in generating animal species diversity
      more generally. 

PMID- 24860697
TI  - Using laser micro-dissection and qRT-PCR to analyze cell type-specific gene
      expression in Norway spruce phloem.
AB  - The tangentially oriented polyphenolic parenchyma (PP) and radially organized ray
      parenchyma in the phloem are central in the defense of conifer stems against
      insects and pathogens. Laser micro-dissection enables examination of cell
      specific defense responses. To examine induced defense responses in Norway spruce
      stems inoculated with the necrotrophic blue-stain fungus Ceratocystis polonica,
      RNA extracted from laser micro-dissected phloem parenchyma and vascular cambium
      was analyzed using real-time RT-PCR (qRT-PCR) to profile transcript levels of
      selected resistance marker genes. The monitored transcripts included three
      pathogenesis-related proteins (class IV chitinase (CHI4), defensin (SPI1),
      peroxidase (PX3), two terpene synthesis related proteins (DXPS and LAS), one
      ethylene biosynthesis related protein (ACS), and a phenylalanine ammonia-lyase
      (PAL). Three days following inoculation, four genes (CHI4, PAL, PX3, SPI1) were
      differentially induced in individual cell and tissue types, both close to the
      inoculation site (5 mm above) and, to a lesser degree, further away (10 mm
      above). These resistance marker genes were all highly induced in ray parenchyma,
      supporting the important role of the rays in spruce defense propagation. CHI4 and
      PAL were also induced in PP cells and in conducting secondary phloem tissues. Our
      data suggests that different cell types in the secondary phloem of Norway spruce
      have overlapping but not fully redundant roles in active host defense.
      Furthermore, the study demonstrates the usefulness of laser micro-dissection
      coupled with qRT-PCR to characterize gene expression in different cell types of
      conifer bark. 

PMID- 24860698
TI  - Modulatory interactions between the default mode network and task positive
      networks in resting-state.
AB  - The two major brain networks, i.e., the default mode network (DMN) and the task
      positive network, typically reveal negative and variable connectivity in resting
      state. In the present study, we examined whether the connectivity between the DMN
      and different components of the task positive network were modulated by other
      brain regions by using physiophysiological interaction (PPI) on resting-state
      functional magnetic resonance imaging data. Spatial independent component
      analysis was first conducted to identify components that represented networks of
      interest, including the anterior and posterior DMNs, salience, dorsal attention,
      left and right executive networks. PPI analysis was conducted between pairs of
      these networks to identify networks or regions that showed modulatory
      interactions with the two networks. Both network-wise and voxel-wise analyses
      revealed reciprocal positive modulatory interactions between the DMN, salience,
      and executive networks. Together with the anatomical properties of the salience
      network regions, the results suggest that the salience network may modulate the
      relationship between the DMN and executive networks. In addition, voxel-wise
      analysis demonstrated that the basal ganglia and thalamus positively interacted
      with the salience network and the dorsal attention network, and negatively
      interacted with the salience network and the DMN. The results demonstrated
      complex modulatory interactions among the DMNs and task positive networks in
      resting-state, and suggested that communications between these networks may be
      modulated by some critical brain structures such as the salience network, basal
      ganglia, and thalamus. 

PMID- 24860699
TI  - Distinct expression patterns of Notch ligands, Dll1 and Dll4, in normal and
      inflamed mice intestine.
AB  - Reports have suggested that the two Notch ligands, Dll1 and Dll4, are
      indispensable to maintain the homeostasis of the intestinal epithelium. However,
      within the intestinal epithelium, the precise distribution of the cells that
      express those ligands at the protein level remains largely unknown. Here, we show
      a series of immunohistochemical analysis through which we successfully identified
      mice intestinal epithelial cells (IECs) that endogenously express Dll1 or Dll4.
      Results showed that Dll1-positive (Dll1+ve) IECs reside exclusively within the
      crypt, whereas Dll4-positive (Dll4+ve) IECs can locate both in the crypt and in
      the villus of the small intestine. Also in the colon, Dll1+ve IECs resided at the
      lower part of the crypt, whereas Dll4+ve IECs resided at both upper and lower
      part of the crypt, including the surface epithelium. Both Dll1+ve and Dll4+ve
      IECs were ATOH1-positive, but Hes1-negative cells, and located adjacent to Hes1
      positive cells within the crypts. A sub-population of both Dll1+ve and Dll4+ve
      IECs appeared to co-express Muc2, but rarely co-expressed other secretory lineage
      markers. However, as compared to Dll1+ve IECs, Dll4+ve IECs included larger
      number of Muc2-postive IECs, suggesting that Dll4 is more preferentially
      expressed by goblet cells. Also, we identified that Dll4 is expressed in the
      Paneth cells of the small intestine, whereas Dll1 and Dll4 is expressed in the c
      kit-positive IECs of the colon, indicating that Dll1+ve and Dll4+ve IECs may
      contribute to constitute the intestinal stem cell niche. Compared to the normal
      colon, analysis of DSS-colitis showed that number of Dll1+ve IECs significantly
      decrease in the elongated crypts of the inflamed colonic mucosa. In sharp
      contrast, number of Dll4+ve IECs showed a significant increase in those crypts,
      which was accompanied by the increase in number of Hes1-positive IECs. Those
      Dll4+ve IECs were mostly found adjacent to the Hes1-positive IECs, suggesting
      that Dll4 may act as a major Notch ligand in the crypts of the inflamed colonic
      mucosa. Our results illustrate distinct expression patterns of Dll1 and Dll4
      within the intestinal epithelium, and suggest that these two ligands may have
      different roles in normal and inflamed mucosa. 

PMID- 24860700
TI  - Heritability estimation of osteoarthritis in the pig-tailed macaque (Macaca
      nemestrina) with a look toward future data collection.
AB  - We examine heritability estimation of an ordinal trait for osteoarthritis, using
      a population of pig-tailed macaques from the Washington National Primate Research
      Center (WaNPRC). This estimation is non-trivial, as the data consist of ordinal
      measurements on 16 intervertebral spaces throughout each macaque's spinal cord,
      with many missing values. We examine the resulting heritability estimates from
      different model choices, and also perform a simulation study to compare the
      performance of heritability estimation with these different models under specific
      known parameter values. Under both the real data analysis and the simulation
      study, we find that heritability estimates from an assumption of normality of the
      trait differ greatly from those of ordered probit regression, which considers the
      ordinality of the trait. This finding indicates that some caution should be
      observed regarding model selection when estimating heritability of an ordinal
      quantity. Furthermore, we find evidence that our real data have little
      information for valid heritability estimation under ordered probit regression. We
      thus conclude with an exploration of sample size requirements for heritability
      estimation under this model. For an ordinal trait, an incorrect assumption of
      normality can lead to severely biased heritability estimation. Sample size
      requirements for heritability estimation of an ordinal trait under the threshold
      model depends on the pedigree structure, trait distribution and the degree of
      relatedness between each phenotyped individual. Our sample of 173 monkeys did not
      have enough information from which to estimate heritability, but estimable
      heritability can be obtained with as few as 180 related individuals under certain
      scenarios examined here. 

PMID- 24860701
TI  - Variable effects of temperature on insect herbivory.
AB  - Rising temperatures can influence the top-down control of plant biomass by
      increasing herbivore metabolic demands. Unfortunately, we know relatively little
      about the effects of temperature on herbivory rates for most insect herbivores in
      a given community. Evolutionary history, adaptation to local environments, and
      dietary factors may lead to variable thermal response curves across different
      species. Here we characterized the effect of temperature on herbivory rates for
      21 herbivore-plant pairs, encompassing 14 herbivore and 12 plant species. We show
      that overall consumption rates increase with temperature between 20 and 30 
      degrees C but do not increase further with increasing temperature. However, there
      is substantial variation in thermal responses among individual herbivore-plant
      pairs at the highest temperatures. Over one third of the herbivore-plant pairs
      showed declining consumption rates at high temperatures, while an approximately
      equal number showed increasing consumption rates. Such variation existed even
      within herbivore species, as some species exhibited idiosyncratic thermal
      response curves on different host plants. Thus, rising temperatures, particularly
      with respect to climate change, may have highly variable effects on plant
      herbivore interactions and, ultimately, top-down control of plant biomass. 

PMID- 24860703
TI  - Linking a genetic defect in migraine to spreading depression in a computational
      model.
AB  - Familial hemiplegic migraine (FHM) is a rare subtype of migraine with aura. A
      mutation causing FHM type 3 (FHM3) has been identified in SCN1A encoding the
      Nav1.1 Na(+) channel. This genetic defect affects the inactivation gate. While
      the Na(+) tail currents following voltage steps are consistent with both
      hyperexcitability and hypoexcitability, in this computational study, we
      investigate functional consequences beyond these isolated events. Our extended
      Hodgkin-Huxley framework establishes a connection between genotype and cellular
      phenotype, i.e., the pathophysiological dynamics that spans over multiple time
      scales and is relevant to migraine with aura. In particular, we investigate the
      dynamical repertoire from normal spiking (milliseconds) to spreading depression
      and anoxic depolarization (tens of seconds) and show that FHM3 mutations render
      gray matter tissue more vulnerable to spreading depression despite opposing
      effects associated with action potential generation. We conclude that the
      classification in terms of hypoexcitability vs. hyperexcitability is too simple a
      scheme. Our mathematical analysis provides further basic insight into also
      previously discussed criticisms against this scheme based on psychophysical and
      clinical data. 

PMID- 24860702
TI  - Comparison of histomorphology and DNA preservation produced by fixatives in the
      veterinary diagnostic laboratory setting.
AB  - Histopathology is the most useful tool for diagnosis of a number of diseases,
      especially cancer. To be effective, histopathology requires that tissues be fixed
      prior to processing. Formalin is currently the most common histologic fixative,
      offering many advantages: it is cheap, readily available, and pathologists are
      routinely trained to examine tissues fixed in formalin. However, formalin
      fixation substantially degrades tissue DNA, hindering subsequent use in
      diagnostics and research. We therefore evaluated three alternative fixatives,
      TissueTek((r)) Xpress((r)) Molecular Fixative, modified methacarn, and
      PAXgene((r)), all of which have been proposed as formalin alternatives, to
      determine their suitability for routine use in a veterinary diagnostic
      laboratory. This was accomplished by examining the histomorphology of sections
      produced from fixed tissues as well as the ability to amplify fragments from
      extracted DNA. Tissues were sampled from two dogs and four cats, fixed for 24-48
      h, and processed routinely. While all fixatives produced acceptable
      histomorphology, formalin had significantly better morphologic characteristics
      than the other three fixatives. Alternative fixatives generally had better DNA
      amplification than formalin, although results varied somewhat depending on the
      tissue examined. While no fixative is yet ready to replace formalin, the
      alternative fixatives examined may be useful as adjuncts to formalin in
      diagnostic practices. 

PMID- 24860704
TI  - Characterisation of the horse transcriptome from immunologically active tissues.
AB  - The immune system of the horse has not been well studied, despite the fact that
      the horse displays several features such as sensitivity to bacterial
      lipopolysaccharide that make them in many ways a more suitable model of some
      human disorders than the current rodent models. The difficulty of working with
      large animal models has however limited characterisation of gene expression in
      the horse immune system with current annotations for the equine genome restricted
      to predictions from other mammals and the few described horse proteins. This
      paper outlines sequencing of 184 million transcriptome short reads from
      immunologically active tissues of three horses including the genome reference
      "Twilight". In a comparison with the Ensembl horse genome annotation, we found
      8,763 potentially novel isoforms. 

PMID- 24860706
TI  - The Familial Union between Caregivers and the Juvenile Justice System.

PMID- 24860705
TI  - Mutation analysis of the SLC26A4, FOXI1 and KCNJ10 genes in individuals with
      congenital hearing loss.
AB  - Pendred syndrome (PDS) and DFNB4 comprise a phenotypic spectrum of sensorineural
      hearing loss disorders that typically result from biallelic mutations of the
      SLC26A4 gene. Although PDS and DFNB4 are recessively inherited, sequencing of the
      coding regions and splice sites of SLC26A4 in individuals suspected to be
      affected with these conditions often fails to identify two mutations. We
      investigated the potential contribution of large SLC26A4 deletions and
      duplications to sensorineural hearing loss (SNHL) by screening 107 probands with
      one known SLC26A4 mutation by Multiplex Ligation-dependent Probe Amplification
      (MLPA). A heterozygous deletion, spanning exons 4-6, was detected in only one
      individual, accounting for approximately 1% of the missing mutations in our
      cohort. This low frequency is consistent with previously published MLPA results.
      We also examined the potential involvement of digenic inheritance in PDS/DFNB4 by
      sequencing the coding regions of FOXI1 and KCNJ10. Of the 29 probands who were
      sequenced, three carried nonsynonymous variants including one novel sequence
      change in FOXI1 and two polymorphisms in KCNJ10. We performed a review of prior
      studies and, in conjunction with our current data, conclude that the frequency of
      FOXI1 (1.4%) and KCNJ10 (3.6%) variants in PDS/DFNB4 individuals is low. Our
      results, in combination with previously published reports, indicate that large
      SLC26A4 deletions and duplications as well as mutations of FOXI1 and KCNJ10 play
      limited roles in the pathogenesis of SNHL and suggest that other genetic factors
      likely contribute to the phenotype. 

PMID- 24860707
TI  - Tandem mass spectrometry of nitric oxide and hydrogen sulfide releasing aspirins:
      a hint into activity behavior.
AB  - Aspirin (acetylsalicylic acid, ASA) is the most popular non-steroidal anti
      inflammatory drug. However, due to its action on cyclooxygenase and its acid
      nature, aspirin is associated with adverse gastrointestinal effects. In an effort
      to minimize these side effects, NO-donor and H2S-donor ASA co-drugs have been
      designed and tested. Their mass spectrometric behavior is now analyzed and
      reported. Positive ions were obtained by electrospray ionization involving
      protonation or alkali metal attachment. Their dissociation processes have been
      studied by collision induced dissociation in a triple quadrupole instrument. High
      mass accuracy measurements have been recorded on a Fourier transform ion
      cyclotron resonance mass spectrometer. The protonated molecules dissociate by an
      exclusive or largely prevailing path leading to acetyloxy-substituted benzoyl
      cation, namely an ASA unit. The process is reminiscent of the enzymatic
      hydrolysis, releasing intact ASA to a large extent. Only at higher collision
      energy does the formal ketene loss disrupt the ASA moiety. The gas phase
      chemistry of protonated ASA-releasing drugs develops along elementary
      dissociation steps analogous to the reactive processes in complex biological
      environments. This notion may provide a tool for preliminary testing of new
      compounds. 

PMID- 24860708
TI  - Metabolic profiling of oxidized lipid-derived volatiles in blood by gas
      chromatography/mass spectrometry with in-tube extraction.
AB  - Once lipids are oxidized, various volatiles are produced by cleavage of the fatty
      acid side chain. Considering the variety of lipids present in the body, a large
      number of possible volatiles might originate from oxidized lipids. However, only
      specific volatiles such as aldehydes are exclusively examined in current studies,
      and there is no reported method for the exhaustive analysis of all volatiles. We
      developed a sensitive analytical method for the detection of all possible
      volatiles for multimarker profiling, applying a new extraction method called in
      tube extraction. Oxidized phosphatidyl choline standards were prepared in vitro
      and analyzed in order to determine the potential variety of volatiles. Over 40
      compounds, including alcohols, ketones, and furanones, were identified in
      addition to the aldehydes reported previously. Based on this result, we applied
      our analytical method to mouse plasma and identified 12 volatiles, including 1
      octen-3-ol, which is correlated to disease states. To determine the volatile
      profile after oxidation, we oxidized plasma in vitro under various conditions and
      identified 27 volatiles, including 1-octen-3-ol and benzaldehyde. The generation
      capacity of each volatile was different. This method allows sensitive and
      exhaustive analysis of various volatiles in addition to aldehydes. 

PMID- 24860710
TI  - Collision-Induced Dissociation Study of the Adduct Ions Produced in NO3 (-)-Free
      Area of Atmospheric Pressure Negative Corona Discharges under Ambient Air
      Conditions.
AB  - Collision-induced dissociation (CID) experiments of adducts [M+R](-) with
      negative atmospheric ions R(-) (O2 (-), HCO3 (-) and COO(-)(COOH)) produced in
      NO3 (-)-free discharge area in atmospheric pressure corona discharge ionization
      (APCDI) method were performed using aliphatic and aromatic compounds M. The
      [M+R](-) adducts for individual R(-) fragmented to form deprotonated analytes [M
      H](-) as well as the specific product ions which also occurred in the CID of [M
      H](-), independent of analytes with several different functional groups. The
      results obtained suggested that the specific product ions formed in the CID of
      [M+R](-), as well as CID of [M-H](-), are generated due to further fragmentation
      of the product ions [M-H](-). It was concluded, therefore, that CID of [M+R](-)
      formed in NO3 (-)-free discharge area can indirectly lead to the formation of the
      product ions originating from [M-H](-). 

PMID- 24860709
TI  - 5-nitrosalicylic Acid as a novel matrix for in-source decay in matrix-assisted
      laser desorption/ionization mass spectrometry.
AB  - The matrix-assisted laser desorption/ionization in-source decay (MALDI-ISD) of
      peptides and glycans was studied using an oxidizing chemical, 5-nitrosalicylic
      acid (5-NSA) as the matrix. The use of 5-NSA for the MALDI-ISD of peptides and
      glycans promoted fragmentation pathways involving "hydrogen-deficient" radical
      precursors. Hydrogen abstraction from peptides resulted in the production of a
      "hydrogen-deficient" peptide radical that contained a radical site on the amide
      nitrogen in the peptide backbone with subsequent radical-induced cleavage at the
      Calpha-C bonds. Cleavage at the Calpha-C bond leads to the production of an a
      (*)/x fragment pair and the radical a (*) ions then undergo further hydrogen
      abstraction to form a ions after Calpha-C bond cleavage. Since the Pro residue
      does not contain a nitrogen-centered radical site, Calpha-C bond cleavage does
      not occur at this site. Alternatively, the specific cleavage of CO-N bonds leads
      to a b (*)/y fragment pair at Xxx-Pro which occurs via hydrogen abstraction from
      the Calpha-H in the Pro residue. In contrast, "hydrogen-deficient" glycan
      radicals were generated by hydrogen abstraction from hydroxyl groups in glycans.
      Both glycosidic and cross-ring cleavages occurred as the result of the
      degradation of "hydrogen-deficient" glycan radicals. Cross-ring cleavage ions are
      potentially useful in linkage analysis, one of the most critical steps in the
      characterization of glycans. Moreover, isobaric glycans could be distinguished by
      structure specific ISD ions, and the molar ratio of glycan isomers in a mixture
      can be estimated from their fragment ions abundance ratios. MALDI-ISD with 5-NSA
      could be a useful method for the sequencing of peptides including the location of
      post-translational modifications, identification and semi-quantitative analysis
      of mixtures of glycan isomers. 

PMID- 24860711
TI  - Quantification of Candesartan in Mouse Plasma by MALDI-TOFMS and in Tissue
      Sections by MALDI-Imaging Using the Stable-Isotope Dilution Technique.
AB  - To determine the contents of candesartan in mouse plasma, and blood vessel and
      kidney sliced sections and also better understand its pharmacokinetics, we
      applied matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry (MALDI-TOFMS) and MALDI-imaging mass spectrometry (IMS) with the
      selected reaction monitoring (SRM) mode using a labeled-internal standard. The
      results of fundamental examinations showed that the slope of the resulting curves
      of candesartan in the plasma from the equation was 0.91 and the y-intercept was
      0.02. Both intra- and inter-day accuracies (n=10) and the precision of
      candesartan in the plasma by MALDI-TOFMS with the SRM mode were in the range of
      3.4 to 17.3% and 93.2%, respectively. The detection limit of candesartan in
      spiked plasma was 0.2 nmol/L. IMS analysis enabled us to clarify distinct spacial
      time-distribution images in sliced mouse blood vessel and kidney sections
      although it still needed to improve a protocol of quantification. Typical
      pharmacokinetic patterns of candesartan were obtained in the plasma and sliced
      kidney sections, but those in the blood vessel sections gradually increased 24 h
      after administration. MALDI-TOFMS and IMS with the SRM mode are powerful tools to
      identify the spacial distribution and traceability of candesartan in sliced blood
      vessel and tissue sections as well as in the plasma. 

PMID- 24860712
TI  - A Novel Derivatization Reagent in the Determination of the Number of OH End
      Groups in Poly(ethylene glycol) by Matrix-Assisted Laser Desorption/Ionization
      Mass Spectrometry.
AB  - The potential of a novel derivatization reagent, trifluoroacetic anhydride
      (TFAA), in determining the number of OH groups in poly(ethylene glycol) (PEG) was
      investigated by matrix-assisted laser desorption/ionization mass spectrometry
      (MALDI-MS). The MALDI mass spectra of the products revealed peaks of sodiated
      derivative cations, whose shift by the respective increments, Deltam/z: 96 *
      number of OH, allowed for the determination of the number of end functional
      groups with active hydrogens. In the present study, complete acylation of OH
      groups by TFAA proceeded rapidly, and only required mixing in acetonitrile
      solvent without purification. As a result, the number of OH end groups of PEG
      could be determined rapidly. 

PMID- 24860713
TI  - Peptide Profiling Using Matrix-Assisted Laser Desorption/Ionization-Time-of
      Flight Mass Spectrometry for Identification of Animal Fibers.
AB  - Identification of fibers for verification of their specific animal origin is
      necessary for maintaining quality and value in the clothing industry. In order to
      examine adulteration in animal fibers, there is a commercially accepted method of
      microscopy analysis. However, this method is subjective and time-consuming due to
      its reliance on an operator identifying magnified fibers from their scale image
      and other features. Therefore, alternative reliable identification methods are
      required. In this study, peptide analysis using matrix-assisted laser
      desorption/ionization-time-of-flight mass spectrometry (MALDI-TOFMS) is presented
      and used to distinguish between cashmere, wool, mohair, yak, camel, angora, and
      alpaca in untreated and treated fibers (dyed, chlorinated wool). Typical m/z
      values for each specific type of animal fiber were identified. Predictive models
      that could identify seven types of animal fibers as well as 50% blended samples
      were successfully constructed using multivariate analyses such as PCA and PLS
      regression. This technique is therefore extremely useful for complementing the
      conventional tests for detecting adulteration in animal fiber fabrics and
      clothing. 

PMID- 24860714
TI  - Differential (14)N/(15)N-Labeling of Peptides Using N-Terminal Charge
      Derivatization with a High-Proton Affinity for Straightforward de novo Peptide
      Sequencing.
AB  - While de novo peptide sequencing is essential in many situations, it remains a
      difficult task. This is because peptide fragmentation results in complicated and
      often incomplete product ion spectra. In a previous study, we demonstrated that N
      terminal charge derivatization with 4-amidinobenzoic acid (Aba) resulted in
      improved peptide fragmentation under low-energy CID conditions. However, even
      with this derivatization, some ambiguity exists, due to difficulties in
      discriminating between N- and C-terminal fragments. In this study, to
      specifically identify b-ions from complex product ion spectra, the differential
      (14)N/(15)N-labeling of peptides was performed using Aba derivatization. (15)N
      Labeled Aba was synthesized in the form of a succinimide ester. Peptides were
      derivatized individually with (14)N-Aba or (15)N-Aba and analyzed by ESI-MS/MS
      using a linear ion trap-Orbitrap hybrid FTMS system. The N-terminal fragments
      (i.e., b-ions) were then identified based on m/z differences arising from isotope
      labeling. By comparing the spectra between (14)N- and (15)N-Aba derivatized
      peptides, b-ions could be successfully identified based on the m/z shifts, which
      provided reliable sequencing results for all of the peptides examined in this
      study. The method developed in this study allows the easy and reliable de novo
      sequencing of peptides, which is useful in peptidomics and proteomics studies. 

PMID- 24860715
TI  - Laser Desorption/Ionization Mass Spectrometry (LDI-MS) of Lipids with Iron Oxide
      Nanoparticle-Coated Targets.
AB  - Iron oxide nanoparticle (NP)-coated target plates were employed for the direct
      detection and analysis of low molecular weight lipids by laser
      desorption/ionization (LDI) mass spectrometry (MS). We have demonstrated that the
      use of the iron oxide NP-coated target provides a simple, direct, and rapid
      detection method for lipid standards and epidermal surface lipids without any
      cumbersome sample pretreatment as well as mass spectra that are free of
      background matrix peaks. Lipid standards (1-stearoyl-sn-glycero-3-phosphocholine,
      1,2-dioleoyl-sn-glycerol, 1-palmitoyl-2-oleoyl-3-linoleoyl-rac-glycerol, 1,2
      distearoyl-sn-glycero-3-phosphocholine) were detected as either protonated or
      cationated species. Clean MS/MS spectra for each lipid were also successfully
      obtained. Pre-MS surface cleaning of the target plates with UV-ozone treatment
      successfully removed organic contaminants that would interfere with the mass
      spectra especially in the low molecular weight region. Preliminary application of
      the presented target plate to the detection of endogenous lipids in latent
      fingerprints showed promising results and for potential use in the visualization
      and chemical composition determination of latent fingerprints by nanoparticle
      assistance. 

PMID- 24860716
TI  - Migrant and minority family members in the intensive care unit. A review of the
      literature.
AB  - Statistics show that people with migrant and minority background as patients are
      significant in numbers in the intensive care unit. This also puts family members
      in the perspective of nursing because family members are an inherent part of the
      intensive care unit. Family-centered care is perhaps most applicable to
      vulnerable populations like migrant family in the intensive care unit to meet
      family member's needs. But very little is known about the situation of migrant
      and minority family members in the intensive care unit. The aim of the study was
      to explore the state of the science regarding family-centered care in the
      intensive care unit of patients with migration background in general and with a
      possible focus on major migrant populations in Austria-Former Yugoslavian und
      Turkish origin. A literature review investigated research articles that contained
      information on migrant and minority family members in the intensive care unit.
      Key points in the relevant articles were identified and categorized into themes
      with an explanation of findings at the end. Seventeen articles fulfilled the
      inclusion criteria. No article was found regarding groups of major migrant
      population groups in Austria. The included articles uncovered five predominant
      themes: importance of cultural norms, communication, family dynamics, universal
      caring, and nursing/provider deficit in culturally competent care. In order to
      provide adequate nursing care a more cohesive body of information on more
      specific geographic and cultural populations is recommended. Because of the
      complete lack of research regarding migrant families of Former Yugoslavian and
      Turkish origin into Austria, an exploration of this population is recommended.

PMID- 24860717
TI  - High resolution seismic data coupled to Multibeam bathymetry of Stromboli island
      collected in the frame of the Stromboli geophysical experiment: implications with
      the marine geophysics and volcanology of the Aeolian Arc volcanic complex
      (Sicily, Southern Tyrrhenian sea, Italy).
AB  - New high resolution seismic data (Subbottom Chirp) coupled to high resolution
      Multibeam bathymetry collected in the frame of the Stromboli geophysical
      experiment aimed at recording active seismic data and tomography of the Stromboli
      Island are here presented. The Stromboli geophysical experiment has been already
      carried out based on onshore and offshore data acquisition in order to
      investigate the deep structure and the location of the magma chambers of the
      Stromboli volcano. A new detailed swath bathymetry of Stromboli Island is here
      shown and discussed to reconstruct an up-to-date morpho-bathymetry and marine
      geology of the area compared to the volcanologic setting of the Aeolian Arc
      volcanic complex. Due to its high resolution the new Digital Terrain Model of the
      Stromboli Island gives interesting information about the submerged structure of
      the volcano, particularly about the volcano-tectonic and gravitational processes
      involving the submarine flanks of the edifice. Several seismic units have been
      identified based on the geologic interpretation of Subbottom Chirp profiles
      recorded around the volcanic edifice and interpreted as volcanic acoustic
      basement pertaining to the volcano and overlying slide chaotic bodies emplaced
      during its complex volcano-tectonic evolution. They are related to the eruptive
      activity of Stromboli, mainly poliphasic and to regional geological processes
      involving the intriguing geology of the Aeolian Arc, a volcanic area still in
      activity and needing improved research interest. 

PMID- 24860718
TI  - Cardiac safety results from a phase II, open-label, multicenter, pilot study of
      two docetaxel-based regimens plus bevacizumab for the adjuvant treatment of
      subjects with node-positive or high-risk node-negative breast cancer.
AB  - PURPOSE: Adding antiangiogenic therapy to standard chemotherapy has improved
      response rates and progression-free survival in metastatic breast cancer (BC)
      patients. This phase II study evaluated cardiac safety of bevacizumab
      with/without trastuzumab with two docetaxel-based regimens in early BC. METHODS:
      127 women with non-metastatic node-positive or high-risk node-negative BC were
      enrolled. Women with human epidermal growth factor receptor 2 (HER2)-negative BC
      (n = 93) received docetaxel/doxorubicin/cyclophosphamide (TAC) + bevacizumab,
      while women with HER2-positive disease (n = 34) received
      docetaxel/carboplatin/trastuzumab (TCH) + bevacizumab, every 3 weeks for six
      cycles. Maintenance therapy with bevacizumab alone or bevacizumab plus
      trastuzumab, respectively, was given every 3 weeks for 52 weeks. The primary
      objective was to evaluate cardiac safety, as measured by the incidence of >=
      grade 3 clinical congestive heart failure (CHF); the secondary objective was
      assessment of safety and toxicity. RESULTS: At least one cardiac adverse event
      (AE; CHF, cardiomyopathy, or left ventricular dysfunction) was reported in 26.1%
      of TAC (n = 92) and 17.6% of TCH subjects (n = 34); there were no cardiac deaths.
      >= Grade 3 clinical CHF was observed in 4.3% in the TAC plus bevacizumab stratum
      and 0% in the TCH plus bevacizumab stratum. A >= grade 3 treatment-emergent AE
      (any kind) related to study treatment was observed in 59.8% in the TAC with
      bevacizumab and 52.9% in the TCH plus bevacizumab stratum. CONCLUSION: Adding
      bevacizumab to a docetaxel-based regimen with trastuzumab did not appear to
      increase cardiotoxicity. TRIAL REGISTRATION: ClinicalTrials.gov Identifier:
      NCT00446030, registered March 8, 2007.

PMID- 24860719
TI  - Histoplasmosis in HIV-Infected Patients: A Review of New Developments and
      Remaining Gaps.
AB  - Histoplasma capsulatum is responsible for histoplasmosis, a fungal disease with
      worldwide distribution that can affect both immunocompromised and imunocompetent
      individuals. During the highly active antiretroviral therapy (HAART) era,
      morbidity and mortality due to histoplasmosis remained a public heatlh problem in
      low-income and high-income countries. The true burden of HIV-associated
      histoplasmosis is either not fully known or neglected since it is not a
      notifiable disease. Progress has been made in DNA patterns of strains and
      understanding of pathogenesis, and hopefully these will help identify new
      therapeutic targets. Unfortunately, histoplasmosis is still widely mistaken for
      multidrug-resistant tuberculosis, leading to numerous avoidable deaths, even if
      they are easily distinguishable. The new diagnostic tools and therapeutics
      developments have still not been made available in most endemic regions. Still,
      recent developments are promising because of their good clinical characteristics
      and also because they will be commercially available and affordable. This review
      of published data and gaps may help define and guide future research.

PMID- 24860720
TI  - Allergen Peptides, Recombinant Allergens and Hypoallergens for Allergen-Specific
      Immunotherapy.
AB  - Allergic diseases are among the most common health issues worldwide. Specific
      immunotherapy has remained the only disease-modifying treatment, but it is not
      effective in all patients and may cause side effects. Over the last 25 years,
      allergen molecules from most prevalent allergen sources have been isolated and
      produced as recombinant proteins. Not only are these molecules useful in improved
      allergy diagnosis, but they also have the potential to revolutionize the
      treatment of allergic disease by means of immunotherapy. Panels of unmodified
      recombinant allergens have already been shown to effectively replace natural
      allergen extracts in therapy. Through genetic engineering, several molecules have
      been designed with modified immunological properties. Hypoallergens have been
      produced that have reduced IgE binding capacity but retained T cell reactivity
      and T cell peptides which stimulate allergen-specific T cells, and these have
      already been investigated in clinical trials. New vaccines have been recently
      created with both reduced IgE and T cell reactivity but retained ability to
      induce protective allergen-specific IgG antibodies. The latter approach works by
      fusing per se non-IgE reactive peptides derived from IgE binding sites of the
      allergens to a virus protein, which acts as a carrier and provides the T-cell
      help necessary for immune stimulation and protective antibody production. In this
      review, we will highlight the different novel approaches for immunotherapy and
      will report on prior and ongoing clinical studies.

PMID- 24860721
TI  - Arsenic-Associated Changes to the Epigenome: What Are the Functional
      Consequences?
AB  - Inorganic arsenic (iAs) poses a major threat to worldwide human health, and yet
      the molecular mechanisms underlying the toxic effects associated with iAs
      exposure are not well understood. There is increasing experimental evidence
      indicating that epigenetic modifications may play a major role in the development
      of diseases associated with exposure to environmental toxicants. Research in the
      field has firmly established that iAs exposure is associated with epigenetic
      alterations including changes in DNA methylation, miRNA abundance, and post
      translational histone modifications. Here, we summarize recent studies that have
      expanded the current knowledge of these relationships. These studies have
      pinpointed specific regions of the genome and genes that are targets of arsenical
      induced epigenetic changes, including those associated with in utero iAs
      exposure. The recent literature indicates that iAs biotransformation likely plays
      an important role in the relationship between iAs exposure and the epigenome, in
      addition to the sex and genetic background of individuals. The research also
      shows that relatively low to moderate exposure to iAs is associated with
      epigenetic effects. However, while it is well established that arsenicals can
      alter components of the epigenome, in many cases, the biological significance of
      these alterations remains unknown. The manner by which these and future studies
      may help inform the role of epigenetic modifications in the development of iAs
      associated disease is evaluated and the need for functional validation
      emphasized.

PMID- 24860723
TI  - Hydroxymethylation as a Novel Environmental Biosensor.
AB  - Beyond the genome, epigenetics has become a promising approach in understanding
      the interactions between the gene and the environment. Epigenetic regulation
      includes DNA methylation, histone modifications, and non-coding RNAs. Among
      these, DNA methylation, which is the addition of a methyl group to the fifth base
      of cytosine to produce 5-methylcytosine (5-mC), is most commonly studied.
      Epigenetic regulation has changed given the discovery of 5-hydroxymethylcytosine
      (5-hmC), considered the "sixth base", and the nature of TET proteins to catalyze
      5-mC oxidation to 5-hmC. 5-hydroxymethylation has been proposed to be a stable
      intermediate between methylation and demethylation and has raised questions about
      the functions of 5-hmC in gene regulation in cells, tissues, and organs in
      response to environmental exposure. Herein, we have provided an introduction to
      the chemistry of 5-hydroxymethylation, and the techniques for detection of 5
      hydroxymethylation. In addition, we have reviewed current reports describing how
      5-hmC responds to environmental factors, leading to the development of disease.
      And finally, we have discussed the potential use of 5-hmC in the study of disease
      development. All in all, it is our goal to provide innovative and convincing
      epigenetic studies for understanding the etiology of environmentally-related
      human disease, and translate these epigenetic findings into lifestyle
      recommendations and clinical practices to prevent and cure disease.

PMID- 24860722
TI  - The Effects of Arsenic Exposure on Neurological and Cognitive Dysfunction in
      Human and Rodent Studies: A Review.
AB  - Arsenic toxicity is a worldwide health concern as several millions of people are
      exposed to this toxicant via drinking water, and exposure affects almost every
      organ system in the body including the brain. Recent studies have shown that even
      low concentrations of arsenic impair neurological function, particularly in
      children. This review will focus on the current epidemiological evidence of
      arsenic neurotoxicity in children and adults, with emphasis on cognitive
      dysfunction, including learning and memory deficits and mood disorders. We
      provide a cohesive synthesis of the animal studies that have focused on neural
      mechanisms of dysfunction after arsenic exposure including altered epigenetics;
      hippocampal function; glucocorticoid and hypothalamus-pituitary-adrenal axis
      (HPA) pathway signaling; glutamatergic, cholinergic and monoaminergic signaling;
      adult neurogenesis; and increased Alzheimer's-associated pathologies. Finally, we
      briefly discuss new studies focusing on therapeutic strategies to combat arsenic
      toxicity including the use of selenium and zinc.

PMID- 24860724
TI  - Intelligent recognitive systems in nanomedicine.
AB  - There is a bright future in the development and utilization of nanoscale systems
      based on intelligent materials that can respond to external input providing a
      beneficial function. Specific functional groups can be incorporated into polymers
      to make them responsive to environmental stimuli such as pH, temperature, or
      varying concentrations of biomolecules. The fusion of such "intelligent"
      biomaterials with nanotechnology has led to the development of powerful
      therapeutic and diagnostic platforms. For example, targeted release of proteins
      and chemotherapeutic drugs has been achieved using pH-responsive nanocarriers
      while biosensors with ultra-trace detection limits are being made using
      nanoscale, molecularly imprinted polymers. The efficacy of therapeutics and the
      sensitivity of diagnostic platforms will continue to progress as unique
      combinations of responsive polymers and nanomaterials emerge.

PMID- 24860725
TI  - Hoarding behavior among young children with obsessive-compulsive disorder.
AB  - Previous research has shown that among the various subtypes of obsessive
      compulsive disorder (OCD), adults (e.g. Frost, Krause & Steketee, 1996) and older
      children and adolescents (Bloch et al., 2009; Storch et al., 2007) with
      problematic hoarding have distinct features and a poor treatment prognosis.
      However, there is limited information on the phenomenology and prevalence of
      hoarding behaviors in young children. The present study characterizes children
      ages 10 and under who present with OCD and hoarding behaviors. Sixty-eight
      children received a structured interview-determined diagnosis of OCD. Clinician
      administered, parent-report, and child-report measures on demographic,
      symptomatic, and diagnostic variables were completed. Clinician ratings of
      hoarding symptoms and parent and child endorsement of the hoarding item on the CY
      BOCS checklist (Scahill, Riddle, McSwiggin-Hardin, & Ort, 1997) determined
      inclusion in the hoarding group (n=33). Compared to children without hoarding
      symptoms (n=35), the presence of hoarding symptoms was associated with an earlier
      age of primary diagnosis onset and a higher proportion of ADHD and provisional
      anxiety diagnoses. These results are partially consistent with the adult
      literature and with findings in older children (Storch et al., 2007). Additional
      data on clinical presentation and phenomenology of hoarding are needed to form a
      developmentally appropriate definition of the behavior.

PMID- 24860726
TI  - Attention to Learning of School Subjects.
AB  - In this brief comment we add to our previous discussion (Posner, Rothbart & Tang,
      2013) of the importance of control mechanisms related to attention networks by
      dealing with how control influences what is learned and how wide the
      generalization of the learned information will be. A brain network connecting the
      anterior cingulate to the hippocampus appears to be important for the
      registration of new learning. This network provides a mechanism for how attention
      influences learning. Information coming to mind spontaneously or during testing
      activates a parietal area related to orienting of attention. Information about
      attentional control systems related to learning holds promise for new
      applications to acquiring expertise related to all school subjects.

PMID- 24860728
TI  - Dietary botanicals for chemoprevention of prostate cancer.

PMID- 24860727
TI  - Combining Hydrophilic Interaction Chromatography (HILIC) and Isotope Tagging for
      Off-Line LC-NMR Applications in Metabolite Analysis.
AB  - The complementary use of liquid chromatography (LC) and nuclear magnetic
      resonance (NMR) has shown high utility in a variety of fields. While the
      significant benefit of spectral simplification can be achieved for the analysis
      of complex samples, other limitations remain. For example, (1)H LC-NMR suffers
      from pH dependent chemical shift variations, especially during urine analysis,
      owing to the high physiological variation of urine pH. Additionally, large
      solvent signals from the mobile phase in LC can obscure lower intensity signals
      and severely limit the number of metabolites detected. These limitations, along
      with sample dilution, hinder the ability to make reliable chemical shift
      assignments. Recently, stable isotopic labeling has been used to detect
      quantitatively specific classes of metabolites of interest in biofluids. Here we
      present a strategy that explores the combined use of two-dimensional hydrophilic
      interaction chromatography (HILIC) and isotope tagged NMR for the unambiguous
      identification of carboxyl containing metabolites present in human urine. The
      ability to separate structurally related compounds chromatographically, in off
      line mode, followed by detection using (1)H-(15)N 2D HSQC (two-dimensional
      heteronuclear single quantum coherence) spectroscopy, resulted in the assignment
      of low concentration carboxyl-containing metabolites from a library of isotope
      labeled compounds. The quantitative nature of this strategy is also demonstrated.

PMID- 24860729
TI  - Chinese traditional medicine and adult neurogenesis in the hippocampus.
AB  - Adult neurogenesis is an important therapeutic target in treating neurological
      disorders. Adult neurogenesis takes place in two regions of the brain:
      Subventricular zone and dentate gyrus in the hippocampus. The progressive
      understanding on hippocampal neurogenesis in aging and mood disorders increases
      the demand to explore powerful and subtle interventions on hippocampal
      neurogenesis. Traditional Chinese herbal medicine provides an abundant
      pharmaceutical platform for modulating hippocampal neurogenesis. Recent progress
      in exploring the effects of Chinese herbal medicine and the related mechanisms
      opens a new direction for regeneration therapy. The current review gives a
      thorough summary of the research progress made in traditional Chinese herbal
      formulas, and the effective compounds in Chinese herbs which are beneficial on
      hippocampal neurogenesis and the possible mechanisms involved. 

PMID- 24860730
TI  - Chemistry, Pharmacology, and Medicinal Property of Sage (Salvia) to Prevent and
      Cure Illnesses such as Obesity, Diabetes, Depression, Dementia, Lupus, Autism,
      Heart Disease, and Cancer.
AB  - For a long time, sage (Salvia) species have been used in traditional medicine for
      the relief of pain, protecting the body against oxidative stress, free radical
      damages, angiogenesis, inflammation, bacterial and virus infection, etc., Several
      studies suggest that sage species can be considered for drug development because
      of their reported pharmacology and therapeutic activities in many countries of
      Asia and Middle East, especially China and India. These studies suggest that
      Salvia species, in addition to treating minor common illnesses, might potentially
      provide novel natural treatments for the relief or cure of many serious and life
      threatening diseases such as depression, dementia, obesity, diabetes, lupus,
      heart disease, and cancer. This article presents a comprehensive analysis of the
      botanical, chemical, and pharmacological aspects of sage (Saliva). 

PMID- 24860731
TI  - Omega-3 Fatty acids could alleviate the risks of traumatic brain injury - a mini
      review.
AB  - Traumatic brain injury (TBI) is an acquired brain trauma that occurs when any
      sudden trauma/injury causes damage to the brain. TBI is characterized by tissue
      damage and imbalance in the cerebral blood flow and metabolism. It has been
      established through laboratory experiments that the dietary supplementation of
      omega-3 fatty acids (FAs) could reduce the oxidative stress developed in brain
      due to TBI. The inclusion of omega-3 FA in diet could normalize the levels of
      brain-derived neurotrophic factor (BDNF), and thus, it could restore the survival
      of neuronal cells. BDNF improves the synaptic transmission by regulating synapsin
      1 and cyclic adenosine monophosphate (cAMP) response element binding protein. The
      brain tissue analysis of TBI models supplemented with omega-3 polyunsaturated
      fatty acids (PUFAs) showed significantly reduced lipid peroxidation, nucleic acid
      and protein oxidation, thereby promoting neuronal and glial cell survival. Thus,
      omega-3 FA intake could be considered as a therapeutic option to reduce the
      secondary neuronal damages initiated by TBI. 

PMID- 24860732
TI  - Anti-inflammatory and Antimicrobial Effects of Heat-Clearing Chinese Herbs: A
      Current Review.
AB  - Inflammation is a normal immune response; but if the body's regulation of
      inflammation is dysfunctional, then it will have an adverse effect on the body.
      Although use of modern drugs for inflammation has a relieving effect, it is still
      unsatisfactory. Moreover, the emergence of drug-resistant strains and even new
      kinds of microorganisms is causing significant morbidity and mortality. Recently,
      more attention has been focused on herbal medicine to treat various diseases
      because of the ability of the herbs to affect multiple target signaling pathways
      and their multiple mechanisms of action. Thus, a large number of studies have
      reported on the anti-inflammatory and antimicrobial effects of the traditional
      Chinese herbs. Literature survey was performed by conducting systematic
      electronic search in PubMed, Science Direct, Google Scholar, and in books. This
      review has listed 11 heat-clearing Chinese herbs (HCCHs) including Scutellaria
      baicalensis ( Huang Qin), Coptis chinensis ( Huang Lian), Flos Lonicerae ( Jin
      Yin Hua), Forsythia suspensa ( Lian Qiao), Isatidis Folium ( Da Qin Ye), Radix
      Isatidis ( Ban Lan Gen), Viola yedoensis ( Zi Hua Di Din), Pulsatilla Radix ( Bai
      Tou Wen), Andrographis paniculata ( Chuan Xin Lian), Houttuynia cordata ( Yu Xing
      Cao), and Patrinia Herba ( Bai Jian Cao), which have anti-inflammatory and
      antimicrobial effects, and has described their effects through different
      mechanisms of action and multiple targets. Their ability to affect multiple
      target signaling pathways and their potential mechanisms of action contributing
      to their anti-inflammatory and antimicrobial activity may be related to their
      action of removing heat and counteracting toxicity. Further studies are needed on
      the collection of HCCHs to know the detailed mechanism of action of herbs in this
      group for the assessment of effective drug. 

PMID- 24860733
TI  - An integrated mind-body approach to arthritis: a pilot study.
AB  - Arthritis affects both the physical and psychological abilities of people in all
      walks of life. There are currently no recommended effective 'disease-modifying'
      remedies. Therapists and physicians are therefore exploring possible benefits
      from non-conventional therapeutic approaches. The purpose is to assess the
      changes in fitness and psychosocial outcomes of six doctor-referred patients as a
      result of participating in the I Can Move Again (ICMA) program. Six female
      participants diagnosed with arthritis were recruited from a local family
      practitioner. The subjects participated in a series of daily classes for 12 weeks
      including massage, mindfulness, bounce-back chairs, resistance chairs, aerobic
      and anaerobic training, rebounders, and whole body vibration platform Tai Chi.
      Demographic, psychosocial, and physical data were collected at the ICMA and at Y
      Be-Fit (Provo, UT). Significant pre to post mean differences were found for sit
      ups (F (1,8) =5.42 P =0.048), chair stand (F (1,10) =6.622 P =0.028), arm curl (F
      (1,10) =14.379 P =0.004), six-minute walk test distance (F (1,9)= 19.188
      P=0.002), and speed (F,(1,8) =13.984 P =0.006), and rotation right (F (1,10)
      =8.921 P =0.014) and left (F (1,10) =11.373 P =0.007), in 27 of the 61-item
      questionnaire. The preliminary data on the six subjects lacked sufficient
      statistical power to detect the significant differences that could exist, thus
      committing a Type II error, but it is important to note an overall, substantial
      trend in improvement in the patients' physical outcomes and psychosocial
      perceptions associated with improvements in activities of daily living. 

PMID- 24860734
TI  - Antidiabetic activity of polyherbal formulation in streptozotocin - nicotinamide
      induced diabetic wistar rats.
AB  - Glycosmis pentaphylla, Tridax procumbens, and Mangifera indica are well-known
      plants available throughout India and they are commonly used for the treatment of
      various diseases including diabetes mellitus. The antidiabetic activity of the
      individual plant parts is well known, but the synergistic or combined effects are
      unclear. The concept of polyherbalism has been highlighted in Sharangdhar
      Samhita, an Ayurvedic literature dating back to 1300 AD. Polyherbal formulations
      enhance the therapeutic action and reduce the concentrations of single herbs,
      thereby reducing adverse events. The aim of the present study is to formulate a
      polyherbal formulation and evaluate its antidiabetic potential in animals. The
      polyherbal formulation was formulated using the ethanol extracts of the stem bark
      of G. pentaphylla, whole plant of T. procumbens, and leaves of M. indica. The
      polyherbal formulation contains the ethanol extracts of G. pentaphylla, T.
      procumbens, and M. indica in the ratio of 2:2:1. The quality of the finished
      product was evaluated as per the World Health Organization's guidelines for the
      quality control of herbal materials. The quality testing parameters of the
      polyherbal formulation were within the limits. Fingerprint analysis of the
      polyherbal formulation showed effective separation at 366 nm, and it revealed
      that the active compound present in the polyherbal formulation and the active
      compounds present in all the three extracts were the same. The acute toxicity
      studies of the polyherbal formulation did not show any toxic symptoms in doses up
      to 2000 mg/kg over 14 days. The oral antidiabetic activity of the polyherbal
      formulation (250 and 500 mg/kg) was screened against streptozotocin (50 mg/kg;
      i.p.) + nicotinamide (120 mg/kg; i.p.) induced diabetes mellitus in rats. The
      investigational drug was administered for 21 consecutive days, and the effect of
      the polyherbal formulation on blood glucose levels was studied at regular
      intervals. At the end of the study, the blood samples were collected from all the
      animals for biochemical estimation, and the animals were sacrificed and the liver
      and pancreatic tissues were collected for histopathologic analysis. Polyherbal
      formulation showed significant antidiabetic activity at 250 and 500 mg/kg,
      respectively, and this effect was comparable with that of glibenclamide. The
      antidiabetic activity of polyherbal formulation is supported by biochemical and
      histopathologic analysis. 

PMID- 24860735
TI  - Drimane-Type Sesquiterpene Coumarins from Ferula gummosa Fruits Enhance
      Doxorubicin Uptake in Doxorubicin-Resistant Human Breast Cancer Cell Line.
AB  - Multidrug resistance (MDR) is the main cause of failure in the chemotherapy of
      cancer patients. The present study aimed to evaluate the effects of sesquiterpene
      coumarins of Ferula gummosa fruits on P-glycoprotein (P-gp)-mediated MDR. Drimane
      type sesquiterpene coumarins from the fruits of F. gummosa were extracted with
      dichloromethane and subjected to column chromatography. The effects of the
      isolated compounds on P-gp-mediated MDR were evaluated in the breast cancer cell
      line MCF-7 which shows high resistance to doxoribicin (MCF-7/Dox). Phytochemical
      investigation of dichloromethane extract of F. gummosa fruits resulted in three
      sesquiterpene coumarins including conferone (1), mogoltacin (2), and feselol (3).
      The structures of these compounds were confirmed by 1D and 2D Nuclear Magnetic
      Resonance (NMR) spectroscopy. Exposure of cells to conferone, mogoltacin,
      feselol, and verapamil (positive control) enhanced doxorubicin uptake by MCF
      7/Dox cells. This effect was dose dependent, but varied with the structure of the
      chemical. At 25 MUM, all the tested sesquiterpene coumarins restored at least 50%
      of the reference uptake (uptake by sensitive cells); but at 10 MUM, their potency
      varied where conferone showed the highest potency and feselol showed the lowest
      potency. Conferone, mogoltacin, and feselol from F. gummosa suppress P-gp
      mediated drug efflux in highly resistant human breast cancer cells. 

PMID- 24860736
TI  - Effect of Oxidative Phytochemicals on Nicotine-stressed UMNSAH/DF-1 Cell Line.
AB  - Nicotine is a parasympathomimetic alkaloid found in the nightshade family of
      plants (Solanaceae) and is a cholinergic drug. It acts directly by stimulating
      the nicotinic or muscarinic receptors or indirectly by inhibiting cholinesterase,
      promoting acetylcholine release, or by other mechanisms. 3% of tobacco or one
      cigarette yields 1 mg of nicotine. As nicotine enters the body, it disturbs the
      healthy functioning of the body. In this study, we isolated UMNSAH/DF-1 cell line
      from Gallus gallus. For this, 9 +/- 2 day old chicken embryo was taken. This was
      followed by the extraction of nicotine (1 mg/ml) from cigarette. The cells were
      then given nicotine stress and were observed for blackening after 24 h of
      incubation under 40* resolution of microscope. It was found that this blackening
      of the cells was permanent even after a wash with 1* phosphate-buffered saline
      (PBS) followed by replenishing the medium. The phytochemicals extracted were from
      the dried powder, which included Curcuma longa ( Jiang Huang; Turmeric) 40 mg/ml,
      Azadirachta indica (neem) 50 mg/ml, Cinnamomum tamala (bay leaf) 30 mg/ml,
      Camellia sinensis ( Lu Cha; Green Tea) 100 mg/ml, and Ocimum sanctum (tulsi) 30
      mg/ml. When applied to nicotine-stressed cells, it was observed that ursolic acid
      in neem recovered 70%, followed by 65% recovery by tulsi (having triterpenoid),
      50% recovery by the catechins in Ca. sinensis, and very little recovery shown by
      Ci. tamala. Due to the yellow coloration of the cells by Cu. longa, much could
      not be inferred, although it was inferable that it had resulted in little
      effects. Mixtures of these phytochemicals were used, and it was found that neem:
      tulsi diluted in 3:1 ratio was highly effective and cell recovery was almost 80%.
      68% was recovered by tulsi: green tea in a ratio 1:3 and 42% by turmeric:green
      tea in a ratio of 1:5. 

PMID- 24860737
TI  - Polysaccharide Isolated from Zizyphus jujuba ( Hong Zao) Inhibits Interleukin-2
      Production in Jurkat T Cells.
AB  - Zizyphus jujuba ( Hong Zao), a traditional Chinese herb widely used in many Asian
      countries, has been shown to possess vital biological activities such as anti
      cancer activity. The objective of this study was to evaluate the immunomodulatory
      effect of deproteinated polysaccharide (DP) isolated from Z. jujuba. The DP
      isolated from Z. jujuba consisted of two polysaccharide fractions and their
      molecular weights (MWs) were found to be 143,108 and 67,633 Da, respectively. The
      DP could significantly decrease interleukin (IL)-2 production in
      phytohemagglutinin (PHA)-activated Jurkat T cells in a dose-dependent manner
      after 48 h of incubation, with the inhibition being 47.5%, 61.2%, and 81.7% for
      DP concentrations of 0.75, 1.75, and 2.5 mg/ml, respectively. Thus, our study
      showed that DP isolated from Z. jujuba may possess anti-inflammatory activity as
      it could significantly reduce IL-2 production in activated Jurkat T cells. 

PMID- 24860739
TI  - The benefit of a case report.

PMID- 24860740
TI  - Cerebriform intradermal nevus: A rare entity and its associations.

PMID- 24860738
TI  - Exosomal Proteome Profiling: A Potential Multi-Marker Cellular Phenotyping Tool
      to Characterize Hypoxia-Induced Radiation Resistance in Breast Cancer.
AB  - Radiation and drug resistance are significant challenges in the treatment of
      locally advanced, recurrent and metastatic breast cancer that contribute to
      mortality. Clinically, radiotherapy requires oxygen to generate cytotoxic free
      radicals that cause DNA damage and allow that damage to become fixed in the
      genome rather than repaired. However, approximately 40% of all breast cancers
      have hypoxic tumor microenvironments that render cancer cells significantly more
      resistant to irradiation. Hypoxic stimuli trigger changes in the cell
      death/survival pathway that lead to increased cellular radiation resistance. As a
      result, the development of noninvasive strategies to assess tumor hypoxia in
      breast cancer has recently received considerable attention. Exosomes are secreted
      nanovesicles that have roles in paracrine signaling during breast tumor
      progression, including tumor-stromal interactions, activation of proliferative
      pathways and immunosuppression. The recent development of protocols to isolate
      and purify exosomes, as well as advances in mass spectrometry-based proteomics
      have facilitated the comprehensive analysis of exosome content and function.
      Using these tools, studies have demonstrated that the proteome profiles of tumor
      derived exosomes are indicative of the oxygenation status of patient tumors. They
      have also demonstrated that exosome signaling pathways are potentially targetable
      drivers of hypoxia-dependent intercellular signaling during tumorigenesis. This
      article provides an overview of how proteomic tools can be effectively used to
      characterize exosomes and elucidate fundamental signaling pathways and survival
      mechanisms underlying hypoxia-mediated radiation resistance in breast cancer.

PMID- 24860741
TI  - Role of the ACTH test and estimation of a safe dose for high potency steroids in
      vitiligo: A prospective randomized study.
AB  - BACKGROUND: Topical corticosteroids are used as first line of therapy for
      vitiligo, although side effects such as adrenal insufficiency are possible.
      OBJECTIVES: To establish the role of ACTH test before, during, and after
      treatment with high potency topical steroids; to determine if adrenal
      insufficiency occurs secondary to the use of high potency topical steroids in
      patients with vitiligo and intact cutaneous barrier; and also to determine
      response to treatment and side effects. MATERIALS AND METHODS: Forty-four adults
      with non-segmental vitiligo affecting 20% or less of the body surface area were
      included and randomized to receive topical clobetasol propionate 0.05% cream
      (group 1) or placebo (group 2) for 12 weeks, with a maximum dose of 50 g per
      week. The placebo group was crossed over after week 6 and started on clobetasol
      until completion of the study. Serum cortisol levels with the 1 MUg ACTH test
      were determined at baseline and on weeks 6 and 12. RESULTS: No adrenal
      insufficiency was detected nor statistical significance was achieved when
      comparing cortisol levels between and within the groups at baseline and weeks 6
      and 12. Group 1 had a better response to therapy but with more side effects.
      CONCLUSIONS: Doses of 50 g or less per week of clobetasol during a period of 12
      weeks are safe on adult vitiligo patients, although local side effects are
      possible. Repigmentation rates were incomplete with single steroid therapy,
      making combined therapy a better option.

PMID- 24860743
TI  - Efficacy and safety of terbinafine hydrochloride 1% cream vs eberconazole nitrate
      1% cream in localised tinea corporis and tinea cruris.
AB  - AIMS: To study and compare the efficacy and safety of topical terbinafine
      hydrochloride 1% cream and eberconazole nitrate 1% cream in localized tinea
      corporis and cruris. METHODS AND MATERIALS: Patients were randomized after
      considering various inclusion and exclusion criteria into two groups. Group A
      (treated with terbinafine 1% cream for 3 weeks) and group B (treated with
      eberconazole 1% cream for 3 weeks). The sample size was of 30 patients with 15
      patients in each group. Assessment of clinical improvement, KOH mount and culture
      was done weekly up to 3 weeks to assess complete cure. RESULTS: On comparison
      between the two groups, it was observed that eberconazole nitrate 1% cream was as
      effective as terbinafine hydrochloride 1% cream at the end of first (Non
      sisgnificant (NS); P = 0.608, 1.00), second (NS; P = 0.291,0.55), and third (P =
      1.00, 1.00) weeks with statistically nonsignificant clinical and mycological
      values. In both the groups, clinically no significant local side effects were
      noticed. CONCLUSIONS: The newer fungistatic eberconazole nitrate 1% cream was as
      effective as the fungicidal terbinafine hydrochloride 1% cream. Both the drugs
      showed good tolerability with no adverse effects.

PMID- 24860742
TI  - Total serum immunoglobulin E in patients with alopecia areata.
AB  - CONTEXT: Alopecia areata (AA) is a common form of localized, non-scarring hair
      loss. The pathogenesis of the disease is unknown. Previous evidence suggested the
      involvement of Th2 cytokines in disease pathogenesis. AIM: To determine serum
      level of total IgE, this is mainly influenced by Th2 cytokines, in Egyptian
      patients with AA. MATERIALS AND METHODS: Fifty subjects with AA (28 males and 22
      females) were selected from Dermatology Outpatient Clinic, Menoufiya University
      Hospital from February 2012 to December 2012. Subjects with other conditions that
      might elevate serum IgE were excluded from the study. Fifty age- and sex-matched
      healthy subjects were selected as a control group. Venous blood samples were
      taken from cases and controls for measurement of total serum IgE by enzyme-linked
      immunosorbent assay. Skin biopsy was taken from every case from an active area of
      hair loss. RESULTS: Total serum IgE was elevated in 27 (54%) cases. Its values
      among patients ranged from 13.5 IU/ml to 780 IU/ml. There was a statistically
      significant difference between cases and controls with regard to mean value of
      serum IgE (P < 0.05). Mean value of IgE did not vary significantly with disease
      severity, patients' age, patients' gender, disease duration, site of lesions, and
      positive family history of AA. No correlation was found between serum IgE levels
      and histopathological changes detected in examined cases. CONCLUSIONS: Total
      serum IgE is elevated in AA. This elevation is not related to age, gender,
      disease duration, disease severity, site of affection or family history of AA.

PMID- 24860744
TI  - Metabolic syndrome in patients with psoriasis: A comparative study.
AB  - BACKGROUND: Psoriasis patients are at increased risk of developing the metabolic
      syndrome (MS). Proinflammatory cytokines such as tumor necrosis factor-alpha,
      interleukin-6 that are increased in the psoriatic plaques are known to contribute
      to features of MS such as hypertension, dyslipidemia and insulin resistance.
      AIMS: (1) To establish the frequency of MS in patients with psoriasis. (2) To
      study the risk factors associated with MS in psoriasis. MATERIALS AND METHODS: A
      hospital based comparative study was conducted involving 40 adult patients with
      psoriasis and 40 age- and sex-matched controls. All participants were evaluated
      for components of MS. RESULTS: Both groups included 31 males and 9 females. The
      mean age of the cases and controls were 49.95 years and 49.35 years,
      respectively. Psoriasis patients with MS had a statistically significant higher
      mean age (56.31 +/- 11.36 years) compared with those without MS (46.89 +/- 11.51
      years). MS was present in 13 out of 40 (32.5%) patients with psoriasis and 12 out
      of 40 (30%) controls; this difference was not statistically significant. Higher
      age and female gender correlated with the presence of MS in psoriasis patients.
      The presence of MS in psoriasis patients was statistically independent of
      psoriasis area severity index score, body surface area involvement or psoriatic
      arthropathy. CONCLUSION: Our results suggest that there is no close correlation
      between psoriasis and MS in South Indian patients.

PMID- 24860745
TI  - Clinical profile of cutaneous manifestations with and without hematologic
      disease: A comparative study.
AB  - AIM: The aim was to study the clinical profile of cutaneous manifestations of
      hematologic disorders and to compare it with that of non-hematologic disorders.
      MATERIALS AND METHODS: Cutaneous manifestations of hematologic diseases fall in
      seven well-defined categories. A total of 153 outpatients with skin
      manifestations fitting in these categories were enrolled in a comparative study
      of 1-year duration. Clinical profile of these cutaneous manifestations was
      studied and any underlying hematologic disorder was ruled out with the help of a
      hematologist. Difference in the clinical profile of cutaneous manifestations with
      and without hematologic diseases was studied. RESULT: Of the 26,174 outpatients
      during the study period, 153 had cutaneous manifestations fitting in the
      categories of hematologic disorders. Of these 153 patients, 33 had hematologic
      disease as the cause of their cutaneous manifestation (21.57%), whereas 78.42%
      had no hematologic disorder. Disorders of hemostasis formed the largest group
      (36%) followed by cutaneous deposits/infiltrations (15%), vesiculobullous
      disorders (6%), and cutaneous vasculitis (9%) were least commonly associated with
      hematologic disorders. CONCLUSION: Hematologic diseases are associated with
      complex array of cutaneous manifestations. The incidence of hematologic disease
      associated cutaneous manifestations was 0.13%. Findings of this study will help
      dermatologists and physicians with the early recognition of cutaneous signs of
      hematologic disorders.

PMID- 24860746
TI  - A burst in the incidence of viral exanthems.
AB  - BACKGROUND: Vaccines have a major role in eradication programs of viral diseases.
      Vaccines against measles, rubella, and varicella are included in the vaccination
      schedules for children in most countries. OBJECTIVE: A comparative analysis
      between 2011 and 2012 was performed to investigate if the number of patients with
      viral exanthemas reported to our clinic in 2012 was increased. MATERIALS AND
      METHODS: PATIENTS WERE GROUPED IN FOUR CATEGORIES: rubella, measles, varicella
      and other viral exanthemas. RESULTS: Between January and April 2011, there were
      registered 37 cases with viral exanthemas: 69.5% presented with varicella and
      30.5% with other viral exanthemas. Between January and April 2012, there were 178
      cases registered with viral eruption, of which 37% were of other viral
      exanthemas, 35.4% rubella, 19.7% measles and 7.9% varicella. The highest
      incidence was seen in patients aged between 20 and 29 years (52.2%), with 21%
      having measles, 32.2% rubella, 9% varicella and 37.6% having other exanthemas. In
      2012, the number of cases of viral exanthemas increased 5 times, with important
      outbreaks of new cases of measles and rubella. CONCLUSIONS: Although vaccines
      against measles and rubella were being used since 1979 and 1998 respectively, it
      was only in 2004, that these vaccines became part of the mandatory vaccination
      schedule. Although persons under 32 years should be protected against measles
      infection if they are previously vaccinated, more than 90% of the registered
      cases of measles occurred in such patients. The patients registered between
      January and April 2011 were mostly pediatric. Adults also were much more affected
      with measles, rubella, or varicella viruses in 2012 than in 2011.

PMID- 24860747
TI  - Pseudoepitheliomatous keratotic and micaceous balanitis of Civatte.
AB  - Pseudoepitheliomatous, keratotic, and micaceous balanitis is a rare condition
      characterized by verrucous excrescences with scaling. Most patients are over the
      age of 50 and frequently have been circumcised for phimosis in adult life. We
      present here a case of 35-year-old male patient with long standing phimosis
      presenting with a firm whitish plaque on the glans penis. The crusts were
      micaceous in nature. Histopathologically, there was pseudoepitheliomatous
      hyperplasia with acanthosis and no cellular atypia. The condition was explained
      to the patient and treatment options discussed. The patient was started on
      topical 5-fluorouracil cream on a daily basis as he did not express consent for
      operative intervention. 

PMID- 24860748
TI  - Aggressive angiomyxoma.
AB  - Myxoid tumors are a heterogeneous group of lesions characterized by a marked
      abundance of extra cellular mucoid (myxoid) matrix.[1] The term aggressive
      emphasizes the often infiltrative nature of the tumor and its frequent
      association with recurrence.[2] A case of aggressive angiomyxoma arising from the
      vagina in a 55-year-old woman is reported for its rarity. 

PMID- 24860749
TI  - A rare presentation of Klippel-Trenaunay syndrome.
AB  - The Klippel-Trenaunay syndrome (KTS) is a congenital disorder characterized by
      capillary malformation, varicosities and bony and soft tissue hypertrophy. This
      disease has several morbidities like bleeding, deep venous thrombosis, embolic
      complications and in some cases enlargement of limb that may require amputation.
      Vascular malformations are segmented and never cross midline. However, we came
      across a case, a 45-year-old male, who presented with varicosity of veins and
      deformity of left lower limb besides cavernous hemangiomas (port-wine stains)
      scattered all over his face, chest, back, gluteal region, groin and legs since
      birth. Multiple paravertebral soft tissue masses and bladder hypertrophy were
      also noted due to involving neurofibromatosis. Simultaneous occurrence of KTS and
      neurofibromatosis is rarely seen in clinical practice. 

PMID- 24860750
TI  - Segmental lichen planus pigmentosus: An unusual presentation.
AB  - Lichen planus pigmentosus (LPP) is a distinct clinical entity commonly
      encountered in the Indian population. It is considered a variant of lichen planus
      (LP). A 40-year-old male presented with asymptomatic hyperpigmented macules in a
      segmental distribution since 10 years that were clinically and
      histopathologically suggestive of LPP. We propose the terminology "segmental
      lichen planus pigmentosus" and report this unusual presentation. 

PMID- 24860751
TI  - Could cryosurgery be an alternative treatment for basal cell carcinoma of the
      vulva?
AB  - Basal cell carcinomas (BCC) on the genital area account for less than 1% of all
      BCCs. Surgical management is indicated. Recurrence rate of vulvar BCC has been
      reported to be 10-20%. Mohs micrographic surgery (MMS) is a superior surgical
      option. Other treatments include radiation and topical immuntherapy. Cryosurgery
      for vulvar BCC has not been reported. We present the case of a 88-year-old
      Hispanic woman with a vulvar ulcer that was confirmed as BCC by histopathology
      and treated with liquid nitrogen cryosurgery. Control biopsy was performed on day
      90 was negative for BCC. No clinical evidence of recurrence was detected after
      one year. Although, the vulva is considered to be a high-risk site with respect
      to BCC and MMS is the gold standard for treatment, the delicate nature of the
      area may preclude complete removal by a surgical technique without compromising
      vital anatomical function. Liquid nitrogen cryosurgery uses the effects of
      extreme cold to effect deep destruction of the tumor and surrounding tissues.
      This is the first report of a vulvar BCC successfully treated with liquid
      nitrogen cryosurgery. We suggest this technique could be of benefit as an
      alternative treatment in cases where excisional procedures cannot be performed. 

PMID- 24860752
TI  - Hyperpigmentation in photo exposed patches of vitiligo following tacrolimus
      therapy.
AB  - Vitiligo is an acquired pigmentary disorder, clinically characterized by
      depigmented macules caused by destruction of melanocytes in the affected skin.
      Half of all patients develop the disease in childhood and adolescence before the
      age of 20 years, making vitiligo an important skin disease of childhood. There
      are numerous studies in the literature that suggest the efficacy of topical
      tacrolimus in vitiligo, without serious adverse effects. We describe a case of
      vitiligo in a pediatric patient who developed hyperpigmentation in the
      periorbital lesions of vitiligo with the use of topical tacrolimus. To the best
      of our knowledge, this is only the second such reported occurrence in a patient
      with vitiligo. 

PMID- 24860753
TI  - Non pigmenting mucosal fixed drug eruption due to tadalafil: A report of two
      cases.
AB  - Various 'sex-stimulant' medicines with fancy names and attractive packaging are
      available over the counter. Most contain phosphodiesterase 5 inhibitors in
      various strengths, often with herbal additions. These drugs are used erratically
      by the lay public, driven by folklore that such usage leads to increase in the
      length, girth or firmness of the penis. Such indiscriminate use by an otherwise
      healthy population leads to undue side effects. 

PMID- 24860754
TI  - Pansclerotic morphea: A male child with hemiatrophy of lower limb.
AB  - Morphea is a variant of localized scleroderma in which lesions are usually
      limited to the skin and subcutaneous tissue. Pansclerotic morphea is a rare
      atrophying and sclerosing type of morphea. It can follow a comparatively benign
      course with spontaneous resolution of symptoms, or sometimes can lead to a
      variety of complications resulting in progressive disability. We report a case of
      Pansclerotic morphea in an 8-year-old male child involving one lower extremity
      with extension to the lower trunk. It was associated with deformity and
      hemiatrophy of that limb, leading to restriction of normal day-to-day activity.
      The case is being reported in view of its rare occurrence in conjunction with
      other rarer features. 

PMID- 24860755
TI  - Rud's syndrome.
AB  - Rud's syndrome is a rare autosomal recessive hereditary disorder characterized by
      congenital ichthyosis, epilepsy, dwarfism, sexual infantilism, polyneuritis, and
      macrocytic anemia. We report here an interesting case of this disorder in an 18
      year-old girl for its rarity and academic interest. 

PMID- 24860756
TI  - Pseudoxanthoma elasticum and nephrocalcinosis: Incidental finding or an
      infrequent manifestation?
AB  - Pseudoxanthoma elasticum (PXE) is an inherited disorder characterized by
      generalized fragmentation and progressive calcification of elastic tissue. We
      report two sporadic cases of PXE, both of whom presented with asymptomatic
      yellowish papules over the flexural sites for cosmetic reasons. Histopathological
      findings on hematoxylin and eosin and Verhoeff-Van Gieson (VVG) staining were
      classical of PXE. In addition to this, renal calcification was documented on
      plain radiography of kidneys, ureters, and bladder (KUB) in both the cases.
      Paucity of literature describing the association of nephrocalcinosis with PXE
      prompted the present report. 

PMID- 24860757
TI  - Nevirapine induced toxic epidermal necrolysis and non-Hodgkin lymphoma in a Human
      Immunodeficiency Virus positive patient.
AB  - Nevirapine, a non-nucleoside reverse transcriptase inhibitor (NNRTI) is one of
      the important components of highly active antiretroviral therapy. It is sometimes
      associated with life-threatening adverse reactions. Here we report one such
      patient who developed toxic epidermal necrolysis (TEN), leucopenia and
      hepatotoxicity secondary to intake of nevirapine. This patient was also diagnosed
      to have non-Hodgkin lymphoma grade IV of anal canal for which he was given
      radiotherapy and two cycles of chemotherapy. The treating physicians should
      carefully monitor patients on NNRTI-based antiretroviral therapy so that
      fatalities due to adverse drug reactions can be prevented with timely
      intervention. 

PMID- 24860758
TI  - Livedo reticularis in type 2 lepra reaction: A rare presentation.
AB  - Type 2 lepra reaction or erythema nodosum leprosum (ENL) is an immune complex
      syndrome that occurs mostly in lepromatous leprosy and sometimes in borderline
      lepromatous leprosy patients. We present an untreated case of lepromatous
      leprosy, who presented with type 2 lepra reaction and livedo reticularis. Livedo
      reticularis, though seen in lucio phenomenon, is not a part of type 2 lepra
      reaction. The case is being reported for its rarity. 

PMID- 24860759
TI  - Sjogren-Larsson syndrome: A study of clinical symptoms in six children.
AB  - Sjogren-Larsson syndrome (SLS) is a rare autosomal recessive disorder
      characterized by triad of congenital ichthyosis, spastic paresis, and mental
      retardation. It is an inborn error of lipid metabolism caused by deficiency of
      the enzyme fatty aldehyde dehydrogenase. We report our observations of six
      children with SLS. 

PMID- 24860760
TI  - Juvenile pemphigoid nodularis: Report of a rare case.
AB  - Bullous pemphigoid is an autoimmune blistering disease that is rare in childhood.
      Pemphigoid nodularis is a variant of BP that is exceedingly rare in children.
      Pemphigoid nodularis is characterized by overlapping clinical features of both
      prurigo nodularis and BP. We report here a case of pemphigoid nodularis in an 11
      year-old boy. 

PMID- 24860761
TI  - Proteus syndrome: A rare cause of gigantic limb.
AB  - A congenital disorder with variable manifestations, including partial gigantism
      of the hands and feet with hypertrophy of soles, nevi, hemihypertrophy,
      gynecomastia, macrocephaly and other skull abnormalities, and abdominal
      lipomatosis. The cause is unknown, although a genetic origin, generally of
      autosomal-dominant transmission, has been conjectured. Symptoms can be treated,
      but there is no known cure. We present the case of a young male with grotesque
      overgrowth of the right lower limb, splenomegaly and multiple nevi. Angiography
      revealed venous malformation within the limb. The findings are in conformity to
      the criteria for the Proteus syndrome. 

PMID- 24860762
TI  - Hypomelanosis of Ito with an unusual pulmonary abnormality in an infant.
AB  - Hypomelanosis of Ito (HI) is a neurocutaneous syndrome characterized by
      hypopigmented cutaneous lesions and extracutaneous manifestations frequently
      affecting the nervous system and the musculoskeletal system. Dysmorphic features,
      dental, ophthalmic, gastrointestinal, cardiac, and renal abnormalities are
      described in a minority of patients. The authors describe a 4-month-old infant
      having HI with unusual pulmonary hypoplasia that has not been reported so far. 

PMID- 24860763
TI  - Medallion-like dermal dendrocytoma.
AB  - Medallion-like dermal dendrocytoma is a benign cutaneous neoplasm that mimics
      dermatofibrosarcoma protuberans histologically. The distinction between these two
      entities is critical to prevent unnecessary wide excisions. Herein we describe an
      acquired MLDD in a 55-year-old female. 

PMID- 24860765
TI  - Antioxidants in dermatology.
AB  - Antioxidants neutralize free radicals produced by various environmental insults
      such as ultraviolet radiation, cigarette smoke and air pollutants, thereby
      preventing cellular damage. The role of oxidative stress and antioxidants is
      known in diseases like obesity, atherosclerosis, and Alzheimer's disease. Herein
      we discuss the effects of oxidative stress on the skin and role of antioxidants
      in dermatology. 

PMID- 24860764
TI  - Human pigmentation: A side effect adapted from a primitive organism's survival,
      acting through cell attachment with an affinity for the keratinocyte and for
      elastin: Part I.
AB  - Pigmentation featured millions of years ago and perhaps began with an amoeba
      frightening off a predator with some agent such as dopamine to prevent its
      attachment for phagocytosis by an enemy. This paper suggests that the
      environmental forces of grip and stick deserve greater emphasis and that
      mechanical forces involved in grip and stick or release from attachment, all
      point to control of proteases underlying pigmentation. There is an affinity for
      elastin as a pathway for melanin to exit its peripheral location in the epidermis
      into lymphatics and play a humeral role in defense mechanisms. The hair follicle
      follows the epidermal-dermal pattern of behavior with an affinity for elastin, a
      controlling function of melanin and through the bulge, an influence of mechanical
      forces and control by protease inhibitors. 

PMID- 24860766
TI  - Pagetoid dyskeratosis of the forehead.

PMID- 24860767
TI  - Pemphigus vulgaris: A dermatological sequel of severe H1N1 infection.

PMID- 24860768
TI  - Verrucous carcinoma of the finger: A rare site of occurrence.

PMID- 24860769
TI  - Remote reverse Koebner phenomenon in generalized granuloma annulare.

PMID- 24860770
TI  - Acrocyanosis with intrahepatic carcinoid tumor.

PMID- 24860771
TI  - A study of the prevalence and precipitating factors of pruritus in pityriasis
      versicolor.

PMID- 24860772
TI  - Idiopathic cutaneous pseudolymphoma: An enigma.

PMID- 24860774
TI  - SkIndia Quiz 13: Scars on the skin, scars in the heart.

PMID- 24860775
TI  - Chronic, fluctuating, grouped, erythematous papules around the mouth.

PMID- 24860776
TI  - Suction purpura.

PMID- 24860777
TI  - Palmoplantar keratoderma with dental abnormalities.

PMID- 24860778
TI  - A classical case of punctate palmoplantarkeratoderma: A rare entity.

PMID- 24860779
TI  - Elastosis perforans serpiginosa.

PMID- 24860780
TI  - Navigating the rapids: the development of regulated next-generation sequencing
      based clinical trial assays and companion diagnostics.
AB  - Over the past decade, next-generation sequencing (NGS) technology has experienced
      meteoric growth in the aspects of platform, technology, and supporting
      bioinformatics development allowing its widespread and rapid uptake in research
      settings. More recently, NGS-based genomic data have been exploited to better
      understand disease development and patient characteristics that influence
      response to a given therapeutic intervention. Cancer, as a disease characterized
      by and driven by the tumor genetic landscape, is particularly amenable to NGS
      based diagnostic (Dx) approaches. NGS-based technologies are particularly well
      suited to studying cancer disease development, progression and emergence of
      resistance, all key factors in the development of next-generation cancer Dxs.
      Yet, to achieve the promise of NGS-based patient treatment, drug developers will
      need to overcome a number of operational, technical, regulatory, and strategic
      challenges. Here, we provide a succinct overview of the state of the clinical NGS
      field in terms of the available clinically targeted platforms and sequencing
      technologies. We discuss the various operational and practical aspects of
      clinical NGS testing that will facilitate or limit the uptake of such assays in
      routine clinical care. We examine the current strategies for analytical
      validation and Food and Drug Administration (FDA)-approval of NGS-based assays
      and ongoing efforts to standardize clinical NGS and build quality control
      standards for the same. The rapidly evolving companion diagnostic (CDx) landscape
      for NGS-based assays will be reviewed, highlighting the key areas of concern and
      suggesting strategies to mitigate risk. The review will conclude with a series of
      strategic questions that face drug developers and a discussion of the likely
      future course of NGS-based CDx development efforts. 

PMID- 24860781
TI  - Modeling platinum sensitive and resistant high-grade serous ovarian cancer:
      development and applications of experimental systems.
AB  - High-grade serous ovarian cancer remains the most common sub-type of ovarian
      cancer and, characterized by high degrees of genomic instability and
      heterogeneity, is typified by a transition from early response to acquired
      resistance to platinum-based chemotherapy. Conventional models for the study of
      ovarian cancer have been largely limited to a set of relatively poorly
      characterized immortalized cell lines and recent studies have called into
      question the validity of some of these as reliable models. Here, we review new
      approaches and models systems that take into account advances in our
      understanding of ovarian cancer biology and advances in the technology available
      for their generation and study. We discuss primary cell models, 2D, 3D, and
      organotypic models, and "paired" sample approaches that capture the evolution of
      chemotherapy failure within single cases. We also overview new methods for non
      invasive collection of representative tumor material from blood samples. Adoption
      of such methods and models will improve the quality and clinical relevance of
      ovarian cancer research. 

PMID- 24860782
TI  - Mysteries of TGF-beta Paradox in Benign and Malignant Cells.
AB  - TGF-beta regulates a wide range of biological functions including embryonic
      development, wound healing, organogenesis, immune modulation, and cancer
      progression. Interestingly, TGF-beta is known to inhibit cell growth in benign
      cells but promote progression in cancer cells; this phenomenon is known as TGF
      beta paradox. To date, the mechanism of this paradox still remains a scientific
      mystery. In this review, we present our experience, along with the literature, in
      an attempt to answer this mystery. First, we observed that, on TGF-beta
      engagement, there is a differential activation of Erk between benign and cancer
      cells. Since activated Erk is a major mediator in tumor progression and
      metastasis, a differentially activated Erk represents the answer to this mystery.
      Second, we identified a key player, PP2A-B56alpha, which is differentially
      recruited by the activated type I TGF-beta receptor (TBRI) in benign and tumor
      cells, resulting in differential Erk activation. Finally, TGF-beta stimulation
      leads to suppressed TBRs in tumor cells but not in benign cells. This
      differentially suppressed TBRs triggers differential recruitment of PP2A-B56alpha
      and, thus, differential activation of Erk. The above three events explain the
      mysteries of TGF-beta paradox. Understanding the mechanism of TGF-beta paradox
      will help us to predict indolent from aggressive cancers and develop novel anti
      cancer strategies. 

PMID- 24860783
TI  - Radio(chemo)therapy in Elderly Patients with Esophageal Cancer: A Feasible
      Treatment with an Outcome Consistent with Younger Patients.
AB  - BACKGROUND: Although the prevalence of esophageal cancer increases in elderly
      patients, its clinical history and outcome after treatment remain poorly
      described. METHODS: Between January 2001 and December 2011, 58 patients (pts)
      older than 75 years received 3D-conformal radiotherapy (mean dose 51 Gy) in two
      French cancer centers. 47/58 (82%) patients received concomitant chemotherapy
      (with CDDP and/or FU regimens) and 8 patients underwent surgery after primary
      radiochemotherapy (RCT). RESULTS: Median age was 77.9 years and the performance
      status (PS) was 0 or 1 in 89%. Tumors were mainly adenocarcinoma of lower
      esophagus or gastroesophageal junction (n = 51, 89%), T3T4 (n = 54, 95%), and N1
      (n = 44, 77%). The mean follow-up was 21.9 months. In the overall population, the
      median progression-free survival was 9.6 months and median overall survival (OS)
      was 14.5 months. Using univariate analysis, OS was significantly associated with
      age (p = 0.048), PS (p < 0.001), and surgery (p = 0.035). 35 (60.3%) and 18
      patients (31%) experienced grade 1-2 or 3-4 toxicity, respectively (CTCAE v4.0).
      CONCLUSION: Radiochemotherapy in elderly patients is a feasible treatment and its
      outcome is close to younger patient's outcome published in the literature.
      Surgical resection, after comprehensive geriatric assessment, should be
      recommended as the standard treatment for adenocarcinoma of lower esophagus or
      gastroesophageal junction in elderly patients with good PS and low co-morbidity
      profile, as it is in younger patients.

PMID- 24860784
TI  - Targeted nanoparticles for pediatric leukemia therapy.
AB  - The two major forms of leukemia, acute lymphoblastic leukemia (ALL) and acute
      myeloid leukemia (AML), account for about one-third of the malignancies diagnosed
      in children. Despite the marked successes in ALL and AML treatment, concerns
      remain regarding the occurrence of resistant disease in subsets of patients, the
      residual effects of therapy that often persist for decades beyond the cessation
      of treatment. Therefore, new approaches are needed to reduce or to avoid off
      target toxicities, associated with chemotherapy and their long-term residual
      effects. Recently, nanotechnology has been employed to enhance cancer therapy,
      via improving the bioavailability and therapeutic efficacy of anti-cancer agents.
      While in the last several years, numerous review articles appeared detailing the
      size, composition, assembly, and performance evaluation of different types of
      drug carrying nanoparticles, the description and evaluation of lipoprotein-based
      drug carriers have been conspicuously absent from most of these major reviews.
      The current review focuses on such information regarding nanoparticles with an
      emphasis on high density lipoprotein-based drug delivery systems to examine their
      potential role(s) in the enhanced treatment of children with leukemia. 

PMID- 24860785
TI  - The role of the tumor stroma in ovarian cancer.
AB  - The tumor microenvironment, consisting of stromal myofibroblasts, endothelial
      cells, and leukocytes, is growingly perceived to be a major contributor to the
      pathogenesis and disease progression in practically all cancer types. Stromal
      myofibroblasts produce angiogenic factors, proteases, growth factors, immune
      response-modulating proteins, anti-apoptotic proteins, and signaling molecules,
      and express surface receptors and respond to stimuli initiated in the tumor cells
      to establish a bi-directional communication network in the microenvironment to
      promote tumor cell invasion and metastasis. Many of these molecules are
      candidates for targeted therapy and the cancer stroma has been recently regarded
      as target for biological intervention. This review provides an overview of the
      biology and clinical role of the stroma in ovarian cancer. 

PMID- 24860786
TI  - Estrogen signaling and the DNA damage response in hormone dependent breast
      cancers.
AB  - Estrogen is necessary for the normal growth and development of breast tissue, but
      high levels of estrogen are a major risk factor for breast cancer. One mechanism
      by which estrogen could contribute to breast cancer is via the induction of DNA
      damage. This perspective discusses the mechanisms by which estrogen alters the
      DNA damage response (DDR) and DNA repair through the regulation of key effector
      proteins including ATM, ATR, CHK1, BRCA1, and p53 and the feedback on estrogen
      receptor signaling from these proteins. We put forward the hypothesis that
      estrogen receptor signaling converges to suppress effective DNA repair and
      apoptosis in favor of proliferation. This is important in hormone-dependent
      breast cancer as it will affect processing of estrogen-induced DNA damage, as
      well as other genotoxic insults. DDR and DNA repair proteins are frequently
      mutated or altered in estrogen responsive breast cancer, which will further
      change the processing of DNA damage. Finally, the action of estrogen signaling on
      DNA damage is also relevant to the therapeutic setting as the suppression of a
      DDR by estrogen has the potential to alter the response of cancers to anti
      hormone treatment or chemotherapy that induces DNA damage. 

PMID- 24860788
TI  - Integrin VLA-5 and FAK are Good Targets to Improve Treatment Response in the
      Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia.
AB  - Acute lymphoblastic leukemia bearing the Philadelphia chromosome is among the
      most difficult types of ALL to cure. However, the advent of targeted tyrosine
      kinase inhibitor (TKI) imatinib has ushered in a new era of treatments that have
      the potential to be less toxic to patients. Integrins and tyrosine kinases play
      important roles in mediating and transducing signals for cell survival and
      suppressing apoptosis. Focal adhesion kinase (FAK) is a non-receptor type
      tyrosine kinase that is constitutively activated in Ph+ ALL. We sought to
      investigate the specificity of integrin alpha5beta1 (VLA-5) on Ph+ leukemia by
      its expression and function. We found VLA-5 expression increases after serum
      starvation. Integrin alpha5 inhibitory antibody inhibited adhesion of Ph+
      leukemia to human fibronectin and acted synergistically with imatinib to induce
      Ph+ leukemia cell apoptosis. We used different strategies to block integrin
      signaling and knocked down the expression of integrin VLA-5 to observe the effect
      on proliferation and engraftment of Ph+ leukemia cells in immunodeficient mice.
      We found that blocking integrin activity by incubating Ph+ leukemia cells with
      disintegrin, a peptide inhibitor of integrins, or alpha5 inhibitory antibody, or
      knocking down the alpha5 integrin subunit impaired and delayed the engraftment of
      Ph+ leukemia in immunodeficient mice. We then treated mice xenografted with Ph+
      leukemia cells with the FAK inhibitor TAE226 in combination with a BCR-ABL TKI
      nilotinib. While 2 weeks of treatment with TAE226 alone did not significantly
      inhibit leukemia growth in mice, TAE226 in combination with nilotinib provided
      the most optimum growth inhibition at 4-6 weeks. We conclude that blocking VLA-5
      signaling or combining FAK inhibitors with TKI targeting BCL/ABL might be good
      strategies to improve treatments in patients with Ph+ ALL. By altering Ph+
      leukemia cell interactions with the microenvironment, we may increase their
      susceptibility to therapy targeting BCR/ABL. 

PMID- 24860787
TI  - Genetic Modeling of PIM Proteins in Cancer: Proviral Tagging and Cooperation with
      Oncogenes, Tumor Suppressor Genes, and Carcinogens.
AB  - The PIM proteins, which were initially discovered as proviral insertion sites in
      Moloney-murine leukemia virus infection, are a family of highly homologous
      serine/threonine kinases that have been reported to be overexpressed in
      hematological malignancies and solid tumors. The PIM proteins have also been
      associated with metastasis and overall treatment responses and implicated in the
      regulation of apoptosis, metabolism, the cell cycle, and homing and migration,
      which makes these proteins interesting targets for anti-cancer drug discovery.
      The use of retroviral insertional mutagenesis and refined approaches such as
      complementation tagging has allowed the identification of myc, pim, and a third
      group of genes (including bmi1 and gfi1) as complementing genes in
      lymphomagenesis. Moreover, mouse modeling of human cancer has provided an
      understanding of the molecular pathways that are involved in tumor initiation and
      progression at the physiological level. In particular, genetically modified mice
      have allowed researchers to further elucidate the role of each of the Pim
      isoforms in various tumor types. PIM kinases have been identified as weak
      oncogenes because experimental overexpression in lymphoid tissue, prostate, and
      liver induces tumors at a relatively low incidence and with a long latency.
      However, very strong synergistic tumorigenicity between Pim1/2 and c-Myc and
      other oncogenes has been observed in lymphoid tissues. Mouse models have also
      been used to study whether the inhibition of specific PIM isoforms is required to
      prevent carcinogen-induced sarcomas, indicating that the absence of Pim2 and Pim3
      greatly reduces sarcoma growth and bone invasion; the extent of this effect is
      similar to that observed in the absence of all three isoforms. This review will
      summarize some of the animal models that have been used to understand the isoform
      specific contribution of PIM kinases to tumorigenesis. 

PMID- 24860790
TI  - Pyrosequencing 16S rRNA genes of bacteria associated with wild tiger mosquito
      Aedes albopictus: a pilot study.
AB  - The Asian tiger mosquito Aedes (Stegomya) albopictus is an invasive species that
      has spread across the world in the last two decades, showing a great capacity to
      adapt to contrasting climates and environments. While demonstrated in many
      insects, the contribution of bacterial symbionts in Aedes ecology is a
      challenging aspect that needs to be investigated. Also some bacterial species
      have already been identified in Ae. albopictus using classical methods, but a
      more accurate survey of mosquito-associated bacterial diversity is needed to
      decipher the potential biological functions of bacterial symbionts in mediating
      or constraining insect adaptation. We surveyed the bacteria associated with field
      populations of Ae. albopictus from Madagascar by pyrosequencing 16S rRNA gene
      amplicons. Different aspects of amplicon preparation and sequencing depth were
      tested to optimize the breadth of bacterial diversity identified. The results
      revealed that all mosquitoes collected from different sites have a bacterial
      microbiota dominated by a single taxon, Wolbachia pipientis, which accounted for
      about 99% of all 92,615 sequences obtained. As Ae. albopictus is known to harbor
      two Wolbachia strains (wAlbA and wAlbB), a quantitative PCR was used to estimate
      the relative densities, (i.e., the bacteria-to-host gene ratios) of each strains
      in individual mosquitoes. Relative densities were between 6.25 * 10(0.01) and
      5.47 * 10(0.1) for wAlbA and between 2.03 * 10(0.1) and 1.4 * 10(1) for wAlbB.
      Apart from Wolbachia, a total of 31 bacterial taxa were identified at the genus
      level using different method variations. Diversity index values were low and
      probably underestimated the true diversity due to the high abundance of Wolbachia
      sequences vastly outnumbering sequences from other taxa. Further studies should
      implement alternative strategies to specifically discard from analysis any
      sequences from Wolbachia, the dominant endosymbiotic bacterium in Ae. albopictus
      from this area. 

PMID- 24860791
TI  - To be or not to be associated: power study of four statistical modeling
      approaches to identify parasite associations in cross-sectional studies.
AB  - A growing number of studies are reporting simultaneous infections by parasites in
      many different hosts. The detection of whether these parasites are significantly
      associated is important in medicine and epidemiology. Numerous approaches to
      detect associations are available, but only a few provide statistical tests.
      Furthermore, they generally test for an overall detection of association and do
      not identify which parasite is associated with which other one. Here, we
      developed a new approach, the association screening approach, to detect the
      overall and the detail of multi-parasite associations. We studied the power of
      this new approach and of three other known ones (i.e., the generalized chi
      square, the network and the multinomial GLM approaches) to identify parasite
      associations either due to parasite interactions or to confounding factors. We
      applied these four approaches to detect associations within two populations of
      multi-infected hosts: (1) rodents infected with Bartonella sp., Babesia microti
      and Anaplasma phagocytophilum and (2) bovine population infected with Theileria
      sp. and Babesia sp. We found that the best power is obtained with the screening
      model and the generalized chi-square test. The differentiation between
      associations, which are due to confounding factors and parasite interactions was
      not possible. The screening approach significantly identified associations
      between Bartonella doshiae and B. microti, and between T. parva, T. mutans, and
      T. velifera. Thus, the screening approach was relevant to test the overall
      presence of parasite associations and identify the parasite combinations that are
      significantly over- or under-represented. Unraveling whether the associations are
      due to real biological interactions or confounding factors should be further
      investigated. Nevertheless, in the age of genomics and the advent of new
      technologies, it is a considerable asset to speed up researches focusing on the
      mechanisms driving interactions between parasites. 

PMID- 24860793
TI  - Papillary carcinoma of the thyroglossal duct cyst: case report.
AB  - Thyroglossal duct cysts are the most common form of congenital cysts on the neck.
      The incidence of thyroid papillary carcinoma in thyroglossal duct cyst is less
      than 1%. In most cases the diagnosis is made postoperatively. We present a 22
      year-old female with thyroid papillary carcinoma arising from thyroglossal duct
      cyst,identified in pathologic study after sistrunk operation.In our case there
      was neither invasion to adjacent tissue nor lymph node involvement.The patient
      then underwent total thyroidectomy and bilateral neck dissection. The patient was
      treated with radioactive iodide and thyroid suppression therapy was given as
      adjuvant treatment.The patient has been following for two years without any
      metastasis.

PMID- 24860789
TI  - Attenuated Listeria monocytogenes: a powerful and versatile vector for the future
      of tumor immunotherapy.
AB  - For over a century, inactivated or attenuated bacteria have been employed in the
      clinic as immunotherapies to treat cancer, starting with the Coley's vaccines in
      the 19th century and leading to the currently approved bacillus Calmette-Guerin
      vaccine for bladder cancer. While effective, the inflammation induced by these
      therapies is transient and not designed to induce long-lasting tumor-specific
      cytolytic T lymphocyte (CTL) responses that have proven so adept at eradicating
      tumors. Therefore, in order to maintain the benefits of bacteria-induced acute
      inflammation but gain long-lasting anti-tumor immunity, many groups have
      constructed recombinant bacteria expressing tumor-associated antigens (TAAs) for
      the purpose of activating tumor-specific CTLs. One bacterium has proven
      particularly adept at inducing powerful anti-tumor immunity, Listeria
      monocytogenes (Lm). Lm is a gram-positive bacterium that selectively infects
      antigen-presenting cells wherein it is able to efficiently deliver tumor antigens
      to both the MHC Class I and II antigen presentation pathways for activation of
      tumor-targeting CTL-mediated immunity. Lm is a versatile bacterial vector as
      evidenced by its ability to induce therapeutic immunity against a wide-array of
      TAAs and specifically infect and kill tumor cells directly. It is for these
      reasons, among others, that Lm-based immunotherapies have delivered impressive
      therapeutic efficacy in preclinical models of cancer for two decades and are now
      showing promise clinically. In this review, we will provide an overview of the
      history leading up to the development of current Lm-based immunotherapies, the
      advantages and mechanisms of Lm as a therapeutic vaccine vector, the preclinical
      experience with Lm-based immunotherapies targeting a number of malignancies, and
      the recent findings from clinical trials along with concluding remarks on the
      future of Lm-based tumor immunotherapies. 

PMID- 24860792
TI  - Deletion of relA abrogates the capacity of Mycobacterium avium paratuberculosis
      to establish an infection in calves.
AB  - Previous comparative studies in goats revealed deletion of relA but not pknG
      abrogates the capacity of Mycobacterium avium subsp. paratuberculosis (Map) to
      establish a persistent infection. The immune response elicited by the mutant
      cleared infection. The objective of the present study was to extend the studies
      in calves and compare the proliferative response elicited by the relA deletion
      mutant (DeltarelA) and Map using flow cytometry and quantitative reverse
      transcription real-time PCR (qRT-PCR). Six 3-day-old calves were divided into two
      groups. Three were vaccinated with DeltarelA and 3 inoculated with wild type Map.
      The calves were challenged with Map 1 month later and necropsied 3 months post
      challenge. Three untreated calves were used as uninfected controls. Examination
      of tissues revealed the DeltarelA mutant was immune eliminated. Bacterial load of
      Map was significantly reduced in the calves vaccinated with DeltarelA and
      challenged with Map in comparison with calves inoculated and challenged with Map.
      A vigorous CD4 memory T cell response was detected at necropsy in PBMC from both
      infected groups. CD8 positive NK cells proliferated in the presence and absence
      of antigen stimulation in both treated groups but not in the uninfected group.
      IFN-gamma, IL17, and IL22 gene expression were up-regulated with an associated
      increase in their transcription factors, Tbet and RORC, in both treated groups.
      TGF-beta, IL-10, and FoxP3 were not up-regulated, indicating no activation of
      regulatory T cells. The findings show that the immune response to DeltarelA is
      clearly different than the response to Map. Understanding the immunological basis
      for this difference should facilitate development of a vaccine that elicits
      sterile immunity. 

PMID- 24860794
TI  - Prevalence of metabolic syndrome and its correlated factors among children and
      adolescents of Ahvaz aged 10 - 19.
AB  - BACKGROUND: Population-based studies for prevalence of metabolic syndrome (M.S)
      in children and adolescents are relatively rare. The aim of this study was to
      assess the Prevalence of M.S and correlated factors among children and
      adolescents aged 10 to 19 years in Ahvaz. METHODS: In this descriptive-analytical
      population- based study, 2246 children and adolescents, 10-19 years old (1113
      male and 1133 female) in Ahvaz, were evaluated. Anthropometry, biochemical
      measurement and blood pressure (BP) were assessed. Modified ATP III criteria 2005
      were used for M.S. definition. Center for disease and Control preventions (CDC)
      percentile were applied to define cut off points of waist circumference and BP.
      RESULTS: Prevalence of M.S. was 9% (95% CI: 8-10%) with prevalence in male 11%
      (95% CI: 10-12%) and female 7% (95% CI 6-8%). Among individuals with M.S,
      triglyceride (TG) and decreased high density lipoprotein (HDL) cholesterol levels
      were the most common components (33.5% and 24.1%, respectively). Prevalence of
      M.S was higher in overweight persons comparing to participants with at risk and
      normal weight group (in male: 24.1%, 14.3% and 9.9% respectively P = 0.0001), (in
      female: 22.6%, 18.3% and 4.5% respectively P = 0.0001). Among the correlated
      factors of M.S age (P = 0.0006), sex and BMI (P = 0.0001) had significant
      differences between subjects with and without M.S. whereas there was no
      significant difference between two groups in ethnicity, history of breast fed,
      birth weight neonatal ICU admission, maternal history(GDM, gestational HTN,
      Parity) and family history of HTN, obesity and DM (P > 0.05). CONCLUSION: This
      study shows high prevalence of M.S in Children and Adolescents in south west of
      Iran (Ahvaz) especially in overweight persons.

PMID- 24860795
TI  - Predictive factors of diabetic complications: a possible link between family
      history of diabetes and diabetic retinopathy.
AB  - BACKGROUND: The aim of this study was assessment of predictive factors of
      diabetic retinopathy. METHODS: A cross-sectional study was designed by recruiting
      1228 type 2 diabetic patients from a diabetes referral clinic over a six-month
      period (from July to December, 2012). Diabetes risk factors, complications,
      laboratory results have been recorded. RESULTS: Of the 1228 diabetic patients
      (54% women, mean age 58.48 +/- 9.94 years), prevalence of diabetes retinopathy
      was 26.6%. There were significant associations between retinopathy and family
      history of diabetes (p = 0.04), hypertension (p = 0.0001), diabetic duration (p =
      0.0001), poor glycemic control (p = 0.0001) and age of onset of diabetes (p =
      0.0001). However, no significant associations were found between retinopathy with
      dyslipidemia and obesity. In logistic regression model, poor glycemic control (p
      = 0.014), hypertension (p = 0.0001), duration of diabetes (p = 0.0001) and family
      history of diabetes (p = 0.012) independently predicted retinopathy after
      adjustment for age and sex. CONCLUSIONS: Diabetic complications are resulting
      from an interaction from genes and environmental factors. A family history of
      diabetes is pointing toward a possible genetic and epigenetic basis for diabetic
      retinopathy. Our findings suggest the role of epigenetic modifications and
      metabolic memory in diabetic retinopathy in subjects with family history of
      diabetes.

PMID- 24860796
TI  - The Theranostic Path to Personalized Nanomedicine.
AB  - Advances in nanotechnology and chemical engineering have led to the development
      of many different drug delivery systems. These 1-100(0) nm-sized carrier
      materials aim to increase drug concentrations at the pathological site, while
      avoiding their accumulation in healthy non-target tissues, thereby improving the
      balance between the efficacy and the toxicity of systemic (chemo-) therapeutic
      interventions. An important advantage of such nanocarrier materials is the ease
      of incorporating both diagnostic and therapeutic entities within a single
      formulation, enabling them to be used for theranostic purposes. We here describe
      the basic principles of using nanomaterials for targeting therapeutic and
      diagnostic agents to pathological sites, and we discuss how nanotheranostics and
      image-guided drug delivery can be used to personalize nanomedicine treatments.

PMID- 24860798
TI  - Total preputial flap: a reliable and versatile technique for urethral and penile
      reconstruction.
AB  - We revisit the technique of total preputial flap (TPF) and its application for
      urethroplasty, penile skin coverage of both and present our results in 43
      patients (41 hypospadias, 2 epispadias). There were no instances of flap
      necrosis. In patients without prior attempts at reconstruction (n = 36), we
      observed four urethrocutaneous fistulas. TPF allowed the repair of cases of
      proximal hypospadias in one stage with an acceptable complication rate. 

PMID- 24860797
TI  - Epigenetic modifications in pediatric acute lymphoblastic leukemia.
AB  - Aberrant epigenetic modifications are well-recognized drivers for oncogenesis.
      Pediatric acute lymphoblastic leukemia (ALL) is no exception and serves as a
      model toward the significant impact these heritable alterations can have in
      leukemogenesis. In this brief review, we will focus on the main aspects of
      epigenetics, which control leukemogenesis in pediatric ALL, mainly DNA
      methylation, histone modification, and microRNA alterations. As we continue to
      gain better understanding of the driving mechanisms for pediatric ALL at both
      diagnosis and relapse, therapeutic interventions directed toward these pathways
      and mechanisms can be harnessed and introduced into clinical trials for pediatric
      ALL. 

PMID- 24860801
TI  - Basic research opportunities focused on bio-based and bio-inspired materials and
      potential applications.

PMID- 24860800
TI  - Controlling topological entanglement in engineered protein hydrogels with a
      variety of thiol coupling chemistries.
AB  - Topological entanglements between polymer chains are achieved in associating
      protein hydrogels through the synthesis of high molecular weight proteins via
      chain extension using a variety of thiol coupling chemistries, including
      disulfide formation, thiol-maleimide, thiol-bromomaleimide and thiol-ene.
      Coupling of cysteines via disulfide formation results in the most pronounced
      entanglement effect in hydrogels, while other chemistries provide versatile means
      of changing the extent of entanglement, achieving faster chain extension, and
      providing a facile method of controlling the network hierarchy and incorporating
      stimuli responsivities. The addition of trifunctional coupling agents causes
      incomplete crosslinking and introduces branching architecture to the protein
      molecules. The high-frequency plateau modulus and the entanglement plateau
      modulus can be tuned by changing the ratio of difunctional chain extender to the
      trifunctional branching unit. Therefore, these chain extension reactions show
      promise in delicately controlling the relaxation and mechanical properties of
      engineered protein hydrogels in ways that complement their design through genetic
      engineering. 

PMID- 24860799
TI  - Potential for increased photosynthetic performance and crop productivity in
      response to climate change: role of CBFs and gibberellic acid.
AB  - We propose that targeting the enhanced photosynthetic performance associated with
      the cold acclimation of winter cultivars of rye (Secale cereale L.), wheat
      (Triticum aestivum L.), and Brassica napus L. may provide a novel approach to
      improve crop productivity under abiotic as well as biotic stress conditions. In
      support of this hypothesis, we provide the physiological, biochemical, and
      molecular evidence that the dwarf phenotype induced by cold acclimation is
      coupled to significant enhancement in photosynthetic performance, resistance to
      photoinhibition, and a decreased dependence on photoprotection through non
      photochemical quenching which result in enhanced biomass production and
      ultimately increased seed yield. These system-wide changes at the levels of
      phenotype, physiology, and biochemistry appear to be governed by the family of C
      repeat/dehydration-responsive family of transcription factors (CBF/DREB1). We
      relate this phenomenon to the semi-dwarf, gibberellic acid insensitive (GAI),
      cereal varieties developed during the "green revolution" of the early 1960s and
      1970s. We suggest that genetic manipulation of the family of C-repeat/dehydration
      responsive element binding transcription factors (CBF/DREB1) may provide a novel
      approach for the maintenance and perhaps even the enhancement of plant
      productivity under conditions of sub-optimal growth conditions predicted for our
      future climate. 

PMID- 24860802
TI  - Thermodynamics of water sorption in high performance glassy thermoplastic
      polymers.
AB  - Sorption thermodynamics of water in two glassy polymers, polyetherimide (PEI) and
      polyetheretherketone (PEEK), is investigated by coupling gravimetry and on line
      FTIR spectroscopy in order to gather information on the total amount of sorbed
      water as well as on the different species of water molecules absorbed within the
      polymers, addressing the issue of cross- and self-interactions occurring in the
      polymer/water systems. Water sorption isotherms have been determined at
      temperatures ranging from 30 to 70 degrees C while FTIR spectroscopy has been
      performed only at 30 degrees C. The experimental analysis provided information on
      the groups present on the polymer backbones involved in hydrogen bonding
      interactions with absorbed water molecules. Moreover, it also supplied
      qualitative indications about the different "populations" of water molecules
      present within the PEEK and a quantitative assessment of these "populations" in
      the case of PEI. The results of the experimental analysis have been interpreted
      using an equation of state theory based on a compressible lattice fluid model for
      the Gibbs energy of the polymer-water mixture, developed by extending to the case
      of out of equilibrium glassy polymers a previous model intended for equilibrium
      rubbery polymers. The model accounts for the non-equilibrium nature of glassy
      polymers as well as for mean field and for hydrogen bonding interactions,
      providing a satisfactory quantitative interpretation of the experimental data. 

PMID- 24860803
TI  - Alternative methods of processing bio-feedstocks in formulated consumer product
      design.
AB  - In this work new methods of processing bio-feedstocks in the formulated consumer
      products industry are discussed. Our current approach to formulated products
      design is based on heuristic knowledge of formulators that allows selecting
      individual compounds from a library of available materials with known properties.
      We speculate that most of the compounds (or functions) that make up the product
      to be designed can potentially be obtained from a few bio-sources. In this case,
      it may be possible to design a sequence of transformations required to convert
      feedstocks into products with desired properties, analogous to a metabolic
      pathway of a complex organism. We conceptualize some novel approaches to
      processing bio-feedstocks with the aim of bypassing the step of a fixed library
      of ingredients. Two approaches are brought forward: one making use of knowledge
      based expert systems and the other making use of applications of metabolic
      engineering and dynamic combinatorial chemistry. 

PMID- 24860805
TI  - Upregulated PD-1 Expression Is Associated with the Development of Systemic Lupus
      Erythematosus, but Not the PD-1.1 Allele of the PDCD1 Gene.
AB  - Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with
      complicated genetic inheritance. Programmed death 1 (PD-1), a negative T cell
      regulator to maintain peripheral tolerance, induces negative signals to T cells
      during interaction with its ligands and is therefore a candidate gene in the
      development of SLE. In order to examine whether expression levels of PD-1
      contribute to the pathogenesis of SLE, 30 patients with SLE and 30 controls were
      recruited and their PD-1 expression levels in peripheral blood mononuclear cells
      (PBMCs) were measured via flow cytometry and quantitative real-time-reverse
      transcription polymerase chain reaction (RT-PCR). Also, whether PD-1 expression
      levels are associated with the variant of the SNP rs36084323 and the SLE Disease
      Activity Index (SLEDAI) was studied in this work. The PD-1 expression levels of
      SLE patients were significantly increased compared with those of the healthy
      controls. The upregulated PD-1 expression levels in SLE patients were greatly
      associated with SLEDAI scores. No significant difference was found between PD-1
      expression levels and SNP rs36084323. The results suggest that increased
      expression of PD-1 may correlate with the pathogenesis of SLE, upregulated PD-1
      expression may be a biomarker for SLE diagnosis, and PD-1 inhibitor may be useful
      to SLE treatment. 

PMID- 24860806
TI  - A retrospective study of ectoparasitosis in patients referred to Imam Reza
      Hospital of Mashhad, Iran.
AB  - This cross-sectional study was performed on all patients suspected to be
      suffering from ectoparasites who were referred to the parasitology laboratory of
      Imam Reza Hospital of Mashhad during 15 years (April 1995 to April 2010). All
      patients' data were collected from the questionnaires and then analyzed
      statistically. From 1814 suspected patients to be suffering from ectoparasites,
      375 patients had scabies and, 99 suffer from pediculosis. The mean age of
      patients was 26/18 +/- 17/68. The most common age of scabies was 10-19 (27/7%)
      and pediculosis 0-9(9/6%) (P value = 0.00). The highest incidence of pediculosis
      was in women (3.6%) and scabies in men (13.7%) (P value = 0.00). Pediculosis is
      more common in children (9/9%) and scabies in workers (32%)(P value = 0.00).
      Scabies and pediculosis were more prevalent in patients from Razavi Khorasan
      Province with 18.7% and 5%, respectively (P value = 0.08). 

PMID- 24860804
TI  - Instrumentation in Diffuse Optical Imaging.
AB  - Diffuse optical imaging is highly versatile and has a very broad range of
      applications in biology and medicine. It covers diffuse optical tomography,
      fluorescence diffuse optical tomography, bioluminescence, and a number of other
      new imaging methods. These methods of diffuse optical imaging have diversified
      instrument configurations but share the same core physical principle - light
      propagation in highly diffusive media, i.e., the biological tissue. In this
      review, the author summarizes the latest development in instrumentation and
      methodology available to diffuse optical imaging in terms of system architecture,
      light source, photo-detection, spectral separation, signal modulation, and lastly
      imaging contrast.

PMID- 24860807
TI  - Effects of cyhalothrin-based pesticide on early life stages of common carp
      (Cyprinus carpio L.).
AB  - The effects of Nexide (a.i. gamma-cyhalothrin 60 g L(-1)) on cumulative
      mortality, growth indices, and ontogenetic development of embryos and larvae of
      common carp (Cyprinus carpio L.) were studied. Levels of oxidative stress
      parameters glutathione reductase (GR), glutathione peroxidase (GPx), catalase
      (CAT), glutathione-S-transferase (GST), and lipid peroxidation were determined.
      Eggs of newly fertilised common carp were exposed to Nexide at concentrations 5,
      25, 50, 100, and 250  MU g L(-1) (0.3, 1.5, 3, 6, and 15  MU g L(-1) gamma
      cyhalothrin). All organisms exposed to concentrations higher than 50  MU g L(-1)
      died soon after hatching; at 25  MU g L(-1), 95% mortality was recorded. Larvae
      exposed to 5  MU g L(-1) showed significantly lower growth and retarded
      ontogenetic development compared to control. Histological examination of the
      livers of larvae from the exposed group revealed dystrophic changes. The value of
      detoxification enzyme GST of organisms from the exposed group was significantly
      higher compared to the control and the value of defensive enzyme GPx was
      significantly lower compared to the control. The results of our investigation
      confirmed that contamination of aquatic environment by pesticides containing
      cyhalothrin may impair growth and development of early life stages of carp and
      cause disbalance of defensive enzymes. 

PMID- 24860809
TI  - Haemodynamic monitoring in the intensive care unit: results from a web-based
      Swiss survey.
AB  - BACKGROUND: The aim of this survey was to describe, in a situation of growing
      availability of monitoring devices and parameters, the practices in haemodynamic
      monitoring at the bedside. METHODS: We conducted a Web-based survey in Swiss
      adult ICUs (2009-2010). The questionnaire explored the kind of monitoring used
      and how the fluid management was addressed. RESULTS: Our survey included 71% of
      Swiss ICUs. Echocardiography (95%), pulmonary artery catheter (PAC: 85%), and
      transpulmonary thermodilution (TPTD) (82%) were the most commonly used. TPTD and
      PAC were frequently both available, although TPTD was the preferred technique.
      Echocardiography was widely available (95%) but seems to be rarely performed by
      intensivists themselves. Guidelines for the management of fluid infusion were
      available in 45% of ICUs. For the prediction of fluid responsiveness,
      intensivists rely preferentially on dynamic indices or echocardiographic
      parameters, but static parameters, such as central venous pressure or pulmonary
      artery occlusion pressure, were still used. CONCLUSIONS: In most Swiss ICUs,
      multiple haemodynamic monitoring devices are available, although TPTD is most
      commonly used. Despite the usefulness of echocardiography and its large
      availability, it is not widely performed by Swiss intensivists themselves.
      Regarding fluid management, several parameters are used without a clear consensus
      for the optimal method.

PMID- 24860811
TI  - Coastal biotechnology: facing the global and the regional changes.

PMID- 24860810
TI  - Morphometric and statistical analysis of the palmaris longus muscle in human and
      non-human primates.
AB  - The palmaris longus is considered a phylogenetic degenerate metacarpophalangeal
      joint flexor muscle in humans, a small vestigial forearm muscle; it is the most
      variable muscle in humans, showing variation in position, duplication, slips and
      could be reverted. It is frequently studied in papers about human anatomical
      variations in cadavers and in vivo, its variation has importance in medical
      clinic, surgery, radiological analysis, in studies about high-performance
      athletes, in genetics and anthropologic studies. Most studies about palmaris
      longus in humans are associated to frequency or case studies, but comparative
      anatomy in primates and comparative morphometry were not found in scientific
      literature. Comparative anatomy associated to morphometry of palmaris longus
      could explain the degeneration observed in this muscle in two of three of the
      great apes. Hypothetically, the comparison of the relative length of tendons and
      belly could indicate the pathway of the degeneration of this muscle, that is, the
      degeneration could be associated to increased tendon length and decreased belly
      from more primitive primates to those most derivate, that is, great apes to
      modern humans. In conclusion, in primates, the tendon of the palmaris longus
      increase from Lemuriformes to modern humans, that is, from arboreal to
      terrestrial primates and the muscle became weaker and tending to be missing. 

PMID- 24860808
TI  - Entamoeba histolytica and E. dispar Calreticulin: inhibition of classical
      complement pathway and differences in the level of expression in amoebic liver
      abscess.
AB  - The role of calreticulin (CRT) in host-parasite interactions has recently become
      an important area of research. Information about the functions of calreticulin
      and its relevance to the physiology of Entamoeba parasites is limited. The
      present work demonstrates that CRT of both pathogenic E. histolytica and
      nonpathogenic E. dispar species specifically interacted with human C1q inhibiting
      the activation of the classical complement pathway. Using recombinant EhCRT
      protein, we demonstrate that CRT interaction site and human C1q is located at the
      N-terminal region of EhCRT. The immunofluorescence and confocal microscopy
      experiments show that CRT and human C1q colocalize in the cytoplasmic vesicles
      and near to the surface membrane of previously permeabilized trophozoites or are
      incubated with normal human serum which is known to destroy trophozoites. In the
      presence of peripheral mononuclear blood cells, the distribution of EhCRT and C1q
      is clearly over the surface membrane of trophozoites. Nevertheless, the level of
      expression of CRT in situ in lesions of amoebic liver abscess (ALA) in the
      hamster model is different in both Entamoeba species; this molecule is expressed
      in higher levels in E. histolytica than in E. dispar. This result suggests that
      EhCRT may modulate some functions during the early moments of the host-parasite
      relationship. 

PMID- 24860812
TI  - Anticancer drug-incorporated layered double hydroxide nanohybrids and their
      enhanced anticancer therapeutic efficacy in combination cancer treatment.
AB  - OBJECTIVE: Layered double hydroxide (LDH) nanoparticles have been studied as
      cellular delivery carriers for anionic anticancer agents. As MTX and 5-FU are
      clinically utilized anticancer drugs in combination therapy, we aimed to enhance
      the therapeutic performance with the help of LDH nanoparticles. METHOD:
      Anticancer drugs, MTX and 5-FU, and their combination, were incorporated into LDH
      by reconstruction method. Simply, LDHs were thermally pretreated at 400 degrees
      C, and then reacted with drug solution to simultaneously form drug-incorporated
      LDH. Thus prepared MTX/LDH (ML), 5-FU/LDH (FL), and (MTX + 5-FU)/LDH (MFL)
      nanohybrids were characterized by X-ray diffractometer, scanning electron
      microscopy, infrared spectroscopy, thermal analysis, zeta potential measurement,
      dynamic light scattering, and so forth. The nanohybrids were administrated to the
      human cervical adenocarcinoma, HeLa cells, in concentration-dependent manner,
      comparing with drug itself to verify the enhanced therapeutic efficacy.
      CONCLUSION: All the nanohybrids successfully accommodated intended drug molecules
      in their house-of-card-like structures during reconstruction reaction. It was
      found that the anticancer efficacy of MFL nanohybrid was higher than other
      nanohybrids, free drugs, or their mixtures, which means the multidrug
      incorporated LDH nanohybrids could be potential drug delivery carriers for
      efficient cancer treatment via combination therapy.

PMID- 24860813
TI  - Early monitoring antiangiogenesis treatment response of Sunitinib in U87MG Tumor
      Xenograft by (18)F-FLT MicroPET/CT imaging.
AB  - AIM: It was aimed to monitor early treatment response of Sunitinib in U87MG
      models mimicking glioblastoma multiforme by longitudinal (18)F-FLT microPET/CT
      imaging in this study. METHODS: U87MG tumor mice were intragastrically injected
      with Sunitinib at a dose of 80 mg/kg for consecutive 7 days. (18)F-FLT
      microPET/CT scans were acquired on days 0, 1, 3, 7, and 13 after therapy. Tumor
      sizes and body weight were measured. Tumor samples were collected for
      immunohistochemical analysis of proliferation and microvessel density (MVD) with
      anti-Ki67 and anti-CD31, respectively. RESULTS: The uptake ratios of tumor to the
      contralateral muscle (T/M) of (18)F-FLT in the Sunitinib group decreased from
      baseline to day 3 (T/M0 = 2.98 +/- 0.33; T/M3 = 2.23 +/- 0.36; P < 0.001),
      reached the bottom on day 7 (T/M7 = 1.96 +/- 0.35; P < 0.001), and then recovered
      on day 13. The T/M of (18)F-FLT uptake in the control group remained around 3.0.
      There was no difference for the tumor size between both groups until day 11.
      (18)F-FLT uptakes of tumor were correlated with Ki67 staining index and MVD.
      CONCLUSION: Early therapy response to Sunitinib could be predicted via (18)F-FLT
      PET, which will contribute to monitoring antiangiogenesis treatment.

PMID- 24860815
TI  - Smoking habits among italian adolescents: what has changed in the last decade?
AB  - Tobacco use, alcohol abuse, overweight and obesity are risk factors for numerous
      diseases in Italy as elsewhere. However, children and adolescents are not usually
      included in official national surveys although it is at this stage of life when
      unhealthy habits are often established. Italian participation in HBSC and GYTS
      surveys allows our country to implement standardized surveillance systems
      providing reliable information on tobacco-related behaviors of this population.
      Data from three HBSC surveys (2002-2010) show that following the drop in the
      first half of the decade, prevalence of tobacco use stabilized in the second
      half. The decline was significant for younger age groups, while prevalence of
      regular tobacco use remained stable among 15-year-olds. Many adolescents reported
      being exposed to secondhand smoke, to have at least one parent who smokes, and
      having seen teachers and students smoking at school. Although the sale of tobacco
      products to minors is prohibited, the vast majority had no trouble in buying
      cigarettes. Data from GYTS and HBSC surveys provide a wealth of information about
      attitudes and behaviors of Italian adolescents with respect to smoking. Despite
      some progress, sizeable gaps remain in meeting standard recommendations for
      discouraging smoking initiation and motivating adolescent smokers to quit the
      habit. 

PMID- 24860816
TI  - The influence of BMX gene polymorphisms on clinical symptoms after mild traumatic
      brain injury.
AB  - Mild traumatic brain injury (mTBI) is one of the most common neurological
      disorders. Most patients diagnosed with mTBI could fully recover, but 15% of
      patients suffer from persistent symptoms. In recent studies, genetic factors were
      found to be associated with recovery and clinical outcomes after TBI. In
      addition, results from our previous research have demonstrated that the bone
      marrow tyrosine kinase gene in chromosome X (BMX), a member of the Tec family of
      kinases, is highly expressed in rats with TBI. Therefore, our aim in this study
      was to identify the association between genetic polymorphisms of BMX and clinical
      symptoms following mTBI. Four tagging single nucleotide polymorphisms (tSNPs) of
      BMX with minimum allele frequency (MAF) >1% were selected from the HapMap Han
      Chinese database. Among these polymorphisms, rs16979956 was found to be
      associated with the Beck anxiety inventory (BAI) and dizziness handicap inventory
      (DHI) scores within the first week after head injury. Additionally, another SNP,
      rs35697037, showed a significant correlation with dizziness symptoms. These
      findings suggested that polymorphisms of the BMX gene could be a potential
      predictor of clinical symptoms following mTBI. 

PMID- 24860817
TI  - Augmenting multi-instance multilabel learning with sparse bayesian models for
      skin biopsy image analysis.
AB  - Skin biopsy images can reveal causes and severity of many skin diseases, which is
      a significant complement for skin surface inspection. Automatic annotation of
      skin biopsy image is an important problem for increasing efficiency and reducing
      the subjectiveness in diagnosis. However it is challenging particularly when
      there exists indirect relationship between annotation terms and local regions of
      a biopsy image, as well as local structures with different textures. In this
      paper, a novel method based on a recent proposed machine learning model, named
      multi-instance multilabel (MIML), is proposed to model the potential knowledge
      and experience of doctors on skin biopsy image annotation. We first show that the
      problem of skin biopsy image annotation can naturally be expressed as a MIML
      problem and then propose an image representation method that can capture both
      region structure and texture features, and a sparse Bayesian MIML algorithm which
      can produce probabilities indicating the confidence of annotation. The proposed
      algorithm framework is evaluated on a real clinical dataset containing 12,700
      skin biopsy images. The results show that it is effective and prominent. 

PMID- 24860818
TI  - Lentiviral protein transduction with genome-modifying HIV-1 integrase-I-PpoI
      fusion proteins: studies on specificity and cytotoxicity.
AB  - Rare-cutting endonucleases, such as the I-PpoI, can be used for the induction of
      double strand breaks (DSBs) in genome editing and targeted integration based on
      homologous recombination. For therapeutic approaches, the specificity and the
      pattern of off-target effects are of high importance in these techniques. For its
      applications, the endonuclease needs to be transported into the target cell
      nucleus, where the mechanism of transport may affect its function. Here, we have
      studied the lentiviral protein transduction of the integrase (IN)-PpoI fusion
      protein using the cis-packaging method. In genome-wide interaction studies, IN
      fusion proteins were verified to bind their target sequence containing 28S
      ribosomal RNA (rRNA) genes with a 100-fold enrichment, despite the well
      documented behavior of IN to be tethered into various genomic areas by host-cell
      factors. In addition, to estimate the applicability of the method, DSB-induced
      cytotoxic effects with different vector endonuclease configurations were studied
      in a panel of cells. Varying the amount and activity of endonuclease enabled the
      adjustment of ratio between the induced DSBs and transported DNA. In cell
      studies, certain cancerous cell lines were especially prone to DSBs in rRNA
      genes, which led us to test the protein transduction in a tumour environment in
      an in vivo study. In summary, the results highlight the potential of lentiviral
      vectors (LVVs) for the nuclear delivery of endonucleases. 

PMID- 24860814
TI  - Association between risk factors for vascular dementia and adiponectin.
AB  - Vascular dementia is caused by various factors, including increased age,
      diabetes, hypertension, atherosclerosis, and stroke. Adiponectin is an adipokine
      secreted by adipose tissue. Adiponectin is widely known as a regulating factor
      related to cardiovascular disease and diabetes. Adiponectin plasma levels
      decrease with age. Decreased adiponectin increases the risk of cardiovascular
      disease and diabetes. Adiponectin improves hypertension and atherosclerosis by
      acting as a vasodilator and antiatherogenic factor. Moreover, adiponectin is
      involved in cognitive dysfunction via modulation of insulin signal transduction
      in the brain. Case-control studies demonstrate the association between low
      adiponectin and increased risk of stroke, hypertension, and diabetes. This review
      summarizes the recent findings on the association between risk factors for
      vascular dementia and adiponectin. To emphasize this relationship, we will
      discuss the importance of research regarding the role of adiponectin in vascular
      dementia. 

PMID- 24860819
TI  - Association between two common polymorphisms and risk of hepatocellular
      carcinoma: evidence from an updated meta-analysis.
AB  - BACKGROUND: Recent studies suggested that two common polymorphisms, miR-146a G>C
      and miR-196a2 C>T, may be associated with individual susceptibility to
      hepatocellular carcinoma (HCC). However, the results remain conflicting rather
      than conclusive. Object. The aim of this study was to assess the association
      between miR-146a G>C and miR-196a2 C>T polymorphisms and the risk of HCC.
      METHODS: A meta-analysis of 17 studies (10938 cases and 11967 controls) was
      performed. Odds ratios and 95% confidence intervals were used to evaluate the
      strength of the association. RESULTS: For miR-146a G>C, the variant genotypes
      were associated with a decreased risk of HCC (CC versus GG: OR = 0.780 and 95% CI
      0.700-0.869; GC/CC versus GG: OR = 0.865 and 95% CI 0.787-0.952; CC versus GC/GG:
      OR = 0.835 and 95% CI 0.774-0.901). For miR-196a2 C>T, significant association
      was also observed (TT versus CC: OR = 0.783, 95% CI: 0.649-0.943, and P = 0.010;
      CT versus CC: OR = 0.831, 95% CI 0.714-0.967, and P = 0.017; CT/TT versus CC: OR
      = 0.817, 95% CI 0.703-0.949, and P = 0.008). CONCLUSION: The two common
      polymorphisms miR-146a G>C and miR-196a2 C>T were associated with decreased HCC
      susceptibility, especially in Asian population.

PMID- 24860820
TI  - Libidibia ferrea mature seeds promote antinociceptive effect by peripheral and
      central pathway: possible involvement of opioid and cholinergic receptors.
AB  - Libidibia ferrea (LF) is a medicinal plant that holds many pharmacological
      properties. We evaluated the antinociceptive effect in the LF aqueous seed
      extract and Lipidic Portion of Libidibia ferrea (LPLF), partially elucidating
      their mechanisms. Histochemical tests and Gas chromatography of the LPLF were
      performed to characterize its fatty acids. Acetic acid-induced abdominal
      constriction, formalin-induced pain, and hot-plate test in mice were employed in
      the study. In all experiments, aqueous extract or LPLF was administered
      systemically at the doses of 1, 5, and 10 mg/kg. LF aqueous seed extract and LPLF
      demonstrated a dose-dependent antinociceptive effect in all tests indicating both
      peripheral anti-inflammatory and central analgesia properties. Also, the use of
      atropine (5 mg/kg), naloxone (5 mg/kg) in the abdominal writhing test was able to
      reverse the antinociceptive effect of the LPLF, indicating that at least one of
      LF lipids components is responsible for the dose related antinociceptive action
      in chemical and thermal models of nociception in mice. Together, the present
      results suggested that Libidibia ferrea induced antinociceptive activity is
      possibly related to its ability to inhibit opioid, cholinergic receptors, and
      cyclooxygenase-2 pathway, since its main component, linoleic acid, has been
      demonstrated to produce such effect in previous studies. 

PMID- 24860822
TI  - Stability analysis of a high fibre yield and low lignin content "thick stem"
      mutant in tossa jute (Corchorus olitorius L.).
AB  - A "thick stem" mutant of Corchorus olitorius L. was induced at M2 (0.50%, 4 h,
      EMS) and the true breeding mutant is assessed across generations (M5 to M7)
      considering morphometric traits as well as SEM analysis of pollen grains and raw
      jute fibres, stem anatomy, cytogenetical attributes, and lignin content in
      relation to control. Furthermore, single fibre diameter and tensile strength are
      also analysed. The objective is to assess the stability of mutant for its
      effective exploration for raising a new plant type in tossa jute for commercial
      exploitation and efficient breeding. The mutant trait is monogenic recessive to
      normal. Results indicate that "thick stem" mutant is stable across generations
      (2n = 14) with distinctive high seed and fibre yield and significantly low lignin
      content. Stem anatomy of the mutant shows significant enhancement in fibre zone,
      number of fibre pyramids and fibre bundles per pyramid, and diameter of fibre
      cell in relation to control. Moreover, tensile strength of mutant fibre is
      significantly higher than control fibre and the trait is inversely related to
      fibre diameter. However the mutant is associated with low germination frequency,
      poor seed viability, and high pollen sterility, which may be eliminated through
      mutational approach followed by rigorous selection and efficient breeding. 

PMID- 24860821
TI  - Gender specific association of RAS gene polymorphism with essential hypertension:
      a case-control study.
AB  - Renin-angiotensin system (RAS) polymorphisms have been studied as candidate risk
      factors for hypertension with inconsistent results, possibly due to heterogeneity
      among various genetic and environmental factors. A case-control association study
      was conducted to investigate a possible involvement of polymorphisms of three RAS
      genes: AGT M235T (rs699), ACE I/D (rs4340) and G2350A (rs4343), and AGTR1 A1166C
      (rs5186) in essential hypertensive patients. A total of 211 cases and 211
      controls were recruited for this study. Genotyping was performed using PCR-RFLP
      method. The genotype and allele distribution of the M235T variant differed
      significantly in hypertensives and normotensives (OR-CI = 2.62 (1.24-5.76), P =
      0.006; OR-CI = 0.699 (0.518-0.943), P = 0.018), respectively. When the samples
      were segregated based on sex, the 235TT genotype and T allele were predominant in
      the female patients (OR-CI = 5.68 (1.60-25.10), P = 0.002; OR-CI = 0.522 (0.330
      0.826), P = 0.005) as compare to the male patients (OR-CI = 1.54 (1.24-5.76), P =
      0.34; OR-CI = 0.874 (0.330-0.826), P = 0.506), respectively. For ACE DD variant,
      we found overrepresentation of "I"-allele (homozygous II and heterozygous ID) in
      unaffected males which suggest its protective role in studied population (OR-CI =
      0.401 (0.224-0.718); P = 0.0009). The M235T variant of the AGT is significantly
      associated with female hypertensives and ACE DD variant could be a risk allele
      for essential hypertension in south India. 

PMID- 24860824
TI  - Production and characterization of a polyclonal antibody of anti-rLipL21-IgG
      against leptospira for early detection of acute leptospirosis.
AB  - Leptospirosis is one of the zoonotic diseases in animals and humans throughout
      the world. LipL21 is one of the important surface-exposed lipoproteins in
      leptospires and the most effective cross protective immunogenic antigen. It is
      widely considered as a diagnostic marker for leptospirosis. In this study, we
      evaluated the serodiagnostic potential of LipL21 protein of Leptospira
      interrogans serovar Pomona. We have successfully amplified, cloned, and expressed
      LipL21 in E. coli and evaluated its specificity by immunoblotting. Purified
      recombinant LipL21 (rLipL21) was inoculated into rabbits for the production of
      polyclonal antibody. Characterization of the purified IgG antibody against
      rLipL21 was performed by cross reactivity assay. Only sera from leptospirosis
      patients and rabbit hyperimmune sera recognized rLipL21 while the
      nonleptospirosis control sera showed no reaction in immunoblotting. We confirmed
      that anti-rLipL21-IgG antibody cross reacted with and detected only pathogenic
      leptospiral species and it did not react with nonpathogenic leptospires and other
      bacterial species. Results observed showed that anti-rLipL21-IgG antibody has
      high specificity and sensitivity to leptospires. The findings indicated that the
      antibody could be used in a diagnostic assay for detection of leptospires or
      their proteins in the early phase of infection. 

PMID- 24860823
TI  - Macrophage plasticity in skeletal muscle repair.
AB  - Macrophages are one of the first barriers of host defence against pathogens.
      Beyond their role in innate immunity, macrophages play increasingly defined roles
      in orchestrating the healing of various injured tissues. Perturbations of
      macrophage function and/or activation may result in impaired regeneration and
      fibrosis deposition as described in several chronic pathological diseases.
      Heterogeneity and plasticity have been demonstrated to be hallmarks of
      macrophages. In response to environmental cues they display a proinflammatory
      (M1) or an alternative anti-inflammatory (M2) phenotype. A lot of evidence
      demonstrated that after acute injury M1 macrophages infiltrate early to promote
      the clearance of necrotic debris, whereas M2 macrophages appear later to sustain
      tissue healing. Whether the sequential presence of two different macrophage
      populations results from a dynamic shift in macrophage polarization or from the
      recruitment of new circulating monocytes is a subject of ongoing debate. In this
      paper, we discuss the current available information about the role that different
      phenotypes of macrophages plays after injury and during the remodelling phase in
      different tissue types, with particular attention to the skeletal muscle. 

PMID- 24860825
TI  - Effect of dietary intake of avocado oil and olive oil on biochemical markers of
      liver function in sucrose-fed rats.
AB  - Metabolic changes, along with cardiovascular and hepatic factors, are associated
      with the development of diseases such as diabetes, dyslipidemia, and obesity. We
      evaluated the effect of avocado oil supplementation (centrifuged and solvent
      extracted), compared with olive oil, upon the hepatic function in sucrose-fed
      rats. Twenty-five rats were divided into five groups: control (basal diet), a
      sucrose-fed group (basal diet plus 30% sucrose solution), and three other groups
      (S-OO, S-AOC, and S-AOS, indicating basal diet plus 30% sucrose solution plus
      olive oil OO, avocado oil extracted by centrifugation AOC or using solvent AOS,
      resp.). Glucose, total cholesterol, triglycerides, total protein, albumin,
      globulin, direct bilirubin, glutamic pyruvic transaminase, glutamic oxaloacetic
      transaminase, alkaline phosphatase, cholinesterase, and alpha -amylase
      concentrations were determined and avocado oil effect on them was studied. In
      some cases the induced metabolic alteration significantly affected total protein
      and bilirubin levels and also had a highly significant effect on alpha -amylase
      levels. AOC and AOS exhibited effects similar to those of olive oil, according to
      the nonsignificant difference in fatty acid profile observed by other authors.
      Avocado oil consumption could be beneficial in the control of altered metabolic
      profile illnesses as it presents effects on hepatic function biochemical markers
      similar to olive oil. 

PMID- 24860826
TI  - Cerebral endothelial function determined by cerebrovascular reactivity to L
      arginine.
AB  - Endothelium forms the inner cellular lining of blood vessels and plays an
      important role in many physiological functions including the control of vasomotor
      tone. Cerebral endothelium is probably one of the most specific types but until
      recently it was impossible to determine its function. In this review, the role of
      cerebrovascular reactivity to L-arginine (CVR-L-Arg) for assessment of cerebral
      endothelial function is discussed. L-Arginine induces vasodilatation through
      enhanced production of nitric oxide (NO) in the cerebral endothelium.
      Transcranial Doppler sonography is used for evaluation of cerebral blood flow
      changes. The method is noninvasive, inexpensive, and enables reproducible
      measurements. CVR-L-Arg has been compared to flow-mediated dilatation as a gold
      standard for systemic endothelial function and intima-media thickness as a marker
      for morphological changes. However, it seems to show specific cerebral
      endothelial function. So far CVR-L-Arg has been used to study cerebral
      endothelial function in many pathological conditions such as stroke, migraine,
      etc. In addition CVR-L-Arg has also proven its usefulness in order to show
      potential improvement after pharmacological interventions. In conclusion CVR-L
      Arg is a promising noninvasive research method that could provide means for
      evaluation of cerebral endothelial function in physiological and pathological
      conditions. 

PMID- 24860827
TI  - Molecular analysis of ciprofloxacin resistance mechanisms in Malaysian ESBL
      producing Klebsiella pneumoniae isolates and development of mismatch
      amplification mutation assays (MAMA) for rapid detection of gyrA and parC
      mutations.
AB  - Ninety-three Malaysian extended-spectrum beta-lactamase (ESBL)-producing
      Klebsiella pneumoniae isolates were investigated for ciprofloxacin resistance.
      Two mismatch amplification mutation (MAMA) assays were developed and used to
      facilitate rapid detection of gyrA and parC mutations. The isolates were also
      screened for plasmid-mediated quinolone resistance (PMQR) genes including aac(6')
      Ib-cr, qepA, and qnr. Ciprofloxacin resistance (MICs 4- >= 32  MU g/mL) was noted
      in 34 (37%) isolates, of which 33 isolates had multiple mutations either in gyrA
      alone (n = 1) or in both gyrA and parC regions (n = 32). aac(6')-Ib-cr was the
      most common PMQR gene detected in this study (n = 61), followed by qnrB and qnrS
      (n = 55 and 1, resp.). Low-level ciprofloxacin resistance (MICs 1-2  MU g/mL) was
      noted in 40 (43%) isolates carrying qnrB accompanied by either aac(6')-Ib-cr (n =
      34) or a single gyrA 83 mutation (n = 6). Ciprofloxacin resistance was
      significantly associated with the presence of multiple mutations in gyrA and parC
      regions. While the isolates harbouring gyrA and/or parC alteration were
      distributed into 11 PFGE clusters, no specific clusters were associated with
      isolates carrying PMQR genes. The high prevalence of ciprofloxacin resistance
      amongst the Malaysian ESBL-producing K. pneumoniae isolates suggests the need for
      more effective infection control measures to limit the spread of these resistant
      organisms in the hospital. 

PMID- 24860828
TI  - Effect of curcumin on lifespan, activity pattern, oxidative stress, and apoptosis
      in the brains of transgenic Drosophila model of Parkinson's disease.
AB  - BACKGROUND: A time dependent loss of dopaminergic neurons and the formation of
      intracellular aggregates of alpha synuclein have been reported in PD model flies.
      METHODS: The progeny (PD flies) expressing human alpha synuclein was exposed to
      25, 50, and 100 uM of curcumin mixed in the diet for 24 days. The effect of
      curcumin was studied on lifespan, activity pattern, oxidative stress, and
      apoptosis in the brains of PD model flies. The activity of PD model flies was
      monitored by using Drosophila activity monitors (DAMs). For the estimation of
      oxidative stress, lipid peroxidation and protein carbonyl content were estimated
      in the flies brains of each treated groups. The cell death in Drosophila brain
      was analyzed by isolating brains in Ringer's solution placing them in 70% ethanol
      and stained in acridine orange to calculate the gray scale values. RESULTS: The
      exposure of flies to 25, 50, and 100 uM of curcumin showed a dose dependent
      significant delay in the loss of activity pattern, reduction in the oxidative
      stress and apoptosis, and increase in the life span of PD model flies.
      CONCLUSION: Curcumin is potent in reducing PD symptoms.

PMID- 24860830
TI  - Antitumor and antiangiogenic activities of curcumin in cervical cancer xenografts
      in nude mice.
AB  - To evaluate the effects of curcumin (CUR) on tumor progression and angiogenesis
      in cervical cancer- (CaSki-) implanted nude mice and on the angiogenic
      biomarkers: vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2),
      and epidermal growth factor receptor (EGFR). CaSki cells were subcutaneously
      injected in nude mice to establish subcutaneous tumors. One month after
      injection, mice were orally administered vehicle or 500, 1,000, and 1,500 mg/kg
      of CUR daily * 30 consecutive days. Tumor volume was measured every 3-4 days. At
      the end of the study, tumor microvasculature was observed under confocal
      microscope, and immunohistochemical analyses were performed to detect CD31, VEGF,
      COX-2, and EGFR. CUR at the doses of 1,000 and 1,500 mg/kg showed significant
      tumor growth retardation (21.03% and 35.57%) versus CaSki + vehicle group. The
      microvascular density (MVD) in CaSki + vehicle group was significantly increased
      versus Control + vehicle group and significantly reduced by CUR (1,000 and 1,500
      mg/kg). VEGF, COX-2, and EGFR expressions were upregulated in CaSki + vehicle
      group and attenuated significantly by CUR (1,000 and 1,500 mg/kg). In conclusion,
      high dose CUR inhibited tumor growth and angiogenesis in CaSki-implanted mice
      probably mediated by the downregulation of VEGF, COX-2 and EGFR. CUR may have a
      role in treating human cervical cancer and should be explored further. 

PMID- 24860829
TI  - Microparticles: a new perspective in central nervous system disorders.
AB  - Microparticles (MPs) are a heterogeneous population of small cell-derived
      vesicles, ranging in size from 0.1 to 1  MU m. They contain a variety of
      bioactive molecules, including proteins, biolipids, and nucleic acids, which can
      be transferred between cells without direct cell-to-cell contact. Consequently,
      MPs represent a novel form of intercellular communication, which could play a
      role in both physiological and pathological processes. Growing evidence indicates
      that circulating MPs contribute to the development of cancer, inflammation, and
      autoimmune and cardiovascular diseases. Most cell types of the central nervous
      system (CNS) have also been shown to release MPs, which could be important for
      neurodevelopment, CNS maintenance, and pathologies. In disease, levels of certain
      MPs appear elevated; therefore, they may serve as biomarkers allowing for the
      development of new diagnostic tools for detecting the early stages of CNS
      pathologies. Quantification and characterization of MPs could also provide useful
      information for making decisions on treatment options and for monitoring success
      of therapies, particularly for such difficult-to-treat diseases as cerebral
      malaria, multiple sclerosis, and Alzheimer's disease. Overall, studies on MPs in
      the CNS represent a novel area of research, which promises to expand the
      knowledge on the mechanisms governing some of the physiological and
      pathophysiological processes of the CNS. 

PMID- 24860832
TI  - Cumulative effects of hypertension, dyslipidemia, and chronic kidney disease on
      carotid atherosclerosis in Chinese patients with type 2 diabetes mellitus.
AB  - AIMS. The aim of this study is to determine the extent of carotid atherosclerosis
      in Chinese patients with type 2 diabetes in relation to the cumulative
      atherosclerosis risk factors using ultrasonography. METHODS. The presence of
      hypertension, dyslipidemia, and chronic kidney disease (CKD) was documented in
      106 Chinese subjects with type 2 diabetes. Subjects with 0, 1, and >=2 additional
      atherosclerosis risk factors were assigned into groups 1, 2, and 3, respectively
      (n = 17, 49, and 40, resp.). Using ultrasound, the carotid arteries were assessed
      for the presence of carotid plaque, plaque score, intima-media thickness (IMT),
      and carotid arterial stiffness. RESULTS. With the adjustment for age and gender,
      the presence of plaque and plaque score were significantly higher in groups with
      more atherosclerosis risk factors (P < 0.05). In addition, age > 60 years old
      (odds ratio = 2.75; 95% CI: 1.26-6.0) and the presence of hypertension (odds
      ratio = 2.48; 95% CI: 1.11-5.58), dyslipidemia (odds ratio = 2.41; 95% CI: 1.05
      5.51), and CKD (odds ratio = 7.80; 95% CI: 1.46-41.72) could independently
      predict higher plaque score (P < 0.05). CONCLUSIONS. Hypertension, dyslipidemia,
      and CKD in Chinese patients with type 2 diabetes have cumulative effects on the
      burden of carotid plaque.

PMID- 24860831
TI  - How to take autophagy and endocytosis up a notch.
AB  - The interconnection of the endocytic and autophagosomal trafficking routes has
      been recognized more than two decades ago with both pathways using a set of
      identical effector proteins and sharing the same ultimate lysosomal destination.
      More recent data sheds light onto how other pathways are intertwined into this
      network, and how degradation via the endosomal/autophagosomal system may affect
      signaling pathways in multicellular organisms. Here, we briefly review the common
      features of autophagy and endocytosis and discuss how other players enter this
      mix with particular respect to the Notch signaling pathway. 

PMID- 24860833
TI  - Expression and clinical significance of YAP, TAZ, and AREG in hepatocellular
      carcinoma.
AB  - PURPOSE: Yes-associated protein (YAP) and PDZ-binding motif (TAZ) are two
      important effectors of Hippo pathway controlling the balance of organ size and
      carcinogenesis. Amphiregulin (AREG) is a member of the epidermal growth factor
      family, a direct target gene of YAP and TAZ. The role of these proteins in
      hepatocellular carcinoma (HCC) is unclear. METHODS: The expression of YAP, TAZ,
      and AREG in HCC was analyzed by immunohistochemical staining. The level of
      secreted serum AREG was also assayed by enzyme-linked immunosorbent (ELISA)
      assay. RESULTS: YAP, TAZ, and AREG were expressed in 69.2% (27/39), 66.7%
      (26/39), and 61.5% (24/39) of HCC patients. The expression of YAP was
      significantly correlated with Edmondson stage (P>0.05), serum AFP level (P>0.05),
      and HCC prognosis (P>0.05). AREG expression was also significantly correlated
      with Edmondson stage (P>0.05) and serum AFP level (P>0.05). In addition, the
      expression of serum AREG was higher than serum AFP in HCC patients. Further
      multivariate analysis showed that YAP expression was an independent prognostic
      factor that significantly affected the overall survival of HCC patients.
      CONCLUSIONS: YAP maybe an independent prognostic indicator for HCC patients and
      serum AREG may be a serological biomarker of HCC.

PMID- 24860835
TI  - Disruption of the suprachiasmatic nucleus blunts a time of day-dependent
      variation in systemic anaphylactic reaction in mice.
AB  - Anaphylaxis is a severe systemic allergic reaction which is rapid in onset and
      potentially fatal, caused by excessive release of mediators including histamine
      and cytokines/chemokines from mast cells and basophils upon allergen/IgE
      stimulation. Increased prevalence of anaphylaxis in industrialized countries
      requires urgent needs for better understanding of anaphylaxis. However, the
      pathophysiology of the disease is not fully understood. Here we report that the
      circadian clock may be an important regulator of anaphylaxis. In mammals, the
      central clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus
      synchronizes and entrains peripheral circadian clock present in virtually all
      cell types via neural and endocrine pathways, thereby driving the daily rhythms
      in behavior and physiology. We found that mechanical disruption of the SCN
      resulted in the absence of a time of day-dependent variation in passive systemic
      anaphylactic (PSA) reaction in mice, associated with loss of daily variations in
      serum histamine, MCP-1 (CCL2), and IL-6 levels. These results suggest that the
      central SCN clock controls the time of day-dependent variation in IgE-mediated
      systemic anaphylactic reaction, which may provide a novel insight into the
      pathophysiology of anaphylaxis. 

PMID- 24860834
TI  - Serum SALL4 is a novel prognosis biomarker with tumor recurrence and poor
      survival of patients in hepatocellular carcinoma.
AB  - AIM: Sal-like protein 4 (SALL4), is reexpressed in tissues of a subgroup of HCC
      associated with poor prognosis. Reports of SALL4 serological levels linked to HCC
      patients are meager and unclear in the prognosis of this malignancy. METHODS:
      Immunohistochemistry and optical microscopy protocols were used to examine the
      presence of SALL4 in liver tissues from the following patients: 38 HCC, 11
      chronic hepatitis B virus (HBV), 13 liver cirrhosis, and 12 healthy controls.
      Additionally, enzyme-linked immunosorbent assay (ELISA) was used to measure the
      SALL4 levels in serum samples isolated from patients as follows: 127 with HCC, 27
      with HBV, 24 with liver cirrhosis, and 23 normal controls. RESULTS: Analysis of
      liver tissues sections from HCC patients (18 out 38; 47.4%) showed positive
      staining for SALL4 and its expression did no correlate with any of the
      clinicopathologic characteristics. HCC patients displayed higher levels (50.4%)
      of SALL4 protein in serum, compared with the three control groups. Moreover,
      SALL4 concentration reached the maximum level after one week after treatment and
      dropped quickly after one month. These HCC patients showing high SALL4 serum
      levels had poor prognosis, evidenced by both tumor recurrence and overall
      survival rate. CONCLUSIONS: High SALL4 serum levels are a novel biomarker in the
      prognosis of HCC patients.

PMID- 24860836
TI  - Rheumatic fever associated with antiphospholipid syndrome: systematic review.
AB  - OBJECTIVE: To evaluate the clinical associations between rheumatic fever and
      antiphospholipid syndrome and the impact of coexistence of these two diseases in
      an individual. METHODS: Systematic review in electronics databases, regarding the
      period from 1983 to 2012. The keywords: "Rheumatic Fever," "Antiphospholipid
      Syndrome," and "Antiphospholipid Antibody Syndrome" are used. RESULTS: were
      identified 11 cases described in the literature about the association of
      rheumatic fever and antiphospholipid syndrome. Clinical presentation of rheumatic
      fever was characterized by the predominance of carditis (11/11) and chorea
      (7/11). Regarding the manifestations of APS, the stroke was observed in 7/11
      (63.6%), with one of them having probable embolic origin. CONCLUSION: The present
      study brings the information that the association between APS and RF is quite
      rare, however, is of great clinical importance. Doctors who deal with the RF
      should include in their differential diagnosis the APS, especially in the
      presence of stroke in patients with RF and whose echocardiogram does not show
      intracavitary thrombi.

PMID- 24860837
TI  - Antilymphocyte antibodies in systemic lupus erythematosus: association with
      disease activity and lymphopenia.
AB  - PURPOSE: We analyzed the prevalence, clinical correlation, and the functional
      significance of ALA in patients with systemic lupus erythematosus (SLE). METHODS:
      ALA IgG was detected by indirect immunofluorescence in the serum of 130 SLE
      patients, 75 patients with various rheumatic diseases, and 45 healthy controls
      (HC). RESULTS: The sensitivity and specificity of ALA IgG in SLE were 42.3% and
      96.7%, respectively. ALA was observed in 55.6% (50/90) of patients with
      lymphopenia, which was significantly higher than in patients with normal
      lymphocytes (5/40, 12.5%; P<0.001). Patients with active SLE showed higher ALA
      positivity (60.9%) than those with inactive disease (24.2%; chi2=17.925;
      P<0.001). ALA correlated significantly with hypocomplementemia, anti-dsDNA
      antibodies, and higher SLEDAI scores. The incidences of ALA in SLE patients who
      were seronegative for anti-dsDNA, anti-Sm, or both antibodies were 32.9% (26/79),
      41.0% (43/105), and 32.4% (22/68), respectively. The ALA-positive group also had
      higher incidences of neuropsychiatric SLE (NPSLE) and lupus nephritis (LN). In
      multivariate analyses, ALA was independently associated with lymphopenia, higher
      SLEDAI scores, and increased risk for LN. ALA titers significantly decreased as
      clinical disease was ameliorated following treatment. CONCLUSIONS: ALA occurred
      more frequently in patients with active SLE and was independently associated with
      lymphopenia, disease activity, and LN.

PMID- 24860839
TI  - Secondary Organic Aerosol Formation via 2-Methyl-3-buten-2-ol Photooxidation:
      Evidence of Acid-Catalyzed Reactive Uptake of Epoxides.
AB  - Secondary organic aerosol (SOA) formation from 2-methyl-3-buten-2-ol (MBO)
      photooxidation has recently been observed in both field and laboratory studies.
      Similar to the level of isoprene, the level of MBO-derived SOA increases with
      elevated aerosol acidity in the absence of nitric oxide; therefore, an epoxide
      intermediate, (3,3-dimethyloxiran-2-yl)methanol (MBO epoxide), was synthesized
      and tentatively proposed to explain this enhancement. In this study, the
      potential of the synthetic MBO epoxide to form SOA via reactive uptake was
      systematically examined. SOA was observed only in the presence of acidic aerosol.
      Major SOA constituents, 2,3-dihydroxyisopentanol and MBO-derived organosulfate
      isomers, were chemically characterized in both laboratory-generated SOA and in
      ambient fine aerosol collected from the BEACHON-RoMBAS field campaign during the
      summer of 2011, where MBO emissions are substantial. Our results support the idea
      that epoxides are potential products of MBO photooxidation leading to the
      formation of atmospheric SOA and suggest that reactive uptake of epoxides may
      explain acid enhancement of SOA observed from other biogenic hydrocarbons.

PMID- 24860838
TI  - Preferential autoimmune response in prostate cancer to cyclin B1 in a panel of
      tumor-associated antigens.
AB  - Previous studies have demonstrated that sera from patients with prostate cancer
      (PCa) contain autoantibodies that react with tumor-associated antigens (TAAs).
      Autoantibodies to cyclin B1 and fourteen other TAAs were detected by enzyme
      linked immunosorbent assay (ELISA) and Western blotting in 464 sera from patients
      with PCa, benign prostatic hyperplasia (BPH), and other controls. Autoantibodies
      to cyclin B1 were detected in 31.0% of sera from randomly selected patients with
      PCa versus 4.8% in sera with BPH. In the further analysis, 31.4% of sera from PCa
      patients at the early stage contained anti-cyclin B1 autoantibody, and even 29.4%
      of patients who had normal prostate-specific antigen (PSA) levels in their serum
      samples were observed anti-cyclin B1 positive. The cumulative positive rate of
      autoantibodies against seven selected TAAs (cyclin B1, survivin, p53,
      DFS70/LEDGFp75, RalA, MDM2, and NPM1) in PCa reached 80.5%, significantly higher
      than that in normal control sera. In summary, autoantibody to cyclin B1 might be
      a potential biomarker for the immunodiagnosis of early stage PCa, especially
      useful in patients with normal PSA level. This study further supports the
      hypothesis that a customized TAA array can be used for enhancing anti-TAA
      autoantibody detection, and it may constitute a promising and powerful tool for
      immunodiagnosis of PCa. 

PMID- 24860841
TI  - Widespread Exonization of Transposable Elements in Human Coding Sequences is
      Associated with Epigenetic Regulation of Transcription.
AB  - BACKGROUND: Transposable Elements (TEs) have long been regarded as selfish or
      junk DNA having little or no role in the regulation or functioning of the human
      genome. However, over the past several years this view came to be challenged as
      several studies provided anecdotal as well as global evidence for the
      contribution of TEs to the regulatory and coding needs of human genes. In this
      study, we explored the incorporation and epigenetic regulation of coding
      sequences donated by TEs using gene expression and other ancillary genomics data
      from two human hematopoietic cell-lines: GM12878 (a lymphoblastoid cell line) and
      K562 (a Chronic Myelogenous Leukemia cell line). In each cell line, we found
      several thousand instances of TEs donating coding sequences to human genes. We
      compared the transcriptome assembly of the RNA sequencing (RNA-Seq) reads with
      and without the aid of a reference transcriptome and found that the percentage of
      genes that incorporate TEs in their coding sequences is significantly greater
      than that obtained from the reference transcriptome assemblies using Refseq and
      Gencode gene models. We also used histone modifications chromatin
      immunoprecipitation sequencing (ChIP-Seq) data, Cap Analysis of Gene Expression
      (CAGE) data and DNAseI Hypersensitivity Site (DHS) data to demonstrate the
      epigenetic regulation of the TE derived coding sequences. Our results suggest
      that TEs form a significantly higher percentage of coding sequences than
      represented in gene annotation databases and these TE derived sequences are
      epigenetically regulated in accordance with their expression in the two cell
      types.

PMID- 24860840
TI  - Preoperative cerebrospinal fluid beta-Amyloid/Tau ratio and postoperative
      delirium.
AB  - OBJECTIVE: The neuropathogenesis of postoperative delirium remains unknown. Low
      cerebrospinal fluid (CSF) betaamyloid protein (Abeta) and high CSF Tau levels are
      associated with Alzheimer's disease. We therefore assessed whether lower
      preoperative CSF Abeta/Tau ratio was associated with higher incidence and greater
      severity of postoperative delirium. METHODS: One hundred and fifty three
      participants (71+/-5 years, 53% males) who had total hip/knee replacement under
      spinal anesthesia were enrolled. CSF was obtained during initiation of spinal
      anesthesia. The incidence and severity of postoperative delirium were determined
      by Confusion Assessment Method (CAM) and Memorial Delirium Assessment Scale
      (MDAS) on postoperative day 1 and 2. Abeta40, Abeta42, and Tau levels in the CSF
      were measured by enzyme-linked immunosorbent assay. The relationships among these
      variables were determined, adjusting for age and gender. RESULTS: Participants in
      the lowest quartile of preoperative CSF Abeta40/Tau and Abeta42/Tau ratio had
      higher incidence (32% versus 17%, P=0. 0482) and greater symptom severity of
      postoperative delirium (Abeta40/Tau ratio: 4 versus 3, P=0. 034; Abeta42/Tau
      ratio: 4 versus 3, P=0. 062, the median of the highest Memorial Delirium
      Assessment Scale score) as compared to the combination of the rest of the
      quartiles. The preoperative CSF Abeta40/Tau or Abeta42/Tau ratio was inversely
      associated with Memorial Delirium Assessment Scale score (Abeta40/Tau ratio: 
      0.12+/-0.05, P=0.014, adj. -0.12+/-0.05, P=0.018; Abeta42/Tau ratio: -0.65+/
      0.26, P=0.013, adj. -0.62+/-0.27, P=0.022). INTERPRETATION: Lower CSF Abeta/Tau
      ratio could be associated with postoperative delirium, pending confirmation of
      our preliminary results in further studies. These findings suggest potential
      roles of Abeta and/or Tau in postoperative delirium neuropathogenesis.

PMID- 24860842
TI  - Gene Deletion of VIP Leads to Increased Mortality Associated with Progressive
      Right Ventricular Hypertrophy.
AB  - Vasoactive Intestinal Peptide (VIP) knockout mice exhibit asthma, pulmonary
      hypertension, and left ventricular wall thinning. Humans with these disorders
      have premature death. We show here that VIP KO mice have reduced survival (100%
      mortality at 20 months), vs. 100% survival among WT C57BL/6 mice. Moreover, the
      ratios of weights of right ventricle divided by left ventricle plus septum were
      progressively increased in VIP KO mice with age. Core temperatures were lower in
      VIP KO mice when compared to WT littermates, with an associated pro-inflammatory
      cytokine milieu. Overall, our results indicate that VIP is important for survival
      in mice. Its absence leads to increased mortality, with progressive right
      ventricular hypertrophy as a surrogate of pulmonary hypertension, lower body
      weight, hypothermia, and pro-inflammatory milieu. These studies support VIP as a
      novel therapeutic agent in pulmonary hypertension.

PMID- 24860843
TI  - Synthesis, crystal structure and photocatalytic properties of an unprecedented
      arsenic-disubstituted Lindqvist-type peroxopolyoxoniobate ion:
      {As2Nb4(O2)4O14H1.5}(4.5-).
AB  - An unprecedented arsenic-disubstituted Lindqvist-type peroxopolyoxoniobate
      Cs2.5Na2{As2Nb4(O2)4O14H1.5}.11H2O has been successfully synthesized and
      characterized. The photocatalytic activity of the cluster for H2 evolution from
      water is investigated by irradiating with a 300 W Xe lamp, which shows a certain
      photocatalytic water splitting activity. 

PMID- 24860844
TI  - TOF-SIMS characterization of impurity enrichment and redistribution in solid
      oxide electrolysis cells during operation.
AB  - TOF-SIMS analyses of state-of-the-art high temperature solid oxide electrolysis
      cells before and after testing under different operating conditions were
      performed. The investigated cells consist of an yttria stabilized zirconia (YSZ)
      electrolyte, a La1-xSrxMnO3-delta composite anode and a Ni-YSZ cermet cathode.
      The surfaces and cross-sections of the cells were analyzed, and several elemental
      impurities like Si, Ca and Na were identified and spatially mapped and their
      enrichment and migration during operation is reported. With advancing operation
      time, the concentration of these elements, especially Na and Ca, increases. For
      Si, a concentration gradient is found from the gas inlet to the gas outlet.
      Additionally, a loss of Ni percolation in the active cathode is observed in the
      same area where the Si enrichment is found. Based on the obtained TOF-SIMS
      results, the influence of the operating conditions on degradation is discussed. 

PMID- 24860846
TI  - Simultaneous thermal and optical imaging of two-phase flow in a micro-model.
AB  - In the study of non-equilibrium heat transfer in multiphase flow in porous media,
      parameters and constitutive relations, like heat transfer coefficients between
      phases, are unknown. In order to study the temperature development of a
      relatively hot invading immiscible non-wetting fluid and, ultimately, approximate
      heat transfer coefficients, a transparent micro-model is used as an artificial
      porous medium. In the last few decades, micro-models have become popular
      experimental tools for two-phase flow studies. In this work, the design of an
      innovative, elongated, PDMS (polydimethylsiloxane) micro-model with dimensions of
      14.4 * 39 mm(2) and a constant depth of 100 microns is described. A novel setup
      for simultaneous thermal and optical imaging of flow through the micro-model is
      presented. This is the first time that a closed flow cell like a micro-model is
      used in simultaneous thermal and optical flow imaging. The micro-model is
      visualized by a novel setup that allowed us to monitor and record the
      distribution of fluids throughout the length of the micro-model continuously and
      also record the thermal signature of the fluids. Dynamic drainage and imbibition
      experiments were conducted in order to obtain information about the heat exchange
      between the phases. In this paper the setup as well as analysis and qualitative
      results are presented. 

PMID- 24860845
TI  - Hydrogel bioprinted microchannel networks for vascularization of tissue
      engineering constructs.
AB  - Vascularization remains a critical challenge in tissue engineering. The
      development of vascular networks within densely populated and metabolically
      functional tissues facilitate transport of nutrients and removal of waste
      products, thus preserving cellular viability over a long period of time. Despite
      tremendous progress in fabricating complex tissue constructs in the past few
      years, approaches for controlled vascularization within hydrogel based engineered
      tissue constructs have remained limited. Here, we report a three dimensional (3D)
      micromolding technique utilizing bioprinted agarose template fibers to fabricate
      microchannel networks with various architectural features within
      photocrosslinkable hydrogel constructs. Using the proposed approach, we were able
      to successfully embed functional and perfusable microchannels inside
      methacrylated gelatin (GelMA), star poly(ethylene glycol-co-lactide) acrylate
      (SPELA), poly(ethylene glycol) dimethacrylate (PEGDMA) and poly(ethylene glycol)
      diacrylate (PEGDA) hydrogels at different concentrations. In particular, GelMA
      hydrogels were used as a model to demonstrate the functionality of the fabricated
      vascular networks in improving mass transport, cellular viability and
      differentiation within the cell-laden tissue constructs. In addition, successful
      formation of endothelial monolayers within the fabricated channels was confirmed.
      Overall, our proposed strategy represents an effective technique for
      vascularization of hydrogel constructs with useful applications in tissue
      engineering and organs on a chip. 

PMID- 24860847
TI  - Functionalization of protein-based nanocages for drug delivery applications.
AB  - Traditional drug delivery strategies involve drugs which are not targeted towards
      the desired tissue. This can lead to undesired side effects, as normal cells are
      affected by the drugs as well. Therefore, new systems are now being developed
      which combine targeting functionalities with encapsulation of drug cargo. Protein
      nanocages are highly promising drug delivery platforms due to their perfectly
      defined structures, biocompatibility, biodegradability and low toxicity. A
      variety of protein nanocages have been modified and functionalized for these
      types of applications. In this review, we aim to give an overview of different
      types of modifications of protein-based nanocontainers for drug delivery
      applications. 

PMID- 24860848
TI  - Syntheses of quinazolinones from 2-iodobenzamides and enaminones via copper
      catalyzed domino reactions.
AB  - N-Substituted 2-iodobenzamides and enaminones undergo cascade transformations to
      achieve quinazolinones via a copper-catalyzed Ullmann-type coupling, a Michael
      addition and a retro-Mannich reaction. A unique stereochemical feature of this
      domino process was that Z-enaminones reacted without external ligands, whereas E
      enaminones required the assistance of ligands. 

PMID- 24860849
TI  - Ellipsoidal particles encapsulated in droplets.
AB  - Using hydrodynamic focusing, we encapsulated polystyrene ellipsoidal particles in
      water droplets dispersed in an immiscible, continuous phase of light mineral oil.
      The axisymmetric shape of the drop partially encapsulating an elongated particle
      was computed as a function of the particle aspect ratio, droplet volume, and
      contact angle. When the droplet volume is within a certain range, pinned
      (partially engulfed) and fully engulfed equilibrium configurations coexist.
      Partial encapsulation may be preferred (has a lower free energy) even when the
      droplet's volume is sufficient to fully engulf the particle. The co-existence of
      multiple equilibrium states suggests possible hysteretic encapsulation behavior.
      We also estimate the axial capillary force exerted by the droplet on the particle
      as a function of volume and contact angle. The theoretical predictions are
      critically compared with experimental observations. 

PMID- 24860851
TI  - Common challenge topics in pediatric transplantation.
AB  - This special issue is dedicated to the common challenge topics in pediatric
      transplantation. It contains 11 chapters, ranging from clinical research in
      pediatric transplantation to translational research (from bench to bedside). It
      includes comprehensive reviews from renowned scientists, clinicians and surgeons
      from five countries from the International Pediatric Transplantation Association
      (IPTA), Harvard University, the University of Miami and the University of Sao
      Paulo Medical School. The clinical management of specific issues, such as
      sensitized patients and ABO blood type-incompatible transplantation, is
      addressed. In addition, the challenges facing this patient population and the
      future perspectives for clinical research are discussed. 

PMID- 24860850
TI  - Self-assembly of an azobenzene-containing polymer prepared by a multi-component
      reaction: supramolecular nanospheres with photo-induced deformation properties.
AB  - In this article, we have synthesized a polymer containing regulated azobenzene
      groups by one-pot multi-component polymerization (MCP) based on Passerini
      reaction, and investigated its self-assembly behavior and photo-induced
      deformation properties. We found that this molecule can form spherical structures
      with sizes ranging from hundreds of nanometers to several micrometers when
      dissolved in THF. NMR and FTIR studies indicate that there are associated
      hydrogen bonds among the molecules in the aggregates, which are responsible for
      the formation of the nanospheres. By controlling the stirring rate as the THF
      suspension is dropped into water, the nanospheres can be sorted according to
      their size. In this way, we have obtained nanospheres with relatively uniform
      diameter. When irradiated by UV light in the aqueous medium, the nanospheres tend
      to aggregate into large clusters, while in dry state they are ready to merge into
      island-like structures, showing a good photo-induced deformation property. 

PMID- 24860852
TI  - Growth following solid organ transplantation in childhood.
AB  - One of the ultimate goals of successful solid organ transplantation in pediatric
      recipients is attaining an optimal final adult height. This manuscript will
      discuss growth following transplantation in pediatric recipients of kidney,
      liver, heart, lung or small bowel transplants. Remarkably similar factors impact
      growth in all of these recipients. Age is a primary factor, with younger
      recipients exhibiting the greatest immediate catch-up growth. Graft function is a
      significant contributing factor, with a reduced glomerular filtration rate
      correlating with poor growth in kidney recipients and the need for re
      transplantation with impaired growth in liver recipients. The known adverse
      impact of steroids on growth has led to modification of the steroid dose and even
      steroid withdrawal and avoidance. In kidney and liver recipients, this strategy
      has been associated with the development of acute rejection. In infant heart
      transplantation, avoiding maintenance corticosteroid immunosuppression is
      associated with normal growth velocity in the majority of patients. With marked
      improvements in patient and graft survival rates in pediatric organ recipients,
      quality of life issues, such as normal adult height, should now receive paramount
      attention. In general, normal growth following solid organ transplantation should
      be an achievable goal that results in normal adult height. 

PMID- 24860853
TI  - New immunosuppressive agents in pediatric transplantation.
AB  - Immunosuppressive therapy in pediatrics continues to evolve. Over the past
      decade, newer immunosuppressive agents have been introduced into adult and
      pediatric transplant patients with the goal of improving patient and allograft
      survival. Unfortunately, large-scale randomized clinical trials are not commonly
      performed in children. The purpose of this review is to discuss the newer
      immunosuppressive agents available for induction therapy, maintenance
      immunosuppression, and the treatment of rejection. 

PMID- 24860854
TI  - Challenges with sensitized recipients in pediatric heart transplantation.
AB  - The sensitization of patients to human leukocyte antigens prior to heart
      transplantation is increasingly being recognized as an important challenge both
      before and after the transplant, and the effects of sensitization on clinical
      outcomes are just beginning to be understood. Many patients are listed with the
      requirement of a negative prospective or virtual crossmatch prior to accepting a
      donor organ. This strategy has been associated with both longer waitlist times
      and higher waitlist mortality. An alternative approach is to transplant across a
      potentially positive crossmatch while utilizing strategies to decrease the
      significance of the human leukocyte antigen antibodies. This review will examine
      the challenges and the impact of sensitization on pediatric patients prior to and
      following heart transplantation. 

PMID- 24860855
TI  - ABO-incompatible living-donor pediatric kidney transplantation in Japan.
AB  - The Japanese ABO-Incompatible Transplantation Committee officially collected and
      analyzed data on pediatric ABO-incompatible living-donor kidney transplantation
      in July 2012. The age of a child was defined as <16 years, and 89 children who
      had undergone ABO-incompatible living-donor kidney transplantation from 1989 to
      2011 were entered in a registry. These data were presented as the Japanese
      registry of pediatric ABO-incompatible living-donor kidney transplantation at the
      regional meetings of the International Pediatric Transplantation Association
      (IPTA) in Nagoya in September 2012 and in Sao Paulo in November 2012. 

PMID- 24860857
TI  - Current management issues of immediate postoperative care in pediatric kidney
      transplantation.
AB  - The number of pediatric kidney transplants has been increasing in many centers
      worldwide, as the procedure provides long-lasting and favorable outcomes;
      however, few papers have addressed the immediate postoperative care of this
      unique population. Herein, we describe the management of these patients in the
      early postoperative phase. After the surgical procedure, children should ideally
      be managed in a pediatric intensive care unit, and special attention should be
      given to fluid balance, electrolyte disturbances and blood pressure control.
      Antibiotic and antiviral prophylaxes are usually performed and are based on the
      recipient and donor characteristics. Thrombotic prophylaxis is recommended for
      children at high risk for thrombosis, although consensus on the optimum therapy
      is lacking. Image exams are essential for good graft control, and Doppler
      ultrasound must be routinely performed on the first operative day and promptly
      repeated if there is any suspicion of kidney dysfunction. Abdominal drains can be
      helpful for surveillance in patients with increased risk of surgical
      complications, such as urinary fistula or bleeding, but are not routinely
      required. The immunosuppressive regimen starts before or at the time of kidney
      transplantation and is usually based on induction with monoclonal or polyclonal
      antibodies, depending on the immunological risk, and maintenance with a
      calcineurin inhibitor (tacrolimus or ciclosporin), an anti-proliferative agent
      (mycophenolate or azathioprine) and steroids. 

PMID- 24860858
TI  - Postoperative care in pediatric liver transplantation.
AB  - In the last 25 years, liver transplantation in children has become an effective,
      definitive, and universally accepted treatment for terminal liver diseases. Long
      term survival exceeds 80% and improves each year as the result of constant
      technical advancements and improvements in immediate postoperative intensive care
      and clinical control. 

PMID- 24860859
TI  - Clinical recommendations for postoperative care after heart transplantation in
      children: 21 years of a single-center experience.
AB  - Heart transplantation is an option for children with complex congenital heart
      disease and cardiomyopathies. A patient's quality of life and long-term survival
      depend on successful management of the surgical complications and adverse side
      effects of immunosuppression. The purpose of this review was to summarize the
      practical management of postoperative care in this patient population and to make
      recommendations for the future. 

PMID- 24860856
TI  - Long-term outcomes of children after solid organ transplantation.
AB  - Solid organ transplantation has transformed the lives of many children and adults
      by providing treatment for patients with organ failure who would have otherwise
      succumbed to their disease. The first successful transplant in 1954 was a kidney
      transplant between identical twins, which circumvented the problem of rejection
      from MHC incompatibility. Further progress in solid organ transplantation was
      enabled by the discovery of immunosuppressive agents such as corticosteroids and
      azathioprine in the 1950s and ciclosporin in 1970. Today, solid organ
      transplantation is a conventional treatment with improved patient and allograft
      survival rates. However, the challenge that lies ahead is to extend allograft
      survival time while simultaneously reducing the side effects of
      immunosuppression. This is particularly important for children who have
      irreversible organ failure and may require multiple transplants. Pediatric
      transplant teams also need to improve patient quality of life at a time of
      physical, emotional and psychosocial development. This review will elaborate on
      the long-term outcomes of children after kidney, liver, heart, lung and
      intestinal transplantation. As mortality rates after transplantation have
      declined, there has emerged an increased focus on reducing longer-term morbidity
      with improved outcomes in optimizing cardiovascular risk, renal impairment,
      growth and quality of life. Data were obtained from a review of the literature
      and particularly from national registries and databases such as the North
      American Pediatric Renal Trials and Collaborative Studies for the kidney, SPLIT
      for liver, International Society for Heart and Lung Transplantation and UNOS for
      intestinal transplantation. 

PMID- 24860860
TI  - Pediatric lung transplantation: 10 years of experience.
AB  - Lung transplantation is a well-established treatment for advanced lung diseases.
      In children, the diseases that most commonly lead to the need for a
      transplantation are cystic fibrosis, pulmonary hypertension, and bronchiolitis.
      However, the number of pediatric lung transplantations being performed is low
      compared with the number of transplants performed in the adult age group. The
      objective of this study was to demonstrate our experience with pediatric lung
      transplants over a 10-year period in a program initially designed for adults. 

PMID- 24860862
TI  - Clinical research in pediatric organ transplantation.
AB  - Solid organ transplantation has greatly improved survival in children with end
      stage disease, becoming one of the main treatment options in this population.
      Nonetheless, there are significant challenges associated with validating and
      optimizing the effects of these interventions in clinical trials. Therefore, we
      reviewed the main issues related to conducting clinical transplantation research
      in children. We divided these challenges into three different categories: (i)
      challenges related to surgical techniques and anesthetic procedures, (ii)
      challenges related to post-transplant care and (iii) challenges specific to a
      particular population group and disease type. Some of the observed burdens for
      clinical research in this field are related to the limitations of conducting
      studies with a placebo or sham procedure, determining the standard of care for a
      control group, low prevalence of cases, ethical concerns related to use of a
      placebo control group and lack of generalizability from animal studies and
      clinical trials conducted in adult populations. To overcome some of these
      barriers, it is necessary to utilize alternative clinical trial designs, such as
      observational studies or non-inferiority trials, and to develop multicenter
      collaborations to increase the recruitment rate. In conclusion, the lack of
      robust data related to pediatric transplantation remains problematic, and further
      clinical trials are needed to develop more efficacious and safer treatments. 

PMID- 24860863
TI  - Drugs for macular degeneration, price discrimination, and Medicare's
      responsibility not to overpay.

PMID- 24860864
TI  - A multilevel hierarchical finite element model for capillary failure in soft
      tissue.
AB  - Bruising, the result of capillary failure due to trauma, is a common indication
      of abuse. However, the etiology of capillary failure has yet to be determined as
      the scale change from tissue to capillary represents several orders of magnitude.
      As a first step toward determining bruise etiology, we have developed a
      multilevel hierarchical finite element model (FEM) of a portion of the upper
      human arm using a commercial finite element tool and a series of three
      interconnected hierarchical submodels. The third and final submodel contains a
      portion of the muscle tissue in which a single capillary is embedded. Nonlinear,
      hyperelastic material properties were applied to skin, adipose, muscle, and
      capillary wall materials. A pseudostrain energy method was implemented to
      subtract rigid-body-like motion of the submodel volume experienced in the global
      model, and was critical for convergence and successful analyses in the submodels.
      The deformation and hoop stresses in the capillary wall were determined and
      compared with published capillary failure stress. For the dynamic load applied to
      the skin of the arm (physiologically simulating a punch), the model predicted
      that approximately 8% volume fraction of the capillary wall was above the
      reference capillary failure stress, indicating bruising would likely occur.

PMID- 24860865
TI  - Bioengineered stromal cell-derived factor-1alpha analogue delivered as an
      angiogenic therapy significantly restores viscoelastic material properties of
      infarcted cardiac muscle.
AB  - Ischemic heart disease is a major health problem worldwide, and current therapies
      fail to address microrevascularization. Previously, our group demonstrated that
      the sustained release of novel engineered stromal cell-derived factor 1-a
      analogue (ESA) limits infarct spreading, collagen deposition, improves cardiac
      function by promoting angiogenesis in the region surrounding the infarct, and
      restores the tensile properties of infarcted myocardium. In this study, using a
      well-established rat model of ischemic cardiomyopathy, we describe a novel and
      innovative method for analyzing the viscoelastic properties of infarcted
      myocardium. Our results demonstrate that, compared with a saline control group,
      animals treated with ESA have significantly improved myocardial relaxation rates,
      while reducing the transition strain, leading to restoration of left ventricular
      mechanics.

PMID- 24860861
TI  - Issues in solid-organ transplantation in children: translational research from
      bench to bedside.
AB  - In this review, we identify important challenges facing physicians responsible
      for renal and cardiac transplantation in children based on a review of the
      contemporary medical literature. Regarding pediatric renal transplantation, we
      discuss the challenge of antibody-mediated rejection, focusing on both acute and
      chronic antibody-mediated rejection. We review new diagnostic approaches to
      antibody-mediated rejection, such as panel-reactive antibodies, donor-specific
      cross-matching, antibody assays, risk assessment and diagnosis of antibody
      mediated rejection, the pathology of antibody-mediated rejection, the issue of
      ABO incompatibility in renal transplantation, new therapies for antibody-mediated
      rejection, inhibiting of residual antibodies, the suppression or depletion of B
      cells, genetic approaches to treating acute antibody-mediated rejection, and
      identifying future translational research directions in kidney transplantation in
      children. Regarding pediatric cardiac transplantation, we discuss the mechanisms
      of cardiac transplant rejection, including the role of endomyocardial biopsy in
      detecting graft rejection and the role of biomarkers in detecting cardiac graft
      rejection, including biomarkers of inflammation, cardiomyocyte injury, or stress.
      We review cardiac allograft vasculopathy. We also address the role of genetic
      analyses, including genome-wide association studies, gene expression profiling
      using entities such as AlloMap(r), and adenosine triphosphate release as a
      measure of immune function using the Cylex(r) ImmuKnowTM cell function assay.
      Finally, we identify future translational research directions in heart
      transplantation in children. 

PMID- 24860867
TI  - Impact of pharmacist integration in a pediatric primary care clinic on
      vaccination errors: a retrospective review.
AB  - OBJECTIVE: To measure the impact of ambulatory clinical pharmacist integration in
      a pediatric primary care clinic on vaccination error rates and to evaluate missed
      opportunities. METHODS: A retrospective, quasi-experimental review of electronic
      medical records of visit encounters during a 3-month period compared vaccine
      error rates and missed opportunities between two pediatric residency primary care
      clinics. The intervention clinic has a full-time ambulatory clinical pharmacist
      integrated into the health care team. Pharmacy services were not provided at the
      comparison clinic. A vaccine error was defined as follows: doses administered
      before minimum recommended age, doses administered before minimum recommended
      spacing from a previous dose, doses administered unnecessarily, live virus
      vaccination administered too close to a previous live vaccine, and doses invalid
      for combinations of these reasons. RESULTS: 900 encounters were randomly selected
      and reviewed. The error rate was found to be 0.28% in the intervention clinic and
      2.7% in the comparison clinic. The difference in error rates was found to be
      significant (P = 0.0021). The number of encounters with greater than or equal to
      one missed opportunity was significantly higher in the comparison clinic compared
      with the intervention clinic (29.3% vs. 10.2%; P <0.0001). CONCLUSION: The
      pediatric primary care clinic with a pharmacist had reductions in vaccination
      errors as well as missed opportunities. Pharmacists play a key role in the
      pediatric primary care team to improve the appropriate use of vaccines.

PMID- 24860868
TI  - Concise review: MicroRNA function in multipotent mesenchymal stromal cells.
AB  - Multipotent mesenchymal stromal cells (MSCs) are ideal candidates for different
      cellular therapies due to their simple isolation, extensive expansion potential,
      and low immunogenicity. For various therapeutic approaches, such as bone and
      cartilage repair, MSCs are expected to contribute by direct differentiation to
      replace the damaged tissue, while many other applications rely on the secretion
      of paracrine factors which modulate the immune response and promote angiogenesis.
      MicroRNAs (miRNAs), which target messenger RNA for cleavage or translational
      repression, have recently been shown to play critical functions in MSC to
      regulate differentiation, paracrine activity, and other cellular properties such
      as proliferation, survival, and migration. The global miRNA expression profile of
      MSC varies according to the tissue of origin, species, and detection methodology,
      while also certain miRNAs are consistently found in all types of MSC. The
      function in MSC of more than 60 different miRNAs has been recently described,
      which is the subject of this review. A special emphasis is given to miRNAs that
      have demonstrated a function in MSC in vivo. We also present in detail miRNAs
      with overlapping effects (i.e., common target genes) and discuss future
      directions to deepen our understanding of miRNA biology in MSC. These recent
      discoveries have opened the possibility of modulating miRNAs in MSC, in order to
      enhance their proregenerative, therapeutic potential.

PMID- 24860866
TI  - Prescription medication burden in patients with newly diagnosed diabetes: a
      SUrveillance, PREvention, and ManagEment of Diabetes Mellitus (SUPREME-DM) study.
AB  - OBJECTIVE: To understand the burden of medication use for patients with newly
      diagnosed diabetes both before and after diabetes diagnosis and to identify
      subpopulations of patients with newly diagnosed diabetes who face a relatively
      high drug burden. DESIGN: Retrospective cohort study. SETTING: 11 integrated
      health systems in the United States. PARTICIPANTS: 196,654 insured adults 20
      years of age or older newly diagnosed with type 1 or type 2 diabetes from January
      2005 through December 2009. MAIN OUTCOME MEASURES: Number of unique therapeutic
      classes of drugs dispensed in the 12 months before and 12 months after diagnosis
      of diabetes in five categories: overall, antihypertensive agents,
      antihyperlipidemic agents, mental health agents, and antihyperglycemic agents (in
      the postdiagnosis period only). RESULTS: The mean number of drug classes used by
      newly diagnosed patients with diabetes is high before diagnosis (5.0) and
      increases significantly afterward (6.6). Of this increase, 81% is due to
      antihyperglycemic initiation and increased use of medications to control
      hypertension and lipid levels. Multivariate analyses showed that overall drug
      burden after diabetes diagnosis was higher in women, older, white, and obese
      patients, as well as among those with higher glycosylated hemoglobin
      concentrations and comorbidity levels (significant for all comparisons). The
      overall number of drug classes used by newly diagnosed patients with diabetes
      after diagnosis decreased slightly but significantly between 2005 and 2009.
      CONCLUSION: Patients newly diagnosed with diabetes face a substantially increased
      burden of medications used to control diabetes and other comorbidities. This
      study shows an increased focus on cardiovascular disease risk factor control
      after diagnosis of diabetes. However, total drug burden may be slightly
      decreasing over time.

PMID- 24860869
TI  - Formation of adherens and communicating junctions coordinate the differentiation
      of the shedding-layer and beta-epidermal generation in regenerating lizard
      epidermis.
AB  - In the lizard epidermis, the formation of a stratified alpha- and beta-layer,
      separated by a shedding complex for molting, suggests that keratinocytes
      communicate in a coordinated manner after they leave the basal layers during the
      shedding cycle. I have therefore studied the localization of cell junctional
      proteins such as beta-catenin and connexins 43 and 26 during scale regeneration
      in lizard using immunocytochemistry. Beta-catenin is also detected in nuclei of
      basal cells destined to give rise to the Oberhautchen and beta-cells suggesting
      activation of the Wnt-pathway during beta-cell differentiation. The observations
      show that cells of the entire shedding layer (clear and Oberhautchen) and beta
      layer are connected by beta-catenin (adherens junctions) and connexins
      (communicating junctions) during their differentiation. This likely cell coupling
      determines the formation of a distinct shedding and beta-layer within the
      regenerating epidermis. The observed pattern of cell junctional stratification
      suggests that after departing from the basal layer Oberhautchen and beta-cells
      form a continuous communicating compartment that coordinates the contemporaneous
      differentiation along the entire scale. While the beta-layer matures the
      junctions are lost while other cell junctions are formed in the following mesos-
      and alpha-cell layers. This process determines the formation of layers with
      different texture (harder or softer) and the precise localization of the shedding
      layer within lizard epidermis.

PMID- 24860870
TI  - Bevacizumab for newly diagnosed glioblastoma.

PMID- 24860872
TI  - Analysis of 5-lipoxygenase phosphorylation on molecular level by MALDI-MS.
AB  - The enzyme 5-lipoxygenase (5-LO) catalyzes the first reactions in the
      biosynthesis of leukotrienes, powerful lipid mediators that are involved in
      several physiological and pathological processes. 5-LO activity is tightly
      regulated by several factors, including post translational modifications (PTMs).
      Phosphorylations of 5-LO by the kinases extracellular signal-regulated kinase 2
      (Erk2), mitogen-activated protein kinase activated protein kinase 2 (MK2) and
      protein kinase A (PKA) have been described to regulate 5-LO activity.
      Furthermore, 5-LO phosphorylation is considered a determinant of drug candidate
      potency. However, no evidence on a molecular level, as can be provided by MS, has
      as yet been presented for these PTMs. Here, we employ a workflow including
      different proteolytic cleavages and phosphopeptide enrichment for detection of 5
      LO phosphorylation by MALDI-MS. Proof for the known phosphorylation sites of MK2
      (Ser271) and PKA (Ser523) was provided by MS after in vitro phosphorylation, but
      not for the postulated Erk2 site (Ser663). Detection limits have been determined
      for all three sites. Moreover, we identified novel tyrosine kinase target sites
      within 5-LO using in silico and in vitro methods. Tyr42, Tyr53 and either Tyr94
      or Tyr445 were phosphorylated by the Src kinases Fgr, hematopoietic cell kinase
      (HCK) and Yes. To analyze the phosphorylation state in the cellular context, we
      created stably 5-LO-transduced Mono Mac 6 cells. Here, we only detected phospho
      Ser271 by MS, whereas immunoblot analysis indicated tyrosine phosphorylation,
      phospho-Ser271 and phospho-Ser663. Unexpectedly, phospho-Ser271 occurred
      independent of cell stimulation. Taken together, we describe a method for the
      molecular analysis of 5-LO phosphorylation, provide insights regarding the
      occurrence of known phosphorylation sites partly in contrast to earlier studies
      and present first evidence on novel phosphosites.

PMID- 24860871
TI  - Erythropoiesis-driven regulation of hepcidin in human red  cell disorders is
      better reflected through concentrations of  soluble transferrin receptor rather
      than growth  differentiation factor 15.
AB  - Growth differentiation factor 15 (GDF-15) is a bone marrow-derived cytokine whose
      ability to suppress iron regulator hepcidin in vitro and increased concentrations
      found in patients with ineffective erythropoiesis (IE)suggest that hepcidin
      deficiency mediated by GDF-15 may be the pathophysiological explanation for
      nontransfusional iron overload. We aimed to compare GDF-15 production in anemic
      states with different types of erythropoietic dysfunction. Complete blood counts,
      biochemical markers of iron status, plasma hepcidin, GDF-15, and known hepcidin
      regulators [interleukin-6 and erythropoietin (EPO)] were measured in 87 patients
      with red cell disorders comprising IE and hemolytic states: thalassemia, sickle
      cell anemia, and cobalamin deficiency. Healthy volunteers were also evaluated for
      comparison. Neither overall increased EPO,nor variable GDF-15 concentrations
      correlated with circulating hepcidin concentrations (P = 0.265 and P = 0.872).
      Relative hepcidin deficiency was found in disorders presenting with concurrent
      elevation of GDF-15 and soluble transferrin receptor (sTfR), a biomarker of
      erythropoiesis, and sTfR had the strongest correlation with hepcidin (r(s) =
      0.584, P < 0.0001). Our data show that high concentrations of GDF-15 in vivo are
      not necessarily associated with pathological hepcidin reduction, and hepcidin
      deficiency was only found when associated with sTfR overproduction. sTfR
      elevation may be a necessary common denominator of erythropoiesis-driven
      mechanisms to favor iron absorption in anemic states and appears a suitable
      target for investigative approaches to iron disorders.

PMID- 24860873
TI  - Weak protein complexes: challenging to study but essential for life.

PMID- 24860874
TI  - Bifunctional ADP-dependent phosphofructokinase/glucokinase activity in the order
      Methanococcales--biochemical characterization of the mesophilic enzyme from
      Methanococcus maripaludis.
AB  - In some archaea, the phosphorylation of glucose and fructose 6-phosphate
      (fructose 6P) is carried out by enzymes that are specific for either substrate
      and that use ADP as phosphoryl donor. In the hyperthermophilic archaeon
      Methanocaldococcus jannaschii, a bifunctional enzyme able to phosphorylate
      glucose and fructose 6P has been described. To determine whether the ability to
      phosphorylate both glucose and fructose 6P is a common feature for all enzymes of
      the order Methanococcales, we expressed, purified and characterized the unique
      homologous protein of the mesophilic archaea Methanococcus maripaludis. Assay of
      the enzyme activity with different sugars, metals and nucleotides allows us to
      conclude that the enzyme is able to phosphorylate both fructose 6P and glucose in
      the presence of ADP and a divalent metal cation. Kinetic characterization of the
      enzyme revealed complex regulation by the free Mg(2+) concentration and AMP, with
      the latter appearing to be a key metabolite. To determine whether this enzyme
      could have a role in gluconeogenesis, we evaluated the reversibility of both
      reactions and found that glucokinase activity is reversible, whereas
      phosphofructokinase activity is not. To determine the important residues for
      glucose and fructose 6P binding, we modeled the bifunctional
      phosphofructokinase/glucokinase enzyme from M. maripaludis and its interactions
      with both sugar substrates using protein-ligand docking. Comparison of the active
      site of the phosphofructokinase/glucokinase enzyme from M. maripaludis with the
      structural models constructed for all the homology sequences present in the order
      Methanococcales shows that all of the ADP-dependent kinases from this order would
      be able to phosphorylate glucose and fructose 6P, which rules out the current
      annotation of these enzymes as specific phosphofructokinases.

PMID- 24860876
TI  - Technology: Building opportunities.

PMID- 24860875
TI  - A quantitative fluorescence-based steady-state assay of DNA polymerase.
AB  - Fluorescent dyes that bind DNA have been demonstrated as a useful alternative to
      radionucleotides for the quantification of DNA and the in vitro measurement of
      the activity of DNA polymerases and nucleases. However, this approach is
      generally used in a semi-quantitative way to determine relative rates of
      reaction. In this report, we demonstrate a method for the simultaneous
      quantification of DNA in both its single-strand and double-strand forms using the
      dye PicoGreen. This approach is used in a steady-state assay of DNA polymerase
      Klenow fragment exo(-), where we determine kcat and Km values for the DNA
      polymerase that are in excellent agreement with literature values.

PMID- 24860877
TI  - Authors' reply.

PMID- 24860878
TI  - Still much to learn about mice.

PMID- 24860880
TI  - Out with a bang.

PMID- 24860879
TI  - Not on the label.

PMID- 24860881
TI  - Reproduction and the world's future.

PMID- 24860882
TI  - Mental health: A road map for suicide research and prevention.

PMID- 24860884
TI  - Tackling ataxia.

PMID- 24860883
TI  - Lifeline: Bart van der Worp.

PMID- 24860885
TI  - "Russell-like" bodies in Philadelphia  chromosome-positive B-lymphoblastic 
      leukemia.

PMID- 24860886
TI  - Hemophagocytic lymphohistiocytosis and  disseminated histoplasmosis.

PMID- 24860887
TI  - Eric Nightingale Campbell Milne, M.B., Ch.B. 1929-2013.

PMID- 24860888
TI  - Pharma corruption.

PMID- 24860890
TI  - A double-edged sword.

PMID- 24860889
TI  - Inhaled mannitol and cystic fibrosis. Unnecessary bronchial irritation.
AB  - Cystic fibrosis is a life-threatening genetic disease mainly characterised by
      accumulation of viscous secretions in the airways. In the absence of a better
      alternative, inhaled dornase alfa is used to liquefy bronchial secretions and
      thereby facilitate their drainage. Mannitol, in the form of capsules of powder
      for inhalation, is authorised in the European Union for use as a mucolytic in
      adults with cystic fibrosis. Two double-blind randomised trials have compared two
      doses of inhaled mannitol (400 mg or 50 mg, twice a day) in a total of 642
      patients (57% adults) with cystic fibrosis. After 26 weeks of treatment, there
      was no difference between the groups in terms of clinical criteria such as the
      frequency of pulmonary exacerbations, quality of life, hospitalisation, or rescue
      antibiotic use. Inhaled mannitol increases the risk of bronchospasm and can also
      cause coughing and haemoptysis. A pretreatment test, used to exclude patients
      with bronchial hyperresponsiveness to mannitol, can also have noteworthy adverse
      effects. Treatment is inconvenient, requiring inhalation of the contents of 10
      mannitol capsules morning and evening; the capsules have to be placed one by one
      in the inhalation device, and the device must be replaced every week. In
      practice, patients with cystic fibrosis would be well advised to avoid inhaled
      mannitol.

PMID- 24860891
TI  - Decitabine. Acute myeloid leukaemia: no progress.
AB  - Acute myeloid leukaemia is a life-threatening disease. Its incidence increases
      with age. There is no consensus on treatment for patients over 60 years of age
      who cannot receive first-line high-dose chemotherapy. Options include low-dose
      cytarabine, other non-intensive chemotherapy regimens, or tailored supportive
      care. Decitabine, a cytotoxic drug related to cytarabine, has been authorised for
      patients aged 65 years or older who are not eligible for intensive chemotherapy.
      Clinical evaluation of decitabine in this setting is mainly based on an unblinded
      randomised controlled trial including 485 patients, who received either
      decitabine, or low-dose cytarabine or symptomatic treatment alone. There was no
      statistically significant difference in overall survival between the two active
      treatment groups (median about 6 months). Serious adverse events occurred in 80%
      of patients in the decitabine group, compared to 73% of those in the cytarabine
      group. They consisted mainly of haematological disorders (neutropenia,
      thrombocytopenia, anaemia), infections (pneumonia) and gastrointestinal
      disorders. In practice, for patients at least 65 years of age with acute myeloid
      leukaemia who are not candidates for intensive chemotherapy, decitabine has no
      advantages over existing treatments in terms of survival time or adverse effects.
      Low-dose cytarabine or tailored supportive care are better-assessed options.

PMID- 24860892
TI  - INN common stem: -afil.

PMID- 24860894
TI  - Tadalafil and benign prostatic hypertrophy. Too risky.
AB  - The vasodilatory effects of tadalafil can provoke serious adverse effects and
      numerous drug-drug interactions. Tadalafil has modest symptomatic efficacy at
      best.

PMID- 24860893
TI  - Pertuzumab. Promising for some women with metastatic breast cancer, but more
      assessment needed.
AB  - Adding trastuzumab to chemotherapy can prolong overall survival among women with
      metastatic or locally recurrent unresectable breast cancer that overexpresses HER
      2 protein. Pertuzumab (Perjeta, Roche) is a monoclonal antibody that targets HER
      2. It has a different binding site from that of trastuzumab, another anti-HER-2
      antibody. Pertuzumab has been authorised in the European Union as an adjunct to
      the trastuzumab + docetaxel combination. A double-blind randomised placebo
      controlled trial involving 808 carefully selected patients (including two men),
      followed for about 2.5 years, showed that the addition of pertuzumab to
      trastuzumab + docetaxel prolonged overall survival: it was estimated that the 3
      year survival rate increased by 10% to 15%. Median progression-free survival was
      6 months longer in the pertuzumab group. Addition of pertuzumab did not aggravate
      cardiac toxicity among patients with a low cardiovascular risk at baseline. In
      contrast, adding pertuzumab increased the incidence of potentially severe
      diarrhoea, mucocutaneous disorders (rash, dry skin, mucosal inflammation) and
      febrile neutropenia. In practice, these results are interesting but they must be
      confirmed in other comparative trials before recommending routine use of
      pertuzumab.

PMID- 24860895
TI  - Drug-induced corneal damage.
AB  - Corneal damage can have a variety of causes, including infections, chemical
      splashes, environmental factors (radiation, trauma, contact lenses, etc.), and
      systemic diseases (genetic, autoimmune, inflammatory, metabolic, etc.). A wide
      range of drugs can also damage the cornea. The severity of drug-induced corneal
      changes can range from simple asymptomatic deposits to irreversible, sight
      threatening damage. Several factors can influence the onset of corneal lesions.
      Some factors, such as the dose, are treatment-related, while others such as
      contact lenses, are patient-related. A variety of mechanisms may be involved,
      including corneal dryness, changes in the corneal epithelium, impaired wound
      healing and deposits. Many drugs can damage the cornea through direct contact,
      after intraocular injection or instillation, including VEGF inhibitors, anti
      inflammatory drugs, local anaesthetics, glaucoma drugs, fluoroquinolones, and
      preservatives. Some systemically administered drugs can also damage the cornea,
      notably cancer drugs, amiodarone and isotretinoin. Vulnerable patients should be
      informed of this risk if they are prescribed a drug with the potential to damage
      the cornea so that they can identify problems in a timely manner. It may be
      necessary to discontinue the suspect drug when signs and symptoms of corneal
      damage occur.

PMID- 24860896
TI  - Drug-induced acute pancreatitis.

PMID- 24860897
TI  - Quetiapine: ischaemic colitis.

PMID- 24860898
TI  - Rotavirus vaccines and intussusception.

PMID- 24860899
TI  - Methylergometrine: adverse effects in breastfed infants.

PMID- 24860900
TI  - Olmesartan: sprue-like enteropathy.
AB  - Olmesartan exposes patients to the risk of sometimes serious chronic intestinal
      disorders with diarrhoea (sprue-like enteropathy). As of late 2013, this adverse
      effect has not been reported with other angiotensin II receptor blockers (ARBs).

PMID- 24860901
TI  - Oncology and haematology in 2013. Some advances, but too many new treatments with
      an inadequately assessed harm-benefit balance.

PMID- 24860902
TI  - Drugs to exclude from your list.

PMID- 24860903
TI  - News products to avoid.

PMID- 24860904
TI  - Treating blood pressure between 140/90 and 160/95 mmHg: no proven benefit.
AB  - According to a systematic review of four randomised trials in 8912 patients,
      antihypertensive therapy has not been shown to have a positive harm-benefit
      balance in people with blood pressure between 140/90 mmHg and 159/99 mmHg, but
      with no other cardiovascular risk factors.

PMID- 24860905
TI  - New drugs and indications in 2013: little real progress but regulatory
      authorities take some positive steps.
AB  - 2013 saw few therapeutic innovations that really benefitted patients; once again,
      marketing authorisations were too often granted despite inadequate clinical data.
      The French health authorities implemented a few measures designed to protect
      patients from dangerous drugs, including market withdrawals, restrictions on use,
      and delisting.

PMID- 24860906
TI  - Clinical trial rigging: again!

PMID- 24860907
TI  - Warning: dangers of insulin at 200 units per ml.

PMID- 24860908
TI  - Prolonging life and suffering.

PMID- 24860909
TI  - David A. Mrazek, MD, FRCPsych (1947-2013).

PMID- 24860910
TI  - Clinical usefulness of novel tag-less Agile patency capsule prior to capsule
      endoscopy for patients with suspected small bowel stenosis.
AB  - BACKGROUND AND AIM: The Agile patency capsule (PC; Given Imaging Ltd, Yoqneam,
      Israel) is used as a dummy prior to capsule endoscopy (CE) to avoid retention of
      the CE capsule. However, impaction of the PC's inner radio frequency
      identification (RFID) tag in a stricture could cause small-bowel ileus. Recently,
      the RFID tag-less PC was introduced into clinical practice. Herein, we aimed to
      retrospectively evaluate the usefulness of the tag-less PC. METHODS: Of 154
      patients who were scheduled to undergo CE, 100 consecutive patients (65%) who
      underwent PC evaluation were enrolled in the present study. Primary study end
      point was the retention rate of the CE capsule after successful passage of the
      PC. Secondary end point was analysis of the significant factors affecting the
      passage of the PC. RESULTS: In total, 87 patients (87%) had bowel patency
      confirmed by PC evaluation. There was no capsule retention in any of these 87
      patients during CE. Abnormal findings were obtained from 60 CE, and 41 patients
      received new or modified treatment. Multivariate analysis of factors related to
      the confirmation of patency demonstrated that stenosis on imaging was the most
      influential factor (P = 0.002, odds ratio 16.387). The results confirmed that
      passage of the PC depends on stenosis on imaging. CONCLUSIONS: Use of the tag
      less PC confirmed gastrointestinal tract patency for most of the patients who did
      not have stenosis on imaging and allowed estimation of the patency for patients
      who did have stenosis on imaging.

PMID- 24860911
TI  - Changes in joint kinetics during learning the longswing on high bar.
AB  - Biomechanics helps us understand the association between technique changes and
      performance improvement during learning. The aim of this research was to
      investigate joint kinetic characteristics of technique during learning of the
      longswing on the high bar. Twelve male, novice participants took part in the
      learning study. During swing attempts in 8 weekly testing sessions, kinematic
      data were collected. Inverse dynamics analysis was performed from known zero
      forces at the toes to quantify joint moments and power at the hips and shoulders.
      Key biomechanical constraints that limited performance outcome were identified
      based on changes in joint kinetics during learning. These constraints were the
      ability to perform a large shoulder power and to overcome passive kinetics acting
      during the downswing. Constraints to action at the level of joint kinetics
      differentially challenge learners and therefore could underpin more individual,
      specific learning interventions. Functional phases, defined by maximum
      hyperextension to flexion of the hips and maximum flexion to extension of the
      shoulders, did not describe the key joint kinetics of the hip and shoulder for
      novices. The functional phases may serve however to identify novices that were
      unable to overcome the passive kinetic constraint.

PMID- 24860912
TI  - Assessment of autonomic functions in children with familial Mediterranean fever
      by using heart rate variability measurements.
AB  - AIM: The aim of this study is to analyze possible autonomic nerve system
      alterations and assess the efficacy of heart rate variability (HRV) analysis in
      anticipation of cardiovascular risks in pediatric patients with familial
      Mediterranean fever (FMF). METHOD: In this study, cardiac autonomic functions
      were investigated in children with FMF by analyzing HRV and its other probable
      cardiac effects by echocardiography. We studied 70 pediatric patients with FMF
      and 50 healthy controls. RESULTS: The time-domain parameters of HRV were compared
      between the FMF and control groups. SDNN (standard deviation of all NN intervals)
      was significantly decreased in patients with FMF as compared to control subjects.
      The other time-domain parameters of HRV and the frequency-domain parameters of
      HRV were similar in both groups. Frequency-dependent HRV parameters were similar
      in both groups, as were conventional echocardiographic parameters. CONCLUSION:
      HRV is a convenient and reliable technique for evaluation of autonomic functions.
      There are only a few studies on the assessment of autonomic functions by means of
      HRV in adult FMF patients but not in pediatric patients. Further studies are
      required to assess whether there is autonomic dysfunction in children with FMF.

PMID- 24860913
TI  - CFD based simulation of thoron ((220)Rn) concentration in a delay chamber for
      mitigation application.
AB  - The release of (220)Rn gas (conventionally referred to as thoron) is an issue of
      concern from the radiological point of view for occupational environments
      pertaining to the thorium fuel cycle. Studies for understanding its release and
      developing systems to control it are crucial for exposure control research. A
      thorough study of the "Delay Volume Technique" for mitigation of (220)Rn has been
      carried out. Experiments have been carried out with (220)Rn source and associated
      measurement system in a cubical chamber (delay chamber) of 0.5 m(3) volume. For
      different flow conditions and inlet-outlet positions, (220)Rn transmission factor
      has been obtained. Computational Fluid Dynamics (CFD) technique has been employed
      for these experimental conditions and the simulated transmission factors have
      been compared. The results show that the flow and the position of the inlet and
      outlet play an imperative role in the transportation, mixing and subsequent
      mitigation of thoron inside the chamber. Predictive capability of CFD technique
      for such delay volume experiments has been validated in this work. A comparison
      has been made with uniform mixing model and it is found that the results of
      simulation differ appreciably from that of uniform mixing model at the tested
      flow regime. 

PMID- 24860914
TI  - Risk of thromboembolism and fatal stroke in patients with psoriasis and
      nonvalvular atrial fibrillation: a Danish nationwide cohort study.
AB  - OBJECTIVES: Psoriasis is a chronic inflammatory disease that is associated with a
      prothrombotic state and cardiovascular disease, including atrial fibrillation and
      thromboembolism. We therefore evaluated the impact of psoriasis in patients with
      atrial fibrillation and the performance of the CHA2 DS2 VASc score in these
      patients. DESIGN, SETTING AND PARTICIPANTS: The study comprised all Danish
      patients hospitalized with nonvalvular atrial fibrillation in the period 1997
      2011 (n = 99,357). Follow-up started 7 days from discharge and excluded subjects
      treated with anticoagulation. Poisson regression adjusted for CHA2 DS2 VASc score
      was used to estimate the incidence rate ratios and 95% confidence intervals. MAIN
      OUTCOME MEASURE: Hospitalization or death from thromboembolism. RESULTS: Mean
      follow-up was 3.5, 3.1, and 2.8 years for patients with no psoriasis, mild
      psoriasis and severe psoriasis, respectively. Patients with psoriasis were
      younger compared to patients without psoriasis, but CHA2DS2VASc score did not
      differ between the three groups. Thromboembolism rates per 100 patient-years (95%
      confidence intervals) were 4.8 (4.7-4.9), 4.8 (4.2-5.4) and 6.1 (5.0-7.5) for
      patients with no psoriasis, mild psoriasis and severe psoriasis, respectively.
      Importantly, the observed thromboembolism rates in patients with severe psoriasis
      were markedly higher (2.6- to3.4-fold) than predicted by the CHA2 DS2 VASc score.
      Relative to no psoriasis, incidence rate ratios were 0.99 (0.87-1.11) and 1.27
      (1.02-1.57) for mild and severe psoriasis, respectively. Correspondingly,
      incidence rate ratios for fatal stroke were 0.97 (0.80-1.12) and 1.51 (1.12
      2.05). CONCLUSIONS: In patients with nonvalvular atrial fibrillation not treated
      with oral anticoagulation, severe psoriasis was associated with increased risk of
      thromboembolism. In these patients, CHA2 DS2 VASc underestimated the risk of
      thromboembolism.

PMID- 24860915
TI  - [More on the Royal Decree-law 16/2012 and its urgent measures to guarantee the
      sustainability of the National Health System in Spain].

PMID- 24860917
TI  - Correlation of maximum breast carcinoma dimension on needle core biopsy and
      subsequent excisional biopsy: a retrospective study of 50 non-palpable imaging
      detected cases.
AB  - AIMS: There are scant data on the correlation of maximum tumor dimension (MTD) in
      needle core biopsy (NCB) and in subsequent excisional biopsy (EXB) with various
      pre-NCB imaging studies (VIS)-especially in the context of screen-detected
      invasive carcinoma (SIC). METHODS AND RESULTS: Retrospectively studied were
      consecutive (2012-2013) non-palpable, SIC diagnosed on NCB with subsequent EXB.
      Data on MTD on VIS (either mammogram, or ultrasound, or MRI), NCB and EXC were
      analyzed. Mean MTD on VIS was 12.5mm (range: 0-45 mm). Mean MTD on NCB was 6.7 mm
      (range: 1-15 mm). Mean residual MTD on EXB was 12.9 mm (range: 0-40 mm). Mean
      number of NCB performed per SIC was 5 (range: 1-13). Overall, 81% of all NCB were
      involved by SIC. The difference between MTD at EXC and VIS was statistically not
      significant (p>0.05). Spearman correlation coefficient for MTD on VIS and EXC was
      r=0.8718 (p<0.0001) showing a significant correlation. The mean tissue volume
      procured on NCB-calculated by using Aperio whole slide scanning and NIH Image J
      image analysis was 95.5mm(3) (range: 4.3-887.5mm(3), median: 23 mm(3)). A Bland
      Altman plot showed that MTD of >= 7 mm on EXB is a useful cut-off point
      predictive of (any) increase in MTD at EXB. Six of the 13 patients with MTD< 7mm
      on EXB showed a decrease in size; while no patient with MTD on EXB that was >= 7
      mm showed any decrease in size. (Fisher's exact test, P=0.001, two-tailed).
      Overall 88% (44 out of 50 patients) of SIC showed no decrease in MTD on EXB, with
      an increase by >= 4 mm in size (sufficient to upstage "T") in MTD of >= 7mm on
      EXB in 75.6% (28 of 37 patients with MTD of >= 7 mm on EXB). 20.8% of SIC (5 of
      24 patients) that were < 7 mm on NCB (with a mean combined Nottingham grade score
      of 5 {r: 4-6} showed decrease in MTD at EXB. CONCLUSIONS: In this pilot study of
      SIC, (i) MTD on VIS was predictive of MTD on EXB, (ii) MTD of >= 7 mm on NCB was
      predictive of an increased MTD on EXB in most cases, with potential for
      "upstaging" tumors, and (iii) MTD of < 7 mm on NCB was predictive of decreased
      MTD on EXB in 20.8% of (mostly grade I) SIC. Procured tissue volume on NCB
      contributed to decrease in MTD on EXB in small, low-grade carcinomas.

PMID- 24860916
TI  - Well-differentiated papillary mesothelioma manifesting in a hernia sac.
AB  - Well-differentiated papillary mesothelioma (WDPM) is a tumor of uncertain
      malignant potential that usually occurs as a multifocal lesion of the female
      peritoneum, and is incidentally found at the time of surgery. We present here a
      multifocal case that had arisen from the lining of a hernia sac. To our
      knowledge, only four cases of this event have been previously described. A review
      of the five cases reported, including our case, revealed that the mean age of the
      patients was 56.6+/-8.35 years. There was predominance in men (4:1). In four
      cases, the lesion was incidental. Most tumors were found in inguinal hernias.
      Four cases presented with gross abnormalities in the hernia sac. All the five
      patients were alive with no evidence of WDPM after a mean follow-up of 38.6
      months. Extensive sampling of this rare lesion helps to rule out an epithelial
      malignant mesothelioma and prevents overtreatment.

PMID- 24860918
TI  - Large hyperpigmented macule on the leg of an adolescent girl.

PMID- 24860920
TI  - Epidemiology of dental caries in children in the United Arab Emirates.
AB  - Dental caries has a significant impact on the general health and development of
      children. Understanding caries epidemiology is an essential task for the United
      Arab Emirates (UAE) policymakers to evaluate preventive programmes and to improve
      oral health. The purpose of this review is to collect and summarise all data
      available in the published literature on the epidemiology of dental caries in the
      UAE in children aged under 13 years. This will provide dental health planners
      with a comprehensive data summary, which will help in the planning for and
      evaluation of dental caries prevention programmes. Data were collected from the
      various published studies in PubMed, Academic Search Complete, Google, and the
      reference lists in relevant articles. Four keywords were used in the search:
      'dental caries,' 'epidemiology,' 'prevalence,' and 'UAE'. All studies conducted
      in the UAE in general or any single emirate that sheds light on the prevalence of
      dental caries of children under 13 years were included in this literature review.
      Studies on early childhood caries and factors associated with dental caries were
      also included. The review comprises 11 published surveys of childhood caries in
      UAE. The earliest study was published in 1991 and the most recent was published
      in 2011. The range of decayed, missing and filled primary teeth (dmft) in UAE
      children (age between 4 years and 6 years) was 5.1-8.4. For the 12-year-old group
      the decayed missing and filled permanent teeth (DMFT) ranged from 1.6 to 3.24.
      Baseline data on oral health and a good understanding of dental caries
      determinants are necessary for setting appropriate goals and planning for
      preventive oral health programmes. The current data available on the dmft and
      DMFT indicate that childhood dental caries is still a serious dental public
      health problem in the UAE that warrants immediate attention by the government and
      policy makers.

PMID- 24860921
TI  - Primary immunodeficiency disorders: general classification, new molecular
      insights, and practical approach to diagnosis and treatment.

PMID- 24860922
TI  - Epinephrine preparedness in pediatric patients with food allergy: an ideal time
      for change.

PMID- 24860919
TI  - Occupational allergic contact dermatitis and major allergens in France: temporal
      trends for the period 2001-2010.
AB  - BACKGROUND: Occupational allergic contact dermatitis (OACD) is one of the most
      common occupational skin diseases in developed countries, but data about its
      temporal trends in incidence remain sparse. OBJECTIVES: The aim of this study is
      to describe OACD trends in terms of industrial activities and main causal agents
      in France over the period 2001-2010. MATERIALS AND METHODS: Data were collected
      from the French National Network of Occupational Disease Vigilance and Prevention
      (RNV3P, Reseau National de Vigilance et de Prevention des Pathologies
      Professionnelles). All OACD considered probably or certainly associated with an
      occupational exposure were included in the study. Trends were examined (i) on
      annual crude numbers of OACD and (ii) on reported odds ratios of OACD calculated
      using logistic regression models. RESULTS: Overall, 3738 cases of OACD were
      reported and the mean age of OACD cases was 35 years, 52% being women. The most
      frequent occupations were hairdressers, health care workers, cleaning staff and
      masons. The total number of OACD cases remained stable over the study period, but
      increases in OACD related to isothiazolinones (P = 0.002), epoxy resins (P =
      0.012) and fragrances (P = 0.005) were observed. Conversely, decreases were noted
      for cement compounds (P = 0.002) and plant products (P = 0.031). These trends
      highlight specific sectors and exposures at risk of OACD. CONCLUSIONS: Trends in
      OACD depend on the nature of exposure. Observed decreases were consistent with
      prevention measures taken during the study period, and the increases observed
      serve to highlight those areas where preventative efforts need to be made to
      reduce skin allergies in the workplace.

PMID- 24860923
TI  - Allergen of the month--rabbit.

PMID- 24860924
TI  - Large-area, freestanding, single-layer graphene-gold: a hybrid plasmonic
      nanostructure.
AB  - Graphene-based plasmonic devices have recently drawn great attention. However,
      practical limitations in fabrication and device architectures prevent studies
      from being carried out on the intrinsic properties of graphene and their change
      by plasmonic structures. The influence of a quasi-infinite object (i.e., the
      substrate) on graphene, being a single sheet of carbon atoms, and the plasmonic
      device is overwhelming. To address this and put the intrinsic properties of the
      graphene-plasmonic nanostructures in focus, we fabricate large-area,
      freestanding, single-layer graphene-gold (LFG-Au) sandwich structures and Au
      nanoparticle decorated graphene (formed via thermal treatment) hybrid plasmonic
      nanostructures. We observed two distinct plasmonic enhancement routes of graphene
      unique to each structure via surface-enhanced Raman spectroscopy. The localized
      electronic structure variation in the LFG due to graphene-Au interaction at the
      nanoscale is mapped using scanning transmission X-ray microscopy. The
      measurements show an optical density of ~0.007, which is the smallest
      experimentally determined for single-layer graphene thus far. Our results on
      freestanding graphene-Au plasmonic structures provide great insight for the
      rational design and future fabrication of graphene plasmonic hybrid
      nanostructures. 

PMID- 24860926
TI  - GERD: office-based diagnosis of GERD within spitting distance?

PMID- 24860925
TI  - Functional expression of the Acanthamoeba castellanii alternative oxidase in
      Escherichia coli; regulation of the activity and evidence for Acaox gene
      function.
AB  - To evidence Acanthamoeba castellanii alternative oxidase (AcAOX) gene product
      function, we studied alterations in the levels of mRNA and protein and AcAOX
      activity during growth in amoeba batch culture. Moreover, heterologous expression
      of AcAOX in AOX-deficient Escherichia coli confirmed by the protein
      immunodetection and functional studies was performed. Despite the presence of
      native bo and bd quinol oxidases in E. coli membrane, from which the latter is
      known to be cyanide-resistant, functional expression of AcAOX in E. coli
      conferred cyanide-resistant benzohydroxamate-sensitive respiration on the
      bacteria. Moreover, AcAOX activity in transformed bacteria was stimulated by GMP
      and inhibited by ATP, indicating that AcAOX is regulated by mutual exclusion of
      purine nucleotides, which was previously demonstrated in the mitochondria of A.
      castellanii. 

PMID- 24860927
TI  - Progression of Barrett oesophagus: role of endoscopic and histological
      predictors.
AB  - Barrett oesophagus is an important precursor lesion for the development of
      oesophageal adenocarcinoma (OAC). Upper gastrointestinal endoscopy is the
      modality most widely used to visualize and biopsy the oesophagus to establish a
      diagnosis. Additional clues are available at the time of endoscopy that can
      identify high-risk features known to increase the risk of progression to OAC,
      such as the length of the Barrett oesophagus segment, length of hiatal hernia and
      the presence of nodularity or visible endoscopic lesions in this segment. Until
      molecular biomarkers are identified and validated as adjunctive tools for risk
      stratification, knowledge of endoscopic features could complement dysplasia
      grading for risk stratification of patients with Barrett oesophagus and identify
      subgroups at risk of progression to OAC. This approach would, in turn, facilitate
      more rational tailoring of endoscopic surveillance. This Review summarizes the
      current role of endoscopic and histological factors involved in neoplastic
      progression of Barrett oesophagus to OAC, and provides an overview of the risk
      prediction models that have utilized endoscopic and histological factors for risk
      stratification in patients with Barrett oesophagus. 

PMID- 24860928
TI  - Advances in the endoscopic management of common bile duct stones.
AB  - Extraction of common bile duct stones by endoscopic retrograde
      cholangiopancreatography generally involves biliary sphincterotomy, endoscopic
      papillary balloon dilation or a combination of both. Endoscopic papillary large
      balloon dilation after sphincterotomy has increased the safety of large stone
      extraction. Cholangioscopically directed electrohydraulic and laser lithotripsy
      using single-operator mother-daughter systems or direct peroral cholangioscopy
      using ultraslim endoscopes are increasingly utilized for the management of
      refractory stones. In this Review, we focus on advances in endoscopic approaches
      and techniques, with a special emphasis on management strategies for 'difficult'
      common bile duct stones. 

PMID- 24860929
TI  - Endoscopy: NOTES reveals obscure origin of ascites.

PMID- 24860930
TI  - Genetics: revealing the genomic landscape of gastric cancer.

PMID- 24860931
TI  - The superficial outside-flap shunt (SOS) technique for free deep inferior
      epigastric perforator flap salvage.
AB  - A common cause for loss of a deep inferior epigastric perforator (DIEP) flap is
      venous congestion secondary to inadequate outflow via the deep perforating
      vessels. Further anastomosis of the superficial venous system provides effective
      outflow and salvage of the congested DIEP. Multiple methods have been described
      requiring dissection of additional recipient venous systems or around the
      perforating vessels in order to provide a vein onto which the superficial system
      may be anastomosed. These are potentially associated with increased morbidity and
      risk of damage to the pedicle. We describe an alternative technique of harvesting
      an additional length of deep inferior epigastric pedicle cranial to the
      perforator onto which an anastomosis may be performed. This avoids the need for
      additional dissection of recipient vessels or further handling of the perforator,
      its venae comitantes and the main pedicle of the flap thus reducing the risk of
      damage. 

PMID- 24860932
TI  - A comparison of the patient and surgeon opinion on the long-term aesthetic
      outcome of reduction mammaplasty: have we improved over 15 years?
AB  - In 1996 we published a study evaluating the difference between patient and
      surgeon opinion on the aesthetic outcome of reduction mammaplasty (see Ref. 1).
      The patients rated the aesthetic outcome of their surgery as significantly higher
      than the consultant panel. The surgical panel suggested scope for improvement.
      Areas of dissatisfaction were poor scarring, high placement of the nipple areola
      complex and high rates of revision surgery. Fifteen years on, the same team has
      regrouped to repeat this assessment. In 1996 the consultants scored their own
      patient results. In 2011 they graded the results of their former trainee who has
      modified her operative technique to address aesthetic problems highlighted in the
      first study. Forty-four patients attended a review clinic at least one year post
      reduction mammaplasty. Patient scored their satisfaction using the original
      questionnaire employed in 1996. The cohort were photographed and their images
      graded blindly by the original surgical panel. Statistical analysis was performed
      by the original statistician. The patients graded aesthetic aspects of body
      harmony, breast mound appearance, nipple areolar complex appearance and post
      operative scarring significantly more positively (p<0.01) than both the 1996
      patient cohort and surgical panel. The consultant panel showed a trend for more
      positive grades for all aesthetic features assessed versus their previous views
      but this was only significant for breast mound symmetry. They expressed that
      there was a decrease in post-operative breast ptosis (p<0.04) and improvement in
      the nipple areolar complex position (p=0.02). The rate of revision surgery has
      decreased from 53% to 16% between the studies. In keeping with clinical audit,
      outcomes have been assessed and modifications implemented to address aesthetic
      concerns. Assessment of outcomes following the modifications demonstrates a trend
      for increased patient and surgeon satisfaction. Patient satisfaction however
      still exceeds that of the surgeons.

PMID- 24860933
TI  - Toxic epidermal necrolysis (TEN): the Chelsea and Westminster Hospital wound
      management algorithm.
AB  - Toxic epidermal necrolysis syndrome (TEN) is a potentially catastrophic
      exfoliative muco-cutaneous disorder first described by Lyell in 1956. It
      represents the most extensive form of Steven-Johnson syndrome. TEN is defined
      varyingly around the globe, but in the United Kingdom the consensus opinion
      describes the process as involving >30% of the total body surface area. It can
      rapidly become more extensive and threatens life. The estimated annual incidence
      is approximately 1-2 cases per million population. The risk of mortality
      increases with surface area involved and meta-analysis of the literature shows
      this risk to be between 16% and 55%. Over a six month period the Chelsea and
      Westminster Hospital Burns Service treated five consecutive patients with more
      than 80% total body surface area involvement or a more than 80% mortality risk,
      using the severity-of-illness score for toxic epidermal necrolysis (SCORTEN). All
      patients were treated according to the Chelsea and Westminster Hospital wound
      management algorithm with excellent outcome and no mortalities. The aim of this
      paper is to propose a generic TEN wound management algorithm according to the
      severity of skin lesions, using a simple wound grading system. 

PMID- 24860934
TI  - Effect of endurance training on expiratory flow limitation and dynamic
      hyperinflation in patients with stable chronic obstructive pulmonary disease.
AB  - BACKGROUND: Expiratory flow limitation (EFL) is the primary pathophysiological
      hallmark of chronic obstructive pulmonary disease (COPD). However, the effect of
      lower-extremity endurance training alone on EFL in patients with COPD remains
      largely unknown. AIM: This study aims to determine the effects of endurance
      training on EFL and dynamic hyperinflation in patients with stable COPD. METHODS:
      This was a prospective, single-blinded, non-randomised controlled 12-week study
      recruiting Chinese patients with stable COPD in an endurance training group (n =
      15) or a control group (n = 13). Before and at the end of the study, we measured
      the EFL, pulmonary function, peak inspiratory flow (PIF) and maximum inspiratory
      pressure (MIP); moreover, the patients underwent a constant work rate exercise
      test in which Borg dyspnoea scale, tidal breathing flow volume curves and
      inspiratory capacity (IC) were determined every other minute. RESULTS: Exercise
      training significantly improved the exercise endurance time (7.00 +/- 3.05 vs
      18.13 +/- 6.44 min, P < 0.001), MIP (69.49 +/- 16.03 vs 80.18 +/- 15.97 cmH2 O, P
      < 0.001) and PIF (3.96 +/- 1.01 vs 4.51 +/- 1.13 L/s, P = 0.014), but not EFL
      (3.33 +/- 0.49 vs 3.40 +/- 0.51, P = 0.334). Subjects on training had decreased
      breathing frequency (26.26 +/- 7.13 vs 23.15 +/- 5.34 breaths/min, P = 0.002),
      minute ventilation (30.28 +/- 7.52 vs 26.85 +/- 4.17 L, P = 0.013), tidal peak
      expiratory flow (1.53 +/- 0.22 vs 1.32 +/- 0.20 L/s, P = 0.006), mean expiratory
      flow (0.87 +/- 0.19 vs 0.68 +/- 0.15 L/s, P = 0.011) and Borg dyspnoea score
      (7.20 +/- 1.15 vs 3.93 +/- 1.39, P < 0.001), as well as increased IC (1.50 +/-
      0.34 vs 1.67 +/- 0.45 L, P = 0.002), expiratory time (1.47 +/- 0.62 vs 1.72 +/-
      0.62 s, P = 0.004) and inspiratory flow reserve (2.05 +/- 1.10 vs 2.95 +/- 1.19
      L/s, P = 0.002) at isotime. These changes were not observed in the control group.
      CONCLUSION: Endurance training may benefit stable COPD patients in improving
      exercise endurance, inspiratory muscle strength, ventilatory requirements,
      exercise-induced hyperinflation and exertional dyspnoea.

PMID- 24860935
TI  - A technique to measure the intracuff pressure continuously: an in vivo
      demonstration of its accuracy.
AB  - OBJECTIVE: A major concern with the use of cuffed endotracheal tubes (cETT) in
      children is hyperinflation of the cuff which may compromise tracheal mucosal
      perfusion. To measure the intracuff pressure (CP), we devised a method using the
      transducer of an invasive pressure monitoring device. The objective of the study
      was to test the accuracy and validity of this device for instantaneous and
      continuous CP monitoring. METHODS: The study was conducted in 2 phases. In Phase
      1 (200 pediatric patients), after inflation of the cuff, the CP was measured
      using the standard manometer and the transducer simultaneously. In Phase 2 (20
      pediatric patients), the transducer was left connected to the pilot balloon of
      the ETT to obtain a continuous CP reading and the standard manometer was used to
      measure the CP at 5-min intervals. Statistical analysis included a Bland-Altman
      comparison and linear regression analysis. RESULTS: In Phase 1, linear regression
      analysis demonstrated an R2 value of 0.9956. The bias was 0.30 cmH2O, the
      precision was 0.75 cmH2O, and the 95% level of agreement (LOA) ranged from -1.16
      to 1.77 cmH2O. In Phase 2, the linear regression analysis revealed an R2 value of
      0.9846. The bias was 0.28 cmH2O, the precision was 0.7 cmH2O, and the 95% LOA
      ranged from -1.1 to 1.66 cmH2O. CONCLUSION: Our study demonstrates that when
      cETTs are used in the pediatric population, the transducer of the invasive
      pressure monitoring device can be used reliably to measure the CP at the time of
      inflation and continuously thereafter.

PMID- 24860936
TI  - Abstracts of the 21th European Congress on Obesity (ECO2014), May 28-31, 2014,
      Sofia, Bulgaria.

PMID- 24860938
TI  - Evaluation of viable Mycobacterium avium subsp. paratuberculosis in milk using
      peptide-mediated separation and Propidium Monoazide qPCR.
AB  - The causative agent of paratuberculosis in ruminants, Mycobacterium avium subsp.
      paratuberculosis (MAP), although still a matter of debate, has been linked with
      Crohn's and other human diseases. The availability of rapid methods for assessing
      the viability of MAP cells in food, in particular milk, could be of great use for
      risk management in food safety. MAP viability is generally assessed using culture
      techniques that require prolonged incubation periods for the growth of MAP. To
      differentiate between viable and nonviable MAP cells in milk samples, this study
      explores the combination of two already described techniques: peptide magnetic
      bead separation followed by Propidium Monoazide qPCR. Using an Ordinal
      Multinomial Logistic Regression model to analyze the results obtained after
      spiking milk samples with mixtures containing different percentages of
      viable/dead cells, we were able to assess the probability of the viability status
      of MAP found in milk. This model was applied to contaminated pasteurized milk to
      ascertain the efficacy of heat treatment in MAP killing. The method reported
      herein can potentially be used for direct detection of MAP viability in milk.

PMID- 24860937
TI  - gammadelta T cell subsets play opposing roles in regulating experimental
      autoimmune encephalomyelitis.
AB  - gammadelta T cells are resident in cerebrospinal fluid and central nervous system
      (CNS) lesions of multiple sclerosis (MS) patients, but as multifaceted cells
      exhibiting innate and adaptive characteristics, their function remains unknown.
      Previous studies in experimental autoimmune encephalomyelitis (EAE) are
      contradictory and identified these cells as either promoting or suppressing
      disease pathogenesis. This study examines distinct gammadelta T cell subsets
      during EAE and indicates they mediate differential functions in CNS inflammation
      and demyelination resulting in pathogenesis or protection. We identified two
      gammadelta subsets in the CNS, Vgamma1(+) and Vgamma4(+), with distinct cytokine
      profiles and tissue specificity. Anti-gammadelta T cell receptor (TCR) monoclonal
      antibody (mAb) administration results in activation and downregulation of surface
      TCR, rendering the cells undetectable, but with opposing effects: anti-Vgamma4
      treatment exacerbates disease whereas anti-Vgamma1 treatment is protective. The
      Vgamma4(+) subset produces multiple pro-inflammatory cytokines including high
      levels of IL-17, and accounts for 15-20% of the interleukin-17 (IL-17) producing
      cells in the CNS, but utilize a variant transcriptional program than CD4(+) Th17
      cells. In contrast, the Vgamma1 subset produces CCR5 ligands, which may promote
      regulatory T cell differentiation. gammadelta T cell subsets thus play distinct
      and opposing roles during EAE, providing an explanation for previous reports and
      suggesting selective targeting to optimize regulation as a potential therapy for
      MS.

PMID- 24860940
TI  - The relative anatomy of the coronary arterial and venous systems: implications
      for coronary interventions.
AB  - An anatomical understanding of human coronary arterial and venous systems is
      necessary for device development and therapy applications that utilize these
      vessels. We investigated the unique use of contrast-CT scans from perfusion-fixed
      human hearts for three-dimensional visualization and analysis of anatomical
      features of the coronary systems. The coronary arterial and venous systems of
      eleven perfusion-fixed human hearts were modeled using contrast-CT and Mimics
      software. The coronary arteries that coursed near the major coronary veins, how
      close coronary arteries were to coronary veins, and the size of adjacent coronary
      arteries were recorded and analyzed. The majority of coronary veins were within 5
      mm of a coronary artery somewhere along its length. Interventricular veins
      elicited the largest occurrence of overlaps. There was significant variability in
      the percentage of each vein that coursed within 0.5, 1, 2, and 5 mm of a nearby
      artery. The left marginal veins and anterior interventricular vein had the
      largest portion of the vein that coursed near a coronary artery. The right
      coronary artery most often coursed near the middle cardiac vein. The inferior
      veins of the left ventricle elicited the most variation in adjacent arteries. The
      left circumflex artery and/or branches of the circumflex artery coursed near the
      left marginal vein in all cases where there was an artery near the marginal vein.
      The wide variation of measurements reinforces the importance of a precise
      understanding of individualized cardiac anatomy in order to provide the highest
      quality care to cardiac patients.

PMID- 24860939
TI  - Inhibition of hypoxia inducible factor 1alpha by siRNA-induced apoptosis in human
      retinoblastoma cells.
AB  - Hypoxia, which activates the hypoxia inducible factor 1alpha (HIF-1alpha), is an
      essential feature of retinoblastoma (RB) and contributes to poor prognosis and
      resistance to conventional therapy. In this study, the effect of HIF-1alpha
      knockdown by small interfering RNA (siRNA) on cell proliferation, apoptosis, and
      apoptotic pathways of human Y-79 RB cells was first investigated. Exposure to
      hypoxia induced the increased expression of HIF-1alpha both in mRNA and protein
      levels. Then, knockdown of HIF-1alpha by siRNAHIF-1alpha resulted in inhibition
      of cell proliferation and induced cell apoptosis in human Y-79 RB cells under
      both normoxic and hypoxic conditions, with hypoxic conditions being more
      sensitive. Furthermore, knockdown of HIF-1alpha could enhance hypoxia-induced
      slight increase of Bax/Bcl-2 ratio and activate caspase-9 and caspase-3. These
      results together indicated that suppression of HIF-1alpha expression may be a
      promising strategy for the treatment of human RB in the future. 

PMID- 24860941
TI  - Landscape genomics and a common garden trial reveal adaptive differentiation to
      temperature across Europe in the tree species Alnus glutinosa.
AB  - The adaptive potential of tree species to cope with climate change has important
      ecological and economic implications. Many temperate tree species experience a
      wide range of environmental conditions, suggesting high adaptability to new
      environmental conditions. We investigated adaptation to regional climate in the
      drought-sensitive tree species Alnus glutinosa (Black alder), using a
      complementary approach that integrates genomic, phenotypic and landscape data. A
      total of 24 European populations were studied in a common garden and through
      landscape genomic approaches. Genotyping-by-sequencing was used to identify SNPs
      across the genome, resulting in 1990 SNPs. Although a relatively low percentage
      of putative adaptive SNPs was detected (2.86% outlier SNPs), we observed clear
      associations among outlier allele frequencies, temperature and plant traits. In
      line with the typical drought avoiding nature of A. glutinosa, leaf size varied
      according to a temperature gradient and significant associations with multiple
      outlier loci were observed, corroborating the ecological relevance of the
      observed outlier SNPs. Moreover, the lack of isolation by distance, the very low
      genetic differentiation among populations and the high intrapopulation genetic
      variation all support the notion that high gene exchange combined with strong
      environmental selection promotes adaptation to environmental cues. 

PMID- 24860942
TI  - Systematic investigation on Cadmium-incorporation in Li2FeSiO4/C cathode material
      for lithium-ion batteries.
AB  - Cadmium-incorporated Li2FeSiO4/C composites have been successfully synthesized by
      a solid-state reaction assisted with refluxing. The effect and mechanism of Cd
      modification on the electrochemical performance of Li2FeSiO4/C were investigated
      in detail by X-ray powder diffraction, X-ray photoelectron spectroscopy, scanning
      electron microscopy, Raman spectra, transmission electron microscopy, positron
      annihilation lifetime spectroscopy and Doppler broadening spectrum, and
      electrochemical measurements. The results show that Cd not only exists in an
      amorphous state of CdO on the surface of LFS particles, but also enters into the
      crystal lattice of LFS. Positron annihilation lifetime spectroscopy and Doppler
      broadening spectrum analyses verify that Cd-incorporation increases the defect
      concentration and the electronic conductivity of LFS, thus improve the Li(+)-ion
      diffusion process. Furthermore, our electrochemical measurements verify that an
      appropriate amount of Cd-incorporation can achieve a satisfied electrochemical
      performance for LFS/C cathode material. 

PMID- 24860944
TI  - Commentary: letter to the editor for "thirty-seven patients treated with the C
      seal: protection of stapled colorectal anastomoses with a biodegradable sheath"
      of Warwick A. et al.

PMID- 24860943
TI  - Long term exposure to L-arginine accelerates endothelial cell senescence through
      arginase-II and S6K1 signaling.
AB  - L-arginine supplementation is proposed to improve health status or as adjunct
      therapy for diseases including cardiovascular diseases. However, controversial
      results and even detrimental effects of L-arginine supplementation are reported.
      We investigate potential mechanisms of L-arginine-induced detrimental effects on
      vascular endothelial cells. Human endothelial cells were exposed to a
      physiological (0.1 mmol/L) or pharmacological (0.5 mmol/L) concentration of L
      arginine for 30 minutes (acute) or 7 days (chronic). The effects of L-arginine
      supplementation on endothelial senescence phenotype, i.e., levels of senescence
      associated beta-galactosidase, expression of vascular cell adhesion molecule-1
      and intercellular adhesion molecule-1, eNOS-uncoupling, arginase-II
      expression/activity, and mTORC1-S6K1 activity were analyzed. While acute L
      arginine treatment enhances endothelial NO production accompanied with superoxide
      production and activation of S6K1 but no up-regulation of arginase-II, chronic L
      arginine supplementation causes endothelial senescence, up-regulation of the
      adhesion molecule expression, and eNOS-uncoupling (decreased NO and enhanced
      superoxide production), which are associated with S6K1 activation and up
      regulation of arginase-II. Silencing either S6K1 or arginase-II inhibits up
      regulation/activation of each other, prevents endothelial dysfunction, adhesion
      molecule expression, and senescence under the chronic L-arginine supplementation
      condition. These results demonstrate that S6K1 and arginase-II form a positive
      circuit mediating the detrimental effects of chronic L-arginine supplementation
      on endothelial cells. 

PMID- 24860945
TI  - Pluripotency in the light of the developmental hourglass.
AB  - The hourglass model of development postulates divergence in early and late embryo
      development bridged by a period of developmental constraint at mid-embryogenesis.
      Recently, molecular support for the hourglass model of development has
      accumulated, with the emphasis on studies using zebrafish and Drosophila species.
      Across mammals, the hourglass model and specifically divergence in early
      development has thus far received little attention. Divergence in mammalian pre
      implantation development is particularly interesting because of its potential
      impact on derivation of pluripotent embryonic stem cells. Here, we review recent
      findings that support the hourglass model of development. We provide striking
      examples of variation in key events in mammalian peri-implantation development
      and their potential consequences for pluripotency of embryonic stem cell lines,
      including mechanisms of cell signalling and differentiation, gene regulatory
      networks, X-chromosome inactivation, and epigenetic regulation. The variation in
      these processes indicates divergence in early mammalian development as was
      postulated by the hourglass model of development. We discuss the naive and primed
      states of pluripotency in light of this developmental divergence and their
      implications for human pluripotent stem cell states. 

PMID- 24860946
TI  - London Health Sciences Centre: raising the CQI bar.

PMID- 24860947
TI  - Continuous quality improvement: a shared governance model that maximizes agent
      specific knowledge.
AB  - Motivate, Innovate, Celebrate: an innovative shared governance model through the
      establishment of continuous quality improvement (CQI) councils was implemented
      across the London Health Sciences Centre (LHSC). The model leverages agent
      specific knowledge at the point of care and provides a structure aimed at
      building human resources capacity and sustaining enhancements to quality and safe
      care delivery. Interprofessional and cross-functional teams work through the CQI
      councils to identify, formulate, execute and evaluate CQI initiatives. In
      addition to a structure that facilitates collaboration, accountability and
      ownership, a corporate CQI Steering Committee provides the forum for scaling up
      and spreading this model. Point-of-care staff, clinical management and educators
      were trained in LEAN methodology and patient experience-based design to ensure
      sufficient knowledge and resources to support the implementation. 

PMID- 24860948
TI  - Reducing waste in the critical care setting.
AB  - BACKGROUND: The ICU at London Health Sciences Centre-University Hospital (LHSC
      UH) is a 40-bed critical care unit that contains two separate supply rooms that
      carry all the essential materials necessary for patient care. However,
      considering the patient acuity in critical care, it is vital that this equipment
      is made more accessible for practitioners at the bedside. Therefore, nurse
      servers or bedside supply cabinets are present in each of the patient rooms.
      While these servers provide timely access to the supplies essential for nursing
      care, they are also a huge source of waste. When patients who are identified as
      having antibiotic-resistant organisms (AROs) are discharged, numerous unused
      items are discarded for infection control purposes. AIMS AND OBJECTIVES: Project
      objectives were to curtail waste by minimizing stocked supplies at the bedside,
      exploring alternative stocking options and increasing awareness of this issue
      with practitioners. METHODS: An interprofessional team was formed consisting of
      registered nurses, support service workers, environmental service workers,
      infection control practitioners and critical care leadership. A cost analysis of
      discarded supplies was undertaken, and results were communicated to all staff.
      Infection control practitioners developed guidelines specific to use of the nurse
      servers and linen supply areas. The stocking process and contents of the servers
      were reviewed; surplus was removed and relocated to a close central area outside
      patient rooms. Following agreement on new server contents, lists and photos were
      created and posted in each supply room. New stocking guidelines were phased in
      gradually and were adapted according to user feedback. RESULTS: Over a two-week
      period, a pilot cost analysis identified that supplies valued at $2,327.25 had
      been discarded from five bedsides. Future long-term cost savings will enable
      management to redirect such resources and therefore improve other essential care
      services in the ICU. CONCLUSION: Increasing awareness of wasteful stocking
      practices facilitated the engagement of this CQI project. New stocking practices
      have greatly reduced waste and increased service efficiencies while maintaining
      the integrity of optimal patient care.

PMID- 24860949
TI  - More than just a simple swish and spit: implementation of oral care best practice
      in clinical neurosciences.
AB  - Suboptimal oral care is well documented in the literature and is linked to
      increased nosocomial pneumonia rates and prolonged hospitalization, negatively
      affecting patients' quality of life (Terezakis et al. 2011). A standardized
      approach to oral care can change these adverse outcomes. This project used best
      practice guidelines and evidence in the literature to guide the development of
      oral care best practice within an acute care inpatient unit. Based on the work of
      the interprofessional Clinical Neurological Sciences (CNS) Continuous Quality
      Improvement (CQI) Council at London Health Sciences Centre-University Hospital
      (LHSC-UH), an oral care policy and bedside assessment tool were implemented in
      line with Stroke Best Practice Recommendations (Heart and Stroke Foundation of
      Canada 2010). A validated, reliable and feasible oral health assessment tool
      (OHAT) was selected for implementation, and is now completed on every patient
      within 24 hours of admission to the CNS inpatient unit. Favourable outcomes to
      date include improved accessibility of oral health supplies, including regular
      and suction toothbrushes, toothpaste and bite blocks. Post-implementation audits
      indicate increased frequency and quality of oral care. This review provides a
      synopsis of how oral care best practice was implemented in an acute care
      neurology/neurosurgery setting.

PMID- 24860950
TI  - Mothers' "liquid gold": a quality improvement initiative to support early
      colostrum delivery via oral immune therapy (OIT) to premature and critically ill
      newborns.
AB  - Early breast milk, known as colostrum ("liquid gold") provides immune benefits to
      infants, offering potential risk reduction for nosocomial infection (NI) and
      necrotizing enterocolitis (NEC), a serious gastrointestinal emergency. Provision
      of colostrum is recognized as oral immune therapy (OIT) and is valuable to all
      NICU infants unable to feed orally. A quality improvement project was initiated
      by the multidisciplinary NICU Quality Care Council at London Health Sciences
      Centres-Victoria (LHSC-VH) to obtain mothers' colostrum for early OIT. The
      initiative was driven by the Canadian EPIQ (Evidence-based Practice for Improving
      Quality) group as a means of reducing the rates of NEC and NI, two major
      morbidities in the NICU. The overall aim was to facilitate the availability of
      OIT to preterm and critically ill neonates as soon as possible after birth. 

PMID- 24860951
TI  - The Lunch Bunch: an innovative strategy to combat depression and delirium through
      socialization in elderly sub-acute medicine patients.
AB  - Hospitalized sub-acute medicine patients face challenges to their functional and
      cognitive abilities as they await transfer to long-term care facilities or return
      home. The Continuous Quality Improvement (CQI) Council, representing a
      multidisciplinary team of healthcare professionals working in the Sub-Acute
      Medicine Unit (SAMU), implemented a twice-weekly lunch program called the Lunch
      Bunch in order to combat depression and delirium in our elderly and cognitively
      impaired patients. The Lunch Bunch initiative includes chaplains, nurses and
      physiotherapists who have provided a framework through which essential
      socialization and exercise for this vulnerable population is facilitated.
      Providing a means for both mental and physical stimulation also allows patients
      to open up and discuss hidden feelings of loneliness and isolation, thereby
      beginning a journey of spiritual and emotional healing. 

PMID- 24860952
TI  - The effectiveness of superficial subcutaneous lidocaine administration prior to
      femoral artery sheath removal.
AB  - The dynamic world of healthcare requires continuous review of practice to ensure
      that patient care aligns with current evidence and best practice. Superficial
      subcutaneous lidocaine injection has been an order option at London Health
      Sciences Centre-University Hospital (LHSC-UH) for use in post-percutaneous
      coronary intervention (PCI) prior to femoral artery sheath removal (FASR). The
      purpose of administering lidocaine is to reduce pain during FASR, subsequently
      enhancing the patient's experience. A critical appraisal was performed by the
      Continuous Quality Improvement-Cardiac Care Council (CQI-CCC) at LHSC-UH,
      evaluating the effectiveness of superficial subcutaneous lidocaine for use in
      patients undergoing FASR. This paper details the process followed to evaluate
      this practice and reports on the subsequent findings and recommendations. A
      literature review, a retrospective chart audit, a blinded online survey and peer
      hospital polling were compiled, and a summary of findings was shared with the
      cardiac interventionists, with subsequent polling. No significant evidence for
      pain reduction was identified when lidocaine injections were administered prior
      to FASR. As such, a unanimous decision was reached to remove lidocaine from the
      LHSC Coronary Angioplasty Clinical Pathway order form.

PMID- 24860954
TI  - Building a healthy work environment: a nursing resource team perspective.
AB  - Leadership and staff from the London Health Sciences Centre (LHSC) Nursing
      Resource Team (NRT), including members of their Continuous Quality Improvement
      (CQI) Council, attended the first Southern Ontario Nursing Resource Team
      Conference (SONRTC), held March 2012 in Toronto. The SONRTC highlighted healthy
      work environments (HWEs), noting vast differences among the province's various
      organizations. Conversely, CQI Council members anecdotally acknowledged similar
      inconsistencies in HWEs across the various inpatient departments at LHSC. In
      fact, the mobility of the NRT role allows these nurses to make an unbiased
      observation about the culture, behaviours and practices of specific units as well
      as cross-reference departments regarding HWEs. Studies have documented that HWEs
      have a direct impact on the quality of patient care. Furthermore, the literature
      supports a relationship between HWEs and nurse job satisfaction. Based on this
      heightened awareness, the NRT CQI Council aimed to investigate HWEs at LHSC. The
      American Association of Critical Care Nurses (AACN) Standards for Establishing
      and Sustaining Healthy Work Environments was adapted in developing a survey for
      measuring HWEs based on the perceptions of NRT staff. Each of the departments was
      evaluated in terms of the following indicators: skilled communication, true
      collaboration, effective decision-making, appropriate staffing, meaningful
      recognition and authentic leadership (AACN 2005). Ultimately, the Building a
      Healthy Work Environment: A Nursing Resource Team Perspective survey was employed
      with NRT nurses at LHSC, and data was collected for use by leadership and staff
      for creating HWE strategies aimed at improving the quality of patient care. 

PMID- 24860953
TI  - Collaborative hospital orientation: simulation as a teaching strategy.
AB  - For nurses, the stress caused by entering a new place of employment may give rise
      to insecurity and a lack of confidence. Lack of confidence in one's nursing
      skills can affect performance and, ultimately, patient care and safety. In
      healthcare, growing fiscal constraints have resulted in lost resources, and
      support for new nursing staff is limited by both time and cost considerations.
      Clinical educators therefore must find innovative ways to provide education and
      support, including creative learning modalities that facilitate nurses'
      transition into a new role and work environment. 

PMID- 24860955
TI  - Coordination of stem and leaf hydraulic conductance in southern California
      shrubs: a test of the hydraulic segmentation hypothesis.
AB  - Coordination of water movement among plant organs is important for understanding
      plant water use strategies. The hydraulic segmentation hypothesis (HSH) proposes
      that hydraulic conductance in shorter lived, 'expendable' organs such as leaves
      and longer lived, more 'expensive' organs such as stems may be decoupled, with
      resistance in leaves acting as a bottleneck or 'safety valve'. We tested the HSH
      in woody species from a Mediterranean-type ecosystem by measuring leaf hydraulic
      conductance (Kleaf) and stem hydraulic conductivity (KS). We also investigated
      whether leaves function as safety valves by relating Kleaf and the hydraulic
      safety margin (stem water potential minus the water potential at which 50% of
      conductivity is lost (Psistem-Psi50)). We also examined related plant traits
      including the operating range of water potentials, wood density, leaf mass per
      area, and leaf area to sapwood area ratio to provide insight into whole-plant
      water use strategies. For hydrated shoots, Kleaf was negatively correlated with
      KS , supporting the HSH. Additionally, Kleaf was positively correlated with the
      hydraulic safety margin and negatively correlated with the leaf area to sapwood
      area ratio. Consistent with the HSH, our data indicate that leaves may act as
      control valves for species with high KS , or a low safety margin. This critical
      role of leaves appears to contribute importantly to plant ecological
      specialization in a drought-prone environment.

PMID- 24860956
TI  - Acute toxicity of mixture of acetaminophen and ibuprofen to Green Neon Shrimp,
      Neocaridina denticulate.
AB  - In recent years, numerous studies have indicated that various long-term use
      drugs, such as antibiotics or analgesics, not only cannot be completely
      decomposed via sewage treatment but also exhibit biological toxicity if they
      enter the environment; thus, the release of these drugs into the environment can
      damage ecological systems. This study sought to investigate the acute toxicity of
      two commonly utilized analgesics, ibuprofen (IBU) and acetaminophen (APAP), to
      aquatic organisms after these drugs have entered the water. To address this
      objective, the acute toxicity (median lethal concentration, LC50, for a 96-h
      exposure) of IBU alone, APAP alone, and mixtures containing different ratios of
      IBU and APAP in green neon shrimp (Neocaridina denticulata) were measured. The
      results of four tests revealed that the 96-h LC50 values for IBU and APAP alone
      were 6.07 mg/L and 6.60 mg/L, respectively. The 96-h LC50 for a 1:1 mixture of
      IBU and APAP was 6.23 mg/L, and the toxicity of this mixture did not
      significantly differ from the toxicity of either drug alone (p<0.05). The
      experimental results for mixtures containing unequal ratios of IBU and APAP
      indicated that mixtures with high APAP concentrations and low IBU concentrations
      exhibited markedly greater toxicity in N. denticulata (LC50=4.78 mg/L) than APAP
      or IBU alone. However, mixtures with high IBU concentrations and low APAP
      concentrations exhibited lower toxicity in N. denticulata (LC50=6.78 mg/L) than
      IBU or APAP alone. This study demonstrated that different mixtures of IBU and
      APAP were associated with different toxic effects in green neon shrimp.

PMID- 24860957
TI  - Therapeutic effect of pectin on octylphenol induced kidney dysfunction, oxidative
      stress and apoptosis in rats.
AB  - Octylphenol (OP) is one of ubiquitous pollutants in the environment. It belongs
      to endocrine-disrupting chemicals (EDC). It is used in many industrial and
      agricultural products. Pectin is a family of complex polysaccharides that
      function as a hydrating agent and cementing material for the cellulose network.
      The aim of this study was to evaluate the therapeutic effect of pectin in kidney
      dysfunction, oxidative stress and apoptosis induced by OP exposure. Thirty-two
      male albino rats were divided into four equal groups; group 1 control was
      injected intraperitoneally (i.p) with saline [1 ml/kg body weight (bwt)], groups
      2, 3 & 4 were injected i.p with OP (50 mg/kg bwt) three days/week over two weeks
      period where groups 3 & 4 were injected i.p with pectin (25 or 50 mg/kg bwt)
      three days/week over three weeks period. The results of the present study
      revealed that OP significantly decreased glutathione-S-transferase (GST),
      glutathione peroxidase (GPx), catalase (CAT), reduced glutathione (GSH),
      glutathione reductase (GR) and superoxide dismutase (SOD) levels while increased
      significantly lipid peroxidation (MDA), nitric oxide (NO) and protein carbonyls
      (PC) levels in the kidney tissues. On the other hand, OP increased serum urea and
      creatinine. Furthermore, OP increased significantly serum uric acid but decreased
      significantly the kidney weight. Moreover, OP decreased p53 expression while
      increased bcl-2 expression in the kidney tissue. The treatment with either dose
      of pectin to OP-exposed rats restores all the above parameters to approach the
      normal values where pectin at higher dose was more effective than lower one.
      These results were supported by histopathological investigations. In conclusion,
      pectin has antioxidant and anti-apoptotic activities in kidney toxicity induced
      by OP and the effect was dose-dependent.

PMID- 24860958
TI  - Studies on the effect of quercetin and nitrates on the redox homeostasis using in
      vitro model.
AB  - Antioxidants are widely considered to be a preventive measure for many diseases
      and beneficial for health. However, an increasing number of reports suggest a
      lack of any influence by antioxidants on health or even harmful pro-oxidative
      effects of antioxidants. In most cases, the research was conducted with respect
      to a chosen antioxidant, without considering the presence of other chemical
      substances present in food, with which these compounds may react. The aim of this
      work was to determine whether and to what extent the simultaneous presence of
      quercetin and sodium nitrate influences oxidative-reductive homeostasis in
      fibroblast cultures. Superoxide dismutase (SOD), glutathione peroxidase (GPx),
      glutathione reductase (GR), and nitric oxide synthase (NOS) activities were
      measured together with nitric oxide (NO) concentration and total antioxidant
      status (TAS). An increase in the activity of all the enzymes measured and in the
      NO concentration was determined compared with the control culture. The most
      prominent changes were observed at the highest quercetin concentration. These
      results indicate that the simultaneous presence of quercetin and sodium nitrate
      disrupts the oxidative-reductive homeostasis in fibroblasts. 

PMID- 24860959
TI  - Immune hemolytic anemia with drug-induced antibodies to carboplatin and
      vincristine in a pediatric patient with an optic pathway glioma.
AB  - BACKGROUND: Drug-induced immune hemolytic anemia (DIIHA) is a rare, but important
      condition requiring specialized laboratory testing for diagnosis. We report a
      case of DIIHA with antibodies against carboplatin and vincristine (VCR) in a
      child with an optic pathway glioma. Platinum-based drugs are established to cause
      DIIHA; to our knowledge, this is the first report implicating VCR. STUDY DESIGN
      AND METHODS: A 35-month-old girl with an optic pathway glioma developed hemolytic
      anemia while receiving carboplatin and VCR. Specialized blood bank testing was
      performed to determine the presence of drug-dependent antibodies and thus DIIHA.
      RESULTS: Initial direct antiglobulin test (DAT) was negative. A repeat DAT 3 days
      later was positive, 3+ with polyspecific-antiglobulin sera, weak+ with anti
      immunoglobulin (Ig)G, and 2+ with anti-C3d. An eluate from the DAT-positive red
      blood cells (RBCs) was nonreactive. The patient's serum reacted without
      specificity to all RBC tested using papain-IgG-antiglobulin test (AGT) and
      polyethylene glycol-IgG-AGT. No alloantibodies to common RBC antigens were
      detected. When the serum was evaluated for the presence of drug-specific
      antibody, reactivity was shown with VCR and carboplatin using the drug addition
      solution method, but only with carboplatin using the drug-coating method.
      CONCLUSION: The patient developed hemolytic anemia during chemotherapy. Initial
      detection of a panagglutinin suggested a warm-type autoimmune process. However,
      since DIIHA could not be excluded, chemotherapy was discontinued and further work
      up was initiated. The findings confirmed the presence of antibodies to
      carboplatin and VCR. This case highlights the importance for clinicians to
      maintain a high index of suspicion for DIIHA in patients with unexplained
      hemolysis and the importance of specialized serologic testing.

PMID- 24860962
TI  - High diabetes risk among asylum seekers in The Netherlands.
AB  - AIMS: To map the prevalence and incidence of recorded diabetes among asylum
      seekers according to demographic factors and length of stay in the host country.
      METHODS: We used a nationwide database from the Community Health Services for
      Asylum Seekers. The study population included all asylum seekers aged 20-79 years
      who arrived in the Netherlands between 2000 and 2008. Case allocation was based
      on International Classification of Primary Care codes. A general practice
      registry was used to obtain reference data. Standardized prevalence and incidence
      ratios were calculated and their association with length of stay was explored
      with Cox regression. RESULTS: The study included 59 380 asylum seekers among whom
      there were 1227 recorded cases of diabetes. The prevalence of recorded diabetes
      was higher among asylum seekers compared with the reference population for both
      men (standardized prevalence ratio=1.85, 95% CI 1.71-1.91) and women
      (standardized prevalence ratio=2.26, 95% CI 2.08-2.45). The highest standardized
      prevalence ratios were found for asylum seekers from Somalia, Sudan and Sri
      Lanka. The standardized prevalence ratio was higher in asylum seekers aged >= 30
      years. Incidence rates were higher compared with the reference population for all
      length-of-stay intervals. CONCLUSIONS: Asylum seekers from the majority of
      countries of origin were at higher risk of diabetes compared with the general
      population in the Netherlands. Asylum seekers from Somalia were particularly at
      risk. This emerging public health issue requires attention from policy-makers and
      care providers.

PMID- 24860963
TI  - Carcinoid abdominal crisis: a case report.
AB  - Over the past 40 years, the incidence of neuroendocrine tumors (NETs) has been
      increasing. Distal small bowel (i.e., midgut) NETs most often cause carcinoid
      syndrome manifested as cutaneous flushing, diarrhea, bronchial constriction, and
      cardiac involvement. Carcinoid abdominal crisis occurs when submucosal tumors
      impede the vascular supply to the gut leading to mesenteric ischemia and
      worsening abdominal pain. Here, we report the case of a young woman with
      progressively worsening abdominal pain.

PMID- 24860964
TI  - Exploring Australian intensive care physicians clinical judgement during Donation
      after Cardiac Death: an exploratory qualitative study.
AB  - BACKGROUND: Donation after Cardiac Death (DCD) is one possible solution to the
      world wide organ shortage. Intensive care physicians are central to DCD becoming
      successful since they are responsible for making the clinical judgements and
      decisions associated with DCD. Yet international evidence shows health care
      professionals have not embraced DCD and are often reluctant to consider it as an
      option for patients. PURPOSE: To explore intensive care physicians' clinical
      judgements when selecting a suitable DCD candidate. METHODS: Using interpretative
      exploratory methods six intensive care physicians were interviewed from three
      hospital sites in Australia. Following verbatim transcription, data was subjected
      to thematic analysis. FINDINGS: Three distinct themes emerged. Reducing harm and
      increasing benefit was a major focus of intensive care physicians during
      determination of DCD. There was an acceptance of DCD if there was clear evidence
      that donation was what the patient and family wanted. Characteristics of a
      defensible decision reflected the characteristics of sequencing, separation and
      isolation, timing, consensus and collaboration, trust and communication to ensure
      that judgements were robust and defensible. The final theme revealed the
      importance of minimising uncertainty and discomfort when predicting length of
      survival following withdrawal of life-sustaining treatment. CONCLUSION: DCD
      decisions are made within an environment of uncertainty due to the imprecision
      associated with predicting time of death. Lack of certainty contributed to the
      cautious and collaborative strategies used by intensive care physicians when
      dealing with patients, family members and colleagues around end-of-life
      decisions, initiation of withdrawal of life-sustaining treatment and the
      discussion about DCD. This study recommends that nationally consistent policies
      are urgently needed to increase the degree of certainty for intensive care staff
      concerning the DCD processes.

PMID- 24860965
TI  - Neurocognitive mechanisms of perception-action coordination: a review and
      theoretical integration.
AB  - The present analysis aims at a theoretical integration of, and a systems
      neuroscience perspective on, a variety of historical and contemporary views on
      perception-action coordination (PAC). We set out to determine the common
      principles or lawful linkages between sensory and motor systems that explain how
      perception is action-oriented and how action is perceptually guided. To this end,
      we analyze the key ingredients to such an integrated framework, examine the
      architecture of dual-system conjectures of PAC, and endeavor in an historical
      analysis of the key characteristics, mechanisms, and phenomena of PACs. This
      analysis will reveal that dual-systems views are in need of fundamental re
      thinking, and its elements will be amalgamated with current views on action
      oriented predictive processing into a novel integrative theoretical framework
      (IMPPACT: Impetus, Motivation, and Prediction in Perception-Action Coordination
      theory). From this framework and its neurocognitive architecture we derive a
      number of non-trivial predictions regarding conative, motive-driven PAC. We end
      by presenting a brief outlook on how IMPPACT might present novel insights into
      certain pathologies and into action expertise.

PMID- 24860966
TI  - Efficacy of different irrigation techniques in the removal of calcium hydroxide
      from a simulated internal root resorption cavity.
AB  - AIM: To evaluate the efficacy of six irrigation techniques to remove calcium
      hydroxide (CH) from a simulated internal root resorption cavity. METHODOLOGY: The
      root canals of 100 single-rooted teeth were prepared using the ProTaper system to
      size F5. The roots were split longitudinally, and standardized simulated internal
      root resorption cavities were prepared in the two root halves. The root halves
      were reassembled, and CH was placed into the root canals, with the exception of
      five teeth that served as the negative control group. Another five teeth (the
      positive control group) were not subjected to the CH removal procedure. Ninety
      teeth were randomly divided into six experimental groups (n = 15), according to
      the final irrigation techniques used: conventional syringe irrigation (CSI),
      CanalBrush (CB), passive ultrasonic irrigation (PUI), self-adjusting file (SAF)
      system, EndoActivator (EA), and apical negative pressure irrigation (EndoVac
      system). Five millilitres of 3% NaOCl and 17% EDTA were used in all experimental
      groups during the CH removal procedure. The amount of remaining CH was evaluated
      under a stereomicroscope at 20 *magnification, using a 4-grade scoring system.
      The data were statistically compared using the Kruskal-Wallis and Mann-Whitney U
      tests (P < 0.05). RESULTS: Remnants of CH in simulated internal root resorption
      cavities were found in all experimental groups. SAF and PUI were superior to the
      other groups (P < 0.05); however, there was no significant difference between the
      SAF and PUI (P > 0.05). There were also no significant differences between the
      CSI, CB, EA and EndoVac groups (P > 0.05). CONCLUSIONS: None of the irrigation
      techniques was able to completely remove CH from a simulated internal root
      resorption cavity.

PMID- 24860967
TI  - Germ-free mice as a model to study effect of gut microbiota on host physiology.
AB  - The alterations in resident gut microbiota seen in chronic gastrointestinal
      disorders have led to an increasing interest in the role of gut bacteria in
      maintaining intestinal barrier function. While acute alterations in colonic
      secretomotor function in response to pathogens have been well described, the
      effect of commensal bacteria on intestinal barrier function and colonic
      secretomotor function still remains poorly understood. Germ-free mice represent a
      model system to study effect of gut microbes on host gastrointestinal physiology.
      The study by Lomasney et al. represents an important step in this direction by
      demonstrating that the colonic secretomotor function is largely preserved in germ
      free mice, hence making them a suitable model to study effect of gut microbiota
      on host function. 

PMID- 24860968
TI  - Treatment for constipation: new and old pharmacological strategies.
AB  - BACKGROUND: Constipation is a very common entity. Despite the high prevalence,
      treatment of constipation remains problematic. PURPOSE: Review the current
      literature on new and existing constipation treatment modalities.

PMID- 24860969
TI  - Is metoclopramide nasal spray an acceptable alternative to its oral form?

PMID- 24860970
TI  - Response to Dr. Lankarani.

PMID- 24860971
TI  - Usability study of clinical exome analysis software: top lessons learned and
      recommendations.
AB  - OBJECTIVES: New DNA sequencing technologies have revolutionized the search for
      genetic disruptions. Targeted sequencing of all protein coding regions of the
      genome, called exome analysis, is actively used in research-oriented genetics
      clinics, with the transition to exomes as a standard procedure underway. This
      transition is challenging; identification of potentially causal mutation(s)
      amongst ~10(6) variants requires specialized computation in combination with
      expert assessment. This study analyzes the usability of user interfaces for
      clinical exome analysis software. There are two study objectives: (1) To
      ascertain the key features of successful user interfaces for clinical exome
      analysis software based on the perspective of expert clinical geneticists, (2) To
      assess user-system interactions in order to reveal strengths and weaknesses of
      existing software, inform future design, and accelerate the clinical uptake of
      exome analysis. METHODS: Surveys, interviews, and cognitive task analysis were
      performed for the assessment of two next-generation exome sequence analysis
      software packages. The subjects included ten clinical geneticists who interacted
      with the software packages using the "think aloud" method. Subjects' interactions
      with the software were recorded in their clinical office within an urban research
      and teaching hospital. All major user interface events (from the user
      interactions with the packages) were time-stamped and annotated with coding
      categories to identify usability issues in order to characterize desired features
      and deficiencies in the user experience. RESULTS: We detected 193 usability
      issues, the majority of which concern interface layout and navigation, and the
      resolution of reports. Our study highlights gaps in specific software features
      typical within exome analysis. The clinicians perform best when the flow of the
      system is structured into well-defined yet customizable layers for incorporation
      within the clinical workflow. The results highlight opportunities to dramatically
      accelerate clinician analysis and interpretation of patient genomic data.
      CONCLUSION: We present the first application of usability methods to evaluate
      software interfaces in the context of exome analysis. Our results highlight how
      the study of user responses can lead to identification of usability issues and
      challenges and reveal software reengineering opportunities for improving clinical
      next-generation sequencing analysis. While the evaluation focused on two
      distinctive software tools, the results are general and should inform active and
      future software development for genome analysis software. As large-scale genome
      analysis becomes increasingly common in healthcare, it is critical that efficient
      and effective software interfaces are provided to accelerate clinical adoption of
      the technology. Implications for improved design of such applications are
      discussed.

PMID- 24860972
TI  - Hypoxia inhibits JAK2V617F activation via suppression of SHP-2 function in
      myeloproliferative neoplasm cells.
AB  - The hypoxic microenvironment of the bone marrow, known as the hypoxic niche,
      supports hematopoietic stem cell quiescence and maintains long-term repopulation
      activity. Hypoxia also affects the expansion of progenitor cells and enhances
      erythropoiesis and megakaryopoiesis. In contrast to the known effects of hypoxia
      on normal hematopoiesis, the effects of the hypoxic environment of the bone
      marrow on the pathogenesis of myeloproliferative neoplasms (MPNs) have not been
      well studied. In the present study, we investigated the role of the hypoxic
      environment in the pathophysiology of MPNs, focusing on JAK2V617F, a major driver
      of mutation in Philadelphia-negative MPNs. We found that the activity of
      JAK2V617F was suppressed in hypoxic conditions not only in JAK2V617F-positive
      leukemia cells, but also in primary peripheral blood mononuclear cells from
      patients with polycythemia vera. Concomitant with the inhibition of JAK2V617F
      activity, hypoxia increased the expression of p27/KIP1, the primary negative
      regulator of the cell cycle, and inhibited cell cycle progression in JAK2V617F
      positive leukemia cell lines. The spontaneous erythroid colony formation of
      primary cells from polycythemia vera patients was also suppressed under hypoxic
      conditions. We also revealed that the hypoxia-induced overproduction of reactive
      oxygen species played a crucial role in the inhibition of JAK2V617F through the
      oxidation and inhibition of SHP-2, a protein tyrosine phosphatase that contains
      SH-2, which is required for JAK2 activation. In conclusion, a hypoxic environment
      may modulate JAK2-positive MPN cell fate and disease progression through the
      suppression of SHP-2 function and the subsequent suppression of JAK2V617F
      activity. 

PMID- 24860973
TI  - Implants failures related to endodontic treatment. An observational retrospective
      study.
AB  - OBJECTIVE: The aim of the study was to analyze potential etiological risk factors
      that constitute a complex problem in the clinical management of peri-implantitis.
      MATERIALS AND METHODS: An observational retrospective study was conducted to
      describe the possible effect of lesions of origin pulpar and/or periapical
      success or failure of the implant. The sample consisted of review of 800
      implants, of which 500 were conducted at the Faculty of Dentistry of the UANL and
      300 private clinics of Maxillofacial surgeons experienced in the placement of
      those who reside in Monterrey, Mexico. Five hundred and eighty cases correspond
      to female patients while that 220 patients of the male gender. The age of
      patients at the time of placing the implant ranged from 28 to 81 years. RESULTS:
      Of 800 study subjects who underwent dental implant treatments, 200 cases (25%)
      were detected which presented endodontic failure prior and/or adjacent to the
      placement of the implant. The 50.41% had peri-implantitis, recording 62 cases in
      the Faculty and 18 cases (23.38%) in private clinics, finding that there was a
      statistically significant difference between the presence and absence of peri
      implantitis in terms of failed endodontic prior and/or adjacent to the placement
      of the implant. CONCLUSIONS: Within the limitations of this observational
      retrospective study, it could be concluded that the development of inflammatory
      changes mediated by the presence of remnant bacteria surrounding hard tissues
      adjacent to implants might induce late failures of implants, and potentially
      trigger pathological features of apical peri-implantitis.

PMID- 24860974
TI  - Three-dimensional ultrasound in obstetrics practice: myth or reality?

PMID- 24860975
TI  - [Climacteric syndrome in a Northeastern Brazilian city: a household survey].
AB  - PURPOSE: To assess the prevalence of Climacteric Syndrome (CS) in women from a
      municipality of Northeastern Brazil which is less developed socioeconomically.
      METHODS: A prospective household survey was performed in Sao Luis, Maranhao,
      Brazil with 1,210 climacteric women aged 45 to 60 years. Interviews were applied
      using previously tested standard questionnaires from April to July 2008. The
      severity of climacteric symptoms was analyzed by circulatory and psychological
      indexes and the latter were associated with menopausal status. Multiple
      correspondence analysis was used to assess the relation among climacteric
      symptoms. RESULTS: Most patients were 55 to 60 years old (35.3%), mulatto
      (37.9%), with 9-11 years of schooling (39.8%), with a partner (56%), Catholic
      (73.9%) and belonged to the socioeconomic class C (51.1%). The prevalence of CS
      was 85.9%, and hot flashes (56.4%) and sweating (50.4%) were the most prevalent
      symptoms. The most frequent psychological symptoms were nervousness (45%) and
      emotional liability (44.8%). The severity of vasomotor and psychological symptoms
      was significantly higher during the peri and postmenopausal period (p<0.05).
      Vaginal dryness (62.7%) was the most prevalent urogenital complaint. CONCLUSION:
      The prevalence of CS was high among women from Sao Luis, Maranhao, Brazil.

PMID- 24860976
TI  - [Total body and trunk fat mass and the gait performance in postmenopausal women].
AB  - PURPOSE: To determine the relationship between total body and trunk fat mass and
      gait performance in postmenopausal women. METHODS: Thirty-nine postmenopausal
      women aged 50 years or more were studied. The following items were determined:
      weight and height to calculate body mass index (BMI), body composition using the
      technique of Dual-Energy X-ray Absorptiometry (DXA), and gait using
      baropodometry. The body composition variables used were total body fat, percent
      body fat and trunk fat, while the gait variables were percent double stance time
      and single stance time and gait speed. The women were divided into two groups
      according to the median for each body composition variable: less and more body
      fat, less and more percent body fat and less and more trunk fat. To compare the
      gait variables between groups, we used the Mann-Whitney test. To evaluate the
      possible relationships between body composition variables and gait variables, we
      used the Spearman correlation test. All analyses were performed with the level of
      significance set at 5%. RESULTS: The group with more trunk fat showed longer
      double stance time (p=0.007) and lower values of single stance time (0.033) than
      the group with less trunk fat. We found significant and positive correlations
      between trunk fat and double stance time (R=0.40) and negative correlations
      between trunk fat and single stance time (R=-0.32). CONCLUSION: Postmenopausal
      women with a greater amount of trunk fat tended to have impaired gait
      performance.

PMID- 24860977
TI  - [Impact of training about cervical cancer screening on health professionals
      working in basic health care units].
AB  - PURPOSE: To evaluate the impact of training professionals involved in the
      screening for cervical cancer in Basic Health Units in the city of Goiania (GO).
      METHODS: This was and intervention study in which the following data contained in
      the cervical cytopathology test form were examined: the woman's personal data,
      anamnesis, clinical examination and identification of the professional
      responsible for the collection. Professional training was evaluated by comparing
      the forms referring to the period from January 2007 to April 2009, before
      training, with the forms referring to the period from July 2010 to December 2012,
      after training. The Pearson chi2 test was used to analyze the results of
      training, with the 5% level of significance. RESULTS: After training, there was a
      significantly increased frequency of recording patient schooling (from 67.2 to
      92.6%, p<0.001), telephone number (from 78.9 to 98.7%, p<0.001), cervical
      inspection (from 86.8 to 96.6%, p<0.001), and signs suggestive of sexually
      transmitted diseases (from 80.8 to 93.5%, p<0.001). There was a reduction in the
      frequency of performing the exam within an interval of less than one year
      (p<0.001) and of one year (p<0.001). There was a reduction in the frequency of
      Pap smear testing in women under 25 years of age, from 22.0 to 17.9% (p<0.001).
      There was a significant increase in the proportion of satisfactory samples from
      70.4 to 80.2% (p<0.001). A reduction of confounding factors was observed. The
      desiccation frequency was 2.9% before training and 2.0% after training (p<0.001).
      There was an increase in the frequency of representation of endocervical cells
      from 79.5 to 88.5% (p<0.001). CONCLUSION: After training, there was a significant
      improvement in completing the application form, the performance of such tests
      regarding frequency and the age range recommended by the Ministry of Health, and
      the adequacy of the sample.

PMID- 24860978
TI  - Copper-catalyzed aerobic oxidative N-S bond functionalization for C-S bond
      formation: regio- and stereoselective synthesis of sulfones and thioethers.
AB  - A regio- and stereoselective synthesis of sulfones and thioethers by means of
      Cu(I)-catalyzed aerobic oxidative N-S bond cleavage of sulfonyl hydrazides,
      followed by cross-coupling reactions with alkenes and aromatic compounds to form
      the C sp 2-S bond, is described herein. N2 and H2O are the byproducts of this
      transformation, thus offering an environmentally benign process with a wide range
      of potential applications in organic synthesis and medicinal chemistry.

PMID- 24860979
TI  - Distortion of a hybrid stent graft following a frozen elephant trunk procedure.
AB  - We describe a case of an acute type A dissection, where technical problems during
      the frozen elephant trunk technique led to a distortion of the hybrid stent graft
      with severe stenosis of the thoracic aortic endoprosthesis. Interventional
      aortoplasty was performed to re-establish flow. This new technique bears some
      risk of technical failure and therefore should be applied only after careful
      considerations.

PMID- 24860981
TI  - Platform switching minimises crestal bone loss around dental implants: truth or
      myth?
AB  - The aim was to assess the role of platform switching (PS) in minimising crestal
      bone loss around dental implants through a systematic review of the currently
      available clinical evidence. To address the focused question 'Does PS minimise
      crestal bone loss compared with non-platform-switched (NPS) implants?',
      PubMed/Medline and Google Scholar databases were explored from 1986 up to and
      including December 2013 using the following key words in different combinations:
      'bone loss', 'dental implant', 'diameter', 'mandible', 'maxilla' and 'platform
      switching'. Letters to the Editor, unpublished data, historical reviews, case
      reports and articles published in languages other than English were excluded.
      Fifteen clinical studies were included. In seven studies, PS and NPS implants
      were placed in both the maxilla and mandible. In 13 studies, implants were placed
      at crestal bone levels whereas in one study, implants were placed supracrestally.
      Three studies reported the bucco-lingual (or transversal) width of the alveolar
      ridge which ranged between 7-8 mm. Seven studies reported that implants placed
      according to the PS concept did not minimise crestal bone loss as compared with
      NPS implants. 3D-Implant positioning, width of alveolar ridge and control of
      micromotion at the implant-abutment interface are the more critical factors that
      influence crestal bone levels than PS.

PMID- 24860980
TI  - Reductions of the components of the calreticulin/calnexin quality-control system
      by proteasome inhibitors and their relevance in a rodent model of Parkinson's
      disease.
AB  - Evidence indicates that the ubiquitin-proteasome system and the endoplasmic
      retculum (ER) quality-control system work in concert to ensure that proteins are
      correctly folded in the ER and that misfolded proteins are retrotransported to
      the cytosol for degradation by proteasomes. Dysfunction of either system results
      in developmental abnormalities and even death in animals. This study investigates
      whether and how proteasome inhibition impacts the components of the calreticulin
      (CRT)/calnexin (CNX) glycoprotein folding machinery, a typical ER protein quality
      control system, in the context of early neuronal injury. Here we report that
      proteasome inhibitor treatments, at nonlethal levels, reduced protein levels of
      CRT and ERp57 but not of CNX. These treatments increased protein levels of CRT in
      culture media, an effect blocked by brefeldin A, an inhibitor of protein
      trafficking; by contrast, ERp57 was not detected in culture media. Knockdown of
      CRT levels alone increased the vulnerability of SH-SY5Y, a neuronal cell line, to
      6-hydroxydopamine (6-OHDA) toxicity. In a rat model of Parkinson's disease,
      intrastriatal 6-OHDA lesions resulted in decreased levels of CRT and ERp57 in the
      midbrain. These findings suggest that reduction of the components of CRT/CNX
      glycoprotein quality-control system may play a role in neuronal injury in
      Parkinson's disease and other neurodegenerative disorders associated with
      dysfunction of the ubiquitin-proteasome system.

PMID- 24860982
TI  - Matrine reduces yeast-to-hypha transition and resistance of a fluconazole
      resistant strain of Candida albicans.
AB  - AIMS: To evaluate the potential effect of matrine on reducing the growth of hypha
      and lowering the resistance of a fluconazole-resistant colony of Candida
      albicans. METHODS AND RESULTS: Candida albicans SC5314 and a fluconazole
      resistant C. albicans 215 were used. As for C. albicans SC5314, minimal
      inhibitory concentration (MIC(80)) and effective concentration (EC(50)) were
      determined, 1 mg ml(-1) matrine could inhibit nearly 80% of planktonic growth by
      inverted microscope, 2 mg ml(-1) matrine suppressed 50% of metabolic activity of
      biofilm by XTT assay, vanishing hypha could be observed on spider agar containing
      2 mg ml(-1) matrine, the expressions of three hypha-related genes, namely ALS 3,
      SUN 41 and PBS 2, were suppressed by 29, 45 and 61% by 2 mg ml(-1) matrine. Also,
      matrine could lower the resistance of C. albicans 215, in either the free
      floating form or the biofilm phenotype. CONCLUSIONS: Matrine had favourable
      antifungal potential and might be able to reverse the fluconazole resistance of
      clinical isolates at relatively high concentration. The anti-candidal performance
      of matrine could be tightly associated with yeast-to-hypha transition proved by
      spider agar test and qRT-PCR. SIGNIFICANCE AND IMPACT OF STUDY: More efforts are
      needed to find new antifungal agents. Matrine could be a potential candidate to
      fight against Candida-related infections by regulating yeast-to-hypha transition.

PMID- 24860984
TI  - Diazepinoporphyrazines containing peripheral styryl substituents and their
      promising nanomolar photodynamic activity against oral cancer cells in liposomal
      formulations.
AB  - The photochemical properties and photodynamic activity of three porphyrazines
      (Pzs) containing annulated diazepine rings, including novel demetalated
      porphyrazine-possessing bis(styryl)diazepine moieties were investigated. The
      porphyrazines were evaluated in terms of their electronic absorption and emission
      properties, their tendency to undergo aggregation and photodegradation, as well
      as their singlet oxygen generation efficiency. The in vitro photodynamic activity
      of the porphyrazines and their liposomal formulations were examined by using two
      oral squamous cell carcinoma cell lines. Magnesium(II)
      tribenzodiazepinoporphyrazine (1) revealed the highest phototoxic effect in both
      cell lines used, H413 and HSC-3. Encapsulation of Pz 1 into L-alpha-phosphatidyl
      D,L-glycerol:1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine liposomes resulted
      in a nearly threefold increase in photocytotoxicity relative to that of the
      solution of Pz 1 (IC50 values of 45 and 129 nM, respectively).

PMID- 24860983
TI  - Muscle lim protein isoform negatively regulates striated muscle actin dynamics
      and differentiation.
AB  - Muscle lim protein (MLP) has emerged as a critical regulator of striated muscle
      physiology and pathophysiology. Mutations in cysteine and glycine-rich protein 3
      (CSRP3), the gene encoding MLP, have been directly associated with human
      cardiomyopathies, whereas aberrant expression patterns are reported in human
      cardiac and skeletal muscle diseases. Increasing evidence suggests that MLP has
      an important role in both myogenic differentiation and myocyte cytoarchitecture,
      although the full spectrum of its intracellular roles has not been delineated. We
      report the discovery of an alternative splice variant of MLP, designated as MLP
      b, showing distinct expression in neuromuscular disease and direct roles in actin
      dynamics and muscle differentiation. This novel isoform originates by alternative
      splicing of exons 3 and 4. At the protein level, it contains the N-terminus first
      half LIM domain of MLP and a unique sequence of 22 amino acids. Physiologically,
      it is expressed during early differentiation, whereas its overexpression reduces
      C2C12 differentiation and myotube formation. This may be mediated through its
      inhibition of MLP/cofilin-2-mediated F-actin dynamics. In differentiated striated
      muscles, MLP-b localizes to the sarcomeres and binds directly to Z-disc
      components, including alpha-actinin, T-cap and MLP. The findings of the present
      study unveil a novel player in muscle physiology and pathophysiology that is
      implicated in myogenesis as a negative regulator of myotube formation, as well as
      in differentiated striated muscles as a contributor to sarcomeric integrity.

PMID- 24860986
TI  - Growth and differentiation of a long bone in limb development, repair and
      regeneration.
AB  - Repair from traumatic bone fracture is a complex process that includes mechanisms
      of bone development and bone homeostasis. Thus, elucidation of the
      cellular/molecular basis of bone formation in skeletal development would provide
      valuable information on fracture repair and would lead to successful skeletal
      regeneration after limb amputation, which never occurs in mammals. Elucidation of
      the basis of epimorphic limb regeneration in amphibians would also provide
      insights into skeletal regeneration in mammals, since the epimorphic regeneration
      enables an amputated limb to re-develop the three-dimensional structure of bones.
      In the processes of bone development, repair and regeneration, growth of the bone
      is achieved through several events including not only cell proliferation but also
      aggregation of mesenchymal cells, enlargement of cells, deposition and
      accumulation of extracellular matrix, and bone remodeling. 

PMID- 24860985
TI  - Current diagnostic and management options in perihilar cholangiocarcinoma.
AB  - Cholangiocarcinomas (CCAs) are heterogeneous biliary tract tumors with dismal
      prognosis. Perihilar CCA (pCCA) involves the large bile ducts of the hepatic
      hilum, and is the most common type of CCA. Primary sclerosing cholangitis (PSC)
      is an established risk factor for pCCA. Although the diagnosis of pCCA is
      challenging, recent advances have been made including cytologic techniques such
      as fluorescence in situ hybridization. Endoscopic ultrasound with sampling of
      regional lymph nodes is emerging as a valuable diagnostic modality in the
      diagnosis and staging of pCCA. Curative treatment options are limited to early
      stage disease, and include surgical resection and liver transplantation after
      neoadjuvant therapy. This underscores the importance of early detection, and the
      need for development of innovative diagnostic tools such as biomarkers. A dense
      desmoplastic tumor stroma plays an integral role in pCCA progression. The tumor
      stroma represents an additional target for development of new therapies. Herein,
      we discuss these advances in the diagnosis and treatment of pCCA.

PMID- 24860987
TI  - Routine noninvasive prenatal screening for fetal RHD in plasma of RhD-negative
      pregnant women-2 years of screening experience from Denmark.
AB  - OBJECTIVE: Prenatal and postnatal RhD prophylaxis reduces the risk of RhD
      immunization in pregnancies of RhD-negative women. Based on the result from
      prenatal screening for the fetal RHD gene, prenatal RhD prophylaxis in Denmark is
      targeted to RhD-negative women who carry an RhD-positive fetus. Here, we present
      a 2-year evaluation of a nationwide prenatal RHD screening. METHODS: Blood
      samples were drawn from RhD-negative women in gestational week 25. DNA was
      extracted from maternal plasma and analyzed for the RHD gene. The prenatal RHD
      results were compared with the serological typing of newborns in 12,668
      pregnancies. Early compliance was assessed for 690 pregnancies. RESULTS: The
      sensitivity for the detection of fetal RHD was 99.9% (95% CI: 99.7-99.9%).
      Unnecessary recommendation of prenatal RhD prophylaxis was avoided in 97.3% of
      the women carrying an RhD-negative fetus. Fetuses that were seropositive for RhD
      were not detected in 11 pregnancies (0.087%). The sample uptake percentage was
      84.2%, and the compliance for prenatal anti-D administration was 93.2%.
      CONCLUSION: The high sensitivity, maintained over 2 years, underlines the
      reliability of routine prenatal fetal RHD screening in RhD-negative pregnant
      women, specifically at 25 weeks of gestation. The remaining challenges are
      logistical and are related to program compliance.

PMID- 24860989
TI  - Sox7 in vascular development: review, insights and potential mechanisms.
AB  - Cardiovascular development is crucial to the survival of higher organisms,
      integrally transporting oxygen and nutrients and in later life, facilitating
      immune function. Only in recent years has the molecular basis of the formation of
      this ancient conduit system been explored. While transcription factors are
      essential to specify and differentiate core cellular and structural components of
      the developing heart and vessels, only a subset of these essential factors are
      currently known. A transcription factor of emerging importance in the
      cardiovascular system is Sox7, a member of the F group of Sox genes, as Sox7
      removal in recent animal and cellular studies has resulted in disruptions of
      cardiovascular development. However, the molecular mechanisms of Sox7 action have
      largely remained obscure. In this paper, we first review the highly conserved and
      robust cardiovascular expression pattern of Sox7 across multiple species. We then
      provide evidence of a compelling role for Sox7 in vascular development,
      elucidating major pathways in which Sox7 functions, including VEGF/Flk1
      signaling, Wnt signaling, and Notch pathway. Furthermore, we propose mechanisms
      connecting all of these important developmental pathways through Sox7, in a way
      not previously postulated in the developing vascular system. The emerging picture
      reveals Sox7 as an important developmental gene that connects other vascular
      regulators and that has significance in human disease. 

PMID- 24860988
TI  - [Radiobiology of ablative dose in stereotactic irradiation: data update].
AB  - Stereotactic radiotherapy is a radiation technique, which is becoming more and
      more available and applicable for physicians. A good efficacy and safety are
      observed in clinical practice. However, the radiobiology of ablative radiation is
      still under question. The radiobiological principles of the 5R have to be
      discussed. The roles of hypoxia and vascularization, more specifically,
      angiogenesis and vasculogenesis seem to be dominating. 

PMID- 24860990
TI  - Mechanisms of cranial placode assembly.
AB  - Cranial placodes are transient ectodermal structures contributing to the paired
      sensory organs and ganglia of the vertebrate head. Placode progenitors are
      initially spread and intermixed within a continuous embryonic territory
      surrounding the anterior neural plate, the so-called pan-placodal region, which
      progressively breaks into distinct and compact placodal structures. The
      mechanisms driving the formation of these discrete placodes from the initial
      scattered distribution of their progenitors are poorly understood, and the
      implication of cell fate changes, local sorting out or massive cell movements is
      still a matter of debate. Here, we discuss different models that could account
      for placode assembly and review recent studies unraveling novel cellular and
      molecular aspects of this key event in the construction of the vertebrate head. 

PMID- 24860991
TI  - Generation of pluripotent stem cells via protein transduction.
AB  - The development of techniques for reprogramming somatic cells led to the birth of
      the cloned sheep ?Dolly? and the generation of induced pluripotent stem cells
      (iPSCs). iPSCs hold great promise for in vitro disease modeling, new drug
      screening, regenerative medicine and agricultural production. These cells can
      differentiate into almost any tissue types and they can be used to produce
      autografts that will not be rejected by the patient. However, practical
      application has been limited by the potential for insertion mutagenesis and by
      the complexity of the associated procedures. A protein-based approach to
      generation of iPSCs could offer better prospects by avoiding these problems. This
      review provides an overview of the key processes and mechanism involved in
      protein-based somatic cell reprogramming, discusses some promising methods for
      increasing its efficiency and future challenges. 

PMID- 24860992
TI  - Zygotic expression of Exostosin1 (Ext1) is required for BMP signaling and
      establishment of dorsal-ventral pattern in Xenopus.
AB  - Exostosin 1 (EXT1) is a glycosyltransferase that contributes to the biosynthesis
      of heparan sulfate proteoglycans (HSPG). Loss of ext1 function leads to the human
      genetic disorder hereditary multiple exostoses (HME) and inhibits development in
      mouse, zebrafish and Drosophila. In Xenopus, loss of maternal EXT1 leads to
      impaired wnt11 signaling, resulting in a loss of dorsal embryonic development
      (Tao et al., 2005), but the functions of zygotic ext1 have not been elucidated.
      In this study, morpholino oligonucleotides were used to generate a zygotic
      partial loss of function for ext1, in order to evaluate the requirements for ext1
      function in gastrulation and paracrine signaling. Transcriptional profiling was
      carried out by microarray. Validation and subsequent analyses of gene expression
      were performed using Q-RT-PCR and in situ hybridization. Western blots were used
      to assess paracrine signaling pathway activity. Introduction of ext1 MO led to
      gastrulation defects, which were partially rescued by co-injection of ext1 mRNA.
      Microarray-based comparisons of gene expression in control vs. Ext1 MO embryos
      identified several developmentally significant genes that are dependent upon Ext1
      function, including brachyury (Xbra). In addition, decreased Ext1 was shown to
      reduce the level of Wnt8 and BMP4 signaling and disrupt ventral-specific gene
      expression. Ext1 function is required for maintenance of normal levels of BMP and
      wnt, as well as their target genes. In addition, expression of xbra and the
      establishment of ventral mesoderm depend upon normal levels of Ext1. These
      findings suggest that ext1-dependent synthesis of HSPG is critical for wnt and
      BMP signaling, mesodermal identity, and ventral pattern. 

PMID- 24860993
TI  - Focal adhesion kinase as a mechanotransducer during rapid brain growth of the
      chick embryo.
AB  - Expansion of the hollow fluid-filled embryonic brain occurs by an increase in
      intraluminal pressure created by accumulation of cerebrospinal fluid (CSF).
      Experiments have shown a direct correlation between cavity pressure and cell
      proliferation within the neuroepithelium. These findings lead us to ask how
      mechanistically this might come about. Are there perhaps molecules on the luminal
      surface of the embryonic neuroepithelium, such as focal adhesion kinases (FAKs)
      known to respond to tension in other epithelial cells? Immunodetection using
      antibodies to total FAK and p-FAK was performed with subsequent confocal analysis
      of the pattern of their activation under normal intraluminal pressure and induced
      chronic pressure. Western analysis was also done to look at the amount of FAK
      expression, as well as its activation under these same conditions. Using
      immunolocalization, we have shown that FAK is present and activated on both
      apical and basolateral surfaces and within the cytoplasm of the neuroepithelial
      cells. This pattern changed profoundly when the neuroepithelium was under
      pressure. By Western blot, we have shown that FAK was upregulated and activated
      in the neuroepithelium of the embryos just after the neural tube becomes a closed
      pressurized system, with phosphorylation detected on the luminal instead of the
      basal surface, along with an increase in cell proliferation. Chronic hyper
      pressure does not induce an increase in phosphorylation of FAK. In conclusion,
      here we show that neuroepithelial cells respond to intraluminal pressure via FAK
      phosphorylation on the luminal surface. 

PMID- 24860994
TI  - Expression pattern of zcchc24 during early Xenopus development.
AB  - We report the expression pattern of a novel Xenopus laevis gene, zcchc24, which
      encodes a protein containing two zinc finger domains from the zf-CCHC and zf
      3CxxC superfamilies. This protein shares >84% amino acid identity with its
      vertebrate homologues. During X. laevis embryonic development, zcchc24 is
      expressed at gastrula stages in the dorsal mesoderm, including the cardiac
      precursors region. During neurula stages, zcchc24 is expressed as two stripes in
      the dorsal region, more precisely, in the somitogenic mesoderm until the cardiac
      mesoderm. At early tailbud stages, zcchc24 continues to be expressed in these
      regions, but starts to be expressed in the migrating neural crest. Later, this
      gene is expressed in the head, branchial arches, heart and somites. The zinc
      finger domains present in Zcchc24 protein and its dynamic gene expression pattern
      suggest that Zcchc24 might be involved in the regulation of heart, somites and of
      branchial arch formation/patterning, namely in the regulation of apoptosis. 

PMID- 24860995
TI  - Xenopus cadherin 5 is specifically expressed in endothelial cells of the
      developing vascular system.
AB  - Vasculogenesis is an important, multistep process leading to the formation of a
      functional primary network of blood vessels in the developing embryo. A series of
      interactions between secreted growth factors and their specific receptors leads
      to the specification of mesodermal cells to become hemangioblasts, which then
      differentiate into angioblasts. These subsequently proliferate, coalesce into
      cords and finally form tubular vascular structures. For proper function of these
      primary blood vessels, the close connection of endothelial cells is required.
      This is conferred by the interaction of an endothelium specific cadherin
      (Cadherin-5), starting during early vascular development. However, this
      interaction remains important throughout life and ageing. Therefore, cadherin-5
      is a useful marker for late stages of vasculogenesis in several vertebrate
      species. To establish cadherin-5 as a marker for vascular studies in Xenopus, we
      cloned the Xenopus laevis ortholog and analyzed its expression pattern during
      embryogenesis. 

PMID- 24860996
TI  - Developmental expression of chicken FOXN1 and putative target genes during
      feather development.
AB  - FOXN1 is a member of the forkhead box family of transcription factors. FOXN1 is
      crucial for hair outgrowth and thymus differentiation in mammals. Unlike the
      thymus, which is found in all amniotes, hair is an epidermal appendage that arose
      after the last shared common ancestor between mammals and birds, and hair and
      feathers differ markedly in their differentiation and gene expression. Here, we
      show that FOXN1 is expressed in embryonic chicken feathers, nails and thymus,
      demonstrating an evolutionary conservation that goes beyond obvious homology. At
      embryonic day (ED) 12, FOXN1 is expressed in some feather buds and at ED13
      expression extends along the length of the feather filament. At ED14 FOXN1 mRNA
      is restricted to the proximal feather filament and is not detectable in distal
      feather shafts. At the base of the feather, FOXN1 is expressed in the epithelium
      of the feather sheath and distal barb and marginal plate, whereas in the
      midsection FOXN1 transcripts are mainly detected in the barb plates of the
      feather filament. FOXN1 is also expressed in claws; however, no expression was
      detected in skin or scales. Despite expression of FOXN1 in developing feathers,
      examination of chick homologs of five putative mammalian FOXN1 target genes shows
      that, while these genes are expressed in feathers, there is little similarity to
      the FOXN1 expression pattern, suggesting that some gene regulatory networks may
      have diverged during evolution of epidermal appendages. 

PMID- 24860997
TI  - Multiple Dlk1 splice variants are expressed during early mouse embryogenesis.
AB  - Delta-like homologue 1 (Dlk1), an atypical Notch ligand, is known to have roles
      in growth and development, stem cell maintenance, and cancer. Evidence suggests
      that Dlk1 expression patterns are more complex than previously appreciated, with
      multiple isoforms expressed in various tissues in both the embryo and adult.
      However, the early embryonic expression of Dlk1 has not been well examined. Given
      that tissue specific Dlk1 knockouts have to date failed to recapitulate
      phenotypes associated with the conventional Dlk1 loss of function model, a better
      understanding of early Dlk1 expression is important. To address this question, we
      have examined Dlk1 expression during the early stages of mouse embryogenesis.
      Dlk1 expression was first detected at Theiler Stage 14 (TS14), and its expression
      pattern persisted in specific tissues through TS20. Further, we found that all
      known Dlk1 splice isoforms were expressed in early embryogenesis, with Dlk1-A and
      Dlk1-C/C2 isoforms being expressed at the highest levels. The broad co-expression
      of multiple Dlk1 isoforms corroborates recent work suggesting that Dlk1-mediated
      signaling may act through multiple DLK1 isoforms to balance differentiation. 

PMID- 24860998
TI  - Additional sex combs-like family genes are required for normal cardiovascular
      development.
AB  - Congenital heart disease (CHD) is the most common birth defect. However, the
      majority of CHD cases have unknown etiology. Here we report the identification of
      ASXL2 and ASXL1, two homologous chromatin factors, as novel regulators of heart
      development. Asxl2(-/-) fetuses have reduced body weight and display congenital
      heart malformations including thickened compact myocardium in the left ventricle,
      membranous ventricular septal defect, and atrioventricular valval stenosis.
      Although most Asxl2(-/-) animals survive to term, the neonates have patent ductus
      arteriosus and consequent lung hemorrhage and die soon after birth. Asxl1(-/-)
      fetuses have reduced body weight and display cleft palate, anophthalmia as well
      as ventricular septal defects and a failure in lung maturation. From these
      results, we conclude that normal heart development requires both ASXL proteins.
      In particular, ASXL2 plays an important role in heart morphogenesis and the
      transition from fetal to postnatal circulation.

PMID- 24860999
TI  - Accumulation and toxicity of CuO and ZnO nanoparticles through waterborne and
      dietary exposure of goldfish (Carassius auratus).
AB  - Dietary and waterborne exposure to copper oxide (CuO) and zinc oxide (ZnO)
      nanoparticles (NPs) was conducted using a simplified model of an aquatic food
      chain consisting of zooplankton (Artemia salina) and goldfish (Carassius auratus)
      to determine bioaccumulation, toxic effects, and particle transport through
      trophic levels. Artemia contaminated with NPs were used as food in dietary
      exposure. Fish were exposed to suspensions of the NPs in waterborne exposure. ICP
      MS analysis showed that accumulation primarily occurred in the intestine,
      followed by the gills and liver. Dietary uptake was lower, but was found to be a
      potential pathway for transport of NPs to higher organisms. Waterborne exposure
      resulted in about a 10-fold higher accumulation in the intestine. The heart,
      brain, and muscle tissue had no significant Cu or Zn. However, concentrations in
      muscle increased with NP concentration, which was ascribed to bioaccumulation of
      Cu and Zn released from NPs. Free Cu concentration in the medium was always
      higher than that of Zn, indicating CuO NPs dissolved more readily. ZnO NPs were
      relatively benign, even in waterborne exposure (p >= 0.05). In contrast, CuO NPs
      were toxic. Malondialdehyde levels in the liver and gills increased substantially
      (p < 0.05). Despite lower Cu accumulation, the liver exhibited significant
      oxidative stress, which could be from chronic exposure to Cu ions.

PMID- 24861000
TI  - Migration of components from cork stoppers to food: challenges in determining
      inorganic elements in food simulants.
AB  - The inorganic elements potentially migrating from cork to a food simulant [a
      hydroalcoholic solution containing 12 and 20% (v/v) ethanol] have been determined
      by means of inductively coupled plasma (ICP) with atomic emission and mass
      spectrometric detection. The experimental instrumental conditions were evaluated
      in depth, taking into account spectroscopic and nonspectroscopic interference
      caused by the presence of ethanol and other components in the sample. We report
      concentrations ranging from 4 MUg kg(-1) for Cd to 28000 MUg kg(-1) for Al in the
      food simulant (concentrations given in kilograms of cork). The values found for
      Ba, Mn, Fe, Cu, and Zn have been compared with the guideline values stated in EU
      Regulation 10/2011. In all cases, cork met the general safety criteria applicable
      to food contact material. Finally, we have proposed water as an alternative to
      the hydroalcoholic solution to simplify quantification of the tested elements
      using ICP techniques. 

PMID- 24861001
TI  - Insertions in the OCL1 locus of Acinetobacter baumannii lead to shortened
      lipooligosaccharides.
AB  - Genomes of 82 Acinetobacter baumannii global clones 1 (GC1) and 2 (GC2) isolates
      were sequenced and different forms of the locus predicted to direct synthesis of
      the outer core (OC) of the lipooligosaccharide were identified. OCL1 was in all
      GC2 genomes, whereas GC1 isolates carried OCL1, OCL3 or a new locus, OCL5. Three
      mutants in which an insertion sequence (ISAba1 or ISAba23) interrupted OCL1 were
      identified. Isolates with OCL1 intact produced only lipooligosaccharide, while
      the mutants produced lipooligosaccharide of reduced molecular weight. Thus, the
      assignment of the OC locus as that responsible for the synthesis of the OC is
      correct. 

PMID- 24861002
TI  - Learning about prophages from Francois Jacob.

PMID- 24861003
TI  - Molecular modeling of the Plasmodium falciparum pre-mRNA splicing and nuclear
      export factor PfU52.
AB  - UAP56/SUB2 is a DExD/H-box RNA helicase that is critically involved in pre-mRNA
      splicing and mRNA nuclear export. This helicase is broadly conserved and
      essential in many eukaryotic lineages, including protozoan and metazoan
      parasites. Previous research suggests that helicases from parasites could be
      promising drug targets for treating parasitic diseases. Accordingly,
      characterizing the structure and function of these proteins is of interest for
      structure-based, de novo design of new lead compounds. Here, we used homology
      modeling to construct a three-dimensional structure of PfU52 (PMDB ID:
      PM0079288), the Plasmodium falciparum ortholog of UAP56/SUB2, and explored the
      detailed architecture of its functional sites. Comparative in silico analysis
      revealed that although PfU52 shared many physicochemical, structural and dynamic
      similarities with its human homolog, it also displayed some unique features that
      could be exploited for drug design. 

PMID- 24861004
TI  - Polyunsaturated fatty acids in emerging psychosis: a safer alternative?
AB  - AIM: A promising approach of indicated prevention in individuals at increased
      risk of psychosis was based on the finding of potential neuroprotective
      properties of omega-3 polyunsaturated fatty acids (PUFAs). Considering the rising
      interest in omega-3 PUFA supplementation as preventive treatment strategy in
      young people at risk of psychosis, the question of safety issues must be
      addressed. METHODS: For this systematic review, a literature search for studies
      on omega-3 PUFAs for emerging psychosis with a focus on the safety profile was
      undertaken. Because limited data are available, information regarding potential
      side effects of omega-3 PUFAs was additionally derived from currently available
      data in psychotic disorders at different stages of the illness. Furthermore,
      helpful evidence from somatic disorders and healthy controls was used. RESULTS:
      In terms of safety issues, evidence from the randomized controlled trial in ultra
      high-risk individuals and a variety of studies in schizophrenia patients strongly
      suggests that omega-3 PUFAs are safe and well tolerated even when used in
      relatively high doses. Most commonly occurring but clinically rarely significant
      are mild gastrointestinal symptoms; similarly, the slight risk of prolonged
      bleeding time has not been shown to be clinically relevant. Differential effects
      on metabolic parameters, most of which appear beneficial, have been reported.
      CONCLUSIONS: Taken together, one promising aspect of omega-3 PUFAs is that there
      seem to be no reports of relevant deleterious side effects in humans, even at
      high doses. The differential effects on lipid parameters and bleeding time are
      noteworthy and need further clarification.

PMID- 24861006
TI  - Role of cilia in normal pancreas function and in diseased states.
AB  - Primary cilia play an essential role in modulating signaling cascades that shape
      cellular responses to environmental cues to maintain proper tissue development.
      Mutations in primary cilium proteins have been linked to several rare
      developmental disorders, collectively known as ciliopathies. Together with other
      disorders associated with dysfunctional cilia/centrosomes, affected individuals
      have increased risk of developing metabolic syndrome, neurologic disorders, and
      diabetes. In pancreatic tissues, cilia are found exclusively in islet and ductal
      cells where they play an essential role in pancreatic tissue organization. Their
      absence or disorganization leads to pancreatic duct abnormalities, acinar cell
      loss, polarity defects, and dysregulated insulin secretion. Cilia in pancreatic
      tissues are hubs for cellular signaling. Many signaling components, such as Hh,
      Notch, and Wnt, localize to pancreatic primary cilia and are necessary for proper
      development of pancreatic epithelium and beta-cell morphogenesis. Receptors for
      neuroendocrine hormones, such as Somatostatin Receptor 3, also localize to the
      cilium and may play a more direct role in controlling insulin secretion due to
      somatostatin's inhibitory function. Finally, unique calcium signaling, which is
      at the heart of beta-cell function, also occurs in primary cilia. Whereas voltage
      gated calcium channels trigger insulin secretion and serve a variety of
      homeostatic functions in beta-cells, transient receptor potential channels
      regulate calcium levels within the cilium that may serve as a feedback mechanism,
      regulating insulin secretion. This review article summarizes our current
      understanding of the role of primary cilia in normal pancreas function and in the
      diseased state.

PMID- 24861007
TI  - Chronic contained rupture of an abdominal aortic aneurysm: an insidious
      eventuality causing vertebra destruction in Behcet's disease.

PMID- 24861005
TI  - The role of stereotactic radiotherapy in the treatment of oligometastases.
AB  - "Oligometastasis" describes a limited number of metastases arising typically from
      solid tumors whose behavior suggests an "intermediate" malignant state since it
      may potentially have a more favorable prognosis. Historically, selected patients
      with oligometastases often underwent surgical resection since anecdotal evidence
      suggested it could improve progression-free or overall survival. No prospective
      randomized trial evidence to date supports survival benefits from surgery. Short
      courses of highly focused, very high dose radiotherapy (stereotactic
      radiosurgery; stereotactic body radiotherapy) have emerged as a surgical
      surrogate to manage oligometastates. For solitary brain metastases, randomized
      study evidence supports stereotactic radiosurgery as part of their management
      because of overall survival benefits. Modeled after stereotactic radiosurgery,
      stereotactic body radiotherapy for extracranial metastases is becoming
      increasingly common given its efficacy and low toxicity, is an active area of
      clinical research, and is the subject of this review. 

PMID- 24861008
TI  - Pharmacokinetic changes of drugs in a rat model of liver cirrhosis induced by
      dimethylnitrosamine, alone and in combination with diabetes mellitus induced by
      streptozotocin.
AB  - Rats with liver cirrhosis induced by N-dimethylnitrosamine (LC) and rats with LC
      with diabetes mellitus induced by streptozotocin (LCD) have been developed as
      animal models for human liver cirrhosis and liver cirrhosis with diabetes
      mellitus, respectively. Changes in the pharmacokinetics of drugs (mainly non
      renal clearance, CLNR) in LC and LCD rats reported in the literature compared
      with respective control rats were reviewed. This review mainly explains the
      changes in the CLNRs of drugs (which are mainly metabolized via hepatic
      microsomal cytochrome P450s, CYPs) in LC and LCD rats, in terms of the changes in
      in vitro hepatic intrinsic clearance (CLint; mainly due to the changes in CYPs in
      the disease state), free (unbound) fraction of a drug in the plasma (fp) and
      hepatic blood flow rate (QH) depending on the hepatic excretion ratio of the
      drug. Generally, changes in the CLNRs of drugs in LC and LCD rats could be well
      explained by the above-mentioned three factors. The mechanism of urinary
      excretion of drugs (such as glomerular filtration or renal active secretion or
      reabsorption) in LC and LCD rats is also discussed. The pharmacokinetics of the
      drugs reported in the LC and LCD rats were scarce in humans. Thus, the present
      rat data should be extrapolated carefully to humans.

PMID- 24861009
TI  - Observation and photophysical characterization of silicon phthalocyanine J
      aggregate dimers in aqueous solutions.
AB  - The use of macrocyclic molecules for both imaging and photodynamic therapy (PDT)
      has proven to be a powerful method for assessing and treating diseases,
      respectively. However, many potential candidates for these applications rely on
      rigid organic structures which are hydrophobic and thus lead to possible
      aggregation in aqueous solutions such as blood. Here, we describe the discovery
      of noncovalent J-aggregate dimers of the asymmetrically, axially modified silicon
      phthalocyanine 4 (Pc 4) in aqueous solutions through steady-state and time
      resolved spectroscopy. Remarkably, the monomer-dimer equilibrium is dictated by
      water content and pH, with free monomers resulting in favorable solvation
      conditions even after formation of the dimer complex. This work sheds light on
      previous observations of Pc 4 behavior in cells during PDT, and can further
      elucidate the structure-activity relationship of these important molecules. 

PMID- 24861010
TI  - Link N is cleaved by human annulus fibrosus cells generating a fragment with
      retained biological activity.
AB  - Presently, there are no established treatments to prevent, stop or even retard
      back pain arising from disc degeneration. Previous studies have shown that Link N
      can act as a growth factor and stimulate the synthesis of proteoglycans and
      collagens, in IVD. However, the sequences in Link N involved in modulating
      cellular activity are not well understood. To determine if disc cells can
      proteolytically process Link N, human disc cells were exposed to native Link N
      over a 48 h period and mass spectrometric analysis revealed that a peptide
      spanning residues 1-8 was generated in the presence of AF cells but not NP cells.
      Link N 1-8 significantly induced proteoglycan production in the presence of IL
      1beta NP and AF cells, confirming that the biological effect is maintained in the
      first 8 amino acids of the peptide and indicating that the effect is sustained in
      an inflammatory environment. Thus Link-N 1-8 could be a promising candidate for
      biologically induced disc repair, and the identification of such a stable
      specific peptide may facilitate the design of compounds to promote disc repair
      and provide alternatives to surgical intervention for early stage disc
      degeneration.

PMID- 24861012
TI  - Myco-synthesis of silver nanoparticles using Beauveria bassiana against dengue
      vector, Aedes aegypti (Diptera: Culicidae).
AB  - The efficacy of silver synthesized biolarvicide with the help of entomopathogenic
      fungus, Beauveria bassiana, was assessed against the different larval instars of
      dengue vector, Aedes aegypti. The silver nanoparticles were observed and
      characterized by a scanning electron microscope (SEM) and energy-dispersive X-ray
      (EDX). A surface plasmon resonance band was observed at 420 nm in UV-vis
      spectrophotometer. The characterization was confirmed by shape (spherical), size
      36.88-60.93 nm, and EDX spectral peak at 3 keV of silver nanoparticles. The
      synthesized silver nanoparticles have been tested against the different larval
      instars of Ae. aegypti at different concentrations for a period of 24 h. Ae.
      aegypti larvae were found more susceptible to the synthesized silver
      nanoparticles. The LC50 and LC90 values are 0.79 and 1.09 ppm with respect to the
      Ae. aegypti treated with B. bassiana (Bb) silver nanoparticles (AgNPs). First and
      second instar larvae of Ae. aegypti have shown cent percent mortality while third
      and fourth instars found 50.0, 56.6, 70.0, 80.0, and 86.6 and 52.4, 60.0, 68.5,
      76.0, and 83.3% mortality at 24 h of exposure in 0.06 and 1.00 ppm, respectively.
      It is suggested that the entomopathogenic fungus synthesized silver nanoparticles
      would be appropriate for environmentally safer and greener approach for new
      leeway in vector control strategy through a biological process.

PMID- 24861011
TI  - Biochemical and immunological characterization of annexin B30 from Clonorchis
      sinensis excretory/secretory products.
AB  - Clonorchis sinensis has been classified as group I biological carcinogen for
      cholangiocarcinoma by the World Health Organization. Biological studies on
      excretory/secretory products (ESPs) enabled us to understand the pathogenesis
      mechanism of C. sinensis and develop new strategies for the prevention of
      clonorchiasis. In this study, sequence analysis showed that annexin B30 from C.
      sinensis (CsANXB30) is composed of four annexin repeats which were characterized
      by type II and III Ca(2+)-binding sites or KGD motif with the capability of
      Ca(2+)-binding. In addition, immunoblot assay revealed that recombinant CsANXB30
      (rCsANXB30) could be recognized by the sera from rats infected with C. sinensis
      and the sera from rats immunized by CsESPs. Real-time PCR showed that its
      transcriptional level was the highest at the stage of metacercaria.
      Immunofluorescence assay was employed to confirm that CsANXB30 was distributed in
      the tegument, intestine, and egg of adult worms, as well as the tegument and
      vitellarium of metacercaria. rCsANXB30 was able to bind phospholipid in a Ca(2+)
      dependent manner and human plasminogen in a dose-dependent manner. Moreover,
      cytokine and antibody measurements indicated that rats subcutaneously immunized
      with rCsANXB30 developed a strong IL-10 production in spleen cells and a high
      level of IgG1 isotype, indicating that rCsANXB30 could trigger specific humoral
      and cellular immune response in rats. The present results implied that CsANXB30
      might be involved in a host-parasite interaction and affected the immune response
      of the host during C. sinensis infection. 

PMID- 24861014
TI  - Poly(exTTF): a novel redox-active polymer as active material for li-organic
      batteries.
AB  - The first polymer bearing exTTF units intended for the use in electrical charge
      storage is presented. The polymer undergoes a redox reaction involving two
      electrons at -0.20 V vs Fc/Fc(+) and is applied as active cathode material in a
      Li-organic battery. The received coin cells feature a theoretical capacity of 132
      mAh g(-1) , a cell potential of 3.5 V, and a lifetime exceeding more than 250
      cycles. 

PMID- 24861018
TI  - A concise and versatile synthesis of alkaloids from Kopsia tenuis: total
      synthesis of (+/-)-lundurine A and B.
AB  - A total synthesis of (+/-)-lundurines A and B is described. These natural
      products have a unique hexacyclic skeleton which includes a cyclopropane-fused
      indoline. A stereospecific construction of the pentasubstituted cyclopropane core
      was achieved, by radical cyclization using SmI2, with perfect stereoselectivity.
      Cyclizations to give seven- and five-membered heterocycles, under palladium and
      ruthenium catalysis, respectively, accomplished the total syntheses. The late
      stage construction of the F ring by ring-closing metathesis enabled access to the
      title compounds from a spiroindoline intermediate which is a common structure of
      other kopsia alkaloids.

PMID- 24861013
TI  - Statistical evaluation of a commercial Neospora caninum competitive ELISA in the
      absence of a gold standard: application to wild elk (Cervus elaphus) in Alberta.
AB  - Neospora caninum is an important abortive agent of domestic ruminants, but few
      diagnostic tools are available to reliably assess the exposure of wild cervid
      species such as elk (Cervus elaphus) to this pathogen, which limits our ability
      to understand their role in the life cycle of this parasite. In the absence of a
      gold standard test or panels of samples from individuals of known infection
      status, classical laboratory-based validation methods are not applicable.
      However, there are a number of statistical methods that can help in selecting an
      appropriate cut-off value and estimating the resulting diagnostic test
      performances. In this paper, the performance of a commercial competitive enzyme
      linked immunosorbent assay (cELISA) on elk serum samples was evaluated with two
      statistical approaches: a mixture distribution model fitted to the cELISA
      results, and a Bayesian latent class analysis combining results from the cELISA
      and an indirect immuno-fluorescence antibody test. Both methods indicated that
      the commercial kit could be used on elk serum with the specifications recommended
      by the manufacturer. In particular, the optimal combination of sensitivity and
      specificity were obtained for a percentage of inhibition cutoff of 30%. The 95%
      probability interval of the proportion of elk exposed to N. caninum, adjusting
      for the sensitivity and specificity of this test in elk, was estimated between
      1.3 and 7.4%. There was no association between the serological status of female
      elk and their pregnancy status. These results point out to the involvement of elk
      in a sylvatic cycle of N. caninum in this area.

PMID- 24861020
TI  - Reading instead of reasoning? Predictors of arithmetic skills in children with
      cochlear implants.
AB  - OBJECTIVES: The aim of the present study was to evaluate whether the arithmetic
      achievement of children with cochlear implants (CI) was lower or comparable to
      that of their normal hearing peers and to identify predictors of arithmetic
      achievement in children with CI. In particular we related the arithmetic
      achievement of children with CI to nonverbal IQ, reading skills and hearing
      variables. METHODS: 23 children with CI (onset of hearing loss in the first 24
      months, cochlear implantation in the first 60 months of life, atleast 3 years of
      hearing experience with the first CI) and 23 normal hearing peers matched by age,
      gender, and social background participated in this case control study. All
      attended grades two to four in primary schools. To assess their arithmetic
      achievement, all children completed the "Arithmetic Operations" part of the
      "Heidelberger Rechentest" (HRT), a German arithmetic test. To assess reading
      skills and nonverbal intelligence as potential predictors of arithmetic
      achievement, all children completed the "Salzburger Lesetest" (SLS), a German
      reading screening, and the Culture Fair Intelligence Test (CFIT), a nonverbal
      intelligence test. RESULTS: Children with CI did not differ significantly from
      hearing children in their arithmetic achievement. Correlation and regression
      analyses revealed that in children with CI, arithmetic achievement was
      significantly (positively) related to reading skills, but not to nonverbal IQ.
      Reading skills and nonverbal IQ were not related to each other. In normal hearing
      children, arithmetic achievement was significantly (positively) related to
      nonverbal IQ, but not to reading skills. Reading skills and nonverbal IQ were
      positively correlated. Hearing variables were not related to arithmetic
      achievement. CONCLUSIONS: Children with CI do not show lower performance in non
      verbal arithmetic tasks, compared to normal hearing peers.

PMID- 24861021
TI  - Antinociceptive effects of venlafaxine in a rat model of peripheral neuropathy:
      role of alpha2-adrenergic receptors.
AB  - This study was designed to determine whether acute or chronic venlafaxine
      administration was effective in alleviating symptoms of neuropathic pain in a rat
      model of neuropathic pain, and whether the effect of venlafaxine involved
      manipulation of alpha2-adrenoceptors,by determining the effect of yohimbine, a
      alpha2-adrenoceptor antagonist on its actions. Neuropathic pain was induced by
      chronic constriction injury (CCI) of the sciatic nerve in the rats that resulted
      in stimulus-evoked thermal hyperalgesia, tactile mechanical and cold allodynia.
      Acute venlafaxine injections (20 and 40 mg/kg i.p.) on the 7th, 14th and 21st
      postoperative days could not reduce tactile and cold hypersensitivity
      significantly compared to CCI group. But in these groups venlafaxine (40 mg/kg
      i.p.) blocked heat hyperalgesia. When venlafaxine (10 and 20mg/kg i.p.)
      administration was started on the first day after CCI and given daily until the
      14th day, tactile hypersensitivity and heat hyperalgesia considerably were
      attenuated. But when venlafaxine (20mg/kg i.p.) treatment was initiated on the
      10th day after CCI, once the model had been fully established, and given daily
      for 11 days, no differences in withdrawal thresholds were observed compared with
      CCI group however heat hyperalgesia significantly has been blocked. Also the
      effect of venlafaxine on heat hyperalgesia was reversed by pretreatment with
      yohimbine at all-time intervals. These results indicate that venlafaxine, when
      administered immediately after nerve injury, and for a sufficient period of time,
      can prevent the development and expression of neuropathic pain. Also we conclude
      that alpha2-adrenoceptors participate in the antinociceptive effects of
      venlafaxine.

PMID- 24861023
TI  - Ink-on-probe hydrodynamics in atomic force microscope deposition of liquid inks.
AB  - The controlled deposition of attolitre volumes of liquids may engender novel
      applications such as soft, nano-tailored cell-material interfaces, multi-plexed
      nano-arrays for high throughput screening of biomolecular interactions, and
      localized delivery of reagents to reactions confined at the nano-scale. Although
      the deposition of small organic molecules from an AFM tip, known as dip-pen
      nanolithography (DPN), is being continually refined, AFM deposition of liquid
      inks is not well understood, and is often fraught with inconsistent deposition
      rates. In this work, the variation in feature-size over long term printing
      experiments for four model inks of varying viscosity is examined. A hierarchy of
      recurring phenomena is uncovered and there are attributed to ink movement and
      reorganisation along the cantilever itself. Simple analytical approaches to model
      these effects, as well as a method to gauge the degree of ink loading using the
      cantilever resonance frequency, are described. In light of the conclusions, the
      various parameters which need to be controlled in order to achieve uniform
      printing are dicussed. This work has implications for the nanopatterning of
      viscous liquids and hydrogels, encompassing ink development, the design of probes
      and printing protocols. 

PMID- 24861022
TI  - Fisetin attenuates cerulein-induced acute pancreatitis through down regulation of
      JNK and NF-kappaB signaling pathways.
AB  - Acute pancreatitis (AP) is a complicated disease which is largely undiscovered.
      Fisetin, a natural flavonoid from fruits and vegetables, has been shown to have
      anti-inflammatory, antioxidant, and anti-cancer activities in various disease
      models. However, the effects of fisetin on AP have not been determined. Pre- and
      post- treatment of mice with fisetin reduced the severity of AP and pancreatitis
      associated lung injury and inhibited several biochemical parameters (pancreatic
      weight to body weight ratio, amylase, lipase, and myeloperoxidase activity) and
      production of inflammatory cytokines. In pancreatic acinar cells, fisetin also
      inhibited cell death and production of inflammatory cytokines. In addition,
      fisetin inhibited activation of c-Jun NH2-terminal kinase (JNK) and nuclear
      factor (NF)-kappaB in vivo and in vitro. In conclusion, these results suggest
      that fisetin exhibits anti-inflammatory effect on AP and could be a beneficial
      agent in the treatment of AP and its pulmonary complications. 

PMID- 24861024
TI  - Ultrahigh-resolution NMR spectroscopy.

PMID- 24861027
TI  - The influence of concentration on specific ion effects at the silica/water
      interface.
AB  - Second harmonic generation spectroscopy is a useful tool for monitoring changes
      in interfacial potential at buried insulator/liquid interfaces. Here we apply
      this technique to the silica/aqueous interface and monitor the changes in
      interfacial potential while varying the pH in the presence of different alkali
      halides at 0.1M concentration. Within the pH range explored, the bimodal
      distribution of acidic sites on planar silica is clearly observed, corresponding
      to two types of acidic SiOH groups. Comparing these data with previous work at
      0.5M sheds light on whether the presence of the ions stabilizes the charged or
      neutral state of the surface sites. For the alkali chlorides, with the exception
      of NaCl, we observe that the presence of the alkali chlorides stabilize the less
      acidic site in the protonated (SiOH) rather than deprotonated (SiO(-)) form. This
      unusual influence of the cation is attributed to the combination of interactions
      at the interface between water, surface sites and the electrolyte. Overall, we
      observe that the influence of the alkali ion on the ratio of the two types of
      sites and their effective acid dissociation constants is minor at 0.1M, unlike
      that observed at 0.5M. In contrast, the influence of the anion on the cooperative
      dissociation of surface sites and their relative distribution is little affected
      upon decreasing the concentration, which indicates that these specific anion
      effects are prevalent in nature. 

PMID- 24861026
TI  - NLRP3 inflammasome activation is required for fibrosis development in NAFLD.
AB  - NLR inflammasomes, caspase 1 activation platforms critical for processing key pro
      inflammatory cytokines, have been implicated in the development of nonalcoholic
      fatty liver disease (NAFLD). As the direct role of the NLRP3 inflammasome remains
      unclear, we tested effects of persistent NLRP3 activation as a contributor to
      NAFLD development and, in particular, as a modulator of progression from benign
      hepatic steatosis to steatohepatitis during diet-induced NAFLD. Gain of function
      tamoxifen-inducible Nlrp3 knock-in mice allowing for in vivo temporal control of
      NLRP3 activation and loss of function Nlrp3 knockout mice were placed on short
      term choline-deficient amino acid-defined (CDAA) diet, to induce isolated hepatic
      steatosis or long-term CDAA exposure, to induce severe steatohepatitis and
      fibrosis, respectively. Expression of NLRP3 associated proteins was assessed in
      liver biopsies of a well-characterized group of patients with the full spectrum
      of NAFLD. Nlrp3(-/-) mice were protected from long-term feeding CDAA-induced
      hepatomegaly, liver injury, and infiltration of activated macrophages. More
      importantly, Nlrp3(-/-) mice showed marked protection from CDAA-induced liver
      fibrosis. After 4 weeks on CDAA diet, wild-type (WT) animals showed isolated
      hepatic steatosis while Nlrp3 knock-in mice showed severe liver inflammation,
      with increased infiltration of activated macrophages and early signs of liver
      fibrosis. In the liver samples of patients with NAFLD, inflammasome components
      were significantly increased in those patients with nonalcoholic steatohepatitis
      (NASH) when compared to those with non-NASH NAFLD with mRNA levels of pro-IL1
      beta correlated to levels of COL1A1. Our study uncovers a crucial role for the
      NLRP3 inflammasome in the development of NAFLD. These findings may lead to novel
      therapeutic strategies aimed at halting the progression of hepatic steatosis to
      the more severe forms of this disease. Key message: Mice with NLRP3 inflammasome
      loss of function are protected from diet-induced steatohepatitis. NLRP3
      inflammasome gain of function leads to early and severe onset of diet-induced
      steatohepatitis in mice. Patients with severe NAFLD exhibit increased levels of
      NLRP3 inflammasome components and levels of pro-IL1beta mRNA correlate with the
      expression of COL1A1.

PMID- 24861028
TI  - Effect of home bleaching on the mechanical properties of resin luting cements
      using Hertzian indentation test.
AB  - AIM: The aim of the present study was to determine the effects of immersion time
      and 10% carbamide peroxide treatment using a Hertzian indentation test after
      placing resin-based cements into 37 degrees C distilled water, with and without
      10% carbamide peroxide. METHODS: Disc-shaped specimens (10-mm diameter * 1-mm
      thick), were prepared from five resin-based cements; seT PP, Maxcem Elite, RelyX
      Unicem, Panavia F, and G-Cem. The specimens of each material were randomly
      divided into three groups of six. The study groups were bleached with 10%
      carbamide peroxide on one surface for 21 days for 2 h per day. Two control groups
      were kept in distilled water for either 24 h or 21 days. A load was applied to
      the center of the disc using a hard, steel ball. The load at the first crack was
      recorded. RESULTS: Significant differences were observed between the cements. seT
      PP showed the highest strength, and G-Cem the lowest. Differences between the
      treatment and control groups were statistically significant for all cements,
      except Panavia F. CONCLUSIONS: The effect of 10% carbamide peroxide treatment
      reduces cement strength, which could be important for patients undergoing
      bleaching who have crowns.

PMID- 24861029
TI  - Women or LARC first? Reproductive autonomy and the promotion of long-acting
      reversible contraceptive methods.

PMID- 24861025
TI  - Therapeutic targeting of ERBB2 in breast cancer: understanding resistance in the
      laboratory and combating it in the clinic.
AB  - ERBB2 gene amplification occurs in about one quarter of breast carcinomas (BCs)
      and identifies a distinct clinical subset of BC. The introduction in the clinic
      of Trastuzumab, a humanized monoclonal antibody (mAb) directed to the ERBB2
      extracellular domain, has had a great impact on the therapeutic management of
      ERBB2+ BC. Yet, not all patients respond to Trastuzumab and resistance develops
      also among patients that initially benefit from Trastuzumab-based regimens. Pre
      clinical studies have discovered several mechanisms through which tumor cells may
      escape from Trastuzumab-mediated ERBB2 inhibition. These include rewiring of the
      ErbB signaling network, loss of ERBB2 expression, expression of ERBB2 isoforms
      refractory to Trastuzumab inhibition, vicarious signaling by non-ErbB tyrosine
      kinases and constitutive activation of downstream signaling routes, such as the
      PI3K pathway. While the relative contribution of each of these mechanisms to
      establishing Trastuzumab resistance in the clinical setting is not fully
      understood, much attention has been focused on abating resistance by achieving
      complete blockade of ERBB2-containing dimers. This approach, propelled by the
      development of novel anti-ERBB2 therapeutics, has led to the recent approval of
      Lapatinib, Pertuzumab and T-DM1 as additional anti-ERBB2 therapeutics in BC.
      However, full success is far from being achieved and resistance to ERBB2
      targeting remains a relevant problem in the clinical management of BC. Herein, we
      provide an overview of biological and molecular bases underpinning resistance to
      ERBB2 therapeutics in BC, discuss outstanding issues in the field of ERBB2
      therapeutic targeting and elaborate on future directions of translational
      research on ERBB2+ breast cancer. 

PMID- 24861030
TI  - Using confocal Raman microscopy to real-time monitor poplar cell wall swelling
      and dissolution during ionic liquid pretreatment.
AB  - The ionic liquids (ILs) are recognized as the potential solvents for the
      pretreatment of lignocellulosic materials before biomass conversion. However,
      little knowledge of how the cell wall of biomass responds to the IL locally and
      dynamically during the pretreatment is available. In the current work, the
      process of IL pretreatment of poplar using 1-ethyl-3-methylimidazolium acetate
      ([C2 mim][OAc]) was real-time monitored on a cellular level by employing confocal
      Raman microscopy. The results showed that the biomass dissolution during the IL
      pretreatment can be clearly divided into two stages: (1) slow penetration of IL,
      and (2) rapid dissolution of lignin and carbohydrates. In this case, the onset of
      the dissolution of these compositions occurred only after the cell wall of
      biomass swelled to a certain extent. Because the first stage was a slow process
      which determined the process reaction rate, it can be deduced that enhancing the
      penetration capacity of IL was crucial for improving the pretreatment efficiency.
      Based on the obtained results, a model was proposed to better understand how the
      plant cell wall responds to the IL before, during, and after pretreatment.

PMID- 24861031
TI  - Relationship between radiation therapy and bullous pemphigoid.
AB  - BACKGROUND: Bullous pemphigoid (BP) is an autoimmune subepidermal blistering
      disease. OBJECTIVE: To review the literature on radiation therapy (RT)-associated
      BP. METHODS: A review of the English language literature on patients who
      developed BP during and up to 10 years post RT was performed. RESULTS: 29
      patients were reported. 25 (86.2%) were women, 84% of whom had received RT for
      breast cancer. Three patients were male (10.3%). Gender was not mentioned in 1
      (3.4%). 72% developed BP post RT; 28% developed BP while undergoing RT. BP was
      initially localized to irradiated sites in 25 patients and to non-irradiated
      sites in 2 patients. Two patients presented with generalized disease. Disease
      control was reported in 12 patients, partial remission in 7 and complete
      remission in 5. CONCLUSION: The clinical profile, response to therapy and
      clinical outcome may indicate that RT-associated BP may be a specific subset of
      BP with a relatively benign course.

PMID- 24861032
TI  - Screening for hepatitis B virus infection in adolescents and adults: a systematic
      review to update the U.S. Preventive Services Task Force recommendation.
AB  - BACKGROUND: In 2004, the U.S. Preventive Services Task Force (USPSTF) recommended
      against screening for hepatitis B virus (HBV) infection. PURPOSE: To update the
      2004 USPSTF review on screening for HBV infection in adolescents and adults. DATA
      SOURCES: MEDLINE (through January 2014), the Cochrane Central Register of
      Controlled Trials, the Cochrane Database of Systematic Reviews, and PsycINFO.
      STUDY SELECTION: Randomized trials of screening and treatment and observational
      studies of screening or the association between intermediate and clinical
      outcomes after antiviral therapy. DATA EXTRACTION: One investigator abstracted
      data, and a second investigator checked them; 2 investigators independently
      assessed study quality. DATA SYNTHESIS: No study directly evaluated the effects
      of screening for HBV infection versus no screening on clinical outcomes.
      Vaccination against HBV infection was associated with decreased risk in high-risk
      populations. On the basis of 11 primarily fair-quality trials, antiviral therapy
      may be more effective than placebo for reducing the risk for clinical outcomes
      associated with HBV infection. However, differences were not statistically
      significant. On the basis of 22 primarily fair-quality trials, antiviral therapy
      was more effective than placebo for various intermediate outcomes, with limited
      evidence that first-line antiviral agents are superior to lamivudine. Antiviral
      therapy was associated with a higher risk for withdrawal due to adverse events
      than placebo, but risk for serious adverse events did not differ. LIMITATION:
      Only English-language articles were included, clinical outcome data for antiviral
      therapies were limited, and several studies were done in countries where the
      prevalence and natural history of HBV infection differ from those of the United
      States. CONCLUSION: Antiviral treatment for chronic HBV infection is associated
      with improved intermediate outcomes, but more research is needed to understand
      the effects of screening and subsequent interventions on clinical outcomes and to
      identify optimal screening strategies. PRIMARY FUNDING SOURCE: Agency for
      Healthcare Research and Quality.

PMID- 24861033
TI  - Serum alanine aminotransferase independently correlates with intrahepatic
      triglyceride contents in obese subjects.
AB  - BACKGROUND AND AIM: Liver enzymes including serum alanine aminotransferase (ALT),
      aspartate aminotransferase (AST) and gamma-glutamyltransferase (GGT) are well
      recognized as surrogate makers reflecting non-alcoholic fatty liver disease
      (NAFLD). However, the associations of serum ALT, AST and GGT with hepatic lipid
      contents are not well established. The aim of this study was to investigate the
      relationship between liver enzymes and intrahepatic triglyceride (IHTG) contents,
      and explore the feasibility in using liver enzymes to reflect accumulation of
      IHTG in obese subjects. METHODS: A cross-sectional analysis was conducted in 475
      obese adults aged 40-65 years. Anthropometric parameters and blood biochemical
      indexes including liver enzymes, glucose and lipid profiles were measured. The
      liver triglyceride contents of subjects were determined by (1)H-MRS. RESULTS:
      Serum ALT, AST and GGT were positively correlated with IHTG contents (p < 0.01).
      Serum ALT, AST and GGT levels at the highest quartile of IHTG contents were
      significantly elevated as compared with those in the lowest quartile (p < 0.01).
      Multivariate linear regression analysis demonstrated that serum ALT, but not AST
      or GGT was independently associated with IHTG contents. By logistic regression
      analysis, the odds ratio for higher IHTG contents was increased by 1.464 times/1
      SD increase in serum ALT level after adjusting for multiple confounding factors
      [OR (95% CI) 2.464 (1.584-3.834)]. However, these relationships could not be
      observed between serum AST or GGT with IHTG contents. CONCLUSIONS: Serum ALT
      level is independently correlated with the hepatic triglyceride contents in obese
      subjects and more appropriate to be used as a predictor for the degree of NAFLD
      rather than AST and GGT.

PMID- 24861034
TI  - Effect of pronase premedication on narrow-band imaging endoscopy in patients with
      precancerous conditions of stomach.
AB  - BACKGROUND: Narrow-band imaging (NBI) endoscopy improves the detection of
      intestinal metaplasia. However, strategies to improve the visibility and
      diagnostic performance of NBI should be sought, as endoscopic views are often
      obscured by the presence of mucus. AIM: To compare the visibility and diagnostic
      performance of NBI endoscopy according to pronase premedication in patients with
      precancerous conditions of the stomach. METHODS: Consecutive outpatients with a
      previous diagnosis of precancerous condition of the stomach were invited to
      undergo a surveillance NBI endoscopy between June and December 2012. Enrolled
      subjects were randomly assigned to pronase or control groups before NBI
      endoscopy. The visibility score and diagnostic performance of NBI endoscopy were
      compared between the two groups. RESULTS: Patients' endoscopic and
      histopathological characteristics were similar between the two groups. Visibility
      score in the proximal part of the stomach and satisfaction score of the
      endoscopist were significantly higher in the pronase group than in the control
      group (p = 0.014 and p = 0.034, respectively). The diagnostic performance of NBI
      endoscopy to detect intestinal metaplasia was not different in either group (both
      p > 0.1). However, the negative predictive value of NBI endoscopy was much
      improved over that of white light endoscopy only in the pronase group (p =
      0.013). CONCLUSION: Pronase premedication increased the visibility of the
      proximal part of the stomach and the satisfaction score during NBI endoscopy.
      Furthermore, negative predictive value of NBI endoscopy was much improved
      compared with that of white light endoscopy after pronase premedication.

PMID- 24861035
TI  - Fabrication and electrical properties of stacked graphene monolayers.
AB  - We develop a simple method to fabricate the two-stacked graphene monolayers and
      investigate the electronic transport in such a system. The independence of the
      two graphene monolayers gives rise to the asymmetric resistance-gate voltage
      curves and an eight-fold degeneracy of Landau level. The position of the maximum
      resistance of the transfer curves shifts towards higher gate voltage with
      increasing magnetic field, which is attributed to the magnetic field induced
      interlayer decoupling of the stacked graphene monolayers. 

PMID- 24861038
TI  - Techniques and applications: Self-like antigens under fire.

PMID- 24861041
TI  - Medical ethics and law: a practical guide to the assessment of the core content
      of learning.

PMID- 24861042
TI  - Accommodating conscience in medicine.

PMID- 24861036
TI  - Microbiological effects of sublethal levels of antibiotics.
AB  - The widespread use of antibiotics results in the generation of antibiotic
      concentration gradients in humans, livestock and the environment. Thus, bacteria
      are frequently exposed to non-lethal (that is, subinhibitory) concentrations of
      drugs, and recent evidence suggests that this is likely to have an important role
      in the evolution of antibiotic resistance. In this Review, we discuss the ecology
      of antibiotics and the ability of subinhibitory concentrations to select for
      bacterial resistance. We also consider the effects of low-level drug exposure on
      bacterial physiology, including the generation of genetic and phenotypic
      variability, as well as the ability of antibiotics to function as signalling
      molecules. Together, these effects accelerate the emergence and spread of
      antibiotic-resistant bacteria among humans and animals. 

PMID- 24861043
TI  - Conscientious objection in Italy.
AB  - The law regulating abortion in Italy gives healthcare practitioners the option to
      make a conscientious objection to activities that are specific and necessary to
      an abortive intervention. Conscientious objectors among Italian gynaecologists
      amount to about 70%. This means that only a few doctors are available to perform
      abortions, and therefore access to abortion is subject to constraints. In 2012
      the International Planned Parenthood Federation European Network (IPPF EN) lodged
      a complaint against Italy to the European Committee of Social Rights, claiming
      that the inadequate protection of the right to access abortion implies a
      violation of the right to health. In this paper I will discuss the Italian
      situation with respect to conscientious objection to abortion and I will suggest
      possible solutions to the problem. 

PMID- 24861045
TI  - Fluorescein angiography and spectral-domain optical coherence tomography for
      monitoring anti-VEGF therapy in myopic choroidal neovascularization.
AB  - AIM: To evaluate the agreement between fluorescein angiography (FA) and spectral
      domain optical coherence tomography (SD-OCT) in detecting myopic choroidal
      neovascularization (CNV) activity during bevacizumab treatment. METHODS: Thirty
      four patients with subfoveal myopic CNV were prospectively enrolled. FA and SD
      OCT were performed at baseline and at all planned monthly visits. After the first
      injection, additional treatments were administered following detection of fluid
      on SD-OCT and/or leakage on FA. kappa-Analysis was performed to examine the
      agreement between FA and SD-OCT. RESULTS: At baseline, FA and SD-OCT agreed in
      26/34 cases (kappa=0.23); sensitivity and specificity were 77.4 and 66.7%,
      respectively. Seven eyes presented leakage on FA with no fluid on SD-OCT, 1 case
      showed intraretinal fluid on SD-OCT and no leakage on FA. At the 1-month
      examination, specificity and kappa-value improved, and 30/34 cases showed
      complete concordance. At the 3- and 4-month examinations, a discordance was noted
      in 6 cases. From the 5-month examination on, a correspondence was achieved in at
      least 30/34 cases and reached a perfect match in 11 sessions. CONCLUSIONS: Our
      study confirms the key role of FA in diagnosing myopic CNV. It seems possible
      there may be a role for SD-OCT in assisting FA to monitor the myopic CNV activity
      during anti-vascular endothelial growth factor antibody treatment.

PMID- 24861044
TI  - Short leukocyte telomere length is associated with obesity in American Indians:
      the Strong Heart Family study.
AB  - Shorter leukocyte telomere length (LTL) has been associated with a wide range of
      age-related disorders including cardiovascular disease (CVD) and diabetes.
      Obesity is an important risk factor for CVD and diabetes. The association of LTL
      with obesity is not well understood. This study for the first time examines the
      association of LTL with obesity indices including body mass index, waist
      circumference, percent body fat, waist-to-hip ratio, and waist-to-height ratio in
      3,256 American Indians (14-93 years old, 60% women) participating in the Strong
      Heart Family Study. Association of LTL with each adiposity index was examined
      using multivariate generalized linear mixed model, adjusting for chronological
      age, sex, study center, education, lifestyle (smoking, alcohol consumption, and
      total energy intake), high-sensitivity C-reactive protein, hypertension and
      diabetes. Results show that obese participants had significantly shorter LTL than
      non-obese individuals (age-adjusted P=0.0002). Multivariate analyses demonstrate
      that LTL was significantly and inversely associated with all of the studied
      obesity parameters. Our results may shed light on the potential role of
      biological aging in pathogenesis of obesity and its comorbidities.

PMID- 24861046
TI  - Comparison of small-bowel mucosal injury between low-dose aspirin and non-aspirin
      non-steroidal anti-inflammatory drugs: a capsule endoscopy study.
AB  - BACKGROUND/AIMS: The differences in the severity of small-bowel toxicity induced
      by aspirin and non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs) remain
      unclear. This study aimed at clarifying these differences in small-bowel mucosal
      injury by using capsule endoscopy (CE). METHODS: We retrospectively compared the
      records of 78 and 40 obscure gastrointestinal bleeding patients receiving low
      dose aspirin (LDA) and non-aspirin NSAIDs, respectively. All patients were found
      to have small-bowel mucosal injuries on CE. The two groups were compared for the
      number of small-bowel mucosal injuries and CE scores on the basis of the findings
      of CE. RESULTS: The mean numbers of reddened lesions in the LDA group and non
      aspirin NSAID group were 2.49 +/- 3.15 and 1.65 +/- 3.04; the mean numbers of
      erosions/ulcers 1.56 +/- 3.75 and 6.08 +/- 10.4, and the mean CE scores 154 +/-
      294 and 520 +/- 758, respectively. The mean number of reddened lesions was
      significantly higher and the mean number of erosions/ulcers and CE scores
      significantly lower in the LDA group than in the other non-aspirin NSAID group.
      CONCLUSION: Small-bowel mucosal injuries were significantly milder in the LDA
      group than in the non-aspirin NSAID group, though reddened lesions were more
      frequent in the LDA group.

PMID- 24861047
TI  - Periorbital chloroma mimicking raccoon eyes in a child with acute myeloid
      leukaemia.

PMID- 24861048
TI  - Question 1: Ultrarapid intravenous rehydration in children who are dehydrated
      from viral gastroenteritis: does it work?

PMID- 24861049
TI  - Six-year follow-up study on the effect of combined anterior and posterior spinal
      fusion on lung function and quality of life in young people with adolescent
      idiopathic scoliosis.
AB  - OBJECTIVES: The effects of spinal surgery on lung function and quality of life
      (QoL) are important patient outcomes. Long-term follow-up of lung function and
      QoL in those undergoing combined anterior and posterior spinal fusion (A/PSF) for
      adolescent idiopathic scoliosis (AIS) is poorly documented with only one study
      extending beyond 2 years, though available evidence points to a decrement in lung
      function. Our study evaluated long-term change in lung function and QoL following
      A/PSF for AIS. DESIGN: Prospective cohort study. PATIENTS: Patients with AIS.
      SETTING: Tertiary paediatric respiratory centre and national spinal service.
      DESIGN: Spirometry was performed along with QoL (Scoliosis Research Society-22
      (SRS-22) questionnaire). Paired t test and one-way analysis of variance were used
      to compare pre-A/PSF and post-A/PSF data. RESULTS: Data were available for 12
      patients (9 female) who underwent A/PSF at mean 13.8 (range 11.8-15) years. Mean
      follow-up was undertaken 5.8 (range 4.1-6.8) years postoperatively. Height
      increased from mean (SD) 169 (9) cm preoperatively to 175 (5) cm at follow-up
      (p<0.01). Scoliosis corrected from 100 (15) degrees  to 29 (11) degrees 
      (p<0.001). Mean (SD) forced expiratory volume in 1 s was -3.4 (1.4) z scores
      preoperatively versus -3.3 (1) z scores postoperatively (p=0.85); and forced
      vital capacity was -3.4 (1.7) ) z scores pre-A/PSF and -3.4 (1.1) z scores post
      A/PSF (p=0.83). SRS-22 scores improved mean (SD) of 3.6 (0.3) preoperatively to
      4.2 (0.3) at 2 years postoperatively, and 4.4 (0.4) at 6 year follow-up (p<0.001,
      analysis of variance). High patient satisfaction rates (4.8 (0.3)) were recorded.
      No correlation was noted between changes in forced expiratory volume in 1 s (r=
      0.15, p=0.63) or forced vital capacity (r=-0.12, p=0.71) and change in long-term
      SRS-22 score. CONCLUSIONS: Long-term follow-up of patients with AIS suggests no
      deficit in pulmonary function, while QoL shows incremental improvement and
      patient satisfaction is high over 6 years after A/PSF.

PMID- 24861050
TI  - Joint hypermobility syndrome subclassification in paediatrics: a factor analytic
      approach.
AB  - OBJECTIVE: To determine if exploratory factor analysis can identify subtypes
      comprising recognisable clinical patterns of the presenting signs and symptoms of
      children with joint hypermobility syndrome (JHS). PATIENTS: Eighty-nine children
      with JHS aged 6-16 years. METHODS: Twelve tests comprising anthropometric,
      musculoskeletal and functional assessments were conducted. Signs, symptoms and
      family history were recorded. Exploratory factor analysis was performed, factor
      scores generated, and correlations calculated to identify associations. RESULTS:
      Sixty-six percent of the variance in the score set could be accounted for by five
      JHS subtypes (Eigenvalues >1). Factor 1, 'joint affected' JHS, had loadings on
      multiple joint pain, recurrent joint instability and postural orthostatic
      hypotension symptoms, and factor scores were associated with worse pain (r=0.48,
      p<0.01), fatigue (r=-0.54, p<0.01) and reduced health-related quality of life
      (HRQOL) (r=-0.5, p<0.01). Factor 2, 'athletic' JHS, loaded on muscle endurance,
      balance and motor skill proficiency, and scores were associated with less fatigue
      (r=0.3, p<0.01) and better HRQOL (r=0.44, p<0.01). Factor 3, 'systemic' JHS,
      loaded on skin involvement, incontinence symptoms, bowel involvement and
      recurrent joint instability, and was associated with reduced HRQOL (r=-0.24,
      p=0.03). Factor 4, 'soft tissue affected' JHS, loaded on recurrent soft tissue
      injuries and reduced muscle length, and was associated with greater fatigue (r=
      0.43, p<0.01) and reduced HRQOL (r=-0.44, p<0.0001). Factor 5, 'high BMI' JHS,
      had high loadings on body mass index (BMI) for age, muscle endurance and no
      gastrointestinal involvement, and was associated with higher pain (r=0.33,
      p<0.01). CONCLUSIONS: The presenting signs and symptoms of children with JHS can
      be summarised in five clinically recognisable subtypes.

PMID- 24861051
TI  - Galectin-1 and -9 in angiogenesis: a sweet couple.
AB  - The growth of new blood vessels out of the pre-existing vasculature, i.e.,
      angiogenesis, is executed by endothelial cells that normally form the inner
      lining of blood vessels. During angiogenesis, these cells exert different
      activities which require interactions with other cells and with the extracellular
      environment. It has become evident that this frequently involves galectins since
      the members of this protein family facilitate interactions between cells and/or
      glycoproteins via carbohydrate binding. In addition, they can regulate
      intracellular processes like signaling and splicing via non-carbohydrate
      interactions. We have previously reported on the role of galectin-1 and -9 in
      endothelial cell function. Here, we review the current knowledge of these two
      galectins in endothelial cell biology and angiogenesis. In addition, we describe
      the contribution of both galectins to other processes that involve the
      endothelium, including inflammation and coagulation. Finally, we discuss the
      challenges for future research in order to better understand how this "sweet"
      couple exerts its multifunctional activities within the vasculature. 

PMID- 24861052
TI  - Galectins and neovascularization in central nervous system tumors.
AB  - Despite advances in diagnosis and treatment, the overall outcomes for patients
      with brain tumors remain unpredictable. New prognostic markers are still needed
      to identify high-risk patients for whom the standard treatment has poor outcomes
      and would thus be well suited for more aggressive therapies. Neovascularization
      has long been implicated as a salient feature of glioma progression. In fact,
      high-grade gliomas are among the most vascular of all solid tumors, and vascular
      proliferation is a pathological hallmark of glioblastomas. Galectins are known to
      play important roles in cancer biology, including cancer cell migration, tumor
      immune escape or tumor angiogenesis. Moreover, galectins were reported to be
      involved in glioma progression. Given the key role of angiogenesis in brain
      tumors, the expression of galectins in tumor-associated endothelial cells (EC)
      and the implication of galectins in angiogenesis, the present review will focus
      on the expression of galectins in ECs of normal brain and brain tumors. 

PMID- 24861053
TI  - Precision genome editing: a small revolution for glycobiology.
AB  - Precise and stable gene editing in mammalian cell lines has until recently been
      hampered by the lack of efficient targeting methods. While different gene
      silencing strategies have had tremendous impact on many biological fields, they
      have generally not been applied with wide success in the field of glycobiology,
      primarily due to their low efficiencies, with resultant failure to impose
      substantial phenotypic consequences upon the final glycosylation products. Here,
      we review novel nuclease-based precision genome editing techniques enabling
      efficient and stable gene editing, including gene disruption, insertion, repair,
      modification and deletion. The nuclease-based techniques comprised of homing
      endonucleases, zinc finger nucleases, transcription activator-like effector
      nucleases, as well as the RNA-guided clustered regularly interspaced short
      palindromic repeat/Cas nuclease system, all function by introducing single or
      double-stranded breaks at a defined genomic sequence. We here compare and
      contrast the different techniques and summarize their current applications,
      highlighting cases from the field of glycobiology as well as pointing to future
      opportunities. The emerging potential of precision gene editing for the field is
      exemplified by applications to xenotransplantation; to probing O-glycoproteomes,
      including differential O-GalNAc glycoproteomes, to decipher the function of
      individual polypeptide GalNAc-transferases, as well as for engineering Chinese
      Hamster Ovary host cells for production of improved therapeutic biologics.

PMID- 24861056
TI  - Quantifying stroke coordination during the breathing action in front-crawl
      swimming using an instantaneous net drag force profile.
AB  - This study used both an instantaneous net drag force profile and a symmetry
      timing to evaluate the effect of the breathing action on stroke coordination.
      Twenty elite swimmers completed a total of six randomised front-crawl towing
      trials: (i) three breathing trials and (ii) three non-breathing trials. The net
      drag force was measured using an assisted towing device mounted upon a Kistler
      force platform, and this equipment towed the swimmer at a constant speed. The net
      drag force profile was used to create a stroke symmetry index for each swimming
      trial. Analysis using the symmetry indices identified that the majority of
      participants demonstrated an asymmetrical instantaneous net drag force stroke
      profile in both the breathing and non-breathing conditions, despite no
      significant differences in the time from finger-tip entry to finger-tip exit.
      Within the breathing condition, the faster swimmers compared to the slower
      swimmers demonstrated a lesser percentage of overlap between stroke phases on
      their breathing stroke side. During the non-breathing condition, the faster
      participants compared to the slower swimmers recorded a reduction in the
      percentage of overlap between stroke phases and less duration in the underwater
      stroke on their breathing stroke side. This study identified that the majority of
      participants demonstrated an asymmetrical net drag force profile within both
      conditions; however, asymmetry was less prevalent when examining with only the
      timing symmetry index.

PMID- 24861057
TI  - Organizational changes in ABEn and the Center for Social Communication and
      Publications.

PMID- 24861055
TI  - Epigenetic manipulation restores functions of defective CD8+ T cells from chronic
      viral infection.
AB  - Functional exhaustion of antigen-specific T cells is a defining characteristic of
      many chronic infections, but the underlying mechanisms of T cell dysfunction are
      not well understood. Epigenetics plays an important role in the control of T cell
      development, differentiation, and function. To examine if epigenetics also plays
      a role in T cell exhaustion, we analyzed chromatin remodeling in CD8(+) T cells
      from mice with chronic lymphocytic choriomeningitis virus infection. We observed
      downregulation of diacetylated histone H3 in both virus-specific and total CD8(+)
      T cells, and functional defects not only in virus-specific CD8(+) T cells but
      also within the total CD8(+) T cell population. In vitro treatment of these
      exhausted CD8(+) T cells with histone deacetylase inhibitors restored
      diacetylated histone H3 levels, and improved their immune functions. Upon
      adoptive transfer, these treated CD8(+) T cells developed into functional memory
      T cells in vivo that enhanced protective immunity. These results define a role of
      epigenetics in T cell exhaustion and suggest epigenetic manipulation as a novel
      molecular therapy to restore immune functions. 

PMID- 24861058
TI  - [The family in the Pediatric Unit: living with rules and hospital routines].
AB  - The study aimed to know, in Foucault's view, how the family caregiver of the
      child deals with the rules and routines in the hospital. Descriptive qualitative
      study, conducted in the second half of 2011. It had the Grounded Theory as
      methodological framework. It was developed in the pediatric unit of a university
      hospital in southern Brazil, with eighteen family caregivers. The data collection
      was performed by semi-structured interviews and the analysis through open, axial
      and selective coding. It was noticed that the family tends to conform to such
      rules and routines in the hospital, but recognizes the importance of its
      flexibility, exercising endurance, as dialoguing, or as trespassing such rules
      and routines, in search of autonomy, when they realize that these do not address
      their needs. It is important to use rules and routines to enable the family
      practices and spaces of freedom, autonomy and resistance. 

PMID- 24861054
TI  - Blockade of ActRIIB signaling triggers muscle fatigability and metabolic
      myopathy.
AB  - Myostatin regulates skeletal muscle size via the activin receptor IIB (ActRIIB).
      However, its effect on muscle energy metabolism and energy-dependent muscle
      function remains largely unexplored. This question needs to be solved urgently
      since various therapies for neuromuscular diseases based on blockade of ActRIIB
      signaling are being developed. Here, we show in mice, that 4-month
      pharmacological abrogation of ActRIIB signaling by treatment with soluble ActRIIB
      Fc triggers extreme muscle fatigability. This is associated with elevated serum
      lactate levels and a severe metabolic myopathy in the mdx mouse, an animal model
      of Duchenne muscular dystrophy. Blockade of ActRIIB signaling downregulates
      porin, a crucial ADP/ATP shuttle between cytosol and mitochondrial matrix leading
      to a consecutive deficiency of oxidative phosphorylation as measured by in vivo
      Phosphorus Magnetic Resonance Spectroscopy ((31)P-MRS). Further, ActRIIB blockade
      reduces muscle capillarization, which further compounds the metabolic stress. We
      show that ActRIIB regulates key determinants of muscle metabolism, such as
      Pparbeta, Pgc1alpha, and Pdk4 thereby optimizing different components of muscle
      energy metabolism. In conclusion, ActRIIB signaling endows skeletal muscle with
      high oxidative capacity and low fatigability. The severe metabolic side effects
      following ActRIIB blockade caution against deploying this strategy, at least in
      isolation, for treatment of neuromuscular disorders.

PMID- 24861059
TI  - [Applicability of theoretical model to families of children with chronic disease
      in intensive care].
AB  - This study examines the applicability of the theoretical model "Looking to
      maintain the balance to meet the demands and take care of the hospitalized child"
      to families of children with chronic diseases in intensive care. This is a
      qualitative study that complied with Resolution 466/2012, and was approved by the
      Ethics Committee through the Resolution 0111.0.441.099-11. The Grounded Theory
      was adopted as methodological framework. The data were collected through semi
      structured interviews with seven families of children hospitalized for chronic
      diseases. The research identified three phenomena, which were analyzed according
      to the theoretical model cited above: Difficult experience for the family;
      Modifying the functioning and family routine; and Receiving support in coping
      with chronic illness. The study showed that the theoretical model used can be
      applied to families of children with chronic illnesses because they experience an
      unexpected event that disrupts their daily life and demand the search for new
      strategies for coping. 

PMID- 24861060
TI  - [Early neonatal mortality related to clinical interventions].
AB  - Descriptive cross-sectional study that aimed at verifying the influence of
      clinical interventions carried out in the delivery room and in the Neonatal ICU
      in the early neonatal death, in Cuiaba-MT, 2010. The data collection was
      performed in January-February 2011, based on the data found in the live birth
      certificates, death certificates and hospital records, filed and examined in the
      SPSS program version 15.0. Of the 77 deaths analyzed, 94.7% of the babies were
      born in a hospital and more than 70% died early. The interventions in the
      delivery room that were associated to the risk of early death were
      cardiopulmonary resuscitation and intubation; during the hospital stay, the
      central catheter of peripheral insertion and the blood transfusion were
      associated as protection factors for early death. Knowing about which of these
      clinical practices are beneficial or harmful to the neonate's health is essential
      to reach the quality of care and, consequently, to reduce the neonatal deaths,
      mainly the early ones. 

PMID- 24861061
TI  - [Experiencing skin to skin contact with the baby during the postpartum period as
      a mechanical act].
AB  - The objective was to understand the puerpera's experience during the first skin
      to skin contact with the newborn in the immediate postpartum period, the
      obstetric ward of a public hospital in a city in Bahia. Exploratory, descriptive
      and qualitative study, approved by the Ethics Committee and conducted with
      fourteen postpartum women, through semi-structured interviews in the period July
      August 2011. The data were analyzed using Grounded Theory, identifying the
      phenomenon "Experiencing skin to skin contact as a mechanical act" and its three
      subcategories: "Encouraging the only contact", "Contact as a mechanical act" and
      "Being forced to initiate breastfeeding. "Encouraging the skin to skin contact
      and immediate breastfeeding occur mechanically, being highlighted only the
      contact, requiring the puerperas to initiate breastfeeding in sudden and abrupt
      manner, not respecting their willingness to perform or not this practice. 

PMID- 24861062
TI  - [Infant mortality due to avoidable causes in a city in Northeastern Brazil].
AB  - This is a cross-sectional study that aimed to describe the occurrence of infant
      mortality in Recife (PE) between 2000 and 2009, second to avoidable causes. The
      population composed of cases of deaths between 2000 and 2009 among the infants of
      mothers living in Recife. Deaths were classified as avoidable by using the List
      of avoidable causes of deaths resulting from interventions within the Brazilian
      National Health System (SUS). Descriptive statistics were used for data analysis.
      A decrease in the infant mortality coefficient from 20.4 to 12.1 per 1.000 live
      births was observed (reduction of 40.6%). From the total of 3.743 deaths
      registered, 2.861 (76.4%) were classified as avoidable. It was notable that 61.2%
      of the deaths could have been avoided through appropriate care for the woman
      during the pregnancy. An approach in which avoidability is analyzed may assist in
      discussions relating to organization, quality and access to healthcare service,
      and in identifying deaths that could have been avoided through appropriate mother
      child healthcare. 

PMID- 24861063
TI  - [Caring network for children with special health needs].
AB  - The study aimed to characterize the institutions to support children with special
      health care needs and apprehend how to happen the interactions between these
      institutions and the other services that make up the network of care. This is a
      descriptive and exploratory study with qualitative approach. Ten people
      responsible for institutions which assist this clientele participated in this
      study. Semi structured interview was used as the instrument of data collection.
      The institutions assist approximately 3310 clients, with 432 children; eight
      assist beyond their capabilities and the pent-up demand is 200 patients; two have
      24 hour care; most are non-governmental and the funding sources consist of
      donations, own and transfer government resources. With regard to the dynamics of
      the work process, integration and deficient articulation were mentioned. It is
      necessary to reorganize the services in order to have a qualified and integrative
      care, minimizing the difficulties of communication and cooperation among
      services. 

PMID- 24861065
TI  - [Overburden on elderly's family caregivers: association with characteristics of
      the elderly and care demand].
AB  - This is an epidemiological research, descriptive and transversal, which had as
      objectives to estimate the prevalence of overburden among family caregivers of
      dependent elderly in the city of Joao Pessoa, Paraiba, and to identify its
      relationship with the elderly's conditions of health, functionality and demand
      for care. The population comprised 240 elderly people residents in the twenty
      census sectors in the referred city. The sample was composed of 52 elderly people
      with functional inability and their caregivers. To data collection, it was
      applied a structured questionnaire and the scales of Mini Mental State
      Examination, Katz Index and Burden Interview. The results demonstrated that 84.6%
      of caregivers showed overburden, which was associated with clinical and
      functional characteristics of the elderly and with the demand for care. The
      findings bring relevant contributions to the elaboration of public policies in
      order to establish formal support for families' caregivers. 

PMID- 24861064
TI  - [Experience of mothers on having a child diagnosed and hospitalized by the virus
      Influenza A (H1N1)].
AB  - The study aimed to understand the experience of having a child hospitalized with
      Influenza A (H1N1). This qualitative study was conducted with five mothers of
      children living in Maringa-PR, hospitalized with this diagnosis, during the years
      2009 and 2010. Data were collected in households, through semi-structured
      interviews and subjected to thematic content analysis. The diagnosis and the need
      for isolation caused great impact on families, triggering uncertainty about the
      future of children. Mothers indicated the lack of information related to the
      disease and isolation as a source of insecurity and, difficulties to follow the
      hospital routines and even in family relationships. There is need for nursing
      professionals to understand that this is a difficult time for the family,
      especially for the mother, being necessary to seek ways to minimize its effects.
      The bond and the provision of information can facilitate the process of
      hospitalization / isolation of the child. 

PMID- 24861066
TI  - [Care relationship between the family caregiver and the elderly with Alzheimer].
AB  - Cross-sectional quantitative and qualitative-descriptive study, aimed to
      interpret the relationship in the caring of family caregivers and Alzheimer's
      elderly sufferers, grounded in the concrete dialectic of participation according
      to Gabriel Marcel's four precepts. The convenience sample entailed 208 family
      caregivers in the quantitative and 36 in the qualitative aspect. The caregivers
      were women (n=178, 86%), aged 22-83 years, living with the elderly (n=169, 81%),
      with more than eight years of formal education (n=147, 71%), not having an
      occupation (n=121, 58%) and with mild burden (n=96, 46.2%). The synthesis theme
      was The order of mystery pervaded by faith and supported by hope. The
      relationship between family members and Alzheimer's elderly sufferer encompasses
      love, faithfulness, hope and presence. Interpreting this relationship enables
      nurses to develop sensitivity and creativity for professional practice, taking
      into account the subjectivity and mystery in human relations. 

PMID- 24861068
TI  - [Cognitive profile of elderly residents in Long-stay Institutions of Brasilia
      DF].
AB  - Aging exposes the individuals to a number of limitations, such as the physical,
      nutritional and cognitive, which can cause them to hospitalization in long-stay
      institutions. In this study, it was aimed to evaluate to evaluate the cognitive
      profile of elderly institutionalized through three instruments. Sixty
      institutionalized elderly people in long-stay institutions underwent assessment
      through the Mini Mental State Examination (MMSE), the Trail Making Test and the
      Clinical Dementia Rating. It was found that the percentage of seniors with
      cognitive impairment by the MMSE was 30% of the sample, being more prevalent in
      women (36.2% of cognitive loss) compared to men (7.7% of cognitive loss). There
      was no consistency between the results obtained by the MMSE with the other
      instruments tested. 

PMID- 24861067
TI  - [Health conditions of elderly residents in Long-stay Institution second basic
      human needs].
AB  - The study aimed to characterize the elderly residents in long-stay nursing homes
      (HHs) according to gender, age, education, cause of admission and length of stay;
      and to describe their health conditions according to the theory of Basic Human
      Needs. This was an analytical, observational and cross-sectional study with a
      quantitative approach, conducted with 86 seniors from eight NHs in a city of
      Triangulo Mineiro, state of Minas Gerais. For data analysis, it was used the
      descriptive statistics, simple and average frequency and standard deviation. The
      elderly were predominantly female (70.9 %), 80 years or older (44.2 %) and
      illiterate (48.8 %). The physiological needs affected were: high blood pressure
      (30.2 %); cognitive decline (58.7 %) and urinary incontinence (50 %). As
      psychosocial needs, everyone was dependent to perform the instrumental activities
      of daily living and 52.3 % have indicative of depression. As for the
      psicoespiritual needs, 70.9 % did not practice any religion. The basic human
      needs identified as affected were contributing to a decreased on the quality of
      life of seniors. 

PMID- 24861069
TI  - [Styles of nurses' caring in Intensive Therapy mediated by technology].
AB  - The objective was to identify the social representations of the intensive therapy
      nurses about the care practices in face of the technology. Participant
      observation and interviews were conducted with twenty one nurses of an intensive
      therapy center, at a Rio de Janeiro public hospital. Lexical analysis was
      applied, using the Alceste 2010. The results were organized in two categories,
      each of them with three lexical classes. The first brought the meaning of the
      technology in intensive therapy and the organization of the styles of caring; the
      second showed the client's condition and its impact on nurses' care practices. It
      was concluded that the technology organizes the nurses' styles of caring, that
      are built on client assistance in the work context. These lead nurses to assign
      meaning to their practices driving them to the elaboration of ways of acting in
      face of the technologies. 

PMID- 24861070
TI  - [Profile of users assisted in a non-hospital emergency unit].
AB  - This is a descriptive study, of a quantitative approach, that aimed to evaluate
      the profile of adult patients assisted in a non-hospital emergency care unit of a
      countryside city of Sao Paulo state, Brazil. A sample of 477 records, selected by
      systematic random sampling technique of all the consultations performed in 2011,
      was analyzed. The population assisted was, mostly, of young women, aged 20-29
      years, from the area covered by the service unit and the assistance occurred in
      the period of operation of the primary health care network. The reasons for
      seeking health care were complaints of low severity. Given that the service is
      intended to meet urgent situations of medium and high complexity, there is a need
      to introduce the user's embracement and the risk classification in order to
      improve the organization and quality of care provided to the population. 

PMID- 24861071
TI  - [Adherence of people with type 2 diabetes mellitus to drug treatment].
AB  - This cross-sectional and quantitative study aimed to evaluate the adherence to
      drug treatment of the people with diabetes mellitus and its relation to clinical,
      treatment and metabolic control variables. Sample consisted of 162 people with
      type 2 diabetes mellitus on follow-up outpatient care. The Measure of Treatment
      Adherence and consultation to the participants' medical records were used for
      data collection. A high adherence to drug treatment was obtained. For a p<0.05,
      it was obtained an inverse correlation with diastolic blood pressure and a direct
      correlation with the frequency of daily administration of insulin and oral
      antidiabetic agents. There were no statistically significant correlations between
      adherence and metabolic control variables. Results diverge from the literature
      regarding the adherence to drug treatment in chronic diseases, as well as in the
      correlation between adherence and complexity of drug regimen, which points to the
      need for more studies on this theme. 

PMID- 24861072
TI  - [The family in the practices of Family Health teams].
AB  - Exploratory, qualitative study, that aimed to analyze the "centrality in the
      family", a Family Health Strategy (FHS) attribute, examining how the family
      context is considered in the practice of health professionals, through the
      analysis of health practices directed to families in Manaus-AM, Brazil.
      Interviews, participant observation and the focus groups were used as techniques
      for data collection. Informants were FHS teams professionals and families
      members. The focus on family was analyzed in two dimensions, called: a) Deploying
      a new family-centered care model and b) Incorporating the family as the center of
      care in the new health care model. The results showed low intensity of focus on
      the family in health practices. The family is not the center of attention in the
      FHS in Manaus and practices of professionals within the FHS teams still focus on
      individuals. 

PMID- 24861073
TI  - [Natural childbirth and cesarean section: social representations of women who
      experienced them].
AB  - Aiming to understand the social representations of natural childbirth and
      caesarean section for women who experienced them, it was developed a descriptive,
      qualitative research. Interviews were conducted from July to October 2010, with
      twenty women who experienced both types of birth. The number of participants was
      determined by theoretical saturation during data collection and content analysis.
      The results showed, during the experience of motherhood: the search for
      information, the experience of childbirth alone versus support at birth; and that
      the woman has no option of choice on type of birth. Natural childbirth includes
      important issues such as: the ambivalence of feelings, positive perception and
      hospitalization. Cesarean section is associated with ambivalence of feelings,
      understood as a solution of a problem and the preference for cesarean section.
      The natural childbirth is a challenge for women, but the positive feelings
      outweigh the difficulties, while the cesarean section is associated to the
      physical benefits of its execution. 

PMID- 24861074
TI  - [Mothers' knowledge about exclusive breastfeeding].
AB  - This is a descriptive study, with a qualitative approach, aimed to identify the
      knowledge of puerperal women on exclusive breastfeeding. Data were collected
      between September-October 2011, through semi-structured interview. Thirteen
      puerperal women, interned in a rooming unit of a public institution in the city
      of Caxias do Sul-RS, participated in the study. Data analysis was performed using
      thematic analysis. From the interpretation of information three categories
      emerged: the knowledge about exclusive breastfeeding, the breastfeeding process
      and the influences of received information. Even getting information from health
      professionals in the prenatal period, it is possible to understand that there is
      a need to improve communication and monitoring of mothers, as a continuity of
      professional care in the postpartum period, and also later, in the remote. 

PMID- 24861075
TI  - [Prevalence of common mental disorders in nursing workers at a hospital of
      Bahia].
AB  - This study aimed to describe the prevalence of "suspected" of common mental
      disorders (CMD) in nursing workers at a general hospital in the state of Bahia.
      It was carried out a cross-sectional epidemiological study with 309 nursing
      workers, who worked in welfare activities in a large hospital. The nurses
      mentioned overwork and low pay. The most frequent health complaints were related
      to body posture and mental health. The overall prevalence of "suspected" of CMD
      was 35.0%. Regarding the psychosocial aspects of work, it was reported high
      psychological demand and low control over their work activities. The results
      indicated that the working and health conditions observed are not suitable for
      the effective realization of nursing work in the hospital. 

PMID- 24861076
TI  - [Quality of work life in nursing staff].
AB  - This article deals with aspects that are related to work, quality of life, and
      its relationship with the nursing staff within the Mexican context. Professionals
      in health areas present alterations that are commonly overlooked and barely dealt
      with, especially when the person is a woman and, the care they give to patients,
      families, and/or friends, or community members, precede their own self care. In
      the case of institutions or work areas, even when the job provides human beings
      with several benefits, it usually lacks the proper conditions to perform the job,
      carries negatives aspects or pathological conditions, all which can relate to
      poor levels of Quality of Life at Work. Members of the nursing team need to
      perform their work in the best possible conditions in order to maintain their
      physical and mental health. 

PMID- 24861077
TI  - [Conceptual reflections on health humanization: conception of nurses from
      Intensive Care Units].
AB  - The National Policy of Care Humanization and Health System Management are
      configured as a complex public policy which encompasses the structural, technical
      and relational aspects of the health service. However, this policy has failed at
      establishing the boundaries of its activities and the conceptual aspects of the
      humanization term. This study aimed to perform a reflection about the
      humanization of health through a conceptual analysis of the term itself and in
      the interpretation of speeches of nurses working in Intensive Care Units,
      collected in a qualitative research. It was concluded that nurses have an
      intuitive insight of the definition of humanization, understanding the necessity
      of conducting a holistic assistance beyond mere technique and also covering the
      physiological, psychological, social and spiritual aspects of care. At the same
      time they demonstrate the lack of preparation in professional education for the
      implementation of this humanized assistance. 

PMID- 24861078
TI  - Targeting angiogenic pathway for chemoprevention of experimental colon cancer
      using C-phycocyanin as cyclooxygenase-2 inhibitor.
AB  - An angiogenic pathway was studied that involved stromal tissue degradation with
      matrix metalloproteinases (MMPs), vesicular endothelial growth factor-A (VEGF-A),
      and hypoxia inducible factor-1alpha (HIF-1alpha) mediated growth regulation in a
      complex interaction with chemokines, such as monocyte chemoattractant protein-1
      (MCP-1) and macrophage inflammatory protein-1beta (MIP-1beta). Gene and protein
      expression was studied with real-time PCR, Western immunoblot, and
      immunofluorescence. Morphological and histopathological analysis of tumor was
      done, as also the activity of MMPs and HIF-1alpha by gelatin zymography and
      ELISA. Binding interactions of proteins were studied by molecular docking.
      Piroxicam, a traditional NSAID and C-phycocyanin, a biliprotein from Spirulina
      platensis, were utilized in the chemoprevention of DMH-induced rat colon cancer.
      A significant number of tumors was evident in DMH treated animals, while with
      piroxicam and C-phycocyanin, the number and size of tumors/lesions were reduced.
      Colonic tissues showed severe dysplasia, tubular adenoma, and adenocarcinoma from
      DMH, with invasive features along with signet ring cell carcinoma. No occurrence
      of carcinoma was detected in either of the drug treatments or in a combination
      regimen. An elevated VEGF-A, MMP-2, and MMP-9 level was observed, which is
      required for metastasis and invasion into surrounding tissues. Drugs induced
      chemoprevention by down-regulating these proteins. Piroxicam docked in VEGF-A
      binding site of VEGF-A receptors i.e., VEGFR1 and VEGFR2, while phycocyanobilin
      (a chromophore of C-phycocyanin) docked with VEGFR1 alone. HIF-1alpha is up
      regulated which is associated with increased oxygen demand and angiogenesis. MCP
      1 and MIP-1beta expression was also found altered in DMH and regulated by the
      drugs. Anti-angiogenic role of piroxicam and C-phycocyanin is well demonstrated. 

PMID- 24861079
TI  - Cervical spine involvement as initial manifestation of rheumatoid arthritis: a
      case report.
AB  - Rheumatoid arthritis' synovitis affects mostly small hand and feet joints,
      although it may compromise any joint with a synovial lining. Cervical involvement
      occurs usually in longstanding disease in over half of these patients. We report
      the case of a 35-year old male patient who was referred to our outpatient clinic
      for a 2-year severe and disabling inflammatory neck pain, with incomplete
      response to intramuscular non-steroidal anti-inflammatory drugs and unremarkable
      cervical imaging studies. He also mentioned self-limited episodes of symmetric
      polyarthralgia involving hands, wrists, elbows, knees and feet, which started
      after his cervical complaints. On laboratorial workup, positive rheumatoid factor
      and anti-citrullinated peptide antibody and negative HLA-B27 were found. Cervical
      spine magnetic resonance imaging revealed atlantoaxial subluxation and odontoid
      process inflammatory pannus and erosions. Rheumatoid arthritis with cervical
      spine involvement as initial manifestation of disease was the definite diagnosis.
      The patient was started on methotrexate and prednisone and he was referred to
      neurosurgery outpatient clinic for cervical spine fixation.

PMID- 24861080
TI  - Epidermal growth factor impairs palatal shelf adhesion and fusion in the Tgf-beta
      3 null mutant.
AB  - The cleft palate presented by transforming growth factor-beta3 (Tgf-beta3) null
      mutant mice is caused by altered palatal shelf adhesion, cell proliferation,
      epithelial-to-mesenchymal transformation and cell death. The expression of
      epidermal growth factor (EGF), transforming growth factor-beta1 (Tgf-beta1) and
      muscle segment homeobox-1 (Msx-1) is modified in the palates of these knockout
      mice, and the cell proliferation defect is caused by the change in EGF
      expression. In this study, we aimed to determine whether this change in EGF
      expression has any effect on the other mechanisms altered in Tgf-beta3 knockout
      mouse palates. We tested the effect of inhibiting EGF activity in vitro in the
      knockout palates via the addition of Tyrphostin AG 1478. We also investigated
      possible interactions between EGF, Tgf-beta1 and Msx-1 in Tgf-beta3 null mouse
      palate cultures. The results show that the inhibition of EGF activity in Tgf
      beta3 null mouse palate cultures improves palatal shelf adhesion and fusion, with
      a particular effect on cell death, and restores the normal distribution pattern
      of Msx-1 in the palatal mesenchyme. Inhibition of TGF-beta1 does not affect
      either EGF or Msx-1 expression.

PMID- 24861082
TI  - Transplantation: CNIs to mTOR inhibitors--effects on allosensitization?

PMID- 24861081
TI  - Metabolic variation between japonica and indica rice cultivars as revealed by non
      targeted metabolomics.
AB  - Seed metabolites are critically important both for plant development and human
      nutrition; however, the natural variation in their levels remains poorly
      characterized. Here we profiled 121 metabolites in mature seeds of a wide panel
      Oryza sativa japonica and indica cultivars, revealing correlations between the
      metabolic phenotype and geographic origin of the rice seeds. Moreover, japonica
      and indica subspecies differed significantly not only in the relative abundances
      of metabolites but also in their corresponding metabolic association networks.
      These findings provide important insights into metabolic adaptation in rice
      subgroups, bridging the gap between genome and phenome, and facilitating the
      identification of genetic control of metabolic properties that can serve as a
      basis for the future improvement of rice quality via metabolic engineering. 

PMID- 24861085
TI  - Development: Fetal growth and renal outcomes.

PMID- 24861083
TI  - Pathology of IgA nephropathy.
AB  - IgA nephropathy is defined by the presence of IgA-dominant or co-dominant immune
      deposits within glomeruli. Biopsy specimens meeting these diagnostic criteria
      have a range of histological changes that are reflected in the variable clinical
      course of IgA nephropathy. The impact of histology on outcomes in IgA nephropathy
      has been clarified in a number of large retrospective clinicopathological
      studies. These studies have consistently demonstrated that the stage of disease
      at presentation, as indicated by the extent of interstitial fibrosis and tubular
      atrophy in the biopsy, is the strongest histological predictor of renal survival.
      The effect of active proliferative lesions on the disease course is less clear
      cut, owing in part to considerable treatment bias in most published retrospective
      studies. There is evidence that endocapillary hypercellularity and cellular
      crescents are responsive to immunosuppressive therapy, but this observation
      requires confirmation in prospective randomized controlled trials. Future
      challenges include improving the reproducibility of histological scoring,
      particularly for the presence and extent of endocapillary lesions, and to improve
      prognostic modelling by combining histological data with clinical variables and
      biomarker data. 

PMID- 24861086
TI  - Glomerular disease: KLF4 promotes podocyte differentiation.

PMID- 24861088
TI  - The electric double layer at a rutile TiO2 water interface modelled using density
      functional theory based molecular dynamics simulation.
AB  - A fully atomistic model of a compact electric double layer at the rutile TiO2(1 1
      0)-water interface is constructed by adding protons to bridging oxygens or
      removing them from H2O molecules adsorbed on terminal metal cation sites. The
      surface charge is compensated by F(-) or Na(+) counter ions in outer as well as
      inner sphere coordination. For each of the protonation states the energy of the
      TiO2 conduction band minimum is determined relative to the standard hydrogen
      electrode by computing the free energy for the combined insertion of an electron
      in the solid and a proton in solution away from the double layer using density
      functional theory based molecular dynamics methods. Interpreted as electrode
      potentials, this gives an estimate of the capacitance which is compared to the
      capacitance obtained from the difference in the average electrostatic potentials
      in the solid and aqueous phase. When aligned at the point of zero charge these
      two methods lead to almost identical potential-charge profiles. We find that
      inner sphere complexes have a slightly larger capacitance (0.4 F m(-2)) compared
      to outer sphere complexes (0.3 F m(-2)).

PMID- 24861087
TI  - Target of rapamycin signalling mediates the lifespan-extending effects of dietary
      restriction by essential amino acid alteration.
AB  - Dietary restriction (DR), defined as a moderate reduction in food intake short of
      malnutrition, has been shown to extend healthy lifespan in a diverse range of
      organisms, from yeast to primates. Reduced signalling through the insulin/IGF
      like (IIS) and Target of Rapamycin (TOR) signalling pathways also extend
      lifespan. InDrosophila melanogaster the lifespan benefits of DR can be reproduced
      by modulating only the essential amino acids in yeast based food. Here, we show
      that pharmacological downregulation of TOR signalling, but not reduced IIS,
      modulates the lifespan response to DR by amino acid alteration. Of the
      physiological responses flies exhibit upon DR, only increased body fat and
      decreased heat stress resistance phenotypes correlated with longevity via reduced
      TOR signalling. These data indicate that lowered dietary amino acids promote
      longevity via TOR, not by enhanced resistance to molecular damage, but through
      modified physiological conditions that favour fat accumulation. 

PMID- 24861084
TI  - Lipid biology of the podocyte--new perspectives offer new opportunities.
AB  - In the past 15 years, major advances have been made in understanding the role of
      lipids in podocyte biology. First, susceptibility to focal segmental
      glomerulosclerosis (FSGS) and glomerular disease is associated with an APOL1
      sequence variant, is expressed in podocytes and encodes apolipoprotein L1, an
      important component of HDL. Second, acid sphingomyelinase-like phosphodiesterase
      3b encoded by SMPDL3b has a role in the conversion of sphingomyelin to ceramide
      and its levels are reduced in renal biopsy samples from patients with recurrent
      FSGS. Furthermore, decreased SMPDL3b expression is associated with increased
      susceptibility of podocytes to injury after exposure to sera from these patients.
      Third, in many individuals with membranous nephropathy, autoantibodies against
      the phospholipase A2 (PLA2) receptor, which is expressed in podocytes, have been
      identified. Whether these autoantibodies affect the activity of PLA2, which
      liberates arachidonic acid from glycerophospholipids and modulates podocyte
      function, is unknown. Fourth, clinical and experimental evidence support a role
      for ATP-binding cassette sub-family A member 1-dependent cholesterol efflux, free
      fatty acids and glycerophospolipids in the pathogenesis of diabetic kidney
      disease. An improved understanding of lipid biology in podocytes might provide
      insights to develop therapeutic targets for primary and secondary
      glomerulopathies. 

PMID- 24861090
TI  - Elevated Levels of Coagulation Factor VIII in Patients With Venous Leg Ulcers.
AB  - Chronic venous disease affects millions of people around the world. Venous
      valvular incompetencies and venous reflux, often a result of outflow obstruction
      are important contributors to venous disease. The prevalence of thrombophilia is
      increased in patients with chronic venous insufficiency (CVI). The recognition of
      underlying thrombophilia particularly in young patients opens new avenues in the
      management and prevention plan. We emphasize on the consideration of workup for
      coagulopathy, especially factor VIII deficiency in young patients with venous
      disease. We report 3 patients with chronic leg ulcers and high levels of FVIII:C
      activity in plasma and other associated thrombophilic factors. We highlight the
      need to get a workup done for thrombophilia in young patients with recurrent and
      chronic leg ulcers related to venous insufficiency or livedoid vasculopathy.
      Further studies with larger sample sizes are required to define the definite
      indications for the thrombophilia workups.

PMID- 24861089
TI  - Fabrication of crystals from single metal atoms.
AB  - Metal nanocrystals offer new concepts for the design of nanodevices with a range
      of potential applications. Currently the formation of metal nanocrystals cannot
      be controlled at the level of individual atoms. Here we describe a new general
      method for the fabrication of multi-heteroatom-doped graphitic matrices decorated
      with very small, angstrom-sized, three-dimensional (3D)-metal crystals of defined
      size. We irradiate boron-rich precious-metal-encapsulated self-spreading polymer
      micelles with electrons and produce, in real time, a doped graphitic support on
      which individual osmium atoms hop and migrate to form 3D-nanocrystals, as small
      as 15 A in diameter, within 1 h. Crystal growth can be observed, quantified and
      controlled in real time. We also synthesize the first examples of mixed ruthenium
      osmium 3D-nanocrystals. This technology not only allows the production of
      angstrom-sized homo- and hetero-crystals, but also provides new experimental
      insight into the dynamics of nanocrystals and pathways for their assembly from
      single atoms.

PMID- 24861091
TI  - Angiogenic Effect of Mesenchymal Stem Cells as a Therapeutic Target for Enhancing
      Diabetic Wound Healing.
AB  - Impaired wound-healing activity in diabetes could result from several factors,
      including severely damaged angiogenic responses, which can affect wound healing
      process to cause delayed wound repair. Mesenchymal stem cells (MSCs) have been
      shown to enhance wound healing via multiple effects, including promoting
      angiogenesis both in vitro and in vivo; however, the mechanisms involved in
      enhancing diabetic wound healing are barely understood. This article reviews the
      recent literatures on MSCs treatment for promoting angiogenesis or
      vascularization in diabetic wounds and the potential mechanisms involved, with an
      emphasis on the role of paracrine soluble factors. Meanwhile, the potential
      benefits and related risks associated with the therapeutic use of MSCs have been
      presented and may lead to better understanding of the influence of MSCs without
      increasing potential risks. Further investigation will be required to determine
      the molecular basis of paracrine mechanisms and regulated angiogenesis of MSCs
      for its rational manipulation for impaired angiogenesis repair and diabetic wound
      healing.

PMID- 24861092
TI  - Sulodexide as Adjunctive Therapy in Diabetic Foot Patients With Critical Limb
      Ischemia Treated With Percutaneous Transluminal Angioplasty.
AB  - We evaluated the safety and efficacy of sulodexide, a biocompound of glycosamin
      glicans, as adjunct medical therapy to percutaneous transluminal angioplasty
      (PTA) in diabetes mellitus (DM) patients with critical limb ischemia (CLI). We
      studied 27 consecutive DM patients with CLI successfully subjected to PTA who, on
      top of standard antiplatelet therapy, received sulodexide 25 mg bid, and were
      followed-up for 24 weeks, monitoring adverse events, transcutaneous oxygen
      tension (TcPO2), ankle-brachial pressure index, pain, and ulcer dimension. At the
      end of follow-up, ulcer healing, amputation rates, and cardiovascular risk
      profile of patients were evaluated. Patients were compared with a historical
      superimposable control group that was treated for the same indications in the
      same way as the study group, except for sulodexide inception. No differences in
      ulcer healing and amputation rates were found at the end of follow-up between the
      groups. In the study group, TcPO2 was significantly (P < .05) higher at the end
      of follow-up, and pain intensity was reduced more rapidly. Plasma fibrinogen and
      plasma creatinine concentration were significantly (P < .05) reduced in study
      group at the end of follow-up. No differences in adverse events were observed
      between the groups during follow-up. Our data suggest that sulodexide
      administration after PTA, on top of antiplatelet therapy, may improve the outcome
      of PTA in DM patients with CLI by improving microcirculatory function.

PMID- 24861093
TI  - Baropodometric Evaluations and Sensitivity Alterations in Plantar Ulcer Formation
      in Leprosy.
AB  - Leprosy is a chronically evolving granulomatous disease caused by the bacillus
      Mycobacterium leprae, which exhibits tropism for peripheral and motor nerves and
      slow-growing inflammation that affects the peripheral nervous system, especially
      the sensory fibers. The aim of this study was to observe the relationship between
      peak pressure and abnormal sensitivity for the formation of plantar ulcers in
      patients with multibacillary (MB) and paucibacillary (PB) leprosy. A total of 51
      individuals with leprosy were evaluated and classified as either MB or PB and
      then submitted to the Semmes-Weinstein sensitivity test; 20 normal individuals
      were examined as a control group and took a baropodometric test. The pressure
      peaks and sensitivity alterations were noted and compared within groups. Leprosy
      patients exhibited a greater loss of sensitivity at the heel area that might
      compromise gait. During dynamic analysis, the MB group with altered sensitivity
      for right and left feet and PB (left feet) group showed the highest plantar
      pressure values. Skin damage (calluses or ulcers) did not occur within the areas
      of high plantar pressure in 80% of MB patients, whereas skin damage was observed
      in 38% of PB patients in the areas of higher peak pressures. According to these
      findings, baropodometry and sensitivity tests play an important role in the
      understanding of ulcer biodynamics. In addition, it could be inferred that the
      loss of protective sensibility in MB patients is predictive of plantar ulcers,
      whereas plantar pressure peaks seem to be of greater importance in PB patients.

PMID- 24861094
TI  - Maggot Therapy for Elephantiasis Nostras Verrucosa Reveals New Applications and
      New Complications: A Case Report.
AB  - Elephantiasis nostras verrucosa (ENV) is a rare dermatologic condition caused by
      chronic nonfilarial lymphedema. The treatment for ENV is challenging and based
      solely on case reports. We report novel therapy for ENV with maggot debridement
      therapy (MDT), an effective wound therapy that has gained popularity with the
      rise of antimicrobial resistance. MDT, in combination with tangential surgical
      debridement, was effective in the treatment of ENV. In nature, sheep infested
      with more than 16 000 blow fly larvae exhibit ammonia toxicity. Although
      hyperammonemia as a side effect of maggot therapy has been theorized, its
      existence has not been described in human studies until this case. This patient
      exhibited hyperammonemia during maggot therapy; with alterations in serum ammonia
      reflecting changes in larval population. Maggot therapy should be considered for
      the treatment of ENV. Hyperammonemia with maggot therapy exists, and clinicians
      who employ this treatment should be aware of this potential adverse effect.

PMID- 24861095
TI  - Quantitative Evaluation of Maceration in Venous Leg Ulcers by Transepidermal
      Water Loss (TEWL) Measurement.
AB  - Skin maceration is a clinical manifestation in venous leg ulcers that leads to
      severe consequences for patients' quality of life and wound management. The aim
      of this study was to explore the use of transepidermal water loss (TEWL)
      measurement technique to quantify different level of surrounding skin maceration
      in patients with venous leg ulcers. A total of 50 patients were recruited and
      TEWL measurements were taken with a portable device on different locations
      surrounding the leg ulcer and on control skin. A clinical score for maceration
      was used and correlated to the involvement of surrounding skin. Statistically
      significant differences of TEWL values were noted between affected skin and
      control site (P < .001). Statistics showed an increase in TEWL values as the
      maceration clinical score increased (r = 0.954). Objective monitoring of skin
      maceration in venous leg ulcer with TEWL measurement represents an useful tool to
      analyze morphologic changes at different time points during treatment.

PMID- 24861096
TI  - Differential Expression of Matrix Metalloproteinase-9 Gene in Wounds of Type 2
      Diabetes Mellitus Cases With Susceptible -1562C>T Genotypes and Wound Severity.
AB  - Coordinated extracellular matrix deposition is a prerequisite for proper wound
      healing which is mainly orchestrated by matrix metalloproteinases (MMPs).
      Diabetic wounds generally show compromised wound healing cascade and abnormal
      MMP9 concentration is one of the cause. Our group have recently shown that the
      polymorphism -1562 C>T in the promoter region of MMP9 gene is associated with
      pathogenesis of wound healing impairment in T2DM patients. In present study we
      have done expression profiling of MMP9 gene in the wound biopsy of DFU cases.
      Expression level of MMP9 mRNA was then compared with susceptible -1562 C>T
      genotypes (TT and CT) as well as with different grades of wounds. We also
      screened the promoter region of MMP9 gene to see the methylation state of CpGs
      present there. Our study suggests that levels of MMP9 mRNA increase significantly
      with the wound grades. Moreover, the MMP9 levels in diabetic wounds were also
      dependent on -1562 C>T polymorphism in the promoter region of MMP9. Diabetic
      wounds also showed a significant unmethylated status of MMP9 promoter compared to
      control wounds. In conclusion, The risk genotypes of -1562 C>T polymorphism along
      with lack of methylation of CpG sites in MMP9 gene promoter may result in altered
      expression of MMP9 in wounds of T2DM cases resulting into nonhealing chronic
      ulcers in them.

PMID- 24861097
TI  - Hypermobility syndromes from the clinician's perspective: an overview.
AB  - Symptomatic generalized hypermobility is a frequent occurring condition among
      patients referred to the rheumatologist or other medical specialist. In a subset
      of patients, a further classifying diagnosis of a specific syndrome can (and
      should) be made, based on pattern recognition and knowledge of the spectrum of
      hypermobility syndromes. Diagnostic clues are the patient's and family history
      and signs at physical examination, including skin abnormalities. It is especially
      important to recognize hypermobility syndromes with potentially life threatening
      complications. Genetic testing is only available for some syndromes; is only
      indicated if there is a reasonable pretest probability regarding a specific
      syndrome, especially if this syndrome can have life-threatening complications.
      The therapy is for the major part of syndromes only symptomatic; key features of
      management are education and physical exercises; joint surgery is to be avoided. 

PMID- 24861098
TI  - Associations between physical activity and sedentary time on components of
      metabolic syndrome among adults with HIV.
AB  - Recent data show that people living with HIV/AIDS (PLWHA) are at a greater risk
      of cardiovascular disease (CVD), which could possibly be explained by an
      increased prevalence of metabolic syndrome (MetSyn) due to the known toxicities
      associated with antiretroviral therapy (ART). The purpose of this study is to
      examine the relationships between physical activity (PA) and components of MetSyn
      in a sample of PLWHA taking ART. A total of 31 males and 32 females living with
      HIV and currently taking ART were enrolled in a home-based PA intervention aimed
      to reduce risk factors for CVD. Clinical assessments included measures of resting
      blood pressure (BP), waist circumference, height, weight, PA levels via
      accelerometer, and a fasted blood draw. Components of MetSyn were divided into
      three clusters (1 = 0-1; 2 = 2; 3 = 3 or more). A one-way analysis of variance
      was used to determine differences between clusters. Multiple linear regressions
      were used to identify significant associations between moderate intensity PA
      (MPA) and sedentary time among components of MetSyn. MPA was significantly lower
      across MetSyn clusters (p < 0.001), whereas sedentary time was significantly
      higher (p = 0.01). A multiple linear regression showed MPA to be a significant
      predictor of waist circumference after controlling for age, race, gender, and
      sedentary time. Routine PA can be beneficial in helping PLWHA reduce waist
      circumference ultimately leading to metabolic improvements. This in turn would
      help PLWHA self-manage known components of MetSyn, thus reducing their risk of
      CVD and mortality. 

PMID- 24861100
TI  - Screening for hepatitis B virus infection: a public health imperative.

PMID- 24861099
TI  - Green tea catechins and blood pressure: a systematic review and meta-analysis of
      randomised controlled trials.
AB  - PURPOSE: Although previous literature has reported that regular green tea
      consumption may improve blood pressure, the evidence from these studies is not
      consistent. The present study systematically reviewed randomised controlled
      trials and examined the effect of green tea consumption on blood pressure using
      meta-analysis. METHODS: Search of ProQuest, PubMed, Scopus and Cochrane Library
      (CENTERAL) was conducted, to identify eligible articles. Articles from 1995 to
      2013 were included. A random-effect model was chosen to calculate the effect of
      combined trials. RESULT: Thirteen studies were included in the meta-analysis.
      Green tea consumption significantly changed systolic blood pressure, by -2.08 mm
      Hg (95% CI -3.06, -1.05), and diastolic blood pressure, by -1.71 mm Hg (95% CI 
      2.86, -0.56), compared to the control. Changes in lipid profile, blood glucose
      and body mass index were also assessed in the meta-analysis. A significant
      reduction was found in total cholesterol (-0.15 mmol/L [95% CI -0.27, -0.02]) and
      low-density lipoprotein cholesterol (-0.16 mmol/L [95% CI -0.22, -0.09]). Changes
      in other parameters did not reach statistical significance. Subgroup analysis
      suggested a greater reduction in both systolic and diastolic blood pressure in
      studies that included participants with a baseline mean systolic blood pressure
      of >= 130 mm Hg, and studies involving consuming green tea as an extract.
      CONCLUSION: The present meta-analysis suggests that green tea and its catechins
      may improve blood pressure, and the effect may be greater in those with systolic
      blood pressure >= 130 mm Hg. The meta-analysis also suggests that green tea
      catechins may improve total and low-density lipoprotein cholesterol.

PMID- 24861102
TI  - Identification and validation of quantitative trait loci for seed yield, oil and
      protein contents in two recombinant inbred line populations of soybean.
AB  - Soybean seeds contain high levels of oil and protein, and are the important
      sources of vegetable oil and plant protein for human consumption and livestock
      feed. Increased seed yield, oil and protein contents are the main objectives of
      soybean breeding. The objectives of this study were to identify and validate
      quantitative trait loci (QTLs) associated with seed yield, oil and protein
      contents in two recombinant inbred line populations, and to evaluate the
      consistency of QTLs across different environments, studies and genetic
      backgrounds. Both the mapping population (SD02-4-59 * A02-381100) and validation
      population (SD02-911 * SD00-1501) were phenotyped for the three traits in
      multiple environments. Genetic analysis indicated that oil and protein contents
      showed high heritabilities while yield exhibited a lower heritability in both
      populations. Based on a linkage map constructed previously with the mapping
      population and using composite interval mapping and/or interval mapping analysis,
      12 QTLs for seed yield, 16 QTLs for oil content and 11 QTLs for protein content
      were consistently detected in multiple environments and/or the average data over
      all environments. Of the QTLs detected in the mapping population, five QTLs for
      seed yield, eight QTLs for oil content and five QTLs for protein content were
      confirmed in the validation population by single marker analysis in at least one
      environment and the average data and by ANOVA over all environments. Eight of
      these validated QTLs were newly identified. Compared with the other studies,
      seven QTLs for seed yield, eight QTLs for oil content and nine QTLs for protein
      content further verified the previously reported QTLs. These QTLs will be useful
      for breeding higher yield and better quality cultivars, and help effectively and
      efficiently improve yield potential and nutritional quality in soybean. 

PMID- 24861101
TI  - Homeologous genes involved in mannitol synthesis reveal unequal contributions in
      response to abiotic stress in Coffea arabica.
AB  - Polyploid plants can exhibit transcriptional modulation in homeologous genes in
      response to abiotic stresses. Coffea arabica, an allotetraploid, accounts for 75%
      of the world's coffee production. Extreme temperatures, salinity and drought
      limit crop productivity, which includes coffee plants. Mannitol is known to be
      involved in abiotic stress tolerance in higher plants. This study aimed to
      investigate the transcriptional responses of genes involved in mannitol
      biosynthesis and catabolism in C. arabica leaves under water deficit, salt stress
      and high temperature. Mannitol concentration was significantly increased in
      leaves of plants under drought and salinity, but reduced by heat stress. Fructose
      content followed the level of mannitol only in heat-stressed plants, suggesting
      the partitioning of the former into other metabolites during drought and salt
      stress conditions. Transcripts of the key enzymes involved in mannitol
      biosynthesis, CaM6PR, CaPMI and CaMTD, were modulated in distinct ways depending
      on the abiotic stress. Our data suggest that changes in mannitol accumulation
      during drought and salt stress in leaves of C. arabica are due, at least in part,
      to the increased expression of the key genes involved in mannitol biosynthesis.
      In addition, the homeologs of the Coffea canephora subgenome did not present the
      same pattern of overall transcriptional response, indicating differential
      regulation of these genes by the same stimulus. In this way, this study adds new
      information on the differential expression of C. arabica homeologous genes under
      adverse environmental conditions showing that abiotic stresses can influence the
      homeologous gene regulation pattern, in this case, mainly on those involved in
      mannitol pathway.

PMID- 24861103
TI  - Perception of emotional nonsense sentences in China, Egypt, Estonia, Finland,
      Russia, Sweden, and the USA.
AB  - The present study focused on the identification of emotions in cross-cultural
      conditions on different continents and among subjects with divergent language
      backgrounds. The aim was to investigate whether the perception of the basic
      emotions from nonsense vocal samples was universal, dependent on voice quality,
      musicality, and/or gender. Listening tests for 350 participants were conducted on
      location in a variety of cultures: China, Egypt, Estonia, Finland, Russia,
      Sweden, and the USA. The results suggested that the voice quality parameters
      played a role in the identification of emotions without the linguistic content.
      Cultural background may affect the interpretation of the emotions more than the
      presumed universality. Musical interest tended to facilitate emotion
      identification. No gender differences were found. 

PMID- 24861104
TI  - On the accuracy of adults' auditory perception of normophonic and dysphonic
      children's personality.
AB  - We investigated the accuracy of auditory inferences of personality of Belgian
      children with vocal fold nodules (VFN). External judges (n = 57) were asked to
      infer the personality of normophonic (NP) children and children with VFN (n = 10)
      on the basis of vowels and sentences. The auditory inferred profiles were
      compared to the actual personality of NP and VFN children. Positive and partly
      accurate inferences of VFN children's personality were made on the basis of
      connected speech, while sustained vowels yielded negative and inaccurate
      inferences of personality traits of children with VFN. Dysphonic voice quality,
      as defined by the overall severity of vocal abnormality, conveyed inaccurate and
      low degrees of extraversion. This effect was counterbalanced in connected speech
      by faster speaking rate that accurately conveyed higher degrees of extraversion,
      a characteristic trait of VFN children's actual personality. 

PMID- 24861106
TI  - Dissociation: adjustment or distress? Dissociative phenomena, absorption and
      quality of life among Israeli women who practice channeling compared to women
      with similar traumatic history.
AB  - This study aimed to explore the relationship between traumatic history,
      dissociative phenomena, absorption and quality of life among a population of
      channelers, in comparison with a population of non-channelers with similar
      traumatic history. The study sample included 150 women. The measures included
      Traumatic Experiences Scale, Dissociative Experience Scale, Absorption Scale,
      Brief Symptom Inventory and Quality of Life (QOL) Assessment. Channelers
      presented significantly higher levels of dissociation, absorption and
      psychological health compared to the other group. Dissociation and absorption
      were trauma-related only among the comparison group. Hence, dissociation has
      different qualities among different people, and spiritual practice contributes to
      QOL. 

PMID- 24861105
TI  - Evolutionary and functional novelty of pancreatic ribonuclease: a study of
      Musteloidea (order Carnivora).
AB  - Pancreatic ribonuclease (RNASE1) is a digestive enzyme that has been one of the
      key models in studies of evolutionary innovation and functional diversification.
      It has been believed that the RNASE1 gene duplications are correlated with the
      plant-feeding adaptation of foregut-fermenting herbivores. Here, we characterized
      RNASE1 genes from Caniformia, which has a simple digestive system and lacks
      microbial digestion typical of herbivores, in an unprecedented scope based on
      both gene sequence and tissue expression analyses. Remarkably, the results
      yielded new hypotheses regarding the evolution and the function of Caniformia
      RNASE1 genes. Four independent gene duplication events in the families of
      superfamily Musteloidea, including Procyonidae, Ailuridae, Mephitidae and
      Mustelidae, were recovered, rejecting previous Mustelidae-specific duplication
      hypothesis, but supporting Musteloidea duplication hypothesis. Moreover, our
      analyses revealed pronounced differences among the RNASE1 gene copies regarding
      their selection pressures, pI values and tissue expression patterns, suggesting
      the differences in their physiological functions. Notably, the expression
      analyses detected the transcription of a RNASE1 pseudogene in several tissues,
      raising the possibility that pseudogenes are also a potential source during the
      RNase functional diversification. In sum, the present work demonstrated a far
      more complex and intriguing evolutionary pattern and functional diversity of
      mammalian ribonuclease than previously thought. 

PMID- 24861108
TI  - [Survival of patients with biopsy-proven idiopathic pulmonary fibrosis: Chilean
      National Thorax Institute experience].
AB  - BACKGROUND: Idiopathic Pulmonary Fibrosis (IPF) is the most prevalent of all
      interstitial lung diseases. The usual underlying pathological picture is an
      interstitial pneumonia (UIP). AIM: To describe the evolution of a Chilean cohort
      of patients with IPF. MATERIAL AND METHODS: Patients with the disease were
      identified at the pathology registry of National Institute of Thoracic Diseases,
      Santiago, Chile. Patients were included if they had surgical biopsy of UIP and
      compatible clinical and radiological characteristics. The medical records of
      included patients were reviewed, recording clinical information and lung function
      test results. Survival was analyzed obtaining death records from the Chilean
      National Identification Service. RESULTS: Data from 142 patients with a mean age
      of 58 years (42% men), were analyzed. Mean initial lung function showed a forced
      vital capacity (FVC) of 73%, carbon monoxide diffusing capacity (DLCO) of 57% and
      a distance covered in 6-minute walk (6MWT) of 95% of expected normal values. The
      median survival was 80 months. Predictors of survival were a DLCO of less than
      40% and an oxygen saturation at the end of the 6MWT of less than 89%.
      CONCLUSIONS: Survival in this group of patients was higher than the figures
      reported elsewhere. DLCO and the fall of oxygen saturation after walking were
      predictors of mortality, as previously described in other populations.

PMID- 24861109
TI  - [Prevalence of endometriosis in 287 women undergoing surgical sterilization in
      Santiago Chile].
AB  - BACKGROUND: The clinical manifestations of endometriosis are infertility,
      dysmenorrhea, sexuality disturbances, and chronic pelvic pain. It is the cause of
      30 to 50% of infertility cases. In developed countries, the prevalence of
      endometriosis among women undergoing surgical sterilization is approximately 6%.
      AIM: To determine the prevalence of endometriosis among women with proven
      fertility in Santiago de Chile. MATERIAL AND METHODS: Review of surgical
      protocols of 287 women aged 25 to 49 years, subjected to a surgical sterilization
      between 2007 and 2011. RESULTS: Endometriosis was found in 14 of the 287 women
      (4.9%). In spite of being asymptomatic, five of the 14 women with endometriosis
      were classified as severe, due to the presence of at least one endometrioma. In
      order of frequency, the most commonly affected anatomical sites were the ovary,
      the peritoneum, the posterior cul-de-sac and uterosacral ligaments. CONCLUSIONS:
      Our findings are very similar to those found elsewhere and suggest that fertile
      women could better tolerate endometriosis than their infertile counterparts.

PMID- 24861110
TI  - [Effects of vitamin C administration on cholesterol gallstone formation].
AB  - BACKGROUND: Biliary cholesterol is transported by vesicles and micelles.
      Cholesterol microcrystals are derived from thermodynamically unstable vesicles.
      In experimental animals vitamin C deficiency leads to a super-saturation of
      biliary cholesterol and to the formation of gallstones. AIM: To search for a
      possible relationship between serum levels of vitamin C and the formation of
      cholesterol gallstones in patients with cholelithiasis. MATERIAL AND METHODS:
      Thirteen patients with cholelithiasis and a programmed surgical intervention were
      treated with 2 g/day of vitamin C per os for two weeks before surgery. Forty nine
      patients subjected to a cholecystectomy not supplemented with vitamin C were
      studied as controls. Plasma concentrations of vitamin C and lipid profiles were
      measured. The cholesterol saturation index, crystallization time, cholesterol and
      phospholipid content in vesicles and micelles, separated by gel filtration
      chromatography, were studied in bile samples obtained from the gallbladder.
      RESULTS: Vitamin C supplementation did not change significantly plasma lipids and
      bile lipid concentrations. However, in supplemented patients, significant
      reductions in vesicular cholesterol content (6.5 +/- 4.8% compared to 17.9 +/-
      14.0% in the control group; p < 0.05) and vesicular cholesterol/phospholipid
      ratio (0.71 +/- 0.53 compared to 1.36 +/- 1.15 in controls; p < 0.05), were
      observed. CONCLUSIONS: Vitamin C administration may modify bile cholesterol
      crystallization process, the first step in cholesterol gallstone formation.

PMID- 24861111
TI  - [Psychosocial determinants of organ donation among Chilean university students].
AB  - BACKGROUND: Organ donation (OD) is a complex process that among other factors,
      depends on the consent of the potential donor's family. Previous evidences have
      shown that the intention of a behavior predicts that behavior in the future. AIM:
      To study the effect of believes, worries, knowledge and attitudes on the
      intention of OD after own death as well as OD of a deceased relative. MATERIAL
      AND METHODS: A total of 3,297 Chilean university students responded to a survey
      about the intention to donate organs through a web link. We conducted a path
      analysis and a structural equation technique was used. The model explained more
      than 50% of the variance of the dependent variables. RESULTS: The intention of
      respondents to donate their own organs or those of family members after death
      were predicted by attitude toward OD, social influences and family discussion.
      Attitude was the main predictor of the model, which is determined by the negative
      effect of bodily apprehensions and the positive effect of knowledge about brain
      death. CONCLUSIONS: Attitude, knowledge and concerns are the main determinants of
      donation intention. The results prove the validity of the Theory of Reasoned
      Action as a theoretical model to explain the intentions of OD.

PMID- 24861112
TI  - [High intensity interval training improves glycemic control and aerobic capacity
      in glucose intolerant patients].
AB  - BACKGROUND: Proper exercise training modifies intra miocellular energy
      utilization, glucose transport and mitochondrial biogenesis. AIM: To determine
      the therapeutic effects of a high intensity intermittent training (HIIT) program
      on glucose homeostasis, physical fitness and body fat in glucose intolerant
      patients. PATIENTS AND METHODS: Eighteen patients with overweight or obesity and
      glucose intolerance were invited to participate in an exercise program consisting
      in three sessions per week for 3 months. Ten participants aged 35 +/- 13 years
      who attended > 26 of the planned 36 sessions, were considered as adherent to
      exercise. The other eight participants aged 37 +/- 17 years, who attended to a
      mean of 13 sessions, were considered as non-adherent. Both groups had similar
      body weight, body mass index, body fat, plasma glucose 2 h after an oral glucose
      load and maximal oxygen uptake. All these variables were measured at the end of
      exercise intervention. Each session consisted of 1 min exercise of cycling at
      maximal intensity until muscle fatigue followed by 2 min rest, repeated 10 times.
      RESULTS: Among adherent participants, twelve weeks of HIIT improved significantly
      maximal oxygen uptake (6.1 + 3.6 mL/kg/min or 24.6%), reduced 2 h post load blood
      glucose (-33.7 + 47.9 mg/dL or -12.5%) and body fat (-4.3 + 5.6 kg). No
      significant changes were observed in the non-adherent group. CONCLUSIONS: HIIT
      exercise reduces blood glucose after an oral load in glucose intolerant patients.

PMID- 24861113
TI  - [Monitoring medication errors in an internal medicine service].
AB  - BACKGROUND: Patients admitted to internal medicine services receive multiple
      drugs and thus are at risk of medication errors. AIM: To determine the frequency
      of medication errors (ME) among patients admitted to an internal medicine service
      of a high complexity hospital. MATERIAL AND METHODS: A prospective observational
      study conducted in 225 patients admitted to an internal medicine service. Each
      stage of drug utilization system (prescription, transcription, dispensing,
      preparation and administration) was directly observed by trained pharmacists not
      related to hospital staff during three months. ME were described and categorized
      according to the National Coordinating Council for Medication Error Reporting and
      Prevention. In each stage of medication use, the frequency of ME and their
      characteristics were determined. RESULTS: A total of 454 drugs were prescribed to
      the studied patients. In 138 (30,4%) indications, at least one ME occurred,
      involving 67 (29,8%) patients. Twenty four percent of detected ME occurred during
      administration, mainly due to wrong time schedules. Anticoagulants were the
      therapeutic group with the highest occurrence of ME. CONCLUSIONS: At least one ME
      occurred in approximately one third of patients studied, especially during the
      administration stage. These errors could affect the medication safety and avoid
      achieving therapeutic goals. Strategies to improve the quality and safe use of
      medications can be implemented using this information.

PMID- 24861114
TI  - [Information disclosure and decision making preferences of patients with advanced
      cancer in a Pain and Palliative Care Unit in Chile].
AB  - Information disclosure and decision making process are important steps in
      advanced cancer patients management; however, there is no research done in this
      area in Chile. AIMS: To know the preferences of patients with advanced cancer
      related to information disclosure and style of decision making process. METHODS:
      Prospective observational study with patients in the Palliative Care Unit of
      Sotero del Rio Hospital, in Santiago, Chile. The preferences were evaluated with
      a Disclosure Information and a Decision Making Preferences Questionnaire.
      RESULTS: 100 patients were recruited, 52% males, average age 63 years; 90% wanted
      to receive complete information about diagnosis and 89% complete information
      about prognosis. The preferences related to decision making process style were:
      60% shared, 27% passive and 13% active. The expressed satisfaction with the
      information received was 89% and 87% with the way decisions were actually made.
      CONCLUSIONS: A majority of patients preferred to receive complete information
      about diagnosis and prognosis and to make shared decisions. The satisfaction with
      information disclosure and decision making process was very high. The data of
      this study supports the need of an adequate information disclosure and of
      exploring the individual preferences of our patients, with the goal of promoting
      an informed decision making process that respects the preferences of our
      patients.

PMID- 24861115
TI  - [BRAF gene mutation in wild-type KRAS patients with colorectal cancers].
AB  - BACKGROUND: In colorectal cancer, BRAF and KRAS mutation are mutually exclusive,
      but both are independent prognostic factors for the disease. AIM: To determine
      the frequency of BRAF V600E mutation in colorectal cancer. MATERIAL AND METHODS:
      A KRAS mutation study was carried out in 100 tissue samples of primary and
      metastatic adenocarcinomas of colon and rectum from patients aged 61.1 +/- 62
      years (56 women). Negative KRAS mutation cases underwent study of BRAF V600E
      mutation by restriction fragment length polymorphism (RFLP) and direct
      sequencing. RESULTS: Primary tumors were located in the colon and rectum in 88
      and six cases respectively. Five were liver metastases and in one case, the
      sample location was undetermined. Forty two samples were KRAS positive (mutated).
      In 12 of the 58 KRAS negative (wild type) samples, the V600E mutation in codon 15
      of the BRAF gene was demonstrated. No differences in the frequency and
      distribution of mutations, stratified by gender, age, primary tumor versus
      metastasis, or tumor location were observed. CONCLUSIONS: Twelve percent of KRAS
      negative colorectal cancer samples showed BRAF gene mutation. Considering that
      42% of samples have a KRAS mutation, 54% of patients should not respond to
      therapies with monoclonal antibodies directed against epidermic growth factor
      (EGFR) pathway.

PMID- 24861116
TI  - [Mineralocorticoid receptor antagonists and therapeutic strategies of
      cardiovascular damage].
AB  - In recent years, much attention has focused on the role of aldosterone and
      mineralocorticoid receptors (MRs) in the pathophysiology of hypertension and
      cardiovascular disease. Patients with primary aldosteronism, in whom angiotensin
      II levels are low, have a higher incidence of cardiovascular complications than
      patients with essential hypertension. The Randomized Aldactone Evaluation Study
      (RALES) demonstrated that adding a non-specific MR antagonist, spironolactone, to
      a standard therapy that included angiotensin-converting enzyme (ACE) inhibitors,
      loop diuretics, and digoxin, significantly reduced morbidity and mortality in
      patients with moderate to severe heart failure. Similarly, the Eplerenone Post
      Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS)
      showed that the addition of a selective MR antagonist (ARM), eplerenone, to an
      optimal medical therapy reduces morbidity and mortality among patients with acute
      myocardial infarction complicated by left ventricular dysfunction and heart
      failure. These data suggest that aldosterone induces cardiac injury through
      activation of MRs and support the notion that MR blockade has beneficial effects
      on aldosterone-dependent cardiac injury, through mechanisms that cannot be simply
      explained by hemodynamic changes. Although, MRA are highly effective in patients
      with heart failure, the risk of hyperkalemia should not be overlooked. Serious
      hyperkalemia events were reported in some MRA clinical trials; however these
      risks can be mitigated through appropriate patient selection, dose selection,
      patient education, monitoring, and follow-up. 

PMID- 24861117
TI  - [The paradox of being physically active but sedentary or sedentary but physically
      active].
AB  - The use of objective methods to measure physical activity and thus assess
      sedentary lifestyle, may change the definition of individuals as being sedentary
      or physically active. This situation would also interfere on the benefits of
      physical activity and the dangerous effects of sedentary lifestyle on health. The
      aim of this review is to clarify the changes that have recently occurred in this
      area. These could be included in future health care strategies and
      recommendations for the population. 

PMID- 24861118
TI  - [The relevance of the International Committee of Medical Journal Editors (ICMJE)
      for medical publishing and research].
AB  - The International Committee of Medical Journal Editors is a leading independent
      institution providing guidance for the report of biomedical research and health
      related topics in medical journals. Established in 1978, it is currently
      constituted by editors of fourteen general medical journals from different
      countries, plus one representative for the US National Library of Medicine and
      one representative for the World Association of Biomedical Journal Editors. Since
      1978 the Committee provides a document, originally named "Uniform
      Requirements...", "to help authors, editors, and others involved in peer review
      and biomedical publishing create and distribute accurate, clear, unbiased medical
      journal articles". This document has been updated several times and the last
      version was released in August 2013, now renamed "Recommendations for the
      Conduct, Reporting, Editing, and Publication of Scholarly Work in Medical
      Journals", available in www.icmje.org and citable as "ICMJE Recommendations". A
      vast proportion of medical journals, worldwide, have adopted these
      recommendations as rules. The ICMJE discusses and provides guidance on several
      relevant aspects including criteria on authorship, peer review, scientific
      misconduct, conflicts of interest, clinical trials registration, good editorial
      practices, the relations between editors and journal owners, the protection of
      individuals subject to medical research, the solvency of electronic publications,
      among others. The 2013 ICMJE Annual Meeting took place in Santiago, Chile, in
      November 4 and 5. The photograph shows attendants to the final session. 

PMID- 24861119
TI  - [The infantile sexual seduction: revolution and aftermath of Freud's theory].
AB  - There is no question about the negative effects of child sexual abuse. Freud's
      seduction theory asserts that psychoneuroses in adults are caused by reactivation
      of forgotten recollections of gross sexual abuse (involving the genitals) that
      had taken place prior to the age of 8 to 10 years. His contribution consisted in
      the discovery of specific events, prior to puberty, which were indispensable to
      the formation of psychoneuroses. If an adult patient recalled an infantile sexual
      experience, Freud assumed the interference of a pervert: a child was sexually
      innocent unless it had been traumatized. But Freud's technique of clinical
      exploration had not attained adequate reliability and was not immune to
      prejudices. Freud himself dropped his mechanical, static theory that presupposed
      a single type of accidentally occurring trauma prior to puberty, allowing him to
      develop his new drive and fantasy theory. 

PMID- 24861120
TI  - [Development of a professional social responsibility questionnaire for
      physicians].
AB  - BACKGROUND: Professional Social Responsibility is now imperative for the practice
      of medicine. However, there are no instruments to assess it among physicians.
      AIM: To construct and evaluate the factorial structure and reliability of a
      questionnaire designed to measure socially responsible behavior in physicians.
      MATERIAL AND METHODS: The Questionnaire on Medical Socially Responsible Behavior,
      consisting of 34 items, was constructed. It was applied to 284 physicians and
      medical students. After eliminating respondents who omitted questions, a valid
      sample of 214 individuals aged 23 to 67 years (51.4% males) was obtained. We
      assessed the factorial structure, reliability, discriminative ability of the
      items and correlation between factors. RESULTS: Exploratory factorial analysis,
      conducted using the principal axis method, identified the presence of three
      factors and considered 30 items. The reliability of the factors, assessed using
      Cronbach's alpha, ranged from 0.73 to 0.89. Only one item had a low correlation
      of 0.3. Correlations between the three factors were direct and high. CONCLUSIONS:
      The developed questionnaire presents a definite factorial structure, with
      internally consistent and correlated factors and with adequate psychometric
      properties.

PMID- 24861121
TI  - [Clinical practice guidelines development and implementation: an introduction].
AB  - Clinical Practice Guidelines (CPG), defined as "statements that include
      recommendations intended to optimize patient care that are informed by a
      systematic review of evidence and an assessment of the benefits and harms of
      alternative care options", are tools currently present in every level of our
      health system. This article introduces guidelines development and implementation
      processes and it reviews the Chilean experience. The main stages in a CPG
      development are question formulation, search and analysis of the existing
      evidence related to those questions, and making judgments about that evidence in
      order to formulate recommendations for clinical practice. At the national level,
      guidelines development processes are conducted by the Ministry of Health, and
      even when recent evaluations show some good results, there are a number of
      aspects - such as applicability - that should be improved. On the other hand, CPG
      should be implemented using effective strategies in order to obtain changes in
      clinical practice and patients' outcomes. The existing evidence about the effects
      of the different implementation strategies shows modest and highly variable
      results. At the national level, there is a dearth of research about the design
      and evaluation of implementation strategies, and most of it has been focused in
      the evaluation of adherence to specific recommendations. 

PMID- 24861122
TI  - [Critically appraised article: The quality of clinical practice guidelines over
      the last two decades: a systematic review of guidelines appraisal studies].
AB  - BACKGROUND: Despite the increasing number of manuals on how to develop clinical
      practice guidelines (CPGs) there remain concerns about their quality. The aim of
      this study was to review the quality of CPGs across a wide range of healthcare
      topics published since 1980. METHODS: The authors conducted a literature search
      in MEDLINE to identify publications assessing the quality of CPGs with the
      Appraisal of Guidelines, Research and Evaluation (AGREE) instrument. For the
      included guidelines in each study, the authors gathered data about the year of
      publication, institution, country, healthcare topic, AGREE score per domain and
      overall assessment. RESULTS: In total, 42 studies were selected, including a
      total of 626 guidelines, published between 1980 and 2007, with a median of 25
      CPGs. The mean scores were acceptable for the domain 'Scope and purpose' (64%;
      95% CI 61.9 to 66.4) and 'Clarity and presentation' (60%; 95% CI 57.9 to 61.9),
      moderate for domain 'Rigour of development' (43%; 95% CI 41.0 to 45.2), and low
      for the other domains ('Stakeholder involvement' 35%; 95% CI 33.9 to 37.5,
      'Editorial independence' 30%; 95% CI 27.9 to 32.3, and 'Applicability' 22%; 95%
      CI 20.4 to 23.9). From those guidelines that included an overall assessment, 62%
      (168/270) were recommended or recommended with provisos. There was a significant
      improvement over time for all domains, except for 'Editorial independence'.
      CONCLUSIONS: This review shows that despite some increase in quality of CPGs over
      time, the quality scores as measured with the AGREE Instrument have remained
      moderate to low over the last two decades. This finding urges guideline
      developers to continue improving the quality of their products. International
      collaboration could help increasing the efficiency of the process.

PMID- 24861123
TI  - [Crigler-Najjar syndrome. Report of one case with a long term follow up].
AB  - Crigler-Najjar Syndrome is an uncommon genetic disorder characterized by the
      elevation of unconjugated plasmatic bilirubin secondary to deficiency of the
      enzyme uridine diphosphate glucuronyltransferase (UDP-GT). We report a 19-years
      old woman with the syndrome diagnosed during the neonatal period, when she
      developed a severe jaundice in the first 10 days of life, reaching unconjugated
      bilirubin levels of 29 mg/dl, with normal liver function tests. After transient
      response to phototherapy, the patient was referred to a tertiary medical center
      in which an extensive work up ruled out other etiologies and the diagnosis of
      type I Crigler-Najjar syndrome was established. Currently, the patient has a mild
      mental retardation. She is receiving homemade phototherapy 18 h per day with
      acceptable control of bilirubin levels. Many mutations have been associated with
      UDP-GT dysfunction resulting in a broad spectrum of the disease. When bilirubin
      rises above physiological limits, it permeates the hematoencephalic barrier,
      inducing bilirubin impregnation of basal ganglia with secondary neuronal damage
      and necrosis. The worst outcome, kernicterus, is characterized by mental
      retardation, central deafness, ophthalmoplegia, ataxia, athetosis, spasticity,
      seizures and death. First line therapy includes phototherapy, but definitive
      therapy is liver transplantation before the occurrence of neurological damage. 

PMID- 24861124
TI  - [Emphysematous cystitis: report of one case].
AB  - We report a 53 year-old woman with type 2 diabetes mellitus and hypertension,
      presenting with progressive abdominal pain lasting three weeks, associated with
      lower abdominal swelling and fever. Clinical examination showed a large increase
      in abdominal volume, contraction of extracellular compartment, and signs of
      severe sepsis. Computed tomography showed an over-distended bladder with severe
      wall and luminal pneumatosis and bilateral hydronephrosis. The diagnosis was of
      emphysematous cystitis associated to hydronephrosis. Urine and blood cultures
      were positive for multi-susceptible Escherichia coli. Clinical evolution was
      favorable after 6 weeks of ceftriaxone and urinary catheter use. Emphysematous
      cystitis is a rare clinical entity, with an associated mortality of 7%. Known
      predisposing factors are older age, female gender and presence of diabetes.
      Microbiological agents most frequently involved are Escherichia coli and
      Klebsiella pneumoniae (80% of cases). Medical treatment is preferred and is based
      on urinary tract decompression with a bladder catheter, and prolonged broad
      spectrum antimicrobial therapy. 

PMID- 24861126
TI  - [Atmosphere, The scream and Edvard Munch].

PMID- 24861125
TI  - [Skin necrosis: report of eleven cases].
AB  - Skin necrosis must be considered as a syndrome, because it is a clinical
      manifestation of different diseases. An early diagnosis is very important to
      choose the appropriate treatment. Therefore, its causes should be suspected and
      confirmed quickly. We report eleven patients with skin necrosis seen at our
      Department, caused by different etiologies: Warfarin-induced skin necrosis,
      loxoscelism, diabetic microangiopathy, ecthyma gangrenosum, disseminated
      intravascular coagulation, necrotizing vasculitis, paraneoplastic extensive
      necrotizing vasculitis, livedoid vasculopathy, necrotizing fasciitis, necrosis
      secondary to the use of vasoactive drugs and necrosis secondary to the use of
      cocaine. We also report the results of our literature review on the subject. 

PMID- 24861127
TI  - [Atmosphere, The scream and Edvard Munch: Reply].

PMID- 24861128
TI  - [Binge eating disorder: officially recognized as the new eating disorder].

PMID- 24861130
TI  - Comments on "Biofilms of Candida albicans serotypes A and B differ in their
      sensitivity to photodynamic therapy".

PMID- 24861129
TI  - Treating epilepsy in the setting of medical comorbidities.
AB  - OPINION STATEMENT: Treatment of epilepsy in patients with medical comorbidities
      can be challenging. Comorbidities can affect medical management and quality of
      life. In this review, we discuss treatment options in patients with epilepsy and
      medical comorbidities. In our opinion, the best way to manage patients with
      medical comorbidities and epilepsy is to accurately recognize and diagnose
      medical comorbidities, and to have adequate knowledge and familiarity with
      antiepileptic drug (AED) metabolism, dosing, side effects, and drug interactions.
      We believe the trend should move toward using the newer generation of AEDs given
      their generally reduced rate of adverse effects and interactions. The primary
      goal of therapy is seizure freedom without side effects.

PMID- 24861131
TI  - Serum prolactin and CA-125 levels as biomarkers of peritoneal endometriosis.
AB  - BACKGROUND/AIMS: To evaluate serum prolactin and CA-125 levels as biomarkers for
      the diagnosis of peritoneal endometriosis. METHODS: A prospective study was
      performed. Blood samples were drawn from a peripheral vein during the secretory
      phase of the menstrual cycle (day 19-21 prior to the surgery) to analyze through
      relative operating characteristic curve the serum prolactin and CA-125 levels for
      diagnosis of peritoneal endometriosis. The study was performed with 97
      participants, 63 women with peritoneal endometriosis and 34 healthy women.
      RESULTS: The sensitivity and specificity of peritoneal endometriosis diagnosis
      were equivalent for prolactin (21 and 99%) and for CA-125 (27 and 97%; p = 0.58).
      These two markers were used in a parallel test utilizing the usual cutoff
      (prolactin 20.0 ng/ml and CA-125 35 U/I). The sensitivity and specificity were 44
      and 99%. However, by utilizing the best cutoff (prolactin 14.8 ng/ml and for CA
      125 19.8 U/I), sensitivity, specificity and negative predictive value were 77, 88
      and 97%, respectively. CONCLUSION: Serum CA-125 and prolactin levels assessed
      together, and considering the cutoff for CA-125 (19.9 U/I) and prolactin (14.8
      ng/ml), allow the diagnosis of peritoneal endometriosis with acceptable
      sensitivity and specificity (77 and 88%) and a high negative predictive value
      (97%).

PMID- 24861132
TI  - Age-related changes in tissue macrophages precede cardiac functional impairment.
AB  - Cardiac tissue macrophages (cTMs) are abundant in the murine heart but the extent
      to which the cTM phenotype changes with age is unknown. This study characterizes
      aging-dependent phenotypic changes in cTM subsets. Using theCx3cr1(GFP/+) mouse
      reporter line where GFP marks cTMs, and the tissue macrophage marker Mrc1, we
      show that two major cardiac tissue macrophage subsets, Mrc1-GFP(hi) and
      Mrc1+GFP(hi) cTMs, are present in the young (<10 week old) mouse heart, and a
      third subset, Mrc1+GFP(lo), comprises ~50% of total Mrc1+ cTMs from 30 weeks of
      age. Immunostaining and functional assays show that Mrc1+ cTMs are the principal
      myeloid sentinels in the mouse heart and that they retain proliferative capacity
      throughout life. Gene expression profiles of the two Mrc1+ subsets also reveal
      that Mrc1+GFP(lo) cTMs have a decreased number of immune response genes (Cx3cr1,
      Lpar6, CD9, Cxcr4, Itga6 and Tgfbetar1), and an increased number of fibrogenic
      genes (Ltc4s, Retnla, Fgfr1, Mmp9 and Ccl24), consistent with a potential role
      for cTMs in cardiac fibrosis. These findings identify early age-dependent gene
      expression changes in cTMs, with significant implications for cardiac tissue
      injury responses and aging-associated cardiac fibrosis.

PMID- 24861133
TI  - Pharmacokinetic interaction study of ticagrelor and cyclosporine in healthy
      volunteers.
AB  - BACKGROUND AND OBJECTIVE: Patients with acute coronary syndrome and certain co
      morbidities may receive ticagrelor, a reversibly binding P2Y(12) receptor
      antagonist, and cyclosporine, a commonly used immunosuppressant drug. This study
      assessed the potential pharmacokinetic drug-drug interaction between ticagrelor
      and cyclosporine. METHODS: In this single-centre, open-label, three-treatment,
      three-period crossover study (NCT01504906), healthy volunteers (n = 26) randomly
      received each of three treatments: cyclosporine (600 mg single oral dose) plus
      ticagrelor (180 mg single oral dose); cyclosporine alone; ticagrelor alone.
      Treatments were separated by a washout period of >=14 days. Plasma concentrations
      of ticagrelor and its active metabolite (AR-C124910XX) and blood concentrations
      of cyclosporine were analyzed, and pharmacokinetic parameters were calculated.
      Safety and tolerability were assessed. RESULTS: Compared with ticagrelor alone,
      the geometric least squares mean (LSM) ratio (90 % confidence interval [CI]) for
      the ticagrelor area under the plasma concentration-time curve from time zero to
      infinity (AUC(infinity)) was 2.83 (2.63-3.06), and the maximum plasma
      concentration (C(max)) was 2.30 (2.06-2.58), in the presence of cyclosporine. Co
      administration of cyclosporine with ticagrelor significantly increased AR
      C124910XX AUC(infinity) (1.33 [1.23-1.42]) and decreased C(max) (0.85 [0.76
      0.94]). Ticagrelor had no effect on cyclosporine pharmacokinetic parameters, as
      the 90 % CIs of the LSM ratios were all within the 0.80-1.25 no-effect range. Co
      administration of ticagrelor and cyclosporine was generally well tolerated.
      CONCLUSION: Co-administration of cyclosporine with ticagrelor increased exposure
      to ticagrelor and its active metabolite and had no effect on cyclosporine
      pharmacokinetic parameters. The magnitude of cyclosporine's effect on ticagrelor
      pharmacokinetics does not warrant dose adjustment of ticagrelor.

PMID- 24861134
TI  - Investigation of the effect of macitentan on the pharmacokinetics and
      pharmacodynamics of warfarin in healthy male subjects.
AB  - BACKGROUND AND OBJECTIVES: Macitentan is a novel dual endothelin receptor
      antagonist recently approved for the treatment of pulmonary arterial hypertension
      (PAH). Warfarin, an anticoagulant often prescribed to patients with PAH, has a
      narrow therapeutic index and is prone to potential interactions with drugs. This
      study assessed the effects of macitentan on the pharmacokinetics and
      pharmacodynamics of single-dose warfarin in healthy subjects. METHODS: This was a
      randomised, open-label, single-centre, two-way crossover (treatment A followed by
      treatment B, or vice versa), phase I study in 14 healthy male subjects. Treatment
      A was a loading dose of macitentan 30 mg on Day 1 followed by 10 mg once daily
      for 8 days, with a single 25 mg dose of warfarin on Day 4. Treatment B was a
      single dose of warfarin on Day 1. Blood samples were assessed for warfarin
      pharmacokinetics (R- and S-warfarin) and pharmacodynamics [international
      normalised ratio (INR) and factor VII]. Plasma trough concentrations of
      macitentan and its active metabolite (ACT-132577) and the safety and tolerability
      of each treatment were also assessed. RESULTS: Plasma concentrations of R- and S
      warfarin were similar in both treatment periods. Warfarin did not affect the mean
      trough plasma concentrations of macitentan or ACT-132577. Macitentan did not
      affect the pharmacodynamics of warfarin; the mean INR and factor VII activity
      versus time profiles were similar with and without macitentan. CONCLUSIONS: The
      absence of effect of macitentan on the pharmacokinetics and pharmacodynamics of a
      single dose of warfarin suggests that both drugs can be concomitantly
      administered without need for dose adjustment.

PMID- 24861135
TI  - Non-radiation endoscopic retrograde cholangiopancreatography in the management of
      choledocholithiasis during pregnancy.
AB  - Gallstone diseases are common during pregnancy. In most cases, patients are
      asymptomatic and do not require any treatment. However, choledocholithiasis,
      cholangitis, and gallstone pancreatitis may potentially become life-threatening
      for both mother and fetus and often require urgent intervention. Although
      endoscopic retrograde cholangiopancreatography (ERCP) has become the standard
      technique for removing common bile duct stones, it is associated with ionizing
      radiation that could carry teratogenic risk. Non-radiation ERCP (NR-ERCP) is
      reported to be effective without incurring this risk. Two techniques have been
      described to confirm bile duct cannulation: bile aspiration and image guidance.
      With bile aspiration, biliary cannulation is confirmed by applying suction to the
      cannula to yield bile, thus confirming an intrabiliary position. Image guidance
      involves using ultrasound or direct visualization (choledochoscopy) to confirm
      selective biliary cannulation or duct clearance. Once cannulation is achieved,
      the stones are removed using standard ERCP techniques and tools. Case series and
      retrospective studies have reported success rates of up to 90% for NR-ERCP with
      complication rates similar to standard ERCP. Pregnancy outcomes are not adversely
      affected by NR-ERCP, but whether the avoidance of radiation carries benefit for
      the baby is unknown. Prospective comparative trials are lacking. NR-ERCP is
      technically demanding and should be attempted only by skilled biliary
      endoscopists in properly equipped and staffed health-care institutions, in a
      multidisciplinary setting. 

PMID- 24861136
TI  - The antennal sensilla of Melipona quadrifasciata (Hymenoptera: Apidae:
      Meliponini): a study of different sexes and castes.
AB  - The sensilla of insects are integumental units that play a role as sensory
      structures and are crucial for the perception of stimuli and for communication.
      In this study, we compared the antennal sensilla of females (workers and queens),
      males (haploid (n) and diploid (2n)), and queen-like males (QLMs, resulting from
      2n males after juvenile hormone (JH) treatment) in the stingless bee Melipona
      quadrifasciata. Images of the dorsal antenna surfaces were acquired using a
      scanning electron microscope. As reported for other hymenopterans, this species
      exhibits a heterogeneous sensillar distribution along the antennae. Thirteen
      different types of sensilla were found in the antennae of M. quadrifasciata:
      trichodea (subtypes I to VI), chaetica (subtypes I and II), placodea, basiconica,
      ampullacea, coeloconica, and coelocapitula. Sensilla trichodea I were the most
      abundant, followed by sensilla placodea, which might function in olfactory
      perception. Sensilla basiconica, sensilla chaetica I, sensilla coeloconica, and
      sensilla ampullacea were found exclusively in females. In terms of the
      composition and size of the sensilla, the antennae of QLMs most closely resemble
      those of the 2n male, although QLMs exhibit a queen phenotype. This study
      represents the first comparative analysis of the antennal sensilla of M.
      quadrifasciata. The differences found in the type and amount of sensilla between
      the castes and sexes are discussed based on the presumed sensillary functions. 

PMID- 24861137
TI  - Uptake and depuration of gold nanoparticles in Daphnia magna.
AB  - This study presents a series of short-term studies (total duration 48 h) of
      uptake and depuration of engineered nanoparticles (ENP) in neonate Daphnia magna.
      Gold nanoparticles (Au NP) were used to study the influence of size, stabilizing
      agent and feeding on uptake and depuration kinetics and animal body burdens. 10
      and 30 nm Au NP with different stabilizing agents [citrate (CIT) and
      mercaptoundecanoic acid (MUDA)] were tested in concentrations around 0.5 mg Au/L.
      Fast initial uptake was observed for all studied Au NP, with CIT stabilized Au NP
      showing similar rates independent of size and MUDA showing increased uptake for
      the smaller Au NP (MUDA 10 nm > CIT 10 nm, 30 nm > MUDA 30 nm). However, upon
      transfer to clean media no clear trend on depuration rates was found in terms of
      stabilizing agent or size. Independent of stabilizing agent, 10 nm Au NP resulted
      in higher residual whole-animal body burdens after 24 h depuration than 30 nm Au
      NP with residual body burdens about one order of magnitude higher of animals
      exposed to 10 nm Au NP. The presence of food (P. subcapitata) did not
      significantly affect the body burden after 24 h of exposure, but depuration was
      increased. While food addition is not necessary to ensure D. magna survival in
      the presented short-term test design, the influence of food on uptake and
      depuration kinetics is essential to consider in long term studies of ENP where
      food addition is necessary. This study demonstrates the feasibility of a short
      term test design to assess the uptake and depuration of ENP in D. magna. The
      findings underlines that the assumptions behind the traditional way of
      quantifying bioconcentration are not fulfilled when ENPs are studied.

PMID- 24861138
TI  - Modified endoscope-assisted partial-superficial parotidectomy through a
      retroauricular incision.
AB  - OBJECTIVES: The aim of this study was to evaluate the feasibility of an endoscope
      assisted partial parotidectomy through a modified retroauricular incision.
      PATIENTS AND METHODS: Thirty patients with benign parotid superficial lobe tumors
      with a diameter of 2.4 +/- 0.5 cm, located in the anterior portion of the
      inferior auricular lobule, underwent an endoscope-assisted partial-superficial
      parotidectomy. A retrograde approach through a small skin incision was used. An
      additional 30 patients who underwent conventional surgeries were used as
      controls. The operation time, operative bleeding volume and subjective
      satisfaction with the incision scar were compared between the groups. RESULTS:
      All operations were successfully performed. The endoscopic surgery duration (74.8
      +/- 15.7 min), bleeding volume (12.7 +/- 3.9 ml) and incision length (4.8 +/- 0.4
      cm) differed between the groups (p = 0.001). The mean patient satisfaction score
      was 8.6 +/- 1.2 in the endoscope-assisted surgery group and 5.4 +/- 1.3 in the
      control group (p = 0.001). There were no tumor recurrences during the 9-36 months
      of follow-up. CONCLUSION: Endoscope-assisted partial-superficial parotidectomy
      via a modified retroauricular incision is a feasible method for the treatment of
      benign parotid superficial lobe tumors located in the anterior portion of the
      inferior auricular lobule. The main advantage of this procedure was that the
      small operative scars improved the cosmetic results.

PMID- 24861142
TI  - Role of the transumbilical laparoscopic-assisted single-channel, single-port
      procedure in an interval appendectomy for pediatric mass-forming appendicitis: a
      preliminary retrospective analysis.
AB  - INTRODUCTION: A transumbilical laparoscopic-assisted single-channel, single-port
      procedure was introduced during laparoscopic interval appendectomy for mass
      forming appendicitis in children. The aim of this study was to evaluate the
      results of the original laparoscopic interval appendectomy. METHODS: This study
      analyzed 31 children who underwent laparoscopic interval appendectomy using a
      single-channel, single-port procedure. The appendectomy was usually planned 8-12
      weeks following initial conservative treatment. The procedure was a single
      channel surgery using a 12-mm single port. Both a 5-mm telescope and grasper were
      inserted simultaneously into the single channel. The grasper held the appendix,
      and an extracorporeal appendectomy was performed. RESULTS: Appendectomy was
      planned for 29 patients, as 2 patients deviated from the protocol. The procedure
      was successful in 21 patients (72.4%). An accessory port was necessary in eight
      patients, two of whom successfully underwent laparoscopic surgery; the remaining
      six were converted to open appendectomy. The average length of surgery was 43 min
      in the single-channel, single-port procedure. No postoperative complications
      occurred in any patient. CONCLUSION: The single-channel, single-port procedure
      was successfully performed in over 70% of the patients. This preliminary
      retrospective analysis indicates that the procedure is safe and potentially
      beneficial in children with mass-forming appendicitis who require laparoscopic
      interval appendectomy.

PMID- 24861139
TI  - ALS-FTD complex disorder due to C9ORF72 gene mutation: description of first
      Polish family.
AB  - BACKGROUND: Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD)
      are complex neurodegenerative disorders that can be either sporadic or familial
      and can overlap clinically and pathologically. We present the first Central
      Eastern European family with ALS-FTD syndrome due to a C9ORF72 repeat expansion.
      METHODS: We studied a family consisting of 37 family members, 6 of whom were
      genetically evaluated for C9ORF72 expansions. Family members were evaluated
      clinically, by history, and by chart review. RESULTS: Overall, 5 generations of
      the family were studied, and 6 affected family members were identified. All
      affected members were females and had a different clinical presentation, which
      was ALS, FTD or both. Among the genetically evaluated subjects, 5 carried a
      C9ORF72 expansion; 4 of these individuals remain clinically unaffected.
      CONCLUSION: Our report reveals that the hexanucleotide repeat expansion of
      C9ORF72, which is the most common genetic cause of ALS-FTD complex disorder, is
      also present in Central-Eastern Europe. Further studies are needed to assess the
      frequency of this expansion in the Polish population with familial as well as
      sporadic ALS, FTD and the ALS-FTD complex disorder.

PMID- 24861143
TI  - Achilles tendon ultrasonography may detect early features of psoriatic
      arthropathy in patients with cutaneous psoriasis.
AB  - BACKGROUND: Psoriatic arthropathy is a progressive and debilitating disease
      involving reduction of functional activity of the articulations with consequent
      deterioration of the patient's quality of life. The entheses represent the
      initial site of articular inflammation and the enthesis of the Achilles tendon is
      the first to be affected. In some patients with psoriasis, enthesitis may not be
      diagnosed because it is still asymptomatic. OBJECTIVES: To evaluate whether
      ultrasonography allows early diagnosis in a larger population and to identify
      significant alterations of enthesitis beyond increased thickness of the Achilles
      tendon. MATERIALS AND METHODS: The study was undertaken on 59 patients (16 women,
      43 men), with chronic plaque psoriasis and 59 patients with other dermopathies.
      The patients underwent echographic evaluation of the Achilles heel using a
      Voluson imaging system. The severity of the psoriasis was evaluated by the
      Psoriasis Area Severity Index and the enthesitis by the Glasgow Ultrasound
      Enthesitis Scoring System (GUESS). RESULTS: The GUESS score was higher in those
      patients with psoriasis compared with patients with other dermopathies. Among
      psoriatic patients, 22% (13 of 59) presented tendon thickness over 5.29 mm and
      irregular tendon structure. Other abnormalities affected the tendon in 12
      patients. In seven patients (12%) bursitis was also revealed. CONCLUSIONS: Our
      data confirm that ultrasonography is a sensitive technique which reveals
      enthesitis more frequently than clinical examination in patients affected by
      psoriasis. We suggest the use of ultrasonography of the Achilles tendon in early
      diagnosis of psoriatic arthropathy with the objective of preventing progression
      of the pathology.

PMID- 24861144
TI  - The effect of affect on memory of pain induced by tooth restoration.
AB  - OBJECTIVE: Memories of dental pain may influence both subsequent pain experiences
      during dental treatment and future decisions about whether to go to a dentist.
      The main aims of this study were to assess memory of pain and pain-related affect
      induced by tooth restoration. METHODS: A total of 39 women who underwent tooth
      restoration rated their state anxiety before dental treatment, and the intensity
      and unpleasantness of pain and the emotions they felt immediately after dental
      treatment. Either 3 months or 6 months later, the participants were asked to
      recall their state anxiety, the intensity and unpleasantness of pain and the
      emotions they had felt. RESULTS: Regardless of the length of recall delay,
      participants accurately remembered both pain intensity and unpleasantness.
      Although the state anxiety felt before the pain experience was found to be
      remembered accurately, the positive affect that accompanied pain was
      underestimated and the negative affect that accompanied pain was overestimated.
      Positive affect experienced, state anxiety experienced and recalled state anxiety
      accounted for 32% and 30%, respectively, of the total variance in recalled
      intensity and unpleasantness of pain. CONCLUSION: It is concluded that although
      dental pain is remembered accurately, affective variables, rather than
      experienced pain, have an effect on memory of pain.

PMID- 24861145
TI  - A case series of three US adults with Japanese encephalitis, 2010-2012.
AB  - BACKGROUND: Japanese encephalitis (JE) virus is the leading cause of vaccine
      preventable encephalitis in Asia. Although the risk for acquiring JE for most
      travelers to Asia is low, it varies based on the destination, season, trip
      duration, and activities. METHODS: We present case reports of three US adults who
      were infected with JE virus while traveling or residing in Asia. RESULTS: Among
      the three JE patients, the first made a 10-day trip to mainland China and
      participated in outdoor activities in a rural area, the second had been resident
      in Taiwan for 4 months, and the third, fatal case was an expatriate living in
      South Korea. CONCLUSIONS: JE should be considered in the differential diagnosis
      for any patient with an acute neurologic infection, who has recently been in a JE
      endemic country. Health-care providers should assess the itineraries of travelers
      to JE-endemic countries, provide guidance on personal protective measures to
      prevent vector-borne diseases, and consider recommending JE vaccine for travelers
      at increased risk for JE virus infection.

PMID- 24861146
TI  - Sleep-related eye symptoms and their potential for identifying driver sleepiness.
AB  - The majority of individuals appear to have insight into their own sleepiness, but
      there is some evidence that this does not hold true for all, for example treated
      patients with obstructive sleep apnoea. Identification of sleep-related symptoms
      may help drivers determine their sleepiness, eye symptoms in particular show
      promise. Sixteen participants completed four motorway drives on two separate
      occasions. Drives were completed during daytime and night-time in both a driving
      simulator and on the real road. Ten eye symptoms were rated at the end of each
      drive, and compared with driving performance and subjective and objective sleep
      metrics recorded during driving. 'Eye strain', 'difficulty focusing', 'heavy
      eyelids' and 'difficulty keeping the eyes open' were identified as the four key
      sleep-related eye symptoms. Drives resulting in these eye symptoms were more
      likely to have high subjective sleepiness and more line crossings than drives
      where similar eye discomfort was not reported. Furthermore, drivers having
      unintentional line crossings were likely to have 'heavy eyelids' and 'difficulty
      keeping the eyes open'. Results suggest that drivers struggling to identify
      sleepiness could be assisted with the advice 'stop driving if you feel sleepy
      and/or have heavy eyelids or difficulty keeping your eyes open'.

PMID- 24861148
TI  - Nestin and WT1 expression in atheromathous plaque neovessels: association with
      vulnerability.
AB  - INTRODUCTION: Neoangiogenesis is crucial for the progression and vulnerability of
      atheromasic lesions. Since adult vasa vasorum, which represent the
      neoangiogenetic burden of healthy arteries, constitutively express Nestin and
      Wilms Tumor (WT1), the aims of the present study are: i) to describe and quantify
      Nestin and WT1 in plaque neovessels; ii) to investigate the relationship between
      neovessel phenotype and plaque instability. METHODS: We prospectively evaluated
      49 consecutive carotid endarterectomy specimens. Histopathological
      characteristics were separately collected, particularly the intraplaque
      histological complications. Immunohistochemistry was carried out for CD34, Nestin
      and WT1; the density of positivity was evaluated for each marker. RT-PCR was
      performed to assess Nestin and WT1 mRNA levels on the first 10 plaques and on 10
      control arteries. RESULTS: Six (12.2%) plaques showed no neoangiogenesis. In the
      others, the mean immunohistochemical densities of CD34, Nestin, and WT1-positive
      structures were 41.88, 28.84 and 17.68/mm2. Among the CD34+ neovessels, 68% and
      42% expressed Nestin and WT1 respectively, i.e., nearly 36% of the neovessels
      resulted to be Nestin+/WT1-. Furthermore, complicated plaques (n=30) showed
      significantly more CD34 and Nestin-positive vessels than uncomplicated plaques
      (n=13; P=0.045 and P=0.009), while WT1 was not increased (P=0.139). RT-PCR
      confirmed that WT1 gene expression was 3-fold lower than Nestin gene in plaques
      (p=0.001). CONCLUSIONS: Plaque neoangiogenesis shows both a Nestin+/WT1- and a
      Nestin+/WT1+ phenotype. The Nestin+/WT1- neovessels are significantly more
      abundant in complicated (vulnerable) plaques. The identification of new
      transcription factors in plaque neoangiogenesis, and their possible regulation,
      can open new perspectives in the therapy of vulnerable plaques.

PMID- 24861147
TI  - Use of 'rainy day' autologous haemopoietic stem cells: a single-institution
      experience over 10 years.
AB  - BACKGROUND: High-dose chemotherapy and autologous haematopoietic stem cell
      transplantation is an important therapeutic modality in the treatment of many
      haematological malignancies. Generally, stem cells are collected close to the
      time of the transplant, but an alternative is to collect and cryopreserve cells
      at an early stage of the illness so they are available for later use ('rainy day
      harvesting'). Although this practice has been commonplace in Australia, there is
      little evidence to document eventual use of cells collected in this manner.
      METHODS: We conducted an audit of indications for and eventual transplantation of
      'rainy day' harvests performed at our institution over a 10-year period. RESULTS:
      Although there was some variation across different disease groups, we found that
      only 14% of cells were transplanted. The median delay to transplantation was 19
      months. CONCLUSION: Together with recent advances in stem cell mobilisation
      techniques, results from this audit suggest that the practice may not be an
      effective use of limited health resources.

PMID- 24861149
TI  - ArsH from Synechocystis sp. PCC 6803 reduces chromate and ferric iron.
AB  - ArsH is widely distributed in bacteria, and its function remains to be
      characterized. In this study, we investigated the function of ArsH from
      Synechocystis sp. PCC 6803. The inactivation of arsH by insertion of a kanamycin
      resistance gene in Synechocystis sp. PCC 6803 resulted in the decrease of arsenic
      and chromium accumulation compared with the wild type. ArsH expression in
      Escherichia coli strain Rosetta increased its resistance to chromate by reducing
      chromate in the medium and cells to chromium (III). In addition, ArsH in Rosetta
      conferred resistance to arsenic. The purified Synechocystis ArsH was able to
      reduce chromate and ferric iron at the expense of NADPH. Nonlinear regression
      values of K0.5 for chromate and ferric iron were 71.9 +/- 17.8 MUM and 59.3 +/-
      13.8 MUM, respectively. The expression level of arsH was induced by arsenite and
      arsenate, but not chromate or ferric iron. Our results suggest that Synechocystis
      ArsH had no substrate specificities and shared some biochemical properties that
      other enzymes possessed. ArsH may be involved in coordinating oxidative stress
      response generated by arsenic.

PMID- 24861150
TI  - Infestation of urban populations of the Northern white-breasted hedgehog,
      Erinaceus roumanicus, by Ixodes spp. ticks in Poland.
AB  - Infestation by the nest-dwelling Ixodes hexagonus Leach and the exophilic Ixodes
      ricinus (Linnaeus) (Ixodida: Ixodidae) on the Northern white-breasted hedgehog,
      Erinaceus roumanicus (Erinaceomorpha: Erinaceidae), was investigated during a 4
      year study in residential areas of the city of Poznan, west-central Poland. Of
      341 hedgehogs, 303 (88.9%) hosted 10 061 Ixodes spp. ticks encompassing all
      parasitic life stages (larvae, nymphs, females). Ixodes hexagonus accounted for
      73% and I. ricinus for 27% of the collected ticks. Male hedgehogs carried
      significantly higher tick burdens than females. Analyses of seasonal prevalence
      and abundance of I. hexagonus revealed relatively stable levels of infestation of
      all parasitic stages, with a modest summer peak in tick abundance noted only on
      male hosts. By contrast, I. ricinus females and nymphs peaked in spring and
      declined steadily thereafter in summer and autumn, whereas the less abundant
      larvae peaked in summer. This is the first longterm study to evaluate the
      seasonal dynamics of both tick species on populations of wild hedgehogs
      inhabiting urban residential areas. 

PMID- 24861151
TI  - A new pollinating seed-consuming mutualism between Rheum nobile and a fly fungus
      gnat, Bradysia sp., involving pollinator attraction by a specific floral
      compound.
AB  - Pollinating seed-consuming mutualisms are regarded as exemplary models for
      studying coevolution, but they are extremely rare. In these systems, olfactory
      cues have been thought to play an important role in facilitating encounters
      between partners. We present a new pollinating seed-consuming mutualism from the
      high Himalayas between the endemic herb, Rheum nobile, and a fly fungus gnat,
      Bradysia sp. Seed production resulting from pollination by Bradysia flies and
      seed consumption by their larvae were measured to determine the outcome of this
      interaction. Floral scent analyses and behavioural tests were conducted to
      investigate the role of olfactory cues in pollinator attraction. Rheum nobile is
      self-compatible, but it depends mainly on Bradysia sp. females for pollination.
      Seed production resulting from pollination by adult flies is substantially higher
      than subsequent seed consumption by their larvae. Behavioural tests showed that
      an unusual floral compound, 2-methyl butyric acid methyl ester, emitted by plants
      only during anthesis, was attractive to female flies. Our results indicate that
      the R. nobile-Bradysia sp. interaction represents a new pollinating seed
      consuming mutualism, and that a single unusual compound is the specific signal in
      the floral scent of R. nobile that plays a key role in attracting its pollinator.

PMID- 24861152
TI  - Comparison of the effect of nonactivated self-adjusting file system, Vibringe,
      EndoVac, ultrasonic and needle irrigation on apical extrusion of debris.
AB  - AIM: To compare the effects of Vibringe, EndoVac, nonactivated SAF and passive
      ultrasonic irrigation (PUI) with a conventional syringe on the amount of apically
      extruded debris. METHODOLOGY: Seventy-five extracted human maxillary incisors
      were selected and randomly assigned to 5 groups (n = 15). The root canals were
      irrigated with Vibringe (Vibringe B. V. Corp, Amsterdam, Netherlands), EndoVac
      (Discus Dental, Smart Endodontics, Culver City, CA, USA), nonactivated SAF
      (ReDent-Nova, Ra'anana, Israel), passive ultrasonic irrigation (PUI) and
      conventional syringe. Distilled water was used as an irrigant, and debris was
      collected in pre-weighed glass vials. The tubes were then stored in an incubator
      at 37  degrees C for 10 days to evaporate the irrigant before weighing the dry
      debris. The mean weight of debris was assessed, and one-way analysis of variance
      was used for comparison of values and post hoc Tukey's test was used between
      groups (P = 0.05). RESULTS: The SAF group extruded significantly less debris than
      PUI and Vibringe groups (P < 0.05). There were no significant difference between
      needle, Vibringe and EndoVac groups (P > 0.05). CONCLUSIONS: All irrigation
      systems were associated with apical extrusion of debris. Nonactivated SAF
      extruded significantly less than Vibringe, EndoVac, passive ultrasonic and
      syringe irrigation.

PMID- 24861153
TI  - Administration of recombinant human granulocyte-colony-stimulating factor does
      not induce long-lasting detectable epigenetic alterations in healthy donors.
AB  - BACKGROUND: The short-term safety profile of recombinant human granulocyte-colony
      stimulating factor (rHuG-CSF) in the allogeneic stem cell setting seems
      acceptable; only few data on long-term safety are available. To further study
      possible epigenetic alterations, we investigated prospectively the influence of
      rHuG-CSF on DNA methyltransferase (DNMT) activity and on changes in DNA
      methylation of candidate genes in peripheral blood cells of healthy unrelated
      stem cell donors within an observation period of 1 year. STUDY DESIGN AND
      METHODS: In this study, 20 stem cell donors (14 male/six female; median age, 40
      years; range, 22-54 years) and 20 sex- and age-matched blood component donors
      (controls) were included. Sampling was performed before rHuG-CSF administration;
      at the time of donation; and on Days (+1), 7, 30, 100, 180, and 360 in both
      groups. Analysis of DNMT activity in nuclear extracts was performed using a
      modified radionuclide assay. We performed methylation-specific polymerase chain
      reaction to detect the methylation status of promoter CpG islands of the genes of
      the retinoic acid receptor beta (RAR-B) and the Ras association domain family 1A
      (RASSF1A). RESULTS: DNMT activity increased significantly on the day of donation
      and 1 day after (p < 0.05). By Day +7 baseline values were reached. No further
      significant alterations of DNMT activity in the treated group compared to the
      controls were observed. We could not detect any differences in the gene
      methylation of RAR-B and RASSF1A between both groups. CONCLUSION: In our
      prospective study no evidence of long-lasting increased DNMT activity or enhanced
      DNA methylation in a limited panel of target genes after recombinant human G-CSF
      administration was observed in healthy stem cell donors.

PMID- 24861154
TI  - Maintenance therapy in patients following the surgical treatment of peri
      implantitis: a 5-year follow-up study.
AB  - AIM: To evaluate the outcomes of conventional periodontal maintenance therapy on
      patients surgically treated for peri-implantitis. MATERIAL AND METHODS: 27
      patients with 149 dental implants were monitored during 5 years every 6 months.
      At each recall visit, the prostheses were removed to have proper access for
      implant examination and supra- and sub-gingival instrumentation. Sub-gingival
      instrumentation was performed using an ultrasonic instrument with under 0.12%
      chlorhexidine irrigation. RESULTS: At baseline (6 months following peri-implant
      surgery), 149 implants (78 not treated and 71 treated) were available for
      analysis. Of the 71 treated implants, 43 presented healthy peri-implant
      condition, while 28 had residual peri-implant pockets either of 4-5 mm or >= 6 mm
      associated with bleeding on probing/suppuration. The longitudinal evaluation
      revealed that the plaque and the bleeding index scores were low during the entire
      follow-up period, and healthy peri-implant conditions were maintained for both
      the 78 non-treated and the 43 treated "healthy" implants. Of the 28 implants with
      residual pockets, nine showed clinical attachment loss during the 5-year follow
      up. Thus, of 71 treated implants, probing attachment loss occurred in only in 9
      (13%) of the implants in four patients during the 5-year period. The presence of
      residual pockets at three or four sites of the implants (circumferential type of
      pockets) was frequently associated with increased probing pocket depth (PPD) and
      attachment loss, while this was not the case for implants with the presence of
      pockets at one or two sites only (site specific). CONCLUSION: In patients with a
      high standard of oral hygiene and enrolled in a recall system every 6 months, the
      peri-implant conditions obtained following peri-implant surgery were maintained
      stable for the majority of subjects and implants during a 5-year period. Presence
      of residual pockets around the circumference of the implants seemed to be a high
      predictor for disease progression.

PMID- 24861155
TI  - The (dis)unity of nursing science.
AB  - This paper looks at the implications of contemporary work in philosophy of
      science for nursing science. Early work on the nature of theories in nursing was
      strongly influenced by logical empiricism, and this influence remains even long
      after nurse scholars have come to reject logical empiricism as an adequate
      philosophy of science. Combined with the need to establish nursing as an
      autonomous profession, nursing theory's use of logical empiricism has led to
      serious conceptual problems. Philosophers of science have also rejected many of
      the central tenets of logical empiricism, including its focus on the logical
      justification of theories and the idea that science is, or should be, unified.
      Instead, there has been an increasing focus on the practice of science, which in
      turn has led to a pluralist understanding of science that emphasizes the
      construction of scientific models that are appropriate for certain purposes or in
      certain contexts. I suggest that this approach to philosophy of science may
      provide better resources for nursing science. 

PMID- 24861156
TI  - Impaired metabolic control and socio-demographic status in immigrant children at
      onset of Type 1 diabetes.
AB  - AIM: The aim of the present study was to compare clinical and socio-demographic
      conditions at the onset of Type 1 diabetes in children born to immigrant families
      and children born to Swedish families, and to assess whether those conditions had
      an impact on metabolic status. METHODS AND DESIGN: This was an observational
      nationwide population-based matched cohort study on prospectively recorded
      registry data of all children with diabetes in Sweden and their families during
      2000-2010. Out of a total of 13 415 children from the Swedish Childhood Diabetes
      Registry (SWEDIABKIDS), 879 children born to immigrant parents were collected. To
      these we added 2627 children with Swedish-born parents, matched for gender, age
      and year of onset of Type 1 diabetes. RESULTS: The proportion of low capillary pH
      (< 7.30) at onset was higher in the immigrant cohort [25.8% vs. 16.4% in the
      Swedish cohort (P < 0.001)]. HbA1c was also higher [95 mmol/mol (10.8%) vs. 88
      mmol/mol (10.2%), respectively (P < 0.001)]. In a logistic regression model with
      low pH as the dependent variable, we were unable to reveal any significant
      association to socio-demographic factors, but the odds ratio for HbA1c was 0.983
      (95% CI 0.976-0.991) and for plasma glucose was 0.953 (95% CI 0.933-0.973).
      CONCLUSION: Children born to immigrant parents have lower capillary pH and higher
      HbA1c at diabetes onset. Immigrant families harbour lower socio-demographic
      living conditions, but this fact does not seem to influence the inferior
      metabolic condition at diabetes onset.

PMID- 24861157
TI  - Esophageal distension during bolus transport: can it be detected by intraluminal
      impedance recordings?
AB  - BACKGROUND: Esophageal multiple intraluminal impedance (MII) measurement has been
      used to detect gastro-esophageal reflux and bolus transport. It is not clear if
      MII can detect changes in luminal cross sectional area (CSA) during bolus
      transport. Intraluminal ultrasound (US) images, MII, and high resolution
      manometry (HRM) were recorded simultaneously to determine temporal relationship
      between CSA and impedance during esophageal bolus transport and to define the
      relationship between peak distension and nadir impedance. METHODS: Studies were
      conducted in five healthy subjects. MII, HRM, and US images were recorded 6 cm
      above LES. Esophageal distensions were studied during swallows and injections of
      0.5 N saline bolus into the esophagus. KEY RESULTS: Temporal change in esophageal
      CSA correlates with changes in impedance (r-value: mean +/- SD = -0.80 +/- 0.08,
      range: -0.94 to -0.66). Drop in impedance during distension occurs as a two-step
      process; initial large drop associated with onset of CSA increase, followed by a
      small drop during which majority of the CSA increase occurs. Peak CSA and nadir
      impedance occur within 1 s of each other. Increase in swallow and injection
      volumes increased the CSA, had no effect on large drop but increased the small
      drop amplitude. We observed a significant correlation between peak CSA and nadir
      impedance (r = -0.90, p < 0.001) and a better correlation between peak CSA and
      inverse impedance (r = 0.94, p < 0.001). CONCLUSIONS & INFERENCES: Further
      studies are needed to confirm that intraluminal impedance recordings may be used
      to measure luminal CSA during esophageal bolus transport.

PMID- 24861158
TI  - Hippocampus and cerebral cortex present a different autophagic response after
      oxygen and glucose deprivation in an ex vivo rat brain slice model.
AB  - AIMS: To evaluate the neuroprotective role of autophagy in the cerebral cortex
      and hippocampus using an ex vivo animal model of stroke in brain slices. METHODS:
      Brain slices were maintained for 30 min in oxygen and glucose deprivation (OGD)
      followed by 3 h in normoxic conditions to simulate the reperfusion that follows
      ischaemia in vivo (RL, reperfusion-like). Phagophore formation (Beclin 1 and
      LC3B) as well as autophagy flux (p62/SQSTM1, Atg5, Atg7 and polyubiquitin)
      markers were quantified by Western blot and/or qPCR. The release of lactate
      dehydrogenase (LDH) and glutamate in the medium was used as a measure of the
      mortality in the absence and in the presence of the autophagy inhibitor 3
      methyladenine. RESULTS: Striking differences in the autophagy markers were
      observed between the hippocampus and cerebral cortex in normoxic conditions.
      OGD/RL induced increases both in the phagophore formation and in the autophagy
      flux in the first three hours in the cerebral cortex that were not observed in
      the hippocampus. The blocking of autophagy increased the OGD/RL-induced
      mortality, increased the glutamate release in both the cerebral cortex and
      hippocampus and abolished the OGD-induced decrease in the polyubiquitinated
      proteins in the cerebral cortex. CONCLUSIONS: We conclude that OGD induces a
      rapid autophagic response in the cerebral cortex that plays a neuroprotective
      role. Polyubiquitination levels and control of the glutamate release appear to be
      involved in the neuroprotective role of autophagy.

PMID- 24861159
TI  - Intelligibility as a clinical outcome measure following intervention with
      children with phonologically based speech-sound disorders.
AB  - BACKGROUND: The effectiveness of two treatment approaches (phonological therapy
      and articulation therapy) for treatment of 14 children, aged 4;0-6;7 years, with
      phonologically based speech-sound disorder (SSD) has been previously analysed
      with severity outcome measures (percentage of consonants correct score,
      percentage occurrence of phonological processes and phonetic inventory).
      Considering that the ultimate goal of intervention for children with
      phonologically based SSD is to improve intelligibility, it is curious that
      intervention studies focusing on children's phonology do not routinely use
      intelligibility as an outcome measure. It is therefore important that the impact
      of interventions on speech intelligibility is explored. AIMS: This paper
      investigates the effectiveness of the two treatment approaches (phonological
      therapy and articulation therapy) using intelligibility measures, both in single
      words and in continuous speech, as the primary outcome. METHODS & PROCEDURES:
      Fourteen children with phonologically based SSD participated in the intervention.
      The children were randomly assigned to phonological therapy or articulation
      therapy (seven children in each group). Two assessment methods were used for
      measuring intelligibility: a word identification task (for single words) and a
      rating scale (for continuous speech). Twenty-one unfamiliar adults listened and
      judged the children's intelligibility. Reliability analyses showed overall high
      agreement between listeners across both methods. OUTCOMES & RESULTS: Significant
      improvements were noted in intelligibility in both single words (paired
      t(6)=4.409, p=0.005) and continuous speech (asymptotic Z=2.371, p=0.018) for the
      group receiving phonology therapy pre- to post-treatment, but no differences in
      intelligibility were found for those receiving the articulation therapy pre- to
      post-treatment, either for single words (paired t(6)=1.763, p=0.128) or
      continuous speech (asymptotic Z=1.442, p=0.149). CONCLUSIONS & IMPLICATIONS:
      Intelligibility measures were sensitive enough to show changes in the
      phonological therapy group but not in the articulation therapy group. These
      findings emphasize the importance of using intelligibility as an outcome measure
      to complement the results obtained with other severity measures when exploring
      the effectiveness of speech interventions. This study presents new evidence for
      the effectiveness of phonological therapy in improving intelligibility with
      children with SSD.

PMID- 24861160
TI  - Myocardial protection using del nido cardioplegia solution in adult reoperative
      aortic valve surgery.
AB  - BACKGROUND AND AIMS: The immediate postischemic period is marked by elevated
      intracellular calcium levels, which can lead to irreversible myocyte injury. Del
      Nido cardioplegia was developed for use in the pediatric population to address
      the inability of immature myocardium to tolerate high levels of intracellular
      calcium following cardiac surgery. Our aim in this study is to determine if this
      solution can be used safely and effectively in an adult, reoperative population.
      METHODS: All patients undergoing isolated reoperative aortic valve replacement at
      our institution from 2010 to 2012 were retrospectively reviewed. Demographics,
      comorbidities, operative variables, postoperative complications, and patient
      outcomes were collected. Patients were divided into two groups based on
      cardioplegia strategy used: whole blood cardioplegia (WB, n = 61) and del Nido
      cardioplegia (DN, n = 52). RESULTS: Mean age in the study was 73.4 +/- 14.3 years
      and 86 patients were male (76.1%). Eighty-four patients had undergone prior
      coronary artery bypass graft (CABG) (74.3%). Patients in the DN group required
      significantly lower total volume of cardioplegia (1147.6 +/- 447.2 mL DN vs.
      1985.4 +/- 691.1 mL WB, p < 0.001) and retrograde cardioplegia dose (279.3 +/-
      445.1 mL DN vs. 1341.2 +/- 690.8 mL WB, p < 0.001). There were no differences in
      cross-clamp time, bypass time, postoperative complication rate, or patient
      outcomes between groups. CONCLUSIONS: Del Nido cardioplegia use in an adult,
      reoperative aortic valve population offers equivalent postoperative outcomes when
      compared with whole blood cardioplegia. In addition, use of del Nido solution
      requires lower total and retrograde cardioplegia volumes in order to achieve
      adequate myocardial protection.

PMID- 24861161
TI  - Variable outcome for epilepsy after neonatal hypoglycaemia.
AB  - AIM: To evaluate the electroclinical features of epilepsy secondary to neonatal
      hypoglycaemia. METHOD: This was a retrospective study of children who had
      seizures beyond infancy after neonatal hypoglycaemia treated at The Royal
      Children's Hospital, Melbourne between 1996 and 2012. Patients with perinatal
      asphyxia were excluded. Clinical details were obtained from medical records.
      Digital electroencephalography (EEG) and brain magnetic resonance imaging (MRI)
      were reviewed. Eleven patients met the inclusion criteria (six males, five
      females; mean age 10y 5mo, range 4-18y at the time of review). RESULTS: Age at
      seizure onset ranged from 4 months to 5 years. Seizures were focal occipital in
      nine and generalized tonic in two patients. MRI showed gliosis with or without
      cortical atrophy in the occipital lobe with or without parietal lobe in all.
      Predominant EEG findings were stereotyped occipital sharp-slow discharges in
      five, polymorphic occipital spike-wave or paroxysmal fast activity in three, and
      generalized slow spike-wave and fast activity in two. Seizures were infrequent or
      remitted in six of the nine children with focal occipital seizures, and frequent
      and refractory in both children with generalized seizures. INTERPRETATION:
      Despite the common antecedent and bilateral occipital lobe injury, the seizure
      manifestations and course of epilepsy after neonatal hypoglycaemia were variable,
      with mild occipital, refractory occipital, and symptomatic generalized epilepsy
      recognized.

PMID- 24861162
TI  - Choosing to live in a nursing home: a culturally and linguistically diverse
      perspective.
AB  - As part of the findings of a study on culturally and linguistically diverse older
      people relocating to a nursing home, this paper contributes to our understanding
      of how older people draw on their cultural history to explain their decisions to
      relocate. Family reciprocity was identified by most participants as central to
      their decisions, regardless of their specific cultural origins. Using the
      grounded theory methodology, data were collected through progressive, semi
      structured, repeated, in-person, individual interviews with 20 residents of four
      nursing homes in the northern suburbs of Melbourne, Australia. Culturally and
      linguistically diverse (CALD) older people, regardless of specific cultural
      origin, make relocation decisions based on the importance and meaning of
      reciprocity within families. Understanding their decisions as reflecting a
      culturally valued reciprocity offered a sense of cultural continuity to the
      relocation and was comforting to the older adults involved in the study. This
      study also suggests that culturally and linguistically diverse older people are
      much more active participants in the decision to relocate to a nursing home than
      is commonly recognised. The four nursing homes in the northern suburbs of
      Melbourne and the 20 participants studied constitute only a small proportion of
      all culturally and linguistically diverse older nursing home residents in
      Australia. Therefore, the findings may not be pertinent to other culturally and
      linguistically diverse elderly. Nonetheless, this study makes an important
      contribution to future discussions regarding cultural diversity in the nursing
      home relocation of culturally and linguistically diverse older Australians. The
      study findings provide some insight into the conditions and contexts that impact
      nursing home relocation.

PMID- 24861164
TI  - The combined effect of side-coupled gain cavity and lossy cavity on the plasmonic
      response of metal-dielectric-metal surface plasmon polariton waveguide.
AB  - The combined effect of side-coupled gain cavity and lossy cavity on the plasmonic
      response of metal-dielectric-metal (MDM) surface plasmon polariton (SPP)
      waveguide is investigated theoretically using Green's function method. Our result
      suggests that the gain and loss parameters influence the amplitude and phase of
      the fields localized in the two cavities. For the case of balanced gain and loss,
      the fields of the two cavities are always of equi-amplitude but out of phase. A
      plasmon induced transparency (PIT)-like transmission peak can be achieved by the
      destructive interference of two fields with anti-phase. For the case of
      unbalanced gain and loss, some unexpected responses of structure are generated.
      When the gain is more than the loss, the system response is dissipative at around
      the resonant frequency of the two cavities, where the sum of reflectance and
      transmittance becomes less than one. This is because the lossy cavity, with a
      stronger localized field, makes the main contribution to the system response.
      When the gain is less than the loss, the reverse is true. It is found that the
      metal loss dissipates the system energy but facilitates the gain cavity to make a
      dominant effect on the system response. This mechanism may have a potential
      application for optical amplification and for a plasmonic waveguide switch. 

PMID- 24861165
TI  - Levels of pentraxin 3 and relationship with disease activity in patients with
      ankylosing spondylitis.
AB  - OBJECTIVE: Ankylosing spondylitis is a chronic inflammatory disease of the
      sacroiliac joint and vertebral column. Pentraxin (PTX) 3 is an acute phase
      protein known to be associated with chronic inflammation. This study was
      performed to test the hypothesis that serum PTX3 levels might be elevated as a
      marker of inflammation in patients with ankylosing spondylitis. MATERIAL AND
      METHODS: A total of 73 patients older than 20 years (48 males, 25 females, mean
      age 32.30 +/- 6.40 years) were included. The ankylosing spondilitis group
      consisted of 46 patients (18 females, 28 males, mean age 33.30 +/- 6.12 years)
      diagnosed with ankylosing spondilitis by the Modified New York Criteria, and the
      control group consisted of 27 healthy individuals (7 females, 20 males, mean age
      30.59 +/- 6.62 years). Groups were compared by demographic, anthropometric,
      biochemical data, and by serum PTX3 levels. The ankylosing spondilitis group was
      also divided into 2 subgroups (active or remission) by disease activity according
      to the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and compared
      by serum PTX3 levels. PTX3 was measured with the enzyme linked immunosorbent
      method. RESULTS: PTX3 levels were higher in the ankylosing spondylitis group
      compared to the control group (0.29 +/- 0.83 ng/mL vs. 0.09 +/- 0.06 ng/mL,
      p=0.009). Levels of serum PTX3 were similar in groups with active and remitted
      ankylosing spondilitis (0.34 +/- 0.99 ng/mL vs 0.37 +/- 1.15 ng/mL, p>0.05). No
      correlation was determined between PTX3 and disease activity (p>0.05).
      CONCLUSION: These results are supportive of the hypothesis that levels of serum
      PTX 3 might be elevated in association with inflammation in patients with
      ankylosing spondylitis; however, results also demonstrate that there is no
      significant correlation with disease activity.

PMID- 24861163
TI  - CpG methylation regulates allelic expression of GDF5 by modulating binding of SP1
      and SP3 repressor proteins to the osteoarthritis susceptibility SNP rs143383.
AB  - GDF5 encodes an extracellular signalling molecule that is essential for normal
      skeletal development. The rs144383 C to T SNP located in the 5'UTR of this gene
      is functional and has a pleiotropic effect on the musculoskeletal system, being a
      risk factor for knee-osteoarthritis (OA), congenital hip dysplasia, lumbar disc
      degeneration and Achilles tendon pathology. rs143383 exerts a joint-wide effect
      on GDF5 expression, with expression of the OA-associated T allele being
      significantly reduced relative to the C allele, termed allelic expression
      imbalance. We have previously reported that the GDF5 locus is subject to DNA
      methylation and that allelic imbalance of rs143383 is mediated by SP1, SP3 and
      DEAF1 transcriptional repressors. In this study, we have assayed GDF5 methylation
      in normal and osteoarthritic cartilage, and investigated the effect of
      methylation on the allelic imbalance of rs143383. We observed demethylation of
      the GDF5 5'UTR in OA knee cartilage relative to both OA (p = 0.009) and non-OA (p
      = 0.001) hip cartilage, with the most significant demethylation observed at the
      highly conserved +37 CpG site located 4 bp upstream of rs143383. Methylation
      modulates the level and direction of allelic imbalance of rs143383, with
      methylation of the +37 CpG dinucleotide within the SP1/SP3 binding site having an
      allele-specific effect on SP1 and SP3 binding. Furthermore, methylation
      attenuated the repressive effects of SP1, SP3 and DEAF1 on GDF5 promoter
      activity. This data suggest that the differential methylation of the +37 CpG site
      between osteoarthritic hip and knee cartilage may be responsible for the knee
      specific effect of rs143383 on OA susceptibility.

PMID- 24861168
TI  - Vertical phase separation in bulk heterojunction solar cells formed by in situ
      polymerization of fulleride.
AB  - Vertical phase separation of the donor and the acceptor in organic bulk
      heterojunction solar cells is crucial to improve the exciton dissociation and
      charge transport efficiencies. This is because whilst the exciton diffusion
      length is limited, the organic film must be thick enough to absorb sufficient
      light. However, it is still a challenge to control the phase separation of a
      binary blend in a bulk heterojunction device architecture. Here we report the
      realization of vertical phase separation induced by in situ photo-polymerization
      of the acrylate-based fulleride. The power conversion efficiency of the devices
      with vertical phase separation increased by 20%. By optimising the device
      architecture, the power conversion efficiency of the single junction device
      reached 8.47%. We believe that in situ photo-polymerization of acrylate-based
      fulleride is a universal and controllable way to realise vertical phase
      separation in organic blends. 

PMID- 24861167
TI  - Nanopore-based conformational analysis of a viral RNA drug target.
AB  - Nanopores are single-molecule sensors that show exceptional promise as a
      biomolecular analysis tool by enabling label-free detection of small amounts of
      sample. In this paper, we demonstrate that nanopores are capable of detecting the
      conformation of an antiviral RNA drug target. The hepatitis C virus uses an
      internal ribosome entry site (IRES) motif in order to initiate translation by
      docking to ribosomes in its host cell. The IRES is therefore a viable and
      important drug target. Drug-induced changes to the conformation of the HCV IRES
      motif, from a bent to a straight conformation, have been shown to inhibit HCV
      replication. However, there is presently no straightforward method to analyze the
      effect of candidate small-molecule drugs on the RNA conformation. In this paper,
      we show that RNA translocation dynamics through a 3 nm diameter nanopore is
      conformation-sensitive by demonstrating a difference in transport times between
      bent and straight conformations of a short viral RNA motif. Detection is possible
      because bent RNA is stalled in the 3 nm pore, resulting in longer molecular dwell
      times than straight RNA. Control experiments show that binding of a weaker drug
      does not produce a conformational change, as consistent with independent
      fluorescence measurements. Nanopore measurements of RNA conformation can thus be
      useful for probing the structure of various RNA motifs, as well as structural
      changes to the RNA upon small-molecule binding. 

PMID- 24861169
TI  - Obstacles to care in first-episode psychosis patients with a long duration of
      untreated psychosis.
AB  - AIM: This qualitative study is a sub-study of the early 'Treatment and
      Intervention in Psychosis Study' (TIPS-2), a program for early intervention
      strategies for people experiencing a first episode of psychosis. We aimed to
      improve knowledge about factors that prevent or delay patients with a long
      duration of psychosis from accessing psychiatric health-care services at an
      earlier illness stage and their personal views on the impact of ongoing
      informational campaigns (ICs) on help-seeking behaviour. METHOD: Following an
      interpretative-phenomenological approach, eight consecutive TIPS-2 patients with
      duration of untreated psychosis lasting for more than 6 months were interviewed.
      The interviews were analysed using a meaning condensation procedure. RESULTS:
      Five main themes were identified: (i) participants' failure to recognize symptoms
      of psychosis; (ii) difficulties expressing their experiences; (iii) concerns
      about stigma; (iv) poor psychosis detection skills among health-care
      professionals; and (v) participants' lack of awareness or understanding of ICs.
      CONCLUSIONS: The five themes identified may suggest that despite exposure to the
      targeted ICs, participants were unable to recognize or understand the severity of
      their symptoms. Further, although family members or others sometimes recognized
      the initial symptoms of psychosis development, these symptoms were attributed to
      reasons other than psychosis. Participants reported that health-care personnel
      also had trouble identifying emerging signs of psychosis. The ICs need to be
      carefully crafted to relay information to people who do not consider themselves
      as currently experiencing signs of psychosis.

PMID- 24861170
TI  - Natural infection with highly pathogenic avian influenza virus H5N1 in domestic
      pigeons (Columba livia) in Egypt.
AB  - The highly pathogenic avian influenza virus (HPAIV) subtype H5N1 threatens animal
      and human health worldwide. Susceptibility of pigeons to HPAIV (H5N1) and their
      role in avian influenza virus transmission to domestic birds and humans remain
      questionable. In this study, an outbreak in domestic pigeons (1 to 18 months old)
      with 50% mortality was investigated. Pigeons exhibited nervous manifestations and
      greenish diarrhoea. Necropsy of the naturally infected pigeons revealed
      congestion of the internal organs, particularly the lungs and brain. The HPAIV
      subtype H5N1 designated A/Pigeon/Egypt/SHAH-5803/2011 was isolated from a 40-day
      old pigeon. Sequencing of the haemagglutinin gene showed it to be closely related
      to viruses in group 2.2.1/C. Intravenous inoculation of the isolate in chickens
      induced 100% mortality within 2 days post inoculation and the intravenous
      pathogenicity index was 2.7. Virus pathogenicity and transmissibility was
      determined experimentally in 6-week-old domestic pigeons. Thirty per cent of
      pigeons inoculated oronasally with 10(6) median embryo infective dose showed
      congested beak, conjunctivitis, depression, and greenish diarrhoea. A mortality
      rate of 10% was recorded preceded by severe neurologic signs consisting of
      torticollis, incoordination, tremors, and wing paralysis. Pathological
      examination revealed a friable brain tissue and congested meningeal blood
      vessels. The lungs appeared oedematous and severely haemorrhagic. Subepicardial
      and petechial haemorrhages on the coronary fat were observed. Both infected and
      contact pigeons shed virus via the oropharynx and cloaca. To our knowledge, this
      is the first description and characterization of HPAIV in naturally infected
      pigeons in Egypt. Our findings reveal that pigeons can indeed be susceptible to
      H5N1 HPAIVs and could be a source of infection to other birds and humans. 

PMID- 24861166
TI  - Conformational targeting of intracellular Abeta oligomers demonstrates their
      pathological oligomerization inside the endoplasmic reticulum.
AB  - Abeta oligomers (AbetaOs) are crucially involved in Alzheimer's Disease (AD).
      However, the lack of selective approaches for targeting these polymorphic Abeta
      assemblies represents a major hurdle in understanding their biosynthesis, traffic
      and actions in living cells. Here, we established a subcellularly localized
      conformational-selective interference (CSI) approach, based on the expression of
      a recombinant antibody fragment against AbetaOs in the endoplasmic reticulum
      (ER). By CSI, we can control extra- and intracellular pools of AbetaOs produced
      in an AD-relevant cell model, without interfering with the maturation and
      processing of the Abeta precursor protein. The anti-AbetaOs intrabody selectively
      intercepts critical AbetaO conformers in the ER, modulating their assembly and
      controlling their actions in pathways of cellular homeostasis and synaptic
      signalling. Our results demonstrate that intracellular Abeta undergoes
      pathological oligomerization through critical conformations formed inside the ER.
      This establishes intracellular AbetaOs as key targets for AD treatment and
      presents CSI as a potential targeting strategy. 

PMID- 24861171
TI  - Comparative study of phytosterol derivatives in monovarietal olive oils.
AB  - Plant sterols and their derivatives are minor compounds that have been
      extensively studied in vegetable oils, mainly in olive oil, where they are
      closely related with its identity. The objective of this work is to determine the
      content of free and esterified steryl glucosides and their profiles in olive oil
      in relation to different geographical situation of olive orchards, cultivar,
      farming modality, and sampling time. The orchards under study were located in the
      outer ring of the submetropolitan area of Madrid (Spain), where olives from
      Cornicabra, Manzanilla Cacerena, Manzanilla Castellana, and Picual varieties were
      grown under traditional and organic modes, and harvested in four different
      samplings. Conclusions state that cultivar, farming mode, and light exposure do
      not have outstanding effects, whereas pedoclimate might affect the steryl
      glucoside presence in a substantial way. Further studies are being carried out
      presently in order to confirm such statement. Also glucoside derivative profiles
      are discussed, and reasons for differences with results in previous studies
      pointed out. 

PMID- 24861172
TI  - Live vs electronically delivered weight-loss interventions: paying for feasible
      interventions.

PMID- 24861173
TI  - [Health technology assessment].

PMID- 24861174
TI  - [Health Technology Assessment: conceptual framework and international
      perspective].
AB  - The increasing concerns of nations to improve efficiency, access and quality of
      health care, have encouraged a more appropriate use of health interventions.
      Thus, the interest of clinicians and decision-makers has shifted towards evidence
      based medicine, comparative effectiveness research and health technology
      assessment (HTA). Although these concepts should not be understood as synonyms,
      they converge on common characteristics: a systematic approach to evidence, the
      focus on relevant outcomes for the patient, and the notion that policy-making for
      a group of patients will affect others. As a consequence, concerns not only
      involve efficiency and effectiveness, but also transparency, clinical practice
      and opportunity costs. This paper introduces the concept and processes of HTA in
      the first and second sections. Section three reviews the evolution of HTA in
      developed and Latin-American countries, analyzing the aspects that influence the
      structure and scope of HTA. The last section concludes with reflections on the
      challenges to implement HTA in Chile. 

PMID- 24861175
TI  - [The main methodological aspects in Health Technology Assessment].
AB  - This article reviews the most relevant methodological aspects involved in Health
      Technology Assessment (HTA). Firstly, it addresses the process of defining the
      research problem (or scoping). Then it explains some specific aspects of
      systematic reviews of evidence, as well as indirect and mixed comparisons of the
      effectiveness of interventions. It covers also the methods for economic
      evaluation in healthcare and the budget impact analysis of interventions.
      Finally, the paper provides an empirical insight on the methodological emphasis
      used by HTA agencies around the world, and reflects on the available capacities
      in our country in the topics discussed. 

PMID- 24861176
TI  - [Priority setting for the health technology assessment].
AB  - The aim of this article is to analyze the different approaches of priority
      setting for health technology assessments (HTA). First, the paper identifies the
      reasons that make necessary to establish priorities and its importance for the
      success of the HTA models. Second, it studies the main stages that consider the
      determination of priorities based on the analysis of the models currently used by
      HTA agencies of developed countries. In the third place, the article describes
      the different criteria, methods of scoring and deliberation bodies included in
      the mechanism of priority setting of those agencies. Finally, the paper concludes
      mentioning lessons from the international experience that potentially can be an
      input for the design of a model of priority setting for HTA in our country. 

PMID- 24861177
TI  - [Citizen participation in the context of health technology assessment].
AB  - Citizen participation is important in all economic sectors of the democratic
      world, as it is also in the field of health. This is due to the significant value
      of life and therefore enjoying this in a healthy condition. This paper seeks to
      provide an overview of public participation in the context of Health Technology
      Assessments (HTA), covering from conceptualization to practical experiences.
      Within the existing literature, the definitions and methodological aspects of the
      topic discussed are reviewed, as well as how citizen participation in HTA
      agencies is manifested, presenting barriers as well as enablers for public
      involvement. In the Chilean case, where there are no public participation
      experiences in the context of HTA, a review of these initiatives in the health
      care sector is performed. In light with the studies examined, it is concluded
      that there is much to advance in the concreteness of citizen participation in
      HTA's agencies; efforts at institutional level as well as from community
      organizations are needed. This review can be useful as an antecedent for
      countries that are considering incorporating HTA in the future. 

PMID- 24861178
TI  - [Health technology assessment and its impact on pharmaceutical pricing and
      reimbursement policies].
AB  - The article conceptualizes the pharmaceutical pricing and reimbursement policies
      related to financial coverage in the context of health systems. It introduces the
      pharmaceutical market as an imperfect one, in which appropriate regulation is
      required. Moreover, the basis that guide the pricing and reimbursement processes
      are defined and described in order to generate a categorization based on whether
      they are intended to assess the 'added value' and if the evaluation is based on
      cost-effectiveness criteria. This framework is used to review different types of
      these policies applied in the international context, discussing the role of the
      Health Technology Assessment in these processes. Finally, it briefly discusses
      the potential role of these types of policies in the Chilean context. 

PMID- 24861179
TI  - [Health research and health technology assessment in Chile].
AB  - Health research is considered an essential element for the improvement of
      population health and it has been recommended that a share of the national health
      budget should be allocated to develop this field. Chile has undertaken efforts in
      the last decades in order to improve the governmental structure created to
      promote the development of health research, which has increased human resources
      and funding opportunities. On the other hand, the sustained economic growth of
      Chile in the last decades suggests that the health expenditure will maintain its
      increasing trend in the following years. This additional funding could be used to
      improve coverage of current activities performed in the health system, but also
      to address the incorporation of new strategies. More recently, health technology
      assessment (HTA) has been proposed as a process to support decisions about
      allocation of resources based on scientific evidence. This paper examines the
      relationship between the development of health research and the HTA process.
      First, it presents a brief diagnosis of the situation of health research in
      Chile. Second, it reviews the conceptual basis and the methods that account for
      the relationship between a HTA process and the development of health research. In
      particular, it emphasizes the relevance of identifying information gaps where
      funding additional research can be considered a good use of public resources.
      Finally, it discusses the challenges and possible courses of action that Chile
      could take in order to guarantee the continuous improvement of an articulated
      structure for health research and HTA. 

PMID- 24861180
TI  - [Equity in health and health technology assessment in Chile].
AB  - Equity has been recognized as one of the driving principles of many health
      systems in the world. In Latin America, Chile has led the explicit inclusion of
      equity in their health policies, which is reflected in its recent health reform.
      On the other hand, Chile faces the challenge of defining and implementing a
      policy for health technology assessment (HTA), which should be consistent with
      the equity principles that underlie the Chilean national health system. This
      paper reviews the equity concept emphasizing the relevance of socioeconomic
      inequalities. Furthermore, it examines how international HTA agencies have
      explicitly included this element in the evaluation and decision processes. It
      presents the English case, which highlights the elements of procedural justice
      rather than adopting a normative position regarding equity. Finally, it examines
      the methods that have been developed aiming to make explicit consideration of
      equity in HTA. It concludes that the methodological development to incorporate
      equity elements with empirical basis is recent and limited. The consideration of
      equity is, in most of the cases, left to the instances of deliberative
      participation. 

PMID- 24861181
TI  - [Foundations for the institutionalization of health technology assessment in
      Chile].
AB  - The Chilean health system has not been completely oblivious to health technology
      assessment (HTA). In fact, significant advances in the areas of health
      prioritization using criteria of disease burden, effectiveness and cost
      effectiveness among others, can be acknowledged. The introduction of the reform
      of Explicit Health Guarantees (GES) has been an important milestone in this
      arena, allowing the consideration of other dimensions such as social preferences
      in health. However, the application of HTA encompasses the entire health system
      and in that sense the institutionalization of a process properly defined and
      extensively validated in our country, is imminent. This paper discusses the
      foundations on which progress must be made in institutionalizing HTA, starting
      from the architecture of our health care system and in light of the economic and
      social reality. We review some background information first, and then discuss
      some important considerations in our context, including information on the
      institutional and legal framework. It concludes with the authors' view on some
      key elements to consider in HTA in Chile, which does not necessarily represent
      the vision of the Ministry of Health. 

PMID- 24861182
TI  - Acute liver failure-induced hepatic encephalopathy s associated with changes in
      microRNA expression rofiles in cerebral cortex of the mouse [corrected].
AB  - The mechanisms that promote brain dysfunction after acute liver failure (ALF) are
      not clearly understood. The small noncoding RNAs known as microRNAs (miRNAs)
      significantly control mRNA translation and thus normal and pathological functions
      in the mammalian body. To understand their significance in ALF, we currently
      profiled the expression of miRNAs in the cerebral cortex of mice sacrificed at
      coma stage following treatment with azoxymethane. Of the 470 miRNAs profiled
      using microarrays, 37 were significantly altered (20 up-and 17 down-regulated) in
      their expression in the ALF group compared to sham group. In silico analysis
      showed that the ALF-responsive miRNAs target on average 231 mRNAs/miRNA (range: 3
      to 840 targets). Pathways analysis showed that many miRNAs altered after ALF
      target multiple mRNAs that are part of various biological and molecular pathways.
      Glutamatergic synapse, Wnt signaling, MAP-kinase signaling, axon guidance, PI3
      kinase-AKT signaling, T-cell receptor signaling and ubiquitin-mediated
      proteolysis are the top pathways targeted by the ALF-sensitive miRNAs. At least
      28 ALF-responsive miRNAs target each of the above pathways. We hypothesize that
      alterations in miRNAs and their down-stream mRNAs of signaling pathways might
      play a role in the induction and progression of neurological dysfunction observed
      during ALF. 

PMID- 24861183
TI  - Desmosterol in brain is elevated because DHCR24 needs REST for Robust Expression
      but REST is poorly expressed.
AB  - Cholesterol synthesis in the fetal brain is inhibited because activity of DHCR24
      (24-dehydrocholesterol reductase) is insufficient, causing concentrations of the
      precursor desmosterol to increase temporarily to 15-25% of total sterols at
      birth. We demonstrate that failure of DHCR24 to be adequately upregulated during
      periods of elevated cholesterol synthesis in the brain results from the presence
      in its promoter of the repressor element 1 (RE1) nucleotide sequence that binds
      the RE1-silencing transcription factor (REST) and that REST, generally reduced in
      neural tissues, uncharacteristically but not without precedent, enhances DHCR24
      transcription. DHCR24 and REST mRNA levels are reduced 3- to 4-fold in fetal
      mouse brain compared to liver (p < 0.001). Chromatin immunoprecipitation assays
      suggested that REST binds to the human DHCR24 promoter in the vicinity of the
      predicted human RE1 sequence. Luminescent emission from a human DHCR24 promoter
      construct with a mutated RE1 sequence was reduced 2-fold compared to output from
      a reporter with wild-type RE1 (p < 0.005). Silencing REST in HeLa cells resulted
      in significant reductions of DHCR24 mRNA (2-fold) and DHCR24 protein (4-fold). As
      expected, relative concentrations of Delta(24)-cholesterol precursor sterols
      increased 3- to 4-fold, reflecting the inhibition of DHCR24 enzyme activity. In
      contrast, mRNA levels of DHCR7 (sterol 7-dehydrocholesterol reductase), a gene
      essential for cholesterol synthesis lacking an RE1 sequence, and concentrations
      of HMGR (3-hydroxy-3-methyl-glutaryl-CoA reductase) enzyme protein were both
      unaffected. Surprisingly, a dominant negative fragment of REST consisting of just
      the DNA binding domain (about 20% of the protein) and full-length REST enhanced
      DHCR24 expression equally well. Furthermore, RE1 and the sterol response element
      (SRE), the respective binding sites for REST and the SRE binding protein (SREBP),
      are contiguous. These observations led us to hypothesize that REST acts because
      it is bound in close proximity to SREBP, thus amplifying its ability to
      upregulate DHCR24. It is likely that modulation of DHCR24 expression by REST
      persisted in the mammalian genome either because it does no harm or because
      suppressing metabolically active DHCR24 while providing abundant quantities of
      the multifunctional sterol desmosterol during neural development proved useful.

PMID- 24861184
TI  - Coronary anomalies encountered in the acute setting: an imaging review.
AB  - A broad spectrum of congenital coronary anomalies may be discovered on imaging
      and sometimes in the emergency setting on computed tomography (CT). Most coronary
      artery anomalies are of academic interest; however, a minority can cause
      morbidity and mortality and symptoms such as angina, myocardial infarction, or
      arrhythmias. These anomalies are usually discovered as an incidental finding on
      CT examinations as part of the diagnostic workup for other pathology or on
      dedicated coronary computed tomography angiography (CCTA) as part of the
      evaluation for a coronary cause of chest pain. The purpose of this pictorial
      review is to demonstrate the types of coronary anomalies and to enhance the
      clinicians' understanding of the imaging classifications and clinical
      implications. 

PMID- 24861186
TI  - Stem cells: Does norepinephrine influence cartilage repair?

PMID- 24861187
TI  - Bone: The immune system takes control of bone homeostasis.

PMID- 24861188
TI  - Regenerative medicine: Selecting the right biological scaffold for tissue
      engineering.

PMID- 24861185
TI  - Mechanisms, impact and management of pain in rheumatoid arthritis.
AB  - People with rheumatoid arthritis (RA) identify pain as their most important
      symptom, one that often persists despite optimal control of inflammatory disease.
      RA pain arises from multiple mechanisms, involving inflammation, peripheral and
      central pain processing and, with disease progression, structural change within
      the joint. Consequently, RA pain has a wide range of characteristics-constant or
      intermittent, localized or widespread-and is often associated with psychological
      distress and fatigue. Dominant pain mechanisms in an individual are identified by
      critical evaluation of clinical symptoms and signs, and by laboratory and imaging
      tests. Understanding these mechanisms is essential for effective management,
      although evidence from preclinical models should be interpreted with caution. A
      range of pharmacological analgesic and immunomodulatory agents, psychological
      interventions and surgery may help manage RA pain. Pain contributes importantly
      to the clinical assessment of inflammatory disease activity, and noninflammatory
      components of RA pain should be considered when gauging eligibility for or
      response to biologic agents. Further randomized controlled trials are required to
      determine the optimal usage of analgesics in RA, and novel agents with greater
      efficacy and lower propensity for adverse events are urgently needed. Meanwhile,
      targeted use of existing treatments could reduce pain in people with RA. 

PMID- 24861190
TI  - Variation in small bowel length: factor in achieving total enteroscopy?
AB  - BACKGROUND AND AIM: Estimation of small bowel length is of interest following the
      recent development of device-assisted enteroscopy. This new technology allows
      access to the deep small bowel, but rates of examination of the entire small
      bowel (total enteroscopy) differ between study populations. Variation in small
      bowel length could factor into this observed irregularity in total enteroscopy
      rates. Medical literature contains limited information regarding small bowel
      length in living patients and conflicting data regarding small bowel length and
      its relationship to height and weight. We carried out small bowel measurements on
      surgical patients to further define the total length of the small bowel and its
      relationship to height, weight and body mass index (BMI). METHODS: Measurement of
      ileojejunal length on 91 surgical patients undergoing laparotomy for routine
      indications. Demographic data were collected for each subject, including height,
      weight and BMI. RESULTS: Small bowel length was found to vary widely between
      individuals (average 998.52 cm, range 630-1510 cm). Linear regression analysis
      demonstrated a statistically significant relationship between small bowel length
      and height (regression coefficient = 0.0561, P-value = 0.0238). A linear
      relationship between small bowel length and weight or BMI was not observed.
      CONCLUSIONS: Length of the small bowel in humans is pertinent to advances in deep
      enteroscopy and existing surgical applications such as intestinal bypass and
      prevention of short gut syndrome. If average small bowel length varies with
      height, total enteroscopy may be easier to achieve in patients who are short in
      stature.

PMID- 24861191
TI  - Iodine concentrations in Danish groundwater: historical data assessment 1933
      2011.
AB  - In areas where water is a major source of dietary iodine (I), the I concentration
      in drinking water is an important factor for public health and epidemiological
      understandings. In Denmark, almost all of the drinking water is originating from
      groundwater. Therefore, understanding the I variation in groundwater and
      governing factors and processes are crucial. In this study, we perform uni- and
      multivariate analyses of all available historical Danish I groundwater data from
      1933 to 2011 (n = 2,562) to give an overview on the I variability for first time
      and to discover possible geochemical associations between I and twenty other
      elements and parameters. Special attention is paid on the description and the
      quality assurance of this complex compilation of historical data. The high
      variability of I in Danish groundwater (<d.l. to 1,220 ug/l) is characterised by
      both small-scale heterogeneity and large-scale spatial trends, e.g. higher
      concentrations observed in the eastern part of Denmark. Significant trends are
      observed also with respect to the depth of extraction and geology, indicating the
      importance of older marine limestone and chalk deposits. A principal component
      analysis on centred log-ratio-transformed data (clr) revealed associations
      between I, Li, B, Ba, Br implying saline water influence. High I is also
      associated with reduced and alkaline groundwaters for this data set, dominated by
      Ca-HCO3 water type. 

PMID- 24861189
TI  - Consequences of renal failure on non-renal clearance of drugs.
AB  - Kidney disease not only alters the renal elimination but also the non-renal
      disposition of drugs that are metabolized by the liver. Indeed, modifications in
      the expression and activity of intestinal and hepatic drug metabolism enzymes and
      uptake and efflux transporters have been reported. Accumulated uremic toxins,
      inflammatory cytokines, and parathyroid hormones may modulate these proteins
      either directly or by inhibiting gene expression. This can lead to important
      unintended variations in exposure and response when drugs are administered
      without dose adjustment for reduced renal function. This review summarizes our
      current understanding of non-renal clearance in circumstances of chronic and
      acute renal failure with experimental but also clinical studies. It also
      evaluates the clinical impact on drug disposition. Predicting the extent of the
      drug disposition modification is difficult first because of the complex interplay
      between metabolic enzymes and transport proteins but also because of the
      differential effects in the different organs (liver, intestines). Recommendations
      of the US FDA are presented as they may be potentially helpful tools to predict
      these modifications when no specific pharmacokinetic studies are available.

PMID- 24861192
TI  - Comparison of hemodynamics after combined spinal-epidural anesthesia between
      decubitus and sitting positions in aged patients undergoing total hip
      replacement.
AB  - OBJECTIVE: To compare the hemodynamics after combined spinal-epidural anesthesia
      (CSEA) between decubitus and sitting positions in aged patients undergoing total
      hip replacement. METHODS: A total of 80 aged patients who underwent CSEA for
      elective total hip replacement were randomly divided into a decubitus position
      group (group D) and a sitting position group (group S; each group with 40
      patients). In group D, 10 mg of 0.5% bupivacaine were given into the subarachnoid
      space in decubitus position. In group S, 10 mg of 0.5% bupivacaine were given
      into the subarachnoid space in the sitting position, which was maintained for 1
      min, after which the patients were in decubitus position. In both groups, the
      sensory block levels and changes in hemodynamics were assessed. RESULTS: The mean
      arterial blood pressure was significantly higher in group S than in group D at
      each time point within 30 min after anesthesia. There were no significant
      differences in heart rate between the two groups at each time point. There was
      also no significant difference in the level of sensory block between the two
      groups 20 min after the administration of CSEA. CONCLUSION: For aged patients
      undergoing total hip replacement, CSEA is safer and more effective in the sitting
      position than in decubitus position.

PMID- 24861193
TI  - [Quality guidelines for presurgical epilepsy diagnosis and operative epilepsy
      therapy: 1st revised version].
AB  - In patients with pharmacorefractory epilepsy, preoperative epilepsy evaluation
      and subsequent epilepsy surgery lead to a significant improvement of seizure
      control, proportion of seizure-free patients, quality of life and social
      participation. The aims of preoperative epilepsy evaluation are to define the
      chance of complete seizure freedom and the likelihood of inducing new
      neurological deficits in a given patient. As epilepsy surgery is an elective
      procedure quality standards are particularly high. As detailed in the first
      edition of these practice guidelines, quality control relates to seven different
      domains: (1) establishing centres with a sufficient number of sufficiently and
      specifically trained personnel, (2) minimum technical standards and equipment,
      (3) continuing medical education of employees, (4) surveillance by trained
      personnel during the video electroencephalography (EEG) monitoring (VEM), (5)
      systematic acquisition of clinical and outcome data, (6) the minimum number of
      preoperative evaluations and epilepsy surgery procedures and (7) cooperation of
      epilepsy centres. In the first edition of these practice guidelines published in
      2000 it was defined which standards were desirable and that their implementation
      should be aimed for. These standards related especially to the certification
      required for different groups of medical doctors involved and to the minimum
      numbers of procedures required. In the subsequent decade quite a number of
      colleagues have been certified by the trinational Working Group
      (Arbeitsgemeinschaft, AG) for Presurgical Epilepsy Diagnosis and Operative
      Epilepsy Treatment (http://www.ag-epilepsiechirurgie.de) and therefore, on 8 May
      2013 the executive board of the AG decided to now make these standards
      obligatory.

PMID- 24861195
TI  - Significance of lupus erythematosus (LE) cell detection in pericardial fluid in
      an era of sophisticated techniques.

PMID- 24861194
TI  - [Antiepileptics in women of childbearing age and during pregnancy: comparison of
      specialized information with the current state of knowledge in Germany and
      Switzerland].
AB  - BACKGROUND: Healthcare professionals regularly read the summary of product
      characteristics (SmPC) as one of the various sources of information on the risks
      of drug use in women of childbearing age and during pregnancy. The aim of this
      article is to present an overview of the teratogenic potential of various
      antiepileptic drugs and to compare these data with the information provided by
      the SmPCs. METHODS: A literature search on the teratogenic risks of 19
      antiepileptic agents was conducted and the results were compared with the
      information on the use in women of childbearing age and during pregnancy provided
      by the SmPCs of 38 commercial products available in Switzerland and Germany.
      RESULTS: The teratogenic risk is discussed in all available SmPCs. Quantification
      of the risk for birth defects and the numbers of documented pregnancies are
      mostly missing. Reproductive safety information in SmPCs showed poor concordance
      with risk levels reported in the literature. Recommendations concerning the need
      to monitor plasma levels and possibly perform dose adjustments during pregnancy
      to prevent treatment failure were missing in five Swiss and two German SmPCs.
      DISCUSSION: The information regarding use in women of childbearing age and during
      pregnancy provided by the SmPCs is heterogeneous and poorly reflects the current
      state of knowledge. Regular updates of SmPCs are warranted in order for these
      documents to be of reliable use for health care professionals.

PMID- 24861197
TI  - Screening for Down syndrome--incidental diagnosis of other aneuploidies.
AB  - OBJECTIVE: Down syndrome screening programmes lead to the prenatal diagnosis of
      other chromosomal abnormalities, some of which would not be detected by the
      secondary use of cell-free (cf)DNA testing in screen positives. This study aims
      to assess the number of these incidental diagnoses. METHOD: This study is a
      systematic review of the literature to identify large prospective screening
      studies that reported diagnoses other than trisomies 21 and 18. RESULTS: There
      were ten informative prospective studies in which a total of 1,500,999 women were
      screened, and there were 3689 aneuploidy cases detected in the screen positives.
      Trisomy 21 was estimated to comprise only 58% of detected aneuploidies, trisomies
      21 and 18 comprised 72%, and the common trisomies - 21, 18 and 13 - comprised
      76%. Common trisomies and sex chromosome abnormalities, now included in all
      commercial cfDNA tests, were estimated to comprise 87% of aneuploidies in the
      Down syndrome screen positives. All these proportions were higher for second
      trimester protocols compared with those carried out wholly or partly in the first
      trimester. CONCLUSION: Secondary use of cfDNA testing will lead to about one
      fifth reduction in diagnoses, taking account of both undetectable aneuploidies
      and false-negatives. This loss might be overcome by contingent cfDNA testing.

PMID- 24861198
TI  - Fertility preservation in a patient with benign multicystic peritoneal
      mesothelioma.
AB  - Benign multicystic peritoneal mesothelioma (BMPM) is a rare peritoneal tumor.
      Surgery is the only effective treatment for BMPM, and affected tissues
      occasionally must be sacrificed to achieve adequate debulking. A 25-year-old
      female was diagnosed with BMPM. She was counseled on fertility preservation and
      had oocyte cryopreservation prior to her debulking. Fertility preservation
      through embryo or oocyte cryopreservation is a valuable option for patients at
      risk of losing reproductive tissues during extensive surgery and chemotherapy.

PMID- 24861196
TI  - A possible antineoplastic potential of selective, irreversible proteasome
      inhibitor, carfilzomib on chemically induced hepatocarcinogenesis in rats.
AB  - The antineoplastic effect of carfilzomib (CFZ) against chemically induced
      hepatocarcinogenesis was studied. A total of 60 male Wistar albino rats were
      divided into six groups with 10 animals in each group. Rats in group 1 (control
      group) were given dimethylsulphoxide (DMSO) (0.4 mL/kg i.p) twice a week for 3
      weeks from week 8 to week 10. Animals in groups 2 and 3 were given CFZ (2 and 4
      mg/kg i.p) twice a week from week 8 to week 10, respectively. Rats in group 4
      were given diethylnitrosamine (DENA) at a dose of 0.01% in drinking water for 10
      weeks and received a DMSO (0.4 mL/kg i.p) twice a week from week 8 to week 10.
      Animals in groups 5 and 6 were given DENA at a dose of 0.01% in drinking water
      for 10 weeks and treated with CFZ (2 and 4 mg/kg i.p) twice a week from week 8 to
      week 10, respectively. CFZ succeeded in suppressing the elevated serum tumor
      marker alpha-fetoprotein and carcinoembryonic antigen. The antineoplastic effect
      of CFZ was also accompanied by normalization of elevated hepatic tissue growth
      factors, matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-1,
      and augmentation of hepatic endostatin and metallothionein. A histopathological
      examination of liver samples treated with CFZ after DENA intoxication correlated
      with the biochemical observation. Treatment with CFZ confers an antineoplastic
      activity against chemically induced hepatocarcinogenesis. These findings suggest
      that CFZ plays a pivotal role in the treatment of hepatocarcinogenesis. 

PMID- 24861199
TI  - Synthesis of imidazole derivatives and study of the ON-based different memory
      performances.
AB  - We report the synthesis of two imidazole-based small molecules with different
      planarity of terminal aromatic rings and their application in memory devices with
      a sandwich configuration. The optical, electric, and the on-based device
      performances were systematically investigated. Surprisingly, the device based on
      BT-PMZ exhibited volatile static random access memory (SRAM) behavior, whereas
      that based on BT-BMZ showed nonvolatile write-once-read-many-times (WORM)
      behavior. Further studies on the film morphology and the molecular electronic
      structure were carried out to investigate the underlying mechanism for the large
      difference in their performance. Moreover, the performance of the device that
      incorporates a LiF buffer layer (5 nm) embedded at the interface between the BT
      BMZ active layer and the Al top electrode as well as that of the device with a
      cold-deposited top electrode of mercury droplet was further investigated. At that
      point a dramatic change in memory performance of the devices from the WORM to
      SRAM type was observed. The intrinsic volatile SRAM performance for the two
      molecules results from the moderate electron-withdrawing strength of the acceptor
      moieties and thus weak trapping of the charge carriers. 

PMID- 24861200
TI  - Zincocene and dizincocene N-heterocyclic carbene complexes and catalytic
      hydrogenation of imines and ketones.
AB  - The N-heterocyclic carbene (NHC) adducts Zn(Cp(R))(2) (NHC)] (Cp(R) =C(5)HMe(4),
      C(5)H(4) SiMe(3); NHC=ItBu, IDipp (Dipp=2,6-diisopropylphenyl), IMes
      (Mes=mesityl), SIMes) were prepared and shown to be active catalysts for the
      hydrogenation of imines, whereas decamethylzincocene [ZnCp*(2)] is highly active
      for the hydrogenation of ketones in the presence of noncoordinating NHCs. The
      abnormal carbene complex [Zn(OCHPh(2))(2) (aItBu)](2) was formed from spontaneous
      rearrangement of the ItBu ligand during incomplete hydrogenation of benzophenone.
      Two isolated Zn(I) adducts [Zn(2)Cp*(2) (NHC)] (NHC=ItBu, SIMes) are presented
      and characterized as weak adducts on the basis of (13)C NMR spectroscopic and X
      ray diffraction experiments. A mechanistic proposal for the reduction of
      [ZnCp*(2)] with H(2) to give [Zn(2)Cp*(2)] is discussed.

PMID- 24861201
TI  - Germ-cell culture conditions facilitate the production of mouse embryonic stem
      cells.
AB  - The derivation of embryonic stem-cell (ESC) lines from blastocysts is a very
      inefficient process. Murine ESCs are thought to arise from epiblast cells that
      are already predisposed to a primordial-germ-cell fate. During the process of ESC
      derivation from B6D2 F1 hybrid mice, if we first culture the embryo from the two
      cell stage in medium supplemented with LIF, we improve the quality of the
      blastocyst. When the blastocyst is then cultured in a germ-line stem-cell culture
      medium (GSCm), we are able to more efficiently (28.3%) obtain quality ESC lines
      that have a normal karyotype, proper degree of chimerism, and exhibit germ-line
      transmission when microinjected into blastocysts. Although germ-cell-specific
      genes were expressed in all culture medium conditions, GSCm did not shift the
      transcriptome towards germ-cell specification. A correlation was further observed
      between ESC derivation efficiency and the expression of some imprinted genes and
      retrotransposable elements. In conclusion, the combination of LIF supplementation
      followed by culture in GSCm establishes a higher efficiency method for ESC
      derivation.

PMID- 24861202
TI  - Sunscreen adherence: proffer patient preference.

PMID- 24861203
TI  - XAV939, a small molecular inhibitor, provides neuroprotective effects on
      oligodentrocytes.
AB  - White matter tracts are composed of axons and myelinating oligodendrocytes.
      Oligodendrocytes are the myelinating cells in the central nervous system that
      allow formation of myelin and saltatory nerve conduction. Cerebral white matter
      is highly vulnerable to ischemic injury in adults and neonates. White matter
      injury in newborn brains results in cerebral palsy and cognitive disability. In
      this study, we found that XAV939, a small-molecular inhibitor that stimulated
      beta-catenin degradation by stabilizing axin, protected against serum and glucose
      deprivation (SGD)-induced cell death in oligodentrocyte cell line OLN-93 cells in
      a concentration-dependent manner. We further showed that XAV939 reduced caspase-3
      and caspase-8 levels and increased the expression of phosphorylated Akt in SGD
      induced OLN-93 cells. Our data demonstrate that XAV939 protects against neonatal
      hypoxic/ischemic injury. In summary, our results demonstrate that XAV939 confers
      neuroprotection against SGD-induced injury in OLN-93 cells via its antiapoptotic
      activity and the loss of oligodendrocytes and neurons in neonatal
      hypoxic/ischemic injury.

PMID- 24861204
TI  - Alpha-phellandrene-induced DNA damage and affect DNA repair protein expression in
      WEHI-3 murine leukemia cells in vitro.
AB  - Although there are few reports regarding alpha-phellandrene (alpha-PA), a natural
      compound from Schinus molle L. essential oil, there is no report to show that
      alpha-PA induced DNA damage and affected DNA repair associated protein
      expression. Herein, we investigated the effects of alpha-PA on DNA damage and
      repair associated protein expression in murine leukemia cells. Flow cytometric
      assay was used to measure the effects of alpha-PA on total cell viability and the
      results indicated that alpha-PA induced cell death. Comet assay and 4,6-diamidino
      2-phenylindole dihydrochloride staining were used for measuring DNA damage and
      condensation, respectively, and the results indicated that alpha-PA induced DNA
      damage and condensation in a concentration-dependent manner. DNA gel
      electrophoresis was used to examine the DNA damage and the results showed that
      alpha-PA induced DNA damage in WEHI-3 cells. Western blotting assay was used to
      measure the changes of DNA damage and repair associated protein expression and
      the results indicated that alpha-PA increased p-p53, p-H2A.X, 14-3-3-sigma, and
      MDC1 protein expression but inhibited the protein of p53, MGMT, DNA-PK, and BRCA
      1.

PMID- 24861205
TI  - Unidirectional barbed suture for vesicourethral anastomosis during laparoscopic
      radical prostatectomy.
AB  - INTRODUCTION: We investigated the impact of unidirectional barbed suture (UBS)
      for vesicourethral anastomosis (VUA) during laparoscopic radical prostatectomy.
      METHODS: The polyglyconate UBS V-Loc 180 was used for VUA during laparoscopic
      radical prostatectomy in 30 consecutive patients who were diagnosed with organ
      confined prostate cancer between January and October 2012. The operative and
      postoperative parameters were then compared with those of 30 consecutive patients
      who had previously undergone the same procedure but with the monofilament
      poliglecaprone suture Monocryl. All procedures were performed by the same
      experienced surgeon. RESULTS: VUA time was significantly shorter in the V-Loc
      group (13.2 +/- 2.3 min) than in the Monocryl group (19.1 +/- 3.3 min) (P <
      0.001). The V-Loc group required significantly more stitches than the Monocryl
      group (11.4 +/- 1.3 vs 10.6 +/- 1.6 stitches; P = 0.031). The percentage of
      patients who required no more than one pad per day at 3 months postoperatively
      was significantly higher in the V-Loc group (63.3%) than in the Monocryl group
      (23.3%) (P = 0.020). No significant differences in other perioperative parameters
      were observed between the two groups. CONCLUSION: Using UBS prevents suture
      slippage and enables tieless anastomosis. VUA using a UBS may relieve surgeon
      stress because a rapid and secure anastomosis is achievable.

PMID- 24861207
TI  - Investigating the interaction of sunset yellow aggregates and 6-fluoro-2
      naphthoic acid: increasing probe molecule complexity.
AB  - The interaction of small molecules with non-covalent assemblies is of wide
      interest. The use of a magnetically active reporter nucleus allows information to
      be obtained in the presence of spectral overlap or in cases of high dynamic
      range. In this paper, we explore the interaction of a larger probe molecule, 6
      fluoro-2-naphthoic acid with assemblies of sunset yellow using (19)F chemical
      shifts and diffusion NMR methods. Comparing the observations with previous
      studies using fluorophenols, 6-fluoro-2-naphthoic acid prefers to associate as
      clusters at the ends of the sunset yellow stacks.

PMID- 24861206
TI  - Heat shock protein 90 promotes epithelial to mesenchymal transition, invasion,
      and migration in colorectal cancer.
AB  - Epithelial to mesenchymal transition (EMT), invasion, and motility are essential
      steps in colorectal cancer (CRC) metastasis regulated by HIF-1alpha and NF
      kappaB. Since HSP90 activates HIF-1alpha and NF-kappaB, we hypothesized that
      inhibition of HSP90 leads to inhibition of HIF-1alpha and NF-kappaB resulting in
      inhibition of EMT, invasion, and motility. Treatment of colorectal cancer cell
      lines HT-29 and HCT-116 with ganetespib at 50 nM for 24 h inhibited EMT
      (downregulated vimentin and upregulated E-cadherin), matrigel invasion, and
      spheroid migration. Ganetespib treatment or HSP90 knockdown downregulated
      molecular pathways associated with EMT, invasion, and motility. The
      overexpression of HIF-1alpha or NF-kappaB resulted in increased EMT, invasion,
      and motility in both cell lines and these effects were inhibited by ganetespib.
      Similar effects were observed in animal xenografts treated with ganetespib. Taken
      together, our data demonstrate for the first time that inhibition of HSP90
      downregulates both HIF-1alpha and NF-kappaB leading to inhibition of EMT,
      motility, and invasiveness in colorectal cancer.

PMID- 24861208
TI  - Slow reactant-water exchange and high catalytic performance of water-tolerant
      Lewis acids.
AB  - (31)P nuclear magnetic resonance (NMR) spectroscopic measurement with
      trimethylphosphine oxide (TMPO) was applied to evaluate the Lewis acid catalysis
      of various metal triflates in water. The original (31)P NMR chemical shift and
      line width of TMPO is changed by the direct interaction of TMPO molecules with
      the Lewis acid sites of metal triflates. [Sc(OTf)3] and [In(OTf)3] had larger
      changes in (31)P chemical shift and line width by formation of the Lewis acid
      TMPO complex than other metal triflates. It originates from the strong
      interaction between the Lewis acid and TMPO, which results in higher stability of
      [Sc(OTf)3TMPO] and [In(OTf)3TMPO] complexes than other metal triflate-TMPO
      complexes. The catalytic activities of [Sc(OTf)3] and [In(OTf)3] for Lewis acid
      catalyzed reactions with carbonyl compounds in water were far superior to the
      other metal triflates, which indicates that the high stability of metal triflate
      carbonyl compound complexes cause high catalytic performance for these reactions.
      Density functional theory (DFT) calculation suggests that low LUMO levels of
      [Sc(OTf)3] and [In(OTf)3] would be responsible for the formation of stable
      coordination intermediate with nucleophilic reactant in water.

PMID- 24861209
TI  - An investigation of the genetic basis of increased susceptibility to
      neutralization by anti-fusion glycoprotein antibody arising on passage of human
      respiratory syncytial virus in cell culture.
AB  - Human respiratory syncytial virus isolates have previously been shown to exhibit
      resistance to neutralization by anti-fusion glycoprotein antibodies that is lost
      on passage in cell culture. Early passage resistant and late passage susceptible
      stocks of two virus isolates from different epidemics were cloned by plaque
      purification. Early passage stocks of both isolates yielded predominantly
      neutralization resistant clones while late passage stocks yielded predominantly
      susceptible clones. On further characterization of resistant and susceptible
      clones, resistant virus yields were lower and they were relatively resistant to
      both neutralization and fusion inhibition by anti-F murine monoclonal antibodies
      and were also resistant to neutralization by human sera and by Palivizumab. The
      full genome of resistant and susceptible clones from one of the isolates was
      sequenced. Four differences, confirmed by sequencing sister clones, were found
      between resistant and susceptible clones, one in each of the SH, G, F, and L
      genes.

PMID- 24861211
TI  - Chemical etching in processing cortical bone specimens for scanning electron
      microscopy.
AB  - Transverse and longitudinal sectioning of undecalcified cortical bone is a
      commonly employed technique for investigating the lamellar structure of the
      osteons. Since a flat surface is required, the specimen has to be grinded and
      then polished. Whereas the smear of debris and inorganic/organic deposits left by
      these treatments cannot be removed by ultrasonication alone, a chemical treatment
      of the specimen surface with either a basic or an acid etching solution is
      currently employed. A further effect of the latter can be the enhancement of the
      lamellar bone pattern. The kind of etching solution, its pH, the concentration of
      etchants, and the contact time significantly affect the sectioned surface when it
      is observed with scanning electron microscopy (SEM). The etching procedures can
      severely influence the obtained images. Homogeneous cortical bone specimens were
      sampled from the first metatarsal of two fresh human subjects. One or two cut
      surfaces were exposed to different acid and basic solutions in bonded conditions.
      Considering the type of chemical agents, the solution pH, and the exposure time
      of the specimens, the effects of several etching media have been investigated and
      compared. Strong etching, either acid or basic produced surface decalcification
      and severe damage of the collagen matrix, compromising any morphological or
      morphometric analysis. Weak acid etching (for example citric and acetic acid),
      even though causing distinctive alteration of the sample, enhanced the visibility
      of the lamellar pattern, while the polyphosphate treatment of the surface
      decalcified a thin layer matrix, ensuring a good visibility of fibrils and
      avoiding rough distortions.

PMID- 24861212
TI  - Predicting vulnerability to sleep deprivation using diffusion model parameters.
AB  - We used diffusion modelling to predict vulnerability to decline in psychomotor
      vigilance task (PVT) performance following a night of total sleep deprivation
      (SD). A total of 135 healthy young adults (69 women, age = 21.9 +/- 1.7 years)
      participated in several within-subject cross-over design studies that
      incorporated the PVT. Participants were classified as vulnerable (lower tertile)
      or non-vulnerable (upper tertile) according to their change in lapse rate [lapse
      = reaction time (RT) >= 500 ms] between the evening before (ESD) and the morning
      after SD. RT data were fitted using Ratcliff's diffusion model. Although both
      groups showed significant change in RT during SD, there was no significant group
      difference in RT during the ESD session. In contrast, during ESD, the mean
      diffusion drift of vulnerable subjects was significantly lower than for non
      vulnerable subjects. Mean drift and non-decision times were both adversely
      affected by sleep deprivation. Both mean drift and non-decision time showed
      significant state * vulnerability interaction. Diffusion modelling appears to
      have promise in predicting vulnerability to vigilance decline induced by a night
      of total sleep deprivation.

PMID- 24861213
TI  - Thiopeptide engineering: a multidisciplinary effort towards future drugs.
AB  - The recent development of thiopeptide analogues of antibiotics has allowed some
      of the limitations inherent to these naturally occurring substances to be
      overcome. Chemical synthesis, semisynthetic derivatization, and engineering of
      the biosynthetic pathway have independently led to complementary modifications of
      various thiopeptides. Some of the new substances have displayed improved
      profiles, not only as antibiotics, but also as antiplasmodial and anticancer
      drugs. The design of novel molecules based on the thiopeptide scaffold appears to
      be the only strategy to exploit the high potential they have shown in vitro.
      Herein we present the most relevant achievements in the production of thiopeptide
      analogues and also discuss the way the different approaches might be combined in
      a multidisciplinary strategy to produce more sophisticated structures. 

PMID- 24861214
TI  - Nitryl cyanide, NCNO2.
AB  - The elusive nitryl cyanide, NCNO2, has been synthesized and characterized. It was
      prepared in good yield, isolated by fractional condensation, characterized by NMR
      and vibrational spectroscopy, and studied by theoretical calculations. Nitryl
      cyanide holds promise as a high energy density material (HEDM) and might also
      prove useful as a HEDM building block. The simplicity and inherent stability of
      nitryl cyanide, together with the known multitude of nitriles in interstellar
      space, suggest that the compound might also be a potential candidate for
      observations in atmospheric and interstellar chemistry.

PMID- 24861210
TI  - Developmental signaling: does it bridge the gap between cilia dysfunction and
      renal cystogenesis?
AB  - For more than a decade, evidence has accumulated linking dysfunction of primary
      cilia to renal cystogenesis, yet molecular mechanisms remain undefined. The
      pathogenesis of renal cysts is complex, involving multiple cellular aberrations
      and signaling pathways. Adding to this complexity, primary cilia exhibit multiple
      roles in a context-dependent manner. On renal epithelial cells, primary cilia act
      as mechanosensors and trigger extracellular Ca(2+) influx in response to laminar
      fluid flow. During mammalian development, primary cilia mediate the Hedgehog
      (Hh), Wnt, and Notch pathways, which control cell proliferation and
      differentiation, and tissue morphogenesis. Further, experimental evidence
      suggests the developmental state of the kidney strongly influences renal cystic
      disease. Thus, we review evidence for regulation of Ca(2+) and cAMP, key
      molecules in renal cystogenesis, at the primary cilium, the role of Hh, Wnt, and
      Notch signaling in renal cystic disease, and the interplay between these
      developmental pathways and Ca(2+) signaling. Indeed if these developmental
      pathways influence renal cystogenesis, these may represent novel therapeutic
      targets that can be integrated into a combination therapy for renal cystic
      disease.

PMID- 24861217
TI  - Graphene-ruthenium complex hybrid photodetectors with ultrahigh
      photoresponsivity.
AB  - The maximum responsivity of a pure monolayer graphene-based photodetector is
      currently less than 10 mA W(-1) because of small optical absorption and short
      recombination lifetime. Here, a graphene hybrid photodetector functionalized with
      a photoactive ruthenium complex that shows an ultrahigh responsivity of ~1 *
      10(5) A W(-1) and a photoconductive gain of ~3 * 10(6) under incident optical
      intensity of the order of sub-milliwatts is reported. This responsivity is two
      orders of magnitude higher than the precedent best performance of graphene-based
      photodetectors under a similar incident light intensity. Upon functionalization
      with a 4-nm-thick ruthenium complex, monolayer graphene-based photodetectors
      exhibit pronounced n-type doping effect due to electron transfer via the metal
      ligand charge transfer (MLCT) from the ruthenium complex to graphene. The
      ultrahigh responsivity is attributed to the long lifetime and high mobility of
      the photoexcited charge carriers. This approach is highly promising for improving
      the responsivity of graphene-based photodetectors. 

PMID- 24861215
TI  - Fibroblastic growth factor receptor 1 amplification in osteosarcoma is associated
      with poor response to neo-adjuvant chemotherapy.
AB  - Osteosarcoma, the most common primary bone sarcoma, is a genetically complex
      disease with no widely accepted biomarker to allow stratification of patients for
      treatment. After a recent report of one osteosarcoma cell line and one tumor
      exhibiting fibroblastic growth factor receptor 1 (FGFR1) gene amplification, the
      aim of this work was to assess the frequency of FGFR1 amplification in a larger
      cohort of osteosarcoma and to determine if this biomarker could be used for
      stratification of patients for treatment. About 352 osteosarcoma samples from 288
      patients were analyzed for FGFR1 amplification by interphase fluorescence in situ
      hybridization. FGFR1 amplification was detected in 18.5% of patients whose tumors
      revealed a poor response to chemotherapy, and no patients whose tumors responded
      well to therapy harbored this genetic alteration. FGFR1 amplification is present
      disproportionately in the rarer histological variants of osteosarcoma. This study
      provides a rationale for inclusion of patients with osteosarcoma in clinical
      trials using FGFR kinase inhibitors. 

PMID- 24861219
TI  - Not all types of host contacts are equal when it comes to E. coli transmission.
AB  - The specific processes that facilitate pathogen transmission are poorly
      understood, particularly for wild animal populations. A major impediment for
      investigating transmission pathways is the need for simultaneous information on
      host contacts and pathogen transfer. In this study, we used commensal Escherichia
      coli strains as a model system for gastrointestinal pathogens. We combined strain
      sharing information with detailed host contact data to investigate transmission
      routes in mountain brushtail possums. Despite E. coli being transmitted via the
      faecal-oral route, we revealed that, strain-sharing among possums was better
      explained by host contacts than spatial proximity. Furthermore, and unexpectedly,
      strain-sharing was more strongly associated with the duration of brief nocturnal
      associations than day-long den-sharing. Thus, the most cryptic and difficult
      associations to measure were the most relevant connections for the transmission
      of this symbiont. We predict that future studies that employ similar approaches
      will reveal the importance of previously overlooked associations as key
      transmission pathways. 

PMID- 24861218
TI  - Hepatitis B surface antigen positivity after twinrix vaccination: a case report.
AB  - Travelers might have an increased risk of hepatitis B virus (HBV) infection. We
      report a case of prolonged transient hepatitis B surface antigenemia in a healthy
      Canadian female 8 days after administration of a combined hepatitis A and
      hepatitis B vaccine. Travel health providers providing hepatitis B vaccines need
      to be aware of this phenomenon and educate their patients accordingly.

PMID- 24861220
TI  - Sucrose favors Pseudomonas aeruginosa pellicle production through the
      extracytoplasmic function sigma factor SigX.
AB  - Pseudomonas aeruginosa biofilm formation was increased by addition of sucrose to
      Luria-Bertani medium, whereas addition of NaCl to a final similar osmolarity and
      use of maltose instead of sucrose, were ineffective. In a previous study, we
      showed that the extracytoplasmic sigma factor SigX is activated in the presence
      of sucrose. The sucrose-mediated pellicle increase was abolished in a sigX mutant
      strain. Sucrose addition led to an increase in pel expression and cyclic
      diguanylate (c-di-GMP) pool level production. Interestingly, these two phenotypes
      were strongly decreased in a sigX mutant. Since pel is not known as a SigX
      target, we suspect SigX to be involved in the c-di-GMP production. We found that
      expression of the diguanylate cyclase PA4843 gene was increased in the presence
      of sucrose at least partly through SigX activity. Our study shows that sucrose
      itself rather than osmolarity favours the biofilm mode of P. aeruginosa through
      the activation of SigX. 

PMID- 24861221
TI  - Study finds new links between number of duplicated genes and adaptation.

PMID- 24861222
TI  - [Cost-effectiveness of buccal midazolam in the treatment of prolonged convulsive
      seizures in the outpatient setting in Spain].
AB  - INTRODUCTION: To be able to treat prolonged epileptic crises practical, safe and
      effective rescue medication is needed. Today, the standard treatment in community
      healthcare is rectal diazepam. The introduction of a buccal solution of midazolam
      opens up a new perspective in their treatment. AIMS: To evaluate the cost
      effectiveness of buccal midazolam with respect to rectal diazepam for children
      diagnosed with epilepsy who present prolonged convulsive seizures in the
      community setting in Spain. MATERIALS AND METHODS: The study produces a model of
      its cost-effectiveness from the perspective of the Spanish National Health System
      (SNS), with the outcomes presented in terms of cost-quality adjusted life years.
      Data were collected from different sources, including estimations regarding the
      clinical effectiveness from a clinical trial, from a Delphi panel in Spain and
      from a national survey carried out on parents of children with epilepsy in order
      to determine the current practices. RESULTS: Treatment with buccal midazolam
      produces a saving in costs in comparison to rectal diazepam. The amount saved by
      the Spanish SNS comes to 5,484 euros per patient per year. Treatment with buccal
      midazolam offers an improved health-related quality of life. This, together with
      the savings in costs, means that there is a dominance of buccal midazolam over
      rectal diazepam in all the settings that have been examined. CONCLUSIONS: The
      results obtained with the model show that buccal midazolam is more cost-effective
      than rectal diazepam due to a reduction in the need to call out ambulances and
      for stays in hospital, as well as an improved health-related quality of life.

PMID- 24861223
TI  - [Referrals from primary care to a dedicated headache clinic: analysis of the
      first 1,000 patients].
AB  - INTRODUCTION: It is commonplace practice in dedicated clinics or headache units
      to deal with complex patients referred from general neurology clinics. In our
      centre, part of the schedule of the dedicated headache clinic (DHC) is reserved
      for patients referred from primary care (PC) in the form of one-stop clinics.
      AIMS: To analyse both the characteristics of the patients referred by PC to DHC
      and the suitability of the agreed referral criteria, and to compare them with the
      first visits due to headache in a general neurology clinic. PATIENTS AND METHODS:
      The study was conducted on a sample of 1,000 patients (741 females and 259 males)
      in the DHC and 290 (203 females and 87 males) in the general clinic. Data were
      collected retrospectively and included demographic variables, previous use of
      symptomatic or preventive treatments, need for complementary examinations and
      adjustment to referral criteria. Headaches were coded in accordance with the
      second edition of the International Headache Classification (IHC-2). RESULTS: A
      total of 1,562 headaches were coded in the DHC group and 444 in the general
      clinic group; their distribution over the groups of the IHC-2 was similar, and
      most of them fell into group 1 (migraine). The percentage of patients who had
      received preventive treatment was higher in the DHC. The percentage of
      appropriate referrals was high and a little higher still in the general clinic.
      CONCLUSIONS: The characteristics of the patients referred from PC to a DHC in our
      milieu were similar to those reported in previous studies. These patients have
      received treatment more frequently than those who were seen in a general
      neurology clinic.

PMID- 24861224
TI  - [Semantic verbal fluency of animals in amnesia-type mild cognitive impairment].
AB  - INTRODUCTION AND AIM: The quantitative and qualitative analysis of the semantic
      verbal fluency task has revealed that people with dementia produced fewer words
      and smaller semantic clustering than people without dementia. However, in people
      with amnestic mild cognitive impairment (aMCI), research has shown conflicting
      results regarding the amount and number of semantic clusters that are made. The
      aim of this study was to provide new data to this controversial issue. SUBJECTS
      AND METHODS: Twenty-two older adults diagnosed with aMCI (8 men and 14 women) and
      43 older adults (7 men and 36 women) with normal cognitive functioning that
      served as control group, participated in this study. All patients were evaluated
      at the Center for Prevention of Cognitive Decline of Madrid (Spain), completing
      the verbal fluency test (animals) besides other neuropsychological tests.
      RESULTS: As expected, animal production was lower in the aMCI group than in the
      control group, but no differences were observed either in the average size of the
      semantic clusters or the number of switches between them. CONCLUSIONS: The
      results are consistent with previous research suggesting aMCI is not only
      characterized by episodic memory and working memory deficits. Semantic memory
      decline is also present. However, the data do not clarify how strategic executive
      processes are involved, as seems to be in Alzheimer's disease.

PMID- 24861225
TI  - [Psychosis as debut of antiphospholipid syndrome].
AB  - INTRODUCTION: Antiphospholipid syndrome (APS) is an autoimmune disorder which
      causes an hypercoagulation state characterized by thrombotic events, repetitive
      miscarriages and the presence of antiphospholipid antibodies. APS may be an
      isolated disease (primary APS) or associated to systemic lupus erythematous or
      another autoimmune conditions (secondary APS). Neuropsychiatric manifestations
      accompanying APS include migraine, epilepsy, chorea, dementia or psychosis.
      Detailed descriptions of clinical cases are lacking, and correlations between
      clinical and analytical findings are far from being well known. We review
      literature concerning neuropsychiatric manifestations in general and psychosis in
      particular, in patients suffering from AFS. CASE REPORT: A 23 years-old female
      who presented a primary AFS with a clinical debut consisting of neuropsychiatric
      manifestations characterized by psychosis (with two delusion episodes) and
      abnormal movements such as choreiform and hemiballistic movements, initially
      understood as conversive symptoms. CONCLUSIONS: We discuss the pathogenesis of
      the psychotic and motor manifestations. The etiology is nowadays not completely
      understood, but cerebral small vessel thrombosis might explain part of the
      manifestations. We also review the role of antipsychotic and antithrombotic
      medication for these patients. Currently, our patient remains asymptomatic
      without any antipsychotic agent, only being treated with antiagregant and
      antipalludic therapy.

PMID- 24861227
TI  - [Marchiafava-Bignami disease].

PMID- 24861226
TI  - [Management of complications related to intraduodenal infusion of
      levodopa/carbidopa in patients with Parkinson's disease].
AB  - Continuous infusion of intraduodenal levodopa/carbidopa is an effective treatment
      that improves the motor complications and the quality of life of patients in the
      advanced stages of Parkinson's disease. However, it is not free of complications.
      These may present in the post-operative period following surgery (gastrostomy) or
      in the long-term during the follow-up period and can be related with the
      medication (levodopa/carbidopa), the stoma, the gastrostomy or the device (pump,
      enteral tube, parts of the FREKA system). The aim of this review is to report on
      the management of the complications that can be observed in patients with
      advanced Parkinson's disease treated with continuous infusion of intraduodenal
      levodopa/carbidopa. 

PMID- 24861229
TI  - [Migration of the distal catheter of a ventriculoperitoneal shunt into the
      heart].

PMID- 24861230
TI  - [Spontaneous extradural spinal haematoma].

PMID- 24861231
TI  - [Neuropsychological rehabilitation in wartime].

PMID- 24861232
TI  - Impact of donor kidney function and donor age on poor outcome of living-unrelated
      kidney transplantation (KT) in comparison with living-related KT.
AB  - Living-unrelated donors (LURD) have been widely used for kidney transplantation
      (KT). We retrospectively reviewed 779 patients who underwent living-donor KT from
      2000 to 2012, to compare outcomes of 264 KT from LURD and 515 from living-related
      donors (LRD), and to identify risk factors for living KT. Median follow-up was 67
      months. Mean donor age, total human leukocyte antigen (HLA) mismatches, and HLA
      DR mismatches were higher, and mean estimated glomerular filtration rate (eGFR)
      was lower in LURD. Acute rejection (AR)-free survival (p = 0.018) and graft
      survival (p = 0.025) were lower for LURD than LRD, whereas patient survival rate
      was comparable. Cox regression analysis showed HLA-DR mismatches (OR 1.75 for one
      mismatch; OR 2.19 for two mismatches), recipient age <= 42 yr, and donor age > 50
      yr were significant risk factors for acute rejection. For graft survival, AR and
      donor eGFR (OR 1.90, p = 0.035) were significant. We also identified significant
      impact of recipient age > 50 yr and diabetes for patient survival. However, KT
      from LURD was not a significant risk factor for AR (p = 0.368), graft survival (p
      = 0.205), and patient survival (p = 0.836). Our data suggest that donor eGFR and
      donor age are independent risk factors for clinical outcomes of living KT, which
      can be related with poor outcome of KT from LURD. 

PMID- 24861233
TI  - Development of multiplex pyrosequencing for HLA-B*57:01 screening using single
      nucleotide polymorphism haplotype.
AB  - WHAT IS KNOWN AND OBJECTIVE: Abacavir (ABC) is a commonly used nucleoside reverse
      transcriptase inhibitor with potent antiviral activity against HIV-1. The US Food
      and Drug Administration and international HIV treatment guidelines recommend HLA
      B*57:01 screening before initiating treatment with ABC. The current standard
      method for HLA-B*57:01 screening is limited by its high-cost, time-consuming and
      labour-intensive procedure with the requirement of a specialized laboratory. Our
      study aims to develop a more reliable screening test by selecting rs3093726 as an
      additional single nucleotide polymorphism (SNP) to combine with rs2395029 for
      multiplex pyrosequencing development. It offers high-accuracy, cost-effective and
      rapid detection. METHODS: Multiplex pyrosequencing was developed for HLA-B*57:01
      screening using rs2395029 and rs3093726 as a surrogate marker and tested in 130
      Thai subjects in parallel with singleplex pyrosequencing of each SNP and the
      standard sequence-based method. RESULTS AND DISCUSSION: Multiplex pyrosequencing
      showed 100% concordance when compared with both singleplex pyrosequencing and
      standard sequence-based method. This method showed 100% of negative predictive
      value (NPV), positive predictive value (PPV), specificity and sensitivity. WHAT
      IS NEW AND CONCLUSION: Multiplex pyrosequencing is a powerful tool for HLA
      B*57:01 screening using the rs2395029 and rs3093726 haplotype genotyping as
      surrogate marker for this HLA-B. The assay provides accurate, cost-effective and
      rapid detection of this haplotype. It can be applied for ABC hypersensitivity
      screening of the Thai population before initiating treatment with ABC.

PMID- 24861234
TI  - Cut us some slack.

PMID- 24861235
TI  - Cross-sectional imaging of nontraumatic emergencies of the spleen.
AB  - Multiple nontraumatic splenic emergencies are encountered during the imaging of
      patients in emergency room. Occasionally, patients are investigated for symptoms
      of suspected splenic pathology, such as abscess, infarct, symptomatic splenic
      artery aneurysm and pseudoaneurysm, splenic torsion, or rupture. More often,
      however, splenic emergencies, such as splenic masses and splenic vein thrombosis,
      are detected in patients in the emergency room during the evaluation of
      nonspecific abdominal pain. It is essential for radiologists to be vigilant in
      the identification of nontraumatic splenic emergencies and to be familiar with
      interventional radiology management options for these pathologies. Our aim is to
      highlight factors affecting lesion detection on multiple imaging modalities and
      to discuss the advantages of different cross-sectional modalities for the
      diagnosis of splenic abnormalities. Finally, we review the management options
      with emphasis on interventional radiology where applicable. 

PMID- 24861236
TI  - Using family sculpting as an experiential learning technique to develop
      supportive care in nursing. A contemporary issue paper.
AB  - This article explores the use of family sculpting as an educative tool to achieve
      a better I-thou awareness of the patient's support needs from a family and social
      system approach. Ensuring we provide appropriate and effective opportunities for
      nurses to develop compassion when caring for patients facing ill health is a
      complex challenge that faces nurse education at all levels. The piece explores a
      sculpting exercise developed in nurse education which engages students' awareness
      of the complicated nature of peoples' social networks and through attitudinal
      learning, helps nurses to provide compassionate care that integrates family
      support. 

PMID- 24861237
TI  - New approach to 'top-and-bottom' whole blood separation using the multiunit TACSI
      WB system: quality of blood components.
AB  - BACKGROUND AND OBJECTIVES: TACSI whole blood system is designed to combine
      primary and secondary processing of six whole blood bags into plasma units, buffy
      coat and red blood cell concentrates. The aim of this study was to investigate
      the specifications and in vitro storage parameters of blood components compared
      with standard centrifugation and separation processing. MATERIALS AND METHODS:
      Whole blood bags, collected in CRC kits, were treated on a TACSI whole blood
      system. They were compared with whole blood bags collected in Composelect kits.
      In addition to routine quality control analyses, conservation studies were
      performed on red blood cell concentrates for 42 days and on plasma for 6 months.
      Platelets pools with five buffy coats were also created, and cellular
      contamination was evaluated. RESULTS: Red blood cell concentrates produced from
      TACSI whole blood met European quality requirements. For white blood cell count,
      one individual result exceeded 1 * 10(6) cells/unit. All plasma units fell within
      specifications for residual cellular contamination and storage parameters. The
      performances of the TACSI whole blood system allow for the preparation of low
      volume buffy coats with a recovery of 90% of whole blood platelets. Haemoglobin
      losses in TACSI BC are smaller, but this did not result in higher haemoglobin
      content of red cells. These BC are suitable for the production of platelet
      concentrates. CONCLUSION: From these in vitro data, red blood cell concentrates
      produced using TACSI whole blood are suitable for clinical use with a quality at
      least equivalent to the control group.

PMID- 24861239
TI  - Temporal dynamics of pore water concentrations of Cd, Co, Cu, Ni, and Zn and
      their controlling factors in a contaminated floodplain soil assessed by
      undisturbed groundwater lysimeters.
AB  - We aimed to assess the dynamics of pore water concentrations of Cd, Co, Cu, Ni,
      Zn and their controlling factors (EH, pH, DOC, Fe, Mn, and SO4(2-)) in a
      contaminated floodplain soil under different flood-dry-cycles. Two parallel
      undisturbed groundwater lysimeters (mean values presented) were used for long
      term (LT; 94 days) and short term (ST; 21 days) flood-dry-cycles. Reducing
      conditions under LT lead to low EH and pH, while DOC, Co, Fe, Mn, and Ni
      increased. Cadmium, Cu, Zn, and SO4(2-) increased under oxidizing conditions
      during ST. Cobalt and Ni revealed a similar behavior which seem to governed by
      EH/pH, Mn, Fe, and DOC. Cadmium, Cu, and Zn reveal a similar fate; their dynamics
      were affected by EH/pH, DOC, and SO4(2-). Our findings suggest that a release of
      Cd, Cu, Co, Fe, Mn, Ni, and Zn under different flood-dry-cycles can assumed what
      might create potential environmental risks in using metal-enriched floodplain
      soils. 

PMID- 24861238
TI  - Ozone and ozone injury on plants in and around Beijing, China.
AB  - Ozone (O3) levels were assessed for the first time with passive samplers at 10
      sites in and around Beijing in summer 2012. Average O3 concentrations were higher
      at locations around Beijing than in the city center. Levels varied with site
      locations and ranged from 22.5 to 48.1 ppb and were highest at three locations.
      Hourly O3 concentrations exceeded 40 ppb for 128 h and 80 ppb for 17 h from 2 to
      9 in August at one site, where it had a real-time O3 analyzer. Extensive foliar
      O3 injury was found on 19 species of native and cultivated trees, shrubs, and
      herbs at 6 of the 10 study sites and the other 2 sites without passive sampler.
      This is the first report of O3 foliar injury in and around Beijing. Our results
      warrant an extensive program of O3 monitoring and foliar O3 injury assessment in
      and around Beijing. 

PMID- 24861240
TI  - Virtue ethics and nursing: on what grounds?
AB  - Within the nursing ethics literature, there has for some time now been a focus on
      the role and importance of character for nursing. An overarching rationale for
      this is the need to examine the sort of person one must be if one is to nurse
      well or be a good nurse. How one should be to live well or live a/the good life
      and to nurse well or be a good nurse seems to necessitate a focus on an agent's
      character as well as actions because character is (for the most part) expressed
      in action (e.g. see Laird). This paper will give an overview of the reasons for
      the role and importance of character in nursing practice and explain its relation
      to nursing's frequent use of virtue ethics in order to recommend caution. While
      the paper agrees that the role of character is important in nursing caution is
      needed in both how much moral and thus normative, emphasis is being placed on the
      psychology of character and on the drift to virtue ethics. The psychological
      which may be explanatory needs to be linked with the normative, and a
      justification for the normative is needed. A justification as virtue ethics is
      contested, and nursing practice does not need to take on this explanatory and
      justificatory burden. A tentative proposal raised but not discussed in depth in
      this paper is that when an ultimate explanation or explanatory ground is needed,
      nursing practice leads quite naturally to a form of consequentialism as well as a
      realist metaethic. On this account, there are two levels of moral thinking, and
      nursing practice entails the virtues at one level and leads quite naturally to
      moral thinking at another more critical level of the criterion of what makes
      something right and good independently of character. 

PMID- 24861241
TI  - Environmentally driven evolution of Rubisco and improved photosynthesis and
      growth within the C3 genus Limonium (Plumbaginaceae).
AB  - Carbon assimilation by most ecosystems requires ribulose-1,5-bisphosphate
      carboxylase/oxygenase (Rubisco). Its kinetic parameters are likely to have
      evolved in parallel with intracellular CO2 availability, with the result that
      faster forms of Rubisco occur in species with CO2 -concentrating mechanisms. The
      Rubisco catalytic properties were determined and evaluated in relation to growth
      and carbon assimilation capacity in Mediterranean Limonium species, inhabiting
      severe stress environments. Significant kinetic differences between closely
      related species depended on two amino acid substitutions at functionally
      important residues 309 and 328 within the Rubisco large subunit. The Rubisco of
      species facing the largest CO2 restrictions during drought had relatively high
      affinity for CO2 (low Michaelis-Menten constant for CO2 Kc) but low maximum rates
      of carboxylation (kcatc), while the opposite was found for species that
      maintained higher CO2 concentrations under similar conditions. Rubisco kinetic
      characteristics were correlated with photosynthetic rate in both well-watered and
      drought-stressed plants. Moreover, the drought-mediated decrease in plant biomass
      accumulation was consistently lower in species with higher Rubisco carboxylase
      catalytic efficiency (kcatc/Kc). The present study is the first demonstration of
      Rubisco adaptation during species diversification within closely related C3
      plants, revealing a direct relationship between Rubisco molecular evolution and
      the biomass accumulation of closely related species subjected to unfavourable
      conditions.

PMID- 24861242
TI  - Distinct subcellular localization of the neuronal marker HuC/D reveals hypoxia
      induced damage in enteric neurons.
AB  - BACKGROUND: Correct neuronal identification is essential to study neurons in
      health and disease. Although commonly used as pan-neuronal marker, HuC/D's
      expression pattern varies substantially between healthy and (patho)physiological
      conditions. This heterogenic labeling has received very little attention. We
      sought to investigate the subcellular HuC/D localization in enteric neurons in
      different conditions. METHODS: The localization of neuronal RNA-binding proteins
      HuC/D was investigated by immunohistochemistry in the mouse myenteric plexus
      using different toxins and caustic agents. Preparations were also stained with
      Sox10 and glial fibrillary acidic protein (GFAP) antibodies to assess enteric
      glial cell appearance. KEY RESULTS: Mechanically induced tissue damage,
      interference with the respiratory chain and oxygen (O2 ) deprivation increased
      nuclear HuC/D immunoreactivity. This effect was paralleled by a distortion of the
      GFAP-labeled glial network along with a loss of Sox10 expression and coincided
      with the activation of a non-apoptotic genetic program. Chemically induced damage
      and specific noxious stimuli did not induce a change in HuC/D immunoreactivity,
      supporting the specific nature of the nuclear HuC/D localization. CONCLUSIONS &
      INFERENCES: HuC/D is not merely a pan-neuronal marker but its subcellular
      localization also reflects the condition of a neuron at the time of fixation. The
      functional meaning of this change in HuC/D localization is not entirely clear,
      but disturbance in O2 supply in combination with the support of enteric glial
      cells seems to play a crucial role. The molecular consequence of changes in HuC/D
      expression needs to be further investigated.

PMID- 24861244
TI  - Persistent left cranial vena cava draining into the left atrium associated with
      pulmonary stenosis in a French bulldog.
AB  - A 5-month-old female French bulldog was evaluated for the presence of a heart
      murmur. Through clinical and echocardiographic evaluations, a severe Type A
      pulmonary stenosis was diagnosed. Angiography during right ventricular
      catheterization for valvuloplasty revealed drainage from a persistent left
      cranial vena cava (PLCVC) into the left atrium; this was confirmed later by
      contrast echocardiography. This report is the first to describe this anatomical
      variant of a PLCVC in a dog. 

PMID- 24861243
TI  - Polarization gating spectroscopy of normal-appearing duodenal mucosa to detect
      pancreatic cancer.
AB  - BACKGROUND: According to the field effect theory, by detecting microvasculature
      changes such as early increase in blood supply (EIBS) in the surrounding tissue,
      neoplastic lesions can be identified from a distance. OBJECTIVE: To determine the
      feasibility and efficacy of a fiberoptic probe containing novel polarization
      gating spectroscopy technology to identify patients with pancreatic
      adenocarcinoma (PAC) by the field effect theory. DESIGN: Prospective cohort
      (pilot) study. SETTING: Outpatient tertiary care center. PATIENTS: Adult (>= 18
      years) patients undergoing EGD-EUS were screened. Patients with PAC were included
      in the "cancer" group and patients without PAC were included in the "control"
      group. We excluded patients with other known malignancies and gastroduodenal
      premalignant lesions. INTERVENTIONS AND MAIN OUTCOME MEASURES: Spectroscopic
      measurements of EIBS variables, such as deoxyhemoglobin concentration (DHb) and
      mean blood vessel radius (BVR), were obtained from 5 periampullary locations. The
      Mann-Whitney rank sum test was used for the statistical analysis (P <= .05).
      RESULTS: Fourteen patients (mean age 72 years, 79% male) in the cancer group and
      15 patients (mean age 63 years, 60% male) in the control group were included in
      the final analysis. At the ampullary site, both DHb (P = .001) and BVR (P = .03)
      were higher in PAC patients than in the control subjects. The DHb alone (92%
      sensitivity, 86% specificity) or in combination with BVR (92% sensitivity, 79%
      specificity) can differentiate PAC from control subjects with high accuracy.
      LIMITATIONS: Small sample size, unmatched control subjects. CONCLUSIONS:
      Spectroscopic measurements of EIBS by fiberoptic probes are feasible. Preliminary
      evidence suggests that in vivo measurement of normal-appearing duodenal tissue
      can differentiate PAC patients from a distance with high accuracy.

PMID- 24861245
TI  - Clinical and microbiological findings in prosthetic joint replacement due to
      aseptic loosening.
AB  - OBJECTIVES: A role for microorganisms in aseptic prosthetic loosening (AL) is
      postulated. We analyse the microbiological and clinical findings of patients with
      suspected AL, and compare them with patients with chronic prosthetic joint
      infection (PJI). METHODS: Prospective study (2011-2012) of patients with presumed
      AL. Evaluation of tissue samples (>=5; TS) at the time of surgery and sonication
      fluid (SF) of prosthesis. RESULTS: According to positive culture in TS/SF, 89
      patients were divided into: Group1: (>=2 positive-TS; n = 12); Group2: single
      positive-TS and concordant SF (n = 10); Group3: one positive or non-concordant TS
      or SF (n = 38); and Group4: cultures negative (n = 29). Positive-SF was always
      concordant with TS in Group 1 (75%); it was positive in 74% in Group 3. Median
      months (prosthesis-age: implantation to revision arthroplasty) for PJI and Group
      1-4 was 21, 46, 65, 63 and 81, respectively (P < 0.001); they also had a
      different dynamic trend in prosthesis failure (P < 0.001). CONCLUSIONS: Several
      patients with suspected AL are misdiagnosed PJI. Results from SF correlated well
      with TS in Group 1, led us to consider single positive-TS as significant (Group
      2) and to suggest that microorganisms were on the prosthesis (Group 3). We
      observed a correlation between microbiology and prosthesis-age, which supports
      that early loosening is more often caused by hidden PJI than late loosening.

PMID- 24861246
TI  - Which imaging technique should we use in the follow up of gynaecological cancer?
AB  - Follow-up routines after gynaecological cancer vary. The optimal approach is
      unknown, and no randomised-controlled trials comparing surveillance protocols
      have been published. In this chapter, we summarise the diagnostic performance of
      ultrasound, computed tomography, and magnetic resonance imaging in the follow up
      of women treated for ovarian or uterine cancers. Computed tomography is today the
      standard imaging method for the follow up of women treated for endometrial,
      cervical, or ovarian cancer. Six-monthly or annual follow-up examinations have
      not been shown to positively affect survival. Instead, a combination of
      transvaginal and transabdominal ultrasound examination with clinical examination
      might be a more cost-effective strategy for early detection of recurrence.
      Positron-emission tomography might play a role in women with clinical or
      serological suspicion of recurrence but without evidence of disease at
      conventional diagnostic imaging. To create guidelines, more studies, preferably
      randomised-controlled trials, on follow-up strategies are needed. 

PMID- 24861247
TI  - Imaging for the evaluation of endometriosis and adenomyosis.
AB  - Endometriosis affects between 5 and 45% of women in reproductive age, is
      associated with significant morbidity, and constitutes a major public health
      concern. The correct diagnosis is fundamental in defining the best treatment
      strategy for endometriosis. Therefore, non-invasive methods are required to
      obtain accurate diagnoses of the location and extent of endometriotic lesions.
      Transvaginal sonography and magnetic resonance imaging are used most frequently
      to identify and characterise lesions in endometriosis. Subjective impression by
      an experienced sonologist for identifying endometriomas by ultrasound showed a
      high accuracy. Adhesions can be evaluated by real-time dynamic transvaginal
      sonography, using the sliding sign technique, to determine whether the uterus and
      ovaries glide freely over the posterior and anterior organs and tissues.
      Diagnosis is difficult when ovarian endometriomas are absent and endometriosis
      causes adhesions and deep infiltrating nodules in the pelvic organs. Magnetic
      resonance imaging seems to be useful in diagnosing all locations of
      endometriosis, and its diagnostic accuracy is similar to those obtained using
      ultrasound. Transvaginal ultrasound has been proposed as first line-line imaging
      technique because it is well accepted and widely available. The main limitation
      of ultrasound concerns lesions located above the rectosigmoid junction owing to
      the limited field-of-view of the transvaginal approach and low accuracy in
      detecting upper bowel lesions by transabdominal ultrasound. A detailed non
      invasive diagnosis of the extension in the pelvis of endometriosis can facilitate
      the choice of a safe and adequate surgical or medical treatment. 

PMID- 24861248
TI  - Imaging techniques for the evaluation of cervical cancer.
AB  - Improvements in the treatment of cervical carcinoma have made it possible to
      offer optimal and personalised treatment. Cervical cancer staging is based on
      clinical examination and histological findings. Many diagnostic methods are used
      in clinical practice. Magnetic resonance imaging is considered the optimal method
      for staging cervical carcinoma because of its high accuracy in assessing local
      extension of disease and distant metastases. Ultrasound has gained increased
      attention in recent years; it is faster, cheaper, and more widely available than
      other imaging techniques, and is highly accurate in detecting tumour presence and
      evaluating local extension of disease. Magnetic resonance imaging and ultrasound
      are often used together with computed tomography or positron emission tomography
      combined with computed tomography to assess the whole body, a more accurate
      detection of pathological lymph nodes and metabolic information of the disease. 

PMID- 24861249
TI  - EWS/FLI-l peptide-pulsed dendritic cells induces the antitumor immunity in a
      murine Ewing's sarcoma cell model.
AB  - An increasing number of T-cell epitopes derived from various tumor-associated
      antigens have been reported, and they proved to play significant roles for tumor
      rejection both in vivo and in vitro. Over 85% of Ewing's sarcoma family of tumors
      (ESFTs) express tumor-specific chimeric protein EWS/FLI-1, making it an
      attractive target for therapeutic cytotoxic T-lymphocyte responses. Here, we
      identified a novel peptide epitope derived from the EWS/FLI-1 protein and
      demonstrated that effectors induced by the peptide could specifically secrete IFN
      gamma and lyse the tumor cell line of EWS/FLI-1-positive and HLA-matched cells.
      In addition, mice treated with dendritic cells pulsed with the EWS/FLI-1 epitope
      were able to reject a lethal tumor inoculation of the Ewing's sarcoma A673 cells.
      Therefore, these data provide evidence for the use of the EWS/FLI-l peptide
      epitope in T cell-based immunotherapeutic concepts against Ewing's sarcoma cell
      in vitro and in vivo.

PMID- 24861251
TI  - The novel role of thymopentin in induction of maturation of bone marrow dendritic
      cells (BMDCs).
AB  - Thymopentin is an immune-modulating peptide that can stimulate cellular immune
      responses and has been used in many immune handicapped cases [1]. However,
      despite documented reports proving its efficacy in immunoregulation, there have
      been no reports, as yet, concerning its impact on the maturation and function of
      dendritic cells (DCs). In this study, we analyzed the effects of thymopentin on
      the detailed regulation of maturation of murine bone-marrow-derived DCs (BMDCs).
      The phenotypic and structural maturation of BMDCs was confirmed by transmission
      electron microscopy (TEM) and flow cytometry (FCM). The functional maturation was
      confirmed by an acid phosphatase (ACP) activity test, FITC-dextran bio-assay,
      test of 5,6-carboxyfluorescein diacetate succinimidyl ester (CFSE), labeled
      CD4(+)T cell proliferation and enzyme-linked immunosorbent assay (ELISA). We
      determined that thymopentin up-regulated the expression of CD40, CD80, CD86,
      CD83, and MHC II molecules on BMDCs, down-regulated phagocytosis of BMDCs,
      increased BMDCs driven CD4(+)T cell proliferation, and enhanced BMDC production
      of IL-12 and TNF-alpha. Therefore, we concluded that thymopentin highly induces
      BMDC maturation and intensifies DC/T-cell pathways. These data also provide
      direct evidence and rationale concerning the potential clinical use of
      thymopentin in various immune handicapped cases and suggest that thymopentin
      should be considered as a potent adjuvant for DC-based vaccines. 

PMID- 24861250
TI  - Protective effect of SKLB010 against D-galactosamine/lipopolysaccharide-induced
      acute liver failure via nuclear factor-kappaB signaling pathway in macrophages.
AB  - Acute liver failure is characterized by the sudden loss of hepatic function and a
      high mortality. SKLB010, a derivative of thiazolidinediones, has been proved to
      be effective in protecting mice from acute liver failure caused by concanavalin A
      and carbon tetrachloride in our previous work. The purpose of the current study
      was to evaluate whether SKLB010 could prevent acute liver injury caused by d
      galactosamine/lipopolysaccharide (LPS) in mice, and to investigate the underlying
      mechanisms. In the macrophage-mediated D-GalN/LPS model of acute liver injury,
      serum enzyme activity was suppressed and liver injury was attenuated by SKLB010.
      The serum levels of TNF-alpha and hepatic TNF-alpha mRNA expression were also
      markedly decreased after the treatment of SKLB010. In the liver of mice receiving
      injections of D-GalN/LPS, hepatocytes apoptosis and the infiltration of
      monocytes/macrophages were blocked by SKLB010. Furthermore, the survival rate of
      mice following D-GalN/LPS treatment was significantly improved by a single
      injection with SKLB010. In vivo, the luminescence intensity was suppressed by
      SKLB010 in NF-kappaB-luc mice after D-GalN/LPS treatment. In vitro, the
      production of tumor necrosis factor (TNF)-alpha and nitrite/nitrate in LPS
      stimulated RAW264.7 macrophages was decreased by SKLB010 in a dose-dependent
      manner. Our further studies demonstrated that SKLB010 inhibited the
      phosphorylation of IkappaBalpha and p38MAPK, and the DNA binding activity of NF
      kappaB in RAW264.7 cells. In conclusion, treatment with only a single injection
      of SKLB010 could significantly attenuate acute inflammation in mice induced by D
      GalN/LPS, and these effects are likely associated with the inhibition of NF
      kappaB activity. 

PMID- 24861252
TI  - Bullous pemphigoid induced by vildagliptin: a report of three cases.
AB  - To report three cases of bullous pemphigoid in patients treated with
      vildagliptin. Case 1: An 86-year-old woman presented with bullous pemphigoid
      after 1 month of treatment with vildagliptin and metformin. After introduction of
      clobetasol, the symptoms resolved although vildagliptin was continued. However,
      the skin lesions reappeared 3 months later. Sustained remission was achieved only
      after definitive withdrawal of vildagliptin. Case 2: A 79-year-old man presented
      with bullous pemphigoid after 37-month treatment with gliclazide, vildagliptin
      and metformin. The disease at first responded to clobetasol but 3 months later
      the lesions reappeared. They finally regressed when the gliptin was discontinued.
      Case 3: A 77-year-old woman, treated with gliclazide and vildagliptin for 26
      months, presented with bullous pemphigoid, which responded well to
      discontinuation of the gliptin and topical clobetasol. Gliptins are new molecules
      for treatment of type 2 diabetes mellitus, which have been suspected of
      implication in bullous pemphigoid. Such cases have been described in the
      literature (seven with vildagliptin and three with sitagliptin). In nine of these
      cases, the gliptin was associated with metformin, but the latter had never been
      considered responsible. The mechanism implicated in the development of bullous
      pemphigoid has not yet been clearly identified, but may involve a modified immune
      response or alteration of the antigenic properties of the epidermal basement
      membrane. These reports support the risk of bullous pemphigoid in patients
      exposed to gliptins. 

PMID- 24861253
TI  - Coronary embolization following electrical cardioversion in a patient treated
      with dabigatran.

PMID- 24861254
TI  - Current challenges for clinical trials of cardiovascular medical devices.
AB  - Several features of cardiovascular devices raise considerations for clinical
      trial conduct. Prospective, randomized, controlled trials remain the highest
      quality evidence for safety and effectiveness assessments, but, for instance,
      blinding may be challenging. In order to avoid bias and not confound data
      interpretation, the use of objective endpoints and blinding patients, study
      staff, core labs, and clinical endpoint committees to treatment assignment are
      helpful approaches. Anticipation of potential bias should be considered and
      planned for prospectively in a cardiovascular device trial. Prospective, single
      arm studies (often referred to as registry studies) can provide additional data
      in some cases. They are subject to selection bias even when carefully designed;
      thus, they are generally not acceptable as the sole basis for pre-market approval
      of high risk cardiovascular devices. However, they complement the evidence base
      and fill the gaps unanswered by randomized trials. Registry studies present
      device safety and effectiveness in day-to-day clinical practice settings and
      detect rare adverse events in the post-market period. No single research design
      will be appropriate for every cardiovascular device or target patient population.
      The type of trial, appropriate control group, and optimal length of follow-up
      will depend on the specific device, its potential clinical benefits, the target
      patient population and the existence (or lack) of effective therapies, and its
      anticipated risks. Continued efforts on the part of investigators, the device
      industry, and government regulators are needed to reach the optimal approach for
      evaluating the safety and performance of innovative devices for the treatment of
      cardiovascular disease. 

PMID- 24861255
TI  - Spontaneous coronary artery dissection.
AB  - Spontaneous coronary artery dissection (SCAD) is a relatively rare and unexplored
      type of coronary disease. Although atherosclerosis, hormonal changes during
      pregnancy and connective tissue disorders might represent a sufficiently
      convincing explanation for some patients with SCAD, the many remaining cases
      display only a weak relationship with these causes. While on one side the
      clinical heterogeneity of SCAD masks a full understanding of their underlying
      pathophysiologic process, on the other side paucity of data and misleading
      presentations hamper the quick diagnosis and optimal management of this
      condition. A definite diagnosis of SCAD can be significantly facilitated by
      endovascular imaging techniques. In fact, intravascular ultrasound (IVUS) and
      optical coherence tomography (OCT) overcome the limitations of coronary
      angiography providing detailed endovascular morphologic information. In contrast,
      optimal treatment strategies for SCAD still represent a burning controversial
      question. Herein, we review the published data examining possible causes and
      investigating the best therapy for SCAD in different clinical scenarios. 

PMID- 24861256
TI  - Safety and feasibility of iliac endovascular interventions with a radial
      approach. Results from a multicenter study coordinated by the Italian Radial
      Force.
AB  - BACKGROUND: Percutaneous angioplasty of lower limb disease is commonly performed
      with a transfemoral access. In the coronary field, a transradial approach has
      shown to reduce access-site bleeding and adverse clinical events. This route has
      not yet been well studied for the majority of peripheral interventions, like
      those involving the iliac arteries. In this study we sought to evaluate the
      feasibility and safety of this approach for iliac interventions. METHODS:
      Multicenter study was performed at high-volume centers with experience in
      transradial percutaneous interventions. Primary endpoint of the study was
      procedural success; secondary endpoints included in-hospital bleeding, 1-month
      freedom from adverse events and the rate of radial occlusion. Feasibility of this
      technique was evaluated by recording procedural and fluoroscopy time and contrast
      load. RESULTS: A total of 149 patients from 5 centers were enrolled. The
      population had a medium risk profile, with 48% of patients having TASC 2 or 3
      lesions. Procedural success was achieved in 98.7% of the population, and we did
      not register in-hospital complications, including both vascular access site and
      procedural-related complications. An ancillary transfemoral approach was used in
      13% of patients. One-month freedom from symptoms was achieved in 97.3% of
      patients, and the rate of radial occlusion was 2.7%. Major determinants of an
      unsuccessful procedure were the use of normal 6 or 7-Fr introducer with guiding
      catheter, TASC D lesion attempt, lesion length>30 mm and total occlusion.
      CONCLUSIONS: A transradial approach for iliac disease may be a feasible and safe
      alternative to the transfemoral route in experienced hands, in the light of
      significant technical improvements and dedicated devices.

PMID- 24861257
TI  - Easily applicable multiple testing procedures to improve the interpretation of
      clinical trials with composite endpoints.
AB  - BACKGROUND: Cardiology trials often consider composite endpoints as primary
      efficacy outcomes thereby combining several time-to-event variables in a single
      time-to-first-event measure. The main motivation to use a composite endpoint is
      to increase the number of expected events thereby reducing the required sample
      size. However, interpretation may be difficult as the effect observed for the
      composite endpoint does not necessarily reflect the effects for the single
      components. To improve interpretation, it is therefore a current standard to
      analyze the individual components in a descriptive way. However, a descriptive
      analysis does not allow a statistical proof of concept. Therefore the gain in
      information is limited. METHODS: This paper systematically explores multiple
      testing procedures aimed at improving the interpretation of composite endpoints
      by confirmatory tests of the components. A simulation study demonstrates, on the
      basis of a real cardiology clinical trial example, the benefit of these easily
      applicable multiple testing procedures. RESULTS: By applying adequate multiple
      testing strategies to assess the components of a composite endpoint there is a
      high chance to get additional confirmatory evidence on the components without the
      need to increase sample size. With a moderate increase in sample size, a gain in
      evidence can often also be ensured with a predefined power. CONCLUSION: The
      interpretation of composite endpoints can be improved by applying multiple
      testing procedures that assess the components. The methods discussed here are
      easy to apply and provide a substantial benefit for clinical interpretation of
      study results.

PMID- 24861258
TI  - 24-hour antiplatelet effect of aspirin in patients with previous definite stent
      thrombosis.
AB  - OBJECTIVE: Once-daily aspirin is standard treatment, but recent studies point
      towards increased platelet function at the end of the dosing interval. Stent
      thrombosis (ST) has been linked with reduced antiplatelet effect of aspirin, so
      we investigated if platelet inhibition by aspirin declines through 24 h in
      patients with previous definite ST. Furthermore, we explored whether increased
      levels of immature platelets and thrombopoietin are associated with a
      particularly rapid recovery of platelet function. METHODS: This case-control
      study included 50 patients with previous definite ST matched with 100 patients
      with stable coronary artery disease and 50 healthy volunteers. All participants
      were on aspirin 75 mg/day mono antiplatelet therapy. Platelet aggregation was
      measured 1 and 24 h after aspirin intake using platelet aggregometry
      (Multiplate(r) Analyzer). Cyclooxygenase-1 activity, platelet activation,
      immature platelets, and thrombopoietin were measured. RESULTS: Platelet
      aggregation increased by 109+/-150 (arachidonic acid) and 47+/-155 (collagen)
      aggregation units per minute from 1 to 24 h after aspirin intake (p-values
      <0.0001) with corresponding increases in thromboxane B2 (5.6+/-5.1 ng/ml,
      p<0.0001) and soluble P-selectin (6.2+/-15.5 ng/ml, p<0.0001). Platelet
      aggregation increased equally in all groups, but patients with previous ST
      displayed the highest levels of platelet aggregation at 24 h (p-values<=0.05) and
      the highest levels of immature platelets (p<0.01) and thrombopoietin (p<0.0001).
      CONCLUSIONS: Platelet inhibition declined significantly during the 24-hour dosing
      interval in aspirin-treated patients with previous definite ST or stable coronary
      artery disease and in healthy individuals. Increased levels of immature platelets
      and thrombopoietin were observed in patients with previous definite ST.

PMID- 24861259
TI  - Tissue concentrations of estrogens and aromatase immunolocalization in
      interstitial pneumonia of human lung.
AB  - Interstitial pneumonia (IP) is characterized by various degrees of pulmonary
      fibrosis and inflammation. Estrogens have been demonstrated to play important
      roles in physiological and pathological conditions of human lung, but
      significance of estrogens has remained unknown in human IP. Therefore, we
      measured estrogen concentrations and immunolocalized aromatase and estrogen
      receptor beta (ERbeta) in IP tissues. Estradiol concentration was significantly
      (2.8-fold) higher in IP than normal lung tissues, and aromatase activity
      evaluated by estradiol/testosterone ratio was also significantly (7.2-fold)
      elevated in IP tissues. Aromatase immunoreactivity in alveolar epithelial cells
      was significantly frequent in IP than normal lung or inflammatory lung disease
      other than IP, and it was positively associated with ERbeta immunoreactivity in
      these cells of IP. These results suggest that estradiol concentration is locally
      increased in human IP tissue by aromatase, and increased estrogens may play an
      important role in the development of IP through ERbeta in the alveolar epithelial
      cells. 

PMID- 24861260
TI  - Histone deacetylases (HDACs) in frontotemporal lobar degeneration.
AB  - AIMS: Frontotemporal lobar degeneration (FTLD) is clinically and pathologically
      heterogeneous. Although associated with variations in MAPT, GRN and C9ORF72, the
      pathogenesis of these, and of other nongenetic, forms of FTLD, remains unknown.
      Epigenetic factors such as histone regulation by histone deacetylases (HDAC) may
      play a role in the dysregulation of transcriptional activity, thought to underpin
      the neurodegenerative process. METHODS: The distribution and intensity of HDACs
      4, 5 and 6 was assessed semi-quantitatively in immunostained sections of temporal
      cortex with hippocampus, and cerebellum, from 33 pathologically confirmed cases
      of FTLD and 27 controls. RESULTS: We found a significantly greater intensity of
      cytoplasmic immunostaining for HDAC4 and HDAC6 in granule cells of the dentate
      gyrus in cases of FTLD overall compared with controls, and specifically in cases
      of FTLD tau-Picks compared with FTLD tau-MAPT and controls. No differences were
      noted between FTLD-TDP subtypes, or between the different genetic and nongenetic
      forms of FTLD. No changes were seen in HDAC5 in any FTLD or control cases.
      CONCLUSIONS: Dysregulation of HDAC4 and/or HDAC6 could play a role in the
      pathogenesis of FTLD-tau associated with Pick bodies, although their lack of
      immunostaining implies that such changes do not contribute directly to the
      formation of Pick bodies.

PMID- 24861261
TI  - Principles of differential diagnostic pacing maneuvers: serial versus parallel
      conduction.
AB  - In this article we will review differential diagnostic pacing maneuvers. It is
      not meant to be an exhaustive review of all such maneuvers. Rather, we offer some
      general analytic principles as they apply to electrophysiology (EP) and
      illustrate their use through several examples. Our hope is to provide a framework
      for thinking about electrogram data that acts more like a compass and map than
      like a specific set of directions. Amongst the most helpful pieces of advice that
      we can offer the EP trainee is to actively try to picture the waves of
      electricity spreading through the heart, passing beneath the recording electrodes
      and generating the electrograms you seek to interpret. Digest the fact that more
      than one propagation pattern can result in the same electrogram pattern and that
      differential diagnostic pacing is aimed at distinguishing between these
      possibilities. A fundamental tenet of differential diagnostic maneuvers of any
      kind (not simply pacing) is to choose a test that maximizes the difference
      between possible explanations. This perspective and a careful and meticulous
      cataloguing of what you can unambiguously conclude from the electrograms versus
      what remains to be determined via pacing offers the best approach to succeeding
      at EP. We will discuss pacing maneuvers in three contexts: differential diagnosis
      of narrow complex tachycardia, mapping of accessory pathways, and Para-Hisian
      pacing. 

PMID- 24861262
TI  - Interaction of phenazinium dyes with double-stranded poly(A): spectroscopy and
      isothermal titration calorimetry studies.
AB  - A comprehensive study on the binding of phenazinium dyes viz. janus green B,
      indoine blue, safranine O and phenosafranine with double stranded poly(A) using
      various spectroscopic and calorimetric techniques is presented. A higher binding
      of janus green B and indoine blue over safranine O and phenosafranine to poly(A)
      was observed from all experiments. Intercalative mode of binding of the dyes was
      inferred from fluorescence polarization anisotropy, iodide quenching and
      viscosity experiments. Circular dichroism study revealed significant perturbation
      of the secondary structure of poly(A) on binding of these dyes. Results from
      isothermal titration calorimetry experiments suggested that the binding was
      predominantly entropy driven with a minor contribution of enthalpy to the
      standard molar Gibbs energy. The results presented here may open new
      opportunities in the application of these dyes as RNA targeted therapeutic
      agents. 

PMID- 24861263
TI  - Multiple roles for UDP-glucuronosyltransferase (UGT)2B15 and UGT2B17 enzymes in
      androgen metabolism and prostate cancer evolution.
AB  - In the prostate, approximately 50% of androgens are from adrenal steroids, mainly
      dehydroepiandrosterone (DHEA), its sulfate and androstenedione. These compounds
      are converted first into testosterone, and then into the active hormone
      dihydrotestosterone (DHT). After having activated the androgen receptor (AR), DHT
      is reduced into androstane-3alpha-DIOL (3alpha-DIOL) and androsterone (ADT),
      which are subsequently converted into 2 inactive and easily excretable
      metabolites: 3alpha-DIOL-17glucuronide (3alpha-DIOL-17G) and ADT-3glucuronide
      (ADT-3G). The formation of these last derivatives through the glucuronidation
      reaction involves 2 UDP-glucuronosyltransferase (UGT) enzymes, namely UGT2B15 and
      UGT2B17. The present review article aims at providing a comprehensive view of the
      physiological and pharmacological importance of these 2 enzymes for the control
      of androgen homeostasis. We will resume: (i) how UGT2B15 and UGT2B17 contribute
      to androgen elimination; (ii) how their glucuronidation capacity influences the
      androgen signaling pathway in prostate cells; (iii) how they contribute to the
      anti-proliferative properties of AR antagonists in prostate cancer cells; and
      (iv) how AR and its spliced variants regulate the UGT2B15 and/or UGT2B17 genes
      expression. Finally, whether the unexploited AR-UGT axis could serve as a
      prognostic maker or a pharmacological target for novel therapeutics in the
      treatment of prostate cancer is also discussed. This article is part of a special
      issue entitled 'Essential role of DHEA'. 

PMID- 24861264
TI  - Neonatal allopregnanolone or finasteride administration modifies hippocampal K(+)
      Cl(-) co-transporter expression during early development in male rats.
AB  - The maintenance of levels of endogenous neurosteroids (NS) across early postnatal
      development of the brain, particularly to the hippocampus, is crucial for their
      maturation. Allopregnanolone (Allop) is a NS that exerts its effect mainly
      through the modulation of the GABAA receptor (GABAAR). During early development,
      GABA, acting through GABAAR, that predominantly produces depolarization shifts to
      hyperpolarization in mature neurons, around the second postnatal week in rats.
      Several factors contribute to this change including the progressive increase of
      the neuron-specific K(+)/Cl(-) co-transporter 2 (KCC2) (a chloride exporter)
      levels. Thus, we aimed to analyze whether a different profile of NS levels during
      development is critical and can alter this natural progression of KCC2 stages. We
      administrated sustained Allop (20mg/kg) or Finasteride (5alpha-reductase
      inhibitor, 50mg/kg) from the 5th postnatal day (PD5) to PD9 and assessed changes
      in the hippocampal expression of KCC2 at transcript and protein levels as well as
      its active phosphorylated state in male rats. Taken together data indicated that
      manipulation of NS levels during early development influence KCC2 levels and
      point out the importance of neonatal NS levels for the hippocampal development. 

PMID- 24861265
TI  - A comparative study of the androgenic properties of progesterone and the
      progestins, medroxyprogesterone acetate (MPA) and norethisterone acetate (NET-A).
AB  - The importance of investigating the molecular mechanism of action of
      medroxyprogesterone acetate (MPA) and norethisterone acetate (NET-A), two
      clinically important progestins used in hormone therapy (HT), has been
      highlighted by clinical evidence showing that MPA and norethisterone (NET)
      increase the risk of the development of breast cancer in HRT users, and that MPA
      may increase susceptibility to- and transmission of HIV-1. The aim of this study
      was to compare the molecular mechanisms of action of MPA, NET-A and progesterone
      (Prog) via the androgen receptor (AR) in a cell line model that can minimize
      confounding factors such as the presence of other steroid receptors. This study
      is the first to determine accurate apparent Ki values for Prog, MPA and NET-A
      toward the human AR in COS-1 cells. The results reveal that these ligands have a
      similar binding affinity for the AR to that of the natural androgen 5alpha
      dihydrotestosterone (DHT) (Ki's for DHT, Prog, MPA and NET-A are 29.4, 36.6, 19.4
      and 21.9 nM, respectively). Moreover, in both transactivation and transrepression
      transcriptional assays we demonstrate that, unlike Prog, MPA and NET-A are
      efficacious AR agonists, with activities comparable to DHT. One of the most novel
      findings of our study is that NET-A, like DHT, induces the ligand-dependent
      interaction between the NH2- and COOH-terminal domains (N/C-interaction) of the
      AR independent of promoter-context, while MPA does not induce the N/C interaction
      on a classical ARE and does so only weakly on an AR-selective ARE. This suggests
      that MPA and NET-A may exert differential promoter-specific actions via the AR in
      vivo. Consistent with this, molecular modeling suggests that MPA and NET-A induce
      subtle differences in the structure of the AR ligand binding domain. Taken
      together, the results from this study suggest that unlike Prog, both MPA and NET
      A used in hormonal therapy are likely to compete with DHT and exert significant
      and promoter-specific off-target transcriptional effects via the AR, possibly
      contributing to some of the observed side-effects with the clinical use of MPA
      and NET-A.

PMID- 24861266
TI  - The balance of cortisol-cortisone interconversion is shifted towards cortisol in
      neonates with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.
AB  - BACKGROUND: Patients with congenital adrenal hyperplasia due to 21-hydroxylase
      deficiency (21OHD) have an impaired cortisol synthesis, but it is unknown whether
      the metabolism of glucocorticoids differs between neonates and infants with and
      without 21OHD. OBJECTIVE: The objective of this study was to compare the
      glucocorticoid metabolism between neonates and infants with and without 21OHD.
      METHODS: We analyzed 14 urinary glucocorticoid metabolites, 7 metabolites each of
      cortisol and cortisone, by gas chromatography-mass spectrometry of 89 untreated
      21OHD neonates and infants and 161 neonates and infants without 21OHD. RESULTS:
      Neonates with 21OHD exhibit elevated relative amounts of cortisol metabolites in
      total glucocorticoid metabolism and an increased ratio of cortisol to cortisone
      metabolites (p<0.0001). This reflects a shift toward cortisol in the relative
      balance of the interconversion between cortisol and cortisone. The ratio of
      cortisol to cortisone metabolites correlated significantly with low urinary
      glucocorticoid concentrations (p<0.03), with low 21-hydroxylase activity
      (p<0.001) and high urinary sodium and chloride concentrations (p<0.05) in
      neonates with 21OHD. CONCLUSIONS: Our results demonstrate substantial changes in
      the relative cortisone to cortisol interconversion in neonates with 21OHD. The
      shift of glucocorticoid metabolism toward active cortisol in neonates with 21OHD
      seems to be related to the severity of 21OHD and adrenal dysfunction. Our data
      provide new insights into the regulation of glucocorticoid homeostasis in 21OHD.

PMID- 24861267
TI  - Low-intensity resistance training attenuates dexamethasone-induced atrophy in the
      flexor hallucis longus muscle.
AB  - This study investigated the potential protective effect of low-intensity
      resistance training (RT) against dexamethasone (DEX) treatment induced muscle
      atrophy. Rats underwent either an 8 week period of ladder climbing RT or remained
      sedentary. During the last 10 days of the exercise protocol, animals were
      submitted to a DEX treatment or a control saline injection. Muscle weights were
      assessed and levels of AKT, mTOR, FOXO3a, Atrogin-1 and MuRF-1 proteins were
      analyzed in flexor hallucis longus (FHL), tibialis anterior (TA), and soleus
      muscles. DEX induced blood glucose increase (+46%), body weight reduction (-19%)
      and atrophy in FHL (-28%) and TA (-21%) muscles, which was associated with a
      decrease in AKT and an increase in MuRF-1 proteins levels. Low-intensity RT
      prevented the blood glucose increase, attenuated the FHL atrophy effects of DEX,
      and was associated with increased mTOR and reductions in Atrogin-1 and MuRF-1 in
      FHL. In contrast, TA muscle atrophy and signaling proteins were not affected by
      RT. These are the first data to demonstrate that low-intensity ladder-climbing RT
      specifically mitigates the FHL atrophy, which is the main muscle recruited during
      the training activity, while not preventing atrophy in other limb muscle not as
      heavily recruited. The recruitment-dependent prevention of atrophy by low
      intensity RT likely occurs by a combination of attenuated muscle protein
      degradation signals and enhanced muscle protein synthesis signals including mTOR,
      Atrogin-1 and MuRF-1. 

PMID- 24861268
TI  - Global emission inventories for C4-C14 perfluoroalkyl carboxylic acid (PFCA)
      homologues from 1951 to 2030, part II: the remaining pieces of the puzzle.
AB  - We identify eleven emission sources of perfluoroalkyl carboxylic acids (PFCAs)
      that have not been discussed in the past. These sources can be divided into three
      groups: [i] PFCAs released as ingredients or impurities, e.g., historical and
      current use of perfluorobutanoic acid (PFBA), perfluorohexanoic acid (PFHxA) and
      their derivatives; [ii] PFCAs formed as degradation products, e.g., atmospheric
      degradation of some hydrofluorocarbons (HFCs) and hydrofluoroethers (HFEs); and
      [iii] sources from which PFCAs are released as both impurities and degradation
      products, e.g., historical and current use of perfluorobutane sulfonyl fluoride
      (PBSF)- and perfluorohexane sulfonyl fluoride (PHxSF)-based products. Available
      information confirms that these sources were active in the past or are still
      active today, but due to a lack of information, it is not yet possible to
      quantify emissions from these sources. However, our review of the available
      information on these sources shows that some of the sources may have been
      significant in the past (e.g., the historical use of PFBA-, PFHxA-, PBSF- and
      PHxSF-based products), whereas others can be significant in the long-term (e.g.,
      (bio)degradation of various side-chain fluorinated polymers where PFCA precursors
      are chemically bound to the backbone). In addition, we summarize critical
      knowledge and data gaps regarding these sources as a basis for future research. 

PMID- 24861269
TI  - Treatment of paediatric cholestasis due to canalicular transport defects: yet
      another step forward.

PMID- 24861270
TI  - Ribavirin with interferon for hepatitis C in dialysis patients: efficacious and
      safe in the right patients in good hands.

PMID- 24861271
TI  - A design strategy for the hierarchical fabrication of colloidal hybrid
      mesostructures.
AB  - Advances in nanotechnology depend upon expanding the ability to create new and
      complex materials with well-defined multidimensional mesoscale structures. The
      creation of hybrid hierarchical structures by combining colloidal organic and
      inorganic building blocks remains a challenge due to the difficulty in preparing
      organic structural units of precise size and shape. Here we describe a design
      strategy to generate controlled hierarchical organic-inorganic hybrid
      architectures by multistep bottom-up self-assembly. Starting with a suspension of
      large inorganic nanoparticles, we anchor uniform block copolymer crystallites
      onto the nanoparticle surface. These colloidally stable multi-component particles
      can initiate the living growth of uniform cylindrical micelles from their
      surface, leading to three-dimensional architectures. Structures of greater
      complexity can be obtained by extending the micelles via addition of a second
      core-crystalline block copolymer. This controlled growth of polymer micelles from
      the surface of inorganic particles opens the door to the construction of
      previously inaccessible colloidal organic-inorganic hybrid structures. 

PMID- 24861272
TI  - Routine developmental, autism, behavioral, and psychological screening in
      epilepsy care settings.
AB  - AIM: Screening for cognitive impairment, developmental delay, and
      neuropsychiatric problems is not always performed in children with epilepsy. The
      aim of this study was to assess the value of this screening and its validity for
      determining previously unidentified ('actionable') problems in children with
      epilepsy. METHOD: New and existing patients with epilepsy were recruited from a
      hospital-based epilepsy center. The parent of the child completed screening
      evaluations for development (Ages and Stages Questionnaire [ASQ], 0-66mo), autism
      (Modified Checklist for Autism in Toddlers [mCHAT], 16-30mo), social
      communication (Social Communication Questionnaire [SCQ], >=4y), and psychiatric
      concerns (Strengths and Difficulties Questionnaire [SDQ], 4-17y). RESULTS: We
      screened 236 children overall (136 males [58%], 100 females [42%]; mean age [SD]
      6y 7mo [4y 6mo]). Of these, 176 children (75%) had established epilepsy diagnoses
      and 60 (25%) were patients with new-onset epilepsy. Of those with new-onset
      disease, 22 (37%) were determined not to have epilepsy. Positive findings by test
      were 82% (ASQ), 54% (mCHAT), 15%, (SCQ), and 58% (SDQ). Findings were actionable
      in 46 children (20%): 18% of findings in children with established epilepsy and
      23% of findings in patients with new-onset epilepsy. Of the 46 children for whom
      further referrals were made, the parents of 28 (61%) have pursued further
      evaluations. INTERPRETATION: In this study, children with existing and new-onset
      diagnoses of epilepsy had actionable screening findings. These findings support
      the development of systematic screening of comorbidities for children with
      epilepsy.

PMID- 24861274
TI  - p-type conductivity generated by ferromagnetic ordering via percolative anionic H
      chain formation in ZnCoO.
AB  - We report on the simultaneous realization of p-type conductivity and strong
      ferromagnetism in heavily Co-doped ZnO thin films in the presence of a high
      concentration of hydrogen impurities. Through ab initio calculations, we find
      that the microscopic origin of hole carrier generations and ferromagnetic
      ordering is due to the partially occupied band of the percolative structures
      wherein the carrier-induced magnetic interactions can stabilize the strong spin
      parallel state. 

PMID- 24861273
TI  - A detailed three-step protocol for live imaging of intracellular traffic in
      polarized primary porcine RPE monolayers.

PMID- 24861275
TI  - Heme oxygenase-1 in diabetic vascular dysfunction.

PMID- 24861277
TI  - Conversation therapy for aphasia: a qualitative review of the literature.
AB  - BACKGROUND: A diverse literature addresses elements of conversation therapy in
      aphasia including intervention rooted in conversation analysis, partner training,
      group therapy and behavioural intervention. Currently there is no resource for
      clinicians or researchers that defines and organizes this information into a
      coherent synopsis describing various conversation therapy practices. AIMS: To
      organize information from varied sources into a descriptive overview of
      conversation therapy for aphasia. METHODS & PROCEDURES: Academic search engines
      were employed to identify research articles published between 1950 and September
      2013 reporting on conversation therapy for aphasia. Thirty articles met criteria
      for review and were identified as primary sources for the qualitative review.
      Using qualitative methodology, relevant data were extracted from articles and
      categories were identified to create a descriptive taxonomy of conversation
      therapy for aphasia. MAIN CONTRIBUTION: Conversation interventions were divided
      into descriptive categories including: treatment participants (person with
      aphasia, partner, dyad), primary guiding orientation (conversation analysis,
      social model, behavioural, relationship centred), service delivery (individual,
      group), focus of intervention (generic/individualized; problem/solution oriented;
      compensatory), training methods (explicit/implicit; external/embedded),
      activities or tasks, and outcomes measured. Finally, articles were categorized by
      research design. There was marked variation in conversation therapy approaches
      and outcome measures reported and a notable gap in information about one-on-one
      conversation therapy for individuals with aphasia. CONCLUSIONS & IMPLICATIONS:
      This review provides a description of various conversation therapy approaches and
      identified gaps in the existing literature. Valid measures of natural
      conversation, research on one-on-one conversation approaches for individuals with
      aphasia, and a systematic body of evidence consisting of high quality research
      are needed.

PMID- 24861276
TI  - Pharmacokinetic evaluation of different generic triclabendazole formulations in
      heifers.
AB  - AIMS: To assess the comparative drug systemic exposure of a reference (RF) and
      four test (Test I, Test II, Test III and Test IV) formulations of triclabendazole
      (TCBZ) in heifers. METHODS: Thirty Holstein heifers were randomly distributed
      into five groups (n=6 per group). Animals in the RF group received the reference
      formulation (Fasinex), and those in the other groups received different
      commercially available TCBZ formulations (Test I, Test II, Test III and Test IV).
      All treatments were orally administered at 12 mg/kg bodyweight. The
      concentrations of TCBZ metabolites in plasma between 0 and 168 hours after
      treatment were quantified by high-performance liquid chromatography (HPLC).
      RESULTS: Triclabendazole sulphoxide (TCBZ.SO) and TCBZ-sulphone (TCBZ.SO2) were
      the only analytes recovered in plasma. Only the Test I formulation did not differ
      from the RF for all pharmacokinetic parameters measured for either metabolite
      (p>0.8). The TCBZ.SO area under the concentration vs. time curve for Test II
      formulation (268.9 ug.h/mL) was lower, and for Test III (619.9 ug.h/mL) and Test
      IV (683.4 ug.h/mL) was higher, than the RF (418.1 ug.h/mL) (p<0.005). CONCLUSION:
      Based on the currently available bioequivalence criteria, the only test
      formulation under evaluation that could be considered equivalent to the RF was
      the Test I formulation, which demonstrated an equivalent systemic exposure for
      the active TCBZ.SO metabolite. This comparison of TCBZ pioneer and test
      formulations in cattle raises awareness of the need for further quality control
      for drug approval in the veterinary pharmaceutical field in many regions of the
      world.

PMID- 24861278
TI  - Haematological abnormalities in systemic lupus erythematosus.
AB  - OBJECTIVES: This study was conducted to evaluate the frequency and pattern of
      haematological abnormalities (HA) in SLE patients at the time of diagnosis and
      last follow-up, and their relationship with organ involvement. PATIENTS AND
      METHODS: This retrospective study included patients who were diagnosed and
      treated for SLE from 1982 to 2008 at King Khalid University hospital, Riyadh.
      Demographic and haematological parameters at diagnosis and the last follow-up,
      disease manifestations, organ involvement and clinical hematological
      complications were recorded. Association of HA with organ involvement was
      explored by multivariate analysis. RESULTS: A total of 624 patients (90.7%
      females, mean age 34.3+/-11.9 years) were studied. HA were present in 516 (82.7
      %) patients at the time of diagnosis. Anemia was the most frequent HA in 63.0%
      patients followed by lymphopenia in 40.3%, leukopenia in 30.0%, thrombocytopenia
      in 10.9% and autoimmune hemolytic anemia (AIHA) in 4.6% patients. Deep vein
      thrombosis and pulmonary embolism were diagnosed in 7.4% and 2.6% patients
      respectively. After a mean follow-up of 9.3+/-5.3 years, 329/491 (67%) patients
      still had some HA present. Anemia remained the most common abnormality (51.7%
      patients) followed by lymphopenia in 33.1%, and thrombocytopenia in 4.8%
      patients. Leucopenia was associated with oral ulcers (p=0.021) and alopecia
      (p=0.031), anemia with renal disease (p=0.017), AIHA with neurological
      involvement (p=0.003), elevated IgG with malar rash (p=0.027), and low C3 with
      serositis (p=0.026). CONCLUSION: HA are very common at the time of diagnosis and
      during follow-up in SLE, and some of these abnormalities are associated with
      organ damage. This information may help in better management planning of SLE
      patients.

PMID- 24861279
TI  - The gap in patient protection for outpatient cosmetic surgery.

PMID- 24861280
TI  - On the plasmonic photovoltaic.
AB  - The conversion of sunlight into electricity by photovoltaics is currently a
      mature science and the foundation of a lucrative industry. In conventional
      excitonic solar cells, electron-hole pairs are generated by light absorption in a
      semiconductor and separated by the "built in" potential resulting from charge
      transfer accompanying Fermi-level equalization either at a p-n or a Schottky
      junction, followed by carrier collection at appropriate electrodes. Here we
      report a stable, wholly plasmonic photovoltaic device in which photon absorption
      and carrier generation take place exclusively in the plasmonic metal. The field
      established at a metal-semiconductor Schottky junction separates charges. The
      negative carriers are high-energy (hot) electrons produced immediately following
      the plasmon's dephasing. Some of the carriers are energetic enough to clear the
      Schottky barrier or quantum mechanically tunnel through it, thereby producing the
      output photocurrent. Short circuit photocurrent densities in the range 70-120 MUA
      cm(-2) were obtained for simulated one-sun AM1.5 illumination with devices based
      on arrays of parallel gold nanorods, conformally coated with 10 nm TiO2 films and
      fashioned with a Ti metal collector. For the device with short circuit currents
      of 120 MUA cm(-2), the internal quantum efficiency is ~2.75%, and its wavelength
      response tracks the absorption spectrum of the transverse plasmon of the gold
      nanorods indicating that the absorbed photon-to-electron conversion process
      resulted exclusively in the Au, with the TiO2 playing a negligible role in charge
      carrier production. Devices fabricated with 50 nm TiO2 layers had open-circuit
      voltages as high as 210 mV, short circuit current densities of 26 MUA cm(-2), and
      a fill factor of 0.3. For these devices, the TiO2 contributed a very small but
      measurable fraction of the charge carriers. 

PMID- 24861281
TI  - BTEX air concentrations and self-reported common health problems in gasoline
      sellers from Cotonou, Benin.
AB  - To examine the relation between BTEX exposure levels and common self-reported
      health problems in 140 gasoline sellers in Cotonou, Benin, a questionnaire
      documenting their socioeconomic status and their health problems was used,
      whereas 18 of them went through semi-directed qualitative individual interviews
      and 17 had air samples taken on their workplace for BTEX analysis. Median
      concentrations for BTEX were significantly lower on official (range of medians:
      54-207 MUg/m3, n = 9) vs unofficial (148-1449 MUg/m3, n = 8) gasoline-selling
      sites (p < 0.05). Self-reported health problems were less frequently reported in
      sellers from unofficial vs official selling sites (p < 0.05), because, as
      suggested by the semi-directed interviews, of their fear of losing their
      important, but illegal, source of income. Concluding, this study has combined
      quantitative and qualitative methodological approaches to account for the complex
      socioeconomic and environmental conditions of the investigated sellers, leading
      to their, in some cases, preoccupying BTEX exposure.

PMID- 24861283
TI  - Scientific progress versus ecological influence on Schistosoma mansoni
      transmission.

PMID- 24861282
TI  - A new X-ray fluorescence spectroscopy for extraterrestrial materials using a muon
      beam.
AB  - The recent development of the intense pulsed muon source at J-PARC MUSE, Japan
      Proton Accelerator Research Complex/MUon Science Establishment (10(6) s(-1) for a
      momentum of 60 MeV/c), enabled us to pioneer a new frontier in analytical
      sciences. Here, we report a non-destructive elemental analysis using u(-)
      capture. Controlling muon momentum from 32.5 to 57.5 MeV/c, we successfully
      demonstrate a depth-profile analysis of light elements (B, C, N, and O) from
      several mm-thick layered materials and non-destructive bulk analyses of
      meteorites containing organic materials. Muon beam analysis, enabling a bulk
      analysis of light to heavy elements without severe radioactivation, is a unique
      analytical method complementary to other non-destructive analyses. Furthermore,
      this technology can be used as a powerful tool to identify the content and
      distribution of organic components in future asteroidal return samples.

PMID- 24861284
TI  - Revisiting the concept of hepatosplenic schistosomiasis and its challenges using
      traditional and new tools.
AB  - Different aspects of hepatosplenic schistosomiasis are revisited here. Manson's
      schistosomiasis causes periportal fibrosis and portal hypertension in
      approximately 6% of infected subjects, usually with preservation of their hepatic
      function. The assessment of liver involvement is of major importance in
      determining the prognosis and risk of complications from schistosomiasis, such as
      upper digestive bleeding secondary to variceal rupture. For many years, the
      diagnosis of hepatosplenic schistosomiasis and liver fibrosis was made by
      abdominal palpation and the finding of liver and/or spleen enlargement. However,
      there is no consensus regarding the clinical parameters of the liver and spleen
      to be considered in this physical evaluation. For the last three decades,
      abdominal ultrasound (US) has become the best imaging technique to evaluate liver
      fibrosis caused by schistosomiasis mansoni. However, US is a subjective procedure
      and is therefore examiner-dependent. Magnetic resonance imaging (MRI) findings
      have provided valuable information in addition to ultrasound and clinical
      examination. The combination of a comprehensive history and physical examination,
      basic laboratory tests (a stool examination for Schistosoma mansoni eggs and a
      blood cell count), biomarkers for liver fibrosis/portal hypertension and imaging
      methods seem to offer the best approach for evaluating patients with this
      disease. In situations where research is involved or in patients with severe
      disease, MRI may be considered. 

PMID- 24861285
TI  - Impact of the IL-18 gene polymorphism in response to antiviral therapy in chronic
      HCV genotype 4 patients.
AB  - INTRODUCTION: Interleukin (IL)-18 is a well-known major proinflammatory cytokine
      with broad biological effects. The major immunomodulatory functions of IL-18
      include enhancing T cell and natural killer cell cytotoxicity. Serum levels of
      this cytokine were shown to increase in chronic hepatitis C patients compared to
      non-infected healthy people. An association between IL-18 gene promoter
      polymorphisms and pegylated interferon (PEG-IFN) and ribavirin treatment outcomes
      has been reported for individuals with chronic hepatitis C virus genotype 1 (HCV
      1). In this study, HCV genotype 4 (HCV-4) patients were assessed for IL-18 gene
      polymorphisms and treatment outcomes or severity of liver disease because data
      concerning the impact of IL-18 gene polymorphisms on patients with HCV-4
      infections are limited. METHODS: This study included 123 chronic HCV-4 Egyptian
      patients and 123 apparently healthy volunteer blood donors who served as a
      control group. HCV genotyping was performed using the line probe assay. IL-18
      genotyping was performed using the TaqMan Real-Time PCR method in all 246 patient
      and control samples. RESULTS: In our study, all patients had HCV-4. IL-18 gene
      single nucleotide polymorphism (SNP) (-607C/A) genotype distributions and allele
      frequencies did not differ between HCV patients and normal healthy subjects or
      between patient groups when compared according to the therapeutic response.
      Moreover, the presence of an IL-18 SNP was not associated with histological
      disease severity. We conclude that the presence of the IL-18 SNP rs1946518 does
      not affect the outcome of chronic HCV-4 treatment in Egyptian patients.
      CONCLUSIONS: The IL-18 SNP rs1946518 does not affect response to treatment in
      chronic HCV-4 patients.

PMID- 24861287
TI  - Depressive symptoms and harmful alcohol use in hepatitis C patients: prevalence
      and correlates.
AB  - INTRODUCTION: It is important to understand the characteristics and
      vulnerabilities of people who have hepatitis C because this disease is currently
      an important public health problem. The objective of this study was to estimate
      the prevalence of depressive symptoms and harmful alcohol use in patients with
      hepatitis C and to study the association between these outcomes and demographic,
      psychosocial and clinical variables. METHODS: This cross-sectional, descriptive
      and analytical study involved 82 hepatitis C patients who were being treated with
      pegylated interferon and ribavirin at a public university hospital. The primary
      assessments used in the study were the Alcohol Use Disorders Identification Test
      and the Beck Depression Inventory. Bivariate analyses were followed by logistic
      regression. RESULTS: The prevalence of depressive symptoms was 30.5% (n=25), and
      that of harmful alcohol use was 34.2% (n=28). Logistic regression analysis showed
      that individuals who were dissatisfied with their social support (OR=4.41;
      CI=1.00-19.33) and were unemployed (OR=6.31; CI=1.44-27.70) were at a higher risk
      for depressive symptoms, whereas harmful alcohol use was associated with the male
      sex (OR=6.78; CI=1.38-33.19) and the use of illicit substances (OR=7.42; CI=1.12
      49.00). CONCLUSIONS: High prevalence rates of depressive symptoms and harmful
      alcohol use were verified, indicating vulnerabilities that must be properly
      monitored and treated to reduce emotional suffering in this population.

PMID- 24861286
TI  - Do differences exist between chronic hepatitis C genotypes 2 and 3?
AB  - INTRODUCTION: Six genotypes of the hepatitis C virus (HCV) have been identified
      thus far, and their distribution is well defined. Genotype 1, which is the most
      prevalent worldwide, is always compared to genotypes 2 and 3, particularly in
      terms of treatment response. However, little is known about the differences
      between genotypes 2 and 3 because these genotypes are analyzed together in most
      studies. Therefore, the aim of this study was to evaluate differences in the
      clinical, epidemiological, laboratory, and histological parameters between HCV-2
      and HCV-3. METHODS: Patients with chronic hepatitis C infected with genotypes 2
      and 3 were studied retrospectively and compared according to clinical,
      laboratory, and histological aspects. Hepatitis C virus-ribonucleic acid (HCV
      RNA) was analyzed quantitatively by TaqMan(r) real-time PCR, and the HCV genotype
      was determined by sequencing the 5'-untranslated region. RESULTS: A total of 306
      patients with chronic HCV-2 (n=50) and HCV-3 (n = 256) were studied. Subtype 2b
      (n=17/50) and subtype 3a (n=244/256) were the most prevalent among patients
      infected with HCV-2 and HCV-3, respectively. The mean age was 47 +/- 10 years,
      and there was a predominance of men in the group studied (61%). Comparative
      analysis between HCV-2 and HCV-3 showed a younger age (p=0.002), less prevalence
      of arterial hypertension (p=0.03), higher serum albumin levels (p=0.01), more
      advanced stage of liver fibrosis (p=0.03), and higher frequency of steatosis in
      patients with HCV-3 (p=0.001). After multivariate regression analysis, all the
      variables, except serum albumin, remained as variables associated with HCV-3 in
      the final model. CONCLUSIONS: Clinical and histological differences exist between
      HCV-2 and HVC-3, which suggests the need for separate analyses of these
      genotypes.

PMID- 24861288
TI  - Clinical and laboratory characteristics associated with dyslipidemia and liver
      steatosis in chronic HBV carriers.
AB  - INTRODUCTION: Chronic hepatitis B virus (HBV) infection and liver steatosis (LS)
      are the most common causes of chronic liver disease, and their coexistence is
      frequently observed in clinical practice. Although metabolic syndrome is the main
      cause of LS, it has not been associated with HBV infection. The aims of this
      study were to describe the lipid profile and prevalence of LS among HBV carriers
      and to identify the characteristics associated with LS in this group. METHODS:
      This retrospective cross-sectional study included hepatitis B surface antigen
      (HBsAg)-positive patients evaluated during 2011 and 2012. RESULTS: Of the 83
      patients included, the mean age was 46.4+/-12.5 years, 53% were men, and 9.1%
      were hepatitis B e antigen (HBeAg) -positive. These patients exhibited the
      following lipid profile: total cholesterol = 175.4+/-38.8mg/dL, low-density
      lipoprotein (LDL) = 113.0+/-32.7mg/dL, and triglycerides = 91.1+/-45.2mg/dL.
      Their fasting glucose was 95.3+/-14.5g/dL, and fasting insulin was 6.1+/
      5.9uIU/mL. Liver steatosis was observed on abdominal ultrasound in 11.3% of
      individuals. Factors associated with the presence of LS included higher levels of
      total cholesterol, prothrombin activity, fasting insulin, and body mass index
      (BMI) as well as lower levels of aspartate aminotransferase (AST). CONCLUSIONS:
      These findings suggest that LS in patients with chronic HBV appears to be a
      consequence of metabolic alterations and insulin action rather than of viral
      factors.

PMID- 24861289
TI  - Investigation of class 1 integrons in Klebsiella pneumoniae clinical and
      microbiota isolates belonging to different phylogenetic groups in Recife, State
      of Pernambuco.
AB  - INTRODUCTION: The high prevalence of Klebsiella pneumoniae infections is related
      to the ability of K. pneumoniae to acquire and disseminate exogenous genes
      associated with mobile elements, such as R plasmids, transposons and integrons.
      This study investigated the presence of class 1 integrons in clinical and
      microbiota isolates of K. pneumoniae belonging to different phylogenetic groups
      and correlated these results with the antimicrobial resistance profiles of the
      studied isolates. METHODS: Of the 51 isolates of K. pneumoniae selected for this
      study, 29 were from multidrug-resistant clinical isolates, and 22 were from
      children's microbiota. The susceptibility profile was determined using the disk
      diffusion method, and class 1 integrons were detected through polymerase chain
      reaction (PCR). RESULTS: The results showed that none of the 22 microbiota
      isolates carried class 1 integrons. Among the 29 clinical isolates, 19 (65.5%)
      contained class 1 integrons, and resistance to sulfamethoxazole/trimethoprim was
      identified in 18 of these isolates (94.7%). Among the K. pneumoniae isolates with
      class 1 integrons, 47% belonged to the KpI phylogenetic group, and one isolate
      (14.3%) carrying these genetic elements belonged to the KpIII group. CONCLUSIONS:
      The wide variety of detected class 1 integrons supports the presence of high
      rates of antimicrobial resistance, genetic variability, and rapid dissemination
      of beta-lactamase genes among K. pneumoniae clinical isolates in recent years in
      hospitals in Recife-PE, Brazil. The findings of this study indicate that the
      surveillance of K. pneumoniae integrons in clinical isolates could be useful for
      monitoring the spread of antibiotic resistance genes in the hospital environment.

PMID- 24861290
TI  - Incidence of congenital syphilis in the South Region of Brazil.
AB  - INTRODUCTION: The aim of this study was to establish the incidence rates of
      congenital syphilis in the South Region of Brazil from 2001 to 2009. METHODS:
      Temporal ecological and descriptive study based on the cases recorded by the
      System of Information of Notifiable Diseases. RESULTS: The incidence of
      congenital syphilis has been increasing in the South Region of Brazil since 2004;
      the highest incidence rates were in women who received prenatal care (113.5 new
      cases per 100,000 births, p<0.001), who were diagnosed with syphilis at pregnancy
      (69.8 new cases per 100,000 births, p=0.001), and whose partner did not undergo
      treatment for syphilis (53.1 new cases per 100,000 births, p=0.001). CONCLUSIONS:
      The population of the present study mostly consisted of adult black women with
      low educational levels who attended prenatal care, who were diagnosed with
      syphilis during pregnancy, and whose partners were not treated for syphilis.
      Based on these results, actions are recommended to reduce the incidence of this
      disease, which is preventable by early diagnosis and appropriate treatment. The
      present was merely an ecological study; therefore, further investigations are
      necessary to elucidate the causes of these findings.

PMID- 24861291
TI  - Syphilis seroprevalence estimates of Santa Catarina blood donors in 2010.
AB  - INTRODUCTION: Knowledge of blood donor characteristics is essential to better
      guide clinical and serological screening for hemotherapy. The objective of this
      study was to determine the syphilis seroprevalence and the associated factors of
      blood donors in the State of Santa Catarina, Brazil. METHODS: This population
      based study from the State of Santa Catarina used information obtained from blood
      donation records. We analyzed 83,396 blood donor records generated from donors
      who were considered eligible to donate between January and August 2010. The aim
      of the study was to estimate the syphilis seroprevalence and its relationship
      with educational level, age, gender, geographical region and having donated blood
      in the past 12 months. We used descriptive analyses and a Poisson regression to
      calculate the prevalence ratios for the variables of interest. RESULTS: We found
      a 0.14% overall seroprevalence and significant differences among the following:
      first-time blood donors (0.19%) versus repeat donors (0.03% to 0.08%); low
      educational levels (0.30%) versus medium and high educational levels (0.08% to
      0.19%); and donors who did not report their residence (0.88%) or age (6.94%)
      versus those who did. Increased syphilis seroprevalence was also significantly
      associated with increased age. CONCLUSION: High syphilis seroprevalence was
      associated with lower educational level, age, first-time donation and the failure
      to provide age or residence information.

PMID- 24861292
TI  - Evaluation of the Chagas disease control program in Acucena Municipality, Rio
      Doce Valley, State of Minas Gerais, Brazil.
AB  - INTRODUCTION: Acucena Municipality, Rio Doce Valley, State of Minas Gerais,
      Brazil temporarily (2001-2005) interrupted epidemiological surveillance for
      Chagas disease. The objective of this work was to evaluate the Chagas Disease
      Control Program (CDCP) in Acucena and to offer suggestions for improving local
      epidemiological surveillance. METHODS: This study was conducted in three phases:
      I) a serological investigation of schoolchildren aged 5 to 15 years using an
      enzyme-linked immunosorbent assay (ELISA) test performed on blood collected on
      filter paper followed by ELISA, indirect immunofluorescence (IIF) and indirect
      hemaglutination (IHA) on venous blood for borderline cases and those in the gray
      zone of reactivity; II) vector evaluation using the data obtained by local health
      agents during 2006-2010; and III) examination by ELISA, IIF and IHA of serum
      samples from the inhabitants of houses where infected Triatoma vitticeps was
      found and evaluation of their knowledge about Chagas disease. RESULTS: Five
      individuals had inconclusive results in the ELISA screening but were seronegative
      for Chagas disease. The triatomine evaluation revealed the presence of three
      species: Triatoma vitticeps, Panstrongylus megistus and Panstrongylus diasi.
      Triatoma vitticeps was the most prevalent and widespread, with a higher (67%)
      index of Trypanosoma cruzi flagellates and evidence of colonization. Most of the
      inhabitants of the infested houses recognized triatomines and had basic knowledge
      about Chagas disease. CONCLUSIONS: Although T. vitticeps is not clearly
      associated with Chagas disease transmission, these results highlight the
      importance of maintaining CDCP in endemic areas and the need for greater emphasis
      on epidemiological surveillance, especially in areas with important vectorial
      changes or that have been modified by human intervention.

PMID- 24861293
TI  - A comparison of four DNA extraction protocols for the analysis of urine from
      patients with visceral leishmaniasis.
AB  - INTRODUCTION: Polymerase chain reaction (PCR) may offer an alternative diagnostic
      option when clinical signs and symptoms suggest visceral leishmaniasis (VL) but
      microscopic scanning and serological tests provide negative results. PCR using
      urine is sensitive enough to diagnose human visceral leishmaniasis (VL). However,
      DNA quality is a crucial factor for successful amplification. METHODS: A
      comparative performance evaluation of DNA extraction methods from the urine of
      patients with VL using two commercially available extraction kits and two phenol
      chloroform protocols was conducted to determine which method produces the highest
      quality DNA suitable for PCR amplification, as well as the most sensitive, fast
      and inexpensive method. All commercially available kits were able to shorten the
      duration of DNA extraction. RESULTS: With regard to detection limits, both
      phenol: chloroform extraction and the QIAamp DNA Mini Kit provided good results
      (0.1 pg of DNA) for the extraction of DNA from a parasite smaller than Leishmania
      (Leishmania) infantum (< 100fg of DNA). However, among 11 urine samples from
      subjects with VL, better performance was achieved with the phenol:chloroform
      method (8/11) relative to the QIAamp DNA Mini Kit (4/11), with a greater number
      of positive samples detected at a lower cost using PCR. CONCLUSION: Our results
      demonstrate that phenol:chloroform with an ethanol precipitation prior to
      extraction is the most efficient method in terms of yield and cost, using urine
      as a non-invasive source of DNA and providing an alternative diagnostic method at
      a low cost.

PMID- 24861294
TI  - Toxoplasmosis: an examination of knowledge among health professionals and
      pregnant women in a municipality of the State of Parana.
AB  - INTRODUCTION: The aim of this study was to investigate the knowledge of
      toxoplasmosis among professionals and pregnant women in the public health
      services in Parana, Brazil. METHODS: A cross-sectional observational and
      transversal study of 80 health professionals (44 nurses and 36 physicians) and
      330 pregnant women [111 immunoglobulin M (IgM)- and IgG-non-reactive and 219 IgG
      reactive] was conducted in 2010. An epidemiological data questionnaire was
      administered to the professionals and to the pregnant women, and a questionnaire
      about the clinical aspects and laboratory diagnosis of toxoplasmosis was
      administered to the professionals. RESULTS: The participants frequently provided
      correct responses about prophylactic measures. Regarding the clinical and
      laboratory aspects, the physicians provided more correct responses and discussed
      toxoplasmosis with the pregnant women. The professionals had difficulty
      interpreting the avidity test results, and the physicians stated that they
      referred pregnant women with high-risk pregnancies to a county reference center.
      Of the professionals, 53 (91.4%) reported that they instructed women during
      prenatal care, but only 54 (48.6%) at-risk pregnant women and 99 (45.2%) women
      who were not at risk reported receiving information about preventive measures.
      The physicians provided verbal instructions to 120 (78.4%) women, although
      instructional materials were available in the county. The pregnant women
      generally lacked knowledge about preventive measures for congenital
      toxoplasmosis, but the at-risk pregnant women tended to respond correctly.
      CONCLUSIONS: This study provides data to direct public health policies regarding
      the importance of updating the knowledge of primary care professionals.
      Mechanisms should be developed to increase public knowledge because prophylactic
      strategies are important for preventing congenital toxoplasmosis.

PMID- 24861295
TI  - Prevalence of latent tuberculosis and treatment adherence among patients with
      chronic kidney disease in Campo Grande, State of Mato Grosso do Sul.
AB  - INTRODUCTION: The primary strategy for tuberculosis control involves identifying
      individuals with latent tuberculosis. This study aimed to estimate the prevalence
      of latent tuberculosis in chronic kidney disease (CKD) patients who were
      undergoing hemodialysis in Campo Grande, State of Mato Grosso do Sul, Brazil, to
      characterize the sociodemographic and clinical profiles of patients with latent
      tuberculosis, to verify the association between sociodemographic and clinical
      characteristics and the occurrence of latent tuberculosis, and to monitor patient
      adherence to latent tuberculosis treatment. METHODS: This epidemiological study
      involved 418 CKD patients who were undergoing hemodialysis and who underwent a
      tuberculin skin test. RESULTS: The prevalence of latent tuberculosis was 10.3%.
      The mean patient age was 53.43+/-14.97 years, and the patients were predominantly
      men (63.9%). The population was primarily Caucasian (58.6%); half (50%) were
      married, and 49.8% had incomplete primary educations. Previous contact with
      tuberculosis patients was reported by 80% of the participants. Treatment
      adherence was 97.7%. CONCLUSIONS: We conclude that the prevalence of latent
      tuberculosis in our study population was low. Previous contact with patients with
      active tuberculosis increased the occurrence of latent infection. Although
      treatment adherence was high in this study, it is crucial to monitor tuberculosis
      treatment administered to patients in health services to maintain this high rate.

PMID- 24861296
TI  - Association between the degree of physical impairment from leprosy and dependence
      in activities of daily living among the elderly in a health unit in the State of
      Minas Gerais.
AB  - INTRODUCTION: In addition to the common alterations and diseases inherent in the
      aging process, elderly persons with a history of leprosy are particularly
      vulnerable to dependence because of disease-related impairments. OBJECTIVE:
      determine whether physical impairment from leprosy is associated with dependence
      among the elderly. METHODS: An analytical cross-sectional study of elderly
      individuals with a history of leprosy and no signs of cognitive impairment was
      conducted using a database from a former leprosy colony-hospital. The patients
      were evaluated for dependence in the basic activities of daily living (BADL) and
      instrumental activities of daily living (IADL), respectively) and subjected to
      standard leprosy physical disability grading. Subsequently, descriptive and
      univariate analyses were conducted, the latter using Pearson's chi-squared test.
      RESULTS: A total of 186 elderly persons were included in the study. Of these
      individuals, 53.8% were women, 49.5% were older than 75 years of age, 93% had
      four or less years of formal education, 24.2% lived in an institution for the
      long-term care of the elderly (ILTC), and 18.3% had lower limb amputations. Among
      those evaluated, 79.8% had visible physical impairments from leprosy (grade 2),
      83.3% were independent in BADL, and 10.2% were independent in IADL. There was a
      higher impairment grade among those patients who were IADL dependent (p=0.038).
      CONCLUSIONS: The leprosy physical impairment grade is associated with dependence
      for IADL, creating the need for greater social support and systematic monitoring
      by a multidisciplinary team. The results highlight the importance of early
      diagnosis and treatment of leprosy to prevent physical impairment and dependence
      in later years.

PMID- 24861297
TI  - Thrombocytopenia as a surrogate marker of hepatosplenic schistosomiasis in
      endemic areas for Schistosomiasis mansoni.
AB  - INTRODUCTION: This study aimed to evaluate whether a low platelet count is a good
      surrogate marker of hepatosplenic schistosomiasis (HSS) in a rural area of
      Brazil. A small district in southeastern Brazil, with a population of 1,543
      individuals and a 23% prevalence of schistosomiasis, was selected for this
      investigation. METHODS: In July 2012, 384 volunteers were subjected to clinical,
      ultrasonography (US), and laboratory examinations, including stool sample
      analysis. The HSS patients were classified into four groups: Group 1 consisted of
      patients with a spleen >13cm and liver fibrosis; Group 2 consisted of patients
      with a palpable spleen and spleen>13cm measured by US; Group 3 consisted of
      patients with a spleen >13cm measured by US; and Group 4 consisted of patients
      with a palpable spleen. RESULTS: Eight patients were in Group 1 (2.1%), twenty
      one were in Group 2 (5.5%), eight were in Group 3 (2.1%), and eighteen were in
      Group 4 (4.7%). A significant difference in the mean platelet counts was observed
      between the patients with and without HSS (p<0.01). Based on the receiver
      operating characteristic (ROC) curve (platelet count <143,000/mm3), the
      sensitivity was greater than 92% in all groups, and the specificity varied from
      44.4% to 75%. CONCLUSIONS: We concluded that in endemic areas, thrombocytopenia
      demonstrates good sensitivity for detecting HSS and may be used as a screening
      tool to identify patients with HSS.

PMID- 24861298
TI  - Viral epidemiology of respiratory infections among children at a tertiary
      hospital in Southern Brazil.
AB  - INTRODUCTION: This study reports the pediatric epidemiology of respiratory
      syncytial virus (RSV), influenza (IF), parainfluenza (PIV), and adenovirus (ADV)
      at Hospital de Clinicas de Porto Alegre. METHODS: Cases of infection,
      hospitalizations in intensive care units (ICUs), nosocomial infections, and
      lethality rates were collected from 2007 to 2010. RESULTS: RSV accounted for most
      nosocomial infections. Intensive care units admission rates for ADV and RSV
      infections were highest in 2007 and 2010. During 2008-2009, H1N1 and ADV had the
      highest ICU admission rates. ADV had the highest fatality rate during 2007-2009.
      CONCLUSIONS: Each virus exhibited distinct behavior, causing hospitalization,
      outbreaks, or lethality.

PMID- 24861299
TI  - Hybrid capture II and PapilloCheck(r) tests for detection of anal high-risk human
      papillomavirus.
AB  - INTRODUCTION: This study evaluated the level of concordance between hybrid
      capture II (HCII) and PapilloCheck(r) for the detection of high-risk human
      papillomavirus (HPV) in anal samples. METHODS: Anal cell samples collected from
      42 human immunodeficiency virus (HIV)+ patients were analyzed. RESULTS:
      Considering only the 13 high-risk HPV types that are detectable by both tests,
      HCII was positive for 52.3% of the samples, and PapilloCheck(r) was positive for
      52.3%. The level of concordance was 80.9% (Kappa = 0.61). CONCLUSIONS: Good
      concordance was observed between the tests for the detection of high-risk HPV.

PMID- 24861301
TI  - Predictive factors of post-discharge surgical site infections among patients from
      a teaching hospital.
AB  - INTRODUCTION: Surgical site infections (SSIs) often manifest after patients are
      discharged and are missed by hospital-based surveillance. METHODS: We conducted a
      case-reference study nested in a prospective cohort of patients from six surgical
      specialties in a teaching hospital. The factors related to SSI were compared for
      cases identified during the hospital stay and after discharge. RESULTS: Among
      3,427 patients, 222 (6.4%) acquired an SSI. In 138 of these patients, the onset
      of the SSI occurred after discharge. Neurological surgery and the use of steroids
      were independently associated with a greater likelihood of SSI diagnosis during
      the hospital stay. CONCLUSIONS: Our results support the idea of a specialty-based
      strategy for post-discharge SSI surveillance.

PMID- 24861300
TI  - Molecular identification of the agent of Q fever - Coxiella burnetii - in
      domestic animals in State of Rio de Janeiro, Brazil.
AB  - INTRODUCTION: Over the last recent years, the number of Q fever cases have has
      increased throughout the world. An epidemiological investigation was performed in
      the area in which the first molecular documentation of Q fever in Brazil was
      previously reported. METHODS: Indirect immunofluorescence assay (IFA) and PCR of
      Coxiella burnetii targeting the htpAB gene were performed in samples from 14 dogs
      (blood); 1 cat (blood); 10 goats (blood, milk, vaginal swab and anal swab); 3
      sheep (blood); and 2 horses (blood). RESULTS: Two dogs, two sheep and five goats
      were seroreactive. DNA was amplified from 6 milk and 2 blood samples from goats
      and from dogs, respectively. The sequence of the amplicons exhibited 99% sequence
      similarity with the homologous sequence of the htpAB gene of C. burnetii RSA 331
      (GenBank - CP000890). CONCLUSIONS: The results confirm C. burnetii infection in
      animals in Rio de Janeiro and reinforce the need for the surveillance of Q fever
      in Brazil.

PMID- 24861302
TI  - Is autonomic function associated with left ventricular systolic function in
      Chagas heart disease patients undergoing treatment for heart failure?
AB  - INTRODUCTION: The association between cardiac autonomic and left ventricular (LV)
      dysfunction in Chagas disease (ChD) is controversial. METHODS: A standardized
      protocol that includes the Valsalva maneuver, a respiratory sinus arrhythmia
      (RSA) test, and an echocardiographic examination was used. Spearman correlation
      coefficients (rho) were used to investigate associations. RESULTS: The study
      population consisted of 118 ChD patients undergoing current medical treatment,
      with an average LV ejection fraction of 51.4+/-2.6%. The LV ejection fraction and
      diastolic dimension were correlated with the Valsalva index (rho=0.358, p<0.001
      and rho=-0.266, p=0.004, respectively) and the RSA (rho=0.391, p<0.001 and rho=
      0.311, p<0.001, respectively). CONCLUSIONS: The impairment of LV function is
      directly associated with a reduction of cardiac autonomic modulation in ChD.

PMID- 24861303
TI  - Cutaneous and visceral leishmaniasis co-infection in dogs from Rio de Janeiro,
      Brazil: evaluation by specific PCR and RFLP-PCR assays.
AB  - INTRODUCTION: During a diagnostic evaluation of canine visceral leishmaniasis
      (VL), two of seventeen dogs were found to be co-infected by Leishmania (Viannia)
      braziliensis and Leishmania (Leishmania) chagasi. METHODS: Specific polymerase
      chain reaction (PCR) and restriction fragment length polymorphism-PCR (RFLP-PCR)
      assays were performed. RESULTS: PCR assays for Leishmania subgenus identification
      followed by RFLP-PCR analysis in biopsies from cutaneous lesions and the spleen
      confirmed the presence of Leishmania (Viannia) braziliensis and Leishmania
      (Leishmania) chagasi in those fragments. CONCLUSIONS: This report reinforces the
      importance of using serological and molecular techniques in the epidemiological
      surveillance of canine populations in endemic areas in which both diseases are
      known to co-exist. In such cases, a reassessment of the control measures is
      required.

PMID- 24861304
TI  - In vitro antifungal activities of leaf extracts of Lippia alba (Verbenaceae)
      against clinically important yeast species.
AB  - INTRODUCTION: There are few studies reporting the antifungal activities of Lippia
      alba extracts. METHODS: A broth microdilution assay was used to evaluate the
      antifungal effects of Lippia alba extracts against seven yeast species of Candida
      and Cryptococcus. The butanol fraction was investigated by gas chromatography
      mass spectrometry. RESULTS: The butanol fraction showed the highest activity
      against Candida glabrata. The fraction also acted synergistically with
      itraconazole and fluconazole against C. glabrata. The dominant compounds in the
      butanol fraction were 2,2,5-trimethyl-3,4-hexanedione, 3,5-dimethyl-4-octanone
      and hexadecane. CONCLUSIONS: The butanol fraction may be a good candidate in the
      search for new drugs from natural products with antifungal activity.

PMID- 24861305
TI  - Brain schistosomiasis in mice experimentally infected with Schistosoma mansoni.
AB  - INTRODUCTION: Human neuroschistosomiasis has been reported in the literature, but
      the possibility of modeling neuroschistosomiasis in mice is controversial.
      METHODS: In two research laboratories in Brazil that maintain the Schistosoma
      mansoni life cycle in rodents, two mice developed signs of brain disease
      (hemiplegia and spinning), and both were autopsied. RESULTS: S. mansoni eggs,
      both with and without granuloma formation, were observed in the brain and
      meninges of both mice by optical microscopy. CONCLUSIONS: This is the first
      description of eggs in the brains of symptomatic mice that were experimentally
      infected with S. mansoni. An investigation of experimental neuroschistosomiasis
      is now feasible.

PMID- 24861306
TI  - Puerperal brain cryptococcoma in an HIV-negative woman successfully treated with
      fluconazole: a case report.
AB  - Cryptococcus spp. cerebral abscesses are uncommon in immunocompetent subjects.
      The recommended induction treatment is the administration of amphotericin B plus
      flucytosine combined with resection for lesions >=3cm. In this paper, we describe
      an HIV-negative woman diagnosed with a large cryptococcoma in the immediate
      postpartum period. The lesion was not resected, and due to amphotericin B
      intolerance, she received an extended course of fluconazole monotherapy. There
      was no disease recurrence during the 4 years of follow-up. The abrupt onset of
      her symptoms following delivery suggests that she developed a postpartum immune
      reconstitution syndrome. This case also demonstrates that in specific situations
      fluconazole monotherapy can be attempted in immunocompetent patients with
      cryptococcoma. 

PMID- 24861307
TI  - Skin lesions simulating blue toe syndrome caused by prolonged contact with a
      millipede.
AB  - Venomous animals are those that, by means of a hunting and defense mechanism, are
      able to inject their prey with a toxic substance produced in their bodies,
      directly from specialized glands (e.g., tooth, sting, spur) through which the
      poison passes. Millipedes are poisonous animals; they can be harmful to humans,
      and their effects usually manifest as erythematous, purpuric, and cyanotic
      lesions; local pain; and paresthesia. Here, we report a case of skin contact with
      a millipede for 6h resulting in skin lesions similar to blue toe syndrome. 

PMID- 24861308
TI  - Atypical presentation of ocular syphilis in an individual with AIDS.

PMID- 24861309
TI  - Healing with malaria: a brief historical review of malariotherapy for
      neurosyphilis, mental disorders and other infectious diseases.

PMID- 24861310
TI  - Pyroglutamylated amyloid-beta is associated with hyperphosphorylated tau and
      severity of Alzheimer's disease.
AB  - Pyroglutamylated amyloid-beta (pE(3)-Abeta) has been suggested to play a major
      role in Alzheimer's disease (AD) pathogenesis as amyloid-beta (Abeta) oligomers
      containing pE(3)-Abeta might initiate tau-dependent cytotoxicity. We aimed to
      further elucidate the associations among pE(3)-Abeta, full-length Abeta and
      hyperphosphorylated tau (HP-tau) in human brain tissue. We examined 41 post
      mortem brains of both AD (n = 18) and controls. Sections from frontal and
      entorhinal cortices were stained with pE(3)-Abeta, HP-tau and full-length Abeta
      antibodies. The respective loads were assessed using image analysis and western
      blot analysis was performed in a subset of cases. All loads were significantly
      higher in AD, but when using Abeta loads as independent variables only frontal
      pE(3)-Abeta load predicted AD. In frontal and entorhinal cortices pE(3)-Abeta
      load independently predicted HP-tau load while non-pE(3)-Abeta failed to do so.
      All loads correlated with the severity of AD neuropathology. However, partial
      correlation analysis revealed respective correlations in the frontal cortex only
      for pE(3)-Abeta load only while in the entorhinal cortex respective correlations
      were seen for both HP-tau and non-pE(3)-Abeta loads. Mini Mental State
      Examination scores were independently predicted by entorhinal HP-tau load and by
      frontal pE(3)-Abeta load. Here, we report an association between pE(3)-Abeta and
      HP-tau in human brain tissue and an influence of frontal pE(3)-Abeta on both the
      severity of AD neuropathology and clinical dementia. Our findings further support
      the notion that pE(3)-Abeta may represent an important link between Abeta and HP
      tau, and investigations into its role as diagnostic and therapeutic target in AD
      are warranted.

PMID- 24861311
TI  - Enhancement of tannase production by Lactobacillus plantarum CIR1: validation in
      gas-lift bioreactor.
AB  - The optimization of tannase production by Lactobacillus plantarum CIR1 was
      carried out following the Taguchi methodology. The orthogonal array employed was
      L18 (2(1) * 3(5)) considering six important factors (pH and temperature, also
      phosphate, nitrogen, magnesium, and carbon sources) for tannase biosynthesis. The
      experimental results obtained from 18 trials were processed using the software
      Statistical version 7.1 using the character higher the better. Optimal culture
      conditions were pH, 6; temperature, 40  degrees C; tannic acid, 15.0 g/L; KH2PO4,
      1.5 g/L; NH4Cl, 7.0 g/L; and MgSO4, 1.5 g/L which were obtained and further
      validated resulting in an enhance tannase yield of 2.52-fold compared with
      unoptimized conditions. Tannase production was further carried out in a 1-L gas
      lift bioreactor where two nitrogen flows (0.5 and 1.0 vvm) were used to provide
      anaerobic conditions. Taguchi methodology allowed obtaining the optimal culture
      conditions for the production of tannase by L. plantarum CIR1. At the gas-lift
      bioreactor the tannase productivity yields increase 5.17 and 8.08-fold for the
      flow rates of 0.5 and 1.0 vvm, respectively. Lactobacillus plantarum CIR1 has the
      capability to produce tannase at laboratory-scale. This is the first report for
      bacterial tannase production using a gas-lift bioreactor. 

PMID- 24861312
TI  - Start-up and operation strategies on the liquefied food waste anaerobic digestion
      and a full-scale case application.
AB  - Batch anaerobic digestion was employed to investigate the efficient start-up
      strategies for the liquefied food waste, and sequencing batch digestion was also
      performed to determine maximum influent organic loading rate (OLR) for efficient
      and stable operation. The results indicated that the start-up could be well
      improved using appropriate wastewater organic load and food-to-microorganism
      ratios (F/M). When digestion was initialized at low chemical oxygen demand (COD)
      concentration of 20.0 gCOD L(-1), the start-up would go well using lower F/M
      ratio of 0.5-0.7. The OLR 7.0 gCOD L(-1) day(-1) was recommended for operating
      the ASBR digestion, in which the COD conversion of 96.7 +/- 0.53% and biomethane
      yield of 3.5 +/- 0.2 L gCOD(-1) were achieved, respectively. The instability
      would occur when OLR was higher than 7.0 gCOD L(-1) day(-1), and this instability
      was not recoverable. Lipid was suggested to be removed before anaerobic
      digestion. The anaerobic digestion process in engineering project ran well, and
      good performance was achieved when the start-up and operational strategies from
      laboratory study were applied. For case application, stable digestion performance
      was achieved in a digester (850 m(3) volume) with biogas production of 1.0-3.8
      m(3) m(-3) day(-1).

PMID- 24861313
TI  - Screening of phenylpyruvic acid producers and optimization of culture conditions
      in bench scale bioreactors.
AB  - Alpha keto acids are deaminated forms of amino acids that have received
      significant attention as feed and food additives in the agriculture and medical
      industries. To date, their production has been commonly performed at shake-flask
      scale with low product concentrations. In this study, production of phenylpyruvic
      acid (PPA), which is the alpha keto acid of phenylalanine was investigated.
      First, various microorganisms were screened to select the most efficient
      producer. Thereafter, growth parameters (temperature, pH, and aeration) were
      optimized in bench scale bioreactors to maximize both PPA and biomass
      concentration in bench scale bioreactors, using response surface methodology.
      Among the four different microorganisms evaluated, Proteus vulgaris was the most
      productive strain for PPA production. Optimum temperature, pH, and aeration
      conditions were determined as 34.5  degrees C, 5.12, and 0.5 vvm for PPA
      production, whereas 36.9  degrees C, pH 6.87, and 0.96 vvm for the biomass
      production. Under these optimum conditions, PPA concentration was enhanced to
      1,054 mg/L, which was almost three times higher than shake-flask fermentation
      concentrations. Moreover, P. vulgaris biomass was produced at 3.25 g/L under
      optimum conditions. Overall, this study demonstrated that optimization of growth
      parameters improved PPA production in 1-L working volume bench-scale bioreactors
      compared to previous studies in the literature and was a first step to scale up
      the production to industrial production. 

PMID- 24861314
TI  - Multiplying steady-state culture in multi-reactor system.
AB  - Cultivation of microorganisms in batch experiments is fast and economical but the
      conditions therein change constantly, rendering quantitative data interpretation
      difficult. By using chemostat with controlled environmental conditions the
      physiological state of microorganisms is fixed; however, the unavoidable
      stabilization phase makes continuous methods resource consuming. Material can be
      spared by using micro scale devices, which however have limited analysis and
      process control capabilities. Described herein are a method and a system
      combining the high throughput of batch with the controlled environment of
      continuous cultivations. Microorganisms were prepared in one bioreactor followed
      by culture distribution into a network of bioreactors and continuation of
      independent steady state experiments therein. Accelerostat cultivation with
      statistical analysis of growth parameters demonstrated non-compromised
      physiological state following distribution, thus the method effectively
      multiplied steady state culture of microorganisms. The theoretical efficiency of
      the system was evaluated in inhibitory compound analysis using repeated chemostat
      to chemostat transfers. 

PMID- 24861315
TI  - Influence of physical and chemical properties of HTSXT-FTIR samples on the
      quality of prediction models developed to determine absolute concentrations of
      total proteins, carbohydrates and triglycerides: a preliminary study on the
      determination of their absolute concentrations in fresh microalgal biomass.
AB  - Absolute concentrations of total macromolecules (triglycerides, proteins and
      carbohydrates) in microorganisms can be rapidly measured by FTIR spectroscopy,
      but caution is needed to avoid non-specific experimental bias. Here, we assess
      the limits within which this approach can be used on model solutions of
      macromolecules of interest. We used the Bruker HTSXT-FTIR system. Our results
      show that the solid deposits obtained after the sampling procedure present
      physical and chemical properties that influence the quality of the absolute
      concentration prediction models (univariate and multivariate). The accuracy of
      the models was degraded by a factor of 2 or 3 outside the recommended
      concentration interval of 0.5-35 ug spot(-1). Change occurred notably in the
      sample hydrogen bond network, which could, however, be controlled using an
      internal probe (pseudohalide anion). We also demonstrate that for aqueous
      solutions, accurate prediction of total carbohydrate quantities (in glucose
      equivalent) could not be made unless a constant amount of protein was added to
      the model solution (BSA). The results of the prediction model for more complex
      solutions, here with two components: glucose and BSA, were very encouraging,
      suggesting that this FTIR approach could be used as a rapid quantification method
      for mixtures of molecules of interest, provided the limits of use of the HTSXT
      FTIR method are precisely known and respected. This last finding opens the way to
      direct quantification of total molecules of interest in more complex matrices. 

PMID- 24861316
TI  - A comparative ecotoxicity analysis of alpha- and gamma-phase aluminium oxide
      nanoparticles towards a freshwater bacterial isolate Bacillus licheniformis.
AB  - Crystalline structure of nanoparticles may influence their physicochemical
      behaviour as well as their toxicological impact on biota. The differences in
      orientation of the atoms result in the variations in chemical stability. Thus,
      toxicological impacts of different crystalline phases of aluminium oxide
      nanoparticles are expected to vary. The present study brings out a comparative
      toxicity analysis of gamma-phase and alpha-phase aluminium oxide nanoparticles of
      comparable hydrodynamic size range towards a freshwater bacterial isolate
      Bacillus licheniformis at low exposure concentrations (5, 1, 0.5 and 0.05 ug/mL).
      Upon 2-h exposure, the alpha-aluminium oxide particles showed lower toxicity than
      the gamma-phase aluminium oxide. The lower level of oxidative stress generation
      and cell membrane damage in case of the alpha-phase aluminium oxide nanoparticles
      substantiated the toxicity results. The involvement of protein,
      lipopolysaccharides in nanoparticle-cell surface interaction, was noted in both
      the cases. To conclude, the crystallinity of aluminium oxide nanoparticles played
      an important role in the interaction and the toxicity response. 

PMID- 24861317
TI  - Small molecules differentiate definitive endoderm from human induced pluripotent
      stem cells on PCL scaffold.
AB  - Human induced pluripotent stem cells (hiPSCs) are attractive sources of cells for
      disease modeling in vitro, and they may eventually provide access to
      cells/tissues for the treatment of many degenerative diseases. Stepwise
      differentiation from hiPSCs to definitive endoderm (DE) will identify a key step
      in hepatocytes and beta cell development and may prove useful for transplantation
      therapy for liver diseases and diabetes. Inducer of definitive endoderm 1 (IDE1)
      is known to play an important role in the regional specification of DE. Here, we
      have investigated the effect of stimulation with IDE1 on the development of
      hiPSCs into DE cells in three-dimensional (3D) cultures. The differentiation was
      determined by immunofluorescence staining with Sox17, FoxA2, and goosecoid (Gsc)
      and also by quantitative reverse transcriptase-polymerase chain reaction (qRT
      PCR) analysis. In this study, we showed that hiPSCs with 6-day IDE1 treatment (as
      chemical tool) on poly(epsilon-caprolactone) (PCL) nanofibrous scaffold were able
      to differentiate into DE cells. 

PMID- 24861318
TI  - The yjjN of E. coli codes for an L-galactonate dehydrogenase and can be used for
      quantification of L-galactonate and L-gulonate.
AB  - Escherichia coli is able to utilize L-galactonate as a sole carbon source. A
      metabolic pathway for L-galactonate catabolism is described in E. coli, and it is
      known to be interconnected with D-galacturonate metabolism. The corresponding
      gene encoding the first enzyme in the L-galactonate pathway, L-galactonate-5
      dehydrogenase, was suggested to be yjjN. However, L-galactonate dehydrogenase
      activity was never demonstrated with the yjjN gene product. Here, we show that
      YjjN is indeed an L-galactonate dehydrogenase having activity also for L
      gulonate. The K m and k cat for L-galactonate were 19.5+/-0.6 mM and 0.51+/-0.03
      s(-1), respectively. In addition, YjjN was applied for a quantitative detection
      of the both of these substances in a coupled assay. The detection limits for L
      galactonate and L-gulonate were 1.65 and 10 MUM, respectively.

PMID- 24861319
TI  - Expression, purification, and characterization of NADP+-dependent malic enzyme
      from the oleaginous fungus Mortierella alpina.
AB  - Malic enzymes are a class of oxidative decarboxylases that catalyze the oxidative
      decarboxylation of malate to pyruvate and carbon dioxide, with concomitant
      reduction of NAD(P)+ to NAD(P)H. The NADP+-dependent malic enzyme in oleaginous
      fungi plays a key role in fatty acid biosynthesis. In this study, the malic
      enzyme-encoding complementary DNA (cDNA) (malE1) from the oleaginous fungus
      Mortierella alpina was cloned and expressed in Escherichia coli BL21 (DE3). The
      recombinant protein (MaME) was purified using Ni-NTA affinity chromatography. The
      purified enzyme used NADP+ as the cofactor. The K m values for L-malate and NADP+
      were 2.19+/-0.01 and 0.38+/-0.02 mM, respectively, while the V max values were
      147+/-2 and 302+/-14 U/mg, respectively, at the optimal condition of pH 7.5 and
      33  degrees C. MaME is active in the presence of Mn2+, Mg2+, Co2+, Ni2+, and low
      concentrations of Zn2+ rather than Ca2+, Cu2+, or high concentrations of Zn2+.
      Oxaloacetic acid and glyoxylate inhibited the MaME activity by competing with
      malate, and their K i values were 0.08 and 0.6 mM, respectively.

PMID- 24861320
TI  - A mathematical analysis of the selective enrichment of NECEEM-based non-SELEX.
AB  - Non-Systematic Evolution of Ligands by EXponential enrichment (SELEX)selection of
      aptamers, a novel technology for aptamer selection from libraries of random DNA
      (or RNA) sequences, involves repetitive steps of partitioning without polymerase
      chain reaction (PCR) amplification between them. This selection is based on non
      equilibrium capillary electrophoresis of equilibrium mixtures (NECEEM) and has
      exceptionally high efficiency. In this paper, a mathematical analysis was carried
      out to predict the levels of enrichment of non-SELEX selection under different
      conditions such as different protein concentrations and different efficiencies of
      partitioning. Investigated results suggest that the magnitude of the bulk
      affinity (k d) being 10(4) or 10(5) MUM for the initial pool has no obvious
      effect on selective enrichment and that the first, second, and third rounds of
      non-SELEX selection have different optimum protein concentration values [T f]
      that give maximum enrichment levels when [T f] ranges from 0.0005 to 0.5 MUM. The
      significance of analyzing selective enrichment of NECEEM-based non-SELEX with the
      efficiency of partitioning target-bound ligands from free ligands has been
      demonstrated.

PMID- 24861321
TI  - Use of flavins as catalyst for the remediation of halogenated compounds.
AB  - Flavin-containing monooxygenases (FMOs) are an important monooxygenase system
      present in living organisms starting from eukaryotes to human beings. They are
      involved in catalysing wide variety of oxygenation reactions including
      bioremediation process. The central reaction in these enzymes is always the
      formation of a peroxyflavin intermediate by reaction of reduced flavin with
      molecular oxygen. The microenvironment of the peroxyflavin regulates the reactive
      character of the peroxyflavin. Utilizing this aspect of the biology,
      chemremediation of aromatic halogenated phenols have been initiated and achieved
      using flavinium perchlorate salt as catalyst in 38 % yield. The flavinium
      perchlorate during the reaction gets converted to peroxyflavin with H2O2. This
      method will be useful in the removal of halogens from aromatic halogenated
      phenols. 

PMID- 24861322
TI  - Encapsulation of 3-iodo-2-propynyl N-butylcarbamate (IPBC) in polystyrene
      polycaprolactone (PS/PCL) blends.
AB  - Polystyrene (PS, 1), polycaprolactone homopolymers (PCL, 2) and 3-Iodo-2-propynyl
      n-butylcarbamate (IPBC, 3) were physically mixed in dichloromethane (DCM) and
      processed into solid microspheres by using emulsion solvent evaporation method.
      Five different compositions with varying PS/PCL ratio were tested. The phase
      morphology of the microspheres was studied using Phase imaging atomic force
      microscopy (AFM) of polished cross-sections. Scanning electron microscopy was
      utilized to assess the distribution of IPBC in the polymer microspheres. The
      phase separation of the PS and PCL polymers in solvent cast films was assessed
      using polarized light optical microscopy of 11 polymer blends (0-100 wt-% PCL in
      PS). The PS/PCL-IPBC microspheres were incubated in water at RT and the release
      of IPBC was studied using high performance liquid chromatography (HPLC) at time
      points 1, 7 and 30 days. The microspheres dispersed in water borne outdoor paint
      matrix were tested for their antifouling activity against moulds in vitro.

PMID- 24861323
TI  - The effect of surfactant composition on the chemical and structural properties of
      nanostructured lipid carriers.
AB  - Fine-tuning the nanoscale structure and morphology of nanostructured lipid
      carriers (NLCs) is central to improving drug loading and stability of the
      particles. The role of surfactant charge on controlling the structure, the
      physicochemical properties and the stability of NLCs has been investigated using
      three surfactant types (cationic, anionic, non-ionic), and mixed surfactants.
      Either one, a mixture of two, or a mixture of three surfactants were used to coat
      the NLCs, with these classified as one, two and three surfactant systems,
      respectively. The mixed (two and three) surfactant systems produced smaller NLC
      particles and yielded NLCs with lower crystallinity than the one surfactant
      system. The combined effects of the ionic and the non-ionic surfactants may play
      a key role in assisting the lipid-oil mixing, as well as maintaining colloidal
      repulsion between NLC particles. In contrast, for the three surfactant system,
      the lipid-oil mixture in the NLCs appeared less homogenous. This was also
      reflected in the results of the stability study, which indicated that NLC
      particle sizes in two surfactant systems appeared to be retained over longer
      periods than for other surfactant systems.

PMID- 24861324
TI  - Preparation of naproxen-ethyl cellulose microparticles by spray-drying technique
      and their application to textile materials.
AB  - The objective of this study is to develop a new textile-based drug delivery
      system containing naproxen (NAP) microparticles and to evaluate the potential of
      the system as the carrier of NAP for topical delivery. Microparticles were
      prepared by spray-drying using an aqueous ethyl cellulose dispersion. The drug
      content and entrapment efficiency, particle size and distribution, particle
      morphology and in vitro drug release characteristics of microparticles were
      optimized for the application of microparticles onto the textile fabrics.
      Microparticles had spherical shape in the range of 10-15 MUm and a narrow
      particle size distribution. NAP encapsulated in microparticles was in the
      amorphous or partially crystalline nature. Microparticles were tightly fixed onto
      the textile fabrics. In vitro drug release exhibited biphasic release profile
      with an initial burst followed by a very slow release. Skin permeation profiles
      were observed to follow near zero-order release kinetics.

PMID- 24861325
TI  - Participants' perceived benefits of family intervention following a first episode
      of psychosis: a qualitative study.
AB  - AIM: To explore the perceived benefits for patients and family members of
      psychoeducational family intervention following a first episode of psychosis.
      METHODS: A qualitative exploratory study using data from interviews with 12
      patients and 14 family members who participated in a psychoeducational multi- or
      single-family treatment programme. Semi-structured interviews were digitally
      recorded and transcribed verbatim with slight modifications, after which they
      were analysed by systematic text condensation. RESULTS: Patients and family
      members reported benefits that could be classified in five categories: (i)
      developing insight and acceptance requires understanding of the fact that the
      patient has an illness, and recognizing the need for support; (ii) recognizing
      warning signs requires an understanding of early signs of deterioration in the
      patient; (iii) improving communication skills is linked to new understanding and
      better communication both within the family and in groups; (iv) Learning to plan
      and solve problems requires the ability to solve problems in new ways; (v)
      becoming more independent requires patients to take responsibility for their own
      life. CONCLUSION: The study suggests that developing insight and acceptance,
      learning about warning signs, improving communications skills, learning to plan
      and solve problems, and becoming more independent are perceived as benefits of a
      psychoeducational family intervention.

PMID- 24861326
TI  - Testicular cancer: identifying occult metastatic seminoma using two small RNAs.

PMID- 24861327
TI  - Bladder cancer: Accelerating MVAC.

PMID- 24861329
TI  - Prostate cancer: primary ADT monotherapy not suitable for localized disease.
AB  - Although current guidelines do not endorse the use of primary androgen
      deprivation therapy (PADT) as monotherapy for localized prostate cancer, many
      patients continue to receive this treatment. New outcomes research confirms that
      there is no clear reason for use of PADT in men with localized prostate cancer.

PMID- 24861331
TI  - Prostate cancer: European urologists prefer surgery for high-risk prostate
      cancer.

PMID- 24861332
TI  - Prostate cancer: mixed responses to ipilimumab.

PMID- 24861334
TI  - Imaging: routine imaging unnecessary after blunt renal trauma.

PMID- 24861336
TI  - Temporary insertion of a covered self-expandable metal stent for spontaneous
      esophageal rupture.

PMID- 24861338
TI  - Toxoplasma gondii- derived profilin triggers human toll-like receptor 5-dependent
      cytokine production.
AB  - Up to a third of the world's population is infected with Toxoplasma gondii.
      Natural infection in humans can be life threatening during pregnancy and in
      immunocompromised individuals. Toll-like receptor (TLR) 11 is the mouse innate
      sensor that recognizes T. gondii profilin; however, in humans the TLR11 gene
      leads to transcription of no functional protein. Herein, by using a multiple
      sequence alignment phylogenetic analysis program between human and mouse species,
      we found that human TLR5 seems to be the evolutionarily closest member of the TLR
      gene family to mouse tlr11. We therefore asked whether human TLR5 could mediate
      IL-6, IL-8 and IL-12p70 production in response to the T. gondii profilin. We
      found that this was the case both in human cell lines as well as peripheral blood
      monocytes. Moreover, TLR5 neutralization and gene silencing mediated specific
      ablation of cytokine production after profilin exposure. Finally, peripheral
      blood monocytes carrying the TLR5 R392X mutation failed to produce cytokines in
      response to stimulation with profilin. Taken together, the results presented
      herein reveal a previously unappreciated cross-recognition of a relevant human
      pathogen-derived pathogen-associated molecular pattern.

PMID- 24861340
TI  - The intergenerational transmission of intimate partner violence in Bangladesh.
AB  - BACKGROUND: A number of individual risk factors for intimate partner violence
      (IPV) have been identified in Bangladesh. However, the etiology of IPV,
      intergenerational transmission, has never been tested in Bangladesh. OBJECTIVE:
      We examined whether witnessing inter-parental physical violence (IPPV) was
      associated with IPV to identify whether IPV passes across generations in
      Bangladesh. METHODS: We used nationally representative data of currently married
      women from the Bangladesh Demographic and Health Survey-2007. Variations in
      experiencing IPV were assessed by Chi-square tests. Logistic regression models
      were fit to determine the association between witnessing IPPV and different types
      of IPV against women. RESULTS: One-fourth of women witnessed IPPV and experienced
      IPV. After adjusting for the covariates, women who witnessed IPPV were 2.4 (95%
      confidence interval [CI]: 2.0-2.8) times more likely to experience any kind of
      IPV, 2.5 (95% CI: 2.0-3.0) times more likely to experience moderate physical IPV,
      2.3 (95% CI: 1.8-3.0) times more likely to experience severe physical IPV, and
      1.8 (95% CI: 1.4-2.3) times more likely to experience sexual IPV. Age, age at
      first marriage, literacy, work status, wealth, justified wife beating, and
      women's autonomy were also identified as significant correlates of IPV.
      CONCLUSIONS: This study's results indicate that IPV passes from one generation to
      another. We make recommendations for preventing IPPV so that subsequent
      generations can enjoy healthy, respectful, nonviolent relationships in married
      life without exposure to IPV in Bangladesh.

PMID- 24861339
TI  - Risk of birth defects associated with maternal pregestational diabetes.
AB  - Maternal diabetes preceding pregnancy may increase the risk of birth defects in
      the offspring, but not all studies confirm this association, which has shown
      considerable variation over time, and the effect of having type 1 versus type 2
      diabetes is unclear. We conducted a population-based cohort study in the Northern
      Italy Emilia-Romagna region linking administrative databases with a Birth Defects
      Registry. From hospital discharge records we identified all diabetic pregnancies
      during 1997-2010, and a population of non-diabetic parturients matched for age,
      residence, year and delivery hospital. We collected available information on
      education, smoking and drug prescriptions, from which we inferred the type of
      diabetes. We found 62 malformed infants out of 2,269 births among diabetic women,
      and 162 out of 10,648 births among non-diabetic women. The age-standardized
      prevalence ratio (PR) of malformation associated with maternal pregestational
      diabetes was 1.79 (95 % confidence interval 1.34-2.39), a value that varied
      little by age. Type of diabetes strongly influenced the PR, with higher values
      related to type 2 diabetic women. Most major subgroups of anomalies had PRs above
      1, including cardiovascular, genitourinary, musculoskeletal, and chromosomal
      abnormalities. There was an unusually high PR for the rare defect 'extra-ribs',
      but it was based on only two cases. This study indicates that maternal
      pregestational type 2 diabetes is associated with a higher prevalence of specific
      birth defects in offspring, whereas for type 1 diabetic mothers, particularly in
      recent years, the association was unremarkable.

PMID- 24861341
TI  - Climate change and health modeling: horses for courses.
AB  - Mathematical and statistical models are needed to understand the extent to which
      weather, climate variability, and climate change are affecting current and may
      affect future health burdens in the context of other risk factors and a range of
      possible development pathways, and the temporal and spatial patterns of any
      changes. Such understanding is needed to guide the design and the implementation
      of adaptation and mitigation measures. Because each model projection captures
      only a narrow range of possible futures, and because models serve different
      purposes, multiple models are needed for each health outcome ('horses for
      courses'). Multiple modeling results can be used to bracket the ranges of when,
      where, and with what intensity negative health consequences could arise. This
      commentary explores some climate change and health modeling issues, particularly
      modeling exposure-response relationships, developing early warning systems,
      projecting health risks over coming decades, and modeling to inform decision
      making. Research needs are also suggested. 

PMID- 24861342
TI  - Biocontrol traits and antagonistic potential of Bacillus amyloliquefaciens strain
      NJZJSB3 against Sclerotinia sclerotiorum, a causal agent of canola stem rot.
AB  - Bacillus amyloliquefaciens strain NJZJSB3 has shown antagonism of several
      phytopathogens in vitro, especially Sclerotinia sclerotiorum. Both the broth
      culture and cell suspension of strain NJZJSB3 could completely protect the
      detached leaves of canola (Brassica napus) from S. sclerotiorum infection. In pot
      experiments, the application of strain NJZJSB3 cell suspension (10(8) CFU/ml)
      decreased the disease incidence by 83.3%, a result similar to commercially
      available fungicide (Dimetachlone). In order to investigate the potential
      biocontrol mechanisms of strain NJZJSB3, the nonvolatile antifungal compounds it
      produces were identified as iturin homologs using HPLC-ESI-MS. Antifungal
      volatile organic compounds were identified by gas chromatography-mass
      spectrometry. The detected volatiles toluene, phenol, and benzothiazole showed
      antifungal effects against S. sclerotiorum in chemical control experiments.
      Strain NJZJSB3 also produced biofilm, siderophores and cell-wall-degrading
      enzymes (protease and beta-1,3-glucanase). These results suggest that strain
      NJZJSB3 can be a tremendous potential agent for the biological control of
      sclerotinia stem rot.

PMID- 24861337
TI  - Perispinal etanercept for post-stroke neurological and cognitive dysfunction:
      scientific rationale and current evidence.
AB  - There is increasing recognition of the involvement of the immune signaling
      molecule, tumor necrosis factor (TNF), in the pathophysiology of stroke and
      chronic brain dysfunction. TNF plays an important role both in modulating
      synaptic function and in the pathogenesis of neuropathic pain. Etanercept is a
      recombinant therapeutic that neutralizes pathologic levels of TNF. Brain imaging
      has demonstrated chronic intracerebral microglial activation and
      neuroinflammation following stroke and other forms of acute brain injury.
      Activated microglia release TNF, which mediates neurotoxicity in the stroke
      penumbra. Recent observational studies have reported rapid and sustained
      improvement in chronic post-stroke neurological and cognitive dysfunction
      following perispinal administration of etanercept. The biological plausibility of
      these results is supported by independent evidence demonstrating reduction in
      cognitive dysfunction, neuropathic pain, and microglial activation following the
      use of etanercept, as well as multiple studies reporting improvement in stroke
      outcome and cognitive impairment following therapeutic strategies designed to
      inhibit TNF. The causal association between etanercept treatment and reduction in
      post-stroke disability satisfy all of the Bradford Hill Criteria: strength of the
      association; consistency; specificity; temporality; biological gradient;
      biological plausibility; coherence; experimental evidence; and analogy.
      Recognition that chronic microglial activation and pathologic TNF concentration
      are targets that may be therapeutically addressed for years following stroke and
      other forms of acute brain injury provides an exciting new direction for research
      and treatment. 

PMID- 24861343
TI  - Prevalence and genotype distribution of human papillomavirus in Cheonan, Korea.
AB  - Human papillomavirus (HPV) infection is considered to play a critical role in the
      development of cervical carcinoma, which is the third most common cancer among
      Korean females. Here, we performed a baseline study of HPV infection and
      genotyping using an HPV DNA chip, which is a type of oligonucleotide microarray.
      A total of 6,855 cervical swab specimens from 5,494 women attending Dankook
      University Hospital Health Improvement Center in Cheonan, Korea between 2006 and
      2012, originally collected for HPV infection screening, were genotyped for HPV.
      The extracted DNA from the cervical specimens was investigated by an HPV DNA chip
      designed to detect 41 different HPV types. HPV was identified as positive in
      1,143 (16.7%) of the 6,855 samples. The most frequently detected HPV genotypes
      were HPV types 16, 53, 56, 58, 39, 52, 70, 84, 68, 62, 35, 54, 81, 18, and 30, in
      descending order of incidence. The proportions of single and multiple HPV
      infections in the HPV-positive specimens were 78.1% and 21.9%, respectively. The
      average age of HPV-positive patients was 39.9 years, with the positive rate of
      HPV being the highest in the 10-29 age group (20.6%). We report here on the
      prevalence and distribution of 41 different genotypes of HPV according to age
      among women in Cheonan, Korea. These data may be of use as baseline data for the
      assessment of public health-related issues and for the development of area
      specific HPV vaccines. 

PMID- 24861344
TI  - Biochemical characterization of L-asparaginase in NaCl-tolerant Staphylococcus
      sp. OJ82 isolated from fermented seafood.
AB  - L-Asparaginase from gram-positive bacteria has been poorly explored. We conducted
      recombinant overexpression and purification of L-asparaginase from Staphylococcus
      sp. OJ82 (SoAsn) isolated from Korean fermented seafood to evaluate its
      biotechnological potential as an antileukemic agent. SoAsn was expressed in
      Escherichia coli BL21 (DE3) with an estimated molecular mass of 37.5 kDa,
      determined using sodium dodecyl sulfate-polyacrylamide gel electrophoresis.
      Consistent with asparaginases in gram-negative bacteria, size-exclusion
      chromatography determined SoAsn as a homodimer. Interestingly, the optimal
      temperature of SoAsn was 37 degrees C and over 90% of activity was retained
      between 37 degrees C and 50 degrees C, and its thermal stability range was
      narrower than that of commercial E. coli L-asparaginase (EcAsn). Both SoAsn and
      EcAsn were active between pH 9 and 10, although their overall pH-dependent enzyme
      activities were slightly different. The Km value of SoAsn was 2.2 mM, which is
      higher than that of EcAsn. Among eight metals tested for enzyme activity, cobalt
      and magnesium greatly enhanced the SoAsn and EcAsn activity, respectively.
      Interestingly, SoAsn retained more than 60% of its activity under 2 M NaCl
      condition, but the activity of EcAsn was reduced to 48%. Overall, the biochemical
      characteristics of SoAsn were similar to those of EcAsn, but its kinetics,
      cofactor requirements, and NaCl tolerance differed from those of EcAsn.

PMID- 24861345
TI  - Gut microbiota of Tenebrio molitor and their response to environmental change.
AB  - A bacterial community analysis of the gut of Tenebrio molitor larvae was
      performed using pyrosequencing of the 16S rRNA gene. A predominance of genus
      Spiroplasma species in phylum Tenericutes was observed in the gut samples, but
      there was variation found in the community composition between T. molitor
      individuals. The gut bacteria community structure was not significantly affected
      by the presence of antibiotics or by the exposure of T. molitor larvae to a
      highly diverse soil bacteria community. A negative relationship was identified
      between bacterial diversity and ampicillin concentration; however, no negative
      relationship was identified with the addition of kanamycin. Ampicillin treatment
      resulted in a reduction in the bacterial community size, estimated using the 16S
      rRNA gene copy number. A detailed phylogenetic analysis indicated that the
      Spiroplasma-associated sequences originating from the T. molitor larvae were
      distinct from previously identified Spiroplasma type species, implying the
      presence of novel Spiroplasma species. Some Spiroplasma species are known to be
      insect pathogens; however, the T. molitor larvae did not experience any harmful
      effects arising from the presence of Spiroplasma species, indicating that
      Spiroplasma in the gut of T. molitor larvae do not act as a pathogen to the host.
      A comparison with the bacterial communities found in other insects (Apis and
      Solenopsis) showed that the Spiroplasma species found in this study were specific
      to T. molitor. 

PMID- 24861347
TI  - Colistin, SDD and resistance: nihil novi sub sole.

PMID- 24861346
TI  - Novel alkali-tolerant GH10 endo-beta-1,4-xylanase with broad substrate
      specificity from Microbacterium trichothecenolyticum HY-17, a gut bacterium of
      the mole cricket Gryllotalpa orientalis.
AB  - The XylH gene (1,167-bp) encoding a novel hemicellulase (41,584 Da) was
      identified from the genome of Microbacterium trichothecenolyticum HY-17, a
      gastrointestinal bacterium of Gryllotalpa orientalis. The enzyme consisted of a
      single catalytic domain, which is 74% identical to that of an endo-beta-1,4
      xylanase (GH10) from Isoptericola variabilis 225. Unlike other endo-beta- 1,4
      xylanases from invertebrate-symbiotic bacteria, rXylH was an alkali-tolerant
      multifunctional enzyme possessing endo-beta-1,4-xylanase activity together with
      beta-1,3/beta-1,4- glucanase activity, which exhibited its highest xylanolytic
      activity at pH 9.0 and 60 degrees C, and was relatively stable within a broad pH
      range of 5.0-10.0. The susceptibilities of different xylosebased polysaccharides
      to the XylH were assessed to be as follows: oat spelts xylan > beechwood xylan >
      birchwood xylan > wheat arabinoxylan. rXylH was also able to readily cleave p
      nitrophenyl (pNP) cellobioside and pNP-xylopyranoside, but did not hydrolyze
      other pNP-sugar derivatives, xylobiose, or hexose-based materials. Enzymatic
      hydrolysis of birchwood xylan resulted in the product composition of xylobiose
      (71.2%) and xylotriose (28.8%) as end products. 

PMID- 24861348
TI  - Therapeutic hypothermia and coronary angiography are mandatory after out-of
      hospital cardiac arrest: Yes.

PMID- 24861349
TI  - SDD and colistin resistance: end of a dream?

PMID- 24861350
TI  - Weaning-induced cardiac dysfunction: where are we today?
AB  - INTRODUCTION: The concept of weaning-induced cardiac dysfunction emerged 26 years
      ago with the publication of a clinical study conducted by Francois Lemaire and
      collaborators. OBJECTIVES: One objective of this article is to remember the
      results and the historical context under which our pivotal study was conducted.
      Another objective is to review some of the subsequent studies that aimed to
      analyze the underlying mechanisms, to noninvasively detect the cardiac origin of
      weaning failure, and to propose specific therapies enabling weaning success.
      CONCLUSION: Weaning-induced cardiac dysfunction has become an established cause
      of weaning failure. Underlying mechanisms may differ from one patient to another.
      Important progress has already been made in its diagnosis thanks to relevant
      clinical research studies. Ongoing and future technological advances in
      ultrasonography and in biomarker research should certainly help in diagnosing
      weaning induced-pulmonary edema and in identifying the main mechanisms
      responsible for its development. Progress on appropriate therapeutic options on
      an individual basis is still expected.

PMID- 24861352
TI  - Voice problems among laryngopharyngeal reflux patients diagnosed with
      oropharyngeal pH monitoring.
AB  - BACKGROUND AND OBJECTIVES: There is a lack of consensus regarding the clinical
      presentation and diagnosis of laryngopharyngeal reflux (LPR). The aim of this
      study was to explore voice-related abnormalities in a group of LPR patients,
      diagnosed with a 24-hour oropharyngeal pH monitoring. PATIENTS AND METHODS:
      Eighty-two patients with voice-related problems participated in the study.
      Diagnosis of LPR was made using a 24-hour oropharyngeal pH monitoring. Patients
      were divided accordingly into positive and negative pH groups. Comparisons
      between the two groups were done, including results of clinical presentation,
      Voice Handicap Index-10 (VHI-10), reflux symptom index (RSI), reflux finding
      score (RFS), and acoustic measurements. The correlation was conducted between
      Ryan scores and other variables including VHI-10, RSI, and RFS. RESULTS:
      Significant differences were found between the two groups for RSI and VHI-10. No
      significant differences were found between the two groups regarding clinical
      presentation, RFS or acoustic measures. Significant positive correlations were
      found between the Ryan composite measurements and both severity ratings (VHI-10,
      RSI). CONCLUSION: LPR clinical presentation appears to be non-specific in terms
      of symptoms and laryngeal findings. LPR appears to have an effect on the
      patients' self-perception of voice problems. Further studies are needed to
      clarify the effect of LPR on acoustic measurements.

PMID- 24861353
TI  - Limited sampling strategies for tacrolimus exposure (AUC0-24) prediction after
      Prograf((r)) and Advagraf((r)) administration in children and adolescents with
      liver or kidney transplants.
AB  - To develop limited sampling strategies (LSSs) to predict total tacrolimus
      exposure (AUC0-24 ) after the administration of Advagraf((r)) and Prograf((r))
      (Astellas Pharma S.A, Madrid, Spain) to pediatric patients with stable liver or
      kidney transplants. Forty-one pharmacokinetic profiles were obtained after
      Prograf((r)) and Advagraf((r)) administration. LSSs predicting AUC0-24 were
      developed by linear regression using three extraction time points. Selection of
      the most accurate LSS was made based on the r(2) , mean error, and mean absolute
      error. All selected LSSs had higher correlation with AUC0-24 than the correlation
      found between C0 and AUC0-24 . Best LSS for Prograf((r)) in liver transplants was
      C0_1.5_4 (r(2)  = 0.939) and for kidney transplants C0_1_3 (r(2)  = 0.925). For
      Advagraf((r)) , the best LSS in liver transplants was C0_1_2.5 (r(2)  = 0.938)
      and for kidney transplants was C0_0.5_4 (r(2)  = 0.931). Excluding transplant
      type variable, the best LSS for Prograf((r)) is C0-1-3 (r(2)  = 0.920) and the
      best LSS for Advagraf((r)) was C0_0.5_4 (r(2)  = 0.926). Considering transplant
      type irrespective of the formulation used, the best LSS for liver transplants was
      C0_2_3 (r(2)  = 0.913) and for kidney transplants was C0_0.5_4 (r(2)  = 0.898).
      Best LSS, considering all data together, was C0_1_4 (r(2)  = 0.898). We developed
      several LSSs to predict AUC0-24 for tacrolimus in children and adolescents with
      kidney or liver transplants after Prograf((r)) and/or Advagraf((r)) treatment. 

PMID- 24861355
TI  - Current clinical indications for magnetic resonance imaging of the breast.
AB  - MRI is increasingly used in breast cancer patients. MRI has a high sensitivity
      compared to mammography and ultrasound. The specificity is moderate leading to an
      increased risk of false positive findings. Currently, a beneficial effect of
      breast MRI has been established in some patient groups and is debated in the
      general breast cancer population. The diagnostic ability of MRI and its role in
      various groups of breast cancer patients are discussed in this review.

PMID- 24861354
TI  - Current status of prenatal diagnosis in Cuba: causes of low prevalence of Down
      syndrome.
AB  - OBJECTIVES: To analyze trends in cytogenetic prenatal diagnosis in Cuba and to
      analyze possible causes leading to a low Down syndrome prevalence in a country
      where the triple test is not available. METHODS: An analysis of the Cuban program
      in prenatal cytogenetic diagnosis from 1984 to 2012 was conducted. Results are
      described, with particular emphasis on indications, abnormal results, types of
      invasive procedures, and terminations of pregnancy. RESULTS: Cytogenetic prenatal
      diagnostic analyses (n = 75,095) were conducted; maternal age was the indication
      for 77.9% of the amniocenteses and chorionic villus samplings. The detection rate
      of chromosomally abnormal pregnancies was 2.3% for maternal age and increased to
      8-9% for other indications. When a chromosomal abnormality was identified, 88.5%
      terminated the pregnancy. In 2002, the live birth prevalence of Down syndrome was
      8.4 per 10,000 live births, and in 2012, 7 per 10,000. CONCLUSION: Prenatal
      diagnosis in Cuba has contributed to a significant reduction in chromosomal
      aberrations. The impact increased because of the demographic trends of the
      population, the high index of terminations of pregnancy, and the establishment of
      a network of cytogenetic laboratories throughout Cuba.

PMID- 24861356
TI  - Construction and DNA condensation of cyclodextrin-coated gold nanoparticles with
      anthryl grafts.
AB  - The condensation of DNA in a controlled manner is one of the key steps in gene
      delivery and gene therapy. For this purpose, a water-soluble supramolecular
      nanostructure is constructed by coating 14 beta-cyclodextrins onto the surface of
      a gold nanoparticle, followed by the noncovalent association of different amounts
      of anthryl-modified adamantanes with coated beta-cyclodextrins. The strong
      binding of beta-cyclodextrins with anthryl adamantanes (K(S) =8.61*10(4)  M(-1))
      efficiently stabilizes the supramolecular nanostructure. Spectrophotometric
      fluorescence spectra and microscopic studies demonstrated that, with many anthryl
      grafts that can intercalate in the outer space of the DNA double helix, this
      supramolecular nanostructure showed good condensation abilities to calf thymus
      DNA. Significantly, the condensation efficiency of supramolecular nanostructure
      towards DNA could be conveniently controlled by adjusting the ratio between gold
      nanoparticles and anthryl adamantane grafts, leading to the formation of DNA
      condensates of a size that are suitable for the endocytosis of hepatoma cells,
      which will make it potentially applicable in many fields of medicinal science and
      biotechnology.

PMID- 24861357
TI  - A general strategy for site-directed enzyme immobilization by using NiO
      nanoparticle decorated mesoporous silica.
AB  - Mesoporous materials have recently gained much attention owing to their large
      surface area, narrow pore size distribution, and superior pore structure. These
      materials have been demonstrated as excellent solid supports for immobilization
      of a variety of proteins and enzymes for their potential applications as
      biocatalysts in the chemical and pharmaceutical industries. However, the lack of
      efficient and reproducible methods for immobilization has limited the activity
      and recyclability of these biocatalysts. Furthermore, the biocatalysts are
      usually not robust owing to their rapid denaturation in bulk solvents. To solve
      these problems, we designed a novel hybrid material system, mesoporous silica
      immobilized with NiO nanoparticles (SBA-NiO), wherein enzyme immobilization is
      directed to specific sites on the pore surface of the material. This yielded the
      biocatalytic species with higher activity than free enzyme in solution. These
      biocatalytic species are recyclable with minimal loss of activity after several
      cycles, demonstrating an advantage over free enzymes. 

PMID- 24861358
TI  - Comparing treatment goals for psoriasis with treatment decisions in daily
      practice: results from a prospective cohort of patients with psoriasis treated
      with biologics: BioCAPTURE.
AB  - BACKGROUND: Treatment goals have been developed to optimize daily clinical
      practice psoriasis care, but have not yet been studied in real life. OBJECTIVES:
      To investigate to what extent treatment decisions made by dermatologists in daily
      clinical practice for patients with psoriasis on biologics are already in
      accordance with treatment goals without the active application of the treatment
      goals algorithm. METHODS: Data were extracted from a prospective daily practice
      cohort of patients with psoriasis on biologics. Analysis was done on
      effectiveness (Psoriasis Area and Severity Index score) and quality of life
      (Dermatology Life Quality Index questionnaire). Treatment decisions such as
      dosage adjustments, combination treatments, or switching therapy were compared
      with the treatment goals algorithm. RESULTS: In 64% (253 of 395) of visits,
      physicians followed the treatment goals algorithm. There were 162 (41%) visits in
      which there should have been a treatment modification according to treatment
      goals (group Modify) and a modification was indeed made in 59 of these 162 visits
      (36%). In 233 (59%) visits no treatment modification was necessary (group
      Continue) and therapy was indeed not modified in 194 of 233 visits (83%).
      CONCLUSIONS: Physicians acted in accordance with treatment goals in the majority
      of patient visits. In the patient group not achieving these goals, physicians
      should have modified therapy according to treatment goals but continued the same
      therapeutic regimen in the majority of visits. Optimizing therapy and defining
      barriers in the latter group might increase treatment results in daily practice
      psoriasis care.

PMID- 24861359
TI  - Assessment of the genotoxicity and cytotoxicity in environmentally exposed human
      populations to heavy metals using the cytokinesis-block micronucleus cytome
      assay.
AB  - The cytokinesis-block micronucleus cytome (CBMN-Cyt) assay was developed as a
      system for evaluating DNA damage, cytostasis, and cytotoxicity. The aim of the
      present study was to estimate levels of micronuclei (MNi), nucleoplasmic bridges
      (NPBs), nuclear buds (NBUDs), cell death (apoptosis/necrosis), nuclear division
      index, and nuclear division cytotoxicity index values in the peripheral blood
      lymphocytes of environmentally exposed subjects to heavy metals from five Bosnian
      regions, characterized by different exposure to heavy metals. The study was
      performed using CBMN-Cyt assay, considering factors, such as age, gender and
      smoking habits and their possible effects on analyzed parameters. In total, 104
      healthy subjects were selected (49.04% females and 50.96% males; average age,
      35.41 years; 51.92% smokers and 48.08% nonsmokers). There was significant
      difference between the frequency of NBUDs in Tuzla as compared to the control
      group. Furthermore, there was observed a statistically significant difference for
      the frequency of NPBs between Zenica, Olovo, and Kakanj when compared with the
      controls. Males showed a significantly higher number of apoptotic cells than
      females in controls. There were significant differences between smokers and
      nonsmokers in the frequency of NPBs in controls (higher in nonsmokers) and
      necrotic cells in Olovo (higher in nonsmokers). The pack years of smoking
      significantly influenced the number of necrotic cells in controls and the
      frequency of NBUDs in the overall sample. The results of the present study
      provide evidence of significantly increased frequency of NPBs and NBUDs in
      exposed subjects, suggesting that these endpoints are highly sensitive markers
      for measuring genotoxicity.

PMID- 24861360
TI  - Photon-in/photon-out spectroscopic techniques for materials analysis: some recent
      developments.
AB  - Third-generation synchrotron light source technology has greatly improved the
      capabilities for materials analysis using tunable X-rays. Two such capabilities
      developed recently are reported herein - inverse partial fluorescence yield
      (IPFY) XANES (X-ray absorption near edge structure) and 2D XANES - XEOL (X-ray
      excited optical luminescence) in both the energy and time domain. These
      techniques take advantage of recent advances in soft X-ray solid state detector,
      optical spectrometer with a CCD detector and optical streak camera on a soft X
      ray beamline as well as new data acquisition schemes. The studies of LiFePO4
      materials for Li ion battery and solid solutions of GaN-ZnO nanostructures for
      water splitting are used to illustrate these capabilities. The prospects of these
      and related synchrotron photon-in photon-out techniques are also noted. 

PMID- 24861361
TI  - Evaluation of HBV DNA decay kinetics in patients containing both rtM204V/I mutant
      and wild-type HBV subpopulations during tenofovir DF (TDF) monotherapy or
      combination therapy with emtricitabine (FTC)/TDF.
AB  - Tenofovir disoproxil fumarate (TDF) is recommended as treatment for chronic
      hepatitis B patients harboring lamivudine-associated resistance mutations (LAM-R,
      rtM204V/I +/- rtL180M). This study evaluated the clinical response of rtM204V and
      rtM204I subpopulations to TDF by comparing their early viral load decay kinetics
      to wild-type (WT) subpopulations in chronic hepatitis B patients harboring
      rtM204V/I prior to initiating TDF or emtricitabine (FTC)/TDF therapy. Allele
      specific PCR assays capable of detecting rtM204V or rtM204I subpopulations as low
      as 0.5% were developed and used to assess patient samples from a Phase 3b study
      evaluating TDF and FTC/TDF treatment in LAM-R patients. Baseline samples (n =
      280) were quantified for rtM204V/I subpopulations and rtM204V or rtM204I
      subpopulations were detected in 269/273 (98.5%) baseline samples with a range of
      0.7% to >95%. On-treatment analyses were conducted for seventeen patients (TDF, n
      = 8; FTC/TDF, n = 9) that harbored baseline WT and either rtM204V or rtM204I (no
      rtM204V/I mixtures) and HBV DNA >=1,000 copies/ml at/after week 4. The median
      change in HBV DNA through week 12 for WT and rtM204V/I subpopulations was
      similar, -2.64 and -3.30 log10  copies/ml, respectively, with no significant
      difference between TDF and FTC/TDF treatment. In conclusion, rtM204V/I
      subpopulations demonstrate similar early HBV DNA decline kinetics to WT
      subpopulations during treatment with either TDF or FTC/TDF. These results
      demonstrate that TDF is similarly active against both WT and rtM204V/I
      subpopulations in vivo.

PMID- 24861362
TI  - Biomimetic synthesis of shaped and chiral silica entities templated by organic
      objective materials.
AB  - Organic molecules with accompanying self-organization have been a great subject
      in chemistry, material science and nanotechnology in the past two decades. One of
      the most important roles of organized organic molecules is the capability of
      templating complexly structured inorganic materials. The focus of this Minireview
      is on nanostructured silica with divergent morphologies and/or integrated
      chirality directed by organic templates of self-assembled
      polyamine/polypeptides/block copolymers, chiral organogels, self-organized chiral
      amphiphiles and chiral crystalline complexes, etc., by biomimetic silicification
      and conventional sol-gel reaction. Among them, biosilica (diatoms and sponges)
      inspired biomimetic silicifications are particularly highlighted. 

PMID- 24861363
TI  - Microscopic characters of the leaf and stem of Lavandula dentata L. (Lamiaceae).
AB  - Lavandula dentata L. is an aromatic plant used in folk medicine for different
      purposes and, for this reason, phytochemical surveys have been carried out in the
      search for bioactive substances aiming to support its uses. Since there is little
      knowledge on the structural aspects of L. dentata, this work has studied the
      anatomical characters of the leaf and stem using light and scanning electron
      microscopy, in order to assist the species identification. As a result, there are
      different types of trichomes: capitate glandular with uni- or bicellular head,
      peltate glandular with multicellular head, and branched non-glandular. The leaf
      is hypostomatic showing diacytic stomata. The epidermis is uniseriate and coated
      with striate cuticle. The mesophyll is dorsiventral and the midrib is concave
      convex and traversed by a single collateral vascular bundle. The stem is
      quadrangular and has alternating strands of collenchyma and cortical parenchyma
      as well as a typical endodermis in the cortex. The phloem and xylem cylinders are
      traversed by narrow rays and there is an incomplete sclerenchymatic sheath
      adjoining the phloem. These results are a novelty for the species and contribute
      to distinguish it from other lavenders.

PMID- 24861364
TI  - Total synthesis of jiadifenolide.
AB  - As a potent neurotrophic agent, the sesquiterpenoid jiadifenolide represents a
      valuable small-molecule lead for the potential therapeutic treatment of
      neurodegenerative diseases. A stereocontrolled total synthesis of this densely
      functionalized natural product is reported, central to which is an adventurous
      samarium-mediated cyclization reaction to establish the tricyclic core and the
      adjacent C5 and C6 quaternary stereocenters. 

PMID- 24861365
TI  - Interpnictogen cations: exploring new vistas in coordination chemistry.
AB  - Pnictine derivatives can behave as both 2e(-) donors (Lewis bases) and 2e(-)
      acceptors (Lewis acids). As prototypical ligands in the coordination chemistry of
      transition metals, amines and phosphines also form complexes with p-block Lewis
      acids, including a variety of pnictogen-centered acceptors. The inherent Lewis
      acidity of pnictogen centers can be enhanced by the introduction of a cationic
      charge, and this feature has been exploited in recent years in the development of
      compounds resulting from coordinate Pn-Pn and Pn-Pn' interactions. These
      compounds offer the unusual opportunity for homoatomic coordinate bonding and the
      development of complexes that possess a lone pair of electrons at the acceptor
      center. This Review presents new directions in the systematic extension of
      coordination chemistry from the transition series into the p-block. 

PMID- 24861366
TI  - Trait-based diet selection: prey behaviour and morphology predict vulnerability
      to predation in reef fish communities.
AB  - Understanding how predators select their prey can provide important insights into
      community structure and dynamics. However, the suite of prey species available to
      a predator is often spatially and temporally variable. As a result, species
      specific selectivity data are of limited use for predicting novel predator-prey
      interactions because they are assemblage specific. We present a method for
      predicting diet selection that is applicable across prey assemblages, based on
      identifying general morphological and behavioural traits of prey that confer
      vulnerability to predation independent of species identity. We apply this trait
      based approach to examining prey selection by Indo-Pacific lionfish (Pterois
      volitans and Pterois miles), invasive predators that prey upon species-rich reef
      fish communities and are rapidly spreading across the western Atlantic. We first
      generate hypotheses about morphological and behavioural traits recurring across
      fish species that could facilitate or deter predation by lionfish. Constructing
      generalized linear mixed-effects models that account for relatedness among prey
      taxa, we test whether these traits predict patterns of diet selection by lionfish
      within two independent data sets collected at different spatial scales: (i) in
      situ visual observations of prey consumption and availability for individual
      lionfish and (ii) comparisons of prey abundance in lionfish stomach contents to
      availability on invaded reefs at large. Both analyses reveal that a number of
      traits predicted to affect vulnerability to predation, including body size, body
      shape, position in the water column and aggregation behaviour, are important
      determinants of diet selection by lionfish. Small, shallow-bodied, solitary
      fishes found resting on or just above reefs are the most vulnerable. Fishes that
      exhibit parasite cleaning behaviour experience a significantly lower risk of
      predation than non-cleaning fishes, and fishes that are nocturnally active are at
      significantly greater risk. Together, vulnerable traits heighten the risk of
      predation by a factor of nearly 200. Our study reveals that a trait-based
      approach yields insights into predator-prey interactions that are robust across
      prey assemblages. Importantly, in situ observations of selection yield similar
      results to broadscale comparisons of prey use and availability, which are more
      typically gathered for predator species. A trait-based approach could therefore
      be of use across predator species and ecosystems to predict the outcomes of
      changing predator-prey interactions on community dynamics. 

PMID- 24861367
TI  - Safety Assessment of Citric Acid, Inorganic Citrate Salts, and Alkyl Citrate
      Esters as Used in Cosmetics.
AB  - The CIR Expert Panel (Panel) assessed the safety of citric acid, 12 inorganic
      citrate salts, and 20 alkyl citrate esters as used in cosmetics, concluding that
      these ingredients are safe in the present practices of use and concentration.
      Citric acid is reported to function as a pH adjuster, chelating agent, or
      fragrance ingredient. Some of the salts are also reported to function as
      chelating agents, and a number of the citrates are reported to function as skin
      conditioning agents but other functions are also reported. The Panel reviewed
      available animal and clinical data, but because citric acid, calcium citrate,
      ferric citrate, manganese citrate, potassium citrate, sodium citrate, diammonium
      citrate, isopropyl citrate, stearyl citrate, and triethyl citrate are generally
      recognized as safe direct food additives, dermal exposure was the focus for these
      ingredients in this cosmetic ingredient safety assessment.

PMID- 24861368
TI  - Safety Assessment of Cucumis sativus (Cucumber)-Derived Ingredients as Used in
      Cosmetics.
AB  - The CIR Expert Panel assessed the safety of 6 Cucumis sativus (cucumber)-derived
      ingredients and found them safe in cosmetic formulations in the present practices
      of use and concentration. These ingredients are reported to function in cosmetics
      as skin-conditioning agents. Cucumber is a commonly consumed food with no history
      of significant adverse effects, suggesting that its ingredients should not pose
      any major safety issues following oral exposure. This assessment focused on the
      dermal exposure to the low concentrations of these ingredients as used in
      cosmetics. Some of the constituents of cucumbers have been assessed previously
      for safe use as cosmetic ingredients.

PMID- 24861369
TI  - Safety Assessment of Chlorphenesin as Used in Cosmetics.
AB  - Chlorphenesin functions as a biocide in cosmetics and is used at concentrations
      up to 0.32% in rinse-off products and up to 0.3% in leave-on products. The
      Cosmetic Ingredient Review Expert Panel (Panel) noted that chlorphenesin was well
      absorbed when applied to the skin of rats; however, any safety concern was
      minimized because available data demonstrated an absence of toxicity. The Panel
      concluded that chlorphenesin is safe in the present practices of use and
      concentration.

PMID- 24861370
TI  - Safety Assessment of Dimethicone Crosspolymers as Used in Cosmetics.
AB  - The Cosmetic Ingredient Review Expert Panel (Panel) reviewed the safety of 62
      dimethicone crosspolymer ingredients as used in cosmetics. These ingredients
      function mostly as absorbents, bulking agents, film formers, hair-conditioning
      agents, emollient skin-conditioning agents, slip modifiers, surface modifiers,
      and nonaqueous viscosity-increasing agents. The Panel reviewed available animal
      and human data related to these polymers and addressed the issue of residual
      monomers. The Panel concluded that these dimethicone crosspolymer ingredients are
      safe in the practices of use and concentration as given in this safety
      assessment.

PMID- 24861373
TI  - Construction of stable chainlike Au nanostructures via silica coating and
      exploration for potential photothermal therapy.
AB  - A facile one-pot approach is successfully developed to construct the stable Au
      nanochains with silica shell via self-assembly and classical Stober process. The
      resulting Au chain@SiO2 nanoparticles holds great promise for serving as a safe,
      reusable, and high-performance photothermal agent against cancer. 

PMID- 24861371
TI  - Tumor signatures of PTHLH overexpression, high serum calcium, and poor prognosis
      were observed exclusively in clear cell but not non clear cell renal carcinomas.
AB  - High serum calcium (Ca) due to aberrant secretion of tumor parathyroid hormone
      like hormone (PTHLH) is a well-known paraneoplastic sign and is associated with
      poor prognosis in patients with renal cell carcinoma (RCC). However, the status
      of serum Ca and tumor PTHLH expression have not been verified using the 2004
      World Health Organization (WHO) renal tumor classification. We retrospectively
      reviewed corrected serum Ca levels at initial onset (n = 683) and/or as of
      recurrence (n = 71) in patients with RCC. We also examined a total of 623 renal
      parenchymal tumor samples for PTHLH mRNA expressions by quantitative real-time
      PCR. High serum Ca concomitant with PTHLH overexpression in tumors was observed
      exclusively in clear cell RCC but not in other non clear cell subtype tumors,
      including papillary, chromophobe, collecting-duct, unclassified, and other rare
      subtype RCCs or in benign oncocytomas and angiomyolipomas. In clear cell RCC,
      PTHLH expression was significantly high in male patients, and was associated with
      a symptomatic presentation, higher grade, and higher stage cases, whereas it was
      not associated with VHL gene status. Univariate analyses demonstrated that high
      PTHLH expression was strongly associated with poor outcome both in overall
      survival (OS) and disease-free survival (DFS) for patients who underwent standard
      nephrectomy. Further multivariate Cox analyses revealed that the PTHLH
      expressions remained as independent prognostic parameters for OS but not for DFS.
      These data suggest that the previously characterized tumor signatures of high
      serum Ca due to high PTHLH expression and poor prognosis are clear cell RCC
      specific features, whereas these characteristics are rare in non clear cell RCCs.

PMID- 24861374
TI  - Plasmodium knowlesi: clinical presentation and laboratory diagnosis of the first
      human case in a Scottish traveler.
AB  - The first imported case of Plasmodium knowlesi in Scotland is described in a 33
      year-old female with a travel history to Borneo. The patient ceased to take
      antimalarial prophylaxis after 4 days of her 10-day visit and presented with a
      history of fever, rigor, vomiting, and diarrhea after 13 days on her return to
      the UK. Malaria antigen detection using the Optimal-IT and Binax-NOW kits was
      negative. Unusual trophozoite-like structures were observed under microscopic
      examination and the identification of P. knowlesi performed by a nested
      polymerase chain reaction (PCR) gel-based approach was confirmed by using a PCR
      sequencing assay.

PMID- 24861375
TI  - A new high phenyl lactic acid-yielding Lactobacillus plantarum IMAU10124 and a
      comparative analysis of lactate dehydrogenase gene.
AB  - Phenyl lactic acid (PLA) has been widely reported as a new natural antimicrobial
      compound. In this study, 120 Lactobacillus plantarum strains were demonstrated to
      produce PLA using high-performance liquid chromatography. Lactobacillus plantarum
      IMAU10124 was screened with a PLA yield of 0.229 g L(-1) . Compared with all
      previous reports, this is the highest PLA-producing lactic acid bacteria (LAB)
      when grown in MRS broth without any optimizing conditions. When 3.0 g L(-1)
      phenyl pyruvic acid (PPA) was added to the medium as substrate, PLA production
      reached 2.90 g L(-1) , with the highest 96.05% conversion rate. A lowest PLA
      yielding L. plantarum IMAU40105 (0.043 g L(-1) ) was also screened. It was shown
      that the conversion from PPA to PLA by lactic dehydrogenase (LDH) is the key
      factor in the improvement of PLA production by LAB. Comparing the LDH gene of two
      strains, four amino acid mutation sites were found in this study in the LDH of L.
      plantarum IMAU10124.

PMID- 24861376
TI  - Psychological interventions for acute pain after open heart surgery.
AB  - BACKGROUND: Acute postoperative pain is one of the most disturbing complaints in
      open heart surgery, and is associated with a risk of negative consequences.
      Several trials investigated the effects of psychological interventions to reduce
      acute postoperative pain and improve the course of physical and psychological
      recovery of participants undergoing open heart surgery. OBJECTIVES: To compare
      the efficacy of psychological interventions as an adjunct to standard care versus
      standard care alone or standard care plus attention in adults undergoing open
      heart surgery on pain, pain medication, mental distress, mobility, and time to
      extubation. SEARCH METHODS: We searched the Cochrane Central Register of
      Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 8), MEDLINE (1946
      to September 2013), EMBASE (1980 to September 2013), Web of Science (all years to
      September 2013), and PsycINFO (all years to September 2013) for eligible studies.
      We used the 'related articles' and 'cited by' options of eligible studies to
      identify additional relevant studies. We also checked lists of references of
      relevant articles and previous reviews. We also searched the ProQuest
      Dissertations and Theses Full Text Database (all years to September 2013) and
      contacted the authors of primary studies to identify any unpublished material.
      SELECTION CRITERIA: Randomised controlled trials comparing psychological
      interventions as an adjunct to standard care versus standard care alone or
      standard care plus attention in adults undergoing open heart surgery. DATA
      COLLECTION AND ANALYSIS: Two review authors (SK and JR) independently assessed
      trials for eligibility, estimated the risk of bias and extracted all data. We
      calculated effect sizes for each comparison (Hedges' g) and meta-analysed data
      using a random-effects model. MAIN RESULTS: Nineteen trials were included (2164
      participants).No study reported data on the number of participants with pain
      intensity reduction of at least 50% from baseline. Only one study reported data
      on the number of participants below 30/100 mm on the Visual Analogue Scale (VAS)
      in pain intensity. Psychological interventions have no beneficial effects in
      reducing pain intensity measured with continuous scales in the medium-term
      interval (g -0.02, 95% CI -0.24 to 0.20, 4 studies, 413 participants, moderate
      quality evidence) nor in the long-term interval (g 0.12, 95% CI -0.09 to 0.33, 3
      studies, 280 participants, low quality evidence).No study reported data on median
      time to remedication or on number of participants remedicated. Only one study
      provided data on postoperative analgesic use. Studies reporting data on mental
      distress in the medium-term interval revealed a small beneficial effect of
      psychological interventions (g 0.36, 95% CI 0.10 to 0.62, 12 studies, 1144
      participants, low quality evidence). Likewise, a small beneficial effect of
      psychological interventions on mental distress was obtained in the long-term
      interval (g 0.28, 95% CI 0.05 to 0.51, 11 studies, 1320 participants, low quality
      evidence). There were no beneficial effects of psychological interventions on
      mobility in the medium-term interval (g 0.23, 95% CI -0.22 to 0.67, 3 studies,
      444 participants, low quality evidence) nor in the long-term interval (g 0.29,
      95% CI -0.14 to 0.71, 4 studies, 423 participants, low quality evidence). Only
      one study reported data on time to extubation. AUTHORS' CONCLUSIONS: For the
      majority of outcomes (two-thirds) we could not perform a meta-analysis since
      outcomes were not measured, or data were provided by one trial only.
      Psychological interventions have no beneficial effects on reducing postoperative
      pain intensity or enhancing mobility. There is low quality evidence that
      psychological interventions reduce postoperative mental distress. Due to
      limitations in methodological quality, a small number of studies, and large
      heterogeneity, we rated the quality of the body of evidence as low. Future trials
      should measure crucial outcomes (e.g. number of participants with pain intensity
      reduction of at least 50% from baseline) and should focus to enhance the quality
      of the body of evidence in general. Altogether, the current evidence does not
      clearly support the use of psychological interventions to reduce pain in
      participants undergoing open heart surgery.

PMID- 24861377
TI  - Gene polymorphism and frequencies of the NPC1L1 gene (rs2072183, rs217434 and
      rs217428) in Japanese patients with dyslipidemia.
AB  - WHAT IS KNOWN AND OBJECTIVE: Niemann-Pick C1-Like 1 (NPC1L1) plays a pivotal role
      in intestinal cholesterol absorption. Ezetimibe is known as an inhibitor for
      NPC1L1 and decreases concentration of low-density lipoprotein cholesterol (LDL-C)
      in blood. Responses of the decrease of serum LDL-C levels to ezetimibe have been
      reported to be different among NPC1L1 variants. However, there are still limited
      data concerning the genetic variation in the NPC1L1 gene, specifically, in
      Japanese patients with dyslipidemia. The purpose of this study is to elucidate
      genotype and allele frequencies of the NPC1L1 gene in Japanese patients with
      dyslipidemia. METHODS: Written informed consent was obtained from all
      participants. All patients were administered ezetimibe at the dose of 10 mg for
      once a day either alone or coadministered with statins. Patient's data were
      retrospectively obtained from their medical records. Genomic DNA was extracted
      from whole blood samples and analysed three NPC1L1 SNPs (rs2072183, rs217428 and
      rs217434) by the direct sequencing method. RESULTS AND DISCUSSION: We found that
      there is a significant difference of genotype frequencies between healthy
      Japanese and dyslipidemic subjects in rs2072183. No significant differences were
      observed in rs217428 and rs217434; however, comparison of our data with
      literature reports suggests that there are significant differences in the
      frequencies of rs217428 and rs217434 between Canadian and Japanese dyslipidemic
      patients. WHAT IS NEW AND CONCLUSION: Our study is the first report concerning
      the genotype and allele frequencies of the gene coding for NPC1L1 in Japanese
      patients with dyslipidemia. The most notable result was to demonstrate that there
      exists a significant difference in rs2072183 variant between healthy Japanese and
      dyslipidemic subjects and also found that there exists genetic variation of
      rs2072183 between Japanese and Canadian patients with dyslipidemia. Our results
      are expected to facilitate research in the proper use of ezetimibe-based mono- or
      combination therapies. Further studies will be required to evaluate the effects
      of rs2072183 on the efficacy of LDL cholesterol reduction by ezetimibe.

PMID- 24861378
TI  - Anatomic findings and complications after surgical treatment of chronic, partial
      distal biceps tendon tears: a case cohort comparison study.
AB  - PURPOSE: To describe pertinent anatomic findings during repair of chronic,
      partial distal biceps tendon tears and to compare the complications of surgery
      with a similar cohort of acute, complete tears. METHODS: Group 1 included 14
      patients (15 elbows) with partial tears managed operatively an average of 10
      months from onset of injury or symptoms. Group 2 included a matched cohort of 16
      patients (17 elbows) treated for complete, acute tears an average of 19 days from
      injury. A retrospective review of all 30 patients focused on demographic data,
      intraoperative findings, and postoperative complications. A single, anterior
      incision was used in all cases with multiple suture anchors or a bicortical
      toggling button for fixation of the repair. RESULTS: We evaluated 27 men and 3
      women with an average age of 55 years (group 1) and 48 years (group 2).
      Intratendinous ganglion formation at the site of rupture of the degenerative
      tendon was observed in 5 cases of partial tears and none of the complete tears.
      Partial tears involved the lateral aspect or short head of the biceps tendon
      insertion in all cases. Postoperative complications included lateral antebrachial
      cutaneous nerve neuritis in 8 group 1 patients and 6 group 2 patients and
      transient posterior interosseus nerve palsy in 3 group 1 patients. CONCLUSIONS:
      Partial distal biceps tendon ruptures showed a consistent pattern of pathology
      involving disruption of the lateral side of the tendon insertion involving the
      small head of the biceps. Degenerative intratendinous ganglion formation was
      present in one third of cases. Repair of chronic, partial distal biceps tendon
      injuries may have a higher incidence of posterior interosseous and lateral
      antebrachial cutaneous nerve palsies. TYPE OF STUDY/LEVEL OF EVIDENCE:
      Therapeutic III.

PMID- 24861379
TI  - The effect of pisiform excision on wrist function.
AB  - PURPOSE: To investigate the effect of pisiform excision on wrist function
      compared with age- and sex-matched control subjects. METHODS: The authors
      evaluated the charts of 11 consecutive patients who had undergone pisiform
      excision. Nine of these patients could be included and clinically examined, and
      results were compared with 9 matched controls. Measurements included range of
      motion, strength measurements, neurological examination, and questionnaires.
      RESULTS: Extension in the operated wrist was reduced in patients compared with
      controls. The Disabilities of the Arm, Shoulder, and Hand and Michigan Hand
      Outcomes Questionnaires were significantly different between patients and
      controls. All other entities were equal between groups. Subjectively, patients
      experienced impairments in function of the operated wrist, but these could not be
      identified objectively. CONCLUSIONS: Although great care must be taken in
      handling the surrounding soft tissue, pisiform excision is a well-tolerated, safe
      treatment for pain in the pisotriquetral joint resulting from arthrosis and not
      controlled by nonsurgical means. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic
      III.

PMID- 24861380
TI  - Medial collateral ligament of the elbow: acute deterioration in throwing
      athletes.

PMID- 24861381
TI  - Simultaneous proximal interphalangeal joint arthroplasty and extensor tendon
      reconstruction in adjacent fingers: case report.
AB  - We present a case of a young man with heavily injured proximal interphalangeal
      joints and deficits of the extensor mechanism in 2 fingers treated by silicone
      proximal interphalangeal joint arthroplasty and 2-stage reconstruction of the
      extensor mechanism. The postoperative result was satisfactory with a painless, if
      limited, active arc of motion of the proximal interphalangeal joints of 50
      degrees  in the middle finger and 35 degrees  in the ring finger. 

PMID- 24861382
TI  - Patient activation and disability in upper extremity illness.
AB  - PURPOSE: To determine if higher patient activation (active involvement in one's
      health care) correlates with fewer symptoms and less disability in patients with
      hand and upper extremity illness. METHODS: We enrolled 112 patients presenting to
      our department for the first time. Before meeting with the surgeon, subjects
      completed a demographics questionnaire, the short form Patient Activation
      Measure; Quick Disabilities of the Arm, Shoulder, and Hand; Patient Health
      Questionnaire-2; Pain Self-Efficacy Questionnaire; and an 11-point ordinal rating
      of pain intensity. We contacted patients 1 to 2 months after enrollment. Seventy
      five subjects completed the second evaluation over the telephone, on a secure
      data-collection web site, or in an office visit, which included the Patient
      Activation Measure; Quick Disabilities of the Arm, Shoulder, and Hand; numerical
      rating scale for pain; and ordinal rating of treatment satisfaction. RESULTS:
      Patient activation at enrollment correlated with disability, pain intensity, and
      satisfaction with treatment but was only retained in the multivariable model for
      pain intensity. Pain self-efficacy at enrollment was the factor that best
      accounted for variation in disability, pain, and satisfaction with treatment.
      CONCLUSIONS: Given the consistent relationship between effective coping
      strategies (eg, pain self-efficacy) and symptoms and disability and the
      independent influence of patient activation on pain intensity in this study,
      future research should address the ability of interventions that improve self
      efficacy and patient activation to improve upper extremity health. TYPE OF
      STUDY/LEVEL OF EVIDENCE: Prognostic II.

PMID- 24861383
TI  - Necrotizing fasciitis.

PMID- 24861384
TI  - Long-term results of arthroscopic wrist synovectomy in rheumatoid arthritis.
AB  - PURPOSE: To investigate the effects of arthroscopic wrist synovectomy on the
      clinical course of rheumatoid arthritis in a large series with long-term follow
      up. METHODS: We performed arthroscopic synovectomy on 56 wrists in 49 patients
      with rheumatoid arthritis. At a mean follow-up of 7.9 years (range, 5-12 y), we
      evaluated pain and patient satisfaction using a visual analog scale and assessed
      overall function using the Mayo wrist score. Radiographic stage was graded
      according to Larsen stage. We determined clinical outcomes on the recurrence of
      wrist synovitis, which we evaluated by symptoms of pain and swelling and physical
      examination. Preoperative variables were statistically analyzed to find factors
      that could influence the results. RESULTS: The mean visual analog scale score for
      wrist pain decreased from 6.3 to 1.7, and the mean Mayo wrist score (evaluated in
      39 wrists) improved from 48 (range, 5-70) to 76 (range, 55-100). The mean visual
      analog scale score for patient satisfaction was 7.9. At final follow-up,
      synovitis was controlled in 42 wrists (75%) and recurred in the others. The mean
      Larsen stage progressed from 2.2 to 3.3. Analysis of preoperative variables
      revealed no factors that significantly affected clinical outcomes in terms of
      sex, age, duration of wrist symptom, preoperative serologic inflammatory markers,
      or Larsen stage. CONCLUSIONS: Arthroscopic synovectomy of the wrist can provide
      pain relief and functional improvement with control of synovitis in 75% of
      rheumatoid wrists that have not responded to medication. TYPE OF STUDY/LEVEL OF
      EVIDENCE: Therapeutic IV.

PMID- 24861385
TI  - Grid topologies for the self-organizing map.
AB  - The original Self-Organizing Feature Map (SOFM) has been extended in many ways to
      suit different goals and application domains. However, the topologies of the map
      lattice that we can found in literature are nearly always square or, more rarely,
      hexagonal. In this paper we study alternative grid topologies, which are derived
      from the geometrical theory of tessellations. Experimental results are presented
      for unsupervised clustering, color image segmentation and classification tasks,
      which show that the differences among the topologies are statistically
      significant in most cases, and that the optimal topology depends on the problem
      at hand. A theoretical interpretation of these results is also developed. 

PMID- 24861386
TI  - Are we maintaining the standard?

PMID- 24861387
TI  - Anaphylaxis: an update for dental practitioners.
AB  - Anaphylaxis is an acutely presenting life-threatening medical emergency. Surveys
      indicate that dentists feel inadequately able to recognize and treat anaphylaxis.
      This paper reviews the terminology and pathophysiology of anaphylaxis, and
      describes the recognition and initial management of anaphylaxis for dentists.
      Dentists should be able to administer intramuscular adrenaline during anaphylaxis
      at the appropriate dose. The role of further medical care is also explained. Six
      cases of anaphylaxis arising from dental oral maxillofacial surgery practice are
      discussed. 

PMID- 24861388
TI  - A study of osseointegrated dental implants following cremation.
AB  - BACKGROUND: The comparison of dental morphology and restorative work for human
      identification has been well documented. This case study involved documentation
      of osseointegrated and clinically restored dental implants following cremation.
      METHODS: The mandible and the maxilla were excised from a head containing
      implants and cremated. The remains were retrieved, digital and radiographic
      images were taken and elemental analysis undertaken. The brand of implants was
      identified utilizing web based search engines. A prosthodontist, known to
      commonly use this implant system, was approached to ascertain possibilities that
      matched the data given. RESULTS: Following cremation the implants were identified
      and a prosthodontist was able to identify the deceased. Two implants in the
      maxilla had dehiscences on their buccal surfaces, which could not be detected by
      periapical radiographs. CONCLUSIONS: Dental implants osseointegrated and restored
      with a prosthetic superstructure were recognizable following severe incineration.
      It was possible to trace back the identity of the unknown victim to a
      prosthodontist. Bone dehiscences discovered in this study highlighted how two
      dimensional radiographs may not reveal lack of bone support.

PMID- 24861389
TI  - Effect on interleukin-1beta and interleukin-8 levels following use of fibrin
      sealant for periodontal surgery.
AB  - BACKGROUND: Fibrin sealant (FS) is a biologically derived tissue adhesive for
      securing flaps. The aim of the present randomized controlled clinical trial was
      to compare early wound healing by assessing interleukin-1beta (IL-1beta) and
      interleukin-8 (IL-8) levels from gingival crevicular fluid (GCF) after using FS
      and suture for periodontal flap closure. METHODS: Thirty selected quadrants in 15
      periodontitis patients were randomly assigned to either a test (fibrining) or
      control group (suturing) for flap closure. IL-1beta and IL-8 were assessed in GCF
      using enzyme-linked immunosorbent assay (ELISA) before and eight days after
      surgery. Patients were recalled at 7, 14, 21 days and 3 months after surgery for
      clinical assessment. RESULTS: There was a statistically significant decrease in
      IL-1beta (84.82 +/- 77.18, 29.2 +/- 21.97 pg/MUl) and IL-8 (57.94 +/- 55.47,
      21.82 +/- 21.93 pg/MUl) levels in the test side after fibrining while there was
      an increase in the control side (IL-1beta 31.40 +/- 16.82, 128.8 +/- 45.14; IL-8
      31.40 +/- 16.82, 128.83 +/- 45.14 pg/MUl) (p < 0.05). The change in concentration
      of IL-1beta and IL-8 following intervention correlated significantly in both the
      sites. Clinical parameters differed significantly only on the seventh day with
      less plaque and bleeding on the test sites. CONCLUSIONS: Fibrin sealant enhances
      early wound healing by reducing inflammation after periodontal flap surgery.

PMID- 24861391
TI  - After hours presentation of traumatic dental injuries to a major paediatric
      teaching hospital.
AB  - BACKGROUND: Thorough record taking of traumatic dental injuries is vital. This
      study aimed to assess the efficacy of a structured paper history for this
      purpose. Furthermore, the aetiology and epidemiology of these injuries were
      investigated, with the aim of formulating appropriate preventive guidelines.
      METHODS: A six-month audit of traumatic dental injuries presenting after hours
      was undertaken at The Children's Hospital at Westmead. A structured paper history
      form was subsequently created, and the data collected over the following 12
      months. RESULTS: Structured paper histories assisted in thorough record taking.
      Over 12 months, 190 paediatric patients (male:female ratio 1.5:1) were treated
      after hours with traumatic dental injuries. There were 396 injured teeth among
      182 patients (eight patients had soft tissue injuries only). The mean number of
      injured teeth per patient with dental injuries was 2.18, the vast majority being
      maxillary central incisors (62% of primary teeth and 66% of permanent teeth). The
      most common cause was 'accident during play', followed by a fall. The severe
      injuries, avulsions and luxations, comprised 63% of injuries to primary teeth and
      26% to permanent teeth. CONCLUSIONS: Structured paper histories are useful for
      recording traumatic dental injuries. The vast majority of these injuries are due
      to unavoidable accidents, rendering their prevention challenging from a public
      health perspective.

PMID- 24861390
TI  - Clinical and microbiological characterization of localized aggressive
      periodontitis: a cohort study.
AB  - BACKGROUND: Localized aggressive periodontitis (LAgP) is an infectious
      periodontal disease which generally affects young people. Recent data suggest the
      involvement of different bacterial species in different populations. The
      causative bacterial species in Israel has never been identified despite a high
      prevalence of LAgP in this population. The objectives of this study were to
      characterize the bacterial microbiota of periodontal pockets within an Israeli
      LAgP population who were also clinically assessed. METHODS: Twenty-one LAgP
      patients (test) and 12 chronic periodontitis patients (control) were examined.
      Bacterial samples were collected from periodontal pockets and analysed by both
      culture and polymerase chain reaction techniques. Mann-Whitney U test and chi
      square test were used to compare results between the groups. RESULTS: Higher
      levels of Parvimonas micra (>10(6) ), Aggregatibacter actinomycetemcomitans
      (>10(5) ), Fusobacterium nucleatum/F. periodonticum (>10(6) ), and Tannerella
      forsythia (levels of 10(5) to 10(6) bacteria) were detected in the LAgP group
      compared to the control (p < 0.05), while levels of Porphyromonas gingivalis and
      Prevotella intermedia were higher in the CP group. CONCLUSIONS: The
      characteristic periodontal bacterial flora of LAgP patients in Israel is mainly
      comprised of P. micra, A. actinomycetemcomitans, F. nucleatum/F. periodonticum
      and T. forsythia. Similar population based studies of each population will
      improve the quality of treatment of LAgP when individual sampling is not
      possible.

PMID- 24861392
TI  - Fluoride content of tank water in Australia.
AB  - BACKGROUND: The aims of this study were to: (1) analyse the fluoride content of
      tank water; (2) determine whether the method of water collection or storage
      influenced fluoride content; and (3) survey participant attitudes towards water
      fluoridation. METHODS: Plastic tubes and a questionnaire were distributed through
      dentists to households with water tanks in Victoria. A midstream tank water
      sample was collected and fluoride analysed in triplicate using ion chromatography
      RESULTS: All samples (n = 123) contained negligible amounts of fluoride, with a
      mean fluoride concentration of <0.01 ppm (range: <0.01-0.18 ppm). No
      statistically significant association was found between fluoride content and
      variables investigated such as tank material, tank age, roof material and gutter
      material. Most people did not know whether their tank water contained fluoride
      and 40.8% preferred to have access to fluoridated water. The majority thought
      fluoride was safe and more than half of the respondents supported fluoridation.
      Fluoride content of tank water was well below the optimal levels for caries
      prevention. CONCLUSIONS: People who rely solely on tank water for drinking may
      require additional exposure to fluoride for optimal caries prevention.

PMID- 24861393
TI  - A decade of experience evolving visiting dental services in partnership with
      rural remote Aboriginal communities.
AB  - BACKGROUND: Embedding research capabilities and workforce development activities
      with clinical service entities promotes the development of sustainable,
      innovative, quality-focused oral health care services. Clinical and strategic
      governance is an important area of consideration for rural and remote dental
      services, posing particular challenges for smaller service structures. Sustaining
      remote area dental services has some significant complexities beyond those
      involved in urban service models. METHODS: This study describes the sustaining
      structure of a remote area dental service with a decade of history. RESULTS: In
      the current climate, chief among these challenges may be those associated with
      dental workforce shortages as these impact most heavily in the public sector, and
      most particularly, in remote areas. As sustained workforce solutions come from
      developing a future workforce, an essential element of the workforce governance
      framework for remote dental service provision should be the inclusion of a
      student participation programme. Collaborative partnership approaches with
      Aboriginal health services promote the development and maintenance of effective,
      culturally sensitive dental services within rural and remote Aboriginal
      communities. Having sustained care for 10 years, this collaborative model of
      integrated research, education and service has demonstrated its effectiveness as
      a service model for Aboriginal communities in Western Australia. CONCLUSIONS:
      This descriptive study finds the core values for this success have been
      communication, clinical leadership, mentorship within effective governance
      systems all linked to an integrated education and research agenda.

PMID- 24861394
TI  - Effect of dentine conditioning on adhesion of resin-modified glass ionomer
      adhesives.
AB  - BACKGROUND: The aim of this study was to investigate the use of phosphoric acid
      as a surface treatment compared to traditional conditioning agents to dentine
      bonded with resin-modified glass ionomer (RMGIC) adhesives. METHODS: Forty human
      molars were utilized in microtensile bond strength testing, while another 16 were
      used for evaluation of the bonded interface with scanning electron microscopy.
      Three RMGIC adhesives were evaluated: Fuji Bond LC (GC Corp); Riva Bond LC (SDI
      Ltd); and Ketac N100 (3M-ESPE). Surface treatments were 37% phosphoric acid (5 s)
      or 25-30% polyacrylic acid (PAA) (10 s), or the manufacturer's method - Fuji Bond
      LC: Cavity Conditioner (20% PAA + 3% AlCl3 10 s) or Ketac N100 primer: Ketac Nano
      priming agent (15 s). Teeth were finished with 600-grit SiC paper, surfaces
      treated and bonded with RMGIC adhesive and stored in distilled water for 24 h
      then subjected to microtensile bond strength testing. RESULTS: Two-way analysis
      of variance (ANOVA) revealed adhesion was affected by the 'type of RMGIC
      adhesive' and 'method of dentine surface treatment' (p < 0.05). The microtensile
      bond strength of Ketac N100 primer groups was lower than Fuji Bond LC and Riva
      Bond LC (p < 0.05). CONCLUSIONS: For RMGIC adhesives a brief etch with phosphoric
      acid does not adversely effect short-term bond strengths, but is no better than
      traditional conditioning with PAA.

PMID- 24861395
TI  - Hard to reach communities or hard to access services? Migrant mothers'
      experiences of dental services.
AB  - BACKGROUND: Good oral health is an important component of overall health which
      can help migrants settle in a new country. Infant oral health is intimately
      associated with maternal oral health knowledge and behaviours and therefore,
      encounters with dental services. This study aimed to explore the experiences of
      dental service use from the perspective of migrant mothers living in Melbourne,
      Australia. METHODS: A participatory research approach utilizing qualitative
      methods was adopted. Women from Iraq, Lebanon and Pakistan participated. Semi
      structured focus groups and interviews were conducted and thematic analysis of
      the data was completed. RESULTS: Focus groups (n = 11) and interviews (n = 7)
      were conducted with 115 women. Despite an understanding that visiting the dentist
      was important for promoting oral health, the first dental contact for both the
      women and their children was typically for emergency care. Accessibility, cost
      and waiting lists were identified as significant barriers to attendance.
      Problematic interpreter encounters often led to negative experiences which were
      compounded by a perception that public services provided poorer quality of care.
      CONCLUSIONS: Despite evidence of poorer oral health, migrant women face
      significant barriers in accessing mainstream dental services. Reorientation of
      such services, to address the accessibility and experience for migrant
      communities may help reduce oral health inequalities.

PMID- 24861396
TI  - Fluoride release, recharge and flexural properties of polymethylmethacrylate
      containing fluoridated glass fillers.
AB  - BACKGROUND: The purpose of this study was to investigate the effect of
      fluoridated glass fillers on fluoride release, recharge and the flexural
      properties of modified polymethylmethacrylate (PMMA). METHODS: Specimens of PMMA
      denture base material with various loading of fluoridated glass fillers (0%, 1%,
      2.5%, 5% and 10% by weight) were prepared. Flexural properties were evaluated on
      rectangular specimens (n = 10) aged in deionized water after 24 hours, 1 and 3
      months. Disc specimens (n = 10) were aged for 43 days in deionized water and
      lactic acid (pH 4.0) and fluoride release was measured at numerous intervals.
      After ageing, specimens were recharged and fluoride re-release was recorded at 1,
      3 and 7 days after recharge. RESULTS: Samples containing 2.5%, 5% and 10% glass
      fillers showed significantly (p < 0.05) greater levels of fluoride release
      compared with the control and 1% glass fillers specimens. All experimental
      specimens exhibited fluoride release in both media. The flexural strength of
      specimens decreased in proportion to the percentage filler inclusion with the
      modulus of elasticity values remaining within ISO Standard 1567. CONCLUSIONS: The
      modified PMMA with fluoridated glass fillers has the ability to release and re
      release fluoride ion. Flexural strength decreased as glass filler uploading
      increased.

PMID- 24861397
TI  - A retrospective analysis of oral and maxillofacial pathology in an Australian
      adult population.
AB  - BACKGROUND: The prevalence of oral and maxillofacial pathology has not previously
      been reported in the Australian adult population. This study aimed to audit a
      large pathology service to provide insight into the prevalence of head and neck
      pathologies. METHODS: Written records of a major Australian oral pathology
      service were imported into an electronic database. Age, gender and histological
      diagnosis were assessed. Prevalence of histological diagnoses as a percentage of
      the major diagnostic categories and of the whole sample were calculated, as well
      as gender predilections and mean age of presentation of disease. RESULTS: A total
      of 6344 oral pathology specimens, collected from adults aged 17 years and over
      were included in the analysis. Mucosal pathology was the most common pathology
      (37.2%), followed by odontogenic cysts (16.3%) and dental pathology (14.5%). The
      three most common histological diagnoses were fibrous hyperplasia (15.2%),
      chronic periapical granuloma (9.6%) and radicular cyst (9.5%). The male:female
      ratio of the entire sample was 0.74. CONCLUSIONS: This is the first study to
      describe the prevalence of oral and maxillofacial pathology among adult patients
      in an Australian population. The trends seen in this study are repeated in
      studies from other parts of the world, and are of diagnostic importance.

PMID- 24861399
TI  - Self-rated oral health and oral health-related factors: the role of social
      inequality.
AB  - BACKGROUND: The reasons why social inequality is associated with oral health
      outcomes is poorly understood. This study investigated whether stratification by
      different measures of socio-economic status (SES) helped elucidate these
      associations. METHODS: Cross-sectional survey data were used from Australia's
      2004-06 National Survey of Adult Oral Health. The outcome variable was poor self
      rated oral health. Explanatory variables comprised five domains: demographic,
      economic, general health behaviour, oral health-related quality of life and
      perceived need for dental care. These explanatory variables were each stratified
      by three measures of SES: education, income and occupation. RESULTS: The overall
      proportion of adults reporting fair or poor oral health was 17.0% (95% CI 16.1,
      18.0). Of these, a higher proportion were older, Indigenous, non-Australian born,
      poorly educated, annual income <$20 000, unemployed, eligible for public dental
      care, smoked tobacco, avoided food in the last 12 months, experienced discomfort
      with their dental appearance, experienced toothache or reported a need for dental
      care. In stratified analyses, a greater number of differences persisted in the
      oral health impairment and perceived need for dental care domains. CONCLUSIONS:
      Irrespective of the SES measure used, more associations between self-rated oral
      health and dental-specific factors were observed than associations between self
      rated oral health and general factors.

PMID- 24861398
TI  - A retrospective analysis of oral and maxillofacial pathology in an Australian
      paediatric population.
AB  - BACKGROUND: The prevalence of oral and maxillofacial pathology has not previously
      been reported in the Australian paediatric population. This study aimed to audit
      a large pathology service to provide insight into the prevalence of oral and
      maxillofacial pathology. METHODS: Written records of a major Australian oral
      pathology service were imported into an electronic database. Age, gender and
      histological diagnosis were assessed. Prevalence of histological diagnoses as a
      percentage of the major diagnostic categories and of the whole sample were
      calculated, as well as gender predilections and mean age of presentation of
      disease. RESULTS: A total of 1305 oral pathology specimens, collected from
      paediatric patients aged 16 and under were included in the analysis. The most
      common pathology was dental pathology (24.4%), followed by odontogenic cysts
      (18.5%) and mucosal pathology (17.0%). The most frequently encountered lesion was
      the dentigerous cyst (9.4%), followed by fibrous hyperplasia (8.3%), radicular
      cyst (5.2%) and chronic periapical granuloma (5.2%). CONCLUSIONS: In the
      paediatric population, dental pathology and specifically, the dentigerous cyst is
      the most common pathology type sent for histopathology, suggesting a high
      prevalence of pathology of dental origin occurring in Australian children.

PMID- 24861400
TI  - Oral health impacts and quality of life in an urban homeless population.
AB  - BACKGROUND: Homeless people experience a much higher burden of general health
      conditions and have much poorer oral health than the rest of the population. The
      aim of this study was to determine the oral health impacts and general quality of
      life of an urban homeless population. METHODS: A convenience sample of 58 adults
      (dentate n = 56) experiencing homelessness were assessed using a survey which
      included the 14-item Oral Health Impact Profile and the 26-item World Health
      Organization's Quality of Life - short version. A subset (n = 34) also underwent
      a dental examination. RESULTS: The study participants were younger, more likely
      to be Indigenous, smoked daily and avoided dental care because of cost than the
      rest of the population. Dentate homeless adults reported significantly greater
      oral health impacts when compared with the Australian dentate population. General
      quality of life was significantly poorer than for the rest of the population.
      Treatment need was associated with greater oral health impacts. CONCLUSIONS: Poor
      oral health is prevalent and adversely impacts quality of life for homeless
      people, but it is only one of a range of complex social and health challenges
      being faced by these individuals. Dental care should be better integrated within
      homeless support services.

PMID- 24861401
TI  - Management of traumatically intruded young permanent tooth with 40-month follow
      up.
AB  - BACKGROUND: Intrusive luxation injuries often result in severe damage to the
      tooth, periodontal ligament and pulpal tissue. Furthermore, treatment outcome is
      often unpredictable because of the large number of injury related variables which
      influence choice of treatment and prognosis. This report presents the case of a 9
      year-old boy with a 6 mm intruded permanent maxillary central incisor with an
      open apex. METHODS: The treatment option chosen was to wait and watch for
      'spontaneous re-eruption'. At the end of two weeks, the tooth showed signs of
      pulp necrosis and external root resorption. A palatal mucoperiostal flap was
      reflected and endodontic access was established, following which an intracanal
      medicament of calcium hydroxide was applied. By the end of the fifth month, there
      was radiographic evidence of apical barrier formation and by the tenth month, the
      tooth had re-erupted to the level of the adjacent central incisor. Root canal
      treatment was completed at the end of 24 months and the root was reinforced using
      a glass fibre post. RESULTS: At the last follow-up visit (40 months after
      trauma), the tooth was asymptomatic and radiographic examination showed
      satisfactory periapical and periodontal healing. CONCLUSIONS: Spontaneous re
      eruption is possible, even in severely intruded teeth with open apices.

PMID- 24861402
TI  - Regenerative effect of azithromycin on periodontitis with different levels of
      gingival inflammation: three case reports.
AB  - BACKGROUND: Azithromycin is an antibiotic belonging to the macrolides. Previous
      case reports showed that azithromycin has a regenerative effect on periodontal
      tissue in addition to improving periodontal gingival inflammation. Recently, we
      experienced three periodontitis cases, all of which showed severe bone loss.
      However, their gingival inflammatory signs differed greatly. The present case
      reports evaluated the regenerative effects of azithromycin on periodontitis sites
      with different clinical signs of gingival inflammation. METHODS: In Case 1,
      generalized chronic periodontitis with severe gingival inflammation was treated
      with azithromycin before periodontal treatment. In contrast, Case 2 presented
      with few clinical signs of gingival inflammation, but was treated with
      azithromycin prescribed within a day of scaling and root planing. In Case 3,
      teeth with moderate gingival inflammation were treated with azithromycin after a
      series of scaling and root planing. RESULTS: Remarkable alveolar bone growth,
      regardless of baseline gingival inflammation, was noted in all three cases.
      CONCLUSIONS: The use of adjunctive azithromycin in scaling and root planing may
      be effective for periodontal tissue regeneration. This property may be
      independent of the degree of baseline gingival inflammation.

PMID- 24861403
TI  - Expression of nuclear receptors of gingiva in polycystic ovarian syndrome: a
      preliminary case study.
AB  - Oestrogen is mainly responsible for alterations in blood vessels and progesterone
      stimulates the production of inflammatory mediators. In females, during puberty,
      ovulation and pregnancy, there is an increase in the production of sex steroid
      hormones, which results in increased gingival inflammation, characterized by
      gingival enlargement, increased bleeding and crevicular fluid flow. This article
      presents a case of a patient who presented with a complaint of gingival swelling
      and spontaneous bleeding that persisted for more than two months. Her health
      history documented the recently diagnosed presence of polycystic ovarian
      syndrome. Clinical examination revealed enlarged painful gingival tissues, which
      bled when touched. After completion of Phase I therapy, the enlargement did not
      subside and a biopsy sample was taken. This was compared with another patient who
      had the same health condition but did not show any gingival enlargement. Testing
      of tissue samples for oestrogen and progesterone receptors showed the first
      patient to be positive for oestrogen receptors but negative for progesterone,
      whereas the control was negative for both. Positive oestrogen receptors suggest
      that polycystic ovarian syndrome has some effect on the periodontium. The dental
      consequences of this condition, highly prevalent among young females, are
      typically ignored. Further studies warrant establishment of a clinical
      association and future diagnosis. 

PMID- 24861404
TI  - Coincidental diagnosis of tuberculous lymphadenitis: a case report.
AB  - The aim of this case report was to present a case of multiple calcified
      tuberculous lymph nodes found on a panoramic radiograph coincidently diagnosed in
      an endodontic clinic. A detailed discussion on the differential diagnosis of
      similar such calcification found in the same region is also presented. A 14-year
      old girl was referred to our department with the complaint of painless swelling
      in the left side of the lower jaw. Clinical and radiographical examinations were
      performed, leading to the initial diagnosis of chronic periapical abscess. The
      patient's medical history was re-evaluated. Advanced imaging and excisional
      biopsy were performed in order to confirm the final diagnosis. Regarding the
      presenting signs and symptoms of bilateral carious mandibular molars, a
      periapical inflammatory process was considered in the provisional diagnosis. A
      thorough examination and investigations were suggestive of cervical tuberculous
      lymphadenitis (scrofula), and the patient underwent excision of the same. The
      clinician should consider the possibility of chronic granulomatous inflammatory
      lesions in the differential diagnosis of radiopaque lesions. 

PMID- 24861405
TI  - Correct diagnosis for plunging ranula by magnetic resonance imaging.
AB  - Plunging ranulas most commonly occupy the submandibular triangle and misdiagnosis
      inevitably leads to incorrect treatment. Three cases of plunging ranula are
      reported. The correct diagnosis resulted from the characteristic signs of
      magnetic resonance imaging (MRI). Treatment consisted of the total removal of the
      sublingual gland and evacuation of cystic contents by the intraoral approach. The
      cyst gradually regressed and disappeared within two months after surgery as
      confirmed by ultrasonography. All three cases have not experienced recurrence in
      the follow-up period. MRI is a valuable method to correctly diagnosis plunging
      ranula. Total removal of the sublingual gland is the most reliable method to
      treat plunging ranula. 

PMID- 24861406
TI  - Financial burden of dental care among Australian children.

PMID- 24861410
TI  - Microbiocidal effects of various taurolidine containing catheter lock solutions.
AB  - BACKGROUND & AIMS: We have recently shown that a catheter lock solution
      containing taurolidine dramatically decreases catheter-related bloodstream
      infections (CRBSI) in patients on home parenteral nutrition (HPN) when compared
      to heparin. Since several taurolidine formulations are commercially available,
      some of which also contain citrate or heparin, we were interested in the effect
      of these different locks on growth and biofilm formation of fungal, Gram-negative
      and Gram-positive pathogens that are known to impede HPN treatment. METHODS:
      Clinical isolates obtained during CRBSI of HPN patients were grown in the
      presence of catheter locks (2% taurolidine, 1.34% taurolidine-citrate, 1.34%
      taurolidine-citrate-heparin, citrate and heparin) or phosphate buffered saline
      diluted in lysogeny broth medium for bacteria and sabouraud liquid medium for
      yeasts. Biofilm formation, assessed by crystal violet staining, and growth of
      clinical isolates were determined by optical density measurements. RESULTS: We
      found that 12.5* diluted solutions of all taurolidine containing formulations
      completely prevented growth of Escherichia coli, Staphylococcus aureus and
      Candida glabrata. Growth of these microbes was detected earlier in 1.34%
      taurolidine-citrate(-heparin) than in 2% taurolidine, while citrate and heparin
      did not inhibit growth of clinical isolates compared to PBS. No differences in
      biofilm formation were found between taurolidine containing solutions.
      CONCLUSION: Taurolidine containing lock solutions prevent growth of fungal, Gram
      negative and Gram-positive pathogens. While 2% taurolidine appears to be the most
      potent in this respect in this in vitro setting, the relevance of the small
      differences in growth inhibition between the commercially available taurolidine
      containing lock solutions for clinical practice remains to be established.

PMID- 24861411
TI  - Implant decontamination with 2% chlorhexidine during surgical peri-implantitis
      treatment: a randomized, double-blind, controlled trial.
AB  - OBJECTIVE: The objective of this randomized, double-blind, controlled trial was
      to evaluate the clinical, radiographic, and microbiological effects of implant
      surface decontamination with a 2% chlorhexidine (CHX) solution in comparison with
      a 0.12% chlorhexidine + 0.05% cetylpyridinium chloride (CPC) solution during
      resective surgical peri-implantitis treatment. MATERIAL AND METHODS: Forty-four
      patients (108 implants) with peri-implantitis were treated with resective
      surgical treatment consisting of bone re-contouring, surface debridement and
      chemical decontamination, and apically repositioned flap. Patients were randomly
      allocated to decontamination with a 2% CHX solution (test group) or 0.12% CHX +
      0.05% CPC (control group). Clinical and radiographic parameters were recorded
      before treatment (baseline), and at 3, 6, and 12 months after treatment.
      Microbiological parameters were recorded during surgery. RESULTS: Multilevel
      analysis showed no significant differences in bleeding, suppuration, probing
      pocket depth, and radiographic bone loss between control and test group over
      three follow-up measurements (3, 6, and 12 months) from baseline. Both
      decontamination procedures resulted in significant reductions in anaerobic
      bacterial counts on the implant surface, but no significant difference was noted
      between control and test group (mean log 3.37 +/- 2.34 vs. 3.65 +/- 2.87, P =
      0.99). CONCLUSIONS: The use of a 2% CHX solution for implant surface
      decontamination during resective peri-implantitis therapy does not lead to
      improved clinical, radiographic, or microbiological results compared with a 0.12%
      CHX + 0.05% CPC solution. Overall, the additional use of CHX reduces anaerobic
      bacterial load on the implant surface better than mechanical debridement alone,
      but does not seem to enhance clinical treatment outcomes (ClinicalTrials.gov
      number NCT01852253).

PMID- 24861412
TI  - Are public-private partnerships a healthy option? A systematic literature review.
AB  - Governments around the world, but especially in Europe, have increasingly used
      private sector involvement in developing, financing and providing public health
      infrastructure and service delivery through public-private partnerships (PPPs).
      Reasons for this uptake are manifold ranging from rising expenditures for
      refurbishing, maintaining and operating public assets, and increasing constraints
      on government budgets stifle, seeking innovation through private sector acumen
      and aiming for better risk management. Although PPPs have attracted practitioner
      and academic interest over the last two decades, there has been no attempt to
      integrate the general and health management literature to provide a holistic view
      of PPPs in healthcare delivery. This study analyzes over 1400 publications from a
      wide range of disciplines over a 20-year time period. We find that despite the
      scale and significance of the phenomenon, there is relatively limited
      conceptualization and in-depth empirical investigation. Based on bibliographic
      and content analyses, we synthesize formerly dispersed research perspectives into
      a comprehensive multi-dimensional framework of public-private partnerships. In so
      doing, we provide new directions for further research and practice. 

PMID- 24861413
TI  - How potentially serious symptom changes are talked about and managed in COPD
      clinical review consultations: a micro-analysis.
AB  - People with Chronic Obstructive Pulmonary Disease (COPD) are at heightened risk
      of developing lung cancer. Recent research has suggested that in people who have
      the disease, the time between symptom onset and consultation can be long enough
      to significantly affect prognosis. The regular and routine clinical encounters
      that people with COPD engage in provide an opportunity for them to highlight new
      symptoms of concern, and for clinicians to be watchful for new symptomatic
      indicators. We present a micro-analysis of naturalistic data from a corpus of
      such encounters with the aim of exploring the interactional factors within these
      routine consultations which influence when and how new symptoms of concern are
      raised. Our hypothesis is that although the underlying aim of the review
      consultation is the same in both settings, the different consultation structures
      oriented to by nurses and GPs have a tangible effect on how new and concerning
      symptomatic information is introduced. Conversation analysis (CA) was used to
      examine 39 naturalistic review consultation recordings in two clinical settings;
      GP led (n = 16), and practice nurse led (n = 23). We describe three interactional
      formats by which patients chose to present new symptomatic concerns; 'direct',
      'embedded', and 'oblique'. Both settings provided interactional 'slots' for
      patients to offer new and concerning symptomatic information. However, the
      structure of nurse led encounters tended to limit opportunities for patients to
      develop extended symptom narratives which in turn facilitated 'oblique' formats.
      We suggest that the attenuation of the 'oblique' format in this particular
      clinical setting has implications relating to the psycho-social idiosyncrasies of
      lung cancer and the maintenance of interactional conditions that encourage
      patients to disclose new symptomatic concerns.

PMID- 24861414
TI  - Xylem formation can be modeled statistically as a function of primary growth and
      cambium activity.
AB  - Primary (budburst, foliage and shoot) growth and secondary (cambium and xylem)
      growth of plants play a vital role in sequestering atmospheric carbon. However,
      their potential relationships have never been mathematically quantified and the
      underlying physiological mechanisms are unclear. We monitored primary and
      secondary growth in Picea mariana and Abies balsamea on a weekly basis from 2010
      to 2013 at four sites over an altitudinal gradient (25-900 m) in the eastern
      Canadian boreal forest. We determined the timings of onset and termination
      through the fitted functions and their first derivative. We quantified the
      potential relationships between primary growth and secondary growth using the
      mixed-effects model. We found that xylem formation of boreal conifers can be
      modeled as a function of cambium activity, bud phenology, and shoot and needle
      growth, as well as species- and site-specific factors. Our model reveals that
      there may be an optimal mechanism to simultaneously allocate the photosynthetic
      products and stored nonstructural carbon to growth of different organs at
      different times in the growing season. This mathematical link can bridge
      phenological modeling, forest ecosystem productivity and carbon cycle modeling,
      which will certainly contribute to an improved prediction of ecosystem
      productivity and carbon equilibrium. 

PMID- 24861415
TI  - The link between negative affect, vagal tone, and visceral sensitivity in
      quiescent Crohn's disease.
AB  - Autonomic dysfunction and mood disorders are frequently described in Crohn's
      disease (CD) and are known to influence visceral sensitivity. We addressed the
      link between vagal tone, negative affect, and visceral sensitivity in CD patients
      without concomitant features of irritable bowel syndrome (IBS). Rectal
      distensions to a discomfort threshold of 70% and onset of pain were performed in
      nine CD patients in remission and eight healthy controls. Autonomic parameters
      were evaluated with heart rate variability and electrodermal reactivity. We
      showed that CD patients had (i) higher scores of depressive symptomatology (12 +/
      3 in patients vs 4 +/- 1 in controls on the Center for Epidemiologic Studies
      Depression Scale; p = 0.038), (ii) reduced vagal tone (HF 257 +/- 84 ms(2) vs
      1607 +/- 1032 ms(2) , p = 0.043; LF 455 +/- 153 ms(2) vs 1629 +/- 585 ms(2) , p =
      0.047), (iii) decreased sympathetic reactivity during an aversive stimulus, and
      (iv) higher tolerance to rectal distension pressures (43 +/- 3 mmHg vs 30 +/- 2
      mmHg, p = 0.002) and low sensitivity index scores. In conclusion, our results
      provide preliminary evidence that patients with quiescent CD, in the absence of
      IBS, are hyposensate to experimental rectal distension. These data provide
      further evidence that anxiety and depressive symptomatology in addition to
      autonomic dysfunction modulate visceral pain perception in quiescent CD patients
      in the absence of IBS. 

PMID- 24861416
TI  - A standardized trauma care protocol decreased in-hospital mortality of patients
      with severe traumatic brain injury at a teaching hospital in a middle-income
      country.
AB  - INTRODUCTION: Standardized trauma protocols (STP) have reduced morbidity and in
      hospital mortality in mature trauma systems. Most hospitals in low- and middle
      income countries (LMICs) have not implemented STPs, often because of financial
      and logistic limitations. We report the impact of an STP designed for the care of
      trauma patients in the emergency department (ED) at an LMIC hospital on patients
      with severe traumatic brain injury (STBI). METHODS: We developed an STP based on
      generally accepted best practices and damage control resuscitation for a level I
      trauma centre in Colombia. Without a pre-existing trauma registry, we adapted an
      administrative electronic database to capture clinical information of adult
      patients with TBI, a head abbreviated injury score (AIS) >=3, and who presented
      <=12h from injury. Demographics, mechanisms of injury, and injury severity were
      compared. Primary outcome was in-hospital mortality. Secondary outcomes were
      Glasgow Coma Score (GCS), length of hospital and ICU stay, and prevalence of ED
      interventions recommended in the STP. Logistic regression was used to control for
      potential confounders. RESULTS: The pre-STP group was hospitalized between August
      2010 and August 2011, the post-STP group between September 2011 and June 2012.
      There were 108 patients meeting inclusion criteria, 68 pre-STP implementation and
      40 post-STP. The pre- and post-STP groups were similar in age (mean 37.1 vs.
      38.6, p=0.644), head AIS (median 4.5 vs. 4.0, p=0.857), Injury Severity Scale
      (median 25 vs. 25, p=0.757), and initial GCS (median 7 vs. 7, p=0.384). Post-STP
      in-hospital mortality decreased (38% vs. 18%, p=0.024), and discharge GCS
      increased (median 10 vs. 14, p=0.034). After controlling for potential
      confounders, odds of in-hospital mortality post-STP compared to pre-STP were
      0.248 (95%CI: 0.074-0.838, p=0.025). Hospital and ICU stay did not significantly
      change. The use of many ED interventions increased post-STP, including bladder
      catheterization (49% vs. 73%, p=0.015), hypertonic saline (38% vs. 63%, p=0.014),
      arterial blood gas draws (25% vs. 43%, p=0.059), and blood transfusions (3% vs.
      18%, p=0.008). CONCLUSIONS: An STP in an LMIC decreased in-hospital mortality,
      increased discharge GCS, and increased use of vital ED interventions for patients
      with STBI. An STP in an LMIC can be implemented and measured without a pre
      existing trauma registry.

PMID- 24861417
TI  - There is a better way to address the impact of age of blood in trauma patients.

PMID- 24861418
TI  - Effect of free distribution of safety equipment on usage among motorcycle-taxi
      drivers in Tanzania--A cluster randomised controlled trial.
AB  - INTRODUCTION: Deaths due to road traffic injuries, particularly motorcycle
      crashes, have increased rapidly in many African nations and context-specific
      strategies to improve preventative behaviours are needed. Although adhering to
      conspicuity measures by wearing reflective safety vests is a highly effective
      crash prevention strategy and mandated by law among motorcycle-taxi drivers in
      some African countries, actual use is currently low. We aimed to test whether
      eliminating cost-barriers through the provision of free reflective, fluorescent
      motorcycle safety vests would lead to increased utilisation among a high-risk
      population of motorcycle-taxi drivers in Tanzania. METHODS: A cluster randomised
      controlled trial was conducted among 180 motorcycle-taxi drivers. Participants
      randomised to the intervention arm (90) received free, reflective, fluorescent
      vests; participants randomised to the control arm (90) did not receive free
      vests. Participants' use of reflective vests was then observed on city streets
      over a three month period and differential uptake was estimated using mixed
      effects logistic regression. RESULTS: Baseline use of reflective vests was 3.3%
      in both arms. Seventy-nine drivers in the intervention arm and 82 drivers in the
      control arm were observed during follow-up. The average proportion of
      observations during which motorcycle drivers were using a reflective vest was
      9.5% in the intervention arm, compared to 2.0% in the control arm (odds ratio:
      5.5, 95% confidence interval: 1.1-26.9, p-value: 0.04). CONCLUSION: Although
      distribution of free reflective vests led to a statistically significant increase
      in vest usage, the absolute increase was modest. Additional strategies beyond
      removing economic barriers are important to augment adherence to road safety
      behaviours for injury prevention.

PMID- 24861419
TI  - Small bowel obstruction in the emergency department: MDCT features of common and
      uncommon causes.
AB  - Small bowel obstruction is a common condition encountered by the radiologist in
      the emergency department. Though intestinal adhesions and obstructed hernias are
      the most common causes of acute small bowel obstruction, a variety of uncommon
      and rare conditions can cause acute and subacute bowel obstruction. Imaging plays
      a key role in the workup of bowel obstruction by identifying the cause, level,
      and degree of bowel obstruction. In this article, we present a comprehensive
      review of the multi-detector computed tomography features of common and uncommon
      causes of acute and subacute small bowel obstruction. 

PMID- 24861420
TI  - Offline consolidation in implicit sequence learning.
AB  - The goal of this study was to investigate offline memory consolidation with
      regard to general motor skill learning and implicit sequence-specific learning.
      We trained young adults on a serial reaction time task with a retention interval
      of either 24 h (Experiment 1) or 1 week (Experiment 2) between two sessions. We
      manipulated sequence complexity (deterministic vs probabilistic) and motor
      responses (unimanual or vs bimanual). We found no evidence of offline memory
      consolidation for sequence-specific learning with either interval (in the sense
      of no deterioration over the interval but no further improvement either).
      However, we did find evidence of offline enhancement of general motor skill
      learning with both intervals, independent of kind of sequence or kind of
      response. These results suggest that general motor skill learning, but not
      sequence-specific learning, appears to be enhanced during offline intervals in
      implicit sequence learning. 

PMID- 24861423
TI  - Mouse hippocampal explant culture system to study isolated axons.
AB  - BACKGROUND: Studies of neuronal regeneration require examination of axons
      independently of their cell bodies. Several effective strategies have been
      deployed to compartmentalize long axons of the peripheral nervous system (PNS).
      However, current strategies to compartmentalize axons of the central nervous
      system (CNS) may be limited by physical damage to cells during tissue
      dissociation or slicing, perturbation of three-dimensional tissue architecture,
      or insufficient axonal tissue for biological analysis. NEW METHODS: We developed
      a novel mouse neonate whole-hippocampus explant culture system, to probe neuronal
      regeneration in the central nervous system. This system enables imaging,
      biological, and biophysical analysis of isolated axons. RESULTS: We validated
      this model by isolating pure axonal populations. Additionally, cells within the
      explant were viable and amenable to transfection. We implemented the explant
      system to characterize axonal outgrowth following crush injury to the explant at
      the time of harvest, and also a secondary axonal transection injury 2 days post
      culture. The initial crush injury delayed axonal outgrowth; however, axotomy did
      not alter rates of outgrowth up to 1h post-injury, with or without initial tissue
      crush injury. COMPARISON WITH EXISTING METHODS: Our explant system addresses
      shortcomings of other strategies developed to compartmentalize CNS axons. It
      provides a simple method to examine axonal activity and function without
      requiring additional equipment to slice tissue or segregate axons. CONCLUSION:
      Our hippocampal explant model may be used to study axonal response to injury. We
      have demonstrated the feasibility of probing axonal biology, biochemistry, and
      outgrowth free from confounding effects of neuronal cell bodies.

PMID- 24861422
TI  - Use of dynamic weight bearing as a novel end-point for the assessment of
      abdominal pain in the LPS-induced peritonitis model in the rat.
AB  - BACKGROUND: Chronic pelvic pain (CPP) is defined as long-lasting and severe
      pelvic pain persisting over six months in cyclic or non-cyclic chronic manner.
      Various pathologic conditions like endometriosis, abdominal infections, intra
      peritoneal adhesions or infection, underlie CPP which is often the leading
      symptom of the associated diseases. Pharmacological approaches addressing CPP are
      hampered by the absence of a straight-forward, objective, and reliable method for
      the assessment of CPP in rodents. METHOD: In the presented study, the dynamic
      weight bearing system (DWB) was employed for the first time for the evaluation of
      pelvic pain in a rat model of LPS-induced peritonitis. Rats were pretreated with
      the COX-2 inhibitor rofecoxib and PGE2 levels were evaluated in peritoneal
      lavage. RESULTS: DWB analysis revealed that rats treated with LPS showed a relief
      posture by a significantly increased weight distribution to the front when
      compared to vehicle-treated animals. This effect was prevented by rofecoxib
      treatment indicating the sensitivity of the model for pelvic pain related to
      peritonitis. Analysis of the PGE2 levels in the peritoneal fluid indicated a
      correlation with the relief posture intensity. COMPARISON WITH EXISTING
      METHOD(S): In contrast to others weight bearing approaches, the use of DWB allows
      evaluation of spontaneous posture changes as a consequence of pelvic pain.
      CONCLUSION: Taken together, we were able to show, that DWB combined with LPS
      induced peritonitis may deliver a new reliable animal model addressing pelvic
      pain with high construct validity (peritoneal inflammation), and face validity
      (pain related relief posture).

PMID- 24861424
TI  - Simultaneous backward data transmission and power harvesting in an ultrasonic
      transcutaneous energy transfer link employing acoustically dependent electric
      impedance modulation.
AB  - The advancement and miniaturization of body implanted medical devices pose
      several challenges to Ultrasonic Transcutaneous Energy Transfer (UTET), such as
      the need to reduce the size of the piezoelectric resonator, and the need to
      maximize the UTET link power-transfer efficiency. Accordingly, the same
      piezoelectric resonator that is used for energy harvesting at the body implant,
      may also be used for ultrasonic backward data transfer, for instance, through
      impedance modulation. This paper presents physical considerations and design
      guidelines of the body implanted transducer of a UTET link with impedance
      modulation for a backward data transfer. The acoustic matching design procedure
      was based on the 2*2 transfer matrix chain analysis, in addition to the Krimholtz
      Leedom and Matthaei KLM transmission line model. The UTET power transfer was
      carried out at a frequency of 765 kHz, continuous wave (CW) mode. The backward
      data transfer was attained by inserting a 9% load resistance variation around its
      matched value (550 Ohm), resulting in a 12% increase in the acoustic reflection
      coefficient. A backward data transmission rate of 1200 bits/s was experimentally
      demonstrated using amplitude shift keying, simultaneously with an acoustic power
      transfer of 20 mW to the implant.

PMID- 24861425
TI  - Estimating the BSE infection and detectable prevalence in cattle born after 2000
      in Japan.
AB  - We estimated the infection prevalence of BSE in Japanese cattle born in the
      period 2000-2012, using maximum likelihood methods and BSE surveillance data of
      these birth cohorts. From this, we predicted the number of infected cattle and
      test positives in years 2004-2020. Assuming that the infection prevalence decayed
      exponentially over time from 2000, the infection prevalence of the 2000 birth
      cohort was estimated to be 0.00058 which declined exponentially by 0.115 times
      per year in the following years. The number of infected cattle was calculated to
      have peaked in 2005 and would be zero by 2020. The number of test positives was
      calculated to have peaked in 2005 and would be zero by 2012. The number of BSE
      cases actually detected was within the 95% confidence interval of the predicted
      numbers. The detectable prevalence (predicted number of test positives/number of
      cattle tested) was predicted to be highest in 2005. In this year it was predicted
      that one animal out of 160,000 tested would test positive. The detectable
      prevalence would decline exponentially to zero in the subsequent years. 

PMID- 24861426
TI  - Identifying risk factors of avian infectious diseases at household level in
      Poyang Lake region, China.
AB  - Poultry kept in backyard farms are susceptible to acquiring and spreading
      infectious diseases because of free ranging and poor biosecurity measures. Since
      some of these diseases are zoonoses, this is also a significant health concern to
      breeders and their families. Backyard farms are common in rural regions of China.
      However, there is lack of knowledge of backyard poultry in the country. To obtain
      first-hand information of backyard poultry and identify risk factors of avian
      infectious diseases, a cross-sectional study was carried out at household level
      in rural regions around Poyang Lake. A door-to-door survey was conducted to
      collect data on husbandry practices, trading practices of backyard farmers, and
      surrounding environments of backyard farms. Farms were categorized into cases and
      controls based on their history of poultry death. Data were collected for 137
      farms, and the association with occurrence of poultry death event was explored by
      chi-square tests. Results showed that vaccination implementation was a protective
      factor (odds ratio OR=0.40, 95% confidence interval CI: 0.20-0.80, p=0.01), while
      contact with other backyard flocks increased risk (OR=1.72, 95% CI: 0.79-3.74,
      p=0.16). A concept of "farm connectivity" characterized by the density of
      particular land-use types in the vicinity of the farm was proposed to
      characterize the degree of contact between poultry in one household farm and
      those in other household farms. It was found that housing density in a 20-m
      buffer zone of the farmhouse was most significantly associated with poultry death
      occurrence (OR=1.08, 95% CI: 1.02-1.17, p=0.03), and was in agreement with
      observation of villagers. Binary logistic regression was applied to evaluate the
      relationship between poultry death event and density of land-use types in all
      buffer zones. When integrated with vaccination implementation for poultry,
      prediction accuracy of poultry death event reached 72.0%. Results combining
      questionnaire survey with geographical approaches indicated that occurrence of
      poultry death event among backyard farms within a village was heavily impacted by
      farm connectivity. This study provides new insight for the study and help to
      develop more targeted prevention and countermeasure in a typical rural
      environment of China. 

PMID- 24861428
TI  - Epidermal growth factor receptor tyrosine kinase inhibitors in the treatment of
      central nerve system metastases from non-small cell lung cancer.
AB  - Brain metastases (BM) are common and disastrous occurrence in patients with non
      small cell lung cancer (NSCLC). Currently increasing studies suggest remarkable
      efficacy and mild toxicity of the epidermal growth factor tyrosine kinase
      inhibitor (EGFR TKI) in these patients, making targeted therapy an attractive
      option to BM from NSCLC. We here present a review about the use of EGFR-TKIs in
      this context and the following questions would be discussed: Are TKIs capable of
      permeating across brain-blood barrier (BBB)? How to boost exposure of EGFR TKI in
      cerebrospinal fluid to overcome the resistance of refractory metastases? Would
      the combination with other treatment like radiotherapy bring about advanced
      effect? And which patients with BM is the fittest population to EGFR-TKI
      treatment? In fact, though the administration of EGFR TKI only could achieve
      certain effect with limited penetration across BBB, increasing dose and combined
      radiotherapy would carry out better outcome. Unsurprisingly EGFR mutations were
      still the most important predictor of the sensitivity. 

PMID- 24861427
TI  - No interaction between tau and TDP-43 pathologies in either frontotemporal lobar
      degeneration or motor neurone disease.
AB  - INTRODUCTION: Frontotemporal lobar degeneration (FTLD) is classified mainly into
      FTLD-tau and FTLD-TDP according to the protein present within inclusion bodies.
      While such a classification implies only a single type of protein should be
      present, recent studies have demonstrated dual tau and TDP-43 proteinopathy can
      occur, particularly in inherited FTLD. METHODS: We therefore investigated 33
      patients with FTLD-tau (including 9 with MAPT mutation) for TDP-43 pathological
      changes, and 45 patients with FTLD-TDP (including 12 with hexanucleotide
      expansion in C9ORF72 and 12 with GRN mutation), and 23 patients with motor
      neurone disease (3 with hexanucleotide expansion in C9ORF72), for tauopathy.
      RESULTS: TDP-43 pathological changes, of the kind seen in many elderly
      individuals with Alzheimer's disease, were seen in only two FTLD-tau cases--a 70
      year-old male with exon 10 + 13 mutation in MAPT, and a 73-year-old female with
      corticobasal degeneration. Such changes were considered to be secondary and
      probably reflective of advanced age. Conversely, there was generally only scant
      tau pathology, usually only within hippocampus and/or entorhinal cortex, in most
      patients with FTLD-TDP or MND. The extent of tau pathology in FTLD-TDP and MND,
      as with amyloid beta protein, may relate to increased age and possession of
      Apolipoprotein epsilon4 allele. CONCLUSION: We find no predilection or
      predisposition towards an accompanying TDP-43 pathology in patients with FTLD
      tau, irrespective of presence or absence of MAPT mutation, or that genetic
      changes associated with FTLD-TDP predispose towards excessive tauopathy. Where
      the two processes coexist, this is limited and probably causatively independent
      of each other.

PMID- 24861429
TI  - Angiotensin-(1-7) prevent atrial tachycardia induced sodium channel remodeling.
AB  - BACKGROUND: Activation of the renin-angiotensin system plays an important role in
      atrial electrical remodeling; angiotensin-(1-7) (Ang-(1-7)) counterbalances the
      actions of angiotensin II. The aim of this study was to determine the effects of
      Ang-(1-7) on cardiac sodium current (INa ) in a canine model of atrial
      tachycardia. METHODS: Eighteen dogs were randomly assigned to sham, pacing, or
      pacing + Ang-(1-7) groups (n = 6 in each group). Rapid atrial pacing (500
      beats/min) was maintained for 2 weeks, while the dogs in the sham group were not
      paced. Ang-(1-7) (6 MUg/kg/h) was administered intravenously during pacing. Whole
      cell patch clamp techniques were utilized to record INa from canine atrial
      myocytes. Reverse transcription-polymerase chain reaction was used to assess
      possible underlying changes in cardiac Na(+) channels (Nav1.5). RESULTS: Our
      results showed that INa density and expression of the Nav1.5 mRNA significantly
      decreased following pacing (P < 0.05 vs sham); however, the half-activation
      voltage (V1/2act ) and half-inactivation voltage (V1/2inact ) of INa were not
      significantly altered (P > 0.05 vs sham). Ang-(1-7) treatment significantly
      increased INa densities and hyperpolarized V1/2act without concomitant changes in
      V1/2inact but have no effect on the expression of the Nav1.5 gene. CONCLUSIONS:
      Ang-(1-7) significantly increased INa densities, which contributed to improving
      intraatrial conduction and decreasing the likelihood of atrial fibrillation
      maintenance.

PMID- 24861431
TI  - Trends in mortality from chronic liver disease.
AB  - PURPOSE: Mortality from liver cirrhosis has sharply declined in most countries in
      the last few decades, but includes only a fraction of deaths due to chronic liver
      disease. METHODS: Mortality records for liver cirrhosis, liver cancer, viral
      hepatitis, and the three disease categories combined were extracted for the
      period 1995 to 2010 in the Veneto Region (northeastern Italy). The presence of a
      birth cohort effect was assessed by fitting Poisson regression models. The
      alcoholic or viral etiology was retrieved through multiple causes of death
      analysis for the years 2008 to 2010. RESULTS: Liver cirrhosis mortality
      represented only one-third of all liver disease deaths; this proportion was even
      smaller for deaths with a viral etiology and among elderly people. Through the
      study period, age-standardized rates declined by 50% for liver cirrhosis, and by
      30% (world standard) or by 25% (regional standard) for all liver diseases; the
      reduction in proportional mortality was limited to 11%. Mortality rates started
      to decline in subjects born after the early 1920s. CONCLUSIONS: The decline in
      mortality was smaller than that reported by standard statistics for chronic liver
      disease; these statistics should routinely include viral hepatitis and liver
      cancer deaths. When available, multiple causes of death data should be analyzed.

PMID- 24861432
TI  - Regarding "Educating epidemiologists".

PMID- 24861430
TI  - Mental illness and reduction of gun violence and suicide: bringing epidemiologic
      research to policy.
AB  - PURPOSE: This article describes epidemiologic evidence concerning risk of gun
      violence and suicide linked to psychiatric disorders, in contrast to media-fueled
      public perceptions of the dangerousness of mentally ill individuals, and
      evaluates effectiveness of policies and laws designed to prevent firearms injury
      and mortality associated with serious mental illnesses and substance use
      disorders. METHODS: Research concerning public attitudes toward persons with
      mental illness is reviewed and juxtaposed with evidence from benchmark
      epidemiologic and clinical studies of violence and mental illness and of the
      accuracy of psychiatrists' risk assessments. Selected policies and laws designed
      to reduce gun violence in relation to mental illness are critically evaluated;
      evidence-based policy recommendations are presented. RESULTS: Media accounts of
      mass shootings by disturbed individuals galvanize public attention and reinforce
      popular belief that mental illness often results in violence. Epidemiologic
      studies show that the large majority of people with serious mental illnesses are
      never violent. However, mental illness is strongly associated with increased risk
      of suicide, which accounts for over half of US firearms-related fatalities.
      CONCLUSIONS: Policymaking at the interface of gun violence prevention and mental
      illness should be based on epidemiologic data concerning risk to improve the
      effectiveness, feasibility, and fairness of policy initiatives.

PMID- 24861433
TI  - Effects of donor-acceptor groups on the structural and electronic properties of 4
      (methoxymethyl)-6-methyl-5-nitro-2-oxo-1,2-dihydropyridine-3-carbonitrile.
AB  - Quantum chemical calculations on the geometric parameters, harmonic vibrational
      wavenumbers and 1H and 13C nuclear magnetic resonance (NMR) chemical shifts
      values of 4-(methoxymethyl)-6-methyl-5-nitro-2-oxo-1,2-dihydropyridine-3
      carbonitrile [C9H9N3O4] molecule in ground state were performed using the ab
      initio HF and density functional theory (DFT/B3LYP) methods with 6-311++G(d,p)
      basis set. The results of optimized molecular structure were presented and
      compared with X-ray diffraction results. The theoretical vibrational frequencies
      and 1H and 13C NMR chemical shifts values were compared with experimental values
      of the investigated molecule. The observed and calculated values were found to be
      in good agreement. Since the title compound contains different electron-donor and
      -acceptor groups as well as lone pair electrons, and multiple bonds, the effects
      of these groups on the structural and electronic properties are found out. In
      addition, conformational, natural bond orbital (NBO), nonlinear optical (NLO)
      analysis, frontier molecular orbital energies, molecular surfaces, Mulliken
      charges and atomic polar tensor based charges were investigated using HF and DFT
      methods.

PMID- 24861434
TI  - Mannose-binding lectin gene polymorphism and risk factors for cardiovascular
      disease in postmenopausal women.
AB  - BACKGROUND: Inflammatory responses may be altered in postmenopausal women and
      predispose to cardiovascular disease (CVD). Genetic factors can also influence
      susceptibility to CVD. Mannose-binding lectin (MBL) is a component of the innate
      immune system and an activator of the complement cascade. We evaluated the
      association of genetic polymorphism of MBL (MBL2) on risk factors for CVD in
      postmenopausal women. METHODS: In this cross-sectional study, 311 Brazilian women
      (age >=45 years and amenorrhea >=12 months) were included. EXCLUSION CRITERIA:
      presence of previous or current CVD, insulin dependent diabetes, chronic kidney
      disease, autoimmune diseases and cancer. Clinical, anthropometric and biochemical
      assessments were performed to evaluate the cardiovascular risk factors. DNA was
      extracted from buccal cell and polymorphisms at codons 54 and 57 in the MBL2 were
      determined by polymerase chain reaction (PCR). For statistical analysis, the chi
      square and logistic regression (odds ratio, OR) were used. RESULTS: The presence
      of the polymorphic allele for codon 54 was found in 25.8% of women (A/B=22.6%,
      B/B=3.2%) and for codon 57 in 12.2% (A/C=10.8%, C/C=1.4%). The polymorphism at
      codon 54 was significantly associated with the presence of hypertension (OR 0.55,
      95% CI 0.31-0.99, p=0.044) and insulin resistance assessed by HOMA-IR (OR 0.46,
      95% CI 0.24-0.91, p=0.025). No significant associations were observed between the
      polymorphism at codon 57 with risk factors for CVD. CONCLUSION: In postmenopausal
      women, the polymorphism at codon 54 of the MBL2 was associated with lower risk
      for hypertension and insulin resistance that are important risk factors for CVD.

PMID- 24861436
TI  - Midterm results of hybrid perventricular closure of doubly committed subarterial
      ventricular septal defects in pediatric patients.
AB  - OBJECTIVES: To evaluate the safety and efficiency of using hybrid perventricular
      closure in treating pediatric patients with the doubly committed subarterial
      ventricular septal defects (VSD). METHODS: Ninety pediatric patients with doubly
      committed subarterial VSD were enrolled from October 2007 to September 2010 in
      this retrospective study. Among them, 41 underwent open-heart surgery (surgical
      group), while 49 underwent perventricular device closure (perventricular group).
      RESULTS: There was no difference in age (4.36 +/- 3.21 vs. 5.82 +/- 4.32 years, p
      > 0.05) between the two groups. VSD diameter was significantly larger in the
      surgical group than in the perventricular group (5.03 +/- 1.31 vs. 6.03 +/- 1.94
      mm, p < 0.05). There were no major complications such as death, severe valve
      insufficiency, significant residual shunt, or lethal arrhythmias in two groups.
      The perventricular group was associated with a significant reduction of
      transfusion rate (18.4% vs. 97.6%, p < 0.05) as well as mean intensive care unit
      (ICU) stay (0.97 +/- 0.53 vs. 2.78 +/- 3.00 days, p < 0.05) in comparison with
      the surgical group. No difference was noted for complete closure rate between two
      groups at discharge (97.6% vs. 85.7%, p > 0.05) as well as during follow-up
      (97.6% vs. 95.9%, p > 0.05). Perventricular device closure was not associated
      with an increased risk of procedure-induced aortic insufficiency compared with
      the open-heart surgical group during follow-up (14.3% vs. 14.6%, p > 0.05).
      CONCLUSIONS: Hybrid perventricular closure may be an alternative to open-heart
      surgery in selected pediatric patients with doubly committed subarterial VSD.

PMID- 24861435
TI  - Demethylation within the proximal promoter region of human estrogen receptor
      alpha gene correlates with its enhanced expression: Implications for female bias
      in lupus.
AB  - Systemic lupus erythematosus (SLE) is a systemic autoimmune disease primarily
      affecting women. Previous studies have indicated that sex hormone estrogens
      contribute to the female predilection of SLE. Estrogen regulates gene expression
      by translocating estrogen receptors (ER) alpha and beta into the nucleus where
      they induce transcription by binding to estrogen response elements of target
      genes. We have previously observed that expression of ERalpha gene and protein in
      lupus patients is significantly higher than in healthy controls and that
      estradiol up-regulates calcineurin expression via over-expression of ERalpha gene
      in SLE. However, the pathogenesis of over-expression of ERalpha gene is unknown.
      Here we report that enhanced expression of ERalpha mRNA and protein in SLE and
      rheumatoid arthritis is associated with DNA demethylation within the proximal
      promoter region located between -232 and +81 base pair relative to transcription
      start site of human ERalpha gene (GenBank Accession no. AL356311.6). The
      frequency of DNA demethylation was comparable between male and female. These
      findings suggest that estrogen and demethylated ERalpha promoter associated up
      regulated ERalpha genes are two critical factors in the gender biased development
      of autoimmune diseases besides genetic factor. 

PMID- 24861437
TI  - [Impact of omission of axillary dissection on adjuvant therapy in patients with
      metastatic sentinel lymph nodes according to the ACOSOG Z0011 criteria].
AB  - OBJECTIVES: The results of the ACOSOG Z0011 questioned the usefulness of axillary
      lymph node dissection (ALND) in case of metastatic sentinel lymph node (SLN). The
      aim of our study was to assess the impact of the omission of ALND according to
      the inclusion criteria of the ACOSOG Z0011 study if SLN are metastatic but also
      the consequences on prescription of the application of a new standard of care for
      adjuvant treatment. PATIENTS AND METHODS: This retrospective study included,
      between November 2007 and January 2012, patients with T1-T2N0 breast cancer and
      metastatic SLN meeting the criteria for omission of completion ALND according to
      the study of the ACOSOG Z0011. Patients were submitted anonymously and randomly
      in multidisciplinary meeting (MM) 3 times: with complete information including
      ALND (MM1), with information from SLN alone (MM2) and with complete information
      of ALND according to the current protocols in 2013 (MM3). During each
      presentation, we collected the decision of the different adjuvant treatments
      proposed: chemotherapy, hormonal therapy, radiotherapy (with radiation fields).
      Then, we compared therapeutic proposals of the 3 presentations. RESULTS: Fifty
      eight patients were eligible for inclusion criteria of the ACOSOG Z0011.
      Treatments actually proposed during MM1 consisted of 94.8 % of chemotherapy, 77.6
      % of breast and lymph nodes radiotherapy and 91.4 % of hormone therapy. During
      the MM2, there was no significant difference compared to the decision taken
      during MM1. In fact, during MM2, we decided chemotherapy, radiotherapy and
      hormonotherapy respectively in 89.7, 79.3 and 91.4 % of the cases. During the
      MM3, it was shown a significant decrease in the indications of chemotherapy (82.8
      %, P=0.03) and lymph nodes irradiation (56.9 %, P=0.02) compared to the
      therapeutic proposals of the MM1. DISCUSSION AND CONCLUSION: The lack of
      information of ALND does not seem to significantly alter indications for adjuvant
      treatment. Otherwise, the evolution of our references causes a decrease in
      adjuvant therapy.

PMID- 24861438
TI  - [Engagement of fetal head: what have we learnt from ultrasound?].

PMID- 24861439
TI  - [Intra-uterine device and nulliparous women].
AB  - Intra-uterine device (IUD) is one of the birth control methods, which is
      available for nulliparous women, even though misconceptions still remain in
      medical or popular opinion. Only 1.3 % of nulliparous have a IUD as contraception
      in France while it is the second methods used by all women, after pill. The best
      contraception is the one chosen by women; however, the choice for a nulliparous
      of an IUD may be really difficult, despite the increasing number of women wishing
      to use it. Long-acting reversible contraceptives utilization, including IUD, is
      probably one of the issues to decrease the unintended pregnancies. An exhaustive
      and clear information about IUD is necessary to allow an informed and real
      choice. This prescription must consider contraindications and medical conditions
      for safe insertion, especially to avoid infection by screening STD (Chlamydia
      trachomatis and Nesseria gonorrhoeae) in nulliparous women<25 years old.
      Insertion must be effected with usual precautions and short or SL IUD preferred.
      Even if side effects such as expulsion, pelvic pains or dysmenorrhea are more
      frequent by nulliparous, IUD is a first intention choice for contraception to be
      consider, that women could obtain easily, including in emergency contraception
      situation.

PMID- 24861440
TI  - The Arabidopsis transcription factor bZIP11 activates auxin-mediated
      transcription by recruiting the histone acetylation machinery.
AB  - In higher plants, the hormone auxin orchestrates a diverse array of developmental
      and environmental responses mainly exerted via transcriptional control. In its
      absence, auxin-mediated transcription is postulated to be repressed by histone
      deacetylases, which convert chromatin into a highly packed inactive state. Here
      we present a converse mechanism where Arabidopsis bZIP11-related basic leucine
      zipper (bZIP) transcription factors interact via an amino-terminal activation
      domain with ADA2b adapter proteins to recruit the histone acetylation machinery
      to specific auxin-responsive genes. Gain, loss-of-function and pharmacological
      approaches as well as chromatin immunoprecipitation experiments addressing
      various components of the recruitment and acetylation machinery substantiate the
      proposed mechanism. Importantly, G-box-related cis-elements, frequently found in
      auxin-induced promoters, are shown to bind bZIP11-related bZIPs and to function
      as quantitative modulators of auxin-induced transcription. In conclusion, we
      describe a regulatory activation mechanism that serves as a rheostat to modulate
      auxin-mediated responses. 

PMID- 24861441
TI  - Abnormal response to photic stimulation in juvenile myoclonic epilepsy: an EEG
      fMRI study.
AB  - OBJECTIVE: Juvenile myoclonic epilepsy (JME) is a young-onset electroclinical
      syndrome, characterized by myoclonic, generalized tonic-clonic, and possibly
      typical absence seizures. Interictal electroencephalography (EEG) displays 3-6 Hz
      spike/polyspike and wave pattern. Photosensitivity is common. Our aim was to
      explore the blood oxygen level-dependent (BOLD) response evoked by a highly
      provocative photic stimulus in a cohort of people with JME compared to a group of
      nonphotosensitive healthy controls, and to investigate the hemodynamic phenomena
      seen in patients with photosensitive JME. METHODS: We studied 13 JME patients and
      18 healthy controls using EEG-functional magnetic resonance imaging (fMRI)
      performed during low luminance intermittent photic stimulation (IPS). The BOLD
      response to IPS was investigated both in JME and control groups. In
      photosensitive JME subjects, we also performed a dynamic evaluation of BOLD
      signal changes evoked by the photoparoxysmal response (PPR) in a time frame
      ranging from 10 s before the onset of the EEG paroxysm up until 10 s afterward.
      RESULTS: The IPS evoked a positive BOLD response in striate and extrastriate
      visual areas, which was less in JME patients than in controls. Moreover, people
      with JME had a reduced positive BOLD response in the frontoparietal areas and
      putamen but a stronger negative BOLD response in the primary sensorimotor cortex
      (SM1) and in cortical regions belonging to the default mode network (DMN). In
      JME, the dynamic evaluation of BOLD signal changes related to PPR revealed an
      early positive response in the putamen and SM1, followed by BOLD signal
      decrements in the putamen, caudate nuclei, thalami, and SM1. SIGNIFICANCE: Our
      results confirm the hypothesis that people with JME might have an altered
      interaction between the motor circuit and other neuronal networks, with prominent
      involvement of basal ganglia circuitry. The PPR could be a final expression of
      pathogenic phenomena occurring in the striato-thalamocortical system, possibly a
      core feature of system epilepsy JME.

PMID- 24861443
TI  - The RNA-binding protein HuD promotes spinal GAP43 overexpression in
      antiretroviral-induced neuropathy.
AB  - Nucleoside reverse transcriptase inhibitors (NRTIs) are known to produce painful
      neuropathies and to enhance states of pain hypersensitivity produced by HIV-1
      infection in patients with AIDS leading to discontinuation of antiretroviral
      therapy, thus limiting viral suppression strategies. The mechanisms by which
      NRTIs contribute to the development of neuropathic pain are not known. In the
      current study, we tested the hypothesis that HuD, an RNA binding protein known to
      be an essential promoter of neuronal differentiation and survival, might be
      involved in the response to NRTI-induced neuropathy. Antiretroviral neuropathy
      was induced by a single intraperitoneal administration of 2',3'-dideoxycytidine
      (ddC) in mice. HuD was physiologically expressed in the cytoplasm of the soma and
      in axons of neurons within DRG and spinal cord and was considerably overexpressed
      following ddC treatment. ddC up-regulated spinal GAP43 protein, a marker of
      neuroregeneration, and this increase was counteracted by HuD silencing. GAP43 and
      HuD colocalize in DRG and spinal dorsal horn (SDH) axons and administration of an
      anti-GAP43 antibody aggravated the ddC-induced axonal damage. The administration
      of a protein kinase C (PKC) inhibitor or the PKCgamma silencing prevented both
      HuD and GAP43 increased expression. Conversely, treatment with the PKC activator
      PDBu potentiated HuD and GAP43 overexpression, demonstrating the presence of a
      spinal PKC-dependent HuD-GAP43 pathway activated by ddC. These results indicated
      that HuD recruitment and GAP43 protein increase are mechanistically linked events
      involved in the response to antiretroviral-induced neurodegenerative processes. 

PMID- 24861444
TI  - Infrared imaging does not predict the presence of malignancy in patients with
      suspicious radiologic breast abnormalities.
AB  - The NoTouch BreastScan (NTBS) is a non-invasive infrared imaging device which
      measures thermal gradients in breasts using dual infrared cameras and computer
      analysis. We evaluated NTBS as a predictor of breast cancer in patients
      undergoing minimally invasive biopsy. In this IRB-approved prospective trial, 121
      female patients underwent NTBS prior to scheduled tissue biopsy. Twenty-two
      patients were excluded due to uninterpretable scans (n = 18), diagnosis of a
      nonprimary breast malignancy (n = 1), or no biopsy performed (n = 3) for a total
      of 99 patients. Five patients had bilateral breast biopsies and one patient had
      two ipsilateral biopsies, resulting in 105 biopsies. Patients were prospectively
      scanned using a high specificity mode, termed NTBS1. All 99 patients were
      retrospectively re-evaluated in a high sensitivity mode, NTBS2. Of 105 biopsies
      performed in 99 women, 33 (31.4%) were malignant and 72 (68.6%) were benign.
      NTBS1 demonstrated a sensitivity of 45.5% and a specificity of 88.9%. Of 94
      normal contralateral breasts, 9.6% had a positive NTBS1. In the retrospective
      evaluation, NTBS2 demonstrated a sensitivity of 78.8% and a specificity of 48.6%.
      Half (50%) of the normal contralateral breasts had a positive NTBS2. NTBS does
      not accurately predict malignancy in women with suspicious imaging abnormalities.
      The higher sensitivity mode results in an unacceptable number of false positives,
      precluding its use. Infrared imaging did not improve the sensitivity or
      specificity of mammography in this clinical setting.

PMID- 24861442
TI  - Neurologic impairment following closed head injury predicts post-traumatic
      neurogenesis.
AB  - In the mammalian hippocampus, neurogenesis persists into adulthood, and increased
      generation of newborn neurons could be of clinical benefit following concussive
      head injuries. Post-traumatic neurogenesis has been well documented using "open"
      traumatic brain injury (TBI) models in rodents; however, human TBI most commonly
      involves closed head injury. Here we used a closed head injury (CHI) model to
      examine post-traumatic hippocampal neurogenesis in mice. All mice were subjected
      to the same CHI protocol, and a gross-motor based injury severity score was used
      to characterize neurologic impairment 1h after the injury. When analyzed 2weeks
      later, post-traumatic neurogenesis was significantly increased only in mice with
      a high degree of transient neurologic impairment immediately after injury. This
      increase was associated with an early increase in c-fos activity, and subsequent
      reactive astrocytosis and microglial activation in the dentate gyrus. Our results
      demonstrate that the initial degree of neurologic impairment after closed head
      injury predicts the induction of secondary physiologic and pathophysiologic
      processes, and that animals with severe neurologic impairment early after injury
      manifest an increase in post-traumatic neurogenesis in the absence of gross
      anatomic pathology. 

PMID- 24861445
TI  - Electrical and thermal transport properties of intermetallic RCoGe2 (R = Ce and
      La) compounds.
AB  - To investigate the electronic structure of the intermetallic compound CeCoGe2, we
      performed electrical resistivity (rho), Seebeck coefficient (S), and thermal
      conductivity (kappa) measurements in a temperature range of 10-300 K. For
      comparison, the non-magnetic counterpart LaCoGe2 is also studied. It is found
      that CeCoGe2 exhibits a broad maximum in the S(T) near 75 K, at which the sudden
      drop in the rho(T) is observed. Temperature-dependent electrical resistivity and
      the Seebeck coefficient of CeCoGe2 can be described well by a two-band model,
      which reveals the signature of Kondo scattering in CeCoGe2. On the other hand, a
      typical metallic-like behavior is seen in the non-magnetic LaCoGe2 from the
      rho(T) and S(T) studies. Analysis of the thermal conductivity indicates that the
      electronic contribution dominates thermal transport above 100 K in both CeCoGe2
      and LaCoGe2. In addition, it is found that the variation in low-temperature
      lattice thermal conductivity of CeCoGe2 as compared to that of LaCoGe2 is most
      likely due to the phonon-point-defect scattering. 

PMID- 24861447
TI  - Early repolarization is associated with symptoms in patients with type 1 and type
      2 long QT syndrome.
AB  - BACKGROUND: Early repolarization (ER) is associated with an increased risk for
      death from cardiac causes. Recent evidence supports ER's role as a modifier
      and/or predictor of risk in many cardiac conditions. OBJECTIVE: The purpose of
      this study was to determine the prevalence of ER among genotype-positive patients
      with long QT syndrome (LQTS) and evaluate its utility in predicting the risk of
      symptoms. METHODS: ER was defined as QRS slurring and/or notching associated with
      >=1-mV QRS-ST junction (J-point) elevation in at least 2 contiguous leads,
      excluding the anterior precordial leads. The ECG with the most prominent ER was
      used for analysis. Major ER was defined as >= 2-mm J-point elevation. Symptoms of
      LQTS included cardiac syncope, documented polymorphic ventricular tachycardia
      (VT), and resuscitated cardiac arrest. RESULTS: One hundred thirteen patients
      (mean age 41 +/- 19 years; 63 female) were reviewed, among whom 414 (mean 3.7 +/-
      1.5) ECGs were analyzed. Of these, 30 patients (27%) with a history of symptoms.
      Fifty patients (44%) had ER, and 19 patients (17%) had major ER. Patients with
      major ER were not different from patients without major ER with respect to age,
      sex, long QT type, longest QTc recorded, number of patients with QTc >500 ms, or
      use of beta-blockade. Univariate and independent predictors of symptom status
      included the presence of major ER, longest QTc recorded >500 ms, and female sex.
      CONCLUSION: ER >=2 mm was the strongest independent predictor of symptom status
      related to LQTS, along with female sex and QTc >500 ms.

PMID- 24861446
TI  - Sports-related sudden cardiac death in a competitive and a noncompetitive athlete
      population aged 12 to 49 years: data from an unselected nationwide study in
      Denmark.
AB  - BACKGROUND: Preparticipation screening programs have been suggested to reduce the
      numbers of sports-related sudden cardiac deaths (SrSCD). OBJECTIVE: The purpose
      of this study was to identify and characterize all SrSCD aged 12-49 years and to
      address the difference in incidence rates between competitive and noncompetitive
      athletes. METHODS: All deaths among persons aged 12-49 years from 2007-2009 were
      included. Death certificates were reviewed. History of previous admissions to
      hospital was assessed, and discharge summaries and autopsy reports were read.
      Sudden cardiac deaths (SCDs) and SrSCD cases were identified. RESULTS: In the 3
      year period, there were 881 SCDs, of which we identified 44 SrSCD. In
      noncompetitive athletes aged 12-35 years, the incidence rate of SrSCD was 0.43
      (95% confidence interval [CI] 0.16-0.94) per 100,000 athlete person-years vs 2.95
      (95% CI 1.95-4.30) in noncompetitive athletes aged 36-49 years. In competitive
      athletes, the incidence rate of SrSCD was 0.47 (95% CI 0.10-1.14) and 6.64 (95%
      CI 2.86-13.1) per 100,000 athlete person-years in those aged 12-35 years and 36
      49 years, respectively. The incidence rate of SCD in the general population was
      10.7 (95% CI 10.0-11.5) per 100.000 person-years. CONCLUSION: The incidence rates
      of SrSCD in noncompetitive and competitive athletes are not different. The study
      showed an increase in the incidence rate of SrSCD in persons aged 36-49 years in
      both noncompetitive and competitive athletes compared to those aged 12-35 years.
      Importantly, SCD in the general population is much more prevalent than is SrSCD
      in all age groups.

PMID- 24861448
TI  - Impact of atrial fibrillation termination mode during catheter ablation procedure
      on maintenance of sinus rhythm.
AB  - BACKGROUND: Catheter ablation is a common and effective procedure for addressing
      atrial fibrillation (AF) refractory to antiarrhythmic drugs. AF can be terminated
      in 3 modes: (1) directly into sinus rhythm (SR); (2) evolving into regular atrial
      tachycardia (AT) and subsequently into SR; and (3) after direct current (DC)
      cardioversion if AF persists. Scarce data are available on the relationship
      between clinical outcomes and termination mode after 1 catheter ablation.
      OBJECTIVE: The purpose of this study was to evaluate for the first time the
      association between 1-year ablation efficacy and termination mode after repeated
      catheter ablations in patients presenting with persistent or long-standing
      persistent AF. METHODS: This prospective study involved 400 consecutive patients
      (age 62.7 +/- 7.2 years) who underwent catheter ablation for drug-refractory
      persistent AF (4.6 +/- 2.4 months) using a stepwise ablation approach. RESULTS:
      AF was terminated by radiofrequency application directly into SR in 135 patients;
      passing through AT into SR in 195 patients; and through DC cardioversion in 70
      patients. After 1-year follow-up with repeated Holter monitoring, the percentages
      of SR maintenance were 72.6%, 80.0%, and 28.6%, respectively (P < .001). Compared
      with the subjects who were converted directly into SR, the adjusted hazard ratios
      (HRs) of SR maintenance were significantly lower for those who required DC
      cardioversion (HR = 0.54; P < .001) and higher for those converted through AT (HR
      = 1.69; P = .027). The latter association was even stronger in the 104 subjects
      who required a second procedure (HR = 6.25; P = .001). CONCLUSION: Termination of
      AF through AT during catheter ablation was more effective than both DC shock and
      direct SR in maintaining stable SR 1 year after both the first and the second
      procedures.

PMID- 24861449
TI  - Decreased usage and increased effectiveness of percutaneous coronary intervention
      in complex older patients with acute coronary syndromes.
AB  - BACKGROUND: Application of percutaneous coronary intervention (PCI) in patients
      with acute coronary syndromes (ACS) is suboptimal in older frail individuals.
      This study was conducted to verify if background risk is a risk factor for
      underuse and diminished effectiveness of PCI in older patients. METHODS: An
      observational cohort study was conducted using data from the Acute Myocardial
      Infarction in Florence 2 registry, including all ACS hospitalised in 1 year in
      the area of Florence, Italy. Patients aged 75+ years were selected, whose
      background risk was stratified with the Silver Code (SC), a validated tool
      predicting mortality based upon administrative data. Multivariable OR for PCI
      application and HR for 1-year mortality by PCI usage were calculated. RESULTS: In
      698 patients (358 women, mean age 83 years), of whom 176 had ST-segment elevation
      myocardial infarction (STEMI), for each point increase in SC score the odds for
      application of PCI decreased by 11%, whereas the hazard of 1-year mortality
      increased by 10%, adjusting for positive and negative predictors. PCI reduced 1
      year mortality progressively more with increasing SC, with HR (95% CI) of 0.8
      (0.19 to 1.21), 0.41 (0.18 to 0.45), 0.41 (0.23 to 0.74) and 0.26 (0.14 to 0.48)
      for SC of 0-3, 4-6, 7-10 and 11+. CONCLUSIONS: Application of PCI in older ACS
      patients decreased with increasing background risk. This therapeutic attitude
      could not be justified by decreasing effectiveness of PCI in more compromised
      patients: conversely, application of PCI was associated with a long-term survival
      advantage that increased progressively with background risk, as expressed by SC.

PMID- 24861450
TI  - Gestational/perinatal chlorpyrifos exposure is not associated with autistic-like
      behaviors in rodents.
AB  - Although animal models cannot exactly replicate human psychiatric disorders, they
      may be useful to investigate whether the behaviors associated with certain
      exposures in animals parallel those observed in people. According to the most
      current version of the Diagnostic and Statistical Manual of Mental Disorders,
      autism is diagnosed based on (1) persistent deficits in social communication and
      social interaction; and (2) the presence of restricted, repetitive patterns of
      behavior, interests and activities. To address whether developmental chlorpyrifos
      (CPF) exposure was associated with the development of autistic behaviors, a
      literature search was conducted to identify studies in rats and mice involving
      gestational or early postnatal exposure to CPF or CPF oxon (CPO, the active
      metabolite of CPF) and subsequent behavioral testing to assess behaviors related
      to autism. A total of 13 studies conducted in six different laboratories were
      identified. Analysis of these studies found that perinatal CPF exposure was
      generally associated with (1) no effect or increased social communications; (2)
      no effect or increased social encounters; (3) no effect, reduced stereotypies, or
      conflicting findings on stereotypic behaviors; and (4) no effect or increased
      preference for novelty and reduced anxiety in novel environments. These
      behavioral findings are generally inconsistent with the types of behaviors that
      would be expected in children with clinical autism. Based on the results of this
      analysis of rodent model studies involving CPF/CPO exposure, it cannot be
      concluded that gestational and/or perinatal CPF exposure is likely to be
      associated with the development of autism-like behaviors in humans.

PMID- 24861451
TI  - Language development of children born following intracytoplasmic sperm injection
      (ICSI) combined with assisted oocyte activation (AOA).
AB  - BACKGROUND: The effect of assisted reproduction technology (ART) on language
      development is still unclear. Moreover, different techniques are introduced at
      rapid pace and are not always accompanied by extensive follow-up programmes.
      AIMS: To investigate the language development of 3-10-year-old children born
      following ART using intracytoplasmic sperm injection (ICSI) combined with
      assisted oocyte activation (AOA), which is a highly specialized technique applied
      in cases with a history of fertilization failure following conventional ICSI.
      Secondly, a comparison is made between the language development of singletons and
      twins. METHODS & PROCEDURES: Twenty children, six boys and 14 girls, born
      following ICSI combined with AOA and older than 3 years were included in the
      study. The mean age of the children was 5;4 years (range = 3;1-10;4 years; SD =
      1;8 years). Expressive and receptive language development were assessed using the
      Clinical Evaluation of Language Fundamentals (CELF-IV-NL) for children older than
      5 years and the Reynell Developmental Language Scales (RTOS) for children younger
      than or equal to 5 years. OUTCOMES & RESULTS: The mean total score for language
      ability (in percentiles) was 56.8 (SD = 33.6), which corresponds to normal
      language skills. Significantly higher scores were found for AOA singletons
      compared with twins. For the general language, none of the children scored within
      the clinical zone for language disability corresponding with a percentile lower
      than 5. CONCLUSION & IMPLICATIONS: This study presents the first data concerning
      language outcome in 3-10-year-old children born following AOA. General language
      scores of the AOA children in this study are located within the normal ranges.
      The language development of singletons was significantly better compared with
      twins. Although the results are reassuring for language development, in future
      long-term follow-up studies in this population are necessary.

PMID- 24861452
TI  - Association mapping of agro-morphological characters among the global collection
      of finger millet genotypes using genomic SSR markers.
AB  - Identification of alleles responsible for various agro-morphological characters
      is a major concern to further improve the finger millet germplasm. Forty-six
      genomic SSRs were used for genetic analysis and population structure analysis of
      a global collection of 190 finger millet genotypes and fifteen agro-morphological
      characters were evaluated. The overall results showed that Asian genotypes were
      smaller in height, smaller flag leaf length, less basal tiller number, early
      flowering and early maturity nature, small ear head length, and smaller in length
      of longest finger. The 46 SSRs yielded 90 scorable alleles and the polymorphism
      information content values varied from 0.292 to 0.703 at an average of 0.442. The
      gene diversity was in the range of 0.355 to 0.750 with an average value of 0.528.
      The 46 genomic SSR loci grouped the 190 finger millet genotypes into two major
      clusters based on their geographical origin by the both phylogenetic clustering
      and population structure analysis by STRUCTURE software. Association mapping of
      QTLs for 15 agro-morphological characters with 46 genomic SSRs resulted in
      identification of five markers were linked to QTLs of four traits at a
      significant threshold (P) level of <= 0.01 and <= 0.001. The QTL for basal tiller
      number was strongly associated with the locus UGEP81 at a P value of 0.001 by
      explaining the phenotypic variance (R (2)) of 10.8%. The QTL for days to 50%
      flowering was linked by two SSR loci UGEP77 and UGEP90, explained 10 and 8.7% of
      R (2) respectively at a P value of 0.01. The SSR marker, FM9 found to have strong
      association to two agro-morphological traits, flag leaf width (P-0.001, R(2)-14.1
      %) and plant height (P-0.001, R(2)-11.2%). The markers linked to the QTLs for
      above agro-morphological characters found in the present study can be further
      used for cloning of the full length gene, fine mapping and their further use in
      the marker assisted breeding programmes for introgression of alleles into locally
      well adapted germplasm.

PMID- 24861453
TI  - Low-carbohydrate diets for athletes: what evidence?

PMID- 24861454
TI  - Demise of the fittest: are we  destroying our biggest talents?

PMID- 24861455
TI  - Stochastic localization of microswimmers by photon nudging.
AB  - Force-free trapping and steering of single photophoretically self-propelled Janus
      type particles using a feedback mechanism is experimentally demonstrated.
      Realtime information on particle position and orientation is used to switch the
      self-propulsion mechanism of the particle optically. The orientational Brownian
      motion of the particle thereby provides the reorientation mechanism for the
      microswimmer. The particle size dependence of the photophoretic propulsion
      velocity reveals that photon nudging provides an increased position accuracy for
      decreasing particle radius. The explored steering mechanism is suitable for
      navigation in complex biological environments and in-depth studies of collective
      swimming effects. 

PMID- 24861456
TI  - Natural defense by saliva and mucosa against oral infection by Leptospira.
AB  - Leptospirosis caused by drinking water has not been as frequently reported as
      percutaneous infection. Resistance to oral infection by pathogenic Leptospira was
      examined in an experimental hamster infection model. The results suggested some
      natural defenses against oral infection by Leptospira. First, we found that
      characteristic linear agglutination of Leptospira rapidly occurs when mixed with
      human saliva. That human saliva attenuated the infectivity of the treated
      leptospires by its agglutination activity suggested saliva to be the first line
      of defense against oral infection by leptospires. Second, only 10(1) Leptospira
      organisms caused death after submucosal injection into oral mucosa in hamsters,
      but oral infection with drinking water containing 10(5) organisms/mL did not
      cause death. This result showed that the mucosa plays the role of a physical
      barrier. Third, hamsters intragastrically infected by leptospires, with doses
      lethal to hamsters in oral infection, showed no signs of illness, which suggested
      that gastric acid plays an important role in preventing oral infection. Based on
      these results, saliva, mucosa, and gastric acid make up a natural defense, which
      confers high resistance to hosts against oral infection by leptospires. 

PMID- 24861457
TI  - Tailoring photoluminescence properties in ionic nanoparticle networks.
AB  - To investigate the original and promising luminescence properties of ionic
      nanoparticle networks (INN), various material compositions were investigated. In
      this work, the linker used to network the silica nanoparticles was varied;
      numerous substituted or non-substituted imidazolium, pyrazolium and pyridinium
      linkers are presented. Photoluminescence experiments on the INN hybrid materials
      revealed strong emission bands over a broad range in the visible region of the
      light spectrum. Varying the aromatic linker between the imidazolium units induced
      clear shifts of the emission maxima up to 100 nm, as a consequence of pi-pi
      stacking interactions. Steric hindrance and inductive effects of the
      substituents, introduced on the aromatic units, also strongly influenced the
      luminescence properties of the materials by modifying the pi-pi stacking between
      the imidazolium rings. Small and wide-angle X-ray scattering (SAXS, WAXS)
      experiments revealed a clear trend between the obtained structural parameters
      (short-range order parameter and distance of the aromatic units within the hybrid
      material) and the luminescence quantum yields of the INN materials. 

PMID- 24861459
TI  - Application of concepts from cross-recurrence analysis in speech production: an
      overview and comparison with other nonlinear methods.
AB  - PURPOSE: The aim of this article was to introduce an important tool, cross
      recurrence analysis, to speech production applications by showing how it can be
      adapted to evaluate the similarity of multivariate patterns of articulatory
      motion. The method differs from classical applications of cross-recurrence
      analysis because no phase space reconstruction is conducted, and a cleaning
      algorithm removes the artifacts from the recurrence plot. The main features of
      the proposed approach are robustness to nonstationarity and efficient separation
      of amplitude variability from temporal variability. METHOD: The authors tested
      these claims by applying their method to synthetic stimuli whose variability had
      been carefully controlled. The proposed method was also demonstrated in a
      practical application: It was used to investigate the role of biomechanical
      constraints in articulatory reorganization as a consequence of speeded repetition
      of CVCV utterances containing a labial and a coronal consonant. RESULTS: Overall,
      the proposed approach provided more reliable results than other methods,
      particularly in the presence of high variability. CONCLUSION: The proposed method
      is a useful and appropriate tool for quantifying similarity and dissimilarity in
      patterns of speech articulator movement, especially in such research areas as
      speech errors and pathologies, where unpredictable divergent behavior is
      expected.

PMID- 24861458
TI  - What should be the goal of advance care planning?

PMID- 24861461
TI  - Municipality and Neighborhood Influences on Volunteering in Later Life.
AB  - This article explores the relationships between municipality features and
      volunteering by older adults. In the literature, strong evidence exists of the
      influence of place on older people's health. However, the question how
      neighborhoods and municipalities promote or hinder volunteer participation
      remains under-explored. Data for the research are derived from the Belgian Aging
      Studies. We estimate logistic multilevel models for older individuals' engagement
      in volunteering across 141 municipalities in Belgium (N = 67,144). Analysis shows
      that neighborhood connectedness, neighborhood satisfaction, home ownership, and
      presence of services predict voluntary engagement at older ages. The findings
      support that perceptions and quality of social resources that relate to
      neighborhoods may be important factors to explain volunteering among older
      adults. Moreover, the findings suggest that volunteering in later life must be
      considered within a broader framework.

PMID- 24861460
TI  - Percutaneous nerve evaluation based on electrode placement under control of
      autonomic innervation.
AB  - BACKGROUND: Foramen needle electrode placement for percutaneous nerve evaluation
      (PNE) is currently carried out while observing the somatic motor response. This
      study investigated electrode placement while observing the autonomic as well as
      the somatic response. METHODS: A consecutive series of ten patients (seven women)
      with a median age of 51.9 (range 30-75) years undergoing PNE for faecal
      incontinence (n = 6) and obstipation (n = 4) were investigated prospectively.
      Electrode placement was carried out under simultaneous electromyography (EMG) of
      the external anal sphincter (EAS) and internal anal sphincter (IAS) and
      cystomanometry. RESULTS: PNE under control of somatic and autonomic nerve
      responses was carried out in all patients. In three out of ten patients, initial
      needle electrode placement showed single evoked EMG signals from the EAS. Final
      electrode placement resulted in adequate somatic motor and autonomic responses in
      all patients. Comparison of the increases in IAS EMG amplitude on the right and
      left stimulation sites for sacral nerves S3 and S4 demonstrated significant
      differences [S3 right: median 15.3 (interquartile range (IQR) 10.4; 20.1) uV vs.
      S3 left: median 11.6 (IQR 8.6; 16.0) uV, p = 0.034 and S4 right: median 24.1 (IQR
      20.1; 37.2) uV vs. S4 left: median 12.0 (IQR 10.7; 13.7) uV, p = 0.012].
      Stimulation-induced bladder activation was achieved in all seven patients with
      concomitant urinary dysfunction. CONCLUSIONS: Control of not just the somatic
      motor response but also the autonomic nerve response during foramen needle
      electrode placement may objectify PNE.

PMID- 24861462
TI  - Asymmetric Garratt-Braverman cyclization: a route to axially chiral aryl
      naphthalene-amino acid hybrids.
AB  - We report the first example of a highly diastereoselective Garratt-Braverman
      cyclization leading to the synthesis of chiral aryl naphthalene-amino acid
      hybrids in excellent yields. The stereogenecity in the amino acid has induced
      high diastereoselectivity for the reaction. Computations based on density
      functional theory indicated a lower activation free energy barrier for the M
      isomer as compared to that for the P diastereomer (DeltaDeltaG = 3.48 kcal/mol).
      Comparison of the recorded CD spectrum of the product with the calculated one
      also supported the preferential formation of the M diastereomer. 

PMID- 24861464
TI  - Inhibitors of enhancer of zeste homolog 2 (EZH2) activate tumor-suppressor
      microRNAs in human cancer cells.
AB  - Enhancer of zeste homolog 2 (EZH2) enhances tumorigenesis and is commonly
      overexpressed in several types of cancer. To investigate the anticancer effects
      of EZH2 inhibitors, microRNA (miRNA) expression profiles were examined in gastric
      and liver cancer cells treated with suberoylanilide hydroxamic acid (SAHA) and 3
      deazaneplanocin A (DZNep). We confirmed that SAHA and DZNep suppressed EZH2
      expression in AGS and HepG2 cells and inhibited their proliferation. The results
      of microarray analyses demonstrated that miR-1246 was commonly upregulated in
      cancer cells by treatment with SAHA and DZNep. MiR-302a and miR-4448 were
      markedly upregulated by treatment with SAHA and DZNep, respectively. DYRK1A,
      CDK2, BMI-1 and Girdin, which are targets of miR-1246, miR-302a and miR-4448,
      were suppressed by treatment with SAHA and DZNep, leading to apoptosis, cell
      cycle arrest and reduced migration of AGS and HepG2 cells. ChIP assay revealed
      that SAHA and DZNep inhibited the binding of EZH2 to the promoter regions of miR
      1246, miR-302a and miR-4448. These findings suggest that EZH2 inhibitors such as
      SAHA and DZNep exert multiple anticancer effects through activation of tumor
      suppressor miRNAs. 

PMID- 24861463
TI  - Regulation of the pentose phosphate pathway by an androgen receptor-mTOR-mediated
      mechanism and its role in prostate cancer cell growth.
AB  - Cancer cells display an increased demand for glucose. Therefore, identifying the
      specific aspects of glucose metabolism that are involved in the pathogenesis of
      cancer may uncover novel therapeutic nodes. Recently, there has been a renewed
      interest in the role of the pentose phosphate pathway in cancer. This metabolic
      pathway is advantageous for rapidly growing cells because it provides nucleotide
      precursors and helps regenerate the reducing agent NADPH, which can contribute to
      reactive oxygen species (ROS) scavenging. Correspondingly, clinical data suggest
      glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the pentose
      phosphate pathway, is upregulated in prostate cancer. We hypothesized that
      androgen receptor (AR) signaling, which plays an essential role in the disease,
      mediated prostate cancer cell growth in part by increasing flux through the
      pentose phosphate pathway. Here, we determined that G6PD, NADPH and ribose
      synthesis were all increased by AR signaling. Further, this process was necessary
      to modulate ROS levels. Pharmacological or molecular inhibition of G6PD abolished
      these effects and blocked androgen-mediated cell growth. Mechanistically,
      regulation of G6PD via AR in both hormone-sensitive and castration-resistant
      models of prostate cancer was abolished following rapamycin treatment, indicating
      that AR increased flux through the pentose phosphate pathway by the mammalian
      target of rapamycin (mTOR)-mediated upregulation of G6PD. Accordingly, in two
      separate mouse models of Pten deletion/elevated mTOR signaling, Pb-Cre;Pten(f/f)
      and K8-CreER(T2);Pten(f/f), G6PD levels correlated with prostate cancer
      progression in vivo. Importantly, G6PD levels remained high during progression to
      castration-resistant prostate cancer. Taken together, our data suggest that AR
      signaling can promote prostate cancer through the upregulation of G6PD and
      therefore, the flux of sugars through the pentose phosphate pathway. Hence, these
      findings support a vital role for other metabolic pathways (that is, not
      glycolysis) in prostate cancer cell growth and maintenance. 

PMID- 24861465
TI  - A detached arthroscopic lens within the shoulder joint: a case report.
AB  - Shoulder arthroscopy has become a common procedure in today's orthopedic
      practice. The safety of this procedure has been well established, but there are
      some complications associated with every surgical procedure both minor and major.
      In the present era, with advanced arthroscopic instruments, it is rare to
      encounter the problem of instrument breakage during arthroscopic surgery. Here,
      we report an unusual case in which we found a detached arthroscopic lens within
      the shoulder joint. A 58-year-old male patient who was previously operated for
      shoulder arthroscopy for the treatment of impingement syndrome combined with
      shoulder stiffness. We performed shoulder arthroscopy again and removed the
      detached lens arthroscopically. This case warrants the need for the surgeon and
      the operating room staff to be well acquainted with the arthroscopic instruments
      and to check the instruments properly before and after the completion of the
      procedure. If the operating room staff would have identified the damage to the
      scope, encountered during the primary operation, we could have avoided the second
      procedure to remove the lens. 

PMID- 24861466
TI  - Incidence of cannot intubate-cannot ventilate (CICV): results of a 3-year
      retrospective multicenter clinical study in a network of university hospitals.
AB  - PURPOSE: The purpose of this study was to investigate the incidence of cannot
      intubate-cannot ventilate (CICV) during general anesthesia during a 3-year period
      in a network of university hospitals and to evaluate the events related to it.
      METHODS: A retrospective multicenter questionnaire survey of CICV, based on
      medical record review, was conducted over a 3-year period (January 2010-December
      2012) in Hokkaido, Japan. All cases were assessed in terms of the suspected risk
      factors of CICV, the clinical course during anesthesia, and the prognosis.
      RESULTS: Responses were obtained from 20 of 21 institutions (95%) surveyed. The
      incidence of CICV was 3 of 97,854 cases conducted under general anesthesia
      (0.003%). All incidents occurred during induction of general anesthesia. In two
      of the three cases, difficult airway was predicted preoperatively. In all these
      three cases, mask ventilation became impossible after repeated intubation
      attempts with devices such as the Macintosh laryngoscope, the Airwayscope, or a
      fiberoptic bronchoscope. A laryngeal mask was inserted in one case, but the lungs
      could not be adequately ventilated. Emergency tracheotomy was eventually
      performed in all the CICV cases. Although two of the patients did not have
      postoperative neurological sequelae, severe and permanent brain damage occurred
      in one patient. CONCLUSION: In our survey, we found that the incidence of CICV
      during a 3-year period (2010-2012) was 0.003% or 1 in 32,000 cases. The three
      CICV situations occurred after repeated intubation attempts with multiple
      devices. The appropriate airway devices to be used in a particular difficult
      airway situation should be carefully considered before performing multiple
      attempts.

PMID- 24861467
TI  - The association between prolactin, high-sensitivity C-reactive protein and
      Framingham risk score in menopause.
AB  - AIMS: To evaluate the association between serum prolactin, high-sensitivity C
      reactive protein (hs-CRP) levels and cardiovascular disease risk in
      postmenopausal women regarding the Framingham Risk Score (FRS). METHODS: Fifty
      eight menopausal women were enrolled into the cross-sectional study. All
      participants had 24-hour ambulatory blood pressure monitoring, echocardiography,
      electrocardiography, and carotid intima-media thickness measurement. Blood
      samples were obtained for prolactin, hs-CRP, lipid profile, fasting glucose, and
      insulin. RESULTS: Among the participants, 67.24% had a FRS <10%, and 32.75% had a
      FRS >=10%. Levels of prolactin and hs-CRP did not differ between the FRS groups.
      In the FRS <10% group, significantly higher levels of prolactin were found. Cases
      with hypertension have significantly higher levels of hs-CRP. Prolactin and hs
      CRP were found to be associated with hypertension in the FRS <10% and >=10%
      groups, respectively. CONCLUSIONS: Hypertensive postmenopausal women with low
      risk for cardiovascular diseases have increased levels of prolactin, suggesting a
      possible role in the pathogenesis of hypertension. The correlation of hs-CRP with
      systolic blood pressure can be interpreted as a potential effect of hypertensive
      heart disease reflecting a state of high-risk milieu with elevated inflammatory
      markers.

PMID- 24861468
TI  - Discrepancy between self-reported and interviewed psychosis risk symptoms:
      auditory distortions are the most reliably reported symptom by self-report.
AB  - AIM: In the recent literature, there has been growing interest in assessment
      methods for detecting increased risk of developing psychosis. Self-report methods
      are popular but may lead to different results compared to clinical interviews.
      METHODS: The difference in psychosis risk scores was tested between self-reported
      psychosis risk symptoms (PROD-SR) and self-reported symptoms additionally
      confirmed by interview (PROD-SR + I). The symptom categories were derived from 12
      common psychosis risk symptoms included in the PROD screening instrument. The
      data were collected by questionnaires and interviews conducted with 395
      adolescents (mean age 15.3 years) in an early intervention and detection team,
      JERI, at Helsinki University Central Hospital, Finland. RESULTS: The results show
      a significant difference between the PROD-SR risk symptom sum scores and the PROD
      SR + I risk symptom sum scores (N = 395; Z = -15.123; P < 0.001). In an item-by
      item analysis, the item 'Disorders in connection with hearing' had the strongest
      kappa value (0.827) agreement between an interviewed and self-report psychosis
      risk item. Agreement in most items remained between slight and substantial (kappa
      values from 0.082 to 0.649). CONCLUSIONS: The results suggest that there is a
      significant difference between psychosis risk symptom responses collected by self
      report and self-report responses which are additionally confirmed by interview.
      Auditory disorders are the most reliably reported item with self-report.

PMID- 24861469
TI  - Direct asymmetric dearomatization of pyridines and pyrazines by iridium-catalyzed
      allylic amination reactions.
AB  - The first iridium-catalyzed intramolecular asymmetric allylic dearomatization
      reaction of pyridines and pyrazines has been realized. 2,3-Dihydroindolizine and
      6,7-dihydropyrrolo[1,2-a]pyrazine derivatives were obtained with excellent yields
      and enantioselectivity. This methodology features dearomatization by direct N
      allylic alkylation of pyridines or pyrazines under mild reaction conditions. 

PMID- 24861470
TI  - Effects of co-exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin and polychlorinated
      biphenyls on nonalcoholic fatty liver disease in mice.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and polychlorinated biphenyls (PCBs)
      are persistent organic pollutants which coexist in environment, and human are co
      exposed to these chemicals. Our present study was aimed to investigate the
      possible enhanced nonalcoholic fatty liver disease (NAFLD) in ApoE(-/-) mice co
      exposed to TCDD and PCBs and to reveal the potential mechanisms involved in. Male
      ApoE(-/-) mice were exposed to TCDD (15 MUg/kg) and Aroclor1254 (55 mg/kg, a
      representative mixture of PCBs) alone or in combination by intraperitoneal
      injection four times over a 6-week period. Those mice co-exposed to PCBs and TCDD
      developed serious liver steatosis, necrosis, and inflammatory stimuli.
      Interestingly, all treatment induced hepatic cytochrome P450 1A1 (CYP1A1)
      expression, but the maximal level of CYP1A1 was not observed in the co-exposure
      group. Furthermore, microarray analysis by ingenuity pathway analysis software
      showed that the nuclear factor-erythroid 2-related factor 2 (Nrf2)-mediated
      oxidative stress response pathway was significantly activated following co
      exposure to TCDD and PCBs. Our data demonstrated that co-exposure to TCDD and
      PCBs markedly worsen NAFLD in ApoE(-/-) mice.

PMID- 24861471
TI  - LAT gel, a powerful tool underused in the repair of paediatric lacerations.
AB  - Paediatric lacerations presenting to emergency departments are a common cause of
      referral to surgical specialties in the UK. LAT gel (lidocaine, adrenaline, and
      tetracaine) is a safe and effective topical anaesthetic that can aid with the
      closure of uncomplicated lacerations, particularly in the paediatric trauma
      setting. The benefits to both the patient and management in terms of the
      avoidance of a general anaesthetic and the freeing up of hospital resources (e.g.
      beds, staffing, emergency theatre) make it an invaluable tool in the arsenal of
      the emergency department. The authors describe a reliable method of
      anaesthetizing lacerations with LAT gel and question its underuse within the
      emergency departments in the South West region of the UK. 

PMID- 24861472
TI  - Total alloplastic temporomandibular joint reconstruction using Biomet stock
      prostheses: the University of Florida experience.
AB  - The purpose of this study was to report the subjective and objective outcomes of
      temporomandibular joint (TMJ) replacement with Biomet stock prostheses at a
      single institution in Florida. In this retrospective study, patients who
      underwent TMJ replacement using a Biomet stock prosthesis from 2005 to 2012 were
      analyzed. Subjective (pain, diet) and objective (maximal incisal opening)
      information was obtained. In addition, a quality of life measure was obtained pre
      and postoperatively. Significance was set at <0.01. Thirty-six patients (26
      bilateral, 6 left, and 4 right) who underwent TMJ replacement using a Biomet
      stock prosthesis were eligible for the study. Maximal incisal opening improved
      from 26.1mm preoperatively to a mean of 34.4mm postoperatively. The pain score
      decreased from 7.9 preoperatively to a mean of 3.8 postoperatively. Diet
      restriction decreased from 6.8 preoperatively to a mean of 3.5 postoperatively.
      Quality of life improved from a median of 4 preoperatively to a postoperative
      median of 2. Four implants were removed/replaced because of heterotopic bone
      formation, infection, and/or loose hardware. Follow-up ranged from 6 to 83
      months. Overall, TMJ reconstruction using the Biomet stock joint is effective and
      safe in this patient population. 

PMID- 24861473
TI  - Intraoperative ultrasonography is useful in surgical management of neck
      metastases in differentiated thyroid cancers.
AB  - Differentiated thyroid carcinomas are the most common malignancies of endocrine
      organs. Metastases to cervical lymph nodes occur in 20-50% of cases. Recurrence
      and survival rates are closely related to the type of surgery performed. High
      resolution ultrasonography (USG) is a sensitive imaging method used to detect
      occult lymph node metastases in patients with thyroid cancer. We evaluated how
      intraoperative USG affected surgical success. This was a retrospective study
      comparing two groups of patients with thyroid carcinoma who underwent cervical
      lymph node dissection. A total of 101 patients (33 males and 68 females) were
      included. Group 1 included 53 patients who underwent surgery with intraoperative
      USG guidance. Group 2 included 48 patients who underwent surgery without the use
      of USG. All patients were followed up (mean 23 months; range 5-44 months) with
      thyroglobulin measurements and USG evaluations. Group 1 (intraoperative USG) had
      a residual/recurrent tumor rate of 1.9% (1/53 patients). Group 2 had a
      residual/recurrent tumor rate of 12.5% (6/48 patients). A statistically
      significant difference appeared between the residual/recurrent tumor rates in
      Groups 1 and 2 (p<0.05). In addition to its classical use in diagnosis and follow
      up, intraoperative use of high-resolution USG can improve surgical success and
      may decrease the number of residual/recurrent tumors encountered during follow
      up.

PMID- 24861474
TI  - The effect of oral contraceptive different patterns of use on circulating IGF-1
      and bone mineral density in healthy premenopausal women.
AB  - Both insulin-like growth factor-1(IGF-1) and oral contraceptive (OC) use have
      been linked to premenopausal breast and colorectal cancers, osteoporosis and
      cardiovascular disease. Understanding the effects of different patterns of use of
      OC on IGF-1 levels and bone mineral density (BMD) may offer insight into its
      influence on osteoporosis. We conducted a cross-sectional study, which included
      135 women, who were then divided into three groups: Group A who were OC current
      users, 41 women; Group B who never use OC, 51 women; and Group C who were past
      users of OC, 41 women. Each patient completed a questionnaire on demographic
      parameters, marital state history and contraception history including duration of
      use and type of contraceptive pills or used method. Lower-end radius, proximal
      femur and lumbar spine BMD were measured by dual-energy X-ray absorptiometry. IGF
      1 was assessed with chemiluminescent immunometric assay. The three groups were
      similar in total body T value of BMD (with slight better results in past users
      than the other two groups but it was statistically insignificant difference), and
      past users showed significantly higher BMD values compared to current users at
      spine, femur and forearm. Nonusers also had better BMD values compared to current
      users (spine and forearm BMD). Among past users, the mean level of circulating
      IGF-1 was higher than the other two groups and that difference was statistically
      significant. Past OC use and/or nonuse has a more favorable impact on BMD
      compared to current use and that this relationship is in part mediated by IGF-1.
      Hence, it appears that OC use is beneficial to BMD if used in the past and then
      discontinued or if never used at all compared to current use. 

PMID- 24861475
TI  - The effects of sensorial denervation on the ovarian function, by the local
      administration of capsaicin, depend on the day of the oestrous cycle when the
      treatment was performed.
AB  - There is evidence that sensory innervation plays a role in the regulation of
      puberty. The present study investigates the effects of functional sensorial
      desensitisation induced by capsaicin administration to adult female rats in the
      days of diestrus 1, diestrus 2, pro-oestrus or oestrus on ovulation and serum
      oestradiol and progesterone concentration. The animals were allotted at random to
      one of the following groups: (1) animals with capsaicin administration into the
      bursa ovarica (local administration) (2) animals with vehicle administration into
      the bursa ovarica and (3) untreated animals group. The animals treated were
      killed on the day of oestrus after three consecutive 4-day oestrous cycles. No
      differences were observed in oestrous cyclicity or the average number of ova shed
      between the sensorial desensitisation animals and the vehicle-treated groups.
      Capsaicin administration resulted in a significant increase in the intra-ovarian
      noradrenaline levels in the day of diestrus 2 and pro-oestrus. Serum oestradiol
      and progesterone concentrations were different, depending on the day of the
      oestrous cycle in which the treatment was performed. These results suggest that
      in adult normal female rats, ovarian sensorial innervations participate together
      with the sympathetic innervation in the ovarian function regulating the hormone
      secretion and this participation varies along the oestrous cycle. 

PMID- 24861478
TI  - Part 2: ultrastructural changes of fibrin networks during three phases of
      pregnancy: a qualitative investigation.
AB  - INTRODUCTION: Normal pregnancy is characterized by significant alterations in the
      haemostatic system accompanied by an augmented risk of thrombosis. MATERIALS AND
      METHODS: The fibrin network ultrastructure of different phases of pregnancy,
      namely early pregnancy (week 8-14), late pregnancy (week 36-40) as well as post
      partum (week 6-8 after birth) were compared with nonpregnant fibrin networks as
      well as each other to establish whether differences in fibrin network morphology
      exist during pregnancy. Scanning electron microscopy was employed to analyse
      fibrin network morphology. RESULTS: The fibrin networks from all phases of
      pregnancy appeared similar to each other, exhibiting prominent coagulant
      formation, an increase in the formation of minor, thin fibers, and the presence
      of granular globules. All three phases, however, differ from the typical fibrin
      network ultrastructure exhibited by the fibrin networks from nonpregnant
      individuals. The increase in estrogen associated with pregnancy may cause the
      increase in coagulation factors and ultimately the prothrombotic state
      characteristic of pregnancy. CONCLUSIONS: Since no differences were apparent
      between the different phases of pregnancy it suggests that activation of the
      coagulation system commences with pregnancy and this pro-thrombotic state
      continues till at least 8 weeks after birth. These results may shed light on
      possible pathological mechanisms employed in the development of abnormal or
      ailing pregnancy.

PMID- 24861477
TI  - Intranasal immunization with live recombinant Lactococcus lactis combined with
      heat-labile toxin B subunit protects chickens from highly pathogenic avian
      influenza H5N1 virus.
AB  - Development of safe and effective vaccines to prevent highly pathogenic avian
      influenza H5N1 virus infection is a challenging goal. Lactococcus lactis (L.
      lactis) is an ideal delivery vector for vaccine development, and it has been
      shown previously that oral immunization of encapsulated secretory L. lactis
      hemagglutinin (HA) could provide complete protection against homologous H5N1
      virus challenge in the mice model. While intranasal immunization is an appealing
      approach, it is now reported that secretory L. lactis-HA combined with mucosal
      adjuvant heat-labile toxin B subunit (LTB) could provide protective immunity in
      the chicken model. As compared to intranasal immunization with L. lactis-HA
      alone, L. lactis-HA combined with LTB (L. lactis-HA + LTB) could elicit robust
      neutralizing antibody responses and mucosal IgA responses, as well as strong
      cellular immune responses in the vaccinated chickens. Importantly, intranasal
      immunization with L. lactis-HA + LTB could provide 100% protection against H5N1
      virus challenge. Taken together, these results suggest that intranasal
      immunization with L. lactis-HA + LTB can be considered as an effective approach
      for preventing and controlling infection of H5N1 virus in poultry during an avian
      influenza A/H5N1 pandemic.

PMID- 24861479
TI  - Fatigue, psychological and cognitive impairment following transient ischaemic
      attack and minor stroke: a systematic review.
AB  - Transient ischaemic attack (TIA) and minor stroke are characterized by short
      lasting symptoms; however, anecdotal and empirical evidence suggests that these
      patients experience ongoing cognitive/psychological impairment for which they are
      not routinely treated. The aims were (i) to investigate the prevalence and time
      course of fatigue, anxiety, depression, post-traumatic stress disorder(PTSD) and
      cognitive impairment following TIA/minor stroke; (ii) to explore the impact on
      quality of life (QoL), change in emotions and return to work; and (iii) to
      identify where further research is required and potentially inform an
      intervention study. A systematic review of MEDLINE, EMBASE, PSYCINFO, CINAHL, the
      Cochrane libraries and the grey literature between January 1993 and April 2013
      was undertaken. Literature was screened and data were extracted by two
      independent reviewers. Studies were included of adult TIA/minor stroke
      participants with any of the outcomes of interest: fatigue, anxiety, depression,
      PTSD, cognitive impairment, QoL, change in emotions and return to work. Random
      effects meta-analysis pooled outcomes by measurement tool. Searches identified
      5976 records, 289 were assessed for eligibility and 31 studies were included.
      Results suggest high levels of cognitive impairment and depression post-TIA/minor
      stroke which decreased over time. However, frequencies varied between studies.
      Limited information was available on anxiety, PTSD and fatigue. Meta-analysis
      revealed that the measurement tool administered influenced the prevalence of
      cognitive impairment: Mini-Mental State Examination 17% [95% confidence interval
      (CI) 7, 26]; neuropsychological test battery 39% (95% CI 28, 50); Montreal
      Cognitive Assessment 54% (95% CI 43, 66). There is evidence to suggest that
      TIA/minor stroke patients may experience residual impairments; however, results
      should be interpreted with caution because of the few high quality studies.
      Notwithstanding, it is important to raise awareness of potential subtle but
      meaningful residual impairments. 

PMID- 24861480
TI  - Factors affecting outcome of allogeneic stem cell transplantation as salvage in
      patients with acute myeloid leukemia primary refractory to intensive induction
      therapy.

PMID- 24861481
TI  - Breast conserving therapy for DCIS--does size matter?
AB  - The incidence of ductal carcinoma in situ has increased dramatically with the use
      of screening mammography. Most patients can be considered for breast conserving
      therapy, depending upon patient and pathologic variables. In addition to other
      factors, tumor size is important to provide proper patient selection for breast
      conserving surgery and predict risk of local recurrence.

PMID- 24861482
TI  - 'The fault, dear Brutus, is not in our stars, But in ourselves'. Reflections on
      Nursing must be a graduate profession (Well he would say that wouldn't he!).

PMID- 24861483
TI  - Using sound for microbial eradication--light at the end of the tunnel?
AB  - Sonodynamic antimicrobial chemotherapy (SACT) is a novel modality, which uses
      ultrasound to kill bacteria by the activation of molecules termed sonosensitisers
      (SS) to produce reactive oxygen species that are toxic to microorganism although
      microbial resistance to this modality has been reported. There are a growing
      number of SS being reported with the dual ability to be activated by both
      ultrasound and light, and we hypothesis that a novel antimicrobial strategy,
      potentially known as sonophotodynamic antimicrobial chemotherapy (SPACT), could
      be developed based on these agents. SPACT offers advantages over SACT and could
      constitute a new weapon in the fight against the growing global threat posed by
      microbial infections.

PMID- 24861484
TI  - Serum YKL-40 and uterine artery Doppler -- a prospective cohort study, with focus
      on preeclampsia and small-for-gestational-age.
AB  - OBJECTIVE: To test if serum YKL-40 is increased in women developing preeclampsia
      or small-for-gestational age fetuses. We also assessed the association between
      uterine artery pulsatility index, notching and serum YKL-40 levels. DESIGN:
      Prospective cohort study. SETTING: A primary referral unit for obstetric
      ultrasound. POPULATION: A total of 1214 unselected pregnant women enrolled at
      nuchal translucency examination between 11(+3) and 13(+6)  weeks of gestation.
      METHODS: All women had ultrasound and blood sample collection at the nuchal
      translucency scan, a 20-week malformation scan and 25-week and 32-week fetal
      growth examinations. Uterine artery Doppler was assessed and outcome was
      registered from medical records. MAIN OUTCOME MEASURES: Preeclampsia,
      hypertension, small-for-gestational age. RESULTS: Serum YKL-40 was associated
      with increasing maternal age (p < 0.0001), body mass index (p = 0.0002),
      primiparity (p = 0.0003), and hypertension (p = 0.015). Serum YKL-40 increased
      from 12 to 20 weeks and decreased from 20-25 and 25-32 weeks of gestation. No
      association was found between preeclampsia and serum YKL-40. Small-for
      gestational-age at birth was significantly associated with a 5.4% increase in
      serum YKL-40 at 32 weeks of gestation (95% CI 1.5-9.3, p = 0.005). An association
      was found between uterine artery pulsatility index at 32 weeks and small-for
      gestational age (p = 0.0015) but not between YKL-40 and uterine artery notching
      (p = 0.83). CONCLUSIONS: Serum YKL-40 was not associated with preeclampsia.
      Increasing serum YKL-40 was related to maternal age, body mass index and small
      for-gestational age and may reflect an exaggerated inflammatory response.

PMID- 24861486
TI  - Extensive human suffering: a point prevalence survey of patients' most
      distressing concerns during inpatient care.
AB  - AIM: To explore patients' most distressing concerns during a hospital stay.
      BACKGROUND: The characteristics of hospitalised patients have changed. Care is
      provided at a higher age, lengths of stay have fallen and the nursing workload is
      increasing. It is presumed that hospitalised patients are more seriously ill and
      have more palliative needs than previously. Studies show that inpatients suffer
      from more distress than similar outpatients although there is a lack of overall
      knowledge about inpatients' distress and major concerns, regardless of age,
      diagnosis or care setting. METHODS: This study was part of a point prevalence
      survey (PPS) concerning symptom prevalence. Of the 710 patients who participated
      in the PPS, 678 (95%) answered an open-ended question in a questionnaire: What is
      your main concern or what is most distressing or troublesome for you at present?
      Using a life-world approach, the text was analysed qualitatively and patients'
      concerns were interpreted in two main dimensions, an intersubjective dimension
      and a temporal dimension. FINDINGS: The patients reported extensive suffering due
      to illness, symptoms and failing health. Patients were concerned about family
      members, existential issues and the future. Three aspects of the patients' most
      distressing concerns were interpreted: The suffering self, The suffering person
      in close relations and The suffering person in a threatening world. CONCLUSION:
      Hospitalised patients are affected by severe illness, distressing symptoms and
      existential quandaries, revealing extensive human suffering in the midst of the
      demanding activities that take place during an ordinary day in a hospital. To
      support patients and alleviate suffering, hospital staff need to be more
      sensitive to patients' most distressing concerns. This presupposes a hospital
      environment in which the value system supports caring and comforting behaviour.

PMID- 24861485
TI  - Aberrant promoter methylation of PPP1R3C and EFHD1 in plasma of colorectal cancer
      patients.
AB  - Aberrant DNA methylation is a common epigenetic alteration involved in colorectal
      cancer (CRC). In our previous study, we performed methylated DNA
      immunoprecipitation-on-chip analysis combined with gene re-expression analysis by
      5-aza-2'-deoxycytidine treatment, to identify methylation genes in CRC genome
      widely. Among these genes, 12 genes showed aberrant hypermethylation frequently
      in >75% of 149 CRC samples but did not in normal samples. In this study, we aim
      to find out any of these methylation genes to be utilized for CRC detection using
      plasma DNA samples. Primers for methylation-specific PCR and pyrosequencing were
      designed for seven of the 12 genes. Among them, PPP1R3C and EFHD1 were rarely
      hypermethylated in peripheral blood cells, but frequently hypermethylated in 24
      CRC tissue samples and their corresponding plasma samples. In plasma samples,
      PPP1R3C was methylated in 81% (97/120) of CRC patients, but only in 19% (18/96)
      of noncancer patients (P = 6 * 10(-20) , Fisher's exact test). In combined
      analysis with EFHD1, both genes were methylated in 53% (64/120) of CRC patients,
      but only in 4% (4/96) of noncancer patients (P = 2 * 10(-16) ), giving high
      specificity of 96%. At least one of the two genes was methylated in 90% (108/120)
      of CRC patients, and 36% (35/96) of control patients, giving high sensitivity of
      90%. Compared with low sensitivity of carcinoembryonic antigen (17% at stage I,
      40% at stage II) and CA19-9 (0% at stage I, 13% at stage II) for early-stage
      CRCs, sensitivity of aberrant methylation was significantly higher: PPP1R3C
      methylation at 92% (11/12) for stage I and 77% (23/30) for stage II, and
      methylation of at least one gene at 100% (12/12) for stage I and 87% (26/30) for
      stage II. PPP1R3C methylation or its combined use of EFHD1 methylation was highly
      positive in CRC plasma samples, and they might be useful in detection of CRC,
      especially for early-stage CRCs. 

PMID- 24861487
TI  - Prevention of early-onset Group B Streptococcal disease - the Northern Ireland
      experience.
AB  - OBJECTIVES: To ascertain guideline adherence for prevention of Group B
      Streptococcal (GBS) neonatal infection and establish prevalence and outcomes in
      Northern Ireland (NI). DESIGN: Retrospective observational study. SETTING:
      Northern Ireland maternity units. POPULATION: Using NI Health Information Systems
      the following were identified: (1) a cohort of women with one or more risk
      factors for GBS disease in 2009-2010, (2) all culture-positive cases of GBS in
      babies aged 0-89 days (2008-2010), (3) stillbirths due to GBS (2009-2010).
      METHODS: Information was analysed for a 15% randomised sample of the available
      cases. Maternal and infant case notes were reviewed for confirmed cases of
      neonatal early onset GBS (EOGBS) during 2008-2010. MAIN OUTCOME MEASURES:
      Adherence to the 2003 RCOG guideline on prevention of GBS disease (2009-2010).
      Number of neonatal GBS infections: antenatal risk factors, management and
      neonatal outcomes (2008-2010). The number of stillbirths related to GBS (2009
      2010). RESULTS: Five hundred and seventy-four women had one or more identifiable
      risk factors for GBS disease; intrapartum antibiotic prophylaxis (IAP) was
      administered in 42% of cases. Improved administration of IAP was noted in the
      presence of escalating risk factors. At best, guideline adherence was 50-70%.
      Forty-three neonates had proven early-onset Group B Streptococcal disease; 55.8%
      had maternal risk factors. Of the total identified cases, 25.5% received IAP. The
      total mortality rate was 11.46%. The incidence of EOGBS disease in NI was
      0.57/1000 live births. CONCLUSIONS: Prevalence of EOGBS is higher in NI than the
      UK as a whole. Risk factors are present in 55.8% of mothers; IAP does not prevent
      all cases of EOGBS.

PMID- 24861488
TI  - Spectrally selective chiral silicon metasurfaces based on infrared Fano
      resonances.
AB  - Metamaterials and metasurfaces represent a remarkably versatile platform for
      light manipulation, biological and chemical sensing, and nonlinear optics. Many
      of these applications rely on the resonant nature of metamaterials, which is the
      basis for extreme spectrally selective concentration of optical energy in the
      near field. In addition, metamaterial-based optical devices lend themselves to
      considerable miniaturization because of their subwavelength features. This
      additional advantage sets metamaterials apart from their predecessors, photonic
      crystals, which achieve spectral selectivity through their long-range
      periodicity. Unfortunately, spectral selectivity of the overwhelming majority of
      metamaterials that are made of metals is severely limited by high plasmonic
      losses. Here we propose and demonstrate Fano-resonant all-dielectric metasurfaces
      supporting optical resonances with quality factors Q>100 that are based on CMOS
      compatible materials: silicon and its oxide. We also demonstrate that these
      infrared metasurfaces exhibit extreme planar chirality, opening exciting
      possibilities for efficient ultrathin circular polarizers and narrow-band thermal
      emitters of circularly polarized radiation. 

PMID- 24861489
TI  - Synthesis of 5- and 8-deoxytetrodotoxin.
AB  - Tetrodotoxin, a toxic principle of puffer fish intoxication, is one of the most
      famous marine natural products owing to its complex structure and potent
      biological activity, which leads to fatal poisoning. Continuous synthetic studies
      on tetrodotoxin and its analogues to elucidate biologically interesting issues
      associated with tetrodotoxin have led to the development of versatile routes for
      a variety of tetrodotoxin derivatives. With the aim of investigating the
      structure-activity relationship of tetrodotoxin with voltage-gated sodium
      channels, this study describes the first total syntheses of 5-deoxytetrodotoxin,
      a natural analogue of tetrodotoxin, and 8-deoxytetrodotoxin, an unnatural
      analogue, from a newly designed, versatile intermediate in an efficient manner.
      An estimation of the biological activities of these compounds reveals the
      importance of the hydroxy groups at the C-5 and C-8 positions on the inhibition
      of voltage-gated sodium channels. 

PMID- 24861490
TI  - Factors associated with returning to football after anterior cruciate ligament
      reconstruction.
AB  - PURPOSE: The aim of the present investigation was to identify possible factors
      associated with returning to football on an average 3.2 +/- 1.4 years after
      anterior cruciate ligament (ACL) reconstruction in both male and female football
      players. METHODS: The players were recruited from a patient database of football
      players that have undergone an ACL reconstruction between 2004 and 2007 at the
      Capio Artro Clinic, Sophiahemmet in Stockholm, Sweden. Special attention was paid
      to gender, age, type of graft for ACL reconstruction, associated injuries,
      anterior knee laxity, thigh muscle torques and symptoms/problems during, and/or
      after physical activity. In the beginning of the summer of 2009, 205 players
      (37.9 %) out of 541 players filled out a questionnaire designed to evaluate
      physical activity and knee function in a sports-specific setting. A detailed
      dropout analysis showed that females responded to a higher degree than males. No
      other significant differences between responders and non-responders were found.
      RESULTS: Fifty-four per cent (n = 111) had returned to football, and 46 % (n =
      94) had not. Using logistic regression analyses, we found that the female gender
      (p = 0.036, OR 0.518), cartilage injury (p = 0.013, OR 0.368), and pain during
      physical activity (p = 0.002, OR 0.619) were significant negative predictors for
      returning to football after ACL reconstruction and rehabilitation. For players
      with all three significant factors, only 10 % returned to football compared to
      76.5 % of those without any of these factors. CONCLUSIONS: Female gender,
      cartilage injury, and knee pain during physical activity were independent
      negative predictors for returning to football after ACL reconstruction. At a mean
      follow-up of 3.2 +/- 1.4 years after ACL reconstruction, pain during physical
      activity was reported to be the most common symptom/problem in football players.
      The clinical relevance of this study is to improve the treatment of ACL injured
      football players focusing on female gender and knee pain. Furthermore, ACL injury
      prevention should be highlighted in football players, especially female players.

PMID- 24861492
TI  - Daylight photodynamic therapy with methyl aminolevulinate cream as a convenient,
      similarly effective, nearly painless alternative to conventional photodynamic
      therapy in actinic keratosis treatment: a randomized controlled trial.
AB  - BACKGROUND: Daylight photodynamic therapy (DL-PDT) of actinic keratosis (AK) has
      shown preliminary efficacy and safety results comparable to conventional
      photodynamic therapy (c-PDT), using methyl aminolevulinate (MAL) cream.
      OBJECTIVES: To demonstrate the efficacy and safety of DL-PDT vs. c-PDT in
      treating mild facial/scalp AK. MATERIALS AND METHODS: This 24-week randomized,
      controlled, investigator-blinded, multicentre, intra-individual efficacy (non
      inferiority) and safety (superiority regarding pain) study enrolled 100 subjects.
      AKs on the face/scalp were treated once, with DL-PDT on one side and c-PDT on the
      contralateral side. Primary end points for DL-PDT at week 12 were efficacy [non
      inferiority regarding complete lesion response (mild AK)] and safety (superiority
      regarding subject's assessment of pain). Lesions with complete response 12 weeks
      after one treatment session were followed until week 24. The safety evaluation
      included incidence of adverse events. Subject satisfaction was classified using a
      questionnaire. RESULTS: At week 12, the complete lesion response rate with DL-PDT
      was non-inferior to c-PDT (89.2% vs. 92.8%, respectively; 95% confidence interval
      -6.8 to -0.3), confirmed by intention-to-treat analysis. Additionally, regardless
      of the treatment used, 96% of mild lesions were maintained in complete response
      24 weeks after the PDT session. For DL-PDT, subject-reported pain was
      significantly lower (0.8 vs. 5.7, respectively; P < 0.001), with better
      tolerability and significantly higher subject satisfaction regarding convenience
      and outcome. CONCLUSIONS: Daylight-mediated PDT was not inferior in efficacy to
      Metvix c-PDT (mild AK response rate), better tolerated, nearly painless and more
      convenient for patients.

PMID- 24861493
TI  - Access to 1,2-dihydroisoquinolines through gold-catalyzed formal [4+2]
      cycloaddition.
AB  - A new synthetic route to the privileged 1,2-dihydroisoquinolines is reported.
      This method, which relies on a gold-catalyzed formal [4+2] cycloaddition between
      ynamides and imines, provides a new retrosynthetic disconnection of the 1,2
      dihydroisoquinoline core by installing the 1,8a C-C and 2,3 C-N bonds in one
      step. Both aldimines and ketimines can be used as substrates. In addition, one
      example of dihydrofuropyridine synthesis is also demonstrated.

PMID- 24861491
TI  - Pathogenetic mechanisms of focal cortical dysplasia.
AB  - Focal cortical dysplasias (FCDs) constitute a prevalent cause of intractable
      epilepsy in children, and is one of the leading conditions requiring epilepsy
      surgery. Despite recent advances in the cellular and molecular biology of these
      conditions, the pathogenetic mechanisms of FCDs remain largely unknown. The
      purpose if this work is to review the molecular underpinnings of FCDs and to
      highlight potential therapeutic targets. A systematic review of the literature
      regarding the histologic, molecular, and electrophysiologic aspects of FCDs was
      conducted. Disruption of the mammalian target of rapamycin (mTOR) signaling
      comprises a common pathway underlying the structural and electrical disturbances
      of some FCDs. Other mechanisms such as viral infections, prematurity, head
      trauma, and brain tumors are also posited. mTOR inhibitors (i.e., rapamycin) have
      shown positive results on seizure management in animal models and in a small
      cohort of patients with FCD. Encouraging progress has been achieved on the
      molecular and electrophysiologic basis of constitutive cells in the dysplastic
      tissue. Despite the promising results of mTOR inhibitors, large-scale randomized
      trials are in need to evaluate their efficacy and side effects, along with
      additional mechanistic studies for the development of novel, molecular-based
      diagnostic and therapeutic approaches.

PMID- 24861494
TI  - Preexisting dual antiplatelet treatment increases the risk of post-thrombolysis
      intracranial hemorrhage in Chinese stroke patients.
AB  - OBJECTIVE: Previous studies have shown conflicting results on the use of
      antiplatelet (AP) agent and its risk of symptomatic intracerebral hemorrhage
      (sICH) following thrombolysis for acute ischemic stroke. Our study was to explore
      the safety of intravenous (IV) thrombolysis in Chinese stroke patients who were
      on AP prior to stroke. METHODS: Data were collected from the thrombolysis
      implementation and monitor of acute ischemic stroke in China (TIMS-China)
      registry. Symptomatic ICH defined per SITS-MOST (safe implementation of
      treatments in stroke-monitoring study), ECASS II (second European-Australasian
      acute stroke study), and NINDS (National Institute of Neurological Disorders and
      Stroke) criteria, 90-day functional outcome, and 7-day and 90-day mortalities
      were compared between the stroke patients who were on mono and dual AP therapy.
      RESULTS: A total of 157 (14.2%) patients received at least one AP drug within 24
      hours before thrombolysis. Patients with preexisting dual AP treatment had higher
      rate of sICH (14.3% (2/14) per SITS-MOST, 21.4% (3/14) per ECASS II definitions)
      than those on no AP treatment. No significant difference was found in the rate of
      sICH or 7-day or 90-day mortalities between the groups on aspirin (ASA) alone and
      on no AP treatment. DISCUSSION: The risk of developing sICH is low when
      thrombolysis is given to patients who are on ASA alone. However, there is
      potential increased risk of sICH if a patient is on dual AP treatment.

PMID- 24861495
TI  - Inhibitor effect of dexketoprofen in rat model of pentylenetetrazol-induced
      seizures.
AB  - OBJECTIVES: The relationship between epilepsy and inflammation is known, and it
      has been reported that there is an increase in cyclooxygenase (COX) levels in
      epilepsy. We aim to reveal the anticonvulsant effects of dexketoprofen in
      pentylenetetrazol (PTZ)-induced seizures in rats. MATERIALS AND METHODS: Forty
      eight male Sprague-Dawley rats, 24 of them for EEG recording and 24 of them are
      for behavioral studies, were randomly divided in two groups: Group A for EEG
      recordings and Group B for behavioral assessment. A weight of 70 mg/kg PTZ was
      used for behavioral studies after dexketoprofen administration. Thirty-five
      milligrams per kilogram PTZ were used for EEG recording after dexketoprofen
      administration. The electrodes were implanted on dura over the left frontal
      cortex and the reference electrode was implanted over the cerebellum for EEG
      recording. The Racine convulsion scale (RCS), first myoclonic jerk (FMJ) onset
      time, and spike percentages were evaluated between the two groups. RESULTS: There
      was a significant (P< 0.05) difference between the RCS, FMJ onset time (P<
      0.001), and spike percentage (P< 0.05) between the groups (Group 2 compared with
      Groups 3 and 4). CONCLUSION: Dexketoprofen has an antiepileptic feature and this
      effect increases as the dosage increases, however it is currently unknown through
      which mechanism this drug shows its anticonvulsant effect. Dexketoprofen, in the
      group of NSAIDs, shows an anticonvulsant effect on PTZ-induced epilepsy model.
      This study suggests that dexketoprofen can preferably be used with NSAIDs for
      epileptic patients in clinical practice.

PMID- 24861496
TI  - Effects of mobile phone radiation (900 MHz radiofrequency) on structure and
      functions of rat brain.
AB  - OBJECTIVES: The goals of this study were: (1) to obtain basic information about
      the effects of long-term use of mobile phones on cytological makeup of the
      hippocampus in rat brains (2) to evaluate the effects on antioxidant status, and
      (3) to evaluate the effects on cognitive behavior particularly on learning and
      memory. METHODS: Rats (age 30 days, 120 +/- 5 g) were exposed to 900 MHz radio
      waves by means of a mobile hand set for 4 hours per day for 15 days. Effects on
      anxiety, spatial learning, and memory were studied using the open field test, the
      elevated plus maze, the Morris water maze (MWM), and the classic maze test.
      Effects on brain antioxidant status were also studied. Cresyl violet staining was
      done to assess the neuronal damage. RESULT: A significant change in behavior,
      i.e., more anxiety and poor learning was shown by test animals as compared to
      controls and sham group. A significant change in the level of antioxidant enzymes
      and non-enzymatic antioxidants, and an increase in lipid peroxidation were
      observed in the test rats. Histological examination showed neurodegenerative
      cells in hippocampal sub regions and the cerebral cortex. DISCUSSION: Thus our
      findings indicate extensive neurodegeneration on exposure to radio waves.
      Increased production of reactive oxygen species due to exhaustion of enzymatic
      and non-enzymatic antioxidants and increased lipid peroxidation indicate
      extensive neurodegeneration in selective areas of CA1, CA3, DG, and the cerebral
      cortex. This extensive neuronal damage results in alterations in behavior related
      to memory and learning.

PMID- 24861498
TI  - Characteristics of patients with non-variceal upper gastrointestinal bleeding
      taking antithrombotic agents.
AB  - BACKGROUND AND AIM: The present study aimed to clarify the features and
      management of non-variceal upper gastrointestinal bleeding (UGIB) in Japanese
      patients taking antithrombotic agents. METHODS: We retrospectively investigated
      the medical records of 560 patients who underwent emergency endoscopy for UGIB
      from 2002 to 2013. The patients were divided into two groups: group A,
      antithrombotic agent use; and group NA, no antithrombotic agent use. We compared
      clinical characteristics, comorbidities, and causes of UGIB between the groups.
      We also investigated management with antithrombotics. RESULTS: Of 560 patients
      with UGIB, 27.5% were taking antithrombotics, and this proportion gradually
      increased during the study period. Mean hemoglobin levels on admission were
      significantly lower in group A (8.0 +/- 1.7 g/dL) than in group NA (8.9 +/- 2.9
      g/dL) (P < 0.001). Patients in group A developed more gastric ulcers and multiple
      ulcers than did patients in group NA. Incidence of Forrest Ia-type bleeding was
      lower in group A than in group NA (P < 0.001), and the rate of endoscopic
      hemostasis was significantly higher in group A (98.7%) than in group NA (94.3%)
      (P = 0.022). After the release of the 2012 Japan Gastroenterological Endoscopy
      Society guidelines, the antithrombotic agent cessation periods were significantly
      shortened (P < 0.001). CONCLUSIONS: Among patients with UGIB, those taking
      antithrombotics exhibited more severe clinical signs. However spurting hemorrhage
      was rare. Antithrombotics may be resumed early after endoscopic hemostasis.

PMID- 24861497
TI  - A cooperative jack model of random coil-to-elongation transition of the FH1
      domain by profilin binding explains formin motor behavior in actin
      polymerization.
AB  - Filopodia are essential for the development of neuronal growth cones, cell
      polarity and cell migration. Their protrusions are powered by the polymerization
      of actin filaments linked to the plasma membrane, catalyzed by formin proteins.
      The acceleration of polymerization depends on the number of profilin-actins
      binding with the formin-FH1 domain. Biophysical characterization of the
      disordered formin-FH1 domain remains a challenge. We analyzed the conformational
      distribution of the diaphanous-related formin mDia1-FH1 bound with one to six
      profilins. We found a coil-to-elongation transition in the FH1 domain. We propose
      a cooperative "jack" model for the Formin-Homology-1 (FH1) domain of formins
      stacked by profilin-actins. 

PMID- 24861500
TI  - Valence to core X-ray emission spectroscopy.
AB  - This Progress Report discusses the chemical sensitivity of Kbeta valence to core
      X-ray emission spectroscopy (vtc-XES) and its applications for investigating 3d
      transition-metal based materials. Vtc-XES can be used for ligand identification
      and for the characterization of the valence electronic levels. The technique
      provides information that is similar to valence band photoemission spectroscopy
      but the sample environment can be chosen freely and thus allows measurements in
      presence of gases and liquids and it can be applied for measurements under in
      situ/operando or extreme conditions. The theoretical basis of the technique is
      presented using a one-electron approach and the vtc-XES spectral features are
      interpreted using ground state density functional theory calculations. Some
      recent results obtained by vtc-XES in various scientific fields are discussed to
      demonstrate the potential and future applications of this technique. Resonant X
      ray emission spectroscopy is briefly introduced with some applications for the
      study of 3d and 5d-transition-metal based systems. 

PMID- 24861499
TI  - Controlling interfacial recombination in aqueous dye-sensitized solar cells by
      octadecyltrichlorosilane surface treatment.
AB  - A general and convenient strategy is proposed for enhancing photovoltaic
      performance of aqueous dye-sensitized solar cells (DSCs) through the surface
      modification of titania using an organic alkyl silane. Introduction of
      octadecyltrichlorosilane on the surface of dyed titania photoanode as an organic
      barrier layer leads to the efficient suppression of electron recombination with
      oxidized cobalt species by restricting access of the cobalt redox couple to the
      titania surface. The champion ODTS-treated aqueous DSCs (0.25 mM ODTS in hexane
      for 5 min) exhibit a V(oc) of 821+/-4 mV and J(sc) of 10.17+/-0.21 mA cm(-2),
      yielding a record PCE of 5.64+/-0.10%. This surface treatment thus serves as a
      promising post-dye strategy for improving the photovoltaic performance of other
      aqueous DSCs.

PMID- 24861501
TI  - Facilitation of action planning in children with autism: the contribution of the
      maternal body odor.
AB  - Imitation is a key socio-cognitive skill impaired in individuals with Autism
      Spectrum Conditions (ASC). It is known that the familiarity with an actor
      facilitates the appearance of imitative abilities. Here, we explore whether a
      highly familiar and socially relevant stimulus presented in the olfactory
      modality is able to improve spontaneous imitation as early as at the level of
      action planning. A group of 20 children with ASC and 20 controls observed their
      own mother or the mother of another child performing a reach-to-grasp action
      towards an object, under the exposure to their maternal odor, the odor of the
      mother of another child or no odor. Subsequently, children acted upon the same
      object with no specific instruction to imitate. Child's movement initiation time
      (MIT) served as an indicator of motor planning facilitation induced by action
      observation. Results suggest that for children with ASC (but not controls) MIT
      was significantly lower when exposed to the maternal odor both when interacting
      with a familiar or an unfamiliar model. In the former case, the performance is
      comparable to controls. The familiar model in the absence of any olfactory cue is
      able to induce a facilitation effect, but the maximal facilitation on MIT is
      evident when maternal odor and familiar model are paired. We hypothesize that for
      children with ASC the maternal odor provides relevant social motivation for
      taking advantage of others' actions when planning movements in an imitative
      context. 

PMID- 24861502
TI  - [Cardiovascular effects of beta1 and beta3-adrenergic receptor autoantibodies in
      Lewis rat].
AB  - PURPOSE: To analyze vascular reactivity changes in response to immunization
      protocols with antigens corresponding to the second extracellular loop of -beta3
      and -beta1 and 3 adrenergic receptors (AR). METHODS: Lewis rats were immunized
      for 3months with peptidic sequences corresponding to the second extracellular
      loop of beta3-AR or beta1 and 3-AR. Specific beta3-AR antibodies were
      characterized by Elisa and purified using "Proteus Protein G" kit. Their
      functionality were tested in rabbit isolated ventricular cardiomyocytes. Aortic
      and mesenteric artery rings isolated from control or immunized rats were mounted
      in organ baths and precontracted with phenylephrine. Then, relaxant curves were
      established. RESULTS: SR58611A (10nM), a preferential beta3-AR agonist and
      purified beta3-AR antibodies (25MUg/mL) induced a decrease of cell shortening (
      39.56+/-4.4% [n=11] and -18.45+/-3.9% [n=10] respectively) in isolated
      cardiomyocytes. This decrease was significantly inhibited when the cardiomyocytes
      were pre-incubated with the L-748337 (1MUM), a selective beta3-AR antagonist
      (P<0.05). In contrast with what was observed in rats immunized against the beta1
      AR, vasorelaxations induced by acetylcholine and SR58611A in both aorta and
      mesenteric arteries were unaltered in rats immunized against the beta3-AR and
      beta1 and 3-AR. CONCLUSION: These results show, for the first time, that beta3-AR
      antibodies induced a beta3-AR agonist-like activity. They would not have a
      vascular pathogenic action but would offset the endothelial dysfunction caused by
      beta1-AR antibodies.

PMID- 24861504
TI  - Focus on mTOR inhibitors and tacrolimus in renal transplantation:
      pharmacokinetics, exposure-response relationships, and clinical outcomes.
AB  - Mammalian target of rapamycin (mTOR)-inhibitor-containing immunosuppressive
      regimens have been developed as part of calcineurin inhibitor (CNI)
      minimization/withdrawal strategies for renal transplant recipients, with the goal
      of avoiding CNI-associated nephrotoxicity. This review focuses on the
      pharmacokinetic interactions and exposure-response relationships of mTOR
      inhibitors and tacrolimus (TAC), the most widely used CNI. We also discuss key
      randomized clinical studies that have evaluated use of this combination in renal
      transplantation. Pharmacokinetic studies have shown that mTOR inhibitors,
      everolimus (EVR) and sirolimus (SRL), have a large intra- and inter-patient
      variability in drug exposure, and narrow therapeutic windows (trough levels [C0]
      3-8 ng/mL and 5-15 ng/mL, respectively). Consequently, routine therapeutic drug
      monitoring of EVR and SRL is recommended to optimize efficacy and minimize
      toxicity in individual patients. As there is a good correlation between C0 and
      area under the curve (AUC), C0 can be used as a convenient and reliable measure
      of mTOR drug exposure. Clinical data on the use of EVR or SRL in TAC minimization
      strategies in renal transplantation are limited. Available evidence suggests that
      treatment with EVR allows early and substantial TAC minimization when used with
      basiliximab induction and corticosteroids, to achieve good renal function without
      compromising efficacy or safety. However, data comparing this combination with
      other regimens are lacking. Results with SRL are more mixed. SRL in combination
      with reduced TAC has been shown to provide less nephrotoxicity than the
      SRL/standard TAC combination, with comparable efficacy and safety. However, this
      approach has been shown to be inferior to other regimens in terms of
      patient/graft survival and biopsy-proven acute rejection (vs MMF/TAC) as well as
      renal function (vs MMF/TAC and SRL/MMF). Further studies are needed to define the
      therapeutic window for TAC when used in combination with mTOR inhibitors,
      evaluate EVR/reduced TAC versus other regimens, assess long-term outcomes, and
      determine efficacy and safety in high-risk patients.

PMID- 24861503
TI  - Safety and effectiveness of the association ezetimibe-statin (E-S) versus high
      dose rosuvastatin after acute coronary syndrome: the SAFE-ES study.
AB  - BACKGROUND: Statin therapy is a cornerstone therapy for secondary prevention
      after acute coronary syndrome (ACS). However, the use of these drugs can be
      limited by side effects, mainly muscular pain. Ezetimibe is a newer lipid
      lowering agent, with fewer side effects. AIMS: The present study was designed to
      compare a commercially available association of ezetimibe and simvastatin (E-S)
      to high dose Rosuvastatin on cholesterol and muscular enzyme levels and
      occurrence of muscular pain. METHODS: All consecutive ACS statin-naive patients
      with LDL cholesterol (LDL-C)>100mg/dL randomly received either high dose statin
      (Rosuvastatin 20mg) or E-S 10/40-mg. All patients had one-month follow-up with
      biological testing and clinical examination. We compared the two groups on the
      biological efficiency and incidence of muscular pain. RESULTS: One hundred and
      twenty-eight patients were randomized; 64 received E-S and 64 Rosuvastatin. In
      the two groups, the lowering of LDL-C level (Delta=51%) at one month was
      significant (P<0.01) without any difference in the rate of lowering on LDL-C or
      HDL-C suggesting that E-S is as effective as high dose Rosuvastatin (P=0.77 and
      P=0.99). The rate of patients reaching the objective of LDL-C<100mg/dL (45%) and
      LDL-C<70mg/dL (51%) was not different in the two clusters (P=0.65). Incidence of
      muscular pain was 15% higher in patients treated with Rosuvastatin (P=0.01)
      without any difference on CPK level (P=0.6). CONCLUSION: Using an association of
      E-S in an effective alternative strategy to high dose Rosuvastatin with a lower
      incidence of muscular pain, which might impact adherence to medication after ACS.

PMID- 24861505
TI  - The molecular evidence of neural plasticity induced by cerebellar repetitive
      transcranial magnetic stimulation in the rat brain: a preliminary report.
AB  - Cerebellar repetitive transcranial magnetic stimulation (rTMS) has been applied
      to treat several pathological conditions with insufficient evidence of molecular
      mechanism. Neural plasticity is proposed as one of mechanism. This study aimed to
      (1) confirm the feasibility of focal stimulation over cerebellar cortex and (2)
      investigate cerebellar rTMS effects on molecular changes associated with neural
      plasticity in the rat. For feasibility, six male Sprague-Dawley rats underwent
      (18)F-FDG positron emission tomography (PET) to confirm focal stimulation on the
      cerebellar cortex after rTMS. For molecular evidence, thirty rats underwent a
      single (N=15) or 10 sessions (N=15) of rTMS with low-, high-frequency, or sham
      stimulation. In cerebellar cortex, reverse-transcriptase polymerase chain
      reaction and western blotting were performed on mRNA and proteins associated with
      neural plasticity: metabotrophic glutamate receptor 1 (GluR1), 2-amino-5-methyl-4
      isoxazole-propionatic acid (AMPA) receptor (GluR2) and protein kinase C (PKC). As
      a result, (18)F-FDG-PET showed an increase of glucose metabolism in the
      cerebellar cortex. The transcription of mGluR1 decreased following a single
      session of high-frequency rTMS. Synthesis of mGluR, PKC and GluR2 was reduced
      after rTMS, especially high frequency stimulation. It is suggested that rTMS
      could focus on the cerebellar cortex in the rat and induce neural plasticity
      associated with long-term depression. 

PMID- 24861506
TI  - Platelet-derived nerve growth factor supports the survival of cholinergic neurons
      in organotypic rat brain slices.
AB  - Platelets play a role in repair of vessels and contain different growth factors,
      including nerve growth factor (NGF). Since NGF is the most potent growth factor
      to support survival of cholinergic neurons, we aimed to study the effects of
      platelet-derived NGF on cholinergic neurons in organotypic brain slices. Brain
      slices of the nucleus basalis of Meynert (nBM) were cultured with or without NGF
      (10ng/ml) or platelet extracts (100MUg/ml) or fresh platelets (10(8)
      platelets/ml). In order to enhance NGF in platelets recombinant NGF (100ng) was
      loaded into platelets using ultrasound (3h). Our data show that recombinant NGF
      markedly supports survival of cholinergic neurons. The addition of fresh
      platelets showed a tendency for enhancing cholinergic neuron numbers, while
      platelet extracts had no effects. Ultrasound was highly effective to load
      recombinant NGF into platelets. The addition of NGF-loaded platelets markedly
      enhanced cholinergic neuron numbers. In conclusion, our data provide evidence
      that NGF-derived platelets may counteract cell death of cholinergic neurons. 

PMID- 24861507
TI  - Changes in muscle coordination and power output during sprint cycling.
AB  - This study investigated the changes in muscle coordination associated to power
      output decrease during a 30-s isokinetic (120rpm) cycling sprint. Modifications
      in EMG amplitude and onset/offset were investigated from eight muscles [gluteus
      maximus (EMGGMAX), vastus lateralis and medialis obliquus (EMGVAS), medial and
      lateral gastrocnemius (EMGGAS), rectus femoris (EMGRF), biceps femoris and
      semitendinosus (EMGHAM)]. Changes in co-activation of four muscle pairs
      (CAIGMAX/GAS, CAIVAS/GAS, CAIVAS/HAM and CAIGMAX/RF) were also calculated.
      Substantial power reduction (60+/-6%) was accompanied by a decrease in EMG
      amplitude for all muscles other than HAM, with the greatest deficit identified
      for EMGRF (31+/-16%) and EMGGAS (20+/-14%). GASonset, HAMonset and GMAXonset
      shifted later in the pedalling cycle and the EMG offsets of all muscles (except
      GASoffset) shifted earlier as the sprint progressed (P<0.05). At the end of the
      sprint, CAIVAS/GAS and CAIGMAX/GAS were reduced by 48+/-10% and 43+/-12%,
      respectively. Our results show that substantial power reduction during fatiguing
      sprint cycling is accompanied by marked reductions in the EMG activity of bi
      articular GAS and RF and co-activation level between GAS and main power producer
      muscles (GMAX and VAS). The observed changes in RF and GAS EMG activity are
      likely to result in a redistribution of the joint powers and alterations in the
      orientation of the pedal forces. 

PMID- 24861508
TI  - Anti-amnesic effect of alkaloid fraction from Lycopodiella cernua (L.) Pic. Serm.
      on scopolamine-induced memory impairment in mice.
AB  - Lycopodiella cernua (L.) Pic. Serm. (Licopodiaceae) has been used in Vietnamese
      folk medicine for treating central nervous system conditions. In this study, the
      alkaloid fraction from the methanol extract of this plant (VLC) was evaluated for
      in vitro acetylcholinesterase (AChE) inhibitory activity in cognition-relevant
      brain areas of mice. In in vivo study, the cognitive-enhancing effect of VLC on
      amnesic mice induced by scopolamine was investigated by assessing a passive
      avoidance and a Morris water maze test. VLC inhibited AChE activity in mouse
      frontal cortex, hippocampus and striatum with IC50 values of 26.7, 32.2 and
      25.7MUg/mL, respectively. Administration of VLC (10, 20, 50 and 100mg/kg, p.o.)
      significantly reversed cognitive impairments in mice by passive avoidance test.
      Treating with VLC (50mg/kg) reduced escape latencies in training trials and
      prolonged swimming times in the target quadrant during the probe trial in the
      water maze task (P<0.05). These results indicated that L. cernua originated from
      Vietnam has anti-cholinesterase activity and might be useful for the treatment of
      cognitive impairment. 

PMID- 24861509
TI  - Association between serum levels of glial cell-line derived neurotrophic factor
      and attention deficits in schizophrenia.
AB  - Several lines of evidence suggest that glial cell-line derived neurotrophic
      factor (GDNF) plays an important role in the pathophysiology of neuropsychiatric
      and neurodegenerative disorders. In this study, we investigated the association
      between GDNF serum levels and the clinical status of medicated patients with
      schizophrenia. Sixty-three medicated patients with schizophrenia and 52 age- and
      sex-matched healthy controls were recruited. Patients were evaluated using the
      brief psychiatry rating scale, the scale for the assessment of negative symptoms
      (SANS) and neuropsychological tests. Serum levels of GDNF were determined using
      an ELISA method. Serum levels of GDNF did not differ between schizophrenia
      patients and controls. Higher GDNF serum levels were associated with better
      performances on the Digit Span in healthy controls but not in schizophrenics. At
      the same time, higher GDNF serum levels were associated with severe attention
      deficits on the SANS subscale, in schizophrenics. Our preliminary study suggests
      that serum levels of GDNF may be an unsuitable biomarker for schizophrenia,
      although it may be associated with working memory in healthy controls and the
      pathophysiology of attention deficits in schizophrenia. 

PMID- 24861511
TI  - Effects of ethanol on sensory stimulus-evoked responses in the cerebellar
      molecular layer in vivo in mice.
AB  - Overdose intake of ethanol can impair cerebellar cortical neurons to integrate
      and transfer external information, resulting in a dysfunction of cerebellar motor
      regulation or cerebellar ataxia. However, the mechanisms underlying ethanol
      impaired transfer of sensory information from cerebellar cortical molecular layer
      neurons remain unclear. In the present study, we investigated the effects of
      ethanol on sensory stimulation-evoked responses in the cerebellar molecular layer
      of urethane-anesthetized mice, by electrophysiological and pharmacological
      methods. Our results demonstrated that air-puff stimulation (30 ms, 50-60 psi) of
      the ipsilateral whisker-pad evoked field potential responses in the molecular
      layer of the cerebellar cortex folium Crus II, which expressed a negative
      component (N1) followed by a gamma-aminobutyric acid receptor A (GABAA)-mediated
      positive component (P1). Cerebellar surface perfusion of ethanol between 2 and
      5mM did not change the latency of the evoked responses and the amplitude of N1,
      but enhanced the amplitude and the area under the curve of P1. Interestingly,
      high concentrations (>20mM) of ethanol induced a significantly decrease in the
      amplitude and area under the curve of P1. Furthermore, high concentration ethanol
      (300 mM) significantly decreased the rise in tau and tau decay value of P1,
      whereas low concentration ethanol (2-5mM) significantly increased these values of
      P1. Inhibition of GABAA receptor activity reversed P1 and also abolished the
      effects of ethanol on sensory stimulation-evoked responses. These results
      indicated that ethanol induced a bidirectional effect on the sensory stimulation
      evoked GABAergic responses in the cerebellar cortical molecular layer, suggesting
      that acute alcohol intake impacted the sensory information processing of
      cerebellar cortex.

PMID- 24861512
TI  - The what-decision in manual action: ERPs for free choice versus specified overt
      goal-related grasping.
AB  - This study explored the neurophysiological mechanisms underlying the what
      decision of planning and execution of an overt goal-related manual action. We
      aimed to differentiate cerebral activity, by means of event-related potentials
      (ERPs), between predominantly self-regulated and instructed actions. In a bar
      transport task, participants were given free or specified choices about the
      initial grip and/or final goal. The ERPs for action execution differed between
      free- and specified-goal conditions, but not between free- and specified-grasp
      conditions. We found differential activity for the goal specification in mid
      frontal, mid-central, and mid-parietal regions from -1100 to -700ms and -500 to
      0ms time-locked to grasping and in anterior right regions from -1900 to -1400ms
      time-locked to movement end. There was no differential activity for grasp
      specifications. These results indicated that neural activity differed between
      free and specified actions, but only for goal conditions, suggesting different
      ways of operation dependent on goal-relatedness. To our knowledge, this was the
      first study to differentiate cerebral activity and its temporal organization
      underlying the what-decision involved in overt goal-related actions. Our results
      support the ideomotor theory by showing that neural processes underlying action
      preparation and execution depend on the anticipated action goal. 

PMID- 24861510
TI  - Molecular and functional identification of a mitochondrial ryanodine receptor in
      neurons.
AB  - Mitochondrial Ca(2+) controls numerous cell functions, such as energy metabolism,
      reactive oxygen species generation, spatiotemporal dynamics of Ca(2+) signaling,
      cell growth and death in various cell types including neurons. Mitochondrial
      Ca(2+) accumulation is mainly mediated by the mitochondrial Ca(2+) uniporter
      (MCU), but recent reports also indicate that mitochondrial Ca(2+)-influx
      mechanisms are regulated not only by MCU, but also by multiple
      channels/transporters. We previously reported that ryanodine receptor (RyR),
      which is a one of the main Ca(2+)-release channels at endoplasmic/sarcoplasmic
      reticulum (SR/ER) in excitable cells, is expressed at the mitochondrial inner
      membrane (IMM) and serves as a part of the Ca(2+) uptake mechanism in
      cardiomyocytes. Although RyR is also expressed in neuronal cells and works as a
      Ca(2+)-release channel at ER, it has not been well investigated whether neuronal
      mitochondria possess RyR and, if so, whether this mitochondrial RyR has
      physiological functions in neuronal cells. Here we show that neuronal
      mitochondria express RyR at IMM and accumulate Ca(2+) through this channel in
      response to cytosolic Ca(2+) elevation, which is similar to what we observed in
      another excitable cell-type, cardiomyocytes. In addition, the RyR blockers
      dantrolene or ryanodine significantly inhibits mitochondrial Ca(2+) uptake in
      permeabilized striatal neurons. Taken together, we identify RyR as an additional
      mitochondrial Ca(2+) uptake mechanism in response to the elevation of [Ca(2+)]c
      in neurons, suggesting that this channel may play a critical role in
      mitochondrial Ca(2+)-mediated functions such as energy metabolism. 

PMID- 24861513
TI  - Co-administration of memantine with epinephrine produces a marked peripheral
      action in intensifying and prolonging analgesia in response to local skin
      pinprick in rats.
AB  - The purpose of this study was to examine the effect of epinephrine as adjuvant
      for memantine or lidocaine as an infiltrative anesthetic. Using a rat model of
      cutaneous trunci muscle reflex (CTMR), we evaluated the effects of adding
      epinephrine to memantine or lidocaine on infiltrative cutaneous analgesia.
      Lidocaine, a known local anesthetic, was used as control. We found that
      epinephrine, memantine, and lidocaine produced a dose-dependent local anesthetic
      effect as infiltrative cutaneous analgesia. On a 50% effective dose (ED50) basis,
      the relative potencies were epinephrine [0.012 (0.006-0.020)MUmol]>memantine
      [4.010 (3.311-4.988)MUmol]>lidocaine [6.177 (5.333-7.218)MUmol] (P<0.05 for each
      comparison). Mixtures of epinephrine (2.7nmol or 13.7nmol) with drugs (memantine
      or lidocaine) at ED50 or ED95, respectively, enhanced the potency and prolonged
      the duration of action on infiltrative cutaneous analgesia. Intraperitoneal
      injection of co-administration of drugs (memantine or lidocaine) at ED95 with
      epinephrine (13.7nmol) produced no cutaneous analgesia (data not shown).
      Epinephrine, memantine, and lidocaine were shown to have local anesthetic effects
      as infiltrative cutaneous analgesia. Epinephrine increased the duration and
      potency of memantine and lidocaine as an infiltrative anesthetic. 

PMID- 24861514
TI  - Acute estrogen surge enhances inflammatory nociception without altering spinal
      Fos expression.
AB  - Chronic pain is a major neurological disorder that can manifest differently
      between genders or sexes. The complex actions of sex hormones may underlie these
      differences; previous studies have suggested that elevated estrogen levels can
      enhance pain perception. The purpose of this study was to investigate the
      hypothesis that acute, activational effects of estradiol (E2) increase persistent
      inflammatory nociception, and anatomically where this modulation occurs. Spinal
      expression of Fos is widely used as a marker of nociceptive activation. This
      study used formalin-evoked nociception in ovariectomized (OVX) adult female rats
      and measured late-phase hindlimb flinching and Fos expression in the spinal cord,
      and their modification by acute estrogen supplementation similar to a proestrus
      surge. Six days after ovariectomy, female rats were injected subcutaneously
      (s.c.) with 10MUg/kg E2 or vehicle. Twenty-four hours later, 50MUL of 1.25% or
      100MUL of 5% formalin was injected into the right hindpaw; hindlimb flinches were
      counted, and spinal cords removed 2h after formalin injection. The numbers of Fos
      expressing neurons in sections of the lumbar spinal cord were analyzed using
      immunohistochemistry. Formalin-induced inflammation produced a dose-dependent
      increase in late-phase hindlimb flinching, and E2 pretreatment increased
      flinching following 5%, but not 1.25% formalin injection. Despite the
      modification of behavior by E2, the number of spinal Fos-positive neurons was not
      altered by E2 pretreatment. These findings demonstrate that an acute proestrus
      like surge in serum estrogen can produce a stimulus-intensity-dependent increase
      in inflammation-evoked nociceptive behavior. However, the lack of effect on
      spinal Fos expression suggests that this enhancement of nociceptive signaling by
      estrogen is independent of changes in peripheral activation of, expression of the
      immediate early gene Fos by, or signal throughput of spinal nociceptive neurons. 

PMID- 24861515
TI  - The selective estrogen receptor modulator, bazedoxifene, reduces ischemic brain
      damage in male rat.
AB  - While the estrogen treatment of stroke is under debate, selective estrogen
      receptor modulators (SERMs) arise as a promising alternative. We hypothesize that
      bazedoxifene (acetate, BZA), a third generation SERM approved for the treatment
      of postmenopausal osteoporosis, reduces ischemic brain damage in a rat model of
      transient focal cerebral ischemia. For comparative purposes, the neuroprotective
      effect of 17beta-estradiol (E2) has also been assessed. Male Wistar rats
      underwent 60min middle cerebral artery occlusion (intraluminal thread technique),
      and grouped according to treatment: vehicle-, E2- and BZA-treated rats. Optimal
      plasma concentrations of E2 (45.6+/-7.8pg/ml) and BZA (20.7+/-2.1ng/ml) were
      achieved 4h after onset of ischemia, and maintained until the end of the
      procedure (24h). Neurofunctional score and volume of the damaged brain regions
      were the main end points. At 24h after ischemia-reperfusion, neurofunctional
      examination of the animals did not show significant differences among the three
      experimental groups. By contrast, both E2- and BZA-treated groups showed
      significantly lower total infarct volumes, BZA acting mainly in the cortical
      region and E2 acting mainly at the subcortical level. Our results demonstrate
      that: (1) E2 at physiological plasma levels in female rats is neuroprotective in
      male rats when given at the acute stage of the ischemic challenge and (2) BZA at
      clinically relevant plasma levels mimics the neuroprotective action of E2 and
      could be, therefore, a candidate in stroke treatment. 

PMID- 24861516
TI  - 6-OHDA induced calcium influx through N-type calcium channel alters membrane
      properties via PKA pathway in substantia nigra pars compacta dopaminergic
      neurons.
AB  - Voltage gated calcium channels (VGCC) are sensitive to oxidative stress, and
      their activation or inactivation can impact cell death. Although these channels
      have been extensively studied in expression systems, their role in the brain,
      particularly in the substantia nigra pars compacta (SNc), remain controversial.
      In this study, we assessed 6-hydroxydopamine (6-OHDA) induced transformation of
      firing pattern and functional changes of calcium channels in SNc dopaminergic
      neurons. Application of 6-OHDA (0.5-2mM) evoked a dose-dependent, desensitizing
      inward current and intracellular free calcium concentration ([Ca(2+)]i) rise. In
      voltage clamp, omega-conotoxin-sensitive Ca(2+) current modulation mediated by 6
      OHDA reflected an altered sensitivity. Furthermore, we found that 6-OHDA
      modulated Ca(2+) currents through PKA pathway. These results provided evidence
      for the potential role of VGCCs and PKA involved in oxidative stress in
      degeneration of SNc neurons in Parkinson's disease (PD). 

PMID- 24861517
TI  - Effects of REM sleep deprivation on sensorimotor gating and startle habituation
      in rats: role of social isolation in early development.
AB  - The present study examined the role of rapid eye movement (REM) sleep on
      sensorimotor gating function in a developmentally rodent model of schizophrenic
      spectrum disorders. Startle magnitude, prepulse inhibition (PPI) and startle
      habituation in an acoustic startle test were measured after 72-h of REM sleep
      deprivation (REMSD) in 14-week-old rats that were reared in one of the following
      conditions: control social interaction, 2-week isolation, and continuous
      isolation, since weaning. The results showed that REMSD significantly inhibited
      rats' PPI in socially controlled rats, and rats in two isolation groups appeared
      less sensitive to REMSD. After REMSD, startle habituation was significantly
      reduced in continuous-isolated rats but not in 2-week-isolated rats. These data
      indicate that REM sleep is essential for PPI; REMSD inhibits startle habituation
      in rats with continuous social isolation. In addition, social interaction, in
      early life or for the whole life, functions differently to the sensorimotor
      gating. 

PMID- 24861518
TI  - Haloperidol treatment downregulates DCC expression in the ventral tegmental area.
AB  - A core feature in the pathophysiology of schizophrenia is abnormal development
      and function of mesocorticolimbic dopamine (DA) circuitry. We have previously
      shown that variations in the function of the netrin-1 receptor, deleted in
      colorectal cancer (DCC), result in changes to the development, organization and
      ongoing plasticity of DA circuitry. In rodents, repeated exposure to the indirect
      DA-agonist, amphetamine upregulates DCC expression in the ventral tegmental area
      (VTA), but not in DA terminal regions. This elevation in DCC expression is
      associated with increased vulnerability to developing and maintaining sensitized
      mesolimbic DA function. Antipsychotic medications remain the best treatment
      option for managing the symptoms in schizophrenia. The peak effects of these
      medications are gradual, suggesting that a therapeutic component of antipsychotic
      treatment involves structural reorganization. Here we assessed whether repeated
      exposure to typical and atypical antipsychotics could also regulate DCC. Adult
      mice were orally administered haloperidol, clozapine, or risperidone via their
      drinking water for 4 weeks. Levels of DCC were measured by Western blot analysis
      of tissue punches of the VTA, medial prefrontal cortex, nucleus accumbens, and
      dorsal striatum. Haloperidol decreased DCC levels by approximately 50% in the
      VTA, but not in DA targets. Furthermore, haloperidol did not alter UNC-5
      homologue levels, another family of netrin-1 receptors, confirming that its
      effects target DCC-mediated netrin-1 signaling specifically. The atypical
      antipsychotics did not alter DCC expression. These results suggest that typical
      antipsychotics induce selective functional reorganization in the VTA via DCC
      mediated netrin-1 signaling. 

PMID- 24861519
TI  - Mitogen-activated protein kinase (MAPK) phosphatase-3 (MKP-3) displays a p-JNK
      MAPK substrate preference in astrocytes in vitro.
AB  - Mitogen-activated protein kinases (MAPKs) play critical roles in the central
      nervous system immune responses through glial function, which are regulated with
      relative selectivity (or preference) by MAPK phosphatases (MKP). Phosphorylated
      extracellular signal-regulated protein kinase (p-ERK) is preferentially
      dephosphorylated by MKP-3, which display little activity over p-p38 and p-c-Jun
      NH2-terminal kinases (p-JNK). It has been proposed that these substrate
      preferences may vary depending on tissue or functional cellular processes. Since
      astrocytes display a prominent activity of JNK>ERK under stressed or reactive
      phenotype, we hypothesize that MKP-3 possess a similar or differential substrate
      preference in astrocytes for JNK and ERK (ERK=JNK or JNK>ERK). We generated
      transient expression of MKP-3 by transfecting a specific cDNA in primary rat
      neonatal brain cortex astrocytes. Cells were stimulated with lipopolysaccharide
      (LPS), and MAPKs and downstream pro-inflammatory products were measured by
      Western blot and ELISA analyses. MKP-3 expression in primary astrocytes reduced
      LPS-induced p-ERK and p-p38 by ~50%, and p-JNK by ~75%, and moderately reduced
      nitrite oxide (NO), while completely blocked Interleukin (IL)-6 and tumor
      necrosis factor alpha (TNFalpha). We confirmed MKP-3 specific activity by
      developing a BV-2 microglia cell line stably overexpressing MKP-3 and using a
      specific siRNA against MKP-3. Our data demonstrate MKP-3 has differential
      substrate preference in astrocytes compared to other cells types, since it
      preferentially dephosphorylated p-JNK over p-ERK. Our results indicate also that
      astrocytic immune functions can be modulated by MKP-3 induction, a strategy that
      could be beneficial in neurological conditions in which astrocytes play a
      pathophysiological role, i.e. persistent pain. 

PMID- 24861520
TI  - Cu2+ ion responsive solvent-free quantum dots.
AB  - Three quantum dots (QDs) nanofluids modified with different lengths of PEG
      chainsare synthesized, and the property-structure relationship of QDs nanofluids
      is established, to achieve QDs nanofluids with tunable fluidic or optical
      performance. Notably, the proposed QDs nanofluids demonstrate a selective
      response towards Cu(2+)-based on both fluorescence and contact angle.

PMID- 24861521
TI  - Multidrug-resistant bacteria in solid organ transplant recipients.
AB  - Bacteria are the leading cause of infections after solid organ transplantation.
      In recent years, a progressive growth in the incidence of multidrug-resistant
      (MDR) and extensively-drug-reistant (XDR) strains has been observed. While
      methicillin-resistant Staphylococcus aureus (MRSA) infection is declining in non
      transplant and SOT patients worldwide, vancomycin-resistant enterococci, MDR/XDR
      Enterobacteriaceae and MDR/XDR non-fermenters are progressively growing as a
      cause of infection in solid organ transplant (SOT) patients and represent a
      global threat. Some SOT patients develop recurrent infections, related to
      anatomical defects in many cases, which are difficult to treat and predispose
      patients to the acquisition of MDR pathogens. As the antibiotics active against
      MDR bacteria have several limitations for their use, which include less clinical
      experience, higher incidence of adverse effects and less knowledge of the
      pharmacokinetics of the drug, and, in most cases, are only available for
      parenteral administration, it is mandatory to know the main characteristics of
      these drugs to safely treat SOT patients with MDR bacterial infections.
      Nonetheless, preventive measures are the cornerstone of controlling the spread of
      these pathogens. Thus, applying the Center for Disease Control and Prevention's
      and the European Society of Clinical Microbiology and Infectious Diseases's
      recommended antibiotic policies and strategies to control the transmission of MDR
      strains in the hospital setting is essential for the management of SOT patients. 

PMID- 24861523
TI  - The ideal timing of ureteric stent removal in transplantation patients.

PMID- 24861522
TI  - Etravirine plasma exposure is associated with virological efficacy in treatment
      experienced HIV-positive patients.
AB  - Etravirine is a non-nucleoside reverse transcriptase inhibitor used in
      combination with other antiretrovirals for the treatment of HIV infection. Given
      previous conflicting results aim of this study was to investigate whether
      etravirine plasma exposure was associated with virological outcome. Adult HIV
      positive patients starting etravirine with detectable HIV viral loads were
      included if highly adherent (<90% of the doses) and if steady-state plasma
      concentrations were available (measured through a validated HPLC-PDA method).
      Virological success was defined as reaching and maintaining viral suppression
      (HIV RNA <50copies/mL) during follow up. Fifty-nine (84.7% male) patients were
      included: baseline CD4+ T-lymphocyte and HIV RNA were 276cells/MUL (101-419) and
      3.99Log10copies/mL (3.11-4.91), respectively. Darunavir/ritonavir (n=21, 35.6%)
      and raltegravir plus maraviroc (n=33, 55.9%) were the most common associated
      antiretrovirals. 240 trough samples were available (3-7 per patient); etravirine
      trough concentrations (Ctrough) and weighted genotypic inhibitory quotients
      (wgIQ) were 426ng/mL (266-763) and 408ng/mL/mutation (227-663), respectively.
      Virological success was observed in 49 patients (83.1%). Genotypic sensitivity of
      associated drugs (GSS) ?2 (p=0.03), etravirine Ctrough >300ng/mL (p=0.02) and
      etravirine wgIQ >276ng/mL/mutation (p=0.02) were associated with virological
      success; at multivariate Cox proportional analysis etravirine wgIQ
      <276ng/mL/mutation (p=0.012) and baseline CD4 <200cell/MUL (p=0.043) were
      independently associated with virological failure. In a cohort of experienced
      patients etravirine exposure as well as immune status were associated with
      virological success; two cut off values (300ng/mL and 276ng/mL) were proposed for
      etravirine Ctrough and wgIQ and need to be confirmed in prospective studies. 

PMID- 24861524
TI  - Locking plate and screw fixation after tibial plateau leveling osteotomy reduces
      postoperative infection rate in dogs over 50 kg.
AB  - OBJECTIVE: To assess the influence of locking plate and screw implants on
      postoperative infection rate in dogs >50 kg undergoing tibial plateau leveling
      osteotomy (TPLO). STUDY DESIGN: Retrospective case series. ANIMALS: Dogs >50 kg
      (n = 208) that had TPLO. METHODS: Medical records (January 2003-September 2011)
      were reviewed for dogs that had TPLO. Type of implant used (locking plate and
      screw fixation [LP] and dynamic compression plate and screw fixation [NLP]), use
      of postoperative antibiotics and presence of postoperative infection were
      recorded. Multivariate analysis was performed. RESULTS: Forty dogs (21.3%) had
      clinical signs compatible with postoperative infection. A positive microbiology
      swab was available in 16/40 cases (40%). Administration of postoperative
      antibiotics was associated with a lower incidence of infection (P = .006) and the
      use of NLP was associated with a higher incidence of infection (P = .01).
      CONCLUSIONS: Use of LP construct and postoperative antibiotic therapy
      significantly decreased infection rate in dogs >50 kg that have TPLO.

PMID- 24861525
TI  - Genetic analysis in APC, KRAS, and TP53 in patients with stomach and colon
      cancer.
AB  - BACKGROUND: Stomach cancer (SC) and colorectal cancer (CRC) present with high
      rates of incidence and mortality in the worldwide population. These 2 tumors are
      characterized by great genetic heterogeneity. Up to now, there have been no
      molecular studies that analyze the mutations in the APC, KRAS, and TP53 genes in
      the Colombian/Latin American population. OBJECTIVES: To analyze mutations in the
      APC, KRAS, and TP53 genes through direct sequencing in 59 patients with SC and
      CRC. PATIENTS AND METHODS: Twenty-nine patients with SC and 30 with CRC were
      studied. An analysis of the mutations of the 3 genes was carried out using
      polymerase chain reaction and direct sequencing techniques. RESULTS: A 30.5%
      total mutation frequency was found. The most frequently mutated gene was APC
      (15.3%), followed by KRAS (10.1%) and TP53 (5.1%). The CRC samples had a mutation
      frequency of 46.7% and it was 13.3% in the SC samples (P=.006). No mutations
      occurred simultaneously in the 3 genes. Mutations in 2 genes were found in only 6
      tumor samples (10%). There was also a high frequency of polymorphisms in both
      types of cancer, the most common of which was the rs41115 polymorphism, located
      on the APC gene. CONCLUSION: The APC, KRAS, and TP53 gene mutations were more
      common in CRC than in SC. Our results suggest the existence of different genetic
      pathways in the carcinogenesis of SC and CRC and they also reveal a particular
      mutation frequency in the Colombian patients studied; this could be influenced by
      factors related to the environment, ethnicity, and lifestyle of this population.

PMID- 24861526
TI  - The role of oxidative stress in the development of alcoholic liver disease.
AB  - BACKGROUND: Alcohol is the most accepted addictive substance worldwide and its
      consumption is related to multiple health, economic, and social problems. The
      liver is the organ in charge of ethanol metabolism and it is susceptible to
      alcohol's toxic effects. OBJETIVOS: To provide a detailed review of the role of
      oxidative stress in alcoholic liver disease and the mechanisms of damage
      involved, along with current information on the hepatoprotective effectiveness of
      the molecules that have been studied. MATERIALS AND METHODS: A search of the
      PubMed database was conducted using the following keywords oxidative stress,
      alcoholic liver damage, alcoholic cirrhosis, and antioxidants. There was no time
      limit for gathering all available information on the subject at hand. RESULTS:
      According to the literature reviewed, oxidative stress plays an important role in
      the pathogenesis of alcoholic liver damage. Molecules such as reactive oxygen
      species (ROS) and reactive nitrogen species (RNS), formed during ethanol
      metabolism, structurally and functionally modify organic molecules. Consequently,
      biologic processes are altered and hepatocytes are sensitized to the action of
      cytokines like tumor necrosis factor-alpha, as well as to the action of
      endotoxins, activating signaling pathways such as those controlled by nuclear
      factor kappa B, extracellular signal regulated kinases, and mitogen activated
      protein kinase. CONCLUSIONS: Oxidative stress plays an important role in the
      development of liver damage resulting from alcohol consumption. The molecules
      that have currently displayed a hepatoprotective effect in preclinical and
      clinical trials must be studied further so that their effectiveness can be
      confirmed and they can possibly be used as adjuvant treatments for this disease.

PMID- 24861527
TI  - [Perforated gastric volvulus due to incarcerated paraesophageal hernia].

PMID- 24861528
TI  - An infrequent cause of iron-deficiency anemia: blue rubber bleb nevus syndrome.

PMID- 24861529
TI  - Reprint of: keratin intermediate filaments: differences in the sequences of the
      Type I and Type II chains explain the origin of the stability of an enzyme
      resistant four-chain fragment.
AB  - Previous studies have shown that a strong interaction exists between oppositely
      directed 1B molecular segments in the intermediate filaments of trichocyte
      keratins. A similar interaction has been identified as having a significant role
      in the formation of unit-length filaments, a precursor to intermediate filament
      formation. The present study is concerned with the spatial relationship of these
      interacting segments and its dependence on differences in the amino acid
      sequences of the two-chain regions that constitute the 1B molecular segment. It
      is shown that along a particular line of contact both chain segments possess an
      elevated concentration of residues with a high propensity for dimer formation.
      The transition from the reduced to the oxidized state involves a simple axial
      displacement of one molecular segment relative to the other, with no attendant
      rotation of either segment. This changes the inter-relationship of the two 1B
      molecular segments from a loosely packed form to a more compact one. After the
      slippage eight of the cysteine residues in the dimer are precisely aligned to
      link up and form the disulfide linkages as observed. The two remaining cysteine
      residues are located on the outside of the dimer and are presumably involved in
      inter-dimer bonding. The existence of a unique line of contact requires that two
      chains in the molecule have different amino acid compositions with the clustering
      of dimer-favoring residues phased by half the pitch length of the coiled coil. 

PMID- 24861530
TI  - Heterogeneous arsenic enrichment in meta-sedimentary rocks in central Maine,
      United States.
AB  - Arsenic is enriched up to 28 times the average crustal abundance of 4.8 mg kg(-1)
      for meta-sedimentary rocks of two adjacent formations in central Maine, USA where
      groundwater in the bedrock aquifer frequently contains elevated As levels. The
      Waterville Formation contains higher arsenic concentrations (mean As 32.9 mg kg(
      1), median 12.1 mg kg(-1), n=38) than the neighboring Vassalboro Group (mean As
      19.1 mg kg(-1), median 6.0 mg kg(-1), n=38). The Waterville Formation is a
      pelitic meta-sedimentary unit with abundant pyrite either visible or observed by
      scanning electron microprobe. Concentrations of As and S are strongly correlated
      (r=0.88, p<0.05) in the low grade phyllite rocks, and arsenic is detected up to
      1944 mg kg(-1) in pyrite measured by electron microprobe. In contrast,
      statistically significant (p<0.05) correlations between concentrations of As and
      S are absent in the calcareous meta-sediments of the Vassalboro Group, consistent
      with the absence of arsenic-rich pyrite in the protolith. Metamorphism converts
      the arsenic-rich pyrite to arsenic-poor pyrrhotite (mean As 1 mg kg(-1), n=15)
      during de-sulfidation reactions: the resulting metamorphic rocks contain arsenic
      but little or no sulfur indicating that the arsenic is now in new mineral hosts.
      Secondary weathering products such as iron oxides may host As, yet the
      geochemical methods employed (oxidative and reductive leaching) do not
      conclusively indicate that arsenic is associated only with these. Instead,
      silicate minerals such as biotite and garnet are present in metamorphic zones
      where arsenic is enriched (up to 130.8 mg kg(-1) As) where S is 0%.
      Redistribution of already variable As in the protolith during metamorphism and
      contemporary water-rock interaction in the aquifers, all combine to contribute to
      a spatially heterogeneous groundwater arsenic distribution in bedrock aquifers.

PMID- 24861531
TI  - Mercury in the Canadian Arctic terrestrial environment: an update.
AB  - Contaminants in the Canadian Arctic have been studied over the last twenty years
      under the guidance of the Northern Contaminants Program. This paper provides the
      current state of knowledge on mercury (Hg) in the Canadian Arctic terrestrial
      environment. Snow, ice, and soils on land are key reservoirs for atmospheric
      deposition and can become sources of Hg through the melting of terrestrial ice
      and snow and via soil erosion. In the Canadian Arctic, new data have been
      collected for snow and ice that provide more information on the net accumulation
      and storage of Hg in the cryosphere. Concentrations of total Hg (THg) in
      terrestrial snow are highly variable but on average, relatively low (<5 ng L(
      1)), and methylmercury (MeHg) levels in terrestrial snow are also generally low
      (<0.1 ng L(-1)). On average, THg concentrations in snow on Canadian Arctic
      glaciers are much lower than those reported on terrestrial lowlands or sea ice.
      Hg in snow may be affected by photochemical exchanges with the atmosphere
      mediated by marine aerosols and halogens, and by post-depositional redistribution
      within the snow pack. Regional accumulation rates of THg in Canadian Arctic
      glaciers varied little during the past century but show evidence of an increasing
      north-to-south gradient. Temporal trends of THg in glacier cores indicate an
      abrupt increase in the early 1990 s, possibly due to volcanic emissions, followed
      by more stable, but relatively elevated levels. Little information is available
      on Hg concentrations and processes in Arctic soils. Terrestrial Arctic wildlife
      typically have low levels of THg (<5 MUg g(-1) dry weight) in their tissues,
      although caribou (Rangifer tarandus) can have higher Hg because they consume
      large amounts of lichen. THg concentrations in the Yukon's Porcupine caribou herd
      vary among years but there has been no significant increase or decrease over the
      last two decades.

PMID- 24861532
TI  - A computational method of predicting regulatory interactions in Arabidopsis based
      on gene expression data and sequence information.
AB  - Inferring transcriptional regulatory interactions between transcription factors
      (TFs) and their targets has utmost importance for understanding the complex
      regulatory mechanisms in cellular system. In this paper, we introduced a
      computational method to predict regulatory interactions in Arabidopsis based on
      gene expression data and sequence information. Support vector machine (SVM) and
      Jackknife cross-validation test were employed to perform our method on a
      collected dataset including 178 positive samples and 1068 negative samples.
      Results showed that our method achieved an overall accuracy of 98.39% with the
      sensitivity of 94.88%, and the specificity of 93.82%, which suggested that our
      method can serve as a potential and cost-effective tool for predicting regulatory
      interactions in Arabidopsis. 

PMID- 24861533
TI  - Changes in preterm breast milk nutrient content in the first month.
AB  - BACKGROUND: The primary aim of the study was to investigate the changes in
      composition of breast milk from mothers with preterm infants (gestation age < 35
      weeks) during the first 4-6 weeks of lactation. METHODS: Breast milk from 17
      mothers who had delivered preterm infants was collected longitudinally for 4-6
      weeks. Breast milk from 15 mothers of full-term infants was also collected at the
      1(st) week and 4(th) week. Fat, protein, lactose, energy, minerals (calcium and
      phosphate), and immune components [secretory immunoglobulin A (IgA), leptin,
      lysozyme, and lactoferrin] content were measured weekly in each participant. A
      mid-infrared human milk analyzer was used to measure the protein, fat, and
      lactose contents. Calcium and phosphate components were checked via
      spectrophotometry. The concentrations of major immune components (secretory IgA,
      lactoferrin, lysozyme, and leptin) were quantified using enzyme-linked
      immunosorbent assay kits. RESULTS: Eighty samples from 17 preterm mothers were
      collected. The mean gestational age was 29.88 +/- 2.39 weeks. There were
      significant changes in nutrient components during these periods, with increases
      in lactose (p < 0.001), lipid (p = 0.001), calorie (p = 0.012), and phosphate (p
      = 0.022) concentration and decreases in protein (p < 0.001) and secretory IgA (p
      < 0.001) concentration. There were no differences in calcium (p = 0.919),
      lactoferrin (p = 0.841), leptin (p = 0.092), and lysozyme (p = 0.561) levels.
      Furthermore, there were no significant differences in most components of breast
      milk between full-term and preterm mothers. CONCLUSION: The longitudinal study
      revealed significant changes in macronutrient contents and secretory IgA
      concentration in preterm milk over the 4-6 week period, which is compatible with
      the results of previous studies. The quantification of phosphate in preterm
      breast milk was lower than the normal range, suggesting that close monitoring of
      body bone mass may be indicated. More studies are warranted to evaluate the
      clinical significance of alterations of major milk components during the
      postnatal stage.

PMID- 24861534
TI  - Therapy for neonatal hyperoxia-induced lung injury.

PMID- 24861535
TI  - Renal excretion of water-soluble contrast media after enema in neonates and small
      infants.

PMID- 24861536
TI  - Severe Hemolytic Jaundice in a Neonate with a Novel COL4A1 Mutation.
AB  - We report our experience with a preterm infant with severe hemolytic jaundice who
      required exchange transfusion just after birth. The patient was negative for
      alloimmune hemolysis as a result of maternal-fetal blood type incompatibility,
      and tests for inherited defects in erythrocyte metabolism, membrane function, and
      hemoglobin synthesis were normal. We also performed a bone marrow examination,
      but could not identify the cause of hemolysis. The patient had several other
      complications, including porencephaly, epilepsy, elevated serum levels of
      creatine kinase, and persistent microscopic hematuria. Later, we detected a
      genetic mutation in COL4A1, which was recently found to be associated with
      hemolytic anemia. We therefore believe that all of the patient's clinical
      features, including hemolytic anemia, were due to the mutation in COL4A1. Genetic
      testing for COL4A1 mutations is recommended in neonates who exhibit hemolytic
      disease of unknown etiology, especially when other complications compatible with
      COL4A1-related disorders are present.

PMID- 24861537
TI  - Socioeconomic and geographic differences in immediate reconstruction after
      mastectomy in the United States.
AB  - Disparities are evident in breast cancer diagnosis, treatment, and outcomes. This
      study examines multiple socioeconomic and geographic regions across the US to
      determine if disparities exist in the type of reconstruction obtained after
      mastectomy. This is a retrospective study evaluating socioeconomic and geographic
      variables of 14,764 women who underwent mastectomy in 2008 using the Nationwide
      Inpatient Sample (NIS). Statistical analysis was performed on three groups of
      women: patients without reconstruction (NR), patients who underwent breast
      implant/tissue expander reconstruction (TE), and patients with autologous
      reconstruction such as free or pedicled flaps (FLAP). The majority of patients
      (63.9%) had NR, while 23.9% had TE and 12.2% underwent FLAP. Compared to patients
      with NR, women with TE or FLAP were younger (64.9 years versus 51.3 and 51.1
      years, p < 0.001), had fewer chronic conditions (2.60 and 2.54 chronic conditions
      for TE and FLAP respectively versus 3.85 for NR, p < 0.001) and higher mean
      hospital charges ($42,850 TE and $48,680 FLAP versus $22,300 NR, p < 0.001). Both
      Medicare and Medicaid insurance carriers had a higher proportion of women that
      did not get reconstructed compared to other insurance types (p < 0.001). Compared
      to NR, reconstructed women more often lived in urban areas and zip codes with
      higher average incomes (p < 0.001). This is the first national study analyzing
      insurance type and geographic variations to show statistically significant
      disparities in rate and type of immediate reconstruction after mastectomy. These
      inequalities need to be addressed to extend immediate reconstruction options to
      all women undergoing mastectomy.

PMID- 24861538
TI  - A survey conducted immediately after the 2011 Great East Japan Earthquake:
      evaluation of infectious risks associated with sanitary conditions in evacuation
      centers.
AB  - In cooperation with the Miyagi prefectural government, we conducted a survey of
      the management of sanitation at evacuation centers and the health of the evacuees
      by visiting 324 evacuation centers at two weeks after the 2011 Great East Japan
      Earthquake. The facilities often used as evacuation centers were community
      centers (36%), schools (32.7%) and Nursing homes (10.2%). It was more difficult
      to maintain a distance of at least 1 m between evacuees at the evacuation centers
      with a larger number of residents. At evacuation centers where the water supply
      was not restored, hygienic handling of food and the hand hygiene of the cooks
      were less than adequate. Among evacuation centers with <=50 evacuees, there was a
      significant difference in the prevalence rate of digestive symptoms between the
      centers with and without persons in charge of health matters (0.3% vs. 2.1%,
      respectively, p < 0.001). The following three factors had an important influence
      on the level of sanitation at evacuation centers and the health of evacuees: 1)
      the size of the evacuation center, 2) the status of the water supply, and 3) the
      allocation of persons in charge of health matters. Given that adjusting the
      number of evacuees to fit the size of the evacuation center and prompt
      restoration of the water supply are difficult to achieve immediately after an
      earthquake, promptly placing persons in charge of health matters at evacuation
      centers is a practicable and effective measure, and allocation of at least one
      such person per 50 evacuees is desirable.

PMID- 24861539
TI  - 'To move or not to move': a national survey among professionals on beliefs and
      considerations about the place of end-of-life care for people with intellectual
      disabilities.
AB  - BACKGROUND: The aim of this article was to investigate the beliefs and
      considerations of professionals concerning an appropriate environment for end-of
      life care for people with intellectual disabilities (ID). METHOD: A survey
      questionnaire was composed based on a scan of relevant literature and the results
      of group interviews with professionals, family members and people with ID. The
      questionnaire focused on the respondents' general beliefs about an appropriate
      environment for end-of-life care and their specific considerations regarding the
      place of care of the last client for whom the respondent provided end-of-life
      care. The questionnaire was sent to 294 care staff members recruited from a
      nationally representative panel of nurses and social workers, 273 ID physicians
      recruited from the members list of the Dutch professional association of ID
      physicians, and 1000 general practitioners (GPs) recruited from a nationally
      representative sample from a national registration of GPs. RESULTS: The overall
      response was 46%. Professionals predominantly believe that all efforts should be
      made to ensure that a person with ID receives end-of-life care in their own home
      environment, and that 24/7 care is available. Respondents indicated that most of
      the clients (79%) who had last received end-of-life care from an ID care service
      were able to stay in their own home environment. Decisions to keep the client in
      their own home environment were primarily based on the familiarity of the
      environment and the expertise of the team in end-of-life care. Insufficient
      expertise and a lack of adequate equipment were the main considerations in
      decisions to move a client. Despite the belief of care staff in particular that
      the wishes of the person with ID should always be leading when deciding on the
      place of end-of-life care, only 8% of the care staff and ID physicians explicitly
      mentioned that the client's wishes were taken into account in actual decision
      making. CONCLUSIONS: Professionals agree that end-of-life care for people with ID
      should preferably take place in the client's home environment, even when nursing
      expertise, experience and adequate equipment are not (yet) in place. Nonetheless,
      a lack of expertise in end-of-life care is the foremost consideration in
      decisions to move a client. If ID care services want to promote end-of-life care
      in the client's own home, we recommend formulating a policy on how to realise end
      of-life care in the client's own home environment and provide sufficient training
      and support for staff. To involve people with ID as much as possible, we
      recommend that professionals integrate more collaborative principles in decision
      making about the place of end-of-life care.

PMID- 24861541
TI  - Acute toxicity test of CuO nanoparticles using human mesenchymal stem cells.
AB  - Despite the growing interest in nanoparticles (NPs), standardized procedures for
      the evaluation of their toxicity have not been defined. The risk of human
      exposure is rapidly increasing and reliable toxicity test systems are urgently
      needed. In vitro methods are ideal in toxicology research because they can
      rapidly provide reproducible results while preventing the use of animals.
      Recently, a new test for acute toxicity based on the use of human bone marrow
      mesenchymal stem cells (hBMMSCs) has been developed and successfully tested in
      our laboratory following the Interagency Coordinating Committee on the Validation
      of Alternative Methods guidelines. Along these lines, the aim of this study is to
      evaluate the acute cytotoxicity of copper oxide (CuO) NPs using the new toxicity
      test based on hBMMSCs. Our results show that CuO NPs are much more toxic compared
      to micrometer ones. Specifically, CuO NP exposure exhibits a significant
      cytotoxicity at all the concentrations used, with an IC50 value of 2.5 +/- 0.53
      ug/ml. On the other hand, CuO microsized particle exposure exhibits a very low
      cytotoxicity at the same concentrations, with an IC50 value of 72.13 +/- 16.2
      ug/ml.

PMID- 24861540
TI  - Verbal strategies and nonverbal cues in school-age children with and without
      specific language impairment (SLI).
AB  - BACKGROUND: Considerable evidence suggests that performance across a variety of
      cognitive tasks is effectively supported by the use of verbal and nonverbal
      strategies. Studies exploring the usefulness of such strategies in children with
      specific language impairment (SLI) are scarce and report inconsistent findings.
      AIMS: To examine the effects of induced labelling and auditory cues on the
      performance of children with and without SLI during a categorization task.
      METHODS & PROCEDURES: Sixty-six school-age children (22 with SLI, 22 age-matched
      controls, 22 language-matched controls) completed three versions of a computer
      based categorization task: one baseline, one requiring overt labelling and one
      with auditory cues (tones) on randomized trial blocks. OUTCOMES & RESULTS:
      Labelling had no effect on performance for typically developing children but
      resulted in lower accuracy and longer reaction time in children with SLI. The
      presence of tones had no effect on accuracy but resulted in faster reaction time
      and post-error slowing across groups. CONCLUSIONS & IMPLICATIONS: Verbal strategy
      use was ineffective for typically developing children and negatively affected
      children with SLI. All children showed faster performance and increased
      performance monitoring as a result of tones. Overall, effects of strategy use in
      children appear to vary based on task demands, strategy domain, age and language
      ability. Results suggest that children with SLI may benefit from auditory cues in
      their clinical intervention but that further research is needed to determine when
      and how verbal strategies might similarly support performance in this population.

PMID- 24861542
TI  - Polarization fatigue of organic ferroelectric capacitors.
AB  - The polarization of the ferroelectric polymer P(VDF-TrFE) decreases upon
      prolonged cycling. Understanding of this fatigue behavior is of great
      technological importance for the implementation of P(VDF-TrFE) in random-access
      memories. However, the origin of fatigue is still ambiguous. Here we investigate
      fatigue in thin-film capacitors by systematically varying the frequency and
      amplitude of the driving waveform. We show that the fatigue is due to
      delamination of the top electrode. The origin is accumulation of gases, expelled
      from the capacitor, under the impermeable top electrode. The gases are formed by
      electron-induced phase decomposition of P(VDF-TrFE), similar as reported for
      inorganic ferroelectric materials. When the gas barrier is removed and the
      waveform is adapted, a fatigue-free ferroelectric capacitor based on P(VDF-TrFE)
      is realized. The capacitor can be cycled for more than 10(8) times, approaching
      the programming cycle endurance of its inorganic ferroelectric counterparts. 

PMID- 24861543
TI  - USSTRIDE program is associated with competitive Black and Latino student
      applicants to medical school.
AB  - PURPOSE: We compared MCAT scores, grade point averages (GPAs), and medical school
      acceptance rates of Black and Latino students in an outreach program called
      Undergraduate Science Students Together Reaching Instructional Diversity and
      Excellence (USSTRIDE) to non-USSTRIDE students. We hypothesized that Black and
      Latino participants in USSTRIDE had higher acceptance rates to medical school,
      higher MCAT scores, and college GPAs when compared to other Black and Latino
      medical school applicants from our institution. METHODS: The academic performance
      (GPAs and MCAT scores) and acceptance and matriculation rate data on all Black
      and Latino Florida State University applicants to any medical school from 2008 to
      2012 were collected from the AIS/AMCAS database and separated into two comparison
      groups (USSTRIDE vs. Non-USSTRIDE). Independent sample T-tests and chi-square
      analysis, Cohen's D test, and odds ratios were determined. RESULTS: Average
      science GPA was 3.47 for USSTRIDE students (n=55) and 3.45 for non-USSTRIDE
      students (n=137, p=0.68, d=0.0652). Average cumulative GPA was 3.57 for USSTRIDE
      students and 3.54 for non-USSTRIDE students (p=0.45, d=0.121). Average MCAT score
      was 23 for USSTRIDE students and 25 for non-USSTRIDE students (p=0.02, d=0.378).
      Twenty-three percent of accepted USSTRIDE students and 29% of accepted non
      USSTRIDE students had multiple acceptances (p=0.483, OR 1.38, 95% CI 0.52-3.88).
      Forty-nine percent of non-USSTRIDE students and 75% of USSTRIDE students
      matriculated in medical school (p=0.001, OR 3.13 95% CI 1.51-6.74). About 78.6%
      of USSTRIDE students matriculated at FSU's medical school compared to 36.2% of
      non-USSTRIDE students (p<0.01). CONCLUSIONS: USSTRIDE and non-USSTRIDE students
      had similar science and cumulative GPAs. USSTRIDE students' MCAT scores were
      lower but acceptance rates to medical school were higher. Participation in
      USSTRIDE is associated with increased acceptance rates for Black and Latino
      students to our medical school. This finding is true for other medical schools as
      USSTRIDE students are as likely as non-USSTRIDE students to have multiple
      acceptances.

PMID- 24861544
TI  - Laparoscopic ultrasonography versus intra-operative cholangiogram for the
      detection of common bile duct stones during laparoscopic cholecystectomy: a meta
      analysis of diagnostic accuracy.
AB  - BACKGROUND: Routine intra-operative cholangiography (IOC) during laparoscopic
      cholecystectomy is often not performed because of increased operative time,
      radiation, and failure rate. Laparoscopic ultrasound (LUS) is a less invasive
      alternative but studies comparing it to IOC have been of small sample size. This
      study aims to assess the diagnostic accuracy of LUS in detecting common bile duct
      (CBD) stones compared to IOC. METHODS: This meta-analysis was executed and
      reported in accordance with the Preferred Reporting Items for Systematic Reviews
      and Meta- Analyses (PRISMA) statement. 11 comparative studies (1994-2013)
      reporting on 12 patient groups were included. A bivariate model for diagnostic
      meta-analysis was used to attain overall pooled sensitivity and specificity for
      IOC and LUS, and their relationship assessed using a hierarchical summary
      receiver operating characteristic model with meta-regression. RESULTS: IOC had a
      pooled sensitivity of 0.87 (95% CI 0.77-0.93) and a pooled specificity of 0.99
      (95% CI 0.98-0.99) with no significant heterogeneity. The diagnostic Odds Ratio
      (OR) was 442 (95% CI 196-997) and pooled weighted Area Under the Curve (AUC) was
      0.99 (95% CI: 0.98-1.0). LUS had a pooled sensitivity of 0.87 (95% CI 0.80-0.92)
      and a specificity of 1.00 (95% CI 0.99-1.00). Heterogeneity was significant for
      specificity results. The diagnostic Odds Ratio (OR) was 1171 (95% CI 372-3689)
      and the pooled, weighted AUC was 1 (95% CI: 0.99-1). Meta-regression did not
      identify factors that significantly predict diagnostic accuracy. CONCLUSIONS: LUS
      is a potentially useful imaging modality to confirm the absence of CBD stones
      without needing to cannulate the biliary system.

PMID- 24861545
TI  - A decade of bariatric surgery. What have we learned? Outcome in 520 patients from
      a single institution.
AB  - BACKGROUND: Today a variety of bariatric surgical procedures is available and,
      currently, it is difficult to identify the most effective option based on patient
      characteristics and comorbidities. Aim of this retrospective study is to evaluate
      the efficacy of four different techniques; Intragastric Balloon (IB),
      Laparoscopic Adjustable Gastric Banding (LAGB), Laparoscopic Sleeve Gastrectomy
      (LSG) and Laparoscopic Mini Gastric Bypass (LMGB), performed in our unit along
      ten years. PATIENTS AND METHODS: Starting from January 2005, 520 patients, 206
      men (39.6%) and 314 women (60.4%) were treated at our institution. Among patients
      candidate to bariatric surgery 145 underwent IB, 120 underwent LAGB, 175
      underwent LSG and 80 underwent LMGB. Follow up rate was 93.1% for IB at 6 months;
      74.1% and 48% for LAGB at 36 and 60 months respectively; 72.8% and 58.1% for LSG
      at 36 and 60 months respectively; and 84.2% for LMGB at 36 months. RESULTS: The
      period 2005-2014 has been considered. Mortality was 1/520 patients (0.19%). The
      excess weight loss rate (EWL%) has been 32.8 for IB at six months, 53.7 for LAGB
      and 68.1 for LSG, at 60 months respectively and 79.5 for LMGB at 36 months. Early
      major postoperative complications requiring surgery were 0.6% for IB and 1.1% for
      LSG whereas late major postoperative complications were 1.2% for IB, 4.1% for
      LAGB and 0.5% for LSG. Diabetes resolution rate was 0 for LAGB, 76.9% for LSG and
      80% for LMGB at 36 months. CONCLUSIONS: If more invasive procedures as LSG or
      LMGB may entail higher operative and peroperative risks, conversely, in skilled
      hands their efficacy remains undisputed, especially in the long term, presenting
      a very low rate of major complications. In general, the efficacy of a bariatric
      surgery unit seems improved by the capability to offer both different primary
      procedures and re-do surgery.

PMID- 24861546
TI  - DNA damage response and senescence in endothelial cells of human cerebral cortex
      and relation to Alzheimer's neuropathology progression: a population-based study
      in the Medical Research Council Cognitive Function and Ageing Study (MRC-CFAS)
      cohort.
AB  - AIMS: Abnormalities of the brain microvasculature in Alzheimer's disease have led
      to the vascular hypothesis of the disease, which predicts that vascular changes
      precede neuronal dysfunction and degeneration. To determine the spectrum of
      endothelial injury in the elderly and its relation to Alzheimer-type
      neuropathology we investigated DNA damage in a population-based sample derived
      from the Medical Research Council Cognitive Function and Ageing Study. METHODS:
      We examined endothelial damage in frontal and temporal cortex (n = 97) using
      immunohistochemistry for gammaH2AX and DNA-protein kinase (DNA-PKcs). To
      determine the effects of endothelial DNA damage at the earliest stages of
      Alzheimer's pathology we further focused our analysis on cases classified as
      Braak 0-II and examined endothelial senescence using histochemistry for beta
      galactosidase and the expression of genes related to DNA damage and senescence
      using quantitative polymerase chain reaction (qPCR). RESULTS: We demonstrated
      large variation in endothelial DNA damage which was not associated with
      Alzheimer's neuropathology. Endothelial DNA-PKcs correlated with neuronal and
      glial DNA-PKcs counts. Focusing our further analysis on Braak 0-II cases, qPCR
      analysis demonstrated a trend to increased TP53 (P = 0.064) in cases with high
      compared with low endothelial DNA damage which was supported by
      immunohistochemical analysis of p53. Endothelial beta-galactosidase expression
      was associated with increased neuronal (P = 0.033) and glial (P = 0.038), but not
      endothelial DNA-PKcs expression. CONCLUSIONS: Damage to brain endothelial cells
      occurs early in relation to, or independently of, Alzheimer pathology, and
      parallels that in neurones and glia. Endothelial DNA damage and senescence are a
      brain ageing process that may contribute to dysfunction of the neurovascular unit
      in some elderly individuals.

PMID- 24861547
TI  - Is glaucoma comprehension associated with psychological disturbance and vision
      related quality of life for patients with glaucoma? A cross-sectional study.
AB  - OBJECTIVE: To investigate whether understanding of glaucoma is associated with
      psychological disturbance and vision-related quality of life (QoL) in patients
      with glaucoma. DESIGN: A prospective, hospital-based, cross-sectional study.
      SETTING: Shanghai, China. PARTICIPANTS: Five hundred patients with glaucoma were
      included in the study. Participants were asked to complete the glaucoma
      comprehension questionnaire, the Hospital Anxiety and Depression Scale (HADS)
      questionnaire, and the 25-item National Eye Institute Visual Functioning
      Questionnaire (NEI VFQ-25). OUTCOME MEASURES: Sociodemographic data and clinical
      data were collected. Multivariate adjusted linear regression analyses were
      performed to examine factors related to psychological disorder and QoL. The
      relationship between understanding of glaucoma and psychological status or QoL
      was analysed. RESULTS: The mean age of patients was 56.5+/-17.2 years, and the
      mean duration of glaucoma was 4.6+/-6.3 years. About half (54.2%) of the patients
      had primary open angle glaucoma, 37.2% had primary angle closure glaucoma, and
      8.6% had secondary glaucoma. The total score and the subscores of knowledge of
      glaucoma, compliance and habits were all negatively correlated with the HADS
      Depression and HADS scores. For NEI VFQ-25, the total comprehension score was
      positively related to general vision, near activity, distance activity, social
      function, colour vision and the composite score. Habits had a significant
      influence on both HADS-Depression and the composite score of NEI VFQ-25.
      CONCLUSIONS: The level of understanding about glaucoma is an independent factor
      negatively associated with psychological disturbance and positively associated
      with QoL in patients with glaucoma. However, it is a subjective factor which can
      be regulated, so imparting knowledge about glaucoma and establishing appropriate
      habits might help patients alleviate psychological disturbance and enhance their
      QoL.

PMID- 24861548
TI  - Systematic review of universal school-based resilience interventions targeting
      adolescent tobacco, alcohol or illicit drug use: review protocol.
AB  - INTRODUCTION: Tobacco, alcohol and illicit drug use contribute significantly to
      global rates of morbidity and mortality. Despite evidence suggesting
      interventions designed to increase adolescent resilience may represent a means of
      reducing adolescent substance use, and schools providing a key opportunity to
      implement such interventions, existing systematic reviews assessing the
      effectiveness of school-based interventions targeting adolescent substance use
      have not examined this potential. METHODS AND ANALYSIS: The aim of the systematic
      review is to determine whether universal interventions focused on enhancing the
      resilience of adolescents are effective in reducing adolescent substance use.
      Eligible studies will: include participants 5-18 years of age; report tobacco
      use, alcohol consumption or illicit drug use as outcomes; and implement a school
      based intervention designed to promote internal (eg, self-esteem) and external
      (eg, school connectedness) resilience factors. Eligible study designs include
      randomised controlled trials, cluster randomised controlled trials, staggered
      enrolment trials, stepped wedged trials, quasi-randomised trials, quasi
      experimental trials, time series/interrupted time-series trials, preference
      trials, regression discontinuity trials and natural experiment studies with a
      parallel control group. A search strategy including criteria for participants,
      study design, outcome, setting and intervention will be implemented in various
      electronic databases and information sources. Two reviewers will independently
      screen studies to assess eligibility, as well as extract data from, and assess
      risk of bias of included studies. A third reviewer will resolve any
      discrepancies. Attempts will be made to quantify trial effects by meta-analysis.
      Binary outcomes will be pooled and effect size reported using ORs. For continuous
      data, effect size of trials will be reported using a mean difference where trial
      outcomes report the same outcome using a consistent measure, or standardised mean
      difference where trials report a comparable measure. Otherwise, trial outcomes
      will be described narratively. DISSEMINATION: Review findings will be
      disseminated via peer-reviewed journals and conferences.

PMID- 24861549
TI  - IMPOSE (IMProving Outcomes after Sepsis)-the effect of a multidisciplinary follow
      up service on health-related quality of life in patients postsepsis syndromes-a
      double-blinded randomised controlled trial: protocol.
AB  - INTRODUCTION: Patients post sepsis syndromes have a poor quality of life and a
      high rate of recurring illness or mortality. Follow-up clinics have been
      instituted for patients postgeneral intensive care but evidence is sparse, and
      there has been no clinic specifically for survivors of sepsis. The aim of this
      trial is to investigate if targeted screening and appropriate intervention to
      these patients can result in an improved quality of life (Short Form 36 health
      survey (SF36V.2)), decreased mortality in the first 12 months, decreased
      readmission to hospital and/or decreased use of health resources. METHODS AND
      ANALYSIS: 204 patients postsepsis syndromes will be randomised to one of the two
      groups. The intervention group will attend an outpatient clinic two monthly for 6
      months and receive screening and targeted intervention. The usual care group will
      remain under the care of their physician. To analyse the results, a baseline
      comparison will be carried out between each group. Generalised estimating
      equations will compare the SF36 domain scores between groups and across time
      points. Mortality will be compared between groups using a Cox proportional
      hazards (time until death) analysis. Time to first readmission will be compared
      between groups by a survival analysis. Healthcare costs will be compared between
      groups using a generalised linear model. Economic (health resource) evaluation
      will be a within-trial incremental cost utility analysis with a societal
      perspective. ETHICS AND DISSEMINATION: Ethical approval has been granted by the
      Royal Brisbane and Women's Hospital Human Research Ethics Committee (HREC;
      HREC/13/QRBW/17), The University of Queensland HREC (2013000543), Griffith
      University (RHS/08/14/HREC) and the Australian Government Department of Health
      (26/2013). The results of this study will be submitted to peer-reviewed intensive
      care journals and presented at national and international intensive care and/or
      rehabilitation conferences. TRIAL REGISTRATION NUMBER: Australian and New Zealand
      Clinical Trials Registry ACTRN12613000528752.

PMID- 24861550
TI  - Preventive health services implemented by family physicians in Portugal-a cross
      sectional study based on two clinical scenarios.
AB  - OBJECTIVES: To assess whether Portuguese family physicians perform preventive
      health services in accordance with scientific evidence, based on the
      recommendations of the United States Preventive Services Task Force (USPSTF).
      DESIGN: Cross-sectional study. SETTING: Primary healthcare, Portuguese National
      Health Service. PARTICIPANTS: 255 Portuguese family physicians selected by a
      stratified cluster sampling design were invited to participate in a computer
      assisted telephone survey. OUTCOMES: Prevalence of compliance with USPSTF
      recommendations for screening, given a male and female clinical scenario and a
      set of proposed medical interventions, including frequency of the intervention
      and performance in their own daily practice. RESULTS: A response rate of 95.7%
      was obtained (n=244). 98-100% of family physicians answered according to the
      USPSTF recommendations in most interventions. In the male scenario, the lowest
      concordance was observed in the evaluation of prostate-specific antigen with 37%
      of family physicians answering according to the USPSTF recommendations. In the
      female scenario, the lowest concordance was for cholesterol testing with 2% of
      family physicians complying. Family physicians younger than 50 years had
      significantly better compliance scores than older ones (mean 77% vs 72%;
      p<0.001). CONCLUSIONS: We found a high degree of agreement with USPSTF
      recommendations among Portuguese family physicians. However, we also found
      results suggesting excessive use of some medical interventions, raising concerns
      related to possible harm associated with overdiagnosis and overtreatment.

PMID- 24861551
TI  - DUX4-induced gene expression is the major molecular signature in FSHD skeletal
      muscle.
AB  - Facioscapulohumeral dystrophy (FSHD) is caused by decreased epigenetic repression
      of the D4Z4 macrosatellite array and recent studies have shown that this results
      in the expression of low levels of the DUX4 mRNA in skeletal muscle. Several
      other mechanisms have been suggested for FSHD pathophysiology and it remains
      unknown whether DUX4 expression can account for most of the molecular changes
      seen in FSHD. Since DUX4 is a transcription factor, we used RNA-seq to measure
      gene expression in muscle cells transduced with DUX4, and in muscle cells and
      biopsies from control and FSHD individuals. We show that DUX4 target gene
      expression is the major molecular signature in FSHD muscle together with a gene
      expression signature consistent with an immune cell infiltration. In addition,
      one unaffected individual without a known FSHD-causing mutation showed the
      expression of DUX4 target genes. This individual has a sibling with FSHD and also
      without a known FSHD-causing mutation, suggesting the presence of an unidentified
      modifier locus for DUX4 expression and FSHD. These findings demonstrate that the
      expression of DUX4 accounts for the majority of the gene expression changes in
      FSHD skeletal muscle together with an immune cell infiltration. 

PMID- 24861552
TI  - Genome-wide association study yields variants at 20p12.2 that associate with
      urinary bladder cancer.
AB  - Genome-wide association studies (GWAS) of urinary bladder cancer (UBC) have
      yielded common variants at 12 loci that associate with risk of the disease. We
      report here the results of a GWAS of UBC including 1670 UBC cases and 90 180
      controls, followed by replication analysis in additional 5266 UBC cases and 10
      456 controls. We tested a dataset containing 34.2 million variants, generated by
      imputation based on whole-genome sequencing of 2230 Icelanders. Several
      correlated variants at 20p12, represented by rs62185668, show genome-wide
      significant association with UBC after combining discovery and replication
      results (OR = 1.19, P = 1.5 * 10(-11) for rs62185668-A, minor allele frequency =
      23.6%). The variants are located in a non-coding region approximately 300 kb
      upstream from the JAG1 gene, an important component of the Notch signaling
      pathways that may be oncogenic or tumor suppressive in several forms of cancer.
      Our results add to the growing number of UBC risk variants discovered through
      GWAS. 

PMID- 24861555
TI  - Influence of lithium doping on the thermodynamic properties of graphene based
      superconductors.
AB  - The superconducting phase in graphene can be induced by doping its surface with
      lithium atoms. In this paper, it is shown that the critical temperature (TC) for
      the LiC6 and Li2C6 compounds changes from 8.55 K to 21.83 K. The other
      thermodynamic parameters--the order parameter (Delta), the specific heat for the
      superconducting (C(S)) and the normal (C(N)) state and the thermodynamic critical
      field (HC)--differ from the predictions of the Bardeen-Cooper-Schrieffer theory.
      In particular, the ratio RDelta = 2Delta(0)/kBTC is equal to[3.72]LiC6 and
      [4.21]Li2C6. Additionally, the quantities RC = DeltaC(TC)/C(N)(TC) and [Formula:
      see text] take the values[1.47]LiC6,[1.79]Li2C6 and [0.167]LiC6, [0.144]Li2C6.
      Finally, it is shown that the electron effective mass at TC is high and
      equals:[1.61me]LiC6 and [2.12me]Li2C6.

PMID- 24861554
TI  - Maximizing protection from use of oral cholera vaccines in developing country
      settings: an immunological review of oral cholera vaccines.
AB  - When oral vaccines are administered to children in lower- and middle-income
      countries, they do not induce the same immune responses as they do in developed
      countries. Although not completely understood, reasons for this finding include
      maternal antibody interference, mucosal pathology secondary to infection,
      malnutrition, enteropathy, and previous exposure to the organism (or related
      organisms). Young children experience a high burden of cholera infection, which
      can lead to severe acute dehydrating diarrhea and substantial mortality and
      morbidity. Oral cholera vaccines show variations in their duration of protection
      and efficacy between children and adults. Evaluating innate and memory immune
      response is necessary to understand V. cholerae immunity and to improve current
      cholera vaccine candidates, especially in young children. Further research on the
      benefits of supplementary interventions and delivery schedules may also improve
      immunization strategies.

PMID- 24861556
TI  - First-trimester exposure to metformin and risk of birth defects: a systematic
      review and meta-analysis.
AB  - BACKGROUND: Metformin is generally considered a non-teratogenic drug; however,
      only a few studies specifically designed to assess the rate of congenital
      anomalies after metformin use have been published in the literature. The objects
      of the present study were to review all of the prospective and retrospective
      studies reporting on women treated with metformin at least during the first
      trimester of their pregnancy and to estimate the overall rate of major birth
      defects. METHODS: Databases were searched for English language articles until
      December 2013. Inclusion criteria for the meta-analysis were: a case group of
      women with PCOS or pre-pregnancy type 2 diabetes and first-trimester exposure to
      metformin; a disease-matched control group which was not exposed to metformin or
      other oral anti-diabetic agents; and a list of the major anomalies in both the
      study and the control groups. A random effects model was used for the meta
      analysis of data, using odds ratios. Studies not fulfilling the inclusion
      criteria for the meta-analysis but reporting relevant data on major malformations
      in women diagnosed with PCOS were then used to estimate the overall birth defects
      rate. RESULTS: Meta-analysis of nine controlled studies with women affected by
      PCOS detected that the rate of major birth defects in the metformin-exposed group
      was not statistically increased compared with the disease-matched control group
      and that there was no significant heterogeneity among the studies. The metformin
      exposed sample was composed of 351 pregnancies and the OR of major birth defects
      was 0.86 (95% confidence interval: 0.18-4.08; Pheterogeneity = 0.71). By
      evaluating all of the non-overlapping PCOS studies reported in the literature,
      even those without an appropriate control group, the overall rate of major
      anomalies was 0.6% in the sample of 517 women who discontinued the therapy upon
      conception or confirmation of pregnancy and 0.5% in the sample of 634 women who
      were treated with metformin throughout the first trimester of their pregnancy.
      Regarding type 2 diabetic women, we did not identify a sufficient number of
      studies with metformin exposure during the first trimester to proceed with the
      meta-analysis. CONCLUSIONS: There is currently no evidence that metformin is
      associated with an increased risk of major birth defects in women affected by
      PCOS and treated during the first trimester. However larger ad hoc studies are
      warranted in order to definitely confirm the safety and efficacy of this drug in
      pregnancy.

PMID- 24861557
TI  - Improvement in the quality of abstracts in major clinical journals since CONSORT
      extension for abstracts: a systematic review.
AB  - BACKGROUND: We sought to determine if the publication of the Consolidated
      Standards of Reporting Trials (CONSORT)(1) extension for abstracts in 2008 had
      led to an improvement in reporting abstracts of randomized controlled trials
      (RCTs).(2) METHODS: We searched PubMed for RCTs published in 2007 and 2012 in top
      tier general medicine journals. A random selection of 100 trial abstracts was
      obtained for each year. Data were extracted in duplicate on the adherence to the
      CONSORT extension for abstracts. The primary outcome was the mean number of items
      reported and the secondary outcome was the odds of reporting each item. We also
      estimated incidence rate ratios (IRRs).(3) RESULTS: Significantly more checklist
      items were reported in 2012 than in 2007: adjusted mean difference was 2.91 (95%
      confidence interval [CI](4) 2.35, 3.41; p<0.001). In 2012 there were significant
      improvements in reporting the study as randomized in the title, describing the
      trial design, the participants, and objectives and blinding. In the Results
      section, trial status and numbers analyzed were also reported better. The IRRs
      were significantly higher for 2012 (IRR 1.32; 95% CI 1.25, 1.39; p<0.001) and in
      multisite studies compared to single site studies (IRR 1.08; 95% CI 1.03, 1.15;
      p=0.006). CONCLUSIONS: There was a significant improvement in the reporting of
      abstracts of RCTs in 2012 compared to 2007. However, there is still room for
      improvement as some items remain under-reported.

PMID- 24861558
TI  - Flexible and extended dosing of nicotine replacement therapy or varenicline in
      comparison to fixed dose nicotine replacement therapy for smoking cessation:
      rationale, methods and participant characteristics of the FLEX trial.
AB  - Quitting smoking is the single most effective strategy to reduce morbidity and
      premature mortality in smokers. Research has demonstrated the effectiveness of
      pharmacotherapy in smoking cessation, but few studies have directly compared
      varenicline and monotherapy nicotine replacement therapy (NRT) and none have
      examined varenicline and combinations of NRT products. The majority of smoking
      cessation trials involve carefully circumscribed populations, making their
      results less generalizable to those with severe medical conditions or psychiatric
      comorbidities. This paper reports on the rationale, methodology and participant
      characteristics of a randomized controlled trial designed to: (1) determine which
      pharmacotherapy - NRT, long term combinations of NRT, or varenicline - is most
      effective in achieving abstinence; (2) investigate the incidence of
      neuropsychiatric symptoms among participants over the course of their quit
      attempt; and (3) assess whether there is a significant difference in the
      incidence of neuropsychiatric symptoms in those receiving differing
      pharmacotherapies, and between those with and without psychiatric illnesses. The
      primary outcome was carbon monoxide confirmed abstinence from weeks 5-52
      following a target quit date. Secondary outcomes included neuropsychiatric (i.e.,
      depression, suicidal ideation, anxiety, anger) and withdrawal symptoms. Smokers
      (N=737) were randomly assigned to one of three treatment conditions, and were
      scheduled to attend 8 follow-up appointments over 12 months. All participants
      received 6-15 minute practical counseling sessions with nurse counselors
      experienced in treating tobacco dependence. We expect that the results will lead
      to an enhanced understanding of the efficacy of these pharmacotherapies,
      including those with a history of psychiatric illness.

PMID- 24861559
TI  - A pilot 'window of opportunity' neoadjuvant study of metformin in localised
      prostate cancer.
AB  - BACKGROUND: Metformin is an inhibitor of complex 1 in the respiratory chain, and
      is widely used to reduce insulin resistance. It has also been described to have
      pleotropic effects including via AMPK on inhibiting the mTOR kinase. Pre-clinical
      and epidemiological studies suggest an ability to modulate disease evolution in
      prostate cancer. In this study, we aimed to (i) demonstrate safety and
      tolerability of neoadjuvant metformin administration and (ii) document changes in
      proliferative (Ki67) and AMPK-related signalling indices between matching
      biopsies and prostatectomies METHODS: Men were treated in a single-arm 'window of
      opportunity' study between their decision to undergo radical prostatectomy and
      the operation itself. Forty patients were planned but only 24 patients were
      enrolled owing to slow accrual. Twenty-one patients were evaluable for
      pathological outcomes and 22 for serum metabolic indices. Metformin was given at
      doses to 500 mg t.i.d. Ki67 index was calculated using the Aperio-positive pixel
      count algorithm, whereas immunohistochemical measurements were by consensus H
      Score. Comparative statistics were analysed by students t-tests and/or Wilcoxon
      matched pairs signed rank test. RESULTS: Baseline characteristics included median
      PSA 6 ng ml(-1) (3.22-36.11 ng ml(-1)). Median duration of drug treatment was 41
      days (18-81). Treatment was well tolerated with only three patients developing
      G3/4 toxicities. In a per patient and per tumour analyses, metformin reduced the
      Ki67 index by relative amounts of 29.5 and 28.6 % (P=0.0064 and P=0.0042)
      respectively. There was also a significant decrease in P-4EBP1 staining (P<0.001)
      but no change in P-AMPK or P-ACC. There were no correlations between any
      metabolic, morphometric or cancer-related serum indices. There was a trend
      towards PSA reduction (P=0.08). The study is limited by small patient numbers and
      tumour heterogeneity. CONCLUSIONS: Neoadjuvant metformin is well tolerated prior
      to radical prostatectomy. Data to date indicate promising effects on metabolic
      and tissue proliferation and signalling parameters.

PMID- 24861560
TI  - Stability of end-of-life preferences: a systematic review of the evidence.
AB  - IMPORTANCE: Policies and practices that promote advance care planning and advance
      directive completion implicitly assume that patients' choices for end-of-life
      (EOL) care are stable over time, even with changes in health status. OBJECTIVE:
      To systematically evaluate the evidence on the stability of EOL preferences over
      time and with changes in health status. EVIDENCE REVIEW: We searched for
      longitudinal studies of patients' preferences for EOL care in PubMed, EMBASE, and
      using citation review. Studies restricted to preferences regarding the place of
      care at the EOL were excluded. FINDINGS: A total of 296 articles were assessed
      for eligibility, and 59 met inclusion criteria. Twenty-four articles had
      sufficient data to extract or calculate the percentage of individuals with stable
      preferences or the percentage of total preferences that were stable over time. In
      17 studies (71%) more than 70% of patients' preferences for EOL care were stable
      over time. Preference stability was generally greater among inpatients and
      seriously ill outpatients than among older adults without serious illnesses (P <
      .002). Patients with higher education and who had engaged in advance care
      planning had greater preference stability, and preferences to forgo therapies
      were generally more stable than preferences to receive therapies. Among 9 of the
      24 studies (38%) assessing changes in health status, no consistent relationship
      with preference changes was identified. CONCLUSIONS AND RELEVANCE: Considerable
      variability among studies in the methods of preference assessment, the time
      between assessments, and the definitions of stability preclude meta-analytic
      estimates of the stability of patients' preferences and the factors influencing
      these preferences. Although more seriously ill patients and those who engage in
      advance care planning most commonly have stable preferences for future
      treatments, further research in real-world settings is needed to confirm the
      utility of advance care plans for future decision making.

PMID- 24861553
TI  - Meta-analysis of genome-wide association studies in East Asian-ancestry
      populations identifies four new loci for body mass index.
AB  - Recent genetic association studies have identified 55 genetic loci associated
      with obesity or body mass index (BMI). The vast majority, 51 loci, however, were
      identified in European-ancestry populations. We conducted a meta-analysis of
      associations between BMI and ~2.5 million genotyped or imputed single nucleotide
      polymorphisms among 86 757 individuals of Asian ancestry, followed by in silico
      and de novo replication among 7488-47 352 additional Asian-ancestry individuals.
      We identified four novel BMI-associated loci near the KCNQ1 (rs2237892, P = 9.29
      * 10(-13)), ALDH2/MYL2 (rs671, P = 3.40 * 10(-11); rs12229654, P = 4.56 * 10(
      9)), ITIH4 (rs2535633, P = 1.77 * 10(-10)) and NT5C2 (rs11191580, P = 3.83 * 10(
      8)) genes. The association of BMI with rs2237892, rs671 and rs12229654 was
      significantly stronger among men than among women. Of the 51 BMI-associated loci
      initially identified in European-ancestry populations, we confirmed eight loci at
      the genome-wide significance level (P < 5.0 * 10(-8)) and an additional 14 at P <
      1.0 * 10(-3) with the same direction of effect as reported previously. Findings
      from this analysis expand our knowledge of the genetic basis of obesity. 

PMID- 24861561
TI  - Morphine stimulates cancer progression and mast cell activation and impairs
      survival in transgenic mice with breast cancer.
AB  - BACKGROUND: Morphine stimulates angiogenesis and cancer progression in mice. We
      investigated whether morphine influences tumour onset, development, and animal
      model survival, and whether u-opioid receptor (MOR), lymphangiogenesis, mast cell
      activation, and substance P (SP) are associated with the tumour-promoting effects
      of morphine. METHODS: Transgenic mice with a rat C3(1) simian virus 40 large
      tumour antigen fusion gene which demonstrate the developmental spectrum of human
      infiltrating ductal breast carcinoma were used. Mice were treated at different
      ages with clinically relevant doses of morphine or phosphate-buffered saline to
      determine the effect on tumour development and progression, and on mouse
      survival. Tumours were analysed for MOR, angiogenesis, lymphangiogenesis, SP, and
      mast cell activation by immunofluorescent- or laser scanning confocal-microscopy.
      Cytokine and SP levels were determined by enzyme-linked immunosorbent assay.
      RESULTS: Morphine did not influence tumour development when given before the
      onset of tumour appearance, but significantly promoted progression of established
      tumours, and reduced survival. MOR-immunoreactivity (ir) was observed in larger
      but not in smaller tumours. Morphine treatment resulted in increased tumour
      angiogenesis, peri-tumoural lymphangiogenesis, mast cell activation, and higher
      levels of cytokines and SP in tumours. SP-ir co-localized with mast cells and
      elsewhere in the tumours. CONCLUSIONS: Morphine does not affect the onset of
      tumour development, but it promotes growth of existing tumours, and reduces
      overall survival in mice. MOR may be associated with morphine-induced cancer
      progression, resulting in shorter survival. Mast cell activation by morphine may
      contribute to increased cytokine and SP levels, leading to cancer progression and
      refractory pain.

PMID- 24861564
TI  - Quantitation of reflux and outflow obstruction in patients with CVD and
      correlation with clinical severity.
AB  - AIM: Chronic venous disease (CVD) is the result of venous reflux, obstruction or
      a combination of both. So far, attempts to correlate venous hemodynamic
      measurements with symptoms and signs of CVD have produced poor to moderate
      results, probably because of lack of methods to quantitate obstruction and
      combine measurements of reflux and obstruction. Our hypothesis is that the
      combination of quantitative measurements of (a) overall reflux (superficial and
      deep) and (b) overall outflow resistance i.e. including the collateral
      circulation would provide a hemodynamic index that should be related to the
      severity of the disease. METHODS: Twenty-five limbs with chronic venous disease
      and 1 limb from a healthy volunteer (VCSS 0-13) were studied. The clinical CEAP
      classification was C0 in one limb, C1 in 2 limbs, C2 in 10 limbs, C3 in 3 limbs,
      C4 in 1 limb, C5 in 6 limbs and C6 in 3 limbs. Air-plethysmography was used to
      measure reflux (VFI in mL/s) when the subject changed position from horizontal to
      standing. Subsequently, with the subject horizontal and the foot elevated 15 cm,
      simultaneous recordings of pressure and volume were made on release of a proximal
      thigh cuff inflated to 70 mmHg. Pressure change was recorded with a needle in the
      foot and volume change with air-plethysmography. Flow (Q in mL/min) was
      calculated at intervals of 0.1 seconds from tangents on the volume outflow curve.
      Outflow resistance (R) was calculated at 0.1 second intervals by dividing
      pressure by the corresponding flow (R=P/Q). R increased markedly at pressures
      lower than 25 mmHg due to decrease in vein cross-sectional area, so resistance at
      25 mmHg (R25) was used in this study. RESULTS: In a multivariable linear
      regression analysis with VCSS as the dependent variable, both VFI and R25 were
      independent predictors (P<0.001). Using the constant (0.595) and regression
      coefficients, the regression equation provided a Hemodynamic Index (HI) or
      estimated VCSS=0.595 + (VFI x 0.41) + (R25 x 98). Thus, HI could be calculated
      for every patient by substituting VFI and R25 in the equation. HI or calculated
      VCSS was linearly related to the observed VCSS (r=0.86). CONCLUSION: The results
      indicate that the combination of quantitative measurements of reflux and outflow
      resistance provide a hemodynamic index which is linearly related to the VCSS.
      These findings need to be confirmed in larger series.

PMID- 24861563
TI  - Reliability of SleepStrip as a screening test in obstructive sleep apnea
      patients.
AB  - Obstructive sleep apnea syndrome (OSAS) is a common sleep disorder and related to
      multiple conditions that cause mortality in adults. In the present study,
      reliability of SleepStrip, a disposable screening device for detection of OSAS,
      is tested. In this prospective, nonrandomized double-blinded single cohort study
      at an academic health center, the performance of the SleepStrip in detecting
      respiratory events and establishing an SleepStrip score (Sscore) in domestic use
      were compared to the apnea-hypopnea index (AHI) obtained by the standard
      polysomnography (PSG) recordings in the sleep laboratory. Forty-one patients who
      have the PSG results participated the study and wore the SleepStrips at home.
      Test efficiency rate was 75% and there was a positive correlation between PSG-AHI
      scores and Sscores (r = 0.71, p < 0.001). However, diagnostic accuracy analysis
      showed that the correlation between Sscores and PSG-AHI scores were significant
      only at AHI > 30 levels. The SleepStrip has 100% specificity and positive
      predictive values, but it also has low negative predictive and sensitivity
      values. The SleepStrip is not a reliable screening test in differential diagnosis
      among simple snorers, mild, moderate and severe OSAS patients. However, high
      Sscores highly indicate the presence of moderate-severe OSAS. We can safely send
      these patients to split-night PSG and continuous, automatic, bi-level positive
      airway pressure (CPAP/BPAP/APAP) titration at the same night. The SleepStrip may
      increase the effective use of the sleep laboratories.

PMID- 24861562
TI  - Phylogenetic diversity of a microbialite reef in a cold alkaline freshwater lake.
AB  - A culture-independent multidomain survey of biodiversity in microbialite
      structures within the cold alkaline Pavilion Lake (British Columbia, Canada)
      revealed a largely homogenous community at depths from 10 to 30 m. Real-time
      quantitative PCR was used to demonstrate that bacteria comprised approximately
      80%-95% of recoverable phylotypes. Archaeal phylotypes accounted for <5% of the
      community in microbialites exposed to the water column, while structures in
      sediment contact supported 4- to 5-fold higher archaeal abundance. Eukaryal
      phylotypes were rare and indicated common aquatic diatoms that were concluded not
      to be part of the microbialite community. Phylogenetic analysis of rRNA genes
      from clone libraries (N = 491) revealed that alphaproteobacterial phylotypes were
      most abundant. Cyanobacterial phylotypes were highly diverse but resolved into 4
      dominant genera: Acaryochloris, Leptolyngbya, Microcoleus, and Pseudanabaena.
      Interestingly, microbialite cyanobacteria generally affiliated phylogenetically
      with aquatic and coral cyanobacterial groups rather than those from
      stromatolites. Other commonly encountered bacterial phylotypes were from members
      of the Acidobacteria, with relatively low abundance of the Betaproteobacteria,
      Chloroflexi, Nitrospirae, and Planctomycetes. Archaeal diversity (N = 53) was
      largely accounted for by Euryarchaeota, with most phylotypes affiliated with
      freshwater methanogenic taxa. 

PMID- 24861565
TI  - The dual blocker of FAAH/TRPV1 N-arachidonoylserotonin reverses the behavioral
      despair induced by stress in rats and modulates the HPA-axis.
AB  - In recent years, several studies have explored the involvement of the
      deregulation of the hypothalamus-pituitary-adrenal (HPA) axis in the
      pathophysiology of stress-related disorders. HPA hyper-activation as a
      consequence of acute/chronic stress has been found to play a major role in the
      neurobiological changes that are responsible for the onset of such states.
      Currently available medications for depression, one of the most relevant stress
      related disorders, present several limitations, including a time lag for
      treatment response and low rates of efficacy. N-Arachidonoylserotonin (AA-5-HT),
      a dual blocker at fatty acid amide hydrolase (FAAH, the enzyme responsible for
      the inactivation of the endocannabinoid anandamide) and transient receptor
      potential vanilloid type-1 channel (TRPV1), produces anxiolytic-like effects in
      mice. The present study was designed to assess the capability of AA-5-HT to
      reverse the behavioral despair following exposure to stress in rats and the role
      of the HPA-axis. Behavioral tasks were performed, and corticosterone and
      endocannabinoid (anandamide and 2-arachidonoylglycerol) levels were measured in
      selected brain areas critically involved in the pathophysiology of stress-related
      disorders (medial PFC and hippocampus) under basal and stress conditions, and in
      response to treatment with AA-5-HT. Our data show that AA-5-HT reverses the rat
      behavioral despair in the forced swim test under stress conditions, and this
      effect is associated with the normalization of the HPA-axis deregulation that
      follows stress application and only in part with elevation of anandamide levels.
      Blockade of FAAH and TRPV1 may thus represent a novel target to design novel
      therapeutic strategies for the treatment of stress-related disorders. 

PMID- 24861568
TI  - Direct X-ray observation of trapped CO2 in a predesigned porphyrinic metal
      organic framework.
AB  - Metal-organic frameworks (MOFs) are emerging microporous materials that are
      promising for capture and sequestration of CO2 due to their tailorable binding
      properties. However, it remains a grand challenge to pre-design a MOF with a
      precise, multivalent binding environment at the molecular level to enhance CO2
      capture. Here, we report the design, synthesis, and direct X-ray crystallographic
      observation of a porphyrinic MOF, UNLPF-2, that contains CO2-specific single
      molecular traps. Assembled from an octatopic porphyrin ligand with [Co2(COO)4]
      paddlewheel clusters, UNLPF-2 provides an appropriate distance between the
      coordinatively unsaturated metal centers, which serve as the ideal binding sites
      for in situ generated CO2. The coordination of Co(II) in the porphyrin macrocycle
      is crucial and responsible for the formation of the required topology to trap
      CO2. By repeatedly releasing and recapturing CO2, UNLPL-2 also exhibits
      recyclability.

PMID- 24861566
TI  - Classical and pleiotropic actions of dipyridamole: Not enough light to illuminate
      the dark tunnel?
AB  - Dipyridamole is a platelet inhibitor indicated for the secondary prevention of
      transient ischemic attack. It inhibits the enzyme phosphodiesterase, elevates
      cAMP and cGMP levels and prevents platelet aggregation. Dipyridamole inhibits the
      cellular uptake of adenosine into red blood cells, platelets and endothelial
      cells that results in increased extracellular availability of adenosine, leading
      to modulation of cardiovascular function. The antiplatelet action of dipyridamole
      might offer therapeutic benefits in secondary stroke prevention in combination
      with aspirin. Inflammation and oxidative stress play an important role in
      atherosclerosis and thrombosis development, leading to stroke progression.
      Studies demonstrated anti-inflammatory, anti-oxidant and anti-proliferative
      actions of dipyridamole. These pleiotropic potentials of dipyridamole might
      contribute to improved therapeutic outcomes when used with aspirin in preventing
      secondary stroke. Dipyridamole was documented as a coronary vasodilator 5 decades
      ago. The therapeutic failure of dipyridamole as a coronary vasodilator is linked
      with induction of 'coronary steal' phenomenon in which by dilating resistance
      vessels in non-ischemic zone, dipyridamole diverts the already reduced blood flow
      away from the area of ischemic myocardium. Dipyridamole at high-dose could cause
      a marked 'coronary steal' effect. Dipyridamole, however, at low-dose could have a
      minimal hemodynamic effect. Low-dose dipyridamole treatment has a therapeutic
      potential in partially preventing diabetes mellitus-induced experimental vascular
      endothelial and renal abnormalities by enhancing endothelial nitric oxide signals
      and inducing renovascular reduction of oxidative stress. In spite of plenteous
      research on dipyridamole's use in clinics, its precise clinical application is
      still obscure. This review sheds lights on pleiotropic pharmacological actions
      and therapeutic potentials of dipyridamole. 

PMID- 24861567
TI  - Intracellular light-activation of riboswitch activity.
AB  - By combining a riboswitch with a cell-permeable photocaged small-molecule ligand,
      an optochemical gene control element was constructed that enabled spatial and
      temporal control of gene expression in bacterial cells. The simplicity of this
      strategy, coupled with the ability to create synthetic riboswitches with tailored
      ligand specificities and output in a variety of microorganisms, plants, and fungi
      might afford a general strategy to photocontrol gene expression in vivo. The
      ability to activate riboswitches by using light enables the interrogation and
      manipulation of a wide range of biological processes with high precision, and
      will have broad utility in the regulation of artificial genetic circuits.

PMID- 24861569
TI  - Observation of the full exciton and phonon fine structure in CdSe/CdS dot-in-rod
      heteronanocrystals.
AB  - Light emission of semiconductor nanocrystals is a complex process, depending on
      many factors, among which are the quantum mechanical size confinement of excitons
      (coupled electron-hole pairs) and the influence of confined phonon modes and the
      nanocrystal surface. Despite years of research, the nature of nanocrystal
      emission at low temperatures is still under debate. Here we unravel the different
      optical recombination pathways of CdSe/CdS dot-in-rod systems that show an
      unprecedented number of narrow emission lines upon resonant laser excitation. By
      using self-assembled, vertically aligned rods and application of
      crystallographically oriented high magnetic fields, the origin of all these peaks
      is established. We observe a clear signature of an acoustic-phonon assisted
      transition, separated from the zero-phonon emission and optical-phonon replica,
      proving that nanocrystal light emission results from an intricate interplay
      between bright (optically allowed) and dark (optically forbidden) exciton states,
      coupled to both acoustic and optical phonon modes. 

PMID- 24861570
TI  - A cell-based biosensor system HepG2CDKN1A-DsRed for rapid and simple detection of
      genotoxic agents.
AB  - The regulatory requirements for genotoxicity testing rely on a battery of
      genotoxicity tests, which generally consist of bacterial and mammalian cell
      assays for detection of gene mutations and chromosomal aberrations. However, for
      rapid screening, these methods are not appropriate. We have developed a new cell
      based biosensor system that provides rapid and simple detection of genotoxic
      substances. This is based on stable transfection of human hepatoma HepG2 cells
      with a plasmid that encodes the red fluorescent protein DsRed2 under the control
      of the CDKN1A promoter (HepG2CDKN1A-DsRed cells). As the major downstream target
      gene of activated TP53, the tumour-suppressor gene CDKN1A is responsible for cell
      cycle arrest following DNA damage, and it has been shown to be specifically up
      regulated by genotoxic carcinogens. The assay is optimised for a 96-well
      microplate format and spectrofluorimetric quantification of induced DsRed
      expression. The assay was evaluated by testing direct-acting and indirect-acting
      genotoxic compounds with different mechanisms of action, along with non-genotoxic
      compounds. Out of 25 compounds that are known to be genotoxic in vitro and in
      vivo, 21 (84%) are detected as positive at non-cytotoxic doses, whereas of 12
      compounds not considered genotoxic, 11 (92%) are negative. These data indicate
      the high sensitivity and specificity of our biosensor system. Based on its
      simplicity and sensitivity, this biosensor developed with HepG2CDKN1A-DsRed cells
      has the potential to become a valuable tool for genotoxicity screening for
      chemical safety evaluation, as well as for environmental and occupational
      monitoring of exposure to genotoxic agents and their complex mixtures. 

PMID- 24861571
TI  - A device design of an integrated CMOS poly-silicon biosensor-on-chip to enhance
      performance of biomolecular analytes in serum samples.
AB  - For on-site clinical diagnosis of biomolecules, the detection performances of
      most point-of-care (POC) biosensor devices are limited by undesired cross
      detection of other non-analyte proteins in patient serum samples and other
      complex samples. To conquer this obstacle, this work presents a fully integrated
      bottom-gate poly-silcion nanowire (polySi NW) biosensor system-on-chip (SoC) to
      enhance the detection performance of cardiac-specific troponin-I (cTnI)
      concentration levels in serum samples. By applying proper electrical potential at
      the bottom gate under polySi NW biosensor, the biosensor response to cTnI
      biomarker can be improved by at least 16 fold in 50% phantom serum samples. The
      experimental result shows its detection range is from 3.2 * 10(-13)M(mol l(-1))
      to 3.2 * 10(-10)M. This enhancement can be attributed to the electrostatic
      interactions between target biomolecules and voltage-applied bottom gate
      electrodes. This is the first time that a polySi NW CMOS biosensor chip has shown
      feasibilities to detect specific biomarkers in serum samples. Therefore, the
      developed technology paves the way toward on-field applications of CMOS
      compatible SiNW biosensing technologies and it can be employed for future
      biomolecular analysis in on-site serum diagnosis applications.

PMID- 24861573
TI  - Candida glabrata: a deadly companion?
AB  - The yeast Candida glabrata has become a major fungal opportunistic pathogen of
      humans since the 1980s. Contrary to what its name suggests, it is much closer,
      phylogenetically, to the model yeast Saccharomyces cerevisiae than to the most
      prevalent human fungal pathogen, Candida albicans. Its similarity to S.
      cerevisiae fortunately extends to their amenability to molecular genetics
      methods. C. glabrata is now described as part of the Nakaseomyces clade, which
      includes two new pathogens and other environmental species. C. glabrata is likely
      a commensal species of the human digestive tract, but systemic infections of
      immunocompromised patients are often fatal. In addition to being the subject of
      active medical research, other studies on C. glabrata focus on fundamental
      aspects of evolution of yeast genomes and adaptation. For example, the genome of
      C. glabrata has undergone major gene and intron loss compared to S. cerevisiae.
      It is also an apparently asexual species, a feature that inevitably leads to
      questions about the species' evolutionary past, present and future. On-going
      research with this yeast continues to address various aspects of adaptation to
      the human host and mechanisms of evolution in the Saccharomycetaceae, major model
      organisms for biology.

PMID- 24861572
TI  - Organophosphate vapor detection on gold electrodes using peptide nanotubes.
AB  - Peptide nanotubes (PNTs) encapsulating horseradish peroxidase and surface coated
      with acetylcholinesterase (AChE) were attached to gold screen printed electrodes
      to construct a novel gas phase organophosphate (OP) biosensor. When the sensor
      with the AChE enzyme is put in contact with acetylthiocholine (ATCh), the ATCh is
      hydrolyzed to produce thiocholine, which is then oxidized by horseradish
      peroxidase (HRP). Direct electron transfer between HRP and electrode is achieved
      through PNTs. The signal produced by the electron transfer is measured with
      cyclic voltammetry (CV). The presence of an OP compound inhibits this signal by
      binding with the AChE enzyme. In this study, gas phase malathion was used as a
      model OP due to the fact that it displays the identical binding mechanism with
      acetylcholinesterase (AChE) as its more potent counterparts such as sarin and VX,
      but has low toxicity, making it more practical and safer to handle. The CV signal
      was proportionally inhibited by malathion vapor concentrations as low as 12 ppbv.
      Depending on the method used in their preparation, the electrodes maintained
      their activity for up to 45 days. This research demonstrates the potential of
      applying nano-modified biosensors for the detection of low levels of OP vapor, an
      important development in countering weaponized organophosphate nerve agents and
      detecting commercially-used OP pesticides.

PMID- 24861574
TI  - Regulation of apoptosis by heat shock proteins.
AB  - Thermotolerance, the acquired resistance of cells to stress, is a well
      established phenomenon. Studies of the key mediators of this response, the heat
      shock proteins (HSPs), have led to the discovery of the important roles played by
      these proteins in the regulation of apoptotic cell death. Apoptosis is critical
      for normal tissue homeostasis and is involved in diverse processes including
      development and immune clearance. Apoptosis is tightly regulated by both
      proapoptotic and antiapoptotic factors, and dysregulation of apoptosis plays a
      significant role in the pathophysiology of many diseases. In the recent years,
      HSPs have been identified as key determinants of cell survival, which can
      modulate apoptosis by directly interacting with components of the apoptotic
      machinery. Therefore, manipulation of the HSPs could represent a viable strategy
      for the treatment of diseases. Here, we review the current knowledge with regard
      to the mechanisms of HSP-mediated regulation of apoptosis.

PMID- 24861576
TI  - Involvement of Trichoderma asperellum strain T6 in regulating iron acquisition in
      plants.
AB  - Iron (Fe) deficiency is a major plant nutritional disorder in many parts of the
      world, particularly in areas with saline soils. Among the numerous root
      associated microbes that are beneficial for plant nutrient uptake, Trichoderma
      spp. are the most effective rhizosphere fungi for enhancing plant growth and
      plant resistance to biotic and abiotic stresses. To investigate the potential
      mechanisms of action of Trichoderma on insoluble Fe in the soil, which is
      difficult for plants to absorb and utilize, a high siderophore-producing strain
      of Trichoderma T6, was isolated from the rhizosphere of cucumber plants. The
      strain was identified as T. asperellum based on the morphological features and
      molecular phylogenetic analyses. Applying strain T6 to sterile soil could
      increase soil levels of Fe(2+) and siderophores, as well as increase Fe(2+) and
      Fe(3+)-chelate reductase (FCR) activity in cucumber tissues. Purified siderophore
      eluent (PSE) increased plant growth, thus confirming its role in plant growth
      promotion. Moreover, extracellular Fe(3+) reducing activity and three kinds of
      organic acids were detected in the culture filtrate of strain T6. These results
      indicate that strain T6 influences plant Fe absorption in several ways.
      Siderophore-based Fe chelation is effective in providing Fe to plants, organic
      acids, and Fe(3+) reducing enzymes may participate in the solubilization and
      reduction of insoluble Fe(3+) to Fe(2+).

PMID- 24861575
TI  - Quantitative T2 changes and susceptibility-weighted magnetic resonance imaging in
      murine pregnancy.
AB  - OBJECTIVE: To evaluate gestational age-dependent changes in the T2 relaxation
      time in normal murine placentas in vivo. The role of susceptibility-weighted
      imaging (SWI) in visualization of the murine fetal anatomy was also elucidated.
      METHODS: Timed-pregnant CD-1 mice at gestational day (GD) 12 and GD17 underwent
      magnetic resonance imaging. Multi-echo spin echo and SWI data were acquired. The
      placental T2 values on GD12 and GD17 were quantified. To account for the
      influence of systemic maternal physiological factors on placental perfusion,
      maternal muscle was used as a reference for T2 normalization. A linear mixed
      effects model was used to fit the normalized T2 values, and the significance of
      the coefficients was tested. Fetal SWI images were processed and reviewed for
      venous vasculature and skeletal structures. RESULTS: The average placental T2
      value decreased significantly on GD17 (40.17 +/- 4.10 ms) compared to the value
      on GD12 (55.78 +/- 8.13 ms). The difference in normalized T2 values also remained
      significant (p = 0.001). Using SWI, major fetal venous structures like the
      cardinal vein, the subcardinal vein, and the portal vein were visualized on GD12.
      In addition, fetal skeletal structures could also be discerned on GD17.
      CONCLUSION: The T2 value of a normal murine placenta decreases with advancing
      gestation. SWI provided clear visualization of the fetal venous vasculature and
      bony structures. (c) 2014 S. Karger AG, Basel.

PMID- 24861577
TI  - Breakthrough invasive fungal disease in patients receiving posaconazole primary
      prophylaxis: a 4-year study.
AB  - Posaconazole (PSC) is currently recommended as primary prophylaxis in neutropenic
      patients with acute myeloid leukaemia (AML) and in allogenic haematopoietic stem
      cell transplantation (AHSCT) recipients with graft-versus-host disease (GVHD).
      Studies focusing on breakthrough invasive fungal disease (IFD) upon PSC
      prophylaxis show disparate results. In order to evaluate the incidence of IFD in
      patients on PSC prophylaxis and identify IFD risk factors, we carried out a
      retrospective study of all consecutive patients on PP from January 2007 to
      December 2010 in our hospital. Breakthrough IFDs were identified from the
      database of the central pharmacy and the French administrative database (PMSI),
      registering final medical diagnoses of hospitalized patients. Medical data were
      reviewed to study proven or probable IFD, according to EORTC/MSG definition. PSC
      plasma concentrations (PPC) were also retrieved. Poisson models were used for
      statistical analysis. Two hundred and seventy-nine patients received PSC
      prophylaxis for a median duration of 1.4 months (range 0.2-17.9). Proven (n=6) or
      probable (n=3) IFDs were diagnosed in nine cases (3.2%). IFD incidence rate per
      100 person-month was 1.65 (95% CI, 0.79-2.97). IFDs were candidaemia (Candida
      glabrata, n=2), pulmonary invasive aspergillosis (n=3), disseminated fusariosis
      (n=2) and pulmonary mucormycosis (n=2). Seven deaths were reported, directly
      related to IFD in three patients (33.3%). First dosage of PPC under 0.3 mg/L was
      the single significant risk factor for IFD (RR, 7.77; 95% CI, 1.30-46.5; p
      0.025). Breakthrough IFD in patients receiving PSC prophylaxis is rare but
      associated with a poor outcome. Low PSC plasma concentrations are associated with
      an increased risk of IFD.

PMID- 24861578
TI  - Comparison of the effect of knee synovectomy in haemophilic patients with 153Sm-
      and 90Y-labelled hydroxyapatite 1 year after.
AB  - To compare the use of 740 Mbq (20 mCi) of (153) Sm and 185 Mbq (5mCi) of (90) Y,
      both labelling hydroxyapatite (HA), for knee synovectomy in haemophilic patients,
      1 year after the intervention. Thirty three men (36 knees) were studied, divided
      into two groups: 1 - treatment using 740 Mbq of (153) Sm-HA: 20 knees of 18
      patients, with mean age of 21.4 +/- 13.3 years (ranging from 7 to 56 years) and
      mean Pettersson score of 5.3; 2 - treatment using 185 Mbq of (90) Y-HA: 16 knees
      of 15 patients, with mean age of 26.3 +/- 10.3 (ranging from 7 to 51 years) and
      mean Pettersson score of 6.3. The following criteria were adopted for the
      evaluation before and 1 year after synovectomy: reduction in haemarthrosis
      episodes and pain using a visual analogue scale, as well as improved joint
      mobility. The occurrence of adverse events in the treatment was also considered.
      The chi-square, Wilcoxon and Mann-Whitney tests were used with P <= 0.05 set as
      significant. The occurrence of haemarthrosis declined by 65.7% with the use of
      (153) Sm-HA and 82.6% for (90) Y-HA, with no statistical difference between the
      groups (P = 0.632); pain reduction was 42.5% in group 1 and 30.7% in group 2,
      once again with no statistical difference (P = 0.637). Improvement in joint
      mobility was not significant for both groups. Two cases of mild reactive
      synovitis were observed in group 1 and one in group 2, which cleared up without
      medical intervention. Although the beta energy from (90) Y is the gold standard
      for knee synovectomy, higher activities of (153) Sm may be used in places which
      have only production of this material. 

PMID- 24861579
TI  - Spontaneous growth and division in self-reproducing inorganic colloidosomes.
AB  - Self-reproduction in compartmentalized chemical ensembles is a central issue for
      the development of new materials and processes capable of autonomous behavior,
      self-amplification and artificial evolution. Current approaches to synthetic
      cellularity focus primarily on self-assembled soft matter systems such as
      membrane-bounded lipid vesicles, which have sufficient structural plasticity to
      undergo growth and division. Steps towards inorganic protocells are being
      advanced, but self-reproduction in these more structurally robust micro
      compartments has not been demonstrated. Here, a primitive form of growth and
      division involving inorganic colloidosomes (Pickering emulsions), comprising
      aqueous micro-droplets enclosed by an ultrathin membrane of silica nanoparticles,
      is shown. Growth of the colloidosomes is induced by organosilane-mediated
      methanol formation, and results in a localized rupture of the inorganic membrane
      followed by outgrowth and separation of a second-generation protocell, which is
      stabilized by de novo nanoparticle assembly. These observations provide a first
      step towards synthetic cell-like inorganic materials capable of chemically
      induced self-reproduction. 

PMID- 24861581
TI  - Inflammatory and neuropathic pain are rapidly suppressed by peripheral block of
      hyperpolarisation-activated cyclic nucleotide-gated ion channels.
AB  - Previous studies have shown that hyperpolarisation-activated cyclic nucleotide
      gated (HCN)-2 ion channels regulate the firing frequency of nociceptive sensory
      neurons and thus play a central role in both inflammatory and neuropathic pain
      conditions. Here we use ivabradine, a clinically approved anti-anginal agent that
      blocks all HCN channel isoforms approximately equally, to investigate the effect
      on inflammatory and neuropathic pain of HCN ion channel block. We show that
      ivabradine does not have major off-target effects on a sample group of Na, Ca,
      and K ion channels, and that it is peripherally restricted because it is a
      substrate for the P-glycoprotein (PgP) multidrug transporter that is expressed in
      the blood-brain barrier. Its effects are therefore likely to be due to an action
      on HCN ion channels in peripheral sensory neurons. Using patch clamp
      electrophysiology, we found that ivabradine was a use-dependent blocker of native
      HCN channels expressed in small sensory neurons. Ivabradine suppressed the action
      potential firing that is induced in nociceptive neurons by elevation of
      intracellular cAMP. In the formalin model of inflammatory pain, ivabradine
      reduced pain behaviour only in the second (inflammatory) phase. In nerve injury
      and chemotherapy models of neuropathic pain, we observed rapid and effective
      analgesia as effective as that with gabapentin. We conclude that both
      inflammatory and neuropathic pain are rapidly inhibited by blocking HCN-dependent
      repetitive firing in peripheral nociceptive neurons. 

PMID- 24861580
TI  - Activation of mesocorticolimbic reward circuits for assessment of relief of
      ongoing pain: a potential biomarker of efficacy.
AB  - Preclinical assessment of pain has increasingly explored operant methods that may
      allow behavioral assessment of ongoing pain. In animals with incisional injury,
      peripheral nerve block produces conditioned place preference (CPP) and activates
      the mesolimbic dopaminergic reward pathway. We hypothesized that activation of
      this circuit could serve as a neurochemical output measure of relief of ongoing
      pain. Medications commonly used clinically, including gabapentin and nonsteroidal
      anti-inflammatory drugs (NSAIDs), were evaluated in models of post-surgical (1
      day after incision) or neuropathic (14 days after spinal nerve ligation [SNL])
      pain to determine whether the clinical efficacy profile of these drugs in these
      pain conditions was reflected by extracellular dopamine (DA) release in the
      nucleus accumbens (NAc) shell. Microdialysis was performed in awake rats. Basal
      DA levels were not significantly different between experimental groups, and no
      significant treatment effects were seen in sham-operated animals. Consistent with
      clinical observation, spinal clonidine produced CPP and produced a dose-related
      increase in net NAc DA release in SNL rats. Gabapentin, commonly used to treat
      neuropathic pain, produced increased NAc DA in rats with SNL but not in animals
      with incisional, injury. In contrast, ketorolac or naproxen produced increased
      NAc DA in animals with incisional but not neuropathic pain. Increased
      extracellular NAc DA release was consistent with CPP and was observed selectively
      with treatments commonly used clinically for post-surgical or neuropathic pain.
      Evaluation of NAc DA efflux in animal pain models may represent an objective
      neurochemical assay that may serve as a biomarker of efficacy for novel pain
      relieving mechanisms. 

PMID- 24861583
TI  - Association of acetazolamide infusion with headache and cranial artery dilation
      in healthy volunteers.
AB  - The carbonic anhydrase inhibitor acetazolamide causes extracellular acidosis and
      dilatation of cerebral arterioles. In this study, we tested the hypothesis that
      acetazolamide also may induce headache and dilatation of cranial arteries. In a
      randomized double-blind crossover study design, 12 young healthy women were
      allocated to injection of 1 g acetazolamide or placebo on 2 separate days. We
      recorded headache on a verbal rating scale from 0 to 10 during an immediate phase
      (0-90 minutes) and a delayed phase (2-12 hours). The circumference of cranial
      arteries was measured using 3T high-resolution magnetic resonance angiography 30
      and 60 minutes after injection. Acetazolamide provoked immediate headache in 9
      participants compared to 3 participants after placebo (P=.031). Eleven
      participants reported headache in the delayed phase after acetazolamide, compared
      with 4 after placebo (P=.016). The area under the curve for headache was
      increased after acetazolamide compared to placebo in the delayed phase (2-12 h)
      (P=.005). Compared to placebo, arterial circumference increased after
      acetazolamide in the basilar artery (P=.002) as well as the cerebral (P=.003),
      cavernous (P=.002), and cervical (P=.005) parts of the internal carotid artery,
      but no other extracranial arteries changed after acetazolamide. In conclusion,
      acetazolamide caused immediate and delayed headache as well as dilatation of
      intracranial arteries in healthy volunteers. It is possible that extracellular
      acidosis induced by acetazolamide causes sensitization of cephalic perivascular
      nociceptors, which, in combination with vasodilatation, leads to delayed
      headache.

PMID- 24861582
TI  - The responsive amygdala: treatment-induced alterations in functional connectivity
      in pediatric complex regional pain syndrome.
AB  - The amygdala is a key brain region with efferent and afferent neural connections
      that involve complex behaviors such as pain, reward, fear, and anxiety. This
      study evaluated resting state functional connectivity of the amygdala with
      cortical and subcortical regions in a group of chronic pain patients (pediatric
      complex regional pain syndrome) with age-sex matched control subjects before and
      after intensive physical-biobehavioral pain treatment. Our main findings include
      (1) enhanced functional connectivity from the amygdala to multiple cortical,
      subcortical, and cerebellar regions in patients compared with control subjects,
      with differences predominantly in the left amygdala in the pretreated condition
      (disease state); (2) dampened hyperconnectivity from the left amygdala to the
      motor cortex, parietal lobe, and cingulate cortex after intensive pain
      rehabilitation treatment within patients with nominal differences observed among
      healthy control subjects from time 1 to time 2 (treatment effects); (3)
      functional connectivity to several regions key to fear circuitry (prefrontal
      cortex, bilateral middle temporal lobe, bilateral cingulate, hippocampus)
      correlated with higher pain-related fear scores; and (4) decreases in pain
      related fear associated with decreased connectivity between the amygdala and the
      motor and somatosensory cortex, cingulate, and frontal areas. Our data suggest
      that there are rapid changes in amygdala connectivity after an aggressive
      treatment program in children with chronic pain and intrinsic amygdala functional
      connectivity activity serving as a potential indicator of treatment response. 

PMID- 24861584
TI  - Altered structure and function in hippocampus and medial frontal cortex in
      patients with burning mouth syndrome.

PMID- 24861585
TI  - Dose or content? Effectiveness of pain rehabilitation programs for patients with
      chronic low back pain: A systematic review. Aurthor reply.

PMID- 24861587
TI  - A change vector analysis technique for monitoring land cover changes in Copsa
      Mica, Romania, in the period 1985-2011.
AB  - During the communist regime, Romania's planned economy focused exclusively on
      production neglecting the environment protection. The lack of less polluting
      production technologies and of environmental protection measures led to excessive
      pollution in certain industrialized areas. This is the case of the town of Copsa
      Mica in Sibiu County, which in 1987 was considered one of the most polluted towns
      in Europe. The present study assesses the change vector analysis (CVA) technique
      using a Landsat Thematic Mapper (TM) image time series to monitor land cover
      changes caused by carbon black and heavy metal pollution. CVA was applied to the
      tasseled cap greenness (TCG) and tasseled cap brightness (TCB) indices, as well
      as to the Normalized Difference Vegetation Index (NDVI) and bare soil index (BI).
      Various maps were generated for the periods 1985-1994, 1994-2003, 2003-2011, and
      1985-2011, and threshold values were determined for the detection of land cover
      change/no change. The change direction and magnitude values were cross-tabulated
      and classified. The technique was assessed based on the change versus no-change
      error matrix. The results show that in the area of Copsa Mica, land cover changes
      occurred because of a considerable decrease in the area affected by carbon black
      and heavy metal pollution. The CVA technique proved efficient in monitoring the
      land cover changes caused by pollution and especially by carbon black pollution.
      Soil pollution by heavy metals is reflected in the bare soil surfaces present in
      the imagery. 

PMID- 24861586
TI  - Prospective double-blind preoperative pain clinic screening before microsurgical
      denervation of the spermatic cord in patients with testicular pain syndrome.
AB  - Testicular pain syndrome (TPS), defined as an intermittent or constant pain in
      one or both testicles for at least 3 months, resulting in significant reduction
      of daily activities, is common. Microsurgical denervation of the spermatic cord
      (MDSC) has been suggested as an effective treatment option. The study population
      comprised 180 TPS patients admitted to our outpatient urology clinic between 1999
      and 2011. On 3 different occasions, patients were offered a double-blind, placebo
      controlled temporary blockade of the spermatic cord. A single blockade consisted
      of 10 mL 2% lidocaine, 10 mL 0.25% bupivacaine, or 10 mL 0.9% sodium chloride. If
      the results of these blockades were positive, MDSC was offered. All MDSCs were
      performed by a single urologist (M.T.W.T.L.) using an inguinal approach. Pain
      reduction was determined at prospective follow-up. This study evaluated 180
      patients. Most patients (61.1%) had undergone a scrotal or inguinal procedure.
      Patients had complaints during sexual activities (51.7%), sitting (37.5%), and/or
      cycling (36.7%); 189 randomized blockades were offered to all patients. There was
      a positive response in 37% and a negative response in 51%. MDSC was performed on
      58 testicular units, including 3 patients with a negative outcome of the
      blockades. At mean follow-up of 42.8 months, 86.2% had a >= 50% reduction of pain
      and 51.7% were completely pain free. MDSC is a valuable treatment option for TPS
      patients because in this study 86.2% experienced a >= 50% reduction of pain. To
      prevent superfluous diagnostics and treatment, it is mandatory to follow a
      systematic protocol in the treatment of TPS.

PMID- 24861588
TI  - An assessment of metal contamination risk in sediments of Hara Biosphere Reserve,
      southern Iran with a focus on application of pollution indicators.
AB  - The aim of this study was to assess the pollution status of metals in sediments
      of Hara Biosphere Reserve using pollution indicators. For this purpose, sediment
      samples from nine locations were collected and characterized for metal content
      (Pb, Cr, Zn, Cu, and Fe) using the total digestion technique. Comparison of metal
      concentrations with that of sediment quality guidelines (SQGs) demonstrated no
      association with negative biological effects for Cu and Zn, while the values of
      Pb and Cr mainly illustrated to have association with negative biological
      effects. The results of the geo-accumulation index (Igeo) indicated no
      contamination for Cr, Cu, Zn, and Fe, while the values of Pb demonstrated to have
      moderate contamination based on I geo values. The analysis of the enrichment
      factor (EF) showed no enrichment for Cu and Zn and minor enrichment for Pb and
      Cr. Similar results were also found for quantification of contamination (QoC)
      analysis, where the values of Cu and Zn demonstrated to have a geogenic source of
      contamination, while the values of Pb and Cr mainly illustrated to have an
      anthropogenic source of contamination. According to EF and QoC calculations, the
      values of Cu and Zn were derived mainly from natural processes and exposure of
      material from the earth's crust, while the values for Pb and Cr were enriched by
      anthropogenic activities. The results of the contamination factor (Cf(i))
      demonstrated low contamination levels for Fe, Cr, Zn, and Cu and moderate
      contamination levels for Pb. The pollution load index (PLI), showing the overall
      contamination of metals, demonstrated moderate pollution status in the study
      area.

PMID- 24861589
TI  - Coexpression networks predict ataxia genes.

PMID- 24861590
TI  - A modified procedure for gas-source isotope ratio mass spectrometry: the long
      integration dual-inlet (LIDI) methodology and implications for clumped isotope
      measurements.
AB  - RATIONALE: High-precision stable isotope measurements in gas-source isotope ratio
      mass spectrometry are generally carried out by repeated comparison of the
      composition of an unknown sample with that of a working gas (WG) through a dual
      inlet (DI). Due to the established DI protocols, however, most of the sample gas
      is wasted rather than measured, which is a major problem when sample size is
      limited. Here we propose a new methodology allowing the measurement of a much
      larger portion of the available sample. METHODS: We tested a new measurement
      protocol, the long-integration dual-inlet (LIDI) method, which consists of a
      single measurement of the sample for 200 to 600 seconds followed by a single
      measurement of the WG. The isotope ratios of the sample are calculated by
      comparison of the beam ratios of the WG and sample at equivalent intensities of
      the major ion beam. RESULTS: Three isotopically very different CO2 samples were
      analyzed. The LIDI measurements of large samples (50 to 100 umol of CO2) measured
      at quasi-constant beam sizes, and of small samples (1.5 to 2 umol of CO2)
      measured in micro-volume mode, generated results that are indistinguishable from
      the standard DI measurements for carbon, oxygen and clumped isotope compositions.
      The external precision of Delta47 using the LIDI protocol (~+/-0.0070/00) is
      similar to that of the state of the art DI measurements. CONCLUSIONS: For
      traditional and clumped isotope measurements of CO2, the LIDI protocol allows the
      measurement of a much larger portion of the sample gas rather than only ~20% of
      it. In addition, the sample can be measured at higher signal intensity and for
      longer time, allowing the measurement of smaller samples while preserving
      precision. We suggest that other gases commonly used for stable isotope
      measurements with gas-source mass spectrometry would also benefit from this new
      protocol.

PMID- 24861591
TI  - Quantification of intact human insulin-like growth factor-I in serum by nano
      ultrahigh-performance liquid chromatography/tandem mass spectrometry.
AB  - RATIONALE: Insulin-like growth factor-I is one of the biomarkers used to detect
      growth hormone administration prohibited in human sport. Current testing
      approaches for IGF-I rely on commercial immunoassays, which may change from time
      to time requiring complex revalidation. Mass spectrometry (MS)-based approaches
      often rely on enzymatically digesting the protein and measuring specific peptide
      concentrations. In order to reinforce the current available methodology for IGF-I
      testing, a reliable and equally sensitive MS method is required for the analysis
      of intact protein using small sample volumes (<25 MUL). METHODS: IGF-I was
      extracted from human serum samples by a simple protein precipitation procedure.
      Separation was achieved via nano-ultrahigh-performance liquid chromatography and
      MS analysis was conducted by nano-electrospray ionisation triple-quadrupole mass
      spectrometry in the selected reaction monitoring mode using a stable-isotope
      labelled internal standard. RESULTS: A six-point calibration curve ranging from
      50 to 1000 ng/mL of human IGF-I in rat serum was used to establish instrument
      response. The method provided a limit of quantification of 50 ng/mL, with intra-
      and inter-day precision <=5% and intra- and inter-day accuracy >=95%.
      CONCLUSIONS: A quantitative method was developed for the quantification of intact
      IGF-I in human serum samples. The data generated provided important information
      for the development of a new reference method for the growth hormone biomarker
      test and helped create a reliable system for monitoring peptide hormones in
      individual athletes, a possible extension to the athlete biological passport
      system. Nano-electrospray has here been shown to be sufficiently robust for
      routine use in an analytical laboratory, allowing for the analysis of minute
      sample volumes.

PMID- 24861592
TI  - A revisit of high collision energy effects on collision-induced dissociation
      spectra using matrix-assisted laser desorption/ionization tandem time-of-flight
      mass spectrometry (MALDI-LIFT-TOF/TOF): application to the sequencing of RNA/DNA
      chimeras.
AB  - RATIONALE: High-energy collision-induced dissociation (CID) spectra of isomeric
      RNA/DNA chimeras using matrix-assisted laser desorption/ionization time-of-flight
      LIFT mass spectrometry (MALDI-LIFT-TOF/TOF) can potentially be applied for an
      exhaustive fragment characterization in a nucleic acid sequencing scheme. These
      chimeras contain deoxynucleotides and at the 3'-end a ribonucleotide with a 3'
      phosphate group. METHODS: Deprotonated RNA/DNA chimeras of 4-, 5-, 7- and 10-mers
      are analyzed by CID. This enhances consecutive dissociations from both the
      precursor and prompt product anions generated by MALDI and metastable
      fragmentations prior to entering the LIFT cell. RESULTS: Gas-phase fragmentations
      of 4- and 5-mers produced many fragment ions, from base release prior to
      consecutive cleavage of the nucleotide phosphate bond linkage phosphate. The
      unusual a4(-) product ion is a specific and diagnostic dissociation of the 4-mer
      if the ribonucleotide contains cytosine. As the size of RNA/DNA chimeras
      increase, several abundant product ions are generated mainly from zwitterionic
      forms (deprotonated phosphate ester and protonated base sites): [(M-H)-BiH](-),
      [ai-BiH](-), wj(-), [wj, (ai-BiH)](-) (if Bi  ? T) as internal product ion, and
      more rarely [wj-BiH](-). The absence of the majority of the [ai-BiH](-) series
      although the wj (-) series suggested that the higher critical energy processes
      with a loose transition state are favored yielding the wj(-) series. A large
      number of abundant fragment ions are detected which enable each isomer to be
      sequenced. CONCLUSIONS: This sequencing method is high-throughput, accurate and
      could be used to sequence isomers of up to 10-mers and also oligonucleotides of
      unknown sequence. However, RNA/DNA chimeras without thymine must be sufficiently
      concentrated to reach desorption of deprotonated molecular species to be selected
      in LIFT to produce all fragment ions within measurable abundances.

PMID- 24861593
TI  - Continuous and unattended measurements of the site preference of nitrous oxide
      emitted from an agricultural soil using quantum cascade laser spectrometry with
      intercomparison with isotope ratio mass spectrometry.
AB  - RATIONALE: The difference between the (15)N natural abundance of (14)N-(15)N-O
      and (15)N-(14)N-O (site preference; SP) is used to understand the mechanisms
      underlying N2O emissions from soils. We investigated the use of quantum cascade
      laser (QCL) absorption spectrometry for continuous and precise analysis of the SP
      of N2O emitted from a field soil at atmospheric mixing ratios. METHODS: A QCL
      based spectrometer was used to determine the SP of soil-emitted N2O accumulated
      in a closed chamber system without preconcentration. N2O standards (<2500 ppbv)
      were used to evaluate the precision of the QCL spectrometry (QCLS) system. CO2
      and H2O were removed from the gas samples. Intercomparison measurements of QCLS
      and isotope ratio mass spectrometry (IRMS) were performed on N2O calibration
      gases at different mixing ratios. The observed dependency of the QCLS result on
      the N2O mixing ratio was corrected. RESULTS: Measurement of SP of N2O emitted
      from the field suggested that the SP of N2O varied from 0 to 400/00 over a period
      of 1 month. The precisions of the SP measurements (300-2500 ppbv) were <1.90/00
      for delta(15)N(alpha) values, <2.60/00 for delta(15)N(beta) values, <2.10/00 for
      delta(15)N(bulk) values, and <2.10/00 for the SP (1 min averaging time) obtained
      on a once-an-hour calibrated QCLS system, with a cell temperature control
      precision of +/-0.01 K. CONCLUSIONS: Continuous and unattended measurements of
      the SP of N2O emitted from soils were achieved at low N2O mixing ratios. The
      accuracy of the QCLS measurements for the SP of N2O was significantly improved by
      precisely controlling the temperature of the system and by correcting for the
      concentration dependency of the raw data through an intercomparison with IRMS
      measurements.

PMID- 24861594
TI  - Enhanced specificity for phosphatidylcholine analysis by positive ion mode matrix
      assisted laser desorption/ionization imaging mass spectrometry.
AB  - RATIONALE: Visualization of the spatial distribution of phosphatidylcholine (PC)
      in tissues by matrix-assisted laser desorption/ionization imaging mass
      spectrometry (MALDI-IMS) provides insights into key physiological and
      pathophysiological processes. In MALDI-IMS analysis, the heterogeneity of adduct
      ions formed from PC lowers the specificity of detection of PC molecular species
      and poses a challenge in the identification of these species. To solve this
      problem, modified matrix solution and desalting with ammonium acetate (NH4 Ac)
      buffer have been employed. However, the utility of these methods is limited to
      the analysis of brain sections. METHODS: The MALDI signal intensities of [PC+H],
      [PC+Na] and [PC+K] were compared after three different pretreatments (modified
      matrix solution, desalting with 150 mM ammonium acetate, treatment with 150 mM
      potassium acetate). RESULTS: Pretreatment of tissue sections with 150 mM
      potassium acetate resulted in an increase in the signal intensity of [PC+K] ions
      produced from cryosections of the pancreas, brain, and liver tissues.
      CONCLUSIONS: Pretreatment with potassium acetate can be a simple, improved, and
      highly useful method for the reliable analysis of PC in tissues.

PMID- 24861595
TI  - Metabolic pathway monitoring of phenalinolactone biosynthesis from Streptomyces
      sp. Tu6071 by liquid chromatography/mass spectrometry coupling.
AB  - RATIONALE: A rapid and precise analytical method for the investigation of natural
      products is required for pathway monitoring of the biosynthesis of secondary
      metabolites. Phenalinolactones, used in antibiotic research, are produced by
      Streptomyces sp. Tu6071. For the analysis of those compounds, prior to mass
      spectrometric analysis, an efficient separation technique is required. METHODS:
      For the identification of phenalinolactones from liquid cultures of Streptomyces
      sp. Tu6071, a new method comprising the combination of solid-phase extraction
      (SPE) prior to liquid chromatography/electrospray ionization tandem mass
      spectrometry (LC/ESI-MS/MS) was established. MS/MS product ion scans were applied
      for phenalinolactone detection and structure elucidation, performed in negative
      mode and optimized for sensitivity and specificity. For the discovery of new
      intermediates, a MS/MS precursor ion scan was applied. RESULTS: Analysis of the
      extracts revealed that the Oasis(r) MAX cartridge, containing a quaternary amine
      functionality, is the most efficient SPE material for purification of
      phenalinolactones, since it allowed sufficient enrichment and detection of
      intermediates from the biosynthetic pathway by LC/ESI-MS/MS. Using the precursor
      ion scan technique, two new secondary metabolites, PL IM1 with m/z 672.6 and PL
      IM2 with m/z 433.3, have been detected. The structures of the new intermediates
      are postulated and arranged into the biosynthetic pathway of phenalinolactones.
      CONCLUSIONS: A precise analytical method was established for the identification
      of phenalinolactones by combining purification from Streptomyces using SPE prior
      to LC/ESI-MS/MS. By optimising LC/ESI-MS/MS settings, this method has been
      successfully applied for pathway monitoring of secondary metabolites. Application
      of a precursor ion scan allowed for the identification of unknown intermediates
      in biosynthetic pathways.

PMID- 24861596
TI  - Novel method to analysis benzo[a]pyrene in filter by liquid chromatography/tandem
      mass spectrometry: application to assess mouth level benzo[a]pyrene exposure.
AB  - RATIONALE: Benzo[a]pyrene (B[a]P) is a well-known carcinogenic compound produced
      from incomplete combustion of organic compounds. During cigarette smoking,
      cigarette filters trap a portion of mainstream smoke B[a]P and accurate
      measurement of B[a]P levels in cigarette filter can be used to estimate human
      exposure level of this compound. METHODS: A rapid and sensitive method to
      quantify B[a]P levels trapped by cigarette filter was developed. The method is
      based on liquid chromatography/atmospheric pressure photoionization tandem mass
      spectrometry (LC/APPI-MS/MS). Validation was provided in smoked cigarette filter.
      RESULTS: The method involved no extensive manual cleanup and concentration steps,
      hence is easy to use. The limit of detection was 0.064 ng/mL. The recovery ranged
      from 82.68% to 103.27% and the relative standard deviation (RSD) was less than
      7%. A regression model between mainstream cigarette smoke and trapped B[a]P by
      cigarette filter was established (y = 2.5089x - 0.1851, R(2) = 0.999, n = 6).
      This model was applied to estimate mouth-level B[a]P exposure of smokers.
      CONCLUSIONS: The LC/APPI-MS/MS method developed in this work had an excellent
      throughput in estimating the mouth-level exposure under natural human smoking
      conditions. Mouth-level B[a]P exposure based on a study of three cigarettes (8,
      10 and 13 mg tar levels) showed significant positive correlations with B[a]P
      trapped by cigarette filter measured (y = 2.5456x - 0.5056, R(2) = 1, n = 249).

PMID- 24861598
TI  - Simultaneous determination of biotoxins DSP and AZAs in bivalve molluscs and fish
      by liquid chromatography/tandem mass spectrometry.
AB  - RATIONALE: A method has been developed for simultaneous determination of the
      toxins OA, DTX-1, AZA-1, AZA-2 and AZA-3 in various aquatic products as these can
      cause diarrhoetic shellfish poisoning (DSP) in humans, an intoxication
      characterized by vomiting and diarrhea. METHODS: Separation of the toxins was
      achieved on a C18 column (150 mm * 2.1 mm, 3.5 um) using an acetonitrile/water
      gradient with formic acid as an eluent modifier. Electrospray ionisation (ESI) in
      negative mode was used to generate the molecule related ion [M-H](-), for OA and
      DTX-1, while ESI in positive mode was used to generate the molecule related ion
      [M+H](+) for AZAs. Samples were extracted with 80% methanol, followed by
      partitioning with ethyl acetate, purified on a Poly-Sery MAX cartridge and
      finally analyzed by LC/ESI-MS/MS in the multiple reaction monitoring (MRM) mode.
      RESULTS: The limit of detection (LOD) and limit of qualification (LOQ) of the
      method were in the range of 0.02-0.79 ug/kg and 0.07-2.64 ug/kg in Scomberomorus
      niphonius, blood clam and oyster, respectively, recoveries of the toxins at three
      fortification levels ranged from 71.3% to 104.8% with relative standard deviation
      from 1.0% to 12.5%. The calibration curves were well linear between the LC peak
      area of the selected ion pair and the concentration of the toxins, with the
      correlation coefficient over 0.99. CONCLUSIONS: The method was sufficiently
      sensitive to permit the determination of the toxins DSP and AZA in sea food.

PMID- 24861597
TI  - Determination of ten hexabromocyclododecane diastereoisomers using two coupled
      reversed-phase columns and liquid chromatography/tandem mass spectrometry.
AB  - RATIONALE: Hexabromocyclododecanes (HBCDs) are raising concern due to their
      potential persistence, bioaccumulation and toxicity. Apart from the widely
      reported isomers alpha-, beta-, gamma-HBCD, other HBCD diastereoisomers such as
      delta-HBCD have been also recently found in environmental media and biota. These
      newly reported diastereoisomers might give more insight into the degradation and
      biotransformation of HBCDs. METHODS: A reversed-phase C18 column coupled to a C8
      column was used to improve the chromatographic resolution. A gradient mobile
      phase consisting of methanol, acetonitrile, and water, as well as tandem mass
      spectrometry parameters, were optimized. Ten HBCD diastereoisomers were finally
      determined by liquid chromatography/tandem mass spectrometry in multiple reaction
      monitoring mode with negative electrospray ionization. RESULTS: Eight of the ten
      HBCDs could be chromatographically separated by using the coupled reversed-phase
      columns. Results of the method validation indicate high reproducibility and good
      sensitivity. The limit of detection ranged from 0.4 to 0.8 pg, and the relative
      standard deviations of intra- and inter-day injections ranged from 1.8 to 5.1%
      and from 2.7 to 9.5%, respectively. The developed method was further applied to
      the analysis of HBCDs in HBCD commercial products and soil samples. delta-, eta-,
      theta-, and epsilon-HBCD were detected in commercial products and soil samples.
      CONCLUSIONS: The present study revealed that delta-, eta-, theta-, and epsilon
      HBCD might occur ubiquitously in environmental media and biota. These newly
      reported diastereoisomers may help us to better understand the fate and
      transformation of HBCDs in the environment.

PMID- 24861599
TI  - Guanidinated protein internal standard for immunoaffinity-liquid
      chromatography/tandem mass spectrometry quantitation of protein therapeutics.
AB  - RATIONALE: A protein internal standard (IS) is essential and superior to a
      peptide IS to achieve reproducible results in the quantitation of protein
      therapeutics using immunoaffinity-liquid chromatography/tandem mass spectrometry
      (LC/MS/MS). Guanidination has been used as a protein post-modification technique
      for more than half a century. A decade ago, the modification was applied to
      lysine-ending peptides to enhance their MALDI responses and peptide sequencing
      coverage. However, rarely has tryptic digestion of guanidinated proteins been
      investigated, likely due to the early conclusion that trypsin did not hydrolyze
      peptide bonds involving homoarginine in guanidinated proteins. In this study, the
      opposite was observed. Guanidinated lysine residues of proteins did not hinder
      the access of trypsin allowing for proteolytic digestion. Based on this
      observation, a new concept of internal standard, named Guanidinated Protein
      Internal Standard (GP-IS), was proposed for LC/MS/MS quantitation of protein
      therapeutics. METHODS: The GP-IS is prepared by treating a portion of the
      therapeutic protein (analyte) with guanidine to convert arginine residues in the
      protein into homoarginine residues. After tryptic digestion, the GP-IS produces a
      series of homoarginine-ending peptides plus another series of arginine-ending
      peptides. One of the homoarginine-ending peptides, which corresponds to the
      analyte surrogate (lysine-ending) peptide, was chosen as a peptide internal
      standard (GP-PIS) for LC/MS/MS quantitation. RESULTS: Using this GP-IS approach,
      a sensitive and robust immunoaffinity-LC/MS/MS assay was developed and fully
      validated with a linearity range from 10 to 1000 ng/mL using 200 MUL of human
      serum for the quantitation of an Astellas protein drug in clinical development.
      CONCLUSIONS: The proposed strategy allows LC/MS/MS to play an ever-increasing
      role in bioanalytical support for protein therapeutics development because of its
      capability of completely tracking all variations from the beginning to the end of
      sample analysis, easier preparation compared to isotope-labeled protein-IS, and
      greater flexibility for changing to alternate analyte surrogate peptides.

PMID- 24861600
TI  - Measuring xenon in human plasma and blood by gas chromatography/mass
      spectrometry.
AB  - RATIONALE: Due to the favorable pharmacokinetic properties and minimal side
      effects of xenon, its use in modern anesthesia has been well accepted, and recent
      studies further demonstrated the intra- and postoperative neuro-, cardio-, and
      reno-protective action of the noble gas. Since the production of the hypoxia
      inducible factor 1alpha (HIF-1alpha) and its downstream effector erythropoietin
      as well as noradrenalin reuptake inhibition have been found to play key roles in
      this context, the question arose as to whether the use of xenon is a matter for
      doping controls and preventive doping research. The aim of the present study was
      hence to evaluate whether the (ab)use of xenon can be detected from doping
      control samples with the instrumentation commonly available in sports drug
      testing laboratories. METHODS: Plasma was saturated with xenon according to
      reported protocols, and the target analyte was measured by means of gas
      chromatography/time-of-flight and triple quadrupole mass spectrometry with
      headspace injection. Recording the accurate mass of three major xenon isotopes at
      m/z 128.9048, 130.9045 and 131.9042 allowed for the unequivocal identification of
      the analyte and the detection assay was characterized concerning limit of
      detection (LOD), intraday precision, and specificity as well as analyte recovery
      under different storage conditions. RESULTS: Xenon was detected in fortified
      plasma samples with detection limits of approximately 0.5 nmol/mL to 50 nmol/mL,
      depending on the type of mass spectrometer used. The method characteristics of
      intraday precision (coefficient of variation <20%) and specificity demonstrated
      the fitness-for-purpose of the analytical approach to unambiguously detect xenon
      at non-physiological concentrations in human plasma and blood. Eventually,
      authentic plasma and blood samples collected pre-, intra-, and post-operative (4,
      8, and 24 h) were positively analyzed after storage for up to 30 h, and provided
      proof-of-concept for the developed assay. CONCLUSIONS: If relevant to doping
      controls, xenon can be determined from plasma and blood samples, i.e. common
      specimens of routine sports drug testing in the context of Athlete Biological
      Passport (ABP) analyses. Optimization of sampling and analytical procedures will
      allow the detection limit to be further improved and potentially enable accurate
      quantification of the anesthetic agent.

PMID- 24861601
TI  - Comprehensive gas chromatography-electron ionisation mass spectrometric analysis
      of fatty acids and sterols using sequential one-pot silylation: quantification
      and isotopologue analysis.
AB  - RATIONALE: Fatty acids and sterol lipids play crucial roles in several biological
      processes and several biological facts underline the interconnection between
      these lipid classes. Therefore, it is of interest to develop a comprehensive
      method analysing both classes in the form of their most favourable derivatives
      suitable for quantification and isotopologue analysis. METHODS: Lipids were
      derivatised by a sequential one-pot procedure using N-tert-butyldimethylsilyl-N
      methyltrifluoroacetamide (MtBSTFA) and N,O-bis(trimethylsilyl)trifluoroacetamide
      (BSTFA). No clean-up or concentration steps were necessary. The prepared samples
      were directly available for gas chromatography-electron ionisation mass
      spectrometric (GC-EI-MS) analysis on a standard column. For quantification, the
      SIM mode was used and for isotopologue analysis scheduled scan mode was applied.
      RESULTS: Development of a sequential one-pot derivatisation for GC-EI-MS allowing
      comprehensive analysis of fatty acids and sterols as their most favourable
      derivatives. Validation carried out using human plasma, comparison with certified
      NIST plasma. LLOQ of usually 3.3 ng/mL achieved. Isotopologue analysis of 2
      [(13)C]-acetate incorporation in HL-60 cells proving feasibility of method.
      CONCLUSIONS: The presented method successfully combines two consecutive
      silylation reactions in one pot, enabling the analysis of both fatty acids and
      sterols in a comprehensive analytical method. The method has great potential for
      the quantification of lipids as well as the comprehensive study of both
      biochemical pathways, using [(13)C]-flux analysis.

PMID- 24861602
TI  - Distribution of lysophosphatidylcholine in the endosperm of Oryza sativa rice.
AB  - RATIONALE: Sake is made from fermented rice and has been drunk in Japan for more
      than 1000 years. The rice must be polished prior to fermentation to obtain high
      quality sake. It is traditionally recognized that the quality of sake is improved
      as the rice polishing ratio (percentage removed in the polishing process)
      increases. However, the underlying chemistry of the rice polishing process is
      incompletely understood. Herein, we analyzed the distribution of
      lysophosphatidylcholine (LPC) molecular species with unsaturated fatty acids in
      rice, as their presence is thought to exert a negative effect on the flavor of
      sake. METHODS: The distribution of LPC molecular species in rice was visualized
      via matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI
      MSI). RESULTS: LPC (16:0) is ubiquitously present in the endosperm of rice while
      LPC (18:0) is localized in the core of the endosperm. In contrast, LPC (18:2) and
      LPC (18:1) are present in the outer region of the endosperm. CONCLUSIONS: The
      enhancement of the quality of sake as the polishing ratio of the rice increases
      might be explained in terms of the distribution of LPC with unsaturated fatty
      acids in the rice.

PMID- 24861603
TI  - Enhanced signal intensity in matrix-free laser desorption ionization mass
      spectrometry by chemical modification of bionanostructures from diatom cell
      walls.
AB  - RATIONALE: Laser desorption ionization for mass spectrometric measurements (LDI
      MS) is supported by nanostructured materials. This technique helps to overcome
      known limitations of matrix-assisted laser desorption/ionization (MALDI) and
      especially avoids interfering signals caused by matrix components. LDI can be
      supported by bionanostructures from the cell walls of diatoms. We explore how
      ionization efficiency can be improved by chemical modification of the cell walls.
      METHODS: We introduce procedures to chemically modify these nanopatterned
      silicate structures using perfluorooctyldimethylchlorosilane or
      pentafluorophenylpropyldimethylchlorosilane. Using a conventional MALDI-MS
      instrument we compare ionization using the novel materials with that of
      unmodified cell walls. The functionalized bionanomaterial is comprehensively
      evaluated for the use in LDI MS using a broad range of analytes and two
      commercial drugs. RESULTS: Chemical modifications lead to materials that support
      LDI significantly better than unmodified diatom cell walls. LDI signal intensity
      was up to 25-fold increased using the modified preparations. No interfering
      signals in the lower molecular weight range down to m/z 100 were observed,
      demonstrating the suitability of the method for small analytes. Crude solutions
      of commercial drugs, such as Aspirin complex((r)) and IbuHEXAL((r)) could be
      directly investigated without additional sample preparation. CONCLUSIONS:
      Chemically modified diatom cell walls represent a powerful tool to support
      ionization in LDI MS. The lack of background signals in the low molecular weight
      region of the mass spectra allows also the investigations of small analytes.

PMID- 24861604
TI  - Isolation and stable nitrogen isotope analysis of ammonium ions in ammonium
      nitrate prills using sodium tetraphenylborate.
AB  - RATIONALE: Because of the threat of bombings using improvised explosives
      containing ammonium nitrate (AN), law enforcement and intelligence communities
      have been interested in stable isotope techniques for tracking and discriminating
      AN sources. Separate analysis of the AN component ions ammonium and nitrate would
      add discriminatory power to these techniques. METHODS: Ammonium ions in dissolved
      AN solution were isolated from samples by precipitation using sodium
      tetraphenylborate solution. We tested the isolation of ammonium from nitrates
      using solutions of ammonium and nitrate salts with different (15)N/(14)N isotope
      ratios. Ammonium tetraphenylborate and AN were separately analyzed for their
      (15)N/(14)N isotope ratios using EA-ConFlo-IRMS, and the (15)N/(14)N isotope
      ratios of the nitrate ions were calculated using mass balance. Ammonium and
      nitrate nitrogen isotope ratios were plotted as two separate variables. RESULTS:
      Isolation of ammonium precipitate from solutions containing dissolved nitrates
      did not influence the nitrogen isotope ratios of test ammonium salts. A survey
      set of 42 AN samples showed that the ammonium and nitrate (15)N/(14)N isotope
      ratios were not significantly correlated, and the paired mean differences were
      not statistically significant. Both ammonium and nitrate were depleted in (15)N
      relative to their theoretical atmospheric sources. CONCLUSIONS: Isolation of the
      ammonium ion from AN adds another dimension for the discrimination of forensic AN
      samples. This technique using sodium tetraphenylborate is robust and does not
      require specialized equipment. Our observations indicated that ammonium nitrogen
      and nitrate nitrogen have independent sources of isotopic variation.

PMID- 24861605
TI  - Development of a highly sensitive liquid chromatography/tandem mass spectrometry
      method to quantify total and free levels of a target protein, interferon-gamma
      inducible protein-10, at picomolar levels in human serum.
AB  - RATIONALE: Liquid chromatography/tandem mass spectrometry (LC/MS/MS) assays are
      increasingly being used for absolute quantitation of proteins due to high
      specificity and low cost. However, the major challenge for the LC/MS method is
      insufficient sensitivity. This paper details the strategies developed to maximize
      the sensitivity from aspects of chromatography, mass spectrometry, and sample
      preparation to achieve a highly sensitive LC/MS method. METHODS: The method is
      based on the LC/MS/MS measurement of a surrogate peptide generated from trypsin
      digestion of interferon-gamma-inducible protein-10 (IP-10). The sample
      preparation strategy involved selectively extracting IP-10 and removing high
      abundance serum proteins through acidified protein precipitation (PPT). It was
      revealed in this work that these high-abundance serum proteins, if not separated
      from the protein of interest, could cause significant ionization saturation and
      high background noise in selected reaction monitoring (SRM), leading to a 100
      fold higher lower limit of quantification (LLOQ). RESULTS: Our method
      demonstrated that the acidified PPT could be optimized to selectively extract the
      protein of interest with full recovery of 97% to 103%, while the high-abundance
      serum proteins could be effectively removed with minimal matrix effect of 90% to
      93%. For the first time, a highly sensitive LC/MS method with a LLOQ of 31.62 pM
      for the quantitation of IP-10 has been achieved, which is a 100-fold improvement
      over the generic method. CONCLUSIONS: The described method offers excellent
      sensitivity with advantages of being antibody reagent independent and leads to
      significant cost and time savings. It has been successfully employed to determine
      both total and free IP-10 levels in human serum samples. This method development
      strategy may also be applied to other small proteins.

PMID- 24861606
TI  - Desorption electrospray ionization high-resolution mass spectrometry for the fast
      investigation of natural polysaccharide interactions with a model drug in
      controlled release systems.
AB  - RATIONALE: The control of drug release involves gaining an understanding of the
      complex interaction networks among drug-excipients-matrix-biological fluids.
      Thus, novel analytical methods that will lead to a better understanding of these
      interaction networks are urgently required. METHODS: Desorption electrospray
      ionization high-resolution mass spectrometry (DESI-HRMS) was used to evaluate the
      behaviour of four biocompatible polysaccharides (chondroitin sulfate, chitosan,
      sodium alginate and lambda-carrageenan) in the release of atenolol (ATN) from
      drug tablets. An aqueous solution at three different pH values (pH 7.4, 4.5 and
      1.2) was electrosprayed onto the tablets, allowing direct, fast, sensitive
      detection of atenolol as the protonated molecule in positive ion mode.
      Information about the desorption mechanism was obtained by analyzing the ATN
      [M+H](+) ion signal as a function of time. ATN-polymer interactions in the
      drug/polymer mixtures were also studied by Horizontal Attenuated Total
      Reflectance (HATR) Fourier transform infrared (FTIR) spectroscopy. RESULTS: The
      DESI-MS results revealed statistically different ATN desorption trends as a
      function of the polysaccharide investigated and the pH of the desorbing solution.
      Different release kinetics were ascribed to the drug-polymer interactions, and to
      the diffusion process of the drug through the hydrated polymer mesh. In
      particular, the alginate and lambda-carrageenan matrices were able to sustain
      drug release from the tablet even for a highly soluble drug. The HATR results
      confirmed the presence of ATN-polymer interactions that, depending on the polymer
      drug-solvent combination used, might affect ATN diffusion. CONCLUSIONS: These
      results suggest that DESI-MS has a potential role for the micro-environmental
      analysis of drug diffusion and surface distribution in polymeric matrices.

PMID- 24861607
TI  - Sampling reliability, spatial resolution, spatial precision, and extraction
      efficiency in droplet-based liquid microjunction surface sampling.
AB  - RATIONALE: Droplet-based liquid extraction approaches for spatially resolved
      surface sampling coupled with high-performance liquid chromatography/mass
      spectrometry (HPLC/MS) provide the ability to deal with complex sample matrices
      and to identify isomeric compounds not distinguishable by MS methods alone.
      Improvements in sampling reliability, spatial resolution, spatial precision and
      extraction efficiency are required to further the analytical utility of such
      sampling systems. METHODS: An autosampler capable of droplet-based liquid
      extraction was coupled with an HPLC/MS system. Visual inspection of the junction
      formation between the probe and a glass surface allowed evaluation of the liquid
      junction formation reliability, spatial location and size as a function of
      variable parameters such as solvent composition, probe-to-surface distance and
      droplet volume during solvent dispense and aspiration. Quantitative analysis of a
      component from a model surface using a weak extraction solvent was used to
      evaluate the effect of extraction time and number of extraction cycles on analyte
      extraction efficiency. RESULTS: Reliable junction formation, independent of other
      variable parameters, was realized simply by maintaining a maximum distance of 0.4
      mm between the probe and the sample surface. The smallest liquid junction
      diameter (1.6 mm) was observed when using a 1 MUL dispensed volume and 90%
      aqueous extraction solvent with either methanol or acetonitrile. Good sampling
      precision was always achieved using an extraction solvent with at least 50%
      methanol or acetonitrile by volume. Quantitative sampling of rhodamine B from a
      magenta Sharpie ink surface using a weak extraction solvent showed that
      extraction efficiency could be improved by increasing the extraction time or the
      number of extraction cycles. CONCLUSIONS: A platform employing a commercially
      available autosampler coupled to HPLC/MS was developed and successfully applied
      to investigate the effect of different sampling parameters on the reliability,
      spatial resolution, spatial precision and extraction efficiency of the liquid
      junction surface sampling process. This article is a U.S. Government work and is
      in the public domain in the USA.

PMID- 24861608
TI  - Application of the Exactive Plus EMR for automated protein-ligand screening by
      non-covalent mass spectrometry.
AB  - RATIONALE: Non-covalent mass spectrometry (MS) offers considerable potential for
      protein-ligand screening in drug discovery programmes. However, there are some
      limitations with the time-of-flight (TOF) instrumentation typically employed that
      restrict the application of non-covalent MS in industrial laboratories. METHODS:
      An Exactive Plus EMR mass spectrometer was investigated for its ability to
      characterise non-covalent protein-small molecule interactions. Nano-electrospray
      ionisation (nanoESI) infusion was achieved with a TriVersa NanoMate. The
      transport multipole and ion lens voltages, dissociation energies and pressure in
      the OrbitrapTM were optimised. Native MS was performed, with ligand titrations to
      judge retention of protein-ligand interactions, serial dilutions of native
      proteins as an indication of sensitivity, and a heterogeneous protein analysed
      for spectral resolution. RESULTS: Interactions between native proteins and
      ligands are preserved during analysis on the Exactive Plus EMR, with the binding
      affinities determined in good agreement with expected values. High spectral
      resolution allows baseline separation of adduct ions, which should improve the
      accuracy and limit of detection for measuring ligand interactions. Data are also
      presented showing baseline resolution of glycoforms of a highly glycosylated
      protein, allowing binding of a fragment molecule to be detected. CONCLUSIONS: The
      high sensitivity and spectral resolution achievable with the Orbitrap technology
      confer significant advantages over TOF mass spectrometers, and offer a solution
      to current limitations regarding throughput, data analysis and sample
      requirements. A further benefit of improved spectral resolution is the
      possibility of using heterogeneous protein samples such as glycoproteins for
      fragment screening. This would significantly expand the scope of applicability of
      non-covalent MS in the pharmaceutical and other industries.

PMID- 24861609
TI  - An envisioning about the caring in listening.
AB  - The purpose of this article is to make visible further dimensions and uncover an
      envisioning about the caring in listening in the field of caring science, which
      may improve the care for the suffering human being, the patient. Eriksson's
      caritative theory of caring constitutes the starting point for this search for
      knowledge, while the research method is realised by a hermeneutic reading based
      on the philosopher of hermeneutics, Gadamer's thought. The research is realised
      by a reading of Fyodor Dostoyevsky's literary works. The literary characters
      Sonia in Crime and Punishment and Alyosha in The Brothers Karamazov, uncovers
      patterns of meaning-bearing units towards the caring and the interpretation of a
      more profound envisioning about the caring in listening. The uncovering and
      interpretation show that patients in their suffering long to meet a caregiver who
      listens without the least condemnation in their eyes and demeanour. Patients need
      a listening caregiver who shows compassion and who has the courage to remain in
      the struggle of suffering and to carry the patients through insupportable pain,
      guilt and shame. Through listening, it is possible to reawaken a numb heart, to
      take individuals who have gone through a good deal of suffering, from darkness,
      degradation, unendurable pain to the light and to awaken their zest for life and
      joy to live. Listening renews, delivers and transforms human beings so that they
      can begin to find a new direction in life and start living a life in accordance
      with their own fundamental order, purpose, essential decision and individuality.
      Listening takes patients out of their loneliness and unbearable suffering into
      communion and a life worth living. 

PMID- 24861610
TI  - Depressive symptoms are associated with fasting insulin resistance in obese
      youth.
AB  - BACKGROUND: In adults, depressive symptoms are positively associated with insulin
      resistance. OBJECTIVE: To determine whether an association exists between
      depressive symptoms and markers of insulin resistance in youth. METHODS: This
      study used a retrospective review of data from an obesity clinic. We evaluated
      the association between depressive symptoms (Children's Depression Inventory,
      CDI) and fasting insulin and homeostatic model assessment-insulin resistance
      (HOMA-IR) in obese youth (n = 207, age 10-18 years). Individuals with lower vs.
      higher CDI T-scores (<65 vs. >=65) were compared; this cut-point is accepted as
      indicating the possibility of clinical depression. Multiple linear regression was
      used to evaluate relationships between CDI T-scores and insulin resistance.
      RESULTS: Fasting insulin and HOMA-IR values were 40% higher in patients with
      higher CDI T-scores (P = 0.04). After accounting for gender, race, age and body
      mass index, CDI T-score remained associated with HOMA-IR, although the strength
      of the association was small (b = 0.007, P = 0.049). CONCLUSIONS: Relationships
      between depressive symptoms and insulin resistance should be considered when
      evaluating obese youth.

PMID- 24861611
TI  - [(3) H]-L685,458 binding sites are abundant in multiple peripheral organs in
      rats: implications for safety assessment of putative gamma-secretase targeting
      drugs.
AB  - gamma-Secretase is a multimeric enzyme complex that carries out proteolytic
      processing to a variety of cellular proteins. It is currently explored as a
      therapeutic target for Alzheimer's disease (AD) and cancer. Mechanism-based
      toxicity needs to be thoroughly evaluated for gamma-secretase inhibitory and/or
      modulatory drugs. This study comparatively assessed putative gamma-secretase
      catalytic sites in rat peripheral tissues relative to brain and explored an
      effort of its pharmacological inhibition on hair regeneration. Using [(3) H]
      labelled L685,458, a potent gamma-secretase inhibitor, as probe, we found more
      abundant presence of gamma-secretase binding sites in the liver, gastrointestinal
      tract, hair follicle, pituitary gland, ovary and testis, as compared to the
      brain. Local application of L658,458 delayed vibrissal regrowth following whisker
      removal. These results suggest that gamma-secretase may execute important
      biological functions in many peripheral systems, as in the brain. The development
      of gamma-secretase inhibitors/modulators for AD and cancer therapy should include
      close monitoring of toxicological panels for hepatic, gastrointestinal,
      endocrinal and reproductive functions. 

PMID- 24861612
TI  - Salicylamide cocrystals: screening, crystal structure, sublimation
      thermodynamics, dissolution, and solid-state DFT calculations.
AB  - A new cocrystal of 2-hydroxybenzamide (A) with 4-acetamidobenzoic acid (B) has
      been obtained by the DSC screening method. Thermophysical analysis of the
      aggregate [A:B] has been conducted and a fusion diagram has been plotted.
      Cocrystal formation from melts was studied by using thermomicroscopy. A cocrystal
      single-crystal was grown and its crystal structure was determined. The pattern of
      noncovalent interactions has been quantified using the solid-state DFT
      computations coupled with the Bader analysis of the periodic electron density.
      The sublimation processes of A-B cocrystal have been studied and its
      thermodynamic functions have been calculated. The classical method of substance
      transfer by inert gas-carrier was chosen to investigate sublimation processes
      experimentally. The lattice energy is found to be 143 +/- 4 kJ/mol. It is lower
      than the sum of the corresponding values of the cocrystal pure components. The
      theoretical value of the lattice energy, 156 kJ/mol, is in reasonable agreement
      with the experimental one. A ternary phase diagram of solubility (A-B-ethanol)
      has been plotted and the areas with solutions for growing thermodynamically
      stable cocrystals have been determined. 

PMID- 24861614
TI  - Intrinsic rewards experienced by a group of dentists working with underserved
      populations.
AB  - BACKGROUND: The aim of this study was to explore, using qualitative methods, the
      intrinsic reasons why dentists work with underserved groups. Minority and
      marginalized groups of Australians suffer a greater burden of dental disease than
      the general population due to disparities in accessing care. Recruitment and
      retention of dentists to care for underserved groups is problematic due to
      personal, professional and structural reasons. What drives dentists to work with
      underserved groups is not widely known. METHODS: Sixteen dentists were recruited
      using 'snowball' purposeful sampling. Semi-structured in-depth interviews were
      conducted. Thematic analysis was conducted on the transcriptions to identify
      themes. RESULTS: Five key themes emerged: (1) 'tapped on the shoulder', being
      personally approached or invited; (2) 'dental school experience', the challenges
      faced as a student; (3) 'empathic concern', the non-judgemental expressions of
      care toward others; (4) 'resilience', the ability to bounce back after setbacks;
      (5) 'intrinsic reward', the personal gain and satisfaction received. This study
      focuses on the intrinsic rewards which were found to be simple, unexpected, and
      associated with relieving pain, community engagement and making a difference.
      CONCLUSIONS: Emphasizing personal fulfilment and intrinsic reward could be useful
      when promoting dentistry as a career and when encouraging graduates to consider
      working with disadvantaged groups.

PMID- 24861613
TI  - Risk of positive nonsentinel nodes in women with 1-2 positive sentinel nodes
      related to age and molecular subtype approximated by receptor status.
AB  - We examine risk of positive nonsentinel axillary nodes (NSN) and >=4 positive
      nodes in patients with 1-2 positive sentinel nodes (SN) by age and tumor subtype
      approximated by ER, PR, and Her2 receptor status. Review of two institutional
      databases demonstrated 284 women undergoing breast conservation between 1997 and
      2008 for T1-2 tumors and 1 (229) or 2 (55) positive SN followed by completion
      dissection. The median number of SN and total axillary nodes removed were 2
      (range 1-10) and 14 (range 6-37), respectively. The rate of positive NSNs (p =
      0.5) or >=4 positive nodes (p = 0.6) was not associated with age. NSN were
      positive in 36% of luminal A, 26% of luminal B, 21% of TN and 38% of Her2+ (p =
      0.4). Four or more nodes were present in 17% of luminal A, 13% luminal of B, 0%
      of TN and 29% of Her2+ (p = 0.1). Microscopic extracapsular extension was
      significantly associated with having NSNs positive (55% versus 24%, p < 0.0001)
      and with having total >=4 nodes positive (33% versus 7%, p < 0.0001). In a
      population that was largely eligible for ACOSOG Z0011, the risk of positive NSN
      or >=4 positive nodes did not vary significantly by age. The TN subgroup had the
      lowest risk of both positive NSN or >=4 positive nodes. Several high risk groups
      with >15% risk for having >=4 positive nodes were identified. Further data is
      needed to confirm that ACOSOG Z0011 results are equally applicable to all
      molecular phenotypes.

PMID- 24861615
TI  - PIQMIe: a web server for semi-quantitative proteomics data management and
      analysis.
AB  - We present the Proteomics Identifications and Quantitations Data Management and
      Integration Service or PIQMIe that aids in reliable and scalable data management,
      analysis and visualization of semi-quantitative mass spectrometry based
      proteomics experiments. PIQMIe readily integrates peptide and (non-redundant)
      protein identifications and quantitations from multiple experiments with
      additional biological information on the protein entries, and makes the linked
      data available in the form of a light-weight relational database, which enables
      dedicated data analyses (e.g. in R) and user-driven queries. Using the web
      interface, users are presented with a concise summary of their proteomics
      experiments in numerical and graphical forms, as well as with a searchable
      protein grid and interactive visualization tools to aid in the rapid assessment
      of the experiments and in the identification of proteins of interest. The web
      server not only provides data access through a web interface but also supports
      programmatic access through RESTful web service. The web server is available at
      http://piqmie.semiqprot-emc.cloudlet.sara.nl or
      http://www.bioinformatics.nl/piqmie. This website is free and open to all users
      and there is no login requirement. 

PMID- 24861616
TI  - ProBiS-ligands: a web server for prediction of ligands by examination of protein
      binding sites.
AB  - The ProBiS-ligands web server predicts binding of ligands to a protein structure.
      Starting with a protein structure or binding site, ProBiS-ligands first
      identifies template proteins in the Protein Data Bank that share similar binding
      sites. Based on the superimpositions of the query protein and the similar binding
      sites found, the server then transposes the ligand structures from those sites to
      the query protein. Such ligand prediction supports many activities, e.g. drug
      repurposing. The ProBiS-ligands web server, an extension of the ProBiS web
      server, is open and free to all users at http://probis.cmm.ki.si/ligands. 

PMID- 24861617
TI  - CHOPCHOP: a CRISPR/Cas9 and TALEN web tool for genome editing.
AB  - Major advances in genome editing have recently been made possible with the
      development of the TALEN and CRISPR/Cas9 methods. The speed and ease of
      implementing these technologies has led to an explosion of mutant and transgenic
      organisms. A rate-limiting step in efficiently applying TALEN and CRISPR/Cas9
      methods is the selection and design of targeting constructs. We have developed an
      online tool, CHOPCHOP (https://chopchop.rc.fas.harvard.edu), to expedite the
      design process. CHOPCHOP accepts a wide range of inputs (gene identifiers,
      genomic regions or pasted sequences) and provides an array of advanced options
      for target selection. It uses efficient sequence alignment algorithms to minimize
      search times, and rigorously predicts off-target binding of single-guide RNAs
      (sgRNAs) and TALENs. Each query produces an interactive visualization of the gene
      with candidate target sites displayed at their genomic positions and color-coded
      according to quality scores. In addition, for each possible target site,
      restriction sites and primer candidates are visualized, facilitating a
      streamlined pipeline of mutant generation and validation. The ease-of-use and
      speed of CHOPCHOP make it a valuable tool for genome engineering. 

PMID- 24861618
TI  - RAMICS: trainable, high-speed and biologically relevant alignment of high
      throughput sequencing reads to coding DNA.
AB  - The challenge presented by high-throughput sequencing necessitates the
      development of novel tools for accurate alignment of reads to reference
      sequences. Current approaches focus on using heuristics to map reads quickly to
      large genomes, rather than generating highly accurate alignments in coding
      regions. Such approaches are, thus, unsuited for applications such as amplicon
      based analysis and the realignment phase of exome sequencing and RNA-seq, where
      accurate and biologically relevant alignment of coding regions is critical. To
      facilitate such analyses, we have developed a novel tool, RAMICS, that is
      tailored to mapping large numbers of sequence reads to short lengths (<10 000 bp)
      of coding DNA. RAMICS utilizes profile hidden Markov models to discover the open
      reading frame of each sequence and aligns to the reference sequence in a
      biologically relevant manner, distinguishing between genuine codon-sized indels
      and frameshift mutations. This approach facilitates the generation of highly
      accurate alignments, accounting for the error biases of the sequencing machine
      used to generate reads, particularly at homopolymer regions. Performance
      improvements are gained through the use of graphics processing units, which
      increase the speed of mapping through parallelization. RAMICS substantially
      outperforms all other mapping approaches tested in terms of alignment quality
      while maintaining highly competitive speed performance. 

PMID- 24861619
TI  - Bookmarking promoters in mitotic chromatin: poly(ADP-ribose)polymerase-1 as an
      epigenetic mark.
AB  - Epigenetics are the heritable changes in gene expression or cellular phenotype
      caused by mechanisms other than changes in the underlying DNA sequence. After
      mitosis, it is thought that bookmarking transcription factors remain at
      promoters, regulating which genes become active and which remain silent. Herein,
      we demonstrate that poly(ADP-ribose)polymerase-1 (PARP-1) is a genome-wide
      epigenetic memory mark in mitotic chromatin, and we further show that the
      presence of PARP-1 is absolutely crucial for reactivation of transcription after
      mitosis. Based on these findings, a novel molecular model of epigenetic memory
      transmission through the cell cycle is proposed. 

PMID- 24861620
TI  - Engineering an Acinetobacter regulon for biosensing and high-throughput enzyme
      screening in E. coli via flow cytometry.
AB  - We created a single cell sorting system to screen for enzyme activity in
      Escherichia coli producing 3,4 dihydroxy benzoate (34DHB). To do so, we
      engineered a transcription factor regulon controlling the expression of green
      fluorescent protein (GFP) for induction by 34DHB. An autoregulated transcription
      factor, pcaU, was borrowed from Acinetobacter sp ADP1 to E. coli and its promoter
      region adapted for activity in E. Coli. The engineered pcaU regulon was inducible
      at >5 MUM exogenous 34DHB, making it a sensitive biosensor for this industrially
      significant nylon precursor. Addition of a second plasmid provided IPTG inducible
      expression of dehydroshikimate dehydratase enzyme (AsbF), which converts
      endogenous dehydroshikimate to 34DHB. This system produced GFP fluorescence in an
      IPTG dose-dependent manner, and was easily detected in single cell on flow
      cytometer despite a moderate catalytic efficiency of AsbF. Using fluorescence
      activated cell sorting (FACS), individual cells carrying the active AsbF could be
      isolated even when diluted into a decoy population of cells carrying a mutant
      (inactivated) AsbF variant at one part in a million. The same biosensor was also
      effective for further optimization of itself. FACS on E. coli carrying randomized
      loci in the promoter showed several variants with enhanced response to 34DHB. 

PMID- 24861621
TI  - NetworkAnalyst--integrative approaches for protein-protein interaction network
      analysis and visual exploration.
AB  - Biological network analysis is a powerful approach to gain systems-level
      understanding of patterns of gene expression in different cell types, disease
      states and other biological/experimental conditions. Three consecutive steps are
      required--identification of genes or proteins of interest, network construction
      and network analysis and visualization. To date, researchers have to learn to use
      a combination of several tools to accomplish this task. In addition, interactive
      visualization of large networks has been primarily restricted to locally
      installed programs. To address these challenges, we have developed
      NetworkAnalyst, taking advantage of state-of-the-art web technologies, to enable
      high performance network analysis with rich user experience. NetworkAnalyst
      integrates all three steps and presents the results via a powerful online network
      visualization framework. Users can upload gene or protein lists, single or
      multiple gene expression datasets to perform comprehensive gene annotation and
      differential expression analysis. Significant genes are mapped to our manually
      curated protein-protein interaction database to construct relevant networks. The
      results are presented through standard web browsers for network analysis and
      interactive exploration. NetworkAnalyst supports common functions for network
      topology and module analyses. Users can easily search, zoom and highlight nodes
      or modules, as well as perform functional enrichment analysis on these
      selections. The networks can be customized with different layouts, colors or node
      sizes, and exported as PNG, PDF or GraphML files. Comprehensive FAQs, tutorials
      and context-based tips and instructions are provided. NetworkAnalyst currently
      supports protein-protein interaction network analysis for human and mouse and is
      freely available at http://www.networkanalyst.ca.

PMID- 24861622
TI  - MORPHIN: a web tool for human disease research by projecting model organism
      biology onto a human integrated gene network.
AB  - Despite recent advances in human genetics, model organisms are indispensable for
      human disease research. Most human disease pathways are evolutionally conserved
      among other species, where they may phenocopy the human condition or be
      associated with seemingly unrelated phenotypes. Much of the known gene-to
      phenotype association information is distributed across diverse databases,
      growing rapidly due to new experimental techniques. Accessible bioinformatics
      tools will therefore facilitate translation of discoveries from model organisms
      into human disease biology. Here, we present a web-based discovery tool for human
      disease studies, MORPHIN (model organisms projected on a human integrated gene
      network), which prioritizes the most relevant human diseases for a given set of
      model organism genes, potentially highlighting new model systems for human
      diseases and providing context to model organism studies. Conceptually, MORPHIN
      investigates human diseases by an orthology-based projection of a set of model
      organism genes onto a genome-scale human gene network. MORPHIN then prioritizes
      human diseases by relevance to the projected model organism genes using two
      distinct methods: a conventional overlap-based gene set enrichment analysis and a
      network-based measure of closeness between the query and disease gene sets
      capable of detecting associations undetectable by the conventional overlap-based
      methods. MORPHIN is freely accessible at http://www.inetbio.org/morphin. 

PMID- 24861623
TI  - Quantitative telomerase enzyme activity determination using droplet digital PCR
      with single cell resolution.
AB  - The telomere repeat amplification protocol (TRAP) for the human reverse
      transcriptase, telomerase, is a PCR-based assay developed two decades ago and is
      still used for routine determination of telomerase activity. The TRAP assay can
      only reproducibly detect ~ 2-fold differences and is only quantitative when
      compared to internal standards and reference cell lines. The method generally
      involves laborious radioactive gel electrophoresis and is not conducive to high
      throughput analyzes. Recently droplet digital PCR (ddPCR) technologies have
      become available that allow for absolute quantification of input deoxyribonucleic
      acid molecules following PCR. We describe the reproducibility and provide several
      examples of a droplet digital TRAP (ddTRAP) assay for telomerase activity,
      including quantitation of telomerase activity in single cells, telomerase
      activity across several common telomerase positive cancer cells lines and in
      human primary peripheral blood mononuclear cells following mitogen stimulation.
      Adaptation of the TRAP assay to digital format allows accurate and reproducible
      quantification of the number of telomerase-extended products (i.e. telomerase
      activity; 57.8 +/- 7.5) in a single HeLa cell. The tools developed in this study
      allow changes in telomerase enzyme activity to be monitored on a single cell
      basis and may have utility in designing novel therapeutic approaches that target
      telomerase.

PMID- 24861624
TI  - Enhancing UCSF Chimera through web services.
AB  - Integrating access to web services with desktop applications allows for an
      expanded set of application features, including performing computationally
      intensive tasks and convenient searches of databases. We describe how we have
      enhanced UCSF Chimera (http://www.rbvi.ucsf.edu/chimera/), a program for the
      interactive visualization and analysis of molecular structures and related data,
      through the addition of several web services
      (http://www.rbvi.ucsf.edu/chimera/docs/webservices.html). By streamlining access
      to web services, including the entire job submission, monitoring and retrieval
      process, Chimera makes it simpler for users to focus on their science projects
      rather than data manipulation. Chimera uses Opal, a toolkit for wrapping
      scientific applications as web services, to provide scalable and transparent
      access to several popular software packages. We illustrate Chimera's use of web
      services with an example workflow that interleaves use of these services with
      interactive manipulation of molecular sequences and structures, and we provide an
      example Python program to demonstrate how easily Opal-based web services can be
      accessed from within an application. Web server availability:
      http://webservices.rbvi.ucsf.edu/opal2/dashboard?command=serviceList. 

PMID- 24861626
TI  - A web tool for the design and management of panels of genes for targeted
      enrichment and massive sequencing for clinical applications.
AB  - Disease targeted sequencing is gaining importance as a powerful and cost
      effective application of high throughput sequencing technologies to the
      diagnosis. However, the lack of proper tools to process the data hinders its
      extensive adoption. Here we present TEAM, an intuitive and easy-to-use web tool
      that fills the gap between the predicted mutations and the final diagnostic in
      targeted enrichment sequencing analysis. The tool searches for known diagnostic
      mutations, corresponding to a disease panel, among the predicted patient's
      variants. Diagnostic variants for the disease are taken from four databases of
      disease-related variants (HGMD-public, HUMSAVAR, ClinVar and COSMIC.) If no
      primary diagnostic variant is found, then a list of secondary findings that can
      help to establish a diagnostic is produced. TEAM also provides with an interface
      for the definition of and customization of panels, by means of which, genes and
      mutations can be added or discarded to adjust panel definitions. TEAM is freely
      available at: http://team.babelomics.org. 

PMID- 24861625
TI  - Hyperactive Cdc2 kinase interferes with the response to broken replication forks
      by trapping S.pombe Crb2 in its mitotic T215 phosphorylated state.
AB  - Although it is well established that Cdc2 kinase phosphorylates the DNA damage
      checkpoint protein Crb2(53BP1) in mitosis, the full impact of this modification
      is still unclear. The Tudor-BRCT domain protein Crb2 binds to modified histones
      at DNA lesions to mediate the activation of Chk1 by Rad3ATR kinase. We
      demonstrate here that fission yeast cells harbouring a hyperactive Cdc2CDK1
      mutation (cdc2.1w) are specifically sensitive to the topoisomerase 1 inhibitor
      camptothecin (CPT) which breaks DNA replication forks. Unlike wild-type cells,
      which delay only briefly in CPT medium by activating Chk1 kinase, cdc2.1w cells
      bypass Chk1 to enter an extended cell-cycle arrest which depends on Cds1 kinase.
      Intriguingly, the ability to bypass Chk1 requires the mitotic Cdc2
      phosphorylation site Crb2-T215. This implies that the presence of the mitotic
      phosphorylation at Crb2-T215 channels Rad3 activity towards Cds1 instead of Chk1
      when forks break in S phase. We also provide evidence that hyperactive Cdc2.1w
      locks cells in a G1-like DNA repair mode which favours non-homologous end joining
      over interchromosomal recombination. Taken together, our data support a model
      such that elevated Cdc2 activity delays the transition of Crb2 from its G1 to its
      G2 mode by blocking Srs2 DNA helicase and Casein Kinase 1 (Hhp1).

PMID- 24861627
TI  - TCP1 complex proteins interact with phosphorothioate oligonucleotides and can co
      localize in oligonucleotide-induced nuclear bodies in mammalian cells.
AB  - Phosphorothioate (PS) antisense oligonucleotides (ASOs) have been successfully
      developed as drugs to reduce the expression of disease-causing genes. PS-ASOs can
      be designed to induce degradation of complementary RNAs via the RNase H pathway
      and much is understood about that process. However, interactions of PS-ASOs with
      other cellular proteins are not well characterized. Here we report that in cells
      transfected with PS-ASOs, the chaperonin T-complex 1 (TCP1) proteins interact
      with PS-ASOs and enhance antisense activity. The TCP1-beta subunit co-localizes
      with PS-ASOs in distinct nuclear structures, termed phosphorothioate bodies or PS
      bodies. Upon Ras-related nuclear protein (RAN) depletion, cytoplasmic PS-body
      like structures were observed and nuclear concentrations of PS-ASOs were reduced,
      suggesting that TCP1-beta can interact with PS-ASOs in the cytoplasm and that the
      nuclear import of PS-ASOs is at least partially through the RAN-mediated pathway.
      Upon free uptake, PS-ASOs co-localize with TCP1 proteins in cytoplasmic foci
      related to endosomes/lysosomes. Together, our results indicate that the TCP1
      complex binds oligonucleotides with TCP1-beta subunit being a nuclear PS-body
      component and suggest that the TCP1 complex may facilitate PS-ASO uptake and/or
      release from the endocytosis pathway. 

PMID- 24861628
TI  - COUGER--co-factors associated with uniquely-bound genomic regions.
AB  - Most transcription factors (TFs) belong to protein families that share a common
      DNA binding domain and have very similar DNA binding preferences. However, many
      paralogous TFs (i.e. members of the same TF family) perform different regulatory
      functions and interact with different genomic regions in the cell. A potential
      mechanism for achieving this differential in vivo specificity is through
      interactions with protein co-factors. Computational tools for studying the
      genomic binding profiles of paralogous TFs and identifying their putative co
      factors are currently lacking. Here, we present an interactive web implementation
      of COUGER, a classification-based framework for identifying protein co-factors
      that might provide specificity to paralogous TFs. COUGER takes as input two sets
      of genomic regions bound by paralogous TFs, and it identifies a small set of
      putative co-factors that best distinguish the two sets of sequences. To achieve
      this task, COUGER uses a classification approach, with features that reflect the
      DNA-binding specificities of the putative co-factors. The identified co-factors
      are presented in a user-friendly output page, together with information that
      allows the user to understand and to explore the contributions of individual co
      factor features. COUGER can be run as a stand-alone tool or through a web
      interface: http://couger.oit.duke.edu. 

PMID- 24861629
TI  - Epigenetics in radiotherapy: where are we heading?
AB  - Radiotherapy is an important component of anti-cancer treatment. However, not all
      cancer patients respond to radiotherapy, and with current knowledge clinicians
      are unable to predict which patients are at high risk of recurrence after
      radiotherapy. There is therefore an urgent need for biomarkers to guide clinical
      decision-making. Although the importance of epigenetic alterations is widely
      accepted, their application as biomarkers in radiotherapy has not been studied
      extensively. In addition, it has been suggested that radiotherapy itself
      introduces epigenetic alterations. As epigenetic alterations can potentially be
      reversed by drug treatment, they are interesting candidate targets for anticancer
      therapy or radiotherapy sensitizers. The application of demethylating drugs or
      histone deacetylase inhibitors to sensitize patients for radiotherapy has been
      studied in vitro, in vivo as well as in clinical trials with promising results.
      This review describes the current knowledge on epigenetics in radiotherapy.

PMID- 24861630
TI  - In vivo portal dosimetry for head-and-neck VMAT and lung IMRT: linking gamma
      analysis with differences in dose-volume histograms of the PTV.
AB  - PURPOSE: To relate the results of gamma-analysis and dose-volume histogram (DVH)
      analysis of the PTV for detecting dose deviations with in vivo dosimetry for two
      treatment sites. METHODS AND MATERIALS: In vivo 3D dose distributions were
      reconstructed for 722 fractions of 200 head-and-neck (H&N) VMAT treatments and
      183 fractions of 61 lung IMRT plans. The reconstructed and planned dose
      distributions in the PTV were compared using (a) the gamma-distribution and (b)
      the differences in D2, D50 and D98 between the two dose distributions. Using pre
      defined tolerance levels, all fractions were classified as deviating or not
      deviating by both methods. The mutual agreement, the sensitivity and the
      specificity of the two methods were compared. RESULTS: For lung IMRT, the
      classification of the fractions was nearly identical for gamma- and DVH-analyses
      of the PTV (94% agreement) and the sensitivity and specificity were comparable
      for both methods. Less agreement (80%) was found for H&N VMAT, while gamma
      analysis was both less sensitive and less specific. CONCLUSIONS: DVH- and gamma
      analyses perform nearly equal in finding dose deviations in the PTV for lung IMRT
      treatments; for H&N VMAT treatments, DVH-analysis is preferable. As a result of
      this study, a smooth transition to using DVH-analysis clinically for detecting in
      vivo dose deviations in the PTV is within reach.

PMID- 24861631
TI  - Outcome impact and cost-effectiveness of quality assurance for radiotherapy
      planned for the EORTC 22071-24071 prospective study for head and neck cancer.
AB  - INTRODUCTION: One of the goals of Quality Assurance in Radiotherapy (QART) is to
      reduce the variability and uncertainties related to treatment planning and beam
      delivery. The purpose of this study was to assess the outcome impact and cost
      effectiveness (CE) of various QART levels for a head and neck (H&N) cancer study.
      MATERIALS AND METHODS: QART levels were defined as: basic QART with a dummy run
      (level 2), level 2 plus prospective Individual Case Reviews (ICRs) for 15% of
      patients (level 3) and level 2 plus prospective ICRs for all patients (level 4).
      The follow-up of patients was modeled using a multi-state model with parameters
      derived from EORTC, TROG and RTOG prospective studies. Individual patient data,
      linking QART results with outcome, were retrieved from the TROG database. Results
      for each QART level were expressed as percentage of mortality and local failure
      at 5 years. RESULTS: Quality-of-life-adjusted and recurrence-free survival
      increased with increasing QART levels. The increase of all these metrics was more
      sizeable with an increased QART level from 2 or 3 to 4. The estimated quality
      adjusted-life-years (QALYs) for an increase of QART levels of 3-4 and 2-4 were
      0.09 and 0.15, respectively. The incremental CE ratio was ?5525 and ?3659 Euros
      per QALY for these QART levels. Compared to QART level 2 or 3, level 4 was cost
      effective. CONCLUSIONS: Increasing QART levels resulted in better patient outcome
      in this simulated study. The increased complexity of the QART program was also
      cost-effective.

PMID- 24861632
TI  - Intra-limb coordination while walking is affected by cognitive load and walking
      speed.
AB  - Knowledge about intra-limb coordination (ILC) during challenging walking
      conditions provides insight into the adaptability of central nervous system (CNS)
      for controlling human gait. We assessed the effects of cognitive load and speed
      on the pattern and variability of the ILC in young people during walking. Thirty
      healthy young people (19 female and 11 male) participated in this study. They
      were asked to perform 9 walking trials on a treadmill, including walking at three
      paces (preferred, slower and faster) either without a cognitive task (single-task
      walking) or while subtracting 1's or 3's from a random three-digit number (simple
      and complex dual-task walking, respectively). Deviation phase (DP) and mean
      absolute relative phase (MARP) values-indicators of variability and phase dynamic
      of ILC, respectively-were calculated using the data collected by a motion capture
      system. We used a two-way repeated measure analysis of variance for statistical
      analysis. The results showed that cognitive load had a significant main effect on
      DP of right shank-foot and thigh-shank, left shank-foot and pelvis-thigh
      (p<0.05), and MARP of both thigh-shank segments (p<0.01). In addition, the main
      effect of walking speed was significant on DP of all segments in each side and
      MARP of both thigh-shank and pelvis-thigh segments (p<0.001). The interaction of
      cognitive load and walking speed was only significant for MARP values of left
      shank-foot and right pelvis-thigh (p<0.05 and p<0.001, respectively). We suggest
      that cognitive load and speed could significantly affect the ILC and variability
      and phase dynamic during walking. 

PMID- 24861633
TI  - Peak systolic or maximum intra-aneurysmal hemodynamic condition? Implications on
      normalized flow variables.
AB  - BACKGROUND: CFD has been used to assess intra-aneurysmal hemodynamics.
      Nevertheless, the lack of patient-specific flow information has triggered the
      possibility of implementing a wide variety of physiological flow conditions. Due
      to these uncertainties in the patient flow conditions, the normalization of the
      intra-aneurysmal hemodynamics is generally conducted. PURPOSE: To investigate how
      intra-aneurysmal and arterial hemodynamics change over time when different
      physiological flow conditions are imposed. MATERIAL AND METHOD: Eleven image
      based aneurysm models were used in this study. CFD simulations were performed
      under pulsatile flows. Velocity magnitude and wall shear stress (WSS) were
      calculated during one cardiac cycle. RESULTS: Maximum hemodynamic condition does
      not necessarily occurred at peak systole. The shifted time from peak systole to
      the time where the maximum hemodynamic condition occurs inside the aneurysm
      depends on the aneurysm size, flow rate, surrounding vasculature and the
      stabilities of flow patterns. Larger shifted times were observed with increasing
      aneurysm size as well as with reducing the flow rate. Moreover, the maximum
      hemodynamic condition can occur earlier than peak systole if flow patterns at
      parent artery change. Differences between peak systolic WSS and maximum WSS can
      be up to 65%. Moreover, the velocity magnitude and WSS depend on the selected
      segment of the parent artery, with relatively larger variability near peak
      systole than the rest of the cardiac cycle. More than 50% of differences were
      found between two arterial segments arbitrary selected for a given flow rate.
      CONCLUSIONS: Our results indicate that if the highest intra-aneurysmal stress is
      calculated, then it is preferable to use the time instance where the maximum WSS
      occurred instead of the peak systolic WSS. Additionally, the normalization of
      intra-aneurysmal hemodynamics should be done with variables that do not depend on
      any arbitrary segment of the parent artery.

PMID- 24861634
TI  - A statistical human rib cage geometry model accounting for variations by age,
      sex, stature and body mass index.
AB  - In this study, we developed a statistical rib cage geometry model accounting for
      variations by age, sex, stature and body mass index (BMI). Thorax CT scans were
      obtained from 89 subjects approximately evenly distributed among 8 age groups and
      both sexes. Threshold-based CT image segmentation was performed to extract the
      rib geometries, and a total of 464 landmarks on the left side of each subject's
      ribcage were collected to describe the size and shape of the rib cage as well as
      the cross-sectional geometry of each rib. Principal component analysis and
      multivariate regression analysis were conducted to predict rib cage geometry as a
      function of age, sex, stature, and BMI, all of which showed strong effects on rib
      cage geometry. Except for BMI, all parameters also showed significant effects on
      rib cross-sectional area using a linear mixed model. This statistical rib cage
      geometry model can serve as a geometric basis for developing a parametric human
      thorax finite element model for quantifying effects from different human
      attributes on thoracic injury risks. 

PMID- 24861635
TI  - Neuroinflammation: good, bad, or indifferent?

PMID- 24861636
TI  - Development of a frequency-separated knob with variable change rates by rotation
      speed.
AB  - The principle of frequency separation is a design method to display different
      information or feedback in accordance with the frequency of interaction between
      users and systems. This principle can be usefully applied to the design of knobs.
      Particularly, their rotation speed can be a meaningful criterion for applying the
      principle. Hence a knob can be developed, which shows change rates varying
      depending on its rotation speed. Such a knob would be more efficient than
      conventional knobs with constant change rate. We developed a prototype of
      frequency-separated knobs that has different combinations of the number of
      rotation speed steps and the size of the variation of change rate. With this
      prototype, we conducted an experiment to examine whether a speed frequency
      separated knob enhances users' task performance. The results showed that the
      newly designed knob was effective in enhancing task performance, and that task
      efficiency was the best when its change rate increases exponentially and its
      rotation speed has three steps. We conducted another experiment to investigate
      how a more rapid exponential increase of change rate and a more number of steps
      of rotation speed influence users' task performance. The results showed that
      merely increasing both the size of the variation of change rates and the number
      of speed steps did not result in better task performance. Although two
      experimental results cannot easily be generalized to other contexts, they still
      offer practical information useful for designing a speed frequency-separated knob
      in various consumer electronics and control panels of industrial systems. 

PMID- 24861637
TI  - Ampelopsin suppresses breast carcinogenesis by inhibiting the mTOR signalling
      pathway.
AB  - The mammalian target of rapamycin (mTOR), which is a master regulator of cellular
      catabolism and anabolism, plays an important role in tumourigenesis and
      progression. In this study, we report the chemopreventive effect of the dietary
      compound ampelopsin (AMP) on breast carcinogenesis in vivo and in vitro, which
      acts by inhibiting the mTOR signalling pathway. Our study indicates that AMP
      treatment effectively suppresses 1-methyl-1-nitrosourea (MNU)-induced breast
      carcinogenesis in rats and inhibits 4-(methylnitrosamino)-1-(3-pyridyl)-1
      butanone (NNK) and benzo[a]pyrene (B[a]P)-induced cellular carcinogenesis.
      Additionally, AMP inhibits the growth of breast cancer cells in vitro and in
      vivo. The activity of mTOR kinase was found to be significantly increased in a
      time-dependent manner during chronic breast carcinogenesis, and this increase can
      be suppressed by AMP co-treatment. AMP also effectively suppresses mTOR activity
      in breast cancer MDA-MB-231 cells. We also demonstrated that AMP is an effective
      mTOR inhibitor that binds to one site on the mTOR target in two ways. Further
      studies confirmed that AMP inhibits the activation of Akt, suppresses the
      formation of mTOR complexes (mTORC)1/2 by dissociating regulatory-associated
      protein of mTOR and rapamycin-insensitive companion of mTOR and, consequently,
      decreases the activation of the downstream targets of mTOR, including ribosomal
      p70-S6 kinase, ribosomal protein S6, eukaryotic translation initiation factor 4B
      and eukaryotic translation initiation factor 4E-binding protein 1. These finding
      suggest that AMP is a bioactive natural chemopreventive agent against breast
      carcinogenesis and is an effective mTOR inhibitor that may be developed as a
      useful chemotherapeutic agent in the treatment of breast cancer. 

PMID- 24861638
TI  - Temporal trends in stillbirth in the United States, 1992-2004: a population-based
      cohort study.
AB  - OBJECTIVE: To examine temporal trends in stillbirth and its risk factors in the
      United States (US), and to assess the contribution of labour induction and
      caesarean delivery to the stillbirth rate. DESIGN: Population-based cohort study
      based on linked birth-infant death and fetal death data files from the US
      National Vital Statistics System. SETTING: Complete data were available for 44
      states and the District of Columbia. POPULATION OR SAMPLE: Singleton births from
      1992 to 2004. METHODS: We assessed changes in stillbirth rates from 1992-1994 to
      2002-2004 before and after adjustment for changes in maternal characteristics
      including maternal age, education, smoking, and medical risk factors, using Cox
      regression models. We also carried out an ecological study, using states as the
      units of analysis, to assess the impact on the stillbirth rate of increasing
      induction and caesarean delivery. Race-specific subgroup analyses were performed
      and included non-Hispanic Whites and non-Hispanic Blacks. MAIN OUTCOME MEASURE:
      Stillbirth rate. RESULTS: The stillbirth rate among non-Hispanic White singleton
      births decreased 11.5% from 1992-1994 (5.2 per 1000) to 2002-2004 (4.6 per 1000).
      After adjustment for maternal risk factors, the hazard ratio (HR) for 2002-2004
      was 1.01 (0.99, 1.03) for gestational age (GA) <=39 weeks, but 0.92 (0.86, 0.99)
      at 40 or more weeks. The ecologic analysis revealed a nonsignificant negative
      correlation of -0.17 (-0.44, 0.13) between state-level changes in stillbirth at
      GA >=40 weeks and labour induction. A nonsignificant positive correlation of 0.23
      (-0.07, 0.49) was observed between changes in stillbirth at all GAs and caesarean
      delivery and did not differ at GA <=39 versus >=40 weeks. Results were similar
      among non-Hispanic Blacks. CONCLUSIONS: Changes in maternal risk factors
      explained the reduction in stillbirth at GA <=39 weeks but not at >=40 weeks. The
      rise in labour induction and caesarean delivery rates did not explain the
      reduction in stillbirth >=40 weeks of gestation.

PMID- 24861639
TI  - Should we administer an esophageal capsule in the ER?

PMID- 24861640
TI  - Burnout in gastroenterologists and how to prevent it.

PMID- 24861641
TI  - A summary of the 20th International Symposium on Hepatitis C Virus and Related
      Viruses.

PMID- 24861643
TI  - Healthcare associated infections (HAI) perspectives.
AB  - Healthcare associated infections (HAI) are among the major complications of
      modern medical therapy. The most important HAIs are those related to invasive
      devices: central line-associated bloodstream infections (CLABSI), catheter
      associated urinary tract infections (CAUTI), ventilator-associated pneumonia
      (VAP) as well as surgical site infections (SSI). HAIs are associated with
      significant mortality, morbidities and increasing healthcare cost. The cited case
      fatality rate ranges from 2.3% to 14.4% depending on the type of infection. In
      this mini-review, we shed light on these aspects as well as drivers to decrease
      HAIs. 

PMID- 24861642
TI  - Does knowledge about bloodborne pathogens influence the reuse of medical
      injection syringes among women in Pakistan?
AB  - Injections with re-used syringes have been identified as a major risk factor for
      hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in Pakistan. We
      analyzed data from the 2006-2007 Pakistan Demographic Health Survey (PDHS) to
      describe the distribution of injections administered with newly opened syringes
      and assessed the association of knowledge about bloodborne pathogens with syringe
      reuse in Pakistan. In the PDHS, women aged 12-49 years were enrolled through a
      multistage stratified cluster-sampling strategy across Pakistan. Approximately
      10,000 women were interviewed to collect information regarding receiving
      injections, the use of syringes taken out of new unopened packages for their last
      injections, and knowledge regarding the transmission of Human Immunodeficiency
      Virus (HIV), HBV and HCV through the re-use of syringes and transfusion of
      unscreened blood. Of the 5126/10,023 women who provided information concerning
      their last injection, 4342 (86%) received this injection with a new syringe taken
      out of an unopened package. The proportion of injections received with a new
      syringe increased with the education level, wealth, HIV knowledge and knowledge
      about HCV/HBV transmission through the re-use of syringes. In the multivariable
      model, respondents in the 4th (adjusted odds ratio (AOR): 2.1, 95%CI: 1.4-3.0)
      and 5th (AOR: 2.4, 95%CI: 1.6-3.5) wealth quintiles, with some education (AOR:
      1.4, 95%CI: 1.1-1.9), those in the 4th quartile of the HIV knowledge score (AOR:
      1.5, 95%CI: 1.1-2.0), and those with the knowledge that a new syringe protects
      against HCV/HBV and HIV (AOR: 2.3, 95%CI: 1.5-3.5) were more likely to receive
      injections with a newly opened syringe. The patients' knowledge regarding the
      transmission of bloodborne pathogens is an important factor in receiving
      injections with a new syringe. 

PMID- 24861644
TI  - Lower prevalence of hlyD, papC and cnf-1 genes in ciprofloxacin-resistant
      uropathogenic Escherichia coli than their susceptible counterparts isolated from
      southern India.
AB  - OBJECTIVE: The study was conducted to determine the association of the hlyD, papC
      and cnf-1 virulence genes with drug resistance in uropathogenic Escherichia coli
      (UPEC) isolated from cases of urinary tract infection (UTI). METHOD: A total of
      193 E. coli strains isolated from symptomatic cases of UTI in a tertiary care
      teaching hospital in Raichur, Northern Karnataka, India were included in the
      study. The antibiotic susceptibility pattern was determined by Kirby-Bauer's Disk
      Diffusion method, and the strains resistant to any of the third generation
      cephalosporins tested were further confirmed for extended-spectrum beta-lactamase
      (ESBL)-production by an E-strip test. Genotypic virulence markers, namely, hlyD,
      papC and cnf-1, were detected by the uniplex PCR method and the phylogenetic
      characterization was performed by a multiplex PCR assay. RESULTS: The majority of
      the E. coli isolates belonged to the B2 phylogenetic group were significantly
      associated with ciprofloxacin-sensitivity and non-ESBL production (p<0.05). An
      increased prevalence of ciprofloxacin-sensitive strains over ciprofloxacin
      resistant strains were observed among the UPEC isolates harboring the papC (72.9%
      vs. 40.2%; p<0.001), hlyD (43.7% vs. 21.6%; p<0.001) and cnf-1 (30.2% vs. 12.3%;
      p<0.05) genes. The presence of a multivirulent gene in the non-ESBL E. coli
      strains (44.5%) was significantly higher (p<0.05) than in the ESBL-producing
      strains (21%). CONCLUSIONS: Among the UPEC isolates, the predominant B2
      phylogenetic group was significantly associated with the ciprofloxacin-sensitive
      strains, as well as with the non-ESBL E. coli strains. The genotypic virulence
      markers of UPEC were associated with ciprofloxacin-sensitivity, and a significant
      number of the non-ESBL strains harbored multivirulent genes. The relationship
      between the presence of the virulence genes and ESBL production was complex and
      warrants further intensive studies.

PMID- 24861645
TI  - A novel quinoline molecular probe and the derived functionalized gold
      nanoparticles: sensing properties and cytotoxicity studies in MCF-7 human breast
      cancer cells.
AB  - A highly selective quinoline-based fluorescent sensor L was designed, prepared
      and used to monitor zinc ions in Goldfish (Carassius auratus) as model of
      vertebrate organism. Modified gold nanoparticles having functional quinoline
      molecules (GNPs@L) were also synthesized and their sensing properties towards
      different metal ions were also explored in solution, showing high selectively
      towards the toxic and heavy metal ion mercury. Cell proliferation kit XTT that
      employs 2,3-bis-(2-methoxy-4-nitro- 5-sulfophenyl)-2H-tetrazolium-5-carboxanilide
      salt (XTT) was used in order to investigate the cytotoxicity of compound L and
      GNPs@L on the MCF-7 breast cancer cells, showing significant cytotoxicity in
      comparison with similar reported systems. It was observed that L and GNPs@L
      compounds induced apoptosis in MCF-7 cancer cells. The cellular uptake of the
      hybrid system GNPs@L was studied using confocal laser scanning microscopy (CLSM).

PMID- 24861646
TI  - Association of single nucleotide polymorphisms of ERCC1 and XPF with colorectal
      cancer risk and interaction with tobacco use.
AB  - We investigated the association between polymorphisms in excision repair cross
      complementation group 1 (ERCC1) (rs3212986, rs2298881 and rs11615) and xeroderma
      pigmentosum-complementation group F (XPF) (rs2276466 and rs6498486) and risk of
      colorectal cancer. A 1:1 matched case-control study was conducted. Conditional
      regression analysis indicated that individuals carrying the ERCC1 rs3212986 TT
      genotype and T allele had a marginally increased risk of colorectal cancer when
      compared with subjects with the GG genotype. Similarly, subjects carrying the
      rs11615 TT genotype and T allele had a marginally increased risk of colorectal
      cancer when compared with those with the CC genotype. Stratified analysis
      revealed that individuals with rs3212986 TT who were current or former smokers
      had a significantly increased risk of colorectal cancer, and a significant
      interaction was found between this SNP and cigarette smoking. In conclusion, our
      study suggests that rs3212986 and rs11615 polymorphisms are associated with risk
      of colorectal cancer in a Chinese population, particularly in smokers. This
      finding could be useful in revealing the genetic characteristics of colorectal
      cancer, and suggests more effective strategies for prevention and treatment. 

PMID- 24861647
TI  - Intragenic isochores (intrachores) in the platelet phosphofructokinase gene of
      Passeriform birds.
AB  - Total GC-content in the platelet phosphofructokinase gene of Zebra Finch
      (Taeniopygia guttata) is low (37.53+/-0.51%), while there are short areas (about
      300 nucleotides in length) with increased GC-content overlapping its exon 4 and
      exon 17. GC-content in third codon positions (3GC) of those two exons is equal to
      88.42 and 80.00%, respectively, while overall 3GC of the coding region is equal
      to 49.9%. Similar distribution of GC-content has been found in platelet
      phosphofructokinase genes of other birds from Passeriformes order. According to
      the results of phylogenetic analysis, formation of those areas with high G+C
      started from 91.4 to 47.1millionyears ago, since there are no such peaks of GC
      content in homologous genes of other birds and reptiles. There are clusters of
      transcription factor binding sites in those areas with higher GC-content, as well
      as microRNA precursors conserved in Zebra Finch and Flycatcher genes. According
      to our hypothesis those intragenic isochores (intrachores) may be consequences of
      autonomous microRNA precursor transcription at certain period(s) of embryogenesis
      and gametogenesis, when the platelet phosphofructokinase gene itself is not
      expressed. Transcription-associated mutational pressure existing during those
      periods may cause the increase in rates of AT to GC mutations in those genes
      which are transcribed.

PMID- 24861648
TI  - p.Pro4Arg mutation in LMNA gene: a new atypical progeria phenotype without
      metabolism abnormalities.
AB  - Hutchinson-Gilford progeria syndrome (HGPS) is a typical presenile disorder, with
      mutation in the LMNA gene. Besides HGPS, mutations in LMNA gene have also been
      reported in atypical progeroid syndrome (APS). The objective of the study was to
      investigate the phenotype and molecular basis of APS in a Chinese family. LMNA
      gene mutations were also reviewed to identify the phenotypic and pathogenic
      differences among APS. Two siblings in a non-consanguineous Chinese family with
      atypical progeria were reported. The clinical features were observed, including
      presenile manifestations such as bird-like facial appearance, generalized
      lipodystrophy involving the extremities and mottled hyperpigmentation on the
      trunk and extremities. A heterozygous mutation c.11C>G (p.Pro4Arg) of the LMNA
      gene was detected in the two patients. 28 different variants of the LMNA gene
      have been reported in APS families, spreading over almost all the 12 exons of the
      LMNA gene with some hot-spot regions. This is the first detailed description of
      an APS family without metabolism abnormalities. APS patients share most of the
      clinical features, but there may be some distinct features in different ethnic
      groups.

PMID- 24861649
TI  - Pre-hysterectomy assessment of immediate tubal occlusion with the third
      generation ESSURE insert (ESS505).
AB  - STUDY OBJECTIVE: To assess the ability of a new iteration of the ESSURE insert
      (ESS505) to achieve short-term fallopian tube occlusion. DESIGN: Prospective,
      single center, interventional cohort (Canadian Task Force classification II-1).
      SETTING: Tertiary care hospital. PATIENTS: Women scheduled to undergo
      hysterectomy. INTERVENTION: Patients underwent placement of the ESS505 in the
      right fallopian tube and ESS305 (the commercially approved previous version of
      the device) in the left fallopian tube at 30 (n = 10), 60 (n = 10), or 90 (n =
      10) days before a planned hysterectomy. Tubal occlusion was assessed via
      hysterosalpingography (HSG) both at the time of placement and just before
      hysterectomy. Ultrasound was used to evaluate acute device placement.
      MEASUREMENTS AND MAIN RESULTS: Thirty-five women (mean age, 39.7 years) were
      enrolled from July 2012 to January 2013, and 30 underwent both ESSURE placement
      and scheduled hysterectomy. Mean (SD) placement time for the ESS305 and ESS505
      devices was 1.4 (0.65) minutes and 1.3 (0.42) minutes, respectively (p = .36). At
      1 hour after ESS505 placement, 29 of 30 tubes (97%) exhibited complete occlusion
      at HSG, compared with only 4 of 30 tubes (13%) after ESS305 placement (p < .001
      for difference in occlusion rates). At hysterectomy, the tubal occlusion rate was
      high in both groups: 97% for ESS505 and 100% for ESS305 tubes. High occlusion
      rates were observed in each of the 3 duration groups (30, 60, and 90 days). Five
      women experienced only minor adverse effects. CONCLUSION: ESS505, a modification
      to the commercially available ESS305 designed to cause immediate tubal occlusion,
      demonstrated a high rate of both immediate-term and intermediate-term tubal
      occlusion. Early tubal occlusion may obviate the need for interim alternative
      contraceptive methods after ESSURE placement.

PMID- 24861650
TI  - The preoperative evaluation and surgical treatment of epilepsy.
AB  - BACKGROUND: One-third of all patients with epilepsy have persistent seizures
      despite medical treatment. If the origin of the seizures can be localized to a
      particular site in the brain, epilepsy surgery is a treatment option that
      addresses the cause of the problem. METHOD: The presurgical assessment and
      surgical treatment of epilepsy are discussed on the basis of a selective
      literature review and the authors' clinical experience. RESULTS: Recent studies
      give further evidence that surgical treatment is superior to continued medical
      treatment for patients with seizures of focal origin that persist despite
      treatment with two antiepileptic drugs. Modern imaging and electrophysiological
      techniques enable the demonstration of subtle structural and functional changes
      of the cerebral cortex as a basis for individually tailored surgical resection.
      60-80% of surgically treated patients become seizure-free. According to recent
      reviews, epilepsy surgery is associated with a permanent morbidity of 6% and with
      a mortality well under 1%; these figures are in the typical range for
      neurosurgical procedures. In the authors' series, 2% of patients had permanent
      complications, and the death rate was less than 0.1%. CONCLUSION: Advances in
      presurgical assessment and the broad range of available surgical techniques have
      widened the applicability of surgical treatment for children and adults with
      medically refractory epilepsy. Patients should be referred early in the course of
      their disease to an epilepsy center for evaluation of the surgical options.

PMID- 24861651
TI  - Results of a workplace health campaign: what can be achieved?
AB  - BACKGROUND: Effective health promotion in the workplace is now essential because
      of the rising health-related costs for businesses, the increasing pressure
      arising from international competition, prolonged working lives, and the aging of
      the work force. The basic problem of prevention campaigns is that the target
      groups are too rarely reached and sustainable benefits too rarely achieved. In
      2011, we carried out a broad-based health and fitness campaign to assess how many
      personnel could be motivated to participate in a model study under nearly ideal
      conditions. METHOD: 1010 personnel were given the opportunity to participate in
      various kinds of sports, undergo sports-medicine examinations, attend monthly
      expert lectures, and benefit from nutritional offerings and Intranet information
      during work hours. Pseudonymized questionnaires were used to classify the
      participants according to their exercise behavior as non-active, not very active,
      and very active. The participants' subjective responses (regarding, e.g., health,
      exercise, nutrition, and the factors that motivated them to participate in sports
      or discouraged them from doing so) were recorded, as were their objective data
      (measures of body size and strength). The duration of the study was one year.
      RESULTS: 490 of the 1010 personnel (48.5%, among whom 27.2% were nonactive, 44.1%
      not very active, and 28.7% very active) participated in the initial questionnaire
      and testing. By the end of the study, this figure had dropped to 17.8%;
      diminished participation affected all three groups to a comparable extent. A
      comparison of dropouts and non-dropouts revealed that older age was a stable
      predictor for drop-out (bivariate odds ratio [OR] 1.028, p = 0.006; multivariate
      OR 1.049, p = 0.009). The study participants reported beneficial effects on their
      health and health awareness, performance ability, psychological balance, stress
      perception, exercise and dietary behavior. CONCLUSION: Even under optimal
      conditions and with high use of staff resources, this model study (which cannot
      be universally implemented) did not lead to comprehensive and sustained personnel
      participation. This finding suggests that the currently available prevention
      instruments are insufficient for the effective and cost-efficient promotion of
      health and fitness in the workplace.

PMID- 24861652
TI  - School headache.

PMID- 24861653
TI  - Functional block.

PMID- 24861654
TI  - Considering the eyes.

PMID- 24861655
TI  - In reply.

PMID- 24861656
TI  - Strong empathy a must.

PMID- 24861657
TI  - A poor soloist in most cases.

PMID- 24861658
TI  - In reply.

PMID- 24861660
TI  - Normal dopamine transporter imaging does not exclude multiple system atrophy.

PMID- 24861659
TI  - Factors influencing wound healing complications after wide excision of injection
      site sarcomas of the trunk of cats.
AB  - OBJECTIVE: Wide surgery is the mainstay of the multimodal treatment of injection
      site sarcomas (ISS) in cats. The aim of the study was to analyze potential
      factors influencing the development of wound healing complications (WHC) in cats
      undergoing wide excision of ISS. STUDY DESIGN: Retrospective case series.
      ANIMALS: Forty-nine cats with ISS located on the trunk underwent wide excision
      after contrast-enhanced computed tomography planning. METHODS: The prognostic
      effect of covariates (sex, age, weight, body condition score (BCS), site,
      clinical dimension (CD), computed tomographic dimension (CTD), histotype,
      duration of surgery, surgical margin status, local anesthesia) on total, major
      and minor WHC was evaluated by univariate and bivariate analysis. Cox model was
      used for total WHC and Fine and Gray model was used for major and minor WHC. The
      relationship between duration of surgery and clinical and imaging variables was
      evaluated. RESULTS: The main factor associated to the risk of total and major WHC
      was surgical time. Based on univariate analysis, pattern of reconstruction, CDT,
      CD, weight, and BCS were significant prognostic factors for major WHC, but this
      was not confirmed when adjusted for other clinical variables in bivariate
      analysis. The duration of surgery was influenced by excision pattern and tumor
      CTD width. CONCLUSIONS: An increased duration of surgery as the consequence of
      complex surgical procedures represented the best predictor for the development of
      WHC.

PMID- 24861661
TI  - Rasagiline effect on bladder disturbances in early mild Parkinson's disease
      patients.

PMID- 24861662
TI  - Percutaneous irreversible electroporation for the treatment of colorectal cancer
      liver metastases with a proposal for a new response evaluation system.
AB  - PURPOSE: To describe an initial experience with irreversible electroporation
      (IRE) in patients with colorectal liver metastasis (CLM). MATERIALS AND METHODS:
      A retrospective analysis of patients undergoing IRE for the management of CLM was
      performed. Procedures were done percutaneously under general anesthesia. Patients
      were then followed for adverse events, tumor response, and survival. RESULTS:
      Between March 2010 and February 2013, 29 patients underwent percutaneous ablation
      of 58 tumors in 36 IRE sessions. Most patients (89%) had an absolute or relative
      contraindication to thermal ablation. The median age was 62 years, and the median
      time from diagnosis to IRE was 28 months. The median number of lesions treated
      per patient was two, and the median tumor size was 2.7 cm. Patients had received
      previous chemotherapy regimens (range, 1-5 per patient). A new Metabolic Imaging
      And Marker Integration response evaluation criteria was used for response
      assessment, and was a predictor of progression-free and overall survival. The 2
      year progression-free survival rate was 18% (95% confidence interval, 0%-35%),
      and the 2-year overall survival rate was 62% (95% confidence interval, 37%-87%).
      Complications included arrhythmias (n = 1) and postprocedure pain (n = 1). Both
      patients recovered without sequelae. CONCLUSIONS: Percutaneous IRE of CLM is
      feasible and safe. A new response evaluation system for colorectal cancer appears
      to be prognostic.

PMID- 24861663
TI  - Pharmacokinetics and antitumor efficacy of chemoembolization using 40 um
      irinotecan-loaded microspheres in a rabbit liver tumor model.
AB  - PURPOSE: To evaluate the pharmacokinetics and antitumor efficacy of 40 MUm
      irinotecan-loaded drug-eluting microspheres (Embozene TANDEM Microspheres;
      CeloNova BioSciences, Inc, San Antonio, Texas) (TANDEM-IRI). MATERIALS AND
      METHODS: The following three groups included eight VX2 rabbits each: group 1,
      full-loaded (50 mg irinotecan/1 mL TANDEM)/high-dose injection (1 mg
      irinotecan/kg); group 2, full-loaded (50 mg irinotecan/1 mL TANDEM)/low-dose
      injection (0.5 mg irinotecan/kg); and group 3, half-loaded (25 mg irinotecan/1 mL
      TANDEM)/low-dose injection (0.5 mg irinotecan/kg). Irinotecan and SN-38 in the
      plasma and tumors were measured within 72 hours. Histologic examinations were
      conducted on days 1, 3, and 7. RESULTS: Serum irinotecan levels remained near the
      maximum concentration for 180 minutes after transarterial chemoembolization; in
      group 1, levels were 351.4 ng/mL at 30 minutes, 329.0 ng/mL at 60 minutes, and
      333.5 ng/mL at 180 minutes. The area under the curve for 0-24 hours of irinotecan
      in group 1 was approximately two times higher than the same value in groups 2 and
      3. High irinotecan and SN-38 concentrations in the tumors were measured at 24
      hours and 72 hours. After transarterial chemoembolization, levels of liver
      enzymes aspartate aminotransferase and alkaline phosphatase were significantly
      higher in group 1 compared with groups 2 and 3. Histologic findings showed
      microspheres had deeply penetrated into tumors. Significantly higher tumor
      necrosis ratios were observed in groups 1 (86.6%-90.0%) and 3 (90.0%-100%)
      compared with group 2 (63.3%-70%) (P = .031 and P = .016). CONCLUSIONS: Slow drug
      release with high drug concentration in tumors can be provided with 40 MUm TANDEM
      IRI. When complete arterial embolization is performed, the dose of irinotecan
      loaded on 40 MUm TANDEM microspheres can be reduced while maintaining efficacy.

PMID- 24861664
TI  - Cost effectiveness of radioembolization compared with conventional transarterial
      chemoembolization for treatment of hepatocellular carcinoma.
AB  - PURPOSE: To assess cost effectiveness of radioembolization versus conventional
      transarterial chemoembolization. MATERIALS AND METHODS: The cost of
      radioembolization versus conventional transarterial chemoembolization was
      determined based on Medicare reimbursements. Three patient subgroups were defined
      based on the Barcelona Clinic Liver Cancer (BCLC) classification system (A, B, or
      C). Efficacy and safety outcomes after each procedure were obtained from the
      literature. A Monte Carlo case-based simulation was designed for 60 months in 250
      patients in each subgroup. Survival was calculated based on average survival from
      the literature and the Monte Carlo model. The primary outcome was the cost
      effectiveness of radioembolization over transarterial chemoembolization by
      considering calculated survival. RESULTS: The costs approached $17,000 for
      transarterial chemoembolization versus $31,000 or $48,000 for unilobar or bilobar
      radioembolization, respectively. Based on the simulation, median estimated
      survival was greater with transarterial chemoembolization than radioembolization
      in BCLC-A and BCLC-B subgroups (40 months vs 30 months and 23 months vs 16
      months, respectively, P = .001). However, in the BCLC-C subgroup, survival was
      greater with radioembolization than transarterial chemoembolization (13 months vs
      17 months, P = .001). The incremental cost-effectiveness ratio of
      radioembolization over transarterial chemoembolization in the BCLC-C subgroup was
      $360 per month. The results were dependent on bilobar versus unilobar
      radioembolization and the total number of radioembolization procedures.
      CONCLUSIONS: The model suggests radioembolization costs may be justified for
      patients with BCLC-C disease, whereas radioembolization may not be cost effective
      in patients with BCLC-A disease; however, many patients with BCLC-C disease have
      extensive disease precluding locoregional therapies. Secondary considerations may
      determine treatment choice in more borderline patients (BCLC-B disease) because
      there is no persistent survival benefit with radioembolization.

PMID- 24861665
TI  - The refractive index and electronic gap of water and ice increase with increasing
      pressure.
AB  - Determining the electronic and dielectric properties of water at high pressure
      and temperature is an essential prerequisite to understand the physical and
      chemical properties of aqueous environments under supercritical conditions, for
      example, in the Earth interior. However, optical measurements of compressed ice
      and water remain challenging, and it has been common practice to assume that
      their band gap is inversely correlated with the measured refractive index,
      consistent with observations reported for hundreds of materials. Here we report
      ab initio molecular dynamics and electronic structure calculations showing that
      both the refractive index and the electronic gap of water and ice increase with
      increasing pressure, at least up to 30 GPa. Subtle electronic effects, related to
      the nature of interband transitions and band edge localization under pressure,
      are responsible for this apparently anomalous behaviour.

PMID- 24861667
TI  - Synthesis of 1,4,7,10-tetra-azacyclododecan-1,4,7,10-tetra-azidoethylacetic acid
      (DOTAZA) and related "clickable" DOTA derivatives.
AB  - Herein, we report the synthesis of two enantiomeric DOTAZA esters and a related
      DOT3AZA ester. These compounds are tunable analogues of the well-known chelator
      DOTA and can be easily functionalized through click chemistry of the side-chain
      azide groups. Like DOTA, DOTAZA forms complexes with various di- and trivalent
      metals, as demonstrated in the synthesis and structural analysis of Cu?DOTAZA and
      the preparation of Gd?DOTAZA. 

PMID- 24861666
TI  - N-Acetylcysteine does not protect behavioral and biochemical toxicological effect
      after acute exposure of diphenyl ditelluride.
AB  - Diphenyl ditelluride (PhTe)2 is a versatile molecule used in the organic
      synthesis and it is a potential prototype for the development of novel
      biologically active molecules. The mechanism(s) involved in (PhTe)2 toxicity
      is(are) elusive, but thiol oxidation of critical proteins are important targets.
      Consequently, the possible remedy of its toxicity by thiol-containing compounds
      is of experimental and clinical interest. The present study aimed to investigate
      putative mechanisms underlying the toxicity of (PhTe)2 in vivo. We assessed
      behavioral and oxidative stress parameters in mice, including the modulation of
      antioxidant enzymatic defense systems. In order to mitigate such toxicity, N
      acetylcysteine (NAC) was administered before (3 d) and simultaneously with
      (PhTe)2 (7 d). Mice were separated into six groups receiving daily injections of
      (1) TFK (2.5 ml/kg, intraperitonealy (i.p.)) plus canola oil (10 ml/kg,
      subcutaneously (s.c.)), (2) NAC (100 mg/kg, i.p.) plus canola oil s.c., (3) TFK
      i.p. plus (PhTe)2 (10 umol/kg, s.c.), (4) TFK i.p. plus (PhTe)2 (50 umol/kg,
      s.c.), (5) NAC plus (PhTe)2 (10 umol/kg, s.c.), and (6) NAC plus (PhTe)2 (50
      umol/kg, s.c.). (PhTe)2 treatment started on the fourth day of treatment with
      NAC. Results demonstrated that (PhTe)2 induced behavioral alterations and
      inhibited important selenoenzymes (thioredoxin reductase and glutathione
      peroxidase). Treatments produced no or minor effects on the activities of
      antioxidant enzymes catalase and glutathione reductase. Contrary to expected, NAC
      co-administration did not protect against the deleterious effects of (PhTe)2.
      Other low-molecular-thiol containing molecules should be investigated to
      determine whether or not they can be effective against ditellurides.

PMID- 24861669
TI  - Three roles for the fluoride ion in palladium-catalyzed Hiyama reactions:
      transmetalation of [ArPdFL2] by Ar'Si(OR)3.
AB  - From the kinetic data on the transmetalation/reductive elimination in fluoride
      promoted Hiyama reactions, obtained using electrochemical techniques, it has been
      established that fluoride ions play three roles. F(-) reacts with trans
      [ArPdBrL2] (L=PPh3) to form trans-[ArPdFL2], which reacts with Ar'Si(OMe)3 in the
      rate-determining transmetalation, whereas trans-[ArPdBrL2] does not react with
      Ar'Si(OMe)3. F(-) reacts with Ar'Si(OMe)3 to deliver the unreactive silicate
      Ar'SiF(OMe)3(-), thus leading to two antagonistic kinetic effects. In addition,
      F(-) catalyzes the reductive elimination from intermediate trans-[ArPdAr'L2].

PMID- 24861670
TI  - Photocatalytic conversion of CO(2) into renewable hydrocarbon fuels: state-of-the
      art accomplishment, challenges, and prospects.
AB  - Photocatalytic reduction of CO2 into hydrocarbon fuels, an artificial
      photosynthesis, is based on the simulation of natural photosynthesis in green
      plants, whereby O2 and carbohydrates are produced from H2 O and CO2 using
      sunlight as an energy source. It couples the reductive half-reaction of CO2
      fixation with a matched oxidative half-reaction such as water oxidation, to
      achieve a carbon neutral cycle, which is like killing two birds with one stone in
      terms of saving the environment and supplying future energy. The present review
      provides an overview and highlights recent state-of-the-art accomplishments of
      overcoming the drawback of low photoconversion efficiency and selectivity through
      the design of highly active photocatalysts from the point of adsorption of
      reactants, charge separation and transport, light harvesting, and CO2 activation.
      It specifically includes: i) band-structure engineering, ii)
      nanostructuralization, iii) surface oxygen vacancy engineering, iv) macro-/meso
      /microporous structuralization, v) exposed facet engineering, vi) co-catalysts,
      vii) the development of a Z-scheme system. The challenges and prospects for
      future development of this field are also present. 

PMID- 24861668
TI  - Vaccines against human diarrheal pathogens: current status and perspectives.
AB  - Worldwide, nearly 1.7 billion people per year contract diarrheal infectious
      diseases (DID) and almost 760 000 of infections are fatal. DID are a major
      problem in developing countries where poor sanitation prevails and food and water
      may become contaminated by fecal shedding. Diarrhea is caused by pathogens such
      as bacteria, protozoans and viruses. Important diarrheal pathogens are Vibrio
      cholerae, Shigella spp. and rotavirus, which can be prevented with vaccines for
      several years. The focus of this review is on currently available vaccines
      against these three pathogens, and on development of new vaccines. Currently,
      various types of vaccines based on traditional (killed, live attenuated, toxoid
      or conjugate vaccines) and reverse vaccinology (DNA/mRNA, vector, recombinant
      subunit, plant vaccines) are in development or already available. Development of
      new vaccines demands high levels of knowledge, experience, budget, and time, yet
      promising new vaccines often fail in preclinical and clinical studies. Efficacy
      of vaccination also depends on the route of delivery, and mucosal immunization in
      particular is of special interest for preventing DID. Furthermore, adjuvants,
      delivery systems and other vaccine components are essential for an adequate
      immune response. These aspects will be discussed in relation to the improvement
      of existing and development of new vaccines against DID.

PMID- 24861671
TI  - Antenatal counselling for congenital anomaly tests: an exploratory video
      observational study about client-midwife communication.
AB  - OBJECTIVE: antenatal counselling for congenital anomaly tests is conceptualised
      as having both Health Education (HE) and Decision-Making Support (DMS) functions.
      Building and maintaining a client-midwife relation (CMR) is seen as a necessary
      condition for enabling these two counselling functions. However, little is known
      about how these functions are fulfilled in daily practice. This study aims to
      describe the relative expression of the antenatal counselling functions; to
      describe the ratio of client versus midwife conversational contribution and to
      get insight into clients' characteristics, which are associated with midwives'
      expressions of the functions of antenatal counselling. DESIGN: exploratory video
      observational study. PARTICIPANTS AND SETTING: 269 videotaped antenatal
      counselling sessions for congenital anomaly tests provided by 20 midwives within
      six Dutch practices. MEASUREMENTS: we used an adapted version of the Roter
      Interaction Analysis System to code the client-midwife communication. Multilevel
      linear regression analyses were used to analyse associations between clients'
      characteristics and midwives' expressions of antenatal counselling in practice.
      FINDINGS: most utterances made during counselling were coded as HE (41%); a
      quarter as DMS (23%) and 36% as CMR. Midwives contributed the most to the HE
      compared to clients or their partners (91% versus 9%) and less to the DMS
      function of counselling (61% versus 39%). Multilevel analyses showed an
      independent association between parity and shorter duration of antenatal
      counselling; (beta=-3.01; p<0.001). The amount of utterances concerning HE and
      DMS during counselling of multipara was less compared to nulliparous. KEY
      CONCLUSIONS: antenatal counselling for congenital anomaly tests by midwives is
      focused on giving HE compared to DMS. The relatively low contribution of clients
      during DMS might indicate poor DMS given by midwives. Counselling of multipara
      was significantly shorter than counselling of nulliparous; multiparae received
      less HE as well as DMS compared to nulliparous women. IMPLICATIONS FOR PRACTICE:
      our findings should encourage midwives to reflect on the process of antenatal
      counselling they offer with regards to the way they address the three antenatal
      counselling functions during counselling of nulliparous women compared to
      multiparae.

PMID- 24861672
TI  - Women's views about maternity care: how do women conceptualise the process of
      continuity?
AB  - OBJECTIVE: to gain an understanding of how women conceptualise continuity of
      maternity care. DESIGN: a qualitative study involving in-depth semi-structured
      interviews and thematic analysis. SETTING: a range of urban and rural public
      hospitals in New South Wales, Australia. PARTICIPANTS: 53 women aged 18-44 years
      (median age 27 years) receiving maternity care in 2011-2012. FINDINGS: responses
      from women suggested five concepts of continuity: continuity of staff, continuity
      of relationship, continuity of information, continuity across pregnancies and
      continuity across locations. These concepts of continuity differed by parity and
      location. CONCLUSION AND IMPLICATIONS FOR PRACTICE: continuity of maternity care
      has a variety of meanings to women. If health care providers are to commit to
      providing woman-centred maternity care it is important to recognise the diversity
      of women's experiences, and ensure that systems of care are flexible and
      appropriate to women's circumstances and needs.

PMID- 24861674
TI  - Translation and validation of the German version of the Mother-Generated Index
      and its application during the postnatal period.
AB  - OBJECTIVE: the Mother-Generated Index (MGI) is a validated tool to assess
      postnatal quality of life. It is usually administered several weeks or months
      after birth and correlates with indices of post partum mood states and physical
      complaints. The instrument had not been translated into German before or
      validated for use among German-speaking women, nor have the results of the tool
      been assessed specifically for the administration directly after birth. This
      paper aims to describe the systematic translation process of the MGI into German
      and to assess the convergent validity of the German version of the instrument
      directly after birth and seven weeks post partum. DESIGN: prospective two-stage
      survey. SETTING: two rural hospitals in the south of Germany and in the north of
      Switzerland. PARTICIPANTS: all women giving birth between 1st October and 15th
      December 2012 with sufficient knowledge of German and whose babies were not
      referred to a neonatal care unit; 226 women were eligible to participate.
      MEASUREMENT INSTRUMENTS: two questionnaires including questions relating to socio
      demographic factors and perinatal care, and incorporating the MGI, the Hospital
      Anxiety and Depression Scale (HADS) and the Postnatal Morbidity Index (PMI). All
      instruments were subjected to forward and back translation and pilot-tested; the
      first questionnaire was then administered in the first two days after birth and
      the second six weeks post partum. Parametric and non-parametric tests were
      computed using SPSS. FINDINGS: 129 surveys were returned an average of three days
      after birth and 83 after seven weeks. Higher postnatal quality of life showed a
      significant correlation with a lower anxiety and depression score (p<0.01), fewer
      maternal physical complaints (p<0.05) and more favourable baby adjective scores
      (p<0.05) after birth. Significant associations were found between MGI scores and
      sufficient help (p=0.03) as well as ability to cope at home (p<0.01). MGI scores
      three days and seven weeks after birth correlated highly significantly and
      positively (p<0.001). KEY CONCLUSIONS: convergent validity of the MGI with the
      HADS and the PMI suggests that the German version of the MGI is a valid indicator
      of physical and emotional post partum well-being. IMPLICATION FOR PRACTICE: the
      German version of the MGI can be used in the post partum period to identify women
      whose quality of life is impaired during the first days after birth, in order to
      initiate extended midwifery care and referral if necessary.

PMID- 24861673
TI  - Physical activity, sedentary behaviour and fetal macrosomia in uncomplicated
      pregnancies: a prospective cohort study.
AB  - OBJECTIVE: to explore maternal energy balance, incorporating free living physical
      activity and sedentary behaviour, in uncomplicated pregnancies at risk of
      macrosomia. METHODS: a parallel-group cross-sectional analysis was conducted in
      healthy pregnant women predicted to deliver infants weighing >= 4000 g (study
      group) or < 4000 g (control group). Women were recruited in a 1:1 ratio from
      antenatal clinics in Northern Ireland. Women wore a SenseWear((r)) Body Media
      Pro3 physical activity armband and completed a food diary for four consecutive
      days in the third trimester. Physical activity was measured in Metabolic
      Equivalent of Tasks (METs) where 1 MET = 1 kcal per kilogram of body weight per
      hour. Analysis of covariance (ANCOVA) was employed using the General Linear Model
      to adjust for potential confounders. FINDINGS: of the 112 women recruited, 100
      complete datasets were available for analysis. There was no significant
      difference in energy balance between the two groups. Intensity of free living
      physical activity (average METs) of women predicted to deliver macrosomic infants
      (n = 50) was significantly lower than that of women in the control group (n = 50)
      (1.3 (0.2) METs (mean, standard deviation) versus 1.2 (0.2) METs; difference in
      means -0.1 METs (95% confidence interval: -0.19, -0.01); p = 0.021). Women
      predicted to deliver macrosomic infants also spent significantly more time in
      sedentary behaviour (<= 1 MET) than the control group (16.1 (2.8) hours versus
      13.8 (4.3) hours; 2.0 hours (0.3, 3.7), p = 0.020). KEY CONCLUSIONS AND
      IMPLICATIONS FOR PRACTICE: although there was no association between predicted
      fetal macrosomia and energy balance, those women predicted to deliver a
      macrosomic infant exhibited increased sedentary behaviour and reduced physical
      activity in the third trimester of pregnancy. Professionals caring for women
      during pregnancy have an important role in promoting and supporting more active
      lifestyles amongst women who are predicted to deliver a macrosomic infant given
      the known associated risks.

PMID- 24861676
TI  - Interventricular septal rupture after transcatheter aortic valve implantation:
      surgical and perioperative management.
AB  - Transcatheter aortic valve implantation (TAVI) is associated with various
      complications, usually related to valve positioning or prosthesis delivery. We
      report the rare complication of an iatrogenic ventricular septal defect,
      secondary to aortic annulus disruption after TAVI-transfemoral procedure,
      generating a significant left-to-right shunt and cardiac failure. Open surgical
      procedures under cardiopulmonary bypass remain the best option for this lethal
      complication.

PMID- 24861675
TI  - Invasive group A Streptococcus infections associated with liposuction surgery at
      outpatient facilities not subject to state or federal regulation.
AB  - IMPORTANCE: Liposuction is one of the most common cosmetic surgery procedures in
      the United States. Tumescent liposuction, in which crystalloid fluids, lidocaine,
      and epinephrine are infused subcutaneously before cannula-assisted aspiration of
      fat, can be performed without intravenous or general anesthesia, often at
      outpatient facilities. However, some of these facilities are not subject to state
      or federal regulation and may not adhere to appropriate infection control
      practices. OBJECTIVE: To describe an outbreak of severe group A Streptococcus
      (GAS) infections among persons undergoing tumescent liposuction at 2 outpatient
      cosmetic surgery facilities not subject to state or federal regulation. DESIGN:
      Outbreak investigation (including cohort analysis of at-risk patients),
      interviews using a standardized questionnaire, medical record review, facility
      assessment, and laboratory analysis of GAS isolates. SETTING AND PARTICIPANTS:
      Patients undergoing liposuction at 2 outpatient facilities, one in Maryland and
      the other in Pennsylvania, between July 1 and September 14, 2012. MAIN OUTCOMES
      AND MEASURES: Confirmed invasive GAS infections (isolation of GAS from a normally
      sterile site or wound of a patient with necrotizing fasciitis or streptococcal
      toxic shock syndrome), suspected GAS infections (inflamed surgical site and
      either purulent discharge or fever and chills in a patient with no alternative
      diagnosis), postsurgical symptoms and patient-reported experiences related to his
      or her procedure, and emm types, T-antigen types, and antimicrobial
      susceptibility of GAS isolates. RESULTS: We identified 4 confirmed cases and 9
      suspected cases, including 1 death (overall attack rate, 20% [13 of 66]). One
      instance of likely secondary GAS transmission to a household member occurred. All
      confirmed case patients had necrotizing fasciitis and had undergone surgical
      debridement. Procedures linked to illness were performed by a single surgical
      team that traveled between the 2 locations; 2 team members (1 of whom reported
      recent cellulitis) were colonized with a GAS strain that was indistinguishable by
      laboratory analysis of the isolates from the case patients. Facility assessments
      and patient reports indicated substandard infection control, including errors in
      equipment sterilization and infection prevention training. CONCLUSIONS AND
      RELEVANCE: This outbreak of severe GAS infections was likely caused by
      transmission from colonized health care workers to patients during liposuction
      procedures. Additional oversight of outpatient cosmetic surgery facilities is
      needed to assure that they maintain appropriate infection control practices and
      other patient protections.

PMID- 24861677
TI  - C9ORF72 repeat-associated non-ATG-translated polypeptides are distributed
      independently of TDP-43 in a Japanese patient with c9ALS.

PMID- 24861678
TI  - Type I flavohemoglobin of mycobacterium smegmatis is a functional nitric oxide
      dioxygenase.
AB  - Two flavohemoglobins, type I and type II, displaying distinct structural features
      and cofactor binding sites coexist in Mycobacterium smegmatis; however, none of
      these flavohemeproteins are characterized so far. We have cloned and expressed
      type I flavohemoglobin (FHb1) of Mycobacterium smegmatis, encoded by MSMEG_1336,
      and characterized its spectral and functional properties. FHb1 exists as a
      monomer and displays spectral and functional characteristics similar to HMP of E.
      coli. Specific NO dioxygenase (NOD) activity of FHb1 was estimated to be 63.5
      nmol heme(-1) sec(-1) , which was nearly eightfold higher than the HbN of M.
      tuberculosis and matched closely to the HMP of E. coli on the basis of cellular
      heme content. FHb1 preferred NADH for the NO dioxygenation and exhibited rapid
      reduction of flavin adenine dinucleotide and heme iron using NADH as electron
      donor. Level of FHb1 transcript increased significantly in M. smegmatis in the
      presence of acidified nitrite, and a nitric oxide-responsive transcriptional
      regulator of Rrf2 family exists together with the FHb1 under the same operon.
      These results suggested that FHb1 of M. smegmatis is a functional NOD and may be
      involved in the stress management of its host toward nitric oxide and nitrosative
      stress.

PMID- 24861679
TI  - [Quantitative imaging in uro-oncology].
AB  - INTRODUCTION: Imaging currently performed in uro-oncology could provide useful
      information. The use of all this information could help to better understand
      tumor growth and response to treatment. Therefore, it seems interesting to review
      the knowledge, to describe the main techniques currently available in many
      centers or in process and to clarify their results. MATERIALS AND METHODS: A
      systematic literature review was conducted in the PubMed database to identify all
      imaging techniques performed for therapeutic evaluation in uro-oncology. The
      keywords used were: cancer, kidney, bladder, prostate, urology biomarkers,
      imaging, ultrasound, CT-scan, MRI, PET-CT, RECIST, BOLD, ASL, gold DWI Diffusion,
      contrast, F-miso. The first publications identified were analyzed to search
      unidentified studies by the selected keywords. RESULTS: From simple to more
      complex morphology data from functional imaging (PET, MRI), data obtained from
      imaging helps to better understand tumor growth and response to treatment.
      Although optimizations are coming, all the techniques reported are available in
      many centers or going to be. CONCLUSION: The imaging evaluation in onco-urology
      can bring a large amount of information. Integrating to research protocols is now
      essential to sustain this activity.

PMID- 24861680
TI  - [Painful ejaculation].
AB  - OBJECTIVE: To clarify definition, epidemiology, diagnosis, evaluation, etiologies
      and treatment of painful ejaculation (PE). MATERIAL AND METHODS: Review of the
      literature performed by searching the Medline database using keywords
      ejaculation, orgasm, pain, pelvic pain, sexual behavior. RESULTS: PE is a
      pelviperineal pain caused by ejaculation or orgasm. Its prevalence rate is
      between 1 and 4% amongst the general population. Mainly located in the penis,
      pain usually lasts less than 5 minutes. Assessment is clinical and there is no
      level of evidence about the strategy of complementary investigations. Benign
      prostatic hyperplasia, chronic pelvic pain syndrome, radical prostatectomy,
      prostate brachytherapy and some antidepressant medications are the best estimated
      etiologies found in the literature. A link between urogenital infections and PE
      is likely but not clearly established. Alpha-blockers had good therapeutic
      results in few low level of evidence studies. CONCLUSION: The assessment of PE is
      not clearly defined. Some etiologies are known but PE may be a functionnal pain.
      Only high level of evidence studies would validate the use of the alpha-blockers
      as an efficient therapeutic option.

PMID- 24861681
TI  - [Initial assessment of male non-neurogenic incontinence: systematic review of the
      literature by the LUTS committee of the French Urological Association].
AB  - PURPOSE: To perform an update on the initial evaluation of male urinary
      incontinence (MUI). METHOD: A systematic review was conducted using
      Pubmed/Medline from 1995 to 2013. RESULTS: Definition of MUI and its prevalence
      is variable according its definition and the population. Tools for its evaluation
      have been mainly studied in female population or only in patients with UI after
      radical prostatectomy. Objectives of the initial evaluation are to assess the
      type of incontinence, to evaluate its severity and the bother associated, and
      define the choice of treatment. Medical history, clinical assessment, and urine
      analysis are the first steps of the evaluation. Bladder diary, questionnaires and
      pad test can be useful to evaluate MUI. Post-void residual volume assessment is
      necessary if lower urinary tract symptoms are associated. Imaging is not
      routinely used in MUI. A specialist referral and further investigations such as
      urethrocystoscopy and urodynamics should be considered in case of invasive
      treatment, recurrent incontinence and specific situations. CONCLUSIONS: Initial
      assessment of MUI should be sequential with systematic investigations and
      optional ones.

PMID- 24861682
TI  - [Determination of the 120-day post prostatic biopsy mortality rate].
AB  - OBJECTIVE: Concerning death-rates were reported following prostate biopsy but the
      lack of contexts in which event occurred makes it difficult to take any position.
      Therefore, we aimed to determine the 120-day post-biopsy mortality rate. MATERIAL
      AND METHODS: Between 2000 and 2011, 8804 men underwent prostate biopsy in the
      hospice civils de Lyon. We studied retrospectively, the mortality rate after each
      of the 11,816 procedures. Biopsies imputability was assessed by examining all
      medical records. Dates of death were extracted from our local patient management
      database, which is updated trimestrially with death notifications from the French
      National Institute for Statistics and Economic Studies. RESULTS: In our study 42
      deaths occurred within 120days after 11,816 prostate biopsies (0.36%). Of the 42
      records: 9 were lost to follow-up, 3 had no identifiable cause of death, 28 had
      an intercurrent event ruling out prostate biopsy as a cause of death. Only 2
      deaths could be linked to biopsy. CONCLUSIONS: We reported at most 2 deaths
      possibly related to prostate biopsy over 11,816 procedures (0.02%). We confirmed
      the fact that prostate biopsies can be lethal but this rare outcome should not be
      considered as an argument against prostate screening given the circumstances in
      which it occurs. LEVEL OF EVIDENCE: 5.

PMID- 24861683
TI  - [Existence of pattern 5 on radical prostatectomy: poor prognostic factor
      associated with a lower biochemical recurrence-free survival].
AB  - OBJECTIVES: To analyze the impact of the existence of Gleason grade 5 on the
      adverse pathology and biochemical recurrence-free survival of patients. PATIENTS:
      Three hundred and seventy-two prostatectomies were performed between 1999 and
      2011 in our institution for localised prostate adenocarcinoma. We examined the
      existence of grade 5 of the specimen to determine the reliability of prostate
      biopsies in the diagnosis of grade 5 and the association of grade 5 with other
      histoprognostic factors. Biochemical recurrence-free survival was analyzed
      according to the presence of grade 5 in the final specimen. RESULTS: In total,
      all histological data and biochemical recurrence-free survival were available for
      321 patients who were included in the study. Sixty-eight had Gleason grade 5
      (majority or third minority pattern) on the specimen while 253 had not. Grade 5,
      rarely diagnosed on biopsy (sensitivity=26.47 %) was correlated independently
      with the extracapsular extension (OR=2.1; CI 95 [1.1-3.9]), the seminal vesicle
      invasion (OR=3.8; CI 95 [1.7-8.7]) and positive surgical margins (OR=2.0; CI 95
      [1.1-3.6]). Overall survival was similar in both groups but the biochemical
      recurrence-free survival was statistically lower in the presence of grade 5
      (HR=3.7; CI 95 [1.8-7.6]). Biochemical recurrence-free survival was not different
      than grade 5 is predominant or third minority pattern (HR=1.01; CI 95 [0.3-2.8]).
      On multivariate analysis, grade 5 was an independent risk factor for biochemical
      recurrence (P=0.005) as well as seminal vesicle invasion (P=0.047). CONCLUSION:
      The existence of grade 5 in the surgical specimen whatever the percentage was a
      poor prognostic factor associated with increased tumor aggressiveness and reduced
      biochemical recurrence-free survival. LEVEL OF EVIDENCE: 5.

PMID- 24861684
TI  - [Pigtail suture stent: decisive progress towards double-pigtail stent tolerance
      and unexpected properties of the suture in the ureter].
AB  - OBJECTIVE: Double-pigtail stent intolerance reduces the quality of life of
      patients. By decreasing the amount of material within the bladder, it should be
      possible to attenuate the symptoms linked to the stent. We evaluated the
      tolerance of a new stent with a dedicated questionnaire. PATIENTS ET METHODS: The
      major innovation of the pigtail suture stent (PSS and MiniPSS) was in the
      replacement of the lower part of the double-pigtail stent with a 0.3 F suture.
      One hundred and eight patients agreed to be fitted with a PSS. The double-pigtail
      stents of 24 patients complaining strongly of symptoms were replaced with PSS
      (group 1) and sixty-eight other patients were fitted directly with the PSS after
      an endoscopic intervention on the ureter (groups 2 and 3). Sixteen patients with
      non-obstructive kidney stone received MiniPSS (group 4). RESULTS: Completed
      questionnaires were obtained from 94 patients. In group 1, the replacement of the
      double-pigtail stent with a PSS significantly decreased urinary symptom scores
      (34.4+/-9.0 vs 20.3+/-7.4, P<0.0000007), and pain scores (10.1+/-5.1 vs 4.8+/
      3.2, P=0.0001). The scores of the two first groups fitted with a PSS were
      similar. Following PSS or MiniPSS implantation, a clear dilation of the ureteral
      meatus was probably induced by the sutures, facilitating the introduction of an
      ureteroscope or a flexible ureteroscope sheath (12 F). Following extracorporeal
      shockwave lithotripsy, the stone fragments gradually slid down the PSS sutures,
      without renal colic. CONCLUSION: The PSS seems to improve the tolerance of
      ureteral stent. Unexpectedly, following PSS implantation, we observe a clear
      dilation of the ureter. We believe that use of a double-pigtail stent should no
      longer be considered the only way to drain the ureter. Instead, the form of the
      stent should depend on the patient's disease. LEVEL OF EVIDENCE: 5.

PMID- 24861685
TI  - [Recent evolution of the epidemiological profile of extended-spectrum beta
      lactamase producing uropathogenic enterobacteria in Marrakech, Morocco].
AB  - INTRODUCTION: Urinary tract infection by extended-spectrum beta-lactamase
      producing enterobacteriaceae (ESBL-E) is a growing infection risk and may even
      lead in many cases to therapeutic impasses because of their multidrug resistance.
      AIM OF THE STUDY: Follow, over a 5-year period, the evolution of the
      epidemiological profile of uropathogenic ESBL-E and describe their current level
      of antibiotic resistance. MATERIALS AND METHODS: A retrospective work was made
      over a period of 5 years (from 1st January 2008 to 31st December 2012). It
      focused on all the ESBL-E strains isolated from all the urinary samples at the
      microbiology laboratory of Avicenne hospital, Marrakech (Morocco). RESULTS: We
      noticed in 5 years, an important increase in the prevalence of ESBL-E. The higher
      prevalence of ESBL-E (51%) was recorded in the urology department. The study of
      the antibiotic resistance of the ESBL-E had shown antibiotic co-resistances to
      the ciprofloxacin (82%), to sulfamethoxazole-trimethropim (85%), to gentamicin
      (74%), to amikacine (51%). Our results also showed, for the first time in our
      region, an emergence in the resistance of enterobacteria producing ESBL to
      imipenem (10%). CONCLUSION: The significant increase in the prevalence of ESBL-E
      has become a concern at the hospitals and in community medicine as well. The
      study of the resistance of ESBL-E strains antibiotics showed high rates of co
      resistance to antibiotics, including the usual urology molecules. LEVEL OF PROOF:
      5.

PMID- 24861687
TI  - [Laparoscopic nephrectomy for polycystic kidneys: principles and results].
AB  - OBJECTIVE: To evaluate the feasibility and morbidity of laparoscopic nephrectomy
      in patients with autosomal dominant polycystic kidney disease (ADPK). PATIENTS
      AND METHOD: This is a retrospective multi-centre study (University Hospitals of
      Lyons, Toulouse, Nantes and Rennes). Sixty-eight patients who had undergone
      laparoscopic nephrectomy for polycystic kidney disease between November 1999 and
      May 2009 were included. This involved unilateral nephrectomy 64 cases, one-stage
      bilateral in one case and two-stage bilateral in three cases. RESULTS: The mean
      operating time was 218+/-74min (100-420) Conversion was necessary in 7 cases. The
      mean weight of the removed kidney was 1291+/-646g (240-3400). We regret to report
      20 postoperative complications, including one death on postoperative day 50,
      following an abscess in the renal pelvis, 6 retroperitoneal haemoatomas and 5
      arteriovenous fistula thromboses. Postoperative analgesia involved PCA treatment
      with morphine for a mean period of 1.59+/-0.8 days (0.5-4). The mean length of
      hospital stay was 8.3+/-6.1 days (3-50). CONCLUSION: This study shows the
      feasibility of the laparoscopic approach for nephrectomy in ADPK. This procedure
      should be performed by experienced laparoscopic surgeons. Indeed, the
      complication rate is moderate but there is still a risk of severe complications.
      LEVEL OF EVIDENCE: 5.

PMID- 24861688
TI  - [Comparative analysis of photoselective vaporization of the prostate with the
      Greenlight laser and open prostatectomy for high volume prostate hypertrophy].
AB  - PURPOSE: Comparative medical economic study between total prostatectomy and laser
      in the treatment of benign prostatic hyperplasia in patients whose prostate is
      more than 80g. MATERIALS AND METHODS: This study compared data registered
      retrospectively for the group AVH and prospective data for PVP patients. The
      patients whose prostate weighed more than 80g by echography were selected. The
      adopted point of view was the one of the hospital and the temporal horizon was of
      one year after the surgical operation. Direct costs per- and post-surgery were
      taken into account including specific surgical care and secondary surgical
      revision. The medical data per- and postoperative were also compared. Primary
      outcome measure was incremental cost per procedure. RESULTS: Forty-one patients
      in the AVH group and 53 in the PVP group. The mean length of stay (LOS) is
      significantly shorter in the PVP group (3.0+/-1.0 days vs 10.4+/-4.0; P<0.001).
      Re-operation rate was significantly lower in the PVP group (1.9% vs 19.5%
      P<0.001). The cost analysis shows a mean additional cost of 1450 euros for the
      AVH group. CONCLUSION: PVP was cost-effective because it was more economic and it
      lead to lower re-operation rate until one year of follow-up than in the AVH
      group. Nevertheless, these data deserve to be nuanced by unfavorable results of
      the AVH in comparison with those of the literature.

PMID- 24861686
TI  - [Current state of compensation of on-duty and on-call urologists in France: a
      study from AFUF].
AB  - INTRODUCTION: The French Association of Urologists-in-training (AFUF) aimed to
      assess the current state of remunerations of on-call and on-duty residents,
      assistants and lecturers in urology in France. MATERIAL AND METHODS: Data were
      collected from February to May 2013 through a questionnaire sent to all members
      of the AFUF (327 members). Remunerations were given in gross values. RESULTS:
      Forty-three residents took part in the study, 16 assistants and 16 lecturers,
      representing 62 % of the whole centers (54 hospitals out of the 92 centers
      practicing urology in France). Most of responders were on security or operational
      on-call. Twenty hospitals were practicing multi-organ removal. Median
      remunerations of residents were about 59.51? per on-call when moving at hospital
      for work and about 119.02? per onsite duty. Assistants and lecturers were paid a
      flat fee rate for 37.5 % of them (140? for assistants [with variability from 40
      to 195?] and 130? for lecturers [42.5-180]) or an hourly rate depending on the
      hours spent at hospital for the others (62.5 %): first, second move or move<3h
      were paid 100? for assistants and 65? for lecturers, 233.5? and 236? respectively
      for the third one or above 3h, 365? and 473? respectively above 8h. Multi-organ
      removals were paid a flat fee rate (60 %) or an hourly rate (40 %) as well.
      Beyond a threshold of 2-3hours, the hourly rate was more interesting than the
      flat fee rate. CONCLUSION: There were disparities in remuneration of on-call and
      on-duty urologists. Greater variability affected on-call flat fee rate
      remuneration beyond a certain threshold of hours and remuneration of multi-organ
      removal. These disparities should be considered in order to get a national
      harmonization.

PMID- 24861689
TI  - [Limits of informations collected from online national database of the ATIH
      (Agence technique de l'information sur l'hospitalisation): about the paper
      "Practice uptake in France before and after the 2010 French guidelines on kidney
      cancer"].

PMID- 24861690
TI  - [Giant renal angiomyolipoma with right heart failure].
AB  - We report the case of a 63-year-old woman presenting a 26cm right renal
      angiomyolipoma with intratumoral arteriovenous fistula responsible for a high
      output right heart failure. A radical surgical treatment after preoperative
      embolization allowed rapid improvement of cardiac symptoms with an uneventful
      postoperative course.

PMID- 24861691
TI  - Predicting reading comprehension academic achievement in late adolescents with
      velo-cardio-facial (22q11.2 deletion) syndrome (VCFS): a longitudinal study.
AB  - BACKGROUND: The primary objective of the current study was to examine the
      childhood predictors of adolescent reading comprehension in velo-cardio-facial
      syndrome (VCFS). Although much research has focused on mathematics skills among
      individuals with VCFS, no studies have examined predictors of reading
      comprehension. METHODS: 69 late adolescents with VCFS, 23 siblings of youth with
      VCFS and 30 community controls participated in a longitudinal research project
      and had repeat neuropsychological test batteries and psychiatric evaluations
      every 3 years. The Wechsler Individual Achievement Test-2nd edition (WIAT-II)
      Reading Comprehension subtest served as our primary outcome variable. RESULTS:
      Consistent with previous research, children and adolescents with VCFS had mean
      reading comprehension scores on the WIAT-II, that were approximately two standard
      deviations below the mean and word reading scores approximately one standard
      deviation below the mean. A more novel finding is that relative to both control
      groups, individuals with VCFS demonstrated a longitudinal decline in reading
      comprehension abilities yet a slight increase in word reading abilities. In the
      combined control sample, WISC-III FSIQ, WIAT-II Word Reading, WISC-III Vocabulary
      and CVLT-C List A Trial 1 accounted for 75% of the variance in Time 3 WIAT-II
      Reading Comprehension scores. In the VCFS sample, WISC-III FSIQ, BASC-Teacher
      Aggression, CVLT-C Intrusions, Tower of London, Visual Span Backwards, WCST Non
      perseverative Errors, WIAT-II Word Reading and WISC-III Freedom from
      Distractibility index accounted for 85% of the variance in Time 3 WIAT-II Reading
      Comprehension scores. A principal component analysis with promax rotation
      computed on the statistically significant Time 1 predictor variables in the VCFS
      sample resulted in three factors: Word reading decoding/Interference control,
      Self-Control/Self-Monitoring and Working Memory. CONCLUSIONS: Childhood
      predictors of late adolescent reading comprehension in VCFS differ in some
      meaningful ways from predictors in the non-VCFS population. These results offer
      some guidance for how best to consider intervention efforts to improve reading
      comprehension in the VCFS population.

PMID- 24861692
TI  - Bone neo-formation and mineral degradation of 4Bone.((r)) Part I: material
      characterization and SEM study in critical size defects in rabbits.
AB  - OBJECTIVE: This study reports the characterization process and in vivo
      application of a new high-porosity biphasic calcium phosphate (4Bone((r)) - HA
      60%/beta-TCP 40%) inserted into the critical size defect of a rabbit tibiae.
      MATERIAL AND METHODS: Two critical size defects of 6 mm diameter were created in
      each tibia of 15 New Zealand rabbits, and a total of 60 defects were divided into
      a test group filled with 4Bone((r)) (n = 30) and a control group (n = 30). The
      material and the implants were characterized by scanning electron microscope
      (SEM) fitted with energy-dispersive X-ray spectroscopy (EDX). RESULTS: The
      biomaterial's grain size decreased progressively with the graft integration
      process over the 60-day study period. Element analysis revealed increased
      percentages of Ca/P (2.86 +/- 0.32 vs. 1.97 +/- 0.59) in new bone and at the
      interface (P < 0.05). Element mapping showed that Ca and P were concentrated in
      the medullary and cortical zones in the test group but were concentrated only in
      cortical zones in the control group. CONCLUSIONS: Critical size defects in a
      rabbit tibia model can be sealed using this highly porous biphasic calcium
      phosphate; it supports new bone formation, creates a bridge between defect
      borders, and facilitates bone in growth.

PMID- 24861693
TI  - Microparticle-associated tissue factor activity and overt disseminated
      intravascular coagulation in patients with acute myelocytic leukemia.

PMID- 24861694
TI  - Misinterpretation of the HAS-BLED bleeding score by end-users.

PMID- 24861696
TI  - Pattern of response in patients with moderate-to-severe psoriasis treated with
      etanercept.
AB  - BACKGROUND: Etanercept (ETN) 50 mg once weekly (QW) or 50 mg twice weekly (BIW)
      for 12 weeks, followed by 50 mg QW in all subjects to Week 24 improved psoriasis
      in patients with concomitant psoriatic arthritis in the PRESTA trial. OBJECTIVES:
      To use data from PRESTA to evaluate the effect of ETN in the treatment of
      psoriasis by Psoriasis Area Severity Index (PASI) body-region and component, and
      determine if PASI responses correlate with the Dermatology Life Quality Index
      (DLQI). METHODS: Median time to 75% improvement in PASI (PASI75), body- and
      component-specific subscales over 24 weeks were estimated. Pearson correlation
      coefficients determined the association between DLQI score and PASI total score,
      body- and component-specific subscales with ETN treatment at baseline and up to
      Week 24. RESULTS: In total, 748 patients from PRESTA were included (ETN 50 mg
      QW/QW, n = 371; BIW/QW, n = 377). Patients achieved PASI75 total score and 75%
      improvements in all body regions and components faster on ETN 50 mg BIW/QW than
      QW/QW (all P < 0.05). Median time to 75% improvement was faster for the head and
      trunk followed by upper and lower extremities, and for induration and
      desquamation followed by erythema and total area. Weak to moderately positive
      correlations between improvements in DLQI and PASI total score (r = 0.223-0.463),
      all PASI body-specific (r = 0.114-0.432) and component-specific (r = 0.178-0.478)
      subscales were observed over 24 weeks. CONCLUSIONS: Etanercept treatment-response
      appears to occur in a body- and component-specific manner. Changes in quality of
      life are not captured by PASI or its subscales.

PMID- 24861697
TI  - Umbilical cord blood transplantation induces a durable remission in hepatosplenic
      gamma-delta T cell lymphoma with associated hemophagocytic lymphohistiocytosis.

PMID- 24861695
TI  - Elevated levels of full-length and thrombin-cleaved osteopontin during acute
      dengue virus infection are associated with coagulation abnormalities.
AB  - INTRODUCTION: Dengue virus (DENV) is transmitted by the mosquito vector, and
      causes a wide range of symptoms that lead to dengue fever (DF) or life
      threatening dengue hemorrhagic fever (DHF). The host and viral correlates that
      contribute to DF and DHF are complex and poorly understood, but appear to be
      linked to inflammation and impaired coagulation. Full-length osteopontin (FL
      OPN), a glycoprotein, and its activated thrombin-cleaved product, trOPN,
      integrate multiple immunological signals through the induction of pro
      inflammatory cytokines. MATERIALS AND METHOD: To understand the role of OPN in
      DENV-infection, we assessed circulating levels of FL-OPN, trOPN, and several
      coagulation markers (D-dimer, thrombin-antithrombin complex [TAT], thrombomodulin
      [TM], and ferritin in blood obtained from 65 DENV infected patients in the
      critical and recovery phases of DF and DHF during a dengue virus epidemic in the
      Philippines in 2010. RESULTS: Levels of FL-OPN, trOPN, D-dimer, TAT, and TM were
      significantly elevated in the critical phase in both the DF and DHF groups, as
      compared with healthy controls. During the recovery phase, FL-OPN levels declined
      while trOPN levels increased dramatically in both the DF and DHF groups. FL-OPN
      levels were directly correlated with D-dimer and ferritin levels, while the
      generation of trOPN was associated with TAT levels, platelet counts, and viral
      RNA load. CONCLUSION: Our study demonstrated the marked elevation of plasma
      levels of FL-OPN and thrombin-cleaved OPN product, trOPN, in DENV-infection for
      the first time. Further studies on the biological functions of these
      matricellular proteins in DENV-infection would clarify its pathogenesis.

PMID- 24861698
TI  - KIVA VCF system in the treatment of T12 osteoporotic vertebral compression
      fracture.

PMID- 24861699
TI  - Answer to the letter of the editor T. Cook concerning "a prospective randomized
      controlled study on the treatment outcome of SpineCor brace versus rigid brace
      for adolescent idiopathic scoliosis with follow-up according to the SRS
      standardized criteria" by Jing Guo et al., Eur Spine J, doi:10.1007/s00586-013
      3146-1.

PMID- 24861700
TI  - Time of transition.

PMID- 24861701
TI  - Introduction: themed issue dedicated to Professor Kahp-Yang Suh.

PMID- 24861702
TI  - Reuse versus single-use catheters for intermittent catheterization: what is safe
      and preferred? Review of current status.
AB  - STUDY DESIGN: This is a narrative review summarizing prevalence and background of
      reusing catheters for intermittent catheterization. It also compares
      complications related to reuse versus single use. OBJECTIVES AND SETTING: The
      objective of the review is to highlight the on-going debate regarding whether
      reuse of catheters is as safe as single-use technique and investigate why reuse
      is common in some countries (for example, Australia, Canada and the United
      States). METHODS: The review is the result of systematic searches in several
      databases (for example, MEDLINE, EMBASE and CINAHL) using predefined key words
      and search strategy. RESULTS: The literature does not explicitly recommend reuse
      but instead proposes patient-oriented choice. Even so, the prevalence of reuse is
      ~50% in some regions. Both off-label reuse and reuse of catheters intended for
      multiple use occur. The former is not legally supported. There seems to be no
      consensus on how many times a catheter can be reused or how to clean it. Poor
      compliance and efficacy of cleaning techniques have been reported, increasing the
      risk for introducing bacterial contamination. The literature supports the use of
      single-use hydrophilic catheters to reduce the risk of urethral trauma and
      urinary tract infection with a reported incidence of the latter between 40 and
      60%, as compared with 70-80% for reuse catheters. Further clinical studies are
      however needed to verify/reject a difference. CONCLUSION: Complications
      associated with reuse need to be further investigated. Although awaiting
      evidence, it is recommended to use a confirmed safe, patient-preferred,
      noninfecting and nontraumatic technique for intermittent catheterization.

PMID- 24861703
TI  - A preliminary evaluation of the surgery to reconstruct thoracic breathing in
      patients with high cervical spinal cord injury.
AB  - STUDY DESIGN: A prospective study. OBJECTIVES: To evaluate the effect of the
      surgery to reconstruct thoracic breathing in patients with high cervical spinal
      cord injury (CSCI). SETTING: China Rehabilitation Research Center, Beijing,
      China. METHODS: The posterior ribs (from the fifth to the eighth) were suspended
      on the inferior angle of the scapula on each side using titanium cables, as well
      as muscles and myofascial tissue in the subscapular area. After the surgery, the
      patients were trained for synchronous contraction of the trapezius and diaphragm
      muscles, and electromyography (EMG) was performed to evaluate the
      synchronization. The clinical symptoms and pulmonary function were assessed
      within 1 week before surgery and at 2, 12 and 24 postoperative weeks. RESULTS:
      Six patients with complete high CSCI received rib suspension surgery 84+/-26.7
      days after spinal cord injury. Before the surgery, all of the patients presented
      with weakened cough, retention of respiratory secretions and dyspnea, while these
      symptoms alleviated postoperatively. The vital capacity (VC) was enhanced to be
      1680+/-282 ml at 2 weeks after the surgery, compared with 1085+/-92 ml (P=0.013).
      The EMG showed a synchronous muscle electrical activity between the trapezius
      muscles and diaphragm during deep breaths. CONCLUSION: The rib suspension surgery
      partially restored the thoracic breathing of the patients with high CSCI, thereby
      improving VC, cough and expectoration.

PMID- 24861704
TI  - Are afebrile seizures associated with minor infections a single seizure category?
      A hospital-based prospective cohort study on outcomes of first afebrile seizure
      in early childhood.
AB  - OBJECTIVE: To explore if afebrile seizures associated with minor infections are a
      single category of seizure, or a set of different kinds of seizures. METHODS: We
      conducted this prospective cohort study on three kinds of first afebrile seizure:
      first afebrile seizure associated with gastrointestinal infection (AS-GI), first
      afebrile seizure associated with nongastrointestinal infection (AS-nGI), and
      first unprovoked seizure (US). The Kaplan-Meier estimate risks of recurrent
      seizures were analyzed and compared pairwise. The characteristics of recurrent
      seizures were also compared pairwise. RESULTS: The Kaplan-Meier estimate risks of
      recurrent seizure at 2 years of the AS-GI, AS-nGI, and US groups were 6.9%,
      23.7%, and 37.8%, respectively. The pairwise differences were significant between
      the AS-GI and US groups (p < 0.001) and between the AS-GI and AS-nGI groups (p =
      0.001), but not significant between the US and AS-nGI groups (p = 0.066). Among
      unprovoked subsequent seizures in patients with recurrence, the pairwise
      differences were significant between the AS-GI and US groups (p < 0.001) and
      between the AS-GI and AS-nGI groups (p = 0.005), but not significant between the
      US and AS-nGI groups (p = 0.417). SIGNIFICANCE: Afebrile seizures associated with
      minor infections are indeed of two distinguishable kinds: AS-GI, if free of risk
      factors such as a family history of epilepsy, had a better prognosis and should
      be categorized as an acute symptomatic seizure, whereas patients with first AS
      nGI, like patients with first US, may have recurrent unprovoked seizures, which
      suggests this category's essential difference from AS-GI.

PMID- 24861705
TI  - The GUN4 protein plays a regulatory role in tetrapyrrole biosynthesis and
      chloroplast-to-nucleus signalling in Chlamydomonas reinhardtii.
AB  - The GENOMES UNCOUPLED 4 (GUN4) protein is found only in aerobic photosynthetic
      organisms. We investigated the role of GUN4 in metabolic activities of the Mg
      branch of the tetrapyrrole biosynthesis pathway and the plastid signal-mediated
      changes of nuclear gene expression in Chlamydomonas reinhardtii. In light, gun4
      accumulates only 40% of the wild-type chlorophyll level. Light- or dark-grown
      gun4 mutant accumulates high levels of protoporphyrin IX (Proto), and displays
      increased sensitivity to moderate light intensities. Despite the photooxidative
      stress, gun4 fails to downregulate mRNA levels of the tetrapyrrole biosynthesis
      and the photosynthesis-associated nuclear genes (PhANGs). In contrast, upon
      illumination, the Proto-accumulating and light-sensitive chlD-1 mutant displays
      the expected downregulation of the same nuclear genes. Although chlD-1 and the
      wild type have similar GUN4 transcript levels, the GUN4 protein in chlD-1 is
      hardly detectable. Overexpression of GUN4 in chlD-1 modifies the downregulation
      of nuclear gene expression, but also increases light tolerance. Therefore, GUN4
      is proposed to function in 'shielding' Proto, and most likely MgProto, by
      reducing reactivity with O2 . Furthermore, GUN4 seems to be involved in sensing
      elevated levels of these photoreactive tetrapyrrole intermediates, and
      contributing to (1) O2 -mediated retrograde signalling, originating from
      chlorophyll biosynthesis.

PMID- 24861707
TI  - Fine-scale habitat use by orang-utans in a disturbed peat swamp forest, central
      Kalimantan, and implications for conservation management.
AB  - This study was conducted to see how orang-utans (Pongo pygmaeus wurmbii) were
      coping with fine-scale habitat disturbance in a selectively logged peat swamp
      forest in Central Kalimantan, Borneo. Seven habitat classes were defined, and
      orang-utans were found to use all of these, but were selective in their
      preference for certain classes over others. Overall, the tall forest classes
      (>=20 m) were preferred. They were preferred for feeding, irrespective of canopy
      connectivity, whereas classes with a connected canopy (canopy cover >=75%),
      irrespective of canopy height, were preferred for resting and nesting, suggesting
      that tall trees are preferred for feeding and connected canopy for security and
      protection. The smaller forest classes (<=10 m high) were least preferred and
      were used mainly for travelling from patch to patch. Thus, selective logging is
      demonstrated here to be compatible with orang-utan survival as long as large food
      trees and patches of primary forest remain. Logged forest, therefore, should not
      automatically be designated as 'degraded'. These findings have important
      implications for forest management, forest classification and the designation of
      protected areas for orang-utan conservation.

PMID- 24861706
TI  - Chemical communication of predation risk in zebrafish does not depend on cortisol
      increase.
AB  - We investigated chemical cues among groups of zebrafish (Danio rerio) when
      communicating information about the risk of predation. We found that visual cues
      of the predator (tiger Oscar, Astronotus ocellatus) did not increase whole-body
      cortisol levels in groups of zebrafish but that water conditioned by these
      (donor) zebrafish stressed (target) conspecifics, thereby increasing whole-body
      cortisol. This finding was confirmed when these zebrafish groups were in
      different aquaria and communicated exclusively via water transfer. This result
      indicates that the stress induced in the target zebrafish does not depend on an
      increase in whole-body cortisol levels in the donor zebrafish. Because cortisol
      participation is rejected in this predation-risk communication, other chemicals
      from the stress systems should be investigated. 

PMID- 24861708
TI  - Effects of brief time delays on matching-to-sample abilities in capuchin monkeys
      (Sapajus spp.).
AB  - Traditionally, studies of delayed matching-to-sample (DMTS) tasks in nonhuman
      species have focused on the assessment of the limits of the retrieval of
      information stored in short- and long-term memory systems. However, it is still
      unclear if visual recognition in these tasks is affected by very brief delay
      intervals, which are typically used to study rapidly decaying types of visual
      memory. This study aimed at evaluating if tufted capuchin monkeys' ability to
      recognise visual stimuli in a DMTS task is affected by (i) the disappearance of
      the sample stimulus and (ii) the introduction of delay intervals (0.5, 1.0, 2.0
      and 3.0s) between the disappearance of the sample and the presentation of the
      comparison stimuli. The results demonstrated that the simple disappearance of the
      sample and the introduction of a delay of 0.5s did not affect capuchins'
      performance either in terms of accuracy or response time. A delay interval of
      1.0s produced a significant increase in response time but still did not affect
      recognition accuracy. By contrast, delays of 2.0 and 3.0s determined a
      significant increase in response time and a reduction in recognition accuracy.
      These findings indicate the existence in capuchin monkeys of processes enabling a
      very accurate retention of stimulus features within time frames comparable to
      those reported for humans' sensory memory (0.5-1.0s). The extent to which such
      processes can be considered analogous to the sensory memory processes observed in
      human visual cognition is discussed. 

PMID- 24861709
TI  - D-serine enhances fear extinction by increasing GluA2-containing AMPA receptor
      endocytosis.
AB  - Activation of the N-methyl-D-aspartate receptor (NMDAR) glycine site has been
      shown to enhance memory extinction in physiological and pathological conditions.
      In the current study, we examined the effects of D-serine, an endogenous NMDAR
      glycine site agonist, on fear extinction and alpha-amino-3-hydroxy-5-methyl-4
      isoxazole propionic acid receptor (AMPAR) endocytosis in the hippocampus during
      the process of fear extinction. In inhibitory avoidance task, systemic
      administration of D-serine (800 mg/kg, i.p.) significantly accelerated memory
      extinction. The Western blot analyses showed that the acceleration of memory
      extinction was accompanied by an increase in postsynaptic AMPAR endocytosis in
      the hippocampus. Furthermore, the application of a synthetic peptide Tat-GluA23Y
      (3.0 MUmol/kg, i.p.) that interferes with the endocytosis of AMPARs succeeded in
      preventing the enhancement of fear extinction and AMPAR endocytosis induced by D
      serine. These results suggest that d-serine might enhance fear extinction through
      increasing GluA2-containing AMPA receptor endocytosis, and that d-serine may be a
      potential therapeutic agent against learning and memory disorders.

PMID- 24861710
TI  - Influence of emotional states on inhibitory gating: animals models to clinical
      neurophysiology.
AB  - Integrating research efforts using a cross-domain approach could redefine
      traditional constructs used in behavioral and clinical neuroscience by
      demonstrating that behavior and mental processes arise not from functional
      isolation but from integration. Our research group has been examining the
      interface between cognitive and emotional processes by studying inhibitory
      gating. Inhibitory gating can be measured via changes in behavior or neural
      signal processing. Sensorimotor gating of the startle response is a well-used
      measure. To study how emotion and cognition interact during startle modulation in
      the animal model, we examined ultrasonic vocalization (USV) emissions during
      acoustic startle and prepulse inhibition. We found high rates of USV emission
      during the sensorimotor gating paradigm and revealed links between prepulse
      inhibition (PPI) and USV emission that could reflect emotional and cognitive
      influences. Measuring inhibitory gating as P50 event-related potential
      suppression has also revealed possible connections between emotional states and
      cognitive processes. We have examined the single unit responses during the
      traditional gating paradigm and found that acute and chronic stress can alter
      gating of neural signals in regions such as amygdala, striatum and medial
      prefrontal cortex. Our findings point to the need for more cross-domain research
      on how shifting states of emotion can impact basic mechanisms of information
      processing. Results could inform clinical work with the development of tools that
      depend upon cross-domain communication, and enable a better understanding and
      evaluation of psychological impairment. 

PMID- 24861712
TI  - Amino acid metabolic dysfunction revealed in the prefrontal cortex of a rat model
      of depression.
AB  - Major depressive disorder (MDD) is a debilitating mood disorder. However, the
      molecular mechanism(s) underlying depression remain largely unknown. Here, we
      applied a GC-MS-based metabonomic approach in the chronic unpredictable mild
      stress (CUMS) model, a well-established rodent model of depression, to
      investigate significant metabolic changes in the rat prefrontal cortex (PFC).
      Multivariate statistical analysis - including principal component analysis,
      partial least squares-discriminate analysis, and pair-wise orthogonal projections
      to latent structures discriminant - was applied to identify differential PFC
      metabolites between CUMS rats and healthy controls. As compared to healthy
      control rats, CUMS rats were characterized by lower levels of isoleucine and
      glycerol in combination with higher levels of N-acetylaspartate and beta-alanine.
      These findings should provide insight into the pathophysiological mechanism(s)
      underlying MDD and preliminary leads relevant to diagnostic biomarker discovery
      for depression. 

PMID- 24861711
TI  - Sex-dependent changes in ADHD-like behaviors in juvenile rats following cortical
      dopamine depletion.
AB  - Reduced cortical dopamine levels have been observed in individuals with attention
      deficit hyperactivity disorder (ADHD). Global dopamine depletions by 6
      hydroxydopamine (6-OHDA; with noradrenergic protection) in neonatal rats produces
      locomotor hyperactivity, with less known about how cortical depletion modulates
      risky behaviors. Here, we determined the effect of a medial prefrontal cortex
      (PFC) 6-OHDA depletions (30-60%) or sham microinjection at postnatal day 11 on
      behavior in male and female juvenile rats. Separate groups were studied for delay
      discounting (impulsive choice), novelty-preference, and preferences for cues and
      environments associated with cocaine (10, 20, and 40 mg/kg), their extinction,
      and reinstatement with place conditioning. Because PFC D1 receptors play a role
      in these behaviors, confocal microscopy was used to measure D1-immunoreactive
      projections to the nucleus accumbens core. Both 6-OHDA males and females
      increased delay discounting relative to sham controls, although only 6-OHDA
      females increased novelty preferences. Preferences for cocaine-associated
      environments, their extinction, and reinstatement with a priming dose of cocaine
      were reduced in 6-OHDA subjects overall. However, impulsive choice at 5s
      positively correlated with preferences for cocaine-associated environments in 6
      OHDA subjects, but not sham controls. As possible compensation for low dopamine
      levels, D1-immunoreactivity on traced neurons increased in 6-OHDA females;
      dopamine levels did not remain low in adolescent 6-OHDA males and D1 did not
      change. We believe that these modest depletions restricted to the PFC demonstrate
      the role of dopamine, and not norepinephrine, in understanding these behaviors in
      other animal models where cortical dopamine is reduced during development.

PMID- 24861713
TI  - Synthesis, photophysical properties and incorporation of a highly emissive and
      environment-sensitive uridine analogue based on the Lucifer chromophore.
AB  - The majority of fluorescent nucleoside analogues used in nucleic acid studies
      have excitation maxima in the UV region and show very low fluorescence within
      oligonucleotides (ONs); hence, they cannot be utilised with certain fluorescence
      methods and for cell-based analysis. Here, we describe the synthesis,
      photophysical properties and incorporation of a highly emissive and environment
      sensitive uridine analogue, derived by attaching a Lucifer chromophore (1,8
      naphthalimide core) at the 5-position of uracil. The emissive nucleoside displays
      excitation and emission maxima in the visible region and exhibits high quantum
      yield. Importantly, when incorporated into ON duplexes it retains appreciable
      fluorescence efficiency and is sensitive to the neighbouring base environment.
      Notably, the nucleoside signals the presence of purine repeats in ON duplexes
      with an enhancement in fluorescence intensity, a property rarely displayed by
      other nucleoside analogues.

PMID- 24861714
TI  - A novel rat full-thickness hemi-abdominal wall/hindlimb osteomyocutaneous
      combined flap: influence of allograft mass and vascularized bone marrow content
      on vascularized composite allograft survival.
AB  - Vascularized bone marrow transplantation (VBMT) appears to promote tolerance for
      vascularized composite allotransplantation (VCA). However, it is unclear whether
      VBMT is critical for tolerance induction and, if so, whether there is a finite
      amount of VCA that VBMT can support. We investigated this with a novel VCA
      combined flap model incorporating full-thickness hemiabdominal wall and hindlimb
      osteomyocutaneous (HAW/HLOMC) flaps. Effects of allograft mass (AM) and VBMT on
      VCA outcome were studied by comparing HAW/HLOMC VCAs with fully MHC-mismatched BN
      donors and Lewis recipients. Control groups did not receive treatments following
      transplantation. Treatment groups received a short course of cyclosporine A
      (CsA), antilymphocyte serum, and three doses of adipocyte-derived stem cells (POD
      1, 8, and 15). The results showed that all flaps in control allogeneic groups
      rejected soon after VCAs. Treatment significantly prolonged allograft survival.
      Three of eight recipients in HLOMC treatment group had allografts survive long
      term and developed donor-specific tolerance. Significantly higher peripheral
      chimerism was observed in HLOMC than other groups. It is concluded that the
      relative amount of AM to VBMT is a critical factor influencing long-term
      allograft survival. Accordingly, VBMT content compared with VCA mass may be an
      important consideration for VCA in humans. 

PMID- 24861715
TI  - Communicative strategies used by spouses of individuals with communication
      disorders related to stroke-induced aphasia and Parkinson's disease.
AB  - BACKGROUND: A communicative disability interferes with the affected person's
      ability to take active part in social interaction, but non-disabled communication
      partners may use different strategies to support communication. However, it is
      not known whether similar strategies can be used to compensate for different
      types of communicative disabilities, nor what factors contribute to the
      development of a particular approach by communication partners. AIMS: To develop
      a set of categories to describe the strategies used by communication partners of
      adults who have problems expressing themselves due to neurogenic communicative
      disabilities. The reliability of assessment was a particular focus. METHODS &
      PROCEDURES: The material explored consisted of 21 video-recorded everyday
      conversations involving seven couples where one spouse had a communicative
      disability. Three of the dyads included a person with dysarthria and anomia
      related to later stages of Parkinson's disease, while four of them included a
      person with stroke-induced aphasia involving anomia. First a qualitative
      interaction analysis was performed to explore the strategies used by the
      communication partners when their spouses had problems expressing themselves. The
      strategies were then categorized, the reliability of the categorizations was
      explored and the relative frequency of the various strategies was examined.
      OUTCOMES & RESULTS: The analysis of the conversational interactions resulted in a
      set of nine different strategies used by the communication partners without a
      communicative disability. Each of these categories belonged to one of three
      overall themes: No participation in repair; Request for clarification or
      modification; and Providing candidate solutions. The reliability of the
      categorization was satisfactory. There were no statistically significant
      differences between diagnoses in the frequency of use of strategies, but the
      spouses of the persons with Parkinson's disease tended to use open-class
      initiations of repair more often than the spouses of the persons with aphasia.
      CONCLUSIONS & IMPLICATIONS: The types of strategies used by spouses of persons
      with neurogenic communicative disabilities seem to be more strongly associated
      with individual characteristics of communicative ability than with the type of
      disorder involved. The set of categories developed in this study needs to be
      trialled on larger groups of participants, and modified if and as necessary,
      before it can be regarded as a valid system for the description of such
      strategies in general. Once this has been done it may become a useful instrument
      in the assessment of the strategies used by communication partners of individuals
      with communicative disabilities.

PMID- 24861716
TI  - The drowning whipple: perioperative fluid balance and outcomes following
      pancreaticoduodenectomy.
AB  - BACKGROUND AND OBJECTIVES: Given the high incidence of postoperative morbidity
      following pancreaticoduodenectomy (PD), efforts at improving patient outcomes are
      vital. We sought to determine the impact of perioperative fluid balance on
      outcomes following PD in order to identify a targeted strategy for reducing
      morbidity. METHODS: A retrospective review of consecutive PDs from 2008 to 2012
      was completed. Cumulative fluid balances were recorded at 0, 24, 48, and 72 hr
      postoperatively and patients were divided into quartiles. Multivariate analyses
      were performed accounting for age, gender, diagnosis, ASA class, estimated blood
      loss, colloid and blood product use, and hemoglobin nadir. The predefined primary
      outcome measures were 90-day morbidity (Clavien grade >= III), mortality, and
      hospital readmission. RESULTS: One hundred sixty-nine PDs were performed during
      the study period. The 90-day morbidity and mortality rates for the cohort were
      40.2% and 3.0%, respectively, while hospital length of stay was 13.6 +/- 6.7 days
      (mean +/- SD). Higher fluid balance at 48 and 72 hr postoperatively was an
      independent predictor of morbidity and length of stay on multivariate analysis.
      CONCLUSIONS: Higher postoperative fluid balance is associated with increased
      postoperative morbidity and longer hospital stay following PD. Efforts at
      maintaining a fluid-restrictive strategy should be emphasized in this population.

PMID- 24861718
TI  - Use of GlideScope(r) in adults: an overview.
AB  - This paper is an overview of the literature concerning the "know how" of the
      GlideScope(r) use in adults. We summarized the main evidences of the last 10
      years with particular attention to experts' suggestions about clinical practice
      of the GlideScope(r), noticing matters still debated on GlideScope(r) use. We
      used PubMed to search publications from January 2003 to June 2013 using the
      search terms "GlideScope", "video laryngoscope" and "videolaryngoscopy". These
      publications were searched manually or references to further publication not
      identified using PubMed. All works that made a point worth including were cited
      in the discussion. Our research confirms the value of GlideScope(r) use in airway
      management and highlights the debate about the use of videolaryngoscopes in
      routine cases and the operators who may use them in clinical practice. 

PMID- 24861717
TI  - Validity and fidelity of the upper airway in two high-fidelity patient
      simulators.
AB  - BACKGROUND: Human patient simulators are frequently used for airway management
      training and research. However, little is known about their fidelity and
      validity. The use of these simulators as a benchmark model remains highly
      questionable. The objective of this study was to evaluate the validity and
      fidelity of two patient simulators (compared to actual patients) for anaesthesia
      residents performing three airway management techniques. METHODS: Endotracheal
      intubation, laryngeal mask airway insertion and mask ventilation were performed
      by anaesthesia residents on 80 patients undergoing elective surgery. The
      anaesthesia residents also used these three techniques to secure the airways of
      two human patient simulators in a randomised crossover study. The durations,
      difficulties, realism and success rates of the procedures were assessed. RESULTS:
      Although the performance of endotracheal intubation was comparable in patients
      and both manikins, no chest rise was visible in 35% (HAL) and 32.5% (SimMan) of
      the manikins after inserting a laryngeal mask airway. This result was not
      observed in patients (P<0.001). Furthermore, effective mask ventilation was not
      possible in 60% of the cases using HAL, compared with 0% of cases using SimMan
      and 2.5% of patients (P<0.001). CONCLUSION: Patient simulators are not a valid
      alternative to human patients for conducting scientific evaluations of
      supraglottic airway management techniques. HAL and SimMan do have adequate
      validity for endotracheal intubation, but the fidelity and validity are low when
      a laryngeal mask is used or if mask ventilation is performed. Therefore, previous
      simulation-based airway device evaluation studies must be interpreted with great
      caution.

PMID- 24861719
TI  - Single-shot epidural-spinal anesthesia followed by oral oxycodone/naloxone and
      ketoprofen combination in patients undergoing total hip replacement: analgesic
      efficacy and tolerability.
AB  - BACKGROUND: Many patients undergoing hip replacement have inadequate
      postoperative pain control, leading to suboptimal recovery. Oxycodone is
      effective in controlling pain, but is associated with adverse events such as
      postoperative nausea and vomiting (PONV). In patients with chronic pain, oral
      oxycodone-naloxone combination (OXN) provides comparable analgesia with fewer
      side effects. This retrospective, single-centre study evaluated analgesic
      effectiveness and tolerability of single-shot epidural spinal anaesthesia
      followed by OXN after total hip replacement. METHODS: Consecutive patients
      received perioperative spinal-epidural anaesthesia, OXN 10/5 mg and oral
      ketoprofen 100 mg q 12h for 4 days. Efficacy and tolerability were assessed on
      the evening post surgery and days 1-3 after. Efficacy endpoints included pain
      intensity at rest and upon movement (Numerical Rating Scale [NRS] Score), rescue
      analgesia and patient satisfaction (0-3 point scale). RESULTS: Two hundred eighty
      two patients were included in the observation (57.2% women, mean age 62.9+/-12
      years). After surgery, pain intensity remained well controlled, both at rest
      (mean NRS: 1.1, 1.1, 1.2 and 1.2 on days 0-3 respectively; P=ns) and upon
      movement (2.1, 2.4, 2.1 and 2.0; P=ns). No patient reported severe pain
      throughout the observation. Rescue paracetamol was required on days 0-3 in 17.0%,
      18.4%, 12.4% and 12.1% of patients, respectively (P<0.009); no patient required
      additional intravenous rescue morphine. Seventy-two percent of patients were
      'very satisfied' with postoperative pain therapy. CONCLUSION: Single-shot
      epidural spinal anaesthesia followed by OXN-based analgesia after hip replacement
      provided effective pain management, with high patient satisfaction rates.

PMID- 24861720
TI  - A methodological approach for determination of maximal inspiratory pressure in
      patients undergoing invasive mechanical ventilation.
AB  - BACKGROUND: Maximal inspiratory pressure (MIP) can help to evaluate inspiratory
      muscle strength. However its determination in ventilated patients is cumbersome
      and needs special equipment. We hypothesized that MIP could be obtained by using
      the expiratory hold knob of the ventilator. The aim of this study was to verify
      whether: 1) the end expiratory occlusion technique can be used for MIP
      determination; and 2) if this technique provides different results compared to
      those obtained by the traditional method of MIP calculation. METHODS: We studied
      23 consecutive patients undergoing mechanical ventilation for acute respiratory
      failure. The MIP was determined by two different methods, both based on occluding
      the airway for 20 seconds. This occlusion was obtained either by pressing the
      expiratory hold knob of the ventilator; or by detaching the patient from the
      ventilator circuit and using a noiseless pneumatic shutter placed on the
      inspiratory line of a two-way valve that allows expiration but prevents
      inspiration. RESULTS: The average values of MIP obtained by using either the hold
      knob of the ventilator or the noiseless pneumatic shutter were -46+/-14 cmH2O and
      -56+/-13 cmH2O, respectively. The linear regression analysis showed a significant
      correlation between MIPVent and MIPOcc (r2=0.95), although the Bland- Altman
      analysis revealed that they are not clinically comparable. CONCLUSION: MIP can be
      easily determined at the bedside by pressing the expiratory hold knob of
      ventilator. However, MIPVent and MIPOcc are different in terms of absolute value
      probably because they were determined at diverse lung volume.

PMID- 24861721
TI  - Does the Child Behavior Checklist predict levels of preoperative anxiety at
      anesthetic induction and postoperative emergence delirium? A prospective cohort
      study.
AB  - BACKGROUND: preoperative anxiety at induction and postoperative emergence
      delirium (ED) in children are associated with postoperative behavioral changes
      and adjustment disorders. This study's aim is to assess the value of the Child
      Behavior Checklist (CBCL) score in order to predict anxiety during induction and
      emergence delirium after anesthesia in children undergoing elective day-care
      surgery. METHODS: Anxiety at induction, assessed by the modified Yale
      Preoperative Anxiety Scale (mYPAS), was studied as outcome in 401 children (60.1%
      male, age range: 1.5-16 years). For 343 of these children (59.8% male, age range:
      1.5-16 years) ED could be investigated postoperatively, as assessed by the
      Pediatric Anesthesia Emergence Delirium scale (PAED). Demographic data,
      healthcare contacts, anesthesia and surgical data were registered. Preoperative
      emotional/behavioral problems, during the 6 months prior to surgery, were
      assessed by the CBCL. Hierarchical, multiple regression was used to test whether
      anxiety and ED could be predicted by CBCL scores. RESULTS: Children with a higher
      CBCL score on preoperative internalizing problems (e.g. anxious/depression)
      showed preoperative more anxiety at induction (P=0.003). A higher CBCL score on
      preoperative emotional/behavioral problems was not associated with ED.
      CONCLUSION: The CBCL predicted anxiety at induction but not ED.

PMID- 24861722
TI  - Systematic study of lactate in ECMO: perhaps an opportunity to strengthen the
      decision-making process.

PMID- 24861723
TI  - Nanoscopic management of molecular packing and orientation of small molecules by
      a combination of linear and branched alkyl side chains.
AB  - We synthesized a series of acceptor-donor-acceptor-type small molecules (SIDPP
      EE, SIDPP-EO, SIDPP-OE, and SIDPP-OO) consisting of a dithienosilole (SI)
      electron-donating moiety and two diketopyrrolopyrrole (DPP) electron-withdrawing
      moieties each bearing linear n-octyl (O) and/or branched 2-ethylhexyl (E) alkyl
      side chains. X-ray diffraction patterns revealed that SIDPP-EE and SIDPP-EO films
      were highly crystalline with pronounced edge-on orientation, whereas SIDPP-OE and
      SIDPP-OO films were less crystalline with a radial distribution of molecular
      orientations. Near-edge X-ray absorption fine structure spectroscopy disclosed an
      edge-on orientation with a molecular backbone tilt angle of ~22 degrees  for both
      SIDPP-EE and SIDPP-EO. Our analysis of the molecular packing and orientation
      indicated that the shorter 2-ethylhexyl groups on the SI core promote tight pi-pi
      stacking of the molecular backbone, whereas n-octyl groups on the SI core hinder
      close pi-pi stacking to some degree. Conversely, the longer linear n-octyl groups
      on the DPP arms facilitate close intermolecular packing via octyl-octyl
      interdigitation. Quantum mechanics/molecular mechanics molecular dynamics
      simulations determined the optimal three-dimensional positions of the flexible
      alkyl side chains of the SI and DPP units, which elucidates the structural cause
      of the molecular packing and orientation explicitly. The alkyl-chain-dependent
      molecular stacking significantly affected the electrical properties of the
      molecular films. The edge-on oriented molecules showed high hole mobilities in
      organic field-effect transistors, while the radially oriented molecules exhibited
      high photovoltaic properties in organic photovoltaic cells. These results
      demonstrate that appropriate positioning of alkyl side chains can modulate
      crystallinity and molecular orientation in SIDPP films, which ultimately have a
      profound impact on carrier transport and photovoltaic performance. 

PMID- 24861724
TI  - Magnetic resonance imaging observations in primary central nervous system
      lymphoma.

PMID- 24861725
TI  - Mapping bone cell distributions to assess ontogenetic origin of primate midfacial
      form.
AB  - Midfacial reduction in primates has been explained as a byproduct of other growth
      patterns, especially the convergent orbits. This is at once an evolutionary and
      developmental explanation for relatively short snouts in most modern primates.
      Here, we use histological sections of perinatal nonhuman primates (tamarin,
      tarsier, loris) to investigate how orbital morphology emerges during ontogeny in
      selected primates compared to another euarchontan (Tupaia glis). We annotated
      serial histological sections for location of osteoclasts or osteoblasts, and used
      these to create three-dimensional "modeling maps" showing perinatal growth
      patterns of the facial skeleton. In addition, in one specimen we transferred
      annotations from histological sections to CT slices, to create a rotatable 3D
      volume that shows orbital modeling. Our findings suggest that growth in the
      competing orbital and neurocranial functional matrices differs among species,
      influencing modeling patterns. Distinctions among species are observed in the
      frontal bone, at a shared interface between the endocranial fossa and the orbit.
      The medial orbital wall is extensively resorptive in primates, whereas the medial
      orbit is generally depositional in Tupaia. As hypothesized, the orbital soft
      tissues encroach on available interorbital space. However, eye size cannot, by
      itself, explain the extent of reduction of the olfactory recess. In Loris, the
      posterior portion of medial orbit differed from the other primates. It showed
      evidence of outward drift where the olfactory bulb increased in cross-sectional
      area. We suggest the olfactory bulbs are significant to orbit position in
      strepsirrhines, influencing an expanded interorbital breadth at early stages of
      development.

PMID- 24861726
TI  - Visit-to-visit blood pressure variability as a prognostic marker in patients with
      cardiovascular and cerebrovascular diseases--relationships and comparisons with
      vascular markers of atherosclerosis.
AB  - BACKGROUND: Visit-to-visit blood pressure variability (BPV) is a simple surrogate
      marker for the development of atherosclerotic diseases, cardiovascular and all
      cause mortality. Nevertheless, the relative prognostic value of BPV in comparison
      with other established vascular assessments remain uncertain. METHODS: We
      prospectively followed-up 656 high-risk patients with diabetes or established
      cardiovascular or cerebrovascular diseases for the occurrence of major adverse
      cardiovascular events (MACEs). Baseline brachial endothelial function, carotid
      intima-media thickness (IMT) and plaque burden, ankle-brachial index and arterial
      stiffness were determined. Visit-to-visit BPV were recorded during a mean 18 +/-
      9 outpatient clinic visits. RESULTS: After a mean 81 +/- 12 month's follow-up,
      123 patients (19%) developed MACEs. Patients who developed a MACE had
      significantly higher systolic BPV, more severe endothelial function, arterial
      stiffness and systemic atherosclerotic burden compared to patients who did not
      develop a MACE (all P<0.01). BPV significantly correlated with all of the
      vascular assessments (P<0.01). A high carotid IMT had the greatest prognostic
      value in predicting development of a MACE (area under receiver operating
      characteristic curve (AUC) 0.69 +/- 0.03, P<0.01). A high BPV also had moderate
      prognostic value in prediction of MACE (AUC 0.65 +/- 0.03, P<0.01). After
      adjustment of confounding factors, a high BPV remained a significant independent
      predictor of MACE (hazards ratio 1.67, 95% confidence interval 1.14-2.43,
      P<0.01). CONCLUSIONS: Compared with established surrogate markers of
      atherosclerosis, visit-to-visit BPV provides similar prognostic information and
      may represent a new and simple marker for adverse outcomes in patients with
      vascular diseases.

PMID- 24861727
TI  - New insights for matrix Gla protein, vascular calcification and cardiovascular
      risk and outcome.

PMID- 24861728
TI  - Cardio-ankle vascular index (CAVI) correlates with aortic stiffness in the
      thoracic aorta using ECG-gated multi-detector row computed tomography.
AB  - BACKGROUND: The cardio-ankle vascular index (CAVI) is an arterial stiffness index
      based on the stiffness parameter beta, which is essentially independent of blood
      pressure. The objective of this study was to determine whether CAVI correlates
      with the regional stiffness parameter beta and pulse wave velocity (PWV) in the
      thoracic aorta calculated from ECG-gated multi-detector row computed tomography
      (MDCT). METHODS AND RESULTS: Forty-nine patients who underwent coronary MDCT for
      suspicious coronary artery disease were recruited. The largest and smallest
      vessel luminal cross-sectional areas of the thoracic aorta were measured from
      MDCT images to calculate PWV and stiffness parameter beta of the ascending and
      descending aorta. CAVI was also measured by VaSera VS-1000. In univariate
      analysis, CAVI significantly correlated with regional stiffness parameter beta
      and PWV, which was influenced by the inevitable part of the aging process in the
      ascending (r = 0.485, P < 0.001; r = 0.483, P < 0.001) and descending aortas (r =
      0.304, P = 0.034; r = 0.327, P = 0.022), respectively. The regional stiffness
      parameter beta did not correlate with systolic blood pressure (SBP), although the
      PWV correlated with SBP. In multivariate analysis, CAVI independently correlated
      with the stiffness parameter beta, but not with the PWV. CONCLUSION: These data
      suggest that CAVI, which correlated with stiffness parameter beta in the thoracic
      aorta, has a potential role in evaluating integrated arterial stiffness including
      that of the central aorta.

PMID- 24861729
TI  - Expression of the oncoprotein gankyrin and phosphorylated retinoblastoma protein
      in human testis and testicular germ cell tumor.
AB  - OBJECTIVE: The oncoprotein, gankyrin, is known to facilitate cell proliferation
      through phosphorylation and degradation of retinoblastoma protein. In the present
      study, we evaluated the expression of gankyrin and phosphorylated retinoblastoma
      protein in human testis and testicular germ cell tumors. METHODS: The effects of
      suppression of gankyrin by locked nucleic acid on phosphorylation status of
      retinoblastoma and cell proliferation were analyzed using western blot analysis
      and testicular tumor cell line NEC8. The expressions of gankyrin, retinoblastoma
      and retinoblastoma protein were analyzed in 93 testicular germ cell tumor samples
      and five normal human testis by immunohistochemistry. The retinoblastoma protein
      expression was determined using an antibody to retinoblastoma protein, Ser795.
      RESULTS: Gankyrin was expressed in NEC8 cells as well as a normal human testis
      and testicular tumors. Suppression of gankyrin by locked nucleic acid led to
      suppression of retinoblastoma protein and cell proliferation in NEC8 cells.
      Immunohistochemistry of normal testis showed that gankyrin is expressed
      dominantly in spermatocytes. In testicular germ cell tumors, high expressions of
      gankyrin and phosphorylated-retinoblastoma protein were observed in seminoma and
      embryonal carcinoma, whereas the expressions of both proteins were weak in
      histological subtypes of non-seminoma. Growing teratoma and testicular malignant
      transformation tissues expressed phosphorylated-retinoblastoma protein strongly,
      but gankyrin faintly. CONCLUSION: Gankyrin is dominantly expressed in normal
      spermatocytes and seminoma/embryonal carcinoma, and its expression correlates
      well with retinoblastoma protein expression except in the growing teratoma and
      testicular malignant transformation cases. These data provide new insights into
      the molecular mechanisms of normal spermatogenesis and pathogenesis of testicular
      germ cell tumors.

PMID- 24861730
TI  - The effect of acute exercise on undercarboxylated osteocalcin and insulin
      sensitivity in obese men.
AB  - Acute exercise improves insulin sensitivity for hours after the exercise is
      ceased. The skeleton contributes to glucose metabolism and insulin sensitivity
      via osteocalcin (OC) in its undercarboxylated (ucOC) form in mice. We tested the
      hypothesis that insulin sensitivity over the hours after exercise is associated
      with circulating levels of ucOC. Eleven middle-aged (58.1 +/- 2.2 years mean +/-
      SEM), obese (body mass index [BMI] = 33.1 +/- 1.4 kg/m(2) ) nondiabetic men
      completed a euglycemic-hyperinsulinemic clamp at rest (rest-control) and at 60
      minutes after exercise (4 * 4 minutes of cycling at 95% of HRpeak ). Insulin
      sensitivity was determined by glucose infusion rate relative to body mass (GIR,
      mL/kg/min) as well as GIR per unit of insulin (M-value). Blood samples and five
      muscle biopsies were obtained; two at the resting-control session, one before and
      one after clamping, and three in the exercise session, at rest, 60 minutes after
      exercise, and after the clamp. Exercise increased serum ucOC (6.4 +/- 2.1%, p =
      0.013) but not total OC (p > 0.05). Blood glucose was ~6% lower and insulin
      sensitivity was ~35% higher after exercise compared with control (both p < 0.05).
      Phosphorylated (P)-AKT (Ak thymoma) was higher after exercise and insulin
      compared with exercise alone (no insulin) and insulin alone (no exercise, all p <
      0.05). In a multiple-linear regression including BMI, age, and aerobic fitness,
      ucOC was associated with whole-body insulin sensitivity at rest (beta = 0.59, p =
      0.023) and after exercise (beta = 0.66, p = 0.005). Insulin sensitivity, after
      acute exercise, is associated with circulating levels of ucOC in obese men.
      Whether ucOC has a direct effect on skeletal muscle insulin sensitivity after
      exercise is yet to be determined.

PMID- 24861734
TI  - Magnetic susceptibility and heat capacity measurements of single crystal TbMnO3.
AB  - Measurements of the magnetic susceptibility chi and heat capacity C on single
      crystals of the multiferroic TbMnO3 are presented. A non-magnetic isostructural
      compound, LaGaO3, was used to isolate the magnetic component of the heat
      capacity. An anisotropic magnetic susceptibility, deviations from Curie-Weiss
      behaviour and a significant magnetic entropy above the antiferromagnetic ordering
      temperature TN1 = 41 K are attributed to a combination of crystal-field effects
      and short-range order between the Mn moments. Heat capacity in a magnetic field
      applied along the a axis confirms the saturation of Tb(3+) moments in 90 kOe. A
      hyperfine contribution from the Tb and Mn nuclear moments that may be convolved
      with a contribution from low-lying Tb crystal-field levels leads to a low
      temperature rise in C(T)/T. 

PMID- 24861733
TI  - The Broad Complex isoform 2 (BrC-Z2) transcriptional factor plays a critical role
      in vitellogenin transcription in the silkworm Bombyx mori.
AB  - BACKGROUND: Vitellogenin (Vg) is synthesized in the fat body of the female
      silkworm Bombyx mori and transported to the oocyte as a source of nutrition for
      embryo development. It is well known that ecdysone regulates physiological,
      developmental and behavioral events in silkworm. However, it is still not clear
      how the ecdysone regulates B. mori Vg (BmVg) transcription. METHODS:
      Electrophoretic mobility shift assay (EMSA) and cell transfection assay were used
      to reveal whether BmBrC-Z2 is involved in regulating BmVg transcription. RNAi was
      employed to illustrate the function of BmBrC-Z2 in the silkworm egg formation and
      development. RESULTS: (1) The transcription of BmVg can be induced by ecdysone in
      the female fat body. (2) Three putative BrC-Z2 cis-response elements were mapped
      to regions flanking the BmVg gene. (3) BmBrC-Z2 required direct binding to the
      cis-response elements on the BmVg promoter. (4) Over-expression of three BmBrC
      isoforms in the cell line showed that only BmBrC-Z2 could induce the BmVg
      promoter activity. (5) RNA interference (RNAi) of BmBrC-Z2 in female remarkably
      reduced BmVg synthesis and led to destructive affection on egg formation. The
      dsRNA of BmBrC-Z2 treated moths laid fewer and whiter eggs compared to the
      control. CONCLUSIONS: BmBrC-Z2 transported the ecdysone signal then regulated
      BmVg transcription directly to control vitellogenesis and egg formation in the
      silkworm. GENERAL SIGNIFICANCE: The results of this study revealed that BmBrC-Z2
      as a key factor to mediate ecdysone regulates reproduction in the silkworm.

PMID- 24861732
TI  - Adherence to treatment in a Western European paediatric population with
      haemophilia: reliability and validity of the VERITAS-Pro scale.
AB  - Treatment adherence in haemophilia is strongly associated with quality of life
      and the cost-benefit of treatment. Therefore, it is important to quantify and
      monitor it. This study aimed to validate a translation of the VERITAS-Pro cross
      culturally and analyse treatment adherence in a Dutch population of paediatric
      haemophilia patients. Children aged 1-18 years with haemophilia were included
      from three Haemophilia Treatment Centres, on prophylactic clotting factor
      replacement therapy for more than 1 year. Parents and adolescents were analysed
      separately. The adherence scale for prophylactic therapy (VERITAS-Pro) was
      translated according to international guidelines. This instrument contains a
      total of six subscales ('Time', 'Dose', 'Plan', 'Remember', 'Skip' and
      'Communicate') each with four items. Lower scores reflect higher adherence.
      Overall response rate was 85%, leading to a study population of 60 children. Mean
      age was 10 years (SD 4.1). Internal consistency reliability: Mean Cronbach's
      alphas were adequate (>0.70) for total score and the subscales 'Skip' and
      'Communicate'. Item-own subscale correlations were stronger than most item-other
      subscale correlations. Convergent validity: Total scores were higher for non
      adherent participants compared with adherent participants according to patient
      infusion logs (n = 48; P < 0.05). Test-retest correlations: Significant for all
      scales except 'Dose' (n = 58; P < 0.01). This study demonstrates applicability of
      VERITAS-Pro outside the United States, as total score and most subscales
      effectively quantified treatment adherence in a Dutch paediatric population on
      prophylactic therapy. Non-adherent respondents' total scores were significantly
      higher, demonstrating the ability of VERITAS-Pro to identify non-adherent
      individuals. 

PMID- 24861731
TI  - Persistent neutrophil dysfunction and suppression of acute lung injury in mice
      following cecal ligation and puncture sepsis.
AB  - Sepsis, both in humans and in rodents, is associated with persistent
      immunosuppression accompanied by defects in innate immunity during the acute
      phase of sepsis. Mice were rendered septic by cecal ligation and puncture (CLP)
      followed by the induction of acute lung injury, employing distal airway
      deposition of IgG immune complexes, in order to quantitatively evaluate innate
      immune responses following the induction of sepsis. Suppression of innate immune
      responses in the lung occurred as early as 12 h after CLP and up to 21 days
      thereafter. The mechanism of innate immune defects included a reduced leak of
      albumin into the lungs together with reduced levels of tumor necrosis factor in
      bronchoalveolar lavage fluids and increased levels of interleukin-10 that were
      persistent. Bone marrow-derived neutrophils (polymorphonuclear neutrophils; PMNs)
      from CLP mice also had reduced levels of the activation marker CD11b and a
      depressed respiratory burst following stimulation in vitro. These results were
      not observed in mice with endotoxemia, where the innate inflammatory response was
      preserved. However, sustained lymphopenia was present in both models, suggesting
      differential regulation of innate and adaptive immunity in the two sepsis models.
      These data indicate that CLP induced a prolonged suppression of inflammatory
      responses both in the lung and systemically, as defined by bone marrow-derived
      PMN dysfunction.

PMID- 24861735
TI  - A dedication to Chang Kee Lim.

PMID- 24861736
TI  - Reminiscences of Chang Kee Lim.

PMID- 24861738
TI  - Analysis of 10 systemic pesticide residues in various baby foods using liquid
      chromatography-tandem mass spectrometry.
AB  - Ten systemic pesticides, comprising methomyl, thiamethoxam, acetamiprid,
      carbofuran, fosthiazate, metalaxyl, azoxystrobin, diethofencarb, propiconazole,
      and difenoconazole, were detected in 13 baby foods (cereals, boiled potatoes,
      fruit and milk) using QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe)
      for sample preparation and liquid chromatography tandem mass spectrometry for
      analysis. The matrix-matched calibration curves showed good linearity with
      determination coefficients (R(2) ) >0.992. The limits of detection and
      quantitation were 0.0015-0.003 and 0.005-0.01 mg/kg, respectively. The mean
      recoveries of three different concentrations ranged from 69.2 to 127.1% with
      relative standard deviations <20%. The method was successfully applied to 13
      actual samples collected from a local market, and none of the samples were found
      to contain pesticide residues. This method is suitable for the identification and
      quantification of systemic pesticides with matrix-matched standards in various
      baby foods.

PMID- 24861737
TI  - Biological and chemical standardization of a hop (Humulus lupulus) botanical
      dietary supplement.
AB  - Concerned about the safety of conventional estrogen replacement therapy, women
      are using botanical dietary supplements as alternatives for the management of
      menopausal symptoms such as hot flashes. Before botanical dietary supplements can
      be evaluated clinically for safety and efficacy, botanically authenticated and
      standardized forms are required. To address the demand for a standardized,
      estrogenic botanical dietary supplement, an extract of hops (Humulus lupulus L.)
      was developed. Although valued in the brewing of beer, hop extracts are used as
      anxiolytics and hypnotics and have well-established estrogenic constituents.
      Starting with a hop cultivar used in the brewing industry, spent hops (the
      residue remaining after extraction of bitter acids) were formulated into a
      botanical dietary supplement that was then chemically and biologically
      standardized. Biological standardization utilized the estrogen-dependent
      induction of alkaline phosphatase in the Ishikawa cell line. Chemical
      standardization was based on the prenylated phenols in hops that included
      estrogenic 8-prenylnaringenin, its isomer 6-prenylnaringenin, and pro-estrogenic
      isoxanthohumol and its isomeric chalcone xanthohumol, all of which were measured
      using high-performance liquid chromatography-tandem mass spectrometry. The
      product of this process was a reproducible botanical extract suitable for
      subsequent investigations of safety and efficacy.

PMID- 24861739
TI  - Comprehensive and temporal analysis of secreted proteins in the medium from IL-6
      exposed human hepatocyte.
AB  - We have previously identified intracellular secretory acute phase response (sAPR)
      proteins in human hepatocytes following interleukin-6 (IL-6) induction by
      fluorogenic derivatization (FD)-liquid chromatography (LC)-tandem mass
      spectrometry (MS/MS). In this report, we utilized this method, which uses 7
      chloro-N-[2-(dimethylamino)ethyl]-2,1,3-benzoxadiazole-4-sulfonamide (DAABD-Cl)
      as the FD reagent, to comprehensively and time-dependently analyze secreted
      proteins in the medium, including sAPR proteins. Since DAABD-Cl selectively
      reacts with thiol moieties of cysteinyl residues, direct derivatization, high
      resolution LC separation and identification of the secreted proteins in the
      culture medium were successfully achieved without a pretreatment step. As a
      result, 14 sAPR proteins were identified simultaneously during a 72 h induction
      by IL-6. The secretion levels of 11 proteins increased, whereas the secretion
      levels of three important transport proteins decreased (albumin, retinol-binding
      protein 4 and transthyretin). In addition, the secretion level of a haptoglobin
      was found to increase significantly between 0 and 6 h by 1.88-fold compared with
      the control sample. The secretion levels of four cytoplasmic proteins increased:
      LDH, a known marker for cell damage, and GSTA1, FABP1 and ADH1B, which are marker
      proteins for hepatocellular damage. The secretion levels of the other two newly
      identified cytoplasmic proteins, profilin-1 and SOD2, were also found to
      increase, suggesting that these two proteins represent novel markers for cell
      damage. These results suggest that the FD-LC-MS/MS proteomics method can be used
      to analyze comprehensively and time-dependently the secreted proteins and thereby
      can offer information that aids our understanding of the dynamics of protein
      secretion affected by the exposure of cytokines such as IL-6.

PMID- 24861740
TI  - Determination of anxiolytic veterinary drugs from biological fertilizer blood
      meal using liquid chromatography high-resolution mass spectrometry.
AB  - A liquid environment-friendly agricultural material originating from animal
      blood, blood meal, was employed to detect anxiolytic veterinary drugs using a
      combination of liquid-liquid extraction (LLE) and positive electrospray
      ionization Orbitrap mass spectrometry. Every positive ion of the analytes was
      consistent with [M+H](+) , and the accurate mass analysis and mass spectral
      filtration with a 2-ppm mass tolerance window were applied to identify and
      quantitate the analytes and metabolites. The developed LLE method was validated
      with the lowest calibrated level, linearity (r(2) ), recovery, repeatability and
      the within-laboratory reproducibility, which were in the ranges of 0.3-1 ug/L,
      0.9963-0.9995, 48.3-117.5%, 1.1-12.6% and 2.3-15.7%, respectively. The LLE method
      was compared with a solid-phase extraction (SPE) method; however, its recoveries
      were <70% for most of the analytes despite good repeatability of 1.2-7.4%. The
      analytes and the ascertained acepromazine, azaperone and xylazine metabolites
      were monitored in four actual liquid blood meal samples, and none of the targeted
      compounds were observed.

PMID- 24861741
TI  - Recent advances in development and application of derivatization reagents having
      a benzofurazan structure: a brief overview.
AB  - Chemical derivatization is often used to improve the separation efficiency and to
      enhance the detectability of the target compounds in high-performance liquid
      chromatography and capillary electrophoresis. The derivatization reagents having
      a benzofurazan (2,1,3-benzoxadiazole) structure are one of the most often used
      reagent for this purpose. In this paper, the recent advances in the development
      and the application of benzofurazan derivatization reagents are reviewed.

PMID- 24861742
TI  - Analysis of etoxazole in red pepper after major modification of QuEChERS for gas
      chromatography-nitrogen phosphorus detection.
AB  - A major modification to the QuEChERS (quick, easy, cheap, effective, rugged and
      safe) method was developed for the analysis of etoxazole in red pepper using gas
      chromatography coupled with a nitrogen-phosphorus detector. Etoxazole was
      extracted with acetonitrile, partitioned with magnesium sulfate and purified with
      a solid-phase extraction cartridge. The method showed good linearity with a
      determination coefficient (R(2) ) of 0.998 for the 0.02-2.0 mg/L concentration
      range. The method was validated using blank red pepper spiked at 0.2 and 1.0
      mg/kg, and the average recovery rate was 74.4-79.1% with relative standard
      deviations <5% for intra- and inter-day precision. The limits of detection and
      quantification were 0.007 and 0.02 mg/kg, respectively. The developed method was
      successfully applied to field-incurred samples, and the presence of etoxazole
      residues was confirmed using gas chromatography/mass spectrometry.

PMID- 24861743
TI  - Optimization of supercritical fluid extraction method for detection of
      fluquinconazole and tetraconazole in soil using gas chromatography and
      confirmation using GC-MS: application to dissipation kinetics.
AB  - The aim of this study was to establish an analytical method to detect
      fluquinconazole and tetraconazole in soil using supercritical fluid extraction
      (SFE) and gas chromatography (GC). The optimal extraction conditions for SFE
      were: temperature, 60  degrees C; pressure, 280 kg/cm(2) ; extraction time, 50
      min; and a 10% modifier ratio. The linearity of the calibration curves was good
      and yielded a determination coefficient (R(2) ) >= 0.995. The soil samples were
      fortified with known quantities of the analytes at three different concentrations
      (0.01, 0.02 and 0.1 ug/g for fluquinconazole; 0.05, 0.1 and 0.5 ug/g for
      tetraconazole), and the recoveries ranged between 83.7 and 94.1%. The intra- and
      inter-day relative standard deviations were 1.3-10.6 and 2.2-11.9% for
      fluquinconazole and tetraconazole, respectively. The limit of detection and limit
      of quantitation were 0.002 and 0.01 ug/g for fluquinconazole and 0.01 and 0.05
      for tetraconazole, respectively. The method was successfully applied to the
      analysis of soil residues collected from an onion field. The results show that a
      combination of SFE and GC can be used as an environmentally friendly technique to
      detect fungicides in soil.

PMID- 24861744
TI  - Analysis and pharmacokinetic study of curdione in Rhizoma Curcumae by
      UPLC/QTOF/MS.
AB  - An ultra-performance liquid chromatography-quadrupole time-of-flight/mass
      spectrometry (UPLC/QTOF/MS) method was established to determine the chemical
      components of curcuma rhizomes (Ezhu) and their pharmacokinetics. Chromatographic
      separation was performed by UPLC using a 1.8 um column in order to obtain good
      resolution and increase the sensitivity of analysis. Accurate mass measurement
      within 5 ppm error for each ion produced in positive mode electrospray ionization
      and the subsequent QTOF product ions enabled 12 compounds to be identified.
      Several of the identified components, including beta-elemene, curcumol,
      germacrone and curdione, are thought to be the biologically active ingredients.
      Quantitative pharmacokinetic analysis was also carried out by UPLC/QTOF/MS. Using
      20(S)-protopanoxadiol as an internal standard, samples were prepared by protein
      precipitation with methanol. Chromatographic separation was performed on an
      Agilent Extend-C18 column (2.1 * 50 mm, 1.8 um) with acetonitrile (0.1% formic
      acid)-water (0.1% formic acid) for gradient elution. Curdione calibration plots
      were linear over the range of 0.1-12.2 ug/mL for curdione in plasma with the
      lower quantification limit being 6.5 ng/mL, and the recovery from plasma was
      about 105.2%. The RSD for both intra- and inter-day precision was <9.9%.

PMID- 24861745
TI  - Liquid chromatography electrospray ionization tandem mass spectrometry study of
      nilutamide and its stress degradation products: in silico toxicity prediction of
      degradation products.
AB  - Nilutamide, a nonsteroidal anti-androgen drug, widely used in the treatment of
      prostate cancer, was subjected to hydrolytic, photolytic, thermal and oxidative
      stress conditions as per International Conference on Harmonization guidelines Q1A
      (R2). Nilutamide showed significant degradation under basic hydrolysis and
      photolytic stress conditions, while it was stable to neutral, acidic and thermal
      stress conditions. Five degradation products were formed and the chromatographic
      separation of nilutamide and its degradation products was achieved on a Waters
      C18 column (4.6 * 250 mm, 5 um) using a mobile phase consisting of acetonitrile
      and 0.1% of formic acid in an isocratic elution method. All these degradation
      products were characterized by LC/MS/MS in negative ion mode, combined with
      accurate mass measurements. To assign likely structures for the observed
      degradation products, the fragmentation patterns of the deprotonated drug and its
      degradation products were compared. The in silico toxicity of the drug and its
      degradation products was also assessed using TOPKAT software. The carcinogenicity
      probability of the degradation products, DP-I-IV, was greater than that of
      nilutamide.

PMID- 24861746
TI  - Quantitation of P450 3A4 endogenous biomarker - 4beta-hydroxycholesterol - in
      human plasma using LC/ESI-MS/MS.
AB  - 4beta-Hydroxycholesterol (4beta-HC) has been proposed as a new endogenous
      biomarker for cytochrome P450 3A4/5 activity. Therefore, it is important to have
      a robust method for its accurate determination in human plasma. Here a liquid
      chromatography-tandem mass spectrometry with electrospray ionization (LC/ESI
      MS/MS) assay for the quantitation of 4beta-HC in human plasma is described. While
      the calibration standards were prepared in a surrogate matrix for human plasma,
      the quality control samples were prepared in human plasma to mimic the incurred
      study samples. In order to achieve accurate determination of 4beta-HC, the
      chromatographic separation of 4beta-HC from its isomers, especially 4alpha
      hydroxycholesterol (4alpha-HC), was crucial. In the absence of an authentic
      4alpha-HC standard at the time of this study, an alternative selectivity test
      strategy was developed to confirm the separation. After being alkalized with
      potassium hydroxide, the human plasma sample (50 MUL) was extracted with hexane,
      derivatized into picolinyl esters using picolinic acid, extracted again with
      hexane, and then analyzed by LC/ESI-MS/MS. The calibration curve range was 5-500
      ng/mL and the chromatographic separation was achieved on a 50 * 2.1 mm Thermal
      Hypersil Gold column with a gradient elution. The assay accuracy, precision,
      linearity, selectivity and analyte stability throughout the analysis were
      established. The validated assay was successfully applied to a Phase I clinical
      study for the measurement of 4beta-HC in human plasma.

PMID- 24861747
TI  - Development and validation of UHPLC method for the determination of cyclosporine
      A in biological samples.
AB  - The aim of the study was to develop and validate a simple and rapid method for
      the determination of cyclosporine A (CsA) in ocular rabbit tissues using reversed
      phase ultra-high-performance liquid chromatography (UHPLC) with UV detection.
      Previous publications on chromatographic methods of CsA determination in ocular
      tissues involved only reversed-phase HPLC separation, usually in combination with
      such detection techniques as radio-immunoassay and mass spectrometry. The
      application of the UHPLC technique allowed us to significantly decrease the
      analysis time. Cyclosporine D (CsD) was applied as the internal standard.
      Satisfactory separation was achieved on an XB-C18 Kinetex column at 60 degrees C
      with the use of gradient elution mode. The retention times of CsA and CsD were
      found to be 4.5 and 5.1 min, respectively. The developed assay is specific,
      sensitive (limit of detection = 6 ng/mL and limit of quantitation = 18 ng/mL) and
      linear within the analyte concentration range of 0.018-5 ug/mL, with a
      correlation coefficient of 0.999. High sensitivity, low injection volume (10
      MUL), short time of analysis (6.5 min) and simplicity make this method useful for
      the fast analysis of CsA in rabbit ocular tissues and fluids: lacrimal fluid,
      aqueous humor, cornea, conjunctiva and eye globe.

PMID- 24861748
TI  - Quantitation of sulfur-containing amino acids, homocysteine, methionine and
      cysteine in dried blood spot from newborn baby by HPLC-fluorescence detection.
AB  - Sulfur-containing amino acids (SAAs), homocysteine (Hcy), methionine (Met) and
      cysteine (Cys) in blood are related to homocystinuria, an inborn error of
      metabolism. In this study, an assay method with HPLC-fluorescence detection to
      quantify the SAAs in a dried blood spot was established and applied to samples
      from newborn babies (n=200). Sample pretreatment involving reduction,
      derivatization with 4-(N,N-dimethylaminosulfonyl)-7-fluoro-2,1,3-benzoxadiazole,
      and liquid-liquid extraction with ethyl acetate gave the separation of the
      derivatives with retention times within 12 min. The method was enough sensitive
      to determine the SAAs in a dried blood spot with 0.04-0.14 um as the limit of
      detection at a signal-to-noise ratio of 3. However, the absolute recoveries were
      very low (5.7% for Hcy, 4.6% for Cys) except for Met (105.4%) owing to
      inefficient recovery of Hcy and Cys from the blood matrix. Other validation
      parameters such as accuracy (93.5-106.2%) and intra- (<= 9.0%) and inter-day
      precisions (<= 8.7%) were acceptable. The reliability of a dried blood spot as an
      analytical sample was estimated. Furthermore, the proposed method was
      successfully applied to dried blood spots prepared from newborn babies.

PMID- 24861749
TI  - Liquid chromatographic enantioseparation of (RS)-mexiletine and (RS)-fluoxetine
      using chiral derivatizing reagents synthesized with (S)-naproxen moiety.
AB  - Enantiomeric separation of racemic mexiletine and fluoxetine was achieved using
      three chiral derivatizing reagents (CDRs) based on (S)-naproxen. Diastereomers
      were synthesized by reaction of mexiletine or fluoxetine with the CDRs and were
      separated on a C18 column under reversed-phase conditions using a binary mixture
      of acetonitrile and triethylammonium phosphate/water, with UV detection at 230
      and 226 nm. The results obtained for enantioseparation of the two drugs using the
      three CDRs were compiled and compared. The conditions for derivatization and
      chromatographic separation were optimized. The method was validated for
      linearity, repeatability, limit of detection and limit of quantification.

PMID- 24861750
TI  - Development of HPLC-UV method for rapid and sensitive analysis of topically
      applied tetracaine: its comparison with a CZE method.
AB  - Topically applied tetracaine is a local anaesthetic. A novel HPLC method for the
      rapid and sensitive analysis of tetracaine was developed and compared with a
      short end direction capillary zone electrophoresis (CZE) method. The method was
      developed and validated for the separation and quantification of tetracaine in
      skin samples removed by 'tape-stripping'. Tetracaine was extracted from tape with
      100% methanol, which was then diluted to 50% with water for injection. Tetracaine
      and the internal standard, procaine, were separated on a reversed-phase Luna
      PFP(2), 3 um, 150 * 4.6 mm column at ambient temperature using isocratic elution
      with KH2 PO4 buffer (pH 2.5) and methanol (35:65, v/v). The flow rate was 1
      mL/min, with detection at 312 nm. The limit of quantification for tetracaine was
      0.03 ug/mL. Calibration lines were linear with r(2) values >0.99. The within- and
      between-assay imprecision and the percentage of inaccuracy for the QC samples
      including lower and upper limits of quantitation were <6 and <10%. The absolute
      mean recovery of tetracaine was >92%. Compared with CZE, the mean percentage
      error and the absolute mean percentage error were 0.62 and 6.29, respectively.
      The two methods were compared in a number of pharmacokinetic studies.

PMID- 24861751
TI  - UPLC/ESI-MS/MS-based determination of metabolism of several new illicit drugs,
      ADB-FUBINACA, AB-FUBINACA, AB-PINACA, QUPIC, 5F-QUPIC and alpha-PVT, by human
      liver microsome.
AB  - The metabolism by human liver microsomes of several new illicit drugs, that is, N
      (1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1-(4-fluorobenzyl)-1H-indazole-3-
      carboxamide (ADB-FUBINACA), N-(1-amino-3-methyl-1-oxobutan-2-yl)-1- (4
      fluorobenzyl)-1H-indazole-3-carboxamide (AB-FUBINACA), N-(1-amino-3-methyl-1
      oxobutan-2-yl)-1-pentyl-1H-indazole-3-carboxamide (AB-PINACA), quinolin-8-yl 1
      pentyl-(1H-indole)-3-carboxylate (QUPIC), quinolin-8-yl 1-(5-fluoropentyl)-(1H
      indole)-3-carboxylate (5 F-QUPIC) and alpha-pyrrolidinovalerothiophenone (alpha
      PVT), which have indole, indazole, quinolinol ester and thiophene structures, was
      investigated using reversed-phase chromatography and mass spectrometry. The
      present method is based upon the oxidation by cytochrome p450 superfamily enzymes
      in the microsomes. The oxidation of ADB-FUBINACA and AB-FUBINACA mainly occurred
      on the N-(1-amino-alkyl-1-oxobutan) moiety. However, the oxidation of AB-PINACA
      seemed to occur on the 1-pentyl moiety. On the other hand, QUPIC and 5 F-QUPIC,
      which have a quinolinol ester structure, predominantly underwent a cleavage
      reaction to produce indoleacetic acid type metabolites. In contrast, the
      metabolism reaction of alpha-PVT was different from that of the other tested
      drugs, and various oxidation products were observed on the chromatograms. The
      obtained metabolites are not in conflict with the results predicted by MetaboLynx
      software. However, the exact structures of the metabolites, except for 1-pentyl
      1H-indole-3-carboxylic acid (QUPIC metabolite) and 1-(5-fluoropentyl)-1H-indole-3
      carboxylic acid (5 F-QUPIC metabolite), are currently not proven, because we have
      no authentic compounds for comparison. The proposed approach using human liver
      microsome seems to provide a new technology for the prediction of possible
      metabolites occuring in humans.

PMID- 24861752
TI  - Microextraction by packed sorbent: an emerging, selective and high-throughput
      extraction technique in bioanalysis.
AB  - Sample preparation is an important analytical step regarding the isolation and
      concentration of desired components from complex matrices and greatly influences
      their reliable and accurate analysis and data quality. It is the most labor
      intensive and error-prone process in analytical methodology and, therefore, may
      influence the analytical performance of the target analytes quantification. Many
      conventional sample preparation methods are relatively complicated, involving
      time-consuming procedures and requiring large volumes of organic solvents. Recent
      trends in sample preparation include miniaturization, automation, high-throughput
      performance, on-line coupling with analytical instruments and low-cost operation
      through extremely low volume or no solvent consumption. Micro-extraction
      techniques, such as micro-extraction by packed sorbent (MEPS), have these
      advantages over the traditional techniques. This paper gives an overview of MEPS
      technique, including the role of sample preparation in bioanalysis, the MEPS
      description namely MEPS formats (on- and off-line), sorbents, experimental and
      protocols, factors that affect the MEPS performance, and the major advantages and
      limitations of MEPS compared with other sample preparation techniques. We also
      summarize MEPS recent applications in bioanalysis.

PMID- 24861753
TI  - Recent advances in proteomics: towards the human proteome.
AB  - After the successful completion of the Human Genome project in 2003, the next
      major challenge was to understand when and where the encoded proteins were
      expressed, and to generate a map of the complex, interconnected pathways,
      networks and molecular systems (the human proteome) that, taken together, control
      the workings of all cells, tissues, organs and organisms. Proteomics will be
      fundamental for such studies. This review summarizes the key discoveries that
      laid down the foundations for proteomics as we now know it, and describes key
      recent technological advances that will undoubtedly contribute to achieving the
      initial goal of the Human Proteome Organization of identifying and characterizing
      at least one protein product and representative post-translational modifications,
      single amino acid polymorphisms and splice variant isoforms from the 20,300 human
      protein-coding genes within the next 10 years. Successful unraveling of the human
      proteome will undoubtedly improve our understanding of human biology at the
      cellular level and lay the foundations for improved diagnostic, prognostic,
      therapeutic and preventive medical outcomes as we enter the era of personalized
      medicine.

PMID- 24861754
TI  - Determination of 4-hydroxy-2-nonenal in serum by high-performance liquid
      chromatography with fluorescence detection after pre-column derivatization using
      4-(N,N-dimethylaminosulfonyl)-7-hydrazino-2, 1,3-benzoxadiazole.
AB  - 4-Hydroxy-2-nonenal (4HNE) is a major aldehyde generated during lipid
      peroxidation. The clinical monitoring of 4HNE in biological fluids should be
      useful for the early diagnosis of several diseases involving lipid peroxidation,
      such as rheumatoid arthritis, Parkinson's disease and cancer. In this study, an
      HPLC with fluorescence detection method was developed for the determination of
      4HNE in human serum. The proposed method involves the extraction of 4HNE from
      human serum by sub-zero temperature extraction and fluorescent labeling of 4HNE
      with 4-(N,N-dimethylaminosulfonyl)-7-hydrazino-2, 1,3-benzoxadiazole. The lower
      detection limit (signal-to-noise ratio = 3) of the method was 0.06 MUm in serum.
      The proposed method was successfully applied to the measurement of 4HNE in sera
      obtained from patients with rheumatoid arthritis.

PMID- 24861755
TI  - Improved separation of fluorogenic derivatized intact proteins with high
      resolution and efficiency using a reversed-phase liquid chromatographic system.
AB  - Although the efficient separation of intact protein mixtures is extremely
      difficult, reversed-phase chromatography is an important technique for performing
      quantitative, accurate and reproducible proteomics analyses. Here, we show that,
      despite the operating constraints of conventional high-performance liquid
      chromatography, such as column temperature, operating pressure and separation
      time, comprehensive separation of fluorogenic derivatized intact proteins could
      be achieved with high resolution and separation efficiency. First, amylin was
      chosen as a model peptide and used to estimate the separation efficiency with
      respect to column temperature and flow rate, as indicated by peak capacity. Then,
      an extract of human primary hepatocytes was used to model complex component
      mixtures and the separation conditions were optimized. The effects of mobile
      phase pH, the separation time and the column length were also investigated.
      Consequently, more than 890 peaks could be separated efficiently in the extract,
      which is 1.5-fold greater than when using conventional conditions. Finally, it
      was demonstrated that both longer separation time and column length contributed
      greatly to the effective separation of the protein mixture. These results are
      expected to provide insights into the separation of intact proteins.

PMID- 24861756
TI  - Enantioseparation of meptazinol and its three intermediate enantiomers by
      capillary electrophoresis using a new cationic beta-cyclodextrin derivative in
      single and dual cyclodextrin systems.
AB  - A new cationic beta-cyclodextrin derivative, mono-6-deoxy-6-piperdine-beta
      cyclodextrin (PIP-beta-CD), was synthesized and applied as a chiral selector for
      the enantioseparation of meptazinol and its three intermediate enantiomers
      (intermediates II-IV) in capillary electrophoresis. When PIP-beta-CD was employed
      as the single CD system, intermediate II was baseline enantioseparated while the
      results for the other analytes were less satisfactory. In order to enhance the
      selectivity and resolution of meptazinol intermediate III and intermediate IV,
      dual CD systems of PIP-beta-CD in combination with three different neutral CDs
      were synthesized and tested: beta-cyclodextrin (beta-CD), trimethyl-beta
      cyclodextrin (TM-beta-CD) and hydroxypropyl-beta-cyclodextrin (HP-beta-CD). After
      investigating the effect on the enantioseparation efficiency of the nature and
      the concentration of both CDs, the dual CD system consisting of PIP-beta-CD and
      HP-beta-CD was shown to be the most efficient for the simultaneous
      enantioseparation of meptazinol intermediates III and IV.

PMID- 24861757
TI  - Dried saliva spot as a sampling technique for saliva samples.
AB  - For the first time, dried saliva spot (DSS) was used as a sampling technique for
      saliva samples. In the DSS technique 50 MUL of saliva was collected on filter
      paper and the saliva was then extracted with an organic solvent. The local
      anesthetic lidocaine was used as a model compound, which was determined in the
      DSS using liquid chromatography and mass spectrometry. The results obtained for
      the determination of lidocaine in saliva using DSS were compared with those from
      a previous study using a microextraction by packed sorbent syringe as the
      sampling method for saliva. This study shows that DSS can be used for the
      analysis of saliva samples. The method is promising and very easy in terms of
      sampling and extraction procedures. The results from this study are in good
      agreement with those from our previous work on the determination of lidocaine in
      saliva. DSS can open a new dimension in the saliva handling process in terms of
      sampling, storing and transport.

PMID- 24861758
TI  - Kidney tissue targeted metabolic profiling of glucocorticoid-induced osteoporosis
      and the proposed therapeutic effects of Rhizoma Drynariae studied using
      UHPLC/MS/MS.
AB  - Traditional Chinese medicine and modern science have indicated that there is a
      close relationship between bone and kidney. In light of this, this project was
      designed to study the metabolic profiling by UHPLC/MS/MS of glucocorticoid
      induced osteoporosis in kidney tissue and the possible therapeutic effects of
      Rhizoma Drynariae (RD), a classic traditional Chinese medicine, in improving the
      kidney function and strengthening bone. Twenty-one Wistar rats were divided into
      three groups: control group (rats before prednisolone inducing), a model group
      (prednisolone-induced group) and a treatment group (prednisolone-induced rats
      that were then administered RD ethanol extracts). By using pattern recognition
      analysis, a significant change in the metabolic profile of kidney tissue samples
      was observed in the model group and restoration of the profile was observed after
      the administration of RD ethanol extracts. Some significantly changed biomarkers
      related to osteoporosis such as sphingolipids (C16 dihydrosphingosine, C18
      dihydrosphingosine, C18 phytosphingosine, C20 phytosphingosine),
      lysophosphatidycholines (C16:0 LPC, C18:0 LPC) and phenylalanine were identified.
      As a complement to the metabolic profiling of RD in plasma, these biomarkers
      suggest that kidney damage, cell cytotoxicity and apoptosis exist in osteoporosis
      rats, which is helpful in further understanding the underlying process of
      glucocorticoid-induced osetoporosis and the suggested therapeutic effects of RD.
      The method shows that tissue target metabonomics might provide a powerful tool to
      further understand the process of disease and the mechanism of therapeutic effect
      of Chinese medicines.

PMID- 24861759
TI  - Intestinal transport of sophocarpine across the Caco-2 cell monolayer model and
      quantification by LC/MS.
AB  - Sophocarpine is a biologically active component obtained from the foxtail-like
      sophora herb and seed that is often orally administered for the treatment of
      cancer and chronic bronchial asthma. The aim of this study was to develop a rapid
      and specific LC/MS method for the determination of sophocarpine and to explore
      its transcellular transport mechanism across the Caco-2 (the human colon
      adenocarcia cell lines) monolayer cell transwell model. Caco-2 cells were seeded
      on permeable polycarbonate membranes and incubated for 21 days. Before the
      experiment, the trans-epithelial electric resistance, integrity and alkaline
      phosphatase activity of the Caco-2 monolayers were verified and used in
      subsequent experiments. In the Caco-2 model constructed, many influencing factors
      were investigated, including time, concentration, pH and different protein
      inhibitors. The results suggested that sophocarpine was transported mainly by
      passive diffusion. The flux of sophocarpine was time- and concentration
      dependent, and the pH also had an effect on its transportation. The PappBA was
      higher than PappAB , indicating that a polarized transport might exist for
      sophocarpine. MK-571 and reserpine, inhibitors of the multidrug resistance
      associated protein 2 and the breast cancer resistance protein, decreased the
      efflux of sophocarpine, while verapamil had no effect on its transport. These
      results revealed that sophocarpine is absorbed mainly by passive diffusion, and
      that a carrier-mediated mechanism is also involved in the transport of
      sophocarpine.

PMID- 24861760
TI  - Determination of 4-hydroxy-2-nonenal in serum by high-performance liquid
      chromatography with fluorescence detection after pre-column derivatization using
      4-(N,N-dimethylaminosulfonyl)-7-hydrazino-2,1,3-benzoxadiazole.
AB  - 4-Hydroxy-2-nonenal (4HNE) is a major aldehyde generated during lipid
      peroxidation. The clinical monitoring of 4HNE in biological fluids could be
      useful for the early diagnosis of several diseases involving lipid peroxidation,
      such as rheumatoid arthritis, Parkinson's disease and cancer. In this study, an
      HPLC with fluorescence detection method was developed for the determination of
      4HNE in human serum. The proposed method involves the extraction of 4HNE from
      human serum by subzero temperature extraction and fluorescent labeling of 4HNE
      with 4-(N,N-dimethylaminosulfonyl)-7-hydrazino-2,1,3-benzoxadiazole. The lower
      detection limit (signal-to-noise ratio=3) of the method was 0.06 um in serum. The
      proposed method was successfully applied to the measurement of 4HNE in sera
      obtained from patients with rheumatoid arthritis.

PMID- 24861761
TI  - A dispersive liquid-liquid microextraction method based on the solidification of
      a floating organic drop combined with HPLC for the determination of lovastatin
      and simvastatin in rat urine.
AB  - A dispersive liquid-liquid microextraction method based on solidification of
      floating organic drop combined with HPLC was developed for the determination of
      lovastatin and simvastatin in rat urine for the first time. 1-Dodecanol and
      methanol were used as the extraction and disperser solvents, respectively.
      Several important parameters influencing the micro-extraction efficiency were
      studied and systematically optimized, including the type and volume of extraction
      solvent and disperser solvent, extraction time, pH and salt concentration. The
      analytes were separated on a Kromasil C18 column at 30 degrees C with a mobile
      phase of methanol and 0.2% acetic acid in water (83:17, v/v) and detected at 238
      nm. Under the optimal conditions, the maximum number of enrichment factors for
      both analytes was 27. The linear ranges were 20.08-1004 and 20.00-1000 ug/L with
      the correlation coefficients ranging from 0.9990 to 0.9994 for lovastatin and
      simvastatin, respectively. The volume of organic solvent consumed in extraction
      was <0.3 mL, and the extraction time was 10 min. The newly developed environment
      friendly sample pretreatment method will be a good alternative to conventional
      techniques, such as solid-phase extraction, liquid-liquid extraction and protein
      precipitation, for the HPLC determination of lovastatin and simvastatin in
      biological samples.

PMID- 24861762
TI  - Determination of protein-unbound rhynchiphylline brain distribution by
      microdialysis and ultra-performance liquid chromatography with tandem mass
      spectrometry.
AB  - The stem with hook of Uncaria rhynchophylla (Chinese herbal name Gou-Teng) is a
      traditional Chinese medicine that has been ethnopharmacologically used to
      extinguish wind and clean interior heat. Rhynchophylline (RHY), a tetracyclic
      oxindole alkaloid isolated from U. rhynchophylla, displays significant
      antineuroinflammatory effects. However, there is no evidence to indicate that
      rhynchophylline can cross the blood-brain barrier and be detected in the brain.
      In this study, an in vivo microdialysis sampling method coupled with UPLC/MS/MS
      was employed for the continuous simultaneous monitoring of unbound RHY in rat
      blood and brain. The precursor ion -> product ion transition at m/z 385.2 ->
      160.0 for rhynchophylline was monitored. A calibration curve gave good linearity
      (r>0.996) over the concentration range from 0.5 to 1000 ng/mL. The results
      demonstrated that rhynchophylline could be detected in the brain and plasma from
      15 min to 6 h after its administration (1 or 10 mg/kg, i.v.). All the
      pharmacokinetic parameters of rhynchophylline in the brain and plasma were
      obtained. These results show that rhynchophylline can cross the blood-brain
      barrier and they provide useful clinical information.

PMID- 24861763
TI  - Preparation of lysozyme molecularly imprinted polymers and purification of
      lysozyme from egg white.
AB  - Molecular imprinting as a promising and facile separation technique has received
      much attention because of its high selectivity for target molecules. In this
      study, lysozyme molecularly imprinted polymers (Lys-MIPs) were successfully
      prepared by the entrapment method with lysozyme as the template molecule,
      acrylamide as the functional monomer and N,N-methylenebisacrylamide as the cross
      linker. The removal of the template lysozyme from the molecularly imprinted
      polymers was investigated in detail by two methods. The synthesized Lys-MIPs were
      characterized by scanning electron microscopy and Fourier transform-infrared, and
      the adsorption capacity, selectivity and reproducibility of the Lys-MIPs were
      also evaluated. The maximum adsorption capacity reached 94.8 mg/g, which is twice
      that of nonmolecularly imprinted polymers, and satisfactory selectivity and
      reproducibility were achieved. Using the Lys-MIP column, lysozyme could be
      separated completely from egg white, with purity close to 100% and mass recovery
      of 98.2%. This illustrated that the synthesized Lys-MIPs had high specific
      recognition and selectivity to the template lysozyme when they were applied to a
      mixture of protein standards and a real sample.

PMID- 24861764
TI  - Improved analysis of vitamin D metabolites in plasma using liquid chromatography
      tandem mass spectrometry, and its application to cardiovascular research.
AB  - The accurate and specific measurement of vitamin D is increasingly important for
      determining the role of vitamin D in the pathogenesis of disease. Liquid
      chromatography coupled to tandem mass spectrometry (LC/MS/MS) has increasingly
      become the analytical modality of choice for the analysis of vitamin D. There are
      many advantages to using LC/MS/MS, such as high specificity and sensitivity to
      help distinguish the isomers of vitamin D. This rapid method, modified from a
      Waters Corporation application note, consists of minimal sample manipulation
      using liquid-liquid extraction and incorporates an internal standard. The
      supernatant is dried down and injected onto an ultra-high-performance liquid
      chromatography/electrospray ionization tandem mass spectrometer. The total
      analysis time is 10 min per injection, enabling high throughput of samples. This
      method also incorporates two commercial quality control standards to provide a
      robust system with acceptable coefficient of variation. The analysis of control
      and heart failure plasma samples showed significant differences in the levels of
      vitamin D3 between these two groups; however, in the control group, there were
      individuals who were vitamin D deficient. Overall, the vitamin D3 levels were
      higher in control samples than in heart failure individuals. As expected, vitamin
      D2 levels were not observed in many of the samples analysed. This modified method
      is quick and incorporates an internal standard to allow for any loss in the
      extraction procedure. The method also includes quality control samples to enable
      assay standardization. The assay involves inexpensive pre-sample clean-up, aiding
      high throughput, which is important in many laboratories.

PMID- 24861766
TI  - Regulation of ubiquitin-specific processing protease 8 suppresses
      neuroinflammation.
AB  - In our previous study, we reported that luteolin might exert neuroprotective
      functions by inhibiting the production of proinflammatory mediators, thereby
      suppressing microglial activation. In this study, we used two-dimensional gel
      electrophoresis (2-DE) and mass spectrometry (MS) to study the effect of
      ubiquitin-specific processing protease 8 (USP8) in luteolin-treated microglia.
      Western blot analysis verified that USP8 expression is upregulated by luteolin.
      Researchers have found that USP8 markedly enhanced the stability of neuregulin
      receptor degradation protein-1 (Nrdp1), which in turn inhibited the production of
      proinflammatory cytokines in toll-like receptor-triggered macrophages. We next
      hypothesized that luteolin inhibits microglial inflammation by regulating USP8
      gene expression. After transfecting BV2-immortalized murine microglial cells with
      USP8, a significant reduction in the degradation of Nrdp1 was observed. USP8
      overexpression also reduced the production of lipopolysaccharide (LPS)-induced
      proinflammatory mediators such as inducible nitric oxide synthase (iNOS), nitric
      oxide (NO), cyclooxygenase-2 (COX-2), and prostaglandin E2 (PGE2). We also found
      that USP8 siRNA blocked luteolin inhibition of pro-inflammatory gene expression
      such as iNOS, NO, COX-2, and PGE2. Taken together, our findings suggested that
      luteolin inhibits microglial inflammation by enhancing USP8 protein production.
      We concluded that in addition to anti-inflammatory luteolin, USP8 might represent
      a novel mechanism for the treatment of neuroinflammation and neurodegeneration. 

PMID- 24861768
TI  - Are two intrauterine contraceptive devices better than one?

PMID- 24861767
TI  - New epidemiology of Staphylococcus aureus infection in Africa.
AB  - Research on African Staphylococcus aureus has been largely neglected in the past,
      despite the cultural and geographical diversity in Africa, which has a
      significant impact on the epidemiology of this pathogen. The polarity between
      developed urban societies and remote rural populations (e.g. Pygmies), combined
      with close contact with animals (e.g. livestock and domestic animals, and
      wildlife), makes the epidemiology of S. aureus on the African continent unique
      and fascinating. Here, we try to draw an epidemiological picture of S. aureus
      colonization and infection in Africa, and focus on the wide spread of Panton
      Valentine leukocidin-positive isolates, the emergence of the hypervirulent
      methicillin-resistant S. aureus (MRSA) clone USA300, and the dissemination of the
      typical African clone MRSA sequence type 88.

PMID- 24861770
TI  - How do nurses in palliative care perceive the concept of self-image?
AB  - BACKGROUND: Nursing research indicates that serious illness and impending death
      influence the individual's self-image. Few studies define what self-image means.
      Thus it seems to be urgent to explore how nurses in palliative care perceive the
      concept of self-image, to get a deeper insight into the concept's applicability
      in palliative care. AIM: To explore how nurses in palliative care perceive the
      concept of self-image. DESIGN: Qualitative descriptive design. METHOD: In-depth
      interviews with 17 nurses in palliative care were analysed using phenomenography.
      The study gained ethical approval. RESULTS: The concept of self-image was
      perceived as both a familiar and an unfamiliar concept. Four categories of
      description with a gradually increasing complexity were distinguished: Identity,
      Self-assessment, Social function and Self-knowledge. They represent the
      collective understanding of the concept and are illustrated in a 'self-image
      map'. The identity-category emerged as the most comprehensive one and includes
      the understanding of 'Who I am' in a multidimensional way. CONCLUSION: The
      collective understanding of the concept of self-image include multi-dimensional
      aspects which not always were evident for the individual nurse. Thus, the concept
      of self-image needs to be more verbalised and reflected on if nurses are to be
      comfortable with it and adopt it in their caring context. The 'self-image map'
      can be used in this reflection to expand the understanding of the concept. If the
      multi-dimensional aspects of the concept self-image could be explored there are
      improved possibilities to make identity-promoting strategies visible and support
      person-centred care.

PMID- 24861769
TI  - Therapeutic monitoring of pediatric renal transplant patients with conversion to
      generic cyclosporin.
AB  - BACKGROUND: Cyclosporin is a calcineurin inhibitor widely used in renal
      transplant patients to prevent organ rejection. Several position papers have been
      published but no reports on the practical experience in pediatric patients
      undergoing conversion between cyclosporin innovator and generic products are
      available. OBJECTIVE: To evaluate the pharmacokinetics and safety as part of
      therapeutic monitoring of cyclosporin in renal transplant pediatric patients who
      switch from the innovator to the generic formulation in Argentina. SETTING:
      Hospital de Pediatria JP Garrahan, Buenos Aires, Argentina. METHODS: Stable
      pediatric renal transplant patients (6 months post-transplant) switched from the
      innovator to the generic formulation of cyclosporin microemulsion capsule.
      Cyclosporin pharmacokinetic parameters were obtained while taking the innovator
      and after starting with the generic formulation. Blood samples were drawn before
      and 1, 2, and 3 h after drug administration and subsequently quantified.
      Pharmacokinetic parameters were obtained by means of a Bayesian approach. MAIN
      OUTCOMES MEASURE: Cyclosporin pharmacokinetic parameters (area under the curve,
      AUC; Blood concentration after 2 h, C2), adverse events and graft rejection.
      RESULTS: A total of 12 patients were included. Median (range) age and time post
      transplant were 10.7 years (6.5-17.7) and 8.3 years (3.4-14.0), respectively. Two
      patients or their parents did not consent to the switch. Median (range) dose
      normalized cyclosporin AUC and C2 were 1.15 (mg*h/L)/mg/kg (0.72-3.0) and 265.5
      (ng/ml)/mg/kg (120.8-725.7), respectively, on the innovator therapy and 1.05
      (mg*h/L)/mg/kg (0.54-2.22) and 317.1 (ng/ml)/mg/kg (116.7-564.7) for the generic
      drug after the switch. The median (range) percentage of change in the AUC and C2
      when switching between formulations were 16.7 % (0.7-56.7) and 13.1 % (3.7-68.6),
      respectively. No significant changes in serum creatinine levels were registered
      when comparing before and after substitution of products. Adverse events (number
      of events) recorded 5 months before and after the switch included hirsutism (2),
      hypertension (2), and gingival hyperplasia (1). CONCLUSION: Conversion of
      cyclosporin from innovator brand to generic in pediatric renal transplant
      patients needs to be closely monitored.

PMID- 24861771
TI  - Higher systolic blood pressure with normal vascular function measurements in
      preterm-born children.
AB  - Preterm birth, low birth weight and poor foetal nutrition have been linked to
      cardiovascular disease, but the underlying mechanisms remain unclear. We explored
      prematurity and vascular function by studying a UK cohort of 14 049 children and
      conducting a systematic review. CONCLUSION: Systolic blood pressure was higher in
      subjects born preterm than term, but there were no differences in endothelial
      dysfunction or arterial stiffness. The systematic review revealed no clear
      association between prematurity and vascular function.

PMID- 24861774
TI  - Organic fluorescent thermometers based on borylated arylisoquinoline dyes.
AB  - Borylated arylisoquinolines with redshifted internal charge-transfer (ICT)
      emission were prepared and characterized. Upon heating, significant fluorescence
      quenching was observed, which forms the basis for a molecular thermometer. In the
      investigated temperature range (283-323 K) an average sensitivity of -1.2 to 
      1.8% K(-1) was found for the variations in fluorescence quantum yield and
      lifetime. In the physiological temperature window (298-318 K) the average
      sensitivity even reaches values of up to -2.4% K(-1). The thermometer function is
      interpreted as the interplay between excited ICT states of different geometry. In
      addition, the formation of an intramolecular Lewis pair can be followed by (11)B
      NMR spectroscopy. This provides a handle to monitor temperature-dependent ground
      state geometry changes of the dyes. The role of steric hindrance is addressed by
      the inclusion of a derivative that lacks the Lewis pair formation.

PMID- 24861772
TI  - Association of interleukin-23 receptor gene polymorphisms with risk of bladder
      cancer in Chinese.
AB  - To assess whether polymorphisms of the interleukin-23 receptor (IL23R) gene are
      associated with bladder transitional cell carcinoma because chronic inflammation
      contributes to bladder cancer and the IL23R is known to be critically involved in
      the carcinogenesis of various malignant tumors. 226 patients with bladder cancer
      and 270 age-matched controls were involved in the study. Polymerase chain
      reaction-restriction fragment length polymorphism was used for genotyping.
      Genotype distribution and allelic frequencies between patients and controls were
      compared. In all three single nucleotide polymorphisms of IL23R studied, the
      distribution of genotype and allele frequencies of rs10889677 differed
      significantly between patients and controls. The frequency of allele C of
      rs10889677 was significantly increased in cases compared with controls (0.2898
      vs. 0.1833, odds ratio 1.818, 95 % confidence interval 1.349-2.449). The result
      indicates that IL23R may play an important role in the susceptibility of bladder
      cancer in Chinese population.

PMID- 24861773
TI  - Effects of colistin on the sensory nerve conduction velocity and F-wave in mice.
AB  - The aim of this study was to examine the changes of sensory nerve conduction
      velocity (SNCV) and F-wave for colistin-induced peripheral neurotoxicity using a
      mouse model. Mice were administered with colistin 5, 7.5 and 15 mg/kg/day via a 3
      min. intravenous infusion. The sensory nerve conduction velocity (SNCV) and F
      wave were measured using the bipolar recording electrodes. The SNCV and F-wave
      latency changed in a dose- and time-dependent manner. The significant increase of
      F-wave latency and significant decrease of SNCV appeared on day 3 (p < 0.05 and
      0.01, respectively) in the 15 mg/kg/day group, and they were markedly changed on
      day 7 in the 7.5 mg/kg/day (p < 0.01 and 0.05, respectively) and 15 mg/kg/day
      groups (both p < 0.01). In addition, F-wave latency also significantly increased
      on day 7 in the 5 mg/kg/day group (p < 0.05) without any clinical signs. These
      results indicate that SNCV and F-wave latency were more sensitive in colistin
      induced neurotoxicity in mice, which highlights the early monitoring tool of
      polymyxins neurotoxicity in the clinic. 

PMID- 24861775
TI  - Targeting angiotensin-converting enzyme 2 as a new therapeutic target for
      cardiovascular diseases.
AB  - Angiotensin-converting enzyme 2 (ACE2) is a monocarboxypeptidase that metabolizes
      several vasoactive peptides, including angiotensin II (Ang-II; a
      vasoconstrictive/proliferative peptide), which it converts to Ang-(1-7). Ang-(1
      7) acts through the Mas receptor to mediate vasodilatory/antiproliferative
      actions. The renin-angiotensin system involving the ACE-Ang-II-Ang-II type-1
      receptor (AT1R) axis is antagonized by the ACE2-Ang-(1-7)-Mas receptor axis. Loss
      of ACE2 enhances adverse remodeling and susceptibility to pressure and volume
      overload. Human recombinant ACE2 may act to suppress myocardial hypertrophy,
      fibrosis, inflammation, and diastolic dysfunction in heart failure patients. The
      ACE2-Ang-(1-7)-Mas axis may present a new therapeutic target for the treatment of
      heart failure patients. This review is mainly focused on the analysis of ACE2,
      including its influence and potentially positive effects, as well as the
      potential use of human recombinant ACE2 as a novel therapy for the treatment
      cardiovascular diseases, such as hypertension and heart failure.

PMID- 24861777
TI  - Surfactant concentration dependent spectral effects of oxygen and depletion
      interactions in sodium dodecyl sulfate dispersions of carbon nanotubes.
AB  - Quenching of optical absorbance spectra for carbon nanotubes (CNTs) dispersed in
      sodium dodecyl sulfate (SDS) has been observed to be more pronounced at higher
      concentrations of the surfactant. The protonation-based quenching behavior
      displays wavelength dependence, affecting larger diameter nanotube species
      preferentially. Although absorbance may be recovered by hydroxide addition, pH
      measurements suggest that hydrolysis of SDS does not play a major role in the
      short term quenching behavior at high SDS concentrations. The degree of quenching
      is observed to correlate well with an increase in attractive depletion as SDS
      concentration is increased, while the extent of depletion is found to depend
      heavily on the concentration of preparation in comparison to the final SDS
      concentration. Attractive depletion in SDS is also found to be preferential for
      CNTs of larger diameter. It is proposed that depletion enhances the quenching
      effect due to close association of CNT-SDS complexes providing higher SDS
      densities on the CNT surface, leading to further oxidation. In addition, the
      quenching behavior in SDS is found to strongly suppress the optical and Raman
      signal from metallic nanotube species even at high pH. Displacement of SDS by
      sodium deoxycholate as a secondary surfactant is able to reverse the effects of
      protonation of metallic species, whereas hydroxide addition is only partially
      effective. 

PMID- 24861776
TI  - Managing postmenopausal women with hormone receptor-positive advanced breast
      cancer who progress on endocrine therapies with inhibitors of the PI3K pathway.
AB  - Although endocrine therapies that interfere with estrogen receptor (ER)-mediated
      signaling have revolutionized the management of postmenopausal women with hormone
      receptor-positive (HR+) breast cancer (BC), long-term management of these
      patients is suboptimal because of the eventual emergence of endocrine resistance.
      Intense research has elucidated a number of targets that act downstream or
      upstream of the ER, as well as those that crosstalk with the ER; however,
      clinical validation of inhibiting specific targets to overcome endocrine
      resistance has been lacking. The phosphatidylinositol 3-kinase (PI3K)/protein
      kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway has been implicated
      to mediate endocrine resistance, and a number of novel agents that target this
      pathway are in early- and late-stage clinical trials. Recently, everolimus, an
      inhibitor of mTOR, a critical component of the PI3K/AKT/mTOR pathway, in
      combination with endocrine therapy, was shown to prolong progression-free
      survival with a manageable adverse-event profile in postmenopausal patients with
      HR+ BC. Bolstered by the safety and efficacy observed with concomitant inhibition
      of the ER and the PI3K/mTOR pathway and the validation of dual inhibition
      approach in managing postmenopausal patients with HR+ BC, a number of novel
      agents that inhibit PI3K (pan-PI3K inhibitors) or PI3K and mTOR (dual PI3K/mTOR)
      are being evaluated in clinical trials. Thus, mTOR inhibitors have provided the
      much-needed ammunition to oncologists who manage postmenopausal women with BC and
      have paved the way for the development of novel therapies that target the
      PI3K/mTOR pathway. Use of these novel therapies in managing postmenopausal women
      with BC, in combination with endocrine therapies, is expected to improve overall
      outcomes by overcoming endocrine resistance. 

PMID- 24861778
TI  - Rhinosinusitis in oral medicine and dentistry.
AB  - Rhinosinusitis is a very common condition which is normally readily recognizable.
      Given the intimate anatomic relationship between the antrum and the posterior
      maxillary teeth, maxillary sinusitis can present as odontalgia. Distinguishing
      between odontogenic orofacial pain and pain associated with maxillary sinusitis
      is important to prevent unnecessary dental intervention and to direct patients to
      medical colleagues. Conversely, odontogenic infection can spread to involve the
      antrum, termed odontogenic sinusitis, or maxillary sinusitis of dental origin.
      Odontogenic sinusitis accounts for about 10-40% of all cases of sinusitis, and
      usually requires combined dental and medical treatment. Maxillary sinusitis can
      also be a complication of exodontia, resulting from tuberosity fractures,
      displaced teeth or root fragments and the creation of oroantral communications
      and fistulae. Dental implants and endodontic materials can also impinge on the
      maxillary sinus, and are rare causes of sinusitis. Often it is stated that
      rhinosinusitis may contribute to a halitosis complaint, and widely used
      diagnostic protocols for rhinosinusitis sometimes list halitosis as a minor
      criterion. However, gold standards in halitotosis research such as organoleptic
      assessment or gas chromatography have not been used to validate a correlation
      between objective (genuine) halitosis and sinusitis. The pathophysiology of this
      mechanism is unclear, and the relative importance of this alongside other causes
      of extraoral halitosis is debated. 

PMID- 24861781
TI  - Constant pressure mode extended simple gradient liquid chromatography system for
      micro and nanocolumns.
AB  - Performing gradient liquid chromatography at constant pressure instead of
      constant flow rate has serious potential for shortening the analysis time and
      increasing the productivity of HPLC instruments that use gradient methods.
      However, in the constant pressure mode the decreasing column permeability during
      a long period of time negatively affects the repeatability of retention time.
      Thus a volume-based approach, in which the detector signal is plotted as a
      function of retention volume, must be taken into consideration. Traditional HPLC
      equipment, however, requires quite complex hardware and software modifications in
      order to work at constant pressure and in the volume-based mode. In this short
      communication, a low cost and easily feasible pressure-controlled extension of
      the previously described simple gradient liquid chromatography platform is
      proposed. A test mixture of four nitro esters was separated by 10-60% (v/v)
      acetone/water gradient and a high repeatability of retention volumes at 20MPa
      (RSD less than 0.45%) was realized. Separations were also performed at different
      values of pressure (20, 25, and 31MPa), and only small variations of the
      retention volumes (up to 0.8%) were observed. In this particular case, the gain
      in the analysis speed of 7% compared to the constant flow mode was realized at a
      constant pressure. 

PMID- 24861780
TI  - Hidden in plain sight: spike-wave discharges in mouse inbred strains.
AB  - Twenty-seven inbred strains of mice were tested for spike-wave discharge (SWD)
      activity by video-electroencephalographic recordings over a 24-h recording
      period. Eight strains had reproducible, frequent SWDs, including five strains
      (C57BLKS/J, CBA/J, DBA/1J, NOR/LtJ, SM/J) previously undiagnosed for this
      distinctive phenotype. Eighteen other strains exhibited no such activity. Spike
      wave discharges usually occurred while the subject was motionless, and in a
      significant number of annotated instances coincided with an arrest of the
      subject's relatively unrestrained locomotor activity, which resumed immediately
      after the discharge ended. In all five new strains, SWDs were suppressed by
      ethosuximide administration. From the genealogy of inbred strains, we suggest
      that two ancestors, A and DBA, transmitted genotypes required for SWD in all
      positive strains. Together these strains with SWDs provide new opportunities to
      understand the genetic core susceptibility of this distinctive
      electroencephalographic activity and to explore its relationship to absence
      epilepsy, a human disorder for which few genes are known. 

PMID- 24861782
TI  - Computerized optimization of flows and temperature gradient in flow modulated
      comprehensive two-dimensional gas chromatography.
AB  - Informational entropy and syentropy percent were used to optimize the flows in
      the first (1D) and in the second (2D) dimension ((1)Fm and (2)Fm, respectively)
      as well as the temperature program rate (r) for the flow modulated GC*GC-FID
      separation of C6-C12 aromatic hydrocarbons in a low boiling petrochemical sample.
      The separations were performed on a column series consisting of a 25m*0.25mm
      i.d.*0.2MUm df of the polar ionic liquid SLB-IL 100 (1,9-di(3
      vinylimidazolium)nonane bis(trifluoromethylsulfonyl)imide) in the first dimension
      and 5m*0.25mm i.d.*0.25MUm df apolar HP-5MS (5% phenyl-95% methylpolysiloxane) in
      the second dimension. A dependence of a distribution of individual aromatic
      hydrocarbons in the 2D retention plane on the carrier gas flows ((1)Fm, and
      (2)Fm,) and temperature gradient (r) was examined in this study. It was found
      that informational entropy and synentropy percent are advantageous criteria to
      characterize the distribution of peaks in the 2D retention plane. Maximum
      informational entropy and synentropy percents correspond to the maximum
      distribution of C6-C12 aromatic hydrocarbons in the corresponding 2D retention
      plane gained by the given separation using optimized values of individual carrier
      gas column volume flows and the temperature rate at the temperature programmed
      GC*GC separations. 

PMID- 24861783
TI  - Study of deoxyribonucleic acid-ligand interactions by partial filling affinity
      capillary electrophoresis.
AB  - In this work, a new partial filling affinity capillary electrophoresis (PF-ACE)
      method has been developed and applied to investigation of non-covalent molecular
      interactions between double stranded DNA oligonucleotide (Dickerson dodecamer)
      and classical DNA intercalator ligand-ethidiumbromide (EtBr) or oligophenylene
      derivatives-based potential new type of DNA ligands. Binding constants of DNA
      ligand complexes were determined from the dependence of migration time changes of
      DNA oligomer (applied as analyte) on the length of ligand zones introduced
      beforehand as plugs of various lengths (0-75mm with 12.5mm step) in
      hydroxypropylcellulose coated fused silica capillary of 50/375MUm I.D./O.D. and
      400/300mm total/effective length. PF-ACE experiments were performed in two
      background electrolytes, Tris-borate, pH 8.0, ionic strength 14.3mM (BGE1), and
      sodium phosphate, pH 7.5, ionic strength 133mM (BGE2). Binding constants of DNA
      EtBr complex (ca 15300L/mol in the BGE1 and 4200L/mol in the BGE2) were found to
      be significantly higher than those of DNA complexes with oligophenylene
      derivatives (ca 2200-3600L/mol in the BGE1 and 1600-2300L/mol in the BGE2). 

PMID- 24861784
TI  - Rapid determination of methanol content in paper materials by alkaline
      extraction, coupled with headspace analysis.
AB  - This study reports on a rapid method for the determination of methanol in paper
      based materials by alkaline extraction, coupled with headspace analysis. Methanol
      partition equilibria between solid-liquid phases and vapor-liquid phases were
      conducted in two separate containers, from which an equation for calculating the
      total methanol content in the original paper sample was derived. It was found
      that the extraction equilibrium of methanol from solid sample could be achieved
      within 5min at room temperature using a high-speed disintegrator, and a
      subsequent neutralization step is an effective way to prevent methanol from being
      regenerated at high temperature during headspace equilibration. The results
      showed that the relative standard deviations for reproducibility tests were in
      the range of 1.86-6.03%, and the recoveries were in the range of 92.3-107%. The
      present method is simple and practical; it can be an efficient tool for
      quantifying the methanol content in paper-based materials and thus play an
      important role in the investigation of methanol migration behavior in food and
      beverage packaging. 

PMID- 24861785
TI  - Octaproline, a conformationally flexible chiral selector in liquid
      chromatographic enantioseparation.
AB  - A proline octapeptide-derived chiral selector (CS) end-capped using a pivaloyl
      group was covalently linked to a silica gel chromatographic matrix by the C
      terminal group. The chromatographic behaviour of the resulting chiral stationary
      phase (CSP) using different conditions was compared to those containing 3,5
      dimethylphenylcarbamate residues on the proline units. An enantioseparation
      ability highly dependent on the mobile phase used is observed for these CSPs.
      When mixtures of alkane/alcohol or alkane/ether are used as mobile phase a
      similar enantioselectivity is obtained. Nevertheless, in the presence of
      chlorinated solvents, and without a hydrogen bonding donor in the mobile phase,
      enantioselectivity is extremely reduced. The reversibility of this phenomenon,
      attributed to a conformational change in the CS, is examined. 

PMID- 24861786
TI  - Targeted profiling of polar intracellular metabolites using ion-pair-high
      performance liquid chromatography and -ultra high performance liquid
      chromatography coupled to tandem mass spectrometry: applications to serum, urine
      and tissue extracts.
AB  - The effective analysis of polar ionic metabolites by LC-MS, such as those
      encountered in central carbon metabolism, represents a major problem for
      metabolic profiling that is not adequately addressed using strategies based on
      either reversed-phase or HILIC methods. Here we have compared analysis of central
      carbon metabolites on optimized methods using HILIC, porous graphitic carbon or
      ion pair chromatography (IPC) using tributyl ammonium as IP reagent. Of the 3
      chromatographic approaches examined only IPC enabled us to obtain a robust
      analytical methodology. This system was used to profile more than a hundred
      endogenous metabolic intermediates in urine, serum and tissue samples. However,
      whilst we found IPC to be the best of the approaches examined considerable care
      was still needed to obtain robust data. Thus, in excess of 40 of representative
      biological samples were needed to "condition" a new analytical column and further
      10 matrix injections were then required at the beginning of each analytical batch
      in order to obtain robust and reproducible chromatographic separations. An
      additional limitation that we have found was that, for a small number of
      phosphorylated and poly carboxylic acid metabolites, measurement was only
      possible if the analytes were present in relatively high concentrations. We also
      found that, whilst this methodology could be used for the analysis of both in
      vitro cell culture media, cell extracts, tissue, and biological fluids (blood,
      urine), for the best results columns should only be used to analyze a single
      matrix. However, despite the need for extensive column conditioning, and the
      manifold disadvantages resulting from the contamination of the separation system
      and mass spectrometer with the ion pair reagent, IPC-MS currently provides the
      best means of analyzing these polar, ionic and problematic metabolites. 

PMID- 24861787
TI  - A new stationary phase for high performance liquid chromatography: Calix[4]arene
      derivatized chitosan bonded silica gel.
AB  - In the present paper, a new calix[4]arene derivatized chitosan bonded stationary
      phase (CCS4) for high performance liquid chromatography (HPLC) was synthesized
      and characterized. Its chromatographic performance and retention mechanism were
      evaluated in reversed-phase mode compared with ODS using different solute probes
      including mono-substituted benzenes, phenols and nucleosides. The results showed
      that CCS4 stationary phase could provide various interactions with solutes, such
      as hydrophobic, hydrophilic, pi-pi, and inclusion interactions. It could perform
      the mixed-mode separation including RP and HILIC. 

PMID- 24861788
TI  - Fast carbohydrate analysis via liquid chromatography coupled with ultra violet
      and electrospray ionization ion trap detection in 96-well format.
AB  - A fast carbohydrate screening platform processible in 96-well format is
      described. The method is suitable for the determination of various carbohydrates
      out of complex mixtures as obtained by acidic hydrolysis of carbohydrates
      polymers. The chromatographic conditions for an efficient separation (12min) and
      the derivatization process with 1-phenyl-3-methyl-5-pyrazolone (PMP) were
      optimized for high resolution separation and simultaneous determination of deoxy
      , amino-, anhydro-sugars as well as hexoses, pentoses, dimers, uronic acids and
      degradation products like furfural and hydroxymethylfurfural (HMF). The potential
      to quantify with UV- and MS-detector in the same range has been demonstrated for
      20 different compounds. Finally, the matrix effects of the hydrolysis were
      positively evaluated. The micro scale hydrolysis and PMP-derivatization without
      any extraction or drying steps, both in 96-well format, result in a fast and
      intuitive sample preparation. In combination with a fast liquid chromatography
      coupled to UV and electrospray ionization ion trap detection (LC-UV-ESI-MS/MS)
      for the qualification and quantification of various sugars, dimers and
      degradation products, this method shows great performance in carbohydrate
      analysis. 

PMID- 24861789
TI  - Application of electro-enhanced solid phase microextraction combined with gas
      chromatography-mass spectrometry for the determination of tricyclic
      antidepressants in environmental water samples.
AB  - A fast and efficient method for the determination of tricyclic antidepressants
      using electro-enhanced solid phase microextraction (SPME) coupled to gas
      chromatography-mass spectrometry (GC-MS) has been developed. One advantage of
      this approach is that the mass transfer of target analytes from the sample
      solution to an SPME fiber can be accelerated by the electrical field, improving
      extraction selectivity and efficiency. In the present work, the target analytes
      extracted to the SPME fiber were thermally desorbed in the GC injection port
      after extraction. Under the optimized extraction conditions, the developed method
      exhibited low limits of detection (between 0.079 and 0.296MUg/L) and good
      linearity over the concentration range of between 1 and 500MUg/L with
      coefficients of determination (r(2)) of between 0.993 and 0.999. The relative
      standard deviations were lower than 9.2% for all analytes. The proposed method
      was applied to extract tricyclic antidepressants in environmental water samples. 

PMID- 24861790
TI  - Gas chromatography and ultra high performance liquid chromatography tandem mass
      spectrometry methods for the determination of selected endocrine disrupting
      chemicals in human breast milk after stir-bar sorptive extraction.
AB  - In the present work, two specific, accurate and sensitive methods for the
      determination of endocrine disrupting chemicals (EDCs) in human breast milk are
      developed and validated. Bisphenol A and its main chlorinated derivatives, five
      benzophenone-UV filters and four parabens were selected as target analytes. The
      method involves a stir-bar sorptive extraction (SBSE) procedure followed by a
      solvent desorption prior to GC-MS/MS or UHPLC-MS/MS analysis. A derivatization
      step is also necessary when GC analysis is performed. The GC column used was a
      capillary HP-5MS with a run time of 26min. For UHPLC analysis, the stationary
      phase was a non-polar Acquity UPLC((r)) BEH C18 column and the run time was
      10min. In both cases, the analytes were detected and quantified using a triple
      quadrupole mass spectrometer (QqQ). Quality parameters such as linearity,
      accuracy (trueness and precision), sensitivity and selectivity were examined and
      yielded good results. The limits of quantification (LOQs) ranged from 0.3 to
      5.0ngmL(-1) for GC and from 0.2 to 1.0ngmL(-1) for LC. The relative standard
      deviation (RSD) was lower than 15% and the recoveries ranged from 92 to 114% in
      all cases, being slightly unfavorable the results obtained with LC. The methods
      were satisfactorily applied for the determination of target compounds in human
      milk samples from 10 randomly selected women. 

PMID- 24861791
TI  - Direct oral anticoagulants (DOACs) versus "new" oral anticoagulants (NOACs)?

PMID- 24861792
TI  - Direct oral anticoagulants--pharmacology, drug interactions, and side effects.
AB  - The direct thrombin inhibitor, dabigatran, as well as the direct factor Xa
      inhibtors rivaroxaban, apixaban, and edoxaban, display pharmacodynamic features
      quite similar to low-molecular-weight heparins, with a time to peak level of 1-4
      hours after oral administration, and a half-life between 5 and 14 hours. All
      drugs display a linear relationship and a high degree of correlation between drug
      levels in plasma, and the anticoagulant effect. Major differences are the extent
      of renal elimination (with 80% or more for dabigatran, 66% for rivaroxaban [33%
      unchanged, active drug, and 33% inactive metabolites], 33% for edoxaban, and
      finally, 25% for apixaban), and bioavailability, which determines the amount of
      drug required for attaining the target plasma concentration of the drug. Due to
      the reliable pharmacokinetics and pharmacodynamics, no routine laboratory
      monitoring is necessary, although dedicated laboratory assays are available for
      emergencies and some other specific conditions. 

PMID- 24861793
TI  - Direct oral anticoagulants--interference with laboratory tests and mechanism of
      action.
AB  - Direct oral anticoagulants (DOACs) have been established and already registered
      for clinical use on a wide basis in the United States and Europe. Different from
      the vitamin K antagonists (VKA), their mode of action is based on the direct
      inhibition of the single coagulation enzymes factor Xa or IIa. Other laboratory
      tests of hemostasis, such as the global tests prothrombin time (PT/INR) and
      activated partial thromboplastin time (APTT), or various functional coagulation
      assays involving generation of factor Xa or IIa for their endpoints, can be
      negatively influenced by the presence of the anticoagulant in the test sample.
      This interference has been well documented for rivaroxaban, apixaban, and
      dabigatran and is most prominent during the first hours after intake of the
      respective agent. Thus, the potential influence of DOACs has always to be
      considered when interpreting abnormal functional coagulation assays. 

PMID- 24861794
TI  - Direct oral anticoagulants and bleeding risk (in comparison to vitamin K
      antagonists and heparins), and the treatment of bleeding.
AB  - Direct oral anticoagulants (DOACs), direct inhibitors of thrombin or factor Xa
      (FXa), are increasingly used in clinical practice for the prevention of
      thromboembolic complications in patients with non-valvular atrial fibrillation
      (NVAF) and for therapy of venous thromboembolism (VTE). Like any anticoagulant
      treatment, their use is associated with the risk of bleeding events. The first
      aim of this article is to review the data on bleeding complications from the
      phase III clinical studies on chronic use of DOACs and from the few available
      phase IV registers in use of these drugs. In all randomized studies the DOACs
      showed a statistical non-inferiority for safety versus comparators (in most cases
      warfarin), although the rates of major bleeding were significantly lower for some
      DOACs and treatment doses than for warfarin. Data from available phase IV
      registers confirm that the use of DOACs in clinical practice is not associated
      with higher bleeding rates versus warfarin. Secondly, we will try to propose a
      possible treatment of bleeding complications associated with DOACs. Given the
      absence of specific antidotes, strategies for proper treatment of bleeding events
      are crucial; however, due to the lack of data, only proposals rather than
      recommendations are possible. 

PMID- 24861795
TI  - Perioperative management issues of direct oral anticoagulants.
AB  - The treatment repertoire of oral anticoagulation has changed dramatically over
      the past few years from one class of vitamin K1 antagonists to an increasing
      number of direct oral anticoagulants (DOACs). Clinicians are confronted with the
      problem of managing patients on novel agents in the critical setting before,
      during, and after surgery, where the risk of bleeding and thrombosis are
      increased simultaneously. Randomized clinical data are insufficient to date, but
      clinical exposure enlarges the body of experience. The following review considers
      perioperative management issues in various categories, including minor elective
      surgery, major elective surgery, and acute surgery. This review is a credo to
      personalized medicine where the patient's underlying thromboembolic risk status,
      the potential bleeding risk, or actual hemorrhagic manifestation determine the
      selection of multi-modal targeted management strategies. 

PMID- 24861796
TI  - Direct oral anticoagulants in the prevention of venous thromboembolism: evidence
      from major clinical trials.
AB  - Hospitalized medical and surgical patients encompass a group of patients in whom
      venous thromboembolism (VTE) poses a major concern on morbidity and mortality.
      Recently, direct oral anticoagulants for the prevention of VTE have been
      developed to overcome the drawbacks of the food/drug interactions and the need
      for frequent laboratory monitoring and dose adjustments associated with the use
      of vitamin K antagonists and the inconvenience of the subcutaneous administration
      of low-molecular-weight heparins and fondaparinux. The novel oral anticoagulants
      that have been tested in major clinical trials for VTE prevention in medical and
      surgical patients are the thrombin inhibitor dabigatran and the factor Xa
      inhibitors apixaban, rivaroxaban, and edoxaban, which will be the focus of this
      review. While the new drugs proved to be highly effective and safe in the
      prevention of VTE following major orthopedic surgery, they failed to show a
      favorable benefit-to-risk profile in hospitalized medical patients receiving
      extended anticoagulation beyond the hospital stay. 

PMID- 24861797
TI  - Direct oral anticoagulants in the management of venous thromboembolism--evidence
      from major clinical trials.
AB  - For decades the antithrombotic management of venous thromboembolism (VTE) was
      limited to parenteral heparin formulations and oral vitamin K antagonists. Even
      though both classes of anticoagulants are effective, they have several
      limitations, including a narrow therapeutic window and the need to monitor
      anticoagulant activity. Direct oral anticoagulants (DOACs) that specifically
      target factor IIa or Xa have emerged. Recent data suggest that they are at least
      as effective and as safe as conventional therapy and have practical advantages,
      such as fixed dose regimen and no need for laboratory monitoring. Hence, they
      represent a major step forward in the acute treatment and long-term prevention of
      VTE. In this review, we outline the use of DOACs in the management of VTE and
      provide an overview of recently published major trials. 

PMID- 24861798
TI  - Direct oral anticoagulants in atrial fibrillation.
AB  - Atrial fibrillation (AF), the most frequent sustained arrhythmia, is associated
      with an increased risk of thromboembolic events. The risk of stroke depends on
      risk factors such as age, hypertension, heart failure, and vascular disease.
      Thus, antithrombotic therapy is a cornerstone in the management of AF. Warfarin
      is successfully used to reduce thromboembolic events. More recently, direct
      thrombin (dabigatran) and factor Xa (apixaban, edoxaban, rivaroxaban) inhibitors
      have been compared to warfarin in large randomized trials. All new substances
      have been shown to be non-inferior to warfarin concerning thromboembolic events.
      Severe bleeding, such as fatal and intracranial bleeding, was less frequent with
      direct oral anticoagulants. Results of the studies and subgroup analyses are
      discussed. Further trials using direct oral anticoagulants in special populations
      such as very old and patients with kidney disease are needed. 

PMID- 24861799
TI  - Direct oral anticoagulants in acute coronary syndrome.
AB  - Patients with acute coronary syndromes (ACS) require a specific antithrombotic
      therapy in the immediate and the post ACS phase. The current antithrombotic
      therapy in the acute phase of an ACS combines antiplatelet and anticoagulant
      drugs in order to reduce ischemic cardiovascular events. In the post ACS phase,
      dual antiplatelet therapy (DAPT; aspirin and a P2Y12 receptor antagonist) is the
      current mainstay of antithrombotic treatment and is recommended in the guidelines
      of the major North American and European clinical cardiology associations (AHA,
      ACC, and ESC). Recently, the addition of rivaroxaban, a low dose oral direct
      factor Xa inhibitor (2.5 mg twice daily), to DAPT (aspirin plus second-generation
      P2Y12 inhibitor) showed a significant reduction of cardiovascular and overall
      mortality in the major phase III clinical trial ATLAS ACS 2 TIMI 51. This led to
      the approval of low-dose rivaroxaban in addition to aspirin and clopidogrel by
      the European Medicines Agency (EMA) in 2013. Other direct oral anticoagulants
      (apixaban, dabigatran etexilate) have also been assessed in phase II (dabigatran
      etexilate) and phase III (apixaban) post ACS clinical trials. In the studied
      dosing regimens, these drugs failed to show a net clinical benefit in addition to
      dual antiplatelet therapy. The major clinical phase II and III post ACS studies
      of direct oral anticoagulants are summarized and discussed in this article along
      with the concept of long-term anticoagulation for the secondary prevention of
      ischemic events after ACS and implications for the future of antithrombotic
      therapy in the current era of third-generation P2Y12 receptor inhibitors
      (Prasugrel and Ticagrelor). 

PMID- 24861800
TI  - The new direct oral anticoagulants in special indications: rationale and
      preliminary data in cancer, mechanical heart valves, anti-phospholipid syndrome,
      and heparin-induced thrombocytopenia and beyond.
AB  - The present review will briefly summarize the interplay between coagulation and
      inflammation, highlighting possible effects of direct inhibition of factor Xa and
      thrombin beyond anticoagulation. Additionally, the rationale for the use of the
      new direct oral anticoagulants (DOACs) for indications such as cancer-associated
      venous thromboembolism (CAT), mechanical heart valves, thrombotic anti
      phospholipid syndrome (APS), and heparin-induced thrombocytopenia (HIT) will be
      explored. Published data on patients with cancer or mechanical heart valves
      treated with DOAC will be discussed, as well as planned studies in APS and HIT.
      Although at the present time published evidence is insufficient for recommending
      DOAC in the above-mentioned indications, there are good arguments in favor of
      clinical trials investigating their efficacy in these contexts. Direct inhibition
      of factor Xa or thrombin may reveal interesting effects beyond anticoagulation as
      well. 

PMID- 24861801
TI  - New advances in protection against solar ultraviolet radiation in textiles for
      summer clothing.
AB  - Clothing is considered one of the most important tools for photoprotection
      against harmful solar ultraviolet radiation (UVR). The standard for sun
      protective clothing is based on erythema despite other biological effects of UVR
      on the skin. We analyzed the potential protection against UVR in fabrics destined
      for summer clothing based on several action spectra. We examined 50 garments
      classified by type of fabric composition, structure of the fiber yarn and color.
      The ultraviolet protection factor was calculated based on fabric ultraviolet
      transmittance corrected for erythema according to the EU standard E-13758 as well
      as the UVA transmittance of fabrics. UVR protection was also analyzed in base of
      different action spectra as for previtamin D3, nonmelanoma skin cancer,
      photoimmunosuppression and photoaging. Most knitted fabrics used for sports T
      shirts offered excellent ratings for ultraviolet protection while normal shirts
      showed very low ratings, particularly against photoaging. The cover is the most
      influential variable in fabric photoprotection, having an exponential
      relationship with the UPF. The relation between cover and UVA protection was
      linearly negative. Information about ultraviolet protection in textiles used for
      summer clothing should be included in labeling as some types of fabrics,
      especially those used for shirts, offer very low UVR protection. 

PMID- 24861802
TI  - Professional breastfeeding support for first-time mothers: a multicentre cluster
      randomised controlled trial.
AB  - OBJECTIVE: To evaluate the effect of two postnatal professional support
      interventions on the duration of any and exclusive breastfeeding. DESIGN:
      Multicentre, three-arm, cluster randomised controlled trial. POPULATION: A cohort
      of 722 primiparous breastfeeding mothers with uncomplicated, full-term
      pregnancies. METHODS: The three study interventions were: (1) standard postnatal
      maternity care; (2) standard care plus three in-hospital professional
      breastfeeding support sessions, of 30-45 minutes in duration; or (2) standard
      care plus weekly post-discharge breastfeeding telephone support, of 20-30 minutes
      in duration, for 4 weeks. The interventions were delivered by four trained
      research nurses, who were either highly experienced registered midwives or
      certified lactation consultants. MAIN OUTCOME MEASURES: Prevalence of any and
      exclusive breastfeeding at 1, 2, and 3 months postpartum. RESULTS: Rates of any
      and exclusive breastfeeding were higher among participants in the two
      intervention groups at all follow-up points, when compared with those who
      received standard care. Participants receiving telephone support were
      significantly more likely to continue any breastfeeding at 1 month (76.2 versus
      67.3%; odds ratio, OR 1.63, 95% confidence interval, 95% CI 1.10-2.41) and at 2
      months (58.6 versus 48.9%; OR 1.48, 95% CI 1.04-2.10), and to be exclusively
      breastfeeding at 1 month (28.4 versus 16.9%; OR 1.89, 95% CI 1.24-2.90).
      Participants in the in-hospital support group were also more likely to be
      breastfeeding at all time points, but the effect was not statistically
      significant. CONCLUSIONS: Professional breastfeeding telephone support provided
      early in the postnatal period, and continued for the first month postpartum,
      improves breastfeeding duration among first-time mothers. It is also possible
      that it was the continuing nature of the support that increased the effectiveness
      of the intervention, rather than the delivery of the support by telephone
      specifically.

PMID- 24861803
TI  - Differences in the reproductive hormone rhythm of tree sparrows (Passer montanus)
      from urban and rural sites in Beijing: the effect of anthropogenic light sources.
AB  - The pervasiveness of anthropogenic light in urban environments has increased the
      exposure to light of many animals. Since photoperiod is a regulator of the timing
      of reproduction in most temperate region birds, such light sources could
      potentially change the timing of reproduction. We compared the luteinizing
      hormone (LH), testosterone (T), and estradiol (E2) levels of tree sparrow (Passer
      montanus) populations sampled at two urban and two rural sites in China, and also
      performed a controlled photoperiod experiment to determine the influence of
      artificial light on the endocrine rhythm of these populations. LH levels of urban
      tree sparrows increased earlier than those of rural ones, but rural populations
      had higher LH peaks. A linear mixed model (LMM) indicates that increased exposure
      to light at night (LAN) significantly influenced the LH, T and E2 concentrations
      of free-living tree sparrows in urban environments compared to their rural
      counterparts. The results of the controlled photoperiod experiment showed that
      tree sparrows that were exposed to 6lux of light during the dark phase of the
      artificial photoperiod began to secrete LH earlier, and had lower peak LH levels,
      than control birds. A LMM indicates that LAN had a significant effect on LH
      levels in this experiment. Although urban tree sparrows began to secrete LH
      earlier than their rural counterparts, we found no corresponding advance in T or
      E2 secretion. On the contrary, peak T and E2 levels of urban birds were lower
      than those of rural birds. These results suggest that although anthropogenic
      light sources appear to advance the onset of LH secretion in urban tree sparrow
      populations, they also lower peak LH, and consequently levels of T and E2. A
      possible explanation for these observations is that greater exposure to
      anthropogenic light in urban environments stimulates LH secretion and may
      influence photosensitivity, but further experimental work is required to test
      this hypothesis. 

PMID- 24861804
TI  - Differential expression analysis of Paralichthys olivaceus microRNAs in adult
      ovary and testis by deep sequencing.
AB  - MicroRNAs (miRNAs) play an important role in gonadal development and
      differentiation in fish. However, understanding of the mechanism of this process
      is hindered by our poor knowledge of miRNA expression patterns in fish gonads. In
      this study, miRNA libraries derived from adult gonads of Paralichthys olivaceus
      were generated by using next-generation sequencing (NGS) technology.
      Bioinformatics analysis was performed to distinguish mature miRNA sequences from
      two classes of small RNAs represented in the sequencing data. A total of 141
      mature miRNAs were identified, in which 21 miRNAs were found in P. olivaceus for
      the first time. Variance and preference of miRNAs expression were concluded from
      the deep sequencing reads. Some miRNAs, such as pol-miR-143, pol-miR-26a and pol
      let-7a were found with quite high expression levels in both gonads, while some
      exhibited a clear sex-biased expression in different gonad. Approximate 20.0% and
      13.1% of the isolated miRNAs were preferentially expressed in the testis (FC<0.5)
      or ovary (FC>2), respectively. The identification and the preliminary analysis of
      the sex-biased expression of miRNAs in P. olivaceus gonads in our work by using
      NGS will provide us a basic catalog of miRNAs to facilitate future improvement
      and exploitation of sexual regulatory mechanisms in P. olivaceus. 

PMID- 24861805
TI  - Collaborative interaction of Oct-2 with Oct-1 in transactivation of lactogenic
      hormones-induced beta-casein gene expression in mammary epithelial cells.
AB  - Octamer-binding transcription factor-1 (Oct-1) is found to mediate lactogenic
      hormones (prolactin and glucocorticoids, HP)-induced beta-casein gene expression
      in mammary alveolar secretory epithelial cells (MECs). The mammary gland also
      expresses Oct-2 isoform. In this study, we show that Oct-2 is also involved in HP
      induced beta-casein expression. Oct-2 endogenously binds to the beta-casein
      promoter in MECs, and HP induce Oct-2 binding activity via mechanisms other than
      increasing Oct-2 expression or inducing Oct-2 translocation to the nucleus. Oct-2
      transactivates HP-induced beta-casein gene expression and this function is
      exchangeable with Oct-1. In MECs, Oct-2 is found to physically interact with Oct
      1 regardless of HP treatment. However, HP induce physical interactions of Oct-2
      with both signal transducer and activator of transcription 5 (STAT5) and
      glucocorticoid receptor (GR). These results provided biochemical evidence that
      Oct-2 may form a heteromer with Oct-1 in induction of beta-casein gene expression
      by HP in MECs. 

PMID- 24861806
TI  - Ticks on humans in the Pantanal wetlands, Brazil.
AB  - Information on ticks biting humans in Brazil is very restricted. In fact, many
      times when human tick-borne diseases are diagnosed, the involved vector tick is
      not identified, although this may be clinically helpful. Pantanal is one of the
      world's largest floodplains, has an exuberant wildlife, and is place of extensive
      cattle ranching, ecotourism, and fishing. We herein report tick species found on
      humans in a 13-month survey in a region with both cattle and wildlife handling in
      the Brazilian Pantanal. From February 2012 to February 2013, a total of 280 ticks
      was collected from humans (n=22), 121 of which were attached. Amblyomma
      cajennense sensu lato nymphs were the main tick species and stage found attached
      to humans (n=93) especially during the dry months (winter). In the wet season
      (summer), Amblyomma parvum adults were the main ticks found attached to humans
      (n=19) followed by A. cajennense s.l. adults (n=9). Only one unattached nymph of
      A. parvum was collected in this study. These results reinforce that A. cajennense
      s.l. nymphs are an important parasite of humans (and vectors) in Brazil and draw
      also attention to A. parvum adults as frequent human parasites as well. 

PMID- 24861808
TI  - Complexing ability of (-)-cytisine--synthesis, spectroscopy and crystal
      structures of the new copper and zinc complexes.
AB  - For the first time the NMR spectra of quinolizidine alkaloid with Cu(II) are
      studied. Structures of new complexes of (-)-cytisine with Cu(+2) and Zn(+2)
      cations are visualized, discussed in detail and characterized by spectroscopic
      methods: ESI-MS, NMR, UV-vis, EPR and crystallographic methods. In solution metal
      coordinates through the protonated nitrogen atoms of secondary amino groups (in
      piperidine ring) of cytisine molecule. While in solid state the most stable
      structures of the complexes are those in which the coordination of Cu(II) and
      Zn(II) salts is realized solely through the lactam carbonyl oxygen atom. 

PMID- 24861809
TI  - An integrated modeling approach to assessing linkages between environment,
      organism, and phenotypic plasticity.
AB  - Many of the most interesting questions in organismal biology, especially those
      involving the functional and adaptive significance of organismal characteristics,
      intrinsically transcend levels of biological organization. These organismal
      functions typically involve multiple interacting biological mechanisms. We
      suggest that subdisciplinary advances have led both to the opportunity and to the
      necessity to reintegrate knowledge into a new understanding of the whole
      organism. We present a conceptual framework for a modeling approach that
      addresses the functioning of organisms in an integrative way, incorporating
      elements from environments, populations, individuals, and intra-organismal
      dynamics such as physiology and behavior. To give substance to our conceptual
      framework, we provide a preliminary focal case study using phenotypic plasticity
      in the tooth morphology of snails in the genus Lacuna. We use this case study to
      illustrate ways in which questions about the evolution and ecology of organismal
      function intrinsically span all organizational levels. In this case, and in many
      others, quantitative approaches that integrate across mechanisms and scales can
      suggest new hypotheses about organismal function, and provide new tools to test
      those hypotheses. Integrative quantitative models also provide roadmaps for the
      large-scale collaborations among diverse disciplinary specialists that are needed
      to gain deeper insights into organismal function. 

PMID- 24861807
TI  - Lanthanide complexes containing 5-methyl-1,2,4-triazolo[1,5-a] pyrimidin-7(4H)
      one and their therapeutic potential to fight leishmaniasis and Chagas disease.
AB  - In the last years, numerous and significant advances in lanthanide coordination
      chemistry have been achieved. The unique chemical nature of these metal ions
      which is conferred by their f-electrons has led to a wide range of coordination
      compounds with interesting structural, physical and also biological properties.
      Consequently, lanthanide complexes have found applications mainly in catalysis,
      gas adsorption, photochemistry and as diagnostic tools. However, research on
      their therapeutic potential and the understanding of their mechanism of action is
      still taking its first steps, and there is a distinct lack of research in the
      parasitology field. In the present work, we describe the synthesis and physical
      properties of seven new lanthanide complexes with the anionic form of the
      bioactive ligand 5-methyl-1,2,4-triazolo[1,5-a]pyrimidin-7(4H)-one (HmtpO),
      namely [Ln(mtpO)3(H2O)6].9H2O (Ln=La(III), Nd(III), Eu(III), Gd(III), Tb(III),
      Dy(III) and Er(III)). In addition, results on the in vitro antiproliferative
      activity against Leishmania spp. and Trypanosoma cruzi are described. The high
      activity of the new compounds against parasite proliferation and their low
      cytotoxicity against reference host cell lines show a great potential of this
      type of compounds to become a new generation of highly effective and non-toxic
      antiparasitic agents to fight the so considered neglected diseases leishmaniasis
      and Chagas disease. 

PMID- 24861810
TI  - Caenorhabditis elegans: an old genetic model can learn new epigenetic tricks.
AB  - Gamete cells pass on information to the next generation via DNA sequence and also
      through epigenetic mechanisms such as small RNAs, DNA methylation, or chromatin
      modifications. Caenorhabditis elegans is a genetic model system that an enormous
      number of talented researchers have used to understand biological phenomenon and
      develop molecular tools that have ultimately led to paradigm-shifting ideas in
      biology. Thus, this model is well poised to further investigate the molecular
      mechanisms involved with epigenetic modifications and transgenerational
      epigenetic inheritance. The strengths of this model system include a historical
      wealth of information regarding genetics, development, germline function,
      chromosome biology, and the regulation of gene expression. Using this system, one
      can investigate the mechanisms involved with how the germline passes on heritable
      epigenetic information to subsequent generations. Here, we highlight aspects
      about the biology of C. elegans that make it amenable to epigenetic studies,
      highlight some recent findings in the field of epigenetics, and comment on how
      this system would be beneficial for future biological studies involving
      epigenetic processes. 

PMID- 24861812
TI  - Testing hypotheses in ecoimmunology using mixed models: disentangling
      hierarchical correlations.
AB  - Considerable research in ecoimmunology focuses on investigating variation in
      immune responses and linking this variation to physiological trade-offs,
      ecological traits, and environmental conditions. Variation in immune responses
      exists within and among individuals, among populations, and among taxonomic
      groupings. Understanding how variation and covariation are distributed and how
      they differ across these levels is necessary for drawing appropriate ecological
      and evolutionary inferences. Moreover, variation at the among-individual level
      directly connects to underlying quantitative genetic parameters. In order to
      fully understand immune responses in evolutionary and ecological contexts and to
      reveal phylogenetic constraints on evolution, statistical approaches must allow
      (co)variance to be partitioned among levels of individual, population, and
      phylogenetic organization (e.g., population, species, genera, and various higher
      taxa). Herein, we describe how multi-response mixed-effects models can be used to
      partition variation in immune responses among different hierarchical levels,
      specifically within-individuals, among-individuals, and among-species. We use
      simulated data to demonstrate that mixed models allow for proper partitioning of
      (co)variances. Importantly, these simulations also demonstrate that conventional
      statistical tools grossly misestimate relevant parameters, which urges caution in
      relating ecoimmunological hypotheses to existing empirical research. We conclude
      by discussing the advantages and caveats of a mixed-effects modeling approach. 

PMID- 24861813
TI  - Cytogenetic and morphologic approaches of hybrids from experimental crosses
      between Triatoma lenti Sherlock & Serafim, 1967 and T. sherlocki Papa et al.,
      2002 (Hemiptera: Reduviidae).
AB  - The reproductive capacity between Triatoma lenti and Triatoma sherlocki was
      observed in order to verify the fertility and viability of the offspring.
      Cytogenetic, morphological and morphometric approaches were used to analyze the
      differences that were inherited. Experimental crosses were performed in both
      directions. The fertility rate of the eggs in crosses involving T. sherlocki
      females was 65% and 90% in F1 and F2 offspring, respectively. In reciprocal
      crosses, it was 7% and 25% in F1 and F2 offspring, respectively. The cytogenetic
      analyses of the male meiotic process of the hybrids were performed using lacto
      acetic orcein, C-banding and Feulgen techniques. The male F1 offspring presented
      normal chromosome behavior, a finding that was similar to those reported in
      parental species. However, cytogenetic analysis of F2 offspring showed errors in
      chromosome pairing. This post-zygotic isolation, which prevents hybrids in
      nature, may represent the collapse of the hybrid. This phenomenon is due to a
      genetic dysregulation that occurs in the chromosomes of F1. The results were
      similar in the hybrids from both crosses. Morphological features, such as color
      and size of connexive and the presence of red-orange rings on the femora, were
      similar to T. sherlocki, while wins size was similar to T. lenti in F1 offspring.
      The eggshells showed characteristics that were similar to species of origin,
      whereas the median process of the pygophore resulted in intermediate
      characteristics in the F1 and a segregating pattern in F2 offspring. Geometric
      morphometric techniques used on the wings showed that both F1 and F2 offspring
      were similar to T. lenti. These studies on the reproductive capacity between T.
      lenti and T. sherlocki confirm that both species are evolutionarily closed;
      hence, they are included in the brasiliensis subcomplex. The extremely reduced
      fertility observed in the F2 hybrids confirmed the specific status of the species
      that were analyzed. 

PMID- 24861814
TI  - A decade of G3P[8] and G9P[8] rotaviruses in Brazil: epidemiology and
      evolutionary analyses.
AB  - This study aims to estimate the frequency of group A rotaviruses (RVA) infection
      with genotypes G3P[8] and G9P[8] in children that suffered from diarrheal disease
      (DD) between 2001 and 2011 in different Brazilian regions. In addition, the
      genetic diversity of G3P[8] and G9P[8] RVA strains recovered from vaccinated and
      non-vaccinated children was assessed. Laboratory-based RVA surveillance included
      15,115 cases of DD, and RVA was detected by enzyme immune-assay and/or
      polyacrylamide gel electrophoresis in 3357 (22%) samples. RVA was genotyped by
      the semi-nested RT-PCR and among RVA-positive samples, 100 (2.9%) were G3 (63
      G3P[8], 32 G3P not typed [NT], and 5 G3P[6]) and 378 (16.2%) were G9 (318 G9P[8],
      59 G9P[NT], and 1 G9P[6]). From the G3 and G9 positive samples, 16 and 12,
      respectively, were obtained from children aged 4-48months vaccinated with the
      monovalent vaccine (Rotarix(r), RV1). Phylogenetic analyses of the VP7 and VP8(*)
      encoding genes were performed for 26 G3P[8] and 48 G9P[8] strains. VP8(*)
      phylogenetic analysis revealed that all strains analyzed belonged to P[8] lineage
      III, whereas RV1 belongs to P[8]-I lineage. VP7 analysis revealed that all G3 and
      G9 strains belonged to G3-lineage III and G9-lineage III. The comparison of the
      VP7 and VP8(*) antigenic epitopes regions of Brazilian strains with RV1 strain
      revealed several amino acid changes. However, no particular differences among
      Brazilian strains detected before and after vaccine introduction were observed,
      or among strains detected from vaccinated and non-vaccinated children. Complete
      genome characterization of four G3P[8] and seven G9P[8] strains revealed a
      typical conserved human Wa-like genomic constellation. Changes in the genetic
      diversity of G3P[8] and G9P[8] RVA detected from 2001 to 2011 in Brazil seemed
      not be related to RV1 introduction in Brazil. 

PMID- 24861811
TI  - Epigenetics and nutritional environmental signals.
AB  - All terrestrial life is influenced by multi-directional flows of information
      about its environment, enabling malleable phenotypic change through signals,
      chemical processes, or various forms of energy that facilitate acclimatization.
      Billions of biological co-inhabitants of the earth, including all plants and
      animals, collectively make up a genetic/epigenetic ecosystem by which
      adaptation/survival (inputs and outputs) are highly interdependent on one
      another. As an ecosystem, the solar system, rotation of the planets, changes in
      sunlight, and gravitational pull influence cyclic epigenetic transitions and
      chromatin remodeling that constitute biological circadian rhythms controlling
      senescence. In humans, adverse environmental conditions such as poverty, stress,
      alcohol, malnutrition, exposure to pollutants generated from industrialization,
      man-made chemicals, and use of synthetic drugs can lead to maladaptive epigenetic
      related illnesses with disease-specific genes being atypically activated or
      silenced. Nutrition and dietary practices are one of the largest facets in
      epigenetic-related metabolism, where specific "epi-nutrients" can stabilize the
      genome, given established roles in DNA methylation, histone modification, and
      chromatin remodeling. Moreover, food-based "epi-bioactive" constituents may
      reverse maladaptive epigenetic patterns, not only prior to conception and during
      fetal/early postnatal development but also through adulthood. In summary, in
      contrast to a static genomic DNA structure, epigenetic changes are potentially
      reversible, raising the hope for therapeutic and/or dietary interventions that
      can reverse deleterious epigenetic programing as a means to prevent or treat
      major illnesses. 

PMID- 24861815
TI  - Characterization of G2P[4] rotavirus strains associated with increased detection
      in Australian states using the RotaTeq(r) vaccine during the 2010-2011
      surveillance period.
AB  - The introduction of rotavirus vaccines Rotarix(r) and RotaTeq(r) into the
      Australian National Immunisation Program in July 2007 has resulted in a dramatic
      decrease in the burden of rotavirus disease. G2P[4] strains became the dominant
      genotype Australia-wide during the 2010-2011 surveillance period and for the
      first time since vaccine introduction, a higher proportion were isolated in
      jurisdictions using RotaTeq(r) vaccine compared to locations using Rotarix(r).
      Phylogenetic analysis of the VP7 gene of 32 G2P[4] strains identified six genetic
      clusters, these distinct clusters were also observed in the VP4 gene for a subset
      of 12 strains. The whole genome was determined for a representative strain of
      clusters; A (RVA/Human-wt/AUS/SA066/2010/G2P[4]), B (RVA/Human
      wt/AUS/WAPC703/2010/G2P[4]), C (RVA/Human-wt/AUS/MON008/2010/G2P[4]) and E
      (RVA/Human-wt/AUS/RCH041/2010/G2P[4]). All of the strains possessed the
      archetypal DS-1 like genome constellation G2-P[4]-I2-R2-C2-M2-A2-N2-T2-E2-H2.
      Three of the strains, SA066, MON008 and WAPC703 clustered together and were
      distinct to RCH041 for all 11 genes. The VP7 genes of 31/32 of the strains
      characterized in this study possessed five conserved amino acid substitutions
      when compared to the G2 VP7 gene present in the RotaTeq(r) vaccine. Three of the
      substitutions were in the VP7 antigenic regions A and C, the substitutions A87T,
      D96N and S213D have been reported in the majority of G2P[4] strains circulating
      globally over the previous decade. These changes may have improved the ability of
      strains to circulate in settings of high vaccine use. 

PMID- 24861816
TI  - Prevalence of mutations in the antifolates resistance-associated genes (dhfr and
      dhps) in Plasmodium vivax parasites from Eastern and Central Sudan.
AB  - Plasmodium vivax is the most geographically widespread species, and its burden
      has been increasingly documented in Eastern and Central Sudan. P. vivax becomes
      the crucial challenge during elimination programs; thus an effective treatment is
      necessary to prevent the development and the spread of resistant parasites.
      Therefore, the main objective of the present study was to provide data on the
      prevalence of molecular markers in two genes (pvdhfr and pvdhps) associated with
      SP resistance after nine years of AS+SP deployment among P. vivax parasites from
      Eastern and Central Sudan using PCR-RFLP. During 2012-2013, a number of 66 blood
      spots were obtained on filter paper. The samples were collected before treatment
      from febrile patients who were microscopically positive for P. vivax, from three
      states in Eastern and Central Sudan (Gezira, Gedarif, and Kassala). Mutations
      were detected in three codons of pvdhfr (I13L, S58R, and S117N) and none in
      pvdhps. The majority of P. vivax parasites had double mutations (58R/117N, 58%)
      in dhfr gene, while all parasites were wild type in dhps gene. In addition,
      limited distinct haplotypes (n=4) were detected. In conclusion, the prevalence of
      mutations associated with SP resistance is low in Eastern and Central Sudan. Such
      information is necessary for guiding malaria control measures in the frame of
      Roll Back Malaria strategies for the elimination of malaria in the world. 

PMID- 24861817
TI  - Cell culture metabolomics in the diagnosis of lung cancer-the influence of cell
      culture conditions.
AB  - Lung cancer is the leading cause of cancer deaths. Unfortunately, lung cancer is
      often diagnosed only when it becomes symptomatic or at an advanced stage when few
      treatment options are available. Hence, a diagnostic test suitable for screening
      widespread populations is required to enable earlier diagnosis. Analysis of
      exhaled breath provides a non-invasive method for early detection of lung cancer.
      Analysis of volatile organic compounds (VOCs) by various mass spectral techniques
      has identified potential biomarkers of disease. Nevertheless, the metabolic
      origins and the disease specificity of VOCs need further elucidation. Cell
      culture metabolomics can be used as a bottom-up approach to identify biomarkers
      of pathological conditions and can also be used to study the metabolic pathways
      that produce such compounds. This paper summarizes the current knowledge of lung
      cancer biomarkers in exhaled breath and emphasizes the critical role of cell
      culture conditions in determining the VOCs produced in vitro. Hypoxic culture
      conditions more closely mimic the conditions of cancer cell growth in vivo. We
      propose that since hypoxia influences cell metabolism and so potentially the VOCs
      that the cancer cells produce, the cell culture metabolomics projects should
      consider culturing cancer cells in hypoxic conditions. 

PMID- 24861818
TI  - The Lactococcus lactis plasmidome: much learnt, yet still lots to discover.
AB  - Lactococcus lactis is used extensively worldwide for the production of a variety
      of fermented dairy products. The ability of L. lactis to successfully grow and
      acidify milk has long been known to be reliant on a number of plasmid-encoded
      traits. The recent availability of low-cost, high-quality genome sequencing, and
      the quest for novel, technologically desirable characteristics, such as novel
      flavour development and increased stress tolerance, has led to a steady increase
      in the number of available lactococcal plasmid sequences. We will review both
      well-known and very recent discoveries regarding plasmid-encoded traits of
      biotechnological significance. The acquired lactococcal plasmid sequence
      information has in recent years progressed our understanding of the origin of
      lactococcal dairy starter cultures. Salient points on the acquisition and
      evolution of lactococcal plasmids will be discussed in this review, as well as
      prospects of finding novel plasmid-encoded functions. 

PMID- 24861819
TI  - Child Maltreatment Fatalities Related to Inadequate Caregiver Supervision.
AB  - More than 1,500 children died in the United States in 2011 due to child
      maltreatment. A substantial portion of these deaths were due to neglect. Previous
      research has found that a large percentage of child neglect cases involve
      supervisory neglect; however, the role of inadequate caregiver supervision (ICS)
      in child maltreatment deaths is unknown. The present study reviewed files from
      the Child Death Review Board in the state of Oklahoma for the years 2000 to 2003
      to examine (a) how many deaths were due to inadequate caregiver supervision and
      (b) which child, caregiver, family, alleged perpetrator, and incident
      characteristics predicted risk for death related to ICS. Results indicated that
      almost half of the child maltreatment deaths were related to ICS. Older children
      and those living in homes with greater numbers of children were more likely to
      die from causes related to ICS. In addition, the alleged perpetrators of deaths
      related to ICS were more likely to be biological parents than alleged
      perpetrators of non-ICS-related deaths. These findings suggest that interventions
      to assist caregivers in providing appropriate levels of supervision for their
      children may be important for reducing children's risk for death.

PMID- 24861820
TI  - Psychosocial assessment of candidates and risk classification of patients
      considered for durable mechanical circulatory support.
AB  - BACKGROUND: The psychosocial assessment of candidates for transplantation (PACT),
      developed to assess candidates for heart transplant, has not been routinely used
      to assess left ventricular assist device (LVAD) candidacy. We examined the
      efficacy of the PACT to assess psychosocial outcomes in LVAD patients. METHODS:
      We reviewed patients who received LVAD implants between June 2006 and April 2011
      and retrospectively applied the PACT. We determined the accuracy of identifying
      social success with the PACT and revised domains to reflect criteria influencing
      social success for LVAD patients. RESULTS: Forty-eight patients (72% men, 44% non
      white, 50.4 years old) were divided into high-scoring and low-scoring groups.
      Nine patients with low PACT scores were falsely categorized as high-risk, whereas
      4 with high scores had poor social outcomes. The score had a high positive
      predictive value (0.86) but low negative-predictive value (0.31). The PACT was
      revised (modified [m]PACT) to measure indicators, such as social support and
      understanding of care requirements, identified to more closely affect LVAD
      outcome. The mPACT exhibited improved accuracy. A reclassification table was
      developed, and the net reclassification index was 0.32. The percentage of
      patients incorrectly classified for social risk decreased from 27% with the PACT
      to 8% with the mPACT. Patients with higher mPACT scores had decreased 30-day
      readmission rates (26% vs 67%, p = 0.045) after device implantation. CONCLUSIONS:
      By emphasizing social support, psychologic health, lifestyle factors, and device
      understanding, the mPACT showed improved performance in risk-stratifying
      candidates for LVAD therapy. Prospective validation is warranted.

PMID- 24861821
TI  - Outcomes of third heart transplants in pediatric and young adult patients:
      analysis of the United Network for Organ Sharing database.
AB  - BACKGROUND: Repeat heart transplantation (re-HTx) is standard practice in many
      pediatric centers. There are limited data available on outcomes of third HTx
      after failure of a second graft. We sought to compare outcomes of third HTx in
      pediatric and young adult patients with outcomes of second HTx in comparable
      recipients. METHODS: All recipients of a third HTx in whom the primary HTx
      occurred before 21 years of age were identified in the United Network for Organ
      Sharing database (1985 to 2011) and matched 1:3 with a control group of second
      HTx patients by age, era and re-HTx indication. Outcomes including survival,
      rejection and cardiac allograft vasculopathy (CAV) were compared between groups.
      RESULTS: There was no difference between third HTx patients (n = 27) and control
      second HTx patients (n = 79) with respect to survival (76% vs 80% at 1 year, 62%
      vs 58% at 5 years and 53% vs 34% at 10 years, p = 0.75), early (<1 year from HTx)
      rejection (33.3% vs 44.3%, p = 0.32) or CAV (14.8% vs 30.4%, p = 0.11). Factors
      associated with non-survival in third HTx patients included mechanical
      ventilation at listing or HTx, extracorporeal membrane oxygenation support at
      listing or HTx, and elevated serum bilirubin at HTx. CONCLUSIONS: Outcomes among
      recipients of a third HTx are similar to those with a second HTx in matched
      patients, with no difference in short- or long-term survival and comparable rates
      of early rejection and CAV. Although the occurrence of a third HTx remains
      relatively rare in the USA, consideration of a third HTx appears reasonable in
      appropriately selected patients.

PMID- 24861822
TI  - Wurster's Blue-type cation radicals framed in a 5,10-dihydrobenzo[a]indolo[2,3
      c]carbazole (BIC) skeleton: dual electrochromism with drastic changes in
      UV/Vis/NIR and fluorescence.
AB  - Electron-donating dihydrobenzindolocarbazoles (BICs) 1 a-c, which adopt planar
      disk-shaped geometries, were prepared by gold(I)-catalyzed cyclization as a key
      step. Due to the presence of a 1,4-phenylenediamine (PD) moiety in the framework,
      they undergo reversible one-electron oxidation to the corresponding Wurster's
      Blue (WB)-type species that exhibits NIR absorptions up to lambda=1200 nm. In the
      case of the N,N'-dimethyl derivative, cation radical 1 c(+.) is stable enough to
      be isolated as a salt and X-ray analysis indicated paraquinoid-type bond
      alternation in the WB core unit, whereas the bond lengths in the peripheral
      benzene rings are identical to those in the neutral donor. Upon electrochemical
      interconversion, the redox pairs of 1 a-c and 1 a-c(+.) exhibited an
      electrochromic response in the UV/Vis/NIR region, which was accompanied by a
      drastic change in the fluorescence spectrum because only neutral donors 1 a-c are
      highly emissive (Phi(F) : 0.7-0.8).

PMID- 24861823
TI  - Conjugated-polyelectrolyte-based polyprodrug: targeted and image-guided
      photodynamic and chemotherapy with on-demand drug release upon irradiation with a
      single light source.
AB  - Nanomaterials that combine diagnostic and therapeutic functions within a single
      nanoplatform are highly desirable for molecular medicine. Herein we report a
      novel theranostic platform based on a conjugated-polyelectrolyte (CPE)
      polyprodrug that contains functionality for image, chemo- and photodynamic
      therapy (PDT), and on-demand drug release upon irradiation with a single light
      source. Specifically, the PEGylated CPE serves as a photosensitizer and a
      carrier, and is covalently conjugated to doxorubicin through a linker that can be
      cleaved by reactive oxygen species (ROS). Under appropriate light irradiation,
      the CPE can generate ROS, not only for PDT, but also for on-demand drug release
      and chemotherapy. This nanoplatform will offer on-demand PDT and chemotherapy
      with drug release triggered by one light switch, which has great potential in
      cancer treatment. 

PMID- 24861825
TI  - Li-O(2) battery based on highly efficient Sb-doped tin oxide supported Ru
      nanoparticles.
AB  - Novel cathodes based on Sb-doped tin oxide (STO)-supported Ru particles enable Li
      O2 batteries to be operated below 4.0 V, which is of crucial importance for the
      realization of rechargeable Li-O2 batteries, and to deliver a high specific
      capacity of 750 mA h g(-1) even after 50 discharge-charge cycles at 0.1 mA cm(-2)
      . 

PMID- 24861824
TI  - Increase in accumulation of strontium-90 in the maternal skeleton during
      pregnancy and lactation: analysis of the Techa River data.
AB  - The unique contamination of the Techa River (Southern Urals, Russia) in the 1950s
      by long-lived (90)Sr allows investigation of the accumulation of bone-seeking
      elements in humans. This study is based on information compiled at the Urals
      Research Center for Radiation Medicine (Chelyabinsk, Russia) over a long period
      of time. It includes the results of in vivo measurements of (90)Sr-body burden
      with a whole body counter (WBC), data on personal medical examinations and
      residence and family histories. Data on 185 women from two Techa riverside
      villages Muslyumovo and Brodokalmak were selected. The settlements differ in
      terms of (90)Sr diet intake (higher in Muslyumovo than in Brodokalmak) and
      ethnicity (residents were mainly Slavs in Brodokalmak and Turkic in Muslyumovo).
      Results of a total of 555 WBC measurements performed in 1974-1997 were available
      for the women studied; maximum measured values reached 40 kBq/body. The women
      from each settlement were subdivided into three groups according to their
      childbearing history: pregnancy and lactation occurred (1) during the period of
      maximal (90)Sr intake (1950-1951); (2) after the period of maximal intake and (3)
      before this period or women who were childless. An increase was found in
      accumulation of (90)Sr in maternal skeleton during pregnancy and lactation (group
      1) by a factor of 1.5-2 in comparison with non-pregnant, non-lactating women.
      This result was found in both Muslyumovo and Brodokalmak samples. An increase in
      accumulation of toxic elements in pregnant/lactating women is associated with
      increased radiation/toxic doses and risk for the women's health. 

PMID- 24861826
TI  - The use of a lateral wedge insole to reduce knee loading when ascending and
      descending stairs in medial knee osteoarthritis patients.
AB  - BACKGROUND: Stair climbing is a challenging task to the elderly being the task
      with the first complaint in patients with mild to moderate knee osteoarthritis.
      Stair climbing results in around six times more compressive load transmitted
      through the knee joint than walking on level ground. The purpose of this study
      was to assess whether lateral wedge insoles would reduce medial compartment knee
      loading when ascending and descending stairs in patients with medial knee
      osteoarthritis. METHODS: Eight patients with medial knee osteoarthritis were
      tested in random order with and without a pair of 5 degrees  off-the-shelf
      lateral wedge insoles for two separate activities (stair ascent and stair
      descent). Kinematic and kinetic data were collected for the lower extremity using
      a sixteen camera motion capture system and two force plates. Primary outcome
      measures were the external knee adduction moment and the knee adduction angular
      impulse. FINDINGS: During stair ascent and descent, lateral wedge insoles
      significantly (P<0.05) reduced the 1st peak external knee adduction moment in
      early stance (ascent 6.8%, descent 8.4%), the trough in mid stance (ascent 13%,
      descent 10.7%), 2nd peak in the late stance (ascent 15%, descent 8.3%) and the
      knee adduction angular impulse compared to the control (standard shoe) with large
      effect sizes (0.75-0.95). INTERPRETATION: In this first study on stairs, lateral
      wedge insoles consistently reduced the overall magnitude of medial compartment
      loading during stair ascent and descent. Further research is needed to determine
      the relationship of this with clinical results when ascending and descending
      stairs with lateral wedge insoles.

PMID- 24861827
TI  - Effects of immediate vs. delayed massage-like loading on skeletal muscle
      viscoelastic properties following eccentric exercise.
AB  - BACKGROUND: This study compared immediate versus delayed massage-like compressive
      loading on skeletal muscle viscoelastic properties following eccentric exercise.
      METHODS: Eighteen rabbits were surgically instrumented with peroneal nerve cuffs
      for stimulation of the tibialis anterior muscle. Rabbits were randomly assigned
      to a massage loading protocol applied immediately post exercise (n=6), commencing
      48h post exercise (n=6), or exercised no-massage control (n=6). Viscoelastic
      properties were evaluated in vivo by performing a stress-relaxation test pre- and
      post-exercise and daily pre- and post-massage for four consecutive days of
      massage loading. A quasi-linear viscoelastic approach modeled the instantaneous
      elastic response (AG0), fast (g1(p)) and slow (g2(p)) relaxation coefficients,
      and the corresponding relaxation time constants tau1 and tau2. FINDINGS: Exercise
      increased AG0 in all groups (P<0.05). After adjusting for the three multiple
      comparisons, recovery of AG0 was not significant in the immediate (P=0.021) or
      delayed (P=0.048) group compared to the control group following four days of
      massage. However, within-day (pre- to post-massage) analysis revealed a decrease
      in AG0 in both massage groups. Following exercise, g1(p) increased and g2(p) and
      tau1 decreased for all groups (P<0.05). Exercise had no effect on tau2 (P>0.05).
      After four days of massage, there was no significant recovery of the relaxation
      parameters for either massage loading group compared to the control group.
      INTERPRETATION: Our findings suggest that massage loading following eccentric
      exercise has a greater effect on reducing muscle stiffness, estimated by AG0,
      within-day rather than affecting recovery over multiple days. Massage loading
      also has little effect on the relaxation response.

PMID- 24861829
TI  - Modified carpentier's technique for Ebstein's anomaly repair.
AB  - OBJECTIVES: This retrospective study assesses the outcomes of a modified
      Carpentier's technique for Ebstein's anomaly repair in respect to functional and
      anatomical recovery of the right ventricle and tricuspid valve. PATIENTS AND
      METHODS: From August 2005 to December 2010, 52 patients with Ebstein's anomaly
      were operated in Hanoi Heart Hospital, Vietnam using the modified Carpentier's
      technique: (1) extensive mobilization of the tricuspid leaflet by detachment of
      the posterior, septal, and the adjacent part of the anterior leaflet; (2)
      longitudinal plication of the atrialized chamber and the right atrium to
      reconstruct the right ventricle and reduce the size of the dilated right atrium;
      (3) relocation of the anterior, posterior, and septal leaflets to the normal
      tricuspid annulus; and (4) tricuspid annuloplasty. RESULTS: Mean age was 20 years
      (3-49 years). Tricuspid regurgitation (in four-grade scale) was reduced from 3.72
      +/- 0.48 to 1.56 +/- 0.48 (p < 0.01) and NYHA functional class was improved from
      2.53 +/- 0.53 to 1.14 +/- 0.35 (p < 0.01). There was one hospital death (1, 95%)
      due to postoperative severe bleeding. There was no long-term mortality or
      reoperation after 42.4 months (17-81 months) follow-up. CONCLUSION: Satisfactory
      outcomes can be achieved with complete repair of Ebstein's anomaly using the
      modified Carpentier's technique.

PMID- 24861830
TI  - Oscillations, networks, and their development: MEG connectivity changes with age.
AB  - Magnetoencephalographic (MEG) investigations of inter-regional amplitude
      correlations have yielded new insights into the organization and neurophysiology
      of resting-state networks (RSNs) first identified using fMRI. Inter-regional MEG
      amplitude correlations in adult RSNs have been shown to be most prominent in
      alpha and beta frequency ranges and to express strong congruence with RSN
      topologies found using fMRI. Despite such advances, little is known about how
      oscillatory connectivity in RSNs develops throughout childhood and adolescence.
      This study used a novel fMRI-guided MEG approach to investigate the maturation of
      resting-state amplitude correlations in physiologically relevant frequency ranges
      within and among six RSNs in 59 participants, aged 6-34 years. We report age
      related increases in inter-regional amplitude correlations that were largest in
      alpha and beta frequency bands. In contrast to fMRI reports, these changes were
      observed both within and between the various RSNs analyzed. Our results provide
      the first evidence of developmental changes in spontaneous neurophysiological
      connectivity in source-resolved RSNs, which indicate increasing integration
      within and among intrinsic functional brain networks throughout childhood,
      adolescence, and early adulthood.

PMID- 24861828
TI  - Low-dose estradiol and the serotonin-norepinephrine reuptake inhibitor
      venlafaxine for vasomotor symptoms: a randomized clinical trial.
AB  - IMPORTANCE: Estrogen therapy is the gold standard treatment for hot flashes and
      night sweats, but some women are unable or unwilling to use it because of
      associated risks. The serotonin-norepinephrine reuptake inhibitor venlafaxine
      hydrochloride is used widely as a nonhormonal treatment. While the clinical
      impression is that serotonin-norepinephrine reuptake inhibitors are less
      effective than estrogen, these medications have not been simultaneously evaluated
      in one clinical trial to date. OBJECTIVE: To determine the efficacy and
      tolerability of low-dose oral 17beta-estradiol and low-dose venlafaxine extended
      release in alleviating vasomotor symptoms (VMS). DESIGN, SETTING, AND
      PARTICIPANTS: In total, 339 perimenopausal and postmenopausal women with at least
      2 bothersome VMS per day (mean, 8.1 per day) were recruited from the community to
      MsFLASH (Menopause Strategies: Finding Lasting Answers for Symptoms and Health)
      clinical network sites between December 5, 2011, and October 15, 2012.
      INTERVENTIONS: Participants were randomized to double-blind treatment with low
      dose oral 17beta-estradiol (0.5 mg/d) (n = 97), low-dose venlafaxine
      hydrochloride extended release (75 mg/d) (n = 96), or placebo (n = 146) for 8
      weeks. MAIN OUTCOMES AND MEASURES: The primary outcome was the mean daily
      frequency of VMS after 8 weeks of treatment. Secondary outcomes were VMS
      severity, bother, and interference with daily life. Intent-to-treat analyses
      compared the change in VMS frequency between each active intervention and placebo
      and between the 2 active treatments. RESULTS: Compared with baseline, the mean
      VMS frequency at week 8 decreased to 3.9 (95% CI, 2.9-4.9) VMS per day (52.9%
      reduction) in the estradiol group, to 4.4 (95% CI, 3.5-5.3) VMS per day (47.6%
      reduction) in the venlafaxine group, and to 5.5 (95% CI, 4.7-6.3) VMS per day
      (28.6% reduction) in the placebo group. Estradiol reduced the frequency of
      symptoms by 2.3 more per day than placebo (P < .001), and venlafaxine reduced the
      frequency of symptoms by 1.8 more per day than placebo (P = .005). The results
      were consistent for VMS severity, bother, and interference. Low-dose estradiol
      reduced the frequency of symptoms by 0.6 more per day than venlafaxine (P = .09).
      Treatment satisfaction was highest (70.3%) for estradiol (P < .001 vs placebo),
      lowest (38.4%) for placebo, and intermediate (51.1%) for venlafaxine (P = .06 vs
      placebo). Both interventions were well tolerated. CONCLUSIONS AND RELEVANCE: Low
      dose oral estradiol and venlafaxine are effective treatments for VMS in women
      during midlife. While the efficacy of low-dose estradiol may be slightly superior
      to that of venlafaxine, the difference is small and of uncertain clinical
      relevance. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01418209.

PMID- 24861831
TI  - Angiocentric glioma: a report of nine new cases, including four with atypical
      histological features.
AB  - AIMS: Angiocentric glioma (AG) is a rare, slow-growing tumour of the central
      nervous system. It is often associated with refractory epilepsy and occurs most
      commonly in children and young adults. We herein report nine cases of AG,
      including four with atypical histological findings. METHODS: The clinical data
      and clinicopathological findings of nine cases with AG histological features were
      described. RESULTS: All nine patients had a history of refractory epilepsy with a
      mean history of 4.4 years and a median age of 17.6 years at surgery. The AG
      lesions were located in the superficial cerebrocortical region. Histological
      examination of these cases revealed characteristic structural features of AG,
      including bipolar spindle-shaped cells with an angiocentric growth pattern.
      However, four cases also exhibited atypical histological features: one had
      astroblastoma-like characteristics, two had a distinct cystic region with an
      onion-like structure and myxoid changes, and the other one had a region involving
      many abnormal neurones reminiscent to ganglioglioma. All were positive for glial
      fibrillary acidic protein and vimentin. Eight cases were positive for epithelial
      membrane antigen (EMA), with a dot-like staining pattern. A diffuse D2-40
      staining was visible in these cases, with two having similar staining pattern to
      EMA. All cases were immunonegative for BRAF V600E and isocitrate dehydrogenase-1
      R132H mutations. CONCLUSIONS: Our results demonstrate that atypical histological
      features can be present in AG. A collection of more cases and further molecular
      analyses are required to confirm our findings.

PMID- 24861832
TI  - DNA polymerase epsilon and its roles in genome stability.
AB  - DNA Polymerase Epsilon (Pol epsilon) is one of three DNA Polymerases (along with
      Pol delta and Pol alpha) required for nuclear DNA replication in eukaryotes. Pol
      epsilon is comprised of four subunits, the largest of which is encoded by the
      POLE gene and contains the catalytic polymerase and exonuclease activities. The
      3'-5' exonuclease proofreading activity is able to correct DNA synthesis errors
      and helps protect against genome instability. Recent cancer genome sequencing
      efforts have shown that 3% of colorectal and 7% of endometrial cancers contain
      mutations within the exonuclease domain of POLE and are associated with
      significantly elevated levels of single nucleotide substitutions (15-500 per Mb)
      and microsatellite stability. POLE mutations have also been found in other tumor
      types, though at lower frequency, suggesting roles in tumorigenesis more broadly
      in different tissue types. In addition to its proofreading activity, Pol epsilon
      contributes to genome stability through multiple mechanisms that are discussed in
      this review.

PMID- 24861833
TI  - Can moxibustion, an ancient treatment modality, be evaluated in a double-blind
      randomized controlled trial? - a narrative review.
AB  - For thousands of years, moxibustion has been used for various diseases in China
      and other Asian countries. Despite the recent surge in Chinese herbal studies,
      few randomized controlled trials have been conducted on this modality, possibly
      due to the lacking of suitable double blinding methodology. This is a review of
      extant sham moxa devices and an introduction to a recently developed device that
      needs further validation. 

PMID- 24861834
TI  - Efficacy of polyphenolic ingredients of Chinese herbs in treating dyslipidemia of
      metabolic syndromes.
AB  - There is an increasing interest and popularity of Chinese herbal medicine
      worldwide, which is accompanied by increasing concerns about its effectiveness
      and potential toxicity. Several ingredients, such as polyphenolic compounds
      berberine, flavonoids, and curcumin, have been studied extensively by using
      various animal models. Effectiveness of treatment and amelioration of metabolic
      syndromes, including insulin resistance and dyslipidemia, has been demonstrated.
      This review summarizes the major checkpoints and contributing factors in
      regulation of exogenous and endogenous lipid metabolism, with particular emphasis
      centered on triglyceride-rich and cholesterol-rich lipoproteins. Available
      experimental evidence demonstrating the lipid-lowering effect of berberine,
      flavonoids and curcumin in cell culture and animal models is compiled, and the
      strengths and shortcomings of experimental designs in these studies are
      discussed. 

PMID- 24861835
TI  - Advances in mesenchymal stem cells combined with traditional Chinese medicine
      therapy for liver fibrosis.
AB  - Liver fibrosis is a primary cause of liver cirrhosis, and even hepatocarcinoma.
      Recently, the usage of mesenchymal stem cells (MSCs) has been investigated to
      improve liver fibrosis. It has been reported that the differentiation,
      proliferation and migration of MSCs can be regulated by traditional Chinese
      medicine treatment; however, the mechanisms are still unclear. In this article,
      the authors review the characteristics of MSCs such as multidirectional
      differentiation and homing, and its application in animal experiments and
      clinical trials. The authors also list areas that need further investigation,
      andlook at the future prospects of clinical application of MSCs. 

PMID- 24861836
TI  - Heart rate variability and the influence of craniosacral therapy on autonomous
      nervous system regulation in persons with subjective discomforts: a pilot study.
AB  - BACKGROUND: Subjective discomforts in a preclinical range are often due to
      imbalanced autonomic nervous system activity, which is a focus of craniosacral
      therapy. OBJECTIVE: The aim of this work was to determine any changes in heart
      rate variability (HRV) in a study on craniosacral therapy. DESIGN, SETTING,
      PARTICIPANTS AND INTERVENTIONS: This is a quasi-experimental (controlled) study
      with cross-over design. In a private practice, measurements were performed on 31
      patients with subjective discomforts before and after a control and an
      intervention period. HRV was determined using a device that requires a measuring
      time of 140 s and electrode contact only with the fingertips. Main PRIMARY
      OUTCOME MEASURES: HRV change under the influence of a defined one-time
      intervention (test intervention) with craniosacral therapy versus control
      (defined rest period). RESULTS: Standard deviation of all RR-intervals (ms) and
      total power of RR-interval variability in the frequency range (ms(2)) were
      together interpreted as an indicator of test subjects' autonomic nervous activity
      and as a measure of their ability to cope with demands on their health. Neither
      of these parameters increased during the control period (P>0.05), whereas during
      the test intervention period there was an increase in both (P<0.05, P<0.01).
      Nevertheless, interactions between treatment and the increase were statistically
      not significant (P>0.05). No changes were observed in the low frequency/high
      frequency ratio (sympathetic-vagal balance) in the course of the control or the
      test intervention period (P>0.05). CONCLUSION: Craniosacral treatment had a
      favourable effect on autonomic nervous activity. This in itself is an interesting
      result, but further research will be needed to distinguish specific effects of
      craniosacral therapy technique from less specific therapist-client interaction
      effects.

PMID- 24861837
TI  - Chemotherapy in conjunction with traditional Chinese medicine for survival of
      elderly patients with advanced non-small-cell lung cancer: protocol for a
      randomized double-blind controlled trial.
AB  - BACKGROUND: Traditional Chinese medicine (TCM) is considered an important
      complementary therapy with beneficial effects for cancer patients. Elderly
      patients with non-small-cell lung cancer (NSCLC) are a complex patient group with
      increasing co-morbidity and shrinking physiological reserve, and may derive
      substantial benefit from the supportive aspects of TCM. Researchers from Shanghai
      Longhua Hospital found that qi and yin deficiency is a common syndrome in
      patients with stage III or IV lung cancer. This project was designed to study the
      combination of single-agent chemotherapy with TCM methods of benefiting qi and
      yin in elderly patients with advanced NSCLC. METHODS AND DESIGN: This is a double
      blind controlled, multi-center, and prospective study with randomly selected
      participants from elderly NSCLC patients in China. Seventy-six patients who meet
      the inclusion criteria will be allocated into two groups, which will receive
      treatments of 3-week single-agent chemotherapy with TCM or placebo for four
      cycles. Progression-free survival (PFS) is the primary end point, and the
      secondary end points are overall survival, objective response rate, time-to
      progression, and quality of life (EORTC QLQ-LC43, and TCM syndrome score).
      Meanwhile, other end points such as toxicity, side effects and safety of the
      treatments will be assessed. DISCUSSION: Results from this study may provide
      evidence on the effectiveness, and parameters for the usage of single-agent
      chemotherapy combined with or without TCM on PFS of elderly patients with NSCLC.
      TRIAL REGISTRATION: ClinicalTrials.gov. (Identifier: NCT01780181).

PMID- 24861838
TI  - Chinese integrative medicine: inclusion of a Chinese medicine programme in a
      conventional medical institute.
AB  - To meet community demands with optimal Chinese and conventional medical
      treatment, the University of Hong Kong is promoting integrative medicine by
      developing Chinese medicine programmes that train students of both Western and
      Chinese medicine. The programmes emphasize multi-disciplinary training and
      interaction between the two therapeutic approaches, enabling students to
      establish reliable, consistent, and respectful mutual cooperation in their future
      careers. 

PMID- 24861840
TI  - Comparison of pathogenicities and nucleotide changes between porcine and bovine
      reassortant rotavirus strains possessing the same genotype constellation in
      piglets and calves.
AB  - Although reassortment is one of the most important characteristics of group A
      rotavirus (RVA) evolution, the host range restriction and/or virulence of
      reassortant RVAs remain largely unknown. The porcine 174-1 strain isolated from a
      diarrheic piglet was identified as a reassortant strain, harboring the same
      genotype constellation as the previously characterized bovine strain KJ56-1.
      Owing to its same genotype constellation, the pathogenicity of the porcine strain
      174-1 in piglets and calves was examined for comparison with that of the bovine
      reassortant KJ56-1 strain, whose pathogenicity has already been demonstrated in
      piglets and calves. The porcine 174-1 strain induced diarrhea and
      histopathological changes in the small intestine of piglets and calves, whereas
      KJ56-1 had been reported to be virulent only in piglets, but not in calves.
      Therefore, full genomic sequences of 174-1 and KJ56-1 strains were analyzed to
      determine whether specific mutations might be associated with clinical and
      pathological phenotypes. Sequence alignment between the 174-1 and KJ56-1 strains
      detected one nucleotide substitution at the 3' untranslated region of the NSP3
      gene and 16 amino acid substitutions at the VP7, VP4, VP1, VP3, NSP1 and NSP4
      genes. These mutations may be critical molecular determinants for different
      virulence and/or pathogenicity of each strain. This study presents new insights
      into the host range restriction and/or virulence of RVAs. 

PMID- 24861841
TI  - Canis lupus familiaris involved in the transmission of pathogenic Yersinia spp.
      in China.
AB  - To investigate canines carrying pathogens associated with human illness, we
      studied their roles in transmitting and maintaining pathogenic Yersinia spp. We
      examined different ecological landscapes in China for the distribution of
      pathogenic Yersinia spp. in Canis lupus familiaris, the domestic dog. The highest
      number of pathogenic Yersinia enterocolitica was shown from the tonsils (6.30%),
      followed by rectal swabs (3.63%) and feces (1.23%). Strains isolated from plague
      free areas for C. lupus familiaris, local pig and diarrhea patients shared the
      same pulsed-field gel electrophoresis (PFGE) pattern, indicating they may be from
      the same clone and the close transmission source of pathogenic Y. enterocolitica
      infections in these areas. Among 226 dogs serum samples collected from natural
      plague areas of Yersinia pestis in Gansu and Qinghai Provinces, 49 were positive
      for F1 antibody, while the serum samples collected from plague free areas were
      all negative, suggested a potential public health risk following exposure to
      dogs. No Y. enterocolitica or Yersinia pseudotuberculosis was isolated from
      canine rectal swabs in natural plague areas. Therefore, pathogenic Yersinia spp.
      may be regionally distributed in China. 

PMID- 24861842
TI  - Escherichia fergusonii.
AB  - Escherichia fergusonii was introduced in the genus Escherichia almost 65 years
      later than Escherichia coli after which the genus was named. From then (1985)
      onwards mainly case reports on E. fergusonii associated with disease in
      individuals of veterinary or human origin have been reported and only very few
      more extensive studies became available. This has resulted in very fragmented
      knowledge on this organism. The aim of this manuscript is to give an overview of
      what is known on E. fergusonii today and to stimulate more research on this
      organism so that better insight can be obtained in the role that E. fergusonii
      plays in human and animal infections. 

PMID- 24861843
TI  - Molecular imaging using nanoparticle quenchers of Cerenkov luminescence.
AB  - Cerenkov luminescence (CL) imaging is an emerging technique that collects the
      visible photons produced by radioisotopes. Here, molecular imaging strategies are
      investigated that switch the CL signal off. The noninvasive molecularly specific
      detection of cancer is demonstrated utilizing a combination of clinically
      approved agents, and their analogues. CL is modulated in vitro in a dose
      dependent manner using approved small molecules (Lymphazurin), as well as the
      clinically approved Feraheme and other preclinical superparamagnetic iron oxide
      nanoparticles (SPIO). To evaluate the quenching of CL in vivo, two strategies are
      pursued. [(18) F]-FDG is imaged by PET and CL in tumors prior to and following
      accumulation of nanoparticles. Initially, non-targeted particles are administered
      to mice bearing tumors in order to attenuate CL. For targeted imaging, a dual
      tumor model (expressing the human somatostatin receptor subtype-2 (hSSTr2) and a
      control negative cell line) is used. Targeting hSSTr2 with octreotate-conjugated
      SPIO, quenched CL enabling non-invasive distinction between tumors' molecular
      expression profiles is demonstrated. In this work, the quenching of Cerenkov
      emissions is demonstrated in several proof of principle models using a
      combination of approved agents and nanoparticle platforms to provide disease
      relevant information including tumor vascularity and specific antigen expression.

PMID- 24861845
TI  - Internal bacterial colonization of implants: association with peri-implant bone
      loss.
AB  - OBJECTIVES: The aim of the present longitudinal study was to investigate
      bacterial colonization of the internal implant cavity and to evaluate a possible
      association with peri-implant bone loss. METHODS: A total of 264 paper point
      samples were harvested from the intra-implant cavity of 66 implants in 26
      patients immediately following implant insertion and after 3, 4, and 12 months.
      Samples were evaluated for Aggregatibacter actinomycetemcomitans, Fusobacterium
      nucleatum, Porphyromonas gingivalis, Prevotella intermedia, Treponema denticola,
      and Tannerella forsythia as well as total bacterial counts by real-time PCR. Bone
      loss was evaluated on standardized radiographs up to 25 months after implant
      insertion. For the statistical analysis of the data, mixed effects models were
      fitted. RESULTS: There was an increase in the frequency of detection as well as
      in the mean counts of the selected bacteria over time. The evaluation of the
      target bacteria revealed a significant association of Pr. intermedia at 4 and 12
      months with peri-implant bone loss at 25 months (4 months: P = 0.009; 12 months:
      P = 0.021). CONCLUSIONS: The present study could demonstrate a progressive
      colonization by periodontopathogenic bacteria in the internal cavities of two
      piece implants. The results suggest that internal colonization with Pr.
      intermedia was associated with peri-implant bone loss.

PMID- 24861844
TI  - Spatial differences and temporal changes in illicit drug use in Europe quantified
      by wastewater analysis.
AB  - AIMS: To perform wastewater analyses to assess spatial differences and temporal
      changes of illicit drug use in a large European population. DESIGN: Analyses of
      raw wastewater over a 1-week period in 2012 and 2013. SETTING AND PARTICIPANTS:
      Catchment areas of wastewater treatment plants (WWTPs) across Europe, as follows:
      2012: 25 WWTPs in 11 countries (23 cities, total population 11.50 million); 2013:
      47 WWTPs in 21 countries (42 cities, total population 24.74 million).
      MEASUREMENTS: Excretion products of five illicit drugs (cocaine, amphetamine,
      ecstasy, methamphetamine, cannabis) were quantified in wastewater samples using
      methods based on liquid chromatography coupled to mass spectrometry. FINDINGS:
      Spatial differences were assessed and confirmed to vary greatly across European
      metropolitan areas. In general, results were in agreement with traditional
      surveillance data, where available. While temporal changes were substantial in
      individual cities and years (P ranging from insignificant to <10(-3) ), overall
      means were relatively stable. The overall mean of methamphetamine was an
      exception (apparent decline in 2012), as it was influenced mainly by four cities.
      CONCLUSIONS: Wastewater analysis performed across Europe provides complementary
      evidence on illicit drug consumption and generally concurs with traditional
      surveillance data. Wastewater analysis can measure total illicit drug use more
      quickly and regularly than is the current norm for national surveys, and creates
      estimates where such data does not exist.

PMID- 24861848
TI  - Characteristics of acute myeloid leukemia with myelodysplasia-related changes: A
      retrospective analysis in a cohort of Chinese patients.
AB  - We retrospectively analyzed 449 patients with AML under the WHO classification of
      AML 2008 and probed implications of this classification in diagnosis and
      treatment of acute myeloid leukemia with myelodysplasia-related changes (AML-MRC)
      among them. The clinical presentations, biological features, treatments, and
      prognosis of patients diagnosed with AML-MRC were analyzed and compared with
      those of AML not otherwise specified (AML-NOS). In all patients, 115 (25.6%) were
      diagnosed as AML-MRC including 64 males and 51 females with median onset age of
      48 years (range from 17 to 78). Their complete remission (CR) rate was 60.9% and
      relapse rate was 57.1%. The observed median overall survival (OS) and disease
      free survival (DFS) were 10 and 5 months, respectively, which was significantly
      shorter than those of AML-NOS patients (P < 0.05). The prognosis of AML-MRC
      patients with myelodysplastic syndrome (MDS)-related cytogenetics sole was
      similar to those with history of MDS or myelodysplastic/myeloproliferative
      neoplasm (MDS/MPN). Patients with MDS-related cytogenetic abnormalities and/or
      history of MDS or MDS/MPN predisposed significantly shortened CR, OS, and DFS
      than AML-MRC patients with only multilineage dysplasia (MLD) and AML-NOS patients
      (P < 0.05). Multivariate analysis showed that age, cytogenetics, and history of
      MDS or MDS/MPN were independent prognostic factors. Patient diagnosed as AML-MRC
      presented distinctive clinical and biological features. Presence of MLD does not
      change the prognosis.

PMID- 24861849
TI  - From the Table to the Bedside: Can Food-Derived Sulforaphane be used as a Novel
      Agent to Treat Leukemia?
AB  - The extensive use of the same chemotherapeutics over several decades has resulted
      in a growing incidence of chemoresistant cancer cells and secondary malignancies.
      Therefore, there is an increasing need for new drugs to treat high-risk cancer
      patients with a higher selectivity for cancer cells and lower toxicity to normal
      cells. Sulforaphane is released upon hydrolysis of glucoraphanin, a constituent
      of cruciferous vegetables, by myrosinases that are present in the plant or
      intestinal microbes. Despite a large number of studies describing the
      chemopreventive and chemotherapeutic properties of sulforaphane in solid tumors,
      there is little information on the properties of sulforaphane in hematological
      malignancies. In this review, we discuss the anti-carcinogenic properties of
      sulforaphane, the need of higher doses than dietary intake, and the challenges
      related to testing sulforaphane as an adjunctive agent in combination with the
      current standard of care for frontline blood cancer.

PMID- 24861846
TI  - Systematic review of the economic value of diarrheal vaccines.
AB  - Diarrheal disease is a leading cause of child mortality in low-income settings
      and morbidity across a range of settings. A growing number of studies have
      addressed the economic value of new and emerging vaccines to reduce this threat.
      We conducted a systematic review to assess the economic value of diarrheal
      vaccines targeting a range of pathogens in different settings. The majority of
      studies focused on the economic value of rotavirus vaccines in different
      settings, with most of these concluding that vaccination would provide
      significant economic benefits across a range of vaccine prices. There is also
      evidence of the economic benefits of cholera vaccines in specific contexts. For
      other potential diarrheal vaccines data are limited and often hypothetical.
      Across all target pathogens and contexts, the evidence of economic value focuses
      the short-term health and economic gains. Additional information is needed on the
      broader social and long-term economic value of diarrhea vaccines. 

PMID- 24861850
TI  - Porous Ni-Mn oxide nanosheets in situ formed on nickel foam as 3D hierarchical
      monolith de-NO(x) catalysts.
AB  - In this work, we successfully in situ decorated nickel foam with porous Ni-Mn
      oxide nanosheets (3DH-NM/NF) as 3D hierarchical monolith de-NOx catalysts via a
      simple hydrothermal reaction and calcination process. The catalysts were
      carefully examined by X-ray diffraction, scanning electron microscopy,
      transmission electron microscopy, elemental mapping, X-ray photoelectron
      spectroscopy, H2 temperature-programmed reduction and NH3 temperature-programmed
      desorption measurements. The results indicated that the nanosheets are composed
      of a Ni6Mn1O8 spinel and the metal species are uniformly dispersed in bi-metal
      oxides. As a result, the strong synergistic effects between the Mn and Ni species
      have been observed. The active oxygen species, reducible species and acidity are
      enhanced by the in situ formation of the nanosheets on the surface of nickel
      foam. These desirable features of 3DH-NM/NF catalysts bring about the excellent
      de-NOx performance. Moreover, the 3DH-NM/NF catalysts also present good stability
      and H2O resistance. Based on these favorable properties, 3DH-NM/NF could be
      considered as a promising candidate for the monolith de-NOx catalysts. 

PMID- 24861847
TI  - Body size and multiple myeloma mortality: a pooled analysis of 20 prospective
      studies.
AB  - Multiple myeloma (MM) is a rare but highly fatal malignancy. High body weight is
      associated with this cancer, but several questions remain regarding the
      aetiological relevance of timing and location of body weight. To address these
      questions, we conducted a pooled analysis of MM mortality using 1.5 million
      participants (including 1388 MM deaths) from 20 prospective cohorts in the
      National Cancer Institute Cohort Consortium. Proportional hazards regression was
      used to calculate pooled multivariate hazard ratios (HRs) and 95% confidence
      intervals (CIs). Associations with elevated MM mortality were observed for higher
      early-adult body mass index (BMI; HR = 1.22, 95% CI: 1.09-1.35 per 5 kg/m(2) )
      and for higher cohort-entry BMI (HR 1.09, 95% CI: 1.03-1.16 per 5 kg/m(2) ) and
      waist circumference (HR = 1.06, 95% CI: 1.02-1.10 per 5 cm). Women who were the
      heaviest, both in early adulthood (BMI 25+) and at cohort entry (BMI 30+) were at
      greater risk compared to those with BMI 18.5 <= 25 at both time points (HR =
      1.95, 95% CI: 1.33-2.86). Waist-to-hip ratio and height were not associated with
      MM mortality. These observations suggest that overall, and possibly also central,
      obesity influence myeloma mortality, and women have the highest risk of death
      from this cancer if they remain heavy throughout adulthood.

PMID- 24861851
TI  - Andersen-Tawil syndrome: report of 3 novel mutations and high risk of symptomatic
      cardiac involvement.
AB  - INTRODUCTION: Andersen-Tawil syndrome (ATS) is a potassium channelopathy
      affecting cardiac and skeletal muscle. Periodic paralysis is a presenting symptom
      in some patients, whereas, in others, symptomatic arrhythmias or prolongation of
      QT in echocardiographic recordings will lead to diagnosis of ATS. Striking
      intrafamilial variability of expression of KCNJ2 mutations and rarity of the
      syndrome may lead to misdiagnosis. METHODS: We report 15 patients from 8 Polish
      families with ATS, including 3 with novel KCNJ2 mutations. RESULTS: All patients
      had dysmorphic features; periodic paralysis affected males more frequently than
      females (80% vs. 20%), and most attacks were normokalemic. Two patients (with
      T75M and T309I mutations) had aborted sudden cardiac death. An implantable
      cardioverter-defibrillator was utilized in 40% of cases. CONCLUSIONS: KCNJ2
      mutations cause a variable phenotype, with dysmorphic features seen in all
      patients studied, a high penetrance of periodic paralysis in males and
      ventricular arrhythmia with a risk of sudden cardiac death.

PMID- 24861852
TI  - Role of autophagy in embryogenesis.
AB  - Eukaryotes have evolved multiple mechanisms for inactivating macromolecules in
      order to maintain their functionality. Autophagy-the process of self-eating-leads
      to the degradation of cytoplasmic components for the dynamic remodeling of
      subcellular compartments, turnover and recycling of macromolecules, and
      regulation of cellular activity through the control of specific intracellular
      signaling pathways. This fundamental process is also implicated in systemic
      response to starvation and immune challenges, as well as anti-tumorigenesis and
      anti-senescence. Recent studies have also highlighted an important role for
      autophagy in embryonic development. In this review, we discuss the emerging
      evidence for the varied functions of autophagy at different stages of
      development, with an emphasis on the early events of embryogenesis. 

PMID- 24861853
TI  - USL255 extended-release topiramate: dose-proportional pharmacokinetics and
      tolerability in healthy volunteers.
AB  - OBJECTIVE: Evaluate the pharmacokinetics (PK), safety, and tolerability of single
      doses of once-daily USL255, Qudexy XR (topiramate) extended-release capsules,
      over a wide dosing range. METHODS: Two single-dose, phase I studies in healthy
      adults were used to evaluate the PK profile and maximum tolerated dose (MTD) of
      USL255 from 25-1,400 mg. Standard PK parameters assessed included area under the
      plasma concentration-time curve (AUC) and maximum plasma concentration (Cmax ).
      Dose proportionality, linearity, and intersubject and intrasubject variability
      (coefficient of variation [%CV]) of AUC and Cmax were evaluated. Investigator
      reported adverse events (AEs) were obtained throughout the studies. RESULTS:
      After the initial increase in plasma concentration levels immediately following
      administration of USL255 25-1,400 mg, plasma topiramate concentration-time
      profiles were flat up to 24 h after dosing. AUC was dose proportional from 25
      1,400 mg, and Cmax was dose proportional from 50-1,400 mg; both AUC and Cmax were
      linear across the entire dose range. Low intersubject and intrasubject %CV values
      were observed for AUC0-t , AUC0-infinity , and Cmax (intersubject %CV: 20.2,
      19.6, and 22.4%, respectively; intrasubject %CV of dose-normalized mean values:
      10.8, 8.2, and 13.2%, respectively). USL255 was generally safe and well tolerated
      with MTD established at 1,200 mg. SIGNIFICANCE: These results demonstrate that
      USL255 provides consistent plasma topiramate exposure across an extended-dosing
      interval and predictable plasma topiramate concentrations over a wide dosing
      range. Overall, the favorable safety profile and consistency of exposure suggest
      once-daily USL255 can be a useful treatment option for patients with epilepsy.

PMID- 24861854
TI  - The evolutionary appearance of non-cyanogenic hydroxynitrile glucosides in the
      Lotus genus is accompanied by the substrate specialization of paralogous beta
      glucosidases resulting from a crucial amino acid substitution.
AB  - Lotus japonicus, like several other legumes, biosynthesizes the cyanogenic alpha
      hydroxynitrile glucosides lotaustralin and linamarin. Upon tissue disruption
      these compounds are hydrolysed by a specific beta-glucosidase, resulting in the
      release of hydrogen cyanide. Lotus japonicus also produces the non-cyanogenic
      gamma- and beta-hydroxynitrile glucosides rhodiocyanoside A and D using a
      biosynthetic pathway that branches off from lotaustralin biosynthesis. We
      previously established that BGD2 is the only beta-glucosidase responsible for
      cyanogenesis in leaves. Here we show that the paralogous BGD4 has the dominant
      physiological role in rhodiocyanoside degradation. Structural modelling, site
      directed mutagenesis and activity assays establish that a glycine residue (G211)
      in the aglycone binding site of BGD2 is essential for its ability to hydrolyse
      the endogenous cyanogenic glucosides. The corresponding valine (V211) in BGD4
      narrows the active site pocket, resulting in the exclusion of non-flat substrates
      such as lotaustralin and linamarin, but not of the more planar rhodiocyanosides.
      Rhodiocyanosides and the BGD4 gene only occur in L. japonicus and a few closely
      related species associated with the Lotus corniculatus clade within the Lotus
      genus. This suggests the evolutionary scenario that substrate specialization for
      rhodiocyanosides evolved from a promiscuous activity of a progenitor cyanogenic
      beta-glucosidase, resembling BGD2, and required no more than a single amino acid
      substitution. 

PMID- 24861856
TI  - European genetic diversity through space and time.

PMID- 24861855
TI  - Pharmacogenomic diversity in Singaporean populations and Europeans.
AB  - Differences in the frequency of pharmacogenomic variants may influence inter
      population variability in drug efficacy and risk of adverse drug reactions
      (ADRs). We investigated the diversity of ~ 4500 genetic variants in key drug
      biotransformation and -response genes among three South East Asian populations
      compared with individuals of European ancestry. We compared rates of reported
      ADRs in these Asian populations to determine if the allelic differentiation
      corresponded to an excess of the associated ADR. We identified an excess of ADRs
      related to clopidogrel in Singaporean Chinese, consistent with a higher frequency
      of a known risk variant in CYP2C19 in that population. We also observed an excess
      of ADRs related to platinum compounds in Singaporean CHS, despite a very low
      frequency of known ADR risk variants, suggesting the presence of additional
      genetic and non-genetic risk factors. Our results point to substantial diversity
      at specific pharmacogenomic loci that may contribute to inter-population
      variability in drug response phenotypes.

PMID- 24861857
TI  - Ancient DNA: A window to the past of Europe.
AB  - OBJECTIVES: The history of European populations is characterised by numerous
      migrations or demographic events that are likely to have had major impacts on the
      European gene pool patterns. This paper will focus on how ancient DNA (aDNA) data
      contribute to our understanding of past population dynamics in Europe. METHODS:
      Technological challenges of the palaeogenetic approach will be discussed. With
      these limitations in mind, it will be shown that the acquisition of aDNA now
      permits a glimpse of how human genetic diversity has changed, spatially and
      temporally, in Europe, from the Palaeolithic through to the present day. RESULTS:
      Although early modern human DNA sequences come only from rare exceptionally well
      preserved specimens, genetic samples of a reasonable size are becoming available
      for the Mesolithic and the Neolithic periods, permitting a discussion of regional
      variation in the inferred mode of the spread of farming. Palaeogenetic data
      collected for ancient and more recent periods regularly demonstrate genetic
      discontinuity between past and present populations. CONCLUSIONS: The results
      indicate that only large diachronic aDNA datasets from throughout Europe will
      permit researchers to reliably identify all demographic and evolutionary events
      that shaped the modern European gene pool.

PMID- 24861858
TI  - Genetic evidence for prehistoric demographic changes in Europe.
AB  - OBJECTIVES: Two main models have been proposed to explain the origins of the
      patterns of genetic variation in Europe, one emphasizing Paleolithic and the
      other Neolithic immigration from the Southeast. In this paper, I summarize how
      the models developed and how they can help address some open questions. METHODS:
      The rationale of the methods traditionally supporting the Neolithic and the
      Paleolithic models is discussed, and the evidence supporting either of them is
      reviewed. RESULTS: Ancient DNA evidence proves for good that the studies
      traditionally supporting the Paleolithic model had serious methodological flaws.
      This does not imply that the alternative model is right, but rather calls for
      further analyses explicitly testing the two models against the genomic
      information now available. CONCLUSIONS: Questions that need to be addressed
      include whether the two main models differ enough to be discriminated by analyses
      of modern DNA diversity, and to what extent inferences from ancient mitochondrial
      DNA can be trusted in the absence of sufficient datasets of ancient nuclear DNA.
      The time seems ripe for the construction of a more complex (and hence more
      realistic) model, incorporating the possibility of different processes affecting
      different geographic locations at different times.

PMID- 24861859
TI  - Investigating European genetic history through computer simulations.
AB  - BACKGROUND/AIMS: The genetic diversity of Europeans has been shaped by various
      evolutionary forces including their demographic history. Genetic data can thus be
      used to draw inferences on the population history of Europe using appropriate
      statistical methods such as computer simulation, which constitutes a powerful
      tool to study complex models. METHODS: Here, we focus on spatially explicit
      simulation, a method which takes population movements over space and time into
      account. We present its main principles and then describe a series of studies
      using this approach that we consider as particularly significant in the context
      of European prehistory. RESULTS AND CONCLUSION: All simulation studies agree that
      ancient demographic events played a significant role in the establishment of the
      European gene pool; but while earlier works support a major genetic input from
      the Near East during the Neolithic transition, the most recent ones revalue
      positively the contribution of pre-Neolithic hunter-gatherers and suggest a
      possible impact of very ancient demographic events. This result of a substantial
      genetic continuity from pre-Neolithic times to the present challenges some recent
      studies analyzing ancient DNA. We discuss the possible reasons for this
      discrepancy and identify future lines of investigation in order to get a better
      understanding of European evolution.

PMID- 24861860
TI  - The onset of lactase persistence in Europe.
AB  - The genomic region containing the lactase (LCT) gene shows one of the strongest
      signals of positive selection in Europeans, detectable using a range of
      approaches including haplotype length, linked microsatellite variation and
      population-differentiation-based tests. Lactase is the enzyme that carries out
      the digestion of the milk sugar lactose. Its expression decreases at some point
      after the weaning period is over in most mammals and in around 68% of all living
      adult humans. However, in some humans, particularly those from populations with a
      history of dairying, lactase is expressed throughout adulthood. This trait is
      called lactase persistence (LP), and in people of European ancestry, it is
      associated with a single mutation (-13910*T). Evidence from the detection of
      dairy fat residues in potsherds, and allele frequencies in ancient DNA samples
      suggest that LP arose after dairying practices had developed. However, the
      reasons why LP may have been advantageous are still debated, and the respective
      contribution of demography and natural selection remains to be disentangled. This
      paper discusses various studies, from archaeology to population genetics, that
      have shed some light on the subject by investigating the evolution of LP in
      Europe.

PMID- 24861861
TI  - A new HLA map of Europe: Regional genetic variation and its implication for
      peopling history, disease-association studies and tissue transplantation.
AB  - OBJECTIVES: HLA genes are highly polymorphic in human populations as a result of
      diversifying selection related to their immune function. However, HLA geographic
      variation worldwide suggests that demographic factors also shaped their
      evolution. We here analyzed in detail HLA genetic variation in Europe in order to
      identify signatures of migration history and/or natural selection. METHODS:
      Relationships between HLA diversity and geography were analyzed at 7 loci through
      several approaches including linear regression on gene diversity and haplotype
      frequencies. Regional variation was also assessed on HLA multi-locus phenotypes
      through structure analysis. Deviation from neutrality was tested by resampling.
      RESULTS: Geographic distance was a strong predictor of HLA variation at 5 loci
      (A, B, C, DRB1 and DPB1) in Europe, and latitude significantly shaped HLA gene
      diversity and haplotype frequencies. Whereas the main level of genetic diversity
      was found within populations, both HLA gene frequencies and phenotypic profiles
      revealed regional variation, Southeast Europe, Great Britain and Finland being
      the most distinctive. Effects of natural selection were suggested at the DQ loci.
      CONCLUSIONS: HLA regional variation was observed in Europe and can be related to
      population history, locus HLA-A providing by far the strongest signals. This new
      HLA map of Europe represents an invaluable reference for disease-association
      studies and tissue transplantation.

PMID- 24861863
TI  - European genetic diversity and susceptibility to pathogens.
AB  - Infectious diseases, both in their endemic and epidemic forms, have shaped the
      human genome. Ecology has also contributed to geographically constrained
      pressures on human populations. There are now multiple examples of population
      specific genetic variants that modulate susceptibility to infection - several of
      which have been observed solely in Europeans. The pathogen genome also mutates
      and adapts to individuals and common alleles in populations. The current
      understanding has benefited from genome-wide association studies as well as from
      rapid progress in the genetic characterization of Mendelian immunodeficiencies
      that are defined by susceptibility to specific pathogens. It is expected that
      current efforts to characterize rare human genetic variants will contribute to
      the understanding of severe manifestations of common infections in European and
      other human groups.

PMID- 24861862
TI  - Impact of HLA diversity on donor selection in organ and stem cell
      transplantation.
AB  - The human major histocompatibility complex is a multigene system encoding
      polymorphic human leucocyte antigens (HLA) that present peptides derived from
      pathogens to the immune system. The high diversity of HLA alleles and haplotypes
      in the worldwide populations represents a major barrier to organ and allogeneic
      hematopoietic stem cell transplantation, because HLA incompatibilities are
      efficiently recognized by T and B lymphocytes. In organ transplantation, pre
      transplant anti-HLA antibodies need to be taken into account for organ
      allocation. Although HLA-incompatible transplants can be performed thanks to
      immunosuppressive drugs, the de novo production of anti-HLA antibodies still
      represents a major cause of graft failure. The HLAMatchmaker computer algorithm
      determines the immunogenicity of HLA mismatches and allows to define HLA antigens
      that will not induce an antibody response. Because of the much higher stringency
      of HLA compatibility criteria in stem cell transplantation, the best donor is a
      HLA genotypically identical sibling. However, more than 50% of the transplants
      are now performed with hematopoietic stem cells from volunteer donors selected
      from the international registry. The development of European national registries
      covering populations with different HLA haplotype frequencies is essential for
      optimizing donor search algorithms and providing the best chance for European
      patients to find a fully compatible donor.

PMID- 24861864
TI  - Implications of population history of European Romani on genetic susceptibility
      to disease.
AB  - OBJECTIVES: The population history of European Romani is characterized by
      extensive bottleneck and admixture events, but the impact of this unique
      demographic history on the genetic risk for disease remains unresolved. METHODS:
      Genome-wide SNP data on Romani, non-Romani Europeans and Indians were analyzed.
      The excess of homozygous variants in Romani genomes was assessed according to
      their potential functional effect. We also explored the frequencies of risk
      variants associated with five common diseases which are present at an increased
      prevalence in Romani compared to other Europeans. RESULTS: Slightly deleterious
      variants are present at increased frequencies in European Romani, likely a result
      of relaxed purifying selection due to bottlenecks in their population history.
      The frequencies of SNPs associated with common metabolic and cardiovascular
      diseases are also increased compared to their European hosts. CONCLUSIONS: As
      observed in other founder populations, we confirm the impact of bottlenecks on
      the abundance of slightly deleterious variants in Romani groups, probably
      including metabolic and cardiovascular risk variants.

PMID- 24861865
TI  - Genetic variants in apoptosis-related genes associated with colorectal
      hyperplasia.
AB  - Deregulation of apoptosis is a frequent alteration in early benign lesions of the
      colon mucosa and is thought to be a major contributor to tumor progression and
      cancer. Single nucleotide polymorphisms (SNPs) within apoptosis-related genes
      could affect apoptotic responses and their identification might provide a basis
      to assess individual risk for development of early lesions. To investigate a
      possible association between genetic polymorphisms and the occurrence of
      hyperplastic polyps (HP), we developed a custom DNA chip assay for 1,536 SNPs in
      the coding and flanking regions of 826 genes with known functional roles in
      apoptosis or apoptosis-associated (e.g., stress-related) pathways. During a first
      round of screening, genotypes were determined for 272 endoscopy patients
      harboring hyperplastic colorectal polyps and for 512 sex and aged-matched
      controls. A set of 14 candidate SNPs associated with HP (P < 0.01) was then
      evaluated in an independent cohort of patients (n = 38) and controls (n = 38).
      Following meta-analysis of Stages I and II, a false discovery rate approach was
      applied. Among the 14 candidate SNPs, eight showed significant association
      (combined P < 0.01) with the occurrence of HP. The SNPs rs4709583 (PARK2) and
      rs10476823 (HDAC3) were analyzed for potential functional effects on RNA splicing
      and RNA half-life. Despite its location near a splice site, alternative splicing
      was not detected for rs4709583 (PARK3). By contrast, cDNA analysis revealed use
      of a cryptic polyadenylation signal in the 3'UTR of HDAC3 mRNA and a longer mRNA
      half-life in a cell line heterozygous for rs10476823.

PMID- 24861866
TI  - Snail1 induced in breast cancer cells in 3D collagen I gel environment suppresses
      cortactin and impairs effective invadopodia formation.
AB  - Although an in vitro 3D environment cannot completely mimic the in vivo tumor
      site, embedding tumor cells in a 3D extracellular matrix (ECM) allows for the
      study of cancer cell behaviors and the screening of anti-metastatic reagents with
      a more in vivo-like context. Here we explored the behaviors of MDA-MB-231 breast
      cancer cells embedded in 3D collagen I. Diverse tumor environmental conditions
      (including cell density, extracellular acidity, or hypoxia as mimics for a
      continuous tumor growth) reduced JNKs, enhanced TGFbeta1/Smad signaling activity,
      induced Snail1, and reduced cortactin expression. The reduced JNKs activity
      blocked efficient formation of invadopodia labeled with actin, cortactin, or MT1
      MMP. JNKs inactivation activated Smad2 and Smad4, which were required for Snail1
      expression. Snail1 then repressed cortactin expression, causing reduced
      invadopodia formation and prominent localization of MT1-MMP at perinuclear
      regions. MDA-MB-231 cells thus exhibited less efficient collagen I degradation
      and invasion in 3D collagen I upon JNKs inhibition. These observations support a
      signaling network among JNKs, Smads, Snail1, and cortactin to regulate the
      invasion of MDA-MB-231 cells embedded in 3D collagen I, which may be targeted
      during screening of anti-invasion reagents. 

PMID- 24861867
TI  - Myogenesis defect due to Toca-1 knockdown can be suppressed by expression of N
      WASP.
AB  - Skeletal muscle formation is a multistep process involving proliferation,
      differentiation, alignment and fusion of myoblasts to form myotubes which fuse
      with additional myoblast to form myofibers. Toca-1 (Transducer of Cdc42-dependent
      actin assembly), is an adaptor protein which activates N-WASP in conjunction with
      Cdc42 to facilitate membrane invagination, endocytosis and actin cytoskeleton
      remodeling. Expression of Toca-1 in mouse primary myoblasts and C2C12 myoblasts
      was up-regulated on day 1 of differentiation and subsequently down-regulated
      during differentiation. Knocking down Toca-1 expression in C2C12 cells (Toca
      1(KD) cells) resulted in a significant decrease in myotube formation and
      expression of shRNA-resistant Toca-1 in Toca-1(KD) cells rescued the myogenic
      defect, suggesting that the knockdown was specific and Toca-1 is essential for
      myotube formation. Toca-1(KD) cells exhibited elongated spindle-like morphology,
      expressed myogenic markers (MyoD and MyHC) and localized N-Cadherin at cell
      periphery similar to control cells suggesting that Toca-1 is not essential for
      morphological changes or expression of proteins critical for differentiation.
      Toca-1(KD) cells displayed prominent actin fibers suggesting a defect in actin
      cytoskeleton turnover necessary for cell-cell fusion. Toca-1(KD) cells migrated
      faster than control cells and had a reduced number of vinculin patches similar to
      N-WASP(KO) MEF cells. Transfection of N-WASP-expressing plasmid into Toca-1(KD)
      cells restored myotube formation of Toca-1(KD) cells. Thus, our results suggest
      that Toca-1(KD) cells have defects in formation of myotubes probably due to
      reduced activity of actin cytoskeleton regulators such as N-WASP. This is the
      first study to identify and characterize the role of Toca-1 in myogenesis. 

PMID- 24861868
TI  - Swelling kinetics of microgels embedded in a polyacrylamide hydrogel matrix.
AB  - Composite hydrogels--macroscopic hydrogels with embedded microgel particles--are
      expected to respond to external stimuli quickly because microgels swell much
      faster than bulky gels. In this work, the kinetics of the pH-induced swelling of
      a composite hydrogel are studied using turbidity measurements. The embedded
      microgel is a pH- and thermosensitive poly(N-isopropylacrylamide-co-acrylic acid)
      microgel and the hydrogel matrix is polyacrylamide. A rapid pH-induced swelling
      of the embedded microgel particles is observed, confirming that composite
      hydrogels respond faster than ordinary hydrogels. However, compared with the free
      microgels, the swelling of the embedded microgel is much slower. Diffusion of OH(
      ) into the composite hydrogel film is identified as the main reason for the slow
      swelling of the embedded microgel particles, as the time of the pH-induced
      swelling of this film is comparable to that of OH(-) diffusion into the film. The
      composition of the hydrogel matrix does not significantly change the
      characteristic swelling time of the composite hydrogel film. However, the
      swelling pattern of the film changes with composition of the hydrogel matrix.

PMID- 24861869
TI  - Histoplasmosis in a lung transplant recipient from a nonendemic area.

PMID- 24861871
TI  - Using a modification of the Clavien-Dindo system accounting for readmissions and
      multiple interventions: defining quality for pancreaticoduodenectomy.
AB  - BACKGROUND: The Clavien-Dindo system (CD) does not change the grade assigned a
      complication when multiple readmissions or interventions are required to manage a
      complication. We apply a modification of CD accounting for readmissions and
      interventions to pancreaticoduodenectomy (PD). METHODS: PDs done between 1999 and
      2009 were reviewed. CD grade IIIa complications requiring more than one
      intervention and II and IIIa complications requiring significantly prolonged
      lengths of stay including all 90-day readmissions were classified severe-adverse
      postoperative-outcomes (SAPO). CD IIIb, IV, and V complications were also
      classified SAPOs. All other complications were considered minor-adverse
      postoperative-outcomes (MAPO). RESULTS: Four-hundred forty three of 490 PD
      patients (90.4%) had either no complication or a complication of low to moderate
      CD grade (I, II, IIIa). When reclassified by the new metric, 92 patient-outcomes
      (19%) were upgraded from CD II or IIIa to SAPO. One-hundred thirty nine patients
      (28.4%) had a SAPO. Multivariable regression identified age >75 years, pylorus
      preservation and operative blood loss >1,500 ml as predictors of SAPO. Age was
      not associated with poor outcome using the unmodified CD system. CONCLUSIONS:
      Established systems may under-grade the severity of some complications following
      PD. We define a procedure-specific modification of CD accounting for readmissions
      and multiple interventions. Using this modification, advanced age, pylorus
      preservation, and significant blood loss are associated with poor outcome.

PMID- 24861870
TI  - Tumor markers are more useful in patients undergoing surveillance for
      hepatocellular carcinoma with unreliable results by ultrasonography.
AB  - AIM: The objectives of this study was to evaluate the utility of tumor markers in
      hepatocellular carcinoma (HCC) surveillance based on the reliability of
      ultrasonography. METHODS: We analyzed 313 patients with HCC detected through a
      surveillance program using ultrasonography combined with three tumor markers from
      February 2000 to December 2010. The patients were categorized into two groups
      based on the triggering event: the US group (n = 281) in which a tumor was first
      detected using ultrasonography and the TM group (n = 32) in which elevated tumor
      markers led to the diagnosis of a tumor that was undetected using
      ultrasonography. The reliability of ultrasonography was scored on a 4-point scale
      based on three items (coarseness of liver parenchyma, patient obesity and liver
      atrophy). Additionally, patient survival was assessed using the Kaplan-Meier
      method and log-rank test. RESULTS: The median tumor size was 20 mm (interquartile
      range, 15-24). The reliability of ultrasonography was evaluated as good in 208
      (66.5%), satisfactory in 80 (8.0%), poor in 21 (6.7%) and unsatisfactory in four
      (1.2%) patients. The proportion of patients in the TM group increased
      significantly according to the score, from 7.2% to 25.0% (P = 0.01). The survival
      rates of patients at 3 and 5 years were 83.7% and 57.2% in the US group, and
      79.3% and 59.4% in the TM group, respectively (P = 0.98). CONCLUSION: Tumor
      markers may play a diagnostic role in patients with unreliable ultrasonography
      results. The survival of patients diagnosed by elevated tumor markers was not
      significantly different from those diagnosed by ultrasonography.

PMID- 24861872
TI  - Screening for selective inhibitors of xanthine oxidase from Flos Chrysanthemum
      using ultrafiltration LC-MS combined with enzyme channel blocking.
AB  - In this study, a new method based on ultrafiltration liquid chromatography-mass
      spectrometry (UF-LC-MS) combined with enzyme channel blocking (ECB) was developed
      to discover bioactive components from herbal medicines. Xanthine oxidase (XOD), a
      critical enzyme for treating gout, was employed as the target protein for
      screening. By comparing chromatographic profiles of the compounds binding to XOD
      before and after the ECB experiment, the selective ligands could be distinguished
      from the non-selective binders. In this experiment, febuxostat bound to the
      channel entering into the active site of the enzyme and prevented potential
      ligands from binding. Finally, four compounds, namely, luteolin-7-O-glucoside,
      apigenin-7-O-glucoside, luteolin and apigenin were screened and identified as the
      candidate XOD inhibitors based on the ultrafiltration chromatogram of Flos
      Chrysanthemum, a famous traditional Chinese medicine used in many prescriptions
      for gout treatment. To verify the compounds screened further, a microplate method
      was applied to evaluate their enzyme inhibitory activities. The IC50 values of
      the above 4 compounds were 23.61, 38.80, 1.54 and 1.96MUM, respectively. The
      structure-function relationship was also estimated according to the in vitro
      assay. The results were in favor of the hypothesis that the Flos Chrysanthemum
      extract might be used for gout treatment by inhibiting XOD. 

PMID- 24861873
TI  - Development and validation of an LC-MS/MS based method for quantification of 25
      hydroxyvitamin D2 and 25 hydroxyvitamin D3 in human serum and plasma.
AB  - Vitamin D deficiency is increasing in the general population and has become a
      serious public health risk globally. As a reliable clinical indicator of vitamin
      status, 25 hydroxyvitamin D (25(OH)D) has been measured by various methods.
      However, the accuracy of these measurements has been the subject of considerable
      debate. Here, we report the development and validation of a liquid chromatography
      triple quadrupole mass spectrometry based method for the quantification of
      25(OH)D2 and 25(OH)D3 in human serum and plasma samples. Samples were first
      processed by protein precipitation to release the analytes from the vitamin D
      binding protein (DBP), followed by a liquid-liquid extraction procedure. Analysis
      was performed on an LC-MS/MS system which utilized an AB Sciex API 3000 mass
      spectrometer. A six point calibration curve ranging from 2.5 to 100ng/mL was
      established for both 25(OH)D2 and 25(OH)D3. A complete method validation was
      conducted, including intra- and inter-assay accuracy and precision, LLOQ,
      dilution QC, specificity, recovery, matrix effect, and a thorough stability
      profile of stock solutions and QC samples. Matching samples of serum and plasma
      (containing either heparin or EDTA anticoagulant) generated from the same blood
      samples were tested, and no significant differences in 25(OH)D2 and 25(OH)D3
      concentrations were found in these sample matrices. In method comparison, we
      analyzed 10 serum samples obtained from the Vitamin D External Quality Assessment
      Scheme (DEQAS), and the total 25(OH)D concentrations measured by our method were
      very close to the LC-MS/MS Method Mean values provided by DEQAS (average 0.17%
      bias, R(2)=0.99). However, comparison with the DiaSorin Liaison 25(OH)D TOTAL
      Assay demonstrated limited correlation between these two methods (R(2)=0.54). In
      general, concentrations measured by our LC-MS/MS method were roughly 9% higher
      than those measured by the DiaSorin Liaison assay. The correlation with DiaSorin
      Liaison measurement was better for samples in the lower concentration range. In
      summary, we developed and validated an LC-MS/MS based method that can be reliably
      applied in routine quantification of 25(OH)D2 and 25(OH)D3 in human serum and
      plasma samples. This method is not suitable for pediatric determinations due to
      the potential interference of 3-epi 25(OH)D3. 

PMID- 24861875
TI  - Liquid chromatography/tandem mass spectrometry method for simultaneous
      determination of cocaine and its metabolite (-)ecgonine methyl ester in human
      acidified stabilized plasma samples.
AB  - Two simple, sensitive and rapid liquid chromatography/electrospray ionization
      tandem mass spectrometry (LC-ESI-MS/MS) methods (low range and high range) were
      developed and validated for the quantification of cocaine and its metabolite (
      )ecgonine methyl ester (EME) in human acidified stabilized plasma samples. In the
      low range assay, cocaine and the internal standard, cocaine-D3, were extracted
      using a single step liquid-liquid extraction from human acidified stabilized
      plasma. For the high range assay, human acidified stabilized plasma containing
      cocaine, EME, and the internal standards, cocaine-D3 and EME-D3, was mixed with
      acetonitrile, and the protein precipitate was separated by centrifugation. Both
      cocaine and EME extracted from both assays were separated on a HILIC column and
      detected in positive ion mode using multiple reaction monitoring (MRM). Both
      methods were validated and the specificity, linearity, lower limit of
      quantitation (LLOQ), precision, accuracy, recoveries and stability were
      determined. The linear range for the low range assay was 0.01-5ng/mL for cocaine;
      in the high range assay values were 5-1000ng/mL for cocaine and 1-200ng/mL for
      EME. The correlation coefficient (R(2)) values for both assays were 0.993 or
      greater. The precision and accuracy for intra-day and inter-day were better than
      13.0%. The recovery was above 85% and matrix effects were low with the matrix
      factor ranging from 0.817 to 1.10 for both analytes in both assays. The validated
      methods were successfully used to quantify the plasma concentrations of cocaine
      and EME in clinical pharmacokinetic and pharmacodynamic studies. 

PMID- 24861876
TI  - Bactericidal activity of partially oxidized nanodiamonds.
AB  - Nanodiamonds are a class of carbon-based nanoparticles that are rapidly gaining
      attention, particularly for biomedical applications, i.e., as drug carriers, for
      bioimaging, or as implant coatings. Nanodiamonds have generally been considered
      biocompatible with a broad variety of eukaryotic cells. We show that, depending
      on their surface composition, nanodiamonds kill Gram-positive and -negative
      bacteria rapidly and efficiently. We investigated six different types of
      nanodiamonds exhibiting diverse oxygen-containing surface groups that were
      created using standard pretreatment methods for forming nanodiamond dispersions.
      Our experiments suggest that the antibacterial activity of nanodiamond is linked
      to the presence of partially oxidized and negatively charged surfaces,
      specifically those containing acid anhydride groups. Furthermore, proteins were
      found to control the bactericidal properties of nanodiamonds by covering these
      surface groups, which explains the previously reported biocompatibility of
      nanodiamonds. Our findings describe the discovery of an exciting property of
      partially oxidized nanodiamonds as a potent antibacterial agent. 

PMID- 24861874
TI  - Determination of meropenem in bacterial media by LC-MS/MS.
AB  - To support the development of a dynamic in vitro human
      pharmacokinetic/pharmacodynamic simulation model for biofilm-mediated infections
      and study stability of meropenem, an LC-MS/MS method for the determination of
      meropenem in Luria Bertani (LB) media was developed and validated in an API2000
      LC-MS/MS system. A partial validation was also performed in M9 media. Sample
      aliquots of 100MUL (or 25MUL for M9 media) were mixed with the internal standard
      (IS) ceftazidime and filtered. The filtrate was directly injected onto a C8
      column eluted with ammonium formate (10mM, pH 4) and acetonitrile (0.1% formic
      acid) in a gradient mode. ESI(+) and MRM with ion pair m/z 384->68 for meropenem
      and m/z 547->468 for the IS were used for quantification. The calibration curve
      concentration range was 50 to 25,000ng/mL. The recovery was over 98%. In LB
      media, significant signal suppression was observed throughout the time period of
      detection when compared with mobile phase solvents, but the matrix effect was
      compensated well with the IS. In M9 media, much less signal suppression was
      observed. The method is simple, fast, and reliable. Using the method, stability
      of meropenem in LB and M9 media were tested. No significant degradation was
      observed for at least 8h in both LB media (37 degrees C) and M9 media (30 degrees
      C), but more than 15% degradation was observed overnight (~20h). The method was
      transferred to an API5000 LC-MS/MS system using meropenem-d6 as the IS. 

PMID- 24861877
TI  - Vitamin D and subclinical cerebrovascular disease: the Atherosclerosis Risk in
      Communities brain magnetic resonance imaging study.
AB  - IMPORTANCE: Vitamin D deficiency has been associated with hypertension, diabetes
      mellitus, and incident stroke. Little is known about the association between
      vitamin D and subclinical cerebrovascular disease. OBJECTIVE: To examine the
      relationship of 25-hydroxyvitamin D (25[OH]D) levels with cerebrovascular
      abnormalities as assessed on brain magnetic resonance imaging (MRI) among
      participants of the Atherosclerosis Risk in Communities (ARIC) Brain MRI study.
      DESIGN, SETTING, AND PARTICIPANTS: Participants were white and black adults aged
      55 to 72 years with no history of clinical stroke who underwent a cerebral MRI at
      ARIC visit 3 (n = 1622) and a second cerebral MRI approximately 10 years later (n
      = 888). EXPOSURES: The 25(OH)D level was measured by mass spectrometry at visit
      3, with levels adjusted for calendar month and categorized using race-specific
      quartiles. MAIN OUTCOMES AND MEASURES: The cross-sectional and prospective
      associations of 25(OH)D levels with white matter hyperintensities (WMHs) and MRI
      defined infarcts were investigated using multivariable regression models.
      RESULTS: The mean age of the participants was 62 years, 59.6% were women, and
      48.6% were black. Lower 25(OH)D levels were not significantly associated with WMH
      score of severity, prevalent high-grade WMH score (>=3), or prevalent infarcts in
      cross-sectional, multivariable-adjusted models (all P > .05). Similarly, no
      significant prospective associations were found for lower 25(OH)D levels with
      change in WMH volume, incident high WMH score (>=3), or incident infarcts on the
      follow-up MRI, which occurred approximately 10 years later. CONCLUSIONS AND
      RELEVANCE: A single measure of 25(OH)D was not cross-sectionally associated with
      WMH grade or prevalent subclinical infarcts and was not prospectively associated
      with WMH progression or subclinical brain infarcts seen on serial cerebral MRIs
      obtained approximately 10 years apart. These findings do not support optimizing
      vitamin D levels for brain health.

PMID- 24861880
TI  - Editorial commentary on "Analysis of IDH mutation, 1p19q deletion, and PTEN loss
      delineates prognosis in clinical low-grade gliomas".

PMID- 24861878
TI  - JAK2/STAT3 targeted therapy suppresses tumor invasion via disruption of the
      EGFRvIII/JAK2/STAT3 axis and associated focal adhesion in EGFRvIII-expressing
      glioblastoma.
AB  - BACKGROUND: As a commonly mutated form of the epidermal growth factor receptor,
      EGFRvIII strongly promotes glioblastoma (GBM) tumor invasion and progression, but
      the mechanisms underlying this promotion are not fully understood. METHODS:
      Through gene manipulation, we established EGFRvIII-, wild-type EGFR-, and vector
      expressing GBM cells. We used cDNA microarrays, bioinformatics analysis, target
      blocking migration and invasion assays, Western blotting, and an orthotopic U87MG
      GBM model to examine the phenotypic shifts and treatment effects of EGFRvIII
      expression in vitro and in vivo. Confocal imaging, co-immunoprecipitation, and
      siRNA assays detected the focal adhesion-associated complex and their
      relationships to the EGFRvIII/JAK2/STAT3 axis in GBM cells. RESULTS: The
      activation of JAK2/STAT3 signaling is vital for promoting migration and invasion
      in EGFRvIII-GBM cells. AG490 or WP1066, the JAK2/STAT3 inhibitors, specifically
      destroyed EGFRvIII/JAK2/STAT3-related focal adhesions and depleted the activation
      of EGFR/Akt/FAK and JAK2/STAT3 signaling, thereby abolishing the ability of
      EGFRvIII-expressing GBM cells to migrate and invade. Furthermore, the RNAi
      silencing of JAK2 in EGFRvIII-expressing GBM cells significantly attenuated their
      ability to migrate and invade; however, as a result of a potential EGFRvIII-JAK2
      STAT3 activation loop, neither EGFR nor STAT3 knockdown yielded the same effects.
      Moreover, AG490 or JAK2 gene knockdown greatly suppressed tumor invasion and
      progression in the U87MG-EGFRvIII orthotopic models. CONCLUSION: Taken together,
      our data demonstrate that JAK2/STAT3 signaling is essential for EGFRvIII-driven
      migration and invasion by promoting focal adhesion and stabilizing the
      EGFRvIII/JAK2/STAT3 axis. Targeting JAK2/STAT3 therapy, such as AG490, may have
      potential clinical implications for the tailored treatment of GBM patients
      bearing EGFRvIII-positive tumors.

PMID- 24861881
TI  - Temporal trends in femoral diaphyseal torsional asymmetry among the Arikara
      associated with postural behavior.
AB  - Average femoral torsion has been reported to differ among populations, and
      several studies have observed a relatively high prevalence of femoral anteversion
      asymmetry in Native Americans, especially females. This study investigates sexual
      dimorphism and temporal trends in femoral torsional asymmetry among the Arikara
      from the seventeenth to the early nineteenth century. To establish if there are
      population differences, femoral torsion was first measured using a direct method
      on a diverse comparative sample of Native Americans from the Southwest, Midwest,
      and Great Plains as well as American Whites and Blacks. To examine temporal
      trends among the Arikara, femoral torsion was examined using the orientation of
      the maximum bending rigidity at subtrochanteric in 154 females and 164 males from
      three temporal variants of the Arikara Coalescent tradition. There is significant
      sexual dimorphism in femoral torsional directional and absolute asymmetry among
      most Native American samples, but not among American Whites and Blacks. Among the
      Arikara there is significant sexual dimorphism in femoral torsional asymmetry in
      all three temporal variants, and asymmetry in femoral torsional asymmetry
      increased significantly from the protohistoric to the early historic period among
      females. The increased femoral torsional asymmetry is likely associated with a
      common side-sitting posture observed in historic photographs of Great Plains
      females. Historic Arikara females may have habitually sat in this compulsory
      position for extended periods while conducting domestic chores. The dramatic
      change from the protohistoric to historic period suggests a cultural change in
      sitting posture among females that was widespread across the Northern Plains.

PMID- 24861879
TI  - MiR-124 governs glioma growth and angiogenesis and enhances chemosensitivity by
      targeting R-Ras and N-Ras.
AB  - BACKGROUND: Glioma is one of the most aggressive and lethal human brain tumors.
      Accumulating evidence shows that microRNAs play important roles in cancers,
      including glioma. Previous studies reported that miR-124 levels were
      downregulated in glioma specimens. Here, we further investigate the potential
      role of miR-124 in glioma. METHODS: The expression levels of miR-124 were
      detected in glioma specimens by quantitative reverse transcriptase PCR. The
      direct targets of miR-124 were identified by bioinformatics analysis and were
      further validated by immunoblotting and luciferase reporter assay. The effects of
      miR-124 on glioma cell proliferation and chemosensitivity to temozolomide were
      analyzed by Cell-Counting Kit 8 assay. Apoptosis was evaluated by fluorescence
      activated cell sorting analysis. A xenograft model was used to study the effect
      of miR-124 on tumor growth and angiogenesis. RESULTS: Expression levels of miR
      124 were greatly downregulated in glioma specimens. related Ras viral oncogene
      homolog (R-Ras) and neuroblastoma Ras viral oncogene homolog (N-Ras) were
      identified as direct targets of miR-124. MiR-124 inhibited glioma cell growth,
      invasion, angiogenesis, and tumor growth and increased chemosensitivity to
      temozolomide treatment by negatively regulating the Ras family and its downstream
      signaling pathways: phosphatidylinositol-3 kinase/Akt and Raf/extracellular
      signal-regulated kinase 1/2. Furthermore, overexpression of R-Ras rescued the
      inhibitory effects of miR-124. Meanwhile, overexpression of R-Ras and N-Ras
      restored miR-124-inhibited vascular endothelial growth factor (VEGF)
      transcription activation. In clinical glioma specimens, protein levels of R-Ras
      and N-Ras were upregulated and inversely correlated with miR-124 expression
      levels. CONCLUSIONS: Taken together, these results revealed that miR-124 levels
      in tumor tissues are associated with glioma occurrence, angiogenesis, and
      chemoresistance and that miR-124 may be used as a new diagnostic marker and
      therapeutic target for glioma in the future.

PMID- 24861883
TI  - Osteoporosis: a lifecourse approach.
AB  - It is becoming increasingly apparent that the risk of developing osteoporosis is
      accrued throughout the entire lifecourse, even from as early as conception. Thus
      early growth is associated with bone mass at peak and in older age, and risk of
      hip fracture. Novel findings from mother-offspring cohorts have yielded greater
      understanding of relationships between patterns of intrauterine and postnatal
      growth in the context of later bone development. Study of biological samples from
      these populations has helped characterize potential mechanistic underpinnings,
      such as epigenetic processes. Global policy has recognized the importance of
      early growth and nutrition to the risk of developing adult chronic
      noncommunicable diseases such as osteoporosis; testing of pregnancy interventions
      aimed at optimizing offspring bone health is now underway. It is hoped that
      through such programs, novel public health strategies may be established with the
      ultimate goal of reducing the burden of osteoporotic fracture in older age.

PMID- 24861882
TI  - Salvage of grafts with vascular thrombosis during live donor renal
      allotransplantation: a critical analysis of successful outcome.
AB  - OBJECTIVES: To report a high-volume institution experience with salvage
      techniques for vascular accidents during live donor renal allotransplantation.
      METHODS: Between March 1976 and January 2011, 2208 recipients underwent live
      donor renal allotransplantation. A retrospective review of recipients with
      vascular accidents - renal artery thrombosis and renal vein thrombosis - was
      carried out. Salvage procedures were recorded and their outcomes were assessed.
      RESULTS: A total of 23 (1%) vascular accidents occurred, including renal artery
      thrombosis and renal vein thrombosis in 19 (0.8%) and four (0.18%) recipients,
      respectively. All renal artery thrombosis patients were treated by open
      revascularization and the graft was salvaged in 12 patients (63%). Two renal vein
      thrombosis events were resolved by percutaneous catheter-directed thrombolytic
      therapy. Of the other two allografts, one was salvaged by thrombectomy and
      revascularization, and the other was lost. On univariable analysis, older
      recipients (P = 0.003), pretransplant hypertension (P =  0.001), more human
      leukocyte antigen mismatches (>=3; P = 0.036), shorter ischemia time (<=45 min; P
      = 0.004) and longer time to diagnosis (>3.5 days; P = 0.013) were significantly
      associated with non-salvage of the graft after vascular accidents. Nevertheless,
      none of these variables were significant on the multivariable analysis. Over a
      median follow up of 35 months, the median (range) serum creatinine was 2 mg/dL
      (range 0.8-8.8 mg/dL), and 11 (79%) recipients were living with functioning
      grafts. CONCLUSIONS: Despite the devastating complications, vascular accidents
      are salvageable and revascularization is crucial for graft salvage. Angiographic
      percutaneous techniques are viable alternatives for renal vein thrombosis.

PMID- 24861884
TI  - Exophytic glioma of the medulla: presentation, management and outcome.
AB  - OBJECTIVE: Exophytic gliomas of the medulla are rare childhood tumors that mostly
      are pilocytic astrocytomas. Here we report our experience in 11 -children with
      this rare tumor. METHODS: A retrospective study was performed using the records
      of children with exophytic gliomas of the medulla at Children's Hospital Medical
      Center in Tehran, Iran, from 2002 through 2013. The general, clinical, and
      radiological data and follow-up of all patients were reviewed. RESULTS: The
      patients mostly were male aged from 11 months to 7 years. Swallowing problems,
      failure to thrive and nausea and vomiting were the most common symptoms. The time
      span between the onset of symptoms and the diagnosis was 2-24 months. Gross total
      resection of tumor was possible in 8 patients. Most tumors were pilocytic
      astrocytomas. Patients were followed for 2 months to 11 years (mean = 3.6 years).
      There was no intraoperative mortality. Recurrence occurred in 1 child with
      fibrillary astrocytoma. CONCLUSION: Gross total resection of symptomatic dorsal
      exophytic medullary glioma is recommended. Most tumors are pilocytic
      astrocytomas. The attachment of these tumors to important brainstem structures
      usually inhibits total resection. Electrophysiological monitoring of sensorimotor
      pathways and cranial nerves can be helpful to preserve surrounding neural tissue
      during tumor resection and to minimize complications. Regular follow-up of
      patients with clinical examination and brain MRI is mandatory. Repeated surgery,
      radiation therapy and chemotherapy are suggested in cases with tumor recurrence
      or progression.

PMID- 24861885
TI  - HIV co-infection accelerates decay of humoral responses in spontaneous resolvers
      of HCV infection.
AB  - Acute hepatitis C virus (HCV) infection is primarily followed by chronic
      infection, while spontaneous recovery of HCV infection (SR-HCV) occurs in a
      minority of those infected. Identification of SR-HCV clinically depends on two
      combined indicators, persistently undetectable peripheral HCV RNA and positivity
      for anti-HCV. However, the characteristics of dynamic variation in anti-HCV
      antibodies in SR-HCV, especially in those patients co-infected with HIV, are
      still undefined. In this study, a cohort of patients infected with HCV through
      commercial blood collection practices was studied. We found that the annual
      decreasing rate of anti-HCV presented a gradually accelerated process in HCV
      resolvers. However, the variation in the decline of anti-HCV presented a slowly
      accelerated process within the early decrease stage and a gradually decelerated
      process within the latter decrease stage. In addition, we deduced that it
      expended approximately 16 years from natural HCV recovery to undetectable
      peripheral anti-HCV in HCV resolvers co-infected with HIV, while this time was
      estimated to be 20 years in SR-HCV without HIV co-infection. Our data indicated
      that the decay of anti-HCV was accelerated by HIV-related impairment of immune
      function. The prevalence of HCV infection may be severely underestimated in this
      large-scale retrospective epidemiologic investigation in an HIV-infected
      population.

PMID- 24861886
TI  - Delphinol(r) standardized maqui berry extract reduces postprandial blood glucose
      increase in individuals with impaired glucose regulation by novel mechanism of
      sodium glucose cotransporter inhibition.
AB  - AIM: The impetus of our study was to investigate the effects of a nutritional
      supplement Delphinol(r), an extract of maqui berries (Aristotelia chilensis)
      standardised to >=25% delphinidins and >=35% total anthocyanins, on postprandial
      blood glucose and insulin levels and identify the physiologic mechanism involved.
      METHODS: Postprandial blood glucose and insulin were investigated in double
      blind, placebo-controlled, cross-over fashion in ten volunteers with moderate
      glucose intolerance. Longer term effects on blood sugar levels were investigated
      in streptozotocin-diabetic rats over a four months period. Effects of maqui berry
      delphinidins on sodium-glucose symport were examined in rodent jejenum of the
      small intestine. RESULTS: Delphinol(r) intake prior to rice consumption
      statistical significantly lowered post prandial blood glucose and insulin as
      compared to placebo. We identified an inhibition of Na+-dependant glucose
      transport by delphinidin, the principal polyphenol to which Delphinol(r) is
      standardised. In a diabetic rat model the daily oral application of Delphinol(r)
      over a period of four months significantly lowered fasting blood glucose levels
      and reached values indistinguishable from healthy non-diabetic rats. CONCLUSION:
      Our results suggest a potential use of Delphinol(r) for naturally controlling
      post-prandial blood glucose owed to inhibition of sodium glucose co-transporter
      in small intestine.

PMID- 24861887
TI  - Effects of thienorphine on synaptic structure and synaptophysin expression in the
      rat nucleus accumbens.
AB  - The partial opioid agonist thienorphine is currently in Phase II clinical trials
      in China as a candidate drug for the treatment of opioid dependence. However, its
      effect on synaptic plasticity in the NAc (nucleus accumbens) remains unclear. In
      the present study, we measured structural parameters of the synaptic interface to
      investigate the effect of thienorphine, morphine or a combination of both on
      synaptic morphology in the NAc of rats. Expression of synaptophysin was also
      examined. Ultrastructural observation showed that synaptic alterations were less
      pronounced after chronic thienorphine administration than after chronic morphine
      administration. Animals that received thienorphine had thinner postsynaptic
      densities and shorter active zones in the NAc compared with those in the saline
      group, but the active zone was larger, and the cleft narrower, than those in the
      morphine group. Furthermore, synaptophysin expression in the NAc was
      significantly greater after chronic administration of thienorphine, morphine, or
      both, than after saline. These results identified interesting differences between
      thienorphine and morphine in their effects on synaptic structure and
      synaptophysin expression in the rat NAc. Further study is deserved to investigate
      thienorphine as a new treatment for opioid dependence. 

PMID- 24861888
TI  - A comparison of methods for focusing the field of a HIFU array transducer through
      human ribs.
AB  - A forward model, which predicts the scattering by human ribs of a multi-element
      high-intensity focused ultrasound transducer, was used to investigate the
      efficacy of a range of focusing approaches described in the literature. This
      forward model is based on the boundary element method and was described by Gelat
      et al (2011 Phys. Med. Biol. 56 5553-81; 2012 Phys. Med. Biol. 57 8471-97). The
      model has since been improved and features a complex surface impedance condition
      at the surface of the ribs. The inverse problem of focusing through the ribs was
      implemented on six transducer array-rib topologies and five methods of focusing
      were investigated, including spherical focusing, binarized apodization based on
      geometric ray tracing, phase conjugation and the decomposition of the time
      reversal operator method. The excitation frequency was 1 MHz and the array was of
      spherical-section type. Both human and idealized rib topologies were considered.
      The merit of each method of focusing was examined. It was concluded that the
      constrained optimization approach offers greater potential than the other
      focusing methods in terms of maximizing the ratio of acoustic pressure magnitudes
      at the focus to those on the surface of the ribs whilst taking full advantage of
      the dynamic range of the phased array. 

PMID- 24861889
TI  - Optimization of a validated stability-indicating RP-LC method for the
      determination of fulvestrant from polymeric based nanoparticle systems, drugs and
      biological samples.
AB  - Fulvestrant is used for the treatment of hormone receptor-positive metastatic
      breast cancer in postmenopausal women with disease progression following anti
      estrogen therapy. Several reversed-phase columns with variable silica materials,
      diameters, lengths, etc., were tested for the optimization study. A good
      chromatographic separation was achieved using a Waters X-Terra RP(18) column (250
      * 4.6 mm i.d. * 5 um) and a mobile phase, consisting of a mixture of acetonitrile
      water (65:35; v/v) containing phosphoric acid (0.1%). The separation was carried
      out 40  degrees C with detection at 215 nm.The calibration curves were linear
      over the concentration range between 1.0-300 and 1.0-200 ug/mL for standard
      solutions and biological media, respectively. The proposed method is accurate and
      reproducible. Forced degradation studies were also realized. This fully validated
      method allows the direct determination of fulvestrant in dosage form and
      biological samples. The average recovery of the added fulvestrant amount in the
      samples was between 98.22 and 104.03%. The proposed method was also applied for
      the determination of fulvestrant from the polymeric-based nanoparticle systems.
      No interference from using polymers and other excipients was observed in in vitro
      drug release studies. Therefore an incorporation efficiency of fulvestrant-loaded
      nanoparticle could be determined accurately and specifically.

PMID- 24861890
TI  - PtSerpin from the swimming crab Portunus trituberculatus, a putative regulator of
      prophenoloxidase activation with antibacterial activity.
AB  - Serpin or serine protease inhibitor is the largest family of protease inhibitors
      involved in many innate immune pathways, particularly the prophenoloxidase
      (proPO) activating system in arthropod. Here, we report the molecular and
      functional characterization of PtSerpin identified from the swimming crab
      Portunus trituberculatus. The genomic sequence encoding mature peptide of
      PtSerpin gene contained two exons of 84 and 1098 bp separated by one intron of
      111 bp. The recombinant PtSerpin (rPtSerpin) with a predicted size of 44 kDa was
      expressed in Escherichia coli system, purified and assayed for its activities.
      The rPtSerpin exhibited inhibitory activity against trypsin in a dose-dependent
      manner, but did not affect chymotrypsin, which could define a role for PtSerpin
      as a trypsin inhibitor. The rPtSerpin could inhibit the growth of Gram-negative
      bacterium Vibrio alginolyticus, but not the tested Gram-positive bacterium and
      fungus. Further phenoloxidase (PO) assay showed PO activity was dramatically
      increased in hemocyte lysate supernatant of P. trituberculatus upon bacterial
      challenge. The rPtSerpin could depress the crab proPO system activation in vitro,
      and it could lead to 100% inhibition of PO activity under the concentration of
      8.62 MUM. Moreover, the rPtSerpin was able to inhibit the PO activity induced by
      rPtcSP and rPtSPH1. These results together indicate that PtSerpin is a potential
      trypsin inhibitor and may participate in crab innate immunity by the inhibition
      of bacterial growth and the regulation of proPO system.

PMID- 24861891
TI  - Molecular cloning, characterization and gene expression of murrel CXC chemokine
      receptor 3a against sodium nitrite acute toxicity and microbial pathogens.
AB  - CXCR3 is a CXC chemokine receptor 3 which binds to CXC ligand 4 (CXCL4), 9, 10
      and 11. CXC chemokine receptor 3a (CXCR3a) is one of the splice variants of
      CXCR3. It plays crucial role in defense and other physiological processes. In
      this study, we report the molecular cloning, characterization and gene expression
      of CXCR3a from striped murrel Channa striatus (Cs). The full length CsCXCR3a cDNA
      sequence was obtained from the constructed cDNA library of striped murrel by
      cloning and sequencing using an internal sequencing primer. The full length
      sequence is 1425 nucleotides in length including an open reading frame of 1086
      nucleotides which is encoded with a polypeptide of 361 amino acids (mol. wt. 40
      kDa). CsCXCR3a domain analysis showed that the protein contains a G protein
      coupled receptor between 55 and 305 along with its family signature at 129-145.
      The transmembrane prediction analysis showed that CsCXCR3a protein contains 7
      transmembrane helical regions at 34-65, 80-106, 113-146, 154-181, 208-242, 249
      278 and 284-308. The 'DRY' motif from CsCXCR3a protein sequence at (140)Asp
      (141)Arg-(142)Tyr which is responsible for G-protein binding is also highly
      conserved with CXCR3 from other species. Phylogenetic tree showed that the CXC
      chemokine receptors 3, 4, 5 and 6, each formed a separate clade, but 1 and 2 were
      clustered together, which may be due to the high similarity between these
      receptors. The predicted 3D structure revealed cysteine residues, which are
      responsible for 'CXC' motif at 116 and 198. The CsCXR3a transcript was found to
      be high in kidney, further its expression was up-regulated by sodium nitrite
      acute toxicity exposure, fungal, bacterial and poly I:C challenges. Overall,
      these results supported the active involvement of CsCXCR3a in inflammatory
      process of striped murrel during infection. However, further study is necessary
      to explore the striped murrel chemokine signaling pathways and their roles in
      defense system.

PMID- 24861892
TI  - Change in levels of physical activity after diagnosis of type 2 diabetes: an
      observational analysis from the NAVIGATOR study.
AB  - Increased physical activity is known to be beneficial in people with type 2
      diabetes mellitus (T2DM), but it is not known whether individuals change their
      activity levels after T2DM diagnosis. The present Nateglinide and Valsartan in
      Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial, conducted in
      participants with impaired glucose tolerance at high cardiovascular risk,
      assessed ambulatory activity annually using research-grade pedometers. Oral
      glucose tolerance tests were performed annually and repeated to confirm T2DM
      diagnosis. This observational analysis used general linear models to compare step
      counts before and after T2DM diagnosis in the 2816 participants with the
      requisite data. Participants were relatively inactive at baseline, taking a
      median (interquartile range) of 5488 (3258-8361) steps/day, which decreased after
      T2DM diagnosis by a mean (s.e.) of 258 (64) steps/day (p < 0.0001); however,
      after adjusting for background trend for activity, step count after T2DM
      diagnosis was unchanged [mean (s.e.) of 103 (87) fewer steps/day; p = 0.23].
      Awareness of T2DM diagnosis had no impact on the trajectory of activity
      established before the diagnosis.

PMID- 24861893
TI  - New epidemiology of Staphylococcus aureus infections in the Middle East.
AB  - Staphylococcus aureus is a bacterial pathogen that is distributed worldwide and
      represents an increasing problem, both in hospitals and in the community. Global
      transmission of methicillin-resistant S. aureus (MRSA) has been the subject of
      many studies. Determining the incidence of colonization with community-acquired
      MRSA in hospitalized patients and outpatients has been the aim of several studies
      conducted in the Middle East (western Asia). The local epidemiology within
      countries in this region is changing, owing to the introduction of new strains
      with the intercontinental exchange of several clones. Sequence type 80-MRSA-IV is
      one common clone detected in different countries within the region showing
      country-based differences, and hence more likely to form clonal lineages. MRSA is
      endemic in this region, and the burden and the difficulty in detecting imported
      strains are increasing. This is also increasing the risk of domestic and global
      transmission. To counter the threat associated with the high incidence of MRSA
      carriage and infections, systematic surveillance of both hospital and community
      isolates is required, along with appropriate measures designed to limit their
      spread. Additionally, antibiotic stewardship is needed to contain the further
      development of the observed resistance and to help in preserving antibiotics as
      precious therapeutic resources. It is critical for countries in this region to
      establish both national and international initiatives to develop better
      measurements designed to limit and control the spread of infections. Finally,
      more sequence-based studies are needed to better understand the pathogenicity and
      epidemiology of these important pathogens.

PMID- 24861894
TI  - Correlation between histological signs of placental underperfusion and perinatal
      morbidity in late-onset small-for-gestational-age fetuses.
AB  - OBJECTIVE: To investigate whether signs of placental underperfusion (PUP),
      defined as any maternal and/or fetal vascular pathology, confer an increased risk
      of neonatal morbidity in late-onset small-for-gestational-age (SGA) fetuses with
      normal umbilical artery (UA) Doppler indices. METHODS: A cohort of 126 SGA
      singleton fetuses with normal UA Doppler indices that were delivered after 34
      weeks' gestation was studied. For each case, the placenta was evaluated
      histologically for signs of PUP using a hierarchical and standardized
      classification system. Neonatal morbidity was assessed according to the score
      calculated from the morbidity assessment index for newborns (MAIN), a validated
      outcome scale. The independent association between PUP and neonatal morbidity was
      evaluated using multivariable median regression analysis. RESULTS: In 84 (66.7%)
      placentae, 97 placental histological findings that qualified as signs of PUP were
      observed. These PUP cases had a significantly higher incidence of emergency
      Cesarean section for non-reassuring fetal status (44.1% vs 21.4%, respectively; P
      = 0.013) and neonatal metabolic acidosis at birth (33.3% vs 14.3%, respectively;
      P = 0.023), than did those without PUP. The median MAIN score differed
      significantly between those with PUP and those without (89 vs 0, respectively; P
      = 0.025). This difference remained significant after adjustment for potential
      confounders. The proportion of cases with scores indicative of mild to severe
      morbidity was also significantly higher in the PUP group (31% vs 14.3%,
      respectively; P = 0.043). CONCLUSION: In late-onset SGA fetuses with normal UA
      Doppler indices, signs of PUP imply a higher neonatal morbidity. These findings
      allow the phenotypic profiling of fetal growth restriction among the general
      population of late-onset SGA.

PMID- 24861895
TI  - CCM8: the eighth international symposium on inorganic carbon uptake by aquatic
      photosynthetic organisms.
AB  - The articles in this special issue of Photosynthesis Research arose from the
      presentations given at the Eighth International Symposium on Inorganic Carbon
      Uptake by Aquatic Photosynthetic Organisms held from May 27 to June 1, 2013 in
      New Orleans, Louisiana USA. The meeting covered all the aspects of CO2
      concentrating mechanisms (CCMs) present in photosynthetic bacteria, microalgae
      and macrophytes, and spanned disciplines from the molecular biology of CCMs to
      the importance of CCMs in aquatic ecosystems. The publications in this special
      issue represent our current understanding of CCMs and highlight recent advances
      in the field. The influences of CCMs on algal biofuel production as well as
      recent efforts to use the CCM to improve crop plants are also explored. 

PMID- 24861896
TI  - Light-dependent conformational change of neoxanthin in a siphonous green alga,
      Codium intricatum, revealed by Raman spectroscopy.
AB  - Siphonous green algae, a type of deep-sea green algae, appear olive drab and
      utilize blue-green light for photosynthesis. A siphonous green alga, Codium (C.)
      intricatum, was isolated from Okinawa prefecture in Japan, and a clonal algal
      culture in filamentous form was established. The major light-harvesting antenna
      was analogous to the trimeric LHCII found in higher plants, but the C. intricatum
      complex contained an unusual carbonyl carotenoid siphonaxanthin. Culture
      conditions were optimized to achieve high siphonaxanthin content in intact
      lyophilized filamentous bodies. Interestingly, the carotenoid composition was
      different when cultured under high irradiance: all-trans neoxanthin was
      accumulated in addition to the normal 9'-cis form in whole cell extract.
      Resonance Raman spectra of intact filamentous bodies, cultured under high- and
      low-light conditions, confirmed the accumulation of all-trans neoxanthin under
      high irradiance conditions. A plausible function of the presence of all-trans
      neoxanthin will be discussed in relation to the regulation against high light
      stress. 

PMID- 24861897
TI  - Stories and photographs of William A. Arnold (1904-2001), a pioneer of
      photosynthesis and a wonderful friend.
AB  - William A. Arnold discovered many phenomena in photosynthesis. In 1932, together
      with Robert Emerson, he provided the first experimental data that led to the
      concept of a large antenna and a few reaction centers (photosynthetic unit); in
      1935, he obtained the minimum quantum requirement of 8-10 for the evolution of
      one O2 molecule; in 1951, together with Bernard L. Strehler, he discovered
      delayed fluorescence (also known as delayed light emission) in photosynthetic
      systems; and in 1956, together with Helen Sherwood, he discovered
      thermoluminescence in plants. He is also known for providing a solid-state
      picture of photosynthesis. Much has been written about him and his research,
      including many articles in a special issue of Photosynthesis Research (Govindjee
      et al. (eds.) 1996); and a biography of Arnold, by Govindjee and Srivastava
      (William Archibald Arnold (1904-2001), 2014), in the Biographical Memoirs of the
      US National Academy of Sciences, (Washington, DC). Our article here offers a
      glimpse into the everyday life, through stories and photographs, of this
      remarkable scientist. 

PMID- 24861898
TI  - A review of the innate immune defence of the human foetus and newborn, with the
      emphasis on antimicrobial peptides.
AB  - At birth, the foetus makes the transition from the uterus to a world full of
      microbes. The newborn baby needs protection against potential invading pathogens
      and needs to establish a normal microbiota. CONCLUSION: Antimicrobial peptides
      and proteins are key effector molecules of innate immunity and are also important
      immunomodulators. Their presence in the cells and tissues of the uterus, foetus
      and the neonate indicates an important role in immunity during pregnancy and in
      early life.

PMID- 24861900
TI  - Rational design of multifunctional hetero-hexameric proteins for hydrogel
      formation and controlled delivery of bioactive molecules.
AB  - A hetero-hexameric protein system is developed in this study, which not only
      functions as cross-linkers for hydrogel formation but also offers docking sites
      for controlled delivery of bioactive molecules. First, a hexameric protein with
      two, four, and six tax-interacting protein-1 (TIP-1), respectively (named as 2T,
      4T, and 6T), is designed and obtained. As the hexapeptide ligand (WRESAI) can
      specifically bind to TIP-1 with high affinity, the hexameric proteins of 2T, 4T,
      and 6T can be used to crosslink the self-assembling nanofibers of Nap
      GFFYGGGWRESAI, leading to formation of injectable biohybrid hydrogels with
      tunable mechanical properties. Furthermore, a hetero-hexameric protein containing
      four TIP-1 and two C-terminal moiety of the pneumococcal cell-wall amidase LytA
      (C-LytA) proteins is designed and engineered (named as 4T2C). The 4T2C proteins
      can not only serve as cross-linkers for hydrogel formation but also provide
      docking sites for loading and controlled release of model drug Rhoda-GGK'. This
      study opens up new opportunities for further development of multifunctional
      hetero- recombinant protein-based hydrogels for biological applications. 

PMID- 24861901
TI  - Design and synthesis of perpendicularly connected metal porphyrin-imide dyads for
      two-terminal wired single molecular diodes.
AB  - Four different porphyrin-imide dyads bearing different central metals (zinc or
      rhodium) and different substituents on the porphyrin macrocycles (tert-butyl or
      methoxy) were synthesized for single molecular diode measurements. The molecules
      were designed to separate the donor component (porphyrin) from the acceptor
      component (imide) by bonding in a perpendicular arrangement, thus enhancing the
      rectification properties. UV/Vis absorption spectra and density functional theory
      calculations showed that the design was successful and that the molecular
      orbitals of the dyads were the summation of the two components, with minimal
      interaction between them. The effect of the central metal was found to be
      significant, with the lowest energy absorption for the zinc dyads being
      attributed to the mixed state of charge transfer from porphyrin to imide and the
      Q band, whereas that of the rhodium dyads indicated insignificant charge-transfer
      character. 

PMID- 24861899
TI  - Binding profiles and cytokine-inducing effects of fish rhamnose-binding lectins
      on Burkitt's lymphoma Raji cells.
AB  - Rhamnose-binding lectin (RBL) is one of the animal lectin categories which take
      part in the innate immune responses of fish. Osmerus lanceolatus lectin (OLL)
      from shishamo smelt eggs is an RBL composed of two tandem-repeated domains, both
      of which are considered to be a carbohydrate-recognition domain. SAL, catfish
      (Silurus asotus) egg RBL composed of three domains, binds to Burkitt's lymphoma
      Raji cells through globotriaosylceramide (Gb3) carbohydrate chain and to reduce
      cell size and growth by altering membrane composition without causing cell death.
      In this experiment, we tried to compare the binding effects of these two RBLs on
      Raji cells. Flow cytometric and fluorescence microscopic analyses revealed that
      OLL also directly bound to and shrunk Raji cells with ten times less reactivity
      than SAL but reduced cell growth with decreasing cell viability. Anti-Gb3
      antibody completely blocked the binding of SAL to Raji cells but not that of OLL.
      In addition, the direct bindings of OLL and SAL to Raji cells were comparably
      inhibited by melibiose, but lactose was more effective inhibitor for the binding
      of OLL than that of SAL. These results suggest that OLL has slightly different
      cell-binding property compared with SAL and binds not only to Gb3 but also to the
      other carbohydrate receptor-bearing beta-galactoside chains. The quantitative RT
      PCR analysis revealed that SAL induced the expression of TNF-alpha but not of IFN
      gamma, IL-1beta, and IL-10. Thus, SAL-induced cytostatic effect on Raji cells
      might be partially caused by TNF-alpha-mediated signaling pathway.

PMID- 24861902
TI  - The effect of caffeine on choroidal thickness in young healthy subjects.
AB  - BACKGROUND: To investigate the effect of oral caffeine intake on choroidal
      thickness using optical coherence tomography (OCT). METHODS: Eighteen otherwise
      healthy caffeine users and 18 controls were enrolled. All participants underwent
      OCT scanning with high-speed and resolution spectral-domain OCT device (3D OCT
      2000, Topcon, Japan) at baseline, and 1 and 3 h following 200-mg oral caffeine
      intake in the study and after oral placebo in the control group. The measurements
      were taken in the morning (10-12 am) to avoid diurnal fluctuation. RESULTS: The
      median choroidal thickness at the fovea prior to oral caffeine intake was 337.00
      (IQR 83.75) MUm, which decreased to 311.00 (IQR 79.25) MUm at 1 h and 311.00 (IQR
      75.00) MUm at 3 h following oral caffeine intake (p = 0.001, 0.002,
      respectively). The median choroidal thickness was also significantly decreased
      following oral caffeine intake at other five extrafoveal points (p < 0.05 for
      all). The difference in choroidal thickness was not statistically significant
      between 1 and 3 h of caffeine intake at all six points. In the control group, the
      median baseline choroidal thickness at the fovea was 330.00 (IQR 88.75) MUm,
      which was 330.50 (IQR 80.75) MUm at 1 h and 330.50 (IQR 90.75) MUm at 3 h (p =
      0.552, 0.704, respectively). CONCLUSIONS: Caffeine causes a significant decrease
      in choroidal thickness following oral intake. This decrease might be a result of
      reduced ocular blood flow due to its vasoconstrictive effect.

PMID- 24861903
TI  - Papillary lesions of the breast: outcomes of 156 patients managed without
      excisional biopsy.
AB  - Papillomas of the breast are benign epithelial neoplasms. Because of the low, but
      continued potential for malignancy, the treatment options after initial diagnosis
      remain controversial. The aim of this study was to analyze the clinical course of
      patients with papilloma who were managed by active surveillance following initial
      diagnosis by core needle biopsy or vacuum-assisted biopsy. This retrospective
      study analyzed 174 patients with 180 papillomas that were diagnosed by core
      needle biopsy (113 cases) or vacuum-assisted biopsy (67 cases) at the Breast
      Center Seefeld Zurich between February 2002 and May 2011. We excluded 24 cases
      that underwent excisional biopsy for removal of the lesion. Over a mean follow-up
      of 3.5 years, 13 further events occurred in 156 cases (8%). These events included
      two cases of ductal carcinoma in situ (one after 4 and one after 6 years), one
      case of atypical ductal hyperplasia, one radial scar, eight cases of papilloma,
      and one case of flat epithelial atypia. No invasive carcinomas occurred during
      the follow-up period. Conservative management of 156 papillary lesions with
      removal by vacuum-assisted biopsy and surveillance was not associated with
      invasive cancer over a median follow-up of 3.5 years. Therefore, this approach
      seems to be a safe option for the clinical management of papillary lesions.

PMID- 24861904
TI  - Computer simulation studies of Abeta37-42 aggregation thermodynamics and kinetics
      in water and salt solution.
AB  - In vivo self-assembly of proteins into aggregates known as amyloids is related to
      many diseases. Although a large number of studies have been performed on the
      formation of amyloid, the molecular mechanism of polypeptide aggregation remains
      largely unclear. In this paper, we studied the aggregation of amyloid-forming
      peptide Abeta37-42 using all-atom molecular dynamics simulations. Using the
      integrated temperature sampling (ITS) simulation method, we observed the
      reversible formation of Abeta37-42 oligomers. The free-energy landscape for the
      polypeptide association was calculated, and aggregated states were then defined
      based on the landscape. To explore the kinetics and especially salt effects on
      the process of polypeptide aggregation, normal MD simulations were performed in
      pure water and NaCl solution, respectively. We then used the transition path
      theory (TPT) to analyze the transition network of polypeptide aggregation in
      solution. The dominant pathways of Abeta37-42 aggregation were found to differ
      significantly in pure water and the salt solution, indicating the change of
      molecular mechanism of polypeptide aggregation with the solution conditions. 

PMID- 24861905
TI  - Under your nose: a rare finding during dissection provides insights into
      maxillary supernumerary teeth.
AB  - BACKGROUND: A supernumerary tooth was found during anatomical dissection. The
      position of this tooth, still impacted in the maxilla, and the associated
      pathology make this a rare case. METHODS: During dissection by dental students of
      the sagittally-sectioned head of a cadaver, a supernumerary tooth was identified
      in the mid-palatal area. Further dissection revealed a swelling with a thin bony
      covering related to the crown of the tooth. The maxilla was removed en bloc and
      radiographic examination, CT scanning, electron microscopy and histology were
      undertaken. RESULTS: The tooth had a crenulated occlusal surface and a single
      root. It was 25 mm posterior to the root apex of the permanent upper central
      incisor. The swelling, confirmed by radiographs and CT imaging to be associated
      with the crown, occupied approximately one-third of the maxillary sinus. The 3D
      shape of the cystic lesion was visualized by a composite digital movie.
      CONCLUSIONS: The crown form, position of the tooth and the associated dentigerous
      cyst suggested it was a palatally developing supernumerary premolar which had
      been displaced to the palatal midline by the expanding cyst. This rare case
      highlights the learning and teaching opportunities available during dissection,
      showing important variations in both development and clinical anatomy.

PMID- 24861906
TI  - Diet-quality scores and risk of hip fractures in elderly urban Chinese in
      Guangdong, China: a case-control study.
AB  - This case-control study compared the associations of four widely used diet
      quality scoring systems with the risk of hip fractures and assessed their utility
      in elderly Chinese. We found that individuals avoiding a low-quality diet have a
      lower risk of hip fractures in elderly Chinese. INTRODUCTION: Few studies
      examined the associations of diet-quality scores on bone health, and no studies
      were available in Asians and compared their validity and utility in a study. We
      assessed the associations and utility of four widely used diet-quality scoring
      systems with the risk of hip fractures. METHODS: A case-control study of 726
      patients with hip fractures (diagnosed within 2 weeks) aged 55-80 years and 726
      age- (within 3 years) and gender-matched controls was conducted in Guangdong,
      China (2009-2013). Dietary intake was assessed using a 79-item food frequency
      questionnaire with face-to-face interviews, and the Healthy Eating Index-2005
      (HEI-2005, 12 items), the alternate Healthy Eating Index (aHEI, 8 items), the
      Diet Quality Index-International (DQI-I, 17 items), and the alternate
      Mediterranean Diet Score (aMed, 9 items) (the simplest one) were calculated.
      RESULTS: All greater values of the diet-quality scores were significantly
      associated with a similar decreased risk of hip fractures (all p trends <0.001).
      The multivariate-adjusted odds ratios (ORs) and 95% confidential intervals (95%
      CIs) comparing the extreme groups of diet-quality scores were 0.29 (0.18, 0.46)
      (HEI-2005), 0.20 (0.12, 0.33) (aHEI), 0.25 (0.16, 0.39) (DQI-I), and 0.28 (0.18,
      0.43) (aMed) in total subjects; and the corresponding ORs ranged from 0.04 to
      0.27 for men and from 0.26 to 0.44 for women (all p trends <0.05), respectively.
      CONCLUSIONS: Avoiding a low-quality diet is associated with a lower risk of hip
      fractures, and the aMed score is the best scoring system due to its equivalent
      performance and simplicity for the user.

PMID- 24861909
TI  - Albiglutide: first global approval.
AB  - Albiglutide (Eperzan(r) [EU]; TanzeumTM [US]), a glucagon-like peptide 1 receptor
      agonist, has been developed by GlaxoSmithKline for the treatment of type 2
      diabetes mellitus (T2DM). Albiglutide has received its first global approval in
      this indication in the EU, for use in combination with other antihyperglycaemic
      agents, including basal insulin, when these drugs and diet and exercise do not
      provide adequate glycaemic control, and as monotherapy in patients unable to take
      metformin due to contraindications or intolerance when diet and exercise alone do
      not provide adequate glycaemic control. Albiglutide has subsequently been
      approved for the second-line or later treatment of T2DM as an adjunct to diet and
      exercise in the US. This article summarizes the milestones in the development of
      albiglutide leading to this first approval for the treatment of T2DM. 

PMID- 24861907
TI  - Effects of low intensity vibration on bone and muscle in rats with spinal cord
      injury.
AB  - Spinal cord injury (SCI) causes rapid and marked bone loss. The present study
      demonstrates that low-intensity vibration (LIV) improves selected biomarkers of
      bone turnover and gene expression and reduces osteoclastogenesis, suggesting that
      LIV may be expected to benefit to bone mass, resorption, and formation after SCI.
      INTRODUCTION: Sublesional bone is rapidly and extensively lost following spinal
      cord injury (SCI). Low-intensity vibration (LIV) has been suggested to reduce
      loss of bone in children with disabilities and osteoporotic women, but its
      efficacy in SCI-related bone loss has not been tested. The purpose of this study
      was to characterize effects of LIV on bone and bone cells in an animal model of
      SCI. METHODS: The effects of LIV initiated 28 days after SCI and provided for 15
      min twice daily 5 days each week for 35 days were examined in female rats with
      moderate severity contusion injury of the mid-thoracic spinal cord. RESULTS: Bone
      mineral density (BMD) of the distal femur and proximal tibia declined by 5 % and
      was not altered by LIV. Serum osteocalcin was reduced after SCI by 20 % and was
      increased by LIV to a level similar to that of control animals. The
      osteoclastogenic potential of bone marrow precursors was increased after SCI by
      twofold and associated with 30 % elevation in serum CTX. LIV reduced the
      osteoclastogenic potential of marrow precursors by 70 % but did not alter serum
      CTX. LIV completely reversed the twofold elevation in messenger RNA (mRNA) levels
      for SOST and the 40 % reduction in Runx2 mRNA in bone marrow stromal cells
      resulting from SCI. CONCLUSION: The findings demonstrate an ability of LIV to
      improve selected biomarkers of bone turnover and gene expression and to reduce
      osteoclastogenesis. The study indicates a possibility that LIV initiated earlier
      after SCI and/or continued for a longer duration would increase bone mass.

PMID- 24861910
TI  - Antiplatelet therapy during perioperative period: double-edged sword.

PMID- 24861908
TI  - Calcium kinetics during bed rest with artificial gravity and exercise
      countermeasures.
AB  - We assessed the potential for countermeasures to lessen the loss of bone calcium
      during bed rest. Subjects ingested less calcium during bed rest, and with
      artificial gravity, they also absorbed less calcium. With exercise, they excreted
      less calcium. To retain bone during bed rest, calcium intake needs to be
      maintained. INTRODUCTION: This study aims to assess the potential for artificial
      gravity (AG) and exercise (EX) to mitigate loss of bone calcium during space
      flight. METHODS: We performed two studies: (1) a 21-day bed rest (BR) study with
      subjects receiving 1 h/day AG (n = 8) or no AG (n = 7) and (2) a 28-day BR study
      with 1 h/day resistance EX (n = 10) or no EX (n = 3). In both studies, stable
      isotopes of Ca were administered orally and intravenously, at baseline and after
      10 days of BR, and blood, urine, and feces were sampled for up to 14 days post
      dosing. Tracers were measured using thermal ionization mass spectrometry. Data
      were analyzed by compartmental modeling. RESULTS: Less Ca was absorbed during BR,
      resulting in lower Ca balance in BR+AG (-6.04 +/- 3.38 mmol/day, P = 0.023).
      However, Ca balance did not change with BR+EX, even though absorbed Ca decreased
      and urinary Ca excretion increased, because endogenous excretion decreased, and
      there was a trend for increased bone deposition (P = 0.06). Urinary N-telopeptide
      excretion increased in controls during BR, but not in the EX group. Markers of
      bone formation were not different between treatment groups for either study. Ca
      intake decreased during BR (by 5.4 mmol/day in the AG study and 2.8 mmol/day in
      the EX study), resulting in lower absorbed Ca. CONCLUSIONS: During BR (or space
      flight), Ca intake needs to be maintained or even increased with countermeasures
      such as exercise, to enable maintenance of bone Ca.

PMID- 24861911
TI  - Heart attacks triggered by huge mud slides in mountain regions and severe
      flooding in inhabited areas.
AB  - BACKGROUND: On July 12, 2012, heavy rains struck southwest Japan, particularly in
      the Mount Aso area. Huge mud slides in the mountains destroyed houses, and heavy
      rains caused severe flooding in the inhabited areas. We investigated the
      incidence of cardiovascular events after the disaster. METHODS: We investigated
      patients who were admitted to the emergency department (ED) from July 12 to
      August 31 in 2012. We reviewed all patients with cardiovascular events, including
      acute myocardial infarction (AMI), angina attack, worsening of congestive heart
      failure (CHF), cardiopulmonary arrest (CPA), arrhythmias, tako-tsubo
      cardiomyopathy (TC), and symptomatic venous thromboembolism (VTE). RESULTS: The
      total number of cardiovascular events was 28 (14 supraventricular arrhythmias, 3
      angina attacks, 1 AMI, 1 VTE, 4 CHF, 1 TC and 4 CPA). There was a significant
      increase in cardiovascular events during the follow-up period in 2012 in
      comparison with the average number of these events over the same time period
      during the prior 2 years (16.8 vs. 5.1/month, p<0.01). There was a sharp increase
      in cardiovascular events in the first week after the disaster. A second peak was
      observed 7 weeks after the disaster. Two patients with angina attack were
      previously diagnosed as having vasospastic angina. The incidence rate of AMI did
      not increase. CONCLUSION: An increase in cardiovascular events was observed after
      severe rainfalls and mud slides. Prevention of disaster-induced cardiovascular
      events should be a priority regardless of the magnitude of the disaster.

PMID- 24861912
TI  - Temporal change of enhancement after gadolinium injection on contrast-enhanced
      CMR in reperfused acute myocardial infarction.
AB  - BACKGROUND: A recent report demonstrated that early enhancement on contrast
      enhanced cardiac magnetic resonance (CE-CMR) correlated with myocardial edema
      detected by T2-weighted CMR in reperfused acute myocardial infarction (AMI).
      However, the time at which the enhancement in salvaged myocardium disappears is
      yet to be determined. We aimed to examine the time course of the enhancement with
      the use of different quantification techniques and to compare the extent of
      enhancement with the myocardial edema. METHODS AND RESULTS: CE-CMR was performed
      at 2-20 min after gadolinium administration in 32 AMI patients. The extent of
      enhancement (% myocardium) was quantified by manual delineation and the threshold
      methods of 2-5 SDs above remote myocardium. In subendocardial infarct, the
      enhancement was greatest at 2 min regardless of the quantification techniques and
      decreased with time, particularly in the first 6 min. In transmural infarct, the
      change in the size of enhancement was modest although the time course of
      enhancement varied according to the quantification techniques. The sizes of
      enhancement were not significantly different between 15 and 20 min regardless of
      the techniques and infarct transmurality. The best agreement with myocardial
      edema was found at 2 min with average differences of 0.5% and -1.2% and limits of
      agreement of +/-20.2% and +/-21.2% for the manual and 2-SD techniques,
      respectively. CONCLUSIONS: The optimal timing for delineation of salvaged
      myocardium on CE-CMR is at 2min when the manual or 2-SD technique was employed.
      Imaging needs to be completed in a short time (ideally within a minute) because
      of rapid reduction of enhancement in salvaged myocardium.

PMID- 24861913
TI  - Prevalence of subclinical coronary artery disease in ischemic stroke patients.
AB  - BACKGROUND: Recently, ischemic stroke has emerged as a new coronary artery
      disease (CAD) risk equivalent. Our purpose is to study the prevalence of CAD in
      ischemic stroke patients compared with that in non-stroke patients. METHODS AND
      RESULTS: We measured coronary calcium score (CCS) in 151 ischemic stroke patients
      without known CAD (stroke group) and compared it with 151 age- and sex-matched
      non-stroke patients (control group). CCS was significantly higher in the stroke
      group than in the control group (stroke group, median: 64, interquartile range: 3
      382 vs. control group, median: 3, interquartile range: 0-65, p<0.0001). High-risk
      CAD, defined as a CCS>=400, was detected in 24.5% of the stroke group compared
      with 9.3% of the control group (p<0.0001). Agreement between the Framingham risk
      score and CCS was found in only 62 patients (41.1%). In a multiple logistic
      regression analysis, age [hazard ratio (HR) 1.09, 95% confidence interval (CI)
      1.03-1.14], diabetes (HR 2.97, 95%CI 1.52-5.78), stroke (HR 3.85, 95%CI 1.89
      7.81), and male sex (HR 4.41, 95%CI 1.82-0.75) were significantly associated with
      high-risk CAD (p<0.001). CONCLUSIONS: Our results show that the prevalence of
      subclinical CAD in ischemic stroke patients was high, and that a quarter of them
      had high-risk CAD. Age, diabetes, stroke, and male sex were independent
      predictors of high-risk CAD.

PMID- 24861914
TI  - Maternal smoking in pregnancy and risk for congenital malformations: results of a
      Danish register-based cohort study.
AB  - OBJECTIVE: To examine the association between maternal smoking during pregnancy
      and risk for congenital malformations. DESIGN: Population-based prospective
      cohort study. SETTING: Denmark. POPULATION: A total of 838 265 singleton liveborn
      babies delivered in Denmark between 1997 and 2010 and registered in the Danish
      Medical Birth Register containing detailed information on smoking during
      pregnancy and congenital malformations. METHODS: Associations [odds ratios (OR)
      with 95% CI] between maternal smoking and risk for various groups of congenital
      malformations, investigated using the generalized estimating equation for binary
      outcomes, with adjustment for potential confounders. MAIN OUTCOME MEASURES:
      Groups of congenital malformations. RESULTS: Ever smoking during pregnancy did
      not increase the overall risk for congenital malformations, but increased risks
      were observed for multiple malformations (i.e. when two or more malformations are
      diagnosed in a child) (odds ratio 1.06, 95% confidence interval 1.01-1.10) and
      various main groups of congenital malformations including the cardiovascular
      system (odds ratio 1.13, 95% confidence interval 1.07-1.19), the respiratory
      system (odds ratio 1.25, 95% confidence interval 1.11-1.41), the digestive system
      (odds ratio 1.15, 95% confidence interval 1.07-1.24) and oral clefts (odds ratio
      1.29, 95% confidence interval 1.14-1.46), as well as for some specific congenital
      malformations including cardiac septal defects, malformations of the pulmonary
      and tricuspid valves, malformations of the great arteries, pyloric stenosis and
      clubfoot. Infants of women who quit smoking during the first two trimesters had
      no increased risk for most groups of congenital malformations. CONCLUSIONS:
      Maternal smoking increases the risk for a number of congenital malformations.
      Future smoking cessation programs should focus on this adverse health aspect in
      order to encourage more women to quit smoking before or in early pregnancy.

PMID- 24861915
TI  - Investigation of the association of hRRM1 and p53R2 gene polymorphisms in head
      and neck squamous cell carcinomas.
AB  - Head and neck squamous epithelial cell cancer (HNSCC), the world's fifth most
      common type of cancers, is associated with short life expectancy and high death
      rates if not detected in early stages. The aim of this study was to investigate
      hRRM1 and p53R2 gene polymorphisms by using real-time PCR technique in patients
      with head and neck cancer. In total, 87 patients with head and neck malignancies
      and 87 control group who have not any malignancies were included in the study
      between January 2011 and February 2012 in Istanbul University Faculty of Medicine
      Department of ORL. In the study, real-time PCR was used to detect hRRM1
      (rs12806698 C/A) and p53R2 (rs2290707 G/T) gene polymorphisms in Turkish HNSCC
      patients and healthy individuals. Genomic DNA isolation was performed according
      to the kit protocol with spin column. LightCycler 1.5 system was used to perform
      SNP genotyping using hybridization probes consisting of 3'-fluorescein and a 5'
      LightCycler Red labeled pair of oligonucleotide probes. There were significant
      differences in the distribution of hRRM1 genotypes. Frequency of individuals with
      hRRM1 AA genotype was higher in patients with less differentiation when compared
      with well differentiation [p 0.025, Fisher's exact test, odds ratio (OR) 0.140,
      95 % confidence intervals (CI) 0.024-0.797]. It is observed that A allele
      carriers have nearly twofold risk for development of the disease (p = 0.022; chi
      (2) 5.24; OR 2.02, 95 % CI 1.10-3.72).

PMID- 24861916
TI  - Chemotherapy alleviates subacute recurrent glioma-associated refractory cerebral
      edema by downregulating vascular endothelial growth factor.
AB  - To identify a novel treatment modality for postoperative, glioma-related
      refractory cerebral edema (RCE), eight patients with postoperative RCE received
      chemotherapy between January 2008 and July 2012 were enrolled. There were five
      males and three females aged between 24 and 65 years (mean 45.7 years). Vascular
      endothelial growth factor (VEGF) levels in the cerebrospinal fluid were measured
      by enzyme-linked immuno-sorbent assay pre- and postchemotherapy. After 3 days
      postchemotherapy, midline shift improved from 13.14 +/- 0.65 to 7.21 +/- 0.55 mm
      and compressed or effaced basilar cisterns disappeared based on cranial computed
      tomographic scans. Glascow Coma Scale scores in patients significantly improved
      from 11.13 +/- 0.52 to 14.50 +/- 0.27 after chemotherapy. Two patients developed
      grade 1 leukopenia after 3 weeks, and one patient had grade 1 thrombocytopenia 2
      weeks after chemotherapy. No fatal complications occurred. The edematous volume
      reduced from 77,074 +/- 6,813 to 27,874 +/- 5,073 mm(3) (p < 0.001). VEGF levels
      were significantly downregulated after chemotherapy (from 543.8 +/- 76.39 to
      122.2 +/- 59.30 pg/ml, p < 0.001). Chemotherapy may serve to alleviate glioma
      related RCE by reducing VEGF levels, especially in patients who were insensitive
      to decompressive craniectomy.

PMID- 24861917
TI  - Mutations of KRAS and PIK3CA as independent predictors of distant metastases in
      colorectal cancer.
AB  - The objective was to evaluate DNA mutations of KRAS, BRAF, and PIK3CA and their
      clinicopathological correlations with colorectal cancer (CRC) and to identify
      their contribution to distant metastases in CRC. A total of 148 tumor samples
      were obtained from patients with CRC in the Shandong Tumor Hospital and Institute
      between January 2008 and December 2009. DNA was extracted for polymerase chain
      reaction amplification and pyrosequencing to evaluate mutations of KRAS, BRAF,
      and PIK3CA, and clinicopathological correlations of these mutations with CRC
      [including age, gender, tumor location, pathological type, tumor-node-metastasis
      (TNM) classification, and distant metastatic status] were analyzed. KRAS, BRAF,
      and PIK3CA mutation rates were identified in 46 (31.1 %), 11 (7.4 %), and 14 (9.5
      %) of the total 148 CRC tumor samples, respectively. Neither mutation had
      significant correlation with age, gender, size and location of the tumor, and
      pathological type. KRAS, BRAF, and PIK3CA mutations were found in 14 (66.7 %), 3
      (14.3 %), and 8 (38.1 %) of the 21 distant metastatic colorectal tumor samples,
      respectively. The relative risks of distant metastasis for KRAS, BRAF, and PIK3CA
      mutations were 30.4 versus 6.8 % (P = 0.001), 27.3 versus 13.1 % (P = 0.191), and
      57.1 versus 9.7 % (P < 0.001) (5-year risks), respectively. Patients with either
      KRAS or PIK3CA mutations are more susceptible to distant metastasis. Thus, these
      two mutations might be used as independent predictors of distant metastatic CRC.

PMID- 24861918
TI  - Genetic polymorphisms of TERT and CLPTM1L and risk of lung cancer: a case-control
      study in northeast Chinese male population.
AB  - Recently, some genome-wide association studies have implicated telomerase reverse
      transcriptase (TERT) and cleft lip and palate transmembrane 1-like gene (CLPTM1L)
      in lung cancer development. Here, we present a case-control study that evaluates
      the genetic effects of TERT-rs2736098 and CLPTM1L-rs401681 variants on the risk
      of lung cancer development in a Chinese male population. We found that the
      homozygous variant genetic model of the TERT gene was associated with a
      significantly increased risk of lung cancer with an adjusted odds ratio (OR) of
      1.988. The TERT-rs2736098 T allele was also associated with increased lung cancer
      risk both in adenocarcinoma and squamous cell carcinoma. No association was found
      between CLPTM1L-rs401681 and lung cancer risk. However, the joint effect of TERT
      and CLPTM1L variants increased the risk of lung cancer, especially squamous cell
      carcinoma, with an adjusted OR of 3.274. However, the exact functional effect of
      these two variant genes remains unclear, and further investigation is needed in
      the future. 

PMID- 24861920
TI  - Value of fibrinogen and D-dimer in predicting recurrence and metastasis after
      radical surgery for non-small cell lung cancer.
AB  - Previous studies have suggested an association between preoperative plasma
      fibrinogen and D-dimer levels and prognosis in patients with non-small cell lung
      cancer (NSCLC) who underwent surgery. In this study, we evaluate the value of pre
      and post-operative plasma fibrinogen and D-dimer levels and changes in the
      levels of the two markers between before and after operation in predicting tumor
      recurrence and metastasis in NSCLC patients who undergoing radical surgery. One
      hundred and eighty-four patients with I-IIIA NSCLC were enrolled in this study,
      and plasma fibrinogen and D-dimer levels were measured in these patients before
      and after surgery, respectively. The results showed that pre- and post-operative
      plasma fibrinogen and D-dimer levels were significantly higher in NSCLC patients
      than in control group. Pre- and post-operative plasma fibrinogen and D-dimer
      positivities were significantly correlated with tumor recurrence (P = 0.020 and P
      = 0.001 for fibrinogen, and P = 0.027 and P = 0.001 for D-dimer). Moreover, there
      was a significant link between the decrease in fibrinogen and D-dimer levels
      after surgery and tumor recurrence (P = 0.014 and P = 0.018). Patients with pre-
      and post-operative fibrinogen and D-dimer positivities had a shorter disease-free
      survival (DFS) than those without (P = 0.002 and P < 0.001 for fibrinogen, and P
      = 0.003 and P = 0.001 for D-dimer). Multivariate Cox regression analyses revealed
      that pre- and post-operative fibrinogen and D-dimer positivities were independent
      predictors for unfavorable DFS. Our results indicate that pre- and post-operative
      plasma fibrinogen and D-dimer levels may be useful biomarkers in predicting tumor
      recurrence and metastasis for patients who undergo curative surgery.

PMID- 24861919
TI  - TGF-beta1-induced expression of Id-1 is associated with tumor progression in
      gastric cancer.
AB  - Transforming growth factor beta1 (TGF-beta1) and inhibitor of differentiation/DNA
      binding 1 (Id-1) have been shown to be associated with aggressive metastatic
      behavior of cancer cells in many malignant tumors. However, their role in gastric
      cancer (GC) has not been established. In this study, we investigated the
      relationship between expression of Id-1 and TGF-beta1 in GC as well as their
      association with GC progression. The immunohistochemical analysis of 71 human GC
      samples indicated that both Id-1 and TGF-beta1 were markedly upregulated in tumor
      tissue compared with the adjacent tissue; in addition, a significant positive
      correlation was found between the expression levels of Id-1 and TGF-beta1 by
      Pearson's correlation analysis. Furthermore, the investigation of the association
      of Id-1 and TGF-beta1 with patient clinical characteristics revealed that Id-1
      expression was significantly correlated with tumor differentiation, while TGF
      beta1 was associated with lymph node metastasis. The results were validated in
      vitro by using a GC cell line, AGS. The expression of Id-1 was upregulated at 24
      and 48 h after the treatment with TGF-beta1, whereas it did not affect the
      proliferation of cells. TGF-beta1 also influenced the expression of N-cadherin
      and beta-catenin. Our results suggested that Id-1 and TGF-beta1 played important
      roles in the progression of GC, in which Id-1 might act as a downstream mediator
      of TGF-beta1 signaling through a regulatory mechanism involving N-cadherin and
      beta-catenin. The TGF-beta1/Id-1 axis might serve as a future therapeutic target
      for GC. 

PMID- 24861921
TI  - KAP-1 is overexpressed and correlates with increased metastatic ability and
      tumorigenicity in pancreatic cancer.
AB  - This study aimed to investigate the role in metastasis and prognostic value of
      KAP-1 in pancreatic cancer (PC). The expression of KAP-1 was analyzed by
      quantitative real-time polymerase chain reaction, Western blotting, and
      immunohistochemical staining in 91 human PC tissue samples. Capan-2 cells were
      transfected with a lentiviral vector expressing KAP-1 (Capan-2/KAP-1) or the
      empty vector (Capan-2/vector); cell migration and invasion were assayed in vitro
      using Transwell migration and wound-healing assays, and in vivo using a xenograft
      model in nude mice. KAP-1 was found to be overexpressed in human PC, and the
      expression of KAP-1 correlated with clinical stage. Overexpression of KAP-1
      increased the invasion and migration of Capan-2 cells in vitro. Furthermore,
      overexpression of KAP-1 promoted the growth and metastatic ability of PC cells in
      a xenograft model in nude mice. Moreover, overexpression of KAP-1 induced the
      epithelial-mesenchymal transition (EMT) in PC cells both in vitro and in vivo, as
      indicated by increased expression of mesenchymal markers such as vimentin and
      decreased expression of E-cadherin. This study indicates that KAP-1 may promote
      metastasis in PC by regulating the EMT and suggests that KAP-1 may have potential
      as a predictor of metastasis in patients with pancreatic cancer. 

PMID- 24861922
TI  - Expression and correlation of matrix metalloproteinase-9 and heparanase in
      patients with breast cancer.
AB  - Matrix metalloproteinase-9 (MMP-9) and heparanase (HPSE) are thought to be
      involved in tumor progression and metastasis. However, up to now, there are no
      studies that simultaneously investigated the expression levels of MMP-9 and HPSE
      in tumor tissue and serum of breast cancer patients. Their correlation in breast
      cancer pathological processes is unknown. The purpose of this study was to
      investigate the expression profile of MMP-9 and HPSE in breast cancer and to
      assess their clinicopathological significance. We measured serum MMP-9 and HPSE
      by enzyme-linked immunosorbent assay in healthy women, and in patients with
      benign and malignant breast disease. We also evaluated the expression of MMP-9
      and HPSE protein in paraffin-embedded tumor tissues by immunohistochemistry. We
      then correlated serum and tissue levels of MMP-9 and HPSE in breast cancer
      samples and their expression with patients' clinicopathologic characteristics. We
      found that serum levels of MMP-9 and HPSE were significantly higher in breast
      cancer patients than in benign breast disease and in healthy controls (P =
      0.001). There was positive correlation between MMP-9 and HPSE in breast cancer
      patients. The tissue and serum levels of MMP-9 were associated with histology
      grade, lymph node status, pathological stage, and lymphovascular invasion (all P
      < 0.05). The tissue levels of MMP-9 were also associated with ER (P = 0.038) and
      Ki-67 (P = 0.032). The tissue and serum levels of HPSE expression were associated
      with tumor size, histology grade, lymph node status, and pathological stage (all
      P < 0.05). Our findings suggested that MMP-9 and HPSE might further be evaluated
      as biomarkers for predicting progression and prognosis of breast cancer.

PMID- 24861925
TI  - Impacts of autonomy-supportive versus controlling instructional language on motor
      learning.
AB  - The authors examined the influence of autonomy-supportive (ASL), controlling
      (CL), and neutral instructional language (NL) on motor skill learning (cricket
      bowling action). Prior to and several times during the practice phase,
      participants watched the same video demonstration of the bowling action but with
      different voice-over instructions. The instructions were designed to provide the
      same technical information but to vary in terms of the degree of choice
      performers would perceive when executing the task. In addition to measurements of
      throwing accuracy (i.e., deviation from the target), perceived choice, self
      efficacy, and positive and negative affect were assessed at the end of the
      practice phase and after a retention test without demonstrations and instructions
      on Day 2. ASL resulted in perceptions of greater choice, higher self-efficacy,
      and more positive affect during practice than CL, and enhanced learning as
      demonstrated by retention test performance. Thus, granting learners autonomy
      appeared to endow them with confidence in their ability, diminished needs for
      control of negative emotional responses, and created more positive affect, which
      may help consolidate motor memories. 

PMID- 24861924
TI  - Sex chromosome complement influences operant responding for a palatable food in
      mice.
AB  - The procurement and consumption of palatable, calorie-dense foods is influenced
      by the nutritional and hedonic value of foods. Although many factors can
      influence the control over behavior by foods rich in sugar and fat, emerging
      evidence indicates that biological sex may play a particularly crucial role in
      the types of foods individuals seek out, as well as the level of motivation
      individuals will exert to obtain those foods. However, a systematic investigation
      of food-seeking and consumption that disentangles the effects of the major sex
      biasing factors, including sex chromosome complement and organizational and
      activational effects of sex hormones, has yet to be conducted. Using the four
      core genotypes mouse model system, we separated and quantified the effects of sex
      chromosome complement and gonadal sex on consumption of and motivation to obtain
      a highly palatable solution [sweetened condensed milk (SCM)]. Gonadectomized mice
      with an XY sex chromosome complement, compared with those with two X chromosomes,
      independent of gonadal sex, appeared to be more sensitive to the reward value of
      the SCM solution and were more motivated to expend effort to obtain it, as
      evidenced by their dramatically greater expended effort in an instrumental task
      with progressively larger response-to-reward ratios. Gonadal sex independently
      affected free consumption of the solution but not motivation to obtain it. These
      data indicate that gonadal and chromosomal sex effects independently influence
      reward-related behaviors, contributing to sexually dimorphic patterns of behavior
      related to the pursuit and consumption of rewards. 

PMID- 24861926
TI  - Photoprotective mechanism of the non-target organism Arabidopsis thaliana to
      paraquat exposure.
AB  - The response of photosystem II (PSII), of the non-target organism Arabidopsis
      thaliana, to paraquat (Pq) exposure was studied by chlorophyll fluorescence
      imaging. Effects of 1mM Pq application by spray on A. thaliana leaves were
      monitored as soon as 20min after application at the deposit areas of the
      droplets. A decline in the effective quantum yield of photochemical energy
      conversion in PSII (PhiPSII) was accompanied by an increase in the quantum yield
      for dissipation by down regulation in PSII (PhiNPQ). The concomitant decrease in
      the quantum yield of non-regulated energy loss in PSII (PhiNO) pointed out a
      quick effective photoprotection mechanism to Pq exposure. Even 1h after Pq spray,
      when the maximum Pq effect was observed, the decrease of electron transport rate
      (ETR) and the increase in non-photochemical quenching (NPQ) resulted to maintain
      almost the same redox state of quinone A (QA) as control plants. Thus, maximal
      photoprotection was achieved since NPQ was regulated in such a way that PSII
      reaction centers remained open. Arabidopsis plants were protected from Pq
      exposure, by increasing NPQ that dissipates light energy and decreases the
      efficiency of photochemical reactions of photosynthesis (down regulation of PSII)
      via the "water-water cycle". PSII photochemistry began to recover 4h after Pq
      exposure, and this was evident from the increase of PhiPSII, the simultaneous
      decrease of PhiNPQ, and the concomitant decrease of PhiNO. Yet, ETR began to
      increase, as well as the fraction of open PSII reaction centers.

PMID- 24861923
TI  - Regulation of cellular iron metabolism and its implications in lung cancer
      progression.
AB  - Iron is essential for life and is involved in numerous metabolic processes
      including cell growth and proliferation. However, excess iron in the body raises
      the risk of developing cancer due to its capacity to engage in redox cycling and
      free radical production. Therefore, iron can contribute to both carcinogenesis
      and tumor growth. Both epidemiologic and laboratory studies have demonstrated
      that the effects of iron overload are associated with the tumorigenesis of lung
      cancer and growth of lung cancer cells. In particular, the discovery of hepcidin
      and several iron transporters in the past decade may warrant reconsideration of
      the role of iron in carcinogenesis and tumor cell proliferation in lung cancer.
      Pathways of iron uptake, storage, efflux, and regulation are all disturbed in
      cancer, suggesting that reprogramming of iron metabolism is a critical aspect of
      tumor cell survival. Although these pathways in lung cancer have been identified
      and extensively studied, many issues on the metabolic processes of iron in lung
      cancer cells have not been addressed. Targeting metabolic pathways of iron may
      provide new tools for lung cancer prognosis and therapy. 

PMID- 24861927
TI  - Molecular basis for resistance to ACCase-inhibiting fluazifop in Eleusine indica
      from Malaysia.
AB  - Eleusine indica (goosegrass) populations resistant to fluazifop, an acetyl-CoA
      carboxylase (ACCase: EC6.4.1.2)-inhibiting herbicide, were found in several
      states in Malaysia. Dose-response assay indicated a resistance factor of 87.5,
      62.5 and 150 for biotypes P2, P3 and P4, respectively. DNA sequencing and allele
      specific PCR revealed that both biotypes P2 and P3 exhibit a single non
      synonymous point mutation from TGG to TGC that leads to a well known Trp-2027-Cys
      mutation. Interestingly, the highly resistant biotype, P4, did not contain any of
      the known mutation except the newly discovered target point Asn-2097-Asp, which
      resulted from a nucleotide change in the codon AAT to GAT. ACCase gene expression
      was found differentially regulated in the susceptible biotype (P1) and highly
      resistant biotype P4 from 24 to 72h after treatment (HAT) when being treated with
      the recommended field rate (198gha(-1)) of fluazifop. However, the small and
      erratic differences of ACCase gene expression between biotype P1 and P4 does not
      support the 150-fold resistance in biotype P4. Therefore, the involvement of the
      target point Asn-2097-Asp and other non-target-site-based resistance mechanisms
      in the biotype P4 could not be ruled out.

PMID- 24861928
TI  - Induction of systemic resistance against tobacco mosaic virus by Ningnanmycin in
      tobacco.
AB  - Ningnanmycin (NNM) is an antiviral agent firstly isolated from Strepcomces
      noursei var.xichangensisn. Studies have shown that NNM promotes PAL, POD and SOD
      activity and possesses antiviral activity against tobacco mosaic virus (TMV). In
      this study, our results demonstrated that NNM inhibited the polymerization
      process of TMV coat protein (TMV-CP) in vitro and promoted the systemic
      accumulation of pathogenesis-related proteins (PRs), which are the markers of
      systemic acquired resistance (SAR). An non-expressor, pathogenesis-related genes
      1 (NPR1) that regulates SAR and induces systemic resistance (ISR), increased. In
      addition, the Jaz3 expression increase showed that NNM also induced ISR. Based on
      the results of this work and earlier reports, it is suggesting that NNM induces
      tobacco systemic resistance against TMV via activating multiple plant defense
      signaling pathways.

PMID- 24861929
TI  - Metabolic responses in root nodules of Phaseolus vulgaris and Vicia sativa
      exposed to the imazamox herbicide.
AB  - Alterations on growth, amino acids metabolism and some antioxidant enzyme
      activities as result of imazamox treatment were examined in determinate and
      indeterminate nodules, formed by Phaseolus vulgaris and Vicia sativa,
      respectively. Young seedlings of both legumes were inoculated with their
      respective microsymbionts and grown under controlled conditions. At vegetative
      growth, plants were treated with imazamox (250MUM) in the nutrient solution and
      harvested 7days after. Imazamox was mainly accumulated in V. sativa where
      concentrations were more than six fold higher than those detected in P. vulgaris.
      Nodule dry weight and total nitrogen content were reduced by the herbicide
      treatment: the highest decrease of nodule biomass (50%) and nitrogen content
      (40%) were registered in V. sativa and P. vulgaris, respectively. The
      concentration of branched-chain amino acids (BCAA) did not change in neither
      determinate nor indeterminate nodules even though the acetohydroxyacid synthase
      activity decreased in root and nodules of both symbioses with the herbicide
      application. Based on this last result and taking into account that total free
      amino acids increased in roots but not in nodules of common vetch, a possible
      BCAA translocation from root to nodule could occur. Our results suggest that the
      maintenance of BCAA balance in nodule become a priority for the plant in such
      conditions. The involvement of activities glutathione-S-transferase, guaiacol
      peroxidase and superoxide dismutase in the response of the symbioses to imazamox
      are also discussed.

PMID- 24861930
TI  - Resistance selection and biochemical mechanism of resistance against cyflumetofen
      in Tetranychus cinnabarinus (Boisduval).
AB  - The carmine spider mite, Tetranychus cinnabarinus is an important crop and
      vegetable plants pest mite. As a novel acaricide, cyflumetofen is effective
      against Tetranychus and Panonychus mites, but its risk and biochemical mechanism
      of resistance in mites is not clear. In this study, the resistance against
      cyflumetofen was selected and its biochemical mechanisms were studied in T.
      cinnabarinus. After selection the susceptibility and resistance against
      cyflumetofen in T. cinnabarinus, the final resistance ratio reached 21.33 at LC50
      (CyR-43/CyS). All the collected field populations showed low resistance against
      cyflumetofen, although it had never been used in China. The activity of
      detoxifying enzymes CarE, MFO and GSTs were significantly increased in the final
      selected resistance strain (CyR-43), especially that for GSTs increased more than
      7-folds after selection. The resistance against cyflumetofen developed slowly
      when selected from the susceptible strain in laboratory, but the resistant genes
      already existed in field populations, and the GSTs was the most important
      detoxifying enzyme conferring resistance against cyflumetofen in T. cinnabarinus.
      These results would provide the valuable information for designing appropriate
      strategies for the practical application of cyflumetofen in the field and
      delaying resistance development.

PMID- 24861931
TI  - Life table study of the effects of sublethal concentrations of thiamethoxam on
      Bradysia odoriphaga Yang and Zhang.
AB  - Bradysia odoriphaga Yang and Zhang (chive gnat) is the major insect pest
      affecting Chinese chive in Northern China. In order to explore the integrated
      control of B. odoriphaga, sublethal effects of the neonicotinoid insecticide
      thiamethoxam were studied. The standard contact and stomach bioassay method was
      used to assess the effects of sublethal (LC5 and LC20) concentrations of
      thiamethoxam on the demographic parameters of B. odoriphaga, and data were
      interpreted based on the age-stage, two-sex life table theory. After thiamethoxam
      treatment, the intrinsic and finite rates of increase, net reproduction rate,
      survival rate, and reproductive value were all markedly decreased, while the mean
      generation time, total preovipositional period, and larval and pupal duration
      were prolonged, compared with controls. The intrinsic rates of increase dropped
      from 0.1775/day to 0.1502-0.1136/day. Following LC5 and LC20 treatments, net
      reproduction rate dropped from 61.75 offspring/individual (control) to 43.36 and
      20.75 offspring/individual, respectively. Sublethal concentrations of
      thiamethoxam decreased the developmental rate of laboratory populations of B.
      odoriphaga, suggesting that such doses may be useful in integrated pest
      management strategies.

PMID- 24861932
TI  - Steric hindrance of 2,6-disubstituted benzoic acid derivatives on the uptake via
      monocarboxylic acid transporters from the apical membranes of Caco-2 cells.
AB  - Benzoic acid is a typical substrate for monocarboxylic acid transporters (MCTs),
      and easily taken up from the apical membranes of Caco-2 cells by MCTs. However,
      some benzoic acid derivatives were sparingly taken up by Caco-2 cells. To
      elucidate the mechanism of lower uptake of the derivatives, we investigated the
      effect of substitution of benzene ring on the uptake by MCTs using Caco-2 cells.
      Among the benzoic acid derivatives tested, the uptake of 2,6-disubstituted
      benzoic acids was markedly lower than that of other benzoic acids. Co-incubation
      of the 2,6-disubstituted derivatives with benzoic acid did not decrease the
      uptake of benzoic acid, while co-incubation with other derivatives significantly
      decreased the uptake of benzoic acid. Kinetic analyses elucidated that the uptake
      of 2,6-dichlorobenzoic acid and 2,3,6-trichlorobenzoic acid did not involve the
      carrier-mediated process. The 2,6-disubstitution of benzoic acid may prevent the
      access of carboxylic acid group to MCTs expressed on the apical membranes of Caco
      2 cells.

PMID- 24861933
TI  - Sublethal effects of the chitin synthesis inhibitor, hexaflumuron, in the cotton
      mirid bug, Apolygus lucorum (Meyer-Dur).
AB  - Hexaflumuron is a type of benzoylphenylurea insecticide which is highly toxic for
      many insects. Sublethal doses of hexaflumuron have been shown to significantly
      affect insect growth and development. However, the action mechanism of
      hexaflumuron is not well understood. In the present study, first instar Apolygus
      lucorum nymphs were exposed to sublethal doses of hexaflumuron based on the
      estimated 120h acute LC50 valve of 20.53mg/ml. We found that exposure to
      sublethal hexaflumuron doses resulted in a significant increase in development
      time and reduced the weights of fifth instar A. lucorum nymphs. We also measured
      trehalose, which is a primary blood sugar in insects, and the enzyme trehalase
      that is involved in energy metabolism. Trehalose content in first instar nymphs
      significantly increased following hexaflumuron treatment while the glucose
      content, soluble trehalase activity and expression levels of ALTre-1 mRNA
      decreased significantly. However, no significant changes in membrane-bound
      trehalase activity and ALTre-2 mRNA expression were observed. In addition, these
      decreases or increases could be correlated to increases in treatment time or
      concentration of hexaflumuron, respectively. The present findings indicated that
      sublethal doses of hexaflumuron could interfere the normal carbohydrate
      metabolism by depressing the expression of ALTre-1 in A. lucorum, which provide
      valuable information on the physiology and molecular mechanisms for the toxicity
      of hexaflumuron.

PMID- 24861934
TI  - Cypermethrin induces astrocyte damage: role of aberrant Ca(2+), ROS, JNK, P38,
      matrix metalloproteinase 2 and migration related reelin protein.
AB  - Cypermethrin is a synthetic type II pyrethroid, derived from a natural pyrethrin
      of the chrysanthemum plant. Cypermethrin-mediated neurotoxicity is well studied;
      however, relatively less is known of its effect on astrocyte development and
      migration. Astrocytes are the major components of blood brain barrier (BBB), and
      astrocyte damage along with BBB dysfunction impair the tight junction (TJ)
      proteins resulting in altered cell migration and neurodegeneration. Here, we
      studied the mechanism of cypermethin mediated rat astrocyte damage and BBB
      disruption, and determined any change in expression of proteins associated with
      cell migration. Through MTT assay we found that cypermethrin reduced viability of
      cultured rat astrocytes. Immunolabelling with astrocyte marker, glial fibrillary
      acidic protein, revealed alteration in astrocyte morphology. The astrocytes
      demonstrated an enhanced release of intracellular Ca(++) and ROS, and up
      regulation in p-JNK and p-P38 levels in a time-dependent manner. Cypermethrin
      disrupted the BBB (in vivo) in developing rats and attenuated the expression of
      the extracellular matrix molecule (ECM) and claudin-5 in cultured astrocytes. We
      further observed an augmentation in the levels of matrix metalloproteinase 2
      (MMP2), known to modulate cellular migration and disrupt the developmental ECM
      and BBB. We observed an increase in the levels of reelin, involved in cell
      migration, in cultured rat astrocytes. The reelin receptor, alpha3beta1integrin,
      and a mammalian cytosolic protein Disabled1 (Dab1) were also up-regulated.
      Overall, our study demonstrates that cypermethrin induces astrocyte injury via
      modulation in Ca(++), ROS, JNK and P38 pathways, which may alter MMP expression
      and reelin dependent astrocyte migration during brain development.

PMID- 24861935
TI  - The alpha6 nicotinic acetylcholine receptor subunit of Frankliniella occidentalis
      is not involved in resistance to spinosad.
AB  - Insects evolve resistance which constrains the sustainable use of insecticides.
      Spinosyns, a class of environmentally-friendly macrolide insecticides, is not an
      exception. The mode of inheritance and the mechanisms of resistance to spinosad
      (the most common spinosyn insecticide) in Frankliniella occidentalis (Western
      flower thrips, WFT) were investigated in this study. Resistance (170,000-fold)
      was autosomal and completely recessive. Recent studies showed that deletion of
      the nicotinic acetylcholine receptor alpha6 subunit gene resulted in strains of
      Drosophila melanogaster, Plutella xylostella and Bactrocera dorsalis that are
      resistant to spinosad, indicating that nAChRalpha6 subunit maybe important for
      the toxic action of this insecticide. Conversely, a G275E mutation of this
      subunit in F. occidentalis was recently proposed as the mechanism of resistance
      to spinosad. We cloned and characterized nAChRalpha6 from three susceptible and
      two spinosad resistant strains from China and the USA. The Foalpha6 cDNA is
      1873bp and the open reading frame is 1458bp which encodes 485 amino acid residues
      with a predicted molecular weight of 53.5-kDa, the 5' and 3' UTRs are 121 and
      294bp, respectively. There was no difference in the cDNA sequence between the
      resistant and susceptible thrips, suggesting the G275E mutation does not confer
      resistance in these populations. Ten isoforms of Foalpha6, arising from
      alternative splicing, were isolated and did not differ between the spinosad
      susceptible and resistant strains. Quantitative real time PCR analysis showed
      Foalpha6 was highly expressed in the first instar larva, pupa and adult, and the
      expression levels were 3.67, 2.47, 1.38 times that of the second instar larva.
      The expression level was not significantly different between the susceptible and
      resistant strains. These results indicate that Foalpha6 is not involved in
      resistance to spinosad in F. occidentalis from China and the USA.

PMID- 24861936
TI  - Ionizing radiation causes increased tau phosphorylation in primary neurons.
AB  - Radiotherapy is the major treatment modality for primary and metastatic brain
      tumors which involves the exposure of brain to ionizing radiation. Ionizing
      radiation can induce various detrimental pathophysiological effects in the adult
      brain, and Alzheimer's disease and related neurodegenerative disorders are
      considered to be late effects of radiation. In this study, we investigated
      whether ionizing radiation causes changes in tau phosphorylation in cultured
      primary neurons similar to that in Alzheimer's disease. We demonstrated that
      exposure to 0.5 or 2 Gy gamma rays causes increased phosphorylation of tau
      protein at several phosphorylation sites in a time- and dose-dependent manner.
      Consistently, we also found ionizing radiation causes increased activation of
      GSK3beta, c-Jun N-terminal kinase and extracellular signal-regulated kinase
      before radiation-induced increase in tau phosphorylation. Specific inhibitors of
      these kinases almost fully blocked radiation-induced tau phosphorylation. Our
      studies further revealed that oxidative stress plays an important role in
      ionizing radiation-induced tau phosphorylation, likely through the activation of
      c-Jun N-terminal kinase and extracellular signal-regulated kinase, but not
      GSK3beta. Overall, our studies suggest that ionizing radiation may cause
      increased risk for development of Alzheimer's disease by promoting abnormal tau
      phosphorylation.

PMID- 24861938
TI  - Recommendations for the characterization of immunogenicity response to multiple
      domain biotherapeutics.
AB  - Many biotherapeutics currently in development have complex mechanisms of action
      and contain more than one domain, each with a specific role or function. Examples
      include antibody-drug conjugates (ADC), PEGylated, fusion proteins and bi
      specific antibodies. As with any biotherapeutic molecule, a multi-domain
      biotherapeutic (MDB) can elicit immune responses resulting in the production of
      specific anti-drug antibodies (ADA) when administered to patients. As it is
      beneficial to align industry standards for evaluating immunogenicity of MDBs,
      this paper highlights pertinent immunogenicity risk factors and describes steps
      involved in the design of a testing strategy to detect and characterize binding
      (non-neutralizing and neutralizing, NAb) ADAs. In a common tier based approach,
      samples identified as ADA screen positive are confirmed for the binding
      specificity of the antibodies to the drug molecule via a confirmatory assay. The
      confirmation of specificity is generally considered as a critical step of the
      tier based approach in overall ADA response evaluation. Further characterization
      of domain specificity of polyclonal anti-MDB ADA response may be required based
      on the analysis of molecule specific risk factors. A risk based approach in
      evaluating the presence of NAbs for MDB is discussed in this article. Analysis of
      domain-specific neutralizing antibody reactivity should be based on the risk
      assessment as well as the information learned during binding ADA evaluation.
      Situations where additional characterization of NAb specificity is possible and
      justified are discussed. Case studies demonstrating applicability of the risk
      factor based approach are presented. In general, the presence of a domain with
      high immunogenicity risk or presence of a domain with high endogenous protein
      homology may result in an overall high immunogenicity risk level for the entire
      MDB and can benefit from domain specificity characterization of immune response.
      For low immunogenicity risk MDBs, domain specificity characterization could be re
      considered at later clinical phases based on the need to explain specific
      clinical observations. Inclusion of domain specificity characterization in early
      phase clinical studies for MDBs with limited clinical immunogenicity experience
      may be considered to help understand its value in later clinical development. It
      is beneficial and is recommended to have a well-defined plan for the
      characterization of ADA domain specificity and data analysis prior to the
      initiation of sample testing. Overall, best practices for immunogenicity
      evaluation of complex MDBs are discussed. 

PMID- 24861937
TI  - Comparative antibacterial efficacy of photodynamic therapy and ultrasonic
      irrigation against Enterococcus faecalis in vitro.
AB  - Enterococcus faecalis poses a challenge to the efficacy of traditional root canal
      disinfection methods. This study was aimed to establish a synergistic root canal
      disinfection strategy combining ultrasonic irrigation with photodynamic therapy
      (PDT) together and to test its antibacterial efficacy against E. faecalis. Twenty
      seven bovine root canals infected with E. faecalis were randomly divided into
      three groups and treated with different disinfection methods as follows:
      ultrasonic irrigation with 2.5% NaOCl, methylene blue (MB)-mediated PDT, or
      combined ultrasonic irrigation and PDT as described above. Quantification of E.
      faecalis was performed on the root canals before and immediately after the
      disinfection treatment. Residual bacteria were determined by counting colony
      forming units. Samples were randomly selected from the three groups, and the
      morphology of residual bacteria inside the dentinal tubules was studied by
      scanning electron microscopy. The number of surviving E. faecalis in the group
      treated with the combination method was significantly lower (P < 0.05) than those
      in the ultrasonic irrigation-treated or PDT-treated groups. Similar results were
      found in the morphological studies of the three groups. The results of our study
      highlighted the importance of combination of ultrasonic irrigation and PDT to
      produce significant antibacterial efficacy against E. faecalis during root canal
      disinfection. 

PMID- 24861940
TI  - What is the fate of the abstracts submitted at the French Congress of Digestive
      and Hepato-biliary Surgery?
AB  - GOAL: The aim of this study was to objectively analyze the characteristics of
      abstracts submitted to the annual joint congress of the SFCD (French Society of
      Digestive Surgery) and the ACBHT (Association of Hepato-biliary Surgery and
      Transplantation), in order to identify factors associated with acceptance for
      presentation at the Congress and of subsequent publication in a scientific
      journal. MATERIAL AND METHODS: All abstracts submitted between 2005 and 2012 were
      retrospectively reviewed. Univariate and multivariate analysis were perfomed to
      determine the factors associated with acceptance for presentation at the Congress
      and/or for subsequent publication in the medical literature (based on PubMed).
      RESULTS: The number of submissions increased from 128 in 2005 to 223 in 2012,
      i.e., an increase of 74.2%. Among the 1352 abstracts, 1106 (81.8%) were
      retrospective studies while only 15 (1.1%) were randomized controlled trials. The
      two principal themes were hepato-bilio-pancreatic surgery in 606 studies (44.8%)
      and colorectal surgery in 364 studies (26.9%). The overall rate of acceptance for
      the Congress was 49.9%, of which 21.0% were accepted for oral presentation. In
      multivariate analysis, the factors associated with acceptance for oral
      presentation were the geographic origin of the study (P<0.001), studies including
      >100 patients (P=0.01), and the prospective nature of the study (P=0.045). The
      rate of subsequent publication was 61.9% for studies accepted for oral
      presentation, 39.7% for studies accepted for poster presentation, and 25.9% for
      studies that were not accepted (P<0.001). In multivariate analysis, the factors
      associated with subsequent publication were geographic origin of the study
      (P=0.003), the experimental character of the study (P<0.001), and acceptance for
      presentation at the Congress (P<0.001). CONCLUSION: Only half of the studies
      submitted for presentation at the annual Congress of the SFCD/ACBHT are accepted;
      this nevertheless constitutes a quality measure associated with nearly a 50%
      chance of subsequent publication in the medical literature.

PMID- 24861941
TI  - Hydroxyethyl starch conjugates for improving the stability, pharmacokinetic
      behavior and antitumor activity of 10-hydroxy camptothecin.
AB  - 10-Hydroxy camptothecin (10-HCPT)-hydroxyethyl starch (HES) conjugates were
      prepared to improve the water solubility, prolong the half-life in plasma and
      increase the antitumor efficacy of 10-HCPT, and the structures of the conjugates
      were confirmed by NMR and infrared spectroscopy. The 10-HCPT conjugates showed
      good sustained release effect in phosphate-buffered saline (PBS), rat plasma and
      liver homogenate. Meanwhile, 10-HCPT-HES conjugates achieved much lower IC50 and
      higher cytotoxicity effects than the free 10-HCPT on Hep-3B and SMMC-7721 cell
      lines. The pharmacokinetics results of 10-HCPT-HES conjugates demonstrated that
      the biological half-life of 10-HCPT was increased from 10 min to 2.94 h and 3.76
      h, respectively, in comparison with the commercial 10-HCPT injection. The
      pharmacodynamics results indicated that 10-HCPT-HES conjugate had a better
      antitumor efficiency against nude mouse with Hep-3B tumor than the commercial 10
      HCPT injection, and the inhibition ratio of tumor was 78.3% and 31.5%,
      respectively, at the dose of 1.0 mg/kg. These findings suggest that 10-HCPT-HES
      conjugate is a promising drug delivery system providing improved long circulating
      effect, greater stability and better antitumor effect.

PMID- 24861939
TI  - A new approach to ELISA-based anti-glycolipid antibody evaluation of highly
      adhesive serum samples.
AB  - The enzyme-linked immunosorbent assay (ELISA) is a standard immunoassay used in
      measuring antibody reactivity (expressed as titers) for glycosphingolipids (GSLs)
      such as gangliosides and sulfoglycolipids in the sera of patients with Guillain
      Barre syndrome (GBS), variants of GBS, and chronic inflammatory demyelinating
      polyneuropathy (CIDP). In the present study, anti-GSL antibodies were evaluated
      using a new formula of affinity parametric complex (APC), calculated from
      limiting-dilution serum assay data, followed by affinity parametric complex
      criterion (APCC). Using assay results based on APCC, we analyzed serum samples
      categorized into acute inflammatory demyelinating polyneuropathy (AIDP), acute
      motor-sensory axonal neuropathy (AMSAN), CIDP, CIDP with myasthenia gravis (MG),
      and amyotrophic lateral sclerosis (ALS). We were able to determine the affinity
      strength of antibodies otherwise hidden in the non-specific background activity
      in highly adhesive serum samples. The thin-layer chromatography (TLC)-immuno
      overlay method assured us that this new method is an accurate and reliable way
      for evaluating anti-GSL antibodies using ELISA serum sample data.

PMID- 24861943
TI  - Infant Movement Motivation Questionnaire: development of a measure evaluating
      infant characteristics relating to motor development in the first year of life.
AB  - This paper highlights the development and testing of the Infant Movement
      Motivation Questionnaire (IMMQ), an instrument designed to evaluate qualities of
      infant characteristics that relate specifically to early motor development. The
      measurement development process included three phases: item generation, pilot
      testing and evaluation of acceptability and feasibility for parents and
      exploratory factor analysis. The resultant 27-item questionnaire is designed for
      completion by parents and contains four factors including Activity, Exploration,
      Motivation and Adaptability. Overall, the internal consistency of the IMMQ is
      0.89 (Cronbach's alpha), with test-retest reliability measured at 0.92 (ICC, with
      95% CI 0.83-0.96). Further work could be done to strengthen the individual
      factors; however it is adequate for use in its full form. The IMMQ can be used
      for clinical or research purposes, as well as an educational tool for parents.

PMID- 24861942
TI  - Preparation of immunostimulatory single-walled carbon nanotube/CpG DNA complexes
      and evaluation of their potential in cancer immunotherapy.
AB  - Carbon nanotubes (CNTs) have many interesting properties. In particular, their
      photohyperthermic effect by near-infrared (NIR) irradiation could be used to kill
      cancer cells, and could thus be applied in photohyperthermic therapy. However,
      the solubility of CNTs must be improved before they can be used in biological
      applications. As DNA is reported to disperse the CNTs in aqueous solution with pi
      pi interactions, we hypothesis that immunostimulatory CpG DNA may also disperse
      the CNTs in aqueous solution. In this study, we used CpG DNA to disperse single
      walled CNTs (SWCNTs) in aqueous solution, in order to combine photohyperthermic
      effect and immunoactivation together to achieve a more effective cancer therapy.
      As expected, CpG DNA effectively dispersed the SWCNTs in aqueous solution via the
      formation of SWCNT/CpG DNA complexes. Moreover, the immunoreactivity of the
      SWCNT/CpG DNA complexes was investigated. The results showed that intratumoral
      administration of the SWCNT/CpG DNA complexes in mice enhanced the production
      level of inflammatory cytokines in tumor tissues. Finally, we evaluated the
      antitumor effects of the SWCNT/CpG DNA complexes in tumor-bearing mice. The
      result indicated that intratumoral administration of the SWCNT/CpG DNA complexes
      combined with NIR irradiation was a more effective approach to prevent the
      proliferation of tumor growth. 

PMID- 24861944
TI  - Mitochondrial APE1/Ref-1 suppressed protein kinase C-induced mitochondrial
      dysfunction in mouse endothelial cells.
AB  - Protein kinase C (PKC) induces mitochondrial dysfunction, which is an important
      pathological factor in cardiovascular diseases. The role of apurinic/apyrimidinic
      endonuclease-1/redox factor-1 (APE1/Ref-1) on PKC-induced mitochondrial
      dysfunction has not been variously investigated. In this study, phorbol 12
      myristate 13-acetate (PMA), an activator of protein kinase C, induced
      mitochondrial hyperpolarization and reactive oxygen species generation and also
      increased mitochondrial translocation of APE1/Ref-1. APE1/Ref-1 overexpression
      suppressed PMA-induced mitochondrial dysfunction. In contrast, gene silencing of
      APE1/Ref-1 increased the sensitivity of mitochondrial dysfunction. Moreover,
      mitochondrial targeting sequence (MTS)-fused APE1/Ref-1 more effectively
      suppressed PMA-induced mitochondrial dysfunctions. These results suggest that
      mitochondrial APE1/Ref-1 is contributed to the protective role to protein kinase
      C-induced mitochondrial dysfunction in endothelial cells. 

PMID- 24861945
TI  - CXCL16 in kidney and cardiovascular injury.
AB  - CXC chemokine ligand 16 (CXCL16) is a CXC soluble chemokine, an adhesion molecule
      and a cell surface scavenger receptor. CXCL16 regulates inflammation, tissue
      injury and fibrosis. Parenchymal renal cells, vascular wall cells, leukocytes and
      platelets express and/or release CXCL16 under the regulation of inflammatory
      mediators. CXCL16 expression is increased in experimental and human
      nephropathies. Targeting CXCL16 protected from experimental glomerular injury or
      interstitial fibrosis. Conflicting results were reported for experimental
      cardiovascular injury. High circulating CXCL16 levels are associated to human
      kidney and cardiovascular disease and urinary CXCL16 may increase in kidney
      injury. In conclusion, mounting evidence suggests a role of CXCL16 in kidney and
      cardiovascular disease. However, a better understanding is still required before
      exploring CXCL16 targeting in the clinic. 

PMID- 24861946
TI  - PML control of cytokine signaling.
AB  - The promyelocytic leukemia (PML) protein is a tumor suppressor acting as the
      organizer of nuclear matrix-associated structures named nuclear bodies (NBs). The
      involvement of PML in various cell processes, including cell death, senescence or
      antiviral defense underlines the multiple functions of PML due to its ability to
      interact with various partners either in the cytoplasm or in the nucleus. The
      importance of paracrine signaling in the regulation of PML expression is well
      established. More recently, a growing body of evidence also supports PML as a key
      regulator of cytokine signaling. These findings shed light on unsuspected
      biological functions of PML such as immune response, inflammation and cytokine
      induced apoptosis. Here we review the current understanding of the pleiotropic
      activities of PML on cytokine-induced signaling.

PMID- 24861947
TI  - Who climbs the tryptophan ladder? On the structure and function of the WSXWS
      motif in cytokine receptors and thrombospondin repeats.
AB  - For decades, a spectacular structural motif has been the focus of research in two
      families of animal membrane proteins: the hematopoietic cytokine type I receptors
      (HCR) and the thrombospondin repeat type 1 (TSR-1) domain containing proteins.
      Although these families include some of the best-studied and pharmaceutically
      most interesting human proteins, the function of the motif remains elusive. Here
      we show that the molecular details of the motifs are the same; that it has arisen
      through convergent evolution, and we argue that the same ligand binding function
      is maintained and suggest that the ligand can be found in the extracellular
      matrix (ECM). We term the motif the tryptophan ladder and suggest a function
      based on a comparative analysis. 

PMID- 24861949
TI  - Inflammatory cytokines and VEGF measured in exhaled breath condensate are
      correlated with tumor mass in non-small cell lung cancer.
AB  - Inflammation mediated by the immune system is known to be important in
      carcinogenesis and, specifically, T helper 17 cells have been reported to play a
      role in tumor progression by promoting neo-angiogenesis. The aim of this study
      was to investigate whether inflammatory cytokines and vascular endothelial growth
      factor (VEGF) levels in exhaled breath condensate (EBC) and in serum were related
      to tumor size in patients with non-small cell lung cancer (NSCLC). Il-6, IL-17,
      TNF-alpha and VEGF levels were measured in EBC and serum of 15 patients with
      stage I-IIA NSCLC and in 30 healthy controls by immunoassay. The tumor size was
      measured by a CT scan. The concentrations of IL-6, IL-17 and VEGF were
      significantly higher in EBC of patients with lung cancer, compared with controls,
      while only serum IL-6 concentration was higher in patients compared to controls.
      A significant correlation (r = 0.78, p = 0.001) was observed between EBC levels
      of IL-6 and IL-17; IL-17 was also correlated to EBC levels of the VEGF (r = 0.83,
      p < 0.001) and TNF-alpha (r = 0.62, p = 0.014). The tumor diameter was
      significantly correlated with EBC concentrations of VEGF (r = 0.58, p = 0.039),
      IL-6 (r = 0.67, p = 0.013) and IL-17 (r = 0.66, p = 0.017). Our results show a
      significant relationship between inflammatory and angiogenic markers, measured in
      EBC by a non-invasive method, and tumor mass. 

PMID- 24861950
TI  - Employment among schoolchildren and its associations with adult substance use,
      psychological well-being, and academic achievement.
AB  - PURPOSE: To examine the association between paid part-time employment among
      schoolchildren, and adult substance use, psychological well-being, and academic
      achievement. METHODS: Longitudinal data from the Dunedin Multidisciplinary Health
      and Development Study were used to evaluate the association between employment at
      each of 11, 13, and 15 years and adult smoking, regular alcohol binge drinking,
      regular cannabis use, sense of coherence, social participation, positive coping
      style, prosociality, no formal qualifications, and university degree.
      Associations were initially assessed using unadjusted regression analyses and
      then adjusted for the potential childhood confounders intelligence quotient,
      reading development, Student's Perception of Ability Scale, socioeconomic
      disadvantage, family climate, harsh parent-child interaction, parental opinion of
      their child's attitude to school, and child's personal attitude to school.
      RESULTS: Employment at 11 years of age was associated with a lower odds of adult
      smoking; the odds of subsequent regular alcohol binge drinking were greater for
      those who were employed at age 13; and higher adult rates of social participation
      and prosociality were identified for adolescents who were employed at 15 years of
      age. When the potential confounders were controlled, employment at age 13 was
      predictive of both adult smoking and regular binge drinking, and working at 15
      years of age was protective against regular cannabis use and associated with
      greater social participation. CONCLUSIONS: There is no consistent evidence that
      exposing schoolchildren to part-time employment compromised subsequent health,
      well-being, and education in a developed country.

PMID- 24861952
TI  - Racial disparities in prostate cancer-specific mortality in men with low-risk
      prostate cancer.
AB  - BACKGROUND: Men with low-risk prostate cancer (CaP) are considered unlikely to
      die of CaP and have the option of active surveillance. This study evaluated
      whether African American (AA) men who present with low-risk disease are at higher
      risk for death from CaP than white men. PATIENTS AND METHODS: The authors
      identified 56,045 men with low-risk CaP (T1-T2a, Gleason score <= 6, prostate
      specific antigen <= 10 ng/mL) diagnosed between 2004 and 2009 using the
      Surveillance, Epidemiology, and End Results (SEER) database. Fine-Gray competing
      risks regression analyses were used to analyze the effect of race on prostate
      cancer-specific mortality (PCSM) after adjusting for known prognostic and
      sociodemographic factors in 51,315 men (43,792 white; 7523 AA) with clinical
      follow-up information available. RESULTS: After a median follow-up of 46 months,
      258 patients (209 [0.48%] white and 49 [0.65%] AA men) died from CaP. Both AA
      race (adjusted hazard ratio [AHR], 1.45; 95% CI, 1.03-2.05; P = .032) and
      noncurative management (AHR, 1.49; 95% CI, 1.15-1.95; P = .003) were
      significantly associated with an increased risk of PCSM. When analyzing only
      patients who underwent curative treatment, AA race (AHR, 1.62; 95% CI, 1.04-2.53;
      P = .034) remained significantly associated with increased PCSM. CONCLUSION:
      Among men with low-risk prostate cancer, AA race compared with white race was
      associated with a higher risk of PCSM, raising the possibility that clinicians
      may need to exercise caution when recommending active surveillance for AA men
      with low-risk disease. Further studies are needed to ultimately determine whether
      guidelines for active surveillance should take race into account.

PMID- 24861951
TI  - Sarcomatoid dedifferentiation in metastatic clear cell renal cell carcinoma and
      outcome on treatment with anti-vascular endothelial growth factor receptor
      tyrosine kinase inhibitors: a retrospective analysis.
AB  - INTRODUCTION: This study aimed to assess the efficacy of anti-vascular
      endothelial growth factor receptor tyrosine kinase inhibitors (anti-VEGFR-TKIs)
      in patients with metastatic clear cell renal cell carcinoma (m-ccRCC) with
      sarcomatoid dedifferentiation. PATIENTS AND METHODS: The files of all patients
      with m-ccRCC consecutively treated with first-line anti-VEGFR-TKIs at the
      authors' institution were retrospectively reviewed. Pathology slides from
      nephrectomy and metastasectomy were assessed for the presence and extent of
      sarcomatoid dedifferentiation. RESULTS: A total of 124 patients were included;
      nephrectomy and metastasectomy specimens were available in 117 and 35 patients,
      respectively. Thirty percent of the primary nephrectomy specimens had sarcomatoid
      features, and the median involvement of the sarcomatoid component was 21% (range,
      1%-95%). Patients with an important sarcomatoid component, defined as >= 25%
      involvement of the tumor, had a very poor outcome: progression-free survival
      (PFS) and overall survival (OS) were 3 and 6 months, respectively, and no partial
      responses (PR) were observed. Patients without sarcomatoid dedifferentiation or
      with sarcomatoid involvement < 25% had a PFS of 12 months (P < .0001; hazard
      ratio [HR], 51; 95% CI, 12.58-207.3), an OS of 22 months (P < .0001, HR, 10.72;
      95% CI, 3.56-32.25), and a PR rate of 50% (P = .0015). Patients with a
      sarcomatoid component >= 25% in the metastasectomy also had a poorer PFS and OS
      on anti-VEGFR-TKIs compared with patients with < 25% of sarcomatoid features at
      these sites. CONCLUSION: Patients with m-ccRCC whose tumors contain a component
      of sarcomatoid dedifferentiation of >= 25% of the total tumor volume have a very
      poor outcome when treated with anti-VEGFR-TKIs. Analysis of the extent of
      sarcomatoid features in resected metastases can provide additional prognostic
      information.

PMID- 24861954
TI  - Hydrogenation of biofuels with formic acid over a palladium-based ternary
      catalyst with two types of active sites.
AB  - A composite catalyst including palladium nanoparticles on titania (TiO2) and on
      nitrogen-modified porous carbon (Pd/TiO2@N-C) is synthesized from palladium
      salts, tetrabutyl titanate, and chitosan. N2 sorption isotherms show that the
      catalyst has a high BET surface area (229 m(2)  g(-1)) and large porosity. XPS
      and TEM characterization of the catalyst shows that palladium species with
      different chemical states are well dispersed across the TiO2 and nitrogen
      modified porous carbon, respectively. The Pd/TiO2@N-C catalyst is very active and
      shows excellent stability towards hydrogenation of vanillin to 2-methoxy-4
      methylphenol using formic acid as hydrogen source. This activity can be
      attributed to a synergistic effect between the Pd/TiO2 (a catalyst for
      dehydrogenation of formic acid) and Pd/N-C (a catalyst for hydrogenation of
      vanillin) sites.

PMID- 24861955
TI  - Phosphine- and hydrogen-free: highly regioselective ruthenium-catalyzed
      hydroaminomethylation of olefins.
AB  - A highly regioselective ruthenium-catalyzed hydroaminomethylation of olefins is
      reported. Using easily available trirutheniumdodecacarbonyl an efficient sequence
      consisting of a water-gas shift reaction, hydroformylation of olefins, with
      subsequent imine or enamine formation and final reduction is realized. This novel
      procedure is highly practical (ligand-free, one pot) and economic (low catalyst
      loading and inexpensive metal). Bulk industrial as well as functionalized olefins
      react with various amines to give the corresponding tertiary amines generally in
      high yields (up to 92 %), excellent regioselectivities (n/iso>99:1), and full
      chemoselectivity in favor of terminal olefins. 

PMID- 24861953
TI  - Sub-15-nm patterning of asymmetric metal electrodes and devices by adhesion
      lithography.
AB  - Coplanar electrodes formed from asymmetric metals separated on the nanometre
      length scale are essential elements of nanoscale photonic and electronic devices.
      Existing fabrication methods typically involve electron-beam lithography--a
      technique that enables high fidelity patterning but suffers from significant
      limitations in terms of low throughput, poor scalability to large areas and
      restrictive choice of substrate and electrode materials. Here, we describe a
      versatile method for the rapid fabrication of asymmetric nanogap electrodes that
      exploits the ability of selected self-assembled monolayers to attach conformally
      to a prepatterned metal layer and thereby weaken adhesion to a subsequently
      deposited metal film. The method may be carried out under ambient conditions
      using simple equipment and a minimum of processing steps, enabling the rapid
      fabrication of nanogap electrodes and optoelectronic devices with aspect ratios
      in excess of 100,000.

PMID- 24861956
TI  - Integration of an inorganic semiconductor with a metal-organic framework: a
      platform for enhanced gaseous photocatalytic reactions.
AB  - Ultrafast spectroscopy demonstrates that charge transfer can occur between
      photoexcited inorganic semiconductors and metal-organic frameworks (MOFs),
      supplying long-lifetime electrons for the reduction of gas molecules adsorbed on
      the MOF. As a proof of concept, a unique method is developed for synthesizing Cu3
      (BTC)2 @TiO2 core-shell structures with macroporous semiconductor shells that
      allow gas molecules to be captured in the cores. 

PMID- 24861948
TI  - The first 1000 cultured species of the human gastrointestinal microbiota.
AB  - The microorganisms that inhabit the human gastrointestinal tract comprise a
      complex ecosystem with functions that significantly contribute to our systemic
      metabolism and have an impact on health and disease. In line with its importance,
      the human gastrointestinal microbiota has been extensively studied. Despite the
      fact that a significant part of the intestinal microorganisms has not yet been
      cultured, presently over 1000 different microbial species that can reside in the
      human gastrointestinal tract have been identified. This review provides a
      systematic overview and detailed references of the total of 1057 intestinal
      species of Eukarya (92), Archaea (8) and Bacteria (957), based on the
      phylogenetic framework of their small subunit ribosomal RNA gene sequences.
      Moreover, it unifies knowledge about the prevalence, abundance, stability,
      physiology, genetics and the association with human health of these
      gastrointestinal microorganisms, which is currently scattered over a vast amount
      of literature published in the last 150 years. This detailed physiological and
      genetic information is expected to be instrumental in advancing our knowledge of
      the gastrointestinal microbiota. Moreover, it opens avenues for future
      comparative and functional metagenomic and other high-throughput approaches that
      need a systematic and physiological basis to have an impact. 

PMID- 24861958
TI  - Nuclear magnetic resonance spectroscopy for determining the functional content of
      organic aerosols: a review.
AB  - The knowledge deficit of organic aerosol (OA) composition has been identified as
      the most important factor limiting our understanding of the atmospheric fate and
      implications of aerosol. The efforts to chemically characterize OA include the
      increasing utilization of nuclear magnetic resonance spectroscopy (NMR). Since
      1998, the functional composition of different types, sizes and fractions of OA
      has been studied with one-dimensional, two-dimensional and solid state proton and
      carbon-13 NMR. This led to the use of functional group ratios to reconcile the
      most important sources of OA, including secondary organic aerosol and initial
      source apportionment using positive matrix factorization. Future research efforts
      may be directed towards the optimization of experimental parameters, detailed NMR
      experiments and analysis by pattern recognition methods to identify the chemical
      components, determination of the NMR fingerprints of OA sources and solid state
      NMR to study the content of OA as a whole. 

PMID- 24861957
TI  - Chromatin maintenance and dynamics in senescence: a spotlight on SAHF formation
      and the epigenome of senescent cells.
AB  - Senescence is a stable proliferation arrest characterized by profound changes in
      cellular morphology and metabolism as well as by extensive chromatin
      reorganization in the nucleus. One particular hallmark of chromatin changes
      during senescence is the formation of punctate DNA foci in DAPI-stained senescent
      cells that have been called senescence-associated heterochromatin foci (SAHF).
      While many advances have been made concerning our understanding of the effectors
      of senescence, how chromatin is reorganized and maintained in senescent cells has
      remained largely elusive. Because chromatin structure is inherently dynamic,
      senescent cells face the challenge of developing chromatin maintenance mechanisms
      in the absence of DNA replication in order to maintain the senescent phenotype.
      Here, we summarize and review recent findings shedding light on SAHF composition
      and formation via spatial repositioning of chromatin, with a specific focus on
      the role of lamin B1 for this process. In addition, we discuss the physiological
      implication of SAHF formation, the role of histone variants, and histone
      chaperones during senescence and also elaborate on the more general changes
      observed in the epigenome of the senescent cells. 

PMID- 24861960
TI  - First-time, isolated surgical aortic valve replacement after prior coronary
      artery bypass surgery: results from the RECORD multicenter registry.
AB  - BACKGROUND: This multicenter study was undertaken to determine the immediate and
      long-term outcomes in patients undergoing a primary surgical aortic valve
      replacement (AVR) who had a previous coronary artery bypass graft surgery with
      patent grafts. METHODS: One hundred and thirteen consecutive patients (mean
      EuroSCORE II, 10.3 +/- 7.7%, median 8.0%) who underwent first-time isolated AVR
      after coronary artery bypass grafting (CABG) were the subjects of this
      multicenter study. The procedure was performed through a full sternotomy in 95.7%
      of cases, a patent internal mammary artery graft was clamped in 76.6% of
      patients. The temperature of cardioplegia was <=12  degrees C in 62.8% of
      patients and systemic temperature was <32  degrees C in 23.9% of patients.
      RESULTS: Thirty-day mortality was 4.4%. Stroke was observed in 8.0% of patients,
      low cardiac output syndrome in 14.1%, prolonged tracheal intubation in 20.8%, and
      intensive care unit stay was longer than five days in 19.5% of patients. Among
      patients with a patent internal mammary graft (91 patients), clamping of this
      graft (5.7% vs. 0%, p = 0.57) was associated with a nonsignificant trend toward
      increased 30-day mortality. One-, three- and five-year survival rates were 91.5%,
      90.4%, and 88.4%, respectively. CONCLUSIONS: Patients undergoing isolated AVR
      after prior CABG have a good immediate and late survival. A history of prior CABG
      should not be considered an absolute indication for transcatheter AVR.

PMID- 24861961
TI  - Atomic dynamic functional interaction patterns for characterization of ADHD.
AB  - Modeling abnormal temporal dynamics of functional interactions in psychiatric
      disorders has been of great interest in the neuroimaging field, and thus a
      variety of methods have been proposed so far. However, the temporal dynamics and
      disease-related abnormalities of functional interactions within specific data
      driven discovered subnetworks have been rarely explored yet. In this work, we
      propose a novel computational framework composed of an effective Bayesian
      connectivity change point model for modeling functional brain interactions and
      their dynamics simultaneously and an effective variant of nonnegative matrix
      factorization for assessing the functional interaction abnormalities within
      subnetworks. This framework has been applied on the resting state fmagnetic
      resonance imaging (fMRI) datasets of 23 children with attention
      deficit/hyperactivity disorder (ADHD) and 45 normal control (NC) children, and
      has revealed two atomic functional interaction patterns (AFIPs) discovered for
      ADHD and another two AFIPs derived for NC. Together, these four AFIPs could be
      grouped into two pairs, one common pair representing the common AFIPs in ADHD and
      NC, and the other abnormal pair representing the abnormal AFIPs in ADHD.
      Interestingly, by comparing the abnormal AFIP pair, two data-driven abnormal
      functional subnetworks are derived. Strikingly, by evaluating the approximation
      based on the four AFIPs, all of the ADHD children were successfully
      differentiated from NCs without any false positive.

PMID- 24861959
TI  - A comparison of live counseling with a web-based lifestyle and medication
      intervention to reduce coronary heart disease risk: a randomized clinical trial.
AB  - IMPORTANCE: Most primary care clinicians lack the skills and resources to offer
      effective lifestyle and medication (L&M) counseling to reduce coronary heart
      disease (CHD) risk. Thus, effective and feasible CHD prevention programs are
      needed for typical practice settings. OBJECTIVE: To assess the effectiveness,
      acceptability, and cost-effectiveness of a combined L&M intervention to reduce
      CHD risk offered in counselor-delivered and web-based formats. DESIGN, SETTING,
      AND PARTICIPANTS: A comparative effectiveness trial in 5 diverse family medicine
      practices in North Carolina. Participants were established patients, aged 35 to
      79 years, with no known cardiovascular disease, and at moderate to high risk for
      CHD (10-year Framingham Risk Score [FRS], >=10%). INTERVENTIONS: Participants
      were randomized to counselor-delivered or web-based format, each including 4
      intensive and 3 maintenance sessions. After randomization, both formats used a
      web-based decision aid showing potential CHD risk reduction associated with L&M
      risk-reducing strategies. Participants chose the risk-reducing strategies they
      wished to follow. MAIN OUTCOMES AND MEASURES: The primary outcome was within
      group change in FRS at 4-month follow-up. Other measures included standardized
      assessments of blood pressure, blood lipid levels, lifestyle behaviors, and
      medication adherence. Acceptability and cost-effectiveness were also assessed.
      Outcomes were assessed at 4 and 12 months. RESULTS: Of 2274 screened patients,
      385 were randomized (192 counselor; 193 web): mean age, 62 years; 24% African
      American; and mean FRS, 16.9%. Follow-up at 4 and 12 months included 91% and 87%
      of the randomized participants, respectively. There was a sustained reduction in
      FRS at both 4 months (primary outcome) and 12 months for both counselor-based (
      2.3% [95% CI, -3.0% to -1.6%] and -1.9% [95% CI, -2.8% to -1.1%], respectively)
      and web-based groups (-1.5% [95% CI, -2.2% to -0.9%] and -1.7% [95% CI, -2.6% to 
      0.8%] respectively). At 4 months, the adjusted difference in FRS between groups
      was -1.0% (95% CI, -1.8% to -0.1%) (P = .03), and at 12 months, it was -0.6% (95%
      CI, -1.7% to 0.5%) (P = .30). The 12-month costs from the payer perspective were
      $207 and $110 per person for the counselor- and web-based interventions,
      respectively. CONCLUSIONS AND RELEVANCE: Both intervention formats reduced CHD
      risk through 12-month follow-up. The web format was less expensive. TRIAL
      REGISTRATION: clinicaltrials.gov Identifier: NCT01245686.

PMID- 24861963
TI  - Abstracts of the The Society for Cardiovascular Angiography and Interventions'
      37th Annual Scientific Sessions, May 28-31, 2014, Las Vegas, Nevada.

PMID- 24861962
TI  - Maternal and child health nurses' self-perceived confidence in dealing with child
      behaviour problems.
AB  - BACKGROUND: Addressing behaviour problems in children is increasingly becoming
      part of routine care. The question therefore arises as to which workforce members
      are best suited to deliver structured interventions and what skill sets they
      might need apart from knowledge of the specific parenting programme offered.
      OBJECTIVES: To assess maternal and child health (MCH) nurses' self-perceived
      confidence in dealing with child behaviour problems. DESIGN: Cross-sectional
      questionnaire study. Data collection occurred prior to cluster randomization in
      the Families in Mind trial. SETTING: MCH clinics in nine local government areas
      in greater Melbourne, in 2010. PARTICIPANTS: All MCH nurses in the nine areas
      were invited to participate, 153 (79%) completed the survey. MAIN OUTCOMES
      MEASURES: Nurses' comfort, competency, attitudes and perceived difficulties in
      dealing with child behaviour problems. RESULTS: The majority of nurses (63%)
      viewed it as their role to deal with, rather than refer, child behaviour problems
      and felt that the task was rewarding (86%). They believed that parenting advice
      should be offered universally, rather than only to families with severe problems
      (94%). Nurses felt rather comfortable and competent to broach and discuss child
      behaviour problems without need for prior parental request, but somewhat less
      comfortable and competent to manage child behaviour problems or to make a
      difference. Experienced nurses (>10 years in practice) felt more comfortable and
      competent. Nurses described that the major challenge in their dealing with child
      behaviour problems was parental denial or resistance (60%). CONCLUSIONS: MCH
      nurses are at the frontline of preventive medical services for families with
      young children where behaviour problems are a common concern. Because managing
      young children's behaviour problems primarily occurs through adult behaviour
      change, techniques addressing parent denial and non-compliance, such as
      motivational interviewing and empowerment should be a part of MCH nurses' skill
      sets.

PMID- 24861964
TI  - What is the current status of chondroitin sulfate and glucosamine for the
      treatment of knee osteoarthritis?
AB  - Chondroitin sulfate and glucosamine sulfate exert beneficial effects on the
      metabolism of in vitro models of cells derived from synovial joints:
      chondrocytes, synoviocytes and cells from subchondral bone, all of which are
      involved in osteoarthritis (OA). They increase type II collagen and proteoglycan
      synthesis in human articular chondrocytes and are able to reduce the production
      of some pro-inflammatory mediators and proteases, to reduce the cellular death
      process, and improve the anabolic/catabolic balance of the extracellular
      cartilage matrix (ECM). Clinical trials have reported a beneficial effect of
      chondroitin sulfate and glucosamine sulfate on pain and function. The structure
      modifying effects of these compounds have been reported and analyzed in recent
      meta-analyses. The results for knee OA demonstrate a small but significant
      reduction in the rate of joint space narrowing. Chondroitin sulfate and
      glucosamine sulphate are recommended by several guidelines from international
      societies for the management of knee and hip OA, while others do not recommend
      these products or recommend only under condition. This comprehensive review
      clarifies the role of these compounds in the therapeutic arsenal for patients
      with knee OA. 

PMID- 24861965
TI  - Cervical cancer in the older woman.
AB  - OBJECTIVES: (1) To understand whether women who are older when diagnosed with
      cervical cancer have a poorer survival compared to those younger, and if so, to
      determine the relative importance of patient, tumor and treatment factors. (2) To
      review whether older women are candidates for aggressive curative treatment for
      their cervical cancer and the age related effectiveness and toxicity. METHODS: A
      review of the published English literature from 1990 to 2014 using search terms
      related to cervical cancer and older age was conducted. RESULTS: A number of
      confounders may influence whether advanced age impacts survival such as patient
      comorbidities, stage, histology, grade, no or incomplete treatment, less radical
      surgery, palliative rather than curative treatment, lack of adjuvant radiation
      after surgery, lower rates of chemotherapy and others. When older women are
      treated as aggressively as their younger counterparts, survival is the same;
      however, especially where radiation or chemotherapy is used, toxicities may occur
      at the same or slightly higher rate. CONCLUSIONS: The more recent population
      based studies have larger sample sizes and minimize the biases seen in single
      center studies. They have also corrected for confounders giving a more accurate
      answer concerning the outcomes of older women treated for cervical cancer.
      Performance status (or "frailty") and not chronologic age should define the
      optimal treatment strategy for older women with cervical cancer. Treatment
      related toxicities can be managed with treatment breaks or dose reductions. For
      those who receive curative treatment, the outcomes appear similar regardless of
      age.

PMID- 24861966
TI  - Liposome supported metal oxide nanoparticles: interaction mechanism, light
      controlled content release, and intracellular delivery.
AB  - Zwitterionic phosphotydylcholine lipo-somes stably adsorb a number of metal oxide
      nanoparticles via its phosphate group. This is different from physisorption and
      fusion with SiO2. The hybrid materials can be internalized by cancer cells and
      TiO2 allows light controlled liposome content release.

PMID- 24861967
TI  - Speciation and detection of arsenic in aqueous samples: a review of recent
      progress in non-atomic spectrometric methods.
AB  - Inorganic arsenic (As) displays extreme toxicity and is a class A human
      carcinogen. It is of interest to both analytical chemists and environmental
      scientists. Facile and sensitive determination of As and knowledge of the
      speciation of forms of As in aqueous samples are vitally important. Nearly every
      nation has relevant official regulations on permissible limits of drinking water
      As content. The size of the literature on As is therefore formidable. The heart
      of this review consists of two tables: one is a compilation of principal official
      documents and major review articles, including the toxicology and chemistry of
      As. This includes comprehensive official compendia on As speciation, sample
      treatment, recommended procedures for the determination of As in specific sample
      matrices with specific analytical instrument(s), procedures for multi-element
      (including As) speciation and analysis, and prior comprehensive reviews on
      arsenic analysis. The second table focuses on the recent literature (2005-2013,
      the coverage for 2013 is incomplete) on As measurement in aqueous matrices.
      Recent As speciation and analysis methods based on spectrometric and
      electrochemical methods, inductively coupled plasma-mass spectrometry, neutron
      activation analysis and biosensors are summarized. We have deliberately excluded
      atomic optical spectrometric techniques (atomic absorption, atomic fluorescence,
      inductively coupled plasma-optical emission spectrometry) not because they are
      not important (in fact the majority of arsenic determinations are possibly
      carried out by one of these techniques) but because these methods are
      sufficiently mature and little meaningful innovation has been made beyond what is
      in the officially prescribed compendia (which are included) and recent reviews
      are available. 

PMID- 24861968
TI  - Bismuth as a general internal standard for lead in atomic absorption
      spectrometry.
AB  - Bismuth was evaluated as internal standard for Pb determination by line source
      flame atomic absorption spectrometry (LS FAAS), high-resolution continuum source
      flame atomic absorption spectrometry (HR-CS FAAS) and line source graphite
      furnace atomic absorption spectrometry (LS GFAAS). Analysis of samples containing
      different matrices indicated close relationship between Pb and Bi absorbances.
      Correlation coefficients of calibration curves built up by plotting
      A(Pb)/A(Bi)versus Pb concentration were higher than 0.9953 (FAAS) and higher than
      0.9993 (GFAAS). Recoveries of Pb improved from 52-118% (without IS) to 97-109%
      (IS, LS FAAS); 74-231% (without IS) to 96-109% (IS, HR-CS FAAS); and 36-125%
      (without IS) to 96-110% (IS, LS GFAAS). The relative standard deviations (n=12)
      were reduced from 0.6-9.2% (without IS) to 0.3-4.3% (IS, LS FAAS); 0.7-7.7%
      (without IS) to 0.1-4.0% (IS, HR-CS FAAS); and 2.1-13% (without IS) to 0.4-5.9%
      (IS, LS GFAAS). 

PMID- 24861969
TI  - Localization of proteins in paint cross-sections by scanning electrochemical
      microscopy as an alternative immunochemical detection technique.
AB  - The qualitative identification of proteinaceous substances, as well as their
      location within a complex paint stratigraphy, is one of the most challenging
      issues in the characterization of painting materials. Nevertheless, information
      on paint components represent a crucial task for studies concerning both the
      ancient painting techniques adopted and the state of conservation, being
      fundamental investigations for the selection of appropriate conservation actions.
      The present research was aimed at developing a new detection approach for the
      immunochemical localization of ovalbumin in paint cross-sections based on the use
      of scanning electrochemical microscopy (SECM). The immunochemical analyses were
      performed using an anti-ovalbumin primary antibody and a secondary antibody
      labelled with horseradish peroxidase (HRP). SECM measurements were performed in
      feedback mode using benzoquinone (BQ)/hydroquinone (H2Q) redox couple. In
      presence of hydrogen peroxide (H2O2), HRP catalyzes the re-oxidation of H2Q to BQ
      and the increment of BQ concentration in correspondence of the target protein was
      detected by SECM through the electrochemical reduction of the regenerated BQ at
      the microelectrode. Indeed, the localization of ovalbumin was possible thanks to
      a clear discrimination of SECM currents, achieved by the comparison of the
      measurements recorded before and after H2O2 administration, based on the HRP
      on/off approach. The method was evaluated both on samples from standard mocks-up
      and on a historical sample, collected from a Renaissance wood painting. The
      obtained results were promising, foreseeing a wider application of SECM on
      cultural heritage researches. 

PMID- 24861970
TI  - Electrochemical recognition and trace-level detection of bactericide carbendazim
      using carboxylic group functionalized poly(3,4-ethylenedioxythiophene) mimic
      electrode.
AB  - The electrochemical recognition and trace-level detection of bactericide
      carbendazim (MBC) in paddy water and commercial juice were realized using
      carboxylic group functionalized poly(3,4-ethylenedioxythiophene) (PC4-EDOT-COOH)
      film electrode. PC4-EDOT-COOH film was prepared by one step, low-cost, and green
      electrosynthesis in aqueous microemulsion system and characterized by FT-IR,
      cyclic voltammetry, UV-vis and SEM. In comparison with poly(3,4
      ethylenedioxythiophene) (PEDOT) and poly(hydroxymethylated-3,4
      ethylenedioxylthiophene) (PEDTM), PC4-EDOT-COOH exhibited the best
      electrochemical recognition towards MBC and the recognition mechanism was proved
      by quantitative calculation. Sensing parameters such as pH values, accumulation
      potential, accumulation time, supporting electrolyte, and scan rate on the
      current response of MBC were discussed. In addition, the sensor can be applied to
      quantification of MBC in the concentration range of 0.012-0.35 MUM with a low
      detection limit of 3.5 nM (S/N=3). Moreover, PC4-EDOT-COOH film electrode showed
      good stability, high selectivity, and satisfactory anti-interference ability.
      Satisfactory results indicated that PC4-EDOT-COOH film is a promising sensing
      platform for the trace-level analysis of bactericide residue carbendazim in
      agricultural crops and environment.

PMID- 24861971
TI  - Preparation of NiFe2O4/graphene nanocomposite and its application as a modifier
      for the fabrication of an electrochemical sensor for the simultaneous
      determination of tramadol and acetaminophen.
AB  - An effective electrochemical sensor for the rapid and simultaneous determination
      of tramadol and acetaminophen based on carbon paste electrode (CPE) modified with
      NiFe2O4/graphene nanoparticles was developed. The structures of the synthesized
      NiFe2O4/graphene nanocomposite and the electrode composition were confirmed by X
      ray diffraction (XRD) spectrometry, Fourier transform infrared (FT-IR)
      spectrometry and scanning electron microscopy (SEM). The peak currents of square
      wave voltammetry of tramadol and acetaminophen increased linearly with their
      concentration in the range of 0.01-9 MUmol L(-1). The detection limit for their
      determination was found to be 0.0036 and 0.0030 MUmol L(-1), respectively. The
      results show that the combination of graphene and NiFe2O4 nanoparticles causes a
      dramatic enhancement in the sensitivity of the sensor. The fabricated sensor
      exhibited high sensitivity and good stability, and would be valuable for the
      clinical assay of tramadol and acetaminophen.

PMID- 24861972
TI  - Ultrasensitive detection of lead ion based on target induced assembly of DNAzyme
      modified gold nanoparticle and graphene oxide.
AB  - In this paper, we report a novel colorimetric strategy for the detection of small
      molecules by using Pb(2+) ion as an example. In this strategy, DNAzyme duplex
      modified gold nanoparticles (GNPs) are designed to be unable to interact with
      graphene oxide (GO). However, in the presence of Pb(2+), the substrate strand of
      the DNAzyme is cleaved at its cleavage site, resulting in the disassembly of the
      DNAzyme duplex modified GNPs into three parts, i.e., the 3'- and 5'-fragments of
      substrate strand and the DNAzyme strand modified GNPs. By taking advantage of the
      efficient cross-linking effect of ssDNA-GNPs to GO, colorimetric sensor for the
      detection of the metal ion can be fabricated with a detection limit of 100 pM,
      which is much lower than the previous reports. This colorimetric method has also
      been used for the determination of Pb(2+) in the tap water of the local city and
      the water from a reservoir with satisfactory results, so it may have potential
      applications in the future.

PMID- 24861973
TI  - Does every US smoker bear the same cigarette tax?
AB  - AIMS: To evaluate state cigarette excise tax pass-through rates for selected
      price-minimizing strategies. DESIGN: Multivariate regression analysis of current
      smokers from a stratified, national, dual-frame telephone survey. SETTING: United
      States. PARTICIPANTS: A total of 16 542 adult current smokers aged 18 years or
      older. MEASUREMENTS: Cigarette per pack prices paid with and without coupons were
      obtained for pack versus carton purchase, use of generic brands versus premium
      brands, and purchase from Indian reservations versus outside Indian reservations.
      FINDINGS: The average per pack prices paid differed substantially by price
      minimizing strategy. Smokers who used any type of price-minimizing strategies
      paid substantially less than those who did not use these strategies (P < 0.05).
      Premium brand users who purchased by pack in places outside Indian reservations
      paid the entire amount of the excise tax, together with an additional premium of
      7-10 cents per pack for every $1 increase in excise tax (pass-through rate of
      1.07-1.10, P < 0.05). In contrast, carton purchasers, generic brand users or
      those who were likely to make their purchases on Indian reservations paid only 30
      83 cents per pack for every $1 tax increase (pass-through rate of 0.30-0.83, P <
      0.05). CONCLUSIONS: Many smokers in the United States are able to avoid the full
      impact of state excise tax on cost of smoking by buying cartons, using generic
      brands and buying from Indian reservations.

PMID- 24861974
TI  - Assessing the feasibility of using uniaxial accelerometers with an online support
      platform in the delivery of a community-based exercise referral scheme.
AB  - Exercise referral schemes are established within community-based health care;
      however, they have been criticized for failing to evidence long-term behavior
      change relative to usual care. As such, recent reviews have called for refinement
      of their delivery with a focus on embedded strategies targeting client
      motivation. This research letter presents findings from an initial pilot trial
      conducted within Wales' National Exercise Referral Scheme (NERS), examining the
      feasibility of using validated physical activity monitoring devices and an
      accompanying online platform within standard scheme delivery. 30 individuals
      referred to generic or cardiovascular pathways were offered the system; of these
      17 agreed to participate. Common reasons for declining were clustered into lack
      of technology literacy or access, condition severity, or fear of costs associated
      with losing the device. Analysis of follow-up interviews after 4 weeks of use
      indicated that while participants found the monitoring devices practical and
      informative, only a minority (n = 4) were using the system in full. Crucially,
      the system element most aligned with contemporary theories of motivation (the
      online portal) was not used as expected. In addition, feedback from exercise
      referral professionals indicated that there were demands for support from
      clients, which might be mitigated by more effective independent system use.
      Recommendations for larger scale trials using similar systems include
      consideration of targeted patient groups, equity of access, and providing
      adequate technological support that is currently beyond the capacity of the NERS
      system. 

PMID- 24861976
TI  - Aberrantly Over-Expressed TRPM8 Channels in Pancreatic Adenocarcinoma:
      Correlation with Tumor Size/Stage and Requirement for Cancer Cells Invasion.
AB  - The transient receptor potential melastatin-subfamily member 8 (TRPM8) channels
      control Ca2+ homeostasis. Recent studies indicate that TRPM8 channels are
      aberrantly expressed and required for cellular proliferation in pancreatic
      adenocarcinoma. However, the functional significance of TRPM8 in pancreatic
      tissues is mostly unknown. The objectives of this study are to examine the
      expression of TRPM8 in various histopathological types of pancreatic tissues,
      determine its clinical significance in pancreatic adenocarcinoma, and investigate
      its functional role in cancer cells invasion. We present evidence that, in normal
      pancreatic tissues, anti-TRPM8 immunoreactivity is detected in the centroacinar
      cells and the islet endocrine cells. In pre-malignant pancreatic tissues and
      malignant neoplasms, TRPM8 is aberrantly expressed to variable extents. In the
      majority of pancreatic adenocarcinoma, TRPM8 is expressed at moderate or high
      levels, and anti-TRPM8 immunoreactivity positively correlates with the primary
      tumor size and stage. In the pancreatic adenocarcinoma cell lines that express
      relatively high levels of TRPM8, short hairpin RNA-mediated interference of TRPM8
      expression impaired their ability of invasion. These data suggest that aberrantly
      expressed TRPM8 channels play contributory roles in pancreatic tumor growth and
      metastasis, and support exploration of TRPM8 as a biomarker and target of
      pancreatic adenocarcinoma. 

PMID- 24861975
TI  - Breaking the Gingival Epithelial Barrier: Role of the Aggregatibacter
      actinomycetemcomitans Cytolethal Distending Toxin in Oral Infectious Disease.
AB  - The Gram-negative bacterium Aggregatibacter actinomycetemcomitans is part of the
      HACEK group that causes infective endocarditis, a constituent of the oral flora
      that promotes some forms of periodontal disease and a member of the family of
      species that secrete a cytolethal distending toxin (Cdt). The family of bacteria
      that express the cdt genes participate in diseases that involve the disruption of
      a mucosal or epithelial layer. In vitro studies have shown that human gingival
      epithelial cells (HGEC) are native targets of the Cdt that typically induces DNA
      damage that signals growth arrest at the G2/M interphase of the cell cycle. The
      gingival epithelium is an early line of defense in the oral cavity against
      microbial assault. When damaged, bacteria collectively gain entry into the
      underlying connective tissue where microbial products can affect processes and
      pathways in infiltrating inflammatory cells culminating in the destruction of the
      attachment apparatus of the tooth. One approach has been the use of an ex vivo
      gingival explant model to assess the effects of the Cdt on the morphology and
      integrity of the tissue. The goal of this review is to provide an overview of
      these studies and to critically examine the potential contribution of the Cdt to
      the breakdown of the protective gingival barrier. 

PMID- 24861978
TI  - Bone formation in sinus augmentation procedures using autologous bone, porcine
      bone, and a 50 : 50 mixture: a human clinical and histological evaluation at 2
      months.
AB  - OBJECTIVES: The aim of this study was to perform a 2 months clinical and
      histological comparison of autologous bone, porcine bone, and a 50 : 50 mixture
      in maxillary sinus augmentation procedures. MATERIALS AND METHODS: A total of 10
      consecutive patients, undergoing two-stage sinus augmentation procedures using
      100% autologous bone (Group A), 100% porcine bone (Group B), and a 50 : 50
      mixture of autologous and porcine bone (Group C) were included in this study.
      After a 2-month healing period, at the time of implant insertion, clinical
      evaluation was performed and bone core biopsies were harvested and processed for
      histological analysis. RESULTS: The postoperative healing was uneventful
      regardless of the materials used for the sinus augmentation procedures. The
      histomorphometrical analysis revealed comparable percentages of newly formed
      bone, marrow spaces, and residual grafted material in the three groups.
      CONCLUSION: The clinical and histological results of this study indicated that
      porcine bone alone or in combination with autologous bone are biocompatible and
      osteoconductive materials and can be successfully used in sinus augmentation
      procedures.

PMID- 24861980
TI  - Implications of storage and handling conditions on glass transition and potential
      devitrification of oocytes and embryos.
AB  - Devitrification, the process of crystallization of a formerly crystal-free,
      amorphous glass state, can lead to damage during the warming of cells. The
      objective of this study was to determine the glass transition temperature of a
      cryopreservation solution typically used in the vitrification, storage, and
      warming of mammalian oocytes and embryos using differential scanning calorimetry.
      A numerical model of the heat transfer process to analyze warming and
      devitrification thresholds for a common vitrification carrier (open-pulled straw)
      was conducted. The implications on specimen handling and storage inside the dewar
      in contact with nitrogen vapor phase at different temperatures were determined.
      The time required for initiation of devitrification of a vitrified sample was
      determined by mathematical modeling and compared with measured temperatures in
      the vapor phase of liquid nitrogen cryogenic dewars. Results indicated the glass
      transition ranged from -126  degrees C to -121  degrees C, and devitrification
      was initiated at -109  degrees C. Interestingly, samples entered rubbery state at
      -121  degrees C and therefore could potentially initiate devitrification above
      this value, with the consequent damaging effects to cell survival.
      Devitrification times were calculated considering an initial temperature of
      material immersed in liquid nitrogen (-196  degrees C), and two temperatures of
      liquid nitrogen vapors within the dewar (-50  degrees C and -70  degrees C) to
      which the sample could be exposed for a period of time, either during storage or
      upon its removal. The mathematical model indicated samples could reach glass
      transition temperatures and undergo devitrification in 30 seconds. Results of the
      present study indicate storage of vitrified oocytes and embryos in the liquid
      nitrogen vapor phase (as opposed to completely immersed in liquid nitrogen) poses
      the potential risk of devitrification. Because of the reduced time-handling
      period before samples reach critical rubbery and devitrification values, caution
      should be exercised when handling samples in vapor phase.

PMID- 24861977
TI  - TRPV1: A Potential Drug Target for Treating Various Diseases.
AB  - Transient receptor potential vanilloid 1 (TRPV1) is an ion channel present on
      sensory neurons which is activated by heat, protons, capsaicin and a variety of
      endogenous lipids termed endovanilloids. As such, TRPV1 serves as a multimodal
      sensor of noxious stimuli which could trigger counteractive measures to avoid
      pain and injury. Activation of TRPV1 has been linked to chronic inflammatory pain
      conditions and peripheral neuropathy, as observed in diabetes. Expression of
      TRPV1 is also observed in non-neuronal sites such as the epithelium of bladder
      and lungs and in hair cells of the cochlea. At these sites, activation of TRPV1
      has been implicated in the pathophysiology of diseases such as cystitis, asthma
      and hearing loss. Therefore, drugs which could modulate TRPV1 channel activity
      could be useful for the treatment of conditions ranging from chronic pain to
      hearing loss. This review describes the roles of TRPV1 in the normal physiology
      and pathophysiology of selected organs of the body and highlights how drugs
      targeting this channel could be important clinically. 

PMID- 24861979
TI  - Lung cancer risk among bricklayers in a pooled analysis of case-control studies.
AB  - Bricklayers may be exposed to several lung carcinogens, including crystalline
      silica and asbestos. Previous studies that analyzed lung cancer risk among these
      workers had several study design limitations. We examined lung cancer risk among
      bricklayers within SYNERGY, a large international pooled analysis of case-control
      studies on lung cancer and the joint effects of occupational carcinogens. For men
      ever employed as bricklayers we estimated odds ratios (OR) and 95% confidence
      intervals (CI) adjusted for study center, age, lifetime smoking history and
      employment in occupations with exposures to known or suspected lung carcinogens.
      Among 15,608 cases and 18,531 controls, there were 695 cases and 469 controls who
      had ever worked as bricklayers (OR: 1.47; 95% CI: 1.28-1.68). In studies using
      population controls the OR was 1.55 (95% CI: 1.32-1.81, 540/349 cases/controls),
      while it was 1.24 (95% CI: 0.93-1.64, 155/120 cases/controls) in hospital-based
      studies. There was a clear positive trend with length of employment (p < 0.001).
      The relative risk was higher for squamous (OR: 1.68, 95% CI: 1.42-1.98, 309
      cases) and small cell carcinomas (OR: 1.78, 95% CI: 1.44-2.20, 140 cases), than
      for adenocarcinoma (OR: 1.17, 95% CI: 0.95-1.43, 150 cases) (p-homogeneity:
      0.0007). ORs were still elevated after additional adjustment for education and in
      analyses using blue collar workers as referents. This study provided robust
      evidence of increased lung cancer risk in bricklayers. Although non-causal
      explanations cannot be completely ruled out, the association is plausible in view
      of the potential for exposure to several carcinogens, notably crystalline silica
      and to a lesser extent asbestos.

PMID- 24861981
TI  - Bortezomib-cyclophosphamide-dexamethasone (VCD) versus bortezomib-thalidomide
      dexamethasone (VTD) -based regimens as induction therapies in newly diagnosed
      transplant eligible patients with multiple myeloma: a meta-analysis.
AB  - Three-drug induction regimens have become the standard of care in newly diagnosed
      transplant-eligible multiple myeloma patients. Two frequently used protocols are
      bortezomib, cyclophosphamide and dexamethasone (VCD) and bortezomib, thalidomide
      and dexamethasone (VTD). Comparisons between the two are lacking. The present
      study aimed to identify the differences in response rate and toxicity between the
      two regimens. Databases were searched using the terms 'VTD' or 'VCD' and
      'induction regimens for newly diagnosed multiple myeloma'. Prospective trials
      evaluating initial response in transplant eligible patients were included. The
      main outcome measures were response rates and adverse events. Eight clinical
      trials were eligible for analysis. Overall 672 patients were treated with either
      VCD (n = 157) or VTD (n = 515) as induction therapy. Patients treated with VTD
      presented with a significantly higher complete/near complete response (34% vs.
      6%, P = 0.002) as well as a higher very good partial response rate or better,
      following induction therapy (62% vs. 27%, P < 0.0001). Although grade 3-4
      neurotoxicity was more frequent during VTD therapy (11% vs. 6%, P = 0.057), a
      higher incidence of overall grade 3-4 adverse events was found in the VCD-treated
      patients (74% vs. 51%, P < 0.001). VTD induction therapy may be superior in
      achieving deeper response rate following induction therapy, and is better
      tolerated.

PMID- 24861982
TI  - Synthesis of isotopically labeled 1,3-dithiane.
AB  - The 1,3-dithiane is a protected formaldehyde anion equivalent that could serve as
      a useful labeled synthon. We report a facile synthesis of 1,3-[2-(13)C]- and 1,3
      [2-(13)C, 2-(2)H2]dithiane in two steps from [(13)C]- or [(13) C, (2)H3 ]methyl
      phenyl sulfoxide. We have previously reported the high yield synthesis of
      [(13)C]methyl phenyl sulfide from [(13)C]MEOH and the oxidation of [(13)C]methyl
      phenyl sulfide to [(13)C]methyl phenyl sulfoxide. Here, we describe the facile
      exchange of deuterium from (2) H2 O into [(13)C]methyl phenyl sulfoxide to yield
      [(13)C, (2)H3]methyl phenyl sulfoxide. Thus, from [(13)C]MEOH and (2)H2O, all
      possible C2 stable isotopomers of 1,3-dithiane are available. Our synthetic route
      is also amenable to preparation of radiolabeled 1,3-dithianes.

PMID- 24861983
TI  - A 99mTc(CO)3 -labeled benzylguanidine with persistent heart uptake.
AB  - We describe the synthesis and biological evaluation of the cationic (99m)Tc
      tricarbonyl complex fac-[(99m)Tc(CO)3 (kappa(3) -L1)](+) (Tc1) anchored by a
      pyrazole-diamine-methylbenzylguanidine-based ligand (L1), as potentially useful
      for myocardial imaging. The rhenium complex fac-[Re(CO)3 (kappa(3)-L1)](+) (Re1)
      was prepared and characterized as a 'cold' surrogate of the radioactive complex.
      Cell uptake studies in a neuroblastoma cell line suggest that Tc1 uptake
      mechanism is related to the norepinephrine transporter (NET). Tissue distribution
      studies in CD1 mice showed that Tc1 presents high initial heart uptake and a slow
      washout from the heart (7.8 +/- 1.3% injected dose per gram (ID/g), 30-min post
      injection (p.i.); 6.3 +/- 1.3% ID/g, 60-min p.i.), with heart to blood ratios of
      11.8 and 9.0 at 30- and 60-min p.i., respectively. The uptake mechanism of Tc1
      appears to be similar to that of metaiodobenzylguanidine (MIBG), as it can be
      reduced by coinjection with nonradioactive MIBG. The biodistribution profile of
      Tc2, where the benzylguanidine pharmacophore is absent, corroborates the fact
      that Tc1 does not accumulate in the heart by a simple diffusion mechanism but
      rather by a NET-mediated mechanism. The results confirm those obtained in the
      cell assays. Despite the persistent heart uptake found for Tc1, the high hepatic
      and renal uptake remains to be improved.

PMID- 24861986
TI  - No exacerbation of perihematomal edema with intraclot urokinase in patients with
      spontaneous intracerebral hemorrhage.
AB  - BACKGROUND: Perihematomal edema (PHE) can worsen patient outcomes after
      spontaneous intracerebral hemorrhage (ICH). Minimally invasive surgery (MIS) in
      combination with thrombolytic removal of hematoma has been proven to be a
      promising treatment strategy. However, preclinical studies have suggested that
      intraclot thrombolysis may exacerbate PHE after ICH. Herein, we investigated the
      effects of MIS and urokinase on PHE. METHODS: ICH patients were retrospectively
      identified from our institutional ICH database. Computerized volumetric analysis
      was applied to assess changes in both ICH and PHE volumes using computed
      tomographic (CT) scans of T1 (pre-MIS) and T2 (post-MIS) time points. Relative
      PHE (rPHE) was calculated as a ratio of PHE and T1 ICH volume. RESULTS: Data from
      60 MIS plus urokinase (MIS + U), 20 MIS aspiration only (MO), and 30 control
      patients were analyzed. The ICH volume, PHE volume and rPHE on T2 CT in both MIS
      + U and MO groups significantly decreased as compared with the control group (ICH
      volume, 13.7 +/- 5.7 ml, 17.0 +/- 10.5 ml vs. 30.5 +/- 10.3 ml, P < 0.01; PHE
      volume, 36.5 +/- 18.9 ml, 32.2 +/- 17.5 ml vs. 45.4 +/- 16.0 ml, P < 0.01; rPHE,
      0.9 +/- 0.4, 0.8 +/- 0.4 vs.1.4 +/- 0.5, P < 0.01). Between the MIS + U and MO
      groups, the ICH volume, PHE volume and rPHE at T2 trended towards similarity, but
      was not significant (P = 0.09, P = 0.40, P = 0.43). Furthermore, we found a
      significant correlation between the percent of ICH removal and PHE reduction (r =
      0.59, P < 0.01). There was no correlation between the cumulative dose of
      urokinase and either T2 PHE volume (r = 0.19; P = 0.16) or T2 rPHE (r = -0.12; P
      = 0.37). CONCLUSIONS: Hematoma evacuation using MIS leads to a significant
      reduction in PHE. Furthermore, the use of urokinase does not exacerbate PHE,
      making its hypothesized proedematous effects unlikely when the thrombolytic is
      administered directly into the clot.

PMID- 24861987
TI  - Analytical anatomy: quantifying surgical access with and without orbital bar
      removal: cadaver and surgical phantom studies--reply.

PMID- 24861984
TI  - Optimization of the preparation of fluorine-18-labeled steroid receptor ligands
      16alpha-[18F]fluoroestradiol (FES), [18F]fluoro furanyl norprogesterone (FFNP),
      and 16beta-[18F]fluoro-5alpha-dihydrotestosterone (FDHT) as radiopharmaceuticals.
AB  - Fluorine-18-labeled steroid receptor tracers, 16alpha-[(18)F]fluoroestradiol
      (FES), [(18)F]fluoro furanyl norprogesterone (FFNP), and 16beta-[(18)F]fluoro
      5alpha-dihydrotestosterone (FDHT), are important imaging tools for studies of
      breast and prostate cancers using positron emission tomography (PET). The
      automated production of these ligands with high specific activity (SA) as
      radiopharmaceuticals requires modification and optimization of the currently
      reported methods. [(18)F]FES with high SA was synthesized in over 60%
      radiochemical yield (RCY) at the end of synthesis (EOS) using a small amount of
      precursor (1) (as low as 0.3 mg) and 1 M H2SO4 for deprotection of the
      intermediate (2). [(18)F]FFNP was synthesized in up to 77% RCY at EOS using the
      triflate precursor (4) at room temperature or in 25% RCY using the mesylate
      precursor (6) at 65 degrees C. Both methods are highly reproducible and afford
      high SA. [(18)F]FDHT was synthesized by radiofluoride incorporation at room
      temperature, reduction with NaBH4 , and deprotection with HCl/acetone, giving
      [(18)F]FDHT in up to 75% yield (RCY). All of these methods can be easily
      translated to automated production. The information provided here will aid in the
      development of automated production of these steroid receptor tracers with high
      or improved yields, optimal SA, and ease of processing for research and clinical
      use.

PMID- 24861989
TI  - Site-specific growth of a Pt shell on Au nanoplates: tailoring their surface
      plasmonic behavior.
AB  - In this report, we tune the surface plasmonic behavior of Au nanoplates depending
      on the morphology of the Pt shell in which Pt is considered as a less optically
      inactive element. We describe the synthesis of flat Au nanoplates coated with Pt
      via rim-preferential or uniform growth methods. Depending on the site-selective
      growth of Pt on core Au nanoplates, the aspect ratio of the resulting Au@Pt
      nanoplates was tunable and their corresponding surface plasmon resonance (SPR)
      bands were controlled accordingly. Although Pt is regarded as an optically weak
      component in visible and near infrared spectral windows, a Pt coating affects the
      SPR behavior of core Au nanoplates due to effective surface plasmon (SP) coupling
      between the Au core and the deposited Pt shell. We systematically investigated
      the optical properties of uniformly grown (Au@Pt(uni)) and rim-preferentially
      grown (Au@Pt(rim)) Au@Pt nanoplates by observing their SPR band shifts compared
      to SPR of Au nanoplates. Due to the structural rigidity conferred by the Pt
      coating, the Au@Pt nanoplates can be easily transferred to the investigated
      solvents. 

PMID- 24861990
TI  - Restless leg syndrome associated with atypical antipsychotics: current status,
      pathophysiology, and clinical implications.
AB  - Restless leg syndrome (RLS) is a common disorder, frequently of unclear origin,
      which is often associated with significant distress. There are a few case reports
      of atypical antipsychotic agents (AAP) causing RLS. The pathophysiological
      mechanisms resulting in emergence of these movements suggest central dopaminergic
      dysfunction. Dopamine agonists and L-dopa reduce the symptoms of RLS, and some
      agents that block the dopaminergic system aggravate RLS. Genetic influences are
      implicated in RLS and an association between gene polymorphisms and antipyschotic
      associated onset of RLS has been postulated. Greater awareness of potential
      causes of RLS, and its differentiation from akathisia and illness related
      agitation might help in reducing the distress associated with it and improving
      patient compliance in patients using atypical antipsychotic agents. 

PMID- 24861988
TI  - Ultrasound assessment of the diaphragm: Preliminary study of a canine model of X
      linked myotubular myopathy.
AB  - INTRODUCTION: We tested the feasibility of using neuromuscular ultrasound for non
      invasive real-time assessment of diaphragmatic structure and function in a canine
      model of X-linked myotubular myopathy (XLMTM). METHODS: Ultrasound images in 3
      dogs [wild-type (WT), n=1; XLMTM untreated, n=1; XLMTM post-AAV8-mediated MTM1
      gene replacement, n=1] were analyzed for diaphragm thickness, change in thickness
      with respiration, muscle echogenicity, and diaphragm excursion amplitude during
      spontaneous breathing. RESULTS: Quantitative parameters of diaphragm structure
      were different among the animals. WT diaphragm was thicker and less echogenic
      than the XLMTM control, whereas the diaphragm measurements of the MTM1-treated
      XLMTM dog were comparable to those of the WT dog. CONCLUSIONS: This pilot study
      demonstrates the feasibility of using ultrasound for quantitative assessment of
      the diaphragm in a canine model. In the future, ultrasonography may replace
      invasive measures of diaphragm function in canine models and in humans for non
      invasive respiratory monitoring and evaluation of neuromuscular disease.

PMID- 24861991
TI  - Incidence of type 2 diabetes among patients exposed to the combination of
      pravastatin and paroxetine.
AB  - PURPOSE: This study evaluated the effects of concomitant pravastatin and
      paroxetine use on the incidence of Type 2 Diabetes Mellitus (T2DM). METHODS: A
      new-user retrospective cohort design was employed using data selected from US
      health insurance claims databases (OptumInsight and MarketScan) between July 1,
      2002, and December 31, 2009. Patients included were of age >=18; newly prescribed
      pravastatin or paroxetine; and enrolled in the database for >=180 days prior to
      the index date (i.e., first prescription of incident drug). Patients were
      assigned to either incident pravastatin or incident paroxetine user groups.
      Patients were followed until the study endpoint (T2DM), discontinuation of
      incident drug, second drug, or end of study/patient data. Cox proportional
      hazards models compared T2DM in users of pravastatin who were also taking
      paroxetine at index the date (combination users) versus pravastatinonly users. A
      similar analysis among users of paroxetine evaluated the use or non-use of
      pravastatin at index date. RESULTS: OptumInsight yielded 288,678 incident users
      of pravastatin or paroxetine; 443,137 were identified in MarketScan. The risk of
      T2DM among combination users compared to incident pravastatin only users was 1.05
      (95% CI: 0.76, 1.44) and 0.94 (95% CI: 0.90, 0.97) in OptumInsight and
      MarketScan, respectively. The risk of T2DM among combination users compared to
      incident paroxetine only users was 1.03 (95% CI: 0.69, 1.54) in OptumInsight and
      1.02 (95% CI: 0.97, 1.07) in MarketScan. CONCLUSION: The results indicate no
      increase in the risk of T2DM due to combined use of pravastatin and paroxetine
      compared to individual use of the two drugs; however, this study is limited by
      short mean follow-up.

PMID- 24861992
TI  - Alpha-1 adrenergic antagonists induced severe rhinitis in patients with benign
      prostatic hyperplasia.
AB  - The standard gold care medications for benign prostatic hyperplasia (BPH) are the
      alpha-1-adrenergic antagonists, they are an effective medications and are
      generally well tolerated. However, at this time, no data have been published
      concerning the development of severe rhinorrhea with a great impact on quality of
      life in patients treated with alpha-1-adrenergic antagonists. We report two men
      with BPH treated with two different alpha-adrenergic antagonists; alfuzosin and
      doxazocin. The naranjo quality scale documented a probable adverse drug reaction
      (score 7) between rhinorrhea and treatment with alpha-1-adrenergic antagonists.
      In conclusion we reported that alpha-1-adrenergic antagonists are able to induce
      rhinorrhea in patients with BPH. 

PMID- 24861993
TI  - Desensitization protocol for rituximab-induced serum sickness.
AB  - Rituximab, a chimeric anti-CD20 monoclonal antibody, is used to treat
      rheumatologic and hematologic diseases. Serum sickness, a Type III delayed
      hypersensitivity reaction, has been reported with rituximab treatment.
      Traditionally, drug desensitization has been used to treat Type I IgE-mediated
      hypersensitivity reactions. We report the first case of successful drug
      desensitization to rituximab in a patient with medication-induced serum sickness.
      In our case, a 37-year-old woman with Sjogren's syndrome and papillary thyroid
      carcinoma developed serum sickness 72 hours following rituximab infusion for
      gastric mucosal associated lymphoma tissue (MALT). Her MALT progressed after
      stopping rituximab. She underwent a rapid 12-step intravenous rituximab
      desensitization without recurrence of serum sickness. Following the completion of
      4 rituximab desensitizations, she had gastric MALT remission. She received 25
      maintenance rituximab doses using this desensitization protocol quarterly without
      complications. This is the first report documenting rituximab desensitization for
      the treatment of delayed drug reactions like serum sickness. 

PMID- 24861994
TI  - Appropriate utilization of restricted antibiotics in a general hospital of a
      perfecture area in Greece.
AB  - INTRODUCTION: Over-consumption of antibiotics has led to increased bacterial
      resistance and higher prevalence of hospital -acquired infections, resulting in
      rising treatment costs and prolonged length of hospital stay. The purpose of the
      study was to correlate the use of restricted antibiotics with recommended
      diagnosis and cost. MATERIALS AND METHODS: All restricted antibiotics that were
      administered in a 240-bed general hospital in a semi-urban area within a year
      were recorded. The reason for administering each such antibiotic during the first
      three months of the study was also recorded. PASW 18 (SPSS Inc.) was used for the
      statistical analysis; a variable was considered statistically significant when
      statistical significance was p= 0.05. RESULTS: 1118 patients were registered, of
      which 35,05% were employees, insured with IKA, 33,05% were farmers and covered by
      OGA and 31,9% were insured in other Social Insurance Funds or uninsured. The most
      commonly administered antibiotic combination was that of piperacillin/tazobactam,
      which was mainly used in the Internal Medicine Dept. of the Hospital. The most
      commonly used restricted antibiotic, administered after an antibiogram, was the
      combination of piperacillin/tazobactam (n= 13), mainly prescribed for respiratory
      infection. One third of the recorded restricted antibiotics were administered
      before an antibiogram had been taken for fever of unknown origin (n= 128).
      CONCLUSION: Rational use of restricted antibiotics is an important component of
      public health policies aiming at reducing hospital-acquired infections.
      Hospitalization costs rise when restricted antibiotics are used, and the
      possibility for the development of resistant bacteria increases.

PMID- 24861995
TI  - Opinion dynamics on interacting networks: media competition and social influence.
AB  - The inner dynamics of the multiple actors of the informations systems - i.e,
      T.V., newspapers, blogs, social network platforms, - play a fundamental role on
      the evolution of the public opinion. Coherently with the recent history of the
      information system (from few main stream media to the massive diffusion of socio
      technical system), in this work we investigate how main stream media signed
      interaction might shape the opinion space. In particular we focus on how
      different size (in the number of media) and interaction patterns of the
      information system may affect collective debates and thus the opinions'
      distribution. We introduce a sophisticated computational model of opinion
      dynamics which accounts for the coexistence of media and gossip as separated
      mechanisms and for their feedback loops. The model accounts also for the effect
      of the media communication patterns by considering both the simple case where
      each medium mimics the behavior of the most successful one (to maximize the
      audience) and the case where there is polarization and thus competition among
      media memes. We show that plurality and competition within information sources
      lead to stable configurations where several and distant cultures coexist. 

PMID- 24861997
TI  - Concurrent performance as bouts of behavior.
AB  - Log-survivor analyses of interresponse times suggest that the behavior of rats
      responding under single variable-interval schedules is organized into bouts
      (i.e., periods of engagement and disengagement). Attempts to generalize this
      analysis to the key pecking in pigeons, however, have failed to produce the
      characteristic broken-stick appearance typically obtained with rats. This failure
      may be due to a relatively low rate of reinforcement for engaging in alternative
      behavior experienced by pigeons. The present study tested this hypothesis by
      exposing four pigeons to concurrent schedules of reinforcement for key pecking,
      first without a changeover delay (COD) and then with a COD. In this arrangement,
      one of the concurrent options was treated as the target response and the rate of
      reinforcement for that option was manipulated across conditions. The other option
      provided explicit reinforcement for engaging in an alternative response (i.e.,
      explicit reinforcement for disengaging from the target response). In the absence
      of a COD, log-survivor plots for three of the pigeons were approximately linear,
      thus providing no evidence that responding was organized into bouts. When a COD
      was present, plots were broken stick in appearance, indicating a bout structure
      had been generated in the pigeons' behavior. Both bout length and the rate of
      bout initiations were a function of differences in rate of reinforcement. These
      data suggest that behavior may become organized into bouts when contingencies
      create sufficiently long visits to both the target behavior and the extraneous
      behavior. Fits of a double-exponential model deviated systematically from the
      actual plots due to the presence of a plateau between the two limbs. An
      alternative, double-gamma, model was explored, and it provided a considerably
      better fit than did the double-exponential. 

PMID- 24861996
TI  - Association of ABCB1, CYP3A4, EPHX1, FAS, SCN1A, MICA, and BAG6 polymorphisms
      with the risk of carbamazepine-induced Stevens-Johnson syndrome/toxic epidermal
      necrolysis in Chinese Han patients with epilepsy.
AB  - OBJECTIVE: This study explored the association between the risk of carbamazepine
      (CBZ)-induced Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) and
      CBZ dose, dose-adjusted concentration, and ABCB1, CYP3A4, EPHX1, FAS, SCN1A,
      MICA, and BAG6 polymorphisms in patients of Han ethnicity with epilepsy who were
      living in northeastern China. MATERIALS AND METHODS: We determined the genotypes
      of patients with CBZ-SJS/TEN and CBZ-tolerant patients, who were used as
      controls, for ABCB1, CYP3A4, EPHX1, FAS, SCN1A, MICA, and BAG6 polymorphisms by
      polymerase chain reaction (PCR) amplification and direct sequencing. We measured
      the steady-state serum CBZ concentrations using fluorescence polarization
      immunoassay for the control patients. RESULTS: We observed statistically
      significant differences in EPHX1 c.337T>C polymorphisms between patients with CBZ
      SJS/TEN and CBZ-tolerant controls in terms of allelic and genotypic frequencies
      (p = 0.011 and p = 0.007, respectively). The C allele and the C-G diplotype of
      EPHX1 may play important roles in increasing the risk of CBZ-SJS/TEN development
      (odds ratio [OR] 0.478, 95% confidence interval [CI] = 0.267-0.855, p = 0.011; OR
      = 0.213, 95% CI = 0.049-0.930, p = 0.025, respectively). We did not observe any
      significant associations between ABCB1, CYP3A4, EPHX1, FAS, SCN1A, MICA or BAG6
      genes and CBZ dose or dose-adjusted concentration in CBZ-tolerant patients.
      SIGNIFICANCE: We found a significant association between EPHX1 c.337T>C
      polymorphisms and the development of CBZ-SJS/TEN in patients of Han ethnicity
      living in northeastern China. EPHX1 c.337T>C polymorphisms may contribute to the
      risk of severe CBZ-SJS/TEN by increasing the concentration of a CBZ metabolite,
      CBZ-10,11-epoxide, in patients with epilepsy.

PMID- 24861998
TI  - Development of a time-dependent numerical model for the assessment of non
      stationary pharyngoesophageal tissue vibrations after total laryngectomy.
AB  - Laryngeal cancer due to, e.g., extensive smoking and/or alcohol consumption can
      necessitate the excision of the entire larynx. After such a total laryngectomy,
      the voice generating structures are lost and with that the quality of life of the
      concerning patients is drastically reduced. However, the vibrations of the
      remaining tissue in the so called pharyngoesophageal (PE) segment can be applied
      as alternative sound generator. Tissue, scar, and geometric aspects of the PE
      segment determine the postoperative substitute voice characteristic, being highly
      important for the future live of the patient. So far, PE-dynamics are simulated
      by a biomechanical model which is restricted to stationary vibrations, i.e.,
      variations in pitch and amplitude cannot be handled. In order to investigate the
      dynamical range of PE-vibrations, knowledge about the temporal processes during
      substitute voice production is of crucial interest. Thus, time-dependent model
      parameters are suggested in order to quantify non-stationary PE-vibrations and
      drawing conclusions on the temporal characteristics of tissue stiffness,
      oscillating mass, pressure, and geometric distributions within the PE-segment. To
      adapt the numerical model to the PE-vibrations, an automatic, block-based
      optimization procedure is applied, comprising a combined global and local
      optimization approach. The suggested optimization procedure is validated with 75
      synthetic data sets, simulating non-stationary oscillations of differently shaped
      PE-segments. The application to four high-speed recordings is shown and
      discussed. The correlation between model and PE-dynamics is >= 97%.

PMID- 24861999
TI  - Economical production of poly(epsilon-l-lysine) and poly(l-diaminopropionic acid)
      using cane molasses and hydrolysate of streptomyces cells by Streptomyces albulus
      PD-1.
AB  - Poly(epsilon-L-lysine) (epsilon-PL) and poly(L-diaminopropionic acid) (PDAP) co
      production by Streptomyces albulus PD-1 from cane molasses and hydrolysate of
      strepyomyces cells (HSC) was investigated for the first time in this study. The
      optimal initial total sugar concentration of the cane molasses pretreated with
      sulfuric acid was determined to be 20 g L(-1), and HSC could substitute for yeast
      extract for epsilon-PL and PDAP co-production. When fed-batch fermentation was
      performed in 1t fermentor with pretreated cane molasses and HSC, 20.6 +/- 0.5 g
      L(-1) of epsilon-PL and 5.2 +/- 0.6 g L(-1) of PDAP were obtained. The amount of
      strepyomyces cells obtained in one fed-batch fermentation is sufficient to
      prepare the HSC to satisfy the demand of subsequent fermentations, thus the self
      cycling of organic nitrogen source becomes available. These results suggest that
      the low-cost cane molasses and HSC can be used for the economical production of
      epsilon-PL and PDAP by S. albulus PD-1.

PMID- 24862000
TI  - A new polymer-based laccase for decolorization of AO7: long-term storage and
      mediator reuse.
AB  - To address the bottlenecks of laccase-based catalysis, i.e., poor long-term
      stability and potential secondary pollution caused by synthetic mediator, we
      fabricated a new biocatalyst (N-PS-Lac) through adsorption of laccase onto
      polystyrene anion exchangers (N-PS) binding quaternary ammonium groups. After 2
      year storage, the residual activity of N-PS-Lac remained as high as 101.7%, while
      that for native laccase was only 14.6%. Also, N-PS-Lac exhibited improved
      durability against pH variation and thermal treatment at 60 degrees C. Gaussian
      curve fitting of FT-IR spectra indicated that laccase conformation of N-PS-Lac
      was rigidified, possibly because of the host geometric restriction and the host
      laccase electrostatic attraction. A two-step method, i.e., adsorption of an azo
      dye AO7 by N-PS and then ectopic degradation by the immobilized laccase, was
      proposed to reuse the mediator HOBT for seven cyclic runs, where N-PS-Lac kept
      the constant decolorization efficiency. AO7 solution was detoxified completely
      after decolorization by the two-step method. 

PMID- 24862001
TI  - Effects of inoculum type and bulk dissolved oxygen concentration on achieving
      partial nitrification by entrapped-cell-based reactors.
AB  - An entrapment of nitrifiers into gel matrix is employed as a tool to fulfill
      partial nitrification under non-limiting dissolved oxygen (DO) concentrations in
      bulk solutions. This study aims to clarify which of these two attributes,
      inoculum type and DO concentration in bulk solutions, is the decisive factor for
      partial nitrification in an entrapped-cell based system. Four polyvinyl alcohol
      entrapped inocula were prepared to have different proportions of nitrite
      oxidizing bacteria (NOB) and nitrite-oxidizing activity. At a DO concentration of
      3 mg l(-1), the number of active NOB cells in an inoculum was the decisive factor
      for partial nitrification enhancement. However, when the DO concentration was
      reduced to 2 mg l(-1), all entrapped cell inocula showed similar degrees of
      partial nitrification. The results suggested that with the lower bulk DO
      concentration, the preparation of entrapped cell inocula is not useful as the DO
      level becomes the decisive factor for achieving partial nitrification.

PMID- 24862003
TI  - Physiological and electrochemical effects of different electron acceptors on
      bacterial anode respiration in bioelectrochemical systems.
AB  - To understand the interactions between bacterial electrode respiration and the
      other ambient bacterial electron acceptor reductions, alternative electron
      acceptors (nitrate, Fe2O3, fumarate, azo dye MB17) were added singly or multiply
      into Shewanella decolorationis microbial fuel cells (MFCs). All the added
      electron acceptors were reduced simultaneously with current generation. Adding
      nitrate or MB17 resulted in more rapid cell growth, higher flavin concentration
      and higher biofilm metabolic viability, but lower columbic efficiency (CE) and
      normalized energy recovery (NER) while the CE and NER were enhanced by Fe2O3 or
      fumarate. The added electron acceptors also significantly influenced the cyclic
      voltammetry profile of anode biofilm probably via altering the cytochrome c
      expression. The highest power density was observed in MFCs added with MB17 due to
      the electron shuttle role of the naphthols from MB17 reduction. The results
      provided important information for MFCs applied in practical environments where
      contains various electron acceptors. 

PMID- 24862002
TI  - Biosorption of chromium by alginate extraction products from Sargassum
      filipendula: investigation of adsorption mechanisms using X-ray photoelectron
      spectroscopy analysis.
AB  - The alginate extraction products from Brazilian brown seaweed Sargassum
      filipendula were studied for chromium biosorption. Batch experiments were
      conducted at pH 2 and 3 and 20 degrees C to determine the sorption capacity of
      this biosorbents for chromium (VI) and (III). The biomass was characterized
      before and after metal binding by X-ray photoelectron spectroscopy (XPS) in order
      to determine the mechanisms of chromium biosorption. The residue has a high
      adsorption capacity, close the value obtained with seaweed and higher than that
      of alginate for both Cr(III) and Cr(VI). XPS analysis of the biosorbents revealed
      that carboxyl, amino and sulfonate groups are responsible for the binding of the
      metal ions. The analysis also indicated that the Cr(VI) bound to the biomass was
      reduced to Cr(III). 

PMID- 24862004
TI  - Enhancement of n-butanol production by in situ butanol removal using permeating
      heating-gas stripping in acetone-butanol-ethanol fermentation.
AB  - Butanol recovery from acetone-butanol-ethanol (ABE) fed-batch fermentation using
      permeating-heating-gas was determined in this study. Fermentation was performed
      with Clostridium acetobutylicum B3 in a fibrous bed bioreactor and permeating
      heating-gas stripping was used to eliminate substrate and product inhibition,
      which normally restrict ABE production and sugar utilization to below 20 g/L and
      60 g/L, respectively. In batch fermentation (without permeating-heating-gas
      stripping), C. acetobutylicum B3 utilized 60 g/L glucose and produced 19.9 g/L
      ABE and 12 g/L butanol, while in the integrated process 290 g/L glucose was
      utilized and 106.27 g/L ABE and 66.09 g/L butanol were produced. The intermittent
      gas stripping process generated a highly concentrated condensate containing
      approximately 15% (w/v) butanol, 4% (w/v) acetone, a small amount of ethanol
      (<1%), and almost no acids, resulting in a highly concentrated butanol solution
      [~ 70% (w/v)] after phase separation. Butanol removal by permeating-heating-gas
      stripping has potential for commercial ABE production.

PMID- 24862005
TI  - Forming microbial anodes with acetate addition decreases their capability to
      treat raw paper mill effluent.
AB  - Microbial anodes were formed under polarization at -0.3 V/SCE on graphite plates
      in effluents from a pulp and paper mill. The bioanodes formed with the addition
      of acetate led to the highest current densities (up to 6A/m(2)) but were then
      unable to oxidize the raw effluent efficiently (0.5A/m(2)). In contrast, the
      bioanodes formed without acetate addition were fully able to oxidize the organic
      matter contained in the effluent, giving up to 4.5A/m(2) in continuous mode.
      Bacterial communities showed less bacterial diversity for the acetate-fed
      bioanodes compared to those formed in raw effluents. Deltaproteobacteria were the
      most abundant taxonomic group, with a high diversity for bioanodes formed without
      acetate addition but with almost 100% Desulfuromonas for the acetate-fed
      bioanodes. The addition of acetate to form the microbial anodes induced microbial
      selection, which was detrimental to the treatment of the raw effluent.

PMID- 24862006
TI  - Enhanced fermentability of poplar by combination of alkaline peroxide
      pretreatment and semi-simultaneous saccharification and fermentation.
AB  - To improve ethanol productivity with few inhibitors generated, a novel process of
      combined alkaline peroxide (AP) pretreatment and semi-simultaneous
      saccharification and fermentation (SSSF) was developed in this work. Pretreatment
      with 10% (g H2O2/g wood) H2O2 at 160 degrees C for 2h followed by SSSF was found
      to be the optimal combination with remarkably increased ethanol yield. The
      proposed process resulted in 63.1% of ethanol yield, which was about five times
      more than that of the untreated sample that was processed using conventional
      simultaneous saccharification and fermentation (SSF). The efficient conversion
      was ascribed to the high delignification efficiency (64.9%) of AP pretreatment,
      which led to incompact structure and generation of fewer inhibitors during SSSF
      (c. 6g/L of lactic acid) than SSF (c. 10 g/L of lactic acid). This combined
      approach was proved to be an effective method for the promotion of the
      bioconversion of lignocellulosic materials.

PMID- 24862007
TI  - Bacteria induced degradation of fluoranthene in minimal salt medium mediated by
      catabolic enzymes in vitro condition.
AB  - Fluoranthene is highly toxic and ubiquitous in the environment. A study on
      degradation of 200 ppm of fluoranthene in MSM by two bacterial strains
      Pseudomonas aeruginosa PSA5, Rhodococcus sp. NJ2 and their consortium revealed
      that fluoranthene was degraded 74% by Rhodococcus sp. NJ2, 61% by Pseudomonas sp.
      PSA5 and 97% by their consortium. Higher degradation in the consortium may be
      attributed to synergistic action between two bacteria. It was also observed that
      several degradative enzymes catechol 1,2 dioxygenase, catechol 2,3 dioxygenase,
      protocatechuate 2,3 dioxygenase, protocatechuate 3,4 dioxygenase, protocatechuate
      4,5 dioxygenase, salicylate hydroxylase and 2-carboxybenzaldehyde dehydrogenase
      were differentially induced at different stages of fluoranthene degradation.
      Biodegradation kinetics indicated half life period of fluoranthene degradation.
      Besides, glycolipid, as a biosurfactant, was induced to facilitate the
      degradation process. Hence, both the bacteria may be used individually or in
      combination for effective decontamination of oil and sludge contaminated soil.

PMID- 24862008
TI  - Challenges and approaches for high-voltage spinel lithium-ion batteries.
AB  - Lithium-ion (Li-ion) batteries have been developed for electric vehicle (EV)
      applications, owing to their high energy density. Recent research and development
      efforts have been devoted to finding the next generation of cathode materials for
      Li-ion batteries to extend the driving distance of EVs and lower their cost.
      LiNi(0.5)Mn(1.5)O(4) (LNMO) high-voltage spinel is a promising candidate for a
      next-generation cathode material based on its high operating voltage (4.75 V vs.
      Li), potentially low material cost, and excellent rate capability. Over the last
      decade, much research effort has focused on achieving a fundamental understanding
      of the structure-property relationship in LNMO materials. Recent studies,
      however, demonstrated that the most critical barrier for the commercialization of
      high-voltage spinel Li-ion batteries is electrolyte decomposition and concurrent
      degradative reactions at electrode/electrolyte interfaces, which results in poor
      cycle life for LNMO/graphite full cells. Despite scattered reports addressing
      these processes in high-voltage spinel full cells, they have not been
      consolidated into a systematic review article. With this perspective, emphasis is
      placed herein on describing the challenges and the various approaches to mitigate
      electrolyte decomposition and other degradative reactions in high-voltage spinel
      cathodes in full cells.

PMID- 24862009
TI  - The association between parenting behavior and somatization in adolescents
      explained by physiological responses in adolescents.
AB  - INTRODUCTION: This study adds to the knowledge on somatization in adolescents by
      exploring its relation with parenting behavior and the mediating/moderating role
      of physiological responses in adolescents to parenting behavior. METHOD: Eighteen
      adolescents with high and 18 adolescents with low somatization scores and their
      mothers completed a discussion task, from which observed parenting behavior
      scores were derived. Skin conductance in adolescents was measured before and
      during the discussion. RESULTS: For adolescents with high levels of physiological
      responses, unadaptive parenting was related to a higher chance of high
      somatization scores. For low physiologically responsive adolescents, the relation
      between parenting behavior and somatization was not significant. CONCLUSION:
      Parenting behavior is not univocally related to somatization in adolescents, but
      the association depends on physiological responses in adolescents.

PMID- 24862010
TI  - The assessment and management of diabetes related lower limb problems in India-an
      action research approach to integrating best practice.
AB  - BACKGROUND: In this article the authors explore the current issues and barriers
      related to achieving successful outcomes to diabetic foot complications in India.
      This was achieved by engaging clinicians in taking ownership of the problems and
      facilitating them in the identification of solutions to action change in clinical
      practice. METHODS: This was accomplished through facilitating participants in
      this study via a process of problem identification and planning, the first phases
      of an action research cycle approach. The methods of data collection were focus
      groups, observations and individual conversations. The data were analysed using a
      thematic framework. RESULTS: Based on the practitioner's experiences and
      opinions, key themes were identified. These themes had the potential to inform
      the changes needed in clinical practice, to overcome barriers and embed ownership
      of the solutions. Five themes were identified highlighting: concerns over a
      fragmented service; local recognition of need; lack of standardised care
      pathways; lack of structured assessment and an absence of annual foot screening.
      Combined, the issues identified were thought to be important in preventing timely
      assessment and management of foot problems. CONCLUSION: It was unanimously agreed
      that a formalised process of foot assessment should be developed and implemented
      as part of the subsequent phases of the action research process, which the
      authors intended to take forward and report in a further paper. The aim of which
      is to guide triage, education, care pathways, audit and evaluation of outcomes.
      Facilitation of the clinicians in developing a program and screening tool to
      implement and teach these skills to others could be an important step in reducing
      the number of high-risk cases that are often resulting in the amputation of
      limbs.

PMID- 24862011
TI  - The commitment of human cells to senescence.
AB  - Fifty years ago, it was demonstrated by Leonard Hayflick that human diploid
      fibroblasts grown in culture have a finite lifespan. Since that time, innumerable
      experiments have been published to discover the mechanism(s) that are responsible
      for this 'Hayflick limit' to continuous growth. Much new information has been
      gained, but there are certain features of this experimental system which have not
      been fully understood. One is the fact that different populations of the foetal
      lung strains WI-38 and MRC-5 have a range in division potential of at least a
      millionfold. The commitment theory of cellular aging, published more than 30
      years ago, is able to explain this, but it has been consistently ignored. The
      theory predicts that bottlenecks, which are transient reductions in population
      size, can significantly reduce lifespan, or increase variability of lifespans.
      Computer simulations specify the effects of bottlenecks on longevity, and these
      were confirmed in two series of experiments. Commitment to senescence may be the
      loss of telomerase, which leads to the erosion of telomeres and the inability to
      grow indefinitely. Many experiments have been done with skin fibroblasts from
      human donors of different age, and it was originally thought that in vitro
      lifespan was inversely correlated with donor age. In these experiments, a single
      skin biopsy produces a population of cells that are grown to senescence. However,
      there is no reason to believe that skin fibroblasts are less variable in their in
      vitro lifespan than foetal lung strains, in which case the data points with skin
      cells are so variable that they may completely obscure any inverse correlation
      between culture lifespans and donor age.

PMID- 24862012
TI  - Evolutionary theories of aging can explain why we age.
AB  - Evolutionary theories of aging explain why we age. These theories take into
      account the fact that, in the wild, mean lifespan of many species is usually
      shorter than it could be in protected environments. In such conditions, because
      most of animals die before reaching old age, there is no selection in favor or
      against alleles with effects at old age. Alleles with negative effects at this
      age can thus accumulate in successive generations, particularly if they also have
      positive effects at young age and are thus retained by selection. This chapter
      describes the evolutionary theories of aging and their consequences for the
      understanding of the biology of aging as well as the challenges to these
      theories. It is argued that these theories offer a reasonable explanation to the
      existence of the aging process even if they can surely be refined.

PMID- 24862013
TI  - Control of cell replication during aging.
AB  - The observation that human fibroblasts have a limited number of cell population
      doublings in vitro led to the proposal that it is the expression of cellular
      aging. In vitro, the proliferation of human fibroblasts terminates with a
      postmitotic cell which was called senescent cell. Due to misinterpreted
      experiments, the latter was considered the hallmark of cellular aging, although
      obviously we do not age because our cells stop dividing. The so-called senescent
      cell has been the core of the investigation on cellular aging and of the theories
      proposed on the subject. The search for mechanisms responsible for the
      postmitotic state led to contradictory results, which accumulated when the term
      cell senescence was used to define the growth arrest due to a variety of causes.
      The mechanisms believed to be causing these multiple forms of cell senescence
      multiplied accordingly. This was disregarded claiming that there are multiple
      pathways to cell senescence. Since it was thought that aging favors malignant
      transformation, speculations were made to find a relationship between 'cell
      senescence' and cancers, which led to several paradoxes. The contradictions and
      paradoxes should be cleared to reestablish logic and order in the field and
      understand its relevance for human aging.

PMID- 24862015
TI  - Aging of cell membranes: facts and theories.
AB  - This chapter is intended to outline the main results of a research trend realized
      by the author during the last 45 years, focused on the main role played by the
      cell membrane in the aging process. It is a very wide field; therefore, the
      reader cannot expect in this limited space a detailed description, but will be
      given a wide, interdisciplinary insight into the main facts and theories
      regarding cellular aging. The central idea described here is the concept called
      the membrane hypothesis of aging (MHA). The history, the chemical roots,
      physicochemical facts, biophysical processes, as well as the obligatory
      biochemical consequences are all touched in by indicating the most important
      sources of detailed knowledge for those who are more interested in the basic
      biology of the aging process. This chapter covers also the available anti-aging
      interventions on the cell membrane by means of the centrophenoxine treatment
      based on the MHA. It also briefly interprets the possibilities of a just
      developing anti-aging method by using the recombinant human growth hormone,
      essential basis of which is the species specificity, and the general presence of
      receptors of this hormone in the plasma membrane of all types of cells.

PMID- 24862014
TI  - Cell senescence: role in aging and age-related diseases.
AB  - Cell senescence is one of the major paradigms of aging research. It started with
      the demonstration by L. Hayflick of the limited number of divisions by normal,
      nontransformed cells, not shown by transformed malignant cells, this processes
      being largely regulated by the telomere-telomerase system. A complete renewal of
      this discipline came from the demonstration that cells can enter senescence at
      any time by an anti-oncogene-triggered pathway, enabling them to escape
      malignancy. The senescent cell became a major actor of the aging process, among
      others, by the acquisition of the senescence-associated secretory phenotype. This
      chapter is devoted to the regulatory process involved in the acquisition of the
      senescent cell phenotype and its role in organismal aging.

PMID- 24862016
TI  - Oxidative stress, mitochondrial dysfunction and the mitochondria theory of aging.
AB  - Aging is characterized by a progressive decline in cellular function, organismal
      fitness and increased risk of age-associated diseases and death. One potential
      cause of aging is the progressive accumulation of dysfunctional mitochondria and
      oxidative damage with age. Considerable efforts have been made in our
      understanding of the role of mitochondrial dysfunction and oxidative stress in
      aging and age-associated diseases. This chapter outlines the interplay between
      oxidative stress and mitochondrial dysfunction, and discusses their impact on
      senescence, cell death, stem cell function, age-associated diseases and
      longevity.

PMID- 24862017
TI  - Aging of connective tissues: experimental facts and theoretical considerations.
AB  - In this chapter, we describe in detail the age-dependent modifications of
      connective tissues, separately for their cellular and extracellular compartments.
      Cell aging was studied by the in vitro method established by Hayflick as well as
      by ex vivo explant cultures, and results with both methods are discussed. Follows
      then the description of age changes of macromolecular components of extracellular
      matrix as well as the decline with age of receptor-mediated cell-matrix
      interactions. These interactions mediated by several types of receptors, as
      integrins, the elastin receptor and others, play a crucial role for the
      definition and regulation of the differentiated cell phenotype. Age-related
      modifications of both matrix components and receptors are discussed in order to
      explain the mechanisms of the age-dependent modulations of cell-matrix
      interactions. Finally, we discuss the relations between age changes of matrix
      components and the onset of age-related diseases, especially cardiovascular
      pathologies mostly involved in age-dependence of functions and limitation of
      longevity.

PMID- 24862018
TI  - Aging of cell communication: loss of receptor function.
AB  - Communication between cells is the most important evolutionarily conserved
      mechanism which enabled the bioconstruction of multicellular organisms. These
      mechanisms all comprise some general properties such as specific receptors
      recognized by agonists, molecules capable of activating them as well as the
      intracellular signalling pathways which activate the effector functions. A large
      number of such receptors and transmission pathways have been described, and both
      agonists and antagonists have been identified and are used in medicine. A more
      recent discovery was the demonstration that several receptor-mediated functions
      decline with age because either of the loss of receptors or their uncoupling from
      their specific signalling pathways. The mechanisms and biological as well as
      pathological consequences of this age-dependent receptor loss and signal
      transduction changes are described in this chapter.

PMID- 24862019
TI  - On the immunological theory of aging.
AB  - Aging is a complex phenomenon the cause of which is not fully understood, despite
      the plethora of theories proposed to explain it. As we age, changes in
      essentially all physiological functions, including immunity, are apparent. Immune
      responses decrease with aging, contributing to the increased incidence of
      different chronic diseases with an inflammatory component (sometimes referred to
      as 'inflamm-aging'). It is clear from many studies that human longevity may be
      influenced by these changes in the immune system, but how they proceed is not
      clearly determined. In this chapter, we will review the age-related changes in
      the immune response and assess the validity of the immune theory of aging (i.e.
      that these changes in immune response are the primary cause of aging). Many data
      in humans support the notion that age-associated immune dysfunction may at least
      in part explain the aging process. Explanatory power may be enhanced by
      combination with other theories such as the free radical theory. More
      longitudinal studies are needed to corroborate the immune theory of aging.

PMID- 24862020
TI  - Aging of the brain, dementias, role of infectious proteins: facts and theories.
AB  - Neurodegenerative diseases, including Alzheimer's, Parkinson's and prion diseases
      are a major and growing public health issue for aging populations as aging is the
      greatest risk factor for neurodegeneration. Protein misfolding and spreading are
      common to these neurodegenerative diseases. There are many high-quality reviews
      concerning these diseases; also in this brief chapter, I have tried to give a
      summary of the principal points involved in the pathogenesis of these three
      clinical entities.

PMID- 24862021
TI  - Aging as alteration.
AB  - Aging is a normative biological process, and not simply a physical one. It is not
      accurate to define it by the fact that life has an entropic cost, and to
      characterize it as a pure imbalance between exergonic and endergonic reaction in
      metabolism (the free radical theory of aging) or finally as an imbalance between
      the excessive formation of reactive oxygen species and limited antioxidant
      defenses. In connective tissues, aging is alteration. And alteration is more than
      destruction or degradation. It deals with self-destruction and with the so-called
      molecular vicious circles of aging. In worms, in yeast, and in other organisms,
      aging is also opposed to longevity that counteracts this self-destruction
      process, as if longevity was something like a developmental constraint (delay)
      opposed to an evolutionary one (alteration).

PMID- 24862022
TI  - Longevity and its regulation: centenarians and beyond.
AB  - Regulation of longevity depends on genetic and environmental factors. According
      to Svanborg, a Swedish geriatrician, over the last decades human life expectancy
      increased as well as the age at onset of fatal diseases. Nevertheless, autopsies
      of centenarians revealed the presence of several severe pathologies which could
      have killed them much earlier. Therefore, the emphasis is on regulation of
      resistance dependent on the expression of genes such as Sirtuins, mTOR pathway
      and others controlling body resistance. Only a small fraction (<1%) of
      centenarians live to become supercentenarians (110 years), indicating a limit of
      performance and resistance of the body. This limit can be interpreted as
      'tinkering' of nature instead of producing masterpieces as suggested by F. Jacob.
      These facts and theories are described in this chapter.

PMID- 24862023
TI  - Aging. Facts and theories. Preface.

PMID- 24862024
TI  - Microwave ablation of a large renal aspergilloma.
AB  - Increasing numbers of immunocompromised patients have led to a corresponding rise
      in the incidence of invasive Aspergillus infections. Despite advances in
      antifungal therapy coupled with reduction in immunosuppression, invasive
      aspergillosis is associated with significant morbidity and mortality. Although
      surgical debulking has proven effective in difficult-to-treat cases, patient
      comorbidities may prevent such intervention. Non-invasive alternatives to surgery
      are needed. Microwave ablation has many advantages over other ablative
      techniques, including convection profile, faster heating time, and higher intra
      lesion temperatures, which may be associated with greater therapeutic efficacy.
      We report a case of microwave ablation as an adjunct to medical therapy in
      angioinvasive renal aspergilloma. 

PMID- 24862025
TI  - Phosphorylation of photosystem II core proteins prevents undesirable cleavage of
      D1 and contributes to the fine-tuned repair of photosystem II.
AB  - Photosystem II (PSII) is a primary target for light-induced damage in
      photosynthetic protein complexes. To avoid photoinhibition, chloroplasts have
      evolved a repair cycle with efficient degradation of the PSII reaction center
      protein, D1, by the proteases FtsH and Deg. Earlier reports have described that
      phosphorylated D1 is a poor substrate for proteolysis, suggesting a mechanistic
      role for protein phosphorylation in PSII quality control, but its precise role
      remains elusive. STN8, a protein kinase, plays a central role in this
      phosphorylation process. To elucidate the relationship between phosphorylation of
      D1 and the protease function we assessed in this study the involvement of STN8,
      using Arabidopsis thaliana mutants lacking FtsH2 [yellow variegated2 (var2)] and
      Deg5/Deg8 (deg5 deg8). In support of our presumption we found that
      phosphorylation of D1 increased more in var2. Furthermore, the coexistence of
      var2 and stn8 was shown to recover the delay in degradation of D1, resulting in
      mitigation of the high vulnerability to photoinhibition of var2. Partial D1
      cleavage fragments that depended on Deg proteases tended to increase, with
      concomitant accumulation of reactive oxygen species in the mutants lacking STN8.
      We inferred that the accelerated degradation of D1 in var2 stn8 presents a
      tradeoff in that it improved the repair of PSII but simultaneously enhanced
      oxidative stress. Together, these results suggest that PSII core phosphorylation
      prevents undesirable cleavage of D1 by Deg proteases, which causes cytotoxicity,
      thereby balancing efficient linear electron flow and photo-oxidative damage. We
      propose that PSII core phosphorylation contributes to fine-tuned degradation of
      D1.

PMID- 24862026
TI  - Renal cell carcinoma metastasis to the parathyroid gland: A very rare occurrence.
AB  - INTRODUCTION: Metastases to the parathyroid gland are very uncommon. Although
      renal cell carcinoma metastasis to the head and neck region is well recognised,
      with a predilection for unpredictable metastasis to unusual sites such as the
      thyroid gland, nose, paranasal sinuses, and cranial bones, there are no reports
      of parathyroid gland involvement. PRESENTATION OF CASE: We describe an unusual
      case of renal cell carcinoma metastasis to a parathyroid gland in a 69-year-old
      male who had been treated 8 years previously for a pT3b N0 M1 clear cell
      carcinoma of the right kidney with a right nephrectomy, and interferon
      immunotherapy for 18 months. The patient had originally presented to the plastic
      surgeons with a rapidly enlarging 3cm superficial lesion on the ventral aspect of
      the left forearm, which was excised with histology revealing metastatic renal
      (clear) cell carcinoma. DISCUSSION: Renal cell carcinoma has a reputation for
      unpredictable patterns of metastasis, and our case highlights this, with the
      first description in the literature of parathyroid gland metastasis. Despite the
      poor prognosis associated with metastatic renal cell carcinoma, our patient is
      still alive 10 years following original presentation, despite having metastasis
      to two different extra-renal sites and a shortened course of initial adjuvant
      systemic therapy. CONCLUSION: In parathyroid gland metastasis, metastectomy can
      offer excellent local long term local control.

PMID- 24862027
TI  - Laparoscopic assisted resection of a ilio-sacral chondrosarcoma: A single case
      report.
AB  - INTRODUCTION: Sacral tumor often involves en bloc surgical resection with tumor
      free margins and functional reconstruction challenges. Such a management is
      challenging because of difficulties in accessing the lesion, risks for damages of
      neighboring organs, and risks for massive blood loss. In posterior approach,
      because first elevation of the sacrum allows dissection of presacral structures,
      such risks for damages intrapelvic structures and hemorrhage are especially high.
      PRESENTATION OF CASE: We report here about a laparoscopic assisted posterior
      resection of a ilio-sacral chondrosarcoma in a women, 6 weeks after vaginal
      delivery. Primary laparoscopic approach consisted in dissection of the ureter and
      of the colon with control to the pelvic vessels and nerves and determination of
      limits of the resection. The iliac osteotomy was performed from posterior
      approach with saw and osteotomes at the predetermined extralesional level. The
      defect was replaced with a structural fresh frozen femoral allograft and
      stabilization performed by lumbo-ischial screw/rod fixation. DISCUSSION: Surgical
      time was about 360min. No intra-postoperative complications occurred. Blood loss
      was estimated to about 1000cm(3). Histologic examination of the specimen showed
      tumor-free margins. At 8 months follow-up, the patient appears to be without
      recurrence. Because of the denervation of the nerve root L5 and below, she mostly
      uses two canes, but she has a functioning quadriceps. Continence and voiding
      functions for urine and stool have fully recovered. CONCLUSION: Primary
      laparoscopic approach appeared to be a good way for preparation orthopedics
      sacroiliac resection to reduce postoperative morbidity, intraoperative blood loss
      and better assure macroscopic tumor-free margins.

PMID- 24862028
TI  - Multiple giant intra abdominal lipomas: A rare presentation.
AB  - INTRODUCTION: Solitary or multiple lipomas, composed of mature fat, represents by
      far the most common benign mesenchymal neoplasm occurring throughout the whole
      body, but they rarely originate in the intestinal mesentery. PRESENTATION OF
      CASE: A 60-year-old male presented with left sided abdominal distension and pain
      since 4 months, ultrasonography and computerized tomography abdomen was
      suggestive of multiple well-defined fat density lesions in the lower abdomen and
      pelvis. USG guided fine needle aspiration cytology was conclusive of a spindle
      cell lesion. Exploratory laparotomy was performed and multiple major fat tissue
      swellings were excised. Histopathology confirmed it to be spindle cell type of
      lipoma. DISCUSSION: Because of the silent nature the exact prevalence of lipomas
      is unknown. It can arise in any location in which fat is normally present,
      reported intra abdominal lipomas have been very rare. Clinical manifestations
      depend on the size and location of the growth. In most patients, symptoms are few
      or absent. USG and CT scan abdomen are used for the diagnosis. Complete surgical
      excision being the only treatment. CONCLUSION: Intra abdominal lipoma is a very
      rare entity, and many cases might be ignored due to their silent nature. They
      might or might not present with any symptoms. Complete surgical excision being
      the only treatment, with a very good prognosis.

PMID- 24862032
TI  - Building complex hybrid carbon architectures by covalent interconnections:
      graphene-nanotube hybrids and more.
AB  - Graphene is theoretically a robust two-dimensional (2D) sp(2)-hybridized carbon
      material with high electrical conductivity and optical transparency. However, due
      to the existence of grain boundaries and defects, experimentally synthesized
      large-area polycrystalline graphene sheets are easily broken and can exhibit high
      sheet resistances; thus, they are not suitable as flexible transparent
      conductors. As described in this issue of ACS Nano, Tour et al. circumvented this
      problem by proposing and synthesizing a novel hybrid structure that they have
      named "rebar graphene", which is composed of covalently interconnected carbon
      nanotubes (CNTs) with graphene sheets. In this particular configuration, CNTs act
      as "reinforcing bars" that not only improve the mechanical strength of
      polycrystalline graphene sheets but also bridge different crystalline domains so
      as to enhance the electrical conductivity. This report seems to be only the tip
      of the iceberg since it is also possible to construct novel and unprecedented
      hybrid carbon architectures by establishing covalent interconnections between
      CNTs with graphene, thus yielding graphene-CNT hybrids, three-dimensional (3D)
      covalent CNT networks, 3D graphene networks, etc. In this Perspective, we review
      the progress of these carbon hybrid systems and describe the challenges that need
      to be overcome in the near future. 

PMID- 24862033
TI  - The ecology of technology and nanomotors.
AB  - Ecosystems are characterized by particular scaling laws describing, for example,
      the relationship between animal abundance and species body weight. It is
      hypothesized that technological systems follow similar scaling laws, where the
      abundance of a type of machine correlates with its size. Human progress
      continuously expands the range of accessible machine sizes, creating a technology
      trend toward vast numbers of microscopic machines. Current research related to
      nanomotors, such as the report by Kumar et al. in this issue of ACS Nano
      describing advances in controlling biomolecular motors, lays the scientific
      foundation for this trend. 

PMID- 24862034
TI  - Frictional behavior of atomically thin sheets: hexagonal-shaped graphene islands
      grown on copper by chemical vapor deposition.
AB  - Single asperity friction experiments using atomic force microscopy (AFM) have
      been conducted on chemical vapor deposited (CVD) graphene grown on
      polycrystalline copper foils. Graphene substantially lowers the friction force
      experienced by the sliding asperity of a silicon AFM tip compared to the
      surrounding oxidized copper surface by a factor ranging from 1.5 to 7 over loads
      from the adhesive minimum up to 80 nN. No damage to the graphene was observed
      over this range, showing that friction force microscopy serves as a facile, high
      contrast probe for identifying the presence of graphene on Cu. Consistent with
      studies of epitaxially grown, thermally grown, and mechanically exfoliated
      graphene films, the friction force measured between the tip and these CVD
      prepared films depends on the number of layers of graphene present on the surface
      and reduces friction in comparison to the substrate. Friction results on graphene
      indicate that the layer-dependent friction properties result from puckering of
      the graphene sheet around the sliding tip. Substantial hysteresis in the normal
      force dependence of friction is observed with repeated scanning without breaking
      contact with a graphene-covered region. Because of the hysteresis, friction
      measured on graphene changes with time and maximum applied force, unless the tip
      slides over the edge of the graphene island or contact with the surface is
      broken. These results also indicate that relatively weak binding forces exist
      between the copper foil and these CVD-grown graphene sheets. 

PMID- 24862029
TI  - Insights from cerebellar transcriptomic analysis into the pathogenesis of ataxia.
AB  - IMPORTANCE: The core clinical and neuropathological feature of the autosomal
      dominant spinocerebellar ataxias (SCAs) is cerebellar degeneration. Mutations in
      the known genes explain only 50% to 60% of SCA cases. To date, no effective
      treatments exist, and the knowledge of drug-treatable molecular pathways is
      limited. The examination of overlapping mechanisms and the interpretation of how
      ataxia genes interact will be important in the discovery of potential disease
      modifying agents. OBJECTIVES: To address the possible relationships among known
      SCA genes, predict their functions, identify overlapping pathways, and provide a
      framework for candidate gene discovery using whole-transcriptome expression data.
      DESIGN, SETTING, AND PARTICIPANTS: We have used a systems biology approach based
      on whole-transcriptome gene expression analysis. As part of the United Kingdom
      Brain Expression Consortium, we analyzed the expression profile of 788 brain
      samples obtained from 101 neuropathologically healthy individuals (10 distinct
      brain regions each). Weighted gene coexpression network analysis was used to
      cluster 24 SCA genes into gene coexpression modules in an unsupervised manner.
      The overrepresentation of SCA transcripts in modules identified in the cerebellum
      was assessed. Enrichment analysis was performed to infer the functions and
      molecular pathways of genes in biologically relevant modules. MAIN OUTCOMES AND
      MEASURES: Molecular functions and mechanisms implicating SCA genes, as well as
      lists of relevant coexpressed genes as potential candidates for novel SCA
      causative or modifier genes. RESULTS: Two cerebellar gene coexpression modules
      were statistically enriched in SCA transcripts (P = .021 for the tan module and P
      = 2.87 * 10-5 for the light yellow module) and contained established granule and
      Purkinje cell markers, respectively. One module includes genes involved in the
      ubiquitin-proteasome system and contains SCA genes usually associated with a
      complex phenotype, while the other module encloses many genes important for
      calcium homeostasis and signaling and contains SCA genes associated mostly with
      pure ataxia. CONCLUSIONS AND RELEVANCE: Using normal gene expression in the human
      brain, we identified significant cell types and pathways in SCA pathogenesis. The
      overrepresentation of genes involved in calcium homeostasis and signaling may
      indicate an important target for therapy in the future. Furthermore, the gene
      networks provide new candidate genes for ataxias or novel genes that may be
      critical for cerebellar function.

PMID- 24862035
TI  - Basal cell carcinoma arising in the prostate.

PMID- 24862036
TI  - Fluorescence methods (VistaCam iX proof and DIAGNODent pen) for the detection of
      occlusal carious lesions in teeth recovered from archaeological context.
AB  - Diagnosis of occlusal enamel caries in archaeologically derived collections
      remains a controversial problem because the accumulation of contaminants in
      fissures can interfere with diagnosis. Certain novel light-induced fluorescence
      methods, such as the DIAGNODent pen 2190 (DD) and VistaCam iX Proof (VC), have
      been used to detect dental caries in clinical settings. In this study, the
      abilities of DD and VC to detect initial enamel caries in archaeologically
      derived material is determined and compared with those of other methods (visual
      inspection, X-ray, histology, and micro-CT). Dental material encompassing the
      remains of 58 individuals, including a total of 380 teeth from each of three
      historical periods: modern Islamic (AD 1850-1950), Islamic (AD 600-1200) and late
      Roman (AD 200-400), obtained from two archaeological sites (Terqa and Tell
      Masaikh) located in the Middle Euphrates valley (Syria), were analyzed. VC was
      found to have excellent sensitivity (98), while DD obtained lower sensitivity
      (76) in detecting dental caries in its early stages. The results obtained by VC
      and micro-CT, considered the most reliable imaging technique, were not
      statistically significant (P = 0.3068). By contrast, results obtained by DD and
      micro-CT results, and DD and VC results were statistically significant (P <
      0.0001, P = 0.0015, respectively). However the presence of dirt, stain, calculus,
      and plaque in the pits and fissures of the occlusal surface compromise correct
      diagnosis of caries by VC and DD. Consequently, for teeth recovered from
      archaeological contexts where staining, calculus and plaque are present, the best
      solution remains micro-CT.

PMID- 24862037
TI  - Recurrence of endometrial polyps.
AB  - AIMS: To estimate the recurrence rate of patients with endometrial polyps and to
      evaluate whether the recurrence can be correlated with the histopathologic
      features of the polyp. METHODS: Two hundred and eighty-two women with endometrial
      polyps in both pre- or postmenopausal period and suffering from abnormal uterine
      bleeding or not were treated by resectoscopic surgery in a tertiary university
      hospital and were subsequently followed to check for polyp recurrence. RESULTS:
      Polyp recurrence rate after hysteroscopic surgery and correlation between
      recurrence and main demographic, hysteroscopic and histopathologic
      characteristics were analyzed. During mean +/- SD follow-up period of 26.3 +/-
      19.7 months, the overall recurrence rate was high (13.3%) and did not vary (p =
      NS) with age, parity, weight or other demographic characteristics of the patients
      or with the hysteroscopic appearance. On the contrary, the histopathologic
      features showed significant differences between patients with and without polyp
      recurrence. Recurrence rate was higher (p < 0.001) in women with
      histopathologically hyperplastic polyps without atypia and lower (p < 0.001) in
      women with benign polyps. CONCLUSION: The study shows that after resectoscopic
      polypectomy, the recurrence rate of endometrial polyps is high (13.3%). Moreover,
      the hyperplastic polyps without atypia recur more frequently than benign ones.

PMID- 24862039
TI  - Cerebral and non-cerebral coenurosis in small ruminants.
AB  - Cerebral coenurosis is caused by Coenurus cerebralis, the larval stage of Taenia
      multiceps. The metacestode causes severe lesions in the brain and spinal cord of
      the intermediate host, so-called "gid" or "stagger" disease. Whereas, the non
      cerebral coenurosis caused by Coenurus gaigeri, the larval stage of Taenia
      gaigeri, particularly affects goats. The cyst form of the Taenia gaigeri is found
      in intramuscular and subcutaneous tissues. The difference in the sequence of
      mitochondrial genes of cox1 and nadI and also other variations reported for
      clinical, morphological and pathological aspects in coenurosis lead to the
      hypothesis that there is genetic intraspecific variability within this species,
      such as in other members of the genus Taenia. Nevertheless, it has been shown
      that sheep and goats have been infected by both cerebral and non-cerebral
      coenurosis and it has been suggested that such cerebral and non-cerebral
      metacestodes may belong to different species of Taenia which are host specific
      for these hosts. 

PMID- 24862040
TI  - Antibiotic resistance profile and virulence genes of uropathogenic Escherichia
      coli isolates in relation to phylogeny.
AB  - Escherichia coli (E. coli) strains are the major cause of urinary tract
      infections (UTI) and belong to the large group of extra-intestinal pathogenic E.
      coli. The purposes of this study were to determine the antibiotic resistance
      profile, virulence genes and phylogenetic background of E. coli isolates from UTI
      cases. A total of 137 E. coli isolates were obtained from UTI samples. The
      antimicrobial susceptibility of confirmed isolates was determined by disk
      diffusion method against eight antibiotics. The isolates were examined to
      determine the presence and prevalence of selected virulence genes including iucD,
      sfa/focDE, papEF and hly. ECOR phylo-groups of isolates were determined by
      detection of yjaA and chuA genes and fragment TspE4.C2. The antibiogram results
      showed that 71% of the isolates were resistant to cefazolin, 60.42% to co
      trimoxazole, 54.16% to nalidixic acid, 36.45% to gentamicin, 29.18% to
      ciprofloxacin, 14.58% to cefepime, 6.25% to nitrofurantoin and 0.00% to imipenem.
      Twenty-two antibiotic resistance patterns were observed among the isolates.
      Virulence genotyping of isolates revealed that 58.39% isolates had at least one
      of the four virulence genes. The iucD gene was the most prevalent gene (43.06%).
      The other genes including sfa/focDE, papEF and hly genes were detected in 35.76%,
      18.97% and 2.18% isolates, respectively. Nine combination patterns of the
      virulence genes were detected in isolates. Phylotyping of 137 isolates revealed
      that the isolates fell into A (45.99%), B1 (13.14%), B2 (19.71%) and D (21.16%)
      groups. Phylotyping of multidrug resistant isolates indicated that these isolates
      are mostly in A (60.34%) and D (20.38%) groups. In conclusion, the isolates that
      possessed the iucD, sfa/focDE, papEF and hly virulence genes mostly belonged to A
      and B2 groups, whereas antibiotic resistant isolates were in groups A and D.
      Escherichia coli strains carrying virulence factors and antibiotic resistance are
      distributed in specific phylogenetic background. 

PMID- 24862038
TI  - Runx2 regulates endochondral ossification through control of chondrocyte
      proliferation and differentiation.
AB  - Synthesis of cartilage by chondrocytes is an obligatory step for endochondral
      ossification. Global deletion of the Runx2 gene results in complete failure of
      the ossification process, but the underlying cellular and molecular mechanisms
      are not fully known. Here, we elucidated Runx2 regulatory control distinctive to
      chondrocyte and cartilage tissue by generating Runx2 exon 8 floxed mice. Deletion
      of Runx2 gene in chondrocytes caused failure of endochondral ossification and
      lethality at birth. The limbs of Runx2(DeltaE8/DeltaE8) mice were devoid of
      mature chondrocytes, vasculature, and marrow. We demonstrate that the C-terminus
      of Runx2 drives its biological activity. Importantly, nuclear import and DNA
      binding functions of Runx2 are insufficient for chondrogenesis. Molecular studies
      revealed that despite normal levels of Sox9 and PTHrP, chondrocyte
      differentiation and cartilage growth are disrupted in Runx2(DeltaE8/DeltaE8)
      mice. Loss of Runx2 in chondrocytes also impaired osteoprotegerin-receptor
      activator of NF-kappaB ligand (OPG-RANKL) signaling and chondroclast development.
      Dwarfism observed in Runx2 mutants was associated with the near absence of
      proliferative zone in the growth plates. Finally, we show Runx2 directly
      regulates a unique set of cell cycle genes, Gpr132, Sfn, c-Myb, and Cyclin A1, to
      control proliferative capacity of chondrocyte. Thus, Runx2 is obligatory for both
      proliferation and differentiation of chondrocytes.

PMID- 24862041
TI  - Seroprevalence of bluetongue among domestic ruminants in Northern Kerala, India.
AB  - The objective of the present study is to assess the seroprevalence of bluetongue
      (BT) among domestic ruminants of Northern Kerala. Sera samples from cattle (82),
      goat (40) and sheep (50) collected from districts of Wayanad, Kozhikode and
      Palakkad respectively were tested using competitive enzyme linked immune-sorbent
      assay (cELISA). Out of the 172 samples tested, the overall BT seroprevalence was
      9.3%. There is an increase in prevalence from previous reports which may indicate
      possible outbreaks in future. 

PMID- 24862042
TI  - Severe Plasmodium knowlesi infection with multiorgan involvement in north east
      peninsular Malaysia.
AB  - Plasmodium knowlesi has been recently identified as the "fifth human malaria
      species" following the discovery in Malaysian Borneo of a large focus of this
      simian malaria parasite in humans. Even though it shares microscopic similarities
      with Plasmodium malariae, it may cause severe illness with risk of fatality. We
      describe a case of P. knowlesi infection causing multi-organ failure in a patient
      who was successfully managed due to early recognition of the infection.
      Clinicians in this region should be more aware of the infection as it is not as
      rare as previously thought. This case write up highlight the case of severe
      malaria infection which presented with multi organ involvement which is caused by
      P. knowlesi. 

PMID- 24862044
TI  - Acaricidal activity of alkaloid fractions of Leucas indica Spreng against
      Rhipicephalus (Boophilus) annulatus tick.
AB  - The acaricidal activity from alkaloid and non-alkaloid fractions of Leucas indica
      were studied against Rhipicephalus (Boophilus) annulatus tick using adult
      immersion test under laboratory conditions. For this purpose, the engorged female
      R.(B.) annulatus tick were exposed to two fold serial dilutions of alkaloid
      extract (50 mg/ml, 25 mg/ml, 12.5 mg/ml, 6 mg/ml and 3 mg/ml) using 'dipping
      method' in vitro. The efficacy was assessed by measuring the percentage of adult
      mortality, inhibition of fecundity and hatching rate. The alkaloid fraction of
      the extract produced concentration dependent delayed adult tick mortality. The
      extract at a concentration of 50 mg/ml demonstrated 66.67 per cent mortality and
      55.16 per cent inhibition of fecundity. Nicotine was identified as one of the
      compounds of alkaloid fraction. However, it did not reveal any acaricidal
      activity when tested in vitro at concentrations ranging from 62.5-1000 MUg/mL.
      Hence, the acaricidal action of L. indica is not due to nicotine. Non alkaloid
      fraction also did not reveal any acaricidal effects against R. (B.) annulatus
      tick. 

PMID- 24862045
TI  - Gastrointestinal parasites of birds in zoological gardens in south-west Nigeria.
AB  - Infections with gastrointestinal parasites are a major health issue in captive
      birds. However, prevalence data of gastrointestinal parasites of birds in
      zoological gardens in Nigeria are scarce. This study was carried out to establish
      the gastrointestinal parasite profile of birds kept in zoological gardens in the
      University of Ibadan, Obafemi Awolowo University, University of Ilorin,
      University of Lagos and Federal University of Agriculture Abeokuta, all in south
      west Nigeria. A total of 178 fecal samples from 83 birds (14 species in eight
      orders) were examined using three techniques; Feacal sedimentation using ethyl
      acetate, McMaster Egg Counting Technique and Petri Dish-Filter Paper Slant
      culture technique (modified Harada-Mori Technique). A total of 39(21.9%) of the
      178 samples were infected. The highest prevalence (100%) of infection was
      recorded in Unilag zoo and a total of five species of parasites including two
      protozoans (coccidian and Balantidium spp.); and three nematodes Capillaria spp.,
      Ascaris spp. and Strongyloides spp.) were recorded with Capillaria spp. (14.1%)
      as the most prevalent gastrointestinal parasite. Mixed infections were found in
      18(10.1%) samples. Strongyloides larvae were observed in 6(3.4%) samples. All
      Anseriformes were infected but the Struthioniformes had the highest infection
      rate. The geometric mean intensity of eggs ranged from 101.98 +/- 10.36 to 63.00
      +/- 16.67 epg and oocyst counts ranged from 332.47 +/- 16.67 to 297.89 +/- 20.41
      opg. Balantidium cyst count was 324.04 +/- 25.00. Count of oocyst of coccidian
      species was significantly higher in all the zoos. The feacal culture yielded
      Strongyloides species. Regular deworming and hygienic measures are necessary to
      prevent gastrointestinal infections in captive birds. So also, improved funding
      and management are necessary to ensure sustainability of Nigerian zoological
      gardens.

PMID- 24862043
TI  - Comparison of nested and ELISA based polymerase chain reaction assays for
      detecting Chlamydia trachomatis in pregnant women with preterm complications.
AB  - Identification of pregnant women infected with Chlamydia trachomatis is essential
      to allow early antibiotic treatment in order to prevent adverse pregnancy
      outcomes. In this study, two nucleic acid amplification tests (NAAT) namely
      nested PCR (BioSewoom, Korea) and Amplicor CT/NG (Roche Diagnostic, USA) were
      evaluated in terms of sensitivity and specificity for the detection of C.
      trachomatis DNA in pregnant women with preterm complications. A cross-sectional
      study was carried out in two public hospitals in Southern Selangor, Malaysia.
      Endocervical swabs obtained were subjected to DNA amplification using nested PCR
      (BioSewoom, Korea) and Amplicor CT/NG (Roche Diagnostic, USA). A total of 83
      endocervical swabs obtained from pregnant women of less than 37 weeks gestation
      and presented with preterm complications were subjected to chlamydial DNA
      detection using both assays. The study shows that Amplicor CT/NG assay is more
      effective in the detection of C. trachomatis DNA from endocervical swabs compared
      to Biosewoom nested PCR kit. Agreement between the two assays were poor
      (kappa=0.094) with nested PCR showing a low sensitivity of 10.81% and a 97.83%
      specificity when compared to Amplicor CT/NG. The results obtained indicated that
      BioSewoom nested PCR was less sensitive than Amplicor CT/ NG for detecting C.
      trachomatis in endocervical specimens and that another more reliable test is
      required for confirmatory result. 

PMID- 24862046
TI  - Structural analysis of raw and commercial farm edible bird nests.
AB  - Edible bird nests (EBNs) are consumed worldwide for various health benefits. EBNs
      are nests built from the saliva of swiftlets of Aerodramus species. The global
      market for EBNs is on the rise, especially from Hong Kong and mainland China. In
      the past, EBNs were harvested mainly from natural caves; however in the recent
      years, there has been a rapid growth of swiftlet farming. Little is known about
      the actual composition of EBNs except for protein, carbohydrate, ash and lipid
      contents, amino acids, vitamins and macro/ micronutrients. Besides the
      biochemical components of EBNs, are there any other structures that are
      associated with EBNs? This paper reports on the structural analysis of raw
      unprocessed farm and processed commercial EBNs. The raw EBNs were purchased from
      swiftlet farms in five locations in Peninsula Malaysia: Kuala Sanglang (Perlis; 6
      degrees  16' 0"N, 100 degrees  12' 0"E), Pantai Remis (Perak; 4o 27' 0" N, 100o
      38' 0" E), Kluang (Johor; 02o 012 303N 103o 192 583E), Kajang (Selangor; 2o 59'
      0"N, 101o 47' 0"E) and Kota Bharu (Kelantan; 6o 8' 0"N, 102o 15' 0"E). The
      commercial nests were purchased from five different Chinese traditional medicinal
      shops (Companies A-E). A portion of each EBN was randomly broken into small
      fragments, attached to carbon tape and coated with gold and palladium particles
      for examination and photography under a scanning electron microscope. Structural
      analysis revealed the presence of mites, fungi, bacteria and feather strands on
      both the raw and commercial nests. Mite eggshells and faecal pellets, and body
      parts of other arthropods were seen only in the raw nests. The commercial nests
      had a variety of unidentified structures and substances coated on the nests'
      surfaces that were not found on the raw nests. The presence of these contaminants
      may jeopardise the quality of EBNs and pose health risks to consumers. Further
      identification of the mites and their allergens, fungi and bacteria are on-going
      and will be reported separately. 

PMID- 24862047
TI  - Prevalence and transmission dynamics of Schistosoma haematobium infection in a
      rural community of southwestern Ebonyi State, Nigeria.
AB  - A twelve-month epidemio-ecological study on the prevalence, infection intensity,
      water contact and vector aspects of urinary schistosomiasis was conducted in a
      rural community of south-west Ebonyi State, Nigeria, using standard procedures,
      and involving 894 individuals (527, 58.9% males; and 367, 41.1% females). An
      overall community prevalence (15.3%) was established with more males (20.7%) than
      females (7.6%) being significantly positive for both micro-and macro-haematuria
      (chi2 = 0.806; df = 1, p < 0.05). Intensity of infection was generally of the
      light category (< 100 eggs/10 ml urine) with more infected males (n = 95, 87.2%)
      than infected females (n = 15, 53.6%). Correlation analysis showed no linear
      relationship between prevalence and intensity of infection. Individuals aged 16
      20 years dominated interschool/intervillage infection profile (range 13.2-50%)
      while participants in 6-10 years age bracket recorded the lowest infection rates
      (range 2.8-5.0%). Age-related difference in prevalence was not significant (chi2
      = 1.80; df = 2, p > 0.05). A total of 2877 ova of Schistosoma haematobium were
      recovered providing an overall mean egg burden of 21 +/- 7 eggs/10 ml urine per
      infected person. Age-related infection intensity was similarly of the light
      category involving 80.3% of infected persons. Bulinus globosus (n = 308) was
      identified as the vector of the parasite with 20.1% snails found to be shedding
      cercariae. Monthly and seasonal infection rates in snails were season-dependent
      and peaking in May (35.5%). Participants aged 13-15 years accounted for 25.1% of
      total water contacts (n = 9938) whereas individuals aged 6-9 years accounted for
      only 9.6% contacts. The most performed water contact activity was bathing
      (33.3%), followed by washing of clothes (25.7%). Correlation analysis indicated
      that village of residence, age and cumulative water contacts were significant
      correlates of possible S. haematobium infection.

PMID- 24862048
TI  - Antitrypanosomal screening and cytotoxic effects of selected medicinal plants.
AB  - Trypanosoma evansi, the causative agent of "surra", infects many species of wild
      and domestic animals worldwide. In the current study, the aqueous and ethanolic
      extracts of six medicinal plants, namely, Aquilaria malaccensis, Derris
      elliptica, Garcinia hombroniana, Goniothalamus umbrosus, Nigella sativa, and
      Strobilanthes crispus were screened in vitro for activity against T. evansi. The
      cytotoxic activity of the extracts was evaluated on green monkey kidney (Vero)
      cells using MTT-cell proliferation assay. The median inhibitory concentrations
      (IC50) of the extracts ranged between 2.30 and 800.97 MUg/ml and the median
      cytotoxic concentrations (CC50) ranged between 29.10 MUg/ml and 14.53 mg/ml. The
      aqueous extract of G. hombroniana exhibited the highest selectivity index (SI)
      value of 616.36, followed by A. malaccensis aqueous extract (47.38).
      Phytochemical screening of the G. hombroniana aqueous extract revealed the
      presence of flavonoids, phenols, tannins, and saponins. It is demonstrated here
      that the aqueous extract of G. hombroniana has potential antitrypanosomal
      activity with a high SI, and may be considered as a potential source for the
      development of new antitrypanosomal compounds. 

PMID- 24862049
TI  - Purification and characterization of keratinase from feather degrading bacterium
      useful for mosquito control--a new report.
AB  - Every day, food processing industries release wastes, which are environmental
      menance. Chicken feathers have been discarded in bulk as waste from poultry
      industries, globally. Degrading these wastes, as unused disposals, without
      acquiring any additional benefits has led to an idea to develop a new technology.
      We have reported earlier that Bacillus thuringiensis serovar israelensis (Bti)
      can be used for biodegradation of feather waste for biopesticide production. In
      the present study, purification and characterization of keratinase from feather
      degrading bacterium (Bti) is reported. Protein precipitate obtained at Ammonium
      sulphate saturation at 60% level and Sephacryl S-200 column chromatography
      resulted in 2.3 and 11.68 fold purification of the enzyme respectively. The
      purity was revealed in SDS-PAGE by a single band of molecular weight of 40 kDa
      and it was characterized. The optimum pH of the enzyme shifted to a more neutral
      range (6.0-8.0) with the highest activity (7.0). The optimum temperature of the
      reaction was determined to be 30oC. The keratinase enzyme retained 51% residual
      activity (303 U/mg protein) at 70oC (60 min) and the half-lives of the enzyme
      were 130 minutes at 40oC, 90 min at 50oC and of 60 min at 70oC, respectively.
      Keratinase activity was enhanced by calcium and magnesium ions while EDTA, PMSF,
      beta- mercaptoethanol and manganese inhibited the activity. This is the first
      report investigating the keratinase from Bti degraded chicken feathers for the
      bio-synthesis of mosquitocidal toxins. 

PMID- 24862050
TI  - Diagnosis of subclinical equine theileriosis in center of Iran using
      parasitological and molecular methods.
AB  - A total of 105 blood samples from healthy horses from different stables in Yazd
      province, center of Iran, were examined for the presence of Theileria equi
      infection using parasitological and molecular methods. Out of the 105 samples,
      the parasitological method detected T. equi infection in 5 (4.76%) cases while
      the PCR method gave 24 (22.86%) positive results. Age, gender and breed were not
      determined as risk factors for T. equi infection in this study. Since blood
      samples were taken from healthy animals, this implies that 22.86% of horses had
      subclinical theileriosis in the current study. In conclusion, this study
      demonstrated that T. equi is present in horses in the center of Iran. Despite the
      healthy appearance of horses, these carrier animals can transmit the parasites to
      ticks and are a potential continuous source for maintaining and disseminating the
      organisms to the horse population. We concluded that it is important to make
      further studies on definitive host and vectors in the respective areas. 

PMID- 24862051
TI  - The emerging threat of schistosomiasis spread in Pakistan.
AB  - Schistosomiasis is among the thirteen neglected tropical diseases of the world.
      While prevalent in a number of countries, it has only rarely been reported in
      Pakistan. Here we report a 25 year old male who acquired the infection during
      travel to Malawi and presented with haematuria and dysuria. He was successfully
      treated with praziquantel. The possibility of schistosomiasis becoming endemic in
      the country is discussed. A number of risk factors are present including dams,
      irrigation, increased travel and geographical proximity to endemic countries. The
      local presence of at least one snail species of potential hosts for Schistosoma
      mansoni is confirmed. We see that schistosomiasis endemicity is a possible threat
      in Pakistan. Solutions to prevent this include reducing travel to endemic areas,
      prompt recognition and treatment of cases, and health education. 

PMID- 24862052
TI  - Genotypic detection and evaluation of the removal efficiency of Giardia
      duodenalis at municipal wastewater treatment plants in Northern South Africa.
AB  - Over the past decade, Giardia duodenalis has increasingly been implicated in
      diarrheal outbreaks and water and wastewater have been recognized as important
      vehicles for diseases. Although studies have reported the occurrence of these
      parasites in developed countries, their occurrence in water and wastewater bodies
      in these countries including South Africa has not been thoroughly investigated.
      In the present study, wastewater samples from 6 different sewage treatment plants
      in the Vhembe District were collected for a period of 12 months. The samples were
      concentrated and tested for the presence of G. duodenalis using both microscopy
      and polymerase chain reaction methods targeting the tpi gene. Of the 79
      wastewater samples tested, 25 (31.65%) were positive. Of these, 15 (60%) were
      assemblage A, while 8 (32%) were assemblage B and 2 samples (8%) were positive
      for both genogroups. Assemblage A was more common in February 2010 while
      assemblage B showed two peaks in December-January and March-April and was not
      detected in May 2010. The general removal rate was 40% for plants using
      biological filters and 20% for plants using activated sludge. The present study
      has shown that Giardia assemblage A is more common in sewage treatment plants in
      the Vhembe District, but the removal efficiency was low. This represents a public
      health hazard since these organisms might contaminate drinking water sources.
      Therefore action needs to be taken for the design of more effective procedures or
      methods for the removal of these parasites from the environment in order to avoid
      potential outbreaks. 

PMID- 24862054
TI  - Comparative antioxidant and antiplasmodial activities of 11-O-galloylbergenin and
      bergenin isolated from Bergenia ligulata.
AB  - In the present study, the antioxidant and antiplasmodial activities of bergenin
      was compared with its natural derivative 11-O-galloylbergenin for the first time.
      Both compounds were isolated from Bergenia ligulata. 11-O-galloylbergenin was
      found to be very active in in-vitro antioxidant assay as compared to bergenin,
      which was found to be almost inactive. The EC50 values of 11-O-galloylbergenin
      were 7.45+/-0.2 MUg/mL and 5.39+/-0.28 MUg/mL in DPPH antioxidant assay and
      reducing power assay respectively, while IC50 value for antiplasmodial assay of
      both compounds were less than 2.5 MUM. Interestingly, in the total antioxidant
      phosphomolybdate assay, 11-O-galloylbergenin was found more potent (CAHT:
      940.04+/-115.30) as compared to alpha-tocopherol (CAHT: 552.4+/-27.91). 

PMID- 24862053
TI  - Bacteria as a source of oviposition attractant for Aedes aegypti mosquitoes.
AB  - Since a safe and effective mass vaccination program against dengue fever is not
      presently available, a good way to prevent and control dengue outbreaks depends
      mainly on controlling the mosquito vectors. Aedes aegypti mosquito populations
      can be monitored and reduced by using ovitraps baited with organic infusions. A
      series of laboratory experiments were conducted which demonstrated that the
      bacteria in bamboo leaf infusion produce volatile attractants and contact
      chemical stimulants attractive to the female mosquitoes. The results showed that
      the female mosquitoes laid most of their eggs (59.9 +/- 8.1 vs 2.9 +/- 2.8 eggs,
      P<0.001) in bamboo leaf infusions when compared to distilled water. When the
      fresh infusion was filtered with a 0.45 MUm filter membrane, the female
      mosquitoes laid significantly more eggs (64.1 +/- 6.6 vs 4.9 +/- 2.6 eggs,
      P<0.001) in unfiltered infusion. However when a 0.8 MUm filter membrane was used,
      the female laid significantly more eggs (62.0 +/- 4.3 vs 10.1 +/- 7.8 eggs,
      P<0.001) in filtrate compared to a solution containing the residue. We also found
      that a mixture of bacteria isolated from bamboo leaf infusion serve as potent
      oviposition stimulants for gravid Aedes mosquitoes. Aedes aegypti laid
      significantly more eggs (63.3 +/- 6.5 vs 3.1 +/- 2.4 eggs, P<0.001) in bacteria
      suspension compared to sterile R2A medium. Our results suggest microbial activity
      has a role in the production of odorants that mediate the oviposition response of
      gravid mosquitoes.

PMID- 24862055
TI  - Effect of community participation on household environment to mitigate dengue
      transmission in Thailand.
AB  - Due to the absence of dengue vaccination, vector control is the only measure to
      prevent dengue outbreaks. The key element of dengue prevention is to eliminate
      vector habitats. Clean household environment, preventive behaviors of household
      members and community participation in dengue prevention and control are key
      successful elements. This study aimed to investigate the associations between
      environmental factors, dengue knowledge, perception and preventive behaviors of
      household and collaboration of community members and household risk of dengue by
      using mixed methods. One dengue epidemic province was selected from each region
      of Thailand including Bangkok. Two districts, one from the highest and another
      from the lowest dengue incidence areas, were selected from those provinces. The
      household leaders, community members, and local authorities in highest dengue
      incidence areas were interviewed by using questionnaire and through group
      interviews. The environment of each selected household was observed. Of 4,561
      households, 194 were reported having dengue case(s) in the past year and that
      outdoor solid waste disposal significantly influenced household risk of dengue
      (OR=1.62; 95% CI=1.16-2.29). In contrast, having gardening areas reduced dengue
      risk at household level by 32%. High level of community participation in dengue
      prevention and control in uninfected areas and the information from local
      authorities and community members reconfirmed that community participation was
      the key factor against dengue outbreaks. Sustainable process of encouraging
      community members to eliminate vector breeding sites such as outdoor solid waste
      disposal is likely to lead to an achievement in dengue prevention and control. 

PMID- 24862056
TI  - Current insecticide susceptibility status of Malaysian Anopheles maculatus
      Theobald to malathion, permethrin, DDT and deltamethrin.
AB  - Chemical insecticides are still considered as important control agents for
      malaria vector control. However, prolonged use of these chemicals may select
      mosquito vectors for resistance. In this study, susceptibility status of adult
      Anopheles maculatus collected from 9 localities in peninsular Malaysia, viz.,
      Jeli, Temerloh, Pos Banun, Senderut, Jeram Kedah, Segamat, Kota Tinggi, Kluang
      and Pos Lenjang were determined using the standard WHO bioassay method in which
      the adult mosquitoes were exposed to standard insecticide impregnated papers
      malathion, permethrin, DDT and deltamethrin--at pre-determined diagnostic dosage.
      Deltamethrin was most effective insecticide among the four insecticides tested,
      with the LT50 of 29.53 min, compared to malathion (31.67 min), DDT (47.76 min)
      and permethrin (48.01 min). The effect of all insecticides on the laboratory
      strain was greater (with all insecticides demonstrated LT50 < 1 hour) than the
      field strains (deltamethrin 32.7, malathion 53.0, permethrin 62.0, DDT 67.4 min).
      An. maculatus exhibited low degree of resistance to all test insecticides,
      indicating that these chemical insecticides are still effective in the control of
      malaria vector.

PMID- 24862058
TI  - Virulence genotyping of Escherichia coli isolates from diarrheic and urinary
      tract infections in relation to phylogeny in southeast of Iran.
AB  - The purpose of this study was to determine the prevalence of virulence genes and
      phylogenetic groups/subgroups of Escherichia coli (E. coli) isolates from
      diarrheic and urinary tract infections (UTI) cases in Rigan area, southeast of
      Iran. One hundred thirty five E. coli were isolated from diarrheic (90 isolates)
      and urinary tract infections (45 isolates) samples. The confirmed isolates were
      examined to detect the phylogenetic group/subgroups and a selection of virulence
      genes including iucD, sfa/focDE, afaIBC, papEF, hly, cnfI and cdtI by PCR. The
      examined isolates belonged to four phylogenetic groups A (42.2%), B1 (14.1%), B2
      (10.4%), and D (33.3%). Among 135 tested bacteria, 62.22% of diarrheic and 30.37%
      of UTI isolates had at least one of the virulence genes. In the diarrheic
      isolates iucD (47.77%) was the most prevalent gene. The other genes including
      sfa/focDE, afaIBC, papEF and cnfI/cdtI genes were detected in 15, 13, 11 and one
      diarrheic isolates respectively. None of the diarrheic isolates were positive for
      hly gene. Out of 45 UTI isolates 28.88% were positive for iucD, 13.33% for cnfI,
      11.11% for afaIBC, 11.11% for papEF, 6.66% for sfa/focDE and 4.44% for cdtI
      genes. Several combination patterns of the virulence genes were detected in
      diarrheic and UTI isolates. In conclusion, the prevalence of virulence genes in
      diarrheic and UTI isolates differ according to phylogenetic groups, although B2
      and D phylotypes have an accumulation of virulence associated genes. 

PMID- 24862057
TI  - Influence of container design on predation rate of potential biocontrol agent,
      Toxorhynchites splendens (Diptera: Culicidae) against dengue vector.
AB  - Toxorhynchites splendens larvae are a natural predator of dengue vector mosquito
      larvae, Aedes albopictus. This study was carried out to evaluate the predation
      rate of Tx. splendens third instar larvae on Ae. albopictus larvae in 24 h. Each
      predator was offered prey at a density between 10 to 50 individuals. Predation
      rate of Tx. splendens were also tested with two manipulated factors; various
      types of container and different water volumes. The experiment was evaluated in
      man-made containers (tin cans, plastic drinking glasses and rubber tires) and
      natural container (bamboo stumps) which were filled with different water volumes
      (full, half full, 1/4 full, and 1/8 full). The prey density and the
      characteristics of the container were found as significant factors which
      influence the predation rate of Tx. splendens. The predator consumed
      significantly more prey at higher prey densities (40 and 50 preys) compared to
      the lowest density (10 preys) (F=3.935, df=4, p=0.008). The results showed
      significantly higher consumption in horizontal shaped container of rubber tire
      than in vertical shape of bamboo stumps (F=3.100, df=3, p=0.029). However, the
      water volume had no significant effect on predation rate of Tx. splendens
      (F=1.736, df=3, p=0.162). We generally suggest that Tx. splendens is best to be
      released in discarded tires or any other containers with horizontal shape design
      with wide opening since Tx. splendens can become more effective in searching prey
      in this type of container design. This predator is also a suitable biocontrol
      candidates to be introduced either in wet and dry seasons in Malaysia. 

PMID- 24862059
TI  - Molecular identification of Sarcocystis hominis in native cattle of central Iran:
      a case report.
AB  - Sarcocystis spp. are two-host protozoan parasites belonging to the phylum
      Apicomplexa. Among different known species of Sarcocystis in cattle, only
      Sarcocystis hominis is important from the public health viewpoint, because of its
      zoonotic characteristics. This study presents the first molecular identification
      of S. hominis in native cattle in central Iran. A sample of diaphragm muscle from
      a 6-year-old native cow slaughtered at Yazd Slaughterhouse, Yazd, central Iran,
      was collected in May 2013. DNA extraction was performed, using the salting-out
      method. DNA purification and precipitation were performed consecutively. The
      amplicon and digestion results were analyzed using agarose gel electrophoresis. A
      PCR product with 926 bp in length was obtained after amplification, and 376 bp
      and 550 bp in length after digestion that identified S. hominis. To the best of
      our knowledge, this study is the first of its kind to be reported from Iran. 

PMID- 24862060
TI  - An unusual cause of chronic diarrhoea.
AB  - We report a patient presenting with chronic diarrhoea of unidentified etiology.
      Laboratory results showed microcytic anemia, peripheral eosinophilia with
      negative results of stool sample smears and stool concentration technique.
      Ancylostoma duodenale was found in the caecum and terminal ileum during
      colonoscopy. The patient was treated with a 3-day course of 400 mg albendazole
      and iron supplement. The diarrhoea disappeared shortly after treatment.
      Physicians particularly in tropical areas should be aware of hookworms as
      causative agents of chronic diarrhoea and it may be found in the large intestine.

PMID- 24862061
TI  - Tetrahedral-mesh-based computational human phantom for fast Monte Carlo dose
      calculations.
AB  - Although polygonal-surface computational human phantoms can address several
      critical limitations of conventional voxel phantoms, their Monte Carlo simulation
      speeds are much slower than those of voxel phantoms. In this study, we sought to
      overcome this problem by developing a new type of computational human phantom, a
      tetrahedral mesh phantom, by converting a polygonal surface phantom to a
      tetrahedral mesh geometry. The constructed phantom was implemented in the Geant4
      Monte Carlo code to calculate organ doses as well as to measure computation
      speed, the values were then compared with those for the original polygonal
      surface phantom. It was found that using the tetrahedral mesh phantom
      significantly improved the computation speed by factors of between 150 and 832
      considering all of the particles and simulated energies other than the low-energy
      neutrons (0.01 and 1 MeV), for which the improvement was less significant (17.2
      and 8.8 times, respectively). 

PMID- 24862062
TI  - Cyclodepsipeptides from the ascocarps and insect-body portions of fungus
      Cordyceps cicadae.
AB  - A new cyclodepsipeptide cordycecin A (1), together with four known ones
      beauvericin E (2), beauvericin J (3), beauvericin (4), and beauvericin A (5) was
      isolated from the ascocarps and insect-body portions of fungus Cordyceps cicadae.
      Their structures were identified by NMR and MS analyses. The absolute
      configuration of 1 was confirmed by crystal X-ray diffraction. Compounds 2-5
      exhibited a significant inhibitory effect on HepG2 and HepG2/ADM cells with IC50
      values ranging from 2.40+/-0.37 to 14.48+/-1.68 MUM. Interestingly, compounds 3-5
      showed cytotoxic activity against multiple drug resistant HepG2 cell line
      (HepG2/ADM) with IC50 value 25-fold more sensitive to doxorubicin.

PMID- 24862063
TI  - Two new sesquiterpenes from Artemisia sieversiana.
AB  - Two new sesquiterpenes, together with 32 known compounds(3-34), were isolated
      from Artemisia sieversiana Ehrhart ex willd. and the compounds 3-21 were isolated
      from this plant for the first time. The new compounds were elucidated as
      2alpha,9alpha-dihydroxymuurol-3(4)-en-12-oic acid (1) and 13alpha-methyl
      (5alphaH,6alphaH,7alphaH,8alphaH)-austricin 8-O-beta-D-glucopyranoside (2),
      respectively. The structural identification of these compounds was mainly
      achieved by spectroscopic methods including 1D and 2D NMR techniques, and the
      structure of compound 1 was confirmed by a single crystal X-ray diffraction
      experiment. Compounds 1-2 were evaluated for cytotoxic activity in vitro against
      MCF-7, NCI-H460 and Hep-G2 cell lines, respectively. 

PMID- 24862064
TI  - Role of herbal bioactives as a potential bioavailability enhancer for Active
      Pharmaceutical Ingredients.
AB  - The current review emphasizes on the herbal bioenhancers which themselves do not
      possess inherent pharmacological activity of their own but when co-administered
      with Active Pharmaceutical Ingredients (API), enhances their bioavailability and
      efficacy. Herbal bioenhancers play a crucial role in enhancing the
      bioavailability and bioefficacy of different classes of drugs, such as
      antihypertensives, anticancer, antiviral, antitubercular and antifungal drugs at
      low doses. This paper highlights various natural compounds that can be utilized
      as an efficient bioenhancer. Several herbal compounds including piperine,
      quercetin, genistein, naringin, sinomenine, curcumin, and glycyrrhizin have
      demonstrated capability to improve the pharmacokinetic parameters of several
      potent API. This article also focuses on various United States patents on herbal
      bioenhancers, which has proved to be beneficial in improving oral absorption of
      nutraceuticals like vitamins, minerals, amino acids and certain herbal compounds.
      The present paper also describes proposed mechanism of action, which mainly
      includes absorption process, drug metabolism, and action on drug target. The
      herbal bioenhancers are easily available, safe, free from side effects, minimizes
      drug toxicity, shortens the duration of treatment, lowers the drug resistance
      problems and minimizes the cost of treatment. Inspite of the fact that herbal
      bioenhancers provide an innovative concept for enhancing the bioavailability of
      several potent drugs, there are numerous bioenhancers of herbal origin that are
      yet to be explored in several vital areas. These bioenhancers must also be
      implied to enhance the bioavailability and bioefficacy through routes other than
      the oral route of drug delivery. There is a vast array of unexploited plants
      which can be investigated for their drug bioenhancing potency. The toxicity
      profiles of these herbal bioenhancers must not be overlooked. Researches must be
      carried out to solve these issues and to deliver a safe and effective dose of
      drugs to attain desired pharmacological response. 

PMID- 24862065
TI  - Chemical constituents from the linseed meal.
AB  - One megastigmane derivative 1, one methyl jasmonate glycoside derivative 2, and
      two C-28 steroids with 3beta,5beta-cis-dihydroxyl conformation 3 and 4, together
      with eight known compounds 5-12 were isolated from the 70% ethanol extract of
      linseed meal (Linum usitatissimum L). Structures of 1-4 were elucidated by
      spectroscopic methods including NMR, HRESIMS, and Mo2(OAc)4-induced CD. The
      absolute configuration of 1 and 3 was determined by observing their induced
      circular dichroism after addition of Mo2(OAc)4 in DMSO. The absolute
      configuration of 2 was determined by NOESY experiment together with
      conformational analysis. The structure of 4a was corrected as 4 by an extensive
      analysis of its 1D and 2D NMR, in combination with the Mo2(OAc)4-induced CD in
      DMSO. The effect of all the isolates on nitric oxide (NO) generation by
      stimulated macrophages was evaluated, and none of them showed active. 

PMID- 24862066
TI  - Antileishmanial activity evaluation of adunchalcone, a new prenylated
      dihydrochalcone from Piper aduncum L.
AB  - Bioactivity-guided fractionation of EtOH extract from the leaves of Piper aduncum
      L. (Piperaceae) afforded a new dihydrochalcone, named adunchalcone. Its structure
      was elucidated on the basis of their spectroscopic data, primarily NMR and MS.
      Adunchalcone was evaluated against promastigote forms of Leishmania (L.)
      amazonensis, L. (V.) braziliensis, L. (V.) shawi, and L. (L.) chagasi and
      displayed 50% effective concentrations (EC50) of 11.03, 26.70, and 11.26 MUM, as
      well as selective indexes of 4.86, 2.01, 4.76 and 0.50, respectively. This
      compound was also tested against intracellular forms of L. (L.) amazonensis,
      displaying weak activity, in comparison to reference drug amphotericin B.
      However, despite reduced effect of adunchalcone against amastigotes of L. (L.)
      amazonensis, this work opens the perspective to use this particular molecule as a
      scaffold for the design of novel and selective drug candidates for neglected
      diseases, mainly leishmaniasis.

PMID- 24862067
TI  - Cytotoxic effect of triterpenoids from the root bark of Hibiscus syriacus.
AB  - In this study, 4 new triterpenoids-3beta- acetoxy-olean-11-en,28,13beta-olide
      (1), 3beta- acetoxy-11alpha,12alpha-epoxy-olean-28,13beta-olide (2), 19alpha-epi
      betulin (3), and 20, 28-epoxy-17beta,19beta-lupan-3beta-ol (4)-and 12 known
      compounds, were isolated from the root bark of Hibiscus syriacus L. by using
      acetone extraction. Their structures were characterized by extensive
      spectroscopic analysis. To investigate cytotoxicity, A549 human lung cancer cells
      were exposed to the extract and the compounds identified from it. Significantly
      reduced cell viability was observed with betulin-3-caffeate (12) (IC50, 4.3 MUM).
      The results of this study indicate that betulin-3-caffeate (12) identified from
      H. syriacus L. may warrant further investigation for potential as anticancer
      therapies.

PMID- 24862068
TI  - Gradient elution mode for the troubleshooting of matrix effect on the
      determination of G004 in different tissues by LC-MS/MS.
AB  - A steep gradient elution mode was applied to reduce the risk of matrix effect
      (ME) for the determination of G004, a novel sulfonylurea hypoglycemic drug, in a
      tissue distribution study by LC-MS/MS. The mass spectra of the total-ion-current
      chromatograms combined with the post-column infusion traces enabled the 'unseen'
      interfering species to be directly detected, and ensured that the chromatography
      conditions and sample preparation method were adequate to overcome the ME.
      According to this, a steep gradient elution mode was designed to overcome the
      intense ME from different tissues. The analysis was performed by monitoring the
      transitions m/z 558.1 -> 419.0 for G004 and m/z 489.3 -> 364.1 for glimepiride
      used as the internal standard. Calibration curves recovered over a range from 0.1
      to 10000 ng/mL for seven different tissues. Sex-related difference was found in
      the tissue distribution. The drug levels in the tissues of female rats were about
      two to three times higher than those in male counterparts. The highest level was
      observed in liver, then in kidney, heart, pancreas, lung and spleen, but no G004
      was detected in brain. G004 was slowly eliminated from female rats compared with
      male rats. There was no long-term accumulation of G004 in male or female rat
      tissues.

PMID- 24862069
TI  - A data driven method for estimation of B(avail) and appK(D) using a single
      injection protocol with [11C]raclopride in the mouse.
AB  - PURPOSE: The partial saturation approach (PSA) is a simple, single injection
      experimental protocol that will estimate both B(avail) and appK(D) without the
      use of blood sampling. This makes it ideal for use in longitudinal studies of
      neurodegenerative diseases in the rodent. The aim of this study was to increase
      the range and applicability of the PSA by developing a data driven strategy for
      determining reliable regional estimates of receptor density (B(avail)) and in
      vivo affinity (1/appK(D)), and validate the strategy using a simulation model.
      METHODS: The data driven method uses a time window guided by the dynamic
      equilibrium state of the system as opposed to using a static time window. To test
      the method, simulations of partial saturation experiments were generated and
      validated against experimental data. The experimental conditions simulated
      included a range of receptor occupancy levels and three different B(avail) and
      appK(D) values to mimic diseases states. Also the effect of using a reference
      region and typical PET noise on the stability and accuracy of the estimates was
      investigated. RESULTS: The investigations showed that the parameter estimates in
      a simulated healthy mouse, using the data driven method were within 10+/-30% of
      the simulated input for the range of occupancy levels simulated. Throughout all
      experimental conditions simulated, the accuracy and robustness of the estimates
      using the data driven method were much improved upon the typical method of using
      a static time window, especially at low receptor occupancy levels. Introducing a
      reference region caused a bias of approximately 10% over the range of occupancy
      levels. CONCLUSIONS: Based on extensive simulated experimental conditions, it was
      shown the data driven method provides accurate and precise estimates of B(avail)
      and appK(D) for a broader range of conditions compared to the original method.

PMID- 24862070
TI  - Anatomical correlations of the international 10-20 sensor placement system in
      infants.
AB  - Developmental research, as well as paediatric clinical activity crucially depends
      on non-invasive and painless brain recording techniques, such as
      electroencephalography (EEG), and near infrared spectroscopy (NIRS). However,
      both of these techniques measure cortical activity from the scalp without precise
      knowledge of the recorded cerebral structures. An accurate and reliable mapping
      between external anatomical landmarks and internal cerebral structures is
      therefore fundamental to localise brain sources in a non-invasive way. Here,
      using MRI, we examined the relations between the 10-20 sensor placement system
      and cerebral structures in 16 infants (3-17 weeks post-term). We provided an
      infant template parcelled in 94 regions on which we reported the variability of
      sensors locations, concurrently with the anatomical variability of six main
      cortical sulci (superior and inferior frontal sulcus, central sulcus, sylvian
      fissure, superior temporal sulcus, and intraparietal sulcus) and of the distances
      between the sensors and important cortical landmarks across these infants. The
      main difference between infants and adults was observed for the channels O1-O2,
      T5-T6, which projected over lower structures than in adults. We did not find any
      asymmetry in the distances between the scalp and the brain envelope. However,
      because of the Yakovlean torque pushing dorsally and frontally the right sylvian
      fissure, P3-P4 were not at the same distance from the posterior end of this
      structure. This study should help to refine hypotheses on functional cognitive
      development by providing an accurate description of the localization of
      standardised channels relative to infants' brain structures. Template and atlas
      are publicly available on our Web site
      (http://www.unicog.org/pm/pmwiki.php/Site/InfantTemplate). 

PMID- 24862072
TI  - Patterns of response to visual scenes are linked to the low-level properties of
      the image.
AB  - Scene-selective regions in the brain play an important role in the way that we
      navigate through our visual environment. However, the principles that govern the
      organization of these regions are not fully understood. For example, it is not
      clear whether patterns of response in scene-selective regions are linked to high
      level semantic category or to low-level spatial structure in scenes. To address
      this issue, we used multivariate pattern analysis with fMRI to compare patterns
      of response to different categories of scenes. Although we found distinct
      patterns of neural response to each category of scene, the magnitude of the
      within-category similarity varied across different scenes. To determine whether
      this variation in the categorical response to scenes could reflect variation in
      the low-level image properties, we measured the similarity of images from each
      category of scene. Although we found that the low-level properties of images from
      each category were more similar to each other than to other categories of scenes,
      we also found that the magnitude of the within-category similarity varied across
      different scenes. Finally, we compared variation in the neural response to
      different categories of scenes with corresponding variation in the low-level
      image properties. We found a strong positive correlation between the similarity
      in the patterns of neural response to different scenes and the similarity in the
      image properties. Together, these results suggest that categorical patterns of
      response to scenes are linked to the low-level properties of the images. 

PMID- 24862073
TI  - Simultaneous recording of MEG, EEG and intracerebral EEG during visual
      stimulation: from feasibility to single-trial analysis.
AB  - Electroencephalography (EEG), magnetoencephalography (MEG), and intracerebral
      stereotaxic EEG (SEEG) are the three neurophysiological recording techniques,
      which are thought to capture the same type of brain activity. Still, the
      relationships between non-invasive (EEG, MEG) and invasive (SEEG) signals remain
      to be further investigated. In early attempts at comparing SEEG with either EEG
      or MEG, the recordings were performed separately for each modality. However such
      an approach presents substantial limitations in terms of signal analysis. The
      goal of this technical note is to investigate the feasibility of simultaneously
      recording these three signal modalities (EEG, MEG and SEEG), and to provide
      strategies for analyzing this new kind of data. Intracerebral electrodes were
      implanted in a patient with intractable epilepsy for presurgical evaluation
      purposes. This patient was presented with a visual stimulation paradigm while the
      three types of signals were simultaneously recorded. The analysis started with a
      characterization of the MEG artifact caused by the SEEG equipment. Next, the
      average evoked activities were computed at the sensor level, and cortical source
      activations were estimated for both the EEG and MEG recordings; these were shown
      to be compatible with the spatiotemporal dynamics of the SEEG signals. In the
      average time-frequency domain, concordant patterns between the MEG/EEG and SEEG
      recordings were found below the 40 Hz level. Finally, a fine-grained coupling
      between the amplitudes of the three recording modalities was detected in the time
      domain, at the level of single evoked responses. Importantly, these correlations
      have shown a high level of spatial and temporal specificity. These findings
      provide a case for the ability of trimodal recordings (EEG, MEG, and SEEG) to
      reach a greater level of specificity in the investigation of brain signals and
      functions.

PMID- 24862074
TI  - The salience network is responsible for switching between the default mode
      network and the central executive network: replication from DCM.
AB  - With the advent of new analysis methods in neuroimaging that involve independent
      component analysis (ICA) and dynamic causal modelling (DCM), investigations have
      focused on measuring both the activity and connectivity of specific brain
      networks. In this study we combined DCM with spatial ICA to investigate network
      switching in the brain. Using time courses determined by ICA in our dynamic
      causal models, we focused on the dynamics of switching between the default mode
      network (DMN), the network which is active when the brain is not engaging in a
      specific task, and the central executive network (CEN), which is active when the
      brain is engaging in a task requiring attention. Previous work using Granger
      causality methods has shown that regions of the brain which respond to the degree
      of subjective salience of a stimulus, the salience network, are responsible for
      switching between the DMN and the CEN (Sridharan et al., 2008). In this work we
      apply DCM to ICA time courses representing these networks in resting state data.
      In order to test the repeatability of our work we applied this to two independent
      datasets. This work confirms that the salience network drives the switching
      between default mode and central executive networks and that our novel technique
      is repeatable. 

PMID- 24862071
TI  - Optical imaging of disrupted functional connectivity following ischemic stroke in
      mice.
AB  - Recent human neuroimaging studies indicate that spontaneous fluctuations in
      neural activity, as measured by functional connectivity magnetic resonance
      imaging (fcMRI), are significantly affected following stroke. Disrupted
      functional connectivity is associated with behavioral deficits and has been
      linked to long-term recovery potential. FcMRI studies of stroke in rats have
      generally produced similar findings, although subacute cortical reorganization
      following focal ischemia appears to be more rapid than in humans. Similar studies
      in mice have not been published, most likely because fMRI in the small mouse
      brain is technically challenging. Extending functional connectivity methods to
      mouse models of stroke could provide a valuable tool for understanding the link
      between molecular mechanisms of stroke repair and human fcMRI findings at the
      system level. We applied functional connectivity optical intrinsic signal imaging
      (fcOIS) to mice before and 72 h after transient middle cerebral artery occlusion
      (tMCAO) to examine how graded ischemic injury affects the relationship between
      functional connectivity and infarct volume, stimulus-induced response, and
      behavior. Regional changes in functional connectivity within the MCA territory
      were largely proportional to infarct volume. However, subcortical damage affected
      functional connectivity in the somatosensory cortex as much as larger infarcts of
      cortex and subcortex. The extent of injury correlated with cortical activations
      following electrical stimulation of the affected forelimb and with functional
      connectivity in the somatosensory cortex. Regional homotopic functional
      connectivity in motor cortex correlated with behavioral deficits measured using
      an adhesive patch removal test. Spontaneous hemodynamic activity within the
      infarct exhibited altered temporal and spectral features in comparison to intact
      tissue; failing to account for these regional differences significantly affected
      apparent post-stroke functional connectivity measures. Thus, several results were
      strongly dependent on how the resting-state data were processed. Specifically,
      global signal regression alone resulted in apparently distorted functional
      connectivity measures in the intact hemisphere. These distortions were corrected
      by regressing out multiple sources of variance, as performed in human fcMRI. We
      conclude that fcOIS provides a sensitive imaging modality in the murine stroke
      model; however, it is necessary to properly account for altered hemodynamics in
      injured brain to obtain accurate measures of functional connectivity.

PMID- 24862075
TI  - On nodes and modes in resting state fMRI.
AB  - This paper examines intrinsic brain networks in light of recent developments in
      the characterisation of resting state fMRI timeseries--and simulations of
      neuronal fluctuations based upon the connectome. Its particular focus is on
      patterns or modes of distributed activity that underlie functional connectivity.
      We first demonstrate that the eigenmodes of functional connectivity--or
      covariance among regions or nodes--are the same as the eigenmodes of the
      underlying effective connectivity, provided we limit ourselves to symmetrical
      connections. This symmetry constraint is motivated by appealing to proximity
      graphs based upon multidimensional scaling. Crucially, the principal modes of
      functional connectivity correspond to the dynamically unstable modes of effective
      connectivity that decay slowly and show long term memory. Technically, these
      modes have small negative Lyapunov exponents that approach zero from below.
      Interestingly, the superposition of modes--whose exponents are sampled from a
      power law distribution--produces classical 1/f (scale free) spectra. We
      conjecture that the emergence of dynamical instability--that underlies intrinsic
      brain networks--is inevitable in any system that is separated from external
      states by a Markov blanket. This conjecture appeals to a free energy formulation
      of nonequilibrium steady-state dynamics. The common theme that emerges from these
      theoretical considerations is that endogenous fluctuations are dominated by a
      small number of dynamically unstable modes. We use this as the basis of a dynamic
      causal model (DCM) of resting state fluctuations--as measured in terms of their
      complex cross spectra. In this model, effective connectivity is parameterised in
      terms of eigenmodes and their Lyapunov exponents--that can also be interpreted as
      locations in a multidimensional scaling space. Model inversion provides not only
      estimates of edges or connectivity but also the topography and dimensionality of
      the underlying scaling space. Here, we focus on conceptual issues with simulated
      fMRI data and provide an illustrative application using an empirical multi-region
      timeseries.

PMID- 24862076
TI  - You'd better think twice: post-decision perceptual confidence.
AB  - Current findings suggest that confidence emerges only after decision making.
      However, the temporal and neural dynamics of the emergence of post-decision
      confidence--a metacognitive judgement--are not fully explored. To gain insight
      into the dynamics of post-decision confidence processing and to disentangle the
      processes underlying confidence judgements and decision making, we applied a
      tactile discrimination task during functional magnetic resonance imaging (fMRI).
      Our results revealed that reaction times to post-decision confidence depend on
      the level of confidence, suggesting that post-decision confidence in a perceptual
      choice is not processed in parallel to perceptual decision making. Moreover, we
      demonstrated by the parametric analysis of fMRI data that post-decisionally
      modelled confidence processing can be distinguished from processes related to
      decision making through anatomical location and through the pattern of neural
      activity. In contrast to perceptual decision making, post-decision confidence
      appears to be strictly allocated to a prefrontal network of brain regions,
      primarily the anterior and dorsolateral prefrontal cortex, areas that have been
      related to metacognition. Moreover, the processes underlying decision making and
      post-decision confidence may share recruitment of the dorsolateral prefrontal
      cortex, although the former probably has distinct functions with regard to
      processing of perceptual choices and post-decision confidence. Thus, this is the
      first fMRI study to disentangle the processes underlying post-decision confidence
      and decision making on behavioural, neuroanatomical, and neurofunctional levels.
      With regard to the temporal evolution of post-decision confidence, results of the
      present study provide strong support for the most recent theoretical models of
      human perceptual decision making, and thus provide implications for investigating
      confidence in perceptual paradigms.

PMID- 24862077
TI  - Sexually dimorphic functional connectivity in response to high vs. low energy
      dense food cues in obese humans: an fMRI study.
AB  - Sexually-dimorphic behavioral and biological aspects of human eating have been
      described. Using psychophysiological interaction (PPI) analysis, we investigated
      sex-based differences in functional connectivity with a key emotion-processing
      region (amygdala, AMG) and a key reward-processing area (ventral striatum, VS) in
      response to high vs. low energy-dense (ED) food images using blood oxygen level
      dependent (BOLD) functional magnetic resonance imaging (fMRI) in obese persons in
      fasted and fed states. When fed, in response to high vs. low-ED food cues, obese
      men (vs. women) had greater functional connectivity with AMG in right subgenual
      anterior cingulate, whereas obese women had greater functional connectivity with
      AMG in left angular gyrus and right primary motor areas. In addition, when fed,
      AMG functional connectivity with pre/post-central gyrus was more associated with
      BMI in women (vs. men). When fasted, obese men (vs. women) had greater functional
      connectivity with AMG in bilateral supplementary frontal and primary motor areas,
      left precuneus, and right cuneus, whereas obese women had greater functional
      connectivity with AMG in left inferior frontal gyrus, right thalamus, and
      dorsomedial prefrontal cortex. When fed, greater functional connectivity with VS
      was observed in men in bilateral supplementary and primary motor areas, left
      postcentral gyrus, and left precuneus. These sex-based differences in functional
      connectivity in response to visual food cues may help partly explain differential
      eating behavior, pathology prevalence, and outcomes in men and women. 

PMID- 24862080
TI  - The effect of linear mixing in the EEG on Hurst exponent estimation.
AB  - Although the long-range temporal correlation (LRTC) of the amplitude fluctuations
      of neuronal EEG/MEG oscillations is widely acknowledged, the majority of studies
      to date have been performed in sensor space, disregarding the mixing effects
      implied by volume conduction and confounding noise. While the effect of mixing on
      the evaluation of evoked responses and connectivity measures has been extensively
      studied, there are, to date, no studies reporting on the differences in the
      values of the estimated Hurst exponents when moving between sensor and source
      space representations of the multivariate data or on the effect of noise. Such
      differences, if not duly acknowledged, may lead to erroneous data
      interpretations. We show in simulations and in theory that measuring Hurst
      exponents in sensor space may lead to an incomplete picture of the LRTC
      properties of the underlying data and that noise may significantly bias the
      estimate of the Hurst exponent of the underlying signal. Moreover, these
      predictions are confirmed in real data, where we analyze the amplitude dynamics
      of neuronal oscillations in the resting state from EEG data. By moving either to
      an independent components representation or to a source representation which
      maximizes the signal to noise ratio in the alpha frequency range, we observe
      greater variance, skewness and kurtosis over measured Hurst exponents than in
      sensor space. We confirm the suitability of conventional source separation
      methodology by introducing a novel algorithm HeMax which obtains a source
      maximizing the Hurst exponent in the amplitude dynamics of narrow band
      oscillations. Our findings imply that the long-range correlative properties of
      the EEG should be studied in source space, in such a way that the SNR is
      maximized, or at least with spatial decomposition techniques approximating source
      activities, rather than in sensor space. 

PMID- 24862078
TI  - Dopamine release in nucleus accumbens during rewarded task switching measured by
      [11C]raclopride.
AB  - Reward and motivation have positive influences on cognitive-control processes in
      numerous settings. Models of reward implicate corticostriatal loops and the
      dopamine (DA) system, with special emphasis on D2 receptors in nucleus accumbens
      (NAcc). In this study, 11 right-handed males (35-40 years) were scanned with
      positron emission tomography (PET) in a single [(11)C]raclopride dynamic scan
      during rewarded and non-rewarded task switching. Rewarded task switching
      (relative to baseline task switching) decreased [(11)C]raclopride binding in
      NAcc. Decreasing NAcc [(11)C]raclopride binding was strongly associated with task
      reaction time measures that reflect individual differences in effort and control
      strategies. Voxelwise analyses additionally revealed reward-related DA release in
      anterodorsal caudate, a region previously associated with task-switching. These
      PET findings provide evidence for striatal DA release during motivated cognitive
      control, and further suggest that NAcc DA release predicts the task reaction time
      benefits of reward incentives. 

PMID- 24862079
TI  - Handedness and effective connectivity of the motor system.
AB  - Handedness denotes the individual predisposition to consistently use the left or
      right hand for most types of skilled movements. A putative neurobiological
      mechanism for handedness consists in hemisphere-specific differences in network
      dynamics that govern unimanual movements. We, therefore, used functional magnetic
      resonance imaging and dynamic causal modeling to investigate effective
      connectivity between key motor areas during fist closures of the dominant or non
      dominant hand performed by 18 right- and 18 left-handers. Handedness was assessed
      employing the Edinburgh-Handedness-Inventory (EHI). The network of interest
      consisted of key motor regions in both hemispheres including the primary motor
      cortex (M1), supplementary motor area (SMA), ventral premotor cortex (PMv), motor
      putamen (Put) and motor cerebellum (Cb). The connectivity analysis revealed that
      in right-handed subjects movements of the dominant hand were associated with
      significantly stronger coupling of contralateral (left, i.e., dominant) SMA with
      ipsilateral SMA, ipsilateral PMv, contralateral motor putamen and contralateral
      M1 compared to equivalent connections in left-handers. The degree of handedness
      as indexed by the individual EHI scores also correlated with coupling parameters
      of these connections. In contrast, we found no differences between right- and
      left-handers when testing for the effect of movement speed on effective
      connectivity. In conclusion, the data show that handedness is associated with
      differences in effective connectivity within the human motor network with a
      prominent role of SMA in right-handers. Left-handers featured less asymmetry in
      effective connectivity implying different hemispheric mechanisms underlying hand
      motor control compared to right-handers. 

PMID- 24862081
TI  - Gross, histologic, and micro-computed tomographic anatomy of the lacrimal system
      of snakes.
AB  - OBJECTIVE: To describe the lacrimal system of snakes using contrast micro
      computed tomography (micro-CT) with 3-dimensional reconstruction, fluorescein
      passage ('Jones') testing, histology, and gross dissection. ANIMALS STUDIED: One
      royal python and 19 snake cadavers representing 10 species. PROCEDURES: Direct
      observation following injection of fluorescein into the subspectacular space,
      micro-CT following injection of three contrast agents into the subspectacular
      space, gross dissection following injection of latex into the subspectacular
      space, and histopathology. RESULTS: Injection of fluorescein confirmed patency,
      but not course of the lacrimal duct. Barium enabled clear visualization of the
      lacrimal duct, whereas two iodinated contrast agents proved inadequate.
      Collectively, micro-CT, anatomic dissections, and histology suggest tears are
      produced by a single, large, serous, retrobulbar gland, released into the
      subspectacular space via several ductules, and drained through a single punctum
      originating in the ventronasal subspectacular space, and the lacrimal duct, which
      takes one of three routes of variable tortuosity before opening into the oral
      cavity in close association with the opening of the duct of the vomeronasal
      organ. CONCLUSIONS: The ophidian lacrimal duct has a generally tortuous course,
      and the details of its anatomy are species-variable. The tortuous course of the
      duct likely predisposes snakes to duct occlusion and must be considered when
      planning medical and surgical interventions in snakes with pseudobuphthalmos and
      subspectacular abscessation.

PMID- 24862082
TI  - Increasing cannabis use: what we still need to know about its effects on the
      lung.

PMID- 24862083
TI  - Cause of fetal demise in first-trimester parvovirus infection: anemia,
      placentitis or myocarditis?

PMID- 24862084
TI  - The biological activities and chemical composition of Pereskia species
      (Cactaceae)--a review.
AB  - The exploration of nature as a source of sustainable, novel bioactive substances
      continues to grow as natural products play a significant role in the search for
      new therapeutic and agricultural agents. In this context, plants of the genus
      Pereskia (Cactaceae) have been studied for their biological activities, and are
      evolving as an interesting subject in the search for new, bioactive compounds.
      These species are commonly used as human foodstuffs and in traditional medicine
      to treat a variety of diseases. This review focuses on the bioactivity and
      chemical composition of the genus Pereskia, and aims to stimulate further studies
      on the chemistry and biological potential of the genus. 

PMID- 24862085
TI  - A multidisciplinary intervention programme has positive effects on quality of
      life in overweight and obese preschool children.
AB  - AIM: Up to 18.1% of Dutch children aged 3-5 are overweight and up to 3.3% are
      obese, with higher levels in girls. This study assessed the effect of a
      multidisciplinary intervention programme on health-related quality of life
      (HRQoL) in this patient group. METHODS: We randomised 75 children to a
      multidisciplinary intervention, comprising dietary advice, exercise sessions and
      psychological counselling for parents or the standard care programme, providing
      healthy lifestyle advice. The parents completed quality of life and child health
      questionnaires at baseline and after 16 weeks and 12 months. RESULTS: At 16
      weeks, children in the intervention group experienced more bodily pain and less
      mental health than the standard care group, but at 12 months, this difference
      disappeared and they showed a more positive change in HRQoL than the standard
      care group, especially for the physical domain. When we combined both groups, a
      decreased BMIz-score over 12 months was associated with increased global health
      and reduced visceral fat correlated with increased general health. CONCLUSION: At
      12 months, a multidisciplinary intervention programme for overweight and obese
      children aged 3-5 years had beneficial effects on HRQoL, especially for the
      physical domain. Reduced obesity parameters correlated with several increased
      HRQoL parameters.

PMID- 24862086
TI  - Geraniol blocks calcium and potassium channels in the mammalian myocardium:
      useful effects to treat arrhythmias.
AB  - Geraniol is a monoterpene present in several essential oils, and it is known to
      have a plethora of pharmacological activities. In this study, we explored the
      contractile and electrophysiological properties of geraniol and its
      antiarrhythmic effects in the heart. The geraniol effects on atrial
      contractility, L-type Ca(2+) current, K(+) currents, action potential (AP)
      parameters, ECG profile and on the arrhythmia induced by ouabain were evaluated.
      In the atrium, geraniol reduced the contractile force (~98%, EC = 1,510 +/- 160
      MUM) and diminished the positive inotropism of CaCl2 and BAY K8644. In
      cardiomyocytes, the IC a,L was reduced by 50.7% (n = 5) after perfusion with 300
      MUM geraniol. Moreover, geraniol prolonged the AP duration (APD) measured at 50%
      (n = 5) after repolarization, without changing the resting potential. The
      increased APD could be attributed to the blockade of the transient outward K(+)
      current (Ito ) (59.7%, n = 4), the non-inactivation K(+) current (Iss ) (39.2%, n
      = 4) and the inward rectifier K(+) current (IK 1 ) (33.7%, n = 4). In isolated
      hearts, geraniol increased PRi and QTi without affecting the QRS complex (n = 6),
      and it reduced both the left ventricular pressure (83%) and heart rate (16.5%).
      Geraniol delayed the time to onset of ouabain-induced arrhythmias by 128%,
      preventing 30% of the increase in resting tension (n = 6). Geraniol exerts its
      negative inotropic and chronotropic responses in the heart by decreasing both L
      type Ca(2+) and voltage-gated K(+) currents, ultimately acting against ouabain
      induced arrhythmias. 

PMID- 24862088
TI  - SERS-fluorescence joint spectral encoded magnetic nanoprobes for multiplex cancer
      cell separation.
AB  - A new kind of cancer cell separation method is demonstrated, using surface
      enhanced Raman scattering (SERS) and fluorescence dual-encoded magnetic
      nanoprobes. The designed nanoprobes can realize SERS-fluorescence joint spectral
      encoding (SFJSE) and greatly improve the multiplexing ability. The nanoprobes
      have four main components, that is, the magnetic core, SERS generator,
      fluorescent agent, and targeting antibody. These components are assembled with a
      multi-layered structure to form the nanoprobes. Specifically, silica-coated
      magnetic nanobeads (MBs) are used as the inner core. Au core-Ag shell nanorods
      (Au@Ag NRs) are employed as the SERS generators and attached on the silica-coated
      MBs. After burying these Au@Ag NRs with another silica layer, CdTe quantum dots
      (QDs), that is, the fluorescent agent, are anchored onto the silica layer.
      Finally, antibodies are covalently linked to CdTe QDs. SFJSE is fulfilled by
      using different Raman molecules and QDs with different emission wavelengths. By
      utilizing four human cancer cell lines and one normal cell line as the model
      cells, the nanoprobes can specifically and simultaneously separate target cancer
      cells from the normal ones. This SFJSE-based method greatly facilitates the
      multiplex, rapid, and accurate cancer cell separation, and has a prosperous
      potential in high-throughput analysis and cancer diagnosis. 

PMID- 24862089
TI  - Direct metal-catalyzed regioselective functionalization of enamides.
AB  - Enamides are stable enamine surrogates and provide key intermediates for the
      synthesis of small but complex nitrogen-containing compounds. Metal-catalyzed
      regioselective functionalization of enamides provides a rapid method to
      synthesize useful nitrogen containing heterocycles. This review discloses the
      recent progress made in the development of the C-H functionalization of enamides
      involving efficient and atom-economical routes. Syntheses of different
      heterocycles are classified based on the site reactivity of enamides and key
      mechanistic insights are given for each transformation.

PMID- 24862090
TI  - The enabling effect of social support on vaccination uptake via self-efficacy and
      planning.
AB  - PURPOSE: In the context of worksite influenza vaccination programmes, social
      support, action planning and perceived self-efficacy were examined as predictors
      of participation. Mechanisms among these predictors were analysed by applying the
      enabling effect model to vaccination. Moreover, this model was extended by the
      inclusion of planning. METHODS: In a large German company, a survey on influenza
      vaccination was launched with 200 employees taking part in the five-month follow
      up. Using regression procedures, a sequential mediation model was examined,
      leading from social support via self-efficacy and planning to vaccination
      behaviour. RESULTS: The three predictors jointly accounted for 47% of the
      vaccination participation variance. The enabling effect model was confirmed,
      highlighting how social support may promote self-efficacy beliefs. Further
      analysis yielded the extended model, revealing planning as a mediator between
      self-efficacy and subsequent behaviour while the indirect path from social
      support via self-efficacy to behaviour remained. CONCLUSIONS: Multiple step
      mediation analysis underscored the relevance of social support and self-efficacy.
      It also revealed planning as a proximal factor that may facilitate participation
      in a worksite influenza vaccination programme.

PMID- 24862091
TI  - Lobular carcinoma in situ with collagenous spherulosis: clinicopathologic
      characteristics of 38 cases.

PMID- 24862087
TI  - Bone marrow-derived mesenchymal stem cells for the treatment of heart failure.
AB  - Heart failure remains a major cause of death and disability, requiring rapid
      development of new therapies. Bone marrow-derived mesenchymal stem cell (MSC)
      based therapy is an emerging approach for the treatment of both acute and chronic
      heart failure. Following successful experimental studies in a range of models,
      more than 40 clinical trials of MSC-based therapy for heart failure have now been
      registered, and the results of completed clinical trials so far have shown
      feasibility and safety of this approach with therapeutic potential suggested
      (though preliminarily). However, there appear to be several critical issues to be
      solved before this treatment could become a widespread standard therapy for heart
      failure. In this review, we comprehensively and systemically summarize a total of
      73 preclinical studies and 11 clinical trial reports published to date. By
      analyzing the data in these reports, (1) improvement in the cell delivery method
      to the heart in order to enhance donor cell engraftment, (2) elucidation of
      mechanisms underpinning the therapeutic effects of the treatment differentiation
      and/or treatment secretion, and (3) validation of the utility of allogeneic MSCs
      which could enhance the efficacy and expand the application/indication of this
      therapeutic approach are highlighted as future perspectives. These important
      respects are further discussed in this review article with referencing latest
      scientific and clinical information. 

PMID- 24862092
TI  - What makes people talk about antibiotics on social media? A retrospective
      analysis of Twitter use.
AB  - OBJECTIVES: Social media has reshaped individual and institutional communication.
      The unrestricted access to spontaneous views and opinions of society can enrich
      the evaluation of healthcare interventions. Antimicrobial resistance has been
      identified as a global threat to health requiring collaboration between
      clinicians and healthcare users. We sought to explore events and individuals
      influencing the discourse about antibiotics on Twitter. METHODS: A web-based tool
      (www.topsy.com) was used to detect daily occurrences of the word 'antibiotic'
      from 24 September 2012 to 23 September 2013 in worldwide Tweets. Activity peaks
      (message frequency over three times that of baseline) were analysed to identify
      events leading to the increase. RESULTS: Of 135 billion messages posted during
      the study period, 243000 (0.000002%) referred to 'antibiotic'. The greatest
      activity increases appeared after: (i) the UK Chief Medical Officer's (CMO's)
      declaration of antimicrobial resistance as a national risk (January 2013 and
      March 2013); (ii) the release of the US CDC's report on antimicrobial resistance
      (September 2013); and (iii) the US FDA announcement on azithromycin safety
      concerns (March 2013). The CMO report in March reached an estimated worldwide
      audience of 20 million users in a single day. However, the frequency of
      antibiotic Tweets returned to basal levels within 48 h of all four peaks in
      activity. CONCLUSIONS: Institutional events can rapidly amplify antibiotic
      discussions on social media, but their short lifespan may hinder their public
      impact. Multipronged strategies may be required to prolong responses. Developing
      methods to refine social media monitoring to evaluate the impact and
      sustainability of societal engagement in the antimicrobial resistance agenda
      remains essential.

PMID- 24862093
TI  - Pre-clinical development of a combination microbicide vaginal ring containing
      dapivirine and darunavir.
AB  - OBJECTIVES: Combination microbicide vaginal rings may be more effective than
      single microbicide rings at reducing/preventing sexual transmission of HIV. Here,
      we report the pre-clinical development and macaque pharmacokinetics of matrix
      type silicone elastomer vaginal rings containing dapivirine and darunavir.
      METHODS: Macaque rings containing 25 mg dapivirine, 100 mg dapivirine, 300 mg
      darunavir or 100 mg dapivirine+300 mg darunavir were manufactured and
      characterized by differential scanning calorimetry. In vitro release was assessed
      into isopropanol/water and simulated vaginal fluid. Macaque vaginal fluid and
      blood serum concentrations for both antiretrovirals were measured during 28 day
      ring use. Tissue levels were measured on day 28. Ex vivo challenge studies were
      performed on vaginal fluid samples and IC50 values were calculated. RESULTS:
      Darunavir caused a concentration-dependent reduction in the dapivirine melting
      temperature in both solid drug mixes and in the combination ring. In vitro
      release from rings was dependent on drug loading, the number of drugs present and
      the release medium. In macaques, serum concentrations of both microbicides were
      maintained between 10(1) and 10(2) pg/mL. Vaginal fluid levels ranged between
      10(3) and 10(4) ng/g and between 10(4) and 10(5) ng/g for dapivirine and
      darunavir, respectively. Both dapivirine and darunavir showed very similar
      concentrations in each tissue type; the range of drug tissue concentrations
      followed the general rank order: vagina (1.8 * 10(3)-3.8 * 10(3) ng/g)  > cervix
      (9.4 * 10(1)-3.9 * 10(2) ng/g)  > uterus (0-108 ng/g)  > rectum (0-40 ng/g).
      Measured IC50 values were >2 ng/mL for both compounds. CONCLUSIONS: Based on
      these results, and in light of recent clinical progress of the 25 mg dapivirine
      ring, a combination vaginal ring containing dapivirine and darunavir is a viable
      second-generation HIV microbicide candidate.

PMID- 24862095
TI  - Complete sequences of IncHI1 plasmids carrying blaCTX-M-1 and qnrS1 in equine
      Escherichia coli provide new insights into plasmid evolution.
AB  - OBJECTIVES: To determine the structure of two multidrug-resistant IncHI1 plasmids
      carrying blaCTX-M-1 in Escherichia coli isolates disseminated in an equine clinic
      in the Czech Republic. METHODS: A complete nucleotide sequencing of 239 kb IncHI1
      (pEQ1) and 287 kb IncHI1/X1 (pEQ2) plasmids was performed using the 454-Genome
      Sequencer FLX system. The sequences were compared using bioinformatic tools with
      other sequenced IncHI1 plasmids. RESULTS: A comparative analysis of pEQ1 and pEQ2
      identified high nucleotide identity with the IncHI1 type 2 plasmids. A novel 24
      kb module containing an operon involved in short-chain fructooligosaccharide
      uptake and metabolism was found in the pEQ backbones. The role of the pEQ
      plasmids in the metabolism of short-chain fructooligosaccharides was demonstrated
      by studying the growth of E. coli cells in the presence of these sugars. The
      module containing the blaCTX-M-1 gene was formed by a truncated macrolide
      resistance cluster and flanked by IS26 as previously observed in IncI1 and IncN
      plasmids. The IncHI1 plasmid changed size and gained the quinolone resistance
      gene qnrS1 as a result of IS26-mediated fusion with an IncX1 plasmid.
      CONCLUSIONS: Our data highlight the structure and evolution of IncHI1 from equine
      E. coli. A plasmid-mediated sugar metabolic element could play a key role in
      strain fitness, contributing to the successful dissemination and maintenance of
      these plasmids in the intestinal microflora of horses.

PMID- 24862096
TI  - Oral health and dental treatment needs of people with motor neurone disease.
AB  - BACKGROUND: People with motor neurone disease (MND) may present with physical
      limitations impacting on oral health and access to oral health care. This study
      aimed to assess the oral health status and treatment needs of people with MND in
      Victoria, Australia. METHODS: Patients with advanced MND attending a
      multidisciplinary MND clinic in Melbourne were recruited. Data collection
      included self-reporting questionnaires on previous dental experience, current
      oral hygiene practices and current dietary habits, a medical questionnaire, and a
      clinical examination charting participants' dentition, restorations, caries and
      periodontal status, plaque and gingival indices, and assessment of oral health.
      RESULTS: Thirty-three participants took part in the study with eight self
      reporting regular dental visits. No participant exhibited probing depths of more
      than 3 mm. Ten out of 27 dentate participants required extractions and
      restorations for retained roots and caries, while three presented with non
      carious cavities, lost restorations and fractured cusps. Oral health status was
      not affected by MND presentation in these participants. CONCLUSIONS: The study
      found that oral health was not affected by advanced MND. Participants' and
      clinical teams' motivation towards oral health care may have contributed to oral
      health. The dental profession should be involved as part of the multidisciplinary
      effort towards ongoing care.

PMID- 24862094
TI  - Tenofovir diphosphate concentrations and prophylactic effect in a macaque model
      of rectal simian HIV transmission.
AB  - OBJECTIVES: This study evaluated the relationship between intracellular tenofovir
      diphosphate concentrations in peripheral blood mononuclear cells and prophylactic
      efficacy in a macaque model for HIV pre-exposure prophylaxis (PrEP). METHODS:
      Macaques were challenged with simian HIV (SHIV) via rectal inoculation once
      weekly for up to 14 weeks. A control group (n=34) received no drug, a second
      group (n=6) received oral tenofovir disoproxil fumarate/emtricitabine 3 days
      before each virus challenge and a third group (n=6) received the same dosing plus
      another dose 2 h after virus challenge. PBMCs were collected just before each
      weekly virus challenge. The relationship between tenofovir diphosphate in PBMCs
      and prophylactic efficacy was assessed with a Cox proportional hazards model.
      RESULTS: The percentages of animals infected in the control, one-dose and two
      dose groups were 97, 83 and 17, respectively. The mean (SD) steady-state
      tenofovir diphosphate concentration (fmol/10(6) cells) was 15.8 (7.6) in the one
      dose group and 30.7 (10.1) in the two-dose group. Each 5 fmol tenofovir
      diphosphate/10(6) cells was associated with a 40% (95% CI 17%-56%) reduction in
      risk of SHIV acquisition, P=0.002. The tenofovir diphosphate concentration
      associated with a 90% reduction in risk (EC90) was 22.6 fmol/10(6) cells (95% CI
      13.8-60.8). CONCLUSIONS: The prophylactic EC90 for tenofovir diphosphate
      identified in macaques exposed rectally compares well with the EC90 previously
      identified in men who have sex with men (MSM; 16 fmol/10(6) cells, 95% CI 3-28).
      These results highlight the relevance of this model to inform human PrEP studies
      of oral tenofovir disoproxil fumarate/emtricitabine for MSM.

PMID- 24862097
TI  - Evaluation diagnostic usefulness of immunoglobulin light chains (Igkappa,
      Iglambda) and incomplete IGH D-J clonal gene rearrangements in patients with B
      cell non-Hodgkin lymphomas using BIOMED-2 protocol.
AB  - PURPOSE: Evaluation diagnostic usefulness of immunoglobulin light chains
      (Igkappa, Iglambda) and incomplete IGH D-J clonal gene rearrangements in formalin
      fixed, paraffin-embedded (FFPE) tissue of patients with B-cell non-Hodgkin
      lymphomas (B-NHL). MATERIALS AND METHODS: This study was performed on samples
      from 70 patients with B-NHL, including two cases of follicular lymphoma (FL), 20
      cases of diffuse large B-cell lymphoma (DLBCL), one case of mantle cell lymphoma
      (MCL), and 47 cases of B-cell neoplasm (non-classified), which had been
      previously assessed for complete IGH clonality, and failure to clarify gene
      rearrangements. We used a gold standard multiplex PCR protocol provided by
      European Biomedicine and Health (BIOMED-2) Concerted Action Project BMH4-CT98
      3936 for improvement of diagnosis and analysis of clonality gene rearrangement in
      lymphoma malignancies. RESULTS: Our results revealed a total positive
      monoclonality of 89 % (62/70) in Igkappa, Iglambda, and 11.4 % (8/70)
      polyclonality in gene rearrangements assay. The samples with positive clonality
      consisting (Igkappa: 45 %, Iglambda: 55 %) in DLBCL, (Igkappa: 100 %) in FL,
      (Iglambda: 100 %) in MCL, and (Igkappa: 47 %, Iglambda: 36 %) in B-cell neoplasm
      non-classified. None of the incomplete IGH D-J immunoglobulin gene families (0 %)
      showed monoclonality, and all samples demonstrated polyclonality pattern.
      CONCLUSIONS: Our findings on FFPE tissue revealed that immunoglobulin light
      chains clonality gene rearrangements assays using BIOMED-2 protocol, could be
      considered a valuable and reliable method for clonality detection, particularly
      in cases of failure of complete IGH gene rearrangements analysis. Clonal Ig gene
      rearrangements assay is applicable for routine diagnostic testing of
      lymphoproliferative disorders and as a reliable method for differentiating
      between malignant and benign lymphoma disorders.

PMID- 24862098
TI  - The effect of the rpoSam allele on gene expression and stress resistance in
      Escherichia coli.
AB  - The RNA polymerase associated with RpoS transcribes many genes related to
      stationary phase and stress survival in Escherichia coli. The DNA sequence of
      rpoS exhibits a high degree of polymorphism. A C to T transition at position 99
      of the rpoS ORF, which results in a premature amber stop codon often found in E.
      coli strains. The rpoSam mutant expresses a truncated and partially functional
      RpoS protein. Here, we present new evidence regarding rpoS polymorphism in common
      laboratory E. coli strains. One out of the six tested strains carries the rpoSam
      allele, but expressed a full-length RpoS protein owing to the presence of an
      amber supressor mutation. The rpoSam allele was transferred to a non-suppressor
      background and tested for RpoS level, stress resistance and for the expression of
      RpoS and sigma70-dependent genes. Overall, the rpoSam strain displayed an
      intermediate phenotype regarding stress resistance and the expression of sigma(S)
      dependent genes when compared to the wild-type rpoS(+) strain and to the rpoS
      null mutant. Surprisingly, overexpression of rpoSam had a differential effect on
      the expression of the sigma(70)-dependent genes phoA and lacZ that, respectively,
      encode the enzymes alkaline phosphatase and beta-galactosidase. The former was
      enhanced while the latter was inhibited by high levels of RpoSam.

PMID- 24862099
TI  - Chaperonin containing TCP1, subunit 8 (CCT8) is upregulated in hepatocellular
      carcinoma and promotes HCC proliferation.
AB  - The development of molecular pathogenesis of hepatocellular carcinoma (HCC) is
      complex and involves alterations in the expression and conformation of assorted
      oncoproteins and tumor suppressors. Chaperonin containing TCP1 (CCT) is a cytolic
      molecular chaperone complex that is required for the correct folding of numerous
      proteins. In this study, we investigated a possible involvement of CCT subunit 8
      (CCT8) in HCC development. Immunohistochemical analysis was performed in 102
      human HCC samples. High CCT8 expression was detected in clinical HCC samples
      compared with adjacent noncancerous tissues. The univariate and multivariate
      survival analyses were also performed to determine their prognostic significance.
      Western blot confirmed the high expression of CCT8 in HCC compared with adjacent
      normal tissue. Moreover, the biological significance of the aberrant expression
      of CCT8 was investigated in HCC cell lines. Expression of CCT8 was correlated
      directly with the histologic grades and tumor size of HCC and high expression of
      CCT8 was associated with a poor prognosis. CCT8 depletion by siRNA inhibited cell
      proliferation and blocked S-phase entry in HuH7 cells. These results suggested
      that CCT8 might be an oncogene and participate in HCC cell proliferation. These
      findings provide a potential therapeutic strategy for the treatment of HCC. 

PMID- 24862101
TI  - Abstracts of the 12th European Society for Pediatric Dermatology (ESPD) Congress,
      12-14 June, 2014, Kiel, Germany.

PMID- 24862100
TI  - Polypharmacy and medication regimen complexity as factors associated with
      hospital discharge destination among older people: a prospective cohort study.
AB  - BACKGROUND: Older people often take multiple medications. It is a policy priority
      to facilitate older people to stay at home longer. Three-quarters of nursing home
      placements in the US are preceded by a hospitalization. OBJECTIVE: To investigate
      the association between polypharmacy and medication regimen complexity with
      hospital discharge destination among older people. METHODS: This prospective
      cohort study comprised patients aged >=70 years consecutively admitted to the
      Geriatric Evaluation and Management unit at a tertiary hospital in Adelaide,
      Australia, between October 2010 and December 2011. Medication regimen complexity
      at discharge was calculated using the 65-item validated Medication Regimen
      Complexity Index (MRCI). Unadjusted and adjusted relative risks (RRs) with 95 %
      confidence intervals (CIs) were calculated for medication-related factors
      associated with discharge directly to home versus non-community settings
      (rehabilitation, transition care, and residential aged care). RESULTS: From 163
      eligible patients, 87 were discharged directly to home (mean age 84.6 years,
      standard deviation [SD] 6.9; mean MRCI 26.1, SD 9.7), while 76 were discharged to
      non-community settings (mean age 85.8 years, SD 5.8; mean MRCI 29.9, SD 13.2).
      After adjusting for age, sex, comorbidity, and activities of daily living, having
      a high medication regimen complexity (MRCI >35) was inversely associated with
      discharge directly to home (RR 0.39; 95 % CI 0.20-0.73), whereas polypharmacy
      (>=9 medications) was not significantly associated with discharge directly to
      home (RR 0.97; 95 % CI 0.53-1.58). CONCLUSION: Having high medication regimen
      complexity was inversely associated with discharge directly to home, while
      polypharmacy was not associated with discharge destination.

PMID- 24862102
TI  - Comparative analyses of volatile organic compounds (VOCs) from patients, tumors
      and transformed cell lines for the validation of lung cancer-derived breath
      markers.
AB  - Breath analysis for the purpose of non-invasive diagnosis of lung cancer has
      yielded numerous candidate compounds with still questionable clinical relevance.
      To arrive at suitable volatile organic compounds our approach combined the
      analysis of different sources: isolated tumor samples compared to healthy lung
      tissues, and exhaled breath from lung cancer patients and healthy controls.
      Candidate compounds were further compared to substances previously identified in
      the comparison of transformed and normal lung epithelial cell lines. For human
      studies, a breath sampling device was developed enabling automated and CO2
      controlled collection of the end-tidal air. All samples were first
      preconcentrated on multibed sorption tubes and analyzed with gas chromatography
      mass spectrometry (GC-MS). Significantly (p < 0.05) higher concentrations in all
      three types of cancer samples studied were observed for ethanol and n-octane.
      Additional metabolites (inter alia 2-methylpentane, n-hexane) significantly
      released by lung cancer cells were observed at higher levels in cancer lung
      tissues and breath samples (compared to respective healthy controls) with
      statistical significance (p < 0.05) only in breath samples. The results obtained
      confirmed the cancer-related origin of volatile metabolites, e.g. ethanol and
      octane that were both detected at significantly (p < 0.05) elevated
      concentrations in all three kinds of cancer samples studied. This work is an
      important step towards identification of volatile breath markers of lung cancer
      through the demonstration of cancer-related origin of certain volatile
      metabolites. 

PMID- 24862103
TI  - Cerebral aneurysm coiling: a predictive model of hospitalization cost.
AB  - BACKGROUND: Several initiatives have been put in place to minimize healthcare
      expenditures. In new and evolving fields such as endovascular aneurysm treatment,
      there are limited data to support such measures. The objective of the present
      study was to develop and validate a predictive model of hospitalization cost
      after cerebral aneurysm coiling (CACo). METHODS: We performed a retrospective
      study involving CACo patients who were registered in the Nationwide Inpatient
      Sample database from 2005 to 2010. The cohort underwent 1:1 randomization to
      create derivation and validation subsamples. Regression techniques were used for
      the creation of a parsimonious predictive model. RESULTS: Of the 10,928 patients
      undergoing CACo, 6617 (60.5%) presented with unruptured and 4311 (39.5%) with
      ruptured aneurysms. Median hospitalization cost was US$35,446 (IQR $13,801
      $57,091). Common drivers of cost identified in the multivariate analysis
      included: length of stay; number of admission diagnoses and procedures; hospital
      size and region; patient income; hydrocephalus; acute renal failure; and
      seizures. The model was validated in independent cohorts and demonstrated a final
      R(2) value very similar to the initial model. The predicted and observed values
      in the validation cohort demonstrated good correlation. CONCLUSIONS: This
      national study identified significant drivers of hospitalization cost after CACo.
      The presented model can be utilized as an adjunct in the cost containment debate
      and the creation of data driven policies.

PMID- 24862104
TI  - Transarterial embolization of intractable nasal and oropharyngeal hemorrhage
      using liquid embolic agents.
AB  - INTRODUCTION: Intractable hemorrhage of the nasal or oropharyngeal cavities can
      be life threatening, and endovascular embolization is one of the few effective
      treatments for severe recurrent bleeds. Traditionally, embolic particles have
      been used for transarterial embolization. OBJECTIVE: To investigate the safety
      and efficacy of a less commonly performed treatment-namely, feeding artery
      occlusion with liquid embolic agents. METHODS: We retrospectively reviewed our
      neurointerventional database for patients who had undergone transarterial
      embolization for intractable nasal and oropharyngeal hemorrhage with Onyx, N
      butyl-2 cyanoacrylate (n-BCA) glue, or both, at our institution over a 5-year
      period from 2008 to 2013. RESULTS: Forty-six patients who underwent a total of 51
      procedures met the inclusion criteria. Causes of hemorrhage included neoplasm
      n=35 (68.6%), trauma n=12 (23.5%), and idiopathic n=4 (7.9%). The bleeding was
      oropharyngeal in 66.7%, nasal in 29.4%, and 3.9% originated from both sites.
      Embolic agents used were n-BCA in 26 cases (51.0%), Onyx in 22 cases (43.1%), and
      both agents in three cases (5.9%). Mean total procedural time was 93.1 min (range
      34-323 min), and mean fluoroscopy time was 39.1 min (10- 121 min). Mean follow-up
      time was 7.4 months (0.25-36 months). Five of the 46 patients (10.9%) required re
      embolization and one (2.0%) rebled during the same hospital stay. One
      periprocedural cardiovascular adverse event occurred that was unrelated to the
      embolic agent used, but no other complications were seen. CONCLUSIONS:
      Transarterial embolization with n-BCA or Onyx is a safe and effective treatment
      for patients with intractable nasal and oropharyngeal hemorrhage. Further
      prospective studies are warranted to confirm these findings.

PMID- 24862105
TI  - Balloon-augmented Onyx endovascular ligation: initial human experience and
      comparison with coil ligation.
AB  - INTRODUCTION: Carotid artery sacrifice remains an important procedure for
      cerebral vascular disorders despite the development of new endovascular devices.
      Conventional carotid artery sacrifice with detachable coils alone often requires
      numerous coils to complete occlusion. OBJECTIVE: To describe the initial human
      experience with balloon-augmented Onyx and coil vessel sacrifice based on our
      previous experience with animals. METHODS: We performed a retrospective review of
      patients who underwent carotid artery sacrifice between 2008 and 2012 in
      accordance with local investigational review board approval. Two methods were
      used to occlude carotid arteries-namely, combined Onyx and coil embolization and
      traditional coil embolization. We compared the two methods for the cost of
      embolizate, time to occlude the vessels, and the number of coils. RESULTS: Eight
      consecutive patients (combined group n=3, traditional group n=5) were assessed.
      The median cost of embolic material was $6321 in the combined Onyx and coil
      embolization group and $29 996 in the traditional coil embolization group. The
      median time from first coil placement to achievement of vessel occlusion was 52
      min in the Onyx group and 113 min in the coil embolization group. The median
      number of coils used was 4 in the Onyx group and 35 in the coil embolization
      group (p<0.05). No symptomatic complications or recurrences were seen in the
      combined group. CONCLUSIONS: Balloon-augmented Onyx endovascular ligation may
      reduce costs and fluoroscopy times during vessel sacrifice. Further studies in a
      larger number of patients are needed to confirm these findings.

PMID- 24862106
TI  - Functional bowel disorders in pregnancy: effect on quality of life, evaluation
      and management.
AB  - OBJECTIVE: To characterize functional bowel disorders in a population of pregnant
      women, evaluating effects on quality of life, management and follow up. DESIGN:
      Prospective cohort. SETTING: University center, USA. POPULATION: Women in the
      first trimester (n = 104). METHODS: After enrollment evaluations, measures were
      repeated in the third trimester. Overall bowel function was assessed using the
      Rome III Questionnaire for Functional Bowel Disorders. Quality of life symptoms
      were assessed with the Irritable Bowel Syndrome Quality of Life Measure.
      Physician documentation of bowel symptoms and subsequent treatment in pregnancy
      were ascertained by retrospective chart review. MAIN OUTCOME MEASURE: Quality of
      life in first trimester. RESULTS: A majority (75%) of the women at the first
      trimester evaluation reported having one or more functional bowel disorders. The
      overall quality of life status was rated highly functional, with a total average
      score of 94.9. Of the 75 women reporting functional bowel disorders, only 18
      (24%) were identified in the medical record. Overall documentation of any bowel
      function was identified in the majority (64%) of cases. Most commonly, no
      discussion of treatment was documented, and follow up was recorded in only 27% of
      women with dysfunction. CONCLUSIONS: Nearly three-quarters of women in the first
      trimester report symptoms consistent with functional bowel disorders. Overall
      quality of life measures are highly rated. There is a discrepancy between what
      women report regarding bowel dysfunction and what is documented by providers
      within the medical record.

PMID- 24862107
TI  - Racial disparities in an aging population: the relationship between age and race
      in the management of African American men with high-risk prostate cancer.
AB  - PURPOSE: To evaluate the relationship between age and race on the receipt of
      definitive therapy among men with high-risk prostate cancer (CaP). METHODS: We
      used the Surveillance, Epidemiology and End Results Program to identify 62,644
      men with high-risk CaP (PSA >20 or Gleason 8-10 or stage >=cT3a) diagnosed from
      2004 to 2010. Multivariable logistic regression analysis modeled the interaction
      between age and race and its association with receipt of definitive therapy on
      57,674 patients (47,879 white men; 9,795 African American [AA] men) with complete
      data on the covariates of interest. RESULTS: Among men age >=70, AA men had a
      higher risk of CaP-specific mortality (PCSM) compared to white men after
      adjusting for sociodemographic and prostate cancer-specific factors (Adjusted HR
      1.20; 95% CI 1.02-1.38; P=0.02). Nevertheless, a significant interaction between
      race and age was found (Pinteraction=0.01), such that the adjusted odds of
      receiving definitive treatment for AA vs. white was 0.67 (95% CI 0.62-0.73;
      P<0.001) among men age <70, but was 0.60 (95% CI 0.55-0.66; P<0.001) among men
      age >=70, suggesting increased racial disparity in the receipt of definitive
      treatment among older men. CONCLUSION: AA men with high-risk CaP are less likely
      to receive definitive therapy than white men. This disparity is significantly
      larger among men age >=70, despite excess PCSM among AA men in this group. With a
      rapidly expanding population of older minority men, this disparity should be
      urgently addressed to prevent increasing disparities in cancer care.

PMID- 24862108
TI  - Impact of comorbidities on pharmacotherapy of painful diabetic neuropathy in
      clinical practice.
AB  - AIMS: We evaluated the impact of baseline comorbidities on the effectiveness of
      duloxetine and anticonvulsants (pregabalin/gabapentin) in patients with painful
      diabetic neuropathy in clinical care. METHODS: Outcomes from a 6-month,
      observational study with 2575 patients initiating/switching DPNP treatment were
      analyzed post-hoc. Propensity scoring was used to adjust for baseline factors
      influencing treatment choice in 1523 patients receiving duloxetine or
      anticonvulsants. Analysis of covariance models with fixed effects for baseline
      pain, treatment, propensity score, baseline characteristics or comorbidities, and
      their interaction with treatment were used to estimate LSmean effects on Brief
      Pain Inventory (BPI) average pain and interference scores. RESULTS: 89.5% of
      patients reported comorbidities, including hypertension (70.5%), hyperlipidemia
      (39.2%), and depression (24.8%). Macrovascular complications (37.0%) and 'other
      chronic pain' (41.5%), particularly joint pain had an impact on both pain
      treatments, i.e. less improvement of average pain and interference of pain.
      Better treatment responses with duloxetine vs. anticonvulsants were observed in
      patients with depression, those with high baseline BPI total interference score,
      especially general activity, and in patients with joint pain. CONCLUSIONS:
      Comorbidities such as macroangiopathy and depression as well as pain
      characteristics should be considered in the treatment of DPNP as they may predict
      the effectiveness of duloxetine and anticonvulsants.

PMID- 24862109
TI  - The impact of exercise on the cognitive functioning of healthy older adults: a
      systematic review and meta-analysis.
AB  - Data from epidemiological, cross-sectional, and neuroimaging research show a
      relationship between higher levels of exercise and reduced risk of cognitive
      decline but evidence from randomised controlled trials (RCTs) is less consistent.
      This review examines the impact of aerobic exercise, resistance training, and Tai
      Chi on the cognitive function of older adults without known cognitive impairment.
      We investigate explanations for inconsistent results across trials and
      discrepancies between evidence from RCTs and other research data. Twenty-five
      RCTs were included in the review. Meta-analysis results revealed significant
      improvements for resistance training compared to stretching/toning on measures of
      reasoning (p<0.005); and for Tai Chi compared to 'no exercise' controls on
      measures of attention (p<0.001) and processing speed (p<0.00001). There were no
      significant differences between exercise and controls on any of the remaining 26
      comparisons. Results should be interpreted with caution however as differences in
      participant profiles, study design, exercise programmes, adherence rates, and
      outcome measures contribute to both discrepancies within the exercise research
      literature and inconsistent results across trials. 

PMID- 24862110
TI  - Ion-selective organic electrochemical transistors.
AB  - Ion-selective organic electrochemical transistors with sensitivity to potassium
      approaching 50 MUA dec(-1) are demonstrated. The remarkable sensitivity arises
      from the use of high transconductance devices, where the conducting polymer is in
      direct contact with a reference gel electrolyte and integrated with an ion
      selective membrane. 

PMID- 24862111
TI  - Ulnar impaction syndrome: incidence of lunotriquetral ligament degeneration and
      outcome of ulnar-shortening osteotomy.
AB  - PURPOSE: We hypothesized that most patients with ulnar impaction syndrome have
      degenerative changes of the proximal lunotriquetral (LT) membrane and that ulnar
      shortening osteotomy is an effective procedure in these patients. METHODS: We
      retrospectively reviewed 50 wrists of 49 patients with idiopathic ulnar impaction
      syndrome who underwent an arthroscopic evaluation at the time of ulnar-shortening
      osteotomy, and subsequently at plate removal. Based on the Geissler
      classification, patients were divided into group A, normal, and group B, grades I
      to IV. The degree of degeneration of the proximal LT membrane at first-look
      arthroscopy was compared with that at second-look arthroscopy. RESULTS: After
      ulnar-shortening osteotomy, both groups improved significantly in wrist range of
      motion and grip strength. According to the Mayo wrist score, 29, 18, and 3
      patients showed excellent, good, and fair results, respectively. Of the 50
      wrists, 25 had degenerative changes (group B) in the proximal LT membrane at the
      time of first-look arthroscopy. Of the 25 wrists in group B, 11 wrists improved
      based on the Geissler grade, 9 wrists showed no changes, and 2 wrists became
      worse. Clinically, patients demonstrated improvement after ulnar-shortening
      osteotomy regardless of the degree of degenerative LT ligament changes.
      CONCLUSIONS: Degenerative LT membrane changes that were seen in about half of our
      patients were mostly of a mild nature, and the clinical outcomes of ulnar
      shortening osteotomy were acceptable. TYPE OF STUDY/LEVEL OF EVIDENCE:
      Therapeutic IV.

PMID- 24862112
TI  - Supracondylar process syndrome: case report and literature review.
AB  - The supracondylar process is a congenital bone projection on the distal
      anteromedial humerus often associated with a ligament of Struthers, a fibrous
      connection between the process and medial epicondyle. It is largely asymptomatic
      and only on rare occasions presents with neurovascular compression resulting in a
      supracondylar process syndrome. This case report describes a 28-year-old woman
      with supracondylar process syndrome, and our management. The topic is further
      explored with a literature review of 43 reported cases. Analysis of the case
      reports indicates that isolated median nerve injuries are the most common. Other
      presentations such as fractures, vascular compromise, and ulnar nerve involvement
      are less frequent. 

PMID- 24862113
TI  - Has the teaching paradigm shifted? The future of education in the digital world.

PMID- 24862114
TI  - Relative motion splint: active motion after extensor tendon injury and repair.
AB  - The relative motion splint was initially developed to facilitate postoperative
      rehabilitation after repair of extensor tendon injuries at the dorsum of the hand
      and forearm. It has subsequently been used for rehabilitation of sagittal band
      injuries and after repair of closed attrition extensor tendon ruptures in
      rheumatoid arthritis. This is much less awkward than other braces and can readily
      be worn during normal past-time and work activities. This so-called immediate
      controlled active motion splinting protocol has also more recently been applied
      to both operative and nonsurgical rehabilitation for boutonniere deformity. 

PMID- 24862115
TI  - Technical tips for collagenase injection treatment for Dupuytren contracture.
AB  - We describe technical tips for injecting collagenase into Dupuytren cords based
      on experience acquired during the prerelease Food and Drug Administration
      clinical trials and with subsequent clinical practice. These tips include
      techniques for extracting the reconstituted enzyme efficiently from the vial,
      injecting the cord(s) with increased safety to the tendons, and anesthetizing the
      hand before manipulation. The tips are intended to supplement but by no means
      replace the manufacturer's prescribing information and training video. 

PMID- 24862116
TI  - Neuritis of the cutaneous nerves of the hand.

PMID- 24862117
TI  - The management of digital nerve injuries.
AB  - A tension-free coaptation is a key factor for the successful outcome of any nerve
      repair. A variety of host factors influence the outcome of digital nerve repair
      more than the type of repair per se. Although autologous graft remains the
      reference standard for reconstruction of any critical digital nerve defect,
      allografts and conduits have assumed an increasing role.

PMID- 24862118
TI  - Median nerve injury and repair.
AB  - Median nerve injuries in the forearm are reasonably common and can lead to
      devastating functional sequelae for the hand if they are not managed in a timely
      and appropriate fashion. Most nerve lacerations should be repaired soon after
      injury, and current widespread application of microsurgical techniques should
      lead to reasonable results in most individuals. Despite these advances, many
      patients do not have ideal outcomes from injuries to the median nerve and are
      often left with permanent sequelae. This article will discuss current techniques
      in the management of median nerve injuries, with the goal of preventing or
      alleviating the potential negative sequelae of these injuries. 

PMID- 24862119
TI  - A method to retrieve a broken guidewire.

PMID- 24862120
TI  - Cannulated screw shortening technique.

PMID- 24862121
TI  - Disability versus impairment.

PMID- 24862122
TI  - In reply.

PMID- 24862123
TI  - de Quervain tendinopathy: "success" and other subtleties.

PMID- 24862125
TI  - 7th international conference on thrombosis and hemostasis issues in cancer.
      Preface.

PMID- 24862124
TI  - In reply.

PMID- 24862126
TI  - Oncogenes and the coagulation system--forces that modulate dormant and aggressive
      states in cancer.
AB  - Cancers arise and progress genetically amidst profound perturbations of the
      microenvironmental and systemic homeostasis. This includes the coagulation
      system, which is a part of the vascular milieu (niche) that remains under the
      control of molecular events occurring within the cancer cell genome. Thus,
      activation of several prototypic oncogenic pathways, such as RAS, EGFR, HER2,
      MET, SHH and loss of tumor suppressors (PTEN, TP53) alter the expression,
      activity and vesicular release of coagulation effectors, as exemplified by tissue
      factor (TF). The cancer-specific determinants of coagulopathy are also
      illustrated by the emerging link between the expression profiles of coagulation
      related genes (coagulome) in glioblastoma multiforme (GBM), medulloblastoma (MB)
      and possibly other cancers and molecular subtypes of these respective tumors. The
      state of the coagulome is consequential for growth, metastasis and angiogenesis
      of established tumors, but could potentially also affect dormant cancer cells.
      For example, TF expression may trigger awakening of dormant glioma cells in mice
      in a manner involving recruitment of vascular and inflammatory cells, and
      resulting in lasting changes in the cancer cell genome and epigenome. Thus,
      coagulation system effectors could act as both targets and (indirect) inducers of
      genetic tumor progression, and a better understanding of this link may hold new
      diagnostic and therapeutic opportunities.

PMID- 24862127
TI  - Advances in the diagnosis and management of acute pulmonary embolism.
AB  - The diagnostic management of acute pulmonary embolism (PE) is complicated by its
      heterogeneous clinical presentation. Current diagnostic algorithms, combining
      clinical probability estimation with D-dimer testing and imaging tests, are very
      safe to exclude PE, although at costs of high numbers of CT-examinations. In view
      of cost- and time-saving as well as safety issues, several attempts have recently
      been undertaken to reduce the number of required imaging tests. Especially the
      age-adjusted D-dimer threshold has greatly improved the potential for non
      invasive exclusion of PE. Once the diagnosis of PE is established, immediate
      initiation of anticoagulant therapy is of vital importance. A new generation of
      direct oral anticoagulants, which overcomes the main disadvantages of
      conventional vitamin-K antagonists, has recently emerged. Risk stratification of
      hemodynamically stable PE patients with use of clinical decision rules, cardiac
      biomarkers or imaging tests, aids physicians in determining the most appropriate
      treatment approach for the individual patient. This is essential to differentiate
      patients at low risk of adverse outcome, who may be safely treated at home, from
      intermediate-risk patients, who require closer monitoring and for whom recent
      studies have evaluated the efficacy and safety of systemic thrombolytic therapy.
      This article reviews recent advances and challenges that remain in the diagnostic
      work-up and initial management of acute, clinically stable PE.

PMID- 24862128
TI  - Microenvironment and multiple myeloma spread.
AB  - In patients with multiple myeloma (MM), the bone marrow (BM) contains
      hematopoietic stem cells (HSCs) and non-hematopoietic cells. HSCs are able to
      give rise to all types of mature blood cells, while the non hematopoietic
      component includes mesenchymal stem cells (MSCs), fibroblasts, osteoblasts,
      osteoclasts, chondroclasts, endothelial cells, endothelial progenitor cells
      (EPCs), B and T lymphocytes, NK cells, erythrocytes, megakaryocytes, platelets,
      macrophages and mast cells. All of these cells form specialized "niches" in the
      BM microenvironment which are close to the vasculature ("vascular niche") or to
      the endosteum ("osteoblast niche"). The "vascular niche" is rich in blood vessels
      where endothelial cells and mural cells (pericytes and smooth muscle cells)
      create a microenvironment that affects the behavior of several stem and
      progenitor cells. The vessel wall serves as an independent niche for the
      recruitment of endothelial progenitor cells, MSCs and HSCs. The activation by
      angiogenic factors and inflammatory cytokines switch the "vascular niche" to
      promote MM tumor growth and spread. This review will focus on the mechanisms
      involved in the generation of signals released by endothelial cells in the
      "vascular niche" that promote tumor growth and spread in MM.

PMID- 24862129
TI  - Abnormal adhesion of red blood cells in polycythemia vera: a prothrombotic
      effect?
AB  - Polycythemia vera (PV) is a myeloproliferative neoplasm (MPN) characterised by
      the V617F activating mutation in the tyrosine kinase JAK2. PV patients exhibit
      increased haemoglobin levels and red cell mass because of uncontrolled
      proliferation of the erythroid lineage. Thrombosis and transformation to acute
      leukaemia are the major causes of morbidity and mortality in this disease.
      Increased thrombotic risk in PV patients is multifactorial and complex; it is
      associated with high levels of haemoglobin, impaired rheology and increased
      viscosity resulting from erythrocytosis. An additional parameter that might
      contribute to this risk was recently brought to light by work from our group
      showing abnormal activation of adhesion proteins in PV RBCs. In this review we
      provide an overview of these recent findings and discuss how the pro-adhesive
      features of JAK2V617F-positive red blood cells might initiate and contribute to
      the circulatory complications described in PV.

PMID- 24862130
TI  - Thrombo-hemorrhagic deaths in acute promyelocytic leukemia.
AB  - Acute promyelocytic leukemia (APL) has become the most curable form of acute
      myeloid leukemia after the advent of all-trans retinoic acid (ATRA). However,
      early deaths (ED) mostly due to the disease-associated coagulopathy remain the
      major cause of treatment failure. In particular, hemorrhagic events account for
      40-65% of ED and several prognostic factors have been identified for such
      hemorrhagic deaths, including poor performance status, high white blood cell
      (WBC) count and coagulopathy. Occurrence of thrombosis during treatment with ATRA
      may be associated with differentiation syndrome (DS) or represent an isolated
      event. Some prognostic factors have been reported to be associated with
      thrombosis, including increased WBC or aberrant immunophenotype of leukemic
      promyelocytes. Aim of this review is to report the incidence, severity, possible
      pathogenesis and clinical manifestations of thrombo-haemorrhagic deaths in APL.

PMID- 24862131
TI  - Complement the hemostatic system: an intimate relationship.
AB  - The complement system is important part of our innate immune system and interacts
      directly with the hemostatic system. Disorders of complement activation or
      dysregulation resulting in excess complement generation, such as Paroxysmal
      Nocturnal Hemoglobinuria (PNH), atypical Hemolytic uremic Syndrome (aHUS) and
      antiphospholipid syndrome (APLS) have been associated with significant
      thrombophilia. Terminal Complement (C5b-9) deposition on endothelial and tumor
      cell membranes has also been reported in a variety of cancer. Recent developments
      in complement inhibition have given us new insights into the mechanism of
      thrombosis in these disorders.

PMID- 24862133
TI  - New strategies of VTE prevention in cancer patients.
AB  - Venous thromboembolism (VTE) is a common complication in patients with cancer.
      VTE is a main cause of morbidity and mortality in patients with cancer and has a
      significant impact on their quality of life. Preventing VTE in cancer patients
      reduces both morbidity and mortality. The level of evidence for antithrombotic
      prophylaxis of VTE in patients with cancer varies for hospitalized and ambulatory
      patients. Hospitalized patients with active cancer (for both medical or surgical
      indication) and reduced mobility should receive thromboprophylaxis throughout
      hospital stay. Prophylaxis of VTE is not routinely recommended for outpatients
      with cancer on chemotherapy. For these patients, current guidelines suggest that
      clinicians should consider antithrombotic prophylaxis on a case-by-case basis in
      highly selected outpatients. Different strategies for identification of high-risk
      outpatients with cancer who could benefit of thromboprophylaxis are under
      consideration. The new oral anticoagulants could have a role for VTE prevention
      in ambulatory patients with cancer who are on chemotherapy, as they are
      administered at a fixed dose without routine laboratory monitoring and may have
      fewer drug interactions with anticancer agents.

PMID- 24862134
TI  - Heparins and cancer survival: where do we stand?
AB  - The relationship between cancer and thrombosis is a complex one with the
      haemostatic system and mechanisms of cancer growth and metastasis inextricably
      linked. The possibility that antithrombotics may confer a survival benefit on
      cancer patients has been considered for over sixty years, over which time a
      growing body of evidence has suggested that drugs such as low molecular weight
      heparins may inhibit cancer growth and metastasis through a myriad of mechanisms.
      Much of the trial data suggesting a survival benefit has been obtained through
      secondary subgroup analyses in highly heterogeneous populations. To date no
      sufficiently powered studies have been undertaken which support the routine use
      of LMWH to improve survival in cancer patients. This paper will review the
      current evidence around the topic to identify where we currently stand in this
      exciting yet challenging field.

PMID- 24862132
TI  - Guidelines for treatment and prevention of venous thromboembolism among patients
      with cancer.
AB  - The association between cancer and thrombosis has been recognized for more than
      150 years. Not only are patients with cancer at a substantially increased risk of
      developing venous thromboembolism (VTE), the link between several coagulation
      factors and tumor growth, invasion, and the development of metastases has been
      established. Reported rates of VTE in patients with cancer have increased in
      recent years likely reflecting, in part, improved diagnosis with sophisticated
      imaging techniques as well as the impact of more aggressive cancer diagnosis,
      staging, and treatment. Various therapeutic interventions, such as surgery,
      chemotherapy, hormonal therapy, targeted therapeutic strategies as well as the
      frequent use of indwelling catheters and other invasive procedures also place
      cancer patients at increased risk of VTE. The increasing risk of VTE, the
      multitude of risk factors, and the greater risk of VTE recurrence and death among
      patients with cancer represent considerable challenges in modern clinical
      oncology. The American Society of Clinical Oncology (ASCO) originally developed
      guidelines for VTE in patients with cancer in 2007. ASCO recently updated
      clinical practice guidelines on the treatment and prevention of VTE in patients
      with cancer following an extensive systematic review of the literature. Revised
      2013 guidelines have now been presented and will be discussed in this review.
      Although several new studies were identified and considered, many important
      questions remain regarding the relationship between thrombosis and cancer and the
      optimal care of patients at risk for VTE.

PMID- 24862136
TI  - Mechanistic explanation for platelet contribution to cancer metastasis.
AB  - Cancer-associated mortality is frequently caused by metastasis, however, our
      understanding of this process remains incomplete and therapeutic options are
      limited. Metastasis is a dynamic multi-step process involving intravasation of
      tumor cells into the host's blood and lymphatic vessels, their dissemination
      within the circulation, and finally arrest and extravasation in a distant organ
      where they establish secondary tumors. It is generally conceived that platelets
      contribute to all steps of hematogenous tumor dissemination. In this review, we
      provide an overview of the current knowledge of the platelet receptors involved
      in tumor cell-induced platelet aggregation, an essential immune surveillance
      escape mechanism of circulating tumor cells. We discuss how platelets prevent
      immunological attack, contribute to tumor cell extravasation and thereby
      facilitate colonization of distant organs.

PMID- 24862135
TI  - Insights into platelet-based control of coagulation.
AB  - The coagulation process is activated by tight control mechanisms, in which
      platelets play prominent and unique roles. In thrombosis and hemostasis,
      activated platelets regulate the coagulation system in various ways: by exposing
      a phosphatidylserine surface for thrombin formation, by supporting fibrin
      formation, and by regulating the retraction of a fibrin clot. In this review we
      discuss the involvement of platelet receptors, other membrane proteins,
      downstream signaling proteins, cytoskeleton-linked proteins and plasma proteins
      in these procoagulant functions. Studies with both genetically modified mice and
      pharmacological inhibitors indicate that, for collagen-adhered platelets, in part
      common signaling pathways lead to phosphatidylserine exposure, generation of
      thrombin and fibrin, and retraction of the fibrin clot. However, prolonged Ca(2+)
      elevation leads to thrombin generation, whereas integrin-dependent signaling
      stimulates fibrin clot retraction. Contact-dependent signaling pathways,
      triggered by homotypic platelet-platelet interactions, act in particular via the
      integrin route.

PMID- 24862137
TI  - Potential antidotes for reversal of old and new oral anticoagulants.
AB  - The prescription of new oral anticoagulants is on the rise. As opposed to vitamin
      K antagonists and heparins the new agents have single targets in the coagulation
      cascade, more predictable pharmacokinetics and they lack validated and available
      antidotes. In general, the new agents have similar or lower bleeding risk than
      vitamin K antagonists, especially risk of intracranial bleeding. Risk factors for
      bleeding are typically the same for old and new anticoagulants. Old age, renal
      dysfunction and concomitant antiplatelet agents seem to be recurring risk
      factors. Adequate supportive care and temporary removal of all antithrombotic
      agents constitute the basis for management of serious bleeding complications.
      With the exception of vitamin K (for vitamin K antagonists) and protamine (for
      heparin) the same array of prohemostatic agents--unactivated or activated
      prothrombin complex concentrate, and activated factor VIIa--have been tried for
      almost all anticocoagulants in different models, and for some agents also in
      patients, with varying success. Hemodialysis can reduce the level of dabigatran
      efficiently and activated charcoal may be used for very recent oral ingestion of
      lipophilic agents. In view of the shorter half life of the new agents compared to
      warfarin the need for reversal agents may be less critical. Nevertheless, highly
      specific reversal agents for the thrombin- and factor Xa-inhibitors are under
      development and might be available within two years.

PMID- 24862138
TI  - Treatment of cancer-associated thrombosis: perspectives on the use of novel oral
      anticoagulants.
AB  - Therapeutic options for the management of venous thromboembolism have expanded
      with the introduction of novel oral anticoagulants (NOACs). These agents offer
      significant advantages in convenience and simplicity, and large, well-designed
      clinical trials have shown that NOACs are comparable in efficacy and safety to
      traditional therapy using low molecular weight heparin (LMWH) followed by a
      vitamin K antagonist in most patients with deep vein thrombosis or pulmonary
      embolism. However, these results cannot be extrapolated to the general oncology
      population because randomized clinical trials have included very few and highly
      selected patients with cancer. Furthermore, how well these agents perform in
      comparison to LMWH, the drug of choice for both initial and long-term treatment
      of cancer-associated thrombosis, has not been evaluated. Other limitations of
      particular importance to patients with cancer, such as chemotherapy interaction,
      renal impairment, or hepatic involvement with metastases also need to be
      carefully considered because these patients have higher risks of recurrent
      thrombosis and bleeding. The use of NOACs is currently not recommended by
      international consensus guidelines but is now being explored in ongoing clinical
      trials. The results are eagerly awaited.

PMID- 24862139
TI  - Predicting recurrent venous thromboembolism in cancer: is it possible?
AB  - The association between cancer and venous thromboembolism (VTE) is well
      established. Many clinical and laboratory risk factors of a first cancer
      associated VTE have been identified. In contrast, the pathogenesis of recurrent
      VTE in cancer patients is less well studied. There is only very limited
      information on the importance of clinical risk factors and the role of biomarkers
      in this context has never been studied. Patients with cancer-associated VTE
      usually receive low-molecular-weight heparin for at least 3 to 6 months.
      Nevertheless, the recurrence risk during anticoagulation is as high as 10% and
      treatment-related major bleeding is more common in cancer-patient than in non
      cancer patients. Thus improvement of current treatment concepts is warranted. One
      important step to achieve this task is developing strategies that allow
      distinguishing patients with a high risk of recurrent VTE (who may benefit from
      prolonged or even intensified anticoagulation) from those with a low risk (i.e.
      patients in whom a shorter period of anticoagulant treatment at lower dose may be
      sufficient). Recently, a risk assessment model (RAM) for predicting recurrent VTE
      has been presented. By combining 4 clinical patient characteristics (sex, cancer
      type and stage, history of VTE), the Ottawa score allows stratification of cancer
      patients according to their VTE recurrence risk. The prediction tool was
      successfully validated in more than 800 patients from 2 prospective VTE treatment
      studies. Before this RAM can be introduced into routine clinical practice,
      however, management studies and impact analyses are required.

PMID- 24862140
TI  - Cancer-associated unsuspected pulmonary embolism.
AB  - Clinically unsuspected pulmonary embolism (UPE) is frequently diagnosed in cancer
      patients undergoing routine computed tomography scans for staging purposes or
      treatment response evaluation. The reported incidence of UPE ranges from 1% to 5%
      which probably represents an underestimation. A significant proportion of cancer
      patients with UPE actually do have pulmonary embolism (PE) related symptoms.
      However, these can erroneously be attributed to the cancer itself or to cancer
      therapy leading to a delayed or missed diagnosis. The incidence of UPE is likely
      to increase further with the improvements of imaging techniques. Radiologic
      features of UPE appear similar to symptomatic PE with nearly half of the UPE
      located in central pulmonary arteries and one third involving both lungs. UPE in
      cancer patients is not a benign condition with rates of recurrent venous
      thromboembolic events, bleeding and a mortality rate comparable to cancer
      patients with symptomatic PE. Current guidelines suggest that UPE should receive
      similar initial and long-term anticoagulant treatment as for symptomatic PE.
      However, direct evidence regarding the treatment of UPE is scarce and treatment
      indications are largely derived from studies performed in cancer patients with
      symptomatic venous thromboembolism. Selected subgroups of cancer patients with
      UPE such as those with sub-segmental UPE may be treated conservatively by
      withholding anticoagulation and avoiding the associated bleeding risk, although
      this requires further evaluation.

PMID- 24862141
TI  - Lymphoma and venous thromboembolism: influence on mortality.
AB  - BACKGROUND: The population-based incidence of acute venous thromboembolism (VTE)
      in adult patients diagnosed with non-Hodgkin's lymphoma has not been established,
      and the effect of VTE on survival is not clear. AIM: To determine the incidence
      of acute VTE in California residents diagnosed with lymphoma, and to determine
      the effect of acute VTE on survival. METHODS: We used the California Cancer
      Registry coupled with the California Patient Discharge database to identify
      incident cases with lymphoma, 1991-1997, and the incidence of first-time VTE in
      these patients. Multivariable models were constructed to evaluate risk of
      developing acute VTE within 2 years, and a proportional hazard model was used to
      predict death within 2 years, using acute VTE as a time-dependent covariate.
      RESULTS: There were 16,755 patients diagnosed with non-Hodgkin's lymphoma; 29%
      had low-grade, 66% intermediate/aggressive grade and 5.6% had high-grade
      lymphoma. Acute VTE developed in 3.6% of the patients by year 1 and 4.0% by the
      end of year 2. Significant predictors of acute VTE included advanced stage
      lymphoma, number of chronic comorbidities and advancing age. Significant
      predictors of death within 2 years included diagnosis of acute VTE, advanced
      stage disease, increasing number of co-morbidities, age over 75 years and
      intermediate or high grade histopathology. The effect of acute VTE on death
      increased as the time between lymphoma diagnosis and VTE diagnosis increased
      (HR=1.7 95%CI:1.5-1.9 for VTEs <6 months; HR=6.5 95%CI:4.7-8.9 VTEs 12-24
      months). CONCLUSIONS: Acute VTE developed frequently in patients with lymphoma,
      and VTE was a strong predictor of decreased survival.

PMID- 24862143
TI  - Risk stratification strategies for cancer-associated thrombosis: an update.
AB  - Rates of venous thromboembolism (VTE) vary substantially between cancer patients.
      Multiple clinical risk factors including primary site of cancer and systemic
      therapy, and biomarkers including leukocyte and platelet counts and tissue factor
      are associated with increased risk of VTE. However, risk cannot be reliably
      predicted based on single risk factors or biomarkers. New American Society of
      Clinical Guidelines recommend that patients with cancer be assessed for VTE risk
      at the time of chemotherapy initiation and periodically thereafter. This
      narrative review provides an update on risk stratification approaches including a
      validated Risk Score. Potential applications of risk assessment including
      targeted thromboprophylaxis are outlined. (c) 2014 Elsevier Ltd. All rights
      reserved. 

PMID- 24862144
TI  - Risk factors for venous thromboembolism in cancer: novel findings from the Vienna
      Cancer and Thrombosis Study (CATS).
AB  - Venous thromboembolism (VTE) occurs frequently in patients with cancer and
      contributes to elevated morbidity and mortality. Risk factors for the occurrence
      of VTE events in patients with cancer have been investigated in numerous clinical
      studies. For now more than 10 years, the Vienna Cancer and Thrombosis Study
      (CATS) has focused on the identification of parameters predictive of future VTE
      occurrence. CATS has contributed to new findings, which may help identify
      patients at high risk of developing VTE, by means of biomarkers (such as D-dimer,
      prothrombin fragment 1+2, soluble P-selectin, platelet count, coagulation factor
      VIII activity, thrombin generation potential, etc.). The association of tissue
      factor bearing microparticles and the mean platelet volume with the risk of VTE
      was also elaborately investigated in the framework of CATS. More recently CATS
      has researched clinical and clinicopathologic parameters which contribute to
      identification of patients at risk of VTE. The type of cancer is one of the most
      important risk factor for VTE occurrence. Also the stage of cancer and the
      histological grade of a tumor have been found to be associated with the
      occurrence of cancer-related VTE. In further investigations, venous diseases
      including a history of previous VTE, a history of superficial thrombophlebitis
      and the presence of varicose veins, have been associated with the risk of VTE in
      CATS.

PMID- 24862145
TI  - Unconventional approaches to the prevention of cancer associated thrombosis.
AB  - A number of strategies are currently under investigation to prevent venous
      thromboembolic events in cancer cohorts. Based on the efficacy of low molecular
      weight heparin in the treatment of thrombosis in cancer patients, a number of
      clinical studies have focused on evaluating the efficacy the low molecular weight
      heparins in the primary thromboprophylaxis setting. Further refinements in
      defining which cancer cohorts are at greatest risk of suffering thromboembolic
      events are under investigation such as clinical-laboratory risk scores and
      biomarkers such as tissue factor-bearing microparticles. However, alternative
      approaches to primary thromboprophylaxis beyond standard anticoagulants are also
      being evaluated in the clinic such anti-platelet agents, statins to reduce
      circulating tissue factor, and scheduled monitoring for venous thromboembolic
      events without pharmacologic thromboprophylaxis. In addition, clinical studies
      are underway to evaluate the antithrombotic efficacy of targeting extracellular
      protein disulfide isomerase with oral flavonoids (e.g. quercetin and
      isoquercetin). Emerging data regarding these unconventional approaches in the
      prevention of thromboembolic events in cancer patients is reviewed.

PMID- 24862146
TI  - Bleeding complications during anticoagulant treatment in patients with cancer.
AB  - Patients with cancer have an increased risk of bleeding complications, of which
      some are fatal. This risk is influenced by chemotherapy, cancer type and stage,
      thrombocytopenia, renal function, and previous bleeding. Since many cancer
      patients receive anticoagulant treatment for prophylaxis or treatment of venous
      thromboembolism (VTE), bleeding complications are a challenge in clinical
      practice. This review article focuses on the overall bleeding risk of cancer
      patients and the risk of major and clinically relevant bleeding associated with
      anticoagulant treatment, such as vitamin K antagonists, LMWH and the direct oral
      anticoagulants. It also describes strategies for individual risk assessments.

PMID- 24862147
TI  - Supportive transfusion therapy in cancer patients with acquired defects of
      hemostasis.
AB  - Bleeding occurs in approximately 10% of patients with cancer: supportive
      transfusion therapy with Platelets Concentrates (PC), Fresh Frozen Plasma (FFP)
      and plasma-derived or recombinant concentrates is often required for the
      cessation and prevention of the bleeding episodes. The most frequent causes of
      bleeding in cancer is thrombocytopenia followed by liver insufficiency with or
      without vitamin K deficiency, disseminated intravascular coagulation (DIC) and
      the inappropriate or excessive use of anticoagulants. Other acquired hemostatic
      defects such as acquired hemophilia (AHA) and acquired von Willebrand syndrome
      (AVWS) are rare but they can be life-threatening. Thrombocytopenia in cancer
      patients may be the consequence of marrow invasion, chemotherapy or platelet auto
      antibodies; patients with severe hypoproliferative thrombocytopenia, must be
      treated with PC and carefully followed to assess refractoriness to PC. The
      management of the other acquired defects of hemostasis usually requires the use
      of FFP and specific plasma-derived or recombinant concentrates. PC, FFP and
      plasma-derived concentrates can induce complications and/or adverse events in
      cancer patients: these include mainly allergic (ALR) or anaphylactic reactions
      (ANR), Transfusion-Associated Graft-Versus-Host Disease (TA-GVHD), Trasfusion
      transmitted bacteriemia (TTB), Transfusion-Related Acute Lung Injury (TRALI),
      Acute Hemolytic Transfusion Reactions (AHTR), Febrile Non Hemolytic Transfusion
      Reactions (FNHTR). Therefore, modifications such as leukocyte-reduction and
      irradiation of the blood components to be transfused in cancer patients are
      recommended to reduce the risk of these complications.

PMID- 24862142
TI  - Influence of recent immobilization or surgery on mortality in cancer patients
      with venous thromboembolism.
AB  - BACKGROUND: The influence of recent immobilization or surgery on mortality in
      cancer patients with venous thromboembolism (VTE) has not been thoroughly
      studied. METHODS: We used the RIETE Registry data to compare the 3-month
      mortality rate in cancer patients with VTE, with patients categorized according
      to the presence of recent immobilization, surgery or neither. The major outcomes
      were fatal pulmonary embolism (PE) and fatal bleeding within the first 3 months.
      RESULTS: Of 6,746 patients with active cancer and acute VTE, 1,224 (18%) had
      recent immobilization, 1,055 (16%) recent surgery, and 4,467 (66%) had neither.
      The all-cause mortality was 23.4% (95% CI: 22.4-24.5), and the PE-related
      mortality: 2.5% (95% CI: 2.1-2.9). Four in every ten patients dying of PE had
      recent immobilization (37%) or surgery (5.4%). Only 28% of patients with
      immobilization had received prophylaxis, as compared with 67% of the surgical.
      Fatal PE was more common in patients with recent immobilization (5.0%; 95% CI:
      3.9-6.3) than in those with surgery (0.8%; 95% CI: 0.4-1.6) or neither (2.2%; 95%
      CI: 1.8-2.6). On multivariate analysis, patients with immobilization were at an
      increased risk for fatal PE (odds ratio: 1.8; 95% CI: 1.2-2.5). CONCLUSIONS: One
      in every three cancer patients dying of PE had recent immobilization for >= 4
      days. Many of these deaths could have been prevented with adequate
      thromboprophylaxis.

PMID- 24862148
TI  - Thrombocytopenia in cancer patients.
AB  - Thrombocytopenia is a frequent complication of cancer and its treatment. The
      causes of thrombocytopenia in cancer patients can be diverse and multifactorial.
      Systemic chemotherapy is the most frequent cause of thrombocytopenia. The degree
      and duration thrombocytopenia depends upon whether the chemotherapeutic treatment
      is myeloablative, as used in stem cell transplants, or non-myeloablative, as
      typically used in solid non-hematologic malignancies. Additional causes of
      significant thrombocytopenia include tumor involvement of bone marrow and spleen;
      microangiopathic disorders such as disseminated intravascular coagulation,
      thrombotic thrombocytopenic purpura or hemolytic uremia syndrome.
      Lymphoproliferative malignancies can also be associated with secondary immune
      thrombocytopenia. Due to the broad differential diagnosis associated with cancer
      related thrombocytopenia, a careful diagnostic evaluation is indicated. The goal
      of treatment should be to maintain a safe platelet count to allow effective
      treatment of the underlying malignancy, prevent bleeding complications and to
      minimize the use of platelet product transfusion.

PMID- 24862149
TI  - Cancer-related coagulopathies.
AB  - The association between cancer and thrombosis is known for years. Besides the
      well-recognized connection between venous thromboembolism and malignancies, there
      are, however, also other manifestations of cancer-related activation of
      coagulation and (micro)vascular dysfunction. In fact, coagulation derangements
      and vascular disturbances in patients with cancer cover a wide spectrum of
      diseases and various clinical manifestations. In this review we will highlight
      the mechanisms that play a role in the systemic activation of coagulation in
      cancer patients, in its most severe form manifested as disseminated intravascular
      coagulation. Clinically, disseminated intravascular coagulation (DIC) in cancer
      has in general a less fulminant presentation than the types of DIC complicating
      sepsis and trauma. A more gradual, but also more chronic, systemic activation of
      coagulation can proceed subclinically. The relationship between venous
      thromboembolism and cancer as a consequence of the hypercoagulability will be
      discussed as well. Furthermore, the role of perturbed endothelium in the
      pathogenesis of microvascular dysfunction and microangiopathy in particular in
      the setting of cancer and chemo- or radiotherapy will be reviewed.

PMID- 24862150
TI  - Effects of tumor-expressed coagulation factors on cancer progression and venous
      thrombosis: is there a key factor?
AB  - Since the 19(th) century an association between cancer and thromboembolic events
      has been described, with a poorer survival prognosis. Production and secretion of
      procoagulant factors affect tumor biology and cancer-associated thrombosis.
      Tissue factor (TF) exerts coagulant and protease activated receptor (PAR)
      dependent signaling effects, both of which can contribute to tumor progression.
      Tumor cells are also capable of shedding TF-positive microparticles, suggesting a
      contribution to cancer-associated thrombosis at a distance from the tumor.
      Selected tumors are capable of ectopically expressing FVII and/or FX, which may
      lead to increased procoagulant features of tumors. Alternatively spliced TF
      (asTF) may affect tumor progression by inducing tumor growth and angiogenesis in
      an integrin dependent manner. Ectopic thrombin production also affects tumor
      progression by influencing proliferation rate, angiogenesis, invasion and
      metastasis. However, the roles of these coagulation factors in tumor progression
      and cancer-associated thrombosis are still not fully understood. In this review
      we will discuss several coagulation factors and their contribution on cancer
      progression and venous thromboembolism.

PMID- 24862152
TI  - Heparanase multiple effects in cancer.
AB  - Heparanase is an endo-beta-D-glucuronidase that is capable of cleaving heparan
      sulfate side chains of heparan sulfate proteoglycans on cell surfaces and the
      extracellular matrix, activity that is strongly implicated in tumor metastasis
      and angiogenesis. Apart of its well characterized enzymatic activity, heparanase
      was noted to exert also enzymatic-independent functions. Among these are the up
      regulation of vascular endothelial growth factor (VEGF)-A, VEGF-C and activation
      of intra-cellular signaling involved in cell survival and proliferation. We had
      earlier demonstrated that heparanase may also affect the hemostatic system in a
      non-enzymatic manner. We had shown that heparanase up-regulated the expression of
      the blood coagulation initiator- tissue factor (TF) and interacted with the
      tissue factor pathway inhibitor (TFPI) on the cell surface membrane of
      endothelial and tumor cells, leading to dissociation of TFPI and resulting in
      increased cell surface coagulation activity. Moreover, we have demonstrated that
      heparanase directly enhanced TF activity which led to increased factor Xa
      production and subsequent activation of the coagulation system. Taking into
      account the prometastatic, pro-angiogenic and pro-coagulant functions of
      heparanase, over-expression in human malignancies and abundance in platelets,
      implies that heparanase is potentially a good target for cancer therapy.

PMID- 24862153
TI  - Glycosaminoglycans in cancer treatment.
AB  - Studies aimed at the identification of biomarkers and treatment targets of cancer
      have focused on mRNAs, miRNAs, and proteins expressed by malignant cells, while
      glycoproteins mainly produced by stromal cells remain relatively unexplored.
      Glycans lack a given template for their biosynthesis that involves the concerted
      action of several, sometimes >15 different enzymes. This fact complicates the
      analysis at the genomic level of the role of glycoproteins in clinical oncology.
      The glycosaminoglycans (GAGs) stand out as highly polyanionic components at the
      surface of malignant and stromal tumor cells as well as their surrounding matrix.
      Published data thus describe a multifaceted regulatory role of GAGs and GAG
      conjugated proteins, proteoglycans, in e.g. tumor associated angiogenesis,
      coagulation, invasion, and metastasis. Relatively small, randomized clinical
      trials suggest that heparin, an over-sulfated variant of the GAG heparan sulfate,
      may have direct, anti-tumor effects. Several ongoing trials aim at establishing
      whether heparin and its derivatives should be added to standard treatment of
      cancer patients or not, based on progression free- and overall survival end-point
      data. Given the potential bleeding complications with this treatment, other
      strategies to block GAG function should provide interesting alternatives. In the
      emerging era of personalized medicine, one can foresee the development of
      predictive biomarkers to select patients that may benefit from GAG-targeted
      treatments, aiming at individualized prevention of thromboembolic complications
      as well as inhibition of tumor development and progression. Here, the role of
      GAGs as targets and vehicles of cancer treatment is discussed with special
      emphasis on angiogenesis and coagulation associated mechanisms.

PMID- 24862151
TI  - Role of the protein C receptor in cancer progression.
AB  - The hemostatic system plays pleiotropic roles in cancer progression by shaping
      the tumor microenvironment and metastatic niches through thrombin-dependent
      fibrin deposition and platelet activation. Expanding experimental evidence
      implicates coagulation protease receptors expressed by tumor cells as additional
      players that directly influence tumor biology. Pro-angiogenic G protein-coupled
      signaling of TF through protease activated receptor 2 and regulation of tumor
      cell and vascular integrins through ligation by alternative spliced TF are
      established pathways driving tumor progression. Our recent work shows that the
      endothelial protein C receptor (EPCR), a stem cell marker in hematopoietic,
      neuronal and epithelial cells, is also crucial for breast cancer growth in the
      orthotopic microenvironment of the mammary gland. In aggressive triple-negative
      breast cancer cells, EPCR expression is a characteristic of cancer stem cell-like
      populations that have tumor initiating properties in vivo. Blocking antibodies to
      EPCR attenuate in vivo tumor growth and proliferation specifically of EPCR(+)
      cells on defined integrin matrices in vitro. We also showed that tumor-associated
      macrophages are a source for upstream coagulation proteases that can activate TF-
      and EPCR-dependent cellular responses, suggesting that tumor cells utilize the
      tumor microenvironment for tumor promoting coagulation protease signaling.

PMID- 24862154
TI  - Different roles suggested by sex-biased expression and pheromone binding affinity
      among three pheromone binding proteins in the pink rice borer, Sesamia inferens
      (Walker) (Lepidoptera: Noctuidae).
AB  - Pheromone binding proteins (PBPs) are thought to bind and transport hydrophobic
      sex pheromone molecules across the aqueous sensillar lymph to specific pheromone
      receptors on the dendritic membrane of olfactory neurons. A maximum of 3 PBP
      genes have been consistently identified in noctuid species, and each of them
      shares high identity with its counterparts in other species within the family.
      The functionality differences of the 3 proteins are poorly understood. In the
      present study, 3 PBP cDNAs (SinfPBP1, 2, 3) were identified from the pink rice
      borer, Sesamia inferens, for the first time. The quantitative real-time PCR
      indicated that the 3 PBPs displayed similar temporal but very different sex
      related expression profiles. Expression of SinfPBP1 and SinfPBP2 were highly and
      moderately male biased, respectively, while SinfPBP3 was slightly female biased,
      as SinfPBPs were expressed at very different levels (PBP1>PBP2?PBP3) in male
      antennae, but at similar levels in female antennae. Furthermore, the 3 SinfPBPs
      displayed different ligand binding profiles in fluorescence competitive binding
      assays. SinfPBP1 exhibited high and similar binding affinities to all 3 sex
      pheromone components (Ki=0.72-1.60 MUM), while SinfPBP2 showed selective binding
      to the alcohol and aldehyde components (Ki=0.78-1.71 MUM), and SinfPBP3 showed no
      obvious binding to the 3 sex pheromone components. The results suggest that
      SinfPBP1 plays a major role in the reception of female sex pheromones in S.
      inferens, while SinfPBP3 plays a least role (if any) and SinfPBP2 functions as a
      recognizer of alcohol and aldehyde components.

PMID- 24862155
TI  - Locusts increase carbohydrate consumption to protect against a fungal
      biopesticide.
AB  - There is growing evidence to suggest that hosts can alter their dietary intake to
      recoup the specific resources involved in mounting effective resistance against
      parasites and pathogens. We examined macronutrient ingestion and disease
      resistance in the Australian plague locust (Chortoicetes terminifera), challenged
      with a fungal pathogen (Metarhizium acridum) under dietary regimes varying in
      their relative amounts of protein and digestible carbohydrate. Dietary protein
      influenced constitutive immune function to a greater extent than did
      carbohydrate, indicating higher protein costs of mounting an immune defence than
      carbohydrate or overall energy costs. However, it appears that increased immune
      function, as a result of greater protein ingestion, was not sufficient to protect
      locusts from fungal disease. We found that locusts restricted to diets high in
      protein (P) and low in carbohydrate (C) were more likely to die of a fungal
      infection than those restricted to diets with a low P:C ratio. We hypothesise
      that the fungus is more efficient at exploiting protein in the insect's
      haemolymph than the host is at producing immune effectors, tipping the balance in
      favour of the pathogen on high-protein diets. When allowed free-choice, survivors
      of a fungus-challenge chose a less-protein-rich diet than those succumbing to
      infection and those not challenged with fungus locusts. These results are
      contrary to previous studies on caterpillars in the genus Spodoptera challenged
      with bacterial and baculoviral pathogens, indicating that nutrient ingestion and
      pathogen resistance may be a complex interaction specific to different host
      species and disease agents. 

PMID- 24862156
TI  - Towards an integrated understanding of gut microbiota using insects as model
      systems.
AB  - Metazoans form symbioses with microorganisms that synthesize essential
      nutritional compounds and increase their efficiency to digest and absorb
      nutrients. Despite the growing awareness that microbes within the gut play key
      roles in metabolism, health and development of metazoans, symbiotic relationships
      within the gut are far from fully understood. Insects, which generally harbor a
      lower microbial diversity than vertebrates, have recently emerged as potential
      model systems to study these interactions. In this review, we give a brief
      overview of the characteristics of the gut microbiota in insects in terms of low
      diversity but high variability at intra- and interspecific levels and we
      investigate some of the ecological and methodological factors that might explain
      such variability. We then emphasize how studies integrating an array of
      techniques and disciplines have the potential to provide new understanding of the
      biology of this micro eco-system. 

PMID- 24862157
TI  - The effects of forced-egg retention on the blood-feeding behavior and
      reproductive potential of Culex pipiens (Diptera: Culicidae).
AB  - High rates of West Nile virus (WNV) transmission to humans are associated with
      exceptionally hot and dry summers. This is paradoxical since the eggs of Culex
      vectors of WNV depend on the persistence of containers with water, which decline
      during droughts. We examined the effects of forced-egg retention on the
      reproductive success of female Culex pipiens as well as behavioral responses,
      such as likelihood of secondary blood meals. As controls we examined the effects
      of female age and delayed mating. We found that early mating is essential to
      achieve reproductive success and, consistent with an "all-or-none" ovipositing
      strategy, C. pipiens females are able to retain considerable reproductive
      potential while searching for oviposition sites. Specifically, although forced
      egg retention resulted in significant decreases in fitness, the decline was
      moderate for 5 weeks and most can be accounted for by increases in female age.
      Consequently, no females took blood more than once per gonotrophic cycle, which
      eliminates the possibility that heightened vectorial capacity due to multiple
      blood-feedings increases WNV transmission during periods of drought. Instead, our
      findings suggest that during droughts populations of C. pipiens have time to
      locate the remaining water holes, which are associated with human populations and
      WNV-competent bird species.

PMID- 24862158
TI  - Baroreflex sensitivity: reliability of baroreflex components of the Valsalva
      maneuver.
AB  - The reliability of the baroreflex sensitivity measurement has not yet been
      established. Thus, the objective of this study was to define intra-rater
      reliability of baroreflex sensitivity (BRS) measurements of the Valsalva maneuver
      (VM) in healthy individuals. Twenty-two healthy volunteers underwent VM testing
      at two time points. Intra-rater reliability was determined by the intra-class
      correlation coefficient (ICC), standard error of measurement and minimal
      detectable difference. Vagal BRS showed good reliability (ICC=0.84), while
      alternative adrenergic BRS was moderately reproducible (ICC=0.61). Vagal and
      alternative adrenergic components of BRS in VM are reliable measurements. 

PMID- 24862159
TI  - Highlights in basic autonomic neurosciences: Changes to the autonomic nervous
      system associated with healthy ageing.

PMID- 24862160
TI  - Highlights in clinical autonomic neurosciences: Brain volume and autonomic
      regulation.
AB  - Advances in volumetric magnetic resonance imaging (MRI) technology are beginning
      to provide structural correlates to functional dysautonomic syndromes in the
      brain. This paper highlights several interesting recent discoveries in which
      measurable variations in general or regional subcortical or cortical brain volume
      corresponded to changes in blood pressure or heart rate. Although these MRI
      findings currently lack diagnostic value in routine clinical practice, they may
      provide important clues to the pathophysiology of autonomic disorders and to
      links between autonomic and cognitive disorders. If validated by further studies,
      they also have potential implications for the management of orthostatic
      hypotension, particularly when combined with hypertension. 

PMID- 24862161
TI  - Development of a targeted metagenomic approach to study a genomic region involved
      in light harvesting in marine Synechococcus.
AB  - Synechococcus, one of the most abundant cyanobacteria in marine ecosystems,
      displays a broad pigment diversity. However, the in situ distribution of pigment
      types remains largely unknown. In this study, we combined flow cytometry cell
      sorting, whole-genome amplification, and fosmid library construction to target a
      genomic region involved in light-harvesting complex (phycobilisome) biosynthesis
      and regulation. Synechococcus community composition and relative contamination by
      heterotrophic bacteria were assessed at each step of the pipeline using terminal
      restriction fragment length polymorphism targeting the petB and 16S rRNA genes,
      respectively. This approach allowed us to control biases inherent to each method
      and select reliable WGA products to construct a fosmid library from a natural
      sample collected off Roscoff (France). Sequencing of 25 fosmids containing the
      targeted region led to the assembly of whole or partial phycobilisome regions.
      Most contigs were assigned to clades I and IV consistent with the known dominance
      of these clades in temperate coastal waters. However, one of the fosmids
      contained genes distantly related to their orthologs in reference genomes,
      suggesting that it belonged to a novel phylogenetic clade. Altogether, this study
      provides novel insights into Synechococcus community structure and pigment type
      diversity at a representative coastal station of the English Channel. 

PMID- 24862162
TI  - Improving lithium-sulphur batteries through spatial control of sulphur species
      deposition on a hybrid electrode surface.
AB  - Lithium-sulphur batteries are attractive owing to their high theoretical energy
      density and reasonable kinetics. Despite the success of trapping soluble
      polysulphides in a matrix with high surface area, spatial control of solid-state
      sulphur and lithium sulphide species deposition as a critical aspect has not been
      demonstrated. Herein, we show a clear visual evidence that these solid species
      deposit preferentially onto tin-doped indium oxide instead of carbon during
      electrochemical charge/discharge of soluble polysuphides. To incorporate this
      concept of spatial control into more practical battery electrodes, we further
      prepare carbon nanofibers with tin-doped indium oxide nanoparticles decorating
      the surface as hybrid three-dimensional electrodes to maximize the number of
      deposition sites. With 12.5 MUl of 5 M Li2S8 as the catholyte and a rate of C/5,
      we can reach the theoretical limit of Li2S8 capacity ~?n1,470 mAh g(-1) (sulphur
      weight) under the loading of hybrid electrode only at 4.3 mg cm(-2).

PMID- 24862164
TI  - An aluminophosphate molecular sieve with 36 crystallographically distinct
      tetrahedral sites.
AB  - The structure of the new medium-pore aluminophosphate molecular sieve PST-6 is
      determined by the combined use of rotation electron diffraction tomography,
      synchrotron X-ray powder diffraction, and computer modeling. PST-6 was prepared
      by calcination of another new aluminophosphate material with an unknown structure
      synthesized using diethylamine as a structure-directing agent, which is thought
      to contain bridging hydroxy groups. PST-6 has 36 crystallographically distinct
      tetrahedral sites in the asymmetric unit and is thus crystallographically the
      most complex zeolitic structure ever solved. 

PMID- 24862163
TI  - Effects of calcium-modified titanium implant surfaces on platelet activation,
      clot formation, and osseointegration.
AB  - The clinical success of load bearing dental and orthopedic implants relies on
      adequate osseointegration. Because of its favorable properties, titanium is
      generally considered as the material of choice. Following implant placement,
      titanium surfaces establish an ionic equilibrium with the surrounding tissues in
      which calcium plays major roles. Calcium is a cofactor of the coagulation cascade
      that mediates plasma protein adsorption and intervenes in a number of other intra
      and extracellular processes relevant for bone regeneration. In this study,
      titanium surfaces were modified with calcium ions (Ca(2+) surfaces) and their
      responses to in vitro and in vivo models were analyzed. Unlike unmodified
      surfaces, Ca(2+) surfaces were superhydrophilic and induced surface clot
      formation, platelet adsorption and activation when exposed to blood plasma.
      Interestingly, in vivo osseointegration using a peri-implant gap model in rabbit
      demonstrated that Ca(2+) surfaces significantly improved peri-implant bone volume
      and density at 2 weeks and bone implant contact at 8 weeks as compared to the
      unmodified controls. The combination of Ca(2+) surfaces with plasma rich in
      growth factors produced significantly more bone contact already at 2 weeks of
      implantation. These findings suggest the importance of the provisional matrix
      formation on tissue integration and highlight the clinical potential of Ca(2+)
      titanium surfaces as efficient stimulators of implant osseointegration.

PMID- 24862165
TI  - Endothelin-1 increases the expression of VEGF-R1/Flt-1 receptors in rat cultured
      astrocytes through ETB receptors.
AB  - Expressions of vascular endothelial growth factor (VEGF) receptors in astrocytes
      are increased in damaged brains. To clarify the regulatory mechanisms of VEGF
      receptors, the effects of endothelin-1 (ET-1) were examined in rat cultured
      astrocytes. Expressions of VEGF-R1 and -R2 receptor mRNA were at similar levels,
      whereas the mRNA expressions of VEGF-R3 and Tie-2, a receptor for angiopoietins,
      were lower. Placenta growth factor, a selective agonist of the VEGF-R1 receptor,
      induced phosphorylation of focal adhesion kinase (FAK) and extracellular signal
      regulated kinase 1/2 (ERK1/2). Phosphorylations of FAK and ERK 1/2 were also
      stimulated by VEGF-E, a selective VEGF-R2 agonist. Increased phosphorylations of
      FAK and ERK1/2 by VEGF165 were reduced by selective antagonists for VEGF-R1 and 
      R2. Treatment with ET-1 increased VEGF-R1 mRNA and protein levels. The effects of
      ET-1 on VEGF-R1 mRNA were mimicked by Ala(1,3,11,15) -ET-1, a selective agonist
      for ETB receptors, and inhibited by BQ788, an ETB antagonist. ET-1 did not affect
      the mRNA levels of VEGF-R2, -R3, and Tie-2. Pre-treatment with ET-1 potentiated
      the effects of placenta growth factor on phosphorylations of FAK and ERK1/2.
      These findings suggest that ET-1 induces up-regulation of VEGF-R1 receptors in
      astrocytes, and potentiates VEGF signals in damaged nerve tissues. To clarify the
      regulatory mechanisms of vascular endothelial growth factor (VEGF) receptors, the
      effects of endothelin-1 (ET-1) were examined in rat cultured astrocytes. Effects
      of selective VEGF-R1 and R2 agonist showed that these receptors were linked to
      focal adhesion kinase (FAK) and extracellular signal regulated kinase 1/2
      (ERK1/2). Treatment with ET-1 increased expression of VEGF-R1, which was mediated
      by ETB receptors. Pre-treatment with ET-1 potentiated the VEGF-R1-mediated
      activations of FAK and ERK1/2. These findings suggest that ET-1 induces up
      regulation of VEGF-R1 receptors in astrocytes. 

PMID- 24862166
TI  - Using vaginal Group B Streptococcus colonisation in women with preterm premature
      rupture of membranes to guide the decision for immediate delivery: a secondary
      analysis of the PPROMEXIL trials.
AB  - OBJECTIVE: To investigate whether vaginal Group B Streptococcus (GBS)
      colonisation or other baseline characteristics of women with preterm premature
      rupture of membranes (PPROM) can help in identifying subgroups of women who would
      benefit from immediate delivery. DESIGN: Secondary analysis of the PPROMEXIL
      trials. SETTING: Sixty hospitals in the Netherlands. POPULATION: Women with PPROM
      between 34 and 37 weeks of gestation. METHODS: Random assignment of 723 women to
      immediate delivery or expectant management. MAIN OUTCOME MEASURES: Early onset
      neonatal sepsis. RESULTS: Vaginal GBS colonisation status was the only marker
      which was significantly associated with the benefit of immediate delivery (P for
      interaction: 0.04). GBS colonisation was observed in 14% of women. The risk of
      early onset neonatal sepsis in GBS-positive women was high (15.2%) when they were
      managed expectantly but this risk was reduced to 1.8% with immediate delivery.
      The early onset neonatal sepsis risk was much lower in neonates of GBS-negative
      women: 2.6% after expectant management and 2.9% with immediate delivery. We
      estimated that by inducing labour only in GBS-positive women, there would be a
      10.4% increase in term delivery rate, while keeping neonatal sepsis and caesarean
      delivery rates comparable to a strategy of labour induction for all. CONCLUSIONS:
      Our post hoc findings suggest that women with PROM between 34 and 37 weeks might
      benefit from immediate delivery if they have GBS vaginal colonisation, while in
      GBS-negative women labour induction could be delayed until 37 weeks.

PMID- 24862168
TI  - We want you back.

PMID- 24862167
TI  - Varenicline efficacy and safety among methadone maintained smokers: a randomized
      placebo-controlled trial.
AB  - AIMS: To test the efficacy and safety of varenicline as an aid to smoking
      cessation in methadone-maintained smokers. DESIGN: Multicenter, randomized,
      double-blind, placebo-controlled trial with random assignment to 12 weeks of
      varenicline 1 mg twice daily (n = 57) or matched placebo (n = 55), with in-person
      and telephone counseling. SETTING: Urban methadone programs in the Bronx, New
      York City, New York, USA. PARTICIPANTS: Methadone maintenance patients, smoking
      >=5 cigarettes/day, interested in quitting, stable in methadone treatment,
      without current Axis I psychiatric disorders, suicidal ideation or recent suicide
      attempts. MEASUREMENTS: Seven-day point prevalence abstinence verified by expired
      carbon monoxide (CO) < 8 parts per million at week 12 (primary outcome); carbon
      monoxide (CO)-verified abstinence, cigarettes/day, incident Axis I psychiatric
      illness, suicidal ideation or serious adverse events (SAEs) at weeks 2, 4, 8, 12
      or 24 (secondary outcomes). FINDINGS: Baseline demographic, smoking and clinical
      factors were similar between groups. Retention at 24 weeks was 90%. Subjects
      receiving varenicline were more likely than those receiving placebo to achieve
      abstinence (10.5 versus 0%, P = 0.03; effect size 10.5%, 95% confidence interval
      (CI) = 4.4-19.3%) and to reduce smoking (median five versus two cigarettes/day, P
      < 0.001) at 12 weeks. These effects were not maintained after drug treatment
      ceased. Incident psychiatric illness (OR= 0.84, 95% CI = 0.16, 4.4) and
      suicidality [odds ratio (OR) = 0.88, 95% CI 0.2, 3.9] were not different between
      groups. There were no psychiatric or cardiac SAEs. CONCLUSIONS: Varenicline can
      aid short-term smoking abstinence in methadone-maintained smokers.

PMID- 24862169
TI  - Can non-nutritive sweeteners enhance outcomes of weight loss interventions?

PMID- 24862170
TI  - The effects of water and non-nutritive sweetened beverages on weight loss during
      a 12-week weight loss treatment program.
AB  - OBJECTIVE: To compare the efficacy of non-nutritive sweetened beverages (NNS) or
      water for weight loss during a 12-week behavioral weight loss treatment program.
      METHODS: An equivalence trial design with water or NNS beverages as the main
      factor in a prospective randomized trial among 303 men and women was employed.
      All participants participated in a behavioral weight loss treatment program. The
      results of the weight loss phase (12 weeks) of an ongoing trial (1 year) that is
      also evaluating the effects of these two treatments on weight loss maintenance
      were reported. RESULTS: The two treatments were not equivalent with the NNS
      beverage treatment group losing significantly more weight compared to the water
      group (5.95 kg versus 4.09 kg; P < 0.0001) after 12 weeks. Participants in the
      NNS beverage group reported significantly greater reductions in subjective
      feelings of hunger than those in the water group during 12 weeks. CONCLUSION:
      These results show that water is not superior to NNS beverages for weight loss
      during a comprehensive behavioral weight loss program.

PMID- 24862173
TI  - Vacuum-assisted inferior vena cava thrombus removal using a percutaneous
      technique.
AB  - We report a patient with a massive inferior vena cava (IVC) thrombus requiring
      immediate intervention. The patient underwent successful thrombectomy using a
      percutaneous catheter aspiration system. Percutaneous removal of an IVC thrombus
      is a safe and effective treatment option for severely ill patients.

PMID- 24862172
TI  - Enhanced external counterpulsation improves endothelial function and exercise
      capacity in patients with ischaemic left ventricular dysfunction.
AB  - Enhanced external counterpulsation (EECP) therapy decreases angina episodes and
      improves quality of life in patients with left ventricular (LV) dysfunction
      (LVD). However, studies have not elucidated the mechanisms of action and overall
      effects of EECP in patients with LVD. The purpose of the present study was to
      investigate the effects of EECP on endothelial function in peripheral conduit
      arteries and exercise capacity (peak Vo2 ) in patients with LVD. Patients with
      ischaemic LVD (ejection fraction (EF) 34.5 +/- 4.2%; n = 9) and patients with
      symptomatic coronary artery disease (CAD) and preserved LV function (EF 53.5 +/-
      6.6%; n = 15) were studied before and after 35 sessions (1 h) of EECP. Brachial
      and femoral artery flow-mediated dilation (bFMD and fFMD, respectively) were
      evaluated using high-resolution ultrasound. Enhanced external counterpulsation
      elicited similar significant improvements in the following FMD parameters in the
      CAD and LVD groups (P >= 0.05 between groups for all): absolute bFMD (+53% and
      +70%, respectively), relative bFMD (+50% and +74%, respectively), bFMD normalized
      for shear rate (+70% and +61%, respectively), absolute fFMD (+33% and +21%,
      respectively) and relative fFMD (+32% and +17%, respectively). In addition, EECP
      significantly improved plasma levels of nitrate/nitrite (+55% and +28%) and
      prostacyclin (+50% and +70%), as well as peak Vo2 (+36% and +21%), similarly in
      both the CAD and LVD groups (P >= 0.05 between groups for all). Despite reduced
      LV function, EECP therapy significantly improves peripheral vascular function and
      functional capacity in CAD patients with ischaemic LVD to a similar degree to
      that seen in CAD patients with preserved LV function. 

PMID- 24862171
TI  - Amygdala task-evoked activity and task-free connectivity independently contribute
      to feelings of arousal.
AB  - Individual differences in the intensity of feelings of arousal while viewing
      emotional pictures have been associated with the magnitude of task-evoked blood
      oxygen dependent (BOLD) response in the amygdala. Recently, we reported that
      individual differences in feelings of arousal are associated with task-free
      (resting state) connectivity within the salience network. There has not yet been
      an investigation of whether these two types of functional magnetic resonance
      imaging (MRI) measures are redundant or independent in their relationships to
      behavior. Here we tested the hypothesis that a combination of task-evoked
      amygdala activation and task-free amygdala connectivity within the salience
      network relate to individual differences in feelings of arousal while viewing of
      negatively potent images. In 25 young adults, results revealed that greater task
      evoked amygdala activation and stronger task-free amygdala connectivity within
      the salience network each contributed independently to feelings of arousal,
      predicting a total of 45% of its variance. Individuals who had both increased
      task-evoked amygdala activation and stronger task-free amygdala connectivity
      within the salience network had the most heightened levels of arousal. Task
      evoked amygdala activation and task-free amygdala connectivity within the
      salience network were not related to each other, suggesting that resting-state
      and task-evoked dynamic brain imaging measures may provide independent and
      complementary information about affective experience, and likely other kinds of
      behaviors as well.

PMID- 24862174
TI  - Disaster medicine: genealogy of a concept.
AB  - This paper evaluates disaster medicine from a historical perspective that
      facilitates the understanding of its present. Today, disaster medicine and
      humanitarian medicine are inextricably linked and the terms are sometimes used
      synonymously. An in-depth analysis of an extensive body of concrete empirical
      cases from various sources (i.e. archival records) reveals, however, that they
      have not always been the same. A genealogical, history-of-knowledge approach
      demonstrates that the concept of disaster medicine emerged in the early 20th
      century in Switzerland in the context of industrialization. Even though it gained
      important impetus during the First World War, the concept was informed by the
      experiences of forensic physicians in technological disasters such as mining
      explosions. The Cold War constituted the historical constellation in which
      disaster medicine was developed in West Germany during the 1960s and 1970s in a
      way that was paradigmatic for other Western European countries. At the same time,
      it was contested there in an unusual, historically unique way. Although focusing
      on a Western European context, this paper explores how medical interventions in
      disasters were international events and how the practice of disaster medicine was
      developed and "trained" through being applied in the Global South. It
      demonstrates the historicity of disaster medicine's political character and of
      the controversies generated by its involvement in civil and military operations.
      Throughout the 20th century, the political nature and military involvement of
      disaster medicine resulted in a number of ethical and practical issues, which are
      similar to the challenges facing humanitarian medicine today. The exploration of
      disaster medicine's past can therefore open up critical interventions in
      humanitarian medicine's present. 

PMID- 24862176
TI  - Abstracts of the Joint Congress of European Neurology, 31 May-3 June, 2014,
      Istanbul, Turkey.

PMID- 24862175
TI  - Medical humanitarianism in the United States: alternative healthcare,
      spirituality and political advocacy in the case of Our Lady Guadalupe Free
      Clinic.
AB  - Exclusionary practices in dominant market-based systems are recognized as
      contributing to global health inequities. Undocumented immigrants are
      particularly vulnerable to unequal access to healthcare. Humanitarian NGOs strive
      to respond meaningfully to these health inequities among migrants and
      undocumented immigrants. Few studies describe the work of humanitarian NGOs that
      advocate for the right to health of undocumented immigrants in high-income
      countries. This paper discusses immigration, health, and human rights while
      examining solidarity, spirituality, and advocacy using a U.S.-based example of
      medical humanitarianism: the 'Our Lady of Guadalupe Free Clinic.' In 2011, the
      Free Clinic began in the basement of a Catholic parish in Minnesota in response
      to the lack of access to medical services for undocumented immigrants. Run by a
      local grassroots organization, it is held every six weeks and offers free primary
      healthcare to Latino immigrants and the uninsured. In this article, we examine
      the tricky relationship between humanitarianism and human rights in the U.S.
      Using ethnography, we draw on participant observation and interviews with 30
      clinic volunteers, including health professionals, administrators, language
      interpreters, and spiritual leaders. The study was conducted September 2012
      December 2013 in southern Minnesota. We examine how notions of solidarity,
      spirituality, and advocacy structure faith-based medical humanitarianism in the
      U.S. and explore the underlying tensions between the humanitarian mandate,
      spiritual teachings (social justice, solidarity), and political advocacy.
      Examining a moment of "crisis" in the Clinic, our study shows that volunteers
      experience the alliance between spirituality and advocacy with uneasiness. While
      a spiritual calling may initially motivate volunteers to serve, an embrace of
      human rights advocacy is important in a sustained effort to provide humanitarian
      medical care to individuals who fall outside of the political and moral community
      in the U.S. 

PMID- 24862177
TI  - Approach to overuse of herbal and dietary supplements: a teachable moment.

PMID- 24862178
TI  - Epidemiology of Achilles tendon ruptures: increasing incidence over a 33-year
      period.
AB  - We investigated the epidemiology of total Achilles tendon ruptures and
      complication rates after operative and nonoperative treatments over a 33-year
      period in Oulu, Finland. Patients with Achilles tendon ruptures from 1979 to 2011
      in Oulu were identified from hospital patient records. Demographic data,
      treatment method, and complications were collected retrospectively from medical
      records. Overall and sex- and age-specific incidence rates were calculated with
      95% confidence intervals (CIs). The overall incidence per 100,000 person-years
      increased from 2.1 (95% CI 0.3-7.7) in 1979 to 21.5 (95% CI 14.6-30.6) in 2011.
      The incidence increased in all age groups. The mean annual increase in incidence
      was 2.4% (95% CI 1.3-4.7) higher for non-sports-related ruptures than for sports
      related ruptures (P = 0.036). The incidence of sports-related ruptures increased
      during the second 11-year period whereas the incidence of non-sports-related
      ruptures increased steadily over the entire study period. Infection was four
      times more common after operative treatment compared with nonoperative treatment,
      re-rupture rates were similar. The incidence of Achilles tendon ruptures
      increased in all age groups over a 33-year period. Increases were mainly due to
      sports-related injuries in the second 11-year period and non-sports-related
      injuries in the last 11-year period.

PMID- 24862179
TI  - Development of extramedullary sites of leukaemia during ruxolitinib therapy for
      myelofibrosis.

PMID- 24862181
TI  - Prevention of type 2 diabetes among youth: a systematic review, implications for
      the school nurse.
AB  - Childhood obesity and the early development of type 2 diabetes (T2 DM) place
      students at risk for chronic health problems. The school nurse is uniquely
      situated to promote school health initiatives that influence health behavior. The
      purpose of this review was to determine effective nonpharmacological
      interventions for prevention of T2 DM in youth. Researchers from 35 reports
      modified T2 DM risk factors. These nonpharmacological interventions often include
      increasing daily activity, decreasing caloric intake, and increasing muscle mass.
      Some researchers also included psychological and social support interventions
      intended to strengthen initiating and/or maintaining health behavior.
      Characteristics of effective nonpharmacological T2 DM prevention interventions
      are discussed. Findings from this review are a useful guide for the
      implementation of T2 DM prevention strategies in the school setting. Few school
      based studies included high school students; therefore, further research is
      needed among older adolescents on the efficacy of nonpharmacological
      interventions in the high school. 

PMID- 24862180
TI  - Neuropilin-2 and its ligand VEGF-C predict treatment response after transurethral
      resection and radiochemotherapy in bladder cancer patients.
AB  - The standard treatment for invasive bladder cancer is radical cystectomy. In
      selected patients, bladder-sparing therapy can be performed by transurethral
      resection (TURBT) and radio-chemotherapy (RCT) or radiotherapy (RT). Our
      published in vitro data suggest that the Neuropilin-2 (NRP2)/VEGF-C axis plays a
      role in therapy resistance. Therefore, we studied the prognostic impact of NRP2
      and VEGF-C in 247 bladder cancer patients (cN0M0) treated with TURBT and RCT (n =
      198) or RT (n = 49) and a follow-up time up to 15 years. A tissue microarray was
      analyzed by immunohistochemistry. NRP2 expression emerged as a prognostic factor
      in overall survival (OS; HR: 3.42; 95% CI: 1.48 - 7.86; p = 0.004) and was
      associated with a 3.85-fold increased risk of an early cancer specific death (95%
      CI: 0.91 - 16.24; p = 0.066) in multivariate analyses. Cancer specific survival
      (CSS) dropped from 166 months to 85 months when NRP2 was highly expressed (p =
      0.037). Patients with high VEGF-C expression have a 2.29-fold increased risk of
      shorter CSS (95% CI: 1.03-5.35; p = 0.043) in univariate analysis. CSS dropped
      from 170 months to 88 months in the case of high VEGF-C expression (p = 0.041).
      Additionally, NRP2 and VEGF-C coexpression is a prognostic marker for OS in
      multivariate models (HR: 7.54; 95% CI: 1.57-36.23; p = 0.012). Stratification for
      muscle invasiveness (T1 vs. T2-T4) confirmed the prognostic role of NRP2 and
      NRP2/VEGF-C co-expression in patients with T2-T4 but also with high risk T1
      disease. In conclusion, immunohistochemistry for NRP2 and VEGF-C has been
      determined to predict therapy outcome in bladder cancer patients prior to TURBT
      and RCT.

PMID- 24862182
TI  - Synthesis of (3S,3'S)- and meso-stereoisomers of alloxanthin and determination of
      absolute configuration of alloxanthin isolated from aquatic animals.
AB  - In order to determine the absolute configuration of naturally occurring
      alloxanthin, a HPLC analytical method for three stereoisomers 1a-c was
      established by using a chiral column. Two authentic samples, (3S,3'S)- and meso
      stereoisomers 1b and 1c, were chemically synthesized according to the method
      previously developed for (3R,3'R)-alloxanthin (1a). Application of this method to
      various alloxanthin specimens of aquatic animals demonstrated that those isolated
      from shellfishes, tunicates, and crucian carp are identical with (3R,3'R)
      stereoisomer 1a, and unexpectedly those from lake shrimp, catfish, biwa goby, and
      biwa trout are mixtures of three stereoisomers of 1a-c. 

PMID- 24862184
TI  - Pressure ulcer education improves interrater reliability, identification, and
      classification skills by emergency nurses and physicians.
AB  - INTRODUCTION: Pressure ulcers (PUs) are a serious health complication that
      develop as a result of pressure alone or pressure in combination with shearing
      forces. Although PUs are typically associated with older adults and chronic
      illness, acutely injured trauma patients may have a particular risk for the
      development of PUs. To prevent PU development or detect PUs in an early stage,
      skin assessment and PU classification should start during the ED stay, before
      hospital admission. The aim of this study was to assess the PU identification and
      classification skills of emergency nurses and emergency physicians and to
      evaluate the short-term effect of an educational intervention. METHODS: Twenty
      validated photographs were used to test identification and classification skills
      in a one-group pretest/posttest design, before and after an educational
      intervention with 54 emergency nurses and physicians. In addition, we assessed
      the interrater reliability of PU identification and classification. RESULTS: PU
      identification and classification skills and the multirater kappa improved after
      the educational intervention. Accurate identification improved significantly from
      87.7% to 95.6% (P = .000), and classification skills improved significantly from
      68.5% to 79.8% (P = .000). The multirater kappa for identification of PU
      increased from 0.63 to 0.82, and the multirater kappa for classification of PUs
      rose from 0.43 to 0.58. The most frequently misclassified photographs were those
      that displayed category 1, 2, and 3 PUs, which were usually classified as more
      severe. DISCUSSION: This study investigated the effect of an educational
      intervention on the interrater reliability, PU identification, and PU
      classification skills of emergency nurses and physicians when tested immediately
      after the intervention. Study results show that interrater reliability, PU
      identification, and PU classification of photographs all improved, but
      identifying the presence of a PU in a photograph was less challenging than
      categorizing the same wound.

PMID- 24862183
TI  - Isolation and identification of antitrypanosomal and antimycobacterial active
      steroids from the sponge Haliclona simulans.
AB  - The marine sponge Haliclona simulans collected from the Irish Sea yielded two new
      steroids: 24-vinyl-cholest-9-ene-3beta,24-diol and 20-methyl-pregn-6-en-3beta
      ol,5a,8a-epidioxy, along with the widely distributed 24-methylenecholesterol. One
      of the steroids possesses an unusually short hydrocarbon side chain. The
      structures were elucidated using nuclear magnetic resonance spectroscopy and
      confirmed using electron impact- and high resolution electrospray-mass
      spectrometry. All three steroids possess antitrypanosomal and anti-mycobacterial
      activity. All the steroids were found to possess low cytotoxicity against Hs27
      which was above their detected antitrypanosomal potent concentrations. 

PMID- 24862185
TI  - Superdirective dielectric nanoantennas.
AB  - We introduce the novel concept of superdirective nanoantennas based on the
      excitation of higher-order magnetic multipole moments in subwavelength dielectric
      nanoparticles. Our superdirective nanoantenna is a small Si nanosphere containing
      a notch, and is excited by a dipole located within the notch. In addition to
      extraordinary directivity, this nanoantenna demonstrates efficient radiation
      steering at the nanoscale, resulting from the subwavelength sensitivity of the
      beam radiation direction to variation of the source position inside the notch. We
      compare our dielectric nanoantenna with a plasmonic nanoantenna of similar
      geometry, and reveal that the nanoantenna's high directivity in the regime of
      transmission is not associated with strong localization of near fields in the
      regime of reception. Likewise, the absence of hot spots inside the nanoantenna
      leads to low dissipation in the radiation regime, so that our dielectric
      nanoantenna has significantly smaller losses and high radiation efficiency of up
      to 70%. 

PMID- 24862186
TI  - Eastern equine encephalitis cases among horses in Brazil between 2005 and 2009.
AB  - Eastern equine encephalitis is a viral zoonosis that exhibits complex
      distribution and epidemiology, and greater importance should be given to this
      disease by the public-health authorities. In Brazil, although eastern equine
      encephalitis virus (EEEV) has been identified in vectors and antibodies are
      sometimes detected in horses and humans, there have been no records of equine
      encephalitis in horses caused by this virus during the last 24 years. This study
      describes eighteen cases of eastern equine encephalomyelitis that occurred in six
      Brazilian states between 2005 and 2009. Viral RNA was identified using semi
      nested RT-PCR to detect members of the genus Alphavirus, and by genetic
      sequencing. The gene encoding NSP1 was partially amplified, and after genetic
      sequencing, eighteen sequences were generated. All eighteen strains were
      classified as belonging to lineage III of American EEEV. These findings could be
      an indication of the importance of this virus in animal and human public health. 

PMID- 24862187
TI  - Caraparu virus induces damage and alterations in antioxidant defenses in the
      liver of BALB/c mice after subcutaneous infection.
AB  - Oxidative stress is a disturbance in the oxidant-antioxidant balance leading to
      potential cellular damage. Most cells can tolerate a mild degree of oxidative
      stress because they have a system that counteracts oxidation that includes
      antioxidant molecules such as glutathione (GSH) and superoxide dismutase (SOD).
      Disruption of the host antioxidant status has been recognized as an important
      contributor to the pathogenesis of many viruses. Caraparu virus (CARV) is a
      member of group C of the Bunyaviridae family of viruses. In South American
      countries, group C bunyaviruses are among the common agents of human febrile
      illness and have caused multiple notable outbreaks of human disease in recent
      decades; nevertheless, little is known about the pathogenic characteristics of
      these viruses. The purpose of this study was to examine the hepatic pathogenesis
      of CARV in mice and the involvement of oxidative stress and antioxidant defenses
      on this pathology. Following subcutaneous infection of BALB/c mice, CARV was
      detected in the liver, and histopathology revealed acute hepatitis. Increased
      serum levels of aspartate and alanine aminotransferases (AST/ALT) and greater
      hepatic expression of the proinflammatory cytokine tumor necrosis factor-alpha
      (TNF-alpha) were found in infected animals. CARV infection did not alter the
      biomarkers of oxidative stress but caused an increase in GSH content and altered
      the expression and activity of SOD. This is the first report of an alteration of
      oxidative homeostasis upon CARV infection, which may, in part, explain the
      hepatic pathogenesis of this virus, as well as the pathogenesis of other
      Bunyaviridae members.

PMID- 24862188
TI  - The zoonotic potential of avian influenza viruses isolated from wild waterfowl in
      Zambia.
AB  - Whilst remarkable progress in elucidating the mechanisms governing interspecies
      transmission and pathogenicity of highly pathogenic avian influenza viruses
      (AIVs) has been made, similar studies focusing on low-pathogenic AIVs isolated
      from the wild waterfowl reservoir are limited. We previously reported that two
      AIV strains (subtypes H6N2 and H3N8) isolated from wild waterfowl in Zambia
      harbored some amino acid residues preferentially associated with human influenza
      virus proteins (so-called human signatures) and replicated better in the lungs of
      infected mice and caused more morbidity than a strain lacking such residues. To
      further substantiate these observations, we infected chickens and mice
      intranasally with AIV strains of various subtypes (H3N6, H3N8, H4N6, H6N2, H9N1
      and H11N9) isolated from wild waterfowl in Zambia. Although some strains induced
      seroconversion, all of the tested strains replicated poorly and were
      nonpathogenic for chickens. In contrast, most of the strains having human
      signatures replicated well in the lungs of mice, and one of these strains caused
      severe illness in mice and induced lung injury that was characterized by a severe
      accumulation of polymorphonuclear leukocytes. These results suggest that some
      strains tested in this study may have the potential to infect mammalian hosts
      directly without adaptation, which might possibly be associated with the
      possession of human signature residues. Close monitoring and evaluation of host
      associated signatures may help to elucidate the prevalence and emergence of AIVs
      with potential for causing zoonotic infections. 

PMID- 24862189
TI  - The synergistic effect of humanized monoclonal antibodies targeting insulin-like
      growth factor 1 receptor (IGF-1R) and chemotherapy.
AB  - IGF-1R, an important member of the IGF signaling system, is a plasma-membrane
      bound receptor composed of two alpha-subunits and two beta-subunits. IGF-1R has
      been revealed to play a pivotal role in cancer cell proliferation,
      differentiation, apoptosis and phenotype transformation, resulting uncontrolled
      tumor-cell growth. During the last decades, IGF-1R monoclonal antibody combined
      with chemotherapeutic agents as a novel cancer treatment approach has shown
      synergistic effect in cancer treatment in some preclinical and clinical trials.
      Prolonged progression-free survival rate, objective response rate and stable
      disease were shown in some sorts of cancer patients compared to those implemented
      traditional standard chemotherapy. However, not all related clinical trials
      demonstrated expected promising outcomes. Most treatment-related adverse events
      in those studies are mild and manageable. The most frequently happened side
      effect is hyperglycemia in majorities of combined cancer therapy studies. Herein,
      we summarized the recent online and published literatures concerning the safety,
      tolerability, anti-tumor activity and adverse events of this novel strategy.
      Besides, this work attempts to provide convincible evidence to warrant further
      investigation to identify prognostic biomarkers on neoplasm. 

PMID- 24862190
TI  - Mechanics of fragmentation of crocodile skin and other thin films.
AB  - Fragmentation of thin layers of materials is mediated by a network of cracks on
      its surface. It is commonly seen in dehydrated paintings or asphalt pavements and
      even in graphene or other two-dimensional materials, but is also observed in the
      characteristic polygonal pattern on a crocodile's head. Here, we build a simple
      mechanical model of a thin film and investigate the generation and development of
      fragmentation patterns as the material is exposed to various modes of
      deformation. We find that the characteristic size of fragmentation, defined by
      the mean diameter of polygons, is strictly governed by mechanical properties of
      the film material. Our result demonstrates that skin fragmentation on the head of
      crocodiles is dominated by that it features a small ratio between the fracture
      energy and Young's modulus, and the patterns agree well with experimental
      observations. Understanding this mechanics-driven process could be applied to
      improve the lifetime and reliability of thin film coatings by mimicking crocodile
      skin. 

PMID- 24862191
TI  - Microscale acoustic disruption of mammalian cells for intracellular product
      release.
AB  - High-throughput microscale models for cell culture are critical for
      biopharmaceutical process development and drug discovery compound screening.
      While analytical methods are readily available for quantifying cell number and
      secreted product concentration, the recovery and measurement of intracellular
      products are significantly affected by the method of cell disruption. For
      example, the detergents often used in product extraction are incompatible with
      lipid-enveloped viruses. To provide an alternative to detergent-mediated
      disruption of mammalian cells, we have developed an effective yet gentle
      mechanical method compatible with 96-well plates using adaptive focused acoustics
      technology. This method was adapted for the release of Varicella-Zoster virus
      from MRC-5 cells and then applied to investigate infectious virus yield as a
      function of the cell density at infection. This microscale, high-throughput
      mechanical cell disruption method may be applicable to a variety of mammalian
      cell culture systems and intracellular products, thus expanding the scope of high
      throughput screening. 

PMID- 24862192
TI  - Analysis of multiple transcriptomes of the African oil palm (Elaeis guineensis)
      to identify reference genes for RT-qPCR.
AB  - The African oil palm (Elaeis guineensis), which is grown in tropical and
      subtropical regions, is a highly productive oil-bearing crop. For gene expression
      based analyses such as reverse transcription-quantitative real time PCR (RT
      qPCR), reference genes are essential to provide a baseline with which to quantify
      relative gene expression. Normalization using reliable reference genes is
      critical in correctly interpreting expression data from RT-qPCR. In order to
      identify suitable reference genes in African oil palm, 17 transcriptomes of
      different tissues obtained from NCBI were systematically assessed for gene
      expression variation. In total, 53 putative candidate reference genes with
      coefficient of variation values <3.0 were identified: 18 in reproductive tissue
      and 35 in vegetative tissue. Analysis for enriched functions showed that
      approximately 90% of identified genes were clustered in cell component gene
      functions, and 12 out of 53 genes were traditional housekeeping genes. We
      selected and validated 16 reference genes chosen from leaf tissue transcriptomes
      by using RT-qPCR in sets of cold, drought and high salinity treated samples, and
      ranked expression stability using statistical algorithms geNorm, Normfinder and
      Bestkeeper. Genes encoding actin, adenine phosphoribosyltransferase and
      eukaryotic initiation factor 4A genes were the most stable genes over the cold,
      drought and high salinity stresses. Identification of stably expressed genes as
      reference gene candidates from multiple transcriptome datasets was found to be
      reliable and efficient, and some traditional housekeeping genes were more stably
      expressed than others. We provide a useful molecular genetic resource for future
      gene expression studies in African oil palm, facilitating molecular genetics
      approaches for crop improvement in this species. 

PMID- 24862193
TI  - Shark Attack: high affinity binding proteins derived from shark vNAR domains by
      stepwise in vitro affinity maturation.
AB  - A novel method for stepwise in vitro affinity maturation of antigen-specific
      shark vNAR domains is described that exclusively relies on semi-synthetic
      repertoires derived from non-immunized sharks. Target-specific molecules were
      selected from a CDR3-randomized bamboo shark (Chiloscyllium plagiosum) vNAR
      library using yeast surface display as platform technology. Various antigen
      binding vNAR domains were easily isolated by screening against several
      therapeutically relevant antigens, including the epithelial cell adhesion
      molecule (EpCAM), the Ephrin type-A receptor 2 (EphA2), and the human serine
      protease HTRA1. Affinity maturation was demonstrated for EpCAM and HTRA1 by
      diversifying CDR1 of target-enriched populations which allowed for the rapid
      selection of nanomolar binders. EpCAM-specific vNAR molecules were produced as
      soluble proteins and more extensively characterized via thermal shift assays and
      biolayer interferometry. Essentially, we demonstrate that high-affinity binders
      can be generated in vitro without largely compromising the desirable high
      thermostability of the vNAR scaffold. 

PMID- 24862195
TI  - Dual-mode cultivation of Chlorella protothecoides applying inter-reactors gas
      transfer improves microalgae biodiesel production.
AB  - Chlorella protothecoides, a lipid-producing microalga, was grown
      heterotrophically and autotrophically in separate reactors, the off-gases exiting
      the former being used to aerate the latter. Autotrophic biomass productivity with
      the two-reactor association, 0.0249gL(-1)h(-1), was 2.2-fold the value obtained
      in a control autotrophic culture, aerated with ambient air. Fatty acid
      productivity was 1.7-fold the control value. C. protothecoides heterotrophic
      biomass productivity was 0.229gL(-1)h(-1). This biomass' fatty acid content was
      34.5% (w/w) with a profile suitable for biodiesel production, according to
      European Standards. The carbon dioxide fixed by the autotrophic biomass was
      45mgCO2L(-1)h(-1) in the symbiotic arrangement, 2.1 times the control reactor
      value. The avoided CO2 atmospheric emission represented 30% of the CO2 produced
      in the heterotrophic stage, while the released O2 represented 49% of the oxygen
      demand in that stage. Thus, an increased efficiency in the glucose carbon source
      use and a higher environmental sustainability were achieved in microalgal
      biodiesel production using the proposed assembly. 

PMID- 24862194
TI  - Evaluation of human embryonic stem cells and their differentiated fibroblastic
      progenies as cellular models for in vitro genotoxicity screening.
AB  - This study evaluated human embryonic stem cells (hESC) and their differentiated
      fibroblastic progenies as cellular models for genotoxicity screening. The DNA
      damage response of hESCs and their differentiated fibroblastic progenies were
      compared to a fibroblastic cell line (HEPM, CRL1486) and primary cultures of
      peripheral blood lymphocytes (PBL), upon exposure to Mitomycin C, gamma
      irradiation and H2O2. It was demonstrated that hESC-derived fibroblastic
      progenies (H1F) displayed significantly higher chromosomal aberrations,
      micronuclei formation and double strand break (DSB) formation, as compared to
      undifferentiated hESC upon exposure to genotoxic stress. Nevertheless, H1F cell
      types displayed comparable sensitivities to genotoxic challenge as HEPM and PBL,
      both of which are representative of somatic cell types commonly used for
      genotoxicity screening. Subsequently, transcriptomic and pathways analysis
      identified differential expression of critical genes involved in cell death and
      DNA damage response upon exposure to gamma irradiation. The results thus
      demonstrate that hESC-derived fibroblastic progenies are as sensitive as commonly
      used somatic cell types for genotoxicity screening. Moreover, hESCs have
      additional advantages, such as their genetic normality compared to immortalized
      cell lines, as well as their amenability to scale-up for producing large,
      standardized quantities of cells for genotoxicity screening on an industrial
      scale, something which can never be achieved with primary cell cultures. 

PMID- 24862196
TI  - Rhodamine B doped silica encapsulation matrices for the protection of
      photosynthetic organisms.
AB  - An advanced encapsulation matrix that efficiently protects microalgae from
      harmful UV light without causing toxicity to the entrapped culture is developed
      based on the electrostatic adsorption of the dye Rhodamine B on silica preformed
      particles during sol-gel synthesis. The three microalgae (Chlorella vulgaris,
      Pseudokirchneriella subcapitata and Chlamydomonas reinhardtii) were previously
      immobilized in alginate following the Two-step procedure. Once entrapped in the
      silica gel, Rhodamine B act as an inner cut-off filter, protecting the
      encapsulated organisms from UV radiation. This matrix allows the sterilization of
      encapsulation devices without affecting the viability of the entrapped microalgae
      cells. The condensation of Si(IV) in the presence of silica particles with
      adsorbed dye generates silica matrices with good mechanical stability.
      Furthermore; no appreciable differences in microstructure, as assessed by SAXS
      (Small Angle X-ray Scattering), are caused by the addition of the dye. 

PMID- 24862197
TI  - Identification and characterization of peptide fragments for the direct and site
      specific immobilization of functional proteins onto the surface of silicon
      nitride.
AB  - In this study, we successfully identified peptide fragments that have a strong
      affinity toward the surface of a silicon nitride (SiN) substrate. An E. coli
      soluble protein, which was preferentially adsorbed onto the surface of a SiN
      substrate was isolated by 2D electrophoresis, and it was identified as
      "elongation factor Tu (ELN)" via the peptide MS fingerprinting method. A
      recombinant ELN that was originally cloned and produced, also maintained its
      adsorptive ability to a SiN substrate, by comparison with BSA that was used as a
      control protein. The peptide fragments derived from the recombinant ELN were
      prepared via 3 types of proteases with different recognition properties (trypsin,
      chymotrypsin and V8 protease). The peptide mixture was applied to the surface of
      a SiN substrate, and then, the SiN-binding peptide candidates were isolated and
      identified. The amino acid sequences of the peptide candidates were genetically
      fused with the C-terminal region of glutathione S-transferase as a model protein,
      and the adsorption properties of mutant-type GSTs on the surface of a SiN
      substrate were directly monitored using a reflectometric interference
      spectroscopy (RIfS) sensor system. Consequently, among the 8 candidates
      identified, the genetic fusion of TP14, V821 and CT22 peptides resulted in a
      significant enhancement of GST adsorption to the surface of the SiN substrate,
      while the adsorption of a wild-type GST was hardly detectable by RIfS sensor.
      These peptide fragments were located at the C-terminal region in the aminoacid
      sequence of recombinant ELN. Interestingly, the sequence with the shortest and
      strongest SiN-binding peptide, TP14 (GYRPQFYFR), was also found in that of V821
      (GGRHTPFFKGYRPQFYFRTTDVTGTIE). The TP14 peptide might be the smallest unit of SiN
      binding peptide, and a clarification of the amino acid contribution in TP14
      peptide will be the next subject. Three-fold higher enzymatic activities were
      detected from the SiN substrate immobilized with GST-TP14 and GST-V821 due to a
      higher density of enzyme through the SiN-binding peptides. Thus, the SiN-binding
      peptides identified in this study will be considerably useful for the
      immobilization of target proteins with high density and biological activity onto
      the surfaces of SiN substrates, and these will be applicable to the task of
      coating proteins onto the surface of SiN-based RIfS sensors and semiconductors. 

PMID- 24862198
TI  - Electrospun ultrafine fibrous wheat glutenin scaffolds with three-dimensionally
      random organization and water stability for soft tissue engineering.
AB  - Wheat glutenin, the highly crosslinked protein from wheat, was electrospun into
      scaffolds with ultrafine fibers oriented randomly and evenly in three dimensions
      to simulate native extracellular matrices of soft tissues. The scaffolds were
      intrinsically water-stable without using any external crosslinkers and could
      support proliferation and differentiation of adipose-derived mesenchymal stem
      cells for soft tissue engineering. Regeneration of soft tissue favored water
      stable fibrous protein scaffolds with three-dimensional arrangement and large
      volumes, which could be difficult to obtain via electrospinning. Wheat glutenin
      is an intrinsically water-stable protein due to the 2% cysteine in its amino acid
      composition. In this research, the disulfide crosslinks in wheat glutenin were
      cleaved while the backbones were preserved. The treated wheat glutenin was
      dissolved in aqueous solvent with an anionic surfactant and then electrospun into
      bulky scaffolds composed of ultrafine fibers oriented randomly in three
      dimensions. The scaffolds could maintain their fibrous structures after incubated
      in PBS for up to 35 days. In vitro study indicated that the three-dimensional
      wheat glutenin scaffolds well supported uniform distribution and adipogenic
      differentiation of adipose derived mesenchymal stem cells. 

PMID- 24862199
TI  - Depth profiles of methane oxidation potentials and methanotrophic community in a
      lab-scale biocover.
AB  - The depth profiles of the CH4 oxidation potentials and the methanotrophic
      community were characterized in a lab-scale soil mixture biocover. The soil
      mixture samples were collected from the top (0-10cm), middle (10-40cm), and
      bottom (40-50cm) layers of the biocover where most of methane was oxidized at the
      top layer due to consumption of O2. Batch tests using serum bottles showed that
      the middle and bottom samples displayed CH4 oxidation activity under aerobic
      conditions, and their CH4 oxidation rates were 85 and 71% of the rate of top
      sample (8.40MUmolgdry sample(-1)h(-1)), respectively. The numbers of
      methanotrophs in the middle and bottom were not significantly different from
      those in the top sample. There was no statistical difference in the community
      stability indices (diversity and evenness) among the methanotrophic communities
      of the three layer samples, even though the community structures were
      distinguished from each other. Based on microarray analysis, type I and type II
      methanotrophs were equally present in the top sample, while type I was more
      dominant than type II in the middle and bottom samples. We suggested that the
      qualitative difference in the community structures was probably caused by the
      difference in the depth profiles of the CH4 and O2 concentrations. The results
      for the CH4 oxidation potential, methanotrophic biomass, and community stability
      indices in the middle and bottom layer samples indicated that the deeper layer in
      the methanotrophic biocover serves as a bioresource reservoir for sustainable CH4
      mitigation. 

PMID- 24862200
TI  - In vitro molecular evolution of AL NEIBMs improved immunoglobulin (Ig) binding
      and antibody detection.
AB  - AL (SpA A domain-PpL B3 domain), LD5 (PpL B3 domain-SpA D domain-PpL B3 domain
      SpA D domain-PpL B3 domain, L-D-L-D-L) and LD3 (PpL B3 domain-SpA D domain-PpL B3
      domain, L-D-L) are novel evolved Ig binding molecules (NEIBMs) derived from the
      in vitro molecular evolution of combinatorial phage libraries displaying randomly
      rearranged Ig-binding domains of protein A and protein L. These molecules all
      showed novel Ig-binding properties of double-site binding to the VH3 and Vkappa
      regions of human Ig Fab and high affinity for human IgM, which enhanced IgM
      detection in the anti-HCV ELISA assay. In this double-site binding, the A domain
      binds to the VH3 chain with low affinity. Whether the appropriate mutations in
      the A domain could improve this binding remains unknown. In this study, four
      combinatorial phage libraries displaying AL mutants with random mutations at
      different amino acid positions in the A domain were constructed. Seven AL mutant
      phages with significantly improved Ig binding activity were obtained from the
      phage library displaying AL mutants randomly mutated at positions 27 and 34
      through human IgM-directed in vitro evolution. Two of the seven prokaryotically
      expressed AL mutants, AL (VV) and AL (KA), exhibited IgM and IgG binding
      activities equivalent to those of wild-type AL, whereas other mutants showed
      attenuated binding. However, after labeling with HRP, AL (VV) and AL (KA) showed
      improved IgM and IgG binding activity, which significantly improved the detection
      in the anti-HCV assay. Thus, the present study demonstrates that the binding
      properties of AL were successfully improved through phage-based molecular
      evolution, which could substantially contribute to the use of AL in antibody
      detection, and provides an example of successful protein engineering through in
      vitro molecular evolution. 

PMID- 24862201
TI  - Investigating the genetic polymorphism of sheep milk proteins: a useful tool for
      dairy production.
AB  - Sheep is the second most important dairy species after cow worldwide, and
      especially in the Mediterranean and Middle East regions. In some countries, the
      difficult environmental conditions require a peculiar adaptation and, in these
      contexts, sheep are able to provide higher quality protein than cattle. In the
      least-developed countries, the amount of dairy sheep and ovine milk production is
      progressively increasing. In order to improve dairy productions, in particular
      those with local connotations, it is necessary to obtain in-depth information
      regarding milk quality and rheological properties. The genetic polymorphisms of
      milk proteins are often associated with quantitative and qualitative parameters
      in milk and are potential candidate markers that should be included in breeding
      strategies similar to those already available for cattle. Due to the current and
      growing interest in this topic and considering the large amount of new
      information, the aim of this study was to review the literature on sheep milk
      protein polymorphisms with a particular emphasis on recent findings in order to
      give scientists useful support. Moreover, the effects of different protein
      variants on milk yield and composition are discussed.

PMID- 24862202
TI  - Enhancement of the photovoltaic performance of CH3NH3PbI3 perovskite solar cells
      through a dichlorobenzene-functionalized hole-transporting material.
AB  - A dichlorobenzene-functionalized hole-transporting material (HTM) is developed
      for a CH3NH3PbI3-based perovskite solar cell. Notwithstanding the similarity of
      the frontier molecular orbital energy levels, optical properties, and hole
      mobility between the functionalized HTM [a polymer composed of 2'-butyloctyl-4,6
      dibromo-3-fluorothieno[3,4-b]thiophene-2-carboxylate (TT-BO), 3',4'
      dichlorobenzyl-4,6-dibromo-3-fluorothieno[3,4-b]thiophene-2-carboxylate (TT-DCB),
      and 2,6-bis(trimethyltin)-4,8-bis(2-ethylhexyloxy)benzo[1,2-b:4,5-b']dithiophene
      (BDT-EH), denoted PTB-DCB21] and the nonfunctionalized polymer [a polymer
      composed of thieno[3,4-b]thiophene (TT) and benzo[1,2-b:4,5-b']dithiophene (BDT),
      denoted PTB-BO], a higher power conversion efficiency for PTB-DCB21 (8.7%) than
      that for PTB-BO (7.4%) is achieved because of a higher photocurrent and voltage.
      The high efficiency is even obtained without including additives, such as lithium
      bis(trifluoromethanesulfonyl)imide and/or 4-tert-butylpyridine, that are commonly
      used to improve the conductivity of the HTM. Transient photocurrent-voltage
      studies show that the PTB-DCB21-based device exhibits faster electron transport
      and slower charge recombination; this might be related to better interfacial
      contact through intermolecular chemical interactions between the perovskite and
      the 3,4-dichlorobenzyl group in PTB-DCB21.

PMID- 24862203
TI  - Lambert-Eaton syndrome antibodies target multiple subunits of voltage-gated Ca2+
      channels.
AB  - INTRODUCTION: Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune
      presynaptic neuromuscular disorder. Autoantibodies against subunits of voltage
      gated calcium channels (VGCCs) associated with acetylcholine release are thought
      to cause LEMS. METHODS: HEK293 cells expressing specific individual recombinant
      subunits of alpha(1A), alpha(1B), alpha(1C), and alpha(1E); beta(3); and
      alpha(2)delta of human neuronal VGCCs were exposed to antibodies from 3 LEMS
      patients, 1 patient with small-cell lung carcinoma, and 1 with myasthenia gravis.
      RESULTS: All LEMS patient antibodies bound to cells containing any of the
      alpha(1) or beta(3) subunits alone or combined with alpha(2)delta subunits, but
      not alpha(2)delta alone. Autoantibodies from the patient with small-cell lung
      carcinoma but not the myasthenia gravis patient targeted the same VGCC subunits.
      CONCLUSIONS: Autoantibodies from LEMS patients bind directly to multiple VGCC
      alpha(1) subunits as well as the beta(3) subunit. Thus, multiple components of
      the presynaptic VGCC complex are prospective targets for antibodies in LEMS.

PMID- 24862205
TI  - Peritonitis caused by Blastomyces dermatitidis in a kidney transplant recipient:
      case report and literature review.
AB  - Blastomyces dermatitidis is a dimorphic fungus endemic to the midwestern, south
      central, and southeastern United States known to cause disseminated infection in
      immunocompromised individuals. We report a case of B. dermatitidis peritonitis in
      a renal allograft recipient with new-onset ascites and cytomegalovirus
      encephalitis. Peritoneal blastomycosis is a rare clinical entity and, to our
      knowledge, this patient represents the first known case of peritoneal
      blastomycosis in a solid organ transplant recipient. We review the clinical
      characteristics of B. dermatitidis peritonitis as well as the literature on
      fungal peritonitis with emphasis on dimorphic fungal pathogens. Clinical features
      suggestive of fungal peritonitis include new-onset ascites, abdominal pain, and
      fevers, especially with antecedent or concomitant pneumonia. A high index of
      clinical suspicion, along with the use of culture and non-culture diagnostics, is
      needed for early diagnosis and prompt initiation of therapy. 

PMID- 24862204
TI  - Antiepileptic activity of preferential inhibitors of persistent sodium current.
AB  - OBJECTIVE: Evidence from basic neurophysiology and molecular genetics has
      implicated persistent sodium current conducted by voltage-gated sodium (NaV )
      channels as a contributor to the pathogenesis of epilepsy. Many antiepileptic
      drugs target NaV channels and modulate neuronal excitability, mainly by a use
      dependent block of transient sodium current, although suppression of persistent
      current may also contribute to the efficacy of these drugs. We hypothesized that
      a drug or compound capable of preferential inhibition of persistent sodium
      current would have antiepileptic activity. METHODS: We examined the antiepileptic
      activity of two selective persistent sodium current blockers ranolazine, a U.S.
      Food and Drug Administration (FDA)-approved drug for treatment of angina
      pectoris, and GS967, a novel compound with more potent effects on persistent
      current, in the epileptic Scn2a(Q54) mouse model. We also examined the effect of
      GS967 in the maximal electroshock model and evaluated effects of the compound on
      neuronal excitability, propensity for hilar neuron loss, development of mossy
      fiber sprouting, and survival of Scn2a(Q54) mice. RESULTS: We found that
      ranolazine was capable of reducing seizure frequency by approximately 50% in
      Scn2a(Q54) mice. The more potent persistent current blocker GS967 reduced seizure
      frequency by >90% in Scn2a(Q54) mice and protected against induced seizures in
      the maximal electroshock model. GS967 greatly attenuated abnormal spontaneous
      action potential firing in pyramidal neurons acutely isolated from Scn2a(Q54)
      mice. In addition to seizure suppression in vivo, GS967 treatment greatly
      improved the survival of Scn2a(Q54) mice, prevented hilar neuron loss, and
      suppressed the development of hippocampal mossy fiber sprouting. SIGNIFICANCE:
      Our findings indicate that the selective persistent sodium current blocker GS967
      has potent antiepileptic activity and that this compound could inform development
      of new agents.

PMID- 24862208
TI  - The tale of 2 trials: disentangling contradictory evidence on hypertonic saline
      for acute bronchiolitis.

PMID- 24862207
TI  - RNA-directed DNA methylation requires stepwise binding of silencing factors to
      long non-coding RNA.
AB  - Ribonucleic acid-mediated transcriptional gene silencing (known as RNA-directed
      DNA methylation, or RdDM, in Arabidopsis thaliana) is important for influencing
      gene expression and the inhibition of transposons by the deposition of repressive
      chromatin marks such as histone modifications and DNA methylation. A key event in
      de novo methylation of DNA by RdDM is the production of long non-coding RNA
      (lncRNA) by RNA polymerase V (Pol V). Little is known about the events that
      connect Pol V transcription to the establishment of repressive chromatin
      modifications. Using RNA immunoprecipitation, we elucidated the order of events
      downstream of lncRNA production and discovered interdependency between lncRNA
      associated proteins. We found that the effector protein ARGONAUTE4 (AGO4) binds
      lncRNA independent of the RNA-binding protein INVOLVED IN DE NOVO2 (IDN2). In
      contrast, IDN2 binds lncRNA in an AGO4-dependent manner. We further found that
      the de novo DNA methyltransferase DOMAINS REARRANGED METHYLTRANSFERASE2 (DRM2)
      also associates with lncRNA produced by Pol V and that this event depends on AGO4
      and IDN2. We propose a model where the silencing proteins AGO4, IDN2 and DRM2
      bind to lncRNA in a stepwise manner, resulting in DNA methylation of RdDM target
      loci.

PMID- 24862209
TI  - Visualization of phagosomal hydrogen peroxide production by a novel fluorescent
      probe that is localized via SNAP-tag labeling.
AB  - Hydrogen peroxide (H2O2), a member of reactive oxygen species (ROS), plays
      diverse physiological roles including host defense and cellular signal
      transduction. During ingestion of invading microorganisms, professional
      phagocytes such as macrophages release H2O2 specifically into the phagosome to
      direct toxic ROS toward engulfed microbes. Although H2O2 is considered to exert
      discrete effects in living systems depending on location of its production,
      accumulation, and consumption, there have been limitations of techniques for
      probing this oxygen metabolite with high molecular specificity at the subcellular
      resolution. Here we describe the development of an O(6)-benzylguanine derivative
      of 5-(4-nitrobenzoyl)carbonylfluorescein (NBzF-BG), a novel H2O2-specific
      fluorescent probe; NBzF-BG is covalently and selectively conjugated with the SNAP
      tag protein, leading to formation of the fluorophore-protein conjugate (SNAP
      NBzF). SNAP-NBzF rapidly reacts with H2O2 and thereby shows a 9-fold enhancement
      in fluorescence. When SNAP-tag is expressed in HEK293T cells and RAW264.7
      macrophages as a protein C-terminally fused to the transmembrane domain of
      platelet-derived growth factor receptor (PDGFR), the tag is presented on the
      outside of the plasma membrane; conjugation of NBzF-BG with the cell surface SNAP
      tag enables detection of H2O2 added exogenously. We also demonstrate molecular
      imaging of H2O2 that is endogenously produced in phagosomes of macrophages
      ingesting IgG-coated latex beads. Thus, NBzF-BG, combined with the SNAP-tag
      technology, should be useful as a tool to measure local production of H2O2 in
      living cells. 

PMID- 24862210
TI  - Current management and future perspectives of metastatic renal cell carcinoma.
AB  - Over the last number of years, the treatment of metastatic renal cell cancer has
      evolved tremendously with the advent of targeted therapy. Previously,
      immunotherapies, such as interferon alpha and interleukin-2, were the only
      treatment options available for this chemoresistant malignancy. Currently, seven
      additional agents, including sunitinib, sorafenib, axitinib, pazopanib,
      bevacizumab, everolimus and temsirolimus, have been approved for use in
      metastatic renal cell cancer, with several more in development. The efficacy of
      these agents depends primarily on inhibition of the vascular endothelial growth
      factor and mammalian target of rapamycin pathways, and have drastically improved
      the outcomes of patients diagnosed with metastatic renal cell cancer. This
      article reviews the major treatment advances that have occurred for metastatic
      renal cell cancer with the advent of targeted treatments, summarizes the evidence
      to support their use and addresses clinical issues that have arisen with them. To
      help guide clinicians in their decision-making with these emerging therapeutic
      choices, the evidence for sequencing and combining these agents, and the need for
      biomarkers will be addressed. The role of surgical management options, such as
      cytoreductive nephrectomy and metastectomy, in the era of targeted treatment is
      also reviewed. Several novel treatments are also on the horizon, which might
      serve as future avenues for treatment advancement in metastatic renal cell
      cancer. 

PMID- 24862211
TI  - Intra-population variation in anemia status and its relationship to economic
      status and self-perceived health in the Mexican Family Life Survey: implications
      for bioarchaeology.
AB  - Recently scholars have advocated for the use of a critical biocultural approach
      in bioarchaeology, where osteological and dental markers of stress are used to
      understand the broader biosocial context of past populations. However, the
      ability to accomplish this task rests on the assumption that ultimate-level
      environmental stressors and well-being in the past can be reconstructed from the
      prevalence of pathologies in skeletal collections. Here we test this assumption
      using anemia prevalence in the Mexican Family Life Survey. Specifically we test
      three hypotheses: (1) that individuals sharing the same household are more likely
      to share anemia status; (2) anemia status is a predictor of economic status (a
      common proxy for broader environmental context); and (3) anemia status is related
      to self-rated health. Results demonstrate that: anemia status was not commonly
      shared between household members; there was a significant overlap in economic
      status between anemic and nonanemic individuals (i.e., anemia poorly predicted
      economic status) and; while anemia status was associated with self-perceived
      health, the majority of those who reported poor health were nonanemic while a
      significant number of those who reported very good health were anemic. We argue
      that these findings are likely related to variation in individual frailty, which
      is shaped by biological and cultural risk factors. Therefore, we advocate for
      greater incorporation of individual frailty into bioarchaeological
      investigations, and, in effort to overcome some of the difficulties associated
      with this task, increased use of data from living populations and greater
      collaboration between bioarchaeologists and human biologists.

PMID- 24862206
TI  - Mitochondrial mechanisms in cerebral vascular control: shared signaling pathways
      with preconditioning.
AB  - Mitochondrial-initiated events protect the neurovascular unit against lethal
      stress via a process called preconditioning, which independently promotes changes
      in cerebrovascular tone through shared signaling pathways. Activation of
      adenosine triphosphate (ATP)-dependent potassium channels on the inner
      mitochondrial membrane (mitoKATP channels) is a specific and dependable way to
      induce protection of neurons, astroglia, and cerebral vascular endothelium.
      Through the opening of mitoKATP channels, mitochondrial depolarization leads to
      activation of protein kinases and transient increases in cytosolic calcium
      (Ca(2+)) levels that activate terminal mechanisms that protect the neurovascular
      unit against lethal stress. The release of reactive oxygen species from
      mitochondria has similar protective effects. Signaling elements of the
      preconditioning pathways also are involved in the regulation of vascular tone.
      Activation of mitoKATP channels in cerebral arteries causes vasodilation, with
      cell-specific contributions from the endothelium, vascular smooth muscles, and
      nerves. Preexisting chronic conditions, such as insulin resistance and/or
      diabetes, prevent preconditioning and impair relaxation to mitochondrial-centered
      responses in cerebral arteries. Surprisingly, mitochondrial activation after
      anoxic or ischemic stress appears to protect cerebral vascular endothelium and
      promotes the restoration of blood flow; therefore, mitochondria may represent an
      important, but underutilized target in attenuating vascular dysfunction and brain
      injury in stroke patients.

PMID- 24862212
TI  - The human cathelicidin LL-37 host defense peptide upregulates tight junction
      related proteins and increases human epidermal keratinocyte barrier function.
AB  - Both psoriasis and atopic dermatitis (AD) are not only associated with an
      impaired stratum corneum barrier, but also with abnormal expression of the tight
      junction (TJ) proteins. Because host defense peptides, including LL-37, are
      overexpressed in lesional psoriatic skin but are downregulated in lesional AD
      skin, we hypothesized that LL-37 might regulate the TJ function in keratinocytes.
      We demonstrated that LL-37 selectively increased the expression of several
      claudins and occludin, and enhanced their membrane distribution. Furthermore, LL
      37 elevated the transepithelial electrical resistance while reducing the
      paracellular permeability of keratinocyte layers, and this activity was weakened
      by the claudin inhibitor ochratoxin A. A characterization of the molecular
      mechanism underlying the regulation of the TJ barrier by LL-37 revealed that LL
      37 induced the activation of the Rac1, atypical PKC, glycogen synthase kinase-3
      and PI3K pathways, and the specific inhibition of these pathways reversed the LL
      37-mediated regulation of TJ function. In addition, LL-37 enhanced the expression
      of differentiation markers under the control of ochratoxin A, suggesting an
      association between LL-37-induced TJ function and keratinocyte differentiation.
      These data provide novel evidence that, in addition to its antimicrobial and
      other immunoregulatory functions, LL-37 contributes to cutaneous immunity by
      strengthening the skin's barrier function.

PMID- 24862213
TI  - Relationship between body mass index and fracture risk is mediated by bone
      mineral density.
AB  - The relationship between body mass index (BMI) and fracture risk is
      controversial. We sought to investigate the effect of collinearity between BMI
      and bone mineral density (BMD) on fracture risk, and to estimate the direct and
      indirect effect of BMI on fracture with BMD being the mediator. The study
      involved 2199 women and 1351 men aged 60 years or older. BMI was derived from
      baseline weight and height. Femoral neck BMD was measured by dual-energy X-ray
      absorptiometry (DXA; GE-LUNAR, Madison, WI, USA). The incidence of fragility
      fracture was ascertained by X-ray reports from 1991 through 2012. Causal
      mediation analysis was used to assess the mediated effect of BMD on the BMI
      fracture relationship. Overall, 774 women (35% of total women) and 258 men (19%)
      had sustained a fracture. Approximately 21% of women and 20% of men were
      considered obese (BMI >= 30). In univariate analysis, greater BMI was associated
      with reduced fracture risk in women (hazard ratio [HR] 0.92; 95% confidence
      interval [CI], 0.85 to 0.99) and in men (HR 0.77; 95% CI, 0.67 to 0.88). After
      adjusting for femoral neck BMD, higher BMI was associated with greater risk of
      fracture in women (HR 1.21; 95% CI, 1.11 to 1.31) but not in men (HR 0.96; 95%
      CI, 0.83 to 1.11). Collinearity had minimal impact on the BMD-adjusted results
      (variance inflation factor [VIF] = 1.2 for men and women). However, in mediation
      analysis, it was found that the majority of BMI effect on fracture risk was
      mediated by femoral neck BMD. The overall mediated effect estimates were -0.048
      (95% CI, -0.059 to -0.036; p < 0.001) in women and -0.030 (95% CI, -0.042 to 
      0.018; p < 0.001) in men. These analyses suggest that there is no significant
      direct effect of BMI on fracture, and that the observed association between BMI
      and fracture risk is mediated by femoral neck BMD in both men and women.

PMID- 24862214
TI  - National spatial and temporal patterns of notified dengue cases, Colombia 2007
      2010.
AB  - OBJECTIVES: To explore the variation in the spatial distribution of notified
      dengue cases in Colombia from January 2007 to December 2010 and examine
      associations between the disease and selected environmental risk factors.
      METHODS: Data on the number of notified dengue cases in Colombia were obtained
      from the National Institute of Health (Instituto Nacional de Salud - INS) for the
      period 1 January 2007 through 31 December 2010. Data on environmental factors
      were collected from the Worldclim website. A Bayesian spatio-temporal conditional
      autoregressive model was used to quantify the relationship between monthly dengue
      cases and temperature, precipitation and elevation. RESULTS: Monthly dengue
      counts decreased by 18% (95% credible interval (CrI): 17-19%) in 2008 and
      increased by 30% (95% CrI: 28-31%) and 326% (95% CrI: 322-331%) in 2009 and 2010,
      respectively, compared to 2007. Additionally, there was a significant, nonlinear
      effect of monthly average precipitation. CONCLUSIONS: The results highlight the
      role of environmental risk factors in determining the spatial of dengue and show
      how these factors can be used to develop and refine preventive approaches for
      dengue in Colombia.

PMID- 24862216
TI  - An investigation into the effects of temporal resolution on hepatic dynamic
      contrast-enhanced MRI in volunteers and in patients with hepatocellular
      carcinoma.
AB  - This study investigated the effect of temporal resolution on the dual-input
      pharmacokinetic (PK) modelling of dynamic contrast-enhanced MRI (DCE-MRI) data
      from normal volunteer livers and from patients with hepatocellular carcinoma.
      Eleven volunteers and five patients were examined at 3 T. Two sections, one
      optimized for the vascular input functions (VIF) and one for the tissue, were
      imaged within a single heart-beat (HB) using a saturation-recovery fast gradient
      echo sequence. The data was analysed using a dual-input single-compartment PK
      model. The VIFs and/or uptake curves were then temporally sub-sampled (at
      interval ?t = [2-20] s) before being subject to the same PK analysis. Statistical
      comparisons of tumour and normal tissue PK parameter values using a 5%
      significance level gave rise to the same study results when temporally sub
      sampling the VIFs to HB < ?t <4 s. However, sub-sampling to ?t > 4 s did
      adversely affect the statistical comparisons. Temporal sub-sampling of just the
      liver/tumour tissue uptake curves at ?t <= 20 s, whilst using high temporal
      resolution VIFs, did not substantially affect PK parameter statistical
      comparisons. In conclusion, there is no practical advantage to be gained from
      acquiring very high temporal resolution hepatic DCE-MRI data. Instead the high
      temporal resolution could be usefully traded for increased spatial resolution or
      SNR. 

PMID- 24862215
TI  - A compartmental pharmacokinetic evaluation of long-acting rilpivirine in HIV
      negative volunteers for pre-exposure prophylaxis.
AB  - Rilpivirine long-acting (RPV-LA) is a parenteral formulation enabling prolonged
      plasma exposure. We explored its multiple-compartment pharmacokinetics (PK) after
      a single dose, for pre-exposure prophylaxis. Sixty-six HIV-negative volunteers
      were enrolled: women received an intramuscular dose of 300, 600, or 1,200 mg,
      with plasma and genital levels measured to 84 days postdose; men receiving 600 mg
      had similar PK determined in plasma and rectum. Ex vivo antiviral activity of
      cervicovaginal lavage (CVL) was also assessed. After a single dose, RPV
      concentrations peaked at days 6-8 and were present in plasma and genital-tract
      fluid to day 84. Vaginal and male rectal tissue levels matched those in plasma.
      At the 1,200 mg dose, CVL showed greater antiviral activity, above baseline, at
      days 28 and 56. All doses were well tolerated. All doses gave prolonged plasma
      and genital-tract rilpivirine exposure. PK and viral inhibition of repeated doses
      will be important in further dose selection.

PMID- 24862217
TI  - Bioinformatic identification and experimental validation of miRNAs from foxtail
      millet (Setaria italica).
AB  - MiRNAs are a novel group of non-coding small RNAs that negatively regulate gene
      expression. Many miRNAs have been identified and investigated extensively in
      plant species with sequenced genomes. However, few miRNAs have been identified in
      foxtail millet (Setaria italica), which is an ancient cereal crop of great
      importance for dry land agriculture. In this study, 271 foxtail millet miRNAs
      belonging to 44 families were identified using a bioinformatics approach. Twenty
      three pairs of sense/antisense miRNAs belonging to 13 families, and 18 miRNA
      clusters containing members of 8 families were discovered in foxtail millet. We
      identified 432 potential targets for 38 miRNA families, most of which were
      predicted to be involved in plant development, signal transduction, metabolic
      pathways, disease resistance, and environmental stress responses. Gene ontology
      (GO) analysis revealed that 101, 56, and 23 target genes were involved in
      molecular functions, biological processes, and cellular components, respectively.
      We investigated the expression patterns of 43 selected miRNAs using qRT-PCR
      analysis. All of the miRNAs were expressed ubiquitously with many exhibiting
      different expression levels in different tissues. We validated five predicted
      targets of four miRNAs using the RNA ligase mediated rapid amplification of cDNA
      end (5'-RLM-RACE) method. 

PMID- 24862218
TI  - Associations study of vitamin D receptor gene polymorphisms with diabetic
      microvascular complications: a meta-analysis.
AB  - BACKGROUND: Emerging evidence from preclinical and clinical studies has shown
      that vitamin D plays an important role in the pathogenesis of diabetic
      microvascular complications (DMI). Several potentially functional polymorphisms
      (ApaI, BsmI, FokI and TaqI) of vitamin D receptor (VDR) gene have been implicated
      in DMI risk, but individually published studies showed inconclusive results. The
      aim of this study was to quantitatively summarize the association between VDR
      polymorphisms and DMI risk. METHODS: We searched all the publications about the
      associations mentioned as above from PubMed and ISI database updated in December
      2013. Meta-analysis of the overall odds ratios (ORs) with 95% confidence
      intervals (CIs) was calculated with the fixed or random effect model. RESULTS:
      Eight studies involving 2734 subjects were included. Allelic and genotypic
      comparisons between cases and controls were evaluated. Overall analysis suggests
      that no significant association was observed among the ApaI, BsmI, FokI and TaqI
      variants and DMI risk in diabetic patients (all P values >0.05). In the
      stratified analysis, significant association was observed with diabetic
      nephropathy (DN) for VDR gene FokI polymorphism under a dominant model (OR 1.35,
      95% CI 1.05-1.74, P=0.02) in Caucasians. CONCLUSIONS: This meta-analysis
      indicated that the FokI polymorphism in VDR gene might affect individual
      susceptibility to DN in Caucasians. Further investigations are needed to confirm
      our results.

PMID- 24862219
TI  - KRT9 gene mutation as a reliable indicator in the prenatal molecular diagnosis of
      epidermolytic palmoplantar keratoderma.
AB  - Epidermolytic palmoplantar keratoderma (EPPK) is the most frequent form of such
      keratodermas. It is inherited in an autosomal dominant pattern and is clinically
      characterized by diffuse yellowish thickening of the skin on the palms and soles
      with erythematous borders during the first weeks or months after birth. EPPK is
      generally caused by mutations of the KRT9 gene. More than 26 KRT9 gene mutations
      responsible for EPPK have been described (Human Intermediate Filament Database,
      www.interfil.org), and many of these variants are located within the highly
      conserved coil 1A region of the alpha-helical rod domain of keratin 9.
      Unfortunately, there is no satisfactory treatment for EPPK. Thus, prenatal
      molecular diagnosis or pre-pregnancy diagnosis is crucial and benefits those
      affected who seek healthy descendants. In the present study, we performed
      amniotic fluid-DNA-based prenatal testing for three at-risk pregnant EPPK women
      from three unrelated southern Chinese families who carried the KRT9 missense
      mutations p.Arg163Trp and p.Arg163Gln, and successfully helped two families to
      bear normal daughters. We suggest that before the successful application of
      preimplantation genetic diagnosis (PGD), and noninvasive prenatal diagnosis of
      EPPK that analyzes fetal cells or cell-free DNA in maternal blood, prenatal
      genetic diagnosis by amniocentesis or chorionic villus sampling (CVS) offers a
      quite acceptable option for EPPK couples-at-risk to avoid the birth of affected
      offspring, especially in low- and middle-income countries.

PMID- 24862220
TI  - Glucocorticoid receptor in prostate epithelia is not required for corticosteroid
      induced epithelial hyperproliferation in the mouse prostate.
AB  - BACKGROUND: Glucocorticoids are used as a last resort treatment for prostate
      cancer but the cell-specific glucocorticoid receptor (GR) mediated actions and
      the role of endogenous glucocorticoids in prostate are not understood. METHODS:
      We evaluated the influence of prostate epithelial GR mediated actions of
      glucocorticoids in prostate structural development by comparing the intact wild
      type (WT) and prostate epithelia selective GR knockout (peGRKO) males at 8, 20,
      and 35 weeks of age. We also determined the cell-specific role of GR on
      corticosterone treatment induced prostate abnormalities by treating peGRKO and WT
      male mice with corticosterone depot pellets or placebo for 4 weeks. RESULTS: GR
      was not expressed in the epithelial cells of peGRKO prostate unlike WT but was
      expressed in stromal of both peGRKO and WT mice. Nevertheless, prostate weights,
      histological appearance, and secretory protein probasin expression in peGRKO were
      no different from WT. Despite lacking epithelial GR, the peGRKO prostate
      demonstrated corticosterone treatment induced hyperplasia similar to WT
      suggesting that stromal rather than epithelial GR mediates the hyperproliferative
      mouse prostate response to corticosterone. As circulating androgen levels were
      not affected by corticosterone treatment, this effect is likely to be mediated
      directly via prostate GR. CONCLUSIONS: Sustained administration of corticosterone
      induces prostate hyperplasia, which is mediated via GR expressed predominantly in
      the stroma. Thus GR mediated actions in the prostate may have significant cell
      specific effects that could be utilized for more rational therapeutic approaches
      in prostate cancer treatment. This also illustrates the paracrine hormonal
      mechanisms in prostate pathophysiology.

PMID- 24862222
TI  - Sympatric cryptic species in the crinoid genus Cenolia (Echinodermata: Crinoidea:
      Comasteridae) delineated by sequence and microsatellite markers.
AB  - The marine species of the southern coast of Australia have not been well studied
      with regard to molecular connectivity. Cryptic species are expected to be
      prevalent on this coastline. Here, we investigate the crinoid genus Cenolia
      (Echinodermata: Crinoidea: Comasteridae) using molecular methods to elucidate
      cryptic species and phylogenetic relationships. The genus Cenolia dominates the
      southern Australian crinoid fauna in shallow waters. Few studies have examined
      crinoids for cryptic species at a molecular level and these have been
      predominantly based on mitochondrial data. We employ the nuclear markers 28S rRNA
      and ITS-2 in addition to the mitochondrial COI. Six divergent mitochondrial
      clades were identified. Gene flow between confirmed clades was subsequently
      examined by the use of six novel microsatellite markers, showing that sympatric
      taxa with low mtDNA divergences (1.7% K2P) were not interbreeding in the wild.
      The type specimens of Cenolia benhami and C. spanoschistum were examined, as well
      as all six divergent clades. Morphological characters dividing taxa were refined.
      Due to comb pinnule morphology, the New Zealand species benhami was determined to
      belong to the genus Oxycomanthus (nov. comb.). Three new species of Cenolia
      (including the Australian "benhami") require description. 

PMID- 24862223
TI  - Phylogenetics, ancestral state reconstruction, and a new infrafamilial
      classification of the pantropical Ochnaceae (Medusagynaceae, Ochnaceae s.str.,
      Quiinaceae) based on five DNA regions.
AB  - Ochnaceae s.str. (Malpighiales) are a pantropical family of about 500 species and
      27 genera of almost exclusively woody plants. Infrafamilial classification and
      relationships have been controversial partially due to the lack of a robust
      phylogenetic framework. Including all genera except Indosinia and Perissocarpa
      and DNA sequence data for five DNA regions (ITS, matK, ndhF, rbcL, trnL-F), we
      provide for the first time a nearly complete molecular phylogenetic analysis of
      Ochnaceae s.l. resolving most of the phylogenetic backbone of the family. Based
      on this, we present a new classification of Ochnaceae s.l., with Medusagynoideae
      and Quiinoideae included as subfamilies and the former subfamilies Ochnoideae and
      Sauvagesioideae recognized at the rank of tribe. Our data support a monophyletic
      Ochneae, but Sauvagesieae in the traditional circumscription is paraphyletic
      because Testulea emerges as sister to the rest of Ochnoideae, and the next clade
      shows Luxemburgia+Philacra as sister group to the remaining Ochnoideae. To avoid
      paraphyly, we classify Luxemburgieae and Testuleeae as new tribes. The African
      genus Lophira, which has switched between subfamilies (here tribes) in past
      classifications, emerges as sister to all other Ochneae. Thus, endosperm-free
      seeds and ovules with partly to completely united integuments (resulting in an
      apparently single integument) are characters that unite all members of that
      tribe. The relationships within its largest clade, Ochnineae (former Ochneae),
      are poorly resolved, but former Ochninae (Brackenridgea, Ochna) are polyphyletic.
      Within Sauvagesieae, the genus Sauvagesia in its broad circumscription is
      polyphyletic as Sauvagesia serrata is sister to a clade of Adenarake, Sauvagesia
      spp., and three other genera. Within Quiinoideae, in contrast to former
      phylogenetic hypotheses, Lacunaria and Touroulia form a clade that is sister to
      Quiina. Bayesian ancestral state reconstructions showed that zygomorphic flowers
      with adaptations to buzz-pollination (poricidal anthers), a syncarpous gynoecium
      (a near-apocarpous gynoecium evolved independently in Quiinoideae and Ochninae),
      numerous ovules, septicidal capsules, and winged seeds with endosperm are the
      ancestral condition in Ochnoideae. Although in some lineages poricidal anthers
      were lost secondarily, the evolution of poricidal superstructures secured the
      maintenance of buzz-pollination in some of these genera, indicating a strong
      selective pressure on keeping that specialized pollination system. 

PMID- 24862221
TI  - The origin and diversification of the merozoite surface protein 3 (msp3) multi
      gene family in Plasmodium vivax and related parasites.
AB  - The genus Plasmodium is a diversified group of parasites with more than 200 known
      species that includes those causing malaria in humans. These parasites use
      numerous proteins in a complex process that allows them to invade the red blood
      cells of their vertebrate hosts. Many of those proteins are part of multi-gene
      families; one of which is the merozoite surface protein-3 (msp3) family. The msp3
      multi-gene family is considered important in the two main human parasites,
      Plasmodium vivax and Plasmodium falciparum, as its paralogs are simultaneously
      expressed in the blood stage (merozoite) and are immunogenic. There are large
      differences among Plasmodium species in the number of paralogs in this family.
      Such differences have been previously explained, in part, as adaptations that
      allow the different Plasmodium species to invade their hosts. To investigate
      this, we characterized the array containing msp3 genes among several Plasmodium
      species, including P. falciparum and P. vivax. We first found no evidence
      indicating that the msp3 family of P. falciparum was homologous to that of P.
      vivax. Subsequently, by focusing on the diverse clade of nonhuman primate
      parasites to which P. vivax is closely related, where homology was evident, we
      found no evidence indicating that the interspecies variation in the number of
      paralogs was an adaptation related to changes in host range or host switches.
      Overall, we hypothesize that the evolution of the msp3 family in P. vivax is
      consistent with a model of multi-allelic diversifying selection where the
      paralogs may have functionally redundant roles in terms of increasing antigenic
      diversity. Thus, we suggest that the expressed MSP3 proteins could serve as
      "decoys", via antigenic diversity, during the critical process of invading the
      host red blood cells. 

PMID- 24862224
TI  - Uncovering sibling species in Radiolaria: evidence for ecological partitioning in
      a marine planktonic protist.
AB  - Phylogeography of unicellular plankton, as representative pelagic organisms, is
      fundamental to understanding their evolution in the ocean. Historically, these
      microplankton were believed to have cosmopolitan distributions achieved through
      passive transport and little potential for speciation because of a lack of
      geographic barriers in the oceans. Recent phylogeographic studies of these
      microplankton, however, have often revealed high diversity and fine-scale
      geographic distributions. These apparent contradictions may result from poor
      knowledge of the spatial distributions of pelagic microplankton in the water
      column. More information about both geographic and vertical distributions of
      pelagic populations could reveal the dispersal pathways, gene flow, and resulting
      diversifications in the open ocean. Here we demonstrate that two genetic types of
      the radiolarian morphospecies Spongotrochus glacialis with morphological
      differences are vertically segregated into the upper and lower surface waters
      within the pycnocline of the North Pacific Subtropical Water. This vertically
      separated distribution of two sister species is associated with distinct
      ecological partitioning. These two species could survive on different food
      resources from their respective environments: one in oligotrophic surface waters
      by using nutrients from symbionts, and the other at greater depths by depending
      on both heterotrophic and symbiotic nutrition. Moreover, molecular divergence
      time estimates suggest that the two species diverged during the period of
      oligotrophic surface-water development in the Pacific Ocean. Our findings suggest
      that genetic isolation in the vertical dimension occurs through ecological
      partitioning even in the absence of physical barriers in the pelagic oceans. 

PMID- 24862225
TI  - Retrospective evaluation of phacoemulsification and aspiration in 41 horses (46
      eyes): visual outcomes vs. age, intraocular lens, and uveitis status.
AB  - OBJECTIVE: To determine the effect of age at the time of surgery, intraocular
      lens (IOL) placement, and presence of chronic uveitis on visual outcome after
      phacoemulsification and aspiration (PA) of cataracts in horses. ANIMALS STUDIED:
      Records of 41 horses (46 eyes) receiving unilateral or bilateral PA. METHODS:
      Retrospective analysis of horses receiving unilateral or bilateral PA at the NCSU
      VTH (35 horses, 39 eyes) and in Northern Italy (six horses, seven eyes) was
      performed. Visual status at last follow-up was compared to age at the time of
      surgery, IOL status, and presence of chronic uveitis preoperatively. Seven horses
      with chronic uveitis also underwent placement of a suprachoroidal cyclosporine
      implant. Clinical ophthalmic examinations and owner questionnaires were used to
      evaluate visual status. RESULTS: Twenty-one of 46 eyes (46%) received an IOL and
      12 of 46 eyes (26%) had chronic uveitis. Overall, 25 of 46 eyes (54%) were visual
      at last follow-up (mean 35.1 +/- 34.8 months). Age (mean 8.6 +/- 7.7 years) was
      not significantly associated with visual outcome. Fourteen of 21 (67%)
      pseudophakic eyes and 11 of 25 (44%) aphakic eyes were visual at last follow-up
      (P = 0.342). Eyes with preoperative chronic uveitis were significantly less
      likely to be visual (3 of 12 eyes [25%]) than horses without preoperative chronic
      uveitis (22 of 34 eyes [65%]) (P = 0.023). CONCLUSIONS: Horses with chronic
      uveitis had significantly less favorable visual outcome after PA. Older age at
      surgery and IOL use were not associated with poor visual outcome.

PMID- 24862226
TI  - Lung cryobiopsies: a paradigm shift in diagnostic bronchoscopy?
AB  - In 1963, the first bronchoscopic lung biopsy was performed. Less than 10 years
      later, the technique of transbronchial lung biopsy using a flexible bronchoscope
      was introduced into clinical practice, significantly reducing the rate of major
      complications and the rate of surgical lung biopsies in patients with diffuse
      parenchymal lung diseases. The diagnostic yield of transbronchial lung biopsy
      varies among various parenchymal lung diseases. In pulmonary sarcoidosis and
      lymphangitis carcinomatosa, a diagnosis can be obtained in up to 80% of patients.
      This method is considered inadequate, however, in identifying more complex
      histological patterns such as usual interstitial pneumonitis or nonspecific
      interstitial pneumonitis. Introduction of the 'jumbo forceps' and of a more
      'surgically oriented' procedural setting (patients deeply sedated and intubated)
      allowed larger and more numerous lung specimens to be obtained without a
      significant increase of complications such as pneumothorax or bronchial bleeding.
      However, the possibility to obtain enough parenchymal tissue for a morphological
      diagnosis of complex patterns remained unmet. Recently, the use of cryoprobes has
      achieved a significant impact on this issue allowing to obtain large quantity of
      tissue. Recent studies document that with transbronchial cryobiopsies the
      diagnosis of usual interstitial pneumonitis can be made confidently by
      pathologists with a good inter-observer agreement. Pneumothorax is the main
      complication (reported in up to one fourth of cases in some series); bronchial
      bleeding is easily controlled using Fogarty balloon. Transbronchial cryobiopsy is
      a promising new technique that may become a valid alternative to surgical lung
      biopsy in the near feature. 

PMID- 24862227
TI  - Fetal hemodynamic changes in pregnant women with influenza AH1N1 infection and
      reduced arterial partial pressure of oxygen.

PMID- 24862228
TI  - ORF005L from infectious spleen and kidney necrosis virus is located in the inner
      mitochondrial membrane and induces apoptosis.
AB  - Infectious spleen and kidney necrosis virus (ISKNV) belongs to the genus
      Megalocytivirus in the family Iridoviridae. This virus is the etiological agent
      of a serious and pandemic disease in fish. Cells infected with ISKNV undergo
      apoptosis. In this study, the ISKNV ORF005L gene was characterized and
      functionally investigated. Bioinformatics analysis revealed that the ORF005L
      protein contains a region similar to the catalytic domain of CTD-like
      phosphatases. Real-time quantitative-PCR results showed the transcription profile
      of ORF005L in ISKNV-infected cells; in these cells, ORF005L was initially
      transcribed at 24 h post-infection. The green fluorescent protein-tagged ORF005L
      protein was localized in the mitochondria. Sub-mitochondrial fractions were
      subjected to Western blot, and the results showed that ORF005L was specifically
      located in the inner membrane of the mitochondria. The ORF005L in fathead minnow
      cells was transiently expressed, resulting in the decrease in mitochondrial
      transmembrane potential, which induced cell apoptosis. ORF005L was knocked down
      by specific dsRNA, thereby significantly reducing the apoptosis of mandarin fish
      fry-1 cells induced by ISKNV infection. These results indicated that the ORF005L
      of ISKNV could disrupt mitochondrial function and cause apoptosis. This study may
      provide novel insights into the pathogenesis of Megalocytivirus infection. 

PMID- 24862229
TI  - The risk factors of avascular necrosis in patients with systemic lupus
      erythematosus: a meta-analysis.
AB  - The aim of this study was to determine the risk factors for avascular necrosis
      (AVN) in patients with systemic lupus erythematosus (SLE). Four electronic
      databases (PubMed, EMBASE, Ovid, and Science Direct) were searched for. The
      search was performed to identify the articles as to SLE with AVN before September
      2013. The clinical and laboratory data were extracted, and a meta-analysis was
      performed to identify the risk factors for AVN in patients with SLE. Publication
      bias was assessed with funnel plot and Egger's test. A total of 995 papers were
      found from the four databases; 16 studies were finally included. Pooled analysis
      showed the following result. The result showed that arthritis (odds ratio
      (OR)=2.448, 95 % confidence interval (CI)=1.617-3.707), cushingoid (OR=3.890, 95
      % CI=1.591-9.510), gastrointestinal involvement (OR=2.054, 95 % CI=1.283-3.290),
      hypertension (OR=1.482, 95 % CI=1.093-2.008), oral ulcers (OR=1.877, 95 %
      CI=1.182-2.979), pleuritis (OR=2.302, 95 % CI=1.325-4.001), renal disease
      (OR=1.475, 95 % CI=1.124-1.936), and vasculitis (OR=2.591, 95 % CI=1.358-4.944)
      were relevant with AVN in SLE patients. Cytotoxic drug (OR=1.834, 95 % CI=1.065
      3.156, P=0.029), the total cumulative dose (Standard Mean Difference (SMD) =
      1.104, 95 % CI = 0.118-2.090, P = 0.028), maximum daily dose (SMD = 0.484, 95 %
      CI = 0.288-0.678, P < 0.001), and mean daily dose (SMD=1.305, 95 % CI=0.061
      2.549, P=0.040) were significantly higher in AVN group. There were no
      significantly laboratory features that appeared in this pooled analysis. We
      conclude that arthritic, cushingoid, gastrointestinal involvement, hypertension,
      oral ulcers, pleuritis, renal disease, vasculitis, cytotoxic drug, and steroid
      treatment may contribute to AVN in SLE patients.

PMID- 24862230
TI  - Survey of hospital procedures for parapneumonic effusion in children highlights
      need for standardised management.
AB  - AIM: This study sought to evaluate the initial management of children with
      parapneumonic effusion admitted to all French university hospitals. METHODS: A
      nationwide survey of all 35 university hospitals took place in 2011 to assess
      practices for children with parapneumonic effusion, using a hypothetical clinical
      vignette and a standardised questionnaire. Two to four paediatricians per
      hospital were interviewed and asked about their initial management, probabilistic
      antibiotic therapy and its adaptation to microbiological results and subsequent
      course. Answers from paediatricians working in emergency departments, intensive
      care units and conventional paediatric units were compared. RESULTS: Of the 100
      paediatricians contacted, 95 responded. Of these, 98% would order an initial
      blood test, 70% would order diagnostic thoracentesis, and all would start
      immediate antibiotic therapy: 31% with a single drug, 67% with two drugs and 2%
      with three drugs. The most frequent initial choices were third-generation
      cephalosporin alone (17%) or combined with rifampicin (34%) or vancomycin (24%).
      Adaptation varied according to drug used, dose and duration, especially when the
      microorganism was not Streptococcus pneumoniae. Practices did not differ
      significantly among the different groups of paediatricians. CONCLUSION:
      Standardised management of parapneumonic effusion, including routine
      thoracentesis and more consistent prescription of antibiotics, is needed.

PMID- 24862231
TI  - Implicit measurements of sexual preference in self-declared heterosexual men: a
      pilot study on the rate of androphilia in Italy.
AB  - INTRODUCTION: An unambiguous measurement of the rate of nonheterosexuality in the
      male population (male bisexuality and homosexuality) is essential to estimate the
      health risks associated with same-sex sexual behavior and to scale social and
      health programs for these citizens. However, self-reported questionnaires on
      explicit measures of sexual orientation yield significant underestimations of
      nonheterosexuality. A necessary prerequisite for nonheterosexual preference is
      androphilia (sexual-erotic attraction to males), which can be explored through
      psychological tests. AIMS: This study, using a pilot sample, investigates the
      possibility to inventory the frequency of male androphilia in the general
      population through a sexual preference implicit association test (sp-IAT). This
      test is a classical IAT that is based on an association of pictures and words and
      is easily portable. METHODS: First we conducted a preliminary validation of the
      specific IAT protocol on 24 control subjects; then, we examined a sample of 150
      adult males in Italy as a pilot study. The subjects responded to the sp-IAT and
      completed the explicit Kinsey scale questionnaire. MAIN OUTCOME MEASURES: Kinsey
      scale scores and D value of sp-IAT for both preliminary and pilot sample.
      RESULTS: On the explicit Kinsey scale, 2.7% of the sample declared themselves to
      be sexually attracted to men, corresponding to previous explicit samplings of the
      Italian homosexual male population. However, the sp-IAT identified that 11.3% of
      self-declared gynephilic heterosexuals showed a moderate to strong androphilia
      with a significant effect size (D) always below -0.2, and another 5.6% of the
      heterosexual sample showed no preference for females (D between -0.2 and 0).
      CONCLUSION: The Kinsey questionnaire strongly dichotomized the responses as
      either attracted to females or attracted to men, whereas the sp-IAT showed a
      wider distribution of responses from gynephilia to androphilia. In conclusion,
      the sp-IAT could be a novel and unambiguous instrument useful to ascertain
      androphilia population prevalence as a proxy for possible male
      nonheterosexuality. Camperio Ciani A and Battaglia U. Implicit measurements of
      sexual preference in self-declared heterosexual men: A pilot study on the rate of
      androphilia in Italy. J Sex Med 2014;11:2207-2217.

PMID- 24862233
TI  - Asymmetric epoxidation of cis/trans-beta-methylstyrene catalysed by immobilised
      Mn(salen) with different linkages: heterogenisation of homogeneous asymmetric
      catalysis.
AB  - Immobilised Mn(salen) catalysts with two different linkages were studied in the
      asymmetric epoxidation of cis/trans-beta-methylstyrene using NaClO as oxidant.
      The immobilised Mn(salen) complexes inside nanopores can lead to different
      catalytic behaviour compared with that of homogeneous Jacobsen catalyst. The
      rigidity of the linkage was found to be a key factor affecting the catalytic
      performance of immobilised catalysts. The immobilised catalyst with a rigid
      linkage exhibited comparable chemical selectivity, enantioselectivity and
      cis/trans ratio of product formation to that obtained with homogeneous Jacobsen
      catalysts. In contrast, the immobilised catalyst with a flexible linkage gave
      remarkably lower chemical selectivity, enantioselectivity and inverted cis/trans
      ratio compared with the results obtained with the homogeneous Jacobsen catalyst
      and the immobilised catalyst with rigid linkage. Thus, for immobilised Mn(salen)
      catalysts, a rigid linkage connecting active centres to the support is essential
      to obtain activity and enantioselectivity as high as those obtained in
      homogeneous systems. 

PMID- 24862232
TI  - Biphasic ferrogels for triggered drug and cell delivery.
AB  - Ferrogels are an attractive material for many biomedical applications due to
      their ability to deliver a wide variety of therapeutic drugs on-demand. However,
      typical ferrogels have yet to be optimized for use in cell-based therapies, as
      they possess limited ability to harbor and release viable cells. Previously, an
      active porous scaffold that exhibits large deformations and enhanced biological
      agent release under moderate magnetic fields has been demonstrated.
      Unfortunately, at small device sizes optimal for implantation (e.g., 2 mm
      thickness), these monophasic ferrogels no longer achieve significant deformation
      due to a reduced body force. A new biphasic ferrogel, containing an iron oxide
      gradient, capable of large deformations and triggered release even at small gel
      dimensions, is presented in this study. Biphasic ferrogels demonstrate increased
      porosity, enhanced mechanical properties, and potentially increased
      biocompatibility due to their reduced iron oxide content. With their ability to
      deliver drugs and cells on-demand, it is expected that these ferrogels will have
      wide utility in the fields of tissue engineering and regenerative medicine. 

PMID- 24862234
TI  - Targeted patient education: does it improve outcome of minimally invasive breast
      biopsy?

PMID- 24862235
TI  - Oral sarcoidosis: a case report and review of the literature.
AB  - Sarcoidosis is a chronic multi-system immuno-inflammatory disorder characterized
      by non-caseating granulomatous infiltration of affected tissues that may result
      in fibrosis and organ dysfunction. It generally affects genetically predisposed
      young adults who develop a local dysregulated cell-mediated immune response
      towards an undefined 'sarcoidal antigen'. From recent data, it has become evident
      that Propionibacterium acnes and Mycobacterium tuberculosis are the probable
      antigenic agents which initiate sarcoidosis. Oral sarcoidosis is rare with only
      about 70 cases having been reported in the literature. The purpose of this report
      is to present a case of oral and cutaneous sarcoidosis in a black female that was
      probably triggered by mycobacteria. 

PMID- 24862236
TI  - Proinflammatory effect of trivalent arsenical species in a co-culture of Caco-2
      cells and peripheral blood mononuclear cells.
AB  - Chronic exposure to inorganic arsenic (As) is associated with type 2 diabetes,
      cardiovascular diseases and cancer. Ingested inorganic As is transformed within
      the gastrointestinal tract and can give rise to more toxic species such as
      monomethylarsonous acid [MMA(III)] and dimethylarsinous acid [DMA(III)]. Thus,
      the intestinal epithelium comes into contact with toxic arsenical species, and
      the effects of such exposure upon epithelial function are not clear. The present
      study has evaluated the effect of 1 uM arsenite [As(III)], 0.1 uM MMA(III) and 1
      uM DMA(III) upon the release of cytokines [interleukin-6 (IL6), IL8, tumor
      necrosis factor alpha (TNFalpha)], using a compartmentalized co-culture model
      with differentiated Caco-2 cells in the apical compartment and peripheral blood
      mononuclear cells in the basolateral compartment. In addition, the combined
      effect of arsenical species and lipopolysaccharide (LPS), both added into the
      apical compartment, has been analyzed. The results indicate that exposure to the
      arsenical forms induces a proinflammatory response. An increase in cytokine
      secretion into the basolateral compartment was observed, particularly as regards
      TNFalpha (up to 1,600 %). The cytokine levels on the apical side also increased,
      though to a lesser extent. As/LPS co-exposure significantly affected the
      proinflammatory response as compared to treatment with As alone. Treatment with
      DMA(III) and As/LPS co-exposure increased the permeability of the intestinal
      monolayer. In addition, As/LPS treatments enhanced As(III) and MMA(III) transport
      through the intestinal monolayer.

PMID- 24862237
TI  - Absence of EGFR, ERBB2 and ERBB4 mutation homologous to the oncogenic ERBB3 Val
      104 mutation in colorectal cancers.

PMID- 24862238
TI  - (68)Ga-DOTATATE PET/CT in the evaluation of patients with neuroendocrine
      metastatic carcinoma of unknown origin.
AB  - OBJECTIVE: There is little evidence regarding the role of (68)Ga-DOTATATE PET/CT
      for the identification of primary tumors in patients with metastatic
      neuroendocrine carcinoma of unknown primary. The aim of this study is to assess
      the value of this technique in the mentioned clinical scenario. METHODS: We
      retrospectively studied twenty-nine patients (mean age 59.5 +/- 10.6 years;
      female 17) with pathologically proven neuroendocrine metastases. In all cases
      conventional imaging was negative for primary tumor identification. (68)Ga
      DOTATATE PET/CT was performed with a mean dose of 104.2 +/- 18.8 MBq, using a 64
      slice PET/CT with time-of-flight correction. A team of an experienced radiologist
      and a nuclear medicine physician evaluated the images. The maximum SUV (SUVm) was
      measured in all abnormal foci. Histopathology (when available) and/or clinical
      follow-up with correlative imaging was considered as reference standard. RESULTS:
      (68)Ga-DOTATATE PET/CT identified the primary tumor in 17/29 (59%) patients in
      the following locations: pancreas (n = 7), ileum (n = 7), duodenum (n = 1), colon
      (n = 1) and stomach (n = 1). In this population a significant correlation was
      found between SUVm of primary tumor and metastases (r = 0.815, P < 0.0001).
      Furthermore, additional sites of unsuspected metastases were demonstrated in 9
      patients of this group and in 6 patients in whom no primary tumor was localized,
      mainly in lymph nodes and mesentery. Pathology confirmation was obtained in 7
      patients who underwent surgery, whereas in the remaining 10 patients, correlative
      imaging and follow-up confirmed primary tumor localization. CONCLUSIONS: (68)Ga
      DOTATATE PET/CT is a clinically useful imaging technique for the localization of
      primary tumors in patients with neuroendocrine metastatic carcinoma of unknown
      origin with the potential of having a significant impact in patient management
      and therapy planning.

PMID- 24862239
TI  - Research in practice: substance P antagonism in chronic pruritus.
AB  - Pruritus is an unpleasant sensation of the skin, which triggers a desire to
      scratch or rub. The chronic form (>=6 weeks' duration) often occurs as a side
      effect of many diseases and is usually accompanied by a high loss in quality of
      life for patients, especially in cases in which the symptom is chronic without
      adequate treatment options. In recent years, the situation improved continuously,
      guidelines for chronic pruritus have been defined and standard medications have
      been proposed. For many reasons, there are still patients who are unable to
      obtain relief. New therapeutic approaches are therefore urgently needed. Blocking
      the neuropeptide substance P is a promising strategy; substance P mediates
      clinically relevant pro-inflammatory effects by binding to the neurokinin 1
      receptor (NK-1R). This led us to hypothesize that NK-1R antagonists are promising
      therapeutic options for chronic pruritus. Several international case series have
      meanwhile proven the antipruritic effect of the NK-1R antagonist aprepitant for
      various forms of chronic pruritus. Initiation of clinical trials with new NK-1R
      antagonists as a new therapeutic option continues this trend.

PMID- 24862240
TI  - Impact of an acceptance facilitating intervention on diabetes patients'
      acceptance of Internet-based interventions for depression: a randomized
      controlled trial.
AB  - AIMS: To (1) determine diabetes patients' acceptance of Internet-based
      interventions (IBIs) for depression, to (2) examine the effectiveness of an
      acceptance facilitating intervention (AFI) and to (3) explore subgroup specific
      effects. METHODS: 141 diabetes patients from two inpatient rehabilitation units
      and one outpatient clinic in Germany were randomly allocated to an intervention
      (IG) and a no-intervention control group (CG). The IG received an AFI consisting
      of a personal information session before filling-out a questionnaire on patients'
      acceptance of IBIs, predictors of acceptance (performance expectancy, effort
      expectancy, social influence, facilitating conditions, and Internet anxiety) as
      well as sociodemographic, depression-related and diabetes-related variables. The
      CG filled out the questionnaire immediately. Patients' acceptance of IBIs was
      measured with a four-item scale (sum-score ranging from 4 to 20). RESULTS: The CG
      showed a low (50.7%) to medium (40.8%) acceptance with only 8.5% of all diabetes
      patients reporting a high acceptance of IBIs for depression. The AFI had no
      significant effect on acceptance (IG: M=10.55, SD=4.69, n=70; KG: M=9.65,
      SD=4.27, n=71; d=0.20 [95%-CI: -0.13;0.53]) and the predictors of acceptance.
      Yet, subgroup analyses yielded a trend for depressed, diabetes-related
      distressed, female and younger (<59) participants and for those who do not
      frequently use the Internet to profit from the AFI. CONCLUSION: Diabetes patients
      show a rather low acceptance toward IBIs for depression. Findings indicate that
      the AFI is likely to be effective in the subgroup of depressed, diabetes-related
      distressed, female or younger diabetes patients, but not in the whole target
      population. Hence, AFIs might need to be tailored to the specific needs of
      subpopulations.

PMID- 24862241
TI  - Detecting cancer by breath volatile organic compound analysis: a review of array
      based sensors.
AB  - Cancer diagnosis is typically delayed to the late stages of disease due to the
      asymptomatic nature of cancer in its early stages. Cancer screening offers the
      promise of early cancer detection, but most conventional diagnostic methods are
      invasive and remain ineffective at early detection. Breath analysis is, however,
      non-invasive and has the potential to detect cancer at an earlier stage by
      analyzing volatile biomarkers in exhaled breath. This paper summarizes breath
      sampling techniques and recent developments of various array-based sensor
      technologies for breath analysis. Significant advancements were made by a number
      of different research groups in the development of nanomaterial-based sensor
      arrays, and the ability to accurately distinguish cancer patients from healthy
      controls based on the volatile organic compounds (VOCs) in exhaled breath has
      been demonstrated. Optical sensors based on colorimetric sensor array technology
      are also discussed, where preliminary clinical studies suggest that metabolic VOC
      profiles could be used to accurately diagnose various forms of lung cancer.
      Recent studies have demonstrated the potential of using metabolic VOCs for cancer
      detection, but further standardization and validation is needed before breath
      analysis can be widely adopted as a clinically useful tool. 

PMID- 24862243
TI  - Recurrence risk of low Apgar score among term singletons: a population-based
      cohort study.
AB  - OBJECTIVE: To examine the risk of recurrence of low Apgar score in a subsequent
      term singleton pregnancy. DESIGN: Population-based cohort study. SETTING: The
      Netherlands. POPULATION: A total of 190,725 women with two subsequent singleton
      term live births between 1999 and 2007. METHODS: We calculated the recurrence
      risk of low Apgar score after adjustment for possible confounders. Women with an
      elective cesarean delivery, fetus in breech presentation or a fetus with
      congenital anomalies were excluded. Results were reported separately for women
      with a vaginal delivery or a cesarean delivery at first pregnancy. MAIN OUTCOME
      MEASURES: Prevalence of birth asphyxia, a 5-min Apgar score <7. RESULTS: The risk
      for an Apgar score of <7 in the first pregnancy was 0.99% and overall halved in
      the subsequent pregnancies (0.50%). For those with asphyxia in the first
      pregnancy, the risk of recurrence of a low Apgar score in the subsequent
      pregnancy was 1.1% (odds ratio 2.1, 95% confidence interval 1.4-3.3). This
      recurrence risk was present in women with a previous vaginal delivery (odds ratio
      2.1, 95% confidence interval 1.2-3.5) and in women with a previous cesarean
      delivery (odds ratio 3.8, 95% confidence interval 1.7-8.5). Among women with a
      small-for-gestational-age infant in the subsequent pregnancy and a previous
      vaginal delivery, the recurrence risk was 4.8% (adjusted odds ratio 5.8, 95%
      confidence interval 2.0-16.5). CONCLUSION: Women with birth asphyxia of the first
      born have twice the risk of renewed asphyxia at the next birth compared to women
      without birth asphyxia of the first born. This should be incorporated in the risk
      assessment of pregnant women.

PMID- 24862244
TI  - Assessing resident surgical competency in urology using a global rating scale.
AB  - OBJECTIVE: Training programs must ensure residents are competent to practice
      independently. For surgical fields, this is generally done by the faculty who
      graduate the residents, but there has been no accepted methodology for this
      process. DESIGN: As part of a generalized survey, attending physicians performing
      an operation were asked to assess resident competency to perform the operation
      independently in an average patient, using a single global question. Residents,
      in a blinded manner, were asked to answer the same question. SETTING: Urology
      Residency Program, Albany Medical College, Albany, NY. PARTICIPANTS: Participants
      included 12 resident physicians and 10 attending physicians. RESULTS: There is a
      large variation in attending physician assessment of resident surgical
      competency, and the assessment varies by attending physician and by resident.
      Generally, attending physicians rated residents lower than the residents rated
      themselves. The discrepancy was largest for residents early in training and
      lessened as resident experience increased. Assessments also tended to converge
      toward the attending physician assessment as competency increased. Assessments
      had less variability when involving a single, high-volume procedure for a single
      resident. CONCLUSIONS: Assessing resident surgical competency with a standardized
      global question is feasible, but complex. Attending physicians and residents
      differ significantly in their assessment of resident competence. The trend of
      residents' perceptions approaching attending physician estimates as training and
      competence increases supports the current concept that program directors should
      use attending physician assessments as the primary measure.

PMID- 24862245
TI  - Are verbal intelligence subtests and reading measures immune to non-credible
      effort?
AB  - The validity of neuropsychological testing is reliant on examinees putting forth
      adequate effort, yet it has been asserted that verbal subtests from the Wechsler
      Adult Intelligence Scales (WAIS) are insensitive to suboptimal effort in
      comparison to other commonly used neuropsychological measures. The current study
      examined performance differences on the entire WAIS-IV and WRAT-4 Reading, as
      well as the CVLT-II and several WMS-IV subtests, in 207 Veterans classified into
      Credible Effort (n = 146) and Non-credible Effort (n = 61) groups. Analyses
      revealed that the Non-credible Effort group performed significantly lower on all
      examined measures including verbal tests, with moderate to large effect sizes
      observed for most tests. Current findings thus indicate that WAIS-IV verbal
      subtests and reading ability measures, such as on the WRAT-4, are not insensitive
      to effects of non-credible effort. Consequently it is recommended that these
      tests not generally be used to estimate baseline intellectual functioning when
      found in the presence of non-credible effort. While there was broad performance
      suppression across all measures examined, results also showed a distinct
      continuum of test susceptibility with some measures being more or less sensitive
      to inadequate effort. Recommendations for future performance validity test
      development are presented. 

PMID- 24862246
TI  - High-pressure SANS and fluorescence unfolding study of calmodulin.
AB  - Apo-calmodulin, a small soluble mainly alpha protein, is a calcium-dependent
      protein activator. Calcium binding affects the calmodulin conformation but also
      its stability. Calcium free form unfolds between 40 and 80 degrees C, whereas the
      calcium-saturated form is stable up to temperatures as high as 100 degrees C,
      forbidding comparison of the thermal unfolding pathways of the two forms. Thus,
      this paper focuses especially on the conformation of pressure-induced unfolding
      states of both forms of calmodulin, by combining small-angle neutron scattering
      (SANS) with biophysical techniques such as tyrosines and ANS fluorescence. In
      contrast to heat denaturation (Gibrat et al., BBA, 2012), the pressure
      denaturation of calmodulin is reversible up to pressures of 3000bar (300MPa). A
      pressure-induced compact intermediate state has been found for the two calmodulin
      forms, but their unfolding pathways are different. A domain compaction and an
      increase of the ANS fluorescence of holo form have been evidenced. On the
      contrary, a domain dilatation and an ANS fluorescence decrease have been found
      for the apo form. The pressure induced an increase of the interdomain distance
      for both calmodulin forms, suggesting that the central linker of calmodulin is
      flexible in solution. 

PMID- 24862247
TI  - Factors associated with clinical and structural outcomes after arthroscopic
      rotator cuff repair with a suture bridge technique in medium, large, and massive
      tears.
AB  - BACKGROUND: This study was conducted to evaluate clinical outcomes, maintenance
      of repair integrity, and retear rate after arthroscopic rotator cuff repair by a
      suture bridge technique among patients with medium, large, and massive rotator
      cuff tears. METHODS: We evaluated 147 patients who had undergone arthroscopic
      rotator cuff repair. Clinical and functional evaluations were performed with the
      Constant and University of California-Los Angeles scores. All patients were
      confirmed to have magnetic resonance imaging evidence of tendon healing at least
      12 months postoperatively. RESULTS: The average postoperative time to follow-up
      magnetic resonance imaging was 23.4 months (range, 12-48 months). A total of 25
      (17.0%) retears were observed. All clinical outcome scores were improved
      significantly at follow-up. Larger intraoperative tear sizes were correlated with
      higher retear rates. The incidence of retear was also higher in cases in which
      the preoperative fatty degeneration grade was higher. The incidence of retear
      increased with age and in the heavy worker group (e.g., farmers, carriers, car
      mechanics) but was not statistically significant. CONCLUSIONS: Arthroscopic
      rotator cuff repair by a suture bridge technique yields improvements in clinical
      outcome measures and a relatively high degree of patient satisfaction despite the
      fact that repair integrity is not maintained in many cases.

PMID- 24862248
TI  - Quantitative comparison of exposure for the posterior Judet approach to the
      scapula with and without deltoid takedown.
AB  - BACKGROUND: The purposes of this study are to quantify the extent of the scapula
      exposed and to describe the osseous landmarks within the dissection of a
      posterior Judet approach with and without takedown of the posterior deltoid
      muscle. METHODS: The posterior Judet approach using the muscular interval between
      the teres minor and infraspinatus muscle with and without takedown of the deltoid
      muscle was performed on 10 fresh-frozen cadaveric shoulders. Retractors with 2 kg
      of force were used at the wound margins for retraction. Upon completion of the
      exposure, a calibrated digital image was taken from the surgeon's perspective and
      specific anatomic landmarks were identified. The digital images were then
      analyzed with a computer software program, ImageJ (National Institutes of Health,
      Bethesda, MD, USA), to calculate the area (in square centimeters) of bone
      exposed. RESULTS: The mean area of posterior scapula exposed by the traditional
      Judet approach with takedown of the deltoid muscle was 30.2 cm(2) (95% confidence
      interval, 27.7-32.7 cm(2)) compared with 27.3 cm(2) (95% confidence interval,
      24.8-29.9 cm(2)) when the deltoid was not detached (P < .0001). In all 10
      cadaveric shoulders, the posterior Judet approach without takedown of the deltoid
      muscle allowed access to the posterior glenoid, lateral scapula border, and
      spinoglenoid notch. CONCLUSIONS: Although takedown of the deltoid muscle improves
      exposure, the posterior Judet approach without takedown of the posterior deltoid
      muscle allows for safe exposure to 91% of the bony scapula obtained by removing
      the deltoid muscle and access to the critical osseous fixation points of the
      posterior scapula.

PMID- 24862249
TI  - Morphologic features of humeral head and glenoid version in the normal
      glenohumeral joint.
AB  - BACKGROUND: The morphologic features and clinical significance of version of the
      humeral head and glenoid remain unclear. The purpose of this study was to
      evaluate the normal values of humeral head version and glenoid version on
      computed tomography scans and to clarify their features in the normal
      glenohumeral joint. METHODS: Images for analysis were computed tomography scans
      of 410 normal shoulders from healthy volunteers. Values of humeral head and
      glenoid version were measured. In glenoid version measurement, 3-dimensionally
      corrected slices were reconstructed to eliminate scapular inclination.
      Differences in humeral head version and glenoid version were assessed between
      dominant and nondominant shoulders and between men and women. Correlation
      analyses were also performed in the values of version between dominant and
      nondominant shoulders and between humeral head version and glenoid version.
      RESULTS: The values of humeral head retroversion were widely distributed from -2
      degrees  to 60 degrees , with an average of 26 degrees  +/- 11 degrees . Average
      glenoid retroversion was 1 degrees  +/- 3 degrees , ranging from -9 degrees  to
      13 degrees . Both humeral head retroversion and glenoid retroversion were
      significantly higher on the dominant side than on the nondominant side and
      significantly higher in men than in women. Humeral head version and glenoid
      version values were well correlated with those of the contralateral shoulder. No
      correlation was found between humeral head version and glenoid version.
      CONCLUSIONS: This study found differences in humeral head version and glenoid
      version by sex and shoulder dominance in a large sample. Both the humeral head
      and glenoid are thought to be more retroverted in high-demand shoulders.

PMID- 24862250
TI  - Radioulnar space available at the level of the biceps tuberosity for repaired
      biceps tendon: a comparison of 4 techniques.
AB  - HYPOTHESIS: It is unknown whether certain methods of distal biceps tendon repair
      lead to an increased propensity of impingement of the repaired tendon. The
      purpose of this study was to evaluate various repair techniques in a cadaveric
      model to determine the radioulnar space available for the repaired biceps
      tendons. METHODS: Nine matched pairs of quartered, fresh-frozen cadaveric arms
      were transected at the level of the humeral mid shaft and the distal radiocarpal
      joint. Distance measurements and the angular relation of the bicipital tuberosity
      were measured at 5 forearm pronation-supination positions. These measurements
      were taken under each of the following conditions: intact native biceps, resected
      native tendon, suture anchor fixation of the biceps, suspensory suture device
      fixation of the biceps, tendon repair using a tenodesis technique, and fixation
      of the tendon using a trough technique. RESULTS: There were no significant
      differences in radioulnar space available after biceps tendon repair with the
      forearm in a supinated position. However, when the forearm was in a neutral or
      pronated position, the suture anchor method consistently had the lowest biceps
      insertion-to-ulna distance (0.6 to 2.1 cm). All forearm positions, except full
      supination, showed significant differences in terms of radioulnar space available
      for the repaired biceps. DISCUSSION: This study shows that the space available
      for the biceps tendon decreases with forearm pronation after reconstruction for
      all repair techniques. It appears that using suture anchors to repair the biceps
      tendon may predispose the repaired tendon to impingement when compared with other
      fixation techniques.

PMID- 24862253
TI  - Leveraging the ambipolar transport in polymeric field-effect transistors via
      blending with liquid-phase exfoliated graphene.
AB  - Enhancement in the ambipolar behavior of field-effect transistors based on an n
      type polymer, P(NDI2OD-T2), is obtained by co-deposition with liquid-phase
      exfoliated graphene. This approach provides a prospective pathway for the
      application of graphene-based nanocomposites for logic circuits. 

PMID- 24862254
TI  - Impaired spatial learning and reduced adult hippocampal neurogenesis in histamine
      H1-receptor knockout mice.
AB  - The histamine H1-receptor (H1R) is expressed in wide parts of the brain including
      the hippocampus, which is involved in spatial learning and memory. Previous
      studies in H1R knockout (H1R-KO) mice revealed deficits in a variety of learning
      and memory tasks. It was also proposed that H1R activation is crucial for
      neuronal differentiation of neural progenitors. Therefore, the aim of this study
      was to investigate negatively reinforced spatial learning in the water-maze and
      to assess survival and neuronal differentiation of newborn cells in the adult
      hippocampus of H1R-KO mice. H1R-KO and wild-type (WT) mice were subjected to the
      following sequence of tests: (a) cued version, (b) place learning, (c) spatial
      probe, (d) long-term retention and (e) reversal learning. Furthermore hippocampal
      neurogenesis in terms of survival and differentiation was assessed in H1R-KO and
      WT mice. H1R-KO mice showed normal cued learning, but impaired place and reversal
      learning as well as impaired long-term retention performance. In addition, a
      marked reduction of newborn neurons in the hippocampus but no changes in
      differentiation of neural progenitors into neuronal and glial lineage was found
      in H1R-KO mice. Our data suggest that H1R deficiency in mice is associated with
      pronounced deficits in hippocampus-dependent spatial learning and memory.
      Furthermore, we herein provide first evidence that H1R deficiency in the mouse
      leads to a reduced neurogenesis. However, the exact mechanisms for the reduced
      number of cells in H1R-KO mice remain elusive and might be due to a reduced
      survival of newborn hippocampal neurons and/or a reduction in cell proliferation.

PMID- 24862251
TI  - Developmental process emerges from extended brain-body-behavior networks.
AB  - Studies of brain connectivity have focused on two modes of networks: structural
      networks describing neuroanatomy and the intrinsic and evoked dependencies of
      functional networks at rest and during tasks. Each mode constrains and shapes the
      other across multiple timescales and each also shows age-related changes. Here we
      argue that understanding how brains change across development requires
      understanding the interplay between behavior and brain networks: changing bodies
      and activities modify the statistics of inputs to the brain; these changing
      inputs mold brain networks; and these networks, in turn, promote further change
      in behavior and input. 

PMID- 24862252
TI  - Topographic organization in the brain: searching for general principles.
AB  - The neurons comprising many cortical areas have long been known to be arranged
      topographically such that nearby neurons have receptive fields at nearby
      locations in the world. Although this type of organization may be universal in
      primary sensory and motor cortex, in this review we demonstrate that associative
      cortical areas may not represent the external world in a complete and continuous
      fashion. After reviewing evidence for novel principles of topographic
      organization in macaque lateral intraparietal area (LIP) - one of the most
      studied associative areas in the parietal cortex - we explore the implications of
      these new principles for brain function. 

PMID- 24862255
TI  - Sodium valproate in migraine without aura and medication overuse headache: a
      randomized controlled trial.
AB  - OBJECTIVE: To assess the efficacy, safety and tolerability of sodium valproate
      (800mg/die) compared with placebo in medication-overuse headache patients with a
      history of migraine without aura. METHODS: This is a multicenter, randomized,
      double-blind, placebo-controlled study enrolled medication-overuse headache
      patients for a 3-month treatment period with sodium valproate (800mg/day) or
      placebo after a 6 day outpatient detoxification regimen, followed by a 3-month
      follow-up. Primary outcome was defined by the proportion of patients achieving
      >=50% reduction in the number of days with headache per month (responders) from
      the baseline to the last 4 weeks of the 3-month treatment. Multivariate logistic
      regression models were used on the primary endpoint, adjusting for age, sex,
      disease duration, comorbidity and surgery. The last-observation-carried-forward
      method was used to adjust for missing values. RESULTS: Nine sites enrolled 130
      patients and, after a 6-day detoxification phase, randomized 88 eligible
      patients. The 3-month responder rate was higher in the sodium valproate (45.0%)
      than in the placebo arm (23.8%) with an absolute difference of about 20%
      (p=0.0431). Sodium valproate had safety and tolerability profiles comparable to
      placebo. CONCLUSIONS: The present study supports the efficacy and safety of
      sodium valproate in the treatment of medication overuse headache with history of
      migraine after detoxification.

PMID- 24862256
TI  - 5-hydroxytryptamine- and dopamine-releasing effects of ring-substituted
      amphetamines on rat brain: a comparative study using in vivo microdialysis.
AB  - Using in vivo microdialysis, a comparative study was conducted to examine the
      effects of amphetamine-related compounds (methamphetamine, MAP; 3,4
      methylenedioxymethamphetamine, MDMA; p-methoxyamphetamine, PMA; p
      methoxymethamphetamine, PMMA; 4-methylthioamphetamine, 4-MTA; 3,4,5
      trimethoxyamphetamine, TMA; 2,5-dimethoxy-4-iodoamphetamine, DOI) on
      extracellular levels of serotonin (5-HT) and dopamine (DA). Dialysates were
      assayed using HPLC equipped with electrochemical detector following i.p.
      administration with each drug at a dose of 5 mg/kg. MAP was found to drastically
      and rapidly increase 5-HT and DA levels (870% and 1460%, respectively). PMA,
      PMMA, and 4-MTA slightly increased DA levels (150-290%) but remarkably increased
      5-HT levels (540-900%). In contrast, TMA and DOI caused no detectable changes in
      levels of both monoamines. We observed that the potent DA-releasing action of MAP
      was remarkably decreased by introduction of methoxy or methylthio group at the
      para position (MAP vs. PMMA or 4-MTA), but introduction of two additional
      adjacent methoxy groups into PMA totally abolished its 5-HT-/DA-releasing action
      (PMA vs. TMA). In addition, para-mono-substituted compounds inhibited both
      monoamine oxidase (MAO) enzymes more strongly than other compounds; PMA and 4-MTA
      exhibited submicromolar IC50 values for MAO-A. On the other hand, TMA scarcely
      affected the activity of both MAO enzymes as well as extracellular levels of 5-HT
      and DA. In this comparative study, MDMA, PMA, and 4-MTA functioned similar to
      PMMA, a typical empathogen; these findings therefore could be helpful in
      clarifying the psychopharmacological properties of amphetamine-related,
      empathogenic designer drugs.

PMID- 24862257
TI  - How antipsychotics impact the different dimensions of Schizophrenia: a test of
      competing hypotheses.
AB  - The clinical expression of schizophrenia is generally reported to be expressed by
      three to five different factors (i.e. positive, negative, disorganization,
      excitability, anxiety-depression symptoms). It is often claimed that
      antipsychotic medications are particularly helpful for positive symptoms, but not
      for the others, suggesting a differential efficacy for different aspects of the
      disorder. We formally tested this claim. Using Structural Equation Modeling in
      two large [1884 patients] clinical trials in schizophrenia, we compared the model
      of a common general effect of antipsychotics to models whereby the antipsychotics
      have multiple and differential effects on the different factors of the illness.
      We validated the generalizability of the model in further trials involving
      antipsychotics in chronic [1460 patients] and first-episode patients [1053
      patients]. Across different populations, different trials and different
      antipsychotics - the best-fitting model suggests that symptom response in
      schizophrenia is underpinned by a single general effect with secondary and minor
      lower-order effects on specific symptom domains. This single-factor model
      explained nearly 80% of the variance, was superior to the assumption of unique
      efficacy for specific domains; and replicated across antipsychotics and illness
      stages. Despite theoretical and pharmacological claims the differential efficacy
      of antipsychotics on the various dimensions of schizophrenia is not supported in
      the prevailing data. The implication of this finding for the measurement of
      treatment response and our understanding of the neurobiology of antipsychotic
      action, for clinical practice and for future drug development are discussed. 

PMID- 24862258
TI  - The metabolic alterations of cancer cells.
AB  - Cancer cells exhibit profound metabolic alterations, allowing them to fulfill the
      metabolic needs that come with increased proliferation and additional facets of
      malignancy. Such a metabolic transformation is orchestrated by the genetic
      changes that drive tumorigenesis, that is, the activation of oncogenes and/or the
      loss of oncosuppressor genes, and further shaped by environmental cues, such as
      oxygen concentration and nutrient availability. Understanding this metabolic
      rewiring is essential to elucidate the fundamental mechanisms of tumorigenesis as
      well as to find novel, therapeutically exploitable liabilities of malignant
      cells. Here, we describe key features of the metabolic transformation of cancer
      cells, which frequently include the switch to aerobic glycolysis, a profound
      mitochondrial reprogramming, and the deregulation of lipid metabolism,
      highlighting the notion that these pathways are not independent but rather
      cooperate to sustain proliferation. Finally, we hypothesize that only those
      genetic defects that effectively support anabolism are selected in the course of
      tumor progression, implying that cancer-associated mutations may undergo a
      metabolically convergent evolution. 

PMID- 24862260
TI  - Regulation of cancer metabolism by oncogenes and tumor suppressors.
AB  - Cell proliferation requires the coordination of multiple signaling pathways as
      well as the provision of metabolic substrates. Nutrients are required to generate
      such building blocks and their form of utilization differs to significant extents
      between malignant tissues and their nontransformed counterparts. Thus, oncogenes
      and tumor suppressor genes regulate the proliferation of cancer cells also by
      controlling their metabolism. Here, we discuss the central anabolic functions of
      the signaling pathways emanating from mammalian target of rapamycin, MYC, and
      hypoxia-inducible factor-1. Moreover, we analyze how oncogenic proteins like
      phosphoinositide-3-kinase, AKT, and RAS, tumor suppressors such as phosphatase
      and tensin homolog, retinoblastoma, and p53, as well as other factors associated
      with the proliferation or survival of cancer cells, such as NF-kappaB, regulate
      cellular metabolism. 

PMID- 24862261
TI  - Cross talk between cell death regulation and metabolism.
AB  - Accumulating evidence indicates that metabolism plays a critical role in the
      control of various cellular functions, including cell death. Thus, several
      mechanisms of programmed cell death have been shown to be controlled by metabolic
      cues. Since programmed cell death represents a fundamental process in various
      physiological and pathophysiological conditions, including oncogenesis, tumor
      progression, and resistance to therapy, the metabolic profile of cancer cells is
      expected to have a significant impact on all these phases of malignant
      transformation. Further insights into the signal transduction cascades that
      regulate different cell death pathways in response to metabolic fluctuations will
      likely result in the identification of potential targets for the development of
      novel therapeutic interventions. As the deregulation of cell metabolism as well
      as alterations in cell death pathways are involved in the pathogenesis of
      multiple human diseases other than cancer, this knowledge has a great
      translational potential in several areas of medicine. 

PMID- 24862263
TI  - Measurement of enolase activity in cell lysates.
AB  - Enolase (EC 4.2.1.11) is a cytosolic metalloenzyme responsible for the conversion
      of 2-phosphoglycerate into phosphoenolpyruvate, the second to last step in
      glycolysis. In mammals, enolase is encoded by three homologous genes. These gene
      products not only possess distinct biochemical and immunological properties but
      also show different tissue distribution. Besides its glycolytic function, alpha
      enolase plays a variety of roles in pathophysiological settings including
      oncogenesis, tumor progression, ischemia, and bacterial infection. The expression
      levels of alpha-enolase have been attributed diagnostic and prognostic value in a
      number of tumors. Furthermore, neuron-specific alpha-enolase is released into the
      cerebrospinal fluid as well as in the systemic circulation upon traumatic brain
      injury and ischemic episodes. Thus, the measurement of the enzymatic activity of
      enolase is relevant for diverse fields of investigation, including
      oncometabolism. Here, we described simple and rapid protocols to measure the
      activity of enolase in lysates from mammalian cells and tissues. 

PMID- 24862264
TI  - Extracellular flux analysis to monitor glycolytic rates and mitochondrial oxygen
      consumption.
AB  - Evidence accumulating over the past decade has linked alterations in bioenergetic
      metabolism to the pathogenesis of several diseases, including inflammatory
      conditions and cancer. However, the mutual relationship between the effector
      functions and the metabolism of immune cells has begun to emerge only recently.
      Similar to malignant cells, both innate and adaptive immune cells undergo a
      metabolic reprogramming that is required for effector functions, de facto
      underlying the elicitation of a robust immune response. These changes allow
      immune cells not only to rapidly respond to pathogens or (pre)malignant cells but
      also to adapt to changing microenvironmental conditions. Targeting the metabolic
      alterations of malignant cells has been the subject of an intense wave of
      investigation, resulting in the identification of promising therapeutic
      strategies. Since the inflammatory milieu and the tumor microenvironment are
      similar, the metabolism of immune cells and its regulation has recently come
      under renewed interest as a target for immunotherapy. Here, we describe different
      tools and techniques to study the bioenergetic metabolism of cultured cells,
      using immune cells as a model. Our methodological approach relies on an
      extracellular flux analyzer, an instrument that enables the real-time measurement
      of the two central pathways used by living cells to generate adenosine
      triphosphate: glycolysis and oxidative phosphorylation. This instrument and
      similar technological innovations have transformed the study of cellular
      metabolism, unveiling its profound impact on various immunologic and oncological
      disorders. 

PMID- 24862259
TI  - Autophagy and cancer metabolism.
AB  - The metabolism of malignant cells is profoundly altered in order to maintain
      their survival and proliferation in adverse microenvironmental conditions.
      Autophagy is an intracellular recycling process that maintains basal levels of
      metabolites and biosynthetic intermediates under starvation or other forms of
      stress, hence serving as an important mechanism for metabolic adaptation in
      cancer cells. Although it is widely acknowledged that autophagy sustains
      metabolism in neoplastic cells under duress, many questions remain with regard to
      the mutual relationship between autophagy and metabolism in cancer. Importantly,
      autophagy has often been described as a "double-edged sword" that can either
      impede or promote cancer initiation and progression. Here, we overview such a
      dual function of autophagy in tumorigenesis and our current understanding of the
      coordinated regulation of autophagy and cancer cell metabolism in the control of
      tumor growth, progression, and resistance to therapy. 

PMID- 24862262
TI  - Techniques to monitor glycolysis.
AB  - An increased flux through glycolysis supports the proliferation of cancer cells
      by providing additional energy in the form of ATP as well as glucose-derived
      metabolic intermediates for nucleotide, lipid, and protein biosynthesis. Thus,
      glycolysis and other metabolic pathways that control cell proliferation may
      represent valuable targets for therapeutic interventions and diagnostic
      procedures. In this context, the measurement of glucose uptake and lactate
      excretion by malignant cells may be useful to detect shifts in glucose
      catabolism, while determining the activity of rate-limiting glycolytic enzymes
      can provide insights into points of metabolic regulation. Moreover, metabolomic
      studies can be used to generate large, integrated datasets to track changes in
      carbon flux through glycolysis and its collateral anabolic pathways. As discussed
      here, these approaches can reveal and quantify the metabolic alterations that
      underlie malignant cell proliferation. 

PMID- 24862265
TI  - Conventional techniques to monitor mitochondrial oxygen consumption.
AB  - Following several key discoveries on hypoxia-inducible factors, we have observed
      an explosion of studies investigating how the hypoxic microenvironment provokes
      bioenergetic alterations. This is particularly relevant for cancer cells, as they
      are often exposed to hypoxic conditions in the course of tumor progression. Thus,
      interest in the measurement of oxygen consumption at the tissue, cell, or
      mitochondrion level has been revived. Here, we describe the basic principles of
      cellular respiration and survey some of the conventional methods for measuring O2
      consumption in intact or permeabilized cells. 

PMID- 24862266
TI  - Use of safranin for the assessment of mitochondrial membrane potential by high
      resolution respirometry and fluorometry.
AB  - The mitochondrial transmembrane potential (Deltapsimt or mtMP) is directly
      influenced by oxidative phosphorylation (OXPHOS). The exact nature of the
      interactions between respiration (flux) and mtMP (force) under various
      physiological and pathological conditions remains unclear, partially due to
      methodological limitations. Here, we describe a combination of high-resolution
      respirometry and fluorometry based on the OROBOROS Oxygraph-2k and the widely
      applied mtMP indicator safranin. The analysis of OXPHOS in mouse brain
      homogenates revealed that, at commonly applied concentrations, safranin inhibits
      Complex I-driven OXPHOS capacity, primarily targeting the phosphorylation system,
      but has no effects on LEAK respiration. Conversely, Complex II-driven OXPHOS
      capacity was inhibited by <20% by safranin concentrations normally used for mtMP
      monitoring. The mtMP was higher in the LEAK state without adenylates than at
      identical LEAK respiration after ADP stimulation and Complex V inhibition with
      oligomycin. The maximal electron transfer system (ETS) capacity was reached in
      uncoupler titrations before the mtMP fully collapsed, whereas respiration was
      inhibited at increasing uncoupler concentrations, resulting in the progressive
      reduction of mtMP. In a pharmacologically induced state of Complex II
      dysfunction, mtMP was rather insensitive to the inhibition of OXPHOS to 50% of
      its normal capacity, but robustly responded to inhibitors when respiration was
      limited by substrate depletion. The optimal concentration of uncoupler supporting
      maximal ETS capacity varied as a function of pharmacological intervention. Taken
      together, the combined measurement of respiration and mtMP greatly enhances the
      informative potential of OXPHOS studies. The respirometric validation of
      inhibitory and uncoupling effects is mandatory for any fluorophore employed to
      assess mtMP in any respiratory state, tissue type, and pathophysiological
      condition. The methodological issues analyzed herein are relevant for the study
      of mitochondrial respiration in a wide variety of setting, including cancer cell
      metabolism. 

PMID- 24862267
TI  - Kinetic analysis of local oxygenation and respiratory responses of mammalian
      cells using intracellular oxygen-sensitive probes and time-resolved fluorometry.
AB  - The cell-penetrating O2-sensing probes based on phosphorescent Pt-porphyrins
      provide a means to accurately measure O2 within cultured cells in a contact-less
      fashion. Via this approach, in situ oxygenation and respiratory responses can be
      monitored in real time on large number of cellular samples seeded in standard
      microtiter plates, by means of a commercial time-resolved fluorescence reader.
      Using neuronal PC12 cells as a model, here we describe the general strategy
      behind the use of phosphorescent Pt-porphyrins to measure O2 within cultured
      cells as well as detailed protocols to implement this experimental approach,
      including cell preparation and probe loading, instrument and plate setup, system
      calibration, and data processing. Two main protocols are presented: (1) a basic
      setup and optimization for the measurement of intracellular O2 under ambient O2
      concentration; (2) the calibration of the system required to perform measurements
      under low O2 concentrations (hypoxia). A case study on the effects of bafilomycin
      A1 on PC12 cell function is included, illustrating how these methods can be
      combined with conventional bioenergetic markers to delineate how chemical and/or
      physical stimuli affect the metabolism of normal and malignant cells. 

PMID- 24862268
TI  - Cell-based measurements of mitochondrial function in human subjects.
AB  - There is growing evidence in the basic science field that aberrant metabolism
      plays an important role in tumorigenesis. Therefore, it is imperative to perform
      investigations in human subjects to determine (1) whether the metabolic
      observations made in model systems are applicable to humans; and (2) if indeed
      applicable, whether the metabolic alterations are clinically significant for
      cancer development. As an initial step, here we describe methods for measuring
      the mitochondrial metabolism of blood lymphocytes and skeletal muscle myoblasts
      that can be obtained from human subjects. 

PMID- 24862269
TI  - Use of chemical probes to detect mitochondrial ROS by flow cytometry and
      spectrofluorometry.
AB  - Aerobic respiration is a major source of energy in eukaryotic cells. In this
      setting, ATP production by the mitochondrial respiratory chain relies on the
      availability of NADH and FADH2 to donate protons and electrons. The flux of
      electrons down the electron transport chain, based on a series of oxidation
      reduction reactions, releases energy that allow for the transport of H(+) ions
      across the inner mitochondrial membrane. The resulting proton-motive force is
      employed to drive ATP synthesis, while the final acceptor of the electrons
      flowing through the respiratory chain if molecular oxygen. A side effect of this
      process is the generation of reactive oxygen species (ROS). While mitochondrial
      ROS (mtROS) production has been linked to many pathological conditions (i.e.,
      aging and tumorigenesis), recent evidence suggests that multiple cells, including
      malignant cells, employ these by-products of energy production as signals to
      control various cellular processes. Here, we describe protocols to use chemical
      probes for measuring mtROS production in intact cells by flow cytometry and
      spectrofluorometry. 

PMID- 24862270
TI  - Methods to monitor ROS production by fluorescence microscopy and fluorometry.
AB  - Mitochondria are considered one of the main sources of reactive oxygen species
      (ROS). The overgeneration of ROS can evoke an intracellular state of oxidative
      stress, leading to permanent cell damage. Thus, the intracellular accumulation of
      ROS may not only disrupt the functions of specific tissues and organs but also
      lead to the premature death of the entire organism. Less severe increases in ROS
      levels may lead to the nonlethal oxidation of fundamental cellular components,
      such as proteins, phospholipids, and DNA, hence exerting a mutagenic effect that
      promotes oncogenesis and tumor progression. Here, we describe the use of chemical
      probes for the rapid detection of ROS in intact and permeabilized adherent cells
      by fluorescence microscopy and fluorometry. Moreover, after discussing the
      limitations described in the literature for the fluorescent probes presented
      herein, we recommend methods to assess the production of specific ROS in various
      fields of investigation, including the study of oncometabolism. 

PMID- 24862271
TI  - Genetically encoded redox sensors.
AB  - Endogenous redox sensors detect fluctuations in the intracellular redox
      equilibrium and are critical for the maintenance of homeostasis. Such systems
      have been exploited to engineer genetically encoded redox sensors to detect
      dynamic oxidative changes within a cellular environment. Most genetically encoded
      redox sensors detect reactive oxygen species (ROS) such as superoxide anion,
      hydrogen peroxide and hydroxyl radical. Technical hurdles including the limited
      temporal and spatial resolution as well as tissue heterogeneity have complicated
      the realization of the full potential of genetically encoded redox sensors in
      animals until recently. Alterations in the concentration and subcellular
      localization of ROS are integral to numerous disorders, including
      neurodegenerative diseases and cancer. Thus, genetically encoded redox sensors
      are useful for the study of the pathogenesis and progression of multiple
      diseases. Moreover, the ultimate generation of genetically encoded redox sensors
      provides substantial advantages over conventional methods such as ROS-sensitive
      fluorescent probes. Here, we review examples of genetically encoded redox
      sensors, present their application to various fields of biomedical investigation,
      including the study of oncometabolism, discuss their drawbacks and explore future
      developments. 

PMID- 24862272
TI  - Use of genetically encoded sensors to monitor cytosolic ATP/ADP ratio in living
      cells.
AB  - ATP is not only recognized as the universal energy "currency" in most cells but
      also plays a less well-known role as an intracellular and extracellular
      messenger. Here, we review novel approaches for measuring free ATP (or ATP/ADP
      ratios) in living mammalian cells by using genetically encoded sensors. We also
      discuss the key technical aspects of routine real-time ATP/ADP monitoring using
      as a model one of the last-generation fluorescent probes, a fusion protein
      commonly known as "Perceval." Finally, we present detailed guidelines for the
      simultaneous measurement of cytosolic ATP/ADP ratios and Ca(2+) concentrations
      alongside electrical parameters in individual pancreatic beta cells, in which
      energy metabolism is tightly linked to plasma membrane excitability to control
      the secretion of insulin. With appropriate variations, this approach can be
      adapted to the study of cytosolic ATP/ADP ratios and Ca(2+) concentrations in
      malignant cells, two important aspects of oncometabolism. 

PMID- 24862273
TI  - Methods to monitor and compare mitochondrial and glycolytic ATP production.
AB  - ATP is commonly considered as the main energy unit of the cell and participates
      in a variety of cellular processes. Thus, intracellular ATP concentrations
      rapidly vary in response to a wide variety of stimuli, including nutrients,
      hormones, cytotoxic agents, and hypoxia. Such alterations not necessarily affect
      cytosolic and mitochondrial ATP to similar extents. From an oncological
      perspective, this is particularly relevant in the course of tumor progression as
      well as in the response of cancer cells to therapy. In normal cells,
      mitochondrial oxidative phosphorylation (OXPHOS) is the predominant source of
      ATP. Conversely, many cancer cells exhibit an increased flux through glycolysis
      irrespective of oxygen tension. Assessing the relative contribution of glycolysis
      and OXPHOS to intracellular ATP production is fundamental not only for obtaining
      further insights into the peculiarities and complexities of oncometabolism but
      also for developing therapeutic and diagnostic tools. Several techniques have
      been developed to measure intracellular ATP levels including enzymatic methods
      based on hexokinase, glucose-6-phosphate dehydrogenase, and firefly luciferase.
      Here, we summarize conventional methods for measuring intracellular ATP levels
      and we provide a detailed protocol based on cytosol- and mitochondrion-targeted
      variants of firefly luciferase to determine the relative contribution of
      glycolysis and OXPHOS to ATP synthesis. 

PMID- 24862274
TI  - Measurement of ADP-ATP exchange in relation to mitochondrial transmembrane
      potential and oxygen consumption.
AB  - We have previously described a fluorometric method to measure ADP-ATP exchange
      rates in mitochondria of permeabilized cells, in which several enzymes that
      consume substantial amounts of ATP and other competing reactions interconverting
      adenine nucleotides are present. This method relies on recording changes in free
      extramitochondrial Mg(2+) with the Mg(2+)-sensitive fluorescent indicator
      Magnesium Green (MgGr)TM, exploiting the differential affinity of ADP and ATP for
      Mg(2+). In particular, cells are permeabilized with digitonin in the presence of
      BeF3(-) and Na3VO4, inhibiting all ATP- and ADP-utilizing reactions but
      mitochondrial exchange of ATP with ADP catalyzed by the adenine nucleotide
      translocase. The rate of ATP appearing in the medium upon the addition of ADP to
      energized mitochondria is then calculated from the rate of change in free
      extramitochondrial Mg(2+) using standard binding equations. Here, we describe a
      variant of this method involving an improved calibration step. This step
      minimizes errors that may be introduced during the conversion of the MgGrTM
      signal into free extramitochondrial [Mg(2+)] and ATP. Furthermore, we describe an
      approach for combining this methodology with the measurement of mitochondrial
      membrane potential and oxygen consumption in the same sample. The method
      described herein is useful for the study of malignant cells, which are known to
      thrive in hypoxic environments and to harbor mitochondria with profound
      functional alterations.

PMID- 24862275
TI  - Real-time assessment of the metabolic profile of living cells with genetically
      encoded NADH sensors.
AB  - Redox metabolism plays a critical role in multiple pathophysiological settings,
      including oncogenesis and tumor progression. Until recently, however, our
      knowledge of key redox processes in living systems was limited by the lack of an
      adequate methodology to monitor redox potential. Nicotinamide adenine
      dinucleotide, in its reduced (NADH) and oxidized (NAD(+)) forms, is perhaps the
      most important small molecule in the redox metabolism of mammalian cells. We have
      previously developed a series of genetically encoded fluorescent sensors allowing
      for the quantification of intracellular NADH. Here, we present experimental
      components and considerations that are required to perform a standardized
      quantification of intracellular NADH based on these probes. Moreover, we present
      the initial calibration experiments necessary to obtain reliable data from this
      approach, we detail a protocol to measure intracellular NADH levels in steady
      state kinetic experiments, and we provide consideration on the processing of
      data. Among various applications, this technique is suitable for the study of
      redox alterations in malignant cells. 

PMID- 24862276
TI  - 13C isotope-assisted methods for quantifying glutamine metabolism in cancer
      cells.
AB  - Glutamine has recently emerged as a key substrate to support cancer cell
      proliferation, and the quantification of its metabolic flux is essential to
      understand the mechanisms by which this amino acid participates in the metabolic
      rewiring that sustains the survival and growth of neoplastic cells. Glutamine
      metabolism involves two major routes, glutaminolysis and reductive carboxylation,
      both of which begin with the deamination of glutamine to glutamate and the
      conversion of glutamate into alpha-ketoglutarate. In glutaminolysis, alpha
      ketoglutarate is oxidized via the tricarboxylic acid cycle and decarboxylated to
      pyruvate. In reductive carboxylation, alpha-ketoglutarate is reductively
      converted into isocitrate, which is isomerized to citrate to supply acetyl-CoA
      for de novo lipogenesis. Here, we describe methods to quantify the metabolic flux
      of glutamine through these two routes, as well as the contribution of glutamine
      to lipid synthesis. Examples of how these methods can be applied to study
      metabolic pathways of oncological relevance are provided. 

PMID- 24862277
TI  - Measurement of fatty acid oxidation rates in animal tissues and cell lines.
AB  - While much oncological research has focused on metabolic shifts in glucose and
      amino acid oxidation, recent evidence suggests that fatty acid oxidation (FAO)
      may also play an important role in the metabolic reprogramming of cancer cells.
      Here, we present a simple method for measuring FAO rates using radiolabeled
      palmitate, common laboratory reagents, and standard supplies. This protocol is
      broadly applicable for measuring FAO rates in cultured cancer cells as well as in
      both malignant and nontransformed animal tissues. 

PMID- 24862278
TI  - Methods to assess lipid accumulation in cancer cells.
AB  - Oncogenesis and tumor progression are associated with significant alterations in
      cellular metabolism. One metabolic pathway that is commonly deregulated in
      malignant cells is de novo lipogenesis. Lipogenesis is indeed highly upregulated
      in several types of cancer, a phenomenon that is linked to tumor progression and
      poor prognosis. Steroid hormones play an essential role in the growth of a
      variety of cancers and have been shown to increase the expression and activity of
      several lipogenic factors, including fatty acid synthase and sterol regulatory
      element-binding proteins. Such an altered gene expression profile promotes lipid
      biogenesis and may result in the accumulation of neutral lipids, which become
      visible as cytoplasmic lipid droplets. By using breast and prostate cancer cells
      exposed to steroid hormones as a model, here we describe methods for the direct
      qualitative and quantitative assessment of neutral lipid accumulation in
      malignant cells. 

PMID- 24862279
TI  - Analysis of hypoxia-induced metabolic reprogramming.
AB  - Hypoxia is a common finding in advanced human tumors and is often associated with
      metastatic dissemination and poor prognosis. Cancer cells adapt to hypoxia by
      utilizing physiological adaptation pathways that promote a switch from oxidative
      to glycolytic metabolism. This promotes the conversion of glucose into lactate
      while limiting its transformation into acetyl coenzyme A (acetyl-CoA). The uptake
      of glucose and the glycolytic flux are increased under hypoxic conditions, mostly
      owing to the upregulation of genes encoding glucose transporters and glycolytic
      enzymes, a process that depends on hypoxia-inducible factor 1 (HIF-1). The
      reduced delivery of acetyl-CoA to the tricarboxylic acid cycle leads to a switch
      from glucose to glutamine as the major substrate for fatty acid synthesis in
      hypoxic cells. In addition, hypoxia induces (1) the HIF-1-dependent expression of
      BCL2/adenovirus E1B 19-kDa interacting protein 3 (BNIP3) and BNIP3-like (BNIP3L),
      which trigger mitochondrial autophagy, thereby decreasing the oxidative
      metabolism of both fatty acids and glucose, and (2) the expression of the sodium
      hydrogen exchanger NHE1, which maintains an alkaline intracellular pH. Here, we
      present a compendium of methods to study hypoxia-induced metabolic alterations. 

PMID- 24862280
TI  - Preface: oncometabolism: a new field of research with profound therapeutic
      implications.

PMID- 24862281
TI  - Systematic exploration of ubiquitin sequence, E1 activation efficiency, and
      experimental fitness in yeast.
AB  - The complexity of biological interaction networks poses a challenge to
      understanding the function of individual connections in the overall network. To
      address this challenge, we developed a high-throughput reverse engineering
      strategy to analyze how thousands of specific perturbations (encompassing all
      point mutations in a central gene) impact both a specific edge (interaction to a
      directly connected node) and an overall network function. We analyzed the effects
      of ubiquitin mutations on activation by the E1 enzyme and compared these to
      effects on yeast growth rate. Using this approach, we delineated ubiquitin
      mutations that selectively impacted the ubiquitin-E1 edge. We find that the
      elasticity function relating the efficiency of ubiquitin-E1 interaction to growth
      rate is non-linear and that a greater than 50-fold decrease in E1 activation
      efficiency is required to reduce growth rate by 2-fold. Despite the robustness of
      fitness to decreases in E1 activation efficiency, the effects of most ubiquitin
      mutations on E1 activation paralleled the effects on growth rate. Our
      observations indicate that most ubiquitin mutations that disrupt E1 activation
      also disrupt other functions. The structurally characterized ubiquitin-E1
      interface encompasses the interfaces of ubiquitin with most other known binding
      partners, and we propose that this enables E1 in wild-type cells to selectively
      activate ubiquitin protein molecules capable of binding to other partners from
      the cytoplasmic pool of ubiquitin protein that will include molecules with
      chemical damage and/or errors from transcription and translation. 

PMID- 24862282
TI  - Glycan specificity of the Vibrio vulnificus hemolysin lectin outlines
      evolutionary history of membrane targeting by a toxin family.
AB  - Pore-forming toxins (PFTs) are a class of pathogen-secreted molecules that
      oligomerize to form transmembrane channels in cellular membranes. Determining the
      mechanism for how PFTs bind membranes is important in understanding their role in
      disease and for developing possible ways to block their action. Vibrio
      vulnificus, an aquatic pathogen responsible for severe food poisoning and
      septicemia in humans, secretes a PFT called V. vulnificus hemolysin (VVH), which
      contains a single C-terminal targeting domain predicted to resemble a beta
      trefoil lectin fold. In order to understand the selectivity of the lectin for
      glycan motifs, we expressed the isolated VVH beta-trefoil domain and used glycan
      chip screening to identify that VVH displays a preference for terminal galactosyl
      groups including N-acetyl-d-galactosamine and N-acetyl-d-lactosamine. The X-ray
      crystal structure of the VVH lectin domain solved to 2.0A resolution reveals a
      heptameric ring arrangement similar to the oligomeric form of the related, but
      inactive, lectin from Vibrio cholerae cytolysin. Structures bound to glycerol, N
      acetyl-d-galactosamine, and N-acetyl-d-lactosamine outline a common and versatile
      mode of recognition allowing VVH to target a wide variety of cell-surface
      ligands. Sequence analysis in light of our structural and functional data
      suggests that VVH may represent an earlier step in the evolution of Vibrio PFTs.

PMID- 24862283
TI  - Binding of ArgTX-636 in the NMDA receptor ion channel.
AB  - The N-methyl-d-aspartate receptors (NMDARs) constitute an important class of
      ligand-gated cation channels that are involved in the majority of excitatory
      neurotransmission in the human brain. Compounds that bind in the NMDAR ion
      channel and act as blockers are use- and voltage-dependent inhibitors of NMDAR
      activity and have therapeutic potential for treatment of a variety of brain
      diseases or as pharmacological tools for studies of the neurobiological role of
      NMDARs. We have performed a kinetic analysis of the blocking mechanism of the
      prototypical polyamine toxin NMDAR ion channel blocker argiotoxin-636 (ArgTX-636)
      at recombinant GluN1/2A receptors to provide detailed information on the
      mechanism of block. The predicted binding site of ArgTX-636 is in the pore region
      of the NMDAR ion channel formed by residues in the transmembrane M3 and the M2
      pore-loop segments of the GluN1 and GluN2A subunits. To assess the predicted
      binding mode in further detail, we performed an alanine- and glycine-scanning
      mutational analysis of this pore-loop segment to systematically probe the role of
      pore-lining M2 residues in GluN1 and GluN2A in the channel block by ArgTX-636.
      Comparison of M2 positions in GluN1 and GluN2A where mutation influences ArgTX
      636 potency suggests differential contribution of the M2-loops of GluN1 and
      GluN2A to binding of ArgTX-636. The results of the mutational analysis are highly
      relevant for the future structure-based development of argiotoxin-derived NMDAR
      channel blockers.

PMID- 24862285
TI  - Assembly of Helicobacter pylori initiation complex is determined by sequence
      specific and topology-sensitive DnaA-oriC interactions.
AB  - In bacteria, chromosome replication is initiated by binding of the DnaA initiator
      protein to DnaA boxes located in the origin of chromosomal replication (oriC).
      This leads to DNA helix opening within the DNA-unwinding element. Helicobacter
      pylori oriC, the first bipartite origin identified in Gram-negative bacteria,
      contains two subregions, oriC1 and oriC2, flanking the dnaA gene. The DNA
      unwinding element region is localized in the oriC2 subregion downstream of dnaA.
      Surprisingly, oriC2-DnaA interactions were shown to depend on DNA topology, which
      is unusual in bacteria but is similar to initiator-origin interactions observed
      in higher organisms. In this work, we identified three DnaA boxes in the oriC2
      subregion, two of which were bound only as supercoiled DNA. We found that all
      three DnaA boxes play important roles in orisome assembly and subsequent DNA
      unwinding, but different functions can be assigned to individual boxes. This
      suggests that the H. pylori oriC may be functionally divided, similar to what was
      described recently for Escherichia coli oriC. On the basis of these results, we
      propose a model of initiation complex formation in H. pylori. 

PMID- 24862286
TI  - Characterisation of bacterioplankton communities in the meltwater ponds of
      Bratina Island, Victoria Land, Antarctica.
AB  - A unique collection of Antarctic aquatic environments (meltwater ponds) lies in
      close proximity on the rock and sediment-covered undulating surface of the
      McMurdo Ice Shelf, near Bratina Island (Victoria Land, Antarctica). During the
      2009-10 mid-austral summer, sets of discrete water samples were collected across
      the vertical geochemical gradients of five meltwater ponds (Egg, P70E, Legin,
      Salt and Orange) for geochemical and microbial community structure analysis.
      Bacterial DNA fingerprints (using Automated Ribosomal Intergenic Spacer Analysis)
      statistically clustered communities within ponds based on anosim (R = 0.766, P =
      0.001); however, one highly stratified pond (Egg) had two distinct depth-related
      bacterial communities (R = 0.975, P = 0.008). 454 pyrosequencing at three depths
      within Egg also identified phylum level shifts and increased diversity with
      depth, Bacteroidetes being the dominant phyla in the surface sample and
      Proteobacteria being dominant in the bottom two depths. best analysis, which
      attempts to link community structure and the geochemistry of a pond, identified
      conductivity and pH individually, and to a lesser extent Ag(109) , NO2 and V(51)
      as dominant influences to the microbial community structure in these ponds.
      Increasing abundances of major halo-tolerant OTUs across the strong conductivity
      gradient reinforce it as the primary driver of community structure in this study.

PMID- 24862284
TI  - Competition as a way of life for H(+)-coupled antiporters.
AB  - Antiporters are ubiquitous membrane proteins that catalyze obligatory exchange
      between two or more substrates across a membrane in opposite directions. Some
      utilize proton electrochemical gradients generated by primary pumps by coupling
      the downhill movement of one or more protons to the movement of a substrate.
      Since the direction of the proton gradient usually favors proton movement toward
      the cytoplasm, their function results in removal of substrates other than protons
      from the cytoplasm, either into acidic intracellular compartments or out to the
      medium. H(+)-coupled antiporters play central roles in living organisms, for
      example, storage of neurotransmitter and other small molecules, resistance to
      antibiotics, homeostasis of ionic content and more. Biochemical and structural
      data support a general mechanism for H(+)-coupled antiporters whereby the
      substrate and the protons cannot bind simultaneously to the protein. In several
      cases, it was shown that the binding sites overlap, and therefore, there is a
      direct competition between the protons and the substrate. In others, the
      "competition" seems to be indirect and it is most likely achieved by allosteric
      mechanisms. The pKa of one or more carboxyls in the protein must be tuned
      appropriately in order to ensure the feasibility of such a mechanism. In this
      review, I discuss in detail the case of EmrE, a multidrug transporter from
      Escherichia coli and evaluate the information available for other H(+)-coupled
      antiporters. 

PMID- 24862287
TI  - Spinel-type lithium cobalt oxide as a bifunctional electrocatalyst for the oxygen
      evolution and oxygen reduction reactions.
AB  - Development of efficient, affordable electrocatalysts for the oxygen evolution
      reaction and the oxygen reduction reaction is critical for rechargeable metal-air
      batteries. Here we present lithium cobalt oxide, synthesized at 400  degrees C
      (designated as LT-LiCoO2) that adopts a lithiated spinel structure, as an
      inexpensive, efficient electrocatalyst for the oxygen evolution reaction. The
      catalytic activity of LT-LiCoO2 is higher than that of both spinel cobalt oxide
      and layered lithium cobalt oxide synthesized at 800  degrees C (designated as HT
      LiCoO2) for the oxygen evolution reaction. Although LT-LiCoO2 exhibits poor
      activity for the oxygen reduction reaction, the chemically delithiated LT-Li1
      xCoO2 samples exhibit a combination of high oxygen reduction reaction and oxygen
      evolution reaction activities, making the spinel-type LT-Li0,5CoO2 a potential
      bifunctional electrocatalyst for rechargeable metal-air batteries. The high
      activities of these delithiated compositions are attributed to the Co4O4 cubane
      subunits and a pinning of the Co(3+/4+):3d energy with the top of the O(2-):2p
      band. 

PMID- 24862288
TI  - Nanoparticulate zinc oxide as a coating material for orthopedic and dental
      implants.
AB  - Orthopedic and dental implants are prone to infection. In this study, we describe
      a novel system using zinc oxide nanoparticles (nZnO) as a coating material to
      inhibit bacterial adhesion and promote osteoblast growth. Electrohydrodynamic
      atomisation (EHDA) was employed to deposit mixtures of nZnO and
      nanohydroxyapatite (nHA) onto the surface of glass substrates. Nano-coated
      substrates were exposed to Staphylococcus aureus suspended in buffered saline or
      bovine serum to determine antimicrobial activity. Our results indicate that 100%
      nZnO and 75% nZnO/25% nHA composite-coated substrates have significant
      antimicrobial activity. Furthermore, osteoblast function was explored by exposing
      cells to nZnO. UMR-106 cells exposed to nZnO supernatants showed minimal
      toxicity. Similarly, MG-63 cells cultured on nZnO substrates did not show release
      of TNF-alpha and IL-6 cytokines. These results were reinforced by both
      proliferation and differentiation studies which revealed that a substrate coated
      with exclusively nZnO is more efficient than composite surface coatings. Finally,
      electron and light microscopy, together with immunofluorescence staining,
      revealed that all cell types tested, including human mesenchymal cell (hMSC),
      were able to maintain normal cell morphology when adhered onto the surface of the
      nano-coated substrates. Collectively, these findings indicate that nZnO can, on
      its own, provide an optimal coating for future bone implants that are both
      antimicrobial and biocompatible.

PMID- 24862289
TI  - Population pharmacokinetic analysis of ciprofloxacin in the elderly patients with
      lower respiratory tract infections.
AB  - The aims of the study were to develop a population pharmacokinetic model of
      ciprofloxacin (CPX) in the elderly patients and to examine the impact of patient
      dependent variables on pharmacokinetic parameter values of this drug. The study
      was conducted in a group of 44 patients at the age of 44-96years, hospitalized
      due to pneumonia lobaris or bronchopneumonia. Patients received CPX at a dose of
      200mg every 12h as a constant rate infusion over 0.5h. Concentrations of CPX in
      serum were measured by HPLC with UV detection. Population pharmacokinetic
      analysis revealed that CPX concentration versus time data were best described by
      a one-compartment model. The mean values of volume of distribution and clearance
      of CPX in the patients above 65years of age were 78.41+/-13.17L and 18.39+/
      4.15L/h, respectively. The creatinine clearance influenced CPX clearance
      according to the equation: CLCPX (L/h)=8.0+0.21.CLCr, while the volume of
      distribution of CPX was dependent on the body weight of the patient as follows:
      VdCPX (L)=22.72+0.86.WT. In summary, the developed population model can be used
      to assess the pharmacokinetic parameters of CPX in the elderly patients and to
      select on the basis of these parameters and MIC values an optimal dosage regimen
      of this drug. 

PMID- 24862290
TI  - Molecular evidence of osteoblast dysfunction in elderly men with osteoporotic hip
      fractures.
AB  - Osteoporosis is extremely frequent in post-menopausal women; nevertheless,
      osteoporosis in men is also a severe and frequently occurring but often
      underestimated disease. Increasing evidence links bone loss in male idiopathic
      osteoporosis and age related osteoporosis to osteoblast dysfunction rather than
      increased osteoclast activity as seen in postmenopausal osteoporosis. The aim of
      this study was to investigate gene expression of osteoblast related genes and of
      bone architecture in bone samples derived from elderly osteoporotic men with hip
      fractures (OP) in comparison to bone samples from age matched men with
      osteoarthritis of the hip (OA). Femoral heads and adjacent neck tissue were
      collected from 12 men with low-trauma hip fractures and consecutive surgical hip
      replacement. Bone samples of age matched patients undergoing hip replacement due
      to osteoarthritis served as controls. One half of the bone samples was subjected
      to RNA extraction, reverse transcription, and real-time polymerase chain
      reactions. The second half of the bone samples was analyzed by static
      histomorphometry. From each half samples from four different regions, the central
      and subcortical region of the femoral head and neck, were analyzed. OP patients
      displayed a significantly decreased RUNX2, Osterix and SOST expression compared
      to OA patients. Major microstructural changes in OP bone were seen in the
      subcortical region of the neck and were characterized by a significant decrease
      of bone volume, and a significant increase of trabecular separation. In
      conclusion, decreased local gene expression of RUNX2 and Osterix in men with hip
      fractures strongly supports the concept of osteoblast dysfunction in male
      osteoporosis. Major microstructural changes in the trabecular structure
      associated with osteoporotic hip fractures in men are localized in the
      subcortical region of the femoral neck. 

PMID- 24862291
TI  - Astrocyte-dependent protective effect of quetiapine on GABAergic neuron is
      associated with the prevention of anxiety-like behaviors in aging mice after long
      term treatment.
AB  - Previous studies have demonstrated that quetiapine (QTP) may have neuroprotective
      properties; however, the underlying mechanisms have not been fully elucidated. In
      this study, we identified a novel mechanism by which QTP increased the synthesis
      of ATP in astrocytes and protected GABAergic neurons from aging-induced death. In
      12-month-old mice, QTP significantly improved cell number of GABAegic neurons in
      the cortex and ameliorated anxiety-like behaviors compared to control group.
      Complimentary in vitro studies showed that QTP had no direct effect on the
      survival of aging GABAergic neurons in culture. Astrocyte-conditioned medium
      (ACM) pretreated with QTP (ACMQTP) for 24 h effectively protected GABAergic
      neurons against aging-induced spontaneous cell death. It was also found that QTP
      boosted the synthesis of ATP from cultured astrocytes after 24 h of treatment,
      which might be responsible for the protective effects on neurons. Consistent with
      the above findings, a Rhodamine 123 test showed that ACMQTP, not QTP itself, was
      able to prevent the decrease in mitochondrial membrane potential in the aging
      neurons. For the first time, our study has provided evidence that astrocytes may
      be the conduit through which QTP is able to exert its neuroprotective effects on
      GABAergic neurons. The neuroprotective properties of quetiapine (QTP) have not
      been fully understood. Here, we identify a novel mechanism by which QTP increases
      the synthesis of ATP in astrocytes and protects GABAergic neurons from aging
      induced death in a primary cell culture model. In 12-month-old mice, QTP
      significantly improves cell number of GABAegic neurons and ameliorates anxiety
      like behaviors. Our study indicates that astrocytes may be the conduit through
      which QTP exerts its neuroprotective effects on GABAergic neurons.

PMID- 24862292
TI  - Straightforward synthesis of the Bronsted acid hfipOSO3H and its application for
      the synthesis of protic ionic liquids.
AB  - The easily accessible hexafluoroisopropoxysulfuric acid (1, hfipOSO3H; hfip =
      C(H)(CF3)2) was synthesized by the reaction of hexafluoroisopropanol and
      chlorosulfonic acid on the kilogram scale and isolated in 98 % yield. The
      calculated gas-phase acidity (GA) value of 1 is 58 kJ mol(-1) lower in DeltaG
      degrees  than that of sulfuric acid (GA value determined by a CCSD(T)-MP2
      compound method). Considering the gas-phase dissociation constant as a measure
      for the intrinsic molecular acid strength, a hfipOSO3H molecule is more than ten
      orders of magnitude more acidic than a H2SO4 molecule. The acid is a liquid at
      room temperature, distillable at reduced pressure, stable for more than one year
      in a closed vessel, reactive towards common solvents, and decomposes above 180 
      degrees C. It is a versatile compound for further applications, such as the
      synthesis of ammonium- and imidazolium-based air- and moisture-stable protic
      ionic liquids (pILs). Among the six synthesized ionic compounds, five are pILs
      with melting points below 100  degrees C and three of them are liquids at nearly
      room temperature. The conductivities and viscosities of two representative ILs
      were investigated in terms of Walden plots, and the pILs were found to be little
      associated ILs, comparable to conventional aprotic ILs.

PMID- 24862293
TI  - Maternal sepsis incidence, aetiology and outcome for mother and fetus: a
      prospective study.
AB  - OBJECTIVE: To determine the incidence of maternal bacteraemia during pregnancy
      and for 6 weeks postpartum, describe the gestation/stage at which sepsis occurs,
      the causative microorganisms, antibiotic resistance and review maternal, fetal
      and neonatal outcome. DESIGN: Prospective review. SETTING: Two tertiary referral,
      maternity hospitals in Dublin, Ireland. POPULATION: During 2005-2012 inclusive,
      150 043 pregnant women attended and 24.4% of infants born in Ireland were
      delivered at the hospitals. METHODS: Demographic, clinical, microbiological and
      outcome data was collected from women with sepsis and compared with controls.
      MAIN OUTCOME MEASURES: Incidence, bacterial aetiology, gestation/stage at
      delivery, mode of delivery, antibiotic resistance, admission to augmented care,
      maternal, fetal and neonatal outcome. RESULTS: The sepsis rate was 1.81 per 1000
      pregnant women. Escherichia coli was the predominant pathogen, followed by Group
      B Streptococcus. Sepsis was more frequent among nulliparous women (odds ratio
      [OR] 1.39; 95% confidence interval [CI] 1.07-1.79) and multiple births (OR 2.04;
      95% CI 0.98-4.08). Seventeen percent of sepsis episodes occurred antenatally, 36%
      intrapartum and 47% postpartum. The source of infection was the genital tract in
      61% (95% CI 55.1-66.6) of patients and the urinary tract in 25% (95% CI 20.2
      30.5). Sepsis was associated with preterm delivery (OR 2.81; 95% CI 1.99-3.96)
      and a high perinatal mortality rate (OR =5.78; 95% CI 2.89-11.21). Almost 14% of
      women required admission to augmented care. The most virulent organisms were
      Group A Streptococcus linked to postpartum sepsis at term and preterm Escherichia
      coli sepsis. CONCLUSIONS: Maternal sepsis is associated with preterm birth, a
      high perinatal mortality rate and nulliparous women.

PMID- 24862294
TI  - Implementation of a participatory management model: analysis from a political
      perspective.
AB  - AIM: To analyse experiences of managers and nursing staff in the implementation
      of participatory management, specifically processes of decision-making,
      communication and power in a Canadian hospital. BACKGROUND: Implementing a
      Participatory Management Model involves change because it is focused on the needs
      of patients and encourages decentralisation of power and shared decisions.
      METHODS: The study design is qualitative using observational sessions and content
      analysis for data analysis. We used Bolman and Deal's four-frame theoretical
      framework to interpret our findings. RESULTS: Participatory management led to
      advances in care, because it allowed for more dialogue and shared decision
      making. However, the biggest challenge has been that all major changes are still
      being decided centrally by the provincial executive board. CONCLUSIONS: Managers
      and directors are facing difficulties related to this change process, such as the
      resistance to change by some employees and limited input to decision-making
      affecting their areas of responsibility; however, they and their teams are
      working to utilise the values and principles underlying participatory management
      in their daily work practices. IMPLICATIONS FOR NURSING MANAGEMENT: Innovative
      management models encourage accountability, increased motivation and satisfaction
      of nursing staff, and improve the quality of care.

PMID- 24862295
TI  - Limited palatal muscle resection with tonsillectomy: a novel palatopharyngoplasty
      technique for obstructive sleep apnea.
AB  - OBJECTIVE: The ideal palatal surgery for obstructive sleep apnea (OSA) and
      snoring must maintain the airway patency and correct anatomic abnormalities
      without complications. The purpose of this study was to investigate the efficacy
      of limited palatal muscle resection (LPMR) to improve OSA severity. SUBJECTS AND
      METHODS: Twenty-three patients with OSA underwent LPMR. The LPMR was initiated
      with a bilateral tonsillectomy in patients with tonsil size 2 and 3. The LPMR
      consisted of partial resection of palatal muscles (levator veli palatini,
      palatoglossus, and musculus uvulae) with preservation of the uvula and a simple
      double layer suturing. The retropalatal space and the length of soft palate were
      evaluated by magnetic resonance imaging. Subjective outcomes using visual analog
      scales, Epworth Sleepiness Scale, and overnight polysomnography (PSG) data were
      assessed. RESULTS: Six months after the operation, there was significant
      symptomatic improvement in snoring, morning headaches, tiredness, and daytime
      sleepiness. Postoperative magnetic resonance images showed upward and forward
      movement of uvula and soft palate after LPMR. The length of the soft palate was
      significantly shortened and the retropalatal space was significantly increased.
      Postoperative PSG revealed significant improvement in apnea-hypopnea index (AHI)
      and the total sleep time spent with oxygen saturation below 90%, and reduction in
      AHI following PMR was found in all patients. Furthermore, no patient experienced
      velopharyngeal insufficiency, voice changes, and pharyngeal dryness at 6 months
      follow-up. CONCLUSIONS: The LPMR obtained significant improvement in subjective
      and objective outcomes in OSA, with preserved pharyngeal function. PMR is an
      effective and safe technique to treat oropharyngeal obstruction in OSA surgery.

PMID- 24862296
TI  - Video-assisted minithoracotomy approach: technical developments towards totally
      endoscopic sutureless aortic valve replacement.
AB  - BACKGROUND AND AIM OF THE STUDY: Interest in sutureless aortic bioprostheses is
      growing because of the potential advantages that such devices can bring in
      facilitating minimally invasive approaches. Video assistance can potentially
      enhance details of decalcification and sutureless valve sizing. We review the
      feasibility of sutureless aortic valve replacement (AVR) via a minimally invasive
      video-assisted (MIVA) right anterior minithoracotomy. METHODS: Between November
      2012 and November 2013, 21 patients were selected to undergo an AVR using the
      Enable sutureless device (Medtronic, Minneapolis, MN, USA) via a video-assisted
      right second space minithoracotomy. RESULTS: Procedural success of the MIVA
      approach was 95.3% (one conversion to median sternotomy due to severe pleural
      adhesions). Average aortic clamp time was 72.1 +/- 22.1 min. No paravalvular
      leakage was detected at discharge. Thirty-day mortality was 4.7% (one patient,
      pulmonary embolism). CONCLUSIONS: The described approach appears to be safe and
      feasible with adequate clamp times. Video assistance allows optimal visualization
      of the aortic root and accurate valve delivery, without conflict between the
      device, the camera, and the instruments, making this setting an encouraging
      baseline towards the assessment of the totally endoscopic approach.

PMID- 24862297
TI  - Early life stress modulates amygdala-prefrontal functional connectivity:
      implications for oxytocin effects.
AB  - Recent evidence suggests that early life stress (ELS) changes stress reactivity
      via reduced resting state functional connectivity (rs-FC) between amygdala and
      the prefrontal cortex. Oxytocin (OXT) modulates amygdala connectivity and
      attenuates responses to psychosocial stress, but its effect appears to be
      moderated by ELS. Here we first investigate the effect of ELS on amygdala
      prefrontal rs-FC, and examine whether ELS-associated changes of rs-FC in this
      neural circuit predict its response to psychosocial stress. Secondly, we explore
      the joint effect of OXT and ELS on the amygdala-prefrontal circuit. Eighteen
      healthy young males participated in a resting-state fMRI study of OXT effects
      using a double-blind, randomized, placebo-controlled, within-subject crossover
      design. We measured the rs-FC to bilateral amygdalae and subsequently assessed
      changes of state anxiety and prefrontal responses to psychosocial stress.
      Multiple linear regressions showed that ELS, specifically emotional abuse,
      predicted reduced rs-FC between the right amygdala and pregenual anterior
      cingulate cortex (pgACC), which in turn predicted elevated state anxiety after
      psychosocial stress. In subjects with lower ELS scores, stronger pgACC-amygdala
      rs-FC predicted stronger pgACC deactivation during the psychosocial stress task,
      and this rest-task interaction was attenuated by OXT. In subjects with higher ELS
      scores however, the rest-task interaction was altered and OXT showed no
      significant effect. These findings highlight that ELS reduces pgACC-amygdala rs
      FC and alters how rs-FC of this circuit predicts its stress responsiveness. Such
      changes in pgACC-amygdala functional dynamics may underlie the altered
      sensitivity to the effects of OXT after ELS.

PMID- 24862298
TI  - Dual effects of amiodarone on pacemaker currents in hypertrophied ventricular
      myocytes isolated from spontaneously hypertensive rats.
AB  - The pacemaker current If conducted by hyperpolarization-activated cyclic
      nucleotide-gated (HCN) channels plays a critical role in the regulation of
      cardiac automaticity, with If density increased in hypertrophied ventricular
      myocytes. Amiodarone, a highly effective anti-arrhythmic agent, blocks human HCN
      currents and native If under normal conditions. To determine the effects of
      amiodarone under pathological conditions, we monitored If under after both acute
      (0.01, 0.1, 1, 10 and 100 MUmol/L) and chronic (10 MUmol/L) amiodarone treatment
      in ventricular myocytes from spontaneously hypertensive rats (SHR) with left
      ventricular hypertrophy using the whole-cell patch-clamp technique. The If
      current density was significantly greater in SHR ventricular myocytes than in
      cells from healthy normotensive control Wistar-Kyoto (WKY) rats. Acute
      application of amiodarone significantly decreased If density in myocytes from
      both SHR and WKY rats. The inhibition was concentration dependent with an IC50 of
      4.9 +/- 1.2 and 6.9 +/- 1.3 MUmol/L in myocytes from SHR and WKY rats,
      respectively. Amiodarone increased the activation and deactivation times of If in
      myocytes from SHR, although it did not alter the relationship of voltage
      dependent activation and the reversal potential of If in myocytes from SHR.
      Chronic exposure of myocytes from SHR to amiodarone potently inhibited If and
      downregulated HCN2 and HCN4, the major channel subtypes underlying native If , at
      both the mRNA and protein level. These findings indicate that amiodarone inhibits
      If under hypertrophied conditions through dual mechanisms: (i) direct channel
      blockade of If currents; and (ii) indirect suppression via negative regulation of
      HCN channel gene expression. These unique properties of amiodarone may contribute
      to its anti-arrhythmic properties under pathological conditions. 

PMID- 24862299
TI  - Identification of a novel lncRNA in gluteal adipose tissue and evidence for its
      positive effect on preadipocyte differentiation.
AB  - OBJECTIVE: Peripheral lower body fat is associated with lower cardiometabolic
      risk. Physiological differences in gluteal compared with abdominal subcutaneous
      (sc) adipocyte functions are known but the molecular basis for depot differences
      in adipocyte function is poorly understood. Our goal is to identify novel gene
      regulatory pathways that underlie the heterogeneity of human fat distribution.
      METHODS: Abdominal and gluteal adipose tissue aspirates obtained from 35 subjects
      (age = 30 +/- 1.6 years; BMI = 27.3 +/- 1.3 kg/m(2) ) were analyzed using
      Illumina microarrays and confirmed by RT-PCR. The HOTAIR gene was stably
      transfected into primary cultured human abdominal sc preadipocytes using a
      lentivirus and effects on adipogenic differentiation were analyzed. RESULTS: A
      long noncoding RNA, HOTAIR that was expressed in gluteal but not in Abd sc
      adipose tissue was identified. This difference was retained throughout in vitro
      differentiation and was maximal at day 4. Ectopic expression of HOTAIR in
      abdominal preadipocytes produced an increase in differentiation as reflected by a
      higher percentage of differentiated cells, and increased expression of key
      adipogenic genes including PPARgamma and LPL. CONCLUSIONS: HOTAIR is expressed in
      gluteal adipose and may regulate key processes in adipocyte differentiation. The
      role of this lncRNA in determining the metabolic properties of gluteal compared
      with abdominal adipocytes merits further study.

PMID- 24862300
TI  - The change of macular thickness following single-session pattern scan laser
      panretinal photocoagulation for diabetic retinopathy.
AB  - PURPOSE: To identify the incidence and risk factors of macular edema development
      following single-session pattern scan laser panretinal photocoagulation (PRP) for
      eyes with diabetic retinopathy. METHODS: Medical records were reviewed in
      consecutive patients who underwent single-session PRP for diabetic retinopathy.
      The eyes with baseline central subfield retinal thickness (CRT) less than 300 MUm
      were included. RESULTS: Macular edema developed in 11 (8.5%) of 129 eyes 1 months
      after PRP. In the multivariate analysis, baseline CRT (MUm) (odds ratio [OR] =
      1.04, 95% confidence interval [CI] = 1.00-1.08, p = 0.048) and presence of
      intraretinal cystoid spaces or subretinal fluid on spectral-domain optical
      coherence tomography (SD-OCT) images (OR = 38.33; 95% CI = 1.36-1,083.14, p =
      0.032) were significantly associated with macular edema development at 1-month
      visit. Macular edema developed in two (2.1%) of 97 eyes without cystoid spaces or
      subretinal fluid. The macular edema was spontaneously resolved in five (45.5%) of
      11 cases at 3-month visit. CONCLUSIONS: SD-OCT may be helpful in predicting the
      development of macular edema, although the macular edema rarely developed after
      single-session pattern scan laser PRP and was spontaneously resolved in many
      cases.

PMID- 24862302
TI  - Corneal biomechanical properties after LASIK, ReLEx flex, and ReLEx smile by
      Scheimpflug-based dynamic tonometry.
AB  - PURPOSE: To evaluate corneal biomechanical properties after LASIK, ReLEx flex,
      and the flap-free procedure ReLEx smile by Scheimpflug-based dynamic tonometry
      (Corvis ST) and non-contact differential tonometry (Ocular Response Analyzer,
      ORA). METHODS: Patients treated for high myopia (-10.5 to -5.5 diopters,
      spherical equivalent refraction) more than one year previously at Aarhus
      University Hospital were included. Treatments comprised LASIK (35 eyes), ReLEx
      flex (31 eyes), and ReLEx smile (29 eyes). A control group included 31 healthy
      eyes. Cornea-compensated IOP (IOPcc), corneal hysteresis (CH), and corneal
      resistance factor (CRF) were measured with ORA. Corneal applanation and
      deformation were registered with Corvis ST during an air-pulse. RESULTS: Multiple
      linear regression analysis showed that CH and CRF were significantly lower after
      all keratorefractive procedures compared to healthy controls (p < 0.05). No
      significant differences were observed in CH or CRF between the keratorefractive
      groups. Corvis ST showed no differences in radius at highest concavity (HC
      radius), time until first applanation (A1 Time), time until second applanation
      (A2 Time), and deflection length at highest concavity (HC deflection length)
      between groups. LASIK treated eyes had significantly shorter time until highest
      concavity than eyes treated with ReLEx smile (HC Time, p = 0.01). The A1
      deflection length was significantly shorter in the keratorefractive groups
      compared to the healthy controls (p < 0.05). CONCLUSIONS: Keratorefrative
      procedures alter the corneal biomechanical properties with regard to corneal
      hysteresis and corneal resistant factor. The flap-based LASIK and ReLEx flex and
      the flap-free ReLEx smile result in similar reduction in corneal biomechanics
      when evaluated by Corvis ST and ORA.

PMID- 24862301
TI  - Improvement of fluctuations of intraocular pressure after cataract surgery in
      primary angle closure glaucoma patients.
AB  - BACKGROUND: Cataract surgery has been shown to reduce intraocular pressure (IOP)
      in eyes with primary angle closure glaucoma (PACG). In this study, we examined
      IOP fluctuations and circadian IOP patterns before and after cataract surgery in
      PACG patients using the contact lens sensor (CLS) Triggerfish. METHODS: This was
      a prospective open-label study. Ten consecutive patients with PACG were included.
      The patients underwent phacoemulsification and intraocular lens implantation
      (PEA+IOL) surgery. In each eye, IOP fluctuations over 24 h were measured with the
      CLS before and at three months after the surgery. Changes in corneal curvatures
      and anatomic parameters of the anterior chamber were measured by anterior segment
      optical coherence tomography (AS-OCT). RESULTS: The mean IOP was significantly
      reduced from 14.7 +/- 1.5 mmHg to 11.2 +/- 2.2 mmHg at three months after the
      surgery in PACG patients (P = 0.002). Although the mean range of 24-h IOP
      fluctuations was not significantly changed after the surgery (P = 0.49), the mean
      range of IOP fluctuations during the nocturnal period was significantly decreased
      from 246 +/- 61 mVeq to 179 +/- 64 mVeq after the surgery (P = 0.02). After the
      surgery, seven eyes of the ten (70%) showed the same circadian IOP patterns. AS
      OCT showed significant improvements in the anatomic parameters of the anterior
      chamber after the surgery. CONCLUSIONS: Cataract surgery decreased IOP
      fluctuations during the nocturnal period in PACG patients. These effects might
      partly prevent the progression of PACG.

PMID- 24862303
TI  - Calculating the predicted retinal thickness from spectral domain and time domain
      optical coherence tomography - comparison of different methods.
AB  - PURPOSE: To compare the accuracy of different methods of calculating predicted
      central retinal thickness values in order to allow comparison between results of
      spectral-domain optical coherence tomography (SD-OCT) and time-domain OCT (TD
      OCT) devices. METHODS: In a prospective cohort study, 100 consecutive healthy
      individuals without ocular disease underwent sequential scanning with SD-OCT
      (Spectralis OCT) and TD-OCT (Stratus OCT). A group of 60 eyes was used to
      generate the conversion equations, which were tested on the remaining 140 eyes.
      Four equations were used: 1. Mean difference between SD-OCT and TD-OCT; 2.
      Multiplying a ratio by the original retinal thickness; 3. Linear regression
      analysis using retinal thickness; and 4. Regression analysis using retinal
      thickness and spherical equivalent. All four methods were used to calculate
      predicted SD-OCT values from TD-OCT measurements, and vice versa. RESULTS: For
      all four equations, the predicted SD-OCT central retinal thickness values were
      similar to the actual SD-OCT, with mean difference ranging from 0.78 to 1.01 MUm,
      and intraclass correlation coefficients >0.88. Both regression equations and mean
      difference showed greater accuracy, with variation between calculated and actual
      retinal thickness values <=5 MUm in 60% of eyes. In contrast, the ratio method
      was less accurate, with 15.8 % of eyes showing differences >15 MUm. Similar
      results were found for predicted TD-OCT values. CONCLUSIONS: Several methods can
      be used to convert central retinal thickness values from SD-OCT to the predicted
      TD-OCT value, or vice versa, with high degrees of accuracy and reliability. These
      methods may allow comparison of OCT values from SD-OCT and TD-OCT devices in
      clinical trials and standard patient care.

PMID- 24862304
TI  - Bringing high-value care to the inpatient teaching service.

PMID- 24862305
TI  - Strength training improves performance and pedaling characteristics in elite
      cyclists.
AB  - The purpose was to investigate the effect of 25 weeks heavy strength training in
      young elite cyclists. Nine cyclists performed endurance training and heavy
      strength training (ES) while seven cyclists performed endurance training only
      (E). ES, but not E, resulted in increases in isometric half squat performance,
      lean lower body mass, peak power output during Wingate test, peak aerobic power
      output (W(max)), power output at 4 mmol L(-1)[la(-)], mean power output during 40
      min all-out trial, and earlier occurrence of peak torque during the pedal stroke
      (P < 0.05). ES achieved superior improvements in W(max) and mean power output
      during 40-min all-out trial compared with E (P < 0.05). The improvement in 40-min
      all-out performance was associated with the change toward achieving peak torque
      earlier in the pedal stroke (r = 0.66, P < 0.01). Neither of the groups displayed
      alterations in VO2max or cycling economy. In conclusion, heavy strength training
      leads to improved cycling performance in elite cyclists as evidenced by a
      superior effect size of ES training vs E training on relative improvements in
      power output at 4 mmol L(-1)[la(-)], peak power output during 30-s Wingate test,
      W(max), and mean power output during 40-min all-out trial.

PMID- 24862306
TI  - Possible way to reduce fracture rates in patients with traumatic spinal cord
      injury?
AB  - Lower extremity fractures in men with spinal cord injury (SCI) are a major
      problem. The use of thiazide diuretics, a simple and safe intervention, may be
      effective in reducing the risk of fracture in patients with traumatic SCI.
      Furthermore, thiazide diuretics have an added benefit of reducing kidney stone
      formation. 

PMID- 24862307
TI  - Information/education page. Seizures and traumatic brain injury.

PMID- 24862308
TI  - The spleen and sickle cell disease: the sick(led) spleen.
AB  - The spleen has a combined function of immune defence and quality control of
      senescent or altered red cells. It is the first organ injured in sickle cell
      anaemia (SCA) with evidence of hyposplenism present before 12 months in the
      majority of children. Repeated splenic vaso-occlusion leads to fibrosis and
      progressive atrophy of the organ (autosplenectomy), which is generally complete
      by 5 years in SCA. The precise sequence of pathogenic events leading to
      hyposplenism is unknown. Splenic injury is generally silent and progressive. It
      can be clinically overt with acute splenic sequestration of red cells, an
      unpredictable and life-threatening complication in infants. Splenomegaly, with or
      without hypersplenism, can also occur and can coexist with loss of function.
      Hyposplenism increases the susceptibility of SCA children to infection with
      encapsulated bacteria, which is notably reduced by penicillin prophylaxis and
      immunization. Whether hyposplenism indirectly increases the risk of vaso
      occlusion or other circulatory complications remains to be determined. 

PMID- 24862310
TI  - Effect of treatment variation on outcomes in patients with Clostridium difficile.
AB  - PURPOSE: New guidelines for the treatment of Clostridium difficile-associated
      diarrhea were published by the Infectious Disease Society of America (IDSA) in
      2010, however, there has been no literature evaluating the effectiveness of these
      guidelines. The purpose of this study was to examine the clinical outcomes of
      Clostridium difficile infection including death, C difficile infection
      recurrence, toxic megacolon, and surgery between patients who received guideline
      concordant therapy vs guideline-discordant therapy. METHODS: Retrospective case
      control study of hospitalized adults with C difficile infection presenting to a
      420-bed tertiary care referral county teaching hospital. Patients were identified
      by International Classification of Diseases-9th Revision codes, and included if
      they were >=18 years of age and treated for C difficile infection during their
      hospital visit. Complication rates (death, infection recurrence, toxic megacolon,
      and surgery) of patients with C difficile infection were measured to determine if
      following the IDSA guidelines improves outcomes. RESULTS: Only 51.7% of the
      patients' prescribers followed the 2010 IDSA guidelines. Patients whose
      prescribers followed the IDSA guidelines experienced fewer complications than
      patients whose prescribers strayed from the guidelines (17.2% vs 56.3%, P
      <.0001). This difference was mainly due to a reduction in mortality (5.4% vs
      21.8%, P = .0012) and infection recurrence (14% vs 35.6%, P = .0007). Patients
      who presented with severe and complicated disease received guideline-based
      therapy significantly less often than patients with mild disease (19.7%, 35.3%,
      and 81.2%, respectively, P <.0001). CONCLUSIONS: There was a significant
      reduction in C difficile infection recurrence and mortality when prescribers
      followed the IDSA/Society for Healthcare Epidemiology of America guidelines for
      treatment of C difficile infection.

PMID- 24862311
TI  - Pancytopenia in severe hypothyroidism.

PMID- 24862309
TI  - Syncope risk stratification tools vs clinical judgment: an individual patient
      data meta-analysis.
AB  - BACKGROUND: There have been several attempts to derive syncope prediction tools
      to guide clinician decision-making. However, they have not been largely adopted,
      possibly because of their lack of sensitivity and specificity. We sought to
      externally validate the existing tools and to compare them with clinical
      judgment, using an individual patient data meta-analysis approach. METHODS:
      Electronic databases, bibliographies, and experts in the field were screened to
      find all prospective studies enrolling consecutive subjects presenting with
      syncope to the emergency department. Prediction tools and clinical judgment were
      applied to all patients in each dataset. Serious outcomes and death were
      considered separately during emergency department stay and at 10 and 30 days
      after presenting syncope. Pooled sensitivities, specificities, likelihood ratios,
      and diagnostic odds ratios, with 95% confidence intervals, were calculated.
      RESULTS: Thirteen potentially relevant papers were retrieved (11 authors). Six
      authors agreed to share individual patient data. In total, 3681 patients were
      included. Three prediction tools (Osservatorio Epidemiologico sulla Sincope del
      Lazio [OESIL], San Francisco Syncope Rule [SFSR], Evaluation of Guidelines in
      Syncope Study [EGSYS]) could be assessed by the available datasets. None of the
      evaluated prediction tools performed better than clinical judgment in identifying
      serious outcomes during emergency department stay, and at 10 and 30 days after
      syncope. CONCLUSIONS: Despite the use of an individual patient data approach to
      reduce heterogeneity among studies, a large variability was still present.
      Current prediction tools did not show better sensitivity, specificity, or
      prognostic yield compared with clinical judgment in predicting short-term serious
      outcome after syncope. Our systematic review strengthens the evidence that
      current prediction tools should not be strictly used in clinical practice.

PMID- 24862313
TI  - Targeting GluN2B-containing N-Methyl-D-aspartate receptors: design, synthesis,
      and binding affinity evaluation of novel 3-substituted indoles.
AB  - In an effort to improve our knowledge about structure-affinity relationships
      (SARs) for a class of 3-substituted-indole derivatives as GluN2B-containing N
      methyl-D-aspartate-type receptor (NMDAR) ligands, we herein describe the design,
      synthesis, and preliminary screening of a new series of molecules. The in vitro
      determination of binding affinities suggested that 5-hydroxy- and 6-hydroxyindole
      derivatives 12 and 13 were active ligands. Generally, the novel compounds proved
      to be less potent than their homologs previously reported as promising
      neuroprotective agents. In fact, our lead compound 3-(4-benzylpiperidin-1-yl)-1
      (5-hydroxy-1H-indol-3-yl)ethan-1-one (2) was about 10-fold more active than the
      new propan-1-one derivative (12). To rationalize the low potency of the new
      analog 12, docking studies were also performed and the in silico results were
      consistent with the in vitro data. 

PMID- 24862312
TI  - Diabetes mellitus and risk of prostate cancer in the European Prospective
      Investigation into Cancer and Nutrition.
AB  - The current epidemiologic evidence suggests that men with type 2 diabetes
      mellitus may be at lower risk of developing prostate cancer, but little is known
      about its association with stage and grade of the disease. The association
      between self-reported diabetes mellitus at recruitment and risk of prostate
      cancer was examined in the European Prospective Investigation into Cancer and
      Nutrition (EPIC). Among 139,131 eligible men, 4,531 were diagnosed with prostate
      cancer over an average follow-up of 12 years. Multivariable hazard ratios (HR)
      and 95% confidence intervals (CI) were estimated using Cox proportional hazards
      models stratified by EPIC-participating center and age at recruitment, and
      adjusted for education, smoking status, body mass index, waist circumference, and
      physical activity. In a subset of men without prostate cancer, the cross
      sectional association between circulating concentrations of androgens and insulin
      like growth factor proteins with diabetes status was also investigated using
      linear regression models. Compared to men with no diabetes, men with diabetes had
      a 26% lower risk of prostate cancer (HR, 0.74; 95% CI, 0.63-0.86). There was no
      evidence that the association differed by stage (p-heterogeneity, 0.19) or grade
      (p-heterogeneity, 0.48) of the disease, although the numbers were small in some
      disease subgroups. In a subset of 626 men with hormone measurements, circulating
      concentrations of androstenedione, total testosterone and insulin-like growth
      factor binding protein-three were lower in men with diabetes compared to men
      without diabetes. This large European study has confirmed an inverse association
      between self-reported diabetes mellitus and subsequent risk of prostate cancer. 

PMID- 24862314
TI  - The confinement induced resonance in spin-orbit coupled cold atoms with Raman
      coupling.
AB  - The confinement induced resonance provides an indispensable tool for the
      realization of the low-dimensional strongly interacting quantum system. Here, we
      investigate the confinement induced resonance in spin-orbit coupled cold atoms
      with Raman coupling. We find that the quasi-bound levels induced by the spin
      orbit coupling and Raman coupling result in the Feshbach-type resonances. For
      sufficiently large Raman coupling, the bound states in one dimension exist only
      for sufficiently strong attractive interaction. Furthermore, the bound states in
      quasi-one dimension exist only for sufficient large ratio of the length scale of
      confinement to three dimensional s-wave scattering length. The Raman coupling
      substantially changes the confinement-induced resonance position. We give a
      proposal to realize confinement induced resonance through increasing Raman
      coupling strength in experiments. 

PMID- 24862315
TI  - Prepuberal intranasal dopamine treatment in an animal model of ADHD ameliorates
      deficient spatial attention, working memory, amino acid transmitters and synaptic
      markers in prefrontal cortex, ventral and dorsal striatum.
AB  - Intranasal application of dopamine (IN-DA) has been shown to increase motor
      activity and to release DA in the ventral (VS) and dorsal striatum (DS) of rats.
      The aim of the present study was to assess the effects of IN-DA treatment on
      parameters of DA and excitatory amino acid (EAA) function in prepuberal rats of
      the Naples high-excitability (NHE) line, an animal model for attention-deficit
      hyperactivity disorder (ADHD) and normal random bred (NRB) controls. NHE and NRB
      rats were daily administered IN-DA (0.075, 0.15, 0.30 mg/kg) or vehicle for 15
      days from postnatal days 28-42 and subsequently tested in the Lat maze and in the
      Eight-arm radial Olton maze. Soluble and membrane-trapped L-glutamate (L-Glu) and
      L-aspartate (L-Asp) levels as well as NMDAR1 subunit protein levels were
      determined after sacrifice in IN-DA- and vehicle-treated NHE and NRB rats in
      prefrontal cortex (PFc), DS and VS. Moreover, DA transporter (DAT) protein and
      tyrosine hydroxylase (TH) levels were assessed in PFc, DS, VS and mesencephalon
      (MES) and in ventral tegmental area (VTA) and substantia nigra, respectively. In
      NHE rats, IN-DA (0.30 mg/kg) decreased horizontal activity and increased
      nonselective attention relative to vehicle, whereas the lower dose (0.15 mg/kg)
      increased selective spatial attention. In NHE rats, basal levels of soluble EAAs
      were reduced in PFc and DS relative to NRB controls, while membrane-trapped EAAs
      were elevated in VS. Moreover, basal NMDAR1 subunit protein levels were increased
      in PFc, DS and VS relative to NRB controls. In addition, DAT protein levels were
      elevated in PFc and VS relative to NRB controls. IN-DA led to a number of changes
      of EAA, NMDAR1 subunit protein, TH and DAT protein levels in PFc, DS, VS, MES and
      VTA, in both NHE and NRB rats with significant differences between lines. Our
      findings indicate that the NHE rat model of ADHD may be characterized by (1)
      prefrontal and striatal DAT hyperfunction, indicative of DA hyperactivty, and (2)
      prefrontal and striatal NMDA receptor hyperfunction indicative of net EAA
      hyperactivty. IN-DA had ameliorative effects on activity level, attention, and
      working memory, which are likely to be associated with DA action at inhibitory D2
      autoreceptors, leading to a reduction in striatal DA hyperactivity and, possibly,
      DA action on striatal EAA levels, resulting in a decrease of striatal EAA
      hyperfunction (with persistence of prefrontal EAA hyperfunction). Previous
      studies on IN-DA treatment in rodents have indicated antidepressant, anxiolytic
      and anti-parkinsonian effects in relation to enhanced central DAergic activity.
      Our present results strengthen the prospects of potential therapeutic
      applications of intranasal  DA by indicating an enhancement of selective
      attention and working memory in a deficit model. 

PMID- 24862316
TI  - Nanotherapy for posterior eye diseases.
AB  - It is assumed that more than 50% of the most enfeebling ocular diseases have
      their origin in the posterior segment. Furthermore, most of these diseases lead
      to partial or complete blindness, if left untreated. After cancer, blindness is
      the second most dreaded disease world over. However, treatment of posterior eye
      diseases is more challenging than the anterior segment ailments due to a series
      of anatomical barriers and physiological constraints confronted for delivery to
      this segment. In this regard, nanostructured drug delivery systems are proposed
      to defy ocular barriers, target retina, and act as permeation enhancers in
      addition to providing a controlled release. Since an important step towards
      developing effective treatment strategies is to understand the course or a route
      a drug molecule needs to follow to reach the target site, the first part of the
      present review discusses various pathways available for effective delivery to and
      clearance from the posterior eye. Promise held by nanocarrier systems, viz.
      liposomes, nanoparticles, and nanoemulsion, for effective delivery and selective
      targeting is also discussed with illustrative examples, tables, and flowcharts.
      However, the applicability of these nanocarrier systems as self-administration
      ocular drops is still an unrealized dream which is in itself a huge technological
      challenge.

PMID- 24862317
TI  - The development of site-specific drug delivery nanocarriers based on receptor
      mediation.
AB  - Since they were first reported in 1980, site-specific drug delivery nanocarriers
      have progressed greatly with the development of nanotechnology and biotechnology,
      especially in the anti-tumor field. Currently, some of the ligand peptides like
      RGD have become hot targeting molecules with extensive academic studies and some
      receptor-medicated nanocarriers are now in clinical trials. Homing peptides have
      been the preferred ligands thus far due to their low molecular weight, low
      antigenicity, high modification ratios and low interference in vivo. The major
      benefit of receptor-mediated nanocarriers over passive ones may be their
      accumulation within tumors for longer period of time due to their binding to
      and/or their uptake by cancer cells, preventing them from fast redistribution
      into systemic circulation. The studies on receptor-mediated nanocarriers are very
      dynamic currently, advancing gradually from these against non-therapeutic targets
      to these against therapeutic targets. And recently, more studies were focused on
      these systems against multiple receptors and the combination therapies with
      receptor-mediated nanocarriers. However, we still face great challenges,
      especially in the understanding of receptors, the key issue for receptor-mediated
      delivery. This review presents the past and ongoing studies on various types of
      drug delivery systems based on receptor mediation, discusses the prospective and
      challenges, and introduces the possible trend of study in the future.

PMID- 24862318
TI  - Anticancer polymeric nanomedicine bearing synergistic drug combination is
      superior to a mixture of individually-conjugated drugs.
AB  - Paclitaxel and doxorubicin are potent anticancer drugs used in the clinic as mono
      therapies or in combination with other modalities to treat various neoplasms.
      However, both drugs suffer from side effects and poor pharmacokinetics. These two
      drugs have dissimilar physico-chemical properties, pharmacokinetics and distinct
      mechanisms of action, toxicity and drug resistance. In order to target both drugs
      selectively to the tumor site, we conjugated them at a synergistic ratio to a
      biocompatible and biodegradable polyglutamic acid (PGA) backbone. Drugs
      conjugation to a nano-sized polymer enabled preferred tumor accumulation by
      passive targeting, making use of the enhanced permeability and retention (EPR)
      effect. The rational design presented here resulted in co-delivery of combination
      of the drugs and their simultaneous release at the tumor site. PGA-paclitaxel
      doxorubicin nano-sized conjugate exhibited superior anti-tumor efficacy and
      safety compared to the combination of the free drugs or a mixture of the drugs
      conjugated to separate polymer chains, at equivalent concentrations. This novel
      polymer-based multi-drug nano-sized conjugate allowed for true combination
      therapy since it delivered both drugs to the same target site at the ratio
      required for synergism. Using mice bearing orthotopic mammary adenocarcinoma, we
      demonstrate here the advantage of a combined polymer therapeutic bearing two
      synergistic drugs on the same polymer backbone, compared to each drug bound
      separately to the backbone. 

PMID- 24862319
TI  - The potential and advances in RNAi therapy: chemical and structural modifications
      of siRNA molecules and use of biocompatible nanocarriers.
AB  - Small interfering RNA (siRNA) has attracted great attention as a potential new
      drug due to its highly sequence-specific gene silencing ability and generality in
      therapeutic target. However, the medical applications of siRNA have been severely
      hindered by the lack of an optimal systemic delivery methodology. This poor
      delivery performance of siRNA is mainly caused by its inherent physicochemical
      properties including short and stiff structure, low charge density and
      vulnerability to nuclease cleavage. Thus, the successful development of efficient
      systemic delivery platform for siRNA is a fundamental requirement necessary to
      bring siRNA-based drugs to the market. Herein, we describe some siRNA delivery
      methods based on the chemical and structural modifications of delivery materials
      and siRNA itself to carry siRNA therapeutics safely to the targeted place without
      adverse effects. This review particularly explains the latest progress of
      chemically and structurally modified siRNA polymer (poly-siRNA)-based delivery
      systems. The stable and compact siRNA polyplexes, which are formed by poly-siRNA
      and different types of biocompatible materials, can enhance serum stability and
      target delivery efficiency in vitro and in vivo. In addition, this review
      provides specific information on poly-siRNA delivery systems from basics to
      therapeutic applications in different animal disease models.

PMID- 24862320
TI  - Prevention effect of orally active heparin conjugate on cancer-associated
      thrombosis.
AB  - Thrombogenesis is a major cause of morbidity and mortality in cancer patients.
      Prophylaxis with low-molecular-weight heparin (LMWH) is recommended for cancer
      patients, but requires non-parenteral delivery methods for long-term treatments.
      In this study, we sought to generate a new oligomeric-bile acid conjugate of LMWH
      that can be used for oral delivery. We first synthesized a tetramer of
      deoxycholic acid (tetraDOCA), which was site-specifically conjugated at the end
      saccharide of LMWH. When LMWH-tetraDOCA conjugate (LHe-tetraD) was orally
      administered at a dose of 5 mg/kg in ICR mice, the maximum anti-factor Xa level
      was increased up to 0.62+/-0.05 IU/mL without any evidence of liver toxicity,
      gastrointestinal damage, or thrombocytopenia. The cancer-associated thrombosis
      was induced in tumor-bearing mice by local heat application, and the fibrin
      deposition in tumors was evaluated. The oral administration of LHe-tetraD (either
      a single dose or multiple daily doses for up to 10 days) in mice substantially
      abolished the coagulation-dependent tropism of fibrinogen in the heated tumors
      and significantly decreased hemorrhage, compared to the mice treated with saline
      or subcutaneous injection of LMWH. Thus, the anticoagulation effect of oral LHe
      tetraD invokes the benefits of oral delivery and promises to provide an effective
      and convenient treatment for cancer patients at risk of thrombosis.

PMID- 24862321
TI  - Sustained-release from nanocarriers: a review.
AB  - Nanocarriers have been explored for delivering drugs and other bioactive
      molecules for well over 35years. Since the introduction of Doxil(r), a
      nanoliposomal delivery system for the cancer drug doxorubicin, several products
      have been approved worldwide. The majority of these products focus on cancer
      chemotherapy, and utilize the size advantage of nanocarriers to obtain a
      favourable distribution of the drug carrier in the human body. In general, such
      carriers do not sustain drug release over more than a few days at best. In this
      review, we explore the reasons for this, and present an overview of successful
      research that is capable of generating sustained-release products in non-cancer
      applications. A variety of nanocarriers have been studied, and their advantages
      and shortcomings are highlighted in this review. The achievement of sustained
      release of bioactive molecules opens new doors in nanotherapeutics.

PMID- 24862323
TI  - Albumin-Beyond Fluid Replacement in Cardiopulmonary Bypass Surgery: Why, How, and
      When?
AB  - Maintaining vascular barrier competence, preventing interstitial edema, and
      keeping microcirculation intact is crucial to achieve an optimal outcome in
      cardiopulmonary bypass surgery (CPB). Blood contact with roller pumps and foreign
      surfaces during CPB induces shear stress and a pressure drop across the pump boot
      that leads to transient systemic activation of the inflammatory and hemostatic
      systems. Moreover, patients after CPB often need volume resuscitation using the
      smallest possible amount of colloid solution because of fluid overload. For this
      purpose, human-derived albumin may be preferred over synthetic colloids because
      CPB priming with albumin preserves oncotic pressure, prevents platelet adhesion,
      and likely induces less consumption of coagulation factors. In patients with
      increased bleeding or renal failure, albumin is a safe alternative because of its
      minimal side effects. Large, randomized clinical trials comparing the benefit of
      albumin versus other fluids are warranted in the future to define albumin's
      distinct role in select high-risk surgical populations. 

PMID- 24862322
TI  - Polymer multilayers loaded with antifungal beta-peptides kill planktonic Candida
      albicans and reduce formation of fungal biofilms on the surfaces of flexible
      catheter tubes.
AB  - Candida albicans is the most common fungal pathogen responsible for hospital
      acquired infections. Most C. albicans infections are associated with the
      implantation of medical devices that act as points of entry for the pathogen and
      as substrates for the growth of fungal biofilms that are notoriously difficult to
      eliminate by systemic administration of conventional antifungal agents. In this
      study, we report a fill-and-purge approach to the layer-by-layer fabrication of
      biocompatible, nanoscale 'polyelectrolyte multilayers' (PEMs) on the luminal
      surfaces of flexible catheters, and an investigation of this platform for the
      localized, intraluminal release of a cationic beta-peptide-based antifungal
      agent. We demonstrate that polyethylene catheter tubes with luminal surfaces
      coated with multilayers ~700nm thick fabricated from poly-l-glutamic acid (PGA)
      and poly-l-lysine (PLL) can be loaded, post-fabrication, by infusion with beta
      peptide, and that this approach promotes extended intraluminal release of this
      agent (over ~4months) when incubated in physiological media. The beta-peptide
      remained potent against intraluminal inoculation of the catheters with C.
      albicans and substantially reduced the formation of C. albicans biofilms on the
      inner surfaces of film-coated catheters. Finally, we report that these beta
      peptide-loaded coatings exhibit antifungal activity under conditions that
      simulate intermittent catheter use and microbial challenge for at least three
      weeks. We conclude that beta-peptide-loaded PEMs offer a novel and promising
      approach to kill C. albicans and prevent fungal biofilm formation on surfaces,
      with the potential to substantially reduce the incidence of device-associated
      infections in indwelling catheters. beta-Peptides comprise a promising new class
      of antifungal agents that could help address problems associated with the use of
      conventional antifungal agents. The versatility of the layer-by-layer approach
      used here thus suggests additional opportunities to exploit these new agents in
      other biomedical and personal care applications in which fungal infections are
      endemic. 

PMID- 24862324
TI  - Production of cellulosic ethanol and enzyme from waste fiber sludge using SSF,
      recycling of hydrolytic enzymes and yeast, and recombinant cellulase-producing
      Aspergillus niger.
AB  - Bioethanol and enzymes were produced from fiber sludges through sequential
      microbial cultivations. After a first simultaneous saccharification and
      fermentation (SSF) with yeast, the bioethanol concentrations of sulfate and
      sulfite fiber sludges were 45.6 and 64.7 g/L, respectively. The second SSF, which
      included fresh fiber sludges and recycled yeast and enzymes from the first SSF,
      resulted in ethanol concentrations of 38.3 g/L for sulfate fiber sludge and 24.4
      g/L for sulfite fiber sludge. Aspergillus niger carrying the endoglucanase
      encoding Cel7B gene of Trichoderma reesei was grown in the spent fiber sludge
      hydrolysates. The cellulase activities obtained with spent hydrolysates of
      sulfate and sulfite fiber sludges were 2,700 and 2,900 nkat/mL, respectively. The
      high cellulase activities produced by using stillage and the significant ethanol
      concentrations produced in the second SSF suggest that onsite enzyme production
      and recycling of enzyme are realistic concepts that warrant further attention.

PMID- 24862325
TI  - Effects of dry brining, liquid smoking and high-pressure treatment on the
      physical properties of aquacultured King salmon (Oncorhynchus tshawytscha) during
      refrigerated storage.
AB  - BACKGROUND: Aquacultured King salmon (Oncorhynchus tshawytscha) pieces were dry
      brined with a salt/brown sugar mix, dipped in liquid smoke for 3 min, vacuum
      packed, high hydrostatic pressure (HHP) treated at 600 or 200 MPa for 5 min and
      stored at 4  degrees C for up to 40 days. RESULTS: The surface redness (average
      a*) of the samples increased after dry brining, then decreased after liquid smoke
      treatment. HHP did not change the outside color of liquid-smoked samples.
      However, the inside color changed depending on pressure. HHP-treated control
      samples without dry brining and liquid smoking changed to a pale pink color. HHP
      at 600 MPa resulted in a significant increase in hardness. Compared with fresh
      samples, dry-brined samples had reduced water activity, while samples dipped in
      liquid smoke had lower pH values. CONCLUSION: Dry brining and liquid smoking
      protect the outside color of salmon against changes caused by HHP. The increase
      in hardness may counteract the softening of the smoked salmon tissue over time.

PMID- 24862326
TI  - HIV-1 Tat disrupts CX3CL1-CX3CR1 axis in microglia via the NF-kappaBYY1 pathway.
AB  - Microglia are critical for the pathogenesis of HIV-associated dementia not only
      by acting as conduits of viral entry but also as reservoirs for productive and
      latent virus infection, and as producers of neurotoxins. Interaction between
      CX3CL1 (fractalkine) and FKN receptor (CX3CR1) is highly functional in the brain,
      and is known to regulate a complex network of paracrine and autocrine
      interactions between neurons and microglia. The aim of the present study was to
      determine which extent of HIV-1 Tat protein causes the alteration of CX3CR1
      expression and to investigate the regulatory mechanism for CX3CR1 expression.
      Here we showed that exposure of primary microglia and BV2 cells to exogenous Tat
      protein resulted in down-regulation of CX3CR1 mRNA and protein expression, with a
      concomitant induction of proinflammatory responses. Next, we further showed that
      NF-kappaB activation by Tat treatment negatively regulated CX3CR1 expression.
      Since a YY1 binding site ~10kb upstream of CX3CR1 promoter was predicted in rats,
      mice and humans, the classical NF-kappaB-YY1 regulatory pathway was considered.
      Our findings indicated that Tat repressed CX3CR1 expression via NF-kappaB-YY1
      regulatory pathway. To gain insight into the effect of Tat on CX3CL1-CX3CR1
      communication, calcium mobilization, MAPK activation and microglial migration,
      respectively, were tested in microglial cells after successive treatment with Tat
      and CX3CL1. The results suggested that Tat disrupted the responses of microglia
      to CX3CL1. Taken together, these results demonstrate that HIV-1 Tat protein
      suppresses CX3CR1 expression in microglia via NF-kappaB-YY1 pathway and
      attenuates CX3CL1-induced functional response of microglia. 

PMID- 24862328
TI  - beta-Catenin/TCF-4 signaling regulates susceptibility of macrophages and
      resistance of monocytes to HIV-1 productive infection.
AB  - Cells of the monocyte/macrophage lineage are an important target for HIV-1
      infection. They are often at anatomical sites linked to HIV-1 transmission and
      are an important vehicle for disseminating HIV-1 throughout the body, including
      the central nervous system. Monocytes do not support extensive productive HIV-1
      replication, but they become more susceptible to HIV-1infection as they
      differentiate into macrophages. The mechanisms guiding susceptibility of HIV-1
      replication in monocytes versus macrophages are not entirely clear. We determined
      whether endogenous activity of beta-catenin signaling impacts differential
      susceptibility of monocytes and monocyte-derived macrophages (MDMs) to productive
      HIV-1 replication. We show that monocytes have an approximately 4-fold higher
      activity of beta-catenin signaling than MDMs. Inducing beta-catenin in MDMs
      suppressed HIV-1 replication by 5-fold while inhibiting endogenous beta-catenin
      signaling in monocytes by transfecting with a dominant negative mutant for the
      downstream effector of beta- catenin (TCF-4) promoted productive HIV-1
      replication by 6-fold. These findings indicate that beta-catenin/TCF-4 is an
      important pathway for restricted HIV-1 replication in monocytes and plays a
      significant role in potentiating HIV-1 replication as monocytes differentiate
      into macrophages. Targeting this pathway may provide a novel strategy to purge
      the latent reservoir from monocytes/macrophages, especially in sanctuary sites
      for HIV-1 such as the central nervous system. 

PMID- 24862330
TI  - Modeling and simulation approach to support dosing and study design requirements
      for treating HIV-related neuropsychiatric disease with the NK1-R antagonist
      aprepitant.
AB  - Psychiatric illness is common in HIV-infected patients and underlines the
      importance for screening not only for cognitive impairment but also for co-morbid
      mental disease. The rationale for combining immunomodulatory neurokinin- 1
      receptor (NK1-R) antagonists with combined antiretroviral therapy (cART) is based
      on multimodal pharmacologic mechanisms. The NK1-R antagonist aprepitant's
      potential utility as a drug for depression is complicated by >99.9% protein
      binding and both enzyme inhibition and induction of CYP3A4. A population-based PK
      model developed from a pilot Phase 1B trial in 19 HIV-infected patients (125 or
      250 mg/d aprepitant for 2 weeks) was modified to account for enzyme induction and
      impact of an exposure enhancer on CYP3A4 metabolism. Likelihood of clinical
      success in depression was assessed based on achievement of target trough plasma
      concentration and evaluated using Monte Carlo simulation. Scenarios were
      generated for varying daily dose (375, 625, 750 and 875 mg), pharmacokinetic
      variability, exposure enhancement (EE), duration (2 and 6 months) and sample size
      (n=12 and 24/arm). Daily dosing of >= 625 mg with EE yielded desirable troughs
      (based on in vitro infectivity experiments) of > 2.65 ug/mL for the majority of
      virtual patients simulated. Results are dependent on the degree of exposure
      enhancement and extent of enzyme induction. Actual threshold exposure
      requirements for aprepitant in HIV-associated depression are unknown though
      preclinical evidence supports trough levels > 2.65 ug/mL. If 100% NK1r blockage
      is necessary for efficacy, doses of 875 mg (625 mg with EE) or higher may be
      required. The benefit of aprepitant on innate immunity(natural killer cells) and
      absence of negative effects onex vivo neutrophil chemotaxis alleviates concerns
      regarding drug dependent inhibition (DDI)-mediated infection risk.

PMID- 24862327
TI  - Heme oxygenase-1 dysregulation in the brain: implications for HIV-associated
      neurocognitive disorders.
AB  - Heme oxygenase-1 (HO-1) is a highly inducible and ubiquitous cellular enzyme that
      subserves cytoprotective responses to toxic insults, including inflammation and
      oxidative stress. In neurodegenerative diseases such as Alzheimer's disease,
      Parkinson's disease and multiple sclerosis, HO-1 expression is increased,
      presumably reflecting an endogenous neuroprotective response against ongoing
      cellular injury. In contrast, we have found that in human immunodeficiency virus
      (HIV) infection of the brain, which is also associated with inflammation,
      oxidative stress and neurodegeneration, HO-1 expression is decreased, likely
      reflecting a unique role for HO-1 deficiency in neurodegeneration pathways
      activated by HIV infection. We have also shown that HO-1 expression is
      significantly suppressed by HIV replication in cultured macrophages which
      represent the primary cellular reservoir for HIV in the brain. HO-1 deficiency is
      associated with release of neurotoxic levels of glutamate from both HIV-infected
      and immune-activated macrophages; this glutamate-mediated neurotoxicity is
      suppressed by pharmacological induction of HO-1 expression in the macrophages.
      Thus, HO-1 induction could be a therapeutic strategy for neuroprotection against
      HIV infection and other neuroinflammatory brain diseases. Here, we review various
      stimuli and signaling pathways regulating HO-1 expression in macrophages, which
      could promote neuronal survival through HO-1-modulation of endogenous antioxidant
      and immune modulatory pathways, thus limiting the oxidative stress that can
      promote HIV disease progression in the CNS. The use of pharmacological inducers
      of endogenous HO-1 expression as potential adjunctive neuroprotective
      therapeutics in HIV infection is also discussed. 

PMID- 24862331
TI  - Macrophage derived cystatin B/cathepsin B in HIV replication and
      neuropathogenesis.
AB  - Mononuclear phagocytes including monocytes and macrophages, are important defense
      components of innate immunity, but can be detrimental in HIV-1 infection by
      serving as the principal reservoirs of virus in brain and triggering a strong
      immune response. These viral reservoirs represent a challenge to HIV-1
      eradication since they continue producing virus in tissue despite antiretroviral
      therapy. HIV-1 associated neurocognitive disorders (HAND) involve alterations to
      the blood-brain barrier and migration of activated HIV-1 infected monocytes to
      the brain with subsequent induced immune activation response. Our group recently
      showed that HIV replication in monocyte-derived macrophages is associated with
      increased cystatin B. This cysteine protease inhibitor also inhibits the
      interferon-induced antiviral response by decreasing levels of tyrosine
      phosphorylated STAT-1. These recent discoveries reveal novel mechanisms of HIV
      persistence that could be targeted by new therapeutic approaches to eliminate HIV
      in macrophage reservoirs. However, cystatin B has been also associated with
      neuroprotection. Cystatin B is an inhibitor of the cysteine protease cathepsin B,
      a potent neurotoxin. During HIV-1 infection cystatin B and cathepsin B are
      upregulated in macrophages. Reduction in cystatin/cathepsin interactions in
      infected macrophages leads to increased cathepsin B secretion and activity which
      contributes to neuronal apoptosis. Increased intracellular expression of both
      proteins was recently found in monocytes from Hispanic women with HAND. These
      findings provide new evidence for the role of cathepsin /cystatin system in the
      neuropathogenesis induced by HIV-infected macrophages. We summarize recent
      research on cystatin B and one of its substrates, cathepsin B, in HIV replication
      in macrophages and neuropathogenesis. 

PMID- 24862332
TI  - Brain inflammation is a common feature of HIV-infected patients without HIV
      encephalitis or productive brain infection.
AB  - HIV-associated neurocognitive disorders (HAND) describes different levels of
      neurocognitive impairment, which are a common complication of HIV infection. The
      most severe of these, HIV-associated dementia (HIV-D), has decreased in incidence
      since the introduction of combination antiretroviral therapy (cART), while an
      increase in the less severe, minor neurocognitive disorder (MND), is now seen.
      The neuropathogenesis of HAND is not completely understood, however macrophages
      (MPhi)s/microglia are believed to play a prominent role in the development of the
      more severe HIV-D. Here, we report evidence of neuroinflammation in autopsy
      tissues from patients with HIV infection and varying degrees of neurocognitive
      impairment but without HIV encephalitis (HIVE). MPhi/microglial and astrocyte
      activation is less intense but similar to that seen in HIVE, one of the
      neuropathologies underlying HIV-D. MPhis and microglia appear to be activated, as
      determined by CD163, CD16, and HLA-DR expression, many having a rounded or
      ramified morphology with thickened processes, classically associated with
      activation. Astrocytes also show considerable morphological alterations
      consistent with an activated state and have increased expression of GFAP and
      vimentin, as compared to seronegative controls. Interestingly, in some areas,
      astrocyte activation appears to be limited to perivascular locations, suggesting
      events at the blood-brain barrier may influence astrocyte activity. In contrast
      to HIVE, productive HIV infection was not detectable by tyramide signal-amplified
      immunohistochemistry or in situ hybridization in the CNS of HIV infected persons
      without encephalitis. These findings suggest significant CNS inflammation, even
      in the absence of detectable virus production, is a common mechanism between the
      lesser and more severe HIV-associated neurodegenerative disease processes and
      supports the notion that MND and HIV-D are a continuum of the same disease. 

PMID- 24862336
TI  - Reactivity of graphene and hexagonal boron nitride in-plane heterostructures with
      oxygen: a DFT study.
AB  - A density-functional study has been undertaken to investigate the chemical
      properties of in-plane heterostructures of graphene and hexagonal boron nitride.
      The interactions of armchair and zigzag linking edges with oxygen are looked at
      in detail. The results of the calculations indicate that the linking edges are
      highly reactive to oxygen atoms and predict that oxygen molecules can accordingly
      be adsorbed dissociatively. Furthermore, because oxygen atoms cooperatively
      interact with the heterostructures, the process can lead to opening of the
      linking edges, thus splitting the two materials. 

PMID- 24862335
TI  - Modelling the genetic contribution to mental illness: a timely end for the
      psychiatric rodent?
AB  - Rodent models are a key factor in the process of translating psychiatric genetics
      and genomics findings, allowing us to shed light on how risk-genes confer changes
      in neurobiology by merging different types of data across fields, from
      behavioural neuroscience to the burgeoning omics (e.g. genomics, epigenomics,
      proteomics, etc.). Moreover, they also provide an indispensable first step for
      drug discovery. However, recent evidence from both clinical and genetic studies
      highlights possible limitations in the current methods for classifying
      psychiatric illness, as both symptomology and underlying genetic risk are found
      to increasingly overlap across disorder diagnoses. Meanwhile, integration of data
      from animal models across disorders is currently limited. Here, we argue that
      behavioural neuroscience is in danger of missing informative data because of the
      practice of trying to 'diagnose' an animal model with a psychiatric illness. What
      is needed is a shift in emphasis, from seeking to ally an animal model to a
      specific disorder, to one focused on a more systematic assessment of the
      neurobiological and behavioural outcomes of any given genetic or environmental
      manipulation. 

PMID- 24862334
TI  - Cognitive consequences of a sustained monocyte type 1 IFN response in HIV-1
      infection.
AB  - With successful antiretroviral therapy, HIV-1-infected subjects can achieve
      undetectable peripheral viral loads and immune homeostasis. However, in a subset
      of individuals on therapy, peripheral monocytes have a gene expression profile
      characteristic of a type 1 interferon alpha (IFN) response. This type 1 IFN
      response correlates with a number of pathogenic conditions including neural cell
      injury and in combination with HCV infection, cognitive impairment. Lessons from
      the non-human primate models of pathogenic and nonpathogenic SIV suggest that
      returning the initial IFN spike in acute SIV infection to normal allows the
      immune system to control infection and return to homeostasis. An IFN "alarm"
      signature, defined as monocyte activation with overexpression of the type1 IFN
      genes IFI27 and CD169, would be useful for identifying a subset of subjects with
      HIV-1 infection that could progress to a number of pathologies associated with
      immune activation including cognitive dysfunction. This strategy is being
      actively pursued for autoimmune diseases that are characterized by an IFN
      signature. Therapies to block the IFN signature are under investigation as a
      means to reset the immune system and in a subset of HIV-1-infected subjects may
      be an adjuvant to standard antiviral therapy to return cognitive function. 

PMID- 24862337
TI  - Quantitative muscle ultrasound in Duchenne muscular dystrophy: a comparison of
      techniques.
AB  - INTRODUCTION: Muscle pathology in Duchenne muscular dystrophy (DMD) can be
      quantified using ultrasound by measuring either the amplitudes of sound-waves
      scattered back from the tissue [quantitative backscatter analysis (QBA)] or by
      measuring these backscattered amplitudes after compression into grayscale levels
      (GSL) obtained from the images. METHODS: We measured and compared QBA and GSL
      from 6 muscles of 25 boys with DMD and 25 healthy subjects, aged 2-14 years, with
      age and, in DMD, with function (North Star Ambulatory Assessment). RESULTS: Both
      QBA and GSL were measured reliably (intraclass correlation >= 0.87) and were
      higher in DMD than controls (P < 0.0001). In DMD, average QBA and GSL measured
      from superficial regions of muscle increased (rho >= 0.47, P < 0.05) with both
      higher age and worse function; in contrast, GSL measured from whole regions of
      muscle did not. CONCLUSIONS: QBA and GSL measured from superficial regions of
      muscle can similarly quantify muscle pathology in DMD.

PMID- 24862338
TI  - A comparative study of the use of selective digestive decontamination prophylaxis
      in living-donor liver transplant recipients.
AB  - INTRODUCTION: Bacterial infections are major causes of early morbidity and
      mortality after liver transplantation. Selective digestive decontamination (SDD)
      can be used pre-operatively for living-donor liver transplant (LD-LT), but its
      role in this setting remains controversial. METHODS: To evaluate this strategy,
      we retrospectively analyzed a cohort of consecutive LD-LTs performed in our
      center from March 2007 to February 2011 and compared the incidence and nature of
      early infectious complications, length of intensive care unit stay and
      hospitalization, antibiotic use, and emergence of resistant bacteria in patients
      with or without SDD prophylaxis. RESULTS: Of 148 LD-LTs in the study period, 111
      received SDD prophylaxis while 37 did not. In a multivariate model, the
      independent factors associated with an increased risk of early post-transplant
      infections were length of postoperative mechanical ventilation (for every
      additional day odds ratio [OR] = 2.37, 95% confidence interval [CI] 1.4-4.0; P =
      0.002), and choledochojejunostomy (OR = 4.5, 95% CI 1.95-10.5; P < 0.001). Use of
      SDD did not affect the rate or distribution of infectious complications, duration
      of hospitalization, antibiotic use, or acquisition of resistant bacteria (OR =
      3.52, 95% CI 0.43-15.17; P = 0.376). CONCLUSION: In conclusion, the use of SDD
      prophylaxis in LD-LT was not beneficial and should be avoided, as it offers no
      advantage and could potentiate the emergence of multidrug-resistant organisms.

PMID- 24862339
TI  - Gene expression profiling of Cecropin B-resistant Haemophilus parasuis.
AB  - Synthetically designed antimicrobial peptides (AMPs) present the potential of
      replacing antibiotics in the treatment of bacterial infections. However,
      microbial resistance to AMPs has been reported and little is known regarding the
      underlying mechanism of such resistance. The naturally occurring AMP cecropin B
      (CB) disrupts the anionic cell membranes of Gram-negative bacteria. In this
      study, CB resistance (CBR) was induced in Haemophilusparasuis SH0165 by exposing
      it to a series of CB concentrations. The CB-resistant H.parasuis strains CBR30
      and CBR30-50 were obtained. The growth curves of SH0165 and CBR30 showed that
      CBR30 displayed lower growth rates than SH0165. The result of transmission
      electron microscopy showed cell membranes of the CB-resistant CBR30 and CBR30-50
      were smoother than SH0165. Microarrays detected 257 upregulated and 254
      downregulated genes covering 20 clusters of orthologous groups (COGs) of the CB
      resistant CBR30 compared with SH0165 (>1.5-fold change, p < 0.05). Sixty genes
      were affected in CBR30-50 covering 18 COGs, with 28 upregulated and 32
      downregulated genes. Under the COG function classification, the majority of
      affected genes in the CB-resistant CBR30 and CBR30-50 belong to the category of
      inorganic ion transport, amino acid transport, and metabolism. The microarray
      results were validated by real-time quantitative reverse transcription PCR. This
      study may provide useful guidance for understanding the molecular mechanism
      underlying H.parasuis resistance to CB.

PMID- 24862333
TI  - Monocytes mediate HIV neuropathogenesis: mechanisms that contribute to HIV
      associated neurocognitive disorders.
AB  - HIV infected people are living longer due to the success of combined
      antiretroviral therapy (cART). However, greater than 40-70% of HIV infected
      individuals develop HIV associated neurocognitive disorders (HAND) that continues
      to be a major public health issue. While cART reduces peripheral virus, it does
      not limit the low level, chronic neuroinflammation that is ongoing during the
      neuropathogenesis of HIV. Monocyte transmigration across the blood brain barrier
      (BBB), specifically that of the mature CD14(+)CD16(+) population that is highly
      susceptible to HIV infection, is critical to the establishment of HAND as these
      cells bring virus into the brain and mediate the neuroinflammation that persists,
      even if at low levels, despite antiretroviral therapy. CD14(+)CD16(+) monocytes
      preferentially migrate into the CNS early during peripheral HIV infection in
      response to chemotactic signals, including those from CCL2 and CXCL12. Once
      within the brain, monocytes differentiate into macrophages and elaborate
      inflammatory mediators. Monocytes/macrophages constitute a viral reservoir within
      the CNS and these latently infected cells may perpetuate the neuropathogenesis of
      HIV. This review will discuss mechanisms that mediate transmigration of
      CD14(+)CD16(+) monocytes across the BBB in the context of HIV infection, the
      contribution of these cells to the neuropathogenesis of HIV, and potential
      monocyte/macrophage biomarkers to identify HAND and monitor its progression. 

PMID- 24862340
TI  - Profiling of extensively diversified plant LINEs reveals distinct plant-specific
      subclades.
AB  - A large fraction of eukaryotic genomes is made up of long interspersed nuclear
      elements (LINEs). Due to their capability to create novel copies via error-prone
      reverse transcription, they generate multiple families and reach high copy
      numbers. Although mammalian LINEs have been well described, plant LINEs have been
      only poorly investigated. Here, we present a systematic cross-species survey of
      LINEs in higher plant genomes shedding light on plant LINE evolution as well as
      diversity, and facilitating their annotation in genome projects. Applying a
      Hidden Markov Model (HMM)-based analysis, 59 390 intact LINE reverse
      transcriptases (RTs) were extracted from 23 plant genomes. These fall in only two
      out of 28 LINE clades (L1 and RTE) known in eukaryotes. While plant RTE LINEs are
      highly homogenous and mostly constitute only a single family per genome, plant L1
      LINEs are extremely diverse and form numerous families. Despite their
      heterogeneity, all members across the 23 species fall into only seven L1
      subclades, some of them defined here. Exemplarily focusing on the L1 LINEs of a
      basal reference plant genome (Beta vulgaris), we show that the subclade
      classification level does not only reflect RT sequence similarity, but also
      mirrors structural aspects of complete LINE retrotransposons, like element size,
      position and type of encoded enzymatic domains. Our comprehensive catalogue of
      plant LINE RTs serves the classification of highly diverse plant LINEs, while the
      provided subclade-specific HMMs facilitate their annotation.

PMID- 24862341
TI  - Optical coherence tomography and intravascular ultrasound of double kissing crush
      coronary bifurcation stenting.

PMID- 24862329
TI  - Bioinformatic analysis of HIV-1 entry and pathogenesis.
AB  - The evolution of human immunodeficiency virus type 1 (HIV-1) with respect to co
      receptor utilization has been shown to be relevant to HIV-1 pathogenesis and
      disease. The CCR5-utilizing (R5) virus has been shown to be important in the very
      early stages of transmission and highly prevalent during asymptomatic infection
      and chronic disease. In addition, the R5 virus has been proposed to be involved
      in neuroinvasion and central nervous system (CNS) disease. In contrast, the CXCR4
      utilizing (X4) virus is more prevalent during the course of disease progression
      and concurrent with the loss of CD4(+) T cells. The dual-tropic virus is able to
      utilize both co-receptors (CXCR4 and CCR5) and has been thought to represent an
      intermediate transitional virus that possesses properties of both X4 and R5
      viruses that can be encountered at many stages of disease. The use of
      computational tools and bioinformatic approaches in the prediction of HIV-1 co
      receptor usage has been growing in importance with respect to understanding HIV-1
      pathogenesis and disease, developing diagnostic tools, and improving the efficacy
      of therapeutic strategies focused on blocking viral entry. Current strategies
      have enhanced the sensitivity, specificity, and reproducibility relative to the
      prediction of co-receptor use; however, these technologies need to be improved
      with respect to their efficient and accurate use across the HIV-1 subtypes. The
      most effective approach may center on the combined use of different algorithms
      involving sequences within and outside of the env-V3 loop. This review focuses on
      the HIV-1 entry process and on co-receptor utilization, including bioinformatic
      tools utilized in the prediction of co-receptor usage. It also provides novel
      preliminary analyses for enabling identification of linkages between amino acids
      in V3 with other components of the HIV-1 genome and demonstrates that these
      linkages are different between X4 and R5 viruses. 

PMID- 24862342
TI  - Nebulized hypertonic saline for bronchiolitis in the emergency department: a
      randomized clinical trial.
AB  - IMPORTANCE: Acute bronchiolitis is the most frequent lower respiratory tract
      infection in infants, yet there are no effective therapies available. Current
      evidence is unclear about the role of hypertonic saline (HS) for the acute
      treatment of bronchiolitis. OBJECTIVE: To determine whether nebulized 3% HS
      compared with normal saline (NS) improves respiratory distress in infants with
      bronchiolitis not responding to standard treatments in the emergency department.
      DESIGN, SETTING, AND PARTICIPANTS: A randomized clinical trial with blinding of
      investigators, health care providers, and parents was conducted at a single urban
      pediatric ED. The participants included children aged 2 to less than 24 months
      with their first episode of bronchiolitis and a Respiratory Distress Assessment
      Instrument score of 4 to 15 after nasal suctioning and a trial of nebulized
      albuterol. INTERVENTIONS: Patients were randomized to receive either nebulized 3%
      HS (HS group) or NS (NS group). MAIN OUTCOMES AND MEASURES: The primary outcome
      was change in respiratory distress at 1 hour after the intervention, as measured
      by the Respiratory Assessment Change Score (a decrease indicates improvement).
      Secondary outcomes included vital signs, oxygen saturation, hospitalization,
      physician clinical impression, parental assessment, and adverse events. RESULTS:
      The 31 patients enrolled in each treatment arm had similar baseline demographic
      and clinical characteristics. At 1 hour after the intervention, the HS group
      demonstrated significantly less improvement in the median Respiratory Assessment
      Change Score compared with the NS group (HS, -1 [interquartile range, -5 to 1]
      vs. NS, -5 [interquartile range, -6 to -2]; P = .01). There were no significant
      differences in heart rate, oxygen saturation, hospitalization rate, or other
      outcomes. There were no adverse events. CONCLUSIONS AND RELEVANCE: Infants with
      bronchiolitis and persistent respiratory distress after standard treatment in the
      emergency department had less improvement after receiving 3% HS compared with
      those who received NS. Based on these results and the existing evidence,
      administration of a single dose of 3% HS does not appear to be indicated to treat
      bronchiolitis in the acute care setting. TRIAL REGISTRATION: clinicaltrials.gov
      Identifier: NCT01247064.

PMID- 24862343
TI  - TGFbeta/SMAD4 signalling is inhibited in tumour cells and infiltrating
      lymphocytes of a patient with colon cancer-associated dermatomyositis.

PMID- 24862344
TI  - The Parkinson Anxiety Scale (PAS): development and validation of a new anxiety
      scale.
AB  - Existing anxiety rating scales have limited construct validity in patients with
      Parkinson's disease (PD). This study was undertaken to develop and validate a new
      anxiety rating scale, the Parkinson Anxiety Scale (PAS), that would overcome the
      limitations of existing scales. The general structure of the PAS was based on the
      outcome of a Delphi procedure. Item selection was based on a canonical
      correlation analysis and a Rasch analysis of items of the Hamilton Anxiety Rating
      Scale (HARS) and the Beck Anxiety Inventory (BAI) from a previously published
      study. Validation was done in a cross-sectional international multicenter study
      involving 362 patients with idiopathic PD. Patients underwent a single screening
      session in which the PAS was administered, along with the Hamilton Depression
      Rating Scale, the HARS, and the BAI. The Mini International Neuropsychiatric
      Interview was administered to establish Diagnostic and Statistical Manual of
      Mental Disorders (DSM) diagnoses of anxiety and depressive disorders. The PAS is
      a 12-item observer or patient-rated scale with three subscales, for persistent,
      episodic anxiety and avoidance behavior. Properties for acceptability and
      reliability met predetermined criteria. The convergent and known groups validity
      was good. The scale has a satisfactory factorial structure. The area under the
      receiver operating characteristics curve and Youden index of the PAS are higher
      than that of existing anxiety rating scales. The PAS is a reliable and valid
      anxiety measure for use in PD patients. It is easy and brief to administer, and
      has better clinimetric properties than existing anxiety rating scales. The
      sensitivity to change of the PAS remains to be assessed.

PMID- 24862345
TI  - In situ growth of silver nanoparticles on graphene quantum dots for
      ultrasensitive colorimetric detection of H2O2 and glucose.
AB  - We report a facile green approach for in situ growth of silver nanoparticles
      (AgNPs) on the surface of graphene quantum dots (GQDs). GQDs serve as both
      reducing agent and stabilizer, and no additional reducing agent and stabilizer is
      necessary. The GQDs/AgNPs hybrid exhibits a superior absorbance fading response
      toward the reduction of H2O2. A simple colorimetric procedure is thus proposed
      for ultrasensitive detection of H2O2 without additional chromogenic agent. It
      provides a record detection limit of 33 nM for the detection of H2O2 by the AgNPs
      based sensing system. This colorimetric sensing system is further extended to the
      detection of glucose in combination with the specific catalytic effect of glucose
      oxidase for the oxidation of glucose and formation of H2O2, giving rise to a
      detection limit of 170 nM. The favorable performances of the GQDs/AgNPs hybrid
      are due to the peroxidase-like activity of GQDs. 

PMID- 24862347
TI  - Atrazine degradation using chemical-free process of USUV: analysis of the micro
      heterogeneous environments and the degradation mechanisms.
AB  - The effectiveness of sonolysis (US), photolysis (UV), and sonophotolysis (USUV)
      for the degradation of atrazine (ATZ) was investigated. An untypical kinetics
      analysis was found useful to describe the combined process, which is compatible
      to pseudo first-order kinetics. The heterogeneous environments of two different
      ultrasounds (20 and 400 kHz) were evaluated. The heterogeneous distribution of
      ATZ in the ultrasonic solution was found critical in determining the reaction
      rates at different frequencies. The presence of NaCl would promote/inhibit the
      rates by the growth and decline of "salting out" effect and surface tension. The
      benefits of combining these two processes were for the first time investigated
      from the aspect of promoting the intermediates degradation which were resistant
      in individual processes. UV caused a rapid transformation of ATZ to 2
      hydroxyatrazine (OIET), which was insensitive to UV irradiation; however, US and
      USUV were able to degrade OIET and other intermediates through *OH attack. On the
      other hand, UV irradiation also could promote radical generation via H2O2
      decomposition, thereby resulting in less accumulation of more hydrophilic
      intermediates, which are difficult to degradation in the US process. Reaction
      pathways for ATZ degradation by all three processes are proposed. USUV achieved
      the greatest degree of ATZ mineralization with more than 60% TOC removed,
      contributed solely by the oxidation of side chains. Ammeline was found to be the
      only end-product in both US and USUV processes.

PMID- 24862346
TI  - Cystic fibrosis sputum DNA has NETosis characteristics and neutrophil
      extracellular trap release is regulated by macrophage migration-inhibitory
      factor.
AB  - Neutrophils are the main proinflammatory cell type in chronically infected lungs
      of cystic fibrosis (CF) patients; however, they fail to effectively clear the
      colonizing pathogens. Here, we investigated the molecular composition of non
      mucoid and mucoid Pseudomonas aeruginosa-induced neutrophil extracellular traps
      (NETs) in vitro and compared them to the DNA-protein complexes present in the CF
      sputum. The protein composition of P. aeruginosa-induced NET fragments revealed
      that irrespective of the inducing stimuli, NET fragments were decorated with a
      conserved set of proteins. The DNA-protein complexes derived from CF sputum were
      consistent with NETosis and shared a similar protein signature, suggesting that
      the majority of the extracellular DNA was NET derived. The ability of
      polymorphonuclear leukocytes to produce NETs in response to P. aeruginosa was
      driven by macrophage migration-inhibitory factor (MIF) by promoting mitogen
      activated protein kinase. Analysis of 132 CF patient samples revealed that
      elevated MIF protein levels correlated with poorer lung function. We suggest that
      targeting MIF by small molecular inhibitors might reduce the presence of
      extracellular DNA and serve as an adjunct to the use of antimicrobial drugs that
      could ultimately reduce bacterial fitness in the lungs during the later stages of
      CF disease.

PMID- 24862349
TI  - Dose measurements for dental cone-beam CT: a comparison with MSCT and panoramic
      imaging.
AB  - To date there is a lack of published information on appropriate methods to
      determine patient doses from dental cone-beam computed tomography (CBCT)
      equipment. The goal of this study is to apply and extend the methods recommended
      in the American Association of Physicists in Medicine (AAPM) Report 111 for CBCT
      equipment to characterize dose and effective dose for a range of dental imaging
      equipment. A protocol derived from the one proposed by Dixon et al (2010
      Technical Report 111, American Association of Physicist in Medicine, MD, USA),
      was applied to dose measurements of multi-slice CT, dental CBCT (small and large
      fields of view (FOV)) and a dental panoramic system. The computed tomography dose
      index protocol was also performed on the MSCT to compare both methods. The dose
      distributions in a cylindrical polymethyl methacrylate phantom were characterized
      using a thimble ionization chamber and GafchromicTM film (beam profiles).
      GafchromicTM films were used to measure the dose distribution in an
      anthropomorphic phantom. A method was proposed to extend dose estimates to planes
      superior and inferior to the central plane. The dose normalized to 100 mAs
      measured in the center of the phantom for the large FOV dental CBCT (11.4 mGy/100
      mAs) is two times lower than that of MSCT (20.7 mGy/100 mAs) for the same FOV,
      but approximately 15 times higher than for a panoramic system (0.6 mGy/100 mAs).
      The effective dose per scan (in clinical conditions) found for the dental CBCT
      are 167.60 +/- 3.62, 61.30 +/- 3.88 and 92.86 +/- 7.76 mSv for the Kodak 9000
      (fixed scan length of 3.7 cm), and the iCAT Next Generation for 6 cm and 13 cm
      scan lengths respectively. The method to extend the dose estimates from the
      central slice to superior and inferior slices indicates a good agreement between
      theory and measurement. The GafchromicTM films provided useful beam profile data
      and 2D distributions of dose in phantom. 

PMID- 24862348
TI  - Release of antimony from contaminated soil induced by redox changes.
AB  - Soil contamination by toxic antimony (Sb) released from corroding ammunition has
      become an issue of public concern in various countries. Many of these soils are
      at least occasionally subject to waterlogging; yet mechanisms controlling Sb
      mobility under anaerobic conditions are still poorly understood. We investigated
      Sb concentration and speciation dynamics in a calcareous shooting range soil in
      terms of changing redox conditions using microcosm experiments. The transition to
      reducing conditions invoked by indigenous microbial activity at first led to the
      immobilization of Sb, as Sb(V) was converted to Sb(III), which binds more
      extensively to iron (hydr)oxides. When reducing conditions continued, the
      previously sorbed Sb(III) was gradually released into solution due to reductive
      dissolution of the iron (hydr)oxides. Speciation measurements in the solid phase
      by Sb K-edge XANES spectroscopy and in the soil solution by liquid chromatography
      ICP-MS provided the first evidence that Sb(III) predominated at low redox
      conditions (Eh <0.05 V) in both phases. The results show that Sb(V) is less
      stable in reducing environments than commonly assumed. Given that Sb(III) is
      generally more toxic than Sb(V), the mobilization of Sb(III) under Fe-reducing
      conditions may significantly increase (eco)toxicological risks arising from Sb
      contaminated soils that are prone to flooding or waterlogging.

PMID- 24862350
TI  - Epidemiology of cutaneous leishmaniasis in central Amazonia: a comparison of sex
      biased incidence among rural settlers and field biologists.
AB  - OBJECTIVE: Cutaneous leishmaniasis (CL) is more frequently reported in men than
      in women; this may be due to male-biased exposure to CL vectors, female-biased
      resistance against the disease or both. We sought to determine whether gender
      specific exposure to vector habitats explains male-biased CL incidence in two
      human populations of central Amazonia. METHODS: We compared the CL incidence in
      one population of field researchers (N = 166), with similar exposure for males
      and females, and one population of rural settlers (N = 646), where exposure is
      overall male-biased. We used a combination of questionnaires and clinical data to
      quantify CL cases, and modelled disease incidence in a Bayesian framework.
      RESULTS: There was a moderately higher incidence of CL among men than among women
      in both populations, but male bias decreased as exposure time increased. Disease
      incidence was overall higher among field researchers, suggesting that they are an
      important but understudied CL risk group. CONCLUSION: Our comparison of two
      contrasting populations provided epidemiological evidence that CL incidence can
      be male-biased even when exposure is comparable in both sexes.

PMID- 24862351
TI  - The Loss of Control Over Eating Scale: development and psychometric evaluation.
AB  - OBJECTIVE: This study describes the development, content validity, and convergent
      validity of the Loss of Control over Eating Scale (LOCES). METHOD: An initial
      pool of 56 items covering 13 facets of loss-of-control eating was assembled by
      reviewing qualitative literature, clinical descriptions, and research on binge
      eating. Eating disorder experts (n = 34) and eating disorder clients (n = 22)
      rated each proposed item's clarity and relevance to the construct of loss-of
      control eating, rated 13 facets for their relevance to the construct, and
      provided open-ended feedback about the items and facets. Based on the experts'
      and clients' quantitative and qualitative feedback, scale items were clarified,
      28 items were added, and 10 were deleted. University students (n = 476; 70%
      female, mean age = 20.4 years) completed the resulting 74-item questionnaire,
      rating how often they had the experience identified in the item while eating in
      the last 4 weeks. They also completed the measures of eating disturbance, general
      distress, functional impairment, and general self-control. RESULTS: The resulting
      24-item LOCES (Cronbach's alpha = .96) retained items with highest item-total
      correlations and coverage of the 12 construct facets that experts rated as
      important. The LOCES was significantly correlated with eating disturbances,
      general distress, functional impairment, and general self-control. Three
      subfactors were identified: behavioral, cognitive/dissociative, and
      positive/euphoric aspects of loss-of-control eating. A brief, seven-item version
      of the LOCES was developed and validated. DISCUSSION: A thorough process of
      development, content validation, and psychometric evaluation in multiple samples
      yielded the multifaceted LOCES and its brief form. These instruments may be
      useful in assessing loss-of-control eating in both clinical and nonclinical
      settings.

PMID- 24862352
TI  - Technologically sensed social exposure related to slow-wave sleep in healthy
      adults.
AB  - OBJECTIVE: The aim of this study is to understand the relationship between
      automatically captured social exposure and detailed sleep parameters of healthy
      young adults. METHODS: This study was conducted in a real-world setting in a
      graduate-student housing community at a US university. Social exposure was
      measured using Bluetooth proximity sensing technology in mobile devices. Sleep
      was monitored in a naturalistic setting using a headband sleep monitoring device
      over a period of 2 weeks. The analysis included a total of 11 subjects (6 males
      and 5 females) aged 24-35 (149 subject nights). RESULTS: Slow-wave sleep showed a
      significant positive correlation (Spearman's rho = 0.51, p < 0.0001) with social
      exposure, whereas light non-REM (N1 + N2) sleep and wake time were found to be
      negatively correlated (rho = -0.25, p < 0.01; rho = -0.21, p < 0.01,
      respectively). The correlation of median slow-wave sleep with median social
      exposure per subject showed a strong positive significance (rho = 0.88, p <
      0.001). On average, within subjects, following day's social exposure was higher
      when (slow-wave NREM + REM) percentage was high (Wilcoxon sign-ranked test, p <
      0.05). CONCLUSIONS: Subjects with higher social exposure spent more time in slow
      wave sleep. Following day's social exposure was found to be positively affected
      by previous night's (slow-wave NREM + REM) percentage. This suggests that sleep
      affects following day's social exposure and not vice versa. Capturing an
      individual's dynamic social behavior and sleep from their natural environment can
      provide novel insights into these relationships.

PMID- 24862353
TI  - Penetrating sclerokeratoplasty and autologous pinnal cartilage and conjunctival
      grafting to treat a large limbal melanoma in a dog.
AB  - A four-year-old neutered male Labrador retriever presented to Portland Veterinary
      Specialists Ophthalmology Service for evaluation of a pigmented mass oculus
      sinister (OS) of approximately 4-month duration. Complete ophthalmic examination
      revealed a large, pigmented, raised, well-demarcated, epibulbar mass appearing to
      originate from the nasodorsal limbal region. The mass was smooth and roughly
      circular, extending approximately 4 mm into the sclera and 14 mm into the
      nasodorsal cornea. Gonioscopy directly under the mass was not possible due to
      mass size. The visible iridocorneal angle was normal. High-resolution B-scan
      ultrasound showed mass extension to Descemet's membrane and deep sclera, but no
      intraocular invasion. Penetrating sclerokeratoplasty was performed followed by
      autologous pinnal cartilage and conjunctival grafting to repair the corneoscleral
      defect (20 mm x 19 mm) and to restore globe integrity and function.
      Histopathology confirmed the mass to be a benign limbal melanoma with complete
      excision. The surgery site healed without complication, and the pinnal cartilage
      became fully incorporated into the globe. Twelve months postoperatively, the
      patient remains visual with a normal intraocular and fundic examination. The
      pinnal harvest site on the right ear healed without complication. To the authors'
      knowledge, this is the first reported case of corneoscleral grafting using
      autologous pinnal cartilage. This may represent a viable alternative to other
      corneoscleral grafting procedures for large defects and is an attractive
      treatment option due to lack of host rejection, readily available source of donor
      cartilage, and provision of tectonic support to the globe.

PMID- 24862354
TI  - Transbronchial cryobiopsy in the diagnosis of interstitial lung disease: a cool
      new approach.

PMID- 24862355
TI  - Recent memory for socially transmitted food preferences in rats does not depend
      on the hippocampus.
AB  - The standard model of systems consolidation holds that the hippocampus (HPC) is
      involved only in the initial storage and retrieval of a memory. With time
      hippocampal-neocortical interactions slowly strengthen the neocortical memory,
      ultimately enabling retrieval of the memory without the HPC. Key support for this
      idea comes from experiments measuring memory recall in the socially-transmitted
      food preference (STFP) task in rats. HPC damage within a day or two of STFP
      learning can abolish recall, but similar damage five or more days after learning
      has no effect. We hypothesize that disruption of cellular consolidation outside
      the HPC could contribute to the amnesia with recent memories, perhaps playing a
      more important role than the loss of HPC. This view predicts that intraHPC
      infusion of Tetrodotoxin (TTX), which can block conduction of action potentials
      from the lesion sites, will block the retrograde amnesia in the STFP task. Here
      we confirm the previously reported retrograde amnesia with neurotoxic HPC damage
      within the first day after learning, but show that co-administration of TTX with
      the neurotoxin blocks the retrograde amnesia despite very extensive HPC damage.
      These results indicate that HPC damage disrupts cellular consolidation of the
      recent memory elsewhere; STFP memory may not ever depend on the HPC. 

PMID- 24862356
TI  - Reply to: "Palmitoylethanolamide: problems regarding micronization, ultra
      micronization and additives" Inflammopharmacology DOI:10.1007/s10787-014-0202-3.
AB  - This is a reply to a recently published Commentary: "Palmitoylethanolamide:
      problems regarding micronization, ultra-micronization and additives"
      Inflammopharmacology DOI: 10.1007/s10787-014-0202-3 , written in relation to our
      review article: Skaper SD, Facci L, Fusco M, della Valle MF, Zusso M, Costa B,
      Giusti P (2014) "Palmitoylethanolamide, a naturally occurring disease-modifying
      agent in neuropathic pain" Inflammopharmacology 22:79-94 DOI: 10.1007/s10787-013
      0191-7 . We believe that the Commentary by Kriek contains a number of erroneous
      statements and misinterpretations of the published scientific/medical literature
      which our reply shall elaborate on. Further, the writer of the Commentary has a
      direct connection to a company, JP Russell Science Ltd that sells
      palmitoylethanolamide. The take-home message of our review remains as originally
      stated: "Collectively, the findings presented here propose that
      palmitoylethanolamide merits further consideration as a disease-modifying agent
      for controlling inflammatory responses and related chronic and neuropathic pain".

PMID- 24862357
TI  - Repeated failed non-invasive prenatal testing owing to low cell-free fetal DNA
      fraction and increased variance in a woman with severe autoimmune disease.

PMID- 24862358
TI  - Breast cancer subtype and baseline characteristics from diabetic breast cancer
      patients are not different from nondiabetics.

PMID- 24862359
TI  - Infants under 6 months with bronchiolitis are most likely to need major medical
      interventions in the 5 days after onset.
AB  - AIM: This study examined the need for, and timing of, major medical interventions
      (MMIs) in infants under 6 months of age with bronchiolitis. METHODS: We reviewed
      the medical records of 353 children who visited our emergency department with
      bronchiolitis. MMI was defined as the need for any of the following interventions
      during admission: supplementary oxygen, intravenous fluids, intravenous
      antibiotics or admission to the intensive care unit. RESULTS: Altogether 19% of
      the 353 patients required a MMI and 3% had apnoea. The patients with apnoea were
      all under 2 months of age, and 90% had a respiratory syncytial virus (RSV)
      infection and 40% had been born prematurely. The risk of needing a MMI continued
      for up to 5 days after disease onset. A positive RSV test predicted a MMI with an
      odds ratio (OR) of 11.5 (95% CI 2.6-50.5), and a fever of over 38 degrees C
      predicted a MMI with an OR of 3.5 (95% CI 1.4-8.8). Each 1% increase in the
      initial oxygen saturation value was associated with a decreased risk of MMI (OR
      0.7, 95% CI 0.6-0.8). CONCLUSION: Infants under 6 months of age with
      bronchiolitis were most likely to need MMIs in the first 5 days after disease
      onset.

PMID- 24862360
TI  - Drug prescription for erectile dysfunction before and after diagnosis of
      localized prostate cancer.
AB  - INTRODUCTION: Despite the high prevalence of erectile dysfunction (ED) in men
      with prostate cancer, little is known about the use of ED drugs. Also, the
      possible influence of socioeconomic factors on ED drug use has not been studied
      previously. AIM: The aim of this study was to examine determinants and patterns
      of ED drug use before and after diagnosis in men with localized prostate cancer.
      METHODS: Using a nationwide population-based cohort, 25,390 men with localized
      prostate cancer diagnosed between 2006 and 2009 and 126,944 control men were
      identified and followed for filled ED drug prescriptions over a 3-year period,
      ranging from 1 year before and up to 2 years after diagnosis. MAIN OUTCOME
      MEASURES: The main outcome measure was the proportion of men with at least one
      filled ED drug prescription after diagnosis. RESULTS: The number of men using ED
      drugs increased markedly following diagnosis. Men who underwent radical
      prostatectomy had the strongest increase, with a cumulative proportion of 74% for
      at least one filled prescription within the first 2 years after diagnosis. The
      corresponding proportion was 33% in men treated with radiotherapy, 21% in men on
      active surveillance, 10% in men on watchful waiting, and 8% in control men. Among
      men who underwent prostatectomy, usage attenuated over time. Determinants of
      postdiagnostic use were young age at diagnosis, high income, high education, and
      a low- or intermediate-risk cancer. CONCLUSION: Although drugs for ED are
      commonly prescribed after diagnosis, use among most men is transient and
      influenced by socioeconomic status. Posttreatment counseling and affordable ED
      drugs are likely to reduce treatment dropout and disparities in use and help
      improve sexual health and quality of life in men with prostate cancer.

PMID- 24862361
TI  - Reply: To PMID 23453185.

PMID- 24862362
TI  - An unusual cause of right-sided pleural effusion.

PMID- 24862363
TI  - On the nature of blueshifting hydrogen bonds.
AB  - The block-localized wave function (BLW) method can derive the energetic,
      geometrical, and spectral changes with the deactivation of electron
      delocalization, and thus provide a unique way to elucidate the origin of
      improper, blueshifting hydrogen bonds versus proper, redshifting hydrogen bonds.
      A detailed analysis of the interactions of F(3)CH with NH(3) and OH(2) shows that
      blueshifting is a long-range phenomenon. Since among the various energy
      components contributing to hydrogen bonds, only the electrostatic interaction has
      long-range characteristics, we conclude that the contraction and blueshifting of
      a hydrogen bond is largely caused by electrostatic interactions. On the other
      hand, lengthening and redshifting is primarily due to the short-range n(Y)
      >sigma*(X-H) hyperconjugation. The competition between these two opposing factors
      determines the final frequency change direction, for example, redshifting in
      F(3)CH???NH(3) and blueshifting in F(3)CH???OH(2). This mechanism works well in
      the series F(n)Cl(3)-n CH???Y (n=0-3, Y=NH(3), OH(2), SH(2)) and other systems.
      One exception is the complex of water and benzene. We observe the lengthening and
      redshifting of the O-H bond of water even with the electron transfer between
      benzene and water completely quenched. A distance-dependent analysis for this
      system reveals that the long-range electrostatic interaction is again responsible
      for the initial lengthening and redshifting.

PMID- 24862364
TI  - Sources of information used to support quality use of medicines: findings from a
      national survey of nurse practitioners in Australia.
AB  - PURPOSE: The purpose of this study was to investigate the sources, both print and
      electronic formats, which Australian nurse practitioners (NPs) currently use to
      obtain information regarding quality use of medicines (QUM). An additional aim
      was to document NPs' preferences for continuing education in relation to QUM.
      DATA SOURCES: A national electronic survey of Australian NPs was conducted in
      2007 and again in 2010. CONCLUSIONS: Eighty percent of respondents accessed
      information on QUM from professional literature, which may include scholarly
      journal articles, reports, and independent publications. There was a decrease in
      the percentage of respondents who obtained information from drug industry
      representatives. NPs prefer to receive medicines information in an electronic
      form, rather than a paper-based version, and over the time period more NPs are
      utilizing electronic sources rather than paper. IMPLICATIONS FOR PRACTICE: These
      findings provide important insights into medical information products for the
      developers who may be able to use these results to ensure that their products
      meet the needs of NP clinicians. Additionally, the finding that NPs prefer to
      receive their continuing information related to medicines in electronic format,
      but also highly value conference proceedings, may help to inform future planning
      of NP education needs in relation to QUM.

PMID- 24862366
TI  - A redescription of data does not count as a general theory.

PMID- 24862365
TI  - The cytisine derivatives, CC4 and CC26, reduce nicotine-induced conditioned place
      preference in zebrafish by acting on heteromeric neuronal nicotinic acetylcholine
      receptors.
AB  - RATIONALE: Cigarette smoking is one of the most serious health problems worldwide
      and people trying to stop smoking have high rates of relapse. Zebrafish (Danio
      rerio), by combining pharmacological and behavioral assays, is a promising animal
      model for rapidly screening new compounds to induce smoking cessation.
      OBJECTIVES: This study aims to identify possible acetylcholine nicotinic
      receptors (nAChRs) involved in mediating nicotine (NIC)-induced conditioned place
      preference (CPP) in zebrafish and investigate the effect of the CC4 and CC26
      cytisine derivatives in reducing NIC-induced CPP. METHODS: CPP was evaluated
      using a two-compartment chamber, and the zebrafish were given CC4 (0.001-5
      mg/kg), CC26 (0.001-1 mg/kg), cytisine (0.1-2.5 mg/kg), and varenicline (1-10
      mg/kg) alone or with NIC (0.001 mg/kg). Swimming activity was evaluated using a
      square observational chamber. The affinity of the nicotinic ligands for native
      zebrafish brain nAChRs was evaluated by binding studies using [(3)H]-Epibatidine
      (Epi) and [(125)I]-alphaBungarotoxin (alphaBgtx) radioligands, and their subtype
      specificity was determined by means of electrophysiological assay of oocyte
      expressed alpha4beta2 and alpha7 subtypes. RESULTS: CC4 and CC26 induced CPP with
      an inverted U-shaped dose-response curve similar to that of NIC. However, when co
      administered with NIC, they blocked its reinforcing or slightly aversive effect.
      Binding and electrophysiological studies showed that this effect was due to
      binding to high-affinity heteromeric but not alpha7-containing receptors.
      CONCLUSIONS: We have further characterized CC4 and identified a new compound
      (CC26) that may be active in inducing smoking cessation. Zebrafish is a very
      useful model for screening new compounds that can affect the rewarding properties
      of NIC.

PMID- 24862367
TI  - "Mourning" a lost opportunity.

PMID- 24862369
TI  - [Comparison of optical and ultrasound biometry and assessment of using both
      methods in practice].
AB  - PURPOSE: The present study compares accuracy of optical biometry (OB) and
      ultrasound biometry (UB) based on postoperative best corrected visual acuity
      (BCVA) results, and assesses the extent of the usage of the measurement methods
      in current practice. METHODS: 335 eyes in total were operated for cataract at
      Beskydske ocni centrum (Beskydy Eye Centre; BOC), Frydek-Mistek hospital, in the
      period between 7 February 2007 and 7 April 2010. All patients were examined using
      both IOL-Master and Ocu-Scan prior to the surgery. All surgeries were performed
      using microcoaxial phacoemulsification, 2,2 mm incision, implanting IOL AcrySof
      SP, SPN or SPN IQ. BCVA was examined three months after the surgery. We first
      calculated medians of anterior-posterior axial length (AL) values measured using
      both methods; with both the whole set and individual subsets created according to
      the eye length. Difference between the two methods was calculated in mm. We
      calculated accurate dioptric power of the IOL, which should have been implanted
      in the lens bag to ensure postoperative emmetropia, using BCVA results. With each
      eye, we determined the size of diopter variation of the IOLs dioptric power value
      for emmetropia determined by an optical biometer from the accurate value of the
      IOLs dioptric power. Ultrasound biometry results were processed in the same way.
      The SRK-T formula was used for calculation with each biometry. We also calculated
      the number of variations above 1 D and 2 D with both biometric methods. RESULTS:
      The median of axial eye length measured using an optical biometer was 23,08 mm,
      and the median of axial eye length measured using ultrasound biometry was 22,93
      mm. The difference between these values was 0,15 mm (150 microns), which equals
      the difference between average values of coincident measurement results. Average
      variation of dioptric power of an implanted IOL from retrospectively established
      optimum value of the IOLs optical power was 0,40 D lower with optical biometry
      and 0,16 D lower with ultrasound biometry. In the context of assessing the course
      of the curves of both methods created using a polynomial graph, this result
      confirms that the two methods correspond significantly, and therefore selecting
      any of the methods could not negatively impact determination of the implanted
      IOLs dioptric power. Comparing the frequency of variations above 1D and 2,0 D
      with OB and UB from the accurate value of the IOLs dioptric power, we discovered
      a substantially higher percentage of variations with UB - up to 25 % of the total
      set above 1,0 D. CONCLUSION: RESULTS of comparing accuracy and comfort of AL
      measurement with both methods justify unambiguous preference of optical biometry
      over ultrasound biometry in current practice. If measurement using ultrasound
      probe is done correctly, results of both methods correspond significantly, and so
      the methods are mutually replaceable. Using ultrasound biometry is therefore
      adequate in case optical biometry cannot be used.

PMID- 24862370
TI  - [Assessment of postoperative anterior-posterior shift of AcrySof SP lens in time
      and its impact on resulting refraction].
AB  - PURPOSE: The present study assesses the anterior-posterior shift of the AcrySof
      SP intraocular lens in the eye between the third and fifteenth month after
      surgery. METHODS: The observed set contained a total of 241 eyes operated for
      cataract at Beskydske ocni centrum (Beskydy Eye Centre; BOC), Frydek-Mistek
      hospital from 7 February 2007 to 7 April 2010. All surgeries were performed
      through microcoaxial phacoemulsification and a 2,2 mm incision, with intraocular
      lens (IOL) AcrySof type SP implanted. For each eye, we examined BCVA, as well as
      anterior chamber depth by optical biometry (IOL-Master, Carl Zeiss GmbH, Jena), 3
      and 15 months after the surgery. Average depths were calculated and compared; and
      their variations converted from mm to diopters. Based on the BCVA results, we
      were able to determine optimum dioptric power of the IOL, which should have been
      implanted in the eye to ensure postoperative emmetropia. Averages of all values
      were calculated and results thereof compared. RESULTS: We noted a slight average
      deepening of the anterior chamber depth (0,03 mm) causing a hypermetropic shift
      of 0,05 D, insignificant in terms of refraction. Though comparison of average
      optimum IOL values calculated based on examinations carried out 3 and 15 months
      after surgery, we ascertained an actual zero difference between the two values.
      CONCLUSION: Through our own calculations, we verified very good stability of the
      implanted hydrophobic acrylic SP AcrySof lenses in our set, with zero haptic
      angulation. There is de facto no anterior-posterior shift of the IOL between 3
      and 15 months after surgery, and therefore no change in refraction noticeable by
      the patient.

PMID- 24862371
TI  - [Microperimetry in the wet form of age - related macular degeneration (ARMD)].
AB  - Aim of the paper is to introduce and evaluate the microperimetry as a support
      technique in the evaluation of the ARMD wet form bevacizumab (Avastin) treatment
      efficacy. METHODS: Twenty-one patients (21 eyes) with ARMD wet form were included
      in the study; they were examined by means by OCT/SLO (optic coherence tomography
      / scanning laser ophthalmoscope) machine whose part is the microperimetric test.
      In each patient, there were two microperimetric examinations performed - the
      first one was done one day before the application of the treatment and the second
      one one month after the application. The values of retinal sensitivity and
      possible absolute scotomas were recorded by the microperimeter. The best
      corrected visual acuity measurement was recorded as well. RESULTS: The
      measurements were performed in the group of 21 eyes of 8 men and 13 women (age 50
      - 86 years). There were the differences between the genders evaluated (at the
      selected level of significance of 0.05) in the following categories: age, retinal
      sensitivity, absolute scotoma extent, and visual acuity. Differences among men
      and women were found in retinal sensitivity, before the treatment and after it as
      well. The influence of the gender we may exclude, except the category of retinal
      sensitivity. In the categories age, visual acuity, and even absolute scotoma
      extent, no differences between genders were found. The retinal sensitivity (in
      case of fixation up to 4 degrees) improved in the men group from 14.49 dB +/-
      2.44 dB to 15.65 dB +/- 2.61 dB, in the women group from 10.47 dB +/- 3.11 dB to
      12.05 dB +/- 3.10 dB. The visual acuity in the whole group (men + women)
      increased from 0.48 +/- 0.17 to 0.60 +/- 0.18, so improved by 12 %. Statistically
      significant is also the result of the treatment in the absolute scotoma.
      CONCLUSION: Microperimetry is a suitable method to evaluate the function of
      macular region of the retina. The study confirms, that the treatment of wet form
      ARMD by means of intravitreal bevacizumab injections significantly increases the
      retinal sensitivity (in dB), decreases of the extent of absolute scotoma and
      improves the visual acuity by 12 %.

PMID- 24862372
TI  - [Foveal hypoplasia detection by optical coherence tomography].
AB  - PURPOSE: To evaluate the contribution of optical coherence tomography (OCT) in
      the diagnosis of foveal hypoplasia in children. MATERIAL AND METHODS: Children
      with foveal hypoplasia (FH) were examinated with device RTVue Fourier - domain
      (FD) - OCT, software - version 6.8 (Optovue Inc., Fremont, USA). A qualitative
      examination of the macular area was performed with single horizontal scan (1024 A
      scans/frame). Macular thickness was measured and evaluated quantitatively with an
      automatic fast macular area protocol MM5 (Macular Map 5x5 mm). A control group of
      children was used for comparison. RESULTS: The quality was assessed with OCT
      image of the macula and quantitatively evaluated macular thickness and
      configuration in children with foveal hypoplasia. It was subsequently realized
      the comparison of macular OCT findings in healthy children. The OCT showed a
      reduction of foveal depression, continuous extension of the inner retinal layers
      through the area in which should be normally found fovea. Patients with foveal
      hypoplasia had thicker central macula and fovea than children in the control
      group. CONCLUSION: OCT in our group of patients confirmed the final diagnosis of
      foveal hypoplasia. FD-OCT is a noninvasive and quick method helpful in
      identifying retinal abnormalities in the diagnosis of foveal hypoplasia in
      children and may be useful in diagnosing patients with unexplained decrease in
      vision.

PMID- 24862368
TI  - Effects of corticotrophin-releasing factor receptor 1 antagonists on amyloid-beta
      and behavior in Tg2576 mice.
AB  - RATIONALE: Previous studies indicate that psychosocial stressors could accelerate
      amyloid-beta (Abeta) levels and accelerate plaque deposition in mouse models of
      Alzheimer disease (AD). Stressors enhanced the release of corticotrophin
      releasing factor (CRF), and exogenous CRF administration mimicked the effects of
      stress on Abeta levels in mouse models of AD. However, whether CRF receptor 1
      (CRF1) antagonists could influence the stress-induced acceleration of an AD-like
      process in mouse models has not been well studied. OBJECTIVE: We sought to
      examine whether CRF1 antagonists inhibit the effects of isolation stress on
      tissue Abeta levels, Abeta plaque deposition, and behaviors related to anxiety
      and memory in Tg2576 mice, and to investigate the molecular mechanism underlying
      such effects. METHODS: Cohorts of Tg2576 mouse pups were isolated or group-housed
      at 21 days of age, and then the subgroups of these cohorts received daily
      intraperitoneal injections of the CRF1 antagonists, antalarmin or R121919 (5, 10,
      and 20 mg/kg), or vehicle for 1 week. Other cohorts of Tg2576 mouse pups were
      isolated or group-housed at 21 days of age, and then at 4 months of age,
      subgroups of these mice were administered antalarmin (20 mg/kg) or vehicle in
      their drinking water for 6 months. Finally, cultured primary hippocampal neurons
      from regular Tg2576 pups (P0) were incubated with CRF (0.1, 1, and 10 nM),
      antalarmin (100 nM) or H-89 (1 MUM) for 48 h. Brain tissues or cultured neurons
      were collected for histological and biochemical analyses, and behavioral measures
      were collected in the cohorts of mice that were chronically stressed. RESULTS:
      Administration of antalarmin at 20 mg/kg dose for 1 week significantly reduced
      Abeta1-42 levels in isolation stressed mice. Administration of antalarmin for 6
      months significantly decreased plasma corticosterone levels, tissue Abeta1-42
      levels, and Abeta plaque deposition in the brain and blocked the effects of
      isolation stress on behaviors related to anxiety and memory. Finally, incubation
      of neurons with 100 nM antalarmin inhibited the ability of 10 nM CRF to increase
      Abeta1-42 levels and protein kinase A IIbeta expression. The effect of CRF1 on
      Abeta1-42 levels was also diminished by treatment with H-89, a c-AMP/PKA
      inhibitor. CONCLUSIONS: These results suggest that CRF1 antagonists can slow an
      AD-like process in Tg2576 mice and that the c-AMP/PKA signaling pathway may be
      involved in this effect.

PMID- 24862373
TI  - [Optic disc drusen - current diagnostic possibilities].
AB  - Authors present the findings of two patients with optic nerve drusen, and an
      overview of current examination techniques in the diagnostics of optic nerve
      drusen including ultrasound examination, fundus photography, florescein
      angiography, computerized perimetry, auto-florescence fundus examination,
      examination of the nerve fibre layer using optical coherence tomography (OCT) or
      nerve fibres layer analyzer (GDx). In the first case, the patient was recommended
      to be supervised without any therapy. The second patient with regard to perimeter
      finding, loss of nerve fibre layer and increase of the intraocular pressure was
      prescribed local anti-glaucoma therapy.

PMID- 24862374
TI  - [Scleral buckling for rhegmatogenous retinal detachment].
AB  - Rhegmatogenous retinal detachment (RRD) is the separation of the sensory retina
      from the pigment epithelium (RPE). RRD is caused by a retinal tear in the
      periphery and the vitreoretinal (VR) traction, which allows access of the
      vitreous fluid to the subretinal space. Treatment of symptomatic retinal
      detachment is currently surgical only. Surgical options are intraocular and
      extraocular. This is the retrospective evaluation of the group of 17 eyes of 17
      patients with RRD, which were operated by scleral buckling. Patients were 9 men
      and 8 women, age range 19-61 (median 46) years. The observation period is 1-13
      months (median 7). The possible types of external interventions procedure were
      used only two: the radial plombage (in one case double) and cerclage. 15 patients
      (88 %) were phakic, and 2 were pseudophakic. In 12 eyes (71 %) were the quadrant
      RRDs, 2 eyes had dialysis in periphery of the retina, 1x it was the top half and
      1x bottom half, and 1 patient had a subtotal RRD. In 9 (53 %) cases were used
      type of operation cryocoagulation with radial buckle and in 8 cases
      cryocoagulation with the cerclage. In four cases, was injected the gas tamponade
      into the vitreous at the end of the surgery. Primary attaching the retina
      occurred in 16 cases (94 %) and the retina remained flat in 14 eyes (82.4% ), in
      2 cases occurred re-detachment (11.7 %). Preoperative best corrected visual
      acuity (BCVA) ranged from hand movement to 20/20 (average Snellen equivalent
      20/63) and postoperative BCVA was 1/50 - 20/20 (average 20/50). Improving BCVA
      was statistically significant (Wilcoxon p=0.01). We consider the cryosurgical
      procedure for phakic eyes as the gold standard of the surgical treatment of
      uncomplicated rhegmatogenous retinal detachment. The main reason for the eventual
      failure of this technique is persistent vitreous traction and proliferative
      vitreoretinopathy (PVR).

PMID- 24862375
TI  - Coronin-1a is a potential therapeutic target for activated T cell-related immune
      disorders.

PMID- 24862377
TI  - Perceptions of Greek medical students regarding medical profession and the
      specialty selection process during the economic crisis years.
AB  - PURPOSE: To assess the beliefs and preferences of 6th year Greek medical
      students, regarding medical profession and the specialty selection process, in
      the years of financial crisis. SETTING: Democritus University of Thrace, Medical
      School, Alexandroupolis, Greece. MATERIAL AND METHODS: A custom questionnaire
      based on former similar studies was developed and administered to senior medical
      students. Further to demographics, the questionnaire gathered information on
      perceptions and trends regarding medical profession, the specialty and residency
      selection processes. Total question scores were summed for comparisons among
      questions. Mean scores and standard deviations were calculated for comparisons
      between student groups. RESULTS: 111 students responded successfully to the
      instrument. "Helping patients" and the "scientific basis of medicine" were the
      fundamental reasons for choosing the medical profession. Compared to women, male
      students placed greater importance on the "financial allowances" (men: 3.73+/
      1.03, women: 3.05+/-1.30, p=0.01). Regarding the selection criteria for a certain
      specialty, "challenging specialty" and "bedside specialty", were the main
      influence factors. Men more strongly preferred a specialty that could
      "financially support their desired lifestyle" (men: 3.93+/-0.88, women: 3.41+/
      1.30, p=0.02). Concerning selection criteria of a residency program, students
      chose a "well structured" program at a "recognized hospital/department".
      Regarding the country of preference for their residency, 86% planned to continue
      abroad, primarily in Germany and the United Kingdom. CONCLUSION: Greek medical
      students perceive the medical profession and the specialty process in a similar
      way like their colleagues form Western countries. However, the vast majority
      identify that migration to another country is the most promising alternative
      choice for their medical career.

PMID- 24862376
TI  - TLR2 activation causes tachyphylaxis to beta2 -agonists in vitro and ex vivo:
      modelling bacterial exacerbation.
AB  - BACKGROUND: Asthma is a widespread chronic health problem exacerbated by common
      viral and bacterial infections. Further research is required to understand how
      infection worsens asthma control in order to advance therapeutic options in the
      future. Recent research has revealed that beta2 -adrenergic receptor (beta2 -AR)
      agonists lose bronchodilatory efficacy because the receptor-mediated molecular
      pathways responsible for their beneficial actions are desensitized by infection.
      To date, most studies have focussed on viral infection, leaving the impact of
      bacterial infection on beta2 -AR desensitization relatively under-investigated.
      We address this in this study. METHODS AND RESULTS: Utilizing an in vitro model
      of bacterial exacerbation in airway smooth muscle (ASM) cells, we show that
      activation of toll-like receptor 2 (TLR2; mimicking bacterial infection) in the
      presence of an inflammatory stimulus leads to beta2 -AR desensitization. This
      occurs via TLR2-dependent upregulation of cyclooxygenase 2 (COX-2) mRNA
      expression and increased secretion of PGE2 . Importantly, PGE2 causes
      heterologous beta2 -AR desensitization and reduces cAMP production in response to
      short-acting (salbutamol) and long-acting (formoterol) beta2 -agonists. Thus,
      bacterial infectious stimuli act in a PGE2 -dependent manner to severely curtail
      the beneficial actions of beta2 -agonists. The impact of beta2 -AR
      desensitization is demonstrated by reduced gene expression of the critical anti
      inflammatory molecule MKP-1 in response to beta2 -agonists, as well as impaired
      bronchodilation in a mouse lung slices. CONCLUSIONS: Taken together, our results
      show that, like viruses, bacteria induce prostanoid-dependent beta2 -AR
      desensitization on ASM cells. Notably, COX-2 inhibition with the specific
      inhibitor celecoxib represses PGE2 secretion, presenting a feasible
      pharmacological option for treatment of infectious exacerbation in asthma in the
      future.

PMID- 24862378
TI  - Involving patients in a multidisciplinary European consensus process and in the
      development of a 'patient summary of the consensus document for colon and rectal
      cancer care'.
AB  - CONTEXT: High-quality cancer care should be accessible for patients and
      healthcare professionals. Involvement of patients as partners in guideline
      formation and consensus processes is still rarely found. EURECCA, short for
      European Registration of Cancer Care, is the platform to improve outcomes of
      cancer care by reducing variation in the diagnostic and treatment process.
      EURECCA acknowledges the important role of patients in implementation of
      consensus information in clinical practice. OBJECTIVE: The aim of this article is
      to describe the process of involving patients in the consensus process and in
      developing the patient summary of the consensus for colon and rectal cancer care.
      METHODS: The Delphi method for achieving consensus was used. Three online voting
      rounds and one tele-voting round were offered to an expert panel of oncology
      professionals and patient representatives. At four different stages, patients
      and/or patient representatives were involved in the process: (1) during the
      consensus process, (2) lecturing about the role of the patient, (3) development
      of the patient summary, and (4) testing the patient summary. RESULTS:
      Representatives were invited to the voting and commenting rounds of this process
      and given an equal vote. Although patients were not consulted during the planning
      stages of this process, patient involvement increased following the panel's
      discussion of the implementation of the consensus among the patient population.
      After the consensus meeting, the patient summary was written by patient
      representatives, oncologists and nurses. A selection of proactive patients
      reviewed the draft patient summary; responses were positive and several patient
      reported outcomes were added. Questionnaires to evaluate the use and
      implementation of the patient summary in daily practice are currently being
      developed and tested. Patient consultation will be needed in future planning for
      selection of topics. DISCUSSION: The present study may function as a model for
      future consensus processes to involve patients at different stages and to
      implement both patient and healthcare professional versions in daily practice.

PMID- 24862379
TI  - Unilateral painless nasal ulceration.

PMID- 24862380
TI  - Ropivacaine in ultrasound-guided femoral nerve block: what is the minimal
      effective anaesthetic concentration (EC90)?
AB  - The objective of this study was to estimate the minimal effective anaesthetic
      concentrations of ropivacaine required to block the femoral nerve in 90% of
      patients. Forty-five patients who had knee surgery received ultrasound-guided
      femoral nerve block using 15 ml ropivacaine. The ropivacaine concentration given
      to a patient relied on the efficacy of the block in the previous patient, using
      the biased-coin design up-down sequential method. In the event of successful
      block, the next patient was randomly assigned to receive either the same
      ropivacaine concentration or a concentration 0.02% w/v less. In the event of a
      failed block, the next patient received a concentration 0.02% w/v higher.
      Successful block was defined as complete sensory and motor block before surgery
      together with pain-free surgery. The minimal effective ropivacaine concentration
      was estimated to be 0.167% w/v (95% CI 0.14-0.184%). Perineural injection of 15
      ml ropivacaine 0.167% w/v under ultrasound guidance can provide successful
      femoral nerve block in 90% of patients. 

PMID- 24862381
TI  - Reduced activity of 11beta-hydroxylase accounts for elevated 17alpha
      hydroxyprogesterone in preterms.
AB  - OBJECTIVE: To characterize the urinary steroid metabolome of neonates and infants
      born either at term or preterm. STUDY DESIGN: We retrospectively analyzed urinary
      steroid hormone metabolites determined by gas chromatography-mass spectrometry of
      78 neonates and infants born at term and 83 neonates and infants born preterm
      (median 34 weeks of gestational age). The subjects' 11beta-hydroxylase and 21
      hydroxylase activities were assessed on the basis of urinary metabolite substrate
      to-product ratios. RESULTS: Preterm neonates and infants had elevated urinary
      concentrations of 17alpha-hydroxyprogesterone (17OHP) metabolites (P<.001) but
      lower urinary concentrations of the 21-deoxycortisol metabolite pregnanetriolone
      (PTO) (P<.01). One reason was lower 11beta-hydroxylase activity in preterms. We
      could demonstrate a correlation between low 11beta-hydroxylase activity and high
      urinary concentrations of 17OHP metabolites (r=0.51, P<.001) but low urinary
      concentrations of the 21-deoxycortisol metabolite PTO (r=-0.24, P=.03) in
      preterms. CONCLUSIONS: Low 11beta-hydroxylase activity may explain increased
      17OHP but decreased 21-deoxycortisol metabolite excretion in preterms. Our
      analysis clarifies, first, why preterms have higher 17OHP levels and thus higher
      rates of false-positive screening results for congenital adrenal hyperplasia than
      do term infants, and, second, why 21-deoxycortisol or its urinary metabolite PTO
      is more specific than 17OHP for the diagnosis of 21-hydroxylase deficiency.

PMID- 24862382
TI  - Reply: To PMID 23992672.

PMID- 24862384
TI  - C2Analyzer: Co-target-co-function analyzer.
AB  - MicroRNAs (miRNAs) interact with their target mRNAs and regulate biological
      processes at post-transcriptional level. While one miRNA can target many mRNAs, a
      single mRNA can also be targeted by a set of miRNAs. The targeted mRNAs may be
      involved in different biological processes that are described by gene ontology
      (GO) terms. The major challenges involved in analyzing these multitude
      regulations include identification of the combinatorial regulation of miRNAs as
      well as determination of the co-functionally-enriched miRNA pairs. The
      C2Analyzer: Co-target-Co-function Analyzer, is a Perl-based, versatile and user
      friendly web tool with online instructions. Based on the hypergeometric analysis,
      this novel tool can determine whether given pairs of miRNAs are co-functionally
      enriched. For a given set of GO term(s), it can also identify the set of miRNAs
      whose targets are enriched in the given GO term(s). Moreover, C2Analyzer can also
      identify the co-targeting miRNA pairs, their targets and GO processes, which they
      are involved in. The miRNA-miRNA co-functional relationship can also be saved as
      a .txt file, which can be used to further visualize the co-functional network by
      using other software like Cytoscape. C2Analyzer is freely available at
      www.bioinformatics.org/c2analyzer.

PMID- 24862383
TI  - Probiotics for necrotizing enterocolitis: not always a success story.

PMID- 24862385
TI  - Infections in status epilepticus: a retrospective 5-year cohort study.
AB  - PURPOSE: Status epilepticus (SE) has attracted renewed interest lately, and
      efforts are made to optimize every treatment stage. For refractory SE, optimal
      supporting care involves mechanical ventilation and intensive care unit (ICU)
      admission. Infections often complicate SE and recently a single-centre
      observational study demonstrated an association between infections and poor short
      term outcome of SE in a cohort of severely ill patients. We have here attempted
      to replicate those findings in a different cohort. METHOD: We performed a
      retrospective observational study and included all patients with a diagnosis of
      SE during 2008-2012 at a Swedish tertiary referral centre. RESULTS: The cohort
      consisted of 103 patients (53% female, 47% male, median age 62 years, range 19-87
      years). In house mortality was less than 2 and 70% of the patients' were
      discharged home. The most common aetiologies of SE were uncontrolled epilepsy
      (37%) and brain tumours (16%). A total of 39 patients suffered infections during
      their stay. Presence of infection was associated with mechanical ventilation (OR
      3.344, 95% CI 1.44-7.79) as well as not being discharged home (OR2.705, 95% CI
      1.14-6.44), and duration of SE was significantly longer in patients with
      infection (median 1 day vs. 2.5 days, p<0.001). CONCLUSION: We conclude that the
      previously described association between infections, a longer SE duration, and an
      unfavourable outcome of SE seems valid also in SE of less severe aetiology.

PMID- 24862386
TI  - The accuracy of Goldmann applanation tonometry over silicone hydrogel contact
      lenses in patients with glaucoma.
AB  - PURPOSE: To investigate the accuracy of measuring intraocular pressure over a
      silicone hydrogel contact lens using Goldmann applanation tonometry in eyes with
      glaucoma. METHODS: This was a prospective, randomized study and enrolled 28
      patients (28 right eyes) with primary open angle glaucoma. Intraocular pressure
      was taken with and without a silicone hydrogel contact lens (-0.50 D), in situ
      (using Goldmann applanation tonometry), in a randomized order of measurements.
      Statistical analysis was performed using paired t-test and Bland-Altman plot.
      RESULTS: The mean difference (+/- standard deviation) found between intraocular
      pressure measurement without (mean 16.7 +/- 3.2 mmHg) and with (mean 17.3 +/- 3.0
      mmHg) contact lens was found to be -0.57 +/- 2.3 mmHg (95% confidence interval, 
      1.5 to 0.3). No significant statistical difference was found between the two
      groups with paired t-test (p=0.19). The Bland Altman plot showed some evidence of
      increasing variability of differences between two measures of intraocular
      pressure, with increasing intraocular pressure. The 95% limits of agreement of
      the Bland Altman plot were unacceptably large (-5 mmHg to 3.9 mmHg). CONCLUSION:
      Agreement between Goldmann applanation tonometry with and without contact lenses
      seems to be poor in patients with glaucoma, especially for high intraocular
      pressure.

PMID- 24862387
TI  - All-carbon vertical van der Waals heterostructures: non-destructive
      functionalization of graphene for electronic applications.
AB  - Non-destructive chemical functionalization of graphene for applications in
      electronic devices (e.g., sensors or transducers) is achieved via assembly of
      carbon nanomembrane (CNM)/single-layer graphene (SLG) van der Waals
      heterostructures. The CNMs are 1 nm-thick, dielectric molecular sheets terminated
      with functional amino groups. The structure and performance of heterostructured
      field-effect transistors (FETs) are characterized by photoelectron/Raman
      spectroscopy and by electric transport measurements in vacuum, ambient conditions
      and water. 

PMID- 24862389
TI  - Modulation of brain response to emotional conflict as a function of current mood
      in bipolar disorder: preliminary findings from a follow-up state-based fMRI
      study.
AB  - We used functional magnetic resonance imaging (fMRI) to examine affective control
      longitudinally in a group of patients with bipolar disorder (BD). Participants
      comprised 12 BD patients who underwent repeated fMRI scans in euthymic (n=11),
      depressed (n=9), or hypomanic (n=9) states, and were compared with 12 age-matched
      healthy controls. During fMRI, participants performed an emotional face-word
      interference task with either low or high attentional demands. Relative to
      healthy controls, patients showed decreased activation of the cognitive control
      network normally associated with conflict processing, more severely during
      hypomania than during depression, but regardless of level of task demand in both
      cases. During euthymia, a decreased response to conflict was observed only during
      the high load condition. Additionally, unlike healthy participants, patients
      exhibited deactivation in several key areas in response to emotion-conflict
      trials - including the rostral anterior cingulate cortex during euthymia, the
      hippocampus during depression, and the posterior cingulate cortex during
      hypomania. Our results indicate that the ability of BD patients to recruit
      control networks when processing affective conflict, and the abnormal suppression
      of activity in distinct components of the default mode network, may depend on
      their current clinical state and attentional demand. 

PMID- 24862388
TI  - Cocaine dependent individuals with attenuated striatal activation during
      reinforcement learning are more susceptible to relapse.
AB  - Cocaine-dependent individuals show altered brain activation during decision
      making. It is unclear, however, whether these activation differences are related
      to relapse vulnerability. This study tested the hypothesis that brain-activation
      patterns during reinforcement learning are linked to relapse 1 year later in
      individuals entering treatment for cocaine dependence. Subjects performed a Paper
      Scissors-Rock task during functional magnetic resonance imaging (fMRI). A year
      later, we examined whether subjects had remained abstinent (n=15) or relapsed
      (n=15). Although the groups did not differ on demographic characteristics,
      behavioral performance, or lifetime substance use, abstinent patients reported
      greater motivation to win than relapsed patients. The fMRI results indicated that
      compared with abstinent individuals, relapsed users exhibited lower activation in
      (1) bilateral inferior frontal gyrus and striatum during decision making more
      generally; and (2) bilateral middle frontal gyrus and anterior insula during
      reward contingency learning in particular. Moreover, whereas abstinent patients
      exhibited greater left middle frontal and striatal activation to wins than
      losses, relapsed users did not demonstrate modulation in these regions as a
      function of outcome valence. Thus, individuals at high risk for relapse relative
      to those who are able to abstain allocate fewer neural resources to action
      outcome contingency formation and decision making, as well as having less
      motivation to win on a laboratory-based task. 

PMID- 24862390
TI  - Abnormal relationships between the neural response to high- and low-calorie foods
      and endogenous acylated ghrelin in women with active and weight-recovered
      anorexia nervosa.
AB  - Evidence contributing to the understanding of neurobiological mechanisms
      underlying appetite dysregulation in anorexia nervosa draws heavily on separate
      lines of research into neuroendocrine and neural circuitry functioning. In
      particular, studies consistently cite elevated ghrelin and abnormal activation
      patterns in homeostatic (hypothalamus) and hedonic (striatum, amygdala, insula)
      regions governing appetite. The current preliminary study examined the
      interaction of these systems, based on research demonstrating associations
      between circulating ghrelin levels and activity in these regions in healthy
      individuals. In a cross-sectional design, we studied 13 women with active
      anorexia nervosa (AN), 9 women weight-recovered from AN (AN-WR), and 12 healthy
      weight control women using a food cue functional magnetic resonance imaging
      paradigm, with assessment of fasting levels of acylated ghrelin. Healthy-weight
      control women exhibited significant positive associations between fasting
      acylated ghrelin and activity in the right amygdala, hippocampus, insula, and
      orbitofrontal cortex in response to high-calorie foods, associations which were
      absent in the AN and AN-WR groups. Women with AN-WR demonstrated a negative
      relationship between ghrelin and activity in the left hippocampus in response to
      high-calorie foods, while women with AN showed a positive association between
      ghrelin and activity in the right orbitofrontal cortex in response to low-calorie
      foods. Findings suggest a breakdown in the interaction between ghrelin signaling
      and neural activity in relation to reward responsivity in AN, a phenomenon that
      may be further characterized using pharmacogenetic studies. 

PMID- 24862393
TI  - Editorial comment.

PMID- 24862392
TI  - Laparoscopic radical nephrectomy vs laparoscopic or open partial nephrectomy for
      T1 renal cell carcinoma: comparison of complication rates in elderly patients
      during the initial phase of adoption.
AB  - OBJECTIVE: To assess postoperative complication profiles and 30-day mortality (30
      dM) in older patients undergoing either laparoscopic radical nephrectomy (LRN)
      compared with open partial nephrectomy (OPN) or laparoscopic partial nephrectomy
      (LPN) for early stage renal cell carcinoma. METHODS: Using the Surveillance,
      Epidemiology, and End Results-Medicare linked database, 2277 patients aged>65
      years with T1 renal cell carcinoma, who underwent LRN, OPN, or LPN were
      identified (1992-2005). Surgical and medical complications and 30 dM after
      nephrectomy were abstracted. Bivariate and multivariate logistic regression
      analyses were performed. RESULTS: Relative to LRN, the rate of surgical
      complications was higher for OPN (28% vs 20%; P<.001) and LPN (29% vs 20%;
      P=.01). These differences persisted after multivariate adjustment for patient and
      tumor characteristics (OPN: odds ratio, 1.6; 95% confidence interval, 1.28-1.91;
      P<.001; LPN: odds ratio, 1.6; 95% confidence interval, 1.13-2.39; P=.01).
      Specifically, relative to LRN, OPN was associated with a 7% higher rate of
      genitourinary complications (13% vs 20%; P<.001). Similarly, relative to LRN, LPN
      was associated with a 7% higher rate of genitourinary complications (13% vs 20%;
      P=.001) and with a 4% higher rate of hemorrhagic complications (8% vs 4%; P=.02).
      No statistically significant differences were recorded for all other surgical
      and/or medical complication types and 30 dM (all P>=.2). CONCLUSION: The
      complication and 30-dM rates were not different between LRN, OPN, and LPN groups.
      Exceptions include genitourinary complications that favor LRN relative to OPN and
      LPN and hemorrhagic complications that favor LRN relative to LPN. It is doubtful
      that these results should discourage the use of partial nephrectomy relative to
      LRN in older patients.

PMID- 24862391
TI  - Reduced cortical thickness in veterans exposed to early life trauma.
AB  - Studies have shown that early life trauma may influence neural development and
      increase the risk of developing psychological disorders in adulthood. We used
      magnetic resonance imaging to examine the impact of early life trauma on the
      relationship between current posttraumatic stress disorder (PTSD) symptoms and
      cortical thickness/subcortical volumes in a sample of deployed personnel from
      Operation Enduring Freedom/Operation Iraqi Freedom. A group of 108 service
      members enrolled in the Translational Research Center for Traumatic Brain Injury
      and Stress Disorders (TRACTS) were divided into those with interpersonal early
      life trauma (EL-Trauma+) and Control (without interpersonal early life trauma)
      groups based on the Traumatic Life Events Questionnaire. PTSD symptoms were
      assessed using the Clinician-Administered PTSD Scale. Cortical thickness and
      subcortical volumes were analyzed using the FreeSurfer image analysis package.
      Thickness of the paracentral and posterior cingulate regions was positively
      associated with PTSD severity in the EL-Trauma+ group and negatively in the
      Control group. In the EL-Trauma+ group, both the right amygdala and the left
      hippocampus were positively associated with PTSD severity. This study illustrates
      a possible influence of early life trauma on the vulnerability of specific brain
      regions to stress. Changes in neural morphometry may provide information about
      the emergence and maintenance of symptoms in individuals with PTSD. 

PMID- 24862394
TI  - Reply: To PMID 24862392.

PMID- 24862396
TI  - Editorial comment.

PMID- 24862397
TI  - Reply: To PMID 24862395.

PMID- 24862395
TI  - Prostate Cancer Prevention Trial risk calculator 2.0 for the prediction of low-
      vs high-grade prostate cancer.
AB  - OBJECTIVE: To modify the Prostate Cancer Prevention Trial risk calculator
      (PCPTRC) to predict low- vs high-grade (Gleason grade>=7) prostate cancer and
      incorporate percent free-prostate-specific antigen (PSA). METHODS: Data from 6664
      Prostate Cancer Prevention Trial placebo arm biopsies (5826 individuals), where
      prostate-specific antigen and digital rectal examination results were available
      within 1 year before the biopsy and PSA was <=10 ng/mL, were used to develop a
      nominal logistic regression model to predict the risk of no vs low-grade (Gleason
      grade<7) vs high-grade cancer (Gleason grade>=7). Percent free-PSA was
      incorporated into the model based on likelihood ratio analysis of a San Antonio
      Biomarkers of Risk cohort. Models were externally validated on 10 Prostate Biopsy
      Collaborative Group cohorts and 1 Early Detection Research Network reference set.
      RESULTS: Of all the Prostate Cancer Prevention Trial biopsies, 5468 (82.1%) were
      negative for prostate cancer, 942 (14.1%) detected low-grade, and 254 (3.8%)
      detected high-grade disease. Significant predictors were (log base 2) PSA (odds
      ratio for low-grade vs no cancer, 1.29*; high-grade vs no cancer, 2.02*; high
      grade vs low-grade cancer, 1.57*), digital rectal examination (0.96, 1.49*,
      1.55*, respectively), age (1.02*, 1.05*, 1.03*, respectively), African American
      race (1.13, 2.83*, 2.51*, respectively), prior biopsy (0.63*, 0.81, 1.27,
      respectively), and family history (1.31*, 1.25, 0.95, respectively), where *
      indicates P value<.05. The new PCPTRC 2.0 either with or without percent free-PSA
      (also significant by the likelihood ratio method) validated well externally.
      CONCLUSION: By differentiating the risk of low- vs high-grade disease on biopsy,
      PCPTRC 2.0 better enables physician-patient counseling concerning whether to
      proceed to biopsy.

PMID- 24862398
TI  - Simplified method to measure renal volume: the best correction factor for the
      ellipsoid formula volume calculation in pretransplant computed tomographic live
      donor.
AB  - OBJECTIVE: To find an optimal correction factor that will produce a near-real
      renal volume calculation using the ellipsoid formula. METHODS: We retrospectively
      studied 79 multidetector computed tomography (MDCT) examinations for potential
      renal donor assessment. The renal volumes were calculated using the slice
      summation method, the ellipsoid formula with pi/6 as correction factors as well
      multiple other correction factors for statistical analysis. A paired Student t
      test was used for evaluating the volumes calculated with different correction
      factors and the volumes calculated by the slice summation method. RESULTS: The
      ellipsoid formula using correction factor 0.524 underestimates the renal volume
      by approximately 22.2% with statistical difference compared with the slice
      summation method (P<.05). There is no statistical difference when using
      correction factor in the range of 0.664 to 0.686 (P>.05). Further subgroup
      analysis of gender and laterality was performed and revealed no statistical
      difference. Using a mean value of 0.674 or 0.67 as correction factor results in
      renal volumes that are 100% and 99.5%. CONCLUSION: To avoid underestimation of
      the renal volume by the ellipsoid method, acceptable correction factors are in
      the range of 0.664 to 0.686. We suggest the use of a mean value of 0.674 or 0.67
      as correction factor when using the ellipsoid formula.

PMID- 24862399
TI  - Correlation between lipid profile and heme oxygenase system in patients with
      benign prostatic hyperplasia.
AB  - OBJECTIVE: To investigate the role of heme oxygenase (HO) system in moderate to
      severe benign prostatic hyperplasia and lower urinary tract symptom patients and
      the influence of metabolic syndrome (MetS) components on HO-1 or HO-2 prostatic
      levels. METHODS: One hundred thirty-two consecutive patients who underwent
      transurethral resection of the prostate were prospectively enrolled. MetS was
      defined by the International Diabetes Federation. Patients were divided in 2
      groups: group A (high-density lipoprotein-cholesterol [HDL-C]>=40 mg/dL and
      triglycerides<150 mg/dL) and group B (HDL-C<40 mg/dL and triglycerides>=150
      mg/dL). Surgical specimens were collected for HO level determination. HO-1 levels
      were determined by enzyme-linked immunosorbent assay and HO-1 levels by Western
      blotting. RESULTS: Patients with MetS showed lower levels of HO-1 (5.29 vs 6.28
      ng/mL; P=.04), HO-2 (1.01 vs 1.83 ng/mL; P=.04), phosphorylated activated protein
      kinase (pAMPK; 0.62 vs 1.11 AUI; P<.01), and HO-activity (61.43 vs 70.22 AUI;
      P<.01) with respect to normal. The Pearson correlation analysis showed that HO-1,
      HO-2, and HO activity were negatively associated with waist circumference
      (P<.05), body mass index (P<.05), triglycerides (P<.05) and positively with HDL-C
      (P<.05). Group B showed lower levels of HO-1 (4.7 vs 6.6 ng/mL; P<.05), HO-2 (1.4
      vs 0.4 ng/mL; P=.03), HO-activity (69.63 vs 58.42 AUI; P=.04), and higher
      International Prostate Symptoms Score (21.4 vs 25.0; P<.05) with respect to group
      A. The enzyme-linked immunosorbent assay showed that HO-1 and HO activity levels
      were significantly lower in group B compared with group A. Reduced HDL-C and
      elevated triglyceride levels decreased HO-1 expression in the prostate tissue.
      Western blot analysis of tissue samples showed significant differences in basal
      protein expression levels of HO-2 and pAMPK in group B compared with group A.
      CONCLUSION: Alteration of serum triglycerides and HDL-C significantly impairs HO
      1 and HO-2 levels in benign prostatic hyperplasia patients.

PMID- 24862400
TI  - Human proteins characterization with subcellular localizations.
AB  - Proteins are responsible for performing the vast majority of cellular functions
      which are critical to a cell's survival. The knowledge of the subcellular
      localization of proteins can provide valuable information about their molecular
      functions. Therefore, one of the fundamental goals in cell biology and proteomics
      is to analyze the subcellular localizations and functions of these proteins.
      Recent large-scale human genomics and proteomics studies have made it possible to
      characterize human proteins at a subcellular localization level. In this study,
      according to the annotation in Swiss-Prot, 8842 human proteins were classified
      into seven subcellular localizations. Human proteins in the seven subcellular
      localizations were compared by using topological properties, biological
      properties, codon usage indices, mRNA expression levels, protein complexity and
      physicochemical properties. All these properties were found to be significantly
      different in the seven categories. In addition, based on these properties and
      pseudo-amino acid compositions, a machine learning classifier was built for the
      prediction of protein subcellular localization. The study presented here was an
      attempt to address the aforementioned properties for comparing human proteins of
      different subcellular localizations. We hope our findings presented in this study
      may provide important help for the prediction of protein subcellular localization
      and for understanding the general function of human proteins in cells. 

PMID- 24862401
TI  - The DeAngelis-Beddington functional response and the evolution of timidity of the
      prey.
AB  - We study the evolution of "timidity" of the prey (i.e., its readiness to seek
      refuge) in a predator-prey model with the DeAngelis-Beddington functional
      response. Using the theory of adaptive dynamics, we find that a predator-prey
      population at equilibrium always favours less timidity. Low levels of timidity,
      however, may destabilise the population and lead to cycles. Large-amplitude
      cycles favour a positive level of timidity, but if such cycles do not occur,
      timidity will evolve all the way to zero, where the prey no longer responds to
      the predator by seeking refuge, and in which case the DeAngelis-Beddington
      functional response has become identical to the Holling type-II functional
      response. 

PMID- 24862402
TI  - Enhanced role of eddies in the Arctic marine biological pump.
AB  - The future conditions of Arctic sea ice and marine ecosystems are of interest not
      only to climate scientists, but also to economic and governmental bodies.
      However, the lack of widespread, year-long biogeochemical observations remains an
      obstacle to understanding the complicated variability of the Arctic marine
      biological pump. Here we show an early winter maximum of sinking biogenic flux in
      the western Arctic Ocean and illustrate the importance of shelf-break eddies to
      biological pumping from wide shelves to adjacent deep basins using a combination
      of year-long mooring observations and three-dimensional numerical modelling. The
      sinking flux trapped in the present study included considerable fresh organic
      material with soft tissues and was an order of magnitude larger than previous
      estimates. We predict that further reductions in sea ice will promote the entry
      of Pacific-origin biological species into the Arctic basin and accelerate
      biogeochemical cycles connecting the Arctic and subarctic oceans. 

PMID- 24862403
TI  - Structure of hydrocarbonoclastic nitrate-reducing bacterial communities in
      bioturbated coastal marine sediments.
AB  - The organisation of denitrifying microorganisms in oil-polluted bioturbated
      sediments was investigated in mesocosms under conditions as closer as possible to
      that observed in the environment. Molecular and culture-dependent approaches
      revealed that denitrifying Gammaproteobacteria were abundant in oil-polluted and
      bioturbated sediments suggesting that they may play a key role in hydrocarbon
      degradation in the environment. T-RFLP and gene libraries analyses targeting nirS
      gene showed that denitrifying microbial communities structure was slightly
      affected by either the addition of Hediste diversicolor or crude oil revealing
      the metabolic versatility of denitrifying microorganisms. From oil-polluted
      sediments, distinct denitrifying hydrocarbonoclastic bacterial consortia were
      obtained by enrichment cultures on high molecular weight polyaromatic
      hydrocarbons (PAHs) (dibenzothiophene, fluoranthene, pyrene and chrysene) under
      nitrate-reducing conditions. Interestingly, molecular characterisation of the
      consortia showed that the denitrifying communities obtained from oiled microcosms
      with addition of H. diversicolor were different to that observed without H.
      diversicolor addition, especially with fluoranthene and chrysene revealing the
      bacterial diversity involved in the degradation of these PAHs. 

PMID- 24862404
TI  - Exploring the indirect effects of catechol-O-methyltransferase (COMT) genotype on
      psychotic experiences through cognitive function and anxiety disorders in a large
      birth cohort of children.
AB  - Children reporting psychotic experiences (PEs) are at increased risk of
      developing psychosis in adulthood. Cognitive deficits and anxiety disorders often
      precede psychotic disorders and are associated with higher risk of PEs. While the
      high activity alleles of variants within COMT have been associated with cognitive
      deficits, and the low activity alleles with higher risk of anxiety disorders, no
      associations of COMT with PEs have been found. One possible explanation is that
      the association between COMT and PEs is indirect, through cognitive function and
      anxiety disorders. We examined whether the association between PEs and COMT (four
      single nucleotide polymorphisms and three haplotypes) is indirect, through
      cognition or anxiety disorders. 6,784 individuals from the Avon Longitudinal
      Study of Parents and Children (ALSPAC) were genotyped and completed
      neurocognitive assessments at ages 8 and 11, as well as semi-structured
      interviews for anxiety disorders and PEs at ages 10 and 12, respectively. Alleles
      rs2097603 and rs4680, and two COMT haplotypes, all indexing high activity, were
      indirectly associated with higher risk of PEs through impaired processing speed,
      IQ and attention. There was no evidence of a total effect of COMT on PEs, nor for
      an indirect effect through anxiety disorders. This is the first study to examine
      indirect effects of COMT on PEs. Evidence of an indirect association suggests a
      complex developmental pathway underlies the emergence of PEs in children, with
      possible implications for prevention/intervention strategies. Our findings
      provide additional support for processing speed and attention as endophenotypes
      in psychotic disorders.

PMID- 24862406
TI  - Preparation of well-defined antibody-drug conjugates through glycan remodeling
      and strain-promoted azide-alkyne cycloadditions.
AB  - Antibody-drug conjugates hold considerable promise as anticancer agents, however,
      producing them remains a challenge and there is a need for mild, broadly
      applicable, site-specific conjugation methods that yield homogenous products. It
      was envisaged that enzymatic remodeling of the oligosaccharides of an antibody
      would enable the introduction of reactive groups that can be exploited for the
      site-specific attachment of cytotoxic drugs. This is based on the observation
      that glycosyltransferases often tolerate chemical modifications in their sugar
      nucleotide substrates, thus allowing the installation of reactive
      functionalities. An azide was incorporated because this functional group is
      virtually absent in biological systems and can be reacted by strain-promoted
      alkyne-azide cycloaddition. This method, which does not require genetic
      engineering, was used to produce an anti-CD22 antibody modified with doxorubicin
      to selectively target and kill lymphoma cells. 

PMID- 24862405
TI  - Aging and contribution of MyD88 and TRIF to expression of TLR pathway-associated
      genes following stimulation with Porphyromonas gingivalis.
AB  - BACKGROUND AND OBJECTIVE: Periodontal disease is a highly complex chronic
      inflammatory disease of the oral cavity. Multiple factors influence periodontal
      disease, including socio-economic status, genetics and age; however, inflammation
      elicited by the presence of specific bacteria in the subgingival space is thought
      to drive the majority of soft- and hard-tissue destruction. Porphyromonas
      gingivalis is closely associated with periodontal disease. Toll-like receptors
      (TLRs) and their intracellular signaling pathways play roles in the host response
      to P. gingivalis. The focus of the current study was to use microarray analysis
      to define the contributions of the TLR adaptor molecules myeloid differentiation
      factor 88 (MyD88) and Toll/interleukin-1 receptor domain-containing adaptor
      inducing interferon-beta (TRIF), and aging, on the expression of TLR pathway
      associated mRNAs in response to P. gingivalis. MATERIAL AND METHODS: Bone marrow
      derived macrophages (BMO) from wild-type (Wt), MyD88 knockout (MyD88-KO) and
      Trif(Lps2) [i.e. containing a point mutation in the lipopolysaccharide 2 (Lps2)
      gene rendering the Toll/interleukin (IL)-1 receptor domain-containing adaptor
      inducing interferon-beta (TRIF) protein nonfunctional] mice, at 2-and 12-mo of
      age, were cultured with P. gingivalis. Expression of genes in BMO cultured with
      P. gingivalis was determined in comparison with expression of genes in BMO
      cultured in medium only. RESULTS: Using, as criteria, a twofold increase or
      decrease in mRNA expression, differential expression of 32 genes was observed
      when Wt BMO from 2-mo-old mice were cultured with P. gingivalis compared with the
      medium-only control. When compared with 2-mo-old Wt mice, 21 and 12 genes were
      differentially expressed (p < 0.05) as a result of the mutations in MyD88 or
      TRIF, respectively. The expression of five genes was significantly (p < 0.05)
      reduced in Wt BMO from 12-mo-old mice compared with those from 2-mo-old mice
      following culture with P. gingivalis. Age also influenced the expression of genes
      in MyD88-KO and Trif(Lps2) mice challenged with P. gingivalis. CONCLUSIONS: Our
      results indicate that P. gingivalis induces differential expression of TLR
      pathway-associated genes, and both MyD88 and TRIF play roles in the expression of
      these genes. Age also played a role in the expression of TLR-associated genes
      following stimulation of BMO with P. gingivalis.

PMID- 24862408
TI  - The G-spot does not exist.

PMID- 24862407
TI  - Loss of Sparc in p53-null Astrocytes Promotes Macrophage Activation and
      Phagocytosis Resulting in Decreased Tumor Size and Tumor Cell Survival.
AB  - Both the induction of SPARC expression and the loss of the p53 tumor suppressor
      gene are changes that occur early in glioma development. Both SPARC and p53
      regulate glioma cell survival by inverse effects on apoptotic signaling.
      Therefore, during glioma formation, the upregulation of SPARC may cooperate with
      the loss of p53 to enhance cell survival. This study determined whether the loss
      of Sparc in astrocytes that are null for p53 would result in reduced cell
      survival and tumor formation and increased tumor immunogenicity in an in vivo
      xenograft brain tumor model. In vitro, the loss of Sparc in p53-null astrocytes
      resulted in an increase in cell proliferation, but a loss of tumorigenicity. At 7
      days after intracranial implantation, Sparc-null tumors had decreased tumor cell
      survival, proliferation and reduced tumor size. The loss of Sparc promoted
      microglia/macrophage activation and phagocytosis of tumor cells. Our results
      indicate that the loss of p53 by deletion/mutation in the early stages of glioma
      formation may cooperate with the induction of SPARC to potentiate cancer cell
      survival and escape from immune surveillance. 

PMID- 24862409
TI  - Gardner's syndrome, a rare combination in surgical practice.
AB  - A 45-year-old man presented to the emergency ward with features of intestinal
      obstruction of 2 days duration. On admission, there was abdominal distension and
      multiple sessile polyps found on digital rectal examination. In addition, a soft
      tissue swelling near the elbow and a bony swelling over scalp were noted.
      Abdominal radiography revealed gaseous distension of the small and large bowel,
      and ultrasound revealed diffuse, gas-filled bowel with sluggish peristalsis. The
      obstruction failed to resolve with conservative measures and at emergency
      laparotomy an irregular hard recto-sigmoid junction mass was identified. A
      defunctioning transverse loop colostomy was undertaken and the abdomen closed.
      During recovery, a colonoscopy was performed and a malignant appearing lesion was
      identified 15 cm proximal to the anal verge. Further per-stomal colonoscopy
      revealed multiple sessile polyps from the ileo-caecal valve to the descending
      colon. The cutaneous and abdominal findings were consistent with a rare acute
      presentation of Gardner's syndrome.

PMID- 24862410
TI  - Acute silicosis with bilateral pneumothorax.
AB  - We present a case of acute silicosis with bilateral pneumothorax of a 28-year-old
      man working at a stone crusher factory for 1 year. He presented to the emergency
      department with cough, respiratory distress and diffuse chest pain. The patient
      was managed with bilateral intercostal tube drainage under water seal, oxygen
      inhalation and conservative therapy. On follow-up he showed improvement of
      resting dyspnoea and was doing well. This case is being reported because of the
      rare complications of acute silicosis as bilateral pneumothorax. 

PMID- 24862411
TI  - Vertebral artery thrombosis: a rare presentation of primary polycythaemia.
AB  - Primary polycythaemia, also known as polycythaemia vera (PV), is a
      myeloproliferative neoplasm (MPN) which is associated with arterial and venous
      thrombosis and which can contribute to significant morbidity and mortality if
      untreated. Arterial thrombosis accounts for a large proportion of PV-related
      thrombotic events which may manifest as stroke and myocardial infarction. There
      is an abundance of literature documenting thrombosis arising in the cerebral
      vasculature secondary to PV. However, vertebral artery thrombosis associated with
      PV has not been previously described. We present a case of vertebral artery
      thrombosis as the presenting manifestation of PV. This case demonstrates the
      importance of recognising MPNs as a cause of an unusual presentation of
      thrombosis. 

PMID- 24862412
TI  - Unusual radial nerve injury by a locking compression plate for humerus fracture.
AB  - The management of primary and secondary radial nerve palsy associated with
      humeral shaft fractures is still controversial. Radial nerve function is likely
      to return spontaneously after primary as well as secondary radial nerve palsy in
      the absence of any level of neurotmesis. Identification and protection of the
      radial nerve during surgery may prevent secondary nerve palsy, but is not always
      performed and depends on the location of the fracture, and the experience and
      preference of the surgeon. We report a case of a healthy 40-year-old woman,
      referred to our hospital with a complete radial nerve palsy and a failed plate
      fixation of a right humeral shaft fracture. During exploration of the radial
      nerve and surgical revision of the fracture, we found the nerve entrapped by the
      plate and partially transected by a screw. Full recovery of radial nerve function
      occurred after neurolysis and microscopic neurorrhaphy. 

PMID- 24862413
TI  - Cholecystocutaneous fistula: an unusual complication of a para-umbilical hernia
      repair.
AB  - This case describes a 94-year-old woman who presented 2 years postsutured para
      umbilical hernia repair with a painful black lump protruding through her scar
      with blood stained discharge. This was initially thought to be either ischaemic
      bowel secondary to strangulated incisional hernia or a large organised haematoma.
      An urgent CT scan was performed following which the patient passed two large
      calculi and bile-stained fluid spontaneously through the wound, making the
      diagnosis somewhat clearer. The scan revealed an incisional hernia containing the
      gallbladder and two large calculi at the skin surface and an incidental large
      caecal cancer with surrounding lymphadenopathy. Frail health and the incidental
      finding of a colon cancer rendered invasive surgical management inappropriate.
      Therefore, she was managed conservatively with antibiotics. A catheter was
      inserted into the fistula tract to allow free drainage and alleviate pressure
      related symptoms. The patient was discharged following a multidisciplinary team
      discussion.

PMID- 24862416
TI  - What the mind knows but the eyes may still miss: reducing the 'Acromegalic
      Window'.
AB  - A 46-year-old Asian man was referred to our endocrine unit (April 2013) by his
      general practitioner for investigation of a neck mass. Ultrasound scan of the
      neck and serum thyroid-stimulating hormone levels revealed a euthyroid
      multinodular goitre. He presented with symptoms of frequent headaches,
      polydypsia, polyuria, perspiration and night sweats and demonstrated classic
      physical features of acromegaly. In retrospect, the patient's medical history
      included encounters with numerous physicians from an array of specialties for
      over 20 years, mostly for symptoms well recognised to be attributed to growth
      hormone (GH) excess. Random insulin-like growth factor-1 level was elevated at
      103 nmol/L (normal 13-37 nmol/L) and oral glucose tolerance test showed non
      suppressible GH secretion (15.06 mIU/L at 120 min). MRI revealed a mildly
      enlarged pituitary gland. The patient has been referred for surgery. This case
      highlights that, even with classic features of acromegaly, there may be a wide
      ranging 'Acromegalic Window' between first presentation and clinical suspicion to
      eventual diagnosis.

PMID- 24862414
TI  - Uncontrolled asthma and recurring pulmonary opacities: just asthma?
AB  - In asthma, when comorbidities and common causes of poor control have been
      considered and treated, the clinician may speculate, 'Is it all asthma?'. In
      patients with uncontrolled atopic asthma with recurring episodes of symptoms
      mimicking pneumonia, the suspicion of allergic bronchopulmonary aspergillosis
      (ABPA) should remain high. ABPA is caused by a complex immunological
      hypersensitivity reaction to colonisation with Aspergillus fumigatus in the
      bronchial tree, and is characterised by the presence of atopic asthma, blood
      eosinophilia, migrating pulmonary opacities and potential bronchiectasis. This
      case report describes a delay in diagnosing ABPA which was imitating pneumonia.
      The clinician should pay increased attention to ABPA and test for this in
      patients with uncontrolled asthma with an ongoing requirement for oral
      corticosteroids and/or antibiotics and with pulmonary opacities on chest imaging.

PMID- 24862418
TI  - Spondyloepiphyseal dysplasia tarda with progressive arthropathy associated with
      subcapsular cataract.
AB  - Spondyloepiphyseal dysplasia tarda with progressive arthropathy is a form of
      inherited skeletal dysplasia involving the axial skeleton along with swelling and
      deformities of the peripheral joints that mimics juvenile rheumatoid arthritis.
      We report a case of a 14-year-old school boy who presented with dwarfism, spine
      deformity, ocular anomaly and peripheral arthropathy with characteristic
      radiological changes in the vertebrae and multiple other joints. 

PMID- 24862419
TI  - Sudden worsening after subdural haematoma surgery: will there be a corpus
      callosum injury?
AB  - We report a case of mild encephalopathy with a reversible splenial lesion (MERS)
      which occurred after chronic subdural haematoma (CSDH) surgery. The patient was
      admitted to our hospital for drowsiness and marked asthenia. The cerebral CT scan
      revealed a CSDH and surgery allowed to improve the symptoms, but after several
      days we observed a sudden worsening. The patient developed left-sided myoclonic
      seizures followed by left hemiplegia and worsening drowsiness. Electrolytes
      imbalance and inflammatory causes were excluded. The CT scan showed a right
      cerebral swelling and the subsequent MRI revealed a single lesion in the splenium
      of the corpus callosum, hyperintense on diffusion-weighted images. After osmotic
      therapy the patient improved and on day 10 of admission the MRI showed a complete
      resolution of the lesion. This is the first report that described an association
      between CSDH and MERS. Possible aetiopathogenetic mechanisms are discussed. 

PMID- 24862421
TI  - A rare case of racemose neurocysticercosis of the posterior fossa.
AB  - A 43-year-old man presented with a 3 month history of headache, vertigo and
      swaying while walking. MRI of the brain showed cystic lesions involving the
      cerebellopontine angle cisterns, the right perimedullary cistern, the fourth
      ventricle and bilateral foramen of Luschka with resultant obstruction to
      cerebrospinal fluid outflow and hydrocephalus. The patient underwent right
      retromastoid craniotomy with endoscopic third ventriculostomy for cyst excision.
      The postoperative period was uneventful and he was able to carry out routine
      activities within a month. This case report stresses on the clinical importance,
      unique characteristics and imaging features of racemose neurocysticercosis. 

PMID- 24862423
TI  - Cardiac tamponade in hypothyroidism.

PMID- 24862424
TI  - Symmetrical peripheral gangrene due to Plasmodium falciparum malaria.
AB  - A 45-year-old man presented with a 4-day history of high-grade fever with rigours
      and a 2-day history of painful bluish black discolouration of extremities
      (acrocyanosis). He was haemodynamically stable and all peripheral pulses
      palpable, but the extremities were cold with gangrene involving bilateral fingers
      and toes. Mild splenomegaly was present on abdominal examination but rest of the
      physical examinations were normal. On investigating he was found to have anaemia,
      thrombocytopaenia with gametocytes of Plasmodium falciparum on peripheral blood
      smear. His blood was uncoagulable during performance of prothrombin time with a
      raised D-dimer. Oxygen saturation was normal and the arterial Doppler test showed
      reduced blood flow to the extremities. A diagnosis of complicated P. falciparum
      malaria with disseminated intravascular coagulation (DIC) leading to symmetrical
      peripheral gangrene was performed. Artemisinin combination therapy was started
      and heparin was given for DIC. A final line of demarcation of gangrene started
      forming by 12th day. 

PMID- 24862425
TI  - Single incision laparoscopic surgery for Meckel's diverticulum in an adult.

PMID- 24862426
TI  - Gallbladder torsion with acute cholecystitis and gross necrosis.
AB  - A 92-year-old woman presented to the emergency department with a 2-week history
      of worsening right-sided abdominal pain. On examination she had right mid
      abdominal tenderness. Laboratory studies demonstrated leukocytosis with normal
      liver function tests. A CT of the abdomen was remarkable for a large fluid
      collection in the right abdomen and no discernible gallbladder in the gallbladder
      fossa. An ultrasound confirmed the suspicion of a distended, floating
      gallbladder. The patient was taken to the operating room for laparoscopic
      cholecystectomy. The gallbladder was found to have volvulised in a counter 
      clockwise manner around its pedicle, with gross necrosis of the gallbladder. She
      underwent laparoscopic cholecystectomy. Pathological examination revealed acute
      necrotising calculus cholecystitis. 

PMID- 24862427
TI  - Safe delivery of two parturient women in severe metabolic acidosis.
AB  - Care of an acutely ill parturient is particularly difficult when we have to
      balance the needs of both mother and the fetus to survive. The literature
      suggests there should be emphasis on stabilising the mother's condition. In
      dealing with metabolic acidosis, however, we believe delivering the baby early
      might not only relieve the threat of the acidosis on the mother, it may be the
      only way to deliver a live baby. We report two parturient women with severe
      metabolic acidosis which was considerably reduced very soon after the delivery
      and how our timely delivery resulted in the birth of two neurologically intact
      babies. 

PMID- 24862428
TI  - Forgotten double J stents with a 'Houdini'-like vanishing act.

PMID- 24862431
TI  - Acute type A aortic dissection with cardiac tamponade: unexpected late survival
      without aortic surgery.
AB  - Acute type A aortic dissection complicated by cardiac tamponade portends a lethal
      prognosis. We report the unusual case of an older female who unexpectedly
      survived for more than one year after presentation with acute dissection and
      tamponade. She was treated with a pericardial window and remains alive now four
      years after presentation.

PMID- 24862429
TI  - Thigh fat and muscle each contribute to excess cardiometabolic risk in South
      Asians, independent of visceral adipose tissue.
AB  - OBJECTIVE: To compare fat distribution and associations between fat depots and
      cardiometabolic traits in South Asians and Europeans. METHODS: Five hundred and
      fourteen South Asians and 669 Europeans, aged 56-86. Questionnaires, record
      review, blood testing, and coronary artery calcification scores provided diabetes
      and clinical plus subclinical coronary heart disease (CHD) diagnoses. Abdominal
      visceral (VAT) and subcutaneous adipose tissue, thigh subcutaneous adipose tissue
      (TSAT), intermuscular and intramuscular thigh fat and thigh muscle were measured
      by CT. RESULTS: Accounting for body size, South Asians had greater VAT and TSAT
      than Europeans, but less thigh muscle. Associations between depots and disease
      were stronger in South Asians than Europeans. In multivariable analyses in South
      Asians, VAT was positively associated with diabetes and CHD, while TSAT and thigh
      muscle were protective for diabetes, and thigh muscle for CHD. Differences in VAT
      and thigh muscle only partially explained the excess diabetes and CHD in South
      Asians versus Europeans. Insulin resistance did not account for the effects of
      TSAT or thigh muscle. CONCLUSIONS: Greater VAT and TSAT and lesser thigh muscle
      in South Asians contributed to ethnic differences in cardiometabolic disease.
      Effects of TSAT and thigh muscle were independent of insulin resistance.

PMID- 24862430
TI  - Metformin may produce antidepressant effects through improvement of cognitive
      function among depressed patients with diabetes mellitus.
AB  - Diabetes mellitus and depressive disorders are both common chronic diseases that
      increase functional disability and social burden. Cognitive impairment is a
      potentially debilitating feature of depression. Previous evidence indicates that
      the antidiabetic drug metformin could be suitable for diabetic patients with
      cognitive impairment. However, there is no direct evidence from clinical studies
      that metformin treatment improves cognitive function in diabetic patients
      suffering from depression. In the present study, 58 participants diagnosed with
      depression and type 2 diabetes mellitus (T2DM) were recruited and divided into
      two groups, one treated with metformin and the other treated with placebo for 24
      weeks. Cognitive function, depressive behaviour and diabetes improvement were
      evaluated. Chronic treatment with metformin for 24 weeks improved cognitive
      performance, as assessed by the Wechsler Memory Scale-Revised, in depressed
      patients with T2DM. In addition, metformin significantly improved depressive
      performance and changed the glucose metabolism in depressed patients with
      diabetes. Depressive symptoms were negatively correlated with cognitive
      performance in metformin-treated participants. Furthermore, associations were
      observed between the parameters of blood glucose metabolism and the depression
      phenotype. These findings suggest that chronic treatment with metformin has
      antidepressant behavioural effects and that improved cognitive function is
      involved in the therapeutic outcome of metformin. The results of the present
      study also raise the possibility that supplementary administration of
      antidiabetic medications may enhance the recovery of depression, comorbid with
      T2DM, through improvements in cognitive performance. 

PMID- 24862432
TI  - T-cell receptor gene rearrangement analysis of sequential biopsies in cutaneous T
      cell lymphomas with the Biomed-2 PCR reveals transient T-cell clones in addition
      to the tumor clone.
AB  - Detection of a dominant T-cell clone by T-cell receptor (TCR) gene rearrangement
      analysis is often essential for the diagnosis of cutaneous T-cell lymphomas
      (CTCL). The occurrence of T-cell clones in addition to the diagnostic T-cell
      clone during the course of CTCL has been reported, but the data of these studies
      have been contradictory. We retrospectively evaluated the data of 114 lesional
      skin biopsies from 26 patients with Mycosis fungoides and two patients with
      primary cutaneous anaplastic large cell lymphoma, which were analysed with the
      standardized Biomed-2 PCR for the TCRgamma and TCRbeta locus. A dominant T-cell
      clone was repetitively detected in 93% (26/28) of patients. Additional T-cell
      clones appeared temporarily in 39% (11/28) of patients. Correlation with the
      clinical data did not show an association of the presence of additional T-cell
      clones with age, number of treatments, progression of disease or survival. Our
      findings demonstrate that a persistent T-cell clone, most likely the disease
      causing tumor clone, is detectable in almost all CTCL patients. In addition,
      transiently appearing T-cell clones frequently occur during the course of
      disease. The biological relevance of these additional clones has still to be
      determined. However, it is important to take the possibility of additional T-cell
      clones into account for diagnostic analyses.

PMID- 24862433
TI  - Functionally connected brain regions in the network activated during capsaicin
      inhalation.
AB  - Coughing and the urge-to-cough are important mechanisms that protect the patency
      of the airways, and are coordinated by the brain. Inhaling a noxious substance
      leads to a widely distributed network of responses in the brain that are likely
      to reflect multiple functional processes requisite for perceiving, appraising,
      and behaviorally responding to airway challenge. The broader brain network
      responding to airway challenge likely contains subnetworks that are involved in
      the component functions required for coordinated protective behaviors. Functional
      connectivity analyses were used to determine whether brain responses to airway
      challenge could be differentiated regionally during inhalation of the tussive
      substance capsaicin. Seed regions were defined according to outcomes of previous
      activation studies that identified regional brain responses consistent with cough
      suppression, stimulus intensity coding, and perception of urge-to-cough. The
      subnetworks during continuous inhalation of capsaicin recapitulated the
      distributed regions previously implicated in discrete functional components of
      airway challenge. The outcomes of this study highlight the central representation
      of airways defence as a distributed network.

PMID- 24862434
TI  - Prevention of vertical transmission of hepatitis B: an observational study.
AB  - BACKGROUND: For mothers with chronic hepatitis B virus (HBV) infection, the
      Centers for Disease Control and Prevention recommends immunoprophylaxis to
      decrease perinatal transmission. However, its effectiveness and risk factors for
      failure have not been well-studied in community practice. OBJECTIVE: To
      investigate the effectiveness of a contemporary immunoprophylaxis protocol.
      DESIGN: Observational study. SETTING: An HBV perinatal immunoprophylaxis program
      within Kaiser Permanente Northern California. PATIENTS: 4446 infants born to 3253
      HBV-positive mothers between 1997 and 2010. MEASUREMENTS: Adherence to
      immunoprophylaxis, follow-up testing rates, maternal risk factors for HBV
      transmission, and transmission rates. RESULTS: The infant infection rate was 0.75
      per 100 births from 1997 to 2010 (Poisson 95% CI, 0.48 to 1.10). Rates per 100
      births were 3.37 (CI, 2.08 to 5.14) for e antigen-positive mothers and 0.04 (CI,
      0.001 to 0.24) for e antigen-negative mothers. Among mothers with viral load
      testing, the lowest level associated with transmission was 6.32 * 107 IU/mL.
      Infection rates per 100 births were 3.61 (CI, 0.75 to 10.56) among the 83 births
      to mothers with viral loads of 5 * 107 IU/mL or greater and 0 among the 831
      births to mothers with viral loads less than 5 * 107 IU/mL, regardless of e
      antigen status. LIMITATIONS: Testing for HBV immunity and infection was less
      complete in earlier years. Viral load testing was only consistently available
      starting in 2007. CONCLUSION: Prenatal HBV screening followed by postnatal
      prophylaxis is highly effective in preventing vertical transmission of HBV. A
      negative e antigen status or a viral load less than 5 * 107 IU/mL (90.9% of women
      tested) identifies women at extremely low risk for transmission after
      immunoprophylaxis who are unlikely to benefit from further interventions. PRIMARY
      FUNDING SOURCE: Kaiser Permanente Community Benefit and National Institutes of
      Health.

PMID- 24862435
TI  - Determinants of falls in community-dwelling elderly: hierarchical analysis.
AB  - OBJECTIVE: To analyze the fall-related factors in community-dwelling elderly.
      DESIGN AND SAMPLE: Epidemiologic cross-sectional population-based household study
      with hierarchical interrelationships among the potential risk factors. The sample
      was made up of noninstitutionalized individuals over age 60, who were resident of
      a city in Brazil's Northeast Region. MEASURES: The dependent variable was fall
      occurrence in the last 12 months; independent variables were sociodemographic,
      behavioral, health, and functional status factors. Multivariate hierarchical
      Poisson regression analysis was used based on a proposed theoretic model.
      RESULTS: Three hundred and sixteen (89.0%) elderly participated of the survey,
      average age 74.2 years; the majority was female, with limited literacy and had
      low-medium family income. The fall prevalence was of 25.8%; occurrence was
      related to depression symptoms (PR = 1.55) and balance limitation (PR = 1.56).
      CONCLUSIONS: The high fall prevalence among elderly necessitates the
      identification of fall-related factors for action planning prevention programs
      with this group.

PMID- 24862436
TI  - Hairpin DNA probe-based fluorescence assay for detecting palindrome cleavage
      activity of HIV-1 integrase.
AB  - HIV-1 integrase is a key enzyme for retroviral replication. The integrase can
      perform a palindrome cleavage reaction. In this work, a hairpin DNA probe with a
      palindromic DNA sequence mimicking the HIV-1 LTR-LTR junction of the 2-LTR
      circles in its long stem was designed for fluorescence detection of specific
      restriction-like cleavage activity of HIV-1 integrase. Results showed that the
      designed probe could be recognized and cleaved by HIV-1 integrase. The palindrome
      cleavage reaction can be monitored according to the increase in fluorescent
      signal. The assay can be applied to real-time detection of palindrome cleavage of
      HIV-1 integrase with advantages of simplicity, high sensitivity, and specificity.

PMID- 24862437
TI  - Selective purification of supercoiled p53-encoding pDNA with L-methionine-agarose
      matrix.
AB  - The p53 tumor suppressor gene has been widely explored for gene therapy as an
      alternative to the common treatments. Recently, the supercoiled conformation of a
      p53-encoding plasmid proved to be more efficient in cell transfection and protein
      expression than the open circular conformation. To successfully isolate this
      isoform, several chromatographic techniques have been used, namely affinity
      chromatography with amino acids as ligands. However, the study of new matrices
      and ligands with higher specificity and robustness for supercoiled plasmid
      purification is still required. The present work explores for the first time a
      new matrix of l-methionine-agarose to efficiently purify the supercoiled p53
      encoding plasmid. The binding/elution conditions, such as salt concentration and
      temperature, were manipulated and combined to attain the best strategy.
      Therefore, the supercoiled plasmid isoform was purified from a clarified lysate
      by using a decreasing stepwise gradient comprising 2.35 and 1.7M ammonium sulfate
      in 10mM Tris-HCl, pH 8.0, and finally 10mM Tris-HCl, pH 8.0, at 5 degrees C.
      After accomplishing the purification process, we performed several tests to
      assess the quality of the supercoiled plasmid, revealing that the amounts of
      proteins, gDNA, RNA, and endotoxins were significantly reduced or undetectable in
      the final formulation. 

PMID- 24862438
TI  - Continuous fluorescence-based measurement of redox-driven sodium ion
      translocation.
AB  - Investigation of the mechanism of sodium ion pumping enzymes requires methods to
      follow the translocation of sodium ions by the purified and reconstituted
      proteins in vitro. Here, we describe a protocol that allows following the
      accumulation of Na(+) in proteoliposomes by the Na(+)-translocating NADH:quinone
      oxidoreductase (Na(+)-NQR) from Vibrio cholerae using the sodium-sensitive
      fluorophor sodium green. In the presence of a regenerative system for its
      substrate NADH, the Na(+)-NQR accumulates Na(+) in the proteoliposomes which is
      visible as a change in fluorescence. 

PMID- 24862439
TI  - Different haematological picture of congenital sideroblastic anaemia in a
      hemizygote and a heterozygote.

PMID- 24862440
TI  - Self-healing hybrid nanocomposites consisting of bisphosphonated hyaluronan and
      calcium phosphate nanoparticles.
AB  - Non-covalent interactions are often regarded as insufficient to construct
      macroscopic materials of substantial integrity and cohesion. However, the low
      binding energy of such reversible interactions can be compensated by increasing
      their number to work in concert to create strong materials. Here we present the
      successful development of an injectable, cohesive nanocomposite hydrogel based on
      reversible bonds between calcium phosphate nanoparticles and bisphosphonate
      functionalized hyaluronic acid. These nanocomposites display a capacity for self
      healing as well as adhesiveness to mineral surfaces such as enamel and
      hydroxyapatite. Most importantly, these non-covalently cross-linked composites
      are surprisingly robust yet biodegradable upon extensive in vitro and in vivo
      testing and show bone interactive capacity evidenced by bone ingrowth into
      material remnants. The herein presented method provides a new methodology for
      constructing nanoscale composites for biomedical applications, which owe their
      integrity to reversible bonds.

PMID- 24862442
TI  - Kidney-specific drug delivery system for renal fibrosis based on coordination
      driven assembly of catechol-derived chitosan.
AB  - Renal fibrosis is a common progressive kidney disease, and there is a lack of
      efficient treatment for the condition. In this study, we designed a kidney
      specific nanocomplex by forming coordination-driven assembly from catechol
      derived low molecular weight chitosan (HCA-Chi), metal ions and active drug
      molecules. The coordination activities of various metals and ligands,
      cytotoxicity, immunogenicity and biodistribution of HCA-Chi were investigated.
      Autofluorescent doxorubicin (DOX) was selected to fabricate HCA-Chi-Cu-DOX
      ternary nanocomplex for investigating cellular uptake behavior, transmembrane and
      targeting properties. The nanodevice demonstrated satisfactory stability under
      normal physiological conditions and pH-responsive drug release in acidic
      environments. Uptake of HCA-Chi-Cu-DOX by HK-2 cells was dependent on exposure
      time, concentration, and temperature, and was inhibited by blockers of megalin
      receptor. Tissue distribution showed that HCA-Chi-Cu-DOX nanocomplex was
      specifically accumulated in kidney with a renal relative uptake rate (r(e)) of
      25.6. When active anti-fibrosis compound emodin was installed in HCA-Chi-Zn
      emodin and intravenously injected to the ureter obstructed mice, obvious
      attenuation of fibrotic progression was exhibited. It was concluded that HCA-Chi
      coordination-driven nanocomplex showed special renal targeting capacity and could
      be utilized to develop drug delivery systems for treating renal fibrosis.

PMID- 24862441
TI  - Comparison of biomaterial delivery vehicles for improving acute retention of stem
      cells in the infarcted heart.
AB  - Cell delivery to the infarcted heart has emerged as a promising therapy, but is
      limited by very low acute retention and engraftment of cells. The objective of
      this study was to compare a panel of biomaterials to evaluate if acute retention
      can be improved with a biomaterial carrier. Cells were quantified post
      implantation in a rat myocardial infarct model in five groups (n = 7-8); saline
      injection (current clinical standard), two injectable hydrogels (alginate,
      chitosan/beta-glycerophosphate (chitosan/beta-GP)) and two epicardial patches
      (alginate, collagen). Human mesenchymal stem cells (hMSCs) were delivered to the
      infarct border zone with each biomaterial. At 24 h, retained cells were
      quantified by fluorescence. All biomaterials produced superior fluorescence to
      saline control, with approximately 8- and 14-fold increases with alginate and
      chitosan/beta-GP injectables, and 47 and 59-fold increases achieved with collagen
      and alginate patches, respectively. Immunohistochemical analysis qualitatively
      confirmed these findings. All four biomaterials retained 50-60% of cells that
      were present immediately following transplantation, compared to 10% for the
      saline control. In conclusion, all four biomaterials were demonstrated to more
      efficiently deliver and retain cells when compared to a saline control.
      Biomaterial-based delivery approaches show promise for future development of
      efficient in vivo delivery techniques.

PMID- 24862443
TI  - Stimulation of bone growth following zinc incorporation into biomaterials.
AB  - Rapid development of zinc biology has broadened the applications of Zn
      incorporated biomaterials to tissue engineering but also raised concerns about
      the long-term safety of released Zn(2+) ions. Clinical success hinges on the
      amount of incorporated zinc and subsequent optimized release sufficient to
      stimulate osseointegration. In this study, zinc is incorporated into the sub
      surface of TiO2 coatings by plasma immersion ion implantation and deposition
      (PIII&D). The Zn-implanted coatings show significant improvement compared to the
      "bulk-doped" coatings prepared by plasma electrolyte oxidation in terms of
      osteogenesis in vitro and in vivo. Molecular and cellular osteogenic activities
      demonstrate that rBMSCs cultured on the Zn-implanted coatings have higher ALP
      activity and up-regulated osteogenic-related genes (OCN, Col-I, ALP, Runx2)
      compared to the bulk-doped Zn coatings and controls. In vivo osseointegration
      studies conducted for 12 weeks on the rat model show early-stage new bone
      formation and the bone contact ratio (12 week) on the Zn-implanted coating is
      larger. The ZnT1 and ZIP1 gene expression studies demonstrate that the Zn
      implanted coatings can better stimulate bone growth with reduced Zn release than
      those doped with zinc throughout the coatings.

PMID- 24862445
TI  - Coalescence in concentrated Pickering emulsions under shear.
AB  - We have investigated the rheology of concentrated oil-in-water emulsions
      stabilised by silanised silica nanoparticles. The emulsions behave like highly
      elastic solids in response to small, uniform strains. They become unstable and
      begin to break down, however, on yielding. We show that the emulsion elasticity
      is correlated with the salt concentration in the water and hence the particle
      aggregation in emulsions at a given drop volume fraction. A supporting
      observation is that destabilisation is favoured by minimising the attractive
      interactions between the particles. Microscopic observations revealed that
      coalesced drops have anisotropic shapes and wrinkled surfaces, direct evidence of
      the interfacial particle layer acting like a mechanical barrier to bulk emulsion
      destabilisation. 

PMID- 24862444
TI  - Noninvasive assessment of mitochondrial organization in three-dimensional tissues
      reveals changes associated with cancer development.
AB  - Mitochondrial organization is often altered to accommodate cellular bioenergetic
      and biosynthetic demands. Changes in metabolism are a hallmark of a number of
      diseases, including cancer; however, the interdependence between mitochondrial
      metabolic function and organization is not well understood. Here, we present a
      noninvasive, automated and quantitative method to assess mitochondrial
      organization in three-dimensional (3D) tissues using exclusively endogenous two
      photon excited fluorescence (TPEF) and show that mitochondrial organization
      reflects alterations in metabolic activities. Specifically, we examine the
      organization of mitochondria within live, engineered epithelial tissue
      equivalents that mimic normal and precancerous human squamous epithelial tissues.
      We identify unique patterns of mitochondrial organization in the different tissue
      models we examine, and we attribute these to differences in the metabolic
      profiles of these tissues. We find that mitochondria are clustered in tissues
      with high levels of glycolysis and are more highly networked in tissues where
      oxidative phosphorylation is more dominant. The most highly networked
      organization is observed within cells with high levels of glutamine consumption.
      Furthermore, we demonstrate that mitochondrial organization provides
      complementary information to traditional morphological hallmarks of cancer
      development, including variations in nuclear size. Finally, we present evidence
      that this automated quantitative analysis of endogenous TPEF images can identify
      differences in the mitochondrial organization of freshly excised normal and pre
      cancerous human cervical tissue specimens. Thus, this method could be a promising
      new modality to assess the role of mitochondrial organization in the metabolic
      activity of 3D tissues and could be further developed to serve as an early cancer
      clinical diagnostic biomarker. 

PMID- 24862446
TI  - Bioaccumulation and effects of different-shaped copper oxide nanoparticles in the
      deposit-feeding snail Potamopyrgus antipodarum.
AB  - Copper oxide (CuO) nanoparticles (NPs) are among the most widely used engineered
      NPs and are thus likely to end up in the environment, predominantly in sediments.
      Copper oxide NPs have been found to be toxic to a variety of (mainly pelagic)
      organisms, but to differing degrees. In the present study, the influence of CuO
      NP shape on bioavailability and toxicity in the sediment-dwelling freshwater
      gastropod Potamopyrgus antipodarum was examined. In 2 separate studies, snails
      were exposed to either clean sediment or sediment spiked with either aqueous Cu
      or CuO NPs of different shapes (rods, spheres, or platelets) at 240 ug Cu/g dry
      weight of sediment (nominal). In neither of the studies was survival found to be
      related to Cu form (i.e., free ion vs particle) or shape, whereas snail growth
      was severely influenced by both form and shape. Reproduction was affected (by CuO
      NP spheres and aqueous Cu) only when estimated as the total number (live plus
      dead) of juveniles produced per snail per week. Both the aqueous and particulate
      forms of Cu were available for uptake by snails when mixed into sediment.
      However, Cu body burden was not directly related to observed effects. The present
      study stresses the need for both a better understanding of uptake mechanisms and
      internal distribution pathways of NPs and an assessment of long-term consequences
      of NP exposure.

PMID- 24862447
TI  - Faulting of rocks in a three-dimensional stress field by micro-anticracks.
AB  - Nucleation and propagation of a shear fault is known to be the result of
      interaction and coalescence of many microcracks. Yet the character and rate of
      the microcracks' interactions, and their dependence on the three-dimensional
      stress state are poorly understood. Here we investigate formation of microcracks
      during sandstone faulting under 3D-polyaxial stress fields by analyzing multi
      stationary acoustic waveforms. We show that in a true three-dimensional stress
      state (a) faulting forms in a orthorhombic pattern, and (b) the emitted acoustic
      waveforms from microcracking carry a shorter rapid slip phase. The later is
      associated with microcracking that dominantly develops parallel to the minimum
      stress direction. Our results imply that due to inducing the micro-anticracks,
      the three-dimensional (3D) stress state can quicken dynamic weakening and rupture
      propagation by a factor of two relatively to simpler stress states. The results
      suggest a new nucleation mechanism of 3D-faulting with implications for
      earthquakes' instabilities, as well as the understanding of avalanches associated
      with dislocations. 

PMID- 24862449
TI  - Inhibition of glycogen synthase kinase 3 ameliorates liver ischemia/reperfusion
      injury via an energy-dependent mitochondrial mechanism.
AB  - BACKGROUND & AIMS: The mechanisms of glycogen synthase kinase-3 (GSK-3)-mediated
      cytoprotection during liver ischemia/reperfusion (I/R) remain controversial,
      particularly in older organs. This study explores the role and potential
      mechanisms of GSK-3 in young and aging livers. METHODS: A rodent partial warm I/R
      model was used to evaluate the therapeutic potential of GSK-3 modulation during
      hepatic I/R in young and aging Sprague-Dawley rats. RESULTS: GSK-3 inhibition
      through IPC or SB216763 (SB21) preconditioning protected young rats from I/R
      induced liver injury. This protection was absent in old animals but could be
      restored by glucose infusion prior to the I/R insult. The protection conferred by
      GSK-3 inhibition depended on mitochondrial metabolism regulation. Indeed, the
      inhibition of GSK-3 suppressed mitochondrial permeability transition pore (MPTP)
      opening, triggering mitohormesis in young animals, whereas insufficient fuel
      suppressed mitochondrial metabolism and inactivated the GSK-3-related protection
      in old animals. SB21 and glucose reactivated the mitochondrial F0F1-ATPase and
      subsequent protective cascades in the senescent liver. These effects were
      antagonized by an ATPase inhibitor and by an MPTP opener. CONCLUSIONS: The
      protection conferred by GSK-3 inhibition during hepatic I/R insult is energy
      dependent, particularly in senescent livers. These findings demonstrate a key
      role for GSK-3-related mitochondrial energy homeostasis, which may shed new light
      on the clinical use of GSK-3 inhibitors to protect liver function in surgical
      settings, particularly for older patients.

PMID- 24862448
TI  - Telomerase activated thymidine analogue pro-drug is a new molecule targeting
      hepatocellular carcinoma.
AB  - BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is one of the most common
      malignancies worldwide. Although hepatectomy and transplantation have
      significantly improved survival, there is no effective chemotherapeutic treatment
      for HCC and its prognosis remains poor. Sustained activation of telomerase is
      essential for the growth and progression of HCC, suggesting that telomerase is a
      rational target for HCC therapy. Therefore, we developed a thymidine analogue pro
      drug, acycloguanosyl-5'-thymidyltriphosphate (ACV-TP-T), which is specifically
      activated by telomerase in HCC cells and investigated its anti-tumour efficacy.
      METHODS: First, we verified in vitro whether ACV-TP-T was a telomerase substrate.
      Second, we evaluated proliferation and apoptosis in murine (Hepa1-6) and human
      (Hep3B, HuH7, HepG2) hepatic cancer cells treated with ACV-TP-T. Next, we tested
      the in vivo treatment efficacy in HBV transgenic mice that spontaneously develop
      hepatic tumours, and in a syngeneic orthotopic murine model where HCC cells were
      implanted directly in the liver. RESULTS: In vitro characterization provided
      direct evidence that the pro-drug was actively metabolized in liver cancer cells
      by telomerase to release the active form of acyclovir. Alterations in cell cycle
      and apoptosis were observed following in vitro treatment with ACV-TP-T. In the
      transgenic and orthotopic mouse models, treatment with ACV-TP-T reduced tumour
      growth, increased apoptosis, and reduced the proliferation of tumour cells.
      CONCLUSIONS: ACV-TP-T is activated by telomerase in HCC cells and releases active
      acyclovir that reduces proliferation and induces apoptosis in human and murine
      liver cancer cells. This pro-drug holds a great promise for the treatment of HCC.

PMID- 24862451
TI  - Transparent thin shield for radio frequency transmit coils.
AB  - OBJECTIVE: To identify a shielding material compatible with optical head-motion
      tracking for prospective motion correction and which minimizes radio frequency
      (RF) radiation losses at 7 T without sacrificing line-of-sight to an imaging
      target. MATERIALS AND METHODS: We evaluated a polyamide mesh coated with silver.
      The thickness of the coating was approximated from the composition ratio provided
      by the material vendor and validated by an estimate derived from electrical
      conductivity and light transmission measurements. The performance of the shield
      is compared to a split-copper shield in the context of a four-channel transmit
      only loop array. RESULTS: The mesh contains less than a skin-depth of silver
      coating (300 MHz) and attenuates light by 15 %. Elements of the array vary less
      in the presence of the mesh shield as compared to the split-copper shield
      indicating that the array behaves more symmetrically with the mesh shield. No
      degradation of transmit efficiency was observed for the mesh as compared to the
      split-copper shield. CONCLUSION: We present a shield compatible with future
      integration of camera-based motion-tracking systems. Based on transmit
      performance and eddy-current evaluations the mesh shield is appropriate for use
      at 7 T.

PMID- 24862450
TI  - Assessment of antioxidant and antiproliferative properties of spinach plants
      grown under low oxygen availability.
AB  - BACKGROUND: In the human diet, the consumption of fresh fruits and vegetables is
      important in maintaining good health and in preventing chronic diseases. It is
      known that plant-derived food is a powerful source of chemopreventive molecules,
      i.e. antioxidants, and spinach (Spinacia oleracea L., Chenopodiaceae) possesses a
      wide range of metabolites with such biological activity. Plant stress response
      could lead to the production of metabolites with high value for human health and
      this could be a tool to enhance the production of molecules with antioxidant
      activity in plants. RESULTS: Data reported in this paper confirm the antioxidant
      properties of spinach plants, and show a strong antiproliferative activity of
      leaf extract on HT-29 human cell line. Besides, the hypoxic stress seems to
      affect the pool of antioxidant molecules present in spinach leaves, as verified
      by means of HPLC-MS/MS analysis and the aluminium chloride and ABTS assays.
      CONCLUSION: Our findings represent a basis for improving the biological and
      pharmacological properties of spinach plants, including the use of different
      growth conditions to modulate the phytocomplex profile of spinach.

PMID- 24862452
TI  - The rice gene OsZFP6 functions in multiple stress tolerance responses in yeast
      and Arabidopsis.
AB  - The role of zinc finger proteins in organismal stress conditions has been widely
      reported. However, little is known concerning the function of CCHC-type zinc
      finger proteins in rice. In this study, OsZFP6, a rice CCHC-type zinc finger
      protein 6 gene, was cloned from rice using RT-PCR. The OsZFP6 protein contains
      305 amino acids and a conserved zinc finger domain and is localised to the
      nucleus. Southern blot analysis revealed that a single copy was encoded in the
      rice genome. OsZFP6 expression was increased by abiotic stress, including salt
      (NaCl), alkali (NaHCO3) and H2O2 treatment. When OsZFP6 was transformed into
      yeast, the transgenic yeast showed significantly increased resistance to NaHCO3
      compared to the control. Moreover, Arabidopsis transgenic plants overexpressing
      OsZFP6 were more tolerant to both NaHCO3 and H2O2 treatments. Overall, we
      uncovered a role for OsZFP6 in abiotic stress responses and identified OsZFP6 as
      a putatively useful gene for developing crops with increased alkali and H2O2
      tolerance. 

PMID- 24862453
TI  - Estradiol regulates responsiveness of the dorsal premammillary nucleus of the
      hypothalamus and affects fear- and anxiety-like behaviors in female rats.
AB  - Research suggests a causal link between estrogens and mood. Here, we began by
      examining the effects of estradiol (E2 ) on rat innate and conditioned defensive
      behaviors in response to cat odor. Second, we utilized whole-cell patch clamp
      electrophysiological techniques to assess noradrenergic effects on neurons within
      the dorsal premammillary nucleus of the hypothalamus (PMd), a nucleus implicated
      in fear reactivity, and their regulation by E2 . Our results show that E2
      increased general arousal and modified innate defensive reactivity to cat odor.
      When ovariectomized females treated with E2 as opposed to oil were exposed to cat
      odor, they showed elevations in risk assessment and reductions in freezing,
      indicating a shift from passive to active coping. In addition, animals previously
      exposed to cat odor showed clear cue + context conditioning 24 h later. However,
      although E2 persisted in its effects on general arousal in the conditioning task,
      its effects on fear disappeared. In the patch clamp experiments noradrenergic
      compounds that typically induce fear clearly excited PMd neurons, producing
      depolarizations and action potentials. E2 treatment shifted some excitatory
      effects of noradrenergic agonists to inhibitory, possibly by differentially
      affecting alpha- and beta-adrenoreceptors. In summary, our results implicate E2
      in general arousal and fear reactivity, and suggest these may be governed by
      changes in noradrenergic responsivity in the PMd. These effects of E2 may have
      ethological relevance, serving to promote mate seeking even in contexts of
      ambiguous threat and shed light on the involvement of estrogen in mood and its
      associated disorders. 

PMID- 24862454
TI  - Spinal nerve composition and innervation of the axillary nerve.
AB  - INTRODUCTION: The purpose of this study was to evaluate the spinal nerve
      composition of the axillary nerve and the contribution of each spinal nerve.
      METHODS: Thirty brachial plexi extracted from Korean adults (15 men, 14 women, 1
      unknown; left side, 13; right side, 17) were examined in this study. RESULTS: The
      frequency of the contribution of C4 was 13.3%, and it was mainly innervated the
      deltoid and teres minor muscles. The frequency of inclusion of C7 was 20.0%. C7
      fibers were mainly involved in the deltoid and cutaneous branches. The axillary
      nerve was primarily composed of fibers from C5 and C6 in 66.6%; C4, C5, and C6 in
      13.3%; and C5, C6, and C7 in 20.0%. CONCLUSIONS: These findings may be helpful to
      diagnose damage to axillary nerve structures that occur in such injuries as
      humerus fractures.

PMID- 24862455
TI  - Flavylium network of chemical reactions in confined media: modulation of 3',4',7
      trihydroxyflavilium reactions by host-guest interactions with cucurbit[7]uril.
AB  - In moderately acidic aqueous solutions, flavylium compounds undergo a pH-, and in
      some cases, light-dependent array of reversible chemical reactions. This network
      can be described as a single acid-base reaction involving a flavylium cation
      (acidic form) and a mixture of basic forms (quinoidal base, hemiketal and cis and
      trans chalcones). The apparent pK'a of the system and the relative mole fractions
      of the basic forms can be modulated by the interaction with cucurbit[7]uril. The
      system is studied by using (1) H NMR spectroscopy, UV/Vis spectroscopy, flash
      photolysis, and steady-state irradiation. Of all the network species, the
      flavylium cation possesses the highest affinity for cucurbit[7]uril. The rate of
      interconversion between flavylium cation and the basic species (where trans
      chalcone is dominant) is approximately nine times lower inside the
      cucurbit[7]uril. 

PMID- 24862456
TI  - A single-center experience of cytomegalovirus infections in Asian pediatric
      patients undergoing allogeneic hematopoietic stem cell transplant for leukemia in
      Singapore.
AB  - INTRODUCTION: Cytomegalovirus (CMV) infection remains a significant cause of
      morbidity and mortality in pediatric patients undergoing allogeneic hematopoietic
      stem cell transplantation (HSCT) despite improved surveillance and the current
      preemptive approach. Few data on its prevalence in the Asian pediatric population
      exist. METHODS: We retrospectively reviewed the prevalence of CMV infections in
      33 patients with 37 transplants who received HSCT for leukemia from 1998 to 2008,
      and who were managed preemptively for infections. RESULTS: In the 37 transplants,
      16 patients (43%) had CMV DNAemia. Of the patients who were CMV seropositive
      before transplant and received stem cells from seropositive donors (R+/D+), 69%
      had DNAemia; of those who received stem cells from seronegative donors (R+/D-),
      36% had CMV DNAemia. Of the patients who were CMV naive before transplant and
      received stem cells from seropositive donors (R-/D+), 25% had CMV DNAemia. In CMV
      seronegative donor-recipient transplants (R-/D-), 20% of patients had CMV
      DNAemia. The median time to the first episode of CMV DNAemia was 21 (range: 10
      107) days after the transplants, and the median duration of CMV DNAemia was 22
      (range: 2-315) days. CMV DNAemia recurred in 44% (7 of 16) of these patients.
      Only 1 patient developed CMV disease (retinitis). No deaths were related to CMV
      infections. CONCLUSIONS: CMV infection manifesting as DNAemia is a common
      complication in pediatric patients undergoing allogeneic HSCT for leukemia. Pre
      transplant serostatus predicts reactivation risks; invasive CMV disease is rare
      using the preemptive approach in our patient population.

PMID- 24862457
TI  - Dissemination of bacterial fluoroquinolone resistance in two multidrug-resistant
      enterobacteriaceae.
AB  - Bacterial resistance to antimicrobials has become one of the greatest challenges
      for clinical microbiologists and healthcare practitioners worldwide. Acquisition
      of resistance genes has proven to be difficult to characterize and is largely
      uncontrollable in the environment. Here we sought to characterize conjugal
      horizontal gene transfer of plasmid-encoded fluoroquinolone resistance genes from
      two strains of Enterobacteriaceae, one clinical and one from a municipal
      wastewater treatment plant environment. Conjugation was dissimilar between the
      two strains. Escherichia coli strain LR09, containing a plasmid with the aac(6')
      Ib-cr fluoroquinolone resistance gene, did not conjugate with any of the 15
      strains tested, while Enterobacter aerogenes strain YS11 conjugated with two
      strains of E. coli. The resultant transconjugants were also dissimilar in their
      stability and potential persistence. The observations presented herein exemplify
      the difficulties in understanding and controlling the spread of antimicrobial
      resistance. Thus, it may be prudent to address drug disposal and destruction,
      incorporating a life-cycle assessment plan 'from cradle to grave', treating
      antimicrobials as chemical or environmental contaminants.

PMID- 24862458
TI  - Midazolam and atropine alter theta oscillations in the hippocampal CA1 region by
      modulating both the somatic and distal dendritic dipoles.
AB  - Theta (4-12 Hz) oscillations in the hippocampus play an important role in
      learning and memory. They are altered by a wide variety of drugs that impair
      memory, and these effects may underlie or contribute to drug-induced amnesia.
      However, the network mechanisms linking drug actions with changes in memory
      formation remain poorly defined. Here, we used a multisite linear electrode array
      to measure local field potentials simultaneously across the CA1 layers of the
      hippocampus during active exploration, and employed current source density
      analysis and computational modeling to investigate how midazolam and atropine-two
      amnestic drugs that are used clinically and experimentally-change the relative
      timing and strength of the drivers of theta-oscillations. We found that two
      dipoles are present, with active inputs that are centered at the soma and the
      distal apical dendrite and passive return pathways that overlap in the mid-apical
      dendrite. Both drugs shifted the position of the phase reversal in the local
      field potential that occurred in the mid-apical dendritic region, but in opposite
      directions, by changing the strength of the dendritic pole, without altering the
      somatic pole or relative timing. Computational modeling showed that this
      constellation of changes, as well as an additional effect on a variably present
      mid-apical pole, could be produced by simultaneous changes in the active somatic
      and distal dendritic inputs. These network-level changes, produced by two
      amnestic drugs that target different types of receptors, may thus serve as a
      common basis for impaired memory encoding.

PMID- 24862460
TI  - Autoimmune thyroiditis and isotretinoin: real association or coincidence?

PMID- 24862459
TI  - eHealth interventions for HIV prevention in high-risk men who have sex with men:
      a systematic review.
AB  - BACKGROUND: While the human immunodeficiency virus (HIV) incidence rate has
      remained steady in most groups, the overall incidence of HIV among men who have
      sex with men (MSM) has been steadily increasing in the United States. eHealth is
      a platform for health behavior change interventions and provides new
      opportunities for the delivery of HIV prevention messages. OBJECTIVE: The purpose
      of this systematic review was to examine the use of eHealth interventions for HIV
      prevention in high-risk MSM. METHODS: We systematically searched PubMed, OVID,
      ISI Web of Knowledge, Google Scholar, and Google for articles and grey literature
      reporting the original results of any studies related to HIV prevention in MSM
      and developed a standard data collection form to extract information on study
      characteristics and outcome data. RESULTS: In total, 13 articles met the
      inclusion criteria, of which five articles targeted HIV testing behaviors and
      eight focused on decreasing HIV risk behaviors. Interventions included Web-based
      education modules, text messaging (SMS, short message service), chat rooms, and
      social networking. The methodological quality of articles ranged from 49.4-94.6%.
      Wide variation in the interventions meant synthesis of the results using meta
      analysis would not be appropriate. CONCLUSIONS: This review shows evidence that
      eHealth for HIV prevention in high-risk MSM has the potential to be effective in
      the short term for reducing HIV risk behaviors and increasing testing rates.
      Given that many of these studies were short term and had other limitations, but
      showed strong preliminary evidence of improving outcomes, additional work needs
      to rigorously assess the use of eHealth strategies for HIV prevention in high
      risk MSM.

PMID- 24862463
TI  - Unbalanced translocation der(7)t(7q;11q): a new recurrent aberration leading to
      partial monosomy 7q and trisomy 11q in acute myeloid leukemia.

PMID- 24862462
TI  - Combined occurrence of a novel TOR1A and a THAP1 mutation in primary dystonia.
AB  - BACKGROUND: The DeltaGAG deletion of the TOR1A gene (DYT1) is responsible for
      DYT1 dystonia. However, no other TOR1A mutation has been reported in the Chinese
      population. METHODS: Two hundred one dystonia patients without the DeltaGAG
      deletion were screened for other mutations in TOR1A. Gene function changes were
      analyzed by subcellular distribution and luciferase reporter assay. RESULTS: A
      novel TOR1A mutation (c.581A>T, p.Asp194Val) was found in a patient with early
      onset segmental dystonia harboring a THAP1 mutation (c.539T>C, p.Leu180Ser).
      Overexpression of mutant TOR1A Asp194Val protein induces inclusion formation in
      SK-N-AS cell lines, and the repressive activity of the mutant THAP1 Leu180Ser
      protein on TOR1A gene expression is decreased compared with wild-type THAP1.
      CONCLUSIONS: This is the first report about a dystonia patient harboring two
      distinct dystonia gene mutations. Functional analysis indicated a potential
      additive effect of these two mutations, which might provoke the occurrence of
      dystonic symptoms in this patient.

PMID- 24862461
TI  - Relationship between the functional status scale and the pediatric overall
      performance category and pediatric cerebral performance category scales.
AB  - IMPORTANCE: Functional status assessment methods are important as outcome
      measures for pediatric critical care studies. OBJECTIVE: To investigate the
      relationships between the 2 functional status assessment methods appropriate for
      large-sample studies, the Functional Status Scale (FSS) and the Pediatric Overall
      Performance Category and Pediatric Cerebral Performance Category (POPC/PCPC)
      scales. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study with random
      patient selection at 7 sites and 8 children's hospitals with general/medical and
      cardiac/cardiovascular pediatric intensive care units (PICUs) in the
      Collaborative Pediatric Critical Care Research Network. Participants included all
      PICU patients younger than 18 years. MAIN OUTCOMES AND MEASURES: Functional
      Status Scale and POPC/PCPC scores determined at PICU admission (baseline) and
      PICU discharge. We investigated the association between the baseline and PICU
      discharge POPC/PCPC scores and the baseline and PICU discharge FSS scores, the
      dispersion of FSS scores within each of the POPC/PCPC ratings, and the
      relationship between the FSS neurologic components (FSS-CNS) and the PCPC.
      RESULTS: We included 5017 patients. We found a significant (P < .001) difference
      between FSS scores in each POPC or PCPC interval, with an FSS score increase with
      each worsening POPC/PCPC rating. The FSS scores for the good and mild disability
      POPC/PCPC ratings were similar and increased by 2 to 3 points for the POPC/PCPC
      change from mild to moderate disability, 5 to 6 points for moderate to severe
      disability, and 8 to 9 points for severe disability to vegetative state or coma.
      The dispersion of FSS scores within each POPC and PCPC rating was substantial and
      increased with worsening POPC and PCPC scores. We also found a significant (P <
      .001) difference between the FSS-CNS scores between each of the PCPC ratings with
      increases in the FSS-CNS score for each higher PCPC rating. CONCLUSIONS AND
      RELEVANCE: The FSS and POPC/PCPC system are closely associated. Increases in FSS
      scores occur with each higher POPC and PCPC rating and with greater magnitudes of
      change as the dysfunction severity increases. However, the dispersion of the FSS
      scores indicated a lack of precision in the POPC/PCPC system when compared with
      the more objective and granular FSS. The relationship between the PCPC and the
      FSS-CNS paralleled the relationship between the FSS and POPC/PCPC system.

PMID- 24862464
TI  - Water ice is a soft matrix for the structural characterization of
      glycosaminoglycans by infrared matrix-assisted laser desorption/ionization.
AB  - Glycosaminoglycans (GAGs) are a class of heterogeneous, often highly sulfated
      glycans that form linear chains consisting of up to 100 monosaccharide building
      blocks and more. GAGs are ubiquitous constituents of connective tissue,
      cartilage, and the extracellular matrix, where they have key functions in many
      important biological processes. For their characterization by mass spectrometry
      (MS) and tandem MS, the high molecular weight polymers are usually enzymatically
      digested to oligomers with a low degree of polymerization (dp), typically
      disaccharides. However, owing to their lability elimination of sulfate groups
      upon desorption/ionization is often encountered leading to a loss of information
      on the analyte. Here, we demonstrate that, in particular, water ice constitutes
      an extremely mild matrix for the analysis of highly sulfated GAG disaccharides by
      infrared matrix-assisted laser desorption/ionization (IR-MALDI) mass
      spectrometry. Depending on the degree of sulfation, next to the singly charged
      ionic species doubly- and even triply charged ions are formed. An unambiguous
      assignment of the sulfation sites becomes possible by subjecting sodium adducts
      of the GAGs to low-energy collision-induced dissociation tandem MS. These ionic
      species exhibit a remarkable stability of the sulfate substituents, allowing the
      formation of fragment ions retaining their sulfation that arise from either cross
      ring cleavages or rupture of the glycosidic bonds, thereby allowing an
      unambiguous assignment of the sulfation sites. 

PMID- 24862465
TI  - Role of wetland organic matters as photosensitizer for degradation of
      micropollutants and metabolites.
AB  - Overall photodegradation of pharmaceuticals, personal care products (PPCPs) and
      pharmaceutical metabolites were investigated in order to evaluate their
      photochemical fate in aquatic environments in various natural organic matter
      (NOM) enriched solutions. Tested PPCPs exhibited different rates of loss during
      direct and indirect photolysis. Here, only ultraviolet (UV) light source was used
      for direct photolysis and UV together with (3)DOM(*)for indirect photolysis.
      Diclofenac and sulfamethoxazole were susceptible to photodegradation, whereas
      carbamazepine, caffeine, paraxanthine and tri(2-chloroethyl) phosphate (TCEP)
      showed low levels of photodegradation rate, reflecting their conservative
      photoreactivity. During indirect photodegradation, in contrast to the hydrophilic
      autochthonous NOM, allochthonous NOM with relatively high molecular weight (MW),
      specific ultraviolet absorbance (SUVA) and hydrophobicity (e.g., Suwannee River
      humic acid (SRHA)) revealed to significantly inhibit the photolysis of target
      micropollutants. The presence of Typha wetland NOM enhanced the indirect
      photolysis of well-known conservative micopollutants (carbamazepine and
      paraxanthine). And atenolol, carbamazepine, glimepiride, and N-acetyl
      sulfamethoxazole were found to be sensitive to the triplet excited state of
      dissolved organic matter ((3)DOM(*)) with Typha wetland NOM under deoxygenated
      condition. This suggests that photolysis in constructed wetlands connected to the
      wastewater treatment plant can enhance the degradation of some anthropogenic
      micropollutants by the interaction with (3)DOM(*) in wetlands. 

PMID- 24862466
TI  - A laboratory study of the oxidation of non toxic Cr(III) to toxic Cr(VI) by OH(*)
      free radicals in simulated atmospheric water droplets conditions: potential
      environmental impact.
AB  - In atmospheric waters, oxidation of Cr(III) to Cr(VI) by OH(*) free radicals is a
      major environmental hazard since non-toxic species is transformed into toxic one.
      It is important to obtain some details concerning this oxidation reaction. In
      this study we simulated this oxidation by steady state radiolysis using (60)Co
      radioactive source and pulse radiolysis technique using a 2.5MeV van de Graaff
      electron accelerator and investigated its kinetics in the pH range 1 to 9. Our
      findings showed that the reaction was highly pH dependant with a maximum yield at
      pH 4. The electron transfer proceeds via an inner sphere mechanism with (i)
      formation of the [OH(*)-Cr(III)] adduct with an equilibrium constant of
      2.34*10(4)mol(-1)dm(-3) then (ii) followed by an electron transfer from Cr(III)
      to OH(*) within the adduct with a rate constant of 2.51*10(4)s(-1). The
      implication of this oxidation to atmospheric chromium contamination is discussed.

PMID- 24862467
TI  - Identification of persulfate oxidation products of polycyclic aromatic
      hydrocarbon during remediation of contaminated soil.
AB  - The extent of PAH transformation, the formation and transformation of reaction
      byproducts during persulfate oxidation of polycyclic aromatic hydrocarbons (PAHs)
      in coking plant soil was investigated. Pre-oxidation analyses indicated that
      oxygen-containing PAHs (oxy-PAHs) existed in the soil. Oxy-PAHs including 1H
      phenalen-1-one, 9H-fluoren-9-one, and 1,8-naphthalic anhydride were also produced
      during persulfate oxidation of PAHs. Concentration of 1,8-naphthalic anhydride at
      4h in thermally activated (50 degrees C) persulfate oxidation (TAPO) treatment
      increased 12.7 times relative to the oxidant-free control. Additionally, the oxy
      PAHs originally present and those generated during oxidation can be oxidized by
      unactivated or thermally activated persulfate oxidation. For example, 9H-fluoren
      9-one concentration decreased 99% at 4h in TAPO treatment relative to the
      control. Thermally activated persulfate resulted in greater oxy-PAHs removal than
      unactivated persulfate. Overall, both unactivated and thermally activated
      persulfate oxidation of PAH-contaminated soil reduced PAH mass, and oxidized most
      of the reaction byproducts. Consequently, this treatment process could limit
      environmental risk related to the parent compound and associated reaction
      byproducts. 

PMID- 24862468
TI  - Selective and sensitive detection of aluminium ions in water via fluorescence
      "turn-on" with both solid and water soluble sensory polymer substrates.
AB  - A solid substrate comprised of a cross-linked polymer network is shaped as a film
      with gel-like behaviour and is used to detect aluminium ions in water;
      concurrently, a water soluble sensory polymer synthesised towards the same
      purpose is also discussed. The detection in both systems was achieved via
      fluorescence "turn-on". The limits of detection for Al(III) were 1.6 and 25ppb
      for the former and latter materials, respectively; these levels are significantly
      lower than the EPA recommendations for drinking water. 

PMID- 24862469
TI  - A novel molecularly imprinted material based on magnetic halloysite nanotubes for
      rapid enrichment of 2,4-dichlorophenoxyacetic acid in water.
AB  - A new type of magnetic halloysite nanotubes molecularly imprinted polymer
      (MHNTs@MIP) based on halloysite nanotubes (HNTs) with embedded magnetic
      nanoparticles was introduced in this study. MHNTs@MIP was prepared through
      surface imprinting technology, using 2,4-dichlorophenoxyacetic acid (2,4-D) as a
      template, 4-vinylpyridine as the monomer, divinylbenzene as cross-linking agents,
      and 2,2-azodiisobutyronitrile as initiator. MHNTs@MIP was characterized by
      Fourier Transform Infrared Spectrometer, transmission electron microscopy, X-ray
      diffraction, and vibrating sample magnetometer. MHNTs@MIP exhibited rapid and
      reliable analysis with supermagnetic properties, as well as repeated use and
      template-specific recognition. The adsorption capacity of magnetic halloysite
      nanotubes non-imprinted polymer (MHNTs@NIP) and MHNTs@MIP was 10.3mg/g and
      35.2mg/g, respectively. In the detailed discussion on specific selectivity,
      MHNTs@MIP can be applied as an adsorbent for sample pretreatment extraction and
      obtain high recoveries of about 85-94%. After extraction, high-performance liquid
      chromatography was used to detect 2,4-D residue in water. 

PMID- 24862470
TI  - Inactivation performance and mechanism of Escherichia coli in aqueous system
      exposed to iron oxide loaded graphene nanocomposites.
AB  - The challenge to achieve efficient disinfection and microbial control without
      harmful disinfection byproducts calls for developing new technologies. Magnetic
      graphene oxide (M-GO) with magnetic iron oxide nanoparticles well dispersed on
      graphene oxide (GO) nanosheets exerted excellent antibacterial activity against
      Escherichia coli. The antibacterial performance of M-GO was dependent on the
      concentration and the component mass ratio of M/GO. The synergetic antibacterial
      effect of M-GO was observed with M/GO mass ratio of 9.09. TEM images illustrated
      the interaction between E. coli cells and M-GO nanocomposites. M-GO nanomaterials
      were possible to deposit on or penetrate into cells leading to leakage of
      intercellular contents and loss of cell integrity. The inactivation mechanism of
      E. coli by M-GO was supposed to result from both the membrane stress and
      oxidation stress during the incubation period. M-GO with excellent antibacterial
      efficiency against E. coli and separation-convenient property from water could be
      potent bactericidal nanomaterials for water disinfection. 

PMID- 24862471
TI  - Degradation efficiency and mechanism of azo dye RR2 by a novel ozone aerated
      internal micro-electrolysis filter.
AB  - A newly designed ozone aerated internal micro-electrolysis filter (OIEF) was
      developed to investigate its degradation efficiencies and correlated reaction
      mechanisms of RR2 dye. Complete decolorization and 82% TOC removal efficiency
      were stably achieved in OIEF process. Based on the comprehensive experimental
      results, an empirical equation was proposed to illustrate the effects of initial
      dye concentration and ozone dosage rate on color removal. The results indicated
      that OIEF process could be operated at wide pH range without significant
      treatment efficiencies change, while the optimum pH for RR2 dye degradation was
      9.0. There were 15, 8 and 6 kinds of identified intermediates during ozonation,
      IE and OIEF treatment processes, respectively. Less identified intermediates and
      their lower concentrations in OIEF may attribute to its rather excellent
      mineralization performance. It was found that ozonation, Fe(2+)/Fe(3+) catalyzed
      ozonation, the redox reactions of electro-reduction and electro-oxidation are the
      most important mechanisms in OIEF process. The catalytic effect of Fe(2+)/Fe(3+)
      would induce mutual conversion between dissolved Fe(2+) and Fe(3+), and then
      decrease the dissolution rate of ZVI. The excellent treatment performance proved
      that the OIEF process is one promising technology applied for reactive azo dyes
      and other refractory wastewater treatment. 

PMID- 24862472
TI  - Catalytic wet air oxidation of 2-chlorophenol over sewage sludge-derived carbon
      based catalysts.
AB  - A sewage sludge derived carbon-supported iron oxide catalyst (FeSC) was prepared
      and used in the Catalytic Wet Air Oxidation (CWAO) of 2-chlorophenol (2-CP). The
      catalysts were characterized in terms of elemental composition, surface area,
      pHPZC, XRD and SEM. The performances of the FeSC catalyst in the CWAO of 2-CP was
      assessed in a batch reactor operated at 120 degrees C under 0.9MPa oxygen partial
      pressure. Complete decomposition of 2-CP was achieved within 5h and 90% Total
      Organic Carbon (TOC) was removed after 24h of reaction. Quite a straight
      correlation was observed between the 2-CP conversion, the amount of iron leached
      in solution and the pH of the reaction mixture at a given reaction time,
      indicating a strong predominance of the homogeneous catalysis contribution. The
      iron leaching could be efficiently prevented when the pH of the solution was
      maintained at values higher than 4.5, while the catalytic activity was only
      slightly reduced. Upon four successive batch CWAO experiments, using the same
      FeSC catalyst recovered by filtration after pH adjustment, only a very minor
      catalyst deactivation was observed. Finally, based on all the identified
      intermediates, a simplified reaction pathway was proposed for the CWAO of 2-CP
      over the FeSC catalyst. 

PMID- 24862475
TI  - Nonlinear acoustic properties of ex vivo bovine liver and the effects of
      temperature and denaturation.
AB  - Thermal ablation by high intensity focused ultrasound (HIFU) has a great
      potential for the non-invasive treatment of solid tumours. Due to the high
      pressure amplitudes involved, nonlinear acoustic effects must be understood and
      the relevant medium property is the parameter of nonlinearity B/A. Here, B/A was
      measured in ex vivo bovine liver, over a heating/cooling cycle replicating
      temperatures reached during HIFU ablation, adapting a finite amplitude insertion
      technique, which also allowed for measurement of sound-speed and attenuation. The
      method measures the nonlinear progression of a plane wave through liver and B/A
      was chosen so that numerical simulations matched the measured waveforms. To
      create plane-wave conditions, sinusoidal bursts were transmitted by a 100 mm
      diameter 1.125 MHz unfocused transducer and measured using a 15 mm diameter 2.25
      MHz broadband transducer in the near field. Attenuation and sound-speed were
      calculated using a reflected pulse from the smaller transducer using the larger
      transducer as the reflecting interface. Results showed that attenuation initially
      decreased with heating then increased after denaturation, the sound-speed
      initially increased with temperature and then decreased, and B/A showed an
      increase with temperature but no significant post-heating change. The B/A data
      disagree with other reports that show a significant change and we suggest that
      any nonlinear enhancement in the received ultrasound signal post-treatment is
      likely due to acoustic cavitation rather than changes in tissue nonlinearity. 

PMID- 24862476
TI  - Control of clonorchiasis in Korea: effectiveness of health education for
      community leaders and individuals in an endemic area.
AB  - OBJECTIVES: To develop effective intervention programmes to control Clonorchis
      sinensis infection, three interventions were evaluated in a clonorchiasis-endemic
      area of Korea. METHODS: Four thousand two hundred and sixty-seven voluntary
      participants in Sancheong county were tested at baseline and two follow-up
      surveys after 1 and 3 years. Faecal samples were examined for C. sinensis eggs
      using the Kato-Katz method. Participants were divided into three intervention
      groups by areas and year recruited: national prevention programme only (mass
      health campaign and praziquantel treatment) for Group A; health education for
      community leaders added for Group B; and individual health education added for
      Group C. RESULTS: The prevalence of C. sinensis infection fell substantially in
      all three intervention groups between baseline and 3-year follow-up: from 31.1%
      to 14.9% in Group A, from 29.6% to 6.8% in Group B and from 21.9% to 8.6% in
      Group C. The control effectiveness was highest in Group B with 76.8%. The new
      infection rate was 16.3%, 12.8% and 7.6% in Group A, B and C, respectively. The
      reinfection rate was lower in Group B (3.8%) than Group C (12.2%). CONCLUSIONS:
      To control C. sinensis infection in endemic areas of Korea, health education for
      community leaders or individuals on prevention of C. sinensis infection should be
      added to national control programmes.

PMID- 24862477
TI  - Attachment and eating disorders: a review of current research.
AB  - OBJECTIVE: Attachment insecurity may confer risk for developing an eating
      disorder. We describe domains of attachment functioning that are relevant to
      eating disorders including: affect regulation, interpersonal style, coherence of
      mind, and reflective functioning. Research since 2000 on attachment and eating
      disorders related to these domains is reviewed. METHOD: We searched
      MedLine/Pubmed and PsycINFO from January 2000 to February 2014 and kept articles
      that: were empirical, included adults with a diagnosed eating disorder, and used
      a standard attachment measure. We retained 50 relevant studies. RESULTS: Compared
      to controls, those with eating disorders had higher levels of attachment
      insecurity and disorganized mental states. Lower reflective functioning was
      specifically associated with anorexia nervosa. Attachment anxiety was associated
      with eating disorder symptom severity, and this relationship may be mediated by
      perfectionism and affect regulation strategies. Type of attachment insecurity had
      specific negative impacts on psychotherapy processes and outcomes, such that
      higher attachment avoidance may lead to dropping out and higher attachment
      anxiety may lead to poorer treatment outcomes. DISCUSSION: Research to date
      suggests a possible relationship between attachment insecurity and risk for an
      eating disorder. More research is needed that uses attachment interviews, and
      longitudinal and case control designs. Clinicians can assess attachment
      insecurity to help inform therapeutic stances and interventions.

PMID- 24862478
TI  - Organochlorines in free-range hen and duck eggs from Shanghai: occurrence and
      risk assessment.
AB  - As an important part of the residents' diet in China, the consumption of hen and
      duck eggs has been increasing rapidly in the past decades. Being rich in protein
      and lipid, eggs may be one of the main exposure routes for persistent organic
      pollutants (POPs) to human beings. In this study, four kinds of free-range hen
      and duck eggs were collected from two traditional egg-producing areas in
      Shanghai, namely Dianshan Lake Area and Jinshan Industry Zone. Organochlorine
      pesticides (OCPs, 18 compounds) and polychlorinated biphenyls (PCBs, 14
      compounds) were analyzed with 41 egg samples. Among all OCPs,
      dichlorodiphenyltrichloroethanes (DDTs) were the dominant contaminant, with the
      concentrations ranging from 100 to 730 ng/g, lw. Unlike the 4,4'-DDE as the
      predominant DDTs congener in other three kinds of eggs, the duck eggs from
      Jinshan Industrial Zone had an abnormally high concentration of 2,4'-DDD, which
      may be related to ducks' feedings in the water. The levels of
      hexachlorocyclohexanes (HCHs) and pentachloroanisole (PCA) in eggs from different
      places were similar to each other, while hexchlorobenzene (HCB) for hen eggs from
      Dianshan Lake was much higher than other eggs. According to the results, the DDTs
      residues detected in this study were mainly due to the historical usage, whereas
      the high ratio of gamma-HCH/alpha-HCH suggested that there might be some recent
      input of lindane in these two areas. For PCBs, the congener profiles varied among
      species. Low molecular PCBs (Tri-PCBs and Tetra-PCBs) were main congeners for
      duck eggs from Dianshan Lake and all hen eggs, while high molecular PCBs
      accounted for more than 50 % for duck eggs from Jinshan Industrial Zone, which
      was consistent with the water analysis results of the synchronous study from our
      group. This study suggests that Dianshan Lake Area may not be a good reference
      area for POPs monitoring in Shanghai. The estimated daily intakes of DDTs, HCHs,
      HCBs, and PCBs were far below the reference limits, showing no significant health
      risk for human consumption by eating eggs collected in this study.

PMID- 24862479
TI  - Changes of turbidity during the phenol oxidation by photo-Fenton treatment.
AB  - Turbidity presented by phenol solutions oxidized with Fenton reagent shows the
      tendency of a first order intermediate kinetics. Thus, turbidity can be
      considered a representative parameter of the presence of intermediate oxidation
      species, which are generated along the decomposition of toxic and reluctant
      contaminants, such as phenol. Moreover, that parameter presents a linear
      dependence with the catalyst dosage, but is also determined by the initial
      contaminant load. When analyzing the oxidation mechanism of phenol, it is found
      that the maximum turbidity occurs when the treatment is carried out at oxidant to
      phenol molar ratios R = 4.0. These oxidation conditions correspond to the
      presence of a reaction mixture mainly composed of dihydroxylated rings,
      precursors of the muconic acid formation. The oxidation via "para" comprises the
      formation reactions of charge transfer complexes (quinhydrone), between the para
      dihydroxylated intermediates (hydroquinone) and the para-substituted quinones (p
      benzoquinone), which are quite unstable and reactive species, quickly decomposed
      into hydroxyhydroquinones. Working with oxidant ratios up to R = 6.0, the maximum
      observed value of turbidity in the oxidized solutions is kept almost constant. It
      is found that, in these conditions, the pyrogallol formation is maximal, what is
      generated through the degradation of ortho-species (catechol and ortho
      benzoquinone) and meta-substituted (resorcinol). Operating with ratios over R =
      6.0, these intermediates are decomposed into biodegradable acids, generating
      lower turbidity in the solution. Then, the residual turbidity is a function of
      the molar ratio of the ferrous ions vs. moles of oxidant utilized in the essays,
      that lets to estimate the stoichiometric dosage of catalyst as 20 mg/L at pH =
      3.0, whereas operating in stoichiometric conditions, R = 14.0, the residual
      turbidity of water results almost null.

PMID- 24862480
TI  - Effect of industrial waste products on phosphorus mobilisation and biomass
      production in abattoir wastewater irrigated soil.
AB  - This study evaluated the effect of alkaline industrial by-products such as flyash
      (FA) and redmud (RM) on phosphorus (P) mobilisation in abattoir wastewater
      irrigated soils, using incubation, leaching and plant growth (Napier grass
      [Pennisetum purpureum]) experiments. The soil outside the wastewater irrigated
      area was also collected and treated with inorganic (KH2PO4 [PP]) and organic
      (poultry manure [PM]) P treatments, to study the effect of FA and RM on P
      mobilisation using plant growth experiment. Among the amendments, FA showed the
      highest increase in Olsen P, oxalic acid content and phosphatase activity. The
      highest increase in Olsen P for PM treated non-irrigated soils showed the ability
      of FA and RM in mobilising organic P better than inorganic P (PP). There was over
      85 % increase in oxalic acid content in the plant growth soils compared to the
      incubated soil, showing the effect of Napier grass in the exudation of oxalic
      acid. Both amendments (FA and RM) showed an increase in phosphatase activity at
      over 90 % at the end of the 5-week incubation period. The leaching experiment
      indicated a decrease in water soluble P thereby ensuring the role of FA and RM in
      minimising P loss to water bodies. FA and RM showed an increase in plant biomass
      for all treatments, where FA amended soil showed the highest increase as evident
      from FA's effect on Olsen P. Therefore, the use of FA and RM mobilised P in
      abattoir wastewater irrigated soils and increased biomass production of Napier
      grass plants through root exudation of oxalic acid.

PMID- 24862481
TI  - Distribution, possible sources, and health risk assessment of SVOC pollution in
      small streams in Pearl River Delta, China.
AB  - The pollution levels of typical semivolatile organic compounds (SVOCs) consisting
      of 15 polycyclic aromatic hydrocarbons (PAHs), 20 organic chlorinated pesticides
      (OCPs), and 15 phthalate esters (PAEs) were investigated in small rivers running
      through the flourishing cities in Pearl River Delta region, China. The
      concentrations of ?15PAHs were 2.0-48 ng/L and 29-1.2 * 10(3) ng/g in the water
      and sediment samples, respectively. The ?20OCPs were 6.6-57 ng/L and 9.3-6.0 *
      10(2) ng/g in the water and sediment samples, respectively. The concentrations of
      ?15PAEs were much higher both in the water and sediments. The partition process
      of the detected SVOCs between the water and sediment did not reach the
      equilibrium state at most of the sites when sampling. The combustion of petroleum
      products and coal was the major source of the detected PAHs. The OCPs were mainly
      historical residue, whereas the new inputs of dichlorodiphenyltrichloroethane
      (DDT), chlordane, and endosulfan were possible at several sites. The industrial
      and domestic sewage were the major source for the PAEs; storm water runoff
      accelerated the input of PAEs. No chronic risk of the SVOCs was identified by a
      health risk assessment through daily water consumption, except for the ?20OCPs
      that might cause cancer at several sites. Nevertheless, the integrated health
      risk of the SVOCs should not be neglected and need intensive investigations.

PMID- 24862483
TI  - Pathways of reductive degradation of crystal violet in wastewater using free
      strain Burkholderia vietnamiensis C09V.
AB  - A new strain isolated from activated sludge and identified as Burkholderia
      vietnamiensis C09V was used to biodegrade crystal violet (CV) from aqueous
      solution. To understand the degradation pathways of CV, batch experiments showed
      that the degradation using B. vietnamiensis C09V significantly depended on
      conditions such as pH, initial dye concentration and media components, carbon and
      nitrogen sources. Acceleration in the biodegradation of CV was observed in
      presence of metal ions such as Cd and Mn. More than 98.86C of CV (30 mg l(-1))
      was degraded within 42 h at pH 5 and 30  degrees C. The biodegradation kinetics
      of CV corresponded to the pseudo first-order rate model with a rate constant of
      0.046 h(-1). UV-visible and Fourier transform infrared spectroscopy (FTIR) were
      used to identify degradation metabolites. Which further confirmed by LC-MS
      analysis, indicating that CV was biodegraded to N,N-dimethylaminophenol and
      Michler's ketone prior to these intermediates being further degraded. Finally,
      the ability of B. vietnamiensis C09V to remove CV in wastewater was demonstrated.

PMID- 24862482
TI  - Degradation of polycyclic aromatic hydrocarbons in a coking wastewater treatment
      plant residual by an O3/ultraviolet fluidized bed reactor.
AB  - Coking wastewater treatment plant (CWWTP) represents a typical point source of
      polycyclic aromatic hydrocarbons (PAHs) to the water environment and threatens
      the safety of drinking water in downstream regions. To enhance the removal of
      residual PAHs from bio-treated coking wastewater, a pilot-scale O3/ultraviolet
      (UV) fluidized bed reactor (O3/UV FBR) was designed and different operating
      factors including UV irradiation intensity, pH, initial concentration, contact
      time, and hydraulic retention time (HRT) were investigated at an ozone level of
      240 g h(-1) and 25 +/- 3  degrees C. A health risk evaluation and cost analysis
      were also carried out under the continuous-flow mode. As far as we know, this is
      the first time an O3/UV FBR has been explored for PAHs treatment. The results
      indicated that between 41 and 75 % of 18 target PAHs were removed in O3/UV FBR
      due to synergistic effects of UV irradiation. Both increased reaction time and
      increased pH were beneficial for the removal of PAHs. The degradation of the
      target PAHs within 8 h can be well fitted by the pseudo-first-order kinetics (R
      (2) > 0.920). The reaction rate was also positively correlated with the initial
      concentrations of PAHs. The health risk assessment showed that the total amount
      of carcinogenic substance exposure to surface water was reduced by 0.432 g day(
      1). The economic analysis showed that the O3/UV FBR was able to remove 18 target
      PAHs at a cost of US$0.34 m(-3). These results suggest that O3/UV FBR is
      efficient in removing residuals from CWWTP, thus reducing the accumulation of
      persistent pollutant released to surface water.

PMID- 24862484
TI  - Fate of pharmaceutical compounds and steroid hormones in soil: study of transfer
      and degradation in soil columns.
AB  - Numerous chemical products are dispersed into the environment, and the
      consequences can be sometimes harmful to humans and ecosystems. Pharmaceutical
      compounds and hormone steroids are among these substances that concern the
      scientific community. Currently, little data are available on the presence and
      fate of these compounds in the environment and, in particular, for solid
      matrices. Therefore, the aim of this work was to perform soil column experiments
      to evaluate the accumulation, transfer and degradation of these substances in
      soil. The analyses were based on efficient sample preparation followed by
      sensitive and selective liquid chromatography coupled to tandem mass spectrometry
      (LC-MS/MS). For this purpose, 23 compounds were chosen including both
      pharmaceutical compounds as well as steroid hormones. In addition, this
      experiment was performed on two soils with different properties (% clay, pH,
      etc.). To the best of our knowledge, no soil column experiments have been
      performed previously on a large number of pharmaceutical compounds and steroid
      hormones. Significant transfer was observed only for sulphonamides that can be
      justified by their polarity (log K ow < 3). Furthermore, some compounds have a
      cationic characteristic and are likely to be not much mobiles in soil due to
      cation exchange process. However, it was observed that the migration of the
      substances depends on the soil characteristics, such as the amount of clay and
      the pH values. Regarding the degradation, it was noticed that substances degraded
      rapidly in the two soils. Indeed, for most substances, their half-lives were
      lower than 20 days. Furthermore, it was observed that the degradation rate
      depended on the soil.

PMID- 24862485
TI  - Catalytic wet air oxidation of bisphenol A solution in a batch-recycle trickle
      bed reactor over titanate nanotube-based catalysts.
AB  - Catalytic wet air oxidation (CWAO) is classified as an advanced oxidation
      process, which proved to be highly efficient for the removal of emerging organic
      pollutant bisphenol A (BPA) from water. In this study, BPA was successfully
      removed in a batch-recycle trickle-bed reactor over bare titanate nanotube-based
      catalysts at very short space time of 0.6 min gCAT g(-1). The as-prepared
      titanate nanotubes, which underwent heat treatment at 600  degrees C, showed high
      activity for the removal of aqueous BPA. Liquid-phase recycling (5- or 10-fold
      recycle) enabled complete BPA conversion already at 200  degrees C, together with
      high conversion of total organic carbon (TOC), i.e., 73 and 98 %, respectively.
      The catalyst was chemically stable in the given range of operating conditions for
      189 h on stream.

PMID- 24862487
TI  - Long-term efficacy of polydimethylsiloxane (Macroplastique) injection for
      Mitrofanoff leakage after continent urinary diversion surgery.
AB  - OBJECTIVE: To assess the long-term efficacy of polydimethylsiloxane
      (Macroplastique) injection (MPI) in the treatment of Mitrofanoff leakage
      secondary to valve incompetence. PATIENTS AND METHODS: Between 1995 and 2012, the
      records of 24 consecutive patients who underwent MPI for Mitrofanoff urinary
      leakage after continent cutaneous urinary diversion (CCUD) surgery were examined.
      All patients had a valve deemed of sufficient length (>2 cm) to attempt
      Macroplastique coaptation. Treatment outcomes were divided into three categories
      based on physician assessment: success (dry), partial success (>50% reduction in
      incontinence pads) and failure. Success rates were assessed according to the type
      of reservoir and conduit channel. RESULTS: The mean (range) follow-up was 30 (6
      96) months. One patient had initial difficulty catheterising, and subsequently
      required major revision surgery. In all, 12 patients (50%) failed the treatment
      and subsequently underwent operative revision to the channel. Three patients
      (12.5%) achieved complete success; one patient had an appendix channel through
      native bladder and the remaining two had Monti channels through colon. Nine
      patients (37.5%) had partial success; success rates were higher with appendix
      channels (four of six) and colonic reservoirs (six of seven) when compared with
      Monti channels (eight of 18, 44%) and ileal reservoirs (zero of two). Five of the
      nine patients with partial success eventually required further surgical revision
      for deteriorating continence at a mean (range) of 41 (14-96) months, whilst the
      other four have maintained sufficient continence with MPI alone. CONCLUSION:
      Macroplastique bulking cured only 12.5% patients, but leakage was substantially
      improved in a further 37.5% allowing major surgery to be avoided or postponed in
      one half of the cohort. Appendix Mitrofanoffs do better than the Monti
      Mitrofanoff, with channels through colonic segments generally doing better than
      those through ileal bladders. MPI should be considered as a less invasive
      alternative to avoid or delay major reconstructive surgery.

PMID- 24862486
TI  - Impact of raw pig slurry and pig farming practices on physicochemical parameters
      and on atmospheric N2O and CH 4 emissions of tropical soils, Uvea Island (South
      Pacific).
AB  - Emissions of CH4 and N2O related to private pig farming under a tropical climate
      in Uvea Island were studied in this paper. Physicochemical soil parameters such
      as nitrate, nitrite, ammonium, Kjeldahl nitrogen, total organic carbon, pH and
      moisture were measured. Gaseous soil emissions as well as physicochemical
      parameters were compared in two private pig farming strategies encountered on
      this island on two different soils (calcareous and ferralitic) in order to
      determine the best pig farming management: in small concrete pens or in large
      land pens. Ammonium levels were higher in control areas while nitrate and nitrite
      levels were higher in soils with pig slurry inputs, indicating that nitrification
      was the predominant process related to N2O emissions. Nitrate contents in soils
      near concrete pens were important (>= 55 MUg N/g) and can thus be a threat for
      the groundwater. For both pig farming strategies, N2O and CH4 fluxes can reach
      high levels up to 1 mg N/m(2)/h and 1 mg C/m(2)/h, respectively. CH4 emissions
      near concrete pens were very high (>= 10.4 mg C/m(2)/h). Former land pens
      converted into agricultural land recover low N2O emission rates (<= 0.03 mg
      N/m(2)/h), and methane uptake dominates. N2O emissions were related to nitrate
      content whereas CH4 emissions were found to be moisture dependent. As a result
      relating to the physicochemical parameters as well as to the gaseous emissions,
      we demonstrate that pig farming in large land pens is the best strategy for
      sustainable family pig breeding in Uvea Islands and therefore in similar small
      tropical islands.

PMID- 24862488
TI  - Application of proteomics to determine the mechanism of action of traditional
      Chinese medicine remedies.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The rationale for using traditional Chinese
      medicine (TCM) is based on the experience that has been gained from its wide use
      over thousands of years. However, the mechanisms of action of many TCM are still
      unclear. Proteomics, which mainly characterizes protein functions, protein
      protein interactions, and protein modification in tissues or animals, can be used
      to investigate signaling pathway perturbations in cells or the whole body.
      Proteomics has improved the discovery process of effective TCM compounds, and has
      helped to elucidate their possible mechanisms of action. Therefore, a systematic
      review of the application of proteomics on TCM research is of great importance
      and necessity. This review strives to describe the literature on the application
      of proteomics to elucidate the mechanism of action of TCM on various diseases,
      and provide the essential discussion on the further utilization of proteomics
      data to accelerate TCM research. MATERIALS AND METHODS: Literature survey was
      performed via electronic search on Pubmed with keywords 'Proteomics' and
      'Traditional Chinese Medicine'. The papers written in English were acquired and
      analyzed in this review. RESULTS: This review mainly summarizes the application
      of proteomics to investigate TCM remedies for neuronal disease, cancer,
      cardiovascular disease, diabetes, and immunology-related disease. CONCLUSIONS:
      Researchers have applied proteomics to study the mechanism of action of TCM and
      made substantial progresses. Further studies are required to determine the
      protein targets of the active compounds, analyze the mechanism of actions in
      patients, compare the clinical effects with western medicine.

PMID- 24862489
TI  - Concentrated green tea extract induces severe acute hepatitis in a 63-year-old
      woman--a case report with pharmaceutical analysis.
AB  - ETNOPHARMACOLOGICAL RELEVANCE: The popularity of concentrated green tea extracts
      as dietary supplements for a wide range of applications is increasing due to
      their health-promoting effects attributed to the high amounts of catechins they
      contain. The most important of the green tea catechins is (-)-epigallocatechin-3
      O-gallate (EGCG). While their beneficiary effects have been studied extensively,
      a small number of adverse events have been reported in the medical literature.
      Here we present a typical reversible course of severe hepatitis after green tea
      consumption. MATERIALS AND METHODS: The case study describes in a 63-year old
      woman during treatment with green tea-capsules upon recommendation of a cancer
      support group. RESULTS: The histological finding was consistent with drug induced
      hepatitis, and other possible causes of hepatitis were excluded. According to the
      CIOMS/RUCAM score the causality was assessed as "probable". After discontinuation
      of medication, followed by extracorporal albumin dialysis, rapid and sustained
      recovery occurred. Pharmaceutically analysis (HPLC) of the green tea capsules did
      not give evidence for contaminants but revealed the two typical compounds of
      green tea, namely (-)-epigallocatechin-3-O-gallate (EGCG, 93.2%) and epicatechin
      (EC, 6.8%) at a very high dose level. CONCLUSION: The present case highlights the
      fact that such concentrated herbal extracts from green tea may not be free of
      adverse effects under certain circumstances. There is still a lack of a uniform
      European Union-wide surveillance system for adverse drug reactions of herbal
      products. Therefore this case underlines the importance of public awareness in
      the potential risks in use of herbal products.

PMID- 24862490
TI  - Ethnobotanical study of indigenous knowledge on medicinal and nutritious plants
      used to manage opportunistic infections associated with HIV/AIDS in western
      Uganda.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Traditional medicine plays an important role in
      the daily lives of the people of Uganda to treat a wide range of health problems.
      Our study presents results of an ethnobotanical inventory conducted to identify
      and document medicinal and nutritional plants used in the management of
      opportunistic infections associated with human immunodeficiency virus / acquired
      immunodeficiency syndrome (HIV/AIDS), the plant parts used, preparation and
      administration methods of herbal remedies. MATERIALS AND METHODS: We performed
      semi-structured interviews with 79 respondents (women 78%, men 22%), who included
      specialists in medicinal plants (such as traditional birth attendants and
      herbalists) and non specialists with general knowledge of plant use. Respondents
      answered a semi-structured questionnaire regarding their knowledge of plants and
      general treatment practices including management of HIV/AIDS opportunistic
      infections. The reported plants were collected and identified. Data were analyzed
      using factor informant consensus and fidelity level to determine homogeneity of
      informants' knowledge on medicinal and nutritional plants suitable for different
      ailment categories and the most preferred plant species used to treat each
      ailment category in the study areas. RESULTS: The study revealed 148 plant
      species belonging to 54 families, most of which were herbs (50.7%). Leaves
      (61.6%) were the most frequently used parts in remedy preparations which were
      mainly administered orally (72%). The majority of plants (62%) were harvested
      from wild habitats. The most important species according to fidelity values are
      Hibiscus sabdariffa L. for anaemia, Mangifera indica L. for cough, Zehneria
      scabra (L. F.) Sond. for skin infections, Rhus natalensis Bernh.ex.Krauss for
      diarrhoea and Tarenna pavettoides (Harv.) Sim for appetite boosting. The factor
      informant consensus highlighted the agreement in the use of plants and showed
      that the respiratory infections category had the greatest agreement (0.60).
      Family Asteraceae accounted for 15% of the total species recorded. Sixty plant
      species (40%) of the plants provide nutritional support. CONCLUSION: The study
      revealed that folk medicine is still widely practised. Fidelity level values
      indicate that these plants are the most preferred species for particular
      ailments. The high consensus value (0.6) indicated that there was high agreement
      in the use of plants for respiratory ailments among others. These preferred plant
      species could be prioritized for conservation and subjected to chemical screening
      to ascertain their pharmacological activities.

PMID- 24862491
TI  - Involvement of NFkappaB in the antirheumatic potential of Chenopodium album L.,
      aerial parts extracts.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Chenopodium album L. (C. album) is commonly known
      as Bathua in Hindi (Family: Chenopodiaceae). Traditionally, the plant is used as
      a laxative, diuretic, sedative and the infusion of the plant is used for the
      treatment of rheumatism. However, no scientific validation is available on the
      antirheumatic potential of the plant. In the present investigation, role of NF
      kappa B (NFkappaB) in the antiarthritic potential of extracts of aerial parts of
      Chenopodium album was explored and evaluated. METHODS: The defatted aerial parts
      of Chenopodium album were successively extracted with ethylacetate, acetone,
      methanol and 50% methanol to study their antioxidant capacity followed by
      antiarthritic potential using Complete Freund's adjuvant (CFA) induced arthritis
      model in rats. The polyphenol, flavonoid and flavanone contents of different
      extracts were quantified and correlated with their antioxidant capacity,
      antiarthritic activity and NFkappaB inhibition potential. RESULTS: The
      experimental data indicated that the acetone extract of Chenopodium album (ACCA)
      has shown significant reduction in rat paw edema (80.13%) at dose level of 200
      mg/kg per oral in 21 days of this study. On 22nd day, hematological and
      biochemical parameters were estimated and it was observed that the altered
      hematological parameters (Hb, RBC, WBC and ESR), biochemical parameters (Serum
      creatinine, total proteins and acute phase proteins) and loss in body weight in
      the arthritic rats were significantly brought back to near normal level by the
      ACCA extract. ACCA extract significantly decreased the NFkappaB expression in
      paraventricular nucleus of hypothalamus and this effect is comparable with
      standard indomethacine in CFA treated rats. The polyphenolic and flavonoid
      content of different extracts were in the range of 14.56+/-0.21-42.00+/-0.2 mg
      (gallic acid equivalent/g extract) and 2.20+/-0.003-7.33+/-0.5 mg (rutin
      equivalent/g extract) respectively. CONCLUSION: The antiarthritic activity
      possessed by ACCA extract can be correlated directly to its antioxidant
      potential, high flavonoidal content achieved by successive extraction and its
      capacity to inhibit the NFkappaB protein, as proven by immunohistochemistry
      study.

PMID- 24862492
TI  - HS-23, Lonicera japonica extract, attenuates septic injury by suppressing toll
      like receptor 4 signaling.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Lonicera japonica Thunberg is a traditional
      herbal medicine widely used in East Asia as an anti-bacterial, anti-inflammatory,
      and antiviral agent. This study was designed to investigate the effects of HS-23,
      ethanol extract of the dried flower buds of Lonicera japonica, in experimental
      models of sepsis and elucidate the mechanisms of action of HS-23. MATERIALS AND
      METHODS: Male ICR mice were intravenously administered HS-23 (20 and 40 mg/kg)
      for 0 (immediately) and 24 h after cecal ligation and puncture (CLP) for survival
      tests, and HS-23 (40 mg/kg) immediately after CLP for biochemical assays.
      RESULTS: HS-23 improved sepsis-induced mortality, enhanced bacterial clearance,
      and attenuated multiple organ failure. The mechanisms of action of HS-23 included
      attenuation of increased toll-like receptor (TLR)4 protein and mRNA expression.
      HS-23 suppressed sepsis-induced increases in protein expression of myeloid
      differentiation primary response protein 88, p38 and c-Jun N-terminal kinase in
      both liver and lung, as well as TIR-domain-containing adapter-inducing interferon
      beta and interferon regulatory transcription factor 3 protein expression in
      liver. CONCLUSION: The results of this study revealed that HS-23 attenuated
      sepsis through suppression of TLR signaling pathways. Therefore, our findings
      suggest that HS-23 might be useful as a potential therapeutic agent for treatment
      of sepsis.

PMID- 24862493
TI  - Anti-arthritic activity of Xanthium strumarium L. extract on complete Freund's
      adjuvant induced arthritis in rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Xanthium strumarium L. fruit (Xanthiu fruit) has
      been traditionally used as a medicinal herb in China for the treatment of many
      ailments including rheumatoid arthritis. However, the anti-arthritic activity of
      Xanthium strumarium fruit has still not been demonstrated. In the present study,
      we confirmed that the extract of Xanthium strumarium (EXS) prevents rheumatoid
      arthritis induced by Complete Freund's Adjuvant (CFA) in rats. MATERIALS AND
      METHODS: Male Wistar rats (160+/-10 g) were immunized by intradermal injection of
      0.1 mL of CFA into the left hind metatarsal footpad. EXS was administered orally
      at a dose of 300 and 75 mg/kg once a day after the induction of adjuvant
      arthritis. Methotrexate (3 mg/kg, twice a week) was used as a positive control.
      Paw swelling, arthritic score, body weight loss, spleen index, thymus index,
      serum cytokines, inflammatory mediators and histological change were measured.
      The chemical profile of EXS was analyzed by HPLC-DAD. RESULTS: We found that the
      EXS significantly suppressed paw swelling and arthritic score, increased body
      weight loss and decreased the thymus index. The overproduction of TNF-alpha and
      IL-1beta were remarkably suppressed in the serum of all EXS-treated rats, and in
      contrast IL-10 was markedly increased. The level of COX-2 and 5-LOX was also
      decreased with EXS treatment. Ten phenolic acid derivatives were identified from
      14 detected peaks by HPLC-DAD with the reference substances and verified by LC
      MS. CONCLUSIONS: These results suggest the potential effect of EXS as an anti
      arthritis agent towards CFA-induced arthritis in rats. Xanthium strumarium has
      the potential to be regarded as a candidate for use in general therapeutics and
      as an immune-modulatory medicine in rheumatoid arthritis.

PMID- 24862494
TI  - Predictive value of gelsolin for the outcomes of preterm neonates: a pilot study.
AB  - BACKGROUND: Plasma gelsolin is a circulating actin-binding protein that has a
      protective role against tissue injuries. Our aim was to compare the baseline
      levels of gelsolin in premature infants with neonatal outcomes. METHODS: A total
      of 32 preterm neonates born at 23-32 weeks of gestation were enrolled in the
      study. RESULTS: Plasma gelsolin levels at 72 h were significantly lower in
      patients with respiratory distress syndrome, in patients who were administered
      surfactant therapy and in patients who developed sepsis (P < 0.05). Plasma
      gelsolin levels at 28 days were significantly lower in patients who developed
      bronchopulmonary dysplasia and retinopathy of prematurity (P < 0.05).
      CONCLUSIONS: Low plasma gelsolin levels in the first postnatal month may be
      associated with poor outcomes in premature infants.

PMID- 24862495
TI  - The influence of oral Veillonella species on biofilms formed by Streptococcus
      species.
AB  - Oral Veillonella, Veillonella atypica, Veillonella denticariosi, Veillonella
      dispar, Veillonella parvula, Veillonella rogosae, and Veillonella tobetsuensis
      are known as early colonizers in oral biofilm formation. To investigate the role
      of oral Veillonella, biofilms formed by the co-culture of Streptococcus gordonii,
      Streptococcus mutans, Streptococcus salivarius, or Streptococcus sanguinis, with
      oral Veillonella were examined at the species level. The amount of biofilm formed
      by S. mutans, S. gordonii, and S. salivarius in the presence of the six
      Veillonella species was greater than that formed in the control experiments, with
      the exception of S. mutans with V. dispar. In contrast, in the case of biofilm
      formation by S. sanguinis, the presence of Veillonella species reduced the amount
      of the biofilm, with the exception of V. parvula and V. dispar. The time
      dependent changes in the amount of biofilm and the number of planktonic cells
      were grouped into four patterns over the 24 combinations. Only that of S.
      gordonii with V. tobetsuensis showed a unique pattern. These results indicate
      that the mode of action of this combination differed from that of the other
      combinations with respect to biofilm formation. It is possible that there may be
      several factors involved in the interaction between Streptococcus and Veillonella
      species. 

PMID- 24862497
TI  - Three new cyclopentenone derivatives from Actinoalloteichus nanshanensis NEAU
      119.
AB  - Three new cyclopentenone derivatives (1-3) were isolated from the rare
      actinomycete Actinoalloteichus nanshanensis NEAU 119. Their structures were
      elucidated by extensive spectroscopic analysis. Compound 1 showed moderate
      cytotoxic activity against human lung adenocarcinoma cell line A549, human
      leukemia cell line K562, and human renal carcinoma cell line ACHN with an IC50 of
      14.67, 11.87, and 23.36 MUg ml(-1), respectively.

PMID- 24862496
TI  - Brief report: cognitive flexibility in autism spectrum disorders: a quantitative
      review.
AB  - Impairments in cognitive flexibility have been used to characterize the
      neuropsychological presentation of persons with autism spectrum disorders (ASDs).
      Previous studies have yielded mixed results. Our objective was to systematically
      review the sensitivity of cognitive flexibility measures in ASD using
      quantitative methods employed by meta-analytic statistical techniques. Seventy
      two studies met inclusion criteria for analysis and included a total of 2,137
      individuals with ASD and 2,185 healthy controls. Our findings demonstrate that
      while the shift sub-scale of the self-report version of the Behavioral Rating
      Inventory of Executive Function (BRIEF) showed approximate absolute
      discriminability, of all the performance measures that were systematically
      reviewed and evaluated, none could reliably differentiate between individuals
      with ASD and controls; this is not surprising given that cognitive flexibility is
      not a core deficit of ASD. Our findings suggest that while the shift sub-scale of
      the self-report version of the BRIEF is a promising clinical marker, clinical
      performance measures of cognitive flexibility may lack ecological validity and
      lastly, reinforces that impairments in cognitive flexibility do not uniformly
      characterize all persons with ASD. 

PMID- 24862498
TI  - Cardiovascular Z-scores in fetuses with tetralogy of Fallot.
AB  - OBJECTIVE: To establish formulae for the calculation of fetal cardiovascular Z
      scores based on femur length (FL), and to compare cardiovascular parameters
      between fetuses with tetralogy of Fallot (TOF) and normal fetuses in order to
      assess their value for the prenatal diagnosis of TOF. METHODS: A total of 329
      normal fetuses and 43 fetuses with TOF were included in this study. Eleven
      cardiovascular dimensions were measured offline after cardiac spatiotemporal
      image correlation volume acquisition. Normal cardiovascular Z-score formulae were
      constructed for these measurements based on FL by performing a standard
      regression analysis followed by weighted regression of absolute residual values.
      The following ratios were calculated: right ventricular internal diameter (RVID)
      to left ventricular internal diameter (LVID) and pulmonary artery diameter (PA)
      to aorta diameter (Ao). Subsequently, all parameters were compared between the
      normal and TOF groups. RESULTS: Formulae for calculating Z-scores for the 11
      cardiovascular dimensions were constructed. FL was significantly correlated with
      all cardiovascular dimensions assessed (r = 0.816-0.944, P < 0.001 for all).
      RVID, Ao, PA, aortic arch isthmus, and ductus arteriosus mean Z-scores and PA/Ao
      ratio were statistically significantly different between normal fetuses and those
      with TOF. In the TOF group, all Ao Z-scores (43/43) were > + 2 and all PA/Ao
      ratios (43/43) were below the normal 95% range. However, only 48.8% (21/43) of
      the PA Z-scores were < -2. CONCLUSIONS: The cardiovascular Z-score formulae
      developed can provide a quantitative basis for the prenatal diagnosis of TOF.
      Aortic dilatation and abnormal PA/Ao ratio may be markers for the antenatal
      diagnosis of TOF.

PMID- 24862499
TI  - Oncoplastic breast surgery with oxidized regenerated cellulose: appraisals based
      on five-year experience.

PMID- 24862500
TI  - Evaluation and management of hyponatraemia in children.
AB  - AIM: Paediatric hyponatraemia is usually caused by an excess of antidiuretic
      hormone and may lead to serious neurological complications. It is challenging for
      clinicians to differentiate between conditions causing excess water and salt
      loss. This review analyses individual causes of hyponatraemia and focuses on
      optimal diagnostic algorithms and treatment strategies. CONCLUSION: Correct
      evaluation of hyponatraemia requires proper understanding of the aetiology and
      appropriate management calls for a detailed history, physical examination and
      specific laboratory investigations.

PMID- 24862501
TI  - High-throughput rare cell separation from blood samples using steric hindrance
      and inertial microfluidics.
AB  - The presence and quantity of rare cells in the bloodstream of cancer patients
      provide a potentially accessible source for the early detection of invasive
      cancer and for monitoring the treatment of advanced diseases. The separation of
      rare cells from peripheral blood, as a "virtual and real-time liquid biopsy", is
      expected to replace conventional tissue biopsies of metastatic tumors for therapy
      guidance. However, technical obstacles, similar to looking for a needle in a
      haystack, have hindered the broad clinical utility of this method. In this study,
      we developed a multistage microfluidic device for continuous label-free
      separation and enrichment of rare cells from blood samples based on cell size and
      deformability. We successfully separated tumor cells (MCF-7 and HeLa cells) and
      leukemic (K562) cells spiked in diluted whole blood using a unique complementary
      combination of inertial microfluidics and steric hindrance in a microfluidic
      system. The processing parameters of the inertial focusing and steric hindrance
      regions were optimized to achieve high-throughput and high-efficiency separation,
      significant advantages compared with existing rare cell isolation technologies.
      The results from experiments with rare cells spiked in 1% hematocrit blood
      indicated >90% cell recovery at a throughput of 2.24 * 10(7) cells min(-1). The
      enrichment of rare cells was >2.02 * 10(5)-fold. Thus, this microfluidic system
      driven by purely hydrodynamic forces has practical potential to be applied either
      alone or as a sample preparation platform for fundamental studies and clinical
      applications. 

PMID- 24862502
TI  - Tackling the "quality of life" conundrum.

PMID- 24862505
TI  - Two-step synthesis of multi-substituted amines by using an N-methoxy group as a
      reactivity control element.
AB  - The development of a two-step synthesis of multi-substituted N-methoxyamines from
      N-methoxyamides is reported. Utilization of the N-methoxy group as a reactivity
      control element was the key to success in this two-step synthesis. The first
      reaction involves a N-methoxyamide/aldehyde coupling reaction. Whereas ordinary
      amides cannot condense with aldehydes intermolecularly due to the poor
      nucleophilicity of the amide nitrogen, the N-methoxy group enhances the
      nucleophilicity of the nitrogen, enabling the direct coupling reaction. The
      second reaction in the two-step process was nucleophilic addition to the N
      methoxyamides. Incorporation of the N-methoxy group into the amides increased the
      electrophilicity of the amide carbonyls and promoted the chelation effect. This
      nucleophilic addition enabled quick diversification of the products derived from
      the first step. The developed strategy was applicable to a variety of substrates,
      resulting in the elaboration of multi-substituted piperidines and acyclic amines,
      as well as a substructure of a complex natural alkaloid. 

PMID- 24862506
TI  - Fine needle aspiration cytology of nodular fasciitis of the breast.
AB  - We report a case of nodular fasciitis (NF) of the breast, which was cytologically
      diagnosed as a spindle cell proliferation with undetermined malignant potential.
      Owing to small size of the lesion (5.9 * 3.7 * 4.1 mm), only fine needle
      aspiration (FNA) cytology was performed under ultrasound guidance. The FNA smears
      were cellular, rich in single/clustered spindle cells but mammary ductal
      epithelial/myoepithelial cells were absent. These cytologic findings suggested
      spindle cell growth of mesenchymal origin. Pattern-less arrangement of spindle
      cells, heterogeneous composition of the stromal matrix, lack of nuclear/cellular
      atypia, occasional mitosis but no aberrant mitotic figures, and lymphocyte
      infiltration indicated reactive rather than neoplastic nature of the lesion.
      Nonetheless, lumpectomy was conducted because the possibility of neoplasm was not
      completely ruled out. The histologic diagnosis of the resected nodule was NF. FNA
      specimens were reviewed thoroughly in an attempt to define the key
      cytomorphologic features of NF that are important for the correct diagnosis.
      Differential diagnoses from the lesions that show similar cytologic pictures are
      discussed in detail. Although NF arising from the breast is rare,
      cytopathologists should be aware of its clinical and cytopathologic
      characteristics. Knowledge of the possibility of NF in the breast and its
      cytologic findings may help cytopathologists to discern its reactive, not
      neoplastic, characteristics of the lesion. If the referring surgeon is alerted NF
      as a possibility along with other differential diagnoses, close observation would
      become a management option. In-depth discussion of cytologic features and a
      review of the pertinent literature are also included.

PMID- 24862508
TI  - Velocity-selective adaptation of the horizontal and cross-axis vestibulo-ocular
      reflex in the mouse.
AB  - One commonly observed phenomenon of vestibulo-ocular reflex (VOR) adaptation is a
      frequency-selective change in gain (eye velocity/head velocity) and phase
      (relative timing between the vestibular stimulus and response) based on the
      frequency content of the adaptation training stimulus. The neural mechanism
      behind this type of adaptation is not clear. Our aim was to determine whether
      there were other parameter-selective effects on VOR adaptation, specifically
      velocity-selective and acceleration-selective changes in the horizontal VOR gain
      and phase. We also wanted to determine whether parameter selectivity was also in
      place for cross-axis adaptation training (a visual-vestibular training stimulus
      that elicits a vestibular-evoked torsional eye movement during horizontal head
      rotations). We measured VOR gain and phase in 17 C57BL/6 mice during baseline (no
      adaptation training) and after gain-increase, gain-decrease and cross-axis
      adaptation training using a sinusoidal visual-vestibular (mismatch) stimulus with
      whole-body rotations (vestibular stimulus) with peak velocity 20 and 50 degrees
      /s both with a fixed frequency of 0.5 Hz. Our results show pronounced velocity
      selectivity of VOR adaptation. The difference in horizontal VOR gain after gain
      increase versus gain-decrease adaptation was maximal when the sinusoidal testing
      stimulus matched the adaptation training stimulus peak velocity. We also observed
      similar velocity selectivity after cross-axis adaptation training. Our data
      suggest that frequency selectivity could be a manifestation of both velocity and
      acceleration selectivity because when one of these is absent, e.g. acceleration
      selectivity in the mouse, frequency selectivity is also reduced. 

PMID- 24862509
TI  - Cyclic vomiting syndrome: treatment options.
AB  - Cyclic vomiting syndrome is a disorder characterized by recurrent episodes of
      severe nausea and vomiting separated by symptom-free periods. Our aims were to
      review treatments of adult cyclic vomiting syndrome as well as to identify areas
      for further clinical research and the unanswered questions in this field. We
      conducted a PubMed search using such keywords as "cyclic vomiting syndrome,"
      "nausea," "vomiting," "treatment," "trigger factors" and "tricyclic
      antidepressants" and combined this information with the knowledge and clinical
      research from the authors. Available data show that in adult cyclic vomiting
      syndrome, there is an impressive and sustained response to high-dose tricyclic
      antidepressants. In up to 13% who are regarded as poor responders to tricyclic
      antidepressants, a predictable profile can be identified related to coexisting
      psychological disorders, marijuana use, poorly controlled migraine headache or
      chronic narcotic use. Cyclic vomiting syndrome in adults is being an increasingly
      recognized entity. Tricyclic antidepressants are the main treatment for
      controlling symptoms. Eliminating and addressing trigger factors are an essential
      part of management.

PMID- 24862511
TI  - Overdiagnosis: how cancer screening can turn indolent pathology into illness.
AB  - The shift from illness to disease has had a profound impact on modern medicine -
      particularly in the realm of cancer screening. In screening, it is not patients
      with illness who seek help from the healthcare system; it is asymptomatic healthy
      individuals who are invited into the healthcare system to be examined for
      pathology. The underlying assumption of screening is that abnormalities and
      pathology always progress. If this were true, it would always make sense to look
      for disease even when people feel well. The million (or more accurately multi
      billion) dollar question is whether the fundamental assumption that disease
      invariably leads to illness is valid. This is the question that the present paper
      will try to explore and answer. 

PMID- 24862510
TI  - Embodied and disembodied allocentric simulation in high schizotypal subjects.
AB  - It is known that non-clinical subjects with high levels of schizotypal
      personality traits (High-S), as well as schizophrenic patients, have difficulties
      to judge how a scene would appear (so-called Appearance questions) from a point
      of view other than their own after having performed a disembodied perspective
      taking (D-PT, a mental self-rotation cued by an object like a chair). This
      inability has been defined allocentric simulation deficit. However, it is still
      unclear whether this inability might also regard an embodied transformation (E
      PT), which is a self-rotation cued by another individual in the scene, and
      whether the observed deficit regards the pure mental transformation phase. In the
      present study, we took advantage of a virtual reality environment to explore both
      embodied and disembodied allocentric simulation in healthy volunteers with low
      and high levels of schizotypal personality traits, as assessed by the Schizotypal
      Personality Questionnaire. All subjects performed a pure self-rotation cued by a
      chair (D-PT) or by an avatar (E-PT), or a control array rotation. Each rotation
      was followed by classical Appearance and Item questions. Results revealed no
      between-groups differences in the mental transformation phase, while High-S
      subjects were significantly slower than Low-S subjects in the Appearance task
      after D-PT, but not after E-PT. Accordingly, higher schizotypy levels (cognitive
      perceptual subscale) were positively correlated with slower reaction times in the
      Appearance task after D-PT. These data suggest the existence of a disembodied
      allocentric simulation deficit in non-clinical High-S, paving the way to future
      studies on clinical populations.

PMID- 24862507
TI  - Measuring the nausea-to-emesis continuum in non-human animals: refocusing on
      gastrointestinal vagal signaling.
AB  - Nausea and vomiting are ubiquitous as drug side effects and symptoms of disease;
      however, the systems that determine these responses are arguably designed for
      protection against food poisoning occurring at the level of the gastrointestinal
      (GI) tract. This basic biological pathway using GI vagal afferent communication
      to the brain is not well understood. Part of this lack of insight appears to be
      related to current experimental approaches, such as the use of experimental
      drugs, including systemic chemotherapy and brain penetrant agents, which activate
      parts of the nausea and vomiting system in potentially unnatural ways. Directly
      related to this issue is our ability to understand the link between nausea and
      vomiting, which are sometimes argued to be completely separate processes, with
      nausea as an unmeasurable response in animal models. An argument is made that
      nausea and emesis are the efferent limbs of a unified sensory input from the GI
      tract that is likely to be impossible to understand without more specific animal
      electrophysiological experimentation of vagal afferent signaling. The current
      paper provides a review on the use of animal models and approaches to defining
      the biological systems for nausea and emesis and presents a potentially testable
      theory on how these systems work in combination. 

PMID- 24862513
TI  - Logistic regression for dichotomized counts.
AB  - Sometimes there is interest in a dichotomized outcome indicating whether a count
      variable is positive or zero. Under this scenario, the application of ordinary
      logistic regression may result in efficiency loss, which is quantifiable under an
      assumed model for the counts. In such situations, a shared-parameter hurdle model
      is investigated for more efficient estimation of regression parameters relating
      to overall effects of covariates on the dichotomous outcome, while handling count
      data with many zeroes. One model part provides a logistic regression containing
      marginal log odds ratio effects of primary interest, while an ancillary model
      part describes the mean count of a Poisson or negative binomial process in terms
      of nuisance regression parameters. Asymptotic efficiency of the logistic model
      parameter estimators of the two-part models is evaluated with respect to ordinary
      logistic regression. Simulations are used to assess the properties of the models
      with respect to power and Type I error, the latter investigated under both
      misspecified and correctly specified models. The methods are applied to data from
      a randomized clinical trial of three toothpaste formulations to prevent incident
      dental caries in a large population of Scottish schoolchildren.

PMID- 24862512
TI  - A hybrid Bayesian hierarchical model combining cohort and case-control studies
      for meta-analysis of diagnostic tests: Accounting for partial verification bias.
AB  - To account for between-study heterogeneity in meta-analysis of diagnostic
      accuracy studies, bivariate random effects models have been recommended to
      jointly model the sensitivities and specificities. As study design and population
      vary, the definition of disease status or severity could differ across studies.
      Consequently, sensitivity and specificity may be correlated with disease
      prevalence. To account for this dependence, a trivariate random effects model had
      been proposed. However, the proposed approach can only include cohort studies
      with information estimating study-specific disease prevalence. In addition, some
      diagnostic accuracy studies only select a subset of samples to be verified by the
      reference test. It is known that ignoring unverified subjects may lead to partial
      verification bias in the estimation of prevalence, sensitivities, and
      specificities in a single study. However, the impact of this bias on a meta
      analysis has not been investigated. In this paper, we propose a novel hybrid
      Bayesian hierarchical model combining cohort and case-control studies and
      correcting partial verification bias at the same time. We investigate the
      performance of the proposed methods through a set of simulation studies. Two case
      studies on assessing the diagnostic accuracy of gadolinium-enhanced magnetic
      resonance imaging in detecting lymph node metastases and of adrenal fluorine-18
      fluorodeoxyglucose positron emission tomography in characterizing adrenal masses
      are presented.

PMID- 24862515
TI  - Foreword.

PMID- 24862514
TI  - Pharmacokinetics of buprenorphine following intravenous and buccal administration
      in cats, and effects on thermal threshold.
AB  - This study reports the pharmacokinetics of buprenorphine, following i.v. and
      buccal administration, and the relationship between buprenorphine concentration
      and its effect on thermal threshold. Buprenorphine (20 MUg/kg) was administered
      intravenously or buccally to six cats. Thermal threshold was determined, and
      arterial blood sampled prior to, and at various times up to 24 h following drug
      administration. Plasma buprenorphine concentration was determined using liquid
      chromatography/mass spectrometry. Compartment models were fitted to the time
      concentration data. Pharmacokinetic/pharmacodynamic models were fitted to the
      concentration-thermal threshold data. Thermal threshold was significantly higher
      than baseline 44 min after buccal administration, and 7, 24, and 104 min after
      i.v. administration. A two- and three-compartment model best fitted the data
      following buccal and i.v. administration, respectively. Following i.v.
      administration, mean +/- SD volume of distribution at steady-state (L/kg),
      clearance (mL.min/kg), and terminal half-life (h) were 11.6 +/- 8.5, 23.8 +/-
      3.5, and 9.8 +/- 3.5. Following buccal administration, absorption half-life was
      23.7 +/- 9.1 min, and terminal half-life was 8.9 +/- 4.9 h. An effect-compartment
      model with a simple effect maximum model best predicted the time-course of the
      effect of buprenorphine on thermal threshold. Median (range) ke0 and EC50 were
      0.003 (0.002-0.018)/min and 0.599 (0.073-1.628) ng/mL (i.v.), and 0.017 (0.002
      0.023)/min and 0.429 (0.144-0.556) ng/mL (buccal). 

PMID- 24862516
TI  - Effets perturbateurs endocriniens des pesticides organochlores.
AB  - Xenoestrogens such organochlorine pesticides are known to induce changes in
      reproductive development, function or behaviour in wildlife. Because these
      compounds are able to modify the estrogens metabolism, or to compete with
      estradiol for binding to the estrogen receptor, it may be possible that these
      products affect the risk of developing impaired fertility, precocious puberty or
      some kinds of cancer in man. Le plus ancien recit de lutte contre la pollution
      remonte a une legende indienne racontant que la divinite Sing-bonga etait
      incommodee par les emanations des fours dans lesquels les Asuras fondaient leurs
      metaux (1). Evidemment depuis, la problematique n-a cesse de s-accroitre et la
      contamination de la Terre par de nombreux polluants est devenue aujourd-hui un
      probleme majeur de notre Societe. La protection de notre environnement est une
      question capitale qui doit etre respectee malgre la pression economique actuelle
      et qui ne cessera de croitre au cours des prochaines annees meme si l
      identification objective et indiscutable de ce qui est essentiel - donc devant
      etre prioritairement garanti sur la planete - est difficile a cerner (2). " Un
      oiseau en mauvais etat ne pond pas de bons oeufs " disait un proverbe grec. Mais
      ce n-est qu-a partir de la seconde moitie du XXeme siecle que les toxicologues
      ont commence a identifier les effets qu-avaient entraines a l-echelle mondiale
      les pollutions emises aux XIXeme siecle sur la faune sauvage et sur le cheptel
      (3). L-histoire contemporaine des pesticides industriels commence vers 1874
      (synthese des organochlores) et se poursuit tout au long de ces 2 siecles en
      passant par la synthese des organophosphores (1950), des carbamates (1970) et des
      pyrethroides (1975) (4). Le dichlorodiphenyltrichloroethane (DDT) a ete
      synthetise pour la premiere fois par un etudiant en cours de preparation de sa
      these de doctorat : Othmer Zeidler. La production, reprise par les entreprises
      F.Mayo puis par la Geigy Co. a d-abord interesse l-armee, puis l-agriculture. Des
      la fin de la 2(eme) guerre mondiale, des mises en garde furent lancees a propos
      des effets nocifs du produit (4). Un declin des populations de grives, d-aigles
      chauves, d-orfaies et de mammiferes consommateurs de poissons fut constate a
      partir des annees 50 et denonce par Rachel Carson dans son celebre appel du "
      Silent Spring " de 1962. Bien qu-il soit interdit en Occident depuis les annees
      70, ce produit a ete tellement utilise et presente une remanence si longue qu-une
      contamination ubiquitaire existe aujourd-hui encore. De plus, ce produit continue
      a etre produit aux USA pour etre utilise a des fins de demoustification dans les
      pays en voie de developpement. Il en va de meme de l-Hexachlorobenzene (HCB), un
      autre organochlore dont l-usage est interdit sous nos latitudes, mais reste
      frequent dans d-autres pays. Ces deux exemples indiquent que le probleme de la
      contamination continue a nous concerner, meme pour des produits dont l-usage est
      aujourd-hui strictement reglemente ou interdit. Des effets sur la faune semblent
      encore actuellement devoir etre attribues a ces produits. La diminution de la
      population des phoques dans la mer de Wadden pourrait etre due a la forte
      contamination en composants organochlores des poissons dont ces phoques se
      nourrissent (5). Expose au DDT et a son metabolite
      dichlorodiphenyldichloroethylene (DDE), le Seratherodon mossambicus presente une
      reduction de la secretion de cortisol par une action toxique cytospecifique sur l
      axe hypothalamo-hypophysaire (6). Des travaux recents ont montre que le DDT et le
      DDE se lient chez les oiseaux et les mammiferes au moyen de liaisons covalentes
      aux cellules de la zona fasciculata - homologue du tissu interrenal du poisson -
      induisant des microhemorragies. Cette " defaillance " cortisolique peut s
      accompagner d-une perturbation du metabolisme glucidique et notamment d-un taux
      eleve de glycogene hepatique (7). Les pesticides organochlores (DDT, DDE)
      entrainent egalement des perturbations d-ordre metabolique chez certaines especes
      d-oiseaux, notamment le faucon pelerin en Grande Bretagne et les oiseaux
      piscivores des grands lacs nord americains ou l-on a constate au cours des annees
      1960 que leur reproduction etait menacee et qu-une des manifestations les plus
      evidentes des perturbations observees etait le taux eleve de malformations (8).
      Des mortalites elevees de poissons ou de coquillages ont ete rapportees dans des
      elevages situes a proximite des zones d-epandage de pesticides organophosphores
      et de carbamates. En 1991, la dispersion aerienne de fenitrothion dans le but de
      provoquer la demoustication en Languedoc a ete a l-origine de la perte de
      plusieurs tonnes de crevettes japonaises. L-utilisation de trichlorfon et de
      dichlorvos comme antiparasitaires dans des fermes d-elevages de saumons a
      provoque des episodes de mortalite importante (9). 

PMID- 24862517
TI  - Determination serique de la crimidine par clhp/es/sm chez un patient ayant ingere
      un " souricide foudroyant ".
AB  - Crimidine (2 chloro, 4 methyl, 6 dimethyl amidopyrine) is a synthetic rodenticide
      which causes acute poisonings after oral ingestion in human. Major toxic effects
      are consciousness disorders, hypertonic coma and convulsions. Toxic level in
      human is about 5 mg/Kg. An intoxication case is reported. Five serums collected
      at different times were analyzed with HPLC/ ES/MS. Crimidine was extracted with
      ethylacetate with recovery over 80 %. Linearity was up to 800 MUg/L. LOQ and LOD
      were 0.5 and 0.3 MUg/L respectively. The coefficients of variation were less than
      10 % for repeatability and reproductibility. Serum levels varied from 368 MUg/L
      for H0 to 64 MUg/L for H10 and elimination of crimidine was linear in time. 

PMID- 24862518
TI  - Intoxications par l'aldicarbe : revue des cas survenus dans le nord de la france
      entre 1998 et 2001.
AB  - Among the 2 726 cases of human pesticide poisoning collected at the Poison Centre
      of Lille from January 1998 to May 2001, 39 cases were related to the ingestion of
      aldicarb. Analysis of the circumstances found a suicide attempts in 33 cases and
      an accidental ingestion in 6 cases. The sex-ratio was 31 men for 8 women, mean
      age was of 36,6 years (15 months - 77 years). Thirty one poisoning were
      symptomatic with muscarinic signs (20 cases), digestive (15 cases), neurological
      ( 8 cases), nicotinic signs (6 cases). Treatment was based on digestive
      evacuation (14 cases), administration of activated charcoal (14 cases), atropine
      (7 cases), pralidoxime (1 case), preservative vital functions by intubation and
      ventilation (7 cases). Sedation was necessary in 4 cases. Hospitalization was
      necessary in 34 cases. The Poison Severity Score was estimated at 0 (any gravity)
      in 5 cases, 1 (weak) in 12 cases, 2 (moderate) in 7 cases, 3 (severe) in 8 cases
      and 4 (lethal) in 2 cases. In one of deaths, aldicarb was determined by HPLC-DAD
      in blood (6,04 MUg / ml), urines (1,88 MUg / ml) and gastric contents (3,98 MUg /
      ml). These concentrations are the most important ever described in the
      litterature. Aldicarb is the most toxic carbamate insecticide for human. 

PMID- 24862519
TI  - Determination des metabolites monoester de butylbenzyl-phthalate (bbp) par gcms
      dans les urines de personnes exposees: analysis of the monoester metabolites of
      butylbenzyl phthalate by gc-ms in urine of exposed workers.
AB  - A method of analysis was developed to determine free and glucuronated monobutyl
      phthalate (BuP) and monobenzyl phthalate (BeP) in urine for the assessment of
      exposure of man to butylbenzyl phthalate (BBP) in the workplace and in the
      environment. This method has also been applied in pharmacokinetic studies in
      experimental animals and the determination in urine of exposed workers. Urine
      samples are first subjected to enzymatic hydrolysis with beta-glucuronidase to
      enable the measurement of the total amount of monophthalates excreted. A fraction
      of the hydrolysate is used for further analysis. Monohexyl phthalate is added as
      an internal standard and the hydrolysed urine extracted with a n-hexane/
      dichloromethane mixture after acidification and saturation with salt. The organic
      fractions are washed, dehydrated and evaporated. The residue is methylated by
      means of diazomethane dissolved in diethylether, evaporated and further purified
      by extraction into n-hexane from an alkaline buffer. The organic fractions are
      evaporated and the residue redissolved in acetonitrile for analysis by ion trap
      GC-MS equipped with a 50 m apolar WCOT capillary column. TIC mass chromatograms
      are recorded from which SIM chromatograms can be derived electronically. The m/z
      values used are 91, 149, and 163 which provide a sufficient sensitive response
      and which are specific enough to pick up the methylated monophthalates under
      investigation. The quantitative limit of detection (LOQ) is 60 MUg/L for BuP and
      BeP when using the Magnum ion Trap detector and 3 MUg/L when using the Polaris Q
      in the splitless mode. The calibration curve in urine is linear from 120 MUg/L to
      50,000 MUg/L with a coefficient of variation of less than 10 % . In case of the
      Polaris Q linearity started from 10 MUg/L. The recovery of the method is
      monitored by the response signal of the internal standard in the ion
      chromatogram. In the event of insufficient recovery the analysis is repeated.
      Variations in recovery are compensated by the internal standard of which the
      molecular structure is very similar to the ones of the monophthalates under
      investigation. 

PMID- 24862520
TI  - Usage criminel de substances psycho-actives : le probleme de la duree de
      detection.
AB  - On a regular basis, the media presents the potential risks of the use of psycho
      active compounds, including misused pharmaceuticals (flunitrazepam, GHB) or drugs
      of abuse (cannabis, LSD, ecstasy). Ethanol is also frequently encountered. These
      drugs can be used for recreational purposes by addicts or can be observed after
      sexual assaults (drugs spiked in food). Forensic toxicology can be involved in
      several situations to document impairment, such as : crime under influence, date
      rape, driving under influence, phsychiatric disorders, determination of the cause
      of death ... In some particular situations, it can be very cautious to
      investigate exposure to psycho-active drugs, due to late sampling of biological
      specimens. To enhance the window of detection of 3 specific drugs, the authors
      propose the following : 1. Use of an ultra-sensitive technique, such as
      GC/MS/MS/NCI for 7-aminoflunitrazepam; 2. Use of a cumulative specimen, such as
      sweat for GHB and 3. Use of a metabolite with a long half-life, such as ethyl
      glucuronide for ethanol. 

PMID- 24862521
TI  - Ketamine - reves et realites.
AB  - Ketamine is an anaesthetic used in human medicine and veterinary practice,
      synthesised on 1962 and marketed on 1970 in France. Recreational uses were
      described during 1992 in the medical communauty and in 1996 in the dance
      settings. The chemical name of ketamine is 2 - (2chlorophenyl) 2-(methylamine)
      cyclohexanone, an aryl cyclohexylamine, structurally related to phencyclidine.
      Ketamine is known under the following street names : Keta K, Kate, Special K,
      Vitamine K, la Golden, la Veterinaire. Ketamine is used intranasally, orally and
      intramusculary in recreational use. Ketamine is manufactured by the chemical
      industry. Due to the complicated synthesis, it is sold illicitly for recreational
      use. Ketamine is a dissociative drug, and the user enters in a psychedelic dream
      with hallucinations, floating sensation, feeling of dissociation of the mind from
      the body. The dream is forgotten, the user fulls in reality with loss of self
      control, risk of acute intoxication. In long term exposure, tolerance,
      dependence, withdrawal signs and flash back are described. Ketamine trademarks
      are subject to control in France through medicine legislation Ketamine and its
      salts are subject to control under the national legislation on narcotics and
      psychotropics substance. From September 2001, the theft of medical and veterinary
      trademarks have to be declared to police, care health authority Pharmacy control
      authority and French Health Products Safety Agency. 

PMID- 24862522
TI  - Ma Huang, du complement alimentaire a l'abus.
AB  - Dietary supplements containing Ma Huang (chinease ephedra) are available on the
      web sites and dietary shops in USA. They are widely promoted and used as a mean
      of weight reduction and energy enhancement. They contain Ma Huang alone or
      combined with Guarana (caffeine), creatine, St Jonh's wort, carnitine and are
      proposed with different labels. Numerous reports of adverse reactions and acute
      intoxication related to these products use were described in the medical
      literature. In the light of the severity of these cases, some of which resulted
      in permanent injury and death, the Food and Drug Administration has proposed
      limits on the dose and duration of use of such supplements. A review of 140
      reports submitted to the FDA between June 1997 and March 1999, 47 % involved
      cardiovascular symptoms, 18 % neurological symptoms. Severe hypertension was the
      single most frequent adverse effect followed by tachycardia, myocardial
      infarction, stroke, seizure. Ten events resulted in death and 13 produced
      permanent impairment. In France, ampleness of the use of dietary supplements
      containing ephedra alkaloids is unknown. Two French recent severe poisonings (one
      with "ripped Fuel" for losing weight and the other with "Energy pills" in a body
      builder) show that there is serious health risks for the chronic users. Dietary
      supplements are not subject to control under "la Direction Generale de la Sante".
      Informations for general public, medical community and health-care authorities
      are necessary to be aware of potential health hazards of these products use. 

PMID- 24862524
TI  - Nouvelles drogues de " rave-parties " : ketamine et prolintane.
AB  - "Rave parties", all-night dance parties based on "techno" music, represent an
      increasing phenomenon in France. "Rave drugs" refers to a wide variety of drugs
      used by the young participants owing to their hallucinogenic or stimulant
      effects. Uncertainties about the sources of these substances, the possible
      contaminants and the multiplicity of the associations make it difficult to
      evaluate the toxic consequences that might be expected in this particular
      context. This report presents toxicological cases documented by analytical
      findings in which two pharmacological agents abused in "rave parties" in South
      West of France were found. The day following a party, a 17 year-old girl showed a
      confused state with drowsiness and hallucinations. She confessed having consumed
      a white powder sold as "ecstasy", that sample analysis identified as pure
      ketamine. Ketamine is an anaesthetic agent primarily used in veterinary medicine
      and paediatrics. This drug seems to be abused, mainly by the intranasal route,
      owing to its hallucinogen effects. Its used in "rave-party" appears to be marked
      by unsuspected consumption. All long another party, a large quantity of orange
      tablets were sold and abused by several participants. Analysis performed on some
      fragments of these tablets revealed the presence of prolintane and ascorbic acid.
      Prolintane, an amphetamine-related substance, is a central nervous system
      stimulant. This compound is "freely" available in Spain in combination with
      several vitamins, under the form of tablets with orange coating named "Katovit"
      and sold at low price: 1.93 ?/20 tablets (200 mg of prolintane). 

PMID- 24862523
TI  - Utilisation de l'acide gamma-hydroxybutyrique (ghb) dans les rave-parties et pour
      la soumission chimique en france : mythe ou realite?
AB  - Since many years gamma-hydroxybutyric acid (GHB) is presented as very popular in
      rave-parties and for bodybuilders. It seems to be a controversy between media
      coverage and the results of toxicological analysis done in high-level
      laboratories. In order to clarify this problem, we compiled the data of 6
      laboratories. They used the same analytical method by GC/MS. Depending the
      laboratory, the limit of detection was 1-2 MUg/mL and the limit of quantification
      was 2.5-5 MUg/ mL. Two labs where looking for GHB in each forensic case (100 and
      150 cases a year). Others labs performed GHB analysis only on specific request
      (each 10 cases a year). Mean time between ingestion of GHB and blood/urine
      sampling was 12-48 h. Mean time between sampling and analysis was much higher (a
      few hours to a few month. All samples were stored at +4 degrees C. Only 3 cases
      were considered as positive (blood GHB : 165, 132 and 114 MUg/mL, urine GHB :
      7450 and 436 MUg/ mL) They were admitted in an hospital EU. Interpreting results
      remains very difficult because GHB is endogenous, present in blood and urine, and
      its half-life is very short. One has to report only " positive " GHB results when
      amounts are higher than 5 MUg/mL in blood and 10 MUg/mL in urine. Obviously,
      forensic toxicologists have to play a very important part in diagnosis of GHB
      intoxications and estimating its frequency. Actually, because the lack of data in
      France, it is not possible to answer the question asked in the title of this
      paper. 

PMID- 24862525
TI  - Dosage rapide du propofol dans les matrices biologiques et les cheveux par hs
      gc/ms.
AB  - This paper proposes an original method for the determination of propofol in
      biological specimens. For example, hair specimens are cut into small pieces and
      incubated overnight in Soerensen buffer at 40 degrees C. After headspace
      preparation of the biological specimens spiked with tetrahydrofurane (internal
      standard), the analytes are transfered to the gas chromatograph and separated on
      a HP Wax capillary column. Detection is achieved in SIM mode (propofol : m/z 117,
      163 and 178) on a mass spectrometer operating in electronic impact mode. The
      developped procedure is easy (full-automated), rapid (no extraction- or
      derivatization-step), sensible and accurate. After validation of the analytical
      method (linearity, extraction recovery, repetability, limit of detection), this
      new procedure was applied to forensic cases. 

PMID- 24862526
TI  - Intoxication mortelle apres ingestion accidentelle de xylocaine visqueuse a 2%
      chez une jeune enfant.
AB  - We report a case of fatal intoxication with 2% viscous lidocaine. A 18 month old
      infant was admitted after malaise and cardiorespiratory arrest at home. He was
      resuscitated, then seizures appeared before arrival at the hospital. Treatment
      was symptomatic, including cardiorespiratory resuscitation and administration of
      anticonvulsants. Identification of lidocaine and its metabolite
      monoethylglycinexylidide (MEGX) MEGX was performed after organic extraction by
      High Performance Liquid Chromatography (HPLC) with Diode Array Detection (DAD);
      the serum concentrations, determined by Fluorescence Polarisation Immuno Assay
      (FPIA), were : 1,1 MUg / ml for lidocaine and 0,94 MUg / ml for MEGX (H+7) and
      0,30 MUg / ml for the lidocaine (Day+1). Neurotoxic manifestations appear at
      lower concentrations than cardiotoxic symptoms which are correlated with plasma
      levels of lidocaine. The toxic symptoms begin with headache, hallucinations,
      seizure, coma, respiratory arrest and circulatory collapse. The toxic symptoms
      can persist even after the decrease of lidocaine concentration under therapeutic
      levels. There is no antidote and acute lidocaine toxicity is managed with
      supportive therapy (diazepam for seizures, intubation, chronotropic agents).
      Considering the gravity of these poisonings which remain rare, the 2% viscous
      lidocaine prescription is forbidden for children under 6 years old. 

PMID- 24862527
TI  - Suicide with remifentanil and midazolam : a case report.
AB  - Background : Remifentanil (Ultiva(r)) is a recently introduced esterase
      metabolized potent opioid (EMO) MU-receptor agonist with a rapid onset and offset
      of action for use as part of general anaesthesia in association with isoflurane
      or propofol or with midazolam (Dormicum(r)) and in combination with mivacurium.
      Case Report : A nurse from the anaesthesiology department of a hospital was found
      dead at home with a syringe and empty vials of Ultiva(r) (2 mg) and of Dormicum
      (r) (1 mg/mL). At autopsy several injection sites were found on her body. Usual
      toxicology screening operated in our laboratory revealed only the presence of
      benzodiazepines in blood. Regarding the case history, we decided to adapt a
      method specially designed for remifentanil and its inactive metabolite testing.
      The analytes were isolated by SPE on a Clean-Screen column. After silylation with
      BSTFA with 1% TMCS, the analytes were detected by GC/MS-EI operating in the SIM
      mode. No Remifentanil could be detected, whereas the metabolite of remifentanil
      GR90291 was determined in femoral blood, liver, kidney and lung. Furthermore,
      midazolam could be detected in femoral and cardiac blood. Hair analysis of a
      segment of 5 cm revealed the presence of diazepam and midazolam, whereas neither
      remifentanil nor its metabolite could be detected. 

PMID- 24862528
TI  - Methemoglobinemie consecutive a l'abus de gel de lidocaine visqueuse.
AB  - Lidocaine use may lead to methemoglobinemia. Lidocaine is clinically widely used
      as an anaesthesic drug, however its toxic effect is rare. We report a high
      methemoglobinemia level of 31.1 % following repeated Xylocaine(r) gel oral
      applications. New metabolic pathways of lidocaine have been reported leading to
      dimethylphenylhydroxylamine in humans. This metabolism is very similar to the
      aniline derivative ones, and may explain lidocaine methemoglobinemia effect. 

PMID- 24862529
TI  - Spatial organization of transcription in bacterial cells.
AB  - Prokaryotic transcription has been extensively studied over the past half a
      century. However, there often exists a gap between the structural, mechanistic
      description of transcription obtained from in vitro biochemical studies, and the
      cellular, phenomenological observations from in vivo genetic studies. It is now
      accepted that a living bacterial cell is a complex entity; the heterogeneous
      cellular environment is drastically different from the homogenous, well-mixed
      situation in vitro. Where molecules are inside a cell may be important for their
      function; hence, the spatial organization of different molecular components may
      provide a new means of transcription regulation in vivo, possibly bridging this
      gap. In this review, we survey current evidence for the spatial organization of
      four major components of transcription [genes, transcription factors, RNA
      polymerase (RNAP) and RNAs] and critically analyze their biological significance.

PMID- 24862530
TI  - Differences in behavior of tube current modulation techniques for thoracic CT
      examinations between male and female anthropomorphic phantoms.
AB  - Our objective was to investigate the differences in behavior of tube current
      modulation (TCM) techniques for thoracic CT examinations between male and female
      anthropomorphic phantoms. The phantoms were scanned with an automatic exposure
      control system in the longitudinal (z-) and angular-longitudinal (xyz-) TCM, in
      addition to the fixed-mA which was used as a reference. Axial dose distributions
      were measured at the levels of the breasts and the diaphragm, and longitudinal
      dose distributions were measured from the thoracic-inlet level to the diaphragm
      level at the center and periphery of the phantoms by use of eight solid-state
      detectors. Image noise was quantitatively measured continuously from the top to
      the bottom images of the phantoms. With the male phantom, the percentage of
      average absorbed dose with the xyz-TCM mode compared to the z-TCM mode was 90.2 %
      at the level of the nipples. This value was significantly smaller than that for
      the female phantom (95.6 %, P < 0.0001). With either phantom, the percentage of
      absorbed doses in the longitudinal direction with the xyz-TCM mode compared to
      the z-TCM mode at the center of the phantom was almost the same as the percent
      ratio at the periphery of the phantom. Therefore, the effect of xyz-TCM was less
      pronounced with the female phantom, especially on the reduction of the breast
      dose. The increase of image noise at the level of the supraclavicular fossa (in
      the male phantom) and at the level of the diaphragm (both phantoms) could not be
      avoided with the use of TCM techniques.

PMID- 24862532
TI  - Liquid-solid interfaces: structure and dynamics from spectroscopy and
      simulations.

PMID- 24862531
TI  - Involvement of C2H2 zinc finger proteins in the regulation of epidermal cell fate
      determination in Arabidopsis.
AB  - Cell fate determination is a basic developmental process during the growth of
      multicellular organisms. Trichomes and root hairs of Arabidopsis are both readily
      accessible structures originating from the epidermal cells of the aerial tissues
      and roots respectively, and they serve as excellent models for understanding the
      molecular mechanisms controlling cell fate determination and cell morphogenesis.
      The regulation of trichome and root hair formation is a complex program that
      consists of the integration of hormonal signals with a large number of
      transcriptional factors, including MYB and bHLH transcriptional factors. Studies
      during recent years have uncovered an important role of C2H2 type zinc finger
      proteins in the regulation of epidermal cell fate determination. Here in this
      minireview we briefly summarize the involvement of C2H2 zinc finger proteins in
      the control of trichome and root hair formation in Arabidopsis. 

PMID- 24862533
TI  - HTA agencies facing model biases: the case of type 2 diabetes.
AB  - When evaluating new drugs or treatments eligible for reimbursement, health
      technology assessment (HTA) agencies are repeatedly faced with cost-effectiveness
      analyses that evidence lack of adequate data and modeling biases. The case of
      type 2 diabetes illustrates this difficulty. In spite of its high disease burden,
      type 2 diabetes is poorly documented through existing cost-effectiveness
      analyses. We support this statement by an exhaustive literature review that
      enables us to precisely pinpoint the limitations of models used for the
      assessment of newly marketed (and expensive) drugs. We find that models are
      mostly restricted to surrogate endpoints and based on non-inferiority clinical
      trial data; they also show biases in the choice of comparators and inclusion
      criteria. Such limitations undermine the scope and applicability of HTA practice
      guidelines based on cost-effectiveness evidence. Nevertheless, cost-effectiveness
      models remain an opportunity to better inform decision makers and to reduce the
      uncertainty surrounding their decisions. HTA agencies are best placed to provide
      incentives for companies to improve the quality of the cost-effectiveness studies
      submitted for pricing and reimbursement decisions. One such incentive is to
      include stages of discussion between the company and the health authority during
      the evaluation process. 

PMID- 24862534
TI  - Peripheral nerve block and local anaesthetic dose, how much is enough?

PMID- 24862535
TI  - Hardness gradients of dual-polymerized flowable composite resins in simulated
      root canals.
AB  - STATEMENT OF PROBLEM: Information is lacking of the polymerization depth of dual
      polymerized flowable composite resin foundation materials in simulated root
      canals. PURPOSE: The purpose of this study was to investigate the hardness
      gradients and the polymerization depth of dual-polymerized flowable composite
      resin foundation materials in simulated root canals. MATERIAL AND METHODS: Slots
      in steel split cylinders with 1 open end were filled with the following 6
      materials: Luxa Core, Para Core, Clearfil DC Core, Multi Core Flow, Gradia Core,
      and Core-Flo DC. After filling, they were subjected to a light intensity of 1250
      mWcm(-2) with a light-emitting diode light through their open ends for 20
      seconds. The resulting specimens were stored in a light-proof box at 37 degrees
      C, and the Knoop hardness gradients of each polymerized material were measured
      after 0.5 hour, 24 hours, and 120 hours. The surface readings were obtained in 1
      mm intervals at 1 mm to 10 mm away from the open ends. The collected data were
      analyzed by 2-way ANOVA and the Student-Newman-Keuls test (alpha=.05). RESULTS:
      Before the Knoop hardness numbers of the 6 materials became stable, they
      decreased gradually in depth at each time point (P<.001). However, the depths at
      which they became stable differed. The Knoop hardness numbers of Luxa Core and
      Core-Flo DC reached stability at a depth of 3 mm, Para Core at 4 mm, and Clearfil
      DC Core, Multi Core Flow, and Gradia Core at 5 mm. Additionally, at 120 hours
      after exposure, the ratios of the Knoop hardness numbers at a depth of 5 mm to
      those at 1 mm were 63.08% for Luxa Core, 70.48% for Clearfil DC Core, 81.38% for
      Para Core, 80.49% for Gradia Core, 86.30% for Multi Core Flow, and 96.28% for
      Core-Flo DC. CONCLUSIONS: In simulated root canals, the flowable composite resin
      foundation materials tested had better polymerization under dual polymerizing
      than under chemical polymerizing, and their chemical-polymerized capabilities
      could determine the definitive polymerization depth.

PMID- 24862536
TI  - Axitinib Improves Radiotherapy in Murine Xenograft Lung Tumors.
AB  - A third of patients with non-small cell lung cancer (NSCLC) present with un
      resectable stage III locally advanced disease and are currently treated by chemo
      radiotherapy but the median survival is only about 21months. Using an orthotopic
      xenograft model of lung carcinoma, we have investigated the combination of
      radiotherapy with the anti-angiogenic drug axitinib (AG-013736, Pfizer), which is
      a small molecule receptor tyrosine kinase inhibitor that selectively targets the
      signal transduction induced by VEGF binding to VEGFR receptors. We have tested
      the combination of axitinib with radiotherapy in nude mice bearing human NSCLC
      A549 lung tumors. The therapy effect was quantitatively evaluated in lung tumor
      nodules. The modulation of radiation-induced pneumonitis, vascular damage and
      fibrosis by axitinib was assessed in lung tissue. Lung irradiation combined with
      long-term axitinib treatment was safe resulting in minimal weight loss and no
      vascular injury in heart, liver and kidney tissues. A significant decrease in the
      size of lung tumor nodules was observed with either axitinib or radiation,
      associated with a decrease in Ki-67 staining and a heavy infiltration of
      inflammatory cells in tumor nodules. The lungs of mice treated with radiation and
      axitinib showed a complete response with no detectable residual tumor nodules. A
      decrease in pneumonitis, vascular damage and fibrosis were observed in lung
      tissues from mice treated with radiation and axitinib. Our studies suggest that
      axitinib is a potent and safe drug to use in conjunction with radiotherapy for
      lung cancer that could also act as a radioprotector for lung tissue by reducing
      pneumonitis and fibrosis.

PMID- 24862537
TI  - Promoted Growth of Brain Tumor by the Transplantation of Neural Stem/Progenitor
      Cells Facilitated by CXCL12.
AB  - The targeted migration of neural stem/progenitor cells (NSPCs) is a prerequisite
      for the use of stem cell therapy in the treatment of pathologies. This migration
      is regulated mainly by C-X-C motif chemokine 12 (CXCL12). Therefore, promotion of
      the migratory responses of grafted cells by upregulating CXCL12 signaling has
      been proposed as a strategy for improving the efficacy of such cell therapies.
      However, the effects of this strategy on brain tumors have not yet been examined
      in vivo. The aim of the present study was thus to elucidate the effects of
      grafted rat green fluorescent protein (GFP)-labeled NSPCs (GFP-NSPCs) with CXCL12
      enhancement on a model of spontaneous rat brain tumor induced by N-ethyl-N
      nitrosourea. T2-weighted magnetic resonance imaging was applied to determine the
      changes in tumor volume and morphology over time. Postmortem histology was
      performed to confirm the tumor pathology, expression levels of CXCL12 and C-X-C
      chemokine receptor type 4, and the fate of GFP-NSPCs. The results showed that the
      tumor volume and hypointense areas of T2-weighted images were both significantly
      increased in animals treated with combined NSPC transplantation and CXCL12
      induction, but not in control animals or in those with tumors that received only
      one of the treatments. GFP-NSPCs appear to migrate toward tumors with CXCL12
      enhancement and differentiate uniquely into a neuronal lineage. These findings
      suggest that CXCL12 is an effective chemoattractant that facilitates exogenous
      NSPC migration toward brain tumors and that CXCL12 and NSPC can act
      synergistically to promote tumor progression with severe hemorrhage.

PMID- 24862539
TI  - Addition of lomustine for bevacizumab-refractory recurrent glioblastoma.

PMID- 24862538
TI  - Uptake of [18F]EF5 as a Tracer for Hypoxic and Aggressive Phenotype in
      Experimental Head and Neck Squamous Cell Carcinoma.
AB  - PURPOSE: This study aims to investigate whether the uptake of 2-(2-nitro-1H
      imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)-acetamide ([18F]EF5) and 2-deoxy-2
      [18F]fluoro-d-glucose ([18F]FDG) is associated with a hypoxia-driven adverse
      phenotype in head and neck squamous cell carcinoma cell lines and tumor
      xenografts. METHODS: Xenografts were imaged in vivo, and tumor sections were
      stained for hypoxia-inducible factor 1alpha (Hif-1alpha), carbonic anhydrase IX
      (CA IX), and glucose transporter 1 (Glut-1). Tracer uptakes and the expression of
      Hif-1alpha were determined in cell lines under 1% hypoxia. RESULTS: High [18F]EF5
      uptake was seen in xenografts expressing high levels of CA IX, Glut-1, and Hif
      1alpha, whereas low [18F]EF5 uptake was detected in xenografts expressing low
      amounts of CA IX and Hif-1alpha. The uptake of [18F]EF5 between cell lines varied
      extensively under normoxic conditions. A clear correlation was found between the
      expression of Hif-1alpha and the uptake of [18F]FDG during hypoxia. CONCLUSIONS:
      The UT-SCC cell lines studied differed with respect to their hypoxic phenotypes,
      and these variations were detectable with [18F]EF5. Acute hypoxia increases
      [18F]FDG uptake in vitro, whereas a high [18F]EF5 uptake reflects a more complex
      phenotype associated with hypoxia and an aggressive growth pattern.

PMID- 24862540
TI  - Recombinant production and film properties of full-length hornet silk proteins.
AB  - Full-length versions of the four main components of silk cocoons of Vespa
      simillima hornets, Vssilk1-4, were produced as recombinant proteins in
      Escherichia coli. In shake flasks, the recombinant Vssilk proteins yielded 160
      330mg recombinant proteinl(-1). Films generated from solutions of single Vssilk
      proteins had a secondary structure similar to that of films generated from native
      hornet silk. The films made from individual recombinant hornet silk proteins had
      similar or enhanced mechanical performance compared with films generated from
      native hornet silk, possibly reflecting the homogeneity of the recombinant
      proteins. The pH-dependent changes in zeta (zeta) potential of each Vssilk film
      were measured, and isoelectric points (pI) of Vssilk1-4 were determined as 8.9,
      9.1, 5.0 and 4.2, respectively. The pI of native hornet silk, a combination of
      the four Vssilk proteins, was 4.7, a value similar to that of Bombyx mori
      silkworm silk. Films generated from Vssilk1 and 2 had net positive charge under
      physiological conditions and showed significantly higher cell adhesion activity.
      It is proposed that recombinant hornet silk is a valuable new material with
      potential for cell culture applications. 

PMID- 24862541
TI  - Surviving the surf: the tribomechanical properties of the periostracum of Mytilus
      sp.
AB  - We investigated the friction and wear behavior as well as the mechanical
      properties of the periostracum of Mytilus sp. Tribological properties were
      determined with a reciprocal sliding microtribometer, while mechanical
      characterization was performed using a nanoindenter. Measurements were performed
      in dry and wet conditions. On the dry periostracum we found a low friction
      coefficient of 0.078+/-0.007 on the young parts and a higher one of 0.63+/-0.02
      on the old parts of the shell. Under wet, saline, conditions we only observed one
      average coefficient of friction of 0.37+/-0.01. Microscopic ex situ analysis
      indicated that dry periostracum wore rather rapidly by plowing and fatigue, while
      it exhibited a high wear resistance when immersed in salt water. The Young's
      modulus and hardness of the periostracum were also investigated in both dry and
      wet conditions. Under dry conditions the Young's modulus of the periostracum was
      8+/-3GPa, while under wet conditions it was 0.21+/-0.05GPa. The hardness of dry
      periostracum samples was 353+/-127MPa, whereas the hardness of wet samples was
      5+/-2MPa. It was found that, in the wet state, viscous behavior plays a
      significant role in the mechanical response of the periostracum. Our results
      strongly indicate that the periostracum can provide an important contribution to
      the overall wear resistance of Mytilus sp. shell. 

PMID- 24862543
TI  - Atomic layer deposited gallium oxide buffer layer enables 1.2 V open-circuit
      voltage in cuprous oxide solar cells.
AB  - The power conversion efficiency of solar cells based on copper (I) oxide (Cu2 O)
      is enhanced by atomic layer deposition of a thin gallium oxide (Ga2 O3 ) layer.
      By improving band-alignment and passivating interface defects, the device
      exhibits an open-circuit voltage of 1.20 V and an efficiency of 3.97%, showing
      potential of over 7% efficiency. 

PMID- 24862544
TI  - Inaccuracies in oral cavity-pharynx cancer coded as the underlying cause of death
      on U.S. death certificates, and trends in mortality rates (1999-2010).
AB  - OBJECTIVE: To enhance surveillance of mortality from oral cavity-pharynx cancer
      (OCPC) by considering inaccuracies in the cancer site coded as the underlying
      cause of death on death certificates vs. cancer site in a population-based cancer
      registry (as the gold standard). METHODS: A database was used for 9 population
      based cancer registries of the Surveillance, Epidemiology and End Results (SEER)
      Program, including deaths in 1999-2010 for patients diagnosed in 1973-2010.
      Numbers of deaths and death rates for OCPC in the SEER population were modified
      for apparent inaccuracies in the cancer site coded as the underlying cause of
      death. RESULTS: For age groups <65 years, deaths from OCPC were underestimated by
      22-35% by using unmodified (vs. modified) numbers, but temporal declines in death
      rates were still evident in the SEER population and were similar to declines
      using routine mortality data for the entire U.S. population. Deaths were
      underestimated by about 70-80% using underlying cause for tonsillar cancers,
      strongly associated with human papillomavirus (HPV) infection, but a lack of
      decline in death rates was still evident. CONCLUSION: Routine mortality
      statistics based on underlying cause of death underestimate OCPC deaths but
      demonstrate trends in OCPC death rates that require continued surveillance in
      view of increasing incidence rates for HPV-related OCPC.

PMID- 24862546
TI  - [Management of disorders of sex development: current dilemmas].

PMID- 24862542
TI  - Phagocyte-myocyte interactions and consequences during hypoxic wound healing.
AB  - Myocardial infarction (MI), secondary to atherosclerotic plaque rupture and
      occlusive thrombi, triggers acute margination of inflammatory neutrophils and
      monocyte phagocyte subsets to the damaged heart, the latter of which may give
      rise briefly to differentiated macrophage-like or dendritic-like cells. Within
      the injured myocardium, a primary function of these phagocytic cells is to remove
      damaged extracellular matrix, necrotic and apoptotic cardiac cells, as well as
      immune cells that turn over. Recognition of dying cellular targets by phagocytes
      triggers intracellular signaling, particularly in macrophages, wherein cytokines
      and lipid mediators are generated to promote inflammation resolution, fibrotic
      scarring, angiogenesis, and compensatory organ remodeling. These actions
      cooperate in an effort to preserve myocardial contractility and prevent heart
      failure. Immune cell function is modulated by local tissue factors that include
      secreted protease activity, oxidative stress during clinical reperfusion, and
      hypoxia. Importantly, experimental evidence suggests that monocyte function and
      phagocytosis efficiency is compromised in the setting of MI risk factors,
      including hyperlipidemia and ageing, however underlying mechanisms remain
      unclear. Herein we review seminal phagocyte and cardiac molecular factors that
      lead to, and culminate in, the recognition and removal of dying injured
      myocardium, the effects of hypoxia, and their relationship to cardiac infarct
      size and heart healing. 

PMID- 24862547
TI  - Diabetes-induced increase of renal medullary hydrogen peroxide and urinary
      angiotensinogen is similar in normotensive and hypertensive rats.
AB  - AIMS: Activation of renal renin-angiotensin system (RAS) and reactive oxygen
      species (ROS) are the main pathophysiological mechanisms associated with kidney
      injury both in diabetes and hypertension. However, the contribution to medullary
      damage when the two pathologies coexist has seldom been explored. MAIN METHODS:
      Diabetes was induced with streptozotocin in twelve week-old male Wistar and
      spontaneously hypertensive rats (SHR) rats; controls received vehicle. Three
      weeks later, systolic blood pressure (SBP), plasma and urinary angiotensinogen
      (AGT), renal oxidative stress and metabolic status were evaluated. KEY FINDINGS:
      SBP was higher in SHR-controls than in Wistar-controls (200+/-6 and 127+/-3mmHg,
      respectively) and decreased in SHR-diabetics but not in Wistar-diabetics (143+/-8
      and 122+/-6mmHg, respectively). Renal medullary hydrogen peroxide (H2O2)
      production was similarly increased in diabetics (Wistar: 0.32+/-0.04 and 1.11+/
      0.10nmol/mg protein, respectively; SHR: 0.40+/-0.05 and 0.90+/-0.14nmol/mg
      protein, respectively) and positively correlated with glycemia (Wistar: r=0.7166,
      SHR: r=0.7899, p<0.05) and urinary AGT excretion (Wistar: r=0.8333; SHR:
      r=0.8326, p<0.05). Cortical H2O2 production was higher in SHR-controls than in
      Wistar-controls (1.10+/-0.09 and 0.26+/-0.04nmol/mg protein, respectively) and
      diabetes induction decreased it in SHR (0.70+/-0.09nmol/mg protein). Diabetes
      increased urinary AGT excretion by more than 7-fold and decreased plasma AGT
      concentration by more than 1.5-fold in both strains. SIGNIFICANCE: Our results
      show that STZ-induced diabetes increases medullary H2O2 production and urinary
      AGT excretion with similar magnitude in normotensive and hypertensive animals.
      Reducing blood pressure attenuates hypertension-associated cortical damage but
      does not prevent medullary dysfunction.

PMID- 24862545
TI  - Real-time intraoperative detection of breast cancer using near-infrared
      fluorescence imaging and Methylene Blue.
AB  - BACKGROUND: Despite recent developments in preoperative breast cancer imaging,
      intraoperative localization of tumor tissue can be challenging, resulting in
      tumor-positive resection margins during breast conserving surgery. Based on
      certain physicochemical similarities between Technetium((99m)Tc)-sestamibi
      (MIBI), an SPECT radiodiagnostic with a sensitivity of 83-90% to detect breast
      cancer preoperatively, and the near-infrared (NIR) fluorophore Methylene Blue
      (MB), we hypothesized that MB might detect breast cancer intraoperatively using
      NIR fluorescence imaging. METHODS: Twenty-four patients with breast cancer,
      planned for surgical resection, were included. Patients were divided in 2
      administration groups, which differed with respect to the timing of MB
      administration. N = 12 patients per group were administered 1.0 mg/kg MB
      intravenously either immediately or 3 h before surgery. The mini-FLARE imaging
      system was used to identify the NIR fluorescent signal during surgery and on post
      resected specimens transferred to the pathology department. Results were
      confirmed by NIR fluorescence microscopy. RESULTS: 20/24 (83%) of breast tumors
      (carcinoma in N = 21 and ductal carcinoma in situ in N = 3) were identified in
      the resected specimen using NIR fluorescence imaging. Patients with non
      detectable tumors were significantly older. No significant relation to receptor
      status or tumor grade was seen. Overall tumor-to-background ratio (TBR) was 2.4
      +/- 0.8. There was no significant difference between TBR and background signal
      between administration groups. In 2/4 patients with positive resection margins,
      breast cancer tissue identified in the wound bed during surgery would have
      changed surgical management. Histology confirmed the concordance of fluorescence
      signal and tumor tissue. CONCLUSIONS: This feasibility study demonstrated an
      overall breast cancer identification rate using MB of 83%, with real-time
      intraoperative guidance having the potential to alter patient management.

PMID- 24862549
TI  - The genetics of lissencephaly.
AB  - Lissencephaly is a spectrum of severe brain malformations caused by the failure
      of migrating neurons to reach optimal positions in the developing cerebral
      cortex. Several syndromes associated with lissencephaly have been characterized
      in recent years. Identification of the genetic basis of these disorders has
      brought fascinating insights into the mechanisms of brain development, as well as
      benefits to patients through improved molecular diagnosis and genetic counseling.
      This review explores the clinical presentation, radiological features,
      histological findings and molecular basis of lissencephaly with the aim of
      facilitating the selection and interpretation of gene tests in patients with
      'smooth brain' phenotypes.

PMID- 24862550
TI  - Nucleotide-binding oligomerization domain 1 regulates Porphyromonas gingivalis
      induced vascular cell adhesion molecule 1 and intercellular adhesion molecule 1
      expression in endothelial cells through NF-kappaB pathway.
AB  - BACKGROUND AND OBJECTIVE: Porphyromonas gingivalis has been shown to actively
      invade endothelial cells and induce vascular cell adhesion molecule 1 (VCAM-1)
      and intercellular adhesion molecule 1 (ICAM-1) overexpression. Nucleotide-binding
      oligomerization domain 1 (NOD1) is an intracellular pattern recognition reporter,
      and its involvement in this process was unknown. This study focused on
      endothelial cells infected with P. gingivalis, the detection of NOD1 expression
      and the role that NOD1 plays in the upregulation of VCAM-1 and ICAM-1. MATERIAL
      AND METHODS: The human umbilical vein endothelial cell line (ECV-304) was
      intruded by P. gingivalis W83, and cells without any treatment were the control
      group. Expression levels of NOD1, VCAM-1, ICAM-1, phosphorylated P65 between
      cells with and without treatment on both mRNA and protein levels were compared.
      Then we examined whether mesodiaminopimelic acid (NOD1 agonist) could increase
      VCAM-1 and ICAM-1 expression, meanwhile, NOD1 gene silence by RNA interference
      could reduce VCAM-1, ICAM-1 and phosphorylated P65 release. At last, we examined
      whether inhibition of NF-kappaB by Bay117082 could reduce VCAM-1 and ICAM- 1
      expression. The mRNA levels were measured by real-time polymerase chain reaction,
      and protein levels by western blot or electrophoretic mobility shift assays (for
      phosphorylated P65). RESULTS: P. gingivalis invasion showed significant
      upregulation of NOD1, VCAM-1 and ICAM-1. NOD1 activation by meso-diaminopimelic
      acid increased VCAM-1 and ICAM-1 expression, and NOD1 gene silence reduced VCAM-1
      and ICAM-1 release markedly. The NF-kappaB signaling pathway was activated by P.
      gingivalis, while NOD1 gene silence decreased the activation of NF-kappaB.
      Moreover, inhibition of NF-kappaB reduced VCAM-1 and ICAM-1 expression induced by
      P. gingivalis in endothelial cells. CONCLUSION: The results revealed that P.
      gingivalis induced NOD1 overexpression in endothelial cells and that NOD1 played
      an important role in the process of VCAM-1 and ICAM-1 expression in endothelial
      cells infected with P. gingivalis through the NF-kappaB signaling pathway.

PMID- 24862548
TI  - Sex pheromone biosynthetic pathways are conserved between moths and the butterfly
      Bicyclus anynana.
AB  - Although phylogenetically nested within the moths, butterflies have diverged
      extensively in a number of life history traits. Whereas moths rely greatly on
      chemical signals, visual advertisement is the hallmark of mate finding in
      butterflies. In the context of courtship, however, male chemical signals are
      widespread in both groups although they likely have multiple evolutionary
      origins. Here, we report that in males of the butterfly Bicyclus anynana,
      courtship scents are produced de novo via biosynthetic pathways shared with
      females of many moth species. We show that two of the pheromone components that
      play a major role in mate choice, namely the (Z)-9-tetradecenol and hexadecanal,
      are produced through the activity of a fatty acyl Delta11-desaturase and two
      specialized alcohol-forming fatty acyl reductases. Our study provides the first
      evidence of conservation and sharing of ancestral genetic modules for the
      production of FA-derived pheromones over a long evolutionary timeframe thereby
      reconciling mate communication in moths and butterflies. 

PMID- 24862551
TI  - Student attitudes towards clinical teaching resources in complementary medicine:
      a focus group examination of Australian naturopathic medicine students.
AB  - BACKGROUND: Complementary medicine is forming an increasingly large part of
      health care in developed countries and is increasingly being formally taught in
      tertiary academic settings. OBJECTIVES: An exploratory study of naturopathic
      student perceptions of, use of and attitudes towards teaching resources in
      naturopathic clinical training and education. METHODS: Focus groups were
      conducted with current and recent students of 4-year naturopathic degree
      programmes in Brisbane and Sydney to ascertain how they interact with clinical
      teaching materials, and their perceptions and attitudes towards teaching
      materials in naturopathic education. RESULTS: Naturopathic students have a
      complex and critical relationship with their learning materials. Although
      naturopathic practice is often defined by traditional evidence, students want
      information that both supports and is critical of traditional naturopathic
      practices, and focuses heavily on evidence-based medicine. Students remain
      largely ambivalent about new teaching technologies and would prefer that these
      develop organically as an evolution from printed materials, rather than depart
      from dramatically and radically from these previously established materials.
      CONCLUSIONS: Findings from this study will assist publishers, librarians and
      academics develop clinical information sources that appropriately meet student
      expectations and support their learning requirements.

PMID- 24862552
TI  - Disease mongering.

PMID- 24862553
TI  - Simple but precise engineering of functional nanocapsules through
      nanoprecipitation.
AB  - A general, rapid, and undemanding method to generate at will functional oil
      filled nanocapsules through nanoprecipitation is reported. On the basis of
      polymer and hexadecane/water/acetone phase diagrams, the composition can be set
      so that polymer chains preferentially stick at the interface of the oil droplets
      to create nanocapsules. The nanocapsules can be decorated with biorelevant
      molecules (biotin, fluorescent tags, metal nanoparticles) within the shell and
      loaded with hydrophobic molecules in a simple one-pot procedure. 

PMID- 24862554
TI  - Spatial patterns of Aquificales in deep-sea vents along the Eastern Lau Spreading
      Center (SW Pacific).
AB  - The microbial diversity associated with actively venting deep-sea hydrothermal
      deposits is tightly connected to the geochemistry of the hydrothermal fluids.
      Although the dominant members of these deposits drive the structure of the
      microbial communities, it is less well understood whether the lower abundance
      groups are as closely connected to the geochemical milieu, or driven perhaps by
      biotic factors such as microbial community interactions. We used the natural
      geochemical gradients that exist in the back-arc basin, Eastern Lau Spreading
      Center and Valu-Fa Ridge (ELSC/VFR) in the Southwestern Pacific, to explore
      whether the chemolithotrophic Aquificales are influenced by geographical
      location, host-rock of the vent field or deposit type. Using a combination of
      cloning, DNA fingerprinting (DGGE) and enrichment culturing approaches, all
      genera of this order previously described at marine vents were detected, i.e.,
      Desulfurobacterium, Thermovibrio, Aquifex, Hydrogenivirga, Persephonella and
      Hydrogenothermus. The comparison between clone libraries and DGGE showed similar
      patterns of distribution of different Aquificales whereas results differed for
      the enrichment cultures that were retrieved. However, the use of cultivation
      based and -independent methods did provide complementary phylogenetic diversity
      overview of the Aquificales in these systems. Together, this survey revealed that
      the ELSC/VFR contains some of the largest diversity of Aquificales ever reported
      at a deep-sea vent area, that the diversity patterns are tied to the geography
      and geochemistry of the system, and that this geochemical diverse back-arc basin
      may harbor new members of the Aquificales. 

PMID- 24862555
TI  - Independent, additive effects of five dietary variables on ad libitum energy
      intake in a residential study.
AB  - OBJECTIVE: To examine the relationship between dietary characteristics of self
      selected foods and energy balance in a cafeteria-style dining hall. METHODS: Ad
      libitum dietary intake from a self-selection menu was measured over two days in
      151 adults (70% female, mean age 41 years, mean BMI 24.9 kg/m(2) ). The
      associations of dietary variables with energy balance (calculated as measured
      energy intake/predicted energy requirements, pER) were assessed. RESULTS:
      Measured energy intake was significantly correlated with pER (R(2) =0.83, P <
      0.001). In mixed multiple regression models, percent energy from protein was
      negatively associated with energy balance (R(2) =0.04, P = 0.02), and percent
      energy from liquid sources (R(2)  = 0.02, P = 0.05), total dietary variety in
      females (R(2)  = 0.39, P < 0.001), and energy density (R(2)  = 0.57, P < 0.001)
      were positively associated with energy balance. In addition, glycemic index was
      inversely associated with energy balance in normal-weight individuals (R(2)  =
      0.14, P < 0.001) but not in overweight or obese individuals. CONCLUSIONS: There
      are independent associations of dietary protein, liquid calories, energy density,
      dietary variety, and glycemic index with energy balance, indicating additive
      effects of these dietary factors on energy intake and energy balance.
      Intervention studies are needed to determine whether dietary prescriptions
      combining these dietary factors facilitate long-term prevention of weight gain.

PMID- 24862556
TI  - Hebbian learning from higher-order correlations requires crosstalk minimization.
AB  - Activity-dependent synaptic plasticity should be extremely connection specific,
      though experiments have shown it is not, and biophysics suggests it cannot be.
      Extreme specificity (near-zero "crosstalk") might be essential for unsupervised
      learning from higher-order correlations, especially when a neuron has many
      inputs. It is well known that a normalized nonlinear Hebbian rule can learn
      "unmixing" weights from inputs generated by linearly combining independently
      fluctuating nonGaussian sources using an orthogonal mixing matrix. We previously
      reported that even if the matrix is only approximately orthogonal, a nonlinear
      specific Hebbian rule can usually learn almost correct unmixing weights (Cox and
      Adams in Front Comput Neurosci 3: doi: 10.3389/neuro.10.011.2009 2009). We also
      reported simulations that showed that as crosstalk increases from zero, the
      learned weight vector first moves slightly away from the crosstalk-free direction
      and then, at a sharp threshold level of inspecificity, jumps to a completely
      incorrect direction. Here, we report further numerical experiments that show that
      above this threshold, residual learning is driven instead almost entirely by
      second-order input correlations, as occurs using purely Gaussian sources or a
      linear rule, and any amount of crosstalk. Thus, in this "ICA" model learning from
      higher-order correlations, required for unmixing, requires high specificity. We
      compare our results with a recent mathematical analysis of the effect of
      crosstalk for exactly orthogonal mixing, which revealed that a second, even
      lower, threshold, exists below which successful learning is impossible unless
      weights happen to start close to the correct direction. Our simulations show that
      this also holds when the mixing is not exactly orthogonal. These results suggest
      that if the brain uses simple Hebbian learning, it must operate with
      extraordinarily accurate synaptic plasticity to ensure powerful high-dimensional
      learning. Synaptic crowding would preclude this when inputs are numerous, and we
      propose that the neocortex might be distinguished by special circuitry that
      promotes extreme specificity for high-dimensional nonlinear learning. 

PMID- 24862558
TI  - Bleeding risk assessment using point-of-care platelet function testing in
      patients undergoing coronary artery surgery: how to improve predictability.

PMID- 24862557
TI  - Adverse drug reactions in neonates and infants: a population-tailored approach is
      needed.
AB  - Drug therapy is a powerful tool to improve outcome, but there is an urgent need
      to improve pharmacotherapy in neonates through tailored prevention and management
      of adverse drug reactions (ADRs). At present, infants commonly receive off-label
      drugs, at dosages extrapolated from those in children or adults. Besides the lack
      of labelling, inappropriate formulations, (poly)pharmacy, immature organ function
      and multiple illnesses further raise the risk for ADRs in neonates and infants.
      Pharmacovigilance to improve the prevention and management of ADRs needs to be
      tailored to neonates and infants. We illustrate this using prevention strategies
      for drug prescription and administration errors (e.g. formulation, bedside
      manipulation, access), detection through laboratory signalling or clinical
      outlier data (e.g. reference laboratory values, overall high morbidity),
      assessment through algorithm scoring (e.g. Naranjo or population specific), as
      well as understanding of the developmental toxicology (e.g. covariates,
      developmental pharmacology) to avoid re-occurrence and for development of
      guidelines. Such tailored strategies need collaborative initiatives to combine
      the knowledge and expertise of different disciplines, but hold promise to become
      a very effective tool to improve pharmacotherapy and reduce ADRs in infants. 

PMID- 24862559
TI  - Oral administration of Polypodium leucotomos delays skin tumor development and
      increases epidermal p53 expression and the anti-oxidant status of UV-irradiated
      hairless mice.
AB  - Chronic exposure to ultraviolet radiation (UVR) induces skin tumors in hairless
      mice. Daily oral administration of a Polypodium leucotomos (PL) extract
      significantly delayed tumor development in PL-treated versus non-PL-treated mice.
      UVR and/or PL treatment modified several oxidative stress markers. In all
      irradiated mice, erythrocytic glutathione S-transferase (GST) activity and
      glutathione disulphide (GSSG) content increased and in all PL-treated mice GSSG
      content decreased, specially in non-irradiated animals, and total plasma anti
      oxidant capacity (ORAC) increased. In dorsolateral non-tumoral skin of all
      irradiated mice, glutathione reductase (GR) and glutathione peroxidase (GPx)
      activities increased and GSSG decreased in non-irradiated PL-treated animals. UVR
      induced a steep increase of p53 expression in epidermal cells. In non-tumoral
      skin, this increase was significantly higher in PL-treated animals than in non
      treated mice and can contribute in delaying tumor development, either by
      repairing the damaged DNA or by increasing apoptosis. These results reinforce the
      usefulness of PL as systemic photoprotective agent, especially in patients highly
      sensitive to UVR.

PMID- 24862560
TI  - Serotonin transporter gene methylation is associated with hippocampal gray matter
      volume.
AB  - BACKGROUND: The serotonin transporter (5-HTT) and the 5-HTTLPR/rs25531
      polymorphisms in its gene (SLC6A4) have been associated with depression,
      increased stress-response, and brain structural alterations such as reduced
      hippocampal volumes. Recently, epigenetic processes including SLC6A4 promoter
      methylation were shown to be affected by stress, trauma, or maltreatment and are
      regarded to be involved in the etiology of affective disorders. However,
      neurobiological correlates of SLC6A4 promoter methylation have never been studied
      or compared to genotype effects by means of human neuroimaging hitherto METHODS:
      Healthy subjects were recruited in two independent samples (N = 94, N = 95) to
      obtain structural gray matter images processed by voxel-based morphometry (VBM8),
      focusing on hippocampal, amygdala, and anterior cingulate gyrus gray matter
      structure. SLC6A4 promoter methylation within an AluJb element and 5
      HTTLPR/rs25531 genotypes were analyzed in view of a possible impact on local gray
      matter volume RESULTS: Strong associations of AluJb methylation and hippocampal
      gray matter volumes emerged within each sample separately, which in the combined
      sample withstood most conservative alpha-corrections for the entire brain. The
      amygdala, insula, and caudate nucleus showed similar associations. The 5
      HTTLPR/rs25531 showed no main effect on gray matter, and the effect of
      methylation rates on hippocampal structure was comparable among the genotype
      groups CONCLUSIONS: Methylation within the AluJb appears to have strong effects
      on hippocampal gray matter volumes, indicating that epigenetic processes can
      alter brain structures crucially involved in stress-related disorders. Different
      ways of regulating SLC6A4 expression might involve exonization or transcription
      factor binding as potentially underlying mechanisms, which, however, is
      speculative and warrants further investigation.

PMID- 24862561
TI  - Studying hemispheric lateralization during a Stroop task through near-infrared
      spectroscopy-based connectivity.
AB  - ABSTRACT. Near-infrared spectroscopy (NIRS) is a developing and promising
      functional brain imaging technology. Developing data analysis methods to
      effectively extract meaningful information from collected data is the major
      bottleneck in popularizing this technology. In this study, we measured
      hemodynamic activity of the prefrontal cortex (PFC) during a color-word matching
      Stroop task using NIRS. Hemispheric lateralization was examined by employing
      traditional activation and novel NIRS-based connectivity analyses simultaneously.
      Wavelet transform coherence was used to assess intrahemispheric functional
      connectivity. Spearman correlation analysis was used to examine the relationship
      between behavioral performance and activation/functional connectivity,
      respectively. In agreement with activation analysis, functional connectivity
      analysis revealed leftward lateralization for the Stroop effect and correlation
      with behavioral performance. However, functional connectivity was more sensitive
      than activation for identifying hemispheric lateralization. Granger causality was
      used to evaluate the effective connectivity between hemispheres. The results
      showed increased information flow from the left to the right hemispheres for the
      incongruent versus the neutral task, indicating a leading role of the left PFC.
      This study demonstrates that the NIRS-based connectivity can reveal the
      functional architecture of the brain more comprehensively than traditional
      activation, helping to better utilize the advantages of NIRS. 

PMID- 24862564
TI  - Routine prophylactic central neck dissection for low-risk papillary thyroid
      cancer is not cost-effective.
AB  - BACKGROUND: The role of routine prophylactic central neck dissection (CND) in
      papillary thyroid cancer (PTC) remains controversial. The aim of this study was
      to evaluate the cost utility of the addition of routine CND in patients with low
      risk PTC compared with total thyroidectomy (TT) alone. METHODS: A Markov model
      for low-risk PTC was constructed with a treatment algorithm based on the American
      Thyroid Association guidelines for well-differentiated thyroid carcinoma.
      Utilities and outcome probabilities were derived from published medical
      literature. US 2010 costs were examined from a society perspective using Medicare
      reimbursement rates and opportunity loss based on published US government data.
      Monte Carlo simulation and sensitivity analysis were used to examine the
      uncertainty of probability, cost and utility estimates. RESULTS: Initial TT alone
      is more cost-effective than TT with CND, resulting in a cost savings of US $5763
      per patient with slightly higher effectiveness per patient (0.03 QALY) for a cost
      savings of $285 per QALY. Sensitivity analysis shows that TT alone offers no
      advantage when radioactive iodine (RAI) becomes more detrimental to a patient's
      state of health, when the incidence of non-neck recurrence increases above 5% in
      patients undergoing TT alone or decreases below 3.9% in patients undergoing TT
      with CND or when the rate of permanent hypocalcaemia rises above 4%. CONCLUSIONS:
      TT with CND is not a cost-effective strategy in low-risk PTC. Initial TT alone is
      favourable because of the low complication rates and low recurrence rates
      associated with the initial surgery. Alternative strategies such as unilateral
      prophylactic neck dissection require additional study to assess their cost
      effectiveness.

PMID- 24862566
TI  - Invasive species challenge the global response to emerging diseases.
AB  - Forecasts of emerging zoonoses neglect the threat alien species pose in disease
      transmission to humans. A review of alien parasites, hosts, and vectors
      introduced to Europe highlights the wide range of potential public health risks,
      the need for better surveillance and risk assessment, and major policy gaps in
      global preparedness. 

PMID- 24862565
TI  - Human stem cells and surrogate tissues for basic and translational study of
      mental disorders.

PMID- 24862568
TI  - CD4-positive small T-cell lymphoma of the intestine presenting with severe bile
      acid malabsorption: a supportive symptom control approach.

PMID- 24862567
TI  - Methotrexate inhibits the viability of human melanoma cell lines and enhances
      Fas/Fas-ligand expression, apoptosis and response to interferon-alpha: rationale
      for its use in combination therapy.
AB  - Melanoma, a highly aggressive form of cancer, is notoriously resistant to
      available therapies. Methotrexate (MTX), an antifolate, competitively inhibits
      DNA synthesis and is effective for several types of cancer. In cutaneous T-cell
      lymphoma (CTCL), MTX increases Fas death receptor by decreasing Fas promoter
      methylation by blocking the synthesis of SAM, the principal methyl donor for
      DNMTs, resulting in enhanced Fas-mediated apoptosis. The objective of this study
      was to explore the effects of MTX in human melanoma. MTX variably inhibited the
      survival of melanoma cells and induced apoptosis as evident by annexin V
      positivity and senescence associated beta-galactosidase activity induction.
      Furthermore, MTX caused increased transcript and protein levels of extrinsic
      apoptotic pathway factors Fas and Fas-ligand, albeit at different levels in
      different cell lines. Our pyrosequencing studies showed that this increased
      expression of Fas was associated with Fas promoter demethylation. Overall, the
      ability of MTX to up-regulate Fas/FasL and enhance melanoma apoptosis through
      extrinsic as well as intrinsic pathways might make it a useful component of novel
      combination therapies designed to affect multiple melanoma targets
      simultaneously. In support of this concept, combination therapy with MTX and
      interferon-alpha (IFNalpha) induced significantly greater apoptosis in the
      aggressive A375 cell line than either agent alone. 

PMID- 24862569
TI  - Fetal thrombotic vasculopathy is associated with thromboembolic events and
      adverse perinatal outcome but not with neurologic complications: a retrospective
      cohort study of 54 cases with a 3-year follow-up of children.
AB  - OBJECTIVE: to test the hypothesis that placental fetal thrombotic vasculopathy
      (FTV) is associated with obstetric complications and predisposes the child to
      unfavorable outcomes. METHODS: 54 placentas with FTV lesions and 100 placentas
      without FTV lesions were collected over a 5-year period at the Croix-Rousse
      Pathology Department. Clinical findings including maternal, fetal, neonatal
      condition and pediatric outcome up to three years were collected for each case
      and control observation. The statistical analyses were assessed with Wald's chi
      square derived from conditional logistic regression modeling. RESULTS: FTV was
      associated with a significantly higher frequency of obstetric complications:
      (pregnancy-induced hypertension (OR 3.620, CI 1.563-8.385), preeclampsia (OR
      3.674, CI 1.500-8.998), emergency delivery procedures (OR 3.727, CI 1.477-9.403),
      cesarean sections (OR 2.684, CI 1.016-7.088)), poor fetal condition (intrauterine
      growth restriction (IUGR) (OR 5.440, CI 2.007-14.748), nonreassuring fetal heart
      tracing (OR 6.062, CI 2.280-16.115), difficulties in immediate ex utero
      adaptation (OR 3.416, CI 1.087-10.732)) and perinatal or early childhood demise
      (OR 3.043, CI 1.327-6.978). On pathological examination, FTV was associated with
      marginal cord insertion (OR 3.492, CI 1.350-9.035), cord stricture and
      hypercoiled cord (OR 3.936, CI 1.209-12.813). Thromboembolic events were
      significantly more frequent in cases with FTV (OR 2.154, CI 1.032-5.622).
      Neurological complications within the first 3 years of life were also more
      frequent in the FTV group compared to the control group, but this association was
      not statistically significant. CONCLUSIONS: FTV is associated with maternal
      complications, pathological findings in the placenta, especially gross cord
      abnormalities, IUGR, and poor perinatal or early childhood outcome. It may also
      predispose children to somatic thromboembolic events.

PMID- 24862570
TI  - Peter Cullen: nexins have it sorted.
AB  - Cullen studies protein sorting in the endosomal network.

PMID- 24862571
TI  - Organellophagy: eliminating cellular building blocks via selective autophagy.
AB  - Maintenance of organellar quality and quantity is critical for cellular
      homeostasis and adaptation to variable environments. Emerging evidence
      demonstrates that this kind of control is achieved by selective elimination of
      organelles via autophagy, termed organellophagy. Organellophagy consists of three
      key steps: induction, cargo tagging, and sequestration, which involve signaling
      pathways, organellar landmark molecules, and core autophagy-related proteins,
      respectively. In addition, posttranslational modifications such as
      phosphorylation and ubiquitination play important roles in recruiting and
      tailoring the autophagy machinery to each organelle. The basic principles
      underlying organellophagy are conserved from yeast to mammals, highlighting its
      biological relevance in eukaryotic cells. 

PMID- 24862572
TI  - Mammalian microtubule P-body dynamics are mediated by nesprin-1.
AB  - Nesprins are a multi-isomeric family of spectrin-repeat (SR) proteins,
      predominantly known as nuclear envelope scaffolds. However, isoforms that
      function beyond the nuclear envelope remain poorly examined. Here, we
      characterize p50(Nesp1), a 50-kD isoform that localizes to processing bodies
      (PBs), where it acts as a microtubule-associated protein capable of linking mRNP
      complexes to microtubules. Overexpression of dominant-negative p50(Nesp1) caused
      Rck/p54, but not GW182, displacement from microtubules, resulting in reduced PB
      movement and cross talk with stress granules (SGs). These cells disassembled
      canonical SGs induced by sodium arsenite, but not those induced by hydrogen
      peroxide, leading to cell death and revealing PB-microtubule attachment is
      required for hydrogen peroxide-induced SG anti-apoptotic functions. Furthermore,
      p50(Nesp1) was required for miRNA-mediated silencing and interacted with core
      miRISC silencers Ago2 and Rck/p54 in an RNA-dependent manner and with GW182 in a
      microtubule-dependent manner. These data identify p50(Nesp1) as a multi
      functional PB component and microtubule scaffold necessary for RNA granule
      dynamics and provides evidence for PB and SG micro-heterogeneity. 

PMID- 24862573
TI  - The Drosophila effector caspase Dcp-1 regulates mitochondrial dynamics and
      autophagic flux via SesB.
AB  - Increasing evidence reveals that a subset of proteins participates in both the
      autophagy and apoptosis pathways, and this intersection is important in normal
      physiological contexts and in pathological settings. In this paper, we show that
      the Drosophila effector caspase, Drosophila caspase 1 (Dcp-1), localizes within
      mitochondria and regulates mitochondrial morphology and autophagic flux. Loss of
      Dcp-1 led to mitochondrial elongation, increased levels of the mitochondrial
      adenine nucleotide translocase stress-sensitive B (SesB), increased adenosine
      triphosphate (ATP), and a reduction in autophagic flux. Moreover, we find that
      SesB suppresses autophagic flux during midoogenesis, identifying a novel negative
      regulator of autophagy. Reduced SesB activity or depletion of ATP by oligomycin A
      could rescue the autophagic defect in Dcp-1 loss-of-function flies, demonstrating
      that Dcp-1 promotes autophagy by negatively regulating SesB and ATP levels.
      Furthermore, we find that pro-Dcp-1 interacts with SesB in a nonproteolytic
      manner to regulate its stability. These data reveal a new mitochondrial
      associated molecular link between nonapoptotic caspase function and autophagy
      regulation in vivo. 

PMID- 24862574
TI  - CENP-I and Aurora B act as a molecular switch that ties RZZ/Mad1 recruitment to
      kinetochore attachment status.
AB  - The RZZ (Rod, ZW10, and Zwilch) complex and Mad1 proteins tightly associate with
      kinetochores to generate the spindle checkpoint signal, but they are released
      when a kinetochore forms mature microtubule attachments. Here we demonstrate that
      the centromere protein CENP-I is required to generate a stable association of RZZ
      and Mad1 with kinetochores. CENP-I also inhibits their removal by dynein
      stripping. This regulation of Mad1 and RZZ dissociation functions independently
      of Aurora B, which regulates their association. We show that the microtubule
      status of each kinetochore independently dictates the recruitment of Aurora B
      kinase, kinase activity on a kinetochore substrate, and loading of spindle
      checkpoint proteins. This dynamic regulation of Mad1 association by Aurora B is
      only uncovered when CENP-I is depleted, consistent with our finding that CENP-I
      inhibits the dissociation of Mad1. We conclude that the dual activities of Aurora
      B and CENP-I generate a molecular switch that maintains a robust spindle
      checkpoint signal at prometaphase kinetochores until they attain mature
      attachments to microtubules. 

PMID- 24862575
TI  - A TOGL domain specifically targets yeast CLASP to kinetochores to stabilize
      kinetochore microtubules.
AB  - Cytoplasmic linker-associated proteins (CLASPs) are proposed to function in cell
      division based on their ability to bind tubulin via arrayed tumor overexpressed
      gene (TOG)-like (TOGL) domains. Structure predictions suggest that CLASPs have at
      least two TOGL domains. We show that only TOGL2 of Saccharomyces cerevisiae CLASP
      Stu1 binds to tubulin and is required for polymerization of spindle microtubules
      (MTs) in vivo. In contrast, TOGL1 recruits Stu1 to kinetochores (KTs), where it
      is essential for the stability and tension-dependent regulation of KT MTs. Stu1
      is also recruited to spindle MTs by different mechanisms depending on the mitotic
      phase: in metaphase, Stu1 binds directly to the MT lattice, whereas in anaphase,
      it is localized indirectly to the spindle midzone. In both phases, the activity
      of TOGL2 is essential for interpolar MT stability, whereas TOGL1 is not involved.
      Thus, the two TOGL domains of yeast CLASP have different activities and execute
      distinct mitotic functions. 

PMID- 24862577
TI  - Morphology of the first zoeal stages of five species of the portunid genus
      Callinectes (Decapoda, Brachyura) hatched at the laboratory.
AB  - The genus Callinectes Stimpson, 1860 currently consists of 16 species, six of
      which are reported in Brazilian coast. In the present study, the first zoeal
      stages of Callinectes bocourti, C. danae, C. exasperatus, C. ornatus and C.
      sapidus from Brazil were obtained from ovigerous females. The morphological and
      meristic characters of all these larval stages are described and illustrated.
      Those of C. bocourti, C. danae and C. sapidus are redescribed and compared with
      the previous descriptions, and differences are listed. Larval characters of these
      species were examined for interspecific differences, as well as larval features
      to distinguish the genus Callinectes within Portunidae. In addition, other
      portunid genera and species with a known first zoeal stage are compared, with
      special attention to those species present in the same geographical area. Our
      findings concord with some previous molecular studies, and we discuss the
      complexity within the group.

PMID- 24862576
TI  - A new probe for super-resolution imaging of membranes elucidates trafficking
      pathways.
AB  - The molecular composition of the organelles involved in membrane recycling is
      difficult to establish as a result of the absence of suitable labeling tools. We
      introduce in this paper a novel probe, named membrane-binding fluorophore
      cysteine-lysine-palmitoyl group (mCLING), which labels the plasma membrane and is
      taken up during endocytosis. It remains attached to membranes after fixation and
      permeabilization and can therefore be used in combination with immunostaining and
      super-resolution microscopy. We applied mCLING to mammalian-cultured cells,
      yeast, bacteria, primary cultured neurons, Drosophila melanogaster larval
      neuromuscular junctions, and mammalian tissue. mCLING enabled us to study the
      molecular composition of different trafficking organelles. We used it to address
      several questions related to synaptic vesicle recycling in the auditory inner
      hair cells from the organ of Corti and to investigate molecular differences
      between synaptic vesicles that recycle actively or spontaneously in cultured
      neurons. We conclude that mCLING enables the investigation of trafficking
      membranes in a broad range of preparations. 

PMID- 24862578
TI  - Determination of soil-water sorption coefficients of volatile methylsiloxanes.
AB  - The sorption behaviors of 4 cyclic and linear volatile methyl siloxane (VMS)
      compounds between water and organic matter in 3 United Kingdom soils were studied
      by a batch equilibrium method using(13)C-enriched sorbates. Sorption and
      desorption kinetics and isotherms were determined for
      octamethylcyclotetrasiloxane (D4), decamethylcyclopentasiloxane (D5),
      octamethyltrisiloxane (L3), and decamethyltetrasiloxane (L4). Concentrations of
      [(13)C]-VMS in the soil and aqueous phases were measured directly by extraction
      and gas chromatography-mass spectrometry techniques. All VMS compounds were
      sorbed rapidly, reaching constant distributions in all soils by 24 h. Desorption
      kinetics were very rapid, with reattainment of equilibrium within 1 h. In the
      main, linear isotherms were observed for aqueous concentrations at or below 4% of
      the solubility limits. The average sorption organic carbon partition coefficient
      (logK(OC)) values across soils were 4.23 for D4, 5.17 for D5, 4.32 for L3, and
      5.13 for L4, with standard deviations of 0.09 to 0.34. Desorption K(OC) values
      were systematically greater by 0.1 log units to 0.3 log units. The linear
      isotherms and low variation in K(OC) values across soils suggested partitioning
      dominated sorption of the VMS. Compared with traditional hydrophobic organic
      compounds, K(OC) values for the VMS compounds were significantly lower than
      expected on the basis of their octanol-water partition coefficients. A linear
      free energy relationship analysis showed that these differences could be
      rationalized quantitatively in terms of the inherent characteristics of the VMS
      compounds, combined with the differences in solvation properties of organic
      matter and octanol.

PMID- 24862579
TI  - Combatting infectious diseases; nanotechnology as a platform for rational vaccine
      design.
AB  - Currently, several successful vaccines are available. However, for pathogens with
      a highly variable genetic composition, and for which serum IgG antibodies are not
      a useful correlate of protection, effective vaccines are yet to be developed.
      This is due to a lack of both the understanding of the immunological pathways
      leading to long-term protection and the ability to translate the available
      knowledge into a suitable vaccine formulation. Regarding the latter,
      nanoparticles can be an attractive platform for vaccine development, as they
      offer multiple options for improving safety and efficacy. For example, side
      effects might be decreased upon encapsulation of the adjuvant and the concomitant
      delivery of antigen and adjuvant is a very promising tool for increasing
      efficacy. In addition to the many promises, the use of nanoparticles as vaccine
      carriers should be implemented with caution: the more sophisticated a particle,
      the more parameters need to be controlled during production and storage. 

PMID- 24862580
TI  - Chromatic acclimation and population dynamics of green sulfur bacteria grown with
      spectrally tailored light.
AB  - Living organisms have to adjust to their surrounding in order to survive in
      stressful conditions. We study this mechanism in one of most primitive creatures 
      photosynthetic green sulfur bacteria. These bacteria absorb photons very
      efficiently using the chlorosome antenna complexes and perform photosynthesis in
      extreme low-light environments. How the chlorosomes in green sulfur bacteria are
      acclimated to the stressful light conditions, for instance, if the spectrum of
      light is not optimal for absorption, is unknown. Studying Chlorobaculum tepidum
      cultures with far-red to near-infrared light-emitting diodes, we found that these
      bacteria react to changes in energy flow by regulating the amount of light
      absorbing pigments and the size of the chlorosomes. Surprisingly, our results
      indicate that the bacteria can survive in near-infrared lights capturing low
      frequency photons by the intermediate units of the light-harvesting complex. The
      latter strategy may be used by the species recently found near hydrothermal vents
      in the Pacific Ocean. 

PMID- 24862583
TI  - Comment on Matsumura et al.: Changes in water content of intervertebral discs and
      paravertebral muscles before and after bed rest.

PMID- 24862582
TI  - Post-harvest control of gray mold in table grapes using volatile sulfur compounds
      from Allium sativum.
AB  - BACKGROUND: This study proposes the use of volatile sulfur compounds derived from
      garlic (Allium sativum) extracts applied via gas for the control of Botrytis
      cinerea, which causes post-harvest disease in table grapes. The effects of the
      volatile compounds emitted by garlic extract and sodium metabisulfite on conidia
      germination of B. cinerea were evaluated in vitro to assess their effectiveness
      at controlling grey mold on grapes stored at different temperatures. RESULTS:
      Diallyl disulfide, diallyl trisulfide and allicin were identified and quantified
      in a garlic extract using reversed-phase high-performance liquid chromatography.
      The volatile compounds emitted by the garlic extract in the form of allicin and
      diallyl trisulfide inhibited conidia germination of B. cinerea in vitro and
      significantly reduced the lesion diameters on stored grapes, which were similar
      to the effects of sodium metabisulfite, while the diallyl disulfide did not have
      any effect. The sulfhydryl groups of cysteine or reduced glutathione completely
      reversed the antifungal effect of these compounds. CONCLUSION: The antifungal
      activity that allicin and diallyl trisulfide, which are the volatile compounds
      emitted by a garlic extract, exerted on conidia germination of B. cinerea may be
      considered as an alternative for the control of gray mold in table grapes after
      harvest.

PMID- 24862581
TI  - Ambulatory cardiac rehabilitation improves pulsatile arterial hemodynamics: a
      pilot trial.
AB  - BACKGROUND: In patients with coronary heart disease, both arterial stiffness and
      wave reflections are increased and predict unfavorable cardiovascular events.
      Cardiac rehabilitation has the goal to reduce risk factors and slow the
      progression of the disease. The aim of this study was to prospectively determine
      the impact of an ambulatory cardiac rehabilitation program on pulsatile
      hemodynamics. METHODS: Male patients after coronary interventions, bypass
      surgery, or acute coronary syndromes underwent exercise and resistance training.
      Before and after the program, pulsatile hemodynamics was measured. Exercise
      capacity was assessed with an incremental cycle ergometer protocol. A detailed
      two-dimensional and Doppler echocardiogram was obtained for systolic and
      diastolic left ventricular function. RESULTS: A total of 27 men participated in
      the study. After the intervention (n = 24), carotid-femoral pulse wave velocity
      decreased significantly from 8.7 (standard deviation (SD): 1.7) to 7.9 (SD: 1.9)
      m/s (p = 0.019), and augmentation index normalized for a heart rate of 75/min
      decreased significantly from 20.4 (SD: 8.7) to 17.5 (SD: 8.1; p = 0.017).
      CONCLUSION: The results suggest that a structured ambulatory rehabilitation
      program may improve pulsatile hemodynamics in coronary artery disease (CAD)
      patients.

PMID- 24862584
TI  - De novo assembly and comparative analysis of the Ceratodon purpureus
      transcriptome.
AB  - The bryophytes are a morphologically and ecologically diverse group of plants
      that have recently emerged as major model systems for a variety of biological
      processes. In particular, the genome sequence of the moss, Physcomitrella patens,
      has significantly enhanced our understanding of the evolution of developmental
      processes in land plants. However, to fully explore the diversity within
      bryophytes, we need additional genomic resources. Here, we describe analyses of
      the transcriptomes of a male and a female isolate of the moss, Ceratodon
      purpureus, generated using the 454 FLX technology. Comparative analyses between
      C. purpureus and P. patens indicated that this strategy generated nearly complete
      coverage of the protonemal transcriptome. An analysis of the overlap in gene sets
      between C. purpureus and P. patens provides new insights into the evolution of
      gene family composition across the land plants. In spite of the overall
      transcriptomic similarity between the two species, Ka /Ks analysis of P. patens
      and C. purpureus suggests considerable physiological and developmental
      divergence. Additionally, while the codon usage was very similar between these
      two mosses, C. purpureus genes showed a slightly greater codon usage bias than P.
      patens genes potentially because of the contrasting mating system of the two
      species. Finally, we found evidence of a genome doubling ~65-76 MYA that likely
      coincided with the contemporaneous polyploidy event inferred for P. patens but
      postdates the divergence of P. patens and C. purpureus. The powerful laboratory
      tools now available for C. purpureus will enable the research community to fully
      exploit these genomic resources.

PMID- 24862586
TI  - Transient hyperckemia in the setting of neuromyelitis optica (NMO).
AB  - INTRODUCTION: Neuromyelitis optica (NMO) is characterized by inflammatory
      demyelinating lesions of the spinal cord and optic nerves from an autoimmune
      response against water channel aquaporin-4 (AQP4). We report 2 patients with
      transient hyperCKemia associated with NMO suggesting possible skeletal muscle
      damage. METHODS: Patient 1 was a 72-year-old man who presented with muscle
      soreness and elevated serum creatine kinase (CK) preceding an initial attack of
      NMO. Patient 2 was a 25-year-old woman with an established diagnosis of NMO who
      presented with diffuse myalgias, proximal upper extremity weakness, and
      hyperCKemia. Muscle biopsies were obtained for histopathologic evaluation,
      protein gel electrophoresis, immunofluorescence, and complement staining.
      RESULTS: In both patients the muscle showed only mild variation in fiber
      diameter. There were no inflammatory changes or muscle fiber necrosis, though
      there was reduced AQP4 expression and deposition of activated complement.
      CONCLUSIONS: Complement-mediated sarcolemmal injury may lead to hyperCKemia in
      NMO.

PMID- 24862585
TI  - Control over a stressor involves the posterior dorsal striatum and the
      act/outcome circuit.
AB  - Controllable/escapable tailshocks (ESs) do not produce the behavioral and
      neurochemical outcomes produced by equal yoked uncontrollable/inescapable
      tailshocks (ISs). The prelimbic cortex is known to play a key role in mediating
      the protective effects of control. The concepts of act/outcome learning and
      control seem similar, and act/outcome learning is mediated by a circuit involving
      the prelimbic cortex and posterior dorsomedial striatum (DMS). Thus, we tested
      the involvement of the DMS in the protective effect of ES, in rats. First, we
      examined Fos immunoreactivity in both the DMS and dorsolateral striatum (DLS)
      after ES and yoked IS. We then investigated the effect of blocking DMS or DLS N
      methyl-d-aspartate receptors with the specific antagonist D-(-)-2-amino-5
      phosphopentanoic acid (D-AP5) on the release of dorsal raphe nucleus serotonin (5
      HT) during ES, as well as on the level of anxiety produced by the ES experience
      24 h later. ES, but not yoked IS, produced a large increase of Fos activity in
      the DMS. Consistent with the Fos data, D-AP5 in the DMS, but not in the DLS,
      prevented the inhibition of dorsal raphe nucleus 5-HT release normally produced
      by ES. Furthermore, D-AP5 administered into the DMS before ES, but not into the
      DLS, increased anxiety 24 h later, leading to levels similar to those produced by
      IS. These results suggest that, as with appetitive act/outcome contingency
      learning, the protective effects of behavioral control over a stressor require
      the DMS. 

PMID- 24862587
TI  - Cognitive styles and clinical correlates of childhood abuse in bipolar disorder.
AB  - OBJECTIVES: In a relatively small number of previous studies, childhood abuse has
      been found to be associated with more severe symptom course, earlier onset,
      greater comorbidity, and greater suicidality in those diagnosed with bipolar
      disorder. There have been no prior reports looking for any association between
      childhood abuse and cognitive style. This study aimed to examine the relationship
      between cognitive factors, such as response styles to depressed mood and
      dysfunctional attitudes, clinical features, and childhood physical and sexual
      abuse in this population. METHODS: A total of 157 adult participants diagnosed
      with DSM-IV bipolar disorder I or II were assessed on clinical features of this
      condition and measures of childhood sexual and physical abuse. Participants also
      completed self-report questionnaires covering areas such as symptom measures of
      depression, anxiety and stress, dysfunctional attitudes, and response styles to
      depressed mood. RESULTS: Seventy-four participants (37%) reported having
      experienced either sexual or physical abuse. Those who reported physical or
      sexual abuse were significantly more likely to report self-harm or suicidal
      behaviors and showed higher stress scores. Specifically, those who reported
      sexual abuse were more likely to have simple phobias, to have attempted suicide,
      and to have had more hospitalizations for depression. After controlling for
      current mood severity, there were no significant differences on the self-report
      cognitive style measures for those who reported childhood sexual or physical
      abuse compared to those who did not report abuse. CONCLUSIONS: Cognitive styles
      were not found to be associated with childhood sexual or physical abuse in
      participants with bipolar disorder. Stress may be important to target in
      psychological interventions, whilst special attention should also be paid to
      those with a history of sexual abuse given the greater likelihood of suicide
      attempt.

PMID- 24862589
TI  - Effect of protic ionic liquid and surfactant structure on partitioning of
      polyoxyethylene non-ionic surfactants.
AB  - The partitioning constants and Gibbs free energies of transfer of
      poly(oxyethylene) n-alkyl ethers between dodecane and the protic ionic liquids
      (ILs) ethylammonium nitrate (EAN) and propylammonium nitrate (PAN) are
      determined. EAN and PAN have a sponge-like nanostructure that consists of
      interpenetrating charged and apolar domains. This study reveals that the ILs
      solvate the hydrophobic and hydrophilic parts of the amphiphiles differently. The
      ethoxy groups are dissolved in the polar region of both ILs by means of hydrogen
      bonds. The environment is remarkably water-like and, as in water, the solubility
      of the ethoxy groups in EAN decreases on warming, which underscores the critical
      role of the IL hydrogen-bond network for solubility. In contrast, amphiphile
      alkyl chains are not preferentially solvated by the charged or uncharged regions
      of the ILs. Rather, they experience an average IL composition and, as a result,
      partitioning from dodecane into the IL increases as the cation alkyl chain is
      lengthened from ethyl to propyl, because the IL apolar volume fraction increases.
      Together, these results show that surfactant dissolution in ILs is related to
      structural compatibility between the head or tail group and the IL nanostructure.
      Thus, these partitioning studies reveal parameters for the effective molecular
      design of surfactants in ILs. 

PMID- 24862591
TI  - Salivary secretion: mechanism and neural regulation.
AB  - Maintenance of a film of saliva on oral surfaces is dependent upon nerve
      mediated, reflex salivary gland secretion. Afferent signalling arises from taste,
      olfaction and mastication and is modified by signalling from other centres in the
      central nervous system before efferent signals are delivered to salivary glands
      in autonomic nerves. Salivary fluid secretion is largely dependent upon
      cholinergic signalling from parasympathetic nerves whilst the protein content of
      saliva is additionally dependent upon signalling by neuropeptides and, in the
      major (parotid, submandibular and sublingual) salivary glands, by sympathetic
      nerves and the release of noradrenaline. There have been significant recent
      advances in our understanding of the membrane transport proteins involved in
      intracellular calcium signalling in salivary acinar cells in response to nerve
      stimulation and of the ion transport proteins responsible for acinar cell
      secretion of saliva. Salivary glands retain an ability to regenerate following
      extreme atrophy, and autonomic nerves have an important role in both gland
      development and maintenance of long-term normal function. Continued advances in
      the understanding of the nerve-mediated regulation of salivary glands should help
      in the development of strategies for preventing chronic oral dryness resulting
      from drugs or atrophic disease associated with inflammation and irradiation.

PMID- 24862588
TI  - Hormesis results in trade-offs with immunity.
AB  - Many have argued that we may be able to extend life and improve human health
      through hormesis, the beneficial effects of low-level toxins and other stressors.
      But, studies of hormesis in model systems have not yet established whether stress
      induced benefits are cost free, artifacts of inbreeding, or come with deleterious
      side effects. Here, we provide evidence that hormesis results in trade-offs with
      immunity. We find that a single topical dose of dead spores of the
      entomopathogenic fungus, Metarhizium robertsii, increases the longevity of the
      fruit fly, Drosophila melanogaster, without significant decreases in fecundity.
      We find that hormetic benefits of pathogen challenge are greater in lines that
      lack key components of antifungal immunity (Dif and Turandot M). And, in outbred
      fly lines, we find that topical pathogen challenge enhances both survival and
      fecundity, but reduces ability to fight off live infections. The results provide
      evidence that hormesis is manifested by stress-induced trade-offs with immunity,
      not cost-free benefits or artifacts of inbreeding. Our findings illuminate
      mechanisms underlying pathogen-induced life-history trade-offs, and indicate that
      reduced immune function may be an ironic side effect of the "elixirs of life." 

PMID- 24862592
TI  - Salivary pellicles.
AB  - The salivary pellicle is a thin acellular organic film that forms on any type of
      surface upon exposure to saliva. The role of the pellicle is manifold, and it
      plays an important role in the maintenance of oral health. Its functions include
      not only substratum protection and lubrication, but also remineralization and
      hydration. It also functions as a diffusion barrier and possesses buffering
      ability. Not only the function, but also the formation, composition and stability
      of the pellicle are known to be highly influenced by the physicochemical
      properties of both substrata and ambient media. In this chapter, we discuss these
      aspects of salivary pellicles, an area where research has boomed in the past
      years partly because of the application of experimental techniques often reserved
      for more traditional surface science studies.

PMID- 24862590
TI  - Anatomy, biogenesis and regeneration of salivary glands.
AB  - An overview of the anatomy and biogenesis of salivary glands is important in
      order to understand the physiology, functions and disorders associated with
      saliva. A major disorder of salivary glands is salivary hypofunction and
      resulting xerostomia, or dry mouth, which affects hundreds of thousands of
      patients each year who suffer from salivary gland diseases or undergo head and
      neck cancer treatment. There is currently no curative therapy for these patients.
      To improve these patients' quality of life, new therapies are being developed
      based on findings in salivary gland cell and developmental biology. Here we
      discuss the anatomy and biogenesis of the major human salivary glands and the
      rodent submandibular gland, which has been used extensively as a research model.
      We also include a review of recent research on the identification and function of
      stem cells in salivary glands, and the emerging field of research suggesting that
      nerves play an instructive role during development and may be essential for adult
      gland repair and regeneration. Understanding the molecular mechanisms involved in
      gland biogenesis provides a template for regenerating, repairing or reengineering
      diseased or damaged adult human salivary glands. We provide an overview of 3
      general approaches currently being developed to regenerate damaged salivary
      tissue, including gene therapy, stem cell-based therapy and tissue engineering.
      In the future, it may be that a combination of all three will be used to repair,
      regenerate and reengineer functional salivary glands in patients to increase the
      secretion of their saliva, the focus of this monograph.

PMID- 24862593
TI  - Antimicrobial defense systems in saliva.
AB  - The oral cavity is one of the most heavily colonized parts of our body. The warm,
      nutrient-rich and moist environment promotes the growth of a diverse microflora.
      One of the factors responsible for the ecological equilibrium in the mouth is
      saliva, which in several ways affects the colonization and growth of bacteria. In
      this paper, we discuss the various mechanisms by which the composition of the
      oral microflora is modulated by saliva. Saliva covers the oral hard and soft
      tissues with a conditioning film which governs the initial attachment of
      microorganisms, a crucial step in the setup of the oral microflora. It
      furthermore contains proteins which in the soluble phase bind to bacteria,
      blocking their adherence to surfaces. When the supply of nutrients is diminished,
      bacteria use salivary glycoproteins, especially high-molecular-weight mucins, as
      a source of complex carbohydrates, requiring a consortium of microorganisms for
      breakdown. In this way saliva promotes the complexity of the oral microflora,
      which in itself protects against overgrowth by few pathogenic species. Finally,
      saliva harbors a large panel of antimicrobial proteins which directly and
      indirectly inhibit uncontrolled outgrowth of bacteria. These include lactoferrin,
      lactoperoxidase, lysozyme and antimicrobial peptides. Under pathological
      conditions serum leakage occurs, and saliva mobilizes the humoral and cellular
      defense mechanisms in the blood. In sum, saliva favors the establishment of a
      highly diverse microflora, rather than a semisterile environment.

PMID- 24862594
TI  - Saliva and wound healing.
AB  - Oral wounds heal faster and with less scar formation than skin wounds. One of the
      key factors involved is saliva, which promotes wound healing in several ways.
      Saliva creates a humid environment, thus improving the survival and functioning
      of inflammatory cells that are crucial for wound healing. In addition, saliva
      contains several proteins which play a role in the different stages of wound
      healing. Saliva contains substantial amounts of tissue factor, which dramatically
      accelerates blood clotting. Subsequently, epidermal growth factor in saliva
      promotes the proliferation of epithelial cells. Secretory leucocyte protease
      inhibitor inhibits the tissue-degrading activity of enzymes like elastase and
      trypsin. Absence of this protease inhibitor delays oral wound healing. Salivary
      histatins in vitro promote wound closure by enhancing cell spreading and cell
      migration, but do not stimulate cell proliferation. A synthetic cyclic variant of
      histatin exhibits a 1,000-fold higher activity than linear histatin, which makes
      this cyclic variant a promising agent for the development of a new wound healing
      medication. Conclusively, recognition of the many roles salivary proteins play in
      wound healing makes saliva a promising source for the development of new drugs
      involved in tissue regeneration.

PMID- 24862595
TI  - Role of saliva in oral food perception.
AB  - Saliva is the first fluid that comes into contact with food during oral
      processing. Because saliva is the medium that bathes the taste receptors, is the
      fluid through which taste and aroma compounds are released into the oral cavity
      and is mixed continuously with food during bolus formation, it is an essential
      actor in oral chemosensory perception. The complexity of saliva composition, with
      compounds originating from different salivary glands, from gingival crevicular
      fluid, from micro-organisms and from food debris, together with its variable
      nature increases the possibilities for interactions with food compounds and for
      different roles in perception. These factors are increasingly being taken into
      account in current research on food perception. The aim of this paper is to
      review the principal roles of saliva in oral perception, with particular focus on
      chemosensory perception. These include the protection of taste buds, the effects
      of flow rates, salivary hormones, electrolytes and organic compounds, and finally
      the impact of perception on salivary secretions.

PMID- 24862596
TI  - Lubrication.
AB  - Saliva is capable of decreasing friction force by at least 2 orders of magnitude
      when in between hydrophobic surfaces. This ability to lubricate is key to oral
      health, food processing and taste perception. In this paper different mechanisms
      of saliva lubrication are reviewed, and their interconnection is demonstrated
      using a simple physical framework. The current understanding of the roles of the
      molecular structure and physicochemical properties of major salivary proteins and
      protein complexes on lubrication is summarised and critically evaluated.

PMID- 24862597
TI  - Saliva diagnostics: utilizing oral fluids to determine health status.
AB  - Imagine a time where your health status could be available to you without the
      pain, discomfort and inconvenience of a physical examination. Distant vision of
      an inconceivable future or impending reality with potentially immeasurable
      impact? Recent advancements in the field of molecular diagnostics indicate this
      is not only possible, but closer than we think. Novel discoveries and substantial
      advancements have revealed that saliva may contain real-time information
      describing our overall physiological condition. Researchers are now reporting
      that, like blood and tissue biopsies, oral fluids could be a source of
      biochemical data capable of detecting certain diseases. What is even more
      intriguing is that this phenomenon not only applies to local disorders like oral
      cancer and Sjogren's syndrome, but distant pathologies like autoimmune,
      cardiovascular and metabolic diseases as well as viral/bacterial infections and
      even some cancers. These revelations have provided a foundation for the
      burgeoning field of salivary diagnostics and hence spurred the onset of
      investigations poised at deciphering the salivary milieu. This paper overviews
      salivary diagnostics from biomarker development to the multitude of techniques
      utilized in identifying saliva-based molecular indicators of disease. In doing
      so, we present oral fluids as an easily accessible noninvasive alternative to
      traditional diagnostic avenues and not just an essential component of the
      digestive process. Determining saliva as a credible means of evaluating health
      status represents a considerable leap forward in health care, one that could lead
      to enormous translational advantages and significant clinical opportunities.

PMID- 24862598
TI  - The use of saliva markers in psychobiology: mechanisms and methods.
AB  - In the social sciences, the use of saliva parameters has greatly expanded in
      recent years from the measurement of steroid hormones, like cortisol, and now
      includes a wide range of biochemical parameters. These salivary constituents can
      be broadly classified into two groups: (1) constituents that enter saliva from
      plasma (e.g. hormones, inflammatory markers, drug chemicals) and (2) constituents
      that are produced locally by the saliva glands (e.g. alpha-amylase, secretory
      IgA). Reliable measurement of blood-borne constituents assumes a constant
      saliva/plasma ratio (SPR), which implies that the concentration in saliva
      truthfully follows intra- and interindividual variations in plasma. The first
      part of this review discusses the main determinants of the SPR: the mechanism by
      which plasma constituents enter saliva (i.e. passive diffusion, active transport,
      ultrafiltration, leakage) and associated physiochemical factors. The second part
      of this review provides an overview of central and peripheral neural mechanisms
      that regulate saliva gland function and the release of glandular proteins. This
      section provides a neurobiological underpinning for a section, which addresses
      methodological implications for the assessment of glandular secretions. Salivary
      psychophysiology is a fast-growing field and the time seems ripe for more
      rigorous methodological studies that may help this discipline to reach its full
      potential.

PMID- 24862599
TI  - Xerostomia.
AB  - Xerostomia is the subjective feeling of oral dryness. The major causes are
      Sjogren's syndrome (SS), medication and radiotherapy to the head and neck. SS is
      a chronic systemic autoimmune disease characterized by infiltration of the
      exocrine glands, the salivary and lacrimal ones in particular. The pathogenesis
      involves systemic B cell hyperactivity and T cell lymphocytes targeting glandular
      epithelial cells. About 7.5% of patients with SS develop malignant B cell
      lymphoma, mostly mucosa-associated tissue lymphomas. Certain classes of drugs can
      induce hyposalivation and/or xerostomia by, e.g., targeting neurotransmitters and
      receptors. As a result, amongst others the production of fluid and electrolytes
      in salivary glands can be reduced and the salivary composition can change. During
      head and neck radiotherapy, the administration of high doses to the major
      salivary glands, which are located in the periphery of the head, leads to
      progressive loss of glandular function and a diminished salivary output.
      Reduction of the dose and the volume of irradiated salivary glands by advanced
      radiotherapy techniques can be highly beneficial for patients.

PMID- 24862600
TI  - Drooling.
AB  - The uncontrolled and continuous release of saliva from the mouth is known as
      drooling. While accepted as normal in young children up to 2 years of age,
      drooling in older children and adolescents is secondary to altered orofacial
      neuromuscular control during development, and in the elderly it is a consequence
      of neurodegenerative disease. The underlying cause is patient inability to seal
      the lips, excess salivation and the inability to adequately swallow saliva. The
      estimated mean prevalence of drooling in such elderly patients is 37%. Drooling
      can give rise to irritation and excoriation of the skin around the mouth or chin,
      favors infections and gives rise to speech or eating disorders. Observational
      methods based on collection of the leaked saliva or documentation of the affected
      skin zones can be used to measure drooling. The management of such patients
      requires a multidisciplinary approach and comprises myofunctional therapy,
      behavioral change techniques, the administration of antisialagogues, botulinum
      toxin, or the use of certain surgical techniques designed to reduce salivary
      secretion or to deviate it towards posterior areas of the oral cavity.

PMID- 24862601
TI  - Salivary gland diseases: infections, sialolithiasis and mucoceles.
AB  - The three most frequently diagnosed salivary gland diseases are salivary gland
      infections, sialolithiasis and mucoceles. Salivary gland infections are usually
      of bacterial or viral etiology and can be divided into acute and chronic types.
      Occasionally they can result from obstruction of the salivary duct, an
      autoimmmune disease or cancer therapy. Infections can occur in all types of
      salivary glands and are observed at all ages. Sialolithiasis is characterized by
      the development of calcified structures in the salivary glands, especially in the
      submandibular gland. Sialoliths are generally attributed to retention of saliva
      and are usually accompanied by swelling and pain when a salivary stimulus is
      applied. Mucoceles can be differentiated into mucus extravasation phenomenon or
      mucus escape reaction, mucus retention cysts and ranulas. They result from
      extravasation of saliva into the surrounding soft tissues or from retention of
      saliva within the duct.

PMID- 24862603
TI  - Anterior thalamic lesions reduce spine density in both hippocampal CA1 and
      retrosplenial cortex, but enrichment rescues CA1 spines only.
AB  - Injury to the anterior thalamic nuclei (ATN) may affect both hippocampus and
      retrosplenial cortex thus explaining some parallels between diencephalic and
      medial temporal lobe amnesias. We found that standard-housed rats with ATN
      lesions, compared with standard-housed controls, showed reduced spine density in
      hippocampal CA1 neurons (basal dendrites, -11.2%; apical dendrites, -9.6%) and in
      retrospenial granular b cortex (Rgb) neurons (apical dendrites, -20.1%) together
      with spatial memory deficits on cross maze and radial-arm maze tasks. Additional
      rats with ATN lesions were also shown to display a severe deficit on spatial
      working memory in the cross-maze, but subsequent enriched housing ameliorated
      their performance on both this task and the radial-arm maze. These enriched rats
      with ATN lesions also showed recovery of both basal and apical CA1 spine density
      to levels comparable to that of the standard-housed controls, but no recovery of
      Rgb spine density. Inspection of spine types in the CA1 neurons showed that ATN
      lesions reduced the density of thin spines and mushroom spines, but not stubby
      spines; while enrichment promoted recovery of thin spines. Comparison with
      enriched rats that received pseudo-training, which provided comparable task
      related experience, but no explicit spatial memory training, suggested that basal
      CA1 spine density in particular was associated with spatial learning and memory
      performance. Distal pathology in terms of reduced integrity of hippocampal and
      retrosplenial microstructure provides clear support for the influence of the ATN
      lesions on the extended hippocampal system. The reversal by postoperative
      enrichment of this deficit in the hippocampus but not the retrosplenial cortex
      may indicate region-specific mechanisms of recovery after ATN injury.

PMID- 24862604
TI  - Cell proliferation in in vivo-like three-dimensional cell culture is regulated by
      sequestration of ERK1/2 to lipid rafts.
AB  - OBJECTIVES: Regulatory mechanisms of cell proliferation have been extensively
      studied as they represent major challenges when dealing with pathologies such as
      fibrosis, tumourigenesis or tissue regeneration. Numerous in vitro studies still
      exploit conventional, two-dimensional cell cultures where cells are forced to
      adhere to unnaturally stiff and flat surfaces of culture dishes. In the living
      organism, however, each cell is in contact with components of the extracellular
      matrix and/or neighbouring cells, thus creating a complex three-dimensional (3D)
      tissue structure. The current paper describes a native 3D culture of cells, based
      on the GD25beta1 fibroblast cell line, and its use for investigating cell
      proliferation in in vivo-like conditions. MATERIALS AND METHODS: Four-day post
      confluent culture of GD25beta1 fibroblasts resulted in formation of a 3D system
      of cells embedded in naturally synthesized extracellular matrix. Morphological
      characterization of the culture was performed by histochemistry,
      immunohistochemistry and immunofluorescence. Viability/proliferation was assayed
      by MTT testing, FACS analysis and Western blotting for determination of
      expression levels and activation status of the relevant signalling molecules.
      RESULTS: GD25b1 fibroblasts, grown as 3D culture, gave rise to tissue-like
      structures characterized by low level of apoptosis, low senescence and
      development of 3D matrix adhesions, typical of living tissues. Transition to
      three-dimensionality led to a switch from exponential to linear culture growth,
      accompanied by accumulation of activated ERK1/2 into caveolin-containing raft
      domains. Disruption of raft domains as well as reverse transition from 3D back to
      monolayer culture led to release of phosphorylated ERK1/2 from rafts, activation
      of cyclin D1 expression and increase in proliferation levels. CONCLUSIONS: These
      results imply that under in vivo-like conditions, cells might achieve reduction
      of their proliferation level by sequestering activated ERK1/2 to lipid rafts.

PMID- 24862605
TI  - Bilateral subhyaloid haemorrhage in a conscious patient: a new spectrum of ocular
      involvement by Plasmodium falciparum.
AB  - A 24-year-old woman presented with a history of high-grade fever with rigours
      since 3 days and bilateral sudden loss of vision since 6 h. She was conscious,
      oriented and her vitals were stable. She had a temperature of 101 degrees F,
      anaemia, thrombocytopaenia, normal white cell count and moderate splenomegaly. On
      testing visual activity, she could only perceive hand movements although her
      pupils were bilaterally equal, and normal in size and reaction. On indirect
      ophthalmoscopy, optic discs were normal bilaterally; however, fovea of both eyes
      was masked by subhyaloid haemorrhage. Peripheral smear showed gametocytes of
      Plasmodium falciparum. The patient was started on arteminsinin-combined therapy
      and advised to be in propped-up position to help resolution of the haemorrhage.
      The patient was afebrile in 4 days and follow-up fundus examination showed
      gradual resolution of the haemorrhage. After two months, the patient regained
      normal visual acuity in both eyes; however, it took nearly 3 months for complete
      resolution of the haemorrhage.

PMID- 24862606
TI  - Classical windsock deformity of ruptured sinus of Valsalva: an unusual appearance
      on transthoracic echocardiography.

PMID- 24862607
TI  - Vitamin C supplementation has no effect on American bullfrog's immune response.
AB  - American bullfrog (Lithobates catesbeianus) is the only species raised in
      Brazilian commercial frog farms, and the intensive culture of these animals has
      gained great popularity in Brazil over the past several years. Stress is one of
      the major obstacles in frog culture. To minimise this problem, the aim of the
      present study was to investigate the role of added vitamin C in the diet of
      American bullfrogs as an antistress factor through the assessment of plasma
      corticosterone, leucocyte levels and macrophage activation in animals raised in
      confinement. The experimental design was entirely randomised, with six treatments
      (supplementation of 0, 250, 500, 750, 1000 and 2000 mg of vitamin C/kg of feed)
      and four replications. The plasma corticosterone level, leucocyte level and
      macrophage activation were evaluated. It was concluded that vitamin C had no
      influence on the evaluated parameters due to the possible adaptation of the
      animals to life in captivity (domestication). The results of this research
      indicate that farmers should not increase the levels of vitamin C in commercial
      feeds because this would only enhance production costs.

PMID- 24862608
TI  - Vascular biomarkers in cardiovascular risk prediction: the central role of the
      cardiologist.

PMID- 24862609
TI  - Radiation dose and image noise evaluation in coronary computed tomography
      angiography (CCTA) using an iterative reconstruction algorithm.
AB  - INTRODUCTION: The purpose of this study was to evaluate radiation dose reduction
      in coronary computerised tomography angiography (CCTA), using a commercially
      available iterative reconstruction (IR) algorithm as well as the behaviour of the
      image noise. METHODS: A total cohort of 47 patients underwent CCTA examination on
      a 64-slice multi-detector CT. They were divided into four groups according to the
      time when the examination was performed (before or after the installation of
      iDose) and the acquisition protocol followed (prospective or retrospective
      electrocardiography-ECG gated). The images acquired with reduced dose settings
      were reconstructed using two levels (L4 and L6) of the iDose4 algorithm. Image
      noise was measured in all cases. RESULTS: In retrospective acquisition, images
      acquired with a 46% lower radiation dose and reconstructed with iDose4 L6
      provided noise comparable to that in the full-dose filtered back-projection
      images. For the prospective acquisition mode, a slight decrease (26%) in
      radiation dose resulted in noise improvement in low-dose images reconstructed
      with iDose4 L4 (16% noise removal) and L6 (30% noise removal). CONCLUSIONS: The
      fact that image quality is improved while radiation exposure is reduced indicates
      that there is room for a further reduction in exposure settings. Additionally,
      the combination of iDose4 with prospective acquisition is able to significantly
      reduce the radiation dose associated with CCTA at values of about 2 mSv and even
      lower.

PMID- 24862610
TI  - Effects of anthracyclines on aortic distensibility in patients with lymphomas: a
      prospective study.
AB  - INTRODUCTION: Anthracyclines have been widely used in the treatment of
      haematological malignancies. Their major adverse effect is cardiomyopathy, but
      their effect on vascular elasticity has not been completely elucidated. The aim
      of the present study was to investigate the effects of anthracyclines on aortic
      elastic properties in patients with lymphomas. METHODS: We studied 70 patients
      with lymphomas, 37 males (52.9%), age 44 +/- 19 years, who were free of any
      cardiorenal or metabolic comorbidity. Forty-five (64.2%) had a non-Hodgkin
      lymphoma and the remainder a Hodgkin lymphoma. All participants were evaluated
      with echocardiography, laboratory and clinical examinations to estimate cardiac
      function and aortic elasticity in the following study phases: before the
      administration of anthracyclines (i.e. baseline), after three months, and after
      the end of treatment. RESULTS: A progressive decrease in aortic distensibility
      was observed over the three phases of the study (2.48 +/- 0.2 vs. 2.41 +/- 0.18,
      vs. 2.36 +/- 0.23, 10(-6).dyn(-1).cm(2); p<0.016 for all comparisons). A
      statistically significant decrease in left ventricular ejection fraction was also
      observed between baseline and final follow up. Significant negative predictors of
      aortic distensibility at final follow up were baseline age, systolic blood
      pressure, left atrial diameter, and left ventricular ejection fraction.
      CONCLUSIONS: Anthracycline therapy decreases aortic distensibility in patients
      with lymphomas.

PMID- 24862611
TI  - A short-term cost-effectiveness analysis of hypertension treatment in Greece.
AB  - INTRODUCTION: Hypertension represents one of the major contributors to the
      disease burden and to healthcare expenditure internationally. The objective of
      this paper was to conduct a short term cost-effectiveness analysis of
      hypertension treatment vs. a hypothetical "no-treatment" strategy in Greece.
      METHODS: Health-resource use data and clinical outcomes for a cohort of 1453
      hypertensive patients in Greece who were prospectively followed for a 1-year
      period served as the primary data for the analysis. Based on these data, the
      incremental cost per mmHg lowering in the baseline blood pressure (BP) and the
      incremental cost per patient that achieved BP control after 1 year of treatment
      were estimated. Costs were calculated from a social security perspective and are
      reported in year 2011 values. RESULTS: The average cost per mmHg lowering of
      baseline BP for the whole study sample was 13.7 +/- 14.2, ranging from 20.3 +/-
      21.4 for Grade 1 hypertension patients to 9.9 +/- 4.4 for Grade 3. The average
      cost per patient that achieved control after 1 year of treatment was 603.1 +/-
      215, with a range from 496.1 +/- 186.6 to 868 +/- 258.2 for Grades 1 and 3
      baseline BP, respectively. The sensitivity analysis corroborated the results.
      CONCLUSIONS: The present study outcomes compare favorably to corresponding
      results from the international literature and indicate the clinico-economic value
      of hypertension treatment in Greece, especially to those that are severely ill.
      In light of the current financial situation, resource allocation based on
      evidence from economic evaluation can constitute a core input in the decision
      making process for health policy.

PMID- 24862612
TI  - Emergency endovascular management of pulmonary artery aneurysms and
      pseudoaneurysms for the treatment of massive haemoptysis.
AB  - INTRODUCTION: In this study we report the results of endovascular techniques for
      the management of pulmonary artery aneurysms (PAA) and pseudoaneurysms (PAPS).
      METHODS: Cases with massive haemoptysis due to PAA and/or PAPS that were managed
      by endovascular means were included in the study. Clinical history and procedure
      details were analysed. Primary endpoints were immediate technical success and re
      intervention rate; secondary endpoints were survival rate and relapse of
      bleeding. RESULTS: Among the 72 patients with massive haemoptysis who were
      treated in our department during an 8-year period, 6 patients with 6 lesions (2
      PAA, 4 PAPS) fulfilled the inclusion criteria and were included in the study. The
      mean age was 46.5 years; mean lesion diameter was 12.7 mm (range 4-22 mm);
      underlying pathologies were vasculitis (n=2), erosion by necrotic tumour (n=1),
      previous lung surgery (n=1) and infectious disease (n=2). Four lesions were
      treated with coils, 1 with coils and a bare stent, and 1 with a covered stent.
      The technical success was 100%. Mean follow-up was 20.4 months. The re
      intervention rate was 50%, but in only 16.6% was it related to the treated
      lesions. Survival rate was 66.6%. There were no major or minor complications.
      CONCLUSION: Endovascular management offers a safe and effective solution for the
      emergency treatment of massive haemoptysis due to PAA and PAPS. A variety of
      endovascular devices may be used, according to the size and the anatomical
      location of the lesion.

PMID- 24862613
TI  - Renal denervation for resistant hypertension: acute results and long-term follow
      up.
AB  - INTRODUCTION: Renal sympathetic hyperactivity is vital for the maintenance and
      progression of essential hypertension. Catheter-based renal denervation is an
      evolving concept with favourable results regarding the control of hypertension;
      however, clinical experience is still limited. METHODS: We enrolled 15 patients
      with resistant hypertension who underwent percutaneous, catheter-based
      radiofrequency treatment for renal artery denervation. Patients were followed up
      for 4 to 13 months. RESULTS: Baseline mean blood pressure was 169/96 mmHg (SD
      9/11), and patients were receiving a mean 3.9 +/- 0.8 antihypertensive
      medications. Blood pressure values were reduced to 136/79 mmHg (SD 10/7), and
      antihypertensive medications to 2.9 +/- 0.8 at 6.9 +/- 3.4 months after the
      procedure. All procedures were uneventful and technically easy. The only
      drawbacks of the procedure are pain that the patient may feel during energy
      delivery, and the inability to obtain a sustained impedance reduction that allows
      completion of radiofrequency current delivery at some sites in the renal artery.
      CONCLUSIONS: Renal denervation facilitates control of resistant hypertension with
      reduction of medication, and appears to be a safe and technically easy procedure
      to accomplish.

PMID- 24862614
TI  - Primary prevention of cardiovascular disease in Greece: Greek results of the
      EURIKA study.
AB  - INTRODUCTION: The EURIKA study was designed to describe the control of
      cardiovascular disease (CVD) risk factors in a real-world primary prevention
      setting in Europe, to estimate residual CVD risk, and to assess physicians'
      attitudes to and perceptions of risk factor management. The present manuscript
      reports the EURIKA results from Greece. METHODS: EURIKA was a multinational,
      cross-sectional study conducted in 12 European countries. Randomly selected
      physicians completed a questionnaire regarding their demographics and CVD
      prevention beliefs and practices. Consenting patients who were free of CVD, aged
      50 years, and with 1 CVD risk factor, were recruited. Risk factor definition and
      treatment goals were based on the 2007 European guidelines on CVD prevention.
      Global CVD risk was estimated using the SCORE equation. In addition, each patient
      provided a fasting blood sample for measurement of serum lipids, and HbA1c.
      RESULTS: Overall, 620 evaluable patients (male/female 46%/54%) were enrolled by
      63 physicians (13 hospital-based, 50 office-based) across Greece. Almost one
      third of the patients (27.3%) were classified as highrisk (SCORE5%). Blood
      pressure, dyslipidaemia and diabetes were controlled in 47.5%, 37.4% and 43.8% of
      the population who were treated for the respective risk factors, with more than
      one-fourth of the controlled patients remaining at high risk. The ESC 2007 and
      ESC/ESH 2007 guidelines were the most popular (44.4% and 38.1% respectively),
      while the ESC/ESH tool was most frequently reported to be used by physicians for
      global CVD risk calculation (42%), followed by SCORE (36%), and Framingham (36%).
      The major barriers to the use of guidelines and risk calculation tools were the
      plethora of guidelines and time constraints (87.5% and 69.2% respectively).
      CONCLUSIONS: Control of key CVD risk factors appears to be suboptimal in primary
      prevention patients in Greece, with a remarkable proportion of controlled
      patients remaining at high risk. Although guidelines and global risk calculation
      tools are reported to be adopted by the majority of physicians, the plethora of
      available guidelines and time constraints are the major barriers to their
      utilisation.

PMID- 24862615
TI  - Organization, structure and data of the Hellenic Heart Registry on Percutaneous
      Coronary Interventions: a step forward towards outcomes research.
AB  - INTRODUCTION: The Hellenic Heart Registry on Percutaneous Coronary Interventions
      (HHR-PCI) was a prospective, observational registry of patients with stable
      angina or acute coronary syndromes who underwent percutaneous coronary
      intervention (PCI) between January 2008 and October 2010. METHODS: HHR-PCI was a
      database that used a secure web-based interface for data entry by individual
      users. All PCI centers and operators were invited to participate. The
      participating PCI centers were geographically divided into three main regions:
      Athens Metro Area, Thessaloniki Metro Area, and Rest of Greece. Indications,
      demographics, procedural characteristics, and in-hospital outcomes (death,
      myocardial infarction, cerebrovascular accidents) were recorded. RESULTS:
      Eighteen (18) centers participated in the registry (2008-2010) in a systematic
      fashion, entering complete data for 3441 patients (males 83.1%, mean age 64.1
      years, 5521 lesions). PCI was elective in 47.1% of patients and was used to treat
      an acute coronary syndrome in 52.5%. There were 742 (21.6%) patients treated for
      ST-segment elevation myocardial infarction, with 225 (30.3%) receiving primary
      PCI (mean door-to-balloon time 140 minutes). The mean numbers of stents per
      lesion and per patient were 1.14 and 1.74, respectively, with drug eluting stents
      being used in 74.2% of coronary lesions. Periprocedural complications were
      observed in 105 patients (3.1%), while the incidence of in-hospital death,
      myocardial infarction, and cerebrovascular event were 0.5%, 1%, and 0.6%,
      respectively. CONCLUSIONS: HHR-PCI was the first web-based national PCI registry
      in Greece and has provided useful insights regarding the practice of
      interventional cardiology in this country. Efforts should be made to maintain and
      extend this type of PCI registry, with a view to improving quality and outcomes
      research in the field of interventional cardiology.

PMID- 24862616
TI  - The value of left ventricular global longitudinal strain assessed by three
      dimensional strain imaging in the early detection of anthracyclinemediated
      cardiotoxicity.
AB  - INTRODUCTION: Anthracyclines are important anticancer drugs, but their use is
      limited by acute and chronic cardiotoxicity. Current approaches to surveillance
      are often inadequate to detect myocardial disease. Strain imaging might detect
      earlier myocardial dysfunction. Speckle analysis of three-dimensional (3D)
      echocardiography improves information about left ventricular (LV) segmental and
      global deformation by avoiding the loss of speckles seen in monoplane
      bidimensional-strain analysis. We assessed whether early 3D-strain analysis could
      predict later anthracycline-induced cardiotoxicity. METHODS: Echocardiography,
      troponin T (TnT) and N-terminal pro-brain natriuretic peptide were used to
      evaluate 59 patients (age 51 +/- 10 years) before, and at 12 and 36 weeks after
      anthracycline treatment. LV global longitudinal strain (3DGLS), global radial
      strain (3DGRS) and global circumferential strain (3DGCS) were determined using 3D
      strain imaging before and after 12 weeks of chemotherapy. Percentage changes from
      baseline to 12 weeks after initiation of chemotherapy () were calculated for all
      parameters analysed. RESULTS: During the follow-up period, eight patients (13.5%)
      developed cardiotoxicity. At 12 weeks after the initiation of chemotherapy,
      isovolumic relaxation time, 3DGLS, 3DGCS and 3DGRS had deteriorated and troponin
      was elevated (all p<0.05), before any decrease in LV ejection fraction.
      Cumulative anthracycline dose at 12 weeks, LVEF, 3DGLS and TnT were predictors of
      the later development of cardiotoxicity on univariate logistic regression. By
      multiple logistic regression, 3DGLS emerged as the only independent predictor of
      later cardiotoxicity (Odds ratio 1.09, p=0.04). CONCLUSIONS: Anthracycline
      therapy induced early deterioration of 3DGLS, 3DGCS and 3DGRS. 3DGLS seems to be
      a good predictor of the future development of anthracycline-induced
      cardiotoxicity.

PMID- 24862617
TI  - Remote ischemic preconditioning for reduction of peri-procedural myocardial
      injury during percutaneous coronary intervention.

PMID- 24862618
TI  - Left subclavian artery cannot be the thief because there is no coronary flow to
      be stolen.

PMID- 24862620
TI  - Giant cardiac hydatid cyst with rare adhesions.
AB  - We present a 29-year-old woman who was admitted to the emergency department with
      shortness of breath. Using echocardiography, a giant multi-cystic mass was
      detected in the right ventricle, attached to the septal leaflet of the tricuspid
      valve and basal portion of the interventricular septum. Serologic tests (hydatid
      cyst antibody) confirmed Echinococcus infection. Lung computed tomography with
      intravenous contrast showed involvement of the pulmonary vasculature. The patient
      underwent cardiac surgery and the large cardiac cyst and the one in the right
      pulmonary artery branch were both removed. The tricuspid valve was also replaced
      by a bioprosthetic one. Albendazole was started preoperatively and was continued
      for six months after surgery. The patient recovered uneventfully and was followed
      up for one year. This is a report of a rare case of a very large cardiac hydatid
      cyst complicated by pulmonary embolism with attachments to both the tricuspid
      valve and interventricular septum. 

PMID- 24862621
TI  - Heart failure with preserved ejection fraction.

PMID- 24862619
TI  - Sinus of Valsalva fistula to right chambers: an infrequent pathology.

PMID- 24862622
TI  - Bioelectronics: the way to discover the world of arrhythmias?

PMID- 24862624
TI  - The Huntington's Disease Dysphagia Scale.
AB  - BACKGROUND: Little is known about the swallowing disturbances of patients with
      Huntington's disease; therefore, we developed the Huntington's Disease Dysphagia
      Scale. METHODS: The scale was developed in four stages: (1) item generation, (2)
      comprehension testing, (3) evaluation of reliability, (4) item reduction and
      validity testing. The questionnaire was presented twice to 50 Huntington's
      disease patients and their caregivers. The Kruskal-Wallis test was used to
      evaluate whether the severity of swallowing difficulties increased with advancing
      disease. Pearson's correlation coefficient was used to examine the construct
      validity with the Swallowing Disturbance Questionnaire. RESULTS: The final
      version contained 11 items with five response options and exhibited a Cronbach's
      alpha coefficient of 0.728. The severity of swallowing difficulties was
      significantly higher in more advanced Huntington's disease. The correlation with
      the Swallowing Disturbance Questionnaire was 0.734. CONCLUSION: We developed a
      valid and reliable 11-item scale to measure the severity of dysphagia in
      Huntington's disease.

PMID- 24862623
TI  - Nebulized hypertonic saline for bronchiolitis: a randomized clinical trial.
AB  - IMPORTANCE: Bronchiolitis is one of the most common and costly respiratory
      diseases in infants and young children. Previous studies have shown a potential
      benefit of nebulized hypertonic saline; however, its effect in the emergency
      department (ED) setting is unclear. OBJECTIVE: To compare the effect of nebulized
      3% hypertonic saline vs 0.9% normal saline on admission rate and length of stay
      in infants with bronchiolitis. DESIGN, SETTING, AND PARTICIPANTS: We conducted a
      double-blind, randomized clinical trial during 3 consecutive bronchiolitis
      seasons from March 1, 2008, through April 30, 2011. We recruited a convenience
      sample of patients younger than 24 months with a primary diagnosis of viral
      bronchiolitis presenting to the ED of 2 urban free-standing tertiary children's
      hospitals. We excluded patients who were premature (gestational age, <34 weeks)
      or who had chronic pulmonary disease, immune deficiency, cardiac disease, or
      previous episodes of wheezing or inhaled bronchodilator use. Of eligible patients
      who were approached, 161 (26.6%) declined to participate. INTERVENTIONS: Patients
      received 4 mL of 3% sodium chloride (hypertonic saline [HS group]) or 0.9% sodium
      chloride (normal saline [NS group]) inhaled as many as 3 times in the ED. Those
      admitted received the assigned medication every 8 hours until discharge. All
      treatment solutions were premedicated with albuterol sulfate. MAIN OUTCOMES AND
      MEASURES: Hospital admission rate, length of stay for admitted patients, and
      Respiratory Distress Assessment Instrument score. RESULTS: A total of 197
      patients were enrolled in the NS group and 211 in the HS group. Admission rate in
      the 3% HS group was 28.9% compared with 42.6% in the NS group (adjusted odds
      ratio from logistic regression, 0.49 [95% CI, 0.28-0.86]). Mean (SD) length of
      stay for hospitalized patients was 3.92 (5.24) days for the NS group and 3.16
      (2.11) days for the HS group (P = .24). The Respiratory Distress Assessment
      Instrument score decreased after treatment in both groups; however, we found no
      significant difference between groups (P = .35). CONCLUSIONS AND RELEVANCE:
      Hypertonic saline given to children with bronchiolitis in the ED decreases
      hospital admissions. We can detect no significant difference in Respiratory
      Distress Assessment Instrument score or length of stay between the HS and NS
      groups. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00619918.

PMID- 24862625
TI  - Thrombolytic effects in vivo of nattokinase in a carrageenan-induced rat model of
      thrombosis.
AB  - BACKGROUND/AIMS: Nattokinase is a serine protease produced by Bacillus subtilis
      during the fermentation of the soybean product natto. The fibrinolytic activity
      and thrombolytic effects of nattokinase have been observed in vitro, but the
      effect in vivo has still to be researched. The objective of this study was to
      demonstrate the activity of nattokinase in vivo. METHODS: To establish a rat
      model of thrombosis, kappa-carrageenan was injected subcutaneously into the toes
      of Sprague-Dawley (SD) rats. Histological examination confirmed thrombosis. The
      rats were then treated with varying doses of nattokinase and the resulting
      thrombolysis was histologically assessed. ELISA was used to determine the levels
      of the fibrin/fibrinogen degradation products (FDPs) and D-dimer, which are
      sensitive indices of fibrinolytic activity. Vermis kinase, a known thrombolytic
      agent, was used as a positive control. RESULTS: Biopsy results revealed partial
      thrombolysis in the tail vessels of the rats treated with nattokinase or vermis
      kinase. FDP and D-dimer levels were higher in rats treated with high-dose
      nattokinase than in those treated with saline. No difference in FDP or D-dimer
      levels was observed between rats treated with high-dose nattokinase and those
      treated with vermis kinase. CONCLUSIONS: Both the histological and physiological
      evidence from this study indicate that nattokinase exerts thrombolytic effects in
      vivo.

PMID- 24862626
TI  - Miniaturized dielectric barrier discharge carbon atomic emission spectrometry
      with online microwave-assisted oxidation for determination of total organic
      carbon.
AB  - A simple, rapid, and portable system consisted of a laboratory-built miniaturized
      dielectric barrier discharge atomic emission spectrometer and a microwave
      assisted persulfate oxidation reactor was developed for sensitive flow injection
      analysis or continuous monitoring of total organic carbon (TOC) in environmental
      water samples. The standard/sample solution together with persulfate was pumped
      to the reactor to convert organic compounds to CO2, which was separated from
      liquid phase and transported to the spectrometer for detection of the elemental
      specific carbon atomic emission at 193.0 nm. The experimental parameters were
      systematically investigated. A limit of detection of 0.01 mg L(-1) (as C) was
      obtained based on a 10 mL sample injection volume, and the precision was better
      than 6.5% (relative standard deviation, RSD) at 0.1 mg L(-1). The system was
      successfully applied for TOC analysis of real environmental water samples. The
      obtained TOC value of 30 test samples agreed well with those by the standard high
      temperature combustion coupled nondispersive infrared absorption method. Most
      importantly, the system showed good capability of in situ continuous monitoring
      of total organic carbon in environmental water. 

PMID- 24862627
TI  - Effects of posture on tactile localization by 4 years of age are modulated by
      sight of the hands: evidence for an early acquired external spatial frame of
      reference for touch.
AB  - Adults show a deficit in their ability to localize tactile stimuli to their hands
      when their arms are in the less familiar, crossed posture. It is thought that
      this 'crossed-hands deficit' arises due to a conflict between the anatomical and
      external spatial frames of reference within which touches can be encoded. The
      ability to localize a single tactile stimulus applied to one of the two hands
      across uncrossed-hands and crossed-hands postures was investigated in typically
      developing children (aged 4 to 6 years). The effect of posture was also compared
      across conditions in which children did, or did not, have visual information
      about current hand posture. All children, including the 4-year-olds, demonstrated
      the crossed-hands deficit when they did not have sight of hand posture,
      suggesting that touch is located in an external reference frame by this age. In
      this youngest age group, when visual information about current hand posture was
      available, tactile localization performance was impaired specifically when the
      children's hands were uncrossed. We propose that this may be due to an early
      difficulty with integrating visual representations of the hand within the body
      schema. 

PMID- 24862629
TI  - Winners of the 2013 JA Medals for excellence.

PMID- 24862628
TI  - Impact of metabolic syndrome on benign prostatic hyperplasia in elderly Chinese
      men.
AB  - OBJECTIVE: The aim of the present study was to evaluate the impact of metabolic
      syndrome (MetS) on benign prostatic hyperplasia (BPH) in elderly Chinese men.
      METHODS: A total of 401 elderly BPH patients were divided into the without or
      with MetS group to assess the associations of MetS and components of MetS with
      BPH. Urologic evaluation included prostate volume, International Prostate Symptom
      Score, serum prostate-specific antigen, duration of concomitant lower urinary
      tract symptoms (LUTS) and maximum flow rate. RESULTS: Body mass index (BMI),
      waist circumference, fasting glucose, glycosylated hemoglobin, triglyceride,
      fasting insulin (FINS), insulin resistance assessed by homeostasis model
      assessment (HOMA-IR) were greater and high-density lipoprotein cholesterol (HDL
      C) was lower in BPH patients with MetS than in those without MetS. The patients
      with MetS showed a significantly larger prostate volume (p = 0.000) and longer
      duration of LUTS (p = 0.006) than those without MetS. Prostate volume was
      positively correlated with BMI (p = 0.000), FINS (p = 0.001), HOMA-IR (p = 0.003)
      and inversely correlated with HDL-C (p = 0.000). Multiple linear regression
      analysis showed that prostate volume was significantly correlated with HOMA-IR (p
      = 0.015). CONCLUSIONS: Our results suggest that MetS, BMI, low HDL-C level,
      increased serum insulin and especially insulin resistance are considered risk
      factors for prostate enlargement in elderly Chinese men.

PMID- 24862630
TI  - Obstetric complications and eating disorders: a replication study.
AB  - OBJECTIVE: To provide data about the role of obstetric complications (OCs) in a
      large and well-characterized sample of patients with anorexia nervosa (AN) or
      bulimia nervosa (BN). METHOD: The new sample consists of 150 patients with AN and
      35 patients with BN, and 73 healthy women; statistical analyses were performed on
      the new sample alone and on the larger sample created by merging the new dataset
      with the previous one (264 AN, 108 BN, and 624 healthy women). All data about OCs
      were collected blind to diagnostic status. RESULTS: OC rates in the replication
      sample were similar to those of our previous studies. In the whole sample, the
      risk of developing AN was significantly associated with the occurrence and number
      of pregnancy, delivery, hypoxic, and dysmaturity complications. The risk of
      developing BN was significantly associated with dysmaturity complications. Signs
      of retarded fetal growth (being small and short for gestational age, short head
      circumference) significantly distinguished BN patients from both AN and healthy
      individuals. Significantly higher number of OCs were found in the binge
      eating/purging type of AN, in comparison with restricting AN patients.
      DISCUSSION: Our study provides further evidence of the role of OCs as putative
      risk factors for the development of eating disorders, showing different pathways
      between AN and BN.

PMID- 24862631
TI  - Solitary fibrous tumours in the extracranial head and neck region: correlation of
      CT and MR features with pathologic findings.
AB  - PURPOSE: Solitary fibrous tumours (SFTs) are rare, mesenchymal neoplasms. The
      purpose of this study was to analyse the radiological and clinicopathological
      features of SFTs in the extracranial head and neck region. MATERIALS AND METHODS:
      We retrospectively reviewed the clinical, computed tomography (CT), magnetic
      resonance imaging (MRI), and pathological features in 18 patients (12 men and 6
      women), aged 18-75 years, with histologically proven SFTs in the extracranial
      head and neck region. Fourteen patients underwent CT scanning and nine underwent
      MRI. The histological techniques included routine haematoxylin-eosin staining and
      immunohistochemical analysis. Clinical data were retrieved from the medical
      records. RESULTS: Most tumours presented as a slow-growing painless mass.
      Eighteen SFTs arose in the orbit, cheek, masticator space, the parapharyngeal
      space, infratemporal fossa, maxillary, submandibular space and the parotid gland,
      respectively. All 18 lesions were found as a solitary mass, ranging in size from
      1.2 to 6.8 cm (mean 3.57 cm). They mostly presented with an ovoid shape, with
      well-defined margin, and isodensity on plain CT, isointensity on T1-weighted
      imaging, mild hyperintensity on T2-weighted imaging and diffusion-weighted
      imaging, and marked heterogeneous enhancement on contrast-enhanced CT and MRI.
      The time-intensity curves (TICs) exhibited a rapidly enhancing and slow washout
      pattern on dynamic contrast-enhanced MRI and dual-phase CT. Imaging findings of
      the SFTs depended on the histopathological components. CONCLUSION: SFTs most
      commonly present with an asymptomatic mass in adults. A solitary, ovoid and well
      defined mass with strong enhancement after contrast agent injection is suggestive
      of this diagnosis. Rapidly enhancing and slow washout pattern TICs may be
      additional valuable features.

PMID- 24862632
TI  - Value of magnetic resonance imaging in brucellar spondylodiscitis.
AB  - PURPOSE: The aim of this retrospective study was to evaluate magnetic resonance
      (MR) imaging in patients with brucellar spondylodiscitis. MATERIALS AND METHODS:
      Sixty-three patients with spondylodiscitis were diagnosed based on positive
      clinical findings, >=1/160 titres of brucella agglutination tests and/or positive
      blood cultures. MR imaging was performed in all of the patients with
      spondylodiscitis. Signal changes and enhancement of vertebral bodies, involvement
      of paravertebral soft tissues and epidural spaces, nerve root and cord
      compression and abscess formation were assessed. RESULTS: Of 63 patients with
      spinal brucellosis, eight had thoracic, 35 had lumbar, ten had cervical
      vertebral, seven had both thoracic and lumbar, and three had both lumbar and
      sacral vertebral involvement. Thirteen patients had cord compression and six had
      root compression. Four patients had facet-joint involvement, and one had erector
      spinae muscle involvement. Twenty-four had intervertebral disc narrowing.
      Seventeen patients were in the acute stage, 32 in the subacute stage and 14 in
      the chronic stage. Vertebral bodies, vertebral end plates and intervertebral disc
      spaces were hypointense and hyperintense in the acute stage, whereas they were
      hypointense and heterogeneous in the subacute and chronic stages on T1- and T2
      weighted images, respectively. CONCLUSION: Brucella is still a public health
      problem in endemic areas. MR imaging is a highly sensitive and noninvasive
      imaging technique which should be first choice of imaging in the early diagnosis
      of spondylodiscitis.

PMID- 24862633
TI  - Health-related quality of life from a prospective randomised clinical trial of
      robot-assisted laparoscopic vs open radical cystectomy.
AB  - OBJECTIVE: To compare health-related quality-of-life (HRQoL) outcomes for robot
      assisted laparoscopic radical cystectomy (RARC) with those of traditional open
      radical cystectomy (ORC) in a prospective randomised fashion. PATIENTS AND
      METHODS: This was a prospective randomised clinical trial evaluating the HRQoL
      for ORC vs RARC in consecutive patients from July 2009 to June 2011. We
      administered the Functional Assessment of Cancer Therapy-Vanderbilt Cystectomy
      Index questionnaire, validated to assess HRQoL, preoperatively and then at 3, 6,
      9 and 12 months postoperatively. Scores for each domain and total scores were
      compared in terms of deviation from preoperative values for both the RARC and the
      ORC cohorts. Multivariate linear regression was used to assess the association
      between the type of radical cystectomy and HRQoL. RESULTS: At the time of the
      study, 47 patients had met the inclusion criteria, with 40 patients being
      randomised for analysis. The cohorts consisted of 20 patients undergoing ORC and
      20 undergoing RARC, who were balanced with respect to baseline demographic and
      clinical features. Univariate analysis showed a return to baseline scores at 3
      months postoperatively in all measured domains with no statistically significant
      difference among the various domains between the RARC and the ORC cohorts.
      Multivariate analysis showed no difference in HRQoL between the two approaches in
      any of the various domains, with the exception of a slightly higher physical well
      being score in the RARC group at 6 months. CONCLUSIONS: There were no significant
      differences in the HRQoL outcomes between ORC and RARC, with a return of quality
      of life scores to baseline scores 3 months after radical cystectomy in both
      cohorts.

PMID- 24862634
TI  - Age-dependent and differential effects of Smad7DeltaEx1 on neural progenitor cell
      proliferation and on neurogenesis.
AB  - We recently reported that young (3 to 4months old) mice lacking Exon 1 of the
      Smad7 gene (S7DeltaEx1 mice) show enhanced proliferation of neural stem and
      progenitor cells (NPCs) in the hippocampal dentate gyrus (DG) and in the
      subventricular zone (SVZ) of the lateral ventricles. It remained unclear,
      however, whether this phenotype would persist along aging, the latter typically
      being associated with a profound decrease in neurogenesis. Analysis of NPCs'
      proliferation based on the cell cycle marker PCNA in 12month-old S7DeltaEx1 mice
      revealed a reversal of the phenotype. Hence, in contrast to their younger
      counterparts, 12month-old S7DeltaEx1 mice had a reduced number of proliferating
      cells, compared to wildtype (WT) mice. At the same time, the survival of newly
      generated cells was enhanced in the aged transgenic animals. 12month-old
      S7DeltaEx1 mice further displayed a reduced level of neurogenesis based on the
      numbers of cells expressing doublecortin (DCX), a marker for newborn neurons. The
      reduced neurogenesis in aged S7DeltaEx1 mice was not due to a stem cell
      depletion, which might have occurred as a consequence of hyperproliferation in
      the young mice, since the number of Nestin and Sox2 positive cells was similar in
      WT and S7DeltaEx1 mice. Instead, Nestin positive cells in the DG as well as
      primary neurosphere cultures derived from 12month-old S7DeltaEx1 mice had a
      reduced capability to proliferate. However, after passaging, when released from
      their age- and niche-associated proliferative block, neurospheres from aged
      S7DeltaEx1 mice regained the hyperproliferative property. Further, pSmad2
      antibody staining intensity was elevated in the DG and SVZ of 12-month old
      transgenic compared to WT mice, indicating increased intracellular TGF-beta
      signaling in the aged S7DeltaEx1 mice. In summary, this points toward
      differential effects of S7DeltaEx1 on neurogenesis: (i) a hyperproliferation in
      young animals caused by a cell autonomous mechanism, and (ii) a TGF-beta
      dependent modulation of neurogenesis in aged S7DeltaEx1 animals that abrogates
      the cell-intrinsic hyperproliferative properties and results in reduced
      proliferation, increased stem cell quiescence, and enhanced survival of newly
      generated cells. 

PMID- 24862635
TI  - Association of CRP gene polymorphisms with serum CRP level and handgrip strength
      in community-dwelling elders in Taiwan: Taichung Community Health Study for
      Elders (TCHS-E).
AB  - Low handgrip strength is one component of frailty, characterized by loss of
      reserves, including energy, physical ability, cognition and health. This study
      rated the effect of five single-nucleotide polymorphisms (SNPs) in C-reactive
      protein (CRP) gene on the serum CRP level and handgrip strength in elderly
      Taiwanese. Five SNPs (rs2794520, rs1205, rs1130864, rs1800947, and rs3093059) of
      CRP gene were utilized to genotype 472 unrelated elderly subjects (mean age
      73.8years). Handgrip strength was measured by handgrip dynamometer (TTM
      Dynamometer, Tsutsumi, Tokyo). Our study demonstrated that minor alleles of
      rs2794520 and rs1205 were C, whereas they were T in most ethnic groups. There
      exist significant associations of three CRP polymorphisms (rs2794520, rs1205 and
      rs3093059) with serum CRP level and handgrip strength. All three had simultaneous
      influence on raising CRP levels and reducing handgrip strength. Genotype and sex
      interactions emerged for rs2794520 and rs1205 in relation to CRP levels (p<0.05).
      In addition, haplotype C-C-C-C-C was associated with higher levels of CRP
      (exp(beta)=1.45; p<0.001) and lower handgrip strength (beta=-1.00kg, p<0.05). We
      conclude that SNPs rs2794520, rs1205, and rs3093059 of CRP gene, as well as
      haplotype C-C-C-C-C may be important biomarkers for susceptibility to low
      handgrip strength and high serum CRP level in elders; further studies are
      required. 

PMID- 24862636
TI  - Clinical features of hyperadrenergic postural tachycardia syndrome in children.
AB  - BACKGROUND: Hyperadrenergic postural tachycardia syndrome (POTS) is the main
      phenotype of POTS. The aim of this study was to present our single-center
      experience of hyperadrenergic POTS in children and adolescents. METHODS: Thirty
      seven patients who met the diagnostic criteria for POTS were enrolled in our
      study. Their orthostatic serum norepinephrine levels were determined by high
      performance liquid chromatography. In a retrospective analysis, based on clinical
      and serum norepinephrine criteria, we analyzed the clinical features of POTS
      cases between the POTS-alone group and the hyperadrenergic POTS group. RESULTS:
      Nineteen patients (51.35%) met the diagnostic criteria for hyperadrenergic POTS
      and 18 patients were assigned to the POTS-alone group. Compared with the POTS
      alone patients, dizziness, headache and tremulousness were more frequent in
      patients with hyperadrenergic POTS (P < 0.05). During the tilt table test,
      children with hyperadrenergic POTS had a greater increment of systolic blood
      pressure and heart rate than POTS-alone patients. CONCLUSION: Patients with
      hyperadrenergic POTS should be identified and differentiated from those with
      neuropathic POTS. Hyperadrenergic POTS in children and adolescents should be
      considered when POTS patients suffer from frequent dizziness, headache, and
      tremulousness. In head-up tilt testing, children and adolescents with hemodynamic
      characteristics of hyperadrenergic POTS had greater increments of systolic blood
      pressure and heart rate.

PMID- 24862637
TI  - CD34 selected cells for the treatment of poor graft function after allogeneic
      stem cell transplantation.
AB  - Poor graft function (PGF) is characterized by pancytopenia and a hypoplastic
      marrow, with complete donor chimerism, usually without severe graft-versus-host
      disease (GVHD). We report 41 patients with PGF, treated with granulocyte colony
      stimulating factor-mobilized CD34 selected cells, at a median interval from
      transplant of 140 days, without conditioning and without GVHD prophylaxis. Donors
      were HLA matched siblings (n = 12), unrelated donors (n = 18), or mismatched
      family members (n = 11). The median number of infused CD34(+) cells was 3.4 *
      10(6)/kg. The rate of trilineage recovery was 75%: 83% for HLA matched siblings
      and 72% for unrelated and mismatched family members (P = .3). The cumulative
      incidence of acute grade II GVHD was 15%, and no patient developed de novo
      chronic GVHD. The actuarial 3-year survival is 63%: 76% and 25% for patients with
      or without trilineage recovery. These data confirm the role of CD34(+) selected
      cells from the same donor in the treatment of PGF and warrant the request for a
      second donation also when the donor is unrelated. 

PMID- 24862640
TI  - Factors that affect readiness to change lifestyle: a 22-country survey from
      primary care.
AB  - BACKGROUND: The family physician's task in prevention is not only an assessment
      of patients' health risks but also counselling individual patients. AIM: Aim of
      this primary care based study was to find how patients' characteristics relate to
      their readiness to change. METHODS: This multinational cross-sectional survey was
      conducted in primary care in 22 European countries, coordinated by EUROPREV.
      Consecutive attenders from randomly selected family practices answered a
      questionnaire about attitudes towards prevention and about lifestyle. RESULTS:
      The questionnaire was answered by 7947 patients in 224 primary care practices in
      22 European countries. Smoking was reported by 828 women (23.2%) versus 1238
      (32.57%) men, unhealthy diet by 637 (11.6%) women versus 830 men (17.62%), risky
      alcohol consumption by 348 women (8.19%) versus 1009 men (23.07%) and the lack of
      physical activity by 617 women (12.68%) versus 614 men (16.45%). The need for
      change was declared by 432 (31.8%) of 1357 risky drinkers, 612 (29.6%) of 2066
      smokers, 1210 (82.4%) of 1467 patients with unhealthy diet and by 2456 (30.9%) of
      all participants, 1231 of them were not physically active at all. Among patients
      with unhealthy dietary habits, 681 (56.3%) were confident of successfully
      changing their behaviour, among physically inactive it was 1561 (63.6 %), among
      smokers 284 (46.4%), and among risky drinkers 214 (49.5%). CONCLUSION: More
      likely to be ready to change unhealthy lifestyles are frequent attenders,
      European Union citizens, women and patients under 50 years of age.

PMID- 24862639
TI  - Molecular dynamics modeling the synthetic and biological polymers interactions
      pre-studied via docking: anchors modified polyanions interference with the HIV-1
      fusion mediator.
AB  - In previous works we reported the design, synthesis and in vitro evaluations of
      synthetic anionic polymers modified by alicyclic pendant groups (hydrophobic
      anchors), as a novel class of inhibitors of the human immunodeficiency virus type
      1 (HIV-1) entry into human cells. Recently, these synthetic polymers interactions
      with key mediator of HIV-1 entry-fusion, the tri-helix core of the first heptad
      repeat regions [HR1]3 of viral envelope protein gp41, were pre-studied via
      docking in terms of newly formulated algorithm for stepwise approximation from
      fragments of polymeric backbone and side-group models toward real polymeric
      chains. In the present article the docking results were verified under molecular
      dynamics (MD) modeling. In contrast with limited capabilities of the docking, the
      MD allowed of using much more large models of the polymeric ligands, considering
      flexibility of both ligand and target simultaneously. Among the synthesized
      polymers the dinorbornen anchors containing alternating copolymers of maleic acid
      were selected as the most representative ligands (possessing the top anti-HIV
      activity in vitro in correlation with the highest binding energy in the docking).
      To verify the probability of binding of the polymers with the [HR1]3 in the sites
      defined via docking, various starting positions of polymer chains were tried. The
      MD simulations confirmed the main docking-predicted priority for binding sites,
      and possibilities for axial and belting modes of the ligands-target interactions.
      Some newly MD-discovered aspects of the ligand's backbone and anchor units
      dynamic cooperation in binding the viral target clarify mechanisms of the
      synthetic polymers anti-HIV activity and drug resistance prevention. 

PMID- 24862638
TI  - Mismatched related and unrelated donors for allogeneic hematopoietic cell
      transplantation for adults with hematologic malignancies.
AB  - Two parallel phase II trials in adults with hematologic malignancies demonstrated
      comparable survival after reduced-intensity conditioning and transplantation of
      either 2 HLA-mismatched umbilical cord blood (UCB) units or bone marrow from HLA
      haploidentical relatives. Donor choice is often subject to physician practice and
      institutional preference. Despite clear preliminary evidence of equipoise between
      HLA-haploidentical related donor and double unrelated donor UCB transplantation,
      the actual prospect of being randomized between these 2 very different donor
      sources is daunting to patients and their treating physicians alike. Under these
      circumstances, it is challenging to conduct a phase III randomized trial in which
      patients are assigned to the UCB or haploidentical bone marrow arms. Therefore,
      we aimed to provide an evidence-based review and recommendations for selecting
      donors for adults without an HLA-matched sibling or an HLA-matched adult
      unrelated donor. 

PMID- 24862641
TI  - Longitudinal assessment of lung area measurements by two-dimensional ultrasound
      in fetuses with isolated left-sided congenital diaphragmatic hernia.
AB  - OBJECTIVE: To evaluate lung growth in healthy fetuses and those with congenital
      diaphragmatic hernia (CDH) using two-dimensional (2D) ultrasound. METHODS: Fetal
      right lung measurements obtained by 2D ultrasound between 19 and 37 weeks'
      gestation were evaluated longitudinally in 66 healthy fetuses and 52 fetuses with
      isolated left-sided CDH. Right lung areas were determined by the 'tracing' and
      'longest-diameters' methods and, subsequently, lung area-to-head circumference
      ratios (LHRs) were calculated. Functions fitted to these size parameters with
      respect to gestational age were evaluated for three sets of group-wise
      comparisons: (1) healthy vs CDH fetuses; (2) different degrees of severity of
      CDH; and (3) CDH fetuses that survived vs those that died by 6 months postpartum.
      RESULTS: There was a significantly slower increase in right lung areas and LHRs
      with advancing gestational age in CDH fetuses than in healthy individuals (P <
      0.05). Compared to those with milder forms of CDH, lung areas and LHRs of fetuses
      with more severe forms displayed a smaller increase (P < 0.05) and LHRs of
      fetuses with severe CDH did not increase during pregnancy (P > 0.05). Individuals
      who died postpartum did not show any increase in LHR (P > 0.05) throughout
      gestation. CONCLUSIONS: The right lung area and LHR, calculated using either the
      longest-diameters or tracing method, display reduced growth rates during
      gestation in cases of isolated left-sided CDH as compared with healthy fetuses.
      The growth curve characteristics of fetal lung areas and LHRs may be useful for
      predicting neonatal mortality.

PMID- 24862642
TI  - Clinical and laboratory indices of severe renal lesions in children with febrile
      urinary tract infection.
AB  - AIM: To evaluate the predictive value of various clinical and laboratory
      parameters on the identification of acute extensive and/or multifocal renal
      involvement in children with febrile urinary tract infections (UTI). METHODS: The
      medical records of 148 children (median age: 2.4 months, range: 11 days-24
      months), who were admitted during a 3-year period with a first episode of febrile
      UTI, were analysed. Acute dimercaptosuccinic acid scintigraphy (DMSA), clinical
      and laboratory parameters were evaluated. RESULTS: Seventy six children (51%) had
      abnormal findings on the acute DMSA. Of them, 20 had DMSA grade 2, while 56 had
      grade 3 and 4. Patients with a DMSA grade 3 and 4 were more likely to have
      shivering (OR 3.4), white blood count (WBC) >= 18 000/MUL (OR 2.4), absolute
      neutrophil count (ANC) >= 9300/MUL (OR 4.4), C-reactive protein (CRP) >= 50 mg/L
      (OR 2.7) and procalcitonin (PCT) >= 1.64 ng/mL (OR diagnostic). There was a
      significant difference of WBC (p = 0.004), ANC, CRP and PCT levels (p < 0.001)
      between children with normal and grade 2 aDMSA versus those with aDMSA grade 3
      and 4. CONCLUSIONS: Shivering and elevated inflammatory markers increase the risk
      of acute extensive and/or multifocal kidney involvement in children with febrile
      UTI. Procalcitonin seems to be an excellent marker of the severity of acute
      parenchymal involvement.

PMID- 24862643
TI  - Growth of large-scale nanotwinned Cu nanowire arrays from anodic aluminum oxide
      membrane by electrochemical deposition process: controllable nanotwin density and
      growth orientation with enhanced electrical endurance performance.
AB  - Densely nanotwinned Cu nanowire (NW) arrays with an identical diameter of ~55 nm
      were fabricated by pulse electrochemical deposition at low temperature using
      anodic aluminum oxide as a template. Different growth orientations of nanotwinned
      Cu nanowire arrays were investigated. The endurance of the electrical current
      density before breakdown of the nanotwinned Cu NWs can reach up to 2.4 * 10(8) A
      cm(-2). The formation of highly dense nanotwins is attributed to relaxation of
      coalescence induced stress and twin fault stacking when Cu NWs grow by two
      dimensional kinetics. A mechanism based on the twinning structure effect on the
      electromigration was proposed to explain the improved electrical endurance of Cu.
      The result demonstrates that the formation of nanotwins into Cu NWs can
      effectively suppress the void growth, leading to extended life time for use in
      electronic devices. 

PMID- 24862644
TI  - Transition-metal-ion-mediated polymerization of dopamine: mussel-inspired
      approach for the facile synthesis of robust transition-metal nanoparticle
      graphene hybrids.
AB  - Inspired by the high transition-metal-ion content in mussel glues, and the cross
      linking and mechanical reinforcement effects of some transition-metal ions in
      mussel threads, high concentrations of nickel(II), cobalt(II), and manganese(II)
      ions have been purposely introduced into the reaction system for dopamine
      polymerization. Kinetics studies were conducted for the Ni(2+)-dopamine system to
      investigate the polymerization mechanism. The results show that the Ni(2+) ions
      could accelerate the assembly of dopamine oligomers in the polymerization
      process. Spectroscopic and electron microscopic studies reveal that the Ni(2+)
      ions are chelated with polydopamine (PDA) units, forming homogeneous Ni(2+)-PDA
      complexes. This facile one-pot approach is utilized to construct transition-metal
      ion-PDA complex thin coatings on graphene oxide, which can be carbonized to
      produce robust hybrid nanosheets with well-dispersed metallic nickel/metallic
      cobalt/manganese(II) oxide nanoparticles embedded in PDA-derived thin graphitic
      carbon layers. The nickel-graphene hybrid prepared by using this approach shows
      good catalytic properties and recyclability for the reduction of p-nitrophenol.

PMID- 24862646
TI  - Correlation of CD4 counts with the FNAC patterns of tubercular lymphadenitis in
      patients with HIV: a cross sectional pilot study.
AB  - BACKGROUND: Fine needle aspiration cytology (FNAC) of TB lymphadenitis (TBL) in
      HIV shows four different patterns, which may be reflective of immune status. We
      hypothesize that the CD(4) counts, a marker of immunologic status, correlates
      with FNAC morphology of TBL. This study was undertaken to compare the mean CD(4)
      counts across the different cytology patterns and to correlate the CD(4) counts
      with FNAC patterns in these patients. METHODS: Forty newly diagnosed HIV patients
      with TBL on FNAC (10 in each pattern) were selected by convenient sampling based
      on inclusion exclusion criteria. The CD(4) counts were obtained in these
      patients. Its correlation with different FNAC patterns was assessed using SPSS
      version 16. RESULTS: Analysis of covariance showed significant difference in the
      mean CD(4) counts between all the four patterns [F (374), df (3), P-value =
      0.000]. Spearman's correlation analysis showed significant correlation of CD(4)
      counts with the FNAC patterns (correlation coefficient of 0.967; P-value of 0.01)
      with pattern 1 having low CD(4) counts and pattern 4 having high CD(4) counts.
      CONCLUSION: CD(4) counts show significant correlation with FNAC patterns of TBL
      in HIV patients. Pattern 1, suggestive of poor immunological response (chiefly
      necrosis, occasional ill defined granuloma, AFB 3+) had low CD(4) counts, while
      pattern 4, suggestive of good immunological response (well defined granuloma, no
      necrosis and AFB 1+), had high CD(4) counts. Thus FNAC patterns may be used to
      predict the CD(4) counts in HIV patients where CD(4) facilities are not available
      or vice versa.

PMID- 24862645
TI  - Clinical-MRI correlations in a multiethnic cohort with recent lacunar stroke: the
      SPS3 trial.
AB  - BACKGROUND: Neuroimaging manifestations of small vessel disease are
      heterogeneous, and correlation with patient features has not been adequately
      characterized. AIM: Our goal was to correlate magnetic resonance imaging findings
      with clinical features in a large multiethnic cohort with recent lacunar stroke.
      METHODS: Patient characteristics were correlated with neuroimaging results in the
      Secondary Prevention of Small Subcortical Stroke study participants. RESULTS:
      Among 3005 patients, mean age was 63 years; 62% were men; and 51%, 30%, and 16%
      were non-Hispanic White, Hispanic, and Black, respectively. Recent lacunar
      infarcts were distributed between the subcortical hemisphere (31%), thalamus
      (26%), brainstem/cerebellum (26%), and basal ganglia/internal capsule (16%).
      Multiple lacunar infarcts (i.e., acute and remote) were present in 40% and
      associated with increased age (OR 1.3 per 20 years, 95% CI 1.1, 1.5), male gender
      (OR 1.5, CI 1.3, 1.7), hypertension (OR 1.5, CI 1.2, 1.8), increased systolic
      blood pressure (OR 1.2 per 20 mmHg, CI 1.1, 1.3), and prior stroke (OR 3.8, CI
      2.9, 5.0). Moderate-severe white matter hyperintensities were present in 50% and
      associated with increased age (OR 4.3 per 20 years, CI 3.4, 5.4), hypertension
      (OR 1.8, CI 1.4, 2.3), increased systolic blood pressure (OR 1.3 per 20 mmHg, CI
      1.1, 1.5), increased diastolic blood pressure (OR 1.2 per 10 mm, CI 1.0, 1.3),
      and prior stroke (OR 3.3, CI 2.3, 4.5). Infarct location varied significantly by
      race-ethnicity (P < 0.001), with Blacks and Hispanics having more infarcts in the
      brainstem/cerebellum than non-Hispanic Whites, and by gender with women more
      often having thalamic lacunes than men (P <= 0.001). CONCLUSIONS: In patients
      with recent lacunar stroke, infarct location and number have distinctie
      associations with gender, vascular risk factors, and race-ethnicity,
      demonstrating the complex pathogenesis of lacunar stroke and cerebral small
      artery disease.

PMID- 24862647
TI  - Expression of group XIIA phospholipase A2 in human digestive organs.
AB  - Cellular distribution of group XIIA phospholipase A2 (GXIIA PLA2) was studied in
      human digestive organs by immunohistochemistry. GXIIA PLA2 protein was detected
      in epithelial cells of normal gastrointestinal tract, gallbladder and pancreatic
      acinar cells. The GXIIA PLA2 protein was evenly distributed in the cytoplasm in
      contrast to secretory granular distribution of GIB PLA2 and GIIA PLA2 in
      pancreatic acinar cells and small intestinal Paneth cells respectively.
      Epithelial cells of intestinal glands in Crohn's disease and ulcerative colitis
      expressed abundant GXIIA PLA2 , whereas inflammatory cells were devoid of the
      enzyme protein. Tumour cells in colonic adenomas and carcinomas and pancreatic
      ductogenic carcinomas expressed GXIIA PLA2 protein at varying intensity levels.
      The putative functions of GXIIA PLA2 remain to be investigated and its role in
      healthy and diseased digestive organs can only be speculated on at present.

PMID- 24862649
TI  - Synthesis of new diorganodiselenides from organic halides: their
      antiproliferative effects against human breast cancer MCF-7 cells.
AB  - A new series of bis(aryl or aralkyl) diselenides 5a-5q was synthesized by
      selenylation from aryl halide (or aralkyl halide) for development of new
      anticancer agents. The process involves the reaction of aryl halides (or aralkyl
      halides) with selenium, hydrazine hydrate under atmospheric pressure in the
      presence of sodium hydroxide, to afford diorganodiselenides. These new compounds
      showed antiproliferative activities against breast cancer (MCF-7) cells in CCK-8
      assays, and could be promising candidates for chemotherapy of carcinomas. Among
      17 synthesized compounds for inhibiting the growth of these cell lines, 1,2
      bis(chloropyridazinyl) diselenide 5a showed the highest potency. This result
      suggests the potential anticancer activity of compound 5a. 

PMID- 24862648
TI  - Osteoclast fusion is based on heterogeneity between fusion partners.
AB  - Bone-resorbing osteoclasts are formed through fusion of mononucleated precursors.
      Their choice of partners during the fusion process remains unclear. We
      hypothesized that osteoclasts are selective in their choice of fusion partner and
      that this selectivity is based on heterogeneity among the cells with respect to
      their maturation stage and their expression and cellular organization of fusion
      factors. Support for this hypothesis was found from immunofluorescence staining
      of the osteoclast fusion factors CD47, dendritic cell-specific transmembrane
      protein (DC-STAMP), and syncytin-1. These stainings revealed heterogeneous
      localization patterns of all three factors within a given culture of osteoclasts.
      CD47 was found to be localized primarily in small osteoclasts and preosteoclasts,
      which were also positive for DC-STAMP but negative for cathepsin K expression. A
      role of CD47 in the early osteoclast fusion steps was also suggested from
      experiments with a CD47 blocking antibody, which resulted in an inhibition of the
      fusion of small osteoclasts. Conversely, blocking of connexin 43 affected the
      fusion of larger osteoclasts with four or more nuclei. The suggestion that
      different fusion factors function at different stages of osteoclast fusion
      supports the idea of heterogeneity in the osteoclast population; our results
      suggest that osteoclast fusion is indeed based on heterogeneity. Considering the
      in vivo environment in which osteoclasts develop and fuse, our findings seem very
      applicable and provide novel, important insight into key issues in bone and
      fusion research.

PMID- 24862650
TI  - Molecular imaging monitoring of poly(ethylene glycol) conjugated islets for
      evaluation of islet graft rejection.
AB  - It is important to chase the function of islet after transplantation. Thus, we
      examined the correlation between grafted islets function and molecular imaging
      intensity using Cy5.5 labeled islet. The ability of Cy5.5-PEG-NHS to chemically
      bind on the surface of islets was determined by confocal laser scanning
      microscope. Then, fluorescence intensity of different number of Cy5.5 labeled
      islets was determined using optical imaging system. We have found out the
      intensity of fluorescence increased with increasing the total number of islet in
      each well. In addition, different number of Cy5.5-labeled islet has been
      transplanted into the athymic mice for in vivo imaging. The intensity emitted
      from Cy5.5-labeled islets augmented proportionally with increased number of
      transplanted islets. To understand the correlation between the function of
      grafted islet and the fluorescence intensity emitted optical imaging system,
      Cy5.5-labeled islets have been transplanted into F344 rats. The results revealed
      that there was a correlation between the fluorescence intensity and the non
      fasting blood glucose (NBG) levels of islets received rats. Strong fluorescence
      intensity corresponded to low NBG whereas low signal was associated to high NBG.
      In conclusion, the fluorescence intensity emitted from Cy5.5-labeled islets can
      be used as a marker of cells viability and functionality after transplantation. 

PMID- 24862651
TI  - Constituents from Zhuyeqing Liquor with hepatoprotective effect on alcohol
      induced HepaG 2 toxicity.
AB  - An unprecedented new skeleton compound (1R, 10R, 11S)-10,11-dimethyl-4-formyl-2,9
      dioxa-bicyclo [5.4.0] undeca-4,6-dien-3-one (1), monoterpenoids and monoterpene
      glycoside picrocrocinic ester (2), epijasminoside B (3) and 6'-O-(3-methoxyl-4
      hydroxyl-coumaroyl)-epijasminoside B (4), along with 26 known compounds, were
      obtained from Zhuyeqing Liquor. These compounds were identified mainly by
      analyzing their NMR, HR-ESI-MS and CD data. The isolated compounds were screened
      against alcohol induced HepaG 2 toxicity for hepatoprotective assay. Compounds
      10, 19, 21 and 26 displayed the highest potency against alcohol induced HepaG 2
      toxicity with the cell viability ratio 41.21, 56.91, 67.69 and 70.32%
      respectively.

PMID- 24862652
TI  - Density functional theory simulation of hydrogen-bonding structure and
      vibrational densities of states at the quartz (101)-water interface and its
      relation to dissolution as a function of solution pH and ionic strength.
AB  - Two hypotheses for the dissolution of SiO2 in ionic solutions are investigated
      via ab initio molecular dynamics (AIMD) simulations. The hypotheses are (1) that
      the presence of ions induces orientations in H2O molecules at the surface, which
      favor proton transfer to bridging oxygen (BO) atoms, and (2) the presence of ions
      induces stronger H-bonding between terminal hydroxyl (TH) groups and BO atoms,
      allowing proton transfer. It is found that the model structures produced by
      density functional theory simulations do not support the former hypothesis and
      are more consistent with the latter. 

PMID- 24862653
TI  - New methods of human-robot interaction in medical practice.

PMID- 24862654
TI  - The verbal fluency index: Dutch normative data for cognitive testing in ALS.
AB  - OBJECTIVE: Executive dysfunction occurs in 30-50% of amyotrophic lateral
      sclerosis (ALS) patients and is most frequently assessed with the verbal fluency
      test. The verbal fluency index (VFI) has been developed to correct for slowness
      of speech in ALS, and reflects the average thinking time per word. However, its
      use as a marker of cognitive impairment is hindered by the absence of valid norm
      scores. Therefore, we provide normative data for the VFI. METHODS: Dutch
      volunteers were demographically matched to the Dutch ALS population and completed
      the verbal fluency index (one-minute and three-minute spoken letter fluency).
      Multiple stepwise linear regression was performed to assess the influence of
      demographic variables, past medical history and medication use. RESULTS: 273
      volunteers participated in this study. Educational level was negatively
      correlated to one-minute and three-minute VFI performance (r = -0.3 and r = -0.4,
      p < 0.001, respectively). No correlations for age, gender, medication and past
      medical history were found. A formula for standardized z-scores, corrected for
      educational level, for the one-minute and three-minute VFI was calculated.
      CONCLUSIONS: We provide Dutch normative data for the spoken verbal fluency index,
      which can be used internationally, but validation in other languages is
      recommended. The findings illustrate the importance of valid disease-specific
      norm scores for time-dependent cognitive tests in ALS.

PMID- 24862655
TI  - Femoral nerve block for pain relief in hip fracture: a dose finding study.
AB  - Hip fracture is the most common orthopaedic emergency. We investigated the
      concentration of 30 ml levobupivacaine that provided analgesia to 50% and 95% of
      patients with a hip fracture when injected around the femoral nerve under
      ultrasound guidance. We defined analgesia as a >= 20-point decrease on a 100
      point pain scale with reduced cold sensation in the middle third of the anterior
      thigh 30 min after the nerve block. We increased the concentration of
      levobupivacaine if the preceding dose had been ineffective and decreased it if
      the preceding dose had been effective. Probit regression modelling estimated the
      effective (95% CI) concentration of 30 ml levobupivacaine in 50% and 95% of
      patients with a fractured hip to be 0.026 (0.023-0.028)% w/v and 0.036 (0.027
      0.047)% w/v, respectively. 

PMID- 24862656
TI  - MEFV mutations in Egyptian children with systemic-onset juvenile idiopathic
      arthritis.
AB  - BACKGROUND AND OBJECTIVES: Systemic-onset juvenile idiopathic arthritis (SoJIA)
      is a chronic auto-inflammatory disease of childhood, with a complex genetic
      trait, which is characterized by arthritis associated with systemic
      manifestations. Familial Mediterranean fever (FMF) is another auto-inflammatory
      disorder that is monogenic. There are speculations as to whether Mediterranean
      fever (MEFV) mutations are among the genetic determinants of SoJIA. Our aim was
      to explore the frequency and clinical significance of MEFV mutations in Egyptian
      SoJIA patients. A group of healthy children were assigned to the control group in
      an attempt to estimate the carrier rate of MEFV mutations in Egypt. METHODS:
      Eighty-four children were recruited in this study; 54 children, age (mean +/-
      standard deviation; 8.31 +/- 2.85 years), diagnosed as having SoJIA with no
      typical symptoms of FMF; 30 healthy age- and gender-matched children served as
      the control group. All recruited children were screened for 12 common MEFV
      mutations using a reverse hybridization assay of biotinylated PCR products.
      RESULTS: SoJIA patients had a significantly higher frequency of MEFV mutations
      (66.7 %) than in the healthy control population (16.7 %). V726A was the leading
      mutation in SoJIA patients, with an allelic frequency of 15.74 %, followed by
      E148Q, with an allelic frequency of 7.4 %. Children who were carriers of MEFV
      mutations had an 18 times higher risk of developing SoJIA than wild-type carriers
      [odds ratio 18.0 (95 % CI 5-69), P < 0.01]. E148Q was the leading mutation,
      present in 13.3 % of healthy controls. CONCLUSION: These findings suggest that
      MEFV mutations may be responsible for auto-inflammatory diseases other than FMF,
      and patients with SoJIA, especially those with a positive family history of FMF
      or SoJIA, should be screened for MEFV mutations in countries where FMF is
      frequent.

PMID- 24862659
TI  - Loneliness and social behaviours in a virtual social environment.
AB  - Feeling lonely motivates people to reconnect with others, but it can also trigger
      a vicious cycle of cognitions and behaviours that reinforces their loneliness. In
      this study, we examined the behavioural consequences of loneliness in a virtual
      social environment. A total of 176 participants navigated a character
      (protagonist) through a two-dimensional browser game and rated the character's
      loneliness multiple times during the game. In the first part of the game, another
      character is introduced as the protagonist's spouse. At one point, the spouse
      leaves for an undetermined period of time but later returns. Immediately before
      this separation, higher ascribed loneliness of the protagonist was associated
      with more frequent interactions with the spouse. After the reunion, however,
      higher ascribed loneliness was associated with less frequent interactions with
      the spouse. Ascribed loneliness was not significantly related to the frequency of
      interactions with others nor to the frequency of solitary activities. These
      patterns held after controlling for ascribed positive affect. Participants'
      levels of loneliness were related to the level of ascribed loneliness only when
      the spouse was present but not when the spouse was absent. In sum, these findings
      suggest that the conditions that trigger the vicious cycle of loneliness are
      person- and situation-specific. 

PMID- 24862658
TI  - [Regadenoson as a new stress agent in myocardial perfusion imaging. Initial
      experience in The Netherlands].
AB  - OBJECTIVE: Regadenoson is a recently approved selective adenosine-2A receptor
      agonist to induce pharmacological stress in myocardial perfusion imaging (MPI)
      procedures using a single bolus injection. MATERIAL AND METHODS: We included 123
      patients referred for MPI because of suspected coronary arterial disease (CAD).
      Of these, 66 patients underwent a regadenoson stress test and 57 patients
      underwent an adenosine stress test preceding standard myocardial SPECT imaging.
      Technicians, physicians and patients were asked to report their experience using
      questionnaires. RESULTS: As compared to adenosine, regadenoson did not produce
      any atrio-ventricular block (0 vs. 10% with adenosine), but did produce minor
      tachycardia and minimal blood pressure changes while all other side effects were
      milder and shorter. There were fewer patients with severe complaints after taking
      regadenoson than adenosine (17% vs. 32%, respectively, p<0.01). The most frequent
      complaint reported was dyspnea, followed by flushing and chest pain. However,
      when they did occur, they usually disappeared rapidly. The overall symptom score,
      including severity and duration of side effects, was significantly lower after
      regadenoson than after adenosine (6.7+/-6.3 vs. 10.0+/-7.9, respectively;
      p<0.01.) SPECT imaging results were similar. The regadenoson procedure was faster
      and more practical. CONCLUSION: Regadenoson, the new selective adenosine-2A
      receptor agonist, is a stress agent for MPI with a patient- and department
      friendly profile.

PMID- 24862657
TI  - Inflammatory mediators of cognitive impairment in bipolar disorder.
AB  - OBJECTIVES: Recent studies have pointed to neuroinflammation, oxidative stress
      and neurotrophic factors as key mediators in the pathophysiology of mood
      disorders. Little is however known about the cascade of biological episodes
      underlying the cognitive deficits observed during the acute and euthymic phases
      of bipolar disorder (BD). The aim of this review is to assess the potential
      association between cognitive impairment and biomarkers of inflammation,
      oxidative stress and neurotrophic activity in BD. METHODS: Scopus (all
      databases), Pubmed and Ovid Medline were systematically searched with no language
      or year restrictions, up to November 2013, for human studies that collected both
      inflammatory markers and cognitive data in BD. Selected search terms were bipolar
      disorder, depression, mania, psychosis, inflammatory, cognitive and neurotrophic.
      RESULTS: Ten human studies satisfied the criteria for consideration. The findings
      showed that high levels of peripheral inflammatory-cytokine, oxidative stress and
      reduced brain derived neurotrophic factor (BDNF) levels were associated with poor
      cognitive performance. The BDNF val66met polymorphism is a potential
      vulnerability factor for cognitive impairment in BD. CONCLUSIONS: Current data
      provide preliminary evidence of a link between the cognitive decline observed in
      BD and mechanisms of neuroinflammation and neuroprotection. The identification of
      BD specific inflammatory markers and polymorphisms in inflammatory response genes
      may be of assistance for therapeutic intervention.

PMID- 24862660
TI  - Intraoperative radiation therapy with electrons in breast cancer conservative
      treatment: our experience.
AB  - Radiotherapy plays a central role in the local control of breast cancer following
      conservative surgery, representing the standard treatment for patients undergoing
      quadrantectomy or lumpectomy and consisting in 5 or 6 weeks of treatment with a
      total dose of 45-50 Gy. In the last ten years new trends in radiation therapy
      have been developing with a new planning of duration and extension of breast
      tissue to irradiate. Moreover some authors presented the idea of combining the
      use of intraoperatory radiotherapy with the partial breast irradiation, with the
      aim of irradiate the breast in a single session during breast conserving surgery.
      From September 2009 to July 2010 we prospectively enrolled 13 patients to undergo
      electron beam intraoperative radiotherapy after breast conservative treatment for
      early breast cancer. At a mean follow-up of 46 months no local recurrences have
      been described and no patients presented distant metastasis or died for any
      cause. 6 patients (46.2%) presented complications, as fibrosis and liponecrosis.
      Our results suggest that electron beam intraoperative radiotherapy in the
      conservative treatment of breast cancer could be considered a suitable option for
      low risk patients, even if our sample is very small and we need longer follow-up
      to draw conclusive results. 

PMID- 24862661
TI  - Trocar site hernia after bariatric surgery: our experience without fascial
      closure.
AB  - INTRODUCTION: The spreading of laparoscopic surgery has increased the occurrence
      of trocar site hernias, along with their related complications. Bariatric surgery
      combines two important risk factors in hernia formation: obesity and complexity
      of port-site closure. Several techniques and devices have been proposed to close
      the trocar wounds to minimize the risk of hernia occurrence. MATERIALS AND
      METHODS: The records of 624 obese patients who underwent laparoscopic bariatric
      procedures between January 2006 and December 2012 were retrospectively reviewed.
      In no patient was performed the closure of the fascial layers of trocar
      incisions. Weight, BMI, E%WL and onset of complications were monthly collected
      for the first year after the procedure, then every six month. RESULTS: 10
      patients showed trocar site hernia, for an overall prevalence of 1.6%. The mean
      time of occurrence was 15 months. None developed intestinal obstruction or other
      complications as a consequence of the hernia. The mean time of follow-up was 54
      months. The mean weight and BMI before interventions were 136.3 +/- 17.7 kg and
      46.0 +/- 4.6 kg/m2 respectively. The mean percentage of excess weight loss (E%WL)
      at one year was 45.9%. CONCLUSION: We avoided complicating the wound closure with
      fascia closure, accepting the risks related to the BMI. So far our procedure for
      port-site closure is relatively simple, safe, less invasive, less time-consuming
      and costless. These advantages could arise from the fact that our patients
      benefit from a remarkable weight loss after the intervention thus reducing one of
      the most important risk factors in the onset of trocar site hernia.

PMID- 24862663
TI  - Early biomarkers of hypocalcemia following total thyroidectomy.
AB  - Hypocalcemia is the most frequent major complication following total
      thyroidectomy (TT), delaying timely hospital demission. We prospectively
      evaluated the diagnostic utility of parathyroid hormone (PTH) measured one hour
      after TT and the delta (post-minus pre-surgery) PTH in order to determine which
      biomarker best predicted post-surgery hypocalcemia. Ninety-six consecutive
      patients, with either plurinodular goiter, Graves' disease or cervico-mediastinal
      goiter (22 (23%) men and 74 (77%) women, mean age 48.5 +/- 15.2 and 47.9 +/- 13.2
      years, respectively), scheduled to undergo TT were enrolled. PTH was measured
      prior and one hour after surgery. Delta PTH was defined as one-hour post-surgery
      values minus pre-surgery PTH level. Hypocalcemia was defined as a calcemia under
      8.0 mg/dL. Receiver operating characteristic (ROC) analysis was used to evaluate
      the Area Under Curve (AUC), sensibility and specificity of the two biomarkers for
      the occurrence of hypocalcemia. Forty-nine (51%) patients presented biochemical
      values under the cut-off but only 17 (18%) had clinical symptoms. Both variables
      yielded statistically significant AUC (PTH one-hour post surgery: 0.654; p =
      0.0403; 95%CI: 0.519-0.773 and delta PTH: 0.659; p = 0.0263; 95%CI: 0.527-0.776).
      Although comparison of the two ROC curves did not yield significant differences,
      delta PTH yielded a better sensitivity and PTH one-hour post-TT yielded a
      marginally better specificity (sensitivity of 50% and 87% and specificity of 76%
      and 67% for cut-offs of <39.8 pg/dl and <54.5 pg/dl, respectively). Both
      biomarkers have similar diagnostic accuracy for hypocalcemia, and can be used to
      indicate when supplemental therapy should be implemented in order to favor a
      timely discharge. 

PMID- 24862662
TI  - Central neck dissection in papillary thyroid carcinoma: results of a
      retrospective study.
AB  - AIMS OF THE STUDY: The aim of this retrospective study was to appraise the impact
      of central neck dissection (CND) when treating papillary thyroid carcinoma (PTC)
      and identifying predictors of tumour recurrence by analysing the results and
      complications related to this surgical procedure. MATERIALS AND METHODS: The
      study examined the histories of 347 patients with PTC, divided into two groups:
      group A including 284 patients who underwent total thyroidectomy (TT) only; group
      B including 63 patients who underwent TT and CND and possible lateral neck
      dissection (LND). RESULTS: The patients in the B group were younger than those in
      the A group (an average of 44.5 vs. 48.6; p = 0.03) and their tumours were larger
      (1.91 cm vs 1.27 cm, p = 0.001). Multifocality, extra-capsular extensions of the
      neoplastic mass and high cell histological variant were more prevalent in the B
      group. The incidence of permanent hyperparathyroidism was higher in group B than
      in group A (25.4% vs 9.5%, p = 0.0006). Recurrence of disease and the numbers
      requiring reoperation were also higher in group B: (24.1% in group B vs 6.6 in
      group A, p < 0.0001). Patients classified as clinically N0 at their first
      operation and who were most probably clinically N1, totalled 6.6%. CONCLUSIONS:
      Our data show that only extra-capsular extension may be considered a predictor of
      recurrence. The findings of our study support the idea of carrying out
      "therapeutic" CND only in cases of preoperative or macroscopic intraoperative
      clinical evidence of lymph-node involvement.

PMID- 24862664
TI  - Unusual breast lesion mimicking cancer: diabetic mastopathy.
AB  - Diabetic mastopathy represents an uncommon tumor-like proliferation of fibrous
      tissue of the breast that usually occurs in patients who suffered from type 1
      diabetes mellitus for a long time. We report an uncommon case of diabetic
      mastopathy presenting in a type 2 non-insulin dependent diabetes mellitus 61-year
      old postmenopausal woman. Physical examination revealed a hard, low movable mass
      in the upper outer quadrant of the right breast. Mammography and ultrasonography
      showed typical features of breast cancer. Ultrasound-guided fine-needle
      aspiration cytology (US-FNAC) was performed showing inflammatory infiltrate,
      suggesting excisional biopsy. Histological findings demonstrated typical diabetic
      mastopathy with fibrosis, histiocytic and limphocytic infiltration without
      evidence of malignancy. 

PMID- 24862665
TI  - The role of 68-Ga-DOTATOC CT-PET in surgical tactic for gastric neuroendocrine
      tumors treatment: our experience: a case report.
AB  - Gastric neuroendocrine tumors (g-NETs), which originate from gastric
      enterochromaffin-like (ECL) mucosal cells and account for 2.4% of all carcinoids,
      are increasingly recognized due to expanding indications of upper
      gastrointestinal endoscopy. Often silent and benign, g-NETs may however, be
      aggressive and sometimes they mimic the course of gastric adenocarcinoma. Current
      nosography distinguishes those occurring in chronic conditions with
      hypergastrinemia, as the type 1 associated with chronic atrophic gastritis, and
      the type 2 associated with Zollinger-Ellison syndrome in MEN1. Conversely, type 3
      and 4 (according to some authors) are unrelated to hypergastrinemia and are
      frequently malignant, with a propension to develop distant metastases. While
      there is a general agreement concerning the treatment of malignant gastric
      neuroendocrine tumors, for types 1 and 2, current possibilities include
      surveillance, endoscopic polypectomy, surgical excision, associated or not with
      surgical antrectomy, or total gastrectomy. This report, based on our clinical
      experience, discusses how the size, number, depth, histological grading, staging
      with CT, MRI, and the use of recently developed somatostatin receptor tracers
      (68Ga-DOTATATE, 68Ga-DOTA-TOC) could allow the correct identification of a benign
      or malignant propensity of an individual tumor, thus avoiding underestimation or
      overtreatment of these uncommon neoplasms. 

PMID- 24862666
TI  - Laparoscopic adrenalectomy for large adrenal masses: single team experience.
AB  - INTRODUCTION: Laparoscopic adrenalectomy is today considered the standard
      treatment for benign small adrenal tumors. An open question is the use of
      laparoscopy for large adrenal masses because of technical limitations and
      increased risk of malignancy. In this study we report our experience in
      laparoscopic adrenalectomy for adrenal masses larger than 6 cm. METHODS: Between
      January 2010 and December 2013 we performed 41 laparoscopic adrenalectomy.
      Fourteen of 41 patients (34,1%) were submitted to laparoscopic adrenalectomy for
      lesion >6 cm in size. All patients were submitted routinely to radiological and
      hormonal tests to indentify tumors characteristics. RESULTS: The patients treated
      were 9 male and 5 female, the mean age was 55.6 years (range 38-74). The mean
      tumor size was 8.2 cm (range 6-14 cm) and the lesion were localized on right side
      in 8 patients and on the left side in 6 patients. The mean operative time was 181
      min (range 145-240 min). Mean blood loss was 90 ml. No conversion to open surgery
      was required. CONCLUSION: Laparoscopic adrenalectomy offers better surgical
      outcomes than open adrenalectomy. Size criteria are, at the moment, the main
      subject discussed for the laparoscopic approach to adrenal tumors. In fact, size
      is an important variable in predicting malignancy. This experience and the
      results of literature suggest that laparoscopic approach is safe and feasible for
      adrenal masses larger than 6 cm with a longer operative time. In presence of
      local invasion or vascular infiltration laparoscopy is contraindicated.

PMID- 24862668
TI  - Role of intraoperative neuromonitoring of recurrent laryngeal nerves in the
      outcomes of surgery for thyroid cancer.
AB  - INTRODUCTION: The aim of this retrospective study was to evaluate the ability of
      intraoperative neuromonitoring to predict the postoperative functional outcome
      and its role in reducing the postoperative recurrent laryngeal nerve palsy rate
      during thyroidectomy for thyroid malignancy. METHODS: Between June 2007 and March
      2013, 656 consecutive patients with thyroid cancer underwent thyroidectomy by a
      single surgical team. We compared 357 patients who have had neuromonitoring
      (Group A) to 299 patients who have undergone surgery with nerve visualization
      alone (group B). RESULTS: In group A 7 recurrent laryngeal nerve paralysis were
      observed (1.96%), 6 (1.68%) transient and 1 (0.28%) permanent; a bilateral
      recurrent laryngeal palsy was observed in 1 of the 7 cases (0.28%). In group B 6
      recurrent laryngeal nerve paralysis were observed (2.01%), 5 (2.01%) transient
      and 1 permanent (0.33%); bilateral palsy was observed in 1 of the 6 cases
      (0.33%). Differences were not statistically significative. CONCLUSIONS: Routine
      visual nerve identification remains the gold standard of recurrent laryngeal
      nerve management in surgery for thyroid cancer. Intraoperative neuromonitoring is
      safe, effective, reliable, and easy to perform in excluding postoperative
      recurrent laryngeal palsy. It helps to identify the nerve in thyroid cancer, but
      it did not decrease the injuries compared with visualization alone in this study;
      however, its use can change the operative strategy in order to prevent the risk
      of bilateral damage in case of signal loss. Future studies are needed to evaluate
      the benefit of intraoperative neuromonitoring in thyroidectomy for thyroid
      cancer.

PMID- 24862667
TI  - Imaging of adrenal incidentaloma: our experience.
AB  - PURPOSE: To investigate clinical, biochemical and radiological features in 35
      patients with adrenal incidentaloma found on CT and/or MRI and to define the
      management of patients with adrenal masses. MATHERIAL AND METHODS: From January
      2011 and May 2013, 35 patients (19F, 16M) with an adrenal mass incidentally
      discovered on CT and/or MRI were enrolled in a retrospective study. Thirthy-two
      patients underwent MDCT and eight 1.5 MRI. RESULTS: Patients consisted in 16
      males and 19 females, aged between 25 and 89 yo. Adrenal lesions were most
      commonly found in the sixth decade; in relation to the side of the mass, 20 were
      found on left side, 15 on the right. Of all the mass analyzed, 3 were <1 cm
      diameter, 29 between 1 and 4 cm, 3 > 4 cm. The most common finding on CT was
      adenoma-like appearance (19 cases in relation to size, 14 in relation to
      attenuation values). Hormonal analysis showed 32 cases of nonfunctional masses
      and 3 cases of hormone activity. Adrenalectomy was performed in ten patients
      having adenoma (5 cases), malignant lesions (2 cases), pheocromocitoma, cyst and
      myelolipoma (1 case). CONCLUSION: Diagnostic approach to adrenal incidentaloma is
      focused on the definition of malignancy and hormonal activity; the
      characterization is needs hormonal and radiological (CT and/or MRI) evaluation,
      even if a fine needle aspiration is needed in selected cases. Benign and/or non
      hypersecreting hormone lesion with <4 cm diameter could be sent to follow-up;
      active adrenal tumors or >4 cm diameter lesions with malignancy suspicious or
      growth during follow-up could be treated with surgical adrenalectomy.

PMID- 24862670
TI  - Long-term outcomes of laparoscopic adrenalectomy for Cushing disease.
AB  - INTRODUCTION: In the surgical management of the patients with Cushing syndrome
      (CS), minimal invasive adrenalectomy (MA) has become the procedure of choice to
      treat adrenal tumors with a benign appearance <=6 cm in diameter. Authors
      evaluated medium- and long-term outcomes of laparoscopic adrenalectomy (LA) for
      CS or subclinical CS (sCS), performed for ten years in an endocrine surgery unit.
      METHODS: We retrospectively reviewed 21 consecutive patients undergone LA for CS
      or sCS from 2003 to 2013. Postoperative clinical and cardiovascular status
      modifications and surgical medium and long-term outcomes were analyzed. RESULTS:
      In each patient surgery determined a normalization of the hormonal profile. There
      was no mortality neither major post-operative complications. Mean operative time
      was higher during the learning curve, there was no conversion, and morbidity rate
      was 6.3%. Regression of the main clinical symptoms occurred slowly in twelve
      months. CONCLUSIONS: LA is a safe, effective and well-tolerated procedure for the
      treatment of CS and sCS reducing arterial blood pressure, body weight and fasting
      glucose levels. Following the learning curve a morbidity rate similar to that
      reported in the MA series for other adrenal diseases is observed.

PMID- 24862669
TI  - Emerging molecular markers for the prognosis of differentiated thyroid cancer
      patients.
AB  - Epithelial thyroid cancers are represented by the differentiated papillary and
      follicular thyroid carcinomas which, following dedifferentiation, are thought to
      give rise to the highly aggressive and incurable anaplastic thyroid carcinomas.
      Although derived from the same cell type, the different thyroid tumors show
      specific histological features, biological behavior and degree of differentiation
      as a consequence of different genetic alterations. Over the last few years, our
      knowledge regarding the molecular alterations underlying thyroid cell malignant
      transformation and cancer progression has considerably increased; however, the
      prognosis of differentiated thyroid cancer patients still relies on high-risk
      clinic-pathological variables. In particular, the actual staging systems provides
      only a rough prediction for cancer mortality and risk of recurrences, including
      in each risk group patients with highly different tumor-specific progression,
      disease-free interval and survival time. In order to improve DTC patient's risk
      stratification, both the European and the American Thyroid Associations proposed
      practical guidelines to integrate the actual staging systems with additional
      clinical features such as the tumor histological variant, the results of post
      ablative whole body scan and the serum thyroglobulin levels. Despite that,
      patients within the same risk group still show a very heterogeneous behavior in
      terms of disease-free interval. As a consequence, the identification of new
      prognostic molecular biomarkers able to testify tumor aggressiveness is highly
      required. Here we'll review recently characterized new molecular markers
      potentially able to ameliorate the prognosis in DTC patients. 

PMID- 24862671
TI  - Double probe intraoperative neuromonitoring with a standardized method in thyroid
      surgery.
AB  - INTRODUCTION: The purpose of this study was to evaluate the effectiveness of
      intraoperative neuromonitoring (IONM) of the recurrent laryngeal nerve (RLN) and
      the vagus nerve (VN) with a standardized approach in thyroid surgery. METHODS:
      Retrospective study with an experimental group with which IONM was used, both
      with the RLN that the VN, and a control one, each consisting of 300 total
      thyroidectomies. Each patient underwent a pre-and post-operative
      videolaryngoscopy. The number of RLNs identified and the number of transient and
      permanent RNL injuries for each group were assessed, and then compared with
      chi(2) tests. In the experimental group Sensitivity, Specificity, Positive
      Predictability, Negative Predictability and Accuracy of IONM were evaluated,
      depending on the number of true positive results, false negatives, true negatives
      and false positives obtained by comparing the results of IONM with the post
      operative videolaryngoscopies. RESULTS: The results obtained for the experimental
      group vs. the control group were: RLNs identified 595 (99.1%) vs. 552 (92%) -P
      Value <0.0001; Permanent RLNs injuries 4 (1.33%) vs. 5 (1.67%) -P Value 1;
      transient RLNs injuries 1 (0.33%) vs. 8 (2.67%) -P Value 0.044. The IONM system,
      for the RLN and VN showed respectively: Sensitivity 66.7% vs. 83.3%; specificity
      97.6% vs. 99.5%; Positive Predictability 22.2% vs. 62.5%; Negative Predictability
      99.6% vs. 99.3%; Accuracy 97.3% vs. 99.3%. CONCLUSIONS: Our study highlights that
      using IONM with a standardized method in thyroid surgery, improves the ability to
      identify the RLN and a reduction in the incidence rate of transient RLN injuries.

PMID- 24862672
TI  - Laparoscopic spleen-preserving distal pancreatectomy for insulinoma: experience
      of a single center.
AB  - BACKGROUND: Laparoscopic spleen-preserving distal pancreatectomy is gaining
      acceptance for the treatment of insulinomas of the pancreatic body and tail. The
      aim of this report is to evaluate the feasibility, safety and outcomes of this
      procedure in a retrospective series. METHODS: From May 2004 to November 2013, 9
      patients underwent laparoscopic spleen-preserving distal pancreatectomy for
      benign insulinomas in our department. Tumors were single and sporadic in eight
      patients, while the remaining patient had insulinomas in the setting of multiple
      endocrine neoplasia type 1. Tumors were located by preoperative imaging in all
      cases. Laparoscopic ultrasound was always performed to guide the surgical
      procedure. RESULTS: All the operations were carried out laparoscopically with a
      mean operative time of 110 min (range 90-210 min) and a mean blood loss of 50 ml
      (range 30-120 ml). One patient (11.1%) died on the 22nd post-operative day for
      massive intra-abdominal bleeding associated with pancreatitis of the stump. Two
      patients (22.2%) developed pancreatic fistula that healed conservatively. Mean
      postoperative hospital stay was 7.1 days (range 5-18 days). All alive patients
      were free from recurrence after a mean follow-up of 45 months (range 11-72
      months). CONCLUSION: Laparoscopic spleen-preserving distal pancreatectomy is safe
      and feasible for the management of benign insulinomas. Definition of the tumor
      with preoperative imaging and laparoscopic ultrasound is essential to achieve
      high cure rate with minimal conversion.

PMID- 24862673
TI  - Does helicobacter pylori infection have influence on outcome of laparoscopic
      sleeve gastrectomy for morbid obesity?
AB  - INTRODUCTION: Among the surgical procedures for treatment of morbid obesity,
      laparoscopic sleeve gastrectomy has known widespread diffusion in the last years,
      although it is not free from significant morbidity rates. Aim of this work is to
      evaluate the incidence of Helicobacter pylori (HP) infection on the postoperative
      outcome of patients undergoing laparoscopic sleeve gastrectomy. METHODS: Between
      January 2008 and December 2013, 184 patients (65 males, 119 females), mean age
      35.8 +/- 5.7 years, affected with morbid obesity, mean BMI 46.6 +/- 6.7,
      underwent laparoscopic sleeve gastrectomy. All the specimens at the end of the
      operation were analysed by the same pathologist. Histological grading was based
      on the Sidney classification. RESULTS: Seventy-two of the patients (39.1%) were
      HP positive, while 112 (60.9%) were negative. No significant differences were
      observed between the HP+ and HP- group in terms of age, sex, weight, BMI,
      incidence of comorbidities and duration of follow-up. All the operations were
      completed via laparoscopic approach. No mortality was observed. Postoperative
      complications occurred in 5 patients (2.7%): three leaks (1.6%), all in the HP-
      group and two bleedings (1.1%), one in the HP+ and one in the HP- group. In two
      cases a reintervention was necessary. No significant differences were observed in
      the morbidity rates between the two groups. Overall mean excess weight loss at 6
      months, 12 months and 24 months was respectively 47.4 +/- 11.3%, 61.1 +/- 12.4%
      and 68.4 +/- 13.5%, with no significant differences between the HP+ and HP-
      groups. CONCLUSIONS: HP infection seems not to influence postoperative outcome of
      patients operated of laparoscopic sleeve gastrectomy.

PMID- 24862674
TI  - The safety of the Harmonic(r) FOCUS in open thyroidectomy: a prospective,
      randomized study comparing the Harmonic(r) FOCUS and traditional suture ligation
      (knot and tie) technique.
AB  - Since Kocher and Billroth refined an acceptable technique, the thyroidectomy has
      become one of the most frequent procedures in endocrine surgery and bilateral
      total thyroidectomy is performed in the majority of thyroid diseases. This work
      evaluated the use of the Harmonic((r)) FOCUS and traditional suture ligation
      (knot and tie) technique in a prospective, randomized study of open
      thyroidectomy. Eighty two patients were randomized and divided into two similarly
      sized groups: the Harmonic((r)) FOCUS group (F group) and traditional group (T
      group). The use of the harmonic FOCUS shows some statistically significant
      advantages limited to a few intraoperative parameters: surgical time and volume
      of blood loss. The surgical time was significantly shorter in F group than in the
      T group (105 +/- 27 min vs 143 +/- 32 respectively; p < 0.05). Intraoperative
      volume blood loss was significantly more in the T group than in the F group (36
      +/- 23 ml vs. 24 +/- 18; p < 0.05). The postoperative parameters (volume of
      drainage fluid, serum calcium at 12 and 48 h, hypocalcemia, wound complication,
      RLN palsy, postoperative pain and length of hospital stay) showed no statistical
      difference. The Harmonic Focus may provide a cost-effective option only in high
      volume centers where reducing operative time may balance the number of daily
      procedures. 

PMID- 24862676
TI  - WITHDRAWN: Bilateral pheochromocytoma importance of multimodality imaging
      assessment.
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- 24862675
TI  - Clinicopathological pattern of lymph node recurrence of papillary thyroid cancer.
      Implications for surgery.
AB  - INTRODUCTION: Lymph nodal involvement in papillary thyroid cancers is very
      common, but the role of lymph node dissection is still controversial. Surgeons
      are consequently divided between opposed to and in favor of routine central neck
      dissection associated with total thyroidectomy. METHODS: Clinical records of 210
      patients undergoing from January 2000 to December 2006 total thyroidectomy
      without routine lymph node dissection were retrospectively evaluated. One hundred
      and ninety eight patients (94.2%) underwent radioiodine ablation as well,
      followed by Thyroid Stimulating Hormone suppression therapy. In patients with
      loco regional lymph nodal recurrence, central (VI) and ipsilateral (III-IV) lymph
      node dissection was performed. RESULTS: Incidence of permanent hypoparathyroidism
      (iPTH < 10 pg/ml) and permanent vocal fold paralysis were respectively 1.4% and
      1.9%. After an 8-year mean follow-up, the rate of loco regional recurrence was
      4.2%-9/210 patients. In these cases selective lymph node dissection was carried
      out without complications. DISCUSSION: The role of neck dissection in papillary
      thyroid cancer management, is still subject of research and controversial
      regarding routine or therapeutic indications, surgical extension, its impact on
      local recurrence and survival. CONCLUSION: A low loco regional recurrence rate
      may be observed after total thyroidectomy without prophylactic lymph node
      dissection. Lymph nodal recurrences were more frequent in young male patients,
      sometime affected by follicular variant, in each case less than 2 cm. There is a
      general agreement about the extension of therapeutic lymph node dissection, while
      routine central neck dissection is still controversial and may be indicated in
      high risk patients.

PMID- 24862677
TI  - Resection of Carotid Body Tumors reduces arterial blood pressure. An
      underestimated neuroendocrine syndrome.
AB  - INTRODUCTION: Carotid Body Tumors (CBTs) are Paragangliomas (PGLs) located in the
      head and neck region which usually do not cause overt neuroendocrine symptoms and
      hypertension. Matrix Metalloproteinases (MMPs) have shown a strong correlation
      between CBTs and their clinical behavior. Aim of this study is to analyze the
      relationship between changes in arterial blood pressure and metalloproteinases
      levels after surgical resection of CBTs. METHODS: We performed a multicenter
      clinical study on 17 patients with benign and malignant CBTs (5 males; 12
      females). Tumors were completely resected and biopsies, obtained at the time of
      surgery, were lysed for Western blot analysis to determine MMPs levels in
      tissues. An enzyme-linked immune sorbent assay (ELISA) kit was used to determine
      the concentration of MMPs in plasma fluid. Blood pressure values were measured at
      admission and at 10 days after surgery. RESULTS: At the time of the admission,
      blood pressure values were higher in patients with CBTs respect to control
      patients; moreover in patients with malignant CBTs blood pressure values were
      higher (P < 0.01) respect to patients with benign CBTs. 10 days after the
      surgery, we documented a significant decrease (P < 0.01) in blood pressure values
      and in MMPs levels in all patients with CBTs. CONCLUSION: These results suggest
      that, despite the CTBs are considered non-functional tumors, an "underestimated"
      neuroendocrine activity on arterial blood pressure may be detected.

PMID- 24862678
TI  - Conventional ultrasound integrated with elastosonography and B-flow imaging in
      the diagnosis of thyroid nodular lesions.
AB  - The purpose of this study was to evaluate the sonographic features of thyroid
      nodules suspicious for malignancy with standard examination in B-mode and Color
      Doppler associated with modern techniques such as ultrasound RTE (Real Time
      Elastosonography) and BFI (B-flow imaging) in correlation with the results of the
      sonographically guided fine-needle aspiration to establish their role in
      predicting the risk of malignancy. Between November 2012 and January 2014, 354
      consecutive patients (age range, 18-73 years; mean age +/- SD, 41.2 +/- 9.2
      years; 90 male and 264 female) with 493 suspected nodules (maximum diameter > 9
      mm) were enrolled in this prospective study. Sonographic, elastosonographic and
      BFI examinations were performed with a commercially available real-time
      ultrasound system, and all patients also underwent a cytologic evaluation.
      Patients with suspicious or malignant cytologic features underwent surgery. On
      histologic examination, 71 of 493 nodules were malignant (62 papillary thyroid
      carcinoma, 1 Hurthle cell carcinoma, and 8 follicular carcinoma). All sonographic
      characteristics, which were potential predictors of thyroid malignancy
      (microcalcifications, hypoechogenicity, absence of a halo, and a predominantly
      solid composition), were found in different percentages in both histologically
      verified malignant and benign nodules. For BFI, pattern 3 (>=4 signs and distance
      > 2 mm) was the most predictive factor for malignancy (specificity, 99.6%;
      sensitivity, 65.2%), whereas pattern 2 (>=4 signs and distance < 2 mm) was a
      positive factor because it was detected only in benign lesions. For the RTE,
      scores 1-2 were detected in 68% of benign nodules, while scores 3-4 in 94% of
      malignant nodules. Our results indicate that Elastosonography and BFI can
      overcome the limits of the traditional B-mode and color Doppler sonographic
      features in the diagnosis of thyroid nodules. This techniques provides maximum
      specificity levels both in the case of benign nodules and in the case of
      malignant nodules. 

PMID- 24862679
TI  - Social support from church and family members and depressive symptoms among older
      African Americans.
AB  - OBJECTIVE: This study examined the influence of church- and family-based social
      support on depressive symptoms and serious psychological distress among older
      African Americans. METHODS: The analysis is based on the National Survey of
      American Life. Church- and family-based informal social support correlates of
      depressive symptoms (CES-D) and serious psychological distress (K6) were
      examined. Data from 686 African Americans aged 55 years or older who attend
      religious services at least a few times a year are used in this analysis.
      RESULTS: Multivariate analysis found that social support from church members was
      significantly and inversely associated with depressive symptoms and psychological
      distress. Frequency of negative interactions with church members was positively
      associated with depressive symptoms and psychological distress. Social support
      from church members remained significant but negative interaction from church
      members did not remain significant when controlling for indicators of family
      social support. Among this sample of churchgoers, emotional support from family
      was a protective factor and negative interaction with family was a risk factor
      for depressive symptoms and psychological distress. CONCLUSION: This is the first
      investigation of the relationship between church- and family-based social support
      and depressive symptoms and psychological distress among a national sample of
      older African Americans. Overall, the findings indicate that social support from
      church networks was protective against depressive symptoms and psychological
      distress. This finding remained significant when controlling for indicators of
      family social support.

PMID- 24862681
TI  - Thyroid metastasis of a colonic adenocarcinoma.

PMID- 24862680
TI  - Alcohol consumption patterns and cognitive impairment in older women.
AB  - OBJECTIVE: Few studies have investigated changes in alcohol consumption and risk
      of cognitive impairment among oldest old adults. METHODS: In a prospective study
      of 1309 women >=65 years old, alcohol use was assessed at repeated visits and
      used to estimate average change in alcohol consumption over 16 years. Clinically
      significant cognitive impairment (mild cognitive impairment and dementia) was
      assessed at year 20. RESULTS: Compared with the reference group (slight decrease
      in alcohol consumption by 0-0.5 drinks/week, 60.4%), increasing consumption over
      time (>0 drinks/week) was not associated with risk of cognitive impairment (5.0%,
      odds ratio [OR]: 1.00, 95% confidence interval [CI]: 0.54-1.85). Decreasing
      consumption by >0.5 drinks/week was associated with increased risk (34.5%, OR:
      1.34, 95% CI: 1.05-1.70). Adjustment for age, education, diabetes, smoking, BMI,
      and physical activity attenuated the magnitude of the effect slightly and
      resulted in borderline statistical significance. CONCLUSION: Women in their ninth
      and tenth decade of life who decrease alcohol use may be at risk of cognitive
      impairment.

PMID- 24862682
TI  - Obstructive cecal cancer in a centennial patient: Surgical management.

PMID- 24862683
TI  - Intestinal obstruction caused by an incarcerated diaphragmatic hernia after an
      Ivor-Lewis procedure.

PMID- 24862684
TI  - Predictive factors for mortality in Fournier' gangrene: a series of 59 cases.
AB  - AIMS: Fournier's gangrene (FG) is the necrotizing fasciitis of the perineum and
      genital area and presents a high mortality rate. The aim was to assess prognostic
      factors for mortality, create a new mortality predictive scale and compare it
      with previously published scales in patients diagnosed with FG in our Emergency
      Department. METHODS: Retrospective analysis study between 1998 and 2012. RESULTS:
      Of the 59 patients, 44 survived (74%) (S) and 15 died (26%) (D). Significant
      differences were found in peripheral vasculopathy (S 5 [11%]; D 6 [40%]; P=.023),
      hemoglobin (S 13; D 11; P=.014), hematocrit (S 37; D 31.4; P=.009), white blood
      cells (S 17,400; D 23,800; P=.023), serum urea (S 58; D 102; P<.001), creatinine
      (S 1.1; D 1.9; P=.032), potassium (S 3.7; D 4.4; P=.012) and alkaline phosphatase
      (S 92; D 133; P=.014). Predictive scores: Charlson index (S 1; D 4; P=.013),
      severe sepsis criteria (S 16 [36%]; D 13 [86%]; P=.001), Fournier's gangrene
      severity index score (FGSIS) (S 4; D 7; P=.002) and Uludag Fournier's Gangrene
      Severity Index (UFGSI) (S 9; D 13; P=.004). Independent predictive factors were
      peripheral vasculopathy, serum potassium and severe sepsis criteria, and a model
      was created with an area under the ROC curve of 0.850 (0.760-0.973), higher than
      FGSIS (0.746 [0.601-0.981]) and UFGSI (0.760 [0.617-0.904]). CONCLUSIONS: FG
      showed a high mortality rate. Independent predictive factors were peripheral
      vasculopathy, potassium and severe sepsis criteria creating a predictive model
      that performed better than those previously described.

PMID- 24862685
TI  - Lithopedion.

PMID- 24862686
TI  - Solid-state biophotovoltaic cells containing photosystem I.
AB  - The large multiprotein complex, photosystem I (PSI), which is at the heart of
      light-dependent reactions in photosynthesis, is integrated as the active
      component in a solid-state organic photovoltaic cell. These experiments
      demonstrate that photoactive megadalton protein complexes are compatible with
      solution processing of organic-semiconductor materials and operate in a dry non
      natural environment that is very different from the biological membrane. 

PMID- 24862687
TI  - Unnaturalised racial naturalism.
AB  - Quayshawn Spencer (2014) misunderstands my treatment of racial naturalism. I
      argued that racial naturalism must entail a strong claim, such as "races are
      subspecies", if it is to be a substantive position that contrasts with anti
      realism about biological race. My recognition that not all race naturalists make
      such a strong claim is evident throughout the article Spencer reviews (Hochman,
      2013a). Spencer seems to agree with me that there are no human subspecies, and he
      endorses a weaker form of racial naturalism. However, he supports his preferred
      version of 'racial naturalism' with arguments that are not well described as
      'naturalistic'. I argue that Spencer offers us an unnaturalised racial
      naturalism.

PMID- 24862688
TI  - Ecotoxicological studies of micro- and nanosized barium titanate on aquatic
      photosynthetic microorganisms.
AB  - The interaction between live organisms and micro- or nanosized materials has
      become a current focus in toxicology. As nanosized barium titanate has gained
      momentum lately in the medical field, the aims of the present work are: (i) to
      assess BT toxicity and its mechanisms on the aquatic environment, using two
      photosynthetic organisms (Anabaena flos-aquae, a colonial cyanobacteria, and
      Euglena gracilis, a flagellated euglenoid); (ii) to study and correlate the
      physicochemical properties of BT with its toxic profile; (iii) to compare the BT
      behavior (and Ba(2+) released ions) and the toxic profile in synthetic (Bold's
      Basal, BB, or Mineral Medium, MM) and natural culture media (Seine River Water,
      SRW); and (iv) to address whether size (micro, BT MP, or nano, BT NP) is an issue
      in BT particles toxicity. Responses such as growth inhibition, cell viability,
      superoxide dismutase (SOD) activity, adenosine-5-triphosphate (ATP) content and
      photosynthetic efficiency were evaluated. The main conclusions are: (i) BT have
      statistically significant toxic effects on E. gracilis growth and viability even
      in small concentrations (1MUgmL(-1)), for both media and since the first 24 h; on
      the contrary of on A. flos-aquae, to whom the effects were noticeable only for
      the higher concentrations (after 96 h: >=75 MUg mL(-1) for BT NP and =100 MUg mL(
      1) for BT MP, in BB; and >=75 MUg mL(-1) for both materials in SRW), in spite of
      the viability being affected in all concentrations; (ii) the BT behaviors in
      synthetic and natural culture media were slightly different, being the toxic
      effects more pronounced when grown in SRW - in this case, a worse physiological
      state of the organisms in SRW can occur and account for the lower resistance,
      probably linked to a paucity of nutrients or even a synergistic effect with a
      contaminant from the river; and (iii) the effects seem to be mediated by induced
      stress without a direct contact in A. flos-aquae and by direct endocytosis in E.
      gracilis, but in both organisms the contact with both BT MP and BT NP increased
      SOD activity and decreased photosynthetic efficiency and intracellular ATP
      content; and (iv) size does not seem to be an issue in BT particles toxicity
      since micro- and nano-particles produced significant toxic for the model
      organisms.

PMID- 24862689
TI  - Histological and molecular-biological analyses of poly(3-hydroxybutyrate) (PHB)
      patches for enhancement of bone regeneration.
AB  - Tissue engineered cell-seeded constructs with poly(3)hydroxybutyrate (PHB)
      induced ectopic bone formation after implantation into the back muscle of rats.
      The objective of our in vivo study was to evaluate the osteogenic potential of
      pure PHB patches in surgically created cranial defects. For this, PHB patches
      were analyzed after implantation in surgically created defects on the cranium of
      adult male rats. After healing periods of 4, 8 and 12 weeks, the bone tissue
      specimens containing PHB patches were processed and analyzed histologically as
      well as molecular-biologically. After 4 weeks, the PHB patches were completely
      embedded in connective tissue. Eight weeks after PHB insertion, bone regeneration
      proceeding from bearing bone was found in 50% of all treated animals, whereas all
      PHB treated cavities showed both bone formation and embedding of the patches in
      bone 12 weeks after surgery. Furthermore, all slices showed pronounced
      development of blood vessels. Histomorphometric analysis presented a regenerated
      bone mean value between 46.4 +/- 16.1% and 54.2 +/- 19.3% after 4-12 weeks of
      healing. Caveolin-1 staining in capillary-like structures showed a 1.16-1.38 fold
      increased expression in PHB treated defects compared to controls. Real-time RT
      PCR analyses showed significantly lower expressions of Alpl, Col1a1 and VEGFA in
      cranium defects after treatment with PHB patches compared to untreated bony
      defects of the same cranium. Within the limits of the presented animal
      investigation, it could conclude that the tested PHB patches featured a good
      biocompatibility and an osteoconductive character.

PMID- 24862691
TI  - Juvenile megaesophagus in PKCalpha-deficient mice is associated with an increase
      in the segment of the distal esophagus lined by smooth muscle cells.
AB  - Megaesophagus in mice has been associated with several genetic defects. In the
      present study we expand the range of genes associated with esophageal function
      and morphology by protein kinase C alpha (PKCalpha). PKCalpha-deficient mice
      showed a six times increased prevalence of megaesophagus at the age of 9-10 weeks
      compared to wild-type animals. In contrast, in a restricted number of 14-month
      old animals of both genotypes a similar prevalence of megaesophagus was found.
      Megaesophagus was associated with an increased portion of the distal esophagus
      lined by smooth muscle cells. Achalasia-like degeneration or loss of neuronal
      cells, inflammation or fibrosis was not present in any of the animals. The
      results of the study therefore suggest that PKCalpha expression is associated
      with a delayed replacement of embryonic smooth muscle by skeletal muscle at the
      distal esophagus and consecutive megaesophagus in young mice, which, however, is
      not present at the same prevalence at an advanced age. 

PMID- 24862693
TI  - Could the New England Journal of Medicine be biased against arthroscopic knee
      surgery? Part 2.

PMID- 24862694
TI  - AAOS Osteoarthritis Guideline: transparency and credibility.

PMID- 24862695
TI  - Authors' reply.

PMID- 24862696
TI  - New England journal of medicine article evaluating the usefulness of meniscectomy
      is flawed.

PMID- 24862697
TI  - Authors' reply.

PMID- 24862698
TI  - Tibial insertion is not a circle but an ellipse.

PMID- 24862699
TI  - Arthroscopic subscapularis repair: a look at primacy from a historical
      perspective.

PMID- 24862700
TI  - Chronic overcirculation-induced pulmonary arterial hypertension in aorto-caval
      shunt.
AB  - Pulmonary arterial hypertension is a common complication of congenital heart
      defects with left-to-right shunts. Current preclinical models do not reproduce
      clinical characteristics of shunt-related pulmonary hypertension. Aorto-caval
      shunt was firstly described as a model of right ventricle volume overload. The
      pathophysiology and the possible determination of pulmonary arterial hypertension
      of different periods of shunt exposure are still undefined. A method to create
      standardized, reproducible aorto-caval shunt was developed in growing rats (260+/
      40 g). Three groups of animals were considered: shunt exposure for 10 weeks,
      shunt exposure for 20 weeks and control (sham laparotomy). Echocardiography and
      magnetic resonance revealed increased right ventricular end diastolic area in
      shunt at 10 weeks compared to control. Hemodynamic analysis demonstrated
      increased right ventricular afterload and increased effective pulmonary arterial
      elastance (Ea) in shunt at 20 weeks compared to control (1.29+/-0.20 vs. 0.14+/
      0.06 mmHg/MUl, p=0.004). At the same time point, the maximal slope of end
      systolic pressure-volume relationship (Ees) decreased (0.5+/-0.2 mmHg/ml vs.
      1.2+/-0.3, p<0.001). Consequently, right ventricular-arterial coupling was
      markedly deteriorated with a ~50% decrease in the ratio of end-systolic to
      pulmonary artery elastance (Ees/Ea). Finally, left ventricular preload diminished
      (~30% decrease in left ventricular end-diastolic volume). Histology demonstrated
      medial hypertrophy and small artery luminal narrowing. Chronic exposure to aorto
      caval shunt is a reliable model to produce right ventricular volume overload and
      secondary pulmonary arterial hypertension. This model could be an alternative
      with low mortality and high reproducibility for investigators on the underlying
      mechanisms of shunt-related pulmonary hypertension.

PMID- 24862701
TI  - Efficacy of articaine versus lidocaine as a supplemental buccal infiltration in
      mandibular molars with irreversible pulpitis: a prospective, randomized, double
      blind study.
AB  - INTRODUCTION: Profound pulpal anesthesia in mandibular molars with irreversible
      pulpitis (IP) is often difficult to obtain and often requires supplemental
      injections after an ineffective inferior alveolar nerve block (IANB). The purpose
      of this prospective, randomized, double-blind study was to compare the efficacy
      of 4% articaine with 2% lidocaine for supplemental buccal infiltrations (BIs)
      after an ineffective IANB in mandibular molars with IP. In addition, the use of
      articaine for IANB and intraosseous injections was investigated. METHODS: One
      hundred emergency patients diagnosed with IP of a mandibular molar were selected
      and received an IANB with 4% articaine. All injections were 1.7 mL with 1:100,000
      epinephrine. All patients reported profound lip numbness after IANB. Patients
      with ineffective IANB (positive pulpal response to cold or pain on access)
      randomly received 4% articaine or 2% lidocaine as a supplemental BI. Endodontic
      access was initiated 5 minutes after deposition of the infiltration solution.
      Success was defined as no pain or no more than mild pain during endodontic access
      and instrumentation as measured on a visual analogue scale. RESULTS: Seventy-four
      patients failed to achieve pulpal anesthesia after IANB with 4% articaine,
      resulting in IANB success rate of 26%. Success rates for supplemental BIs were
      62% for articaine and 37% for lidocaine (P < .05). This effect was most
      pronounced in second molars (P < .05). CONCLUSIONS: Supplemental BI with
      articaine was significantly more effective than lidocaine. The IANB success rate
      of 4% articaine confirmed published data.

PMID- 24862702
TI  - Clinical efficacy of electronic apex locators: systematic review.
AB  - INTRODUCTION: Apical constriction has been proposed as the most appropriate
      apical limit for the endodontic working length. Despite being the most used, some
      limitations are attributed to the radiographic method of working length
      determination. It lacks precision because it is based on the average position of
      the apical constriction. The electronic apex locators have been presented as an
      alternative to the odontometry performed by radiography. These devices detect the
      transition of the pulp to the periodontal tissue, which is anatomically very
      close to the apical constriction and may perform with improved accuracy. METHODS:
      A systematic review was performed to compare the radiographic and electronic
      methods. Clinical studies that compared both methods were searched for on 7
      electronic databases, a manual search was performed on the bibliography of
      articles collected on the electronic databases, and the authors were contacted to
      ask for references of more research not detected on the electronic and manual
      search. RESULTS: Twenty-one articles were selected. The majority were comparative
      or evaluation studies, and very few clinical studies comparing both methods are
      available. Several methodological limitations are present on the collected
      articles and debated in this review. CONCLUSIONS: Although the available
      scientific evidence base is short and at considerable risk of bias, it is still
      possible to conclude that the apical locator reduces the patient radiation
      exposure and also that the electronic method may perform better on the working
      length determination. At least one radiographic control should be performed to
      detect possible errors of the electronic devices.

PMID- 24862703
TI  - Microbial evaluation of traumatized teeth treated with triple antibiotic paste or
      calcium hydroxide with 2% chlorhexidine gel in pulp revascularization.
AB  - INTRODUCTION: Revascularization outcome depends on microbial elimination because
      apical repair will not happen in the presence of infected tissues. This study
      evaluated the microbial composition of traumatized immature teeth and assessed
      their reduction during different stages of the revascularization procedures
      performed with 2 intracanal medicaments. METHODS: Fifteen patients (7-17 years
      old) with immature teeth were submitted to the revascularization procedures; they
      were divided into 2 groups according to the intracanal medicament used: TAP group
      (n = 7), medicated with a triple antibiotic paste, and CHP group (n = 8), dressed
      with calcium hydroxide + 2% chlorhexidine gel. Samples were taken before any
      treatment (S1), after irrigation with 6% NaOCl (S2), after irrigation with 2%
      chlorhexidine (S3), after intracanal dressing (S4), and after 17% EDTA irrigation
      (S5). Cultivable bacteria recovered from the 5 stages were counted and identified
      by means of polymerase chain reaction assay (16S rRNA). RESULTS: Both groups had
      colony-forming unit counts significantly reduced after S2 (P < .05); however, no
      significant difference was found between the irrigants (S2 and S3, P = .99). No
      difference in bacteria counts was found between the intracanal medicaments used
      (P = .95). The most prevalent bacteria detected were Actinomyces naeslundii
      (66.67%), followed by Porphyromonas endodontalis, Parvimonas micra, and
      Fusobacterium nucleatum, which were detected in 33.34% of the root canals. An
      average of 2.13 species per canal was found, and no statistical correlation was
      observed between bacterial species and clinical/radiographic features.
      CONCLUSIONS: The microbial profile of infected immature teeth is similar to that
      of primarily infected permanent teeth. The greatest bacterial reduction was
      promoted by the irrigation solutions. The revascularization protocols that used
      the tested intracanal medicaments were efficient in reducing viable bacteria in
      necrotic immature teeth.

PMID- 24862704
TI  - Clinical decision making for a tooth with apical periodontitis: the patients'
      preferred level of participation.
AB  - INTRODUCTION: To effectively engage patients in clinical decisions regarding the
      management of teeth with apical periodontitis (AP), there is a need to explore
      patients' perspectives on the decision-making process. This study surveyed
      patients for their preferred level of participation in making treatment decisions
      for a tooth with AP. METHODS: Data were collected through a mail-out survey of
      800 University of Toronto Faculty of Dentistry patients, complemented by a
      convenience sample of 200 patients from 10 community practices. The Control
      Preferences Scale was used to evaluate the patients' preferences for active,
      collaborative, or passive participation in treatment decisions for a tooth with
      AP. Using bivariate and logistic regression analyses, the Gelberg-Andersen
      Behavioral Model for Vulnerable Populations was applied to the Control
      Preferences Scale questions to understand the influential factors (P <= .05).
      RESULTS: Among 434 of 1,000 respondents, 44%, 40%, and 16% preferred an active,
      collaborative, and passive participation, respectively. Logistic regression
      showed a significant association (P <= .025) between participants' higher
      education and preference for active participation compared with a collaborative
      role. Also, immigrant status was significantly associated with preference for
      passive participation (P = .025). CONCLUSIONS: The majority of patients valued an
      active or collaborative participation in deciding treatment for a tooth with AP.
      This pattern implied a preference for a patient-centered practice mode that
      emphasizes patient autonomy in decision making.

PMID- 24862705
TI  - Treatment outcome of mineral trioxide aggregate: repair of root perforations-long
      term results.
AB  - INTRODUCTION: This historical cohort study follows on a previously reported
      trial, with the aim of assessing the outcome for teeth with root perforations
      managed by the orthograde placement of mineral trioxide aggregate (MTA) and
      identifying potential outcome factors for such treatment with a larger sample
      size and longer follow-up periods than in the first phase of the project.
      METHODS: The treatment outcomes of 64 root perforations repaired between 2000 and
      2012 with MTA were investigated. The root perforations were located in different
      areas of the root. Calibrated examiners assessed clinical and radiographic
      outcomes by using standardized follow-up protocols 12-107 months after treatment
      (median, 27.5 months). Preoperative, intraoperative, and postoperative
      information was evaluated. The outcomes were dichotomized as healed or diseased.
      RESULTS: Of the 64 teeth examined (85% recall rate), 86% were healed. The
      univariate analyses (chi(2) tests) identified 2 potential prognostic factors,
      experience of the treatment providers (odds ratio, 2.14; 95% confidence interval,
      0.39-11.74; P < .01) and placement of a post after treatment (odds ratio, 0.06;
      95% confidence interval, 0.01-0.27; P < .01). In the multivariate stepwise
      logistic Cox regression, none of the potential prognostic factors displayed a
      significant effect on the outcome at the 5% level. CONCLUSIONS: MTA appears to
      have good long-term sealing ability for root perforations regardless of the
      location. The results of this historical cohort study confirm the results of the
      first phase of this project.

PMID- 24862706
TI  - Applicant selection procedures in endodontic specialty programs in the United
      States: program director's perspective.
AB  - INTRODUCTION: The purpose of this study was to determine the criteria evaluated
      by directors of endodontic specialty programs in the United States when selecting
      their residents and their satisfaction with the current process. Besides this,
      the study also aimed to determine the expected effect of the change in National
      Board Dental Examination (NBDE) score reporting to pass/fail on applicant
      evaluation. METHODS: A 38-question web-based survey was distributed to the 54
      endodontic specialty program directors (of 55 programs) in the United States.
      Questions regarded general program information, information obtained from
      applications, the interview process, the decision process, a retrospective view
      of the selection process, and director demographics. RESULTS: Twenty-six (48.1%)
      responses were returned and analyzed. The most important application factors were
      interview ratings, dental school class rank, and general practice residency or
      advanced education in general dentistry experience. The most preferred sources
      for letters of recommendation were endodontic pre- and postdoctoral program
      directors and other academic endodontists. Desirable applicant characteristics
      included enthusiasm, listening skills, and verbal skills. Program directors
      indicated concern regarding the initial screening of applicants after the NBDE
      scoring change but not as much concern relating to final selection. Respondents
      generally supported a uniform acceptance date but did not support participation
      in the Postdoctoral Dental Matching Program (the Match). CONCLUSIONS: Some
      important criteria when selecting prospective residents were identified. Program
      directors did not appear overwhelmingly concerned with the changes in NBDE score
      reporting. In addition, the establishment of a uniform acceptance date may
      resolve the biggest problem most respondents have with the current selection
      process.

PMID- 24862707
TI  - Improvement in oral health-related quality of life after endodontic treatment: a
      prospective longitudinal study.
AB  - INTRODUCTION: To date, evidence of the effectiveness of endodontic treatment and
      criteria of success have mainly been considered in terms of clinical outcome, and
      there is a lack of information of treatment outcomes from patients' perspectives.
      This study aimed to assess changes in quality of life after endodontic treatment
      and to determine if changes in quality of life were associated with changes in
      patient-perceived oral health and clinical assessments of success. METHODS: This
      longitudinal study involved 279 subjects. Patient-reported outcome measures based
      on oral health-related quality of life was assessed using the short form of the
      Oral Health Impact Profile (OHIP-14). The patients completed the assessments
      before endodontic treatment and 1 month and 6 months after root canal obturation.
      A global oral health transition assessment was ascertained by a single (global)
      item rating of oral health improvement and clinical assessment mainly based on
      the Periapical Index (PAI) of periapical radiographs. RESULTS: There were
      significant changes in OHIP-14 scores over the study period after conventional
      orthograde endodontic treatment (from pretreatment-6 months postobturation) (P <
      .001). The magnitude of statistical change (effect size) was moderate (0.61) in
      the short-term (after 1 month) and large (0.71) in the longer-term (after 6
      months). Changes in the OHIP-14 was associated with changes in patient self
      rating oral health status (P < .001), which was also associated with changes in
      PAI scores (P < .05). CONCLUSIONS: Endodontic treatment improves quality of life.
      The OHIP-14 measure is both sensitive and responsive to endodontic treatment and
      is likely to be useful in understanding patients' perspectives of outcomes from
      endodontic care.

PMID- 24862708
TI  - Effect of EDTA on attachment and differentiation of dental pulp stem cells.
AB  - INTRODUCTION: In regenerative endodontics, it is believed that EDTA induces
      odontoblast differentiation by releasing growth factors from the dentin matrix.
      The aim of this study was to evaluate the effect of EDTA on the attachment and
      differentiation of dental pulp stem cells (DPSCs). We also investigated whether
      the behavioral changes of DPSCs could be caused by biochemical components
      released from EDTA-treated dentin. METHODS: Cells were obtained from human third
      molars, and the stem-like nature of the cells was investigated by flow cytometric
      analysis. DPSCs were seeded on EDTA-treated and untreated dentin slices. After 3
      days of culture, cell attachment was evaluated by cell density, fibronectin 1
      gene expression level using quantitative real-time polymerase chain reaction, and
      scanning electron microscopy. After 21 days of culture, the expression of
      differentiation genes was investigated by quantitative real-time polymerase chain
      reaction, and calcification was observed using alizarin red S staining. To
      investigate the EDTA-induced growth factor release, DPSCs were cultured with or
      without direct contact with the EDTA-treated dentin surface. RESULTS: After 3
      days of culture, both the cell density and fibronectin expression level were
      significantly higher in the EDTA-treated dentin group. After 3 weeks, the DPSCs
      on the EDTA-treated dentin surfaces showed higher expression levels of dentin
      sialophosphoprotein and dentin matrix protein 1, whereas the DPSCs cultured
      without direct contact with the EDTA-treated dentin surfaces did not exhibit
      these findings. CONCLUSIONS: Our results showed that EDTA induced cell attachment
      and odontoblastic/osteoblastic differentiation, which was observed only in the
      group in which the DPSCs were placed in direct contact with the EDTA-treated
      dentin surfaces. These findings suggest that EDTA is beneficial for achieving
      successful outcomes in regenerative endodontics.

PMID- 24862709
TI  - Role of the P38 pathway in calcium silicate cement-induced cell viability and
      angiogenesis-related proteins of human dental pulp cell in vitro.
AB  - INTRODUCTION: This study investigated that calcium silicate (CS) cement may
      influence the behavior of human dental pulp cells (hDPCs) via mitogen-activated
      protein kinase pathway, in particular p38. We have addressed that Si ion released
      from CS cement can influence osmolarity in the medium, which may stimulate hDPC
      viability and induce angiogenesis-related proteins through stimulation of the
      nitric oxide synthase and nitric oxide secretion. METHODS: The hDPCs was cultured
      with CS cement to angiogenesis. Then, cell viability, ion concentration,
      osmolality, nitric oxide secretion, the von Willebrand factor, and angiopoietin-1
      protein expression were examined. RESULTS: CS cement elicited a significant (P <
      .05) increase of 15%, 20%, and 19% in viability compared with control on days 1,
      3, and 5 of cell seeding, respectively. The CS cement consumed calcium and
      phosphate ions and released more Si ions in medium. The CS significantly (P <
      .05) increased the osmolality to 303.52 +/- 3.07, 315.03 +/- 5.80, and 319.95 +/-
      4.68 mOsm/kg for 1, 3, and 5 days, respectively. P38 was activated through
      phosphorylation; the phosphorylation kinase was investigated in our cell system
      after culture with CS cement. Moreover, expression levels for angiopoietin-1 and
      von Willebrand factor in hDPCs on CS cement were higher than those of the CS +
      p38 inhibitor (SB203580) group (P < .05) at all of the analyzed time points.
      CONCLUSIONS: This study showed that CS cement was able to activate the p38
      pathway in hDPCs cultured in vitro. Moreover, Si was shown to increase osmolality
      required to facilitate the angiogenic differentiation of hDPCs via the p38
      signaling pathway. When the p38 pathway was blocked by SB203580, the angiogenic
      dependent protein secretion was decreased. These findings verified that the p38
      pathway plays a key role in regulating the angiogenic behavior of hDPCs cultured
      on CS cement.

PMID- 24862710
TI  - Extension of bactericidal effect of sodium hypochlorite into dentinal tubules.
AB  - INTRODUCTION: The aim of this study was to determine the extent of disinfection
      mediated by 2 concentrations of sodium hypochlorite for bacteria-laden dentin
      wall of a root canal. METHODS: A dual-species film, Enterococcus faecalis and
      Porphyromonas gingivalis, was cultivated on root canal dentin for 7 days. The
      canal wall was irrigated with 0.5% or 3% sodium hypochlorite (n = 8 each), with a
      control group (n = 2) irrigated with sterile saline. The roots were then split
      horizontally at 5-, 7-, and 9-mm levels from root apex and examined under
      confocal laser scanning microscope and then scanning electron microscope. The
      proportions of viable cells situated on different depths into root canal dentin
      were compared at a significance level of P = .05. RESULTS: Both concentrations of
      sodium hypochlorite significantly reduced the amount of live bacteria in the most
      superficial layer (first 0.1 mm) of root canal dentin, compared with the control;
      however, the difference was not significant between the 2 concentrations. For the
      next 2 layers (0.1-0.3 mm into dentinal tubules), irrigation with 3% hypochlorite
      resulted in significantly lower amounts of viable bacteria than 0.5% hypochlorite
      or saline. No significant difference between 0.5% or 3% sodium hypochlorite and
      the positive control was observed in deeper (>0.3 mm) regions into the root canal
      wall. CONCLUSIONS: Increasing the concentration of sodium hypochlorite improves
      the penetration depth of its antibacterial action into dentinal tubules, but that
      seemed unable to completely eradicate bacteria residing there. Total elimination
      of bacteria from dentinal tubules cannot be achieved by irrigation with sodium
      hypochlorite alone.

PMID- 24862711
TI  - Expression of heat shock proteins in periapical granulomas.
AB  - INTRODUCTION: Cells from virtually all organisms respond to a variety of stresses
      by the rapid synthesis of a highly conserved set of polypeptides termed heat
      shock proteins (HSPs). HSPs protect cells under adverse conditions such as
      infection, inflammation, and disease. We hypothesize that endodontic infection
      might result in an imbalance in the expression of heat shock genes, accounting
      for different clinical outcomes in periapical lesions. METHODS: We analyzed the
      expression of 44 HSPs genes using a pathway-specific real-time polymerase chain
      reaction array in 93 human periapical granulomas and 24 healthy periodontal
      ligament tissues collected postoperatively. Observed variations in the expression
      of HSP genes were also analyzed based on the classification of periapical
      granulomas as active or inactive. In addition, U937 cells were differentiated
      into macrophages, infected with different concentrations of purified Escherichia
      coli lipopolysaccharide (LPS), and used as templates for the HSP gene array.
      Protein expression was assessed by immunohistochemistry. RESULTS: The expression
      of HSP genes was significantly increased in granulomas compared with healthy
      periodontal ligament (P < .00001). Among the 44 HSP genes, DNAJC3, HSPA4, HSPA6,
      and HSPB1 showed the highest expression levels in both granulomas and LPS-treated
      macrophages. DNAJC3, HSPA6, and HSPB1 were highly expressed in active lesions,
      whereas HSPA4 expression was higher in inactive lesions (P < .005). Higher
      concentrations of LPS led to increased HSP expression in macrophages (P < .0001).
      Immunocytochemistry confirmed the expression and colocalization of HSPB1 and
      HSPA6 proteins in the cytoplasm of LPS-infected macrophages. CONCLUSIONS: The
      observed differential expression patterns of HSPs in periapical granulomas and
      LPS-infected macrophages suggest that HSP genes and proteins are involved in
      periapical lesion development and may account for different clinical outcomes.
      Understanding the role of the heat shock response might provide additional
      insights into the process of periapical lesion development.

PMID- 24862712
TI  - Periapical inflammation subsequent to coronal inoculation of dog teeth root
      filled with resilon/epiphany in 1 or 2 treatment sessions with chlorhexidine
      medication.
AB  - INTRODUCTION: Therapeutic methods that inhibit microbial ingress into filled root
      canals are desirable. This in vivo study assessed the inhibition of periapical
      inflammation subsequent to coronal inoculation in canals medicated with 2%
      chlorhexidine gel and filled with Resilon/Epiphany (Pentron Clinical
      Technologies, Wallingford, CT). METHODS: Six Beagle dogs each had 10 two-rooted
      premolars treated. In group 1 (n = 36 roots), 1 root/tooth had the canal
      conditioned with Primer Epiphany, filled with Epiphany sealer and Resilon core in
      1 session, and coronally sealed with PhotacFil. In group 2 (n = 36 roots), the
      second root/tooth had the canal medicated with 2% chlorhexidine gel for 1 week
      and then filled and coronally sealed as in group 1. After 3 weeks, canals were
      exposed to the oral environment for 7 days, inoculated with isologous plaque, and
      coronally sealed. Negative controls treated as groups 1 and 2 remained sealed.
      Positive controls had canals unfilled and exposed. Seven months after
      inoculation, dogs were euthanized; jaw blocks processed for histologic
      examination; and periapical inflammation (PI) recorded as none, mild, or severe.
      RESULTS: In groups 1 and 2, severe PI occurred in 5 of 65 roots (8%) and mild PI
      in 18 of 65 roots (28%) with a significantly higher (P = .031) PI incidence in
      group 2 than in group 1. Negative controls had only mild PI in 9 of 29 roots
      (31%). Roots medicated with 2% chlorhexidine gel had mild PI significantly more
      (P = .009) than roots filled in 1 session (more than 2-fold). CONCLUSIONS:
      Intracanal medication with 2% chlorhexidine gel and root filling with
      Resilon/Epiphany did not effectively inhibit apical periodontitis subsequent to
      coronal inoculation.

PMID- 24862713
TI  - Investigation of dentin hardness in roots exhibiting the butterfly effect.
AB  - INTRODUCTION: Most vertical root fractures occur in root canal treated teeth, and
      they usually run in a buccolingual direction. The butterfly effect is an optical
      phenomenon seen in some sections of tooth roots. The aim was to investigate the
      microhardness of dentin in mesiodistal and buccolingual cross sections of roots
      exhibiting the effect. METHODS: Thirty extracted single-rooted teeth were
      allocated according to patient age: group 1, 15-24 years; group 2, 25-44 years;
      and group 3, 45 years and older. Roots were embedded in acrylic and cut into ten
      1-mm-thick cross sections. Sections were viewed under a light microscope and
      coded (1 or 2) according to presence or absence of the butterfly effect. A root
      scored 20 when all levels featured the butterfly appearance. The 2 teeth with the
      highest score from each group and 2 control teeth with the minimum score (10)
      were selected. Two adjacent, consecutive cross sections were chosen from the
      middle of the roots. Vickers microhardness testing was carried out on the dentin
      walls. RESULTS: Mean hardness scores were highest mesiodistally (83.7 kgf/mm(2))
      and lowest buccolingually (56.4 kgf/mm(2)), a significant difference (P = .028).
      This trend was found across all age groups. CONCLUSIONS: Root sections with the
      butterfly effect are harder mesiodistally. This might explain the high prevalence
      of vertical root fractures that run buccolingually.

PMID- 24862714
TI  - Spectrophotometric analysis of crown discoloration induced by various antibiotic
      pastes used in revascularization.
AB  - INTRODUCTION: Antibiotic pastes are used for disinfection in regenerative
      endodontic procedures. This study evaluated the crown discoloration induced by
      various antibiotic pastes including the mixture of metronidazole and
      ciprofloxacin with minocycline, doxycycline, amoxicillin, or cefaclor. METHODS:
      Seventy extracted bovine incisors were sectioned to obtain a standardized root
      length of 10 mm above the facial cementoenamel junction. After pulp tissue
      removal, irrigation with sodium hypochlorite and the placement of temporary
      filling material and cotton pellet were performed from the apical aspect. The
      specimens were then randomly divided into 7 groups (n = 10 for each group), and
      each group received the following antibiotic paste fillings: no filling (control
      group), calcium hydroxide, double antibiotic paste (DAP), triple antibiotic paste
      (TAP) with minocycline, TAP with doxycycline, TAP with amoxicillin, and TAP with
      cefaclor. Spectrophotometric readings were obtained on the buccal surfaces of the
      crown on day 1 to week 3 after filling, and the DeltaE value was calculated. Data
      were analyzed with 2-way analysis of variance and the Tukey post hoc tests (P =
      .05), and the human perceptibility threshold was set to 3.7. RESULTS: TAP with
      minocycline, doxycycline, and cefaclor induced more coronal discoloration
      compared with the control group (P < .05). The control, calcium hydroxide, and
      DAP groups showed no color changes exceeding the perceptibility threshold at all
      time points. CONCLUSIONS: The results indicated that all antibiotic pastes,
      except DAP, induced crown discoloration.

PMID- 24862715
TI  - Dentinal damage and fracture resistance of oval roots prepared with single-file
      systems using different kinematics.
AB  - INTRODUCTION: Vertical root fracture is a common finding in endodontically
      treated teeth, notably oval roots. The aim of the present study was to determine
      the effect of instrumentation kinematics and the material of instrument
      construction of single-file systems on dentin walls and fracture resistance of
      oval roots. METHODS: Sixty-five roots with oval canals were allocated into a
      control group (n = 5) and 3 experimental groups of 20 roots each. Group WO was
      instrumented with the WaveOne primary file (Dentsply Maillefer, Baillagues,
      Switzerland), group PT-Rec was prepared with F2 ProTaper files (Dentsply
      Maillefer, Baillagues, Switzerland) used in a reciprocating motion, and group PT
      Rot was prepared with F2 ProTaper files used in a rotation motion. For crack
      evaluation, half of the samples (n = 30) were embedded in acrylic resin, and the
      blocks were sectioned at 3, 6, and 9 mm from the apex. The sections were examined
      under a stereomicroscope and scored for crack presence. The other half of the
      specimens (n = 30) were obturated using lateral condensation of gutta-percha and
      AdSeal sealer (Meta Biomed Co, Ltd, Chungbuk, Korea). The specimens were then
      subjected to a load of 1 mm/min to determine the force required to fracture the
      roots. RESULTS: WaveOne instruments induced the least amount of cracks and
      exhibited greatest resistance to fracture compared with ProTaper F2 files whether
      used in reciprocating or rotating motions. CONCLUSIONS: The alloy from which the
      material is manufactured is a more important factor determining the dentin
      damaging potential of single-file instruments than the motion of instrumentation.

PMID- 24862716
TI  - Comparative study of different novel nickel-titanium rotary systems for root
      canal preparation in severely curved root canals.
AB  - INTRODUCTION: We compared the effects of 6 different rotary systems on
      transportation, canal curvature, centering ratio, surface area, and volumetric
      changes of curved mesial root canals of mandibular molar via cone-beam computed
      tomographic (CBCT) imaging. METHODS: Mesiobuccal root canals of 120 mandibular
      first molars with an angle of curvature ranging from 20 degrees -40 degrees  were
      divided into 6 groups of 20 canals. Based on CBCT images taken before
      instrumentation, the groups were balanced with respect to the angle and radius of
      canal curvature. Root canals were shaped with the following systems with an
      apical size of 25: OneShape (OS) (MicroMega, Besancon, France), ProTaper
      Universal (PU) F2 (Dentsply Maillefer, Ballaigues, Switzerland), ProTaper Next X2
      (Dentsply Maillefer), Reciproc (R) R25 (VDW, Munich, Germany), Twisted File
      Adaptive (TFA) SM2 (SybronEndo, Orange, CA), and WaveOne primary (Dentsply Tulsa
      Dental Specialties, Tulsa, OK). After root canal preparation, changes were
      assessed with CBCT imaging. The significance level was set at P = .05. RESULTS:
      The R system removed a significantly higher amount of dentin than the OS, PU, and
      TFA systems (P < .05). There was no significant difference among the 6 groups in
      transportation, canal curvature, changes of surface area, and centering ratio
      after instrumentation. CONCLUSIONS: The 6 different file systems straightened
      root canal curvature similarly and produced similar canal transportation in the
      preparation of mesial canals of mandibular molars. R instrumentation exhibited
      superior performance compared with the OS, TFA, and PU systems with respect to
      volumetric change.

PMID- 24862717
TI  - Visualization of removal of trapped air from the apical region of the straight
      root canal models generating 2-phase intermittent counter flow during
      ultrasonically activated irrigation.
AB  - INTRODUCTION: The purpose of this in vitro study was to obtain a better
      understanding of the mechanism of irrigant traveling apically and generating 2
      phase intermittent counter flow in straight root canal models during activation
      of the irrigant by ultrasonic means in an endodontic procedure. METHODS: A high
      speed imaging system, with high temporal and spatial resolution (FastCam SA5;
      Photron, Tokyo, Japan) at a frame rate of 100,000 frames per second using a macro
      lens (60 mm, f/2.8; Nikon, Tokyo, Japan), was used to visualize, in glass models
      of root canals, an ultrasonically induced acoustic pressure wave in an EDTA
      solution environment. A 25-mm stainless steel noncutting file #20 driven by an
      ultrasonic device (P5 Newtron; Satelec Acteon, Merignac, France) at power
      settings of 5 and 7 produced disturbances at the solution-air interface. RESULTS:
      We found that apically directed travel of the irrigant was caused by disruption
      of the surface tension at the solution-air interface. This disruption caused by
      ultrasonic activation energy displaced air in the form of bubbles from the apical
      region toward the solution. CONCLUSIONS: The apical movement of the solution may
      be attributed to ultrasonically induced wave generation at the solution-air
      interface, resulting in the removal of trapped air from the root canal and
      allowing the solution to travel apically in the opposite directions (via a 2
      phase intermittent counter flow).

PMID- 24862718
TI  - The effect of different final irrigant activation techniques on the bond strength
      of an epoxy resin-based endodontic sealer: a preliminary study.
AB  - INTRODUCTION: The aim of this study was to evaluate whether or not different
      final irrigation activation techniques affect the bond strength of an epoxy resin
      based endodontic sealer (AH Plus; Dentsply DeTrey, Konstanz, Germany) to the root
      canal walls of different root thirds. METHODS: Eighty single-rooted human
      mandibular premolars were prepared by using the ProTaper system (Dentsply
      Maillefer, Ballaigues, Switzerland) to size F4, and a final irrigation regimen
      using 3% sodium hypochlorite and 17% EDTA was performed. The specimens were
      randomly divided into 4 groups (n = 20) according to the final irrigation
      activation technique used as follows: no activation (control), manual dynamic
      activation (MDA), CanalBrush (Coltene Whaledent, Altststten, Switzerland)
      activation, and ultrasonic activation. Five specimens from each group were
      prepared for scanning electron microscopic observation to assess the smear layer
      removal after the final irrigation procedures. All remaining roots were then
      obturated with gutta-percha and AH Plus sealer. A push-out test was used to
      measure the bond strength between the root canal dentin and AH Plus sealer. The
      data obtained from the push-out test were analyzed using 2-way analysis of
      variance and Tukey post hoc tests. RESULTS: The bond strength values mostly
      decreased in the coronoapical direction (P < .001). In the coronal and middle
      thirds, ultrasonic activiation showed a higher bond strength than other groups (P
      < .05). In the apical third, MDA displayed the highest bond strength to root
      dentin (P < .05). The majority of specimens exhibited cohesive failures.
      CONCLUSIONS: The bond strength of AH Plus sealer to root canal dentin may improve
      with ultrasonic activation in the coronal and middle thirds and MDA in the apical
      third.

PMID- 24862719
TI  - Evaluation of a new filing system's ability to maintain canal morphology.
AB  - INTRODUCTION: The manufacturer of the Hyflex CM endodontic files claims the files
      remain centered within the canal, and if unwound during treatment, they will
      regain their original shape after sterilization. The purpose of this study was to
      evaluate and compare the canal centering ability of the Hyflex CM and the ProFile
      ISO filing systems after repeated uses in simulated canals, followed by
      autoclaving. METHODS: Sixty acrylic blocks with a canal curvature of 45 degrees 
      were stained with methylene blue, photographed, and divided into 2 groups, H
      (Hyflex CM) and P (ProFile ISO). The groups were further subdivided into 3
      subgroups: H1, H2, H3; P1, P2, P3 (n = 10). Groups H1 and P1 were instrumented to
      40 (.04) with the respective file system. Used files were autoclaved for 26
      minutes at 126 degrees C. After sterilization, the files were used to instrument
      groups H2 and P2. The same sterilization and instrumentation procedure was
      repeated for groups H3 and P3. Post-instrumentation digital images were taken and
      superimposed over the pre-instrumentation images. Changes in the location of the
      center of the canal at predetermined reference points were recorded and compared
      within subgroups and between filing systems. RESULTS: Statistical differences in
      intergroup and intragroup transportation measures were analyzed by using the
      Kruskal-Wallis analysis of variance of ranks with the Bonferroni post hoc test.
      There was a difference between Hyflex CM and ProFile ISO groups, although it was
      not statistically significant. Intragroup differences for both Hyflex CM and
      ProFile ISO groups were not significant (P < .05). CONCLUSIONS: The Hyflex CM and
      ProFile ISO files equally maintained the original canal's morphology after 2
      sterilization cycles.

PMID- 24862720
TI  - Root and root canal morphology in maxillary second molar with fused root from a
      native Chinese population.
AB  - INTRODUCTION: Root fusion is an anatomic variation in maxillary second molars
      (MSMs); however, the nature of this canal morphology as it relates to its root
      anatomy has not been fully clarified. The purpose of this study was to
      investigate the relationship between features of fused roots and root canal
      anatomy in MSMs using micro-computed tomographic imaging. METHODS: One hundred
      eighty-seven extracted MSMs were scanned with the MUCT50 (Scanco Medical,
      Bassersdorf, Switzerland), and their root and canal morphology was classified and
      analyzed using the classifications proposed by Yang and Vertucci. The number and
      position of canals that merged were recorded and compared among different root
      fusion types. RESULTS: One hundred eight (57.75%) MSMs had 3 separate roots, and
      79 (42.25%) had fused roots. Of the 79 fused roots, 22 showed partial canal
      merging, and 6 had complete canal merging. Canal merging was found with teeth
      with 3-root fusion more often than in those with 2-root fusion (P < .05). Of 28
      merged canals, 16 occurred between mesiobuccal and distobuccal canals and 9 among
      mesiobuccal, distobuccal, and palatal canals. CONCLUSIONS: MSMs with fused roots
      may present a complicated root canal system as a result of canal merging.

PMID- 24862721
TI  - Effect of EDTA, sodium hypochlorite, and chlorhexidine gluconate with or without
      surface modifiers on dentin microhardness.
AB  - INTRODUCTION: This study aimed to evaluate the effects of root canal irrigants on
      the microhardness of root canal dentin in the presence and absence of surface
      modifying agents. METHODS: Forty-eight root halves were prepared by longitudinal
      splitting of the distal roots of 24 freshly extracted mandibular human third
      molars and embedded in autopolymerizing acrylic resin, leaving the dentin surface
      exposed. After polishing, the microhardness values of the untreated dentin
      surfaces were recorded by using Vickers tester at the mid-root level. The root
      halves were randomly assigned to 6 groups composed of 8 samples each and treated
      for 5 minutes with one of the following irrigants: 17% EDTA, REDTA, 2%
      chlorhexidine gluconate (CHX), 2% CHX with surface modifiers (CHX-Plus), 6%
      NaOCl, or 6% NaOCl with surface modifiers (Chlor-XTRA). After surface treatment,
      dentin microhardness values were recorded at close proximity to the initial
      indentation areas. Experimental data were statistically analyzed by using the t
      test and one-way analysis of variance, followed by Tukey honestly significant
      difference test at alpha = 0.05. RESULTS: EDTA, REDTA, NaOCl, and Chlor-XTRA
      significantly decreased the microhardness of root dentin compared with intact
      controls (P < .05). CONCLUSIONS: The addition of surface modifiers to the
      irrigants did not affect the microhardness of the samples.

PMID- 24862722
TI  - Orbital, mediastinal, and cervicofacial subcutaneous emphysema after endodontic
      retreatment of a mandibular premolar: a case report.
AB  - INTRODUCTION: Subcutaneous emphysema (SCE) rarely occurs from endodontic
      treatment. Most reported cases of iatrogenic SCE occur in the cervicofacial
      region. Only a few cases have been reported of SCE extending into the mediastinum
      or orbital spaces. In the present report, we describe a concomitant occurrence of
      orbital, mediastinal, and cervicofacial SCE immediately after endodontic
      retreatment. METHODS: A 33-year-old woman presented to the hospital with acute
      swelling of the right side of her face and neck. Earlier in the day, she began
      experiencing rapid swelling while undergoing endodontic retreatment of a
      mandibular right first premolar by her general dentist. The dentist immediately
      referred the case to an oral surgeon who then ordered additional tests and
      radiographic studies at the hospital. From there, the patient received
      consultation and comprehensive treatment by a multidisciplinary team of medical
      and dental staff. RESULTS: Physical examination, laboratory tests, and computed
      tomographic studies confirmed a diagnosis of SCE. Extensive air pockets were
      detected within the orbital, mediastinum, and cervicofacial spaces. The patient
      was admitted to the hospital and underwent treatment and observation for massive
      SCE with likely secondary infection. On the fifth day, she was discharged after
      showing dramatic improvement. CONCLUSIONS: SCE may go undetected or misdiagnosed.
      Complications may be fatal. Therefore, clinicians should apply preventive
      measures and know how to identify and manage SCE. We review reports of SCE in the
      last century, discuss etiology and differential diagnosis, and present
      recommendations for prevention and management of SCE.

PMID- 24862723
TI  - Loss of frugivore seed dispersal services under climate change.
AB  - The capacity of species to track shifting climates into the future will strongly
      influence outcomes for biodiversity under a rapidly changing climate. However, we
      know remarkably little about the dispersal abilities of most species and how
      these may be influenced by climate change. Here we show that climate change is
      projected to substantially reduce the seed dispersal services provided by
      frugivorous vertebrates in rainforests across the Australian Wet Tropics. Our
      model projections show reductions in both median and long-distance seed
      dispersal, which may markedly reduce the capacity of many rainforest plant
      species to track shifts in suitable habitat under climate change. However, our
      analyses suggest that active management to maintain the abundances of a small set
      of important frugivores under climate change could markedly reduce the projected
      loss of seed dispersal services and facilitate shifting distributions of
      rainforest plant species. 

PMID- 24862725
TI  - Electronic care records - can they fulfil their promise?

PMID- 24862726
TI  - Focusing on special sections.

PMID- 24862724
TI  - A new method of sweat testing: the CF Quantum(r)sweat test.
AB  - BACKGROUND: Conventional methods of sweat testing are time consuming and have
      many steps that can and do lead to errors. This study compares conventional sweat
      testing to a new quantitative method, the CF Quantum(r) (CFQT) sweat test. This
      study tests the diagnostic accuracy and analytic validity of the CFQT. METHODS:
      Previously diagnosed CF patients and patients who required a sweat test for
      clinical indications were invited to have the CFQT test performed. Both
      conventional sweat testing and the CFQT were performed bilaterally on the same
      day. Pairs of data from each test are plotted as a correlation graph and Bland
      Altman plot. Sensitivity and specificity were calculated as well as the means and
      coefficient of variation by test and by extremity. After completing the study,
      subjects or their parents were asked for their preference of the CFQT and
      conventional sweat testing. RESULTS: The correlation coefficient between the CFQT
      and conventional sweat testing was 0.98 (95% confidence interval: 0.97-0.99). The
      sensitivity and specificity of the CFQT in diagnosing CF was 100% (95% confidence
      interval: 94-100%) and 96% (95% confidence interval: 89-99%), respectively. In
      one center in this three center multicenter study, there were higher sweat
      chloride values in patients with CF and also more tests that were invalid due to
      discrepant values between the two extremities. The percentage of invalid tests
      was higher in the CFQT method (16.5%) compared to conventional sweat testing
      (3.8%) (p < 0.001). In the post-test questionnaire, 88% of subjects/parents
      preferred the CFQT test. CONCLUSIONS: The CFQT is a fast and simple method of
      quantitative sweat chloride determination. This technology requires further
      refinement to improve the analytic accuracy at higher sweat chloride values and
      to decrease the number of invalid tests.

PMID- 24862727
TI  - Advances in automated image analysis.

PMID- 24862732
TI  - Role of periodontal ligament fibroblasts in osteoclastogenesis: a review.
AB  - During the last decade it has become clear that periodontal ligament fibroblasts
      may contribute to the in vitro differentiation of osteoclasts. We surveyed the
      current findings regarding their osteoclastogenesis potential. Periodontal
      ligament fibroblasts have the capacity to select and attract osteoclast
      precursors and subsequently to retract and enable migration of osteoclast
      precursors to the bone surface. There, fusion of precursors takes place, giving
      rise to osteoclasts. The RANKL-RANK-osteoprotegerin (OPG) axis is considered
      crucial in this process. Periodontal ligament fibroblasts produce primarily OPG,
      an osteoclastogenesis-inhibitory molecule. However, they may be influenced in
      vivo by direct or indirect interactions with bacteria or by mechanical loading.
      Incubation of periodontal ligament fibroblasts with bacteria or bacterial
      components causes an increased expression of RANKL and other osteoclastogenesis
      stimulating molecules, such as tumor necrosis factor-alpha and macrophage-colony
      stimulating factor. Similar results are observed after the application of
      mechanical loading to these fibroblasts. Periodontal ligament fibroblasts may be
      considered to play an important role in the remodelling of alveolar bone. In
      vitro experiments have demonstrated that periodontal ligament fibroblasts adapt
      to bacterial and mechanical stimuli by synthesizing higher levels of
      osteoclastogenesis-stimulating molecules. Therefore, they probably contribute to
      the enhanced osteoclast formation observed during periodontitis and to
      orthodontic tooth movement. 

PMID- 24862733
TI  - Clinical experience of combined HeartWare ventricular assist device and
      implantable cardioverter defibrillator therapy.
AB  - INTRODUCTION: The HeartWare continuous flow ventricular assist device (HVAD) is
      used in an increasing number of heart failure patients. In those patients,
      ventricular arrhythmias (VAs) are common and, consequently, many patients already
      have an implanted implantable cardioverter defibrillator (ICD) in place or
      receive ICD implantation after left ventricular assist device implantation.
      However, limited data on feasibility and necessity of combined ICD and HVAD
      therapy are available. In this study we present our technical and clinical
      experience. METHODS AND RESULTS: Between 01/2010 and 06/2013, 41 patients
      received HVAD implantation. Twenty-six HVAD patients who already had an ICD
      device placed prior to HVAD implantation or received ICD implantation afterwards
      were enrolled in this study. Peri- and postoperative complications as well as ICD
      interrogations were documented and analyzed retrospectively. Mean patients age
      was 58.4 +/- 12.6 years; 88.5% of patients were male. During mean follow-up of
      12.2 +/- 8.9 months, appropriate ICD interventions occurred in 9 patients (34.6%)
      due to ventricular tachyarrhythmia (n = 7) or ventricular fibrillation (n = 2).
      An inappropriate ICD intervention was seen in 1 patient (3.9%) due to tachycardic
      atrial fibrillation. Patients on HVAD with a history of VAs (n = 13) had a
      significantly higher incidence of ICD interventions compared to patients with
      primary prophylactic indication for ICD (n = 13; 53.8% vs. 7.7%; P = 0.015). No
      disturbance of ICD function was seen after HVAD implantation. CONCLUSION:
      Combined ICD and HVAD therapy was safe and feasible, without electromagnetic
      interference between ICD and ventricular assist device. The incidence of ICD
      interventions was high in patients with a history of VAs, but low in patients
      with ICD implantation for primary prevention.

PMID- 24862734
TI  - Promotion and nucleation of carbonate precipitation during microbial iron
      reduction.
AB  - Iron-bearing early diagenetic carbonate cements are common in sedimentary rocks,
      where they are thought to be associated with microbial iron reduction. However,
      little is yet known about how local environments around actively iron-reducing
      cells affect carbonate mineral precipitation rates and compositions.
      Precipitation experiments with the iron-reducing bacterium Shewanella oneidensis
      MR-1 were conducted to examine the potential role of cells in promoting
      precipitation and to explore the possible range of precipitate compositions
      generated in varying fluid compositions. Actively iron-reducing cells induced
      increased carbonate mineral saturation and nucleated precipitation on their
      poles. However, precipitation only occurred when calcium was present in solution,
      suggesting that cell surfaces lowered local ferrous iron concentrations by
      adsorption or intracellular iron oxide precipitation even as they locally raised
      pH. Resultant precipitates were a range of thermodynamically unstable calcium
      rich siderites that would likely act as precursors to siderite, calcite, or even
      dolomite in nature. By modifying local pH, providing nucleation sites, and
      altering metal ion concentrations around cell surfaces, iron-reducing micro
      organisms could produce a wide range of carbonate cements in natural sediments. 

PMID- 24862736
TI  - Use of tissue oxygenation (StO2) monitor in the ED.

PMID- 24862735
TI  - In vitro reconstitution of a cellular phase-transition process that involves the
      mRNA decapping machinery.
AB  - In eukaryotic cells, components of the 5' to 3' mRNA degradation machinery can
      undergo a rapid phase transition. The resulting cytoplasmic foci are referred to
      as processing bodies (P-bodies). The molecular details of the self-aggregation
      process are, however, largely undetermined. Herein, we use a bottom-up approach
      that combines NMR spectroscopy, isothermal titration calorimetry, X-ray
      crystallography, and fluorescence microscopy to probe if mRNA degradation factors
      can undergo phase transitions in vitro. We show that the Schizosaccharomyces
      pombe Dcp2 mRNA decapping enzyme, its prime activator Dcp1, and the scaffolding
      proteins Edc3 and Pdc1 are sufficient to reconstitute a phase-separation process.
      Intermolecular interactions between the Edc3 LSm domain and at least 10 helical
      leucine-rich motifs in Dcp2 and Pdc1 build the core of the interaction network.
      We show that blocking of these interactions interferes with the clustering
      behavior, both in vitro and in vivo. 

PMID- 24862739
TI  - Author's Responce to the Letter to the Editor.

PMID- 24862737
TI  - G-protein coupled estrogen receptor, estrogen receptor alpha, and progesterone
      receptor immunohistochemistry in the hypothalamus of aging female rhesus macaques
      given long-term estradiol treatment.
AB  - Steroid hormone receptors are widely and heterogeneously expressed in the brain,
      and are regulated by age and gonadal hormones. Our goal was to quantify effects
      of aging, long-term estradiol (E2 ) treatment, and their interactions, on
      expression of G protein-coupled estrogen receptor (GPER), estrogen receptor alpha
      (ERalpha) and progesterone receptor (PR) immunoreactivity in two hypothalamic
      regions, the arcuate (ARC) and the periventricular area (PERI) of rhesus monkeys
      as a model of menopause and hormone replacement. Ovariectomized (OVX) rhesus
      macaques were young (~ 11 years) or aged (~ 25 years), given oil (vehicle) or E2
      every 3 weeks for 2 years. Immunohistochemistry and stereologic analysis of
      ERalpha, PR, and GPER was performed. More effects were detected for GPER than the
      other two receptors. Specifically, GPER cell density in the ARC and PERI, and the
      percent of GPER-immunoreactive cells in the PERI, were greater in aged than in
      young monkeys. In addition, we mapped the qualitative distribution of GPER in the
      monkey hypothalamus and nearby regions. For ERalpha, E2 treated monkeys tended to
      have higher cell density than vehicle monkeys in the ARC. The percent of PR
      density in the PERI tended to be higher in E2 than vehicle monkeys of both ages.
      This study shows that the aged hypothalamus maintains expression of hormone
      receptors with age, and that long-term cyclic E2 treatment has few effects on
      their expression, although GPER was affected more than ERalpha or PR. This result
      is surprising in light of evidence for E2 regulation of the receptors studied
      here, and differences may be due to the selected regions, long-term nature of E2
      treatment, among other possibilities.

PMID- 24862740
TI  - Attitudes towards young people who self-harm: age, an influencing factor.
AB  - AIM: To determine the attitudes of emergency care staff towards young people
      (aged 12-18 years) who self-harm and to gain an understanding of the basis of
      attitudes that exist. BACKGROUND: Young people frequently attend emergency
      services following self-harm; it is unclear whether being a young person
      influences attitudes held. DESIGN: Mixed methods using a triangulation convergent
      design. METHODS: Survey of 143 staff members from four accident & emergency
      departments and one ambulance service. Semi-structured interviews with seven
      children's A&E nurses and five ambulance personnel from the same locality. Data
      were collected during 2010. RESULTS/FINDINGS: Pearson's product moment
      correlation coefficient confirmed a strong positive correlation between scores on
      the two scales used to measure attitudes; paired samples t-test revealed a
      statistically significant difference in scores across the scales; practitioners
      held more positive attitudes towards young people who self-harmed than young
      people per se. Both data sets confirmed the presence of ambivalence and ambiguity
      in attitudes held. The qualitative data revealed that because of their age and
      immaturity young people were not held responsible for their self-harming
      behaviours. Being young did though influence subsequent admission, with
      particular difficulty in securing admission for those aged 16-17 reported.
      CONCLUSION: Age is a factor in shaping practitioners' attitudes; age also directs
      and influences a young person's journey through emergency care, although due to
      ambiguity there is inconsistency in determining where those aged 16-17 years of
      age fit.

PMID- 24862738
TI  - The Cav1.2 N terminus contains a CaM kinase site that modulates channel
      trafficking and function.
AB  - The L-type voltage-gated calcium channel Cav1.2 and the calcium-activated CaM
      kinase cascade both regulate excitation transcription coupling in the brain. CaM
      kinase is known to associate with the C terminus of Cav1.2 in a region called the
      PreIQ-IQ domain, which also binds multiple calmodulin molecules. Here we identify
      and characterize a second CaMKII binding site in the N terminus of Cav1.2 that is
      formed by a stretch of four amino residues (cysteine-isoleucine-serine
      isoleucine) and which regulates channel expression and function. By using live
      cell imaging of tsA-201 cells we show that GFP fusion constructs of the CaMKII
      binding region, termed N2B-II co-localize with mCherry-CaMKII. Mutating CISI to
      AAAA ablates binding to and colocalization with CaMKII. Cav1.2-AAAA channels show
      reduced cell surface expression in tsA-201 cells, but interestingly, display an
      increase in channel function that offsets the trafficking deficit. Altogether our
      data reveal that the proximal N terminus of Cav1.2 contains a CaMKII binding
      region which contributes to channel surface expression and function.

PMID- 24862741
TI  - Time of hepatocellular carcinoma recurrence after liver resection and alpha
      fetoprotein are important prognostic factors for salvage liver transplantation.
AB  - Salvage liver transplantation (LT) is considered a feasible option for the
      treatment of recurrent hepatocellular carcinoma (HCC). We performed this
      multicenter study to assess the risk factors associated with the recurrence of
      HCC and patient survival after salvage LT. Between January 2000 and December
      2011, 101 patients who had previously undergone liver resection (LR) for HCC
      underwent LT at 3 transplant centers in Korea. Sixty-nine patients' data were
      retrospectively reviewed for the analysis. The recurrence of HCC was diagnosed at
      a median of 10.6 months after the initial LR, and patients underwent salvage LT.
      Recurrences were within the Milan criteria in 48 cases and were outside the Milan
      criteria in 21 cases. After salvage LT, 31 patients had HCC recurrence during a
      median follow-up period of 24.5 months. There were 24 deaths, and 20 were due to
      HCC recurrence. The 5-year overall survival rate was approximately 54.6%, and the
      5-year recurrence-free survival rate was 49.3%. HCC recurrence within the 8
      months after LR [hazard ratio (HR) = 3.124, P = 0.009], an alpha-fetoprotein
      level higher than 200 ng/mL (HR = 2.609, P = 0.02), and HCC outside the Milan
      criteria at salvage LT (HR = 2.219, P = 0.03) were independent risk factors for
      poor recurrence-free survival after salvage LT. In conclusion, the timing and
      extent of HCC recurrence after primary LR both play significant roles in the
      outcome of salvage LT.

PMID- 24862742
TI  - The effects of methylphenidate on whole brain intrinsic functional connectivity.
AB  - Methylphenidate (MPH) is an indirect dopaminergic and noradrenergic agonist that
      is used to treat attention deficit hyperactivity disorder and that has shown
      therapeutic potential in neuropsychiatric diseases such as depression, dementia,
      and Parkinson's disease. While effects of MPH on task-induced brain activation
      have been investigated, little is known about how MPH influences the resting
      brain. To investigate the effects of 40 mg of oral MPH on intrinsic functional
      connectivity, we used resting state fMRI in 54 healthy male subjects in a double
      blind, randomized, placebo-controlled study. Functional connectivity analysis
      employing ICA revealed seven resting state networks (RSN) of interest.
      Connectivity strength between the dorsal attention network and the thalamus was
      increased after MPH intake. Other RSN located in association cortex areas, such
      as the left and right frontoparietal networks and the executive control network,
      showed MPH-induced connectivity increase to sensory-motor and visual cortex
      regions and connectivity decrease to cortical and subcortical components of
      cortico-striato-thalamo-cortical circuits (CST). RSN located in sensory-motor
      cortex areas showed the opposite pattern with MPH-induced connectivity increase
      to CST components and connectivity decrease to sensory-motor and visual cortex
      regions. Our results provide evidence that MPH does not only alter intrinsic
      connectivity between brain areas involved in sustained attention, but that it
      also induces significant changes in the cortico-cortical and cortico-subcortical
      connectivity of many other cognitive and sensory-motor RSN.

PMID- 24862743
TI  - Distinct age-matched serum biomarker profiles in patients with cutaneous T-cell
      lymphoma.
AB  - Immunological functions decline with age. Because MS/SzS predominately affects
      the elderly, it is important to distinguish age-related from cancer-specific
      changes. Also, MF and SzS are malignancies of CD4(+) T-lymphocytes, further
      compromising an immune state of the patients. The objectives of this study were
      to distinguish disease-specific immunological deterioration by performing
      comparative age-matched Luminex multiplex assessment of 34 serum biomarkers
      between patients with MF/SzS, HIV-infected individuals and normal controls.
      Controlling for age, expression level appears to significantly differ between
      patients with MF/SzS and controls for the following biomarkers: G-CSF, IL-5, MIP
      1beta, TNF-alpha, VEGF, EOTAXIN, IL-8, IL-12, IL-2R, IP10, MCP-1, MIG, TNFR1 and
      TNFR2 (P < 0.05), while others showed normal age-related changes. Interestingly,
      cluster analysis placed MF/SzS profiles closer to HIV. This further underscores
      an immunologically compromised state of patients with MF/SzS and suggests its
      potential self-perpetuating role in disease progression. 

PMID- 24862745
TI  - Paediatric rheumatology: a subspecialty in its infancy that is making leaps and
      bounds.
AB  - Paediatric rheumatology is an exciting field exploding with new knowledge of
      autoimmune and autoinflammatory conditions and how to treat them. It is, however,
      a relatively new subspecialisation in Asia. There is thus a great need to educate
      the public and medical community about paediatric rheumatic diseases so that
      children with such conditions are given the highest possibility of achieving
      normal function in their daily lives. 

PMID- 24862744
TI  - Recurrent wheeze and cough in young children: is it asthma?
AB  - A clinical diagnosis of asthma is often considered when a child presents with
      recurrent cough, wheeze and breathlessness. However, there are many other causes
      of wheeze in a young child. These range from recurrent viral infections to
      chronic suppurative lung disease, gastro-oesophageal reflux disease and rare
      structural abnormalities. Arriving at a diagnosis includes taking into
      consideration the symptomatology, triggers, atopic features, family history,
      absence of red flags and therapeutic trial, where indicated. 

PMID- 24862746
TI  - Food allergy in Singapore: opening a new chapter.
AB  - With the exception of shellfish, the overall food allergy rates in Singapore have
      not reached the epidemic proportions of the West. The rates of egg, milk and fish
      allergies remain low. However, the patterns of some food allergies in Singapore
      have changed over the last decade. For example, peanut allergy, once rare in
      Singapore, is now the most common cause of anaphylaxis in children. Studies
      analysing lifestyle practices, particularly with respect to prevention of food
      allergy, are necessary in order for practitioners to understand global
      differences and maintain this low prevalence. 

PMID- 24862747
TI  - Intra-articular glucocorticoid injections in patients with juvenile idiopathic
      arthritis in a Singapore hospital.
AB  - INTRODUCTION: This study aimed to evaluate the efficacy and safety of intra
      articular glucocorticoid (IAG) injections in our institution in children with
      juvenile idiopathic arthritis (JIA). METHODS: This is a retrospective assessment
      of IAG injections performed by the Department of Paediatrics, National University
      Hospital, Singapore, from October 2009 to October 2011. A total of 26 procedures
      were evaluated for efficacy, considering parameters such as clinical response,
      changes in systemic medication, length of time between repeat injections, safety,
      consent-taking, pre- and post-procedural advice, compliance with aseptic
      technique, and post-procedural complications. RESULTS: A total of 26 IAG
      injections of triamcinolone hexacetonide were administered over 17 occasions
      (i.e. patient encounters) to ten patients with JIA during the study period. After
      the injections, clinical scoring by a paediatric rheumatologist showed overall
      improvement by an average of 2.62 points out of 15. Besides six patient
      encounters that had an increase in systemic medication on the day of the
      injection, five required an increase within six months post injection, two
      required no adjustments, and one resulted in a decrease in medications. In all,
      21 injections did not require subsequent injections. The mean interval between
      repeat injections was 7.8 months. Cutaneous side effects were noted in three
      anatomically difficult joints. Medical documentation with regard to patient
      progress was found to be lacking. CONCLUSION: As per the recommendations of the
      American College of Rheumatology, we safely used IAG injections as the first-line
      therapy in our group of patients with oligoarticular JIA, and/or as an adjunct to
      systemic therapy in our patients with JIA.

PMID- 24862748
TI  - Clinical profile and visual outcome of traumatic paediatric cataract in suburban
      Malaysia: a ten-year experience.
AB  - INTRODUCTION: Available data on traumatic cataract in Asian children is primarily
      confined to South Asian countries. We aimed to describe the demographics, nature
      of injury and visual outcomes of Malaysian children with traumatic cataract from
      a suburban area, and discuss the literature on Asian children with this
      condition. METHODS: We conducted a retrospective study of 29 children below 17
      years of age who were diagnosed with traumatic paediatric cataract and who
      attended Hospital Universiti Sains Malaysia, Kelantan, Malaysia, between January
      2000 and December 2010. Follow-up periods ranged from 12 to 120 months.
      Demographic data, clinical features, mechanism and extent of injury, and final
      visual outcome were recorded. RESULTS: The study population was predominantly
      male. The right eye was injured in 62.07% of patients. A majority of patients had
      penetrating injuries, with the most common cause being injury by an organic
      foreign body (24.14%). Presenting visual acuity worse than 6/60 was observed in
      68.97% of patients. Only 34.48% of patients had a final corrected visual acuity
      of 6/12 and better. 55.18% of patients were operated on within less than one
      month of their injuries. A majority of children sustained concurrent injuries to
      the anterior segment structures. Corneal opacity and amblyopia were the most
      common causes of poor final visual acuity. CONCLUSION: Health education and
      awareness are essential tools that can prevent avoidable blindness due to
      traumatic cataract in the paediatric population. The importance of rehabilitation
      programmes for these patients should be emphasised.

PMID- 24862749
TI  - Sleep-related breathing disorder is associated with hyperactivity in
      preschoolers.
AB  - INTRODUCTION: Sleep problems are a prominent feature in children with attention
      deficit hyperactivity disorder (ADHD). Unlike existing studies that focused on
      extreme samples (i.e. normal vs. ADHD), our study investigated the associations
      of sleep-related behaviours and ADHD features in nonclinical Chinese
      preschoolers. METHODS: All participants were recruited via advertisements and
      screened for eligibility through a telephone interview prior to an onsite visit.
      The maternal reports of the Conners' Parent Rating Scale (CPRS) and Pediatric
      Sleep Questionnaire (PSQ) were acquired from 110 Chinese preschoolers aged six
      years. Regression models were used to examine the association between CPRS and
      PSQ scores. RESULTS: The results obtained from regression models on the CPRS and
      PSQ scores of the 110 participants showed that none of the sleep-related
      behavioural measures (i.e. sleep-related breathing disorder [SRBD], snoring,
      daytime sleepiness, restless legs syndrome) was associated with inattention in
      our sample. However, worse SRBD was associated with higher hyperactivity.
      CONCLUSION: Our study underpins the importance of understanding the relationship
      between sleep-related behaviours and ADHD characteristics before the usual age of
      clinical diagnosis in children with ADHD.

PMID- 24862750
TI  - Clinical characteristics and mortality risk prediction in critically ill children
      in Malaysian Borneo.
AB  - INTRODUCTION: Mortality risk prediction scores are important for benchmarking
      quality of care in paediatric intensive care units (PICUs). We aimed to benchmark
      PICU outcomes at our hospital against the Pediatric Index of Mortality 2 (PIM2)
      mortality risk prediction score, and evaluate differences in diagnosis on
      admission and outcomes between Malaysian and immigrant children. METHODS: We
      prospectively collected demographic and clinical data on paediatric medical
      patients admitted to the PICU of Sabah Women's and Children's Hospital in Kota
      Kinabalu, Sabah, Malaysia. The PIM2 risk score for mortality was tabulated.
      RESULTS: Of the 131 patients who met the inclusion criteria, data was available
      for 115 patients. The mean age of the patients was 2.6 +/- 3.8 years, with 79% of
      the cohort aged less than five years. Patients were mainly of Kadazan (38%) and
      Bajau (30%) descent, and 26% of patients were non-citizens. Leading diagnoses on
      admission were respiratory (37%), neurological (18%) and infectious (17%)
      disorders. Out of the 29 patients who died, 23 (79%) were Malaysians and the main
      mortality diagnostic categories were respiratory disorder (22%), septicaemia
      (22%), haemato-oncological disease (17%) and neurological disorder (13%).
      Calculated standardised mortality ratios (SMRs) were not significantly > 1 for
      any patient category for variables such as age and admission diagnosis. However,
      infants less than two years old with comorbidities were significantly worse (SMR
      2.61, 95% confidence interval 1.02-6.66). CONCLUSION: The patient profile at our
      centre was similar to that reported from other PICUs in Asia. The PIM2 score is a
      useful mortality risk prediction model for our population.

PMID- 24862751
TI  - Comparison of two regimens of vitamin D supplementation for vitamin D-deficient
      neonates.
AB  - INTRODUCTION: Vitamin D deficiency is common in pregnant women, and
      supplementation of vitamin D is necessary for the infants of these women. This
      study explored the efficacy of an alternative way of vitamin D supplementation in
      an area with a high prevalence of vitamin D deficiency in mothers. METHODS: This
      was a non-randomised clinical trial conducted in 2010 in Yazd, Iran. Full-term
      healthy infants born to vitamin D-deficient mothers (n = 82) were divided into
      the high-dose regimen (HDR; single oral bolus 30,000 IU vitamin D3, n = 34) and
      the standard-dose regimen (SDR; 400 IU/day vitamin D3 within two weeks of life, n
      = 48) groups. 25-hydroxyvitamin D (25OHD) was measured using chemiluminescent
      immunoassays, and 25OHD level > 20 ng/mL was deemed sufficient. RESULTS: Over 90%
      of infants in the HDR group attained vitamin D sufficiency within one month,
      while comparable sufficiency was reached in the SDR group only after four months.
      At two months, the proportion of infants attaining 25OHD > 30 ng/mL was 93.3% and
      27.9% in the HDR and SDR groups, respectively (p = 0.003). None of our infants
      achieved 25OHD levels > 100 ng/mL. CONCLUSION: For infants born to vitamin D
      deficient mothers, oral supplementation of 30,000 IU vitamin D3 during the first
      month of life, followed by a routine recommended dose of 400 IU/day, should be
      considered. The four-month lag for attaining vitamin D sufficiency in 90% of
      infants in the SDR group may have clinical implications and should be further
      investigated.

PMID- 24862753
TI  - Clinics in diagnostic imaging (152). Right lower lobe segmental pulmonary
      embolus.
AB  - A 56-year-old man presented to the Accident and Emergency Department with
      pleuritic chest pain of sudden onset. He gave a history of short-distance air
      travel ten days earlier. Chest radiograph showed a peripheral-based opacity in
      the right lower zone, which was not seen in a previous study done three months
      ago, suggestive of Hampton's hump. The D-dimer level was raised. Computed
      tomography pulmonary angiography confirmed the diagnosis of pulmonary embolism in
      a right lower lobe segmental branch, with adjacent collapsed lung, consistent
      with lung infarction. The patient was started on heparin injection with
      significant relief of his symptoms. The clinical and imaging features of
      pulmonary embolism are described, with emphasis on the historical radiographic
      signs and the current dual-energy computed tomography innovations.

PMID- 24862754
TI  - Does ageing Singapore need an electronic database of hip fracture patients? The
      value and role of a National Joint Registry and an electronic database of
      intertrochanteric and femoral neck fractures.

PMID- 24862752
TI  - Vitamin D deficiency remains prevalent despite increased laboratory testing in
      New South Wales, Australia.
AB  - INTRODUCTION: The aim of the present study was to assess the prevalence of
      vitamin D deficiency and toxicity, the frequency of 25-hydroxyvitamin D (25[OH]D)
      testing, and 25(OH)D variations with respect to patient gender, patient age and
      season in New South Wales, Australia. METHODS: A retrospective analysis of
      pathology records was performed to ascertain patient age, patient gender, sample
      collection date, plasma or serum 25(OH)D levels, calcium and parathyroid hormone
      (PTH) levels, and test numbers between 2001 and 2010. Linear regression with
      Bonferroni correction was used to calculate and compare age-adjusted mean 25(OH)D
      levels. Relationships of 25(OH)D with PTH and calcium were tested using
      Spearman's rank correlation. RESULTS: 25(OH)D testing increased by 730% over the
      ten-year study period. In 2010, many men (33%) and women (40%) were, to some
      degree, vitamin D deficient (<= 50 nmol/L). Vitamin D toxicity was rare, with
      only one instance noted. 25(OH)D levels correlated positively with calcium and
      negatively with PTH levels. 25(OH)D levels decreased with age. In 2010, 25(OH)D
      levels were highest in February and lowest in September/October. Cyclical
      variation was observed for 25(OH)D levels between 2006 and 2010. CONCLUSION: We
      found that vitamin D deficiency was prevalent in both men and women, with a
      higher prevalence in the latter, despite the substantial increased demand for
      25(OH)D testing in our population over the decade. Vitamin D deficiency was
      associated with elevated PTH levels. Vitamin D toxicity was rare and only
      observed once during our study period. 25(OH)D levels decreased with age and
      varied with season, with the highest levels observed in late summer and the
      lowest in early spring.

PMID- 24862755
TI  - Cortical bone mineral density in patients with congenital adrenal hyperplasia due
      to 21-hydroxylase deficiency.
AB  - BACKGROUND: Prior studies reveal that bone mineral density (BMD) in congenital
      adrenal hyperplasia (CAH) is mostly in the osteopaenic range and is associated
      with lifetime glucocorticoid dose. The forearm, a measure of cortical bone
      density, has not been evaluated. OBJECTIVE: We aimed to evaluate BMD at various
      sites, including the forearm, and the factors associated with low BMD in CAH
      patients. METHODS: Eighty CAH adults (47 classic, 33 nonclassic) underwent dual
      energy-x-ray absorptiometry and laboratory and clinical evaluation. BMD Z-scores
      at the AP spine, total hip, femoral neck, forearm and whole body were examined in
      relation to phenotype, body mass index, current glucocorticoid dose, average 5
      year glucocorticoid dose, vitamin D, 17-hydroxyprogesterone, androstenedione,
      testosterone, dehydroepiandrosterone and dehydroepiandrosterone sulphate (DHEAS).
      RESULTS: Reduced BMD (T-score <-1 at hip, spine, or forearm) was present in 52%
      and was more common in classic than nonclassic patients (P = 0.005), with the
      greatest difference observed at the forearm (P = 0.01). Patients with classic
      compared to nonclassic CAH, had higher 17-hydroxyprogesterone (P = 0.005), lower
      DHEAS (P = 0.0002) and higher non-traumatic fracture rate (P = 0.0005). In a
      multivariate analysis after adjusting for age, gender, height standard deviation,
      phenotype and cumulative glucocorticoid exposure, higher DHEAS was independently
      associated with higher BMD at the spine, radius and whole body. CONCLUSION:
      Classic CAH patients have lower BMD than nonclassic patients, with the most
      affected area being the forearm. This first study of forearm BMD in CAH patients
      suggests that low DHEAS may be associated with weak cortical bone independent of
      glucocorticoid exposure.

PMID- 24862756
TI  - Resistance to the mTOR inhibitor temsirolimus alters adhesion and migration
      behavior of renal cell carcinoma cells through an integrin alpha5- and integrin
      beta3-dependent mechanism.
AB  - Inhibitors of the mammalian target of rapamycin (mTOR) have improved the
      treatment of renal cell carcinoma (RCC). However, chronic drug exposure may
      trigger resistance, limiting the utility of these agents. The metastatic behavior
      of RCC cells, susceptible (RCC(par)) or resistant (RCC(res)) to the mTOR
      inhibitor temsirolimus, was investigated. Adhesion to vascular endothelium or
      immobilized collagen and fibronectin was quantified. Chemotactic motility was
      evaluated with a modified Boyden chamber assay. Integrin alpha and beta subtype
      receptors were analyzed by flow cytometry and Western blot analysis. The
      physiological relevance of the integrins was then determined by blocking studies
      and small interfering RNA knockdown. Adhesion to endothelial cells and to
      fibronectin (not to collagen) and chemotaxis were enhanced in RCC(res) compared
      to RCC(par). RCC(res) detached from fibronectin and motile activity further
      increased under retreatment with low-dosed temsirolimus. alpha5 integrin was
      diminished inside the cell and at the cell surface, whereas the beta3 subtype was
      reduced intracellularly but elevated at the plasma membrane. In RCC(par),
      blocking alpha5 surface receptors enhanced RCC-collagen but reduced RCC
      fibronectin interaction, whereas the opposite was true for RCC(res). Chemotaxis
      of RCC(par) but not of RCC(res) was strongly diminished by the alpha5 antibody.
      Blocking beta3 significantly lowered chemotaxis with stronger effects on
      RCC(res), compared to RCC(par). Importantly, beta3 knockdown reduced chemotaxis
      of RCC(par) but upregulated the motile behavior of RCC(res). Temsirolimus
      resistance is characterized by quantitative alterations of integrin alpha5 and
      beta3 expression, coupled to functional changes of the integrin molecules, and
      forces a switch from RCC adhesion to RCC migration. 

PMID- 24862757
TI  - Activation of HER3 interferes with antitumor effects of Axl receptor tyrosine
      kinase inhibitors: suggestion of combination therapy.
AB  - The Axl receptor tyrosine kinase (RTK) has been established as a strong candidate
      for targeted therapy of cancer. However, the benefits of targeted therapies are
      limited due to acquired resistance and activation of alternative RTKs. Therefore,
      we asked if cancer cells are able to overcome targeted Axl therapies. Here, we
      demonstrate that inhibition of Axl by short interfering RNA or the tyrosine
      kinase inhibitor (TKI) BMS777607 induces the expression of human epidermal growth
      factor receptor 3 (HER3) and the neuregulin 1(NRG1)-dependent phosphorylation of
      HER3 in MDA-MB231 and Ovcar8 cells. Moreover, analysis of 20 Axl-expressing
      cancer cell lines of different tissue origin indicates a low basal
      phosphorylation of RAC-alpha serine/threonine-protein kinase (AKT) as a general
      requirement for HER3 activation on Axl inhibition. Consequently, phosphorylation
      of AKT arises as an independent biomarker for Axl treatment. Additionally, we
      introduce phosphorylation of HER3 as an independent pharmacodynamic biomarker for
      monitoring of anti-Axl therapy response. Inhibition of cell viability by
      BMS777607 could be rescued by NRG1-dependent activation of HER3, suggesting an
      escape mechanism by tumor microenvironment. The Axl-TKI MPCD84111 simultaneously
      blocked Axl and HER2/3 signaling and thereby prohibited HER3 feedback activation.
      Furthermore, dual inhibition of Axl and HER2/3 using BMS777607 and lapatinib led
      to a significant inhibition of cell viability in Axl-expressing MDA-MB231 and
      Ovcar8 cells. Therefore, we conclude that, in patient cohorts with expression of
      Axl and low basal activity of AKT, a combined inhibition of Axl and HER2/3 kinase
      would be beneficial to overcome acquired resistance to Axl-targeted therapies. 

PMID- 24862759
TI  - Prolactin-induced protein is required for cell cycle progression in breast
      cancer.
AB  - Prolactin-induced protein (PIP) is expressed in the majority of breast cancers
      and is used for the diagnostic evaluation of this disease as a characteristic
      biomarker; however, the molecular mechanisms of PIP function in breast cancer
      have remained largely unknown. In this study, we carried out a comprehensive
      investigation of PIP function using PIP silencing in a broad group of breast
      cancer cell lines, analysis of expression microarray data, proteomic analysis
      using mass spectrometry, and biomarker studies on breast tumors. We demonstrated
      that PIP is required for the progression through G1 phase, mitosis, and
      cytokinesis in luminal A, luminal B, and molecular apocrine breast cancer cells.
      In addition, PIP expression is associated with a transcriptional signature
      enriched with cell cycle genes and regulates key genes in this process including
      cyclin D1, cyclin B1, BUB1, and forkhead box M1 (FOXM1). It is notable that
      defects in mitotic transition and cytokinesis following PIP silencing are
      accompanied by an increase in aneuploidy of breast cancer cells. Importantly, we
      have identified novel PIP-binding partners in breast cancer and shown that PIP
      binds to beta-tubulin and is necessary for microtubule polymerization.
      Furthermore, PIP interacts with actin-binding proteins including Arp2/3 and is
      needed for inside-out activation of integrin-beta1 mediated through talin. This
      study suggests that PIP is required for cell cycle progression in breast cancer
      and provides a rationale for exploring PIP inhibition as a therapeutic approach
      in breast cancer that can potentially target microtubule polymerization. 

PMID- 24862758
TI  - Antitumor immunity induced after alpha irradiation.
AB  - Radioimmunotherapy (RIT) is a therapeutic modality that allows delivering of
      ionizing radiation directly to targeted cancer cells. Conventional RIT uses beta
      emitting radioisotopes, but recently, a growing interest has emerged for the
      clinical development of alpha particles. alpha emitters are ideal for killing
      isolated or small clusters of tumor cells, thanks to their specific
      characteristics (high linear energy transfer and short path in the tissue), and
      their effect is less dependent on dose rate, tissue oxygenation, or cell cycle
      status than gamma and X rays. Several studies have been performed to describe
      alpha emitter radiobiology and cell death mechanisms induced after alpha
      irradiation. But so far, no investigation has been undertaken to analyze the
      impact of alpha particles on the immune system, when several studies have shown
      that external irradiation, using gamma and X rays, can foster an antitumor immune
      response. Therefore, we decided to evaluate the immunogenicity of murine
      adenocarcinoma MC-38 after bismuth-213 ((213)Bi) irradiation using a vaccination
      approach. In vivo studies performed in immunocompetent C57Bl/6 mice induced a
      protective antitumor response that is mediated by tumor-specific T cells. The
      molecular mechanisms potentially involved in the activation of adaptative
      immunity were also investigated by in vitro studies. We observed that (213)Bi
      treated MC-38 cells release "danger signals" and activate dendritic cells. Our
      results demonstrate that alpha irradiation can stimulate adaptive immunity,
      elicits an efficient antitumor protection, and therefore is an immunogenic cell
      death inducer, which provides an attractive complement to its direct cytolytic
      effect on tumor cells. 

PMID- 24862760
TI  - VEGFR3 inhibition chemosensitizes ovarian cancer stemlike cells through down
      regulation of BRCA1 and BRCA2.
AB  - In ovarian cancer, loss of BRCA gene expression in tumors is associated with
      improved response to chemotherapy and increased survival. A means to
      pharmacologically downregulate BRCA gene expression could improve the outcomes of
      patients with BRCA wild-type tumors. We report that vascular endothelial growth
      factor receptor 3 (VEGFR3) inhibition in ovarian cancer cells is associated with
      decreased levels of both BRCA1 and BRCA2. Inhibition of VEGFR3 in ovarian tumor
      cells was associated with growth arrest. CD133(+) ovarian cancer stemlike cells
      were preferentially susceptible to VEGFR3-mediated growth inhibition. VEGFR3
      inhibition-mediated down-regulation of BRCA gene expression reversed chemotherapy
      resistance and restored chemosensitivity in resistant cell lines in which a BRCA2
      mutation had reverted to wild type. Finally, we demonstrate that tumor-associated
      macrophages are a primary source of VEGF-C in the tumor microenvironment. Our
      studies suggest that VEGFR3 inhibition may be a pharmacologic means to
      downregulate BRCA genes and improve the outcomes of patients with BRCA wild-type
      tumors. 

PMID- 24862761
TI  - Mechanisms of buffer therapy resistance.
AB  - Many studies have shown that the acidity of solid tumors contributes to local
      invasion and metastasis. Oral pH buffers can specifically neutralize the acidic
      pH of tumors and reduce the incidence of local invasion and metastatic formation
      in multiple murine models. However, this effect is not universal as we have
      previously observed that metastasis is not inhibited by buffers in some tumor
      models, regardless of buffer used. B16-F10 (murine melanoma), LL/2 (murine lung)
      and HCT116 (human colon) tumors are resistant to treatment with lysine buffer
      therapy, whereas metastasis is potently inhibited by lysine buffers in MDA-MB-231
      (human breast) and PC3M (human prostate) tumors. In the current work, we
      confirmed that sensitive cells utilized a pH-dependent mechanism for successful
      metastasis supported by a highly glycolytic phenotype that acidifies the local
      tumor microenvironment resulting in morphological changes. In contrast, buffer
      resistant cell lines exhibited a pH-independent metastatic mechanism involving
      constitutive secretion of matrix degrading proteases without elevated glycolysis.
      These results have identified two distinct mechanisms of experimental metastasis,
      one of which is pH-dependent (buffer therapy sensitive cells) and one which is pH
      independent (buffer therapy resistant cells). Further characterization of these
      models has potential for therapeutic benefit. 

PMID- 24862762
TI  - NHERF1/EBP50 controls morphogenesis of 3D colonic glands by stabilizing PTEN and
      ezrin-radixin-moesin proteins at the apical membrane.
AB  - Na(+)/H(+) exchanger 3 regulating factor 1/ezrin-radixin-moesin (ERM)-binding
      phosphoprotein 50 (NHERF1/EBP50), an adaptor molecule that interacts with the ERM
      neurofibromatosis type 2 family of cytoskeletal proteins through its ERM-binding
      region and with phosphatase and tensin homolog (PTEN) and beta-catenin through
      its PDZ domains, has been recently implicated in the progression of various human
      malignancies, including colorectal cancer (CRC). We report here that NHERF1
      controls gland morphogenesis, as demonstrated in three-dimensional (3D) human
      intestinal glands developing from a single nonpolarized cell. Starting from the
      early two-cell developmental stage, NHERF1 concentrates at the cellular interface
      in a central membrane disc that marks the apical pole delimiting the forming
      lumen. NHERF1 depletion leads to severe disruption of the apical-basal polarity,
      with formation of enlarged and distorted cell spheroids devoid of a central
      lumen. This characteristic and the increased number of mitoses in NHERF1-depleted
      spheroids, including multipolar ones, mimic high-grade dysplasia lesions observed
      in CRC progression. NHERF1 ERM-binding or PDZ-domain mutants fail to localize
      apically and impair gland formation most likely by outcompeting endogenous
      ligands, with the latter mutant completely aborting gland development.
      Examination of NHERF1 ligands showed that even if both ezrin and moesin
      colocalized with NHERF1 at the apical membrane, moesin but not ezrin depletion
      disrupted morphogenesis similarly to NHERF1. NHERF1 depletion resulted also in
      membrane displacement of PTEN and nuclear translocation of beta-catenin, events
      contributing to polarity loss and increased proliferation. These findings reveal
      an essential role of NHERF1 in epithelial morphogenesis and polarity and validate
      this 3D system for modeling the molecular changes observed in CRC. 

PMID- 24862764
TI  - Randomized comparison trial of balance training by using exergaming and
      conventional weight-shift therapy in patients with chronic stroke.
AB  - OBJECTIVE: To compare the effects of exergaming with conventional weight-shift
      training on balance function in patients with chronic stroke. DESIGN: Single
      blind randomized controlled trial. SETTING: Medical center. PARTICIPANTS:
      Patients (N=30) with chronic stroke and balance deficits. INTERVENTIONS: Twelve
      weeks of Wii Fit training or conventional weight-shift training. MAIN OUTCOME
      MEASURES: Static balance was assessed using posturography. We recorded the
      stability index and percentage of weight bearing on the affected leg in 8
      positions. We also used the timed Up and Go and forward reach tests for dynamic
      balance evaluation, Falls Efficacy Scale-International for fear of falling
      assessment, and Physical Activity Enjoyment Scale for estimating the enjoyment of
      training. RESULTS: The exergaming group showed more improvement in stability
      index than the control group in head straight with eyes open while standing on a
      foam surface, eyes closed while standing on a solid surface with head turned 30
      degrees  to the left, and eyes closed while standing on a solid surface with head
      turned up positions (time-group interaction P=.02, .04, and .03, respectively);
      however, the effects were not maintained. At 3-month follow-up, the control group
      showed more improvement in weight-bearing symmetry in the head straight with eyes
      open while standing on a solid surface position than the exergaming group (time
      group interaction P=.03). Both groups showed improvement in the timed Up and Go
      test, forward reach test, and fear of falling. The improvement in fear of falling
      was not maintained. The exergaming group enjoyed training more than the control
      group (P=.03). CONCLUSIONS: Exergaming is enjoyable and effective for patients
      with chronic stroke.

PMID- 24862763
TI  - Short-term effect of spinal manipulation on pain perception, spinal mobility, and
      full height recovery in male subjects with degenerative disk disease: a
      randomized controlled trial.
AB  - OBJECTIVE: To evaluate the short-term effect on spinal mobility, pain perception,
      neural mechanosensitivity, and full height recovery after high-velocity, low
      amplitude (HVLA) spinal manipulation (SM) in the lumbosacral joint (L5-S1).
      DESIGN: Randomized, double-blind, controlled clinical trial with evaluations at
      baseline and after intervention. SETTING: University-based physical therapy
      research clinic. PARTICIPANTS: Men (N=40; mean age +/- SD, 38 +/- 9.14 y) with
      diagnosed degenerative lumbar disease at L5-S1 were randomly divided into 2
      groups: a treatment group (TG) (n=20; mean age +/- SD, 39 +/- 9.12 y) and a
      control group (CG) (n=20; mean age +/- SD, 37 +/- 9.31 y). All participants
      completed the intervention and follow-up evaluations. INTERVENTIONS: A single L5
      S1 SM technique (pull-move) was performed in the TG, whereas the CG received a
      single placebo intervention. MAIN OUTCOME MEASURES: Measures included assessing
      the subject's height using a stadiometer. The secondary outcome measures included
      perceived low back pain, evaluated using a visual analog scale; neural
      mechanosensitivity, as assessed using the passive straight-leg raise (SLR) test;
      and amount of spinal mobility in flexion, as measured using the finger-to-floor
      distance (FFD) test. RESULTS: The intragroup comparison indicated a significant
      improvement in all variables in the TG (P<.001). There were no changes in the CG,
      except for the FFD test (P=.008). In the between-group comparison of the mean
      differences from pre- to postintervention, there was statistical significance for
      all cases (P<.001). CONCLUSIONS: An HVLA SM in the lumbosacral joint performed on
      men with degenerative disk disease immediately improves self-perceived pain,
      spinal mobility in flexion, hip flexion during the passive SLR test, and
      subjects' full height. Future studies should include women and should evaluate
      the long-term results.

PMID- 24862766
TI  - Eye protection in professional hockey.

PMID- 24862765
TI  - English cross-cultural translation and validation of the neuromuscular score: a
      system for motor function classification in patients with neuromuscular diseases.
AB  - OBJECTIVE: To develop and validate an English version of the Neuromuscular (NM)
      Score, a classification for patients with NM diseases in each of the 3 motor
      function domains: D1, standing and transfers; D2, axial and proximal motor
      function; and D3, distal motor function. DESIGN: Validation survey. SETTING:
      Patients seen at a medical research center between June and September 2013.
      PARTICIPANTS: Consecutive patients (N=42) aged 5 to 19 years with a confirmed or
      suspected diagnosis of congenital muscular dystrophy. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: An English version of the NM-Score was
      developed by a 9-person expert panel that assessed its content validity and
      semantic equivalence. Its concurrent validity was tested against criterion
      standards (Brooke Scale, Motor Function Measure [MFM], activity limitations for
      patients with upper and/or lower limb impairments [ACTIVLIM], Jebsen Test, and
      myometry measurements). Informant agreement between patient/caregiver (P/C)
      reported and medical doctor (MD)-reported NM scores was measured by weighted
      kappa. RESULTS: Significant correlation coefficients were found between NM scores
      and criterion standards. The highest correlations were found between NM-score D1
      and MFM score D1 (rho=-.944, P<.0001), ACTIVLIM (rho=-.895, P<.0001), and hip
      abduction strength by myometry (rho=-.811, P<.0001). Informant agreement between
      P/C-reported and MD-reported NM scores was high for D1 (kappa=.801; 95%
      confidence interval [CI], .701-.914) but moderate for D2 (kappa=.592; 95% CI,
      .412-.773) and D3 (kappa=.485; 95% CI, .290-.680). Correlation coefficients
      between the NM scores and the criterion standards did not significantly differ
      between P/C-reported and MD-reported NM scores. CONCLUSIONS: Patients and
      physicians completed the English NM-Score easily and accurately. The English
      version is a reliable and valid instrument that can be used in clinical practice
      and research to describe the functional abilities of patients with NM diseases.

PMID- 24862768
TI  - Optic nerve gray crescent can confound neuroretinal rim interpretation: review of
      the literature.
AB  - The optic nerve gray crescent can be of clinical significance if unrecognized
      during assessment for glaucoma. It has a characteristic appearance of a slate
      gray area of pigmentation within the disc margins and commonly appears along the
      inferotemporal or temporal neuroretinal rim areas. This type of disc rim
      pigmentation can create the impression of neuroretinal rim thinning, and thus
      lead to the misdiagnosis of glaucoma or "glaucoma suspect" with attendant
      implications for overtreatment or unnecessary close monitoring of such patients.
      The gray crescent is more common in African Americans than whites (prevalence
      rate 27% vs 7%) and is bilateral in at least 58% of cases. It has been reported
      in association with Kjer optic atrophy type 1. Suggested causes of the gray
      crescent include an accumulation of melanocytes, or retinal pigment epithelium
      cells partially located in the optic nerve head region if Bruch's membrane
      extends internal to the peripapillary scleral ring. Other causes of pigmentation
      that may resemble gray crescent are conus pigmentosus and variations of
      peripapillary atrophy. When a gray crescent is present, clinicians should
      endeavour to identify the true anatomical disc margins via the scleral lip and,
      if necessary, evaluate the patient further with imaging and visual field studies.

PMID- 24862769
TI  - Impact of visors on eye and orbital injuries in the National Hockey League.
AB  - OBJECTIVE: Eye and orbital injuries are a significant risk to professional hockey
      league players and have resulted in career-ending injuries. The goal of this
      study was to determine the incidence, value lost, mechanism, and effect of visors
      on eye and orbital injuries over the last 10 National Hockey League (NHL)
      seasons: 2002-2003 to 2012-2013. DESIGN: Retrospective case-control study.
      PARTICIPANTS: Participants were 8741 NHL players who had played at least 1 game
      during the last 10 seasons. METHODS: Using The Sports Network (TSN),
      ProSportsTransactions, and the Sporting News Hockey Register, NHL players were
      searched to identify eye and orbital injuries. The mechanism of injury was
      obtained from media reports and direct observation from online videos. The number
      of players wearing visors each year was obtained from The Hockey News annual
      visor survey. RESULTS: A total of 149 eye or orbital injuries over the last 10
      seasons resulted in an overall incidence of 2.48 per 10 000 athlete exposures. A
      total of 1120 missed games led to a lost financial value of more than $33
      million. Visor use among players grew from 32% in 2002-2003 to 73% in 2012-2013,
      and there was a significantly increased risk for having an eye or orbital injury
      when a visor was not worn (OR 4.23, 95% CI 2.84-6.30). Most injuries were a
      result of being hit by a deflected or direct puck (37%) followed by being struck
      by a high stick (28%). Players who did not wear a visor were found to be involved
      in more fights, hits, and penalty minutes (p < 0.001). CONCLUSIONS: Eye and
      orbital injuries are mostly accidental in nature and represent a significant risk
      and cost to the NHL and its players. Eye and orbital injuries are significantly
      more likely in players who do not wear visors.

PMID- 24862770
TI  - Can an inexperienced observer accurately plot disc contours using Heidelberg
      retinal Tomograph?
AB  - OBJECTIVE: To examine the reliability of inexperienced observers in plotting
      optic disc contours on Heidelberg retinal tomography images before and after
      training. DESIGN: Observational study. PARTICIPANTS: One hundred eyes that were
      randomly selected from the Singapore Indian Eye Study. METHODS: Both eyes of
      subjects were imaged with Heidelberg Retina Tomograph 3 (HRT-3; Heidelberg
      Engineering, Heidelberg, Germany). Optic disc contours were plotted on the same
      images by 2 new observers on 2 separate occasions, before and after 2-hour
      standardized training on the skills and tools available to accurately identify
      and delineate optic disc contours. These plottings were compared with an
      experienced, trained glaucoma expert (gold standard). Agreement and variability
      were analyzed by interclass correlation tests and Bland-Altman plots. RESULTS: A
      total of 182 images (18 excluded because of poor quality) from 89 Indian subjects
      were included. The mean age was 53.27 +/- 7.25 years and 54.8% were male. There
      was moderate-to-high agreement between pretraining (both new observers) and
      experienced observer's results (interclass correlation values range, 0.76-0.99).
      The interclass correlation improved for all the HRT-3 parameters after the 2 new
      observers were adequately trained. Comparing the interclass correlation values
      before and after training, the differences for mean retinal nerve fibre layer
      thickness for Observer 1 and all the HRT-3 parameters for Observer 2 were
      statistically significant. CONCLUSIONS: This study shows that it is easy to train
      a new inexperienced observer to plot optic disc contours on HRT images, which
      translates into improved and acceptable interobserver variability and agreement.

PMID- 24862771
TI  - Subretinal fluid drainage via original retinal breaks for rhegmatogenous retinal
      detachment.
AB  - OBJECTIVE: To evaluate the outcome of vitrectomy using only original retinal
      breaks for subretinal fluid (SRF) drainage during the repair of primary
      rhegmatogenous retinal detachment (RRD). DESIGN: A retrospective consecutive
      interventional case series. PARTICIPANTS: A consecutive series of 112 eyes of 112
      patients. METHODS: Patients underwent 23-gauge vitrectomy without the use of
      posterior retinotomy and perfluorocarbon liquids for uncomplicated primary RRD at
      Osaka City University Hospital between September 2007 and March 2011. Exclusion
      criteria included eyes with giant retinal tears, grade C2 or worse proliferative
      vitreoretinopathy (PVR), ocular trauma, and the presence of other vitreoretinal
      diseases. RESULTS: Single-operation success rate was 92.9%, whereas final
      anatomical success rate was 100%. Median visual acuity improved significantly
      from the preoperative logMAR of 0.51 +/- 0.78 to the postoperative logMAR of 0.03
      +/- 0.26 (p < 0.01). No significant differences were observed for the single
      operation success rate between the 62 eyes (95.2%) in which some SRF remained at
      the end of the operation and the rest of the 50 eyes (90.0%, p = 1.000) in which
      the SRF had been completely aspirated. Complications included transient
      intraocular pressure rise (12 eyes, 10.7%), epiretinal membrane (5 eyes, 4.5%),
      and PVR (1 eye, 0.9%). Ocular hypotony and endophthalmitis were not observed.
      CONCLUSIONS: Uncomplicated primary RRD can be successfully repaired by performing
      vitrectomy using only the original retinal breaks for SRF drainage. In addition,
      successful outcomes are not dependent on achieving complete reattachment of the
      retina throughout the fundus.

PMID- 24862772
TI  - Survey of intravitreal injection techniques and treatment protocols among retina
      specialists in Canada.
AB  - OBJECTIVE: To describe intravitreal injection (IVI) techniques and treatment
      protocols by retina specialists in Canada from August 1, 2012, to October 1,
      2012. DESIGN: Cross-sectional survey. PARTICIPANTS: All fellowship-trained retina
      specialists across Canada, as identified from the Canadian Ophthalmological
      Society directory and the Canadian Retina and Vitreous Society directory.
      METHODS: An anonymous 28-question survey was sent to 125 retina specialists
      across Canada by email. Reminder letters were sent by email, mail, and fax as
      necessary. RESULTS: A total of 75 (63%) retina specialists responded to the
      survey. Most IVIs were performed in the office. Most surgeons did not use gloves
      (61%), sterile draping (91%), or surgical mask (71%). Antisepsis was used on
      conjunctiva by 100% and on periocular skin by 48%. Nearly all specialists used a
      sterile lid speculum (91%). Common anaesthetics included topical proparacaine or
      lidocaine drops (90%), topical lidocaine gel (25%), topical pledget (23%), and
      subconjunctival lidocaine injections (23%). Most (83%) dilate the pupil before
      IVI. Prophylactic topical antibiotics were used by 43%; 50% of these were started
      immediately after IVI. Injection location was estimated by visualization by 45%.
      A majority (63%) inject inferotemporally. Anterior chamber paracentesis was
      performed routinely by 5%. Optic nerve perfusion was formally assessed by 48%.
      The most common treatment protocol for age-related macular degeneration was treat
      and extend. For both diabetic and retinal vein occlusion-related macular edema,
      the most common protocol was 3 initial monthly injections with PRN follow-up.
      CONCLUSIONS: A wide variety of IVI practice patterns exist in terms of aseptic
      technique, anaesthetics, prophylactic antibiotics, postinjection monitoring, and
      treatment protocol.

PMID- 24862773
TI  - Predicting 1-month response of macular edema to intravitreal bevacizumab from 1
      hour response.
AB  - OBJECTIVE: To evaluate the clinical significance of the change in central macular
      thickness (CMT) measured 1 h after intravitreal bevacizumab injection (IVB) for
      macular edema (ME) secondary to diabetic retinopathy or retinal vein occlusion
      (RVO). DESIGN: Retrospective case series. PARTICIPANTS: Thirty eyes with ME
      treated with IVB. METHODS: A single IVB (1.25 mg/0.5 mL) was administered in 14
      eyes with diabetic macular edema (DME) and 16 eyes with ME secondary to RVO. CMT
      was measured using spectral-domain optical coherence tomography before injection
      and again 1 hour and 1 month after injection. RESULTS: Statistically significant
      CMT reduction was observed at both time points. CMT declined from 542.3 +/- 127.7
      um at baseline to 516.9 +/- 123.4 um 1 hour after injection (p < 0.001) and to
      345.5 +/- 110.0 um at 1 month after injection (p < 0.001). The reduction in CMT 1
      hour after injection was significantly correlated with the reduction in CMT
      observed at 1 month after injection, with respect to both absolute (r = 0.515, p
      = 0.004) and relative changes (r = 0.454, p = 0.012). The 15 eyes that had larger
      1-hour CMT reductions also showed larger 1-month CMT reductions (242.9 +/- 133.8
      um and 43.4% +/- 16.5%) when compared with 15 eyes with smaller 1-hour CMT
      reductions (148 +/- 130.6 um and 25.0% +/- 18.3%). This trend was the same for
      absolute and relative changes (p = 0.037 and 0.008). CONCLUSIONS: The 1-month
      response of ME to IVB can be predicted by checking CMT 1 hour after injection.

PMID- 24862774
TI  - Long-term results of fluocinolone acetonide intravitreal implant in Behcet
      intractable posterior uveitis.
AB  - OBJECTIVE: To evaluate the long-term efficacy and safety of the fluocinolone
      acetonide intravitreal implant in patients with Behcet disease with intractable
      noninfectious posterior uveitis. DESIGN: Consecutive retrospective analysis.
      PARTICIPANTS: Eight eyes from 7 patients with Behcet uveitis who did not respond
      successfully to conventional treatment with topical and systemic steroids and/or
      systemic steroid-sparing agents were studied. METHODS: We performed a chart
      review of patients who were treated with a 0.59-mg fluocinolone acetonide
      intravitreal implant at a single centre from September 2007 through June 2009.
      Snellen visual acuity, control of inflammation, and the development of
      complications such as infection or uncontrollable intraocular pressure (IOP)
      elevation were evaluated. RESULTS: Mean age at implant placement was 35.3 (range
      17-42) years. Mean follow-up duration was 47.8 (range 39.5-57.6) months.
      Postoperative visual acuity improved by more than 3 lines in 6 eyes (75%). Five
      patients were able to discontinue all systemic medications. Six eyes (75%)
      exhibited postoperative IOP spikes of more than 30 mm Hg. Five patients required
      glaucoma shunting surgery postoperatively for IOP control. The single phakic eye
      developed a visually significant posterior subcapsular lens opacification that
      required cataract extraction. There was 1 case of postoperative cytomegalovirus
      endothelitis. Infection was controlled with oral valganciclovir and topical
      antibiotic medication, and the patient did not require implant removal.
      CONCLUSIONS: The fluocinolone implant is effective in the control of intractable
      inflammation in Behcet uveitis. Elevation of IOP remains a major potential
      complication, and the possibility of infection should be considered.

PMID- 24862776
TI  - Geographic distribution of ophthalmologists in Ontario: a 10-year review.
AB  - OBJECTIVE: Previous studies have shown that access to appropriate care is lacking
      in low-income and rural areas. The goal of this study was to assess the
      geographic variation in the number of ophthalmologists in Ontario from the 2000
      to 2010 fiscal years. DESIGN: Population-based analysis of the geographic
      distribution of Ontario ophthalmologists. PARTICIPANTS: All ophthalmologists who
      held an Ontario license and received payment through the Ontario Health Insurance
      Plan. METHODS: Demographic information was obtained through Intellihealth
      Ontario's Medical Service Provider data source. Ontario counties were stratified
      into low-population (<100000), medium-population (100000-400000), and large
      population (>400000) groups. RESULTS: The ratio of ophthalmologists to population
      was greatest in low-population counties in 2000 (1:65601) and increased further
      in 2010 (1:75434). Only medium-sized counties saw an improvement in the
      ophthalmologist-to-population ratio over the study period. There was no
      statistical difference in the number of ophthalmologists per 100000 population
      between small, medium, and large counties. Counties with an ophthalmology
      residency program had a significantly higher number of ophthalmologists per
      population compared with those without one (1:18162 vs 1:44245). CONCLUSIONS:
      Geographic disparities exist in the distribution of ophthalmologists in Ontario.
      The highest ratios of ophthalmologists to population are found in areas with an
      ophthalmology residency program. New strategies are needed to improve the overall
      numbers and distribution of ophthalmologists to meet the demands of the aging
      population and reduce the burden of vision loss in Canada.

PMID- 24862775
TI  - Intravitreal triamcinolone acetonide as an adjuvant in the management of acute
      retinal necrosis.
AB  - OBJECTIVE: To determine the role of intravitreal triamcinolone acetonide (IVTA)
      as an adjuvant in the management of acute retinal necrosis (ARN). DESIGN:
      Interventional case series. PARTICIPANTS: Four eyes of 4 patients diagnosed with
      ARN were studied. METHODS: This pilot case series included 4 patients who
      presented with clinical features suggestive of ARN. IVTA was injected 1 to 2
      weeks after initiation of antiviral therapy and concurrent usage of oral
      corticosteroids. The disease course and clinical outcome were observed. The
      patients received additional treatment depending on the sequelae of ARN. RESULTS:
      Signs of reduction in vitritis and resolution of retinitis were observed as early
      as 1 week after IVTA was administered. In all 4 patients, inflammation promptly
      resolved with no untoward effects like raised intraocular pressure or worsening
      of the retinitis. A final visual acuity of 20/40 or better was achieved in 3 of 4
      patients after appropriate treatment of ARN-related complications. CONCLUSIONS:
      Intravitreal triamcinolone under antiviral cover could be a useful adjunct to
      systemic steroids in the treatment of ARN.

PMID- 24862777
TI  - Comparison of lifestyle and practice patterns between male and female Canadian
      ophthalmologists.
AB  - OBJECTIVE: To identify sex differences in lifestyle and practice patterns of
      Canadian ophthalmologists. DESIGN: Web-based national survey. PARTICIPANTS:
      Members of the Canadian Ophthalmological Society. METHODS: A 48-item
      questionnaire was sent electronically. Analysis of results was completed using
      chi(2) and Fisher's exact tests where appropriate. RESULTS: Of 385 respondents
      (30%), 102 were female and 283 male. Several statistically significant
      differences exist in lifestyle and practice patterns. Fifty-one percent of
      females operate less than 2 days per month as compared with 36% of males (p =
      0.01) despite similar clinical hours. No statistically significant differences
      were found in other practice pattern parameters including laser refractive
      surgery, hospital affiliation, university appointment/rank, and number of peer
      review publications. Ninety percent of males and 81% of females report having >=1
      children, but males report greater number of children (p < 0.001). Females are
      commonly the primary caregiver, whereas males report their partner as primary
      caregiver (p < 0.001). Fifty-two percent of females are unhappy with the amount
      of parental leave (p < 0.001). Fifty-one percent of females believe that
      childbearing slowed or markedly slowed career progress, as compared with 15% of
      males (p < 0.001). Both female (83%) and male (87%) ophthalmologists report high
      career satisfaction (p = 0.43). CONCLUSIONS: Differences in practice patterns
      between males and females in our analysis surround surgical time, with no
      difference seen in other practice patterns or academic achievements. Differences
      in family patterns surround household and childrearing duties. Despite
      differences, both males and females report high satisfaction across several
      professional and personal parameters. Compared with previous studies, this
      suggests a change in practice patterns over time.

PMID- 24862779
TI  - Changes in corneal astigmatism among patients with visually significant cataract.
AB  - OBJECTIVE: To determine the prevalence of corneal astigmatism, changes in
      astigmatism, and biometry measurements with age and to correlate fellow eye
      measurements of patients undergoing cataract surgery. DESIGN: Prospective,
      observational study. PARTICIPANTS: 3498 eyes of 1814 patients undergoing cataract
      surgery. METHODS: Setting was a single center teaching hospital. Preoperative
      biometry data measured by partial coherence interferometry (IOLMaster; Carl Zeiss
      Meditec, Jena, Germany) were collected and analyzed. RESULTS: Mean age of the
      cohort was 74.52 +/- 10.23 years. Mean corneal astigmatism was 1.04 +/- 0.78 D OD
      and 1.04 +/- 0.79 D OS. About 19.7% and 4.9% of eyes had corneal astigmatism
      greater than 1.5 and 2.5 D, respectively. The prevalence of against-the-rule
      astigmatism significantly increased with age bilaterally. Paired fellow eye
      analysis found a positive correlation for corneal astigmatism, axial length,
      anterior chamber depth, and white-to-white distance (p < 0.001). About 33.33% of
      right eyes with corneal astigmatism greater than 2.5 D had more than 2.5 D of
      astigmatism in the fellow eye. This is in comparison with only 1.5% of right eyes
      with corneal astigmatism of less than 1.5 D having corneal astigmatism greater
      than 2.5 D in the fellow eye. CONCLUSIONS: Patients with high corneal astigmatism
      in 1 eye are more likely to have significant astigmatism in the fellow eye. This
      may necessitate the need for bilateral toric intraocular lens (IOL) implantation
      during cataract surgery. Against-the-rule astigmatism should be treated more
      aggressively during cataract surgery, because this is likely to worsen with age.
      Such information is useful when calculating toric IOL power at the time of
      surgery.

PMID- 24862778
TI  - Aging and feminization of the physician workforce in Canada: comparing
      ophthalmologists to all other physicians.
AB  - OBJECTIVE: To describe the changing demographic of ophthalmologists compared with
      all other physicians in Canada. DESIGN: Cross-sectional study. PARTICIPANTS:
      Ophthalmologists and all other physicians listed in the Canadian Institute for
      Health Information (CIHI) and Canadian Medical Association (CMA) databases.
      METHODS: The CIHI database was used to determine the yearly number, mean age, and
      sex of licensed ophthalmologists and all other physicians in Canada from 1970 to
      2011. The CMA database was used to determine the 2011 provincial sex distribution
      of ophthalmologists. RESULTS: The mean age of physicians is increasing over time;
      however, the mean age of ophthalmologists has been greater than all other
      physicians since 1972 by a mean of 2.4 years. In 2011, the mean age of all
      ophthalmologists was 53.1 years compared with 50.4 years for all other
      physicians. The yearly mean age of female ophthalmologists (48 in 2011) and all
      other female physicians (46.1 in 2011) was younger than males. The proportion of
      female ophthalmologists has increased from 3.1% to 20.5% from 1970 to 2011. This
      is significantly less than all other specialties where the proportion increased
      from 7.8% to 36.8% (p < 0.001). The proportion of female ophthalmologists varies
      significantly among the provinces from 7.1% in Newfoundland and Labrador to 31.1%
      in Quebec in 2011. CONCLUSIONS: The mean age of all physicians is increasing over
      time with ophthalmologists being, on average, 2.3 years older than other
      physicians. Although the proportion of female physicians is increasing, the rate
      of increase is less in ophthalmology compared with all other physicians and
      varies significantly between provinces.

PMID- 24862780
TI  - First report of keratitis in familial cold autoinflammatory syndrome.
AB  - OBJECTIVE: To report corneal manifestations of familial cold autoinflammatory
      syndrome (FCAS) for the first time. DESIGN: small case series PARTICIPANTS:
      Medical records of three members of a single family were reviewed after obtaining
      institutional review board (IRB) approval and informed consent. METHODS: All
      three members presented with a long history of maculopapular rash after cold
      exposure starting in childhood associated with nausea, low-grade fever, fatigue
      and arthralgia that lasted less than 24 hours. Their ocular manifestations
      consisted of ocular pain, photophobia and keratitis with subsequent stromal
      haziness. RESULTS: Patients underwent systemic therapy with canalinumab (Ilaris).
      They responded very well to repeated injections of Ilaris without side effects.
      CONCLUSIONS: FCAS causes lifelong debilitating effects that restrict patients'
      daily activities. Ilaris is an FDA-approved treatment for this condition and that
      typically results in dramatic improvement in clinical and laboratory measures of
      inflammation, and is well tolerated. Our report is the first small case series of
      FCAS with keratitis that responded to Ilaris beautifully.

PMID- 24862781
TI  - RE: Ultrachopper tip.

PMID- 24862782
TI  - RE: Microperimetry and the diagnosis of antimalarial maculopathy.

PMID- 24862783
TI  - RE: Author reply:.

PMID- 24862784
TI  - Temporal artery enhancement on cranial magnetic resonance imaging.

PMID- 24862786
TI  - Use of a smartphone to estimate anomalous head postures.

PMID- 24862785
TI  - Acute eosinophilic meningitis and orbital inflammation from presumed
      angiostrongyliasis.

PMID- 24862787
TI  - Chronic myelogenous leukemia presenting with bilateral optic disc
      neovascularization.

PMID- 24862788
TI  - Low-vision rehabilitation methods in children: a systematic review.

PMID- 24862790
TI  - Management of late postoperative capsular block syndrome with accumulation of
      Propionibacterium acnes.

PMID- 24862789
TI  - Double-hit vitreoretinal lymphoma.

PMID- 24862791
TI  - Sebaceoma of the eyelid: a rare entity.

PMID- 24862792
TI  - Bilateral choroidal neovascularization associated with basal laminar drusen in a
      31-year-old.

PMID- 24862793
TI  - Novel insights into the antiproliferative effects and synergism of quercetin and
      menadione in human leukemia Jurkat T cells.
AB  - The flavonoid quercetin and menadione (vitamin K3) are known as potent apoptogens
      in human leukemia Jurkat T cells. We explored some underlying mechanisms and the
      potential relevance of the combination quercetin-menadione for clinical
      applications. In acute treatments, quercetin manifested a strong antioxidant
      character, but induced a transient loss of Deltapsim, likely mediated by opening
      of the mitochondrial permeability transition pore. After removal of quercetin,
      persistent mitochondrial hyperpolarization was generated via stimulation of
      respiratory Complex I. In contrast, menadione-induced Deltapsim dissipation was
      only partially and transiently reversed after menadione removal. Results indicate
      that Ca(2+) release is a necessary event in quercetin-induced cell death and that
      the survival response to quercetin is delineated within 1h from exposure.
      Depending on dose, the two agents exhibited either antagonistic or synergistic
      effects in reducing clonogenicity of Jurkat cells. 24-h combinatorial regimens at
      equimolar concentrations of 10-15 MUM, which are compatible with a clinically
      achievable (and safe) scheme, reduced cell viability at efficient rates.
      Altogether, these findings support the idea that the combination quercetin
      menadione could improve the outcome of conventional leukemia therapies, and
      warrant the utility of additional studies to investigate the therapeutic effects
      of this combination in different cellular or animal models for leukemia.

PMID- 24862794
TI  - Case-adjusted bortezomib-based strategy in routine therapy of relapsed/refractory
      multiple myeloma shown to be highly effective--a report by Polish Myeloma Study
      Group.
AB  - The observational study was aimed at evaluating response, survival and toxicity
      of bortezomib-based, case-adjusted regimens in real-life therapy of 708
      relapsed/refractory MM patients. Bortezomib was combined with anthracyclines,
      steroids, thalidomide, alkylators or given in monotherapy. The ORR was 67.9% for
      refractory and 69.9% for relapsed MM. The median PFS was 14 months and OS 57
      months. Patients responding to the therapy had the probability of a 4-year OS at
      67.0%. No toxicity was noted in 33.1% of patients. Severe events (grade 3/4) were
      reported in 35.9% of patients: neurotoxicity (16.7%), neutropenia (9.2%),
      thrombocytopenia (8.5%), and infections (6.5%). Bortezomib-based, case-adjusted
      regimens are in real-life practice effective in salvage therapy offering reliable
      survival with acceptable toxicity for relapsed/refractory MM patients. 

PMID- 24862795
TI  - Peroxiredoxin 2 expression is increased in neutrophils of patients with
      refractory cytopenia with multilineage dysplasia.
AB  - Myelodysplastic syndromes (MDS) are heterogeneous clonal disorders characterized
      by cytopenias that arise due to ineffective haematopoiesis and morphological
      dysplasia and carry an increased risk of incident acute myeloid leukaemia. The
      pathogenesis of marrow dysfunction in MDS is multifactorial and consistent with a
      multistep model and may lead to heterogeneity of MDS. We investigated the
      proteome profile of circulating neutrophils purified from patients with
      refractory cytopenia with multilineage dysplasia (RCMD) to identify proteins that
      have a role in the pathogenesis. Using 2-dimensional difference gel
      electrophoresis and protein identification by matrix-assisted laser desorption
      ionization time-of-flight mass spectrometry, we found that peroxiredoxin 2
      (PRDX2), a member of the peroxiredoxin family that regulates reactive oxygen
      species, was markedly upregulated in neutrophils of RCMD patients compared to
      healthy donors. Increased PRDX2 expression in the neutrophils of RCMD patients
      was confirmed using quantitative reverse transcription polymerase chain reaction,
      immunoblotting and immunocytochemical analysis. In addition, white blood cell and
      neutrophil counts in RCMD patients correlated inversely with the PRDX2 expression
      of. Oxidative stress is a known factor involved in the pathogenesis of MDS, and
      PRDX2 is associated with tumourigenesis of several solid tumours. Accordingly,
      our results suggest that PRDX2 may perform an important function in the
      pathogeneis of RCMD. 

PMID- 24862796
TI  - Interspecies differences in reaction to a biodegradable subcutaneous tissue
      filler: severe inflammatory granulomatous reaction in the Sinclair minipig.
AB  - Soft tissue filler products have become very popular in recent years, with ever
      increasing medical and aesthetic indications. While generally considered safe,
      the number of reported complications with tissue fillers is growing.
      Nevertheless, there is no specific animal model that is considered as the gold
      standard for assessing safety or efficacy of tissue fillers, and there are very
      little data on interspecies differences in reaction to these products. Here, we
      report on interspecies differences in reaction to a subcutaneous injectable co
      polyester, composed of castor oil and citric acid. Comparison of the
      histopathological local tissue changes following 1-month postimplantation,
      indicated that in rats the reaction consisted of cavities, surrounded by
      relatively thin fibrotic enveloping capsule. In contrast, an unexpected severe
      inflammatory granulomatous reaction was noticed in Sinclair minipigs. To our
      knowledge, this is the first report on significant interspecies differences in
      sensitivity to tissue fillers. It emphasizes the importance of using the
      appropriate animal model for performing preclinical biocompatibility assays for
      biodegradable polymers, tissue fillers, and implanted medical devices in general.
      It also makes the Sinclair minipig subject for scrutiny as an animal model in
      future biocompatibility studies. 

PMID- 24862797
TI  - Regulatory Forum opinion piece: New testing paradigms for reproductive and
      developmental toxicity--the NTP modified one generation study and OECD 443.
AB  - The National Toxicology Program (NTP) has developed a new flexible study design,
      termed the modified one generation (MOG) reproduction study. The MOG study will
      encompass measurements of developmental and reproductive toxicity parameters as
      well as enable the setting of appropriate dose levels for a cancer bioassay
      through evaluation of target organ toxicity that is based on test article
      exposure that starts during gestation. This study design is compared and
      contrasted with the new Organization for Economic Co-operation and Development
      (OECD) 443 test guideline, the extended one generation reproduction study. The
      MOG study has a number of advantages, with a focus on F 1 animals, the generation
      of adequately powered, robust data sets that include both pre and postnatal
      developmental toxicity information, and the measurement of effects on
      reproductive structure and function in the same animals. This new study design
      does not employ the use of internal triggers in the design structure for the use
      of animals already on test and is also consistent with the principles of the
      3R's.

PMID- 24862799
TI  - Contradictions and inequities in medical prevention.

PMID- 24862798
TI  - Inhibitory potential of postnatal treatment with cyclopamine, a hedgehog
      signaling inhibitor, on medulloblastoma development in Ptch1 heterozygous mice.
AB  - Medulloblastomas (MBs) are thought to be derived from granular cell precursors in
      the external granular layer (EGL) of the developing cerebellum. Heterozygous
      patched1 (Ptch1) knockout mice develop MBs that resemble those in humans when the
      sonic hedgehog (Shh) signaling pathway is activated. The present study was
      conducted to evaluate postnatal effects of a Shh signaling inhibitor,
      cyclopamine, on the development of MBs in Ptch1 mice. Ptch1 and wild-type mice
      were treated daily with subcutaneous cyclopamine at 40 mg/kg or vehicle from
      postnatal day (PND) 1 to PND14, and the subsequent development of MBs and
      preneoplastic lesions was examined up to week 12 (W12). Proliferative lesions in
      the cerebellum, MBs, and preneoplastic lesions were only detected in Ptch1 mice.
      Cyclopamine treatment resulted in a statistically significant reduction in the
      incidence and/or area of proliferative lesions at PND14 and 21. The trend of
      decreasing preneoplastic lesions persisted up to W12. At PND7, cyclopamine
      treatment reduced the width and proliferation of the EGL regardless of genotype.
      These results indicate that inhibition of Shh signaling during cerebellar
      development has prolonged inhibitory potential on MB development in Ptch1 mice.
      This inhibitory potential might be related to inhibition of EGL proliferation,
      including preneoplastic MB cells.

PMID- 24862800
TI  - How the concept of race influences medical practice. A reflection based on a
      study about the diagnosis and treatment of upper respiratory tract infections in
      American children.

PMID- 24862801
TI  - Consumption of non-nutritive sweeteners and nutritional status in 10-16 year old
      students.
AB  - INTRODUCTION: The impact of non-nutritive sweeteners (NNS) on energy intake and
      body weight is not clear although they provide no energy compared to sucrose.
      OBJECTIVE: To establish if there are differences in the consumption of NNS as per
      the nutritional status and its association with overweight. POPULATION, MATERIAL
      AND METHODS: Cross-sectional study including 571 male and female students aged 10
      16 years old from the cities of Vina del Mar and Santiago de Chile who were
      administered an adapted food survey using pictures of NNS-containing products;
      nutritional status was assessed and students with overweight and obesity were
      categorized as a the overweight group. RESULTS: Of all surveyed students, 96.6%
      consume NNS on a daily basis. The comparison between the total NNS intake by
      nutritional status showed that male students in the overweight group consume more
      sucralose (p < 0.05) and saccharin (p < 0.01), while the comparison of NNS intake
      per kilogram of body weight showed that NNS consumption was higher in the
      overweight group (p < 0.05). Among female students, the normal weight group
      showed a higher consumption of acesulfame K per kilogram of body weight than the
      overweight group (p < 0.05). No association was observed in the studied sample
      between the overall NNS intake and obesity. CONCLUSION: Of all surveyed students,
      96.6% consume NNS on a daily basis, and no association was found between NNS
      consumption and overweight.

PMID- 24862802
TI  - Adverse social determinants and risk for congenital anomalies.
AB  - INTRODUCTION: Different studies have related familiar and regional adverse social
      conditions to perinatal outcome (neonatal mortality, low birth weight and
      prematurity); however, few studies have studied the effect of poverty on
      congenital anomalies. OBJECTIVE: To assess the hazard ratio of 25 congenital
      anomalies and adverse social determinants as per the socioeconomic level of
      families and regions. POPULATION AND METHODS: Exploratory, case-control study
      using data from the Latin-American Collaborative Study of Congenital
      Malformations (Estudio Colaborativo Latinoamericano de Malformaciones Congenitas,
      ECLAMC). The sample consisted of 3786 live newborn infants with a single
      malformation and 13,344 controls selected among 546,129 births occurred in 39
      hospitals from Argentina in the 1992-2001 period. Both direct and indirect
      (residence) risks (OR) were estimated, together with the interaction between the
      individual and residential socioeconomic levels for each of the 25 congenital
      anomalies. RESULTS: Cleft lip with/without cleft palate (OR= 1.43) and
      ventricular septal defect (OR= 1.38) showed a significantly higher risk in the
      lower socioeconomic level. Low socioeconomic levels were significantly associated
      with a higher frequency of parental sibship (blood relationship); native descent;
      maternal age younger than 19 years old; more than four pregnancies; a low number
      of antenatal care visits; and residence in deprived regions. CONCLUSION: Cleft
      lip with/without cleft palate and ventricular septal defects were significantly
      associated with a lower socioeconomic level. Lack of family planning and
      antenatal care; and exposure to environmental or teratogenic agents may account
      for these findings.

PMID- 24862803
TI  - An online explorative study towards parents' opinions about organ donation: from
      individual decisions to family discussions.
AB  - BACKGROUND: Parental decisions about organ donation by their child are influenced
      by many factors. One of these factors may be a previous discussion under non
      crisis circumstances. The question then arises whether parents have thought about
      this topic for themselves and discussed it with each other or with their child.
      METHODS: An initial exploratory Internet survey to explore these discussions,
      parental opinions about school lessons on donation, the age threshold for a child
      to decide about donation, and determinants that influence these aspects.
      Questionnaire was sent to 14,000 panel members. We selected respondents with
      children younger than 16 years old. RESULTS: Questionnaire response rate was 35%.
      Of all 1146 respondents with children, 84% had discussed the topic with their
      partner and, on average, 46.5% had discussed this with their child aged 10-16
      years old. Religion and educational level of the parents were not related. Sixty
      nine percent of parents were positive towards school lessons. Most of the
      children were allowed to decide for themselves at the age of 15/16 years old.
      CONCLUSION: Family discussions between spouses about donation do occur
      frequently, however, discussion with children can be improved. If desired,
      triggers for beginning these conversations could be provided through public
      information and school education, which would also contribute to health literacy
      on this subject.

PMID- 24862804
TI  - Health-related quality of life in children with chronic conditions lodged at a
      comprehensive accommodation in the City of Buenos Aires.
AB  - INTRODUCTION: The treatment of chronic diseases usually requires a
      multidisciplinary professional training.There are comprehensive accommodations
      that are adapted to the needs of the families that have to stay away from home
      for long periods. OBJECTIVES: To assess the impact of a comprehensive
      accommodation on the health-related quality of life of children with chronic
      conditions seen at a hospital of the City of Buenos Aires compared to children
      lodged at a traditional accommodation and to healthy children. To analyze the
      agreement between children's and caregivers' opinions. Metfeods.Cross-sectional,
      observational study. Group 1: children with chronic conditions lodged at a
      comprehensive accommodation. Group 2: children with chronic conditions lodged at
      a traditional accommodation. Group 3: healthy children. The Argentine version of
      the Kidscreen-52 questionnaire was used. A value of p < 0.05, the effect size
      (ES) > 0.20, and the intraclass correlation coefficient (ICC) > 0.60 were
      considered significant. RESULTS: Two hundred and fifty children/caregiver dyads
      (50 in each chronic group and 150 healthy controls). Mean age: 12.6 years old
      (range: 8-18 years old), 56% were males. The children in Group 1 showed better
      moods and emotions, a better relationship with parents and peers, and a better
      school environment than those in Group 2 (p < 0.05, ES > 0.20). Agreement between
      children's and caregivers' opinion was low, especially in relation to
      psychosocial dimensions (ICC < 0.29). CONCLUSIONS: In spite of their uprooting,
      children with chronic conditions are capable of maintaining a good relationship
      with their parents, a good peer bond and social support, and do not need
      discontinue their education while lodged at a comprehensive accommodation adapted
      to their needs during their stay in the City of Buenos Aires.

PMID- 24862805
TI  - Sleepiness and sleep characteristics in students from an urban district of Lima,
      Peru.
AB  - INTRODUCTION: Sleepiness in students has an impact on their learning, focus and
      memory. Sleepiness is caused by multiple factors. Therefore, our objective was to
      estimate the frequency of sleepiness in Peruvian students and assess its relation
      to lifestyle and sleep habits. METHODS: Cross-sectional study conducted on first
      through fifth year secondary students. The Spanish version of the pediatric
      daytime sleepiness scale (0 to 32 points) was administered and sleep and
      demographic characteristics and harmful habits, among others were investigated.
      Excessive sleepiness was considered as a score higher than 20 points, and its
      association was assessed using raw and adjusted odds ratios. RESULTS: The study
      included 586 students; the average score in the pediatric daytime sleepiness
      scale was 13.0 +/- 5.5; 11.9% of students had excessive sleepiness. Smoking was
      associated with excessive sleepiness, with an adjusted OR of 6.9 (95% CI: 2.9
      17.0); alcohol consumption showed an OR of 4 (95% CI: 1.5-10.5), and practicing
      sports showed an OR of 0.5 (95% CI: 0.3-0.9). Likewise, having a bad sleep
      quality (OR: 5.4; 95% CI: 3.1-9.5) and taking more than 60 minutes to fall asleep
      (OR: 2.5; 95% CI: 1.16.0) were associated with a higher probability of having
      sleepiness. CONCLUSION: Sleepiness was observed in 12% of the studied population,
      and was found to be lower than the rates described in studies with different
      populations. Excessive sleepiness is associated with smoking and frequent alcohol
      consumption, a lower level of sports practice, and bad sleep habits.

PMID- 24862806
TI  - School dysfunction in 5 to 19 year old children with only motor disabilities seen
      at a reference hospital in Argentina.

PMID- 24862807
TI  - Analysis of clinical trials and off-label drug use in hospitalized pediatric
      patients.
AB  - Introduction. The lack of pediatric clinical trials (PCTs) leads to an off-label
      drug use (OLDU) in children. Our objective was to analyze the number and design
      of PCTs and OLDU in children in the past years. Population, material and methods.
      Observational and retrospective study on PCTs and OLDU in children, conducted
      from 2007 to 2012 in a 252-bed children's hospital. The number and design of PCTs
      and OLDU in children were analyzed by year and by characteristics. Results.
      Eighty-seven PCTs and 449 active ingredients corresponding to 1049 drugs
      prescribed to hospitalized children were evaluated.Of these, 117 (26%) were used
      off-label. The number of PCTs increased from 2008 to 2011. In 2011, 52.2% of PCTs
      were non-randomized and uncontrolled studies, and only 39.1% were randomized,
      controlled trials. Of all studied drugs, 77% corresponded to off-label use. OLDU
      in children remained steady throughout the study period. Conclusions. In our
      hospital, the number of pediatric research studies has increased in the past
      years, being non-randomized and uncontrolled studies the most frequent. OLDU in
      children has not changed. 

PMID- 24862808
TI  - The initiation of complementary feeding among Qom indigenous people.
AB  - As of six months of life, breastfeeding no longer covers an infant's energy or
      micronutrient needs, so appropriate complementary feeding should be provided. The
      objective of this study was to assess the time and adequacy for introducing
      complementary feeding in a Qom/Toba population and analyze the sociocultural
      concepts of families regarding complementary feeding. Quantitative and
      qualitative data were collected by participant observation and semistructured
      surveys administered to mothers of 0-2 year old infants. Qom breastfeed their
      infants long term and on demand. Most infants have an adequate nutritional status
      and start complementary feeding at around 6 months old as per the local health
      center and international standards. However, mostly due to socioeconomic factors,
      foods chosen to complement breastfeeding have a relatively scarce nutritional
      value. 

PMID- 24862809
TI  - [Mucopolysaccharidosis type VI: clinical aspects, diagnosis and treatment with
      enzyme replacement therapy].
AB  - Mucopolysaccharidosis VI (MPS VI) is a lysosomal storage disease associated with
      a deficiency or absence of arylsulfatase B leading to the abnormal accumulation
      of dermatan sulfate. MPS VI shows a wide spectrum of symptoms from slowly to
      rapidly progressing forms. The characteristic spectrum includes skeletal
      displasia, coarse facies, cardiomyopathy, pulmonary complications and spinal
      compression. Diagnosis generally requires measurement ofurinary
      glycosaminoglycans and arylsulfatase B enzyme activity in dried blood spot,
      leukocytes or cultured fibroblasts. Enzyme replacement therapy (ERT) with
      galsulfase is now widely available providing improvement in skeletal performance
      and stabilization in pulmonary and cardiac functioning. Spinal involvement does
      not respond to ERT when is present, surgical decompression should be indicated
      early. Prognosis is variable depending on the age of onset and age at initiation
      of ERT. 

PMID- 24862810
TI  - [Parental stress in children undergoing congenital heart surgery].
AB  - The caregivers of children with congenital heart disease undergoing cardiac
      surgery are under stress due to the uncertainty of the surgical outcome and the
      stressful experience of being admitted in an intensive care unit. The current
      review describes the factors associated with parental stress in patients with
      congenital heart disease undergoing cardiac surgery. These factors can be grouped
      into factors related to the patient, the parents, the environment and the
      clinical team. The loss of the parental role, the physical appearance and the
      child's behavior during their stay in the intensive care unit are identified as
      the most powerful sources of stress. An information program to be given to the
      caregivers before cardiac surgery should include all these factors as a central
      part of its contents, should significantly reduce the levels of parental stress
      and must be included in the process of admitting a patient for congenital heart
      surgery. 

PMID- 24862811
TI  - [Collective health checks for children: an experience in Villa Caracol, Bahia
      Blanca].
AB  - The health team in the San Dionisio Health Center developed a device called
      Collective Health Checks for Children (CHCC) to minimize the difficulties arise
      for effective coverage of health checks of children in the neighborhood of Villa
      Caracol, Bahia Blanca. The objectives of the CHCC were to strengthen the sense of
      family responsibility for children's health, conduct a screening of children
      needing urgently health control and strengthen personal living spaces. There were
      five days of CHCC for children 2 to 14 year, 101 children were attended,
      achieving a coverage of 82.11%. Adhesion to the device was achieved in a
      recreational space in the neighborhood, which in turn was associated with healthy
      habits, specifying the sense of family responsibility for the health of children.

PMID- 24862812
TI  - [Consensus on treatment of nephrotic syndrome in childhood].

PMID- 24862813
TI  - [Guidelines of categorization, organization and functioning of the Pediatric
      Intensive Care Units and Pediatric Intermediate Care Units in health care
      facilities: part I: Categorization -Pediatric Intensive Care Unit Level 1].

PMID- 24862814
TI  - [Guideline for diagnosis and treatment of patients with cystic fibrosis: update].

PMID- 24862815
TI  - [Atopic dermatitis: national consensus 2013].

PMID- 24862816
TI  - [What is your diagnosis? Resolution of the case presented in the previous issue.
      Severe complications due to retropharyngeal abscess].

PMID- 24862817
TI  - [Nasolaryngotracheal mucosal leishmaniasis in an adolescent].
AB  - Leishmaniasis is a growing public health problem and it produces a great social
      impact. Laryngeal leishmaniasis without obvious gateway is rare; especially in
      immunocompetent patients. We report a case of laryngeal leishmaniasis with
      tracheal involvement and stenosis on a previously healthy teenager without
      environmental or personal risk factors. 

PMID- 24862819
TI  - Severe phenotype in two half-sibs with Adams Oliver syndrome.
AB  - Adams Oliver syndrome (AOS) is a highly variable entity with terminal transverse
      limb defects (TTLD) and aplasia cutis congenita (ACC) with a wide phenotypic
      spectrum. Several inheritance models have been observed; the most severe
      phenotype has been related to an autosomal recessive (AR) pattern of inheritance.
      OBJECTIVE. To present a family with two half siblings with a severe phenotype of
      Adams Oliver syndrome in which the mother was healthy. CASE REPORT: A 27 year-old
      woman was referred to the Genetics Department. Her previous girl presented
      acrania, constriction rings and terminal transverse limb defects. The present
      girl had occipital encephalocele, large scalp defects, aplasia cutis congenita,
      terminal transverse limb defects and bilateral cleft lip and palate. Autosomal
      dominant inheritance with reduced penetrance or gonadal mosaicism has to be
      considered in Adams Oliver syndrome with severe intracranial anomalies.

PMID- 24862818
TI  - Esophageal dislodgement of an endotracheal tube during nasopharyngeal oxygenation
      in a neonate with Pierre-Robin sequence: a case report.
AB  - Conventional intubation for pulmonary management in children with a difficult
      airway may be very challenging even in skilled hands. Rapid advancements in
      respiratory care have reduced the incidence of difficult tracheal intubation and
      the incidence of complications have decreased accordingly. However, serious
      unexpected complications still occur in some patients today. Herein, we describe
      a syndromic newborn infant with a difficult airway who experienced migration of
      the endotracheal tube into the esophagus after displacement of the tube
      connector. We would like to share our experience and contribute to the literature
      with the presentation of this undesired event. To the best of our knowledge, no
      such complication has been reported in the neonatal literature before. 

PMID- 24862820
TI  - [Bilateral spontaneous pneumothorax as a setting of Langerhans cell
      histiocytosis].
AB  - Pulmonary Langerhans cell histiocytosis is an interstitial lung disease that
      results from the accumulation of specific histiocytic cells in the lung.
      Spontaneous pneumothorax is a recognized feature of pulmonary Langerhans cell
      histiocytosis and results from destruction of lung parenchyma with associated
      cystic changes. We report on a 2-year-old boy with recurrent bilateral
      spontaneous pneumothorax; a computed tomography scan showed marked interstitial
      changes, fibrosis, cystic spaces and bilateral bullae. The diagnosis was
      confirmed by the histology and the immunohistochemistry examination of the
      pulmonary biopsy with CD1 and S100 positive antibodies. The child was treated
      with prednisone and etoposide, and had a good clinical response and favorable
      changes in the second thoracic CT scan. 

PMID- 24862821
TI  - [The role of physical examination in establishing the diagnosis of pneumonia].

PMID- 24862824
TI  - [Cutaneous tuberculosis: case report].
AB  - Cutaneous tuberculosis is a chronic infectious disease caused by Mycobacterium
      tuberculosis. It is not very frequent and particularly difficult to diagnose. It
      incidence ranges between 1.5 and 4% of all extrapulmonary tuberculosis, according
      to bibliography. The clinic presentations depend on the arrival via of the
      bacillus to the skin, the patient's immune state and the environment. We show a
      cutaneous tuberculosis on a child with chronic dermatologic lesions, with torpid
      evolution, without response to treatments; the skin biopsy showed caseous
      granulomas. The aim is to show a patient with an infrequent clinic presentation
      of this disease, to emphasize the importance of an early recognition and
      treatment, avoiding the appearance of complications and sequels.

PMID- 24862825
TI  - [Gait analysis in spinal cord injured population: a case report].
AB  - Gait analysis in spinal cord injured population is a very effective current
      diagnostic tool to prescribe an appropriate rehabilitation treatment. Spinal cord
      injury in childhood is a rare condition, with lower incidence than in adulthood.
      It carries particular importance due to physical, emotional, social, family and
      economic consequences. A case of a man with cervical level spinal cord injury has
      been described; for his treatment it is necessary the use of botulinum toxin. It
      was made a pre and post-treatment study to test the effectiveness of this
      therapy. This clinical case, along with a literature review, will help clinicians
      in the best treatment of this pathology. 

PMID- 24862826
TI  - Chronic sensitivity of white sturgeon (Acipenser transmontanus) and rainbow trout
      (Oncorhynchus mykiss) to cadmium, copper, lead, or zinc in laboratory water-only
      exposures.
AB  - Chronic toxicity of cadmium, copper, lead, or zinc to white sturgeon (Acipenser
      transmontanus) and rainbow trout (Oncorhynchus mykiss) was evaluated in water
      only exposures started with newly hatched larvae or approximately 1-mo-old
      juveniles. The 20% effect concentration (EC20) for cadmium from the sturgeon
      tests was higher than the EC20 from the trout tests, whereas the EC20 for copper,
      lead, or zinc for the sturgeon were lower than those EC20s for the trout. When
      the EC20s from the present study were included in compiled toxicity databases for
      all freshwater species, species mean chronic value for white sturgeon was in a
      relatively low percentile of the species sensitivity distribution for copper (9th
      percentile) and in the middle percentile for cadmium (55th percentile), zinc
      (40th percentile), or lead (50th percentile). However, the species mean chronic
      value for rainbow trout was in a high percentile for copper, lead, and zinc
      (~68th-82nd percentile), but in a low percentile for cadmium (23rd percentile).
      The trout EC20s for each of the 4 metals and the sturgeon EC20s for cadmium or
      lead were above US Environmental Protection Agency chronic ambient water quality
      criteria (AWQC) or Washington State chronic water quality standards (WQS),
      whereas the sturgeon EC20s for copper or zinc were approximately equal to or
      below the chronic AWQC and WQS. In addition, acute 50% effect concentrations
      (EC50s) for copper obtained in the first 4 d of the chronic sturgeon test were
      below the final acute value used to derive acute AWQC and below acute WQS for
      copper.

PMID- 24862827
TI  - Biochemical and physiological characterization of a new Na(+)-channel specific
      peptide from the venom of the Argentinean scorpion Tityus trivittatus.
AB  - A new peptide with 61 amino acids cross-linked by 4 disulfide bridges, with
      molecular weight of 6938.12Da, and an amidated C-terminal amino acid residue was
      purified and characterized. The primary structure was obtained by direct Edman
      degradation and sequencing its gene. The peptide is lethal to mammals and was
      shown to be similar (95% identity) to toxin Ts1 (gamma toxin) from the Brazilian
      scorpion Tityus serrulatus; it was named Tt1g (from T. trivittatus toxin 1 gamma
      like). Tt1g was assayed on several sub-types of Na(+)-channels showing
      displacement of the currents to more negative voltages, being the hNav1.3 the
      most affected channel. This toxin displays characteristics typical to the beta
      type sodium scorpion toxins. Lethality tests and physiological assays indicate
      that this peptide is probably the most important toxic component of this species
      of scorpion, known for causing human fatalities in the South American continent. 

PMID- 24862828
TI  - Selection of reference genes for expression analysis in Diuraphis noxia
      (Hemiptera: Aphididae) fed on resistant and susceptible wheat plants.
AB  - The Russian wheat aphid (RWA), Diuraphis noxia Kurdjumov, is a major global pest
      of wheat and barley production that causes enormous economic damage. Few studies
      have been conducted to explore and decipher the molecular basis of RWA strategies
      to evade plant defense mechanisms. Gene expression studies of RWA in response to
      wheat genotypes carrying different RWA resistance genes have been initiated in
      our group; however, a secure and accurate understanding of RWA gene expression is
      dependent on identification of suitable reference genes. This study analyzed
      expression profiles of five potential reference genes selected and sequenced
      during RNA sequencing experiments. The expression of genes coding for actin and
      ribosomal protein L27 was comparatively less variable in RWA fed on different
      wheat hosts. Results of geNorm, NormFinder, and BestKeeper expression analyses
      support the use of actin and ribosomal protein L27 in RT-qPCR studies of RWA gene
      expression in studies involving RWA-wheat interactions. 

PMID- 24862829
TI  - Effects of thyme as a feed additive in broiler chickens on thymol in gut
      contents, blood plasma, liver and muscle.
AB  - BACKGROUND: Aromatic herbs as feed additives in animal production are
      encountering growing interest, but data on the fate of the aromatic compounds
      from the plant in the animal body are very scarce. In the present study, thyme
      (Thymus vulgaris) herb consisting of leaves and flowers without stems was used as
      an ingredient in the diet for broilers. The herb was fed for 35 days to five
      groups of broilers (0, 0.1, 0.2, 0.3, and 1% w/w in the diet). Animal performance
      and the concentrations of the main essential oil component from thyme, thymol,
      were measured in gut contents, plasma and liver and muscle tissues using solid
      phase microextraction and gas chromatography/mass spectrometry. RESULTS: There
      were no differences between the groups in feed intake, daily weight gain, feed
      conversion and slaughter weight. Thymol was detected in gut contents, plasma and
      liver and muscle tissues. Increased intestinal thymol concentrations were found
      in the group with 1% thyme compared with the other groups (P < 0.05). In liver
      and muscle tissues the thymol levels were close to the limit of quantification.
      CONCLUSION: The data do not indicate a positive effect of thyme on animal
      performance. With high dietary levels of thyme herb, thymol concentrations
      increased in gut contents and plasma but were very low in edible tissues such as
      liver and flesh. (c) 2014 Society of Chemical Industry.

PMID- 24862830
TI  - Is it time to test biguanide metformin in the treatment of melanoma?
AB  - Metformin is the most widely used antidiabetic drug that belongs to the biguanide
      class. It is very well tolerated and has the major clinical advantage of not
      inducing hypoglycemia. Metformin decreases hepatic glucose production via a
      mechanism requiring liver kinase B1, which controls the metabolic checkpoint, AMP
      activated protein kinase-mammalian target of rapamycin and neoglucogenic genes.
      The effects of metformin on this pathway results in reduced protein synthesis and
      cell proliferation. These observations have given the impetus for many
      investigations on the role of metformin in the regulation of tumor cell
      proliferation, cell-cycle regulation, apoptosis, and autophagy. Encouraging
      results from these studies have shown that metformin could potentially be used as
      an efficient anticancer drug in various neoplasms such as prostate, breast, lung,
      pancreas cancers, and melanoma. These findings are strengthened by retrospective
      epidemiological studies that have found a decrease in cancer risk in diabetic
      patients treated with metformin. In this review, we have focused our discussion
      on recent molecular mechanisms of metformin that have been described in various
      solid tumors in general and in melanoma in particular. 

PMID- 24862832
TI  - Facial onset sensory and motor neuronopathy (FOSMN) of childhood onset.

PMID- 24862831
TI  - Greenness and allergies: evidence of differential associations in two areas in
      Germany.
AB  - BACKGROUND: Positive greenness effects on health are increasingly reported,
      although studies on allergic outcomes remain limited and conflicting. We examined
      whether residential greenness is associated with childhood doctor diagnosed
      allergic rhinitis, eyes and nose symptoms and aeroallergen sensitisation using
      two combined birth cohorts (GINIplus and LISAplus) followed from birth to 10
      years in northern and southern Germany (Ntotal=5803). METHODS: Mean residential
      greenness in a 500 m buffer around the 10-year home addresses was defined using
      the Normalized Difference Vegetation Index, a green biomass density indicator.
      Longitudinal associations were assessed per study area (GINI/LISA South and
      GINI/LISA North) using generalised estimation equations adjusted for host and
      environmental covariates. RESULTS: Despite identical study designs and
      statistical modelling, greenness effects differed across the two study areas.
      Associations were elevated for allergic rhinitis and eyes and nose symptoms in
      the urban GINI/LISA South area. In contrast, risk estimates were significantly
      below one for these outcomes and aeroallergen sensitisation in rural GINI/LISA
      North. Area-specific associations were similar across buffer sizes and addresses
      (birth and 6 years) and remained heterogeneous after air pollution and population
      density stratification. CONCLUSIONS: Existing and future single-area studies on
      greenness and green spaces should be interpreted with caution.

PMID- 24862834
TI  - Direct in situ nitridation of nanostructured metal oxide deposited semiconductor
      interfaces: tuning the response of reversibly interacting sensor sites.
AB  - Metal-oxide nanostructure-decorated extrinsic semiconductor interfaces modified
      through in situ nitridation greatly expand the range of sensor interface
      response. Select metal-oxide sites, deposited to an n-type nanopore-coated
      microporous interface, direct a dominant electron-transduction process for
      reversible chemical sensing, which minimizes chemical-bond formation. The oxides
      are modified to decrease their Lewis acidity through a weak interaction to form
      metal oxynitride sites. Conductometric and X-ray photoelectron spectroscopy
      measurements demonstrate that in situ treatment changes the reversible
      interaction with the analytes NH3 and NO. The sensor range is extended, which
      creates a distinct new family of responses determined by the Lewis
      acidity/basicity of a given analyte relative to that of the nanostructures chosen
      to decorate the interface. The analyte response, broadened in a substantial and
      predictable way by nitridation, is explained by the recently developing inverse
      hard/soft acid/base model (IHSAB) of reversible electron transduction. 

PMID- 24862833
TI  - Immune dysfunction in bipolar disorder and suicide risk: is there an association
      between peripheral corticotropin-releasing hormone and interleukin-1beta?
AB  - OBJECTIVE: The aim of the present study was to investigate the relationship
      between peripheral levels of corticotropin-releasing hormone (CRH) and
      interleukin-1beta (IL-1beta) in individuals with bipolar disorder (BD) with and
      without suicide risk (SR), and controls. METHODS: A total of 120 young adults (40
      controls, 40 subjects with BD without SR, and 40 subjects with BD with SR) were
      enrolled from a population-based study carried out in the city of Pelotas,
      Brazil. BD and SR were assessed through the Mini International Neuropsychiatric
      Interview (MINI 5.0), and peripheral markers were evaluated by enzyme-linked
      immunosorbent assay (ELISA). RESULTS: Levels of CRH were significantly lower both
      in subjects with BD without SR (p = 0.04) and subjects with BD with SR (p = 0.02)
      when compared to controls. However, levels of IL-1beta were increased in subjects
      with BD with SR (p = 0.05) when compared to controls. Sociodemographic and
      clinical variables, current mood episode, and use of psychiatric medications were
      not associated with changes in these markers. No correlation was found between
      peripheral levels of CRH and IL-1beta (p = 0.60) in the population or in the BD
      with SR group (p = 0.88). CONCLUSIONS: These results suggest that peripheral
      mechanisms linking stress hormones and the immune system might be critical
      patterns involved in suicidal behavior associated with BD.

PMID- 24862835
TI  - Multiple sclerosis in gulf war era veterans. 2. Military deployment and risk of
      multiple sclerosis in the first gulf war.
AB  - BACKGROUND: Concern has been raised that US veterans of the 1990-1991 Gulf War
      (GW1) may be at increased risk to develop neurologic disease. METHODS: An
      incident cohort of multiple sclerosis (MS) and other demyelinating disease (ODD)
      was assembled from the US military comprising the Gulf War era (1990-2007). Cases
      of MS and ODD meeting standard diagnostic criteria were matched to a database of
      all active duty personnel from the Department of Defense. Relative risk (RR)
      estimates for MS and all demyelinating disease based on onset, deployment status,
      and exposures were calculated. RESULTS: For GW1, a total of 1,841 incident cases
      of definite MS and ODD were identified, with 387 among 696,118 deployed and 1,454
      among 1,786,215 nondeployed personnel. The RR for MS alone among those deployed
      compared to those nondeployed was 0.69 (confidence interval, CI: 0.61-0.78), with
      0.72 (CI: 0.62-0.83) in men and 0.96 (CI: 0.75-1.22) in women. Deployment was
      also nonsignificant or protective as an MS risk factor across racial groups, all
      age groups, and each military service. RRs for MS by service were: Air Force 0.71
      (CI: 0.53-0.96), Army 0.80 (CI: 0.67-0.96), Marines 0.96 (CI: 0.63-1.47), and
      Navy 0.56 (CI: 0.43-0.74). CONCLUSION: Military deployment to GW1 was not a risk
      factor for developing MS.

PMID- 24862836
TI  - A flexible format interdisciplinary treatment and rehabilitation program for
      chronic daily headache: patient clinical features, resource utilization and
      outcomes.
AB  - OBJECTIVE: To describe the demographics, diagnoses, program duration, human
      resource utilization and outcomes of patients with chronic daily headache treated
      in an ambulatory, interdisciplinary, flexible format, treatment and
      rehabilitation program. BACKGROUND: Research indicates that multidisciplinary
      care is an effective approach to manage chronic daily headache, but little is
      known about the resources needed for effective care. METHODS: The study was a
      secondary data analysis within a cohort design of previously collected data.
      Patients completed questionnaires and outcome measures on admission and
      discharge. Diagnoses were extracted from patient charts by professional health
      records personnel. A central scheduling database provided patient-specific
      clinician care hours by discipline and type (direct, indirect, group) as well as
      overall program duration. RESULTS: One hundred and eighteen patients were studied
      (mean age 41.1 +/- 10.4   [x +/- SD], 80% female). Sixty-two patients (52.5%)
      completed the program ("completers"). Migraine was the most common diagnosis.
      Thirty-six percent of patients had medication overuse. Average pain, mood,
      disability, and quality of life were significantly improved in completers (P <
      .001). They utilized 76 +/- 45.1   (x +/- SD ) total hours of care delivered over
      a mean of 129.7 +/- 66.1 weeks. CONCLUSION: Our study provides evidence that
      ambulatory, interdisciplinary, flexible format, treatment and rehabilitation
      programs are effective in the treatment of chronic daily headache, and we provide
      data on the resources used by our program in the treatment and rehabilitation of
      these patients.

PMID- 24862837
TI  - Hyperpolarized choline as an MR imaging molecular probe: feasibility of in vivo
      imaging in a rat model.
AB  - PURPOSE: To assess the feasibility of choline MRI using a new choline molecular
      probe for dynamic nuclear polarization (DNP) hyperpolarized MRI. MATERIALS AND
      METHODS: Male Sprague-Dawley rats with an average weight of 400 +/- 20 g (n = 5),
      were anesthetized and injection tubing was placed in the tail vein. [1,1,2,2-D4 ,
      1-(13) C]choline chloride (CMP1) was hyperpolarized by DNP and injected into rats
      at doses ranging from 12.6 to 50.0 mg/kg. Coronal projection (13) C imaging was
      performed on a 3 Tesla clinical MRI scanner (bore size 60 cm) using a variable
      flip angle gradient echo sequence. Images were acquired 15 to 45 s after the
      start of bolus injection. Signal intensities in regions of interest were
      determined at each time point and compared. RESULTS: (13) C MRI images of
      hyperpolarized CMP1 at a 50 mg/kg dose showed time-dependent organ distribution
      patterns. At 15 s, high intensities were observed in the inferior vena cava,
      heart, aorta, and kidneys. At 30 s, most of the signal intensity was localized to
      the kidneys. These distribution patterns were reproduced using 12.6 and 25 mg/kg
      doses. At 45 s, only signal in the kidneys was detected. CONCLUSION:
      Hyperpolarized choline imaging with MRI is feasible using a stable-isotope
      labeled choline analog (CMP1). Nonradioactive imaging of choline accumulation may
      provide a new investigatory dimension for kidney physiology. J. Magn. Reson.
      Imaging 2015;41:917-923. (c) 2014 Wiley Periodicals, Inc.

PMID- 24862838
TI  - Water temperature and fish growth: otoliths predict growth patterns of a marine
      fish in a changing climate.
AB  - Ecological modeling shows that even small, gradual changes in body size in a fish
      population can have large effects on natural mortality, biomass, and catch.
      However, efforts to model the impact of climate change on fish growth have been
      hampered by a lack of long-term (multidecadal) data needed to understand the
      effects of temperature on growth rates in natural environments. We used a
      combination of dendrochronology techniques and additive mixed-effects modeling to
      examine the sensitivity of growth in a long-lived (up to 70 years), endemic
      marine fish, the western blue groper (Achoerodus gouldii), to changes in water
      temperature. A multi-decadal biochronology (1952-2003) of growth was constructed
      from the otoliths of 56 fish collected off the southwestern coast of Western
      Australia, and we tested for correlations between the mean index chronology and a
      range of potential environmental drivers. The chronology was significantly
      correlated with sea surface temperature in the region, but common variance among
      individuals was low. This suggests that this species has been relatively
      insensitive to past variations in climate. Growth increment and age data were
      also used in an additive mixed model to predict otolith growth and body size
      later this century. Although growth was relatively insensitive to changes in
      temperature, the model results suggested that a fish aged 20 in 2099 would have
      an otolith about 10% larger and a body size about 5% larger than a fish aged 20
      in 1977. Our study shows that species or populations regarded as relatively
      insensitive to climate change could still undergo significant changes in growth
      rate and body size that are likely to have important effects on the productivity
      and yield of fisheries.

PMID- 24862839
TI  - Identification of the putative ancestral allele of bovine single-nucleotide
      polymorphisms.
AB  - Identifying the action of natural selection from patterns of standing genetic
      variation has long been of interest to the population genetic community. Thanks
      to the availability of large single-nucleotide polymorphism (SNP) data sets for
      many species and of high-throughput SNP genotyping methods, whole-genomic surveys
      to detect selective sweeps are now possible. Knowing the ancestral allele
      increases the power to detect selection. We present here a comparative genomic
      approach to determine the putative ancestral allele of bovine SNPs deposited in
      public databases. We analysed 19,551,488 SNPs and identified the putative
      ancestral allele for 14,339,107 SNPs. Our predicted ancestral alleles were in
      agreement with ancestral alleles detected by genotyping outgroup species for 97%
      SNPs from the BovineSNP50 BeadChip. This comparison indicates that our
      comparative genomic-based approach to identify putative ancestral alleles is
      reliable.

PMID- 24862840
TI  - Transitional care interventions to prevent readmissions for persons with heart
      failure: a systematic review and meta-analysis.
AB  - BACKGROUND: Nearly 25% of patients hospitalized with heart failure (HF) are
      readmitted within 30 days. PURPOSE: To assess the efficacy, comparative
      effectiveness, and harms of transitional care interventions to reduce readmission
      and mortality rates for adults hospitalized with HF. DATA SOURCES: MEDLINE,
      Cochrane Library, CINAHL, ClinicalTrials.gov, and World Health Organization
      International Clinical Trials Registry Platform (1 January 1990 to late October
      2013). STUDY SELECTION: Two reviewers independently selected randomized,
      controlled trials published in English reporting a readmission or mortality rate
      within 6 months of an index hospitalization. DATA EXTRACTION: One reviewer
      extracted data, and another checked accuracy. Two reviewers assessed risk of bias
      and graded strength of evidence (SOE). DATA SYNTHESIS: Forty-seven trials were
      included. Most enrolled adults with moderate to severe HF and a mean age of 70
      years. Few trials reported 30-day readmission rates. At 30 days, a high-intensity
      home-visiting program reduced all-cause readmission and the composite end point
      (all-cause readmission or death; low SOE). Over 3 to 6 months, home-visiting
      programs and multidisciplinary heart failure (MDS-HF) clinic interventions
      reduced all-cause readmission (high SOE). Home-visiting programs reduced HF
      specific readmission and the composite end point (moderate SOE). Structured
      telephone support (STS) interventions reduced HF-specific readmission (high SOE)
      but not all-cause readmissions (moderate SOE). Home-visiting programs, MDS-HF
      clinics, and STS interventions produced a mortality benefit. Neither
      telemonitoring nor primarily educational interventions reduced readmission or
      mortality rates. LIMITATIONS: Few trials reported 30-day readmission rates. Usual
      care was heterogeneous and sometimes not adequately described. CONCLUSION: Home
      visiting programs and MDS-HF clinics reduced all-cause readmission and mortality;
      STS reduced HF-specific readmission and mortality. These interventions should
      receive the greatest consideration by systems or providers seeking to implement
      transitional care interventions for persons with HF. PRIMARY FUNDING SOURCE:
      Agency for Healthcare Research and Quality.

PMID- 24862843
TI  - High resolution trapped ion mobility spectrometery of peptides.
AB  - In the present work, we employ trapped ion mobility spectrometry (TIMS) for
      conformational analysis of several model peptides. The TIMS distributions are
      extensively compared to recent ion mobility spectrometry (IMS) studies reported
      in the literature. At a resolving power (R) exceeding 250, many new features,
      otherwise hidden by lower resolution IMS analyzers, are revealed. Though still
      principally limited by the plurality of conformational states, at present, TIMS
      offers R up to ~3 to 8 times greater than modern drift tube or traveling wave IMS
      techniques, respectively. Unlike differential IMS, TIMS not only is able to
      resolve congested conformational features but also can be used to determine
      information about their relative size, via the ion-neutral collision cross
      section, offering a powerful new platform to probe the structure and dynamics of
      biochemical systems in the gas phase. 

PMID- 24862841
TI  - Binding site multiplicity with fatty acid ligands: implications for the
      regulation of PKR kinase autophosphorylation with palmitate.
AB  - Saturated long chain-free fatty acids (FFAs), especially palmitate, have been
      implicated in apoptosis by inhibiting the activity of PKR (double-stranded RNA
      dependent protein kinase). We recently found evidence that palmitate interacts
      directly with the kinase domain of PKR, subsequently inhibiting the
      autophosphorylation of PKR. To investigate the interactions of palmitate with PKR
      and its effects on PKR autophosphorylation, we performed extensive unbiased MD
      simulations combined with biochemical and biophysical experiments. The
      simulations predict multiple putative binding sites of palmitate on both the
      phosphorylated and unphosphorylated PKR with similar binding affinities. Ligand
      protein interactions involving a large variety of different binding modes
      challenge the conventional view of highly specific, single binding sites. Key
      interactions of palmitate involve the alphaC-helix of PKR, especially near
      residue R307. Experimental mutation of R307 was found to affect palmitate binding
      and reduce its inhibitory effect. Based on this study a new allosteric mechanism
      is proposed where palmitate binding to the alphaC-helix prevents the inactive-to
      active transition of PKR and subsequently reduces its ability to
      autophosphorylate.

PMID- 24862842
TI  - Food intake and overweight in school-aged children in Germany: Results of the
      GINIplus and LISAplus studies.
AB  - OBJECTIVE: To investigate the cross-sectional association between food intake and
      overweight in children. METHODS: Height and weight were measured in 2,565 school
      aged children. Intakes of 11 food groups were categorized (low, medium and high)
      using specific tertile cutoffs. Multivariate energy partition models were
      applied. Adjustment included energy intake from other food groups, city, family
      income, parental education and 'screen' time. Possible underreporters were
      identified and used in sensitivity analyses. RESULTS: Compared to low intake,
      high intakes of meat, fish, beverages and bakery products were associated with
      greater BMI z-scores [beta (95% CI) = 0.32 (0.21, 0.42), 0.13 (0.03, 0.24), 0.23
      (0.11, 0.35) and 0.10 (-0.01, 0.20)] and increased risk of being overweight [odds
      ratio (OR) (95% CI) = 2.08 (1.58, 2.73), 1.39 (1.08, 1.80), 1.36 (1.01, 1.84) and
      1.62 (1.24, 2.11)]. Conversely, medium and high intakes of confectionery were
      associated with smaller BMI z-scores [beta = -0.18 (-0.28, -0.07) and -0.22 (
      0.33, -0.12)] and decreased risk of being overweight [OR = 0.64 (0.50, 0.83) and
      0.53 (0.40, 0.68)]. These associations were robust to sensitivity analyses.
      CONCLUSIONS: Intakes of meat, fish, beverages and bakery products correlate with
      body weight status.

PMID- 24862845
TI  - Editorial comment on Zhang et al.: Impact of metabolic syndrome on benign
      prostatic hyperplasia in elderly Chinese men.

PMID- 24862844
TI  - The origins of ability and automaticity in tactile spatial perception.

PMID- 24862846
TI  - miR-330-5p targets tyrosinase and induces depigmentation.

PMID- 24862848
TI  - Observed, Executed, and Imagined Action Representations can be Decoded From
      Ventral and Dorsal Areas.
AB  - Previous functional magnetic resonance imaging (fMRI) research on action
      observation has emphasized the role of putative mirror neuron areas such as
      Broca's area, ventral premotor cortex, and the inferior parietal lobule. However,
      recent evidence suggests action observation involves many distributed cortical
      regions, including dorsal premotor and superior parietal cortex. How these
      different regions relate to traditional mirror neuron areas, and whether
      traditional mirror neuron areas play a special role in action representation, is
      unclear. Here we use multi-voxel pattern analysis (MVPA) to show that action
      representations, including observation, imagery, and execution of reaching
      movements: (1) are distributed across both dorsal (superior) and ventral
      (inferior) premotor and parietal areas; (2) can be decoded from areas that are
      jointly activated by observation, execution, and imagery of reaching movements,
      even in cases of equal-amplitude blood oxygen level-dependent (BOLD) responses;
      and (3) can be equally accurately classified from either posterior parietal or
      frontal (premotor and inferior frontal) regions. These results challenge the
      presumed dominance of traditional mirror neuron areas such as Broca's area in
      action observation and action representation more generally. Unlike traditional
      univariate fMRI analyses, MVPA was able to discriminate between imagined and
      observed movements from previously indistinguishable BOLD activations in commonly
      activated regions, suggesting finer-grained distributed patterns of activation. 

PMID- 24862849
TI  - Light propagation along the pericardium meridian at human wrist as evidenced by
      the optical experiment and Monte Carlo method.
AB  - OBJECTIVE: To explore the characteristics of light propagation along the
      Pericardium Meridian and its surrounding areas at human wrist by using optical
      experiment and Monte Carlo method. METHODS: An experiment was carried out to
      obtain the distribution of diffuse light on Pericardium Meridian line and its
      surrounding areas at the wrist, and then a simplified model based on the
      anatomical structure was proposed to simulate the light transportation within the
      same area by using Monte Carlo method. RESULTS: The experimental results showed
      strong accordance with the Monte Carlo simulation that the light propagation
      along the Pericardium Meridian had an advantage over its surrounding areas at the
      wrist. CONCLUSION: The advantage of light transport along Pericardium Merdian
      line was related to components and structure of tissue, also the anatomical
      structure of the area that the Pericardium Meridian line runs.

PMID- 24862850
TI  - Effect of Ren meridian acupoints moxibustion on light propagation along the
      pericardium meridian at human wrist.
AB  - OBJECTIVE: To explore the relationship between acupoints and meridians. METHODS:
      Researches were performed on 45 healthy people under the same conditions. The
      diffuse light intensity of the Pericardium meridian and its surrounding areas
      were measured before and after warming moxibustion on three acupoints [Shimen
      (RN5), Qihai (RN6), and Yinjiao (RN7)] of Ren meridian below umbilicus in the
      same way. Then two sets of data of each sample were used for statistics and
      analysis, as well as the three-dimensional distribution figures. Statistical
      definition of probability value was used to evaluate the effect made by
      moxibustion. RESULTS: After moxibustion, the diffuse light intensity presented
      significant changes in 25 samples (P<0.05), enhanced in 15 people (P<0.05) and
      decreased in 10 (P<0.05). It was consistent with the classification by
      questionnaire interviews of somatotypes. In addition, diffuse light changed more
      obviously on Pericardium than non-meridian areas. It was distinct in the three
      dimensional distribution figures. CONCLUSIONS: Diffuse light changes happened in
      entire measure sites demonstrated that acupoints of Ren meridian moxibustion
      could affect the light propagation of wrist, especially on the Pericardium
      meridian. It gave an expression to meridians interconnection as said in the
      Chinese medicine theory. The two classifications made by light propagation
      changes were experimental corroboration of that personal physical differences
      affected the manipulation of Chinese acupuncture and moxibustion treatment. These
      above provided some implications or new directions to future meridian researches.

PMID- 24862851
TI  - Prenatal caffeine intake differently affects synaptic proteins during fetal brain
      development.
AB  - Caffeine is the psychostimulant most consumed worldwide. However, little is known
      about its effects during fetal brain development. In this study, adult female
      Wistar rats received caffeine in drinking water (0.1, 0.3 and 1.0 g/L) during the
      active cycle in weekdays, two weeks before mating and throughout pregnancy.
      Cerebral cortex and hippocampus from embryonic stages 18 or 20 (E18 or E20,
      respectively) were collected for immunodetection of the following synaptic
      proteins: brain-derived neurotrophic factor (BDNF), TrkB receptor, Sonic Hedgehog
      (Shh), Growth Associated Protein 43 (GAP-43) and Synaptosomal-associated Protein
      25 (SNAP-25). Besides, the estimation of NeuN-stained nuclei (mature neurons) and
      non-neuronal nuclei was verified in both brain regions and embryonic periods.
      Caffeine (1.0 g/L) decreased the body weight of embryos at E20. Cortical BDNF at
      E18 was decreased by caffeine (1.0 g/L), while it increased at E20, with no major
      effects on TrkB receptors. In the hippocampus, caffeine decreased TrkB receptor
      only at E18, with no effects on BDNF. Moderate and high doses of caffeine
      promoted an increase in Shh in both brain regions at E18, and in the hippocampus
      at E20. Caffeine (0.3g/L) decreased GAP-43 only in the hippocampus at E18. The
      NeuN-stained nuclei increased in the cortex at E20 by lower dose and in the
      hippocampus at E18 by moderate dose. Our data revealed that caffeine transitorily
      affect synaptic proteins during fetal brain development. The increased number of
      NeuN-stained nuclei by prenatal caffeine suggests a possible acceleration of the
      telencephalon maturation. Although some modifications in the synaptic proteins
      were transient, our data suggest that caffeine even in lower doses may alter the
      fetal brain development.

PMID- 24862852
TI  - Arsenic exposure increases maternal but not cord serum IgG in Bangladesh.
AB  - BACKGROUND: Thousands of pregnant women are exposed to arsenic (As), which has
      been shown to lead to a higher risk of maternal and infant morbidity. We
      hypothesized that As-induced modifications to the humoral immune system may be
      partly responsible, and examined the relationship between As and immunoglobulin G
      (IgG). METHODS: Pregnant women were recruited in As-contaminated rural areas in
      Bangladesh. Blood and urine samples, and questionnaire data were collected. We
      analyzed data from 202 pregnant women and a subset of 121 mother-infant pairs.
      Urinary As was measured on inductively coupled plasma-mass spectrometry and
      adjusted with specific gravity (U-AsSG ). Maternal (IgGmat ) and cord (IgGcord )
      serum total IgG were measured using immunoturbidity assay. RESULTS: The geometric
      mean U-AsSG (n = 202) was 69 MUg/L (range, 3.1-1356 MUg/L). Urinary-AsSG was
      significantly associated with IgGmat (n = 202; (r = 0.24; 95% confidence interval
      [CI]: 0.10-0.36; P < 0.001) and remained so after the inclusion of maternal
      associated variables in a multiple-regression model (beta = 1.26; 95%CI: 0.47
      2.05; P < 0.01). U-AsSG , however, was not significantly associated with IgGcord
      (n = 121), while IgGmat and IgGcord were also not associated with each other.
      CONCLUSIONS: Maternal As exposure was positively associated with IgGmat but not
      IgGcord . Elevated IgGmat may have implications as regards maternal morbidity and
      the placental transfer of specific IgGs. Further studies are required to better
      understand how As may affect maternal and child health by modifying the humoral
      immune system.

PMID- 24862853
TI  - MiR-15a/b promote adipogenesis in porcine pre-adipocyte via repressing FoxO1.
AB  - Diabetes and many other metabolism syndromes are closely related to obesity. To
      reveal the underlying mechanism of fat deposition, an increasing number of
      studies are focusing on the functions of miRNAs during adipocytes development.
      Previous studies have proved that miR-15a/b play important roles in multiple
      physiological processes; however, their functions during adipogenesis remain
      unclear. To reveal this, we detected the expression profiles of miR-15a/b during
      adipogenesis in porcine pre-adipocyte, and found that their expression levels
      increased in the early stage of adipocyte differentiation and dropped after day
      4. Moreover, over-expression of miR-15a/b in porcine pre-adipocytes promoted
      adipocyte differentiation and lipid accumulation. Target genes of miR-15a/b were
      predicted and examined, which revealed that Forkhead box protein O1 (FoxO1) is
      the target gene of miR-15a/b. The inhibition of FoxO1 expression level caused by
      miR-15a/b over-expression had a positive effect on adipogenesis. Thus, we
      conclude that miR-15a/b promote adipogenesis in porcine pre-adipocyte via
      repressing FoxO1. 

PMID- 24862855
TI  - Sonic hedgehog signaling in the postnatal brain.
AB  - Sonic hedgehog (Shh) is a pleiotropic factor in the developing central nervous
      system (CNS), driving proliferation, specification, and axonal targeting in
      multiple sites within the forebrain, hindbrain, and spinal cord. Studies in
      embryonic CNS have shown how gradients of this morphogen are translated by
      neuroepithelial precursors to determine the types of neurons and glial cells they
      produce [1,2]. Shh also has a well-characterized role as a mitogen for specific
      progenitor cell types in neural development [3,4]. As we begin to appreciate that
      Shh continues to act in the adult brain, a central question is what functional
      role this ligand plays when major morphogenetic and proliferative processes are
      no longer in operation. A second fundamental question is whether similar
      signaling mechanisms operate in embryonic and adult CNS. In the two major
      germinal zones of the adult brain, Shh signaling modulates the self-renewal and
      specification of astrocyte-like primary progenitors, frequently referred to as
      neural stem cells (NSCs). It also may regulate the response of the mature brain
      to injury, as Shh signaling has been variously proposed to enhance or inhibit the
      development of a reactive astrocyte phenotype. The identity of cells producing
      the Shh ligand, and the conditions that trigger its release, are also areas of
      growing interest; both germinal zones in the adult brain contain Shh-responsive
      cells but do not autonomously produce this ligand. Here, we review recent
      findings revealing the function of this fascinating pathway in the postnatal and
      adult brain, and highlight ongoing areas of investigation into its actions long
      past the time when it shapes the developing brain. 

PMID- 24862858
TI  - Nematode Tango Milonguero - the C. elegans male's search for the hermaphrodite
      vulva.
AB  - The vulva search corresponds to the first step of mating in Caenorhabditis
      elegans wherein the male recognizes a potential mate through contact and
      commences a systematic, contact-based search of her surface for the vulva. During
      this 'dance' the male presses his tail genitalia firmly against the hermaphrodite
      surface and moves backward, modulating tail posture to effect changes in search
      trajectory. Upon sensing the vulva, the male pauses and the insemination phase of
      mating begins. External tail sensilla, the rays, induce and guide the male's
      search by registering hermaphrodite surface cues. C. elegans male mating
      behavior, like many other animate interactions (such as predator-prey
      interactions or intrasexual aggression), is performed at close quarters and
      requires that participants constantly adjust their movement with respect to one
      another on a moment-by-moment basis. The design features of the supporting
      circuitry explain simultaneously the robustness, speed and acuity of the male's
      behavior and its male-specific nature. Processing at all levels of the circuitry
      appears to be distributed. Cellular components exhibit both partial redundancy
      (thus conferring robustness in output) and subtle functional differences
      (predicted to confer acuity). Surprisingly, gender-shared cell types feature
      prominently in the circuitry. Male-specific components form sensory pathways that
      render downstream gender-shared circuits responsive to mate cues, while other
      male cells act to augment gender-shared cell activity. Overall, the attributes of
      the vulva search circuitry provide insight into principles guiding the design and
      operation of circuits supporting dynamic social behaviors expressed by more
      complex and less tractable animal species. 

PMID- 24862856
TI  - Transcriptional regulation of graded Hedgehog signaling.
AB  - The Hedgehog (Hh) pathway plays conserved roles in regulating a diverse spectrum
      of developmental processes. In some developmental contexts, a gradient of Hh
      protein specifies multiple cell types in a dose-dependent fashion, thereby acting
      as a morphogen. Hh signaling ultimately acts on the transcriptional level through
      GLI proteins. In the presence of Hh signaling full length GLI proteins act as
      transcriptional activators of target genes. Conversely, in the absence of Hh, GLI
      proteins act as transcriptional repressors. This review will highlight mechanisms
      contributing to how graded Hh signaling might translate to differential GLI
      activity and be interpreted into distinct transcriptional responses. 

PMID- 24862854
TI  - Canonical and non-canonical Hedgehog signalling and the control of metabolism.
AB  - Obesity and diabetes represent key healthcare challenges of our day, affecting
      upwards of one billion people worldwide. These individuals are at higher risk for
      cancer, stroke, blindness, heart and cardiovascular disease, and to date, have no
      effective long-term treatment options available. Recent and accumulating evidence
      has implicated the developmental morphogen Hedgehog and its downstream signalling
      in metabolic control. Generally thought to be quiescent in adults, Hedgehog is
      associated with several human cancers, and as such, has already emerged as a
      therapeutic target in oncology. Here, we attempt to give a comprehensive overview
      of the key signalling events associated with both canonical and non-canonical
      Hedgehog signalling, and highlight the increasingly complex regulatory modalities
      that appear to link Hedgehog and control metabolism. We highlight these key
      findings and discuss their impact for therapeutic development, cancer and
      metabolic disease. 

PMID- 24862859
TI  - Supervised learning with decision margins in pools of spiking neurons.
AB  - Learning to categorise sensory inputs by generalising from a few examples whose
      category is precisely known is a crucial step for the brain to produce
      appropriate behavioural responses. At the neuronal level, this may be performed
      by adaptation of synaptic weights under the influence of a training signal, in
      order to group spiking patterns impinging on the neuron. Here we describe a
      framework that allows spiking neurons to perform such "supervised learning",
      using principles similar to the Support Vector Machine, a well-established and
      robust classifier. Using a hinge-loss error function, we show that requesting a
      margin similar to that of the SVM improves performance on linearly non-separable
      problems. Moreover, we show that using pools of neurons to discriminate
      categories can also increase the performance by sharing the load among neurons. 

PMID- 24862860
TI  - Protection of skin with subcutaneous administration of 5% dextrose in water
      during superficial radiofrequency ablation in a rabbit model.
AB  - PURPOSE: This study was to evaluate the efficacy of subcutaneous administration
      of 5% dextrose in water (D5W), to prevent skin injury during radiofrequency (RF)
      ablation. MATERIALS AND METHODS: Twenty-four rabbits were divided into three
      groups: a pre-injection group, a perfusion group, and a control group. Ablative
      zones were created in the superficial part of the thigh muscle for 6 min. A
      needle was placed subcutaneously for injection of D5W, and a thermal sensor was
      positioned nearby for real-time temperature monitoring. The sizes of the ablative
      zones were measured by contrast-enhanced ultrasonography, and severity of the
      observed skin injury were scored semi-quantitatively and compared. RESULTS: The
      highest temperature, the duration of the temperature above 50  degrees C, and the
      rise time of the post-procedure temperature were all highest in the control group
      (p < 0.001), while these values were lower in the perfusion group than those in
      the pre-injection group (p < 0.001). Post-procedure skin injury was most severe
      in the control group (p < 0.001). On post-procedure day 1, no significant
      difference was found between the skin injury of the pre-injection group and the
      perfusion group (p = 0.091), while the skin injury of the perfusion group was
      less severe than that of the pre-injection group on post-procedure day 14 (p =
      0.004). No significant difference was found in the sizes of the ablative zones
      among the groups (p = 0.720). CONCLUSION: Subcutaneous perfusion with D5W is
      effective in protecting the skin against burns during RF ablation without
      compromising the effect of ablation.

PMID- 24862857
TI  - Cadence of procreation: orchestrating embryo-uterine interactions.
AB  - Embryo implantation in eutherian mammals is a highly complex process and requires
      reciprocal communication between different cell types of the embryo at the
      blastocyst stage and receptive uterus. The events of implantation are dynamic and
      highly orchestrated over a species-specific period of time with distinctive and
      overlapping expression of many genes. Delayed implantation in different species
      has helped elucidate some of the intricacies of implantation timing and different
      modes of the implantation process. How these events are coordinated in time and
      space are not clearly understood. We discuss potential regulators of the precise
      timing of these events with respect to central and local clock mechanisms. This
      review focuses on the timing and synchronization of early pregnancy events in
      mouse and consequences of their aberrations at later stages of pregnancy. 

PMID- 24862861
TI  - Two- and three-dimensional transvaginal ultrasound with power Doppler angiography
      and gel infusion sonography for diagnosis of endometrial malignancy.
AB  - OBJECTIVES: To evaluate the diagnostic efficiency of two-dimensional (2D) and
      three-dimensional (3D) transvaginal ultrasonography, power Doppler angiography
      (PDA) and gel infusion sonography (GIS) at offline analysis for recognition of
      malignant endometrium compared with real-time evaluation during scanning, and to
      determine optimal image parameters at 3D analysis. METHODS: One hundred and sixty
      nine consecutive women with postmenopausal bleeding and endometrial thickness >=
      5 mm underwent systematic evaluation of endometrial pattern on 2D imaging, and 2D
      videoclips and 3D volumes were later analyzed offline. Histopathological findings
      at hysteroscopy or hysterectomy were used as the reference standard. The
      efficiency of the different techniques for diagnosis of malignancy was calculated
      and compared. 3D image parameters, endometrial volume and 3D vascular indices
      were assessed. Optimal 3D image parameters were transformed by logistic
      regression into a risk of endometrial cancer (REC) score, including scores for
      body mass index, endometrial thickness and endometrial morphology at gray-scale
      and PDA and GIS. RESULTS: Offline 2D and 3D analysis were equivalent, but had
      lower diagnostic performance compared with real-time evaluation during scanning.
      Their diagnostic performance was not markedly improved by the addition of PDA or
      GIS, but their efficiency was comparable with that of real-time 2D-GIS in offline
      examinations of good image quality. On logistic regression, the 3D parameters
      from the REC-score system had the highest diagnostic efficiency. The area under
      the curve of the REC-score system at 3D-GIS (0.89) was not improved by inclusion
      of vascular indices or endometrial volume calculations. CONCLUSION: Real-time
      evaluation during scanning is most efficient, but offline 2D and 3D analysis is
      useful for prediction of endometrial cancer when good image quality can be
      obtained. The diagnostic efficiency at 3D analysis may be improved by use of REC
      scoring systems, without the need for calculation of vascular indices or
      endometrial volume. The optimal imaging modality appears to be real-time 2D-GIS.

PMID- 24862862
TI  - Characterization of the mitofusin 2 R94W mutation in a knock-in mouse model.
AB  - Charcot-Marie-Tooth disease (CMT) comprises a group of heterogeneous peripheral
      axonopathies affecting 1 in 2,500 individuals. As mutations in several genes
      cause axonal degeneration in CMT type 2, mutations in mitofusin 2 (MFN2) account
      for approximately 90% of the most severe cases, making it the most common cause
      of inherited peripheral axonal degeneration. MFN2 is an integral mitochondrial
      outer membrane protein that plays a major role in mitochondrial fusion and
      motility; yet the mechanism by which dominant mutations in this protein lead to
      neurodegeneration is still not fully understood. Furthermore, future pre-clinical
      drug trials will be in need of validated rodent models. We have generated a Mfn2
      knock-in mouse model expressing Mfn2(R94W), which was originally identified in
      CMT patients. We have performed behavioral, morphological, and biochemical
      studies to investigate the consequences of this mutation. Homozygous inheritance
      leads to premature death at P1, as well as mitochondrial dysfunction, including
      increased mitochondrial fragmentation in mouse embryonic fibroblasts and
      decreased ATP levels in newborn brains. Mfn2(R94W) heterozygous mice show
      histopathology and age-dependent open-field test abnormalities, which support a
      mild peripheral neuropathy. Although behavior does not mimic the severity of the
      human disease phenotype, this mouse can provide useful tissues for studying
      molecular pathways associated with MFN2 point mutations.

PMID- 24862863
TI  - Label-free fluorescence polarization detection of pyrophosphate based on 0D/1D
      fast transformation of CdTe nanostructures.
AB  - A novel and label-free fluorescence polarization (FP) method for the
      determination of pyrophosphate (PPi) is developed based on the change in FP
      signals during fast reversible transformation between CdTe zero-dimensional (0D)
      nanocrystals (NCs) and one-dimensional (1D) nanorods (NRs) induced by addition of
      PPi. Under optimum conditions, the FP ratio was linearly proportional to the
      logarithm of the concentration of PPi between 2.0 * 10(-5) and 1.0 * 10(-9) M
      with a detection limit of 8.0 * 10(-10) M. The developed method, with high signal
      selectivity and stability, was successfully applied to the detection of PPi in
      human urine samples. 

PMID- 24862865
TI  - Taming living carbocations in catalytic direct conjugate addition of simple
      alkenes to alpha,beta-enones.
AB  - A Lewis acid in the presence of an anionic phosphate ligand enables the addition
      of alkenes to alpha,beta-enones. The ligand facilitates selective beta-proton
      elimination by suppressing competing pathways, thus leading to vinylation adducts
      in high yields (up to 99 %) for a broad range of substrates. 

PMID- 24862864
TI  - L-citrulline provides a novel strategy for treating chronic pulmonary
      hypertension in newborn infants.
AB  - Effective therapies are urgently needed for infants with forms of pulmonary
      hypertension that develop or persist beyond the first week of life. The L
      arginine nitric oxide (NO) precursor, L-citrulline, improves NO signalling and
      ameliorates pulmonary hypertension in newborn animals. In vitro studies
      demonstrate that manipulating L-citrulline transport alters NO production.
      CONCLUSION: Strategies that increase the supply and transport of L-citrulline
      merit pursuit as novel approaches to managing infants with chronic, progressive
      pulmonary hypertension.

PMID- 24862866
TI  - Oestrogen-dependent satellite cell activation and proliferation following a
      running exercise occurs via the PI3K signalling pathway and not IGF-1.
AB  - AIM: The purpose of this study was to determine whether 17beta-estradiol (E2)
      enhances the activation, proliferation and differentiation of muscle satellite
      cells (SC) following eccentric exercise either via insulin-like growth factor-1
      (IGF-1) or through phosphatidylinositol 3-kinase (PI3K) signalling. METHODS: This
      study used 64, 9-week-old, ovariectomized Sprague-Dawley rats that were divided
      into eight treatments groups based on oestrogen status (0.25 mg oestrogen pellet
      or sham), exercise status (90 min run @ 17 m min(-1), -13.5 degrees  or
      unexercised) and PI3K signalling inhibition (0.7 mg wortmannin kg(-1) body weight
      or DMSO control). RESULTS: Significant increases in total SCs were found in both
      soleus and white gastrocnemius muscles (immunofluorescent co-localization of
      Pax7(+) nuclei) 72 h following eccentric exercise (P < 0.05). Oestrogen
      supplementation caused a further enhancement in total SCs in exercised rats (P <
      0.05). In animals where the PI3K pathway was inhibited, regardless of oestrogen
      or exercise status, there was no significant enhancement of SC number in both the
      soleus or white gastrocnemius muscles. Interestingly, oestrogen supplementation
      lowered muscle levels of IGF-1 with this effect being most prominent in the
      soleus muscle. While IGF-1 was increased following exercise (P < 0.05), oestrogen
      supplementation abrogated this increase back to sedentary levels. CONCLUSION:
      These data suggest that the increase in SC population following exercise in
      oestrogen-supplemented females may be mediated via PI3K pathway signalling and
      not IGF-1.

PMID- 24862867
TI  - Effect of high-dose 1.25 dihydroxyvitamin D3 on remyelination in the cuprizone
      model.
AB  - Vitamin D supplementation is increasingly recommended to patients with multiple
      sclerosis (MS). To study the effect of high-dose vitamin D on remyelination,
      female C57Bl/6 mice were demyelinated with dietary 0.2% cuprizone for 7 weeks.
      The mice received intraperitoneal injections of 1.25-dihydroxyvitamin D3
      (calcitriol) or placebo (vehicle) injections twice a week, from week 6,
      throughout week 9. Mice that received calcitriol had initially increased
      demyelination (p = 0.021), astrocytosis (p = 0.043), and microglia activation.
      However, levels of astrocytosis and microglia activation dropped below those of
      the placebo group during the remyelination phase. There was a significant
      increase in myelination in the calcitriol group throughout the remyelination
      phase (p = 0.041), while the remyelination in the placebo group was not
      significant (p = 0.317). After 3 weeks of remyelination, the calcitriol group had
      more myelin than the placebo group (p = 0.001). The calcitriol group had a higher
      density of NOGO-A positive cells throughout the remyelination phase, and the
      number of NOGO-A positive cells was significantly higher in the calcitriol group
      at one week of remyelination (p = 0.019). There were no significant differences
      in extent of T-lymphocyte infiltration. High-dose calcitriol seems to be safe
      regarding remyelination. Our results indicate that this treatment could actually
      promote the repair process, possibly through a stimulating effect on
      oligodendrocyte maturation and astrocyte activation. The potential of calcitriol
      to stimulate the remyelination process should be investigated further in
      functional studies.

PMID- 24862868
TI  - Unilateral areolar sebaceous hyperplasia on nipple scraping sample.

PMID- 24862869
TI  - Biophysical mechanism of the protective effect of blue honeysuckle (Lonicera
      caerulea L. var. kamtschatica Sevast.) polyphenols extracts against lipid
      peroxidation of erythrocyte and lipid membranes.
AB  - The aim of the present research was to determine the effect of blue honeysuckle
      fruit and leaf extracts components on the physical properties of erythrocyte and
      lipid membranes and assess their antioxidant properties. The HPLC analysis showed
      that the extracts are rich in polyphenol anthocyanins in fruits and flavonoids in
      leaves. The results indicate that both extracts have antioxidant activity and
      protect the red blood cell membrane against oxidation induced by UVC irradiation
      and AAPH. The extracts do not induce hemolysis and slightly increase osmotic
      resistance of erythrocytes. The research showed that extracts components are
      incorporated mainly in the external part of the erythrocyte membrane, inducing
      the formation of echinocytes. The values of generalized polarization and
      fluorescence anisotropy indicate that the extracts polyphenols alter the packing
      arrangement of the hydrophilic part of the erythrocyte and lipid membranes,
      without changing the fluidity of the hydrophobic part. The DSC results also show
      that the extract components do not change the main phase transition temperature
      of DPPC membrane. Studies of electric parameters of membranes modified by the
      extracts showed that they slightly stabilize lipid membranes and do not reduce
      their specific resistance or capacity. Examination of IR spectra indicates small
      changes in the degree of hydration in the hydrophilic region of liposomes under
      the action of the extracts. The location of polyphenolic compounds in the
      hydrophilic part of the membrane seems to constitute a protective shield of the
      cell against other substances, the reactive forms of oxygen in particular. 

PMID- 24862871
TI  - Physicochemical aspects of reaction of ozone with galactolipid and galactolipid
      tocopherol layers.
AB  - The impact of reaction of galactolipids with ozone on the physicochemical
      properties of their monolayers was examined. In Megli and Russo (Biochim Biophys
      Acta, 1778:143-152, 2008), Cwiklik and Jungwirth (Chem Phys Lett, 486:99-103,
      2010), Jurkiewicz et al. (Biochim Biophys Acta, 1818:2388-2402, 2012), Khabiri et
      al. (Chem Phys Lett, 519:93-99, 2012), and Conte et al. (Biochim Biophys Acta,
      1828:510-517, 2013), the properties of layers formed from model mixtures composed
      of chosen lipids and selected oxidation products were studied, whereas in this
      work, question was raised as to how the oxidation reactions taking place in situ
      affect the physical properties of the galactolipid layers. So, set experiment
      should take into account the effect of all reaction products. The mechanical
      characteristics of monolayers of monogalactosyldiacyl-glycerol (MGDG) and
      digalactosyldiacylglycerol (DGDG) were determined by Langmuir trough technique,
      and the electrical properties of liposomes formed from these lipids by measuring
      their electrophoretic mobility. Considerable loss of galactolipid molecules
      forming monolayers was found at ozone concentrations (in aqueous medium) higher
      than 0.1 ppm with a stronger effect measured for MGDG. That goes along with the
      greater amounts of MDA found in the extracts of oxidized MGDG films compared with
      DGDG. Based on this, it was concluded that an additional galactose group present
      in DGDG molecules acts protectively under oxidative conditions. The surface
      tension of the solutions (of small volume) contacting the oxidized galactolipids
      films was significantly reduced, indicating the presence of soluble in polar
      media, surface active reaction products. The presence of alpha-tocopherol in
      mixtures with tested galactolipids at a molar ratio of lipid to tocopherol equal
      to 1.7:1 caused some inhibition of lipid oxidation, reducing the decrease of
      amount of lipid particles forming the monolayer. Here, also protective effect of
      alpha-tocopherol was greater for the MGDG compared to DGDG. 

PMID- 24862872
TI  - Cyclin D1 gene amplification is highly homogeneous in breast cancer.
AB  - BACKGROUND: Cyclin D1 (CCND1) gene amplification is a molecular key alteration in
      breast cancer and was suggested to predict resistance to antihormonal therapy. As
      tissue heterogeneity may affect diagnostic accuracy of predictive biomarkers,
      CCND1 genetic heterogeneity was assessed in this study. A novel tissue microarray
      (TMA) platform was manufactured for this purpose. METHODS: Primary breast
      carcinomas from 147 patients were sampled in a "heterogeneity-TMA" by taking
      eight different tissue cores from 4 to 8 tumor-containing blocks per case.
      Additional tissue samples were taken from 1 to 4 corresponding nodal metastases
      in 35 of these patients. CCND1 amplification was assessed by fluorescence in situ
      hybridization (FISH). RESULTS: CCND1 amplification was seen in 28 of 133 (21.05
      %) informative patients. Amplification was significantly associated with high
      tumor grade (p = 0.042), but unrelated to tumor type (p = 0.307), stage (p =
      0.540) and ER (p = 0.061) or PR (p = 0.871) expression. A discordant Cyclin D1
      amplification status was detected in 6 out of 28 (21.43 %) amplified tumors by
      heterogeneity-TMA analysis. Re-testing on large sections revealed three patients
      with true heterogeneity of high-level CCND1 amplification and another three
      patients with variable interpretation of borderline FISH ratios ranging between
      1.7 and 2.3. No discrepancies were detected between 22 primary tumors and their
      matched lymph node metastases. CONCLUSIONS: The high degree of homogeneity seen
      for CCND1 amplification suggests that this alteration is an early event in the
      development of a small subset of breast cancers.

PMID- 24862873
TI  - Influence of surface polarity on water dynamics at the water/rutile TiO2(110)
      interface.
AB  - We report molecular dynamics (MD) simulations of the water/clean rutile TiO2
      (110) interface using polarizable and non-surface polarity force field models.
      The effect of surface polarity on the water dynamics near the TiO2(110) surface
      is addressed, specifically by calculating the water hydrogen bond and
      reorientational dynamics. The hydrogen bond lifetime of interfacial water
      molecules is several times longer than that of bulk water due to the strong water
      TiO2 interactions. A comparison of the dynamics simulated with the polarizable
      and non-surface polarity models shows that, while the hydrogen bond lifetime
      between the interfacial water and TiO2 surface is insensitive to the surface
      polarity, the reorientational dynamics around this hydrogen bond axis is
      significantly influenced by the surface polarity; the surface polarity of the
      TiO2 increases the water-TiO2 interactions, stabilizing the local structure of
      the interfacial water molecules and restricting their rotational motion. This
      reorientation occurs predominantly by rotation around the O-H group hydrogen
      bonded to the TiO2 surface. Furthermore, we correlate the dynamics of the induced
      charge on the TiO2 surface with the interfacial water dynamics. Our results show
      that the timescale of correlations of the atom charges induced by the local
      electric field in bulk water is influenced by the rotational motion, hydrogen
      bond rearrangement and translational motion, while the induced charge dynamics of
      the TiO2 surface is governed primarily by the rotational dynamics of the
      interfacial water molecules. This study demonstrates that the solid surface
      polarity has a significant impact on the dynamics of water molecules near TiO2
      surfaces. 

PMID- 24862870
TI  - Amphipol-trapped ExbB-ExbD membrane protein complex from Escherichia coli: a
      biochemical and structural case study.
AB  - Nutrient import across Gram-negative bacteria's outer membrane is powered by the
      proton-motive force, delivered by the cytoplasmic membrane protein complex ExbB
      ExbD-TonB. Having purified the ExbB4-ExbD2 complex in the detergent dodecyl
      maltoside, we substituted amphipol A8-35 for detergent, forming a water-soluble
      membrane protein/amphipol complex. Properties of the ExbB4-ExbD2 complex in
      detergent or in amphipols were compared by gel electrophoresis, size exclusion
      chromatography, asymmetric flow field-flow fractionation, thermal stability
      assays, and electron microscopy. Bound detergent and fluorescently labeled
      amphipol were assayed quantitatively by 1D NMR and analytical
      ultracentrifugation, respectively. The structural arrangement of ExbB4-ExbD2 was
      examined by EM, small-angle X-ray scattering, and small-angle neutron scattering
      using a deuterated amphipol. The amphipol-trapped ExbB4-ExbD2 complex is slightly
      larger than its detergent-solubilized counterpart. We also investigated a
      different oligomeric form of the two proteins, ExbB6-ExbD4, and propose a
      structural arrangement of its transmembrane alpha-helical domains. 

PMID- 24862874
TI  - Evidence of an environmental effect on survival in ALS.
AB  - Amyotrophic lateral sclerosis (ALS, motor neuron disease) is a neurodegenerative
      disorder of motor neurons leading to paralysis and eventual death by respiratory
      failure. Median survival is 2-3 years. Susceptibility genes, environmental
      triggers and disease related prognostic factors have been established, but
      environmental effects on survival are yet to be investigated. We analysed
      survival in the South-East England ALS register (SEALS register). Kaplan-Meier
      and Cox regression analyses were used to investigate survival in London, coastal
      and rural areas according to postcode at diagnosis. Results showed that there
      were 933 cases of ALS identified in the catchment area during the study period
      (1994-January 2012). Cox regression demonstrated a highly significant model for
      survival with significant protective variables: coastal residency, riluzole use
      and younger age at onset. Significantly worse survival was associated with London
      residency, older age as well as definite and probable El Escorial
      classifications. In conclusion, these findings suggest the possibility of an
      environmental effect on survival in ALS.

PMID- 24862875
TI  - The effect of extending dinoprostone pessary placement from 12 to 24 h on the
      need for further mechanical cervical ripening.
AB  - Dinoprostone pessaries (DP) are widely used for cervical ripening, and while
      licensed for 12-h administration in Australia, 24-h use is also reported. We
      examined 396 consecutive women before and after a protocol change from 12-h to 24
      h DP use to determine whether extended DP use decreases the need for additional
      mechanical cervical ripening. No significant difference in cervical ripening
      balloon (CRB) requirement or vaginal birth rates was detected, showing that
      prolonged DP use does not reduce subsequent use of CRB.

PMID- 24862876
TI  - Endocrinology and art. Orazio Marinali (1643-1720): "Goitrous commoner woman".

PMID- 24862878
TI  - Pretreatment with mineralocorticoid receptor blocker reduces intestinal injury
      induced by ischemia and reperfusion: involvement of inhibition of inflammatory
      response, oxidative stress, nuclear factor kappaB, and inducible nitric oxide
      synthase.
AB  - BACKGROUND: Spironolactone (Sp), a mineralocorticoid receptor antagonist,
      protects against the ischemia reperfusion (IR) injury of retina, kidney, heart,
      and brain. We aimed to investigate the effects of Sp on intestinal IR injury.
      METHODS: Male Wistar rats were randomly divided into: (1) a sham control group;
      (2) an IR control group, subjected to 30 min ischemia and 3 h reperfusion; (3) a
      group treated with Sp (20 mg/kg) for 3 d before the IR; and (4) a sham-operated
      control group treated with Sp (20 mg/kg). After the reperfusion, blood and
      intestinal tissue samples were collected to evaluate histopathologic state,
      neutrophil infiltration (by measuring myeloperoxidase activity), levels of the
      cytokines (tumor necrosis factor alpha, interleukin 1alpha [IL-1alpha],
      interferon gamma, monocyte chemotactic protein-1, granulocyte macrophage-colony
      stimulating factor, and IL-4), malondialdehyde (MDA) and reduced glutathione
      contents, and immunohistochemical expressions of nuclear factor kappaB, inducible
      nitric oxide synthase (iNOS), and caspase-3. RESULTS: MDA content,
      myeloperoxidase activity, and plasma levels of tumor necrosis factor alpha, IL
      1alpha, and monocyte chemotactic protein-1 were all elevated in IR, indicating
      the oxidative stress and local and systemic inflammatory response. Sp
      administration markedly reduced the MDA content and the cytokine levels. The
      pretreatment alleviated intestinal injury, neutrophil infiltration, and the
      expressions of caspase-3, iNOS, and NFkappaB. CONCLUSIONS: The results implicate
      that Sp may have a strong protective effect against the intestinal IR injury. The
      effect can be mediated via suppression of both systemic inflammatory response and
      apoptosis through amelioration of oxidative stress and generation of
      proinflammatory cytokines, iNOS, caspase-3, and nuclear factor kappaB. Therefore,
      mineralocorticoid receptor antagonism might be of potential therapeutic benefit
      in cases of intestinal IR damage.

PMID- 24862877
TI  - Medical treatment in gender dysphoric adolescents endorsed by SIAMS-SIE-SIEDP
      ONIG.
AB  - PURPOSE: Despite international guidelines being available, not all gender clinics
      are able to face gender dysphoric (GD) youth population needs specifically. This
      is particularly true in Italy. Centers offering specialized support are
      relatively few and a commonly accepted Italian approach to GD youth has still not
      been defined. The aim of the present Position Statement is to develop and adhere
      to Italian guidelines for treatment of GD adolescents, in line with the "Dutch
      Approach", the Endocrine Society (ES), and the World Professional Association for
      Transgender Health (WPATH) guidelines. METHODS: An in-depth brainstorming on the
      application of International guidelines in the Italian context was performed by
      several dedicated professionals. RESULTS: A staged approach, combining
      psychological support as well as medical intervention is suggested. In the first
      phase, individuals requesting medical help will undergo a psycho-diagnostic
      procedure to assess GD; for eligible adolescents, pubertal suppression should be
      made available (extended diagnostic phase). Finally, from the age of 16 years,
      cross-sex hormonal therapy can be added, and from the age of 18 years, surgical
      sex reassignment can eventually be performed. CONCLUSIONS: The current inadequacy
      of Italian services offering specialized support for GD youth may lead to
      negative consequences. Omitting or delaying treatment is not a neutral option. In
      fact, some GD adolescents may develop psychiatric problems, suicidality, and
      social marginalization. With access to specialized GD services, emotional
      problems, as well as self-harming behavior, may decrease and general functioning
      may significantly improve. In particular, puberty suppression seems to be
      beneficial for GD adolescents by relieving their acute suffering and distress and
      thus improving their quality of life.

PMID- 24862879
TI  - A novel P700 redox kinetics probe for rapid, non-intrusive and whole-tissue
      determination of photosystem II functionality, and the stoichiometry of the two
      photosystems in vivo.
AB  - We sought a rapid, non-intrusive, whole-tissue measure of the functional
      photosystem II (PS II) content in leaves. Summation of electrons, delivered by a
      single-turnover flash to P700(+) (oxidized PS I primary donor) in continuous
      background far-red light, gave a parameter S in absorbance units after taking
      into account an experimentally determined basal electron flux that affects P700
      redox kinetics. S was linearly correlated with the functional PS II content
      measured by the O(2) yield per single-turnover repetitive flash in Arabidopsis
      thaliana expressing an antisense construct to the PsbO (manganese-stabilizing
      protein in PS II) proteins of PS II (PsbO mutants). The ratio of S to z(max)
      (total PS I content in absorbance units) was comparable to the PS II/PS I
      reaction-center ratio in wild-type A. thaliana and in control Spinacea oleracea.
      Both S and S/z(max) decreased in photoinhibited spinach leaf discs. The whole
      tissue functional PS II content and the PS II/photosystem I (PS I) ratio can be
      non-intrusively monitored by S and S/z(max), respectively, using a quick P700
      absorbance protocol compatible with modern P700 instruments.

PMID- 24862880
TI  - Culture of honour theory and social anxiety: Cross-regional and sex differences
      in relationships among honour-concerns, social anxiety and reactive aggression.
AB  - Consistent with the "flight or fight" model of anxiety, social anxiety may incite
      withdrawal or attack; yet, it is unclear why some socially anxious individuals
      are vulnerable to aggress. It may be that culture impacts tendencies to "fight"
      or "flee" from social threat. Honour cultures, including the American South,
      permit or even promote aggression in response to honour-threats. Thus, social
      anxiety in the South may be more associated with aggression than in non-honour
      cultures. In the current sample, region moderated the relation between social
      anxiety and aggression; social anxiety related positively to reactive (but not
      proactive) aggression among Southerners (n = 285), but not Midwesterners (n =
      258). Participant sex further moderated the relationship, such that it was
      significant only for Southern women. Also, for Southerners, prototypically
      masculine honour-concerns mediated the relationship between social anxiety and
      reactive aggression. Cultural factors may play key roles in aggressive behaviour
      among some socially anxious individuals. 

PMID- 24862881
TI  - An unusual presentation of Kabuki syndrome: clinical overlap with CHARGE
      syndrome.
AB  - Kabuki syndrome is a rare genetic disorder characterized by intellectual
      disability and multiple congenital anomalies, including short stature, peculiar
      facial appearance, skeletal anomalies, a variety of visceral malformations and
      abnormal dermatoglyphic patterns. We describe a case of Kabuki syndrome
      presenting with atypical features, consisting of bilateral microphthalmia,
      coloboma, anal atresia and panhypopituitarism, showing considerable phenotypic
      overlap with CHARGE syndrome. This report demonstrates that clinical follow-up
      and molecular genetic testing can be useful for establishing the correct
      diagnosis. 

PMID- 24862882
TI  - Interstitial deletion 1p36.32 in two brothers with a distinct phenotype-
      overgrowth, macrocephaly and nearly normal intellectual function.
AB  - We report on two adult patients, who both presented with overgrowth and one of
      them additionally with macrocephaly while carrying an 1p36 microdeletion of about
      2.1 Mb. They are full brothers born to unaffected parents. Although both brothers
      attended special schools, they lived independently without a legal guardian and
      were able to succeed in regular jobs. One of the brothers received a professional
      education. Genetic analysis of the parents revealed neither the microdeletion nor
      a cryptical translocation or inversion. We suggest that the recurrent deletion is
      a result of germline mosaicism, a phenomenon reported only once in the context of
      the 1p36 microdeletion syndrome. Our report confirms the recurrence of the
      apparently de novo 1p36 microdeletion due to a likely germline mosaicism of one
      of the parents. Furthermore, it illustrates the possibility of the distinct
      phenotype with a nearly normal intellectual outcome of the 1p36 microdeletion
      syndrome that might be due to the region involved in our patients. 

PMID- 24862884
TI  - Do trauma stomas ever get reversed?
AB  - BACKGROUND: There is a paucity of information about the frequency and timing of
      reversal after stoma creation for trauma. In addition, the barriers to reversal
      faced by those patients are largely unknown. We hypothesize that the rate of
      stoma creation and reversal are low among trauma patients. Additionally, we
      sought to identify patient-related barriers to stoma reversal. STUDY DESIGN:
      Analysis of the California Office of Statewide Health Planning and Development
      patient database, 1995-2010. Inclusion criteria were all trauma patients with
      hollow viscus injury. Exclusion criteria were presence of a stoma at the time of
      injury or death within 48 hours of admission. Patient characteristics studied
      included age, sex, race, Survival Risk Ratio, Charlson Comorbidity Index, and
      insurance status. Kaplan-Meier, logistic regression, and Cox proportional hazard
      analysis were performed to identify predictors of immediate and eventual
      reversal. RESULTS: A total of 35,346 patients had hollow viscus injury, 3,899
      resulted in stoma creation; 249 (6.4%) were reversed during their initial
      hospitalization. After discharge, 41% of patients were reversed at 6 months, 61%
      at 1 year, and 72% at 5 years. Stoma reversals occurred at a different hospital
      from the initial admission 57.1% of the time. Black race was a significant
      predictor for stoma reversal during the initial hospitalization. After the
      initial admission, having insurance increased the likelihood of reversal
      significantly; however, those of black and Hispanic race had a decreased rate.
      CONCLUSIONS: The stoma reversal rate appears to be higher than we hypothesized;
      this is most likely due to the high rate of patient migration between hospitals.
      The factors that posed substantial barriers to reversal after initial admission
      were lack of health insurance and black and Hispanic race/ethnicity.

PMID- 24862885
TI  - Outcomes after pneumonectomy for benign disease: the impact of urgent resection.
AB  - BACKGROUND: Pneumonectomy for benign disease is often complicated by inflammatory
      processes that obscure operative planes. We reviewed our experience to evaluate
      the impact of requiring urgent or emergent pneumonectomy on outcomes. STUDY
      DESIGN: All pneumonectomies for benign conditions from 1997 to 2012 at a single
      institution were retrospectively reviewed. Mortality was assessed using
      multivariable logistic regression that included laterality, age, and surgery
      status, which was emergent if performed within 24 hours of initial evaluation,
      urgent if performed after 24 hours but within the same hospital stay, and
      otherwise elective. RESULTS: Among 42 pneumonectomies, completion pneumonectomy
      after previous ipsilateral lung resection was performed in 14 patients (33%).
      Resection was elective in 22 patients (52%), urgent in 12 (28%), and emergent in
      8 (19%). The most common indication was for necrotic lung (n = 12; 29%). Muscle
      flaps were used in 26 patients (62%). Perioperative mortality for the entire
      cohort was 29% (n = 12) and was significantly higher when surgery was urgent (5
      of 12; 42%) or emergent (5 of 8; 62.5%) compared with elective (2 of 22; 9.1%) (p
      = 0.03). Requiring urgent or emergent surgery remained a significant predictor of
      mortality in multivariable analysis (odds ratio 10.4, p = 0.01). CONCLUSIONS:
      Pneumonectomy for benign disease has significant risk for mortality, particularly
      when not performed electively. Although surgery cannot be planned in the setting
      of trauma or some situations of acute infection, patients known to have
      conditions that are likely to require pneumonectomy should be considered for
      surgery earlier in their disease course, before developing an acute problem that
      requires urgent or emergent resection.

PMID- 24862883
TI  - Liver planning software accurately predicts postoperative liver volume and
      measures early regeneration.
AB  - BACKGROUND: Postoperative or remnant liver volume (RLV) after hepatic resection
      is a critical predictor of perioperative outcomes. This study investigates
      whether the accuracy of liver surgical planning software for predicting
      postoperative RLV and assessing early regeneration. STUDY DESIGN: Patients
      eligible for hepatic resection were approached for participation in the study
      from June 2008 to 2010. All patients underwent cross-sectional imaging (CT or
      MRI) before and early after resection. Planned remnant liver volume (pRLV) (based
      on the planned resection on the preoperative scan) and postoperative actual
      remnant liver volume (aRLV) (determined from early postoperative scan) were
      measured using Scout Liver software (Pathfinder Therapeutics Inc.). Differences
      between pRLV and aRLV were analyzed, controlling for timing of postoperative
      imaging. Measured total liver volume (TLV) was compared with standard equations
      for calculating volume. RESULTS: Sixty-six patients were enrolled in the study
      from June 2008 to June 2010 at 3 treatment centers. Correlation was found between
      pRLV and aRLV (r = 0.941; p < 0.001), which improved when timing of postoperative
      imaging was considered (r = 0.953; p < 0.001). Relative volume deviation from
      pRLV to aRLV stratified cases according to timing of postoperative imaging showed
      evidence of measurable regeneration beginning 5 days after surgery, with
      stabilization at 8 days (p < 0.01). For patients at the upper and lower extremes
      of liver volumes, TLV was poorly estimated using standard equations (up to 50% in
      some cases). CONCLUSIONS: Preoperative virtual planning of future liver remnant
      accurately predicts postoperative volume after hepatic resection. Early
      postoperative liver regeneration is measureable on imaging beginning at 5 days
      after surgery. Measuring TLV directly from CT scans rather than calculating based
      on equations accounts for extremes in TLV.

PMID- 24862886
TI  - Changing surgical trends in young patients with early stage breast cancer, 2003
      to 2010: a report from the National Cancer Data Base.
AB  - BACKGROUND: Young patients with breast cancer represent a unique cohort of
      patients who often have different treatment plans than older patients. We
      hypothesized that the rates of contralateral prophylactic mastectomy (CPM) were
      significantly higher and those of lumpectomy were significantly lower in young
      patients compared with older patients and that this trend persists when adjusting
      for patient, tumor, and facility factors. STUDY DESIGN: We used the National
      Cancer Data Base (NCDB) to study 553,593 patients from all ages with American
      Joint Committee on Cancer (AJCC) stage 0 to II breast tumors, who underwent
      lumpectomy, unilateral mastectomy, or CPM from 2003 to 2010. RESULTS: Over the
      entire cohort, lumpectomy rates decreased from 67.7% in 2003 to 66.4% in 2010 in
      contrast to women 45 years old or less, in whom the lumpectomy rates went from
      61.3% in 2003 to 49.4% in 2010. Unilateral mastectomy went from 28.2% to 23.9%
      and CPM from 4.1% to 9.7% compared with women 45 years old or less, in whom
      unilateral mastectomy rates went from 29.3% to 26.4% and CPM rates from 9.3% to
      26.4%. Age was the most significant factor related to increasing CPM rates: 19.7%
      of women between 41 and 45 years old underwent CPM vs 5.1% of women between 66
      and 70 years old. There was substantial regional variation in surgical procedures
      for young women: lumpectomy rates were lowest in the West and CPM rates were
      highest in the Midwest. Multivariate logistic regression showed that women 45
      years old or younger compared with women more than 45 years who underwent CPM
      were more likely to be Caucasian, treated at an academic/research institution,
      have larger tumors, higher grade, higher stage, and lobular histology.
      CONCLUSIONS: The rate of CPM continues to increase, with one-quarter of younger
      women undergoing CPM. This trend persists across all patient, tumor, and facility
      characteristics.

PMID- 24862887
TI  - Nonoperative management of main pancreatic duct-involved intraductal papillary
      mucinous neoplasm might be indicated in select patients.
AB  - BACKGROUND: Although the natural history of intraductal papillary mucinous
      neoplasm (IPMN) remains unclear, large surgical series have reported malignancy
      in 40% to 90% of main pancreatic duct (MPD)-involved IPMN. Accordingly, the 2012
      International Consensus Guidelines recommend surgical resection in patients with
      suspected MPD involvement. We hypothesized that nonoperative management of select
      patients with suspected MPD-involved IPMN might be indicated. STUDY DESIGN: From
      1992 to 2012, 362 patients underwent surgical resection for pathologically
      confirmed IPMN at a single academic center. A retrospective review of
      prospectively collected data was performed. Main pancreatic duct involvement was
      suspected with an MPD diameter >=5 mm on preoperative imaging. A multivariate
      analysis was conducted to assess predictors of malignancy. RESULTS: Of 362
      patients, 334 had complete data for analysis. Main pancreatic duct involvement
      was suspected preoperatively in 171 patients. Final pathology revealed 20% high
      grade dysplastic and 27% invasive IPMN (47% malignant). Preoperative
      cytopathology and serum carbohydrate antigen 19-9 independently predicted
      malignancy (p = 0.003 and p = 0.002, respectively) and invasiveness (p < 0.0001
      and p = 0.001, respectively). Patients with both negative preoperative
      cytopathology and normal serum carbohydrate antigen 19-9 (ie, double negatives)
      had a lower rate of malignancy and invasiveness (28% and 8% vs 58% and 38%; p <
      0.0001). The MPD diameter did not predict malignancy or invasiveness (p = 0.36
      and p = 0.46, respectively). CONCLUSIONS: Patients with suspected MPD-involved
      IPMN have a highly variable rate of malignancy. Despite recent International
      Consensus Guidelines recommendations, these data suggest that MPD diameter is not
      an optimal gauge of malignant risk. Nonoperative management of suspected MPD
      involved IPMN in select patients, particularly double negatives, might be
      indicated. Depending on age and comorbidity, operative risk might outweigh the
      risk of malignant progression in these patients.

PMID- 24862888
TI  - Reoperative surgery: a critical risk factor for complications inadequately
      captured by operative reporting and coding of lysis of adhesions.
AB  - BACKGROUND: Reoperative surgery is suspected, but not proven, to increase
      postoperative complication rates. In the absence of a specific definition for
      reoperative surgery, the American College of Surgeons NSQIP has proposed using
      procedural coding for lysis of adhesions (LOA) as a surrogate for reoperative
      surgery to risk adjust hospitals. We hypothesized that coding of reoperative
      surgery will be associated with worse 30-day outcomes and, for abdominal
      procedures, will be more accurate than operative dictation and coding of "lysis
      of adhesions." STUDY DESIGN: Reoperative surgery was categorized at the time of
      data abstraction from February 2012 to December 2012 for all NSQIP cases
      collected at a single institution by independent surgical clinical reviewers.
      Reoperative surgery classification and coding of LOA were compared with each
      other and with 30-day outcomes. The setting was a tertiary cancer center,
      multispecialty NSQIP model. During the study period, 1,289 operations were
      classified as nonreoperative (n = 793), regionally reoperative (n = 39; prior
      surgery in an adjacent area of current operation), or locally reoperative (n =
      457; prior surgery at same site or organ). RESULTS: In the multispecialty cohort,
      the non-risk-adjusted rates of overall 30-day morbidity, serious morbidity, and
      mortality were 21.5%, 17.7%, and 0.5%. Compared with nonreoperative surgery
      (overall 30-day morbidity 16.8%, serious morbidity 13.9%, and mortality .38%),
      both regionally reoperative surgery (overall 30-day morbidity 30.8%, serious
      morbidity 28.2%, and mortality 2.5%) and locally reoperative surgery (overall 30
      day morbidity 28.9%, serious morbidity 23.4%, and mortality .66%) were associated
      with worse outcomes (p < 0.001). One hundred ninety-nine of the 327
      gastrointestinal/laparotomy cases were recorded as reoperative, but only of 20 of
      these were CPT coded as LOA (sensitivity = 10%). CONCLUSIONS: Reoperative surgery
      is frequent, increases the risk of complications, and can be captured. Operative
      LOA coding vastly under reports reoperative surgery and, therefore, is not an
      adequate surrogate for this important risk factor.

PMID- 24862889
TI  - Impact of MCP-1 in atherosclerosis.
AB  - Monocyte chemotactic protein-1 (MCP-1) (also referred to as chemokine (C-C motif)
      ligand 2 (CCL2) is expressed by mainly inflammatory cells and endothelial cells.
      The expression level is upregulated after proinflammatory stimuli and tissue
      injury which are associated with atherosclerotic lesion. Atherosclerosis is a
      progressive disease starting with accumulation of lipids, lipoproteins, and
      immune cells in the arterial wall. MCP-1 has been reported to play an important
      role in the pathogenesis of atherosclerosis and considerable evidence supports
      that the monocyte containing MCPs and macrophage influences the growth of other
      cell types within the atherosclerotic lesion. This review will focus on the
      general structure features of MCP-1 and its role in atherosclerosis. 

PMID- 24862890
TI  - Nitrogen-doped aligned carbon nanotube/graphene sandwiches: facile catalytic
      growth on bifunctional natural catalysts and their applications as scaffolds for
      high-rate lithium-sulfur batteries.
AB  - Nitrogen-doped aligned CNT/graphene sandwiches are rationally designed and in
      situ fabricated by a facile catalytic growth on bifunctional natural catalysts
      that exhibit high-rate performances as scaffolds for lithium-sulfur batteries,
      with a high initial capacity of 1152 mA h g(-1) at 1.0 C. A remarkable capacity
      of 770 mA h g(-1) can be achieved at 5.0 C. Such a design strategy for materials
      opens up new perspectives to novel advanced functional composites, especially
      interface-modified hierarchical nanocarbons for broad applications.

PMID- 24862891
TI  - Physician and patient willingness to pay for electronic cardiovascular disease
      management.
AB  - OBJECTIVES: Cardiovascular disease (CVD) is an important target for electronic
      decision support. We examined the potential sustainability of an electronic CVD
      management program using a discrete choice experiment (DCE). Our objective was to
      estimate physician and patient willingness-to-pay (WTP) for the current and
      enhanced programs. METHODS: Focus groups, expert input and literature searches
      decided the attributes to be evaluated for the physician and patient DCEs, which
      were carried out using a Web-based program. Hierarchical Bayes analysis estimated
      preference coefficients for each respondent and latent class analysis segmented
      each sample. Simulations were used to estimate WTP for each of the attributes
      individually and for an enhanced vascular management system. RESULTS: 144
      participants (70 physicians, 74 patients) completed the DCE. Overall, access
      speed to updated records and monthly payments for a nurse coordinator were the
      main determinants of physician choices. Two distinctly different segments of
      physicians were identified - one very sensitive to monthly subscription fee and
      speed of updating the tracker with new patient data and the other very sensitive
      to the monthly cost of the nurse coordinator and government billing incentives.
      Patient choices were most significantly influenced by the yearly subscription
      cost. The estimated physician WTP was slightly above the estimated threshold for
      sustainability while the patient WTP was below. CONCLUSION: Current willingness
      to pay for electronic cardiovascular disease management should encourage
      innovation to provide economies of scale in program development, delivery and
      maintenance to meet sustainability thresholds.

PMID- 24862892
TI  - Serious Arabic meaning, grammatical, and study design flaws in the study "Faxed
      Arabic Prescriptions: a medication error waiting to happen?".

PMID- 24862893
TI  - Evidence-based management of ambulatory electronic health record system
      implementation: an assessment of conceptual support and qualitative evidence.
AB  - OBJECTIVES: While electronic health record (EHR) systems have potential to drive
      improvements in healthcare, a majority of EHR implementations fall short of
      expectations. Shortcomings in implementations are often due to organizational
      issues around the implementation process rather than technological problems.
      Evidence from both the information technology and healthcare management
      literature can be applied to improve the likelihood of implementation success,
      but the translation of this evidence into practice has not been widespread. Our
      objective was to comprehensively study and synthesize best practices for managing
      ambulatory EHR system implementation in healthcare organizations, highlighting
      applicable management theories and successful strategies. METHODS: We held 45
      interviews with key informants in six U.S. healthcare organizations purposively
      selected based on reported success with ambulatory EHR implementation. We also
      conducted six focus groups comprised of 37 physicians. Interview and focus group
      transcripts were analyzed using both deductive and inductive methods to answer
      research questions and explore emergent themes. RESULTS: We suggest that
      successful management of ambulatory EHR implementation can be guided by the Plan
      Do-Study-Act (PDSA) quality improvement (QI) model. While participants did not
      acknowledge nor emphasize use of this model, we found evidence that successful
      implementation practices could be framed using the PDSA model. Additionally,
      successful sites had three strategies in common: 1) use of evidence from
      published health information technology (HIT) literature emphasizing
      implementation facilitators; 2) focusing on workflow; and 3) incorporating
      critical management factors that facilitate implementation. CONCLUSIONS:
      Organizations seeking to improve ambulatory EHR implementation processes can use
      frameworks such as the PDSA QI model to guide efforts and provide a means to
      formally accommodate new evidence over time. Implementing formal management
      strategies and incorporating new evidence through the PDSA model is a key element
      of evidence-based management and a crucial way for organizations to position
      themselves to proactively address implementation and use challenges before they
      are exacerbated.

PMID- 24862894
TI  - Rapid identification of Streptomyces isolates by MALDI-TOF MS.
AB  - The recent emergence of multidrug-resistant bacteria over the last decade has led
      to a renewal in the discovery of new antimicrobial drugs. Streptomyces members
      are practically unlimited sources of new antibiotics. However, the identification
      of Streptomyces species is difficult and time-consuming. Therefore, there is a
      need for alternative methods for their rapid identification. In this study, an
      efficient protocol of identification using Matrix-Assisted Laser Desorption
      Ionization Time-Of-Flight Mass Spectrometry (MALDI-TOF MS) was developed and
      applied for the rapid identification of Streptomyces isolates from the El Kala
      lakes in northeastern Algeria. A collection of 48 Streptomyces isolates were used
      for this study. The optimized procedure allowed us to obtain specific and
      reproducible protein spectra for each Streptomyces isolate tested. The spectra
      generated were used to build a preliminary local database based on their initial
      16S rRNA identification. The blind test used for the identification of 20
      Streptomyces strains already available in our created database and 20 unknown
      Streptomyces isolates showed that all (100%) of the Streptomyces strains listed
      in the database were rapidly (<30min) identified with high scores of up to 2.8.
      Here, for the first time we showed that MALDI-TOF MS could be used as a cost
      effective tool for the rapid identification of Streptomyces isolates. 

PMID- 24862895
TI  - Paroxysmal hypnogenic dyskinesia.

PMID- 24862896
TI  - Bilingualism delays age at onset of dementia, independent of education and
      immigration status.
AB  - Editors' Note: Mortimer argues that important confounding variables may have
      biased the conclusion by Alladi et al. on the role of bilingualism in delaying
      the onset of dementia. Following Mortimer's comments, Alladi et al. conducted
      additional analysis of their data to support their conclusion. The attitude of
      "close enough" is not appropriate when determining brain death. Stadlan comments
      and supports Frank's call for action regarding this sensitive issue.

PMID- 24862897
TI  - Practice variability in brain death determination: a call to action.

PMID- 24862898
TI  - Mystery case: Injuries of neural tracts in the Papez circuit following anterior
      thalamic infarction.

PMID- 24862899
TI  - Emerging subspecialties in neurology: neuropalliative care.

PMID- 24862900
TI  - Teaching NeuroImages: leptomeningeal lung carcinoma.

PMID- 24862901
TI  - Patient page. New evidence for reduced leg oxygen levels in restless legs
      syndrome.

PMID- 24862902
TI  - Design of synthetic yeast promoters via tuning of nucleosome architecture.
AB  - Model-based design of biological parts is a critical goal of synthetic biology,
      especially for eukaryotes. Here we demonstrate that nucleosome architecture can
      have a role in defining yeast promoter activity and utilize a computationally
      guided approach that can enable both the redesign of endogenous promoter
      sequences and the de novo design of synthetic promoters. Initially, we use our
      approach to reprogram native promoters for increased expression and evaluate
      their performance in various genetic contexts. Increases in expression ranging
      from 1.5- to nearly 6-fold in a plasmid-based system and up to 16-fold in a
      genomic context were obtained. Next, we demonstrate that, in a single design
      cycle, it is possible to create functional, purely synthetic yeast promoters that
      achieve substantial expression levels (within the top sixth percentile among
      native yeast promoters). In doing so, this work establishes a unique DNA-level
      specification of promoter activity and demonstrates predictive design of
      synthetic parts. 

PMID- 24862903
TI  - The role of pattern recognition in children's exact enumeration of small numbers.
AB  - Enumeration can be accomplished by subitizing, counting, estimation, and
      combinations of these processes. We investigated whether the dissociation between
      subitizing and counting can be observed in 4- to 6-year-olds and studied whether
      the maximum number of elements that can be subitized changes with age. To detect
      a dissociation between subitizing and counting, it is tested whether task
      manipulations have different effects in the subitizing than in the counting
      range. Task manipulations concerned duration of presentation of elements
      (limited, unlimited) and configuration of elements (random, line, dice). In Study
      1, forty-nine 4- and 5-year-olds were tested with a computerized enumeration
      task. Study 2 concerned data from 4-, 5-, and 6-year-olds, collected with Math
      Garden, a computer-adaptive application to practice math. Both task manipulations
      affected performance in the counting, but not the subitizing range, supporting
      the conclusion that children use two distinct enumeration processes in the two
      ranges. In all age groups, the maximum number of elements that could be subitized
      was three. The strong effect of configuration of elements suggests that
      subitizing might be based on a general ability of pattern recognition. 

PMID- 24862905
TI  - Poly(2-hydroxyethyl methacrylate)-b-poly(L-Lysine) cationic hybrid materials for
      non-viral gene delivery in NIH 3T3 mouse embryonic fibroblasts.
AB  - In order to develop efficient and nontoxic gene delivery vectors, a series of
      biocompatible block copolymers, poly[(2-hydroxyethyl methacrylate)40 -block-(L
      lysine)n ] (n = 40, 80, 120, 150), are prepared by combining an atom transfer
      radical polymerization of 2-hydroxyethyl methacrylate with a ring-opening
      polymerization of N(epsilon) -(carbobenzoxy)-L-lysine N-carboxyanhydride. The
      block copolymers are successfully condensed with plasmid DNA (pDNA) into
      nanosized (<200 nm) polyplexes. As a representative sample, p(HEMA)40 -b
      p(lys)150 is utilized to confirm the effective cellular and nuclear uptake of
      pDNA. The polymer/pDNA polyplexes exhibit very low cytotoxicity and enhanced
      transfection activity by being easily taken up into mouse embryonic fibroblast
      cell line (NIH 3T3). Thus, the chimeric block copolymers provide a means for
      developing versatile nonviral gene vectors harboring the ideal requirements of
      low cytotoxicity, good stability, and high transfection efficiency for gene
      therapy. 

PMID- 24862906
TI  - The impact of nonsustained ventricular tachycardia on reverse remodeling, heart
      failure, and treated ventricular tachyarrhythmias in MADIT-CRT.
AB  - INTRODUCTION: This study determined whether the presence of nonsustained
      ventricular tachycardia (NSVT) was predictive of clinical events in MADIT-CRT
      (multicenter automatic defibrillator implantation trial-cardiac resynchronization
      therapy) patients treated with CRT-defibrillator. METHODS AND RESULTS: We
      analyzed 24-hour Holters for the presence of NSVT. Patients were then stratified
      by the etiology (ischemic or nonischemic) of cardiomyopathy. The impact of NSVT
      on heart failure events (HF), implantable cardioverter-defibrillator (ICD)
      therapy for rapid ventricular tachycardia (VT) or fibrillation (VF), and reverse
      remodeling was determined. At least a single episode of NSVT was recorded in 483
      (49%) patients. These patients had a higher burden of premature ventricular
      contractions, lower percentage of biventricular (BiV) pacing, and significantly
      less reduction in left ventricular end-diastolic and end-systolic volumes. The
      risk of HF was significantly greater in patients with nonischemic cardiomyopathy
      and NSVT (hazard ratio [HR] 2.89; 95% confidence interval [CI]: 1.49-5.61; P =
      0.002). The risk of rapid VT/VF was significantly greater (in both ischemic and
      nonischemic patients) when NSVT was observed (HR 2.06; 95% CI: 1.30-3.26; P =
      0.002 in ischemic patients; HR 3.09; 95% CI: 1.80-5.28; P < 0.001 in nonischemic
      patients). CONCLUSIONS: MADIT-CRT patients with NSVT had a high burden of
      ventricular ectopy, lower percentage of BiV pacing, and less reverse remodeling.
      These patients had an increase in HF (in nonischemic cardiomyopathy patients) and
      rapid VT/VF ICD therapies (in ischemic and nonischemic patients). These findings
      may have implications for the management of nonsustained ventricular ectopy in
      CRT patients.

PMID- 24862907
TI  - Novel product chemistry from mechanistic analysis of ent-copalyl diphosphate
      synthases from plant hormone biosynthesis.
AB  - An active-site water molecule coordinated by conserved histidine and asparagine
      residues seems to serve as the catalytic base in all ent-copalyl diphosphate
      synthases (CPSs). When these residues are substituted by alanine, the mutant CPSs
      produce stereochemically novel ent-8-hydroxy-CPP. Given the requisite presence of
      CPSs in all land plants for gibberellin phytohormone biosynthesis, such
      plasticity presumably underlies the observed extensive diversification of the
      resulting labdane-related diterpenoids. 

PMID- 24862908
TI  - Inbred mouse strains reveal biomarkers that are pro-longevity, antilongevity or
      role switching.
AB  - Traditionally, biomarkers of aging are classified as either pro-longevity or
      antilongevity. Using longitudinal data sets from the large-scale inbred mouse
      strain study at the Jackson Laboratory Nathan Shock Center, we describe a
      protocol to identify two kinds of biomarkers: those with prognostic implication
      for lifespan and those with longitudinal evidence. Our protocol also identifies
      biomarkers for which, at first sight, there is conflicting evidence. Conflict
      resolution is possible by postulating a role switch. In these cases, high
      biomarker values are, for example, antilongevity in early life and pro-longevity
      in later life. Role-switching biomarkers correspond to features that must, for
      example, be minimized early, but maximized later, for optimal longevity. The
      clear-cut pro-longevity biomarkers we found reflect anti-inflammatory, anti
      immunosenescent or anti-anaemic mechanisms, whereas clear-cut antilongevity
      biomarkers reflect inflammatory mechanisms. Many highly significant blood
      biomarkers relate to immune system features, indicating a shift from adaptive to
      innate processes, whereas most role-switching biomarkers relate to blood serum
      features and whole-body phenotypes. Our biomarker classification approach is
      applicable to any combination of longitudinal studies with life expectancy data,
      and it provides insights beyond a simplified scheme of biomarkers for long or
      short lifespan. 

PMID- 24862904
TI  - The impact of leptin on perinatal development and psychopathology.
AB  - Leptin has long been associated with metabolism as it is a critical regulator of
      both food intake and energy expenditure, but recently, leptin dysregulation has
      been proposed as a mechanism of psychopathology. This review discusses the
      evidence supporting a role for leptin in mental health disorders and describes
      potential mechanisms that may underlie this association. Leptin plays a critical
      role in pregnancy and in fetal growth and development. Leptin's role and profile
      during development is examined in available human studies, and the validity of
      applying studies conducted in animal models to the human population are
      discussed. Rodents experience a postnatal leptin surge, which does not occur in
      humans or larger animal models. This suggests that further research using large
      mammal models, which have a leptin profile across pregnancy and development
      similar to humans, are of high importance. Maternal obesity and hyperleptinemia
      correlate with increased leptin levels in the umbilical cord, placenta, and
      fetus. Leptin levels are thought to impact fetal brain development; likely by
      activating proinflammatory cytokines that are known to impact many of the
      neurotransmitter systems that regulate behavior. Leptin is likely involved in
      behavioral regulation as leptin receptors are widely distributed in the brain,
      and leptin influences cortisol release, the mesoaccumbens dopamine pathway,
      serotonin synthesis, and hippocampal synaptic plasticity. In humans, both high
      and low levels of leptin are reported to be associated with psychopathology. This
      inconsistency is likely due to differences in the metabolic state of the study
      populations. Leptin resistance, which occurs in the obese state, may explain how
      both high and low levels of leptin are associated with psychopathology, as well
      as the comorbidity of obesity with numerous mental illnesses. Leptin resistance
      is likely to influence disorders such as depression and anxiety where high leptin
      levels have been correlated with symptomatology. Schizophrenia is also associated
      with both low and high leptin levels. However, as anti-psychotics pharmacotherapy
      induces weight gain, which elevates leptin levels, drug-naive populations are
      needed for further studies. Elevated circulating leptin is consistently found in
      childhood neurodevelopmental disorders including autism spectrum disorders and
      Rhett disorder. Further, studies on the impact of leptin and leptin resistance on
      psychopathology and neurodevelopmental disorders are important directions for
      future research. Studies examining the mechanisms by which exposure to maternal
      obesity and hyperleptinemia during fetal development impact brain development and
      behavior are critical for the health of future generations. 

PMID- 24862909
TI  - Health literacy and its association with perception of teratogenic risks and
      health behavior during pregnancy.
AB  - OBJECTIVE: Investigate the association between health literacy and perception of
      medication risk, beliefs about medications, use and non-adherence to prescribed
      pharmacotherapy during pregnancy, and whether risk perception and beliefs may
      mediate an association between health literacy and non-adherence. METHODS: This
      multinational, cross-sectional, internet-based study recruited pregnant woman
      between 1 October 2011 and 29 February 2012. Data on maternal socio-demographics,
      medication use, risk perception, beliefs, and non-adherence were collected via an
      on-line questionnaire. Health literacy was measured via a self-assessment scale.
      Mann-Whitney U test, Spearman's rank correlation, Generalized Estimating
      Equations and mediation analysis were utilized. RESULTS: 4999 pregnant women were
      included. Low-health literacy women reported higher risk perception for
      medications, especially penicillins (Rho: -0.216) and swine flu vaccine (Rho: 
      0.204) and more negative beliefs about medication. Non-adherence ranged from
      19.2% (high-health literacy) to 25.0% (low-health literacy). Low-health literacy
      women were more likely to be non-adherent to pharmacotherapy than their high
      level counterparts (adjusted OR: 1.30; 95% CI: 1.02-1.66). Risk perception and
      beliefs appeared to mediate the association between health literacy and non
      adherence. CONCLUSION: Health literacy was significantly associated with maternal
      health behaviors regarding medication non-adherence. PRACTICE IMPLICATIONS:
      Clinicians should take time to inquire into their patients' ability to understand
      health information, perception and beliefs, in order to promote adherence during
      pregnancy.

PMID- 24862910
TI  - Predicting cancer patients' participation in support groups: a longitudinal
      study.
AB  - OBJECTIVE: Few patients participate in cancer support groups despite their
      benefits. This study investigated the importance of Theory of Planned Behaviour
      variables in predicting group participation, relative to disease impact, existing
      support, coping and demographic variables. METHODS: Longitudinal study of
      patients with colorectal, lung or prostate cancer recruited from a specialist
      oncology centre. Patients self-completed surveys at baseline and six-month follow
      up. Baseline measures included Theory of Planned Behaviour (TPB) variables,
      distress and control over cancer (IPQ-R), coping (Brief COPE), social support
      (MSPSS), health related quality of life (EORTC QLQ-C30) and readiness to
      participate (PAPM). Group participation and recommendations to participate were
      measured at follow up. Univariable and Random Forest analyses investigated
      predictors of baseline readiness to participate and participation by six-month
      follow up. RESULTS: N=192 patients completed baseline questionnaires. N=13
      participated in a group and N=59 did not by six-month follow up. Baseline
      readiness to participate was associated with inadequate support and positive
      views of support groups. Lower cognitive functioning, recommendations and
      readiness to participate predicted group participation by six-month follow up.
      CONCLUSION AND PRACTICE IMPLICATIONS: Practitioners may facilitate group
      participation by promoting positive views of groups, recommending participation
      and focusing on patients experiencing greater disease impact and less existing
      support.

PMID- 24862911
TI  - Patient perspectives of patient-centeredness in medical rehabilitation.
AB  - OBJECTIVE: Achieving patient-centeredness requires a paradigm shift in the
      provider-patient interaction. Participation, information, communication, and
      interaction are essential indicators in this area. The study examined the
      evaluation and implementation of indicators of patient-centeredness for
      chronically ill patients and center-specific differences in this regard. METHODS:
      This cross-sectional study with mixed-method design combined focus groups and a
      questionnaire survey at 5 rehabilitation centers. The analysis included a
      qualitative component with summarizing content analysis and a descriptive
      exploratory quantitative component. RESULTS: Patients (N=32) rated the indicators
      of patient-centeredness favorably to very favorably (on a scale of 1=very good to
      6=unsatisfactory). The centers exhibited significant differences in "patient
      participation" (p<.05). Dominant topics voiced in the focus groups were the
      desire for more individualized treatment (n=30) and more specific and rapid
      feedback on treatment goals (n=13). CONCLUSION: Considerable between-center
      differences exist, particularly in patients' opportunity to participate in
      treatment planning, which can be a starting point for improvements. PRACTICE
      IMPLICATIONS: Rehabilitation centers should ask patients to evaluate indicators
      of patient-centeredness and develop targeted actions for improvement. The patient
      survey shows that patients would like improvements in patient-centeredness in the
      overall rehabilitation system, particularly regarding patient participation, and
      training in this area is recommended.

PMID- 24862912
TI  - The experience of people with lung cancer with a volunteer-based lay navigation
      intervention at an outpatient cancer center.
AB  - OBJECTIVE: To describe the experiences of patients with lung cancer with a
      volunteer-based lay navigation intervention. METHODS: Forty patients with newly
      diagnosed lung cancer enrolled in a three-step navigation intervention delivered
      by trained volunteer lay navigators (VLNs), beginning prior to their first
      oncologist's appointment and ending before the start of treatment. Methodological
      triangulation of data was used in a mixed method study design. Cases were
      categorized based on the predominant needs met by the VLN: emotional,
      practical/informational, family, and complex. Data were analyzed using framework
      analysis. RESULTS: The provision of emotional support, information, and referrals
      to other services by the VLN were of particular benefit to the patient and their
      families. Satisfaction with the program and its timing was high; it was
      considered an effective means for patients to share concerns and have their needs
      attended to before starting treatment. CONCLUSION: This study demonstrates
      capacity for lay volunteers to address the multifaceted needs of lung cancer
      patients during their transition from primary care in the diagnosis to treatment
      phase. PRACTICE IMPLICATIONS: Using volunteers as navigators offers an
      opportunity to meet patient needs with minimal resources, increase access to
      services for patients, and improve the sustainability of the program.

PMID- 24862914
TI  - Mitral valve repair in a patient with an anomalous left coronary artery.
AB  - Anomalous coronary arteries may course in close proximity to the mitral annulus,
      which increases the risk of iatrogenic occlusion due to annular suture placement.
      We report a mitral valve repair in a 55-year-old male with severe mitral
      regurgitation and an anomalous retro-aortic left coronary artery, originating
      from the right coronary sinus, coursing in close proximity to the anterior mitral
      annulus. To minimize iatrogenic occlusion risk an open annuloplasty ring was used
      with good long-term results.

PMID- 24862913
TI  - "Speaking-for" and "speaking-as": pseudo-surrogacy in physician-patient-companion
      medical encounters about advanced cancer.
AB  - OBJECTIVE: To examine using audio-recorded encounters the extent and process of
      companion participation when discussing treatment choices and prognosis in the
      context of a life-limiting cancer diagnosis. METHODS: Qualitative analysis of
      transcribed outpatient visits between 17 oncologists, 49 patients with advanced
      cancer, and 34 companions. RESULTS: 46 qualifying companion statements were
      collected from a total of 28 conversations about treatment choices or prognosis.
      We identified a range of companion positions, from "pseudo-surrogacy" (companion
      speaking as if the patient were not able to speak for himself), "hearsay",
      "conflation of thoughts", "co-experiencing", "observation as an outsider", and
      "facilitation". Statements made by companions were infrequently directly
      validated by the patient. CONCLUSION: Companions often spoke on behalf of
      patients during discussions of prognosis and treatment choices, even when the
      patient was present and capable of speaking on his or her own behalf. PRACTICE
      IMPLICATIONS: The conversational role of companions as well as whether the
      physician checks with the patient can determine whether a companion facilitates
      or inhibits patient autonomy and involvement. Physicians can reduce ambiguity and
      encourage patient participation by being aware of when and how companions may
      speak on behalf of patients and by corroborating the companion's statement with
      the patient.

PMID- 24862915
TI  - Nursing students' prosocial motivation: does it predict professional commitment
      and involvement in the job?
AB  - AIM: This study investigated how prosocial motivation reported by nursing
      students in their final year of academic studies relates to career commitment and
      job involvement three years after graduation. BACKGROUND: Most studies
      investigating nurses' prosocial motivation for choosing the nursing profession
      examine only their prosocial motivation for entering nursing training; they do
      not investigate whether this motivation is associated with job involvement or
      commitment to the profession. DESIGN: A longitudinal survey design was used.
      METHOD: The present longitudinal study included 160 nurses. In their final
      academic year of spring 2007, the nurses received a questionnaire about their
      motivation for entering nursing. Three years after graduation, spring 2010, they
      received another questionnaire about their level of job involvement and career
      commitment. RESULTS: The results showed that prosocial motivation measured in
      their last academic year was related to career commitment three years after
      graduation, but unrelated to job involvement. CONCLUSION: The results indicated
      that prosocial motivation is important in identifying with the profession but not
      necessarily for personal involvement in the job. The study gives important
      knowledge on how a commonly reported motivation for entering nursing relates to
      the nurses' attitudes about their work life.

PMID- 24862917
TI  - Tool value: the liver donor risk index 8 years on.

PMID- 24862916
TI  - Merkel cells and touch domes: more than mechanosensory functions?
AB  - The touch dome (TD) is an innervated structure in the epidermis of mammalian
      skin. Composed of specialized keratinocytes and neuroendocrine Merkel cells, the
      TD has distinct molecular characteristics compared to the surrounding epidermal
      keratinocytes. Much of the research on Merkel cell function has focused on their
      role in mechanosensation, specifically light touch. Recently, more has been
      discovered about Merkel cell molecular characteristics and their cells of origin.
      Here we review Merkel cell and TD biology, and discuss potential functions beyond
      mechanosensation. 

PMID- 24862918
TI  - Serum estradiol level change after human chorionic gonadotropin administration
      had no correlation with live birth rate in IVF cycles.
AB  - OBJECTIVE: To investigate the correlation between the estradiol (E2) level change
      after hCG administration and the live birth rate in GnRH agonist long or short
      protocols, and to explore the possible factors related to E2 dynamics after hCG
      administration during controlled ovarian hyperstimulation (COH). STUDY DESIGN: A
      retrospective analysis was performed on 2868 patients who received
      IVF/intracytoplasmic sperm injection (ICSI) treatment with GnRH agonist long or
      short protocol. The patients were divided into three groups according to their
      serum E2 changes after hCG administration, and the live birth rates were compared
      among groups. The area under the receiver operating characteristic (ROC) curve
      was calculated to assess the predictive value of E2 change for the probability of
      live birth. Logistic regression analysis was also applied to exclude interference
      from various confounding factors. Finally, multivariate regression analysis was
      conducted to assess factors related to the E2 change after hCG administration.
      RESULTS: No significant difference was observed in live birth rates (4.26%,
      36.38% or 30.81% in long protocol (P=0.697); 25.81%, 26.71% or 30.81% in short
      protocol (P=0.697)) among patients with increasing, plateauing or decreasing E2
      responses after hCG administration. The area under the ROC curve for the E2
      change in prediction of live birth rate was 0.506 in long protocol, or 0.524 in
      short protocol. Logistic regression analysis showed that the serum E2 change
      after hCG administration had no correlation with live birth rate. Multivariate
      regression analysis showed that the percentage of mature follicles (larger than
      14mm) and the duration of stimulation negatively correlated with the E2 change
      after hCG administration. CONCLUSIONS: In GnRH agonist cycles, the serum E2
      change after hCG administration had no correlation with live birth rate in fresh
      embryo transfer cycles, and this change negatively correlated with the percentage
      of mature follicles on the day of hCG administration.

PMID- 24862920
TI  - Replacement of a terminal cytochrome c oxidase by ubiquinol oxidase during the
      evolution of acetic acid bacteria.
AB  - The bacterial aerobic respiratory chain has a terminal oxidase of the heme-copper
      oxidase superfamily, comprised of cytochrome c oxidase (COX) and ubiquinol
      oxidase (UOX); UOX evolved from COX. Acetobacter pasteurianus, an alpha
      Proteobacterial acetic acid bacterium (AAB), produces UOX but not COX, although
      it has a partial COX gene cluster, ctaBD and ctaA, in addition to the UOX operon
      cyaBACD. We expressed ctaB and ctaA genes of A. pasteurianus in Escherichia coli
      and demonstrated their function as heme O and heme A synthases. We also found
      that the absence of ctaD function is likely due to accumulated mutations. These
      COX genes are closely related to other alpha-Proteobacterial COX proteins.
      However, the UOX operons of AAB are closely related to those of the beta/gamma
      Proteobacteria (gamma-type UOX), distinct from the alpha/beta-Proteobacterial
      proteins (alpha-type UOX), but different from the other gamma-type UOX proteins
      by the absence of the cyoE heme O synthase. Thus, we suggest that A. pasteurianus
      has a functional gamma-type UOX but has lost the COX genes, with the exception of
      ctaB and ctaA, which supply the heme O and A moieties for UOX. Our results
      suggest that, in AAB, COX was replaced by beta/gamma-Proteobacterial UOX via
      horizontal gene transfer, while the COX genes, except for the heme O/A synthase
      genes, were lost. 

PMID- 24862919
TI  - Does omega-3 fatty acids supplementation affect circulating leptin levels? A
      systematic review and meta-analysis on randomized controlled clinical trials.
AB  - BACKGROUND: Omega-3 fatty acids have attracted researchers for their effect on
      circulatory hormone-like peptides affecting weight control. OBJECTIVE: Our
      objective was to conduct a systematic review and meta-analysis on randomized
      controlled trials (RCTs) assessed the effects of omega-3 supplementation on serum
      leptin concentration and to find the possible sources of heterogeneity in their
      results. METHODS: We searched PubMed/Medline, Google Scholar, Ovid, SCOPUS and
      ISI web of science up to April 2014. RCTs conducted among human adults, examined
      the effect of omega-3 fatty acid supplements on serum leptin concentrations as an
      outcome variable were included. The mean difference and standard deviation (SD)
      of changes in serum leptin levels were used as effect size for the meta-analysis.
      Summary mean estimates with their corresponding SDs were derived using random
      effects model. RESULTS: Totally 14 RCTs were eligible to be included in the
      systematic review, and the meta-analysis was performed on 13 articles. Our
      analysis showed that omega-3 supplementation significantly reduces leptin levels
      (mean difference (MD) = -1.71 ng/ml 95% confidence interval (CI): -3.17 to -0.24,
      P = 0.022). Subgroup analysis based on BMI status showed that the omega-3
      supplementation reduces leptin when used for nonobese subjects (MD = -3.60 ng/ml;
      95% CI -6.23 to -0.90; P = 0.011); however, this was not true for obese
      participants (MD = -0.86 ng/ml; 95% CI: -2.63 to -0.90; P = 0.296). Subgroup
      analysis based on omega-3 source also showed that omega-3 from marine sources may
      significantly reduce leptin levels (MD = -1.73 ng/ml; 95% CI -3.25 to -0.2; P =
      0.026), but plant sources do not significantly affect serum leptin levels (MD = 
      1.48 ng/ml; 95% CI -6.78 to 3.23; P = 0.585). Our results were highly sensitive
      to one study. CONCLUSIONS: Omega-3 supplementation might moderately decrease
      circulatory leptin levels only among nonobese adults. RCTs with longer follow-up
      period, using higher doses for obese adults and exploring the effect in different
      genders, are needed to replicate our results.

PMID- 24862921
TI  - Course of depression and anxiety symptoms during the transition to parenthood for
      female adolescents with histories of victimization.
AB  - The aim of the current study was to increase understanding of how victimization
      history impacts the longitudinal course of depression and anxiety in a sample of
      55 adolescents emerging into parenthood. Adolescents were interviewed about their
      victimization experiences during their second trimester of pregnancy, and
      interviews were subsequently classified according the Maltreatment Classification
      Scale (Barnett, Manly, & Cicchetti, 1993). Adolescents reported on their symptoms
      of depression and anxiety prenatally and 6 and 12 months postpartum. Growth curve
      modeling revealed that, on average, there was a steady linear decline in
      depression and anxiety symptoms across the transition to parenthood, with a rate
      of change of 25% and 20%, respectively, from the prenatal assessment to 12 months
      postpartum. Sexual abuse history attenuated the likelihood of a decrease in
      depressive symptoms over time. Neglect history was associated with higher
      prenatal levels of anxiety, as well as a steeper decline in anxiety symptoms over
      time. Future research is needed to determine the role of poly-victimization in
      predicting the onset and change of depression and anxiety symptoms. Findings from
      the current study have the potential to aid in the design of preventative and
      intervention efforts to reduce risks of mental health difficulties in adolescent
      parents. 

PMID- 24862922
TI  - Child maltreatment and trauma exposure among deaf and hard of hearing young
      adults.
AB  - The purpose of the present study was to examine the prevalence of child
      maltreatment and lifetime exposure to other traumatic events in a sample of deaf
      and hard of hearing (DHH; n=147) and matched hearing (H; n=317) college students.
      Participants completed measures of child maltreatment (CM), adult victimization
      and trauma exposure, and current symptoms of posttraumatic stress disorder
      (PTSD). Overall, DHH participants reported significantly more instances of CM
      compared to H participants, with 76% of DHH reporting some type of childhood
      abuse or neglect. Additionally, DHH participants reported experiencing a higher
      number of different types of CM, and also reported increased incidents of
      lifetime trauma exposure and elevated PTSD symptoms. Severity of deafness
      increased the risk of maltreatment, with deaf participants reporting more
      instances of CM than hard of hearing participants, and hard of hearing
      participants reporting more instances of CM than H participants. Among DHH
      participants, having a deaf sibling was associated with reduced risk for
      victimization, and identification with the Deaf community was associated with
      fewer current symptoms of PTSD. A regression model including measures of
      childhood physical and sexual abuse significantly predicted adult re
      victimization and accounted for 27% of the variance among DHH participants. DHH
      participants report significantly higher rates of CM, lifetime trauma, and PTSD
      symptoms compared to H participants. Severity of deafness appears to increase the
      risk of being victimized. Being part of the Deaf community and having access to
      others who are deaf appear to be important protective factors for psychological
      well-being among DHH individuals. 

PMID- 24862923
TI  - Early experience with ultrasound features after intrabeam intraoperative
      radiation for early stage breast cancer.
AB  - BACKGROUND: Intraoperative radiation therapy (IORT) is an emerging option for
      partial breast radiotherapy in select women with early stage breast cancer. We
      assessed short-term clinical and sonographic findings after breast conservation
      (BCT) and IORT. METHODS: An IRB-approved, single institution retrospective chart
      review was conducted of patients (pts) treated with BCT/IORT from 1/2011 to
      6/2012. Follow-up clinical breast exams and ultrasounds (US) obtained 6 and 12
      months after BCT/IORT were retrospectively reviewed by a single breast
      radiologist (JD) for sonographic findings. P values were calculated using
      McNemar's test, Wilcoxon Rank Sum Test, and Chi-square. RESULTS: Seventy-one pts
      underwent BCT/IORT and 38 pts had an US. All 38 pts had a seroma, 10/38 (26%) pts
      were symptomatic. Eighteen pts had deep tissue closure (DTC) of the lumpectomy
      cavity with 5/18 (28%) DTC pts being symptomatic at follow-up versus 5/33 (15%)
      without DTC (P = 0.296). At 6 months, DTC resulted in smaller seroma cavity
      volumes compared to those without DTC (P = 0.03). CONCLUSION: Presence of a
      seroma is commonplace post BCT/IORT; symptomatic seromas are uncommon. DTC
      generated smaller seromas. Longer follow-up with serial US performed in all
      BCT/IORT pts could be considered to document natural progression/regression of
      symptoms and seromas.

PMID- 24862924
TI  - Predicting the development of brain metastases in patients with local/regional
      melanoma.
AB  - BACKGROUND: The brain is a common site of recurrence in melanoma patients. Brain
      recurrence may present as a seizure, hemorrhage, or death. We sought to determine
      predictors of brain metastases in patients with primary and regional melanoma in
      order to facilitate targeted screening. METHODS: Prospectively maintained
      databases were used to identify patients treated for local or regional melanoma
      who developed stage IV melanoma with and without brain metastasis at initial
      recurrence. One hundred twenty patients were identified with brain relapse and
      compared to 487 patients without brain recurrence. RESULTS: On univariate
      analysis, patients with brain metastases were younger (55 vs. 59yrs, P = 0.04)
      but did not differ in primary site (head and neck 23% vs. 21%, P = 0.20). Brain
      metastasis patients had thinner primaries (mean 3.4 vs. 4.5 mm, P = 0.01). There
      were no other pathologic differences including ulceration (55% vs. 53%, P =
      0.75), mitoses (7 vs.7.5, P = 0.61) or histologic subtype. Younger age and
      decreased Breslow thickness were independently associated with brain metastases
      at stage IV recurrence (OR = 1.10 P = 0.01 and OR = 1.02 P = 0.02, respectively).
      CONCLUSIONS: Our analysis, the largest to date, demonstrates that thinner Breslow
      depth and younger age were associated with brain recurrence at first presentation
      with Stage IV disease.

PMID- 24862925
TI  - Clinical impact of biopsy method on the quality of surgical management in
      melanoma.
AB  - BACKGROUND AND OBJECTIVES: Though guidelines recommend excisional biopsy for
      diagnosing melanoma, partial biopsy techniques are commonly performed, risking
      underestimation of Breslow depth and altering surgical management. Biopsy choice
      patterns by specialty and subsequent impact on surgical management was examined.
      METHODS: Retrospective review of the University of Vermont Cancer Registry. All
      patients with a single, primary cutaneous melanoma from 1/02 to 6/12 analyzed.
      RESULTS: Among 853 lesions analyzed, 606 had Breslow depth <1 mm. Dermatologists
      perform 62.6% of biopsies, favoring shave biopsies; surgeons favor excisional
      biopsies (48%), and primary care doctors favor punch biopsies (44.8%), (P <
      0.001). Final Breslow depth was upstaged in 107 (12.5%); however, only 23 of 488
      partial biopsies (4.7%) displayed a discrepancy great enough to change surgical
      recommendations (P < 0.001). There was no statistically significant relationship
      with presence of ulceration, regression, high Clark level, or high mitotic index.
      CONCLUSIONS: Partial biopsy techniques are commonly performed in diagnosing
      melanoma; especially among dermatologists, who perform the majority of biopsies.
      Though partial biopsies were less accurate in determining Breslow thickness; they
      rarely alter recommendations for surgical management. Predictive features could
      not be determined to identify the few cases where a Breslow discrepancy was
      clinically relevant.

PMID- 24862926
TI  - Excellent local control with preoperative radiation therapy, surgical resection,
      and intra-operative electron radiation therapy for retroperitoneal sarcoma.
AB  - PURPOSE: To examine the value of surgical resection combined with preoperative
      external beam radiation therapy and intraoperative radiation therapy (Surg-RT)
      for retroperitoneal sarcoma (RPS). METHODS: Review of 63 consecutive patients
      with RPS from 1996 to 2011. RESULTS: Thirty-seven patients (59%) underwent Surg
      RT and 26 (41%) had surgery alone. 51% of tumors were high grade and 36% of
      patients had locally recurrent disease. Final margin status was: R0 73%, R1 16%,
      R2 6%, and unknown 5%. Of those with R0 resections, 67% received Surg-RT. Median
      follow-up was 45 months. The 5-year local control rate was 89% for Surg-RT
      patients and 46% for surgery alone patients (P = 0.03). On multivariate analysis,
      Surg-RT was the only variable associated with a lower risk of LR (HR 0.19; CI
      0.05-0.69, P = 0.003). The actuarial 5-year OS was 60% for patients receiving
      either Surg-RT or surgery alone. CONCLUSIONS: The combination of pre-operative
      radiation, surgical resection, and intraoperative radiation produces excellent
      local disease control for RPS. Combination therapy was associated with improved
      local control but not with overall survival.

PMID- 24862927
TI  - Fragmented pattern of tumor regression and lateral intramural spread may
      influence margin appropriateness after TEM for rectal cancer following
      neoadjuvant CRT.
AB  - BACKGROUND: The main tenets of local excision of rectal cancer following
      neoadjuvant chemoradiation (CRT) are that the mucosal scar represents the main
      focus of residual disease and a solid conglomerate around this rather than being
      scattered (fragmented) through the bowel wall. METHODS: Retrospective review of a
      prospective cohort of patients with residual rectal ycT1-2N0 adenocarcinoma with
      small residual tumors (<=3 cm) following CRT who underwent transanal endoscopic
      microsurgery (TEM) with 1-cm margins around the residual mucosal abnormality was
      performed. Distribution and morphology (solid vs. fragmented) of tumor spread
      were studied and correlated to postoperative oncological outcomes. RESULTS:
      Thirty patients were included. Twenty percent (n = 6) were ypT1, 60% (n = 18)
      were ypT2, and 20% (n = 6) were ypT3 tumors. Fragmentation was present in 37%.
      The mean distance between foci of residual scattered tumor was 3.6 +/- 2.0 mm.
      Lateral spread under normal mucosa was present in 19 specimens (53%; mean
      extension 4.8 +/- 2.4 mm). With a median follow up of 32 months, none of these
      findings impacted upon development of recurrence. CONCLUSIONS: Both occult
      lateral spread and fragmented tumor patterns are common findings after CRT.
      Despite the potential of occult spread to mislead surgeon choice of resection
      margin, its presence did not influence oncological outcome in this series.

PMID- 24862928
TI  - The use of assemblage models to describe trace element partitioning, speciation,
      and fate: a review.
AB  - The fate of trace elements in soils, sediments, and surface waters is largely
      determined by their binding to reactive components, of which organic matter,
      metal oxides, and clays are considered most important. Assemblage models,
      combining separate mechanistic complexation models for each of the reactive
      components, can be used to predict the solid-solution partitioning and speciation
      of trace elements in natural environments. In the present review, the authors
      provide a short overview of advanced ion-binding models for organic matter and
      oxides and of their application to artificial and natural assemblages. Modeling
      of artificial assemblages of mineral components and organic matter indicates that
      the interactions between organic and mineral components are important for trace
      element binding, particularly for oxyanions. The modeling of solid-solution
      partitioning in natural systems is generally adequate for metal cations but less
      so for oxyanions, probably because of the neglect of organic matter-oxide
      interactions in most assemblage models. The characterization of natural
      assemblages in terms of their components (active organic matter, reactive oxide
      surface) is key to successful model applications. Improved methods for
      characterization of reactive components in situ will enhance the applicability of
      assemblage models. Collection of compositional data for soil and water
      archetypes, or the development of relationships to estimate compositions from
      geospatially available data, will further facilitate assemblage model use for
      predictive purposes.

PMID- 24862929
TI  - [Guidelines of Sociedade Brasileira de Cardiologia for Unstable Angina and Non-ST
      Segment Elevation Myocardial Infarction (II Edition, 2007) 2013-2014 Update].

PMID- 24862930
TI  - Characterization of volatile aroma compounds in different brewing barley
      cultivars.
AB  - BACKGROUND: Beer is a popular alcoholic malt beverage resulting from fermentation
      of the aqueous extract of malted barley with hops. The aroma of brewing barley
      impacts the flavor of beer indirectly, because some flavor compounds or their
      precursors in beer come from the barley. The objectives of this research were to
      study volatile profiles and to characterize odor-active compounds of brewing
      barley in order to determine the variability of the aroma composition among
      different brewing barley cultivars. RESULTS: Forty-one volatiles comprising
      aldehydes, ketones, alcohols, organic acids, aromatic compounds and furans were
      identified using solid phase microextraction combined with gas
      chromatography/mass spectrometry, among which aldehydes, alcohols and ketones
      were quantitatively in greatest abundance. Quantitative measurements performed by
      means of solvent extraction and calculation of odor activity values revealed that
      acetaldehyde, 2-methylpropanal, 3-methylbutanal, 2-methylbutanal, hexanal,
      heptanal, octanal, nonanal, 3-methyl-1-butanol, cyclopentanol, 2,3-butanedione,
      2,3-pentanedione, 2-heptanone, acetic acid, ethyl acetate, 2-pentylfuran and
      benzeneacetaldehyde, whose concentrations exceeded their odor thresholds, could
      be considered as odor-active compounds of brewing barley. CONCLUSION: Principal
      component analysis was employed to evaluate the differences among cultivars. The
      results demonstrated that the volatile profile based on the concentrations of
      aroma compounds enabled good differentiation of most barley cultivars.

PMID- 24862931
TI  - The analysis of VH and VL genes repertoires of Fab library built from peripheral
      B cells of human rabies virus vaccinated donors.
AB  - A human combinatorial Fab antibody library was generated from immune repertoire
      based on peripheral B cells of ten rabies virus vaccinated donors. The analysis
      of random Fab fragments from the unselected library presented some bias of V gene
      usage towards IGHV-genes and IGLV-gen families. The screening of the Fab library
      on rabies virus allowed specific human Fab antibody fragments characterized for
      their gene encoding sequences, binding and specificities to RV. Genetic analysis
      of selected Fabs indicated that the IGHV and IGLV differ from the germ-line
      sequence. At the level of nucleotide sequences, the IGHV and IGLV domains were
      found to share 74-92% and 90-96% homology with sequences encoded by the
      corresponding human germ-line genes respectively. IGHV domains are characterized
      most frequently by IGHV3 genes, and large proportions of the anti-RV heavy chain
      IGHV domains are obtained following a VDJ recombination process that uses IGHD3,
      IGHD2, IGHD1 and IGHD6 genes. IGHJ3 and IGHJ4 genes are predominantly used in RV
      Fab. The IGLV domains are dominated by IGKV1, IGLV1 and IGLV3 genes. Numerous
      somatic hypermutations in the RV-specific IGHV are detected, but only limited
      amino acid replacement in most of the RV-specific IGLV particularly in those
      encoded by J proximal IGLV or IGKV genes are found. Furthermore, IGHV3-IGKV1,
      IGHV3-IGVL1, and IGHV3-IGLV3 germ-line family pairings are preferentially
      enriched after the screening on rabies virus. 

PMID- 24862932
TI  - ILT3.Fc inhibits the production of exosomes containing inflammatory microRNA in
      supernatants of alloactivated T cells.
AB  - Immune activation needs to be tightly regulated to control immune-mediated tissue
      damage. Inhibitory pathways serve to terminate an immune response and resolve
      inflammation. Persistent exposure to antigens can drive development of adaptive
      regulatory cells. Similarly exposure of activated T cells to the recombinant ILT3
      Fc molecule during priming triggers the differentiation of CD8 T suppressor cells
      and the induction of CD4 T helper anergy. Ts express high levels of
      immunoregulatory signature genes together with low levels of microRNA which
      control their function. Analysis of microRNA contained by exosomes from cultures
      in which T cells were alloactivated in the presence or absence of ILT3.Fc,
      demonstrated that this agent inhibits the release of inflammatory microRNA. The
      source of such inflammatory microRNA was found to reside in alloactivated CD4 T
      cells, since exosomes from MLC primed CD4 T cells were shown to diminish the
      suppressive activity of ILT3-Fc-induced CD8(+) Ts at high effector to suppressor
      T cell ratios. This indicates that inflammatory exosomes can swing the balance
      between effector and regulatory T cells in favor of immunity. These data suggest
      that isolation and characterization of micro-RNA containing exosomes in patients'
      circulation may be of use for treatment, prevention and monitoring of immune
      activation. 

PMID- 24862933
TI  - Association of an insertion/deletion polymorphism in IL1A 3'-UTR with risk for
      cervical carcinoma in Chinese Han Women.
AB  - Emerging evidence has demonstrated that polymorphisms of interleukin-1 (IL-1) may
      be involved in human tumorigenesis by regulating the production of this cytokine.
      Previous studies have investigated the association between two genetic variants
      (rs3783553 and rs17561) of IL1A and many diseases. The present study was
      conducted to evaluate whether these two variants are associated with cervical
      carcinoma (CC). These two polymorphisms were genotyped in 319 CC patients and 424
      healthy controls by polymerase chain reaction polyacrylamide gel electrophoresis
      (PCR-PAGE) and polymerase chain reaction-restriction fragment length polymorphism
      (PCR-RFLP). Significantly reduced CC risk was observed to be associated with the
      insertion allele of rs3783553 (P=0.014, OR=0.71, 95% CI=0.57-0.88).
      Stratification analysis based on different certain clinical features showed that
      patients with the heterozygous genotype were associated with a reduced
      predisposition advancing to clinical stage II-III or developing non-squamous cell
      carcinoma. Furthermore, patients with the insertion homozygous genotype were also
      associated with a reduced risk to have a poor tumor differentiation. No
      significant association was observed between rs17561 and CC. The present study
      provided evidence that the rs3783553 in IL1A 3'-UTR is inversely associated with
      CC risk, suggesting an important role IL-1alpha may play in cervical
      carcinogenesis. 

PMID- 24862935
TI  - Prevalence of diabetic retinopathy in young adults with type 1 diabetes since
      childhood: the Oulu cohort study of diabetic retinopathy.
AB  - PURPOSE: To evaluate the prevalence and stage of diabetic retinopathy (DR) in a
      population-based cohort of young Finnish adults who have had type 1 diabetes
      (T1D) since childhood. MATERIAL AND METHODS: The cohort includes all 5- to 16
      year-old patients with T1D who lived in the Northern Ostrobothnia Hospital
      District of Finland, in 1989 (n = 216). DR was evaluated from fundus photographs
      taken in 1989-1990 and again in 2007. The patients were 7 +/- 4 years age (range
      0-15 years) at the time of diagnosis of T1D, and the average duration of diabetes
      at the re-evaluation was 23 +/- 4 years (range 17-32 years). RESULTS: The
      prevalence of DR was analysed in 172 patients (80% of the original cohort) at 22
      35 years. Proliferative DR (PDR) was observed in 35% (60/172) and non
      proliferative DR in 59% (101/172), with no signs of DR being present in the
      remaining 6% (11/172) of the subjects. The prevalence of DR did not differ by
      gender (p = 0.356). CONCLUSIONS: After the 18-year follow-up, a high prevalence
      of DR and PDR (94% and 35%, respectively) was found in patients who have had T1D
      since childhood, with no difference between the genders.

PMID- 24862934
TI  - Cryptosporidium parvum induces SIRT1 expression in host epithelial cells through
      downregulating let-7i.
AB  - Epithelial cells along human gastrointestinal mucosal surface express pathogen
      recognizing receptors and actively participate in the regulation of inflammatory
      reactions in response to microbial infection. The NAD-dependent deacetylase
      sirtuin-1 (SIRT1), one member of the sirtuin family of proteins and an NAD
      dependent deacetylase has been implicated in the regulation of multiple cellular
      processes, including inflammation, longevity, and metabolism. In this study, we
      demonstrated that infection of cultured human biliary epithelial cells (H69
      cholangiocytes) with a parasitic protozoan, Cryptosporidium parvum, induced SIRT1
      expression at the protein level without a change in SIRT1 mRNA content. Using
      real-time PCR and Northern blot analyses, we found that C. parvum infection
      decreased the expression of let-7i in infected H69 cells. Down-regulation of let
      7i caused relief of miRNA-mediated translational suppression of SIRT1 and
      consequently, resulted in an increased SIRT1 protein level in infected H69 cell
      cultures. Moreover, gain- and loss-of-function studies revealed that let-7i could
      modulate NF-kappaB activation through modification of SIRT1 protein expression.
      Thus, our data suggest that let-7i regulates SIRT1 expression in human biliary
      epithelial cells in response to microbial challenge, suggesting a new role of let
      7i in the regulation of NF-kappaB-mediated epithelial innate immune response. 

PMID- 24862936
TI  - On-chip high-throughput manipulation of particles in a dielectrophoresis-active
      hydrophoretic focuser.
AB  - This paper proposes a novel concept of dielectrophoresis (DEP)-active
      hydrophoretic focusing of micro-particles and murine erythroleukemia (MEL) cells.
      The DEP-active hydrophoretic platform consists of crescent shaped grooves and
      interdigitated electrodes that generate lateral pressure gradients. These
      embedded electrodes exert a negative DEP force onto the particles by pushing them
      into a narrow space in the channel where the particle to groove interaction is
      intensive and hydrophoretic ordering occurs. Particles passing through the
      microfluidic device are directed towards the sidewalls of the channel. The
      critical limitation of DEP operating at a low flow rate and the specific
      hydrophoretic device for focusing particles of given sizes were overcome with the
      proposed microfluidic device. The focusing pattern can be modulated by varying
      the voltage. High throughput was achieved (maximum flow rate ~150 MUL min(-1))
      with good focusing performance. The non-spherical MEL cells were utilised to
      verify the effectiveness of the DEP-active hydrophoretic device.

PMID- 24862937
TI  - Describing Spirituality at the End of Life.
AB  - Spirituality is salient to persons nearing the end of life (EOL). Unfortunately,
      researchers have not been able to agree on a universal definition of spirituality
      reducing the effectiveness of spiritual research. To advance spiritual knowledge
      and build an evidence base, researchers must develop creative ways to describe
      spirituality as it cannot be explicitly defined. A literature review was
      conducted to determine the common attributes that comprise the essence of
      spirituality, thereby creating a common ground on which to base spiritual
      research. Forty original research articles (2002 to 2012) focusing on EOL and
      including spiritual definitions/descriptions were reviewed. Analysis identified
      five attributes that most commonly described the essence of spirituality,
      including meaning, beliefs, connecting, self-transcendence, and value. 

PMID- 24862938
TI  - Functional connectivity in prenatally stressed rats with and without maternal
      treatment with ladostigil, a brain-selective monoamine oxidase inhibitor.
AB  - Stress during pregnancy in humans is known to be a risk factor for
      neuropsychiatric disorders in the offspring. Prenatal stress in rats caused
      depressive-like behavior that was restored to that of controls by maternal
      treatment with ladostigil (8.5 mg/kg per day), a brain-selective monoamine
      oxidase (MAO) inhibitor that prevented increased anxiety-like behavior in
      stressed mothers. Ladostigil inhibited maternal striatal MAO-A and -B by 45-50%
      at the time the pups were weaned. Using resting state-functional connectivity
      magnetic resonance imaging on rat male offspring of control mothers, and mothers
      stressed during gestation with and without ladostigil treatment, we identified
      neuronal connections that differed between these groups. The percentage of
      significant connections within a predefined predominantly limbic network in
      control rats was 23.3 within the right and 22.0 within the left hemisphere.
      Prenatal stress disturbed hemispheric symmetry, resulting in 30.2 and 21.6%,
      significant connections in the right and left hemispheres, respectively, but this
      was fully restored in the maternal ladostigil group to 24.6% in both hemispheres.
      All connections that were modified in prenatally stressed rats and restored by
      maternal drug treatment were associated with the dopaminergic system.
      Specifically, we observed that restoration of the connections of the right
      nucleus accumbens shell with frontal areas, the cingulate, septum and motor and
      sensory cortices, and those of the right globus pallidus with the infra-limbic
      and the dentate gyrus, were most important for prevention of depressive-like
      behavior.

PMID- 24862939
TI  - Mutation profile of differentiated thyroid tumours in an Australian urban
      population.
AB  - BACKGROUND: The majority of differentiated thyroid cancers are characterised by
      one of several point mutations or gene rearrangements. Limited data are available
      on the prevalence and clinical correlations of these mutations in the Australian
      population. AIMS: The aim of the present study was to characterise the mutation
      profile of differentiated thyroid tumours in the local population. METHODS: The
      study involved 148 patients with differentiated thyroid cancer. The following
      tumours were examined: 109 papillary carcinomas (PTC), 27 follicular carcinomas
      (FC) and 12 Hurthle cell carcinomas (HCC). Polymerase chain reaction (PCR) was
      performed for BRAF and RAS mutations (RNA and DNA) as well as for RET/PTC
      rearrangements and PAX8-PPARgamma translocations (RNA). Clinicopathological
      parameters and outcome data were analysed according to BRAFV600E status in PTC
      and RAS mutation status in FC. RESULTS: BRAFV600E was identified in 74/109 (68%)
      PTC. BRAFV600E was not significantly correlated with clinicopathological features
      of aggressive disease. At a median follow up of 48 months, there was no
      significant difference between BRAFV600E and wild-type BRAF PTC with respect to
      the rates of nodal recurrence, distant metastases or disease-specific death. In
      FC, RAS mutations (five NRAS and three HRAS) were present in 8/27 (30%) tumours.
      RAS mutation was significantly associated with widely invasive histology (P =
      0.01) and distant metastases (P = 0.01) on follow up. CONCLUSION: In the present
      study, BRAF mutation was not associated with negative prognostic indicators or
      adverse outcomes in PTC. RAS mutation was positively correlated with aggressive
      features in FC suggesting potential prognostic utility, although confirmation is
      required from larger studies.

PMID- 24862940
TI  - Isolation and characterization of SSEA-4-positive subpopulation of human
      deciduous dental pulp cells.
AB  - OBJECTIVES: It is well accepted that stage-specific embryonic antigen (SSEA)-4 is
      an antigen that is useful to isolate adult stem cells analogous to embryonic stem
      cells. Therefore, in the present study, we investigated whether SSEA-4 can also
      be used as a marker to identify human deciduous dental pulp (D-DP) stem cells.
      MATERIALS AND METHODS: Intact deciduous teeth were collected from healthy
      patients who were undergoing orthodontic treatment at Okayama University
      Hospital. Immunofluorescence analysis, flow cytometric analysis, and multilineage
      differentiation assay were performed to characterize SSEA-4+ D-DP cells. RESULTS:
      The D-DP cells had the characteristics of mesenchymal stem cells (MSCs), namely
      plastic adherence, specific surface antigen expression, and multipotent
      differentiation potential. SSEA-4 expression was detected in D-DP cells in vitro
      and ex vivo samples. A flow cytometric analysis demonstrated that 21.2 % of the D
      DP cells were positive for SSEA-4. The SSEA-4+ clonal D-DP cells showed
      multilineage differentiation potential toward adipocytes, osteoblasts, and
      chondrocytes in vitro. In fact, 26.1 % (6/23) of the SSEA-4+ clonal D-DP cells
      showed adipogenic potential, 91.3 % (21/23) showed osteogenic potential, 91.3 %
      (21/23) showed chondrogenic potential, and 87.0 % (20/23) showed both osteogenic
      and chondrogenic potential. CONCLUSIONS: Thus, the majority of SSEA-4+ D-DP cells
      had the potential for multilineage differentiation. Hence, SSEA-4 appears to be a
      specific marker that can be used to identify D-DP stem cells. CLINICAL RELEVANCE:
      SSEA-4+ D-DP cells appear to be a promising source of stem cells for regenerative
      therapy.

PMID- 24862941
TI  - Neuromuscular junction disorders mimicking myopathy.
AB  - INTRODUCTION: Small-amplitude, short-duration motor unit action potentials are
      non-specific findings seen in myopathies and neuromuscular junction (NMJ)
      disorders. NMJ studies (repetitive nerve stimulation and single-fiber
      electromyography) can determine if such findings are related to NMJ abnormalities
      but are not considered routinely in atypical cases. METHODS: Medical records of
      338 patients with confirmed NMJ disorders were reviewed to identify cases with a
      clinical or electrodiagnostic impression of myopathy during initial evaluation. A
      history of muscle biopsy with findings that did not support a myopathic process
      was required for inclusion. RESULTS: Four patients met the inclusion criteria.
      NMJ studies were abnormal in all cases. One patient had elevated acetylcholine
      receptor antibodies. Three patients were antibody negative: 2 demonstrated
      immunotherapy responsiveness, and 1 had a Rapsyn mutation. CONCLUSIONS: NMJ
      disorders may mimic myopathies, and NMJ studies should be performed to clarify so
      called "myopathic" electromyographic findings to avoid unnecessary testing and
      delayed diagnosis.

PMID- 24862942
TI  - Automated interventricular septum segmentation for black-blood myocardial T2*
      measurement in thalassemia.
AB  - PURPOSE: To develop and validate an automated segmentation method that extracts
      the interventricular septum (IS) from myocardial black-blood images for the T2*
      measurement in thalassemia patients. MATERIALS AND METHODS: A total of 144
      thalassemia major patients (age range, 11-51 years; 73 males) were scanned with a
      black-blood multi-echo gradient-echo sequence using a 1.5 Tesla Siemens Sonata
      system (flip angle 20 degrees , sampling bandwidth 810 Hz/pixel, voxel size 1.56
      * 1.56 * 10 mm(3) and variable fields of view (20-30) * 40 cm(2) depending on
      patient size). The improved Chan-Vese model with an automated initialization by
      the circular Hough transformation was implemented to segment the endocardial and
      epicardial margins of the left ventricle (LV). Consequently, the IS was extracted
      by analyzing the anatomical relation between the LV and the blood pool of the
      right ventricle, identified by intensity thresholding. The proposed automated IS
      segmentation (AISS) method was compared with the conventional manual method by
      using the Bland-Altman analysis and the coefficient of variation (CoV). RESULTS:
      The T2* measurements using the AISS method were in good agreement with those
      manually measured by experienced observers with a mean difference of 1.71% and a
      CoV of 4.15% (P < 0.001). CONCLUSION: Black-blood myocardial T2* measurement can
      be fully automated with the proposed AISS method.

PMID- 24862944
TI  - SPARKLE (Subtypes of Ischaemic Stroke Classification System), incorporating
      measurement of carotid plaque burden: a new validated tool for the classification
      of ischemic stroke subtypes.
AB  - BACKGROUND: Previous classification systems of acute ischemic stroke (Causative
      Classification System, CCS, of acute ischemic stroke, Trial of Org 10172 in Acute
      Stroke Treatment, TOAST) established the diagnosis of large artery disease (LAD)
      based on the presence or absence of carotid stenosis. However, carotid plaque
      burden is a stronger predictor of cardiovascular risk than stenosis. Our
      objective was to update definitions of ischemic stroke subtypes to improve the
      detection of LAD and to assess the validity and reliability of a new
      classification system: SPARKLE (Subtypes of Ischaemic Stroke Classification
      System). METHODS: In a retrospective review of clinical research data, we
      compared three stroke subtype classifications: CCS, TOAST and SPARKLE. We
      analyzed a random sample of 275 patients presenting with minor stroke or
      transient ischemic attack (TIA) in an Urgent TIA Clinic in London, Ont., Canada,
      between 2002 and 2012. RESULTS: There was substantial overall agreement between
      SPARKLE and CCS (kappa = 0.75), with significant differences in the rate of
      detection of LAD, cardioembolic and undetermined causes of stroke or TIA. The
      inter-rater reliability of SPARKLE was substantial (kappa = 0.76) and the intra
      rater reliability was excellent (kappa = 0.91). CONCLUSION: SPARKLE is a valid
      and reliable classification system, providing advantages compared to CCS and
      TOAST. The incorporation of plaque burden into the classification of LAD
      increases the proportion of cases attributable to LAD and reduces the proportion
      classified as being of 'undetermined' etiology.

PMID- 24862943
TI  - A seascape genetic analysis reveals strong biogeographical structuring driven by
      contrasting processes in the polyploid saltmarsh species Puccinellia maritima and
      Triglochin maritima.
AB  - Little is known about the processes shaping population structure in saltmarshes.
      It is expected that the sea should act as a powerful agent of dispersal. Yet, in
      contrast, import of external propagules into a saltmarsh is thought to be small.
      To determine the level of connectivity between saltmarsh ecosystems at a macro
      geographical scale, we characterized and compared the population structure of two
      polyploid saltmarsh species, Puccinellia maritima and Triglochin maritima based
      on a seascape genetics approach. A discriminant analysis of principal components
      highlighted a genetic structure for both species arranged according to a regional
      pattern. Subsequent analysis based on isolation-by-distance and isolation-by
      resistance frameworks indicated a strong role of coastal sediment transport
      processes in delimiting regional structure in P. maritima, while additional
      overland propagule dispersal was indicated for T. maritima. The identification
      and comparison of regional genetic structure and likely determining factors
      presented here allows us to understand the biogeographical units along the UK
      coast, between which barriers to connectivity occur not only at the species level
      but at the ecosystem scale. This information is valuable in plant conservation
      and community ecology and in the management and restoration of saltmarsh
      ecosystems.

PMID- 24862945
TI  - Use of dihydroergotamine (DHE) should be restricted to no more than twice a week.

PMID- 24862946
TI  - Nuclear-spin-induced cotton-mouton effect in a strong external magnetic field.
AB  - Novel, high-sensitivity and high-resolution spectroscopic methods can provide
      site-specific nuclear information by exploiting nuclear magneto-optic properties.
      We present a first-principles electronic structure formulation of the recently
      proposed nuclear-spin-induced Cotton-Mouton effect in a strong external magnetic
      field (NSCM-B). In NSCM-B, ellipticity is induced in a linearly polarized light
      beam, which can be attributed to both the dependence of the symmetric dynamic
      polarizability on the external magnetic field and the nuclear magnetic moment, as
      well as the temperature-dependent partial alignment of the molecules due to the
      magnetic fields. Quantum-chemical calculations of NSCM-B were conducted for a
      series of molecular liquids. The overall order of magnitude of the induced
      ellipticities is predicted to be 10(-11) -10(-6) rad T(-1)  M(-1)  cm(-1) for
      fully spin-polarized nuclei. In particular, liquid-state heavy-atom systems
      should be promising for experiments in the Voigt setup. 

PMID- 24862947
TI  - Public advertising by cancer centers: are more data needed?

PMID- 24862948
TI  - Comparative analysis of Gram's stain, PNA-FISH and Sepsityper with MALDI-TOF MS
      for the identification of yeast direct from positive blood cultures.
AB  - Fungaemia diagnosis could be improved by reducing the time to identification of
      yeast from blood cultures. This study aimed to evaluate three rapid methods for
      the identification of yeast direct from blood cultures; Gram's stain analysis,
      the AdvanDX Peptide Nucleic Acid in Situ Hybridisation Yeast Traffic Light system
      (PNA-FISH YTL) and Bruker Sepsityper alongside matrix-assisted laser desorption
      ionisation time of flight mass spectrometry (MALDI-TOF MS). Fifty blood cultures
      spiked with a known single yeast strain were analysed by blinded operators
      experienced in each method. Identifications were compared with MALDI-TOF MS
      CHROMagar Candida culture and ITS rRNA sequence-based identifications. On first
      attempt, success rates of 96% (48/50) and 76% (36/50) were achieved using PNA
      FISH YTL and Gram's stain respectively. MALDI-TOF MS demonstrated a success rate
      of 56% (28/50) when applying manufacturer's species log score thresholds and 76%
      (38/50) using in-house parameters, including lowering the species log score
      threshold to >1.5. In conclusion, PNA-FISH YTL demonstrated a high success rate
      successfully identifying yeast commonly encountered in fungaemia. Sepsityper(TM)
      with MALDI-TOF MS was accurate but increased sensitivity is required. Due to the
      misidentification of commonly encountered yeast Gram's stain analysis
      demonstrated limited utility in this setting. 

PMID- 24862949
TI  - Metabolic syndrome in overweight and obese adolescents: a comparison of two
      different diagnostic criteria.
AB  - BACKGROUND: Due to the lack of consensus on its definition, the metabolic
      syndrome (MS) in children and adolescents is not formally recognized. However,
      several researchers have changed the adult criteria for pediatric standards in
      order to assess the prevalence. OBJECTIVE: The aim of this study was to evaluate
      the frequency of MS and its components according to two of the currently used
      definitions in overweight and obese adolescents. METHODS: A cross-sectional study
      with 232 adolescents with excess weight from a public school of the city of Rio
      de Janeiro. Anthropometric, blood pressure, and biochemical variables were
      assessed. MS was defined using two different diagnostic criteria: the National
      Cholesterol Education Program Adult Treatment Panel III (NCEP-ATPIII) and
      International Diabetes Federation (IDF). RESULTS: MS was diagnosed in 40.4 and
      24.6% of obese adolescents and 9.4 and 1.9% of overweight adolescents according
      to the NCEP-ATPIII and IDF criteria, respectively. The degree of agreement,
      assessed by the kappa index, from the definitions adopted in this study was 0.48.
      CONCLUSION: The results show a significant difference between the two diagnostic
      criteria. A higher frequency was found when the NCEP-ATPIII was used, which is of
      concern given the association of MS with diabetes and cardiovascular disease.

PMID- 24862950
TI  - De novo inference of protein function from coarse-grained dynamics.
AB  - Inference of molecular function of proteins is the fundamental task in the quest
      for understanding cellular processes. The task is getting increasingly difficult
      with thousands of new proteins discovered each day. The difficulty arises
      primarily due to lack of high-throughput experimental technique for assessing
      protein molecular function, a lacunae that computational approaches are trying
      hard to fill. The latter too faces a major bottleneck in absence of clear
      evidence based on evolutionary information. Here we propose a de novo approach to
      annotate protein molecular function through structural dynamics match for a pair
      of segments from two dissimilar proteins, which may share even <10% sequence
      identity. To screen these matches, corresponding 1 us coarse-grained (CG)
      molecular dynamics trajectories were used to compute normalized root-mean-square
      fluctuation graphs and select mobile segments, which were, thereafter, matched
      for all pairs using unweighted three-dimensional autocorrelation vectors. Our in
      house custom-built forcefield (FF), extensively validated against dynamics
      information obtained from experimental nuclear magnetic resonance data, was
      specifically used to generate the CG dynamics trajectories. The test for
      correspondence of dynamics-signature of protein segments and function revealed
      87% true positive rate and 93.5% true negative rate, on a dataset of 60
      experimentally validated proteins, including moonlighting proteins and those with
      novel functional motifs. A random test against 315 unique fold/function proteins
      for a negative test gave >99% true recall. A blind prediction on a novel protein
      appears consistent with additional evidences retrieved therein. This is the first
      proof-of-principle of generalized use of structural dynamics for inferring
      protein molecular function leveraging our custom-made CG FF, useful to all.

PMID- 24862951
TI  - Novel linear ion trap mass analyzer built with triangular electrodes.
AB  - A novel linear ion trap mass analyzer built with four triangular electrodes, the
      triangular-electrode linear ion trap (TeLIT), has been built and its performance
      has been characterized. The TeLIT has all the properties of a conventional LIT
      mass analyzer, performing ion trapping, mass analysis, and tandem mass
      spectrometry functions. The TeLIT was constructed with four identical triangular
      cross-section shaped electrodes and two planar electrodes. Unlike commercial
      LITs, which have very well-defined hyperbolic shaped electrodes, the TeLIT
      electrodes have a much simpler geometric structure and larger mechanical
      tolerances. The electric field distribution inside the IT region was simulated
      and there are more quadrupole field components and less higher order fields
      compared with those in other simplified ITs, such as cylindrical ion trap and
      rectilinear ion trap; hence, the instrument would potentially offer a relatively
      high mass resolution. In routine measurement, mass analysis with a resolving
      power of over 1500 at m/z = 609 Th was obtained. The TeLIT was shown to perform
      basic mass spectrometer functions such as mass-selected isolation, mass-selected
      ejection and collision-induced dissociation (CID) of ions comparable to other
      available LITs. Moreover, given the small size of the TeLIT and its simple
      structure and good analytical performance, further miniaturization and use as a
      portable mass spectrometer are envisaged. 

PMID- 24862952
TI  - Pilot and full scale applications of sulfur-based autotrophic denitrification
      process for nitrate removal from activated sludge process effluent.
AB  - Sulfur-based autotrophic denitrification of nitrified activated sludge process
      effluent was studied in pilot and full scale column bioreactors. Three identical
      pilot scale column bioreactors packed with varying sulfur/lime-stone ratios (1/1
      3/1) were setup in a local wastewater treatment plant and the performances were
      compared under varying loading conditions for long-term operation. Complete
      denitrification was obtained in all pilot bioreactors even at nitrate loading of
      10 mg NO3(-)-N/(L.h). When the temperature decreased to 10  degrees C during the
      winter time at loading of 18 mg NO3(-)-N/(L.h), denitrification efficiency
      decreased to 60-70% and the bioreactor with S/L ratio of 1/1 gave slightly better
      performance. A full scale sulfur-based autotrophic denitrification process with a
      S/L ratio of 1/1 was set up for the denitrification of an activated sludge
      process effluent with a flow rate of 40 m(3)/d. Almost complete denitrification
      was attained with a nitrate loading rate of 6.25 mg NO3(-)-N/(L.h).

PMID- 24862953
TI  - A proposed abiotic reaction scheme for hydroxylamine and monochloramine under
      chloramination relevant drinking water conditions.
AB  - Drinking water monochloramine (NH2Cl) use may promote ammonia-oxidizing bacteria
      (AOB). AOB use (i) ammonia monooxygenase for biological ammonia (NH3) oxidation
      to hydroxylamine (NH2OH) and (ii) hydroxylamine oxidoreductase for NH2OH
      oxidation to nitrite. NH2Cl and NH2OH may react, providing AOB potential benefits
      and detriments. The NH2Cl/NH2OH reaction would benefit AOB by removing the
      disinfectant (NH2Cl) and releasing their growth substrate (NH3), but the
      NH2Cl/NH2OH reaction would also provide a possible additional inactivation
      mechanism besides direct NH2Cl reaction with cells. Because biological NH2OH
      oxidation supplies the electrons required for biological NH3 oxidation, the
      NH2Cl/NH2OH reaction provides a direct mechanism for NH2Cl to inhibit NH3
      oxidation, starving the cell of reductant by preventing biological NH2OH
      oxidation. To investigate possible NH2Cl/NH2OH reaction implications on AOB, an
      understanding of the underlying abiotic reaction is first required. The present
      study conducted a detailed literature review and proposed an abiotic NH2Cl/NH2OH
      reaction scheme (RS) for chloramination relevant drinking water conditions (MUM
      concentrations, air saturation, and pH 7-9). Next, RS literature based kinetics
      and end-products were evaluated experimentally between pHs 7.7 and 8.3,
      representing (i) the pH range for future experiments with AOB and (ii) mid-range
      pHs typically found in chloraminated drinking water. In addition, a (15)N stable
      isotope experiment was conducted to verify nitrous oxide and nitrogen gas
      production and their nitrogen source. Finally, the RS was slightly refined using
      the experimental data and an AQUASIM implemented kinetic model. A chloraminated
      drinking water relevant RS is proposed and provides the abiotic reaction
      foundation for future AOB biotic experiments. 

PMID- 24862954
TI  - Production of volatile fatty acids from wastewater screenings using a leach-bed
      reactor.
AB  - Screenings recovered from the inlet works of wastewater treatment plants were
      digested without pre-treatment or dilution using a lab-scale, leach-bed reactor.
      Variations in recirculation ratio of the leachate of 4 and 8 l/lreactor/day and
      pH values of 5 and 6 were evaluated in order to determine the optimal operating
      conditions for maximum total volatile fatty acids (VFA) production. By increasing
      the recirculation ratio of the leachate from 4 to 8 l/lreactor/day it was
      possible to increase VFA production (11%) and soluble COD (17%) and thus generate
      up to 264 g VFA/kg-dry screenings. These VFA were predominantly acetic acid with
      some propionic and butyric acid. The optimum pH for VFA production was 6.0, when
      the methanogenic phase was inhibited. Below pH 5.0, acid-producing fermentation
      was inhibited and some alcohols were produced. Ammonia release during the
      hydrolysis of screenings provided adequate alkalinity; consequently, a digestion
      process without pH adjustment could be recommended. The leach-bed reactor was
      able to achieve rapid rates of screenings degradation with the production of
      valuable end-products that will reduce the carbon footprint associated with
      current screenings disposal techniques. 

PMID- 24862955
TI  - Clarifying the regulation of NO/N2O production in Nitrosomonas europaea during
      anoxic-oxic transition via flux balance analysis of a metabolic network model.
AB  - The metabolic mechanism regulating the production of nitric and nitrous oxide
      (NO, N2O) in ammonia oxidizing bacteria (AOB) was characterized by flux balance
      analysis (FBA) of a stoichiometric metabolic network (SMN) model. The SMN model
      was created using 51 reactions and 44 metabolites of the energy metabolism in
      Nitrosomonas europaea, a widely studied AOB. FBA of model simulations provided
      estimates for reaction rates and yield ratios of intermediate metabolites,
      substrates, and products. These estimates matched well, deviating on average by
      15% from values for 17 M yield ratios reported for non-limiting oxygen and
      ammonium concentrations. A sensitivity analysis indicated that the reactions
      catalysed by cytochromes aa3 and P460 principally regulate the pathways of NO and
      N2O production (hydroxylamine oxidoreductase mediated and nitrifier
      denitrification). FBA of simulated N. europaea exposure to oxic-anoxic-oxic
      transition indicated that NO and N2O production primarily resulted from an
      intracellular imbalance between the production and consumption of electron
      equivalents during NH3 oxidation, and that NO and N2O are emitted when the sum of
      their production rates is greater than half the rate of NO oxidation by
      cytochrome P460. 

PMID- 24862957
TI  - Effects of postmortem storage time on color and mitochondria in beef.
AB  - To assess the effects of aging time (0, 15, 30, and 45 d) and temperature (0 or 5
      degrees C) on beef mitochondria and steak color, vacuum packaged longissimus
      (n=15) and cardiac muscles were assigned to 1 of 6 temperature*time combinations.
      As time increased, initial red color intensity increased whereas both
      mitochondrial oxygen consumption and color stability decreased. The decrease in
      mitochondrial oxygen consumption associated with longer aging times will increase
      initial color intensity. However, this improvement in color development will be
      negated by the decreased color stability that results from the effects of storage
      on mitochondria.

PMID- 24862956
TI  - Baseline and storm event monitoring of Bacteroidales marker concentrations and
      enteric pathogen presence in a rural Canadian watershed.
AB  - Bacteroidales 16S rRNA gene markers were evaluated for their use as a microbial
      source tracking tool in a well characterized 750 ha agricultural watershed in
      Nova Scotia, Canada. Water quality monitoring was conducted following the
      validation of host-specific and universal Bacteroidales (AllBac) markers for
      their proficiency in this particular geographic region, which provided further
      evidence that these markers are geographically stable. Increasing Escherichia
      coli concentrations were positively correlated (p < 0.01) with concentrations of
      the AllBac marker in water samples, suggesting that this universal marker is more
      suited as a positive DNA control rather than as an indicator of recent fecal
      contamination. Ruminant (BacR) and bovine (CowM2) specific marker detection was
      associated with increased runoff due to precipitation in sub-watersheds
      putatively impacted by cattle farming, demonstrating that the BacR and CowM2
      markers can be used to detect the recent introduction of fecal matter from cattle
      farming activities during rainfall events. However, the human associated marker
      (BacH) was only detected once in spite of numerous on-site residential wastewater
      treatment systems in the watershed, suggesting that this assay is not sensitive
      enough to detect this type of human sewage source. E. coli O157:H7 and Salmonella
      spp. DNA was not detected in any of the 149 watershed samples; however, 114
      (76.5%) of those samples tested positive for Campylobacter spp. No significant
      correlation (p > 0.05) was found between Campylobacter spp. presence and either
      E. coli or AllBac marker levels. Further studies should be conducted to assess
      the origins of Campylobacter spp. in these types of watersheds, and to quantify
      pathogen cell numbers to allow for a human health risk assessment. 

PMID- 24862958
TI  - Subjective and objective olfactory abnormalities in Crohn's disease.
AB  - The pathogenesis of Crohn's disease (CD) is still unknown, but the involvement of
      the olfactory system in CD appears possible. No study to date has systematically
      assessed the olfactory function in CD patients. We investigated the olfactory
      function in CD patients in active (n = 31) and inactive disease (n = 27) and in a
      control group of age- and sex-matched healthy subjects (n = 35). Subjective
      olfactory testing was applied using the Sniffin' Sticks test. For olfactory
      testing, olfactory event-related potentials (OERPs) were obtained with a 4
      channel olfactometer using phenyl ethyl alcohol (PEA) and hydrogen sulfide
      (H(2)S). Carbon dioxide (CO(2)) was employed as control stimulus, and
      chemosomatosensory event-related potentials (CSSERPs) were registered. Results of
      the Sniffin' Sticks test revealed significantly different olfactory hedonic
      judgment with increased olfactory hedonic estimates for pleasant odorants in CD
      patients in active disease compared with healthy subjects. A statistical trend
      was found toward lower olfactory thresholds in CD patients. In objective
      olfactory testing, CD patients showed lower amplitudes of OERPs and CSSERPs.
      Additionally, OERPs showed significantly shorter N1- and P2 latencies following
      stimulation of the right nostril with H(2)S in CD patients in inactive disease
      compared with controls. Our study demonstrates specific abnormalities of
      olfactory perception in CD patients.

PMID- 24862959
TI  - Semiparametric modeling of grouped current duration data with preferential
      reporting.
AB  - Current duration data arise in cross-sectional studies from questions on the
      length of time from an initiating event to the time of interview. For example, in
      the National Survey on Family Growth, women who were considered at risk for
      pregnancy were asked (i) 'Are you currently attempting pregnancy?' and (ii) 'If
      yes, how many months have you been attempting to get pregnant?' The responses to
      (ii), referred to as the current durations, are length-biased because women with
      longer durations are more likely to answer yes to question (i) and therefore be
      included in the sample. Previous methods to analyze such data include continuous
      time nonparametric and parametric approaches. In this article, we propose a
      semiparametric Cox model and a piecewise constant baseline model (used to account
      for digit preference) to analyze grouped current duration data. We discuss and
      investigate through simulation studies, the robustness properties of the proposed
      methods when digit preference is present. Lastly, we present an analysis of the
      current duration data resulting from the 2002 National Survey on Family Growth.
      Published 2014. This article is a U.S. Government work and is in the public
      domain in the USA.

PMID- 24862961
TI  - Ontogeny of non-shivering thermogenesis in Muscovy ducklings (Cairina moschata).
AB  - In precocial birds, developing the capacity for early regulatory thermogenesis
      appears as a fundamental prerequisite for survival and growth in cold
      environments. However, the exact nature of these processes has not been
      thoroughly investigated. Several bird species, such as Muscovy ducks (Cairina
      moschata), develop muscular non-shivering thermogenesis when chronically exposed
      to cold. The aim of this study was to investigate the age-dependent development
      of non-shivering thermogenesis in ducklings reared either at thermoneutrality (25
      degrees C) or in the cold (4 degrees C). Non-shivering thermogenesis was assessed
      weekly by simultaneously measuring whole body metabolic heat production and
      electromyographic activity during shivering at different temperatures ranging
      from 29 degrees C to 0 degrees C. We found that ducklings reared at
      thermoneutrality displayed a capacity for non-shivering thermogenesis during the
      first month of post-hatching life. This thermogenic mechanism increased further
      in ducklings chronically exposed to a cold environment, but it decreased over
      time when birds were kept in a thermoneutral environment. 

PMID- 24862960
TI  - National prevalence and associated risk factors of hypertension and
      prehypertension among Vietnamese adults.
AB  - BACKGROUND: Hypertension has recently been identified as the leading risk factor
      for global mortality. This study aims to present the national prevalence of
      hypertension and prehypertension and, their determinants in Vietnamese adults.
      METHODS: Nationally representative data were obtained from the National Adult
      Overweight Survey 2005. This one visit survey included 17,199 subjects aged 25-64
      years, with a mean body mass index (BMI) of 20.7 kg/m(2). RESULTS: The overall
      census-weighted JNC7 (the Seventh Report of the Joint National Committee on
      Prevention, Detection, Evaluation, and Treatment of High Blood Pressure) defined
      prevalence of hypertension was 20.7% (95% confidence interval (CI) = 19.4-22.1);
      the prevalence of prehypertension was 41.8% (95% CI = 40.4-43.1). Hypertension
      and prehypertension were more prevalent in men. Higher age, overweight, alcohol
      use (among men), and living in rural areas (among women) were independently
      associated with a higher prevalence of hypertension, whereas higher physical
      activity and education level were inversely associated. Age, BMI, and living in
      rural areas were independently associated with an increased prevalence of
      prehypertension. Among the hypertensives, 25.9% were aware of their hypertension,
      12.2% were being treated, and 2.8% had their blood pressure under control; among
      the treated hypertensives, 32.4% had their blood pressure controlled.
      CONCLUSIONS: Hypertension and prehypertension are prevalent in Vietnam, but
      awareness, treatment, and control are low. The findings suggest that lifestyle
      modifications, including the prevention of overweight, the promotion of physical
      activity particularly in urban areas, and the reduction of high alcohol
      consumption, may help to prevent hypertension in Vietnam. Furthermore, increased
      efforts regarding education, detection, and treatment could be important in
      management of hypertension and cardiovascular disease risk prevention.

PMID- 24862962
TI  - Alterations in gill structure in tropical reef fishes as a result of elevated
      temperatures.
AB  - Tropical regions are expected to be some of the most affected by rising sea
      surface temperatures (SSTs) because seasonal temperature variations are minimal.
      As temperatures rise, less oxygen dissolves in water, but metabolic requirements
      of fish and thus, the demand for effective oxygen uptake, increase. Gill
      remodelling is an acclimation strategy well documented in freshwater cyprinids
      experiencing large seasonal variations in temperature and oxygen as well as an
      amphibious killifish upon air exposure. However, no study has investigated
      whether tropical reef fishes remodel their gills to allow for increased oxygen
      demands at elevated temperatures. We tested for gill remodelling in five coral
      reef species (Acanthochromis polyacanthus, Chromis atripectoralis, Pomacentrus
      moluccensis, Dascyllus melanurus and Cheilodipterus quinquelineatus) from
      populations in northern Papua New Guinea (2 degrees  35.765' S; 150 degrees 
      46.193' E). Fishes were acclimated for 12-14 days to 29 and 31 degrees C
      (representing their seasonal range) and 33 and 34 degrees C to account for end-of
      century predicted temperatures. We measured lamellar perimeter, cross-sectional
      area, base thickness, and length for five filaments on the 2nd gill arches and
      qualitatively assessed 3rd gill arches via scanning electron microscopy (SEM).
      All species exhibited significant differences in the quantitative measurements
      made on the lamellae, but no consistent trends with temperature were observed.
      SEM only revealed alterations in gill morphology in P. moluccensis. The overall
      lack of changes in gill morphology with increasing temperature suggests that
      these near-equatorial reef fishes may fail to maintain adequate O2 uptake under
      future climate scenarios unless other adaptive mechanisms are employed.

PMID- 24862963
TI  - Cost-effectiveness of the National Health Service Abdominal Aortic Aneurysm
      Screening Programme in England.
AB  - BACKGROUND: Implementation of the National Health Service abdominal aortic
      aneurysm (AAA) screening programme (NAAASP) for men aged 65 years began in
      England in 2009. An important element of the evidence base supporting its
      introduction was the economic modelling of the long-term cost-effectiveness of
      screening, which was based mainly on 4-year follow-up data from the Multicentre
      Aneurysm Screening Study (MASS) randomized trial. Concern has been expressed
      about whether this conclusion of cost-effectiveness still holds, given the early
      performance parameters, particularly the lower prevalence of AAA observed in
      NAAASP. METHODS: The existing published model was adjusted and updated to reflect
      the current best evidence. It was recalibrated to mirror the 10-year follow-up
      data from MASS; the main cost parameters were re-estimated to reflect current
      practice; and more robust estimates of AAA growth and rupture rates from recent
      meta-analyses were incorporated, as were key parameters as observed in NAAASP
      (attendance rates, AAA prevalence and size distributions). RESULTS: The revised
      and updated model produced estimates of the long-term incremental cost
      effectiveness of L5758 (95 per cent confidence interval L4285 to L7410) per life
      year gained, or L7370 (L5467 to L9443) per quality-adjusted life-year (QALY)
      gained. CONCLUSION: Although the updated parameters, particularly the increased
      costs and lower AAA prevalence, have increased the cost per QALY, the latest
      modelling provides evidence that AAA screening as now being implemented in
      England is still highly cost-effective.

PMID- 24862964
TI  - Characterization of the immune inflammatory profile in obese asthmatic children.
AB  - Asthma and obesity are two common disorders often associated in children and
      characterized by an inflammatory status. Growing evidences support a connection
      between obesity and asthma since weight reduction can improve asthmatic symptoms.
      In this study, we have enrolled eighty children: 17 non asthmatics and non obese,
      19 obese, 28 asthmatics-obese and, 16 asthmatics non-obese, respectively. In all
      participants, respiratory functional tests and body mass index (BMI) were
      calculated. Moreover, systemic inflammation of biomarkers such as T helper (h)1
      type, Th2-type and T regulatory-type serum cytokines along with major adipokines
      was determined. Data will show that the association between asthma and obesity
      leads to a predominant Th1-type response with an increase in pro-inflammatory
      cytokines. This inflammatory profile in asthmatics-obese children is sustained by
      elevated serum levels of leptin and visfatin, while adiponectin concentration is
      rather diminished. Finally, levels of systemic inflammatory biomarkers positively
      correlate with the increase in BMI values in all population subgroups. 

PMID- 24862965
TI  - Office gel sonovaginography for the prediction of posterior deep infiltrating
      endometriosis: a multicenter prospective observational study.
AB  - OBJECTIVE: To use office gel sonovaginography (SVG) to predict posterior deep
      infiltrating endometriosis (DIE) in women undergoing laparoscopy. METHODS: This
      was a multicenter prospective observational study carried out between January
      2009 and February 2013. All women were of reproductive age, had a history of
      chronic pelvic pain and underwent office gel SVG assessment for the prediction of
      posterior compartment DIE prior to laparoscopic endometriosis surgery. Gel SVG
      findings were compared with laparoscopic findings to determine the diagnostic
      accuracy of office gel SVG for the prediction of posterior compartment DIE.
      RESULTS: In total, 189 women underwent preoperative gel SVG and laparoscopy for
      endometriosis. At laparoscopy, 57 (30%) women had posterior DIE and 43 (23%) had
      rectosigmoid/anterior rectal DIE. For the prediction of rectosigmoid/anterior
      rectal (i.e. bowel) DIE, gel SVG had an accuracy of 92%, sensitivity of 88%,
      specificity of 93%, positive predictive value (PPV) of 79%, negative predictive
      value (NPV) of 97%, positive likelihood ratio (LR+) of 12.9 and negative
      likelihood ratio (LR-) of 0.12 (P = 3.98E-25); for posterior vaginal wall and
      rectovaginal septum (RVS) DIE, respectively, the accuracy was 95% and 95%,
      sensitivity was 18% and 18%, specificity was 99% and 100%, PPV was 67% and 100%,
      NPV was 95% and 95%, LR+ was 32.4 and infinity and LR- was 0.82 and 0.82 (P =
      0.009 and P = 0.003). CONCLUSIONS: Office gel SVG appears to be an effective
      outpatient imaging technique for the prediction of bowel DIE, with a higher
      accuracy for the prediction of rectosigmoid compared with anterior rectal DIE.
      Although the sensitivity for vaginal and RVS DIE was limited, gel SVG had a high
      specificity and NPV for all forms of posterior DIE, indicating that a negative
      gel SVG examination is highly suggestive of the absence of DIE at laparoscopy.

PMID- 24862966
TI  - VSIG4 expression on macrophages facilitates lung cancer development.
AB  - Tumor-associated macrophages are a prominent component of lung cancer stroma and
      contribute to tumor progression. The protein V-set and Ig domain-containing 4
      (VSIG4), a novel B7 family-related macrophage protein that has the capacity to
      inhibit T-cell activation, has a potential role in the development of lung
      cancer. In this study, 10 human non-small-cell lung cancer specimens were
      collected and immunohistochemically analyzed for VSIG4 expression. Results showed
      massive VSIG4(+) cell infiltration throughout the samples. Immunofluorescent
      double staining showed that VSIG4 was present on CD68(+) macrophages, but absent
      from CD3(+) T cells, CD31(+) endothelial cells, and CK-18(+) epithelial cells.
      Moreover, VSIG4 was coexpressed on B7-H1(+) and B7-H3(+) cells in these tumor
      specimens. Transfection of the VSIG4 gene into 293FT cells demonstrated that the
      VSIG4 signal could inhibit cocultured CD4(+) and CD8(+) T-cell proliferation and
      cytokine (IL-2 and IFN-gamma) production in vitro. Interestingly, in a murine
      tumor model induced by Lewis lung carcinoma cell line, we found that tumors grown
      in VSIG4-deficient (VSIG4(-/-)) mice were significantly smaller than those found
      in wild-type littermates. All of these results demonstrate that macrophage
      associated VSIG4 is an activator that facilitates lung carcinoma development.
      Specific targeting of VSIG4 may prove to be a novel, efficacious strategy for the
      treatment of this carcinoma. 

PMID- 24862969
TI  - Fetuin is the key for nanon self-propagation.
AB  - "Nanobacteria", also known as nanons or calciprotein particles (CPP), are nano
      sized protein mineral complexes which have been isolated from numerous biological
      sources. Nanons possess self-replication properties and contain only serum
      proteins (e.g. Fetuin-A, Albumin). Herein, we develop a simplified in vitro model
      of nanons propagation composed of only fetuin-A as a protein. Using this model,
      we demonstrate that fetuin from nanons possesses a different, non-native
      conformation. Moreover, we show that nanons induce soluble fetuin-A precipitation
      which could serve as a template for calcification. This phenomenon explains the
      observed self-propagating properties that mimic infectious behavior. We also
      demonstrate that renal calculi are capable of inducing a conformational change in
      fetuin-A, suggesting that the propagation phenomenon of nanons may occur in vivo.

PMID- 24862967
TI  - Mouse models of mantle cell lymphoma, complex changes in gene expression and
      phenotype of engrafted MCL cells: implications for preclinical research.
AB  - Mantle cell lymphoma (MCL) is an aggressive type of B-cell non-Hodgkin lymphoma
      (NHL) associated with poor prognosis. Animal models of MCL are scarce. We
      established and characterized various in vivo models of metastatic human MCL by
      tail vein injection of either primary cells isolated from patients with MCL or
      established MCL cell lines (Jeko-1, Mino, Rec-1, Hbl-2, and Granta-519) into
      immunodeficient NOD.Cg-Prkdc(scid) Il2rg(tm1Wjl)/SzJ mice. MCL infiltration was
      assessed with immunohistochemistry (tissues) and flow cytometry (peripheral
      blood). Engraftment of primary MCL cells was observed in 7 out of 12 patient
      samples. The pattern of engraftment of primary MCL cells varied from isolated
      involvement of the spleen to multiorgan infiltration. On the other hand, tumor
      engraftment was achieved in all five MCL cell lines used and lymphoma involvement
      of murine bone marrow, spleen, liver, and brain was observed. Overall survival of
      xenografted mice ranged from 22 +/- 1 to 54 +/- 3 days depending on the cell line
      used. Subsequently, we compared the gene expression profile (GEP) and phenotype
      of the engrafted MCL cells compared with the original in vitro growing cell lines
      (controls). We demonstrated that engrafted MCL cells displayed complex changes of
      GEP, protein expression, and sensitivity to cytotoxic agents when compared with
      controls. We further demonstrated that our MCL mouse models could be used to test
      the therapeutic activity of systemic chemotherapy, monoclonal antibodies, or
      angiogenesis inhibitors. The characterization of MCL murine models is likely to
      aid in improving our knowledge in the disease biology and to assist scientists in
      the preclinical and clinical development of novel agents in relapsed/refractory
      MCL patients.

PMID- 24862970
TI  - Gonadotropin-dependent precocious puberty in an 8-year-old boy with leydig cell
      testicular tumor.
AB  - Leydig cell testicular tumors are very rare in children. They can present as
      gonadotropin-independent precocious puberty due to excess androgen secretion. We
      report the case of an 8-year-old boy with isosexual precocity whose hormonal
      investigation showed luteinizing hormone-independent testosterone hypersecretion.
      Although no palpable mass was present, scrotal ultrasound revealed a testicular
      tumor. Testis-sparing tumor resection was performed and the histopathology
      analysis showed a Leydig cell tumor. After surgery the testosterone levels
      remained high and further examination showed gonadotropin-dependent precocious
      puberty, which is believed to be likely caused by the activation of the
      hypothalamic-pituitary axis due to a long-term exposition to sex steroids. He is
      currently being treated with a long-acting gonadotropin-releasing hormone analog
      and the process of sexual precocity has until now been suppressed.

PMID- 24862968
TI  - The aldosterone receptor antagonist spironolactone prevents peritoneal
      inflammation and fibrosis.
AB  - Peritoneal fibrosis is a complication of patients with long-term continuous
      ambulatory peritoneal dialysis (CAPD). Reports have indicated that angiotensin
      (Ang) II may correlate with the development of peritoneal fibrosis. However, it
      is unknown whether aldosterone also has a role in the development of peritoneal
      inflammation and fibrosis. The aim of the present study was to clarify the role
      of aldosterone in peritoneal inflammation and fibrosis. A rat model of peritoneal
      inflammation and fibrosis was established by daily intraperitoneal injection of
      dialysates and lipopolysaccharide in a 4-day interval over a period of 7 days.
      The animals were randomly assigned to five groups as follows: control (C);
      peritoneal dialysis (PD); peritoneal dialysis-spironolactone (PD-S); peritoneal
      dialysis-cilazapril (PD-C); and peritoneal dialysis-spironolactone-cilazapril (PD
      SC). After 30 days, the TGF-beta1 concentration in dialysates from all treatment
      groups was determined by ELISA. The histopathology of the parietal peritoneum was
      examined, and the expression of MCP-1, c-Jun, fibronectin (FN) and TGF-beta1 in
      the abdominal membrane was determined by immunohistochemistry. Mineralocorticoid
      receptor (MR), 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) and
      CYP11B2 (aldosterone synthase) were analyzed by real time-PCR. Collagen
      deposition was significantly higher in PD compared with the other groups. The
      expression of MR, 11beta-HSD2 and CYP11B2 was significantly higher in PD compared
      with the other groups. Spironolactone and/or cilazapril treatment partially
      ablated the increase in monocyte chemoattractant protein (MCP)-1, p-c-Jun,
      transforming growth factor (TGF)-beta1, FN, MR, 11beta-HSD2 and CYP11B2.
      Furthermore, treatment with spironolactone and/or cilazapril also reduced the
      infiltration of CD-4- and ED-1-positive cells in rat peritoneal tissues after
      peritoneal fibrosis. Exogenous aldosterone may have a key role in the development
      of peritoneal inflammation and fibrosis. Spironolactone decreased peritoneal
      inflammation and fibrosis, which was associated with reduced secretion from
      peritoneal macrophages, inactivation of the c-Jun N-terminal kinase (JNK) pathway
      and subsequent downregulation of the expression of TGF-beta1. 

PMID- 24862972
TI  - Development of the spatial coding of touch: ability vs. automaticity.

PMID- 24862971
TI  - Nicotine concentrations in electronic cigarette refill and do-it-yourself fluids.
AB  - INTRODUCTION: We evaluated the accuracy of nicotine concentration labeling on
      electronic cigarette refill products. METHODS: The nicotine concentration of 71
      electronic cigarette refill fluid products and 1 related do-it-yourself (DIY)
      product was quantified using high-performance liquid chromatography. Quantified
      data were compared with manufacturers labeled concentrations. Duplicate refill
      fluid products purchased at different times were evaluated by visual comparison
      of fluid coloration and quantified nicotine concentration. RESULTS: Thirty-five
      of the 54 nicotine-containing fluids had quantified nicotine concentrations that
      deviated by more than +/- 10% from the manufacturer labels, with 46 of 50 being
      in excess of labeled values. Refill fluids labeled as 0 nicotine had no
      detectable nicotine. Of the 5 products that were unlabeled for nicotine
      concentration, 3 contained no detectable nicotine, whereas the remaining 2
      contained nicotine in excess of 100mg/ml and may have been intended for DIY use.
      Sixteen of the 18 duplicate bottles of refill fluid varied greatly in their
      nicotine concentrations. One of the 5 companies showed significant improvement in
      labeling accuracy among the most recently purchased products. Of the 23 total
      duplicate pairs, 15 of 23 varied in coloration from their mates. CONCLUSIONS:
      Nicotine concentration labeling on electronic cigarette refill products was often
      inaccurate but showed improvement recently in products from 1 company. To ensure
      the safety of refill fluids and DIY products, it is necessary to establish
      quality control guidelines for the manufacturing and labeling and to monitor
      products longitudinally.

PMID- 24862973
TI  - Iron decreases biological effects of ozone exposure.
AB  - CONTEXT: Ozone (O3) exposure is associated with a disruption of iron homeostasis
      and increased availability of this metal which potentially contributes to an
      oxidative stress and biological effects. OBJECTIVE: We tested the postulate that
      increased concentrations of iron in cells, an animal model and human subjects
      would significantly impact the biological effects of O3 exposure. RESULTS:
      Exposure to 0.4 ppm O3 for 5 h increased mRNA for both Superoxide Dismutase-1
      (SOD1) and Cyclooxygenase-2 (COX2) in normal human bronchial epithelial (NHBE)
      cells. Pre-treatment of NHBE cells with 200 uM ferric ammonium citrate (FAC) for
      4 h diminished changes in both SOD1 and COX2 following O3 exposure. mRNA
      transcript levels and associated protein release of the pro-inflammatory
      mediators IL-6 and IL-8 were increased by O3 exposure of NHBE cells; changes in
      these endpoints after O3 exposure were significantly decreased by FAC pre
      treatment of the cells. Exposure of CD-1 mice to 2 ppm O3 for 3 h significantly
      increased lavage indices of inflammation and airflow limitation. Pre-treatment of
      the animals with pharyngeal aspiration of FAC diminished the same endpoints.
      Finally, the mean loss of pulmonary function in 19 healthy volunteers exposed to
      0.3 ppm O3 for 2 h demonstrated significant correlations with either their pre
      exposure plasma ferritin or iron concentrations. DISCUSSION AND CONCLUSION: We
      conclude that greater availability of iron after O3 exposure does not augment
      biological effects. On the contrary, increased available iron decreases the
      biological effects of O3 exposure in cells, animals and humans.

PMID- 24862975
TI  - Route of exposure alters inflammation and lung function responses to diesel
      exhaust.
AB  - CONTEXT: Mice are commonly used in studies investigating the effects of diesel
      exhaust exposure on respiratory health. A plethora of studies in this field has
      resulted in a range of exposure protocols, from inhalation of diesel exhaust, to
      the administration (via various routes) of diesel exhaust particles in solution.
      OBJECTIVE: In this study, we compared the physiological consequences of short
      term exposure to diesel exhaust via inhalation to those due to exposure to the
      same diesel exhaust particles suspended in solution and delivered intranasally.
      MATERIALS AND METHODS: Adult BALB/c mice were exposed to diesel exhaust via
      inhalation for 2 hours per day for 8 days. A representative, simultaneous sample
      of particles was collected and a second group of mice then exposed to them
      suspended in saline. A low and a high-dose were studied, with these matched based
      on respiratory parameters. Six and twenty-four hours after the last exposure we
      measured bronchoalveolar inflammation, lung volume, lung function and the amount
      of elemental carbon in alveolar macrophages. RESULTS: Exposure via either route
      elicited pulmonary inflammation and changes in lung function. We identified
      significant differences in response between the two routes of exposure, with mice
      exposed via inhalation generally displaying more realistic dose-response
      relationships. Mice exposed via intranasal instillation responded more variably,
      with little influence of dose. CONCLUSIONS: Our results suggest that selection of
      the route of exposure is of critical importance in studies such as this. Further,
      inhalation exposure, while more methodologically difficult, resulted in responses
      more akin to those seen in humans.

PMID- 24862976
TI  - The effect of smoking on CT score, bacterial colonization and distribution of
      inflammatory cells in the upper airways of patients with chronic rhinosinusitis.
AB  - OBJECTIVE: The study was designed to determine whether smoking affects CT score,
      bacterial colonization of the upper airways and distribution of inflammatory
      cells in nasal mucosa in patients with chronic rhinosinusitis. MATERIAL AND
      METHODS: Sixty-four patients were enrolled in the prospective study. We
      characterized differences in CT score, rate of revision surgery, differences in
      bacterial colonization in the middle nasal meatus and distribution of
      inflammatory cells in nasal tissue in smoking and non-smoking patients with
      chronic rhinosinusitis with nasal polyps (CRSwNP), chronic rhinosinusitis without
      nasal polyps (CRSsNP) and control group. RESULTS: Direct tobacco use was
      associated with significantly more severe form of the disease according to the
      preoperative CT investigation of paranasal sinuses using Lund-Mackay scoring
      system in both CRSwNP (p = 0.035) and CRSsNP (p = 0.023) groups. More intense
      colonization of upper-respiratory tract by the pathogenic bacteria in smokers
      compared to non-smokers was found. Non-pathogenic bacterial flora was more often
      present in non-smokers compared to smokers. Plasma cells and lymphocytes were the
      most numerous cells in nasal tissue in all three groups. In smokers with presence
      of pathogenic bacteria in middle nasal meatus there was stronger neutrophil (p =
      0.002) and macrophage infiltration (p = 0.044) in CRSsNP group. CONCLUSION:
      Tobacco smoke exposure is related to higher Lund-Mackay score, increased
      colonization by pathogenic bacteria and lower incidence of commensals in middle
      nasal meatus, but does not influence cell distribution in nasal mucosa in
      patients with chronic rhinosinusitis.

PMID- 24862974
TI  - Development and characterization of an exposure platform suitable for physico
      chemical, morphological and toxicological characterization of printer-emitted
      particles (PEPs).
AB  - An association between laser printer use and emissions of particulate matter
      (PM), ozone and volatile organic compounds has been reported in recent studies.
      However, the detailed physico-chemical, morphological and toxicological
      characterization of these printer-emitted particles (PEPs) and possible
      incorporation of engineered nanomaterials into toner formulations remain largely
      unknown. In this study, a printer exposure generation system suitable for the
      physico-chemical, morphological, and toxicological characterization of PEPs was
      developed and used to assess the properties of PEPs from the use of commercially
      available laser printers. The system consists of a glovebox type environmental
      chamber for uninterrupted printer operation, real-time and time-integrated
      particle sampling instrumentation for the size fractionation and sampling of PEPs
      and an exposure chamber for inhalation toxicological studies. Eleven commonly
      used laser printers were evaluated and ranked based on their PM emission
      profiles. Results show PM peak emissions are brand independent and varied between
      3000 to 1 300 000 particles/cm3, with modal diameters ranging from 49 to 208 nm,
      with the majority of PEPs in the nanoscale (<100 nm) size. Furthermore, it was
      shown that PEPs can be affected by certain operational parameters and printing
      conditions. The release of nanoscale particles from a nano-enabled product
      (printer toner) raises questions about health implications to users. The
      presented PEGS platform will help in assessing the toxicological profile of PEPs
      and the link to the physico-chemical and morphological properties of emitted PM
      and toner formulations.

PMID- 24862978
TI  - p-i-n Heterojunction solar cells with a colloidal quantum-dot absorber layer.
AB  - A quantum-dot (QD) p-i-n heterojunction solar cell with an increased depletion
      region is demonstrated by depleting the QD layer from both the front and back
      junctions. Due to a combination of improved charged extraction and increased
      light absorption, a 120% increase in the short-circuit current is achieved
      compared with that of conventional ZnO/QD devices. 

PMID- 24862979
TI  - Bone microarchitecture and strength of the radius and tibia in a reference
      population of young adults: an HR-pQCT study.
AB  - Within a normative youth cohort (16-29 years) bone parameters for males and
      females remained stable at the radius. At the tibia, a peak was observed for
      females at 16-19 years, with bone density and strength decreasing by 29 years.
      PURPOSE: To determine if bone microstructural and strength parameters identified
      by high-resolution peripheral quantitative computed tomography (HR-pQCT) and
      finite element analysis (FEA) at the distal radius and tibia, peak within the age
      range of this youth cohort, and whether the timing of the peaks differ based on
      sex or skeletal site. METHODS: We recruited 251 participants (158 female; 16 to
      29 years), grouping them into 5-year age brackets (16-19; 20-24; 25-29 years)
      assessing microstructural and strength parameters with HR-pQCT and FEA. RESULTS:
      HR-pQCT assessment of males and females (age-matched groups) showed males had
      higher total area and BMD, trabecular BMD and trabecular number (radius only)
      cortical thickness and porosity, and failure load, but lower cortical BMD (p <
      0.05). Within sex, microstructural and strength parameters remained stable for
      males, but in females they appeared to peak at 16-19 years at the tibia. Tibia
      bone strength and trabecular BMD were highest in females 16-19 years (p < 0.05),
      and tibia cortical porosity was lowest in females 16-19 years (p < 0.001). With
      the exception of an age-related increase in cortical BMD, all other parameters
      were stable between 16 and 29 years at the radius for both males and females. We
      found no peak values for males or females at the radius. At the tibia, a peak was
      observed for females 16-19 years. CONCLUSION: These data provide a population
      based assessment of bone microstructural and strength parameters from HR-pQCT and
      FEA in a youth cohort, showing clear differences in bone quality dependent on sex
      and skeletal site.

PMID- 24862980
TI  - A nationwide register study of the characteristics, incidence and validity of
      diagnosed Tourette syndrome and other tic disorders.
AB  - AIM: The aim of this study was to describe the characteristics and incidence
      rates of diagnosed tic disorders in the Finnish Hospital Discharge Register,
      including changing incidence rates between 1991 and 2010. We also aimed to
      validate the diagnoses of Tourette's syndrome recorded in the register. METHODS:
      Children born between January 1, 1991 and December 31, 2010, who were diagnosed
      with tic disorders, were identified from the Finnish Hospital Discharge Register
      (n = 3003). We studied the validity of the Tourette's syndrome diagnoses by
      reviewing the medical charts of 88 children born since 1997 and carrying out
      telephone interviews with 55 of their guardians. RESULTS: The incidence rates of
      all diagnosed tic disorders increased during the study period. A comorbid
      diagnosis of hyperkinetic disorder diagnosis was recorded in 28.2% of the
      children with Tourette's syndrome, and the validity of the register-based
      Tourette's syndrome diagnosis was approximately 95%. CONCLUSION: This is the
      first nationwide study to demonstrate the increasing incidence of all register
      based tic disorder diagnoses. The validity of the Tourette's syndrome diagnoses
      in the Finnish Hospital Discharge Register was good, and the data provided are
      suitable for use in further register-based studies of tic disorders.

PMID- 24862977
TI  - Plasma nitrite is an indicator of acute changes in ambient air pollutant
      concentrations.
AB  - CONTEXT: Endothelial dysfunction has been suggested as a potential mechanism by
      which ambient air pollution may cause acute cardiovascular events. Recently,
      plasma nitrite has been developed as a marker of endothelial dysfunction.
      OBJECTIVES: We examined the changes in plasma nitrite concentration associated
      with increases in ambient air pollutant concentrations in the previous 7 d.
      MATERIALS AND METHODS: We linked up to three measurements of plasma nitrite
      concentrations obtained from 49 students to 24-h average concentrations of five
      criteria air pollutants [particle mass < 2.5 um in aerodynamic diameter
      (PM(2.5)), carbon monoxide (CO), sulfur dioxide (SO2), nitrogen dioxide (NO2),
      and ozone (O3)] measured at two monitoring sites closest to Rutgers University
      campus (6-15 miles) in New Jersey during the years 2006-2009. We examined the
      change in plasma nitrite associated with each interquartile-range (IQR) increase
      in pollutant concentration in the previous 24 h and six preceding 24- h periods,
      using linear mixed models. RESULTS: IQR increases in mean PM(2.5) (7.0 ug/m3) and
      CO (161.7 parts per billion) concentrations in the first 24 h before the plasma
      nitrite measurement were associated with increased plasma nitrite concentrations
      (PM(2.5): 15.5 nanomolar; 95% confidence interval (CI): 2.4, 28.5; CO: 15.6
      nanomolar; 95% CI: 2.4, 28.9). Increased plasma nitrite associated with IQR
      increases in O3 and SO2 concentrations over longer lags were observed. DISCUSSION
      AND CONCLUSION: Rapid increases in plasma nitrite following exposure to ambient
      air pollutants support the hypothesis that ambient air pollution is associated
      with inducible nitric oxide synthase-mediated systemic inflammation in humans.

PMID- 24862981
TI  - The effect of floods on sediment contamination in a microtidal coastal lagoon:
      the lagoon of Lesina, Italy.
AB  - The effects on the microtidal lagoon of Lesina of runoff and the discharge of
      water and material from agricultural activities were investigated combining
      chemical analyses of pollutants [11 metals and 16 priority polycyclic aromatic
      compounds (PAHs)], determination of organic matter and grain size, and
      performance of innovative ecotoxicological tests. For metals, enrichment factors
      >3 for arsenic, nickel, and copper (Cu) were observed in the eastern zone of the
      lagoon, which is affected by nearby urban activities with discharge of water and
      domestic waste and by agricultural input with waters rich in fertilizers. Cu was
      correlated with no other metal, and its high concentrations (<=77 ug g(-1)) may
      result from the use of Cu-based fungicides in vineyards. Total PAHs (2,230 +/-
      3,150 ng g(-1)) displayed a wide range of concentrations with hot spots near
      freshwater inputs from the part of the catchment area exploited for wheat crops.
      Pyrolitic contamination also emerged, with higher-mass PAH congeners, such as
      asphalt, bitumen or coal, usually present in higher fractions as the dominant
      components. Ecotoxicological evaluations recorded moderate to high toxicity
      levels; the innovative MOT test bioassay showed good discriminatory ability
      because it identified a lagoon area whose inputs mainly depend on agricultural
      activities and which is impacted by metals rather than PAHs. Floods during
      periods of heavy rain and the discharge of water and material from agricultural
      activities may impact vulnerable systems, such as the lagoon of Lesina, where the
      presence of hot spots with remarkably high pollution values was observed. 

PMID- 24862982
TI  - Multifocal motor neuropathy: correlation of nerve ultrasound,
      electrophysiological, and clinical findings.
AB  - We present nerve ultrasound findings in multifocal motor neuropathy (MMN) and
      examine their correlation with electrophysiology and functional disability.
      Eighty healthy controls and 12 MMN patients underwent clinical, sonographic, and
      electrophysiological evaluation a mean of 3.5 years (standard deviation [SD] +/-
      2.1) after disease onset. Nerve ultrasound revealed significantly higher cross
      sectional area (CSA) values of the median (forearm, p < 0.001), ulnar (p <
      0.001), and tibial nerve (ankle, p < 0.001) when compared with controls.
      Electroneurography documented signs of significantly lower values of the motor
      conduction velocity and compound muscle action potentials (cMAPs) in the upper
      arm nerves (median, ulnar, radial, p < 0.001). A significant correlation between
      sonographic and electrophysiological findings in the MMN group was found only
      between cMAP and CSA of the median nerve at the upper arm (r = 0.851, p < 0.001).
      Neither nerve sonography nor electrophysiology correlated with functional
      disability. MMN seems to show inhomogeneous CSA enlargement in various peripheral
      nerves, with weak correlation to electrophysiological findings. Neither nerve
      sonography nor electrophysiology correlated with functional disability.
      Multicentre, prospective studies are required to prove the applicability and
      diagnostic values of these findings. 

PMID- 24862983
TI  - Additional resources and the default mode network: Evidence of increased
      connectivity and decreased white matter integrity in amyotrophic lateral
      sclerosis.
AB  - In amyotrophic lateral sclerosis (ALS), cognition is affected. Cortical atrophy
      in frontal and temporal areas has been associated with the cognitive profile of
      patients. Additionally, reduced metabolic turnover and regional cerebral blood
      flow in frontal areas indicative of reduced neural activity have been reported
      for ALS. We hypothesize that functional connectivity in non-task associated
      functional default mode network (DMN) is associated with cognitive profile and
      white matter integrity. This study focused on specific cognitive tasks known to
      be impaired in ALS such as verbal fluency and attention, and the relationship
      with functional connectivity in the DMN and white matter integrity. Nine patients
      and 11 controls were measured with an extensive neuropsychological battery.
      Resting-state functional magnetic resonance imaging (fMRI) and diffusion tensor
      imaging (DTI) data were acquired. Results showed that ALS patients performed
      significantly worse in attention and verbal fluency task. Patients showed
      increased functional connectivity in parahippocampal and parietal areas of the
      non-task associated DMN compared to controls. The more pronounced the cognitive
      deficits, the stronger the increase in functional connectivity in those areas.
      White matter integrity was reduced in frontal areas in the patients. In
      conclusion, increased connectivity in the DMN in parahippocampal and parietal
      areas might represent recruitment of accessory brain regions to compensate for
      dysfunctional frontal networks.

PMID- 24862984
TI  - A fluorescent sensor to detect sodium dodecyl sulfate based on the glutathione
      stabilized gold nanoclusters/poly diallyldimethylammonium chloride system.
AB  - A simple method for the detection of sodium dodecyl sulfate (SDS) was developed
      based on glutathione-stabilized gold nanoclusters (GSH-AuNCs) and
      poly(diallyldimethylammonium)chloride (PDDA) enhanced fluorescent system.
      Fluorescent Au NCs were synthesized by a one-step approach employing GSH as
      reducing/protecting reagent. The electrostatic group repulsions between GSH-Au
      NCs and PDDA resulted in strong fluorescence enhancement from the GSH-Au NCs.
      Moreover, the addition of SDS was able to cause a significant fluorescence
      recovery due to the strong affinity of PDDA and SDS. Thus the SDS can be
      detected. Under optimized conditions, the linear response to detect SDS ranges
      from 0.2 to 12 ug mL(-1) with a detection limit of 0.02 ug mL(-1). 

PMID- 24862985
TI  - GATA4 immunolocalization in breast carcinoma as a potent prognostic predictor.
AB  - Transcriptional GATA factors are known lineage selector genes and regulate a
      variety of biological processes including specification and differentiation of
      tissues. In the present study, we examined expression profiles of six GATA factor
      genes in invasive ductal carcinomas (IDC) of the breast using microarray analysis
      (n = 20) and found that GATA4 expression was closely correlated with recurrence
      in patients. Because the significance of GATA4 has remained largely unknown in
      breast carcinoma, we further immunolocalized GATA4 in ductal carcinoma in situ
      (DCIS) of the breast (n = 48) and IDC (n = 163). GATA4 immunoreactivity was
      detected in the nuclei of carcinoma cells and was positive in 27% of DCIS and 31%
      of IDC cases. GATA4 status was significantly associated with nuclear grade and
      van Nuys classification in DCIS and was positively associated with distant
      metastasis, histological grade and HER2 status, but negatively correlated with
      progesterone receptor labeling index in IDC. Subsequent multivariate analysis
      demonstrated that GATA4 status was an independent prognostic factor for both
      disease-free and breast cancer-specific survival of IDC patients. All of these
      results indicate that GATA4 plays important roles in the progression of breast
      carcinoma from an early stage and that immunohistochemical GATA4 status is
      considered a potent prognostic factor in human breast cancer patients.

PMID- 24862986
TI  - HSP70, Peroxiredoxin-3 and -6 are upregulated during renal warm ischaemia in a
      donation after circulatory death model.
AB  - BACKGROUND: The use of donation after circulatory death (DCD) kidneys for
      transplantation is increasing. Subsequent delayed graft function is related to
      ischaemia/reperfusion injury (I/R), warm ischaemia (WI) being one of the main
      contributing factors. This proteomics study aimed to identify candidate
      biomarkers of WI. METHODS: Termination biopsies were obtained over 180min in 6
      pigs. Proteins were subjected to differential in-gel electrophoresis (DIGE) and
      identified using LC MS/MS. RESULTS: Thirty nine protein spots showed significant
      changes in expression (ANOVA, p<0.05). Peroxiredoxin-3 and -6 (PRX3 and PRX6)
      were expressed with a fold change (FD) of +1.8 (p=0.03 and 0.02 respectively). A
      significant upregulation of Alpha-2-HS-glycoprotein (A2HSG, FD+1.9, p=0.047) and
      heat-shock protein 70-1b (HSP70-1b, FD+2.1 p=0.002) was recorded. CONCLUSIONS:
      The expression of PRX3, PRX6 and HSP70-1b during the first 30min of WI may be
      critical in measuring cellular responses. This is the first large animal model to
      describe the novel candidate biomarker, structural protein A2HSG. A2HSG
      upregulation during WI alone in this study is encouraging and further assessment
      in a DCD auto-transplant model is warranted. BIOLOGICAL SIGNIFICANCE: Warm
      ischaemia (WI) during donation after circulatory death (DCD) organ retrieval is
      associated with higher rates of post transplant organ dysfunction. The cellular
      and molecular mechanism of this paradigm is poorly reported. The work carried out
      in this large animal study has been performed to enable better understanding of
      protein expression during DCD WI at the time of retrieval. We have identified
      differential increased expression of PRX3, PRX6 and HSP70 during the first 30min
      of WI. Observation of this behaviour has not been reported before. Application of
      these results in a reperfusion model or autograft animal study would further help
      study of the named proteins as clinical biomarkers of WI. Alpha 2-HS Glycoprotein
      (A2HSG) species were also differentially expressed during the WI period. This
      remains a novel finding. Assessment of A2HSG is also recommended for further
      study in a reperfusion context. Previous reports of A2HSG have suggested an
      association in chronic kidney disease and diabetes, but no association with WI
      has previously been noted in either small or large animals.

PMID- 24862988
TI  - The effect of dispersion interactions on the properties of LiF in condensed
      phases.
AB  - Classical molecular dynamics simulations are performed on LiF in the framework of
      the polarizable ion model. The overlap repulsion and polarization terms of the
      interaction potential are derived on a purely non-empirical, first-principles
      basis. For the dispersion, three cases are considered: a first one in which the
      dispersion parameters are set to zero and two others in which they are included,
      with different parametrizations. Various thermodynamic, structural and dynamic
      properties are calculated for the solid and liquid phases. The melting
      temperature is also obtained from direct coexistence simulations of the liquid
      and solid phases. Dispersion interactions appear to have an important effect on
      the densities of both phases and on the melting point, although the liquid
      properties are not affected when simulations are performed in the NVT ensemble at
      the experimental density. 

PMID- 24862989
TI  - Long-lasting Consequences of Early Life Stress on Brain Structure, Emotion and
      Cognition.
AB  - During the perinatal period, the brain undergoes substantial structural changes,
      synaptic rearrangements, and development of neuronal circuits which ultimately
      determine brain function and behavior. Environmental factors-such as exposure to
      adverse experiences-have major impact on brain function and structure during this
      sensitive period. These alterations can be long-lasting, and have been implicated
      in psychopathology such as cognitive decline and emotional dysfunction. Here we
      briefly review how early postnatal adversity determines structure and function of
      the hippocampus, amygdala, and prefrontal cortex (PFC) areas, which are crucial
      for proper cognitive and emotional function. 

PMID- 24862987
TI  - Whole genome identification of C. trachomatis immunodominant antigens after
      genital tract infections and effect of antibiotic treatment of pigtailed
      macaques.
AB  - The cervix and/or fallopian tubes of pigtailed macaques were experimentally
      infected with Chlamydia trachomatis. Their sera were collected at varying time
      points and screened for identification of immunodominant antigens using a whole
      genome protein microarray. The effect of doxycycline treatment on the antibody
      response generated in these macaques was also investigated. Twenty-five female
      macaques were infected with C. trachomatis serovars D or E in the cervix and/or
      fallopian tubes. Bloods were collected at baseline and at various intervals after
      challenge. Serum samples were tested for antibodies using a C. trachomatis
      serovar D protein microarray. Twenty chlamydial antigens reacted with sera from
      at least 68% (17/25) of the macaques. In addition to some well-known chlamydial
      antigens, nine different proteins, not previously recognized as immunodominant,
      including four hypothetical proteins (CT005, CT066, CT360 and CT578), were
      identified. Monkeys infected in the fallopian tubes developed a more robust
      antibody response than animals inoculated in the cervix. Treatment with
      doxycycline significantly decreased Chlamydia-specific antibody levels. In
      summary, using protein microarray serum samples from experimentally infected
      pigtailed macaques were screened for immunodominant chlamydial antigens. These
      antigens can now be tested in animal models for their ability to protect and as
      markers of disease progression. BIOLOGICAL SIGNIFICANCE: This is the first time
      that Chlamydia trachomatis immunodominant antigens have been identified in
      pigtailed macaques following a uterine cervix or a fallopian tubes infection.
      These immunodominant antigens can now be used to vaccinate non-human primates and
      determine their ability to protect against a C. trachomatis genital infection.
      Proteins that are protective can subsequently be tested in humans. Amongst the
      immunodominant antigens some were predominantly recognized by sera from macaques
      inoculated in the fallopian tubes rather than in the cervix and therefore, may be
      markers for upper genital tract pathology. In addition, treatment with
      doxycycline following infection significantly decreased Chlamydia-specific
      antibody levels. This information can be used to evaluate the efficacy of
      antibiotic treatment and potentially susceptibility to reinfection.

PMID- 24862990
TI  - Involvement of abscisic acid and salicylic acid in signal cascade regulating
      bacterial endophyte-induced volatile oil biosynthesis in plantlets of
      Atractylodes lancea.
AB  - The enormous biological diversity of endophytes, coupled with their potential to
      enhance the production of bioactive metabolites in plants, has driven research
      efforts focusing on endophytes. However, limited information is available on the
      impacts of bacterial endophytes on plant secondary metabolism and signaling
      pathways involved. This work showed that an endophytic Acinetobacter sp. ALEB16,
      capable of activating accumulation of plant volatile oils, also induced abscisic
      acid (ABA) and salicylic acid (SA) production in Atractylodes lancea. Pre
      treatment of plantlets with biosynthetic inhibitors of ABA or SA blocked the
      bacterium-induced volatile production. ABA inhibitors suppressed not only the
      bacterium-induced volatile accumulation but also the induced ABA and SA
      generation; nevertheless, SA inhibitors did not significantly inhibit the induced
      ABA biosynthesis, implying that SA acted downstream of ABA production. These
      results were confirmed by observations that exogenous ABA and SA reversed the
      inhibition of bacterium-induced volatile accumulation by inhibitors.
      Transcriptional activities of genes in sesquiterpenoid biosynthesis also
      increased significantly with bacterium, ABA and SA treatments. Mevalonate pathway
      proved to be the main source of isopentenyldiphosphate for bacterium-induced
      sesquiterpenoids, as assessed in experiments using specific terpene biosynthesis
      inhibitors. These results suggest that Acinetobacter sp. acts as an endophytic
      elicitor to stimulate volatile biosynthesis of A. lancea via an ABA/SA-dependent
      pathway, thereby yielding additional insight into the interconnection between ABA
      and SA in biosynthesis-related signaling pathways. 

PMID- 24862991
TI  - Guest editorial: development of palliative care in long term-care facilities: a
      new evidence base.

PMID- 24862992
TI  - Learning, support and communication for staff in care homes: outcomes of
      reflective debriefing groups in two care homes to enhance end-of-life care.
AB  - BACKGROUND: Nursing care homes are increasingly the place where frail older
      people die. However, training in end-of-life care is not statutory. AIMS AND
      OBJECTIVES: To develop strategies to promote quality end-of-life care in nursing
      care homes. DESIGN: Action research was used to work collaboratively with the
      managers and staff in two nursing care homes to develop end-of-life care.
      METHODS: There were three overarching phases: an exploratory phase,
      feedback/planning of actions and a summative evaluation. Two main actions were
      inductively derived. One of the actions, reflective debriefing groups following a
      resident's death, is reported. RESULTS: Ten reflective debriefing groups, led by
      the researcher (a specialist palliative care nurse), were undertaken. The groups
      facilitated learning at three different levels (being taught, developing
      understanding and critical thinking) and enabled staff to feel supported and
      valued. IMPLICATIONS FOR PRACTICE: The use of reflective debriefing groups is a
      useful mechanism to support experience-based learning about death/dying in care
      homes.

PMID- 24862993
TI  - Ethics and gender issues in palliative care in nursing homes: an Austrian
      participatory research project.
AB  - BACKGROUND: The development of palliative care in nursing homes in German
      speaking countries has gained in importance within the past 15-20 years. Ethical
      and gender issues are core aspects of a palliative care culture and should
      therefore be better understood. AIMS AND OBJECTIVES: The aim of this study was to
      highlight insights regarding ethical and gender issues, based on the experiences
      of professionals in nursing homes. DESIGN: A 2-year participatory action research
      study was performed in collaboration with three nursing homes in Austria.
      METHODS: The article focusses on 10 group discussions with interdisciplinary
      professional teams that were conducted to generate ethical narratives. Thematic
      and narrative analysis was undertaken both individually and within the
      interdisciplinary research team. Findings and interpretations were validated with
      practitioners and researchers. FINDINGS: A total of 36 narratives were collected
      and summarised within eight themes concerning the theoretical journey of a
      nursing home resident with relatives from entry into the house until death. The
      most burdensome ethical dilemmas are not the ones around death and dying but
      rather those relating to small-scale everyday work/life issues. Sharing
      experiences and feelings in ethical discussions provides relief. Emotions are
      important facilitators of insight into ethical dilemmas. Gender issues can be
      observed in care situations as well as in the organisational structure of nursing
      homes. CONCLUSIONS: Opportunities to share experiences and perspectives around
      ethical questions in interdisciplinary group discussions help professionals to
      better understand difficult issues and find appropriate ways of managing them.
      IMPLICATIONS FOR PRACTICE: There is a need for communication structures such as
      facilitated ethical discussions that enable nursing home staff to reflect their
      everyday decisions. Expression of emotions should be encouraged in ethical
      decision-making processes in nursing homes. Gender-sensitive reflection supports
      the development of palliative care as organisational culture.

PMID- 24862995
TI  - Re: Correction of intramural ureteral ectopia.

PMID- 24862996
TI  - Is Mycoplasma bovis a missing component of the bovine respiratory disease complex
      in Australia?
AB  - BACKGROUND: Bovine respiratory disease complex (BRDC) is a multi-factorial
      disease in which numerous factors, such as animal management, pathogen exposure
      and environmental conditions, contribute to the development of acute respiratory
      illness in feedlot cattle. The role of specific pathogens in the development of
      BRDC has been difficult to define because of the complex nature of the disease
      and the presence of implicated bacterial pathogens in the upper respiratory tract
      of healthy animals. Mycoplasma bovis is an important pathogen of cattle and
      recognised as a major contributor to cases of mastitis, caseonecrotic
      bronchopneumonia, arthritis and otitis media. To date, the role of M. bovis in
      the development of BRDC of Australian feeder cattle has not been investigated.
      METHODS: In this review, the current literature pertaining to the role of M.
      bovis in BRDC is evaluated. In addition, preliminary data are presented that
      identify M. bovis as a potential contributor to BRDC in Australian feedlots,
      which has not been considered previously. RESULTS AND CONCLUSION: The preliminary
      results demonstrate detection of M. bovis in samples from all feedlots studied.
      When considered in the context of the reviewed literature, they support the
      inclusion of M. bovis on the list of pathogens to be considered during
      investigations into BRDC in Australia.

PMID- 24862998
TI  - Survey on the occurrence of milk fever in dairy cows and the current preventive
      strategies adopted by farmers in New South Wales, Australia.
AB  - OBJECTIVE: The aim of this study was to investigate general and specific
      strategies adopted by New South Wales (NSW) farmers to prevent milk fever (MF)
      and its occurrence at calving within their dairy herds. DESIGN AND METHODS: Of
      300 dairy farmers in NSW randomly chosen and sent questionnaires, descriptive
      analysis of the returned data was performed for 102 questionnaires. To identify
      the various strategies used to prevent MF and its incidence, farms were
      classified as having a low (<3%) or high (>3%) incidence of MF. The data were
      analysed using a multivariable logistic regression model and backwards stepwise
      elimination to identify significant preventive strategies adopted by farmers
      having a low or high incidence of MF. RESULTS: Based on the 102 responses, the
      median incidence of MF in the NSW dairy region was 3% (range 0-30%). The farms
      with low MF incidence practised specific MF control strategies, such as feeding
      dry cows separately, grain supplementation and feeding a low-potassium ration
      before calving and using a commercial ration mix immediately after calving. The
      time to first milking post-calving was on average 13.6 h on the low-incidence
      farms compared with 21.1 h on the high-incidence farms. CONCLUSIONS: The low
      median incidence of MF (3%) in NSW was probably related in part to awareness of
      the importance of feeding a low-potassium, high-grain diet before calving.
      However, the incidence of MF was high on the farms not practising specific MF
      preventive methods.

PMID- 24862997
TI  - Development and validation of a 3ABC antibody ELISA in Australia for foot and
      mouth disease.
AB  - OBJECTIVE: To measure the diagnostic performance of an Australian-developed ELISA
      for the detection of antibodies against the non-structural proteins (NSP) 3ABC of
      the foot and mouth disease (FMD) virus. DESIGN: Test development and validation
      study. METHODS: The diagnostic specificity was determined using 2535 sera from
      naive animals and 1112 sera from vaccinated animals. Diagnostic sensitivity was
      calculated from the data for 995 sera from experimentally and field-infected
      animals from FMD-endemic countries in South East Asia. A commercial ELISA
      detecting antibodies against FMD virus NSP was used as the reference test to
      establish relative sensitivity and specificity. Bayesian latent class analysis
      was performed to corroborate results. The diagnostic window and rate of detection
      were determined at different times using sera from cattle, sheep and pigs before
      and after infection, and after vaccination and subsequent infection.
      Repeatability and reproducibility data were established. RESULTS: At 35% test cut
      off, the 3ABC ELISA had an overall diagnostic sensitivity of 91.5% and diagnostic
      specificity of 96.4%. The diagnostic sensitivity in vaccinated and subsequently
      infected cattle was 68.4% and diagnostic specificity in vaccinated cattle was
      98.0%. CONCLUSIONS: The 3ABC ELISA identified field and experimentally infected
      animals, as well as vaccinated and subsequently infected animals. Diagnostic
      sensitivity and specificity estimates for other FMD NSP tests are comparable with
      the results obtained in this study. This NSP ELISA was found to be 'fit for
      purpose' as a screening assay at the herd level to detect viral infection and
      also to substantiate absence of infection.

PMID- 24863000
TI  - Prevalence of desexed cats in relation to age in a convenience sample of Western
      Australian cats.
AB  - BACKGROUND: Desexing percentages for pet cats in Australia are nearly 95%, but
      the high numbers of unwanted kittens surrendered to animal shelters suggest that
      many pet cats breed before the owners consider desexing, or that the mothers of
      many of these kittens are stray or feral. METHODS AND RESULTS: A convenience
      sample of Western Australian pet cats of known age presented for microchipping
      (584 in 2012 and 316 in 2013) found that younger cats were less likely to be
      desexed. In 2012, 93.2% of cats aged >=2 years were desexed compared with 49.4%
      of cats <2 years old, with the data for 2013 being 97.4% and 28%, respectively.
      CONCLUSION: If these results are reflected nationally, desexing of prepubescent
      cats up to 4 months old could significantly reduce the numbers of unwanted
      kittens born to pet cats.

PMID- 24862999
TI  - Storage mite contamination of commercial dry dog food in south-eastern Australia.
AB  - OBJECTIVE: To evaluate contamination of unopened and opened stored sources of
      commercial dry dog food by viable storage mites. DESIGN: Prospective laboratory
      and field study. MATERIAL AND METHODS: Samples were collected from nine brands of
      previously unopened bags (new bags) of dry food and 20 field sources of stored
      dry food in homes in Sydney and Canberra, Australia. All samples were initially
      examined for the presence of mites using a stereo-binocular microscope and then
      placed in separate filter-paper-sealed containers. Field samples were incubated
      at an average temperature of 29 degrees C and 78% relative humidity (RH) for 5
      weeks and then at average 26 degrees C/83% RH for 8 weeks. Paired new-bag samples
      were stored under room conditions (average 23 degrees C/47% RH) and controlled
      incubator conditions (average 26 degrees C/80% RH) for 6 weeks. All samples were
      thoroughly examined for mites, mite eggs and visible mould once weekly using a
      stereo-binocular microscope. RESULTS: Storage mites were not visualised in any of
      the field samples or in new-bag samples stored at room temperature. Storage
      mites, identified as Tyrophagus putrescentiae, were visualised in increasing
      numbers in seven of nine new-bag samples after incubation, with first mites and
      then eggs evident after 3 weeks of incubation. CONCLUSIONS: We confirmed the
      presence of viable storage mites in a range of previously unopened commercial dry
      dog foods in Australia and confirmed the possibility of heavy storage mite
      contamination for dry food stored under conditions of moderate temperature and
      high humidity. These findings have relevance to storage mite and/or dust mite
      sensitivity in canine atopic dermatitis.

PMID- 24863001
TI  - New research examining the effect of euthanasia on the mental health of
      veterinarians.

PMID- 24863002
TI  - The origin of the room-temperature stability of [TTF]+???[TTF]+ long, multicenter
      bonds found in functionalized pi-[R-TTF]22+ dimers included in the
      cucurbit[8]uril cavity.
AB  - A computational study is performed to identify the origin of the room-temperature
      stability, in aqueous solution, of functionalized pi-[R-TTF]2(2+) dimers
      (TTF=tetrathiafulvalene; R=(CH2OCH2)5CH2OH) included in the cavity of a
      cucurbit[8]uril (CB[8]) molecule. pi-[R-TTF]2(2+) dimers in pure water are weakly
      stable, and are mostly dissociated at room temperature. Upon addition of CB[8] to
      an aqueous pi-[R-TTF]2(2+) solution, a (pi-[R-TTF]2?CB[8])(2+) inclusion complex
      is formed. The same complex is obtained after the sequential inclusion of two [R
      TTF](.+) monomers in the CB[8] molecule. Both processes are thermodynamically and
      kinetically allowed. pi-[R-TTF]2(2+) dimers dissolved in pure water present a
      [TTF](.+)???[TTF](.+) long, multicenter bond, similar to that already identified
      in pi-[TTF]2(2+) dimers dissolved in organic solvents. Upon their inclusion in
      CB[8], the strength and other features of the [TTF](.+)???[TTF](.+) long,
      multicenter bond are preserved. The room temperature stability of the pi-[R
      TTF]2(2+) dimers included in CB[8] is shown to originate in the pi-[R
      TTF]2(2+)???CB[8] interaction, the strength of which comes from a strongly
      attractive electrostatic component and a dispersion component. Such a dominant
      electrostatic term is caused by the strongly polarized charge distribution in
      CB[8], the geometrical complementarity of the pi-[R-TTF]2(2+) and CB[8]
      geometries, and the amplifying effect of the 2+ charge in pi-[R-TTF]2(2+).

PMID- 24863003
TI  - Prospective observational study on diagnostic accuracy of whole-body MRI in solid
      small round cell tumours.
AB  - AIM: To assess the diagnostic accuracy of whole-body magnetic resonance imaging
      (WB-MRI) for metastatic disease in patients with solid small round cell tumours
      (SRCT) by comparing it with routine staging procedures (standard of care).
      MATERIALS AND METHODS: Eligible cases of neuroblastoma, primitive neuroectodermal
      tumour, and rhabdomyosarcoma were enrolled in the study after obtaining informed
      consent. WB-MRI was undertaken using overlapping coronal T1 and short-tau
      inversion recovery (STIR) sequences. Lesions were classified into skeletal,
      pulmonary, and soft-tissue types. Conventional staging, which consisted of
      combined positron-emission tomography & computed tomography (PET-CT), bone
      scintigraphy & bone marrow biopsy for bone metastases, CT thorax for lung
      metastases, combined PET-CT, metaiodobenzylguanidine (MIBG) scintigraphy (in
      neuroblastoma) for soft tissue metastases and clinical evaluation was used as the
      reference standard. Parameters for diagnostic accuracy were calculated. RESULTS:
      Thirty-four out of forty patients enrolled were included in final analysis, half
      of them having metastatic disease. The sensitivity, specificity, positive and
      negative predictive value, and the diagnostic accuracy of WB-MRI and PET-CT for
      skeletal metastases as compared to reference standard were 91.9%, 99.8%, 97.4%,
      99.6%, and 95.5% and 99.1%, 99.9%, 99.1%, 99.9%, and 99.9%, respectively. The
      sensitivity of MRI, only PET and PET-CT with plain CT thorax was 30%, 40%, and
      100%, respectively, for lung metastases. The sensitivity of MRI for soft-tissue
      lesions was 76.9%. CONCLUSION: WB-MRI is a radiation-free tool with high
      diagnostic accuracy for the evaluation of metastatic disease to the marrow. The
      rate of detection of soft-tissue metastases, such as nodal metastases, is less
      when WB-MRI is compared with conventional staging using coronal STIR images. CT
      thorax is essential for accurate evaluation of lung metastases.

PMID- 24863004
TI  - MicroRNA expression profiling of thymic epithelial tumors.
AB  - BACKGROUND: Thymic epithelial tumors (TET) are the most frequent human primary
      mediastinal tumors in adults. A deep biological characterization of the processes
      at the basis of the transformed phenotype could strongly improve our
      understanding of the morphological and clinical heterogeneity of these diseases.
      MicroRNAs (miRNAs) are non-coding RNAs involved in post-transcriptional
      regulation and their altered expression accounts for the pathogenesis of several
      tumors. OBJECTIVES: The aim of this study was to identify the miRNAs that are
      differentially expressed in tumor vs normal thymic tissues or among the different
      tumor histotypes and that could impact on the biology of TET. MATERIALS AND
      METHODS: microRNAs expression profiling was performed by microarray analysis of
      formalin-fixed paraffin embedded (FFPE) tissue from 54 thymic tumor samples and
      12 normal counterparts, derived from two patient cohorts. RESULTS AND CONCLUSION:
      We identified groups of miRNAs differentially expressed between: (i) TET and
      normal thymic tissues, (ii) thymomas and thymic carcinomas, (iii) histotype
      groups. Moreover, we identified putative molecular pathways targeted by these
      differentially expressed miRNAs that could be involved in thymic carcinogenesis
      and in the maintenance and spreading of this tumor.

PMID- 24863005
TI  - KRAS oncogene substitutions in Korean NSCLC patients: clinical implication and
      relationship with pAKT and RalGTPases expression.
AB  - OBJECTIVES: Since different conformation of each KRAS mutant leads to inherent
      downstream signaling, its distribution, influence on the clinical outcome, and
      effect on the signaling mediators were investigated in the Korean NSCLC patients
      whose tumor have KRAS mutation. MATERIALS AND METHODS: Mutation at KRAS codons 12
      and 13 was evaluated in 1420 Korean NSCLC by direct sequencing and expression of
      RalA, RalB, and pAKT-Ser473 was evaluated by immunohistochemistry in 30 cases
      whose KRAS mutant tumor tissues were available. RESULTS: Eighty-two (5.8%) out of
      1420 patients harbored a KRAS mutation either in codon 12 or 13. Gly12Asp was the
      most frequent (34.1%), followed by Gly12Cys (22.0%) and Gly12Val (13.4%).
      Transversion at codons 12 and 13, which includes Gly12Cys, Gly12Val, Gly12Ala,
      Gly13Cys, and Gly12Phe was detected in 45 cases (54.9%) and transition, including
      Gly12Asp, Gly12Ser, and Gly13Asp was detected in 37 cases (45.1%). Male and
      smoking history were associated with transversion (p=0.001 and 0.006,
      respectively; chi(2)-test), and multivariate analysis showed that gender was an
      independent influencing factor (p=0.026; Cochran-Mantel-Haenszel test).
      Multivariate analysis on survival revealed that KRAS mutation subtype did not
      influence overall survival of the patients with KRAS mutations after adjustment
      for age, gender, performance status, and stage. There were no differences in the
      nuclear and cytoplasmic expression of pAKT-Ser473 between transversion and
      transition mutants. Expression of Ral-GTPases, RalA and RalB, did not differ
      between transversion and transition mutants, however, strong expression of RalB
      in the tissue of patients with KRAS mutants was associated with advanced stages
      (P-value=0.020, chi(2)-test). CONCLUSIONS: In this study population, not only the
      frequency of KRAS mutation but also the distribution of its subtypes differed
      from those of Western studies, with unique influencing factors. Clinical outcome
      and expression of pAKT-Ser473, RalA, and RalB did not differ among subtypes.

PMID- 24863006
TI  - Clinical and magnetic resonance imaging characteristics of tubercular
      ventriculitis: an under-recognized complication of tubercular meningitis.
AB  - BACKGROUND: Ventriculitis also referred as ependymitis or ventricular empyema is
      a known complication of pyogenic meningitis. Despite high incidence of tubercular
      meningitis in developing countries, there are hardly any reports of tubercular
      ventriculitis. METHODS: Five patients (four males and one female) of tubercular
      ventriculitis were retrospectively identified from December 2007 to August 2013.
      Their clinical features, cranial MRI characteristics, treatment offered, and
      outcome were reviewed. RESULTS: The median age of 5 patients was 29 years (range
      15 to 64 years). Two patients had preceding pulmonary/pleural tuberculosis and
      one had Pott's spine. One patient had multi-drug resistant tuberculosis. All five
      patients had papilledema, four had seizures, two had hemiparesis, and two had
      vision loss. On cranial MRI all patients showed contrast enhancement of ependymal
      wall of lateral/fourth ventricle with restricted diffusion and hydrocephalus;
      three showed intra-ventricular septations with sequestered ventricles, and two
      had ventricular sludge. Magnetization transfer (MT) images were available in only
      two patients. Both showed hyperintense epedymal wall on MT images. Four patients
      required ventriculo-peritoneal shunt and two underwent temporal lobectomy. Two
      patients with sequestered temporal lobe had acute deterioration in consciousness
      with signs of impending herniation and required urgent surgical intervention.
      Four patients recovered on anti-tubercular treatment over 18 months; one
      receiving secondary line ATT for residual brain abscess. CONCLUSION: Tubercular
      ventriculitis is a rare complication of tubercular meningitis. MRI feature of
      sequestered ventricles/intraventricular septations and hyperintense ependymal
      wall on MT images could suggest tubercular etiology. Symptomatic hydrocephalus
      may require CSF diversion in most patients.

PMID- 24863007
TI  - An adult case of cerebral malakoplakia successfully cured by treatment with
      antibiotics, bethanechol and ascorbic acid.
AB  - Cerebral malakoplakia is a very rare chronic inflammatory disease. We herein
      report the case of a 49-year-old female who presented with a slowly progressive
      speech disturbance and right hemiparesis. Computed tomography and magnetic
      resonance imaging showed irregular enhanced mass lesions with numerous scattered
      areas of calcification in the left insula, thalamus and basal ganglia.
      Histopathologically, the biopsy specimen showed basophilic laminated inclusion
      bodies and intracellular and extracellular calculospherules, usually with a
      typical targetoid appearance (Michaelis-Gutmann bodies). Treatment with
      antibiotics, bethanechol and ascorbic acid improved her symptoms in association
      with a decrease in the abnormal calcification and enhancement. The cerebral
      malakoplakia mimicked a brain tumor in terms of the patient's clinical course and
      neuroradiological image findings; however, it was successfully cured with medical
      treatment. This case provides evidence that the pathogenesis of cerebral
      malakoplakia is deeply tied to bacterial infection and that medical treatment is
      effective in cases of this disease. 

PMID- 24863008
TI  - Reporting thyroid FNA before and after implementation of the Bethesda system-one
      institution's experience.
AB  - BACKGROUND: The Bethesda System for Reporting Thyroid Cytopathology was published
      in 2008 and was implemented at Beth Israel Deaconess Medical Center (BIDMC) in
      June, 2010. Prior to this date, our diagnostic scheme was similar to the Bethesda
      System, except for the category of "Atypia/Follicular Lesion of Undetermined
      Significance" (AUS). This study evaluates the impact of the Bethesda System on
      the rate and the positive predictive value (PPV) of the diagnostic categories at
      BIDMC. METHODS: We performed a retrospective review of all thyroid fine-needle
      aspirations (FNAs) during the time periods January, 2006 to November, 2008 and
      June, 2010 to July, 2011 and the subsequent thyroidectomy specimens. RESULTS:
      Post-Bethesda System, diagnoses that are equivocal for diverse reasons and which
      have wide-ranging PPVs are now all grouped into the AUS category, and the
      proportion of cases that are in the atypical/AUS category rose from 3.7% in the
      pre-Bethesda period to 12% in the post-Bethesda period. CONCLUSION: The AUS
      category has a PPV approaching 50% in our lab. This creates uncertainty regarding
      the appropriate management for this category and may cause unnecessary overuse of
      molecular testing for cases in the AUS category.

PMID- 24863009
TI  - Antiretroviral therapy effects on sources of cortical rhythms in HIV subjects:
      responders vs. mild responders.
AB  - OBJECTIVE: We tested the hypothesis that 5months of combined anti-retroviral
      therapy (cART) affect cortical sources of resting state cortical
      electroencephalographic (EEG) rhythms in naive HIV subjects. METHODS: Eyes-closed
      resting state EEG data were recorded at baseline (i.e. pre-treatment; T0), T1
      (after 4weeks of cART), T2 (after 8weeks of cART), and T5 (after 5months of cART)
      in 38 naive HIV subjects. EEG data were also recorded in 40 age-matched
      cognitively normal subjects for control purposes. EEG rhythms of interest were
      delta (2-4Hz), theta (4-8Hz), alpha 1 (8-10.5Hz), alpha 2 (10.5-13Hz), beta 1 (13
      20Hz), and beta 2 (20-30Hz). Cortical EEG sources were estimated by LORETA
      software. RESULTS: Compared to the control group, the HIV group at T0 showed
      greater delta sources and lower widespread alpha sources. cART induced a global
      improvement of biological (viral load, CD4 count) and EEG (delta, alpha) markers,
      remarkable even after 4weeks. Compared to HIV Responders (>100cells/MUl at 5
      month follow up), the HIV Mild Responders (<100cells/MUl) showed greater parietal
      delta sources at baseline and lower occipital alpha sources at 5-month follow up.
      CONCLUSIONS: In naive HIV subjects, 5months of successful cART affect brain
      synchronization mechanisms at the basis of the generation of delta and alpha
      rhythms. SIGNIFICANCE: The present EEG markers may be useful secondary
      neurophysiological end points for pharmacological clinical trials in naive HIV
      subjects.

PMID- 24863010
TI  - On compensatory strategies and computational models: the case of pure alexia.
AB  - The article is concerned with inferences from the behaviour of neurological
      patients to models of normal function. It takes the letter-by-letter reading
      strategy common in pure alexic patients as an example of the methodological
      problems involved in making such inferences that compensatory strategies produce.
      The evidence is discussed on the possible use of three ways the letter-by-letter
      reading process might operate: "reversed spelling"; the use of the phonological
      input buffer as a temporary holding store during word building; and the use of
      serial input to the visual word-form system entirely within the visual
      orthographic domain such as in the model of Plaut [1999. A connectionist approach
      to word reading and acquired dyslexia: Extension to sequential processing.
      Cognitive Science, 23, 543-568]. The compensatory strategy used by, at least, one
      pure alexic patient does not fit with the third of these possibilities. On the
      more general question, it is argued that even if compensatory strategies are
      being used, the behaviour of neurological patients can be useful for the
      development and assessment of first-generation information-processing models of
      normal function, but they are not likely to be useful for the development and
      assessment of second-generation computational models.

PMID- 24863011
TI  - Risk factors of early and late mortality after thoracic endovascular aortic
      repair for complicated stanford B acute aortic dissection.
AB  - BACKGROUND AND AIM OF THE STUDY: The risk factors associated with death in
      complicated Stanford B acute aortic dissection (AAD) after thoracic endovascular
      aortic repair (TEVAR) are poorly understood. The aim of this study was to
      evaluate the early and late events and mortality of complicated Stanford B AAD
      associated with TEVAR. METHODS: Sixty-two patients with complicated Stanford B
      AAD undergoing TEVAR were included in this study. RESULTS: Primary technical
      success of TEVAR was achieved in 61 (98.39%) cases. The early mortality rate was
      9.68%. Procedural type I endoleak (p = 0.007, OR = 7.71, 95% CI: 1.75-34.01) and
      cardiac tamponade (p = 0.010, OR = 8.86, 95% CI: 1.70-4 6.14) were the
      significant predictors of early death in the multivariate model. The late
      mortality was 16.07%. Cox regression analysis revealed rupture of false lumen (p
      = 0.001, hazard ratio = 21.96, 95% CI: 3.02-82.12), postoperative myocardial
      infarction (p = 0.001, hazard ratio = 9.86, 95% CI: 2.12-39.64), and acute renal
      failure (p = 0.024, hazard ratio = 3.98, 95% CI: 1.26-12.11) to be independent
      risk factors of late mortality. CONCLUSIONS: Type I procedural endoleak and
      cardiac tamponade were the significant predictors of early death in patients of
      complicated Stanford B AAD undergoing TEVAR. Rupture of false lumen,
      postoperative myocardial infarction, and acute renal failure were the independent
      risk factors for late death after TEVAR.

PMID- 24863012
TI  - Extending network approach to language dynamics and human cognition: comment on
      "approaching human language with complex networks" by Cong and Liu.

PMID- 24863013
TI  - Comparing 3-T multiparametric MRI and the Partin tables to predict organ-confined
      prostate cancer after radical prostatectomy.
AB  - OBJECTIVES: The purpose of our study was to test our hypothesis that
      multiparametric magnetic resonance imaging (mpMRI) may have a higher prognostic
      accuracy than the Partin tables in predicting organ-confined (OC) prostate cancer
      and extracapsular extension (ECE) after radical prostatectomy (RP). METHODS AND
      MATERIALS: After institutional review board approval, we retrospectively reviewed
      60 patients who underwent 3-T mpMRI before RP. mpMRI was used to assess clinical
      stage and the updated version of the Partin tables was used to calculate the
      probability of each patient to harbor OC disease. Sensitivity, specificity,
      positive predictive value (PPV), and negative predictive value (NPV) of mpMRI in
      detecting OC and ECE were calculated. Logistic regression models predicting OC
      pathology were created using either clinical stage at mpMRI or Partin tables
      probability. The area under the curve was used to calculate the predictive
      accuracy of each model. RESULTS: Median prostate-specific antigen level at
      diagnosis was 5 ng/ml (range: 4.1-6.7 ng/ml). Overall, 52 (86.7%) men had cT1
      disease, 7 (11.7%) had cT2a/b, and 1 (1.6%) had cT3b at digital rectal
      examination. Biopsy Gleason score was 6, 3+4 = 7, 4+3 = 7, 8, and 9 to 10 in 28
      (46.7%), 15 (25%), 3 (5%), 10 (16.7%), and 4 (6.6%) patients, respectively. At
      mpMRI, clinical stage was defined as cT2a/b, cT2c, cT3a, and cT3b in 11 (18.3%),
      23 (38.3%), 21 (35%), and 5 (8.4%) patients, respectively. At final pathology, 38
      men (63.3%) had OC disease, whereas 18 (30%) had ECE and 4 (6.7%) had seminal
      vesicle invasion. The sensitivity, specificity, PPV, and NPV of mpMRI in
      detecting OC disease were 81.6%, 86.4%, 91.2%, and 73.1%, respectively, whereas
      in detecting ECE were 77.8%, 83.4%, 66.7%, and 89.7%, respectively. At logistic
      regression, both the Partin tables-derived probability and the mpMRI clinical
      staging were significantly associated with OC disease (all P<0.01). The area
      under the curves of the model built using the Partin tables and that of the mpMRI
      model were 0.62 and 0.82, respectively (P = 0.04). CONCLUSIONS: The predictive
      accuracy of mpMRI in predicting OC disease on pathological analysis is
      significantly greater than that of the Partin tables. mpMRI had a high PPV
      (91.2%) when predicting OC disease and a high NPV (89.7%) with regard to ECE.
      mpMRI should be considered when planning prostate cancer treatment in addition to
      readily available clinical parameters.

PMID- 24863014
TI  - National trends in the utilization of robotic-assisted radical cystectomy: an
      analysis using the Nationwide Inpatient Sample.
AB  - OBJECTIVES: To determine temporal and regional trends in utilization of robotic
      assisted radical cystectomy (RARC) in the United States and to explore factors
      associated with utilization of robotic assistance. MATERIALS AND METHODS: Using
      2009 to 2011 data from the Nationwide Inpatient Sample, we identified radical
      cystectomy cases that were performed using either open or robotic assistance and
      applied Nationwide Inpatient Sample discharge weights to determine national
      incidence. Univariable and multivariable logistic regressions were performed to
      assess regional trends and characteristics associated with having RARC.
      Descriptive analysis was performed using the chi-square test, the Student t test,
      and the Mann-Whitney U test. RESULTS: Of the 29,719 radical cystectomy patients,
      3,733 were RARC (12.6%). Although there was no change in the proportion of RARC
      performed annually (P = 0.702). Length of stay was 1 day longer for open
      cystectomy than RARC (P<0.001). On multivariate regression, patients whose
      primary payer was Medicaid were less likely than private insurance patients to
      undergo RARC (odds ratio = 0.60, P = 0.074). Additionally, patients in the south
      were at 50% reduced odds of undergoing RARC (odds ratio = 0.49, P = 0.044).
      Median hospital costs were $5,000 greater for RARC (P<0.001). CONCLUSIONS:
      Regional variation in utilization should be monitored to ensure equal access to
      new technology and to assess potential overuse of new technology. Although RARC
      is associated with higher median hospital costs, further studies to assess its
      benefits are warranted.

PMID- 24863015
TI  - The problem of severe valve prosthesis-patient mismatch in aortic bioprostheses:
      near extinction?

PMID- 24863016
TI  - Going beyond right and wrong: building the framework for quality improvement in
      congenital echocardiography--you can't manage what you don't measure.

PMID- 24863017
TI  - Reminiscing... success and challenge in 2013-2014.

PMID- 24863018
TI  - Legal issues for the cardiovascular sonographer.

PMID- 24863019
TI  - Pediatric and congenital echocardiography: looking into the future.

PMID- 24863021
TI  - Shoulder dystocia and neonatal brachial plexus palsy: eliminating the nightmare.

PMID- 24863020
TI  - Semi-quantitative monitoring of confluence of adherent mesenchymal stromal cells
      on calcium-phosphate granules by using widefield microscopy images.
AB  - The analysis of cell confluence and proliferation is essential to design
      biomaterials and scaffolds to use as bone substitutes in clinical applications.
      Accordingly, several approaches have been proposed in the literature to estimate
      the area of the scaffold covered by cells. Nevertheless, most of the approaches
      rely on sophisticated equipment not employed for routine analyses, while the rest
      of them usually do not provide significant statistics about the cell
      distribution. This research aims at studying confluence and proliferation of
      mesenchymal stromal cells (MSC) adherent on OSPROLIFE((r)), a commercial
      biomaterial in the form of granules. In particular, we propose a Computer Vision
      approach that can routinely be employed to monitor the surface of the single
      granules covered by cells because only a standard widefield fluorescent
      microscope is required. In order to acquire significant statistics data, we
      analyse wide-area images built by using MicroMos v2.0, an updated version of a
      previously published software specific for stitching brightfield and phase
      contrast images manually acquired via a widefield microscope. In particular,
      MicroMos v2.0 permits to build accurate "mosaics" of fluorescent images, after
      correcting vignetting and photo-bleaching effects, providing a consistent
      representation of a sample region containing numerous granules. Then, our method
      allows to make automatically a statistically significant estimate of the
      percentage of the area of the single granules covered by cells. Finally, by
      analysing hundreds of granules at different time intervals we also obtained
      reliable data regarding cell proliferation, confirming that not only MSC adhere
      onto the OSPROLIFE((r)) granules, but even proliferate over time. 

PMID- 24863022
TI  - Shoulder dystocia: definitions and incidence.
AB  - Though subjective in nature, both the American College of Obstetricians and
      Gynecologists practice bulletin and the Royal College of Obstetricians and
      Gynaecologists green guideline are in agreement on the descriptor of shoulder
      dystocia: requirement of additional obstetric maneuvers when gentle downward
      traction has failed to affect the delivery of the shoulders. The rate of shoulder
      dystocia is about 1.4% of all deliveries and 0.7% for vaginal births. Compared to
      non-diabetics (0.6%), among diabetics, the rate of impacted shoulders is 201%
      higher (1.9%); newborns delivered by vacuum or forceps have 254% higher
      likelihood of shoulder dystocia than those born spontaneously (2.0% vs. 0.6%,
      respectively). When the birthweight is categorized as <4000, 4000-4449, and >4500
      g, the likelihood of shoulder dystocia in the US vs. other countries varies
      significantly. Future studies should focus on lowering the rate of shoulder
      dystocia and its associated morbidities, without concomitantly increasing the
      rate of cesarean delivery.

PMID- 24863023
TI  - Shoulder dystocia: risk factors, predictability, and preventability.
AB  - Shoulder dystocia remains an unpredictable obstetric emergency, striking fear in
      the hearts of obstetricians both novice and experienced. While outcomes that lead
      to permanent injury are rare, almost all obstetricians with enough years of
      practice have participated in a birth with a severe shoulder dystocia and are at
      least aware of cases that have resulted in significant neurologic injury or even
      neonatal death. This is despite many years of research trying to understand the
      risk factors associated with it, all in an attempt primarily to characterize when
      the risk is high enough to avoid vaginal delivery altogether and prevent a
      shoulder dystocia, whose attendant morbidities are estimated to be at a rate as
      high as 16-48%. The study of shoulder dystocia remains challenging due to its
      generally retrospective nature, as well as dependence on proper identification
      and documentation. As a result, the prediction of shoulder dystocia remains
      elusive, and the cost of trying to prevent one by performing a cesarean delivery
      remains high. While ultimately it is the injury that is the key concern, rather
      than the shoulder dystocia itself, it is in the presence of an identified
      shoulder dystocia that occurrence of injury is most common. The majority of
      shoulder dystocia cases occur without major risk factors. Moreover, even the best
      antenatal predictors have a low positive predictive value. Shoulder dystocia
      therefore cannot be reliably predicted, and the only preventative measure is
      cesarean delivery. 

PMID- 24863024
TI  - Shoulder dystocia: management and documentation.
AB  - Shoulder dystocia is an obstetric emergency that occurs when the fetal shoulders
      become impacted at the pelvic inlet. Management is based on performing maneuvers
      to alleviate this impaction. A number of protocols and training mnemonics have
      been developed to assist in managing shoulder dystocia when it occurs. This
      article reviews the evidence regarding the performance, timing, and sequence of
      these maneuvers; reviews the mechanism of fetal injury in relation to shoulder
      dystocia; and discusses issues concerning documentation of the care provided
      during this obstetric emergency. 

PMID- 24863025
TI  - Complications of shoulder dystocia.
AB  - Complications of shoulder dystocia are divided into fetal and maternal. Fetal
      brachial plexus injury (BPI) is the most common fetal complication occurring in 4
      40% of cases. BPI has also been reported in abdominal deliveries and in
      deliveries not complicated by shoulder dystocia. Fractures of the fetal humerus
      and clavicle occur in about 10.6% of cases of shoulder dystocia and usually heal
      with no sequel. Hypoxic ischemic brain injury is reported in 0.5-23% of cases of
      shoulder dystocia. The risk correlates with the duration of head-to-body delivery
      and is especially increased when the duration is >5 min. Fetal death is rare and
      is reported in 0.4% of cases. Maternal complications of shoulder dystocia include
      post-partum hemorrhage, vaginal lacerations, anal tears, and uterine rupture. The
      psychological stress impact of shoulder dystocia is under-recognized and deserves
      counseling prior to home discharge.

PMID- 24863026
TI  - Shoulder dystocia: simulation and a team-centered protocol.
AB  - Shoulder dystocia is an obstetric emergency that has been reported to occur in
      0.2-3% of all vaginal deliveries. Several characteristics of shoulder dystocia
      make it a particular challenge to manage effectively. It is relatively
      infrequent, the diagnosis cannot be made according to a single objective
      criterion that can be recognized to exist by all members of the care team who are
      present, it is unpredictable, and there is the need for coordinated actions of
      all members of the health care team who have come together on the day of the
      delivery and may not have worked together before or specifically during a
      shoulder dystocia. In general, there is evidence from different medical
      disciplines that checklists/protocols and simulation may be used to enhance team
      performance. There is also some evidence, albeit limited, that such techniques
      may be used to improve shoulder dystocia outcomes. 

PMID- 24863027
TI  - Neonatal brachial plexus palsy: incidence, prevalence, and temporal trends.
AB  - Epidemiological knowledge of the incidence, prevalence, and temporal changes of
      neonatal brachial plexuses palsy (NBPP) should assist the clinician, avert
      unnecessary interventions, and help formulate evidence-based health policies. A
      summary of 63 publications in the English language with over 17 million births
      and 24,000 NBPPs is notable for six things. First, the rate of NBPP in the US and
      other countries is comparable: 1.5 vs. 1.3 per 1000 total births, respectively.
      Second, the rate of NBPP may be decreasing: 0.9, 1.0 and 0.5 per 1,000 births for
      publications before 1990, 1990-2000, and after 2000, respectively. Third, the
      likelihood of not having concomitant shoulder dystocia with NBPP was 76% overall,
      though it varied by whether the publication was from the US (78%) vs. other
      countries (47%). Fourth, the likelihood of NBPP being permanent (lasting at least
      12 months) was 10-18% in the US-based reports and 19-23% in other countries.
      Fifth, in studies from the US, the rate of permanent NBPP is 1.1-2.2 per 10,000
      births and 2.9-3.7 per 10,000 births in other nations. Sixth, we estimate that
      approximately 5000 NBPPs occur every year in the US, of which over 580-1050 are
      permanent, and that since birth, 63,000 adults have been afflicted with
      persistent paresis of their brachial plexus. The exceedingly infrequent nature of
      permanent NBPP necessitates a multi-center study to improve our understanding of
      the antecedent factors and to abate the long-term sequela. 

PMID- 24863028
TI  - Risk factors for neonatal brachial plexus palsy.
AB  - Neonatal brachial plexus palsy (NBPP) is an unpredictable complication of
      childbirth. Historic risk factors for the occurrence of NBPP have included
      shoulder dystocia, fetal macrosomia, labor abnormalities, operative vaginal
      delivery, and prior NBPP. However, whether studied alone or in combination, these
      risk factors have not been shown to be reliable predictors. The majority of NBPP
      cases occur in women with infants <4500 g who are not diabetic and have no other
      identifiable risk factors. Furthermore, cesarean section reduces but does not
      completely eliminate the risk for NBPP. In this section, the relationship of
      these historic obstetric risk factors to the occurrence of NBPP is further
      explored.

PMID- 24863030
TI  - Use of immunohistochemistry in the diagnosis of miscellaneous and metastatic
      tumors of the uterine corpus and cervix.
AB  - Uncommon tumors in the uterus present diagnostic challenges. In some cases, the
      tumor subtype is usually seen outside the gynecologic tract and the possibility
      of a uterine primary is not considered. In other cases, histologic overlap with
      more common uterine tumors leads to potential misdiagnosis. Finally, metastatic
      carcinoma may involve the uterus and cervix. Rarely, symptoms related to the
      uterine metastasis may precede diagnosis of an extrauterine primary. Without the
      proper clinical context, the possibility of a missed diagnosis is increased. One
      must first be aware of these possibilities, but immunoperoxidase studies are
      often necessary to confirm the diagnosis. In this review, unusual and metastatic
      tumors involving the uterine corpus and cervix and immunoperoxidase studies used
      to diagnosis such tumors are discussed. 

PMID- 24863029
TI  - Neonatal brachial plexus palsy--management and prognostic factors.
AB  - Successful treatment of patients with neonatal brachial plexus palsy (NBPP)
      begins with a thorough understanding of the anatomy of the brachial plexus and of
      the pathophysiology of nerve injury via which the brachial plexus nerves
      stretched in the perinatal period manifest as a weak or paralyzed upper extremity
      in the newborn. NBPP can be classified by systems that can guide the prognosis
      and the management as these systems are based on the extent and severity of nerve
      injury, anatomy of nerve injury, and clinical presentation. Serial physical
      examinations, supplemented by a thorough maternal and perinatal history, are
      critical to the formulation of the treatment plan that relies upon
      occupational/physical therapy and rehabilitation management but may include nerve
      reconstruction and secondary musculoskeletal surgeries. Adjunctive imaging and
      electrodiagnostic studies provide additional information to guide prognosis and
      treatment. As research improves not only the technical aspects of NBPP treatment
      but also the ability to assess the activity and participation as well as body
      structure and function of NBPP patients, the functional outcomes for affected
      infants have an overall optimistic prognosis, with the majority recovering
      adequate functional use of the affected arm. Of importance are (i) early referral
      to interdisciplinary specialty clinics that can provide up-to-date advances in
      clinical care and (ii) increasing research/awareness of the psychosocial and
      patient-reported quality-of-life issues that surround the chronic disablement of
      NBPP. 

PMID- 24863031
TI  - Diagnostic use of immunohistochemistry in uterine mesenchymal tumors.
AB  - Immunohistochemistry may be helpful in the diagnosis of mesenchymal uterine
      tumors. This article reviews the immunoreactions used most frequently in the
      diagnosis of uterine smooth muscle tumors, endometrial stromal tumors,
      undifferentiated endometrial sarcomas, UTROSCTs, PEComas, adenomyomas,
      adenosarcomas and carcinosarcomas. 

PMID- 24863034
TI  - Large-scale analysis reveals a functional single-nucleotide polymorphism in the
      5'-flanking region of PRDM16 gene associated with lean body mass.
AB  - Genetic factors are important for the development of sarcopenia, a geriatric
      disorder characterized by low lean body mass. The aim of this study was to search
      for novel genes that regulate lean body mass in humans. We performed a large
      scale search for 250K single-nucleotide polymorphisms (SNPs) associated with bone
      mineral density (BMD) using SNP arrays in 1081 Japanese postmenopausal women. We
      focused on an SNP (rs12409277) located in the 5'-flanking region of the PRDM16
      (PRD1-BF-1-RIZ1 homologous domain containing protein 16) gene that showed a
      significant P value in our screening. We demonstrated that PRDM16 gene
      polymorphisms were significantly associated with total body BMD in 1081
      postmenopausal Japanese women. The rs12409277 SNP affected the transcriptional
      activity of PRDM16. The subjects with one or two minor allele(s) had a higher
      lean body mass than the subjects with two major alleles. Genetic analyses
      uncovered the importance of the PRDM16 gene in the regulation of lean body mass. 

PMID- 24863035
TI  - Identification during imposed change: the roles of personal values, type of
      change, and anxiety.
AB  - Using a person-situation perspective, we explain what happens to individuals'
      identification with a collective in the context of a change. We propose that
      given the anxiety that often emerges during change, individuals' personal values
      (conservation and openness to change) interact with type of change (imposed vs.
      voluntary) in predicting identification following change. In a pilot,
      longitudinal field study (N = 61, 67% female) of an imposed university campus
      relocation, we measured employees' values and identification with the university
      before and several months after the relocation. In two lab experiments (Study 1:
      N = 104, 91.3% female; Study 2: N = 113, 75.2% female), we manipulated a change
      to be either imposed or voluntary and compared the relationships between values
      and identification across types of change. In Study 2, we also measured anxiety
      from the change. When change was imposed (all three studies), but not when
      voluntary (Studies 1 and 2), individuals' conservation was positively, and
      openness negatively, related to individuals' post-change identification. The
      effects emerged only for individuals who experienced change-related anxiety
      (Study 2). Our findings demonstrate that individuals' identification with a
      changing collective depends on the amount of anxiety change elicits and on the
      particular combination of their values and type of change.

PMID- 24863036
TI  - Angoline: a selective IL-6/STAT3 signaling pathway inhibitor isolated from
      Zanthoxylum nitidum.
AB  - STAT3 signaling pathway is an important target for human cancer therapy. Thus,
      the identification of small-molecules that target STAT3 signaling will be of
      great interests in the development of anticancer agents. The aim of this study
      was to identify novel inhibitors of STAT3 pathway from the roots of Zanthoxylum
      nitidum (Roxb.) DC. The bioassay-guided fractionation of MeOH extract of Z.
      nitidum using a STAT3-responsive gene reporter assay led to the isolation of
      angoline (1) as a potent and selective inhibitor of the STAT3 signaling pathway
      (IC50=11.56 MUM). Angoline inhibited STAT3 phosphorylation and its target gene
      expression and consequently induced growth inhibition of human cancer cells with
      constitutively activated STAT3 (IC50=3.14-4.72 MUM). This work provided a novel
      lead for the development of anti-cancer agents targeting the STAT3 signaling
      pathway.

PMID- 24863032
TI  - Developmental perspectives on oxytocin and vasopressin.
AB  - The related neuropeptides oxytocin and vasopressin are involved in species
      typical behavior, including social recognition behavior, maternal behavior,
      social bonding, communication, and aggression. A wealth of evidence from animal
      models demonstrates significant modulation of adult social behavior by both of
      these neuropeptides and their receptors. Over the last decade, there has been a
      flood of studies in humans also implicating a role for these neuropeptides in
      human social behavior. Despite popular assumptions that oxytocin is a molecule of
      social bonding in the infant brain, less mechanistic research emphasis has been
      placed on the potential role of these neuropeptides in the developmental
      emergence of the neural substrates of behavior. This review summarizes what is
      known and assumed about the developmental influence of these neuropeptides and
      outlines the important unanswered questions and testable hypotheses. There is
      tremendous translational need to understand the functions of these neuropeptides
      in mammalian experience-dependent development of the social brain. The activity
      of oxytocin and vasopressin during development should inform our understanding of
      individual, sex, and species differences in social behavior later in life. 

PMID- 24863038
TI  - Adaptive changes in serotonin metabolism preserve normal behavior in mice with
      reduced TPH2 activity.
AB  - Polymorphisms in the TPH2 gene coding for the serotonin synthesizing enzyme in
      the brain are considered as risk factors associated with depression and anxiety
      in humans. However, whether a certain variation in the TPH2 gene leads to
      decreased brain serotonin production and development of psychological
      abnormalities remains unresolved. We generated a new mouse model, carrying one
      Tph2-null allele and one Tph21473G-allele, coding for a hypoactive form of the
      enzyme. We tested these mice along with C57BL/6 mice (Tph2C/C), congenic C57BL/6
      mice homozygous for the Tph21473G-allele (Tph2G/G), and heterozygous Tph2
      deficient mice (Tph2C/-) for anxiety- and depression-like behavior, and evaluated
      brain serotonin metabolism and 5-HT1AR signaling by high-performance liquid
      chromatography and quantitative autoradiography, respectively. Progressive
      reduction in TPH2 activity had no effect on emotional behavior, and only slightly
      affected brain serotonin levels. However, serotonin degradation rate was
      drastically decreased in mice with reduced TPH2 activity, thereby compensating
      for the lowered rate of serotonin production in these mice. In addition, the
      hypothermic response to the 5-HT1AR agonist, 8-OH-DPAT, was attenuated in mice
      with reduced serotonin production. In contrast, 5-HT1A autoreceptor density and G
      protein coupling were not changed in mice with gradual decrease in central
      serotonin. Taken together, these data suggest that in conditions of reduced
      serotonin production lowered serotonin degradation rate contributes to the
      maintenance of brain serotonin at levels sufficient for adequate behavior
      responses. These findings reveal that decreased TPH2 activity cannot be
      considered a reliable predisposition factor for impaired emotional behavior.

PMID- 24863033
TI  - Chronic treatment with novel brain-penetrating selective NOP receptor agonist MT
      7716 reduces alcohol drinking and seeking in the rat.
AB  - Since its discovery, the nociceptin/orphanin FQ (N/OFQ)-NOP receptor system has
      been extensively investigated as a promising target to treat alcoholism.
      Encouraging results obtained with the endogenous ligand N/OFQ stimulated research
      towards the development of novel brain-penetrating NOP receptor agonists with a
      pharmacological and toxicological profile compatible with clinical development.
      Here we describe the biochemical and alcohol-related behavioral effects of the
      novel NOP receptor agonist MT-7716. MT-7716 has high affinity for human NOP
      receptors expressed in HEK293 cells with a Ki value of 0.21 nM. MT-7716
      concentration-dependently stimulated GTPgamma(35)S binding with an EC50 value of
      0.30 nM and its efficacy was similar to N/OFQ, suggesting that MT7716 is a full
      agonist at NOP receptors. In the two bottle choice test MT-7716 (0, 0.3, 1, and 3
      mg/kg, bid) given orally for 14 days dose-dependently decreased voluntary alcohol
      intake in Marchigian Sardinian rats. The effect became gradually stronger
      following repeated administration, and was still significant 1 week after
      discontinuation of the drug. Oral naltrexone (30 mg/kg, bid) for 14 days also
      reduced ethanol intake; however, the effect decreased over the treatment period
      and rapidly disappeared when drug treatment was discontinued. MT-7716 is also
      effective for preventing reinstatement caused by both ethanol-associated
      environmental stimuli and stress. Finally, to investigate the effect of MT-7716
      on alcohol withdrawal symptoms, Wistar rats were withdrawn from a 7-day alcohol
      liquid diet. MT-7716 significantly attenuated somatic alcohol withdrawal
      symptoms. Together these findings indicate that MT-7716 is a promising candidate
      for alcoholism treatment remaining effective with chronic administration.

PMID- 24863037
TI  - The efficacy of three formulations of Lippia sidoides Cham. essential oil in the
      reduction of salivary Streptococcus mutans in children with caries: a randomized,
      double-blind, controlled study.
AB  - Essential oils of many plants have been previously tested in the treatment of
      oral diseases and other infections. This study was a randomized, double-blind, in
      parallel with an active control study, which aimed to evaluate the efficacy of
      three formulations of the Lippia sidoides Cham. essential oil (LSO) in the
      reduction of salivary Streptococcus mutans in children with caries. 81
      volunteers, aged 6-12 years, both genders, with caries, were recruited to
      participate in this study, and randomly assigned to either one of five different
      groups. Each group received topical treatment with either 1.4% LSO toothpaste,
      1.4% LSO gel, 0.8% LSO mouthwash, 1% chlorhexidine gel, or 0.12% chlorhexidine
      mouthwash. A 5-ml volume of each gel was placed inside disposable trays, and
      applied for 1 min, every 24h, for 5 consecutive days. The mouthwash groups used 5
      ml volume of a mouthwash inside disposable syringes. In the toothpaste group,
      children brushed their teeth for 1 min, once a day for 5 days. Saliva was
      collected before and after treatment. MS colonies were counted, isolated and
      confirmed through biochemical tests. Differences in MS levels measured in
      different days within the same treatment group was only verified with LSO
      toothpaste, chlorhexidine gel and chlorhexidine mouthwash. Comparison between
      groups of LSO mouthwash, toothpaste and gel showed that the toothpaste group
      expressed significantly lower MS levels than the mouthwash and gel groups at day
      30. Chlorhexidine significantly reduced MS levels after 5 days of treatment, but
      these levels returned to baseline in other periods of the study. LSO toothpaste
      reduced MS levels after 5 days of treatment, and MS levels remained low and did
      not return to baseline during subsequent analysis. Hence, LSO toothpaste
      demonstrated the most long-lasting MS reduction in saliva, whereas other LSO
      formulations did not effectively reduce MS levels in children with dental caries.

PMID- 24863039
TI  - New insights into mechanisms of opioid inhibitory effects on capsaicin-induced
      TRPV1 activity during painful diabetic neuropathy.
AB  - Painful diabetic neuropathy is a disease of the peripheral sensory neuron with
      impaired opioid responsiveness. Since MU-opioid receptor (MOR) activation can
      inhibit the transient receptor potential vanilloid 1 (TRPV1) activity in
      peripherally sensory neurons, this study investigated the mechanisms of impaired
      opioid inhibitory effects on capsaicin-induced TRPV1 activity in painful diabetic
      neuropathy. Intravenous injection of streptozotocin (STZ, 45 mg/kg) in Wistar
      rats led to a degeneration of insulin producing pancreatic beta-cells, elevated
      blood glucose, and mechanical hypersensitivity (allodynia). In these animals,
      local morphine's inhibitory effects on capsaicin-induced nocifensive behavior as
      well as on capsaicin-induced TRPV1 current in dorsal root ganglion cells were
      significantly impaired. These changes were associated with a loss in MOR but not
      TRPV1 in peripheral sensory neurons. Intrathecal delivery of nerve growth factor
      in diabetic animals normalized sensory neuron MOR and subsequently rescued
      morphine's inhibitory effects on capsaicin-induced TRPV1 activity in vivo and in
      vitro. These findings identify a loss in functional MOR on sensory neurons as a
      contributing factor for the impaired opioid inhibitory effects on capsaicin
      induced TRPV1 activity during advanced STZ-induced diabetes. Moreover, they
      support growing evidence of a distinct regulation of opioid responsiveness during
      various painful states of disease (e.g. arthritis, cancer, neuropathy) and may
      give novel therapeutic incentives. 

PMID- 24863040
TI  - Novel insights into the neurobiology underlying LRRK2-linked Parkinson's disease.
AB  - Mutations in LRRK2 (leucine-rich repeat kinase 2) are found associated with both
      sporadic and familial Parkinson's disease (PD). Pathogenic mutations are
      localized to the catalytic domains of LRRK2, including kinase and GTPase domains.
      Altered catalytic activity correlates with neurotoxicity, indicating that
      targeting those activities may provide clues as to novel therapeutic strategies
      for LRRK2-linked PD. However, the cellular readout of such altered catalytic
      activities remains largely unknown. Recent cell biological studies have started
      to highlight possible early cellular events which are altered in the presence of
      pathogenic LRRK2 and may ultimately lead to neuronal demise, and these studies
      link altered LRRK2 function to various abnormal endolysosomal vesicular
      trafficking events. This review examines our current knowledge of LRRK2
      neurobiology and how pathogenic mutations may lead to neurodegeneration in PD. 

PMID- 24863042
TI  - NMDA receptor antagonism potentiates the L-DOPA-induced extracellular dopamine
      release in the subthalamic nucleus of hemi-parkinson rats.
AB  - Long term treatment with L-3,4-dihydroxyphenylalanine (L-DOPA) is associated with
      several motor complications. Clinical improvement of this treatment is therefore
      needed. Lesions or high frequency stimulation of the hyperactive subthalamic
      nucleus (STN) in Parkinson's disease (PD), alleviate the motor symptoms and
      reduce dyskinesia, either directly and/or by allowing the reduction of the L-DOPA
      dose. N-methyl-D-aspartate (NMDA) receptor antagonists might have similar
      actions. However it remains elusive how the neurochemistry changes in the STN
      after a separate or combined administration of L-DOPA and a NMDA receptor
      antagonist. By means of in vivo microdialysis, the effect of L-DOPA and/or MK
      801, on the extracellular dopamine (DA) and glutamate (GLU) levels was
      investigated for the first time in the STN of sham and 6-hydroxydopamine-lesioned
      rats. The L-DOPA-induced DA increase in the STN was significantly higher in DA
      depleted rats compared to shams. MK 801 did not influence the L-DOPA-induced DA
      release in shams. However, MK 801 enhanced the L-DOPA-induced DA release in hemi
      parkinson rats. Interestingly, the extracellular STN GLU levels remained
      unchanged after nigral degeneration. Furthermore, administration of MK 801 alone
      or combined with L-DOPA did not alter the STN GLU levels in both sham and DA
      depleted rats. The present study does not support the hypothesis that DA-ergic
      degeneration influences the STN GLU levels neither that MK 801 alters the GLU
      levels in lesioned and non-lesioned rats. However, NMDA receptor antagonists
      could be used as a beneficial adjuvant treatment for PD by enhancing the
      therapeutic efficacy of l-DOPA at least in part in the STN.

PMID- 24863043
TI  - Induction of brain cytochrome P450 2E1 boosts the locomotor-stimulating effects
      of ethanol in mice.
AB  - In the central nervous system ethanol (EtOH) is metabolized into acetaldehyde by
      different enzymes. Brain catalase accounts for 60% of the total production of
      EtOH-derived acetaldehyde, whereas cerebral cytochrome P450 2E1 (CYP 2E1)
      produces 20% of this metabolite. Acetaldehyde formed by the activity of central
      catalase has been implicated in some of the neurobehavioral properties of EtOH,
      yet the contribution of CYP 2E1 to the pharmacological actions of this drug has
      not been investigated. Here we assessed the possible participation of CYP 2E1 in
      the behavioral effects of EtOH. Thus, we induced CYP 2E1 activity and expression
      by exposing mice to chronic acetone intake (1% v/v for 10 days) and examined its
      consequences on the stimulating and uncoordinating effects of EtOH (0-3.2 g/kg)
      injected intraperitoneally. Our data showed that 24 h after withdrawal of acetone
      brain expression and activity of CYP 2E1 was induced. Furthermore, the locomotion
      produced by EtOH was boosted over the same interval of time. Locomotor
      stimulation produced by amphetamine or tert-butanol was unchanged by previous
      treatment with acetone. EtOH-induced motor impairment as evaluated in a Rota-Rod
      apparatus was unaffected by the preceding exposure to acetone. These results
      indicate that cerebral CYP 2E1 activity could contribute to the locomotor
      stimulating effects of EtOH, and therefore we suggest that centrally produced
      acetaldehyde might be a possible mediator of some EtOH-induced pharmacological
      effects. 

PMID- 24863044
TI  - Overlap of food addiction and substance use disorders definitions: analysis of
      animal and human studies.
AB  - Food has both homeostatic and hedonic components, which makes it a potent natural
      reward. Food related reward could therefore promote an escalation of intake and
      trigger symptoms associated to withdrawal, suggesting a behavioral parallel with
      substance abuse. Animal and human theoretical models of food reward and addiction
      have emerged, raising further interrogations on the validity of a bond between
      Substance Use Disorders, as clinically categorized in the DSM 5, and food reward.
      These models propose that highly palatable food items, rich in sugar and/or fat,
      are overly stimulating to the brain's reward pathways. Moreover, studies have
      also investigated the possibility of causal link between food reward and the
      contemporary obesity epidemic, with obesity being potentiated and maintained due
      to this overwhelming food reward. Although natural rewards are a hot topic in the
      definition and categorization of Substance Use Disorders, proofs of concept and
      definite evidence are still inconclusive. This review focuses on available
      results from experimental studies in animal and human models exploring the
      concept of food addiction, in an effort to determine if it depicts a specific
      phenotype and if there is truly a neurobiological similarity between food
      addiction and Substance Use Disorders. It describes results from sugar, fat and
      sweet-fat bingeing in rodent models, and behavioral and neurobiological
      assessments in different human populations. Although pieces of behavioral and
      neurobiological evidence supporting a food addiction phenotype in animals and
      humans are interesting, it seems premature to conclude on its validity. 

PMID- 24863041
TI  - Age-related changes in nicotine response of cholinergic and non-cholinergic
      laterodorsal tegmental neurons: implications for the heightened adolescent
      susceptibility to nicotine addiction.
AB  - The younger an individual starts smoking, the greater the likelihood that
      addiction to nicotine will develop, suggesting that neurobiological responses
      vary across age to the addictive component of cigarettes. Cholinergic neurons of
      the laterodorsal tegmental nucleus (LDT) are importantly involved in the
      development of addiction, however, the effects of nicotine on LDT neuronal
      excitability across ontogeny are unknown. Nicotinic effects on LDT cells across
      different age groups were examined using calcium imaging and whole-cell patch
      clamping. Within the youngest age group (P7-P15), nicotine induced larger
      intracellular calcium transients and inward currents. Nicotine induced a greater
      number of excitatory synaptic currents in the youngest animals, whereas larger
      amplitude inhibitory synaptic events were induced in cells from the oldest
      animals (P15-P34). Nicotine increased neuronal firing of cholinergic cells to a
      greater degree in younger animals, possibly linked to development associated
      differences found in nicotinic effects on action potential shape and
      afterhyperpolarization. We conclude that in addition to age-associated
      alterations of several properties expected to affect resting cell excitability,
      parameters affecting cell excitability are altered by nicotine differentially
      across ontogeny. Taken together, our data suggest that nicotine induces a larger
      excitatory response in cholinergic LDT neurons from the youngest animals, which
      could result in a greater excitatory output from these cells to target regions
      involved in development of addiction. Such output would be expected to be
      promotive of addiction; therefore, ontogenetic differences in nicotine-mediated
      increases in the excitability of the LDT could contribute to the differential
      susceptibility to nicotine addiction seen across age. 

PMID- 24863045
TI  - Novel oxazolo-oxazole derivatives of FTY720 reduce endothelial cell permeability,
      immune cell chemotaxis and symptoms of experimental autoimmune encephalomyelitis
      in mice.
AB  - The immunomodulatory FTY720 (fingolimod) is presently approved for the treatment
      of relapsing-remitting multiple sclerosis. It is a prodrug that acts by
      modulating sphingosine 1-phosphate (S1P) receptor signaling. In this study, we
      have developed and characterized two novel oxazolo-oxazole derivatives of FTY720,
      ST-968 and the oxy analog ST-1071, which require no preceding activating
      phosphorylation, and proved to be active in intact cells and triggered S1P1 and
      S1P3, but not S1P2, receptor internalization as a result of receptor activation.
      Functionally, ST-968 and ST-1071 acted similar to FTY720 to abrogate S1P
      triggered chemotaxis of mouse splenocytes, mouse T cells and human U937 cells,
      and reduced TNFa- and LPS-stimulated endothelial cell permeability. The compounds
      also reduced TNFalpha-induced ICAM-1 and VCAM-1 mRNA expression, but restored
      TNFalpha-mediated downregulation of PECAM-1 mRNA expression. In an in vivo
      setting, the application of ST-968 or ST-1071 to mice resulted in a reduction of
      blood lymphocytes and significantly reduced the clinical symptoms of experimental
      autoimmune encephalomyelitis (EAE) in C57BL/6 mice comparable to FTY720 either by
      prophylactic or therapeutic treatment. In parallel to the reduced clinical
      symptoms, infiltration of immune cells in the brain was strongly reduced, and in
      isolated tissues of brain and spinal cord, the mRNA and protein expressions of
      ICAM-1 and VCAM-1, as well as of matrix metalloproteinase-9 were reduced by all
      compounds, whereas PECAM-1 and tissue inhibitor of metalloproteinase TIMP-1 were
      upregulated. In summary, the data suggest that these novel butterfly derivatives
      of FTY720 could have considerable implication for future therapies of multiple
      sclerosis and other autoimmune diseases. 

PMID- 24863047
TI  - Considerations regarding online methods for suicide-related research and suicide
      risk assessment.
AB  - Frequent advances in technology provide new and exciting opportunities for
      conducting suicide research and suicide risk assessments. However, to the
      authors' knowledge, best practices for using technology, specifically the
      Internet, to conduct research protocols involving suicide risk assessments have
      not been examined. In research contexts, the use of technology for research on
      suicidal behavior and suicide risk assessment can offer benefits relative to
      other forms of data collection. These advantages, which include increased
      validity, feasibility, and efficiency, as well as improvements in data collection
      and management, are presented. Considerations regarding the implementation of an
      online system for suicide risk assessment as well as limitations and future
      directions are discussed. 

PMID- 24863046
TI  - SSP-002392, a new 5-HT4 receptor agonist, dose-dependently reverses scopolamine
      induced learning and memory impairments in C57Bl/6 mice.
AB  - 5-HT4 receptors (5-HT4R) are suggested to affect learning and memory processes.
      Earlier studies have shown that animals treated with 5-HT4R agonists, often with
      limited selectivity, show improved learning and memory with retention memory
      often being assessed immediately after or within 24 h after the last training
      session. In this study, we characterized the effect of pre-training treatment
      with the selective 5-HT4R agonist SSP-002392 on memory acquisition and the
      associated long-term memory retrieval in animal models of impaired cognition. Pre
      training treatment with SSP-002392 (0.3 mg/kg, 1.5 mg/kg and 7.5 mg/kg p.o.) dose
      dependently inhibited the cognitive deficits induced by scopolamine (0.5 mg/kg
      s.c.) in two different behavioral tasks: passive avoidance and Morris water maze.
      In the Morris water maze, spatial learning was significantly improved after
      treatment with SSP-002392 translating in an accelerated and more efficient
      localization of the hidden platform compared to scopolamine-treated controls.
      Moreover, retention memory was assessed 24 h (passive avoidance) and 72 h (Morris
      water maze) after the last training session of cognitive-impaired animals and
      this was significantly improved in animals treated with SSP-002392 prior to the
      training sessions. Furthermore, the effects of SSP-002392 were comparable to
      galanthamine hydrobromide. We conclude that SSP-002392 has potential as a memory
      enhancing compound. 

PMID- 24863048
TI  - Evaluation of in vitro properties of predicted kinases that phosphorylate serine
      residues within nuclear localization signal 1 of high mobility group box 1.
AB  - Phosphorylation of high mobility group box 1 (HMGB1) is involved in the
      subcellular translocation of this protein and its subsequent secretion. Two
      nuclear localization signals (NLSs), NLS1 and NLS2, in this protein regulate its
      nucleocytoplasmic relocation, and phosphorylation of both NLSs strongly promotes
      HMGB1 mobilization. However, the phosphorylation properties of serine residues in
      NLS1 and the kinases involved are not well known. In the present study, we
      predicted kinases that phosphorylate serine residues in NLS1 and performed an in
      vitro kinase assay utilizing NLS1-derived phosphopeptides. Among the predicted
      kinases, protein kinase C phosphorylated Ser(46) of HMGB1-derived peptides, and a
      mutagenesis experiment confirmed that phosphorylation at this site could induce
      the translocation of the N-terminal region of NLS1-containing HMGB1 into the
      cytosol.

PMID- 24863049
TI  - Primary cilium and sonic hedgehog signaling during neural tube patterning: role
      of GPCRs and second messengers.
AB  - The ventral neural tube in vertebrates is patterned by a gradient of sonic
      hedgehog (Shh) secreted from the notochord and floor plate. Forward genetic
      screens first pointed to the role of the primary cilium in ventral neural tube
      patterning. Further research has shown that most components of the Shh pathway
      localize to or shuttle through the primary cilium. In the absence of Shh, the
      bifunctional Gli transcription factors are proteolytically processed into
      repressor forms in a protein kinase A (PKA)- and cilium-dependent manner. Recent
      work suggests that the orphan G-protein-coupled receptor (GPCR) Gpr161 localizes
      to cilia, and functions as a negative regulator of Shh signaling by determining
      Gli processing via cAMP signaling. The primary cilium also functions as a
      signaling compartment for calcium in the Shh pathway. A better understanding of
      the role of the cilium as a signaling compartment, and the interplay of second
      messenger systems that regulate PKA activation and Gli amplification during
      signaling is critical for deciphering the role of Shh during development,
      neuronal differentiation, and tumorigenesis.

PMID- 24863050
TI  - Patterns of postcranial ossification and sequence heterochrony in bats: life
      histories and developmental trade-offs.
AB  - The recently increased interest in studies on sequence heterochrony has uncovered
      developmental variation between species. However, how changes in developmental
      program are related to shifts in life-history parameters remains largely
      unsolved. Here we provide the most comprehensive data to date on postcranial
      ossification sequence of bats and compare them to various boreoeutherian mammals
      with different locomotive modes. Given that bats are equipped with an elongated
      manus, we expected to detect characteristic heterochronies particularly related
      to wing development. Although heterochronies related to wing development were
      confirmed as predicted, unexpected heterochronies regarding the pedal digits were
      also found. The timing of ossification onset of pedal phalanges is earlier than
      other mammals. Particularly, bats deviate from others in that pedal phalanges
      initiate ossification earlier than manual phalanges. It is known that the foot
      size of new born bats is close to that of adults, and that it takes several weeks
      to month until the wing is developed for flight. Given that the foot is required
      to be firm and stable enough at the time of birth to allow continued attachment
      to the mother and/or cave walls, we suggest that the accelerated development of
      the hind foot is linked to their unique life history. Since the forelimb is not
      mature enough for flight at birth and requires extended postnatal time to be
      large enough to be fully functional, we postulate that bats invest in earlier
      development of the hindlimb. We conclud that energy allocation trade-offs can
      play a significant role in shaping the evolution of development.

PMID- 24863051
TI  - Visible-light-induced electron transport from small to large nanoparticles in
      bimodal gold nanoparticle-loaded titanium(IV) oxide.
AB  - A key to realizing the sustainable society is to develop highly active
      photocatalysts for selective organic synthesis effectively using sunlight as the
      energy source. Recently, metal-oxide-supported gold nanoparticles (NPs) have
      emerged as a new type of visible-light photocatalysts driven by the excitation of
      localized surface plasmon resonance of Au NPs. Here we show that visible-light
      irradiation (lambda>430 nm) of TiO2 -supported Au NPs with a bimodal size
      distribution (BM-Au/TiO2 ) gives rise to the long-range (>40 nm) electron
      transport from about 14 small (ca. 2 nm) Au NPs to one large (ca. 9 nm) Au NP
      through the conduction band of TiO2 . As a result of the enhancement of charge
      separation, BM-Au/TiO2 exhibits a high level of visible-light activity for the
      one-step synthesis of azobenzenes from nitrobenzenes at 25  degrees C with a
      yield greater than 95 % and a selectivity greater than 99 %, whereas unimodal
      Au/TiO2 (UM-Au/TiO2 ) is photocatalytically inactive. 

PMID- 24863052
TI  - Biocatalytic synthesis of maltodextrin-based acrylates from starch and alpha
      cyclodextrin.
AB  - Novel 2-(beta-maltooligooxy)-ethyl (meth)acrylate monomers are successfully
      synthesized by CGTase from Bacillus macerans catalyzed coupling of 2-(beta
      glucosyloxy)-ethyl acrylate and methacrylate with alpha-cyclodextrin or starch.
      HPLC-UV analysis shows that the CGTase catalyzed reaction yields 2-(beta
      maltooligooxy)-ethyl acrylates with 1 to 15 glucopyranosyl units. (1) H NMR
      spectroscopy reveals that the beta-linkage in the acceptor molecule is preserved
      during the CGTase catalyzed coupling reaction, whereas the newly introduced
      glucose units are attached by alpha-(1,4)-glycosidic linkages. The synthesized 2
      (beta-maltooligooxy)-ethyl acrylate monomers are successfully polymerized by
      aqueous free radical polymerization to yield the comb-shaped glycopolymer poly(2
      (beta-maltooligooxy)-ethyl acrylate). 

PMID- 24863053
TI  - Knowing how to look predicts the ability to draw realistically.
AB  - Some young children are able to create stunningly realistic drawings resembling
      those of adult artists. What perceptual abilities underlie this talent? This
      study examined two candidate skills on which adult artists excel: the ability to
      segment a complex form mentally (measured by the Block Design Task) and the
      ability to see hidden forms (measured by the Group Embedded Figures Test). Sixty
      seven 6- to 13-year-olds with a wide range of drawing abilities completed these
      tasks as well as an IQ test and an observational drawing task. While children who
      scored high on drawing realism outperformed those who scored low in drawing
      realism on both perceptual tasks, only detection of embedded figures predicted
      drawing realism. This occurred independently of age, gender, years of training,
      and verbal and non-verbal IQ. There are certainly many contributors to this
      complex ability, but one component appears to be the tendency to see things more
      as they really are and thereby recognize the continuous contour of an object
      despite interference from other overlapping objects. 

PMID- 24863054
TI  - Outcomes of lead revision for myocardial perforation after cardiac implantable
      electronic device placement.
AB  - INTRODUCTION: Cardiac perforation is an infrequent but potentially life
      threatening complication associated with placement of a cardiac implantable
      electronic device (CIED). The objective of this study was to determine the
      outcomes of percutaneous lead revision in patients who had lead perforation of
      the myocardium after CIED placement. METHODS AND RESULTS: We reviewed records of
      1,458 patients who underwent CIED lead extraction or repositioning. Of these, 31
      (2.1%) had the procedure performed for lead perforation as a complication of CIED
      placement. Demographic, clinical, and follow-up characteristics of the patients
      were analyzed. Mean (SD) patient age was 65 (23) years. Cardiac perforation was
      detected within 24 hours after implantation in 9 patients, within 1 month in 17,
      and greater than 1 month in 5. Pericardiocentesis was performed with a pigtail
      drainage catheter in place before the lead revision in 17 patients (55%) who had
      pericardial effusion, with or without hemodynamic compromise. All culprit leads
      were successfully managed with percutaneous lead removal (n = 3 [10%]), new lead
      placement (n = 12 [38%]), or lead repositioning (n = 16 [52%]). Of the 17
      patients with pericardiocentesis before the reoperation, none had tamponade
      develop; in contrast, 3 of the remaining 14 patients had tamponade develop and
      required urgent pericardiocentesis. All patients survived without requiring open
      chest surgery. CONCLUSION: Percutaneous removal or repositioning of the
      perforating lead is feasible and appears effective. Placement of a prophylactic
      pericardial drain catheter may reduce the incidence of urgent pericardiocentesis
      during or after a procedure.

PMID- 24863055
TI  - Shared decision making in transplantation: how patients see their role in the
      decision process of accepting a donor liver.
AB  - At the time of the organ offer for transplantation, donor-related risks such as
      disease transmission and graft failure are weighed against the patient's risk of
      remaining on the waiting list. The patient's commonly inactive role in decision
      making and the timing and extent of donor-specific risk information have been
      discussed in the medical literature. This is the first study revealing the
      opinions of liver patients on these issues. Forty patients listed for liver
      transplantation and 179 liver transplant patients participated in an anonymous
      questionnaire-based survey. The majority of the patients wanted to be informed
      about donor-related risks (59.8%-74.8%). The preferred timing for being informed
      about donor-related risks was the time of the organ offer for 53.3% of the
      patients. Among these patients, 79.8% wished to be involved in making the
      decision to accept or not accept a liver for transplantation, 10.6% wished to
      make the final decision alone, and only 9.6% did not want to be involved in the
      decision-making process. Implementing this knowledge through the standardization
      of the content, the manner of transfer, and the amount of information that we
      provide to our patients will improve opportunities for shared decision making at
      different time points during the transplant allocation process. This will enable
      us to provide the same opportunities and care to every patient on the waiting
      list.

PMID- 24863056
TI  - The role of sterols in the lipid vesicle response induced by the pore-forming
      agent nystatin.
AB  - The influences of ergosterol and cholesterol on the activity of the nystatin were
      investigated experimentally in a POPC model membrane as well as theoretically.
      The behavior of giant unilamellar vesicles (GUVs) under osmotic stress due to the
      formation of transmembrane pores was observed on single vesicles at different
      nystatin concentrations using phase-contrast microscopy. A significant shift of
      the typical vesicle behavior, i.e., morphological alterations, membrane bursts,
      slow vesicle ruptures and explosions, towards lower nystatin concentrations was
      detected in the ergosterol-containing vesicles and a slight shift towards higher
      nystatin concentrations was detected in the cholesterol-containing membranes. In
      addition, the nystatin activity was shown to be significantly affected by the
      ergosterol membrane's molar fraction in a non-proportional manner. The observed
      tension-pore behavior was interpreted using a theoretical model based on the
      osmotic phenomena induced by the occurrence of size-selective nystatin pores. The
      number of nystatin pores for different vesicle behavior was theoretically
      determined and the role of the different mechanical characteristics of the
      membrane, i.e., the membrane's expansivity and bending moduli, the line tension
      and the lysis tension, in the tension-pore formation process was quantified. The
      sterol-induced changes could not be explained adequately on the basis of the
      different mechanical characteristics, and were therefore interpreted mainly by
      the direct influences of the membrane sterols on the membrane binding, the
      partition and the pore-formation process of nystatin. 

PMID- 24863058
TI  - Targeting kidney CLC-K channels: pharmacological profile in a human cell line
      versus Xenopus oocytes.
AB  - CLC-K chloride channels play a crucial role in kidney physiology and genetic
      mutations, affecting their function are responsible for severe renal salt loss in
      humans. Thus, compounds that selectively bind to CLC-Ka and/or CLC-Kb channels
      and modulate their activity may have a significant therapeutic potential. Here,
      we compare the biophysical and pharmacological behaviors of human CLC-K channels
      expressed either in HEK293 cells or in Xenopus oocytes and we show that CLC-K
      channel properties are greatly influenced by the biochemical environment
      surrounding the channels. Indeed, in HEK293 cells the potentiating effect of
      niflumic acid (NFA) on CLC-Ka/barttin and CLC-Kb/barttin channels seems to be
      absent while the blocking efficacy of niflumic acid and benzofuran derivatives
      observed in oocytes is preserved. The NFA block does not seem to involve the
      accessory subunit barttin on CLC-K1 channels. In addition, the sensitivity of CLC
      Ks to external Ca(2+) is reduced in HEK293 cells. Based on our findings, we
      propose that mammalian cell lines are a suitable expression system for the
      pharmacological profiling of CLC-Ks. 

PMID- 24863057
TI  - Glutamate provides a key structural contact between reticulon-4 (Nogo-66) and
      phosphocholine.
AB  - Human reticulon 4 (RTN-4) has been identified as the neurite outgrowth inhibitor
      (Nogo). This protein contains a span of 66 amino acids (Nogo-66) flanked by two
      membrane helices at the C-terminus. We previously determined the NMR structure of
      Nogo-66 in a native-like environment and defined the regions of Nogo-66 expected
      to be membrane embedded. We hypothesize that aromatic groups and a negative
      charge hyperconserved among RTNs (Glu26) drive the remarkably strong association
      of Nogo-66 with a phosphocholine surface. Glu26 is an isolated charge with no
      counterion provided by nearby protein groups. We modeled the docking of
      dodecylphosphocholine (DPC) with Nogo-66 and found that a lipid choline group
      could form a stable salt bridge with Glu26 and serve as a membrane anchor point.
      To test the role of the Glu26 anion in binding choline, we mutated this residue
      to alanine and assessed the structural consequences, the association with lipid
      and the affinity for the Nogo receptor. In an aqueous environment, Nogo-66
      Glu26Ala is more helical than WT and binds the Nogo receptor with higher
      affinity. Thus, we can conclude that in the absence of a neutralizing positive
      charge provided by lipid, the glutamate anion is destabilizing to the Nogo-66
      fold. Although the Nogo-66 Glu26Ala free energy of transfer from water into lipid
      is similar to that of WT, NMR data reveal a dramatic loss of tertiary structure
      for the mutant in DPC micelles. These data show that Glu26 has a key role in
      defining the structure of Nogo-66 on a phosphocholine surface. This article is
      part of a special issue entitled: Interfacially Active Peptides and Proteins.
      Guest Editors: William C. Wimley and Kalina Hristova. 

PMID- 24863059
TI  - A DEAD-box RNA helicase produces two forms of transcript that differentially
      respond to cold stress in a cryophyte (Chorispora bungeana).
AB  - MAIN CONCLUSION: This work demonstrated that a cold-induced DEAD-box RNA
      helicase, CbDRH, is also post-transcriptionally regulated upon cold stress, and
      it interacts with a cold-responsive, glycine-rich, RNA-binding protein, CbGRP.
      Chorispora bungeana (C. bungeana) is a representative alpine subnival plant
      species that shows strong tolerance to multiple abiotic stresses, especially cold
      stress. DEAD-box RNA helicases are implicated in almost all RNA metabolic
      processes and participate in multiple abiotic stress responses. Here, we
      characterized a cold-induced DEAD-box RNA helicase gene from C. bungeana. We
      cloned the full-length cDNA of the gene by RACE and called it C. bungeana DEAD
      box RNA Helicase (CbDRH). Structurally, CbDRH possesses all nine conserved motifs
      characteristic of DEAD-box protein family members in its central region, and the
      N- and C- terminal extensions both harbor a glycine-rich region containing
      several RGG-box motifs. The CbDRH gene produces two forms of transcripts, CbDRH.2
      and CbDRH.1, by alternative splicing. CbDRH.2 comes from the complete excision of
      all the nine introns, while CbDRH.1 results from the use of an alternative 5'
      splice site in the eighth intron, retaining part of the intron (the first 260 bp)
      with an early stop codon. Semi-quantitative RT-PCR analysis showed that CbDRH.2,
      but not CbDRH.1, is up-regulated by cold stress. However, the abundance of
      CbDRH.1 transcript can be elevated by cycloheximide (an inhibitor of nonsense
      mediated decay) treatment, indicating that CbDRH.1 is targeted to nonsense
      mediated decay (NMD). A subcellular localization analysis showed that CbDRH.2
      protein is located in the nuclei. Further investigation suggested that CbDRH.2
      can interact with a cold-responsive, glycine-rich, RNA-binding protein, CbGRP
      (Chorispora bungeana glycine-rich, RNA-binding protein). These data suggest that
      the cold-induced CbDRH is also post-transcriptionally regulated under cold stress
      and that CbDRH.2 may function together with the glycine-rich, RNA-binding
      protein, CbGRP, in the cold stress response.

PMID- 24863060
TI  - Characterization of a plant (rice) translin and its comparative analysis with
      human translin.
AB  - MAIN CONCLUSION: For the first time, a plant (rice) translin was characterized.
      The rice translin protein, which was octameric in native state, bound efficiently
      to single-stranded DNA and RNA. Translin, a DNA-/RNA-binding protein, is
      expressed in brain, testis and in certain malignancies. It is involved in
      chromosomal translocation, mRNA metabolism, transcriptional regulation and
      telomere protection. Studies from human, mice, drosophila and yeast have revealed
      that it forms an octameric ring, which is important for its function. In spite of
      the absence of neuronal functions and cancer processes, translin is present in
      plant systems, but information on plant translin is lacking. Here we report the
      characterization of a plant (rice) translin. Translin cDNA from O. sativa was
      cloned into an expression vector; protein was over-expressed in E. coli and
      subsequently purified to homogeneity. Circular dichroism and homology-based
      modeling showed that the rice translin protein was similar to the other translin
      proteins. Native PAGE and gel-filtration analyses showed rice translin to form an
      octamer and this octameric assembly was independent of disulphide bonds. Rice
      translin bound to single-stranded DNA sequences like human translin, but not to
      the double-stranded DNA. Rice translin bound more efficiently to linear DNA (with
      staggered ends) than open or closed circular DNA. Rice translin also bound to
      RNA, like its human counterpart. Rice translin displays all the characteristic
      properties of the translin group of proteins and does indeed qualify as a
      bonafide "translin" protein. To our knowledge, this is the first report wherein
      the translin protein from a plant source has been functionally characterized.
      Understanding the translin biology from plant systems will give the new insights
      into its functional role during plant development.

PMID- 24863061
TI  - The impact of locoregional recurrences and distant metastases on the survival of
      patients with papillary thyroid carcinoma.
AB  - OBJECTIVE: Some patients with papillary thyroid carcinoma (PTC) would suffer from
      locoregional recurrences or distant metastases. This study was aimed to elucidate
      the impacts of locoregional recurrences and distant metastases on these patients'
      survival. DESIGN: Retrospective hospital-based cohort study. POPULATION: Data
      were collected from 1636 subjects with PTC at National Taiwan University Hospital
      between 1985 and 2007. MEASUREMENTS: Overall and disease-specific survival curves
      were estimated by the Kaplan-Meier method. Time-independent and time-dependent
      prognostic factors were included simultaneously in multivariate analyses using
      Cox models. RESULTS: Overall survival (OS) rates at 10- and 20-years were 90% and
      76%, respectively. The 10- and 20-year disease-specific survival (DSS) rates were
      95% and 90%, respectively. Our multivariate analyses identified that older age,
      distant metastases (hazard ratio, HR: 6.69, 95% CI: 4.40-10.18), locoregional
      recurrences (HR: 1.88, 95% CI: 1.22-2.89), lymph node metastases, massive
      extrathyroid extension, male gender and larger tumour size (>4 cm) were
      significantly associated with poorer OS. Older age, distant metastases (HR:
      15.03, 95% CI: 8.31-27.21), locoregional recurrences (HR: 3.63, 95% CI: 2.03
      6.51), massive extrathyroid extension, male gender and larger tumour size (>4 cm)
      were independently related to worse DSS. The performance of high-dose (131) I
      ablation had a protective effect on OS and DSS. CONCLUSION: The locoregional
      recurrences had a moderately harmful impact on OS and DSS, but age and distant
      metastases were the major decisive factors for OS and DSS. High-dose (131) I
      ablation had a protective role. However, lymph node dissection did not alter the
      prognosis whenever lymph node metastases only influenced OS.

PMID- 24863062
TI  - Counter-regulation of T cell effector function by differentially activated p38.
AB  - Unlike the MAP kinase (MAPK) cascade that phosphorylates p38 on the activation
      loop, T cell receptor (TCR) signaling results in phosphorylation on Tyr-323
      (pY323, alternative pathway). Using mice expressing p38alpha and p38beta with
      Y323F substitutions, we show that alternatively but not MAPK cascade-activated
      p38 up-regulates the transcription factors NFATc1 and IRF4, which are required
      for proliferation and cytokine production. Conversely, activation of p38 with UV
      or osmotic shock mitigated TCR-mediated activation by phosphorylation and
      cytoplasmic retention of NFATc1. Notably, UVB treatment of human psoriatic
      lesions reduced skin-infiltrating p38 pY323(+) T cell IRF4 and IL-17 production.
      Thus, distinct mechanisms of p38 activation converge on NFATc1 with opposing
      effects on T cell immunity, which may underlie the beneficial effect of
      phototherapy on psoriasis. 

PMID- 24863063
TI  - Imatinib inhibits VEGF-independent angiogenesis by targeting neuropilin 1
      dependent ABL1 activation in endothelial cells.
AB  - To enable new blood vessel growth, endothelial cells (ECs) express neuropilin 1
      (NRP1), and NRP1 associates with the receptor tyrosine kinase VEGFR2 after
      binding the vascular endothelial growth factor A (VEGF) to enhance
      arteriogenesis. We report that NRP1 contributes to angiogenesis through a novel
      mechanism. In human and mouse ECs, the integrin ligand fibronectin (FN)
      stimulated actin remodeling and phosphorylation of the focal adhesion component
      paxillin (PXN) in a VEGF/VEGFR2-independent but NRP1-dependent manner. NRP1
      formed a complex with ABL1 that was responsible for FN-dependent PXN activation
      and actin remodeling. This complex promoted EC motility in vitro and during
      angiogenesis on FN substrates in vivo. Accordingly, both physiological and
      pathological angiogenesis in the retina were inhibited by treatment with
      Imatinib, a small molecule inhibitor of ABL1 which is widely used to prevent the
      proliferation of tumor cells that express BCR-ABL fusion proteins. The finding
      that NRP1 regulates angiogenesis in a VEGF- and VEGFR2-independent fashion via
      ABL1 suggests that ABL1 inhibition provides a novel opportunity for anti
      angiogenic therapy to complement VEGF or VEGFR2 blockade in eye disease or solid
      tumor growth. 

PMID- 24863064
TI  - Fate mapping reveals origin and dynamics of lymph node follicular dendritic
      cells.
AB  - Follicular dendritic cells (FDCs) regulate B cell function and development of
      high affinity antibody responses but little is known about their biology. FDCs
      associate in intricate cellular networks within secondary lymphoid organs. In
      vitro and ex vivo methods, therefore, allow only limited understanding of the
      genuine immunobiology of FDCs in their native habitat. Herein, we used various
      multicolor fate mapping systems to investigate the ontogeny and dynamics of lymph
      node (LN) FDCs in situ. We show that LN FDC networks arise from the clonal
      expansion and differentiation of marginal reticular cells (MRCs), a population of
      lymphoid stromal cells lining the LN subcapsular sinus. We further demonstrate
      that during an immune response, FDCs accumulate in germinal centers and that
      neither the recruitment of circulating progenitors nor the division of local
      mature FDCs significantly contributes to this accumulation. Rather, we provide
      evidence that newly generated FDCs also arise from the proliferation and
      differentiation of MRCs, thus unraveling a critical function of this poorly
      defined stromal cell population. 

PMID- 24863066
TI  - Vagus nerve controls resolution and pro-resolving mediators of inflammation.
AB  - Resolution of inflammation is now recognized as a biosynthetically active process
      involving pro-resolving mediators. Here, we show in zymosan-initiated peritoneal
      inflammation that the vagus nerve regulates local expression of netrin-1, an
      axonal guidance molecule that activates resolution, and that vagotomy reduced
      local pro-resolving mediators, thereby delaying resolution. In netrin-1(+/-)
      mice, resolvin D1 (RvD1) was less effective in reducing neutrophil influx
      promoting resolution of peritonitis compared with Ntn1(+/+). Netrin-1 shortened
      the resolution interval, decreasing exudate neutrophils, reducing proinflammatory
      mediators, and stimulating the production of resolvins, protectins, and lipoxins.
      Human monocytes incubated with netrin-1 produced proresolving mediators,
      including resolvins and lipoxins. Netrin-1 and RvD1 displayed bidirectional
      activation in that they stimulated each other's expression and enhanced
      efferocytosis. These results indicate that the vagus nerve regulates both netrin
      1 and pro-resolving lipid mediators, which act in a bidirectional fashion to
      stimulate resolution, and provide evidence for a novel mechanism for local
      neuronal control of resolution. 

PMID- 24863065
TI  - A negative feedback loop mediated by the Bcl6-cullin 3 complex limits Tfh cell
      differentiation.
AB  - Induction of Bcl6 (B cell lymphoma 6) is essential for T follicular helper (Tfh)
      cell differentiation of antigen-stimulated CD4(+) T cells. Intriguingly, we found
      that Bcl6 was also highly and transiently expressed during the CD4(+)CD8(+)
      (double positive [DP]) stage of T cell development, in association with the E3
      ligase cullin 3 (Cul3), a novel binding partner of Bcl6 which ubiquitinates
      histone proteins. DP stage-specific deletion of the E3 ligase Cul3, or of Bcl6,
      induced the derepression of the Bcl6 target genes Batf (basic leucine zipper
      transcription factor, ATF-like) and Bcl6, in part through epigenetic
      modifications of CD4(+) single-positive thymocytes. Although they maintained an
      apparently normal phenotype after emigration, they expressed increased amounts of
      Batf and Bcl6 at basal state and produced explosive and prolonged Tfh responses
      upon subsequent antigen encounter. Ablation of Cul3 in mature CD4(+) splenocytes
      also resulted in dramatically exaggerated Tfh responses. Thus, although previous
      studies have emphasized the essential role of Bcl6 in inducing Tfh responses, our
      findings reveal that Bcl6-Cul3 complexes also provide essential negative feedback
      regulation during both thymocyte development and T cell activation to restrain
      excessive Tfh responses. 

PMID- 24863067
TI  - Regulation of mammalian siderophore 2,5-DHBA in the innate immune response to
      infection.
AB  - Competition for iron influences host-pathogen interactions. Pathogens secrete
      small iron-binding moieties, siderophores, to acquire host iron. In response, the
      host secretes siderophore-binding proteins, such as lipocalin 24p3, which limit
      siderophore-mediated iron import into bacteria. Mammals produce 2,5-dihydroxy
      benzoic acid, a compound that resembles a bacterial siderophore. Our data suggest
      that bacteria use both mammalian and bacterial siderophores. In support of this
      idea, supplementation with mammalian siderophore enhances bacterial growth in
      vitro. In addition, mice lacking the mammalian siderophore resist E. coli
      infection. Finally, we show that the host responds to infection by suppressing
      siderophore synthesis while up-regulating lipocalin 24p3 expression via TLR
      signaling. Thus, reciprocal regulation of 24p3 and mammalian siderophore is a
      protective mechanism limiting microbial access to iron. 

PMID- 24863070
TI  - Regenerative healing, scar-free healing and scar formation across the species:
      current concepts and future perspectives.
AB  - All species have evolved mechanisms of repair to restore tissue function
      following injury. Skin scarring is an inevitable and permanent endpoint for many
      postnatal organisms except for non-amniote vertebrates such as amphibians, which
      are capable of tissue regeneration. Furthermore, mammalian foetuses through mid
      gestation are capable of rapid wound repair in the absence of scar formation.
      Notably, excessive cutaneous scar formation, such as hypertrophic and keloid
      scars, is a species limited clinical entity as it occurs only in humans, although
      wounds on the distal limbs of horses are also prone to heal with
      fibroproliferative pathology known as equine exuberant granulation tissue.
      Currently, there are no reliable treatment options to eradicate or prevent
      scarring in humans and vertebrates. The limited number of vertebrate models for
      either hypertrophic or keloid scarring has been an impediment to mechanistic
      studies of these diseases and the development of therapies. In this viewpoint
      essay, we highlight the current concepts of regenerative, scar-free and scar
      forming healing compared across a number of species and speculate on areas for
      future research. Furthermore, in-depth investigative research into the mechanisms
      of scarless repair may allow for the development of improved animal models and
      novel targets for scar prevention. As the ability to heal in both a scarless
      manner and propensity for healing with excessive scar formation is highly species
      dependent, understanding similarities and differences in healing across species
      as it relates to the regenerative process may hold the key to improve scarring
      and guide translational wound-healing studies. 

PMID- 24863069
TI  - Long-term outcomes after fertility-sparing laparoscopic radical trachelectomy in
      young women with early-stage cervical cancer: an Asan Gynecologic Cancer Group
      (AGCG) study.
AB  - OBJECTIVES: To evaluate the long-term outcomes and risk factors for recurrence
      after fertility-sparing laparoscopic radical trachelectomy (LRT) in young women
      with early-stage cervical cancer. METHODS: Eighty-eight consecutive patients from
      four tertiary cancer centers in Korea who had attempted fertility-sparing LRT for
      early-stage cervical cancer were included in this study. RESULTS: Seventy-nine
      patients completed LRT. The mean age and tumor size were 31 years (range, 20-40
      years) and 1.8 cm (range, 0.4-7 cm), respectively. Twenty-nine patients had a
      tumor size greater than 2 cm, 22 had deep stromal invasion greater than 50%, and
      twelve had lymphovascular space invasion. After a median follow-up time of 44
      months (range, 3-105 months), nine patients had recurrence and one had died of
      disease. A tumor size greater than 2 cm (P = 0.039) and a depth of stromal
      invasion greater than 50% (P = 0.016) were significant risk factors for
      recurrence. CONCLUSIONS: This is the largest series on fertility-sparing LRT in
      young women with early cervical cancer. LRT is a feasible and safe fertility
      sparing alternative to radical hysterectomy in these women. A tumor size greater
      than 2 cm and a depth of stromal invasion greater than 50% were risk factors for
      recurrence.

PMID- 24863068
TI  - B lymphocytes undergo TLR2-dependent apoptosis upon Shigella infection.
AB  - Antibody-mediated immunity to Shigella, the causative agent of bacillary
      dysentery, requires several episodes of infection to get primed and is short
      lasting, suggesting that the B cell response is functionally impaired. We show
      that upon ex vivo infection of human colonic tissue, invasive S. flexneri
      interacts with and occasionally invades B lymphocytes. The induction of a type
      three secretion apparatus (T3SA)-dependent B cell death is observed in the human
      CL-01 B cell line in vitro, as well as in mouse B lymphocytes in vivo. In
      addition to cell death occurring in Shigella-invaded CL-01 B lymphocytes, we
      provide evidence that the T3SA needle tip protein IpaD can induce cell death in
      noninvaded cells. IpaD binds to and induces B cell apoptosis via TLR2, a
      signaling receptor thus far considered to result in activation of B lymphocytes.
      The presence of bacterial co-signals is required to sensitize B cells to
      apoptosis and to up-regulate tlr2, thus enhancing IpaD binding. Apoptotic B
      lymphocytes in contact with Shigella-IpaD are detected in rectal biopsies of
      infected individuals. This study therefore adds direct B lymphocyte targeting to
      the diversity of mechanisms used by Shigella to dampen the host immune response. 

PMID- 24863071
TI  - Reflections on the role of nursing in primary care to transmit their knowledge of
      the principles of self-care in cases of heart failure.

PMID- 24863072
TI  - Heart failure patients' experiences of a self-management peer support program: a
      qualitative study.
AB  - OBJECTIVES: Explore the experiences of patients with heart failure in a self
      management support program to inform the development of future interventions that
      support and motivate patients to engage in self-management. BACKGROUND: Peer
      support programs have led to improved outcomes among patients with other chronic
      conditions and may result in similar improvements for heart failure patients.
      Yet, among patients recently hospitalized for heart failure, over half had no or
      minimal engagement with a reciprocal peer support program. METHODS: Qualitative
      semi-structured interviews with a purposive sample of 28 patients (mean age 72;
      71% Female; 21% African-American; 75% Caucasian) with different levels and types
      of engagement in a heart failure self-management support program. RESULTS: Key
      themes that emerged included the importance of heart failure specific-social
      support, sharing information, comparing self to others, depression, and
      functional status. CONCLUSIONS: Useful services for heart failure patients
      provide comfort, restore confidence, and offer practical solutions.

PMID- 24863073
TI  - Fatal rupture of aortic root abscess following native aortic valve enterococcal
      endocarditis.
AB  - We describe the case of a 66-year-old male, who was referred to our cardiology
      department with suspected endocarditis, following an enterococcal bacteremia.
      Transesophageal echocardiography showed vegetations on a native trileaflet aortic
      valve. Having been prescribed intravenous amoxicillin and gentamicin, to which he
      initially responded, the patient became increasingly breathless during the third
      week of treatment. Although lung fields were clear and there were no changes to a
      pre-existing heart murmur on physical examination, transthoracic echocardiography
      and Doppler color flow imaging revealed that an aortic root abscess had ruptured
      and formed a left-to-right shunt. The patient was transferred to a specialist
      cardiac center, but was unsuitable for major surgery and died a week later. We
      discuss this rare and devastating complication of infective endocarditis. 

PMID- 24863077
TI  - Current status of lower-extremity revascularization.

PMID- 24863079
TI  - Interleukin-6 blockade improves autonomic dysfunction in rheumatoid arthritis.
AB  - Autonomic nervous system (ANS) involvement in rheumatoid arthritis (RA) is well
      recognised and contributes to arrhythmia and sudden death. However, there is no
      study documented the therapeutic efficacy on autonomic neuropathy (AN) in RA.
      This is the first reported observation of improvement in AN with interleukin-6
      (IL-6) blockade with tocilizumab in RA. We report a case of 61-year old female
      with seropositive RA with severe disease activity, investigated for autonomic
      neuropathy. A battery of non invasive tests was used for accurate assessment of
      AN function based on assessment of peripheral sympathetic autonomic function and
      cardiovascular reflex tests. Tocilizumab 8 mg/kg intravenous infusion at weeks 0,
      4 and 8 was added to her treatment regimen. Cardiovascular autonomic function
      tests at baseline showed marked abnormalities of parasympathetic cardiovascular
      reflexes. After the first dose of tocilizumab there was a rapid improvement with
      normalization of parasympathetic autonomic activity with subsequent doses. IL-6
      blockade with tocilizumab seems to have the potential to improve the vagus nerve
      mediated parasympathetic neuropathy and hence has the potential to restore
      cholinergic anti-inflammatory pathway.

PMID- 24863078
TI  - Influence of hyperhomocysteinemia on left ventricular diastolic function in
      Chinese patients with hypertension.
AB  - OBJECTIVE: The aim of this study was to assess the effect of plasma homocysteine
      (Hcy) on left ventricular (LV) diastolic function in Chinese patients with
      essential hypertension. PATIENTS AND METHODS: A total of 74 patients with
      hypertension were enrolled in the present study and were divided into two groups
      according to the plasma levels of Hcy: high levels of Hcy (Hhcy) group (n = 37)
      and control group (n = 37) with normal levels of homocysteine. The study
      participants consisted of 37 hypertensive patients with Hhcy and 37 hypertensive
      patients without Hhcy. Transthoracic Doppler echocardiography was performed to
      assess the LV diastolic function of the patients. RESULTS: The plasma level of
      Hcy was directly related to LV diastolic echocardiographic parameters in patients
      with hypertension whereby the ratio E/e' was higher (12.7 +/- 2.64 vs. 8.98 +/-
      1.55, p < 0.01), e'/a' was lower (0.59 +/- 0.13 vs. 0.83 +/- 0.20, p < 0.01), and
      the left atrial (LA) diameter was longer (43.4 +/- 3.6 mm vs. 37.6 +/- 5.0 mm, p
      < 0.01) in the Hhcy group than in the control group. CONCLUSION: The LV diastolic
      function was significantly deteriorated in Chinese hypertensive patients with
      Hhcy and there were significant correlations between LV diastolic function
      indices and Hcy levels.

PMID- 24863080
TI  - Surface and zeta-potentials of silver halide single crystals: pH-dependence in
      comparison to particle systems.
AB  - We have carried out surface and zeta-potential measurements on AgCl and AgBr
      single crystals. As for particle systems we find that, surprisingly and
      previously unnoted, the zeta-potential exhibits pH-dependence, while the surface
      potential does not. A possible interpretation of these observations is the
      involvement of water ions in the interfacial equilibria and in particular,
      stronger affinity of the hydroxide ion compared to the proton. The pH-dependence
      of the zeta-potential can be suppressed at sufficiently high silver
      concentrations, which agrees with previous measurements in particle systems where
      no pH-dependence was found at high halide ion concentrations. The results suggest
      a subtle interplay between the surface potential determining the halide and
      silver ion concentrations, and the water ions. Whenever the charge due to the
      halide and silver ions is sufficiently high, the influence of the
      proton/hydroxide ion on the zeta-potential vanishes. This might be related to the
      water structuring at the relevant interfaces which should be strongly affected by
      the surface potential. Another interesting observation is accentuation of the
      assumed water ion effect on the zeta-potential at the flat single crystal
      surfaces compared to the corresponding silver halide colloids. Previous generic
      MD simulations have indeed predicted that hydroxide ion adsorption is accentuated
      on flat/rigid surfaces. A thermodynamic model for AgI single crystals was
      developed to describe the combined effects of iodide, silver and water ions,
      based on two independently previously published models for AgI (that only
      consider constituent and background electrolyte ions) and inert surfaces (that
      only consider water and background electrolyte ions). The combined model
      correctly predicts all the experimentally observed trends. 

PMID- 24863081
TI  - What are cancer centers advertising to the public?: a content analysis.
AB  - BACKGROUND: Although critics have expressed concerns about cancer center
      advertising, analyses of the content of these advertisements are lacking.
      OBJECTIVE: To characterize the informational and emotional content of direct-to
      consumer cancer center advertisements. DESIGN: Content analysis. SETTING: Top
      U.S. consumer magazines (n = 269) and television networks (n = 44) in 2012.
      MEASUREMENTS: Types of clinical services promoted; information provided about
      clinical services, including risks, benefits, costs, and insurance availability;
      use of emotional advertising appeals; and use of patient testimonials were
      assessed. Two investigators independently coded advertisements using ATLAS.ti,
      and kappa values ranged from 0.77 to 1.00. RESULTS: A total of 102 cancer centers
      placed 409 unique clinical advertisements in top media markets in 2012.
      Advertisements promoted treatments (88%) more often than screening (18%) or
      supportive services (13%). Benefits of advertised therapies were described more
      often than risks (27% vs. 2%) but were rarely quantified (2%). Few advertisements
      mentioned coverage or costs (5%), and none mentioned specific insurance plans.
      Emotional appeals were frequent (85%), evoking hope for survival (61%),
      describing cancer treatment as a fight or battle (41%), and inducing fear (30%).
      Nearly one half of advertisements included patient testimonials, which were
      usually focused on survival, rarely included disclaimers (15%), and never
      described the results that a typical patient may expect. LIMITATION: Internet
      advertisements were not included. CONCLUSION: Clinical advertisements by cancer
      centers frequently promote cancer therapy with emotional appeals that evoke hope
      and fear while rarely providing information about risks, benefits, costs, or
      insurance availability. Further work is needed to understand how these
      advertisements influence patient understanding and expectations of benefit from
      cancer treatments. PRIMARY FUNDING SOURCE: National Institutes of Health.

PMID- 24863083
TI  - [Analysis of elderly outpatients in relation to nutritional status, sarcopenia,
      renal function, and bone density].
AB  - OBJECTIVES: To evaluate relationships between nutritional status, sarcopenia and
      osteoporosis in older women. SUBJECTS AND METHODS: We studied 44 women, 67-94
      years, by mini-nutritional assessment (MAN), glomerular filtration corr. 1.73
      m(2), body mass index (BMI), arm circumference and calf (CP and CB), bone mineral
      density and body composition, DXA (fat mass MG; lean MM). We gauge sarcopenia:
      IMM MM = MSS + MIS/height(2). We used the Pearson correlation coefficient, p <
      0.05 as significant. RESULTS: MNA and IMM were positively correlated with BMI,
      CP, CB and MG. Age influenced negatively FG corr., BMI, FM, IMM and CP. Fourteen
      had a history of osteoporotic fractures. The lowest T-score was directly related
      to MAN and MG. CONCLUSIONS The aging caused the decline of FG, fat mass and
      muscle; the calf circumference, and brachial reflected nutritional status and
      body composition; and major influences on BMD were nutritional status and fat
      mass.

PMID- 24863084
TI  - [Analysis of an iodide radioimmunoassay for 11-deoxicortisol measurement].
AB  - OBJECTIVE: Our aim was to correlate 11-deoxycortisol levels obtained by two
      currently available techniques for 11-deoxycortisol measurement:
      radioimmunoassay, and high performance liquid chromatography followed by tandem
      mass spectrometry (MS/MS). The latter is the gold standard method for steroid
      hormone measurement. MATERIALS AND METHODS: We selected 88 samples and the
      results of these two methods were compared by Deming regression. RESULTS: The
      analytical sensitivity of the RIA was 0.30 ng/mL, with inadequate linearity and
      inadequate precision profile (34% of the samples had a CV >= 20%). From the
      selected samples, 54 had measurable levels of 11-deoxycortisol in both methods
      and were used in the comparison. The comparison of RIA with LC-MS/MS showed an
      overestimation of the results by RIA. The correlation coefficient was 0.610;
      linear regression slope was 3.751; and the intercept was 0.145, indicating a poor
      correlation between the two methods. CONCLUSION: We concluded that 11
      deoxycortisol measured by radioimmunoassay, despite a good analytical
      sensitivity, showed very low specificity, precluding its use as a reliable method
      for 11-deoxycortisol measurement.

PMID- 24863082
TI  - [Latin American consensus on hypertension in patients with diabetes type 2 and
      metabolic syndrome].
AB  - The present document has been prepared by a group of experts, members of
      cardiology, endocrinology, internal medicine, nephrology and diabetes societies
      of Latin American countries, to serve as a guide to physicians taking care of
      patients with diabetes, hypertension and comorbidities or complications of both
      conditions. Although the concept of metabolic syndrome is currently disputed, the
      higher prevalence in Latin America of that cluster of metabolic alterations has
      suggested that metabolic syndrome is a useful nosography entity in the context of
      Latin American medicine. Therefore, in the present document, particular attention
      is paid to this syndrome in order to alert physicians on a particular high-risk
      population, usually underestimated and undertreated. These recommendations result
      from presentations and debates by discussion panels during a 2-day conference
      held in Bucaramanga, in October 2012, and all the participants have approved the
      final conclusions. The authors acknowledge that the publication and diffusion of
      guidelines do not suffice to achieve the recommended changes in diagnostic or
      therapeutic strategies, and plan suitable interventions overcoming knowledge,
      attitude and behavioural barriers, preventing both physicians and patients from
      effectively adhering to guideline recommendations.

PMID- 24863085
TI  - Emerging trends in management of propionic acidemia.
AB  - OBJETIVO: To evaluate the therapeutic agents used during metabolic crises and in
      long-term management of patients with propionic acidemia (PA). MATERIALS AND
      METHODS: The records of PA patients were retrospectively evaluated. RESULTS: The
      study group consisted of 30 patients with 141 admissions. During metabolic
      crises, hyperammonemia was found in 130 (92%) admissions and almost all patients
      were managed with normal saline, >= 10% dextrose, and restriction of protein
      intake. In 56 (40%) admissions, management was done in intensive care unit, 31
      (22%) with mechanical ventilation, 10 (7%) with haemodialysis, 16 (11%) with
      vasopressor agents, and 12 (9%) with insulin. In the rescue procedure, L
      carnitine was used in 135 (96%) patients, sodium bicarbonate in 116 (82%), sodium
      benzoate in 76 (54%), and metronidazole in 10 (7%), biotin in about one-quarter,
      L-arginine in one third, and antibiotics in three-quarter of the admissions.
      Blood/packed RBCs were used in 28 (20%) patients, platelets in 26 (18%), fresh
      frozen plasma in 8 (6%), and granulocyte-colony stimulating factors in 10 (7%)
      admissions. All patients were managed completely/partially with medical nutrition
      formula plus amino acid mixture, vitamins and minerals. For long-term management
      24 (80%) patients were on L-carnitine, 22 (73%) on sodium benzoate, 6 (20%) on
      biotin, one half on alkaline therapy and 4 (13%) on regular metronidazole use.
      Almost all patients were on medical formula and regular follow-up. CONCLUSION:
      Aggressive and adequate management of acute metabolic crises with restriction of
      protein intake, stabilization of patient, reversal of catabolism, and removal of
      toxic metabolites are essential steps. Concerted efforts to ensure adequate
      nutrition, to minimize the risk of acute decompensation and additional
      therapeutic advances are imperative to improve the outcome of PA patients.

PMID- 24863086
TI  - [The effect of sibutramine on weight loss in obese adolescents].
AB  - OBJECTIVE: To evaluate the effect of sibutramine on weight loss in obese
      adolescents. SUBJECTS AND METHODS: A double-blind controlled study lasting 13
      months. The study included 73 obese adolescents of both sexes aged between 10 and
      18 years. Laboratory tests and imaging studies were performed before, during wash
      out, and at the end of 13 months. RESULTS: The percentage of patients who lost
      10% of their initial weight in the placebo group was 46%, and in the sibutramine
      group was 75%. When placebo was used, average weight rose by 1.61 kg, and BMI
      decreased by 0.24 kg/m(2) whereas with the use of sibutramine, weight decreased
      by 4.47 kg, and average BMI decreased, 2.38 kg/m(2), with p < 0.001. CONCLUSIONS:
      Sibutramine induced significantly more weight loss in obese adolescents compared
      with placebo, without significant side effects. The weight loss curve was
      different depending on the moment sibutramine was introduced. This finding
      indicates that the best time to start sibutramine is when adhesion begins to
      fail.

PMID- 24863087
TI  - Hypercholesterolemic diet induces hepatic steatosis and alterations in mRNA
      expression of NADPH oxidase in rat livers.
AB  - OBJECTIVE: This study aimed to determine whether a hypercholesterolemic diet
      induces hepatic steatosis, alterations in mRNA expression of NADPH oxidase
      subunits, and antioxidant defenses. MATERIALS AND METHODS: Fischer rats were
      divided into two groups of eight animals according to the treatment, control (C)
      and hypercholesterolemic diet (H). Those in group C were fed a standard diet (AIN
      93M), and those of the group H were fed a hypercholesterolemic diet (25% soybean
      oil and 1% cholesterol). RESULTS: The hypercholesterolemic diet did not affect
      body weight, but resulted in the accumulation of lipids in the liver, increased
      serum activities of aminotransferases and cholesterol levels. Biomarker of lipid
      peroxidation (TBARS) and mRNA expression of NADPH oxidase subunits p22(phox) and
      p47(phox) were increased in the liver of animals in group H. Besides, the
      activity and expression of antioxidant enzymes were altered. CONCLUSION: The
      results show increased mRNA expression of NADPH oxidase subunits and changes in
      antioxidant enzyme activities in diet-induced hepatic steatosis.

PMID- 24863088
TI  - Rare renal metastases from differentiated thyroid carcinoma: early clinical
      detection and treatment based on radioiodine.
AB  - OBJECTIVE: The aim of this study was to explore the clinical characteristics of
      renal metastatic cancer, the methods for its detection by radioiodine (131)I, and
      the response to (131)I treatment in fourteen patients with renal metastases from
      differentiated thyroid carcinoma (DTC). SUBJECTS AND METHODS: DTC patients (n =
      2,955) that received treatment with (131)I were retrospectively analyzed. Scans
      ((131)I-WBS, (31)I-SPECT/CT and/or (18)F-FDG-PET/CT) were performed after an oral
      therapeutic dose of (131)I. Therapeutic efficacy was evaluated based on changes
      in Tg and anatomical imaging changes at renal lesions. RESULTS: Among these 14
      patients, 11 had avidity for (131)I, but three patients did not accumulate (131)I
      after (131)I treatment. In the 11 (131)I-positive renal lesions, 10 cases were
      detected by (131)I-SPECT/CT combined with another imaging modality and one case
      by (131)I-WBS combined with ultrasonography (US). In the three (131)I-negative
      renal lesions, two cases were detected by 18F-FDG-PET/CT and one case by computed
      tomography (CT). In 11 patients with (131)I-avid renal metastases, Serum Tg
      levels in 81.82% (9/11) patients showed a gradual decline, and 18.18% (2/11) of
      the patients showed a significant elevation. There was no marked difference in
      serum Tg before the last (131)I treatment (Z = 0.157; p = 0.875). Only one
      patient presented partial response, eight patients exhibited stable disease, and
      renal metastases progressed in two patients showing progressive disease. No
      patients reached complete response. CONCLUSION: (131)I-SPECT/CT, combined with
      another imaging modality after (131)I-WBS, can contribute to the early detection
      of renal metastases of DTC. (131)I therapy is a feasible and effective treatment
      for most DTC renal metastases with avidity for (131)I.

PMID- 24863089
TI  - Celiac disease screening in Brazilian patients with osteoporosis.
AB  - OBJECTIVE: To analyze if it is worthwhile to screen Brazilian osteoporotic
      patients for celiac disease (CD). SUBJECTS AND METHODS: One hundred patients with
      osteoporosis and 97 controls were evaluated for IgA-EmA (IgA anti-endomysial
      antibodies) by indirect immunofluorescence method and IgG-anti-tTG (tissue
      transglutaminase) by ELISA assay. Positive patients were invited to have
      gastrointestinal endoscopy with jejunal biopsy. RESULTS: Two patients had
      positive IgG-anti-tTG test and one of them also showed positive IgA-EmA. Only the
      latter had a positive duodenal biopsy for CD. None of the controls were positive
      for either auto-antibodies. CONCLUSION: We observed low prevalence of CD in
      osteoporotic Brazilian patients. This finding does not support routine screening
      for CD in patients with osteoporosis in our geographic region.

PMID- 24863090
TI  - Exercise is associated with better quality of life in patients on TSH-suppressive
      therapy with levothyroxine for differentiated thyroid carcinoma.
AB  - OBJECTIVE: To evaluate if a supervised exercise training program improves the
      quality of life (QoL) of differentiated thyroid carcinoma (DTC) patients on TSH
      suppressive therapy with levothyroxine (L-T4). SUBJECTS AND METHODS: Initially, a
      cross-sectional study was performed to compare the QoL and the health-related
      quality of life (HRQoL) between subclinical hyperthyroidism (SCH) patients (n =
      33) and euthyroid subjects (EU; n = 49). In the prospective phase of the study,
      SCH patients were randomized in a non-blinded fashion to either participate (SCH
      Tr = trained patients; n = 16) or not (SCH-Sed = untrained patients; n = 17) in a
      supervised exercise training program. The exercise program consisted of 60
      minutes of aerobic and stretching exercises, twice a week, during twelve weeks.
      The QoL was assessed by the application of the WHOQOL-Bref, and the SF-36 was
      used to assess the HRQoL. RESULTS: SCH patients had statistically lower scores
      than EU on the "physical" domain of WHOQOL-Bref, besides "physical function",
      "role-physical", "bodily pain", "general health", "vitality", "role-emotional",
      and "mental-health" domains of SF-36. After three months, SCH-Tr patients showed
      improvement in the "physical" and "psychological" domains of WHOQOL-Bref (p <
      0.05), and in the "physical function", "role-physical", "bodily pain", "vitality"
      and "mental health" domains of SF-36. CONCLUSION: Patients on TSH-suppressive
      therapy with L-T4 for DTC had impaired QoL and HRQoL compared to EU, but it was
      improved after 3-months of an exercise training program. Exercise seems to play
      an important role in the follow-up of DTC patients, since it seems to minimize
      the adverse effects of the treatment on QoL and HRQoL.

PMID- 24863091
TI  - Iodine insufficiency in pregnant women from the State of Sao Paulo.
AB  - OBJECTIVE: The intake of adequate amounts of iodine during pregnancy is essential
      for the neurological development of the fetus. The aim of this study was to
      assess iodine nutrition status in pregnant women from the state of Sao Paulo,
      Brazil. MATERIAL AND METHODS: We analyzed urinary iodine concentration (UIC) in
      191 pregnant and 58 non-pregnant women matched by age. We used the World Health
      Organization criteria to define sufficient iodine supply (median UIC: 150-249
      ug/L among pregnant women, and 100-199 ug/L for non-pregnant women). RESULTS:
      Median UIC of the pregnant women studied was lower than the recommended value
      (median = 137.7 ug/L, 95% CI = 132.9 - 155.9), while non-pregnant women had UIC
      levels within the appropriate range (median = 190 MUg/L; 95% IC = 159.3-200.1).
      UIC was below 150 ug/L in 57% of the pregnant women. CONCLUSIONS: Although a
      larger sample is needed to consolidate these findings, these results raise
      concerns about the adequacy of the iodine supply of pregnant women in Brazil,
      especially considering the new determinations of the Brazilian government, which
      have recently reduced the concentrations of iodine in table salt to 15-45 mg/kg
      of salt.

PMID- 24863092
TI  - Effects of peptidic growth hormone secretagogue receptor (GHS-R) antagonist [D
      Lys3] on some of serum hormonal and biochemical parameters in Wistar rat model.
AB  - OBJECTIVE: The present study investigated the effects of different dosages of a
      GHS-R antagonist [D-Lys3] on some serum hormonal (cortisol, T3 and T4) and
      biochemical parameters in a rat. MATERIALS AND METHODS: Thirty-six 60-day-old
      male rats were assigned to four treatments. [D-Lys3]-GHRP-6 solutions were
      infused via intraperitoneal injections. Blood was collected and analyzed.
      RESULTS: The large dosages of a GHS-R antagonist (200 ng/kg BW) caused increases
      in cortisol, whereas no significant changes occurred when low dosages were
      injected. There were no significant changes in T3 and T4 following the
      administration of the GHS-R antagonist, but a considerable increase was observed
      in blood glucose levels of the groups (G50, G100, and G200 ng/kg BW). There was a
      significant increase in total protein when the greatest dose was administrated
      (G200 ng/kg BW). However, total cholesterol, triglycerides, and albumin showed no
      significant changes. CONCLUSIONS: Exogenous GHS-R antagonist can cause an
      increase in glucose and moderate increases in cortisol and total protein, yet it
      has no significant effect on T3 and T4 levels or on the concentrations of serum
      lipids. The effect of GHS-R antagonist is not completely adverse to the effects
      of ghrelin. Further molecular studies are necessary to identify the physiological
      effects of the peptidic GHS-R antagonist.

PMID- 24863093
TI  - Is thyroid stunning clinically relevant? A retrospective analysis of 208
      patients.
AB  - OBJECTIVE: Current guidelines have advised against the performance of (131)I
      iodide diagnostic whole body scintigraphy (dxWBS) to minimize the occurrence of
      stunning, and to guarantee the efficiency of radioiodine therapy (RIT). The aim
      of the study was to evaluate the impact of stunning on the efficacy of RIT and
      disease outcome. SUBJECTS AND METHODS: This retrospective analysis included 208
      patients with differentiated thyroid cancer managed according to a same protocol
      and followed up for 12-159 months (mean 30 +/- 69 months). Patients received RIT
      in doses ranging from 3,700 to 11,100 MBq (100 mCi to 300 mCi). Post-RIT-whole
      body scintigraphy images were performed 10 days after RIT in all patients. In
      addition, images were also performed 24-48 hours after therapy in 22 patients.
      Outcome was classified as no evidence of disease (NED), stable disease (SD) and
      progressive disease (PD). RESULTS: Thyroid stunning occurred in 40 patients
      (19.2%), including 26 patients with NED and 14 patients with SD. A multivariate
      analysis showed no association between disease outcome and the occurrence of
      stunning (p = 0.3476). CONCLUSION: The efficacy of RIT and disease outcome do not
      seem to be related to thyroid stunning.

PMID- 24863094
TI  - Maternal obesity and late effects on offspring metabolism.
AB  - OBJECTIVE: The aim of this study was to evaluate the late effects of maternal
      obesity induced by lesion of the ventromedial hypothalamus on offspring
      metabolism. MATERIALS AND METHODS: Thirty days after the bilateral lesion of the
      ventromedial hypothalamus, female rats were mated and divided into 2 groups of
      pregnant animals: Control (C) - false lesion (sham) and Obese (OB) - lesion.
      Three months after that, with the groups of mothers, offspring were divided into
      control and obese animals that received a normocaloric diet (C-N and OB-N), and
      control and obese animals that received a hypercaloric diet (C-H and OB-H). At
      120 days of age, the animals were euthanized and their carcasses, feces and food
      were submitted to calorimetric analysis to determine energy balance and body
      composition. RESULTS: During the growth period, offspring from obese mothers
      showed higher values of body weight and food intake than controls. Obese animals
      showed higher body weight gain and gross food efficiency than control animals in
      adulthood. The hypercaloric diet led to increased metabolizable energy intake,
      percentage of absorbed energy and energy expenditure in both groups. Body
      composition was only affected by the association of hypercaloric diet and
      maternal obesity that led to increased body fat. CONCLUSIONS: Maternal obesity
      has led to the development of later overweight in offspring, suggesting fetal
      programming. According to the trend presented, it is believed that the prolonged
      intake of hypercaloric diets in adult animals may, as an additional effect,
      induce worsening of the overweight induced by maternal obesity.

PMID- 24863095
TI  - [Hypothyroid polyneuropathy in a patient with autoimmune polyglandular syndrome
      type 2: case report].
AB  - The incidence of polyneuropathy in patients with hypothyroidism is not precisely
      known, but some studies report that about 25% to 42% of patients may show
      neuropathic clinical signs. We report a case of autoimmune poliglandular syndrome
      type 2 (APS-2), whose initial presentation was hypothyroid polyneuropathy. A 41
      year-old man complained of slowly progressive paresthesias and weakness affecting
      all four limbs, and associated with frequent drowsiness, weakness, cold
      intolerance, dizziness, nausea, and craving for salt. General physical
      examination showed hyperpigmentation of skin and mucous membranes, and
      hypotension. Neurological examination showed global, deep, and symmetrical
      hyporeflexia with slight signs of superficial hypoesthesia in the limbs.
      Electrodiagnostic studies (ENMG) together with laboratory tests, confirmed the
      suspicion of Hashimoto's thyroiditis associated with Addison's disease featuring
      the picture of APS-2. The patient was treated with fludrocortisone 0.05 mg/day
      and levothyroxine 100 mcg/day, and showed gradual and complete resolution of
      complaints. Changes were found in general physical and neurological examinations.
      ENMG repeated six months later showed complete resolution of neuropathy. This
      report shows a rare case of APS-2 presented as polyneuropathy hypothyroidism, and
      reinforces the importance of dosing thyroid hormone in polyneuropathy syndromes.
      Levothyroxine replacement was shown to be effective in reversing clinical and
      electrophysiologic neuropathy.

PMID- 24863096
TI  - Successful parathyroid tissue autograft after 3 years of cryopreservation: a case
      report.
AB  - After a total parathyroidectomy, well-established protocols for the
      cryopreservation of parathyroid tissue and for the delayed autograft of this
      tissue exist, especially in cases of secondary hiperparathyroidism (HPT) or
      familial or sporadic parathyroid hyperplasia. Although delayed autografts are
      effective, the published success rates vary from 10% to 83%. There are numerous
      factors that influence the viability, and therefore the success, of an autograft,
      including cryopreservation time. Certain authors believe that the tissue is only
      viable for 24 months, but there is no consensus on how long the parathyroid
      tissue can be preserved. A 63-year-old male who was diagnosed with sporadic
      multiple endocrine neoplasia type 1 and primary hyperparathyroidism, and was
      submitted to a total parathyroidectomy and an autograft in the forearm. The
      implant failed, and the patient developed severe hypoparathyroidism in the months
      following the surgery. Thirty-six months after the total parathyroidectomy, the
      cryopreserved autograft was successfully transplanted, and hypoparathyroidism was
      reversed (most recent systemic parathyroid hormone, PTH, of 36 pg/mL, and total
      calcium of 9.1 mg/dL; no oral calcium supplementation). The case presented here
      indicates that cryopreserved parathyroid tissue may remain viable after 24 months
      in storage, and may retain the capacity to reverse permanent postsurgical
      hypoparathyroidism. These data provide reasonable evidence that the time limit
      for cryopreservation remains undetermined and that additional research would be
      valuable.

PMID- 24863098
TI  - Continuous flow two-dimensional acoustic orientation of nonspherical cells.
AB  - Flow cytometry is a frequently used method when it comes to cell sorting and
      analysis. Nonspherical cells, such as red blood cells or sperm cells, however,
      pose a challenge as they reduce the precision of light scatter measurements which
      interfere with the analysis of these and other cell populations in the same
      sample. Here, we present a microfluidic chip for acoustophoresis utilizing
      ultrasonic standing waves to focus and orient red blood cells in two dimensions
      in the channel center. The cells can be oriented to show either their flat or up
      ended side toward the optical axis and the observer. In an acoustic standing wave
      field the cells will be rotated until the direction of the smallest dimension is
      parallel with the direction where the acoustic energy is strongest. While keeping
      the cells focused in the channel center utilizing acoustic resonances in two
      dimensions, the orientation can be controlled by increasing the acoustic energy
      in either the horizontal or vertical resonance mode. It was shown that 87.8 +/-
      3.8% of the red blood cells could be horizontally oriented while 98.7 +/- 0.3%
      could be vertically oriented. The ability to control the orientation of
      nonspherical cells with high accuracy is a beneficial feature and potential
      contribution to the rapidly growing field of flow and image cytometry. 

PMID- 24863097
TI  - The role of staging MRI in predicting apical margin positivity for robot-assisted
      laparoscopic radical prostatectomy.
AB  - PURPOSE: To investigate the association between apical margin positivity and
      preoperative magnetic resonance imaging (MRI) in patients who have undergone
      robot-assisted laparoscopic radical prostatectomy (RARP). PATIENTS AND METHODS:
      From September 2010 through November 2012, we treated 84 Japanese men with
      clinically localized prostate cancer with RARP. The excised specimens, which were
      divided into right and left fragments, were evaluated for the presence of
      positive surgical margins (PSMs) and preoperative MRI findings. RESULTS: The
      overall PSM rate was 21.4% (18 of 84 patients), 83.3% (15 of 18 cases) of which
      were situated in the apex. Evaluating the prostate divided into right and left
      fragments, the PSM rate was 10.7% at the apex (18 of 168 fragments). Cancer was
      suspected via preoperative MRI in 39 fragments (23.2%) and detected in the
      prostatic apex by prostate biopsy in 67 fragments (39.9%). Multiple regression
      analysis revealed that MRI and nerve-sparing procedures significantly indicate
      apical margin positivity (p = 0.005). CONCLUSIONS: The prostatic apex is the most
      common location of PSMs after RARP. Our results demonstrate that preoperative MRI
      for cancer of the prostatic apex may provide substantial information and enable
      complete cancer clearance.

PMID- 24863100
TI  - Two frequent mutations associated with the classic form of propionic acidemia in
      Taiwan.
AB  - Propionyl-CoA carboxylase (PCC) is involved in the catabolism of branched chain
      amino acids, odd-numbered fatty acids, cholesterol, and other metabolites. PCC
      consists of two subunits, alpha and beta, encoded by the PCCA and PCCB genes,
      respectively. Mutations in the PCCA or PCCB subunit gene may lead to propionic
      acidemia. In this study, we performed mutation analysis on ten propionic acidemia
      patients from eight unrelated and nonconsanguineous families in Taiwan. Two PCCA
      mutations, c.229C->T (p.R77W) and c.1262A->C (p.Q421P), were identified in a PCCA
      deficient patient. Six mutations in the PCCB gene, including c.-4156_183+3713del,
      c.580T->C (p.S194P), c.838dup (p.L280Pfs 11), c.1301C->T (p.A434V), c.1316A->G
      (P.Y439C), and c.1534C->T (p.R512C), were identified in seven PCCB-deficient
      families. The c.-4156_183+3713del mutation is the first known large deletion that
      affects the PCCB gene functions. Furthermore, the c.1301C->T and c.
      4156_183+3713del mutations in the PCCB gene have not been reported previously.
      Clinical features demonstrated that these two frequent mutations are associated
      with low enzyme activity and a classic propionic acidemia phenotype.

PMID- 24863101
TI  - Delineating ion-ion interactions by electrostatic modeling for predicting
      rhizotoxicity of metal mixtures to lettuce Lactuca sativa.
AB  - Effects of ion-ion interactions on metal toxicity to lettuce Lactuca sativa were
      studied based on the electrical potential at the plasma membrane surface (psi0 ).
      Surface interactions at the proximate outside of the membrane influenced ion
      activities at the plasma membrane surface ({M(n+)}0). At a given free Cu(2+)
      activity in the bulk medium ({Cu(2+)}b), additions of Na(+), K(+), Ca(2+), and
      Mg(2+) resulted in substantial decreases in {Cu(2+)}0. Additions of Zn(2+) led to
      declines in {Cu(2+)}0, but Cu(2+) and Ag(+) at the exposure levels tested had
      negligible effects on the plasma membrane surface activity of each other. Metal
      toxicity was expressed by the {M(n+)}0 -based strength coefficient, indicating a
      decrease of toxicity in the order: Ag(+)  > Cu(2+)  > Zn(2+). Adsorbed Na(+),
      K(+), Ca(2+), and Mg(2+) had significant and dose-dependent effects on Cu(2+)
      toxicity in terms of osmolarity. Internal interactions between Cu(2+) and Zn(2+)
      and between Cu(2+) and Ag(+) were modeled by expanding the strength coefficients
      in concentration addition and response multiplication models. These extended
      models consistently indicated that Zn(2+) significantly alleviated Cu(2+)
      toxicity. According to the extended concentration addition model, Ag(+)
      significantly enhanced Cu(2+) toxicity whereas Cu(2+) reduced Ag(+) toxicity. By
      contrast, the response multiplication model predicted insignificant effects of
      adsorbed Cu(2+) and Ag(+) on the toxicity of each other. These interactions were
      interpreted using psi0, demonstrating its influence on metal toxicity.

PMID- 24863099
TI  - Flicker-induced retinal vasodilatation is not dependent on complement factor H
      polymorphism in healthy young subjects.
AB  - PURPOSE: The complement factor H (CFH) tyrosine 402 histidine (Y402H, rs1061170)
      variant is known to be significantly associated with age-related macular
      degeneration (AMD). Whether this genetic variant may impact retinal blood flow
      regulation is largely unknown. This study investigated whether flicker-induced
      vasodilation, an indicator for the coupling between neural activity and blood
      flow, is altered in subjects carrying the rs1061170 risk allele. METHODS: One
      hundred healthy subjects (aged between 18 and 45 years) were included in this
      study. Retinal blood flow regulation was tested by assessing retinal vessel
      calibres in response to stimulation with diffuse flicker light. Retinal vascular
      flicker responses were determined with a Dynamic Vessel Analyzer (DVA). In
      addition, genotyping for rs1061170 was performed. RESULTS: Eighteen subjects were
      homozygous for the risk allele C, 50 were homozygous for the ancestral allele T,
      and 31 subjects were heterozygous (CT). One subject had to be excluded from data
      evaluation, as no genetic analysis could be performed due to technical
      difficulties. Baseline diameters of retinal arteries (p = 0.39) and veins (p =
      0.64) were comparable between the three groups. Flicker-induced vasodilation in
      both retinal arteries (p = 0.38) and retinal veins (p = 0.62) was also comparable
      between the three studied groups. CONCLUSIONS: Our data indicate that homozygous
      healthy young carriers of the C risk allele at rs1061170 do not show abnormal
      flicker-induced vasodilation in the retina. This suggests that the high-risk
      genetic variant of CFH polymorphism does not impact neuro-vascular coupling in
      healthy subjects.

PMID- 24863103
TI  - Syncope at altitude: an enigmatic case.
AB  - We report a case of a young boy with recurrent episodes of syncope at elevated
      altitude. While not conforming to common presentations of altitude sickness, the
      differential diagnoses and possible etiologies are discussed.

PMID- 24863102
TI  - Ultrafast 3D spin-echo acquisition improves Gadolinium-enhanced MRI signal
      contrast enhancement.
AB  - Long scan times of 3D volumetric MR acquisitions usually necessitate ultrafast in
      vivo gradient-echo acquisitions, which are intrinsically susceptible to magnetic
      field inhomogeneities. This is especially problematic for contrast-enhanced (CE)
      MRI applications, where non-negligible T2* effect of contrast agent deteriorates
      the positive signal contrast and limits the available range of MR acquisition
      parameters and injection doses. To overcome these shortcomings without degrading
      temporal resolution, ultrafast spin-echo acquisitions were implemented.
      Specifically, a multiplicative acceleration factor from multiple spin echoes
      (*32) and compressed sensing (CS) sampling (*8) allowed highly-accelerated 3D
      Multiple-Modulation-Multiple-Echo (MMME) acquisition. At the same time, the CE
      MRI of kidney with Gd-DOTA showed significantly improved signal enhancement for
      CS-MMME acquisitions (*7) over that of corresponding FLASH acquisitions (*2).
      Increased positive contrast enhancement and highly accelerated acquisition of
      extended volume with reduced RF irradiations will be beneficial for oncological
      and nephrological applications, in which the accurate in vivo 3D quantification
      of contrast agent concentration is necessary with high temporal resolution. 

PMID- 24863105
TI  - Disseminated BCG in an infant with interleukin-12 receptor B1 (IL12RB1)
      deficiency.
AB  - Although neonatal vaccination with bacille Calmette-Guerin (BCG) is considered to
      be safe, complications with disseminated disease are associated with underlying
      immuno-deficiency disorders. A BCG-vaccinated 4-month-old girl of Sri Lankan
      parentage developed progressive left axillary lymphadenopathy and severe
      bronchopneumonia. Lymph node biopsy demonstrated epithelioid granulomata and acid
      fast bacilli. An older sibling had had a similar clinical presentation and the
      outcome had been fatal. Investigation for immuno-deficiency detected complete
      IL12RB1 deficiency. Full recovery followed a prolonged course of anti-tuberculous
      chemotherapy. She was put on lifelong isoniazid prophylaxis. In HIV-negative
      infants with unusual complications related to BCG vaccination, a primary immuno
      deficiency disorder should be considered. 

PMID- 24863106
TI  - The journey toward high performance and excellent quality.
AB  - Signalling the importance of healthcare quality and quality improvement plans in
      Ontario, the province's Excellent Care for all act requires all hospitals to
      publish quality improvement plans, conduct regular patient and staff surveys, and
      forge a clear link between hospital CEO compensation and quality improvement. The
      act also clarifies and strengthens links between evidence and quality of care.
      The act is an important step toward Ontario's becoming a high-performing
      healthcare system. Yet as some of the papers in this special issue of Healthcare
      Quarterly discuss, there remains much to be done. Other papers and interviews
      draw attention to the importance of strategic and system design levers-
      particularly setting goals, public reporting of results and clinician engagement-
      to stimulating improvement. Yet other papers present a diverse range of
      perspectives and ideas on how to pursue improvement and to bridge the knowing
      doing gap in healthcare so that evidence informs better practice. Achieving and
      sustaining high performance in healthcare will require dedicated effort by
      everyone in every healthcare organization. With a view to the future, the act
      allows for the expansion of the quality obligations initially applicable to
      hospitals to other publicly funded health organizations.

PMID- 24863107
TI  - Patient-and family-centredness: growing a sustainable culture.
AB  - Elements of a sustainable culture that nourishes patient- and family-centredness
      (PFC) in healthcare are elegantly simple, but achieving PFC poses profound
      challenges for healthcare systems and policy. Healthcare organizations and policy
      makers often identify tactics and tools that they believe enhance PFC, but they
      fail to involve the very people who use healthcare services: patients, their
      families and community members. A way of viewing the journey to a sustainable PFC
      culture is by examining those elements of leadership, partnership and
      infrastructure that are necessary for its achievement. 

PMID- 24863108
TI  - A relentless commitment to improvement: the Guelph General Hospital experience.

PMID- 24863104
TI  - Distinguishing informational from value-related encoding of rewarding and
      punishing outcomes in the human brain.
AB  - There is accumulating evidence implicating a set of key brain regions in encoding
      rewarding and punishing outcomes, including the orbitofrontal cortex, medial
      prefrontal cortex, ventral striatum, anterior insula, and anterior cingulate.
      However, it has proved challenging to reach consensus concerning the extent to
      which different brain areas are involved in differentially encoding rewarding and
      punishing outcomes. Here, we show that many of the brain areas involved in
      outcome processing represent multiple outcome components: encoding the value of
      outcomes (whether rewarding or punishing) and informational coding, i.e.
      signaling whether a given outcome is rewarding or punishing, ignoring magnitude
      or experienced utility. In particular, we report informational signals in the
      lateral orbitofrontal cortex and anterior insular cortex that respond to both
      rewarding and punishing feedback, even though value-related signals in these
      areas appear to be selectively driven by punishing feedback. These findings
      highlight the importance of taking into account features of outcomes other than
      value when characterising the contributions of different brain regions in outcome
      processing. 

PMID- 24863109
TI  - Public engagement in Ontario's hospitals--opportunities and challenges.
AB  - The Excellent Care for All Act strengthens the accountability of healthcare
      provider organizations to the public. However, the ways in which healthcare
      organizations have engaged the public have often been limited. There are a number
      of organizations and approaches described in this paper that have exceeded
      existing public governance and input processes by involving, engaging and
      partnering with the public. Their processes range from engaging with patients to
      improve the quality, safety and appropriateness of healthcare services to
      approaches that strengthen organizational decision making and strategic planning.

PMID- 24863110
TI  - Organization culture and managerial discipline key to quality improvement: the
      Mount Sinai Hospital experience.

PMID- 24863111
TI  - A ten-year history: the Cancer Quality Council of Ontario.
AB  - One of the longest-established quality oversight organizations in Canadian
      healthcare, the Cancer Quality Council of Ontario (CQCO) is an advisory group
      formed in 2002 by the Ministry of Health and Long-Term Care. Although quasi
      independent from Cancer Care Ontario (CCO), the council was established to
      provide advice to CCO and the ministry in their efforts to improve the quality of
      cancer care in the province. The council is composed of a multidisciplinary group
      of healthcare providers, cancer survivors and experts in the areas of oncology,
      health system policy and administration, governance, performance measurement and
      health services research. Its mandate is to monitor and report publicly on the
      performance of the Ontario cancer system and to motivate improvement through
      national and international benchmarking. Since its formation, the council has
      played an evolving role in improving the quality of care received by Ontario
      cancer patients. This article will briefly describe the origins and founding
      principles of the CQCO, its changing role in monitoring quality and its
      relationship with CCO. 

PMID- 24863112
TI  - Aligning and pursuing quality goals: the role of Health Quality Ontario.

PMID- 24863113
TI  - It's about the relationships: reflections from a provincial quality council on
      building a better healthcare system.
AB  - The mandate of Saskatchewan's Health Quality Council (HQC) is to play a hands-on
      role in health system transformation by working collaboratively with government,
      regional health authorities, health professions and citizens. Instead of the
      traditional, representative model, HQC is governed by an "expert board." Because
      board members do not represent their own organization or profession, they have
      stayed focused on the "system" nature of HQC's mandate, working with individuals
      and organizations committed to improving quality at a system level. In recent
      years, HQC has achieved a significant shift in attitude toward quality
      improvement throughout Saskatchewan's healthcare system, realized partly through
      building strong, effective relationships with those managing and delivering care.
      Hundreds of front-line providers, managers and leaders are now learning and
      applying quality improvement methods to improve healthcare quality. Since its
      inception, HQC has moved to a higher level of interdependence with other
      healthcare system stakeholders, helping advance the quality agenda so that
      everyone has a greater understanding about mutual responsibilities. 

PMID- 24863114
TI  - The Excellent Care for All Act's quality improvement plans: reflections on the
      first year.
AB  - In 2010, Ontario passed the Excellent Care for All Act (the EFCA Act). Although
      the purpose of the Act was clear, the legislation itself was relatively non
      prescriptive in relation to the mandatory quality improvement plans (QIPs), and
      hospitals needed direction on how to proceed. A task group was established to
      develop a common provincial QIP template, along with guidance, support and
      educational materials. The template was field tested across the province and,
      subsequently, all hospitals developed their QIPs, posted them publicly, and
      submitted them to Health Quality Ontario (HQO). Despite challenges including
      short time frames, limitations in data availability and a variance of skills in
      performance measurement, the implementation of QIPs in hospitals was a success.
      Success is part could be attributed to a strong tripartite partnership and good
      communication channels with hospitals. Hospitals with the most effective QIPs
      were those whose leaders used the opportunity of a provincially mandated QIP as a
      lever to drive and legitimize the need to have conversations regarding quality
      from the boardroom down to the front line. As organizations continue to develop
      and implement their QIPs, we will see this tremendous quality improvement effort
      sustained. The QIPs will remain a significant transformational lever to engage
      the system in improving performance and achieving excellent care for all. 

PMID- 24863115
TI  - The crucial role of clinician engagement in system-wide quality improvement: the
      Cancer Care Ontario experience.
AB  - In 2004, Cancer Care Ontario's (CCO) role changed from providing direct cancer
      service to oversight, with a mission to improve the performance of the cancer
      system by driving quality, accountability and innovation in all cancer-related
      services. Since then, CCO has built a model for province-wide quality improvement
      and oversight--the Performance Improvement Cycle--that exemplifies the key
      elements of the Excellent Care for All Act, 2010. While ensuring that quality of
      the cancer system is by necessity a continuous process, the approach taken thus
      far has achieved measurable results and will continue to form the basis of CCO's
      future work. Clinician engagement has been critical to the success of CCO's
      approach to quality oversight and improvement. CCO uses a variety of formal and
      informal clinical engagement structures at each step of the Performance
      Improvement Cycle, and has developed operational processes to support quality
      improvement, and educational and mentorship programs to build clinician
      leadership capacity in that area. An example of sustained quality improvement in
      system performance is illustrated in a case study of the surgical treatment of
      prostate cancer. The improvement was achieved with strong collaboration across
      CCO's surgery and pathology clinical programs, with support from informatics
      staff.

PMID- 24863116
TI  - Engaging clinicians through intrinsic incentives.

PMID- 24863117
TI  - Governance for quality and patient safety: the impact of the Ontario Excellent
      Care for All Act, 2010.
AB  - The passage of the Excellent Care for All Act, 2010 (ECFA Act) in Ontario has
      confirmed the responsibilities of hospital boards for quality of care and
      reinforced expectations that they will monitor performance and establish
      strategic aims in this area. Quality of care and patient safety have created a
      new agenda for many healthcare boards that had only a limited focus on these
      issues. Here, we report on interviews with five Ontario healthcare organizations
      identified by experts as having high-performing boards. Our question was, how has
      the ECFA Act influenced Ontario healthcare organizations' governance practices
      relating to quality and safety? While the act has raised the profile of these
      issues, in the short-term it may have blunted the effectiveness of some boards
      that had already developed a clear strategic focus on quality and patient safety.
      Executive compensation was the most contentious issue; the introduction of pay
      for performance was considered poor timing, given the Ontario government's pay
      freeze. Overall, the act is an important step in increasing responsible
      governance and has helped align governance activities with the core work of
      hospitals--delivering high-quality care. However, effective policy must create an
      environment where all organizations focus on improvement, but where regulation
      does not limit the capabilities of leading organizations to achieve even higher
      performance.

PMID- 24863119
TI  - Clinicians as designers and leaders of quality improvement.

PMID- 24863118
TI  - Improving care for British Columbians: the critical role of physician engagement.
AB  - Canadian provinces are addressing quality of care and patient safety in a
      systemic way, but obtaining physician involvement in system improvement continues
      to be a challenge. To address this issue, individual physicians, physician
      groups, the British Columbia Medical Association, the health authorities, the BC
      Patient Safety & Quality Council (BCPSQC) and the Ministry of Health have come
      together to support physician involvement and foster physician satisfaction.
      Building on earlier work on patient safety, in 2010 the ministry developed a
      comprehensive strategy for system-wide improvement, focusing on achieving
      critical population, patient and sustainability outcomes. Central to this plan is
      the acknowledged need to involve healthcare providers of all disciplines, in
      particular physicians. Today, BC physicians are leading large-scale provincial
      clinical improvement in three interdependent areas: Clinical Care Management,
      Integrated Primary and Community Care, and the National Surgical Quality
      Improvement Program. To further physicians' key contributions to BC's healthcare
      system, the BCPSQC, physician-ministry committees, health authorities and the
      Ministry will continue to engage physicians through practice support, feedback,
      financial recognition and information exchange, and by supporting improvements in
      the care provided to patients. 

PMID- 24863120
TI  - Supporting the use of research evidence in the Canadian health sector.
AB  - Interventions to support evidence-informed decision making have increased in
      recent years, but they are often fragmented across different clinical, management
      and policy environments. Many of these efforts also place varying emphasis on
      supporting the use of research evidence, with some choosing to focus more on
      expert knowledge and/or media coverage and others focusing on supporting the use
      of actionable messages arising from high-quality, relevant and optimally packaged
      research evidence. In this paper, we profile five Canadian contributions-
      EvidenceUpdates, Rx for Change, Health-Evidence.ca, Health Systems Evidence and
      the McMaster Health Forum--that allow providers, managers and policy makers to
      efficiently find and use research evidence when they need it. These contributions
      are critical for supporting both local and global efforts to provide optimal and
      cost-effective care, improving the quality of care and strengthening health
      systems.

PMID- 24863121
TI  - Bringing evidence to healthcare decision making.

PMID- 24863122
TI  - Evidence and quality, practicalities and judgments: some experience from NICE.
AB  - The National Institute for Health and Clinical Excellence (NICE) is the principal
      provider of information about the evidence relating to effectiveness and cost
      effectiveness in healthcare in the National Health Service of England and Wales.
      NICE regards quality as primarily to do with effectiveness, safety and the
      patient experience. In this paper we comment on the quality of evidence regarding
      these three and speculate about the consequences of widening the range of
      interventions for appraisal and taking more complete account of upstream
      determinants of health. We also comment on the type and quality of the evidence,
      as well as the way in which it is used, and the values--too often hidden--that
      permeate both the evidence and the way in which it is used.

PMID- 24863123
TI  - Stronger policy through evidence.

PMID- 24863124
TI  - Who doesn't deserve excellent care?
AB  - Discussion on implementation of the Excellent Care for all Act, 2010 (ECFA Act),
      Bill 46, has focused on the hospital sector in Ontario, but it also has relevance
      outside the hospital setting. As primary healthcare, long-term care and home care
      all receive public funding, these sectors should be expected to be compliant with
      Bill 46. But does the act also govern government-funded (i.e., by other than the
      Ministry of Health and Long-Term Care) community-based programs such as adult day
      programs, meals-on-wheels, nutrition programs for children, and more? We propose
      that we cannot exclude any of these essential programs. We also consider the non
      hospital sector and health organizations that do not receive public funding. The
      healthcare system will be well served if we consider whether the EFCA Act's key
      elements should be implemented across the system both vertically and
      horizontally. Vertical implementation in the hospital sector could be followed by
      primary care, home and community care, long-term care, and the rest of the
      vertical silos within the healthcare system. But by taking the horizontal
      approach, all sectors within and outside of what we traditionally think of health
      would be integrated using an evidence-informed and outcome-based approach and
      methodology. 

PMID- 24863125
TI  - Building better healthcare facilities through evidence-based design: breaking new
      ground at Vancouver Island Health Authority.
AB  - Many of today's healthcare facilities were constructed at least 50 years ago, and
      a growing number have outlived their useful lives. Despite renovations and
      renewals, they often fall short of providing an appropriate care setting.
      Clinicians and staff develop a mixture of compromises and workarounds simply to
      make things function. Evidence-based design principles are often absent from new
      healthcare facilities, perhaps because of lack of awareness of the principles or
      because implementing them may fall foul of short-term and short-sighted budgetary
      decisions. In planning a new healthcare facility in 2008, the executive team at
      Vancouver Island Health Authority decided to adopt the evidence-based design
      approach. They conducted site visits to newly constructed hospitals across North
      America and beyond, to determine best practices in terms of design and
      construction. These engagements resulted in the implementation of 102 evidence
      based design principles and attributes in Victoria's Royal Jubilee hospital, a
      500-bed Patient Care Centre. This $350M project was completed on time and on
      budget, showing that using evidence need not result in delays or higher costs. To
      date, the results of the evidence-based design are promising, with accolades
      coming from patients, staff and clinical partners, and a number of immediate and
      practical benefits for patients, families and care teams alike. 

PMID- 24863126
TI  - Quality legislation: lessons for Ontario from abroad.
AB  - While the Excellent Care for All Act, 2010 (ECFA Act) provides a comprehensive
      approach to stimulating quality improvement in healthcare, there are other
      examples of legislations articulating strategies aimed at the same goal but
      proposing different approaches. This paper reviews quality of care legislations
      in the Netherlands, the United States, England and Australia, compares those
      pieces of legislation with the ECFA Act and suggests lessons for Ontario in
      planning the next stages of its healthcare quality strategy. Notable among the
      commonalities that the EFCA Act shares with the selected examples of legislation
      are mandatory reporting of performance results at an organizational level and
      furthering quality improvement, evidence generation and performance monitoring.
      However, the EFCA Act does not include any elements of restructuring or
      competition, unlike some of the other examples. Key to successful transformation
      of the Ontario healthcare system will be to propose a package of changes that
      will deal systematically with all aspects of transformation sought (including
      structural changes, payments systems and elements of competition), will garner
      support from all the actors, and will be implemented consistently and
      persistently. Benchmarking on the implementation and impact of reforms with the
      countries presented in this paper may be an additional important step. Quality of
      care is a key focus of health system reforms, and in recent years many countries
      in the Organisation of Economic Co-operation and Development (OECD), including
      Canada, have developed strategies aimed at improving healthcare quality and
      patient safety (OECD 2010). Ovretveit and Klazinga propose that national
      strategies for quality of care can be targeted at different types of health
      system stakeholders: professionals, healthcare organizations, medical products
      and technologies, patients and financers (World Health Organization Regional
      Office for Europe 2008). The generic elements of these strategies relate to
      legislation and regulation, monitoring and measurement; assuring and improving
      the quality and safety of individual healthcare services, and assuring and
      improving the quality of the healthcare system as a whole. Various combinations
      of quality improvement approaches (such as quality assessment, standards-based
      quality management, team problem solving, and patient and community
      participation) are suitable for these functions as part of the respective quality
      strategies. 

PMID- 24863127
TI  - Reduction of selenite by Azospirillum brasilense with the formation of selenium
      nanoparticles.
AB  - The ability to reduce selenite (SeO(3)(2-)) ions with the formation of selenium
      nanoparticles was demonstrated in Azospirillum brasilense for the first time. The
      influence of selenite ions on the growth of A. brasilense Sp7 and Sp245, two
      widely studied wild-type strains, was investigated. Growth of cultures on both
      liquid and solid (2 % agar) media in the presence of SeO(3)(2-) was found to be
      accompanied by the appearance of the typical red colouration. By means of
      transmission electron microscopy (TEM), electron energy loss spectroscopy (EELS)
      and X-ray fluorescence analysis (XFA), intracellular accumulation of elementary
      selenium in the form of nanoparticles (50 to 400 nm in diameter) was demonstrated
      for both strains. The proposed mechanism of selenite-to-selenium (0) reduction
      could involve SeO(3)(2-) in the denitrification process, which has been well
      studied in azospirilla, rather than a selenite detoxification strategy. The
      results obtained point to the possibility of using Azospirillum strains as
      endophytic or rhizospheric bacteria to assist phytoremediation of, and cereal
      cultivation on, selenium-contaminated soils. The ability of A. brasilense to
      synthesise selenium nanoparticles may be of interest to nanobiotechnology for
      "green synthesis" of bioavailable amorphous red selenium nanostructures.

PMID- 24863128
TI  - Pioneer microbial communities of the Fimmvorduhals lava flow, Eyjafjallajokull,
      Iceland.
AB  - Little is understood regarding the phylogeny and metabolic capabilities of the
      earliest colonists of volcanic rocks, yet these data are essential for
      understanding how life becomes established in and interacts with the planetary
      crust, ultimately contributing to critical zone processes and soil formation.
      Here, we report the use of molecular and culture-dependent methods to determine
      the composition of pioneer microbial communities colonising the basaltic
      Fimmvorduhals lava flow at Eyjafjallajokull, Iceland, formed in 2010. Our data
      show that 3 to 5 months post eruption, the lava was colonised by a low-diversity
      microbial community dominated by Betaproteobacteria, primarily taxa related to
      non-phototrophic diazotrophs such as Herbaspirillum spp. and chemolithotrophs
      such as Thiobacillus. Although successfully cultured following enrichment,
      phototrophs were not abundant members of the Fimmvorduhals communities, as
      revealed by molecular analysis, and phototrophy is therefore not likely to be a
      dominant biogeochemical process in these early successional basalt communities.
      These results contrast with older Icelandic lava of comparable mineralogy, in
      which phototrophs comprised a significant fraction of microbial communities, and
      the non-phototrophic community fractions were dominated by Acidobacteria and
      Actinobacteria.

PMID- 24863129
TI  - Parasite fitness traits under environmental variation: disentangling the roles of
      a chytrid's immediate host and external environment.
AB  - Parasite environments are heterogeneous at different levels. The first level of
      variability is the host itself. The second level represents the external
      environment for the hosts, to which parasites may be exposed during part of their
      life cycle. Both levels are expected to affect parasite fitness traits. We
      disentangle the main and interaction effects of variation in the immediate host
      environment, here the diatom Asterionella formosa (variables host cell volume and
      host condition through herbicide pre-exposure) and variation in the external
      environment (variables host density and acute herbicide exposure) on three
      fitness traits (infection success, development time and reproductive output) of a
      chytrid parasite. Herbicide exposure only decreased infection success in a low
      host density environment. This result reinforces the hypothesis that chytrid
      zoospores use photosynthesis-dependent chemical cues to locate its host. At high
      host densities, chemotaxis becomes less relevant due to increasing chance contact
      rates between host and parasite, thereby following the mass-action principle in
      epidemiology. Theoretical support for this finding is provided by an agent-based
      simulation model. The immediate host environment (cell volume) substantially
      affected parasite reproductive output and also interacted with the external
      herbicide exposed environment. On the contrary, changes in the immediate host
      environment through herbicide pre-exposure did not increase infection success,
      though it had subtle effects on zoospore development time and reproductive
      output. This study shows that both immediate host and external environment as
      well as their interaction have significant effects on parasite fitness.
      Disentangling these effects improves our understanding of the processes
      underlying parasite spread and disease dynamics. 

PMID- 24863130
TI  - Corrosion of iron by iodide-oxidizing bacteria isolated from brine in an iodine
      production facility.
AB  - Elemental iodine is produced in Japan from underground brine (fossil salt water).
      Carbon steel pipes in an iodine production facility at Chiba, Japan, for brine
      conveyance were found to corrode more rapidly than those in other facilities. The
      corroding activity of iodide-containing brine from the facility was examined by
      immersing carbon steel coupons in "native" and "filter-sterilized" brine samples.
      The dissolution of iron from the coupons immersed in native brine was threefold
      to fourfold higher than that in the filter-sterilized brine. Denaturing gradient
      gel electrophoresis analyses revealed that iodide-oxidizing bacteria (IOBs) were
      predominant in the coupon-containing native brine samples. IOBs were also
      detected in a corrosion deposit on the inner surface of a corroded pipe. These
      results strongly suggested the involvement of IOBs in the corrosion of the carbon
      steel pipes. Of the six bacterial strains isolated from a brine sample, four were
      capable of oxidizing iodide ion (I(-)) into molecular iodine (I(2)), and these
      strains were further phylogenetically classified into two groups. The iron
      corroding activity of each of the isolates from the two groups was examined. Both
      strains corroded iron in the presence of potassium iodide in a concentration
      dependent manner. This is the first report providing direct evidence that IOBs
      are involved in iron corrosion. Further, possible mechanisms by which IOBs
      corrode iron are discussed.

PMID- 24863131
TI  - Bacterial community structure in patagonian Andean Lakes above and below
      timberline: from community composition to community function.
AB  - Lakes located above the timberline are remote systems with a number of extreme
      environmental conditions, becoming physically harsh ecosystems, and sensors of
      global change. We analyze bacterial community composition and community-level
      physiological profiles in mountain lakes located in an altitude gradient in North
      Patagonian Andes below and above the timberline, together with dissolved organic
      carbon (DOC) characterization and consumption. Our results indicated a decrease
      in 71 % of DOC and 65 % in total dissolved phosphorus (TDP) concentration as well
      as in bacteria abundances along the altitude range (1,380 to 1,950 m a.s.l.).
      Dissolved organic matter (DOM) fluorescence analysis revealed a low global
      variability composed by two humic-like components (allochthonous substances) and
      a single protein-like component (autochthonous substances). Lakes below the
      timberline showed the presence of all the three components, while lakes above the
      timberline the protein-like compound constituted the main DOC component.
      Furthermore, bacterial community composition similarity and ordination analysis
      showed that altitude and resource concentration (DOC and TDP) were the main
      variables determining the ordination of groups. Community-level physiological
      profiles showed a mismatch with bacteria community composition (BCC), indicating
      the absence of a relationship between genetic and functional diversity in the
      altitude gradient. However, carbon utilization efficiencies varied according to
      the presence of different compounds in DOM bulk. The obtained results suggest
      that the different bacterial communities in these mountain lakes seem to have
      similar metabolic pathways in order to be able to exploit the available DOC
      molecules.

PMID- 24863132
TI  - Baseline data of a population-based cohort of patients with diabetes in
      Switzerland (CoDiab-VD).
AB  - QUESTIONS UNDER STUDY: To describe a population-based sample of patients with
      diabetes and the quality of their care in the canton of Vaud, Switzerland, as a
      baseline measure for the evaluation of the "Programme cantonal Diabete". METHODS:
      We conducted a self-administered paper-based questionnaire survey. Non
      institutionalised adult (aged >=18 years) patients with diabetes diagnosed for at
      least 1 year and residing in the canton of Vaud were recruited by community
      pharmacies. Women with gestational diabetes, people with obvious cognitive
      impairment or people not sufficiently fluent in French were excluded. Primary
      outcomes were recommended processes-of-care and outcomes of care (glycosylated
      haemoglobin [HbA1c], generic and disease-specific health-related quality of life
      (HRQoL), overall care score in relation to the Chronic Care Model). Other
      measures included diabetes education, self-management support and self-efficacy,
      health status, health behaviour and demographics. RESULTS: A total of 519
      patients with diabetes were included. Whereas the mean HbA1c level was 7.3% (n =
      177, 95% confidence interval 7.1-7.5), diabetes-specific processes-of-care and
      influenza vaccination were reported by less than two-thirds of the patients.
      Physical activity and diet recommendations results mirrored patients'
      difficulties with their management in daily life and diabetes-specific HRQoL was
      worst in the dimensions relative to diet (eating and drinking) and sex life. A
      minority of patients reported ever having participated in diabetes education
      courses (32.8%). Overall, patients were satisfied with their care and the support
      they received. CONCLUSIONS: This study provides a broad picture of the
      experiences of people living with diabetes in the canton of Vaud. It shall guide
      the development of targeted interventions within the "Programme cantonal
      Diabete".

PMID- 24863133
TI  - The Sharvard Corpus: a phonemically-balanced Spanish sentence resource for
      audiology.
AB  - OBJECTIVE: The current study describes the collection of a new phonemically
      balanced Spanish sentence resource, known as the Sharvard Corpus. DESIGN: The
      resource contains 700 sentences inspired by the original English Harvard
      sentences along with speech recordings from a male and female native peninsular
      Spanish talker. Sentences each contain five keywords for scoring and are grouped
      into 70 lists of 10 sentences using an automatic phoneme-balancing procedure.
      STUDY SAMPLE: Twenty-three native Spanish listeners identified keywords in the
      Sharvard sentences in speech-shaped noise. RESULTS: Psychometric functions for
      the Sharvard sentences indicate mean speech reception thresholds of -6.07 and 
      6.24 dB, and slopes of 10.53 and 11.03 percentage points per dB at the 50%
      keywords correct point for male and female talkers respectively. CONCLUSIONS: The
      resulting open source collection of Spanish sentence material for speech
      perception testing is available online.

PMID- 24863134
TI  - Diagnostic yield and cost-effectiveness of investigations in patients presenting
      with isolated lower motor neuron signs.
AB  - Our objective was to investigate the yield and cost-effectiveness of
      investigations and therapeutic trials of intravenous immunoglobulin (IVIg) in
      patients presenting with isolated lower motor neuron (LMN) signs. We performed a
      retrospective chart review of cases diagnosed between January 2007 and September
      2013. Investigation results and their impact on outcome, and outcome of IVIg
      treatment trials were abstracted. Cost was calculated in Canadian dollars (C$).
      Fifty-nine of 333 patients presented with isolated LMN signs. The majority of
      patients (61%) evolved to amyotrophic lateral sclerosis (ALS) within 36 months of
      presentation, while 37.3% remained with progressive muscular atrophy (PMA) with
      mean follow-up 29.6 months. Of the 1210 tests performed, 4.9% were abnormal. The
      diagnosis was changed in only one patient where a muscle biopsy revealed a distal
      myopathy. Fourteen patients received therapeutic trials of IVIg to rule out an
      IVIg-responsive inflammatory motor neuropathy with no objective clinical benefit.
      Total group cost was C$630,484.72 (C$10,686.18/patient). IVIg represented 58.7%
      of total costs. In conclusion, extensive investigations and treatment trials of
      IVIg have low yield in the work-up of patients with isolated LMN signs and are
      not cost-effective when clinical features do not suggest an alternative diagnosis
      to PMA.

PMID- 24863135
TI  - Endoplasmic reticulum stress induces epithelial-mesenchymal transition through
      autophagy via activation of c-Src kinase.
AB  - BACKGROUND: Endoplasmic reticulum (ER) stress has been implicated in inducing
      epithelial-mesenchymal transition (EMT). ER stress is also known to induce
      autophagy. However, it is unclear whether ER stress-induced autophagy contributes
      to EMT. We hypothesized that ER stress might induce EMT through autophagy via
      activation of c-Src kinase in tubular epithelial cells. METHOD: All experiments
      were performed using HK-2 cells. Protein expression was measured by Western blot
      analysis. Immunofluorescence and small interfering RNA (siRNA) experiments were
      performed. RESULTS: Chemical ER stress inducers such as tunicamycin (TM, 0.2 MUM)
      and thapsigargin (TG, 0.2 MUM) induced EMT, as shown by upregulation of alpha
      smooth muscle actin and downregulation of E-cadherin. ER stress inhibitors such
      as 4-PBA and salubrinal suppressed both TM- and TG-induced EMT. TM and TG also
      induced autophagy, as evidenced by upregulation of LC3-II and beclin-1, which
      were abolished by pretreatment with ER stress inhibitors. Transfection with siRNA
      targeting ER stress protein (IRE-1) blocked the TM- or TG-induced EMT and
      autophagy. Autophagy inhibitors such as 3-methyladenine and bafilomycin inhibited
      the TM- or TG-induced EMT. Transfection with siRNA targeting autophagy protein
      (beclin-1) also blocked the TM- or TG-induced EMT. Both TM and TG induced
      activation of c-Src kinase. Inhibitor of c-Src kinase (PP2) suppressed the TM- or
      TG-induced autophagy and EMT. CONCLUSION: ER stress by TM or TG induced EMT
      through autophagy via activation of c-Src kinase in tubular epithelial cells.

PMID- 24863136
TI  - Methoxypyrazine composition of Coccinellidae-tainted Riesling and Pinot noir wine
      from Germany.
AB  - BACKGROUND: Harmonia axyridis (multicolored Asian ladybeetle) and Coccinella
      septempunctata (seven-spot ladybeetle) (Coccinellidae) are found in many wine
      regions in Europe and the Americas, where they are responsible for a pronounced
      wine fault known as 'ladybug taint' when incorporated with grapes during harvest
      operations. Methoxypyrazines have been proposed in the literature as the
      compounds responsible for the taint. This study sought to expand on this
      identification and also determine the effectiveness of heating Coccinellidae
      affected grape must prior to fermentation as a possible remedial intervention.
      Riesling and Pinot noir grapes were infested with H. axyridis or C.
      septempunctata at different densities and fermented to dryness. The Pinot noir
      was either must heated prior to fermentation or processed without heating
      (control). All wines were analyzed for 2-isopropyl-, 2-sec-butyl-, 2-isobutyl-
      and 2,5-dimethyl-3-methoxypyrazine using headspace solid phase
      microextraction/multidimensional gas chromatography/mass spectrometry. RESULTS:
      Concentrations of 2-isopropyl-3-methoxypyrazine increased with beetle density for
      both Coccinellidae species, while other methoxypyrazines showed inconsistent or
      no variation with infestations levels. Heating of Pinot noir grapes prior to
      fermentation resulted in a moderate decrease in all methoxypyrazines. CONCLUSION:
      These results provide direction for more targeted treatments aimed at remediating
      musts/wines affected by Coccinellidae and indicate that winegrowers do not need
      to differentiate between H. axyridis and C. septempunctata when making action
      threshold decisions in the vineyard or winery.

PMID- 24863137
TI  - Medical service redesign shares the load saving 6000 bed days and improving
      morale.
AB  - BACKGROUND AND AIMS: In 2010, demand on the Auckland City Hospital general
      medical service exceeded capacity. A review by the Royal Australasian College of
      Physicians was critical of training offered to registered medical officers, and
      low morale was a problem across the service. Management offered support for an
      improved model that would solve these problems. METHODS: A project to redesign
      the general medical service was undertaken. Baseline analysis found uneven
      workload and insufficient capacity at peak times for patient presentations.
      Workshops involving the entire service led to a new model that splits workload
      and teams into patients likely to have a short stay from those requiring longer,
      ward-based care. Admissions are now distributed over 12 teams on weekdays and 4
      on the weekends. There was an increase of approximately 2.5 in consultant full
      time equivalents but no change in registrar or house officer staffing. RESULTS:
      Since the introduction of the new model, the average length of stay has fallen
      from 3.7 to 3.2 days (14%) and the median length of stay by 28%, resulting in a
      saving of 6000 bed days per year. Readmission, inpatient and 30-day mortality
      rates are unchanged. These results have been sustained over 18 months with signs
      of continuing improvement. CONCLUSION: This project owes its success to the
      following factors - management support; iterative engagement of a range of staff;
      provision of timely data analysis; increases in senior medical officer staffing
      and reorganisation leading to more predictable and fair work practices. One
      challenge is discontinuity, whether between doctors and patients or within the
      medical team.

PMID- 24863138
TI  - Analysis of particle-borne odorants emitted from concentrated animal feeding
      operations.
AB  - Airborne particles are known to serve as a carrier of odors emanating from
      concentrated animal feeding operations (CAFOs). However, limited quantitative
      data about particle-borne odorants preclude an accurate assessment of the role of
      particles in odor transport. This study collected total suspended particulates
      (TSP) and PM10 (particles with aerodynamic diameter smaller than 10 MUm) at the
      air exhaust of eight types of CAFOs (swine: farrowing, gestation, weaning, and
      finishing; poultry: manure-belt layer hen, tom turkey, chicken broiler, and cage
      free layer hen; in total 20 animal buildings) in multiple seasons, and examined
      the variability in particle odorant composition with animal operation type,
      season, and particle size. Fifty-seven non-sulfur-containing odorants were
      identified and quantitated, including carbonyls, alcohols, acids, phenols, and
      nitrogen-containing compounds. They in total accounted for 2.19+/-1.52% TSP and
      4.97+/-3.25% PM10 mass. Acetic acid and ethanol were most abundant but less odor
      contributing than phenylacetic acid, indole, dodecanoic acid, and (E,E)-2,4
      decadienal, as determined by odor activity value. Particle odorant composition
      varied significantly with animal operation type, season, and particle size. The
      TSP and PM10 samples from swine gestation buildings, for example, showed
      distinctly different odorant compositions than those from tom turkey buildings.
      The summer TSP and PM10 samples contained in general lower concentrations of
      short-chain fatty acids but higher concentrations of long-chain fatty acids,
      aldehydes, and short-chain alcohols than the winter samples. Compared to TSP,
      PM10 samples from different types of CAFOs shared a more similar odorant
      composition, contained higher odorant concentrations per mass of particles, and
      accounted for on average 53.2% of the odor strength of their corresponding TSP
      samples.

PMID- 24863139
TI  - Evaluating the critical source area concept of phosphorus loss from soils to
      water-bodies in agricultural catchments.
AB  - Using data collected from six basins located across two hydrologically
      contrasting agricultural catchments, this study investigated whether transport
      metrics alone provide better estimates of storm phosphorus (P) loss from basins
      than critical source area (CSA) metrics which combine source factors as well.
      Concentrations and loads of P in quickflow (QF) were measured at basin outlets
      during four storm events and were compared with dynamic (QF magnitude) and static
      (extent of highly-connected, poorly-drained soils) transport metrics and a CSA
      metric (extent of highly-connected, poorly-drained soils with excess plant
      available P). Pairwise comparisons between basins with similar CSA risks but
      contrasting QF magnitudes showed that QF flow-weighted mean TRP (total molybdate
      reactive P) concentrations and loads were frequently (at least 11 of 14
      comparisons) more than 40% higher in basins with the highest QF magnitudes.
      Furthermore, static transport metrics reliably discerned relative QF magnitudes
      between these basins. However, particulate P (PP) concentrations were often (6 of
      14 comparisons) higher in basins with the lowest QF magnitudes, most likely due
      to soil-management activities (e.g. ploughing), in these predominantly arable
      basins at these times. Pairwise comparisons between basins with contrasting CSA
      risks and similar QF magnitudes showed that TRP and PP concentrations and loads
      did not reflect trends in CSA risk or QF magnitude. Static transport metrics did
      not discern relative QF magnitudes between these basins. In basins with
      contrasting transport risks, storm TRP concentrations and loads were well
      differentiated by dynamic or static transport metrics alone, regardless of
      differences in soil P. In basins with similar transport risks, dynamic transport
      metrics and P source information additional to soil P may be required to predict
      relative storm TRP concentrations and loads. Regardless of differences in
      transport risk, information on land use and management, may be required to
      predict relative differences in storm PP concentrations between these
      agricultural basins. 

PMID- 24863141
TI  - The role of vitamin supplementation in the prevention of cardiovascular disease
      events.
AB  - The production, sale, and consumption of multiple vitamins is a multibillion
      dollar industry. Most Americans take some form of supplement ostensibly for
      prevention of cardiovascular disease. It has been claimed that vitamin A retards
      atherogenesis. Vitamin C is an antioxidant and is thought to possibly decrease
      free radical-induced endothelial injury, which can lead to atherosclerotic plaque
      formation. Vitamin E has been extensively studied for its possible effects on
      platelet function as well as inhibition of foam-cell formation. Low levels of
      vitamin D have been thought to negatively impact myocardial structure and
      increase the risk for cardiovascular events. Increased intake of vitamin B6, B12,
      and folate has been associated with reduction of homocysteine levels; elevated
      homocysteine blood levels have been associated with the occurrence of stroke,
      heart attack, and cardiovascular death. The purpose of this study was to review
      the currently available literature for vitamin supplementation with respect to
      prevention of cardiovascular disease. Unfortunately, the current evidence
      suggests no benefit exists with vitamin supplementation in the general US
      population. Further research is needed to evaluate whether there are specific
      populations that might benefit from vitamin supplementation. 

PMID- 24863140
TI  - Persistent migraine aura: new cases, a literature review, and ideas about
      pathophysiology.
AB  - BACKGROUND: Persistent migraine aura without infarction (PMA) is a rare condition
      that is defined as an aura that lasts longer than 1 week in absence of
      infarction. Two types of PMA have been distinguished, notably persistent primary
      visual disturbance (PPVD) and typical aura (TA). OBJECTIVES: This case-based
      review article describes four new cases of PMA as well as reviews all cases
      reported, trying to identify relevant associations, in particular with respect to
      functional investigations. METHODS: We performed a systematic literature search,
      extending from the period when it was first described (1991) to March 2014. We
      included all case descriptions of which criteria for PMA formulated in the
      International Classification of Headache Disorders, second edition, were met. In
      addition, we described four new cases. RESULTS: We identified 47 cases of PMA, 27
      PMA-PPVD and 19 PMA-TA. In one case, there was not enough information to define
      the type of PMA. The mean age of onset was 30 years, varying from 7 to 74 years.
      The duration of symptoms varied from 9 days to 28 years. Besides a longer
      duration in symptoms in the PMA-PPVD group, we could not identify any differences
      between these groups. Some authors report occipital hypoactivity on Tc99m
      hexamethylpropylene amine oxime -single-photon emission computed tomography
      (Tc99m-HMPAO-SPECT) or fluorodeoxyglucose-positron emission tomography (FDG-PET)
      in PMA cases, but data are inconsistent. Multiple drugs have been used for the
      treatment of PMA, usually with little effect. Lamotrigine seems to be the most
      effective drug. CONCLUSION: Despite the fact that 47 cases of PMA have been
      reviewed in this paper, many questions remain. The cases that have been described
      so far show inconsistent data with respect to the results of functional studies
      as well as treatment effects. The pathophysiology of PMA is still largely a
      matter of conjecture.

PMID- 24863142
TI  - Fungemia and interstitial lung compromise caused by Malassezia sympodialis in a
      pediatric patient.
AB  - A case of fungemia with interstitial lung compromise caused by Malassezia
      sympodialis is reported in an obese pediatric patient on long-term treatment with
      inhaled corticosteroids for asthma. The patient was hospitalized due to a post
      surgical complication of appendicitis. The patient was treated with amphotericin
      B for 3 weeks, with good clinical evolution and subsequent negative cultures. 

PMID- 24863143
TI  - Cognitive behavior therapy-based psychoeducational groups for adults with ADHD
      and their significant others (PEGASUS): an open clinical feasibility trial.
AB  - The aim of this pilot study was to investigate the feasibility and effectiveness
      of a new psychoeducative intervention program (PEGASUS) for adults with ADHD and
      their significant others in a psychiatric outpatient context. At three outpatient
      psychiatric clinics, adults with ADHD and their significant others took part in
      PEGASUS, a psychoeducational program based on theories from cognitive behavioral
      therapy, neuropsychology, and cross-disciplinary evidence regarding ADHD. In
      total, 108 adults were allocated to treatment (51 with ADHD and their 57
      significant others). Feasibility was evaluated regarding suitability of the
      intervention at a psychiatric outpatient clinic and treatment completion.
      Preliminary efficacy was evaluated per protocol from baseline to post
      intervention (n = 41 adults with ADHD and 40 significant others). In a
      feasibility analysis, the intervention was judged to be a suitable treatment
      option for 94.5 % of all individuals with a primary diagnosis of ADHD at an
      outpatient psychiatric clinic. In total, 43 out of 51 allocated individuals with
      ADHD (84.3 %) completed the intervention. The corresponding figures for their
      significant others were 42 out of 57 (73.7 %). Knowledge about ADHD increased,
      and both the quality of relationships and psychological well-being improved from
      baseline to post-intervention in all participants. The significant others
      reported a reduction in the subjective burden of care, such as worry and guilt.
      The objective burden of care (such as financial problems) did not change. The
      findings support the potential value of psychoeducation for adults with ADHD and
      their significant others. An ongoing randomized controlled trial will generate
      further evidence concerning the PEGASUS program. 

PMID- 24863145
TI  - FTO genotype and aging: pleiotropic longitudinal effects on adiposity, brain
      function, impulsivity and diet.
AB  - Although overweight and obesity are associated with poor health outcomes in the
      elderly, the biological bases of obesity-related behaviors during aging are
      poorly understood. Common variants in the FTO gene are associated with adiposity
      in children and younger adults as well as with adverse mental health in older
      individuals. However, it is unclear whether FTO influences longitudinal
      trajectories of adiposity and other intermediate phenotypes relevant to mental
      health during aging. We examined whether a commonly carried obesity-risk variant
      in the FTO gene (rs1421085 single-nucleotide polymorphism) influences adiposity
      and is associated with changes in brain function in participants within the
      Baltimore Longitudinal Study of Aging, one of the longest-running longitudinal
      aging studies in the United States. Our results show that obesity-related risk
      allele carriers of FTO gene show dose-dependent increments in body mass index
      during aging. Moreover, the obesity-related risk allele is associated with
      reduced medial prefrontal cortical function during aging. Consistent with reduced
      brain function in regions intrinsic to impulse control and taste responsiveness,
      risk allele carriers of FTO exhibit dose-dependent increments in both impulsivity
      and intake of fatty foods. We propose that a common neural mechanism may underlie
      obesity-associated impulsivity and increased consumption of high-calorie foods
      during aging. 

PMID- 24863146
TI  - Role of the vasopressin 1b receptor in rodent aggressive behavior and synaptic
      plasticity in hippocampal area CA2.
AB  - The vasopressin 1b receptor (Avpr1b) is critical for social memory and social
      aggression in rodents, yet little is known about its specific roles in these
      behaviors. Some clues to Avpr1b function can be gained from its profile of
      expression in the brain, which is largely limited to the pyramidal neurons of the
      CA2 region of the hippocampus, and from experiments showing that inactivation of
      the gene or antagonism of the receptor leads to a reduction in social aggression.
      Here we show that partial replacement of the Avpr1b through lentiviral delivery
      into the dorsal CA2 region restored the probability of socially motivated attack
      behavior in total Avpr1b knockout mice, without altering anxiety-like behaviors.
      To further explore the role of the Avpr1b in this hippocampal region, we examined
      the effects of Avpr1b agonists on pyramidal neurons in mouse and rat hippocampal
      slices. We found that selective Avpr1b agonists induced significant potentiation
      of excitatory synaptic responses in CA2, but not in CA1 or in slices from Avpr1b
      knockout mice. In a way that is mechanistically very similar to synaptic
      potentiation induced by oxytocin, Avpr1b agonist-induced potentiation of CA2
      synapses relies on NMDA (N-methyl-D-aspartic acid) receptor activation, calcium
      and calcium/calmodulin-dependent protein kinase II activity, but not on cAMP
      dependent protein kinase activity or presynaptic mechanisms. Our data indicate
      that the hippocampal CA2 is important for attacking in response to a male
      intruder and that the Avpr1b, likely through its role in regulating CA2 synaptic
      plasticity, is a necessary mediator. 

PMID- 24863150
TI  - Cohesive-energy-resolved bandgap of nanoscale graphene derivatives.
AB  - With a size-dependent cohesive energy formula for two-dimensional coordinated
      materials, the bandgap variation in quantum dots and nanoribbons of graphene
      derivatives, such as graphane, fluorographene and graphene oxides, is
      investigated. The bandgap is found to increase substantially as the diameter or
      width of the nano-sized material decreases. The bandgap variation is attributed
      to the change in cohesive energy of edge carbon atoms, and is associated with the
      physicochemical nature and degree of edge saturation. These predictions agree
      with previously reported computer simulation results, and have potential
      application in wide-band optics and optoelectronics. 

PMID- 24863147
TI  - Evolutionarily conserved prefrontal-amygdalar dysfunction in early-life anxiety.
AB  - Some individuals are endowed with a biology that renders them more reactive to
      novelty and potential threat. When extreme, this anxious temperament (AT) confers
      elevated risk for the development of anxiety, depression and substance abuse.
      These disorders are highly prevalent, debilitating and can be challenging to
      treat. The high-risk AT phenotype is expressed similarly in children and young
      monkeys and mechanistic work demonstrates that the central (Ce) nucleus of the
      amygdala is an important substrate. Although it is widely believed that the flow
      of information across the structural network connecting the Ce nucleus to other
      brain regions underlies primates' capacity for flexibly regulating anxiety, the
      functional architecture of this network has remained poorly understood. Here we
      used functional magnetic resonance imaging (fMRI) in anesthetized young monkeys
      and quietly resting children with anxiety disorders to identify an evolutionarily
      conserved pattern of functional connectivity relevant to early-life anxiety.
      Across primate species and levels of awareness, reduced functional connectivity
      between the dorsolateral prefrontal cortex, a region thought to play a central
      role in the control of cognition and emotion, and the Ce nucleus was associated
      with increased anxiety assessed outside the scanner. Importantly, high-resolution
      18-fluorodeoxyglucose positron emission tomography imaging provided evidence that
      elevated Ce nucleus metabolism statistically mediates the association between
      prefrontal-amygdalar connectivity and elevated anxiety. These results provide new
      clues about the brain network underlying extreme early-life anxiety and set the
      stage for mechanistic work aimed at developing improved interventions for
      pediatric anxiety. 

PMID- 24863149
TI  - Decreased gamma-aminobutyric acid levels in the parietal region of patients with
      Alzheimer's disease.
AB  - PURPOSE: To determine whether there are in vivo differences of gamma-aminobutyric
      acid (GABA) levels in frontal and parietal regions of Alzheimer's disease (AD)
      patients, compared with healthy controls using magnetic resonance spectroscopy
      ((1) H-MRS). MATERIALS AND METHODS: Fifteen AD patients and fifteen age- and
      gender-matched healthy controls underwent (1) H-MRS of the frontal and parietal
      lobes using the "MEGA-Point Resolved Spectroscopy Sequence" (MEGA-PRESS)
      technique, and cognitive levels of subjects were evaluated using Mini-Mental
      State Examination (MMSE) tests. MRS data were processed using the Gannet program.
      Because the signal detected by MEGA-PRESS includes contributions from GABA,
      macromolecules and homocarnosine, it is labeled as "GABA+" rather than GABA.
      Differences of GABA+/Cr ratios between AD patients and controls were tested using
      covariance analysis, adjusting for gray matter fraction. The relationship between
      GABA+/Cr and MMSE scores was also analyzed. RESULTS: Significant lower GABA+/Cr
      ratios were found in the parietal region of AD patients compared with controls (P
      = 0.041). In AD patients, no significant correlations between GABA+/Cr and MMSE
      scores were found in either the frontal (r = -0.164; P = 0.558) or parietal
      regions (r = 0.025; P = 0.929). CONCLUSION: Decreased GABA+/Cr levels were
      present in the parietal region of patients with AD in vivo, suggesting that
      abnormalities of the GABAergic system may be present in the pathogenesis of AD.

PMID- 24863148
TI  - Maternal use of antidepressant or anxiolytic medication during pregnancy and
      childhood neurodevelopmental outcomes: a systematic review.
AB  - Antidepressant and anxiolytic medications are widely prescribed and used by
      pregnant women for acute and maintenance therapy. These drugs are able to pass
      the placental barrier, and may potentially influence fetal and brain development.
      It is possible that exposure to prenatal antidepressants or anxiolytic medication
      may disturb neurotransmitter systems in the brain and have long-lasting
      consequences on neurodevelopment in the offspring. As all medication during
      pregnancy may pose a certain risk to the developing fetus, the potential benefits
      of the medication must be weighed against the risks for both mother and her
      unborn child. Therefore, information to guide patients and physicians to make a
      well-balanced decision for the appropriate treatment during pregnancy is needed.
      In this systematic review, an overview of maternal use of antidepressant or
      anxiolytic medication during pregnancy and childhood neurodevelopmental outcomes
      is provided. Some studies indicate a relation between prenatal exposure to
      antidepressants and adverse neurodevelopmental outcomes such as delayed motor
      development/motor control, social difficulties, internalizing problems and
      autism, but cannot rule out confounding by indication. Overall, the results of
      the observational studies have been inconsistent, which makes translation of the
      findings into clinical recommendations difficult. More well-designed
      observational studies and also randomized controlled trials (e.g., maintenance
      treatment vs. cessation) are needed to move forward and provide a comprehensive
      evaluation of the risks and benefits of antidepressant and anxiolytic use during
      pregnancy. 

PMID- 24863151
TI  - Range-wide analysis of genetic structure in a widespread, highly mobile species
      (Odocoileus hemionus) reveals the importance of historical biogeography.
AB  - Highly mobile species that thrive in a wide range of habitats are expected to
      show little genetic differentiation across their range. A limited but growing
      number of studies have revealed that patterns of broad-scale genetic
      differentiation can and do emerge in vagile, continuously distributed species.
      However, these patterns are complex and often shaped by both historical and
      ecological factors. Comprehensive surveys of genetic variation at a broad scale
      and at high resolution are useful for detecting cryptic spatial genetic structure
      and for investigating the relative roles of historical and ecological processes
      in structuring widespread, highly mobile species. In this study, we analysed 10
      microsatellite loci from over 1900 samples collected across the full range of
      mule deer (Odocoileus hemionus), one of the most widely distributed and abundant
      of all large mammal species in North America. Through both individual- and
      population-based analyses, we found evidence for three main genetic lineages, one
      corresponding to the 'mule deer' morphological type and two to the 'black-tailed
      deer' type. Historical biogeographic events likely are the primary drivers of
      genetic divergence in this species; boundaries of the three lineages correspond
      well with predictions based on Pleistocene glacial cycles, and substructure
      within each lineage demonstrates island vicariance. However, across large
      geographic areas, including the entire mule deer lineage, we found that genetic
      variation fit an isolation-by-distance pattern rather than discrete clusters. A
      lack of genetic structure across wide geographic areas of the continental west
      indicates that ecological processes have not resulted in restrictions to gene
      flow sufficient for spatial genetic structure to emerge. Our results have
      important implications for our understanding of evolutionary mechanisms of
      divergence, as well as for taxonomy, conservation and management.

PMID- 24863153
TI  - Development and validation of a medical chart review checklist for symptom
      management performance of oncologists in the routine care of patients with
      advanced cancer.
AB  - CONTEXT: Oncologists perform a range of pharmacological and nonpharmacological
      interventions to manage the symptoms of outpatients with advanced cancer.
      OBJECTIVES: The aim of this study was to develop and test a symptom management
      performance checklist (SyMPeC) to review medical charts. METHODS: First, the
      content of the checklist was determined by consensus of an interprofessional
      team. The SyMPeC was tested using the data set of the SAKK 96/06 E-MOSAIC
      (Electronical Monitoring of Symptoms and Syndromes Associated with Cancer) trial,
      which included six consecutive visits from 247 patients. In a test data set (half
      of the data) of medical charts, two people extracted and quantified the
      definitions of the parameters (content validity). To assess the inter-rater
      reliability, three independent researchers used the SyMPeC on a random sample
      (10% of the test data set), and Fleiss's kappa was calculated. To test external
      validity, the interventions retrieved by the SyMPeC chart review were compared
      with nurse-led assessment of patient-perceived oncologists' palliative
      interventions. RESULTS: Five categories of symptoms were included: pain, fatigue,
      anorexia/nausea, dyspnea, and depression/anxiety. Interventions were categorized
      as symptom specific or symptom unspecific. In the test data set of 123 patients,
      402 unspecific and 299 symptom-specific pharmacological interventions were
      detected. Nonpharmacological interventions (n = 242) were mostly symptom
      unspecific. Fleiss's kappa for symptom and intervention detections was K = 0.7
      and K = 0.86, respectively. In 1003 of 1167 visits (86%), there was a match
      between SyMPeC and nurse-led assessment. Seventy-nine percent (195 of 247) of
      patients had no or one mismatch. CONCLUSION: Chart review by SyMPeC seems
      reliable to detect symptom management interventions by oncologists in outpatient
      clinics. Nonpharmacological interventions were less symptom specific. A template
      for documentation is needed for standardization.

PMID- 24863152
TI  - Strategies to support recruitment of patients with life-limiting illness for
      research: the Palliative Care Research Cooperative Group.
AB  - CONTEXT: The Palliative Care Research Cooperative Group (PCRC) is the first
      clinical trials cooperative for palliative care in the U.S. OBJECTIVES: To
      describe barriers and strategies for recruitment during the inaugural PCRC
      clinical trial. METHODS: The parent study was a multisite randomized controlled
      trial enrolling adults with life expectancy anticipated to be one to six months,
      randomized to discontinue statins (intervention) vs. to continue on statins
      (control). To study recruitment best practices, we conducted semistructured
      interviews with 18 site principal investigators (PIs) and clinical research
      coordinators (CRCs) and reviewed recruitment rates. Interviews covered three
      topics: 1) successful strategies for recruitment, 2) barriers to recruitment, and
      3) optimal roles of the PI and CRC. RESULTS: All eligible site PIs and CRCs
      completed interviews and provided data on statin protocol recruitment. The parent
      study completed recruitment of 381 patients. Site enrollment ranged from 1 to 109
      participants, with an average of 25 enrolled per site. Five major barriers
      included difficulty locating eligible patients, severity of illness, family and
      provider protectiveness, seeking patients in multiple settings, and lack of
      resources for recruitment activities. Five effective recruitment strategies
      included systematic screening of patient lists, thoughtful messaging to make
      research relevant, flexible protocols to accommodate patients' needs, support
      from clinical champions, and the additional resources of a trials cooperative
      group. CONCLUSION: The recruitment experience from the multisite PCRC yields new
      insights into methods for effective recruitment to palliative care clinical
      trials. These results will inform training materials for the PCRC and may assist
      other investigators in the field.

PMID- 24863154
TI  - Reduction of acute hospital admissions and improvement in outpatient attendance
      by intensified renal palliative care clinic follow-up: the Hong Kong experience.
AB  - BACKGROUND: End-stage renal failure patients often fail to attend scheduled renal
      palliative care clinic (RPCC) follow-up because of acute hospital admissions,
      causing negative impact on patients' well-being and health care burden. MEASURES:
      The rates of RPCC attendance, emergency department (ED) attendance, and acute
      hospital admission per patient from January 2013 to June 2013 were analyzed.
      INTERVENTION: Patients who had more than one ED visit within three months were
      invited to intensify their RPCC follow-up schedule for symptom assessment,
      medical advice, psychosocial-spiritual care, and social worker support in the
      subsequent three months. OUTCOMES: Nineteen patients were included. The rate of
      ED attendance (2.63 vs. 0.63, P < 0.007) and acute hospital admission (1.59 vs.
      0.58, P < 0.009) was reduced significantly after intensified follow-up. Clinic
      attendance rates improved from 56% to 85%. CONCLUSIONS/LESSONS LEARNED: Our pilot
      results suggested that intensifying RPCC follow-up minimized the utilization of
      acute medical services and improved outpatient attendance at RPCC.

PMID- 24863155
TI  - Integrating the biopsychosocial model into quality measures in palliative care: a
      case for improving the hospice item set.

PMID- 24863157
TI  - Neurocognitive mechanisms of learning to read: print tuning in beginning readers
      related to word-reading fluency and semantics but not phonology.
AB  - During reading acquisition children learn to recognize orthographic stimuli and
      link them to phonology and semantics. The present study investigated
      neurocognitive processes of learning to read after one year of schooling. We
      aimed to elucidate the cognitive processes underlying neural tuning for print
      that has been shown to play an important role for reading and dyslexia. A 128
      channel EEG was recorded while 68 (Swiss-)German monolingual first grade children
      (mean age: 7.6) performed a one-back task with different types of letter and
      false-font strings. Print tuning was indexed by the N1 difference in the ERPs
      between German words and false-font strings, while the N1 lexicality effect was
      indexed by the difference between German words and pseudowords. In addition, we
      measured reading fluency, rapid automatized naming, phonological awareness,
      auditory memory span, and vocabulary. After one year of formal reading
      instruction N1 print tuning was clearly present at the group level, and could be
      detected at the individual level in almost 90% of the children. The N1 lexicality
      effect, however, could not be reliably found. On the cognitive level, next to
      word-reading fluency, vocabulary was also associated with N1 print tuning, but
      not measures reflecting phonological processing. These results demonstrate the
      presence of print tuning in the first year of reading acquisition and its
      development at the individual level. Moreover, individual differences in print
      tuning are not only related to word-reading fluency, but also to semantic
      knowledge, indicating that at early stages of learning to read the top-down
      modulation of print tuning is semantic rather than phonological in nature. 

PMID- 24863156
TI  - Recruitment and screening for a randomized trial investigating Roux-en-Y gastric
      bypass versus intensive medical management for treatment of type 2 diabetes.
AB  - BACKGROUND: Large-scale randomized clinical trials are needed to assess the role
      of Roux-en-Y gastric bypass (RYGB) in treating patients with type 2 diabetes
      mellitus (T2DM). Recruitment challenges must be understood. METHODS: One hundred
      twenty participants were needed for a prospective randomized controlled trial
      investigating treatments for hyperglycemia and cardiovascular disease risk
      factors in patients with T2DM. The trial had two arms-intensive medical
      management plus a rigorous lifestyle intervention (LS/IMM) versus LS/IMM with
      RYGB. Medical inclusion criteria included glycosylated hemoglobin (HbA1c) >= 8.0
      % while under the care of a physician and body mass index (BMI) 30.0-39.9
      kg/m(2). Another inclusion criterion was expressed willingness to accept
      randomization and participate fully. Varied recruitment strategies were employed
      at four academic hospitals in the USA and Taiwan, including referrals, mass
      media, direct mail to patients drawn from a practice-based database, and direct
      mail to commercial mailing lists. RESULTS: Between February 2008 and December
      2011, 2,648 candidates were phone-screened and 240 were screened on site; 120
      participants were eventually randomized. Impediments included stringent medical
      inclusion criteria and a lack of equipoise (i.e., strong beliefs or preferences)
      among patients and their personal community-based physicians. To meet timeline
      requirements, the upper limit for BMI was increased from 34.9 to 39.9 kg/m(2) and
      an additional site was added. CONCLUSIONS: We successfully recruited 120
      participants with poorly controlled T2DM and mild to moderate obesity.
      Participants had to be willing to accept randomization to either surgical or
      nonsurgical treatments. Recruitment took 4 years.

PMID- 24863158
TI  - Testing concordance of instrumental variable effects in generalized linear models
      with application to Mendelian randomization.
AB  - Instrumental variable regression is one way to overcome unmeasured confounding
      and estimate causal effect in observational studies. Built on structural mean
      models, there has been considerable work recently developed for consistent
      estimation of causal relative risk and causal odds ratio. Such models can
      sometimes suffer from identification issues for weak instruments. This hampered
      the applicability of Mendelian randomization analysis in genetic epidemiology.
      When there are multiple genetic variants available as instrumental variables, and
      causal effect is defined in a generalized linear model in the presence of
      unmeasured confounders, we propose to test concordance between instrumental
      variable effects on the intermediate exposure and instrumental variable effects
      on the disease outcome, as a means to test the causal effect. We show that a
      class of generalized least squares estimators provide valid and consistent tests
      of causality. For causal effect of a continuous exposure on a dichotomous outcome
      in logistic models, the proposed estimators are shown to be asymptotically
      conservative. When the disease outcome is rare, such estimators are consistent
      because of the log-linear approximation of the logistic function. Optimality of
      such estimators relative to the well-known two-stage least squares estimator and
      the double-logistic structural mean model is further discussed.

PMID- 24863159
TI  - dLin52 is crucial for dE2F and dRBF mediated transcriptional regulation of pro
      apoptotic gene hid.
AB  - Drosophila lin52 (dlin52) is a member of Myb transcription regulator complex and
      it shows a dynamic pattern of expression in all Drosophila tissues. Myb complex
      functions to activate or repress transcription in a site-specific manner;
      however, the detailed mechanism is yet to be clearly understood. Members of the
      Drosophila melanogaster Myb-MuvB/dREAM complex have been known to regulate
      expression of a wide range of genes including those involved in regulating
      apoptosis. E2F and its corepressor RBF also belong to this complex and together
      they regulate expression of genes involved in cell cycle progression, apoptosis,
      differentiation, and development. In the present study, we examined whether the
      depletion of dlin52 in developing photoreceptor neurons results in enhanced
      apoptosis and disorganisation of the ommatidia. Strikingly, we found that dLin52
      is essential for transcriptional repression of the pro-apoptotic gene, hid;
      decrease in dlin52 levels led to dramatic induction of hid and apoptosis in eye
      antennal discs. Reduction of Rpd3 (HDAC1), another member of the dREAM complex,
      also led to marginal upregulation of Hid. In addition, we also demonstrated that
      an optimum level of dLin52 is needed for dE2F1/2 activity on the hid promoter.
      dlin52 cooperates with dRBF and dE2F1/2 for recruitment of repressor complex on
      the hid promoter. Preliminary data indicate that Rpd3/HDAC1 also contributes to
      hid repression. Based on the findings, we conclude that dLin52 functions as a co
      factor and modulates activity of members of dMyb/dREAM complex at hid promoter,
      thus regulating apoptosis by repressing this pro-apoptotic gene in the developing
      Drosophila eye. 

PMID- 24863161
TI  - Fluorescence tools to investigate riboswitch structural dynamics.
AB  - Riboswitches are novel regulatory elements that respond to cellular metabolites
      to control gene expression. They are constituted of highly conserved domains that
      have evolved to recognize specific metabolites. Such domains, so-called aptamers,
      are folded into intricate structures to enable metabolite recognition. Over the
      years, the development of ensemble and single-molecule fluorescence techniques
      has allowed to probe most of the mechanistic aspects of aptamer folding and
      ligand binding. In this review, we summarize the current fluorescence toolkit
      available to study riboswitch structural dynamics. We fist describe those methods
      based on fluorescent nucleotide analogues, mostly 2-aminopurine (2AP), to
      investigate short-range conformational changes, including some key steady-state
      and time-resolved examples that exemplify the versatility of fluorescent
      analogues as structural probes. The study of long-range structural changes by
      Forster resonance energy transfer (FRET) is mostly discussed in the context of
      single-molecule studies, including some recent developments based on the
      combination of single-molecule FRET techniques with controlled chemical
      denaturation methods. This article is part of a Special Issue entitled:
      Riboswitches.

PMID- 24863160
TI  - Common themes and differences in SAM recognition among SAM riboswitches.
AB  - The recent discovery of short cis-acting RNA elements termed riboswitches has
      caused a paradigm shift in our understanding of genetic regulatory mechanisms.
      The three distinct superfamilies of S-adenosyl-l-methionine (SAM) riboswitches
      are the most commonly found riboswitch classes in nature. These RNAs represent
      three independent evolutionary solutions to achieve specific SAM recognition.
      This review summarizes research on 1) modes of gene regulatory mechanisms, 2)
      common themes and differences in ligand recognition, and 3) ligand-induced
      conformational dynamics among SAM riboswitch families. The body of work on the
      SAM riboswitch families constitutes a useful primer to the topic of gene
      regulatory RNAs as a whole. This article is part of a Special Issue entitled:
      Riboswitches.

PMID- 24863163
TI  - Temperature-accelerated molecular dynamics gives insights into globular
      conformations sampled in the free state of the AC catalytic domain.
AB  - The catalytic domain of the adenyl cyclase (AC) toxin from Bordetella pertussis
      is activated by interaction with calmodulin (CaM), resulting in cAMP
      overproduction in the infected cell. In the X-ray crystallographic structure of
      the complex between AC and the C terminal lobe of CaM, the toxin displays a
      markedly elongated shape. As for the structure of the isolated protein,
      experimental results support the hypothesis that more globular conformations are
      sampled, but information at atomic resolution is still lacking. Here, we use
      temperature-accelerated molecular dynamics (TAMD) simulations to generate
      putative all-atom models of globular conformations sampled by CaM-free AC. As
      collective variables, we use centers of mass coordinates of groups of residues
      selected from the analysis of standard molecular dynamics (MD) simulations.
      Results show that TAMD allows extended conformational sampling and generates AC
      conformations that are more globular than in the complexed state. These
      structures are then refined via energy minimization and further unrestrained MD
      simulations to optimize inter-domain packing interactions, thus resulting in the
      identification of a set of hydrogen bonds present in the globular conformations.

PMID- 24863162
TI  - Long-term outcome of Guillain-Barre syndrome in children.
AB  - The objective of this study is to determine the long-term outcome and
      consequences of Guillain-Barre syndrome (GBS) in children. This is an
      observational cross-sectional cohort study of children diagnosed with GBS (0-18
      years old) at the Sophia Children's Hospital in Rotterdam from 1987 to 2009. All
      patients were invited for a structured interview, questionnaires, and full
      neurologic exam to record their current clinical condition focused on complaints
      and symptoms, neurological deficits, disabilities, behavior, and quality of life.
      Thirty-seven patients participated, 23 were now adults, with a median age of 20
      years (range 4-39 years) and a median follow-up time of 11 years (range 1-22
      years). Residual complaints were reported by 24 (65%) patients, including
      paresthesias (38%), unsteadiness of gait in the dark (37%), painful hands or feet
      (24%), and severe fatigue (22%). Four patients had severe neurological deficits,
      including facial diplegia and limb weakness. Two patients had had a recurrence of
      GBS. In 10 patients (26%), GBS had a negative impact on their school career.
      Questionnaires identified a wide range of behavioral problems. Quality of life
      was below normal on the subscale vitality, and above normal on the subscales
      social functioning and positive emotions in the adult group. Most children show
      good recovery of neurological deficits after GBS, but many have persisting long
      term residual complaints and symptoms that may lead to psychosocial problems
      interfering with participation in daily life.

PMID- 24863164
TI  - Regional data analysis of Candida non-albicans strains collected in United States
      medical sites over a 6-year period, 2006-2011.
AB  - Limited data are available on temporal and geographic variation of occurrence and
      antifungal resistance of non-C. albicans Candida species (non-CA-CSP) from the
      USA. The objective of this study was to evaluate the occurrence and antifungal
      resistance of 1694 isolates of non-CA-CSP collected during the period 2006-2011.
      Isolates were recovered in 33 hospitals located in four regions: Northcentral,
      North-east, South-east and West and tested using CLSI reference broth
      microdilution methods. Non-CA-CSP represented 55.6% of all Candida. C. glabrata
      was most predominant (39-42% of non-CA-CSP). Infections due to C. glabrata, C.
      krusei and C. dubliniensis increased over the 6 years. Anidulafungin (3.6%) and
      caspofungin (5.7%) resistance were prominent among C. glabrata from the North
      east and West regions respectively. Resistance to micafungin was detected in 2.0%
      and 2.9% of C. glabrata from the West and North-east regions respectively.
      Echinocandin resistance was low, except for C. dubliniensis. Azole resistance was
      most prominent among C. glabrata from the South-east (13.6% fluconazole R) and
      the West (18.0%). Cross-resistance among three tested azoles was observed in C.
      glabrata from all regions. Whereas differences in species distribution and
      antifungal R varied across geographic regions, there was little evidence of
      temporal increase in resistance to azoles or echinocandins in the monitored non
      CA-CSP. 

PMID- 24863165
TI  - Bladder cancer: accelerating MVAC.

PMID- 24863166
TI  - Paediatric oncology: triple therapy avoids need for radiation in children with
      ALL.

PMID- 24863167
TI  - Straightforward access to water-soluble unsymmetrical sulfoxanthene dyes:
      application to the preparation of far-red fluorescent dyes with large stokes'
      shifts.
AB  - An efficient synthesis of water-soluble unsymmetrical sulforhodamine/sulforhodol
      fluorophores containing a single julolidine fragment is presented. Owing to their
      valuable spectral properties in aqueous buffers, these dyes, especially those
      bearing a free aniline or phenol moiety, are valuable components of fluorogenic
      probes for a variety of biosensing applications. A further extension of this
      synthetic methodology to unusual phenols, namely 7-N,N-dialkylamino-4-hydroxy
      coumarins has enabled us to provide a new family water-soluble dyes of large
      Stokes' shift with far-red spectral features. 

PMID- 24863168
TI  - Quality of life after surgical resection compared with radiofrequency ablation
      for small hepatocellular carcinomas.
AB  - BACKGROUND: Health-related quality of life (HRQL) is an important outcome measure
      in studies of cancer therapy. This study aimed to investigate HRQL and survival
      in patients with small hepatocellular carcinoma (HCC) treated with either
      surgical resection or percutaneous radiofrequency ablation (RFA). METHODS:
      Between January 2006 and June 2009, patients with newly diagnosed solitary, small
      (3 cm or less) HCC were invited to participate in this non-randomized prospective
      parallel cohort study. The Functional Assessment of Cancer Therapy-Hepatobiliary
      (FACT-Hep) instrument was used for assessing HRQL. HRQL and survival were
      compared between the two treatment groups. RESULTS: A total of 389 patients were
      enrolled. Questionnaires were completed fully by 99.7 per cent of invited
      participants (388 of 389) at baseline, 98.7 per cent (383 of 388) at 3 months,
      99.0 per cent (379 of 383) at 6 months, 98.4 per cent (365 of 371) at 1 year,
      96.6 per cent (336 of 348) at 2 years and 95.1 per cent (289 of 304) at 3 years.
      There were no significant differences in disease-free and overall survival
      between the two groups. Patients treated with percutaneous RFA had significantly
      better HRQL total scores after 3, 6, 12, 24 and 36 months than those who had
      surgical resection (P < 0.001, P < 0.001, P = 0.001, P = 0.003 and P = 0.025
      respectively). On multivariable analysis, the presence of concomitant disease,
      cirrhosis and surgical resection were significant risk factors associated with a
      worse HRQL score after treatment. CONCLUSION: Percutaneous RFA produced better
      post-treatment HRQL than surgical resection for patients with solitary small (no
      more than 3 cm) HCC.

PMID- 24863169
TI  - What matters most? The content and concordance of patients' and providers'
      information priorities for contraceptive decision making.
AB  - OBJECTIVE(S): The objective of this study was to identify women's and health care
      providers' information priorities for contraceptive decision making and
      counseling, respectively. STUDY DESIGN: Cross-sectional surveys were administered
      online to convenience samples of 417 women and 188 contraceptive care providers
      residing in the United States. Participants were provided with a list of 34
      questions related to the features of contraceptive options and rated the
      importance of each. Participants also ranked the questions in descending order of
      importance. For both women and providers, we calculated the mean importance
      rating for each question and the proportion that ranked each question in their
      three most important questions. RESULTS: The average importance ratings given by
      women and providers were similar for 18 questions, but dissimilar for the
      remaining 16 questions. The question rated most important for women was "How does
      it work to prevent pregnancy?" whereas, for providers, "How often does a patient
      need to remember to use it?" and "How is it used?" were rated equally. The eight
      questions most frequently selected in the top three by women and/or providers
      were related to the safety of the method, mechanism of action, mode of use, side
      effects, typical- and perfect-use effectiveness, frequency of administration and
      when it begins to prevent pregnancy. CONCLUSION(S): Although we found
      considerable concordance between women's and provider's information priorities,
      the presence of some inconsistencies highlights the importance of patient
      centered contraceptive counseling and, in particular, shared contraceptive
      decision making. IMPLICATIONS: This study provides insights into the information
      priorities of women for their contraceptive decision making and health care
      providers for contraceptive counseling. These insights are critical both to
      inform the development of decision support tools for implementation in
      contraceptive care and to guide the delivery of patient-centered care.

PMID- 24863170
TI  - Determining the frequency, kinds and cues of violence displayed by patients in an
      acute older person ward environment: findings from an observational study.
AB  - BACKGROUND: Workplace violence is one of the most complex and significant
      occupational hazards experienced by nurses in healthcare settings. Verbal abuse
      and physical violence are particularly prevalent in older person assessment
      wards, owing to the prevalence of illnesses involving cognitive dysfunction; the
      high frequency and nature of contact with staff; and the frustration caused by
      high levels of disability. AIM: To determine the frequency, kinds and cues of
      violence displayed by patients towards nurses in an acute older person assessment
      ward environment using a structured observational tool - the Violence Assessment
      Tool (VAT). DESIGN: Observational study. METHOD: Non-participant structured
      observations of behavioural cues for violence towards nurses in an acute older
      person hospital ward were gathered and analysed. RESULTS: One hundred and twelve
      hours of observations were undertaken, resulting in 95 behavioural cues for
      violence in 19 patients. Four of these patients subsequently escalated to
      physical violence. Pacing around the bed was the only commonality in the
      behavioural cues of patients who became violent. All patients who became violent
      had previously demonstrated showing. CONCLUSIONS: To date, the assessment of
      potentially violent older patients has not been adequately addressed. The VAT may
      be one way of addressing this challenge through early identification of the more
      subtle behavioural cues that could indicate potential for violence. Further
      research on the VAT using a larger data set could determine its predictability
      for physically violent acts displayed by older people.

PMID- 24863171
TI  - A four-diode full-wave ionic current rectifier based on bipolar membranes:
      overcoming the limit of electrode capacity.
AB  - Full-wave rectification of ionic currents is obtained by constructing the typical
      four-diode bridge out of ion conducting bipolar membranes. Together with
      conjugated polymer electrodes addressed with alternating current, the bridge
      allows for generation of a controlled ionic direct current for extended periods
      of time without the production of toxic species or gas typically arising from
      electrode side-reactions. 

PMID- 24863173
TI  - Blood product recalls in the United States.
AB  - BACKGROUND: The blood recall process is intended to remove from use products that
      may be harmful, but characteristics of recalls nationally have not been reported.
      STUDY DESIGN AND METHODS: We analyzed recalls of all blood products for 2010 and
      categorized the reason for the recall, the organizations producing the recalled
      products, and the Food and Drug Administration (FDA) district in which the blood
      was collected. RESULTS: During 2010, there were 2468 recalls involving 8278 blood
      products. None of the recalls was considered to have a reasonable probability of
      causing serious adverse health consequences or death (FDA Class I). The most
      common reasons for recalls were donation and donor qualification (73%) and
      finished product quality control (14%). The FDA class of recalls varied by recall
      reason, month of the year, FDA district, number of units of blood collected per
      FDA district, and number of units of blood collected by the blood center. The
      number of recalls per 100,000 units of blood and the reason for recall varied by
      FDA district and blood centers collecting smaller numbers of units had more
      recalls. CONCLUSION: The absence of Class I recalls suggests a high level of
      quality and safety in the US blood supply. Organizations that collected larger
      numbers of units of blood had fewer recalls and there may be some FDA influences
      since the number and reason for the recalls varied by FDA district.

PMID- 24863172
TI  - Comparison of adrenocorticotropic hormone stimulation test results started 2
      versus 4 hours after trilostane administration in dogs with naturally occurring
      hyperadrenocorticism.
AB  - BACKGROUND: Trilostane medical treatment of naturally occurring
      hyperadrenocorticism (NOH) in dogs is common, as is use of the
      adrenocorticotropic hormone (ACTH) stimulation test (ACTHst) in monitoring
      response to treatment. There is uncertainty regarding when the ACTHst should be
      started relative to time of trilostane administration. OBJECTIVE: To compare
      ACTHst results in dogs being treated for NOH with trilostane when the test is
      begun 2 versus 4 hours after trilostane administration. ANIMALS: Twenty-one
      privately owned dogs with NOH, each treated with trilostane for at least 30 days.
      METHODS: Each dog had 2 ACTHst completed, 1 started 2 hours and the other 4 hours
      after trilostane administration. The second test was started no sooner than 46
      hours and no later than 74 hours after the first. RESULTS: For all 21 dogs, the
      mean post-ACTH serum cortisol concentration from tests started 2 hours after
      trilostane administration (5.4 +/- 3.7 MUg/dL) was significantly lower (P = .03)
      as compared with results from the tests started 4 hours after administration (6.5
      +/- 4.5 MUg/dL). CONCLUSIONS: Results of ACTHst started at different times yield
      significantly different results. Dogs with NOH, treated with trilostane, and
      monitored with ACTHst results should have all of their subsequent ACTHst tests
      begun at or about the same time after trilostane administration.

PMID- 24863175
TI  - Injectable in situ forming hybrid iron oxide-hyaluronic acid hydrogel for
      magnetic resonance imaging and drug delivery.
AB  - The development of multimodal in situ cross-linkable hyaluronic acid nanogels
      hybridized with iron oxide nanoparticles is reported. Utilizing a chemoselective
      hydrazone coupling reaction, the nanogels are converted to a macroscopic hybrid
      hydrogel without any additional reagent. Hydrophobic cargos remain encapsulated
      in the hydrophobic domains of the hybrid hydrogel without leakage. However,
      hydrogel degradation with hyaluronidase liberates iron oxide nanoparticles. This
      allows the utilization of imaging agents as tracers of the hydrogel degradation.
      UV-vis spectrometry and MRI studies reveal that the degradability of the
      hydrogels correlates with their structure. The hydrogels presented here are very
      promising theranostic tools for hyaluronidase-mediated delivery of hydrophobic
      drugs, as well as imaging of hydrogel degradation and tracking of degradation
      products in vivo. 

PMID- 24863176
TI  - Interaction of hydrophobic and amphipathic antimicrobial peptides with lipid
      bicelles.
AB  - Bicelles are model membrane systems that can be macroscopically oriented in a
      magnetic field at physiological temperature. The macroscopic orientation of
      bicelles allows to detect, by means of magnetic resonance spectroscopies, small
      changes in the order of the bilayer caused by solutes interacting with the
      membrane. These changes would be hardly detectable in isotropic systems such as
      vesicles or micelles. The aim of this work is to show that bicelles represent a
      convenient tool to investigate the behavior of antimicrobial peptides (AMPs)
      interacting with membranes, using electron paramagnetic resonance (EPR)
      spectroscopy. We performed the EPR experiments on spin-labeled bicelles using
      various AMPs of different length, charge, and amphipathicity: alamethicin,
      trichogin GA IV, magainin 2, HP(2-20), and HPA3. We evaluated the changes in the
      order parameter of the spin-labeled lipids as a function of the peptide-to-lipid
      ratio. We show that bicelles labeled at position 5 of the lipid chains are very
      sensitive to the perturbation induced by the AMPs even at low peptide
      concentrations. Our study indicates that peptides that are known to disrupt the
      membrane by different mechanisms (i.e., alamethicin vs magainin 2) show very
      distinct trends of the order parameter as a function of peptide concentration.
      Therefore, spin-labeled bicelles proved to be a good system to evaluate the
      membrane disruption mechanism of new AMPs.

PMID- 24863178
TI  - The roles of values, behavior, and value-behavior fit in the relation of agency
      and communion to well-being.
AB  - Four studies examined whether agency and communion values, behaviors, or an
      interaction between values and behaviors (value-behavior fit) would predict well
      being. In addition, Study 2 examined whether agency and communion goals,
      behaviors, or goal-behavior fit would predict well-being. In all four studies,
      participants completed online questionnaires containing measures of agency and
      communion values, behaviors, and well-being. In Studies 1 and 4, participants
      were recruited from the general population (respectively, N = 371, Mage  = 37.49,
      and N = 133, Mage  = 36.59). In Studies 2 and 3, participants were undergraduate
      students (respectively, N = 239, Mage  = 20.8, and N = 242, Mage  = 21.6). All
      four studies consistently found that agency and communion behaviors were
      significantly positively correlated with both subjective and psychological well
      being. There was no strong indication that either values were directly associated
      with well-being. Neither was there any indication that well-being was predicted
      by value-behavior fit. The implications of these findings for theory and
      improving well-being are discussed.

PMID- 24863177
TI  - Predictor factors for mortality in hybrid aortic procedures.

PMID- 24863179
TI  - Comparison of sulfate-reducing and conventional Anammox upflow anaerobic sludge
      blanket reactors.
AB  - Autotrophic NH4(+) removal has been extensively researched, but few studies have
      investigated alternative electron acceptors (for example, SO4(2-)) in NH4(+)
      oxidation. In this study, sulfate-reducing anaerobic ammonium oxidation (SRAO)
      and conventional Anammox were started up in upflow anaerobic sludge blanket
      reactors (UASBRs) at 36 (+/-0.5) degrees C and 20 (+/-0.5) degrees C
      respectively, using reject water as a source of NH4(+). SO4(2-) or NO2(-),
      respectively, were applied as electron acceptors. It was assumed that higher
      temperature could promote the SRAO, partly compensating its thermodynamic
      disadvantage comparing with the conventional Anammox to achieve comparable total
      nitrogen (TN) removal rate. Average volumetric NH4(+)-N removal rate in the
      sulfate-reducing UASBR1 was however 5-6 times less (0.03 kg-N/(m(3) day)) than in
      the UASBR2 performing conventional nitrite-dependent autotrophic nitrogen removal
      (0.17 kg-N/(m(3) day)). However, the stoichiometric ratio of NH4(+) removal in
      UASBR1 was significantly higher than could be expected from the extent of SO4(2-)
      reduction, possibly due to interactions between the N- and S-compounds and
      organic matter of the reject water. Injections of N2H4 and NH2OH accelerated the
      SRAO. Similar effect was observed in batch tests with anthraquinone-2,6
      disulfonate (AQDS). For detection of key microorganisms PCR-DGGE was used. From
      both UASBRs, uncultured bacterium clone ATB-KS-1929 belonging to the order
      Verrucomicrobiales, Anammox bacteria (uncultured Planctomycete clone Pla_PO55-9)
      and aerobic ammonium-oxidizing bacteria (uncultured sludge bacterium clone ASB08
      "Nitrosomonas") were detected. Nevertheless the SRAO process was shown to be less
      effective for the treatment of reject water, compared to the conventional
      Anammox. 

PMID- 24863180
TI  - Characterization of a pyridoxal-5'-phosphate-dependent l-lysine
      decarboxylase/oxidase from Burkholderia sp. AIU 395.
AB  - A novel enzyme, which catalyzed decarboxylation of l-lysine into cadaverine with
      release of carbon dioxide and oxidative deamination of l-lysine into l-2
      aminoadipic 5-semialdehyde with release of ammonia and hydrogen peroxide, was
      found from a newly isolated Burkholderia sp. AIU 395. The enzyme was specific to
      l-lysine and did not exhibit enzyme activities for other l-amino acids, l-lysine
      derivatives, d-amino acids, and amines. The apparent Km values for l-lysine in
      the oxidation and decarboxylation reactions were estimated to be 0.44 mM and 0.84
      mM, respectively. The molecular mass was estimated to be 150 kDa, which was
      composed of two identical subunits with molecular mass of 76.5 kDa. The enzyme
      contained one mol of pyridoxal 5'-phosphate per subunit as a prosthetic group.
      The enzyme exhibiting decarboxylase and oxidase activities for l-lysine was first
      reported here, while the deduced amino acid sequence was homologous to that of
      putative lysine decarboxylases from the genus Burkholderia. 

PMID- 24863182
TI  - Maximum information entropy: a foundation for ecological theory.
AB  - The maximum information entropy (MaxEnt) principle is a successful method of
      statistical inference that has recently been applied to ecology. Here, we show
      how MaxEnt can accurately predict patterns such as species-area relationships
      (SARs) and abundance distributions in macroecology and be a foundation for
      ecological theory. We discuss the conceptual foundation of the principle, why it
      often produces accurate predictions of probability distributions in science
      despite not incorporating explicit mechanisms, and how mismatches between
      predictions and data can shed light on driving mechanisms in ecology. We also
      review possible future extensions of the maximum entropy theory of ecology
      (METE), a potentially important foundation for future developments in ecological
      theory.

PMID- 24863181
TI  - Antioxidant and antityrosinase proanthocyanidins from Polyalthia longifolia
      leaves.
AB  - In the present study the structure of proanthocyanidins from Polyalthia
      longifolia leaves was characterized with (13)C nuclear magnetic resonance, high
      performance liquid chromatography electrospray ionization mass spectrometry, and
      matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
      analyses. The results showed that the proanthocyanidins were mixture of
      homopolymers of B-type procyanidins with degree of polymerization up to 14-mer.
      Furthermore, the antioxidant activity of the proanthocyanidins was studied
      through 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azino-bis(3-ethylbenzothiazoline-6
      sulphonic acid) free-radical scavenging activities, and ferric
      reducing/antioxidant power assays. In addition, antityrosinase activity of the
      proanthocyanidins was investigated. The IC50 for 2,2-diphenyl-1-picrylhydrazyl
      and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) free-radical
      scavenging activity of the proanthocyanidins were 89.32 +/- 12.07 and 76.79 +/-
      5.88 MUg/mL, respectively; the ferric reducing/antioxidant power value was 710.54
      +/- 142.82 mg ascorbic acid equivalent/g dry weight. The IC50 for antityrosinase
      activity was 773.09 +/- 1.47 MUg/mL. In conclusion, the proanthocyanidins from P.
      longifolia leaves exhibited potent antioxidant and antityrosinase activities.
      This research would provide scientific evidence for the use of proanthocyanidins
      from P. longifolia leaves as antioxidant and antityrosinase agents. 

PMID- 24863183
TI  - Endovascular repair of a thoracic aortic aneurysm in pregnancy at 22 weeks of
      gestation.
AB  - Thoracic aortic aneurysm is a rare condition that carries a critical risk of
      rupture and mortality. These risks are increased during pregnancy because of a
      progressively hyperdynamic pattern of circulation. Simultaneously, pregnancy
      imposed limitations on the use of ionized radiation and intravenous contrast
      agents may render conventional techniques for imaging and repair confirmation
      less acceptable. We describe a novel approach to intraoperative management of an
      endovascular repair for symptomatic thoracic saccular aneurysm in a pregnant
      patient, based on intravascular ultrasound and transesophageal echocardiography,
      with maintenance of uterine perfusion. The patient recovered well and proceeded
      to a normal delivery. Despite a favorable outcome in this case, further studies
      of perioperative management of aortic disease in pregnancy are needed. 

PMID- 24863184
TI  - Involvement of luminal nitric oxide in the pathogenesis of the gastroesophageal
      reflux disease spectrum.
AB  - Over the last 3 decades, the incidence of esophageal adenocarcinoma has
      dramatically increased in Western countries; a similar increase may be observed
      in Asian countries in the near future. Esophageal adenocarcinoma arises from a
      sequential gastroesophageal reflux disease (GERD) spectrum from reflux erosive
      esophagitis, to Barrett's esophagus, and finally to esophageal adenocarcinoma. At
      present, gastric acid and bile are assumed to be primarily involved in the
      etiology of the GERD spectrum. We reported in 2002 that, at the gastroesophageal
      junction in humans, abundant amounts of nitric oxide (NO) are generated luminally
      through the entero-salivary re-circulation of dietary nitrate. Since then, we
      have carried out a series of experiments to demonstrate that NO diffuses into the
      adjacent epithelium at cytotoxic levels. This diffusion results in disruption of
      the epithelial barrier function, exacerbation of inflammation, acceleration of
      columnar transformation in the esophagus (Barrett's esophagus) via the induction
      of caudal-type homeobox 2, and the shifting of carcinogenic N-nitroso compound
      formation from the luminal to epithelial compartment. These results suggest that,
      in addition to conventionally recognized causative factors, luminal NO could also
      be involved in the pathogenesis of the GERD spectrum. In addition, we recently
      showed that there is a prominent gender-related difference in NO-related
      cytotoxicity in the esophagus and that estrogen attenuated the esophageal tissue
      damage via the estrogen receptor in female rats. The role of estrogen in
      attenuating the esophageal tissue damage in NO-related esophageal damage could
      explain the well-recognized male predominance in the GERD spectrum in humans. 

PMID- 24863185
TI  - Management of chronic hepatitis B in children: an unresolved issue.
AB  - Although a rather benign course of chronic hepatitis B virus (HBV) infection
      during childhood has been described, 3-5% and 0.01-0.03% of chronic carriers
      develop cirrhosis or hepatocellular carcinoma before adulthood. Considering the
      whole lifetime, the risk of hepatocellular carcinoma rises to 9-24% and the
      incidence of cirrhosis to 2-3% per year. The aim of this article is to review the
      current knowledge regarding the natural history and treatment of chronic
      hepatitis B in children and to focus on critical aspects and unresolved questions
      in the management of childhood HBV infection. A literature search was carried out
      on MEDLINE, EMBASE, and Web of Science for articles published in English in peer
      reviewed journals from January 1980 to February 2013. The search terms used
      included "Hepatitis B virus infection," "children," "HBV," "interferon,"
      "lamivudine," "adefovir," "entecavir," and "tenofovir." Articles resulting from
      these searches and relevant references cited in the articles retrieved were
      reviewed. The current goals of therapy are to suppress viral replication, reduce
      liver inflammation, and reverse liver fibrosis. Therapeutic options for children
      are currently limited, and the risk for viral resistance to current and future
      therapies is a particular concern. Based on the data available at this time, it
      is the consensus of the panel that it is not appropriate to treat children in the
      immune-tolerant phase or in the inactive carrier state. For children in the
      immune-active or reactivation phases, liver histology can help guide treatment
      decisions. Outside of clinical trials, interferon is the agent of choice in most
      cases; currently, available nucleoside analogs are secondary therapies. 

PMID- 24863186
TI  - Long-term survival after surgical resection for huge hepatocellular carcinoma:
      comparison with transarterial chemoembolization after propensity score matching.
AB  - BACKGROUND AND AIMS: Surgical resection (SR) and transarterial chemoembolization
      (TACE) have been commonly applied for patients with huge hepatocellular carcinoma
      (HCC). However, optimal treatment has not been established. METHODS: Between 2000
      and 2009, 267 patients with huge HCC (>= 10 cm) underwent TACE and 84 underwent
      SR as the first treatment. Propensity score matching generated a matched cohort
      composed of 152 patients. We investigated overall survival and possible
      prognostic factors. RESULTS: At baseline, the surgery group showed a tendency to
      have solitary tumor (72.6% vs 39.3%, P < 0.001), less vessel invasion (29.8% vs
      51.3%, P < 0.001), and unilobar tumor extent (77.4% vs 50.9%, P < 0.001) than
      TACE group. During median follow up of 10 months (range: 0-103), the surgery
      group showed higher 1-, 3-, and 5-year overall survival rates than TACE group
      (73.8%, 54.8%, and 39.8% vs 37.8%, 16.3%, and 9.7%, respectively, P < 0.001). In
      the propensity score-matched cohort, baseline characteristics did not differ
      between the two groups. Surgery group showed higher 1-, 2-, and 3-year overall
      survival rates than TACE group (69.7%, 58.6%, and 51.7% vs 40.2%, 33.9%, and
      18.5%, respectively, P < 0.001) during median follow up of 14.5 months (range: 0
      103). Multivariate analysis revealed that male (HR 1.90; 95% CI, 1.01-3.58; P =
      0.048), albumin (HR 0.54; 95% CI, 0.34-0.85; P = 0.008), ascites (HR 1.77; 95%
      CI, 1.02-3.08; P = 0.044), and SR (HR 0.44; 95% CI, 0.28-0.70; P = 0.001) were
      the independent prognostic factors associated with survival. CONCLUSION:
      Comparing survival after SR and TACE, we showed that SR would be associated with
      better outcomes than TACE as the first treatment of huge HCC.

PMID- 24863187
TI  - The development of septation in the four-chambered heart.
AB  - The past decades have seen immense progress in the understanding of cardiac
      development. Appreciation of precise details of cardiac anatomy, however, has yet
      to be fully translated into the more general understanding of the changing
      structure of the developing heart, particularly with regard to formation of the
      septal structures. In this review, using images obtained with episcopic
      microscopy together with scanning electron microscopy, we show that the newly
      acquired information concerning the anatomic changes occurring during separation
      of the cardiac chambers in the mouse is able to provide a basis for understanding
      the morphogenesis of septal defects in the human heart. It is now established
      that as part of the changes seen when the heart tube changes from a short linear
      structure to the looped arrangement presaging formation of the ventricles, new
      material is added at both its venous and arterial poles. The details of these
      early changes, however, are beyond the scope of our current review. It is during
      E10.5 in the mouse that the first anatomic features of septation are seen, with
      formation of the primary atrial septum. This muscular structure grows toward the
      cushions formed within the atrioventricular canal, carrying on its leading edge a
      mesenchymal cap. Its cranial attachment breaks down to form the secondary foramen
      by the time the mesenchymal cap has used with the atrioventricular endocardial
      cushions, the latter fusion obliterating the primary foramen. Then the cap, along
      with a mesenchymal protrusion that grows from the mediastinal mesenchyme,
      muscularizes to form the base of the definitive atrial septum, the primary septum
      itself forming the floor of the oval foramen. The cranial margin of the foramen
      is a fold between the attachments of the pulmonary veins to the left atrium and
      the roof of the right atrium. The apical muscular ventricular septum develops
      concomitant with the ballooning of the apical components from the inlet and
      outlet of the ventricular loop. Its apical part is initially trabeculated. The
      membranous part of the septum is derived from the rightward margins of the
      atrioventricular cushions, with the muscularizing proximal outflow cushions
      fusing with the muscular septum and becoming the subpulmonary infundibulum as the
      aorta is committed to the left ventricle. Perturbations of these processes
      explain well the phenotypic variants of deficient atrial and ventricular
      septation.

PMID- 24863188
TI  - A clinical decision algorithm for hospital inpatients with impaired decision
      making capacity.
AB  - BACKGROUND: Impaired decision-making capacity is a frequent complication of
      inpatient hospitalization, with potential negative impacts on patients and the
      healthcare system. Studies of clinician behavior show difficulty in diagnosis and
      management of capacity impairment. Appropriate management of incapacitated
      patients may benefit safety, medical outcomes, and healthcare expenditure.
      OBJECTIVE: To create a clinical decision algorithm for identification and
      management of hospital inpatients with impaired capacity. METHODS: The Department
      of Risk Management at San Francisco General Hospital (SFGH) convened a
      multidisciplinary workgroup to improve management of incapacitated patients. The
      workgroup studied institutional data and case experience, solicited mental health
      expertise, and performed a brief review of published tools for management of
      incapacitated patients. The workgroup produced a clinical decision algorithm for
      hospital inpatients with impaired decision-making capacity. RESULTS: The
      algorithm is explained via 3 common scenarios, and notable details include
      identification and management in a single visual diagram, emphasis on safety
      planning for a high-risk subset of incapacitated patients, and explanation for
      multiple disciplines of consultation. The algorithm was disseminated to
      providers, workshops were conducted, and associated quality improvements were
      implemented. Initial feedback was positive, relating to clinical competency,
      decreased practice anxiety, and improved teamwork. CONCLUSIONS: Impaired decision
      making capacity is frequent among hospitalized patients, including at SFGH. An
      algorithm, based on institutional review and prior published work, is presented
      as an example to address the common challenge of acutely ill patients with
      impaired decision-making capacity.

PMID- 24863190
TI  - Supramolecular cyclodextrin pseudorotaxane hydrogels: a candidate for sustained
      release?
AB  - In this work, PEO-alpha-CD pseudorotaxane hydrogels were prepared. The gels were
      loaded with proteins, BSA and lysozyme, representing proteins with different
      molecular weights. The kinetics of protein release was studied. Factors such as
      PEO concentration, protein concentration and exposed surface area of the gels
      were investigated to understand their effects on the release of the encapsulated
      cargo. Erosion of the gel surface appeared to be the dominant factor for release
      of the proteins. Fitting the data to various models supported our hypothesis that
      the mechanism of release was primarily erosion-driven as the data was best
      described by zero order, power law and Hopfenberg model. The linear relationship
      between the amount of mass loss and time establishes the erosion of the polymer
      gel matrix to be the key factor for drug release. 

PMID- 24863189
TI  - Iminodiacetic acid functionalized porous hydroxyapatite nanoparticles for
      capturing histidine-tagged proteins.
AB  - A simple strategy has been developed to synthesize hydroxyapatite (HAP)
      nanoparticles (NPs) in a simulated body fluid (SBF). The HAP NPs have an average
      diameter of 50nm and present porous structure. By taking advantage of surface
      hydroxyl groups, the HAP NPs are further modified with iminodiacetic acid (IDA),
      followed by chelating Ni(2+) ions. The HAP/IDA-Ni(2+) NPs as novel adsorbent can
      capture directly histidine-tagged (His-tagged) proteins from the mixture of lysed
      cells without sample pretreatment. Results indicated that the HAP/IDA-Ni(2+) NPs
      present negligible nonspecific adsorption and high protein binding ability, and
      their specificity and affinity toward His-tagged proteins can remain after 5
      times of recycling. The HAP/IDA-Ni(2+) NPs are especially suitable for
      purification of His-tagged proteins with low molecule weight. 

PMID- 24863191
TI  - Mesoporous carbon with spherical pores as a carrier for celecoxib with needle
      like crystallinity: improve dissolution rate and bioavailability.
AB  - The purposes of this investigation are to design mesoporous carbon (MC) with
      spherical pore channels and incorporate CEL to it for changing its needlelike
      crystal form and improving its dissolution and bioavailability. A series of solid
      state characterization methods, such as SEM, TEM, DSC and XRD, were employed to
      systematically investigate the existing status of celecoxib (CEL) within the pore
      channels of MC. The pore size, pore volume and surface area of samples were
      characterized by nitrogen physical absorption. Gastric mucosa irritation test was
      carried out to evaluate the safety of mesoporous carbon as a drug carrier.
      Dissolution tests and in vivo pharmacokinetic studies were conducted to confirm
      the improvement in drug dissolution kinetics and oral bioavailability. Uptake
      experiments were conducted to investigate the mechanism of the improved oral
      bioavailability. The results of solid state characterization showed that MC was
      prepared successfully and CEL was incorporated into the mesoporous channels of
      the MC. The crystallinity of CEL in MC was affected by different loading methods,
      which involve evaporation method and melting method. The dissolution rate of CEL
      from MC was found to be significantly higher than that of pure CEL, which
      attributed to reduced crystallinity of CEL. The gastric mucosa irritation test
      indicated that the MC caused no harm to the stomach and produced a protective
      effect on the gastric mucosa. Uptake experiments indicated that MC enhanced the
      amount of CEL absorbed by Caco-2 cells. Moreover, oral bioavailability of CEL
      loaded within the MC was approximately 1.59-fold greater than that of commercial
      CEL. In conclusion, MC was a safe carrier to load water insoluble drug by
      controlling the crystallinity or crystal form with improvement in drug
      dissolution kinetics and oral bioavailability. 

PMID- 24863192
TI  - Hierarchical porous bioactive glasses/PLGA-magnetic SBA-15 for dual-drug release.
AB  - The hierarchical porous bioglass combined with magnetic SBA-15 was synthesized.
      The bioactive glass materials possess a hierarchical porous structure with the
      macroporous (50MUm) and the mesoporous (3.86nm) structures derived from the plant
      template (cattail stem) and triblock polyethylene oxide-propylene oxide block
      copolymer (P123), respectively. Magnetic SBA-15 was synthesized by adopting the
      post assembly method using Fe(NO3)3 as iron source and ethylene glycol as
      reduction. After coating PLGA, PLGA-IBU-magnetic SBA-15 also possessed super
      paramagnetism and the corresponding saturation magnetizations (Ms) could reach
      2.6emug(-1). Metformin HCl (MH) and ibuprofen (IBU) were used as model drugs, and
      the drug release kinetics was studied. MH and IBU could release 60% and 85% from
      the sample respectively. The system shows excellent dual-drug controlled delivery
      performance and good bioactivity in vitro that leads to good potential
      application on bone regeneration. 

PMID- 24863193
TI  - Production and characterization of natural rubber-Ca/P blends for biomedical
      purposes.
AB  - This study presents the development of natural rubber-Ca/P blends, as promising
      candidates for biomedical purposes. The specific objective was the incorporation
      of Ca/P into a natural rubber polymeric matrix. Ca/P crystalline phases were
      synthesized by the sol-gel method and the polymeric matrices were produced using
      natural rubber extracted from latex of the Hevea brasiliensis. The shape and size
      of natural rubber particles present in the NR membrane, as well as, the way the
      Ca/P powder grains aggregate in the polymeric matrix were investigated, giving
      information about the interactions between the Ca/P and the natural rubber
      particles. Confocal fluorescence scanning microscopy measurements allowed us to
      propose a structure where the Ca/P grains are surrounded by natural rubber
      particles. This structure may mediate Ca(2+) release for tissue regeneration. The
      system investigated may open new horizons for development of a bandage which
      provides the controlled-release of biomaterials. 

PMID- 24863194
TI  - Physical and structural characterisation of starch/polyester blends with tartaric
      acid.
AB  - Starch/PBAT blends were produced by reactive extrusion with tartaric acid (TA) as
      an additive. The effects of TA, glycerol and starch+PBAT on the mechanical,
      optical and structural properties of the films were evaluated, with formulations
      based in a constrained mixture design. Tartaric acid acts as a compatibiliser and
      promotes the acid hydrolysis of starch chains. These two functions explain the
      observed film resistance and opacity. TA reduced the weight loss in water.
      Scanning electron microscopy (SEM) images showed that TA reduces the interfacial
      tension between the polymeric phases, resulting in more homogeneous films.
      Nuclear magnetic resonance ((13)C CPMAS) and Fourier transform infrared
      spectroscopy (FT-IR) suggest that tartaric acid is able to react with the
      hydroxyl groups of the starch by esterification/transesterification reactions,
      confirming its role as a compatibiliser. The addition of TA results in materials
      with better properties that are suitable for use in food packaging. 

PMID- 24863195
TI  - Biphasic products of dicalcium phosphate-rich cement with injectability and
      nondispersibility.
AB  - In this study, a calcium phosphate cement was developed using tetracalcium
      phosphate and surface-modified dicalcium phosphate anhydrous (DCPA). This
      developed injectable bone graft substitute can be molded to the shape of the bone
      cavity and set in situ through the piping system that has an adequate mechanical
      strength, non-dispersibility, and biocompatibility. The materials were based on
      the modified DCPA compositions of calcium phosphate cement (CPC), where the phase
      ratio of the surface-modified DCPA is higher than that of the conventional CPC
      for forming dicalcium phosphate (DCP)-rich cement. The composition and morphology
      of several calcium phosphate cement specimens during setting were analyzed via X
      ray diffractometry and transmission electron microscopy coupled with an energy
      dispersive spectroscopy system. The compressive strength of DCP-rich CPCs was
      greater than 30MPa after 24h of immersion in vitro. The reaction of the CPCs
      produced steady final biphasic products of DCPs with apatite. The composites of
      calcium phosphate cements derived from tetracalcium phosphate mixed with surface
      modified DCPA exhibited excellent mechanical properties, injectability, and
      interlocking forces between particles, and they also featured nondispersive
      behavior when immersed in a physiological solution. 

PMID- 24863197
TI  - In vitro controlled release of vitamin C from Ca/Al layered double hydroxide drug
      delivery system.
AB  - A new drug delivery system for vitamin C (VC), Ca/Al layered double hydroxide
      (LDH), is demonstrated in this work. VC anions were intercalated successfully in
      the Ca/Al LDH gallery by a coprecipitation method. The interlayer space of 9.8A
      suggests that VC anions are vertical to the LDH layers in the form of
      interdigitated bilayer. The loading of VC in LDH is 36.4wt.%. The thermal
      stability of VC is significantly enhanced after intercalation. In vitro VC
      release results show that the release time of VC in a phosphate buffer at pH7.4
      was significantly extended, and the maximal percentage of VC released is 80% of
      the total. The Avrami-Erofe'ev equation most satisfactorily explains the release
      kinetics of VC, which is that the release of VC is mainly dominated by the ion
      exchange reaction. 

PMID- 24863196
TI  - Doxorubicin loaded folate-targeted carbon nanotubes: preparation, cellular
      internalization, in vitro cytotoxicity and disposition kinetic study in the
      isolated perfused rat liver.
AB  - The objective of this study was to use the functionalized multi-wall carbon
      nanotubes (CNTs) for the delivery of doxorubicin (DOX). Polyethylene glycol (PEG)
      chains are attached to CNTs then folate-conjugation of PEGylated CNTs was
      prepared. The amount of drug loading was calculated by the Multivariate
      Calibration Method for simultaneous quantification of DOX and CNTs. Cytotoxicity
      was evaluated using the folate receptor-positive HeLa cell line. To assess
      distribution and elimination of free DOX and drug-loaded CNTs, a recirculating
      rat liver perfusion system was used and pharmacokinetic parameters were
      calculated using non-compartmental analysis. Loading efficiency of 84.3+/-3.1%
      and 49.3+/-5.4% was calculated for low-PEGylated and high-PEGylated CNTs
      respectively. A higher release rate of DOX was achieved at a higher amount of
      PEGylation. Folate-targeted CNTs expressed a 3.2-fold decrease in IC50 value
      compared with non-targeted CNTs. The result from liver perfusion experiments
      revealed that DOX accumulation in the liver was higher when PEGylation was lower.
      There was a 2.4-fold decrease in the elimination rate constant compared to free
      DOX, which was attributed to the redistribution of DOX from hepatocytes in a
      sustained release pattern that is consistent with an increase in the mean
      residence time and prolonged circulation. In conclusion, folate-targeted CNTs
      show great potential as a targeted anticancer delivery system. 

PMID- 24863198
TI  - Novel selenium containing boro-phosphate glasses: preparation and structural
      study.
AB  - We synthesized a new boro-phosphate glass system with different %mol SeO2 content
      by conventional melt quenching technique. All samples were obtained in a glassy
      state with the vitreous structure confirmed by X-ray diffraction analysis.
      Scanning electron microscopy (SEM) revealed some non-homogeneous domains on the
      glasses surface, and their tendency to link each other once the selenium oxide
      content increases. Energy-dispersive X-ray analysis (EDAX) indicated similar
      elemental composition in different regions of each sample. X-ray photoelectron
      spectroscopy (XPS) was used to determine the nature of chemical bonding and the
      elemental composition at the sample surfaces, and Fourier transform infrared (FT
      IR) spectroscopy was used to determine the structural groups in the obtained
      glass structure. Based on FT-IR results, the glass structure at short range order
      consists mainly of small phosphate units such as pyrophosphate (i.e. P2O7(4-)
      dimmers or terminating groups at the end of phosphate chains) and some
      metaphosphate (i.e. PO3(-) middle groups in the phosphate chains) units. The
      boron atoms are mainly placed in three-coordinated sites in BO3 or BO2O(-) units.
      A small contribution of BO4(-) units was also detected from the FT-IR spectra of
      glasses. For SeO2 content higher than 5mol%, the modifier role of selenium ions
      is strongly reflected on the local structure dominated in this case by
      pyrophosphate units. 

PMID- 24863199
TI  - Electrophoretic deposition of zinc-substituted hydroxyapatite coatings.
AB  - Zinc-substituted hydroxyapatite nanoparticles synthesized by the co-precipitation
      method were used to coat stainless steel plates by electrophoretic deposition in
      n-butanol with triethanolamine as a dispersant. The effect of zinc concentration
      in the synthesis on the morphology and microstructure of coatings was
      investigated. It is found that the deposition current densities significantly
      increase with the increasing zinc concentration. The zinc-substituted
      hydroxyapatite coatings were analyzed by X-ray diffraction, scanning electron
      microscopy and Fourier transform infrared spectroscopy. It is inferred that
      hydroxyapatite and triethanolamine predominate in the chemical composition of
      coatings. With the increasing Zn/Ca ratios, the contents of triethanolamine
      decrease in the final products. The triethanolamine can be burnt out by heat
      treatment. The tests of adhesive strength have confirmed good adhesion between
      the coatings and substrates. The formation of new apatite layer on the coatings
      has been observed after 7days of immersion in a simulated body fluid. In summary,
      the results show that dense, uniform zinc-substituted hydroxyapatite coatings are
      obtained by electrophoretic deposition when the Zn/Ca ratio reaches 5%. 

PMID- 24863200
TI  - An "off-on" fluorescent and colorimetric probe bearing fluorescein moiety for
      Mg(2+) and Ca(2+) via a controlled supramolecular approach.
AB  - In the present work, a new kind of fluorescein-based chemosensor L was designed
      and synthesized to selectively recognize Ca(2+) or Mg(2+) over other competing
      ions. The chemosensor showed "off-on" fluorescent and color changes upon the
      addition of Ca(2+) and Mg(2+). The dynamic binding events with the formation of
      1:1(L/M) and 1:2(L/M) complexes were examined. The cation-driven conformation
      changes of L were understood and proposed rationally by the UV-vis, FL, and
      (1)HNMR titrations. By this allosteric effect, Ca(2+) and Mg(2+) could be
      selectively recognized with the 1:2 stoichiometry by fluorescent changes, which
      were different from other known reports on chemosensors that the host-cation
      complexion was exploited for controlling chromophore interaction as the model of
      signaling. 

PMID- 24863201
TI  - Voltammetric behavior of dopamine at a glassy carbon electrode modified with
      NiFe(2)O(4) magnetic nanoparticles decorated with multiwall carbon nanotubes.
AB  - Voltammetric behavior of dopamine was studied on a glassy carbon electrode (GCE)
      modified-NiFe(2)O(4) magnetic nanoparticles decorated with multiwall carbon
      nanotubes. Impedance spectroscopy and cyclic voltammetry were used to
      characterize the behavior of dopamine at the surface of modified-GCE. The
      modified electrode showed a synergic effect toward the oxidation of dopamine. The
      oxidation peak current is increased linearly with the dopamine concentration (at
      pH7.0) in wide dynamic ranges of 0.05-6.0 and 6.0-100MUmolL(-1) with a detection
      limit of 0.02MUmolL(-1), using differential pulse voltammetry. The selectivity of
      the method was studied and the results showed that the modified electrode is free
      from interference of organic compounds especially ascorbic acid, uric acid,
      cysteine and urea. Its applicability in the determination of dopamine in
      pharmaceutical, urine samples and human blood serum was also evaluated. The
      proposed electrochemical sensor has appropriate properties such as high
      selectivity, low detection limit and wide linear dynamic range when compared with
      that of the previous reported papers for dopamine detection.

PMID- 24863202
TI  - Application of N-doped graphene modified carbon ionic liquid electrode for direct
      electrochemistry of hemoglobin.
AB  - Nitrogen-doped graphene (NG) was synthesized and used for the investigation on
      direct electrochemistry of hemoglobin (Hb) with a carbon ionic liquid electrode
      as the substrate electrode. Due to specific characteristics of NG such as
      excellent electrocatalytic property and large surface area, direct electron
      transfer of Hb was realized with enhanced electrochemical responses appearing.
      Electrochemical behaviors of Hb on the NG modified electrode were carefully
      investigated with the electrochemical parameters calculated. The Hb modified
      electrode exhibited excellent electrocatalytic reduction activity toward
      different substrates, such as trichloroacetic acid and H2O2, with wider dynamic
      range and lower detection limit. These findings show that NG can be used for the
      preparation of chemically modified electrodes with improved performance and has
      potential applications in electrochemical sensing. 

PMID- 24863203
TI  - A low detection limit penicillin biosensor based on single graphene nanosheets
      preadsorbed with hematein/ionic liquids/penicillinase.
AB  - In this study, we reported on a low detection limit penicillin biosensor with
      layer-by-layer (LbL) film containing single-graphene nanosheets (SGNs)
      preadsorbed with hematein, ionic liquids (ILs) and penicillinase. The
      penicillinase catalyzes the hydrolysis of penicillin to penicilloic acid, where
      H(+) is liberated and monitored amperometrically with hematein as a pH indicator.
      The SGN-hematein/ILs/penicillinase biosensor exhibited excellent performance for
      penicillin in PBS with a wide range from 1.25*10(-13) to 7.5*10(-3)M, and a low
      detection limit of 10(-13)M (0.04ppt, S/N>=3). Furthermore, the detection of
      penicillin concentration in real sample (milk) had acceptable accuracy with the
      assay system. 

PMID- 24863204
TI  - Strain rate effects on the mechanical properties and fracture mode of skeletal
      muscle.
AB  - The present study aimed to characterize the mechanical response of beagle
      sartorius muscle fibers under strain rates that increase logarithmically
      (0.1mm/min, 1mm/min and 10mm/min), and provide an analysis of the fracture
      patterns of these tissues via scanning electron microscopy (SEM). Muscle tissue
      from dogs' sartorius was excised and test specimens were sectioned with a lancet
      into sections with nominal length, width, and thickness of 7, 2.5 and 0.6mm,
      respectively. Trimming of the tissue was done so that the loading would be
      parallel to the direction of the muscle fiber. Samples were immediately tested
      following excision and failures were observed under the SEM. No statistically
      significant difference was observed in strength between the 0.1mm/min (2.560+/
      0.37MPa) and the 1mm/min (2.702+/-0.55MPa) groups. However, the 10mm/min group
      (1.545+/-0.50MPa) had a statistically significant lower strength than both the
      1mm/min group and the 0.1mm/min group with p<0.01 in both cases. At the 0.1mm/min
      rate the primary fracture mechanism was that of a shear mode failure of the
      endomysium with a significant relative motion between fibers. At 1mm/min this
      continues to be the predominant failure mode. At the 10mm/min strain rate there
      is a significant change in the fracture pattern relative to other strain rates,
      where little to no evidence of endomysial shear failure nor of significant motion
      between fibers was detected. 

PMID- 24863205
TI  - Amperometric sensing of anti-HIV drug zidovudine on Ag nanofilm-multiwalled
      carbon nanotubes modified glassy carbon electrode.
AB  - The zidovudine (ZDV) is the first drug approved for the treatment of HIV virus
      infection. The detection and determination of this drug are very importance in
      human serum because of its undesirable effects. A new ZDV sensor was fabricated
      on the basis of nanocomposite of silver nanofilm (Ag-NF) and multiwalled carbon
      nanotubes (MWCNTs) immobilized on glassy carbon electrode (GCE). The modified
      electrodes were characterized by scanning electron microscopy (SEM), energy
      dispersive X-ray spectroscopy (EDS), X-ray diffraction (XRD), cyclic voltammetry
      (CV), and linear sweep voltammetry (LSV) techniques. Results showed that the
      electrodeposited silver has a nanofilm structure and further electrochemical
      studies showed that the prepared nanocomposite has high electrocatalytic activity
      and is appropriate for using in sensors. The amperometric technique under optimal
      conditions is used for the determination of ZDV ranging from 0.1 to 400ppm
      (0.37MUM-1.5mM) with a low detection limit of 0.04ppm (0.15MUM) (S/N=3) and good
      sensitivity. The prepared sensor possessed accurate and rapid response to ZDV and
      shows an average recovery of 98.6% in real samples. 

PMID- 24863206
TI  - Formulation of porous poly(lactic-co-glycolic acid) microparticles by
      electrospray deposition method for controlled drug release.
AB  - In the present study, the electrospray deposition was successfully applied to
      prepare the porous poly(lactic-co-glycolic acid) (PLGA) microparticles by one
      step processing. Metronidazole was selected as the model drug. The porous PLGA
      microparticles had high drug loading and low density, and the porous structure
      can be observed by scanning electron microscope (SEM) and transmission electron
      microscopy (TEM). The production time has been shortened considerably compared
      with that of the traditional multi-emulsion method. In addition, no chemical
      reaction occurred between the drug and polymer in the preparation of porous
      microparticles, and the crystal structure of drug did not change after entrapment
      into the porous microparticles. The porous microparticles showed a sustained
      release in the simulated gastric fluid, and the release followed non-Fickian or
      case II transport. Furthermore, porous microparticles showed a slight
      cytotoxicity in vitro. The results indicated that electrospray deposition is a
      good technique for preparation of porous microparticles, and the low-density
      porous PLGA microparticles has a potential for the development of gastroretentive
      systems or for pulmonary drug delivery. 

PMID- 24863207
TI  - Fabrication and characterization of novel biomimetic
      PLLA/cellulose/hydroxyapatite nanocomposite for bone repair applications.
AB  - The purpose of this research is to develop and characterize a novel biomimetic
      nanocomposite that closely mimics the properties of real bone such as morphology,
      composition and mechanical characteristics. This novel porous nanocomposite is
      composed of cotton-sourced cellulose microcrystals, hydroxyapatite nanoparticles
      and poly l-lactide acid. A unique combination of commonly used fabrication
      procedures has been developed including pre-treatment of particles using a
      coupling agent. The effect of various weight ratios of the reinforcing agents was
      evaluated to assess their influence on the chemical, thermal, and mechanical
      properties of the nanocomposites. The prepared nanocomposites were characterized
      using Fourier transform infrared spectroscopy, scanning electron microscopy,
      differential scanning calorimetry and compression testing. Our results indicated
      the presence of molecular interactions between all components leading to an
      increase of the crystallinity of the polymer from 50% to 80%. Compression test
      results revealed that increasing the weight ratio of microcrystalline
      cellulose/poly l-lactide acid and hydroxyapatite/poly l-lactide acid from 0.1 to
      0.5 enhanced the compressive yield stress from 0.127 to 2.2MPa and The Young's
      modulus from 6.6 to 38MPa, respectively. It was found that the fabricated
      nanocomposites are comparable with the trabecular bone from compositional,
      structural, and mechanical point of view. 

PMID- 24863209
TI  - Nanocrystalline hydroxyapatite doped with selenium oxyanions: a new material for
      potential biomedical applications.
AB  - Selenium-substituted hydroxyapatites containing selenate SeO4(2-) or selenite
      SeO3(2-) ions were synthesized using a wet precipitation method. The selenium
      content was determined by atomic absorbance spectrometry. The raw, unsintered
      powders were also characterized using powder X-ray diffraction, middle-range FT
      IR spectroscopy and transmission electron microscopy with energy-dispersive X-ray
      spectroscopic microanalysis. The synthesized apatites were found to be pure and
      nanocrystalline with a crystal size similar to that in bone mineral. The
      incorporation of selenium oxyanions into the crystal lattice was confirmed. The
      toxicity of hydroxyapatites containing selenite or selenate ions was evaluated
      with a protozoan assay and bacterial luminescence test. 

PMID- 24863208
TI  - Effect of multiwall carbon nanotube reinforcement on coaxially extruded cellular
      vascular conduits.
AB  - Due to its abundant source, good biocompatibility, low price and mild
      crosslinking process, alginate is an ideal selection for tissue engineering
      applications. In this work, alginate vascular conduits were fabricated through a
      coaxial extrusion-based system. However, due to the inherent weak mechanical
      properties of alginate, the vascular conduits are not capable of biomimicking
      natural vascular system. In this paper, multiwall carbon nanotubes (MWCNT) were
      used to reinforce vascular conduits. Mechanical, dehydration, swelling and
      degradation tests were performed to understand influences of MWCNT reinforcement.
      The unique mechanical properties together with perfusion and diffusional
      capability are two important factors to mimic the nature. Thus, perfusion
      experiments were also conducted to explore the MWCNT reinforcement effect. In
      addition, cell viability and tissue histology were conducted to evaluate the
      biological performance of conduits both in short and long term for MWCNT
      reinforcement. 

PMID- 24863210
TI  - Aligned porous barium titanate/hydroxyapatite composites with high piezoelectric
      coefficients for bone tissue engineering.
AB  - It was proposed that the piezoelectric effect played an important physiological
      role in bone growth, remodelling and fracture healing. An aligned porous
      piezoelectric composite scaffold was fabricated by freeze casting
      hydroxyapatite/barium titanate (HA/BT) suspensions. The highest compressive
      strength and lowest porosity of 14.5MPa and 57.4% with the best parallelism of
      the pore channels were achieved in the HA10/BT90 composite. HA30/BT70 and
      HA10/BT90 composites exhibited piezoelectric coefficient d33 of 1.2 and 2.8pC/N,
      respectively, both of which were higher than the piezoelectric coefficient of
      natural bone. Increase of the solid loading of the suspension and solidification
      velocity led to the improvement of piezoelectric coefficient d33. Meanwhile,
      double-templates resulted in the coexistence of lamellar pores and aligned macro
      pores, exhibiting the ability to produce an oriented long-range ordered
      architecture. The manipulation flexibility of this method indicated the potential
      for customized needs in the application of bone substitute. An MTT assay
      indicated that the obtained scaffolds had no cytotoxic effects on L929 cells. 

PMID- 24863211
TI  - Bioactive, mechanically favorable, and biodegradable copolymer nanocomposites for
      orthopedic applications.
AB  - We report the synthesis of mechanically favorable, bioactive, and biodegradable
      copolymer nanocomposites for potential bone applications. The nanocomposites
      consist of in situ polymerized biodegradable copolyester with hydroxyapatite
      (HA). Biodegradable copolyesters comprise carboxy terminated poly(propylene
      fumarate) (CT-PPF) and poly(trimethylol propane fumarate co mannitol sebacate)
      (TF-Co-MS). Raman spectral imaging clearly reveals a uniform homogenous
      distribution of HA in the copolymer matrix. The mechanical studies reveal that
      improved mechanical properties formed when crosslinked with methyl methacrylate
      (MMA) when compared to N-vinyl pyrrolidone (NVP). The SEM micrographs of the
      copolymer nanocomposites reveal a serrated structure reflecting higher mechanical
      strength, good dispersion, and good interfacial bonding of HA in the polymer
      matrix. In vitro degradation of the copolymer crosslinked with MMA is relatively
      more than that of NVP and the degradation decreases with an increase in the
      amount of the HA filler. The mechanically favorable and degradable MMA based
      nanocomposites also have favorable bioactivity, blood compatibility,
      cytocompatibility and cell adhesion. The present nanocomposite is a more
      promising material for orthopedic applications. 

PMID- 24863212
TI  - Development and evaluation of pH-sensitive sodium alginate/chitosan
      microparticles containing the antituberculosis drug rifampicin.
AB  - This paper describes the encapsulation of a high molecular weight molecule
      rifampicin (RIF) in sodium alginate/chitosan microparticles, which provided
      controlled-release when evaluated in vitro. The microparticles were prepared by
      the coacervation technique. To evaluate and select the best encapsulation method
      two approaches were applied: coacervation (MCP method 1) and impregnation (MCP
      method 2). The microparticles obtained were analyzed by DSC, DRIFT, XRD and SEM
      and also the loading efficiency, swelling degree (SD) and in vitro release were
      determined. The results obtained showed that the alginate/chitosan microparticles
      represent an efficient system for the controlled-release of RIF. At acidic pH,
      the release of 20% of the drug occurred in 2h, and at pH6.8 a rapid increase in
      the release rate was observed up to 100%. The mechanism involved in the release
      was Super Case II kinetics since n>1 (n=1.09 and 1.13 for microparticles produced
      by methods 1 and 2, respectively), indicating that the release was related to
      diffusion, swelling, relaxation and erosion processes. The dissolution
      efficiencies were similar for both formulations, and the f2 values of >=50
      indicated the similarity between the two profiles, under the assumption of a
      maximum allowable difference of 10%. 

PMID- 24863213
TI  - Generation of poly(N-vinylpyrrolidone) nanofibres using pressurised gyration.
AB  - The ability to generate nanofibres useful for biomedical applications at bench
      and at a larger scale is a significant manufacturing challenge. In this study, we
      demonstrate that it is possible to generate nanofibre meshes of poly(N
      vinylpyrrolidone) (PVP) using pressurised gyration. The effects of altering
      polymer molecular weight and concentration on fibre morphology and size have been
      investigated, with identification of minimum values for both parameters for
      successful fibre fabrication. In addition, we note that changing the molecular
      weight may result in changes to the Fourier Transform Infrared (FTIR) spectra
      associated with changes in fibre intramolecular bond strength and arrangement.
      Overall the study has demonstrated that pressure gyration represents a feasible
      means of producing nanofibres (470-970nm) on a scale commensurate with commercial
      viability and have identified key parameters that influence mesh structure. 

PMID- 24863214
TI  - Eco-designed biohybrids based on liposomes, mint-nanosilver and carbon nanotubes
      for antioxidant and antimicrobial coating.
AB  - Noncovalent entities (consisting of liposomes, phyto-nanosilver and carbon
      nanotubes) with interesting properties were constructed by a "green" bottom-up
      method. Phytosynthesis of silver nanoparticles using the Mentha piperita extract
      combines the benefits of this herb with the interesting properties of silver. The
      obtained silver-based biohybrids showed antioxidant and antimicrobial properties
      that have been considerable improved in the presence of carbon nanotubes. Thus
      the eco-designed bioconstructs consisting of cholesterol-containing liposomes,
      phytonanosilver and carbon nanotubes exhibited high antioxidant activity
      (AA=90.8%) and have been shown to be strong biocides offering inhibition zone of
      25mm against Escherichia coli and 23mm against Staphylococcus aureus and
      Enterococcus faecalis. 

PMID- 24863215
TI  - MC3T3-E1 cell response of amorphous phase/TiO2 nanocrystal composite coating
      prepared by microarc oxidation on titanium.
AB  - Bioactive amorphous phase/TiO2 nanocrystal (APTN) composite coatings were
      fabricated by microarc oxidation (MAO) on Ti. The APTN coatings are composed of
      much amorphous phase with Si, Na, Ca, Ti and O elements and a few TiO2
      nanocrystals. With increasing applied voltage, the micropore density of the APTN
      coating decreases and the micropore size of the APTN coating increases. The
      results indicate that less MC3T3-E1 cells attach on the APTN coatings as compared
      to Ti. However, the APTN coatings greatly enhance the cell proliferation ability
      and the activity of alkaline phosphatase. The amorphous phase and the
      concentrations of the released Ca and Si from the APTN coatings during cell
      culture have significant effects on the cell response. 

PMID- 24863216
TI  - Sulfonate groups grafted on Ti6Al4V favor MC3T3-E1 cell performance in serum free
      medium conditions.
AB  - Ten years ago, we synthesized "bioactive model polymers" bearing sulfonate groups
      and proposed a mechanism of their modulation effect at different steps of the
      cell response. Then, we set up the grafting of polymers bearing sulfonate on
      Ti6Al4V surfaces by a grafting "from" technique making sure of the creation of
      covalent bonds between the grafted polymer and the Ti6Al4V surface. We have
      checked and confirmed the positive effect of grafted sulfonate groups on the
      osteoblastic cell response in vivo and in vitro but we did not elucidate the
      mechanism. The aim of this basic work consists first in investigating the role of
      sulfonate groups in the presence and in the absence of proteins at early stages
      of the osteointegration process on poly(sodium styrene sulfonate) poly(NaSS)
      grafted and ungrafted Ti6Al4V surfaces, in vitro. To understand the role of
      poly(NaSS) grafted chains on osteoblast-like cell response and to
      confirm/elucidate the importance of fetal bovine serum (FBS) proteins in the
      culture medium, MC3T3-E1 cells were seeded onto poly(NaSS) grafted and non
      grafted Ti6Al4V surfaces. Cultures were carried out in a complete (10% FBS) and
      in a non-complete medium (without FBS). Cell viability assay, cell attachment
      number and cell adhesion strength were followed up to 3days of culture. The
      presence of proteins enhanced cell growth and development whatever the surface
      and the presence of sulfonate groups enhanced the cell attachment even in the
      absence of proteins, which suggests and confirms that the sulfonate groups can
      modify the activity of cells such as the secretion of binding proteins.
      Statistical differences were found in the attachment strength tests on poly(NaSS)
      grafted and ungrafted surfaces and showed that the sulfonate groups play an
      important role in the cell resistance to shear stress. 

PMID- 24863217
TI  - Biofabrication of Ag nanoparticles using Sterculia foetida L. seed extract and
      their toxic potential against mosquito vectors and HeLa cancer cells.
AB  - A one-step and eco-friendly process for the synthesis of silver-(protein-lipid)
      nanoparticles (Ag-PL NPs) (core-shell) has been developed using the seed extract
      from wild Indian Almond tree, Sterculia foetida (L.) (Sterculiaceae). The
      reaction temperature played a major role in controlling the size and shell
      formation of NPs. The amount of NPs synthesized and qualitative characterization
      was done by UV-vis spectroscopy and transmission electron microscopy (TEM),
      respectively. TEM studies exhibited controlled dispersity of spherical shaped NPs
      with an average size of 6.9+/-0.2nm. Selected area electron diffraction (SAED)
      and X-ray diffraction (XRD) revealed 'fcc' phase and crystallinity of the
      particles. X-ray photoelectron spectroscopy (XPS) was used to identify the
      protein-lipid (PL) bilayer that appears as a shell around the Ag core particles.
      The thermal stability of the Ag-PL NPs was examined using thermogravimetric
      analysis (TGA). Further analysis was carried out by using Fourier transform
      infrared spectroscopy (FTIR), where the spectra provided evidence for the
      presence of proteins and lipid moieties ((2n-octylcycloprop-1-enyl)-octanoic acid
      (I)), and their role in synthesis and stabilization of Ag NPs. This is the first
      report of plant seed assisted synthesis of PL conjugated Ag NPs. These formed Ag
      PL NPs showed potential mosquito larvicidal activity against Aedes aegypti (L.),
      Anopheles stephensi Liston and Culex quinquefasciatus Say. These Ag-PL NPs can
      also act as promising agents in cancer therapy. They exhibited anti-proliferative
      activity against HeLa cancer cell lines and a promising toxicity was observed in
      a dose dependent manner. Toxicity studies were further supported by the cellular
      DNA fragmentation in the Ag-PL NPs treated HeLa cells. 

PMID- 24863219
TI  - Temperature and saturation dependence in the vapor sensing of butterfly wing
      scales.
AB  - The sensing of gasses/vapors in the ambient air is the focus of attention due to
      the need to monitor our everyday environment. Photonic crystals are sensing
      materials of the future because of their strong light-manipulating properties.
      Natural photonic structures are well-suited materials for testing detection
      principles because they are significantly cheaper than artificial photonic
      structures and are available in larger sizes. Additionally, natural photonic
      structures may provide new ideas for developing novel artificial photonic
      nanoarchitectures with improved properties. In the present paper, we discuss the
      effects arising from the sensor temperature and the vapor concentration in air
      during measurements with a photonic crystal-type optical gas sensor. Our results
      shed light on the sources of discrepancy between simulated and experimental
      sensing behaviors of photonic crystal-type structures. Through capillary
      condensation, the vapors will condensate to a liquid state inside the
      nanocavities. Due to the temperature and radius of curvature dependence of
      capillary condensation, the measured signals are affected by the sensor
      temperature as well as by the presence of a nanocavity size distribution. The
      sensing materials used are natural photonic nanoarchitectures present in the wing
      scales of blue butterflies. 

PMID- 24863218
TI  - Facile synthesis of PSMA-g-3ABA/MWCNTs nanocomposite as a substrate for
      hemoglobin immobilization: application to catalysis of H(2)O(2).
AB  - The new nanocomposite films based on poly(styrene-alternative-maleic anhydride)
      grafted to 3-aminobenzoic acid (PSMA-g-3ABA) and multi-walled carbon nanotubes
      (MWCNTs) were applied to immobilize hemoglobin (Hb) for biosensor fabrication
      (PSMA-g-3ABA/MWCNTs). Electrochemical impedance spectroscopy was used to confirm
      the adsorption of Hb onto the surface of PSMA-g-3ABA/MWCNTs. The immobilized Hb
      maintains its bioactivities and displays an excellent electrochemical behavior.
      The biosensor was used to catalyze the reduction of hydrogen peroxide. The
      electrocatalytic response showed a linear dependence on the H2O2 concentration
      ranging widely from 1.0*10(-6)M to 5.0*10(-4)M with a detection limit of 3.2*10(
      7)M. The apparent Michaelis-Menten constant of Hb on the modified electrode was
      estimated to be 0.22mM. The proposed method opens a way to develop biosensors by
      using nanostructured materials with low electrical conductivity. 

PMID- 24863220
TI  - Investigation of the inhibitory effects of TiO(2) on the beta-amyloid peptide
      aggregation.
AB  - TiO2 thin films are of great interest as biocompatible coatings and also as
      photocatalytic self-cleaning and antimicrobial coatings. In this work we used
      beta-amyloid as a model for infectious protein to investigate the attachment and
      photocatalytic degradation. TiO2 films were prepared on stainless steel
      substrates using magnetron sputtering. The films were characterised before and
      after exposure to beta-amyloid (1-42), using XRD, Raman spectroscopy, XPS and
      AFM. The TiO2 film was mostly composed of the anatase phase with a relatively
      high surface roughness. The presence of Raman peaks at 1668cm(-1) and 1263cm(-1),
      with the XPS spectral feature for nitrogen at 400eV, confirmed the adsorption of
      amyloid on surface. Following exposure of the beta-amyloid contaminated TiO2 to
      UV-B irradiation a slight shift of amide modes was observed. Furthermore, the
      amide I spectra show an overall decrease in alpha-helix content with presence of
      a minor peak around 1591cm(-1), which is related to tryptophanyl and tyrosinyl
      radicals, which can lead to conformational change of beta-amyloid. The C1s band
      at 292.2eV suggests the formation of free carboxylic acid. The loss in the
      crucial structure of beta-amyloid leads to reduce the fibril formation, thought
      to be induced through a photocatalytic process. 

PMID- 24863221
TI  - Green synthesis of a new gelatin-based antimicrobial scaffold for tissue
      engineering.
AB  - With the aim of developing appropriate scaffolds for tissue engineering to
      suppress the formation of biofilms, an effective one-pot process was applied in
      this study to produce scaffolds with inherent antibacterial activity. A new
      method to synthesize genipin-crosslinked gelatin/nanosilver scaffolds with
      "green" in situ formation of silver nanoparticles by heat treatment is presented
      in this paper. In this procedure, toxic solvents, reducing agents, and
      stabilizing agents are avoided. UV-visible absorption spectra of the synthesized
      gelatin/nanosilver solutions were obtained immediately and three months after the
      synthesis revealing the presence and high stability of the silver nanoparticles.
      The TEM of gelatin/nanosilver solutions showed silver particles with spherical
      shapes that were less than 5nm in size. Interestingly, contact angle was found to
      increase from 80 degrees  to 125 degrees  with the increase in concentration of
      nanosilver in gelatin. All gelatin/nanosilver solutions showed antimicrobial
      activity against Staphylococcus aureus and Escherichia coli. However, only the
      highest concentration showed antifungal effects against Candida albicans
      pathogens. Scaffolds were prepared by a lyophilization technique from this
      solution and their antimicrobial activities were examined. Introducing this
      facile green one-pot process of synthesizing scaffolds with antimicrobial and
      anti-biofilm properties may lead to key applications in tissue engineering
      techniques. 

PMID- 24863222
TI  - Behaviors of MC3T3-E1 cells on carbonated apatite films, with a characteristic
      network structure, fabricated on a titanium plate by aqueous spray coating.
AB  - Four carbonated apatite films having average thicknesses of 1.3-0.11MUm,
      proportions of network sizes above 10MUm of 41-68%, and average border heights of
      the characteristic network structure of 0.98-0.29MUm were fabricated on a
      titanium plate by aqueous spray coating. These carbonated apatite films after
      heat treatment showed good mineralization ability in Hanks' balanced salt
      solution. Assessment of initial cell attachment and calcination on these films
      and on the Ti plate using osteoblastic MC3T3-E1 indicated that the carbonated
      apatite film heat treated at 600 degrees C, whose film thickness, proportion of
      network sizes above 10MUm, and border height were 0.11MUm, 61%, and 0.31MUm,
      respectively, was most preferred by osteoblastic cells. Field emission scanning
      electron microscopic observation of the cells attached to the films showed that
      the wide network and low border height of the network structure on the carbonated
      apatite film play an important role in the development of the filopodia of the
      osteoblastic cells. 

PMID- 24863223
TI  - An experimental-finite element analysis on the kinetic energy absorption capacity
      of polyvinyl alcohol sponge.
AB  - Polyvinyl alcohol (PVA) sponge is in widespread use for biomedical and tissue
      engineering applications owing to its biocompatibility, availability, relative
      cheapness, and excellent mechanical properties. This study reports a novel
      concept of design in energy absorbing materials which consist in the use of PVA
      sponge as an alternative reinforcement material to enhance the energy loss of
      impact loads. An experimental study is carried out to measure the mechanical
      properties of the PVA sponge under uniaxial loading. The kinetic energy
      absorption capacity of the PVA sponge is computed by a hexahedral finite element
      (FE) model of the steel ball and bullet through the LS-DYNA code under impact
      load at three different thicknesses (5, 10, 15mm). The results show that a higher
      sponge thickness invokes a higher energy loss of the steel ball and bullet. The
      highest energy loss of the steel ball and bullet is observed for the thickest
      sponge with 160 and 35J, respectively. The most common type of traumatic brain
      injury in which the head subject to impact load causes the brain to move within
      the skull and consequently brain hemorrhaging. These results suggest the
      application of the PVA sponge as a great kinetic energy absorber material
      compared to commonly used expanded polystyrene foams (EPS) to absorb most of the
      impact energy and reduces the transmitted load. The results might have
      implications not only for understanding of the mechanical properties of PVA
      sponge but also for use as an alternative reinforcement material in helmet and
      packaging material design. 

PMID- 24863224
TI  - Surface characterisation of Ti-15Mo alloy modified by a PEO process in various
      suspensions.
AB  - This paper reports on the surface modification of a Ti-15Mo alloy by plasma
      electrolytic oxidation (PEO). This process was carried out in solutions of 0.1M
      Ca(H2PO2)2 with various concentrations of tricalcium phosphate (Ca3(PO4)2),
      wollastonite (CaSiO3), or silica (SiO2) using voltages of up to 350V. The surface
      microstructure (SEM, cross-section of coating), roughness and chemical
      composition (energy-dispersive X-ray spectroscopy, thin layer X-ray diffraction,
      X-ray photoelectron spectroscopy and Raman spectroscopy) of the porous oxide
      layers were investigated. The concentration of powder added to the solution
      changed the chemical composition and morphology of PEO coatings on the Ti-15Mo
      alloy surface. Calcium and phosphorous compounds were detected in the coatings
      formed on the substrate by the PEO process at 300V. 

PMID- 24863225
TI  - High-efficiency combinatorial approach as an effective tool for accelerating
      metallic biomaterials research and discovery.
AB  - A high-efficiency combinatorial approach has been applied to rapidly build the
      database of composition-dependent elastic modulus and hardness of the Ti-Ta and
      Ti-Zr-Ta systems. A diffusion multiple of the Ti-Zr-Ta system was manufactured,
      then annealed at 1173K for 1800h, and water quenched to room temperature.
      Extensive interdiffusion among Ti, Zr and Ta has taken place. Combining
      nanoindentation and electron probe micro-analysis (EPMA), the elastic modulus,
      hardness as well as composition across the diffusion multiple were determined.
      The composition/elastic modulus/hardness relationship of the Ti-Ta and Ti-Zr-Ta
      alloys has been obtained. It was found that the elastic modulus and hardness
      depend strongly on the Ta and Zr content. The result can be used to accelerate
      the discovery/development of bio-titanium alloys for different components in
      implant prosthesis. 

PMID- 24863226
TI  - Graphene-cyclodextrin-cytochrome c layered assembly with improved electron
      transfer rate and high supramolecular recognition capability.
AB  - This study aimed to develop a new graphene-based layered assembly, named graphene
      cyclodextrin-cytochrome c with improved electron transfer rate. This assembly has
      combined high conductivity of graphene nanosheets (GNs), selectively binding
      properties and electronegativity of cyclodextrins (CDs), as well as
      electropositivity of cytochrome c (Cyt c). This assembly can also mimic the
      confined environments of the intermembrane space of mitochondria. A beta
      cyclodextrin (beta-CD) functionalized GN (GN-CD) assembly was initially prepared
      by a simple wet-chemical strategy, i.e., in situ thermal reduction of graphene
      oxide with hydrazine hydrate in the presence of beta-CD. Cyt c was then
      intercalated to the GN-CD assembly to form a layered self-assembled structure, GN
      CD-Cyt c, through electrostatic interaction. Compared with GNs and GN-CD, GN-CD
      Cyt c assembly displayed improved electron transfer rate and high supramolecular
      recognition capability toward six probe molecules. 

PMID- 24863227
TI  - Graphene and carbon nanotube nanocomposite for gene transfection.
AB  - Graphene and carbon nanotube nanocomposite (GCN) was synthesised and applied in
      gene transfection of pIRES plasmid conjugated with green fluorescent protein
      (GFP) in NIH-3T3 and NG97 cell lines. The tips of the multi-walled carbon
      nanotubes (MWCNTs) were exfoliated by oxygen plasma etching, which is also known
      to attach oxygen content groups on the MWCNT surfaces, changing their
      hydrophobicity. The nanocomposite was characterised by high resolution scanning
      electron microscopy; energy-dispersive X-ray, Fourier transform infrared and
      Raman spectroscopies, as well as zeta potential and particle size analyses using
      dynamic light scattering. BET adsorption isotherms showed the GCN to have an
      effective surface area of 38.5m(2)/g. The GCN and pIRES plasmid conjugated with
      the GFP gene, forming pi-stacking when dispersed in water by magnetic stirring,
      resulting in a helical wrap. The measured zeta potential confirmed that the
      plasmid was connected to the nanocomposite. The NIH-3T3 and NG97 cell lines could
      phagocytize this wrap. The gene transfection was characterised by fluorescent
      protein produced in the cells and pictured by fluorescent microscopy. Before
      application, we studied GCN cell viability in NIH-3T3 and NG97 line cells using
      both MTT and Neutral Red uptake assays. Our results suggest that GCN has moderate
      stability behaviour as colloid solution and has great potential as a gene carrier
      agent in non-viral based therapy, with low cytotoxicity and good transfection
      efficiency. 

PMID- 24863228
TI  - Electrochemical and cellular behavior of ultrafine-grained titanium in vitro.
AB  - The electrochemical and cellular behavior of commercially pure titanium (CP-Ti)
      with both ultrafine-grained (UFG) and coarse-grained (CG) microstructure was
      evaluated in this study. Equal channel angular pressing was used to produce the
      UFG structure titanium. Polarization and electrochemical impedance tests were
      carried out in a simulated body fluid (SBF) at 37 degrees C. Cellular behaviors
      of samples were assessed using fibroblast cells. Results of the investigations
      illustrate the improvement of both corrosion and biological behavior of UFG CP-Ti
      in comparison with the CG counterpart. 

PMID- 24863229
TI  - The induction of maturation on dendritic cells by TiO2 and Fe(3)O(4)@TiO(2)
      nanoparticles via NF-kappaB signaling pathway.
AB  - Nanomaterials are increasingly used in many fields, including drug vectors and
      vaccine formulation. In this study, nano-TiO(2) and magnetic Fe(3)O(4)@TiO(2)
      were synthesized and their abilities to activate dendritic cells were
      investigated. The signaling pathway involved in their effects on the cellular
      functions was also explored. First, nano-TiO(2) and Fe(3)O(4)@TiO(2) were
      prepared with diameters of 82nm and 63nm, and zeta potentials of 41.5mV and
      30.2mV, respectively. The magnetic property of Fe(3)O(4)@TiO(2) was detected to
      be 12.9emu/g. Both kinds of nanoparticles were proved to have good
      biocompatibility in vitro. Second, the exposure of nano-TiO2 and
      Fe(3)O(4)@TiO(2)caused an increased expression of TNF-alpha, CD86 and CD80, and
      besides, Fe(3)O(4)@TiO(2)showed a certain up-regulation on MHC-II. The cellular
      uptake of Ovalbumin on BMDCs could be strongly improved by nano-TiO2 and
      Fe(3)O(4)@TiO(2)as detected via flow cytometer and confocal observation. Further
      investigation revealed that nano-TiO(2) and Fe(3)O(4)@TiO(2)significantly
      increased the NF-kappaB expression in the nucleus, indicating that the NF-kappaB
      signaling pathway was involved in the dendritic cell maturation. Our results
      suggested that nano-TiO(2) and Fe(3)O(4)@TiO(2)may function as a useful vector to
      promote vaccine delivery in immune cells, and Fe(3)O(4)@TiO(2)provided a
      possibility to deliver and track vaccines via its magnetofection.

PMID- 24863230
TI  - Friction stir processing of magnesium-nanohydroxyapatite composites with
      controlled in vitro degradation behavior.
AB  - Nano-hydroxyapatite (nHA) reinforced magnesium composite (Mg-nHA) was fabricated
      by friction stir processing (FSP). The effect of smaller grain size and the
      presence of nHA particles on controlling the degradation of magnesium were
      investigated. Grain refinement from 1500MUm to ~3.5MUm was observed after FSP. In
      vitro bioactivity studies by immersing the samples in supersaturated simulated
      body fluid (SBF 5*) indicate that the increased hydrophilicity and pronounced
      biomineralization are due to grain refinement and the presence of nHA in the
      composite respectively. Electrochemical test to assess the corrosion behavior
      also clearly showed the improved corrosion resistance due to grain refinement and
      enhanced biomineralization. Using MTT colorimetric assay, cytotoxicity study of
      the samples with rat skeletal muscle (L6) cells indicate marginal increase in
      cell viability of the FSP-Mg-nHA sample. The composite also showed good cell
      adhesion. 

PMID- 24863231
TI  - Antimicrobial behavior of Cu-bearing Zr-based bulk metallic glasses.
AB  - The antimicrobial behavior of Cu-bearing Zr-based bulk metallic glasses (BMGs)
      was investigated for the first time against the Gram positive bacterium
      Staphylococcus aureus to evaluate their potential applications in healthcare
      settings. Despite their lack of bacteria-killing effect under a relatively severe
      experimental setting of dynamic immersion, the biocidal potency of the two Zr
      based BMGs was demonstrated via a moist contact assay. There was a significant
      reduction in viable bacterial populations after 4h of contact on the Zr-based
      BMGs, which was evidenced by the pronounced reduction in viable bacterial
      populations. To understand the mechanism of cell death, a direct relationship was
      established between the killing efficiency and the ability of the substrate to
      release Cu ions. Findings in this study will direct the future design of
      antimicrobial BMGs with enhanced killing efficacy. 

PMID- 24863232
TI  - Influence of shot peening on corrosion properties of biocompatible magnesium
      alloy AZ31 coated by dicalcium phosphate dihydrate (DCPD).
AB  - Magnesium alloys are promising materials for biomedical applications because of
      many outstanding properties like biodegradation, bioactivity and their specific
      density and Young's modulus are closer to bone than the commonly used metallic
      implant materials. Unfortunately their fatigue properties and low corrosion
      resistance negatively influenced their application possibilities in the field of
      biomedicine. These problems could be diminished through appropriate surface
      treatments. This study evaluates the influence of a surface pre-treatment by shot
      peening and shot peening+coating on the corrosion properties of magnesium alloy
      AZ31. The dicalcium phosphate dihydrate coating (DCPD) was electrochemically
      deposited in a solution containing 0.1M Ca(NO3)2, 0.06M NH4H2PO4 and 10mL/L of
      H2O2. The effect of shot peening on the surface properties of magnesium alloy was
      evaluated by microhardness and surface roughness measurements. The influence of
      the shot peening and dicalcium phosphate dihydrate layer on the electrochemical
      characteristics of AZ31 magnesium alloy was evaluated by potentiodynamic
      measurements and electrochemical impedance spectroscopy in 0.9% NaCl solution at
      a temperature of 22+/-1 degrees C. The obtained results were analyzed by the
      Tafel-extrapolation method and equivalent circuit method. The results showed that
      the application of shot peening process followed by DCPD coating improves the
      properties of the AZ31 surface from corrosion and mechanical point of view. 

PMID- 24863233
TI  - Effect of hydroxyapatite particle size, morphology and crystallinity on
      proliferation of colon cancer HCT116 cells.
AB  - The aim of the present work is to chemically and physically characterize the
      synthesized Hydroxyapatite (HAp) micro and nanoparticles and to explore the
      inhibitory effect of nano-HAps on the in vitro growth of human colon cancerous
      cells HCT116. HAp powder was synthesized using three different routes to achieve
      micro and nanosized powders, with different morphologies and crystallinity. The
      synthesized powders were characterized using X-ray diffraction, FTIR spectroscopy
      and scanning electron microscope. The results showed that the average crystallite
      size of HAp powder varies from 11nm to 177nm and respective crystallinity of
      powder found to be in the range of 0.12 and 0.92. The effect of these physico
      chemical properties of HAp powders on human colon cancer HCT116 cells inhibition
      was determined in vitro. It was found that decreasing the HAp powder crystallite
      size between 11nm and 22nm significantly increases the HCT116 cell inhibition.
      Our results demonstrate that apart from HAp powder size their crystallinity and
      morphology also play an important role in cellular inhibition of human colon
      cancer cells. 

PMID- 24863234
TI  - pH-responsive controlled release of epirubicin from Fe@Si-PW hybrid
      nanoparticles.
AB  - An efficient drug delivery system has been fabricated through an electrostatic
      interaction between epirubicin and H3PW12O40-functionalized silica encapsulated
      maghemite nanoparticles. The obtained nanoparticles were characterized for
      morphology, size distribution, drug loading efficiency, drug content and drug
      release behavior. Our results indicate that the hybrid nanoparticles possess high
      adsorption capacity for epirubicin (20.6wt.%) and high drug loading efficiency
      (82.6%). The drug release is greater in acetate buffer (95.8%) as compared to
      phosphate buffered saline (47.5%). The pH-responsive release of the hybrid drug
      carrier and high drug loading efficiency are its advantages as a promising
      carrier. 

PMID- 24863235
TI  - Influence of PCL on mechanical properties and bioactivity of ZrO2-based hybrid
      coatings synthesized by sol-gel dip coating technique.
AB  - The biological properties of medical implants can be enhanced through surface
      modifications such as to provide a firm attachment of the implant. In this study,
      organic-inorganic hybrid coatings have been synthesized via sol-gel dip coating.
      They consist of an inorganic ZrO2 matrix in which different amounts of
      poly(epsilon-caprolactone) have been entrapped to improve the mechanical
      properties of the films. The influence of the PCL amount on the microstructural,
      biological and mechanical properties of the coating has been investigated.
      Scanning electron microscopy (SEM) and X-ray diffraction (XRD) analyses have
      shown that the hybrids used for the coating are homogenous and totally amorphous
      materials; Fourier transform infrared spectroscopy (FT-IR) has demonstrated that
      hydrogen bonds arise between the organic and inorganic phases. SEM and atomic
      force microscopy (AFM) have highlighted the nanostructured nature of the film.
      SEM and EDS analyses, after soaking the samples in a simulated body fluid (SBF),
      have pointed out the apatite formation on the coating surface, which proves the
      bone-bonding ability of the nanocomposite bioactive films. Scratch and nano
      indentation tests have shown that the coating hardness, stiffness and Young's
      modulus decrease in the presence of large amounts of the organic phase. 

PMID- 24863236
TI  - Facile in situ synthesis of hydrophilic RGO-CD-Ag supramolecular hybrid and its
      enhanced antibacterial properties.
AB  - In this study, a novel hydrophilic RGO-CD-Ag hybrid with the supramolecular beta
      cyclodextrin (CD) as a conjugation interface was fabricated successfully by a
      facile in situ synthesis process. The results of several characterizations
      confirmed that the in situ reaction provided a straightforward approach to
      deposit the CD wrapped Ag nanoparticles onto the CD chemical functionalized RGO
      sheets through the head-to-head H-bond interactions between the linker CD
      molecules. Moreover, it was also found that the CD interface that existed indeed
      influences the structure and performances of RGO-CD-Ag nanocomposite. The
      analysis of the static contact angle revealed that the surface property of the
      hybrid could be transformed from hydrophobic to hydrophilic feature, which highly
      improved the aqueous dispersibility. And then, the bactericidal test of RGO-CD-Ag
      was demonstrated and clearly showed the strongest antibacterial activity against
      Gram-negative and Gram-positive bacteria among all samples. In short, this method
      may readily provide a new family of supramolecular based materials expected to
      find applications beyond the bactericidal field. 

PMID- 24863237
TI  - Carbon nanoparticles for gene transfection in eukaryotic cell lines.
AB  - For the first time, oxygen terminated cellulose carbon nanoparticles (CCN) was
      synthesised and applied in gene transfection of pIRES plasmid. The CCN was
      prepared from catalytic of polyaniline by chemical vapour deposition techniques.
      This plasmid contains one gene that encodes the green fluorescent protein (GFP)
      in eukaryotic cells, making them fluorescent. This new nanomaterial and pIRES
      plasmid formed pi-stacking when dispersed in water by magnetic stirring. The
      frequencies shift in zeta potential confirmed the plasmid strongly connects to
      the nanomaterial. In vitro tests found that this conjugation was phagocytised by
      NG97, NIH-3T3 and A549 cell lines making them fluorescent, which was visualised
      by fluorescent microscopy. Before the transfection test, we studied CCN in cell
      viability. Both MTT and Neutral Red uptake tests were carried out using NG97, NIH
      3T3 and A549 cell lines. Further, we use metabolomics to verify if small amounts
      of nanomaterial would be enough to cause some cellular damage in NG97 cells. We
      showed two mechanisms of action by CCN-DNA complex, producing an exogenous
      protein by the transfected cell and metabolomic changes that contributed by
      better understanding of glioblastoma, being the major finding of this work. Our
      results suggested that this nanomaterial has great potential as a gene carrier
      agent in non-viral based therapy, with low cytotoxicity, good transfection
      efficiency, and low cell damage in small amounts of nanomaterials in metabolomic
      tests. 

PMID- 24863238
TI  - Innovative surface modification of Ti-6Al-4V alloy with a positive effect on
      osteoblast proliferation and fatigue performance.
AB  - A novel approach of surface treatment of orthopaedic implants combining electric
      discharge machining (EDM), chemical milling (etching) and shot peening is
      presented in this study. Each of the three techniques have been used or proposed
      to be used as a favourable surface treatment of biomedical titanium alloys. But
      to our knowledge, the three techniques have not yet been used in combination.
      Surface morphology and chemistry were studied by scanning electron microscopy and
      X-ray photoelectron spectroscopy, respectively. Fatigue life of the material was
      determined and finally several in-vitro biocompatibility tests have been
      performed. EDM and subsequent chemical milling leads to a significant improvement
      of osteoblast proliferation and viability thanks to favourable surface morphology
      and increased oxygen content on the surface. Subsequent shot-peening
      significantly improves the fatigue endurance of the material. Material after
      proposed combined surface treatment possesses favourable mechanical properties
      and enhanced osteoblast proliferation. EDM treatment and EDM with shot peening
      also supported early osteogenic cell differentiation, manifested by a higher
      expression of collagen type I. The combined surface treatment is therefore
      promising for a range of applications in orthopaedics. 

PMID- 24863239
TI  - Effects of temperature, packaging and electron beam irradiation processing
      conditions on the property behaviour of Poly (ether-block-amide) blends.
AB  - The radiation stability of Poly (ether-block-amide) (PEBA) blended with a
      multifunctional phenolic antioxidant and a hindered amide light stabiliser was
      examined under various temperatures, packaging and electron beam processing
      conditions. FTIR revealed that there were slight alterations to the PEBA before
      irradiation; however, these became more pronounced following irradiation. The
      effect of varying the temperature, packaging and processing conditions on the
      resultant PEBA properties was apparent. For example, rheology demonstrated that
      the structural properties could be enhanced by manipulating the aforementioned
      criteria. Mechanical testing exhibited less radiation resistance when the PEBA
      samples were vacuum packed and exposed to irradiation. MFI and AFM confirmed that
      the melting strength and surface topography could be reduced/increased depending
      on the conditions employed. From this study it was concluded that virgin PEBA
      submerged in dry ice with non-vacuum packaging during the irradiation process,
      provided excellent radiation resistance (20.9% improvement) in contrast to the
      traditional method. 

PMID- 24863240
TI  - Are lithium niobate (LiNbO3) and lithium tantalate (LiTaO3) ferroelectrics
      bioactive?
AB  - The use of functional materials, such as ferroelectrics, as platforms for tissue
      growth in situ or ex situ, is new and holds great promise. But the usage of
      materials in any bioapplication requires information on biocompatibility and
      desirably on bioactive behavior when bone tissue engineering is envisaged. Both
      requirements are currently unknown for many ferroelectrics. Herein the
      bioactivity of LiNbO3 and LiTaO3 is reported. The formation of apatite-like
      structures on the surface of LiNbO3 and LiTaO3 powders after immersion in
      simulated body fluid (SBF) for different soaking periods indicates their
      bioactive potential. The mechanism of apatite formation is suggested. In
      addition, the significant release of lithium ions from the ferroelectric powders
      in the very first minutes of soaking in SBF is examined and ways to overcome this
      likely hurdle addressed. 

PMID- 24863241
TI  - Application of glass particles doped by Zn(+2) as an antimicrobial and atoxic
      compound in LLDPE and HDPE.
AB  - This study demonstrates the potential application of glass particles doped with
      Zn(+2) (GZn) as an atoxic, antimicrobial additive when used in conjunction with
      high density polyethylene (HDPE) and linear low density polyethylene (LLDPE)
      polymers. Toxicity tests demonstrated that these modified glass particles were
      nontoxic to human cells, and atomic absorption analyses demonstrated the
      migration of ionic species in quantities less than 2.0ppm for both the HDPE/GZn
      and LLDPE/GZn compounds. Microbiological tests demonstrated the antimicrobial
      effect of the pure GZn compound as well as the polymeric HDPE/GZn and LLDPE/GZn
      compounds. In addition, at percentages of GZn higher than 2.00wt.% and at a time
      of 4h, the bactericidal performance is excellent and equal for both polymeric
      compounds. 

PMID- 24863243
TI  - Total synthesis of the congested propellane alkaloid (-)-acutumine.
AB  - The enantioselective total synthesis of (-)-acutumine is described. The synthetic
      strategy was inspired by the premise that the cyclohexenone ring could be derived
      from an aromatic precursor. After successful construction of a propellane model
      system, an initial attempt to prepare the spirocyclic subunit was thwarted by
      incorrect regioselectivity in a radical cyclization. A second-generation approach
      involving a radical-polar crossover reaction was successful, and the chemistry
      developed in the aforementioned model system was then applied to synthesize the
      natural product. Key reactions included a phenolic oxidation, a
      diastereoselective ketone allylation utilizing Nakamura's chiral allylzinc
      reagent, an anionic oxy-Cope rearrangement, an acid-promoted cyclization of a
      secondary amine onto an alpha,beta-unsaturated ketal, and a regioselective methyl
      enol etherification of a 1,3-diketone. 

PMID- 24863242
TI  - A genomics approach identifies senescence-specific gene expression regulation.
AB  - Replicative senescence is a fundamental tumor-suppressive mechanism triggered by
      telomere erosion that results in a permanent cell cycle arrest. To understand the
      impact of telomere shortening on gene expression, we analyzed the transcriptome
      of diploid human fibroblasts as they progressed toward and entered into
      senescence. We distinguished novel transcription regulation due to replicative
      senescence by comparing senescence-specific expression profiles to profiles from
      cells arrested by DNA damage or serum starvation. Only a small specific subset of
      genes was identified that was truly senescence-regulated and changes in gene
      expression were exacerbated from presenescent to senescent cells. The majority of
      gene expression regulation in replicative senescence was shown to occur due to
      telomere shortening, as exogenous telomerase activity reverted most of these
      changes. 

PMID- 24863244
TI  - Predictors of article impact in suicidology: the bereavement literature, a
      research note.
AB  - Citation analysis has been neglected in suicidology. The present note applies a
      mixed-methods approach to both test and suggest hypotheses for the variation in
      article impact in the bereavement literature. One hundred three articles from
      three core suicidology journals met the criteria for inclusion in the
      investigation. Citations to the articles were obtained from the Web of Science.
      Predictor variables included structural characteristics of the author (e.g.,
      gender) and the article itself (e.g., years since publication). A multivariate
      regression analysis determined that, controlling for the other variables, the
      most important predictor of citations was the review article (beta = .461),
      followed by year of publication (beta = -.414), the multiauthored article (beta =
      .302), publication in Suicide and Life-Threatening Behavior (SLTB) (beta = .161),
      and male gender (beta = .156). The 12 most cited articles were published between
      1979 and 2004 in SLTB. The majority of these papers was written by males, were
      U.S. authors, and had more than one author. Four of the most cited articles were
      reviews. The study concludes that structural characteristics of articles and
      authors explained 41% of the variance in citations. The qualitative analysis
      determined that review papers, and papers on characteristics of suicide
      bereavement and psychological autopsies have been most frequently cited.
      Replication studies are needed for other subfields of suicidology.

PMID- 24863245
TI  - Reproductive and possible hormonal effects of carbendazim.
AB  - This study aimed to better elucidate reproductive and possible hormonal effects
      of the fungicide carbendazim (CBZ) through a review of published toxicological
      studies as well as an evaluation of this fungicide in the Hershberger and
      uterotrophic assays, which are designed to detect in vivo effects of the sex
      hormones. The literature review indicates that CBZ induces reproductive and
      developmental toxicity through alteration of many key events which are important
      to spermatogenesis. The lower dose of CBZ (100mg/kg) evaluated in the Hershberger
      test increased prostate weight compared to control group but did not alter the
      weight of other testosterone-dependent tissues. In the uterotrophic assay, CBZ
      did not induce an estrogenic or an antiestrogenic effect. In the literature, it
      has been reported that CBZ may: (1) alter the levels of various hormones
      (testosterone, LH, FSH, GnRH); (2) negatively influence testicular
      steroidogenesis; (3) have androgenic effects acting directly in the androgenic
      receptors and/or increasing the expression of androgen receptors. Despite the
      contradictory results reported by the different studies that investigated a
      possible endocrine mode of action of CBZ, it seems that this fungicide may
      influence the hypothalamus-pituitary-gonad axis in addition to being a testicular
      toxicant.

PMID- 24863246
TI  - From biomarker development towards implementation of multidimensional biomarker
      panels in a clinical setting.

PMID- 24863249
TI  - Unusual interval plot in a patient with a dual-chamber implantable cardioverter
      defibrillator.

PMID- 24863247
TI  - Necrotizing sialometaplasia-like change of the esophageal submucosal glands is
      associated with Barrett's esophagus.
AB  - The esophageal submucosal glands (SMG) protect the squamous epithelium from
      insults such as gastroesophageal reflux disease by secreting mucins and
      bicarbonate. We have observed metaplastic changes within the SMG acini that we
      have termed oncocytic glandular metaplasia (OGM), and necrotizing sialometaplasia
      like change (NSMLC). The aim of this study is to evaluate the associated
      clinicopathological parameters of, and to phenotypically characterize the SMG
      metaplasias. Esophagectomy specimens were retrospectively assessed on hematoxylin
      and eosin sections and assigned to either a Barrett's esophagus (BE) or non-BE
      control group. Clinicopathologic data was collected, and univariate analysis and
      multivariate logistic regression models were performed to assess the adjusted
      associations with NSMLC and OGM. Selected cases of SMG metaplasia were
      characterized. SMG were present in 82 esophagi that met inclusion criteria. On
      univariate analysis, NSMLC was associated with BE (p = 0.002). There was no
      relationship between NSMLC and patient age, sex, tumor size, or treatment
      history. OGM was associated with BE (p = 0.031). No relationship was found
      between OGM and patient age, sex, or tumor size. On multivariate analysis, BE was
      independently associated with NSMLC (odds ratio [OR] 4.95, p = 0.003). Treatment
      history was also independently associated with OGM (p = 0.029), but not NSMLC.
      Both NSMLC and OGM were non-mucinous ductal type epithelia retaining a p63-smooth
      muscle actin co-positive myoepithelial cell layer. NSMLC and OGM were present in
      endoscopic mucosal resection specimens. Our study suggests that SMG metaplasia is
      primarily a reflux-induced pathology. NSMLC may pose diagnostic dilemmas in
      resection specimens or when only partially represented in mucosal biopsies or
      endoscopic resection specimens.

PMID- 24863250
TI  - Liquid human milk fortifier significantly improves docosahexaenoic and
      arachidonic acid status in preterm infants.
AB  - We report the fatty acid composition of mother's own human milk from one of the
      largest US cohorts of lactating mothers of preterm infants. Milk fatty acid data
      were used as a proxy for intake at enrollment in infants (n=150) who received
      human milk with a powder human milk fortifier (HMF; Control) or liquid HMF [LHMF;
      provided additional 12mg docosahexaenoic acid (DHA), 20mg arachidonic acid
      (ARA)/100mL human milk]. Mothers provided milk samples (n=129) and reported
      maternal DHA consumption (n=128). Infant blood samples were drawn at study
      completion (Study Day 28). Human milk and infant PPL fatty acids were analyzed
      using capillary column gas chromatography. DHA and ARA were within ranges
      previously published for US term and preterm human milk. Compared to Control HMF
      (providing no DHA or ARA), human milk fortified with LHMF significantly increased
      infant PPL DHA and ARA and improved preterm infant DHA and ARA status. 

PMID- 24863251
TI  - Visual object agnosia is associated with a breakdown of object-selective
      responses in the lateral occipital cortex.
AB  - Patients with visual object agnosia fail to recognize the identity of visually
      presented objects despite preserved semantic knowledge. Object agnosia may result
      from damage to visual cortex lying close to or overlapping with the lateral
      occipital complex (LOC), a brain region that exhibits selectivity to the shape of
      visually presented objects. Despite this anatomical overlap the relationship
      between shape processing in the LOC and shape representations in object agnosia
      is unknown. We studied a patient with object agnosia following isolated damage to
      the left occipito-temporal cortex overlapping with the LOC. The patient showed
      intact processing of object structure, yet often made identification errors that
      were mainly based on the global visual similarity between objects. Using
      functional Magnetic Resonance Imaging (fMRI) we found that the damaged as well as
      the contralateral, structurally intact right LOC failed to show any object
      selective fMRI activity, though the latter retained selectivity for faces. Thus,
      unilateral damage to the left LOC led to a bilateral breakdown of neural
      responses to a specific stimulus class (objects and artefacts) while preserving
      the response to a different stimulus class (faces). These findings indicate that
      representations of structure necessary for the identification of objects
      crucially rely on bilateral, distributed coding of shape features. 

PMID- 24863252
TI  - Acute and chronic effects of kisspeptin-54 administration on GH, prolactin and
      TSH secretion in healthy women.
AB  - BACKGROUND: The peptide hormone kisspeptin is essential for human reproduction,
      acting on the hypothalamus to stimulate gonadotrophin-releasing hormone (GnRH)
      secretion. Kisspeptin is currently being evaluated as a novel therapeutic for
      women with infertility. However, some animal studies suggest that kisspeptin may
      also stimulate growth hormone (GH), prolactin and thyroid-stimulating hormone
      (TSH) secretion, with implications for its safety; no previous study has
      investigated whether kisspeptin stimulates these pituitary hormones in humans.
      AIM: To determine whether kisspeptin-54 modulates GH, prolactin and TSH secretion
      in healthy women. DESIGN AND PARTICIPANTS: Prospective, single-blinded, placebo
      controlled, one-way crossover study. Five healthy women received 7 days of twice
      daily subcutaneous bolus vehicle (month 1) or 6.4 nmol/kg kisspeptin-54 (month
      2). MEASUREMENTS: Serum samples were analysed post hoc for GH, prolactin and TSH.
      RESULTS: Mean serum GH, PRL and TSH did not change during the first 4 h following
      kisspeptin-54 injection when compared with vehicle. The mean frequency or
      amplitude of GH pulses (which influence GH function) did not change acutely
      following kisspeptin-54 injection when compared with vehicle. No chronic changes
      in serum GH, PRL or TSH were observed over the 7-day period of twice-daily
      kisspeptin-54 injections when compared with vehicle. CONCLUSION: While we cannot
      exclude any effect of kisspeptin-54 on GH, prolactin or TSH secretion, we
      observed no significant changes in these hormones at a dose of kisspeptin-54
      administration known to stimulate gonadotrophin secretion in a small study of
      healthy women. These data have important implications for the potential of
      kisspeptin to treat patients with infertility.

PMID- 24863253
TI  - The skin microbiome of caspase-14-deficient mice shows mild dysbiosis.
AB  - Caspase-14, an important proteinase involved in filaggrin catabolism, is mainly
      active in terminally differentiating keratinocytes, where it is required for the
      generation of skin natural moisturizing factors (NMFs). Consequently, caspase-14
      deficient epidermis is characterized by reduced levels of NMFs such as urocanic
      acid and 2-pyrrolidone-5-carboxylic acid. Patients suffering from filaggrin
      deficiency are prone to develop atopic dermatitis, which is accompanied with
      increased microbial burden. Among several reasons, this effect could be due to a
      decrease in filaggrin breakdown products. In this study, we found that caspase
      14(-/-) mice show enhanced antibacterial response compared to wild-type mice when
      challenged with bacteria. Therefore, we compared the microbial communities
      between wild-type and caspase-14(-/-) mice by sequencing of bacterial 16S
      ribosomal RNA genes. We observed that caspase-14 ablation leads to an increase in
      bacterial richness and diversity during steady-state conditions. Although both
      wild-type and caspase-14(-/-) skin were dominated by the Firmicutes phylum, the
      Staphylococcaceae family was reduced in caspase-14(-/-) mice. Altogether, our
      data demonstrated that caspase-14 deficiency causes the imbalance of the skin
      resident bacterial communities. 

PMID- 24863254
TI  - Rituximab is not useful in bilateral ocular involvement caused by eosinophilic
      granulomatosis with polyangiitis.

PMID- 24863255
TI  - Effect of botanicals on inflammation and skin aging: analyzing the evidence.
AB  - The skin and its immune system manifest a decline in physiologic function as it
      undergoes aging. External insults such as ultraviolet light exposure cause
      inflammation, which may enhance skin aging even further leading to cancer and
      signs of photoaging. There is a potential role for botanicals as an adjunct
      modality in the prevention of skin aging. Numerous over-the-counter anti-aging
      products are commercially available, many of which boast unverified claims to
      reduce stress, inflammation and correct signs of aging. In this article we
      reviewed the scientific literature for data on frequently published "anti
      inflammaging" additives such as vitamins A, C and E and green tea. We also
      analyzed the evidence available on five promising ingredients commonly found in
      anti-aging products, namely, argan oil, rosemary, pomegranate, Coenzyme Q10, and
      Coffeeberry. Though there may be an increasing amount of scientific data on a few
      of these novel botanicals, in general, there remains a lack of clinical data to
      support the anti-aging claims made.

PMID- 24863256
TI  - Cardiac and muscular involvement in idiopathic inflammatory myopathies:
      noninvasive diagnostic assessment and the role of cardiovascular and skeletal
      magnetic resonance imaging.
AB  - Idiopathic inflammatory myopathies (IIMs) are rare autoimmune diseases and
      include dermatomyositis, polymyositis, necrotizing myopathy and inclusion body
      myositis; they are characterized by inflammation of skeletal muscle and other
      internal organs and may potentially lead to irreversible damage and death. Only a
      small percentage of IIM has clinically overt cardiac disease; however, heart
      involvement is one of the leading causes of death and therefore, early detection
      remains a challenge. Biochemical markers and non-invasive methods such as the
      electrocardiogram and echocardiography have a role in diagnosis, but lack
      sensitivity in identifying patients with early, sublinical cardiac abnormalities.
      Endomyocardial and skeletal muscle biopsies are very useful, but invasive
      techniques and cannot be used for routine follow-up. Cardiac and skeletal
      magnetic resonance imaging, due to their capability to perform tissue
      characterization, has emerged as novel techniques for the early detection and
      follow-up of myocardial and skeletal muscle tissue changes (oedema, inflammation,
      fibrosis) in IIM. However, the clinical implications of using these approaches
      and their cost /benefit ratio require further evaluation. 

PMID- 24863257
TI  - New insight into active muscarinic receptors with the novel radioagonist
      [3H]iperoxo.
AB  - Activation of G protein-coupled receptors involves major conformational changes
      of the receptor protein ranging from the extracellular transmitter binding site
      to the intracellular G protein binding surface. GPCRs such as the muscarinic
      acetylcholine receptors are commonly probed with radioantagonists rather than
      radioagonists due to better physicochemical stability, higher affinity, and
      indifference towards receptor coupling states of the former. Here we introduce
      tritiated iperoxo, a superagonist at muscarinic M2 receptors with very high
      affinity. In membrane suspensions of transfected CHO-cells, [3H]iperoxo - unlike
      the common radioagonists [3H]acetylcholine and [3H]oxotremorine M - allowed
      labelling of each of the five muscarinic receptor subtypes in radioagonist
      displacement and saturation binding studies. [3H]iperoxo revealed considerable
      differences in affinity between the even- and the odd-numbered muscarinic
      receptor subtypes with affinities for the M2 and M4 receptor in the picomolar
      range. Probing ternary complex formation on the M2 receptor, [3H]iperoxo
      dissociation was not influenced by an archetypal allosteric inverse agonist,
      reflecting activation-related rearrangement of the extracellular loop region. At
      the inner side of M2, the preferred Gi protein acted as a positive allosteric
      modulator of [3H]iperoxo binding, whereas Gs and Gq were neutral in spite of
      their robust coupling to the activated receptor. In intact CHO-hM2 cells,
      endogenous guanylnucleotides promoted receptor/G protein-dissociation resulting
      in low-affinity agonist binding which, nevertheless, was still reported by
      [3H]iperoxo. Taken together, the muscarinic superagonist [3H]iperoxo is the best
      tool currently available for direct probing activation-related conformational
      transitions of muscarinic receptors.

PMID- 24863258
TI  - Cell type-specific recycling of tetrahydrobiopterin by dihydrofolate reductase
      explains differential effects of 7,8-dihydrobiopterin on endothelial nitric oxide
      synthase uncoupling.
AB  - (6R)-5,6,7,8-Tetrahydro-L-biopterin (BH4) availability regulates nitric oxide and
      superoxide formation by endothelial nitric oxide synthase (eNOS). At low BH4 or
      low BH4 to 7,8-dihydrobiopterin (BH2) ratios the enzyme becomes uncoupled and
      generates superoxide at the expense of NO. We studied the effects of exogenously
      added BH2 on intracellular BH4/BH2 ratios and eNOS activity in different types of
      endothelial cells. Incubation of porcine aortic endothelial cells with BH2
      increased BH4/BH2 ratios from 8.4 (controls) and 0.5 (BH4-depleted cells) up to
      ~20, demonstrating efficient reduction of BH2. Uncoupled eNOS activity observed
      in BH4-depleted cells was prevented by preincubation with BH2. Recycling of BH4
      was much less efficient in human endothelial cells isolated from umbilical veins
      or derived from dermal microvessels (HMEC-1 cells), which exhibited eNOS
      uncoupling and low BH4/BH2 ratios under basal conditions and responded to
      exogenous BH2 with only moderate increases in BH4/BH2 ratios. The kinetics of
      dihydrofolate reductase-catalyzed BH4 recycling in endothelial cytosols showed
      that the apparent BH2 affinity of the enzyme was 50- to 300-fold higher in
      porcine than in human cell preparations. Thus, the differential regulation of
      eNOS uncoupling in different types of endothelial cells may be explained by
      striking differences in the apparent BH2 affinity of dihydrofolate reductase.

PMID- 24863259
TI  - Targeting PI3K/AKT/mTOR pathway in non small cell lung cancer.
AB  - While PI3K/AKT/mTOR pathway is altered in a variety of cancers including non
      small cell lung cancer, abnormalities in this pathway are more common in squamous
      cell lung carcinoma than in adenocarcinoma of the lung. Moreover, aberrant
      activation of PI3K/AKT/mTOR pathway is one of the mechanisms of acquired
      resistance to EGFR-TK inhibitors in patients with adenocarcinoma carrying EGFR
      activating mutations. Several inhibitors of the PI3K pathway are undergoing
      evaluation in preclinical and clinical studies. These include pan and selective
      inhibitors of PI3K, AKT inhibitors, rapamycin and rapalogs for mTOR inhibition,
      dual mTORC1-mTORC2 inhibitors and dual PI3K-mTOR inhibitors. This review focuses
      on recent preclinical and clinical data on the efficacy of PI3K pathway
      inhibitors in NSCLC either as monotherapy approach or in combination with
      chemotherapy or with drugs that target other signaling transduction pathways.

PMID- 24863260
TI  - Relationship between diclofenac dose and risk of gastrointestinal and
      cardiovascular events: meta-regression based on two systematic literature
      reviews.
AB  - BACKGROUND: NSAIDs are associated with risks of gastrointestinal (GI) and
      cardiovascular (CV) toxicities. It has been reported that the risks of GI and CV
      events are dose related, resulting in guidance explicitly emphasizing the use of
      NSAIDs at the lowest effective dose for the shortest duration. To understand the
      potential benefits of using lower doses of diclofenac, a more detailed
      understanding of the relationship of diclofenac dose and the risks of GI and CV
      events is required. OBJECTIVE: The objective of this study was to extend previous
      research quantifying the NSAID dose-toxicity relationship by modeling dose as a
      continuous measure, allowing for an assessment of the risks of major GI and CV
      events for patients taking specific diclofenac doses compared with NSAID
      nonusers. METHODS: We used studies identified in 2 recently published systematic
      reviews of observational studies that examined the risks of major GI and CV
      events associated with the use of oral NSAIDs. We developed meta-regression
      models, considering dose as a continuous measure, to estimate the risks of major
      GI and CV events for different daily doses of conventional oral diclofenac
      relative to nonuse of NSAIDs. RESULTS: Seven of the 59 GI publications,
      contributing 11 dose-specific risk ratio observations, and 12 of the 51 CV
      studies, contributing 21 dose-specific risk ratio observations, were eligible for
      inclusion in the meta-regression. The models indicated positive linear
      relationships between diclofenac dose and the relative risks of major GI and CV
      events for the range of doses examined. CONCLUSIONS: To our knowledge, this is
      the first study to quantify and aggregate the continuous relationship between the
      risk of GI or CV events and the dosage of an NSAID. With the recent availability
      of new low doses of diclofenac, the models may be used to estimate the potential
      reduction in risk of adverse events at these doses.

PMID- 24863261
TI  - Exosomes as immunotheranostic nanoparticles.
AB  - BACKGROUND: Exosomes are small biological membrane vesicles that measure 30 to
      100 nm in diameter. They are involved in a wide array of biological activities,
      such as cell-cell communication, signal transduction, transport of genetic
      materials, and modulation of immune response. Evidence indicates that they can be
      used as not only therapeutic agents targeted against disease but also diagnostic
      biomarkers for pathologic conditions. OBJECTIVE: In this review, we endeavor to
      present exosomes as immunologic agents that can be used as pioneering cancer
      vaccines to prime the immune system and explicate their therapeutic and
      diagnostic capabilities. METHODS: An extensive literature search for studies that
      involved the use of exosomes as immunotheranostic nanoparticles was conducted
      using PubMed, ISI Web of Knowledge, and Google Scholar. Clinical trials that
      involved exosomes were also compiled by searching the clinicaltrials.gov
      database. RESULTS: In its therapeutic facet of application, exosomes can be used
      as vehicles for drug or gene delivery. These biological vesicles have been found
      to have excellent host biodistribution and biocompatibility, issues often
      presented with gene delivery vehicles. Diagnostically, exosomes may prove to be
      useful biomarkers that are able to surpass current setbacks of modern diagnostic
      testing, which include invasive methods. Finally, current evidence has implied
      that the use of exosomes could form the basis for the development of future cell
      free cancer vaccines. CONCLUSION: Exosomes have numerous functions, and their
      double-edged features make the scope of their clinical applications, as both a
      diagnostic and therapeutic tool, immense.

PMID- 24863262
TI  - Potential of cancer cell-derived exosomes in clinical application: a review of
      recent research advances.
AB  - BACKGROUND: Exosomes are 30- to 100-nm, membrane-bound vesicles that are released
      by most types of cells, including tumor cells. Exosomes contain a great variety
      of bioactive molecules, including signal peptides, microRNA, lipids, and DNA. In
      cancer, tumor cells aberrantly secrete large quantities of exosomes to transport
      paracrine signals or to contribute to tumor-environment interaction at a
      distance. OBJECTIVE: The goal of this review was to discuss the recent advances
      on the mechanism of cancer-derived exosomes in tumor regulation. METHODS:
      Pertinent articles and abstracts were identified through searches of PubMed for
      literature published from 1983 to December 2013. Search terms included exosome,
      tumor, cancer, diagnosis, and therapy. RESULTS: All of the exposed evidence
      points to communication between cancer cells and their surroundings, either
      mediated by cancer cell-derived exosomes or by stromal cell-derived exosomes.
      This communication probably supports tumor proliferation, motility, invasion,
      angiogenesis, and premetastatic niche preparation. In addition, recent research
      implies that cancer cell-derived exosomes play a suppressive role in cancer
      directed immune response. CONCLUSIONS: The biomarkers detected in bodily fluid
      derived exosomes imply a potential for exosomes in cancer diagnosis. Also,
      exosomes could be used as a vehicle to selectively deliver therapeutic nucleic
      acid drugs or conventional drugs for tumor therapy. The tolerability and
      feasibility of cancer exosomes in diagnosis and therapy need to be further
      evaluated.

PMID- 24863263
TI  - Respirable quartz dust exposure and airway obstruction: a systematic review and
      meta-analysis.
AB  - Studies on exposure to respirable quartz dust at the workplace and the
      development of chronic obstructive pulmonary disease (COPD) were selected into a
      systematic review and meta-analysed to obtain an overall estimate of forced
      expiratory volume in 1 s (FEV1) and FEV1/forced vital capacity (FVC) reduction.
      PubMed and Embase were searched from 1970 to 2010. In total, 257 cross-sectional
      and longitudinal studies were identified that reported on inorganic dust exposure
      and had available lung function data. Of the 55 publications which met our
      inclusion criteria, 11 reported on associations with occupational exposure to
      respirable quartz dust. The combined average effect estimate of respirable quartz
      dust on spirometric parameters was obtained using a random effects model meta
      analysis. Between-study heterogeneity was assessed via the I(2) statistic. Most
      studies found a significant negative association of FEV1 and FEV1/FVC related to
      increasing exposure to crystalline quartz at the workplace. One study found an
      effect only for smokers, and one did not observe such an effect at all. The meta
      analysis of cross-sectional studies showed that the mean ratio FEV1 to FVC was
      reduced and FEV1 of workers exposed to respirable quartz dust was 4.6% less than
      predicted compared with workers with no/low exposure. Both results showed a
      statistically significant difference. Occupational exposure to respirable quartz
      dust was associated with a statistically significant decrease in FEV1 and
      FEV1/FVC, revealing airway obstruction consistent with COPD.

PMID- 24863264
TI  - Quality of life depends on the drinking pattern in alcohol-dependent patients.
AB  - AIMS: In patients with alcohol dependence, health-related quality of life (QOL)
      is reduced compared with that of a normal healthy population. The objective of
      the current analysis was to describe the evolution of health-related QOL in
      adults with alcohol dependence during a 24-month period after initial assessment
      for alcohol-related treatment in a routine practice setting, and its relation to
      drinking pattern which was evaluated across clusters based on the predominant
      pattern of alcohol use, set against the influence of baseline variables METHODS:
      The Medical Outcomes Study 36-Item Short-Form Survey (MOS-SF-36) was used to
      measure QOL at baseline and quarterly for 2 years among participants in CONTROL,
      a prospective observational study of patients initiating treatment for alcohol
      dependence. The sample consisted of 160 adults with alcohol dependence (65.6%
      males) with a mean (SD) age of 45.6 (12.0) years. Alcohol use data were collected
      using TimeLine Follow-Back. Based on the participant's reported alcohol use,
      three clusters were identified: 52 (32.5%) mostly abstainers, 64 (40.0%) mostly
      moderate drinkers and 44 (27.5%) mostly heavy drinkers. Mixed-effect linear
      regression analysis was used to identify factors that were potentially associated
      with the mental and physical summary MOS-SF-36 scores at each time point.
      RESULTS: The mean (SD) MOS-SF-36 mental component summary score (range 0-100,
      norm 50) was 35.7 (13.6) at baseline [mostly abstainers: 40.4 (14.6); mostly
      moderate drinkers 35.6 (12.4); mostly heavy drinkers 30.1 (12.1)]. The score
      improved to 43.1 (13.4) at 3 months [mostly abstainers: 47.4 (12.3); mostly
      moderate drinkers 44.2 (12.7); mostly heavy drinkers 35.1 (12.9)], to 47.3 (11.4)
      at 12 months [mostly abstainers: 51.7 (9.7); mostly moderate drinkers 44.8
      (11.9); mostly heavy drinkers 44.1 (11.3)], and to 46.6 (11.1) at 24 months
      [mostly abstainers: 49.2 (11.6); mostly moderate drinkers 45.7 (11.9); mostly
      heavy drinkers 43.7 (8.8)]. Mixed-effect linear regression multivariate analyses
      indicated that there was a significant association between a lower 2-year follow
      up MOS-SF-36 mental score and being a mostly heavy drinker (-6.97, P < 0.001) or
      mostly moderate drinker (-3.34 points, P = 0.018) [compared to mostly
      abstainers], being female (-3.73, P = 0.004), and having a Beck Inventory scale
      score >=8 (-6.54, P < 0.001), at baseline. The mean (SD) MOS-SF-36 physical
      component summary score was 48.8 (10.6) at baseline, remained stable over the
      follow-up and did not differ across the three clusters. Mixed-effect linear
      regression univariate analyses found that the average 2-year follow-up MOS-SF-36
      physical score was increased (compared with mostly abstainers) in mostly heavy
      drinkers (+4.44, P = 0.007); no other variables tested influenced the MOS-SF-36
      physical score. CONCLUSION: Among individuals with alcohol dependence, a rapid
      improvement was seen in the mental dimension of QOL following treatment
      initiation, which was maintained during 24 months. Improvement was associated
      with the pattern of alcohol use, becoming close to the general population norm in
      patients classified as mostly abstainers, improving substantially in mostly
      moderate drinkers and improving only slightly in mostly heavy drinkers. The
      physical dimension of QOL was generally in the normal range but was not
      associated with drinking patterns.

PMID- 24863265
TI  - MOSAIC_SSD: a new web tool for species sensitivity distribution to include
      censored data by maximum likelihood.
AB  - Censored data are seldom taken into account in species sensitivity distribution
      (SSD) analysis. However, they are found in virtually every dataset and sometimes
      represent the better part of the data. Stringent recommendations on data quality
      often entail discarding a lot of these meaningful data, resulting in datasets of
      reduced size which lack representativeness of any realistic community. However,
      it is reasonably simple to include censored data in SSD by using an extension of
      the standard maximum likelihood method. The authors detail this approach based on
      the use of the R-package fitdistrplus, dedicated to the fit of parametric
      probability distributions. The authors present the new Web tool MOSAIC_SSD, that
      can fit an SSD on datasets containing any type of data, censored or not. The
      MOSAIC_SSD Web tool predicts any hazardous concentration and provides bootstrap
      confidence intervals on the predictions. Finally, the authors illustrate the
      added value of including censored data in SSD, taking examples from published
      data.

PMID- 24863266
TI  - Val66Met polymorphism in the BDNF gene in children with bronchial asthma.
AB  - OBJECTIVES: Bronchial asthma is a chronic respiratory disease characterized by
      airway inflammation. There is increasing evidence that neurotrophins play an
      important role in the development and maintenance of neurogenic airway
      inflammation in chronic allergic diseases. WORKING HYPOTHESIS: Brain-derived
      neurotrophic factor (BDNF) is a member of the neurotrophin family and has several
      important functions in the airways. There are only a few reports on the
      association between genetic variations in the BDNF gene and various allergic
      diseases, and the results are generally conflicting. Therefore, we aimed to study
      the functional polymorphism Val66Met (also called rs6265 or G196A) in the BDNF
      gene in a group of asthmatic children and healthy controls. STUDY DESIGN, PATIENT
      SELECTION, AND METHODOLOGY: We studied 248 asthmatic patients (aged 12.28 +/-
      0.24 years) and 249 healthy children (aged 13.14 +/- 0.48 years). Analysis of the
      Val66Met polymorphism of the BDNF gene was performed by polymerase chain reaction
      (PCR) and PCR products were digested by PmlI. RESULTS: The prevalence of the
      Val66Met polymorphisms (Val/Val, Val/Met, and Met/Met) was 61.7%, 33.5%, and 4.8%
      in asthmatics, respectively, and 47.0%, 51.8%, and 1.2% in healthy subjects,
      respectively. We observed a significant association of the Met/Met variant
      genotype with asthmatics (OR = 4.17, 95% CI = 1.16-14.96, P = 0.018). The Val/Met
      genotype was protective against bronchial asthma (OR = 0.69, 95% CI = 0.48-0.99,
      P = 0.045), especially in girls (OR = 0.34, 95% CI = 0.20-0.59, P = 0.001).
      CONCLUSION: Specific BDNF gene polymorphism may contribute to bronchial asthma
      susceptibility. Our study suggested the positive association between selected
      functional BDNF polymorphism (rs6265) and asthma in children.

PMID- 24863267
TI  - Incarceration medical problems.

PMID- 24863268
TI  - Overview of correctional medicine.

PMID- 24863269
TI  - Delivering HIV subspecialty care in prisons utilizing telemedicine.

PMID- 24863271
TI  - Mentally ill offenders impact on the prison system.

PMID- 24863270
TI  - Hepatitis C.

PMID- 24863273
TI  - Dental care in corrections.

PMID- 24863272
TI  - Suicide in corrections: an overview.

PMID- 24863274
TI  - Conclusion.

PMID- 24863276
TI  - Possible mechanisms of the antifungal activity of fluconazole in combination with
      terbinafine against Candida albicans.
AB  - CONTEXT: Candidiasis is a term describing infections by yeasts from the genus
      Candida, the majority Candida albicans. Treatment of such infections often
      requires antifungals such as the azoles, but increased use of these drugs has led
      to selection of yeasts with increased resistance to these drugs. OBJECTIVE:
      Combination therapy would be one of the best strategies for the treatment of
      candidiasis due to increased resistance to azoles. MATERIALS AND METHODS: The
      antifungal activities of fluconazole and terbinafine were evaluated in vitro
      alone and in combination using broth microdilution test and time kill study.
      Eventually the expression level of selected genes involved in ergosterol
      biosynthesis of Candida was evaluated using semi-quantitative RT-PCR. RESULTS:
      The obtained results showed the significant MICs ranging from 0.25 to 8 ug/mL
      followed by FICs ranged from 0.37 to 1 in combination with
      fluconazole/terbinafine. Our findings have demonstrated that the combination of
      fluconazole and terbinafine could also significantly reduce the expression of
      ERG1, 3, and 11 in the cell membrane of Candida in all concentrations tested
      ranging from 1.73- to 6.99-fold. DISCUSSION AND CONCLUSION: This study was
      undertaken with the ultimate goal of finding the probable targets of
      fluconazole/terbinafine in C. albicans by looking at its effects on cell membrane
      synthesis.

PMID- 24863277
TI  - In vitro antioxidant and antitumor activities of six selected plants used in the
      Traditional Arabic Palestinian herbal medicine.
AB  - CONTEXT: Despite several pharmacological applications of the medicinal plants in
      the Traditional Arabic Palestinian Herbal Medicine in Palestine (TAPHM), studies
      on their antioxidant properties are still scarce. OBJECTIVE: This work evaluates
      the antioxidant and antitumor activities of the ethanol extracts from different
      parts of six plants: [Arum palaestinum Boiss (Araceae), Urtica pilulifera L.
      (Urticaceae), Coridothymus capitatus (L.) Reichb (Lamiaceae), Majorana syriaca
      (L.) Rafin. (Lamiaceae), Teucrium creticum L. (Lamiaceae), and Teucrium capitatum
      L. (Lamiaceae)] used in the TAPHM. MATERIALS AND METHODS: The antioxidant
      activity was evaluated for the ethanol extracts by DPPH and beta-carotene
      linoleic acid assays together with total contents of phenols and flavonoids. For
      the anti-carcinogenic evaluation, the extracts were tested for the ability to
      inhibit the proliferation of breast cancer cells (MCF-7) using the MTT reduction
      assay. RESULTS: Among the extracts, the U. pilulifera had the highest amount of
      total phenolics, possessing the second highest total flavonoids. It also showed a
      maximum cytotoxic activity (IC50 = 63 ug/ml), followed by C. capitatus, and A.
      palaestinum. Otherwise, the extract of T. creticum was demonstrated to be an
      efficient scavenger of O2 (IC50 = 83 ug/ml), followed by M. syriaca, C.
      capitatus, T. capitatum, A. palaestinum, and U. pilulifera. DISCUSSION AND
      CONCLUSION: The results suggest that the investigated plants have shown varied
      antioxidant capacities which were strongly correlated with their contents of
      phenolics. Accordingly, this study proposes that the therapeutic benefit of these
      plants can be, at least in part, attributed to its potential inhibition of
      oxidative processes.

PMID- 24863278
TI  - In vitro evaluation of the antibacterial activity of extracts from 34 species of
      North American lichens.
AB  - CONTEXT: The emergence of antibiotic resistant pathogens is a serious global
      health threat. Hence, the search for new antibiotic drugs from various natural
      sources should be given high priority. Lichens produce a variety of low molecular
      weight metabolic compounds and many cultures have utilized these compounds in
      traditional medicine for centuries. OBJECTIVE: Report the antibiotic properties
      of extracts from 34 North American lichens screened against four pathogenic
      bacteria. MATERIALS AND METHODS: The micro-well dilution method was used to
      determine the minimum inhibitory concentration (MIC) of acetone and methanol
      extracts of 34 lichen species against four bacterial strains. Major chemical
      compounds in each species were identified using thin layer chromatography (TLC).
      RESULTS: Most of the lichen extracts demonstrated inhibitory effects against
      Staphylococcus aureus, Pseudomonas aeruginosa, and methicillin-resistant S.
      aureus (MRSA) with MIC values ranging from 3.9 to 500 ug/ml. In addition,
      extracts from three species, Letharia columbiana (Nutt.) J. W. Thomson
      (Parmeliaceae), Letharia vulpina (L.) Hue (Parmeliaceae), and Vulpicida
      canadensis (Rasanen) J.-E. Mattsson & M. J. Lai (Parmeliaceae) (MIC = 125-500
      ug/ml) were also effective against Escherichia coli. Generally, acetone
      extractions were found to be more effective than methanol extractions. DISCUSSION
      AND CONCLUSION: Results of this study show that lichen extracts provide
      significant antimicrobial activity against both Gram-positive and Gram-negative
      bacteria. These results suggest that lichens may be an important potential source
      of antibacterial drugs.

PMID- 24863279
TI  - Cytotoxic and antiproliferative constituents from Dictyota ciliolata, Padina
      sanctae-crucis and Turbinaria tricostata.
AB  - CONTEXT: The hexane extracts of Dictyota ciliolata Sonder ex Kutzing
      (Dictyotaceae), Padina sanctae-crucis Borgesen (Dictyotaceae), and Turbinaria
      tricostata E.S. Barton (Sargassaceae) were found to exhibit cytotoxic and
      antiproliferative activities in vitro. Bioactive compounds responsible for these
      activities have not been studied in detail for these species and phytochemical
      studies are very limited. OBJECTIVE: Isolate, evaluate, and elucidate the
      bioactive constituents of D. ciliolata, P. sanctae-crucis, and T. tricostata.
      MATERIALS AND METHODS: Bioassay-guided cytotoxicity fractionations using the Hep
      2 cell line of the hexane extracts from these brown algae were analyzed using
      various chromatographic techniques. Cytotoxic and antiproliferative activities of
      all isolated compounds were also evaluated on a panel of cell lines (KB, Hep-2,
      MCF-7, and SiHa). Furthermore, their selectivity index, the ratio of cytotoxicity
      on normal cells to cancer cells, was evaluated using the HEK-293 cell line.
      RESULTS: Four compounds were isolated from studied species: two sterol,
      fucosterol (1) and 24xi-hydroperoxy-24-vinylcholesterol (2); and two diterpenes,
      pachydictyol A (3) and dictyol B acetate (4). The major bioactive components of
      the hexane extracts of T. tricostata and P. sanctae-crucis were compounds 1 and 2
      (with CC50 varying around 3.1-25.6 ug/mL) on cell lines tested. Whereas compounds
      1, 3, and 4 showed cytotoxic activity against cancer cell lines (CC50 varying
      between 14.8 and 41.2 ug/mL) and were major bioactive constituents of hexane
      extract of D. ciliolata. Compounds 1 and 4 showed antiproliferative activity on
      MCF-7 (IC50 = 43.3 ug/mL for compound 1 and 38.3 ug/mL for compound 2) and SiHa
      (IC50 = 43.3 ug/mL for compound 1 and 38.3 ug/mL for compound 2) cell lines.
      CONCLUSION: This study is the first investigation on the bioactive components of
      D. ciliolata, P. sanctae-crucis, and T. tricostata. Although compounds 1-3 were
      described previously, the pharmacological activity of compound 4 is presented
      here for the first time.

PMID- 24863280
TI  - Chemical composition analysis of rose water samples from Iran.
AB  - CONTENT: Rosa damascena Mill. (Rosaceae) is an important ornamental and medicinal
      plant and a source of fragrance. Its hydrosol is known in Iran as golab (rose
      water) and has applications in religious ceremonies, food, and pharmaceuticals.
      Hydrosol is traditionally and industrially produced by distillation. The increase
      in market demand has led to production of inferior products for hydrosol that
      contain synthetic essences or essential oils of other plants, or that have been
      diluted with water. Inferior product often may be distinguished via its color
      changes and weak odor. However, details need to be determined by chemical
      analysis. OBJECTIVE: The current study evaluated the composition and quality of
      10 rose water samples purchased from local markets in Shiraz, capital of Fars
      province in Iran. MATERIALS AND METHODS: The essential oils of the samples were
      extracted and analyzed using gas chromatography-mass spectrometry. RESULTS:
      RESULTS revealed that phenethyl alcohol, geraniol, and beta-citronellol were the
      main constituents of most samples. In total, 22 constituents were detected and
      identified in the samples. Identification was determined for 60.97-96.07% of the
      essential oil components. DISCUSSION AND CONCLUSION: It was concluded that
      Pelargonium and Dianthus essential oils and synthetic essences had been added to
      some samples. Dibutyl phthalate was also detected in most samples. This
      substance, which commonly exists as polyethylene terephthalate, may have been
      released into the samples from their containers.

PMID- 24863281
TI  - Mucor fragilis as a novel source of the key pharmaceutical agents podophyllotoxin
      and kaempferol.
AB  - CONTEXT: Podophyllotoxin, a pharmaceutically important bioactive compound of
      Podophyllum sps. (Berberidaceae), is in great demand worldwide as an anticancer
      and antivirus drug precursor. However, the source of podophyllotoxin is very
      limited due to the endangered status of the Podophyllum plant. OBJECTIVE: The aim
      of this study was to isolate podophyllotoxin-producing endophytic fungi from
      Sinopodophyllum hexandrum (Royle) Ying (1979) (Berberidaceae) plants of the
      Taibai Mountains of China in order to obtain bioactive compounds. MATERIALS AND
      METHODS: The strains producing kaempferol and podophyllotoxin were screened by
      thin-layer chromatography (TLC) analysis. The presence of kaempferol and
      podophyllotoxin in extracts of these strains was further confirmed by high
      performance liquid chromatography (HPLC) and nuclear magnetic resonance (NMR)
      analyses. RESULTS: Among six endophytic fungi isolated from the rhizomes of S.
      hexandrum, one strain was able to produce kaempferol. Another strain, named TW5,
      was able to produce both kaempferol and podophyllotoxin simultaneously according
      to the TLC, HPLC, and NMR results. The podophyllotoxin yield of TW5 was
      calculated to be 49.3 MUg/g of mycelial dry weight after 7-d fermentation. Strain
      TW5 was identified morphologically and phylogenetically to be Mucor fragilis
      Fresen. (Mucoraceae). These results suggest that the podophyllotoxin-synthesizing
      ability is obtained by uptaking genes involved in the podophyllotoxin synthesis
      from the host plant into endophytic fungal genomes. CONCLUSION: Our results
      showed, for the first time, that the endophytic fungus M. fragilis is able to
      produce simultaneously the same two bioactive metabolites, podophyllotoxin and
      kaempferol, as its host plant. Furthermore, the relatively high podophyllotoxin
      yield obtained may improve the industrial production of podophyllotoxin, which
      may help protect this endangered plant.

PMID- 24863282
TI  - Cytotoxic effects of four Caryophyllaceae species extracts on macrophage cell
      lines.
AB  - CONTEXT: Saponins have been reported to possess antitumor properties, to inhibit
      angiogenesis and to induce tumor apoptosis. OBJECTIVE: To test the possible
      cytotoxic effect of crude extracts from four Caryophyllaceae species including
      Gypsophila paniculata L., Gypsophila trichotoma Wend., Saponaria officinalis L.,
      and Dianthus sylvestris Wulffen on cultured monocyte/macrophage cell lines.
      MATERIALS AND METHODS: After acid hydrolysis of the methanol-aqueous extracts,
      two representative prosaponins of the Caryophyllaceae, gypsogenin 3-O-glucuronide
      and quillaic acid 3-O-glucuronide were purified using solid-phase extraction
      (SPE), then identified by ultra-performance liquid chromatography
      electrospray/mass spectrometry (UPLC-ESI/MS). Cytotoxic activity of the crude
      extracts at concentrations ranging from 0.1 to 200 ug/ml was evaluated on rat
      alveolar macrophage NR8383 and human monocytic THP-1 cell lines. Apoptosis was
      determined by measuring caspase-3 activity. RESULTS: Quantitative analysis by
      reversed-phase high-performance liquid chromatography (RP-HPLC) revealed a high
      content of gypsogenin 3-O-glucuronide in Gypsophila species roots (0.52-1.13% dry
      weight). At a concentration >=10 ug/ml of crude extracts, a significant reduction
      of NR8383 and THP-1 cell lines viability was evidenced using the Trypan blue
      exclusion test. D. sylvestris extract exhibited the highest toxicity against THP
      1 cells. Caspase-3 activation was evidenced after 4 and 24 h incubation of
      macrophages with 100 ug/ml of S. officinalis and G. trichotoma extracts,
      indicating apoptosis induction. DISCUSSION AND CONCLUSION: Crude extracts from
      the assayed species revealed cytotoxic effects toward macrophage cell lines. In
      Gypsophila species, gypsogenin 3-O-glucuronide derivatives could be responsible
      for the observed cytotoxicity. Therefore, crude extract of Caryophyllaceae is
      worth investigating for the potential development of agents against cancer cells.

PMID- 24863283
TI  - Monoclonal surface display SELEX for simple, rapid, efficient, and cost-effective
      aptamer enrichment and identification.
AB  - A novel method, monoclonal surface display SELEX (MSD-SELEX), has been designed
      for simple, rapid, efficient, and cost-effective enrichment and identification of
      aptamers from a library of monoclonal DNA-displaying beads produced via highly
      parallel single-molecule emulsion PCR. The approach was successfully applied for
      the identification of high-affinity aptamers that bind specifically to different
      types of targets, including cancer biomarker protein EpCAM and small toxin
      molecule aflatoxin B1. Compared to the conventional sequencing-chemical synthesis
      screening work flow, MSD-SELEX avoids large-scale DNA sequencing, expensive and
      time-consuming DNA synthesis, and labor-intensive screening of large populations
      of candidates, thus offering a new approach for simple, rapid, efficient, and
      cost-effective aptamer identification for a wide variety of applications. 

PMID- 24863284
TI  - The patient-centeredness of endometriosis care and targets for improvement: a
      systematic review.
AB  - BACKGROUND: Endometriosis is a prevalent condition compromising physical and
      psychosocial health and thus requiring patient-centered care, which is guided by
      patients' values. This study aimed to find out what the patient's perspective on
      endometriosis care is and how the patient-centeredness of endometriosis care can
      be improved. METHODS: Electronic databases were searched systematically, and
      study selection was based on eligibility and quality. Study methodology was
      examined. Specific care aspects valued by patients were organized according to 10
      dimensions of patient-centered endometriosis care. Based on patients' assessments
      of service quality, patient-centered improvement targets and strengths were
      identified. RESULTS: Twelve of 20 eligible studies had sufficient quality to be
      included. Endometriosis patients valued all 10 dimensions of patient-centered
      endometriosis care. Problematic service quality was reported for all dimensions
      but 'coordination and integration' and 'involvement of significant others'. Two
      patient-centered strengths and 29 patient-centered improvement targets were
      identified. The most frequently reported improvement targets on which studies
      agreed were 'timely diagnosis' and 'being believed and respected by staff'.
      CONCLUSION: Endometriosis patients value patient-centeredness in addition to
      effectiveness and safety of care, and its 10 dimensions require attention in
      clinical practice. Research into the assessment and improvement of patient
      centered endometriosis care is required.

PMID- 24863285
TI  - Understanding cancer center advertisements.

PMID- 24863286
TI  - Intraoperative assessment of margins in breast conservative surgery--still in
      use?
AB  - A positive margin in breast conserving surgery is associated with an increased
      risk of local recurrence. Failure to achieve clear margins results in re-excision
      procedures. Methods for intraoperative assessment of margins have been developed,
      such as frozen section analysis, touch preparation cytology, near-infrared
      fluorescence optical imaging, x-ray diffraction technology, high-frequency
      ultrasound, micro-CT, and radiofrequency spectroscopy. In this article, options
      that might become the method of choice in the future are discussed.

PMID- 24863287
TI  - Effects of age and expertise on tactile learning in humans.
AB  - Repetitive tactile stimulation is a well-established tool for inducing
      somatosensory cortical plasticity and changes in tactile perception. Previous
      studies have suggested that baseline performance determines the amount of
      stimulation-induced learning differently in specific populations. Older adults
      with lower baseline performance than young adults, but also experts, with higher
      baseline performance than non-experts of the same age, have been found to profit
      most from such interventions. This begs the question of how age-related and
      expertise-related differences in tactile learning are reflected in
      neurophysiological correlates. In two experiments, we investigated how tactile
      learning depends on age (experiment 1) and expertise (experiment 2). We assessed
      tactile spatial and temporal discrimination accuracy and event-related potentials
      (ERPs) in 57 persons of different age and expertise groups before and after a 30
      min tactile stimulation intervention. The intervention increased accuracy in
      temporal (found in experiment 1) and spatial (found in experiment 2)
      discrimination. Experts improved more than non-experts in spatial discrimination.
      Lower baseline performance was associated with higher learning gain in experts
      and non-experts. After the intervention, P300 latencies were reduced in young
      adults and amplitudes were increased in late middle-aged adults in the temporal
      discrimination task. Experts showed a steeper P300 parietal-to-frontal gradient
      after the stimulation. We demonstrated that tactile stimulation partially
      reverses the age-related decline in late middle-aged adults and increases
      processing speed in young adults. We further showed that learning gain depends on
      baseline performance in both non-experts and experts. In experts, however, the
      upper limit for learning seems to be shifted to a higher level. 

PMID- 24863288
TI  - The role of chemistry and pH of solid surfaces for specific adsorption of
      biomolecules in solution--accurate computational models and experiment.
AB  - Adsorption of biomolecules and polymers to inorganic nanostructures plays a major
      role in the design of novel materials and therapeutics. The behavior of flexible
      molecules on solid surfaces at a scale of 1-1000 nm remains difficult and
      expensive to monitor using current laboratory techniques, while playing a
      critical role in energy conversion and composite materials as well as in
      understanding the origin of diseases. Approaches to implement key surface
      features and pH in molecular models of solids are explained, and distinct
      mechanisms of peptide recognition on metal nanostructures, silica and apatite
      surfaces in solution are described as illustrative examples. The influence of
      surface energies, specific surface features and protonation states on the
      structure of aqueous interfaces and selective biomolecular adsorption is found to
      be critical, comparable to the well-known influence of the charge state and pH of
      proteins and surfactants on their conformations and assembly. The representation
      of such details in molecular models according to experimental data and available
      chemical knowledge enables accurate simulations of unknown complex interfaces in
      atomic resolution in quantitative agreement with independent experimental
      measurements. In this context, the benefits of a uniform force field for all
      material classes and of a mineral surface structure database are discussed.

PMID- 24863289
TI  - In situ generation of iminodiacetic acid groups on nanoporous alumina for the
      reversible immobilization of enzymes and other biomolecules.
AB  - Nanoporous alumina membranes were silanized with aminopropylsilane and
      iminodiacetic acid (IDA) groups were generated in situ by reaction with
      iodoacetate. The membranes were mounted in standard filter holders, connected to
      a HPLC system and saturated with selected metal ions. Cu(II) allowed the capture
      of chicken muscle lactate dehydrogenase with such stability, repeatability and
      reproducibility that Michaelis-Menten kinetics could be studied. The IDA surface
      was stable for months and could be depleted and regenerated with metal ions
      multiple times without appreciable loss of capacity. The binding of lactate
      dehydrogenase influenced the backpressure to the extent that could be expected
      for a monolayer according to Poiseuilles law. 

PMID- 24863290
TI  - Increased fatty acid unsaturation and production of arachidonic acid by
      homologous over-expression of the mitochondrial malic enzyme in Mortierella
      alpina.
AB  - Malic enzyme (ME) catalyses the oxidative decarboxylation of L-malate to pyruvate
      and provides NADPH for intracellular metabolism, such as fatty acid synthesis.
      Here, the mitochondrial ME (mME) gene from Mortierella alpina was homologously
      over-expressed. Compared with controls, fungal arachidonic acid (ARA; 20:4 n-6)
      content increased by 60 % without affecting the total fatty acid content. Our
      results suggest that enhancing mME activity may be an effective mean to increase
      industrial production of ARA in M. alpina. 

PMID- 24863291
TI  - Highly sensitive electrochemiluminescence biosensors for cholesterol detection
      based on mesoporous magnetic core-shell microspheres.
AB  - A sensitive electrochemiluminescence (ECL) biosensor for cholesterol detection
      based on multifunctional core-shell structured microspheres (Fe3O4@SiO2
      Au@mpSiO2) is reported. This microsphere consisted of a core of silica-coated
      magnetite nanoparticle, an active transition layer of gold nanoparticles and a
      mesoporous silica shell. Scanning electron microscopy was employed to observe the
      morphology of the nanomaterials and transmission electron microscopy was used to
      further confirm the subtle structure of Fe3O4@SiO2-Au@mpSiO2. The microspheres
      possessed a large surface area that increased enzyme loading, and an active
      transition layer gold nanoparticles enhanced the ECL signal. They were used to
      immobilize cholesterol oxidase for cholesterol detection with a high sensitivity,
      low detection limit and wide linear range. The linear range was from 0.83 to 2.62
      mM with a detection limit of 0.28 uM (S/N = 3). Moreover, the reproducibility,
      stability and selectivity of the biosensor were established. 

PMID- 24863292
TI  - Non-toxic and efficient DNA extractions for soybean leaf and seed chips for high
      throughput and large-scale genotyping.
AB  - In applied soybean (Glycine max L.) breeding programs, marker-assisted selection
      has become a necessity to select value-added quantitative trait loci. The goal of
      this work was to improve marker-assisted selection workflow by developing a
      reliable, inexpensive, high-throughput DNA extraction protocol for soybean seed
      and leaf samples that does not generate hazardous waste. The DNA extraction
      protocol developed allows for the leverage of robust SNP genotyping platforms
      such as the Simple Probe Assay and KASPar v4.0 SNP Genotyping System to genotype
      thousands of seeds or leaves non-destructively in a single day with a 95 %
      success rate. This methodology makes it possible to run up to 150 SNP markers on
      the DNA extracted from a single seed chip or leaf sample. 

PMID- 24863293
TI  - Identification of soybean MYC2-like transcription factors and overexpression of
      GmMYC1 could stimulate defense mechanism against common cutworm in transgenic
      tobacco.
AB  - MYC2 is a basic helix-loop-helix Leu zipper transcription factor (TF). Here, 22
      putative soybean MYC-like TFs were identified bioinformatically. Of these TFs,
      seven MYC2-like genes without introns were isolated and characterized. All seven
      GmMYCs displayed transactivation activity in yeast cells. Six genes (excepting
      GmMYC3) were expressed in the roots, stems, leaves, flowers, and seed wall but
      not in the developing seeds and up-regulated after insect feeding. The GmMYC1
      transgenic tobacco rejected common cutworm (CCW, Spodoptera litura Fabricius)
      more strongly and lost less leaf area than the control (2.94 +/- 2.36 vs 7.84 +/-
      4.63 cm(2)). The average relative growth rate of CCW feeding on transgenic
      tobacco leaves was lower than on control tobacco leaves (136 +/- 60 vs 271 +/- 76
      %). These results indicated that GmMYC could stimulate the defense mechanism
      against insects in plants. 

PMID- 24863294
TI  - Coexpression of multiple genes reconstitutes two pathways of very long-chain
      polyunsaturated fatty acid biosynthesis in Pichia pastoris.
AB  - The introduction of novel traits to cells often requires the stable coexpression
      of multiple genes within the same cell. Herein, we report that C22 very long
      chain polyunsaturated fatty acids (VLC-PUFAs) were synthesized from C18
      precursors by reactions catalyzed by delta 6-desaturase, an ELOVL5 involved in
      VLC-PUFA elongation, and delta 5-desaturase. The coexpression of McD6DES,
      AsELOVL5, and PtD5DES encoding the corresponding enzymes, produced
      docosatetraenoic acid (C22:4 n-6) and docosapentaenoic acid (C22:5 n-3), as well
      as arachidonic acid (C20:4 n-6) and eicosapentaenoic acid (C20:5 n-3) in the
      methylotrophic yeast Pichia pastoris. The expression of each gene increased
      within 24 h, with high transcript levels after induction with 0.5 or 1 %
      methanol. High levels of the newly expressed VLC-PUFAs occurred after 144 h. This
      expression system exemplifies the recent progress and future possibilities of the
      metabolic engineering of VLC-PUFAs in oilseed crops. 

PMID- 24863295
TI  - Chimeric promoter mediates guard cell-specific gene expression in tobacco under
      water deficit.
AB  - The engineering of stomatal activity under water deficit through guard cell
      specific gene regulation is an effective approach to improve drought tolerance of
      crops but it requires an appropriate promoter(s) inducible by water deficit in
      guard cells. We report that a chimeric promoter can induce guard cell-specific
      gene expression under water deficit. A chimeric promoter, p4xKST82-rd29B, was
      constructed using a tetramer of the 82 bp guard cell-specific regulatory region
      of potato KST1 promoter (4xKST82) and Arabidopsis dehydration-responsive rd29B
      promoter. Transgenic tobacco plants carrying p4xKST82-rd29B:mGFP-GUS exhibited
      GUS expression in response to water deficit. GUS enzyme activity of p4xKST82
      rd29B:mGFP-GUS transgenic plants increased ~300 % by polyethylene glycol
      treatment compared to that of control plant but not by abscisic acid (ABA),
      indicating that the p4xKST82-rd29B chimeric promoter can be used to induce the
      guard cell-specific expression of genes of interest in response to water deficit
      in an ABA-independent manner. 

PMID- 24863296
TI  - Structural basis for RKIP binding with its substrate Raf1 kinase.
AB  - Raf1 kinase inhibitor protein (RKIP) negatively regulates the Raf1/MEK/ERK
      pathway which is vital for cell growth and differentiation. It is also a
      biomarker in clinical cancer diagnosis. RKIP binds to the N-terminus of Raf1
      kinase but little is known about the structural basis of RKIP binding with Raf1.
      Here, we demonstrate that the N-terminus of human Raf1 kinase (hRaf11-147aa)
      binds with human RKIP (hRKIP) at its ligand-binding pocket, loop "127-149", and
      the C-terminal helix by NMR experiments. D70, D72, E83, Y120, and Y181 were
      further verified as the key residues participating in the interaction of hRKIP
      and hRaf11-147aa. G143-R146 fragment was also critical for hRKIP binding with
      hRaf11-147aa, for its deletion decreased the binding affinity around 300 times,
      from 154 to 0.46 mM(-1). Our results provide important structural clues for
      designing the lead compound that disrupts RKIP-Raf1 interaction. 

PMID- 24863297
TI  - Topological state transport in topological insulators under the influence of
      hexagonal warping and exchange coupling to in-plane magnetizations.
AB  - A hexagonal warping term has been proposed recently to explain the experimentally
      observed 2D equal energy contours of the surface states of the topological
      insulator Bi2Te3. Differing from the Dirac fermion Hamiltonian, the hexagonal
      warping term leads to the opening up of a band gap by an in-plane magnetization.
      We study the transmission between two Bi2Te3 segments subjected to different in
      plane magnetizations and potentials. The opening up of a bandgap, and the
      accompanying displacement and distortion of the constant energy surfaces from
      their usual circular shapes by the in-plane magnetizations, modify the transverse
      momentum overlap between the two Bi2Te3 segments, and strongly modulate the
      transmission profile. The strong dependence of the TI surface state transport of
      Bi2Te3 on the magnetization orientation of an adjacent ferromagnetic layer may
      potentially be utilized in, e.g., a memory readout application. 

PMID- 24863298
TI  - Effect of diquafosol ophthalmic solution on the optical quality of the eyes in
      patients with aqueous-deficient dry eye.
AB  - PURPOSE: To investigate the short- and long-term effects of diquafosol ophthalmic
      solution on the optical quality of the eyes in patients with aqueous-deficient
      dry eye. METHODS: Sixteen eyes in 16 patients with mild or moderate aqueous
      deficient dry eye were treated with 3% diquafosol ophthalmic solution. Ocular
      higher-order aberrations (HOAs) were measured with a wavefront sensor before and
      at 15 min after diquafosol instillation at the baseline visit and at 4 weeks
      after treatment initiation. Dry eye symptoms, tear break-up time (BUT),
      corneal/conjunctival fluorescein staining and Schirmer's test were also evaluated
      before and after treatment with diquafosol. RESULTS: Treatment with diquafosol
      ophthalmic solution significantly improved dry eye symptoms, corneal staining and
      BUT. Compared with mean total HOAs at baseline (0.180 +/- 0.06 MUm), those at 4
      weeks after treatment significantly decreased (0.148 +/- 0.039 MUm; p = 0.035),
      whereas those 15 min after diquafosol instillation at the baseline visit did not
      change significantly (0.170 +/- 0.049 MUm; p = 0.279). CONCLUSIONS: Although no
      significant change in HOAs was observed as a short-term effect of a single-drop
      instillation of diquafosol, long-term use of diquafosol to treat aqueous
      deficient dry eye reduced HOAs as well as improved corneal epithelial damage and
      tear film stability.

PMID- 24863301
TI  - Making sense of health rankings.
AB  - In an era of increasingly complex medical care and escalating costs, healthcare
      decision-makers often rely on a broad range of indicators to gauge the health of
      a population, the quality of hospital care and the performance of healthcare
      systems. Reports that rank the health of Canadians and Canada's healthcare
      systems according to these indicators are widely cited in the media. These
      reports attempt to condense a complicated array of statistics into a relatively
      simple number, a rank that is used to make international and provincial
      comparisons. These reports have often been inconsistent. Unlike a familiar
      economic indicator - the gross domestic product (GDP), which represents a complex
      entity with a single number calculated according to an internationally agreed
      upon methodology - rankings of health and healthcare are not yet standardized or
      well understood. This article aims to improve readers' understanding of ranking
      reports. It outlines the components and processes that underlie health rankings
      and explores why such rankings can be difficult to interpret. 

PMID- 24863299
TI  - Precipitation and winter temperature predict long-term range-scale abundance
      changes in Western North American birds.
AB  - Predicting biodiversity responses to climate change remains a difficult
      challenge, especially in climatically complex regions where precipitation is a
      limiting factor. Though statistical climatic envelope models are frequently used
      to project future scenarios for species distributions under climate change, these
      models are rarely tested using empirical data. We used long-term data on bird
      distributions and abundance covering five states in the western US and in the
      Canadian province of British Columbia to test the capacity of statistical models
      to predict temporal changes in bird populations over a 32-year period. Using
      boosted regression trees, we built presence-absence and abundance models that
      related the presence and abundance of 132 bird species to spatial variation in
      climatic conditions. Presence/absence models built using 1970-1974 data forecast
      the distributions of the majority of species in the later time period, 1998-2002
      (mean AUC = 0.79 +/- 0.01). Hindcast models performed equivalently (mean AUC =
      0.82 +/- 0.01). Correlations between observed and predicted abundances were also
      statistically significant for most species (forecast mean Spearman's rho = 0.34
      +/- 0.02, hindcast = 0.39 +/- 0.02). The most stringent test is to test predicted
      changes in geographic patterns through time. Observed changes in abundance
      patterns were significantly positively correlated with those predicted for 59% of
      species (mean Spearman's rho = 0.28 +/- 0.02, across all species). Three
      precipitation variables (for the wettest month, breeding season, and driest
      month) and minimum temperature of the coldest month were the most important
      predictors of bird distributions and abundances in this region, and hence of
      abundance changes through time. Our results suggest that models describing
      associations between climatic variables and abundance patterns can predict
      changes through time for some species, and that changes in precipitation and
      winter temperature appear to have already driven shifts in the geographic
      patterns of abundance of bird populations in western North America. 

PMID- 24863302
TI  - The burden of unhealthy living in Ontario: the impact of smoking, alcohol, diet,
      physical inactivity and stress on life expectancy.

PMID- 24863303
TI  - In conversation with Chris Power.

PMID- 24863304
TI  - Enhancing quality and safety standards for older people in Canadian hospitals: a
      national collaboration.
AB  - In this article, the authors present quality and safety standards for older
      people in hospital, derived from a national dialogue involving inter-professional
      experts, key stakeholders and opinion leaders. They report the consensus process
      and present the standard statements with corresponding operational definitions,
      along with relevant clinical topics. This work can serve as a platform for
      service planners, evaluators and policy makers who are endeavouring to ensure
      that older people receive quality care and service when admitted to a Canadian
      hospital. 

PMID- 24863305
TI  - Partnership and measurement: the promise, practice and theory of a successful
      health social networking strategy.
AB  - Patient health management (PHM) was launched as a promising paradigm to close
      care gaps, the inequities between usual and best care, for whole patient
      populations. PHM's core premise was that interventions of multidisciplinary,
      community-oriented partnerships that used repeated measurement and feedback of
      provider practices, clinical and economic outcomes and general communication of
      relevant health knowledge to all stakeholders would continuously make things
      better. This article reviews the evolution of PHM from its genesis in a series of
      casual hospital-based networks to its maturation in a province-wide, community
      focused, clustered-lattice social network that facilitated the improved clinical
      and cost-efficient care and outcomes of whole patient populations. The factors
      underlying PHM's clinical and cost efficacy, specifically its patient-centric
      social networking structures and integral measurement and knowledge translation
      processes, offer continuing promise to optimally manage the care of our
      increasingly aged patient populations, with their high burden of chronic diseases
      and disproportionately large care gaps. In an era when patients are demanding and
      leading change, and governments are struggling fiscally, PHM's clinical efficacy
      and cost-efficiency are especially resonant. Things can be better. 

PMID- 24863306
TI  - Developing an institute of medicine-aligned framework for categorizing primary
      care indicators for quality assessment.
AB  - The Institute of Medicine (IOM) framework has been used frequently to assess and
      monitor quality in secondary and tertiary care, but not in primary care. This
      article describes and proposes a conceptual framework for categorizing primary
      care indicators that align with the IOM's six aims for quality in healthcare
      performance (Safe, Effective, Patient-Centred, Timely, Efficient and Equitable.)
      Using an iterative process, the authors developed and compared a primary care
      framework for categorizing indicators in the Quality in Family Practice Book of
      Tools (QBT) with the IOM aims and other local healthcare systems frameworks
      (Integrated and Continuous, Appropriate Practice Resources). They also compared,
      cross-matched and analyzed their QBT categories and indicators with other
      international primary care assessment tools. And they compared the QBT titles and
      descriptions of groups of indicators with those published in the international
      tools. 

PMID- 24863309
TI  - Social media in healthcare: it's so five years ago?

PMID- 24863307
TI  - Facilitating specialist to primary care transfer with tools for transition: a
      quality of care improvement initiative for patients with type 2 diabetes.
AB  - The epidemic of diabetes has increased pressure on the whole spectrum of the
      healthcare system including specialist centres. The authors' own specialist
      centre at The Ottawa Hospital has 20,000 annual visits for diabetes, 80% of which
      are follow-up visits. Since it is a tertiary facility, managers, administrators
      and clinicians would like to increase their ability to see newly referred
      patients and decrease the number of follow-up visits. In order to discharge
      appropriate diabetes patients, the authors decided it was essential to strengthen
      the transition process to decrease both the pressure on the centre and the risk
      for discontinuity of diabetes care after discharge. 

PMID- 24863308
TI  - Integrated care, information management and information technology in Canada:
      have we made any progress in the past 12 years?
AB  - A dozen years ago, a seminal article was written by Leatt, Pink and Guerriere
      that boldly stated that Canada did not have integrated healthcare but, rather, a
      hodgepodge of disconnected parts! The article also stated categorically that
      Canadian regional health authorities could not provide comprehensive integrated
      care since they were not responsible for drugs dispensed from retail pharmacies
      or for medical care provided by physicians. Twelve years later, some progress
      toward integrated care has been made, though many would argue that it is both
      inadequate and disappointing - even if Canada's provincial health systems would
      like to integrate services across an ever-expanding continuum of care to better
      serve patients. 

PMID- 24863310
TI  - Leadership, a central ingredient for a successful quality agenda: a qualitative
      study of Canadian leaders' perspectives.
AB  - Quality and safety (QS) teams have emerged as one strategy to improve the quality
      of care and safety. This article aims to enhance understanding of, and identify
      implications for, leaders in implementing successful QS teams. Research findings
      from the authors' study that explored barriers and facilitators of Canadian QS
      teams highlight the need for delineated leadership and accountability, focused
      strategic plans, available data, dedicated resources and targeted messaging to
      engage staff and physicians. While top-down leadership strategies were
      predominantly reported, developing leaders at all organizational levels was
      acknowledged as key to sustaining a quality culture and advancing the quality
      agenda. 

PMID- 24863311
TI  - Occupational therapy: cost-effective solutions for changing health system needs.
AB  - Evidence shows occupational therapy interventions are cost-effective in treating
      or preventing injury and improving health outcomes in areas such as falls
      prevention, musculoskeletal injury, stroke rehabilitation, early intervention in
      developmental disabilities, respiratory rehabilitation and home care. Additional
      research indicates opportunities for occupational therapy to play an increased
      role in the management of health outcomes in complex and chronic diseases, pain
      management, non-pharmaceutical mental health interventions, dementia, end-of-life
      or palliative care and home care. This article aligns the discussion of health
      system transformation with literature identifying the cost-effectiveness of
      occupational therapy in Canada. 

PMID- 24863312
TI  - Comparative models of cervical cancer screening in Manitoba.
AB  - The laboratory system in Manitoba for routine cervical screening is outdated and
      costly. We developed a costing framework for the implementation of new cervical
      cancer screening technology models. The direct healthcare costs in the baseline
      model, the conventional Papanicolaou smear test, were compared with estimates of
      two newer technology platforms, liquid-based cytology and human papillomavirus
      (HPV) testing. The findings revealed that HPV testing as a primary screening
      model for women aged 30 years and older represented the least-cost strategy.
      Liquid-based cytology would be used for routine screening of women under 30 years
      of age and to triage women 30 years and older whose results were HPV positive. 

PMID- 24863313
TI  - Avoiding "culture rejection" in healthcare mergers and acquisitions: how New
      Heights Community Health Centres and York Community Services minimized the
      culture risk when forming Unison Health and Community Services.
AB  - Among the requirements for a successful merger or acquisition are strategic
      rationale, rigorous due diligence, the right price and revenue and cost
      synergies. However, bridging the culture gap between organizations is frequently
      overlooked. The leaders of New Heights Community Health Centres and York
      Community Services explicitly considered culture in their merger to form Unison
      Health and Community Services, and they used employee engagement surveys to
      assess culture in their merger planning and post-merger integration. How Unison
      Health leaders avoided the risk of culture rejection to achieve a successful
      merger, and the lessons learned from their experience, is the focus of this
      article. 

PMID- 24863314
TI  - Can this care be provided at home?

PMID- 24863315
TI  - Exogenous normal lymph alleviates lipopolysaccharide-induced acute lung injury
      through lessening the adhesion molecules.
AB  - PURPOSE: To evaluate the role of exogenous normal lymph (ENL) on
      lipopolysaccharide (LPS)-induced acute lung injury (ALI) in rats. METHODS: ALI
      was induced by the jugular vein injection of LPS (iv, 15 mg/kg) in rats of the
      LPS and LPS+ENL groups within 15 min, then, ENL without cell components (5 ml/kg)
      was infused at the speed of 0.5 ml per minute in the LPS+ENL group, the same
      amount of saline was administered in the LPS group. The rats in the sham group
      received the same surgical procedure and saline. The histomorphology and the
      levels of P-selectin, intercellular adhesion molecule-1 (ICAM-1), myeloperoxidase
      (MPO) in pulmonary tissue were assessed. RESULTS: LPS induced pulmonary injury as
      well as increased the wet/dry weight ratio (W/D) and the levels of P-selectin,
      ICAM-1, and MPO in pulmonary tissues. These deleterious effects of LPS were
      significantly ameliorated by ENL treatment. CONCLUSION: Exogenous normal lymph
      could markedly alleviate the acute lung injury induced by lipopolysaccharide, and
      its effects might be related to lessening the adhesion molecules.

PMID- 24863316
TI  - Effects of human chorionic gonadotropin on the normal testicular tissue of rats.
AB  - PURPOSE: To investigate the effects of human chorionic gonadotropin (hCG) on the
      testicular tissue of young male rats. METHODS: Male Wistar rats were assigned to
      groups (10 rats/group).Control Group received subcutaneous saline solution; Group
      1 received hCG 50 UI/Kg/dose; and Group 2 received hCG 100 UI/Kg/dose, daily for
      15 days. Half was submitted to bilateral orchiectomy on the 16th day and the
      other half 45 days after the beginning of the hormone application. Testicles were
      weighed, measured and has their volumes determined. The diameter of the tubules
      and the thickness of the seminiferous epithelium were measured. RESULTS: Control
      Group presented the highest values of testicles volume and weight. Rats in the
      Control presented normal histology. In G1 and G2 atrophy of the seminiferous
      tubules, apoptosis of germ cells and multinucleated giant cells were observed.
      Comparing groups, in the first operation Control rats had higher diameter values.
      In the second operation, the Control was only different from G1. As for
      thickness, Control had higher values in both operations. Comparing the time of
      operation, the diameter values were higher in G1 and G2 in the second operation.
      For all groups, the thickness of the epithelium was higher in the second
      operation. CONCLUSIONS: Human chorionic gonadotropin is gonadotoxic in rats. This
      effect was temporary and can affect reproductive potential. The total recovery of
      testicular damage in the studied range could not be proved, and the effects were
      not dose-dependent.

PMID- 24863317
TI  - Histological study of rat ovaries cryopreserved by vitrification or slow freezing
      and reimplanted in the early or late postmenopausal stage.
AB  - PURPOSE: To compare two rat ovary cryopreservation techniques (vitrification vs.
      slow freezing) and two postmenopausal stages (early vs. late) with regard to
      graft take. METHODS: Thirty-three Wistar rats were submitted to bilateral
      oophorectomy. One ovary was submitted to histological analysis while the other
      was cryopreserved by slow freezing or vitrification. The cryopreserved ovary was
      thawed and reimplanted in the greater omentum one week (early menopause) or one
      month (late menopause) after oophorectomy. One month after ovary reimplantation,
      the graft take was evaluated macroscopically and histologically. RESULTS: Six of
      the animals were used ascontrols and seven died. The histological findings of 20
      animals included atretic follicles (n=4), primordial follicles (n=2), and corpus
      luteum with primordial follicles (n=3). No ovarian tissue was found in 11
      animals. Vitrification resulted in a higher graft take rate than slow freezing
      (50% vs. 38.5%), but the difference was not statistically significant. However,
      the graft take rate was 9.3 times higher in the early than in the late
      postmenopausal stage (61.5% vs. 14.3%) (p=0.043). CONCLUSION: Vitrification was
      superior to slow freezing as ovarian cryopreservation technique, and grafting was
      significantly more successful when the ovary was reimplanted in the late
      postmenopausal stage.

PMID- 24863318
TI  - Hematology of Swiss mice (Mus musculus) of both genders and different ages.
AB  - PURPOSE: To describe the hematologic values of male and female, young and adult,
      Swiss mice (Mus musculus). METHODS: Mus musculus (n=14) were randomly selected
      and separated by gender. The male and female, young and adult animals were
      sedation to obtain a blood sample, by intracardiac route at 30, 45, 60, 75, 90,
      105 and 120 days after birth. RESULTS: The Swiss mouse hemogram values obtained,
      in relation to total eosinophils, basophils, and number of platelets, there was
      no statistical differences according to the genders or the age of the animals.
      Regarding the erythrocyte, hemoglobin and hematocrit values obtained, these were
      higher in females. The RDW-CD and MPV values were higher in the females than in
      the males. CONCLUSIONS: Lymphocytes are the predominant cells in the peripheral
      blood. The collection of 800 uL of blood by intracardiac route, every 15 days,
      did not affect the health of the animals. Analyses of the blood samples
      contribute to the experimental models provided by the Central Animal Facility of
      UFMS and used by professors.

PMID- 24863319
TI  - An experimental model of chronic rhinosinusitis in rabbits without bacterial
      inoculation.
AB  - PURPOSE: Evaluate and compare two different experimental techniques of maxillary
      sinus ostium occlusion using N-butyl cyanoacrylate in developing chronic
      histological findings without the inoculation of pathogenic bacteria among
      rabbits. METHODS: In a randomized study, sixteen New Zealand rabbits were
      assigned for occlusion of the right maxillary sinus through a transmaxillary
      approach or through the roof of the nasal cavity. The contralateral sinus served
      as a control. After 12 weeks, the animals were sacrificed for blinded
      histopathological analysis of the maxillary sinus mucosa. RESULTS:
      Histopathological changes consistent with CRS were found in eight (100%) of the
      maxillary sinuses approached transmaxillary and three of those through the roof
      of the nasal cavity (37.5%), p 0.008 and 0.250, respectively, comparing with the
      control side. Chronic mucosal changes were significantly better induced using the
      transmaxillary approach (p 0.026). CONCLUSION: It is possible to induce a model
      of chronic sinusitis among rabbits with transmaxillary sinus occlusion without
      bacterial inoculation. This model can be replicated for future cellular studies.

PMID- 24863320
TI  - Early postoperative changes in hematological, erythrocyte aggregation and blood
      coagulation parameters after unilateral implantation of polytetrafluoroethylene
      vascular graft in the femoral artery of beagle dogs.
AB  - PURPOSE: The failure of small-caliber vascular grafts still means a serious
      problem. Concerning the early postoperative complications we aimed to investigate
      the hemostaseological and hemorheological aspects of this issue in a canine
      model. METHODS: In the Control group only anesthesia was induced. In the Grafted
      group under general anesthesia a 3.5-cm segment was resected unilaterally from
      the femoral artery and replaced with a PTFE graft (diameter: 3 mm). On the 1st
      3rd-5th-7th and 14th postoperative days the skin temperature of both hind limbs
      was measured, and blood sampling occurred for hematological, hemostaseological
      and hemorheological tests. RESULTS: The skin temperature of the operated versus
      intact limbs did not differ. In the Grafted group leukocyte count was elevated by
      the 1st postoperative day, while platelet count increased over the entire follow
      up period. Fibrinogen concentration rose on the 1st-5th days, activated partial
      thromboplastin time increased on the 3rd-7th days. Erythrocyte aggregation was
      enhanced significantly on the 1st-5th days. In specimens taken on the 14th day,
      histologically we found matured thrombus narrowing the graft lumen. CONCLUSIONS:
      Small-caliber PTFE graft implantation into the femoral artery caused significant
      changes in several hemostaseological and hemorheological parameters. However,
      better clarifying the factors leading to early thrombosis of these grafts needs
      further studies.

PMID- 24863321
TI  - Diclofenac topical gel in excisional wounds maintain heal quality and reduce
      phlogistic signals.
AB  - PURPOSE: To investigate diclofenac topical gel as an alternative to reduce
      phlogistic signals and maintain quality of wound repair. METHODS: Fifteen Wistar
      rats were used in this study; four excisional wounds were performed on the dorsum
      of each animal. Once in a day, cranial wounds received topical diclofenac gel
      administration and caudal wounds were washed with isotonic saline. After seven,
      14 and 21 postoperative days, five animals were randomly chosen for macroscopic
      and microscopic wound analysis. RESULTS: On the 7th day: diclofenac wounds showed
      significant higher scab formation, however showed less phlogistic signal;
      diclofenac wounds had larger area and had less neutrophil invasion. On the 14th
      day: No area difference was noted and diclofenac wounds showed less hyperemia and
      phlogistic signals; diclofenac wounds showed greater keratinocytes invasion. On
      the 21st day: Almost all wounds were closed and there were no difference
      regarding the type of scar formation; diclofenac wounds showed greater monocytes
      invasion and lower angiogenesis level. No difference was noted in any
      postoperative day regarding fibroblast invasion, collagen deposit quantity and
      quality. CONCLUSION: Diclofenac topical gel is capable of reducing phlogistic
      signals and do not cause fibroblast or keratinocyte downregulation thus do not
      lead to excisional wound healing impairment.

PMID- 24863322
TI  - Amniotic membrane as a biological dressing in infected wound healing in rabbits.
AB  - PURPOSE: To investigate amniotic membrane as a biological dressing in infected
      wound healing in rabbits. METHODS: The use of preserved amniotic membranes (AMs)
      was examined using 15 rabbits with experimentally induced wound infections on
      their backs. Healing was histologically evaluated during different phases
      including inflammation, granulation, epithelialization, and fibroplasia. The
      animals were distributed into three groups for histological study at seven, 14,
      21, and 28 days post-wound induction. Group A did not receive treatment: the
      wound was left exposed and dry; Group B received a daily exposure treatment with
      collagenase; and Group C received one AM, which also remained exposed. RESULTS: A
      marked reduction of the inflammatory phase was observed in Group C at 21 days,
      and the granulation phase of this healing increased at 14 days. Epithelialization
      was similar among the three groups, and fibroplasia was more pronounced in Group
      C at 14 days. Furthermore, gradual collagen organization also began for the
      animals in Group B at 14 days. CONCLUSION: The amniotic membrane did not
      significantly alter the inflammation, epithelialization, or fibroplasia phases
      but did increase angiogenesis up to Day 14 compared with the dry dressing and
      collagenase treatments.

PMID- 24863323
TI  - C-reactive protein and vasospasm after aneurysmal subarachnoid hemorrhage.
AB  - PURPOSE: To evaluate the relationship between C reactive protein levels and
      clinical and radiological parameters with delayed ischemic neurological deficits
      and outcome after aneurysmal subarachnoid hemorrhage. METHODS: One hundred adult
      patients with aneurismal SAH were prospectively evaluated. Besides the baseline
      characteristics, daily C-reactive protein levels were prospectively measured
      until day 10 after subarachnoid hemorrhage. The primary end point was outcome
      assessed by Glasgow Outcome Scale, the secondary was the occurrence of delayed
      ischemic neurological deficits (DINDs). RESULTS: A progressive increase in the
      CRP levels from the admission to 3rd postictal day was observed, followed by a
      slow decrease until the 9th day. Hemodynamic changes in TCD were associated with
      higher serum CRP levels. Patients with lower GCS scores presented with increased
      CRP levels. Patients with higher Hunt and Hess grades on admission developed
      significantly higher CRP serum levels. Patients with higher admission Fisher
      grades showed increased levels of CRP. A statistically significant inverse
      correlation was established in our series between CRP serum levels and GOS on
      discharge and CRP levels. CONCLUSIONS: Higher C-reactive protein serum levels are
      associated with worse clinical outcome and the occurrence of delayed ischemic
      neurological deficits. Because C-reactive protein levels were significantly
      elevated in the early phase, they might be a useful parameter to monitor.

PMID- 24863324
TI  - A meta-analysis of the efficacy of ureteroscopic lithotripsy and extracorporeal
      shock wave lithotripsy on ureteral calculi.
AB  - PURPOSE: To re-evaluated the clinic efficacy of ureteroscopic lithotripsy (URS)
      and extracorporeal shock wave lithotripsy (ESWL) on ureteral calculi with
      Cochrane systematic reviews in this paper. METHODS: We searched clinical
      randomized controlled trials and prospective controlled trials in databases such
      as Cochrane library, Medline, Springer, Elsevier Science Direct, PubMed. Pooled
      estimate of risk ratios (RRs), standard mean difference (SMD) with 95% confidence
      intervals (CIs) were used as measure of effect sizes. Summary effect estimates
      were also stratified by sample size, study design and study region. The overall
      effect sizes were derived using a random-effects model or fixed-effects model
      when appreciated, and meta-analysis were conducted with software RewMan 5.0.
      RESULTS: The meta-analysis suggested that there were significant differences of
      post-treatment stone free rate, repeat treatment rate, patients' satisfaction,
      incidence of postoperative complications, operation time and hospital stays
      between ESWL treatment cases and URS treatment cases. But in the sample sizes
      analysis, there were no significant differences of the post-treatment stone free
      rate and repeat treatment rate when the sample sizes were less than 100.
      CONCLUSIONS: Compared to the ureteroscopic lithotripsy treatment, extracorporeal
      shock wave lithotripsy treatment provided a significantly lower post-treatment
      stone free rate, but it also obviously brought out less postoperative
      complications, shorter operation time and hospital stays.

PMID- 24863326
TI  - [Medical students: Informed consent discussions].

PMID- 24863325
TI  - Health economic impact of high-dose versus standard-dose cytarabine induction
      chemotherapy for acute myeloid leukaemia.
AB  - BACKGROUND: Induction chemotherapy for acute myeloid leukaemia (AML) is one of
      the most resource-intensive cancer therapies delivered in hospitals. AIMS: To
      assess the health resource impact of different chemotherapy approaches for AML
      commonly used in Australia. METHODS: A retrospective analysis was undertaken in
      63 patients aged 18-55 years with AML given induction with either 7 + 3
      (cytarabine 100 mg/m(2) days 1-7 and idarubicin 12 mg/m(2) days 1-3) or HiDAC-3
      (high-dose cytarabine 3 g/m(2) twice daily days 1, 3, 5 and 7 and idarubicin 12
      mg/m(2) days 1-3) chemotherapy. Average costs of hospitalisation, pathology,
      radiology, chemotherapy and ancillary drugs were calculated and compared with
      current Victorian casemix funding. Two consolidation approaches, HiDAC
      (cytarabine 3 g/m(2) twice daily days 1, 3, 5 and 7) * either three or four
      cycles (following 7 + 3) and IcE (idarubicin 12,mg/m(2) days 1-2, cytarabine 100
      mg/m(2) * 5 days and etoposide 75 mg/m(2) * 5 days) * 2 cycles (following HiDAC
      3) were modelled, using a policy of discharge following completion of
      chemotherapy with outpatient monitoring. RESULTS: The cost (in AUD) of induction
      was similar between 7 + 3 ($58,037) and HiDAC-3 ($56,902), with bed day costs
      accounting for 61-62% of the total expense. Blood bank costs ranked second,
      accounting for 15%. Accumulated costs for HiDAC consolidation were $44,289 for a
      three-cycle protocol and $59,052 for four cycles ($14,763 per cycle) versus
      $31,456 for two cycles of IcE consolidation ($15,728 per cycle). Overall, the
      classical 7 + 3 -> HiDAC approach ($102,326/$117,089 for three or four
      consolidation cycles) incurs a greater cost than a HiDAC-3 -> IcE * 2 approach
      ($88,358). For patients requiring complete hospitalisation until neutrophil
      recovery, the estimated costs of treatment will be even higher, ranging between
      $122,282 for HiDAC-3 -> IcE * 2, $153,212 for 7 + 3 -> HiDAC * 3 and $184,937 for
      7 + 3 -> HiDAC * 4. State-based casemix funding for non-complicated AML therapy
      is currently $74,013 for 7 + 3 -> HiDAC * 4, $64,177 for 7 + 3 -> HiDAC * 3 and
      $54,340 for HiDAC-3 -> IcE * 2 based on outpatient recovery after consolidation
      chemotherapy. These calculations do not take into account additional resource
      implications associated with complications of consolidation chemotherapy or
      reinduction for treatment failure. CONCLUSION: Regimens minimising the total
      number of chemotherapy cycles may represent the most efficient use of limited
      health resources for the treatment of AML.

PMID- 24863328
TI  - [The obese patient in the intensive care unit--what is different?].
AB  - In many countries over the past years there has been a marked increase in the
      number of people with severe overweight - especially among the younger age groups
      up to 35 years. Accordingly, the number of intensive care patients suffering
      additionally from a significant obesity is also increasing continuously. Some
      particular features of these patients need to be observed. Differences to normal
      weight patients involve, for example, respiratory physiology: the obesity leads
      to a decrease of lung volume and to a marked increase in breathing work as well
      as oxygen consumption. Clinically relevant changes occur in the upper airways and
      neck. Thus, mask ventilation, intubation or surgical interventions to secure the
      airways are clearly more difficult than in normal-weight patients. Obese
      intensive care patients are therefore primarily to be considered as patients with
      difficult airway conditions. In addition in cases of extreme obesity, drug
      distribution, degradation and excretion can differ from those of normal-weight
      patients. This must be taken into account for medication dosing. In spite of the
      overweight, obese patients may be undernourished upon admission to the ICU. Thus,
      for this group of patients also, enteral nutrition should be started as early as
      possible. Although obesity is accompanied by a higher mortality on account of the
      many possible comorbidities, numerous studies have confirmed that even extreme
      obesity does not increase the mortality rate in comparison with that of normal
      weight patients.

PMID- 24863330
TI  - [Readers ask - experts respond - mechanical autotransfusion].

PMID- 24863329
TI  - [Invasive emergency techniques--decompression of the pleura].
AB  - On-scene invasive emergency procedures, such as cricothyroidotomy, chest drain,
      intraosseous puncture or even on-field-amputation, are often unavoidable, when
      indicated, and present a major challenge for the emergency physician. Personal,
      temporal or local conditions are often unsuitable. Even with regular intervention
      by the emergency medical service, "last resort" measures occur very infrequently,
      particularly in relation to paediatric emergencies. Beside a theoretical
      education, practice-oriented course concepts are necessary to achieve a high
      quality of these measures. This article presents the use of decompression of the
      pleura on adults and children, with reference to indication, implementation,
      problems and risks. It is the second part of a series of four articles on the
      subject of invasive emergency techniques.

PMID- 24863331
TI  - [Preventive vaccinations for medical personnel].
AB  - Vaccinations are among the most efficient and important preventive medical
      procedures. Modern vaccines are well tolerated. In Germany there are no longer
      laws for mandatory vaccinations, either for the general public or for medical
      personnel. Vaccinations are now merely "officially recommended" by the top health
      authorities on the basis of recommendations from the Standing Committee on
      Vaccinations (STIKO) of the Robert Koch Institute (RKI) according to S 20 para 3
      of the Protection against Infection law (IfSG). The management of vaccine damage
      due to officially recommended vaccinations is guaranteed by the Federal States.
      Whereas vaccinations in childhood are generally considered to be a matter of
      course, the willingness to accept them decreases markedly with increasing age. In
      the medical sector vaccinations against, for example, hepatitis B are well
      accepted while other vaccinations against, for example, whooping cough or
      influenza are not considered to be so important. The fact that vaccinations,
      besides offering protection for the medical personnel, may also serve to protect
      the patients entrusted to medical care from nosocomial infections is often
      ignored.

PMID- 24863332
TI  - [Drug Interactions - An underestimated problem in AINS?].

PMID- 24863333
TI  - [Anesthetic drug interactions].
AB  - Pharmaceutical, pharmacokinetic and pharmacodynamic drug-drug interactions (DDI)
      can complicate or facilitate anesthesia. Knowledge of the basic DDI mechanisms
      and DDI databases helps to avoid unwanted DDIs and to optimize wanted DDIs such
      as antidotes or desired synergism. Concerning pharmaceutical DDI
      (=incompatibilities) special attention must be paid to very acidic or basic
      drugs, polyvalent ions such as calcium and emulsions like propofol. Inducers or
      inhibitors of cytochrome p450 3A4 can complicate postoperative therapy of raised
      blood pressure or pain (pharmacokinetic DDI). Pharmacodynamik DDIs like the
      impact of many drugs on blood pressure are the day-to-day armamentarium for
      anesthetists.

PMID- 24863334
TI  - [Drug interactions in intensive care medicine].
AB  - Drug-drug interactions are a common problem in elderly multi-morbid patients
      receiving polypharmacy. A high quantity of prescribed drugs is associated with an
      increase in the risk of adverse effects and drug-drug interactions. More and more
      medical and pharmaceutical stakeholders are involved in the drug therapy of
      critically ill patients. In the future it will be important to comprehend the
      medication as a common task. The patient will get the best therapy available, if
      the cooperation is successful. In general, drug interactions may be related to
      pharmacokinetic and pharmacodynamic aspects. Pharmacokinetic drug interactions
      concern the influence of the cytochrome P450 enzymes and transport proteins in
      the body. Pharmacodynamic interactions can be found, for example, as an additive
      effect of drugs which are combined. The relevance of both aspects must
      accordingly be considered and negative impact should be avoided.

PMID- 24863335
TI  - [Drug interactions in emergency medicine].
AB  - Drug interactions in emergency medicine can occur in many forms and can result in
      different complications. Drug interactions can be the primary cause for the
      emergency call, but also they can happen after the application of different drugs
      at the scene. Emergency physicians need to be aware of possible interactions of
      their own emergency drugs. Additionally, interactions of different medications
      prescribed by physicians, non-prescription drugs and also by food are possible.
      Emergency drugs should never be mixed in a single syringe or applied together in
      a single infusion bag. Solving of medications always needs to be in accordance
      with the official instruction leaflet.

PMID- 24863338
TI  - Hydrogen sulfide ameliorates high-glucose toxicity in rat peritoneal mesothelial
      cells by attenuating oxidative stress.
AB  - BACKGROUND/AIMS: Continuous exposure of the peritoneal membrane to high-glucose
      (HG) peritoneal dialysis fluids (PDFs) can produce peritoneal mesothelial cells
      (PMCs) injury. It has been demonstrated that hydrogen sulfide (H2S), the third
      endogenous gaseous mediator identified after nitric oxide and carbon monoxide,
      exhibits a potent protective effect on cell activity. We studied the toxic
      effects of HG PDFs and their reversal by H2S on cultures of rat PMCs. METHODS:
      Synchronized confluent rat PMCs were incubated with 2.5% glucose PDFs with or
      without NaHS, an H2S donor. Cell viability was assessed by methyl thiazolyl
      tetrazolium assay and flow cytometry. The level of phospho-p38 mitogen-activated
      protein kinase (MAPK) was analyzed by immunoblotting. p53, Bax and Bcl-2 mRNA
      expressions by rat PMCs were detected by real-time PCR. The levels of reactive
      oxygen species (ROS), superoxide dismutase (SOD) activity and caspase-3 activity
      were measured. RESULTS: Exposure of rat PMCs to 2.5% glucose PDFs for 24 h
      resulted in a significant induction of apoptosis, which was attenuated by NaHS.
      NaHS also restored the 2.5% glucose PDF-induced increase in phospho-p38 MAPK
      (indices of cellular toxicity). Further investigation of the apoptotic mechanisms
      in rat PMCs demonstrated that HG activated caspase-3 and upregulated Bax, while
      it downregulated Bcl-2. All the above responses were prevented by pretreatment
      with NaHS. Moreover, NaHS reversed the 2.5% glucose PDF-induced increase in ROS
      generation and decrease in SOD activity. CONCLUSIONS: These findings suggest that
      HG PDFs significantly inhibit rat PMC viability, leading to peritoneal injury.
      H2S exhibits a potent anti-apoptotic ability by attenuating oxidative stress and
      inhibiting caspase-3 activation, which in turn restores peritoneal injury.

PMID- 24863339
TI  - NetTepi: an integrated method for the prediction of T cell epitopes.
AB  - Multiple factors determine the ability of a peptide to elicit a cytotoxic T cell
      lymphocyte response. Binding to a major histocompatibility complex class I (MHC
      I) molecule is one of the most essential factors, as no peptide can become a T
      cell epitope unless presented on the cell surface in complex with an MHC-I
      molecule. As such, peptide-MHC (pMHC) binding affinity predictors are currently
      the premier methods for T cell epitope prediction, and these prediction methods
      have been shown to have high predictive performances in multiple studies.
      However, not all MHC-I binders are T cell epitopes, and multiple studies have
      investigated what additional factors are important for determining the
      immunogenicity of a peptide. A recent study suggested that pMHC stability plays
      an important role in determining if a peptide can become a T cell epitope.
      Likewise, a T cell propensity model has been proposed for identifying MHC binding
      peptides with amino acid compositions favoring T cell receptor interactions. In
      this study, we investigate if improved accuracy for T cell epitope discovery can
      be achieved by integrating predictions for pMHC binding affinity, pMHC stability,
      and T cell propensity. We show that a weighted sum approach allows pMHC stability
      and T cell propensity predictions to enrich pMHC binding affinity predictions.
      The integrated model leads to a consistent and significant increase in predictive
      performance and we demonstrate how this can be utilized to decrease the
      experimental workload of epitope screens. The final method, NetTepi, is
      publically available at www.cbs.dtu.dk/services/NetTepi . 

PMID- 24863341
TI  - The nature of interactions in nicotinamide crystal.
AB  - In this study, we analyze the nature of intermolecular interactions in
      nicotinamide complexes appearing in conformations found in the crystal structure,
      including many-body effects. In doing so, we employ symmetry-adapted perturbation
      theory based on density functional theory description of monomers, and we perform
      the many-body variational-perturbational interaction energy decomposition. The
      principal finding of this study is that the stability of nicotinamide complexes
      is a complicated interplay of four (large in magnitude) interaction-energy
      components, i.e. induction, dispersion, electrostatic and exchange repulsion.
      However, the last two contributions cancel each other out to a large extent. In
      the case of considered three-body complexes, the nonadditivity effects are found
      to be not important. Based on the results of topological analysis of charge
      densities we characterized also the properties of short H ? H contact and
      identified it as a weak noncovalent closed shell interaction. 

PMID- 24863340
TI  - The chicken IL-1 family: evolution in the context of the studied vertebrate
      lineage.
AB  - The interleukin-1 gene family encodes a group of related proteins that exhibit a
      remarkable pleiotropy in the context of health and disease. The set of
      indispensable functions they control suggests that these genes should be found in
      all eukaryotic species. The ligands and receptors of this family have been
      primarily characterised in man and mouse. The genomes of most non-mammalian
      animal species sequenced so far possess all of the IL-1 receptor genes found in
      mammals. Yet, strikingly, very few of the ligands are identifiable in non
      mammalian genomes. Our recent identification of two further IL-1 ligands in the
      chicken warranted a critical reappraisal of the evolution of this vitally
      important cytokine family. This review presents substantial data gathered across
      multiple, divergent metazoan genomes to unambiguously trace the origin of these
      genes. With the hypothesis that all of these genes, both ligands and receptors,
      were formed in a single ancient ancestor, extensive database mining revealed
      sufficient evidence to confirm this. It therefore suggests that the emergence of
      mammals is unrelated to the expansion of the IL-1 family. A thorough review of
      this cytokine family in the chicken, the most extensively studied amongst non
      mammalian species, is also presented. 

PMID- 24863342
TI  - The effect of intermolecular interactions on the charge transport properties of
      thiazole/thiophene-based oligomers with trifluoromethylphenyl.
AB  - A fundamental understanding of the relationship between intermolecular
      interactions and transport properties in organic semiconducting materials is
      significant for their potential applications as electronic device element.
      Carrier transport properties of thiazole/thiophene-based oligomers with
      trifluoromethylphenyl groups 1, 2, and 3, in which the type and strength of the
      intermolecular interactions are different, were investigated within the framework
      of band model. The results show that pi-pi stacking interactions are mainly
      responsible for the hole transport, while hydrogen bonding interactions have a
      great influence on the electron transport. The specific transport mechanism could
      be explained by analyzing the density of states (DOS) and Gamma point wave
      functions. 

PMID- 24863343
TI  - Effects of substituents on tetracene derivatives on their stabilities and singlet
      fission.
AB  - Tetracene is well known for its high singlet fission (SF) efficiency, which could
      be used to enhance the energy conversion efficiency in solar cells. However, its
      photoinstability toward oxygen must be improved before it can be used as a light
      harvesting component. In this work, a series of substituted tetracenes were
      designed to identify tetracene compounds with not only good stability toward
      oxidation but also small SF activation energies. The stabilities were evaluated
      using the frontier molecular orbital energies, whereas the SF activation energies
      were deduced from the energy differences between the first excited singlet state
      and twice the first excited triplet state. Substitution strategies on tetracene
      are proposed for the purpose of simultaneously improving stability and reducing
      the SF activation energy. 

PMID- 24863345
TI  - Muscle ultrasonography for detecting fasciculations in frontotemporal dementia.
AB  - Ultrasound detection of muscle fasciculations was recently proposed for assessing
      lower motor neuron (LMN) dysfunction in ALS patients. Given the continuum between
      ALS and frontotemporal degeneration (FTD), the aim of the present study was to
      evaluate muscle ultrasound (MUS) in FTD both for feasibility and prevalence of
      fasciculations. Twenty-two FTD patients were examined (five muscles bilaterally:
      biceps brachii, first dorsalis interosseous, T10 paraspinalis, vastus lateralis,
      tibialis anterior) with a 7-MHz linear array transducer and a fasciculation score
      (FS) computed. Twenty-two matched cognitively-intact control subjects and six ALS
      patients were also included. Results showed that MUS was feasible, reliable and
      well tolerated in all subjects. Two FTD/MND patients displayed very high FS
      values, similar to those in ALS patients. The remaining 20 FTD patients displayed
      a mean FS value significantly higher than the control group with six patients
      (30%) having FS values out of the range of controls. Disease progression rate
      correlated with the FS. In conclusion, MUS can be easily applied to FTD patients
      and represents a non-invasive technique for defining LMN involvement in these
      patients. LMN dysfunction is a frequent condition in FTD and might identify a
      subset of patients with a different clinical course.

PMID- 24863344
TI  - The inhibitory effect of helenalin on telomerase activity is attributed to the
      alkylation of the CYS445 residue: evidence from QM/MM simulations.
AB  - Enhanced telomerase activity is a hallmark in the majority of cancer cells. Thus,
      understanding the interactions between telomerase and its inhibitors is
      fundamentally important for the development of novel anticancer drugs without
      severe side effects. In this study, the covalent binding of helenalin to CYS445
      of telomerase (PDB ID: 3DU6) was simulated using combined quantum chemical and
      molecular mechanical (QM/MM) methods. The results showed that the reaction was a
      reversible Michael-type addition and a hydrogen bond was formed between helenalin
      and the side chain of LYS416 of telomerase during the reaction procedure. The
      LYS416 residue is vital to telomere DNA recognition by interacting with DNA base
      through hydrogen bonds. The alkylation of CYS445 of telomerase by helenalin may
      interfere with the telomere DNA recognition at the telomerase active site, thus
      resulting in inhibition of the enzyme activity. 

PMID- 24863346
TI  - Neck pain disability is related to the frequency of migraine attacks: a cross
      sectional study.
AB  - BACKGROUND: Migraine and neck pain can be critical causes of disability. The
      contribution of neck pain for the overall disability of individuals with migraine
      remains unknown. OBJECTIVE: To contrast the disability experienced by individuals
      with episodic and chronic migraine with and without neck pain as captured by the
      Neck Disability Index. METHODS: Disability due to neck pain was assessed using
      the Neck Disability Index in individuals with episodic or chronic migraine seen
      at a university-based headache center. Neck disability was defined as mild (score
      ranging from 5 to 14 points), moderate (15-24 points), severe (25-34 points) or
      complete (35 points or higher). To compare differences between groups, a chi
      square test was applied. Log-binomial logistic regression was used to estimate
      disability as a function of headache status after adjustments for age, time since
      migraine onset, and headache intensity. RESULTS: Sample consisted of 169
      individuals, 104 with episodic migraine and 65 with chronic migraine. Any
      disability due to neck pain happened in 69% of those with episodic migraine,
      relative to 92% in chronic migraine (P < .001). Individuals with chronic migraine
      were at a significantly increased risk to have mild (RR = 2.5; CI 95% 1.1-6.1),
      moderate (RR = 3.7; CI 95% 1.5-8.8) and severe (RR = 5.1; CI 95%2.1-11.9)
      cervical disability relative to those with episodic migraine. Relative risks
      remained significant after adjustments. Time since episodic or chronic migraine
      onset significantly influenced the model (P = .035), but age and headache
      intensity did not (P = .27; P = .46). CONCLUSION: Neck pain significantly adds to
      the overall disability of individuals with episodic and chronic migraine.

PMID- 24863347
TI  - Application of glycerol as a foliar spray activates the defence response and
      enhances disease resistance of Theobroma cacao.
AB  - Previous work has implicated glycerol-3-phosphate (G3P) as a mobile inducer of
      systemic immunity in plants. We tested the hypothesis that the exogenous
      application of glycerol as a foliar spray might enhance the disease resistance of
      Theobroma cacao through the modulation of endogenous G3P levels. We found that
      exogenous application of glycerol to cacao leaves over a period of 4 days
      increased the endogenous level of G3P and decreased the level of oleic acid
      (18:1). Reactive oxygen species (ROS) were produced (a marker of defence
      activation) and the expression of many pathogenesis-related genes was induced.
      Notably, the effects of glycerol application on G3P and 18:1 fatty acid content,
      and gene expression levels, in cacao leaves were dosage dependent. A 100 mm
      glycerol spray application was sufficient to stimulate the defence response
      without causing any observable damage, and resulted in a significantly decreased
      lesion formation by the cacao pathogen Phytophthora capsici; however, a 500 mm
      glycerol treatment led to chlorosis and cell death. The effects of glycerol
      treatment on the level of 18:1 and ROS were constrained to the locally treated
      leaves without affecting distal tissues. The mechanism of the glycerol-mediated
      defence response in cacao and its potential use as part of a sustainable farming
      system are discussed. 

PMID- 24863348
TI  - TCM-based new drug discovery and development in China.
AB  - Over the past 30 years, China has significantly improved the drug development
      environment by establishing a series of policies for the regulation of new drug
      approval. The regulatory system for new drug evaluation and registration in China
      was gradually developed in accordance with international standards. The approval
      and registration of TCM in China became as strict as those of chemical drugs and
      biological products. In this review, TCM-based new drug discovery and development
      are introduced according to the TCM classification of nine categories. 

PMID- 24863349
TI  - Network pharmacology-based prediction and verification of the molecular targets
      and pathways for schisandrin against cerebrovascular disease.
AB  - AIM: To illuminate the molecular targets for schisandrin against cerebrovascular
      disease based on the combined methods of network pharmacology prediction and
      experimental verification. METHOD: A protein database was established through
      constructing the drug-protein network from literature mining data. The protein
      protein network was built through an in-depth exploration of the relationships
      between the proteins. The computational platform was implemented to predict and
      extract the sensitive sub-network with significant P-values from the protein
      protein network. Then the key targets and pathways were identified from the
      sensitive sub-network. The most related targets and pathways were also confirmed
      in hydrogen peroxide (H2O2)-induced PC12 cells by Western blotting. RESULTS:
      Twelve differentially expressed proteins (gene names: NFKB1, RELA, TNFSF10,
      MAPK1, CHUK, CASP8, PIGS2, MAPK14, CREB1, IFNG, APP, and BCL2) were confirmed as
      the central nodes of the interaction network (45 nodes, 93 edges). The NF-kappaB
      signaling pathway was suggested as the most related pathway of schisandrin for
      cerebrovascular disease. Furthermore, schisandrin was found to suppress the
      expression and phosphorylation of IKKalpha, as well as p50 and p65 induced by
      H2O2 in PC12 cells by Western blotting. CONCLUSION: The computational platform
      that integrates literature mining data, protein-protein interactions, sensitive
      sub-network, and pathway results in identification of the NF-kappaB signaling
      pathway as the key targets and pathways for schisandrin.

PMID- 24863350
TI  - Maslinic acid modulates glycogen metabolism by enhancing the insulin signaling
      pathway and inhibiting glycogen phosphorylase.
AB  - AIM: To investigate the molecular signaling mechanism by which the plant-derived,
      pentacyclic triterpene maslinic acid (MA) exerts anti-diabetic effects. METHOD:
      HepG2 cells were stimulated with various concentrations of MA. The effects of MA
      on glycogen phosphorylase a (GPa) activity and the cellular glycogen content were
      measured. Western blot analyses were performed with anti-insulin receptor beta
      (IRbeta), protein kinase B (also known as Akt), and glycogen synthase kinase
      3beta (GSK3beta) antibodies. Activation status of the insulin pathway was
      investigated using phospho-IRbeta, as well as phospho-Akt, and phospho-GSK3beta
      antibodies. The specific PI3-kinase inhibitor wortmannin was added to the cells
      to analyze the Akt expression. Enzyme-linked immunosorbent assay (ELISA) was used
      to measure the effect of MA on IRbeta auto-phosphorylation. Furthermore, the
      effect of MA on glycogen metabolism was investigated in C57BL/6J mice fed with a
      high-fat diet (HFD). RESULTS: The results showed that MA exerts anti-diabetic
      effects by increasing glycogen content and inhibiting glycogen phosphorylase
      activity in HepG2 cells. Furthermore, MA was shown to induce the phosphorylation
      level of IRbeta-subunit, Akt, and GSK3beta. The MA-induced activation of Akt
      appeared to be specific, since it could be blocked by wortmannin. Finally, MA
      treatment of mice fed with a high-fat diet reduced the model-associated adiposity
      and insulin resistance, and increased the accumulated hepatic glycogen content.
      CONCLUSION: The results suggested that maslinic acid modulates glycogen
      metabolism by enhancing the insulin signaling pathway and inhibiting glycogen
      phosphorylase.

PMID- 24863351
TI  - Alkaloids of Nitraria sibirica Pall. decrease hypertension and albuminuria in
      angiotensin II-salt hypertension.
AB  - In traditional Chinese medicine, Nitraria sibirica Pall. (Nitrariaceae) is used
      to treat hypertension. This study determined the effects of the total alkaloids
      of the leaves of Nitraria sibirica (NSTA) on blood pressure and albuminuria in
      mice treated with angiotensin II and a high-salt diet (ANG/HS). Adult mice were
      divided into three groups: control; infused with angiotensin II and fed a diet
      containing 4% NaCl (ANG/HS; and ANG/HS plus injection of NSTA (1 mg.kg(-1).d(-1),
      i.p.). After treatment of these regimens, daily water and food intake, kidney
      weight, blood pressure, urinary albumin excretion, renal concentrations of
      inflammatory markers, including soluble intercellular adhesion molecule-1 (sICAM
      1) and monocyte chemoattractant protein-1 (MCP-1), and the expression of renal
      fibrosis markers were determined. Compared to the control group, the ANG/HS group
      had higher blood pressure and urinary albumin excretion. Treatment with NSTA in
      ANG/HS mice for three weeks significantly reduced blood pressure and urinary
      albumin excretion. ANG/HS treatment caused elevated levels of sICAM-1 and MCP-1,
      as well as increased fibrosis markers. Concurrent treatment with ANG/HS and NSTA
      attenuated the levels and expression of renal inflammatory and fibrosis markers.
      Treatment with NSTA effectively reduces hypertension-induced albuminuria through
      the reduction of renal inflammatory and fibrosis markers. 

PMID- 24863352
TI  - Hepatoprotective and in vivo antioxidant activities of the hydroethanolic leaf
      extract of Mucuna pruriens (Fabaceae) in antitubercular drugs and alcohol models.
AB  - AIM: Hepatotoxicity is a significantly increasing health problem worldwide, and
      the extent of the problem has stimulated interest in the search for
      hepatotherapeutic agents from plants. This study investigated the
      hepatoprotective and in vivo antioxidant activities of the hydroethanolic extract
      of Mucuna pruriens leaves in antitubercular and alcohol-induced hepatotoxicity
      assays in rats. METHOD: In each of the models used, seven groups were allotted.
      The different groups received normal saline (10 mL.kg(-1), p.o.); hepatotoxicant
      (isoniazid-rifampicin, INH-RIF, 100 mg.kg(-1), i.p. or 20% ethanol 5 g.kg(-1),
      p.o.) and normal saline (10 mL.kg(-1), p.o.); hepatotoxicant and extract at doses
      of 100, 200, and 400 mg.kg(-1) p.o.; hepatotoxicant and silymarin 50 mg.kg(-1)
      p.o.; and extract at 400 mg.kg(-1) p.o. On the 21(st) day of treatment, blood was
      collected for assessment of serum biochemical parameters and harvested liver
      samples were assessed for antioxidants. RESULTS: The hepatotoxicants
      significantly (P < 0.05-0.001) increased the levels of alanine transaminase
      (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), bilirubin, and
      malondialdehyde (MDA); and reduced the levels of catalase (CAT), superoxide
      dismutase (SOD), glutathione peroxidase (GPx), and reduced glutathione GSH
      compared to control. M. pruriens significantly reversed (P < 0.05-0.001) the
      elevation in the level of ALT, AST, ALP, and bilirubin caused by the
      hepatotoxicants. The extract (200 and 400 mg.kg(-1)) significantly reversed (P <
      0.05) the diminution in the level of in vivo antioxidants and increased the level
      of MDA produced by INH-RIF. M. pruriens (100-400 mg.kg(-1)) elicited significant
      reduction (P < 0.001) in the level of MDA compared to the alcohol group.
      Silymarin also reversed the deleterious effects of the hepatotoxicants.
      CONCLUSION: The hydroethanolic extract of Mucuna pruriens leaves possesses
      hepatoprotective activity with enhancement of in vivo antioxidants as a possible
      mechanism of action.

PMID- 24863353
TI  - F-01A, an antibiotic, inhibits lung cancer cells proliferation.
AB  - AIM: In an effort to identify novel, small molecules which can affect the
      proliferation of lung cancer cells, F-01A, a polyether antibiotic isolated from
      the fermentation broth of Streptomyces was tested. METHOD: F-01A was tested for
      its antitumor properties on the lung cancer cell line SPC-A-1, at six doses (0.1,
      0.5, 1, 2.5, and 5 MUmol.L(-1)), using various cellular assays. Cell viability
      was measured by the MTT assay, Hochest 33258 was used to study nuclear
      morphology; DNA ladder and the loss of mitochondrial membrane potential were also
      evaluated. RESULTS: F-01A induces apoptosis against SPC-A-1 cells in a dose
      dependent manner. The IC50 is 0.65 MUmol.L(-1), and the inhibition at 5 MUmol.L(
      1) is 87.89%. Further, JC-1 staining indicates F-01A could induce the loss of
      mitochondrial membrane potential, and the DNA fragment is evident. CONCLUSION:
      Mechanistic analysis showed that F-01A induced apoptosis of cancer cells probably
      in the mitochondrial pathway. The antitumor actions of F-01A involve activation
      of the apoptotic pathway against SPC-A-1 cells, and it may be valuable for
      further drug development.

PMID- 24863354
TI  - Comparative evaluation of polysaccharides isolated from Astragalus, oyster
      mushroom, and yacon as inhibitors of alpha-glucosidase.
AB  - The incidence of diabetes has increased considerably, and become the third
      serious chronic disease following cancer and cardiovascular diseases. Though
      acarbose, metformin, and 1-deoxynojirimycin have good efficacy for clinical
      application as hypoglycemic drugs, their expensive costs and some degree of side
      effects have limited their clinical application. Recently, increasing attention
      has concentrated on the polysaccharides from natural plant and animal sources for
      diabetes. In order to illustrate the pharmaceutical activity of polysaccharides
      as natural hypoglycemic agents, polysaccharides isolated from Astragalus, oyster
      mushroom, and Yacon were evaluated for their inhibitory effects on alpha
      glucosidase. Polysaccharides were extracted and purified from Astragalus, Oyster
      mushroom, and Yacon with hot water at 90  degrees C for 3 h, respectively. The
      total sugar content of the polysaccharide was determined by the phenol-sulfuric
      acid method. The alpha-glucosidase inhibitory activity was measured by the
      glucose oxidase method. The results exhibited that the inhibitory effects on
      alpha-glucosidase were in decreasing order, Astragalus > oyster mushroom > Yacon.
      The alpha-glucosidase inhibition percentage of Astragalus polysaccharide and
      oyster mushroom polysaccharide were over 40% at the polysaccharide concentration
      of 0.4 mg.mL(-1). The IC50 of Astragalus polysaccharide and oyster mushroom
      polysaccharide were 0.28 and 0.424 mg.mL(-1), respectively. The information
      obtained from this work is beneficial for the use polysaccharides as a dietary
      supplement for health foods and therapeutics for diabetes. 

PMID- 24863355
TI  - New 9, 19-cycloartane triterpenoid from the root of Cimicifuga foetida.
AB  - AIM: To study the 9, 19-cycloartane triterpenes from the roots of Cimicifuga
      foetida. METHOD: Chromatographic separations by silica gel, C18 reversed phase
      silica gel, and high-performance liquid chromatography (HPLC) were used. All of
      the structures were elucidated on the basis of spectroscopic analysis and
      chemical methods. RESULTS: Five 9, 19-cycloartane triterpenes, (3beta, 12beta,
      15alpha, 24R)-12, 2'-diacetoxy-24, 25-epoxy-15-hydroxy-16, 23-dione-3-O-alpha-L
      arabinopyranoside (1), actein (2), 23-epi-26-deoxyactein (3), asiaticoside B (4),
      and 12beta-hydroxycimigenol (5) were isolated from the roots of Cimicifuga
      foetida. CONCLUSION: Compound 1 is a new triterpene with two acetoxy groups at C
      2' and C-12.

PMID- 24863356
TI  - A new diterpene from the stems of Trigonostemon heterophyllus.
AB  - AIM: To investigate the chemical constituents in the stems of Trigonostemon
      heterophyllus. METHOD: The chemical constituents were isolated by column
      chromatography on silica gel, Rp-18, and Sephadex LH-20, and their structures
      were elucidated on the basis of spectroscopic analysis. RESULTS: Three compounds
      were isolated and identified as a new diterpene, trigonoheterene B (1), together
      with two known compounds, trigonostemone (2) and trigonochinene B (3).
      CONCLUSION: Compound 1 is new. Compounds 2 and 3 showed antibacterial activities.

PMID- 24863357
TI  - Chemical constituents from the stems of Gymnema sylvestre.
AB  - AIM: To study the chemical constituents of stems of Gymnema sylvestre (Retz.)
      Schult. METHODS: Chromatographic techniques using silica gel, C18 reversed phase
      silica gel, and prep-HPLC were used. The structures were elucidated on the basis
      of MS and spectroscopic analysis (1D and 2D NMR), as well as chemical methods.
      RESULTS: Seven compounds were isolated and their structures were elucidated as
      conduritol A (1), stigmasterol (2), lupeol (3), stigmasterol-3-O-beta-D-glucoside
      (4), the sodium salt of 22alpha-hydroxy-longispinogenin-3-O-beta-D-glucopyranosyl
      (1->3)-beta-D-glu-curono-pyranosyl-28-O-alpha-L-rhamnopyranoside (5), oleanolic
      acid-3-O-beta-D-glucopyranosyl-(1->6)-beta-D-glucopyranoside (6), and the sodium
      salt of 22alpha-hydroxy-longispinogenin 3-O-beta-D-glucuronopyranosyl-28-O-alpha
      L-rhamnopyranoside (7). The inhibition activities of compounds 1, 5-7 on non
      enzymatic glycation of protein in vitro were evaluated. CONCLUSION: Compound 7 is
      a new triterpenoid saponin. It was shown that compounds 1, 5-7 have weak
      inhibition activities for non-enzymatic glycation of protein in vitro.

PMID- 24863358
TI  - A new saikogenin from the roots of Bupleurum bicaule.
AB  - AIM: To study the chemical constituents from the roots of Buleurum bicaule Helm
      (Apiaceae). METHOD: Silica gel, Sephadex LH-20, MPLC Rp-C18 column
      chromatography, and HPLC were used for isolation of compounds. The structures
      were elucidated on the basis of 1D- and 2D-NMR technology and HRESI-MS. Compounds
      were evaluated in vitro for their inhibitory ability against the proliferation of
      rat mesangial cells by the MTT method. RESULTS: Twelve compounds were isolated,
      and their structures were identified on the basis of their spectroscopic and
      physico-chemical properties as 13, 28-epoxy-olean-11-en-3-one (1), saikogenin E
      (2), saikogenin G (3), 11alpha-methoxy-3beta, 16beta, 23, 28-tetrahydroxyolean-12
      ene (4), saikogenin D (5), prosaikogenin F (6), prosaikogenin A (7),
      prosaikogenin G (8), prosaikogenin D (9), laccaic acid (10b), methyl gallate
      (11), and ethyl gallate (12). Compounds 1, 2, 7, 8, and 10 were observed to have
      inhibitory activity against mesangial cell proliferationin to different degrees.
      CONCLUSION: Compound 1, 8, and 10 exhibit significant inhibitory effects on rat
      mesangial cell proliferation induced by Ang II.

PMID- 24863359
TI  - Anti-methicillin-resistant Staphylococcus aureus assay of azalomycin F5a and its
      derivatives.
AB  - AIM: To discover anti-methicillin-resistant Staphylococcus aureus (anti-MRSA)
      microbial natural products or their derivatives. METHOD: Azalomycin F5a (1) was
      prepared through fermentation of Streptomyces hygroscopicus var. azalomyceticus,
      and its derivatives were synthesized through hydrocarbylation in hydrocarbyl
      alcoholic-AcOH (4 : 1) and subsequent demalonylation with 2 mol.L(-1) KOH in MeOH
      H2O (7 : 3). Their activities against MRSA ATCC 33592 and three clinical MRSA
      isolates were evaluated by the agar diffusion and broth microdilution methods.
      RESULTS: Four demalonylazalomycin F5a derivatives 2 to 5 were synthesized. The
      anti-MRSA activity assay indicated that compounds 1 to 5 showed remarkable
      activity against MRSA, and their minimum inhibitory concentrations (MICs) were
      respectively 3.0-4.0, 0.5-1.0, 0.67-1.0, 0.67-0.83, and 0.5-0.83 MUg.mL(-1).
      CONCLUSION: Azalomycin F5a and the demalonylazalomycin F5a derivatives 2-5 showed
      remarkable anti-MRSA activity, and the anti-MRSA activities of 2 to 5 were higher
      than that of 1, while the anti-MRSA activities of 2 to 5 showed no obvious
      differences. It was also shown that the malonyl monoester group of azalomycin F5a
      was less important for its anti-MRSA activity.

PMID- 24863360
TI  - Transformation of astragalosides from radix astragali under acidic, neutral, and
      alkaline extraction conditions monitored by LC-ESI-TOF/MS.
AB  - AIM: To reveal the profile of astragalosides for better quality evaluation of
      Radix Astragali, this study was aimed to investigate the transformation of
      astragalosides under different conditions. METHOD: Seven major astragalosides
      were selected for evaluation under acidic, neutral and alkaline conditions. The
      transformation in real plant samples was also examined and the products were
      characterized by LC-ESI-TOF/MS. RESULTS: In weak acidic solution, all of the
      astragalosides are stable. In addition, the transformation ratios of the
      astragalosides under neutral and alkaline conditions were also obtained.
      CONCLUSION: In neutral solution, malonylastragaloside I was transformed to
      astragaloside I; and in alkaline solution, substituent group(s) in the xylose
      moiety of all the astragalosides were eliminated. Since astragalosdie IV is the
      basic skeleton structure of the astrgalosides, it is a common transformation
      product of other astragalosides.

PMID- 24863361
TI  - Sequential combination of karyotyping and RNA-sequencing in the search for cancer
      specific fusion genes.
AB  - Cancer-specific fusion genes are often caused by cytogenetically visible
      chromosomal rearrangements such as translocations, inversions, deletions or
      insertions, they can be the targets of molecular therapy, they play a key role in
      the accurate diagnosis and classification of neoplasms, and they are of
      prognostic impact. The identification of novel fusion genes in various neoplasms
      therefore not only has obvious research importance, but is also potentially of
      major clinical significance. The "traditional" methodology to detect them began
      with cytogenetic analysis to find the chromosomal rearrangement, followed by
      utilization of fluorescence in situ hybridization techniques to find the probe
      which spans the chromosomal breakpoint, and finally molecular cloning to localize
      the breakpoint more precisely and identify the genes fused by the chromosomal
      rearrangement. Although laborious, the above-mentioned sequential approach is
      robust and reliable and a number of fusion genes have been cloned by such means.
      Next generation sequencing (NGS), mainly RNA sequencing (RNA-Seq), has opened up
      new possibilities to detect fusion genes even when cytogenetic aberrations are
      cryptic or information about them is unknown. However, NGS suffers from the
      shortcoming of identifying as "fusion genes" also many technical, biological and,
      perhaps in particular, clinical "false positives," thus making the assessment of
      which fusions are important and which are noise extremely difficult. The best way
      to overcome this risk of information overflow is, whenever reliable cytogenetic
      information is at hand, to compare karyotyping and sequencing data and
      concentrate exclusively on those suggested fusion genes that are found in
      chromosomal breakpoints. This article is part of a Directed Issue entitled: Rare
      Cancers. 

PMID- 24863364
TI  - Exciton coupling of surface complexes on a nanocrystal surface.
AB  - Exciton coupling may arise when chromophores are brought into close spatial
      proximity. Herein the intra-nanocrystal exciton coupling of the surface complexes
      formed by coordination of 8-hydroxyquinoline to ZnS nanocrystals (NCs) is
      reported. It is studied by absorption, photoluminescence (PL), PL excitation
      (PLE), and PL lifetime measurements. The exciton coupling of the surface
      complexes tunes the PL color and broadens the absorption and PLE windows of the
      NCs, and thus is a potential strategy for improving the light-harvesting
      efficiency of NC solar cells and photocatalysts. 

PMID- 24863363
TI  - Halophilic bacteria are colonizing the exhibition areas of the Capuchin Catacombs
      in Palermo, Italy.
AB  - The Capuchin Catacombs of Palermo, Italy, contain over 1800 mummies dating from
      the 16th to 20th centuries AD. Their environment is not conducive to the
      conservation of the remains due to, among other factors, water infiltration,
      which is producing salt efflorescences on the walls. A multiphasic approach was
      applied to investigate the halophilic microbiota present in the Catacombs.
      Enrichment cultures were conducted on media containing different NaCl
      concentrations, ranging from 3 to 20 %. For screening of the strains, the
      following two PCR-based methods were used and compared: fluorescence internal
      transcribed spacer PCR (f-ITS) and random amplification of polymorphic DNA (RAPD)
      analyses. Results derived from RAPD profiles were shown to be slightly more
      discriminative than those derived from f-ITS. In addition, the proteolytic and
      cellulolytic abilities were screened through the use of plate assays, gelatin
      agar and Ostazin Brilliant Red H-3B (OBR-HEC), respectively. Many of the strains
      isolated from the wall samples displayed proteolytic activities, such as all
      strains belonging to the genera Bacillus, Virgibacillus and Arthrobacter, as well
      as some strains related to the genera Oceanobacillus, Halobacillus and
      Idiomarina. In addition, many of the strains isolated from materials employed to
      stuff the mummies showed cellulolytic activities, such as those related to
      species of the genera Chromohalobacter and Nesterenkonia, as well as those
      identified as Staphylococcus equorum and Halomonas sp. Furthermore, many of the
      strains were pigmented ranging from yellow to a strong pink color, being directly
      related to the discoloration displayed by the materials.

PMID- 24863362
TI  - Mitochondria in monocytes and macrophages-implications for translational and
      basic research.
AB  - The mitochondrion plays a crucial role in the immune system particularly in
      regulating the responses of monocytes and macrophages to tissue injury,
      pathogens, and inflammation. In systemic diseases such as atherosclerosis and
      chronic kidney disease (CKD), it has been established that disruption of monocyte
      and macrophage function can lead to chronic inflammation. Polarization of
      macrophages into the pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes
      results in distinct metabolic reprograming which corresponds to the progression
      and resolution of inflammation. In this review, we will discuss the role of the
      mitochondrion in monocyte and macrophage function and how these cells
      specifically influence the pathophysiology of atherosclerosis and CKD. We propose
      that assessing monocyte bioenergetics in different disease states could (1)
      enhance our understanding of the energetic perturbations occurring in systemic
      inflammatory conditions and (2) aid in identifying therapeutic interventions to
      mitigate these disorders in patients. 

PMID- 24863365
TI  - Estimation of migration rates from marker-based parentage analysis.
AB  - Coupled with rapid developments of efficient genetic markers, powerful population
      genetic methods were proposed to estimate migration rates (m) in natural
      populations in much broader spatial and temporal scales than the traditional mark
      release-recapture (MRR) methods. Highly polymorphic (e.g. microsatellites) and
      genomic-wide (e.g. SNPs) markers provide sufficient information to assign
      individuals to their populations or parents of origin and thereby to estimate
      directly m in a way similar to MRR. Such direct estimates of current migration
      rates are particularly useful in understanding the ecology and microevolution of
      wild populations and in managing the populations in the future. In this study, I
      proposed and implemented, in the software MigEst, a likelihood method to use
      marker-based parentage assignments in jointly estimating m and candidate parent
      sampling proportions (x) in a subset of populations, investigated its power and
      accuracy using data simulated in various scenarios of population properties (e.g.
      the actual m, number, size and differentiation of populations) and sampling
      properties (e.g. the numbers of sampled parent candidates, offspring and
      markers), compared it with the population assignment approach implemented in the
      software BayesAss and demonstrated its usefulness by analysing a microsatellite
      data set from three natural populations of Brazilian bats. Simulations showed
      that MigEst provides unbiased and accurate estimates of m and performs better
      than BayesAss except when populations are highly differentiated with very small
      and ecologically insignificant migration rates. A valuable property of MigEst is
      that in the presence of unsampled populations, it gives good estimates of the
      rate of migration among sampled populations as well as of the rate of migration
      into each sampled population from the pooled unsampled populations.

PMID- 24863366
TI  - Virulent bacterial infection improves aversive learning performance in Drosophila
      melanogaster.
AB  - Virulent infections are expected to impair learning ability, either as a direct
      consequence of stressed physiological state or as an adaptive response that
      minimizes diversion of energy from immune defense. This prediction has been well
      supported for mammals and bees. Here, we report an opposite result in Drosophila
      melanogaster. Using an odor-mechanical shock conditioning paradigm, we found that
      intestinal infection with bacterial pathogens Pseudomonas entomophila or Erwinia
      c. carotovora improved flies' learning performance after a 1h retention interval.
      Infection with P. entomophila (but not E. c. carotovora) also improved learning
      performance after 5 min retention. No effect on learning performance was detected
      for intestinal infections with an avirulent GacA mutant of P. entomophila or for
      virulent systemic (hemocoel) infection with E. c. carotovora. Assays of
      unconditioned responses to odorants and shock do not support a major role for
      changes in general responsiveness to stimuli in explaining the changes in
      learning performance, although differences in their specific salience for
      learning cannot be excluded. Our results demonstrate that the effects of
      pathogens on learning performance in insects are less predictable than suggested
      by previous studies, and support the notion that immune stress can sometimes
      boost cognitive abilities.

PMID- 24863367
TI  - Analysis of carbohydrates and glycoconjugates by matrix-assisted laser
      desorption/ionization mass spectrometry: an update for 2009-2010.
AB  - This review is the sixth update of the original article published in 1999 on the
      application of MALDI mass spectrometry to the analysis of carbohydrates and
      glycoconjugates and brings coverage of the literature to the end of 2010. General
      aspects such as theory of the MALDI process, matrices, derivatization, MALDI
      imaging, arrays and fragmentation are covered in the first part of the review and
      applications to various structural typed constitutes the remainder. The main
      groups of compound that are discussed in this section are oligo and
      polysaccharides, glycoproteins, glycolipids, glycosides and biopharmaceuticals.
      Many of these applications are presented in tabular form. Also discussed are
      medical and industrial applications of the technique, studies of enzyme reactions
      and applications to chemical synthesis.

PMID- 24863368
TI  - Microbiota dynamics related to environmental conditions during the fermentative
      production of Fen-Daqu, a Chinese industrial fermentation starter.
AB  - Chinese Daqu is used as a starter for liquor and vinegar fermentations. It is
      produced by solid state fermentation of cereal-pulse mixtures. A succession of
      fungi, lactic acid bacteria and Bacillus spp. was observed during the production
      of Daqu. Mesophilic bacteria followed by fungi, dominated the first phase of
      fermentation. Next, lactic acid bacteria increased in relative abundance,
      resulting in an increase of the acidity of Daqu. At the final stages of
      fermentation, Bacillus spp. and thermophilic fungi became the dominant groups,
      possibly due to their tolerance to low water activity and high temperature. Both
      culture-dependent and culture-independent analyses confirmed that Bacillus spp.
      were ubiquitous throughout the process. Yeast species such as Wickerhamomyces
      anomalus, Saccharomycopsis fibuligera and Pichia kudriavzevii were present
      throughout almost the entire fermentation process, but the zygomycetous fungus
      Lichtheimia corymbifera proliferated only during the final stages of
      fermentation. Canonical correspondence analysis (CCA) revealed the significance
      of acidity, moisture content and temperature in correlation with the composition
      of the microbial communities at different stages. 

PMID- 24863369
TI  - Driving anger in Malaysia.
AB  - The present study examined the types of situations that cause Malaysian drivers
      to become angry. The 33-item version of the driver anger scale (Deffenbacher et
      al., 1994) was used to investigate driver anger amongst a sample of 339 drivers.
      Confirmatory factor analysis showed that the fit of the original six-factor model
      (discourtesy, traffic obstructions, hostile gestures, slow driving, illegal
      driving and police presence), after removing one item and allowing three error
      pairs to covary, was satisfactory. Female drivers reported more anger, than
      males, caused by traffic obstruction and hostile gestures. Age was also
      negatively related to five (discourtesy, traffic obstructions, hostile gestures,
      slow driving and police presence) of the six factors and also to the total DAS
      score. Furthermore, although they were not directly related to crash involvement,
      several of the six forms of driving anger were significantly related to the crash
      related conditions of: near misses, loss of concentration, having lost control of
      a vehicle and being ticketed. Overall the pattern of findings made in the present
      research were broadly similar to those from Western countries, indicating that
      the DAS is a valid measure of driving anger even among non-European based
      cultures. 

PMID- 24863370
TI  - Conformational modulation and hydrodynamic radii of CP12 protein and its
      complexes probed by fluorescence correlation spectroscopy.
AB  - Light/dark regulation of the Calvin cycle in oxygenic photosynthetic organisms
      involves the formation and dissociation of supramolecular complexes between CP12,
      a nuclear-encoded chloroplast protein, and the two enzymes glyceraldehyde-3
      phosphate dehydrogenase (GAPDH) (EC 1.2.1.13) and phosphoribulokinase (PRK) (EC
      2.7.1.19). Despite the high importance of understanding the structural basis of
      the interaction of CP12 with GAPDH and PRK to investigate the regulation of the
      Calvin cycle, information is still lacking about the structural remodulation of
      CP12 and its complex formation. Here, we characterize the diffusion dynamics and
      hydrodynamic radii of CP12 from Chlamydomonas reinhardtii upon binding to GAPDH
      and PRK using fluorescence correlation spectroscopy experiments. We quantify a
      hydrodynamic radius of 3.4 +/- 0.2 nm for the CP12 protein with an increase up to
      5.2 +/- 0.3 nm upon complex formation with GAPDH and PRK. In addition, unfolding
      experiments reveal a 1.6- and 2.0-fold increase respectively of the hydrodynamic
      radii for the N-terminal and C-terminal cysteine CP12 mutant proteins compared
      with their native folded structures. The different behavior of the CP12 mutant
      proteins during hydrophobic collapse transition is a direct clue to different
      structural orientations of the CP12 mutant proteins. These different structures
      are expected to facilitate the binding of either GAPDH or PRK during binary
      complex and ternary complex formation.

PMID- 24863371
TI  - Gas chromatographic-mass spectrometric analysis and subsequent quality
      improvement of plastic infusion packaging materials.
AB  - Although the opalescence of sterile transparent plastic materials utilized for
      the packaging of parenteral infusion drugs is a serious quality problem, most
      suppliers do not report the exact compositions of such polymers, and no
      literature data are available. Similarly, no information is available as concerns
      the potential incompatibility of the inner bag and the overpouch. Our gas
      chromatographic-mass spectrometric study revealed that the cause of the
      opalescence is the presence of a low-molecular-weight slip additive, 13
      docosenamide (erucamide), which is transferred into the primary infusion bag from
      the overpouch during the heat-sterilization process. Autoclaving trials confirmed
      the analytical results. In view of these findings, a new slip additive-free
      overpouch has been produced as secondary packaging material, which does not give
      rise to opalescence. 

PMID- 24863372
TI  - Development and validation of a stability-indicating LC-UV method for the
      determination of pantethine and its degradation product based on a forced
      degradation study.
AB  - Pantethine (d-bis-(N-pantothenyl-beta-aminoethyl)-disulfide, PAN), the stable
      disulfide form of pantetheine, has beneficial effects in vascular diseases being
      able to decrease the hyperlipidaemia, moderate the platelet function and prevent
      the lipid peroxidation. Furthermore, recent studies suggested that PAN may be an
      effective therapeutic agent for cerebral malaria and, possibly, for
      neurodegenerative processes. Interestingly, in the literature, there were no data
      dealing with the chemical stability and the analytical aspects of PAN. Hence, in
      the present work the chemical stability of PAN was for the first time established
      through a forced degradation study followed by liquid chromatography tandem mass
      spectrometry investigation showing the formation of three degradation products of
      PAN (PD1, PD2 and POx) arising from hydrolytic, thermal and oxidative stresses.
      Based on these data a stability-indicating LC-UV method for simultaneous
      estimation of PAN, and its most relevant degradation product (PD1) was developed
      and validated; moreover the method allowed also the separation and the
      quantification of the preservative system, constituted by a paraben mixture. The
      method showed linearity for PAN (0.4-1.2mgmL(-1)), MHB, PHB (0.4-1.2MUgmL(-1))
      and PD1 (2.5-100MUgmL(-1)); the precision, determined in terms of intra-day and
      inter-day precision, expressed as RSDs, were in the ranges 0.4-1.2 and 0.7-1.4,
      respectively. The method demonstrated to be accurate and robust; indeed the
      average recoveries were 100.2, 99.9, and 100.0% for PAN, MHB and PHB,
      respectively, and 99.9% for PD1. By applying small variations of the mobile phase
      composition, counter-ion concentration and pH the separation of analytes was not
      affected. Finally, the applicability of this method was evaluated analyzing the
      available commercial forms at release as well as during stability studies. 

PMID- 24863373
TI  - Plasma metabolic profiling analysis of nephrotoxicity induced by acyclovir using
      metabonomics coupled with multivariate data analysis.
AB  - Acyclovir (ACV) is an antiviral agent. However, its use is limited by adverse
      side effect, particularly by its nephrotoxicity. Metabonomics technology can
      provide essential information on the metabolic profiles of biofluids and organs
      upon drug administration. Therefore, in this study, mass spectrometry-based
      metabonomics coupled with multivariate data analysis was used to identify the
      plasma metabolites and metabolic pathways related to nephrotoxicity caused by
      intraperitoneal injection of low (50mg/kg) and high (100mg/kg) doses of
      acyclovir. Sixteen biomarkers were identified by metabonomics and nephrotoxicity
      results revealed the dose-dependent effect of acyclovir on kidney tissues. The
      present study showed that the top four metabolic pathways interrupted by
      acyclovir included the metabolisms of arachidonic acid, tryptophan, arginine and
      proline, and glycerophospholipid. This research proves the established
      metabonomic approach can provide information on changes in metabolites and
      metabolic pathways, which can be applied to in-depth research on the mechanism of
      acyclovir-induced kidney injury. 

PMID- 24863374
TI  - Cell type-specific qualitative and quantitative analysis of saikosaponins in
      three Bupleurum species using laser microdissection and liquid chromatography
      quadrupole/time of flight-mass spectrometry.
AB  - Cell type-specific metabolite analysis is a promising method for understanding
      plant metabolite production, function, transport and storage. In the present
      study, laser microdissection (LMD) and ultra-high performance liquid
      chromatography quadrupole/time of flight-mass spectrometry are combined to
      determine where secondary metabolites are accumulated in the roots of Bupleurum
      scorzonerifolium Willd, Bupleurum chinense DC. and Bupleurum falcatum L. Four
      tissues, namely cork, cortex, phloem and xylem, were microdissected by laser
      microdissection, and their chemical profiles were analyzed. The main metabolites
      are saikosaponins. Different tissues contained different saikosaponins.
      Generally, the cork and cortex from all three species contained more types of
      saikosaponins and higher contents of saikosaponins a, c and d than did the phloem
      and xylem. Interestingly, in the roots of Bupleurum scorzonerifolium and B.
      falcatum, the cork contained much higher contents of saikosaponins a, c and d
      than did the cortex; while in the root of B. chinense, the cortex contained
      higher contents of saikosaponins a, c and d than the cork. Explanation and
      application of the results are discussed. The present findings yield valuable
      insights into the quality evaluation of Bupleuri Radix by morphological features.

PMID- 24863375
TI  - Multifocal motor neuropathy with high titers of anti-MAG antibodies.
AB  - Multifocal motor neuropathy (MMN) and anti-myelin-associated glycoprotein (anti
      MAG)-associated neuropathy are clinically and electrophysiologically distinct
      entities. We describe a patient with characteristic features of both
      neuropathies, raising the possibility of an overlap syndrome. A 49-year-old
      patient reported a history of slowly progressive predominantly distal
      tetraparesis, with mild sensory deficits. Nerve conduction studies demonstrated
      persistent motor conduction blocks outside compression sites, typical of MMN.
      Laboratory findings revealed persistently high titers of anti-MAG immunoglobulin
      Mlambda (IgMlambda) paraprotein in the context of a monoclonal gammapathy of
      unknown significance. Skin biopsy of distal lower limb revealed IgM positive
      terminal nerve perineurium deposits. This case suggests that the distinction
      between subtypes of chronic inflammatory neuropathies may not be as clear as
      initially thought, and that the pattern of pathogenicity of anti-MAG antibodies
      may vary. 

PMID- 24863376
TI  - Pre-drinking and alcohol-related harm in undergraduates: the influence of
      explicit motives and implicit alcohol identity.
AB  - The present study investigated how pre-drinking could be explained using a model
      based on dual-systems theory, incorporating measures of explicit and implicit
      constructs. Undergraduate students (N = 144; 44 male; 100 female; M age = 20.1
      years), completed an online survey comprising measures of pre-drinking motives, a
      measure of pre-drinking cost motives, and an alcohol identity implicit
      association test. Variance-based structural equation modelling revealed that the
      predictors explained 34.8% of the variance in typical pre-drinking alcohol
      consumption and 25% of the variance in alcohol-related harm. Cost, interpersonal
      enhancement, and barriers to consumption motives predicted higher typical pre
      drinking alcohol consumption and greater alcohol-related harm. Higher situational
      control scores predicted lower typical pre-drinking alcohol consumption, and
      lower alcohol-related harm. Positive implicit alcohol identity predicted alcohol
      related harm, but not typical alcohol consumption. Results indicate that a dual
      systems approach to pre-drinking has utility in predicting alcohol-related harm
      and may inform interventions to reduce excessive alcohol consumption and
      associated harm.

PMID- 24863377
TI  - A detailed representation of electrostatic energy in prediction of sequence and
      pH dependence of protein stability.
AB  - A molecular mechanics model, previously validated in applications to structure
      prediction, is shown to reproduce experiment in predictions of protein ionization
      state, and in predictions of sequence and pH dependence of protein stability.
      Over a large dataset, 1876 values of DeltaDeltaG of folding, the RMSD is 1.34
      kcal/mol. Using an alternative measure of accuracy, either the sign of the
      calculated DeltaDeltaG agrees with experiment or the absolute value of the
      deviation is less than 1.0 kcal/mol, 1660 of 1876 data points (88.5%) pass the
      condition. Relative to models used previously in computer-aided protein design,
      the concept, we propose, most responsible for the performance of our model, and
      for the extensibility to non-neutral values of pH, is the treatment of
      electrostatic energy. The electronic structure of the protein is modeled using
      distributed atomic multipoles. The structured liquid state of the solvent is
      modeled using a dielectric continuum. A modification to the energetics of the
      reaction field, induced by the protein in the dielectric continuum, attempts to
      account for preformed multipoles of solvent water molecules and ions. An
      adjustable weight (with optimal value.141) applied to the total vacuum energy
      accounts implicitly for electronic polarization. A threshold distance, beyond
      which pairwise atomic interactions are neglected, is not used. In searches
      through subspaces of sequences and conformations, efficiency remains acceptable
      for useful applications.

PMID- 24863378
TI  - Our 2014 approach to candidaemia.
AB  - Candidaemia remains a relevant challenge in everyday patient care on intensive
      care units and general wards. Delays to adequate treatment increase mortality
      rates and institutional standard operating procedures facilitate optimal
      treatment. A positive blood culture requires immediate treatment. Echinocandins
      are the first-line drugs of choice. Indwelling catheters have to be removed if
      feasible. Daily blood cultures until persistently negative exclude ongoing
      fungaemia. In case of Candida parapsilosis antifungal therapy should be switched
      to intravenous fluconazole. After 10 days of intravenous either echinocandin or
      fluconazole treatment, step-down to oral application of fluconazole simplifies
      antifungal therapy. Depending on organ involvement and clinical presentation of
      the patient antifungal treatment should be continued for at least 14 days after
      the last positive blood culture. We present our institutional management
      algorithm for candidaemia which is based on current guidelines and
      recommendations to improve patient outcome.

PMID- 24863379
TI  - Diabetes: Predicting renal function decline in patients with T2DM.

PMID- 24863385
TI  - Risk factors: Prepregnancy GGT levels predict risk of gestational diabetes
      mellitus.

PMID- 24863383
TI  - Glucocorticoids and fetal programming part 2: Mechanisms.
AB  - The lifelong health of an individual is shaped during critical periods of
      development. The fetus is particularly susceptible to internal and external
      stimuli, many of which can alter developmental trajectories and subsequent
      susceptibility to disease. Glucocorticoids are critical in normal development of
      the fetus, as they are involved in the growth and maturation of many organ
      systems. The surge in fetal glucocorticoid levels that occurs in most mammalian
      species over the last few days of pregnancy is an important developmental switch
      leading to fundamental changes in gene regulation in many organs, including the
      brain. These changes are important for the transition to postnatal life. Exposure
      of the fetus to increased levels of glucocorticoids, resulting from maternal
      stress or treatment with synthetic glucocorticoids, can lead to long-term
      'programming' of hypothalamic-pituitary-adrenal function and behaviours.
      Glucocorticoids act at multiple levels within the fetal brain. Growing evidence
      indicates that they can exert powerful effects on the epigenome, including on DNA
      methylation, histone acetylation and microRNA, to influence gene expression. Such
      influences probably represent a critical component of the 'programming' process,
      and might be partly responsible for the transgenerational effects of antenatal
      glucocorticoid exposure on neurologic, cardiovascular and metabolic function. 

PMID- 24863388
TI  - A selective release system based on dual-drug-loaded mesoporous silica for
      nanoparticle-assisted combination therapy.
AB  - A selective release system was demonstrated with a dual-cargo loaded MSNs. When
      stimulated by different signals (UV or H(+)), this system could selectively
      release different kinds of cargoes individually. Furthermore, this system has
      been used to provide a combination of chemotherapy and biotherapy for cancer
      treatment. This controlled release system could be an important step in the
      development of more effective and sophisticated nanomedicine and nanodevices, due
      to the possibility of selective release of a complex multi-drug.

PMID- 24863389
TI  - Facing head and neck cancer deaths head on: lessons for survival.

PMID- 24863382
TI  - Glucocorticoids and fetal programming part 1: Outcomes.
AB  - Fetal development is a critical period for shaping the lifelong health of an
      individual. However, the fetus is susceptible to internal and external stimuli
      that can lead to adverse long-term health consequences. Glucocorticoids are an
      important developmental switch, driving changes in gene regulation that are
      necessary for normal growth and maturation. The fetal hypothalamic-pituitary
      adrenal (HPA) axis is particularly susceptible to long-term programming by
      glucocorticoids; these effects can persist throughout the life of an organism.
      Dysfunction of the HPA axis as a result of fetal programming has been associated
      with impaired brain growth, altered behaviour and increased susceptibility to
      chronic disease (such as metabolic and cardiovascular disease). Moreover, the
      effects of glucocorticoid-mediated programming are evident in subsequent
      generations, and transmission of these changes can occur through both maternal
      and paternal lineages. 

PMID- 24863387
TI  - Circadian clock control of endocrine factors.
AB  - Organisms experience dramatic fluctuations in demands and stresses over the
      course of the day. In order to maintain biological processes within physiological
      boundaries, mechanisms have evolved for anticipation of, and adaptation to, these
      daily fluctuations. Endocrine factors have an integral role in homeostasis. Not
      only do circulating levels of various endocrine factors oscillate over the 24 h
      period, but so too does responsiveness of target tissues to these signals or
      stimuli. Emerging evidence suggests that these daily endocrine oscillations do
      not occur solely in response to behavioural fluctuations associated with sleep
      wake and feeding-fasting cycles, but are orchestrated by an intrinsic timekeeping
      mechanism known as the circadian clock. Disruption of circadian clocks by genetic
      and/or environmental factors seems to precipitate numerous common disorders,
      including the metabolic syndrome and cancer. Collectively, these observations
      suggest that strategies designed to realign normal circadian rhythmicities hold
      potential for the treatment of various endocrine-related disorders. 

PMID- 24863391
TI  - Prognostic significance of cytoskeleton-associated membrane protein 4 and its
      palmitoyl acyltransferase DHHC2 in hepatocellular carcinoma.
AB  - BACKGROUND: The functions of cytoskeleton-associated membrane protein 4 (CKAP4),
      one kind of type II transmembrane protein, are associated with the palmitoyl
      acyltransferase DHHC2. The objective of the current study was to investigate
      CKAP4/DHHC2 expression and its prognostic significance in patients with
      hepatocellular carcinoma (HCC). METHODS: Two independent cohorts of 416 patients
      with HCC were enrolled. All the patients included had defined clinicopathologic
      and follow-up data. Using real-time polymerase chain reaction and
      immunohistochemical assay, CKAP4 and DHHC2 expression were evaluated. The
      association between CKAP4/DHHC2 expression and HCC-specific disease-free survival
      and overall survival was analyzed by Kaplan-Meier curves, the log-rank test, and
      Multivariate Cox regression analyses. RESULTS: The data documented that CKAP4
      expression was much higher in HCC tumor tissues compared with adjacent normal
      tissues and its expression was significantly correlated with tumor size,
      intrahepatic metastases, portal venous invasion, and Barcelona Clinic Liver
      Cancer stage of disease in 2 cohorts of patients. On survival analysis, patients
      with high CKAP4 expression appeared to have a favorable overall survival and a
      longer disease-free survival compared with those with low expression. DHHC2
      expression was also examined in tissue microarray analysis by
      immunohistochemistry and the results demonstrated that 87.6% of the cases had low
      expression of DHHC2. Kaplan-Meier analysis indicated that a high level of DHHC2
      expression predicted favorable overall survival and disease-free survival rates
      in both the training cohort and validation set. Furthermore, the combination of
      CKAP4 and DHHC2 was found to have a more powerful efficiency in prognosis
      prediction than either one alone. CONCLUSIONS: To the best of our knowledge, the
      current study is the first to demonstrate that the expression of CKAP4 and its
      palmitoyl acyltransferase DHHC2 correlates with disease progression and
      metastasis in patients with HCC and may provide prognostic and therapeutic value.

PMID- 24863390
TI  - Causes of death in long-term survivors of head and neck cancer.
AB  - BACKGROUND: Survivors of head and neck squamous cell carcinoma (HNSCC) face
      excess mortality from multiple causes. METHODS: We used the population-based
      Surveillance, Epidemiology, and End Results (SEER) cancer registry data to
      evaluate the causes of death in patients with nonmetastatic HNSCC diagnosed
      between 1992 and 2005 who survived at least 3 years from diagnosis (long-term
      survivors). We used competing-risks proportional hazards regression to estimate
      probabilities of death from causes: HNSCC, second primary malignancy (SPM)
      excluding HNSCC, cardiovascular disease, and other causes. RESULTS: We identified
      35,958 three-year survivors of HNSCC with a median age at diagnosis of 60 years
      (range = 18-100 years) and a median follow-up of 7.7 years (range = 3-18 years).
      There were 13,120 deaths during the study period. Death from any cause at 5 and
      10 years was 15.4% (95% confidence interval [CI] = 15.0%-15.8%) and 41.0% (95% CI
      = 40.4%-41.6%), respectively. There were 3852 HNSCC deaths including both primary
      and subsequent head and neck tumors. The risk of death from HNSCC was greater in
      patients with nasopharynx or hypopharynx cancer and in patients with locally
      advanced disease. SPM was the leading cause of non-HNSCC death, and the most
      common sites of SPM death were lung (53%), esophagus (10%), and colorectal (5%)
      cancer. CONCLUSIONS: Many long-term HNSCC survivors die from cancers other than
      HNSCC and from noncancer causes. Routine follow-up care for HNSCC survivors
      should expand beyond surveillance for recurrent and new head and neck cancers.

PMID- 24863393
TI  - A vertically integrated solar-powered electrochromic window for energy efficient
      buildings.
AB  - A solution-processed self-powered polymer electrochromic/photovoltaic (EC/PV)
      device is realized by vertically integrating two transparent PV cells with an
      ECD. The EC/PV cell is a net energy positive dual functional device, which can be
      reversibly switched between transparent and colored states by PV cells for
      regulating incoming sunlight through windows. The two PV cells can individually,
      or in pairs, generate electricity. 

PMID- 24863392
TI  - Lack of reduction in racial disparities in cancer-specific mortality over a 20
      year period.
AB  - BACKGROUND: To the authors' knowledge, it remains unknown whether race-based
      differences in cancer outcomes have changed with time. In the current study, the
      authors assessed whether racial disparities in cancer-specific mortality have
      improved over the last 20 years. METHODS: The Surveillance, Epidemiology, and End
      Results program was used to identify 2,713,474 patients diagnosed between 1988
      and 2007 with either lung, breast, prostate, or colorectal cancer (the leading 3
      causes of cancer-related mortality among each sex). After exclusions, 1,001,978
      patients remained eligible for analysis. The impact of race on cancer-specific
      mortality was assessed using the regression model of Fine and Gray; an
      interaction model evaluated trends over time. RESULTS: African Americans
      presented with a more advanced stage of disease (P < .001) and underwent
      definitive therapy less often (P < .001) than whites. After adjustment for
      demographics and year of diagnosis, African Americans were found to have higher
      estimates of cancer-specific mortality than whites for all cancers combined
      (hazards ratio, 1.28; 95% confidence interval, 1.26-1.30 [P < .001]) and within
      each individual cancer (each P < .05). These differences did not change
      significantly between 1988 through 1997 and 1998 through 2007, except among
      patients with breast cancer, in whom survival disparities increased. These
      findings remained significant after adjustment for stage of disease at
      presentation and receipt of definitive therapy (hazards ratio for breast cancer
      mortality in African Americans vs whites: 1.37 from 1988-1997 and 1.53 from 1998
      2007; P for interaction, < .001). CONCLUSIONS: The survival gap for African
      Americans has not closed over time. Race-based differences in outcome persist
      independent of stage of disease and treatment, suggesting that additional
      strategies beyond screening and improving access to care, such as further
      research into tumor biologies disproportionately affecting African Americans, are
      needed to improve survival for African American patients with cancer.

PMID- 24863394
TI  - Competence in advanced older people nursing: development of 'nursing older people
      -competence evaluation tool'.
AB  - BACKGROUND: Community care is characterised by a move from institutionalised to
      home-based care, a large patient population with comorbidities including
      cognitive failure, and nurses who struggle to keep up with their many competence
      demands. No study has examined the competence of nurses based on present demands,
      and an instrument for this purpose is lacking. AIM AND OBJECTIVE: We conducted a
      Delphi study based in Norway to develop the substantial content of a new
      competence measurement instrument. We sought to reach consensus regarding which
      nursing staff competence is most relevant to meet the current needs of older
      patients. DESIGN AND METHOD: A total of 42 experts participated in three
      consecutive panel investigations. Snowball sampling was used. The experts were
      clinicians, leaders, teachers, researchers and relatives of older people who
      required nursing. In Round 1, all experts were interviewed individually. These
      data were analysed using meaning coding and categorisation. In Rounds 2 and 3,
      the data were collected using electronic questionnaires and analysed
      quantitatively with SPSS. RESULTS: The experts agreed that health promotion as
      well as disease prevention, treatment, palliative care, ethics and regulation,
      assessment and taking action, covering basic needs, communication and
      documentation, responsibility and activeness, cooperation, and attitudes towards
      older people were the most relevant categories of competence. CONCLUSIONS: The
      experts showed clear consensus regarding the most relevant and current competence
      for nurses of older people. Assuming that older people in need of health care
      have the same requirements across cultures, this study's findings could be used
      as a basis for international studies. IMPLICATIONS FOR PRACTICE: Those who nurse
      older people require competence that is complex and comprehensive. One way to
      evaluate nursing competence is through evaluation tools such as the Nursing Older
      People--Competence Evaluation tool.

PMID- 24863396
TI  - Female donors and donors who are lighter than their recipient are less likely to
      meet the CD34+ cell dose requested for peripheral blood stem cell
      transplantation.
AB  - BACKGROUND: It is of clinical relevance to recognize donors who are unlikely to
      meet the requested stem cell dose for transplantation, as this group may benefit
      from an alternative mobilization regimen. This study was performed to evaluate
      the frequency of unrelated donor peripheral blood stem cell (PBSC) collections
      that meet the target yield and the impact of donor factors on this. STUDY DESIGN
      AND METHODS: All sequential PBSC collections facilitated by the national registry
      (n = 323) from January through December 2011 were analyzed. Donor factors
      analyzed included age, sex, weight, and presence of a central line. RESULTS: In
      univariate analyses, we found that reaching the target yield was significantly
      associated with a higher donor weight (85.6 kg vs. 75.3 kg, p < 0.001), male
      donor sex (55% vs. 19%, p < 0.001), a positive difference in weight between donor
      and recipient (4.3 kg vs. -8 kg, p < 0.001), and a higher volume of blood
      processed (13.8 L vs. 11.9 L, p < 0.001). After stepwise binary logistic
      regression, sex (p < 0.001) and difference between donor and recipient weight (p
      < 0.005) remained significantly associated with target yield being met after 1
      day of collection. CONCLUSIONS: This study shows than women and donors who are
      lighter than their recipient have a decreased likelihood of meeting the
      transplant physician's requested dose. New strategies to improve mobilization in
      such donors are needed. These findings may also impact future donor recruitment
      strategies.

PMID- 24863395
TI  - Hypoglycin A concentrations in seeds of Acer pseudoplatanus trees growing on
      atypical myopathy-affected and control pastures.
AB  - BACKGROUND: Hypoglycin A, found in seeds of Acer negundo, appears to cause
      seasonal pasture myopathy (SPM) in North America and is implicated in atypical
      myopathy (AM) in Europe. Acer negundo is uncommon in Europe. Thus, the potential
      source of hypoglycin A in Europe is unknown. HYPOTHESIS AND OBJECTIVES: We
      hypothesized that seeds of Acer pseudoplatanus were the source of hypoglycin A in
      Europe. Our objective was to determine the concentration of hypoglycin A in seeds
      of A. pseudoplatanus trees located in pastures where previous cases of AM had
      occurred. ANIMALS: None. METHODS: University of Berne records were searched to
      retrospectively identify 6 farms with 10 AM cases and 11 suspected AM deaths
      between 2007 and 2011. During October 2012, A. pseudoplatanus seeds were
      collected from 2 to 6 trees per pasture on 6 AM farms (7 pastures) from trees in
      or close to 2 pastures on 2 control farms where AM had not been previously
      reported. Hypoglycin A in seeds was analyzed by GC-MS. RESULTS: Acer
      pseudoplatanus trees were identified on all AM pastures. Hypoglycin A was
      detected in all A. pseudoplatanus seeds in highly variable concentrations ranging
      from 0.04 to 2.81 MUg/mg (mean 0.69) on AM farms and 0.10 to 9.12 MUg/mg (mean
      1.59) on control farms. CONCLUSION AND CLINICAL IMPORTANCE: Preventing horses
      from grazing pastures containing A. pseudoplatanus seeds during late fall and
      early spring might be the best means to prevent AM.

PMID- 24863397
TI  - Functionalized polyglycerol amine nanogels as nanocarriers for DNA.
AB  - Polyglycerol based nanogels (nPG) can function as cellular delivery systems.
      These nPGs are synthesized with different amine densities (nPG amines) by acid
      catalyzed epoxide-opening polymerization using a mini-emulsion approach and
      surface modification. All the synthesized nanogels are characterized by NMR,
      dynamic light scattering, and zeta-potential, showing slightly positive surface
      charge and a homogeneous size of ~100 nm. The use of these systems for delivery
      applications is demonstrated with regard to polyplex formation, cytotoxicity, and
      cellular uptake studies. It is depicted that the CE50 value of the high loaded
      nPG amines is eight times higher than the low loaded ones. The influence of the
      amine loading percentage on the nanogel and the effects of polyvalency in these
      architecture is discussed. 

PMID- 24863398
TI  - Suppressive immune response of poly-(sarcosine) chains in peptide-nanosheets in
      contrast to polymeric micelles.
AB  - Nanoparticles are expected to be applicable for the theranostics as a carrier of
      the diagnostic and therapeutic agents. Lactosome is a polymeric micelle composed
      of amphiphilic polydepsipeptide, poly(sarcosine)64-block-poly(L-lactic acid)30,
      which was found to accumulate in solid tumors through the enhanced permeability
      and retention effect. However, lactosome was captured by liver on the second
      administration to a mouse. This phenomenon is called as the accelerated blood
      clearance phenomenon. On the other hand, peptide-nanosheet composed of
      amphiphilic polypeptide, poly(sarcosine)60-block-(L-Leu-Aib)6, where the poly(L
      lactic acid) block in lactosome was replaced with the (L-Leu-Aib)6 block,
      abolished the accelerated blood clearance phenomenon. The ELISA and in vivo near
      infrared fluorescence imaging revealed that peptide-nanosheets did not activate
      the immune system despite the same hydrophilic block being used. The high surface
      density of poly(sarcosine) chains on the peptide-nanosheet may be one of the
      causes of the suppressive immune response.

PMID- 24863399
TI  - Antigen-specific IgE in middle ear effusion of patients with eosinophilic otitis
      media.
AB  - BACKGROUND: Eosinophilic otitis media (EOM) is an intractable otitis media
      characterized by a highly viscous effusion that contains eosinophils. We
      previously reported that high levels of IgE were detected in middle ear effusion
      (MEE) of patients with EOM. OBJECTIVE: To examine antigen-specific IgE in MEE of
      patients with EOM to clarify the pathogenesis of EOM. METHODS: Twenty-six
      patients with EOM associated with bronchial asthma were included in this study.
      Antigen-specific IgE against inhalant and bacterial antigens were measured in the
      serum and MEE of these patients. RESULTS: In patients with EOM, 1 or more antigen
      specific IgEs were detected from the MEE of 16 of 26 patients (62%), whereas 1 of
      9 control patients (11%) had antigen-specific IgE (P < .01). Total serum IgE
      concentrations were not different between the groups who tested positive (16
      patients) and negative (10 patients) for antigen-specific IgE. None of the fungi
      specific IgEs were detected in serum even though 11 patients tested positive for
      1 or more fungal antigens detected in MEE. The severity score of EOM in the
      antigen-specific IgE-positive group was significantly higher than that in the
      antigen-specific IgE-negative group (P < .05). CONCLUSION: Antigen-specific IgE
      against inhalant and bacterial antigens may be locally produced in the middle ear
      mucosa in patients with EOM. In particular, local sensitization against fungi
      together with Staphylococcus aureus could result in local IgE production in the
      middle ear and may be responsible for the severity of EOM.

PMID- 24863400
TI  - Identification of a novel protein allergen in Mediterranean silverside fish
      species.

PMID- 24863402
TI  - Editorial commentary: how can understanding the phenotype of Pseudomonas
      aeruginosa lead to more successful eradication strategies in cystic fibrosis?

PMID- 24863401
TI  - Pseudomonas aeruginosa phenotypes associated with eradication failure in children
      with cystic fibrosis.
AB  - BACKGROUND: Pseudomonas aeruginosa is a key respiratory pathogen in people with
      cystic fibrosis (CF). Due to its association with lung disease progression,
      initial detection of P. aeruginosa in CF respiratory cultures usually results in
      antibiotic treatment with the goal of eradication. Pseudomonas aeruginosa
      exhibits many different phenotypes in vitro that could serve as useful prognostic
      markers, but the relative relationships between these phenotypes and failure to
      eradicate P. aeruginosa have not been well characterized. METHODS: We measured 22
      easily assayed in vitro phenotypes among the baseline P. aeruginosa isolates
      collected from 194 participants in the 18-month EPIC clinical trial, which
      assessed outcomes after antibiotic eradication therapy for newly identified P.
      aeruginosa. We then evaluated the associations between these baseline isolate
      phenotypes and subsequent outcomes during the trial, including failure to
      eradicate after antipseudomonal therapy, emergence of mucoidy, and occurrence of
      an exacerbation. RESULTS: Baseline P. aeruginosa isolates frequently exhibited
      phenotypes thought to represent chronic adaptation, including mucoidy. Wrinkly
      colony surface and irregular colony edges were both associated with increased
      risk of eradication failure (hazard ratios [95% confidence intervals], 1.99 [1.03
      3.83] and 2.14 [1.32-3.47], respectively). Phenotypes reflecting defective quorum
      sensing were significantly associated with subsequent mucoidy, but no phenotype
      was significantly associated with subsequent exacerbations during the trial.
      CONCLUSIONS: Pseudomonas aeruginosa phenotypes commonly considered to reflect
      chronic adaptation were observed frequently among isolates at early detection. We
      found that 2 easily assayed colony phenotypes were associated with failure to
      eradicate after antipseudomonal therapy, both of which have been previously
      associated with altered biofilm formation and defective quorum sensing.

PMID- 24863403
TI  - Demographic analysis of open and arthroscopic distal clavicle excision in a
      private insurance database.
AB  - PURPOSE: The purpose of this study was to evaluate and quantify the demographic
      characteristics of patients undergoing open and arthroscopic distal clavicle
      excision (DCE) in the United States while also describing changes in practice
      patterns over time. METHODS: Patients who underwent DCE from 2004 to 2009 were
      identified by Current Procedural Terminology (CPT) codes in a national database
      of orthopaedic insurance records. The year of procedure, age, sex, geographic
      region, and concomitant rotator cuff repair or subacromial decompression (SAD)
      were recorded for each patient. Results were reported as the incidence of
      procedures identified per 10,000 patients searched in the database. RESULTS:
      Between 2004 and 2009, 73,231 DCEs were performed; 74% were arthroscopic and 26%
      were open. The incidence of arthroscopic DCE increased from 37.8 in 2004 to 58.5
      in 2009 (P < .001), whereas the incidence of open DCE decreased from 21.1 in 2004
      to 14.1 in 2009 (P < .001). Sixty-one percent of DCEs were performed in men (P <
      .001). Women were more likely to undergo an arthroscopic procedure (P < .001).
      Arthroscopic DCE was most common in patients aged 50 to 59 years (P < .001). Open
      DCE was most common in patients aged 60 to 69 years (P < .001). Open rotator cuff
      repair and SAD were concomitantly performed in 38% and 23% of open DCEs,
      respectively. Arthroscopic rotator cuff repair and SAD were concomitantly
      performed in 33% and 95% arthroscopic DCEs, respectively. CONCLUSIONS: This
      analysis of DCE using a private insurance database shows that arthroscopic DCEs
      progressively increased, whereas open DCEs concomitantly decreased between 2004
      and 2009. The majority of DCEs were performed in men between the ages of 50 and
      59 years. Both arthroscopic and open DCEs are frequently performed in conjunction
      with rotator cuff repair or SAD. LEVEL OF EVIDENCE: Level IV, cross-sectional
      study.

PMID- 24863405
TI  - C-reactive protein and erythrocyte sedimentation rate changes after arthroscopic
      anterior cruciate ligament reconstruction: guideline to diagnose and monitor
      postoperative infection.
AB  - PURPOSE: The purposes of our study were to determine normative C-reactive protein
      (CRP) and erythrocyte sedimentation rate (ESR) values from a retrospective review
      of patients with and without infection after anterior cruciate ligament (ACL)
      reconstruction and to determine CRP and ESR threshold levels that can serve as
      diagnostic indicators of infection. We also tried to draw a curve of CRP and ESR
      value changes after treatment of ACL infection to evaluate the response to
      treatment of the infection. METHODS: A retrospective chart review was performed
      of arthroscopic ACL reconstruction patients from 2007 to 2008 (noninfection
      group) and all patients with postoperative intra-articular infection from 1997 to
      2010 (infection group). We collected the CRP and ESR values on the third and
      fifth postoperative days in the noninfection group and before infection treatment
      and on the first, third, fifth, seventh, 10th, 14th, 21st, 28th, and 35th days
      after infection treatment in the infection group. Sensitivity, specificity, and
      Youden's index were calculated for different threshold values of CRP and ESR as
      predictors of infection. Receiver operator curves were obtained for CRP and ESR
      on the fifth postoperative day. RESULTS: Of 122 patients, 83 had normal joints
      and 39 had septic joints. The mean CRP and ESR values in patients with septic
      joints were 101.9 mg/L and 57.1 mm/h, respectively, which were significantly
      higher than those in the noninfection group (P < .01). A CRP value of 41 mg/L and
      ESR value of 32 mm/h were the optimal thresholds to predict an infection, which
      had the highest Youden's index of all calculated values and had sensitivity
      values of 94.1% and 91.2%, respectively, and specificity values of 97.6% and
      80.5%, respectively. The peak CRP level after infection treatment occurred
      earlier than the peak ESR level (first day v third day) and returned to normal
      more quickly (21st day v 28th day). CONCLUSIONS: Both CRP and ESR were helpful in
      determining the presence of a normal or septic joint. The threshold values of 41
      mg/L for CRP and 32 mm/h for ESR had the most optimal sensitivity and
      specificity. The peak CRP level occurred earlier than the peak ESR level after
      treatment of postoperative infection and returned to normal more quickly. In this
      study CRP was more useful than ESR to evaluate the response of infection to
      treatment. LEVEL OF EVIDENCE: Level IV, diagnostic study.

PMID- 24863404
TI  - Rotator cuff tear degeneration and cell apoptosis in smokers versus nonsmokers.
AB  - PURPOSE: The purpose of this study was to assess the effect of smoking on
      supraspinatus tendon degeneration, including cellular alterations, proliferation,
      and apoptosis of tendon cells. METHODS: Supraspinatus tendon samples of 10
      smokers and 15 nonsmokers with full-thickness tears were compared, focusing on
      the severity of tendon histopathology including apoptosis (programmed cell
      death), cellularity, and proliferation. Immunohistochemistry was used to assess
      the density of apoptotic cells and proliferation. The extent of tendon
      degeneration was classified according to a revised version of the Bonar tendon
      histopathology score. RESULTS: The smokers were younger (P = .01). The symptom
      duration among smokers was longer (P < .05). The supraspinatus tendons from the
      smokers presented significantly more advanced degenerative changes (Bonar score,
      13.5 [interquartile range, 1.4] v 9 [interquartile range, 3]; P < .001). The
      smokers' tendons showed increased density of apoptotic cells (0.108 [SE, 0.038] v
      0.0107 [SE, 0.007]; P = .024) accompanied by reduced tenocyte density (P = .019)
      and upregulation of proliferative activity (P < .0001). CONCLUSIONS: Smoking is
      associated with worsened supraspinatus tendon histopathology and increased
      apoptosis. CLINICAL RELEVANCE: Pronounced degenerative changes, reduced tendon
      cellularity, and increased apoptosis may indicate reduced tendon healing capacity
      in smokers.

PMID- 24863406
TI  - Sleep duration and abnormal serum lipids: the China Health and Nutrition Survey.
AB  - OBJECTIVE: To examine the associations between sleep duration and total
      cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C),
      high density lipoprotein cholesterol (HDL-C), apolipoprotein B (ApoB),
      apolipoprotein A1 (ApoA1), and lipoprotein (a) [Lp(a)]. METHODS: The present
      study analyzed 8574 adults from the China Health and Nutrition Survey (2009).
      Sleep duration was classified into < or = 6, 7, 8, 9, and > or = 10 h. Age,
      education, occupation, current smoking, current drinking, physical activity, body
      mass index, hypertension, and diabetes were adjusted as confounders in gender
      stratified multiple logistic regression models. RESULTS: Compared with women
      reporting 8h sleep duration, the odds ratios (ORs) and 95% confidence intervals
      (CIs) of high TC for those with < or = 6, 7, 9, and > or = 10 h were 1.65 (1.32
      2.06), 1.19 (1.00-1.43), 1.11 (0.89-1.39), and 1.27 (1.02-1.60) after adjusting
      for confounders. Likewise, the ORs (95% CIs) of high LDL-C were 1.71 (1.28-2.29),
      1.36 (1.05-1.76), 1.04 (0.74-1.46), and 1.09 (0.78-1.53), whereas those of high
      ApoB were 1.80 (1.34-2.42), 1.15 (0.88-1.52), 0.95 (0.66-1.35), and 1.00 (0.70
      1.43) for women with < or = 6, 7, 9, and > or = 10 h sleep duration,
      respectively. These associations were not statistically significant in men.
      CONCLUSIONS: Both shorter and longer sleep durations were associated with higher
      risks of abnormal serum lipid profiles in women but not in men.

PMID- 24863407
TI  - Prescription of opioid and nonopioid analgesics for dental care in emergency
      departments: Findings from the National Hospital Ambulatory Medical Care Survey.
AB  - OBJECTIVES: The aim of this study was to examine trends and associated factors in
      the prescription of opioid analgesics, nonopioid analgesics, opioid and nonopioid
      analgesic combinations, and no analgesics by emergency physicians for
      nontraumatic dental condition (NTDC)-related visits. Our secondary aim was to
      investigate whether race/ethnicity is a possible predictor of receiving a
      prescription for either type of medication for NTDC visits in emergency
      departments (EDs) after adjustment for potential covariates. METHODS: We analyzed
      data from the National Hospital Ambulatory Medical Care Survey for 1997-2000 and
      2003-2007, and used multinomial multivariate logistic regression to estimate the
      probability of receiving a prescription for opioid analgesics, nonopioid
      analgesics, or a combination of both, compared with receiving no analgesics for
      NTDC-related visits. RESULTS: During 1997-2000 and 2003-2007, prescription of
      opioid analgesics and combinations of opioid and nonopioid analgesics increased,
      and that of no analgesics decreased over time. The prescription rates for opioid
      analgesics, nonopioid analgesics, opioid and nonopioid analgesic combinations,
      and no analgesics for NTDC-related visits in EDs were 43 percent, 20 percent, 12
      percent, and 25 percent, respectively. Majority of patients categorized as having
      severe pain received prescriptions for opioids for NTDC-related visits in EDs.
      After adjusting for covariates, patients with self-reported dental reasons for
      visit and severe pain had a significantly higher probability of receiving
      prescriptions for opioid analgesics and opioid and nonopioid analgesic
      combinations. CONCLUSIONS: Prescription of opioid analgesics increased over time.
      ED physicians were more likely to prescribe opioid analgesics and opioid and
      nonopioid analgesic combinations for NTDC-related visits with reported severe
      pain.

PMID- 24863408
TI  - Enhanced transglutaminase 2 expression in response to stress-related
      catecholamines in macrophages.
AB  - Transglutaminase 2 (TG2) is a multifunctional protein that contributes to
      inflammatory disease when aberrantly expressed. Although macrophages express TG2,
      the factor stimulating TG2 expression remains poorly characterized in these
      cells. In the present study, we examined the effects of the stress-related
      catecholamines adrenaline and noradrenaline on macrophage expression of TG2 in
      RAW264.7 murine macrophages and murine bone marrow-derived macrophages. Treatment
      with adrenaline markedly increased TG2 mRNA expression and increased TG2 protein
      levels. While the beta2-adrenoceptor-selective antagonist ICI 118,551 completely
      blocked adrenaline-induced TG2 mRNA expression, the beta2-adrenoceptor specific
      agonist salmeterol increased TG2 expression. Noradrenaline also increased TG2
      mRNA expression at higher doses than the effective doses of adrenaline. The
      effect of adrenaline on TG2 mRNA expression was mimicked by treatment with the
      membrane-permeable cAMP analog 8-Br-cAMP. Thus, increased intracellular cAMP
      following stimulation of beta2-adrenoceptors appeared to be responsible for
      adrenaline-induced TG2 expression. Because stress events activate the sympathetic
      nervous system and result in secretion of the catecholamines, adrenoceptor
      mediated increase in macrophage TG2 expression might be associated with stress
      related inflammatory disorders.

PMID- 24863409
TI  - Yeast cell surface display of linoleic acid isomerase from Propionibacterium
      acnes and its application for the production of trans-10, cis-12 conjugated
      linoleic acid.
AB  - Conjugated linoleic acid (CLA), a family of geometric and positional isomers of
      linoleic acid, has many health-promoting properties. Different isomers of CLA may
      have very different physiological effects. In the current work, we explore the
      possibility to produce single isomer of CLA by using biocatalysis based on
      displayed biocatalysts on the yeast cell surfaces. A reporter system used to
      assess gene expression and protein distribution was established by combining the
      egfp gene to the N-terminus of Propionibacterium acnes pai gene encoding the
      linoleic isomerase onto vector pYD1. After induction of the yeast strains
      containing pYD1::egfp::pai with galactose, strong green fluorescence was observed
      on the surface of cells, demonstrating that the fusion protein was successfully
      displayed. Using the engineered strains as whole-cell biocatalyst, trans-10, cis
      12 CLA was detected in the reaction mixture. To improve the biocatalytic
      potential of this system, the first 20 amino codons of pai were modified, and the
      catalytic reaction conditions were optimized. Optimization of the codon usage
      resulted in 35% increase of CLA production, and the maximum yield of CLA was
      observed within 20 H in the optimal conditions: pH 7.0, 4 mg/mL linoleic acid, 37
      degrees C. The system established in the present work can guide the development
      of biocatalytic strategies to produce trans-10, cis-12 CLA single isomer. 

PMID- 24863411
TI  - Insecticide resistance and cross-resistance development in Colorado potato beetle
      Leptinotarsa decemlineata Say (Coleoptera: Chrysomelidae) populations in Canada
      2008-2011.
AB  - BACKGROUND: A survey of insecticide resistance in over 150 Canadian populations
      of Colorado potato beetle was completed between 2008 and 2011. Three
      neonicotinoid and two anthranilic diamide insecticides were tested at a
      discriminating concentration (DC) with second-instar larvae in a leaf-disc
      bioassay. RESULTS: The mean mortality for the imidacloprid (Admire) DC was 46-67%
      between 2008 and 2011 respectively. Over the 4 years, 10-46% and 26-40% of the
      populations were classified as resistant or showed reduced susceptibility to
      imidacloprid. The mean mortality for thiamethoxam (Actara) and clothianidin
      (Poncho/Titan) ranged from 56-76% in 2008 to 81-84% in 2010 for each insecticide
      respectively, indicating continuous susceptibility to clothianidin but reduced
      susceptibility to thiamethoxam. In 2008 and 2009, susceptibility to
      chlorantraniliprole (Coragen) was observed in 85% of populations. Similarly,
      cyantraniliprole (Cyazypyr) affected 93% of the 2009 and 74% of the 2010
      populations. There was a significant (P < 0.05) and high positive correlation (R
      = 0.4-0.84) between the three neonicotinoids, indicating the potential for cross
      resistance. CONCLUSIONS: The trend observed in decreasing susceptibility for
      thiamethoxam and clothianidin will continue unless resistance management
      practices are followed.

PMID- 24863410
TI  - Melatonin improves ultraviolet B-induced oxidative damage and inflammatory
      conditions in cutaneous tissue of a diurnal Indian palm squirrel Funambulus
      pennanti.
AB  - BACKGROUND: Skin is exposed to various abiotic and biotic factors. Solar
      radiation, of which ultraviolet (UV) rays are a principle component, increases
      the free radical load, and the accumulation of reactive oxygen species (ROS)
      causes lipid peroxidation, DNA damage and apoptosis, and is also associated with
      inflammatory responses recruiting molecules [nuclear factor (NF)-kappaB,
      interleukin (IL)-6] that can potentially further aggravate the damaged milieu of
      the cells. One of the potent causes of skin cancers is exposure to UV rays. UV
      radiation generates a wide range of biological responses such as adaptive,
      inflammatory and immunological reactions in the skin. OBJECTIVE: To examine the
      effects of pretreatment with melatonin on UVB (290-320 nm) radiation-mediated
      damage to the skin of a diurnal rodent Funambulus pennanti. RESULTS: The UVB
      radiation (1.5 J cm(-2) for 30 min daily on the shaved abdominal area) for 4 days
      caused a significant increase in the lipid peroxidation products (thiobarbituric
      acid reactive substances, TBARS) and decreased the activity of the antioxidant
      enzymes (superoxide dismutase, catalase and glutathione peroxidase) of the skin.
      Pretreatment with melatonin (100 MUg 100 g(-1) bodyweight subcutaneously)
      improved the damage induced by UVB radiation on the skin and might act via a
      receptor-independent mechanism. No significant effect of melatonin pretreatment
      was found on the expression pattern of MT1 (melatonin membrane receptor) and
      RORalpha (nuclear retinoic orphan receptor alpha), which suggests a receptor
      independent action. However, NF-kappaB and inflammatory cytokine IL-6 levels were
      downregulated in the squirrels pretreated with melatonin before the UVB
      radiation. CONCLUSION: UVB radiation induced oxidative stress in the skin
      culminating in an inflammatory response. The action of melatonin in protecting
      the skin from oxidative damage occurs in a receptor-independent manner by
      lowering the oxidative damage and inflammatory response. On the other hand,
      melatonin decreased the expression of NF-kappaB and the circulating
      proinflammatory cytokine IL-6, suggesting an anti-inflammatory action in
      protecting the skin from UVB radiation.

PMID- 24863412
TI  - The lateral line system in anuran tadpoles: neuromast morphology, arrangement,
      and innervation.
AB  - Anuran larvae have been classified into four morphological types which reflect
      intraordinal macroevolution. At present, complete characterizations of the
      lateral line system are only available for Xenopus laevis (Type I) and
      Discoglossus pictus (Type III). We analyzed the morphology, arrangement, and
      innervation of neuromasts related to the anterodorsal and anteroventral lateral
      line nerves in 10 anuran species representing Types I, II, and IV with the aim of
      interpreting the existing variation and discussing the evolution of the lateral
      line in anuran larvae. We found: (1) the presence of two orbital and three
      mandibular neuromast lines in all anuran larvae studied, (2) the ventral
      arrangement of mandibular neuromast lines appears to have evolved convergently in
      Larval Types I and II, and the lateroventral arrangement of mandibular lines of
      neuromasts appears to have evolved in Larval Types III and IV; (3) interspecific
      variation in the organization, size, and number of sensory cells per neuromast
      within the lines; and (4) the supralabial extension of the Angular line in
      Lepidobatrachus spp. and the tentacular location of the Oral neuromasts in X.
      laevis are concomitant with their particular morphologies. Based on the variation
      described we find that the lateral line system in anuran larvae seems to have
      been maintained without significant changes, with the exception of
      Lepidobatrachus spp. and Xenopus. These unique features added to other of
      Lepidobatrachus tadpoles are sufficient to propose a new Larval Type (V).

PMID- 24863413
TI  - Elaidic acid (EA) generates dysfunctional high-density lipoproteins and
      consumption of EA exacerbates hyperlipidemia and fatty liver change in zebrafish.
AB  - SCOPE: It is well known that trans-fatty acids have proatherogenic properties
      while HDL has antiatherogenic activities in plasma. However, there has been no
      report on the effects of trans-fat on the functional and structural properties of
      HDL. METHODS AND RESULTS: To compare physiological properties, we synthesized
      reconstituted HDL (rHDL) containing stearic acid (18:0), oleic acid (18:1, cis),
      or elaidic acid (EA, 18:1, trans). An rHDL containing EA (EA-rHDL) showed loss of
      antioxidant ability and induced the highest uptake of oxidized LDL into human
      macrophages. EA-rHDL caused the strongest cellular senescence in human dermal
      fibroblast cells along with the highest production of inflammatory species in
      macrophages co-treated with fructose. Injection of EA-rHDL into zebrafish embryos
      resulted in acute embryonic toxicity with the lowest survivability. Consumption
      of trans-fat for 20 weeks resulted in remarkable hyperlipidemia, elevation of
      serum cholesteryl ester transfer protein activity, hepatic inflammation, and
      fatty liver changes. CONCLUSION: Incorporation of EA impaired the beneficial
      effects of rHDL against atherogenesis. In zebrafish, EA-rHDL resulted in acute
      embryonic toxicity, and consumption of EA caused remarkable hyperlipidemia,
      inflammation, and fatty liver changes.

PMID- 24863414
TI  - Acute application of antioxidants protects against hyperoxia-induced reduction of
      plasma nitrite concentration.
AB  - We investigated the effects of acute intake of antioxidants on hyperoxia-induced
      oxidative stress, reduction of plasma nitrite and change in arterial stiffness.
      Twelve healthy males randomly consumed either placebo or an oral antioxidant
      cocktail (vitamin C, 1000 mg; vitamin E, 600 IU; alpha-lipoic acid, 600 mg).
      Every therapy was consumed once, a week apart, in a cross-over design, 30 min
      before the experiment. The volunteers breathed 100% normobaric oxygen between
      30th and 60th min of 1-h study protocol. Plasma levels of nitrite, lipid
      peroxides (LOOH) and vitamin C, arterial stiffness (indicated by augmentation
      index, AIx) and arterial oxygen (Ptc O2 ) pressure were measured before and after
      hyperoxia. Exposure to oxygen caused a similar increase of Ptc O2 in both placebo
      and antioxidants groups, confirming comparable exposure to hyperoxia (438 +/- 100
      versus 455 +/- 83 mm Hg). Vitamin C was increased in the antioxidants group
      confirming successful application of antioxidants (69 +/- 14 versus 57 +/- 15
      MUm). Hyperoxia resulted in increased AIx and LOOH and decreased nitrite in
      placebo (-32 +/- 11 versus -47 +/- 13%, 72 +/- 7 versus 62 +/- 6 MUm H2 O2 and
      758 +/- 184 versus 920 +/- 191 nm, respectively), but not in the antioxidants
      group (-42 +/- 13 versus -50 +/- 13%, 64 +/- 9 versus 61 +/- 8 MUm H2 O2 and 847
      +/- 156 versus 936 +/- 201 nm, respectively). The acute intake of selected
      antioxidants was effective in preserving bioavailabity of NO and vascular
      function, against hyperoxia-induced oxidative stress.

PMID- 24863415
TI  - The effects of river run-off on water clarity across the central Great Barrier
      Reef.
AB  - Changes in water clarity across the shallow continental shelf of the central
      Great Barrier Reef were investigated from ten years of daily river load,
      oceanographic and MODIS-Aqua data. Mean photic depth (i.e., the depth of 10% of
      surface irradiance) was related to river loads after statistical removal of wave
      and tidal effects. Across the ~25,000 km(2) area, photic depth was strongly
      related to river freshwater and phosphorus loads (R(2)=0.65 and 0.51,
      respectively). In the six wetter years, photic depth was reduced by 19.8% and
      below water quality guidelines for 156 days, compared to 9 days in the drier
      years. After onset of the seasonal river floods, photic depth was reduced for on
      average 6-8 months, gradually returning to clearer baseline values. Relationships
      were strongest inshore and midshelf (~12-80 km from the coast), and weaker near
      the chronically turbid coast. The data show that reductions in river loads would
      measurably improve shelf water clarity, with significant ecosystem health
      benefits.

PMID- 24863417
TI  - Extraordinary transformations to achieve the synthesis of remarkable aromatic
      compounds.

PMID- 24863416
TI  - Seasonal distribution of ultraphytoplankton and heterotrophic prokaryotes in
      relation to abiotic variables on the north coast of Sfax after restoration.
AB  - The Taparura project was set up to restore the north Sfax coast (Tunisia) by
      shutting down the northern phosphate plant responsible for chronic pollution and
      uncontrolled phosphogypsum dumping. The restoration effect on coastal
      ultraphytoplankton (<10 MUm) and heterotrophic prokaryotes was investigated using
      conventional flow cytometry over four successive seasons during 2009-2010. Cell
      concentrations were generally higher than values reported for the open sea, both
      in the western and eastern Mediterranean basins. One striking point was that chl
      a concentration on the north Sfax coast was unchanged after restoration but was
      still one order of magnitude higher than in the Gulf of Gabes. Restoration of pH,
      following the shutdown of the phosphate processing plants on the north coast,
      appeared to reach normal levels for seawater during the study, whereas seawater
      acidification persisted on the south coast where plants are still in operation.
      The largest ultraphytoplankton biomass was from an unknown cell group, whose
      identity and role needs to be established.

PMID- 24863418
TI  - Prevalence and demographic factors associated with vitamin A deficiency in
      Colombian children aged 12-59 months.
AB  - OBJECTIVE: To examine the sociodemographic factors associated with subclinical
      vitamin A deficiency in a representative sample of Colombian children. Subjects
      and methods A cross-sectional, descriptive study was conducted of data from the
      2010 National Nutrition Survey of Colombia (ENSIN 2010) on 4,279 children aged 12
      to 59 months. Plasma vitamin A levels were measured using high resolution liquid
      chromatography (HRLC), and sociodemographic factors (sex, age, ethnicity, SISBEN
      score, and geographic region) were collected using a structured survey.
      Prevalence rates and associations were established using a multivariate
      regression model. RESULTS: Vitamin A levels ranged from 7.5-93.7 MUg/dL
      (mean=26.2; 95% CI, 25.9 to 26.5MUg/dL). Vitamin A levels less than 20 MUg/dL
      (subclinical deficiency) were found in 24.3% of children. Children belonging to
      ethnic groups of African ascent, those living in the Orinoquia and Amazonia
      regions, and those aged 12-23 months had the greatest subclinical vitamin A
      deficiencies (29.5%, 31.1%, and 27.6% respectively. Regression models showed that
      age ranging from 12 and 23 months (OR 1.32; 95% CI, 1.01 to 1.73), a SISBEN score
      1 (OR 1.66; 95% CI, 1.18 to 2.34), an African ascent (OR 1.35; 95% CI, 1.05 to
      1.74), and living in the Orinoquia and Amazonia regions (OR 2.38; 95% CI, 1.62 to
      3.51) were factors associated to subclinical vitamin A deficiency. CONCLUSIONS:
      The study population shows a high prevalence of subclinical vitamin A deficiency,
      and comprehensive interventions involving nutritional and educational components
      are therefore recommended.

PMID- 24863419
TI  - Functional and anatomical brain deficits in drug-naive major depressive disorder.
AB  - BACKGROUND: Functional and anatomical deficits have been involved in the
      neurobiology of major depressive disorder (MDD). However, no study has ever been
      conducted to examine whether and how functional alterations are related to
      anatomical deficits in MDD. This study aimed to determine the association between
      brain functional and anatomical deficits in drug-naive MDD. METHODS: Forty-four
      patients with MDD and 44 age-, sex-, and education-matched healthy controls
      underwent structural and resting-state functional magnetic resonance imaging
      scanning. The voxel-based morphometry (VBM) and amplitude of low-frequency
      fluctuation (ALFF) methods were used to analyze the imaging data. RESULTS: VBM
      analysis showed gray matter volume (GMV) reductions in the parietal-temporal
      regions (i.e., the right inferior temporal gyrus and the left angular gyrus).
      Functional alterations revealed by ALFF mainly occurred in the temporal regions
      (i.e., the left middle temporal gyrus and the right superior temporal gyrus) and
      the cerebellum (i.e., the culmen). There is no overlap between brain regions with
      functional alterations and anatomical deficits in the patients and their
      subgroups (first-episode depression and recurrent depression). The episode number
      and the illness duration were correlated with the mean GMV values of the left
      angular gyrus. CONCLUSIONS: A dissociation pattern of brain functional and
      anatomical deficits is observed in MDD. Our findings suggest that brain
      functional and anatomical deficits contribute independently to the neurobiology
      of MDD.

PMID- 24863421
TI  - Evaluation of a multiplex PCR to identify and serotype Actinobacillus
      pleuropneumoniae serovars 1, 5, 7, 12 and 15.
AB  - The aim of this study was to validate a multiplex PCR for the species
      identification and serotyping of Actinobacillus pleuropneumoniae serovars 1, 5,
      7, 12 and 15. All 15 reference strains and 411 field isolates (394 from
      Australia, 11 from Indonesia, five from Mexico and one from New Zealand) of A.
      pleuropneumoniae were tested with the multiplex PCR. The specificity of this
      multiplex PCR was validated on 26 non-A. pleuropneumoniae species. The multiplex
      PCR gave the expected results with all 15 serovar reference strains and agreed
      with conventional serotyping for all field isolates from serovars 1 (n = 46), 5
      (n = 81), 7 (n = 80), 12 (n = 16) and serovar 15 (n = 117). In addition, a
      species-specific product was amplified in the multiplex PCR with all 411 A.
      pleuropneumoniae field isolates. Of 25 nontypeable field isolates only two did
      not yield a serovar-specific band in the multiplex PCR. This multiplex PCR for
      serovars 1, 5, 7, 12 and 15 is species specific and capable of serotyping
      isolates from diverse locations. Significance and impact of the study: A
      multiplex PCR that can recognize serovars 1, 5, 7, 12 and 15 of A.
      pleuropneumoniae was developed and validated. This novel diagnostic tool will
      enable frontline laboratories to provide key information (the serovar) to guide
      targeted prevention and control programmes for porcine pleuropneumonia, a serious
      economic disease of pigs. The previous technology, traditional serotyping, is
      typically provided by specialized reference laboratories, limiting the capacity
      to respond to this key disease.

PMID- 24863420
TI  - Interplay among Pseudomonas syringae HrpR, HrpS and HrpV proteins for regulation
      of the type III secretion system.
AB  - Pseudomonas syringae pv. tomato DC3000, a plant pathogenic gram-negative
      bacterium, employs the type III secretion system (T3SS) to cause disease in
      tomato and Arabidopsis and to induce the hypersensitive response in nonhost
      plants. The expression of T3SS is regulated by the HrpL extracytoplasmic sigma
      factor. Expression of HrpL is controlled by transcriptional activators HrpR and
      HrpS and negative regulator HrpV. In this study, we analysed the organization of
      HrpRS and HrpV regulatory proteins and interplay between them. We identified one
      key residue I26 in HrpS required for repression by HrpV. Substitution of I26 in
      HrpS abolishes its interaction with HrpV and impairs interactions between HrpS
      and HrpR and the self-association of HrpS. We show that HrpS self-associates and
      can associate simultaneously with HrpR and HrpV. We now propose that HrpS has a
      central role in the assembly of the regulatory HrpRSV complex. Deletion analysis
      of HrpR and HrpS proteins showed that C-terminal parts of HrpR and HrpS confer
      determinants indispensable for their self-assembly. 

PMID- 24863423
TI  - The biosynthesis and catabolism of the maleic anhydride moiety of stipitatonic
      acid.
AB  - A series of directed knockout experiments, combined with an in vitro assay of
      pathway components, has elucidated for the first time the chemical steps involved
      in the biosynthesis of the tropolone class of fungal maleic anhydrides. The
      pathway involves the stepwise oxidation of aldehyde and methyl carbon atoms to
      form a 1,2-dicarboxylate. A hydrolase-catalyzed interconversion of this and the
      corresponding maleic anhydride, followed by decarboxylation of the diacid leads
      to the pathway's final product of stipitatic acid. 

PMID- 24863422
TI  - Virtual Electrode Recording Tool for EXtracellular potentials (VERTEX): comparing
      multi-electrode recordings from simulated and biological mammalian cortical
      tissue.
AB  - Local field potentials (LFPs) sampled with extracellular electrodes are
      frequently used as a measure of population neuronal activity. However, relating
      such measurements to underlying neuronal behaviour and connectivity is non
      trivial. To help study this link, we developed the Virtual Electrode Recording
      Tool for EXtracellular potentials (VERTEX). We first identified a reduced neuron
      model that retained the spatial and frequency filtering characteristics of
      extracellular potentials from neocortical neurons. We then developed VERTEX as an
      easy-to-use Matlab tool for simulating LFPs from large populations (>100,000
      neurons). A VERTEX-based simulation successfully reproduced features of the LFPs
      from an in vitro multi-electrode array recording of macaque neocortical tissue.
      Our model, with virtual electrodes placed anywhere in 3D, allows direct
      comparisons with the in vitro recording setup. We envisage that VERTEX will
      stimulate experimentalists, clinicians, and computational neuroscientists to use
      models to understand the mechanisms underlying measured brain dynamics in health
      and disease. 

PMID- 24863425
TI  - Proarrhythmic effect of "reverse mode switch" in a patient with long-QT syndrome.

PMID- 24863426
TI  - Outcomes of testosterone therapy in men with testosterone deficiency (TD): part
      II.
AB  - Testosterone (T) deficiency (TD) is a common clinical condition, which
      contributes to co-morbidities including loss of muscle mass, increased fat mass,
      increased inflammation, insulin resistance, risk of vascular disease, sexual
      dysfunction, fatigue, depressed mood and reduced quality of life. T therapy
      attenuates inflammation, increases insulin sensitivity, muscle mass and reduces
      fat mass and adiposity. T therapy improves lipid profiles and endothelial
      function and reduces systolic and diastolic blood pressure. In addition, T
      therapy may reduce risk of vascular disease and mortality. T therapy improves
      bone mineral density and increases energy and vitality and improves mood and
      sexual function and overall quality of life. T therapy appears to be safe if
      treatment and monitoring are appropriately executed. The evidence available to
      date does not support alleged concerns regarding risk of cardiovascular disease
      and prostate cancer. Indeed, T therapy remains controversial. The data in the
      contemporary literature suggest that T therapy reduces cardiovascular risk and
      fears promoted by some recent studies should be re-evaluated. The cardiovascular
      risk and mortality with T therapy must await large prospective controlled
      clinical trials, which depend on many complex factors. Such studies may be
      prohibitive in the current environment due to logistical challenges, such as
      recruiting large number of men to be treated for long-durations with appropriate
      follow-up, requiring astronomical cost. 

PMID- 24863424
TI  - Nasal and systemic inflammatory profile after short term smoking cessation.
AB  - INTRODUCTION: Smoking cessation promotes health benefits and, despite cigarette
      smoking be an important pro inflammatory stimulus, there are few studies
      concerning the nasal and systemic inflammation; as well as the mucociliary
      clearance behavior in smokers after short period of smoking cessation. AIM: To
      evaluate the nasal and systemic inflammatory markers and mucociliary clearance
      behavior after 30 days of cigarette smoking abstinence. METHODS: Twenty-five
      smokers were included and divided into two groups: abstinent smokers (n = 14) and
      current smokers (n = 11). Tumor necrosis factor alpha (TNF-alpha), interleukin
      (IL)-6, IL-8 and IL-10 were measured on nasal lavage and blood serum samples by
      ELISA at baseline and after 30 days. The mucociliary clearance, exhaled carbon
      monoxide (exCO) and carboxyhemoglobin (HbCO) were also measured at the same
      moments. RESULTS: There was a decrease of TNF-alpha level only in blood serum at
      30 days of abstinence compared to current smokers. The mucociliary clearance
      improved and there was a reduction in exCO and HbCO (p < 0.05 for all) after 30
      days of smoking cessation. CONCLUSION: The short term smoking abstinence
      decreased systemic inflammation and improved nasal mucociliary clearance, despite
      not having changed the nasal inflammation.

PMID- 24863427
TI  - Systemic lupus erythematosus and transient left ventricular noncompaction.
AB  - OBJECTIVES: Myocarditis is a rare but serious manifestation of patients with
      systemic lupus erythematosus (SLE). Left ventricular noncompaction (LVNC) is a
      disorder of myocardial morphogenesis frequently associated to neuromuscular
      diseases. Hypertrabeculation, a cardinal echocardiographic feature of LVNC, might
      represent a morphological expression of a number of morbidities, nevertheless.
      The relationship of LVNC with connective tissue disorders such as SLE is unknown.
      We aim to present a case of a patient with SLE who recently showed features
      compatible with an atypical LVNC. METHODS: To report a case of a young female
      with a 10-year history of SLE who developed haematological disease activity and
      cardiac failure. RESULTS: Ecocardiography showed
      hypertrabeculation/noncompaction, a very low ejection fraction and pulmonary
      hypertension. Clinical and echocardiographic features reverted with standard
      treatment for SLE activity and cardiac insufficiency. CONCLUSION: The transitory
      aspect of the cardiomyopathy made unlikely a "true" LVNC for this patient, but
      she might have presented a lupus myocarditis with "LVNC-like" features. The
      occurrence of hypertrabeculated myocardium in patients with SLE warrants further
      studies.

PMID- 24863428
TI  - Activation of lymphocyte autophagy/apoptosis reflects haemodynamic inefficiency
      and functional aerobic impairment in patients with heart failure.
AB  - Lymphocytopenia is associated with an adverse prognosis in heart failure (HF).
      The present study investigated whether lymphocytopenia results from activated
      lymphocyte autophagy/apoptosis, which reflects haemodynamic inefficiency and
      functional aerobic impairment in patients with HF. One hundred and twenty-seven
      patients with HF were divided into three groups: HF with non- (lymphocytes >=2000
      cells/MUl; n=45), mild (lymphocytes between >=1500 cells/MUl and <2000 cells/MUl;
      n=39) and severe (lymphocytes <1500 cells/MUl; n=43) lymphocytopenia. Lymphocyte
      autophagy/apoptosis, ventilatory/haemodynamic efficiencies and generic/disease
      specific quality of life were analysed in these patients with HF and 35 normal
      counterparts. The results demonstrated that patients with HF with severe
      lymphocytopenia had (i) increased G-protein-coupled receptor kinase-2 (GRK-2)
      levels, (ii) lower mammalian target of rapamycin (mTOR) levels with higher
      lysosome-associated membrane protein-2 (LAMP-2) expression and Acridine Orange
      (AO) staining, (iii) lower mitochondrial transmembrane potential with higher
      caspase-3 activation and phosphatidylserine (PS) exposure, and (iv) greater
      extents of adrenaline (epinephrine)-induced apoptosis in lymphocytes, and higher
      plasma noradrenaline (norepinephrine)/adrenaline, myeloperoxidase and interleukin
      6 concentrations than patients with HF without lymphocytopenia and normal
      counterparts did. Moreover, lymphocyte caspase-3 activation was an effect
      modifier, which modulated the correlation status between lymphocyte count and GRK
      2 level. Lymphocyte count was positively correlated with peak cardiac output and
      peak oxygen consumption (VO2peak) in patients with HF. In addition, HF with
      lymphocytopenia was accompanied by lower Short Form-36 physical/mental component
      scores and increased Minnesota Living with Heart Failure Questionnaire scores.
      Therefore, we conclude that increased sympathetic activation and oxidative
      stress/pro-inflammatory status cause lymphocytopenia by activating programmed
      lymphocyte death in patients with HF. Moreover, a low lymphocyte count correlates
      with reduced haemodynamics and aerobic capacity, which reflects poor
      generic/disease-specific quality of life in patients with HF.

PMID- 24863429
TI  - [Should the indication for thrombolytic therapy in patients with pulmonary
      embolism be extended?].

PMID- 24863431
TI  - Dual tracer imaging approach in assessing tumor biology and heterogeneity in
      neuroendocrine tumors: its correlation with tumor proliferation index and
      possible multifaceted implications for personalized clinical management
      decisions, with focus on PRRT.

PMID- 24863430
TI  - Patient-initiated electronic health record amendment requests.
AB  - BACKGROUND AND OBJECTIVE: Providing patients access to their medical records
      offers many potential benefits including identification and correction of errors.
      The process by which patients ask for changes to be made to their records is
      called an 'amendment request'. Little is known about the nature of such amendment
      requests and whether they result in modifications to the chart. METHODS: We
      conducted a qualitative content analysis of all patient-initiated amendment
      requests that our institution received over a 7-year period. Recurring themes
      were identified along three analytic dimensions: (1) clinical/documentation area,
      (2) patient motivation for making the request, and (3) outcome of the request.
      RESULTS: The dataset consisted of 818 distinct requests submitted by 181
      patients. The majority of these requests (n=636, 77.8%) were made to rectify
      incorrect information and 49.7% of all requests were ultimately approved. In 6.6%
      of the requests, patients wanted valid information removed from their record,
      27.8% of which were approved. Among all of the patients requesting a copy of
      their chart, only a very small percentage (approximately 0.2%) submitted an
      amendment request. CONCLUSIONS: The low number of amendment requests may be due
      to inadequate awareness by patients about how to make changes to their records.
      To make this approach effective, it will be important to inform patients of their
      right to view and amend records and about the process for doing so. Increasing
      patient access to medical records could encourage patient participation in
      improving the accuracy of medical records; however, caution should be used.

PMID- 24863432
TI  - Mesenchymal stem cell therapy for immune-modulation: the donor, the recipient,
      and the drugs in-between.
AB  - Adoptive transfer of cultured bone marrow stromal cells (mesenchymal stem cells
      also known as MSCs) is a promising new way to aid tissue regeneration and treat a
      wide variety of diseases where regulation of inflammatory responses is derailed.
      Although significant advances have been made in the field, pinpointing important
      mechanistic details about how MSCs function in vitro and in vivo, there are still
      many unanswered questions that need to be addressed before welcoming MSCs in the
      therapeutic arsenal of immune mediated diseases. In this viewpoint, we highlight
      and discuss a few factors that we believe are critical in terms of therapeutic
      success employing cultured MSCs. Selecting the right donor population, choosing
      the best culture conditions and picking the patient population that is most
      likely to give a favourable therapeutic response is just as important as
      considering interactions between MSCs and the combination of drugs in the
      recipient's body. Given the complexity of MSC-host interactions, it is also
      imperative to develop screening tools that account for as many variables as
      possible and predict precisely the in vivo response rates before MSCs enter the
      body. To achieve this, a multidisciplinary approach is required with
      comprehensive knowledge of basic MSC biology, immunology, pharmacology and good
      clinical practice. 

PMID- 24863433
TI  - Constraints to hydraulic acclimation under reduced light in two contrasting
      Phaseolus vulgaris cultivars.
AB  - Two cultivars of Phaseolus vulgaris L. were grown under three light levels to
      determine if hydraulic acclimation to light occurs in herbaceous annuals and
      whether intraspecific trade-offs constrain hydraulic traits. Acclimation occurred
      in response to reduced light and included decreased stomatal density (SD) and
      increased specific leaf area (SLA). Reduced light resulted in lower wood density
      (WD); decreased cavitation resistance, measured as the xylem pressure causing a
      50 % reduction in stem conductivity (P50); and increased hydraulic capacity,
      measured as average leaf mass specific transpiration (E(LM)). Significant or
      marginally significant trade-offs between P50 and WD, WD and E(LM), and E(LM) and
      P50 reflected variation due to both genotype and environmental effects. A trade
      off between WD and P50 within one cultivar indicated that morphological
      adjustment was constrained. Coordinated changes in WD, P50, and E(LM) within each
      cultivar in response to light were consistent with trade-offs constraining
      plasticity. A water-use efficiency (WUE, measured as delta(13)C) versus hydraulic
      capacity (E(LM)) trade-off was observed within each cultivar, further indicating
      that hydraulic trade-offs can constrain acclimation. Larger plants had lower
      hydraulic capacity (E(LM)) but greater cavitation resistance, WD, and WUE.
      Distinct hydraulic strategies were observed with the cultivar adapted to
      irrigated conditions having higher stomatal conductance and stem flow rates. The
      cultivar adapted to rain-fed conditions had higher leaf area and greater
      cavitation resistance. Hydraulic trade-offs were observed within the herbaceous
      P. vulgaris resulting from both genotype and environmental effects. Trade-offs
      within a cultivar reflected constraints to hydraulic acclimation in response to
      changing light. 

PMID- 24863434
TI  - Threshold response of stomatal closing ability to leaf abscisic acid
      concentration during growth.
AB  - Leaf abscisic acid concentration ([ABA]) during growth influences morpho
      physiological traits associated with the plant's ability to cope with stress. A
      dose-response curve between [ABA] during growth and the leaf's ability to
      regulate water loss during desiccation or rehydrate upon re-watering was
      obtained. Rosa hybrida plants were grown at two relative air humidities (RHs, 60%
      or 90%) under different soil water potentials (-0.01, -0.06, or -0.08MPa) or upon
      grafting onto the rootstock of a cultivar sustaining [ABA] at elevated RH.
      Measurements included [ABA], stomatal anatomical features, stomatal
      responsiveness to desiccation, and the ability of leaves, desiccated to varying
      degrees, to recover their weight (rehydrate) following re-watering. Transpiration
      efficiency (plant mass per transpired water) was also determined. Soil water
      deficit resulted in a lower transpiration rate and higher transpiration
      efficiency at both RHs. The lowest [ABA] was observed in well-watered plants
      grown at high RH. [ABA] was increased by soil water deficit or grafting, at both
      RHs. The growth environment-induced changes in stomatal size were mediated by
      [ABA]. When [ABA] was increased from the level of (well-watered) high RH-grown
      plants to the value of (well-watered) plants grown at moderate RH, stomatal
      responsiveness was proportionally improved. A further increase in [ABA] did not
      affect stomatal responsiveness to desiccation. [ABA] was positively related to
      the ability of dehydrated leaves to rehydrate. The data indicate a growth [ABA]
      related threshold for stomatal sensitivity to desiccation, which was not apparent
      either for stomatal size or for recovery (rehydration) upon re-watering. 

PMID- 24863436
TI  - Overexpression of ALTERNATIVE OXIDASE1a alleviates mitochondria-dependent
      programmed cell death induced by aluminium phytotoxicity in Arabidopsis.
AB  - Alternative oxidase (AOX) is a terminal oxidase found in all plants, and
      functions to maintain the electron flux and reduce the production of reactive
      oxygen species (ROS). Our previous study demonstrated that aluminium (Al)
      treatment could induce increased expression of the AOX1a gene, but the mechanism
      of how AOX1a participates in the regulation of Al-induced programmed cell death
      (PCD) is still not clear. To investigate the possible mechanism, mitochondrial
      ROS production and the behaviour of mitochondria, as well as caspase-3-like
      activation were monitored under Al treatment in wild-type (WT), AOX1a-lacking
      (aox1a), and AOX1a-overexpressing (AOX1a-OE) Arabidopsis. Our results showed that
      Al treatment increased the expression of AOX1a at both the transcriptional and
      translational levels. Overexpression of AOX1a reduced mitochondrial ROS
      production by maintaining the mitochondrial electron flux, and alleviated
      subsequent mitochondrial dysfunction and caspase-3-like activation in Al-induced
      PCD. Moreover, it was found that a change in AOX1a level could influence the
      expression levels of downstream functional genes that play protective roles in Al
      induced PCD. Experiments using mutants and inhibitors demonstrated that
      superoxide anion (O2 (-)) derived from mitochondria was involved in Al-induced
      upregulation of AOX1a gene expression. Taken together, these results indicated
      that overexpression of AOX1a alleviated Al-induced PCD by maintaining
      mitochondrial function and promoting the expression of protective functional
      genes, providing new insights into the signalling cascades that modulate the Al
      phytotoxicity mechanism. 

PMID- 24863437
TI  - Endoreduplication in the germinating embryo and young seedling is related to the
      type of seedling establishment but is not coupled with superoxide radical
      accumulation.
AB  - During germination, the embryo axis elongates and the radicle emerges through the
      surrounding structures of the seed. However, this elongation is not even along
      the axis, and it has been suggested that the region responsible for radicle
      protrusion is related to the type of subsequent seedling establishment. Eleven
      epigeal- and five hypogeal-type species were selected to study endoreduplication,
      a process coupled with cell elongation, in the radicle, hypocotyl-radicle
      transition zone, hypocotyl, and cotyledons of dry and germinating seeds, and in
      seedlings after radicle protrusion. Flow cytometry was used to establish the
      proportions of nuclei with different DNA contents, the mean C-value, and the
      (Sigma>2C)/2C ratio. Additionally, a nitroblue tetrazolium chloride test was
      applied to the embryos/seedlings in the dry state and during and after
      germination to localize superoxide radical (O2(*-)) accumulation, which has been
      suggested to play a role in cell elongation. Endoreduplication intensity varied
      in different species, in the embryo/seedling regions, and with the type of
      seedling establishment. In most of the cases, it was highest in the transition
      zone of epigeal species and in the hypocotyl in hypogeal species. O2(*-) was
      invariably produced during germination in the radicle, and additionally in the
      transition zone at the time of radicle protrusion; thus, it was not coupled with
      endoreduplication, and most probably played a role in defence against biotic and
      abiotic environmental stresses. These results provide information to aid in the
      selection of the most suitable plant material for molecular research on
      germination and for monitoring seed priming.

PMID- 24863435
TI  - Tomato PYR/PYL/RCAR abscisic acid receptors show high expression in root,
      differential sensitivity to the abscisic acid agonist quinabactin, and the
      capability to enhance plant drought resistance.
AB  - Abscisic acid (ABA) plays a crucial role in the plant's response to both biotic
      and abiotic stress. Sustainable production of food faces several key challenges,
      particularly the generation of new varieties with improved water use efficiency
      and drought tolerance. Different studies have shown the potential applications of
      Arabidopsis PYR/PYL/RCAR ABA receptors to enhance plant drought resistance.
      Consequently the functional characterization of orthologous genes in crops holds
      promise for agriculture. The full set of tomato (Solanum lycopersicum)
      PYR/PYL/RCAR ABA receptors have been identified here. From the 15 putative tomato
      ABA receptors, 14 of them could be grouped in three subfamilies that correlated
      well with corresponding Arabidopsis subfamilies. High levels of expression of
      PYR/PYL/RCAR genes was found in tomato root, and some genes showed predominant
      expression in leaf and fruit tissues. Functional characterization of tomato
      receptors was performed through interaction assays with Arabidopsis and tomato
      clade A protein phosphatase type 2Cs (PP2Cs) as well as phosphatase inhibition
      studies. Tomato receptors were able to inhibit the activity of clade A PP2Cs
      differentially in an ABA-dependent manner, and at least three receptors were
      sensitive to the ABA agonist quinabactin, which inhibited tomato seed
      germination. Indeed, the chemical activation of ABA signalling induced by
      quinabactin was able to activate stress-responsive genes. Both dimeric and
      monomeric tomato receptors were functional in Arabidopsis plant cells, but only
      overexpression of monomeric-type receptors conferred enhanced drought resistance.
      In summary, gene expression analyses, and chemical and transgenic approaches
      revealed distinct properties of tomato PYR/PYL/RCAR ABA receptors that might have
      biotechnological implications. 

PMID- 24863438
TI  - Nitrogen-use efficiency in maize (Zea mays L.): from 'omics' studies to metabolic
      modelling.
AB  - In this review, we will present the latest developments in systems biology with
      particular emphasis on improving nitrogen-use efficiency (NUE) in crops such as
      maize and demonstrating the application of metabolic models. The review
      highlights the importance of improving NUE in crops and provides an overview of
      the transcriptome, proteome, and metabolome datasets available, focusing on a
      comprehensive understanding of nitrogen regulation. 'Omics' data are hard to
      interpret in the absence of metabolic flux information within genome-scale
      models. These models, when integrated with 'omics' data, can serve as a basis for
      generating predictions that focus and guide further experimental studies. By
      simulating different nitrogen (N) conditions at a pseudo-steady state, the
      reactions affecting NUE and additional gene regulations can be determined. Such
      models thus provide a framework for improving our understanding of the metabolic
      processes underlying the more efficient use of N-based fertilizers. 

PMID- 24863439
TI  - Electricity generation and pollutant degradation using a novel biocathode coupled
      photoelectrochemical cell.
AB  - The photoelectrochemical cell (PEC) is a promising tool for the degradation of
      organic pollutants and simultaneous electricity recovery, however, current
      cathode catalysts suffer from high costs and short service lives. Herein, we
      present a novel biocathode coupled PEC (Bio-PEC) integrating the advantages of
      photocatalytic anode and biocathode. Electrochemical anodized TiO2 nanotube
      arrays fabricated on Ti substrate were used as Bio-PEC anodes. Field-emission
      scanning electron microscope images revealed that the well-aligned TiO2 nanotubes
      had inner diameters of 60-100 nm and wall-thicknesses of about 5 nm. Linear sweep
      voltammetry presented the pronounced photocurrent output (325 MUA/cm(2)) under
      xenon illumination, compared with that under dark conditions. Comparing studies
      were carried out between the Bio-PEC and PECs with Pt/C cathodes. The results
      showed that the performance of Pt/C cathodes was closely related with the
      structure and Pt/C loading amounts of cathodes, while the Bio-PEC achieved
      similar methyl orange (MO) decoloration rate (0.0120 min(-1)) and maximum power
      density (211.32 mW/m(2)) to the brush cathode PEC with 50 mg Pt/C loading (Brush
      PEC, 50 mg). The fill factors of Bio-PEC and Brush-PEC (50 mg) were 39.87% and
      43.06%, respectively. The charge transfer resistance of biocathode was 13.10
      Omega, larger than the brush cathode with 50 mg Pt/C (10.68 Omega), but smaller
      than the brush cathode with 35 mg Pt/C (18.35 Omega), indicating the comparable
      catalytic activity with Pt/C catalyst. The biocathode was more dependent on the
      nutrient diffusion, such as nitrogen and inorganic carbon, thus resulting in
      relatively higher diffusion resistance compared to the brush cathode with 50 mg
      Pt/C loading that yielded similar MO removal and power output. Considering the
      performance and cost of PEC system, the biocathode was a promising alternative
      for the Pt/C catalyst. 

PMID- 24863440
TI  - The amorphous silica-liquid water interface studied by ab initio molecular
      dynamics (AIMD): local organization in global disorder.
AB  - The structural organization of water at a model of amorphous silica-liquid water
      interface is investigated by ab initio molecular dynamics (AIMD) simulations at
      room temperature. The amorphous surface is constructed with isolated, H-bonded
      vicinal and geminal silanols. In the absence of water, the silanols have
      orientations that depend on the local surface topology (i.e. presence of concave
      and convex zones). However, in the presence of liquid water, only the strong
      inter-silanol H-bonds are maintained, whereas the weaker ones are replaced by H
      bonds formed with interfacial water molecules. All silanols are found to act as H
      bond donors to water. The vicinal silanols are simultaneously found to be H-bond
      acceptors from water. The geminal pairs are also characterized by the formation
      of water H-bonded rings, which could provide special pathways for proton
      transfer(s) at the interface. The first water layer above the surface is overall
      rather disordered, with three main domains of orientations of the water
      molecules. We discuss the similarities and differences in the structural
      organization of the interfacial water layer at the surface of the amorphous
      silica and at the surface of the crystalline (0 0 0 1) quartz surface.

PMID- 24863441
TI  - Reinvigorating healthcare policies and practices.

PMID- 24863442
TI  - What Edmund Wilson can teach us about health system transformation.

PMID- 24863443
TI  - Assessing primary healthcare using pan- Canadian indicators of health and health
      system performance.
AB  - Updated primary healthcare (PHC) indicators are now available for use across
      Canada. The Canadian Institute for Health Information identified and updated two
      sets of priority indicators - a policy set to meet the needs of policy makers and
      a provider set to meet the needs of providers of PHC at the practice and
      organization levels. A total of 51 indicator definitions were updated to ensure
      that they are measurable and operational, align with clinical practice guidelines
      and available data sources and reflect important dimensions of PHC performance in
      Canada. 

PMID- 24863445
TI  - In conversation with Chris Eagle.

PMID- 24863444
TI  - "Avoidable" emergency department transfers from long-term care homes: a brief
      review.

PMID- 24863446
TI  - "If you're not keeping score, you're just practising": a lean healthcare program
      evaluation framework.

PMID- 24863447
TI  - Building sector-wide bridges to improve patient flow and care.
AB  - Healthcare system transformation relies upon innovative solutions that build
      sector-wide bridges and challenge conventional thinking to benefit patients and
      families. Providence Healthcare - a Toronto leader in rehabilitation - is doing
      this by partnering with the Toronto Central Local Health Integration Network
      (LHIN), community care access centres and four acute care hospitals to improve
      system-wide patient flow. This article explains how Providence's Transformation
      by Design demonstration project was launched and sustained through engaging key
      stakeholders, and is now demonstrating positive, measurable results on key
      metrics in patient flow in Toronto. 

PMID- 24863449
TI  - Drug information systems: evolution of benefits with system maturity.
AB  - Benefits from information and communication technology tend to grow over time as
      system use matures. This study examines pharmacists' experiences with provincial
      drug information systems (DIS) across Canada. At the time of survey, two
      provinces had more mature DIS (more than five years) and three provinces had less
      mature DIS (five years or less). 

PMID- 24863448
TI  - Development and evaluation of a "working together" framework and a tool kit to
      enhance inter-organizational relationships in healthcare.
AB  - Healthcare is in a constant state of change and evolution driven by a multitude
      of complex factors and interactions. Consequently, organizations, teams and
      individuals in healthcare have to habitually realign their working relationships.
      Furthermore, research has shown that "working together" relationships fail in the
      absence of a defined framework. In this research, a novel framework and a tool
      kit for working together have been developed and evaluated. The framework has a
      formal process to articulate the intended purpose/outcome, clearly align the type
      of working relationship with the purpose and identify the barriers and
      facilitators to working relationships in healthcare. 

PMID- 24863450
TI  - Enhancing care for individuals with mobility impairments: lessons learned in the
      implementation of a primary care-based mobility clinic.
AB  - Persons with mobility impairments experience significant barriers to primary
      healthcare. This study examines key lessons learned, as derived from interviews
      with referral sources and Centre for Family Medicine Mobility Clinic team
      members, in the development and implementation of a primary care-based mobility
      clinic aimed at reducing these barriers, and it reflects on the implications of
      this model of care on the system of care. Results highlight the importance of
      accessibility, specialized equipment, promotional activities and management
      support as well as challenges reflected by system barriers to care. The results
      of this study have implications for the application of this model of care in
      other settings. 

PMID- 24863451
TI  - Our patients expect more (and so do we): it's time to rethink patient
      satisfaction.
AB  - A current focus of healthcare organizations and legislation requires hospitals to
      place more importance on patient experience and satisfaction than ever before.
      Institutional patient satisfaction survey tools yield data that represent
      approximately 5% of patients and may not represent the typical patient
      experience. Moreover, our research demonstrates that only 1% of surveyed
      providers rely on these data as their primary source of patient satisfaction
      feedback. The low response rate, the delayed timing of the feedback and a lack of
      usability for clinicians raise questions about the value of these tools to front
      line healthcare providers - those most responsible for the patients' experience
      of care. 

PMID- 24863452
TI  - Rapid dissemination of a critical care protocol using basic information
      technology prior to a rave.

PMID- 24863453
TI  - Small changes produce large gains in efficiency: a case study from Ross Memorial
      Hospital.
AB  - Healthcare is now more challenged to provide excellent care, while also
      increasing efficiency with more limited resources. The recent introduction of
      Ontario's funding reform challenges hospitals to increase the efficiency of
      specific procedures by providing funding based on patient volumes. The cataract
      surgery program at Ross Memorial Hospital, in Lindsay, Ontario, is an example of
      how a program designed a few years ago with a focus on patient care and
      efficiency managed to become substantially more efficient by introducing a series
      of small changes. 

PMID- 24863455
TI  - Flexible polyimide films hybrid with functionalized boron nitride and graphene
      oxide simultaneously to improve thermal conduction and dimensional stability.
AB  - Coupling agent-functionalized boron nitride (f-BN) and glycidyl methacrylate
      grafted graphene (g-TrG) are simultaneously blended with polyimide (PI) to
      fabricate a flexible, electrically insulating and thermally conductive PI
      composite film. The silk-like g-TrG successfully fills in the gap between PI and
      f-BN to complete the thermal conduction network. In addition, the strong
      interaction between surface functional groups on f-BN and g-TrG contributes to
      the effective phonon transfer in the PI matrix. The thermal conductivity (TC) of
      the PI/f-BN composite films containing additional 1 wt % of g-TrG is at least
      doubled to the value of PI/f-BN and as high as 16 times to that of the pure PI.
      The hybrid film PI/f-BN-50/g-TrG-1 exhibits excellent flexibility, sufficient
      insulating property, the highest TC of 2.11 W/mK, and ultralow coefficient of
      thermal expansion of 11 ppm/K, which are perfect conditions for future flexible
      substrate materials requiring efficient heat dissipation. 

PMID- 24863454
TI  - Peroxiredoxin 1 participates in ischemia-triggered endothelial polarization.

PMID- 24863456
TI  - Activity and ecological implications of maize-expressed transgenic endo-1,4-beta
      D-glucanase in agricultural soils.
AB  - Plant expression of thermostable endoglucanase (E1) has been proposed for
      improved conversion of lignocellulose to ethanol for fuel production. Residues of
      E1-expressing maize may affect ecological services (e.g., C mineralization and
      biogeochemical cycling) on soils where they occur. Therefore, the activity of
      residual E1 was investigated using soils amended with bacterial and plant
      solubilized E1 compared with soil endogenous activity and residual activity from
      a mesostable cellulase (Aspergillus and Trichoderma spp.). An optimized
      analytical method involving a carboxymethyl cellulose substrate and
      dinitrosalicylic acid detection effectively assayed endoglucanase activity in
      amended and unamended soils and was used for determining E1 activity in 3
      representative soils. The effect of E1 on soil carbon mineralization was
      determined by comparing CO(2) evolution from soils amended with transgenic E1
      expressing and wild-type maize tissue. Extraction and recovery of the mesostable
      comparator, bacterial E1, and plant-soluble E1 showed nearly complete loss of
      exogenous endoglucanase activity within a 24-h period. Carbon mineralization
      indicated no significant difference between soils amended with either the
      transgenic E1 or wild-type maize tissue. These results indicate that maize
      residues expressing up to 30 ug E1/g tissue negligibly affect soil endoglucanase
      activity and CO(2) respiration for representative soils where transgenic E1 maize
      may be grown.

PMID- 24863457
TI  - Breast conservative surgery in breast cancer: simple can be harder than complex.

PMID- 24863458
TI  - The type VI protein secretion system contributes to biofilm formation and seed-to
      seedling transmission of Acidovorax citrulli on melon.
AB  - The type VI protein secretion system (T6SS) is essential for the virulence of
      several Gram-negative bacteria. In this study, we identified a T6SS gene cluster
      in Acidovorax citrulli, a plant-pathogenic bacterium that causes bacterial fruit
      blotch (BFB) of cucurbits. One T6SS cluster, of approximately 25 kb in length and
      comprising 17 genes, was found in the A. citrulli AAC00-1 genome. Seventeen A.
      citrulli mutants were generated, each with a deletion of a single T6SS core gene.
      There were significant differences in BFB seed-to-seedling transmission between
      wild-type A. citrulli strain, xjl12, and DeltavasD, DeltaimpK, DeltaimpJ and
      DeltaimpF mutants (71.71%, 9.83%, 8.41%, 7.15% and 5.99% BFB disease index,
      respectively). In addition, we observed that these four mutants were reduced in
      melon seed colonization and biofilm formation; however, they were not affected in
      virulence when infiltrated into melon seedling tissues. There were no significant
      differences in BFB seed-to-seedling transmission, melon tissue colonization and
      biofilm formation between xjl12 and the other 13 T6SS mutants. Overall, our
      results indicate that T6SS plays a role in seed-to-seedling transmission of BFB
      on melon. 

PMID- 24863460
TI  - Speed dependence of thermochemical nanolithography for gray-scale patterning.
AB  - Thermochemical nanolithography (TCNL) is a high-resolution lithographic technique
      and, owing to its fast speed, versatility, and unique ability to fabricate
      arbitrary, gray-scale nanopatterns, this scanning probe technique is relevant
      both for fundamental scientific research as well as for nanomanufacturing
      applications. In this work, we study the dependence of the TCNL driven chemical
      reactions on the translation speed of the thermal cantilever. The experimental
      data compares well with a model of the chemical kinetics for a first-order
      reaction. The impact of higher order reactions on the optimization of TCNL is
      addressed. The reported quantitative description of the speed dependence of TCNL
      is exploited and illustrated by fabricating controlled gradients of chemical
      concentration. 

PMID- 24863461
TI  - Lean mass modulates glomerular filtration rate in males of normal and extreme
      body composition.
AB  - BACKGROUND: Understanding determinants of glomerular filtration rate (GFR) is
      important in aiding prediction and interpretation of kidney function. Body
      composition is known to affect GFR but is not included in current screening of
      kidney disease. We investigated the association between GFR and body composition
      in healthy young men with differing body mass but without known diabetes or
      kidney injury. METHODS: Three groups were recruited: normal BMI (n = 22) with a
      body mass index (BMI) <25 kg/m(2) , muscular (n = 23) with BMI >=30 kg/m(2) and
      bioelectrical impedance body fat <=20% and obese (n = 22) with BMI >=30 kg/m(2)
      and bioelectrical impedance body fat >=30%. Dietary analyses, GFR clearance by
      (99m) Tc-DTPA, urine protein and body composition by dual-energy X-ray
      absorptiometry were measured in all participants. Linear and nonlinear
      associations of constituents of body composition with GFR were assessed. RESULTS:
      Muscular men had a higher GFR (mean 186.4 mL/min; 95% CI 171.7-201.1) than normal
      BMI and obese groups (P = 0.0007). Urine protein and albumin excretion were not
      elevated in any participants. On multiple regression analysis (r(2) = 0.60), the
      variables with strong associations with GFR were age (P = 0.0009) and lean mass
      (P = 0.0001). Fat mass, protein intake and smoking status were not associated.
      Skeletal muscle mass correlated significantly with GFR in all subgroups.
      CONCLUSION: Age and lean mass were strong determinants of GFR. Estimates of GFR
      should therefore be indexed to an estimate of lean mass.

PMID- 24863462
TI  - Vitreoretinal interface changes in geographic atrophy.
AB  - PURPOSE: Geographic atrophy (GA) is the end-stage manifestation of atrophic age
      related macular degeneration (AMD). The disease progresses slowly over time,
      eventually causing loss of central vision. Its cause and pathomechanism are not
      fully known. Previous studies have suggested that vitreoretinal traction (VRT)
      may contribute to the progression of neovascular AMD. The aim of this study was
      to examine whether an association between changes at the vitreoretinal interface
      (VRI), in particular traction (VRT), and the characteristics and progression of
      GA in eyes with dry AMD can be established. DESIGN: Clinic-based prospective
      cohort study. PARTICIPANTS: A total of 97 patients (age range, 61-90 years; mean,
      78.4 years) with GA secondary to dry AMD were enrolled. Patients exhibiting
      neovascular signs on fluorescein angiography in either eye were excluded.
      METHODS: The VRI changes were examined using spectral-domain optical coherence
      tomography (SD-OCT). Characteristics of GA were examined using fundus
      autofluorescence (FAF) imaging. All imaging was performed using a Spectralis
      SLO+OCT device (Heidelberg Engineering, Heidelberg, Germany); GA area was
      measured using the Region Finder (Heidelberg Engineering) software native to the
      Spectralis platform. MAIN OUTCOME MEASURES: Area and increase in area of GA.
      RESULTS: A total of 97 eyes were examined. Vitreoretinal traction was found in 39
      eyes (40%). The GA area at baseline was 6.65+/-5.64 mm(2) in eyes with VRT and
      5.73+/-4.72 mm(2) in eyes with no VRT. The annual rate of progression of GA area
      progression was 2.99+/-0.66 mm(2) in eyes with VRT and 1.45+/-0.67mm(2) in eyes
      without VRT. Differences between groups in both parameters were statistically
      significant (n = 97 total number of eyes; P<0.001). Multiple regression analysis
      confirmed this finding (B = 0.714, P<0.001; F3,93 = 72.542, P<0.001; adjusted
      R(2) = 0.691) CONCLUSIONS: Our results indicate an association between VRT and an
      increased rate of progression of GA area in dry AMD. Monitoring VRT may
      contribute to an improved estimate of the prospective time of visual loss and to
      a better timing of emerging therapies in dry AMD.

PMID- 24863459
TI  - Untangling the hybrid nature of modern pig genomes: a mosaic derived from
      biogeographically distinct and highly divergent Sus scrofa populations.
AB  - The merging of populations after an extended period of isolation and divergence
      is a common phenomenon, in natural settings as well as due to human interference.
      Individuals with such hybrid origins contain genomes that essentially form a
      mosaic of different histories and demographies. Pigs are an excellent model
      species to study hybridization because European and Asian wild boars diverged
      ~1.2 Mya, and pigs were domesticated independently in Europe and Asia. During the
      Industrial Revolution in England, pigs were imported from China to improve the
      local pigs. This study utilizes the latest genomics tools to identify the origin
      of haplotypes in European domesticated pigs that are descendant from Asian and
      European populations. Our results reveal fine-scale haplotype structure
      representing different ancient demographic events, as well as a mosaic
      composition of those distinct histories due to recently introgressed haplotypes
      in the pig genome. As a consequence, nucleotide diversity in the genome of
      European domesticated pigs is higher when at least one haplotype of Asian origin
      is present, and haplotype length correlates negatively with recombination
      frequency and nucleotide diversity. Another consequence is that the inference of
      past effective population size is influenced by the background of the haplotypes
      in an individual, but we demonstrate that by careful sorting based on the origin
      of haplotypes, both distinct demographic histories can be reconstructed. Future
      detailed mapping of the genomic distribution of variation will enable a targeted
      approach to increase genetic diversity of captive and wild populations, thus
      facilitating conservation efforts in the near future. 

PMID- 24863463
TI  - Retinal neovascularization and endogenous fungal endophthalmitis in intravenous
      drug users.

PMID- 24863464
TI  - [Attitudes of medical staff potentially participating in the organ donation
      process towards organ donation and transplantation in Bavaria].
AB  - BACKGROUND: Organ donation rates in Germany are lower than in other countries and
      have declined further after manipulations of the waiting lists in some German
      transplant centers became public. Attitudes and commitment of medical personnel
      are crucial for successful organ donation. Therefore, we studied the attitudes of
      hospital staff towards organ donation and transplantation. METHOD: In 50 Bavarian
      hospitals, medical professionals working in units relevant to organ donation were
      asked to respond to an anonymous questionnaire. RESULTS: 2983 questionnaires
      could be evaluated. The majority of all respondents had a positive attitude
      towards organ donation; 71 % were willing to donate their organs after brain
      death and 57 % were willing to accept a transplant in case of organ failure.
      Rates of positive attitude were lower among nurses than among physicians. 28 %
      indicated that recent developments had a negative impact on their attitude and of
      those approximately half evaluated the work of transplant centers negatively.
      Overall only 23 % considered organ allocation as fair. The majority of nurses and
      a large proportion of physicians considered themselves as not well informed.
      CONCLUSION: The current loss of confidence into organ donation and
      transplantation also affects the attitude of medical personnel. Intensified
      measures of information and full transparency of all procedures are urgently
      needed.

PMID- 24863466
TI  - Single implant-supported crowns in the aesthetic zone: patient satisfaction with
      aesthetic appearance compared with appraisals by laypeople and dentists.
AB  - OBJECTIVE: To appraise the patients' satisfaction with aesthetic outcomes
      following an implant restoration in the anterior maxilla as compared to
      appraisals made by dentists and laypeople. MATERIAL AND METHODS: Randomly
      selected patients (n = 116) restored with an implant-retained crown in the
      anterior maxilla were invited to rate their satisfaction with aesthetic outcomes
      using a questionnaire containing seven criteria, each graded from excellent to
      poor. Projected images of the patient smiles were appraised by dentists (n = 8)
      and laypeople (n = 6) using the same assessment criteria in a room setting. In
      addition, the laypeople judged the same cases on printed 10 * 15 cm photographs
      in a separate setting. Jemt papilla scores, pink aesthetic score (PES) and white
      esthetic score (WES) were assigned by the dentists. Differences in the levels of
      satisfaction between the patient, and appraisals by the dentists and the
      laypeople were compared using non-parametric statistical tests. RESULTS:
      Patients' opinions of their aesthetic appearance following the placement of a
      single implant-supported crown in the aesthetic zone were in general very
      favourable. The laypeople were more critical than the dentists when the aesthetic
      outcomes were appraised on magnified images projected onto a screen. Laypeople
      became less critical when evaluating the aesthetic outcomes on printed
      photographs compared to appraisals on a screen. Patient satisfaction with their
      aesthetic appearance differed from dentists' and laypeople's appraisals.
      CONCLUSION: Factors other than the actual aesthetic outcome itself appear to
      influence patients' satisfaction with their end results. Laypeople's appraisal is
      influenced by the magnification and method used for appraising the aesthetic
      outcomes.

PMID- 24863467
TI  - EAARN score, a predictive score for mortality in patients receiving cardiac
      resynchronization therapy based on pre-implantation risk factors.
AB  - AIMS: The beneficial effects of CRT in patients with advanced heart failure, wide
      QRS, and low LVEF have been clearly established. Nevertheless, mortality remains
      high in some patients. The aims of our study were to identify the predictors of
      mortality in patients treated with CRT and to design a risk score for mortality.
      METHODS AND RESULTS: A cohort of 608 consecutive patients treated with CRT from
      2000 to 2011 in our centre was prospectively analysed. Baseline clinical and
      echocardiography variables were analysed and mortality data were collected.
      During a mean follow-up of 36.2 +/- 29.2 months, 174 patients died: 123/174 (71%)
      due to cardiovascular causes, 25/174 (14%) non-cardiac causes, and 26/174 (15%)
      unknown aetiology. In a multivariate analysis the predictors of mortality were
      NYHA class IV [hazard ratio (HR) 2.54, 95% confidence interval (CI) 1.7-3.7, P <
      0.001], glomerular filtration rate (GFR) <60 mL/min/1.73 m2 (HR 1.61, 95% CI 1.14
      2.30, P = 0.008), AF (HR 1.67, 95% CI 1.19-2.3, P = 0.01), age >=70 years (HR
      1.44, (95% CI 1.04-2.00, P = 0.02), and LVEF <22% (HR 1.83, 95% CI 1.33-2.52, P
      <= 0.001). The EAARN score (EF, Age, AF, Renal dysfunction, NYHA class IV)
      summarizes the predictors. Each additional predictor increased the mortality: one
      predictor, HR 3.28 (95% CI 1.37-7.8, P = 0.008); two, HR 5.23 (95% CI 2.24-12.10,
      P < 0.001); three, HR 9.63 (95% CI 4.1-22.60, P < 0.001); and four or more, HR
      14.38 (95% CI 5.8-35.65, P < 0.001). CONCLUSION: The predictors of mortality have
      a significant add-on predictive effect on mortality. The EAARN score could be
      useful to stratify the prognosis of CRT patients.

PMID- 24863468
TI  - Dietary supplementation with resveratrol protects against striatal dopaminergic
      deficits produced by in utero LPS exposure.
AB  - The purpose of this study was to determine the effect of dietary supplementation
      with the anti-inflammatory compound resveratrol in pregnant dams on
      lipopolysaccharide (LPS)-induced dopaminergic deficits in pups exposed to LPS in
      utero. Gravid female rats were fed with a resveratrol-enriched diet during
      gestational days 3-22.5 (E3-E22.5) and received an intraperitoneal (i.p.)
      injection of 1mg/kg LPS at E10.5. The striata were isolated from the pups at
      postnatal days 10 (P10) and P21. LPS-induced dopaminergic deficits were noted at
      P21, but not P10. These DA deficits at P21 were exhibited by a loss of DA and DA
      metabolite [3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA)]
      levels and tyrosine hydroxylase (TH) expression in the striatum. The LPS-induced
      loss of DA, DA metabolites, and TH expression were attenuated in the striata of
      pups from the dams fed with the resveratrol-supplemented diet. These data suggest
      that a resveratrol-supplemented diet may restore homeostasis of the striatal DA
      neuronal system following disruption by LPS. 

PMID- 24863469
TI  - Localization of protein kinase C isoforms in the optic pathway of mouse embryos
      and their role in axon routing at the optic chiasm.
AB  - Protein kinase C (PKC) plays a key role in many receptor-mediated signaling
      pathways that regulate cell growth and development. However, its roles in guiding
      axon growth and guidance in developing neural pathways are largely unknown. To
      investigate possible functions of PKC in the growth and guidance of axons in the
      optic chiasm, we first determined the localization of major PKC isoforms in the
      retinofugal pathway of mouse embryos, at the stage when axons navigate through
      the midline. Results showed that PKC was expressed in isoform specific patterns
      in the pathway. PKC-alpha immunoreactivity was detected in the chiasm and the
      optic tract. PKC-betaIotaIota was strong in the optic stalk but was attenuated on
      axons in the diencephalon. Immunostaining for PKC-epsilon showed a colocalization
      in the chiasmatic neurons that express a surface antigen stage specific embryonic
      antigen-1 (SSEA-1). These chiasmatic neurons straddled the midline of the optic
      chiasm, and have been shown in earlier studies a role in regulation of axon
      growth and guidance. Expression levels of PKC-betaIota, -delta and -gamma were
      barely detectable in the pathway. Blocking of PKC signaling with Ro-32-0432, an
      inhibitor specific for PKC-alpha and -beta at nanomolar concentration, produced a
      dramatic reduction of ipsilateral axons from both nasal retina and temporal
      crescent. We conclude from these studies that PKC-alpha and -betaIotaIota are the
      predominant forms in the developing optic pathway, whereas PKC-epsilon is the
      major form in the chiasmatic neurons. Furthermore, PKC-alpha and -betaIotaIota
      are likely involved in signaling pathways triggered by inhibitory molecules at
      the midline that guide optic axons to the uncrossed pathway.

PMID- 24863470
TI  - Considerations for conducting imaging studies in support of developmental
      toxicology studies for regulatory submission.
AB  - Preclinical imaging technologies are increasingly being applied to developmental
      toxicology studies in drug development to determine potential compound toxicity.
      Although most of these studies are conducted in a non-regulatory setting, there
      is interest in performing these imaging studies under applicable regulations, for
      example Good Laboratory Practices (GLP), to support regulatory decisions
      concerning drug safety. This manuscript will describe regulations and processes
      to consider when bringing an imaging technology into GLP compliance. 

PMID- 24863471
TI  - Assessment of fetal exposure risk following seminal excretion of a therapeutic
      IgG4 (T-IgG4) monoclonal antibody using a rabbit model.
AB  - Studies were conducted in New Zealand White rabbits to assess the seminal
      transfer, vaginal absorption, and placental transfer of a therapeutic monoclonal
      antibody (T-IgG4). T-IgG4 was administered by intravenous injection (IV) in males
      and by IV and intravaginal routes in females. Low levels of T-IgG4 were excreted
      into seminal plasma (100- to 370-fold lower than serum concentrations) and
      absorbed following vaginal dosing (three orders of magnitude lower than IV
      administration). On gestation day 29 (GD29), fetal serum T-IgG4 levels were 1.5
      fold greater than maternal levels following IV dosing. The fetal T-IgG4 exposure
      ratio for seminal transfer vs. direct maternal IV dosing was estimated to be
      1.3*10(-8). Applying human serum T-IgG4 exposure data to the model, the estimated
      human T-IgG4 serum concentration from seminal transfer was 3.07*10(-7)MUg/mL, an
      exposure level at least 1000-fold lower than the T-IgG4-ligand dissociation
      constant (Kd) and at least seven orders of magnitude lower than the in vivo
      concentration producing 20% inhibition of the target (EC20). These data indicate
      that excretion of a T-IgG4 into semen would not result in a biologically
      meaningful exposure risk to the conceptus of an untreated partner. 

PMID- 24863472
TI  - Proteomic analysis of Rhizoctonia solani AG-1 sclerotia maturation.
AB  - Rhizoctonia solani (R. solani), a soil-borne necrotrophic pathogen, causes
      various plant diseases. Rhizoctonia solani is a mitosporic fungus, the sclerotium
      of which is the primary inoculum and ensures survival of the fungus during the
      offseason of the host crop. Since the fungus does not produce any asexual or
      sexual spores, understanding the biology of sclerotia is important to examine
      pathogen ecology and develop more efficient methods for crop protection. Here,
      one- and two-dimensional gel electrophoresis (1-DE and 2-DE, respectively) were
      used to examine protein regulation during the maturation of fungal sclerotia. A
      total of 75 proteins (20 proteins from 1-DE using matrix-assisted laser
      desorption/ionization (MALDI)-time of flight (TOF) mass spectrometry (MS) and 55
      proteins from 2-DE using MALDI-TOF MS or MALDI-TOF/TOF MS) were differentially
      expressed during sclerotial maturation. The identified proteins were classified
      into ten categories based on their biological functions, including genetic
      information processing, carbohydrate metabolism, cell defense, amino acid
      metabolism, nucleotide metabolism, cellular processes, pathogenicity and
      mycotoxin production, and hypothetical or unknown functions. Interestingly, two
      vacuole function-related proteins were highly up-regulated throughout sclerotial
      maturation, which was confirmed at the transcript level by reverse transcriptase
      polymerase chain reaction (RT-PCR) analysis. These findings contribute to our
      understanding of the biology of R. solani sclerotia. 

PMID- 24863474
TI  - Molecular cloning and functional analysis of a H(+)-dependent phosphate
      transporter gene from the ectomycorrhizal fungus Boletus edulis in southwest
      China.
AB  - Phosphate transporters (PTs), as entry points for phosphorus (P) in organisms,
      are involved in a number of P nutrition processes such as phosphate uptake,
      transport, and transfer. In the study, a PT gene 1632 bp long (named BePT) was
      cloned, identified, and functionally characterized from Boletus edulis. BePT was
      expected to encode a polypeptide with 543 amino acid residues. The BePT
      polypeptide belonged to the major facilitator superfamily and showed a high
      degree of sequence identity to the Pht1 family. A topology model revealed that
      BePT exhibited 12 transmembrane helices, divided into two halves, and connected
      by a large hydrophilic loop in the middle. A yeast mutant complementation
      analysis suggested that BePT was a functional PT which mediated orthophosphate
      uptake of yeast at micromolar concentrations. Green fluorescent protein-BePT
      fusion proteins expressed were extensively restricted to the plasma membrane in
      BePT transformed yeast, and its activity was dependent on electrochemical
      membrane potential. In vitro, quantitative PCR confirmed that the expression of
      BePT was significantly upregulated at lower phosphorus availability, which may
      enhance phosphate uptake and transport under phosphate starvation. Our results
      suggest that BePT plays a key role in phosphate acquisition in the
      ectomycorrhizal fungus B. edulis. 

PMID- 24863473
TI  - Localization and speciation of arsenic in Glomus intraradices by synchrotron
      radiation spectroscopic analysis.
AB  - The protective mechanisms employed by arbuscular mycorrhizal fungi (AMF) to
      reduce the toxic effects of arsenic on host plants remain partially unknown. The
      goal of this research was identifying the in situ localization and speciation of
      arsenic (As) in the AM fungus Rhizophagus intraradices [formerly named Glomus
      intraradices] exposed to arsenate [As(V)]. By using a two-compartment in vitro
      fungal cultures of R. intraradices-transformed carrot roots, microspectroscopic X
      ray fluorescence (MU-XRF), and microspectroscopic X-ray absorption near edge
      structure (MU-XANES), we observed that As(V) is absorbed after 1 h in the hyphae
      of AMF. Three hours after exposure a decrease in the concentration of As was
      noticed and after 24 and 72 h no detectable As concentrations were perceived
      suggesting that As taken up was pumped out from the hyphae. No As was detected
      within the roots or hyphae in the root compartment zone three or 45 h after
      exposure. This suggests a dual protective mechanism to the plant by rapidly
      excluding As from the fungus and preventing As translocation to the plant root.
      MU-XANES data showed that gradual As(V) reduction occurred in the AM hyphae
      between 1 and 3 h after arsenic exposure and was completed after 6 h. Principal
      component analysis (PCA) and linear combination fitting (LCF) of MU-XANES data
      showed that the dominant species after reduction of As(V) by R. intraradices
      extra-radical hyphal was As(III) complexed with a reduced iron(II) carbonate
      compound. The second most abundant As species present was As(V)-iron hydroxides.
      The remaining As(III) compounds identified by the LCF analyses suggested these
      molecules were made of reduced As and S. These results increase our knowledge on
      the mechanism of As transport in AMF and validate our hypotheses that R.
      intraradices directly participates in arsenic detoxification. These fungal
      mechanisms may help AMF colonized plants to increase their tolerance to As at
      contaminated sites. 

PMID- 24863475
TI  - Formation of arthroconidia during regeneration and selection of transformed
      Epichloe festucae protoplasts.
AB  - Transformation is an essential tool for modern fungal research and has played a
      fundamental role in gaining insight into gene function. Polyethylene glycol (PEG)
      mediated transformation of protoplasts is the most commonly used method for
      genetic transformation of filamentous fungi. Selectable marker genes, that confer
      resistance to antibiotics, are generally incorporated with the DNA of interest,
      allowing transformed cells to grow through the antibiotic overlay. Colonies
      arising from transformed fungal cells are sub-cultured and further analysed.
      However, the morphological state of the fungal cells during the transformation
      procedure has been largely overlooked. We investigated the morphological
      appearance of transformed fungal cells prior to their emergence through the
      antibiotic overlay. Hyphae appeared to segment and bulge, reminiscent of
      arthroconidia, an asexual spore typically produced by segmentation of pre
      existing hyphae. Selective expression of eGFP under the control of a spore
      specific promoter, PcatA, in these cells confirmed their spore-like nature.
      Reducing the oxygen availability to surface-grown cultures partially
      recapitulated this morphological form. A GFP fusion to the cell wall integrity
      MAP kinase MpkA localised to the arthroconidia nuclei suggesting the cell wall
      integrity signalling pathway modulates cell wall stress responses in
      arthroconidia. This dramatic morphological change was also observed in
      transformed Magnaporthe oryzae cells suggesting it may be a more general
      phenomenon in filamentous fungi. Given the changes in cellular structure and
      spore-like appearance, these observations may have technical implications for
      deleting genes involved in these processes in Epichloe festucae and, more
      broadly, a range of fungal species. 

PMID- 24863476
TI  - Bark and ambrosia beetles (Curculionidae: Scolytinae), their phoretic mites
      (Acari) and associated Geosmithia species (Ascomycota: Hypocreales) from Virgilia
      trees in South Africa.
AB  - Bark and ambrosia beetles are ecologically and economically important
      phloeophagous insects that often have complex symbiotic relationships with fungi
      and mites. These systems are greatly understudied in Africa. In the present study
      we identified bark and ambrosia beetles, their phoretic mites and their main
      fungal associates from native Virgilia trees in the Cape Floristic Region (CFR)
      of South Africa. In addition, we tested the ability of mites to feed on the
      associated fungi. Four species of scolytine beetles were collected from various
      Virgilia hosts and from across the CFR. All were consistently associated with
      various Geosmithia species, fungi known from phloeophagous beetles in many parts
      of the world, but not yet reported as Scolytinae associates in South Africa. Four
      beetle species, a single mite species and five Geosmithia species were recovered.
      The beetles, Hapalogenius fuscipennis, Cryphalini sp. 1, and Scolytoplatypus
      fasciatus were associated with a single species of Elattoma phoretic mite that
      commonly carried spores of Geosmithia species. Liparthrum sp. 1 did not carry
      phoretic mites. Similar to European studies, Geosmithia associates of beetles
      from Virgilia were constant over extended geographic ranges, and species that
      share the same host plant individual had similar Geosmithia communities. Phoretic
      mites were unable to feed on their Geosmithia associates, but were observed to
      feed on bark beetle larvae within tunnels. This study forms the first African
      centred base for ongoing global studies on the associations between arthropods
      and Geosmithia species. It strengthens hypotheses that the association between
      Scolytinae beetles and dry-spored Geosmithia species may be more ubiquitous than
      commonly recognised. 

PMID- 24863477
TI  - Vegetative compatibility groups and sexual reproduction among Spanish Monilinia
      fructicola isolates obtained from peach and nectarine orchards, but not Monilinia
      laxa.
AB  - The frequency of occurrence of Monilinia fructicola in the Ebro Valley, Spain has
      increased since its first appearance in 2006, and M. fructicola has displaced
      Monilinia laxa, the native species which is the main cause of brown rot in
      peaches in this valley. In order to determine the characteristics that may be
      related to the displacement, we studied the capacity to generate new genotypic
      combinations of M. fructicola under laboratory conditions. The morphology and
      parasitic ability from ten field isolates of M. fructicola and M. laxa collected
      from three different orchards in the valley, and sampling from five different
      lesions were studied. Nitrate-non-utilising (nit) mutants were generated in order
      to test the isolates for vegetative compatibility which was done by assessing
      their colony growth when cultured singly or in pairs on media that contained
      different nitrogen sources. For the M. fructicola isolates, five vegetative
      compatibility groups (VCGs) were identified using the nit mutants and six VCGs
      were identified when they were grown on potato dextrose agar dishes. In all
      instances, the vegetatively compatible M. fructicola isolates came mainly from
      the same orchard. Only one VCG displays the same morphological and competition
      characteristics. No VCGs were identified among the M. laxa isolates. We did not
      find any apothecia of M. laxa and M. fructicola isolates in the soil of the three
      orchards, but we were able to produce apothecia of M. fructicola in the
      laboratory. Our finding of sexual reproduction and VCGs in the M. fructicola
      isolates suggests that the genetic variability of M. fructicola could be
      maintained by sexual and/or parasexual recombination. 

PMID- 24863478
TI  - Molecular phylogeny of Rigidoporus microporus isolates associated with white rot
      disease of rubber trees (Hevea brasiliensis).
AB  - Rigidoporus microporus (Polyporales, Basidiomycota) syn. Rigidoporus lignosus is
      the most destructive root pathogen of rubber plantations distributed in tropical
      and sub-tropical regions. Our primary objective was to characterize Nigerian
      isolates from rubber tree and compare them with other West African, Southeast
      Asian and American isolates. To characterize the 20 isolates from Nigeria, we
      used sequence data of the nuclear ribosomal DNA ITS and LSU, beta-tubulin and
      translation elongation factor 1-alpha (tef1) gene sequences. Altogether, 40
      isolates of R. microporus were included in the analyses. Isolates from Africa,
      Asia and South/Central America formed three distinctive clades corresponding to
      at least three species. No phylogeographic pattern was detected among R.
      microporus collected from West and Central African rubber plantations suggesting
      continuous gene flow among these populations. Our molecular phylogenetic analysis
      suggests the presence of two distinctive species associated with the white rot
      disease. Phylogenetic analyses placed R. microporus in the Hymenochaetales in the
      vicinity of Oxyporus. This is the first study to characterize R. microporus
      isolates from Nigeria through molecular phylogenetic techniques, and also the
      first to compare isolates from rubber plantations in Africa and Asia. 

PMID- 24863479
TI  - Heterologous expression of a Penicillium purpurogenum pectin lyase in Pichia
      pastoris and its characterization.
AB  - Lignocellulose is the major component of plant cell walls and it represents a
      great source of renewable organic matter. One of lignocellulose constituents is
      pectin. Pectin is composed of two basic structures: a 'smooth' region and a
      'hairy' region. The 'smooth' region (homogalacturonan) is a linear polymer of
      galacturonic acid residues with alpha-(1->4) linkages, substituted by methyl and
      acetyl residues. The 'hairy' region is more complex, containing xylogalacturonan
      and rhamnogalacturonans I and II. Among the enzymes which degrade pectin
      (pectinases) is pectin lyase (E.C. 4.2.2.10). This enzyme acts on highly
      esterified homogalacturonan, catalysing the cleavage of alpha-(1->4) glycosidic
      bonds between methoxylated residues of galacturonic acid by means of beta
      elimination, with the formation of 4,5-unsaturated products. In this work, the
      gene and cDNA of a pectin lyase from Penicillium purpurogenum have been
      sequenced, and the cDNA has been expressed in Pichia pastoris. The gene is 1334
      pb long, has three introns and codes for a protein of 376 amino acid residues.
      The recombinant enzyme was purified to homogeneity and characterized. Pectin
      lyase has a molecular mass of 45 kDa as determined by SDS-PAGE. It is active on
      highly esterified pectin, and decreases 40% the viscosity of pectin with a degree
      of esterification >=85%. The enzyme showed no activity on polygalacturonic acid
      and pectin from citrus fruit 8% esterified. The optimum pH and temperature for
      the recombinant enzyme are 6.0 and 50  degrees C, respectively, and it is stable
      up to 50  degrees C when exposed for 3 h. A purified pectin lyase may be useful
      in biotechnological applications such as the food industry where the liberation
      of toxic methanol in pectin degradation should be avoided.

PMID- 24863480
TI  - Secretome analysis identifies potential virulence factors of Diplodia corticola,
      a fungal pathogen involved in cork oak (Quercus suber) decline.
AB  - The characterisation of the secretome of phytopathogenic fungi may contribute to
      elucidate the molecular mechanisms of pathogenesis. This is particularly relevant
      for Diplodia corticola, a fungal plant pathogen belonging to the family
      Botryosphaeriaceae, whose genome remains unsequenced. This phytopathogenic fungus
      is recognised as one of the most important pathogens of cork oak, being related
      to the decline of cork oak forests in the Iberian Peninsula. Unfortunately,
      secretome analysis of filamentous fungi is limited by the low protein
      concentration and by the presence of many interfering substances, such as
      polysaccharides, which affect the separation and analysis by 1D and 2D gel
      electrophoresis. We compared six protein extraction protocols concerning their
      suitability for further application with proteomic workflows. The protocols
      involving protein precipitation were the most efficient, with emphasis on TCA
      acetone protocol, allowing us to identify the most abundant proteins on the
      secretome of this plant pathogen. Approximately 60% of the spots detected were
      identified, all corresponding to extracellular proteins. Most proteins identified
      were carbohydrate degrading enzymes and proteases that may be related to D.
      corticola pathogenicity. Although the secretome was assessed in a noninfection
      environment, potential virulence factors such as the putative glucan-beta
      glucosidase, neuraminidase, and the putative ferulic acid esterase were
      identified. The data obtained forms a useful basis for a deeper understanding of
      the pathogenicity and infection biology of D. corticola. Moreover, it will
      contribute to the development of proteomics studies on other members of the
      Botryosphaeriaceae.

PMID- 24863481
TI  - Optical clearing agent perfusion enhancement via combination of microneedle
      poration, heating and pneumatic pressure.
AB  - BACKGROUND AND OBJECTIVE: Optical clearing agents (OCAs) have shown promise for
      increasing the penetration depth of biomedical lasers by temporarily decreasing
      optical scattering within the skin. However, their translation to the clinic has
      been constrained by lack of practical means for effectively perfusing OCA within
      target tissues in vivo. The objective of this study was to address this
      limitation through combination of a variety of techniques to enhance OCA
      perfusion, including heating of OCA, microneedling and/or application of
      pneumatic pressure over the skin surface being treated (vacuum and/or positive
      pressure). While some of these techniques have been explored by others
      independently, the current study represents the first to explore their use
      together. STUDY DESIGN/MATERIALS AND METHODS: Propylene glycol (PG) OCA, either
      at room-temperature or heated to 45 degrees C, was topically applied to hydrated,
      body temperature ex vivo porcine skin, in conjunction with various combinations
      of microneedling pre-treatment (0.2 mm length microneedles, performed prior to
      OCA application), vacuum pre-treatment (17-50 kPa, performed prior to OCA
      application), and positive pressure post-treatment (35-172 kPa, performed after
      OCA application). The effectiveness of OCA perfusion was characterized via
      measurements of transmittance, reduced scattering coefficient, and penetration
      depth at a number of medically-relevant laser wavelengths across the visible
      spectrum. RESULTS: Topical application of room-temperature (RT) PG led to an
      increase in transmittance across the visible spectrum of up to 21% relative to
      untreated skin. However, only modest increases were observed with addition of
      various combinations of microneedling pre-treatment, vacuum pre-treatment, and
      positive pressure post-treatment. Conversely, when heated PG was used in
      conjunction with these techniques, we observed significant increases in
      transmittance. Using an optimal PG perfusion enhancement protocol consisting of
      45 degrees C heated PG + microneedle pre-treatment + 35 kPa vacuum pre-treatment
      + 103 kPa positive pressure post-treatment, we observed up to 68% increase in
      transmittance relative to untreated skin, and up to 46% increase relative to
      topical RT PG application alone. Using the optimal PG perfusion enhancement
      protocol, we also observed up to 30% decrease in reduced scattering coefficient
      relative to untreated skin, and up to 20% decrease relative to topical RT PG
      alone. Finally, using the optimal protocol, we observed up to 25% increase in
      penetration depth relative to untreated skin, and up to 23% increase relative to
      topical RT PG alone. CONCLUSIONS: The combination of heated PG, microneedling pre
      treatment, vacuum pre-treatment, and positive pressure-post treatment were
      observed to significantly enhance the perfusion of topically applied PG. Although
      further studies are required to evaluate the efficacy of combined perfusion
      enhancement techniques in vivo, the current results suggest promise for
      facilitating the translation of OCAs to the clinic.

PMID- 24863483
TI  - Fixational saccade-related activity of pedunculopontine tegmental nucleus neurons
      in behaving monkeys.
AB  - Fixational saccades are small, involuntary eye movements that occur during
      attempted visual fixation. Recent studies suggested that several cognitive
      processes affect the occurrence probability of fixational saccades. Thus, there
      might be an interaction between fixational saccade-related motor signals and
      cognitive signals. The pedunculopontine tegmental nucleus (PPTN) in the brainstem
      has anatomical connections with numerous saccade-related and limbic areas.
      Previously, we reported that a group of PPTN neurons showed transient phasic
      bursts or a pause in activity during large visually guided and spontaneous
      saccades, and also showed sustained tonic changes in activity with task context.
      We hypothesised that single PPTN neurons would relay both fixational saccade
      related and task context-related signals, and might function as an interface
      between the motor and limbic systems. We recorded the activity of PPTN neurons in
      behaving monkeys during a reward-biased task, and analysed neuronal activity for
      small fixational saccades during visual fixation, and compared it with the
      activity for large visually guided targeting saccades and large spontaneous
      saccades during intertrial intervals. A population of PPTN neurons exhibited a
      fixational saccade-related phasic increase in activity, and the majority of them
      also showed activity modulation with large targeting saccades. In addition, a
      group of these neurons showed a task-related tonic increase in activity during
      the fixation period, and half of them relayed the saccade signal only when the
      neuron exhibited higher tonic activity during the task execution period. Thus,
      fixational saccade-related signals of PPTN neurons overlap with tonic task
      related signals, and might contribute to the cognitive modulation of fixational
      saccades. 

PMID- 24863482
TI  - Long term differential consequences of miglustat therapy on intestinal
      disaccharidases.
AB  - Miglustat is an oral medication for treatment of lysosomal storage diseases such
      as Gaucher disease type I and Niemann Pick disease type C. In many cases
      application of Miglustat is associated with symptoms similar to those observed in
      intestinal carbohydrate malabsorption. Previously, we have demonstrated that
      intestinal disaccharidases are inhibited immediately by Miglustat in the
      intestinal lumen. Nevertheless, the multiple functions of Miglustat hypothesize
      long term effects of Miglustat on intracellular mechanisms, including
      glycosylation, maturation and trafficking of the intestinal disaccharidases. Our
      data show that a major long term effect of Miglustat is its interference with N
      glycosylation of the proteins in the ER leading to a delay in the trafficking of
      sucrase-isomaltase. Also association with lipid rafts and plausibly apical
      targeting of this protein is partly affected in the presence of Miglustat. More
      drastic is the effect of Miglustat on lactase-phlorizin hydrolase which is
      partially blocked intracellularly. The de novo synthesized SI and LPH in the
      presence of Miglustat show reduced functional efficiencies according to altered
      posttranslational processing of these proteins. However, at physiological
      concentrations of Miglustat (<=50 MUM) a major part of the activity of these
      disaccharidases is found to be still preserved, which puts the charge of the
      observed carbohydrate maldigestion mostly on the direct inhibition of
      disaccharidases in the intestinal lumen by Miglustat as the immediate side
      effect. 

PMID- 24863484
TI  - Lack of formyl peptide receptor 1 and 2 leads to more severe inflammation and
      higher mortality in mice with of pneumococcal meningitis.
AB  - Bacterial meningitis is, despite progress in research and the development of new
      treatment strategies, still a cause of severe neuronal sequelae. The brain is
      protected from penetrating pathogens by both the blood-brain barrier and the
      innate immune system. The invading pathogens are recognized by pattern
      recognition receptors including the G-protein coupled formyl peptide receptors
      (FPRs), which are expressed by immune cells of the central nervous system. The
      expression of FPRs is up-regulated during bacterial meningitis, but the
      consequence on the progression of inflammation and impact on mortality are far
      from clear. Therefore, we used mFPR1 and mFPR2-deficient mice to investigate the
      effects on inflammation, bacterial growth and mortality in a mouse model of
      pneumococcal meningitis. Our results revealed increased bacterial burden,
      increased neutrophil infiltration and higher mortality in mFPR1/2-deficient mice
      in comparison to wild-type mice. The mFPR1- or mFPR2-deficient mice also showed
      significantly increased glial cell density, whereas the immune responses
      including the expression of anti-inflammatory cytokines and antimicrobial
      peptides were decreased in bacterial meningitis. Taken together, the results
      suggest that FPR1 and FPR2 play an important role in the innate immune responses
      against Streptococcus pneumoniae within the central nervous system and the lack
      of the receptors leads to a dysregulation of the inflammatory response compared
      with wild-type mice. 

PMID- 24863487
TI  - Immunization of healthcare providers: a critical step toward patient safety.

PMID- 24863486
TI  - The impact of pre-existing antibody on subsequent immune responses to
      meningococcal A-containing vaccines.
AB  - Major epidemics of serogroup A meningococcal meningitis continue to affect the
      African meningitis belt. The development of an affordable conjugate vaccine
      against the disease became a priority for World Health Organization (WHO) in the
      late 1990s. Licensing of meningococcal vaccines has been based on serological
      correlates of protection alone, but such correlates might differ in different
      geographical regions. If high pre-vaccination antibody concentrations/titers
      impacts on the response to vaccination and possibly vaccine efficacy, is not
      clearly understood. We set out to define the pre-vaccination Meningococcal group
      A (Men A) antibody concentrations/titers in The Gambia and study their impact on
      the immunogenicity of Men A containing vaccines. Data from subjects originally
      enrolled in studies to test the safety and immunogenicity of the MenA vaccine
      recently developed for Africa meningococcal A polysaccharide conjugated to
      tetanus toxoid, MenAfriVac((r)) (PsA-TT) were analyzed. Participants had been
      randomized to receive either the study vaccine PsA-TT or the reference
      quadrivalent plain polysaccharide vaccine containing meningococcal groups A, C,
      W, and Y, Mencevax((r)) ACWY, GlaxoSmithKline (PsACWY) in a 2:1 ratio. Venous
      blood samples were collected before and 28 days after vaccination. Antibodies
      were assayed by enzyme-linked immunosorbent assay (ELISA) for geometric mean
      concentrations and serum bactericidal antibody (SBA) for functional antibody. The
      inter age group differences were compared using ANOVA and the pre and post
      vaccination differences by t test. Over 80% of the >=19 year olds had pre
      vaccination antibody concentrations above putatively protective concentrations as
      compared to only 10% of 1-2 year olds. Ninety-five percent of those who received
      the study vaccine had >=4-fold antibody responses if they had low pre-vaccination
      concentrations compared to 76% of those with high pre-vaccination concentrations.
      All subjects with low pre-vaccination titers attained >=4-fold responses as
      compared to 76% with high titers where study vaccine was received. Our data
      confirm the presence of high pre-vaccination Men A antibody concentrations/titers
      within the African meningitis belt, with significantly higher concentrations in
      older individuals. Although all participants had significant increase in antibody
      levels following vaccination, the four-fold or greater response in antibody
      titers were significantly higher in individuals with lower pre-existing antibody
      titers, especially after receiving PsA-TT. This finding may have some
      implications for vaccination strategies adopted in the future. 

PMID- 24863485
TI  - Early repolarization increases the occurrence of sustained ventricular
      tachyarrhythmias and sudden death in the chronic phase of an acute myocardial
      infarction.
AB  - BACKGROUND: We recently showed that the presence of early repolarization (ER)
      increases the risk of ventricular fibrillation occurrences in the early phase of
      acute myocardial infarction (AMI). This study aimed to clarify whether an
      association exists between ER and occurrences of ventricular tachyarrhythmias or
      sudden death in the chronic phase of AMI. METHODS AND RESULTS: This study
      retrospectively enrolled 1131 patients (67+/-12 years; 862 men) with AMIs
      surviving 14 days post-AMI. The primary end point was the occurrence of sustained
      ventricular tachyarrhythmias or sudden death >14 days after the AMI onset. We
      evaluated the presence of ER from the predischarge ECG (mean 10+/-3 days post
      AMI). ER was defined as an elevation of the terminal portion of the QRS complex
      of >0.1 mV in inferior or lateral leads. After a median follow-up of 26.2 months,
      26 patients had an episode of ventricular tachyarrhythmias or sudden death. A
      multivariable Cox regression analysis revealed the presence of ER (hazard ratio,
      5.37; 95% confidence interval, 2.27-12.69; P<0.001), Killip class on admission of
      >I (hazard ratio, 2.75; 95% confidence interval, 1.24-6.07; P=0.013), and a left
      ventricular ejection fraction of <35% (hazard ratio, 11.83; 95% confidence
      interval, 5.16-27.13; P<0.001) were significantly associated with event
      occurrences. As features of the ER pattern, ER in the inferior leads, high
      amplitude ER, a notched morphology, and ER without ST-segment elevation were
      associated with an increased risk of event occurrences. CONCLUSIONS: ER observed
      at a mean of 10 days post-AMI may be a marker for a subsequent risk of
      ventricular tachyarrhythmias or sudden death.

PMID- 24863488
TI  - Variation in cyanogenic glycosides across populations of wild lima beans
      (Phaseolus lunatus) has no apparent effect on bruchid beetle performance.
AB  - Cyanogenic glycosides (CNGs) act as feeding or oviposition deterrents and are
      toxic after enzymatic hydrolysis, thus negatively affecting herbivore
      performance. While most studies on CNGs focus on leaf herbivores, here we
      examined seeds from natural populations of Phaseolus lunatus in Mexico. The
      predominant CNGs, linamarin and lotaustralin, were quantified for each population
      by using ultra-high pressure liquid chromatography-mass spectrometry. We also
      examined whether there was a correlation between the concentration of CNGs and
      the performance of the Mexican bean beetle, Zabrotes subfasciatus, on seeds from
      each population(.) The concentrations of CNGs in the seeds were relatively high
      compared to the leaves and were significantly variable among populations.
      Surprisingly, this had little effect on the performance of the bruchid beetles.
      Zabrotes subfasciatus can tolerate high concentrations of CNGs, most likely
      because of the limited beta-glucosidase activity in the seeds. Seed herbivory
      does not appear to liberate hydrogen cyanide due to the low water content in the
      seed. This study illustrates the importance of quantifying the natural variation
      and activity of toxic compounds in order to make relevant biological inferences
      about their role in defense against herbivores. 

PMID- 24863489
TI  - Glycoalkaloids of wild and cultivated Solanum: effects on specialist and
      generalist insect herbivores.
AB  - Plant domestication by selective breeding may reduce plant chemical defense in
      favor of growth. However, few studies have simultaneously studied the defensive
      chemistry of cultivated plants and their wild congeners in connection to
      herbivore susceptibility. We compared the constitutive glycoalkaloids (GAs) of
      cultivated potato, Solanum tuberosum, and a wild congener, S. commersonii, by
      liquid chromatography coupled to mass spectrometry. We also determined the major
      herbivores present on the two species in field plots, and tested their preference
      for the plants and their isolated GAs in two-choice bioassays. Solanum
      commersonii had a different GA profile and higher concentrations than S.
      tuberosum. In the field, S. tuberosum was mostly attacked by the generalist
      aphids Myzus persicae and Macrosiphum euphorbiae, and by the specialist flea
      beetle Epitrix argentinensis. In contrast, the most common herbivore on S.
      commersonii was the specialist sawfly Tequus sp. Defoliation levels were higher
      on the wild species, probably due to the chewing feeding behavior of Tequus sp.
      As seen in the field, M. persicae and E. argentinensis preferred leaf disks of
      the cultivated plant, while Tequus sp. preferred those of the wild one.
      Congruently, GAs from S. commersonii were avoided by M. persicae and preferred by
      Tequus sp. The potato aphid performed well on both species and was not deterred
      by S. commersonii GAs. These observations suggest that different GA profiles
      explain the feeding preferences of the different herbivores, and that
      domestication has altered the defensive capacity of S. tuberosum. However, the
      wild relative is still subject to severe defoliation by a specialist herbivore
      that may cue on the GAs. 

PMID- 24863491
TI  - Structural comparison of lipophosphoglycan from Leishmania turanica and L. major,
      two species transmitted by Phlebotomus papatasi.
AB  - The lipophosphoglycan (LPG) of Leishmania major has a major role in the
      attachment to Phlebotomus papatasi midgut. Here, we investigated the comparative
      structural features of LPG of L. turanica, another species transmitted by P.
      papatasi. The mAb WIC 79.3, specific for terminal Gal(beta1,3) side-chains,
      strongly reacted with L. turanica LPG. In contrast, L. turanica LPG was not
      recognized by arabinose-specific mAb 3F12. In conclusion, LPGs from L. major and
      L. turanica are similar, with the latter being less arabinosylated than L.
      major's. The high galactose content in L. turanica LPG is consistent with its
      predicted recognition by P. papatasi lectin PpGalec. 

PMID- 24863490
TI  - Specificity of herbivore-induced hormonal signaling and defensive traits in five
      closely related milkweeds (Asclepias spp.).
AB  - Despite the recognition that phytohormonal signaling mediates induced responses
      to herbivory, we still have little understanding of how such signaling varies
      among closely related species and may generate herbivore-specific induced
      responses. We studied closely related milkweeds (Asclepias) to link: 1) plant
      damage by two specialist chewing herbivores (milkweed leaf beetles Labidomera
      clivicolis and monarch caterpillars Danaus plexippus); 2) production of the
      phytohormones jasmonic acid (JA), salicylic acid (SA), and abscisic acid (ABA);
      3) induction of defensive cardenolides and latex; and 4) impacts on Danaus
      caterpillars. We first show that A. syriaca exhibits induced resistance following
      monarch herbivory (i.e., reduced monarch growth on previously damaged plants),
      while the defensively dissimilar A. tuberosa does not. We next worked with a
      broader group of five Asclepias, including these two species, that are highly
      divergent in defensive traits yet from the same clade. Three of the five species
      showed herbivore-induced changes in cardenolides, while induced latex was found
      in four species. Among the phytohormones, JA and ABA showed specific responses
      (although they generally increased) to insect species and among the plant
      species. In contrast, SA responses were consistent among plant and herbivore
      species, showing a decline following herbivore attack. Jasmonic acid showed a
      positive quantitative relationship only with latex, and this was strongest in
      plants damaged by D. plexippus. Although phytohormones showed qualitative
      tradeoffs (i.e., treatments that enhanced JA reduced SA), the few significant
      individual plant-level correlations among hormones were positive, and these were
      strongest between JA and ABA in monarch damaged plants. We conclude that: 1)
      latex exudation is positively associated with endogenous JA levels, even among
      low-latex species; 2) correlations among milkweed hormones are generally
      positive, although herbivore damage induces a divergence (tradeoff) between JA
      and SA; 3) induction of cardenolides and latex are not necessarily
      physiologically linked; and 4) even very closely related species show highly
      divergent induction, with some species showing strong defenses, hormonally
      mediated induction, and impacts on herbivores, while other milkweed species
      apparently use alternative strategies to cope with insect attack. 

PMID- 24863492
TI  - Radical-driven peptide backbone dissociation tandem mass spectrometry.
AB  - In recent years, a number of novel tandem mass spectrometry approaches utilizing
      radical-driven peptide gas-phase fragmentation chemistry have been developed.
      These approaches show a peptide fragmentation pattern quite different from that
      of collision-induced dissociation (CID). The peptide fragmentation features of
      these approaches share some in common with electron capture dissociation (ECD) or
      electron transfer dissociation (ETD) without the use of sophisticated equipment
      such as a Fourier-transform mass spectrometer. For example, Siu and coworkers
      showed that CID of transition metal (ligand)-peptide ternary complexes led to the
      formation of peptide radical ions through dissociative electron transfer (Chu et
      al., 2000. J Phys Chem B 104:3393-3397). The subsequent collisional activation of
      the generated radical ions resulted in a number of characteristic product ions,
      including a, c, x, z-type fragments and notable side-chain losses. Another
      example is the free radical initiated peptide sequencing (FRIPS) approach, in
      which Porter et al. and Beauchamp et al. independently introduced a free radical
      initiator to the primary amine group of the lysine side chain or N-terminus of
      peptides (Masterson et al., 2004. J Am Chem Soc 126:720-721; Hodyss et al., 2005
      J Am Chem Soc 127: 12436-12437). Photodetachment of gaseous multiply charged
      peptide anions (Joly et al., 2008. J Am Chem Soc 130:13832-13833) and UV
      photodissociation of photolabile radical precursors including a C-I bond (Ly &
      Julian, 2008. J Am Chem Soc 130:351-358; Ly & Julian, 2009. J Am Soc Mass
      Spectrom 20:1148-1158) also provide another route to generate radical ions. In
      this review, we provide a brief summary of recent results obtained through the
      radical-driven peptide backbone dissociation tandem mass spectrometry approach.

PMID- 24863493
TI  - Polytypism in superhard transition-metal triborides.
AB  - The quest of novel compounds with special structures and unusual functionalities
      continues to be a central challenge to modern materials science. Even though
      their exact structures have puzzled scientists for decades, superhard transition
      metal borides (TMBs) have long been believed to exist only in simple crystal
      structures. Here, we report on a polytypic phenomenon in superhard WB3 and MoB3
      with a series of energetically degenerate structures due to the random stacking
      of metal layers amongst the interlocking boron layers. Such polytypism can create
      a multiphase solid-solution compound with a large number of interfaces amongst
      different polytypes, and these interfaces will strongly hinder the interlayer
      sliding movement within each polytype, thereby further increase the hardness of
      this particular material. Furthermore, in contrast to the conventional knowledge
      that intrinsically strong chemical bonds in superhard materials should lead to
      high lattice thermal conductivity, the polytypic TMB3 manifest anomalously low
      lattice thermal conductivity due to structural disorders and phonon folding.
      These findings promise to open a new avenue to searching for novel superhard
      materials with additional functionalities. 

PMID- 24863494
TI  - X-linked Charcot-Marie-Tooth type 1: stroke-like presentation of a novel GJB1
      mutation.
AB  - X-linked Charcot-Marie-Tooth type 1 (CMTX1) is the second most common type of CMT
      and is caused by mutations in the Gap-Junction Beta-1 gene (GJB1), encoding
      connexin 32 which is expressed in Schwann cells as well as in oligodendrocytes.
      More than 400 GJB1 mutations have been described to date. Many mutation-carrier
      males have subclinical central nervous system (CNS) involvement, a few show mild
      CNS clinical signs, whereas only rarely overt though transient CNS dysfunction
      occurs. We report a 29-year-old man with CMTX1 who, at 16 years, showed short
      lived CNS symptoms with transitory white matter abnormalities on cerebral
      magnetic resonance imaging (MRI) as first clinical presentation of a novel GJB1
      mutation (p.Gln99_His100insGln). He had three consecutive episodes of right
      hemiparesis, together with sensory loss in the paretic limbs and expressive
      aphasia, all lasting a few hours, over a 2-day period, with concurrent white
      matter hyperintensity on MRI. These "stroke-like" episodes occurred just after
      arriving at sea level, after travelling from home at 700 m of altitude. Only a
      few years later did symptoms of peripheral neuropathy appear. In conclusion,
      CMTX1 should be included in the differential diagnosis of diseases characterized
      by transient CNS symptoms and white matter abnormalities on MRI.

PMID- 24863495
TI  - The last months of life of people with amyotrophic lateral sclerosis in
      mechanical invasive ventilation: a qualitative study.
AB  - In Italy 10-30% of patients who die with amyotrophic lateral sclerosis are
      invasively ventilated. It is difficult to predict when patients will die and when
      a specialist palliative care service may effectively be involved. Nineteen semi
      structured interviews with informal family carers who looked after these patients
      who had died in last 10 years were undertaken to ascertain their experiences in
      the final stages of the disease. The mean survival after tracheostomy was 30
      months (median 24 months). Fifty-eight percent of the patients had not wanted to
      be tracheostomized before the procedure, but often felt pressured into the
      decision to have a tracheostomy. Following the procedure the individual quality
      of life decreased for many patients and carers. In last 4-6 months both carers
      and patients were aware of a clear deterioration and reported cognitive
      communication impairment, local infections and sepsis, pressure sores, the need
      for indwelling catheters and the use of sedative-analgesic drugs. The study shows
      that tracheostomy is often undertaken with little discussion. The end-of-life
      phase can be defined, with several indicators of deterioration, which could be
      triggers for the involvement of palliative care.

PMID- 24863496
TI  - Antimicrobial consumption and resistance in five Gram-negative bacterial species
      in a hospital from 2003 to 2011.
AB  - BACKGROUND: The misuse of antimicrobial agents increases drug resistance in
      bacteria. METHODS: The correlation between antimicrobial agent consumption and
      related resistance in the Gram-negative bacteria Acinetobacter baumannii,
      Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Proteus
      mirabilis was analyzed during the period 2003-2011. RESULTS: Among these five
      bacteria, overall E. coli and K. pneumoniae were more commonly isolated from
      bloodstream than the other species. Regarding Enterobacteriaceae, E. coli and K.
      pneumoniae showed annual increases of resistance to the tested antimicrobial
      agents; conversely, P. mirabilis exhibited reduced resistance to cefuroxime,
      ceftriaxone and cefepime. In contrast to the relatively low antimicrobial
      resistance in P. aeruginosa, A. baumannii revealed high resistance, which was
      over 85% resistant rate to the tested antimicrobial agents and over 80%
      carbapenem resistance in 2011. E. coli, K. pneumoniae, and P. mirabilis differed
      in development of antimicrobial resistance after consumption of the antimicrobial
      agents. K. pneumoniae developed resistance to all antimicrobial groups, whereas
      resistance in P. mirabilis was not related to any antimicrobial consumption. P.
      aeruginosa developed resistance to beta-lactam antimicrobials and
      aminoglycosides, whereas A. baumanii developed resistance to carbapenems after
      their use. CONCLUSION: The development of antimicrobial resistance was related to
      antimicrobial agents and bacterial species.

PMID- 24863497
TI  - Recombinant tuberculosis vaccine AEC/BC02 induces antigen-specific cellular
      responses in mice and protects guinea pigs in a model of latent infection.
AB  - PURPOSE: To preliminarily evaluate the immunogenicity and efficacy of the
      recombinant tuberculosis vaccine AEC/BC02 in which Ag85b and fusion protein ESAT6
      CFP10 were combined with bacillus Calmette-Guerin CpG and an aluminum salt-based
      adjuvant system. METHODS: Groups of BALB/c mice were immunized intramuscularly
      three times at 10-day intervals with AEC/BC02 or the adjuvant alone and the
      vaccine-induced cell-mediated immune responses were evaluated. The efficacy of
      AEC/BC02 was evaluated in two guinea pig models, one a model of prevention and
      the other a model of latent infection. RESULTS: The AEC/BC02 vaccine induced
      strong cellular immune responses characterized by a high frequency of antigen
      specific interferon-gamma-secreting T cells in mice at different time points
      after the last vaccination. In the preventive model of guinea pig, AEC/BC02 did
      not protect against Mycobacterium tuberculosis as a pre-exposure vaccine.
      However, in a latent infection model of guinea pig, it effectively controlled the
      reactivation of M. tuberculosis and lowered the bacterial load in the lung and
      spleen. CONCLUSION: These results indicate AEC/BC02 can protect against
      reactivation of latent infection and may function as a therapeutic vaccine.

PMID- 24863498
TI  - Demography and burden of care associated with patients readmitted for urinary
      tract infection.
AB  - BACKGROUND: Urinary tract infection (UTI) is one of the most prevalent admission
      diagnoses in hospital-based clinical practice. Despite its frequency, few data
      are available regarding its demographics and economic implications. PURPOSE: To
      describe the demography, epidemiology, and burden of care of patients admitted to
      hospital with UTI and compare these characteristics depending on admission
      status. METHODS: A retrospective cohort study using an administrative database of
      patients admitted to Hartford Hospital (September 2011-August 2012) with UTI.
      Patient demographics, hospital characteristics, and total costs of care were
      examined. RESULTS: A total of 2345 unique patients were included. The mean age of
      the patients was 78 years and 71% were female. Median length of stay and total
      cost were 5 days and $8326 (interquartile range $5388-$14,179), respectively. A
      total of 359 patients (16.4%) were readmitted within 30 days, of which 111
      patients (5.1%) had UTI on readmission. Only 16.3% of readmitted patients were
      infected with the same causative pathogen. A significant increase in the
      incidence of Enterococcus faecalis (1.2% vs. 9.3%; p = 0.046) occurred upon
      readmission, whereas occurrence of Enterobacteriaceae infection decreased in the
      readmission group (50.0% vs. 25.6%; p = 0.006), including a lower proportion of
      Escherichia coli (32.5% vs. 11.6%; p < 0.001). A higher proportion of readmission
      pathogens were nonsusceptible, including significant changes to cefazolin (24.4%
      vs. 63.6%; p = 0.004) and cefepime (8.7% vs. 27.6; p = 0.05). CONCLUSION: UTI is
      highly prevalent and is associated with significant utilization of health-care
      resources among hospitalized patients. These findings, coupled with considerable
      rates of 30-day readmission, stress the importance of proper diagnosis and
      treatment.

PMID- 24863499
TI  - Clonal dissemination of extensively drug-resistant Acinetobacter baumannii
      producing an OXA-23 beta-lactamase at a teaching hospital in Shanghai, China.
AB  - BACKGROUND/PURPOSE: Extensively drug-resistant (XDR) Acinetobacter baumannii
      presents a serious therapeutic and infection control challenge. This study aimed
      to explore the causes for the rapid increase of XDR A. baumannii at a teaching
      hospital in Shanghai. METHODS: All consecutive clinical isolates of XDR A.
      baumannii were collected from January to December 2010 at Huashan Hospital in
      Shanghai. The prevalence of carbapenemase genes was investigated by polymerase
      chain reaction (PCR) amplification. Genetic relatedness of the isolates was
      determined by enterobacterial repetitive intergenic consensus-PCR and multilocus
      sequence typing. A retrospective case-control study was performed for the
      identification of risk factors of XDR A. baumannii infections. RESULTS: All 106
      XDR A. baumannii isolates carried the blaOxA-23 gene and were resistant to all
      antimicrobial agents tested, except colistin, tigecycline and cefoperazone
      sulbactam. One hundred and five of the strains belonged to clonal complex 92 by
      multilocus sequence typing, and 78 were classified as clone A1 by enterobacterial
      repetitive intergenic consensus-PCR. Intensive care unit residency at the time of
      isolation, recent general anesthesia, the number of previous antibiotic classes
      administered and previous hospitalization were identified as risk factors by case
      control study. Efficacy rates were 62.5% (5/8), 47.4% (9/19), and 42.9% (3/7)
      when the XDR patients were treated with cefoperazone-sulbactam, carbapenems, or
      both cefoperazone-sulbactam and carbapenem, alone or in combination with other
      agents, respectively. CONCLUSION: XDR A. baumannii producing OXA-23 beta
      lactamase was clonally disseminated at a university hospital in Shanghai.
      Cefoperazone-sulbactam and carbapenems alone or combined with other antibiotics
      may benefit XDR A. baumannii infections in the absence of other effective
      antibiotics.

PMID- 24863501
TI  - Extremely fast gas/liquid reactions in flow microreactors: carboxylation of short
      lived organolithiums.
AB  - Carboxylation of short-lived organolithiums bearing electrophilic functional
      groups such as nitro, cyano, and alkoxycarbonyl groups with CO2 to give
      carboxylic acids and active esters was accomplished in a flow microreactor
      system. The successful reactions indicate that gas/liquid mass transfer and the
      subsequent chemical reaction with CO2 are extremely fast. 

PMID- 24863500
TI  - Quantification and genetic analysis of salivirus/klassevirus in wastewater in
      Arizona, USA.
AB  - Salivirus/klassevirus sequences were identified in 7 (15%) wastewater samples
      collected in Arizona monthly for a year, with the highest concentration of 2.28 *
      10(5) and 2.46 * 10(4) copies/L in influent and effluent, respectively. This is
      the first report of quantification and genetic analysis of salivirus/klassevirus
      in water samples in the United States.

PMID- 24863502
TI  - Factors influencing the accuracy of fetal weight estimation with a focus on
      preterm birth at the limit of viability: a systematic literature review.
AB  - BACKGROUND: Fetal weight estimation (FWE) is an important factor for clinical
      management decisions, especially in imminent preterm birth at the limit of
      viability between 23(0/7) and 26(0/7) weeks of gestation. It is crucial to detect
      and eliminate factors that have a negative impact on the accuracy of FWE. DATA
      SOURCES: In this systematic literature review, we investigated 14 factors that
      may influence the accuracy of FWE, in particular in preterm neonates born at the
      limit of viability. RESULTS: We found that gestational age, maternal body mass
      index, amniotic fluid index and ruptured membranes, presentation of the fetus,
      location of the placenta and the presence of multiple fetuses do not seem to have
      an impact on FWE accuracy. The influence of the examiner's grade of experience
      and that of fetal gender were discussed controversially. Fetal weight, time
      interval between estimation and delivery and the use of different formulas seem
      to have an evident effect on FWE accuracy. No results were obtained on the impact
      of active labor. DISCUSSION: This review reveals that only few studies
      investigated factors possibly influencing the accuracy of FWE in preterm neonates
      at the limit of viability. Further research in this specific age group on
      potential confounding factors is needed.

PMID- 24863504
TI  - Summaries for patients. Screening for hepatitis B virus infection: U.S.
      Preventive Services Task Force recommendation statement.

PMID- 24863503
TI  - Biochemical characterization of the tandem HAMP domain from Natronomonas
      pharaonis as an intraprotein signal transducer.
AB  - Available structures of HAMP domains suggest rotation as one potential mechanism
      in intraprotein signal transduction. It has been proposed that in poly-HAMP
      modules the signal sign is inverted with each additional HAMP. We examined signal
      transduction through the HAMP tandem domain from the phototaxis transducer of the
      halophilic archaeon Natronomonas pharaonis in membrane-bound chimeras consisting
      of the Escherichia coli chemotaxis receptor for serine, Tsr, as an input and the
      mycobacterial adenylyl cyclase Rv3645 as an output domain, i.e. the basic chimera
      was 'Tsr-NpHAMP tandem-Rv3645 cyclase'. Neither of the NpHAMP units alone nor the
      NpHAMP tandem transduced a serine signal. After five targeted point mutations in
      the first alpha-helix of NpHAMP1 , the non-functional NpHAMP modules combined
      into a functional HAMP tandem. 1 mm serine significantly inhibited cyclase
      activity (-35%; IC50  = 30 MUm) in disagreement with the structure-based
      predictions. Surprisingly, replacement of NpAS11 in the tandem by the respective
      AS1 from HAMPT sr resulted in signal inversion, i.e. serine activated cyclase
      (+129%; EC50  = 10 MUm). Examination of 48 mutants of AS11 in the HAMP tandem
      including two residues of a putative N-terminal control cable identified five
      residues in NpAS11 which probably define different ground states of the output
      domain and thus affect the sign of signal output. The data question the predicted
      HAMP rotation as the predominant mechanism of intraprotein signal transduction
      and point to as yet unrecognized conformational motions of HAMP domains in
      intraprotein signaling. 

PMID- 24863505
TI  - Neurocysticercosis: still some unanswered questions.

PMID- 24863506
TI  - Complex visual hallucinations in mentally healthy people.

PMID- 24863507
TI  - Charles Bonnet syndrome: characteristics of its visual hallucinations and
      differential diagnosis.
AB  - OBJECTIVE: To present an eight-case serie of patients with Charles Bonnet
      syndrome (CBS). METHOD: All patients were initially evaluated by an
      ophthalmologist and then submitted to a neurologic evaluation with exclusion of
      alternative psychiatric and neurologic diagnoses. RESULTS: Five patients were
      male (62.5%) and the mean age was 52.3+16.0 years. Two patients suffered from
      severe myopia and glaucoma, three had retinitis pigmentosa, one had anterior
      ischemic optic neuropathy, one had age-related macular degeneration and one had
      toxoplasmic retinochoroiditis. Mean visual acuity in the right eye was 1,12
      logMAR and in the left eye 0.57 logMAR. A mean delay of 41.7 months occurred
      until diagnosis. All hallucinations were complexes and mostly ocurred on a weekly
      basis (62.5%) and lasted for seconds (87.5%). CONCLUSIONS: Physicians who care
      for low vision patients should be aware of CBS and appropriately diagnose its
      hallucinations after exclusion of psychiatric and neurologic diseases.

PMID- 24863509
TI  - The relationship between sleep quality, depression, and anxiety in patients with
      epilepsy and suicidal ideation.
AB  - The relationships among suicidal ideation, sleep, depression, anxiety, and
      effects on epilepsy require more research. OBJECTIVE: The aim of this study was
      to estimate the prevalence of suicidal ideation in outpatients with epilepsy, and
      relate this to sleep quality, daytime sleepiness, depression, and anxiety.
      METHOD: Ninety-eight non-selected patients were evaluated. The subjects were
      classified as "suicidal ideators" or "non-ideators", based on their response to
      item 9 of the Beck Depression Inventory. RESULTS: The prevalence of suicidal
      ideation was 13.3% (chi2=50.46, p<0.001). The differences between cases with or
      without suicidal ideation were statistically significant in relation to sleep
      quality (p=0.005) and symptoms of depression (p=0.001) and anxiety (p=0.002).
      CONCLUSION: Our results revealed that depression and anxiety were associated with
      sleep quality, daytime sleepiness, and suicidal ideation and that depression and
      sleep disturbance were good predictors of suicide in subjects with epilepsy.

PMID- 24863508
TI  - ENCOMS: Argentinian survey in cost of illness and unmet needs in multiple
      sclerosis.
AB  - The objective of the study was to assess the cost of multiple sclerosis (MS)
      patients in Argentina categorized by disease severity using a societal
      perspective. METHOD: Cross-sectional study including MS patients from 21 MS
      centers in 12 cities of Argentina. Patients were stratified by disease severity
      using the expanded disability status scale (EDSS) (group 1 with EDSS score
      between 0 and 3; group 2 with EDSS >3 and <7; group 3 with EDSS >=7). Direct and
      indirect costs were analyzed for the second quarter of 2012 from public sources
      and converted to US Dollars. RESULTS: 266 patients were included. Mean annual
      cost per MS patient was USD 36,025 (95%CI 31,985-38,068) for patients with an
      EDSS between 0-3; USD 40,705 (95%CI 37,199-46,300) for patients with EDSS >3 and
      <7, and USD 50,712 (95%CI 47,825-62,104) for patients with EDSS >=7. CONCLUSIONS:
      This is the first Argentine study evaluating the costs of MS considering disease
      severity.

PMID- 24863510
TI  - Fluency in Parkinson's disease: disease duration, cognitive status and age.
AB  - The objective of this study was to determine the frequency of occurrence and to
      characterize the typology of dysfluencies in individuals with Parkinson's disease
      (PD), including the variables age, gender, schooling, disease duration, score on
      the Hoehn and Yahr scale and cognitive status (score on Mini-Mental State
      Examination). A cross-sectional study of a sample comprising 60 adults matched
      for gender, age and schooling was conducted. Group I comprised 30 adults with
      idiopathic PD, and Group II comprised 30 healthy adults. For assessment of
      fluency of speech, subjects were asked to utter a narrative based on a sequence
      of drawings and a transcription of 200 fluent syllables was performed to identify
      speech dysfluencies. PD patients exhibited a higher overall number of
      dysfluencies in speech with a large number of atypical dysfluencies.
      Additionally, results showed an influence of the variables cognitive status,
      disease duration and age on occurrence of dysfluencies. 

PMID- 24863512
TI  - Side-to-side growth discrepancies in children with hemiplegic cerebral palsy:
      association with function, activity and social participation.
AB  - OBJECTIVE: Evaluate side-to-side discrepancies in children with hemiplegic
      cerebral palsy (HCP), and investigate associations of these discrepancies with
      patients' age at initiation of physical therapy, motor and cognitive function,
      and degree of activities and social participation. METHOD: We obtained eight side
      to-side measurements from 24 HCP children with mean age 49.3+/-5.2 months.
      RESULTS: Early initiation of physical therapy was associated with lower
      discrepancy in hand length (p=0.037). Lower foot length discrepancy was
      associated with lower requirement for caregiver assistance in activities related
      to mobility. Increased side-to-side discrepancy was associated with reduced wrist
      extension and increased spasticity. Discrepancy played a larger role in children
      with hemineglect and in those with right involvement. CONCLUSION: Increased
      discrepancy in HCP children was associated with reduced degree of activity/social
      participation. These results suggest an association between functional use of the
      extremities and limb growth.

PMID- 24863511
TI  - Frequency of the LRRK2 G2019S mutation in late-onset sporadic patients with
      Parkinson's disease.
AB  - Mutations in the LRRK2 gene, predominantly G2019S, have been reported in
      individuals with autosomal dominant inheritance and sporadic Parkinson's disease
      (PD). The G2019S mutation has an age-dependent penetrance and evidence shows
      common ancestry. The clinical manifestations are indistinguishable from
      idiopathic PD. Its prevalence varies according to the population studied ranging
      from less than 0.1% in Asians to 41% in North African Arabs. This study aimed to
      identify G2019S mutation in Brazilian idiopathic PD patients. METHOD: We sampled
      100 PD patients and 100 age- and gender-matched controls. Genetical analysis was
      accomplished by polymerase chain reaction (PCR). RESULTS: No G2019S mutations
      were found in both patients with sporadic PD and controls. CONCLUSIONS: Our
      results may be explained by the relatively small sample size.

PMID- 24863513
TI  - Treatment of ischemic stroke with r-tPA: implementation challenges in a tertiary
      hospital in Brazil.
AB  - PURPOSE: This paper presents the initial experience with thrombolysis for acute
      ischaemic stroke at Hospital de Base do Distrito Federal (HBDF), Brazil, and the
      difficulties associated with the implementation of this treatment. METHOD: A
      retrospective study was performed using the medical records of all patients with
      acute stroke who were treated with intravenous alteplase in our department,
      between May 2011 and April 2012. RESULTS: The thrombolytic therapy was
      administered to 32 patients. The mean time between the ictus and the start of
      stroke therapy start was 195 (60-270) minutes. Sixteen patients demonstrated a
      significant clinical improvement (decrease in National Institute Health Stroke
      Scale [NIHSS] score>=4 points in 24 hours); 6 patients were discharged with an
      NIHSS score of 0 and 2 demonstrated haemorrhagic transformation. CONCLUSIONS: The
      results of our study are similar to those reported in the literature, although we
      have been dealing with difficulties, such as the lack of a stroke unit.

PMID- 24863514
TI  - Conversive gait disorder: you cannot miss this diagnosis.
AB  - Bizarre, purposeless movements and inconsistent findings are typical of
      conversive gaits. The objective of the present paper is to review some
      phenomenological aspects of twenty-five consecutive conversive gait disorder
      patients. Some variants are typical - knees give way-and-recover presentation,
      monoparetic, tremulous, and slow motion - allowing clinical diagnosis with high
      precision. 

PMID- 24863515
TI  - Endoscopic transnasal approach for removing pituitary tumors.
AB  - To describe a series of 129 consecutive patients submitted to the resection of
      pituitary tumors using the endoscopic transsphenoidal approach in a public
      medical center. METHOD: Retrospective analysis based on the records of patients
      submitted to the resection of a pituitary tumor through the endoscopic
      transsphenoidal approach between 2004 and 2009. RESULTS: One hundred and twenty
      nine records were analyzed. The tumor was non-secreting in 96 (74.42%) and
      secreting in 33 patients (22.58%). Out of the secretory tumors, the most
      prevalent was the growth hormone producer (7.65%), followed by the prolactinoma,
      (6.98%). Eleven patients developed cerebral spinal fluid (CSF) fistulas, and four
      of them developed meningitis. One patient died due to intracerebral hemorrhage in
      the postoperative period. CONCLUSION: The endoscopic transsphenoidal approach to
      sellar tumors proved to be safe when the majority of the tumors were non
      secreting. The most frequent complication was CSF. This technique can be done
      even in a public hospital with financial limits, since the health professionals
      are integrated.

PMID- 24863516
TI  - The relationship between neurocysticercosis and epilepsy: an endless debate.
AB  - Neurocysticercosis (NC), or cerebral infection with Taenia solium, is an
      important public health problem worldwide. Among the neurological sequelae of NC,
      seizures have been described as the most common symptom. Acute symptomatic
      seizures often result from degeneration of a viable cyst; however, not all of
      these patients with acute or provoked seizures will develop epilepsy (i.e.,
      recurrent unprovoked seizures). Because of the high prevalence of epilepsy and
      NC, a causal, as well as incidental relationship between the two may exist. The
      epileptogenicity of calcified cysts as well as the potential association between
      NC and hippocampal sclerosis necessitates future research. Antihelminthic
      treatment of NC results in disappearance of viable cysts in about one-third of
      patients with parenchymal disease, but a reduction in seizure recurrence has not
      been demonstrated in randomized controlled trials. Prevention is critical to
      reduce the burden of seizure and epilepsy related to NC. 

PMID- 24863517
TI  - Acute ischemic stroke resembling Saturday night palsy.

PMID- 24863518
TI  - Lhermitte-Duclos disease.

PMID- 24863519
TI  - Traumatic brain injury with carotid canal penetrating wound.

PMID- 24863520
TI  - Imaging features that allow for the recognition of Menkes disease.

PMID- 24863521
TI  - Month of birth is not a definite risk factor for multiple sclerosis.

PMID- 24863522
TI  - Nosocomial meningitis caused by Klebsiella pneumoniae producing carbapenemase,
      with initial cerebrospinal fluid minimal inflammatory response.

PMID- 24863524
TI  - Subjective short sleep duration: what does it mean?

PMID- 24863523
TI  - Temporal variation in soluble human leukocyte antigen-G (sHLA-G) and pregnancy
      associated plasma protein A (PAPP-A) in pregnancies complicated by gestational
      diabetes mellitus and in controls.
AB  - PROBLEM: To target gestational diabetes mellitus (GDM) by means of temporal
      variation in pregnancy-associated plasma protein A (PAPP-A) and soluble human
      leukocyte antigen-G (sHLA-G). METHOD OF STUDY: Retrospective analysis of PAPP-A
      and sHLA-G blood levels in historical samples of 112 GDM and 112 controls, drawn
      at first trimester, and prospective study in 18 GDM and 105 controls collected in
      triplicate along the pregnancy. Six hundred and sixty-five samples were analyzed.
      RESULTS: Gestational diabetes mellitus had significantly lower first-trimester
      PAPP-A concentrations than controls (2343+/-1519 versus 2996+/-1955 mU/mL, in
      retrospective brunch and 2490.57+/-1828.52 versus 3240.84+/-1930.69 mU/L in
      prospective one, P<0.001). First-trimester sHLA-G level was significantly lower
      in GDM than in controls (52.88+/-59.69 versus 66.81+/-50.14 ng/mL, P<0.001) and
      increased during gestation in diabetic women showing an opposite trend with
      respect to the controls. CONCLUSION: PAPP-A and sHLA-G are independent markers of
      GDM. Quantitative variations during pregnancy help to early unravel the onset of
      GDM.

PMID- 24863525
TI  - Recommended standards for dental therapy education programs in the United States:
      a summary of critical issues.
AB  - Dental therapy is an accepted component of the dental profession in the Alaska
      Native Tribal Health Consortium and in the state of Minnesota. There are also
      several states working to enact legislation to permit the practice of dental
      therapy. However, in the absence of nationally recognized educational standards,
      concerns have been raised relating to the lack of uniformity in dental therapy
      education. In 2010, a panel of academicians met and prepared a report on the
      principles, competencies, and curriculum for educating dental therapists. Still,
      there remained questions in regard to what the minimal educational standards
      should be for institutions that wish to sponsor dental therapy programs. A second
      panel was convened to address education standards. This paper describes the
      Panel's deliberations on three critical issues in developing the report: the
      length of the program and degree to be awarded; credentials of the program
      director; and the nature of supervision. 

PMID- 24863527
TI  - Haemophilus influenzae stores and distributes hemin by using protein E.
AB  - The human pathogen Haemophilus influenzae causes mainly respiratory tract
      infections such as acute otitis media in children and exacerbations in patients
      with chronic obstructive pulmonary disease. We recently revealed the crystal
      structure of H. influenzeae protein E (PE), a multifunctional adhesin that is
      involved in direct interactions with lung epithelial cells and host proteins.
      Based upon the PE structure we here suggest a hypothetical binding pocket that is
      compatible in size with a hemin molecule. An H. influenzae mutant devoid of PE
      bound significantly less hemin in comparison to the PE-expressing wild type
      counterpart. In addition, E. coli expressing PE at the surface resulted in a
      hemin-binding phenotype. An interaction between hemin and recombinant soluble PE
      was also demonstrated by native-PAGE and UV-visible spectrophotometry. Surface
      plasmon resonance revealed an affinity (Kd) of 1.6 * 10(-6)M for the hemin-PE
      interaction. Importantly, hemin that was bound to PE at the H. influenzae
      surface, was donated to co-cultured luciferase-expressing H. influenzae that were
      starved of hemin. When hemin is bound to PE it thus may serve as a storage pool
      for H. influenzae. To our knowledge this is the first report showing that H.
      influenzae can share hemin via a surface-located outer membrane protein.

PMID- 24863526
TI  - A selective thyroid hormone beta receptor agonist enhances human and rodent
      oligodendrocyte differentiation.
AB  - Nerve conduction within the mammalian central nervous system is made efficient by
      oligodendrocyte-derived myelin. Historically, thyroid hormones have a well
      described role in regulating oligodendrocyte differentiation and myelination
      during development; however, it remains unclear which thyroid hormone receptors
      are required to drive these effects. This is a question with clinical relevance
      since nonspecific thyroid receptor stimulation can produce deleterious side
      effects. Here we report that GC-1, a thyromimetic with selective thyroid receptor
      beta action and a potentially limited side-effect profile, promotes in vitro
      oligodendrogenesis from both rodent and human oligodendrocyte progenitor cells.
      In addition, we used in vivo genetic fate tracing of oligodendrocyte progenitor
      cells via PDGFalphaR-CreER;Rosa26-eYFP double-transgenic mice to examine the
      effect of GC-1 on cellular fate and find that treatment with GC-1 during
      developmental myelination promotes oligodendrogenesis within the corpus callosum,
      occipital cortex and optic nerve. GC-1 was also observed to enhance the
      expression of the myelin proteins MBP, CNP and MAG within the same regions. These
      results indicate that a beta receptor selective thyromimetic can enhance
      oligodendrocyte differentiation in vitro and during developmental myelination in
      vivo and warrants further study as a therapeutic agent for demyelinating models.

PMID- 24863529
TI  - Computational screening of oxetane monomers for novel hydroxy terminated
      polyethers.
AB  - Energetic hydroxy terminated polyether prepolymers find paramount importance in
      search of energetic binders for propellant applications. In the present study,
      density functional theory (DFT) has been employed to screen the various novel
      energetic oxetane derivatives, which usually construct the backbone for these
      energetic polymers. Molecular structures were investigated at the B3LYP/6-31G*
      level, and isodesmic reactions were designed for calculating the gas phase heats
      of formation. The condensed phase heats of formation for designed compounds were
      calculated by the Politzer approach using heats of sublimation. Among the
      designed oxetane derivatives, T4 and T5 possess condensed phase heat of formation
      above 210 kJ mol(-1). The crystal packing density of the designed oxetane
      derivatives varied from 1.2 to 1.6 g/cm(3). The detonation velocities and
      pressures were evaluated using the Kamlet-Jacobs equations, utilizing the
      predicted densities and HOFCond. It was found that most of the designed oxetane
      derivatives have detonation performance comparable to the monomers of benchmark
      energetic polymers viz., NIMMO, AMMO, and BAMO. The strain energy (SE) for the
      oxetane derivatives were calculated using homodesmotic reactions, while
      intramolecular group interactions were predicted through the disproportionation
      energies. The concept of chemical hardness is used to analyze the susceptibility
      of designed compounds to reactivity and chemical transformations. The heats of
      formation, density, and predicted performance imply that the designed molecules
      are expected to be candidates for polymer synthesis and potential molecules for
      energetic binders.

PMID- 24863528
TI  - Mycobacterium avium subsp. paratuberculosis is not discerned in diabetes mellitus
      patients in Hyderabad, India.
AB  - Mycobacterium avium ssp. paratuberculosis (MAP) is an obligate intracellular
      pathogen. It causes chronic intestinal inflammation in ruminants known as Johne's
      disease and is associated with human Crohn's disease. Furthermore, association of
      MAP with other autoimmune diseases, such as type-1 diabetes, has been established
      in patients from Sardinia (Italy) which is a MAP endemic and genetically isolated
      region. Due to largest livestock population and consequently high MAP prevalence
      amidst a very high diabetes incidence in India, we sought to test this
      association on a limited number of patient samples from Hyderabad. Our results of
      ELISA with MAP lysate and MAP-specific protein MAP3738c as well as PCR/real-time
      PCR of MAP-specific sequences IS900 and/or f57 indicated that, in contrast to
      Sardinian diabetic patients, MAP infection in blood is not discerned in diabetic
      patients in Hyderabad. The association of a mycobacterial trigger with diabetes
      therefore could well be a population-specific phenomenon, highly dependent on
      genetic repertoire and the environment of susceptible populations. However, a
      larger study is needed in order to confirm this.

PMID- 24863530
TI  - On the origin of internal rotation in ammonia borane.
AB  - The internal rotation in ammonia borane (AB) was studied on the basis of natural
      orbitals for chemical valence (NOCV) and eigenvectors for Pauli repulsion (NOPR).
      We found that the total hyperconjugation stabilization (ca. 5 kcal mol(-1)),
      based on the charge transfer from the occupied sigma (B-H) orbitals into the
      empty sigma*(N-H), slightly favors the staggered conformation over the eclipsed
      one; however, the barrier to internal rotation in ammonia borane can be
      understood predominantly in a 'classical' way, as originating from the steric
      (Pauli) repulsion contributions (of the kinetic origin) that act solely between N
      H and B-H bonds. Repulsion between the lone pair of ammonia and the adjacent B-H
      bonds was found to be dominant in absolute terms; however, it does not determine
      the rotational barrier. Similar conclusions on the role of CH<->HC repulsion
      appeared to be valid for isoelectronic ethane. 

PMID- 24863532
TI  - Performance of four different force fields for simulations of dipeptide
      conformations: GlyGly, GlyGly-, GlyGly . Cl-, GlyGly . Na+ and GlyGly . (H2O)2.
AB  - Monte-Carlo conformational searches with four kinds of force fields (AMBER94,
      MM3*, MMFFs, and OPLS-2005) were performed on glycylglycine (GlyGly),
      deprotonated glycylglycine (GlyGly(-)), glycylglycine chloride anion complex
      (GlyGly . Cl(-)), glycylglycine sodium cation complex (GlyGly . Na(+)) and
      glycylglycine dihydrate [GlyGly . (H2O)2]. Combined with Hartree-Fock (HF) and
      second-order Moller-Plesset (MP2) optimizations, conformations within an energy
      of 20 kJ mol(-1) were predicted. After MP2 calculations, the geometries and
      relative energies of the predicted structures were the same regardless of the
      force field used. Therefore, the performance of different force fields reflects
      mainly the conformational search process. For GlyGly, there was practically no
      difference among the four force fields. Due to the complex hydrogen bonding
      network when involving water, the total number of resulting conformers for GlyGly
      . (H2O)2 increased drastically. Moreover, the MMFFs force field fared best in
      finding the global minimum compared to the remaining three force fields. In
      describing hydrogen bonded and inter-molecular complexes, we recommend
      application of the MMFFs and AMBER94 force fields. Furthermore, the MMFFs and
      OPLS-2005 force fields have a good description of electrostatic interactions.
      This work will contribute to helping the reader make an optimal choice of force
      field, taking into account the latter's strengths and limitations. 

PMID- 24863531
TI  - DFT and MD study of the divalent-cation-mediated interaction of ochratoxin A with
      DNA nucleosides.
AB  - Aptamers are ligand-binding nucleic acids with affinities and selectivities that
      make them useful for the detection of a variety of compounds, including
      ochratoxin A. Theoretical methods can be applied to study the recognition
      interaction between aptamers and the ochratoxin A molecule. In this work,
      molecular dynamics simulations and quantum chemical calculations performed at the
      DFT level of theory were used to study the structures and energies of aptamers
      and aptamer-ochratoxin A complexes. The optimal structures as well as the
      interaction energies of these structures were elucidated. Divalent cations in the
      water solvent were shown to be an important influence on the structures and
      stabilities of the complexes. 

PMID- 24863533
TI  - REMD and umbrella sampling simulations to probe the energy barrier of the folding
      pathways of engrailed homeodomain.
AB  - Proteins fold by diverse pathways which depend on the energy barriers involved in
      reaching different intermediates. There has been a lot of development in the
      theoretical aspects of protein folding, from force-field to simulation
      techniques. One such simulation approach is replica exchange molecular dynamics
      simulation (REMD), which provides an efficient conformational sampling method to
      understand the events involved in protein folding. In this study, an attempt is
      made to explore the folding funnel of engrailed homeodomain protein (EnHD) using
      REMD simulations. EnHD is a 54 residue long helix bundle protein which has a
      folding time of about 15 MUs. The protein was represented using the Amber United
      atom model in order to reduce the system size which helped to speed up the
      simulation. Individual replicas were simulated for 1.4-2 MUs making cumulative
      time of more than 100 MUs of REMD simulations. Free energy analysis was carried
      out to understand the folding behavior of EnHD protein. Effects of temperature
      range and exchange frequency in REMD simulations have been explored. In addition
      to this, multiple umbrella sampling (US) simulations of a total of 320 ns were
      also carried out, followed by weighted histogram analysis method (WHAM) to
      investigate the energy barriers involved during the folding of various
      intermediates. US studies were also carried on mutational variants of EnHD
      protein to see effect of the mutations on the folding pathway of the protein. The
      use of US technique may be helpful for predicting fast folding mutants or protein
      engineering. The combination of REMD with US may help in understanding the
      energetics between multiple pathways of fast folding proteins and their mutant
      counterparts. 

PMID- 24863534
TI  - Deamination features of 5-hydroxymethylcytosine, a radical and enzymatic DNA
      oxidation product.
AB  - The 5-methylcytosine derivative 5-hydroxymethylcytosine (5hmCyt), which is
      generated via enzymatic oxidation, is sometimes referred to as the sixth
      nucleobase due to its widespread presence in the DNA of brain and embryonic stem
      cells. In this study, we used density functional based methods and reactivity
      indices from conceptual DFT to explore the mechanism and key features of the
      hydrolytic deamination of 5hmCyt. The data obtained are used to compare and
      contrast this deamination reaction with those of other cytosine derivatives. The
      deamination process for 5hmCyt is similar to the corresponding processes for
      other unsaturated derivatives in that the amino form is the reactive one and
      water addition is the rate-limiting step. However, several differences due to the
      rotameric asymmetry of the current system are also noted. 

PMID- 24863537
TI  - Advantages and challenges of small animal magnetic resonance imaging as a
      translational tool.
AB  - The utilization of magnetic resonance imaging (MRI) methods in rodent models of
      psychiatric disorders provides considerable benefits for the identification of
      disease-associated brain circuits and metabolic changes. In this review, we
      discuss advantages and challenges of animal MRI and provide an overview of the
      major structural (voxel-based morphometry and diffusion tensor imaging) and
      functional approaches [resting-state functional MRI (rs-fMRI), MR spectroscopy
      (MRS), regional cerebral blood volume measurement and arterial spin labelling]
      that are applied in animal MRI research. The review mainly focuses on rs-fMRI and
      MRS. Finally, we take a look at some recent developments and refinements in the
      field.

PMID- 24863536
TI  - Drug-drug interactions in HIV positive cancer patients.
AB  - Clinically relevant drug-drug interactions (DDIs) refer to the pharmacological or
      clinical response to the administration or co-exposure of a drug with another
      drug that modifies the patient's response. Treatment regimens, which include
      agents that are involved in the cytochrome P450 (CYP450) enzyme system and
      transporter systems, such as P-glycoprotein may be associated with higher risk of
      clinically significant drug interactions. In addition, potential DDIs increase
      with the increasing number of concomitant drugs. HIV positive cancer patients who
      receive concomitant chemotherapy and combination antiretroviral therapy (cART)
      may achieve better response rates and higher rates of survival than those who
      receive chemotherapy alone, but they may be at increased risk of drug
      interactions. DDIs in HIV positive cancer patients receiving concomitant
      chemotherapy and cART may increase or decrease antineoplastic drug
      concentrations, potentially resulting in life threatening interactions, increased
      toxicity or loss of efficacy. Avoiding and managing potential interactions
      between cART and antineoplastic agents is an increasingly important challenge.
      Based on the current literature, more safety and pharmacokinetic studies are
      needed with the aim to document a clear survival benefit for patients undergoing
      chemotherapy and concomitant or sequential administration of cART. 

PMID- 24863535
TI  - Clinical impact of c-MET expression and genetic mutational status in colorectal
      cancer patients after liver resection.
AB  - c-MET is implicated in the pathogenesis and growth of a wide variety of human
      malignancies, including colorectal cancer (CRC). The aim of the present study was
      to clarify the association between c-MET expression and tumor recurrence in CRC
      patients after curative liver resection, and to evaluate concordance in c-MET
      expression and various mutations of KRAS, BRAF and PIK3CA between primary CRC and
      paired liver metastases. A cohort of patients was tested for c-MET
      immunoreactivity (i.e. immunohistochemistry [IHC]) and KRAS, BRAF and PIK3CA
      mutations. Analyses were performed both on primary tumors and paired liver
      metastases, and the association between IHC and mutations results were assessed.
      A total of 108 patients were eligible. A total of 53% of patients underwent
      simultaneous resection of primary tumors and metastases, and the others underwent
      metachronous resection. Levels of concordance between primary tumors and
      metastases were 65.7%, 87.7%, 100% and 95.2% for c-MET, KRAS, BRAF and PIK3CA,
      respectively. High levels of c-MET expression (c-MET-high) in the primary tumors
      were observed in 52% of patients. Relapse-free survival was significantly shorter
      for patients with c-MET-high primary tumors (9.7 months) than for those with c
      MET-low primary tumors (21.1 months) (P = 0.013). These results suggest that a
      high level of genetic concordance in KRAS, BRAF and PIK3CA between primary tumors
      and liver metastases, and c-MET-high in the primary tumors were associated with
      shorter relapse-free survival after hepatic metastasectomy.

PMID- 24863539
TI  - Sequential hand hygiene promotion contributes to a reduced nosocomial bloodstream
      infection rate among very low-birth weight infants: an interrupted time series
      over a 10-year period.
AB  - BACKGROUND: Sustained high compliance with hand hygiene (HH) is needed to reduce
      nosocomial bloodstream infections (NBSIs). However, over time, a wash out effect
      often occurs. We studied the long-term effect of sequential HH-promoting
      interventions. METHODS: An observational study with an interrupted time series
      analysis of the occurrence of NBSI was performed in very low-birth weight (VLBW)
      infants. Interventions consisted of an education program, gain-framed screen
      saver messages, and an infection prevention week with an introduction on
      consistent glove use. RESULTS: A total of 1,964 VLBW infants admitted between
      January 1, 2002, and December 31, 2011, were studied. The proportion of infants
      with >=1 NBSI decreased from 47.6%-21.2% (P < .01); the number of NBSIs per 1,000
      patient days decreased from 16.8-8.9 (P < .01). Preintervention, the number of
      NBSIs per 1,000 patient days significantly increased by 0.74 per quartile (95%
      confidence interval [CI], 0.27-1.22). The first intervention was followed by a
      significantly declining trend in NBSIs of -1.27 per quartile (95% CI, -2.04 to 
      0.49). The next interventions were followed by a neutral trend change. The
      relative contributions of coagulase-negative staphylococci and Staphylococcus
      aureus as causative pathogens decreased significantly over time. CONCLUSIONS:
      Sequential HH promotion seems to contribute to a sustained low NBSI rate.

PMID- 24863538
TI  - Changes in circulating cytokines and markers of muscle damage in elite cyclists
      during a multi-stage competition.
AB  - The purpose of this study was to determine the changes in the basal and post
      exercise plasma markers of muscular damage, lipid peroxidation and cytokines in
      eight male well-trained semiprofessional cyclists, in response to a three
      consecutive-day cycling competition. Serum markers of oxidative and muscular
      damage - creatine kinase activity, lactate dehydrogenase activity, myoglobin and
      malondialdehyde (MDA), creatinine and nitrite levels - followed a sawtooth-type
      representation throughout the competition. MDA showed an accumulative pattern,
      evidenced in the post-race values of the third stage which were significantly
      higher with respect to the values of the first stage. Cortisol levels were
      significantly influenced by an interaction between the exercise and the stage
      factors, with higher values on the 4th day. Plasma cytokine levels were only
      determined before the first stage and post-race, after the third stage. The
      exercise increased TNFalpha, IL6, IL2 and IFNgamma levels, whereas IL1beta was
      unchanged. In conclusion, cyclist stages induced oxidative and cellular muscle
      damage which is partially recovered to basal values by the next morning.
      Repetitive stages during the cycling competition accumulated plasma muscular
      damage and lipid peroxidation markers and pro-inflammatory cytokines, probably as
      a result of local inflammatory responses. 

PMID- 24863541
TI  - Coordination-driven folding and assembly of a short peptide into a protein-like
      two-nanometer-sized channel.
AB  - Short peptide helices have attracted attention as suitable building blocks for
      soft functional materials, but they are rarely seen in crystalline materials. A
      new artificial nanoassembly of short peptide helices in the crystalline state is
      presented in which peptide helices are arranged three-dimensionally by metal
      coordination. The folding and assembly processes of a short peptide ligand
      containing the Gly-Pro-Pro sequence were induced by silver(I) coordination in
      aqueous alcohol, and gave rise to a single crystal composed of polyproline II
      helices. Crystallographic studies revealed that this material possesses two types
      of unique helical nanochannel; the larger channel measures more than 2 nm in
      diameter. Guest uptake properties were investigated by soaking the crystals in
      polar solutions of guest molecules; anions, organic chiral molecules, and bio
      oligomers are effectively encapsulated by this peptide-folded porous crystal,
      with moderate to high chiral recognition for chiral molecules. 

PMID- 24863540
TI  - Impact of a mandated provincial hand hygiene program: messages from the field.
AB  - BACKGROUND: The British Columbia Provincial Hand Hygiene Working Group was formed
      in September 2010 and tasked with the development and implementation of a
      provincial hand hygiene (HH) program for health care. METHODS: As part of an
      evaluation of the provincial HH program, qualitative key informant interviews of
      program developers, senior administrators, and field workers were performed from
      December 2011 to March 2012 (phase 1) and again in April to June 2013 (phase 2).
      RESULTS: The following 5 broad themes were identified: (1) the provincial HH
      program became a platform for cooperation; (2) standardization (of HH audits and
      program components) strengthened and provided credibility to the provincial HH
      program; (3) quality results and good communication enabled a learning process
      that resulted in positive change management; (4) with ownership came pride and
      program success; and (5) management support and infrastructure is needed to
      sustain a positive culture change. CONCLUSION: Positive behavior change for HH
      can be achieved on a provincial scale through a program that is standardized, has
      mandated components, is well communicated, owned by the frontline workers, and
      receives sustained support from senior management.

PMID- 24863542
TI  - Molecular characterization, genetic diversity and antibacterial susceptibility of
      Escherichia coli encoding Shiga toxin 2f in domestic pigeons.
AB  - This study aimed to evaluate prevalence, characteristics, genotypic diversity and
      antibacterial susceptibility of Escherichia coli encoding Shiga toxin 2f in
      domestic pigeons in different provinces of Iran. A total of 117 faecal samples
      were collected from pigeons and were subjected to molecular detection of stx2f.
      In total, 20, 25.8, 21.4 and 9% of pigeons from Tehran, Ferdows, Garmsar and
      Babol cities carried stx2f+ isolates, respectively. Of the 460 E. coli isolates
      examined, 43 were stx2f+ and most also carried eae (95.3%) and astA (97.7%)
      genes. Some of the stx2f+ isolates harboured cnf (9.3%), but all were negative
      for stx1, stx2 (other subtypes) and ehly. Most Strains (90%) were assigned to B1
      phylogroup and possessed Intimin-beta. Fingerprinting of the stx2f+ isolates
      using either enterobacterial repetitive intergenic consensus sequences (ERIC) or
      random amplified polymorphic DNA (RAPD)-polymerase chain reaction revealed seven
      distinct profiles by each method, with one prevailing (65.1 and 46.5%,
      respectively). By the combination of methods, 10 profiles were recognized. Ten
      isolates from different profiles were shown to belong to O20, O78 and O115
      serogroups, and eight were 100% identical in the stx2f gene sequence. The strains
      were consistently resistant to amoxicillin and lincospectin and commonly
      resistant to tetracycline (88.4%) and doxycycline (74.4%). Overall, the results
      indicate a limited degree of genetic diversity in stx2f-harbouring E. coli from
      pigeons. Significance and impact of the study: Carriage of stx2f gene tends to be
      underreported in pigeon Escherichia coli isolates because most routine genetic
      and phenotypic tests cannot efficiently target this gene or detect the toxin.
      Nevertheless, pigeons frequently carry E. coli strains that are stx2f-positive,
      and this situation is not limited to any distinct geographical area. The current
      results suggest that genetic background of stx2f-encoding E. coli is distinct
      from most Shiga toxin-producing E. coli strains. However, the factors that
      contribute to host preferences and pathogenicity remain unclear. These findings
      have public health significance that should be addressed in future research.

PMID- 24863543
TI  - Cardiovascular implantable electronic devices in hemodialysis patients:
      prevalence and implications for arteriovenous hemodialysis access interventions.
AB  - Cardiovascular implantable electronic devices (CIEDs) are frequently utilized in
      hemodialysis patients. CIED leads are typically implanted via the subclavian vein
      resulting in stenosis and venous hypertension. We studied 1235 chronic
      hemodialysis patients under the care of our nephrology practice. For each, we
      determined the presence of a CIED, indication for implantable cardioverter
      defibrillator (ICD), and type of hemodialysis access. Records were reviewed to
      identify all interventions performed on the access circuit and the central veins
      specifically. A CIED was present in 129 patients (10.5%), including ICDs in 75
      (6.1%) and pacemakers in 54 (4.4%). The access circuit intervention rate was
      1.48/access year (AY) and was similar when a CIED was ipsilateral (1.53/AY) or
      contralateral (1.44/AY) to arteriovenous access (p = 0.477). The rate of central
      venous interventions was greater in the ipsilateral (0.59/AY) versus
      contralateral group (0.28/AY), (p < 0.001). Fifty-four of 59 patients with
      ipsilateral access and CIED required <2 interventions per AY, but six failed
      angioplasty and required access ligation. None had superior vena cava stenosis
      requiring intervention. We conclude that there is a high prevalence of CIEDs in
      our HD patients. Ipsilateral CIED and arteriovenous access results in higher
      central venous intervention rates compared with contralateral cases; overall
      access circuit intervention rates are similar.

PMID- 24863544
TI  - Apical extrusion of debris using ProTaper Universal and ProTaper Next rotary
      systems.
AB  - AIM: To assess and compare the amount of extruded debris after canal preparation
      using ProTaper Universal and ProTaper Next files. METHODOLOGY: Forty extracted
      mandibular premolars with single canals and of similar lengths were instrumented
      using the ProTaper Universal F3 or the ProTaper Next X3. The extruded debris
      during instrumentation was collected into pre-weighed Eppendorf tubes. The tubes
      were stored in an incubator for 5 days. The tubes were weighed to obtain the
      final dry weight of the extruded debris. The amount of apically extruded debris
      was calculated by subtracting the initial weight of the tube from the final
      weight. The distribution of the data was examined using the Shapiro-Wilks test.
      Continuous variables were compared with an independent-samples t-test for two
      groups. RESULTS: All specimens were associated with apical debris extrusion. The
      ProTaper Universal group produced a significantly greater amount of debris
      extrusion (P < 0.001). The lowest and highest amounts of debris for PTU and PTN
      groups were recorded as 0.00117-0.00165 g and 0.00017-0.00067 g, respectively.
      CONCLUSION: ProTaper Next files was associated with significantly less extruded
      apical debris when compared to ProTaper Universal files.

PMID- 24863545
TI  - Impact of unilateral vocal fold mobility impairment on laryngopulmonary
      physiology.
AB  - OBJECTIVE: To examine the impact of unilateral vocal fold mobility impairment
      (UVFMI) on airway physiology. STUDY DESIGN: Cross-sectional observational study.
      PARTICIPANTS: There were 21 patients with UVFMI and 53 controls. MAIN OUTCOME
      MEASURES: All patients and patient controls underwent a maximum-effort flow
      volume loop examination. Forced expiratory flow in one second (FEV1 ), forced
      expiratory volume (FVC), peak inspiratory flow rate and peak expiratory flow rate
      (PIFR and PEFR, respectively) and area under the inspiratory and expiratory flow
      volume loops (AUCI nspiratory and AUCE xpiratory, respectively) were measured.
      The ratio of PEFR to PIFR and AUCE xpiratory to AUCI nspiratory was derived.
      RESULTS: There were 48 males and 26 females. Mean age at measurement was 39 +/-
      11 years. Patients and controls were matched for age, sex, height and weight.
      None of the expiratory variables were significantly different between the groups.
      PIFR was significantly lower in UVFMI patients compared with controls (3.4 +/-
      1.2 versus 5.3 +/- 1.8; P < 0.0001), as was AUCI nspiratory (11.5 +/- 6.3 versus
      17.5 +/- 8.5; P = 0.0002). PEFR/PIFR provided the best differentiation between
      patients with UVFMI and controls with an area under the Receiver Operating
      Characteristic (ROC) curve of 0.96 and at a threshold of 1.9, and PEFR/PIFR had
      sensitivity and specificity of 95.2% and 90.6%, respectively. CONCLUSIONS: Flow
      volume loops are a non-invasive method of studying vocal abduction and could
      compliment voice assessment and laryngoscopy in UVFMI. With further research,
      they could provide an outcome measure for laryngeal rehabilitative procedures,
      and a shared physiological language for screening and surgical quality assurance.

PMID- 24863546
TI  - Lead modulation of macrophages causes multiorgan detrimental health effects.
AB  - The environmental toxicant lead (Pb) has detrimental effects on a number of organ
      systems, including the immune system. Pb exposure decreases host immune defenses
      against numerous microorganisms and cancer. Although Pb effects on humoral and
      cell-mediated immunity as well as on erythrocyte, neural, and renal
      pathophysiology have been well documented, there are few reports regarding Pb's
      impact on innate immunity, which can affect multiorgan processes. This review
      focuses on Pb modulation of a key innate immune cell, the macrophage. The impact
      of Pb on macrophages in different organs, on immature versus mature macrophages,
      and on low versus high Pb concentrations is discussed. Pb decreases phagocytosis
      and chemotaxis of macrophages and affects nitric oxide production and eicosanoid
      metabolism in mature macrophages. Pretreatment of macrophages with Pb increases
      TNF-alpha secretion after in vitro stimulation with lipopolysaccharide; however,
      Pb exposure decreases in vivo intracellular pathogen killing. More recent
      evidence from mouse studies indicates that even low, environmentally relevant,
      blood concentrations of Pb result in increased phagocytosis of erythrocytes and
      decreased expression of interferon-gamma-inducible GTPases, p65-GBP, and p47-IRG,
      which are necessary for intracellular pathogen killing. Taking into account the
      effects of Pb on macrophages, the review describes posited mechanisms to account
      for Pb-altered health effects; Pb effects on heme levels may play a key role as
      well as Pb's preferential induction of helper type-2 T (Th2) cells and M2
      macrophages, which is related to oxidative stress. The discussion links old
      findings with new, thereby adding new insight into the effects of Pb on
      macrophages and the resultant compromised immunity and health. 

PMID- 24863547
TI  - Detection of genetically isolated entities within the Mediterranean species of
      Bemisia tabaci: new insights into the systematics of this worldwide pest.
AB  - BACKGROUND: The taxonomy of the species complex Bemisia tabaci, a serious
      agricultural pest worldwide, is not well resolved yet, even though species
      delimitation is critical for designing effective control strategies. Based on a
      threshold of 3.5% mitochondrial (mtCOI) sequence divergence, recent studies have
      identified 28 putative species. Among them, mitochondrial variability associated
      with particular symbiotic compositions (=cytotypes) can be observed, as in MED,
      which raises the question of whether it is a single or a complex of biological
      species. RESULTS: Using microsatellites, an investigation was made of the genetic
      relatedness of Q1 and ASL cytotypes that belong to MED. Samples of the two
      cytotypes were collected in West Africa where they live in sympatry on the same
      hosts. Genotyping revealed a high level of differentiation, without evidence of
      gene flow. Moreover, they differed highly in frequencies of resistance alleles to
      insecticides, which were much higher in Q1 than in ASL. CONCLUSION: Q1 and ASL
      are sufficiently reproductively isolated for the introgression of neutral alleles
      to be prevented, suggesting that they are actually different species. This
      indicates that nuclear genetic differentiation must be investigated within groups
      with less than 3.5% mtCOI divergence in order to elucidate the taxonomy of B.
      tabaci at a finer level. Overall, these data provide important information for
      pest management.

PMID- 24863548
TI  - Resting frontal EEG asymmetry in children: meta-analyses of the effects of
      psychosocial risk factors and associations with internalizing and externalizing
      behavior.
AB  - Asymmetry of frontal cortical electroencephalogram (EEG) activity in children is
      influenced by the social environment and considered a marker of vulnerability to
      emotional and behavioral problems. To determine the reliability of these
      associations, we used meta-analysis to test whether variation in resting frontal
      EEG asymmetry is consistently associated with (a) having experienced psychosocial
      risk (e.g., parental depression or maltreatment) and (b) internalizing and
      externalizing behavior outcomes in children ranging from newborns to adolescents.
      Three meta-analyses including 38 studies (N = 2,523) and 50 pertinent effect
      sizes were carried out. The studies included in the analyses reported
      associations between frontal EEG asymmetry and psychosocial risk (k = 20;
      predominantly studies with maternal depression as the risk factor) as well as
      internalizing (k = 20) and externalizing (k = 10) behavior outcomes. Psychosocial
      risk was significantly associated with greater relative right frontal asymmetry,
      with an effect size of d = .36 (p < .01), the effects being stronger in girls. A
      non-significant relation was observed between right frontal asymmetry and
      internalizing symptoms (d = .19, p = .08), whereas no association between left
      frontal asymmetry and externalizing symptoms was observed (d = .04, p = .79).
      Greater relative right frontal asymmetry appears to be a fairly consistent marker
      of the presence of familial stressors in children but the power of frontal
      asymmetry to directly predict emotional and behavioral problems is modest.

PMID- 24863549
TI  - From genotype to phenotype; clinical variability in Lesch-Nyhan disease. The role
      of epigenetics.
AB  - Lesch-Nyhan disease is a rare genetic disease characterized by a deficiency in
      the function of the enzyme hypoxanthine-guanine phosphoribosyltransferase
      (HGPRT). Patients affected by this disease experience hyperuricemia, motor
      disorders, mental retardation and, in the most severe cases, self-mutilation. Its
      clinical manifestations depend on the enzymatic activity of HGPRT, which is
      classically linked to the type of alteration in the HGPRT gene. More than 400
      mutations of this gene have been found. At present, one of the controversial
      aspects of the disease is the relationship between the genotype and phenotype;
      cases have been described lacking a mutation, such as the patient presented in
      this article, as well as families who despite sharing the same genetic defect
      show disorders with differing severity. Epigenetic processes, which modify the
      genetic expression without changing the sequence of the deoxyribonucleic acid
      (DNA), could explain the clinical variability observed in this disease. 

PMID- 24863550
TI  - Unusual endosteally formed bone tissue in a patagonian basal sauropodomorph
      dinosaur.
AB  - Mussaurus patagonicus (Dinosauria: Sauropodomorpha) is a basal sauropodomorph
      from the Late Triassic of southern Argentina that is known from a large number of
      individuals, including juveniles, subadults, and adults. Here, we report on the
      occurrence of an unusual bone tissue in an individual of M. patagonicus. The
      rather atypical bone tissue is located within the femoral medullary cavity and
      also occurs within several erosion cavities of the midinner part of the cortex.
      This tissue is well vascularized and is composed of a matrix that consists of
      abundant and densely packed osteocyte lacunae. Although some features of this
      tissue resembles avian medullary bone, the histological features are distinctive
      and share more features with the pathological, reactive bone produced in extant
      birds in response to a retrovirus-induced disease (avian osteopetrosis). Here, we
      also discuss and provide histological features to effectively differentiate
      endosteally formed medullary bone from pathological avian osteopetrosis.

PMID- 24863552
TI  - A multistate pH-triggered nonlinear optical switch.
AB  - By using hyper-Rayleigh scattering experiments and quantum-chemical calculations,
      we demonstrate that nonlinear optics can be used to probe unequivocally, within a
      non-destructive process, the multiple electronic states that are activated upon
      pH- and light-triggered transformations of the 4'-hydroxyflavylium ion. These
      results open new perspectives in the design of molecular-scale high-density
      optical memory. 

PMID- 24863553
TI  - Measuring trade-offs that matter: assessing the impact of a new electronic cross
      match policy on the turnaround time and the cross-match workload efficiency.
AB  - BACKGROUND: Our traditional cross-match (XM) policy generated a significant
      number of XM units that were never issued. To minimize the unnecessary XM
      workload, we proposed a new policy where orders eligible for the electronic XM
      (EXM) are pended until orders to issue red blood cells (RBCs) are received. To
      address concerns that this new policy might unduly delay blood availability, we
      conducted a study to assess whether the new policy was noninferior to the
      traditional policy with regard to the turnaround time (TAT). STUDY DESIGN AND
      METHODS: We monitored the TAT and XM workload efficiency (XM-to-issue [C : I]
      ratio) for a total of 8 weeks split between the two policies' periods. The
      primary outcome was the proportion of RBC issue requests that was turned around
      in less than 12 minutes. RESULTS: Fifty percent (1133 of 2265) of issue requests
      were turned around in 12 minutes or less under the traditional policy compared to
      43.9% (975 of 2223) under the new policy (absolute difference of 6.1%; 95%
      confidence interval [CI], 3.2%-9.1%; p < 0.001). The adjusted overall median TAT
      was slower by 1 minute (13 min vs. 14 min, p < 0.001) but the adjusted C : I
      ratio was better (1.00 vs. 1.15; p < 0.001) under the new policy. CONCLUSION: Our
      study showed that the impact of the new policy on the TAT was not inferior to the
      traditional policy. Since the median TAT of 14 minutes under the new policy met
      the published benchmarks, the trade-off between delays in the TAT and efficiency
      gains in the XM workload remained acceptable for patient care.

PMID- 24863551
TI  - Age- and sex-specific criterion validity of the health survey for England
      Physical Activity and Sedentary Behavior Assessment Questionnaire as compared
      with accelerometry.
AB  - The criterion validity of the 2008 Physical Activity and Sedentary Behavior
      Assessment Questionnaire (PASBAQ) was examined in a nationally representative
      sample of 2,175 persons aged >=16 years in England using accelerometry. Using
      accelerometer minutes/day greater than or equal to 200 counts as a criterion,
      Spearman's correlation coefficient (rho) for PASBAQ-assessed total activity was
      0.30 (95% confidence interval (CI): 0.25, 0.35) in women and 0.20 (95% CI: 0.15,
      0.26) in men. Correlations between accelerometer counts/minute of wear time and
      questionnaire-assessed relative energy expenditure (metabolic equivalent
      minutes/day) were higher in women (rho = 0.41, 95% CI: 0.36, 0.46) than in men
      (rho = 0.32, 95% CI: 0.26, 0.38). Similar correlations were observed for
      minutes/day spent in vigorous activity (women: rho = 0.39, 95% CI: 0.33, 0.46;
      men: rho = 0.31, 95% CI: 0.26, 0.36) and moderate-to-vigorous activity (women:
      rho = 0.42, 95% CI: 0.36, 0.48; men: rho = 0.38, 95% CI: 0.32, 0.45).
      Correlations for time spent being sedentary (<100 counts/minute) were 0.30 (95%
      CI: 0.24, 0.35) and 0.25 (95% CI: 0.19, 0.30) in women and men, respectively.
      Sedentary behavior correlations showed no sex difference. The validity of
      sedentary behavior and total physical activity was higher in older age groups,
      but validity was higher in younger persons for vigorous-intensity activity. The
      PASBAQ is a useful and valid instrument for ranking individuals according to
      levels of physical activity and sedentary behavior.

PMID- 24863555
TI  - Development, optimization and validation of a highly sensitive UPLC-ESI-MS/MS
      method for simultaneous quantification of amlodipine, benazeprile and
      benazeprilat in human plasma: application to a bioequivalence study.
AB  - A rapid, simple, sensitive and specific LC-MS/MS method has been developed and
      validated for the simultaneous estimation of amlodipine (AML), benazepril (BEN)
      and benazeprilat (BNT) using eplerenone and torsemide as internal standards (IS).
      The Xevo TQD LC-MS/MS was operated under the multiple-reaction monitoring mode
      using electrospray ionization. Sample preparation involves both extraction and
      precipitation techniques. The reconstituted samples were chromatographed on
      Acquity UPLC BEH C18 (50mm*2.1mm, 1.7MUm) column by pumping 0.1% formic acid and
      acetonitrile in a gradient mode at a flow rate of 0.45ml/min. A detailed
      validation of the method was performed as per the FDA guidelines and the standard
      curves were found to be linear in the range of 0.1-5ng/ml for AML; 5-1200ng/ml
      for both BEN and BNT. The intra-day and inter-day precision and accuracy results
      were within the acceptable limits. A run time of 2.5min for each sample made it
      possible to analyze more than 300 human plasma samples per day. The developed
      assay method was successfully applied to a bioequivalence study in human
      volunteers. 

PMID- 24863556
TI  - Selective detection of ferric ions by blue-green photoluminescent nitrogen-doped
      phenol formaldehyde resin polymer.
AB  - The smaller, the more fluorescent: The hydrothermal reaction of phenol with
      hexamethylenetetramine (HMT) leads to two morphologies of phenol formaldehyde
      resin (PFR), namely, bigger nanoparticles with feeble green fluorescence and
      smaller amorphous polymers with strong blue-green fluorescence. It reveals that
      both of them are doped with nitrogen, and the blue-green photoluminescent polymer
      is confirmed to sense ferric ion (Fe(3+) ) with high selectivity. 

PMID- 24863558
TI  - Skin texture aging trend analysis using dermoscopy images.
AB  - BACKGROUND/PURPOSE: To date, the degree of skin damage caused by diverse factors,
      such as aging and persistent sunlight exposure, has been evaluated based on the
      personal experience and knowledge of dermatologists because there is no standard
      method for objective evaluation. If a standard method were available, patients
      could obtain more consistent information about their skin condition, and hence
      perform more effective treatment of the skin damage. In this paper, we
      demonstrate how to establish a standard method using dermoscopy images of
      subjects of various ages. We focus on three body parts, specifically the face,
      neck, and hands, and extract various skin texture features to quantitatively and
      objectively represent the skin condition. METHOD: We construct a model for skin
      damage evaluation based on various skin texture features. To accomplish this
      objective, we consider various features from face, neck, and hand dermoscopy
      images, including texture length, width and depth, cell area, the number of cells
      in a fixed region, radius ratio of inscribed and circumscribed circles of a
      wrinkle cell, and average perimeter of a wrinkle cell. In this study, a wrinkle
      cell represents the smallest skin region enclosed by textures. We then perform a
      linear regression for texture features based on subject age. RESULT: A dermoscopy
      image can be automatically analyzed by extracting skin texture features. We
      demonstrate aging trends by performing linear regression on these features. Based
      on this result, a quantitative and objective evaluation of the skin condition can
      be provided. CONCLUSION: We proposed several new skin texture features and
      developed algorithms to accurately extract them. We analyzed these features and
      demonstrated their age-related change trends by using graphs and charts. We
      believe that our result can be used as a standard method for evaluating degrees
      of skin damage. Moreover, we believe that our proposed method can be applied in
      various areas, such as performance evaluation of certain skin products.

PMID- 24863557
TI  - Biphasic beta-TCP mixed with silicon increases bone formation in critical site
      defects in rabbit calvaria.
AB  - OBJECTIVE: The aim of this study was to assess the bone regeneration of critical
      size defects in rabbit calvarias filled with beta-TCP doped with silicon.
      MATERIALS AND METHODS: Twenty-one New Zealand rabbits were used in this study.
      Two critical size defects were created in the parietal bones. Three experimental
      groups were evaluated: Test A (HA/beta-TCP granules alone), Test B (HA/beta-TCP
      granules plus 3% silicon), Control (empty defect). The animals were sacrificed at
      8 and 12 weeks. Evaluation was performed by MUCT analysis and histomorphometry.
      RESULTS: MUCT evaluation showed higher volume reduction in Test A group compared
      with Test B (P < 0.05). The Test B group showed the highest values for cortical
      closure and bone formation around the particles, followed by Test A and controls
      (P < 0.05). CONCLUSIONS: Within the limitations of this animal study, it can be
      concluded that HA/beta-TCP plus 3% silicon increases bone formation in critical
      size defects in rabbit calvarias, and the incorporation of 3% silicon reduces the
      resorption rate of the HA/beta-TCP granules.

PMID- 24863559
TI  - Energy recovery from solutions with different salinities based on swelling and
      shrinking of hydrogels.
AB  - Several technologies, including pressure-retarded osmosis (PRO), reverse
      electrodialysis (RED), and capacitive mixing (CapMix), are being developed to
      recover energy from salinity gradients. Here, we present a new approach to
      capture salinity gradient energy based on the expansion and contraction
      properties of poly(acrylic acid) hydrogels. These materials swell in fresh water
      and shrink in salt water, and thus the expansion can be used to capture energy
      through mechanical processes. In tests with 0.36 g of hydrogel particles 300 to
      600 MUm in diameter, 124 mJ of energy was recovered in 1 h (salinity ratio of
      100, external load of 210 g, water flow rate of 1 mL/min). Although these energy
      recovery rates were relatively lower than those typically obtained using PRO,
      RED, or CapMix, the costs of hydrogels are much lower than those of membranes
      used in PRO and RED. In addition, fouling might be more easily controlled as the
      particles can be easily removed from the reactor for cleaning. Further
      development of the technology and testing of a wider range of conditions should
      lead to improved energy recoveries and performance. 

PMID- 24863560
TI  - Trimodality therapy and definitive chemoradiotherapy for esophageal cancer: a
      single-center experience and review of the literature.
AB  - In the UK, the standard of care for esophageal cancer has generally combined
      surgery with neoadjuvant chemotherapy, with definitive chemoradiotherapy (dCRT)
      being reserved for certain subgroups. Chemoradiotherapy followed by surgery
      (trimodality therapy) has not been widely adopted. The outcomes of patients
      undergoing dCRT or trimodality therapy at our cancer center between 2004 and 2012
      were restrospectively analyzed. Trimodality therapy was offered to selected
      patients of good performance status (World Health Organisation performance status
      0/1), with squamous cell carcinoma or bulky adenocarcinoma. dCRT was offered to
      patients of good PS but with comorbidities, upper third tumors or at patient's
      request. Patients received four cycles of chemotherapy with a platinum agent
      (mostly cisplatin) and a fluoropyrimidine (mostly 5-fluorouracil) over a total of
      11 weeks. Cycles 3 and 4 were given concurrently with radiotherapy: 50 Gy in 25
      fractions for dCRT and 45 Gy in 25 fractions in the trimodality group. Surgery
      occurred 8-10 weeks following the completion of chemoradiotherapy. The cut-off
      length for maximum gross tumor volume length was 10 cm. One hundred two patients
      were included (47 received dCRT, and 55 received trimodality treatment). The
      majority of tumors were stage III (80.4%), and two-thirds were located in the
      distal esophagus (64.7%). Median follow-up was 44 months. The 2-year overall
      survival (OS) was 57.3% (median OS 39.7 months) for the dCRT group and 77.8%
      (median not reached) for the trimodality group. The 5-year OS rates were 38% and
      58%, respectively. Postoperative mortality rate was low at 1.8%, and the
      pathological complete response rate was 23.6%. In conclusion, trimodality
      treatment for patients with esophageal and junctional gastroesophageal tumors
      offers high rates of 2-year survival, and the potential for long-term cure. dCRT
      is an established alternative for patients that are not fit or suitable for
      surgery.

PMID- 24863561
TI  - Identification and characterization of a multispecific monoclonal antibody G2
      against chicken prion protein.
AB  - We previously generated a monoclonal antibody (mAb), G2, by immunizing mice with
      Residues 174-247 of the chicken prion protein (ChPrP(C) ). In this study, we
      found that G2 possessed an extremely unusual characteristic for a mAb; in
      particular, it could react with at least three proteins other than ChPrP(C) , the
      original antigenic protein. We immunoscreened a complementary DNA library from
      chicken brain DNA and found three proteins (SEPT3, ATP6V1C1, and C6H10orf76) that
      reacts with G2. There were no regions of amino acid sequence similarity between
      ChPrP(C) and SEPT3, ATP6V1C1, or C6H10orf76. We selected ATP6V1C1 as a
      representative of the three proteins and identified the epitope within ATP6V1C1
      that reacts with G2. The amino acid sequence of the G2 epitope within ATP6V1C1
      (Pep8) was not related to the G2 epitope within ChPrP(C) (Pep18mer). However,
      enzyme-linked immunosorbent assay, surface plasmon resonance (SPR), and
      isothermal titration calorimetry (ITC) experiments indicated that these two
      peptides have similar binding affinity for G2. The apparent KD values of Pep18mer
      and Pep8 obtained from SPR experiments were 2.9 * 10(-8) and 1.6 * 10(-8) M,
      respectively. Antibody inhibition test using each peptide indicated that the
      binding sites of the two different peptides overlapped each other. We observed
      that these two peptides substantially differed in several binding
      characteristics. Based on the SPR experiments, the association and dissociation
      rate constants of Pep18mer were higher than those of Pep8. A clear difference was
      also observed in ITC experiments. These differences may be explained by G2
      adopting different binding conformations and undergoing different binding
      pathways. 

PMID- 24863562
TI  - A Meloidogyne incognita effector is imported into the nucleus and exhibits
      transcriptional activation activity in planta.
AB  - Root-knot nematodes are sedentary biotrophic endoparasites that maintain a
      complex interaction with their host plants. Nematode effector proteins are
      synthesized in the oesophageal glands of nematodes and secreted into plant tissue
      through a needle-like stylet. Effectors characterized to date have been shown to
      mediate processes essential for nematode pathogenesis. To gain an insight into
      their site of action and putative function, the subcellular localization of 13
      previously isolated Meloidogyne incognita effectors was determined. Translational
      fusions were created between effectors and EGFP-GUS (enhanced green fluorescent
      protein-beta-glucuronidase) reporter genes, which were transiently expressed in
      tobacco leaf cells. The majority of effectors localized to the cytoplasm, with
      one effector, 7H08, imported into the nuclei of plant cells. Deletion analysis
      revealed that the nuclear localization of 7H08 was mediated by two novel
      independent nuclear localization domains. As a result of the nuclear localization
      of the effector, 7H08 was tested for the ability to activate gene transcription.
      7H08 was found to activate the expression of reporter genes in both yeast and
      plant systems. This is the first report of a plant-parasitic nematode effector
      with transcriptional activation activity. 

PMID- 24863563
TI  - The national burden of cerebrovascular diseases in Spain: a population-based
      study using disability-adjusted life years.
AB  - BACKGROUND AND OBJECTIVE: The aim of the present study was to determine the
      national burden of cerebrovascular diseases in the adult population of Spain.
      PATIENTS AND METHODS: Cross-sectional, descriptive population-based study. We
      calculated the disability-adjusted life years (DALY) metric using country
      specific data from national statistics and epidemiological studies to obtain
      representative outcomes for the Spanish population. DALYs were divided into years
      of life lost due to premature mortality (YLLs) and years of life lived with
      disability (YLDs). DALYs were estimated for the year 2008 by applying demographic
      structure by sex and age-groups, cause-specific mortality, morbidity data and new
      disability weights proposed in the recent Global Burden of Disease study. In the
      base case, neither YLLs nor YLDs were discounted or age-weighted. Uncertainty
      around DALYs was tested using sensitivity analyses. RESULTS: In Spain,
      cerebrovascular diseases generated 418,052 DALYs, comprising 337,000 (80.6%) YLLs
      and 81,052 (19.4%) YLDs. This accounts for 1,113 DALYs per 100,000 population
      (men: 1,197 and women: 1,033) and 3,912 per 100,000 in those over the age of 65
      years (men: 4,427 and women: 2,033). Depending on the standard life table and
      choice of social values used for calculation, total DALYs varied by 15.3% and
      59.9% below the main estimate. CONCLUSIONS: Estimates provided here represent a
      comprehensive analysis of the burden of cerebrovascular diseases at a national
      level. Prevention and control programmes aimed at reducing the disease burden
      merit further priority in Spain.

PMID- 24863564
TI  - Glenohumeral relationships at different angles of abduction.
AB  - PURPOSE: The objective of this study was to clarify the relationships among
      anatomical landmarks of the glenohumeral joint at different angles of abduction.
      METHODS: Fifteen volunteers (ten men, five women; mean age 29 years) were
      enrolled in this study. Images of externally and internally rotated positions at
      45 degrees , 90 degrees , and 135 degrees  of abduction in the plane 30 degrees 
      anterior to the trunk were taken using an open magnetic resonance imaging system.
      Landmarks including the glenoidal long axis with its center, bicipital groove,
      center of the head, and humeral shaft axis were determined. Using a line set on
      the surface of the head in the plane parallel to the humeral axis (including the
      head center and bicipital groove with its parallel and perpendicular lines), the
      glenoid location and rotational relationships were investigated in each position.
      RESULTS: The average angles of axial rotation were 48 degrees  +/- 27 degrees  at
      45o of abduction, 71 degrees  +/- 20 degrees  at 90 degrees  of abduction, and 40
      degrees  +/- 27 degrees  at 135 degrees  of abduction. The trajectories of the
      glenoid center primarily extended over the anterior portion of the humeral head
      at 45 degrees  of abduction and over the posterior portion at 90 degrees  of
      abduction, while those at 135 degrees  of abduction were localized on a small
      upper portion of the head. CONCLUSIONS: The glenohumeral relationships
      demonstrated that arm abduction might influence shoulder function through its
      effects on the portion of the humeral surface in contact with the glenoid during
      rotation and the resultant changes in the glenohumeral relationships.

PMID- 24863566
TI  - An unusual breast lesion: granular cell tumor of the breast with extensive chest
      wall invasion.
AB  - Granular cell tumors (GCT) are generally benign soft tissue tumors. When located
      in the breast, they may be misdiagnosed as more typical tumors, such as invasive
      ductal carcinoma, based on misleading clinical or radiologic features. GCTs are
      frequently found in the setting of a known malignancy. We report the case of a
      patient with a large infra-mammary fold GCT, the management of which required a
      multidisciplinary operative approach due to extensive chest wall invasion.

PMID- 24863565
TI  - Stimulus-specific adaptation in field potentials and neuronal responses to
      frequency-modulated tones in the primary auditory cortex.
AB  - In order to structure the sensory environment our brain needs to detect changes
      in the surrounding that might indicate events of presumed behavioral relevance. A
      characteristic brain response presumably related to the detection of such novel
      stimuli is termed mismatch negativity (MMN) observable in human scalp recordings.
      A candidate mechanism underlying MMN at the neuronal level is stimulus-specific
      adaptation (SSA) which has several characteristics in common. SSA is the specific
      decrease in the response to a frequent stimulus, which does not generalize to an
      interleaved rare stimulus in a sequence of events. SSA was so far mainly
      described for changes in the response to simple pure tone stimuli differing in
      tone frequency. In this study we provide data from the awake rat auditory cortex
      on adaptation in the responses to frequency-modulated tones (FM) with the
      deviating feature being the direction of FM modulation. Adaptation of cortical
      neurons to the direction of FM modulation was stronger for slow modulation than
      for faster modulation. In contrast to pure tone SSA which showed no stimulus
      preference, FM adaptation in neuronal data differed sometimes between upward and
      downward FM. This, however, was not the case in the local field potential data
      recorded simultaneously. Our findings support the role of the auditory cortex as
      the source for change-related activity induced by FM stimuli by showing that
      dynamic stimulus features such as FM modulation can evoke SSA in the rat in a way
      very similar to FM-induced MMN in the human auditory cortex. 

PMID- 24863568
TI  - Phytomedicine. Editorial.

PMID- 24863567
TI  - Detoxification of insecticides, allechemicals and heavy metals by glutathione S
      transferase SlGSTE1 in the gut of Spodoptera litura.
AB  - Insect glutathione S-transferases (GSTs) play important roles in detoxifying
      toxic compounds and eliminating oxidative stress caused by these compounds. In
      this study, detoxification activity of the epsilon GST SlGSTE1 in Spodoptera
      litura was analyzed for several insecticides and heavy metals. SlGSTE1 was
      significantly up-regulated by chlorpyrifos and xanthotoxin in the midgut of S.
      litura. The recombinant SlGSTE1 had Vmax (reaction rate of the enzyme saturated
      with the substrate) and Km (michaelis constant and equals to the substrate
      concentration at half of the maximum reaction rate of the enzyme) values of 27.95
      +/- 0.88 MUmol/min/mg and 0.87 +/- 0.028 mmol/L for glutathione, respectively,
      and Vmax and Km values of 22.96 +/- 0.78 MUmol/min/mg and 0.83 +/- 0.106 mmol/L
      for 1-chloro-2,4-dinitrobenzene, respectively. In vitro enzyme indirect activity
      assay showed that the recombinant SlGSTE1 possessed high binding activities to
      the insecticides chlorpyrifos, deltamethrin, malathion, phoxim and dichloro
      diphenyl-trichloroethane (DDT). SlGSTE1 showed higher binding activity to toxic
      heavy metals cadmium, chromium and lead than copper and zinc that are required
      for insect normal growth. Western blot analysis showed that SlGSTE1 was induced
      in the gut of larvae fed with chlorpyrifos or cadmium. SlGSTE1 also showed high
      peroxidase activity. All the results together indicate that SlGSTE1 may play an
      important role in the gut of S. litura to protect the insect from the toxic
      effects of these compounds and heavy metals. 

PMID- 24863569
TI  - Be Mindful of What You Impose on Your Colleagues: Implications of Social Burden
      for Burdenees' Well-being, Attitudes and Counterproductive Work Behaviour.
AB  - This paper describes two studies of a new relational variable social burden and
      its implications for employees' well-being, job attitudes and counterproductive
      work behaviours. Social burden is defined as behaviours from colleagues that
      elicit the focal employees' social support. Across two separate samples (540
      nurses and 172 university employees), we found that social burden differentiated
      from psychological aggression and incivility, respectively. A separate cross
      sectional sample of 273 nurses from Study 1 revealed that social burden from
      colleagues was positively associated with focal employees' anxiety, irritation,
      depressive mood, physical symptoms, job dissatisfaction and turnover intentions.
      Study 2 used a time-lagged design with a separate sample of 383 university
      employees and 160 of their coworkers. In this study, social burden from
      supervisors and from coworkers were together predictive of employees' subsequent
      emotional strains and job attitudes, as measured 6 months later. With respect to
      sources of social burden, social burden from supervisors more strongly predicted
      job attitudes and counterproductive work behaviours directed at others, and
      social burden from coworkers more strongly predicted emotional strains.

PMID- 24863571
TI  - Cryptic diversity hides host and habitat specialization in a gorgonian-algal
      symbiosis.
AB  - Shallow water anthozoans, the major builders of modern coral reefs, enhance their
      metabolic and calcification rates with algal symbionts. Controversy exists over
      whether these anthozoan-algae associations are flexible over the lifetimes of
      individual hosts, promoting acclimative plasticity, or are closely linked, such
      that hosts and symbionts co-evolve across generations. Given the diversity of
      algal symbionts and the morphological plasticity of many host species, cryptic
      variation within either partner could potentially confound studies of anthozoan
      algal associations. Here, we used ribosomal, organelle and nuclear sequences,
      along with microsatellite variation, to study the relationship between lineages
      of a common Caribbean gorgonian and its algal symbionts. The gorgonian Eunicea
      flexuosa is a broadcast spawner, composed of two recently diverged, genetically
      distinct lineages largely segregated by depth. We sampled colonies of the two
      lineages across depth gradients at three Caribbean locations. We find that each
      host lineage is associated with a unique Symbiodinium B1/184 phylotype. This
      relationship between host and symbiont is maintained when host colonies are
      reciprocally transplanted, although cases of within phylotype switching were also
      observed. Even when the phylotypes of both partners are present at intermediate
      depths, the specificity between host and symbiont lineages remained absolute.
      Unrecognized cryptic diversity may mask host-symbiont specificity and change the
      inference of evolutionary processes in mutualistic associations. Symbiotic
      specificity thus likely contributes to the ecological divergence of the two
      partners, generating species diversity within coral reefs.

PMID- 24863570
TI  - Improving acne keloidalis nuchae with targeted ultraviolet B treatment: a
      prospective, randomized, split-scalp comparison study.
AB  - BACKGROUND: Acne keloidalis nuchae (AKN) is a chronic scarring folliculitis with
      fibrotic papules on the occipital scalp. Its treatment is limited and
      unsatisfactory. OBJECTIVES: To determine whether targeted ultraviolet B (tUVB)
      phototherapy will (i) improve the clinical appearance of AKN and (ii) induce
      extracellular matrix remodelling in affected lesions. METHODS: Eleven patients
      with AKN were enrolled in a prospective, randomized, split-scalp comparison
      study. One randomly selected side of the scalp was treated with tUVB up to three
      times weekly for 8 weeks. After week 8, both sides were treated for eight
      additional weeks. Assessment included lesion counts in two 3 * 3-cm regions of
      interest (ROIs), one on each side of the scalp (ROI-1: tUVB weeks 0-16, ROI-2:
      tUVB weeks 9-16), patient self-assessment and analysis of MMP1, MMP9, TGFB1 and
      COL1A1 mRNA expression by quantitative reverse-transcription polymerase chain
      reaction. RESULTS: Before treatment, the mean lesion count was similar between
      tUVB-treated and untreated sides (14.8 vs. 15.0). After 8 weeks of tUVB, the mean
      lesion count decreased significantly to 9.4 +/- 1.2 (P =  0.03), with no change
      on the untreated side. With continued treatment, the mean lesion count in ROI-1
      decreased further to 7 +/- 1.5 (P = 0.04) after 16 weeks of tUVB. CONCLUSIONS:
      tUVB significantly improved the clinical appearance of AKN, led to patient
      satisfaction and was well tolerated.

PMID- 24863575
TI  - A loonie for your thoughts?

PMID- 24863572
TI  - Antibody responses induced by Leish-Tec(r), an A2-based vaccine for visceral
      leishmaniasis, in a heterogeneous canine population.
AB  - Zoonotic visceral leishmaniasis (VL) is a widespread disease, and dogs are the
      main reservoirs for human parasite transmission. Hence, development of an
      effective vaccine that prevents disease and reduces the transmission of VL is
      required. As euthanasia of seropositive dogs is recommended in Brazil for VL
      epidemiological control, to include anti-VL canine vaccines as a mass control
      measure it is necessary to characterize the humoral responses induced by
      vaccination and if they interfere with the reactivity of vaccinated dogs in
      serological diagnostic tests. Leish-Tec((r)) is an amastigote-specific A2
      recombinant protein vaccine against canine visceral leishmaniasis (CVL) that is
      commercially available in Brazil. Here, we tested the immunogenicity of Leish
      Tec((r)) in a heterogeneous dog population by measuring A2-specific antibody
      responses. Healthy dogs (n=140) of various breeds were allocated to two groups:
      one group received Leish-Tec((r)) (n=70), and the other group received a placebo
      (n=70). Anti-A2 or anti-Leishmania promastigote antigen (LPA) antibody levels
      were measured by ELISA in serum samples collected before and after vaccination.
      An immunochromatographic test (DPP) based on the recombinant K28 antigen was also
      used for serodiagnosis of CVL. Vaccinated animals, except one, remained
      seronegative for anti-LPA total IgG and anti-K28 antibodies. Conversely,
      seropositivity for anti-A2 total IgG antibodies was found in 98% of animals after
      vaccination. This value decreased to 81.13% at 6 months before rising again
      (98%), after the vaccination boost. Anti-A2 IgG2 and IgG1 titers were also
      increased in vaccinated animals relative to control animals. These data indicate
      that Leish-Tec((r)) is immunogenic for dogs of different genetic backgrounds and
      that humoral responses induced by vaccination can be detected by A2-ELISA, but do
      not interfere with the LPA-ELISA and DPP diagnostic tests for CVL. 

PMID- 24863574
TI  - The segment as the minimal planning unit in speech production: evidence based on
      absolute response latencies.
AB  - A minimal amount of information about a word must be phonologically and
      phonetically encoded before a person can begin to utter that word. Most
      researchers assume that the minimum is the complete word or possibly the initial
      syllable. However, there is some evidence that the initial segment is sufficient
      based on longer durations when the initial segment is primed. In two experiments
      in which the initial segment of a monosyllabic word is primed or not primed, we
      present additional evidence based on very short absolute response times
      determined on the basis of acoustic and articulatory onset relative to
      presentation of the complete target. We argue that the previous failures to find
      very short absolute response times when the initial segment is primed are due in
      part to the exclusive use of acoustic onset as a measure of response latency, the
      exclusion of responses with very short acoustic latencies, the manner of
      articulation of the initial segment (i.e., plosive vs. nonplosive), and
      individual differences. Theoretical implications of the segment as the minimal
      planning unit are considered. 

PMID- 24863577
TI  - Better health, better care, better value: National Expert Commission, part 1.
AB  - Since about the midway point of the First Ministers' 10-year plan to strengthen
      healthcare, its impending expiry in 2014 has prompted the leading health
      professions to consider "what comes next," how to influence that decision and
      then, how best to position their messages in the politics of whatever might
      emerge. The Canadian Nurses Association (CNA), which has a century-long history
      of engagement in health policy, was no exception. 

PMID- 24863573
TI  - Mesenchymal stem cells are sensitive to treatment with kinase inhibitors and
      ionizing radiation.
AB  - INTRODUCTION: Mesenchymal stem cells (MSCs) can regenerate damaged tissues and
      may therefore be of importance for normal tissue repair after cancer treatment.
      Small molecule receptor kinase inhibitors (RKIs) have recently been introduced
      into cancer treatment. However, the influence of these drugs-particularly in
      combination with radiotherapy-on the survival of MSCs is largely unknown.
      METHODS: The sensitivity of human primary MSCs from healthy volunteers and
      primary human fibroblast cells to small molecule kinase inhibitors of the
      vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF)
      and transforming growth factor beta (TGFbeta) receptors, as well to inhibitors of
      c-Kit, was examined in combination with ionizing radiation (IR); cell survival
      and proliferation were assessed. Expression patterns of different kinase
      receptors and ligands were investigated using gene arrays. RESULTS: MSCs were
      highly sensitive to the tyrosine kinase inhibitors SU14816 (imatinib) and SU11657
      (sunitinib), but showed only moderate sensitivity to the selective TGFbeta
      receptor 1 inhibitor LY2109761. Primary adult human fibroblasts were comparably
      resistant to all three inhibitors. The addition of IR had an additive or supra
      additive effect in the MSCs, but this was not the case for differentiated
      fibroblasts. Proliferation was markedly reduced in MSCs following kinase
      inhibition, both with and without IR. Gene expression analysis revealed high
      levels of the PDGF alpha and beta receptors, and lower levels of the TGFbeta
      receptor 2 and Abl kinase. IR did not alter the expression of kinase receptors or
      their respective ligands in either MSCs or adult fibroblasts. CONCLUSION: These
      data show that MSCs are highly sensitive to RKIs and combination treatments
      incorporating IR. Expression analyses suggest that high levels of PDGF receptors
      may contribute to this effect.

PMID- 24863578
TI  - Scholarship in nursing: current view.
AB  - Knowledge, as it relates to scholarship, has traditionally been developed through
      research, which for years was viewed as the sole method of knowledge generation.
      An expanded view of scholarship was proposed by Boyer, and includes the
      scholarship of discovery, integration, teaching, and application. This broader
      framework of scholarship is more suited to today's world. The aim of this paper
      is to provide clarification regarding the definition and criteria of scholarship
      and the differences between scholarly activities and scholarship. Nurses are held
      to the same standards of knowledge generation as other disciplines. There should
      be clarity on differentiating scholarly activities from scholarship. 

PMID- 24863579
TI  - Thoughts on practice scholarship.

PMID- 24863580
TI  - Moving knowledge to action: a qualitative study of the Registered Nurses'
      Association of Ontario Advanced Clinical Practice Fellowship program.
AB  - With funding from the Ontario Ministry of Health and Long-Term Care, the
      Registered Nurses' Association of Ontario (RNAO) established the Advanced
      Clinical Practice Fellowship (ACPF) program in 2000 to improve patient care and
      outcomes through advanced nursing knowledge and skills. This paper describes the
      perceptions of ACPF fellows regarding their influence on quality of care and
      patient outcomes, specifically, the types of practice change activities
      initiated, successful implementation and influence on outcomes, barriers
      encountered and strategies used to address them and influence change. METHODS:
      Thirty telephone interviews were conducted with ACPF fellows after completing
      their fellowship. Interviews were analyzed using descriptive content analysis.
      RESULTS: Fifty-one practice change activities were identified. Ratings for
      successful implementation (1 = not successful, 10 = extremely successful) were
      7.2/10; ratings for successful influence on outcomes were 7.4/10. Barriers
      identified were (a) resistant attitudes, (b) time and workload, (c) lack of
      administrative support and (d) lack of mentor's involvement. Strategies proposed
      were (a) building a knowledge base, (b) negotiation and dialogue and (c) self
      reliance and persistence. IMPLICATIONS: The ACPF program is an innovative and
      highly utilized initiative. While this program supports strategic directions of
      government and nursing professional groups, further research will validate and
      expand on the specific ways in which the initiative influences professional
      development, healthcare delivery and patient outcomes.

PMID- 24863581
TI  - Nurse practitioners and controlled substances prescriptive authority: improving
      access to care.
AB  - In 2007, Health Canada proposed a new framework to regulate prescriptive
      authority for controlled substances, titled New Classes of Practitioners
      Regulations (NCPR). The new regulatory framework was passed in November 2012; it
      gives nurse practitioners (NPs), midwives and podiatrists the authority to
      prescribe controlled medications under the Controlled Drugs and Substances Act.
      It is expected that authorizing NPs to write prescriptions for certain controlled
      substances commonly used in primary care will enhance flexibility and timeliness
      in primary care service delivery. Studies from the United States have shown
      positive outcomes in primary care access, decreased healthcare costs and the
      evolution and advancement of the NP role when prescriptive authority was expanded
      to include controlled substances. The purpose of this paper is to examine how
      NPs' prescriptive authority for controlled substances affects access to primary
      care and NP role development. Three key issues identified from the experience of
      one group of NPs in the United States (access to care, professional autonomy and
      prescriber knowledge) offer insight into the practice changes that may be
      anticipated for NPs in Canada now that they have acquired prescriptive authority
      for controlled substances. Recommendations are offered to assist nurse leaders
      and educators to best support NPs as they take on this new and important role
      responsibility. 

PMID- 24863582
TI  - Exploring the leadership role of the clinical nurse specialist on an inpatient
      palliative care consulting team.
AB  - Demand for palliative care services in Canada will increase owing to an aging
      population and the evolving role of palliative care in non-malignant illness.
      Increasing healthcare demands continue to shape the clinical nurse specialist
      (CNS) role, especially in the area of palliative care. Clinical nurse specialists
      bring specialized knowledge, skills and leadership to the clinical setting to
      enhance patient and family care. This paper highlights the clinical leadership
      role of the CNS as triage leader for a hospital-based palliative care consulting
      team. Changes to the team's referral and triage processes are emphasized as key
      improvements to team efficiency and timely access to care for patients and
      families. 

PMID- 24863583
TI  - High serum level of haptoglobin is associated with the response of 12 weeks
      methotrexate therapy in recent-onset rheumatoid arthritis patients.
AB  - BACKGROUND: We previously found, using microarray, haptoglobin (HP) expression
      signal was 5.1-fold increased in peripheral blood mononuclear cells (PBMCs) from
      methotrexate (MTX)-resistant rheumatoid arthritis (RA) patients. OBJECTIVES: To
      investigate whether serum levels of HP are associated with the response of 12
      weeks MTX therapy in recent-onset RA patients. METHODS: Sixty-nine active RA
      patients with recent onset (< 24 months) were treated with MTX. Clinical
      variables, levels of HP messenger RNA (mRNA) in PBMCs and HP serum levels were
      tested at week 0 and week 12. RESULTS: After 12 weeks of MTX treatment, 34.7% of
      RA patients were categorized as responders according to European League Against
      Rheumatism (EULAR) response criteria (Week 12 Disease Activity Score of 28 joints
      [DAS-28] <= 3.2 and decrease > 1.2) and all others (65.2%) were defined as non
      responders. The baseline HP mRNA in PBMCs from non-responders is significantly
      higher than those in responders (P < 0.05). Similar to mRNA expression, non
      responders showed significantly elevated serum HP levels at baseline (369.9 +/-
      159.8 mg/dL) compared to those in responders (255.3 +/- 143.9 mg/dL) (P = 0.01).
      Serum HP levels were decreased significantly from 255.3 +/- 143.9 mg/dL at
      baseline to 186.4 +/- 108.5 mg/dL at week 12 (P = 0.04) in responders, but
      remained at high levels in non-responders. CONCLUSIONS: High serum levels of HP
      at baseline are associated with inadequate response of 12 weeks MTX treatment in
      recent-onset RA patients. Further replication studies in larger samples are
      needed to validate HP as a potential predictive biomarker for response to MTX
      therapy in RA.

PMID- 24863585
TI  - ADHD subjects fail to suppress eye blinks and microsaccades while anticipating
      visual stimuli but recover with medication.
AB  - Oculomotor behavior and parameters are known to be affected by the allocation of
      attention and could potentially be used to investigate attention disorders. We
      explored the oculomotor markers of Attention-deficit/hyperactivity disorder
      (ADHD) that are involuntary and quantitative and that could be used to reveal the
      core-affected mechanisms, as well as be used for differential diagnosis. We
      recorded eye movements in a group of 22 ADHD-diagnosed patients with and without
      medication (methylphenidate) and in 22 control observers while performing the
      test of variables of attention (t.o.v.a.). We found that the average microsaccade
      and blink rates were higher in the ADHD group, especially in the time interval
      around stimulus onset. These rates increased monotonically over session time for
      both groups, but with significantly faster increments in the unmedicated ADHD
      group. With medication, the level and time course of the microsaccade rate were
      fully normalized to the control level, regardless of the time interval within
      trials. In contrast, the pupil diameter decreased over time within sessions and
      significantly increased above the control level with medication. We interpreted
      the suppression of microsaccades and eye blinks around the stimulus onset as
      reflecting a temporal anticipation mechanism for the transient allocation of
      attention, and their overall rates as inversely reflecting the level of arousal.
      We suggest that ADHD subjects fail to maintain sufficient levels of arousal
      during a simple and prolonged task, which limits their ability to dynamically
      allocate attention while anticipating visual stimuli. This impairment normalizes
      with medication and its oculomotor quantification could potentially be used for
      differential diagnosis. 

PMID- 24863586
TI  - Interfacial nanobubbles are leaky: permeability of the gas/water interface.
AB  - Currently there is no widespread agreement on an explanation for the stability of
      surface nanobubbles. One means by which several explanations can be
      differentiated is through the predictions they make about the degree of
      permeability of the gas-solution interface. Here we test the hypothesis that the
      gas-solution interface of surface nanobubbles is permeable by experimental
      measurements of the exchange of carbon dioxide. We present measurements by
      attenuated total reflection Fourier transform infrared (ATR-FTIR) and atomic
      force microscopy (AFM), demonstrating that the gas inside surface nanobubbles is
      not sealed inside the bubbles, but rather exchanges with the dissolved gas in the
      liquid phase. Such gas transfer is measurable by using the infrared active gas
      CO2. We find that bubbles formed in air-saturated water that is then perfused
      with CO2-saturated water give rise to distinctive gaseous CO2 signals in ATR-FTIR
      measurements. Also the CO2 gas inside nanobubbles quickly dissolves into the
      surrounding air-saturated water. AFM images before and after fluid exchange show
      that CO2 bubbles shrink upon exposure to air-equilibrated liquid but remain
      stable for hours. Also air bubbles in contact with CO2-saturated water increase
      in size and Ostwald ripening occurs more rapidly due to the relatively high gas
      solubility of CO2 in water. 

PMID- 24863587
TI  - High aspect ratio wrinkles via substrate prestretch.
AB  - A non-fractured, high aspect ratio wrinkled surface is successfully fabricated.
      Building upon recently developed models of the localization transition and the
      current knowledge of surface failures, the wrinkling mode is stabilized at high
      strain, doubling the accessible wrinkling aspect ratio to the currently reported
      value. This high aspect ratio surface provides significant promise for future
      wrinkle-based applications. 

PMID- 24863584
TI  - Simultaneous recording of mouse retinal ganglion cells during epiretinal or
      subretinal stimulation.
AB  - We compared response patterns and electrical receptive fields (ERF) of retinal
      ganglion cells (RGCs) during epiretinal and subretinal electrical stimulation of
      isolated mouse retina. Retinas were stimulated with an array of 3200
      independently controllable electrodes. Four response patterns were observed: a
      burst of activity immediately after stimulation (Type I cells, Vision Research
      (2008), 48, 1562-1568), delayed bursts beginning >25ms after stimulation (Type
      II), a combination of both (Type III), and inhibition of ongoing spike activity.
      Type I responses were produced more often by epiretinal than subretinal
      stimulation whereas delayed and inhibitory responses were evoked more frequently
      by subretinal stimulation. Response latencies were significantly shorter with
      epiretinal than subretinal stimulation. These data suggest that subretinal
      stimulation is more effective at activating intraretinal circuits than epiretinal
      stimulation. There was no significant difference in charge threshold between
      subretinal and epiretinal configurations. ERFs were defined by the stimulating
      array surface area that successfully stimulated spikes in an RGC. ERFs were
      complex in shape, similar to receptive fields mapped with light. ERF areas were
      significantly smaller with subretinal than epiretinal stimulation. This may
      reflect the greater distance between stimulating electrodes and RGCs in the
      subretinal configuration. ERFs for immediate and delayed responses mapped within
      the same Type III cells differed in shape and size, consistent with different
      sites and mechanisms for generating these two response types. 

PMID- 24863588
TI  - Epicardial fat, metabolic dysregulation, and cardiovascular risk: putting things
      together.

PMID- 24863589
TI  - Decision making between percutaneous coronary intervention or bypass surgery in
      multi-vessel coronary disease.

PMID- 24863590
TI  - Basis for the interpretation of noninferiority studies: considering the ROCKET
      AF, RE-LY, and ARISTOTLE studies.

PMID- 24863591
TI  - Epicardial adipose tissue is associated with visceral fat, metabolic syndrome,
      and insulin resistance in menopausal women.
AB  - INTRODUCTION AND OBJECTIVES: Epicardial adipose tissue has been associated with
      several obesity-related parameters and with insulin resistance. Echocardiographic
      assessment of this tissue is an easy and reliable marker of cardiometabolic risk.
      However, there are insufficient studies on the relationship between epicardial
      fat and insulin resistance during the postmenopausal period, when cardiovascular
      risk increases in women. The objective of this study was to examine the
      association between epicardial adipose tissue and visceral adipose tissue, waist
      circumference, body mass index, and insulin resistance in postmenopausal women.
      METHODS: A cross sectional study was conducted in 34 postmenopausal women with
      and without metabolic syndrome. All participants underwent a transthoracic
      echocardiogram and body composition analysis. RESULTS: A positive correlation was
      observed between epicardial fat and visceral adipose tissue, body mass index, and
      waist circumference. The values of these correlations of epicardial fat thickness
      overlying the aorta-right ventricle were r = 0.505 (P < .003), r = 0.545 (P <
      .001), and r = 0.515 (P < .003), respectively. Epicardial adipose tissue was
      higher in postmenopausal women with metabolic syndrome than in those without this
      syndrome (mean [standard deviation], 544.2 [122.9] vs 363.6 [162.3] mm(2); P =
      .03). CONCLUSIONS: Epicardial fat thickness measured by echocardiography was
      associated with visceral adipose tissue and other obesity parameters. Epicardial
      adipose tissue was higher in postmenopausal women with metabolic syndrome.
      Therefore, echocardiographic assessment of epicardial fat may be a simple and
      reliable marker of cardiovascular risk in postmenopausal women.

PMID- 24863593
TI  - Sedentary lifestyle and its relation to cardiovascular risk factors, insulin
      resistance and inflammatory profile.
AB  - INTRODUCTION AND OBJECTIVES: To analyze the association between sitting time and
      biomarkers of insulin resistance and inflammation in a sample of healthy male
      workers. METHODS: Cross-sectional study carried out in a sample of 929 volunteers
      belonging to the Aragon Workers' Health Study cohort. Sociodemographic,
      anthropometric, pharmacological and laboratory data were collected: lipids-total
      cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein
      cholesterol, triglycerides, apolipoproteins A-1 and B-100, lipoprotein (a)-,
      insulin resistance-glucose, glycated hemoglobin, homeostasis model assessment of
      insulin resistance, insulin, and triglyceride/high-density lipoprotein
      cholesterol ratio-, and inflammatory profile-C-reactive protein and leukocytes.
      Information on sitting time and physical activity was assessed using a
      questionnaire. Sedentary behavior was analyzed in terms of prevalences and
      medians, according to tertiles, using a multivariate model (crude and adjusted
      linear regression) with biomarkers of inflammation and insulin resistance.
      RESULTS: The most sedentary individuals had higher body mass index, greater waist
      circumference, and higher systolic blood pressure, with a significant upward
      trend in each tertile. Likewise, they had a worse lipid profile with a higher C
      reactive protein level, homeostasis model assessment of insulin resistance index,
      triglyceride/high-density lipoprotein cholesterol ratio, and insulin
      concentration. In the multivariate analysis, we observed a significant
      association between the latter parameters and sitting time in hours (log C
      reactive protein [beta = 0.07], log homeostasis model assessment of insulin
      resistance index [beta = 0.05], triglyceride/high-density lipoprotein cholesterol
      ratio [beta = 0.23], and insulin [beta = 0.44]), which remained after adjustment
      for metabolic equivalents-h/week. CONCLUSIONS: Workers who spend more time
      sitting show a worse inflammatory and insulin resistance profile independently of
      the physical activity performed.

PMID- 24863592
TI  - Prevalence of obesity, diabetes and other cardiovascular risk factors in
      Andalusia (southern Spain). Comparison with national prevalence data. The
      Di@bet.es study.
AB  - INTRODUCTION AND OBJECTIVES: The aim of this study was to compare the prevalences
      of obesity, diabetes and other cardiovascular risk factors in the region of
      Andalusia with those in the rest of Spain. METHODS: The Di@bet.es study is a
      national, cross-sectional, population-based survey of cardiometabolic risk
      factors and their association with lifestyle. The sample consisted of 5103
      participants >= 18 years. The variables analyzed were clinical, demographic and
      lifestyle survey, physical examination, and oral glucose tolerance test. The
      prevalence of cardiovascular risk factors in Andalusia (n=1517) was compared with
      that for the rest of Spain (n=3586). RESULTS: In data adjusted to the Spanish
      population, the prevalence of diabetes (World Health Organization, 1999),
      hypertension (blood pressure >= 140/90 mmHg), high-sensitivity CRP levels (>= 3
      mg/L) and obesity (body mass index >= 30 kg/m(2)) were 16.3%, 43.9%, 32.0%, and
      37.0% in Andalusia compared with 12.5%, 39.9%, 28.3%, and 26.6% in the rest of
      Spain (P<.001 for differences except P=.01 for the difference in high-sensitivity
      CRP levels). The corresponding figures for the Andalusia data adjusted to the
      Andalusian population were 15.3%, 42.3%, 31.4%, and 34.0%, respectively.
      Differences in diabetes, hypertension and high-sensitivity CRP were not
      significant in models adjusted for age, sex, and adiposity measurements.
      Differences in obesity were not significant in models adjusted for age, sex,
      educational level, marital status, work status, and physical activity (P=.086)
      CONCLUSIONS: This study contributes information from a national study perspective
      and shows a higher prevalence of cardiovascular risk factors in southern Spain,
      in close relation to obesity, a sedentary lifestyle, and markers of socioeconomic
      disadvantage.

PMID- 24863594
TI  - Safety and efficacy of different paclitaxel-eluting balloons in a porcine model.
AB  - INTRODUCTION AND OBJECTIVES: Paclitaxel-eluting balloons have shown high
      antiproliferative efficacy in the treatment and prevention of restenosis.
      Nevertheless, not all available devices are equally effective, which makes it
      interesting to compare results in a preclinical model. Our objective was to
      assess the preclinical efficacy and safety of different devices. METHODS: We
      implanted 51 metallic stents (Architect((r)), iVascular) in 17 domestic swine
      (mean, 25 [3] kg), inserting 1 stent per major coronary artery. Stent
      postdilatation was performed with different control balloons (n=10) or paclitaxel
      eluting balloons: paclitaxel-eluting balloon 1 (iVascular) (n=15); paclitaxel
      eluting balloon 2 (iVascular) (n=16) and In.Pact Falcon((r)) (Medtronic) (n=10).
      The restenosis rate (using angiography and histomorphometry) and vascular healing
      parameters (balloon-related vascular injury score, endothelialization rate, and
      fibrin and inflammation scores) were analyzed at 28 days. RESULTS: The distinct
      paclitaxel-eluting balloons showed a similar degree of stenosis at follow-up,
      which was significantly lower than that in the control group: diameter stenosis
      was 9% (12%) vs 34% (18%) by angiography (P<.0001) and was 22% (8%) vs 51% (18%)
      by histomorphometry (P<.0001). Scores for vascular injury (mean, 0.6 [0.5]) and
      inflammation (mean, 0.8 [0.3]) were uniformly low across all groups. Drug effect
      markers differed significantly between the paclitaxel-eluting balloons and
      control groups, with lower endothelialization rates (87% [10%] vs 99% [2%];
      P=.0007) and higher fibrin scores (2.1 [0.7] vs 0.4 [0.5]; P<.0001) in the
      paclitaxel-eluting balloons groups. There were no differences between the
      different paclitaxel-eluting balloons. CONCLUSIONS: In this preclinical model,
      the paclitaxel-eluting balloons studied significantly reduced in-stent restenosis
      compared with the control balloons. Although there were no findings of persistent
      vascular injury or inflammation, delayed endothelialization and fibrin aggregate
      suggest a drug deposition response.

PMID- 24863595
TI  - Efficacy of bleeding risk scores in elderly patients with acute coronary
      syndromes.
AB  - INTRODUCTION AND OBJECTIVES: The incidence of acute coronary syndromes is high in
      the elderly population. Bleeding is associated with a poorer prognosis in this
      clinical setting. The available bleeding risk scores have not been validated
      specifically in the elderly. Our aim was to assess predictive ability of the most
      important bleeding risk scores in patients with acute coronary syndrome aged >=
      75 years. METHODS: We prospectively included consecutive acute coronary syndromes
      patients. Baseline characteristics, laboratory findings, and hemodynamic data
      were collected. In-hospital bleeding was defined according to CRUSADE, Mehran,
      ACTION, and BARC definitions. CRUSADE, Mehran, and ACTION bleeding risk scores
      were calculated for each patient. The ability of these scores to predict major
      bleeding was assessed by binary logistic regression, receiver operating
      characteristic curves, and area under the curves. RESULTS: We included 2036
      patients, with mean age of 62.1 years; 369 patients (18.1%) were >= 75 years.
      Older patients had higher bleeding risk (CRUSADE, 42 vs 22; Mehran, 25 vs 15;
      ACTION, 36 vs 28; P<.001) and a slightly higher incidence of major bleeding
      events (CRUSADE bleeding, 5.1% vs 3.8%; P=.250). The predictive ability of these
      3 scores was lower in the elderly (area under the curve, CRUSADE: 0.63 in older
      patients, 0.81 in young patients; P=.027; Mehran: 0.67 in older patients, 0.73 in
      younger patients; P=.340; ACTION: 0.58 in older patients, 0.75 in younger
      patients; P=.041). CONCLUSIONS: Current bleeding risk scores showed poorer
      predictive performance in elderly patients with acute coronary syndromes than in
      younger patients.

PMID- 24863596
TI  - Impact of previous vascular burden on in-hospital and long-term mortality in
      patients with ST-segment elevation myocardial infarction.
AB  - INTRODUCTION AND OBJECTIVES: Patients with a current acute coronary syndrome and
      previous ischemic heart disease, peripheral arterial disease, and/or
      cerebrovascular disease are reported to have a poorer outcome than those without
      these previous conditions. It is uncertain whether this association with outcome
      is observed at long-term follow-up. METHODS: Prospective observational study,
      including 4247 patients with ST-segment elevation myocardial infarction. Detailed
      clinical data and information on previous ischemic heart disease, peripheral
      arterial disease, and cerebrovascular disease ("vascular burden") were recorded.
      Multivariate models were performed for in-hospital and long-term (median, 7.2
      years) all-cause mortality. RESULTS: One vascular territory was affected in 1131
      (26.6%) patients and >= 2 territories in 221 (5.2%). The total in-hospital
      mortality rate was 12.3% and the long-term incidence density was 3.5 deaths per
      100 patient-years. A background of previous ischemic heart disease (odds ratio =
      0.83; P = .35), peripheral arterial disease (odds ratio = 1.30; P = .34), or
      cerebrovascular disease (stroke) (odds ratio = 1.15; P = .59) was not
      independently predictive of in-hospital death. In an adjusted model, previous
      cerebrovascular disease and previous peripheral arterial disease were both
      predictors of mortality at long-term follow-up (hazard ratio = 1.57; P < .001;
      and hazard ratio = 1.34; P = .001; respectively). Patients with >= 2 diseased
      vascular territories showed higher long-term mortality (hazard ratio = 2.35; P <
      .001), but not higher in-hospital mortality (odds ratio = 1.07; P = .844).
      CONCLUSIONS: In patients with a diagnosis of ST-segment elevation acute
      myocardial infarction, the previous vascular burden determines greater long-term
      mortality. Considered individually, previous cerebrovascular disease and
      peripheral arterial disease were predictors of mortality at long-term after
      hospital discharge.

PMID- 24863597
TI  - Update: Acute coronary syndromes (V). Personalized antiplatelet therapy.
AB  - It is well established that high on-treatment platelet reactivity to adenosine
      diphosphate during clopidogrel therapy is an independent risk factor for ischemic
      event occurrences in a postpercutaneous coronary intervention patients. However,
      the precise role of platelet function testing remains debated. Platelet function
      testing to ensure optimal platelet inhibition has been recommended by some
      authorities to improve outcomes in patients treated with clopidogrel. Recent
      prospective, randomized trials of personalized antiplatelet therapy have failed
      to demonstrate a benefit of platelet function testing in improving outcomes. In
      this review article, we discuss the mechanisms responsible for clopidogrel
      nonreponsiveness, recent trials of platelet function testing, and other new
      developments in the field of personalized antiplatelet therapy. 

PMID- 24863598
TI  - New quantitative model of aortic valve in PreTAVI patients.

PMID- 24863599
TI  - Giant coronary aneurysms in Kawasaki disease.

PMID- 24863600
TI  - Coronary arteriovenous fistula secondary to iatrogenic coronary perforation.

PMID- 24863601
TI  - Stent implantation in the anastomosis after correction of a total anomalous
      pulmonary venous connection.

PMID- 24863602
TI  - Percutaneous closure of VSD and TAVI with left atrial appendage exclusion in a
      single procedure: potential benefits of a combined structural interventional
      procedure.

PMID- 24863603
TI  - Desensitization to acetylsalicylic acid in patients undergoing percutaneous
      coronary intervention. Experience in a tertiary center.

PMID- 24863604
TI  - Inappropriate defibrillator shock in a subcutaneous device secondary to
      repetitive muscle contractions.

PMID- 24863605
TI  - New data about atrial fibrillation, comment to the OFRECE study. Response.

PMID- 24863607
TI  - Specific modeling and quantification of the aortic valve.

PMID- 24863606
TI  - New data about atrial fibrillation, comment to the OFRECE study.

PMID- 24863608
TI  - Specific modeling and quantification of the aortic valve. Response.

PMID- 24863609
TI  - Acute shock dengue myocarditis.

PMID- 24863610
TI  - Acute shock dengue myocarditis. Response.

PMID- 24863612
TI  - Role of protease maturation lipoprotein in osmoadaptation of Streptococcus
      mutans.
AB  - Osmoadaptation may be an important trait for the pathogenicity of Streptococcus
      mutans. However, how this organism adapts to changes in osmolality in the oral
      cavity remains unclear. In this study, we showed that S. mutans utilizes K(+) for
      osmoadaptation, in which protease maturation lipoprotein (PrtM) plays an
      important role. Although growth of the wild-type strain was impaired in a
      hyperosmotic medium [brain heart infusion (BHI) containing 0.3 M NaCl] compared
      with that in an unmodified BHI, the prtM mutant grew much more poorly in 0.3 M
      NaCl BHI. Comparison of growth behavior in the hyperosmotic medium supplemented
      with different osmoprotectants revealed that only the addition of K(+) allowed
      the bacteria to overcome the impairment of growth caused by the high osmolality.
      These results suggest that K(+) is an important compatible solute for S. mutans.
      Moreover, K(+) -associated recovery of growth was not observed for the prtM
      mutant, indicating that PrtM plays a critical role in the utilization of K(+) .
      Quantitative reverse-transcriptase polymerase chain reaction analysis showed that
      prtM was induced by osmotic stress, implying that prtM is an osmoresponsive gene.
      These findings suggest that K(+) is an important compatible solute for S. mutans,
      and that the osmoresponsive lipoprotein PrtM is involved in K(+) utilization,
      contributing to osmoadaptation of S. mutans.

PMID- 24863613
TI  - Highly efficient expression and characterization of a beta-mannanase from
      Bacillus subtilis in Pichia pastoris.
AB  - A beta-mannanase gene (Man5) from Bacillus subtilis BS5 was cloned by PCR and
      integrated into the genome of Pichia pastoris GS115 via pPIC9 vector. The
      recombinant Man5 with a molecular mass of 43 kDa was successfully expressed and
      secreted into the culture medium. After methanol induction in a shake flask for
      96 H, the recombinant Man5 protein reached 375 ug/mL in concentration, with an
      enzyme activity of 892 U/mL. The recombinant Man5 was purified 3.35-fold with 60%
      yield by using HiTrap DEAE FF and HiTrap Phenyl FF columns. The specific activity
      of the purified enzyme was 7,978 U/mg. The optimum temperature and pH of the
      recombinant Man5 were 50  degrees C and 6.0, respectively. Studies of substrate
      specificity showed that the optimum substrate for the Man5 was konjac flour,
      suggesting that it has great potential as an effective additive in the food
      industry. 

PMID- 24863614
TI  - Raw coffee based dietary supplements contain carboxyatractyligenin derivatives
      inhibiting mitochondrial adenine-nucleotide-translocase.
AB  - Capsules, powders and tablets containing raw coffee extract are advertised to the
      consumer as antioxidant rich dietary supplements as part of a healthy diet. We
      isolated carboxyatractyligenin (4), 2-O-beta-d-glucopyranosyl
      carboxyatractyligenin (6) and 3'-O-beta-d-glucopyranosyl-2'-O-isovaleryl-2beta-(2
      desoxy-carboxyatractyligenin)-beta-d-glucopyranoside (8) from green coffee and
      found strong inhibitory effects on phosphorylating respiration in isolated
      mitochondria similar to the effects of the known phytotoxin carboxyatractyloside.
      LC-MS/MS analysis of commercial green coffee based dietary supplements revealed
      the occurrence of carboxyatractyligenin, 3'-O-beta-d-glucopyranosyl-2'-O
      isovaleryl-2beta-(2-desoxy-carboxyatractyligenin)-beta-d-glucopyranoside, and 2-O
      beta-d-glucopyranosyl carboxyatractyligenin in concentrations up to 4.0, 5.7, and
      41.6MUmol/g, respectively. These data might help to gain first insight into
      potential physiological side-effects of green coffee containing dietary
      supplement. 

PMID- 24863616
TI  - [Low-grade gliomas: review of 10 years].
AB  - INTRODUCTION: Central nervous system (CNS) tumors are the most common solid
      tumors in children. Among these, the low-grade gliomas are the most common type,
      accounting for up to 30-50% of them. PATIENTS AND METHODS: A retrospective
      analysis was carried out on the epidemiology, clinical characteristics, tumor
      location, histology, treatment, outcome and long-term sequelae of 111 patients
      diagnosed with low-grade glioma in the Nino Jesus Children's Hospital of Madrid
      from January 2002 to December 2011. RESULTS: Of the 111 patients, there were 57
      boys and 54 girls. The mean age was 7.26 years (range, 2 months - 19 years). The
      most common symptoms of presentation were headache (27%) and vomiting (19%). The
      most common locations were the cerebral hemispheres (38%), followed by the
      brainstem (27.4%), and cerebellum (18.5%). Histological examination was performed
      in 89 patients (80.18%). Pilocytic astrocytoma was the most common histological
      type. Diagnostic biopsy was performed in 20 patients (22.5%), partial resection
      in 38 patients (42.7%), and total resection in 31 patients (34.8%). Sixteen
      patients received chemotherapy (14%), and eighteen patients received radiotherapy
      (16%). Overall survival was 88.3%. Long term hearing, visual and endocrine
      sequelae were note in 1, 5, and 4 patients, respectively. CONCLUSIONS: The most
      common histological type is pilocytic astrocytoma. Overall survival was 88.3%.
      Only 9% of patients had some kind or auditory, visual or endocrine sequelae.

PMID- 24863617
TI  - [Congenital tumor of tongue].

PMID- 24863615
TI  - Temporal trends in the use of high-dose potent statins following acute coronary
      syndrome in Israel.
AB  - OBJECTIVES: This study aimed to evaluate factors associated with the prescription
      of high-dose potent statin (HDPS) therapy following hospitalization for acute
      coronary events. STUDY DESIGN: Sub-analysis was made using the data of 3,525
      patients enrolled in the 2008 and 2010 Acute Coronary Syndrome Israeli Surveys
      (ACSIS). METHODS: Analyses were carried out to identify demographic and clinical
      factors associated with the prescription of HDPS therapy (atorvastatin 40-80
      mg/day or rosuvastatin 20-40 mg/day) at discharge compared with the prescription
      of lower-dose statins. RESULTS: Among the study patients, 1,387 (39%) were
      discharged on HDPS, 1,860 (53%) with lower-dose statin regimens and 278 (8%) with
      no recommendation for statin therapy. Multivariate logistic regression analysis
      showed that pre-admission usage of HDPS and participation in the more recent
      (2010) ACSIS survey were independently associated with a higher likelihood of
      HDPS prescription at discharge from the index event (odds ratio, OR, 21.07, p <
      0.001, and 5.61, p < 0.001, respectively), whereas factors independently
      associated with a lack of HDPS prescription included age >75 years (OR 0.76, p =
      0.03), low-density lipoprotein-cholesterol levels <100 mg/dl on admission (OR
      0.67, p < 0.001) and a history of heart failure prior to the index
      hospitalization (OR 0.54, p = 0.0018). The 30-day compliance with the HDPS
      regimen was 98%. CONCLUSIONS: The findings show increased use of HDPS therapy in
      acute coronary syndrome (ACS) patients, although this mode of medical therapy is
      still underutilized in the important subset of high-risk ACS patients.

PMID- 24863618
TI  - [Factors related to dissatisfaction and anger in parents of children treated at
      paediatric emergency services].
AB  - AIM: Anger in patients and relatives is very frequent in health emergency
      services and is often associated with aggressiveness and emotional alterations.
      The aim of the present study is to explore anger in parents while their children
      are receiving care in paediatric emergency services, seeking the specific
      dimensions of dissatisfaction that may predict the onset of anger in parents.
      MATERIALS AND METHODS: A cross-sectional descriptive study using a self-report
      questionnaire in 711 parents of children seen in paediatric emergency
      departments. The self-report questionnaires used were the State-Trait Anger
      Expression Inventory-2 (STAXI-2) and the Satisfaction with Healthcare Services
      Scale. The statistical analysis included descriptive, correlational, variance and
      multiple linear regression models. RESULTS: A total of 53 parents (7,5%) showed a
      moderate or high anger level. The mean score for satisfaction was 37.12
      (SD=7.33). It was found that higher levels of overall satisfaction were
      significantly associated with lower levels of anger (r=-.29, p=.00). Among the
      variables studied, dissatisfaction with access to the service (beta=-.172,
      p=.00), with the healthcare staff (beta=-.121, p=.01), and perceived severity of
      the child's health status (beta=.157, p=.00) predicted higher levels of anger.
      CONCLUSIONS: On the basis of our results, it is important to continue working to
      substantially improve access for patients and their families to the emergency
      department, as well as the information and communication process with the
      healthcare staff should be included in intervention initiatives.

PMID- 24863619
TI  - Detection and molecular cloning of CYP74Q1 gene: identification of Ranunculus
      acris leaf divinyl ether synthase.
AB  - Enzymes of the CYP74 family, including the divinyl ether synthase (DES), play
      important roles in plant cell signalling and defence. The potent DES activities
      have been detected before in the leaves of the meadow buttercup (Ranunculus acris
      L.) and few other Ranunculaceae species. The nature of these DESs and their genes
      remained unrevealed. The PCR with degenerate primers enabled to detect the
      transcript of unknown P450 gene assigned as CYP74Q1. Besides, two more CYP74Q1
      isoforms with minimal sequence variations have been found. The full length
      recombinant CYP74Q1 protein was expressed in Escherichia coli. The preferred
      substrates of this enzyme are the 13-hydroperoxides of alpha-linolenic and
      linoleic acids, which are converted to the divinyl ether oxylipins (omega5Z)
      etherolenic acid, (9Z,11E)-12-[(1'Z,3'Z)-hexadienyloxy]-9,11-dodecadienoic acid,
      and (omega5Z)-etheroleic acid, (9Z,11E)-12-[(1'Z)-hexenyloxy]-9,11-dodecadienoic
      acid, respectively, as revealed by the data of mass spectrometry, NMR and UV
      spectroscopy. Thus, CYP74Q1 protein was identified as the R. acris DES (RaDES), a
      novel DES type and the opening member of new CYP74Q subfamily. 

PMID- 24863620
TI  - Neurokinin B receptor antagonism decreases luteinising hormone pulse frequency
      and amplitude and delays puberty onset in the female rat.
AB  - The neural mechanisms controlling puberty onset remain enigmatic. Humans with
      loss of function mutations in TAC3 or TACR3, the genes encoding neurokinin B
      (NKB) or its receptor, neurokinin-3 receptor (NK3R), respectively, present with
      severe congenital gonadotrophin deficiency and pubertal failure. Animal studies
      have shown ambiguous actions of NKB-NK3R signalling with respect to controlling
      puberty onset. The present study aimed to determine the role of endogenous NKB
      NK3R signalling in the control of pulsatile luteinising hormone (LH) secretion
      and the timing of puberty onset, and also whether precocious pubertal onset as a
      result of an obesogenic diet is similarly regulated by this neuropeptide system.
      Prepubertal female rats, chronically implanted with i.c.v. cannulae, were
      administered SB222200, a NK3R antagonist, or artificial cerebrospinal fluid via
      an osmotic mini-pump for 14 days. SB222200 significantly delayed the onset of
      vaginal opening and first oestrus (as markers of puberty) compared to controls in
      both normal and high-fat diet fed animals. Additionally, serial blood sampling,
      via chronic indwelling cardiac catheters, revealed that the increase in LH pulse
      frequency was delayed and that the LH pulse amplitude was reduced in response to
      NK3R antagonism, regardless of dietary status. These data suggest that endogenous
      NKB-NK3R signalling plays a role in controlling the timing of puberty and the
      associated acceleration of gonadotrophin-releasing hormone pulse generator
      frequency in the female rat.

PMID- 24863621
TI  - Formation of gas-phase peptide ions and their dissociation in MALDI: insights
      from kinetic and ion yield studies.
AB  - Insights on mechanisms for the generation of gas-phase peptide ions and their
      dissociation in matrix-assisted laser desorption ionization (MALDI) gained from
      the kinetic and ion yield studies are presented. Even though the time-resolved
      photodissociation technique was initially used to determine the dissociation
      kinetics of peptide ions and their effective temperature, it was replaced by a
      simpler method utilizing dissociation yields from in-source decay (ISD) and post
      source decay (PSD). The ion yields for a matrix and a peptide were measured by
      repeatedly irradiating a region on a sample and collecting ion signals until the
      sample in the region was completely depleted. Matrix- and peptide-derived gas
      phase cations were found to be generated by pre-formed ion emission or by ion
      pair emission followed by anion loss, but not by laser-induced ionization. The
      total number of ions, that is, matrix plus peptide, was found to be equal to the
      number of ions emitted from a pure matrix. A matrix plume was found to cool as it
      expanded, from around 800-1,000 K to 400-500 K. Dissociation of peptide ions
      along b/y channels was found to occur statistically, that is, following RRKM
      behavior. Small critical energy (E0  = 0.6-0.7 eV) and highly negative critical
      entropy (DeltaS(?)  = -30 to -25 eu) suggested that the transition structure was
      stabilized by multiple intramolecular interactions.

PMID- 24863622
TI  - Spectrum of chronic liver disease admitted to a medical college hospital in
      northern India: is there cause for concern?

PMID- 24863623
TI  - Influenza A/H1/N1/09 infection in cirrhosis.

PMID- 24863624
TI  - Statistical analysis in MSW collection performance assessment.
AB  - The increase of Municipal Solid Waste (MSW) generated over the last years forces
      waste managers pursuing more effective collection schemes, technically viable,
      environmentally effective and economically sustainable. The assessment of MSW
      services using performance indicators plays a crucial role for improving service
      quality. In this work, we focus on the relevance of regular system monitoring as
      a service assessment tool. In particular, we select and test a core-set of MSW
      collection performance indicators (effective collection distance, effective
      collection time and effective fuel consumption) that highlights collection system
      strengths and weaknesses and supports pro-active management decision-making and
      strategic planning. A statistical analysis was conducted with data collected in
      mixed collection system of Oporto Municipality, Portugal, during one year, a week
      per month. This analysis provides collection circuits' operational assessment and
      supports effective short-term municipality collection strategies at the level of,
      e.g., collection frequency and timetables, and type of containers. 

PMID- 24863625
TI  - CFD simulation of MSW combustion and SNCR in a commercial incinerator.
AB  - A CFD scheme was presented for modeling municipal solid waste (MSW) combustion in
      a moving-grate incinerator, including the in-bed burning of solid wastes, the out
      of-bed burnout of gaseous volatiles, and the selective non-catalytic reduction
      (SNCR) process between urea (CO(NH2)2) and NOx. The in-bed calculations provided
      2-D profiles of the gas-solid temperatures and the gas species concentrations
      along the bed length, which were then used as inlet conditions for the out-of-bed
      computations. The over-bed simulations provided the profiles of incident
      radiation heat flux on the top of bed. A 3-dimensional benchmark simulation was
      conducted with a 750 t/day commercial incinerator using the present coupling
      scheme incorporating with a reduced SNCR reduction mechanism. Numerical tests
      were performed to investigate the effects of operating parameters such as
      injection position, injection speed and the normalized stoichiometric ratio (NSR)
      on the SNCR performance. The simulation results showed that the distributions of
      gas velocity, temperature and NOx concentration were highly non-uniform, which
      made the injection position one of the most sensitive operating parameters
      influencing the SNCR performance of moving grate incinerators. The simulation
      results also showed that multi-layer injections were needed to meet the EU2000
      standard, and a NSR 1.5 was suggested as a compromise of a satisfactory NOx
      reduction and reasonable NH3 slip rates. This work provided useful guides to the
      design and operation of SNCR process in moving-grate incinerators.

PMID- 24863626
TI  - Characteristics of element distributions in an MSW ash melting treatment system.
AB  - Thermal treatment of municipal solid waste (MSW) has become a common practice in
      waste volume reduction and resource recovery. For the utilization of molten slag
      for construction materials and metal recovery, it is important to understand the
      behavior of heavy metals in the melting process. In this study, the correlation
      between the contents of elements in feed materials and MSW molten slag and their
      distributions in the ash melting process, including metal residues, are
      investigated. The hazardous metal contents in the molten slag were significantly
      related to the contents of metals in the feed materials. Therefore, the
      separation of products containing these metals in waste materials could be an
      effective means of producing environmentally safe molten slag with a low
      hazardous metals content. The distribution ratios of elements in the ash melting
      process were also determined. The elements Zn and Pb were found to have a
      distribution ratio of over 60% in fly ash from the melting furnace and the
      contents of these metals were also high; therefore, Zn and Pb could be potential
      target metals for recycling from fly ash from the melting furnace. Meanwhile, Cu,
      Ni, Mo, Sn, and Sb were found to have distribution ratios of over 60% in the
      metal residue. Therefore, metal residue could be a good resource for these
      metals, as the contents of Cu, Ni, Mo, Sn, and Sb in metal residue are higher
      than those in other output materials. 

PMID- 24863628
TI  - Characteristic and potential sources of polychlorinated dibenzo-P-dioxins and
      dibenzofurans in agricultural soils in Beijing, China.
AB  - Polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) were analyzed in 25
      background and 80 agricultural soil samples collected from 21 sites in Beijing,
      China. The levels of PCDD/Fs in the north agricultural soils were low (0.15-0.58
      ng international toxic equivalent quantity [I-TEQ]/kg), which were comparable
      with those of the background soils (0.091-0.35 ng I-TEQ/kg). In the southern
      agricultural soils, however, concentrations were several times higher (0.27-3.3
      ng I-TEQ/kg). Comparison of PCDD/Fs congener compositions between possible
      sources and samples indicated that agricultural soils in Beijing had not been
      contaminated by the 3 main PCDD/F contamination sources in China--ferrous and
      nonferrous metal, waste incineration, and power generation. They had, however,
      been slightly contaminated by the impurities of some organochlorine pesticides,
      such as sodium pentachlorophenate, and by open burning of biomass, vehicle
      exhaust, atmospheric deposition, sediment, and sewage sludge. These results have
      been supported by the principal components analysis.

PMID- 24863627
TI  - Compulsivity and Impulsivity in Pathological Gambling: Does a Dimensional
      Transdiagnostic Approach Add Clinical Utility to DSM-5 Classification?
AB  - Although the phenomenology of Pathological Gambling (PG) is clearly characterized
      by impulsive features, some of the Diagnostic and Statistical Manual of Mental
      Disorder (DSM-5) criteria for PG are similar to those of Obsessive Compulsive
      Disorder (OCD). Therefore, the compulsive-impulsive spectrum model may be a
      better (or complementary) fit with PG phenomenology. The present exploratory
      research was designed to further investigate the compulsive and impulsive
      features characterizing PG, by comparing PG individuals, alcohol dependents
      (ADs), OCD patients, and healthy controls (HCs) on both self-report and cognitive
      measures of compulsivity and impulsivity. A better understanding of the shared
      psychological and cognitive mechanisms underlying differently categorized
      compulsive and impulsive disorders may significantly impact on both clinical
      assessment and treatment strategies for PG patients. With respect to self-report
      measures, PG individuals reported more compulsive and impulsive features than did
      HCs. As regards motor inhibition ability indices, PG individuals and HCs
      performed similarly on the Go/No-go task and better than AD individuals and OCD
      patients. Results from the Iowa Gambling Task highlighted that PG, AD, and OCD
      participants performed worse than did HCs. An in-depth analysis of each group's
      learning profile revealed similar patterns of impairment between PG and AD
      individuals in decision-making processes. Current findings support the utility of
      adopting a dimensional-transdiagnostic approach to complement the DSM-5
      classification when working with PG individuals in clinical practice. Indeed,
      clinicians are encouraged to assess both compulsivity and impulsivity to provide
      individualized case conceptualizations and treatment plans focusing on the
      specific phenomenological features characterizing each PG patient. 

PMID- 24863629
TI  - Convergence in findings from randomized trials and elaborately analysed
      observational data on mortality reduction with carvedilol in heart failure in
      comparison with metoprolol.

PMID- 24863630
TI  - The undivided patient: a retrospective cohort analysis of specialty referrals
      made from inpatient general medical units comparing regional to metropolitan
      practice.
AB  - BACKGROUND: In an era of growing subspecialisation there has been significant
      research into the role, determinants and outcomes of outpatient referrals but
      very little on inpatient specialty referrals from general medical units. AIMS:
      This study aims to describe and compare the rate of specialty referrals from
      inpatient general medical units in a regional general and a metropolitan tertiary
      hospital, and review associated outcomes. METHODS: Retrospective cohort analysis
      of general medical admissions over the 10-week period extending from 28 March to
      5 June 2011. Two hospitals were included in the study; West Gippsland Hospital
      (WGH) and Monash Medical Centre (MMC). For all admissions, details of patient
      demographics, episode of care and number of inpatient referrals made per
      admission were extracted from the medical records. Rates and outcomes of
      inpatient referrals were calculated and compared. RESULTS: There were 116
      admissions to MMC and 108 (107 available for analysis) to WGH during the study
      period. There were no significant differences in patient demographics between the
      two sites. However, there were significantly fewer active conditions (2.87 vs
      4.01, P < 0.01), fewer specialty fields represented (2.50 vs 3.51, P < 0.01) and
      fewer specialty referrals made per admission at WGH compared with MMC (0.69 vs
      1.74, P < 0.01). The referral rate per diagnosis and the rate of referrals per
      specialty field represented were significantly higher at MMC compared with WGH (P
      < 0.01). CONCLUSION: This preliminary study suggests that patients admitted to
      rural hospital general medical units have fewer active conditions with fewer
      specialty referrals made per admission, compared with a comparator metropolitan
      hospital general medical unit. Further research is required to investigate the
      reasons for such differences and implications for policy and practice.

PMID- 24863632
TI  - Mutation in the X-linked RAB40AL gene (Martin-Probst syndrome) with mental
      retardation, sensorineural hearing loss, and anomalies of the craniofacies and
      genitourinary tract: a second case report.
AB  - An X-linked neurodevelopmental disorder previously had been reported in only one
      family, associated with a p.D59G mutation in the RAB40AL gene that encodes a
      mitochondrial Ras protein. The three related males described had varying degrees
      of cognitive impairment, sensorineural hearing loss, short stature, dysmorphic
      facies, and other morphological defects. CONCLUSION: We herein present an
      unrelated 20-year-old male with similar manifestations also with p.D59G in the
      RAB40AL gene, which supports the existence of this condition previously coined as
      Martin-Probst syndrome (OMIM: 300519).

PMID- 24863631
TI  - The influence of cardiopulmonary bypass priming without FFP on postoperative
      coagulation and recovery in pediatric patients with cyanotic congenital heart
      disease.
AB  - Transfusion guidelines have been produced for the evidence-based use of fresh
      frozen plasma (FFP). However, the inappropriate use of FFP is still a worldwide
      problem, especially in the prophylactic settings. In the present study, 100
      cyanotic pediatric patients (age 6 months to 3 years) undergoing cardiac surgery
      with cardiopulmonary bypass (CPB) were randomized to receive either 10-20 ml/kg
      FFP (FFP group, n = 50) or 10-20 ml/kg 4 % succinylated gelatin (Gelofusine, GEL
      group, n = 50) in the priming solution. Rapid thromboelastography (r-TEG) was
      measured before skin incision and 15 min after heparin neutralization.
      Postoperative renal and hepatic function, mediastinal chest tube drainage,
      transfusion requirements, and recovery time were observed. The relationships
      between hematologic and demographic data and postoperative bleeding volume were
      also analyzed. The results showed that there were significantly elevated levels
      of fibrinogen (r-TEG parameters: fibrinogen contribution to maximal amplitude
      (MAf) and fibrinogen level (FLEV)) in the FFP group compared to the GEL group.
      The postoperative blood loss, total transfusion requirements, and recovery time
      were not significantly different between the two groups, indicating that there
      were no obvious clinical benefits of using FFP in the priming. The maximal
      amplitude (MA) of r-TEG measured after heparin neutralization was correlated with
      the 6-h postoperative bleeding volume. In addition, preoperative fibrinogen level
      rather than FFP priming was an independent predictor of postoperative blood loss.
      CONCLUSION: Prophylactic use of FFP in the priming solution does not have obvious
      clinical benefits in cyanotic congenital heart disease (CCHD) patients.
      Gelofusine, an artificial colloid, is a safe and effective substitute of FFP in
      the priming solution. Furthermore, r-TEG can be used as a "real-time" assessment
      tool to evaluate postoperative bleeding and guide transfusion after cardiac
      surgery in pediatric patients.

PMID- 24863633
TI  - Acute funisitis is associated with distinct changes in fetal hematologic profile.
AB  - OBJECTIVE: Acute funisitis is a histologic hallmark of the fetal inflammatory
      response syndrome. This study was conducted to examine the hematologic profiles
      of preterm newborns with funisitis. METHODS: The hematologic profiles of
      umbilical cord blood obtained at birth were compared according to the presence or
      absence of acute funisitis in 197 preterm neonates (gestational age before 34
      weeks) born to mothers with preterm labor with intact membranes or premature
      rupture of membranes. RESULTS: (1) Funisitis was identified in 22.3% (44/197) of
      patients; (2) newborns with funisitis had higher median leukocyte, neutrophil,
      monocyte counts (p < 0.005 for each), higher rate of neutrophilia (p < 0.05),
      higher proportion of neutrophils among leukocytes and lower proportion of
      lymphocytes among leukocytes than those without funisitis (p < 0.01 for each);
      (3) newborns with funisitis had a significantly lower median RBC count,
      hemoglobin concentration and hematocrit than those without funisitis (p < 0.05
      for each); (4) there was no significant difference in the median lymphocyte,
      eosinophil, basophil, NRBC and platelet counts between the two groups (p > 0.1
      for each). CONCLUSIONS: The hematologic profiles of preterm newborns with
      funisitis are characterized by increased total white blood cell, neutrophil, and
      monocyte counts and decreased RBC count and hemoglobin concentration.

PMID- 24863634
TI  - Does artificial rupturing of membranes in the active phase of labor enhance
      myometrial electrical activity?
AB  - OBJECTIVE: To determine whether artificial rupture of membranes (AROM) during
      active phase of labor augments uterine contractility using Electrical Uterine
      Myography (EUM). STUDY DESIGN: A prospective study of 31 women with term
      singleton pregnancy during active phase of labor. Using a non-invasive EUM
      technique, electrical uterine activity was recorded in the 30 min preceding AROM
      and in the immediate 30 min thereafter. Augmentation was defined as >5% increase
      in EUM index between the basal and post-AROM states, representing the mean EUM
      increase of the entire cohort. Low basal uterine contraction was defined as EUM
      index of less than the entire cohort median result prior AROM (3.5 micro-Watt
      Second (mWS)). RESULTS: Mean dilatation in which AROM was preformed was 5.5 +/-
      1.8 cm. There was a significant increase in mean EUM measurement in the post-AROM
      compared to the basal state (3.59 +/- 0.39 versus 3.42 +/- 0.47 mWS, p < 0.001).
      In multivariate analysis, low BMI and low basal uterine contractions were the
      only significant predictors for augmentation following AROM (OR 0.69, 95% C.I
      0.45-0.97, p = 0.009 and OR 16.03, 95% CI 1.90-134.69, p = 0.003, respectively).
      CONCLUSION: Myometrial electrical activity was significantly enhanced following
      AROM. Augmentation was mostly pronounced in patients with lower BMI and initial
      lower basal uterine contraction.

PMID- 24863636
TI  - Structure of the effector-binding domain of deoxyribonucleoside regulator DeoR
      from Bacillus subtilis.
AB  - Deoxyribonucleoside regulator (DeoR) from Bacillus subtilis negatively regulates
      expression of enzymes involved in the catabolism of deoxyribonucleosides and
      deoxyribose. The DeoR protein is homologous to the sorbitol operon regulator
      family of metabolic regulators and comprises an N-terminal DNA-binding domain and
      a C-terminal effector-binding domain. We have determined the crystal structure of
      the effector-binding domain of DeoR (C-DeoR) in free form and in covalent complex
      with its effector deoxyribose-5-phosphate (dR5P). This is the first case of a
      covalently attached effector molecule captured in the structure of a bacterial
      transcriptional regulator. The dR5P molecule is attached through a Schiff base
      linkage to residue Lys141. The crucial role of Lys141 in effector binding was
      confirmed by mutational analysis and mass spectrometry of Schiff base adducts
      formed in solution. Structural analyses of the free and effector-bound C-DeoR
      structures provided a structural explanation for the mechanism of DeoR function
      as a molecular switch. DATABASES: Atomic coordinates and structure factors for
      crystal structures of free C-DeoR and the covalent Schiff base complex of C-DeoR
      with dR5P have been deposited in the Protein Data Bank with accession codes 4OQQ
      and 4OQP, respectively. STRUCTURED DIGITAL ABSTRACT: C-DeoR and C-DeoR bind by x
      ray crystallography (View interaction) DeoR and DeoR bind by molecular sieving
      (1, 2).

PMID- 24863635
TI  - Look inside Look AHEAD: why the glass is more than half-full.
AB  - Look AHEAD is the only long-term study in a large cohort of subjects with type 2
      diabetes that assessed the effect of intensive lifestyle, predominantly diet and
      exercise, on a number of outcomes. While Look AHEAD was not able to detect a
      significant effect of intensive lifestyle modification on cardiovascular
      outcomes, it clearly demonstrated numerous beneficial and sustained effects on
      health outcomes that are relevant to this population. Without the exceptional
      retention of study participants, it would have been difficult to detect these
      benefits. Our review provides a perspective on aspects related to exercise, diet,
      and weight loss in relation to cardiovascular outcomes and potential future
      research. 

PMID- 24863637
TI  - Screening for hepatitis B virus infection in nonpregnant adolescents and adults:
      U.S. Preventive Services Task Force recommendation statement.
AB  - DESCRIPTION: Update of the 2004 U.S. Preventive Services Task Force (USPSTF)
      recommendation on screening for hepatitis B virus (HBV) infection. METHODS: The
      USPSTF reviewed the evidence on the benefits and harms of antiviral treatment,
      the benefits of education or behavior change counseling, and the association
      between improvements in intermediate and clinical outcomes after antiviral
      therapy. POPULATION: This recommendation applies to asymptomatic, nonpregnant
      adolescents and adults at high risk for HBV infection (including those at high
      risk who were vaccinated before being screened for HBV infection).
      RECOMMENDATION: The USPSTF concludes that persons at high risk for infection
      should be screened for HBV infection. (B recommendation).

PMID- 24863638
TI  - Four-membered heterometallacyclic d0 and d1 complexes of Group 4 metallocenes
      with amidato ligands.
AB  - A study of the coordination chemistry of different amidato ligands [(R)N-C(Ph)O]
      (R=Ph, 2,6-diisopropylphenyl (Dipp)) at Group 4 metallocenes is presented. The
      heterometallacyclic complexes [Cp2M(Cl){kappa(2)-N,O-(R)N-C(Ph)O}] M=Zr, R=Dipp
      (1 a), Ph (1 b); M=Hf, R=Ph (2)) were synthesized by reaction of [Cp2MCl2] with
      the corresponding deprotonated amides. Complex 1 a was also prepared by direct
      deprotonation of the amide with Schwartz reagent [Cp2Zr(H)Cl]. Salt metathesis
      reaction of [Cp2Zr(H)Cl] with deprotonated amide [(Dipp)N-C(Ph)O] gave the
      zirconocene hydrido complex [Cp2M(H){kappa(2)-N,O-(Dipp)N-C(Ph)O}] (3). Reaction
      of 1 a with Mg did not result in the desired Zr(III) complex but in formation of
      Mg complex [(py)3Mg(Cl) {kappa(2)-N,O-(Dipp)N-C(Ph)O}] (4; py=pyridine). The
      paramagnetic complexes [Cp'2Ti{kappa(2)-N,O-(R)N-C(Ph)O}] (Cp'=Cp, R=Ph (7 a);
      Cp'=Cp, R=Dipp (7 b); Cp'=Cp*, R=Ph (8)) were prepared by the reaction of the
      known titanocene alkyne complexes [Cp2'Ti(eta(2)-Me3SiC2SiMe3)] (Cp'=Cp (5),
      Cp'=Cp* (6)) with the corresponding amides. Complexes 1 a, 2, 3, 4, 7 a, 7 b, and
      8 were characterized by X-ray crystallography. The structure and bonding of
      complexes 7 a and 8 were also characterized by EPR spectroscopy.

PMID- 24863639
TI  - A cohort study of MFN2 mutations and phenotypic spectrums in Charcot-Marie-Tooth
      disease 2A patients.
AB  - Charcot-Marie-Tooth disease 2A (CMT2A) is the most common axonal form of
      peripheral neuropathy caused by a defect in the mitofusin 2 (MFN2) gene, which
      encodes an outer mitochondrial membrane GTPase. MFN2 mutations result in a large
      range of phenotypes. This study analyzed the prevalence of MFN2 mutation in
      Korean families with their assorted phenotypes (607 CMT families and 160 CMT2
      families). Direct sequencing of the MFN2 coding exons or whole-exome sequencing
      has been applied to identify causative mutations. A total of 21 mutations were
      found in 36 CMT2 families. Comparative genotype-phenotype correlations impacting
      severity, onset age, and specific symptoms were assessed. Most mutations were
      seen in the GTPase domain (~86%). A deletion mutation found in the transmembrane
      helices is reported for the first time, as well as five novel mutations at other
      domains. MFN2 mutations made up 5.9% of total CMT families, whereas 22.9% in CMT2
      families, of which 27.8% occurred de novo. Interestingly, patient phenotypes
      ranged from mild to severe even for the same mutation, suggesting other factors
      influenced phenotype and penetrance. This CMT2A cohort study will be useful for
      molecular diagnosis and treatment of axonal neuropathy.

PMID- 24863641
TI  - A novel tool to detect behavioural symptoms in ALS.
AB  - There is need for a valid, sensitive and short instrument capable of detecting
      and quantifying behavioural changes in ALS, which can be utilized in clinical and
      research settings. This study aimed to 1) develop and validate such an
      instrument; 2) verify the most common behavioural symptoms; and 3) investigate
      longitudinal changes over a six-month period. Two hundred and nineteen patients
      were included. The development sample (n = 140) was used to determine the most
      appropriate items to include in the new tool, the Motor Neuron Disease
      Behavioural Instrument (MiND-B) * , via a data-driven approach. An independent
      sample (n = 79) validated the tool. A more comprehensive sample (n = 50, sub
      classified into ALS and ALS plus) was utilized to verify if the MiND-B could
      detect ALS plus patients. Finally, 20 ALS patients completed the MiND-B after a
      six-month period. Apathy, disinhibition and stereotypical behaviour were all
      found to be very common symptoms in ALS occurring in 75%, 66% and 58%,
      respectively, of cases. Notably, the MiND-B could identify ALS plus patients
      without standard cognitive assessments. In conclusion, the MiND-B tool can detect
      patients with ALS plus reliably, by means of questions to the informant. This
      test could enable ALS centres to evaluate non-motor symptoms and adapt management
      and decision-making approaches as necessary. *only available in the online
      version of the journal. Please find this material with the following direct link
      to the article: http://www.informahealthcare.com/(DOI:
      10.3109/21678421.2014.896927).

PMID- 24863642
TI  - Perifosine induced release of contents of trans cell-barrier transport efficient
      liposomes.
AB  - Perifosine (OPP) containing liposomal formulation was previously found to deliver
      almost half of liposome encapsulated content through a tight cellular barrier in
      vitro. In order to understand the role of different liposome components,
      especially perifosine, in transendothelial transport the physical characteristics
      of liposome membranes composed of phosphatidylcholine, and cholesterol, as a main
      lipid constituents, and variable amount of helper lipids: dioleoyl
      phosphatidylethanolamine (DOPE), and alkylphospholipid perifosine. For this
      purpose, electron paramagnetic resonance (EPR) with computer aided EPR spectra
      simulation and fluorescence polarization spectroscopy were used to investigate
      how different membrane components influence membrane characteristics and the
      release of liposome entrapped substances. Beside methylester of palmitic acid
      with nitroxide group at different position on acyl chain usually used for such
      studies, the spin labeled and fluorescent labeled analog of perifosine were
      introduced. OPP increases membrane fluidity of liposomes as well as the release
      of liposome encapsulated content. The release of neutral molecules increases with
      OPP concentration, while the release of charged molecules is about an order of
      magnitude slower. Optimal OPP concentration, for release of charged molecules, is
      about 15 mol%. These results are one step further toward the conclusion that the
      lysolipid-containing liposomes could be promising trans endothelial delivery
      system, since lysolipids, such as OPP, open tight cellular barriers, as was
      published before, and in the same time induce the release of liposome
      encapsulated content at physiological temperature, as shown here. Since many drug
      delivery systems are being developed, which mainly exploit the transcellular
      route of delivery through barrier-forming cells, we hope that the uniqueness of
      lysolipid-containing liposomes, exploiting the paracellular route, and thus
      avoiding efflux transporters, will foster further research in formulating other
      lysolipid-containing liposomes as drug delivery systems.

PMID- 24863640
TI  - Epidemiology of amyotrophic lateral sclerosis in Emilia Romagna Region (Italy): A
      population based study.
AB  - Our objective was to describe incidence and clinical features of ALS from a
      prospective population-based study in Emilia Romagna Region (ERR). From 2009
      onwards, a prospective registry recorded all incident cases of ALS among
      residents in the ERR (population, 4.4 million inhabitants), involving 17
      neurological departments. For each patient, detailed demographic and clinical
      information was collected by caring physicians. Results showed that from 1
      January 2009 to 31 December 2011, 347 patients received a new diagnosis of ALS
      with a crude incidence rate of 2.63/100,000/year. There was micro-geographic
      heterogeneity throughout ERR, with higher incidence rates in the low density
      population (3.27/100,000) (p < 0.01). ALS patients have been more frequently
      employed in agriculture than the general ERR population (8.64% vs. 4.6%, p <
      0.01). Clinical features were similar to those described in previous population
      based studies. In conclusion, we report incidence rates similar to those reported
      by European registries, reflecting good accuracy of our prospective study. We
      confirmed previous studies reporting higher incidence rates in rural areas and
      among agricultural workers. Although genetics has been gaining increasing
      importance in ALS aetiology, some epidemiological data are still unexplained.
      Identifying geographical areas or populations with high incidence rates can be a
      starting point for identifying environmental risk factors. Further studies having
      this specific aim can shed light on these topics.

PMID- 24863643
TI  - Molecular dynamics simulations of pore formation in stretched
      phospholipid/cholesterol bilayers.
AB  - Molecular dynamics (MD) simulations of pore formation in stretched
      dipalmitoylphosphatidylcholine (DPPC) bilayers containing different
      concentrations of cholesterol (0, 20, 40, and 60 mol%) are presented. The
      stretched bilayers were simulated by constant NPZA||T MD simulations with various
      constant areas. The effects of the cholesterol concentration on pore formation
      are examined in terms of the critical areal strain where the pore is formed, the
      processes of pore formation, and the change in molecular orientation of the DPPC
      molecules by analyzing the order parameters and radial distribution functions of
      the DPPC molecules. With increasing cholesterol concentration, the critical areal
      strain initially increases, peaks at 40 mol%, and then decreases, which agrees
      well with the available experimental data. For the bilayers containing
      cholesterol, DPPC molecules become disordered at low areal strains, whereas the
      order slightly increases when the areal strain exceeds a certain value depending
      on the cholesterol concentration. For 40 mol% cholesterol, the two monolayers in
      the bilayer interpenetrate under high areal strains, inducing an increase of the
      order parameters and the peak positions of the radial distribution function
      compared with their states at low areal strains, indicating the formation of an
      interdigitated gel-phase-like structure. The transient increasing of the order of
      the molecular orientations may inhibit water penetration into the bilayer,
      resulting in increased critical areal strain in the phospholipid/cholesterol
      bilayers.

PMID- 24863644
TI  - Junior Faculty Should Write Review Articles.

PMID- 24863645
TI  - Endometriosis is not associated with inferior pregnancy rates in in vitro
      fertilization: an analysis of 616 patients.
AB  - BACKGROUND/AIMS: To analyze whether the presence of endometriosis per se is
      associated with inferior pregnancy rates in women undergoing in vitro
      fertilization (IVF). METHODS: Between July 2005 and November 2012, a total of 485
      patients with endometriosis under the age of 38 years undergoing their first IVF
      attempt at our center were included; 72 patients had minimal-mild disease and the
      remaining 413 patients had moderate-severe disease. 131 patients with
      laparoscopically confirmed tubal factor infertility not harboring endometriosis
      and hydrosalpinx under the age of 38 years undergoing their first IVF attempt at
      our center served as the control group. RESULTS: The bilateral antral follicle
      count and controlled ovarian hyperstimulation response were diminished in the
      moderate-severe group. However, the implantation, clinical pregnancy, miscarriage
      and live birth rates were comparable among the three groups. The recurrence of
      endometrioma following pre-IVF cystectomy was not associated with inferior
      pregnancy rates. Female age, bilateral antral follicle count and number of
      embryos transferred were noted to be significant independent predictors of live
      birth. CONCLUSION: We conclude that neither the presence nor the extent of
      endometriosis have any detrimental effect on IVF pregnancy rates.

PMID- 24863646
TI  - Oral health workforce planning part 2: figures, determinants and trends in a
      sample of World Dental Federation member countries.
AB  - BACKGROUND AND AIM: A range of factors needs to be taken into account for an
      ideal oral health workforce plan. The figures related to dentists, specialists,
      auxiliaries, practice patterns, undergraduate and continuing dental education,
      laws/regulations, the attitudes of oral health-care providers and the general
      trends affecting the practice patterns, work conditions and preferences of oral
      health-care providers are among such determinants. Thus, the aim of the present
      study was to gather such information from a sample of World Dental Federation
      (FDI) member countries with different characteristics. METHODS: A cross-sectional
      survey study was carried out among a sample of FDI member countries between March
      2, 2012 and March 27, 2012. A questionnaire was developed addressing some main
      determinants of oral health workforce, such as its structure, involvement of the
      public/private sector to provide oral health-care services, specialty services,
      dental schools, trends in workforce and compliance with oral health needs, and a
      descriptive analysis was performed. The countries were classified as developed
      and developing countries and Mann-Whitney U-tests and chi-square tests were used
      to identify potential significant differences (P > 0.05) between developed and
      developing countries. All data were processed in SPSS v.19. RESULTS: In the18
      questionnaires processed, the median number of dentists (P = 0.005), dental
      practices (P = 0.002), hygienists (P = 0.005), technicians (P = 0.013) and
      graduates per year (P = 0.037) was higher in developed countries. Only 12.5% of
      developed and 22.2% of developing countries reported having optimal number of
      graduates per year. It was noted that 66.7% of developing countries had more
      regions lacking enough dentists to meet the demand (P = 0.050) and 77.8% lacked
      the necessary specialist care (P = 0.015). Although developing countries reported
      mostly an oversupply of dentists, regardless of the level of development most
      countries did not report an oversupply of specialists. Most developed countries
      did not feel that their regulations (87.5%) complied with the needs and demands
      of the population and most developing countries did not feel that their
      undergraduate dental education (62.5%) complied. Migrating to other countries was
      a trend seen in developing countries, while, despite increased numbers of
      dentists, underserved areas and communities were reported. DISCUSSION: The cross
      sectional survey study suggests that figures related to optimum or ideal oral
      health workforce and fair distribution of the available workforce does not seem
      to be achieved in many parts of the world. Further attention also needs to be
      dedicated to general trends that have the capacity to affect future oral health
      workforce.

PMID- 24863647
TI  - Antisperm antibodies: invaluable tools toward the identification of sperm
      proteins involved in fertilization.
AB  - The identification of sperm proteins involved in fertilization has been the
      subject of numerous investigations. Much interest has been dedicated to naturally
      occurring antisperm antibodies (ASA) and their impact in fertility. Their
      presence in men and women has been associated with 2-50% of infertility cases.
      ASA may impair pre- and post-fertilization steps. Experimental models have been
      developed using sperm proteins as immunogens to evaluate their involvement in
      sperm function. Our team has pursued investigations to assess ASA presence in
      biological fluids from patients consulting for infertility and their effect on
      fertilization. We found ASA in follicular fluids with ability of inducing the
      acrosome reaction and blocking sperm-zona pellucida interaction and used them to
      identify sperm entities involved in these events. We generated and utilized
      antibodies against proacrosin/acrosin to characterize the sperm protease system.
      We implemented an ELISA to detect proacrosin/acrosin antibodies in human sera and
      evaluated their impact upon fertility by developing in vitro assays and a gene
      immunization model. This review presents a summary of ASA history, etiology,
      current approaches for detection and effects upon fertility. ASA (naturally
      occurring, generated by animal immunization and/or of commercial origin) are
      invaluable tools to understand the molecular basis of fertilization, better
      diagnose/treat immunoinfertility and develop immunocontraceptive methods. 

PMID- 24863648
TI  - Downregulation of survivin by siRNA inhibits invasion and promotes apoptosis in
      neuroblastoma SH-SY5Y cells.
AB  - Neuroblastoma is a solid tumor that occurs mainly in children. Malignant
      neuroblastomas have a poor prognosis because conventional chemotherapeutic agents
      are not very effective. Survivin, a member of the inhibitor of the apoptosis
      protein family, plays a significant role in cell division, inhibition of
      apoptosis, and promotion of cell proliferation and invasion. Previous studies
      found that survivin is highly expressed in some malignant neuroblastomas and is
      correlated with poor prognosis. The aim of this study was to investigate whether
      survivin could serve as a potential therapeutic target of human neuroblastoma. We
      employed RNA interference to reduce survivin expression in the human
      neuroblastoma SH-SY5Y cell line and analyzed the effect of RNA interference on
      cell proliferation and invasion in vitro and in vivo. RNA interference of
      survivin led to a significant decrease in invasiveness and proliferation and
      increased apoptosis in SH-SY5Y cells in vitro. RNA interference of survivin
      inhibited tumor growth in vivo by 68 +/- 13% (P=0.002) and increased the number
      of apoptotic cells by 9.8 +/- 1.2% (P=0.001) compared with negative small
      interfering RNA (siRNA) treatment controls. Moreover, RNA interference of
      survivin inhibited the formation of lung metastases by 92% (P=0.002) and reduced
      microvascular density by 60% (P=0.0003). Survivin siRNA resulted in significant
      downregulation of survivin mRNA and protein expression both in vitro and in vivo
      compared with negative siRNA treatment controls. RNA interference of survivin was
      found to be a potent inhibitor of SH-SY5Y tumor growth and metastasis formation.
      These results support further clinical development of RNA interference of
      survivin as a treatment of neuroblastoma and other cancer types.

PMID- 24863649
TI  - Evaluation of cardiovascular toxicity of carbon nanotubes functionalized with
      sodium hyaluronate in oral regenerative medicine.
AB  - It has been demonstrated that carbon nanotubes (CNTs) associated with sodium
      hyaluronate (HY-CNTs) accelerate bone repair in the tooth sockets of rats. Before
      clinical application of HY-CNTs, it is important to assess their
      biocompatibility. Moreover, cardiac toxicity may be caused by the translocation
      of these particles to the blood stream. The aim of this study was to evaluate
      possible changes in cardiovascular function in male Wistar rats whose tooth
      sockets were treated with either CNTs or HY-CNTs (100 MUg/mL, 0.1 mL). Blood
      pressure and heart rate were monitored in conscious rats 7 days after treatment.
      Cardiac function was evaluated using the Langendorff perfusion technique. The
      data showed no changes in blood pressure or heart rate in rats treated with
      either CNTs or HY-CNTs, and no significant changes in cardiac function were found
      in any of the groups. To confirm these findings, experiments were conducted in
      rats injected intraperitoneally with a high concentration of either CNTs or HY
      CNTs (0.75 mg/kg). The same parameters were analyzed and similar results were
      observed. The results obtained 7 days following injection indicate that the
      administration of low concentrations of CNTs or HY-CNTs directly into tooth
      sockets did not cause any significant change in cardiovascular function in the
      rats. The present findings support the possibility of using these biocomposites
      in humans.

PMID- 24863651
TI  - PIN-driven polar auxin transport in plant developmental plasticity: a key target
      for environmental and endogenous signals.
AB  - Plants master the art of coping with environmental challenges in two ways: on the
      one hand, through their extensive defense systems, and on the other, by their
      developmental plasticity. The plant hormone auxin plays an important role in a
      plant's adaptations to its surroundings, as it specifies organ orientation and
      positioning by regulating cell growth and division in response to internal and
      external signals. Important in auxin action is the family of PIN-FORMED (PIN)
      auxin transport proteins that generate auxin maxima and minima by driving polar
      cell-to-cell transport of auxin through their asymmetric subcellular
      distribution. Here, we review how regulatory proteins, the cytoskeleton, and
      membrane trafficking affect PIN expression and localization. Transcriptional
      regulation of PIN genes alters protein abundance, provides tissue-specific
      expression, and enables feedback based on auxin concentrations and crosstalk with
      other hormones. Post-transcriptional modification, for example by PIN
      phosphorylation or ubiquitination, provides regulation through protein
      trafficking and degradation, changing the direction and quantity of the auxin
      flow. Several plant hormones affect PIN abundance, resulting in another means of
      crosstalk between auxin and these hormones. In conclusion, PIN proteins are
      instrumental in directing plant developmental responses to environmental and
      endogenous signals.

PMID- 24863650
TI  - Attentional bias modulation by reappraisal in patients with generalized anxiety
      disorder: an event-related potential study.
AB  - Affective states influence subsequent attention allocation. We evaluated
      emotional negativity bias modulation by reappraisal in patients with generalized
      anxiety disorder (GAD) relative to normal controls. Event-related potential (ERP)
      recordings were obtained, and changes in P200 and P300 amplitudes in response to
      negative or neutral words were noted after decreasing negative emotion or
      establishing a neutral condition. We found that in GAD patients only, the mean
      P200 amplitude after negative word presentation was much higher than after the
      presentation of neutral words. In normal controls, after downregulation of
      negative emotion, the mean P300 amplitude in response to negative words was much
      lower than after neutral words, and this was significant in both the left and
      right regions. In GAD patients, the negative bias remained prominent and was not
      affected by reappraisal at the early stage. Reappraisal was observed to have a
      lateralized effect at the late stage.

PMID- 24863652
TI  - Hyaluronic acid production with Corynebacterium glutamicum: effect of media
      composition on yield and molecular weight.
AB  - AIMS: Corynebacterium glutamicum was tested as an alternative host for
      heterologous production of hyaluronic acid (HA). METHODS AND RESULTS: A set of
      expression vectors containing hasA, encoding HA synthase from Streptococcus equi
      subsp. zooepidemicus, alone or in combination with genes encoding enzymes for HA
      precursor production (hasB, hasC, glmU from Pseudomonas putida KT2440) or
      bacterial haemoglobin (vgb from Vitreoscilla sp.) was constructed. Recombinant
      Coryne. glutamicum strains were cultivated in two different minimal media, CGXII
      and MEK700. HA was isolated from the culture broth by ethanol precipitation or
      ultrafiltration. Analyses of the isolated HA revealed that overall production was
      higher in CGXII medium (1241 mg l(-1)) than in MEK700 medium (363 mg l(-1)), but
      molecular weight of the product was higher in MEK700 (>1.4 MDa) than in CGXII
      (<270 kDa). Coexpression of hasB, hasC or glmU had no effect on HA yield and did
      not improve molecular weight of the product. Coexpression of vgb lowered HA yield
      about 1.5-fold and did not affect molecular weight of the product. Microscopy of
      negative-stained cultures revealed that Coryne. glutamicum produces no distinct
      HA capsule. CONCLUSIONS: Regulation of cell growth and gene expression level of
      hasA are reasonable starting points for controlling the molecular weight of HA
      produced by Coryne. glutamicum. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Corynebacterium glutamicum has a great potential as an alternative production
      host for HA. The fact that Coryne. glutamicum produces no distinct HA capsule
      facilitates HA isolation and improves overall yield.

PMID- 24863653
TI  - The VF rat with abnormal myelinogenesis has a mutation in Dopey1.
AB  - The vacuole formation (VF) rat is an autosomal recessive myelin mutant
      characterized by generalized tremor, hypomyelination, and periaxonal vacuole
      formation of the central nervous system (CNS). Here, we report the most likely
      causative gene for neurological disease in the VF rat and pursue its roles in the
      development and maintenance of the CNS myelin. We identified a nonsense mutation
      in the dopey family member 1 (Dopey1) located on rat chromosome 8. Expression
      level of Dopey1 mRNA was decreased and DOPEY1 protein was undetectable both in
      the white and gray matter of the spinal cords in the VF rats. Double
      immunohistochemistry demonstrated that DOPEY1 was mainly expressed in neurons and
      oligodendrocytes in the wild-type rats, whereas no positive cells were detected
      in the VF rats. We also demonstrated a marked reduction in myelin components both
      at mRNA and protein levels during myelinogenesis in the VF rats. In addition,
      proteolipid protein and myelin-associated glycoprotein accumulated in
      oligodendrocyte cell body, suggesting that Dopey1 is likely to be involved in the
      traffic of myelin components. Our results highlighted the importance of Dopey1
      for the development and maintenance of the CNS myelin.

PMID- 24863654
TI  - Real time PCR quantification of viable Mycobacterium tuberculosis from sputum
      samples treated with propidium monoazide.
AB  - Diagnostic methods of TB, nowadays, are prone to delay in diagnosis, increased
      false negative results and are not sensitive to many forms of paucibacillary
      disease. The aims of this study were to implement a quantitative nucleic acid
      based diagnostic test for paucibacillary tuberculosis, enabling the
      identification and quantification of viable Mycobacterium tuberculosis bacilli by
      quantitative Real-Time PCR (qRT-PCR). The intergenic region of the single-copy
      inhA-mabA gene was chosen as the target region for design of primers and probes
      conjugated with fluorophores. The construction of synthetic DNA flanking the
      target region served as standards for absolute quantification of nucleic acids.
      Using the intercaling dye, propidium monoazide, we were able to discriminate
      between viable and dead cells of M. tuberculosis. The diagnosis method showed a
      broad sensitivity (96.1%) when only compared to samples of smear-positive sputum
      and ROC analyses shows that our approach performed well and yielded a specificity
      of 84.6% and a sensitivity of 84.6% when compared to M. tuberculosis colony
      forming units counting. 

PMID- 24863655
TI  - The PD-associated alpha-synuclein promoter Rep1 allele 2 shows diminished
      frequency in restless legs syndrome.
AB  - Gain-of-function mutations of alpha-synuclein (SNCA) are known to trigger
      Parkinson's disease (PD) with striatal dopaminergic deficits and a reduction of
      spontaneous movements. The longest size variant (allele 2) of the complex
      microsatellite repeat Rep1 within the SNCA gene promoter is known to confer a PD
      risk. We now observed this Rep1 allele 2 to show significantly decreased
      frequency in restless legs syndrome (RLS) in a genotyping study of 258 patients
      versus 235 healthy controls from Germany. Given that RLS is a disease with
      increased spontaneous movements and with increased striatal dopamine signaling,
      these novel data appear plausible. The scarcity of this alpha-synuclein gain-of
      function variant in RLS might suggest that a low alpha-synuclein function via the
      SNARE complex in presynaptic vesicle release and neurotransmission of the
      striatum contributes to RLS pathogenesis.

PMID- 24863656
TI  - Transforming growth factor-beta-induced lncRNA-Smad7 inhibits apoptosis of mouse
      breast cancer JygMC(A) cells.
AB  - Transforming growth factor (TGF)-beta exhibits both pro-apoptotic and anti
      apoptotic effects on epithelial cells in a context-dependent manner. The anti
      apoptotic function of TGF-beta is mediated by several downstream regulatory
      mechanisms, and has been implicated in the tumor-progressive phenotype of breast
      cancer cells. We conducted RNA sequencing of mouse mammary gland epithelial
      (NMuMG) cells and identified a long non-coding RNA, termed lncRNA-Smad7, which
      has anti-apoptotic functions, as a target of TGF-beta. lncRNA-Smad7 was located
      adjacent to the mouse Smad7 gene, and its expression was induced by TGF-beta in
      all of the mouse mammary gland epithelial cell lines and breast cancer cell lines
      that we evaluated. Suppression of lncRNA-Smad7 expression cancelled the anti
      apoptotic function of TGF-beta. In contrast, forced expression of lncRNA-Smad7
      rescued apoptosis induced by a TGF-beta type I receptor kinase inhibitor in the
      mouse breast cancer cell line JygMC(A). The anti-apoptotic effect of lncRNA-Smad7
      appeared to occur independently of the transcriptional regulation by TGF-beta of
      anti-apoptotic DEC1 and pro-apoptotic Bim proteins. Small interfering RNA for
      lncRNA-Smad7 did not alter the process of TGF-beta-induced epithelial-mesenchymal
      transition, phosphorylation of Smad2 or expression of the Smad7 gene, suggesting
      that the contribution of this lncRNA to TGF-beta functions may be restricted to
      apoptosis. Our findings suggest a complex mechanism for regulating the anti
      apoptotic and tumor-progressive aspects of TGF-beta signaling. 

PMID- 24863657
TI  - Control of microorganisms of oral health interest with Arctium lappa L. (burdock)
      extract non-cytotoxic to cell culture of macrophages (RAW 264.7).
AB  - OBJECTIVES: To evaluate the antimicrobial activity of Arctium lappa L. extract on
      Staphylococcus aureus, S. epidermidis, Streptococcus mutans, Candida albicans, C.
      tropicalis and C. glabrata. In addition, the cytotoxicity of this extract was
      analyzed on macrophages (RAW 264.7). DESIGN: By broth microdilution method,
      different concentrations of the extract (250-0.4 mg/mL) were used in order to
      determine the minimum microbicidal concentration (MMC) in planktonic cultures and
      the most effective concentration was used on biofilms on discs made of acrylic
      resin. The cytotoxicity A. lappa L. extract MMC was evaluated on RAW 264.7 by MTT
      assay and the quantification of IL-1beta and TNF-alpha by ELISA. RESULTS: The
      most effective concentration was 250 mg/mL and also promoted significant
      reduction (log10) in the biofilms of S. aureus (0.438 +/- 0.269), S. epidermidis
      (0.377 +/- 0.298), S. mutans (0.244 +/- 0.161) and C. albicans (0.746 +/- 0.209).
      Cell viability was similar to 100%. The production of IL-1beta was similar to the
      control group (p>0.05) and there was inhibition of TNF-alpha (p<0.01).
      CONCLUSIONS: A. lappa L. extract was microbicidal for all the evaluated strains
      in planktonic cultures, microbiostatic for biofilms and not cytotoxic to the
      macrophages.

PMID- 24863658
TI  - Chemopreventive activity of apple extract following medium-term oral
      carcinogenesis assay induced by 4-nitroquinoline-1-oxide.
AB  - OBJECTIVE: The aim of this study was to evaluate the chemopreventive activity of
      an apple extract following medium-term oral carcinogenesis assay induced by 4
      nitroquinoline-1-oxide (4NQO). METHODS: A total of 30 male Wistar rats were
      distributed into five groups as follows (n=6 per group): Group 1, negative
      control group (non-treated group); Group 2, received 4NQO during 8 weeks in
      drinking water and treated with apple extract at 1% by gavage between the first
      and fourth weeks daily (initiation phase); Group 3, received 4NQO for 8 weeks in
      drinking water and treated with apple extract by gavage at 1% between the fifth
      and eighth weeks daily (promotion phase); Group 4, received apple extract at 1%
      by gavage for 8 consecutive weeks only; and Group 5, received 4NQO for 8 weeks in
      drinking water daily. RESULTS: Histopathological analysis revealed decreased
      hyperplasic lesions in Group 2 when compared with Group 5. Likewise, decreased
      dysplastic lesions in Group 3 were observed when compared with Group 5. In Groups
      2 and 3, decreased COX-2 and TNF-alpha gene expressions were observed when
      compared with Group 5. Cytochrome c and caspase 3 levels increased in Groups 2
      and 3 when compared with Group 5. CONCLUSION: In conclusion, our results
      demonstrate that apple extract suppresses rat tongue carcinogenesis as a result
      of anti-inflammatory activity and apoptosis through the intrinsic mitochondrial
      pathway.

PMID- 24863659
TI  - Periodontal disease and high doses of inhaled corticosteroids alter NTPDase
      activity in the blood serum of rats.
AB  - BACKGROUND: Certain drugs such as glucocorticoids may interfere with the
      modulation of periodontal disease. In contrast, corticosteroid treatment has been
      associated with a protective effect with regard to periodontal breakdown,
      depending on the dose, pathway, and exposure time. Considering the potential
      relevance of nucleotidases in coordinating the cardiovascular system and
      inflammation processes, the aim of this study was to investigate the nucleotidase
      activities in the blood serum of rats with periodontal disease exposed
      chronically to inhaled corticosteroids. METHODS: Adult male Wistar rats (n=26)
      were randomly assigned to one of the following four study groups: a control group
      that received no intervention; a periodontal disease group that received saline
      solution; a 'low dose' group that received 30 MUg of budesonide daily; and a
      corresponding 'high dose' group that received 100 MUg daily over a 15-day time
      course. The hydrolysis of ATP, ADP, and AMP were analysed in blood serum.
      RESULTS: Periodontal disease diminished the hydrolysis of ATP and enhanced the
      hydrolysis of ADP. Repeated administration of either a low or high dose in the
      periodontal disease model of inhaled corticosteroids reversed the observed
      increase in ADP hydrolysis, and only the repeated administration of low doses of
      inhaled corticosteroids was able to reverse the decrease in the hydrolysis of ATP
      induced by periodontal disease. CONCLUSION: The variables investigated in this
      study may be involved in the pathophysiology of periodontal disease and may
      participate in the mechanisms that mediate the development of some of the side
      effects of inhaled corticosteroids.

PMID- 24863660
TI  - [Current therapeutic strategies in lysosomal disorders].
AB  - The lysosomal storage disorders (LSD) comprise a heterogeneous group of inborn
      errors of metabolism. The resulting enzymatic defect leads to accumulation of its
      substrate in the lysosome. Their clinical patterns reflect the site of substrate
      storage. Central nervous system involvement is often present in the younger
      patients affected by the most severe phenotypes. Substantial progress has been
      made in the pathophysiological knowledge, leading to new therapeutic options in
      LSD. Enzyme replacement therapy (ERT) is the dominant approach and is actually
      proposed in six LSD: Gaucher disease, Fabry disease, Pompe disease and
      mucopolysaccharidoisis (MPS) I (Hurler disease), II (Hunter disease) and VI
      (Maroteaux-Lamy disease). This treatment reduces lysosomal storage, and sometimes
      reduces, but most often limits the progression of visceral involvement and of its
      clinical consequences. However, ERT does not cross the blood-brain barrier and is
      ineffective on neurological symptoms. In the younger patients with MPS I (Hurler
      disease) and with selected cases of other LSD, haematopoietic stem cell
      transplantation remains the optimal option. Other strategies using small
      molecules are being explored in order to cross the blood-brain barrier. This
      includes substrate reduction or depletion therapies, which decrease the amount of
      substrate, and the use of pharmacological chaperones, which enhance the residual
      activity of the mutant enzyme. Miglustat is the proposed substrate reduction
      therapy in Niemann-Pick C disease and clinical trials are actually performed in
      several LSD using other substrate reduction or chaperone drugs. 

PMID- 24863661
TI  - [Vaccination and pregnancy].
AB  - Vaccination against influenza is recommended during the vaccination period in
      pregnant women regardless of trimester. In contrast, administration of live
      vaccines, such as the vaccine against varicella, MMR (measles-mumps-rubella) is
      contraindicated in pregnant women. Vaccinations against hepatitis B, diphtheria,
      tetanus, poliomyelitis, hepatitis A can be made as indicated. Vaccination against
      yellow fever may be considered in pregnant women travelling to endemic countries.
      In post-partum period, live vaccines may be administered if necessary, especially
      vaccination against whooping cough for women not to date with their vaccinations.
      Vaccination against yellow fever is contraindicated in case of breast feeding.
      Prevention of pertussis in newborns is based in France on vaccination of the
      mothers in the post-partum period, and the close contacts of the newborn during
      the pregnancy ("cocooning"). 

PMID- 24863662
TI  - [Home blood pressure measurement and pregnancy].
AB  - Hypertension during pregnancy is associated with high perinatal morbidity and
      mortality The prevalence of white coat hypertension is high during pregnancy and
      is associated with a good prognosis. This must be excluded before beginning
      antihypertensive treatment. When to use HBPM during pregnancy? To confirm the
      diagnosis of hypertension; to monitor BP during pregnancy and to alert the
      obstetrician when severe hypertension occurs; to manage BP treatment and avoid
      excessive treatment. How to use HBPM during pregnancy? To get an adapted and
      validated BP device during pregnancy; to compare the results with reference HBP
      values during the 3 trimesters of pregnancy. Telemetry to monitor BP at home
      during pregnancy is a feasible, safe and well-tolerated alternative to repeated
      clinic visits or BP monitoring during hospitalisations. 

PMID- 24863663
TI  - [Varicella-zoster virus and pregnancy].
AB  - The incidence of varicella is low in pregnant women, and estimated around 1/1000
      pregnancies. Vaccination is the cornerstone of prevention, but is contraindicated
      during pregnancy. Varicella is more severe in pregnant women. The risk of viral
      pneumonia is not increased, but VZV-associated pneumonia is usually more severe
      in pregnant women. Infection between 0-20 WG is associated with a 2 % risk of
      congenital varicella syndrome. Infection between D-5 and D+2 of delivery is
      associated with high risk of severe neonatal infection. Non-immune pregnant women
      with significant exposure to VZV require post-exposure prophylaxis with specific
      anti-VZV immunoglobulins that should be administered ideally within 4 days post
      exposure and maximum within 10 days of exposure. Anti-VZV immunoglobulins are
      available in France in the context of an approved expanded access to an
      investigational new drug. Pregnant women with varicella should receive within 24
      hours antiviral treatment based either on valaciclovir or, in case of severe
      infection, intravenous aciclovir. Both drugs were shown safe during pregnancy,
      even during the first trimester. Neonates born from mothers who developed
      varicella between D-5 and D+2 of delivery should also receive as soon as possible
      specific anti-VZV immunoglobulins.

PMID- 24863664
TI  - [Retroperitoneal fibrosis].

PMID- 24863665
TI  - The effects of aging on changes in regional cerebral blood flow in schizophrenia.
AB  - AIMS: Although there have been no conclusive pathophysiological findings in
      support of the degeneration theory in the etiology of schizophrenia to date,
      results of our neuroimaging studies suggest functional changes in the brains of
      schizophrenics. We evaluated age-related changes of brain perfusion in medicated
      patients with schizophrenia. METHOD: In this study, we evaluated age-related
      changes in brain perfusion in medicated schizophrenia patients (n = 44) and
      control subjects (n = 37) undergoing (99m)Tc-ethyl cysteinate dimer single-photon
      emission computed tomography. RESULT: Although the regional cerebral blood flow
      (rCBF) was found to be reduced in bilateral frontal lobes by analysis with age in
      the patients with schizophrenia, significant differences compared to controls in
      age effects on perfusion were found in the patients with schizophrenia in
      bilateral temporal lobes. Moreover, in multiple regression analysis including
      age, total time of treatment and overall neuroleptic dose, rCBF was found to be
      reduced in bilateral frontal and parietal lobes. As a result, cerebral perfusion
      in temporal lobes with schizophrenia might be related to age rather than
      medication. CONCLUSION: In this study, the patients with schizophrenia appeared
      to have significant bilateral temporal hypoperfusion related to age compared with
      controls. And bilateral temporal rCBF is decreased in patients with schizophrenia
      and even more in older schizophrenia patients. These changes might be consistent
      with degenerative changes observed in patients with schizophrenia and be a
      promising method for the efficient development of a treatment strategy by
      measuring temporal perfusion in patients with schizophrenia.

PMID- 24863666
TI  - Differential effects of age on large artery stiffness and minimal vascular
      resistance in normotensive and mildly hypertensive individuals.
AB  - Large artery stiffness and small artery structural changes are both
      cardiovascular risk factors. Arterial stiffness increases with age and blood
      pressure (BP), but it is unclear in which way large artery pulse wave velocity
      (PWV) and peripheral vascular resistance are related and whether age has any
      influence. In a cross-sectional study, PWV and forearm minimum vascular
      resistance (Rmin ) was compared with emphasis on the impact of age. Normotensive
      (n = 53) and untreated hypertensive (n = 23) subjects were included based on 24-h
      BP measurements. Age ranged from 21 to 79 years with an even distribution from
      each age decade. PWV was assessed using tonometry. Forearm Rmin was measured by
      venous occlusion plethysmography at maximal vasodilatation induced by 10 min of
      ischaemia in combination with skin heating and hand grip exercise. In both
      normotensive and hypertensive subjects, PWV correlated significantly with age and
      BP. Based on median age, both groups were assigned into two equally large
      subgroups. Normotensive older (66 +/- 7 years) and younger (35 +/- 10 years)
      persons had different carotid-femoral PWV (7.9 +/- 1.8 versus 5.7 +/- 0.9 m/s,
      P<0.01), but similar Rmin values (3.7 +/- 0.9 versus 3.6 +/- 1.2 mmHg/ml/min/100
      ml). Hypertensive older (63 +/- 6 years) and younger (40 +/- 10 years) also had
      different PWV (8.0 +/- 1.5 versus 6.7 +/- 1.1 m/s, P<0.05), but the older had
      lower Rmin (3.1 +/- 0.8 versus 4.7 +/- 2.2 mmHg/ml/min/100 ml, P<0.05). In a
      regression analysis adjusting for age, BP, gender and heart rate, no correlation
      was seen between PWV and Rmin . The data suggest that age differentially affects
      PWV and Rmin and that BP can increase in older persons without affecting Rmin .

PMID- 24863667
TI  - Influence of Alzheimer's disease genes on cognitive decline: the Guangzhou
      Biobank Cohort Study.
AB  - Cognitive decline is a reduction in cognitive ability usually associated with
      aging, and those with more extreme cognitive decline either have or are at risk
      of progressing to mild cognitive impairment and dementia including Alzheimer's
      disease (AD). We hypothesized that genetic variants predisposing to AD should be
      predictive of cognitive decline in elderly individuals. We selected 1325 subjects
      with extreme cognitive decline and 1083 well-matched control subjects from the
      Guangzhou Biobank Cohort Study in which more than 30,000 southern Chinese older
      people have been recruited and followed up. Thirty single-nucleotide
      polymorphisms in 29 AD-associated genes were genotyped. No statistically
      significant allelic associations with cognitive decline were found by individual
      variant analysis. At the level of genotypic association, we confirmed that the
      APOE epsilon4 homozygote significantly accelerated cognitive decline and found
      that carriers of the ACE rs1800764_C allele were more likely to show cognitive
      decline than noncarriers, particularly in those without college education.
      However, these effects do not survive after multiple testing corrections, and
      together they only explain 1.7% of the phenotypic variance in cognitive score
      change. This study suggests that AD risk variants and/or genes are not powerful
      predictors of cognitive decline in our Chinese sample. 

PMID- 24863668
TI  - Iron overload accelerates neuronal amyloid-beta production and cognitive
      impairment in transgenic mice model of Alzheimer's disease.
AB  - Iron dyshomeostasis is proving increasingly likely to be involved in the
      pathology of Alzheimer's disease (AD); yet, its mechanism is not well understood.
      Here, we investigated the AD-related mechanism(s) of iron-sulfate exposure in
      vitro and in vivo, using cultured primary cortical neurons and APP/PS1 AD-model
      mice, respectively. In both systems, we observed iron-induced disruptions of
      amyloid precursor protein (APP) processing, neuronal signaling, and cognitive
      behavior. Iron overload increased production of amyloidogenic KPI-APP and amyloid
      beta. Further, this APP misprocessing was blocked by MK-801 in vitro, suggesting
      the effect was N-methyl-D-aspartate receptor (NMDAR) dependent. Calcium imaging
      confirmed that 24 hours iron exposure led to disrupted synaptic signaling by
      augmenting GluN2B-containing NMDAR expression-GluN2B messenger RNA and protein
      levels were increased and promoting excessing extrasynaptic NMDAR signaling. The
      disrupted GluN2B expression was concurrent with diminished expression of the
      splicing factors, sc35 and hnRNPA1. In APP/PS1 mice, chronic iron treatment led
      to hastened progression of cognitive impairment with the novel object recognition
      discrimination index, revealing a deficit at the age of 4 months, concomitant
      with augmented GluN2B expression. Together, these data suggest iron-induced APP
      misprocessing and hastened cognitive decline occur through inordinate
      extrasynaptic NMDAR activation.

PMID- 24863669
TI  - Combining photoredox-catalyzed trifluoromethylation and oxidation with DMSO:
      facile synthesis of alpha-trifluoromethylated ketones from aromatic alkenes.
AB  - Trifluoromethylated ketones are useful building blocks for organic compounds with
      a trifluoromethyl group. A new and facile synthesis of ketones with a
      trifluoromethyl substituent in the alpha-position proceeds through a one-pot
      photoredox-catalyzed trifluoromethylation-oxidation sequence of aromatic alkenes.
      Dimethyl sulfoxide (DMSO) serves as a key and mild oxidant under these
      photocatalytic conditions. Furthermore, an iridium photocatalyst, fac[Ir(ppy)3 ]
      (ppy=2-phenylpyridine), turned out to be crucial for the present photoredox
      process. 

PMID- 24863670
TI  - Nitric oxide induces apoptosis in human gingival fibroblast through mitochondria
      dependent pathway and JNK activation.
AB  - AIM: To investigate the molecular mechanisms of nitric oxide (NO)-induced
      cytotoxic effect in human gingival fibroblast (HGF) cells. METHODOLOGY: After
      sodium nitroprusside (SNP), as NO donor, was treated to HGF, viability was
      measured by MTT assay and apoptosis was determined by TUNEL and DNA fragmentation
      assay. Mitochondrial membrane potential was detected using confocal microscopy,
      and caspase activity assay was measured by spectrophotometer. Mitogen-activated
      protein kinases (MAPK) activation, Bax/Bcl-2 ratio and cytochrome c release were
      analysed by Western blot analyses. Cells were exposed to MAPK inhibitors (U0126,
      SB203580 and SP600125) before SNP treatment to investigate the effects of MAPK
      kinases on the NO-induced apoptosis in HGF. Statistical analysis was performed
      using one-way analysis of variance with the Student-Newman-Keuls post hoc test
      for multiple group comparison. RESULTS: Apoptosis was significantly increased (P
      = 0.011 and 0.0004, respectively) in the presence of SNP (1 and 3 mmol L(-1) )
      after 12 h in HGF. However, 1H-[1,2,4] oxadiatolo [4, 3-a] cluinoxaline-1-one
      (ODQ), a soluble guanylate cyclase inhibitor, did not block the decrement of cell
      viability by NO. SNP treatment induced the loss of mitochondrial membrane
      potential, release of cytochrome c, increased Bax/Bcl-2 ratio and activation of
      caspases in HGF. Also, SNP treatment increased phosphorylation of MAPKinases and
      c-Jun N-terminal kinase (JNK) inhibitor (5 and 10 MUmol L(-1) ) rescued cell
      viability decreased by SNP in HGF (P = 0.024 and 0.0149, respectively).
      CONCLUSION: Nitric oxide induced apoptosis in human gingival fibroblast through
      the mitochondria-mediated pathway by regulation of Bcl-2 family and JNK
      activation.

PMID- 24863672
TI  - Monocyte count and mean platelet volume may not be related to the pathogenesis of
      coronary vasospasm.

PMID- 24863671
TI  - Age-related changes in visual contour integration: implications for physiology
      from psychophysics.
AB  - Visual contour detection is enhanced by grouping principles, such as proximity
      and collinearity, which appear to rely on horizontal connectivity in visual
      cortex. Previous experiments suggest that children require greater proximity to
      detect contours and that, unlike adults, collinearity does not compensate for
      their proximity limitation. Over two experiments we test whether closure, a
      global property known to facilitate contour detection, compensates for this
      limitation. Adults and children (3-9 years old) performed a 2AFC task; one panel
      contained an illusory contour (closed or open) in visual noise, and one only
      noise. The experiments were identical except proximity was doubled in Exp. 2,
      enabling shorter-range spatial integration. Results suggest children are limited
      by proximity, and that closure did not reliably improve their performance as it
      did for adults. We conclude that perceptual maturity lags behind anatomy within
      this system, and suggest that slow statistical learning of long-range orientation
      correlations controls this disparity.

PMID- 24863674
TI  - Two-dimensional NMR spectroscopy with temperature-sweep.
AB  - Two-dimensional nuclear magnetic resonance (NMR) spectroscopy is useful for
      studying temperature-dependent effects on molecular structure. However,
      experimental time is usually long, because sampling is repeated at several
      temperatures. A novel solution to the problem is proposed, in which signal
      sampling is performed in parallel to the linear temperature-sweep. 

PMID- 24863673
TI  - Effects of acivicin on growth, mycotoxin production and virulence of
      phytopathogenic fungi.
AB  - Acivicin is an inhibitor of gamma-glutamyl transpeptidase and glutamine
      amidotransferase. When grown on a synthetic minimal agar medium, acivicin
      strongly inhibited the growth of Magnaporthe oryzae and Alternaria brassicicola,
      and to a lesser extent, Botrytis cinerea. However, only partial or marginal
      growth inhibition was observed with regard to Fusarium sporotrichioides and
      Fusarium graminearum. The growth retardation caused by acivicin was significantly
      alleviated by cultivating the fungus on a nutrient-rich medium. The inhibition of
      M. oryzae growth caused by 1 MUmol l(-1) of acivicin on minimal agar medium was
      subdued by the addition of specific single amino acids, including His, a branched
      chain amino acid (Leu, Ile or Val), an aromatic amino acid (Trp, Tyr or Phe), Met
      or Gln, at a concentration of 0.4 mmol l(-1). Trichothecene production by F.
      graminearum in trichothecene-inducing liquid medium was reduced significantly in
      the presence of acivicin despite its inability to inhibit growth in the
      trichothecene-inducing liquid medium. Foliar application of conidia in the
      presence of acivicin reduced the severity of rice blast disease caused by M.
      oryzae. These results suggest the usefulness of this modified amino acid natural
      product to mitigate agricultural problems caused by some phytopathogenic fungi.
      Significance and impact of the study: Fusarium head blight or scab disease and
      rice blast, caused by Fusarium graminearum and Magnaporthe oryzae, respectively,
      are major diseases of cereal crops that cause a significant loss of yield and
      deterioration in the quality of the grain. The present study investigated the
      effects of acivicin, a glutamine amino acid analog, on the physiology of various
      phytopathogenic fungi. Application of acivicin to a fungal culture and conidial
      suspension reduced mycotoxin production by the wheat scab fungus and the severity
      of rice blast, respectively. These results suggest the possibility that acivicin
      may serve as a lead compound to develop agricultural chemicals for the control of
      some plant diseases.

PMID- 24863675
TI  - Susceptibility of Tuta absoluta (Lepidoptera: Gelechiidae) Brazilian populations
      to ryanodine receptor modulators.
AB  - BACKGROUND: Phthalic and anthranilic diamides comprise a new insecticide class
      recently registered in Brazil to control Lepidoptera such as Tuta absoluta
      (Meyrick). Therefore, the baseline of susceptibility was determined for eight
      representative field populations of this species to establish a resistance
      monitoring programme. The potential for cross-resistance as well as
      detoxification metabolism was assessed in order to fine-tune the resistance
      management programme. RESULTS: Brazilian populations were very susceptible to
      chlorantraniliprole (LC50 values varied from 3.17 to 29.64 ug AI L(-1) ),
      cyantraniliprole (LC50 values varied from 8.61 to 28.95 ug AI L(-1) ) and
      flubendiamide (LC50 values varied from 94 to 230 ug AI L(-1) ), with respective
      resistance ratios of 9.33-, 3.36- and 2.45-fold between most susceptible and
      tolerant populations. Anthranilic diamides showed significant correlations
      between log LC50 values among themselves, suggesting a high risk of cross
      resistance. However, the log LC50 values of T. absoluta to phthalic diamide did
      not show any correlation with anthranilic diamides. Cytochrome- P450-dependent
      monooxygenase activity showed a weak correlation with log LC50 values of T.
      absoluta populations to anthranilic diamides, which suggests a potential route
      for evolving resistance to anthranilic diamides. CONCLUSION: The diamides were
      highly effective against T. absoluta, with populations showing a homogeneous
      response to them. Cross-resistance is very likely between anthranilic diamides in
      T. absoluta. Populations of this pest may evolve resistance by increasing
      cytochrome- P450-dependent monooxygenases.

PMID- 24863677
TI  - Predictive factors for quality of life after tonsillectomy among adults with
      recurrent pharyngitis: a prospective cohort study.
AB  - OBJECTIVES: To assess health-related quality of life (QoL) and clinical factors
      predicting it after tonsillectomy among adult patients with recurrent
      pharyngitis. DESIGN: Prospective cohort design. SETTING: Tertiary referral
      centre. PARTICIPANTS: Adults (n = 153) who underwent tonsillectomy for recurrent
      pharyngitis. MAIN OUTCOME MEASURES: QoL 6 months after tonsillectomy measured by
      the Glasgow Benefit Inventory (GBI). Factors predicting high postoperative QoL
      were sought using multiple linear regression analysis. RESULTS: Of the 142
      patients (93% of all eligible) responding to the GBI questionnaire, 94 (66%) were
      female; median age was 26 years (range 14-65). GBI Total Scores varied markedly
      (range -19 to +69), but on average showed improvement (median +27, interquartile
      range 18-36), most evidently in the GBI Physical Health Score (median +83), after
      tonsillectomy. Among routinely recorded clinical characteristics, the number of
      prior pharyngitis episodes, frequent throat pain, untreated dental caries and
      chronically infected tonsils made up the optimal subset of factors for predicting
      the GBI Total Score. However, in a random sample of patients (n = 56) for whom
      preoperative diary-based data were also available, somewhat better predictive
      ability was achieved based on just two diary items: number of days with throat
      pain and with fever during the preceding few months (correlation coefficient, r,
      between observed and fitted scores improved from 0.39 to 0.55). Yet, the
      precision of even these predictions was still quite low. CONCLUSIONS: Adult
      patients with recurrent pharyngitis were on average satisfied after
      tonsillectomy, regardless of the aetiology of the episodes. Clinical factors
      rather modestly predicted which patients benefited most from the operation.

PMID- 24863678
TI  - George Garratty, PhD, FIBMS, FRCPath, 1935-2014.

PMID- 24863679
TI  - A new mechanism for hydroxyl radical production in irradiated nanoparticle
      solutions.
AB  - The absolute yield of hydroxyl radicals per unit of deposited X-ray energy is
      determined for the first time for irradiated aqueous solutions containing metal
      nanoparticles based on a "reference" protocol. Measurements are made as a
      function of dose rate and nanoparticle concentration. Possible mechanisms for
      hydroxyl radical production are considered in turn: energy deposition in the
      nanoparticles followed by its transport into the surrounding environment is
      unable to account for observed yield whereas energy deposition in the water
      followed by a catalytic-like reaction at the water-nanoparticle interface can
      account for the total yield and its dependence on dose rate and nanoparticle
      concentration. This finding is important because current models used to account
      for nanoparticle enhancement to radiobiological damage only consider the primary
      interaction with the nanoparticle, not with the surrounding media. Nothing about
      the new mechanism appears to be specific to gold, the main requirements being the
      formation of a structured water layer in the vicinity of the nanoparticle
      possibly through the interaction of its charge and the water dipoles. The massive
      hydroxyl radical production is relevant to a number of application fields,
      particularly nanomedicine since the hydroxyl radical is responsible for the
      majority of radiation-induced DNA damage. 

PMID- 24863680
TI  - Is metabolic rate a universal 'pacemaker' for biological processes?
AB  - A common, long-held belief is that metabolic rate drives the rates of various
      biological, ecological and evolutionary processes. Although this metabolic
      pacemaker view (as assumed by the recent, influential 'metabolic theory of
      ecology') may be true in at least some situations (e.g. those involving moderate
      temperature effects or physiological processes closely linked to metabolism, such
      as heartbeat and breathing rate), it suffers from several major limitations,
      including: (i) it is supported chiefly by indirect, correlational evidence (e.g.
      similarities between the body-size and temperature scaling of metabolic rate and
      that of other biological processes, which are not always observed) - direct,
      mechanistic or experimental support is scarce and much needed; (ii) it is
      contradicted by abundant evidence showing that various intrinsic and extrinsic
      factors (e.g. hormonal action and temperature changes) can dissociate the rates
      of metabolism, growth, development and other biological processes; (iii) there
      are many examples where metabolic rate appears to respond to, rather than drive
      the rates of various other biological processes (e.g. ontogenetic growth, food
      intake and locomotor activity); (iv) there are additional examples where
      metabolic rate appears to be unrelated to the rate of a biological process (e.g.
      ageing, circadian rhythms, and molecular evolution); and (v) the theoretical
      foundation for the metabolic pacemaker view focuses only on the energetic control
      of biological processes, while ignoring the importance of informational control,
      as mediated by various genetic, cellular, and neuroendocrine regulatory systems.
      I argue that a comprehensive understanding of the pace of life must include how
      biological activities depend on both energy and information and their
      environmentally sensitive interaction. This conclusion is supported by extensive
      evidence showing that hormones and other regulatory factors and signalling
      systems coordinate the processes of growth, metabolism and food intake in
      adaptive ways that are responsive to an organism's internal and external
      conditions. Metabolic rate does not merely dictate growth rate, but is coadjusted
      with it. Energy and information use are intimately intertwined in living systems:
      biological signalling pathways both control and respond to the energetic state of
      an organism. This review also reveals that we have much to learn about the
      temporal structure of the pace of life. Are its component processes highly
      integrated and synchronized, or are they loosely connected and often discordant?
      And what causes the level of coordination that we see? These questions are of
      great theoretical and practical importance. 

PMID- 24863681
TI  - A meta-analysis of imitation abilities in individuals with autism spectrum
      disorders.
AB  - Although imitation impairments are often reported in individuals with autism
      spectrum disorders (ASD), previous work has not yet determined whether these
      impairments are significant, specific to ASD, and present across the entire
      spectrum. This report of 53 studies on imitation in ASD seeks to determine
      whether individuals with ASD show significant imitation deficits, the magnitude
      of these deficits, and whether they are specific to ASD. Using standard meta
      analytic techniques in a random-effects model, the data reviewed suggest that
      individuals with ASD show deficits in imitation, performing on average 0.81 SDs
      below individuals without ASD on imitation tasks. This deficit was specific to
      the condition of having ASD. Moderator analyses revealed that the average Autism
      Diagnostic Observation Schedule (ADOS) scores of groups of ASD participants were
      significantly and strongly negatively associated with the imitation abilities of
      these subjects, but average participant IQ was not associated with imitation
      abilities. Study setting, novelty of actions, format of imitation tasks (live vs.
      not), number of actions to imitate, or verbal prompts were not found to
      significantly affect the sizes of the imitation differences between individuals
      with and without ASD. The manner in which imitation was operationalized, however,
      had significant effects on whether imitation deficits were found between
      individuals with and without ASD. In tests that measured imitation of both form
      and end points, participants with ASD showed significant deficits compared with
      those without ASD; on tests of end point emulation only, individuals with ASD
      showed no deficits.

PMID- 24863682
TI  - Analysis of pathological complete response rates with paclitaxel-based regimens
      in trimodality therapy for esophageal cancer.
AB  - The study aimed to examine whether omission of 5-fluorouracil (5-FU)-containing
      chemotherapy alters pathological complete response rates in patients receiving
      trimodality therapy for locally advanced esophageal cancer. A total of 159
      patients were identified. One hundred twenty-nine patients received platinum/5-FU
      concurrently with radiotherapy, and 30 received taxane/platinum-containing
      chemoradiotherapy prior to esophagectomy. Patients were staged using the 2002
      American Joint Committee on Cancer staging system. Patients were matched between
      chemotherapeutic groups, with no significant demographic or clinical differences
      other than T stage (14% T2 in the 5-FU group; no T2 in the platinum/taxane group)
      and radiotherapy technique (8.5% received intensity-modulated radiotherapy in the
      5-FU group; 60% in the platinum/taxane group). Pathological complete response
      rates for 5-FU and platinum/taxane-based groups were not significantly different
      (45% and 30%, respectively; P = 0.1548). Five-year overall survival and
      progression-free survival were not statistically different between the two
      groups. Significant predictors of pathological complete response included N stage
      (56% N0 and 33% N1; P = 0.0083), histology (37% adenocarcinoma and 59% squamous
      cell; P = 0.0123), tumor location (39% distal and 59% proximal/mid; P = 0.048),
      gastroesophageal junction involvement (33% involved and 55% uninvolved; P =
      0.005), and radiotherapy end-to-surgery interval (50% < 55 days and 34% >= 55
      days; P = 0.04). Grades 3-4 hematological toxicity was higher in the 5-FU group
      (36%) than in the paclitaxel-containing therapy group (17%; P = 0.0484). Use of
      paclitaxel-containing chemoradiotherapy did not result in inferior pathological
      complete response, overall survival, or progression-free survival rates, and
      resulted in less hematological toxicity than 5-FU treatment. 

PMID- 24863683
TI  - Postacute effects of kisspeptin-10 on neuronal injury induced by L-methionine in
      rats.
AB  - Apart from its effect on the regulation of reproductive function, recent studies
      indicate that kisspeptin may play roles in the antioxidant defense system. The
      antioxidant defense system and oxidative stress contribute to the etiology and
      pathogenesis of neuronal cell death after brain injury. We have investigated the
      postacute effect of kisspeptin-10 on brain injury induced by L-methionine. DNA
      fragmentation, malondialdehyde (MDA), reduced glutathione levels, and superoxide
      dismutase (SOD) activities were analyzed. Our results showed that methionine
      treatment increases apoptotic cell death. Kisspeptin alone showed no side effect
      on apoptotic cell death. However, kisspeptin treatment reversed the proapoptotic
      effect of methionine associated with reduced MDA and increased glutathione
      levels. Furthermore, SOD activity was completely depleted in methionine-treated
      animals. In conclusion, our results revealed that delayed kisspeptin-10 treatment
      reduces neuronal cell death by activation of SOD activity.

PMID- 24863684
TI  - Detergent screening of the human voltage-gated proton channel using fluorescence
      detection size-exclusion chromatography.
AB  - The human voltage-gated proton channel (Hv1) is a membrane protein consisting of
      four transmembrane domains and intracellular amino- and carboxy-termini. The
      protein is activated by membrane depolarization, similar to other voltage
      sensitive proteins. However, the Hv1 proton channel lacks a traditional ion pore.
      The human Hv1 proton channel has been implicated in mediating sperm capacitance,
      stroke, and most recently as a biomarker/mediator of cancer metastasis. Recently,
      the three-dimensional structures for homologues of this voltage-gated proton
      channel were reported. However, it is not clear what artificial environment is
      needed to facilitate the isolation and purification of the human Hv1 proton
      channel for structural study. In the present study, we generated a chimeric
      protein that placed an enhanced green fluorescent protein (EGFP) to the amino
      terminus of the human Hv1 proton channel (termed EGFP-Hv1). The chimeric protein
      was expressed in a baculovirus expression system using Sf9 cells and subjected to
      detergent screening using fluorescence-detection size-exclusion chromatography.
      The EGFP-Hv1 proton channel can be solubilized in the zwitterionic detergent
      Anzergent 3-12 and the nonionic n-dodecyl-beta-d-maltoside (DDM) with little
      protein aggregation and a prominent monomeric protein peak at 48 h postinfection.
      Furthermore, we demonstrate that the chimeric protein exhibits a monomeric
      protein peak, which is distinguishable from protein aggregates, at the final size
      exclusion chromatography purification step. Taken together, we can conclude that
      solubilization in DDM will provide a useable final product for further structural
      characterization of the full-length human Hv1 proton channel. 

PMID- 24863685
TI  - Reliability and validity of two in vivo measurements for skin surface topography
      in aged adults.
AB  - BACKGROUND: The non-contact optical methods phaseshift rapid in vivo measurement
      of skin (PRIMOS) and surface evaluation of living skin (SELS) are widely applied
      for measuring skin surface topography. The aims of the present study were to
      evaluate reliability and validity of these methods and to compare skin roughness
      intraindividually. METHODS: SELS and PRIMOS measurements were performed on four
      skin areas of the left and right volar forearms in 12 healthy elderly subjects.
      Reliability and correlations were analyzed for Visioscan(r) and PRIMOS roughness
      parameters. Student's t-tests for estimating differences between contralateral
      volar forearm sites were applied. RESULTS: ICC coefficients of the Visioscan(r)
      roughness estimates ranged between 0.50 and 0.95 and of the PRIMOS measurements
      between 0.01 and 1.00. The Visioscan(r) parameters SEr, SEsm, Rmax, and Rz, and
      the PRIMOS parameters Ra, Rz, Smax, Wt, and Sz showed most significant
      correlations with each other and to additional roughness parameters. Mean
      roughness differences between contralateral forearm skin areas ranged between 0.0
      (SEsc) and 6.7 (Rmax). CONCLUSIONS: The Visioscan(r) parameters SEr, Rmax, and Rz
      showed most reliable and valid values and were largely comparable on
      contralateral forearm skin sites in elderly subjects. Rmax, Rz, and Ra should be
      preferred for measuring skin surface topography with PRIMOS.

PMID- 24863686
TI  - Galvanic replacement-free deposition of Au on Ag for core-shell nanocubes with
      enhanced chemical stability and SERS activity.
AB  - We report a robust synthesis of Ag@Au core-shell nanocubes by directly depositing
      Au atoms on the surfaces of Ag nanocubes as conformal, ultrathin shells. Our
      success relies on the introduction of a strong reducing agent to compete with and
      thereby block the galvanic replacement between Ag and HAuCl4. An ultrathin Au
      shell of 0.6 nm thick was able to protect the Ag in the core in an oxidative
      environment. Significantly, the core-shell nanocubes exhibited surface plasmonic
      properties essentially identical to those of the original Ag nanocubes, while the
      SERS activity showed a 5.4-fold further enhancement owing to an improvement in
      chemical enhancement. The combination of excellent SERS activity and chemical
      stability may enable a variety of new applications. 

PMID- 24863687
TI  - A plant cell division algorithm based on cell biomechanics and ellipse-fitting.
AB  - BACKGROUND AND AIMS: The importance of cell division models in cellular pattern
      studies has been acknowledged since the 19th century. Most of the available
      models developed to date are limited to symmetric cell division with isotropic
      growth. Often, the actual growth of the cell wall is either not considered or is
      updated intermittently on a separate time scale to the mechanics. This study
      presents a generic algorithm that accounts for both symmetrically and
      asymmetrically dividing cells with isotropic and anisotropic growth. Actual
      growth of the cell wall is simulated simultaneously with the mechanics. METHODS:
      The cell is considered as a closed, thin-walled structure, maintained in tension
      by turgor pressure. The cell walls are represented as linear elastic elements
      that obey Hooke's law. Cell expansion is induced by turgor pressure acting on the
      yielding cell-wall material. A system of differential equations for the positions
      and velocities of the cell vertices as well as for the actual growth of the cell
      wall is established. Readiness to divide is determined based on cell size. An
      ellipse-fitting algorithm is used to determine the position and orientation of
      the dividing wall. The cell vertices, walls and cell connectivity are then
      updated and cell expansion resumes. Comparisons are made with experimental data
      from the literature. KEY RESULTS: The generic plant cell division algorithm has
      been implemented successfully. It can handle both symmetrically and
      asymmetrically dividing cells coupled with isotropic and anisotropic growth
      modes. Development of the algorithm highlighted the importance of ellipse-fitting
      to produce randomness (biological variability) even in symmetrically dividing
      cells. Unlike previous models, a differential equation is formulated for the
      resting length of the cell wall to simulate actual biological growth and is
      solved simultaneously with the position and velocity of the vertices.
      CONCLUSIONS: The algorithm presented can produce different tissues varying in
      topological and geometrical properties. This flexibility to produce different
      tissue types gives the model great potential for use in investigations of plant
      cell division and growth in silico.

PMID- 24863688
TI  - The management of pineal tumors as a model for a multidisciplinary approach in
      neuro-oncology.
AB  - The management of pineal tumors is a model for multidisciplinarity. Apart from an
      emergency situation that requires immediate shunting of cerebrospinal fluid
      (CSF), the initial discussion should involve at least a radiologist, a surgeon, a
      neurologist and an oncologist. The initial decision is whether obtaining a
      histological proof is obligatory. It depends on age and ethnicity, site (mono- or
      bifocality), presence of markers in serum as well as CSF, and/or of malignant
      cells in the CSF. In cases of marker elevation indicating a germ cell tumor,
      front line chemotherapy can avoid dangerous immediate surgery. When histological
      proof is required, the extent of surgery should be discussed, aiming either only
      at obtaining tissue or removal. If a germ cell tumor is detected, treatment will
      include a cisplatin-containing chemotherapy followed by focal or ventricular
      irradiation. Tumors of the pineal parenchyma will be treated according to grade,
      either by surgery alone (pinealocytoma) or chemo-radiotherapy (pinealoblastomas).
      Similarly, gliomas will be treated depending on their grade with several
      different possible lines in low grade, and usually radio-chemotherapy in high
      grade. A careful balance between improved survival rates and decreased long-term
      side effects will guide the decisions of all these specialists. 

PMID- 24863689
TI  - Supracerebellar infratentorial approach for pineal region tumors: Our surgical
      and technical considerations.
AB  - The infratentorial supracerebellar approach is most widely used for pineal
      tumors. We report our own experience and technical considerations using this
      approach. MATERIAL: From 1982 to 2010, we operated on 232 patients with pineal
      region tumors. Of these, 201 patients were operated on using a suboccipital
      transtentorial approach while 31 patients were operated on using a
      supracerebellar infratentorial approach. The median age of the patients ranged
      between 8 months and 74 years. There were 19 children and 12 adults. All patients
      presented with elevated intracranial pressure. There were 6 pinealocytomas, 3
      papillary tumors, 7 germinomas, 2 benign teratomas, 4 pineal cysts and 9 gliomas.
      Adjuvant post-surgical therapy consisted of chemo-radiotherapy in 4 patients, 2
      with germinomas and 2 with a grade II/III gliomas. Radiotherapy was performed in
      the other twelve patients (5 germinomas and 7 gliomas). RESULTS AND
      COMPLICATIONS: All patients are still alive at a median follow-up of eight years.
      Twelve of the 19 children are attending normal school classes for their age, 5
      are attending classes for special needs children and 2 are not yet of school age
      at the last follow-up. Seven of the 12 adults are working normally, three are
      working part-time at the same job and two have retired but are able to lead a
      normal life. Postoperative complications included symptomatic diffuse cerebellar
      edema (one patient) completely resolved with a mild residual cerebellar syndrome;
      double vision secondary to IV nerve palsy (one patient); transitory Parinaud's
      syndrome (2 patients) and cerebellar gait (2 patients) nearly completely
      recovered at respectively six and twelve months. CONCLUSION: The supracerebellar
      infratentorial approach seems to be a safe and effective choice in the treatment
      of pineal region tumors. In our experience, it permits complete tumor resections
      with acceptable morbidity and all neurosurgeons should master this approach in
      order to adapt their surgical choice according to size, extent and the
      relationship of the lesion with the surrounding anatomical structures.

PMID- 24863690
TI  - Rapid and complete hematological response of refractory hairy cell leukemia to
      the BRAF inhibitor dabrafenib.

PMID- 24863691
TI  - The long-term results of childhood acute lymphoblastic leukemia at two centers
      from Turkey: 15 years of experience with the ALL-BFM 95 protocol.
AB  - Dramatic progress in the treatment of childhood acute lymphoblastic leukemia
      (ALL) has been achieved during the last two decades in Western countries, where
      the 5-year event-free survival (EFS) rate has risen from 30 to 85 %. However,
      similarly high cure rates have not always been achieved in all centers in
      developing countries due to limited sources. We evaluated the treatment results
      of the ALL-Berlin-Frankfurt-Munster (BFM) 95 protocol as used between 1995 and
      2009 in the pediatric hematology departments of two university hospitals. A
      retrospective analysis of 343 children newly diagnosed with ALL (M/F 200/143,
      median age 6.8 years) was performed. The overall survival (OS) and EFS according
      to age, initial leukocyte count, immunophenotype, chemotherapy responses (on days
      8, 15, and 33), and risk groups were analyzed by Kaplan-Meier survival analysis.
      Median follow-up time was 6.4 years. Complete remission was achieved in 97 % of
      children. Five-year EFS and OS were found to be 78.4 and 79.9 %, respectively.
      Children younger than 6 years old had significantly better EFS and OS (83.7 and
      85.2 %) than children aged >=6 years (71.4 and 72.8 %). Adolescents achieved 63 %
      EFS and 65 % OS. Patients who had initial leukocyte counts of <20 * 10(9)/L had
      better EFS and OS (82.2 and 84.6 %) than children with higher initial leukocyte
      counts (72.6 and 72.6 %). EFS for B-cell precursor and T-cell ALL was 81.5 and
      66.7 %, respectively. Children with a good response to prednisolone on day 8 (87
      %) achieved significantly better EFS and OS (81.2 and 81.9 % vs. 55.3 and 60.5
      %). Children whose bone marrow on day 15 was in complete remission had higher EFS
      and OS (83.7 and 86.6.1 % vs. 56.4 and 61.5 %). Children in the standard-risk and
      medium-risk groups obtained statistically significantly higher EFS (95.5 and 82.7
      %) and OS (97.7 and 82.3 %) compared to the high-risk group (EFS 56.3 %, OS 63.4
      %). The relapse rate was 14.8 %. The median relapse time from diagnosis was 23.2
      months. Death occurred in 69 of 343 patients (20.1 %). The major causes of death
      were infection and relapse. None of the patients died of drug-related toxicity.
      The ALL-BFM 95 protocol was applied successfully in these two centers. In
      developing countries in which minimal residual disease cannot be monitored, this
      protocol can still be used with high survival rates.

PMID- 24863693
TI  - Azacitidine as the post-remission therapy for elderly patients with acute myeloid
      leukemia.

PMID- 24863692
TI  - ESHAP as salvage therapy for relapsed or refractory Hodgkin's lymphoma.
AB  - The management of relapsed or refractory Hodgkin's lymphoma (RR-HL) remains a
      challenge for hematologists and oncologists. Salvage chemotherapy followed by
      autologous stem cell transplantation (ASCT) is the standard of care for RR-HL.
      However, one of the most controversial aspects is which the best salvage protocol
      could be. We retrospectively analyzed 82 consecutive RR-HL who received
      etoposide, steroids, ara-C, and cisplatin (ESHAP) as salvage therapy followed by
      ASCT. Fifty percent of patients were refractory and 23 % early relapses. Overall
      response rate (ORR) was 67 % (50 % complete remission (CR)). Ninety one percent
      of patients (75/82) were transplanted. With a mean follow-up of 87 +/- 53 months,
      the median progression-free survival (PFS) and time to tumor progression (TTP)
      for the whole population were 52 and 56 months, respectively, and the 5-year
      overall survival was 72.6 %. Achieving CR after ESHAP was associated with a
      longer PFS (78 vs 16 % 5-year PFS, respectively, P < 0.01) and TTP (80 vs 19 % 5
      year TTP, respectively, P < 0.01). However, there were no differences for overall
      survival (OS) when comparing CR and partial response (PR) after ESHAP. Toxicity
      was low and <10 % of patients developed neutropenic fever, with no toxic deaths.
      Mobilization was possible in 94 % of patients. ESHAP is a safe and efficient
      therapeutic option for patients with RR-HL who are candidates for ASCT, since it
      combines a high response rate and mobilizing potential with a low toxicity
      profile.

PMID- 24863694
TI  - Protective effects of the thioredoxin and glutaredoxin systems in dopamine
      induced cell death.
AB  - Although the etiology of sporadic Parkinson disease (PD) is unknown, it is well
      established that oxidative stress plays an important role in the pathogenic
      mechanism. The thioredoxin (Trx) and glutaredoxin (Grx) systems are two central
      systems upholding the sulfhydryl homeostasis by reducing disulfides and mixed
      disulfides within the cell and thereby protecting against oxidative stress. By
      examining the expression of redox proteins in human postmortem PD brains, we
      found the levels of Trx1 and thioredoxin reductase 1 (TrxR1) to be significantly
      decreased. The human neuroblastoma cell line SH-SY5Y and the nematode
      Caenorhabditis elegans were used as model systems to explore the potential
      protective effects of the redox proteins against 6-hydroxydopamine (6-OHDA)
      induced cytotoxicity. 6-OHDA is highly prone to oxidation, resulting in the
      formation of the quinone of 6-OHDA, a highly reactive species and powerful
      neurotoxin. Treatment of human cells with 6-OHDA resulted in an increased
      expression of Trx1, TrxR1, Grx1, and Grx2, and small interfering RNA for these
      genes significantly increased the cytotoxic effects exerted by the 6-OHDA
      neurotoxin. Evaluation of the dopaminergic neurons in C. elegans revealed that
      nematodes lacking trxr-1 were significantly more sensitive to 6-OHDA, with
      significantly increased neuronal degradation. Importantly, both the Trx and the
      Grx systems were also found to directly mediate reduction of the 6-OHDA-quinone
      in vitro and thus render its cytotoxic effects. In conclusion, our results
      suggest that the two redox systems are important for neuronal survival in
      dopamine-induced cell death. 

PMID- 24863695
TI  - ESR evidence for in vivo formation of free radicals in tissue of mice exposed to
      single-walled carbon nanotubes.
AB  - Nanomaterials are being utilized in an increasing variety of manufactured goods.
      Because of their unique physicochemical, electrical, mechanical, and thermal
      properties, single-walled carbon nanotubes (SWCNTs) have found numerous
      applications in the electronics, aerospace, chemical, polymer, and pharmaceutical
      industries. Previously, we have reported that pharyngeal exposure of C57BL/6 mice
      to SWCNTs caused dose-dependent formation of granulomatous bronchial interstitial
      pneumonia, fibrosis, oxidative stress, acute inflammatory/cytokine responses, and
      a decrease in pulmonary function. In the current study, we used electron spin
      resonance (ESR) to directly assess whether exposure to respirable SWCNTs caused
      formation of free radicals in the lungs and in two distant organs, the heart and
      liver. Here we report that exposure to partially purified SWCNTs (HiPco
      technique, Carbon Nanotechnologies, Inc., Houston, TX, USA) resulted in the
      augmentation of oxidative stress as evidenced by ESR detection of alpha-(4
      pyridyl-1-oxide)-N-tert-butylnitrone spin-trapped carbon-centered lipid-derived
      radicals recorded shortly after the treatment. This was accompanied by a
      significant depletion of antioxidants and elevated biomarkers of inflammation
      presented by recruitment of inflammatory cells and an increase in proinflammatory
      cytokines in the lungs, as well as development of multifocal granulomatous
      pneumonia, interstitial fibrosis, and suppressed pulmonary function. Moreover,
      pulmonary exposure to SWCNTs also caused the formation of carbon-centered lipid
      derived radicals in the heart and liver at later time points (day 7
      postexposure). Additionally, SWCNTs induced a significant accumulation of
      oxidatively modified proteins, increase in lipid peroxidation products, depletion
      of antioxidants, and inflammatory response in both the heart and the liver.
      Furthermore, the iron chelator deferoxamine noticeably reduced lung inflammation
      and oxidative stress, indicating an important role for metal-catalyzed species in
      lung injury caused by SWCNTs. Overall, we provide direct evidence that lipid
      derived free radicals are a critical contributor to tissue damage induced by
      SWCNTs not only in the lungs, but also in distant organs. 

PMID- 24863697
TI  - Regional lymphatic recurrence after salvage surgery for ipsilateral breast tumor
      recurrence of breast cancer without local treatment for regional lymphatic basin.
AB  - BACKGROUND: There is limited information regarding rates of and risk factors for
      regional lymphatic recurrence (RLR) after salvage surgery for ipsilateral breast
      tumor recurrence (IBTR) without local treatment for the regional lymphatic basin.
      METHODS: One hundred two patients, who underwent salvage breast surgery without
      local treatment for the regional lymphatic basin (surgery or radiotherapy) for
      IBTR that relapsed after breast-conserving surgery for primary breast cancer,
      were reviewed retrospectively to examine the rate of and risk factors for RLR.
      RESULTS: Of the 102 patients, 9 patients (8.8%) had RLR with a median follow-up
      period of 3.7 years after salvage breast surgery for IBTR. The estrogen receptor
      (ER) status and lymphovascular invasion of the recurrent breast tumor were both
      independent predictive factors of RLR (P = 0.04 and 0.02, respectively).
      CONCLUSIONS: The rate of RLR was not low in patients with IBTR who received
      salvage breast surgery only without any treatment for the regional lymphatic
      basin. The ER status and lymphovascular invasion of the recurrent breast tumor
      were predictive factors of RLR.

PMID- 24863696
TI  - The metastatic potential of triple-negative breast cancer is decreased via
      caloric restriction-mediated reduction of the miR-17~92 cluster.
AB  - Caloric restriction (CR) has been shown to cause tumor regression in models of
      triple-negative breast cancer (TNBC), and the regression is augmented when
      coupled with ionizing radiation (IR). In this study, we sought to determine if
      the molecular interaction between CR and IR could be mediated by microRNA (miR).
      miR arrays revealed 3 miRs in the miR-17~92 cluster as most significantly down
      regulated when CR is combined with IR. In vivo, CR and IR down regulated miR
      17/20 in 2 TNBC models. To elucidate the mechanism by which this cluster
      regulates the response to CR, cDNA arrays were performed and the top 5
      statistically significant gene ontology terms with high fold changes were all
      associated with extracellular matrix (ECM) and metastases. In silico analysis
      revealed 4 potential targets of the miR-17~92 cluster related to ECM: collagen 4
      alpha 3, laminin alpha 3, and metallopeptidase inhibitors 2 and 3, which were
      confirmed by luciferase assays. The overexpression or silencing of miR-17/20a
      demonstrated that those miRs directly affected the ECM proteins. Furthermore, we
      found that CR-mediated inhibition of miR-17/20a can regulate the expression of
      ECM proteins. Functionally, we demonstrate that CR decreases the metastatic
      potential of cells which further demonstrates the importance of the ECM. In
      conclusion, CR can be used as a potential treatment for cancer because it may
      alter many molecular targets concurrently and decrease metastatic potential for
      TNBC. 

PMID- 24863698
TI  - Laser light scan analysis of the "anticonvulsant face".
AB  - BACKGROUND: The "anticonvulsant face," with a short nose, broad nasal bridge,
      epicanthal folds, and wide mouth, was described in the 1970s in children who had
      been exposed during pregnancy to the anticonvulsant drugs phenytoin and
      phenobarbital. The laser light scan makes it possible to establish three
      dimensional positions of physical features and to determine more objectively the
      changes in the size and shape of the affected soft tissues of the faces of
      children exposed to these anticonvulsant drugs during pregnancy. METHODS:
      Thirteen individuals, exposed throughout pregnancy to phenytoin as either
      monotherapy or polytherapy, were identified in a previous analysis as having
      significant changes in their craniofacial features based on measurements of
      cephalometric radiographs. Those changes were associated with midface hypoplasia
      and a short nose, features of the "anticonvulsant face." The soft tissues of
      their faces have been evaluated with laser light scans. RESULTS: The notable
      changes in soft tissues identified by laser light scans were a wide philtrum (cph
      cph), narrow mouth (ch-ch), short nasal bridge (n-prn), shortened nose height (n
      sn), and flattened orbits (orbital protrusion index). CONCLUSION: This analysis
      of the facial features of phenytoin-exposed individuals, selected because of
      changes in their craniofacial bony structures, showed that there were several
      significant changes, two of which, widening of the philtrum and a small mouth,
      have not been described previously as part of this phenotype.

PMID- 24863699
TI  - Assessment of pulmonary vascular reactivity to oxygen using fractional moving
      blood volume in fetuses with normal lung development and pulmonary hypoplasia in
      congenital diaphragmatic hernia.
AB  - OBJECTIVE: The objective of this study is to evaluate whether assessment
      pulmonary vascular reactivity in response to maternal hyperoxygenation using
      fractional moving blood volume (FMBV) is associated with lesser variability
      between individual measurements than what is observed with direct Doppler
      measurements. STUDY DESIGN: Forty-five measurements were performed in 15
      singleton fetuses with normal lung development at three time points in the latter
      half of pregnancy (range: 25.9-36.7 weeks). We further evaluated five fetuses
      with severe congenital diaphragmatic hernia. Lung perfusion was assessed using
      power Doppler ultrasound, and images were stored for offline FMBV calculation,
      both at base line and during oxygen administration (9 L/min for 10 min). The
      proportionate difference between both measurements is further referred to as
      deltaFMBV. RESULTS: Overall, 91% of images were of sufficient quality for further
      analysis. There was no correlation between pulmonary reactivity to oxygen
      (deltaFMBV) and gestational age in controls (12.9 +/- 32.1%). Moreover, deltaFMBV
      showed large variability between subjects, as well as within the same fetus
      throughout gestation. We observed good intraobserver (0.88; 0.84) and
      interobserver (0.88; 0.77) reproducibility for both controls and congenital
      diaphragmatic hernia, respectively (intraclass correlation coefficients).
      CONCLUSION: Despite being a reproducible method to study the lung vasculature,
      the large variability of FMBV following hyperoxygenation limits its clinical
      translation.

PMID- 24863700
TI  - High-frequency ultrasonography but not 930-nm optical coherence tomography
      reliably evaluates melanoma thickness in vivo: a prospective validation study.
AB  - BACKGROUND: Early diagnosis and rapid surgical excision are essential for
      improving the prognosis of patients with melanoma. Reflectance confocal
      microscopy has been validated as a feasible procedure for in vivo diagnosis of
      melanoma but cannot be used to measure tumour thickness. However, ultrasonography
      and optical coherence tomography may allow melanoma thickness to be measured in
      vivo. OBJECTIVES: To validate the accuracy and reliability of high-frequency
      ultrasonography (HFUS) and optical coherence tomography for assessing melanoma
      thickness in vivo. METHODS: We conducted a prospective study on 131 patients with
      at least one equivocal melanocytic lesion. Each lesion underwent optical
      coherence tomography and HFUS assessment, followed by excision and pathological
      examination. Histopathology was considered to be the gold standard for assessing
      melanoma thickness. Repeatability, inter- and intrarater reproducibility and
      reliability were evaluated for each imaging procedure. RESULTS: Ultrasonography
      showed a good level of agreement with histology [intraclass correlation
      coefficient (ICC) 0.807; 95% confidence interval (CI) 0.703-0.877] and excellent
      inter-rater reproducibility (G = 0.97), resulting in reliable in vivo assessment
      of melanoma thickness. The 930-nm optical coherence tomography showed a poor
      level of agreement with histopathology (ICC 0.0; 95% CI -0.2-0.2) and the inter
      rater reproducibility was null (G = 0.00). CONCLUSIONS: HFUS is a reliable and
      reproducible noninvasive method for assessing melanoma thickness. Routine use of
      HFUS may allow single-step excision of equivocal melanocytic lesions, with
      surgical margins determined by in vivo assessment of tumour thickness.

PMID- 24863702
TI  - [Unintentional injuries in the German adult population. Results of the "German
      Health Update" survey 2010].
AB  - In Germany, more than 20,000 people were killed in accidents and 8.7 million
      people suffered nonfatal unintentional injuries (UI) in 2011. This report gives
      an overview of the occurrence of nonfatal UI in the German adult population. The
      representative health survey "German Health Update" 2010 (phone survey) collected
      data on nonfatal accidents in the adult population within a recall period of 12
      months (n = 22,050). Interviewees reporting medically treated UI responded to 19
      further questions about accident locations, accident mechanisms, injuries, and
      consequences of up to three UI within 1 year. Overall, detailed data on 2,117 UI
      were collected. About 7.9 % of the German adult population suffers at least one
      medically treated UI within 1 year. Men are more often affected than women and
      young people more frequently than older people. The majority of all UI occurs at
      home or during leisure-time activities. One in five UI results from accidents on
      public footways, roads, and squares. Falls account for almost every third UI and
      about one in five accidents causes fractures. Two thirds of all UI require
      inpatient treatment. Two in three UI lead to temporary sick leave averaging 29.7
      days of absenteeism. Among UI at home and in leisure-time activities, falls have
      particularly serious consequences. Moreover, falls play an important role in UI
      among pedestrians and cyclists. UI affect large parts of the German adult
      population and are clearly patterned by gender, age, and accident location.
      Therefore, prevention activities should consider target group-specific needs and
      setting-specific circumstances of UI. 

PMID- 24863703
TI  - [Unintentional injuries among children and adolescents in Germany. Data sources
      and results].
AB  - Compared to adults, children and adolescents run a considerably higher risk of
      suffering unintentional injuries (UI). To prevent UI, detailed knowledge of the
      overall accident occurrence and the determinants of UI is needed. This article
      gives an overview of the data sources covering the occurrence of UI among
      children and adolescents in Germany. According to the Robert Koch Institute's
      German Health Interview and Examination Survey for Children and Adolescents
      (KiGGS), approximately 15.3 % of children and adolescents (1-17 years) in Germany
      suffer at least one UI within 12 months. Most accidents (60.7 %) occur at home or
      during leisure-time activities. In 2011, the German Statutory Accident Insurance
      (DGUV) registered more than 1.4 million accidents among children in day-care
      facilities and students in educational institutions. According to official
      statistics, in the same year, more than 50,000 children and adolescents were
      injured in traffic accidents. Moreover, the Federal Statistical Office registered
      260,534 hospital admissions due to injuries and poisonings among children and
      adolescents. All data sources revealed age- and sex-specific differences. Boys
      suffer UI more frequently than girls do and they show higher injury rates in
      adolescence than during childhood. While UI among children mostly happen at home,
      road traffic and leisure-time accidents increase in occurrence during
      adolescence. In Germany, there are numerous initiatives dedicated to the
      prevention of UI in children and adolescents. The creation of target group
      specific prevention measures is complicated by the fact that the methodological
      approaches of existing data sources differ considerably. 

PMID- 24863704
TI  - [Accidents and injuries at work].
AB  - In the case of an accident at work, the person concerned is insured by law
      according to the guidelines of the Sozialgesetzbuch VII as far as the injuries
      have been caused by this accident. The most important source of information on
      the incident in question is the accident report that has to be sent to the
      responsible institution for statutory accident insurance and prevention by the
      employer, if the accident of the injured person is fatal or leads to an
      incapacity to work for more than 3 days (= reportable accident). Data concerning
      accidents like these are sent to the Deutsche Gesetzliche Unfallversicherung
      (DGUV) as part of a random sample survey by the institutions for statutory
      accident insurance and prevention and are analyzed statistically. Thus the key
      issues of accidents can be established and used for effective prevention.
      Although the success of effective accident prevention is undisputed, there were
      still 919,025 occupational accidents in 2011, with clear gender-related
      differences. Most occupational accidents involve the upper and lower extremities.
      Accidents are analyzed comprehensively and the results are published and made
      available to all interested parties in an effort to improve public awareness of
      possible accidents. Apart from reportable accidents, data on the new occupational
      accident pensions are also gathered and analyzed statistically. Thus, additional
      information is gained on accidents with extremely serious consequences and partly
      permanent injuries for the accident victims. 

PMID- 24863705
TI  - [Sports injuries in German club sports, Aspects of epidemiology and prevention].
AB  - BACKGROUND: Almost one of four Germans is registered in a sports club. Nowadays,
      sport is acknowledged as an integral component of a healthy lifestyle. Numerous
      studies provide evidence of the benefits of sports on health. However, about 2
      million sports injuries per year diminish the health benefits of sport.
      OBJECTIVE: (a) Description of the epidemiology of sports injuries in German
      sports club between 1987 and 2012 and (b) identification of focal areas for the
      development and implementation of prevention measures. METHODS: Continuous
      questionnaire-based injury monitoring of club sports injuries that have been
      reported to the respective sports insurance. Full survey among selected federal
      sports associations. RESULTS: Since 1987, a sample of 200,884 sports injuries has
      been established. About two thirds of the injuries are reported in soccer,
      handball, basketball, and volleyball, although only one third of all sports club
      members are registered in these team sports. The number of women's soccer
      injuries has risen from 7.5 to 15.6 %. Ankle injuries have decreased from 28.7 to
      16.9 %. By contrast, the rate of knee injuries has increased from 18.4 to 20.3 %.
      Days of disability have dropped steadily since the 1990s. Inpatient hospital days
      have decreased from 10 to 5 days, whereas the share of injuries that needed
      surgery increased from 30 to 40 %. CONCLUSION: Team ball sports are still a clear
      focal area for injury prevention, as participation and injury risk are highest in
      this group. While the prevention of ankle injuries seems to be headed in the
      right direction, knee injuries are increasing. As team ball sports become more
      popular among women, who are more prone to severe knee injuries, prevention
      programs should be tailored toward the specific situation and needs of the
      targeted sports participants.

PMID- 24863701
TI  - A high-density linkage map enables a second-generation collared flycatcher genome
      assembly and reveals the patterns of avian recombination rate variation and
      chromosomal evolution.
AB  - Detailed linkage and recombination rate maps are necessary to use the full
      potential of genome sequencing and population genomic analyses. We used a custom
      collared flycatcher 50 K SNP array to develop a high-density linkage map with 37
      262 markers assigned to 34 linkage groups in 33 autosomes and the Z chromosome.
      The best-order map contained 4215 markers, with a total distance of 3132 cM and a
      mean genetic distance between markers of 0.12 cM. Facilitated by the array being
      designed to include markers from most scaffolds, we obtained a second-generation
      assembly of the flycatcher genome that approaches full chromosome sequences (N50
      super-scaffold size 20.2 Mb and with 1.042 Gb (of 1.116 Gb) anchored to and
      mostly ordered and oriented along chromosomes). We found that flycatcher and
      zebra finch chromosomes are entirely syntenic but that inversions at mean rates
      of 1.5-2.0 event (6.6-7.5 Mb) per My have changed the organization within
      chromosomes, rates high enough for inversions to potentially have been involved
      with many speciation events during avian evolution. The mean recombination rate
      was 3.1 cM/Mb and correlated closely with chromosome size, from 2 cM/Mb for
      chromosomes >100 Mb to >10 cM/Mb for chromosomes <10 Mb. This size dependence
      seemed entirely due to an obligate recombination event per chromosome; if 50 cM
      was subtracted from the genetic lengths of chromosomes, the rate per physical
      unit DNA was constant across chromosomes. Flycatcher recombination rate showed
      similar variation along chromosomes as chicken but lacked the large interior
      recombination deserts characteristic of zebra finch chromosomes. 

PMID- 24863706
TI  - [Cases of poisoning in Germany. Disease entity, documentation, and aspects of the
      event].
AB  - Cases of poisoning account for a distinct share of accidents in Germany, which is
      particularly high for accidents involving children. Cases of poisoning resulting
      from suicidal intent or abuse are not counted as accidents. Compared to other
      cases of disease and accidents, the numerical documentation of cases of poisoning
      is inadequate. Presently, there is no institution in Germany that could make
      available representative and meaningful data on the current state of poisoning.
      Owing to intensive scientific cooperation between the poison information centers
      (funded by the federal states) and the Poison and Product Documentation Center at
      the Federal Institute for Risk Assessment (BfR DocCenter) as well as to
      international cooperation, harmonized and standardized tools have been developed
      for the appropriate documentation and reporting of procedures to account for
      poisoning accidents. The first evaluation for 2005-2012 based on published and
      processed figures for the Federal Republic of Germany yielded the following
      results: Of approximately 230,000 telephone inquiries received in 2012, about
      207,000 involved exposure of humans to different noxae. An annual increase of 3-5
      % was recorded. For 2011, analyses of subsets processed by means of standardized
      methods yielded the following results: Medicines were involved in about 39 % of
      the cases recorded (of these, medicinal products for humans in 99 %);
      chemical/physicochemical agents in about 26 % (of these, cleaning and maintenance
      products in 46 %); products of daily use in about 14 % (of these, cosmetics in 40
      %); and plants in about 10 %. More than 90 % of cases were acute poisoning and
      less than 5 %, chronic poisoning. Regarding the degree of severity of poisoning,
      an asymptomatic course was reported for 44 % of the cases; minor manifestations
      were experienced in 30 %, moderate ones in 6 %, and severe manifestations in 2 %
      of the cases recorded. Fatal cases were rare (< 0.1 %). The majority of cases (67
      %) were caused by poisoning accidents, followed by suicidal action (20 %), with
      abuse and industrial poisoning (4 %) in third position; 1 % of the cases of
      poisoning were attributed to adverse drug reactions (ADR) and mistaking a
      medicinal product for another one. Infants aged 1-2 years have the highest risk
      of poisoning. A panel of the BfR Committee for the Assessment of Poisonings has
      already developed proposals for a national monitoring scheme of poisoning
      incidents. The aim is to prepare annual reports similar to the report of the
      National Poison Data System (NPDS) maintained by the American Association of
      Poison Control Centers (AAPCC) in the USA. 

PMID- 24863707
TI  - [Falls in German hospitals and nursing homes 2006-2013. Frequencies, injuries,
      risk assessment, and preventive measures].
AB  - BACKGROUND: In Germany, a nationwide systematic collection of data regarding fall
      incidents within health-care facilities is lacking. The objective of the study
      was to provide valid and robust data on fall rates, the severity of the fall and
      its resulting injuries, fall risk assessment, and preventive measures offered by
      professional caregivers in German hospitals and nursing homes. MATERIALS AND
      METHODS: Each spring from 2006 to 2013, cross-sectional studies were conducted in
      124 hospitals (n = 22,493 patients) and 332 nursing homes (25,384 residents)
      throughout Germany. Fully trained nurses obtained information on the recent
      history (< 14 days) of the fall and its consequences. Further, they assessed the
      individual fall risk by clinical judgment and recorded ongoing preventive
      measures. RESULTS: The total fall rate was 3.9 % (95 % CI 3.6-4.2) in the
      hospitals and 4.6 % (95 % CI 4.3-4.9) in the nursing homes. Of the fall victims,
      6.4 % of the nursing home residents and 8.8 % of the hospital patients were badly
      injured (i.e., fracture). The fall risk was considered high for residents, with
      two thirds of all residents being affected, while it was lower for the patients,
      at one third. The following factors were associated with fall risk: limited
      mobility, cognitive impairment, recent history of falls for nursing home
      residents, and additionally urinary incontinence and higher age in hospital
      patients. The most common preventive measure was counseling of the individual in
      both settings. CONCLUSION: Although most falls have no severe consequences, the
      study shows that every 20-25th individual has a falling event in hospitals and
      nursing homes within 14 days. Despite the slight variance, the trend of the rates
      remains largely stable. Because specific fall risks were determined, preventive
      measures can be applied in a more personalized manner and care can be improved.
      Finally, the study provides valid and durable figures for national and
      international comparisons.

PMID- 24863708
TI  - [The TraumaRegister DGU(r) as data source for monitoring severe injuries].
AB  - BACKGROUND: The TraumaRegister DGU(r) of the German Society for Trauma Surgery
      (TR-DGU) has collected data on the treatment of severely injured accident victims
      in Germany since 1993. Due to the current number of more than 600 participating
      clinics which regularly receive quality comparison reports, these register data
      are becoming an increasingly more valuable source for healthcare research.
      OBJECTIVES: The aims of this article are to describe the potential of the TR-DGU
      for dealing with epidemiological questions and for describing the quality of the
      process and results for treatment of severely injured patients. MATERIAL AND
      METHODS: The TR-DGU includes approximately 100 details per patient on the person,
      the circumstances of the accident, the injury pattern, the preclinical and
      hospital treatment, the condition of the patient and the outcome. Using
      comparative analyses the observed mortality is adjusted by considering
      prognostically relevant findings. Some key features of the register are reported
      for patients who were treated in German hospitals between 2002 and 2012 with an
      injury severity score (ISS) of  >=9 points. RESULTS: Since 1993 more than 122,000
      patients have been included in the register. The majority are traffic accident
      victims (57 %), followed by patients with falls from low heights (< 3 m, 17 %) or
      greater heights (> 3 m, 16 %). Among the traffic accident victims approximately
      one half are car drivers or passengers (46 %), one quarter are motorbike drivers
      (25 %) and the rest are cyclists (14 %) and pedestrians (13 %). The mortality of
      patients with an ISS 3 9 is 12.8 %. This value is approximately 1-2 % below the
      expected prognosis based on data from the 1990s. DISCUSSION: The TR-DGU is not
      only a successful instrument for external quality assurance of the treatment of
      severely injured patients but also an increasingly more valuable source for
      scientific evaluation within the framework of healthcare research. The
      introduction of regional trauma networks by the DGU has made a substantial
      contribution to the comprehensive compilation of severely injured patients and
      allows increasingly more detailed information on the epidemiology of severe
      injuries in Germany to be compiled.

PMID- 24863709
TI  - [Interventions for mental health sequelae of accidents].
AB  - Emergency psychology and psychotraumatology deal with the psychological sequelae
      of traumatic experiences, i.e., the prevention and early intervention of
      posttraumatic mental health disorders. Accidents are the most prevalent traumatic
      events in the general population that may result in a range of severe trauma and
      adjustment disorders. Accidents happen suddenly, unexpectedly, and can gravely
      threaten health, personal integrity, and life. The prevalence of intermittent and
      chronic psychiatric disorders in the aftermath of severe accidents varies between
      5 and 30 %. Victims suffer from unknown and frightening posttraumatic symptoms,
      often irreversible handicaps as a consequence of their injuries, impairments in
      everyday functioning, and negative impact on the quality of life. The direct and
      indirect burden for society is high. Comprehensive secondary prevention, starting
      with early detection and early intervention of post-accident disorders, is not
      well established in clinical care. In case of severe accidental injuries,
      emergency and medical treatment has absolute priority. But all too often, severe
      mental health problems remain undetected in later treatment phases and therefore
      cannot be addressed adequately. In primary care, knowledge of specific
      psychodiagnostic and treatment options is still insufficient. Prejudices, denial,
      and fear of stigmatization in traumatized victims as well as practical
      constraints (availability, waiting time) in the referral to special evidence
      based interventions limit the access to adequate and effective support. This
      overview presents the objectives, concepts, and therapeutic tools of a stepped
      care model for psychological symptoms after accidental trauma, with reference to
      clinical guidelines. 

PMID- 24863710
TI  - [Injury prevention in young children].
AB  - Epidemiological studies in Germany show that infants and toddlers are at most
      risk of injury and in need of protection. Of all children under the age of 15
      years, they have the highest rates of fatal and severe injuries. Therefore, this
      article aims to show which injury prevention measures have been proven successful
      for this age group. International specialist recommendations are described and
      evidence-based knowledge of interventions is presented from the Cochrane Reviews.
      For the four most frequent child injury mechanisms (drowning, poisoning, burning,
      and falling), the World Health Organization recommends a set of measures covering
      legislation, regulations, changes of environment, education, and emergency
      medical care. Meta-analyses on the effectiveness of interventions related to
      safety at home conclude that informing parents personally (face-to-face) and in
      combination with free safety equipment (e.g., safety gates, smoke alarms)
      increased parents' safety practices significantly. This included advice on not
      using baby walkers. Multifaceted education programs for parents (e.g., visiting
      programs at home or in pediatric clinics) proved to have the highest effect in
      reducing home accidents to children. The prevention of injuries in young children
      should be driven by a multifaceted and data-based approach. Postnatal
      interventions (Fruhe Hilfen) at the community level are especially useful to
      integrate accident prevention at home, because they are connected with family
      visiting programs. 

PMID- 24863712
TI  - [Guide values for 1-butanol in indoor air. Report of the German Ad Hoc Working
      Group on Indoor Guidelines of the Indoor Air Hygiene Committee and of the States'
      Supreme Health Authorities].
AB  - The German Ad Hoc Working Group on Indoor Guidelines of the Indoor Air Hygiene
      Committee and the States' Supreme Health Authorities is issuing indoor air guide
      values to protect public health. No human studies of sufficient quality are
      available for the evaluation of 1-butanol in indoor air. In a well-documented
      oral study on reproduction toxicity in rats, assessed as reliable, impairment of
      embryo development was observed. Benchmark modeling of the study data by US-EPA
      revealed a BMDL10 of 26.1 mg/kg b.w. per day. The working group used this BMDL10
      as the point of departure for the derivation of the guide value II. Considering a
      human respiration rate of 20 m(3) per day and a human body weight of 70 kg, this
      dose was converted into an inhalative concentration. Applying a factor of 0.6 to
      account for the inhalative absorption rate, an allometric extrapolation factor
      from rat to human (factor 4), an interspecies factor of 2.5 for toxicodynamics,
      and a factor of 10 to account for individual differences (intraspecies factor),
      results in a health hazard guide value (RW II) of 2 mg 1-butanol/m(3). The
      benchmark dose calculation of the same study generated a BMDL05 of 12.4 mg/kg
      b.w. per day. Applying the same assessment factors as for RW II, a precautionary
      guide value (RW I) of 0.7 mg 1-butanol/m(3) indoor air is calculated. 

PMID- 24863713
TI  - Epidemiology of bedside stove burns in a retrospective cohort of 5089 pediatric
      patients.
AB  - OBJECTIVE: To retrospectively analyze the epidemiological characteristics of
      pediatric bedside stove burns (PBSB) in China and to explore prevention and
      control measures. METHODS: Data on pediatric burns from three hospitals located
      in the epidemic area were collected from January 1996 to December 2010 and were
      divided into the PBSB group and the control group. The epidemiological
      characteristics and related information for each patient were analyzed. RESULTS:
      A total of 16,595 pediatric burns were found, including 5089 PBSB and 11,506
      other types of burns. The two groups differed significantly in terms of age,
      gender, body parts burned, degree of burn, delay of hospitalization, and
      treatment measures (Ps all<0.05). Risk factors for PBSB included being younger
      than 3 years old, living in a rural area, low literacy level of guardians, not
      receiving health education, and lack of a protective fence protection (Ps
      all<0.05). Furthermore, meal time and winter and spring seasons were high risk
      periods for PBSB. CONCLUSION: The risk factors for PBSB include age, region, time
      of occurrence, and literacy level of guardians. Health education and installation
      of a protective fence between the stove and the bed could reduce the incidence of
      PBSB.

PMID- 24863715
TI  - Not dead yet: the spectre of nursing human resource shortages.

PMID- 24863714
TI  - Value of ultrasonography for diagnosis of synovitis associated with rheumatoid
      arthritis.
AB  - AIM: To investigate the value of ultrasonography (US) for diagnosing synovitis
      associated with rheumatoid arthritis (RA). METHOD: Bilateral metacarpophalangeal
      (MCP), proximal interphalangeal (PIP) II-V and wrist joints of 46 RA patients and
      35 healthy controls were evaluated by quantitative and semiquantitative US.
      Wrists on more severely affected sides of 20 of the 46 patients also underwent
      magnetic resonance imaging (MRI). The MRI and US results were compared. The US
      cutoff to distinguish pathology was calculated. The two US methods were compared
      and the correlation between quantitative methods and clinical serologic markers
      was analyzed. RESULTS: The imaging techniques (US and MRI) for detecting
      synovitis produced consistent results (gamma = 0.70-0.77, P < 0.001). When the
      cutoffs for the MCP and PIP joints were 2.5 and 2.6 mm, respectively; the
      sensitivities/specificities were 82.8%/85.8% and 98.2%/84.8%, respectively. When
      the cutoff for the wrist was 5.2 mm, the sensitivity/specificity was 93.4%/93.4%.
      The average synovial membrane thickness was positively related to biochemical
      markers erythrocyte sedimentation rate, C-reactive protein, anticyclic
      citrullinated peptide antibody, and Disease Activity Index of 28 joints (gamma =
      0.307-0.614; P = 0.020, 0.038, 0.01, < 0.001, respectively) but was poorly
      related to rheumatoid factor immunoglobulin A (RF-IgA), RF-IgM, and RF-IgG (gamma
      = 0.06-0.115; P = 0.45, 0.45, 0.62, respectively). CONCLUSIONS: US is a valid
      method for diagnosing early-stage synovitis, with high-accuracy cutoffs for MCP,
      PIP and wrist joints set at 2.5, 2.6 and 5.2 mm. The mean synovial thicknesses of
      the bilateral wrist, MCP II-IV and PIP II-IV joints can be used to assess disease
      activity.

PMID- 24863716
TI  - Stemming the flow of Canadian nurse migration to the US.
AB  - The migration of nurses from Canada to the United States has occurred for
      decades, although substantial increases have been noted since the 1990s. A survey
      of 4,295 Canadian-educated nurses in the US identified that this trend in
      mobility is largely unchanged. Almost half the nurses in this study migrated to
      the US in search of full-time work, often after unsuccessfully seeking employment
      here in Canada prior to leaving. Incentives to migrate were provided, although
      the opportunity for full-time work was often perceived as an incentive to move.
      While some intent to return is apparent, this is unlikely to occur given the
      levels of satisfaction with work and the high value attributed to Canadian nurses
      by US employers. Policy makers and nurse leaders are urged to use these data to
      formulate strategies aimed at retaining Canada's nurses in this country. 

PMID- 24863717
TI  - The experiences of Canadian-educated early career nurses who practise in the US.
AB  - Nurses who are early in their careers make important decisions that begin them on
      unique career trajectories. One of these decisions may be migration. Little is
      known about the experiences and career decisions made by early career nurses who
      were educated in Canada and are working in the United States. Focus groups were
      conducted with nine nurses to explore and describe their experiences. Utilizing
      the Learning Theory of Career Counselling as a framework, the analysis
      highlighted the environmental conditions and learning experiences described by
      the participants. Two themes were identified: early decisions and ongoing
      decisions. The career trajectories of these nurses were characterized by decision
      making. They made decisions about becoming a nurse, where to work and in what
      clinical specialty. The learning experiences and environments to which they were
      exposed influenced their early decisions and continued to influence their ongoing
      decisions about returning to Canada. 

PMID- 24863718
TI  - I was never recruited: challenges in cross-Canada nurse mobility.
AB  - The internal migration of nurses within Canada has had limited study. This paper
      reports the results of a survey of registered nurses and licensed practical
      nurses who had migrated between the provinces and territories in Canada. Factors
      contributing to internal nurse mobility included seeking full-time work,
      opportunities for career advancement and flexible scheduling options. Few nurses
      received incentives to move between the provinces/territories to work. A number
      of challenges with internal migration are identified, including complexities
      related to licensing and limitations in available job information. Implications
      for nursing health human resources policy related to nurse retention in Canada
      are identified and discussed. 

PMID- 24863719
TI  - Mapping nurse mobility in Canada with GIS: career movements from two Canadian
      provinces.
AB  - Recent years have witnessed the publication of a growing number of studies of
      nursing which, from a disciplinary perspective, are geographical in their
      orientation. Conceptually, while the emphasis in much of this research has been
      focused at the micro scale on the dynamics between nursing and "place," curiously
      there has been scant attention to geometrical "space," and the basic yet
      important locational and distributive features of nursing at the macro scale.
      Noting this gap in the literature, the authors of this paper used a Geographical
      Information System (GIS) to map the movement of 199 nurses from two Canadian
      provinces where they were educated - Manitoba and Newfoundland - to the provinces
      where they currently live and work. While the findings show that nurses who move
      tend to move to nearby provinces, more generally they illustrate the
      effectiveness of GIS for managing data and representing findings from workforce
      studies. 

PMID- 24863720
TI  - Support and access for nursing continuing education in Canadian work
      environments.
AB  - The purpose of this study was to explore how educational opportunities may affect
      nurses' decision to move within Canada. Thematic analysis of qualitative data
      obtained from 35 registered nurses and 35 licensed practical nurses highlighted
      educational opportunities available in Canada and how these influence nurses'
      decision to move across the country for work. The results indicate that Canadian
      nurses value continued learning but face several barriers while trying to further
      their education. Two main themes emerged: support for and access to continuing
      education. Canadian nurses perceive a lack of support, both financially and in
      the form of scheduling, for engaging in continuing education. Additionally, the
      lack of access to accredited continuing education programs was reported. The
      findings and implications of this study are examined within the context of nurse
      mobility. 

PMID- 24863721
TI  - Factors that influence career decisions in Canada's nurses.
AB  - Understanding the experiences of nurses who have moved between the provinces and
      territories (P/T) in Canada for work provides insight into the role of
      professional socialization in career decision-making. This paper analyzes some of
      the qualitative data arising from a survey of nurses from across Canada. The
      findings provide insight into nurses' professional socialization and demonstrate
      that early perceptions and expectations of nursing practice can influence future
      career decisions such as mobility and intent to remain. Participants described
      how "caring" and direct patient contact were central to their choice of nursing
      and career satisfaction. As the data reveal, nursing is also regarded as a career
      that enables mobility to accommodate both family considerations and professional
      development opportunities. The findings highlight the need for professional
      socialization strategies and supports that motivate Canadian nurses to continue
      practising within the profession and the country. 

PMID- 24863722
TI  - LPN perspectives of factors that affect nurse mobility in Canada.
AB  - Although the licensed practical nurse (LPN) workforce represents an ever-growing
      and valuable human resource, very little is known about reasons for practical
      nurse mobility. The purpose of this study was to describe LPN perspectives
      regarding motives for inter-provincial/territorial (P/T) movement in Canada.
      Participants included 200 LPNs from nine P/T, and data were analyzed using a
      qualitative descriptive approach. Three primary themes were identified regarding
      motivators for LPN migration, including (a) scope of practice, (b) education and
      advancement opportunities and (c) professional respect and recognition. Although
      current economic forces have a strong influence on nurse mobility, these findings
      emphasize that there are other equally important factors influencing LPNs to move
      between jurisdictions. As such, policy makers, administrators and researchers
      should further explore and address these themes in order to strengthen Canada's
      nursing workforce. 

PMID- 24863723
TI  - Perspective from the Canadian Nurses Association.

PMID- 24863724
TI  - Global trends, local impact: the new era of skilled worker migration and the
      implications for nursing mobility.
AB  - The global movement towards free trade and market integration has enabled greater
      mobility for skilled professionals, including nurses. As of 2015, newly graduated
      Canadian nurses will enter the register with an exam prepared by the US-based
      National Council of State Boards of Nursing, making Canadian nurses possibly the
      most mobile skilled workers in North America. But given the fragmentation of
      Canada's internal labour market, it is the United States that stands to benefit
      most from greater nurse mobility. 

PMID- 24863725
TI  - Migration and mobility: informing nursing health human resources retention and
      recruitment policy.

PMID- 24863726
TI  - Comparative study of elbow disorders in young high-performance gymnasts.
AB  - The study aimed to investigate the prognosis of osteochondral affection (e.g.,
      osteochondritis dissecans (OCD), cartilage lesions, fractures and bone edema in
      the elbows of high-performance gymnasts (n=30) compared to prognosis results with
      athletes not undergoing excessive stress on the upper extremity (n=29). The study
      also tested a novel isotropic 3D-FSE-sequence (CUBE) technique as an early
      diagnostic modality. Standard protocol was used to conduct the MRI examinations,
      which were then compared to results from the CUBE - sequence. The gymnast group
      (p=0.012) presented a significantly higher prevalence of complaints in the elbow
      joint compared to the other athlete group. Furthermore, osteochondral lesions in
      MRIs appeared more frequently in the group of gymnasts (n=10, 33%, p=0.033),
      including 7 cases (23%) of OCD. In the control athlete group 2 asymptomatic cases
      of OCD and one case of bone edema were detected. The MRI investigation with the
      CUBE - sequence showed similar results as the standard MRI protocol in terms of
      the diagnosis sensitivity. The current study indicates that juvenile gymnasts are
      at a higher risk for osteochondral lesions of the elbow than athletes without
      excessive stress on the upper extremities.

PMID- 24863727
TI  - Contribution of Vertical Strength and Power to Sprint Performance in Young Male
      Athletes.

PMID- 24863728
TI  - Acute effect of ischemic preconditioning is detrimental to anaerobic performance
      in cyclists.
AB  - We verified the acute effect of ischemic preconditioning (IPC) in cyclists before
      high-intensity and short-duration activity. 15 amateur cyclists participated in a
      random crossover model on 2 different days [IPC or CONTROL (CON)]. Ischemic
      preconditioning consisted of 4 cycles of 5 min occlusion/5 min reperfusion in
      each thigh. After IPC or CON, volunteers performed a series of Wingate tests to
      evaluate anaerobic performance (maximal [Pmax] and medium [Pmed] power output,
      total anaerobic power, and fatigue index). Blood lactate concentrations were
      assessed at 6 min after each Wingate test. Ischemic preconditioning decreased
      Pmax (p<0.05), Pmed (p<0.01), and total anaerobic power (p<0.01) in the first
      Wingate, and decreased Pmed (p<0.01) and total anaerobic power (p<0.01) in the
      second Wingate (p<0.01). No significant differences were found in blood lactate
      or fatigue index between IPC and CON. In conclusion, our results indicate that
      IPC has a detrimental acute effect on anaerobic performance in amateur cyclists.
      Compared with positive results of previous studies, the effect of IPC seems to be
      dependent on the type of exercise. 

PMID- 24863729
TI  - Efficacy of face masks and respirators in preventing upper respiratory tract
      bacterial colonization and co-infection in hospital healthcare workers - comment
      on the article by MacIntyre et al.

PMID- 24863730
TI  - Improved photoelectrical properties of MoS(2) films after laser micromachining.
AB  - Direct patterning of ultrathin MoS2 films with well-defined structures and
      controllable thickness is appealing since the properties of MoS2 sheets are
      sensitive to the number of layer and surface properties. In this work, we
      employed a facile, effective, and well-controlled technique to achieve
      micropatterning of MoS2 films with a focused laser beam. We demonstrated that a
      direct focused laser beam irradiation was able to achieve localized modification
      and thinning of as-synthesized MoS2 films. With a scanning laser beam,
      microdomains with well-defined structures and controllable thickness were created
      on the same film. We found that laser modification altered the photoelectrical
      property of the MoS2 films, and subsequently, photodetectors with improved
      performance have been fabricated and demonstrated using laser modified films. 

PMID- 24863731
TI  - Broadband metasurfaces with simultaneous control of phase and amplitude.
AB  - By combining the freedom of both the structural design and the orientation of
      split ring resonator antennas, we demonstrate terahertz metasurfaces that are
      capable of controlling both the phase and amplitude profiles over a very broad
      bandwidth. As an example, we show that the phase-amplitude metasurfaces can be
      engineered to control the diffraction orders arbitrarily. 

PMID- 24863733
TI  - Should antiplatelet medications be held before cervical epidural injections?

PMID- 24863734
TI  - Ancient and recent adaptive evolution in the antiviral TRIM22 gene:
      identification of a single-nucleotide polymorphism that impacts TRIM22 function.
AB  - Tripartite motif protein 22 (TRIM22) is a novel interferon-induced protein that
      potently inhibits the replication of evolutionarily diverse viruses, including
      HIV-1. Altered TRIM22 expression is also associated with diseases, such as
      multiple sclerosis, cancer, and autoimmunity. The factors that influence TRIM22
      expression and antiviral activity are largely unknown. In this study, we adopted
      an evolution-guided functional approach to identify potential genetic
      determinants of TRIM22 function. Evolutionary analysis of TRIM22 from mammals
      spanning >100 million years demonstrated that TRIM22 evolution has been shaped by
      ancient and variable positive selection. We showed that positive selection is
      operating on multiple TRIM22 residues that cluster in putative functional regions
      and that some are predicted to be functionally damaging. Interestingly, the
      second most prevalent TRIM22 SNP in humans (rs1063303) is located at one of these
      positively selected sites. We showed that the frequency of rs1063303:G>C varies
      up to 10-fold between ethnicities and that in some ethnicities SNP rs1063303:G>C
      is being actively maintained in the population. The SNP rs1063303:G>C variant
      also had an inverse functional impact where it increased TRIM22 expression and
      decreased the antiviral activity of TRIM22. Taken together, our data characterize
      the extensive genetic variation in TRIM22 and identify rs1063303:G>C as a highly
      prevalent SNP that influences its function. 

PMID- 24863732
TI  - Maintenance of chromosome structure in Pseudomonas aeruginosa.
AB  - Replication and segregation of genetic information are the activities central to
      the well-being of all living cells. Concerted mechanisms have evolved that ensure
      that each cellular chromosome is replicated once and only once per cell cycle and
      then faithfully segregated into daughter cells. Despite remarkable taxonomic
      diversity, these mechanisms are largely conserved across eubacteria, although
      species-specific distinctions can often be noted. Here, we provide an overview of
      the current state of knowledge about maintenance of the chromosome structure in
      Pseudomonas aeruginosa. We focus on global chromosome organization and its
      dynamics during DNA replication and cell division. Special emphasis is made on
      contrasting these activities in P. aeruginosa and other bacteria. Among unique P.
      aeruginosa, features are the presence of two distinct autonomously replicating
      sequences and multiple condensins, which suggests existence of novel regulatory
      mechanisms. 

PMID- 24863735
TI  - Generation of aminoterminally truncated, stable types of bioactive bovine and
      porcine fibroblast growth factor 4 in Escherichia coli.
AB  - Fibroblast growth factor 4 (FGF4) is a crucial growth factor for the development
      of mammalian embryos. We previously produced hexahistidine-tagged, bovine and
      porcine FGF4 (Pro(32) to Leu(206) ) proteins without a secretory signal peptide
      at the aminoterminus in Escherichia coli. Here, we found that these were
      unstable; site-specific cleavage between Ser(54) and Leu(55) in both FGF4
      derivatives was identified. In order to generate stable FGF4 derivatives and to
      investigate their biological activities, aminoterminally truncated and
      hexahistidine-tagged bovine and porcine FGF4 (Leu(55) to Leu(206) ) proteins,
      termed HisbFGF4L and HispFGF4L, respectively, were produced in E. coli. These
      FGF4 derivatives were sufficiently stable and exerted mitogenic activities in
      fibroblasts. Treatment with the FGF4 derivatives promoted the phosphorylation of
      ERK1/2, which are crucial kinases in the FGF signaling pathway. In the presence
      of PD173074, an FGF receptor inhibitor, the phosphorylation of ERK1/2 was
      inhibited and resulted in abolition of the growth-promoting activity of FGF4
      derivatives. Taken together, we demonstrate that HisbFGF4L and HispFGF4L are
      capable of promoting the proliferation of bovine- and porcine-derived cells,
      respectively, via an authentic FGF signaling pathway. These FGF4 derivatives may
      be applicable for dissecting the roles of FGF4 during embryogenesis in cattle and
      pigs. 

PMID- 24863737
TI  - Identification of urinary miRNA biomarkers for detecting cisplatin-induced
      proximal tubular injury in rats.
AB  - Despite increased focus in recent years on urinary microRNA (miRNA) biomarkers in
      patients with diabetes and chronic kidney diseases, few studies have explored
      urinary miRNA markers in drug-induced nephrotoxicity. Here, we attempted to
      identify urinary miRNA markers suitable for use in detecting cisplatin-induced
      nephrotoxicity in rats. Cisplatin (6mg/kg) was given as a single intraperitoneal
      injection to male Sprague-Dawley (SD) rats, and urine collected from Days 4 to 5
      for 17h under fed or fasted conditions. MiRNAs were identified using TaqMan((r))
      Rodent microRNA PCR cards, and rats were euthanized 5 days after administration.
      Levels of 25 miRNAs were significantly increased in the urine of cisplatin
      treated rats under both fed and fasted conditions, while the levels of these
      miRNAs were decreased in either or both the cortex or outer medulla of the
      kidney. Analysis of time and dose dependency in the urine from rats treated with
      cisplatin (1, 3, and 6mg/kg) on Days 1, 3, and 7, showed levels of 25 miRNAs were
      increased in urine and their appearance correlated with the severity of necrosis
      in the proximal tubules. Four miRNAs (let-7g-5p, miR-93-5p, miR-191a-5p and miR
      192-5p) in urine were measured by absolute quantification, and a strong
      correlation was found between relative and absolute quantification methods. In
      summary, we identified 25 miRNAs in urine that were able to be used as non
      invasive biomarkers for the detection of cisplatin-induced proximal tubular
      injury in rats. This study is the first step in demonstrating the potential
      utility of urinary miRNAs in assessing nephrotoxicity. Further study, such as
      collaborative programs currently underway in the HESI consortium, will clarify
      the usability of identified miRNA markers in measurement of other nephrotoxicants
      and injury-site specificity. 

PMID- 24863736
TI  - Changes in the expression of miRNAs at the pericentral and periportal regions of
      the rat liver in response to hepatocellular injury: comparison with the changes
      in the expression of plasma miRNAs.
AB  - MicroRNAs (miRNAs) in body fluids have received attention as potential biomarkers
      of organ damage because miRNAs that are highly or specifically expressed in a
      given organ are likely released into body fluids as a result of damage to that
      organ. We previously determined that the plasma miRNA profile in rats was
      dramatically changed due to acetaminophen (APAP)-induced pericentral necrosis and
      methapyrilene (MP)-induced periportal necrosis in the liver. The purpose of this
      study was to examine whether the expression of hepatic miRNAs is differentially
      modulated at different zones due to injury and to examine the relationship of the
      hepatic miRNA profile with the changes in the plasma miRNA expression profile.
      Through the laser microdissection of the periportal and periportal regions of the
      liver and TaqMan microRNA Array analysis, we found that 49 miRNAs are
      differentially expressed between the pericentral and periportal regions of
      control rats. In both APAP- and MP-treated rats, the miRNAs that presented
      decreased expression dominated in both the injured and non-injured areas compared
      with the miRNAs that exhibited increased expression. The changes in miRNA
      expression in each region of the liver were compared with those observed in the
      plasma. Of the 301 plasma miRNAs with expression that was changed as a result of
      APAP administration, only 21% were changed in the injured area of the liver. Of
      the 263 plasma miRNAs with expression that was changed due to MP administration,
      only 24% were changed in the injured area of the liver. Thus, the miRNA
      expression profiles in the plasma do not merely reflect the release of miRNAs
      from the damaged cells in the liver. This report provides the first demonstration
      of zonal miRNA expression in the liver and of the relationship of the miRNA
      expression profile in a tissue with the plasma miRNA profile. 

PMID- 24863738
TI  - Use of in vitro data in developing a physiologically based pharmacokinetic model:
      Carbaryl as a case study.
AB  - In vitro-derived information has been increasingly used to support and improve
      human health risk assessment for exposure to chemicals. Physiologically based
      pharmacokinetic (PBPK) modeling is a key component in the movement toward in
      vitro-based risk assessment, providing a tool to integrate diverse experimental
      data and mechanistic information to relate in vitro effective concentrations to
      equivalent human exposures. One of the challenges, however, in the use of PBPK
      models for this purpose has been the need for extensive chemical-specific
      parameters. With the remarkable advances in in vitro methodologies in recent
      years, in vitro-derived parameters can now be easily incorporated into PBPK
      models. In this study we demonstrate an in vitro data based parameterization
      approach to develop a physiologically based pharmacokinetic and pharmacodynamic
      (PBPK/PD) model, using carbaryl as a case study. In vitro experiments were
      performed to provide the chemical-specific pharmacokinetic (PK) and
      pharmacodynamic (PD) parameters for carbaryl in the PBPK model for this compound.
      Metabolic clearance and cholinesterase (ChE) interaction parameters for carbaryl
      were measured in rat and human tissues. These in vitro PK and PD data were
      extrapolated to parameters in the whole body PBPK model using biologically
      appropriate scaling. The PBPK model was then used to predict the kinetics and ChE
      inhibition dynamics of carbaryl in vivo. This case study with carbaryl provides a
      reasonably successful example of utilizing the in vitro to in vivo extrapolation
      (IVIVE) approach for PBPK model development. This approach can be applied to
      other carbamates with an anticholinesterase mode of action as well as to
      environmental chemicals in general with further refinement of the current
      shortcomings in the approach. It will contribute to minimizing the need for in
      vivo human data for PBPK model parameterization and evaluation in human risk
      assessments. 

PMID- 24863739
TI  - Changes in the prescription pattern of antipsychotics for schizophrenic
      outpatients after the implementation of a global budgeting program.
AB  - BACKGROUND: A hospital-based global budget (GB) program was implemented by the
      Taiwan Bureau of National Health Insurance (TBNHI) to control the rising costs of
      medical care. We investigated whether the introduction of the GB program affected
      prescriptions for second-generation antipsychotics (SGAs) for schizophrenic
      outpatients in public and private medical and psychiatric centers. METHODS: The
      prescription data of schizophrenic outpatients treated between 2001 and 2004 were
      retrieved from the TBNHI database, which included outpatients who were diagnosed
      as having schizophrenia during the period from 1996 to 2001. Because the new
      health insurance policy may have had a lag effect on physicians' decision
      regarding SGA prescription, we used January 2004 as the timepoint to divide the
      data, which was 6 months after GB implementation. Thus, data from the 6-month
      period immediately after the GB implementation were included in the pre-GB
      period. Second-generation antipsychotics included in the study were clozapine,
      risperidone, olanzapine, quetiapine, ziprasidone, zotepin, and amisulpride.
      RESULTS: After January 2004, the proportion of SGA use in outpatient departments
      did not show an upward trend, as had been observed in the pre-GB period, which
      appeared at a staggering pace lasting for 12 months (p = 0.0004). Compared with
      medical centers, SGA expenditures in the psychiatric centers were less affected
      in the GB period (p < 0.0001). Compared to the private sector, the SGA
      expenditures in the public sector were less affected in the GB period (p <
      0.019). CONCLUSION: We concluded that the GB implementation reduced SGA
      expenditures significantly. The extent of influence varied among hospitals (i.e.,
      public versus private, medical versus psychiatric centers), which was most likely
      caused by financial factors.

PMID- 24863740
TI  - The characterization of the fat bodies and oenocytes in the adult females of the
      sand fly vectors Lutzomyia longipalpis and Phlebotomus papatasi.
AB  - The fat body (FB) is responsible for the storage and synthesis of the majority of
      proteins and metabolites secreted into the hemolymph. Oenocytes are responsible
      for lipid processing and detoxification. The FB is distributed throughout the
      insect body cavity and organized as peripheral and perivisceral portions in the
      abdomen, with trophocytes and oenocytes attached to the peripheral portion. Here,
      we investigated the morphology and the subcellular changes in the peripheral and
      perivisceral FBs and in oenocytes of the sand flies Lutzomyia longipalpis and
      Phlebotomus papatasi after blood feeding. In L. longipalpis two-sized oenocytes
      (small and large) were identified, with both cell types displaying well-developed
      reticular system and smooth endoplasmic reticulum, whereas in P. papatasi, only
      small cells were observed. Detailed features of FBs of L. longipalpis and P.
      papatasi are shared either prior to or after blood feeding. The peripheral and
      perivisceral FBs responded to blood feeding with the development of glycogen
      zones and rough endoplasmic reticulum. This study provides the first detailed
      description of the FBs and oenocytes in sand flies, contributing significantly
      towards are better understanding of the biology of such important disease
      vectors.

PMID- 24863742
TI  - The Korea regional issue of Mass Spectrometry Reviews.

PMID- 24863744
TI  - DDD-028: a potent potential non-opioid, non-cannabinoid analgesic for neuropathic
      and inflammatory pain.
AB  - DDD-028 (4), a novel pentacyclic pyridoindolobenzazepine derivative was evaluated
      in vitro for receptor binding affinity and in vivo for analgesic activity using
      rodent models of neuropathic and inflammatory pain. DDD-028 does not bind to
      opioid, cannabinoid, dopamine, or histamine receptors. DDD-028 is very active
      even at the low oral dose of 1-5 mg/kg in both neuropathic, (spinal nerve
      ligation and chronic constriction injury) and inflammatory (Complete Freund's
      Adjuvant Induced) models of pain. DDD-028 appears to be about 6-fold more potent
      than pregabalin and indomethacin. Visual observation of all the animals used in
      these studies indicated that DDD-028 is well tolerated without any sedation.
      Thus, DDD-028 seems to be a promising candidate for the treatment of neuropathic
      and inflammatory pain without the possible side effects or abuse potential
      associated with opioid or cannabinoid activities.

PMID- 24863743
TI  - Neuregulin1-beta decreases IL-1beta-induced neutrophil adhesion to human brain
      microvascular endothelial cells.
AB  - Neuroinflammation contributes to the pathophysiology of diverse diseases
      including stroke, traumatic brain injury, Alzheimer's disease, Parkinson's
      disease, and multiple sclerosis, resulting in neurodegeneration and loss of
      neurological function. The response of the microvascular endothelium often
      contributes to neuroinflammation. One such response is the upregulation of
      endothelial adhesion molecules which facilitate neutrophil adhesion to the
      endothelium and their migration from blood to tissue. Neuregulin-1 (NRG1) is an
      endogenous growth factor which has been reported to have anti-inflammatory
      effects in experimental stroke models. We hypothesized that NRG1 would decrease
      the endothelial response to inflammation and result in a decrease in neutrophil
      adhesion to endothelial cells. We tested this hypothesis in an in vitro model of
      cytokine-induced endothelial injury, in which human brain microvascular
      endothelial cells (BMECs) were treated with IL-1beta, along with co-incubation
      with vehicle or NRG1-beta. Outcome measures included protein levels of
      endothelial ICAM-1, VCAM-1, and E-selectin, as well as the number of neutrophils
      that adhere to the endothelial monolayer. Our data show that NRG1-beta decreased
      the levels of VCAM-1, E-selectin, and neutrophil adhesion to brain microvascular
      endothelial cells activated by IL1-beta. These findings open new possibilities
      for investigating NRG1 in neuroprotective strategies in brain injury. 

PMID- 24863745
TI  - Synthesis, structure-activity relationships and biological evaluation of
      barbigerone analogues as anti-proliferative and anti-angiogenesis agents.
AB  - A series of barbigerone analogues (7a-7w, 13a-13x) were designed, synthesized and
      biologically evaluated for their anti-proliferative and anti-angiogenic
      activities. Among these compounds, compound 13a exhibited the most potent
      inhibitory effect on the proliferation of HUVECs, HepG2, A375, U251, B16, and
      HCT116 cells (IC50=3.80, 0.28, 1.58, 3.50, 1.09 and 0.68 MUM, respectively).
      Compound 13a inhibited the angiogenesis in zebrafish embryo assay in a
      concentration-dependent manner. Furthermore, 13a also effectively inhibited the
      migration and capillary like tube formation of human umbilical vein endothelial
      cell in vitro. These results support the further investigation of this class of
      compounds as potential anti-proliferative and anti-angiogenesis agents.

PMID- 24863746
TI  - Socioecological perspectives on cervical cancer and cervical cancer screening
      among Asian American women.
AB  - Although cervical cancer is one of the most commonly diagnosed cancers among
      Vietnamese American women (VAW) and Korean American women (KAW), both groups
      consistently report much lower rates of cervical cancer screening compared with
      other Asian ethnic subgroups and non-Hispanic Whites. This study aimed to explore
      multilevel factors that may underlie low screening rates among VAW and KAW living
      in a city where their ethnic communities are relatively small. The
      socioecological model was used as a conceptual framework. Thirty participants
      were conveniently recruited from ethnic beauty salons run by VA and KA
      cosmetologists in Albuquerque, New Mexico. The participants' average age was 44.6
      years (SD = .50; range = 21-60). Most participants were married (80 %) and
      employed (73.3 %), and had health insurance (83.3 %). A qualitative interview was
      conducted in Vietnamese or Korean and transcribed verbatim. A thematic content
      analysis was used to identify major codes, categories, and patterns across the
      transcripts. The study identified several factors at the individual (e.g.,
      pregnancy, poverty, personality), interpersonal (e.g., family responsibility,
      mother as influential referent), and community (e.g., lack of availability,
      community size) levels. The study sheds light on four major areas that must be
      taken into consideration in the development of culturally appropriate, community
      based interventions aimed to reduce disparities in cervical cancer screening
      among ethnic minority women in the United States: (1) ethnic community size and
      geographic location; (2) cross-cultural similarities and dissimilarities; (3)
      targeting of not only unmarried young women, but also close referents; and (4)
      utilization of trusted resources within social networks.

PMID- 24863747
TI  - Gender differences in the impact of poverty on health: disparities in risk of
      diabetes-related amputation.
AB  - AIMS: To assess the combined impact of socio-economic status and gender on the
      risk of diabetes-related lower extremity amputation within a universal healthcare
      system. METHODS: We conducted a population-based cohort study using
      administrative health databases from Ontario, Canada. Adults with pre-existing or
      newly diagnosed diabetes (N = 606 494) were included and the incidence of lower
      extremity amputation was assessed for the period 1 April 2002 to 31 March 2009.
      Socio-economic status was based on neighbourhood-level income groups, assigned to
      individuals using the Canadian Census and their postal code of residence.
      RESULTS: Low socio-economic status was associated with a significantly higher
      incidence of lower extremity amputation (27.0 vs 19.3 per 10,000 person-years in
      the lowest (Q1) vs the highest (Q5) socio-economic status quintile. This
      relationship persisted after adjusting for primary care use, region of residence
      and comorbidity, and was greater among men (adjusted Q1:Q5 hazard ratio 1.41, 95%
      CI 1.30-1.54; P < 0.0001 for all male gender-socio-economic status interactions)
      than women (hazard ratio 1.20, 95% CI 1.06-1.36). Overall, the incidence of lower
      extremity amputation was higher among men than women (hazard ratio for men vs
      women: 1.87, 95% CI 1.79-1.96), with the greatest disparity between men in the
      lowest socio-economic status category and women in the highest (hazard ratio
      2.39, 95% CI 2.06-2.77 and hazard ratio 2.30, 95% CI 1.97-2.68, for major and
      minor amputation, respectively). CONCLUSIONS: Despite universal access to
      hospital and physician care, we found marked socio-economic status and gender
      disparities in the risk of lower extremity amputation among patients with
      diabetes. Men living in low-income neighbourhoods were at greatest risk.

PMID- 24863749
TI  - Trends in prevalence from 1990 to 2007 of patients hospitalized with heart
      failure in Sweden.
AB  - AIMS: To investigate trends in absolute numbers and prevalence from 1990 to 2007
      of patients hospitalized with heart failure (HF) in Sweden. METHODS AND RESULTS:
      National inpatient and cause-specific death registers were used to calculate age-
      and sex-specific trends in absolute numbers and prevalence from 1990 to 2007 of
      patients hospitalized with HF in Sweden. Absolute numbers increased from 105 449
      in 1990 to 144 925 in 2007, with a 77% increase in patients aged 85-99 years. The
      overall age-adjusted prevalence in 1990 was 1.73%, and this increased with an
      estimated annual percentage change (EAPC) of 4.3% [95% confidence interval (CI)
      3.6-4.9%] from 1990 to 1995, with no further significant change until 2002. The
      single year with the highest prevalence was 1998, when it peaked at 2.13%. The
      prevalence then declined slowly from 2002 (EAPC -1.1, 95% CI -1.5% to -0.6%) to
      1.99% in 2007. The decrease in prevalence was not found in persons <65 years,
      where, instead, an increase was found throughout the period. CONCLUSION: Fears of
      an impending HF 'epidemic' could not be confirmed in this analysis of trends in
      prevalence for the period 1990-2007 of patients hospitalized with HF in Sweden.
      An overall slight decrease in age-adjusted prevalence was observed from 2002. The
      prevalence in patients <65 years increased markedly. In absolute numbers, there
      was a substantial increase among the very old, consistent with demographic
      changes.

PMID- 24863748
TI  - Combined effects of bisphenol A and cadmium on growth and nitrate assimilation of
      soybean seedling roots.
AB  - Bisphenol A (BPA) and cadmium (Cd) pollution exist simultaneously in many
      regions. However, little information is available regarding the combined effects
      of BPA and Cd pollution on plants. Plant roots are in direct contact with the
      soil, which is an important compartment of BPA and Cd. In the present study, the
      effects of combined BPA and Cd pollution on soybean seedling roots were evaluated
      in pot experiments. Combined treatment with BPA and Cd at low concentrations (1.5
      mg/kg BPA and 0.2 mg/kg Cd) improved soybean seedling root growth. However, other
      combined BPA and Cd treatments, including combined treatment with BPA (Cd) at the
      low concentration and Cd (BPA) at the high concentration as well as combined
      treatment with BPA and Cd at the high concentration, inhibited soybean seedling
      root growth. The improvement or inhibition of soybean seedling root growth was
      greater in the combined BPA and Cd treatments than in single treatments. The
      effects of the combined BPA and Cd treatments on root growth resulted from
      changes in nitrate assimilation. In addition, the combined effects of BPA and Cd
      on the nitrate and ammonium contents in roots are discussed. The present research
      provides a basic understanding of the combined effects of BPA and Cd pollution on
      plant roots.

PMID- 24863750
TI  - Metastatic breast cancer in young women: a population-based cohort study to
      describe risk and prognosis.
AB  - BACKGROUND: There is limited information on the risk of metastatic breast cancer
      (MBC) to inform younger women, particularly those under 40 years. AIMS: We
      conducted a retrospective analysis of a population-based cohort study to describe
      the risk, site and prognosis of MBC in young women under 40 years with an initial
      diagnosis of non-metastatic breast cancer and compared with older women. METHODS:
      Data were extracted from the New South Wales Central Cancer Registry and the
      Admitted Patient Data Collection database between 2001-2007. Main outcome
      measures were 5-year cumulative incidence of MBC, prognostic factors for MBC and
      overall survival (OS) from the date of MBC diagnosis. RESULTS: Three hundred and
      ninety-five (6%) of 6640 women with non-metastatic BC were <40 years. The 5-year
      cumulative incidence of MBC was 24% (95% CI 20-29%) for women <40 years with non
      metastatic BC, compared with 9% (95% CI 9-10%) for women >=40 years. Significant
      independent risk factors for MBC <= 5 years were age <40, regional disease at
      diagnosis, low socioeconomic status and the presence of other non-breast primary.
      At first record of MBC, visceral sites were more common for women <40 years than
      >=40 (54% vs 43%; P = 0.03). Median survival for women with MBC within 5 years
      was not significantly different between young and older women (<40 years 18
      months vs >=40 years 14 months; log-rank P = 0.21). CONCLUSIONS: Women with non
      metastatic BC before age 40 have a higher 5-year risk of developing MBC than
      older women. There were no significant differences in median survival following
      MBC between young and older women.

PMID- 24863751
TI  - Low-grade dietary-related inflammation and survival after colorectal cancer
      surgery.
AB  - PURPOSE: Prolong inflammation is a central process observed in several chronic
      conditions and may be responsible for survival. There is an increasing evidence
      showing the role of diet in inflammation and habitual diet may be responsible for
      low-grade inflammation. The purpose of our study was to assess the effect of
      inflammatory properties of habitual diet measured by the Dietary Inflammatory
      Index (DII) on survival among surgical patients treated for colorectal cancer
      (CRC). METHODS: A follow-up study among 689 CRC patients (mean age 58 years, +/
      8.9; 56.7 % males) treated surgically was performed in Krakow, Poland. Habitual
      diet was assessed by a standardized semiquantitative food frequency
      questionnaire. Next, 23 dietary items were used to calculate DIIs. Vital records
      were verified to determine status of the participants. RESULTS: Study has shown
      linear association between DII and survival time among CRC patients with totally
      removed cancer treated by chemotherapy (b = -0.13, p = 0.024). After adjustment
      for several important covariates, DII was associated with survival during up to 3
      years after surgery, but only in patients without distant metastases (3-year
      HRDII>-2.27 = 0.61, 95 % CI 0.38-0.99). CONCLUSIONS: The results of the
      investigation have shown the usefulness of the DII as a potential predictor of
      survival among patients without distant metastases treated surgically for CRC.

PMID- 24863752
TI  - Photosensitizing effectiveness of a novel chlorin-based photosensitizer for
      photodynamic therapy in vitro and in vivo.
AB  - PURPOSE: Photodynamic therapy (PDT) is a promising noninvasive treatment, which
      has been approved by the US Food and Drug Administration for the treatment of
      localized tumors. With the aim to select an appropriate photosensitizer for tumor
      treatment in PDT, the antitumor effect of a novel chlorin-based photosensitizer,
      meso-tetra (3-morphlinomethyl-4-methoxyphenyl) chlorin (TMMC) (Fig. 1a) on two
      types of human malignant tumor cells in vitro and a esophageal cancer model in
      nude mice, was evaluated in the present paper. Fig. 1 Chemical structure and
      spectrum properties of TMMC in DMF. a Chemical structure of TMMC in DMF. b UV-Vis
      absorption spectrum of TMMC in DMF. Its maximum absorbance is at 423 nm, and at
      527, 555, 600, 655 nm and 712 nm, also it has absorption. c Emission spectrum of
      TMMC, which was excited at 514 nm, and its peaks were at 656 and 720 nm. d The
      matrix of excitation and emission spectra (Ex: 300-550 nm, Em: 600-780 nm)
      METHODS: The efficiency of TMMC-PDT in vitro was analyzed by MTT assay and
      clonogenic assay. The intracellular distribution of photosensitizers was detected
      with laser scanning confocal microscopy. The accumulation of TMMC in human
      malignant tumor cells was measured by Fluorescence Spectrometer, and the pathway
      of cell death was analyzed by flow cytometry. Eca-109 tumor model was used to
      evaluate the antitumor effects of TMMC-mediated PDT. And the singlet oxygen
      quantum yield of TMMC was also measured using DPBF as substrate. RESULTS: TMMC
      shows a singlet oxygen quantum yield of 0.59 and displays a characteristic long
      wavelength absorption peak at 655 nm. The accumulation of TMMC increased in time
      dependent manner, and it was found in cytoplasm and nuclear membranes. TMMC-PDT
      induced cell death by the major death pathway of necrosis and significantly
      reduced the growth of Eca-109 tumors in nude mice (180 mW/cm(2), 120 J/cm(2)).
      CONCLUSION: The studies suggest that TMMC is an effective photosensitizer for PDT
      to tumors. Therefore, TMMC has great potentials for tumor treatment in PDT and
      deserves further investigation.

PMID- 24863753
TI  - Current and newer agents for hypertensive emergencies.
AB  - Hypertension is an increasingly prevalent chronic illness. The condition may
      present as a hypertensive crisis, and this entity may be further categorized as
      either hypertensive emergency or urgency. As the presentation is quite variable
      and is dependent upon the specific end-organ injury, a thorough history and
      examination are necessary. Once the underlying pathology is known, a target blood
      pressure can be determined and a specific therapeutic agent selected. The choice
      of most appropriate agent must take into consideration coexisting morbidities,
      desired rate of blood pressure decline, monitoring capabilities of the
      environment, and experience of the clinician. In hypertensive emergencies, the
      therapeutic goal is to protect remaining end-organ function, reduce the risk of
      complications, and thereby improve patient outcomes. This article reviews
      commonly used antihypertensive medications as well as evidence-based
      recommendations for state-of-the-art treatment for hypertensive emergencies.

PMID- 24863754
TI  - Structural and biochemical characterization of the folyl-poly-gamma-l-glutamate
      hydrolyzing activity of human glutamate carboxypeptidase II.
AB  - In addition to its well-characterized role in the central nervous system, human
      glutamate carboxypeptidase II (GCPII; Uniprot ID Q04609) acts as a folate
      hydrolase in the small intestine, participating in the absorption of dietary
      polyglutamylated folates (folyl-n-gamma-l-glutamic acid), which are the
      provitamin form of folic acid (also known as vitamin B9 ). Despite the role of
      GCPII as a folate hydrolase, nothing is known about the processing of
      polyglutamylated folates by GCPII at the structural or enzymological level.
      Moreover, many epidemiologic studies on the relationship of the naturally
      occurring His475Tyr polymorphism to folic acid status suggest that this
      polymorphism may be associated with several pathologies linked to impaired folate
      metabolism. In the present study, we report: (a) a series X-ray structures of
      complexes between a catalytically inactive GCPII mutant (Glu424Ala) and a panel
      of naturally occurring polyglutamylated folates; (b) the X-ray structure of the
      His475Tyr variant at a resolution of 1.83 A; (c) the study of the recently
      identified arene-binding site of GCPII through mutagenesis (Arg463Leu, Arg511Leu
      and Trp541Ala), inhibitor binding and enzyme kinetics with polyglutamylated
      folates as substrates; and (d) a comparison of the thermal stabilities and folate
      hydrolyzing activities of GCPII wild-type and His475Tyr variants. As a result,
      the crystallographic data reveal considerable details about the binding mode of
      polyglutamylated folates to GCPII, especially the engagement of the arene binding
      site in recognizing the folic acid moiety. Additionally, the combined structural
      and kinetic data suggest that GCPII wild-type and His475Tyr variant are
      functionally identical.

PMID- 24863756
TI  - Thermodynamic impact of abasic sites on simulated translesion DNA synthesis.
AB  - Loss of a base in DNA and the creation of an abasic (apurinic/apyrimidinic, AP)
      site is a frequent lesion that may occur spontaneously, or as a consequence of
      the action of DNA-damaging agents. The AP lesion is mutagenic or lethal if not
      repaired. We report a systematic thermodynamic investigation by differential
      scanning calorimetry on the evolution, during primer extension, of a model AP
      site in chemically simulated DNA translesion synthesis. Incorporation of dAMP
      (deoxyadenosine monophosphate), as well as dTMP (deoxythymidine monophosphate),
      opposite an AP site is enthalpically unfavorable, although incorporation of dTMP
      is more enthalpically unfavorable than that of dAMP. This finding is in a good
      agreement with experimental data showing that AP sites block various DNA
      polymerases of eukaryotic and prokaryotic origin and that, if bypassed, dAMP is
      preferentially inserted, whereas insertion of dTMP is less likely. The results
      emphasize the importance of thermodynamic contributions to the insertion of
      nucleotides opposite an AP site by DNA polymerases. 

PMID- 24863755
TI  - Associations between serum concentrations of perfluoroalkyl acids and serum lipid
      levels in a Chinese population.
AB  - Perfluoroalkyl acids (PFAAs) have been used in a variety of products for many
      years and have been detected worldwide in human serum. Previous studies have
      suggested the potential effects of PFAAs on serum lipids. To investigate the
      associations between serum concentrations of PFAAs and serum lipid levels, 133
      participants were randomly selected from the people coming for health check-up in
      Yuanyang Red Cross Hospital of Henan, China. Linear regression analysis revealed
      that perfluoro-octanoic acid (PFOA), perfluorononanoic acid (PFNA), and
      perfluorodecanoic acid (PFDA), with a median concentration of 1.43, 0.37, and
      0.19 ng/mL, respectively, were positively associated with total cholesterol (TC).
      Those in the highest quartile of PFOA exposure had ln-TC levels 0.24 mmol/L
      higher than those in the lowest quartile. For PFNA and PFDA, effect estimates
      were 0.25 and 0.16 mmol/L, respectively. A positive association between high
      density lipoprotein cholesterol (HDLC) and PFDA was found, and there was a 0.18
      mmol/L increase of HDLC for the top PFDA quartile compared with the lowest
      quartile. PFOA and PFNA were positively associated with low-density lipoprotein
      cholesterol (LDLC). Ln-LDLC levels of people in both top PFOA and PFNA quartiles
      were 0.33 mmol/L higher than those in the lowest quartiles. Logistic regression
      analysis indicated that increased PFOA and PFOS quartiles were positively
      associated with an increased risk of abnormal TC and LDLC when controlling for no
      confounding factors.

PMID- 24863757
TI  - Patient experiences with gene panels based on exome sequencing in clinical
      diagnostics: high acceptance and low distress.
AB  - The Radboud University Medical Center was among the first to implement two-step
      exome sequencing in clinical genetic diagnostics. This study is the first to
      evaluate patient experiences with gene panels based on exome sequencing, using
      quantified psychological variables: acceptance, psychological distress,
      expectations of heredity and unsolicited findings. Between August 2011 and July
      2012, 177 patients diagnosed with early-onset colorectal/kidney cancer, deafness,
      blindness or movement disorder consented to diagnostic exome sequencing offered
      by clinical geneticists. Baseline questionnaires were sent to 141 adults,
      returned by 111 with median age of 49 [22-79] years and positive family history
      in 81%. Follow-up included 91 responders at median 4 [2-22] weeks after results
      from known gene panels per diagnosis group; exome-wide analysis is ongoing.
      Confirmed or possibly pathogenic mutations were found in 31% with one unsolicited
      finding (oncogenetic panel). Most patients (92%) were satisfied. There were no
      significant changes in heredity-specific distress (18% at baseline, 17% at follow
      up) and expectations of heredity. Fewer patients expected unsolicited findings at
      follow-up (29% vs 18%, p = 0.01). Satisfaction and distress were equal in those
      with vs without mutations. In conclusion, most adults accepted and were satisfied
      with gene panels based on diagnostic exome sequencing, few reporting distress. 

PMID- 24863758
TI  - Large-scale preparation of indium-based infinite coordination polymer
      hierarchical nanostructures and their good capability for water treatment.
AB  - The removal of dyes in wastewater has been of much interest in the recent decades
      because dyes are stable, toxic and even potentially carcinogenic, and their
      release into environment causes serious environmental, aesthetical, and health
      problems. In the current work, indium-based coordination polymer particles (In
      CPPs) have been fabricated via a facile solvothermal synthesis without any
      template or surfactant. In-CPPs are composed of hierarchical nanostructures
      assembled from abundant nanoplates with thickness of about 20 nm. Owing to their
      high BET surface area and pore volume, In-CPPs exhibit excellent adsorption
      capability for Congo red with a maximum capacity of 577 mg g(-1), which was
      higher than that of most materials reported to now. In-CPPS can also be
      outstanding adsorbents for removing other dyes such as acid chrome blue K,
      brilliant red GR and brilliant green. Furthermore, after calcinations in air In
      CPPs can be converted to morphology-preserved porous In2O3 products which can
      detect NOx gas in air at room temperature.

PMID- 24863759
TI  - Factors controlling the formation and stability of foams used as precursors of
      porous materials.
AB  - The remarkable stability of particle-stabilized foams and the opportunity to use
      them for production of novel porous materials have been attracting the
      researchers' attention in the recent years. The major aim of the current study is
      to clarify the factors, controlling the foamability and stability of foams,
      formed from concentrated silica suspensions in the presence of the amphoteric
      surfactant CAPB. The experiments showed that: (1) two regions can be defined with
      respect to suspension foaminess: Region 1 - good foaming and Region 2 - strongly
      suppressed foaming. The foam volume decreased linearly with the increase of
      suspension viscosity, so that Region 2 appears as a result of the excessively
      high suspension viscosity. (2) Based on foam stability four sub-regions were
      observed in Region 1: region 1S - stable foams, which can be dried to form stable
      porous materials; 1UD - foams which are unstable with respect to water drainage
      and collapse upon drying; 1UC - foams which are stable to drainage, but are
      unstable to drying, due to crack formation; 1UF - unstable foams which completely
      fall apart upon drying. (3) Foams in Regions 1S and 1UC had yield stress above 10
      Pa which prevented liquid drainage, while foams from Region 1UD drained because
      of their lower yield stress. (4) The particles in the foams assembled in a 3D
      network in the Plateau channels and the nodes, while surfactant stabilized the
      foam films between the bubbles. These results define the conditions, appropriate
      for formation of stable, highly porous silica materials with low mass density,
      which can be further modified (sintered, impregnated, hydrophobized, etc.) to
      serve as catalyst supports, porous filters, insulating materials, etc.

PMID- 24863760
TI  - Surfactant softening of plant leaf cuticle model wax--a Differential Scanning
      Calorimetry (DSC) and Quartz Crystal Microbalance with Dissipation (QCM-D) study.
AB  - The aim was to quantify the softening effect that two surfactants (C10EO7 and
      C8G1.6) have on a plant leaf cuticle model wax. Effects on the thermotropic phase
      behavior and fluidity of the wax (C22H45OH/C32H66/H2O) were determined. The model
      wax is crystalline at ambient conditions, yet it is clearly softened by the
      surfactants. Both surfactants decreased the transition temperatures in the wax
      and the G"/G' ratio of the wax film increased in irreversible steps following
      surfactant exposure. C10EO7 has a stronger fluidizing effect than C8G1.6 due to
      stronger interaction with the hydrophobic waxes. Intracuticular waxes (IW)
      comprise both crystalline and amorphous domains and it has previously been
      proposed that the fluidizing effects of surfactants are due to interactions with
      the amorphous parts. New data suggests that this may be a simplification.
      Surfactants may also absorb in crevices between crystalline domains. This causes
      an irreversible effect and a softer cuticle wax. 

PMID- 24863762
TI  - A facile fabrication of amphiphilic Janus and hollow latex particles by
      controlling multistage emulsion polymerization.
AB  - In this paper, we found that morphology controllable compound latex particles
      could be prepared by controlling the multistage emulsion polymerization.
      Influences of the content of methacrylic acid (MAA) on preparing the hydrophilic
      cores and the particles were investigated with the observation of dynamic light
      scattering (DLS) and transmission electron microscope (TEM) results. The acorn
      like latex particles were synthesized by partially encapsulated with hydrophobic
      polystyrene (PSt)-layer. With adding moderate polarity polymethylmethacrylate
      (PMMA) interlayer, the hydrophilic cores could be fully encapsulated by the
      hydrophobic PSt-layer, and the core-shell structure formed. After alkali
      treatment, the acorn-like and core-shell latex particles evolved into amphiphilic
      Janus and hollow latex particles, respectively. The morphology of latex particles
      was investigated by TEM, and the forming mechanism of amphiphilic Janus and
      hollow latex particles was proposed. 

PMID- 24863763
TI  - Removal of methyl orange from aqueous solutions through adsorption by calcium
      aluminate hydrates.
AB  - Methyl orange (MO) is a kind of anionic dye and widely used in industry. In this
      study, tricalcium aluminate hydrates (Ca-Al-LDHs) are used as an adsorbent to
      remove methyl orange (MO) from aqueous solutions. The resulting products were
      studied by X-ray diffraction (XRD), infrared spectroscopy (MIR), thermal analysis
      (TG-DTA) and scanning electron microscope (SEM). The XRD results indicated that
      the MO molecules were successfully intercalated into the tricalcium aluminate
      hydrates, with the basal spacing of Ca-Al-LDH expanding to 2.48 nm. The MIR
      spectrum for CaAl-MO-LDH shows obvious bands assigned to the N=N, N=H stretching
      vibrations and S=O, SO3(-) group respectively, which are considered as marks to
      assess MO(-) ion intercalation into the interlayers of LDH. The overall
      morphology of CaAl-MO-LDH displayed a "honey-comb" like structure, with the
      adjacent layers expanded.

PMID- 24863761
TI  - Gold nanoparticles decorated with oligo(ethylene glycol) thiols: surface charges
      and interactions with proteins in solution.
AB  - We have studied oligo(ethylene glycol) (OEG) thiol self-assembled monolayer (SAM)
      coated gold nanoparticles (AuOEG) and their interactions with proteins in
      solutions using electrophoretic and dynamic light scattering (ELS and DLS). The
      results are compared with poly(ethylene glycol) (PEG) thiol coated AuNPs (AuPEG).
      We show that both AuOEG and AuPEG particles carry a low net negative charge and
      are very stable (remaining so for more than one year), but long-term aging or
      dialysis can reduce the stability. If the decorated AuNPs are mixed with bovine
      serum albumin (BSA), both effective size and zeta-potential of the AuNPs remain
      unchanged, indicating no adsorption of BSA to the colloid surface. However, when
      mixed with lysozyme, zeta-potential values increase with protein concentrations
      and lead to a charge inversion, indicating adsorption of lysozyme to the colloid
      surface. The colloidal solutions of AuOEG become unstable near zero charge,
      indicated by a cluster peak in the DLS measurements. The AuPEG solutions show
      similar charge inversion upon addition of lysozyme, but the solutions are stable
      under all experimental conditions, presumably because of the strong steric effect
      of PEG. Washing the protein bound colloids by centrifugation can remove only part
      of the adsorbed lysozyme molecules indicating that a few proteins adsorb strongly
      to the colloids. The effective charge inversion and rather strongly bound
      lysozyme on the colloid surface may suggest that in addition to the charges
      formed at the SAM-water interface, there are defects on the surface of the
      colloid, which are accessible to the proteins. The results of this study of
      surface charge, and stability shed light on the interaction with proteins of SAM
      coated AuNPs and their applications. 

PMID- 24863764
TI  - Interactions of poly(dimethylsiloxane) with nanosilica and silica gel upon
      cooling-heating.
AB  - To control the properties of poly(dimethylsiloxane) (PDMS, Oxane 1000) as a bio
      inert material, the characteristics of Oxane 1000 were compared for PDMS alone
      and interacting with silica gel Si-100 and nanosilica PS400. Low-temperature (1)H
      NMR spectroscopy, applied to static samples at 200-300 K, and differential
      scanning calorimetry (DSC) at 153-393 K were used to analyze the properties of
      PDMS and composites. The NMR study shows that liquid and solid-like fractions of
      PDMS co-exist over a broad temperature range. The cooling-heating cycles give
      hysteresis loops of intensity of (1)H NMR signals of methyl groups of a liquid
      fraction of PDMS vs. temperature depending on the silica type. The loop width
      differs for PDMS alone and bound to silicas, and the samples preheated at 420 K
      are characterized by much narrower loops. DSC measurements of the samples show a
      significant difference in the thermograms on the first and second DSC scans that
      depend on the silica type. For PDMS confined in pores of silica gel, 3D spatial
      structure of the polymers can be more ordered than that of PDMS located in thin
      layers at a surface of nanosilica. Therefore, both melting endotherms and
      crystallization exotherms are observed for PDMS/silica gel. However, for
      PDMS/nanosilica, both thermal features are much weaker and observed during only
      the first DSC scan.

PMID- 24863765
TI  - Transparency microplates under impact.
AB  - Transparency microplates enable biochemical analysis in resource-limited
      laboratories. During the process of transfer, the analytes tittered into the
      wells may undergo spillage from one well to another due to lateral impact.
      Sidelong impact tests conducted found the absence of non-linear effects (e.g.,
      viscoelastic behavior) but high energy loss. Finite element simulations conducted
      showed that the rectangular plate holding the transparencies could undergo z-axis
      deflections when a normal component of the force was present despite constraints
      being used. High speed camera sequences confirmed this and also showed the
      asymmetrical z-axis deflection to cause the contact line closer to impact to
      displace first when the advancing condition was exceeded. Capillary waves were
      found to travel toward the contact line at the opposite end, where if the
      advancing contact angle condition was exceeded, also resulted in spreading. The
      presence of surface scribing was found to limit contact line movement better.
      With water drops dispensed on scribed transparencies, immunity from momentum
      change of up to 9.07 kgm/s on impact was possible for volumes of 40 MUL. In the
      case of glycerol drops immunity from momentum change of up to 9.07 kgm/s on
      impact extended to volumes of 90 MUL. The improved immunity of glycerol was
      attributed to its heightened dampening characteristics and its higher attenuation
      of capillary waves. Overall, scribed transparency microplates were able to better
      withstand spillage from accidental impact. Accidental impact was also found not
      to cause any detrimental effects on the fluorescence properties of enhanced green
      fluorescent protein samples tested.

PMID- 24863766
TI  - Covalently crosslinked fly ash/poly(acrylic acid-co-acrylamide) composite
      microgels as novel magnetic selective adsorbent for Pb2+ ion.
AB  - In order to improve the performance of treating waste-water with wastes, the
      magnetic fly ash (FA) particles were surface-modified with polymerizable groups
      as the crosslinker for the copolymerization with acrylic acid (AA) and acrylamide
      (AM) by a facile inverse suspension polymerization process, without any foreign
      organic crosslinker added. The optimized beadlike magnetic fly ash/poly(acrylic
      acid-co-acrylamide) composite microgels (FA/P(AA-AM)) with 3-dimensional
      crosslinking skeleton structure were selected as the magnetic selective microgel
      adsorbent for Pb(2+) ion, through a series of L(9)(3(4)) orthogonal experiments.
      It was found that the magnetic FA particles could improve the strength stability
      of the FA/P(AA-AM) composite microgels, also provide the ability of magnetic
      separation.

PMID- 24863767
TI  - Combining mercury thermoporometry with integrated gas sorption and mercury
      porosimetry to improve accuracy of pore-size distributions for disordered solids.
AB  - The typical approach to analysing raw data, from common pore characterization
      methods such as gas sorption and mercury porosimetry, to obtain pore size
      distributions for disordered porous solids generally makes several critical
      assumptions that impact the accuracy of the void space descriptors thereby
      obtained. These assumptions can lead to errors in pore size of as much as 500%.
      In this work, we eliminated these assumptions by employing novel experiments
      involving fully integrated gas sorption, mercury porosimetry and mercury
      thermoporometry techniques. The entrapment of mercury following porosimetry
      allowed the isolation (for study) of a particular subset of pores within a much
      larger interconnected network. Hence, a degree of specificity of findings to
      particular pores, more commonly associated with use of templated, model porous
      solids, can also be achieved for disordered materials. Gas sorption experiments
      were conducted in series, both before and after mercury porosimetry, on the same
      sample, and the mercury entrapped following porosimetry was used as the probe
      fluid for theromporometry. Hence, even if one technique, on its own, is indirect,
      requiring unsubstantiated assumptions, the fully integrated combination of
      techniques described here permits the validation of assumptions used in one
      technique by another. Using controlled-pore glasses as model materials, mercury
      porosimetry scanning curves were used to establish the correct correspondence
      between the appropriate Gibbs-Thomson parameter, and the nature of the meniscus
      geometry in melting, for thermoporometry measurements on entrapped mercury.
      Mercury thermoporometry has been used to validate the pore sizes, for a series of
      sol-gel silica materials, obtained from mercury porosimetry data using the
      independently-calibrated Kloubek correlations. The pore sizes obtained for sol
      gel silicas from porosimetry and thermoporometry have been shown to differ
      substantially from those obtained via gas sorption and NLDFT analysis. DRIFTS
      data for the samples studied has suggested that the cause of this discrepancy may
      arise from significant differences in the surface chemistries between the samples
      studied here and that used to calibrate the NLDFT potentials. 

PMID- 24863768
TI  - A simple and accurate method for calculation of the structure factor of
      interacting charged spheres.
AB  - Calculation of the structure factor of a system of interacting charged spheres
      based on the Ginoza solution of the Ornstein-Zernike equation has been developed
      and implemented on a stand-alone spreadsheet. This facilitates direct interactive
      numerical and graphical comparisons between experimental structure factors with
      the pioneering theoretical model of Hayter-Penfold that uses the Hansen-Hayter
      renormalisation correction. The method is used to fit example experimental
      structure factors obtained from the small-angle neutron scattering of a well
      characterised charged micelle system, demonstrating that this implementation,
      available in the supplementary information, gives identical results to the Hayter
      Penfold-Hansen approach for the structure factor, S(q) and provides direct access
      to the pair correlation function, g(r). Additionally, the intermediate
      calculations and outputs can be readily accessed and modified within the familiar
      spreadsheet environment, along with information on the normalisation procedure. 

PMID- 24863769
TI  - CdS urchin-like microspheres/alpha-Fe2O3 and CdS/Fe3O4 nanoparticles
      heterostructures with improved photocatalytic recycled activities.
AB  - The heterostructures of three-dimensional CdS urchin-like microspheres separately
      decorated with hematite alpha-Fe2O3 or magnetite Fe3O4 nanoparticles were
      successfully synthesized via a two-step solvothermal deposition. Each CdS urchin
      like microspheres had an average diameter of 2 MUm, which was composed of
      nanorods with average diameters of 10nm. alpha-Fe2O3 and Fe3O4 nanoparticles,
      with diameters of about 20 nm and 30 nm, respectively, anchored on the nanorods
      of CdS urchins. The photoluminescence behaviors of CdS urchins were conserved in
      both CdS/alpha-Fe2O3 and CdS/Fe3O4 heteronanostructures, and CdS/Fe3O4
      heteronanostructure displayed ferromagnetic properties of the Fe3O4
      nanoparticles, which makes it easily magnetically separated from the dispersion
      after photocatalysis and hence reused. Furthermore, the CdS/alpha-Fe2O3
      heteronanostructure exhibited superior photocatalytic performances under visible
      light irradiation over pure CdS urchins and both the heteronanostructures showed
      improved photocatalytic recycled activities.

PMID- 24863770
TI  - Spinous TiO2 and Au@TiO2 octahedral nanocages: amorphisity-to-crystallinity
      transition-driven surface structural construction and photocatalytic study.
AB  - Novel spinous TiO2 and Au@TiO2 octahedral nanocages have been prepared through a
      well-designed three-step strategy including templated TiO2 wet coating,
      subsequent structural ripening and final template removal or transformation. The
      strategy is built on an amorphisity-to-crystallinity transition-driven surface
      structural construction, which emphasizes the critical steps of crystallization
      controlled TiO2 coating and consequent structural ripening. The influence of some
      key parameters, such as coating temperature, ripening temperature and ripening
      time, on the structure and morphology of the spinous TiO2 and Au@TiO2 nanocages
      have been investigated. In addition, in photocatalytic measurements, the prepared
      spinous TiO2-based nanocages exhibit enhanced photocatalytic efficiency relative
      to spinousless TiO2-based nanocages as well as P-25, owing to their structure
      advantages resulting from spinous surfaces. The photocatalytic activity of these
      TiO2 based photocatalysts has been systematically studied through the
      corresponding .OH radical measurements. The synthetic strategy may work as a
      general method, through similarly designing, to realize surface structure
      engineering for various materials such as metals, hydroxide and other oxides
      besides TiO2.

PMID- 24863771
TI  - Insight into morphology and structure of different particle sized kaolinites with
      same origin.
AB  - The particle size, morphology, crystallinity order and structural defects of four
      kaolinite samples are characterized by the techniques including particle size
      analysis, scanning electron microscopy (SEM), X-ray diffraction (XRD), Raman
      spectroscopy, Fourier transform infrared spectroscopy (FTIR) and magic angle
      spinning nuclear magnetic resonance spectroscopy (MAS NMR). The particle size of
      four kaolinite samples gradually increases. Four samples all belong to the
      ordered kaolinite and show a decrease in structural order with the increase of
      kaolinite particle size. The changes of structural defect are proved by the
      increase of the band splitting in Raman spectroscopy, the decrease of the
      intensity of absorption bands in infrared spectroscopy, and the decrease of
      equivalent silicon atom and the increase of non-equivalent aluminum atom in MAS
      NMR spectroscopy. The differences in morphology and structural defect are
      attributed to the broken bonds of Al-O-Si, Al-O-Al and Si-O-Si and the Al
      substitution for Si in tetrahedral sheets. 

PMID- 24863772
TI  - Soft ligand stabilized gold nanoparticles: incorporation of bipyridyls and two
      dimensional assembly.
AB  - HYPOTHESIS: The synthesis of gold nanoparticles (AuNPs) in organic solvents
      without addition of surfactant may be achieved without the use of strong capping
      agents in the presence of soft ligands from the starting materials. Through post
      synthesis surface modification with ligands having moderate or strong affinity,
      the soft ligands should be displaced, allowing for manipulation of the AuNP size,
      size distribution, as well as the interparticle spacing. EXPERIMENTS: Synthesis
      of gold nanoparticles was undertaken using the reducing agent 9
      borabicyclo[3.3.1]nonane without addition of stabilizing ligands. Transmission
      Electron Microscopy (TEM) and X-ray Photoelectron Spectroscopy (XPS) were used to
      characterize the NPs. The interparticle spacing in 2D assemblies of the NPs was
      correlated with localized surface plasmon resonance (LSPR) shifts exhibited by
      the NPs in solution. FINDINGS: Soft-ligand-stabilized AuNPs in a size range of 3
      5 nm were generated at a slow rate. The soft ligands were found to be chloride
      (Cl(-)) ions and triethylphosphine (Et3P). Bipyridyl and thiol ligands displaced
      the weakly adsorbed soft ligands. Thiolate-stabilized AuNPs formed long range 2-D
      assemblies with regular interparticle spacing (edge-to-edge). UV-vis spectroscopy
      analysis shows the thiolated AuNPs exhibited an exponential localized wavelength
      (lambdamax) decay dependence on the alkylthiolate chain length, indicating an
      increase in the interparticle spacing.

PMID- 24863773
TI  - Facile routes of manufacturing silicon quantum dots on a silicon wafer and their
      surface activation by esters of N-hydroxysuccinimide.
AB  - Fluorescent silicon quantum dots (SiQDs) could be prepared by reduction of
      hydrogen silsesquioxane, etching of silicon powers with wetting chemistry
      techniques or electrolysis of a wafer catalyzed by polyoxometalates. Chemical
      modifications are indispensable for the stability of the SiQDs photoluminescence
      and wider applications of SiQDs. Facile routes of manufacturing SiQDs derived
      from a silicon wafer and its surface functionalization by N-hydroxysuccinimide
      (NHS) esters were described in this work in detail. Firstly, the porous silicon
      chip was prepared by nanosilver-assisted electroless chemical etching. Then the
      chip was etched successively with hydrofluoric acid/nitric acid solutions until
      it emitted dazzling red fluorescence which claimed the achieved SiQDs on silicon
      substrates (SiQDs/Si). Finally, surface NHS esters were fabricated on such an
      SiQDs/Si chipthrough stepwise modifications, which were tested by the amidation
      between the NHS esters and n-octylamine. The fluorescence emission of the
      SiQDs/Si chip almost remained unchanged during the successively chemical
      modifications, which indicated the SiQDs had capabilities of enduring the
      sustained high temperature and organic media. Meanwhile, the SiQDs did not leave
      from the silicon substrate during the surface tuning. The SiQDs obtained by
      ultrasonication of an SiQDs/Si chip in water were investigated by transmission
      electron and atomic force microscopies. 

PMID- 24863774
TI  - Fabrication of biconcave discoidal silica capsules and their uptake behavior by
      smooth muscle cells.
AB  - Biconcave discoidal silica microcapsules were fabricated by reaction of
      tetraethoxysilane (TEOS) on biconcave discoidal Ca(OH)2 templates, followed by
      core removal. The biconcave discoidal morphology of microcapsules was
      characterized by confocal laser scanning microscopy (CLSM) and transmission
      electron microscopy (TEM). The thickness of silica capsule shell can be tuned by
      two methods, "Gradient concentration" method and "Multi-step growth" method.
      Through the latter one, the shell thickness can be controlled more effectively.
      Compared with spherical microcapsules, the biconcave discoidal ones were
      internalized into smooth muscle cells (SMCs) with a slower rate. 

PMID- 24863776
TI  - Strings of polymer microspheres stabilized by oxidized carbon nanotubes.
AB  - Oxidized carbon nanotubes (CNTOs) with hydrophilic oxygen-containing functional
      groups and hydrophobic conjugated structure are prepared by the oxidation of
      carbon nanotubes (CNTs). After the polymerization of styrene with CNTOs dispersed
      in aqueous phase, polystyrene (PS) microspheres with string-like structure are
      obtained. Thermogravimetic analysis (TGA), differential scanning calorimeter
      (DSC) and Raman results indicate the strong interaction between the separated PS
      chains from the oil phase and CNTOs during the initial stage of the
      polymerization. These adsorbed PS chains on the surface of CNTOs are quickly
      swollen by the monomer and they grow in size during the further polymerization.
      The pH value and the ion strength of aqueous phase obviously affect the stability
      of PS microspheres. The particle size of microspheres is also determined by the
      pH. We demonstrate that the one-dimensional structure of CNTOs is responsible for
      the formation of polymer microspheres with special architecture. 

PMID- 24863775
TI  - Facile synthesis of three dimensional hierarchical Co-Al layered double
      hydroxides on graphene as high-performance materials for supercapacitor
      electrode.
AB  - A facile simple hydrothermal method combined with a post-solution reaction is
      developed to grow interconnected three dimensional (3D) hierarchical Co-Al
      layered double hydroxides (LDHs) on reduced graphene oxide (rGO). The obtained 3D
      hierarchical rGO-LDHs are characterized by field emission scanning electron
      microscopy, X-ray diffraction, and X-ray photo-electron spectroscopy. As LDHs
      nanosheets directly grow on the surface of rGO via chemical covalent bonding, the
      rGO could provide facile electron transport paths in the electrode for the fast
      Faradaic reaction. Moreover, benefiting from the rational 3D hierarchical
      structural, the rGO-LDHs demonstrate excellent electrochemical properties with a
      combination of high charge storage capacitance, fast rate capability and stable
      cycling performance. Remarkably, the 3D hierarchical rGO-LDHs exhibit specific
      capacitance values of 599 F g(-1) at a constant current density of 4 A g(-1). The
      rGO-LDHs also show high charge-discharge reversibility with an efficiency of
      92.4% after 5000 cycles.

PMID- 24863777
TI  - A molecular dynamics study of the force between planar substrates due to
      capillary bridges.
AB  - Molecular dynamics simulations are used to study capillary liquid bridges between
      two planar substrates and the origin, strength and range of the resulting force
      between them. Pairwise interactions are described by the Lennard-Jones potential.
      Surface wettability is tuned by varying the fluid-substrate well depth
      interaction parameter. The force between the substrates due to a bridge of liquid
      is estimated by different methods including non-equilibrium simulations of moving
      substrates connected by liquid bridges and macroscopic balance of forces. The
      latter involves knowledge of liquid-vapor interfacial free energy, curvature
      radii, radius of wetted area and contact angle at the triple-phase contact line.
      All these physical quantities are estimated from equilibrium simulations. The
      force is attractive when the substrates are solvophilic or moderately
      solvophobic; and thus for cavities surrounded by the same liquid the force is
      attractive even when the substrates are moderately solvophilic. Two threshold
      values for the fluid-substrate potential interaction parameter can be identified;
      one for which the effective interaction between substrates due to liquid bridges
      changes from repulsive to attractive and another for which the capillary bridge
      becomes mechanically unstable and breaks into droplets. 

PMID- 24863779
TI  - Microfluidic fabrication and permeation behaviors of uniform zwitterionic
      hydrogel microparticles and shells.
AB  - This study introduces a flexible and straightforward method for generating
      monodisperse complex hydrogel microparticles. For this, a water-in-oil emulsion
      was generated in a microcapillary device and then the emulsion drops were photo
      polymerized to transfer them to hydrogel particles. The hydrogel microparticles
      were made of poly (2-methacryloyloxyethyl phosphorylcholine) that has an enhanced
      biocompatibility due to the phosphatidyl choline moiety in the backbone. The
      average mesh size of the hydrogel network, which is 50A, was estimated on the
      basis of the Peppas-Merrill equation. This mesh size was experimentally confirmed
      again by NMR cryoporometry analysis and permeation test for dextran probes.
      Furthermore, to diversify the applicability of microfluidic technology, an oil-in
      water-in-oil double emulsion was also fabricated by using the co-axial jetting of
      three combined flows in the micro-channel. Then the aqueous shell was polymerized
      to give rise to hollow-structured hydrogel microparticles. Finally, we have shown
      that the microfluidic approach is useful for fabrication of complex hydrogel
      microparticles that have potential uses in drug immobilization and delivery. 

PMID- 24863778
TI  - Sorption of carbamazepine by commercial graphene oxides: a comparative study with
      granular activated carbon and multiwalled carbon nanotubes.
AB  - HYPOTHESIS: Graphene nanosheet materials represent a potentially new high surface
      area sorbent for the treatment of endocrine disrupting compounds (EDCs) in water.
      However, sorption behavior has been reported only for laboratory graphene
      prepared by a laborious and hazardous graphite exfoliation process. A careful
      examination of commercially available, clean, high-volume produced graphene
      materials should reveal whether they are appropriate for sorbent technologies and
      which physicochemical properties most influence sorption performance.
      EXPERIMENTS: In this study, three commercially available graphene oxide powders
      of various particle sizes, specific surface areas, and surface chemistries were
      evaluated for their sorption performance using carbamazepine and nine other EDCs
      and were compared to that of conventional granular activated carbon (GAC) and
      multi-walled carbon nanotubes (MWCNTs). FINDINGS: Sorption kinetics of
      carbamazepine on graphene oxide powders was rapid and reversible with alcohol
      washing, consistent with pi-pi interactions. The various sorption extents as
      described by Freundlich isotherms were best explained by available surface area,
      and only the highest surface area graphene oxide (771 m(2)/g) out-performed GAC
      and MWCNTs. Increasing pH caused more negative surface charge, a twofold decrease
      in sorption of anionic ibuprofen, a onefold increase in sorption of cationic
      atenolol, and no change for neutral carbamazepine, highlighting the role of
      electrostatic interactions.

PMID- 24863780
TI  - Physical adsorption of anisotropic titania nanoparticles onto poly(2
      vinylpyridine) latex and characterisation of the resulting nanocomposite
      particles.
AB  - Four poly(2-vinylpyridine) latexes with intensity-average mean diameters ranging
      between 246 and 955nm were prepared by aqueous emulsion polymerisation. These
      latexes were characterised by transmission electron microscopy, field emission
      scanning electron microscopy, dynamic light scattering, aqueous electrophoresis,
      disc centrifuge photosedimentometry and thermogravimetry. The adsorption of rice
      grain-shaped nano-sized titania particles onto the surface of these latex
      particles from aqueous solution was investigated. It was found that the titania
      particles adsorb strongly at pH 10 and the optimal loading and packing density of
      titania was investigated for each latex. The resulting core-shell P2VP-titania
      nanocomposite particles were characterised in terms of their titania contents,
      surface coverages and colloidal stabilities. UV-Vis spectra were recorded for the
      titania nanoparticles, the original P2VP latexes and the poly(2-vinylpyridine)
      titania nanocomposite particles. It was found that, for the larger nanocomposite
      particles, UV-Vis absorption was dominated by the latex core, whereas the smaller
      P2VP-titania nanocomposite particles exhibited UV attenuation to longer
      wavelengths compared to both the bare latex and the titania particles. The poly(2
      vinylpyridine) cores were selectively removed by calcination of the nanocomposite
      particles and the resulting hollow titania structures were investigated by
      transmission electron microscopy. 

PMID- 24863781
TI  - The distinct effects of Mn substitution on the reactivity of magnetite in
      heterogeneous Fenton reaction and Pb(II) adsorption.
AB  - In this study, a series of Mn substituted magnetites were synthesized and used in
      catalyzing the heterogeneous Fenton degradation of acid orange II and Pb(II)
      adsorption, in order to investigate the effect of Mn substitution on the
      reactivity of magnetite. The valence and local environment of both Fe and Mn in
      the spinel structure of magnetite were investigated by X-ray absorption fine
      structure (XAFS) spectroscopy. The incorporation of Mn did not change the valence
      and local structure of Fe in the synthetic magnetite, while Mn was in the
      valences of +2 and +3. The Mn distribution on the octahedral sites of magnetite
      surface increased with the increase in Mn content. The Mn introduction led to an
      improvement of catalytic activity of magnetite. The sample with the minimum Mn
      content displayed the best efficiency in OH production and the degradation of
      acid orange II, while the other substituted samples did not show obvious
      difference in their catalytic performance. The adsorption capacity of magnetite
      samples toward Pb(II) gradually increased with the increase in Mn content. The
      above influences of Mn substitution on the reactivity of magnetite were discussed
      in views of the variations in microstructural environment and physicochemical
      properties. 

PMID- 24863782
TI  - Attachment of micro- and nano-particles on tipless cantilevers for colloidal
      probe microscopy.
AB  - HYPOTHESIS: Current colloidal probe preparation techniques face several
      challenges in the production of functional probes using particles ?5 MUm.
      Challenges include: glue encapsulated particles, glue altered particle
      properties, improper particle or agglomerate attachment, and lengthy procedures.
      We present a method to rapidly and reproducibly produce functional micro and nano
      colloidal probes. EXPERIMENTAL: Using a six-step procedure, cantilevers mounted
      on a custom designed 45 degrees  holder were used to approach and obtain a
      minimal amount of epoxy resin (viscosity of ~14,000 cP) followed by a single
      micron/nano particle on the apex of a tipless cantilever. The epoxy and particles
      were prepared on individual glass slides and subsequently affixed to a 10* or 40*
      optical microscope lens using another custom designed holder. Scanning electron
      microscopy and comparative glue-colloidal probe measurements were used to confirm
      colloidal probe functionality. FINDINGS: The method presented allowed rapid and
      reproducible production of functional colloidal probes (80% success). Single nano
      particles were prominently affixed to the apex of the cantilever, unaffected by
      the epoxy. Nano-colloidal probes were used to conduct topographical,
      instantaneous force, and adhesive force mapping measurements in dry and liquid
      media conveying their versatility and functionality in studying nano-colloidal
      systems.

PMID- 24863784
TI  - A method to observe the structure of the interface between mesocarbon microbeads
      and pitch.
AB  - It is known that mesocarbon microbeads (MCMBs) have ordered structure and grow
      after absorbing molecules from pitch. However, the structure of pitch used for
      preparing MCMBs is disordered. Thus question of whether there is a region where
      the molecules absorbed from pitch change their orientations is a very interesting
      problem. In this paper, an interface between MCMBs and their pitch matrix has
      been found and the structure of the interface was observed by scanning electron
      microcopy. There are some ordered regions in the interface but the number of
      ordered regions in the interface is much fewer than the number inside the MCMBs.
      This indicates that the interface between the MCMBs and the pitch is the region
      where the orientations of the molecules absorbed from pitch change. 

PMID- 24863785
TI  - The pH dependent surface charging and points of zero charge. VI. Update.
AB  - The pristine points of zero charge (PZC) and isoelectric points (IEP) of metal
      oxides from the recent literature are summarized. This study is an update of the
      previous compilation (Kosmulski, 2009) and of its previous updates (Kosmulski,
      2009, 2011). Only the IEP of materials other than metal oxides are reported, and
      the PZC of such materials obtained by potentiometric titration and related
      methods are ignored. IEP of (nominally) CoO, Fe(OH)2, Gd2O3, Ni2O3, and Sb2O3
      have been reported in the recent literature. Those materials have not been
      studied before.

PMID- 24863783
TI  - Structural characterization of colloidal crystals and inverse opals using
      transmission X-ray microscopy.
AB  - A nondestructive tomographic technique was used to determine the crystallographic
      information of colloidal crystals comprising of polystyrene (PS) microspheres, as
      well as their silver inverse opals. The properties of the colloidal crystals,
      such as defects, grain size, grain boundaries, stacking sequence, and grain
      orientation, were determined using the full field transmission X-ray microscopy
      (TXM) with a spatial resolution of 50 nm. The PS microspheres (500-750 nm) which
      underwent a vertical electrophoresis process to form a face-centered cubic (fcc)
      close-packed structure with an ABCABC packing sequence. In addition, the
      colloidal crystal exhibited multiple grains, and an orientation variation of 6.1
      degrees  in the stacking direction between two neighboring grains.

PMID- 24863786
TI  - Effect of aniline on cadmium adsorption by sulfanilic acid-grafted magnetic
      graphene oxide sheets.
AB  - Cd(II) has posed severe health risks worldwide. To remove this contaminant from
      aqueous solution, the sulfanilic acid-grafted magnetic graphene oxide sheets
      (MGOs/SA) were prepared and characterized. The mutual effects of Cd(II) and
      aniline adsorption on MGOs/SA were studied. The effects of operating parameters
      such as pH, ionic strength, contact time and temperature on the Cd(II)
      enrichment, as well as the adsorption kinetics and isotherm were also
      investigated. The results demonstrated that MGOs/SA could effectively remove
      Cd(II) and aniline from the aqueous solution and the two adsorption processes
      were strongly dependent on solution pH. The Cd(II) adsorption was reduced by the
      presence of aniline at pH<5.4 but was improved at pH>5.4. The presence of Cd(II)
      diminished the adsorption capacity for aniline at pH<7.8 but enhanced the aniline
      adsorption at pH>7.8. The decontamination of Cd(II) by MGOs/SA was influenced by
      ionic strength. Besides, the adsorption process could be well described by pseudo
      second-order kinetic model. The intraparticle diffusion study revealed that the
      intraparticle diffusion was not the only rate-limiting step for the adsorption
      process. Moreover, the experimental data of isotherm followed the Freundlich
      isotherm model. 

PMID- 24863787
TI  - Mechanisms of mineral membrane fouling growth modulated by pulsed modes of
      current during electrodialysis: evidences of water splitting implications in the
      appearance of the amorphous phases of magnesium hydroxide and calcium carbonate.
AB  - Experiments revealed the fouling nature evolutions along different
      electrodialysis (ED) trials, and how it disappears when current pulsation acts
      repetitively on the interfaces of ion-exchange membranes (IEMs). Fouling was
      totally controlled on the diluate side of cation-exchange membrane (CEM) by the
      repetitive pulsation frequency of the higher on-duty ratios applied. They created
      steady water splitting proton-barriers that neutralized OH(-) leakage through the
      membrane, decreasing the interfacial pH, and fouling of the concentrate side. The
      anion-exchange membrane (AEM) on the diluate side was similarly protected, but it
      was fouled once water splitting OH(-) generation became either intense enough or
      excessively weak. Interestingly, amorphous magnesium hydroxide (AMH) stemmed on
      the CEM-diluate side from brucite under intense water splitting OH(-) generation,
      and/or strong OH(-) leakage electromigration through the membrane. Water
      dissociation and overlimiting current regimes triggered drastic water molecule
      removal from crystal lattices through an accelerated cascade water splitting
      reaction. Also, amorphous calcium carbonate (ACC) appeared on CEM under intense
      water splitting reaction, and disappeared once intense OH(-) leakage was allowed
      by the water splitting proton-barrier dissipation. Our findings have implications
      for membrane fouling control, as well as for the understanding of the growth
      behavior of CaCO3 and Mg(OH)2 species on electromembrane interfaces. 

PMID- 24863788
TI  - Modification of surface properties of cellulosic substrates by quaternized
      silicone emulsions.
AB  - The present work describes the effect of quaternization of silicones as well as
      the relevant treatment parameter pH on the frictional, morphological and
      relaxation properties of fabric substrates. Due to their unique surface
      properties, silicone polymers are extensively used to modify surface properties
      of various materials, although the effects of functionalization of silicones and
      relevant process conditions on modification of substrates are not well
      understood. Specifically we show a considerable reduction in fabric friction,
      roughness and waviness upon treatment with quaternized silicones. The treatment
      at acidic pH results in better deposition of silicone polymers onto the fabric as
      confirmed through streaming potential measurements which show charge reversal of
      the fabric. Interestingly, Raman spectroscopy studies show the band of C-O ring
      stretching mode at ~1095 cm(-1) shift towards higher wavenumber indicating
      lowering of stress in fibers upon appropriate silicone treatment. Thus along with
      the morphological and frictional properties being altered, silicone treatment can
      lead to a reduction in fabric strain. It is concluded that the electrostatic
      interactions play an initial role in modification of the fiber substrate followed
      by multilayer deposition of polymer. This multi-technique approach to study fiber
      properties upon treatment by combining macro to molecular level methods has
      helped in understanding of new functional coating materials.

PMID- 24863789
TI  - Nanoscale Zero-Valent Iron (NZVI) supported on sineguelas waste for Pb(II)
      removal from aqueous solution: kinetics, thermodynamic and mechanism.
AB  - In this study, the synthesis and characterization of a new adsorbent containing
      nanoscale zerovalent iron particles (NZVI) decorated sineguelas waste (S-NaOH
      NZVI) from agriculture biomass was investigated for the adsorption/reduction of
      inorganic pollution such as Pb(II) ions. The combination of ZVI particles on the
      surface of sineguelas waste can help to overcome the disadvantage of ultra-fine
      powders which may have strong tendency to agglomerate into larger particles,
      resulting in an adverse effect on both effective surface area and catalyst
      performance. The synthesized materials were characterized with different methods
      such as FT-IR, BET, XRD, TEM and pHPZC. Good dispersion of NZVI particles (ca. 10
      70nm) on the sineguelas waste was observed. The effects of various parameters,
      such as contact time, pH, concentration, adsorbent dosage and temperature were
      studied. The adsorption of Pb(II) ions has been studied in terms of pseudo-first-
      and second-order kinetics, and the Freundlich, Langmuir and Langmuir-Freundlich
      isotherms models have also been used to the equilibrium adsorption data. The
      adsorption kinetics followed the mechanism of the pseudo-second-order equation.
      The thermodynamic parameters (DeltaG, DeltaH and DeltaS) indicated that the
      adsorption of Pb(II) ions were feasible, spontaneous and endothermic at 25-80
      degrees C. XRD analysis indicated the presence of Pb(0) on the S-NaOH-NZVI
      surface. This study suggests that the modified sineguelas waste by NZVI particles
      can be prepared at low cost and the materials are environmentally benign for the
      removal of Pb(II) ions, and likely many other heavy metal ions, from water. 

PMID- 24863790
TI  - Magnetically-responsive electrophoretic silica organosols.
AB  - HYPOTHESIS: Silica nanoparticles can be dispersed in organic solvents
      (organosols) using surfactants, such as didodecyldimethylammonium bromide (DDAB).
      DDAB analogs prepared with lathanide tetrahalide counterions, either a high
      magnetic moment ion (HoCl3Br, DDAH) or low-magnetic moment one (NdCl3Br, DDAN),
      are expected to produce charged particles, but only DDAH-stabilized dispersions
      are expected to be magnetically responsive. EXPERIMENTS: Phase-analysis light
      scattering (PALS) measurements have been performed to determine the charge on
      DDAH- and DDAN-stabilized organosols. Magnetic sedimentation experiments have
      been performed to determine whether or not the silica dispersions are
      magnetically responsive. Sedimentation was monitored both by visual observations
      and UV-vis spectroscopy. FINDINGS: Both DDAH and DDAN organosols are negatively
      charged, the same as DDAB-stabilized nanoparticles. The DDAH-stabilized
      nanoparticles are found to respond to a magnetic field, whereas the DDAN
      stabilized nanoparticles do not. This opens up possibilities for creating
      nanoparticle dispersions in nonpolar solvents which can be tailored to respond to
      desired external stimuli.

PMID- 24863791
TI  - Influence of co-surfactants on crystallization and stability of solid lipid
      nanoparticles.
AB  - HYPOTHESIS: The purpose of this study was to find a suitable co-surfactant to
      replace non-food grade bile salts in solid lipid nanoparticle (SLN) formulations.
      The hypothesis was that the molecular structure and physical properties of co
      surfactant modulate the stabilization of SLNs upon polymorphic transition.
      EXPERIMENTS: Tristearin SLNs were prepared by using two main surfactants:
      saturated high-melting lecithin, and unsaturated low-melting lecithin. As co
      surfactants we used sodium taurodeoxycholate (i.e. bile salt), Pluronic F68,
      Tween 60 and 80, and amino acids tyrosine, tryptophan, and phenylalanine. The
      influence of co-surfactants on crystallization behavior and physical stability of
      SLNs was investigated by differential scanning calorimetry and static light
      scattering, respectively. FINDINGS: The results showed that the aromatic amino
      acids had optimal structures and properties to act as effective co-surfactants in
      SLNs. Our study suggests that ideal co-surfactants are amphiphilic with
      pronounced hydrophobic areas, but highly water soluble so that they can have a
      reservoir of molecules readily available for interfacial stabilization. They
      adsorb fast to the interfaces, but without inducing polymorphic transition. This
      work demonstrates how the right structure can facilitate the desired function.

PMID- 24863792
TI  - Same ligand--different binding: a way to control the binding of N-acetyl-cysteine
      (NAC) to Pt clusters.
AB  - The functionalization of "unprotected" Pt clusters with N-acetyl-cysteine (NAC)
      at different pH-values is presented that allows for binding NAC either via the
      thiol or the amide group to the particle. NMR-spectroscopy was used to study the
      chemical nature of NAC at weakly acidic and alkaline conditions. The formation of
      a cyclic isomer of NAC was found at high pH-values which occurs through an
      intramolecular reaction between the thiol and the amide group delivering a cyclic
      thioether. The absence of the bare thiol groups in aqueous alkaline solutions
      leads to binding of the cyclic isomer of NAC to the Pt clusters via its nitrogen
      atom. IR spectroscopy was applied, which confirmed that the cyclic isomer is,
      however, not stable upon drying, but undergoes ring-opening yielding the "normal"
      non-cyclic form. This distinctive property of NAC in combination with the use of
      "unprotected" clusters allows for binding the same ligand to clusters from the
      same batch, but with different binding modes, while the particle size is
      preserved. As a consequence, differences in the cluster properties can be related
      exclusively to the influence of the binding properties of the ligand. Finally,
      the catalytic hydrogenation of 2-butanone was used as a probe reaction and the
      resulting differences in the enantioselectivity can thus be related to this
      particular change in the binding mode. 

PMID- 24863793
TI  - In situ fabrication of electrochemically grown mesoporous metallic thin films by
      anodic dissolution in deep eutectic solvents.
AB  - We describe here a simple electrodeposition process of forming thin films of
      noble metallic nanoparticles such as Au, Ag and Pd in deep eutectic solvents
      (DES). The method consists of anodic dissolution of the corresponding metal in
      DES followed by the deposition on the cathodic surface. The anodic dissolution
      process in DES overcomes the problems associated with copious hydrogen and oxygen
      evolution on the electrode surface when carried out in aqueous medium. The
      proposed method utilizes the inherent abilities of DES to act as a reducing
      medium while simultaneously stabilizing the nanoparticles that are formed. The
      mesoporous metal films were characterized by SEM, XRD and electrochemical
      techniques. Potential applications of these substrates in surface enhanced Raman
      spectroscopy and electrocatalysis have been investigated. A large enhancement of
      Raman signal of analyte was achieved on the mesoporous silver substrate after
      removing all the stabilizer molecules from the surface by calcination. The highly
      porous texture of the electrodeposited film provides superior electro catalytic
      performance for hydrogen evolution reaction (HER). The mechanisms of HER on the
      fabricated substrates were studied by Tafel analysis and electrochemical
      impedance spectroscopy (EIS). 

PMID- 24863794
TI  - Hydrothermal synthesis and electrochemical performances of 1.7 V
      NiMoO4?xH2O||FeMoO4 aqueous hybrid supercapacitor.
AB  - One-dimensional (1D) NiMoO4?xH2O nanorods and beta-FeMoO4 microrods are
      successfully synthesized by simple hydrothermal method without using any organic
      solvents. X-ray diffraction (XRD) patterns reveal the single phase formation of
      nickel molybdate (NiMoO4?xH2O) and pure monoclinic phase of beta-FeMoO4. The
      growth of one dimensional morphology of both the molybdates are identified from
      scanning and transmission electron microscopes (SEM and TEM). The cyclic
      voltammogram envisage the pseudocapacitance behavior of NiMoO4?xH2O and beta
      FeMoO4 through the reversible redox reactions of Ni(3+)/Ni(2+) and Fe(3+)/Fe(2+)
      ions. An asymmetric supercapacitor is fabricated using NiMoO4?xH2O nanorods and
      beta-FeMoO4 as a positive and negative electrode, respectively. The beta
      FeMoO4||NiMoO4?xH2O asymmetric supercapacitor delivers a capacitance of 81 F g(
      1) at a current density of 1 mA cm(-2). The cell exhibits a high energy density
      of 29 W h kg(-1) and good cycling stability even after 1000 cycles.

PMID- 24863795
TI  - Effect of surfactant type on platinum nanoparticle size of composite Pt/alpha
      Al2O3 catalysts synthesized by a microemulsion method.
AB  - A facile method for the generation of platinum-on-alumina hybrid materials with
      high-surface area is presented, employing a microemulsion-based synthesis of
      metal nanoparticles. Pt nanoparticles (NPs) supported on alpha-Al2O3 were
      prepared by the reduction of metal ions in water-in-oil microemulsion systems
      stabilized by a range of different surfactants with cationic, anionic and
      nonionic headgroups, namely AOT, CTAB, Tween80 and TX-100. The synthesized
      materials were characterized using Fourier transform infrared spectroscopy (FT
      IR), X-ray diffraction (XRD) and scanning electron microscopy (SEM). It is
      demonstrated that choice of surfactant can be used to tailor the size of the
      generated Pt nanoparticles, and seen that surfactant charge has a determining
      role in this process. Pt NPs formed in microemulsion systems based on charged
      surfactants (AOT and CTAB) are smaller than those prepared in nonionic
      microemulsion systems (TX-100 and Tween80). A solvent-induced demixing process
      was used to cleanly obtain the hybrid materials from the reaction medium at low
      energy cost. 

PMID- 24863796
TI  - Facile one-pot synthesis of folic acid-modified graphene to improve the
      performance of graphene-based sensing strategy.
AB  - A convenient and environment-friendly method is reported to synthesize the
      reduced graphene oxide (rGO) sheets in aqueous solution using folic acid (FA) as
      both a reducing and stabilizing agent, to improve the performance of graphene
      based sensing strategy. The as-prepared FA-rGO sheets were characterized by
      transmission electron microscopy (TEM), UV-vis absorption spectroscopy, Fourier
      transform infrared (FT-IR) spectroscopy, Raman spectroscopy, X-ray diffraction
      (XRD) and thermogravimetric analysis (TGA), which provided the clear
      identification of the removal of oxygen-containing functional groups from the
      graphene oxide (GO) to form FA-rGO sheets. Further, it was found that the
      obtained FA-rGO sheets exhibited better biocompatibility and could act as the
      more efficient energy acceptor in long range resonance energy transfer (LrRET)
      process than that of graphene. Additionally, the FA-rGO can also catalyze the
      oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) by H2O2, and compared with GO
      sheets, they exhibited the more prominent intrinsic peroxidase-like activity,
      thus providing the more sensitive approach for colorimetric detection of H2O2. 

PMID- 24863797
TI  - Thermally sensitive reversible microgels formed by poly(N-Isopropylacrylamide)
      charged chains: a Hofmeister effect study.
AB  - In this study, we present a new method to obtain anionic and cationic stable
      colloidal nanogels from PNIPAM charged chains. The stability of the particles
      formed by inter-chain aggregation stems from the charged chemical groups attached
      at the sides of PNIPAM polymer chains. The particle formation is fully reversible
      that is, it is possible to change from stable polymer solutions to stable
      colloidal dispersions and vice versa simply by varying temperature. In addition,
      we also demonstrate that the polymer LCST (lower critical solution temperature),
      the final particle size and the electrokinetic behavior of the particles formed
      are highly dependent on the electrolyte nature and salt concentration. These
      latter results are related to Hofmeister effects. The analysis of these results
      provides more insights about the origin of this ionic specificity, confirming
      that the interaction of ions with interfaces is dominated by the
      chaotropic/kosmotropic character of the ions and the hydrophobic/hydrophilic
      character of the surface in solution. 

PMID- 24863798
TI  - Sol-gel hybrid films based on organosilane and montmorillonite for corrosion
      inhibition of AA2024.
AB  - The present work reports the production of films on AA2024-T3 composed of
      vinyltrimethoxysilane (VTMS)/tetraethylorthosilicate (TEOS) with incorporation of
      montmorillonite (sodium montmorillonite and montmorillonite modified with
      quaternary ammonium salt, abbreviated Na and 30B, respectively), generated by the
      sol-gel process. According to FT-IR analyses the incorporation of montmorillonite
      does not affect silica network. Electrochemical characterization was performed by
      electrochemical impedance spectroscopy measurement in 0.05 mol L(-1) NaCl
      solution. Results indicate that montmorillonite incorporation improves the
      corrosion protection compared to the non-modified system. Scanning electron
      microscopy micrographs reveal that high concentrations of montmorillonite provide
      agglomerations on the metallic surface, which is in detriment of the
      anticorrosive performance. The VTMS/TEOS/30B films with the lowest concentration
      (22 mg L(-1)) of embedded clay provide the highest corrosion protection.

PMID- 24863799
TI  - Butler-Sugimoto monomolecular bilayer interface model: the effect of oxygen on
      the surface tension of a liquid metal and its wetting of a ceramic.
AB  - The influence of oxygen on liquid-gas surface tension of molten metals has been
      well-investigated experimentally and modeled theoretically via the Szyszkowski
      equation, derivable from the Butler molecular monolayer interface model. However,
      there is no corresponding model describing the experimentally observed profound
      effect of oxygen partial pressure on solid-liquid surface tension as well as on
      contact angle of molten metals on ceramic substrates. Here, we utilize the Butler
      Sugimoto thermodynamic approach based on a monomolecular bilayer interface model
      to investigate the effect of oxygen partial pressure on liquid-gas as well as
      solid-liquid surface tension of molten Cu/Al2O3 and molten Ag/Al2O3 systems. It
      is shown that both liquid-gas and solid-liquid surface tension are a strong
      function of oxygen activity in the melt, which, in turn, depends on gas-phase
      oxygen partial pressure, in conformity with experiments. The change in solid
      liquid surface tension and wetting is also greatly affected by the change in
      liquid-gas surface tension. This improved understanding is of practical
      significance in many applications. 

PMID- 24863800
TI  - Removal of Cl adsorbed on Mn-Ce-La solid solution catalysts during CVOC
      combustion.
AB  - Mn-Ce-La oxide-mixed catalysts prepared by the method of complexation followed by
      calcination at 750 degrees C were tested in the catalytic combustion of
      chlorobenzene (CB) taken as a model of chlorinated aromatics. XRD analyses show
      that Mn and La enter CeO2 matrix with a fluorite-like structure to form solid
      solution. The catalysts with high ratio of Mn/Mn+Ce+La exhibit high activity for
      CB combustion, due to high oxygen mobility. For all Mn-Ce-La catalysts,
      deactivation due to Cl adsorption is observed at different temperatures,
      depending on composition. At 330 degrees C or higher temperature, the removal of
      Cl species from the surface in the forms of Cl2 (produced through Deacon
      reaction) and HCl (produced through hydrolysis of Cl) occurs and the activity of
      catalysts for CB combustion becomes thus stable. Either the addition of water or
      the increase in gaseous oxygen concentration can promote the removal of Cl
      species, and thus to increase the activity for CB combustion. High stable
      activity of Mn-Ce-La catalysts can be related to the combination of good
      oxidation and Deacon reaction performances. 

PMID- 24863801
TI  - Alterations in nanoparticle protein corona by biological surfactants: impact of
      bile salts on beta-lactoglobulin-coated gold nanoparticles.
AB  - The impact of biological surfactants (bile salts) on the protein (beta
      lactoglobulin) corona surrounding gold nanoparticles (200 nm) was studied using a
      variety of analytical techniques at pH 7: dynamic light scattering (DLS);
      particle electrophoresis (zeta-potential); UV-visible (UV) spectroscopy;
      transmission electron microscopy (TEM); and surface-enhanced Raman scattering
      (SERS). The bile salts adsorbed to the protein-coated nanoparticle surfaces and
      altered their interfacial composition, charge, and structure. SERS spectra of
      protein-coated nanoparticles after bile salt addition contained bands from both
      protein and bile salts, indicating that the protein was not fully displaced by
      the bile salts. UV, DLS and TEM techniques also indicated that the protein
      coating was not fully displaced from the nanoparticle surfaces. The impact of
      bile salts could be described by an orogenic mechanism: mixed interfaces were
      formed that consisted of islands of aggregated proteins surrounded by a sea of
      bile salts. This knowledge is useful for understanding the interactions of bile
      salts with protein-coated colloidal particles, which may be important for
      controlling the fate of colloidal delivery systems in the human gastrointestinal
      tract, or the gastrointestinal fate of ingested inorganic nanoparticles.

PMID- 24863802
TI  - Surface-modified bacterial nanofibrillar PHB scaffolds for bladder tissue repair.
AB  - The aim of the study is in vitro investigation of the feasibility of surface
      modified bacterial nanofibrous poly [(R)-3-hydroxybutyrate] (PHB) graft for
      bladder reconstruction. In this study, the surface of electrospun bacterial PHB
      was modified with PEG- or EDA via radio frequency glow discharge method. After
      plasma modification, contact angle of EDA-modified PHB scaffolds decreased from
      110 +/- 1.50 to 23 +/- 0.5 degree. Interestingly, less calcium oxalate stone
      deposition was observed on modified PHB scaffolds compared to that of non
      modified group. Results of this study show that surface-modified scaffolds not
      only inhibited calcium oxalate growth but also enhanced the uroepithelial cell
      viability and proliferation. 

PMID- 24863803
TI  - Prenatal diagnosis of maternally inherited X-linked Opitz G/BBB syndrome by
      chromosomal microarray in a fetus with complex congenital heart disease.
AB  - BACKGROUND: Prenatal sonographic diagnosis of Optiz G/BBB syndrome is difficult
      because the common clinical features, such as hypertelorism, hypospadias and
      abnormalities of midline structures, including laryngotracheoesophageal defects,
      are subtle. METHOD: Chromosomal microarray (CMA) analysis using a target enriched
      Fetal DNA Chip design was performed on the DNA of a fetus with congenital cardiac
      abnormalities. RESULTS: Fetal DNA chip revealed a 48Kb single copy number loss
      within chromosome region Xp22.2 (arr[hg18]Xp22.2(10,627,354-10,675,946)x0 mat).
      This deletion included the 3' UTR region of the MID1 gene predicted to cause the
      X-linked Opitz G/BBB syndrome. CONCLUSIONS: This case supports the use of CMA in
      prenatal diagnosis of fetuses with congenital heart disease. CMA allows prenatal
      diagnosis of genomic aberrations at a much higher resolution compared with
      conventional karyotyping, and such findings enable proper genetic counseling and
      decision making in the pregnancy.

PMID- 24863804
TI  - S100A8 as potential salivary biomarker of oral squamous cell carcinoma using
      nanoLC-MS/MS.
AB  - BACKGROUND: Oral squamous cell carcinoma (OSCC) shows low 5-year survival; early
      treatment greatly reduces mortality and morbidity. Saliva is a non-invasive
      sample, with good potential to discover biomarkers for early detection. METHODS:
      NanoLC-MS/MS served to analyze saliva proteome from control subjects (n=35) and
      OSCC patients T1 (n=29), T2 (n=36), T3 (n=14) and T4 (n=21) stages. Identified
      biomarkers were verified by Western blot and ELISA assays. RESULTS: NanoLC-MS/MS
      analysis of salivary proteins between 10 and 15kDa identified S100A8, hemoglobin
      delta and gamma-G globin in T3 and T4 stage OSCC as well as S100A7 in T1 and T2
      stage OSCC. Western blot and ELISA indicated positive correlation between
      salivary S100A8 increment and tumor size stage. High level of S100A8 appeared in
      3.4, 13.9, 92.9, and 100% of saliva OSCC patients with T1, T2, T3, and T4 stages,
      respectively. Significant increase of salivary S100A7 was observed in 20.7% and
      11.1% of those with T1 and T2, respectively. AUROC curve indicated high
      sensitivity, specificity and accuracy of S100A8-based ELISA as a detector.
      CONCLUSIONS: NanoLC-MS/MS, Western blot and ELISA manifested salivary S100A8 as a
      specific and sensitive marker for detection of OSCC patients. Salivary S100A8
      protein could be applicable in developing OSCC diagnostics.

PMID- 24863805
TI  - Detection of KRAS codon 12 and 13 mutations by mutant-enriched PCR assay.
AB  - BACKGROUND: The identification of KRAS mutations before the administration of
      anti-epidermal growth factor receptor (EGFR) therapy of metastatic colorectal
      cancer (mCRC) has become important. The aim of the present study was to develop a
      novel technology that can increase detection sensitivity for KRAS mutations.
      METHODS: DNAs were extracted from colorectal cancer tissues and formalin-fixed,
      paraffin-embedded (FFPE) colorectal cancer samples. Mutant-enriched PCR assay
      utilizes the exceptionally thermostable endonucleases, PspGI for codon 12 and
      PhoI for codon 13, for specific amplifying KRAS mutations from mixed samples. The
      amplified PCR products were subjected to single-base primer extension or
      sequencing. Digital PCR was used to evaluate some of the results. RESULTS: We
      compared the results with that from direct sequencing. In the FFPE samples,
      thirteen discordant samples were found. We showed that the mutant-enriched PCR
      assay can identify the codons 12 and 13 mutation in a mixed population of mutant
      and wild type DNA sequences at 1:1000 and 1:400, respectively. The sensitivity of
      this method is lower than the digital PCR. CONCLUSIONS: We developed a rapid and
      highly sensitive method to detect codons 12 and 13 mutations of the KRAS gene.
      This method is a powerful tool for finding low-abundance variations in genomic
      DNA.

PMID- 24863806
TI  - Prenatal exposure to the viral mimetic poly I:C alters fetal brain cytokine
      expression and postnatal behaviour.
AB  - An increased incidence of mental illness disorders is found in children and
      adolescents born to mothers who experienced an infection-based illness during
      pregnancy. Animal models to study the prenatal origin of such outcomes of
      pregnancy have largely used conventional rodents, which are immature (altricial)
      at birth compared with the human neonate. In this study, we used the precocial
      spiny mouse (Acomys cahirinus), whose offspring have completed organogenesis at
      birth, and administered a single subcutaneous injection of a 5 mg/kg dose of the
      viral mimetic poly I:C (polyriboinosinic-polyribocytidylic acid) at mid gestation
      (20 days; term is 39 days). Prenatal exposure to poly I:C caused a transient
      weight loss in the pregnant dam, produced a downregulation of the proinflammatory
      cytokine tumour necrosis factor-alpha in the fetal brain, and resulted in
      abnormalities in sensorimotor gating and reduced social interaction, memory and
      learning in juvenile offspring. No changes in exploratory activity or anxiety and
      fear behaviours were found between the treatment groups. This study provides
      evidence that, in a rodent model that more closely resembles human brain
      development, prenatal infection can lead to behavioural abnormalities in
      postnatal life.

PMID- 24863807
TI  - Practice plans of and factors influencing graduating dental students in China.
AB  - OBJECTIVES: The increasing number of dental schools and increasing annual dental
      undergraduate enrolment have resulted in stronger competition in job hunting
      among dental graduates. This study aimed to investigate the practice plans of
      graduating dental students and the factors influencing their practice choice.
      METHODS: Final-year dental students of Capital Medical University who graduated
      between 2009 and 2011 (n = 149) were invited to complete a self-administered
      questionnaire. The data were analysed using SPSS version 13.0. The Mann-Whitney
      test was used to analyse two independent samples, and the Kruskal-Wallis test was
      used for more than two samples. Fisher's exact test and the chi-squared test were
      also used to compare qualitative data. RESULTS: Among the respondents, 75.8% were
      female (n = 113) and 54.4% (n = 81) indicated that it was difficult to find an
      ideal practice position immediately following graduation. The three main
      contributing factors were the lack of employment opportunities (43%, n = 64),
      lack of work experience (40.9%, n = 61) and an inferior undergraduate degree
      (26.8%, n = 40). Among the respondents, 55.7% (n = 83) planned to pursue further
      study at university, whereas 44.3% (n = 66) planned to enter clinical practice.
      We also investigated the level and type of sectors in which respondents
      anticipated practicing, as well as the conditions that attracted respondents to
      practice in community health service centres. CONCLUSIONS: Our findings have
      implications for dental educators, administrators and policy makers as they
      attempt to recruit qualified dental graduates to meet the nation's future dental
      health-care needs and advance the profession of dentistry.

PMID- 24863809
TI  - Transcriptional and epigenetic control of IGF1R gene expression: implications in
      metabolism and cancer.
AB  - IGF1R plays an important role in protection from apoptosis, regulation of cell
      growth, differentiation and oncogenic transformation. IGF1R aberrations lead to
      intrauterine and postnatal growth failure, microcephaly, mental retardation and
      deafness. High levels of IGF1R are detected in a diversity of human tumors. IGF1R
      gene transcription is controlled by complex interactions involving DNA-binding
      and non DNA-binding transcription factors. This review highlights selected
      examples of a series of tumor suppressors, including the breast cancer gene-1
      (BRCA1), p53, the Wilm's tumor protein-1 (WT1) and the von Hippel-Lindau gene
      (VHL), whose mechanisms of action involve regulation of IGF1R gene expression.
      IGF1R gene transcription is also dependent on the presence of stimulatory nuclear
      proteins, including zinc-finger protein Sp1, EWS-WT1, E2F1, Kruppel-like factor-6
      (KLF6), high-mobility group A1 (HMGA1), and others. Loss-of-function of tumor
      suppressor genes, usually caused by mutations, may result in non-functional
      proteins unable to control IGF1R promoter activity. Impaired regulation of the
      IGF1R gene is linked to defective cell division, chromosomal instability and
      increased incidence of cancer. 

PMID- 24863810
TI  - [National Health Survey in Brazil: design and methodology of application].
AB  - The National Health Survey is a household-based nationwide survey carried out by
      the Ministry of Health in partnership with the Brazilian Institute of Geography
      and Statistics. The scope of the survey is to establish the health status and
      lifestyles of the population - as well as how they look after their health - with
      regard to access and use of services, preventive actions, continuity of care, and
      health care financing. The sample size is 80,000 households and enables the
      calculation of some indicators at different geographic levels, namely states,
      capitals, metropolitan and rural areas. The questionnaire is divided into three
      parts. The first two are answered by one resident and include questions on the
      household characteristics and on the social and economic level and health status
      of all inhabitants. The individual questionnaire is answered by an adult (aged 18
      years or more), selected with equal probability among the adult residents, and
      focuses on morbidity and lifestyle. For this individual, measurements of weight,
      height, waist circumference and blood pressure are taken, as well as laboratory
      exams to characterize the lipid profile and blood glucose level, as well as
      determine the urine sodium content. The laboratory exams are taken in a subsample
      of 25% of the census sectors selected. 

PMID- 24863808
TI  - Investigation of galectin-3 function in the reproductive tract by identification
      of binding ligands in human seminal plasma.
AB  - PROBLEM: Galectin-3 is a beta-galactoside binding protein with immunomodulatory
      properties and exerts its extracellular functions via interactions with
      glycoconjugate ligands. Therefore, to elucidate the function of galectin-3,
      binding ligands in human seminal plasma were investigated. METHOD OF STUDY:
      Galectin-3 binding proteins were isolated from seminal plasma by affinity
      chromatography, and candidate ligands were identified by MS/MS. Biochemical
      methods were used to characterize the ability of galectin-3 to bind its ligands.
      RESULTS: Identified galectin-3 ligands included CD13, MUC6, PAP, PSA, and ZAG. 1D
      and 2D electrophoretic analysis of seminal plasma demonstrated that CD13, PAP,
      PSA, and ZAG immunoreactivity co-migrated with galectin-3-reactive protein bands
      and spots at expected molecular weights and pIs. Inhibition assays indicated that
      CD13, PSA, PAP, and ZAG interact with galectin-3 in a protein-carbohydrate
      manner. CONCLUSION: The galectin-3 binding ligands identified in this study
      indicate multiple roles for galectin-3 in the reproductive and immunological
      functions of seminal plasma.

PMID- 24863811
TI  - [Primary Health Care in the coordination of health care networks: an integrative
      review].
AB  - Health systems organized in health care networks and coordinated by Primary
      Health Care can contribute to an improvement in clinical quality with a positive
      impact on health outcomes and user satisfaction (by improving access and
      resolubility) and a reduction in the costs of local health systems. Thus, the
      scope of this paper is to analyze the scientific output about the evidence,
      potential, challenges and prospects of Primary Health Care in the coordination of
      Health Care Networks. To achieve this, the integrative review method was selected
      covering the period between 2000 and 2011. The databases selected were Medline
      (Medical Literature Analysis and Retrieval System online), Lilacs (Latin American
      Literature in Health Sciences) and SciELO (Scientific Electronic Library Online).
      Eighteen articles fulfilled the selection criteria. It was seen that the
      potential impacts of primary care services supersede the inherent weaknesses.
      However, the results revealed the need for research with a higher level of
      classification of the scientific evidence about the role of Primary Healh Care in
      the coordination of Health Care Networks. 

PMID- 24863812
TI  - [Evaluation of the family focus and community orientation in the Family Health
      Strategy].
AB  - The Family Health Strategy should be focused on the family unit and constructed
      operationally within the community sphere. The research assessed the family focus
      and community orientation as attributes of Primary Health Care, comparing if the
      responses differed among users, professionals and managers. It is an evaluative
      study of a population-based quantitative approach conducted between January 2010
      and March 2011 in Sao Luis in the state of Maranhao. The study involved a
      population of 32 managers and 80 professionals with more than six months
      experience in the Family Health Strategy, and 883 users were selected by means of
      cluster sampling. Questionnaires validated in Brazil were used based on the
      components of the Primary Care Assessment Tool (PCATool). The composite index of
      the family focus was 2.7 for users, 4.9 for professionals and 5.3 for managers.
      In the posttest phase, differences were detected between users and professionals,
      and users and managers. The composite index of community orientation was 2.9 for
      users, 3.9 for professionals and 4.8 for managers (p < 0.001). Managers
      attributed higher percentages in all indicators, followed by professionals and
      lastly users. Both attributes were rated as being unsatisfactory in the
      perception of the users. 

PMID- 24863813
TI  - [Primary Care and maternal and child health: perceptions of caregivers in a rural
      'quilombola' community].
AB  - This study sought to evaluate the attributes of primary care, with a focus on
      child health, from the viewpoint of a 'quilombola' community in the north of the
      state of Minas Gerais, Brazil (A quilombola is a resident of a quilombo in
      Brazil. They are the descendents of Afro-Brazilian slaves who escaped from slave
      plantations that existed in Brazil until abolition in 1888). It is a cross
      sectional, descriptive study with a quantitative approach. The Primary Care
      Assessment Tool (PCA-Tool, child version) was used and applied to the main
      caregivers of child residents duly registered in the quilombola community. The
      attributes of primary care were assessed using scores awarded by caregivers,
      according to the criteria of the instrument. Only two attributes of primary care
      revealed satisfactory values: Access-Use and Information Coordination-System. The
      lowest scores were for the attributes of Family Guidance and Access
      accessibility. The overall score was also below the satisfactory assessment. The
      results register low fidelity to attributes of primary care, as perceived by
      caregivers, and highlight the need for greater efforts to adapt the new model of
      care for the population under scrutiny. 

PMID- 24863814
TI  - [The inclusion of the oral health team in the Brazilian Family Health Strategy:
      barriers, advances and challenges].
AB  - This scope of this article is to discuss the inclusion of oral health in the
      Brazilian Family Health Strategy in municipalities of a micro-region of
      southeastern Brazil, from the standpoint of human resources. Questionnaires were
      distributed to members of the oral health service: dentists, assistants and
      managers. The instrument included three dimensions: how and why they adopted the
      new model; how the service is being reorganized; and what advances were perceived
      by professionals. The most common reason mentioned by managers for the inclusion
      of Oral Health was the possibility of changing the technical care model. When
      asked about their motivation, dentists and assistants also considered the
      possibility of change in practices to be a priority. It was also seen that there
      are critical bottlenecks in the hiring and training of human resources to work in
      the oral health team and in integration among health professionals. Indeed,
      access is enhanced either by the organization or by the expansion of the teams.
      The municipalities of the micro-region still encounter difficulties for the
      functioning of the oral health service, after Family Health, to show actual
      progress in care practices. However, advances exist and these need to be
      bolstered to consolidate the health system and improve the quality of life of the
      population. 

PMID- 24863815
TI  - [Resolubility in oral health for primary care as an instrument for the evaluation
      of health systems].
AB  - This study sought to evaluate which health system - either the Family Health
      Strategy (FHS) or the traditional model established in the Basic Health Units
      (BHU) - was more effective during the period between 2007 and 2009 in relation to
      the oral health needs of the population of the city of Marilia in the state of
      Sao Paulo. It involved a retrospective ecological study with a stratified random
      sample of 50% of the universe of the study area for the 12 BHU and 37% of the 29
      Family Health Units (FHU) in the municipality, whereby 6 BHU and 11 FHS were
      randomly selected. The data collected for observation were gathered through the
      management reports of the SIAB and Oral Health Assessment Report information
      systems. Exploratory data analysis and the Student t test were performed in order
      to analyze the resolubility of different systems of health care. It was observed
      that the coefficients relating to Initial Dental Treatment were not statistically
      different, though with respect to the Completed Initial Treatment coefficient for
      the population greater than two years the values were 16.74 for the FHS model and
      6.93 for the BHU model, with a statistically significant difference of 40.97%
      resolubility for the BHU in relation to 83.56% for the FHS (p < 0.05). 

PMID- 24863816
TI  - [Profile of Primary Health Care managers in small municipalities in the north of
      the state of Parana, Brazil].
AB  - The scope of this article was to establish the profile of Primary Health Care
      (PHC) managers in 49 small municipalities (up to 20,000 inhabitants) in the north
      of the state of Parana. A semi-structured questionnaire was applied to 90
      managers in a quantitative-based study. For statistical analysis the EpiInfo
      3.5.1. program was used. The results of the manager profile showed that 91.1%
      were women, 83.3% nurses, 50% aged 21 to 30 years and 75.6% with specialization.
      Concerning the entry into employment, 70% were through public exam/selective
      test. Regarding professional experience, 40% had worked professionally for more
      than 5 years, 43.4% had been involved in PHC up to 5 years and 32.2% had been in
      the current primary health care unit for less than 1 year. Regarding specific
      training for performing a managerial role, 71.1% had not taken any courses; only
      23.3% reported having taken a management course, though 37.7% had already acted
      as managers. The conclusion reached is that there is a lack of professionalism,
      training and institutionalization of the position for the performance of this
      function. 

PMID- 24863817
TI  - [Adherence to the Ongoing Education Program for family doctors in a southeastern
      Brazilian state].
AB  - Ongoing Health Education is a strategy for transformation of health practices,
      though the adherence of professionals is one of the challenges facing its
      implementation. Thus, the objective of this study was to investigate the factors
      associated with adherence of family doctors to the Ongoing Education Program in a
      southeastern Brazilian state from the perception of supervisors. It is a cross
      sectional and quantitative study with the use of online questionnaires. Data were
      analyzed using the chi-square test with ongoing correction to determine the
      association between structure, topics, activities and difficulties of the
      supervisors working in Ongoing Health Education, difficulties of the physicians
      in Primary Health Care (PHC) and poor and good adherence to the program.
      Excellent medical participation was statistically related to the adequacy of
      physical space (p = 0.001), a multidisciplinary approach (p = 0.035) and
      epidemiological aspects (p = 0.043). Low adherence was associated with the
      inadequacy of the physical structure, difficulty understanding the methodology,
      less time in a supervisory position, multiple workdays, among others. A good
      adherence to Ongoing Health Education is a possibility for collective
      reconstruction of the everyday work of physicians in Primary Health Care. 

PMID- 24863818
TI  - [Significances of health and ways of taking care of oneself prepared by male
      frequenters of Basic Health Units - UBS].
AB  - The research sought to understand the significances of health and ways of taking
      care of oneself prepared by male frequenters of a Basic Health Unit - UBS in
      Manaus. The method used was qualitative research through semi-structured
      interviews with male frequenters and healthcare professionals of a UBS located in
      the outskirts of Manaus in the state of Amazonas. Data were analyzed using
      techniques of Thematization, Content Analysis and Significance Processing based
      on the Social Constructivist approach proposed by Spink. The research revealed
      the multifaceted issues of gender, which show that men "are not all equal," as
      there are various types of masculinities. The men interviewed in the health
      service showed that there are significances of health that they share with each
      other, but they also differ in many dimensions. The survey reflected that the
      plurality of significances of health and the ways of taking care of oneself
      confer a human character upon health and claim the proactive role of frequenters
      in the construction of a system of comprehensive health care. They point to
      indicators that can contribute to interventions in health for increasing the
      visibility of men in the health services and consequently the ability of the
      services to deal with them. 

PMID- 24863819
TI  - [Men's health care in the scope of the Family Health Strategy].
AB  - The National Policy of Comprehensive Care for Men's Health created the guidelines
      for the strategies and actions based on comprehensive care, seeking the promotion
      of health and the prevention of disease duly focused as core issues of the Family
      Health Strategy (FHS). This article describes the specificities of men's health
      care in the context of the FHS from the standpoint of the manager, the demands of
      the men linked to the health units assessed and the practices adopted by the
      teams. Men's health care was evaluated by interviews with 43 FHS team managers
      (FHST), systematically selected considering the geographical region, city size
      and FHS coverage; and by interviewing 86 adult men of the respective FHS coverage
      area. It was seen that the strategy of the FHST is to address the health-disease
      process in the family and environmental context. However, in men's health there
      are still several gaps, from the adaptation of the structure of primary health
      care through to the motivation and development of actions against the most common
      health problems of this population group. This situation sometimes limits men's
      access to health services thereby negating the goal of the Policy. 

PMID- 24863820
TI  - [Actions geared to tobacco control: a review of their implementation in Primary
      Health Care].
AB  - This survey examined the status of the implementation of policies for tobacco
      control in a medium-sized municipality through an assessment of actions
      recommended by the National Tobacco Control Program (NTCP) promoted by Primary
      Health Care (PHC) units. The coordinator of the local NTCP and professionals from
      44 PHC units of Juiz de Fora in the state of Minas Gerais were interviewed,
      between May and July 2011. It was observed that the actions of treatment and
      health promotion were being duly executed, the highlight being the training of
      professionals to implement treatment in PHC. In 40.9%, there is the provision of
      treatment for smokers, and in 88.6% the actions are concentrated in activities in
      waiting rooms, groups and individual consultations. Limitations identified are
      probably not restricted to the municipality, such as inadequate structuring of
      units, high turnover, the varying degree of involvement of professionals in
      implementing the service and also the lack of mechanisms to enable them to
      implement and give continuity to care among their other responsibilities. The
      major challenge for tobacco control is to conduct intersectoral actions and in
      primary health care. The results can serve for the formulation of strategic
      health actions in other parts of the country. 

PMID- 24863821
TI  - [Preventive and interceptive orthodontics in the primary health care network of
      the Brazilian Unified Health System: the viewpoint of the dental surgeons of
      Florianopolis City Hall].
AB  - The scope of this exploratory study was to understand the viewpoint of the dental
      surgeons of the Primary Health Care (PHC) network in Florianopolis regarding the
      need, feasibility and interest in broadening preventive orthodontic services and
      in the implementation of interceptive orthodontics. A structured questionnaire
      was used to establish the viewpoint of all the primary care dental surgeons who
      perform clinical care in the network. The results indicate that: the majority are
      in favor provided that there is an appropriate structure to attend the needs of
      the population; the professionals consider themselves unqualified to perform the
      requisite procedures, so training would be necessary; there would be no need to
      deploy other orthodontic procedures in primary care than those analyzed; and the
      main difficulties that might be encountered were related to excess demand and the
      lack of human resources. Despite these obstacles, the majority of the
      professionals consider it positive and feasible to introduce this service, which
      could increase the comprehensiveness of health care and bolster primary care,
      thereby improving the health of the population. 

PMID- 24863822
TI  - [Self-reported morbidity by workers in the Family Health Teams].
AB  - The health of primary care workers is still a poorly addressed area of study in
      Brazil. The scope of this study was to describe the standard of self-reported
      morbidity by workers in Family Health Teams (FHT) in the northeastern macro
      region of the state of Minas Gerais. A cross-sectional study was conducted with
      self-applied questionnaires, including socio-demographical data, labor and health
      conditions, among all workers in FHT. Self-reported morbidity was categorized
      based on the International Classification of Primary Care, version 2. Information
      was collected from 1,731 workers in 204 primary health care units. The group was
      predominantly comprised of female community health workers. The prevalence of at
      least one health problem was 26.1% for women and 18.3% for men. The main health
      problems were related to circulatory, musculoskeletal, respiratory, endocrine
      metabolic and nervous systems. After multiple analysis, the variables associated
      with health problems were related to being female, aged 30 years or more and
      being on the team for 5 years or longer. The morbidity reported by the FHT
      workers is similar to that observed for the population in general, highlighting
      the need for strategies to promote the health of these workers as well. 

PMID- 24863823
TI  - The International Classification of Functioning, Disability and Health: progress
      and opportunities.
AB  - The International Classification of Functioning, Disability and Health is a tool
      used to monitor individuals from a broad perspective, which considers not only
      their health but also the biopsychosocial aspects involved in the health-disease
      process. It offers a range of categories to describe the aspects of human
      functioning that interfere with the performance of activities, as well as the
      environmental aspects that facilitate or hamper participation, integration and
      consequently quality of life. This paper reports some of the experiments in the
      use of this classification as a way to foster its use and show the broad range of
      possibilities offered by this tool. The disclosure of usage strategies will make
      it more well-known and adopted, opening up new perspectives for the health care
      segment. 

PMID- 24863824
TI  - [Contradictions of public health policies geared to rare disorders: the example
      of the Osteogenesis Imperfecta Treatment Program in the Brazilian Unified Health
      System (SUS)].
AB  - The scope of this paper is to examine the process of consolidation of a public
      health policy in Brazil geared to a rare disorder, namely osteogenesis
      imperfecta, the treatment for which has fallen under the responsibility of the
      Brazilian Unified Health System (SUS) after the publication of Ministerial Ruling
      GM/MS2305/2001. The implementation of this law has been accompanied by many
      contradictions, especially with respect to therapeutic decisions and the
      strengthening of the specialized network for addressing this condition. These
      attitudes are clearly shown both by the drafting process and the final text of
      the new law (Ministerial Ruling 714/2010). 

PMID- 24863825
TI  - [The interface between public health and cyberculture].
AB  - This is an opinion piece that proposes a reflection on the current status of the
      interface between cyberculture and public health and its use as a means for
      research, not as a mere tool. Cyberculture thus represents a new form of
      interface between people. And it is precisely "through" and "by means of" social
      relations that individuals acquire skills and communication techniques. The forms
      and the means of the relationship alters, but the ends remain unchanged, namely
      to be in contact with other humans. In recent decades, with the advent of
      computers, the Internet and all the technological apparatus, human relationships
      are dependent on them, which is the modern so-called cyberculture. This now
      affects all areas of activity, and public health cannot be left behind, taking
      advantage of it and its benefits for its development. It is necessary to keep
      abreast of these changes and raise them from the theoretical to the practical
      plane, not only implementing public health policies but also taking the socio
      virtual aspects into consideration. It is also necessary for the professionals
      involved to be updated on new forms of communication, interaction, research
      methodology, preparation of instruments, sampling approaches and all other
      phenomena arising from cyberculture that will work in partnership with public
      health. 

PMID- 24863826
TI  - [Social participation and health in Brazil: a systematic review on the topic].
AB  - The process of democratization of Brazil contributed to the emergence of
      management councils and thematic conferences in the context of public health
      policies. The scope of this article was to conduct a systematic review of the
      literature in order to establish the factors associated with the process of
      institutionalization of these democratic areas. The following databases were
      researched: LILACS, IBECS, MEDLINE, SciELO, PAHO, PsycINFO, Web of Science,
      Social Science and EBSCO. For the composition of the sample of 25 articles, the
      following key words were used: Social Control, Social Participation, Consumer
      Participation, Community Participation, Public Participation, Citizen
      Participation, Political Participation, Participative Management, Participative
      Democracy, Deliberative Democracy with Health Councils and Health Conferences.
      The results found synthesize a set of categories that has impacted the
      participatory public spaces: political representation and qualification,
      relationships among the social actors, institutional design, political culture,
      discourses about health/disease and the debate about democracy. The findings help
      to move forward in the understanding of such institutions, fostering the
      construction of alternatives committed to the strengthening of democracy in
      Brazil. 

PMID- 24863827
TI  - [Health policies for tobacco control in Latin America and the Caribbean: an
      integrative review].
AB  - The habit of smoking is an increasing concern for governments, health authorities
      and society as a whole, as it is a legal drug, which is addictive and leads to
      serious damage to health. Cigarette smoking causes about 5.4 million deaths/year
      worldwide and is the second major risk factor for deaths. An attempt is made to
      identify how policies can contribute to the eradication of smoking in Latin
      America and the Caribbean. An integrative review was conducted at BIREME using
      LILACS, and 16 articles were selected using inclusion and exclusion criteria. The
      articles were compared and grouped according to similarity of content and divided
      into 4 groups: smoke-free spaces, Framework-Convention, local Brazilian policies
      and others. Little data about smoking in Latin America and the Caribbean is
      available, mainly with respect to the evaluation of policies deployed. Policies
      for smoke-free spaces were emphasized (5 articles), as well as the Framework
      Convention on tobacco control (4 articles) and articles that portray Brazilian
      policies for tackling smoking (3 articles). 

PMID- 24863828
TI  - [Infectious diseases among Brazilian preschool children attending daycare
      centers].
AB  - The scope of this article is to analyze the prevalence and factors associated
      with the development of infectious diseases that affect children in daycare
      centers, namely respiratory infections, diarrheal disease and parasitic
      infections. Bibliographic research was conducted in the MEDLINE, LILACS and
      SciELO databases, and observational studies were included. 129 studies were
      identified, of which 21 were considered relevant to this study, namely two
      longitudinal and 19 cross-sectional studies. The systematization of the reviewed
      studies highlighted: i) the presence of intestinal parasites was the main outcome
      analyzed, followed by respiratory infections; ii) only one study investigated the
      occurrence of diarrheal disease; iii) the Giardia lamblia was the most prevalent
      parasitosis; iv) the variables that were most often associated with the
      development of intestinal parasitosis were child age, family income and maternal
      education; v) the attendance at daycare centers was a risk factor for intestinal
      parasites and respiratory infections. Respiratory and parasitic infections are
      major problems in institutionalized children in daycare centers. The reduction of
      such diseases involves a complex web of socio-economic, sanitation and daycare
      center infrastructure aspects. 

PMID- 24863829
TI  - [Nutritional counseling for children under two years of age: opportunities and
      obstacles as strategic challenges].
AB  - This article sought to conduct a critical analysis of the state of the art of the
      scientific production in counseling practices in nutrition for infants under two
      years of age, discussing the opportunities and obstacles in terms of strategic
      challenges for implementing healthy nutrition practices. It is a bibliographic
      study, with the core interest being counseling on infant nutrition. The majority
      (58.1 %) of the articles analyzed was published between 2008 and 2011. The
      educative actions of counseling on infant feeding were directed at health
      professionals and caregivers to children under two years of age. As opportunities
      in the practice of nutritional counseling the following stand out: an improvement
      in the performance of health professionals, the adoption of healthy eating
      practices by caregivers, and an improvement in the nutritional status of the
      children. As obstacles, the following stand out: a lack of training of caregivers
      and professionals regarding complementary healthy feeding and difficulties
      regarding the practice of counseling by a health care professional. This evidence
      reaffirms the importance of incorporating counseling guidance on infant feeding,
      as permanent practices in policies for child health care. 

PMID- 24863830
TI  - [Combating smoking in Brazil: the strategic importance of government actions].
AB  - Brazil is a world benchmark in combating smoking and promoting actions through
      the National Program for Tobacco Control and other Risk Factors for Cancer
      (PNCTOFR). This literature review was conducted in order to outline the actions
      of PNCTOFR and identify evidence of their effectiveness in reducing the
      prevalence of smoking in Brazil. The documents available in the electronic
      portals of INCA, the National Policy on Health Promotion, the National Tobacco
      Control Observatory, the World Health Organization and the Pan American Health
      Organization were used, in addition to the Lilacs, PubMed Central, SciELO and
      ScienceDirect databases. The reference bases for analysis of the actions were the
      areas/dimensions proposed by the International Union for Health Promotion and
      Education. The restriction of the availability, control of marketing and
      commercialization, educational activities in schools, assistance in primary care
      for health professionals and the general population, control of consumption in
      public places and work are some of the actions that contributed to reduction in
      the prevalence of smoking in Brazil from 32.7% in 1997 to 14.8% in 2011. The
      results indicate the effectiveness of the actions of PNCTOFR, albeit smoking is
      still a public health problem and needs to be curbed. 

PMID- 24863831
TI  - [Prevalence of non-nutritive sucking habits in preschoolers and parents'
      perception of its relationship with malocclusions].
AB  - This cross-sectional and descriptive study sought to verify the prevalence of
      sucking habits in preschoolers and their parents' perception of its relationship
      with the occurrence of malocclusion. The population consisted of a representative
      sample of parents of preschoolers aged between 4 months and 6 years old. A semi
      structured, self-administered questionnaire was used, consisting of open and
      closed questions relating to frequency of use and knowledge of parents regarding
      non-nutritive sucking habits. Of the 356 respondents, 70.8% stated that the
      children had some oral habit, with pacifier sucking being the most frequent
      (45.6%). Although the majority (97.1%) of the parents or caregivers admitted
      being aware that these habits could be detrimental to teeth, 70.2% of the
      respondents had already offered a pacifier to children, in most cases to calm
      them (61.8%). There was a statistically significant association between offering
      a pacifier to a child and knowledge about the relationship of the existence of
      non-nutritive habits and the occurrence of malocclusion (p <0.0001 and Chi-square
      = 60.123). The conclusion is that the prevalence of oral habits of the population
      is high and, despite the majority of parents knowing that pacifier sucking can
      cause damage to oral health, they offer them to calm the child. 

PMID- 24863832
TI  - [The causes of physical disability in municipalities of the northeast of Brazil
      and an estimate of costs of specialized services].
AB  - The population of the northeast of Brazil is characterized by high rates of
      endogamy and disabilities. An epidemiological cross-sectional study using the
      informant method was conducted in eight communities in the hinterlands of Paraiba
      to describe genetic and acquired diseases that cause disabilities and to estimate
      the costs of specialized services such as physiotherapy and the acquisition of
      technological assistential equipment. From a population of 48,499 inhabitants,
      338 individuals were screened and 123 (0.34%) were clinically, genetically and
      functionally assessed by a multidisciplinary team of specialists. Genetic factors
      were responsible for 58.5% of the disabilities, with some clusters of prevalent
      diseases being found within the sampled communities, namely progressive spinal
      muscular atrophy, spinocerebellar ataxia, muscular dystrophy and Spoan syndrome.
      The socioeconomic profile and the demand for rehabilitation services and
      technological assistance highlight the need to introduce and implement specific
      public health policies in these communities. 

PMID- 24863833
TI  - [The therapeutic community for recuperation from addiction to alcohol and other
      drugs in Brasil: in line with or running counter to psychiatric reform?].
AB  - In the second half of the last century a revolutionary movement began in the
      world mental health scenario, namely Psychiatric Reform. At the same juncture,
      the concept was also put forward for Therapeutic Communities, which would later
      become the tried and tested model for treatment of addiction to alcohol and other
      drugs. However, due to the alarming increase of this problem in Brazil, as well
      as the absence of public policies to address the problem, there was an
      indiscriminate proliferation of chemical dependency internment locations that,
      despite calling themselves Therapeutic Communities, in no way resembled the
      initial model proposed. These places featured inhuman and iatrogenic practices,
      very similar to those criticized by the Psychiatric Reform movement, which
      consequently discredited the Therapeutic Community model. This article seeks to
      demonstrate, through bibliographic research, how the conceptual and
      methodological bases of Psychiatric Reform closely resemble the Therapeutic
      Communities movement, having appeared at the same time and for the same reason,
      and how the lack of control and regulation of chemical dependency internment
      locations in Brazil has contributed to the current disrepute of this model. 

PMID- 24863835
TI  - [The judicialization of health in the Federal District of Brazil].
AB  - This paper seeks to analyze the Judiciary's approach with respect to demands for
      the judicialization of the right to health by means of a case study of civil
      lawsuits for access to health care in Brazil's Federal District. Judicialization
      of the right to health signifies the judicialization of various of the health
      services provided. This is a descriptive and exploratory case study that covers
      the Federal District and uses mixed techniques to gather and analyze data. This
      study analyzed 385 lawsuits (87% of the total number of cases of judicialization
      of health for the period from 2005 to 2010 that reached the Appellate court). The
      results indicate that the most judicialized service is access to intensive care
      unit, followed by drugs and health care. Almost all lawsuits are filed by public
      defenders, with medical prescriptions and recommendations from the public health
      service. The results of this study challenge some dominant themes in the national
      debate, particularly the claim that judicialization is a phenomenon of the elites
      and that the services judicialized are drugs. The study does not seek to make
      generalizations, but highlights the fact that the phenomenon of judicialization
      of health has different aspects encompassed under the same concept. 

PMID- 24863834
TI  - [Factors associated with tooth loss among adults in rural areas in the state of
      Pernambuco, Brazil].
AB  - The scope of this study was to estimate the prevalence of tooth loss and
      associated factors among Brazilian adults aged 20 to 59 years in rural areas in
      the state Pernambuco, Brazil. A cross-sectional study was conducted on a random
      sample of 568 participants. The number of lost teeth (d" 12 and > 12) was the
      outcome investigated. The independent variables were as follows: sociodemographic
      characteristics, subjective oral health conditions, impact of oral health on
      quality of life using the short version of the Oral Health Impact Profile (OHIP
      14), and the use of dental services. Crude and adjusted prevalence ratios were
      estimated using a Poisson regression model. The prevalence of subjects with at
      least one tooth lost was 91.4%. Tooth loss was strongly associated with age
      group, self-perceived oral health and oral health impact on quality of life. The
      high prevalence of tooth loss among Brazilian adults in rural areas shows a need
      for a reorientation of public dental services aimed at this population group. 

PMID- 24863836
TI  - [Cost of illness attributable to environmental factors in the city of Manaus,
      state of Amazonas, Brazil].
AB  - The study estimated the cost of illness attributable to environmental factors in
      the city of Manaus between the years 1998 to 2009. The causes of hospitalization
      were grouped based on studies of the Global Burden of Disease and Comparative
      Risk Assessment of the World Health Organization. The value was estimated by the
      sum of (i) hospital spending on treatment of diseases directly attributable to
      environmental factors, and (ii) the costs of lost workdays resulting from the
      stay in hospital estimated on the basis of the average earnings of Manaus
      workers. The data were further calibrated taking into account the coverage of the
      population with private health insurance. The cost of illness, considering the
      values corrected by the General Market Price Index for the year 2009 was
      estimated at R$ 286,852,666.97, of which cardiovascular disease, respiratory
      infections of the lower airways and diarrheal diseases are responsible for 78.6%
      of these values. Of the fractions attributable to environmental factors,
      cardiovascular diseases account for 16% (CI: 7-23%), respiratory infections and
      respiratory infections of the lower airways for 41% (CI: 32-47%), and diarrhea
      for 94% (CI: 84-98%) of the global burden of disease. 

PMID- 24863837
TI  - [Pharmaceutical care and attention suspended: compromise-formations between
      pharmacy and psychoanalysis [corrected]].
AB  - This paper presents an interdisciplinary overview of the rational use of medicine
      from a metapsychological standpoint. The need to reinstate the activity of the
      pharmaceutical professionals vis-a-vis their patients through pharmaceutical care
      demands the intervention of new know-how that can ensure a revitalization of this
      human relationship. In this sense, by means of a compilation of passages from the
      works of Freud, some of the most important metapsychological concepts were
      presented: psychic apparatus, evenly hovering attention and commitment
      formations. These concepts were then presented as an applicable theoretical tool
      for qualitative analysis in pharmaceutical care, though especially for
      participant observation. Thus, the main objective was to provide new tools for
      the pharmacists in terms of listening and receptivity, which can enhance their
      professional routine regarding the relationship with their patients, as well as
      in the gathering and interpretation of qualitative data concerning human issues
      involving pharmaceutical care. 

PMID- 24863838
TI  - [Vulnerability in adolescent health: contemporary issues].
AB  - The objective of this exploratory study with a qualitative approach was to
      analyze how adolescents perceive reality in terms of vulnerability in respect to
      health. A total of 17 semi-structured interviews were staged with adolescents
      from two elementary-middle (k-8) schools in a city in the interior of Sao Paulo,
      Brazil. Content analysis was used to interpret the data, from which three
      thematic nuclei emerged. The results revealed that the adolescents understand the
      complex interaction between individual predisposition and health vulnerability,
      as well as the issues related to social structure, which contributes to
      strengthening the concept of vulnerability based on individual, social and
      programmatic logic. It was established that public policies, prevention and care
      provided during adolescence should not be guided by a single reference point, but
      instead by the plurality of the adolescent individuals concerning vulnerability
      in their dimensions, which should be acknowledged in order to break with the idea
      of the universality of the process of becoming an adolescent. 

PMID- 24863839
TI  - [Factors associated with use of oral health services: a population-based study in
      municipalities of the state of Maranhao, Brazil].
AB  - The scope of this study was to evaluate the use of oral health services (OHS) and
      related factors in municipalities with more than 100,000 inhabitants in Maranhao,
      Brazil. It was a population-based sample including 1214 children and 1059 adults.
      Prevalence ratios (PR) were estimated by hierarchical Poisson regression in
      accordance with Andersen's theoretical model. Over 91% of children and 71.9% of
      adults had not used the OHS in the six months prior to the interview. Of those
      who did, 48.5% were attended in the Unified Health System (SUS). Preventive were
      more frequent than curative procedures. In children and adults, predisposing,
      facilitating and need-based factors explained the use of OHS. Children aged >2
      years (PR=5.29), with greater schooling of the head of the household (PR=2.37),
      e"6 prenatal visits (PR=1.69) and dental treatment needs (PR=9.54) were
      associated with greater use of the OHS. In adults, use was associated with
      greater schooling (PR=2.26), economic class A/B (PR=1.38), self-perceived health
      as good/very good (PR=1.72) and need for treatment (PR=18.25). The use of the OHS
      is neither universal nor equitable and there are deficiencies in comprehensive
      care, as few people use the more complex services. Fewer prenatal visits appear
      to be a predictor of non-use of the OHS by children. 

PMID- 24863840
TI  - [Food security, growth and vitamin A, hemoglobin and zinc levels of preschool
      children in the northeast of Brazil].
AB  - This study sought to examine the association between the food (in)security and
      nutritional status of preschool children attended in daycare centers. Food
      security was assessed using the Brazilian Food Insecurity Scale. The nutritional
      status was evaluated using the weight/height, weight/age, height/age, hemoglobin,
      serum retinol and serum zinc status. The prevalence of stunting (6.2%),
      overweight (3.1%), underweight (2.1%), vitamin A deficiency (24.4%), anemia
      (15.5%), and zinc deficiency (15%) was established. Food insecurity was found in
      64.4% of the families, predominantly in its mild form (32.6%). This study
      concludes that food insecurity as measured by the EBIA was not associated with Z
      score growth or with vitamin A, hemoglobin and zinc biochemical concentrations. 

PMID- 24863842
TI  - Clotrimazole as a pharmaceutical: past, present and future.
AB  - Clotrimazole is a broad-spectrum antimycotic drug mainly used for the treatment
      of Candida albicans and other fungal infections. A synthetic, azole antimycotic,
      clotrimazole is widely used as a topical treatment for tinea pedis (athlete's
      foot), as well as vulvovaginal and oropharyngeal candidiasis. It displays
      fungistatic antimycotic activity by targeting the biosynthesis of ergosterol,
      thereby inhibiting fungal growth. As well as its antimycotic activity,
      clotrimazole has become a drug of interest against several other diseases such as
      sickle cell disease, malaria and some cancers. It has also been combined with
      other molecules, such as the metals, to produce clotrimazole complexes that show
      improved pharmacological efficacy. Moreover, several new, modified-release
      pharmaceutical formulations are also undergoing development. Clotrimazole is a
      very well-tolerated product with few side effects, although there is some drug
      resistance appearing among immunocompromised patients. Here, we review the
      pharmaceutical chemistry, application and pharmacology of clotrimazole and
      discuss future prospects for its further development as a chemotherapeutic agent.

PMID- 24863843
TI  - Arterial supply of the upper cranial nerves: a comprehensive review.
AB  - The arterial supply to the upper cranial nerves is derived from a complex network
      of branches derived from the anterior and posterior cerebral circulations. We
      performed a comprehensive literature review of the arterial supply of the upper
      cranial nerves with an emphasis on clinical considerations. Arteries coursing in
      close proximity to the cranial nerves regularly give rise to small vessels that
      supply the nerve. Knowledge of the arteries supplying the cranial nerves is of
      particular importance during surgical approaches to the skull base.

PMID- 24863844
TI  - Synthesis and antifilarial activity of chalcone-thiazole derivatives against a
      human lymphatic filarial parasite, Brugia malayi.
AB  - Here we report the synthesis of novel chalcone-thiazole compounds and their
      antifilarial activity. The antifilarial properties of these hybrids were assessed
      against microfilariae as well as adult worms of Brugia malayi. Among all the
      synthesized compounds, only two compounds, namely 4g and 4n were identified to be
      promising in vitro. These active compounds were tested in B. malayi-jird
      (Meriones unguiculatus) and B. malayi-Mastomys coucha models. Compound 4n showed
      100% embryostatic effect and 49% macrofilaricidal in jirds and M. coucha models,
      respectively. This study provides a new structural clue for the development of
      novel antifilarial lead molecules. 

PMID- 24863845
TI  - Essential function for PDLIM2 in cell polarization in three-dimensional cultures
      by feedback regulation of the beta1-integrin-RhoA signaling axis.
AB  - PDLIM2 is a cytoskeletal and nuclear PDZ-LIM domain protein that regulates the
      stability of Nuclear Factor kappa-B (NFkappaB) and other transcription factors,
      and is required for polarized cell migration. PDLIM2 expression is suppressed by
      methylation in different cancers, but is strongly expressed in invasive breast
      cancer cells that have undergone an Epithelial Mesenchymal Transition (EMT).
      PDLIM2 is also expressed in non-transformed breast myoepithelial MCF10A cells and
      here we asked whether it is important for maintaining the polarized, epithelial
      phenotype of these cells. Suppression of PDLIM2 in MCF10A cells was sufficient to
      disrupt cell polarization and acini formation with increased proliferation and
      reduced apoptosis in the luminal space compared to control acini with hollow
      lumina. Spheroids with suppressed PDLIM2 exhibited increased expression of cell
      cell and cell-matrix adhesion proteins including beta 1 (beta1) integrin.
      Interestingly, levels of the Insulin-like growth factor 1 receptor (IGF-1 R) and
      Receptor of activated protein kinase C 1 (RACK1), which scaffolds IGF-1R to beta1
      integrin, were also increased, indicating a transformed phenotype. Focal Adhesion
      Kinase (FAK) and cofilin phosphorylation, and RhoA Guanosine Triphosphatase
      (GTPase) activity were all enhanced in these spheroids compared to control acini.
      Importantly, inhibition of either FAK or Rho Kinase (ROCK) was sufficient to
      rescue the polarity defect. We conclude that PDLIM2 expression is essential for
      feedback regulation of the beta1-integrin-RhoA signalling axis and integration of
      cellular microenvironment signals with gene expression to control the polarity of
      breast epithelial acini structures. This is a mechanism by which PDLIM2 could
      mediate tumour suppression in breast epithelium. 

PMID- 24863846
TI  - Regulatory T cell subsets in children with systemic lupus erythematosus.
AB  - The aim of this work was to quantify CD4(+)CD25(+)Foxp3(+) T cells (Tregs) in
      Egyptian children with SLE and to correlate these findings with their disease
      activity scores and drug therapy. We enrolled 37 Egyptian children with active
      SLE. Disease activity was assessed by measuring serum levels of anti-dsDNA
      antibody and by the SLEDAI scores. Twenty healthy children were also enrolled as
      normal controls. The CD4+CD25+, CD4+CD25(bright), and CD4+CD25(dim) cells in
      patients were significantly increased in comparison to controls. There was no
      significant difference in the Foxp3 gated on CD4+CD25(bright) and CD4+CD25(dim),
      but there was a significant increase when gated on CD4+CD25- and whole CD4+ cells
      in patients than controls. There was no significant difference among patients
      with different degrees of activity on different lines of treatments and their
      outcomes as regards all studied values. There was no significant correlation
      between SLEDAI score and any of the studied parameters except for a significant
      negative correlation with gated lymphocytes. There is increased expression of
      Foxp3 in CD4+ T cells mostly CD25- in Egyptian children with active SLE under
      corticosteroid treatment regardless of disease activity. 

PMID- 24863847
TI  - Microscopic polyangiitis associated with pulmonary fibrosis.
AB  - Microscopic polyangiitis (MPA) is a systemic necrotizing vasculitis characterised
      by inflammation of the small blood vessels, the absence of granulommas on
      histopathological specimens, with few or no immune deposits and the presence of
      circulating anti-neutrophil cytoplasmic antibodies (ANCAs). The classic pulmonary
      manifestation is diffuse alveolar haemorrhage (DAH), but its association with
      pulmonary fibrosis (PF) has been increasingly reported and may be the first
      manifestation of MPA. Our aim was to evaluate MPA patients with PF and compare
      their characteristics and evolution to those of MPA patients without PF. We
      conducted a retrospective review of MPA patients followed in our hospital over a
      15-year period. They were divided into two subgroups, with PF (MPA-PF) and
      without PF (MPA-non PF), and their clinical and functional features were
      compared. Nine of the 28 patients were classified as MPA-PF (32%). This subgroup
      showed significantly more respiratory symptoms and higher mortality than MPA-non
      PF subgroup. The most frequent chest computed tomographic pattern of PF was usual
      interstitial pneumonia. PF preceded other manifestations of vasculitis in five
      patients and occurred simultaneously in the remaining four. During the follow-up
      period, four deaths were reported in the MPA-PF subgroup. No deaths were
      registered in the MPA-non PF subgroup. We found a high prevalence of MPA-PF
      patients (32%), most of whom had a poor outcome and PF was often the first
      manifestation of the disease.

PMID- 24863848
TI  - Lucio's phenomenon: report of five cases.
AB  - The different clinical forms of leprosy are mainly related to the variety of
      immunological responses to the infection. Several forms of lepromatous leprosy
      are recognized, including macular, nodular, and diffuse. Lucio's phenomenon is a
      rare but distinctive skin eruption seen in patients with diffuse lepromatous
      leprosy. The diffuse lesions of Lucio's phenomenon have a predilection for the
      extremities, can include nodules, and heal with atrophic stellate scars;
      histologically, a necrotizing vasculitis accompanied by a nonspecific
      inflammatory reaction may be seen. Because of its rarity and similarity with some
      manifestations of the rheumatic disease and other causes of vasculitis, Lucio's
      phenomenon may not be easily recognized, especially in non-endemic countries,
      which leads to confusing diagnosis and loss of time for treatment. We report five
      patients with vasculitis caused by Lucio's phenomenon. 

PMID- 24863849
TI  - In vivo imaging of membrane type-1 matrix metalloproteinase with a novel
      activatable near-infrared fluorescence probe.
AB  - Membrane type-1 matrix metalloproteinase (MT1-MMP) is a protease activating MMP-2
      that mediates cleavage of extracellular matrix components and plays pivotal roles
      in tumor migration, invasion and metastasis. Because in vivo noninvasive imaging
      of MT1-MMP would be useful for tumor diagnosis, we developed a novel near
      infrared (NIR) fluorescence probe that can be activated following interaction
      with MT1-MMP in vivo. MT1-hIC7L is an activatable fluorescence probe comprised of
      anti-MT1-MMP monoclonal antibodies conjugated to self-assembling polymer micelles
      that encapsulate NIR dyes (IC7-1, lambdaem : 858 nm) at concentrations sufficient
      to cause fluorescence self-quenching. In aqueous buffer, MT1-hIC7L fluorescence
      was suppressed to background levels and increased approximately 35.5-fold in the
      presence of detergent. Cellular uptake experiments revealed that in MT1-MMP
      positive C6 glioma cells, MT1-hIC7L showed significantly higher fluorescence that
      increased with time as compared to hIC7L, a negative control probe lacking the
      anti-MT1-MMP monoclonal antibody. In MT1-MMP negative MCF-7 breast adenocarcinoma
      cells, both MT1-hIC7L and hIC7L showed no obvious fluorescence. In addition, the
      fluorescence intensity of C6 cells treated with MT1-hIC7L was suppressed by pre
      treatment with an MT1-MMP endocytosis inhibitor (P < 0.05). In vivo optical
      imaging using probes intravenously administered to tumor-bearing mice showed that
      MT1-hIC7L specifically visualized C6 tumors (tumor-to-background ratios: 3.8 +/-
      0.3 [MT1-hIC7L] vs 3.1 +/- 0.2 [hIC7L] 48 h after administration, P < 0.05),
      while the probes showed similarly low fluorescence in MCF-7 tumors. Together,
      these results show that MT1-hIC7L would be a potential activatable NIR probe for
      specifically detecting MT1-MMP-expressing tumors.

PMID- 24863850
TI  - A prospective randomized study of bicompartmental vs. total knee arthroplasty
      with functional testing and short term outcome.
AB  - The purpose of this study was to compare 50 bicompartmental knee arthroplasty
      (BKA) and total knee arthroplasty (TKA) cases, particularly in restoring knee
      function. Patients were between 30 and 65 years old, with a BMI under 35, and had
      osteoarthritis in the medial and patellofemoral compartments. Knee Society
      scores, Oxford questionnaires, radiographs, and functional tests were performed
      preoperatively, and at 1, 4, 12, and 24 months postoperatively. Functional
      testing included gait analysis, stair climbing, lunging, and sit-to-stand
      analysis. Both groups achieved equivalent Knee Society scores (2 year mean 93.6
      vs. 92.6, P=0.43) and Oxford scores (2-year mean 43 vs. 41, P=0.35). Functional
      testing showed significant improvement. Two years postoperatively the BKA and TKA
      groups achieved equivalent results in clinical scores and functional testing.

PMID- 24863851
TI  - Response to letter to the editor by William H. Harris.

PMID- 24863852
TI  - Accuracy of electronic apex locators in primary teeth: a meta-analysis.
AB  - AIM: To conduct a meta-analysis on the accuracy of electronic apex locators
      (EALs) in determining working length in human primary teeth. METHODOLOGY: An
      electronic literature search was conducted using a combination of the terms
      'primary teeth', 'root canal length' and 'electronic apex locators'. Additional
      eligible articles were identified using a manual search. The full texts of
      identified articles were screened according to inclusion criteria. RESULTS:
      Overall, 19 studies met the inclusion criteria and were subjected to further data
      extraction. Meta-analysis of studies that reported mean lengths and difference in
      mean lengths between EAL and actual root canal length (ARCL) revealed a
      significant difference (P = 0.015) between the two readings whilst those studies
      that evaluated intraclass correlation (ICC) suggested a high correlation (P <
      0.0001) between the EAL and ARCL readings. A subgroup analysis revealed that the
      presence of root resorption did not affect the accuracy of EALs (P = 0.567).
      CONCLUSION: Electronic apex locators offer an acceptable level of accuracy in the
      measurement of root canal length in primary teeth.

PMID- 24863853
TI  - Unlocking the N(2)  selectivity of benzotriazoles: regiodivergent and highly
      selective coupling of benzotriazoles with allenes.
AB  - The rhodium-catalyzed, highly N(2) - and N(1) -selective coupling of
      benzotriazoles with allenes is reported. The exceptionally high N(2) and N(1)
      selectivities were achieved by using a rhodium(I)/DPEphos and
      rhodium(I)/JoSPOphos catalyst, respectively. This method permits the atom
      economic synthesis of valuable branched N(2) - and N(1) -allylated benzotriazole
      derivatives and allows for preliminary studies of their reactivity. 

PMID- 24863854
TI  - Use of a combination formulation of bismuth, metronidazole and tetracycline with
      omeprazole as a rescue therapy for eradication of Helicobacter pylori.
AB  - BACKGROUND: Helicobacter pylori infection occurs in children and adults
      worldwide. Standard triple therapy of omeprazole, amoxicillin and clarithromycin
      (OAC) may not be optimal. AIM: To evaluate quadruple therapy with bismuth
      subcitrate potassium, metronidazole and tetracycline hydrochloride, given with
      omeprazole in H. pylori infected subjects who failed previous OAC eradication
      therapy. METHODS: This was a multicenter, open-label, single-arm, multinational
      study. Helicobacter pylori-positive subjects who had failed >=1 previous course
      of OAC therapy with or without up to three supplemental treatments in the
      previous year. Subjects were treated for 10 days with a combination formulation
      containing bismuth subcitrate potassium 140 mg, tetracycline hydrochloride 125
      mg, and metronidazole 125 mg, three capsules four times daily (q.d.s.), and
      omeprazole 20 mg twice daily (b.d.). The primary endpoint was H. pylori
      eradication rate defined as one negative (13) C-urea breath test >=28 days post
      treatment. RESULTS: Helicobacter pylori eradication rates ranged from 93.2% to
      93.8% in the intent-to-treat population (n = 49), and from 94.7% to 95.0% in the
      PP population (n = 40). No clinically meaningful differences were observed when
      analysed by country. Metronidazole resistance was observed in 16/49 (32.7%)
      subjects and clarithromycin resistance in 31/49 (63.3%) subjects. Thirty-three
      subjects (67.3%) reported 87 adverse events, and only one (2%) discontinued the
      study for an adverse event. CONCLUSIONS: A quadruple regimen of bismuth,
      metronidazole and tetracycline plus omeprazole produces a high eradication rate
      in subjects previously failing H. pylori eradication regimens. This bismuth-based
      regimen offers an effective option as rescue therapy.

PMID- 24863855
TI  - High-probability features of primary aldosteronism may obviate the need for
      confirmatory testing without increasing false-positive diagnoses.
AB  - This retrospective review examined all primary aldosteronism (PA) adrenal vein
      sampling (AVS), diagnoses, and outcomes from an endocrine hypertension unit where
      confirmatory testing was abandoned in 2005 to determine the potential rate of
      false-positive diagnoses. Patients with outcome-verified PA (surgical patients)
      were compared with patients with high-probability PA (nonsurgical but high
      aldosterone-renin ratio, imaging abnormalities, and/or hypokalemia) or possible
      PA (nonsurgical, no features besides mild elevation of aldosterone-renin ratio, a
      potential false diagnosis of PA). Of 83 patients, 58% had unilateral PA and 42%
      had bilateral aldosteronism. Less than 3% of the cohort showed bilateral
      aldosteronism without hypokalemia or computed tomographic findings, potentially
      representing the false-positive PA diagnosis rate with omission of confirmatory
      tests in this population. In a hypertension referral unit enriched in high
      probability PA cases and where high AVS success is achieved, omission of a PA
      confirmatory test yields a high rate of surgical diagnosis with few potential
      false-positive diagnoses. 

PMID- 24863856
TI  - Author's response to the letter to the editor.

PMID- 24863857
TI  - [Inequalities in physical inactivity according educational level in Spain, 1987
      and 2007].
AB  - OBJECTIVE: To compare the magnitude of inequalities in the frequency of physical
      inactivity in Spain in 1987 and 2007, and assess whether the magnitude of
      inequality varies depending on the wealth of the area of residence. DESIGN:
      Descriptive cross-sectional study, national scope. PARTICIPANTS: Data from the
      National Health Survey, 1987 and 2007, adult population between 25-64 years:
      30,000 individuals (1987) and 29,478 (2006/7). MAIN MEASUREMENTS: Main outcomes
      variable, leisure-time physical inactivity; exposure factor, educational level.
      An analysis was made of the prevalence and association using odds ratio (OR).
      Adjustment for socioeconomic variables: age, marital status, employment status,
      social class of head of household, and household income. RESULTS: Physical
      inactivity prevalence decreased in the two decades. There were more than three
      times more inactive males among those with primary education or less, compared to
      those with university studies. The magnitude of inequalities has increased in
      time: in a 45-64 years old man with primary school education: OR 2.43 (1.91-3.09)
      in 1987, to OR 2.77 (2.17-3.54) in 2007, adjusted for all socioeconomic
      variables. CONCLUSIONS: The prevalence of physical inactivity decreased between
      1987 and 2007, and the largest decreases were in individuals with university
      studies. The gap in the differences in prevalence and OR of leisure-time physical
      inactivity has increased over time. It's necessary to contribute, with health
      education strategies and equity promotion are needed to help reduce the
      inequalities in risk behaviors.

PMID- 24863858
TI  - Is physiotherapy self-referral with telephone triage viable, cost-effective and
      beneficial to musculoskeletal outpatients in a primary care setting?
AB  - OBJECTIVE: The aim of the present study was to establish if physiotherapy self
      referral (SR) is viable, cost effective and beneficial to musculoskeletal
      outpatients in a primary care setting. SETTING: In an urban National Health
      Service (NHS) primary care physiotherapy service, waiting times, attendance rates
      and treatment ratios (thus, episode-of-care costs) were deemed unsustainable. The
      introduction of 'Any Qualified Provider' is imminent and will drive NHS
      physiotherapy services to compete directly with private counterparts. Current
      literature, healthcare policy and the Chartered Society of Physiotherapy strongly
      advocate SR to promote value for money and improve the patient experience.
      DESIGN: A repeated measure prospective cohort study introduced an SR pathway
      parallel to existing general practice (GP) referrals and compared costs,
      attendance and data relating to the patient experience across groups. RESULTS: SR
      referral groups were found to have a higher proportion of female patients
      presenting with acute conditions. Cost minimization analysis indicated an average
      32.3% reduction in episode-of-care cost with an SR-initiated intervention. An
      estimated cost minimization of between L84,387.80 and L124,472.06 was calculated
      if SR were to be expanded service-wide. SR referral reduced waiting times and
      improved patient satisfaction relating to waiting times and communication
      compared with traditional pathways. CONCLUSIONS: The results of the present study
      showed that the introduction of the described SR pathway was feasible, cost
      effective and offered comparable care. Certain aspects of the SR patient
      experience compared more favourably than those studied in traditional GP referral
      routes. They also added to an existing body of evidence supporting SR with a
      variety of administrative processes in various socioeconomic settings.

PMID- 24863860
TI  - Clinical correlates of distorted auditory perception in first-episode psychosis.
AB  - AIM: Auditory hallucinations are hypothesized to be based in distorted sensory
      perceptions, with increasingly distorted perceptions of reality possibly
      prompting the first psychotic phase of schizophrenia spectrum disorders. Our goal
      was to examine the association between distorted auditory perceptions and
      psychotic symptomatology, social functioning and quality of life among
      individuals with first-episode psychosis. METHODS: Forty individuals with first
      episode psychosis completed assessments of distorted auditory perception,
      psychotic symptomatology, social functioning and quality of life. RESULTS: Both
      negative (greater symptomatology) and positive clinical correlates (better
      quality of life) were associated with greater distorted auditory perceptions.
      CONCLUSIONS: Our findings suggest that distorted auditory perceptions are
      associated with both positive and negative clinical correlates among individuals
      with first-episode psychosis. These results highlight the potential clinical
      importance of balancing the goal of symptomatic reduction with the need to
      maintain healthy coping strategies that may be biologically and psychologically
      entwined with the symptoms of psychosis, themselves.

PMID- 24863861
TI  - Screening for HLA antibodies in plateletpheresis donors with a history of
      transfusion or pregnancy.
AB  - BACKGROUND: Transfusion-related acute lung injury (TRALI) is known as a life
      threatening complication of transfusion. HLA and HNA antibodies have been
      associated with the immune pathway of TRALI. Since donors with a history of
      transfusion and/or pregnancy are presumed to have an increased risk of carrying
      such antibodies, we investigated the association of a history of transfusion or
      pregnancy with the occurrence of HLA alloimmunization in our donor population.
      STUDY DESIGN AND METHODS: A total of 1018 female plateletpheresis donors and male
      plateletpheresis donors with a history of transfusion were enrolled in the study.
      Included donors were systematically screened, using Luminex technology, for anti
      HLA Class I and II. The association of donor history with HLA alloimmunization
      status was analyzed. RESULTS: The overall alloimmunization rate was 20.2%. In
      0.0% of the nulliparous transfused female donors and in 1.3% of the transfused
      male donors, anti-HLA were detected. Thirty-one percent of the parous women
      versus 4.2% of the nulliparous women screened positive for anti-HLA. The rate of
      HLA alloimmunization increased with parity. CONCLUSION: Our data indicate that a
      history of transfusion is a minor risk factor for immunization against HLA
      antigens. In contrast, former pregnancies constitute a major risk factor for the
      development of HLA antibodies. Since HLA alloimmunization rate increases with
      parity, TRALI risk reduction measures should focus on this particular donor
      population. Repeated testing of female plateletpheresis donors after each
      pregnancy is implemented in our blood service.

PMID- 24863862
TI  - Nanostructured WO3 /BiVO4 photoanodes for efficient photoelectrochemical water
      splitting.
AB  - Nanostructured photoanodes based on well-separated and vertically oriented WO3
      nanorods capped with extremely thin BiVO4 absorber layers are fabricated by the
      combination of Glancing Angle Deposition and normal physical sputtering
      techniques. The optimized WO3 -NRs/BiVO4 photoanode modified with Co-Pi oxygen
      evolution co-catalyst shows remarkably stable photocurrents of 3.2 and 5.1
      mA/cm(2) at 1.23 V versus a reversible hydrogen electrode in a stable Na2 SO4
      electrolyte under simulated solar light at the standard 1 Sun and concentrated 2
      Suns illumination, respectively. The photocurrent enhancement is attributed to
      the faster charge separation in the electronically thin BiVO4 layer and
      significantly reduced charge recombination. The enhanced light trapping in the
      nanostructured WO3 -NRs/BiVO4 photoanode effectively increases the optical
      thickness of the BiVO4 layer and results in efficient absorption of the incident
      light. 

PMID- 24863863
TI  - Capacities for theory of mind, metacognition, and neurocognitive function are
      independently related to emotional recognition in schizophrenia.
AB  - While many with schizophrenia spectrum disorders experience difficulties
      understanding the feelings of others, little is known about the psychological
      antecedents of these deficits. To explore these issues we examined whether
      deficits in mental state decoding, mental state reasoning and metacognitive
      capacity predict performance on an emotion recognition task. Participants were
      115 adults with a schizophrenia spectrum disorder and 58 adults with substance
      use disorders but no history of a diagnosis of psychosis who completed the Eyes
      and Hinting Test. Metacognitive capacity was assessed using the Metacognitive
      Assessment Scale Abbreviated and emotion recognition was assessed using the Bell
      Lysaker Emotion Recognition Test. Results revealed that the schizophrenia
      patients performed more poorly than controls on tests of emotion recognition,
      mental state decoding, mental state reasoning and metacognition. Lesser
      capacities for mental state decoding, mental state reasoning and metacognition
      were all uniquely related emotion recognition within the schizophrenia group even
      after controlling for neurocognition and symptoms in a stepwise multiple
      regression. Results suggest that deficits in emotion recognition in schizophrenia
      may partly result from a combination of impairments in the ability to judge the
      cognitive and affective states of others and difficulties forming complex
      representations of self and others. 

PMID- 24863864
TI  - Pharmacological and non-pharmacological interventions to improve cognitive
      dysfunction and functional ability in clinical depression--a systematic review.
AB  - Cognitive dysfunction is of clinical significance and exerts longstanding
      implication on patients' function. Pharmacological and non-pharmacological
      treatments of cognitive dysfunction are emerging. This review evaluates
      pharmacological and non-pharmacological treatments of cognitive impairment
      primarily in the domains of memory, attention, processing speed and executive
      function in clinical depression. A total of 35 studies were retrieved from
      Pubmed, PsycInfo and Scopus after applying inclusion and exclusion criteria.
      Results show that various classes of antidepressants exert improving effects on
      cognitive function across several cognitive domains. Specifically, studies
      suggest that SSRIs, the SSRE tianeptine, the SNRI duloxetine, vortioxetine and
      other antidepressants such as bupropion and moclobemide may exert certain
      improving effects on cognitive function in depression, such as in learning and
      memory and executive function. Class-specific cognitive domains or specific dose
      response relationships were not identified yet. The few non-pharmacological
      studies conducted employing cognitive orientated treatments and cognitive
      remediation therapy show promising results for the improvement of cognitive
      impairment in depression. However, several methodological constraints of studies
      limit generalizability of the results and caution the interpretation. Future
      direction should consider the development of a neuropsychological consensus
      cognitive battery to support the discovery, clinical assessment, comparison of
      studies and registration of new agents in clinical depression. 

PMID- 24863865
TI  - Molecular genetic studies of ADHD and its candidate genes: a review.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is a common childhood-onset
      psychiatric disorder with high heritability. In recent years, numerous molecular
      genetic studies have been published to investigate susceptibility loci for ADHD.
      These results brought valuable candidates for further research, but they also
      presented great challenge for profound understanding of genetic data and general
      patterns of current molecular genetic studies of ADHD since they are scattered
      and heterogeneous. In this review, we presented a retrospective review of more
      than 300 molecular genetic studies for ADHD from two aspects: (1) the main
      achievements of various studies were summarized, including linkage studies,
      candidate-gene association studies, genome-wide association studies and genome
      wide copy number variation studies, with a special focus on general patterns of
      study design and common sample features; (2) candidate genes for ADHD have been
      systematically evaluated in three ways for better utilization. The thorough
      summary of the achievements from various studies will provide an overview of the
      research status of molecular genetics studies for ADHD. Meanwhile, the analysis
      of general patterns and sample characteristics on the basis of these studies, as
      well as the integrative review of candidate ADHD genes, will propose new clues
      and directions for future experiment design. 

PMID- 24863866
TI  - The heritability of mental health and wellbeing defined using COMPAS-W, a new
      composite measure of wellbeing.
AB  - Mental health is not simply the absence of mental illness; rather it is a
      distinct entity representing wellness. Models of wellbeing have been proposed
      that emphasize components of subjective wellbeing, psychological wellbeing, or a
      combination of both. A new 26-item scale of wellbeing (COMPAS-W) was developed in
      a cohort of 1669 healthy adult twins (18-61 years). The scale was derived using
      factor analysis of multiple scales of complementary constructs and confirmed
      using tests of reliability and convergent validity. Bivariate genetic modeling
      confirmed its heritability. From an original 89 items we identified six
      independent subcomponents that contributed to wellbeing. The COMPAS-W scale and
      its subcomponents showed construct validity against psychological and physical
      health behaviors, high internal consistency (average r=0.71, Wellbeing r=0.84),
      and 12-month test-retest reliability (average r=0.62, Wellbeing r=0.82). There
      was a moderate contribution of genetics to total Wellbeing (heritability
      h(2)=48%) and its subcomponents: Composure (h(2)=24%), Own-worth (h(2)=42%),
      Mastery (h(2)=40%), Positivity (h(2)=42%), Achievement (h(2)=32%) and
      Satisfaction (h(2)=43%). Multivariate genetic modeling indicated genetic variance
      was correlated across the scales, suggesting common genetic factors contributed
      to Wellbeing and its subcomponents. The COMPAS-W scale provides a validated
      indicator of wellbeing and offers a new tool to quantify mental health. 

PMID- 24863867
TI  - Prospective memory predicts the level of community living skills in
      schizophrenia.
AB  - Schizophrenia patients are known to have prospective memory (PM) deficits. There
      is no robust evidence showing that PM deficits have a major impact on community
      living skills in schizophrenia. The aim of this study was to examine the
      association between PM and community living skills in schizophrenia. Forty-four
      individuals with schizophrenia formed the study sample. Participants'
      psychopathology, prospective and retrospective memory, level of intelligence, and
      community living skills were measured with standardized instruments. In bivariate
      analyses, community living skills overall but not self-care correlated with PM
      total and subscales scores. In multivariate analyses, event-based PM was more
      predictive than time-based PM of the level of community living skills. In
      conclusion, PM has a significant impact on community living skills in
      schizophrenia and attention should be paid to this type of memory disturbance in
      rehabilitation of schizophrenia. 

PMID- 24863868
TI  - Prolonged grief following the recent death of a daughter among mothers who
      experienced distal losses during the Khmer Rouge era: Validity of the prolonged
      grief construct in Cambodia.
AB  - This study addressed the validity of the prolonged grief (PG) construct in a
      Cambodian context. Eighty mothers who lost a young adult daughter stemming from a
      crowd stampede incident during the annual water festival were interviewed at the
      six-month post-loss point along with a control group of similarly aged women who
      were not recently bereaved. Both groups were assessed for PG, PTSD, anxiety, and
      depression symptoms and well as for the number of distal losses experienced
      during the Khmer Rouge (KR) regime - knowing that all the women were old enough
      to have lived through the KR regime. Support for the discriminant validity of PG
      was shown in a factor analysis in which its core symptoms were distinguished from
      anxiety, depression, and PTSD symptoms. Also, support was found for its
      incremental validity as shown in the unique sensitivity of PG in distinguishing
      the two groups when controlling for the other symptoms. Lastly, a positive
      relationship was found between the number of distal deaths experienced during the
      KR regime and PG symptom severity among the group of recently bereaved mothers,
      providing support for the predictive validity of PG. Implications as well as
      study limitations are discussed. 

PMID- 24863869
TI  - Emotion regulation in children and adolescents with autism spectrum disorder.
AB  - Emotion dysregulation is not a formal criterion for the diagnosis of autism
      spectrum disorder (ASD). However, parents and clinicians have long noted the
      importance of emotional problems in individuals with ASD (e.g. tantrums and
      "meltdowns"). In this study, 21 high-functioning children and adolescents with
      ASD and 22 age and gender group-matched typically developing (TD) controls
      completed a Reactivity and Regulation Situation Task. This task assesses
      emotional reactivity and spontaneous use of emotion regulation strategies
      (problem solving, cognitive reappraisal, avoidance, distraction, venting,
      suppression, and relaxation) in the context of age-appropriate ambiguous and
      potentially threatening negative scenarios. After the concept of cognitive
      reappraisal was explained, the scenarios were presented again to participants,
      and they were prompted to use this strategy. Results indicated that individuals
      with ASD exhibited the same level of reactivity to negative stimuli as TD
      participants. Furthermore, youth with ASD had a different emotion regulation
      profile than TD individuals, characterized by a less frequent use of cognitive
      reappraisal and more frequent use of suppression. When prompted to use cognitive
      reappraisal, participants with ASD were less able to implement reappraisal, but
      benefitted from this strategy when they were able to generate a reappraisal.
      Findings from this study suggest that cognitive reappraisal strategies may be
      useful to children and adolescents with ASD. Therefore, the development of
      treatment programs that focus on enhancing the use of adaptive forms of emotion
      regulation might decrease emotional problems and optimize long-term outcomes in
      youth with ASD.

PMID- 24863870
TI  - Modulatory effects of curcumin on redox status, mitochondrial function, and
      caspace-3 expression during atrazin-induced toxicity.
AB  - Atrazin is currently the most widely used herbicide in agriculture with lots of
      adverse effects on human health. Curcumin is a polyphenol known for its
      antioxidant, anti-inflammatory, and anticancer properties. In the present study,
      the protective effect of curcumin on atrazin-intoxicated rats is evaluated.
      Toxicity was induced by oral administration of atrazine (400 mg/kg/day) for 3
      weeks. Curcumin at a dose of 400 mg/kg/day was given simultaneously by oral
      route. Redox status, mitochondrial function, 8-hydroxydeoxyguanosine (8-OHdG)
      level by immunoassay, and caspace-3 expression by immunohistochemistry were
      evaluated. Curcumin showed significant cardiac protection with improvement of
      redox status, mitochondrial function, 8-OHdG level, caspase-3 immunoreactivity,
      and cardiac muscle degeneration. From this current study, it can be concluded
      that administration of curcumin improved atrazine-induced cardiotoxicity through
      its modulatory effect on redox status, mitochondrial function, and caspase-3
      expression.

PMID- 24863871
TI  - Supramolecular assembly of C3 peptidic molecules into helical polymers.
AB  - Self-assembly of C3 discotic molecules bearing dipeptide pendants into helical
      supramolecular polymers is investigated. The dipeptides are constituted from
      glycine and alanine with altered sequence, aiming at modulating the steric
      hindrance and examining the steric effects on the assembly. This steric hindrance
      effect is further illustrated with a dipeptide formed from glycine and valine,
      which carries a much larger isopropyl side unit. Their supramolecular
      polymerization is examined in various organic solvents and at different
      temperatures. The assembly morphology is directly visualized with atomic force
      microscopy. It is found that small changes in the dipeptide motifs in combination
      with solvent structure and the solution concentrations lead to different
      expression of the supramolecular assembly. 

PMID- 24863872
TI  - Investigating hyponatremia, exit-site management and discharge planning.

PMID- 24863873
TI  - Body sodium, potassium and water in peritoneal dialysis-associated hyponatremia.
AB  - OBJECTIVE: This report presents a method quantitatively analyzing abnormalities
      of body water and monovalent cations (sodium plus potassium) in patients on
      peritoneal dialysis (PD) with true hyponatremia. METHODS: It is well known that
      in the face of euglycemia serum sodium concentration is determined by the ratio
      between the sum of total body sodium plus total body potassium on the one hand
      and total body water on the other. We developed balance equations that enabled us
      to calculate excesses or deficits, relative to the state of eunatremia and dry
      weight, in terms of volumes of water and volumes of isotonic solutions of sodium
      plus potassium when patients presented with hyponatremia. We applied this method
      retrospectively to 5 episodes of PD-associated hyponatremia (serum sodium
      concentration 121-130 mEq/L) and compared the findings of the method with those
      of the clinical evaluation of these episodes. RESULTS: Estimates of the new
      method and findings of the clinical evaluation were in agreement in 4 of the 5
      episodes, representing euvolemic hyponatremia (normal total body sodium plus
      potassium along with water excess) in 1 patient, hypovolemic hyponatremia
      (deficit of total body sodium plus potassium along with deficit of total body
      water) in 2 patients, and hypervolemic hyponatremia (excess of total body sodium
      along with larger excess of total body water) in 1 patient. In the 5(th) patient,
      in whom the new method suggested the presence of water excess and a relatively
      small deficit of monovalent cations, the clinical evaluation had failed to detect
      the cation deficit. CONCLUSIONS: Evaluation of imbalances in body water and
      monovalent cations in PD-associated hyponatremia by the method presented in this
      report agrees with the clinical evaluation in most instances and could be used as
      a guide to the treatment of hyponatremia. Prospective studies are needed to test
      the potential clinical applications of this method.

PMID- 24863874
TI  - Effect of implant design and bioactive glass coating on biomechanical properties
      of fiber-reinforced composite implants.
AB  - This study aimed to evaluate the influence of implant design and bioactive glass
      (BAG) coating on the response of bone to fiber-reinforced composite (FRC)
      implants. Three different FRC implant types were manufactured for the study: non
      threaded implants with a BAG coating; threaded implants with a BAG coating; and
      threaded implants with a grit-blasted surface. Thirty-six implants (six implants
      for each group per time point) were installed in the tibiae of six pigs. After an
      implantation period of 4 and 12 wk, the implants were retrieved and prepared for
      micro-computed tomography (micro-CT), push-out testing, and scanning electron
      microscopy analysis. Micro-CT demonstrated that the screw-threads and implant
      structure remained undamaged during the installation. The threaded FRC/BAG
      implants had the highest bone volume after 12 wk of implantation. The push-out
      strengths of the threaded FRC/BAG implants after 4 and 12 wk (463 degrees N and
      676 degrees N, respectively) were significantly higher than those of the threaded
      FRC implants (416 degrees N and 549 degrees N, respectively) and the nonthreaded
      FRC/BAG implants (219 degrees N and 430 degrees N, respectively). Statistically
      significant correlation was found between bone volume and push-out strength
      values. This study showed that osseointegrated FRC implants can withstand the
      static loading up to failure without fracture, and that the addition of BAG
      significantly improves the push-out strength of FRC implants.

PMID- 24863875
TI  - Physical and molecular changes during the storage of gluten-free rice and oat
      bread.
AB  - Gluten-free bread crumb generally firms more rapidly than regular wheat bread
      crumb. We here combined differential scanning calorimetry (DSC), texture
      analysis, and time-domain proton nuclear magnetic resonance (TD (1)H NMR) to
      investigate the mechanisms underlying firming of gluten-free rice and oat bread.
      The molecular mobility of water and biopolymers in flour/water model systems and
      changes thereof after heating and subsequent cooling to room temperature were
      investigated as a basis for underpinning the interpretation of TD (1)H NMR
      profiles of fresh crumb. The proton distributions of wheat and rice flour/water
      model systems were comparable, while that of oat flour/water samples showed less
      resolved peaks and an additional population at higher T2 relaxation times
      representing lipid protons. No significant crumb moisture loss during storage was
      observed for the gluten-free bread loaves. Crumb firming was mainly caused by
      amylopectin retrogradation and water redistribution within bread crumb. DSC,
      texture, and TD (1)H NMR data correlated well and showed that starch
      retrogradation and crumb firming are much more pronounced in rice flour bread
      than in oat flour bread. 

PMID- 24863876
TI  - A report of three cases of pediatric proliferative fasciitis.
AB  - Proliferative fasciitis is a rapidly growing myofibroblastic proliferation that
      more commonly presents in adults as a subcutaneous mass. Cases in children can
      cause diagnostic difficulty, as histological features often differ from classic
      proliferative fasciitis. We present three cases of pediatric proliferative
      fasciitis, in children age 5-7. Case 1 involved the subcutis and resembled
      conventional proliferative fasciitis. The lesion was focally positive for desmin.
      Case 2 involved the subcutis and was more cellular with focal sheet-like areas of
      ganglion-like fibroblasts. Case 3 involved the dermis and subcutis with a
      diffuse, solid sheet-like pattern of ganglion-like myofibroblasts with numerous
      mitotic figures (4 per 10 high power fields), necrosis and foci of acute
      inflammation. This case had a circumscribed pushing border rather than the more
      common infiltrating border seen in proliferative fasciitis. The cells were
      positive for desmin but negative for cytokeratin and had retained SMARCB1
      expression. Proliferative fasciitis in childhood can have a varied histological
      appearance that can cause confusion with malignancies. Awareness of these
      histological pitfalls is critical to avoid potentially serious diagnostic errors.

PMID- 24863877
TI  - Commentary: Thinking bigger: scaling up innovative practice models.

PMID- 24863878
TI  - Pharmacogenomics in the nursing literature: an integrative review.
AB  - BACKGROUND: Pharmacogenomics is a rapidly growing component of personalized
      health care, and nurses must be competent to deliver genomic-focused nursing
      care. METHODS: We conducted an integrative review of pharmacogenomics in the
      nursing literature. A comprehensive search of the nursing literature was
      conducted using the key words pharmacogenomics and pharmacogenetics. A total of
      47 unique articles were included. RESULTS: Articles represented mainly narrative
      reviews, with limited discussions of the implications for nursing practice,
      education, or research. As such, they provide limited direction for advancing
      either clinical practice or scientific inquiry. CONCLUSIONS: This review serves
      as a call to action for more systematic and empirical publications addressing
      pharmacogenomics in nursing practice, education, and research. Nurses must be
      involved in and contribute to interdisciplinary conversations and burgeoning
      clinical practice initiatives related to pharmacogenomics.

PMID- 24863879
TI  - Regulation of chondrocyte differentiation by IRE1alpha depends on its enzymatic
      activity.
AB  - Bone morphogenetic protein 2(BMP2) is known to activate unfolded protein response
      (UPR) signal molecules in chondrogenesis. Inositol-requiring enzyme-1alpha
      (IRE1alpha),as one of three unfolded protein sensors in UPR signaling pathways,
      can be activated during ER stress. However, the influence on IRE1alpha in
      chondrocyte differentiation has not yet been elucidated. Here we present evidence
      demonstrating that overexpression of IRE1alpha inhibits chondrocyte
      differentiation, as revealed by reduced expression of collagen II (ColII), Sox9,
      collagen X (ColX), matrix metalloproteinase 13 (MMP-13), Indian hedgehog (IHH),
      Runx2 and enhanced expression of parathyroid hormone-related peptide (PTHrP).
      Furthermore, IRE1alpha-mediated inhibition of chondrogenesis depends on its
      enzymatic activity, since its point mutant lacking enzymatic activity completely
      loses this activity. The RNase and Kinase domains of IRE1alpha C-terminal are
      necessary for its full enzymatic activity and inhibition of chondrocyte
      differentiation. Mechanism studies demonstrate that granulin-epithelin
      precursor(GEP), a growth factor known to stimulate chondrogenesis, induced
      IRE1alpha expression in chondrogenesis. The expression of IRE1alpha is depended
      on GEP signaling, and IRE1alpha expression is hardly detectable in GEP(-/-)
      embryos. In addition, IRE1alpha inhibits GEP-mediated chondrocyte differentiation
      as a negative regulator. Altered expression of IRE1alpha in chondrocyte
      hypertrophy was accompanied by altered levels of IHH and PTHrP. Collectively,
      IRE1alpha may be a novel regulator of chondrocyte differentiation by 1)
      inhibition GEP-mediated chondrocyte differentiation as a negative regulator; 2)
      promoting IHH/PTHrP signaling.

PMID- 24863880
TI  - Lysyl oxidase-like 2 (LOXL2) controls tumor-associated cell proliferation through
      the interaction with MARCKSL1.
AB  - Lysyl oxidase-like 2 (LOXL2) is a member of the lysyl oxidase gene family that
      contributes to the invasiveness and metastasis in tumor progression. However, the
      role of LOXL2 in cellular signaling is incompletely understood. In this study, we
      investigated a possible mechanism of LOXL2 function in tumor metastases in vitro,
      using a human breast carcinoma cell line. Myristoylated alanine-rich C kinase
      substrate-like 1 (MARCKSL1), a modulator in the regulation of cellular
      homeostasis, was identified as a LOXL2 interacting protein. We examined the
      binding domains that are required for the interaction between LOXL2 and MARCKSL1.
      The scavenger-receptor domain of LOXL2 was shown to interact with the N-terminal
      domain of MARCKSL1. Luciferase activity was noticeably reduced by the
      transfection of MARCKSL1 in a dose-dependent manner. In addition, over-expression
      of LOXL2 activates cell growth by inhibiting MARCKSL1-induced apoptosis. The
      effect of LOXL2 on cell cycle and apoptosis-related components was also confirmed
      through the silencing of LOXL2 expression. LOXL2 activates the FAK/Akt/mTOR
      signaling pathways, and MARCKSL1 suppresses LOXL2-induced oncogenesis. These
      insights supply evidence that LOXL2 promotes cell proliferation and inhibits
      apoptotic cell death. Taken together, our results indicate an underlying
      mechanism for an increase of LOXL2-related activity in breast tumor cells.

PMID- 24863882
TI  - Nodal signals via beta-arrestins and RalGTPases to regulate trophoblast invasion.
AB  - Placentation is critical for establishing a healthy pregnancy. Trophoblasts
      mediate implantation and placentation and certain subtypes, most notably
      extravillous cytotrophoblast, are highly invasive. Trophoblast invasion is
      tightly regulated by microenvironmental cues that dictate placental morphology
      and depth. In choriocarcinomas, malignant trophoblast cells become hyperinvasive,
      breaching the myometrium and leading to major complications. Nodal, a member of
      the TGF-beta superfamily, is expressed throughout the endometrium during the peri
      implantation period and in invasive trophoblast cells. Nodal promotes the
      invasion of numerous types of cancer cells. However, Nodal's role in trophoblast
      and choriocarcinoma cell invasion is unclear. Here we show that Nodal stimulates
      the invasion of both the non-malignant HTR-8SV/neo trophoblast and JAR
      choriocarcinoma cells in a dose-dependent manner. We found that endogenous beta
      arrestins and Ral GTPases, key regulators of the cell cytoskeleton, are
      constitutively associated with Nodal receptors (ALK4 and ALK7) in trophoblast
      cells and that RalA is colocalized with ALK4 in endocytic vesicles. Nodal
      stimulates endogenous beta-arrestin2 to associate with phospho-ERK1/2, and
      knockdown of beta-arrestin or Ral proteins impairs Nodal-induced trophoblast and
      choriocarcinoma cell invasion. These results demonstrate, for the first time,
      that beta-arrestins and RalGTPases are important regulators of Nodal-induced
      invasion.

PMID- 24863883
TI  - Treatment and survival of patients with occult breast cancer with axillary lymph
      node metastasis: a nationwide retrospective study.
AB  - BACKGROUND AND OBJECTIVES: Occult breast cancer (OBC) accounts for 0.3-1.0% of
      all breast cancers and is a rare presentation of the disease. The present
      retrospective study examined the overall survival and prognostic factors
      associated with OBC in Korea. METHOD: The study included 142 OBC patients
      identified from the Korean Breast Cancer Society cancer registry from January
      1990 to December 2009. All patients had pathologically positive axillary lymph
      nodes (N1-N3) and pathologically and radiologically negative in-breast lesions
      (T0/Tx) based on a retrospective review of the database. RESULTS: No
      statistically significant differences in overall survival were observed between
      patients undergoing axillary lymph node dissection (ALND) only (80.8%), breast
      conserving surgery (BCS) with ALND (98.0%), and mastectomy with ALND (92.5%) with
      P-value of 0.061. Nodal status was a significant prognostic factor (P = 0.004) on
      univariate analysis. When compared with T1 patients group, T0/TxN1 patients
      showed better survival than T1N1 patients (hazard ratio [HR] 0.253; 95%
      confidence interval, 0.104-0.618; P = 0.003), but T0/TxN2, T0/TxN3 patients
      showed similar survival to T1N2, T1N3 patients. CONCLUSIONS: OBC patients treated
      with ALND only showed comparable outcomes to those undergoing ALND combined with
      BCS or mastectomy. Nodal status may be an independent predictor of poor outcome
      in OBC patients.

PMID- 24863881
TI  - Recent progress in the study of the Rheb family GTPases.
AB  - In this review we highlight recent progress in the study of Rheb family GTPases.
      Structural studies using X-ray crystallography and NMR have given us insight into
      unique features of this GTPase. Combined with mutagenesis studies, these works
      have expanded our understanding of residues that affect Rheb GTP/GDP bound
      ratios, effector protein interactions, and stimulation of mTORC1 signaling.
      Analysis of cancer genome databases has revealed that several human carcinomas
      contain activating mutations of the protein. Rheb's role in activating mTORC1
      signaling at the lysosome in response to stimuli has been further elucidated.
      Rheb has also been suggested to play roles in other cellular pathways including
      mitophagy and peroxisomal ROS response. A number of studies in mice have
      demonstrated the importance of Rheb in development, as well as in a variety of
      functions including cardiac protection and myelination. We conclude with a
      discussion of future prospects in the study of Rheb family GTPases.

PMID- 24863884
TI  - Feasibility study of CT perfusion imaging for prostate carcinoma.
AB  - OBJECTIVE: The aim of this feasibility study was to obtain initial data with
      which to assess the efficiency of perfusion CT imaging (CTpI) and to compare this
      with magnetic resonance imaging (MRI) in the diagnosis of prostate carcinoma.
      MATERIALS AND METHODS: This prospective study involved 25 patients with prostate
      carcinoma undergoing MRI and CTpI. All analyses were performed on T2-weighted
      images (T2WI), apparent diffusion coefficient (ADC) maps, diffusion-weighted
      images (DWI) and CTp images. We compared the performance of T2WI combined with
      DWI and CTp alone. The study was approved by the local ethics committee, and
      written informed consent was obtained from all patients. RESULTS: Tumours were
      present in 87 areas according to the histopathological results. The diagnostic
      performance of the T2WI+DWI+CTpI combination was significantly better than that
      of T2WI alone for prostate carcinoma (P < 0.001). The diagnostic value of CTpI
      was similar to that of T2WI+DWI in combination. There were statistically
      significant differences in the blood flow and permeability surface values between
      prostate carcinoma and background prostate on CTp images. CONCLUSION: CTp may be
      a valuable tool for detecting prostate carcinoma and may be preferred in cases
      where MRI is contraindicated. If this technique is combined with T2WI and DWI,
      its diagnostic value is enhanced. KEY POINTS: Perfusion CT is a helpful technique
      for prostate carcinoma diagnosis. *Colour maps allow easy and rapid visual
      assessment of the functional changes. Colour maps of prostate carcinoma provide
      information about in vivo tumoral vascularity. CTp images may be added into
      routine radiological examinations. CTp provides guidance for histopathological
      correlation if biopsy is scheduled.

PMID- 24863885
TI  - Bone marrow oedema on MR imaging indicates ARCO stage 3 disease in patients with
      AVN of the femoral head.
AB  - OBJECTIVES: To test the hypothesis that bone marrow oedema (BME) observed on MRI
      in patients with avascular necrosis (AVN) of the femoral head represents an
      indicator of subchondral fracture. METHODS: Thirty-seven symptomatic hips of 27
      consecutive patients (53% women, mean age 49.2) with AVN of the femoral head and
      associated BME on magnetic resonance (MR) imaging were included. MR findings were
      correlated with computed tomography (CT) of the hip and confirmed by
      histopathological examination of the resected femoral head. Imaging studies were
      analysed by two radiologists with use of the ARCO classification. RESULTS: On MR
      imaging a fracture line could be identified in 19/37 (51%) cases, which were
      classified as ARCO stage 3 (n = 15) and stage 4 (n = 4). The remaining 18/37
      (49%) cases were classified as ARCO stage 2. However, in all 37/37 (100%) cases a
      subchondral fracture was identified on CT, indicating ARCO stage 3/4 disease. The
      extent of subchondral fractures and the femoral head collapse was graded higher
      on CT as compared to MRI (P < 0.05). Histopathological analysis confirmed bone
      necrosis and subchondral fractures. CONCLUSIONS: In patients with AVN, BME of the
      femoral head represents a secondary sign of subchondral fracture and thus
      indicates ARCO stage 3 disease. KEY POINTS: BME on MRI in AVN of femoral head
      indicates a subchondral fracture. BME in AVN of the femoral head represents ARCO
      stage 3/4 disease. CT identifies subchondral fractures and femoral head collapse
      better than MR imaging. This knowledge helps to avoid understaging and to trigger
      adequate treatment.

PMID- 24863886
TI  - Pulmonary MRA: differentiation of pulmonary embolism from truncation artefact.
AB  - PURPOSE: Truncation artefact (Gibbs ringing) causes central signal drop within
      vessels in pulmonary magnetic resonance angiography (MRA) that can be mistaken
      for emboli, reducing diagnostic accuracy for pulmonary embolism (PE). We propose
      a quantitative approach to differentiate truncation artefact from PE. METHODS:
      Twenty-eight patients who underwent pulmonary computed tomography angiography
      (CTA) for suspected PE were recruited for pulmonary MRA. Signal intensity drops
      within pulmonary arteries that persisted on both arterial-phase and delayed-phase
      MRA were identified. The percent signal loss between the vessel lumen and central
      drop was measured. CTA served as the reference standard for presence of pulmonary
      emboli. RESULTS: A total of 65 signal intensity drops were identified on MRA. Of
      these, 48 (74%) were artefacts and 17 (26%) were PE, as confirmed by CTA.
      Truncation artefacts had a significantly lower median signal drop than PE on both
      arterial-phase (26% [range 12-58%] vs. 85% [range 53-91%]) and delayed-phase MRA
      (26% [range 11-55%] vs. 77% [range 47-89%]), p < 0.0001 for both. Receiver
      operating characteristic (ROC) analyses revealed a threshold value of 51%
      (arterial phase) and 47% signal drop (delayed phase) to differentiate between
      truncation artefact and PE with 100% sensitivity and greater than 90%
      specificity. CONCLUSION: Quantitative signal drop is an objective tool to help
      differentiate truncation artefact and pulmonary embolism in pulmonary MRA. KEY
      POINTS: * Inexperienced readers may mistake truncation artefacts for emboli on
      pulmonary MRA * Pulmonary emboli have non-uniform signal drop * 51% (arterial
      phase) and 47% (delayed phase) cut-off differentiates truncation artefact from PE
      * Quantitative signal drop measurement enables more accurate pulmonary embolism
      diagnosis with MRA.

PMID- 24863888
TI  - Brief report. Embryonic arterial and skeletal dysgenesis: Syracuse colloquium on
      congenital arterial and skeletal birth defects September 28 and 29, 2013.

PMID- 24863887
TI  - Assessment of acute intestinal graft versus host disease by abdominal magnetic
      resonance imaging at 3 Tesla.
AB  - OBJECTIVES: After allogeneic stem cell transplantation (SCT), a reliable
      diagnosis of acute graft versus host disease (aGvHD) is essential for an early
      and successful treatment. It is the aim of this analysis to assess intestinal
      aGvHD by magnetic resonance imaging (MRI). METHODS: Prior to allogeneic SCT, 64
      consecutive patients underwent abdominal MRI examination on a 3 T MR system,
      including axial and coronal T2w sequences and a three-dimensional dynamic T1w,
      contrast enhanced sequence. After SCT, 20 patients with suspected aGvHD received
      a second MRI as well as an endoscopic examination. RESULTS: Nine patients
      suffered from histologically proven intestinal aGvHD. In eleven patients
      intestinal aGvHD was excluded. In all aGvHD patients typical MRI findings with
      long-segment bowel wall thickening--always involving the terminal ileum--with
      profound submucosal oedema, were detected. The bowel wall was significantly
      thickened in patients with intestinal aGvHD. Bowel contrast enhancement spared
      the submucosa while demonstrating strong mucosal hyperemia. CONCLUSIONS: In
      intestinal aGvHD, a characteristic MR-appearance can be detected. This MRI
      pattern might facilitate an early and non-invasive diagnosis of intestinal aGvHD.
      MRI might thus be used as a sensitive tool to rule out or support the clinical
      diagnosis of aGvHD. KEY POINTS: * Acute intestinal graft versus host disease
      (aGvHD) can be assessed by MRI. * The aGvHD of the bowel demonstrates a
      characteristic MR imaging pattern. * Bowel wall shows extensive long-segment wall
      thickening with profound submucosal oedema. * Terminal ileum seems invariably
      affected; other bowel segments show variable involvement. * Colonoscopy in
      suspected aGvHD should include inspection of terminal ileum.

PMID- 24863889
TI  - Nuchal translucency thickness in the prediction of unbalanced translocations.
AB  - OBJECTIVE: The aim of this study was to assess the role of nuchal translucency
      (NT) in the prediction of unbalanced translocation in offspring of couples in
      which one of the parents is a balanced translocation carrier. MATERIAL AND
      METHODS: From January 1996 to December 2012, fetal NT was measured before
      chorionic villus sampling in 86 pregnancies referred because of parental balanced
      translocation. RESULTS: No significant differences in pregnancy characteristics
      and in NT expressed in millimetres or in multiples of the median (MoMs) were
      observed between the 41 fetuses with a normal karyotype [1.72 mm, 95% confidence
      interval (CI): 1.49-1.96; 1.14 MoM; 95% CI: 1.01-1.26], the 38 fetuses with
      balanced translocations (1.78 mm, 95% CI: 1.44-2.12; 1.22 MoM; 95% CI: 1.01-1.43)
      and the 7 fetuses with unbalanced translocations (2.21 mm, 95% CI: 1.33-3.09;
      1.59 MoM; 95% CI: 0.72-2.45). The proportions of fetuses with NT above 95th
      centile in the three groups were 9.1% in fetuses with normal karyotype, 18.4% in
      balanced translocations and 28.6% in unbalanced translocations, not significantly
      different. CONCLUSION: Although a trend to an increased NT was observed in
      fetuses with unbalanced translocation, no significant differences were reached.
      According to our results, a normal NT evaluation should not preclude the
      performance of CVS in pregnancies of balanced translocation parents.

PMID- 24863890
TI  - In situ vadose zone bioremediation.
AB  - Contamination of the vadose zone with various pollutants is a world-wide problem,
      and often technical or economic constraints impose remediation without
      excavation. In situ bioremediation in the vadose zone by bioventing has become a
      standard remediation technology for light spilled petroleum products. In this
      review, focus is given on new in situ bioremediation strategies in the vadose
      zone targeting a variety of other pollutants such as perchlorate, nitrate,
      uranium, chromium, halogenated solvents, explosives and pesticides. The
      techniques for biostimulation of either oxidative or reductive degradation
      pathways are presented, and biotransformations to immobile pollutants are
      discussed in cases of non-degradable pollutants. Furthermore, research on natural
      attenuation in the vadose zone is presented. 

PMID- 24863891
TI  - Emerging chemicals and the evolution of biodegradation capacities and pathways in
      bacteria.
AB  - The number of new chemicals produced is increasing daily by the thousands, and it
      is inevitable that many of these chemicals will reach the environment. Current
      research provides an understanding of how the evolution of promiscuous enzymes
      and the recruitment of enzymes available from the metagenome allows for the
      assembly of these pathways. Nevertheless, physicochemical constraints including
      bioavailability, bioaccessibility, and the structural variations of similar
      chemicals limit the evolution of biodegradation pathways. Similarly,
      physiological constraints related to kinetics and substrate utilization at low
      concentrations likewise limit chemical-enzyme interactions and consequently
      evolution. Considering these new data, the biodegradation decalogue still proves
      valid while at the same time the underlying mechanisms are better understood. 

PMID- 24863892
TI  - Agricultural soils, pesticides and microbial diversity.
AB  - Pesticide effects on microbial community structure and activity in soil are
      reviewed, showing that methodological developments within the past few years have
      generated new possibilities for assessing pesticide effects. The first example is
      the use of mRNA quantification showing that nitrification processes are indeed
      very susceptible to some pesticides, and that there is correlation between the
      mRNA transcript quantity and the nitrification rate. The second example is
      devoted to pesticides influencing microbial community structures. The emergence
      of high throughput sequencing techniques now allows a more detailed analysis of
      which bacterial species are influenced. 

PMID- 24863893
TI  - Syntrophic biodegradation of hydrocarbon contaminants.
AB  - Anaerobic environments are crucial to global carbon cycling wherein the microbial
      metabolism of organic matter occurs under a variety of redox conditions. In many
      anaerobic ecosystems, syntrophy plays a key role wherein microbial species must
      cooperate, essentially as a single catalytic unit, to metabolize substrates in a
      mutually beneficial manner. Hydrocarbon-contaminated environments such as
      groundwater aquifers are typically anaerobic, and often methanogenic. Syntrophic
      processes are needed to biodegrade hydrocarbons to methane, and recent studies
      suggest that syntrophic hydrocarbon metabolism can also occur in the presence of
      electron acceptors. The elucidation of key features of syntrophic processes in
      defined co-cultures has benefited greatly from advances in 'omics' based tools.
      Such tools, along with approaches like stable isotope probing, are now being used
      to monitor carbon flow within an increasing number of hydrocarbon-degrading
      consortia to pinpoint the key microbial players involved in the degradative
      pathways. The metagenomic sequencing of hydrocarbon-utilizing consortia should
      help to further identify key syntrophic features and define microbial
      interactions in these complex communities. 

PMID- 24863895
TI  - Lignin plays a negative role in the biochemical process for producing
      lignocellulosic biofuels.
AB  - A biochemical platform holds the most promising route toward lignocellulosic
      biofuels, in which polysaccharides are hydrolyzed by cellulase enzymes into
      simple sugars and fermented to ethanol by microbes. However, these
      polysaccharides are cross-linked in the plant cell walls with the hydrophobic
      network of lignin that physically impedes enzymatic deconstruction. A
      thermochemical pretreatment process is often required to remove or delocalize
      lignin, which may also generate inhibitors that hamper enzymatic hydrolysis and
      fermentation. Here we review recent advances in understanding lignin structure in
      the plant cell walls and the negative roles of lignin in the processes of
      converting biomass to biofuels. Perspectives and future directions to improve the
      biomass conversion process are also discussed. 

PMID- 24863894
TI  - Metabolic potential of endophytic bacteria.
AB  - The bacterial endophytic microbiome promotes plant growth and health and
      beneficial effects are in many cases mediated and characterized by metabolic
      interactions. Recent advances have been made in regard to metabolite production
      by plant microsymbionts showing that they may produce a range of different types
      of metabolites. These substances play a role in defense and competition, but may
      also be needed for specific interaction and communication with the plant host.
      Furthermore, few examples of bilateral metabolite production are known and
      endophytes may modulate plant metabolite synthesis as well. We have just started
      to understand such metabolic interactions between plants and endophytes, however,
      further research is needed to more efficiently make use of beneficial plant
      microbe interactions and to reduce pathogen infestation as well as to reveal
      novel bioactive substances of commercial interest. 

PMID- 24863896
TI  - Hydrocarbon biodegradation in intertidal wetland sediments.
AB  - Intertidal wetlands, primarily salt marsh, mangrove and mudflats, which provide
      many essential ecosystem services, are under threat on numerous fronts; a
      situation that is made worse by crude-oil pollution. Microbes are the main
      vehicle for remediation of such sediments, and new discoveries, such as novel
      biodegradation pathways, means of accessing oil, multi-species interactions, and
      community-level responses to oil addition, are helping us to understand, predict
      and monitor the fate of oil. Despite this, there are many challenges, not least
      because of the heterogeneity of these ecosystems and the complexity of crude oil.
      For example, there is growing awareness about the toxicity of the oxygenated
      products that result from crude-oil weathering, which are difficult to degrade.
      This review highlights how developments in areas as diverse as systems biology,
      microbiology, ecology, biogeochemistry and analytical chemistry are enhancing our
      understanding of hydrocarbon biodegradation and thus bioremediation of oil
      polluted intertidal wetlands. 

PMID- 24863897
TI  - Linking microbial community structure, interactions and function in anaerobic
      digesters using new molecular techniques.
AB  - Over the last decade there has been a rapid development in culture-independent
      techniques for exploring microbial communities, which have led to new insights
      into their structure and function in both natural environments and engineered
      systems. This review focuses on some of the most important recent advances and
      their applications to the diverse microbial communities associated with anaerobic
      digestion. The use of these approaches in combination with complementary imaging
      techniques, chemical isotope analyses and detailed reactor performance
      measurements provides a new opportunity to develop a fundamental understanding of
      how microbial community dynamics, interactions and functionality influence
      digester efficiency and stability. 

PMID- 24863898
TI  - Microbiomes in bioenergy production: from analysis to management.
AB  - Currently, bioreactors exploiting natural microbial communities, that is,
      microbiomes, for bioenergy production are almost exclusively operated based on
      bulk parameters and empirical expert knowledge. The microbiome of these
      bioreactors often remains a "black box", that is, its composition and function
      are only analyzed retrospectively (mostly in a case of failure). Here, on-time
      microbiome analysis can allow a proactive process management. However, today's
      sophisticated molecular ecology methods appear inaccessible for the routine
      analysis of reactor microbiomes in bioenergy production. This review analyzes the
      requirements of methods for routine microbiome diagnostics. Especially the
      ability of current molecular and cell based methods to derive structure-function
      relationships, that is, correlations between the microbial community structure
      and dynamics and the reactor performance, are emphasized and key-criteria for
      routine on-site monitoring are defined. Finally, a critical assessment of
      selected methods for microbiome monitoring is performed focusing on (i) the
      production of biogas in anaerobic digesters and (ii) the production of the
      biofuel precursor n-butyrate. 

PMID- 24863899
TI  - Five reasons to use bacteria when assessing manufactured nanomaterial
      environmental hazards and fates.
AB  - Manufactured nanomaterials (MNMs) are increasingly incorporated into everyday
      products and thus are entering the environment via manufacturing, product use,
      and waste disposal. Still, understanding MNM environmental hazards and fates lags
      MNM industry growth. To catch up, keep pace, and influence future MNM safe design
      strategies, rapid safety assessments are needed. Bacteria are important
      ecological nanotoxicology targets to consider when assessing MNM safety: bacteria
      are exposed to MNMs in water, sewage, soils, and sediments, wherein they
      influence MNM fates; bacteria can also be impacted-with potential health and
      ecosystem consequences. Routinely using bacteria for assessing MNMs would promote
      effective management of the environmental risks of this rapidly growing industry,
      but appropriate protocols and policies for this assessment need to be instituted.

PMID- 24863900
TI  - Trash to treasure: production of biofuels and commodity chemicals via syngas
      fermenting microorganisms.
AB  - Fermentation of syngas is a means through which unutilized organic waste streams
      can be converted biologically into biofuels and commodity chemicals. Despite
      recent advances, several issues remain which limit implementation of industrial
      scale syngas fermentation processes. At the cellular level, the energy
      conservation mechanism of syngas fermenting microorganisms has not yet been
      entirely elucidated. Furthermore, there was a lack of genetic tools to study and
      ultimately enhance their metabolic capabilities. Recently, substantial progress
      has been made in understanding the intricate energy conservation mechanisms of
      these microorganisms. Given the complex relationship between energy conservation
      and metabolism, strain design greatly benefits from systems-level approaches.
      Numerous genetic manipulation tools have also been developed, paving the way for
      the use of metabolic engineering and systems biology approaches. Rational strain
      designs can now be deployed resulting in desirable phenotypic traits for large
      scale production. 

PMID- 24863901
TI  - Microbial nanowires for bioenergy applications.
AB  - Microbial nanowires are electrically conductive filaments that facilitate long
      range extracellular electron transfer. The model for electron transport along
      Shewanella oneidensis nanowires is electron hopping/tunneling between cytochromes
      adorning the filaments. Geobacter sulfurreducens nanowires are comprised of pili
      that have metal-like conductivity attributed to overlapping pi-pi orbitals of
      aromatic amino acids. The nanowires of Geobacter species have been implicated in
      direct interspecies electron transfer (DIET), which may be an important mode of
      syntrophy in the conversion of organic wastes to methane. Nanowire networks
      confer conductivity to Geobacter biofilms converting organic compounds to
      electricity in microbial fuel cells (MFCs) and increasing nanowire production is
      the only genetic manipulation shown to yield strains with improved current
      producing capabilities. Introducing nanowires, or nanowire mimetics, might
      improve other bioenergy strategies that rely on extracellular electron exchange,
      such as microbial electrosynthesis. Similarities between microbial nanowires and
      synthetic conducting polymers suggest additional energy-related applications. 

PMID- 24863902
TI  - Towards a molecular-level theory of carbohydrate processivity in glycoside
      hydrolases.
AB  - Polysaccharide depolymerization in nature is primarily accomplished by processive
      glycoside hydrolases (GHs), which abstract single carbohydrate chains from
      polymer crystals and cleave glycosidic linkages without dissociating after each
      catalytic event. Understanding the molecular-level features and structural
      aspects of processivity is of importance due to the prevalence of processive GHs
      in biomass-degrading enzyme cocktails. Here, we describe recent advances towards
      the development of a molecular-level theory of processivity for cellulolytic and
      chitinolytic enzymes, including the development of novel methods for measuring
      rates of key steps in processive action and insights gained from structural and
      computational studies. Overall, we present a framework for developing structure
      function relationships in processive GHs and outline additional progress towards
      developing a fundamental understanding of these industrially important enzymes. 

PMID- 24863903
TI  - Latent tuberculosis infection in patients with chronic plaque psoriasis who are
      candidates for biological therapy.
AB  - BACKGROUND: Screening for latent tuberculosis infection (LTBI) is mandatory in
      patients with psoriasis prior to biological therapy. OBJECTIVES: To investigate
      the prevalence of LTBI in patients with psoriasis who are candidates for
      biological therapy. METHODS: LTBI was investigated in patients with moderate-to
      severe psoriasis (n = 243), Crohn disease (n = 64) or rheumatoid arthritis (RA)
      (n = 56) and in healthcare workers (n = 1683). LTBI diagnosis was based on
      positive QuantiFERON-B Gold In-Tube (QFT-GIT) in vitro assay without any
      clinical, radiological or microbiological evidence of active tuberculosis.
      RESULTS: LTBI was diagnosed in 8.2% of patients with psoriasis, 7% with Crohn
      disease and 9% with RA, and in 8.8% of healthcare workers (P = 0.9). Patients
      with psoriasis who also had LTBI (n = 20) received a 9-month prophylaxis with
      isoniazid (5 mg kg(-1) daily). None of these patients developed active
      tuberculosis infection after receiving biological therapy (etanercept,
      adalimumab, infliximab or ustekinumab) for 37 +/- 32 weeks (mean +/- SD). All
      patients with psoriasis were retested for LTBI after 31 +/- 1.7 months. Five of
      the 20 patients with LTBI presented QFT-GIT reversion and two patients out of 243
      (0.8%) had QFT-GIT conversion and received antibiotic prophylaxis. CONCLUSIONS:
      The prevalence of LTBI in patients with psoriasis is similar to that in patients
      with Crohn disease or RA and in healthcare workers. Prophylaxis with isoniazid is
      effective in preventing tuberculosis reactivation in patients with LTBI receiving
      biological therapy.

PMID- 24863905
TI  - Primary Sjogren's syndrome in monozygotic twins.

PMID- 24863904
TI  - Divergence with gene flow in a population of thermophilic bacteria: a potential
      role for spatially varying selection.
AB  - A fundamental goal of evolutionary biology is to understand how ecological
      diversity arises and is maintained in natural populations. We have investigated
      the contributions of gene flow and divergent selection to the distribution of
      genetic variation in an ecologically differentiated population of a thermophilic
      cyanobacterium (Mastigocladus laminosus) found along the temperature gradient of
      a nitrogen-limited stream in Yellowstone National Park. For most loci sampled,
      gene flow appears to be sufficient to prevent substantial genetic divergence.
      However, one locus (rfbC) exhibited a comparatively low migration rate as well as
      other signatures expected for a gene experiencing spatially varying selection,
      including an excess of common variants, an elevated level of polymorphism and
      extreme genetic differentiation along the gradient. rfbC is part of an expression
      island involved in the production of the polysaccharide component of the
      protective envelope of the heterocyst, the specialized nitrogen-fixing cell of
      these bacteria. SNP genotyping in the vicinity of rfbC revealed a ~5-kbp region
      including a gene content polymorphism that is tightly associated with
      environmental temperature and therefore likely contains the target of selection.
      Two genes have been deleted both in the predominant haplotype found in the
      downstream region of White Creek and in strains from other Yellowstone
      populations of M. laminosus, which may result in the production of heterocysts
      with different envelope properties. This study implicates spatially varying
      selection in the maintenance of variation related to thermal performance at White
      Creek despite on-going or recent gene flow. 

PMID- 24863906
TI  - Kinematics of preferred and non-preferred handballing in Australian football.
AB  - In Australian football (AF), handballing proficiently with both the preferred and
      non-preferred arm is important at elite levels; yet, little information is
      available for handballing on the non-preferred arm. This study compared preferred
      and non-preferred arm handballing techniques. Optotrak Certus (100 Hz) collected
      three-dimensional data for 19 elite AF players performing handballs with the
      preferred and non-preferred arms. Position data, range of motion (ROM), and
      linear and angular velocities were collected and compared between preferred and
      non-preferred arms using dependent t-tests. The preferred arm exhibited
      significantly greater forearm and humerus ROM and angular velocity and
      significantly greater shoulder angular velocity at ball contact compared to the
      non-preferred arm. In addition, the preferred arm produced a significantly
      greater range of lateral bend and maximum lower-trunk speed, maximum strike-side
      hip speed and hand speed at ball contact than the non-preferred arm. The non
      preferred arm exhibited a significantly greater shoulder angle and lower- and
      upper-trunk orientation angle, but significantly lower support-elbow angle, trunk
      ROM, and trunk rotation velocity compared to the preferred arm. Reduced ROM and
      angular velocities found in non-preferred arm handballs indicates a reduction in
      the degrees of freedom and a less developed skill. Findings have implication for
      development of handballing on the non-preferred arm.

PMID- 24863908
TI  - [Adipose-derived stromal cells (ASC) - basics and therapeutic approaches in
      otorhinolaryngology].
AB  - Adipose-derived Stromal Cells (ASC) - Basics and Therapeutic Approaches in
      Otorhinolaryngology Mesenchymal stem cells from adipose tissue can be easily
      harvested with less discomfort, low donor-site morbidity and high amount compared
      to bone marrow-derived stem cells. Due to their multilineage differentiation
      potential in various cell types, immunmodulatory properties and their capability
      to enhance wound healing, ASC are a promising cell source for tissue engineering
      approaches and regenerative medicine. They are characterized by the expression of
      specific surface marker proteins and their differentiation potential into the
      mesenchymal lineages. Whereas only preclinical studies are published for
      otorhinolaryngology-related therapeutic options using ASC, various diseases, for
      instance graft-versus-host disease, have already been treated with ASC in single
      cases or clinical trials. Safety and genomic stability of ASC as well as the risk
      of spontaneous malignant transformation are still disputed. This review
      summarizes the current literature on characterization and anatomic localization
      of ASC. In addition, beside the presentation of preclinical studies concerning
      therapeutic approaches in otorhinolaryngology as well as of current clinical
      applications, the issue of safety of ASC in human stem cell therapy is discussed.

PMID- 24863910
TI  - [A new implant system for orbital prosthetic rehabilitation: "epiplating mono"].
AB  - A New Implant System for Orbital Prosthetic Rehabilitation: "Epiplating Mono"
      Prosthetic or episthetic rehabilitation of ear, eye and nose are currently most
      common performed using magnetic fixation. While at the beginning single implants
      have been used, now-a-days a more extended approach with plate fixation are
      recommended to enhance the stability of the anchored magnets. A newly designed
      implant system epiplating mono is presented that combines the structure of a
      single implant with additional fixation elements. In a pilot study this new
      implant system was used in 4 patients for prosthetic orbital rehabilitation.
      Further experiences with this new implant system are required necessitating long
      term experiences of implant stability to define the value of the presented
      epiplating mono system for prosthetic rehabilitation. 

PMID- 24863911
TI  - [Unexpected severe degradation of speech recognition in a patient with cochlear
      implant].

PMID- 24863912
TI  - [Acute dyspnea in COPD and asthma bronchiale].

PMID- 24863913
TI  - [Obligation to inform about spinal cord damage such as tetraplegia as possible
      damage from patient positioning during long duration forward flexion of the
      cervical spine in general anesthesia for tracheoplasty].

PMID- 24863914
TI  - [Differential diagnosis of headaches].
AB  - Headache is a frequent symptom in otorhinolaryngology. Such a secondary headache
      is typically caused by an organic disease in the head and neck area. Much more
      frequent is primary headache i.e. that an organic cause cannot be found. The most
      frequent primary headache types are migraine, tension-type headache, and cluster
      headache. What has to be done when the otorhinolaryngologist cannot find a cause
      for a headache in the head and neck area? This continuing education article
      should enable the otorhinolaryngologist to perform a first differential
      diagnostic exploration. Often a detailed inquiry of the patient's history and a
      clinical examination are sufficient to decide to which other medical discipline
      the patient should be referred. Furthermore, the article should enable the reader
      to capture red flag symptoms, i.e. to catch symptoms accompanying the headache
      that might be related to underlying and life-threatening disease. 

PMID- 24863915
TI  - [Sphenoethmoidectomy with or without sinusotomy type I, II, III - I].

PMID- 24863916
TI  - Alginate/chitosan nanoparticles for encapsulation and controlled release of
      vitamin B2.
AB  - This work aims at evaluating encapsulation and controlled release of vitamin B2
      from alginate/chitosan nanoparticles. Ionotropic polyelectrolyte pre-gelation was
      used as production method being chitosan and alginate used as main materials.
      Nanoparticles were characterized in terms of average size, polydispersity index
      (PDI), zeta potential and vitamin entrapment efficiency. The average size for
      alginate/chitosan nanoparticles was 119.5+/-49.9nm for samples without vitamin B2
      and 104.0+/-67.2nm with the encapsulation of vitamin B2, presenting a PDI of
      0.454+/-0.066 and 0.319+/-0.068, respectively. The nanoparticles showed
      encapsulation efficiency and loading capacity values of 55.9+/-5.6% and 2.2+/
      0.6%, respectively. Release profiles were evaluated at different conditions
      showing that the polymeric relaxation was the most influent phenomenon in vitamin
      B2 release. In order to study their stability nanoparticles were stored at 4
      degrees C being particles sizes and PDI evaluated during 5 months showing the
      results that vitamin B2-loaded nanoparticles are more stable (in terms of size
      and PDI) than nanoparticles without vitamin B2. 

PMID- 24863917
TI  - Fabrication, characterization and bioevaluation of silibinin loaded chitosan
      nanoparticles.
AB  - Silibinin is reported to possess multiple biological activities. However, its
      hydrophobic nature limits its bioavailability compromising in vivo biological
      activities. Nanoparticles-based delivery of such molecules has emerged as new
      technique to resolve these issues. Bio-degradable, compatible and adhesive nature
      of chitosan has recently attracted its suitability as a carrier for biologically
      active molecules. This study presents fabrication and characterization of
      chitosan-tripolyphosphate based encapsulation of silibinin. Various preparations
      of silibinin encapsulated chitosan-tripolyphosphate nanoparticles were studied
      for particle size, morphology, zeta-potential, and encapsulation efficiencies.
      Preparations were also evaluated for cytotoxic activities in vitro. The optimized
      silibinin loaded chitosan nanoparticles were of 263.7+/-4.1nm in particle size
      with zeta potential 37.4+/-1.57mV. Nanoparticles showed high silibinin
      encapsulation efficiencies (82.94+/-1.82%). No chemical interactions between
      silibinin and chitosan were observed in FTIR analysis. Powder X-ray diffraction
      analysis revealed transformed physical state of silibinin after encapsulation.
      Surface morphology and thermal behaviour were determined using TEM and DSC
      analysis. Encapsulated silibinin displayed increased dissolution and better
      cytotoxicity against human prostate cancer cells (DU145) than silibinin alone. 

PMID- 24863918
TI  - Nanoparticle as signaling protein mimic: robust structural and functional
      modulation of CaMKII upon specific binding to fullerene C60 nanocrystals.
AB  - In a biological environment, nanoparticles encounter and interact with thousands
      of proteins, forming a protein corona on the surface of the nanoparticles, but
      these interactions are oftentimes perceived as nonspecific protein adsorption,
      with protein unfolding and deactivation as the most likely consequences. The
      potential of a nanoparticle-protein interaction to mimic a protein-protein
      interaction in a cellular signaling process, characterized by stringent binding
      specificity and robust functional modulation for the interacting protein, has not
      been adequately demonstrated. Here, we show that water-suspended fullerene C60
      nanocrystals (nano-C60) interact with and modulate the function of the
      Ca(2+)/calmodulin-dependent protein kinase II (CaMKII), a multimeric
      intracellular serine/threonine kinase central to Ca(2+) signal transduction, in a
      fashion that rivals the well-documented interaction between the NMDA (N-methyl-d
      aspartate) receptor subunit NR2B protein and CaMKII. The stable high-affinity
      binding of CaMKII to distinct sites on nano-C60, mediated by amino acid residues
      D246 and K250 within the catalytic domain of CaMKIIalpha, but not the nonspecific
      adsorption of CaMKII to diamond nanoparticles, leads to functional consequences
      reminiscent of the NR2B-CaMKII interaction, including generation of autonomous
      CaMKII activity after Ca(2+) withdrawal, calmodulin trapping and CaMKII
      translocation to postsynaptic sites. Our results underscore the critical
      importance of specific interactions between nanoparticles and cellular signaling
      proteins, and the ability of nano-C60 to sustain the autonomous kinase activity
      of CaMKII may have significant implications for both the biosafety and the
      potential therapeutic applications of fullerene C60. 

PMID- 24863919
TI  - Health care workers, mandatory influenza vaccination policies and the law.

PMID- 24863921
TI  - More inequality with demise of health accord.

PMID- 24863920
TI  - Measles vaccination: a shot of common sense.

PMID- 24863922
TI  - Feds and industry to overhaul clinical trials.

PMID- 24863924
TI  - Canada not immune to spread of polio.

PMID- 24863925
TI  - 10 health stories that mattered: May 19-23.

PMID- 24863926
TI  - Oil and medicine: Alberta MDs gain support.

PMID- 24863923
TI  - Effect of prone positioning during mechanical ventilation on mortality among
      patients with acute respiratory distress syndrome: a systematic review and meta
      analysis.
AB  - BACKGROUND: Mechanical ventilation in the prone position is used to improve
      oxygenation and to mitigate the harmful effects of mechanical ventilation in
      patients with acute respiratory distress syndrome (ARDS). We sought to determine
      the effect of prone positioning on mortality among patients with ARDS receiving
      protective lung ventilation. METHODS: We searched electronic databases and
      conference proceedings to identify relevant randomized controlled trials (RCTs)
      published through August 2013. We included RCTs that compared prone and supine
      positioning during mechanical ventilation in patients with ARDS. We assessed risk
      of bias and obtained data on all-cause mortality (determined at hospital
      discharge or, if unavailable, after longest follow-up period). We used random
      effects models for the pooled analyses. RESULTS: We identified 11 RCTs (n=2341)
      that met our inclusion criteria. In the 6 trials (n=1016) that used a protective
      ventilation strategy with reduced tidal volumes, prone positioning significantly
      reduced mortality (risk ratio 0.74, 95% confidence interval 0.59-0.95; I2=29%)
      compared with supine positioning. The mortality benefit remained in several
      sensitivity analyses. The overall quality of evidence was high. The risk of bias
      was low in all of the trials except one, which was small. Statistical
      heterogeneity was low (I2<50%) for most of the clinical and physiologic outcomes.
      INTERPRETATION: Our analysis of high-quality evidence showed that use of the
      prone position during mechanical ventilation improved survival among patients
      with ARDS who received protective lung ventilation.

PMID- 24863927
TI  - Two-stage hepatectomy for liver metastasis from colorectal cancer.

PMID- 24863928
TI  - Of Juno, neuropeptide release, and light-activated chloride channels.

PMID- 24863929
TI  - Calmodulin regulation (calmodulation) of voltage-gated calcium channels.
AB  - Calmodulin regulation (calmodulation) of the family of voltage-gated CaV1-2
      channels comprises a prominent prototype for ion channel regulation, remarkable
      for its powerful Ca(2+) sensing capabilities, deep in elegant mechanistic
      lessons, and rich in biological and therapeutic implications. This field thereby
      resides squarely at the epicenter of Ca(2+) signaling biology, ion channel
      biophysics, and therapeutic advance. This review summarizes the historical
      development of ideas in this field, the scope and richly patterned organization
      of Ca(2+) feedback behaviors encompassed by this system, and the long-standing
      challenges and recent developments in discerning a molecular basis for
      calmodulation. We conclude by highlighting the considerable synergy between
      mechanism, biological insight, and promising therapeutics. 

PMID- 24863930
TI  - Functional ryanodine receptors in the membranes of neurohypophysial secretory
      granules.
AB  - Highly localized Ca(2+) release events have been characterized in several
      neuronal preparations. In mouse neurohypophysial terminals (NHTs), such events,
      called Ca(2+) syntillas, appear to emanate from a ryanodine-sensitive
      intracellular Ca(2+) pool. Traditional sources of intracellular Ca(2+) appear to
      be lacking in NHTs. Thus, we have tested the hypothesis that large dense core
      vesicles (LDCVs), which contain a substantial amount of calcium, represent the
      source of these syntillas. Here, using fluorescence immunolabeling and immunogold
      labeled electron micrographs of NHTs, we show that type 2 ryanodine receptors
      (RyRs) are localized specifically to LDCVs. Furthermore, a large conductance
      nonspecific cation channel, which was identified previously in the vesicle
      membrane and has biophysical properties similar to that of an RyR, is
      pharmacologically affected in a manner characteristic of an RyR: it is activated
      in the presence of the RyR agonist ryanodine (at low concentrations) and blocked
      by the RyR antagonist ruthenium red. Additionally, neuropeptide release
      experiments show that these same RyR agonists and antagonists modulate Ca(2+)
      elicited neuropeptide release from permeabilized NHTs. Furthermore, amperometric
      recording of spontaneous release events from artificial transmitter-loaded
      terminals corroborated these ryanodine effects. Collectively, our findings
      suggest that RyR-dependent syntillas could represent mobilization of Ca(2+) from
      vesicular stores. Such localized vesicular Ca(2+) release events at the precise
      location of exocytosis could provide a Ca(2+) amplification mechanism capable of
      modulating neuropeptide release physiologically. 

PMID- 24863931
TI  - Interactions between permeation and gating in the TMEM16B/anoctamin2 calcium
      activated chloride channel.
AB  - At least two members of the TMEM16/anoctamin family, TMEM16A (also known as
      anoctamin1) and TMEM16B (also known as anoctamin2), encode Ca(2+)-activated Cl(-)
      channels (CaCCs), which are found in various cell types and mediate numerous
      physiological functions. Here, we used whole-cell and excised inside-out patch
      clamp to investigate the relationship between anion permeation and gating, two
      processes typically viewed as independent, in TMEM16B expressed in HEK 293T
      cells. The permeability ratio sequence determined by substituting Cl(-) with
      other anions (PX/PCl) was SCN(-) > I(-) > NO3 (-) > Br(-) > Cl(-) > F(-) >
      gluconate. When external Cl(-) was substituted with other anions, TMEM16B
      activation and deactivation kinetics at 0.5 uM Ca(2+) were modified according to
      the sequence of permeability ratios, with anions more permeant than Cl(-) slowing
      both activation and deactivation and anions less permeant than Cl(-) accelerating
      them. Moreover, replacement of external Cl(-) with gluconate, or sucrose, shifted
      the voltage dependence of steady-state activation (G-V relation) to more positive
      potentials, whereas substitution of extracellular or intracellular Cl(-) with
      SCN(-) shifted G-V to more negative potentials. Dose-response relationships for
      Ca(2+) in the presence of different extracellular anions indicated that the
      apparent affinity for Ca(2+) at +100 mV increased with increasing permeability
      ratio. The apparent affinity for Ca(2+) in the presence of intracellular SCN(-)
      also increased compared with that in Cl(-). Our results provide the first
      evidence that TMEM16B gating is modulated by permeant anions and provide the
      basis for future studies aimed at identifying the molecular determinants of
      TMEM16B ion selectivity and gating. 

PMID- 24863932
TI  - Signal transmission within the P2X2 trimeric receptor.
AB  - P2X2 receptor channel, a homotrimer activated by the binding of extracellular
      adenosine triphosphate (ATP) to three intersubunit ATP-binding sites (each
      located ~50 A from the ion permeation pore), also shows voltage-dependent
      activation upon hyperpolarization. Here, we used tandem trimeric constructs
      (TTCs) harboring critical mutations at the ATP-binding, linker, and pore regions
      to investigate how the ATP activation signal is transmitted within the trimer and
      how signals generated by ATP and hyperpolarization converge. Analysis of voltage-
      and [ATP]-dependent gating in these TTCs showed that: (a) Voltage- and [ATP]
      dependent gating of P2X2 requires binding of at least two ATP molecules. (b)
      D315A mutation in the beta-14 strand of the linker region connecting the ATP
      binding domains to the pore-forming helices induces two different gating modes;
      this requires the presence of the D315A mutation in at least two subunits. (c)
      The T339S mutation in the pore domains of all three subunits abolishes the
      voltage dependence of P2X2 gating in saturating [ATP], making P2X2 equally active
      at all membrane potentials. Increasing the number of T339S mutations in the TTC
      results in gradual changes in the voltage dependence of gating from that of the
      wild-type channel, suggesting equal and independent contributions of the subunits
      at the pore level. (d) Voltage- and [ATP]-dependent gating in TTCs differs
      depending on the location of one D315A relative to one K308A that blocks the ATP
      binding and downstream signal transmission. (e) Voltage- and [ATP]-dependent
      gating does not depend on where one T339S is located relative to K308A (or
      D315A). Our results suggest that each intersubunit ATP-binding signal is directly
      transmitted on the same subunit to the level of D315 via the domain that
      contributes K308 to the beta-14 strand. The signal subsequently spreads equally
      to all three subunits at the level of the pore, resulting in symmetric and
      independent contributions of the three subunits to pore opening. 

PMID- 24863934
TI  - Deinococcus radiodurans can interfere with quorum sensing by producing an AHL
      acylase and an AHL-lactonase.
AB  - Bacterial communication via the secretion of small diffusible compounds allows
      microorganisms to regulate gene expression in a coordinated manner. As many
      virulence traits are regulated in this fashion, disruption of chemical
      communication has been proposed as novel antimicrobial therapy. Quorum-quenching
      enzymes have been a promising discovery in this field as they interfere with the
      communication of Gram-negative bacteria. AHL-lactonases and AHL-acylases have
      been described in a variety of bacterial strains; however, usually only one of
      these two groups of enzymes has been described in a single species. We report
      here the presence of a member of each group of enzymes in the extremophile
      bacterium Deinococcus radiodurans. Co-occurrence of both enzymes in a single
      species increases the chance of inactivating foreign AHL signals under different
      conditions. We demonstrate that both enzymes are able to degrade the quorum
      sensing molecules of various pathogens subsequently affecting virulence gene
      expression. These studies add the quorum-quenching enzymes of D. radiodurans to
      the list of potent quorum-quenchers and highlight the idea that quorum quenching
      could have evolved in some bacteria as a strategy to gain a competitive advantage
      by altering gene expression in other species.

PMID- 24863933
TI  - Impact of detubulation on force and kinetics of cardiac muscle contraction.
AB  - Action potential-driven Ca(2+) currents from the transverse tubules (t-tubules)
      trigger synchronous Ca(2+) release from the sarcoplasmic reticulum of
      cardiomyocytes. Loss of t-tubules has been reported in cardiac diseases,
      including heart failure, but the effect of uncoupling t-tubules from the
      sarcolemma on cardiac muscle mechanics remains largely unknown. We dissected
      intact rat right ventricular trabeculae and compared force, sarcomere length, and
      intracellular Ca(2+) in control trabeculae with trabeculae in which the t-tubules
      were uncoupled from the plasma membrane by formamide-induced osmotic shock
      (detubulation). We verified disconnection of a consistent fraction of t-tubules
      from the sarcolemma by two-photon fluorescence imaging of FM4-64-labeled
      membranes and by the absence of tubular action potential, which was recorded by
      random access multiphoton microscopy in combination with a voltage-sensitive dye
      (Di-4-AN(F)EPPTEA). Detubulation reduced the amplitude and prolonged the duration
      of Ca(2+) transients, leading to slower kinetics of force generation and
      relaxation and reduced twitch tension (1 Hz, 30 degrees C, 1.5 mM [Ca(2+)]o). No
      mechanical changes were observed in rat left atrial trabeculae after formamide
      shock, consistent with the lack of t-tubules in rodent atrial myocytes.
      Detubulation diminished the rate-dependent increase of Ca(2+)-transient amplitude
      and twitch force. However, maximal twitch tension at high [Ca(2+)]o or in post
      rest potentiated beats was unaffected, although contraction kinetics were slower.
      The ryanodine receptor (RyR)2 Ca-sensitizing agent caffeine (200 uM), which
      increases the velocity of transverse Ca(2+) release propagation in detubulated
      cardiomyocytes, rescued the depressed contractile force and the slower twitch
      kinetics of detubulated trabeculae, with negligible effects in controls. We
      conclude that partial loss of t-tubules leads to myocardial contractile
      abnormalities that can be rescued by enhancing and accelerating the propagation
      of Ca(2+)-induced Ca(2+) release to orphan RyR2 clusters. 

PMID- 24863937
TI  - Exposure and preventive measure to reduce high and daily exposure to Bacillus
      thuringiensis in potted plant production.
AB  - The bacterium Bacillus thuringiensis (Bt) is the active organism in a variety of
      commercially available products used worldwide as biopesticides. Bt products are
      applied in large outdoor areas as well as in indoor environments. Even though it
      has been sold for decades, not much is known about the occupational exposure to
      Bt. The aim of this study was to obtain knowledge about the exposure to Bt
      subspecies israelensis (Bti) in a propagation section in a greenhouse, where Bti
      is applied hourly by a spray boom, and to test a preventive measure to reduce the
      exposure to airborne Bti. Furthermore, we wanted to study the exposure during
      work with potted plants treated earlier with Bti. Exposure to aerosols with Bti
      was measured repeatedly by personal and stationary samplers before and after the
      intervention. Bti was identified by polymerase chain reaction in air and soil
      samples. Personal exposure to inhalable Bti in the propagation section was
      3*10(5) cfu m(-3) (median level, n = 22); the personal exposure of people working
      with plants treated earlier with Bti was 3200 cfu m(-3) (median level, n = 17).
      The highest single measure was found for the person working with the spray boom
      (7*10(5) cfu m(-3)) but airborne Bti was present at all sampling stations in the
      propagation section. Bti constituted a high share of the airborne cultivable
      bacteria and a smaller share of the soilborne bacteria in the propagation
      section. In a human cell assay, spiking an aerosol sample with a product with Bti
      increased the inflammatory potential of an aerosol sample from the greenhouse
      significantly. Based on the inflammatory potential and the high personal
      exposure, a cover around the spray boom was built as an attempt to reduce the
      daily exposure to Bti. The cover reduced the personal exposure to Bti from
      3.0*10(5) cfu m(-3) to 1.8*10(4) cfu m(-3). The exposure was thus reduced by a
      factor 17, which is a considerable reduction. Bti was present in different
      particle size fractions with the majority, both before and after the
      intervention, in the fraction of airborne particles with an aerodynamic diameter
      between 1.2 and 3.0 um. The measured occupational exposure to Bti is discussed in
      relation to risk evaluation. 

PMID- 24863938
TI  - A novel in-frame 18-bp microdeletion in MT-CYB causes a multisystem disorder with
      prominent exercise intolerance.
AB  - A novel heteroplasmic mitochondrial DNA (mtDNA) microdeletion affecting the
      cytochrome b gene (MT-CYB) was identified in an Italian female patient with a
      multisystem disease characterized by sensorineural deafness, cataracts, retinal
      pigmentary dystrophy, dysphagia, postural and gait instability, and myopathy with
      prominent exercise intolerance. The deletion is 18-base pair long and encompasses
      nucleotide positions 15,649-15,666, causing the loss of six amino acids (Ile-Leu
      Ala-Met-Ile-Pro) in the protein, but leaving the remaining of the MT-CYB sequence
      in frame. The defective complex III function was cotransferred with mutant mtDNA
      in cybrids, thus unequivocally establishing its pathogenic role. Maternal
      relatives failed to show detectable levels of the deletion in blood and urinary
      epithelium, suggesting a de novo mutational event. This is the second report of
      an in-frame intragenic deletion in MT-CYB, which most likely occurred in early
      stages of embryonic development, associated with a severe multisystem disorder
      with prominent exercise intolerance. 

PMID- 24863939
TI  - The preventive effect of grape seed extract on artificial enamel caries
      progression in a microbial biofilm-induced caries model.
AB  - OBJECTIVES: The aim of this study was to evaluate the effect of grape seed
      extract (GSE) on enamel caries lesion formation in an in vitro Streptococcus
      mutans biofilm model. METHODS: Enamel fragments were prepared from bovine
      incisors and divided into six treatment groups (n=12): inoculated Brain Heart
      Infusion with 1% sucrose (BHIS), 1mg/mL GSE, 2mg/mL GSE, 3mg/mL GSE, 10ppm
      fluoride as NaF, and uninoculated BHIS. For biofilm formation, tooth fragments
      were incubated anaerobically in polystyrene 6-well tissue culture plates
      containing BHIS, the respective agents, and S. mutans (1*10(5)CFU/mL) for 24h at
      37 degrees C. Culture medium was replaced with fresh BHIS and respective agents
      daily over a 7-day period. Following caries lesion formation, lesion depth (LD)
      and relative optical density (ROD) were determined by polarized light microscopy
      (PLM) and confocal laser scanning microscopy (CLSM), respectively, to evaluate
      lesion progression. RESULTS: LDs of the 2mg/mL GSE group (122.86+/-13.41MUm) and
      the 3mg/mL GSE group (111.92+/-11.39MUm) were significantly smaller than those of
      the 1mg/mL GSE (198.33+/-17.70MUm) and control groups (210.86+/-15.50MUm)
      (p<0.05). Compared with the 2mg/mL and 3mg/mL groups, the control and 1mg/mL GSE
      groups showed significantly lower ROD values when depth was less than 200MUm,
      indicating greater mineral loss. CONCLUSIONS: Dose-dependent GSE inhibits in
      vitro enamel caries formation due to its ability to suppress growth of S. mutans
      and the formation of biofilm. CLINICAL SIGNIfiCANCE: Grape seed extract may be a
      novel virulence-targeted natural antimicrobial agent for caries prevention.

PMID- 24863940
TI  - A color-reaction-based rapid screening for null activity of
      butyrylcholinesterase: a step toward point-of-care screening for succinylcholine
      apnea.
AB  - Succinylcholine apnea happens in cases of null butyrylcholinesterase activity
      after administration of preintubation succinylcholine. So far, there is no such
      popular test that can rapidly screen null butyrylcholinesterase activity from
      plasma. Development of a novel method for rapid screening of null
      butyrylcholinesterase activity of plasma samples was the objective of the current
      work. Dichromate reagent was added to 1-naphthol, 2-naphthol, phenol, and para
      nitrophenol in separate aliquots and watched for the color formation. Plasma
      samples preincubated with and without selective butyrylcholinesterase inhibitor
      were mixed with 1-naphthylacetate and watched for color development after
      addition of dichromate reagent. Fitting of 1-naphthylacetate at the active site
      of butyrylcholinesterase was analyzed by using tools of computational biology. It
      was seen that 1-naphthol formed color with dichromate reagent in a concentration
      dependent manner. Other phenols did not form color with dichromate reagent even
      at 500-um concentrations. Plasma sample with and without selective
      butyrylcholinesterase inhibitor (tetra isopropyl pyrophosphoramide) was
      distinguishable by color formation when incubated with 1-naphthylacetate,
      followed by the addition of dichromate reagent. In silico analysis also showed
      that 1-naphthylacetate fitted well at the active site of butyrylcholinesterase.
      The developed method may be used for rapid screening for null
      butyrylcholinesterase activity at point of care. 

PMID- 24863941
TI  - Establishment and analysis of osteosarcoma cell sublines with different
      metastatic characteristics.
AB  - The aim of this study is to establish human osteosarcoma MG-63 cell sublines with
      different metastatic characteristics and provide good experimental models for
      mechanism study of osteosarcoma metastasis. Six cell sublines were screened and
      established by using the in vitro cloning technology. In vitro invasion
      experiments, cellular electrophoretic mobility determinations, cellular
      proliferation rate determinations, and soft agar clone formation assays were used
      to compare, analyze, and identify the metastatic characteristics of various cell
      sublines. The results indicated that the invasion capacity, cellular
      electrophoretic mobility, cell proliferation, and soft agar clone formation
      capacity of A2, A3, and A16 sublines were higher than those of A1, A6, and A20
      sublines. There was no significant difference in various values determined among
      A2, A3, and A16, and among A1, A6, and A20 (P > 0.05), but there were significant
      differences in various values determined between the former three and the latter
      three (P < 0.05). In conclusion, MG-63 cell sublines with different metastatic
      characteristics can be established by combining several technologies and can
      contribute to further research on the mechanism of osteosarcoma metastasis.

PMID- 24863942
TI  - MiR-122/Wnt/beta-catenin regulatory circuitry sustains glioma progression.
AB  - Malignant glioma is the most common type of human intracranial cancer and has
      poor prognosis due to its high recurrence and invasiveness. However, the
      molecular mechanisms underlying its malignant phenotypes have still not been
      completely explored yet. miR-122 has been well documented to act as a tumor
      suppressor for hepatocellular carcinoma and breast cancer, but the implication of
      miR-122 in the progression of glioma is not clear yet. In this study, we found
      that miR-122 was underexpressed in glioma specimens and glioma cell lines,
      compared with normal brain tissues and cell lines. The expression of miR-122
      levels is inversely correlated with the survival of patients after surgery.
      Overexpression of miR-122 by an adenoviral vector suppressed the proliferation
      and colony formation of glioma cells. The in vivo tumorigenicity of U-87 MG cells
      was also greatly compromised by restoring miR-122. miR-122 suppressed the
      activation of Wnt/beta-catenin pathway in glioma cells. Interestingly, Wnt/beta
      catenin signaling conversely reduced the expression of miR-122 in glioma cells,
      maybe in a hepatocyte nuclear factor (HNF)-dependent mechanism. Taken together,
      we revealed that there is a miR-122/Wnt/beta-catenin regulatory circuitry
      existing in glioma cells that contributes to glioma progression.

PMID- 24863943
TI  - A multigenic approach to evaluate genetic variants of PLCE1, LXRs, MMPs, TIMP,
      and CYP genes in gallbladder cancer predisposition.
AB  - Gallbladder cancer (GBC) is a violent neoplasm associated with late diagnosis,
      unsatisfactory treatment, and poor prognosis. The disease shows complex interplay
      between multiple genetic variants. We analyzed 15 polymorphisms in nine genes
      involved in various pathways to find out combinations of genetic variants
      contributing to GBC risk. The genes included in the study were matrix
      metalloproteinases (MMP-2, MMP-7, and MMP-9), tissue inhibitor of
      metalloproteinases (TIMP-2), cytochrome P450 (CYP)1A1, CYP1B1, phospholipase C
      epsilon 1 (PLCE1), liver X receptor (LXR)-alpha, and LXR-beta. Genotypes were
      determined by PCR-RFLP and TaqMan probes. Statistical analysis was done by SPSS
      version 16. Multilocus analysis was performed by Classification and Regression
      Tree (CART) analysis and multifactor dimensionality reduction (MDR) to gene-gene
      interactions in modifying GBC risk. In silico analysis was done using various
      bioinformatics tools (F-SNP, FAST-SNP). Single locus analysis showed association
      of MMP-2 (-735 C > T, -1306 C > T), MMP-7 - 181 A > G, MMP-9 (P574R, R668Q), TIMP
      2 - 418 G > C, CYP1A1-MspI, CYP1A1-Ile462Val, PLCE1 (rs2274223 A > G, rs7922612 T
      > C) and LXR-beta T > C (rs3546355 G > A, rs2695121 T > C) polymorphisms with GBC
      risk (p < 0.05) whereas CYP1B1 and LXR-alpha variants were not associated with
      GBC risk. Multidimensional reduction analysis revealed LXR-beta (rs3546355 G > A,
      rs2695121 T > C), MMP-2 (-1306 C > T), MMP-9 (R668Q), and PLCE1 rs2274223 A > G
      to be key players in GBC causation (p < 0.001, CVC = 7/10). The results were
      further supported by independent CART analysis (p < 0.001). In silico analysis of
      associated variants suggested change in splicing or transcriptional regulation.
      Interactome and STRING analysis showed network of associated genes. The study
      found PLCE1 and LXR-beta network interactions as important contributory factors
      for genetic predisposition in gallbladder cancer.

PMID- 24863944
TI  - Relationship between chemotherapy and prognosis in different subtypes of node
      negative breast cancer.
AB  - Knowledge is limited about the relationship between chemotherapy and prognosis
      among the subtypes of axillary node-negative breast cancer (ANNBC). In this
      study, a population including 2,236 primary and operable ANNBC patients, with a
      median age of 53, were included. All breast tumors were classified into five
      immunohistochemically defined subtypes-luminal A, luminal B, luminal human
      epidermal growth factor receptor 2 (HER2), HER2 overexpression, and triple
      negative. With a median follow-up of 73.6 months, the rate of relapse was lowest
      in luminal A (6.5 %) and highest in HER2 overexpression subtype (16.4 %).
      Multivariate analysis indicated that the risks of relapse and death were enhanced
      in HER2 overexpression and triple-negative (TN) subtypes, and these two subtypes
      were independent predictors of relapse and death. Luminal A patients with risk
      factors could benefit from chemotherapy in terms of relapse-free survival (RFS).
      The relapse rate of TN patients after chemotherapy with taxanes was lower
      compared with that after chemotherapy without taxanes. In conclusion, women with
      ANNBC were at higher risks of relapse and death if suffering from HER2
      overexpression or TN diseases. Chemotherapy could reduce the recurrence rate of
      luminal A patients with risk factors. TN patients may benefit from adjuvant
      chemotherapy containing taxanes.

PMID- 24863945
TI  - Diagnostic value of urine prostate cancer antigen 3 test using a cutoff value of
      35 MUg/L in patients with prostate cancer.
AB  - The aim of this study is to explore the diagnostic role of urine prostate cancer
      antigen 3 (PCA3) in detecting prostate cancer (PCa) through a systematic review
      and meta-analysis. Relevant research studies aiming at the application of urine
      PCA3 level in PCa diagnosis were searched in PubMed, Embase, Chinese Biomedical
      Database (CBM), Chinese National Knowledge Infrastructure (CNKI), VIP, and Wan
      Fang databases independently, which were published up to May 8, 2014. The pooled
      sensitivity, specificity, positive diagnostic likelihood ratio (DLR+), negative
      diagnostic likelihood ratio (DLR-), diagnostic odds ratio, and the area under the
      summary receiver operating characteristic were used to evaluate the value of
      urine PCA3 in diagnosis of PCa by using the Meta-DiSc and STATA 12.0 statistical
      software. Sixteen research studies with a total 2,457 PCa patients and 4,236
      control individuals were included in this meta-analysis. Overall, the results
      showed sensitivity and specificity of urine PCA3 in the diagnosis of PCa was 0.57
      (95 % CI = 0.55-0.59), and 0.71 (95 % CI = 0.70-0.73), respectively. The DLR +
      and PLR - in the diagnosis of PCa were 2.12 (95 % CI = 1.89-2.38), and 0.55 (95 %
      CI = 0. 50-0.61), respectively. The pooled diagnostic odds ratio was 3.93 (95 %
      CI = 3.28-4.72). The area under the curve (AUCs) and *Q index estimate were
      0.7118 and 0.6623, respectively. Urine PCA3 is a potential biomarker for the
      diagnosis of PCa. However, further well-designed studies with large samples will
      be needed to confirm the results got from present meta-analysis.

PMID- 24863946
TI  - No evidence of correlation between p53 codon 72 G > C gene polymorphism and
      cancer risk in Indian population: a meta-analysis.
AB  - p53 is a tumor suppressor gene, which is activated in response to several forms
      of cellular stress and exerts multiple antiproliferative functions, making it the
      most frequent target for genetic alteration in cancer. Various studies have
      evaluated the association between p53 codon 72 G > C (rs1042522) polymorphism and
      risk of cancer. However, results from the published studies remained
      inconclusive. The aim of this study is to investigate the precise association
      between this variant and a risk of cancer in a large-scale meta-analysis. We
      searched the PubMed (MEDLINE) and Google Scholar web databases for studies
      regarding the association of p53 codon 72 G > C polymorphism and risk of cancer
      in the Indian population. Pooled odds ratio (OR) with 95 % confidence interval
      (CI) were calculated by using random effect model to assess the association.
      Twenty studies with 3,258 cancer cases and 4,260 healthy controls were included.
      Overall, no significant association was detected for C allele carrier (C vs. G:
      OR = 1.135, 95 % CI = 0.930 to 1.386, p = 0.211) and homozygous (CC vs. GG: OR =
      1.200, 95 % CI = 0.810 to 1.779, p = 0.364), heterozygous (CG vs. GG: OR = 1.204,
      95 % CI = 0.921 to 1.575, p = 0.175), dominant (CC + CG vs. GG: OR = 1.231, 95 %
      CI = 0.932 to 1.625, p = 0.144), and recessive (CC vs. GG + GC: OR = 1.078, 95 %
      CI = 0.792 to 1.468, p = 0.632) genetic models, respectively. No significant
      publication bias was observed by using Begg's funnel plot and Egger's test.
      Present meta-analysis indicated that the p53 codon 72 G > C polymorphism was not
      associated with cancer risk. This suggests that this polymorphism may not be an
      independent risk factor for cancer in the Indian population.

PMID- 24863947
TI  - S100A2 protein and non-small cell lung cancer. The dual role concept.
AB  - S100A2 is a member of the EF-hand motif family S100. Its role has been recently
      implicated in carcinogenesis and metastasis. Although its precise role in NSCLC
      patients is debated and conflicting results have been published, it has been
      associated with patient survival. S100A2 expression was downregulated in some
      studies while others disagree that S100A2 is strongly expressed in lung cancer.
      It has been recently published by Hountis et al. that there is a significant
      association between nuclear S100A2 positivity and better disease-free interval.
      Intensity of expression was the highest in the early and advanced stages, and
      equally distributed in the middle stages. This is indicative for a dual role of
      this protein in carcinogenesis. The expression of S100A2 in operable NSCLC varies
      widely, and this differential location and expression pattern (nuclear or
      cytoplasmic or both) seem to correlate with prognosis. The precise role for the
      movement of S100A2 protein between cytoplasm and nucleus is still unclear. We
      present here a literature review, and we propose the dual concept on its
      substantial role as a prognostic or predictive indicator in this unfavorable
      group of patients. 

PMID- 24863948
TI  - Prediction of thyroid extracapsular extension with cervical lymph node metastases
      (ECE-LN) by CEUS and BRAF expression in papillary thyroid carcinoma.
AB  - The aim of our study was to find a specific imaging (contrast-enhanced
      ultrasound, CEUS) to detect extracapsular extension and cervical lymph node
      metastases (ECE-LNM) that associated with BRAF protein expression in papillary
      thyroid carcinoma (PTC). Preoperative utrasonography (US) or CEUS was performed
      in the diagnosis of extracapsular extension (ECE) in 317 patients with 369 PTC.
      BRAF protein status was tested on the primary tumor and lymph node involvement.
      The diagnostic accuracy of CEUS and US was evaluated after thyroid surgery. The
      association between CEUS and BRAF expression were then analyzed to investigate
      the diagnostic value of ECE-LNM in PTC. The sensitivity and specificity of CEUS
      were higher than those in US in the diagnosis of ECE in patients with PTC (91.1,
      86.5 vs 49, 55 %). BRAF protein overexpression were significantly associated with
      ECE (P = 0.0003) and lymph node metastasis (LNM) positive cases (P = 0.0014). The
      results of CEUS, not US, have a significant correlation with BRAF expression
      status in PTC samples (P < 0.0001). Associated with BRAF protein expression
      status, the routine preoperative CEUS could have a good value in the diagnosis of
      ECE-LNM in PTC and facilitate a surgeon to improve further clinical management.

PMID- 24863950
TI  - An original arthroscopic fixation of adult's tibial eminence fractures using the
      Tightrope(r) device: a report of 8 cases and review of literature.
AB  - PURPOSE: The objective of this study is to asset the efficiency of the use of the
      Tightrope(r) device to treat isolated tibial spine fractures in adults. METHODS:
      All patients treated for isolated tibial spine fracture between November 2007 and
      February 2011 have been retrospectively included. The main judgment criteria was
      the post-operative knee laxity measured by Rolimeter(r) (Aircast) and the
      secondary criteria were the IKDC scores, the knee mobility, the Lachman test and
      the bone union. 8 patients have been included. The mean age was 34.2 years (+/-
      12.5). The classification of Meyers and McKeever identified 5 types II, 2 types
      IIIa and 1 type IIIb. The mean follow-up period was 10 months. RESULTS: The mean
      post-operative anterior knee laxity was 6 +/- 2.14 mm for the operated side and
      5.6 +/- 1.85 mm for the opposite side. No significant difference was found
      (P=0.73). According to the IKDC classification 3 patients were normal (A), 2 were
      nearly normal (B), 1 was abnormal (C) and 1 was very abnormal (D). The mean IKDC
      subjective score was 70.71 +/- 17.56. All 8 fractures achieved union without
      elevation. 3 patients developed motion complications and 2 required an
      arthroscopic arthrolysis. No other significant complication was noted. The
      outcome was compared to the different series published during the last 10 years.
      CONCLUSION: The use of the Tightrope(r) device is a simple technique occurring a
      rigid fixation, allowing early rehabilitation with a high rate of arthrofibrosis.
      LEVEL OF EVIDENCE: Level IV, case series.

PMID- 24863949
TI  - Study to determine the durability of glycaemic control with early treatment with
      a vildagliptin-metformin combination regimen vs. standard-of-care metformin
      monotherapy-the VERIFY trial: a randomized double-blind trial.
AB  - AIMS: Durability of good glycaemic control (HbA1c ) is of importance as it can be
      the foundation for delaying diabetic complications. It has been hypothesized that
      early initiation of treatment with the combination of oral anti-diabetes agents
      with complementary mechanisms of action can increase the durability of glycaemic
      control compared with metformin monotherapy followed by a stepwise addition of
      oral agents. Dipeptidyl peptidase-4 inhibitors are good candidates for early use
      as they are efficacious in combination with metformin, show weight neutrality and
      a low risk of hypoglycaemia. We aimed to test the hypothesis that early combined
      treatment of metformin and vildagliptin slows beta-cell deterioration as measured
      by HbA1c . METHODS: Approximately 2000 people with Type 2 diabetes mellitus who
      were drug-naive or who were treated with metformin for less than 1 month, and who
      have HbA1c of 48-58 mmol/mol (6.5-7.5%), will be randomized in a 1:1 ratio in
      VERIFY, a 5-year multinational, double-blind, parallel-group study designed to
      compare early initiation of a vildagliptin-metformin combination with standard-of
      care initiation of metformin monotherapy, followed by the stepwise addition of
      vildagliptin when glycaemia deteriorates. Further deterioration will be treated
      with insulin. The primary analysis for treatment failure will be from a Cox
      proportional hazard regression model and the durability of glycaemic control will
      be evaluated by assessing treatment failure rate and the rate of loss in
      glycaemic control over time as co-primary endpoints. SUMMARY: VERIFY is the first
      study to investigate the long-term clinical benefits of early combination
      treatment vs. the standard-of-care metformin monotherapy with a second agent
      added by threshold criteria.

PMID- 24863951
TI  - Recursive confidence band construction for an unknown distribution function.
AB  - Given a sample X1,...,Xn of independent observations from an unknown continuous
      distribution function F, the problem of constructing a confidence band for F is
      considered, which is a fundamental problem in statistical inference. This
      confidence band provides simultaneous inferences on all quantiles and also on all
      of the cumulative probabilities of the distribution, and so they are among the
      most important inference procedures that address the issue of multiplicity. A
      fully nonparametric approach is taken where no assumptions are made about the
      distribution function F. Historical approaches to this problem, such as
      Kolmogorov's famous () procedure, represent some of the earliest inference
      methodologies that address the issue of multiplicity. This is because a
      confidence band at a given confidence level 1-alpha allows inferences on all of
      the quantiles of the distribution, and also on all of the cumulative
      probabilities, at that specified confidence level. In this paper it is shown how
      recursive methodologies can be employed to construct both one-sided and two-sided
      confidence bands of various types. The first approach operates by putting bounds
      on the cumulative probabilities at the data points, and a recursive integration
      approach is described. The second approach operates by providing bounds on
      certain specified quantiles of the distribution, and its implementation using
      recursive summations of multinomial probabilities is described. These recursive
      methodologies are illustrated with examples, and R code is available for their
      implementation. 

PMID- 24863952
TI  - Therapeutic apheresis in renal transplantation; current practices.
AB  - Apheresis is an important treatment modality for the removal of pathologic
      antibodies and circulating proteins in kidney transplantation. The use of
      apheresis has been shown to be a necessary preconditioning component in ABO
      incompatible kidney transplant. Removal of pathologic anti-A and anti-B
      antibodies has been accomplished with a variety of apheresis modalities including
      plasma exchange, fractional plasma exchange, and immunoabsorption techniques.
      Using these modalities in conjunction with potent modern immunosuppression, ABO
      incompatible kidney transplants have achieved graft and patient survivals similar
      to that seen in ABO compatible transplants. Apheresis has also been an important
      modality in the removal of anti-human leukocyte antigen (HLA) antibodies both for
      the purposes of desensitization and treatment of antibody mediated rejection of
      the kidney. Although good randomized controlled trials are lacking in the
      treatment of acute antibody mediated rejection, most treatment regimens include
      the use of apheresis as an essential component for reduction of anti-HLA antibody
      titers. Similarly, a variety of desensitization protocols have been developed to
      allow highly sensitized kidney transplant candidates to be successfully
      transplanted in the presence of donor-specific HLA antibodies. Most of these
      protocols involve apheresis to improve the removal of pathologic antibodies.
      Finally, aphereis has been used with mixed success for the treatment of recurrent
      focal segmental glomerulosclerosis. Evidence indicates that in some cases a
      circulating factor exists which apheresis can remove and ameliorate the nephrotic
      proteinuria.

PMID- 24863953
TI  - Prevalence of unrecognized heart failure in older persons with shortness of
      breath on exertion.
AB  - AIMS: The majority of patients with heart failure are diagnosed in primary care,
      but underdiagnosis is common. Shortness of breath is a prevalent complaint of
      older persons and one of the key symptoms of heart failure. We assessed the
      prevalence of unrecognized heart failure in elderly patients presenting to
      primary care with shortness of breath on exertion. METHODS AND RESULTS: This was
      a cross-sectional selective screening study. Patients aged 65 years or over
      presenting to primary care with shortness of breath on exertion in the previous
      12 months were eligible when not known to have an established, echocardiographic
      confirmed diagnosis of heart failure. All participants underwent history taking,
      physical examination, electrocardiography, and a blood test of N-terminal pro B
      type natriuretic peptide (NTproBNP). Only those with an abnormal
      electrocardiogram or NTproBNP level exceeding the exclusionary cut-point for non
      acute onset heart failure (>15 pmol/L (~125 pg/mL) underwent open-access
      echocardiography. An expert panel established presence or absence of heart
      failure according to the criteria of the European Society of Cardiology heart
      failure guidelines. The mean age of the 585 participants was 74.1 (SD 6.3) years,
      and 54.5% were female. In total, 92 (15.7%, 95% CI 12.9-19.0) participants had
      heart failure: 17 (2.9%, 95% CI 1.8-4.7) had heart failure with a reduced
      ejection fraction (<=45%), 70 (12.0%, 95% CI 9.5-14.9) had heart failure with
      preserved ejection fraction, and five (0.9%, 95% CI 0.3-2.1) had isolated right
      sided heart failure. CONCLUSION: Elderly primary care patients with shortness of
      breath on exertion often have unrecognized heart failure, mainly with preserved
      ejection fraction.

PMID- 24863954
TI  - Effect of a patient-directed discharge letter on patient understanding of their
      hospitalisation.
AB  - BACKGROUND/AIM: Poor patient understanding of their diagnosis and treatment plan
      can adversely impact clinical outcome following hospital discharge. Discharge
      summaries are primarily written for the doctor rather than the patient. We
      determined patient understanding of the reasons for hospitalisation, in-hospital
      tests, treatments and post-discharge recommendations, and whether a brief patient
      directed discharge letter (PADDLE) delivered during a brief discussion prior to
      discharge would improve understanding. METHODS: A prospective randomised
      controlled trial was conducted, including 67 hospitalised patients. After a
      baseline questionnaire, patients were randomised to receive the PADDLE letter or
      usual care. Those receiving the letter had an immediate follow-up questionnaire.
      Patient understanding was compared with a summary letter written by the treating
      clinician, using a 5-point Likert scale ranging from none to full understanding.
      A questionnaire was administered at 3 and 6 months. RESULTS: At baseline,
      patients had almost full understanding (median score 4) of reasons for
      hospitalisation and treatments. However, despite high self-appraisal, patients
      objectively had very little understanding of tests performed and post-discharge
      recommendations (median 2). Those receiving the letter had an immediate increase
      to almost full understanding (median 4) of tests performed (P < 0.001) and to
      full understanding (median 5) of post-discharge recommendations. This increase
      did not persist at 3 or 6 months. CONCLUSIONS: A simple patient-directed letter
      delivered during a brief discussion improves patient understanding of their
      hospitalisation and post-discharge recommendations, which is otherwise limited.
      Further evaluation of this brief and well-received intervention is indicated,
      with the goal of improving patient understanding, satisfaction and clinical
      outcomes.

PMID- 24863955
TI  - Fusion of Golgi-derived vesicles mediated by SNAP-25 is essential for sympathetic
      neuron outgrowth but relatively insensitive to botulinum neurotoxins in vitro.
AB  - Sympathetic neurons ramify to innervate multiple cells in target tissues. In
      compartmentalized cultures of rat superior cervical ganglion neurons, cleavage of
      synaptosomal-associated protein of Mr  = 25 000 (SNAP-25) in neurites exposed to
      botulinum neurotoxin type A (BoNT/A) arrested their growth and collapsed
      interstitial branches, but this required large, nonclinical doses. A protease
      inactive mutant proved ineffective, confirming involvement of SNAP-25 in neurite
      extension and arborization. BoNT/C1 acted like BoNT/A, but BoNT/E caused only
      mild inhibition, likely due to transient SNAP-25 proteolysis. Near-total lack of
      susceptibility to BoNT/B or BoNT/D revealed that vesicle-associated membrane
      protein (VAMPs) isoforms 1-3 are not essential. Neurite length was not reduced
      when either BoNT/A or BoNT/C1 was applied to the somata, with no detrimental
      effect on neuron viability being observed. Treatments that protect cells from
      deprivation of nerve growth factor failed to prevent the toxin-induced loss of
      neurites. Inactivation of SNAP-25 caused the accumulation at neurite branch sites
      of Golgi-derived organelles labelled with N-(4,4-difluoro-5,7-dimethyl-4-bora
      3a,4a-diaza-s-indacene-3-pentanoyl)-sphingosine conjugated to bovine serum
      albumin, prior to the collapse of arbors. Notably, neurite growth was ~ 1000-fold
      less susceptible to BoNT/A than cholinergic transmission in these neurons.
      Accordingly, a BoNT/A acceptor synaptic vesicle protein 2 (SV2) was found to be
      colocalized with VAMP 1-3, but not with VAMP 7, which is implicated in the growth
      of neurites. In conclusion, neurites depend on SNAP-25 for extension but this is
      quite resistant to BoNT/A, possibly, because of a low density of SV2 at growth
      sites that are distant from the highly susceptible regions of neurotransmitter
      release. 

PMID- 24863956
TI  - An assessment of goal-free evaluation: case studies of four goal-free
      evaluations.
AB  - This article provides a descriptive review of four goal-free program evaluations
      (GFE). GFE is an evaluation model where the independent evaluator is
      intentionally screened from the program's stated goals and objectives in hopes of
      reducing potential goal-related tunnel vision. The findings from these GFE case
      studies are focused in three areas: (1) elements of the programs that were
      evaluated and their existing evaluation contexts (e.g., pre-evaluation
      conditions, size of evaluation budget), (2) design of the GFEs (e.g., screening
      method, data collection methods), and (3) expertise of the goal-free evaluators
      (e.g., training, degrees attained). The findings indicate that, when employed,
      GFE is used as a qualitative data collection method; and the GFEs conducted have
      been relatively small in size and scope. The conclusions are that a more explicit
      operationalization of GFE is needed for increased use, and that systematic and
      empirical study comparing GFE with other evaluation models is warranted. 

PMID- 24863957
TI  - Development of a framework to measure health profession regulation strengthening.
AB  - This paper describes the development of a framework to evaluate the progress and
      impact of a multi-year US government initiative to strengthen nursing and
      midwifery professional regulation in sub-Saharan Africa. The framework was
      designed as a capability maturity model, which is a stepwise series of
      performance levels that describe the sophistication of processes necessary to
      achieve an organization's objectives. A model from the field of software design
      was adapted to comprise the key functions of a nursing and midwifery regulatory
      body and describe five stages of advancing each function. The framework was used
      to measure the progress of five countries that received direct assistance to
      strengthen regulations and to benchmark the status of regulations in the 17
      countries participating in the initiative. The framework captured meaningful
      advancements in regulatory strengthening in the five supported countries and the
      level of regulatory capacity in participating countries. The project uses the
      framework to assess yearly progress of supported countries, track the overall
      impact of the project on national and regional nursing regulation, and to
      identify national and regional priorities for regulatory strengthening. It is the
      first of its kind to document and measure progress toward sustainably
      strengthening nursing and midwifery regulation in Africa. 

PMID- 24863958
TI  - Multifunctional 8-hydroxyquinoline-appended cyclodextrins as new inhibitors of
      metal-induced protein aggregation.
AB  - Mounting evidence suggests a pivotal role of metal imbalances in protein
      misfolding and amyloid diseases. As such, metal ions represent a promising
      therapeutic target. In this context, the synthesis of chelators that also contain
      complementary functionalities to combat the multifactorial nature of
      neurodegenerative diseases is a highly topical issue. We report two new 8
      hydroxyquinoline-appended cyclodextrins and highlight their multifunctional
      properties, including their Cu(II) and Zn(II) binding abilities, and capacity to
      act as antioxidants and metal-induced antiaggregants. In particular, the latter
      property has been applied in the development of an effective assay that exploits
      the formation of amyloid fibrils when beta-lactoglobulin A is heated in the
      presence of metal ions. 

PMID- 24863959
TI  - Fetal skeletal dysplasias in a tertiary care center: radiology, pathology, and
      molecular analysis of 112 cases.
AB  - Fetal skeletal dysplasias are a heterogeneous group of rare genetic disorders,
      affecting approximately 2.4-4.5 of 10,000 births. We performed a retrospective
      review of the perinatal autopsies conducted between the years 2002-2011 at our
      center. The study population consisted of fetuses diagnosed with skeletal
      dysplasia with subsequent termination, stillbirth and live-born who died shortly
      after birth. Of the 2002 autopsies performed, 112 (5.6%) were diagnosed with
      skeletal dysplasia. These 112 cases encompassed 17 of 40 groups of Nosology 2010.
      The two most common Nosology groups were osteogenesis imperfecta [OI, 27/112
      (24%)] and the fibroblast growth factor receptor type 3 (FGFR3) chondrodysplasias
      [27/112 (24%)]. The most common specific diagnoses were thanatophoric dysplasia
      (TD) type 1 [20 (17.9%)], and OI type 2 [20 (17.9%)]. The combined radiology,
      pathology, and genetic investigations and grouping the cases using Nosology 2010
      resulted in a specific diagnosis in 96 of 112 cases. 

PMID- 24863960
TI  - Hypercoagulability, D-dimer and atrial fibrillation: an overview of biological
      and clinical evidence.
AB  - Atrial fibrillation (AF) is the most common among the severe cardiac arrhythmias
      and carries a significant risk of mortality and morbidity in the general
      population. The most important complication is represented by development of one
      or more thrombi in the left atrium of the dyskinetic heart, and their successive
      cerebral and peripheral embolization. The pathophysiological basis of the
      thromboembolic complications in AF entails the presence of a hypercoagulable
      state, which is mirrored by increased concentrations of a variety of
      prothrombotic markers. D-dimer is universally considered the gold standard among
      the various biomarkers that reflect activation of coagulation, fibrinolysis, or
      both, and several studies have assessed its diagnostic and prognostic role in AF.
      With a few exceptions and despite a broad heterogeneity in the study designs,
      published data seem to demonstrate that D-dimer values may be associated with the
      presence of atrial thrombosis, may be predictive of primary adverse outcomes and
      death, may be correlated with cerebral infarction volume, and may also be a
      useful parameter for assessing the degree of hypercoagulability of AF patients
      after cardioversion. If larger prospective studies confirm these findings, D
      dimer assessment may hence become an integral part of the clinical decision
      making in patients with AF.

PMID- 24863961
TI  - Could trisialotransferrin be used as an additional biomarker to CDT in order to
      improve detection of chronic excessive alcohol intake?
AB  - OBJECTIVES: Carbohydrate-deficient transferrin is a well-known biomarker widely
      used for detection of chronic excessive alcohol intake. However, under certain
      clinical conditions particularly frequently met amongst heavy drinkers
      (steatosis, fibrosis, cirrhosis...), it isn't a reliable biomarker. In this
      study, we tried to find additional biomarkers to CDT in order to improve
      detection of chronic excessive alcohol intake. DESIGN AND METHODS: We conducted a
      retrospective cohort study from December 2007 to December 2009. We focused mainly
      on three different groups: heavy drinking patients with active alcohol
      consumption (n=243), cirrhotic patients (abstinent patients and non alcoholic
      cirrhosis, n=44) and control group (n=85). RESULTS: In our study, CDT showed a
      poor sensitivity for diagnosis of heavy drinking patients (around 63%, and even
      lower) for cirrhotic patients and patients at advanced stage of fibrosis.
      Combination of CDT with trisialotransferrin enabled to improve significantly
      sensitivity and specificity (p-value AUC ROC<0.001). When adding mean corpuscular
      volume and gamma-glutamyltransferase to this first combination, performances were
      even better (p-value<0.001). This second cluster enabled to make a statistically
      significant difference between cirrhotic patients with active alcohol consumption
      compared to abstinent cirrhotic patients and to non alcoholic cirrhotic patients
      (p-value<0.001). CONCLUSION: From our study, trisialotransferrin seems to be a
      useful additional biomarker to CDT in order to improve detection of chronic
      excessive alcohol intake.

PMID- 24863962
TI  - A patient with a high concentration of B-type natriuretic peptide (BNP) but
      normal N-terminal proBNP concentration: A case report.
AB  - OBJECTIVES: A 61-year-old female presented with non-typical chest pain. High
      levels of plasma B-type natriuretic peptide (BNP; result 3188 ng/L, reference
      range<100 ng/L, method Abbott Architect) were found, although she did not exhibit
      dyspnoea or other clinical symptoms of heart failure. Echocardiography did not
      provide an explanation for the elevated BNP concentrations. In follow-up, the
      chest pain complaints disappeared but BNP remained elevated at the same levels.
      The serum N-terminal proBNP (NT-proBNP) concentration appeared to be normal. This
      led us to doubt the accuracy of the BNP values. DESIGN AND METHODS: Possible
      interference was investigated with BNP and NT-proBNP assays from different
      manufacturers, various (auto)antibody tests, sample dilutions, addition of mouse
      serum and polyethylene glycol (PEG) precipitation. RESULTS: BNP and NT-proBNP
      concentrations were normal when measured using all other (NT-pro)BNP
      immunoassays. Serial dilutions of sample and addition of mouse serum did not
      alter the results. Specific (auto)antibody tests were negative. However, PEG
      precipitation showed the presence of a high molecular weight immunoreactive
      protein. CONCLUSIONS: We report a false positive BNP result possibly caused by a
      macro-BNP. This macro-BNP was only immunoreactive in the Abbott Architect BNP
      immunoassay. Clinicians should be aware of analytical interference when BNP
      results are constantly elevated in the absence of (non)cardiac causes.

PMID- 24863963
TI  - Extent of differences in dental caries in permanent teeth between childhood and
      adulthood in 26 countries.
AB  - OBJECTIVE: To compare levels of caries in permanent teeth between children and
      adults and specifically, the extent to which the decayed, missing, filled teeth
      (DMFT) index was greater in adults than in children. METHODS: The analysis was
      based on published reports from 26 countries with comparable summary data on
      dental caries for different World Health Organisation index ages. Reports were
      obtained from two large electronic databases, the World Health Organisation Oral
      Health Country/Area Profile Programme and the Global Burden of Disease 2010
      Study. RESULTS: Very much higher levels of caries occurred in adults than in
      children in all 26 countries. For most countries, irrespective of the DMFT levels
      in 12-year-olds, the percentage difference in levels of DMFT between 12-year-olds
      and 35- to 44-year-olds was above 500% and the relative difference was 5 or more.
      CONCLUSION: Large differences in experience of dental caries in permanent teeth
      were found between childhood and adulthood.

PMID- 24863964
TI  - Age-dependent dopaminergic dysfunction following fetal exposure to atrazine in SD
      rats.
AB  - The herbicide, atrazine (ATR), is used worldwide and its contamination in the
      environment has resulted in documented human exposure. It has also been shown
      that ATR results in dopaminergic neurotoxicity, however, few studies have
      investigated the long-term effects of ATR following in utero exposure. Therefore,
      we evaluated the effects of ATR exposure in Sprague Dawley rats during
      gestational on the offspring dopaminergic system development. Pregnant dams were
      treated with oral ATR at 0, 25, 50 mg/kg/day from gestational day 0 to postnatal
      day 1. In this study, we examined the hypothesis that ATR could cross the
      placental barrier and have long-term adverse effects on the synthesis,
      degradation and reuptake of DA in the brain. For this purpose,we examine the
      concentration of levodopa (L-DA), dopamine (DA), 3,4-dihydroxyphenylacetic acid
      (DOPAC), and homovanillic acid (HVA) in stratum. The mRNA and protein expression
      of orphan nuclear hormone (Nurr1), tyrosine hydroxylase(TH), vesicular
      monoaminetransporter 2 (VMAT2), dopamine transporter (DAT), monoamine (MAO), and
      catechol-O-methyl transferase (COMT) in the midbrain were examined by
      fluorescence PCR and Western blot when the offspring reached six-month old or one
      year old .When measured 6 months post-treatment, the level of DA and expression
      of Nurr1, VMAT2, DAT and TH were reduced in the striatum and Substantia nigra,
      respectively.

PMID- 24863965
TI  - Lipopolysaccharide-induced microRNA-146a targets CARD10 and regulates
      angiogenesis in human umbilical vein endothelial cells.
AB  - This aim of this study was to explore the role of miRNA-146a (miR-146a) and its
      target genes in endothelial cells. We demonstrated that lipopolysaccharide (LPS)
      induced the upregulation of miR-146a in human umbilical vein endothelial cells
      (HUVECs), and that the induction was blocked by silencing toll-like receptors,
      the adaptor molecule MyD88, and the nonspecific NF-kappaB inhibitor BAY 11-7082.
      In addition, knockdown of miR-146a by transfection of the locked nucleic acid
      antimiR-146a significantly inhibited LPS-induced cell migration and tube
      formation. A combined analysis of bioinformatics miRanda algorithms and a whole
      genome expression microarray of immunoprecipitated Ago2 ribonucleoprotein
      complexes identified 14 potential target genes. Subsequent transfection with the
      miR-146a precursor pre-miR-146a into HUVECs validated that CARD10 was the target
      gene of the miR-146a, both at the mRNA and protein levels. Silencing CARD10
      inhibited p65 nuclear translocation in the cells receiving LPS stimulation and
      increased angiogenesis. Therefore, miR-146a may play a role in regulating the
      angiogenesis in HUVECs by downregulating CARD10, which acts in a negative
      feedback regulation loop to inhibit the activation of NF-kappaB that normally
      impairs angiogenesis. 

PMID- 24863966
TI  - Response to Hunt et al., invalid controls undermine conclusions of FDA studies.

PMID- 24863967
TI  - Phenobarbital-mediated tumor promotion in transgenic mice with humanized CAR and
      PXR.
AB  - The nuclear receptors CAR (constitutive androstane receptor) and possibly PXR
      (pregnane X receptor) mediate the hepatic effects of phenobarbital (PB) and
      similar-acting compounds. Although PB is a potent nongenotoxic tumor promoter in
      rodent liver, epidemiological data from epilepsy patients treated with
      phenobarbital do not show a specific role of PB in human liver cancer risk. That
      points to species differences in the susceptibility to tumor promotion by PB,
      which might be attributed to divergent functions of the PB receptors CAR and PXR
      in mice and humans. In the present study, male transgenic mice expressing human
      CAR and PXR were used to detect possible differences between wild-type (WT) and
      humanized mice in their response to CAR activation in a tumor
      initiation/promotion experiment with a single injection of the tumor initiator N
      nitrosodiethylamine preceding chronic PB treatment for 10 months. Analysis of
      liver tumor burden revealed that PB strongly promoted the outgrowth of
      hepatocellular adenoma driven by activated beta-catenin in WT mice, whereas the
      tumor-promoting effect of PB was much less pronounced in the humanized group. In
      conclusion, the present findings demonstrate that human CAR and PXR support tumor
      promotion by PB in mouse liver, but to a significantly lesser extent than the WT
      murine receptors. 

PMID- 24863968
TI  - Target organ specific activity of drosophila MRP (ABCC1) moderates developmental
      toxicity of methylmercury.
AB  - Methylmercury (MeHg) is a ubiquitous and persistent neurotoxin that poses a risk
      to human health. Although the mechanisms of MeHg toxicity are not fully
      understood, factors that contribute to susceptibility are even less well known.
      Studies of human gene polymorphisms have identified a potential role for the
      multidrug resistance-like protein (MRP/ABCC) family, ATP-dependent transporters,
      in MeHg susceptibility. MRP transporters have been shown to be important for MeHg
      excretion in adult mouse models, but their role in moderating MeHg toxicity
      during development has not been explored. We therefore investigated effects of
      manipulating expression levels of MRP using a Drosophila development assay.
      Drosophila MRP (dMRP) is homologous to human MRP1-4 (ABCC1-4), sharing 50%
      identity and 67% similarity with MRP1. A greater susceptibility to MeHg is seen
      in dMRP mutant flies, demonstrated by reduced rates of eclosion on MeHg
      containing food. Furthermore, targeted knockdown of dMRP expression using
      GAL4>UAS RNAi methods demonstrates a tissue-specific function for dMRP in gut,
      Malpighian tubules, and the nervous system in moderating developmental
      susceptibility to MeHg. Using X-ray synchrotron fluorescence imaging, these same
      tissues were also identified as the highest Hg-accumulating tissues in fly
      larvae. Moreover, higher levels of Hg are seen in dMRP mutant larvae compared
      with a control strain fed an equivalent dose of MeHg. In sum, these data
      demonstrate that dMRP expression, both globally and within Hg-targeted organs,
      has a profound effect on susceptibility to MeHg in developing flies. Our findings
      point to a potentially novel and specific role for dMRP in neurons in the
      protection against MeHg. Finally, this experimental system provides a tractable
      model to evaluate human polymorphic variants of MRP and other gene variants
      relevant to genetic studies of mercury-exposed populations. 

PMID- 24863969
TI  - Mechanism of action of lung damage caused by a nanofilm spray product.
AB  - Inhalation of waterproofing spray products has on several occasions caused lung
      damage, which in some cases was fatal. The present study aims to elucidate the
      mechanism of action of a nanofilm spray product, which has been shown to possess
      unusual toxic effects, including an extremely steep concentration-effect curve.
      The nanofilm product is intended for application on non-absorbing flooring
      materials and contains perfluorosiloxane as the active film-forming component.
      The toxicological effects and their underlying mechanisms of this product were
      studied using a mouse inhalation model, by in vitro techniques and by
      identification of the binding interaction. Inhalation of the aerosolized product
      gave rise to increased airway resistance in the mice, as evident from the
      decreased expiratory flow rate. The toxic effect of the waterproofing spray
      product included interaction with the pulmonary surfactants. More specifically,
      the active film-forming components in the spray product, perfluorinated
      siloxanes, inhibited the function of the lung surfactant due to non-covalent
      interaction with surfactant protein B, a component which is crucial for the
      stability and persistence of the lung surfactant film during respiration. The
      active film-forming component used in the present spray product is also found in
      several other products on the market. Hence, it may be expected that these
      products may have a toxicity similar to the waterproofing product studied here.
      Elucidation of the toxicological mechanism and identification of toxicological
      targets are important to perform rational and cost-effective toxicological
      studies. Thus, because the pulmonary surfactant system appears to be an important
      toxicological target for waterproofing spray products, study of surfactant
      inhibition could be included in toxicological assessment of this group of
      consumer products. 

PMID- 24863971
TI  - Mansonella ozzardi in the municipality of Tefe, Amazonas, Brazil, 60 years after
      the first report: an epidemiologic study.
AB  - The prevalence of mansonelliasis was studied in the municipality of Tefe, state
      of Amazonas, Brazil. The prevalence (thick blood smear method) was 13.6%
      (147/1,078), higher in the Solimoes River region (16.3%) than in the Tefe River
      region (6.3%). In the sampled communities in the Solimoes River region, a higher
      density of cases was observed, as indicated by a kernel analysis (odds ratio
      0.34; 95% confidence interval: 0.20-0.57). Males had a higher prevalence (chi2 =
      31.292, p < 0.001) than women. Mansonella ozzardi prevalence was higher in
      retirees and farmers (28.9% and 27%, respectively). Prevalence also significantly
      increased with age (chi2 = -128.17, p < 0.001), with the highest numbers
      occurring in persons older than 67 years.

PMID- 24863972
TI  - Large indoor cage study of the suppression of stable Aedes aegypti populations by
      the release of thiotepa-sterilised males.
AB  - The sterile insect technique (SIT) is a promising pest control method in terms of
      efficacy and environmental compatibility. In this study, we determined the
      efficacy of thiotepa-sterilised males in reducing the target Aedes aegypti
      populations. Treated male pupae were released weekly into large laboratory cages
      at a constant ratio of either 5:1 or 2:1 sterile-to-fertile males. A two-to-one
      release ratio reduced the hatch rate of eggs laid in the cage by approximately a
      third and reduced the adult catch rate by approximately a quarter, but a 5:1
      release drove the population to elimination after 15 weeks of release. These
      results indicate that thiotepa exposure is an effective means of sterilising Ae.
      aegypti and males thus treated are able to reduce the reproductive capacity of a
      stable population under laboratory conditions. Further testing of the method in
      semi-field enclosures is required to evaluate the mating competitiveness of
      sterile males when exposed to natural environmental conditions. If proven
      effective, SIT using thiotepa-sterilised males may be incorporated into an
      integrated programme of vector control to combat dengue in Cuba. 

PMID- 24863974
TI  - Inferences about the global scenario of human T-cell lymphotropic virus type 1
      infection using data mining of viral sequences.
AB  - Human T-cell lymphotropic virus type 1 (HTLV-1) is mainly associated with two
      diseases: tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM) and
      adult T-cell leukaemia/lymphoma. This retrovirus infects five-10 million
      individuals throughout the world. Previously, we developed a database that
      annotates sequence data from GenBank and the present study aimed to describe the
      clinical, molecular and epidemiological scenarios of HTLV-1 infection through the
      stored sequences in this database. A total of 2,545 registered complete and
      partial sequences of HTLV-1 were collected and 1,967 (77.3%) of those sequences
      represented unique isolates. Among these isolates, 93% contained geographic
      origin information and only 39% were related to any clinical status. A total of
      1,091 sequences contained information about the geographic origin and viral
      subtype and 93% of these sequences were identified as subtype "a". Ethnicity data
      are very scarce. Regarding clinical status data, 29% of the sequences were
      generated from TSP/HAM and 67.8% from healthy carrier individuals. Although the
      data mining enabled some inferences about specific aspects of HTLV-1 infection to
      be made, due to the relative scarcity of data of available sequences, it was not
      possible to delineate a global scenario of HTLV-1 infection. 

PMID- 24863970
TI  - Three rare diseases in one Sib pair: RAI1, PCK1, GRIN2B mutations associated with
      Smith-Magenis Syndrome, cytosolic PEPCK deficiency and NMDA receptor glutamate
      insensitivity.
AB  - The National Institutes of Health Undiagnosed Diseases Program evaluates patients
      for whom no diagnosis has been discovered despite a comprehensive diagnostic
      workup. Failure to diagnose a condition may arise from the mutation of genes
      previously unassociated with disease. However, we hypothesized that this could
      also co-occur with multiple genetic disorders. Demonstrating a complex syndrome
      caused by multiple disorders, we report two siblings manifesting both similar and
      disparate signs and symptoms. They shared a history of episodes of hypoglycemia
      and lactic acidosis, but had differing exam findings and developmental courses.
      Clinical acumen and exome sequencing combined with biochemical and functional
      studies identified three genetic conditions. One sibling had Smith-Magenis
      Syndrome and a nonsense mutation in the RAI1 gene. The second sibling had a de
      novo mutation in GRIN2B, which resulted in markedly reduced glutamate potency of
      the encoded receptor. Both siblings had a protein-destabilizing homozygous
      mutation in PCK1, which encodes the cytosolic isoform of phosphoenolpyruvate
      carboxykinase (PEPCK-C). In summary, we present the first clinically
      characterized mutation of PCK1 and demonstrate that complex medical disorders can
      represent the co-occurrence of multiple diseases. 

PMID- 24863977
TI  - Anthropophilic Anopheles species composition and malaria in Tierradentro,
      Cordoba, Colombia.
AB  - Malaria is still a primary health problem in Colombia. The locality of
      Tierradentro is situated in the municipality of Montelibano, Cordoba, in the
      northwest of Colombia, and has one of the highest annual parasite index of
      malaria nationwide. However, the vectors involved in malaria transmission in this
      locality have not yet been identified. In this study, the local anthropophilic
      Anopheles composition and natural infectivity with Plasmodium were investigated.
      In August 2009, 927 female Anopheles mosquitoes were collected in eight
      localities using the human landing catch method and identified based on their
      morphology. Cryptic species were determined by restriction fragment length
      polymorphism-internal transcribed spacer (ITS)2 molecular analysis. Eight species
      [Anopheles nuneztovari s.l. (92.8%), Anopheles darlingi (5.1%), Anopheles
      triannulatus s.l. (1.8%), Anopheles pseudopunctipennis s.l. (0.2%), Anopheles
      punctimacula s.l. (0.2%), Anopheles apicimacula (0.1%), Anopheles albimanus
      (0.1%) and Anopheles rangeli (0.1%)] were identified and species identity was
      confirmed by ITS2 sequencing. This is the first report of An. albimanus, An.
      rangeli and An. apicimacula in Tierradentro. Natural infectivity with Plasmodium
      was determined by ELISA. None of the mosquitoes was infectious for Plasmodium.
      An. nuneztovari s.l. was the predominant species and is considered the primary
      malaria vector; An. darlingi and An. triannulatus s.l. could serve as secondary
      vectors.

PMID- 24863976
TI  - Risk of symptomatic dengue for foreign visitors to the 2014 FIFA World Cup in
      Brazil.
AB  - Brazil will host the FIFA World CupTM, the biggest single-event competition in
      the world, from June 12-July 13 2014 in 12 cities. This event will draw an
      estimated 600,000 international visitors. Brazil is endemic for dengue. Hence,
      attendees of the 2014 event are theoretically at risk for dengue. We calculated
      the risk of dengue acquisition to non-immune international travellers to Brazil,
      depending on the football match schedules, considering locations and dates of
      such matches for June and July 2014. We estimated the average per-capita risk and
      expected number of dengue cases for each host-city and each game schedule chosen
      based on reported dengue cases to the Brazilian Ministry of Health for the period
      between 2010-2013. On the average, the expected number of cases among the 600,000
      foreigner tourists during the World Cup is 33, varying from 3-59. Such risk
      estimates will not only benefit individual travellers for adequate pre-travel
      preparations, but also provide valuable information for public health
      professionals and policy makers worldwide. Furthermore, estimates of dengue cases
      in international travellers during the World Cup can help to anticipate the
      theoretical risk for exportation of dengue into currently non-infected areas. 

PMID- 24863980
TI  - Anatomical mapping of the nasal muscles and application to cosmetic surgery.
AB  - We present an anatomical mapping of the most important muscles influencing the
      nose, incorporating constant anatomical structures, and their spatial
      correlations. At our disposal were the midfaces of 18 bodies of both sexes,
      obtained by informed consent from body donors aged between 60 and 80 years.
      Macroscopically, we dissected the nasal regions of eight corpses, six midfaces
      were prepared according to plastination histology, four by creating plastinated
      slices. On their way from their periosteal origin to the edge of the skin, the
      muscles of the nose cross the subcutaneous adipose tissue, dividing it into
      superficial and deep layers. The individual muscle fibers insert into the skin
      directly at the reticular corium. Sometimes, they reach the border of the
      epidermis which represents a special arrangement of corial muscle attachments.
      The course of the anatomical fibers of individual nasal muscles presented
      macroscopically and microscopically in this study offers surgeons a detailed
      overview of the anatomically important muscular landmarks of the midface.

PMID- 24863981
TI  - 4-Benzofuranyloxynicotinamide derivatives are novel potent and orally available
      TGR5 agonists.
AB  - A series of 4-benzofuranyloxynicotinamide derivatives were identified to be
      novel, potent, and orally available TGR5 agonists. Among them, compound 9r had
      the highest potency in vitro (hTGR5 EC50 = 0.28 nM, mTGR5 EC50 = 0.92 nM).
      Further in vivo studies disclosed that 9r could effectively lower the blood
      glucose, but meantime caused an increase in the gallbladder volume of mice.
      Subsequent research toward eliminating the gallbladder toxicity resulted in
      compound 19 with low permeability. Although the EC50 of mTGR5 of 19 was larger
      one order than that of 9r, it still had good glucose-lowing activity.
      Nevertheless, 19 also caused the adverse effects to the gallbladder. The drug
      levels detection disclosed that the concentration of 19 was only lower than that
      of 9r in plasma but was higher in bile and gallbladder tissue. This result
      indicated that low exposure in plasma could not guarantee low exposure in bile
      and gallbladder tissue, and thus resulting in the gallbladder toxicity of 19.

PMID- 24863979
TI  - Host genetic factors in American cutaneous leishmaniasis: a critical appraisal of
      studies conducted in an endemic area of Brazil.
AB  - American cutaneous leishmaniasis (ACL) is a vector-transmitted infectious disease
      with an estimated 1.5 million new cases per year. In Brazil, ACL represents a
      significant public health problem, with approximately 30,000 new reported cases
      annually, representing an incidence of 18.5 cases per 100,000 inhabitants. Corte
      de Pedra is in a region endemic for ACL in the state of Bahia (BA), northeastern
      Brazil, with 500-1,300 patients treated annually. Over the last decade,
      population and family-based candidate gene studies were conducted in Corte de
      Pedra, founded on previous knowledge from studies on mice and humans.
      Notwithstanding limitations related to sample size and power, these studies
      contribute important genetic biomarkers that identify novel pathways of disease
      pathogenesis and possible new therapeutic targets. The present paper is a
      narrative review about ACL immunogenetics in BA, highlighting in particular the
      interacting roles of the wound healing gene FLI1 with interleukin-6 and genes
      SMAD2 and SMAD3 of the transforming growth factor beta signalling pathway. This
      research highlights the need for well-powered genetic and functional studies on
      Leishmania braziliensis infection as essential to define and validate the role of
      host genes in determining resistance/susceptibility regarding this disease. 

PMID- 24863982
TI  - Synthesis and in vitro antitumor activity of novel 2-alkyl-5-methoxycarbonyl-11
      methyl-6H-pyrido[4,3-b]carbazol-2-ium and 2-alkylellipticin-2-ium chloride
      derivatives.
AB  - Twenty-one types of novel ellipticine derivatives and pyridocarbazoles (5
      methoxycarbonyl-11-methyl-6H-pyrido[4,3-b]carbazoles) with a nitrosourea moiety,
      linked by an oxydiethylene unit at the 2 position, were synthesized, and their
      cytotoxicity against HeLa S-3 cells was evaluated. Some of these new compounds
      exhibited potent antitumor activity by comparison with that of ellipticine. 

PMID- 24863983
TI  - Drainage of pleural effusion in mechanically ventilated patients: time to measure
      chest wall compliance?
AB  - PURPOSE: Pleural effusion (PE) is commonly encountered in mechanically
      ventilated, critically ill patients and is generally addressed with evacuation or
      by fluid displacement using increased airway pressure (P(AW)). However, except
      when massive or infected, clear evidence is lacking to guide its management. The
      aim of this study was to investigate the effect of recruitment maneuvers and
      drainage of unilateral PE on respiratory mechanics, gas exchange, and lung
      volume. MATERIALS AND METHODS: Fifteen critically ill and mechanically ventilated
      patients with unilateral PE were enrolled. A 3-step protocol (baseline,
      recruitment, and effusion drainage) was applied to patients with more than 400 mL
      of PE, as estimated by chest ultrasound. Predefined subgroup analysis compared
      patients with normal vs reduced chest wall compliance (C(CW)). Esophageal and
      P(AW)s, respiratory system, lung and C(CW)s, arterial blood gases, and end
      expiratory lung volumes were recorded. RESULTS: In the whole case mix, neither
      recruitment nor drainage improved gas exchange, lung volume, or tidal mechanics.
      When C(CW) was normal, recruitment improved lung compliance (81.9 [64.8-104.1] vs
      103.7 [91.5-111.7] mL/cm H2O, P < .05), whereas drainage had no significant
      effect on total respiratory system mechanics or gas exchange, although it
      measurably increased lung volume (1717 vs 2150 mL, P < .05). In the setting of
      reduced C(CW), however, recruitment had no significant effect on total
      respiratory system mechanics or gas exchange, whereas pleural drainage improved
      respiratory system and C(CW)s as well as lung volume (42.7 [38.9-50.0] vs 47.0
      [43.8-63.3], P < .05 and 97.4 [89.3-97.9] vs 126.7 [92.3-153.8] mL/cm H2O, P <
      .05 and 1580 vs 1750 mL, P < .05, respectively). CONCLUSIONS: Drainage of a
      moderate-sized effusion should not be routinely performed in unselected
      population of critically ill patients. We suggest that measurement of C(CW) may
      help in the decision-making process.

PMID- 24863985
TI  - Urinary tract infection and vesicoureteral reflux in children with mild antenatal
      hydronephrosis.
AB  - OBJECTIVE: The postnatal management of mild antenatal hydronephrosis (ANH)
      remains controversial. The purpose of this study was to evaluate the incidence of
      UTI and VUR in children with mild ANH in order to determine the necessity of
      antibiotic prophylaxis (ABP) and VCUG. METHOD: The data of 1511 patients with
      various grades of ANH who were referred to Department of Urology, Boston
      Children's Hospital between January 1998 and January 2010 were reviewed and 760
      patients who had mild ANH were identified. The inclusion criteria were: 1) A
      confirmed report of ANH or actual prenatal ultrasound (US) images. 2) Postnatal
      evaluation and management conducted at the hospital. 3) Persistent mild
      hydronephrosis on the first US done between two weeks and three months of age. 4)
      No other US findings such as ureteral dilatation, duplication anomalies or
      bladder abnormalities. 5) At least one three-month follow up. Univariate
      statistical analysis was performed using a Student's t test. RESULTS: Of the 760
      patients who were identified, 608 (80%) were males, and 225 (30%) had bilateral
      mild hydronephrosis. Of these, 475 patients (63%) underwent an initial screening
      VCUG. VUR was identified in 13 patients (1.7%) with grades varying from 1 to 5.
      At follow up, hydronephrosis resolved in 67% of the renal units and worsened in
      3.3%. Among the 692 patients with available follow-up data, 23 (3.3%) had a
      documented UTI. Twelve of these children had an initial screening VCUG that was
      negative for VUR. Of these 12 patients, seven underwent a subsequent RNC with
      none having VUR; five of the 12 patients did not undergo a repeat evaluation for
      VUR (four had a UTI after the screening VCUG and one had an afebrile UTI). Eleven
      of the 23 children with mild ANH did not have an initial screening VCUG, and all
      underwent a subsequent VCUG/RNC. Only two children were then found to have VUR
      Grade 4-5. CONCLUSION: The incidence of UTI and VUR in children with mild ANH is
      low. Consequently, routine VCUG screening for VUR and the use of long-term ABP is
      not necessary for all patients with asymptomatic mild AHN. Evaluation for VUR in
      children with mild ANH should be reserved for those who subsequently present with
      a UTI.

PMID- 24863984
TI  - Feasibility of using CT volume as a predictor of specimen weight in a subgroup of
      patients with low risk Wilms tumors registered on COG Study AREN03B2:
      implications for central venous catheter placement.
AB  - OBJECTIVE: Patients with stage I Wilms tumor, age <= 2 years, tumor <= 550 g may
      not require therapy beyond nephrectomy. This study's aims were to determine: (1)
      if a linear relationship exists between tumor weight and computed tomography (CT)
      estimated volume; (2) describe the accuracy of a slope-intercept equation in
      estimating weight; and (3) determine the potential impact of weight estimation on
      port placement decisions. MATERIALS AND METHODS: Tumor weight and port placement
      information were abstracted from 105 patients, age <= 2 years, with tumors +/-
      550 g, enrolled in COG AREN03B2. One radiologist estimated tumor size from CT
      scan. Prolate ellipse volume (PEV) was calculated, linear regression performed,
      slope-intercept equation calculated, equation estimated weight determined, and
      potential impact of the on port placement evaluated. RESULTS: A strong
      relationship exists between PEV and weight (R(2) = 0.87). The slope-intercept
      equation for weight was: weight = 1.04(PEV) + 58.75. Overall median relative
      error for the equation was 0.9%, and -3% in tumors weighing 350-750 g. Fifty-five
      ports were placed, 29 in patients with tumor weight <= 550 g, and six not placed
      in patients with tumor weight > 550 g. CONCLUSIONS: The relationship between PEV
      and weight produced a reliable weight prediction equation. Preoperative
      consideration of specimen weight may diminish the number of ports placed in this
      population.

PMID- 24863986
TI  - Indiana pouch in children: a 15-year experience.
AB  - OBJECTIVE: We report our experience with the Indiana pouch (continent urinary
      reservoir) in 12 consecutive children over the last 15 years and report their
      follow-up. MATERIAL AND METHODS: Twelve consecutive children, who underwent the
      continent urinary reservoir procedure in the form of an Indiana pouch, were
      prospectively enrolled in the study. All consecutive children who were referred
      to our service with multiple failed surgeries for exstrophy-epispadias repair,
      cloacal exstrophy, genitourinary rhabdomyosarcoma with residual disease in the
      trigonal area not amenable to partial cystectomy, and neuropathic bladder with
      nephrogenic metaplasia were included over the period 1997-2012. All these
      children were offered the same form of bladder substitution (Indiana pouch) as
      described by the Indiana group many years ago. Postoperative care was on a fixed
      protocol, and follow-up details recorded over the years. They were followed up
      for dry interval with clean intermittent catheterisation, social acceptance, and
      early and late complications. RESULTS: Out of these 12 patients (7 males and 5
      females), eight patients had exstrophy-epispadias with multiple failed operations
      carried out elsewhere, cloacal exstrophy (2), residual rhabdomyosarcoma in the
      trigonal area with incontinence following chemotherapy (1), and neuropathic
      bladder with recurrent diffuse neoplastic polyposis (1). In the follow-up period
      of 1-15 years (median 24 months) all the patients had a dry interval of 4 h or
      more with clean intermittent catheterisation. One patient had wound dehiscence
      during the postoperative period and another required stomal revision 1 year after
      initial surgery. CONCLUSIONS: The Indiana pouch is a reliable, safe, and
      effective form of bladder substitution. It can be reconstructed in a wide range
      of lower urinary tract disorders. In the vast majority of children with multiple
      failed surgical procedures for exstrophy-epispadias, the Indiana pouch is a safe,
      reliable, and reproducible procedure to provide a socially acceptable quality of
      life with a dry interval of 4 h.

PMID- 24863987
TI  - [The economic-financial crisis and health in Spain. Evidence and viewpoints.
      SESPAS report 2014].
AB  - The objectives of the SESPAS 2014 Report are as follows: a) to analyze the impact
      of the economic crisis on health and health-related behaviors, on health
      inequalities, and on the determinants of health in Spain; b) to describe the
      changes in the Spanish health system following measures to address the crisis and
      assess its potential impact on health; c) to review the evidence on the health
      impact of economic crises in other countries, as well as policy responses; and d)
      to suggest policy interventions alternative to those carried out to date with a
      population health perspective and scientific evidence in order to help mitigate
      the impact of the economic downturn on health and health inequalities. The report
      is organized in five sections: 1) the economic, financial and health crisis:
      causes, consequences, and contexts; 2) the impact on structural determinants of
      health and health inequalities; 3) the impact on health and health-related
      behaviors, and indicators for monitoring; 4) the impact on health systems; and 5)
      the impact on specific populations: children, seniors, and immigrants. There is
      some evidence on the relationship between the crisis and the health of the
      Spanish population, health inequalities, some changes in lifestyle, and
      variations in access to health services. The crisis has impacted many structural
      determinants of health, particularly among the most vulnerable population groups.
      Generally, policy responses on how to manage the crisis have not taken the
      evidence into account. The crisis may contribute to making public policy
      vulnerable to corporate action, thus jeopardizing the implementation of healthy
      policies. 

PMID- 24863988
TI  - [Cuts, austerity and health. SESPAS report 2014].
AB  - Since 2009, the economic recession has led to cuts in spending on social welfare
      policy and in health care. The most important risks to health depend on negative
      changes in social determinants. Notable among these determinants are unemployment
      and the large proportion of people at risk of poverty, which affects 30% of
      children younger than 14 years. Social inequalities have increased significantly,
      much more than health inequalities, probably because the value of retirement
      pensions has been maintained until now. Most of the population is fairly
      satisfied with the public health system, although it is under considerable
      pressure. Mortality statistics have not been affected so far, but there has been
      an increase in mood disorders and mental health problems. Health services
      utilization has decreased and the number of publicly prescribed drugs has fallen
      dramatically. This restriction accounts for much of the decrease in public
      spending on health, since the hospital care budget has not decreased, despite the
      fall in primary care and public health spending. The crisis could encourage
      community health and the inclusion of health in all policies. It is the
      responsibility of professionals and public health institutions monitoring the
      trend in health problems and their determinants to avoid irreversible situations
      as far as possible. 

PMID- 24863989
TI  - [Lessons from abroad. Current and previous crisis in other countries. SESPAS
      report 2014].
AB  - The evidence available on the impact of previous crises on health reveals
      different patterns attributable to study designs, the characteristics of each
      crisis, and other factors related to the socioeconomic and political context.
      There is greater consensus on the mediating role of government policy responses
      to financial crises. These responses may magnify or mitigate the adverse effects
      of crises on population health. Some studies have shown a significant
      deterioration in some health indicators in the context of the current crisis,
      mainly in relation to mental health and communicable diseases. Alcohol and
      tobacco use have also declined in some European countries. In addition, this
      crisis is being used by some governments to push reforms aimed at privatizing
      health services, thereby restricting the right to health and healthcare.
      Specifically, action is being taken on the three axes that determine health
      system financing: the population covered, the scope of services, and the share of
      the costs covered. These measures are often arbitrarily implemented based on
      ideological decisions rather than on the available evidence and therefore adverse
      consequences are to be expected in terms of financial protection, efficiency, and
      equity. 

PMID- 24863990
TI  - [The Spanish economic crisis and its consequences on social spending. SESPAS
      report 2014].
AB  - This article offers a brief summary of the factors that the author believes
      should be considered when analyzing the multiple interrelations between the
      economic crisis and its effects on public finances, social spending, and the
      health and welfare of Spaniards. For the sake of brevity, a linear argument is
      followed, with the basic contents of the message, leaving some of the more
      controversial issues whose interpretation may be heavily influenced by ideology
      to the discussion. The core of the argument is that, despite the double dip of
      the Spanish recession, healthcare has survived the consequences of the crisis
      fairly well. This is particularly the case when the situation is analyzed in
      terms of the share of public expenditure to GDP and in per capita terms, given
      the evolution of these ratios, although the final effect is unknown in terms of
      the actual and potential beneficiaries. This relatively low incidence so far on
      the health of Spaniards is basically due to family networks, pooling their
      incomes, and to the acceptance by Spanish health professionals of budget cuts,
      which have allowed services and their apparent quality to be maintained,
      contrasting with private employment and public finances. Obviously, this is not a
      guarantee of sustainability unless economic growth recovers. Even if the Spanish
      economy and public finances improve, the composition of health care delivery
      needs to be reevaluated to achieve a new allocation between public and private
      responsibilities for healthcare in accordance with the social development of the
      21st century.

PMID- 24863991
TI  - [Vertical social mobility in Spain and ways to improve it. SESPAS report 2014].
AB  - In this article, we analyze the extent to which an individual's socioeconomic
      status is inherited and how equality of opportunity could be increased to improve
      social mobility. Poverty and deprivation can stop being dynastic-like if the
      social elevator works. In Spain, income inequality, measured by the Gini
      coefficient, rose from 0.31 in 2006 to 0.35 in 2012 (moving away from Scandinavia
      and Central Europe and more closely resembling income inequality in the UK or the
      United States), while the degree of intergenerational mobility is half-way
      between that in Italy and the United States. To change this situation and make
      the social elevator work, primary education should be improved and the health
      system should be steered toward primary healthcare. This will not be feasible
      without an improvement in politics and the institutional framework that determine
      these factors. 

PMID- 24863992
TI  - [Economic crisis and employment conditions: gender differences and the response
      of social and employment policies. SESPAS report 2014].
AB  - The economic crisis has had an impact across the European Union (EU), but has had
      a devastating impact on the labor market in Spain, which has become the country
      within the EU-15 with the worst employment indicators. The situation is worse in
      younger people, half of whom were unemployed in 2012, with a slightly higher rate
      in men (54.4%) than in women (51.8%). This high unemployment rate will be even
      more difficult to redress because of the decrease in public spending on active
      employment per percentage point of unemployment in 2012 compared with 2007.
      Furthermore, the decrease in spending on passive employment policies will worsen
      the health of the unemployed population. 

PMID- 24863993
TI  - [Impact of the crisis on the relationship between housing and health. Policies
      for good practice to reduce inequalities in health related to housing
      conditions].
AB  - Housing conditions can impact on physical and mental health through 4
      interrelated dimensions: 1) the home (the emotional housing conditions), 2) the
      physical housing conditions, and 3) the physical environment, and 4) the social
      (community) environment of the neighborhood where the house is located. In Spain,
      the use of the construction market as an engine for economic growth and the
      promotion of private property as the main type of housing tenure has led to the
      use of housing as a speculative good instead of its being considered a first
      necessity good. While Spain is the Organisation for Economic Co-operation and
      Development (OECD) country with the largest housing stock per inhabitant, this
      stock is highly underutilized, thus excluding the most deprived sector of the
      population from access to housing. The impact of the current economic crisis on
      housing has mainly been due to a reduction in household income, which has
      increased the number of families or persons struggling to cover their housing
      costs or being evicted. Evidence indicates that this type of problem has a
      negative impact on health, especially on mental health, but financial problems
      also make it difficult to meet other basic needs such as eating. There are
      several instruments to reduce the impact of the economic crisis, such as debt
      financing or deed of assignment in payment. In the long-term, the creation of a
      social housing stock should be promoted, as well as rental assistance mechanisms.

PMID- 24863995
TI  - [Impact of the economic crisis on the right to a healthy diet. SESPAS report
      2014].
AB  - The present article analyzes the impact of the economic crisis on food
      consumption in Spain, the most affected social profiles, and the consequences of
      changing patterns of food consumption on health. This article is based on
      official reports and previous empirical studies. The crisis has affected diet and
      food consumption. Families are attempting to spend less money on food. Food
      insecurity is rising and the most affected groups are those spending a higher
      proportion of their income on food. Cuts in food spending run parallel with
      unhealthy eating habits that encourage obesity. Consequently, the crisis
      contributes to undermining the right to a healthy diet, recognized by the
      International Covenant on Economic, Social and Cultural Rights of the United
      Nations. 

PMID- 24863994
TI  - [Trends in environmental risks in the context of the economic crisis. SESPAS
      report 2014].
AB  - This article aims to analyze the impact of the economic and financial crisis on
      environmental determinants of health. The World Health Organization estimates
      that between 13% and 27% of the disease burden in countries could be prevented by
      improving the environment. These effects are larger in vulnerable populations,
      especially among the poorest. In the last decade, outdoor air pollution (the most
      significant environmental health risk in most European countries) has declined,
      mostly due to the European policy of reducing emissions and to the decrease in
      activity following the economic crisis. During the last few years, this
      improvement in air quality has occurred simultaneously with a reduction in
      investment in environmental protection and could therefore be offset in the
      medium-term. The economic crisis has not reduced the trend for higher
      temperatures in Spain and Europe because climate change is a global phenomenon
      that is not directly related to local emissions. To reduce the risk of an
      increase in the health impact of environmental factors, certain key aspects
      should be considered, such as the need to maintain or develop adequate monitoring
      and control systems and the opportunity to implement policies that help improve
      the quality of the environment and reduce the vulnerability of different
      population groups in a cross-disciplinary framework of transparency and citizen
      participation. 

PMID- 24863996
TI  - [Changes in the regulation and government of the health system. SESPAS report
      2014].
AB  - The economic and fiscal crisis of 2008 has erupted into the debate on the
      sustainability of health systems; some countries, such as Spain, have implemented
      strong policies of fiscal consolidation and austerity. The institutional
      framework and governance model of the national health system (NHS) after its
      devolution to regions in 2002 had significant weaknesses, which were not apparent
      in the rapid growth stage but which have been clearly visible since 2010. In this
      article, we describe the changes in government regulation from the national and
      NHS perspective: both general changes (clearly prompted by the economic
      authorities), and those more specifically addressed to healthcare. The Royal
      Decree-Law 16/2012 represents the centerpiece of austerity policies in healthcare
      but also implies a rupture with existing political consensus and a return to
      social security models. Our characterization of austerity in healthcare explores
      impacts on savings, services, and on the healthcare model itself, although the
      available information only allows some indications. The conclusions highlight the
      need to change the path of linear, rapid and radical budget cuts, providing a
      time-frame for implementing key reforms in terms of internal sustainability; to
      do so, it is appropriate to restore political and institutional consensus, to
      emphasize "clinical management" and divestment of inappropriate services
      (approach to the medical profession and its role as micro-manager), and to create
      frameworks of good governance and organizational innovations that support these
      structural reforms.

PMID- 24863997
TI  - [Privatization in healthcare management: an adverse effect of the economic crisis
      and a symptom of bad governance. SESPAS report 2014].
AB  - It is often asserted that public management of healthcare facilities is
      inefficient. On the basis of that unproven claim, it is argued that privatization
      schemes are needed. In this article we review the available evidence, in Spain
      and other countries, on the application of private management mechanisms to
      publicly funded systems similar to the Spanish national health system. The
      evidence suggests that private management of healthcare services is not
      necessarily better than public management, nor vice versa. Ownership-whether
      public or private-of health care centers does not determine their performance
      which, on the contrary, depends on other factors, such as the workplace culture
      or the practice of suitable monitoring by the public payer. Promoting competition
      among centers (irrespective of the specific legal form of the management
      arrangements), however, could indeed lead to improvements under some
      circumstances. Therefore, it is advisable to cease the narrow-minded debate on
      the superiority of one or other model in order to focus on improving healthcare
      services management per se. Understanding that good governance affects health
      policies, the management of health care organizations, and clinical practice is,
      undoubtedly, an essential requirement but may not necessarily lead to policies
      that stimulate the solvency of the system. 

PMID- 24863998
TI  - [Austerity policies and changes in healthcare use patterns. SESPAS report 2014].
AB  - This article analyzes the main changes in healthcare use patterns in Spain
      related to the economic recession and to the measures taken to address it. The
      impact of the reform of drug copayment is examined; the number of prescriptions
      has decreased, although the effects of this reform on adherence, access to
      necessary and effective treatments, and health, are still unknown. This article
      also describes how waiting times and waiting lists for surgery have increased in
      recent years, as has the population's dissatisfaction with the national health
      system. Analysis of microdata from the Spanish national health surveys for 2006
      and 2011/12 show that the economic recession is deterring the use of uncovered
      dental visits among the lowest social class. We recommend clearer definition of
      the role played by copayments within the national health system, and focussing on
      those who most need healthcare in order to prevent the more socioeconomically
      advantaged collectives from consuming a larger share of available services after
      the cuts. 

PMID- 24863999
TI  - [Economic crisis and communicable diseases. SESPAS report 2014].
AB  - Past economic crises have increased the impact of communicable diseases
      especially on groups particularly vulnerable to the social and health
      consequences of the recession. However, it has been shown that the impact of
      these crises largely depends on the response of governments and the inhabitants
      of affected countries. We describe the consequences of the current crisis in the
      causal chain of infectious disease, including the response of the health system,
      and explore whether there is evidence of its impact in Spain. It is assumed that
      the possible effect of the crisis on living and working conditions is due to
      individual and social debt coupled with high unemployment as defining features of
      the crisis. We highlight the potential negative consequences of healthcare cuts
      on vulnerable populations, which have been partly excluded with the recent reform
      of health coverage. We compare mortality and morbidity data between two periods:
      before and after 2008, integrating, where possible, observed trends and
      institutional reports. Overall, no effect on infectious disease has been detected
      so far, although some signs of worsening, which could be compatible with the
      effects of the crisis, have been observed and need to be monitored and confirmed.
      We review the limitations of data sources that may not be sufficiently sensitive
      or up-to-date to detect changes that may require a latency period to become
      manifest. Instead of cutting resources, surveillance of these diseases should be
      improved, and an equitable social health response, which targets the population
      most affected by the crisis, should be guaranteed. 

PMID- 24864000
TI  - [Sexual and reproductive health and the economic crisis in Spain. SESPAS report
      2014].
AB  - Sexual and reproductive health (SRH) is protected by the public authorities to
      ensure that people enjoy a free, satisfying, and safe sexual life. Despite the
      approval of the National Sexual and Reproductive Health Strategy in 2011, the
      progress achieved may be jeopardized by recent proposals for legislative changes
      affecting this area (abortion Law and 16/2012 Law) and by the impact of the
      current economic crisis. This article aims to describe the current situation of
      sexual and reproductive health in the Spanish population and to identify the
      potential impact of the economic crisis. To this end, we used the following
      information sources: the National Sexual Health Survey, the DAPHNE surveys,
      births and fetal deaths statistics from the Spanish National Institute of
      Statistics, the Registry of Voluntary Pregnancy Interruptions, reports from the
      National Epidemiology Center, and the National AIDS Registry. Sexual health and
      the availability of information are rated as good by the Spanish population.
      Among young people, schools and health services have become less important as
      information sources and the internet has become more important. Since the
      beginning of the crisis, contraceptive use and fertility have declined and
      maternity has been delayed. The economic crisis seems to have affected some
      indicators of sexual and reproductive health. However, the potential effects on
      other indicators should continue to be monitored because insufficient time may
      have passed for accurate determination of the full effect of the crisis. 

PMID- 24864001
TI  - [Indicators to monitor the evolution of the economic crisis and its effects on
      health and health inequalities. SESPAS report 2014].
AB  - The economic crisis has adverse effects on determinants of health and health
      inequalities. The aim of this article was to present a set of indicators of
      health and its determinants to monitor the effects of the crisis in Spain. On the
      basis of the conceptual framework proposed by the Commission for the Reduction of
      Social Health Inequalities in Spain, we searched for indicators of social,
      economic, and political (structural and intermediate) determinants of health, as
      well as for health indicators, bearing in mind the axes of social inequality
      (gender, age, socioeconomic status, and country of origin). The indicators were
      mainly obtained from official data sources published on the internet. The
      selected indicators are periodically updated and are comparable over time and
      among territories (among autonomous communities and in some cases among European
      Union countries), and are available for age groups, gender, socio-economic
      status, and country of origin. However, many of these indicators are not
      sufficiently reactive to rapid change, which occurs in the economic crisis, and
      consequently require monitoring over time. Another limitation is the lack of
      availability of indicators for the various axes of social inequality. In
      conclusion, the proposed indicators allow for progress in monitoring the effects
      of the economic crisis on health and health inequalities in Spain. 

PMID- 24864002
TI  - [Economic crisis, poverty and childhood. What are the expected short- and long
      term effects for the "children of the crisis"? SESPAS report 2014].
AB  - The way a person will develop over the lifespan is largely determined by the
      first few years of life. A substantial share of the inequalities in health and
      socioeconomic status observed in adult life originate during childhood (and even
      while in utero). In this paper, we first review the literature on the impact of
      childhood conditions throughout the life cycle. We next discuss some of the
      social and biological mechanisms behind the transmission of the effects of
      poverty during the prenatal period, childhood, and adulthood. We then analyze
      several international experiences aimed at reducing intergenerational
      transmission of poverty. The article ends with some critical thoughts and policy
      recommendations to avoid the possible long-term effects of the current crisis on
      the health and socioeconomic status of the "children of the crisis" in Spain. 

PMID- 24864003
TI  - Impact of the economic crisis on the health of older persons in Spain: research
      clues based on an analysis of mortality. SESPAS report 2014.
AB  - Older adults are seldom considered in studies on the health impact of economic
      recessions or crises. However, they constitute a population group that is highly
      vulnerable to decreases in investment in health and social services and social
      security. Our aim is to examine the relationship between the economic crisis
      starting in 2008 and the health status of older adults in Spain. More
      specifically, we analyze changes in trends of mortality in relation to the
      crisis, the specific impact of winter on mortality and gender differences in the
      crisis' impact on mortality. Using data from the National Institute of Statistics
      of Spain on people over 60 years of age, the number of monthly deaths by age and
      sex from January 2005 to December 2012 was analyzed. Interrupted time series
      analyses and the "difference in differences" method were used. During the crisis,
      for adults 60 years and older: 1) the observed mortality seems to be decreasing
      at a slower rate than what would have been expected in the absence of the crisis;
      2) there has been an increase in winter mortality; 3) the impact of the crisis
      has been greater for female than for male mortality. These results suggest
      sizable effects of the economic crisis on the mortality of older adults and argue
      for research done using more detailed analyses integrating economic indicators. 

PMID- 24864004
TI  - Investigation of EEG changes during exposure to extremely low-frequency magnetic
      field to conduct brain signals.
AB  - There are evidences that confirm the effect of magnetic fields (MFs) on brain
      signals and some psychological disorders such as headache, migraine and
      depression. The aim of the present study was to investigate changes in EEG power
      spectrum due to localized exposure in different parts of the brain by extremely
      low-frequency magnetic fields (ELF-MFs) to extract some protocols for treatment
      of some psychological disorders. In addition, regular effects were investigated
      by increasing intensity of ELF-MF. Therefore, EEG relative power spectrum was
      evaluated at T4, T3, F3, F4, and Cz points, when all the points were exposed to
      MFs with 45, 17, 10, 5, and 3 Hz frequencies, separately. Intensity of MF was 0,
      100, 240, or 360 MUT in four sessions. Significant changes were observed in
      different EEG bands caused by locally exposing to ELF-MF in different points of
      brain (P < 0.05). Some exposure to MFs decreased alpha band of frontal and
      central areas in closed-eyes state. Based on the findings in this study, some
      protocols can be designed using a combination of various MFs exposures to conduct
      the brain signals that is necessary to evaluate clinically.

PMID- 24864006
TI  - Diborabutatriene: an electron-deficient cumulene.
AB  - The complexation of two equivalents of a cyclic (alkyl)(amino)carbene (CAAC) to
      tetrabromodiborane, followed by reduction with four equivalents of sodium
      naphthalide, led to the formation of the CAAC-stabilized linear diboracumulene
      (CAAC)2B2. The capacity of the CAAC ligand to facilitate B2 ->CAAC donation of pi
      electron density resulted in important differences between this species and a
      previously reported complex featuring a B=B triple bond stabilized by cyclic
      di(amino)carbenes, including a longer B-B bond and shorter B-C bonds. Frontier
      orbital analysis indicated sharing of valence electrons across the entire linear
      C-B-B-C unit in (CAAC)2B2, which is supported by natural population analysis and
      cyclic voltammetry.

PMID- 24864005
TI  - Maximizing exposure therapy: an inhibitory learning approach.
AB  - Exposure therapy is an effective approach for treating anxiety disorders,
      although a substantial number of individuals fail to benefit or experience a
      return of fear after treatment. Research suggests that anxious individuals show
      deficits in the mechanisms believed to underlie exposure therapy, such as
      inhibitory learning. Targeting these processes may help improve the efficacy of
      exposure-based procedures. Although evidence supports an inhibitory learning
      model of extinction, there has been little discussion of how to implement this
      model in clinical practice. The primary aim of this paper is to provide examples
      to clinicians for how to apply this model to optimize exposure therapy with
      anxious clients, in ways that distinguish it from a 'fear habituation' approach
      and 'belief disconfirmation' approach within standard cognitive-behavior therapy.
      Exposure optimization strategies include (1) expectancy violation, (2) deepened
      extinction, (3) occasional reinforced extinction, (4) removal of safety signals,
      (5) variability, (6) retrieval cues, (7) multiple contexts, and (8) affect
      labeling. Case studies illustrate methods of applying these techniques with a
      variety of anxiety disorders, including obsessive-compulsive disorder,
      posttraumatic stress disorder, social phobia, specific phobia, and panic
      disorder.

PMID- 24864007
TI  - Reflections on endovascular treatment for ischaemic stroke. A stroke care plan
      for the Region of Madrid.

PMID- 24864008
TI  - Peptidic ligands to control the three-dimensional self-assembly of quantum rods
      in aqueous media.
AB  - The use of peptidic ligands is validated as a generic chemical platform allowing
      one to finely control the organization in solid phase of semiconductor nanorods
      originally dispersed in an aqueous media. An original method to generate, on a
      macroscopic scale and with the desired geometry, three-dimensional supracrystals
      composed of quantum rods is introduced. In a first step, nanorods are transferred
      in an aqueous phase thanks to the substitution of the original capping layer by
      peptidic ligands. Infrared and nuclear magnetic resonance spectroscopy data prove
      that the exchange is complete; fluorescence spectroscopy demonstrates that the
      emitter optical properties are not significantly altered; electrophoresis and
      dynamic light scattering experiments assess the good colloidal stability of the
      resulting aqueous suspension. In a second step, water evaporation in a
      microstructured environment yields superstructures with a chosen geometry and in
      which nanorods obey a smectic B arrangement, as shown by electron microscopy.
      Incidentally, bulk drying in a capillary tube generates a similar local order, as
      evidenced by small angle X-ray scattering. 

PMID- 24864009
TI  - Laparoscopic and transanal excision of large lower- and mid-rectal deep
      endometriotic nodules: the Rouen technique.
AB  - OBJECTIVE: To report an original technique of combined laparoscopic and transanal
      disc excision of lower- and mid-rectal deep endometriotic nodules. DESIGN: Video
      article introducing a new surgical technique. SETTING: University hospital.
      PATIENT(S): A 30-year-old nullipara with symptomatic deep endometriosis-large
      nodules involving the vagina and the lower rectum over 30 mm. INTERVENTION(S): An
      original technique of combined laparoscopic and transanal approaches, including
      deep rectal shaving using PlasmaJet, followed by transanal full thickness disc
      excision of the shaved area using the Contour Transtar stapler. MAIN OUTCOME
      MEASURE(S): The procedure is based on specific properties of PlasmaJet (the lack
      of lateral thermal spread making the dissection on contact of the rectal wall
      safe, the precise ablative property allowing for in situ ablation of rectal
      endometriosis implants) and those of the Contour Transtar stapler, which was
      originally developed to perform stapled transanal rectal resection of the
      internal rectal prolapse or rectocele. The steps of the Rouen technique and the
      role of the two devices are emphasized. Surgical technique reports in anonymous
      patients are exempted from ethical approval by the Institutional Review Board.
      The patient gave consent to use the video in the article. RESULT(S): The
      patient's functional outcome was uneventful, except for transitory incomplete
      bladder voiding. Since June 2009, we have successfully employed this technique in
      15 patients with low rectal nodules, with only favorable digestive functional
      outcomes. CONCLUSION(S): Our technique is suitable for large nodules involving
      the lower and mid-rectum and avoids low colorectal resection, thus increasing the
      chance of favorable functional digestive outcomes.

PMID- 24864011
TI  - Potential candidate camelid antibodies for the treatment of protein-misfolding
      diseases.
AB  - Protein-misfolding diseases (PMDs), including Alzheimer's disease would
      potentially reach epidemic proportion if effective ways to diagnose and treat
      them were not developed. The quest for effective therapy for PMDs has been
      ongoing for decades and some of the technologies developed so far show great
      promise. We report here the development of antibodies by immunization of camelids
      with prion (PrioV3) and Alzheimer's (PrioAD12, 13 & 120) disease-derived brain
      material. We show that anti-PrP antibody transmigration across the blood-brain
      barrier (BBB) was inhibited with phosphatidylinositol-specific phospholipase C
      (PIPLC). Our camelid anti-prion antibody was also shown to permanently abrogate
      prion replication in a prion-permissive cell line after crossing the artificial
      BBB. Furthermore, anti-Abeta/tau antibodies were able to bind their specific
      immunogens with ELISA and immunohistochemistry. Finally, both PrioV3 and PrioAD12
      were shown to co-localize with Lamp-1, a marker of late endosomal/lysosomal
      compartments. These antibodies could prove to be a valuable tool for the
      neutralization/clearance of PrP(Sc), Abeta and tau proteins in cellular
      compartments of affected neurons and could potentially have wider applicability
      for the treatment of PMDs. 

PMID- 24864012
TI  - Immune complex formation and in situ B-cell clonal expansion in human cerebral
      cavernous malformations.
AB  - Cerebral cavernous malformations (CCMs) represent clusters of dilated vascular
      channels, predisposing to hemorrhagic stroke and seizures. They are associated
      with defective blood brain barrier, hemorrhages of different ages and a robust
      inflammatory cell infiltrate. We report for the first time evidence of co
      localized IgG and complement membrane attack complexes in CCM lesions. CD4(+) and
      CD8(+) T-cells are aggregated with CD20(+) B-cells. And IgG repertoire analyses
      demonstrate in situ B-cell clonal expansion and antigen-driven affinity
      maturation in CCMs. These results suggest an organ-intrinsic adaptive immune
      response in CCMs that should be further characterized as a potential therapeutic
      target. 

PMID- 24864010
TI  - Enrichment of spermatogonial stem cells from long-term cultured human testicular
      cells.
AB  - OBJECTIVE: To evaluate the degree of enrichment of spermatogonial stem cells
      (SSCs) from human testicular cell cultures by ITGA6+, HLA-/ITGA6+, GPR125+, and
      HLA-/GPR125+ magnetic-assisted cell sorting (MACS). DESIGN: Experimental basic
      science study. SETTING: Reproductive biology laboratory. PATIENT(S): Multiple
      samples of cryopreserved human testicular cells from two prostate cancer patients
      with normal spermatogenesis. INTERVENTION(S): Cultured human testicular cells
      subjected to four sorting strategies based on MACS and xenotransplanted to the
      testes of mice to determine the enrichment for SSCs. MAIN OUTCOME MEASURE(S):
      Enrichment for human spermatogonia and SSCs tested by expression analysis of
      spermatogonial markers ITGA6, GPR125, ZBTB16, UCHL1, and ID4 using quantitative
      real-time polymerase chain reaction (qPCR) and by xenotransplantation into the
      testes of mice, respectively. RESULT(S): Compared with the nonsorted cultured
      testicular cells, only the ITGA6+ and HLA-/GPR125+ sorted cells showed enrichment
      for ID4. No difference in expression of ZBTB16 and UCHL1 was observed.
      Xenotransplantation of the sorted cell fractions showed a 7.1-fold enrichment of
      SSCs with ITGA6+. CONCLUSION(S): Magnetic-assisted cell sorting of cultured human
      testicular cells using ITGA6 allows for enrichment of SSCs, which aids in further
      molecular characterization of cultured human SSCs and enhances testicular
      colonization upon transplantation in future clinical settings.

PMID- 24864013
TI  - Identification of alpha-fodrin as an autoantigen in experimental coronavirus
      retinopathy (ECOR).
AB  - The coronavirus, mouse hepatitis virus (MHV), JHM strain induces a biphasic
      disease in BALB/c mice that consists of an acute retinitis followed by
      progression to a chronic retinal degeneration with autoimmune reactivity. Retinal
      degeneration resistant CD-1 mice do not develop either the late phase or
      autoimmune reactivity. A mouse RPE/choroid DNA expression library was screened
      using sera from virus infected BALB/c mice. Two clones were identified, villin-2
      protein and alpha-fodrin protein. alpha-Fodrin protein was used for further
      analysis and western blot reactivity was seen only in sera from virus infected
      BALB/c mice. CD4 T cells were shown to specifically react with MHV antigens and
      with alpha-fodrin protein. These studies clearly identified both antibody and CD4
      T cell reactivities to alpha-fodrin in sera from virus infected, retinal
      degenerative susceptible BALB/c mice. 

PMID- 24864014
TI  - The prehistory of the cytoskeleton concept.
AB  - Here we discuss how the concept and the name of cytoskeleton were generated and
      started to evolve over the last two centuries into what is presently a basic
      topic of modern biology. We also attempt to describe some facets of the emergence
      of cytoskeleton component characterization in which our laboratory was in part
      involved.

PMID- 24864015
TI  - Investigation of gallic acid induced anticancer effect in human breast carcinoma
      MCF-7 cells.
AB  - Gallic acid (GA), a polyhydroxylphenolic compound abundantly distributed in
      plants, fruits, and foods, has been reported to have various biological
      activities including an anticancer effect. In this study, we extensively
      investigated the anticancer effect of GA in human breast carcinoma MCF-7 cells.
      Our study indicated that treatment with GA resulted in inhibition of
      proliferation and induction of apoptosis in MCF-7 cells. Then, the molecular
      mechanism of GA's apoptotic action in MCF-7 cells was further investigated. The
      results revealed that GA induced apoptosis by triggering the extrinsic or
      Fas/FasL pathway as well as the intrinsic or mitochondrial pathway. Furthermore,
      the apoptotic signaling induced by GA was amplified by cross-link between the two
      pathways. Taken together, our findings may be useful for understanding the
      mechanism of action of GA on breast cancer cells and provide new insights into
      the possible application of such compound and its derivatives in breast cancer
      therapy. 

PMID- 24864016
TI  - Dibenzocyclooctadiene lignans from Schisandra chinensis and their inhibitory
      activity on NO production in lipopolysaccharide-activated microglia cells.
AB  - Four dibenzocyclooctadiene lignans, schisanchinins A-D, and 10 known compounds
      were isolated from the EtOAc extract of fruits of Schisandra chinensis (Turcz.)
      Baill. Structures of compounds 1-4 were elucidated using a combination of
      spectroscopic techniques, including MS, UV and IR, NMR ((1)H NMR, (13)C NMR,
      HMQC, HMBC). The stereochemistry of the chiral centers and the biphenyl
      configuration were determined using NOESY, as well as analysis of CD spectra. In
      vitro activity assays showed that 11 of the 14 compounds exhibited inhibitory
      activity on lipopolysaccharide (LPS)-induced NO release in primary murine BV2
      microglia cells. 

PMID- 24864017
TI  - Two types of alcohol dehydrogenase from Perilla can form citral and
      perillaldehyde.
AB  - Studies on the biosynthesis of oil compounds in Perilla will help in
      understanding regulatory systems of secondary metabolites and in elucidating
      reaction mechanisms for natural product synthesis. In this study, two types of
      alcohol dehydrogenases, an aldo-keto reductase (AKR) and a geraniol dehydrogenase
      (GeDH), which are thought to participate in the biosynthesis of perilla essential
      oil components, such as citral and perillaldehyde, were isolated from three pure
      lines of perilla. These enzymes shared high amino acid sequence identity within
      the genus Perilla, and were expressed regardless of oil type. The overall
      reaction from geranyl diphosphate to citral was performed in vitro using geraniol
      synthase and GeDH to form a large proportion of citral and relatively little
      geraniol as reaction products. The biosynthetic pathway from geranyl diphosphate
      to citral, the main compound of citral-type perilla essential oil, was
      established in this study. 

PMID- 24864018
TI  - Second-trimester prediction of delivery of a small-for-gestational-age neonate:
      integrating sequential Doppler information, fetal biometry, and maternal
      characteristics.
AB  - OBJECTIVE: The aim of this study was to investigate the predictive accuracy of
      second-trimester ultrasound parameters, maternal characteristics, and sequential
      Doppler changes between first and second trimesters for the prediction of small
      for-gestational-age (SGA) infants (birth weight < 10th percentile). METHODS: We
      conducted a prospective study of singleton pregnancies enrolled in the first
      trimester with subsequent second-trimester follow-up. Maternal characteristics,
      uterine artery (UtA) pulsatility index (PI), fetal biometry, and umbilical artery
      (UA)-PI were ascertained. UtA and UA-PI change from first to second trimester was
      calculated (DeltaUtA-PI and DeltaUA-PI). These parameters were tested for their
      ability to predict delivery of an SGA infant. RESULTS: Among 1982 women, 172
      delivered an SGA neonate. African-American ethnicity, nulliparity, tobacco use,
      and low abdominal circumference (AC) z-score were independent predictors of SGA.
      No difference was found in the magnitude of DeltaUtA-PI and DeltaUA-PI between
      SGA and no-SGA. Receiver-operating characteristics curve analysis yielded an area
      under the curve of 0.700 for AC z-score. The combination of low AC and bilateral
      notching had high specificity (99%) but low sensitivity (7%) for SGA prediction.
      CONCLUSIONS: A small second-trimester fetal AC is a specific marker for SGA when
      found with bilateral UtA notching. Only a small proportion is predicted by the
      factors studied, suggesting a small contributory role or later evolution of SGA.

PMID- 24864020
TI  - COL4A1 mutations should not be a contraindication for epilepsy surgery.
AB  - PURPOSE: We describe the first case in the literature of complication-free
      epilepsy surgery in a paediatric patient with collagen type IV alpha 1 (COL4A1)
      mutation. METHODS: This is a case report. RESULTS: COL4A1 mutations disrupt the
      integrity of vascular basement membranes, so predisposing to a broad spectrum of
      disorders including periventricular leucomalacia, haemorrhagic stroke, aneurysm
      formation, epilepsy and developmental delay. Intracranial haemorrhage is reported
      and may be recurrent or associated with trauma and anticoagulant therapy.
      Children have an increased risk of stroke with general anaesthesia. A 6-year-old
      girl, COL4A1 mutation positive, had drug-resistant epilepsy, cerebral palsy and
      developmental delay. Following presurgical evaluation, she was a candidate for
      corpus callosotomy. Previous general anaesthesia had been uncomplicated.
      Preoperative full blood count and coagulation studies were normal.
      Perioperatively, normotension was maintained, and anticoagulation was avoided. A
      complete corpus callosotomy was performed with no intracranial haemorrhage or
      other perioperative complications. CONCLUSION: Although there is an increased
      risk of intracranial haemorrhages in COL4A1 patients, this is not clearly
      quantifiable. There are minimal data in the literature on the subject. COL4A1
      mutations should not be a contraindication for presurgical evaluation. Each
      patient should be individually evaluated and assessed, risks and benefits were
      carefully weighed, and informed decisions were reached after thorough discussions
      with patients and families.

PMID- 24864019
TI  - Isolated intracranial Rosai-Dorfman disease in a child, a case report and review
      of the literature.
AB  - BACKGROUND: Rosai-Dorfman disease (RDD), otherwise known as sinus histiocytosis
      with massive lymphadenopathy (SHML), usually affects young adults and commonly
      presents with massive painless cervical lymphadenopathy. Extranodal disease is
      present in a third of patients, and it is recognised that this can involve the
      central nervous system. Intracranial RDD is rare in adults and fewer than 10
      paediatric cases have been reported. CASE: A 10-year-old boy with isolated
      intracranial RDD presents with a painless forehead mass. The management is
      discussed and the literature reviewed. CONCLUSION: This case of isolated
      intracranial RDD highlights the importance of considering RDD in the differential
      of paediatric intracranial mass lesions and outlines the diagnostic and treatment
      challenges faced when managing this rare condition.

PMID- 24864021
TI  - Multilevel thoracic hemangioma with spinal cord compression in a pediatric
      patient: case report and review of the literature.
AB  - PURPOSE: Vertebral hemangiomas are common benign vascular tumors of the spine. It
      is very rare for these lesions to symptomatically compress neural elements. If
      spinal cord compression does occur, it usually involves only a single level.
      Multilevel vertebral hemangiomas causing symptomatic spinal cord compression have
      never been reported in the pediatric population to the best of our knowledge.
      METHODS: We report the case of a 15-year-old boy presenting with progressive
      paraparesis due to thoracic spinal cord compression from a multilevel thoracic
      hemangioma (T5-T10) with epidural extension. RESULTS: Because of his progressive
      neurological deficit, he was initially treated with urgent multilevel
      decompressive laminectomies from T4 to T11. This was to be followed by
      radiotherapy for residual tumor, but the patient was unfortunately lost to follow
      up. He re-presented 3 years later with recurrent paraparesis and progressive
      disease. This was treated with urgent radiotherapy with good response. As of 6
      months follow-up, he has made an excellent neurological recovery. CONCLUSIONS: In
      this report, we present the first case of a child with multilevel vertebral
      hemangiomas causing symptomatic spinal cord compression and review the literature
      to detail the pathophysiology, management, and treatment of other cases of spinal
      cord compression by vertebral hemangiomas.

PMID- 24864022
TI  - Management of positional plagiocephaly--helmet or no helmet?

PMID- 24864024
TI  - Translating bioinorganic chemistry.

PMID- 24864027
TI  - Threshold levels of 25-hydroxyvitamin D and parathyroid hormone for impaired bone
      health in children with congenital ichthyosis and type IV and V skin.
AB  - BACKGROUND: Patients with congenital ichthyosis, especially those with darker
      skin types, are at increased risk of developing vitamin D deficiency and rickets.
      The relationships between 25-hydroxyvitamin D [25(OH)D], parathyroid hormone
      (PTH) and bone health have not been studied previously, in ichthyosis.
      OBJECTIVES: To determine the threshold levels of 25(OH)D and PTH for impaired
      bone health in children with congenital ichthyosis. METHODS: In this cross
      sectional study, 119 children with ichthyosis and 168 controls were recruited.
      Serum 25(OH)D, PTH, calcium, phosphate and alkaline phosphatase (ALP) were
      measured. Radiological screening for rickets was carried out only in children
      with ichthyosis. RESULTS: Forty-seven children with ichthyosis had either
      clinical or radiological evidence of rickets. The correlation between serum
      25(OH)D and PTH showed that a serum level of 25(OH)D 8 ng mL(-1) was associated
      with a significant increase in PTH. The correlation between PTH and ALP showed
      that a serum PTH level of 75 pg mL(-1) was associated with a significant increase
      in ALP levels. Of the different clinical phenotypes of ichthyosis, both autosomal
      recessive congenital ichthyosis (ARCI) and epidermolytic ichthyosis (EI) were
      found to have significantly increased PTH, ALP and radiological rickets scores
      compared with common ichthyosis. CONCLUSIONS: Serum levels of 25(OH)D <= 8 ng mL(
      1) and PTH >= 75 pg mL(-1) significantly increases the risk for development of
      rickets [odds ratio (OR) 2.8; 95% confidence interval (CI) 1.05-7.40; P = 0.04]
      in ichthyosis. Among the different types, patients with ARCI (OR 4.83; 95% CI
      1.74-13.45; P < 0.01) and EI (OR 5.71; 95% CI 1.74-18.79; P < 0.01) are at an
      increased risk of developing rickets.

PMID- 24864028
TI  - Impulsive action and impulsive choice across substance and behavioral addictions:
      cause or consequence?
AB  - Substance use disorders are prevalent and debilitating. Certain behavioral
      syndromes ('behavioral addictions') characterized by repetitive habits, such as
      gambling disorder, stealing, shopping, and compulsive internet use, may share
      clinical, co-morbid, and neurobiological parallels with substance addictions.
      This review considers overlap between substance and behavioral addictions with a
      particular focus on impulsive action (inability to inhibit motor responses), and
      impulsive choice (preference for immediate smaller rewards to the detriment of
      long-term outcomes). We find that acute consumption of drugs with abuse potential
      is capable of modulating impulsive choice and action, although magnitude and
      direction of effect appear contingent on baseline function. Many lines of
      evidence, including findings from meta-analyses, show an association between
      chronic drug use and elevated impulsive choice and action. In some instances,
      elevated impulsive choice and action have been found to predate the development
      of substance use disorders, perhaps signifying their candidacy as objective
      vulnerability markers. Research in behavioral addictions is preliminary, and has
      mostly focused on impulsive action, finding this to be elevated versus controls,
      similar to that seen in chronic substance use disorders. Only a handful of
      imaging studies has explored the neural correlates of impulsive action and choice
      across these disorders. Key areas for future research are highlighted along with
      potential implications in terms of neurobiological models and treatment. In
      particular, future work should further explore whether the cognitive deficits
      identified are state or trait in nature: i.e. are evident before addiction
      perhaps signaling risk; or are a consequence of repetitive engagement in habitual
      behavior; and effects of novel agents known to modulate these cognitive abilities
      on various addictive disorders. 

PMID- 24864029
TI  - Two-year experience with mycophenolate mofetil in patients with scleroderma lung
      disease: a case series.
AB  - To assess the effect of mycophenolate mofetil (MMF) on pulmonary functions in
      patients with systemic sclerosis-associated lung disease (SSc-ILD) who
      experienced an inadequate response to first line cyclophosphamide (CYC) therapy.
      Twelve consecutive SSc-ILD patients who received MMF due to inadequate response
      to CYC as a first line agent, were retrospectively reviewed. Over the course of 2
      years, pulmonary function tests (PFT) and high-resolution computed tomography
      (HRCT) scans were performed. Following initial baseline tests, PFTs were
      continued at a frequency of every 6 months and HRCT scans were performed every 12
      months. After MMF treatment, values of forced vital capacity (FVC) and diffusing
      capacity for carbon monoxide (DLCO) improved in three (25%) and two (16.6%)
      patients, respectively. It is also noted that the evaluation of serial HCRT scans
      showed no change in 54.5% of patients. Our case series suggested that PFT and
      imaging scores seemed to be stabilized by MMF in SSc-ILD patients who were
      inadequate responders to CYC.

PMID- 24864030
TI  - [Developmental trauma--differences between the course of inpatient treatment in
      adolescent patients with or without trauma history].
AB  - SUMMARY OBJECTIVE: Aim of the study was to examine differences between the course
      of inpatient treatment in adolescents with different extents of trauma history.
      METHODS: Using multilevel analysis, we investigated the differences between the
      course of inpatient treatment in adolescents without trauma history, with
      emotional trauma and complex trauma. RESULTS: Regarding the GSI of the SCL-90-R,
      patients with trauma history showed significantly more symptom reduction than
      patients without trauma history. In terms of interpersonal problems (IIP)
      especially adolescents with emotional trauma seemed to benefit. CONCLUSIONS:
      Especially patients with trauma history benefited from the examined inpatient
      treatment concept. However, our results also show that the complex traumatized
      patients required longer treatment duration since they benefited particularly in
      the last phase of inpatient treatment.

PMID- 24864031
TI  - [Outpatient psychosocial counseling--results of a user-based cross-sectional
      study about patient reported needs and its consideration].
AB  - BACKGROUND: This article presents results of a user-based cross-sectional study
      about patient reported needs and its consideration in the course of outpatient
      psychosocial counseling. In addition, patient satisfaction with consultations was
      evaluated. METHOD: A sample of 1 930 cancer patients or family caregivers who
      consulted one of 26 psychosocial counseling units funded by German Cancer Aid
      completed a questionnaire sent by mail. RESULTS: Younger and female patients/care
      givers, and those with ovarian, pancreatic and cns tumours were more likely to
      seek counseling. Overall, patient reported needs were met to a high degree. The
      majority of the participants was very satisfied with different aspects of
      counseling. However, 16% of participants reported unmet needs and had suggestions
      for improvements primarily with regard to the counselor (4% of the participants)
      and time management (2% of the participants). In addition, 10% of the
      participants suggested optimizing the counseling location and setting as well as
      the accessibility, time scheduling and the work approach of the staff (1-5%).
      DISCUSSION: Our findings represent a part of the core evaluation of psychosocial
      counseling for cancer patients. Overall, it can be highlighted that cancer
      patients are very satisfied with outpatient psychosocial counseling offers.
      However, few critical aspects could be identified from the clients' perspective.
      Our results are discussed in the context of methodological aspects of the study.

PMID- 24864032
TI  - [Screening and brief intervention in primary care: barriers against an early
      intervention for patients with alcohol misuse].
AB  - STUDY GOAL: The effectiveness of screening and brief intervention (SBI) to reduce
      alcohol consumption has been shown by several studies in primary care. In spite
      of many attempts to establish SBI in routine care only a few patients are treated
      accordingly. Therefore in the study the General Practitioners' (GPs) assessment
      of barriers was investigated and tested for social desirability bias in order to
      determine barriers which are underestimated by GPs. METHOD: The questionnaire was
      sent to 700 GPs in Saxony-Anhalt. RESULTS: 178 questionnaires were analysed.
      Strong agreement could be found for barriers such as insufficient reimbursement
      and insufficient adherence of patients. GPs with low social desirability bias
      felt more awkward about asking patients about alcohol consumption and assessed
      SBI as less relevant for general practice. CONCLUSION: Primary care prevention of
      dependency should be advanced on the basis of a more elaborate knowledge of
      motivational effects of relevant barriers.

PMID- 24864034
TI  - Controlled nanodimensional supramolecular self-assembly of tetra-alkylated
      naphthalene diimide derivatives.
AB  - Construction of thermodynamically stable nanostructures on the nano- to
      millimeter scales through noncovalent bonding plays an important role in material
      science. The self-assembly of tetra-alkylamino core-substituted naphthalene
      diimides (cNDIs) with variable alkyl chains (C8H17, C12H25, and C16H33) added on
      to the core leads to the formation of a variety of controlled morphologies and
      well-defined nanostructures. Such structures include nanorods, vesicular, belts,
      twisted ribbons, and donutlike morphologies (formed in CHCl3/MeOH and
      CHCl3/hexane mixtures) generated through solvophobic control. UV/Vis absorption
      and fluorescence spectroscopy demonstrate molecular aggregation in solution.
      Furthermore, SEM was employed to visualize the supramolecular self-assembled
      nanostructures. The growth of these structures is mainly due to packing of
      hydrophobic alkyl chains and pi-pi stacking of the cNDI core. The present study
      paves the way to rational and controlled designs of nanostructures made of
      optically active dyes (naphthalene diimide); this may open a new avenue towards
      tuning nanodimensional morphology.

PMID- 24864023
TI  - Primary cilia in pancreatic development and disease.
AB  - Primary cilia and their anchoring basal bodies are important regulators of a
      growing list of signaling pathways. Consequently, dysfunction in proteins
      associated with these structures results in perturbation of the development and
      function of a spectrum of tissue and cell types. Here, we review the role of
      cilia in mediating the development and function of the pancreas. We focus on
      ciliary regulation of major pathways involved in pancreatic development,
      including Shh, Wnt, TGF-beta, Notch, and fibroblast growth factor. We also
      discuss pancreatic phenotypes associated with ciliary dysfunction, including
      pancreatic cysts and defects in glucose homeostasis, and explore the potential
      role of cilia in such defects.

PMID- 24864033
TI  - A survey of five broad-host-range plasmids in gram-negative bacilli isolated from
      patients.
AB  - OBJECTIVES: To learn the prevalence of the primary classical broad-host-range
      (BHR) IncA/C, IncN, IncP, IncQ, and IncW plasmids in dominant gram-negative
      bacilli from inpatients in a teaching hospital in southern China. METHODS: A
      multiplex polymerase chain reaction based on the replicons of BHR IncA/C, IncN,
      IncP, IncQ, and IncW plasmids was developed and used to determine these BHR
      plasmids. The difference in prevalence rates among the different species from
      three specimens was evaluated by a binary logistic regression model and the
      differences between multidrug-resistant organisms (MDRO) and non-MDRO were
      assessed using a chi-square test. RESULTS: The average positive detection
      percentages of the replicons were 4.3%, 3.7%, 3.0%, 2.6%, and 1.9%, respectively,
      for IncN, IncP, IncQ, IncW, and IncA/C in descending order. The distribution of
      all five BHR plasmids did not differ significantly between specimens collected
      from wounds and urine, although both were significantly higher than those of
      sputum. The prevalence rates of all five BHR plasmids in MDROs were significantly
      higher than those in non-MDRO for Enterobacteriaceae; however, no significant
      difference was seen in non-fermenting gram-negative bacilli (NFGNB). CONCLUSIONS:
      BHR IncA/C, IncN, IncP, IncQ, and IncW plasmids, which occur more often in
      bacilli from wound and urine specimens than those of sputum, are widespread in
      Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Enterobacter cloacae,
      Pseudomonas aeruginosa, and Acinetobacter baumannii strains isolated from
      inpatients. The prevalence rates in MDRO are higher than those in non-MDRO for
      Enterobacteriaceae but not significantly different for NFGNB.

PMID- 24864035
TI  - The cold-adapted gamma-glutamyl-cysteine ligase from the psychrophile
      Pseudoalteromonas haloplanktis.
AB  - A recombinant gamma-glutamyl-cysteine ligase from the psychrophile
      Pseudoalteromonas haloplanktis (rPhGshA II) was produced and characterised. This
      enzyme catalyses the first step of glutathione biosynthesis by forming gamma
      glutamyl-cysteine from glutamate and cysteine in an ATP-dependent reaction. The
      other ATP-dependent enzyme, glutathione synthetase (rPhGshB), involved in the
      second step of the biosynthesis, was already characterised. rPhGshA II is a
      monomer of 58 kDa and its activity was characterised through a direct
      radioisotopic method, measuring the rate of ATP hydrolysis. The enzyme was active
      even at cold temperatures in a moderately alkaline buffer containing a high
      concentration of Mg(++); 2-aminobutyrate could replace cysteine, although a lower
      activity was detected. The reaction rate of rPhGshA II at 15  degrees C was
      higher than that reported for rPhGshB, thus suggesting that formation of gamma
      glutamyl-cysteine was not the rate limiting step of glutathione biosynthesis in
      P. haloplanktis. rPhGshA II had different affinities for its substrates, as
      evaluated on the basis of the KM values for ATP (0.093 mM), glutamate (2.8 mM)
      and cysteine (0.050 mM). Reduced glutathione acted as an inhibitor of rPhGshA II,
      probably through the binding to an enzyme pocket different from the active site.
      Also the oxidised form of glutathione inhibited the enzyme with a more complex
      inhibition profile, due to the complete mono-glutathionylation of rPhGshA II on
      Cys 386, as proved by mass spectrometry data. When compared to rPhGshB, rPhGshA
      II possessed more typical features of a psychrophilic enzyme, as it was endowed
      with lower thermodependence and higher heat sensitivity. In conclusion, this work
      extends the knowledge on glutathione biosynthesis in the first cold-adapted
      source; however, another possible redundant gamma-glutamyl-cysteine ligase
      (PhGshA I), not yet characterised, could participate in the biosynthesis of this
      cellular thiol in P. haloplanktis. 

PMID- 24864036
TI  - A novel homozygous mutation in FGFR3 causes tall stature, severe lateral tibial
      deviation, scoliosis, hearing impairment, camptodactyly, and arachnodactyly.
AB  - Most reported mutations in the FGFR3 gene are dominant activating mutations that
      cause a variety of short-limbed bone dysplasias including achondroplasia and
      syndromic craniosynostosis. We report the phenotype and underlying molecular
      abnormality in two brothers, born to first cousin parents. The clinical picture
      is characterized by tall stature and severe skeletal abnormalities leading to
      inability to walk, with camptodactyly, arachnodactyly, and scoliosis. Whole exome
      sequencing revealed a homozygous novel missense mutation in the FGFR3 gene in
      exon 12 (NM_000142.4:c.1637C>A: p.(Thr546Lys)). The variant is found in the
      kinase domain of the protein and is predicted to be pathogenic. It is located
      near a known hotspot for hypochondroplasia. This is the first report of a
      homozygous loss-of-function mutation in FGFR3 in human that results in a skeletal
      overgrowth syndrome. 

PMID- 24864037
TI  - Associating liver partition and portal vein ligation for staged hepatectomy
      (ALPPS): an analysis of tumor activity.

PMID- 24864038
TI  - Design and synthesis of novel and highly-active pan-histone deacetylase (pan
      HDAC) inhibitors.
AB  - Histone deacetylase (HDAC) inhibitions are known to elicit anticancer effects. We
      designed and synthesized several HDAC inhibitors. Among these compounds, compound
      40 exhibited a more than 10-fold stronger inhibitory activity compared with that
      of suberoylanilide hydroxamic acid (SAHA) against each human HDAC isozyme in
      vitro (IC50 values of 40: HDAC1, 0.0038MUM; HDAC2, 0.0082MUM; HDAC3, 0.015MUM;
      HDAC8, 0.0060MUM; HDAC4, 0.058MUM; HDAC9, 0.0052MUM; HDAC6, 0.058MUM). The dose
      of the administered HDAC inhibitors that contain hydroxamic acid as the zinc
      binding group may be reduced by 40. Because the carbostyril subunit is a time
      tested structural component of drugs and biologically active compounds, 40 most
      likely exhibits good absorption, distribution, metabolism, excretion, and
      toxicity (ADMET). Thus, compound 40 is expected to be a promising therapeutic
      agent or chemical tool for the investigation of life process. 

PMID- 24864039
TI  - Macrocyclic diterpenes resensitizing multidrug resistant phenotypes.
AB  - Herein, collateral sensitivity effect was exploited as a strategy to select
      effective compounds to overcome multidrug resistance in cancer. Thus, eleven
      macrocyclic diterpenes, namely jolkinol D (1), isolated from Euphorbia
      piscatoria, and its derivatives (2-11) were evaluated for their activity on three
      different Human cancer entities: gastric (EPG85-257), pancreatic (EPP85-181) and
      colon (HT-29) each with a variant selected for resistance to mitoxantrone (EPG85
      257RN; EPP85-181RN; HT-29RN) and one to daunorubicin (EPG85-257RD; EPP85-181RD;
      HT-29RD). Jolkinol D (1) and most of its derivatives (2-11) exhibited significant
      collateral sensitivity effect towards the cell lines EPG85-257RN (associated with
      P-glycoprotein overexpression) and HT-29RD (altered topoisomerase II expression).
      The benzoyl derivative, jolkinoate L (8) demonstrated ability to target different
      cellular contexts with concomitant high antiproliferative activity. These
      compounds were previously assessed as P-glycoprotein modulators, at non-cytotoxic
      doses, on MDR1-mouse lymphoma cells. A regression analysis between the
      antiproliferative activity presented herein and the previously assessed P
      glycoprotein modulatory effect showed a strong relation between the compounds
      that presented both high P-glycoprotein modulation and cytotoxicity. 

PMID- 24864041
TI  - Synthesis and evaluation of (E)-2-(acrylamido)cyclohex-1-enecarboxylic acid
      derivatives as HCA1, HCA2, and HCA3 receptor agonists.
AB  - 2-(3-(Naphthalen-2-yl)propanamido)cyclohex-1-enecarboxylic acid and its 6
      hydroxynaphthalen-2-yl analogue are well-known hydroxyl-carboxylic acid (HCA)
      receptor HCA2 agonists. A series of novel aryl derivatives of 2-amidocyclohex-1
      ene carboxylic acid that contained rigidity elements, such as an E-double bond,
      triple bond, and trans or cis-substituted cyclopropane rings, instead of the
      saturated ethane linker in the amide part of the molecules were designed and
      synthesized, and the derivatives' potency for the activation of HCA1, HCA2, and
      HCA3 receptors by 3'-5'-cyclic adenosine monophosphate (cAMP) assay were
      evaluated. The SAR studies revealed that the rigidifying of appropriate molecules
      enabled modulation of the potency and selectivity of the HCA2 receptor
      activation. 

PMID- 24864042
TI  - Therapeutic Apheresis Academy 2013: beyond borders.

PMID- 24864040
TI  - The unique chemistry of benzoxaboroles: current and emerging applications in
      biotechnology and therapeutic treatments.
AB  - Benzoxaboroles have garnered much attention in recent years due to their diverse
      applications in bio-sensing technology, material science, and therapeutic
      intervention. Part of the reason arises from the benzoxaboroles' unique chemical
      properties, especially in comparison to their acyclic boronic acid counterparts.
      Furthermore, the low bio-toxicity combined with the high target specificity
      associated with benzoxaboroles make them very attractive as therapeutic agents.
      Herein, we provide an updated summary on the current knowledge of the fundamental
      chemical reactivity of benzoxaboroles, followed by highlighting their major
      applications reported to date. 

PMID- 24864043
TI  - Evolutionary history of trihelix family and their functional diversification.
AB  - In this study, we carried out an evolutionary, transcriptional, and functional
      analyses of the trihelix transcription factor family. A total of 319 trihelix
      members, identified from 11 land plant species, were classified into five clades.
      The results of phylogeny indicate the binding domains of GT1 and GT2 diverged
      early in the existence of land plants. Genomic localization revealed that the
      trihelix family members were highly conserved among cereal species, even though
      some homeologs generated during the tetraploidy of maize were lost. Three
      dimensional structural analyses and an examination of subcellular localization of
      this family supported the involvement of all five clades in transcriptional
      regulation. Furthermore, the family members from all clades in sorghum and rice
      showed a broad and dynamic expression pattern in response to abiotic stresses,
      indicating regulatory subfunctionalization of their original functions. This
      finding is further supported by the phenotypes of enhanced tolerance to cold,
      salt, and drought in transgenic plants overexpressing Sb06g023980 and
      Sb06g024110. In contrast, few Arobidopsis genes showed inducible expression under
      abiotic stress conditions, which may indicate a functional shift. Finally, our co
      expression analysis points to the involvement of this family in various metabolic
      processes, implying their further functional divergence. 

PMID- 24864044
TI  - Genetic Drift Linked to Heterogeneous Landscape and Ecological Specialization
      Drives Diversification in the Alpine Endemic Columbine Aquilegia thalictrifolia.
AB  - The European Alpine system is an extensive mountain range, whose heterogeneous
      landscape together with Quaternary climatic oscillations significantly affected
      organismal diversity and distribution in Europe. The model genus Aquilegia
      represents a textbook example of a rapid and recent radiation through the
      Northern hemisphere, with the majority of the European taxa occuring in the
      Alpine system. However, the processes governing genetic differentiation of the
      genus in this complex geographic area are still widely unexplored. In this work,
      we used 9 microsatellite loci to study the genetic structure and diversity of 11
      populations of Aquilegia thalictrifolia Schott & Kotschy, an alpine taxon
      characterized by a marked ecological specificity. We found that, despite the
      endemic and fragmented distribution, A. thalictrifolia has overall high levels of
      heterozygosity, which is consistent to the substantial inbreeding depression that
      characterizes the genus. Strong spatial genetic structuring of populations
      suggests a historical prevalence of genetic drift over gene flow, with natural
      barriers and ecological niche hindering migration. An analytical comparison of
      fixation and population differentiation indexes allowed us to infer hypotheses of
      the postglacial history and more recent demographic events that have influenced
      the genetics of the species. Overall, our results indicate allopatry as a major
      force of differentiation in the European scenario, likely to underlie the
      development of taxonomic boundaries in a broader geographic context. This adds to
      previous notions on the primary evolutionary forces shaping the Aquilegia
      radiation in Europe.

PMID- 24864045
TI  - Relationship between heart rate and mortality and morbidity in the irbesartan
      patients with heart failure and preserved systolic function trial (I-Preserve).
AB  - BACKGROUND: Higher heart rate is associated with poorer outcomes in patients with
      heart failure and reduced ejection fraction (HF-REF). Less is known about the
      association between heart rate and outcomes in patients with heart failure and
      preserved ejection fraction (HF-PEF). Therefore, we examined the relationship
      between heart rate and outcomes in the irbesartan in patients with heart failure
      and preserved systolic function trial (I-Preserve) in patients with an ejection
      fraction >45% aged >60 years. METHODS AND RESULTS: Heart rate was analysed as
      both a categorical (tertiles) and continuous variable. Patients in sinus rhythm
      (n = 3271) and atrial fibrillation (n = 696) were analysed separately. The
      outcomes examined were the primary endpoint of the trial (all-cause death or
      cardiovascular hospitalization), the composite of cardiovascular death or heart
      failure hospitalization (and its components) and all-cause death alone. Higher
      heart rate was associated with a significantly higher risk of all outcomes
      studied for patients in sinus rhythm, even after adjustment for other prognostic
      variables, including N-terminal pro-B-type natriuretic peptide. Each standard
      deviation (12.4 bpm) increase in heart rate was associated with an increase in
      risk of 13% for cardiovascular death or heart failure hospitalization (P =
      0.002). No relationship between heart rate and outcomes was observed for patients
      in atrial fibrillation. Beta-blocker treatment did not reduce the heart rate-risk
      relationship. CONCLUSIONS: In patients with heart failure and preserved ejection
      fraction, heart rate is in sinus rhythm an independent predictor of adverse
      clinical outcomes and might be a therapeutic target in this syndrome. Clinical
      Trial Registration - URL http://www.clinicaltrials.gov. Unique identifier: NCT
      0095238.

PMID- 24864047
TI  - Transient MEK inhibitor-associated retinopathy in metastatic melanoma.
AB  - BACKGROUND: Melanoma is one of the most aggressive skin cancers. Recently,
      selective MEK inhibitors have shown efficacy in patients with advanced BRAF- and
      NRAS-mutant melanoma. Soon after the initiation of clinical oncology trials with
      MEK inhibitors, it was observed that some participants developed an eye condition
      resembling central serous chorioretinopathy. The present article addresses the
      clinical features and management of these MEK inhibitor-associated retinal
      syndromes. PATIENTS AND METHODS: Thirty-two patients with advanced cutaneous
      melanoma were treated with the selective MEK inhibitor binimetinib (MEK162) in
      three different Phase 1b or 2 clinical trials. Twenty patients on binimetinib
      monotherapy and 12 on binimetinib plus RAF inhibitor [pan-kinase RAF inhibitor
      RAF265 (n = 7) or selective BRAF inhibitor encorafenib (LGX818) (n = 5)]
      combination therapy underwent ophthalmological examinations at regular intervals,
      including determination of best corrected visual acuity, perimetry, colour vision
      testing, dilated fundus examination, and multimodal imaging. RESULTS: Grade 1-2
      bilateral retinopathies with multiple lesions were observed in 13 of 20 patients
      on binimetinib monotherapy, 4 of 7 patients on binimetinib plus RAF265
      combination therapy, and 2 of 5 patients on binimetinib plus encorafenib
      combination therapy. In this study population, the rate ranged from 40% to 65%.
      Retinopathy events appeared during the first 4 weeks, and in some cases, during
      the first few days of treatment. Patients reported mild and only short-lived
      visual symptoms. Optical coherence tomography revealed neuroretinal elevations.
      Central retinal thickness and volume showed dose-dependent increases after the
      start of treatment, followed by a marked decrease despite continued treatment,
      which was associated with symptom resolution. No vascular abnormalities were
      found with fluorescein and indocyanine green angiography. CONCLUSIONS: Treatment
      with the selective MEK inhibitor binimetinib as a single agent or in combination
      with RAF inhibitors induced transient retinopathy with multiple bilateral lesions
      in some patients. Binimetinib-induced retinopathy was usually mild, self
      limiting, and tolerable as visual function was not seriously impaired.

PMID- 24864046
TI  - Effects of varying tissue sizes on the efficiency of baboon ovarian tissue
      vitrification.
AB  - OBJECTIVE: The aim of this study was to detect the effects of varying tissue
      sizes on the efficiency of baboon ovarian tissue vitrification. STUDY DESIGN: The
      percentages of morphologically normal primordial follicles and the follicles
      expressing bax protein in ovarian tissues after vitrification-warming were
      measured. Besides, the 17-beta estradiol levels in the culture supernatants were
      measured. RESULTS: The percentages of morphologically normal primordial follicles
      in vitrified-warmed ovarian tissues slicing in 0.5-1.5mm in length and wide, and
      1.0mm in thickness were significantly higher than those slicing in 2.0mm in
      length and wide, and 1.0mm in thickness. Moreover, the follicles expressing bax
      protein in vitrified-warmed ovarian tissues slicing in 0.5-1.5mm in length and
      wide, and 1.0mm in thickness were significantly lower than those slicing in 2.0mm
      in length and wide, and 1.0mm in thickness. The 17-beta estradiol levels in the
      culture supernatants slicing in 1.0-1.5mm in length and wide, and 1.0mm in
      thickness were significantly higher than those slicing in 0.5mm or 2.0mm in
      length and wide, and 1.0mm in thickness. CONCLUSIONS: Cortex piece slicing in 1.0
      1.5mm in length and wide, and 1.0mm in thickness is suitable for baboon ovarian
      vitrification.

PMID- 24864049
TI  - Increase in physical activities in kindergarten children with cerebral palsy by
      employing MaKey-MaKey-based task systems.
AB  - In this study, we employed Flash- and Scratch-based multimedia by using a MaKey
      MaKey-based task system to increase the motivation level of children with
      cerebral palsy to perform physical activities. MaKey MaKey is a circuit board
      that converts physical touch to a digital signal, which is interpreted by a
      computer as a keyboard message. In this study, we used conductive materials to
      control this interaction. This study followed single-case design using ABAB
      models in which A indicated the baseline and B indicated the intervention. The
      experiment period comprised 1 month and a half. The experimental results
      demonstrated that in the case of two kindergarten children with cerebral palsy,
      their scores were considerably increased during the intervention phrases. The
      developmental applications of the results are also discussed.

PMID- 24864050
TI  - Health information exchange in general practice care for people with intellectual
      disabilities--a qualitative review of the literature.
AB  - Many barriers to the provision of general practice (GP) care for people with
      intellectual disabilities (ID) relate to problems in exchanging health
      information. Deficits in the exchange of health information may have an adverse
      impact on healthcare access and health outcomes in individuals with ID. The aim
      of this paper is to report how health information exchange (HIE) in GP care for
      people with ID is being described in the ID healthcare literature. Thematic
      analysis of 19 included articles resulted in six major themes: (1) communication
      skills; (2) organisational factors; (3) record keeping and sharing; (4) health
      literacy and self-advocacy; (5) carers and health professionals' knowledge; and
      (6) third parties. The results indicate that HIE takes place in a chain of events
      happening before, during, and after a medical consultation, depending on specific
      contextual care factors. The included papers lack a broad focus on the entire HIE
      process, and causes and effects of gaps in health information are described only
      marginally or on a very general level. However, a study of the HIE process in its
      entirety is imperative in order to identify weak links and gaps in information
      pathways. The themes presented here provide a starting point for an in-depth
      study on the HIE process in GP care for individuals with ID that may facilitate
      future research on health interventions in this setting. 

PMID- 24864048
TI  - Prevalence of extended treatment in pulmonary tuberculosis patients receiving
      first-line therapy and its association with recurrent tuberculosis in Beijing,
      China.
AB  - BACKGROUND: In China, it is known that extended treatment is given to patients
      with pulmonary TB after they have successfully completed 6 months of first-line
      treatment. This practice is not officially reported to the National Tuberculosis
      Control Programme, so there are no data on its prevalence, its possible benefits
      in terms of preventing recurrent disease or the costs. This study aimed to
      provide information, from a single TB dispensary in Beijing, China, on the
      prevalence of extended anti-TB treatment and its relationship with recurrent TB.
      METHODS: Retrospective cohort study using the electronic national TB information
      system and dispensary medical records. RESULTS: Of 935 patients with pulmonary TB
      who completed 6-7 months of first-line drug treatment, 399 (43%) were given
      extended treatment. This was more common in patients with smear-positive disease,
      and those with lung cavities and more extensive radiographic lobar involvement at
      the time of diagnosis. Over 3-4 years' follow-up, recurrent disease was not
      significantly different in patients who received extended treatment (2.8%,
      11/399) as compared to those who received the standard 6-month treatment (3.7%,
      20/534). The median length of extended treatment was 89 days at a median cost of
      US$111 for drugs and US$32 for laboratory examinations. CONCLUSIONS: This study
      shows that extended treatment is common in one TB dispensary in Beijing. Further
      studies are needed to determine the countrywide prevalence of this practice and
      ascertain more conclusively the apparent lack of benefit.

PMID- 24864051
TI  - Dyslexic children suffer from less informative visual cues to control posture.
AB  - The goal of this study was to investigate the effects of manipulation of the
      characteristics of visual stimulus on postural control in dyslexic children. A
      total of 18 dyslexic and 18 non-dyslexic children stood upright inside a moving
      room, as still as possible, and looked at a target at different conditions of
      distance between the participant and a moving room frontal wall (25-150 cm) and
      vision (full and central). The first trial was performed without vision
      (baseline). Then four trials were performed in which the room remained stationary
      and eight trials with the room moving, lasting 60s each. Mean sway amplitude,
      coherence, relative phase, and angular deviation were calculated. The results
      revealed that dyslexic children swayed with larger magnitude in both stationary
      and moving conditions. When the room remained stationary, all children showed
      larger body sway magnitude at 150 cm distance. Dyslexic children showed larger
      body sway magnitude in central compared to full vision condition. In the moving
      condition, body sway magnitude was similar between dyslexic and non-dyslexic
      children but the coupling between visual information and body sway was weaker in
      dyslexic children. Moreover, in the absence of peripheral visual cues, induced
      body sway in dyslexic children was temporally delayed regarding visual stimulus.
      Taken together, these results indicate that poor postural control performance in
      dyslexic children is related to how sensory information is acquired from the
      environment and used to produce postural responses. In conditions in which
      sensory cues are less informative, dyslexic children take longer to process
      sensory stimuli in order to obtain precise information, which leads to
      performance deterioration.

PMID- 24864053
TI  - Depression and mood disorders among persons with autism spectrum disorders.
AB  - In the past decade, Autism Spectrum Disorders (ASD) have both risen in prevalence
      and become a critical area of research in the field of developmental
      disabilities. As the body of knowledge about ASD has grown, the overlap of ASD
      with other problems has also become a rapidly emerging area of study. One of the
      most studied of these topics is comorbid psychopathology, with depression and
      mood disorders emerging as one of the more troublesome of these co-occurring
      conditions. A great deal of research is still needed to determine how best to
      assess and treat these disorders within the context of ASD. This manuscript
      reviews current trends and topics relative to this area of study. 

PMID- 24864052
TI  - Habitual physical activity and cardiometabolic risk factors in adults with
      cerebral palsy.
AB  - Adults with cerebral palsy (CP) are known to participate in reduced levels of
      total physical activity. There is no information available however, regarding
      levels of moderate-to-vigorous physical activity (MVPA) in this population.
      Reduced participation in MVPA is associated with several cardiometabolic risk
      factors. The purpose of this study was firstly to compare levels of sedentary,
      light, MVPA and total activity in adults with CP to adults without CP. Secondly,
      the objective was to investigate the association between physical activity
      components, sedentary behavior and cardiometabolic risk factors in adults with
      CP. Adults with CP (n=41) age 18-62 yr (mean +/- SD=36.5 +/- 12.5 yr), classified
      in Gross Motor Function Classification System level I (n=13), II (n=18) and III
      (n=10) participated in this study. Physical activity was measured by
      accelerometry in adults with CP and in age- and sex-matched adults without CP
      over 7 days. Anthropometric indicators of obesity, blood pressure and several
      biomarkers of cardiometabolic disease were also measured in adults with CP.
      Adults with CP spent less time in light, moderate, vigorous and total activity,
      and more time in sedentary activity than adults without CP (p<0.01 for all).
      Moderate physical activity was associated with waist-height ratio when adjusted
      for age and sex (beta=-0.314, p<0.05). When further adjustment was made for total
      activity, moderate activity was associated with waist-height ratio (beta=-0.538,
      p<0.05), waist circumference (beta=-0.518, p<0.05), systolic blood pressure
      (beta=-0.592, p<0.05) and diastolic blood pressure (beta=-0.636, p<0.05).
      Sedentary activity was not associated with any risk factor. The findings provide
      evidence that relatively young adults with CP participate in reduced levels of
      MVPA and spend increased time in sedentary behavior, potentially increasing their
      risk of developing cardiometabolic disease.

PMID- 24864054
TI  - Spatio-temporal gait characteristics in children with Tourette syndrome: a
      preliminary study.
AB  - Earlier studies had suggested that variability of stride length in gait is a
      pathological sign of basal ganglia disease. Some evidence implicates the
      involvement of the basal ganglia and related thalamocortical circuitry in
      Tourette syndrome (TS). To date, the gait of subjects with TS has only discussed
      in case reports. This investigation compared the spatial and temporal gait
      characteristics of a sample of children with TS (N=8) with those of healthy
      controls (HC; N=8). All children were instructed to walk under two speed
      conditions: "preferred" and "fastest." Gait parameters were measured using an
      electronic walkway. Spatial and temporal gait parameters were compared using a
      two-way (group)*(conditions) repeated measures ANOVA. The preliminary results
      suggested that similar to HC children, children with TS were capable of
      regulating temporal characteristics of gait based on walking speed. They also
      exhibited subtle gait anomalies such as irregular step length, as evidenced by
      significant differences in step length differential (p=0.003), detectable despite
      the small sample size. These findings warrant further investigation into the gait
      control of children with TS. 

PMID- 24864055
TI  - Auditory localization and precedence effect: an exploratory study in infants and
      toddlers with visual impairment and normal vision.
AB  - The precedence effect is a spatial hearing phenomenon implicated in sound
      localization on reverberant environments. It occurs when a pair of sounds, with a
      brief delay between them, is presented from different directions; listeners give
      greater perceptual weight to localization cues coming from the first-arriving
      sound, called lead, and suppress localization cues from the later-arriving
      reflection, called lag. Developmental studies with sighted infants show that the
      first responses to precedence effect stimuli are observed at 4-5 months of life.
      In this exploratory study, we use the minimum audible angle (MAA) paradigm in
      conjunction with the observer-based psychophysical procedure to test the ability
      of infants and toddlers, with visual impairment and normal vision, to
      discriminate changes in the azimuthal position of sounds configured under
      precedence effect conditions. The results indicated that similar and, in some
      conditions, higher performances were obtained by blind toddlers when compared to
      sighted children of similar age, and revealed that the observer-based
      psychophysical procedure is a valuable method to measure auditory localization
      acuity in infants and toddlers with visual impairment. The video records showed
      auditory orienting behaviors specific of the blind children group. 

PMID- 24864056
TI  - Navigation within buildings: novel movement detection algorithms supporting
      people with visual impairments.
AB  - This study aimed at finding simple algorithms to identify three different
      movements registered by accelerometer and to detect differences in the
      acceleration signals of people with and without visual impairments. The Tactile
      Acoustical Navigation and Information Assistant (TANIA) is construed to provide
      persons suffering from visual impairments support for an independent navigation
      indoors and outdoors. Attaining this goal, TANIA uses vertical acceleration
      signal extrema to assess its user's walking distance. This study investigated
      first the sit-to-stand movement, stumbling and walking up- and down stairs of 25
      subjects with visual impairments using TANIA sensor system. The objective was to
      improve the user's movement detection using sensors to get valid and reliable
      data. In a second step of the study it was investigated if there is a difference
      between the above-mentioned movements in people with or without visual
      impairments (n=10). The acceleration signals of the subjects were compared. Three
      simple algorithms were found, which are able to separate the movement signals
      based on accelerometers of the respective daily movements. The second step
      analysis revealed a detectable difference in the second phase of stumbling
      (p=.034), where the subjects had to get back into walking forward. No differences
      in the other acceleration signals were found. 

PMID- 24864057
TI  - Altered trunk movements during gait in children with spastic diplegia:
      compensatory or underlying trunk control deficit?
AB  - Altered trunk movements during gait in children with CP are considered
      compensatory due to lower limb impairments, although scientific evidence for this
      assumption has not yet been provided. This study aimed to study the functional
      relation between trunk and lower limb movement deficits during gait in children
      with spastic diplegia. Therefore, the relationship between trunk control in
      sitting, and trunk and lower limb movements during gait was explored in 20
      children with spastic diplegia (age 9.2 +/- 3 yrs; GMFCS level I n=10, level II
      n=10). Trunk control in sitting was assessed with the Trunk Control Measurement
      Scale (TCMS), a clinical measure that reflects the presence of an underlying
      trunk control deficit. Trunk movements during gait were measured with a recently
      developed trunk model including the pelvis, thorax, head, shoulder line and
      spine. Lower limb movements were assessed with the Plug-in-Gait model
      (Vicon((r))). Range of motion (ROM) of the different trunk segments was
      calculated, as well as the Trunk Profile Score (TPS) and Trunk Variable Scores
      (TVSs). Similarly, the Gait Profile Score (GPS) and Gait Variable Scores (GVSs)
      were calculated to describe altered lower limb movements during gait. Correlation
      analyses were performed between the presence of impaired trunk control in sitting
      (TCMS) and altered trunk movements during gait (ROM, TPS/TVSs) and between these
      altered trunk movements and lower limb movements (GPS/GVSs) during gait. A poorer
      performance on the TCMS correlated with increased ROM and TPS/TVSs, particularly
      for the thorax, indicating the presence of an underlying trunk control deficit.
      No significant correlation was found between the TPS and GPS, suggesting that
      overall trunk and lower limb movement deficits were not strongly associated. Only
      few correlations between specific lower limb deficits (GVSs for hip ab/adduction,
      knee flexion/extension and ankle flexion/extension) and TVSs for thorax lateral
      bending and rotation were found. This study provided first evidence that the
      altered trunk movements observed during gait should not be solely considered
      compensatory due to lower limb impairments, but that these may also partially
      reflect an underlying trunk control deficit. A better understanding of underlying
      trunk control deficits in children with CP may facilitate targeted therapy
      planning and ultimately can optimize a child's functionality.

PMID- 24864058
TI  - Disrupted sensorimotor synchronization, but intact rhythm discrimination, in
      children treated for a cerebellar medulloblastoma.
AB  - The aim of this study was to investigate the temporal abilities of children
      treated by surgery for a malignant tumor in the cerebellum, both in the
      perception and the production of rhythm. Children with a diagnosed
      medulloblastoma and age-matched control children were tested in a rhythm
      discrimination task and a sensorimotor synchronization task. Their motor and
      cognitive capabilities were also assessed through a battery of age-adapted
      neuropsychological tests. The results did not show any significant difference in
      performance between groups for the discrimination task. On the contrary, children
      with cerebellar lesions produced longer and more variable inter-tap intervals
      (ITI) in their spontaneous motor tempo (SMT) than did the control children.
      However, the length and, to a lesser extent, the variability of their SMT
      decreased after a synchronization phase, when they had been instructed to tap in
      synchrony with a beep. During the synchronization task, the children with
      medulloblastoma succeeded to modify the length of their ITI in response to an
      auditory rhythm, although with better success when the inter-stimuli intervals
      (ISI) were shorter than when they were longer than the ITIs of their own SMT.
      Correlational analyses revealed that children's poorer synchronization
      performance was related to lower scores in neuropsychological tests assessing
      motor dexterity and processing speed. 

PMID- 24864059
TI  - Prevalence of actinic keratosis among dermatology outpatients in Austria.
AB  - BACKGROUND: Actinic keratoses (AKs) are common precursors of squamous cell
      carcinomas (SCCs) of the skin making them an important public health issue with
      information on their prevalence widely lacking. OBJECTIVES: To define the
      prevalence of AK in dermatology outpatients in Austria and to identify more
      accurately the target population for AK screening, treatment and prevention.
      METHODS: Each of the 48 randomly selected Austrian office-based dermatologists
      simultaneously screened 100 consecutive patients (aged >= 30 years) for the
      presence of AK. RESULTS: In total, 4449 evaluable patients showed an overall AK
      prevalence of 31.0%, which was higher in men (39.2%) than in women (24.3%) and
      increased with age in both sexes. AK distribution among sun-exposed body sites
      and extent of disease varied with sex and region. CONCLUSIONS: In Austria, AKs
      are common among dermatology outpatients, who have access to professional
      education and treatment. Investigations regarding the efficacy of routine AK
      screening in dermatology outpatients for the prevention of invasive SCC is
      warranted.

PMID- 24864061
TI  - Reply to Letter: Possibility of predicting neurological outcome using regional
      cerebral oxygen saturation (rSO2) after cardiac arrest.

PMID- 24864062
TI  - Possibility of predicting neurological outcome using regional cerebral oxygen
      saturation (rSO2) after cardiac arrest.

PMID- 24864064
TI  - Seek challenge.

PMID- 24864063
TI  - Changes to DA-CPR instructions: can we reduce time to first compression and
      improve quality of bystander CPR?
AB  - INTRODUCTION: Dispatcher-assisted CPR (DA-CPR) can increase rates of bystander
      CPR, survival, and quality of life following cardiac arrest. Dispatcher protocols
      designed to improve rapid recognition of arrest and coach CPR may increase
      survival by (1) reducing preventable time delays to start of chest compressions
      and (2) improving the quality of bystander CPR. METHODS: We conducted a
      randomized controlled trial comparing a simplified DA CPR script to a
      conventional DA CPR script in a manikin cardiac arrest simulation with lay
      participants. The primary outcomes measured were the time interval from call
      receipt to the first chest compression and the core metrics of chest compression
      (depth, rate, release, and compression fraction). CPR was measured using a
      recording manikin for the first 3 min of participant CPR. RESULTS: Of the 75
      participants, 39 were randomized to the simplified instructions and 36 were
      randomized to the conventional instructions. The interval from call receipt to
      first compression was 99 s using the simplified script and 124 s using the
      conventional script for a difference of 24s (p<0.01). Although hand position was
      judged to be correct more often in the conventional instruction group (88% versus
      63%, p<0.01), compression depth was an average 7 mm deeper among those receiving
      the simplified CPR script (32 mm versus 25 mm, p<0.05). No statistically
      significant differences were detected between the two instruction groups for
      compression rate, complete release, number of hands-off periods, or compression
      fraction. DISCUSSION: Simplified DA-CPR instructions to lay callers in simulated
      cardiac arrest settings resulted in significant reductions in time to first
      compression and improvements in compression depth. These results suggest an
      important opportunity to improve DA CPR instructions to reduce delays and improve
      CPR quality.

PMID- 24864066
TI  - From Matterhorn to Mt Everest: empowering rescuers and improving medical care in
      Nepal.
AB  - This article describes a private initiative in which professional Swiss rescuers,
      based at the foot of the Matterhorn, trained Nepalese colleagues in advanced high
      altitude helicopter rescue and medical care techniques. What started as a limited
      program focused on mountain safety has rapidly developed into a comprehensive
      project to improve rescue and medical care in the Mt Everest area for both
      foreign travelers and the local Nepalese people.

PMID- 24864065
TI  - Risk determinants of acute mountain sickness in trekkers in the Nepali Himalaya:
      a 24-year follow-up.
AB  - OBJECTIVE: Exposure to altitude may lead to acute mountain sickness (AMS) in
      nonacclimatized individuals. We surveyed AMS prevalence and potential risk
      factors in trekkers crossing a 5400-m pass in Nepal and compared the results with
      those of 2 similar studies conducted 12 and 24 years earlier. METHODS: In April
      2010, 500 surveys were distributed to English-speaking trekkers at 3500 m on
      their way to 5400 m, of which 332 (66%) surveys were returned complete. Acute
      mountain sickness was quantified with the Lake Louise Scoring System (LLSS,
      cutoff >=3 and >=5) and the Environmental Statistical Questionnaire III AMS-C
      score (ESQ-III, cutoff >=0.7). We surveyed demographics, body mass index (BMI),
      smoking habit, rate of ascent, awareness of AMS, and acetazolamide use. RESULTS:
      Prevalence of AMS was 22%, 23%, and 48% (ESQ-III >=0.7, LLSS >=5, and LLSS >=3,
      respectively) lower when compared with earlier studies. Risk factors for AMS were
      younger age, female sex, higher BMI, and smoking habit. Forty-two percent had
      elementary knowledge about the risk and prevention of AMS. Forty-four percent
      used acetazolamide. Trekkers took longer to climb from 3500 to 5400 m than in
      earlier studies. CONCLUSIONS: Prevalence of AMS continued to decline over a
      period of 24 years, likely as a result of slower ascent and increased use of
      acetazolamide. The AMS risk factors of younger age, female sex, and high BMI are
      consistent with prior studies. Awareness of risk and prevention of AMS remains
      low, indicating an opportunity to better educate trekkers and potentially further
      reduce AMS prevalence.

PMID- 24864067
TI  - Catastrophic acute ischemic stroke after Crotalidae polyvalent immune Fab (ovine)
      treated rattlesnake envenomation.
AB  - We report 2 cases of catastrophic ischemic stroke after Crotalidae polyvalent
      immune Fab (ovine)-treated rattlesnake envenomation, 1 fatal and the other
      resulting in significant permanent disability. It is possible these serious
      adverse events may have been related to venom factor(s), an interaction between
      venom and antivenom, occult patient blood dyscrasia, or to random unrelated
      events. We present the rationale for each possibility, and submit the experiences
      to elicit alternate postulation and communication of similar presentations.

PMID- 24864068
TI  - Human attacks by large felid carnivores in captivity and in the wild.
AB  - Whereas those who live in the native ranges of the large feline carnivores are
      well aware of the risks of cat and human encounters, North Americans and
      Europeans are increasingly exposed to exotic animals through travel, ecotourism,
      leisure pursuits in rural areas, occupational exposure, zoo and animal park
      visits, wild habitat encroachment at the urban-wildlands interface, and contact
      with exotic pets. In encounters during which persons have been severely injured,
      lapses in animal management protocols, lack of appropriate adult supervision, and
      intoxication have been reported. Unlike common domestic pets that have lived in
      close association with humans for thousands of years, no matter where individual
      large felines may have been raised, they remain wild carnivores with strong prey
      drive and territorial instincts. The emergency management of large felid attacks
      is similar to that of other major trauma: stabilization; management of
      significant orthopedic, neurologic, vascular, and soft tissue injuries;
      antibiotic coverage provided for the number of organisms that inhabit their
      mouths and the potential for tetanus and rabies; and early management in
      survivors of likely posttraumatic stress disorder. We must actively explore
      responsible measures globally that can be taken to ensure biologically
      appropriate, ethical, safe, and sustainable conservation of these large
      carnivores in both their natural habitats and captivity.

PMID- 24864069
TI  - Regarding the Wilderness Medical Society practice guidelines for heat-related
      illness.

PMID- 24864070
TI  - The importance of keeping cool: Reply regarding the Wilderness Medical Society
      practice guidelines for the prevention and treatment of heat-related illness.

PMID- 24864071
TI  - Correlation between bony changes measured with cone beam computed tomography and
      clinical dysfunction index in patients with temporomandibular joint
      osteoarthritis.
AB  - OBJECTIVES: To investigate the correlation between clinical dysfunction index
      (Di) and condylar bony changes, glenoid fossa bony changes and joint space
      changes. METHODS: Clinical data and cone beam computed tomography (CBCT) images
      of 240 patients with temporomandibular joint osteoarthritis (TMJ OA) were
      analyzed. The patients were assigned a score of Helkimo's clinical Di ranging
      from 1 to 25 and thereafter divided into 3 groups by the degree of Helkimo's Di.
      The condylar bony changes observed with CBCT were graded by the classification
      method of Koyama et al. Glenoid fossa bony changes and joint space changes were
      both classified as "positive" or "negative". Spearman's rank correlation test was
      used to correlate the score or degree of Helkimo's Di with the maximum condylar
      bony changes, glenoid fossa bony changes, and joint space changes. RESULTS: There
      was a significant correlation between the Helkimo's Di score and the maximum
      condylar bony changes (P <= 0.0001) and glenoid fossa bony changes (P <= 0.0001),
      and there was a poor correlation between the Helkimo's Di score and joint space
      changes (P = 0.184). Furthermore, there was a significant correlation between the
      degree of Helkimo's Di and the maximum condylar bony changes (P <= 0.0001) and
      glenoid fossa bony changes (P <= 0.0001), but there was a poor correlation
      between the degree of Helkimo's Di and joint space changes (P = 0.346).
      CONCLUSIONS: Both the score and degree of Helkimo's Di were highly correlated
      with maximum condylar changes and glenoid fossa bony changes, but not with joint
      space changes.

PMID- 24864072
TI  - Comparing calvarial transport distraction with and without radiation and fat
      grafting.
AB  - The purpose of this study is to: a) assess transport distraction to reconstruct
      cranial defects in radiated and non-radiated fields b) examine adipose grafting's
      effect on the bony regenerate and overlying wound, and c) elucidate sources of
      bone formation during transport distraction osteogenesis. Twenty-three male New
      Zealand white rabbits (3 months; 3.5 kg) were used, 10 non-irradiated and 13
      irradiated (17 treatment, 6 control) with a one-time fraction of 35 Gy. A 16 * 16
      mm defect was abutted by a 10 * 16 mm transport disc 5 weeks after irradiation,
      and 11 animals were fat grafted at the distraction site. Latency (1 day),
      distraction (1.5 mm/day), and consolidation (4 weeks) followed. Fluorochromes
      were injected subcutaneously and microCT, fluorescence, and histology assessed.
      In distracted animals without fat grafting, bone density measured 701.87 mgHA/ccm
      and 2271.95 mgHA/ccm in irradiated and non-irradiated animals. In distracted
      animals with fat grafting, bone density measured 703.23 mgHA/ccm and 2254.27
      mgHA/ccm in irradiated and non-irradiated animals. Fluorescence revealed
      ossification emanating from the dura, periosteum, and transport segment with
      decreased formation in irradiated animals. Transport distraction is possible for
      cranial reconstruction in irradiated fields but short-term osseous fill is
      significantly diminished. Adipose grafting enhances wound healing in previously
      irradiated fields but does not enhance ossification.

PMID- 24864073
TI  - Age and sex-related differences in 431 pediatric facial fractures at a level 1
      trauma center.
AB  - INTRODUCTION: Age and sex-related changes in the pattern of fractures and
      concomitant injuries observed in this patient population is helpful in
      understanding craniofacial development and the treatment of these unique
      injuries. The goal of this study was to examine all facial fractures occurring in
      a child and adolescent population (age 18 or less) at a trauma center to
      determine any age or sex-related variability amongst fracture patterns and
      concomitant injuries. METHODS: All facial fractures occurring at a trauma center
      were collected over a 12-year period based on International Classification of
      Disease, rev. 9 codes. This was delimited to include only those patients 18 years
      of age or younger. Age, sex, mechanism, and fracture types were collected and
      analyzed. RESULTS: During this time period, there were 3147 patients with facial
      fractures treated at our institution, 353 of which were in children and
      adolescent patients. Upon further review 68 patients were excluded due to
      insufficient data for analysis, leaving 285 patients for review, with a total of
      431 fractures. The most common etiology of injury was assault for males and motor
      vehicle accidents (MVA) for females. The most common fracture was of the mandible
      in males and of the orbit in females. The most common etiology in younger age
      groups includes falls and pedestrian struck. Older age groups exhibit a higher
      incidence of assault-related injuries. Younger age groups showed a propensity for
      orbital fractures as opposed to older age groups where mandibular fractures
      predominated. Intracranial hemorrhage was the most common concomitant injury
      across most age groups. CONCLUSION: The differences noted in etiology of injury,
      fracture patterns, and concomitant injuries between sexes and different age
      groups likely reflects the differing activities that each group engages in
      predominantly. In addition the growing facial skeleton offers varying degrees of
      protection to the cranial contents as force-absorbing mechanisms develop.

PMID- 24864074
TI  - Cephalometric and three-dimensional assessment of the posterior airway space and
      imaging software reliability analysis before and after orthognathic surgery.
AB  - PURPOSE: This study aimed to compare the reliability of three different imaging
      software programs for measuring the PAS and concurrently to investigate the
      morphological changes in oropharyngeal structures in mandibular prognathic
      patients before and after orthognathic surgery by using 2D and 3D analyzing
      technique. MATERIAL AND METHODS: The study consists of 11 randomly chosen
      patients (8 females and 3 males) who underwent maxillomandibular treatment for
      correction of Class III anteroposterior mandibular prognathism at the University
      Hospital in Zurich. A set of standardized LCR and CBCT-scans were obtained from
      each subject preoperatively (T0), 3 months after surgery (T1) and 3 months to 2
      years postoperatively (T2). Morphological changes in the posterior airway space
      (PAS) were evaluated longitudinally by two different observers with three
      different imaging software programs (OsiriX((r)) 64-bit, Switzerland;
      Mimics((r)), Belgium; BrainLab((r)), Germany) and manually by analyzing
      cephalometric X-rays. RESULTS: A significant increase in the upper airway
      dimensions before and after surgery occurred in all measured cases. All other
      cephalometric distances showed no statistically significant alterations.
      Measuring the volume of the PAS showed no significant changes in all cases. All
      three software programs showed similar outputs in both cephalometric analysis and
      3D measuring technique. CONCLUSION: A 3D design of the posterior airway seems to
      be far more reliable and precise phrasing of a statement of postoperative
      gradients than conventional radiography and is additionally higher compared to
      the corresponding manual method. In case of Class III mandibular prognathism
      treatment with bilateral split osteotomy of the mandible and simultaneous
      maxillary advancement, the negative effects of PAS volume decrease may be reduced
      and might prevent a developing OSAS.

PMID- 24864077
TI  - Addicted mothers to be criminalized in Tennessee.
AB  - In April 2014 Tennessee acted to criminalize pregnant women who use illegal drugs
      and have an offspring "considered harmed". We discuss seven major reasons why
      this law is wrong and dangerous.  Criminalizing vulnerable, addicted mothers
      scare them away from treatment. The new law will practically target the poor,
      vulnerable, uninsured non-white pregnant woman. It is hoped that, similar to
      previous cases, the American justice system will once again reverse the decision
      and allow the true American values to prevail. 

PMID- 24864076
TI  - Association between the level of antibodies in bulk tank milk and bovine
      respiratory syncytial virus exposure in the herd.
AB  - Antibody levels in bulk tank milk (BTM) against bovine respiratory syncytial
      virus (BRSV) are used to classify BRSV status of herds. The aim of this study was
      to investigate how these levels correspond with the time at which the herds were
      infected. Bulk tank milk, individual milk and serum samples from cows and young
      stock were investigated using an indirect ELISA. Screenings of BTM from 89 dairy
      herds during two winter seasons revealed a prevalence of positive herds from 82
      per cent to 85 per cent. Eleven herds showed a marked increase in antibody levels
      between two screenings, indicating new infection. However, two of these herds had
      been free from BRSV for the last five to seven years. Two newly infected herds
      were monitored for four years and did not appear to get reinfected. Surprisingly,
      the BTM antibody levels in these herds remained high throughout the study period,
      but fluctuated significantly. This shows that the levels of antibodies in BTM can
      remain high for several years, even in herds where reinfection does not occur.
      BTM serology is a useful tool in the monitoring of infectious diseases in dairy
      herds, but has limitations as a diagnostic tool for BRSV infections. 

PMID- 24864075
TI  - Defining the role of Porphyromonas gingivalis peptidylarginine deiminase (PPAD)
      in rheumatoid arthritis through the study of PPAD biology.
AB  - BACKGROUND: Antibodies to citrullinated proteins are a hallmark of rheumatoid
      arthritis (RA). Porphyromonas gingivalis peptidylarginine deiminase (PPAD) has
      been implicated in the initiation of RA by generating citrullinated neoantigens
      and due to its ability to autocitrullinate. OBJECTIVES: To define the
      citrullination status and biology of PPAD in P gingivalis and to characterise the
      anti-PPAD antibody response in RA and associated periodontal disease (PD).
      METHODS: PPAD in P gingivalis cells and culture supernatant were analysed by
      immunoblotting and mass spectrometry to detect citrullination. Recombinant PPAD
      (rPPAD), inactive mutant PPAD (rPPAD(C351S)), and N-terminal truncated PPAD
      (rPPAD(Ntx)) were cloned and expressed in Escherichia coli. Patients with RA and
      healthy controls were assayed for IgG antibodies to citrullinated rPPAD and
      unmodified rPPAD(C351S) by ELISA. Anti-PPAD antibodies were correlated with anti
      cyclic citrullinated peptide (third-generation) antibody levels, RA disease
      activity and PD status. RESULTS: PPAD from P gingivalis is truncated at the N
      terminal and C-terminal domains and not citrullinated. Only when artificially
      expressed in E coli, full-length rPPAD, but not truncated (fully active)
      rPPAD(Ntx), is autocitrullinated. Anti-PPAD antibodies show no heightened
      reactivity to citrullinated rPPAD, but are exclusively directed against the
      unmodified enzyme. Antibodies against PPAD do not correlate with anti-cyclic
      citrullinated peptide levels and disease activity in RA. By contrast, anti-PPAD
      antibody levels are significantly decreased in RA patients with PD. CONCLUSIONS:
      PPAD autocitrullination is not the underlying mechanism linking PD and RA. N
      terminal processing protects PPAD from autocitrullination and enhances enzyme
      activity. Anti-PPAD antibodies may have a protective role for the development of
      PD in patients with RA.

PMID- 24864080
TI  - Balancing the risks of stent thrombosis and major bleeding during primary
      percutaneous coronary intervention.

PMID- 24864081
TI  - Application of microcomputed tomography for quantitative analysis of dental root
      canal obturations.
AB  - INTRODUCTION: The aim of the study was to apply microcomputed tomography to
      quantitative evaluation of voids and to test any specific location of voids in
      tooth's root canal obturations. MATERIALS AND METHODS: Twenty root canals were
      prepared and obturated with gutta-percha and Tubli-Seal sealer using the
      thermoplastic compaction method (System B+Obtura II). Roots were scanned and
      three-dimensional visualization was obtained. The volume and Feret's diameter of
      I-voids (at the filling/dentine interface) and S-voids (surrounded by filling
      material) were measured. RESULTS: The results revealed that none of the scanned
      root canal fillings were void-free. For I-voids, the volume fraction was
      significantly larger, but their number was lower (P=0.0007), than for S-voids.
      Both types of voids occurred in characteristic regions (P<0.001). I-voids
      occurred mainly in the apical third, while S-voids in the coronal third of the
      canal filling. CONCLUSIONS: Within the limitations of this study, our results
      indicate that microtomography, with proposed semi-automatic algorithm, is a
      useful tools for three-dimensional quantitative evaluation of dental root canal
      fillings. In canals filled with thermoplastic gutta-percha and Tubli-Seal, voids
      at the interface between the filling and canal dentine deserve special attention
      due to of their periapical location, which might promote apical microleakage.
      Further studies might help to elucidate the clinical relevance of these results.

PMID- 24864082
TI  - [Rare clinical form of glioblastoma multiforme].
AB  - Glioblastoma multiforme (glioblastoma multiforme - GBM) is the most malignant
      tumor classified by WHO. It is also the most common primary CNS tumor with a very
      aggressive course and unfavourable prognosis, usually develops in adults, and is
      typically located supratentorially in the fronto-temporal region. However, the
      literature describes an unusual position of GBM (e.g. spinal cord, pons, pineal
      region), familial gliomas unconnected with the family of gliomas predisposed to
      the occurrence of syndromes, unusual glioma and metastatic sites, gliomas
      transplanted with organs. In this paper, based on the available literature, the
      authors discuss an unusual and rare form of glioblastoma multiforme. 

PMID- 24864078
TI  - Importance of frailty in patients with cardiovascular disease.
AB  - Cardiovascular diseases (CVDs) are the leading cause of morbidity and mortality.
      With the ageing population, the prognostic determinants among others include
      frailty, health status, disability, and cognition. These constructs are seldom
      measured and factored into clinical decision-making or evaluation of the
      prognosis of these at-risk older adults, especially as it relates to high-risk
      interventions. Addressing this need effectively requires increased awareness and
      their recognition by the treating cardiologists, their incorporation into risk
      prediction models when treating an elderly patient with underlying complex CVD,
      and timely referral for comprehensive geriatric management. Simple measures such
      as gait speed, the Fried score, or the Rockwood Clinical Frailty Scale can be
      used to assess frailty as part of routine care of elderly patients with CVD. This
      review examines the prevalence and outcomes associated with frailty with special
      emphasis in patients with CVD.

PMID- 24864083
TI  - [The role of diet in multiple sclerosis].
AB  - Multiple sclerosis is a demyelinating disease of the central nervous system,
      occurs most commonly in adults between 20 and 40 years of age. Etiology of this
      disease is still not known, and one of the analyzed environmental factors is
      food. In this study, based on literature, discusses the impact of dietary intake
      of food on the occurrence and development of the disease. This study demonstrated
      that patients with multiple sclerosis less than healthy people ate bread and
      cereal products, fish, some vegetables and fruits. While patients often consumed
      an animal products, whole milk and sweets. It also discusses Swank's diet, which
      suggest that the severity of symptoms disease may be responsible food of animal
      origin, which is rich in saturated fatty acids. The author found that patients
      who comply a diet, after 34 years of application, the risk of death due to
      multiple sclerosis was three times lower than in those who have not complied with
      all the dietary recommendations. Moreover, research demonstrated a correlation
      between deficiency of omega-3, vitamin D, B12, antioxidant vitamins and folic
      acid in diet, and the development and exacerbation of symptoms of multiple
      sclerosis. Results of research concerning the relationship between dietary
      factors and the occurrence and development of this disease are inconclusive why
      the need is greater the amount thereof in this field. Patients may consider using
      a diet or supplements, if pharmacotherapy and other alternative and complementary
      methods do not bring expected effects. 

PMID- 24864084
TI  - [Stearoyl-CoA desaturase--the lipid metabolism regulator].
AB  - Stearoyl-CoA desaturase is an enzyme from the class of oxidoreductase, which
      catalyzes the formation of a fatty acid double bond between C9 and C10. It plays
      a key role in composition of the fatty acid profile in adipose tissue and animal
      products such as meat and milk. Additionally, it is an important regulator of
      metabolic processes in the body, and it determines the maintenance of energy
      homeostasis. This enzyme is encoded by an SCD gene, which, depending on the
      species, may exist as different isoforms. mRNA expression of stearoyl-CoA
      desaturase is dependent on many factors, including diet, hormones, and the
      activity of other genes. In previous studies, several mutations were
      characterized within the sequence of Delta9-desaturase, which may affect the
      activity of the protein in the tissues, as well as the value of breeding animals.
      Effects of particular mutations of the gene encoding the enzyme appears to be
      particularly important for diseases associated with obesity, diabetes,
      hypertension, heart diseases or cancer in humans. Also, it seems that using sheep
      as a potential animal model could be helpful in uncovering and understanding the
      mechanisms regulated by stearoyl-CoA desaturase. 

PMID- 24864085
TI  - Is TCF7L2 variant associated with non-diabetic chronic kidney disease
      progression? Results of a family-based study.
AB  - INTRODUCTION: It is assumed that genetic factors may play a significant role in
      CKD development. The aim of the study was to investigate the role of rs7903146
      polymorphism in the TCF7L2 gene in development and progression of non-diabetic
      chronic kidney disease (CKD). MATERIAL/METHODS: 109 children and young adults
      with CKD caused by primary glomerulopathy and tubulointerstitial nephropathy,
      stages 3-5, and their 218 biological parents with no renal dysfunction were
      included in the study. We tested the transmission of alleles of rs7903146
      polymorphism in the TCF7L2 gene from heterozygous parents to offspring affected
      with CKD using the transmission/disequilibrium test. We also analysed whether
      rs7903146 polymorphism had any impact on the loss of glomerular filtration rate.
      RESULTS: The rs7903146 polymorphism in TCF7L2 allele transmission from
      heterozygous parents to their affected children was not different from a random
      proportion expected for no association, in the whole group of subjects, and in
      the subgroups, depending on CKD aetiology. Lack of association between the
      analysed polymorphism and the loss of glomerular filtration rate was found in the
      total group of patients as well as in the subgroups, regarding the cause of CKD.
      CONCLUSIONS: This study found no association between rs7903146 polymorphism in
      the TCF7L2 gene and the increased risk for development of CKD caused by primary
      glomerulopathy and analysed tubulointerstitial nephropathy. The progression rate
      of CKD of non-diabetic aetiology does not depend on this polymorphism.

PMID- 24864079
TI  - Anti-inflammatory therapies for cardiovascular disease.
AB  - Atherothrombosis is no longer considered solely a disorder of lipoprotein
      accumulation in the arterial wall. Rather, the initiation and progression of
      atherosclerotic lesions is currently understood to have major inflammatory
      influences that encompass components of both the innate and acquired immune
      systems. Promising clinical data for 'upstream' biomarkers of inflammation such
      as interleukin-6 (IL-6) as well as 'downstream' biomarkers such as C-reactive
      protein, observations regarding cholesterol crystals as an activator of the IL
      1beta generating inflammasome, and recent Mendelian randomization data for the IL
      6 receptor support the hypothesis that inflammatory mediators of atherosclerosis
      may converge on the central IL-1, tumour necrosis factor (TNF-alpha), IL-6
      signalling pathway. On this basis, emerging anti-inflammatory approaches to
      vascular protection can be categorized into two broad groups, those that target
      the central IL-6 inflammatory signalling pathway and those that do not. Large
      scale Phase III trials are now underway with agents that lead to marked
      reductions in IL-6 and C-reactive protein (such as canakinumab and methotrexate)
      as well as with agents that impact on diverse non-IL-6-dependent pathways (such
      as varespladib and darapladib). Both approaches have the potential to benefit
      patients and reduce vascular events. However, care should be taken when
      interpreting these trials as outcomes for agents that target IL-6 signalling are
      unlikely to be informative for therapies that target alternative pathways, and
      vice versa. As the inflammatory system is redundant, compensatory, and crucial
      for survival, evaluation of risks as well as benefits must drive the development
      of agents in this class. 

PMID- 24864086
TI  - [Mycolic acids--biological role and potential application in Mycobacterium
      detection and differentiation].
AB  - Mycolic acids are one of the basic structural elements of the cell wall of
      bacteria from Corynebacterineae suborder. These compounds are long-chain alpha
      hydroxy beta-alkyl fatty acids with two hydrocarbon chains: longer meromycolic
      and shorter alpha-chain meromycolic alpha-chain. The genus Mycobacterium is
      characterized by the presence of mycolic acids in length from 60 to 90 carbon
      atoms having a fully saturated alpha-chain with a defined length of 22, 24 or 26
      carbon atoms. Current research indicates that not only the presence of mycolic
      acids in the cell wall of mycobacteria is essential for the virulence of
      mycobacteria. It is proved that the relationship between different types of
      mycolic acids, their length and the degree of cyclopropanation may vary depending
      on the stage of infection and mycobacterial culture conditions. At the same time
      it has been shown that some mycolic acid types are crucial for biofilm formation,
      antimycobacterial drug resistance or interactions with the immune system. Recent
      studies also indicate that analysis of mycolic acid profiles could be an
      alternative to conventional methods of diagnosis of diseases such as
      tuberculosis, leprosy or mycobacteriosis. 

PMID- 24864087
TI  - [Vitamin D--a new look in medicine and rheumatology].
AB  - The research of the last decade pointed to the importance of vitamin D not only
      in bone metabolic processes, but also in immunologic and anticarcinogenic
      processes. Thus, its common insufficiency is related to serious health
      consequences--e.g. increased mortality and morbidity caused by autoimmune and
      cancer diseases. The modification of the range of values of vitamin D serum
      concentration and revision of its nutritional and pharmacological recommendations
      are suggested nowadays. Moreover, the discovery of the vitamin D receptor (VDR)
      enables us to understand its influence on other organs. To date the new
      properties of vitamin D are elucidated in the literature showing its preventive
      effect and possible application in supportive treatment of many diseases.

PMID- 24864088
TI  - [Allergens of mites].
AB  - Mite allergens belong to the group of inhalant allergens and represent antigenic
      substances which are particutlarly important in the pathogenesis of respiratory
      system diseases and skin diseases. The most common diseases associated with
      chronic exposure to these aeroallergens include: allergic rhinitis, bronchial
      asthma and atopic dermatitis. Mite allergens are simple proteins or glycoproteins
      with different molecular structures and various biochemical functions. The
      sensitizing capacity of these proteins is connected from their physicochemical
      properties. Individual allergens perform, among others, the functions of
      structural proteins, act as enzymes, transport lipids, bind metal ions, and are
      capable of glycosylation. In addition, mite allergenic proteases degrade proteins
      of the skin epithelium-resulting in a weakening of its natural protective barrier
      and induce the immune response. The proteases also induce the release of pro
      inflammatory cytokines: interleukin-4 (IL-4), interleukin 6 (IL-6), interleukin 8
      (IL-8), eotaxin, and granulocyte-macrophage colony-stimulating factor-GM-CSF. The
      article presents the tertiary structure of major and mid-range mite allergens and
      their classification. Based on literature reports concerning the chemical
      structure of allergenic proteins, it was emphasized that the structural
      differences between homologous proteins with allergenic pozoproperties relate to
      the distribution of amino acid residues on the surface of the molecule. IgE
      binding affinity and the similarities and differences in the amino acid sequence
      of the allergens were also the basis for determining cross-reactivity of
      allergenic proteins. The paper shows an example of this phenomenon, describing
      the existence of common allergens for various mite species. 

PMID- 24864089
TI  - [Dysregulation of the mTOR signaling pathway in the pathogenesis of autism
      spectrum disorders].
AB  - Mammalian target of rapamycin (mTor) plays multiple role in central nervous
      system and is involved in regulation of cell viability, differentiation,
      transcription, translation, protein degradation, actin cytoskeletal organization
      and autophagy. Recent experimental and clinical studies reveal that disturbances
      of mTOR signaling are involved in the pathogenesis of autism spectrum disorders
      (ASD). This article reviews current data on the alteration in the mTOR
      transduction cascade, which may contribute to common neurobehavioral disorders
      typical for ASD. Moreover, the results of the latest experimental studies on the
      potential of mTOR inhibitors for the treatment of ASD are reviewed. 

PMID- 24864090
TI  - [The formation, metabolism and the evolution of blood platelets].
AB  - Platelets are the smallest, depleted of nucleus blood cells which contain a
      typical cellular organelles including the mitochondria, so that have active
      metabolism. Platelets possess the highly organized cytoskeleton, specific
      secretory granules and unique membrane receptors system responsible for their
      high reactivity. The key role of blood platelets is to maintain normal
      hemostasis, but they also play important roles in inflammation, immune processes
      and the cancer progression. The anucleated, small platelets occur in
      representatives of all clusters of mammals, so it seems to be an adaptation
      feature. In other vertebrates similar hemostatic functions are played by large
      nucleated platelets, which are much more weakly reactive. Small, reactive
      platelets, appearing in the evolution of mammals, allowed the formation of clots
      faster and slower blood loss in case of injury, but also increased the risk of
      thromboembolic and cardiovascular diseases. Daily the human body forms about
      1x1011 platelets, which are produced by a process of differentiation, maturation
      and fragmentation of the cytoplasm of mature megakaryocytes. The emergence of
      platelets is the final stage of megakaryocyte differentiation and is followed by
      formation of the direct precursors called proplatelets. The anucleated platelets
      are regarded as terminally differentiated cells, which are not capable of further
      cell division. However, despite the absence of a nucleus, in blood platelets the
      synthesis and transcription of mitochondrial DNA and protein synthesis occurring
      on the basis of mRNA from megakaryocytes has been confirmed. However, recent
      studies published in 2012 show that the platelets are capable not only of the
      process of protein synthesis, but also of generation of new cells, which are
      functionally and structurally similar to the parent platelets.

PMID- 24864091
TI  - [The importance of putrescine in the human body].
AB  - Putrescine plays a very important role in the regulation of division,
      differentiation and maturation of cells as well as apoptosis. As the polycationic
      molecule it stabilizes the structure of DNA and participates in the functioning
      of cell membranes. It is able to interact with series of ion channels and has
      affinity for many receptors. The article presents the participation of putrescine
      in the metabolism of iron and mechanism of its transport across biological
      membranes. Especially important for the homeostasis of putrescine has ornithine
      decarboxylase and availability of its substrate--ornithine. Affecting to this
      enzyme is the simplest and widely used method of controlling the concentration of
      putrescine. For this purpose its inhibitor-eflornithine is applied. There was
      also a number of other enzymes involved in the metabolism of putrescine that was
      presented. Current information about the clinical relevance of putrescine in
      infertility, embryonic development, hirsutism, epilepsy, Alzheimer's disease,
      Parkinson's disease, prevention of metastases and hemostasis was also described.
      These processes were presented, in which putrescine plays a major role and
      focused on the latest reports. Attention was drawn to the situations where it has
      beneficial effects and those in which it is the cause of the pathology. Some of
      the cited reports are in phase of speculation on the possible use of it, but a
      significant part is already confirmed and used in clinical practice. The facts
      presented in this article show how great is the meaning of putrescine and how
      important role this simple specimen plays in the metabolic processes of living
      organisms.

PMID- 24864092
TI  - [The role of immune system cells and their receptors in viral infections-
      selected data].
AB  - The study of the immune system started about a hundred years ago with the
      phagocytosis experiments of Mechnikov. That which is now referred to as non
      specific cell-mediated immunity was quickly linked to studies related to, inter
      alia, the immunity determined by antibodies (humoral), which has long been
      considered as the first line of defense against diseases caused by micro
      organisms, including viruses. Despite their small size, viruses have a huge
      impact on the host, as they produce substances that stimulate the antiviral
      response and affect it. The paper presents selected data on participation of
      immune system cells and their receptors in viral infections, as the host cells
      have evolved a number of specific cellular and humoral components of the
      signaling networks that are involved in the detection and the host's response to
      viral infections. 

PMID- 24864093
TI  - [MicroRNA--a new diagnostic tool in coronary artery disease and myocardial
      infarction].
AB  - Coronary artery disease remain one of the leading causes of mortality in the
      world, indicating the need for innovative therapies and diagnosis for heart
      disease. MicroRNAs (miRNAs) have recently emerged as one of the central players
      in regulating gene expression which implicatate in normal cardiac development and
      many pathological process of the cardiovascular system, including cardiac
      arrhythmia, heart failure, cardiac fibrosis, coronary artery disease and
      myocardial infarction. iRNA are small noncoding RNAs 18-23 nucleotides in length
      that regulate expression of target genes through sequence-specific hybridization
      to the 3' untranslated region of messenger RNAs and block translation. miRNAs are
      not only found intracellularly, but also detectable outside cells, including
      various body fluids (i.e. serum, plasma, saliva, urine). This review will
      highlight recent findings in the regulation of miRNA biogenesis and secretion,
      modulation of the cardiovascular pathological process in CAD and AMI and the
      potential as non-invasive biomarkers for cardiac ischemia. 

PMID- 24864094
TI  - [Chlamydiosis of urogenitary tract in humans].
AB  - Chlamydiae are bacteria commonly found in the environment of human life and they
      cause many diseases. Chlamydial infections are common among men and women,
      although they are more often diagnosed in women and they are frequently
      asymptomatic, due to the biology of chlamydiae. Incorrectly diagnosed and
      untreated, they cause many complications which can lead to infertility in both,
      men and women. This work presents the diseases caused by chlamydiae of the
      urogenitary tract, including environmental chlamydiae, so far in Polish
      literature rarely presented, which extends the panel responsible for chlamydial
      genital tract disease, particularly in women. A major problem is that the
      knowledge of the immune mechanisms that occur in the case of infection with these
      bacteria, especially in view of prevention of these infection, mainly in the
      context of creation of the vaccine. Also important fact from the knowledge of
      immunity in chlamydiosis is base for diagnosis of these infection. 

PMID- 24864095
TI  - [Interferons: between structure and function].
AB  - Interferons are a family of proteins that are released by a variety of cells in
      response to infections caused by viruses. Currently, we distinguish three types
      of interferons. They are classified based on the nucleotide sequence, interaction
      with specific receptors, chromosomal location, structure and physicochemical
      properties. The following interferons are classified as type I: alpha, beta,
      omega, kappa, epsilon, zeta, tau, delta, nu. They are recognized and bound by a
      receptor formed by two peptides, IFN-alphaR1 and IFN-alphaR2. Representative of
      type II interferons is interferon-gamma. It binds to a receptor composed of
      chains IFNGR-1 and IFNGR-2. The recently classified type III interferons comprise
      IFN-lambda1, IFN-lambda2, and IFN-lambda3. They act on receptors formed by
      lambdaR1 IFN-and IL-10R2 subunits. A high level of antiviral protection is
      achieved by IFN-alpha, IFN-beta and IFN-lambda. Antiviral activity of interferons
      is based on the induction and regulation of innate and acquired immune
      mechanisms. By binding to transmembrane receptors, IFN interacts with target
      cells mainly by activating the JAK/STAT, but also other signaling pathways. This
      leads to induction and activation of many antiviral agents, such as protein
      kinase RNA-activated (PKR), ribonuclease 2-5A pathway, and Mx proteins, as well
      as numerous apoptotic pathways. As a result of the protective effect of
      interferons, the virus binding to cells and viral particles penetration into
      cells is stopped, and the release of the nucleocapsid from an envelope is
      suppressed. Disruption of transcription and translation processes of the
      structural proteins prevents the formation of virions or budding of viruses, and
      as a result degradation of the viral mRNA; the started processes inhibit the
      chain synthesis of viral proteins and therefore further stimulate the immune
      system cells. 

PMID- 24864096
TI  - [Meropenem--therapeutic recommendation after twenty years of presence on
      pharmaceutical market].
AB  - Meropenem is the first representative of carbapenem analogues with methyl group,
      which has been applied in medicine. This drug has been approved by FDA (Food and
      Drug Administration) in 1996. Available results of clinical trials and scientific
      reports point surprising synergism of combination of meropenem with other
      chemotherapeutics, in the treatment of bacterial diseases. Present study based on
      available information presents indications for use the mentioned antibiotic in
      pharmacotherapy of infectious diseases. Meropenem is the first representative of
      carbapenem analogues, which contains methyl group. Introduction of a methyl group
      at the system of coupled rings: beta-lactam and pyrrolidine, solved the problem
      of degradation by the dehydropeptidase-I (DHP-I). In the consequence it is not
      necessary to use meropenem in the connection with specific DHP-I inhibitors.
      Meropenem, similarly to other carbapanem analogues, is intended for the treatment
      of severe inpatient and outpatient infections. Bacterial resistance to meropenem
      may be the result of: carbapenemases activity, decreased affinity to Penicillin
      Binding Proteins--PBP (mainly PBP 2 and PBP 3) and activation of efflux pump
      (antibiotic ejection outside the cell). Twenty-year period of application of
      meropenem in pharmacotherapy may cause the spread of methyl-beta-lactamases.

PMID- 24864097
TI  - [The advanced oxidation protein products as potential diagnostic and prognostic
      factor in diseases of the indicated participation of oxidative stress].
AB  - The possibility of diagnostic and/or prognostic use of measuring the
      concentration of advanced oxidation protein products (AOPPs) in chronic diseases
      with well-documented involvement of oxidative stress (OS) in their pathogenesis
      were the subject of numerous studies. In the present study discussed the
      pathological conditions and disorders, in which the role of OS and oxidative
      damage of proteins is also indicated as one of the factors in their
      etiopathogenesis. The presented data concerned clinical and diagnostic aspects of
      AOPPs as well as biochemical mechanisms of disturbances in the infection and
      autoimmune diseases, cancers, genetic and neurological diseases. Participation of
      AOPPs in disturbances connected with fertility, pregnancy delivery and
      prematurity are also shown. Moreover the single literature data concerning other
      pathological states, in which AOPPs are also becoming the object of intensive
      investigations are presented. The review and application possibilities of AOPPs
      measurement as useful marker for diagnosis, prognosis and monitoring the course
      of these diseases were performed. Diagnostic or prognostic utility of AOPPs are
      especially indicated in the course of rheumatoid arthritis, development of
      pregnancy complication both in mother and child, and dementia. However, AOPPs
      measurement seems to be most promising in plasma or urine in course of cancer
      diseases. 

PMID- 24864098
TI  - [The role of the Fanconi anemia pathway in DNA repair and maintenance of genome
      stability].
AB  - The Fanconi anemia (FA) pathway is one of the DNA repair systems involved in
      removal of DNA crosslinks. Proteins which belong to this pathway are crucial to
      the protection of genetic information, whereas disturbances in their function
      have serious implications for the whole organism. Biallelic mutations in FA genes
      are the cause of Fanconi anemia - a genetic disease which manifests itself
      through numerous congenital abnormalities, chromosomal instability and increased
      predisposition to cancer. The FA pathway is composed of fifteen proteins. Eight
      of them, in the presence of DNA interstrand crosslinks (ICLs), form a nuclear
      core complex responsible for monoubiquitination of FANCD2 and FANCI, which is a
      key step of ICL repair. FA proteins which are not involved in the
      monoubiquitination step participate in repair of DNA double strand breaks via
      homologous recombination. Some of the FA proteins, besides having a direct role
      in the repair of DNA damage, are engaged in replication, cell cycle control and
      mitosis. The unperturbed course of those processes determines the maintenance of
      genome stability. 

PMID- 24864099
TI  - [Applications of electromagnetic radiation in medicine].
AB  - Recent decades have been devoted to the intense search for the response to
      questions related to the impact of radiation on the human body. Due to the
      growing fashion for a healthy lifestyle, increasing numbers of works about the
      alleged dangers of electromagnetic waves and diseases that they cause appeared.
      However, the discoveries of 20th century, and knowledge of the properties of
      electromagnetic radiation have allowed to broaden the horizons of the use of
      artificial sources of radiation in many fields of science and especially in
      medicine. The aim of this paper is to show that although excessive radiation or
      high doses are dangerous to the human body, its careful and controlled use, does
      not pose a threat, and it is often necessary in therapy. The possibility of using
      ionizing radiation in radiotherapy, isotope diagnostics or medical imaging, and
      non-ionizing radiation in the treatment for dermatological disorders and cancers
      will be presented. The unique properties of synchrotron radiation result in using
      it on a large scale in the diagnosis of pathological states by imaging methods. 

PMID- 24864100
TI  - [Cardiotoxicity as undesired side effect in the treatment of breast cancer].
AB  - Improvement of methods used in breast cancer therapy resulted in increased
      treatment effectiveness and prolonged survival of patients. However, this is
      accompanied by increased frequency of adverse side effects, including cardiac
      toxicity, which is becoming a serious problem affecting the quality of life and
      overall survival of cancer patients. The risk of developing cardiovascular
      complications depends on the type and dose of therapeutic agent used. The highest
      risk of cardiotoxicity is associated with anthracyclines. They are used
      frequently in cancer therapy due to their high efficiency but show a dose
      dependent toxicity to the cardiovascular system. Cardiotoxicity can also occur
      with other substances used in breast cancer chemotherapy, as well as with
      radiotherapy. Combining potentially cardiotoxic therapeutic agents, commonly used
      in combination therapy, may result in escalation of toxic side effects.
      Mechanisms of heart damage are different for various cardiotoxic agents, but
      symptoms usually involve heart failure, ischemic heart disease, arrhythmias,
      hypertension, valvular diseases or pericarditis and myocarditis. The practices
      used to reduce the risk of cardiotoxic effects of cancer therapy include
      evaluation of cardiac functions before treatment and constant monitoring during
      and after treatment. Furthermore, limited doses and modifications of anticancer
      agent administration patterns are employed, as well as simultaneous application
      of cardioprotective agents. Understanding of cardiotoxic mechanisms of agents
      used in breast cancer treatment can help to develop efficient cardioprotective
      substances. Because oxidative stress plays an important role in the toxicity of
      cancer therapy, compounds with antioxidant properties are a very promising target
      of research. 

PMID- 24864101
TI  - Quality of life in patients with cystic fibrosis depending on the severity of the
      disease and method of its treatment.
AB  - INTRODUCTION: Quality of life is a measure not only of disease severity and its
      functional impact (physical, psychological, and social functioning) but also the
      efficacy of novel therapies. The aim of this study was to analyze the quality of
      life in cystic fibrosis patients depending on the severity of the disease and
      methods of its treatment. MATERIAL/METHODS: The study included groups of cystic
      fibrosis patients: 1) after lung transplantation, 2) requiring chronic oxygen
      therapy, and 3) in stable clinical status. Forty-five men and women older than 18
      years were enrolled. The participants were examined with the Polish version of
      the Cystic Fibrosis Quality of Life Questionnaire (CFQoL) adapted by Debska &
      Mazurek. RESULTS: Patients from analyzed groups differed significantly in terms
      of their quality of life in most of the subscales included in CFQoL, but not in
      Future Concerns and Interpersonal Relationships. DISCUSSION: Although lung
      transplantation markedly improves the quality of life of patients with cystic
      fibrosis, they still experience problems with social functioning and future
      concerns.

PMID- 24864102
TI  - [Role of the Hippo pathway in cell proliferation and organ size control.
      Disorders of the pathway in cancer diseases].
AB  - The Hippo pathway (also known as SWH--Salvador/Warts/Hippo), discovered for the
      first time in Drosophila melanogaster, is responsible for cell proliferation and
      organ size control in mammalian systems. The components of the pathway are two
      kinases and their adaptor proteins which inhibit the transcription co-activator
      YAP by phosphorylation. When the pathway is inactive (as an effect of upstream
      component gene expression disorders), activated YAP is translocated to the
      nucleus where it cooperates with TEAD transcription factor and promotes
      expression of genes that regulate cell proliferation and apoptosis. YAP acts
      generally as an oncogene, although there are some reports describing its role as
      a tumor suppressor. Since all of the core components are well known, the latest
      reports provide mostly information about upstream components of the Hippo pathway
      or its interaction with other biochemical pathways. Because of the Hippo
      pathway's role in the cell cycle, it has become a very attractive object for
      studies of the genetic background of cancer. The under- or overexpression of
      genes involved in the Hippo pathway has been described in many different types of
      cancers. Moreover, it has been shown that there is a strong connection between
      cancer cell phenotype and highly activated YAP presence in the nucleus. This
      paper reviews the most important data about Hippo pathway regulation in
      Drosophila and mammals, including its numerous disorders and their implications
      for cell function.

PMID- 24864103
TI  - [Interactions of proliferation and differentiation signaling pathways in
      myogenesis].
AB  - The commitment of myogenic cells in skeletal muscle differentiation requires
      earlier irreversible interruption of the cell cycle. At the molecular level,
      several key regulators of the cell cycle have been identified: cyclin-dependent
      kinases and their cyclins stimulate the cell cycle progress and its arrest is
      determined by the activity of cdk inhibitors (Cip/Kip and INK protein families)
      and pocket protein family: Rb, p107 and p130. The biological activity of
      cyclin/cdk complexes allows the successive phases of the cell cycle to occur.
      Myoblast specialization, differentiation and fusion require the activity of
      myogenic regulatory factors, which include MyoD, myogenin, Myf5 and MRF4. MyoD
      and Myf5 play a role in muscle cell specialization, myogenin controls the
      differentiation process, whereas MRF4 is involved in myotube maturation. The
      deregulation of the cell cycle leads to uncontrolled proliferation, which
      antagonizes the functions of myogenic factors and it explains the lack of
      differentiation-specific gene expression in dividing cells. Conversely, the
      myogenic factor MyoD seems to cooperate with cell cycle inhibitors leading to
      inhibition of cell cycle progress and commitment to the differentiation process.
      The hypophosphorylated form of Rb and cdk inhibitors play an important role in
      permanent arrest of the cell cycle in differentiated myotubes. Furthermore,
      cyclin/cdk complexes not only regulate cell division by phosphorylation of
      several substrates, but may also control other cellular processes such as signal
      transduction, differentiation and apoptosis. Beyond regulating the cell cycle,
      Cip/Kip proteins play an important role in cell death, transcription regulation,
      cell fate determination, cell migration and cytoskeletal dynamics. The article
      summarizes current knowledge concerning the interactions of intracellular
      signaling pathways controlling crucial stages of fetal and regenerative
      myogenesis. 

PMID- 24864104
TI  - Synergistic interactions between anticancer chemotherapeutics and phenolic
      compounds and anticancer synergy between polyphenols.
AB  - Chemoprevention has recently gained a new dimension due to the possibility of
      studying the mechanisms of action of chemopreventive agents at the molecular
      level. Many compounds have been proved to inhibit early stages of carcinogenesis
      in experimental models. These compounds include both recognized drugs (such as
      tamoxifen and nonsteroidal anti-inflammatory drugs) and natural constituents of
      edible and therapeutic plants, particularly polyphenols. Phenolics are
      characterized by high structural diversity and, consequently, a very broad
      spectrum of biological activities. They are increasingly looked upon as a
      valuable alternative or a support for synthetic drugs, as evidenced by a growing
      number of clinical trials regarding the use of phenolic compounds and polyphenol
      rich extracts in chemoprevention and therapy. In the present work, we discuss the
      effectiveness of natural polyphenols as cancer preventive and therapeutic agents
      resulting from their synergy with synthetic or semisynthetic anticancer drugs as
      well as with other phenolic compounds of plant origin. 

PMID- 24864105
TI  - [Role of the RIG-I-like receptors in antiviral response].
AB  - The innate nonspecific immunity is the first line of defense against viral
      infection. Toll-like receptors (TLRs) and retinoic acid-inducible gene I (RIG-I)
      like receptors (RLRs) are two main receptor families detecting viral nucleic
      acid. So far, three RLR family members were characterized: RIG-I, MDA5 and LGP2.
      RLR constitute a family of cytoplasmic helicases, which recognized intracellular
      single-stranded and double-stranded RNA that is introduced to cytosol during
      viral infection and replication. In this work we review the current knowledge
      about the mechanisms of viral recognition by RIG-I-like receptors and their
      signaling pathways for the activation of type I interferons and pro-inflammatory
      cytokines synthesis. 

PMID- 24864106
TI  - [Heme metabolism as an integral part of iron homeostasis].
AB  - Heme, a ferrous iron protoporphyrin IX complex, is employed as a prosthetic group
      in a number of diverse heme proteins that participate in important cellular and
      systemic physiological processes. Provision of an adequate amount of iron for
      heme biosynthesis is one of the elemental hallmarks of intracellular iron
      homeostasis. In the cell the bioavailability of iron for the two main iron
      biological pathways--heme synthesis and the biogenesis of iron-sulfur clusters
      ([Fe-S])--is mainly regulated by the IRP/IRE posttranscriptional system. The
      biogenesis of [Fe-S] centers is crucial for heme synthesis because these co
      factors determine the activity of IRP1 and that of ferrochelatase, an enzyme
      responsible for the insertion of an iron into protoporphyrin IX to produce heme.
      On the other hand, delivery of iron for heme and hemoglobin synthesis in
      erythroblasts, precursors of erythrocytes in bone marrow, is an indispensable
      element of body iron homeostasis. This process relies on the recovery of iron
      from senescent red blood cells through the enzymatic degradation of heme
      molecules and recycling of iron to the circulation. Molecular coordination of
      these processes involves the activity of heme oxygenase 1, IRP1 and IRP2 as well
      as the functioning of the hepcidin-ferroportin regulatory axis. Recent studies
      show in mammals the existence of an expanded system of proteins involved in the
      transport of intact heme molecules at the cellular and systemic levels. The
      biological role of this system is of particular importance when the concentration
      of free heme reaches a toxic level in the body (intravascular hemolysis) as well
      as locally in cells having intensive heme metabolism such as erythroblasts and
      macrophages.

PMID- 24864107
TI  - [Curcumin in chemoprevention of breast cancer].
AB  - Breast cancer is the most common malignant cancer among women, both in Poland and
      worldwide. Due to the constantly increasing number of breast cancer cases, it is
      vital to develop effective activities in primary and secondary prevention. One of
      the promising methods of best value, connecting both types of cancer prevention,
      appears to be chemoprevention. Chemoprevention uses natural or synthetic
      compounds to inhibit, delay or reverse the process of carcinogenesis. Among
      ingredients of natural origin, great attention is paid to curcumin - a broad
      spectrum anti-cancer polyphenol derivative, extracted from the rhizome of Curcuma
      longa L. Curcumin has a number of chemopreventive properties such as anti
      inflammatory activity, induction of apoptosis, inhibition of angiogenesis as well
      as tumor metastasis. Numerous in vitro and in vivo studies have demonstrated the
      mentioned anti-cancer effect in the epithelial breast cell line MCF-10A and in
      the epithelial breast cell lines MCF-7, BT-474, SK-BR-3-hr and MDA-MB-231. The
      main problem associated with the use of curcumin as a chemopreventive agent in
      humans is its low absorption from the gastrointestinal tract, poor solubility in
      body fluids and low bioavailability. Current studies are underway to increase the
      bioavailability and effectiveness of curcumin in vivo. Good results in the
      prevention and the treatment of breast cancer could be ensured by curcumin
      nanoparticles coated with albumin, known as nanocurcumin. The studies using
      nanocurcumin, however, are still in the preclinical stage, which is why there is
      a need to conduct extensive long-term randomized clinical trials to determine its
      effectiveness. 

PMID- 24864108
TI  - [Hyperhomocysteinemia in patients with cardiovascular disease].
AB  - Homocysteine (Hcy) is an endogenous, non-structural protein, a sulfur-containing
      amino acid emerging on the pathway of methionine and cysteine, actively involved
      in numerous biochemical reactions. Total concentration of homocysteine in plasma
      of healthy humans is low and its level is between 5.0 and 15.0 mmol/l, assessed
      with the use of HPLC, or 5.0-12.0 mmol/l, using immunoassay methods. Higher
      concentration of this amino acid in blood is called hyperhomocysteinemia.
      Hyperhomocysteinemia is significantly correlated with cardiovascular disease and
      its complications: heart attacks and strokes. It is believed that
      hyperhomocysteinemia damages endothelial cells, reduces the flexibility of
      vessels, and adversely affects the process of hemostasis. In addition,
      hyperhomocysteinemia enhances the adverse effects of risk factors such as
      hypertension, smoking, and impaired glucose, lipid and lipoprotein metabolism, as
      well as promoting the development of inflammation. The concentration of
      homocysteine can be effectively lowered by supplementation with folic acid and
      vitamins B12 and B6. However, intervention studies conducted in the past decade
      did not confirm the clinical benefit of vitamin therapy lowering the level of
      homocysteine in blood of patients with cardiovascular disease. Moreover, there is
      not clear evidence from genetic studies that the presence of the gene for MTFHR
      polymorphism 677C>T, which is one of the most common causes of
      hyperhomocysteinemia, is also associated with the development of cardiovascular
      disease. These results led the researchers to discuss the role of homocysteine in
      the development and treatment of cardiovascular disease as well as the need for
      further research on this issue. 

PMID- 24864109
TI  - [Health-promoting properties of pectin].
AB  - Pectin, a heteropolysaccharide commercially derived from the cell wall of higher
      plants, is mainly used in food as a gelling agent in jams and jellies as well as
      a stabilizer in fruit juice and milk drinks. It has also received great interest
      as a source of dietary fiber. Furthermore, pectin is proved to have diverse
      biological activities including lipid and cholesterol level lowering effects,
      serum glucose and insulin content lowering effects, gastric emptying delay, and
      anti-cancer activities. Pectin and pectic oligosaccharides have been shown to
      induce apoptosis in human colonic adenocarcinoma cells and to have anti
      metastatic properties. Dietary pectin can bind metal ions, particularly lead
      ions, thus reducing their retention in the body and diminishing their toxic
      effects. On the other hand, pectin enhances intestinal solubility and absorption
      of ferric iron. Pectin with a low degree of esterification or having a large
      volume of linear oligogalacturonide segments shows significant mucoadhesion
      capacity in the gastrointestinal tract. In this way pectin forms a physical
      barrier protecting epithelium against opportunistic microbial invasion during
      stress. 

PMID- 24864110
TI  - IgE antibodies in toxoplasmosis.
AB  - Toxoplasmosis is a worldwide infection caused by the intracellular parasite
      Toxoplasma gondii. At least a third of the world human population is infected
      with the parasite, making it one of the most successful parasitic infections.
      Primary maternal infection may cause health-threatening sequelae for the fetus,
      or even cause death of the uterus. Reactivation of a latent infection in immune
      deficiency conditions such as AIDS and organ transplantation can cause fatal
      toxoplasmic encephalitis. Toxoplasmosis is a major cause of chorioretinitis,
      especially in individuals with impaired immune systems. In the acute phase,
      directly after invading the body, T. gondii begins to multiply rapidly. In the
      majority of cases acquired toxoplasmosis is asymptomatic. In the second week of
      infection, specific IgM antibodies are present in the blood. IgE antibodies
      appear at the same time, slightly preceding specific IgA antibodies. The
      concentration of IgE can be one of the parameters used for diagnosing an
      infection with T. gondii. Laboratory diagnosis, i.e. IgE and serologic assays,
      plays the main role in the diagnosis of congenital infection and assists in the
      confirmatory diagnosis of toxoplasmic encephalitis and ocular toxoplasmosis. This
      article is a review of IgE in toxoplasmosis. 

PMID- 24864111
TI  - [Animal models for the study of Helicobacter pylori infection].
AB  - The Gram-negative bacillus Helicobacter pylori is widely recognized as a major
      etiologic agent responsible for chronic active gastritis, peptic ulcers, the
      development of gastric cancer and mucosa-associated lymphoid tissue (MALT
      lymphoma). Still, little is known about the natural history of H. pylori
      infection, since patients usually after many years of not suffering from symptoms
      of the infection are simply asymptomatic. Since the research investigators
      carried out on human models has many limitations, there is an urgent need for the
      development of an animal model optimal and suitable for the monitoring of H.
      pylori infections. This review summarizes the recent findings on the suitability
      of animal models used in H. pylori research. Several animal models are useful for
      the assessment of pathological, microbiological and immunological consequences of
      infection, which makes it possible to monitor the natural history of H. pylori
      infection. Preclinical investigations on animal models are an essential stage of
      research which enrich the knowledge on treatment and prevention strategies.

PMID- 24864112
TI  - [Proteins in cancer multidrug resistance].
AB  - Multidrug Resistance (MDR) is defined as insensitivity to administered medicines
      that are structurally unrelated and have different molecular targets. Cancers
      possess numerous mechanisms of drug resistance, involving various aspects of cell
      biology. A pivotal role in this phenomenon is played by proteins--enzymatic or
      structural parts of the cell. Membrane transporters, including the main members
      of ABC protein family--P-gp, MRP1 and BCRP, as well as LRP, which builds
      structure of vaults, determine the multidrug-resistant phenotype by decreasing
      drug concentration within the cell or modifying its distribution to intracellular
      compartments. The pi isoform of protein enzyme--glutathione S-transferase (GSTP
      1), is responsible for excessive intensity of detoxification of cytostatics. A
      common example of altered drug target site that does not respond to chemotherapy
      is topoisomerase II alpha (TopoIIa). Alterations of programmed cell death result
      from expression of metallothionein (MT)--inhibitor of the process, and
      cytokeratin 18 (CK18), which, if in high concentration, also prevents apoptosis
      of cells. Several methods of decreasing activity of these proteins have been
      developed, aiming to overcome MDR in cancer cells. However, for a variety of
      reasons, their clinical suitability is still very low, leading to continuous
      increase in death rate among patients. This paper presents current state of
      knowledge on the most important examples of proteins responsible for MDR of
      cancer cells and molecular mechanisms of their action.

PMID- 24864113
TI  - [MSTN gene polymorphism in livestock animals].
AB  - Myostatin, also known as GDF8 (growth differentiation factor 8), belongs to one
      of the biggest groups of proteins, called transforming growth factors (TGF-beta).
      The protein regulates embryonic development and maintains homeostasis of full
      grown individuals. When the process of maturation is over, GDF8 becomes a
      negative regulator of skeletal muscle growth. The physiological role of myostatin
      is to prevent overgrowth of muscle tissue in various stages of organism
      development. It also inhibits the regeneration of skeletal muscles by weakening
      activation and proliferation of satellite cells and the migration of macrophages
      and myoblasts to the site of injury. Several mutations within the sequence of
      MSTN have been described; they may affect the activity of the protein in the
      tissues, and hence the level of the functional characteristics of the animals,
      which determine the value of breeding animals. Understanding the impact of
      individual mutations in the gene encoding the protein is particularly important
      in relation to production traits of livestock. 

PMID- 24864114
TI  - [Osteoarthritis: etiology, risk factors, molecular mechanisms].
AB  - Osteoarthritis is an incurable joint disease manifesting itself with gradually
      progressing degenerative changes, leading to premature motor disability. These
      changes mainly occur owing to an imbalance between the processes of degeneration
      and regeneration of articular cartilage structures. Until now many risk factors
      favoring the development of degenerative joint disease have been identified.
      These include age, weight, previously sustained traumas to joints, sports, sex
      and genetic predisposition. The latest scientific reports confirm that the
      pathogenesis of changes in osteoarthritic joints is complex and occurs on many
      levels. Enzymes belonging to the metalloproteinases family are mainly responsible
      for the degeneration of articular cartilage. Their activity is regulated by
      numerous pro-inflammatory cytokines, transcription factors and miRNA. A thorough
      analysis of all processes occurring in the afflicted joints needs to be carried
      out before effective therapeutic strategies can be developed.

PMID- 24864115
TI  - [Hereditary prostate cancer].
AB  - Prostate cancer (PC) is one of the most common cancers affecting men. It may soon
      become the main cancer--caused mortality among men all over the world. The
      genetic basis of prostate cancer is very complex and its etiology is poorly
      understood. The genes associated with hereditary predisposition to prostate
      cancer remain largely unknown. Family history of PC, particularly at a young age,
      is a strong risk factor. Through linkage analysis, numerous prostate cancer
      susceptibility chromosomal loci have been identified, including: HPC1 (1q24-25),
      PCaP (1q42.2-43), HPCX (Xq27-28), CAPB (1p36), HPC2 (17p12), HPC20 (20q13).
      However, it turned out that any of these genes is not a high-risk prostate cancer
      susceptibility gene. According to literature data HPC is associated with genes
      involved in androgen metabolism, including androgen receptor gene--AR, SRD5A2 and
      CYP17, genes involved in the DNA damage repair, including BRCA1, BRCA2, NBS1 and
      MLH1 or some developmental genes as HOXB13. Identification of PC high
      predisposition susceptibility genes is very important, because the ascertainment
      of a higher risk of prostate cancer development in mutation carriers enable to
      develop and implement in clinical practice suitable prophylactic programs which
      could prevent the disease or detect it in an early stage. It seems that better
      knowledge of the molecular pathology of prostate cancer could make it easier to
      discover new drugs of chemopreventive and chemotherapeutic activity. There are
      many cellular pathways associated with PC cancerogenesis, which may become a
      potential goal for such drugs in the future.

PMID- 24864116
TI  - Cost measurement of mental disorders in Germany.
AB  - BACKGROUND AND AIMS OF THE STUDY: Mental disorders are frequently investigated in
      economic evaluations. However, measuring direct costs of mental disorders is
      complex, in particular in Germany. We conducted a systematic review that
      investigated the following research questions: Which cost categories are
      assessed? Is the used data source (patient-reported data from interviews or
      questionnaires; claims data from health insurance; medical records from patient
      charts) associated with specific study characteristics? METHODS: We conducted a
      systematic literature search in PubMed. We included cost-of-illness studies
      (COIs) and cost-effectiveness analyses (CEAs) that measured patient level data on
      direct costs of mental disorders in Germany. RESULTS: We found 31 COIs and 17
      CEAs. Cost items could be assigned to the cost categories outpatient medical,
      outpatient non-medical, sheltered living, hospital, rehabilitation, nursing care,
      outpatient goods (medication and medical goods), other direct costs, and indirect
      costs. Most studies, in particular COIs and studies conducted from a societal
      perspective, used patient-reported data which suited to assess cost categories
      comprehensively. Studies based on claims data or medical records tended to
      include fewer cost categories. DISCUSSION: The sample size of 48 analyzed studies
      was rather small. However, our study investigated three methods to assess health
      care utilization -- using patient-reported data, claims data, or medical records 
      - and identified their respective strengths and weaknesses in the context of
      covered cost categories and further attributes. CONCLUSION: Studies measuring the
      direct costs of mental disorders in Germany mostly relied on patient-reported
      data to assess resource consumption. Although more objective, claims data were
      used less frequently and covered less cost categories. IMPLICATIONS FOR HEALTH
      POLICIES: The direct costs of mental disorders are likely to be underreported as
      relevant cost factors such as non-medical services or sheltered living were often
      neglected in the studies. Policy makers should consider this when deciding on
      measures that aim at reducing the costs of care. IMPLICATIONS FOR FURTHER
      RESEARCH: Eliciting data from patients seems to constitute an adequate instrument
      to assess a broad range of cost categories, even though this bears various
      methodological challenges. Further research should (i) ameliorate the methods of
      collecting data from patients in ensuring that all relevant costs are covered and
      that methodological flaws are minimised (ii) develop or improve methods for the
      combination of claims data from different data holders.

PMID- 24864117
TI  - A gap analysis for future supply of and demand for psychiatrists in Austria.
AB  - BACKGROUND: In the recent past, a rising caseload demonstrates increasing demand
      for psychiatrists, and ageing of the current mental health workforce will soon
      result in growing numbers of retirees. Under these conditions there is some
      concern whether we soon will face widening gaps in supply. AIMS OF THE STUDY:
      This study calculates projections of future use and supply of psychiatrists'
      services in Austria until 2030. Resulting gaps are calculated for different
      scenarios. DATA AND METHODS: We mostly use administrative data from several
      public authorities. To estimate the demand for services, we start from
      utilization data rather than medical need for services, as we do not have
      sufficient epidemiological information for Austria. We define several scenarios
      for the future development of use, all calculated separately for hospital and non
      hospital services. Future supply of psychiatric services is projected by applying
      activity levels to projected numbers of physicians, which are calculated using a
      stock and flow model. Outflows are modeled using assumptions derived from past
      activity patterns and current legislation on retirement. To model inflows, we
      need to gauge the impact of recent developments: Entrance barriers into medical
      education were introduced, Austria experienced a surge of medical students coming
      from Germany, and medical schools implemented quotas for different nationalities.
      Scenarios take several factors into account, like the shifting sex composition of
      the medical workforce, re-migration of foreign students, and the impact of
      entrance barriers on enrolment and drop-out rates. RESULTS: Depending on scenario
      assumptions, demand for psychiatrists will increase by 8% to 52%. But in all
      supply scenarios, supply will decline from 2016 onwards, thus widening gaps
      between supply and demand. Even in the most optimistic scenario, supply will have
      fallen below current levels by 2030. DISCUSSION: Compared to current rates of
      service use, a gap between supply and demand will start to widen soon. In the
      most optimistic combination of scenarios, demand will exceed supply from 2028
      onwards, and the projected gap will amount to about 5% of projected demand for
      services in 2030. LIMITATIONS: Gaps could be miscalculated due to lack of more
      detailed data, such as retirement patterns of psychiatrists. Shifting
      responsibilities between psychiatrists and other (mental) health workers as well
      as changes in psychiatrists' "productivity", e.g. due to more effective
      medications, were not modeled but would affect results. IMPLICATIONS FOR HEALTH
      POLICIES: It will be necessary to improve working and training conditions in
      order to avoid emigration and to attract a sufficient number of young entrants
      into the profession.

PMID- 24864118
TI  - Proximity to urban parks and mental health.
AB  - BACKGROUND: Urban parks have received attention in recent years as a possible
      environmental factor that could encourage physical activity, prevent obesity, and
      reduce the incidence of chronic conditions. Despite long hypothesized benefits of
      parks for mental health, few park studies incorporate mental health measures.
      AIMS OF THE STUDY: To test the association between proximity to urban parks and
      psychological distress. METHODS: Cross-sectional analysis of individual health
      survey responses. Data were collected for a study of capital improvements of
      neighborhood parks in Los Angeles. A survey was fielded on a sample of
      residential addresses, stratified by distance from the park (within 400m, 800m,
      1.6 km, and 3.2km; N=1070). We used multiple regression to estimate the
      relationship between the psychological distress as measured by the MHI-5 (outcome
      variable) and distance to parks (main explanatory variable), controlling for
      observed individual characteristics. RESULTS: Mental health is significantly
      related to residential distance from parks, with the highest MHI-5 scores among
      residents within short walking distance from the park (400m) and decreasing
      significantly over the next distances. The number of visits and physical activity
      minutes are significantly and independently related to distance, although
      controlling for them does not reduce the association between distance and mental
      health. DISCUSSION AND LIMITATIONS: This paper provides a new data point for an
      arguably very old question, but for which empirical data are sparse for the US. A
      nearby urban park is associated with the same mental health benefits as
      decreasing local unemployment rates by 2 percentage points, suggesting at least
      the potential of environmental interventions to improve mental health. The
      analysis is cross-sectional, making it impossible to control for important
      confounders, including residential selection. IMPLICATIONS FOR HEALTH POLICY:
      Mental health policy has traditionally focused on individual-centered
      interventions. Just as health policy for preventable chronic illnesses has
      shifted attention to modifiable environmental determinants, population mental
      health may benefit substantially from environmental interventions. IMPLICATIONS
      FOR FUTURE RESEARCH: Policy evaluations should incorporate mental health measures
      when assessing neighborhood improvement programs and physical environments. Many
      recent and ongoing studies have excluded mental health measure in the belief that
      they are too burdensome for respondents or irrelevant. If a causal relationship
      is confirmed, then ameliorating neighborhood conditions and physical environments
      could represent a scalable way to improve mental health issues for large
      populations.

PMID- 24864119
TI  - Health insurance in China: variation in co-payments and psychiatric hospital
      utilization.
AB  - BACKGROUND: Economic reform in China 30 years ago virtually eliminated all public
      health insurance. In the last 10 years, diverse government insurance programs
      have been implemented, now covering 95% of the population, primarily for
      inpatient care. While the development of health care in China is an incomplete
      work in progress and highly variable, it is unclear whether the depth of
      insurance coverage affects the accessibility, length of stay (LOS) of inpatient
      mental health services or not. AIM OF THE STUDY: This study aims to examine the
      relationship between variation in insurance coverage, accessibility to inpatient
      mental health care and intensity of care as measured by length of stay (LOS).
      METHODS: Using administrative data from the Guangzhou Psychiatric Hospital (GPH),
      we used regression models to determine the relationship between the depth of
      insurance coverage and the likelihood of hospital utilization and LOS net of
      sociodemographic characteristics and diagnosis. RESULTS: Between April 1, 2010
      and March 31, 2013, 8,478 patients were discharged with ICD-10 psychiatric
      diagnoses with an average LOS of 75.1 (sd=244.3) days, among which 4,727 (55.8%)
      patients were first admissions. Logistic regression analysis showed that
      insurance plans with lower co-payments were significant predictors of multiple
      psychiatric admissions and longer LOS. IMPLICATIONS FOR HEALTH POLICY: These data
      point to significant variability in the health insurance coverage in China and
      indicate a clear need for greater equalization in future years. Although the
      Chinese government has provided at least shallow coverage to virtually all of its
      citizens at this stage, further efforts are needed to expand and equalize
      coverage as economic development proceeds, especially in rural areas.
      IMPLICATIONS FOR FURTHER RESEARCH: Although variation in health insurance plans
      in China are extensive and impact the accessibility and duration of psychiatric
      hospital care, their impact on outcomes and use of post-discharge outpatient care
      is unknown and requires further study.

PMID- 24864120
TI  - Characterization of atrial septal defect by simultaneous multiplane two
      dimensional echocardiography.
AB  - AIMS: The aim of this study was to assess the value of two-dimensional (2D)
      transthoracic simultaneous multiplane imaging (SMPI) in the evaluation of
      suitability for percutaneous atrial septal secundum defect (ASD) closure compared
      with the golden standard 2D transoesophageal echocardiography (TEE). METHODS AND
      RESULTS: Twenty-nine patients with an ASD underwent both SMPI and TEE. Ten
      patients (34%) were male (age 41 +/- 18 years, range 20-74). SMPI assessment of
      ASD size and rims included xPlane and I-rotate modes. Rims were defined as
      suitable for ASD percutaneous closure using a cut-off value of 5 mm. There were
      no significant differences between SMPI in xPlane mode and TEE regarding the
      sizes of the anterior-posterior dimension (13.7 +/- 4.5 vs. 14.5 +/- 5.2 mm) and
      superior-inferior dimension (13.5 +/- 3.9 vs. 14.1 +/- 5.0 mm, respectively).
      Agreement for the aortic, atrioventricular, inferior, right upper pulmonary vein,
      and superior rims was 100, 100, 100, 96, and 96%, respectively. CONCLUSION: The
      SMPI technique can reliably assess the dimensions and rim size of a secundum ASD
      for pre-interventional selection when compared with TEE and has thus the
      potential to replace TEE.

PMID- 24864122
TI  - Nasopharyngeal wash versus swab specimens for culture of nontypeable Haemophilus
      influenzae and other respiratory bacterial pathogens.

PMID- 24864121
TI  - A broadly neutralizing human monoclonal antibody exhibits in vivo efficacy
      against both human metapneumovirus and respiratory syncytial virus.
AB  - BACKGROUND: Human metapneumovirus (HMPV) is a leading cause of acute respiratory
      tract infection, with significant morbidity and mortality. No licensed vaccines
      or therapeutic agents exist. Monoclonal antibodies (mAbs) are effective at
      preventing other infectious diseases and could be used against HMPV in high-risk
      hosts. METHODS: In vitro assays were performed to assess the neutralizing
      activity and affinity kinetics of human mAb 54G10. A new mouse model was
      developed to assess prophylactic and therapeutic efficacy in vivo. The epitope of
      54G10 was identified by generating mAb-resistant mutants (MARMs). RESULTS: At low
      concentrations, 54G10 neutralized all 4 subgroups of HMPV in vitro and had
      subnanomolar affinity for the fusion protein. DBA/2 mice were permissive for all
      4 HMPV subgroups, and 54G10 was effective both prophylactically and
      therapeutically against HMPV in vivo. Sequencing of HMPV MARMs identified the
      54G10 epitope, which was similar to an antigenic site on respiratory syncytial
      virus (RSV). 54G10 also exhibited in vitro neutralizing activity and in vivo
      protective and therapeutic efficacy against RSV. CONCLUSIONS: Human mAb 54G10 has
      broad neutralizing activity against HMPV and could have prophylactic and
      therapeutic utility clinically. The conserved epitope could represent a
      structural vaccine target for HMPV and RSV.

PMID- 24864126
TI  - Factors affecting enrollment in a randomized controlled trial for Japanese
      metastatic breast cancer patients (SELECT BC-FEEL)--a prospective study.
AB  - To accelerate the completion of clinical trials, it is critical to obtain, at
      high rates, informed consent to participate from patients who are eligible. It is
      therefore important to know what factors affect the participation rates of
      eligible patients. Selection of effective chemotherapy for breast cancer and its
      successor selection of effective chemotherapy for breast cancer-CONFIRM are
      randomized controlled trials conducted for Japanese patients with chemotherapy
      naive metastatic breast cancer. These trials are intended to compare the current
      standard chemotherapeutic regimens in the first-line setting, which are taxanes
      for selection of effective chemotherapy for breast cancer and anthracyclines for
      selection of effective chemotherapy for breast cancer-CONFIRM, respectively, and
      an oral regimen of TS-1 in terms of overall survival. We are conducting
      prospective studies to identify the factors affecting the rates at which informed
      consent is obtained in selection of effective chemotherapy for breast cancer and
      breast cancer-CONFIRM. We are using a self-administered questionnaire that we
      have developed to collect information regarding patients' characteristics and
      attitude to clinical trials. 

PMID- 24864123
TI  - Sevelamer does not decrease lipopolysaccharide or soluble CD14 levels but
      decreases soluble tissue factor, low-density lipoprotein (LDL) cholesterol, and
      oxidized LDL cholesterol levels in individuals with untreated HIV infection.
AB  - Abnormal levels of inflammation are associated with cardiovascular disease and
      mortality in human immunodeficiency virus (HIV)-infected patients. Microbial
      translocation, which may cause inflammation, is decreased by sevelamer in
      patients undergoing hemodialysis. In this single-arm study, we evaluated the
      effects of 8 weeks of sevelamer therapy on 36 HIV-infected subjects who were not
      receiving antiretroviral therapy. Sevelamer did not significantly change markers
      of microbial translocation, inflammation, or T-cell activation. During sevelamer
      treatment, however, levels of soluble tissue factor, low-density lipoprotein
      (LDL) cholesterol, and oxidized LDL cholesterol decreased significantly, whereas
      D-dimer levels increased. Thus, in this study population, sevelamer did not
      reduce microbial translocation but may have yielded cardiovascular benefits.
      CLINICAL TRIALS REGISTRATION: NCT 01543958.

PMID- 24864124
TI  - Small molecule targeting malaria merozoite surface protein-1 (MSP-1) prevents
      host invasion of divergent plasmodial species.
AB  - Malaria causes nearly 1 million deaths annually. Recent emergence of multidrug
      resistance highlights the need to develop novel therapeutic interventions against
      human malaria. Given the involvement of sugar binding plasmodial proteins in host
      invasion, we set out to identify such proteins as targets of small glycans.
      Combining multidisciplinary approaches, we report the discovery of a small
      molecule inhibitor, NIC, capable of inhibiting host invasion through interacting
      with a major invasion-related protein, merozoite surface protein-1 (MSP-1). This
      interaction was validated through computational, biochemical, and biophysical
      tools. Importantly, treatment with NIC prevented host invasion by Plasmodium
      falciparum and Plasmodium vivax--major causative organisms of human malaria. MSP
      1, an indispensable antigen critical for invasion and suitably localized in
      abundance on the merozoite surface represents an ideal target for antimalarial
      development. The ability to target merozoite invasion proteins with specific
      small inhibitors opens up a new avenue to target this important pathogen.

PMID- 24864125
TI  - Responses to A(H1N1)pdm09 influenza vaccines in participants previously
      vaccinated with seasonal influenza vaccine: a randomized, observer-blind,
      controlled study.
AB  - BACKGROUND: Prior receipt of a trivalent seasonal influenza vaccine (TIV) can
      affect hemagglutination inhibition (HI) antibody responses to pandemic influenza
      vaccines. We investigated the effect of TIV priming on humoral responses to AS03
      adjuvanted and nonadjuvanted A(H1N1)pdm09 vaccines, the role of AS03 on cell
      mediated immune (CMI) responses, and vaccine safety. METHODS: Healthy adults
      (aged 19-40 years) were randomized 1:1:1:1 to receive TIV or saline followed 4
      months later by 2 doses, 3 weeks apart, of adjuvanted or nonadjuvanted
      A(H1N1)pdm09 vaccine and followed up to study end (day 507). Pre- and
      postvaccination responses of HI and neutralizing antibody, CD4(+)/CD8(+) T cells,
      memory B cells, and plasmablasts were assessed. RESULTS: Ninety-nine of the 133
      participants enrolled completed the study. No vaccine-related serious adverse
      events were recorded. In TIV-primed participants, A(H1N1)pdm09-specific antibody
      and CD4(+) T-cell and memory B-cell responses to the pandemic vaccine tended to
      be diminished. Vaccine adjuvantation led to increased responses of vaccine
      homologous and -heterologous HI and neutralizing antibodies and CD4(+) T cells,
      homologous memory B cells, and plasmablasts. CONCLUSIONS: In healthy adults,
      prior TIV administration decreased humoral and CMI responses to A(H1N1)pdm09
      vaccine. Adjuvantation of A(H1N1)pdm09 antigen helped to overcome immune
      interference between the influenza vaccines. No safety concerns were observed.
      REGISTRATION: Clinical Trials.gov identifier NCT00707967.

PMID- 24864128
TI  - On the fluid dynamics of a laboratory scale single-use stirred bioreactor.
AB  - The commercial success of mammalian cell-derived recombinant proteins has
      fostered an increase in demand for novel single-use bioreactor (SUB) systems that
      facilitate greater productivity, increased flexibility and reduced costs (Zhang
      et al., 2010). These systems exhibit fluid flow regimes unlike those encountered
      in traditional glass/stainless steel bioreactors because of the way in which they
      are designed. With such disparate hydrodynamic environments between SUBs
      currently on the market, traditional scale-up approaches applied to stirred tanks
      should be revised. One such SUB is the Mobius(r) 3 L CellReady, which consists of
      an upward-pumping marine scoping impeller. This work represents the first
      experimental study of the flow within the CellReady using a Particle Image
      Velocimetry (PIV) approach, combined with a biological study into the impact of
      these fluid dynamic characteristics on cell culture performance. The PIV study
      was conducted within the actual vessel, rather than using a purpose-built mimic.
      PIV measurements conveyed a degree of fluid compartmentalisation resulting from
      the up-pumping impeller. Both impeller tip speed and fluid working volume had an
      impact upon the fluid velocities and spatial distribution of turbulence within
      the vessel. Cell cultures were conducted using the GS-CHO cell-line (Lonza)
      producing an IgG4 antibody. Disparity in cellular growth and viability throughout
      the range of operating conditions used (80-350 rpm and 1-2.4 L working volume)
      was not substantial, although a significant reduction in recombinant protein
      productivity was found at 350 rpm and 1 L working volume (corresponding to the
      highest Reynolds number tested in this work). The study shows promise in the use
      of PIV to improve understanding of the hydrodynamic environment within individual
      SUBs and allows identification of the critical hydrodynamic parameters under the
      different flow regimes for compatibility and scalability across the range of
      bioreactor platforms.

PMID- 24864127
TI  - The number of Neisseria meningitidis type IV pili determines host cell
      interaction.
AB  - As mediators of adhesion, autoaggregation and bacteria-induced plasma membrane
      reorganization, type IV pili are at the heart of Neisseria meningitidis
      infection. Previous studies have proposed that two minor pilins, PilV and PilX,
      are displayed along the pilus structure and play a direct role in mediating these
      effects. In contrast with this hypothesis, combining imaging and biochemical
      approaches we found that PilV and PilX are located in the bacterial periplasm
      rather than along pilus fibers. Furthermore, preventing exit of these proteins
      from the periplasm by fusing them to the mCherry protein did not alter their
      function. Deletion of the pilV and pilX genes led to a decrease in the number,
      but not length, of pili displayed on the bacterial surface indicating a role in
      the initiation of pilus biogenesis. By finely regulating the expression of a
      central component of the piliation machinery, we show that the modest reductions
      in the number of pili are sufficient to recapitulate the phenotypes of the pilV
      and pilX mutants. We further show that specific type IV pili-dependent functions
      require different ranges of pili numbers. 

PMID- 24864129
TI  - TRIM29 as a novel biomarker in pancreatic adenocarcinoma.
AB  - BACKGROUND AND AIM: Tripartite motif-containing 29 (TRIM29) is structurally a
      member of the tripartite motif family of proteins and is involved in diverse
      human cancers. However, its role in pancreatic cancer remains unclear. METHODS:
      The expression pattern of TRIM29 in pancreatic ductal adenocarcinoma was assessed
      by immunocytochemistry. Multivariate logistic regression analysis was used to
      investigate the association between TRIM29 and clinical characteristics. In vitro
      analyses by scratch wound healing assay and invasion assays were performed using
      the pancreatic cancer cell lines. RESULTS: Immunohistochemical analysis showed
      TRIM29 expression in pancreatic cancer tissues was significantly higher  (n =
      186) than that in matched adjacent nontumor tissues. TRIM29 protein expression
      was significantly correlated with lymph node metastasis (P = 0.019). Patients
      with positive TRIM29 expression showed both shorter overall survival and shorter
      recurrence-free survival than those with negative TRIM29 expression. Multivariate
      analysis revealed that TRIM29 was an independent factor for pancreatic cancer
      over survival (HR = 2.180, 95% CI: 1.324-4.198, P = 0.011). In vitro, TRIM29
      knockdown resulted in inhibition of pancreatic cancer cell proliferation,
      migration, and invasion. CONCLUSIONS: Our results indicate that TRIM29 promotes
      tumor progression and may be a novel prognostic marker for pancreatic ductal
      adenocarcinoma.

PMID- 24864130
TI  - The clinical significance of PR, ER, NF- kappa B, and TNF- alpha in breast
      cancer.
AB  - OBJECTIVES: To investigate the expression of estrogen (ER), progesterone
      receptors (PR), nuclear factor- kappa B (NF- kappa B), and tumor necrosis factor-
      alpha (TNF- alpha ) in human breast cancer (BC), and the correlation of these
      four parameters with clinicopathological features of BC. METHODS AND RESULTS: We
      performed an immunohistochemical SABC method for the identification of ER, PR, NF
      kappa B, and TNF- alpha expression in 112 patients with primary BC. The total
      positive expression rate of ER, PR, NF- kappa B, and TNF- alpha was 67%, 76%,
      84%, and 94%, respectively. The expressions of ER and PR were correlated with
      tumor grade, TNM stage, and lymph node metastasis (P < 0.01, resp.), but not with
      age, tumor size, histological subtype, age at menarche, menopause status, number
      of pregnancies, number of deliveries, and family history of cancer. Expressions
      of ER and PR were both correlated with NF- kappa B and TNF- alpha expression (P <
      0.05, resp.). Moreover, there was significant correlation between ER and PR (P <
      0.0001) as well as between NF- kappa B and TNF- alpha expression (P < 0.05).
      CONCLUSION: PR and ER are highly expressed, with significant correlation with NF-
      kappa B and TNF- alpha expression in breast cancer. The important roles of ER and
      PR in invasion and metastasis of breast cancer are probably associated with NF-
      kappa B and TNF- alpha expression.

PMID- 24864131
TI  - Evaluation of oxidative stress biomarkers in patients with fixed orthodontic
      appliances.
AB  - AIM: The aim of this study was to examine the changes in the levels of
      interleukine-1 beta (IL-1 beta ), tumor necrosis factor alpha (TNF- alpha ),
      malondialdehyde (MDA), nitric oxide (NO), and 8-hydroxydeoxyguanosine (8-OHdG) in
      saliva and IL-1 beta , TNF- alpha , and NO in gingival crevicular fluid (GCF)
      samples of patients with fixed orthodontic appliances. MATERIAL AND METHOD: The
      subject population consisted of 50 volunteers who were in need of orthodontic
      treatment with fixed orthodontic appliances. GCF and saliva samples were obtained
      from all individuals before treatment, at 1st month of treatment and at 6th month
      of treatment. Periodontal clinical parameters were measured. Samples were
      investigated to detect IL-1 beta , TNF- alpha , and 8-OHdG levels using ELISA
      method and NO and MDA levels using spectrophotometric method. RESULTS: Since IL-1
      beta level detected in GCF at the 6th month of orthodontic treatment is
      statistically significant according to baseline (P < 0.05), all other biochemical
      parameters detected both in saliva and in GCF did not show any significant change
      at any measurement periods. CONCLUSION: Orthodontic tooth movement and
      orthodontic materials used in orthodontic treatment do not lead to a change above
      the physiological limits that is suggestive of oxidative damage in both GCF and
      saliva.

PMID- 24864132
TI  - Chemokine CXCL16 expression suppresses migration and invasiveness and induces
      apoptosis in breast cancer cells.
AB  - BACKGROUND: Increasing evidence argues that soluble CXCL16 promotes
      proliferation, migration, and invasion of cancer cells in vitro. However, the
      role of transmembrane or cellular CXCL16 in cancer remains relatively unknown. In
      this study, we determine the function of cellular CXCL16 as tumor suppressor in
      breast cancer cells. METHODS: Expression of cellular CXCL16 in breast cancer cell
      lines was determined at both RNA and protein levels. In vitro and in vivo studies
      that overexpressed or downregulated CXCL16 were conducted in breast cancer cells.
      RESULTS: We report differential expression of cellular CXCL16 in breast cancer
      cell lines that was negatively correlated with cell invasiveness and migration.
      Overexpression of CXCL16 in MDA-MB-231 cells led to a decrease in cell invasion
      and migration and induced apoptosis of the cells; downregulation of CXCL16 in MCF
      7 cells increased cell migration and invasiveness. Consistent with the in vitro
      data, CXCL16 overexpression inhibited tumorigenesis in vivo. CONCLUSIONS:
      Cellular CXCL16 suppresses invasion and metastasis of breast cancer cells in
      vitro and inhibits tumorigenesis in vivo. Targeting of cellular CXCL16 expression
      is a potential therapeutic strategy for breast cancer.

PMID- 24864133
TI  - Differential associations of inflammatory and endothelial biomarkers with disease
      activity in rheumatoid arthritis of short duration.
AB  - OBJECTIVES: To estimate endothelial dysfunction in patients with rheumatoid
      arthritis (RA) of short duration in relation to disease activity based on the
      assessment of 28 joints (DAS28). METHODS: We studied 29 patients (22 women, mean
      age 41 (SD, 9) years) with RA of short duration and 29 healthy controls. The RA
      subjects were divided into those with low (DAS28: 2.6-5.1, n = 18) or high (DAS28
      > 5.1, n = 11) disease activity. Exclusion criteria included clinically overt
      atherosclerosis and other coexistent diseases. Biochemical markers of
      inflammatory activation and endothelial dysfunction were measured. RESULTS: There
      were no significant intergroup differences in the majority of classical
      cardiovascular risk factors. High-sensitivity C-reactive protein, tumor necrosis
      factor- alpha , and interleukin-6 were increased in RA subjects. Compared to the
      controls, levels of soluble vascular cell adhesion molecule-1, von Willebrand
      factor, and pentraxin-3 were significantly elevated in RA subjects with low
      disease activity, exhibiting no further significant rises in those with high
      disease activity. Asymmetric dimethyl-L-arginine, soluble E-selectin, monocyte
      chemotactic protein-1, and osteoprotegerin were increased only in RA patients
      with high disease activity. CONCLUSIONS: Our findings might suggest a
      dissociation of pathways governing generalized and joint-specific inflammatory
      reactions from those involved in endothelial activation and inflammation within
      the vascular wall.

PMID- 24864134
TI  - Activation of adenosine A3 receptor alleviates TNF-alpha-induced inflammation
      through inhibition of the NF-kappaB signaling pathway in human colonic epithelial
      cells.
AB  - To investigate the expression of adenosine A3 receptor (A3AR) in human colonic
      epithelial cells and the effects of A3AR activation on tumor necrosis factor
      alpha (TNF-alpha-) induced inflammation in order to determine its mechanism of
      action in human colonic epithelial cells, human colonic epithelial cells (HT-29
      cells) were treated with different concentrations of 2-Cl-IB-MECA prior to TNF
      alpha stimulation, followed by analysis of NF-kappaB signaling pathway activation
      and downstream IL-8 and IL-1beta production. A3AR mRNA and protein were expressed
      in HT-29 cells and not altered by changes in TNF-alpha or 2-Cl-IB-MECA.
      Pretreatment with 2-Cl-IB-MECA prior to stimulation with TNF-alpha attenuated NF
      kappaB p65 nuclear translocation as p65 protein decreased in the nucleus of cells
      and increased in the cytoplasm, inhibited the degradation of IkappaB-alpha, and
      reduced phosphorylated-IkappaB-alpha level significantly, compared to TNF-alpha
      only-treated groups. Furthermore, 2-Cl-IB-MECA significantly decreased TNF-alpha
      stimulated IL-8 and IL-1beta mRNA expression and secretion, compared to the TNF
      alpha-only treated group. These results confirm that A3AR is expressed in human
      colonic epithelial cells and demonstrate that its activation has an anti
      inflammatory effect, through the inhibition of NF-kappaB signaling pathway, which
      leads to inhibition of downstream IL-8 and IL-1beta expression. Therefore, A3AR
      activation may be a potential treatment for gut inflammatory diseases such as
      inflammatory bowel disease.

PMID- 24864136
TI  - Incidence and survival analysis of gastrointestinal stromal tumors in shanghai: a
      population-based study from 2001 to 2010.
AB  - Objectives. A population-based study was undertaken to investigate the
      epidemiological features of gastrointestinal stromal tumors (GISTs) in Shanghai,
      especially the incidence and the preliminary exploration of survival. Methods. A
      total of 1923 patients with GISTs diagnosed from 2001 to 2010 in Shanghai were
      reviewed. The annual incidence and overall survival of GISTs were calculated; Cox
      proportional hazards' regression was used to analyze several prognostic factors.
      Results. The average crude incidence of GISTs was 2.11 per 100,000 between 2004
      and 2008, and the age-standardized incidence was 1.28 per 100,000. The incidence
      increased gradually from 2004 to 2008. In addition, 57% of cases had GIST in the
      stomach and 33% in the intestine. The 5-year overall survival of GISTs was
      86.98%. The Cox regression analysis showed older age (>=65 yr versus <40 yr, HR =
      5.085; (40, 65) yr versus <40 yr, HR = 1.975), male gender (HR = 1.474), and
      tumor locations (intestinal versus stomach, HR = 1.609) were predictors of its
      mortality. Conclusion. GISTs, mainly occurring in the stomach, are more common in
      elderly population, with an increasing incidence from 2004 to 2008. Older age,
      male gender, and tumor locations are risk factors for its mortality. 

PMID- 24864137
TI  - Susceptibility of Porphyromonas gingivalis and Streptococcus mutans to
      Antibacterial Effect from Mammea americana.
AB  - The development of periodontal disease and dental caries is influenced by several
      factors, such as microorganisms of bacterial biofilm or commensal bacteria in the
      mouth. These microorganisms trigger inflammatory and immune responses in the
      host. Currently, medicinal plants are treatment options for these oral diseases.
      Mammea americana extracts have reported antimicrobial effects against several
      microorganisms. Nevertheless, this effect is unknown against oral bacteria.
      Therefore, the aim of this study was to evaluate the antibacterial effect of M.
      americana extract against Porphyromonas gingivalis and Streptococcus mutans. For
      this, an experimental study was conducted. Ethanolic extract was obtained from
      seeds of M. americana (one oil phase and one ethanolic phase). The strains of
      Porphyromonas gingivalis ATCC 33277 and Streptococcus mutans ATCC 25175 were
      exposed to this extract to evaluate its antibacterial effect. Antibacterial
      activity was observed with the two phases of M. americana extract on P.
      gingivalis and S. mutans with lower MICs (minimum inhibitory concentration).
      Also, bactericidal and bacteriostatic activity was detected against S. mutans,
      depending on the concentration of the extract, while on M. americana extract
      presented only bacteriostatic activity against P. gingivalis. These findings
      provide important and promising information allowing for further exploration in
      the future. 

PMID- 24864138
TI  - Simple and Robust Analysis of Cefuroxime in Human Plasma by LC-MS/MS: Application
      to a Bioequivalence Study.
AB  - A simple, robust LC-MS/MS assay for quantifying cefuroxime in human plasma was
      developed. Cefuroxime and tazobactam, as internal standard (IS), were extracted
      from human plasma by methanol to precipitate protein. Separation was achieved on
      a Zorbax SB-Aq (4.6 * 250 mm, 5  MU m) column under isocratic conditions. The
      calibration curve was linear in the concentration range of 0.0525-21.0  MU g/mL
      (r = 0.9998). The accuracy was higher than 90.92%, while the intra- and interday
      precision were less than 6.26%. The extraction procedure provides recovery ranged
      from 89.44% to 92.32%, for both analyte and IS. Finally, the method was
      successfully applied to a bioequivalence study of a single 500 mg dose of
      cefuroxime axetil in 22 healthy Chinese male subjects under fasting condition.
      Bioequivalence was determined by calculating 90% Cls for the ratios of C max,
      AUC0-t , and AUC0-infinity values for the test and reference products, using
      logarithmic transformed data. The 90% Cls for the ratios of C max (91.4%~104.2%),
      AUC0-t (97.4%~110.9%), and AUC0-infinity (97.6%~111.1%) values were within the
      predetermined range. It was concluded that the two formulations (test for
      capsule, reference for tablet) analyzed were bioequivalent in terms of rate and
      extent of absorption and the method met the principle of quick and easy clinical
      analysis. 

PMID- 24864139
TI  - Long-term ultrasound follow-up of thyroid colloid cysts.
AB  - Objective. This study aimed to assess the interval changes of thyroid colloid
      cysts (TCCs) by performing long-term ultrasound (US) follow-up examinations.
      Methods. From 2007 to 2008, 437 patients underwent a lobectomy for the treatment
      of papillary thyroid microcarcinoma. Among them, 268 patients underwent 4 or more
      postoperative US follow-ups after surgery. This study investigated the prevalence
      and interval changes of TCCs >=3 mm by using US follow-ups. Results. Among 268
      patients, 35 (13.1%) had TCCs >=3 mm by a preoperative thyroid US, and 6 (2.2%)
      had newly detected TCCs at a US follow-up. Through long-term US follow-up, the
      interval changes for TCCs were classified as follows: no interval change (n = 8),
      gradual increase (n = 8), gradual decrease (n = 5), positive fluctuation (n = 3),
      negative fluctuation (n = 6), disappearance (n = 5), and new detection (n = 6).
      None of the TCC cases had a TCC that was >=10 mm at its largest diameter, and no
      patient complained of any relevant symptoms pertaining to the TCCs. Conclusions.
      In this study, TCCs demonstrated various interval changes, but no abrupt increase
      was found or acute onset of symptoms occurred. 

PMID- 24864140
TI  - Stability of miR-126 in Urine and Its Potential as a Biomarker for Renal
      Endothelial Injury with Diabetic Nephropathy.
AB  - Background. The purpose of the present study was to assess the feasibility of
      using miR-126 in the urine as a biomarker for diabetic nephropathy. Methods.
      miRNAs were extracted from the urine samples of T2DM patients with diabetic
      nephropathy (DN; n = 92), T2DM without DN (n = 86), and 85 healthy volunteers
      using quantitative reverse transcriptase polymerase chain reaction (real-time
      polymerase chain reaction) analysis. Stability of urinary miR-126 and factors
      that affected the stability were assessed. A subgroup analysis was also carried
      out to compare the urinary miR-126 level in T2DM patients well controlled by the
      treatment versus those who were not well controlled. Results. Urinary miR-126 was
      stable when the urine samples were kept at room temperature for extended period
      of time, 4 degrees C, -20 degrees C, and -80 degrees C for up to 12 hours or
      subjected to 10 freeze-and-thaw cycle. Urinary miR-126 was significantly higher
      in T2DM patients with DN (5.76 +/- 0.33 versus 3.25 +/- 0.45 in T2DM patients
      without DN). Successful treatment significantly reduced urinary miR-126 in T2DM
      patients with DN to 3.89 +/- 0.52 (P < 0.05). Conclusion. miR-126 in the urine is
      stable and it could be used as a biomarker of DN and to monitor the treatment
      response. 

PMID- 24864135
TI  - Evidence-based recommendations for natural bodybuilding contest preparation:
      nutrition and supplementation.
AB  - The popularity of natural bodybuilding is increasing; however, evidence-based
      recommendations for it are lacking. This paper reviewed the scientific literature
      relevant to competition preparation on nutrition and supplementation, resulting
      in the following recommendations. Caloric intake should be set at a level that
      results in bodyweight losses of approximately 0.5 to 1%/wk to maximize muscle
      retention. Within this caloric intake, most but not all bodybuilders will respond
      best to consuming 2.3-3.1 g/kg of lean body mass per day of protein, 15-30% of
      calories from fat, and the reminder of calories from carbohydrate. Eating three
      to six meals per day with a meal containing 0.4-0.5 g/kg bodyweight of protein
      prior and subsequent to resistance training likely maximizes any theoretical
      benefits of nutrient timing and frequency. However, alterations in nutrient
      timing and frequency appear to have little effect on fat loss or lean mass
      retention. Among popular supplements, creatine monohydrate, caffeine and beta
      alanine appear to have beneficial effects relevant to contest preparation,
      however others do not or warrant further study. The practice of dehydration and
      electrolyte manipulation in the final days and hours prior to competition can be
      dangerous, and may not improve appearance. Increasing carbohydrate intake at the
      end of preparation has a theoretical rationale to improve appearance, however it
      is understudied. Thus, if carbohydrate loading is pursued it should be practiced
      prior to competition and its benefit assessed individually. Finally, competitors
      should be aware of the increased risk of developing eating and body image
      disorders in aesthetic sport and therefore should have access to the appropriate
      mental health professionals. 

PMID- 24864141
TI  - Bone and mineral metabolism in patients with primary aldosteronism.
AB  - Primary aldosteronism represents major cause of secondary hypertension, strongly
      associated with high cardiovascular morbidity and mortality. Aldosterone excess
      may influence mineral homeostasis, through higher urinary calcium excretion
      inducing secondary increase of parathyroid hormone. Recently, in a cohort of PA
      patients a significant increase of primary hyperparathyroidism was found,
      suggesting a bidirectional functional link between the adrenal and parathyroid
      glands. The aim of this study was to evaluate the impact of aldosterone excess on
      mineral metabolism and bone mass density. In 73 PA patients we evaluated
      anthropometric and biochemical parameters, renin-angiotensin-aldosterone system,
      calcium-phosphorus metabolism, and bone mineral density; control groups were 73
      essential hypertension (EH) subjects and 40 healthy subjects. Compared to HS and
      EH, PA subjects had significantly lower serum calcium levels and higher urinary
      calcium excretion. Moreover, PA patients showed higher plasma PTH, lower serum
      25(OH)-vitamin D levels, higher prevalence of vitamin D deficiency (65% versus
      25% and 25%; P < 0.001), and higher prevalence of osteopenia/osteoporosis (38.5
      and 10.5%) than EH (28% and 4%) and NS (25% and 5%), respectively. This study
      supports the hypothesis that bone loss and fracture risk in PA patients are
      potentially the result of aldosterone mediated hypercalciuria and the consecutive
      secondary hyperparathyroidism. 

PMID- 24864142
TI  - Association of irisin with fat mass, resting energy expenditure, and daily
      activity in conditions of extreme body mass index.
AB  - FNDC5/irisin has been recently postulated as beneficial in the treatment of
      obesity and diabetes because it is induced in muscle by exercise, increasing
      energy expenditure. However, recent reports have shown that WAT also secretes
      irisin and that circulating irisin is elevated in obese subjects. The aim of this
      study was to evaluate irisin levels in conditions of extreme BMI and its
      correlation with basal metabolism and daily activity. The study involved 145
      female patients, including 96 with extreme BMIs (30 anorexic (AN) and 66 obese
      (OB)) and 49 healthy normal weight (NW). The plasma irisin levels were
      significantly elevated in the OB patients compared with the AN and NW patients.
      Irisin also correlated positively with body weight, BMI, and fat mass. The OB
      patients exhibited the highest REE and higher daily physical activity compared
      with the AN patients but lower activity compared with the NW patients. The irisin
      levels were inversely correlated with daily physical activity and directly
      correlated with REE. Fat mass contributed to most of the variability of the
      irisin plasma levels independently of the other studied parameters. Conclusion.
      Irisin levels are influenced by energy expenditure independently of daily
      physical activity but fat mass is the main contributing factor. 

PMID- 24864143
TI  - Intensive care unit admission after cytoreductive surgery and hyperthermic
      intraperitoneal chemotherapy. Is it necessary?
AB  - Introduction. Cytoreductive surgery (CS) with hyperthermic intraperitoneal
      chemotherapy (HIPEC) is a new approach for peritoneal carcinomatosis. However,
      high rates of complications are associated with CS and HIPEC due to treatment
      complexity; that is why some patients need stabilization and surveillance for
      complications in the intensive care unit. Objective. This study analyzed that ICU
      stay is necessary after HIPEC. Methods. 39 patients with peritoneal
      carcinomatosis were treated according to strict selection criteria with CS and
      HIPEC, with closed technique, and the chemotherapy administered were cisplatin 25
      mg/m(2)/L and mitomycin C 3.3 mg/m(2)/L for 90-minutes at 40.5 degrees C.
      Results. 26 (67%) of the 39 patients were transferred to the ICU. Major
      postoperative complications were seen in 14/26 patients (53%). The mean time on
      surgical procedures was 7.06 hours (range 5-9 hours). The mean blood loss was 939
      ml (range 100-3700 ml). The mean time stay in the ICU was 2.7 days. Conclusion.
      CS with HIPEC for the treatment of PC results in low mortality and high
      morbidity. Therefore, ICU stay directly following HIPEC should not be
      standardized, but should preferably be based on the extent or resections
      performed and individual patient characteristics and risk factors. Late
      complications were comparable to those reported after large abdominal surgery
      without HIPEC. 

PMID- 24864145
TI  - Breast magnetic resonance imaging and its impact on the surgical treatment of
      breast cancer.
AB  - Breast MRI focuses on the detection of multifocality, multicentricity, and
      bilaterality of newly diagnosed breast cancer. A retrospective study was carried
      out on 833 patients that were diagnosed and treated for breast cancer between
      January 2002 and December 2011. Patients were divided into two groups: those that
      had a presurgery breast MRI and those that did not. The two groups were compared
      on the basis of the several parameters. The aim of the study was to determine
      whether the use of MRI in breast cancer screening changes the initial treatment
      decision. In 18% of the patients, MRI revealed a multifocal or a multicentric
      unilateral breast cancer, a bilateral tumour, or a larger cancer than initially
      diagnosed. Most of these patients underwent a second-look breast ultrasound, with
      or without an additional biopsy. The percentage of mastectomies did not increase
      as a result of an MRI exam. Neoadjuvant chemotherapy was used more often and the
      percentage of reoperations decreased when an MRI was performed. 

PMID- 24864144
TI  - Importance of Diversity in the Oral Microbiota including Candida Species Revealed
      by High-Throughput Technologies.
AB  - Taking advantage of high-throughput technologies, deep sequencing of the human
      microbiome has revealed commensal bacteria independent of the ability to culture
      them. The composition of the commensal microbiome is dependent on bacterial
      diversity and the state of the host regulated by the immune system. Candida
      species are well known as components of the commensal oral microbiota. Candida
      species frequently colonize and develop biofilms on medical devices like dentures
      and catheters. Therefore, Candida biofilm on dentures leads to a decrease in the
      bacterial diversity and then to a change in the composition of the oral
      microbiota. A disturbance in the balance between commensal bacteria and the host
      immune system results in a switch from a healthy state to a diseased state even
      in the limited oral niche. 

PMID- 24864146
TI  - Dystrophic epidermolysis bullosa in pregnancy: a case report of the autosomal
      dominant subtype and review of the literature.
AB  - Epidermolysis bullosa (EB) is a group of inherited blistering skin diseases that
      vary widely in their pathogenesis and severity. There are three main categories
      of EB: simplex, junctional, and dystrophic. This classification is based on the
      level of tissue separation within the basement membrane zone and this is
      attributed to abnormalities of individual or several anchoring proteins that form
      the interlocking network spanning from the epidermis to the dermis underneath.
      Dystrophic EB results from mutations in COL7A1 gene coding for type VII collagen
      leading to blister formation within the dermis. Diagnosis ultimately depends on
      the patient's specific genetic mutation, but initial diagnosis can be made from
      careful examination and history taking. We present a pregnant patient known to
      have autosomal dominant dystrophic EB and discuss the obstetrical and neonatal
      outcome. The paper also reviews the current English literature on this rare skin
      disorder. 

PMID- 24864148
TI  - Complementary and alternative medicine on wikipedia: opportunities for
      improvement.
AB  - Wikipedia, a free and collaborative Internet encyclopedia, has become one of the
      most popular sources of free information on the Internet. However, there have
      been concerns over the quality of online health information, particularly that on
      complementary and alternative medicine (CAM). This exploratory study aimed to
      evaluate several page attributes of articles on CAM in the English Wikipedia. A
      total of 97 articles were analyzed and compared with eight articles of broad
      categories of therapies in conventional medicine using the Mann-Whitney U test.
      Based on the Wikipedia editorial assessment grading, 4% of the articles attained
      "good article" status, 34% required considerable editing, and 56% needed
      substantial improvements in their content. The median daily access of the
      articles over the previous 90 days was 372 (range: 7-4,214). The median word
      count was 1840 with a readability of grade 12.7 (range: 9.4-17.7). Medians of
      word count and citation density of the CAM articles were significantly lower than
      those in the articles of conventional medicine therapies. In conclusion, despite
      its limitations, the general public will continue to access health information on
      Wikipedia. There are opportunities for health professionals to contribute their
      knowledge and to improve the accuracy and completeness of the CAM articles on
      Wikipedia. 

PMID- 24864147
TI  - Rare appendicitis-like syndrome: the case of the obstructing broccoli.
AB  - The diagnosis of acute appendicitis can be somewhat obscure in a patient that
      presents with right lower quadrant abdominal pain. The advancement and ease of
      imaging have made CT scanning readily available in the emergency department.
      Management can be challenging when the patient has a high likelihood of
      appendicitis based on clinical suspicion and negative CT scan. The purpose of
      this case report is to demonstrate how an obstructing bezoar caused an
      appendicitis-like syndrome in a patient with negative CT scan and clinical
      diagnosis of acute appendicitis. This case report will discuss the appendicitis
      like syndrome of an obstructing bezoar and an approach at management. 

PMID- 24864149
TI  - Treating postlaparoscopic surgery shoulder pain with acupuncture.
AB  - Objective. The purpose of this study was to examine the effect of acupuncture on
      postlaparoscopic shoulder pain (PLSP) which is a common side effect in patients
      undergoing abdominal laparoscopic surgery. Methods. Patients with moderate to
      severe PLSP in spite of analgesic treatment, which were referred by the medical
      staff to the Complementary-Integrative Surgery Service (CISS) at our institution,
      were provided with acupuncture treatment. The severity of PLSP and of general
      pain was assessed using a Visual Analogue Scale (VAS) from 0 to 10. Pain
      assessment was conducted prior to and two hours following acupuncture treatment.
      Acupuncture treatment was individualized based on traditional Chinese medicine
      diagnosis. Results. A total of 25 patients were evaluated during a 14-month
      period, from March 2011 to May 2012. A significant reduction in PLSP (mean
      reduction of 6.4 +/- 2.3 P < 0.0001) and general pain (mean reduction 6.4 +/- 2.1
      P < 0.0001) were observed, and no significant side effects were reported.
      Conclusion. Individualized acupuncture treatments according to traditional
      Chinese medicine principles may improve postlaparoscopic shoulder pain and
      general pain when used in conjunction with conventional therapy. The primary
      findings of this study warrant verification in controlled studies. 

PMID- 24864150
TI  - Effects of Chinese Medicine Tong xinluo on Diabetic Nephropathy via Inhibiting
      TGF- beta 1-Induced Epithelial-to-Mesenchymal Transition.
AB  - Diabetic nephropathy (DN) is a major cause of chronic kidney failure and
      characterized by interstitial and glomeruli fibrosis. Epithelial-to-mesenchymal
      transition (EMT) plays an important role in the pathogenesis of DN. Tong xinluo
      (TXL), a Chinese herbal compound, has been used in China with established
      therapeutic efficacy in patients with DN. To investigate the molecular mechanism
      of TXL improving DN, KK-Ay mice were selected as models for the evaluation of
      pathogenesis and treatment in DN. In vitro, TGF- beta 1 was used to induce EMT.
      Western blot (WB), immunofluorescence staining, and real-time polymerase chain
      reaction (RT-PCR) were applied to detect the changes of EMT markers in vivo and
      in vitro, respectively. Results showed the expressions of TGF- beta 1 and its
      downstream proteins smad3/p-smad3 were greatly reduced in TXL group; meantime,
      TXL restored the expression of smad7. As a result, the expressions of collagen IV
      (Col IV) and fibronectin (FN) were significantly decreased in TXL group. In vivo,
      24 h-UAER (24-hour urine albumin excretion ratio) and BUN (blood urea nitrogen)
      were decreased and Ccr (creatinine clearance ratio) was increased in TXL group
      compared with DN group. In summary, the present study demonstrates that TXL
      successfully inhibits TGF- beta 1-induced epithelial-to-mesenchymal transition in
      DN, which may account for the therapeutic efficacy in TXL-mediated
      renoprotection. 

PMID- 24864151
TI  - Salidroside Reduces Cell Mobility via NF- kappa B and MAPK Signaling in LPS
      Induced BV2 Microglial Cells.
AB  - The unregulated activation of microglia following stroke results in the
      production of toxic factors that propagate secondary neuronal injury. Salidroside
      has been shown to exhibit protective effects against neuronal death induced by
      different insults. However, the molecular mechanisms responsible for the anti
      inflammatory activity of salidroside have not been elucidated clearly in
      microglia. In the present study, we investigated the molecular mechanism
      underlying inhibiting LPS-stimulated BV2 microglial cell mobility of salidroside.
      The protective effect of salidroside was investigated in microglial BV2 cell,
      subjected to stretch injury. Moreover, transwell migration assay demonstrated
      that salidroside significantly reduced cell motility. Our results also indicated
      that salidroside suppressed LPS-induced chemokines production in a dose-dependent
      manner, without causing cytotoxicity in BV2 microglial cells. Moreover,
      salidroside suppressed LPS-induced activation of nuclear factor kappa B (NF-
      kappa B) by blocking degradation of I kappa B alpha and phosphorylation of MAPK
      (p38, JNK, ERK1/2), which resulted in inhibition of chemokine expression. These
      results suggest that salidroside possesses a potent suppressive effect on cell
      migration of BV2 microglia and this compound may offer substantial therapeutic
      potential for treatment of ischemic strokes that are accompanied by microglial
      activation. 

PMID- 24864152
TI  - Propolis Reduces Phosphatidylcholine-Specific Phospholipase C Activity and
      Increases Annexin a7 Level in Oxidized-LDL-Stimulated Human Umbilical Vein
      Endothelial Cells.
AB  - To understand the mechanisms underlying the regulating dyslipidemia action of
      Chinese propolis and Brazilian green propolis, we investigated their effects on
      phosphatidylcholine-specific phospholipase C (PC-PLC) activity and annexin a7
      (ANXA7) level which play crucial roles in the control of the progress of
      atherosclerosis. Furthermore, active oxygen species (ROS) levels, nuclear factor
      KappaB p65 (NF- kappa B p65), and mitochondrial membrane potential (MMP) were
      also investigated in oxidized-LDL- (ox-LDL-) stimulated human umbilical vein
      endothelial cells (HUVECs). Our data indicated that the treatment of both types
      of propolis 12.5  MU g/mL significantly increased cell viability and attenuated
      apoptosis rate, increased ANXA7 level, and decreased PC-PLC activity. Both types
      of propolis also inhibited ROS generation as well as the subsequent MMP collapse,
      and NF- kappa B p65 activation induced by ox-LDL in HUVECs. Our results also
      indicated that Chinese propolis and Brazilian green propolis had similar
      biological activities and prevented ox-LDL induced cellular dysfunction in
      HUVECs. 

PMID- 24864153
TI  - A Platform for Screening Potential Anticholinesterase Fractions and Components
      Obtained from Anemarrhena asphodeloides Bge for Treating Alzheimer's Disease.
AB  - Alzheimer's disease (AD) is a neurodegenerative disease characterized by
      progressive memory loss and cognitive impairment. Cholinesterase inhibitors are
      widely used for the symptomatic treatment of Alzheimer's disease to enhance
      central cholinergic transmission. In this study, a bioactivity-oriented screening
      platform based on a modified Ellman's method and HPLC-QTOF MS technique was
      developed to rapidly screen active agents of Anemarrhena asphodeloides Bge. The
      60% ethanol fraction from an ethyl acetate extract exhibited the most potential
      anticholinesterase activity. Fifteen steroid saponins were identified by the mass
      spectrum, standards and literature reports. Twenty-five compounds were isolated
      from the active fraction. The results showed that compounds with the C6-C3-C6
      skeleton probably had both AChE and BuChE inhibitory activities. Xanthone and
      benzene derivatives exhibited no or little activity. Lignans showed weak BuChE
      inhibitory activity. The steroidal saponins demonstrated moderate or weak AChE
      inhibitory activity. 

PMID- 24864154
TI  - Effect of pumpkin seed oil on hair growth in men with androgenetic alopecia: a
      randomized, double-blind, placebo-controlled trial.
AB  - Pumpkin seed oil (PSO) has been shown to block the action of 5-alpha reductase
      and to have antiandrogenic effects on rats. This randomized, placebo-controlled,
      double-blind study was designed to investigate the efficacy and tolerability of
      PSO for treatment of hair growth in male patients with mild to moderate
      androgenetic alopecia (AGA). 76 male patients with AGA received 400 mg of PSO per
      day or a placebo for 24 weeks. Change over time in scalp hair growth was
      evaluated by four outcomes: assessment of standardized clinical photographs by a
      blinded investigator; patient self-assessment scores; scalp hair thickness; and
      scalp hair counts. Reports of adverse events were collected throughout the study.
      After 24 weeks of treatment, self-rated improvement score and self-rated
      satisfaction scores in the PSO-treated group were higher than in the placebo
      group (P = 0.013, 0.003). The PSO-treated group had more hair after treatment
      than at baseline, compared to the placebo group (P < 0.001). Mean hair count
      increases of 40% were observed in PSO-treated men at 24 weeks, whereas increases
      of 10% were observed in placebo-treated men (P < 0.001). Adverse effects were not
      different in the two groups. 

PMID- 24864156
TI  - Medicinal and edible fungi as an alternative medicine for treating age-related
      disease.

PMID- 24864155
TI  - Protective Effects of Bu-Shen-Huo-Xue Formula against 5/6 Nephrectomy-Induced
      Chronic Renal Failure in Rats.
AB  - Chronic renal failure (CRF) is a serious disease related to increasing incidence
      and prevalence as well as decline in quality of life. Bu-Shen-Huo-Xue formula
      (BSHX), one of traditional herbal formulations, has been clinically employed to
      treat CRF for decades, but the mechanisms involved have not been investigated. In
      the present study, we investigated the effects of BSHX on some closely related
      parameters in 5/6 nephrectomy CRF rats. Rats with CRF were divided into five
      groups, namely, one control group, one enalapril group, and three BSHX treatment
      groups (0.25, 0.5, and 1 g/kg.d). The rats subjected to sham operation were used
      as a normal control. After eight weeks of treatment, BSHX significantly decreased
      the levels of Scr and BUN, downregulated the mRNA expression levels of TGF-beta
      1, CTGF, NF-kappaB, TNF-alpha, and OPN, upregulated the mRNA expression of
      PPARgamma, and reduced in situ expression of fibronectin and laminins.
      Histological findings also showed significant amelioration of the damaged renal
      tissue. BSHX protects 5/6 nephrectomy rats against chronic renal failure probably
      via regulating the expression of TNF-alpha, NF-kappaB, TGF-beta 1, CTGF,
      PPARgamma, OPN, fibronectin, and laminins and is useful for therapy of CRF. 

PMID- 24864157
TI  - Qingkailing Suppresses the Activation of BV2 Microglial Cells by Inhibiting
      Hypoxia/Reoxygenation-Induced Inflammatory Responses.
AB  - Qingkailing (QKL) is a well-known composite extract used in traditional Chinese
      medicine. This extract has been extensively administered to treat the acute phase
      of cerebrovascular disease. Our previous experiments confirmed that QKL exerts an
      inhibitory effect on cerebral ischemia-induced inflammatory responses. However,
      whether QKL suppresses the activation of microglia, the primary resident immune
      cells in the brain, has yet to be determined. In this study, BV2 microglial cells
      were used to validate the protective effects of QKL treatment following ischemia
      reperfusion injury simulated via hypoxia/reoxygenation in vitro. Under these
      conditions, high expression levels of ROS, COX-2, iNOS, and p-p38 protein were
      detected. Following ischemia/reperfusion injury, QKL significantly increased the
      activity of BV2 cells to approximately the basal level by modulating microglial
      activation via inhibition of inflammatory factors, including TNF- alpha , COX-2,
      iNOS, and p-p38. However, QKL treatment also displayed dose-dependent differences
      in its inhibitory effects on p38 phosphorylation and inflammatory factor
      expression. 

PMID- 24864158
TI  - Phytotherapeutic information on plants used for the treatment of tuberculosis in
      eastern cape province, South Africa.
AB  - The current rate of deforestation in Africa constitutes a serious danger to the
      future of medicinal plants on this continent. Conservation of these medicinal
      plants in the field and the scientific documentation of our knowledge about them
      are therefore crucial. An ethnobotanical survey of plants used for the treatment
      of tuberculosis (TB) was carried out in selected areas of the Eastern Cape, South
      Africa. These areas were Hala, Ncera, Sheshegu, and Gquamashe, all within the
      Nkonkobe Municipality. One hundred informants were interviewed. The survey
      included the identification of scientific and vernacular names of the plants used
      for treatment of TB as well as the methods of preparation and administration, the
      part used, dosage, and duration of treatment. The survey revealed 30 plants
      belonging to 21 families which are commonly used by traditional healers for the
      treatment of TB and associated diseases. Of these plants Clausena anisata,
      Haemanthus albiflos, and Artemisia afra were the most cited. The leaves were the
      most common part used in the medicinal preparations. Our findings are discussed
      in relation to the importance of the documentation of medicinal plants. 

PMID- 24864159
TI  - Yiqi Huoxue Recipe Improves Heart Function through Inhibiting Apoptosis Related
      to Endoplasmic Reticulum Stress in Myocardial Infarction Model of Rats.
AB  - Objective. To explore the mechanism of cardioprotective effects of Chinese
      medicine, Yiqi Huoxue recipe, in rats with myocardial infarction- (MI-) induced
      heart failure. Methods. Male Sprague-Dawley rats underwent left anterior
      descending artery (LAD) ligation or sham operation. The surviving MI rats were
      divided randomly into three groups: MI (5 mL/kg/d NS by gavage), MI + Metoprolol
      Tartrate (MT) (12 mg/kg/d MT by gavage), and MI + Yiqi Huoxue (5 mL/kg recipe by
      gavage). And the sham operation rats were given 5 mL/kg/d normal saline.
      Treatments were given on the day following surgery for 4 weeks. Then rats were
      detected for heart structure and function by transthoracic echocardiography.
      Apoptosis in heart tissues was detected by TUNEL staining. To determine whether
      the endoplasmic reticulum (ER) stress response pathway is included in the
      cardioprotective function of the recipe, ER stress related proteins such as GRP78
      and caspase-12 were examined. Results. Yiqi Huoxue recipe attenuated heart
      function injury, reversed histopathological damage, alleviated myocardial
      apoptosis and inhibited ER stress in MI rats. Conclusion. All the results suggest
      that Yiqi Huoxue recipe improves the injured heart function maybe through
      inhibition of ER stress response pathway, which is a promising target in therapy
      for heart failure. 

PMID- 24864160
TI  - Wen-dan decoction improves negative emotions in sleep-deprived rats by regulating
      orexin-a and leptin expression.
AB  - Wen-Dan Decoction (WDD), a formula of traditional Chinese medicine, has been
      clinically used for treating insomnia for approximately 800 years. However, the
      therapeutic mechanisms of WDD remain unclear. Orexin-A plays a key role in the
      sleep-wake cycle, while leptin function is opposite to orexin-A. Thus, orexin-A
      and leptin may be important factors in sleep disorders. In this study, 48 rats
      were divided into control, model, WDD-treated, and diazepam-treated groups. The
      model of insomnia was produced by sleep deprivation (SD) for 14 days. The
      expressions of orexin-A, leptin, and their receptors in blood serum, prefrontal
      cortex, and hypothalamus were detected by enzyme-linked immunosorbent assay,
      immunohistochemistry, and real time PCR. Open field tests showed that SD
      increased both crossing movement (Cm) and rearing-movement (Rm) times. Orexin-A
      and leptin levels in blood serum increased after SD but decreased in brain
      compared to the control group. mRNA expressions of orexin receptor 1 and leptin
      receptor after SD were decreased in the prefrontal cortex but were increased in
      hypothalamus. WDD treatment normalized the behavior and upregulated orexin-A,
      leptin, orexin receptor 1 and leptin receptor in brain. The findings suggest that
      WDD treatment may regulate SD-induced negative emotions by regulating orexin-A
      and leptin expression. 

PMID- 24864161
TI  - Recent updates in the treatment of neurodegenerative disorders using natural
      compounds.
AB  - Neurodegenerative diseases are characterized by protein aggregates and
      inflammation as well as oxidative stress in the central nervous system (CNS).
      Multiple biological processes are linked to neurodegenerative diseases such as
      depletion or insufficient synthesis of neurotransmitters, oxidative stress,
      abnormal ubiquitination. Furthermore, damaging of blood brain barrier (BBB) in
      the CNS also leads to various CNS-related diseases. Even though synthetic drugs
      are used for the management of Alzheimer's disease, Parkinson's disease, autism,
      and many other chronic illnesses, they are not without side effects. The
      attentions of researchers have been inclined towards the phytochemicals, many of
      which have minimal side effects. Phytochemicals are promising therapeutic agents
      because many phytochemicals have anti-inflammatory, antioxidative as well as
      anticholinesterase activities. Various drugs of either synthetic or natural
      origin applied in the treatment of brain disorders need to cross the BBB before
      they can be used. This paper covers various researches related to phytochemicals
      used in the management of neurodegenerative disorders. 

PMID- 24864162
TI  - Possible benefits of singing to the mental and physical condition of the elderly.
AB  - BACKGROUND: The evaluation and management of stress are important for the
      prevention of both depression and cardiovascular disease. In addition, the
      maintenance of the oral condition of the elderly is essential to enable them to
      stay healthy, especially to prevent aspiration pneumonia and improve mental
      health in an aging society. Therefore, we examined the efficacy of singing on the
      oral condition, mental health status, and immunity of the elderly to determine if
      singing could contribute to the improvement of their physical condition. METHODS:
      Forty-four subjects (10 men, 34 women), aged 60 years or older, participated in
      this study. The efficacy of singing on mental health status and immunocompetence
      was examined by swallowing function, oral condition, blood, and saliva tests, as
      well as through questionnaires taken before and after singing. RESULTS: The
      results showed that the amount of saliva increased and the level of cortisol, a
      salivary stress marker, decreased after singing. The Visual Analog Scale (VAS)
      scores for feeling refreshed, comfortable, pleasurable, light-hearted, relieved,
      and relaxed; the tension and confusion subscale score; and the total mood
      disturbance (TMD) score of the Profile of Mood States (POMS) all showed
      improvements. Furthermore, the same tendencies were shown regardless of whether
      or not the subjects liked singing. CONCLUSIONS: Our results suggest that singing
      can be effective in improving the mental health and oral condition of the
      elderly.

PMID- 24864163
TI  - Bevacizumab in combination with chemotherapy for the treatment of advanced
      ovarian cancer: a systematic review.
AB  - As increased angiogenesis has been linked with the progression of ovarian cancer,
      a number of anti-angiogenic agents have been investigated, or are currently in
      development, as potential treatment options for patients with advanced disease.
      Bevacizumab, a recombinant monoclonal antibody against vascular endothelial
      growth factor, has gained European Medicines Agency approval for the front-line
      treatment of advanced epithelial ovarian cancer, fallopian tube cancer or primary
      peritoneal cancer in combination with carboplatin and paclitaxel, and for the
      treatment of first recurrence of platinum-sensitive ovarian cancer in combination
      with carboplatin and gemcitabine. We conducted a systematic literature review to
      identify available efficacy and safety data for bevacizumab in ovarian cancer as
      well as for newer anti-angiogenic agents in development. We analyzed published
      data from randomized, controlled phase II/III clinical trials enrolling women
      with ovarian cancer to receive treatment with bevacizumab. We also reviewed
      available data for emerging anti-angiogenic agents currently in phase II/III
      development, including trebananib, aflibercept, nintedanib, cediranib, imatinib,
      pazopanib, sorafenib and sunitinib. Significant efficacy gains were achieved with
      the addition of bevacizumab to standard chemotherapy in four randomized, double
      blind, phase III trials, both as front-line treatment (GOG-0218 and ICON7) and in
      patients with recurrent disease (OCEANS and AURELIA). The type and frequency of
      bevacizumab-related adverse events was as expected in these studies based on
      published data. Promising efficacy data have been published for a number of
      emerging anti-angiogenic agents in phase III development for advanced ovarian
      cancer. Further research is needed to identify predictive or prognostic markers
      of response to bevacizumab in order to optimize patient selection and treatment
      benefit. Data from phase III trials of newer anti-angiogenic agents in ovarian
      cancer are awaited. 

PMID- 24864164
TI  - A novel enzyme-linked immunosorbent assay for detection of Escherichia coli
      O157:H7 using immunomagnetic and beacon gold nanoparticles.
AB  - This paper presents a functional nanoparticle-enhanced enzyme-linked
      immunosorbent assay (FNP-ELISA) for detection of enterohemorrhagic Escherichia
      coli (EHEC) O157:H7. Immunomagnetic nanoparticles (IMMPs) conjugated with
      monoclonal anti-O157:H7 antibody were used to capture E. coli O157:H7. Beacon
      gold nanoparticles (B-GNPs) coated with polyclonal anti-O157:H7 and biotin single
      stranded DNA (B-DNA) were then subjective to immunoreaction with E. coli O157:H7,
      which was followed by streptavidin-horseradish peroxidase (Strep-HRP) conjugated
      with B-GNPs based on a biotin-avidin system. The solutions containing E. coli
      O157:H7, IMMPs, B-GNPs, and Strep-HRP were collected for detecting color change.
      The signal was significantly amplified with detection limits of 68 CFU mL(-1) in
      PBS and 6.8 * 10(2) to 6.8 * 10(3) CFU mL(-1) in the food samples. The FNP-ELISA
      method developed in this study was two orders of magnitude more sensitive than
      immunomagnetic separation ELISA (IMS-ELISA) and four orders of magnitude more
      sensitive than C-ELISA. The entire detection process of E. coli O157:H7 lasted
      only 3 h, and thus FNP-ELISA is considered as a time-saving method. 

PMID- 24864165
TI  - Neuroimaging in the evaluation of neonatal encephalopathy.
AB  - BACKGROUND AND OBJECTIVE: Computed tomography (CT) is still used for neuroimaging
      of infants with known or suspected neurologic disorders. Alternative neuroimaging
      options that do not expose the immature brain to radiation include MRI and
      cranial ultrasound. We aim to characterize and compare the use and findings of
      neuroimaging modalities, especially CT, in infants with neonatal encephalopathy.
      METHODS: The Vermont Oxford Network Neonatal Encephalopathy Registry enrolled
      4171 infants (>=36 weeks' gestation or treated with therapeutic hypothermia)
      between 2006 and 2010 who were diagnosed with encephalopathy in the first 3 days
      of life. Demographic, perinatal, and medical conditions were recorded, along with
      treatments, comorbidities, and outcomes. The modality, timing, and results of
      neuroimaging were also collected. RESULTS: CT scans were performed on 933 of 4107
      (22.7%) infants, and 100 of 921 (10.9%) of those received multiple CT scans.
      Compared with MRI, CT provided less detailed evaluation of cerebral injury in
      areas of prognostic significance, but was more sensitive than cranial ultrasound
      for hemorrhage and deep brain structural abnormalities. CONCLUSIONS: CT is
      commonly used for neuroimaging in newborn infants with neonatal encephalopathy
      despite concerns over potential harm from radiation exposure. The diagnostic
      performance of CT is inferior to MRI in identifying neonatal brain injury. Our
      data suggest that using cranial ultrasound for screening, followed by MRI would
      be more appropriate than CT at any stage to evaluate infants with neonatal
      encephalopathy.

PMID- 24864166
TI  - Validity of a single item food security questionnaire in Arctic Canada.
AB  - OBJECTIVES: Assess sensitivity and specificity of each of the 18 US Department of
      Agriculture (USDA) Household Food Security Scale Module (HFSSM) questionnaire
      items to determine whether a rapid assessment of child and adult food insecurity
      is feasible in an Inuit population. METHODS: Food insecurity prevalence was
      assessed by the 18-item USDA HFSSM in a randomized sample of Inuit households
      participating in the Inuit Health Survey and the Nunavut Inuit Child Health
      Survey. Questions were evaluated for sensitivity, specificity, predictive value
      (+/2), and total percent accuracy for adult and child food insecurity (yes/no).
      Child food security items were evaluated for both surveys. RESULTS: For children,
      the question "In the last 12 months, were there times when it was not possible to
      feed the children a healthy meal because there was not enough money?" had the
      best performance in both samples with a sensitivity and specificity of 92.3% and
      97.3%, respectively, for the Inuit Health Survey, and 88.5% and 95.4% for the
      Nunavut Inuit Child Health Survey. For adults, the question "In the last 12
      months, were there times when the food for you and your family just did not last
      and there was no money to buy more?" demonstrated a sensitivity of 93.0% and a
      specificity of 93.4%. CONCLUSIONS: Rapid assessment of child and adult food
      insecurity is feasible and may be a useful tool for health care and social
      service providers. However, as prevalence and severity of food insecurity change
      over time, rapid assessment techniques should not replace periodic screening by
      using the full USDA HFSSM questionnaire.

PMID- 24864167
TI  - Neurobehavioral comorbidities in children with active epilepsy: a population
      based study.
AB  - BACKGROUND: In addition to recurrent epileptic seizures, children with epilepsy
      can have coexisting cognitive and behavioral difficulties but the spectrum and
      prevalence of such difficulties are uncertain. METHODS: The Children with
      Epilepsy in Sussex Schools study is a prospective, community-based study
      involving school-aged children (5-15 years) with active epilepsy in a defined
      geographical area in the United Kingdom. Participants underwent comprehensive
      psychological assessment, including measures of cognition, behavior, and motor
      functioning. Consensus neurobehavioral diagnoses were made with respect to
      Diagnostic and Statistical Manual, Fourth Edition-Text Revision (DSM-IV-TR)
      criteria. RESULTS: A total of 85 children (74% of eligible population) were
      enrolled; 80% of children with active epilepsy had a DSM-IV-TR behavioral
      disorder and/or cognitive impairment (IQ ,85). Intellectual disability (ID) (IQ
      ,70) (40%), attention-deficit/hyperactivity disorder (ADHD) (33%), and autism
      spectrum disorder (ASD) (21%) were the most common neurobehavioral diagnoses. Of
      those who met criteria for a DSM-IV-TR behavioral disorder, only one-third had
      previously been diagnosed. Logistic regression revealed that seizures in the
      first 24 months compared with first seizures at 24 to 60 or 61+ months (odds
      ratio [OR] 13, 95% confidence interval 2.2-76.9; OR 21.3, 3.2-148.9) and
      polytherapy (OR 7.7, 1.6-36.3) were independently associated with ID and the
      presence of ID was associated with a diagnosis of ASD (OR 14.1, 2.3-87.1) after
      Bonferroni adjustment. Epilepsy-related factors did not independently predict the
      presence of behavioral disorders. CONCLUSIONS: Screening for neurobehavioral
      comorbidities should be an integral part of management in children with "active"
      epilepsy. There is a need for research to identify neurobiological mechanisms
      underpinning neurobehavioral impairments and studies to evaluate possible
      treatments.

PMID- 24864169
TI  - Treatment of Mycoplasma pneumoniae in pediatric lower respiratory infection.

PMID- 24864168
TI  - Application of the resource-based relative value scale system to pediatrics.
AB  - The majority of public and private payers in the United States currently use the
      Medicare Resource-Based Relative Value Scale as the basis for physician payment.
      Many large group and academic practices have adopted this objective system of
      physician work to benchmark physician productivity, including using it, wholly or
      in part, to determine compensation. The Resource-Based Relative Value Scale
      survey instrument, used to value physician services, was designed primarily for
      procedural services, leading to current concerns that American Medical
      Association/Specialty Society Relative Value Scale Update Committee (RUC) surveys
      may undervalue nonprocedural evaluation and management services. The American
      Academy of Pediatrics is represented on the RUC, the committee charged with
      maintaining accurate physician work values across specialties and age groups. The
      Academy, working closely with other primary care and subspecialty societies,
      actively pursues a balanced RUC membership and a survey instrument that will
      ensure appropriate work relative value unit assignments, thereby allowing
      pediatricians to receive appropriate payment for their services relative to other
      services.

PMID- 24864171
TI  - Whats and whys with neonatal CT.

PMID- 24864170
TI  - Safety and efficacy of filtered sunlight in treatment of jaundice in African
      neonates.
AB  - OBJECTIVES: Evaluate safety and efficacy of filtered-sunlight phototherapy (FS
      PT). METHODS: Term/late preterm infants #14 days old with clinically significant
      jaundice, assessed by total bilirubin (TB) levels, were recruited from a
      maternity hospital in Lagos, Nigeria. Sunlight was filtered with commercial
      window-tinting films that remove most UV and significant levels of infrared light
      and transmit effective levels of therapeutic blue light. After placing infants
      under an FS-PT canopy, hourly measurements of axillary temperatures, monitoring
      for sunburn, dehydration, and irradiances of filtered sunlight were performed.
      Treatment was deemed safe and efficacious if infants were able to stay in FS-PT
      for $5 hours and rate of rise of TB was ,0.2 mg/dL/h for infants #72 hours of age
      or TB decreased for infants .72 hours of age. RESULTS: A total of 227 infants
      received 258 days of FS-PT. No infant developed sunburn or dehydration. On 85
      (33%) of 258 treatment days, infants were removed briefly from FS-PT due to minor
      temperature-related adverse events. No infant met study exit criteria. FS-PT was
      efficacious in 92% (181/197) of evaluable treatment days. Mean 6 SD TB change was
      -0.06 6 0.19 mg/dL/h. The mean 6 SD (range) irradiance of FS-PT was 38 6 22 (2
      115) mW/cm2/nm, measured by the BiliBlanket Meter II. CONCLUSIONS: With
      appropriate monitoring, filtered sunlight is a novel, practical, and inexpensive
      method of PT that potentially offers safe and efficacious treatment strategy for
      management of neonatal jaundice in tropical countries where conventional PT
      treatment is not available.

PMID- 24864172
TI  - Care coordination and unmet specialty care among children with special health
      care needs.
AB  - OBJECTIVES: Care coordination and the medical home may ensure access to specialty
      care. Children with special health care needs (CSHCN) have higher rates of
      specialty care use and unmet need compared with the general pediatric population.
      We hypothesized that care coordination, regardless of whether it was provided in
      a medical home, would decrease unmet specialty care needs among CSHCN and that
      the effect of care coordination would be greater among low-income families.
      METHODS: Secondary data analysis of participants in the 2009-2010 National Survey
      of CSHCN who reported unmet specialty care needs and for whom care coordination
      and medical home status could be determined (n = 18 905). Logistic regression
      models explored the association of unmet need with care coordination and medical
      home status adjusting for household income. RESULTS: Approximately 9% of CSHCN
      reported having unmet specialty care needs. Care coordination was associated with
      reduced odds of unmet specialty care need (without a medical home, odds ratio:
      0.63, 95% confidence interval: 0.47-0.86; within a medical home, odds ratio:
      0.22, 95% confidence interval: 0.16-0.29) with a greater reduction among those
      receiving care coordination within a medical home versus those receiving care
      coordination without a medical home. We did not find differences in the impact of
      care coordination by percentage of the federal poverty level. CONCLUSIONS: Care
      coordination is associated with family report of decreased unmet specialty care
      needs among CSHCN independent of household income. The effect of care
      coordination is greater when care is received in a medical home.

PMID- 24864173
TI  - Rapid involuting congenital hemangioma in the setting of PHACE association.

PMID- 24864175
TI  - Enhancing the Work of the HHS National Vaccine Program in Global Immunizations.

PMID- 24864174
TI  - Treatment of mycoplasma pneumonia: a systematic review.
AB  - BACKGROUND AND OBJECTIVE: Children with community-acquired lower respiratory
      tract infection (CA-LRTI) commonly receive antibiotics for Mycoplasma pneumoniae.
      The objective was to evaluate the effect of treating M. pneumoniae in children
      with CA-LRTI. METHODS: PubMed, Cochrane Central Register of Controlled Trials,
      and bibliography review. A search was conducted by using Medical Subject Headings
      terms related to CA-LRTI and M. pneumoniae and was not restricted by language.
      Eligible studies included randomized controlled trials (RCTs) and observational
      studies of children #17 years old with confirmed M. pneumoniae and a diagnosis of
      CA-LRTI; each must have also compared treatment regimens with and without
      spectrum of activity against M. pneumoniae. Data extraction and quality
      assessment were completed independently by multiple reviewers before arriving at
      a consensus. Data were pooled using a random effects model. RESULTS: Sixteen
      articles detailing 17 studies were included. The most commonly selected primary
      outcome was symptomatic improvement. Nine studies examined M. pneumoniae
      treatment in CA-LRTI secondary to M. pneumoniae, and 5 RCTs met criteria for meta
      analysis. The suggested pooled risk difference of 0.12 (95% confidence interval,
      20.04 to 0.20) favoring treatment was not significantly different and
      demonstrated significant heterogeneity. Limitations included substantial bias and
      subjective outcomes within the individual studies, difficulty interpreting
      testing modalities, and the inability to correct for mixed infections or timing
      of intervention. CONCLUSIONS: We identified insufficient evidence to support or
      refute treatment of M. pneumoniae in CA-LRTI. These data highlight the need for
      well-designed, prospective RCTs assessing the effect of treating M. pneumoniae in
      CA-LRTI.

PMID- 24864176
TI  - Hypothermia and neonatal encephalopathy.
AB  - Data from large randomized clinical trials indicate that therapeutic hypothermia,
      using either selective head cooling or systemic cooling, is an effective therapy
      for neonatal encephalopathy. Infants selected for cooling must meet the criteria
      outlined in published clinical trials. The implementation of cooling needs to be
      performed at centers that have the capability to manage medically complex
      infants. Because the majority of infants who have neonatal encephalopathy are
      born at community hospitals, centers that perform cooling should work with their
      referring hospitals to implement education programs focused on increasing the
      awareness and identification of infants at risk for encephalopathy, and the
      initial clinical management of affected infants.

PMID- 24864177
TI  - Sirolimus improves pain in NF1 patients with severe plexiform neurofibromas.
AB  - Plexiform neurofibromas (PNs) are common and potentially debilitating
      complications of neurofibromatosis 1 (NF1). These benign nerve-sheath tumors are
      associated with significant pain and morbidity because they compress vital
      structures. The mammalian target of rapamycin (mTOR) pathway is a major mediator
      involved in tumor growth in NF1. We present 3 cases of patients with NF1, aged 8,
      16, and 17 years, followed for inoperable and symptomatic PNs; patients received
      sirolimus for life-threatening and painful neurofibromas after multidisciplinary
      consultation. Epidemiologic, clinical, and radiologic data were retrospectively
      collected. The volume of PNs did not differ between baseline and 12-month follow
      up and pain was alleviated, with withdrawal of analgesics in 2 cases at 6 months,
      and significantly decreased for the third case. Sirolimus for inoperable
      symptomatic PNs in patients with NF1 permitted stabilization of mass and produced
      unpredictable and important alleviation of pain in all cases with good tolerance.
      This treatment was proposed in extreme cases, in absence of therapeutic
      alternatives, after multidisciplinary consensus. The mTOR pathway may be both a
      major mediator of NF1 tumor growth and regulator of nociceptor sensitivity. mTOR
      inhibitors clinically used as anticancer and immunosuppressant drugs could be a
      potential treatment of chronic pain.

PMID- 24864178
TI  - Variation in outcomes of quality measurement by data source.
AB  - OBJECTIVE: To evaluate selected Children's Health Insurance Program
      Reauthorization Act claims-based quality measures using claims data alone,
      electronic health record (EHR) data alone, and both data sources combined.
      METHODS: Our population included pediatric patients from 46 clinics in the OCHIN
      network of community health centers, who were continuously enrolled in Oregon's
      public health insurance program during 2010. Within this population, we
      calculated selected pediatric care quality measures according to the Children's
      Health Insurance Program Reauthorization Act technical specifications within
      administrative claims. We then calculated these measures in the same cohort, by
      using EHR data, by using the technical specifications plus clinical data
      previously shown to enhance capture of a given measure. We used the k statistic
      to determine agreement in measurement when using claims versus EHR data. Finally,
      we measured quality of care delivered to the study population, when using a
      combined dataset of linked, patient-level administrative claims and EHR data.
      RESULTS: When using administrative claims data, 1.0% of children (aged 3-17) had
      a BMI percentile recorded, compared with 71.9% based on the EHR data (k agreement
      [k] # 0.01), and 72.0% in the combined dataset. Among children turning 2 in 2010,
      20.2% received all recommended immunizations according to the administrative
      claims data, 17.2% according to the EHR data (k = 0.82), and 21.4% according to
      the combined dataset. CONCLUSIONS: Children's care quality measures may not be
      accurate when assessed using only administrative claims. Adding EHR data to
      administrative claims data may yield more complete measurement.

PMID- 24864179
TI  - The Pediatric AIDS Corps: a 5-year evaluation.
AB  - BACKGROUND: The Baylor College of Medicine International Pediatric AIDS
      Initiative at Texas Children's Hospital created a global health corps named the
      Pediatric AIDS Corps (PAC) in June 2005. This report provides descriptive details
      and outputs for PAC over its first 5 years. METHODS: Demographic data were
      gathered about PAC physicians employed from July 2006 to June 2011. A 21-question
      survey was used to query PAC physicians about their experiences in the program.
      Data concerning clinical experiences and educational programs also were reviewed.
      RESULTS: A total of 128 physicians were employed with PAC. The median duration
      served was 22.7 months. Eighty-seven percent indicated that experience affected
      their future career choice, with half continuing to work with children and
      families living in resource-limited areas after they left PAC. Patient care was
      identified as the most rewarding part of their work (73%), whereas deaths (27%)
      were the most difficult. Baylor College of Medicine International Pediatric AIDS
      Initiative enrollment of HIV-infected children and adolescents into care and
      treatment increased from 6107 to 103 731 with the addition of PAC physicians.
      Approximately 500 local health care professionals per quarter benefited from HIV
      clinical attachments that were not available before PAC arrival. PAC physicians
      visited outreach sites providing in-depth HIV mentoring of local health care
      professionals, leading to 37% of the sites becoming self-sufficient. CONCLUSIONS:
      The positive evaluation by the PAC and the scale-up of clinical and educational
      programs support the recent calls for the development of a national global health
      corps program.

PMID- 24864181
TI  - National Adoption Center: Open Records.

PMID- 24864180
TI  - Iodine deficiency, pollutant chemicals, and the thyroid: new information on an
      old problem.
AB  - Many women of reproductive age in the United States are marginally iodine
      deficient, perhaps because the salt in processed foods is not iodized. Iodine
      deficiency, per se, can interfere with normal brain development in their
      offspring; in addition, it increases vulnerability to the effects of certain
      environmental pollutants, such as nitrate, thiocyanate, and perchlorate. Although
      pregnant and lactating women should take a supplement containing adequate iodide,
      only about 15% do so. Such supplements, however, may not contain enough iodide
      and may not be labeled accurately. The American Thyroid Association recommends
      that pregnant and lactating women take a supplement with adequate iodide. The
      American Academy of Pediatrics recommends that pregnant and lactating women also
      avoid exposure to excess nitrate, which would usually occur from contaminated
      well water, and thiocyanate, which is in cigarette smoke. Perchlorate is
      currently a candidate for regulation as a water pollutant. The Environmental
      Protection Agency should proceed with appropriate regulation, and the Food and
      Drug Administration should address the mislabeling of the iodine content of
      prenatal/lactation supplements.

PMID- 24864182
TI  - High doses of methylprednisolone in the management of caustic esophageal burns.
AB  - OBJECTIVE: Caustic substance ingestion in childhood is a public health issue in
      developing countries, and several management protocols have been proposed to
      prevent the resulting esophageal strictures. The role of corticosteroids in
      preventing corrosive-induced strictures is controversial. Our aim was to study
      the influence of high doses of corticosteroids in preventing esophageal
      strictures. METHODS: Eighty-three children with a mean age of 4.10 6 2.63 years
      and with grade IIb esophageal burns (an esophagogastroscopy was performed within
      24-48 hours of injury) due to corrosive substance ingestion were enrolled in our
      study between 2005 and 2008. Forty-two children (study group) received
      methylprednisolone (1 g/1.73 m2 per day for 3 days), ranitidine, ceftriaxone, and
      total parenteral nutrition. Forty-one children (control group) were administered
      the same regimen excluding methylprednisolone. Stricture development was compared
      between groups based on endoscopic and radiologic findings. RESULTS: During the
      endoscopic examination, stricture development was observed in 4 patients (10.8%)
      in the study group and in 12 patients (30%) in the control group. The difference
      was statistically significant (P = .038). The stricture development rate in the
      upper gastrointestinal system with barium meal was 14.3% and 45.0% in the study
      and control groups, respectively. The difference was statistically significant (P
      = .004). The duration of total parenteral nutrition was shorter in the study
      group compared with the control group (P = .001). High doses of
      methylprednisolone were well tolerated in the study group without any side
      effects. CONCLUSIONS: High doses of methylprednisolone used for the management of
      grade IIb esophageal burns may reduce stricture development.

PMID- 24864183
TI  - Intellectual, behavioral, and emotional functioning in children with syndromic
      craniosynostosis.
AB  - OBJECTIVES: To examine intellectual, behavioral, and emotional functioning of
      children who have syndromic craniosynostosis and to explore differences between
      diagnostic subgroups. METHODS: A national sample of children who have syndromic
      craniosynostosis participated in this study. Intellectual, behavioral, and
      emotional outcomes were assessed by using standardized measures: Wechsler
      Intelligence Scale for Children, Third Edition, Child Behavior Checklist (CBCL)/6
      18, Disruptive Behavior Disorder rating scale (DBD), and the National Institute
      of Mental Health Diagnostic Interview Schedule for Children. RESULTS: We included
      82 children (39 boys) aged 6 to 13 years who have syndromic craniosynostosis.
      Mean Full-Scale IQ (FSIQ) was in the normal range (M = 96.6; SD = 21.6). However,
      children who have syndromic craniosynostosis had a 1.9 times higher risk for
      developing intellectual disability (FSIQ < 85) compared with the normative
      population (P < .001) and had more behavioral and emotional problems compared
      with the normative population, including higher scores on the CBCL/6-18, DBD
      Total Problems (P < .001), Internalizing (P < .01), social problems (P < .001),
      attention problems (P < .001), and the DBD Inattention (P < .001). Children who
      have Apert syndrome had lower FSIQs (M = 76.7; SD = 13.3) and children who have
      Muenke syndrome had more social problems (P < .01), attention problems (P < .05),
      and inattention problems (P < .01) than normative population and with other
      diagnostic subgroups. CONCLUSIONS: Although children who have syndromic
      craniosynostosis have FSIQs similar to the normative population, they are at
      increased risk for developing intellectual disability, internalizing, social, and
      attention problems. Higher levels of behavioral and emotional problems were
      related to lower levels of intellectual functioning.

PMID- 24864184
TI  - Testing for drugs of abuse in children and adolescents.
AB  - Drug testing is often used as part of an assessment for substance use in children
      and adolescents. However, the indications for drug testing and guidance on how to
      use this procedure effectively are not clear. The complexity and invasiveness of
      the procedure and limitations to the information derived from drug testing all
      affect its utility. The objective of this clinical report is to provide guidance
      to pediatricians and other clinicians on the efficacy and efficient use of drug
      testing on the basis of a review of the nascent scientific literature, policy
      guidelines, and published clinical recommendations.

PMID- 24864185
TI  - Reducing injury risk from body checking in boys' youth ice hockey.
AB  - Ice hockey is an increasingly popular sport that allows intentional collision in
      the form of body checking for males but not for females. There is a two- to
      threefold increased risk of all injury, severe injury, and concussion related to
      body checking at all levels of boys' youth ice hockey. The American Academy of
      Pediatrics reinforces the importance of stringent enforcement of rules to protect
      player safety as well as educational interventions to decrease unsafe tactics. To
      promote ice hockey as a lifelong recreational pursuit for boys, the American
      Academy of Pediatrics recommends the expansion of nonchecking programs and the
      restriction of body checking to elite levels of boys' youth ice hockey, starting
      no earlier than 15 years of age.

PMID- 24864186
TI  - The 1901 St Louis incident: the first modern medical disaster.

PMID- 24864187
TI  - Youth ice hockey injuries over 16 years at a pediatric trauma center.
AB  - BACKGROUND: Youth ice hockey is an exciting sport with growing participation in
      the United States. Updated assessment of injury patterns is needed to determine
      risk factors for severe injury and develop preventive efforts. The purpose of
      this study was to evaluate our experience as a level 1 pediatric trauma center in
      Minnesota treating injured youth ice hockey players. METHODS: Children #18 years
      old who presented to our institution from July 1997 to July 2013 with an injury
      sustained while participating in ice hockey were identified. Patient demographic
      information, injury characteristics, and outcomes including use of computed
      tomography, hospital admission, and procedures were obtained. Age and gender
      specific patterns were determined for injuries and outcomes. RESULTS: Over 16
      years, 168 injuries in 155 children occurred, including 26 (15.5%) injuries in
      girls. Extremity injuries were most common, followed by traumatic brain injury.
      Injuries to the spine, face, and trunk were less common. Traumatic brain injury
      and injuries to the spine were most common in younger children (#14 years old)
      and girls, whereas injuries to the face were most common in older players ($15
      years old). Most injuries resulted from intentional contact. Admission to the
      hospital was needed in 65 patients, including 14 (8.3%) who needed intensive
      care. A major procedure was needed by 23.2% of patients because of their
      injuries. CONCLUSIONS: Youth ice hockey trauma can be severe, necessitating a
      thorough evaluation of injured children. Injury patterns are influenced by age
      and gender, providing an opportunity for targeted preventive efforts.

PMID- 24864188
TI  - Melatonin therapy prevents programmed hypertension and nitric oxide deficiency in
      offspring exposed to maternal caloric restriction.
AB  - Nitric oxide (NO) deficiency is involved in the development of hypertension, a
      condition that can originate early in life. We examined whether NO deficiency
      contributed to programmed hypertension in offspring from mothers with calorie
      restricted diets and whether melatonin therapy prevented this process. We
      examined 3-month-old male rat offspring from four maternal groups: untreated
      controls, 50% calorie-restricted (CR) rats, controls treated with melatonin
      (0.01% in drinking water), and CR rats treated with melatonin (CR + M). The
      effect of melatonin on nephrogenesis was analyzed using next-generation
      sequencing. The CR group developed hypertension associated with elevated plasma
      asymmetric dimethylarginine (ADMA, a nitric oxide synthase inhibitor), decreased
      L-arginine, decreased L-arginine-to-ADMA ratio (AAR), and decreased renal NO
      production. Maternal melatonin treatment prevented these effects. Melatonin
      prevented CR-induced renin and prorenin receptor expression. Renal angiotensin
      converting enzyme 2 protein levels in the M and CR + M groups were also
      significantly increased by melatonin therapy. Maternal melatonin therapy had long
      term epigenetic effects on global gene expression in the kidneys of offspring.
      Conclusively, we attributed these protective effects of melatonin on CR-induced
      programmed hypertension to the reduction of plasma ADMA, restoration of plasma
      AAR, increase of renal NO level, alteration of renin-angiotensin system, and
      epigenetic changes in numerous genes. 

PMID- 24864189
TI  - Physical exercise combined with whole-body cryotherapy in evaluating the level of
      lipid peroxidation products and other oxidant stress indicators in kayakers.
AB  - The influence of exercise combined with whole-body cryotherapy (WBC) on the
      oxidant/antioxidant balance in healthy men was assessed. The study included 16
      kayakers of the Polish National Team, aged 22.7 +/- 2.6, subjected to WBC (-120
      degrees C--145 degrees C; 3 min) twice a day for the first 10 days of a 19-day
      physical training cycle: pre exercise morning stimulation and post exercise
      afternoon recovery. Blood samples were taken on Day 0 (baseline) and on Days 5,
      11 and 19. The serum concentration of malondialdehyde (MDA), conjugated dienes
      (CD), thiobarbituric acid reactive substances (TBARS), protein carbonyls, vitamin
      E, urea, cortisol, and testosterone were determined, along with the glutathione
      peroxidase (GPx) activity, the total antioxidant capacity (TAC), and
      morphological blood parameters. On 5th day of exercise/WBC, the baseline GPx
      activity decreased by 15.1% (P < 0.05), while on 19th day, it increased by 19.7%
      (P < 0.05) versus Day 5. On Day 19 TBARS concentration decreased versus baseline
      and Day 5 (by 15.9% and 17.4%, resp.; P < 0.01). On 19 Day urea concentration
      also decreased versus 11 Day; however, on 5th and 11th days the level was higher
      versus baseline. Combining exercise during longer training cycles with WBC may be
      advantageous. 

PMID- 24864191
TI  - Factors Related to Sleep Disorders among Male Firefighters.
AB  - OBJECTIVES: The aim of this study was to investigate factors associated with
      sleep disorders in male firefighters working in a metropolitan city in South
      Korea. METHODS: Self-administered questionnaires including the Nordic
      Musculoskeletal Questionnaire, Korean Occupational Stress Scale-Short Form,
      Psychosocial Well-Being Index-Short Form, Pittsburg Sleep Quality Index, and Beck
      Depression Inventory-2 as well as surveys collecting socio-demographic
      characteristics and work-related factors were given to 730 male firefighters.
      After exclusion for missing data, 657 male firefighters were included, and
      logistic regression analysis adjusted for the work-related factors, psychosocial
      factors, and general risk factors were used to assess the relationship between
      sleep disorders and associated factors. RESULTS: The prevalence of sleep
      disorders was 48.7%. Shift work (adjusted OR 1.58, 95% CI = 1.02-2.45),
      musculoskeletal symptoms (adjusted OR 2.89, 95% CI = 2.02-4.14), and depression
      (adjusted OR 7.04 95% CI = 4.03-12.30) were associated with sleep disorders.
      CONCLUSIONS: Musculoskeletal symptoms, shift work, and depression are associated
      with sleep disorders. Integrated health management is needed to promote good
      sleep quality among firefighters.

PMID- 24864192
TI  - 25-gauge microincision vitrectomy to treat vitreoretinal disease in glaucomatous
      eyes after trabeculectomy.
AB  - Purpose. To determine the feasibility of using 25-gauge microincision vitrectomy
      surgery (25GMIVS) to treat vitreoretinal disease in glaucomatous eyes which have
      previously undergone trabeculectomy (TLE). Methods. A consecutive, interventional
      case series. We performed 25GMIVS in 15 glaucomatous eyes that had undergone TLE.
      Follow-up period was 11.5 months. Results. 25GMIVS was successfully used and led
      to improvement in visual acuity (P < 0.01). We performed 25GMIVS for
      proliferative diabetic retinopathy with neovascular glaucoma in 53% of eyes (8 of
      15). Although 3 eyes needed further TLE following 25GMIVS, final IOP was below 21
      mmHg in all eyes except one eye (93%) and was comparable to pre-25GMIVS IOP (P =
      0.20) without an increase in the number of glaucoma medications (P = 0.14).
      Conclusions. 25GMIVS is a feasible treatment for vitreoretinal disease in eyes
      with preexisting TLE, effective in both significantly improving BCVA and
      preserving the filtering bleb, while not excluding further glaucoma surgery. 

PMID- 24864190
TI  - Nitric oxide synthetic pathway in patients with microvascular angina and its
      relations with oxidative stress.
AB  - A decreased nitric oxide (NO) bioavailability and an increased oxidative stress
      play a pivotal role in different cardiovascular pathologies. As red blood cells
      (RBCs) participate in NO formation in the bloodstream, the aim of this study was
      to outline the metabolic profile of L-arginine (Arg)/NO pathway and of oxidative
      stress status in RBCs and in plasma of patients with microvascular angina (MVA),
      investigating similarities and differences with respect to coronary artery
      disease (CAD) patients or healthy controls (Ctrl). Analytes involved in Arg/NO
      pathway and the ratio of oxidized and reduced forms of glutathione were measured
      by LC-MS/MS. The arginase and the NO synthase (NOS) expression were evaluated by
      immunofluorescence staining. RBCs from MVA patients show increased levels of NO
      synthesis inhibitors, parallel to that found in plasma, and a reduction of NO
      synthase expression. When summary scores were computed, both patient groups were
      associated with a positive oxidative score and a negative NO score, with the CAD
      group located in a more extreme position with respect to Ctrl. This finding
      points out to an impairment of the capacity of RBCs to produce NO in a
      pathological condition characterized mostly by alterations at the microvascular
      bed with no significant coronary stenosis. 

PMID- 24864193
TI  - Impaired corneal biomechanical properties and the prevalence of keratoconus in
      mitral valve prolapse.
AB  - Objective. To investigate the biomechanical characteristics of the cornea in
      patients with mitral valve prolapse (MVP) and the prevalence of keratoconus (KC)
      in MVP. Materials and Methods. Fifty-two patients with MVP, 39 patients with KC,
      and 45 control individuals were recruited in this study. All the participants
      underwent ophthalmologic examination, corneal analysis with the Sirius system
      (CSO), and the corneal biomechanical evaluation with Reichert ocular response
      analyzer (ORA). Results. KC was found in six eyes of four patients (5.7%) and
      suspect KC in eight eyes of five patients (7.7%) in the MVP group. KC was found
      in one eye of one patient (1.1%) in the control group (P = 0.035). A significant
      difference occurred in the mean CH and CRF between the MVP and control groups (P
      = 0.006 and P = 0.009, resp.). All corneal biomechanical and topographical
      parameters except IOPcc were significantly different between the KC-MVP groups (P
      < 0.05). Conclusions. KC prevalence is higher than control individuals in MVP
      patients and the biomechanical properties of the cornea are altered in patients
      with MVP. These findings should be considered when the MVP patients are evaluated
      before refractive surgery. 

PMID- 24864194
TI  - Attentional capture and inhibition of saccades after irrelevant and relevant
      cues.
AB  - Attentional capture is usually stronger for task-relevant than irrelevant
      stimuli, whereas irrelevant stimuli can trigger equal or even stronger amounts of
      inhibition than relevant stimuli. Capture and inhibition, however, are typically
      assessed in separate trials, leaving it open whether or not inhibition of
      irrelevant stimuli is a consequence of preceding attentional capture by the same
      stimuli or whether inhibition is the only response to these stimuli. Here, we
      tested the relationship between capture and inhibition in a setup allowing for
      estimates of the capture and inhibition based on the very same trials. We
      recorded saccadic inhibition after relevant and irrelevant stimuli. At the same
      time, we recorded the N2pc, an event-related potential, reflecting initial
      capture of attention. We found attentional capture not only for, relevant but
      importantly also for irrelevant stimuli, although the N2pc was stronger for
      relevant than irrelevant stimuli. In addition, inhibition of saccades was the
      same for relevant and irrelevant stimuli. We conclude with a discussion of the
      mechanisms that are responsible for these effects. 

PMID- 24864196
TI  - Association between Ocular Pseudoexfoliation and Sensorineural Hearing Loss.
AB  - Background. Our study aimed to investigate an association between ocular
      pseudoexfoliation (PXF) and sensorineural hearing loss (SNHL) and to compare them
      with age and sex matched controls without pseudoexfoliation. Method. This was a
      case-control study of 123 patients which included 68 cases with PXF (at least one
      eye) and 55 controls without pseudoexfoliation. Pure-tone audiometry (PTA) was
      done for these patients at sound frequencies taken as important for speech
      comprehension, that is, 250 Hertz (Hz), 500 Hz, 1000 Hz, and 2000 Hz. Results.
      There were 41 patients with pseudoexfoliation syndrome (PXE) and 27 with
      pseudoexfoliative glaucoma (PXEG). The majority of patients with hearing loss
      (60%; n = 51) were PXF patients and the remaining 40% (n = 34) were controls.
      Below average hearing thresholds were significantly higher in the
      pseudoexfoliation group compared to the control group (P = 0.01; odds ratio (OR),
      3.00; 95% confidence interval (CI), 1.25-7.19). However, there was no significant
      difference in the mean hearing threshold levels between the three groups (PXE,
      PXEG, and controls) in either ear (ANOVA, right ear: P = 0.46 and left ear P =
      0.36). Conclusion. Our study found an association between PXF and SNHL,
      confirming that PXF can involve organs in the body other than the eye. 

PMID- 24864195
TI  - Gender Differences in Behcet's Disease Associated Uveitis.
AB  - Behcet's disease is a systemic vasculitis of unknown etiology, characterized by
      oral and genital ulceration, skin lesions, and uveitis as well as vascular,
      central nervous system, and gastrointestinal system involvement. It is prevalent
      in the Middle East, Mediterranean, and Eastern Asia. The aim of this review is to
      evaluate the gender differences in clinical manifestations of Behcet's disease,
      treatment responses, mortality, and morbidity. Behcet's disease has been reported
      to be more prevalent in males from certain geographic regions and particular
      ethnic groups; however, recent reports indicate more even gender distribution
      across the world. There are gender differences in clinical manifestations and
      severity of the disease. Ocular manifestations, vascular involvement, and
      neurologic symptoms are more frequently reported in male patients whereas oral
      and genital ulcers, skin lesions, and arthritis occur more frequently in female
      patients. The disease can have a more severe course in males, and overall
      mortality rate is significantly higher among young male patients. 

PMID- 24864197
TI  - "En-face" spectral-domain optical coherence tomography findings in multiple
      evanescent white dot syndrome.
AB  - Purpose. The recent use of "en-face" enhanced-depth imaging spectral-domain
      optical coherence tomography (EDI SD-OCT) helps distinguish the retinal layers
      involved in the physiopathology of multiple evanescent white dot syndrome
      (MEWDS). Methods. Four patients presenting with MEWDS underwent a comprehensive
      ocular examination including C-scan ("en-face") EDI SD-OCT at the initial visit
      and during follow-up. Results. C-scans combined with the other multimodal imaging
      enabled the visualization of retinal damage. Acute lesions appeared as diffuse
      and focal disruptions occurring in the ellipsoid and interdigitation zones. The
      match between autofluorescence imaging, indocyanine green angiography, and "en
      face" OCT helped identify the acute microstructural damages in the outer retina
      further than the choroid. Follow-up using "en-face" EDI-OCT revealed progressive
      and complete recovery of the central outer retinal layers. Conclusion. "En-face"
      EDI SD-OCT identified the site of initial damage in MEWDS as the photoreceptors
      and the interdigitation layers rather than the choroid. Moreover, "en-face" OCT
      is helpful in the follow-up of these lesions by being able to show the recovery
      of the outer retinal layers. 

PMID- 24864198
TI  - Mercury, autoimmunity, and environmental factors on cheyenne river sioux tribal
      lands.
AB  - Mercury (Hg), shown to induce autoimmune disease in rodents, is a ubiquitous
      toxicant throughout Cheyenne River Sioux Tribe (CRST) lands. CRST members may be
      exposed to Hg through fish consumption (FC), an important component of native
      culture that may supplement household subsistence. Our goals were to ascertain
      whether total blood Hg levels (THg) reflect Hg exposure through FC and smoking,
      and determine whether THg is associated with the presence of anti-nuclear
      antibody (ANA) and specific autoantibodies (sAuAb). We recruited 75 participants
      who regularly consume fish from CRST waters. Hg exposure through FC and smoking
      were assessed via questionnaires. Whole blood samples were collected from
      participants, and THg was measured using ICP-MS. ANA and sAuAb in serum were
      modeled using demographic and exposure information as predictors. Female gender,
      age, and FC were significant predictors of THg and sAuAb; self-reported smoking
      was not. 31% of participants tested positive for ANA >= 2+. Although ANA was not
      significantly associated with Hg, the interactions of gender with Hg and
      proximity to arsenic deposits were statistically significant (P < 0.05). FC
      resulted in a detectable body burden of Hg, but THg alone did not correlate with
      the presence of ANA or sAuAb in this population. 

PMID- 24864199
TI  - Lifestyle intervention involving calorie restriction with or without aerobic
      exercise training improves liver fat in adults with visceral adiposity.
AB  - OBJECTIVE: To evaluate the effect of calorie restriction-induced weight loss with
      or without aerobic exercise on liver fat. METHODS: Thirty-three adults with
      visceral adiposity were divided into calorie restriction (CR; n = 18) or CR and
      aerobic exercise (CR + Ex; n = 15) groups. Target energy intake was 25 kcal/kg of
      ideal body weight. The CR + Ex group had a targeted exercise time of 300 min/wk
      or more at lactate threshold intensity for 12 weeks. RESULTS: Reductions in body
      weight (CR, -5.3 +/- 0.8 kg; CR + Ex, -5.1 +/- 0.7 kg), fat mass (CR, -4.9 +/-
      0.9 kg; CR + Ex, -4.4 +/- 0.6 kg), and visceral fat (CR, -24 +/- 5 cm2; CR + Ex, 
      37 +/- 5 cm2) were not statistically different between groups. Liver fat
      decreased significantly in both groups, with no difference between groups. Change
      in maximal oxygen uptake was significantly greater in the CR + Ex group than in
      the CR group (CR, -0.7 +/- 0.7 mL/kg/min; CR + Ex, 2.9 +/- 1.0 mL/kg/min).
      CONCLUSION: Both CR and CR + Ex resulted in an improved reduction in liver fat;
      however, there was no additive effect of exercise training.

PMID- 24864201
TI  - HIV Prevention Messages Targeting Young Latino Immigrant MSM.
AB  - Young Latino immigrant men who have sex with men (MSM) are at risk for HIV and
      for delayed diagnosis. A need exists to raise awareness about HIV prevention in
      this population, including the benefits of timely HIV testing. This project was
      developed through collaboration between University of WA researchers and Entre
      Hermanos, a community-based organization serving Latinos. Building from a
      community-based participatory research approach, the researchers developed a
      campaign that was executed by Activate Brands, based in Denver, Colorado. The
      authors (a) describe the development of HIV prevention messages through the
      integration of previously collected formative data; (b) describe the process of
      translating these messages into PSAs, including the application of a marketing
      strategy; (c) describe testing the PSAs within the Latino MSM community; and (c)
      determine a set of important factors to consider when developing HIV prevention
      messages for young Latino MSM who do not identify as gay. 

PMID- 24864202
TI  - Cormic index profile of children with sickle cell anaemia in lagos, Nigeria.
AB  - Background. Sickle cell disorders are known to have a negative effect on linear
      growth. This could potentially affect proportional growth and, hence, Cormic
      Index. Objective. To determine the Cormic Index in the sickle cell anaemia
      population in Lagos. Methodology. A consecutive sample of 100 children with
      haemoglobin genotype SS, aged eight months to 15 years, and 100 age and sex
      matched controls (haemoglobin genotype AA) was studied. Sitting height (upper
      segment) and full length or height were measured. Sitting height was then
      expressed as a percentage of full length/height (Cormic Index). Results. The mean
      Cormic Index decreased with age among primary subjects (SS) and AA controls. The
      overall mean Cormic Index among primary subjects was comparable to that of
      controls (55.0 +/- 4.6% versus 54.5 +/- 5.2%; 54.8 +/- 4.5% versus 53.6 +/- 4.9%)
      in boys and girls, respectively. In comparison with AA controls, female children
      with sickle cell anaemia who were older than 10 years had a significantly lower
      mean Cormic Index. Conclusion. There was a significant negative relationship
      between Cormic Index and height in subjects and controls irrespective of gender.
      Similarly, a significant negative correlation existed between age, sitting
      height, subischial leg length, weight, and Cormic Index in both subjects and
      controls. 

PMID- 24864200
TI  - Early life exposure to fructose and offspring phenotype: implications for long
      term metabolic homeostasis.
AB  - The consumption of artificially sweetened processed foods, particularly high in
      fructose or high fructose corn syrup, has increased significantly in the past few
      decades. As such, interest into the long term outcomes of consuming high levels
      of fructose has increased significantly, particularly when the exposure is early
      in life. Epidemiological and experimental evidence has linked fructose
      consumption to the metabolic syndrome and associated comorbidities-implicating
      fructose as a potential factor in the obesity epidemic. Yet, despite the
      widespread consumption of fructose-containing foods and beverages and the rising
      incidence of maternal obesity, little attention has been paid to the possible
      adverse effects of maternal fructose consumption on the developing fetus and long
      term effects on offspring. In this paper we review studies investigating the
      effects of fructose intake on metabolic outcomes in both mother and offspring
      using human and experimental studies. 

PMID- 24864203
TI  - Continuous professional development for GPs: experience from Denmark.
AB  - BACKGROUND AND OBJECTIVES: Continuous professional development (CPD) for Danish
      general practitioners (GPs) is voluntary and based on funded accredited
      activities. There is an ongoing discussion on how to improve this current system
      by introducing mandatory elements. To inform this debate, we set out to identify
      GPs' current use of CPD and to explore the motives behind their choices. METHODS:
      A mixed-methods study with a combined qualitative and quantitative approach was
      used. In 2012, two focus group interviews were conducted, followed up the same
      year by an online questionnaire sent to 1079 randomly chosen Danish GPs. RESULTS:
      Focus groups: CPD activities are chosen based on personal needs analysis, and in
      order to be professionally updated, to meet engaged colleagues and to prevent
      burnout. GPs also attend CPD to assess their own pre-existing level of
      competence. CPD activities need to be experienced as being both meaningful and
      relevant in order to have an impact. Questionnaire: The response rate was
      686/1079 (63%). GPs spend on average 10.5 days per year on accredited, voluntary
      CPD activities. Workplace-related CPD activities and practice-based small group
      learning played a significant role. The main motivation for choice of CPD
      activities included academic interest, experience of patient-related problems in
      their own surgeries and medical topics where the GPs felt insufficiently
      confident. CONCLUSIONS: Danish GPs are frequent users of voluntary accredited
      CPD. Their CPD choices are motivated by topics strengthening their professional
      capacity and preventing burnout. There would seem to be no need for a mandatory
      system.

PMID- 24864204
TI  - Health disparities in genomics and genetics.

PMID- 24864205
TI  - Assessing and enhancing health care providers' response to domestic violence.
AB  - This study aimed to examine possible changes from 2008 to 2012 in the skills of
      health care staff in identifying and intervening in domestic violence (DV). A
      longitudinal descriptive study design with volunteer samples (baseline; n = 68,
      follow-up; n = 100) was used to acquire information regarding the present state
      and needs of the staff in practices related to DV. The results of the baseline
      survey were used as a basis for planning two interventions: staff training and
      drafting practical guidelines. Information was collected by questionnaires from
      nurses, physicians, and social workers and supplemented by responses from the
      interviews. The data were analysed using both quantitative and qualitative
      methods. A chi-square test was used to test the statistical significance of the
      data sets. In addition, participants' quotes are used to describe specific
      phenomena or issues. The comparison showed that overall a small positive change
      had taken place between the study periods. However, the participants were aware
      of their own shortcomings in identifying and intervening in DV. Changes happen
      slowly, and administrative support is needed to sustain such changes. Therefore,
      this paper offers recommendations to improve health care providers' response to
      DV. Moreover, there is a great need for evaluating the training programme used. 

PMID- 24864207
TI  - A New Proposal for Learning Curve of TEP Inguinal Hernia Repair: Ability to
      Complete Operation Endoscopically as a First Phase of Learning Curve.
AB  - Background. The exact nature of learning curve of totally extraperitoneal
      inguinal hernia and the number required to master this technique remain
      controversial. Patients and Methods. We present a retrospective review of a
      single surgeon experience on patients who underwent totally extraperitoneal
      inguinal hernia repair. Results. There were 42 hernias (22 left- and 20 right
      sided) in 39 patients with a mean age of 48.8 +/- 15.1 years. Indirect, direct,
      and combined hernias were present in 18, 12, and 12 cases, respectively. The mean
      operative time was 55.1 +/- 22.8 minutes. Peritoneal injury occurred in 9 cases
      (21.4%). Conversion to open surgery was necessitated in 7 cases (16.7%). After
      grouping of all patients into two groups as cases between 1-21 and 22-42, it was
      seen that the majority of peritoneal injuries (7 out of 9, 77.8%, P = 0.130) and
      all conversions (P = 0.001) occurred in the first 21 cases. Conclusions. Learning
      curve of totally extraperitoneal inguinal hernia repair can be divided into two
      consequent steps: immediate and late. At least 20 operations are required for
      gaining anatomical knowledge and surgical pitfalls based on the ability to
      perform this operation without conversion during immediate phase. 

PMID- 24864206
TI  - Pilot program to improve self-management of patients with heart failure by
      redesigning care coordination.
AB  - Objectives. We tested both an educational and a care coordination element of
      health care to examine if better disease-specific knowledge leads to successful
      self-management of heart failure (HF). Background. The high utilization of health
      care resources and poor patient outcomes associated with HF justify tests of
      change to improve self-management of HF. Methods. This prospective study tested
      two components of the Chronic Care Model (clinical information systems and self
      management support) to improve outcomes in the self-management of HF among
      patients who received intensive education and care coordination during their
      acute care stay. A postdischarge follow-up phone call assessed their knowledge of
      HF self-management compared to usual care patients. Results. There were 20
      patients each in the intervention and usual care groups. Intervention patients
      were more likely to have a scale at home, write down their weight, and practice
      new or different health behaviors. Conclusion. Patients receiving more intensive
      education knew more about their disease and were better able to self-manage their
      weight compared to patients receiving standard care. 

PMID- 24864208
TI  - Psychological Reactions and Persistent Facial Pain following Enucleation.
AB  - Background. Enucleation is a psychologically and physically traumatic event
      associated with chronic pain. It would be desirable to better predict which
      patients will have pain after surgery. Methods. A cross-sectional postal
      questionnaire study of adults undergoing enucleation captured the demographic
      details, Pain Quality Assessment Scale (PQAS), Pain Catastrophizing Scale (PCS),
      and the Facial Pain Assessment questionnaire. Patients were classified as
      suffering from chronic pain if they reported a pain score of >1 out of 10 on the
      numerical pain score (NRS). Results. Seventeen of 60 adults participated in the
      study. 47% of patients reported chronic pain (mean pain score = 1.4 +/- 0.7, n =
      17); 25% experienced pain daily. No difference in age, surgical side, reason for
      surgery, or the duration of time since the surgery was noted. All patients had
      low PQAS scores and 50% of individuals with persistent pain were concerned about
      their facial appearance. There was no significant difference in the level of
      catastrophization noted in patients with or without pain or between the subgroups
      (rumination, magnification, or helplessness). Conclusions. Although persistent
      pain following enucleation affected a significant number of patients, the pain
      intensity was mild. Enucleation influenced the physical perception some
      individuals had of themselves. 

PMID- 24864209
TI  - "Sometimes It's Difficult to Have a Normal Life": Results from a Qualitative
      Study Exploring Caregiver Burden in Schizophrenia.
AB  - Objectives. As a disease typified by early onset and chronic disease course,
      caring for a person with schizophrenia may have a significant impact on
      caregivers' lives. This study aimed to investigate the subjective experiences of
      caregivers of people with schizophrenia as a means of understanding "caregiver
      burden" in this population. Methods. Face-to-face qualitative interviews were
      conducted with a diverse sample of 19 US-English speaking caregivers of people
      with schizophrenia (who were at least moderately ill). Interview transcripts were
      analyzed using grounded theory methods and findings used to inform the
      development of a preliminary conceptual model outlining caregivers' experiences.
      Results. Findings support assertions that people with schizophrenia were largely
      dependent upon caregivers for the provision of care and caregivers subsequently
      reported lacking time for themselves and their other responsibilities (e.g.,
      family and work). Caregiver burden frequently manifested as detriments in
      physical (e.g., fatigue, sickness) and emotional well-being (e.g., depression and
      anxiety). Conclusions. Caring for a person with schizophrenia has a significant
      impact on the lives of informal (unpaid) caregivers and alleviating caregiver
      burden is critical for managing individual and societal costs. Future research
      should concentrate on establishing reliable and valid means of assessing burden
      among caregivers of persons with schizophrenia to inform the development and
      evaluation of interventions for reducing this burden. 

PMID- 24864211
TI  - Fetomaternal outcome in severe preeclamptic women undergoing emergency cesarean
      section under either general or spinal anesthesia.
AB  - This prospective observational study compared the effects of general and spinal
      anesthesia in 173 severe preeclamptic women undergoing emergency cesarean
      section. 146 (84.5%) patients underwent spinal anesthesia (SA) and 27 (15.5%)
      patients had general anesthesia (GA). Most of the patients were primigravid and
      nulliparous. Intraoperatively SA group required more intravenous fluid and
      vasopressor support, while GA group required more preoperative labetalol
      injection for blood pressure control. Overall 13.3% of patients required critical
      care, particularly GA group (44.4% versus 7.5%; P < 0.001). Patients receiving GA
      had a higher mortality (25.9% versus 1.4%; P < 0.001). The length of hospital
      stay was comparable. Significantly more neonates of patients receiving GA were
      found to be preterm (77.8% versus 44.5%; P < 0.01) and required advanced
      resuscitation. GA group also had higher neonatal mortality (29.6% versus 11%; P <
      0.05). To conclude, severe preeclamptic mothers receiving general anesthesia and
      their babies required more critical care support. Maternal as well as neonatal
      mortality was significantly higher with general anesthesia. 

PMID- 24864210
TI  - Exploring Drug Targets in Isoprenoid Biosynthetic Pathway for Plasmodium
      falciparum.
AB  - Emergence of rapid drug resistance to existing antimalarial drugs in Plasmodium
      falciparum has created the need for prediction of novel targets as well as leads
      derived from original molecules with improved activity against a validated drug
      target. The malaria parasite has a plant plastid-like apicoplast. To overcome the
      problem of falciparum malaria, the metabolic pathways in parasite apicoplast have
      been used as antimalarial drug targets. Among several pathways in apicoplast,
      isoprenoid biosynthesis is one of the important pathways for parasite as its
      multiplication in human erythrocytes requires isoprenoids. Therefore targeting
      this pathway and exploring leads with improved activity is a highly attractive
      approach. This report has explored progress towards the study of proteins and
      inhibitors of isoprenoid biosynthesis pathway. For more comprehensive analysis,
      antimalarial drug-protein interaction has been covered. 

PMID- 24864212
TI  - Basal cell carcinoma of the head and neck region: a retrospective analysis of
      completely excised 331 cases.
AB  - The aim of the study is to analyze all completely excised BCCs in the head and
      neck region with regard to age, sex, personal and familial history, skin type,
      tumor localization and size, histopathological subtype of tumor, reconstruction
      method, and recurrence rates. Incompletely excised BCCs were not included in this
      study since incomplete excision is the most important preventable risk factor for
      recurrence. In 320 patients, 331 lesions were retrospectively evaluated by
      dividing into the following 8 subunits: scalp, frontotemporal, orbital, nose,
      cheek, auricula, perioral, and chin-neck area. Most of the patients were in 60-70
      age group (34.7%). The nose (32.3%) was the most common site of presentation.
      Clinically, all lesions and, histopathologically, most of the lesions (42.2%)
      presented were of the nodular type. All cases of recurrence after complete
      excision (n = 9, 2.7%) were located in the median parts of the head and neck
      region and were mainly diagnosed histopathologically as sclerotic and
      micronodular. Even though completely excised, head and neck region BCCs,
      especially which are more prone to recurrence due to anatomical and
      histopathological properties, should be more closely monitored in order to
      decrease morbidity and health care costs. 

PMID- 24864213
TI  - Obesity and the Odds of Weight Gain following Androgen Deprivation Therapy for
      Prostate Cancer.
AB  - Background. Increasing body mass index (BMI) is associated with increased risk of
      mortality; however, quantifying weight gain in men undergoing androgen
      deprivation therapy (ADT) for prostate cancer (PC) remains unexplored. Methods.
      Between 1995 and 2001, 206 men were enrolled in a randomized trial evaluating the
      survival difference of adding 6 months of ADT to radiation therapy (RT). BMI
      measurements were available in 171 men comprising the study cohort. The primary
      endpoint was weight gain of >=10 lbs by 6-month followup. Logistic regression
      analysis was performed to assess whether baseline BMI or treatment received was
      associated with this endpoint adjusting for known prognostic factors. Results. By
      the 6-month followup, 12 men gained >=10 lbs, of which 10 (83%) received RT + ADT
      and, of these, 7 (70%) were obese at randomization. Men treated with RT as
      compared to RT + ADT were less likely to gain >=10 lbs (adjusted odds ratio
      (AOR): 0.18 [95% CI: 0.04-0.89]; P = 0.04), whereas this risk increased with
      increasing BMI (AOR: 1.15 [95% CI: 1.01-1.31]; P = 0.04). Conclusions.
      Consideration should be given to avoid ADT in obese men with low- or favorable
      intermediate risk PC where improved cancer control has not been observed, but
      shortened life expectancy from weight gain is expected. 

PMID- 24864214
TI  - Statistical Optimization of Media Components for Production of Fibrinolytic
      Alkaline Metalloproteases from Xenorhabdus indica KB-3.
AB  - Xenorhabdus indica KB-3, a well-known protease producer, was isolated from its
      entomopathogenic nematode symbiont Steinernema thermophilum. Since medium
      constituents are critical to the protease production, the chemical components of
      the selected medium (soya casein digest broth) were optimized by rotatable
      central composite design (RCCD) using response surface methodology (RSM). The
      effects of all five chemical components (considered as independent variables),
      namely tryptone, soya peptone, dextrose, NaCl, and dipotassium phosphate, on
      protease production (dependent variable) were studied, and it was found that
      tryptone and dextrose had maximum influence on protease production. The protease
      production was increased significantly by 66.31% under optimal medium conditions
      (tryptone-5.71, soya peptone-4.9, dextrose-1.45, NaCl-6.08, and dipotassium
      phosphate-0.47 in g/L). To best of knowledge, there are no reports on
      optimization of medium component for protease production by X. indica KB-3 using
      RSM and their application in fibrinolysis. This study will be useful for
      industrial processes for production of protease enzyme from X. indica KB-3 for
      its application in the field of agriculture and medicine. 

PMID- 24864215
TI  - Cloning, Sequencing, and In Silico Analysis of beta-Propeller Phytase Bacillus
      licheniformis Strain PB-13.
AB  - beta -Propeller phytases (BPPhy) are widely distributed in nature and play a
      major role in phytate-phosphorus cycling. In the present study, a BPPhy gene from
      Bacillus licheniformis strain was expressed in E. coli with a phytase activity of
      1.15 U/mL and specific activity of 0.92 U/mg proteins. The expressed enzyme
      represented a full length ORF "PhyPB13" of 381 amino acid residues and differs by
      3 residues from the closest similar existing BPPhy sequences. The PhyPB13
      sequence was characterized in silico using various bioinformatic tools to better
      understand structural, functional, and evolutionary aspects of BPPhy class by
      multiple sequence alignment and homology search, phylogenetic tree construction,
      variation in biochemical features, and distribution of motifs and superfamilies.
      In all sequences, conserved sites were observed toward their N-terminus and C
      terminus. Cysteine was not present in the sequence. Overall, three major clusters
      were observed in phylogenetic tree with variation in biophysical characteristics.
      A total of 10 motifs were reported with motif "1" observed in all 44 protein
      sequences and might be used for diversity and expression analysis of BPPhy
      enzymes. This study revealed important sequence features of BPPhy and pave a way
      for determining catalytic mechanism and selection of phytase with desirable
      characteristics. 

PMID- 24864216
TI  - A rare case of acute renal failure secondary to rhabdomyolysis probably induced
      by donepezil.
AB  - Introduction. Acute renal failure (ARF) develops in 33% of the patients with
      rhabdomyolysis. The main etiologic factors are alcoholism, trauma, exercise
      overexertion, and drugs. In this report we present a rare case of ARF secondary
      to probably donepezil-induced rhabdomyolysis. Case Presentation. An 84-year-old
      male patient was admitted to the emergency department with a complaint of
      generalized weakness and reduced consciousness for two days. He had a history of
      Alzheimer's disease for one year and he had taken donepezil 5 mg daily for two
      months. The patient's physical examination revealed apathy, loss of cooperation,
      and decreased muscle strength. Laboratory studies revealed the following: urea:
      128 mg/dL; Creatinine 6.06 mg/dL; creatine kinase: 3613 mg/dL. Donepezil was
      discontinued and the patient's renal function tests improved gradually.
      Conclusion. Rhabdomyolysis-induced acute renal failure may develop secondary to
      donepezil therapy. 

PMID- 24864217
TI  - Extensive cortical diffusion restriction in a 50-year-old female with
      hyperammonemic encephalopathy and status epilepticus.
AB  - Comorbid hyperammonemic encephalopathy (HE) and status epilepticus (SE) leading
      to extensive cortical diffusion restriction (CDR) on MRI have not been previously
      reported. We describe a patient with HE who subsequently developed provoked SE.
      Sequential MRIs demonstrated a progressive CDR that involved the entire bilateral
      supratentorial cortex, thalami, and basal ganglia, resulting in death from
      cerebral edema and brain herniation. Diffuse CDR is most frequently seen after
      hypotension or hypoxia, which our patient did not experience. Such findings have
      also been described in both HE and SE (Milligan et al. (2009), Chatzikonstantinou
      et al. (2011), U-King-Im et al. (2011), and Bindu et al. (2009)), but not to the
      extent seen in our patient. Additionally, our patient had distinct radiologic
      features of both disease processes, suggesting a cumulative effect. The diagnosis
      of HE and SE in the setting of extensive CDR should not be missed and could lead
      to improved outcomes for two progressive, malignant, and treatable illnesses that
      can be easily overlooked. 

PMID- 24864219
TI  - Successful Same-Cycle Blastocyst Transfer following Laparoscopic Ovarian
      Detorsion: A Report of Two Cases and Literature Review.
AB  - Ovarian stimulation increases the risk of ovarian torsion. During an in vitro
      fertilization (IVF) cycle, the effects of ovarian torsion on retrieved oocytes
      and subsequent pregnancy chances are not clear. Moreover, no cases of ovarian
      torsion occurring following oocyte retrieval but prior to same-cycle embryo
      transfer have been reported. Such cases present a clinical dilemma with respect
      to optimal timing of embryo transfer. We report two cases of a 41-year-old and a
      32-year-old infertility patients undergoing IVF who were diagnosed with ovarian
      torsion within several days following oocyte retrieval. Both patients were
      treated by early laparoscopic evaluation and detorsion followed by day five
      embryo transfer, resulting in successful pregnancies. Therefore, after prompt
      laparoscopic ovarian untwisting of a torsed ovary following egg retrieval, embryo
      transfer may be performed as originally scheduled during the concurrent cycle
      leading to favorable pregnancy outcomes. 

PMID- 24864218
TI  - Extensive VZV Encephalomyelitis without Rash in an Elderly Man.
AB  - Introduction. Varicella zoster virus (VZV) encephalomyelitis with cranial nerve
      involvement is rare. Characteristically it is preceded by a rash and primarily
      presents in the immunocompromised. The spectrum of VZV neurologic disease is
      extensive and it is not uncommon to present without rash. We report the case of
      an elderly otherwise immunocompetent patient who presented with diverse
      manifestations of VZV CNS infection all occurring without rash. Case Report. A 78
      year-old man presented with 1 week of progressive paraparesis and sensory loss,
      malaise, and fevers. MRI of the neuraxis demonstrated numerous enhancing lesions:
      intramedullary, leptomeningeal, pachymeningeal, and cranial nerves. Cerebrospinal
      fluid (CSF) showed a white blood cell count of 420/ MU L with elevated protein
      (385 mg/dL). CSF VZV qualitative PCR was positive and CSF VZV immunofluorescence
      assay detected IgM antibody, confirming the diagnosis of VZV encephalomyelitis.
      Clinical and radiological improvement was observed after intravenous acyclovir
      treatment. Conclusion. This is a rare report of an immunocompetent patient with
      extensive VZV encephalomyelitis. We highlight the importance of considering this
      diagnosis even in the absence of the characteristic rash, and the potential risk
      of premature discontinuation of antiviral therapy once HSV has been excluded.
      Prompt recognition and treatment can dramatically reduce morbidity and mortality
      in patients. 

PMID- 24864220
TI  - A rare presentation of lymphoma of the cervix with cross-sectional imaging
      correlation.
AB  - Non-Hodgkin's lymphoma of the cervix is an extremely uncommon entity, with no
      standard established treatment protocol. A 43-year-old asymptomatic female with a
      history of dual hit blastic B-cell lymphoma/leukemia in complete remission
      presented with an incidental cervical mass, which was initially felt to represent
      a cervical fibroid on computed tomography (CT). It was further evaluated with
      ultrasound, biopsy, and positron emission tomography-computed tomography (PET
      CT), which demonstrated a growing biopsy-proven lymphomatous mass and new humeral
      head lesion. The patient was started on chemotherapy to control the newly
      diagnosed humeral head lesion, which then regressed. She then underwent radiation
      to the cervix with significant improvement in the cervical lymphoma. A review of
      cross-sectional imaging findings of lymphoma of the cervix is provided, including
      how to differentiate it from other more common diseases of the cervix. Clinical
      awareness of rare cervical masses such as lymphoma is very important in order to
      achieve timely diagnosis and appropriate treatment. 

PMID- 24864221
TI  - Hiatal hernia repair with gore bio-a tissue reinforcement: our experience.
AB  - Type I hiatal hernia is associated with gastroesophageal reflux disease (GERD) in
      50-90% of cases. Several trials strongly support surgery as an effective
      alternative to medical therapy. Today, laparoscopic fundoplication is considered
      as the procedure of choice. However, primary laparoscopic hiatal hernia repair is
      associated with upto 42% recurrence rate. Mesh reinforcement of the crural
      closure decreases the recurrence but can lead to complications, above all
      nonabsorbable ones. We experiment a new totally absorbable mesh by Gore. Case. We
      present a case of a 65-year-old female patient with a 6-year classic history of
      GERD. Endoscopy revealed a large hiatal hernia and esophagitis. pH study was
      positive for acid reflux; esophageal manometry revealed LES intrathoracic
      dislocation. With laparoscopic approach, the hiatal hernia defect was identified
      and primarily repaired, by crural closure. Gore Bio-A Tissue Reinforcement was
      trimmed to fit the defect accommodating the esophagus. Nissen fundoplication was
      performed. Result. Bio-A mesh was easily placed laparoscopically. It has good
      handling and could be cut and tailored intraoperatively for optimal adaptation.
      There were no short-term complications. Conclusion. Crural closure reinforcement
      can be done readily with this new totally absorbable mesh replaced by soft tissue
      over six months. However, further data and studies are needed to evaluate long
      term outcomes. 

PMID- 24864222
TI  - Autoinflation leading to failure of two-piece ambicor implantable penile
      prosthesis: an outcome from a methodical treatment of recalcitrant stuttering
      priapism.
AB  - Introduction. We present the case of a patient who received a two-piece Ambicor
      penile prosthesis for idiopathic recurrent "stuttering" priapism refractory to
      other treatment options. The patient returned unable to deflate the device due to
      an interesting anatomically induced mechanical failure. Aims. To describe the
      method and findings of this inflatable prosthesis failure. Results. Prosthesis
      failure occurred due to restrictive corporal diameter and the unique
      characteristics of fluid reservoir location in the two-piece inflatable
      prosthesis. The patient was successfully converted to a semirigid prosthesis with
      resolution of the pain that was due to his prosthesis autoinflation. Conclusion.
      Stuttering priapism remains a challenging clinical problem. Penile implantation
      is a reasonable long-term solution in a patient refractory to less invasive
      options. In patients with fibrotic corpora, a malleable device should be
      considered (at least temporarily) if unable to dilate comfortably to 13 mm. 

PMID- 24864223
TI  - Incidence of fractures after cardiac and lung transplantation: a single center
      experience.
AB  - Osteoporotic fractures are well-known complications of organ transplantation.
      Fracture rates up to 35% have been previously reported following heart and lung
      transplantations. Our institutional pretransplant protocols include DXA scans,
      vitamin D screening, and appropriate antiresorptive therapy. We aimed to assess
      the incidence of fragility fractures following cardiac or lung transplantation.
      In a retrospective study 210 electronic medical records of patients who underwent
      LT (110 men, 100 women) and 105 HT (88 men, 17 women) between 2005 and 2010 were
      analyzed. Both clinical and radiographic fractures were recorded. DXA scans were
      obtained immediately after transplant. 17 out of 210 LT patients (8.0%) had
      fractures after transplantation and 9 out of 105 HT patients (8.6%) had
      fractures. The median time to the first fracture was 12 months and the mean time
      was 18 months for both LT and HT. In the HT recipients, the median femoral neck T
      score was statistically lower in the fracture group versus the nonfracture group.
      Similar results were seen in the LT patients. Conclusion. Our findings
      demonstrate a much lower incidence of fractures in heart and lung transplant
      recipients in comparison with earlier reports. Comprehensive bone care and early
      initiation of antiresorptive therapy are possible contributors to these improved
      outcomes. 

PMID- 24864224
TI  - Effect of Three Colostrum Diets on Passive Transfer of Immunity and Preweaning
      Health in Calves on a California Dairy following Colostrum Management Training.
AB  - Following colostrum management training, a randomized field trial was conducted
      on a California dairy to determine the effect of supplementing pooled colostrum
      with either colostrum-derived replacer (CDR) or second-milking colostrum
      (transition milk) on failure of passive transfer (FPT) and preweaning morbidity
      risks. A total of 166 calves were randomly assigned to 4L first-milking pooled
      colostrum (treatment 1), 2L first-milking pooled colostrum and 2L of CDR
      (treatment 2), or 2L first-milking pooled colostrum and 2L second-milking pooled
      colostrum (treatment 3). Mean 24-hour serum TP and IgG for treatments 2 (TP 5.2
      g/dL, IgG 15.9 g/L) and 3 (TP 5.4 g/dL, IgG 18.3 g/L) did not statistically
      differ but were significantly lower than for treatment 1 (TP 5.9 g/dL, IgG 24.6
      g/L). Risk of FPT did not differ for treatments 1, 2, and 3 (0.0%, 9.3%, and
      1.9%, resp.). Similarly, the preweaning risk of diarrhea (81.0%, 92.5%, and
      87.0%, resp.) or pneumonia (6.9%, 13.2%, and 18.5%, resp.) did not differ between
      treatments. Feeding 4L first-milking pooled colostrum resulted in adequate
      passive transfer. When first-milking pooled colostrum quantity is inadequate, CDR
      or second-milking pooled colostrum can be used to supplement the required
      colostrum volume and IgG mass without adversely affecting the risks of FPT or
      preweaning diarrhea and pneumonia. 

PMID- 24864225
TI  - Understanding the added value of g-protein-coupled receptor heteromers.
AB  - G-protein-coupled receptors (GPCRs) constitute the most populated family of
      proteins within the human genome. Since the early sixties work on GPCRs and on
      GPCR-mediated signaling has led to a number of awards, the most recent being the
      Nobel Prize in Chemistry for 2012. The future of GPCRs research is surely based
      on their capacity for heteromerization. Receptor heteromers offer a series of
      challenges that will help in providing success in academic/basic research and
      translation into more effective and safer drugs. 

PMID- 24864226
TI  - Road rage: prevalence pattern and web based survey feasibility.
AB  - Introduction. Incidents of road rage are on a rise in India, but the literature
      is lacking in the aspect. There is an increasing realization of possibility of
      effective web based interventions to deliver public health related messages.
      Objective. The aim was to quantitatively evaluate risk factors among motor
      vehicle drivers using an internet based survey. Methods. Facebook users were
      evaluated using Life Orientation Test-Revised (LOT-R) and Driving Anger Scale
      (DAS). Results. An adequate response rate of 65.9% and satisfactory reliability
      with sizable correlation were obtained for both scales. Age was found to be
      positively correlated to LOT-R scores (r = 0.21; P = 0.02) and negatively
      correlated to DAS scores (r = -0.19; P = 0.03). Years of education were
      correlated to LOT-R scores (r = 0.26; P = 0.005) but not DAS scores (r = -0.14; P
      = 0.11). LOT-R scores did not correlate to DAS scores. Conclusion. There is high
      prevalence of anger amongst drivers in India particularly among younger males. A
      short web survey formatted in easy to use question language can result in a
      feasible conduction of an online survey. 

PMID- 24864227
TI  - Evaluation of anti-Candida activity of Vitis vinifera L. seed extracts obtained
      from wine and table cultivars.
AB  - For the first time, grape seed extracts (GSEs), obtained from wine and table
      cultivars of Vitis vinifera L., cultured in experimental fields of Lazio and
      Puglia regions of Italy and grown in different agronomic conditions, have been
      tested on 43 Candida species strains. We demonstrated a significant correlation
      between the content of the flavan-3-ols in GSEs extracts, with a polymerization
      degree >= 4, and anti-Candida activity. Moreover, we demonstrated that GSEs,
      obtained from plants cultured with reduced irrigation, showed a content of
      polymeric flavan-3-ols >250 mg/g with geometric mean MIC values between 5.7 and
      20.2 mg/L against Candida albicans reference strains. GSE, showing 573 mg/g of
      polymeric flavan-3-ols, has been tested in an experimental murine model of
      vaginal candidiasis by using noninvasive in vivo imaging technique. The results
      pointed out a significant inhibition of Candida albicans load 5 days after
      challenge. These findings indicate that GSEs with high content of polymeric
      flavan-3-ols can be used in mucosal infection as vaginal candidiasis.

PMID- 24864228
TI  - Human periodontal ligament derived progenitor cells: effect of STRO-1 cell
      sorting and Wnt3a treatment on cell behavior.
AB  - OBJECTIVES: STRO-1 positive periodontal ligament cells (PDLCs) and unsorted PDLCs
      have demonstrated potential for periodontal regeneration, but the comparison
      between unsorted cells and the expanded STRO-1 sorted cells has never been
      reported. Additionally, Wnt3a is involved in cell proliferation thus may benefit
      in vitro PDLC expansion. The aim was to evaluate the effect of STRO-1 cell
      sorting and Wnt3a treatment on cell behavior of human PDLCs (hPDLCs). MATERIALS
      AND METHODS: STRO-1 positive hPDLCs were sorted and the sorted cells were
      expanded and compared with their unsorted parental cells. Thereafter, hPDLCs were
      treated with or without Wnt3a and the cell proliferation, self-renewal, and
      osteogenic differentiation were evaluated. RESULTS: No differences were measured
      between the expanded STRO-1-sorted cells and unsorted parental cells in terms of
      proliferation, CFU, and mineralization capacity. Wnt3a enhanced the proliferation
      and self-renewal ability of hPDLCs significantly as displayed by higher DNA
      content values, a shorter cell population doubling time, and higher expression of
      the self-renewal gene Oct4. Moreover, Wnt3a promoted the expansion of hPDLCs for
      5 passages without affecting cell proliferation, CFU, and osteogenic capacity.
      CONCLUSIONS: Expanded STRO-1-sorted hPDLCs showed no superiority compared to
      their unsorted parental cells. On the other hand, Wnt3a promotes the efficient
      hPDLC expansion and retains the self-renewal and osteogenic differentiation
      capacity.

PMID- 24864229
TI  - Diverse effects of ANXA7 and p53 on LNCaP prostate cancer cells are associated
      with regulation of SGK1 transcription and phosphorylation of the SGK1 target
      FOXO3A.
AB  - Tumor suppressor function of the calcium/phospholipid-binding Annexin-A7 (ANXA7)
      has been shown in Anxa7-deficient mice and validated in human cancers. In the
      androgen-resistant prostate cancer cells, ANXA7 and p53 showed similar
      cytotoxicity levels. However, in the androgen-sensitive LNCaP, ANXA7 greatly
      exceeded the p53-induced cytotoxicity. We hypothesized that the p53
      underperformance in LNCaP could be due to the involvement of p53-responsive SGK1
      and FOXO3A. In this study, we show that p53 failed to match programmed cell death
      (PCD) and G1-arrest that were induced by ANXA7 in LNCaP. WT-ANXA7 preserved total
      FOXO3A expression with no hyperphosphorylation that could enable FOXO3A nuclear
      translocation and proapoptotic transcription. In contrast, in the p53-transfected
      LNCaP cells with maintained cell proliferation, the phosphorylated (but not
      total) FOXO3A fraction was increased implying a predominantly cytoplasmic
      localization and, subsequently, a lack of FOXO3A proapoptotic transcription. In
      addition, p53 reduced the expression of aberrant SGK1 protein form in LNCaP.
      Using Ingenuity Pathway Analysis and p53-signature genes, we elucidated the role
      of distinct SGK1/FOXO3A-associated regulation in p53 versus ANXA7 responses and
      proposed that aberrant SGK1 could affect reciprocal SGK1-FOXO3A-Akt regulation.
      Thus, the failure of the cell growth regulator p53 versus the phospholipid
      binding ANXA7 could be potentially attributed to its diverse effects on SGK1
      FOXO3A-Akt pathway in the PTEN-deficient LNCaP. 

PMID- 24864230
TI  - Syn-lethality: an integrative knowledge base of synthetic lethality towards
      discovery of selective anticancer therapies.
AB  - Synthetic lethality (SL) is a novel strategy for anticancer therapies, whereby
      mutations of two genes will kill a cell but mutation of a single gene will not.
      Therefore, a cancer-specific mutation combined with a drug-induced mutation, if
      they have SL interactions, will selectively kill cancer cells. While numerous SL
      interactions have been identified in yeast, only a few have been known in human.
      There is a pressing need to systematically discover and understand SL
      interactions specific to human cancer. In this paper, we present Syn-Lethality,
      the first integrative knowledge base of SL that is dedicated to human cancer. It
      integrates experimentally discovered and verified human SL gene pairs into a
      network, associated with annotations of gene function, pathway, and molecular
      mechanisms. It also includes yeast SL genes from high-throughput screenings which
      are mapped to orthologous human genes. Such an integrative knowledge base,
      organized as a relational database with user interface for searching and network
      visualization, will greatly expedite the discovery of novel anticancer drug
      targets based on synthetic lethality interactions. The database can be downloaded
      as a stand-alone Java application. 

PMID- 24864232
TI  - Biotechnology in environmental monitoring and pollution abatement.

PMID- 24864231
TI  - Time-lapse dynamics of the mouse oocyte chromatin organisation during meiotic
      resumption.
AB  - In the mammalian oocyte, distinct patterns of centromeres and pericentromeric
      heterochromatin localisation correlate with the gamete's developmental
      competence. Mouse antral oocytes display two main types of chromatin
      organisation: SN oocytes, with a ring of Hoechst-positive chromatin surrounding
      the nucleolus, and NSN oocytes lacking this ring. When matured to MII and
      fertilised, only SN oocytes develop beyond the 2-cell, and reach full term. To
      give detailed information on the dynamics of the SN or NSN chromatin during
      meiosis resumption, we performed a 9 hr time-lapse observation. The main
      significant differences recorded are: (1) reduction of the nuclear area only in
      SN oocytes; (2) ~17 min delay of GVBD in NSN oocytes; (3) chromatin condensation,
      after GVBD, in SN oocytes; (4) formation of 4-5 CHCs in SN oocytes; (5) increase
      of the perivitelline space, ~57 min later in NSN oocytes; (6) formation of a
      rosette-like disposition of CHCs, ~84 min later in SN oocytes; (7) appearance of
      the MI plate ~40 min later in NSN oocytes. Overall, we described a pathway of
      transition from the GV to the MII stage that is punctuated of discrete recordable
      events showing their specificity and occurring with different time kinetics in
      the two types of oocytes.

PMID- 24864234
TI  - Oxidative stress indicators in patients with prostate disorders in Enugu, South
      East Nigeria.
AB  - Depletion of cellular antioxidants can result from free radical formation due to
      normal endogenous reactions and the ingestion of exogenous substances and
      environmental factors. The levels of reactive oxygen species-(ROS-) scavenging
      enzymes such as SOD and glutathione peroxidase have been shown to be
      significantly altered in malignant cells and in primary cancer tissues. The aim
      of this study was to determine the antioxidant status of patients with prostate
      disorders in South-East Nigeria to ascertain the possible role of depletion of
      antioxidants in prostatic degeneration. 104 subjects made up of 40 PCa patients,
      32 with BPH, and 32 controls participated in this study. The levels of superoxide
      dismutase, glutathione peroxidase, vitamin C, and vitamin E were estimated using
      standard procedures. The results show that both the BPH and PCa patients had a
      significant decrease (P < 0.05) in GPX, SOD, vitamin C, and vitamin E levels
      compared to the control subjects. However, there was also a significant decrease
      (P < 0.05) in SOD and vitamin C levels in PCa patients when compared with the BPH
      group. This indicates that patients with BPH and prostate cancer have decreased
      antioxidant status and may benefit from micronutrient supplementation. 

PMID- 24864233
TI  - High level of Tregs is a positive prognostic marker in patients with HPV-positive
      oral and oropharyngeal squamous cell carcinomas.
AB  - BACKGROUND: Human papillomaviruses (HPVs) have been proved as one of the
      etiological factors of oropharyngeal squamous cell carcinoma (OPSCC). Patients
      with tumors of viral etiology have a lower recurrence rate and better prognosis.
      OPSCC is linked to an alteration in the immune system. Only a limited number of
      studies have correlated both the immunological parameters and HPV status with
      patient prognosis. The aim of this study was to determine whether HPV infection
      and the immunological status influence patient prognosis individually or in
      concurrence. MATERIAL AND METHODS: Sixty patients with oral and oropharyngeal
      carcinomas were enrolled. They were divided into HPV-positive and HPV-negative
      groups based on the expression of HPV 16 E6 mRNA. Basic lymphocyte subpopulations
      were determined in the peripheral blood by means of flow cytometry. RESULTS:
      Significantly better disease-specific survival (DSS) was observed in patients
      with HPV-positive tumors. Nodal status, tumor grade, recurrence, and CD8+/Tregs
      ratio were identified as factors influencing DSS. A higher level of Tregs and a
      lower ratio of CD8/Tregs influenced overall survival (OS) independently of HPV
      status and age. Patients with HPV-positive tumors and high levels of Tregs
      survived significantly better than patients from the other groups. CONCLUSION:
      Better survival is associated with HPV positivity and elevated Tregs levels. Our
      data suggest that HPV infection and Tregs do not influence patient prognosis in
      concurrence.

PMID- 24864235
TI  - Effects of canonical NF-kappaB signaling pathway on the proliferation and
      odonto/osteogenic differentiation of human stem cells from apical papilla.
AB  - BACKGROUND INFORMATION: NF-kappaB signaling pathway plays a complicated role in
      the biological functions of mesenchymal stem cells. However, the effects of NF
      kappaB pathway on the odonto/osteogenic differentiation of stem cells from apical
      papilla (SCAPs) remain unclear. The present study was designed to evaluate the
      effects of canonical NF-kappaB pathway on the osteo/odontogenic capacity of SCAPs
      in vitro. RESULTS: Western blot results demonstrated that NF-kappaB pathway in
      SCAPs was successfully activated by TNF-alpha or blocked by BMS-345541. NF-kappaB
      pathway-activated SCAPs presented a higher proliferation activity compared with
      control groups, as indicated by dimethyl-thiazol-diphenyl tetrazolium bromide
      assay (MTT) and flow cytometry assay (FCM). Wound scratch assay revealed that NF
      kappaB pathway-activated SCAPs presented an improved migration capacity, enhanced
      alkaline phosphatase (ALP) activity, and upregulated mineralization capacity of
      SCAPs, as compared with control groups. Meanwhile, the odonto/osteogenic markers
      (ALP/ALP, RUNX2/RUNX2, OSX/OSX, OCN/OCN, OPN/OPN, BSP/BSP, DSPP/DSP, and DMP
      1/DMP-1) in NF-kappaB pathway-activated SCAPs were also significantly upregulated
      as compared with control groups at both protein and mRNA levels. However, NF
      kappaB pathway-inhibited SCAPs exhibited a lower proliferation/migration
      capacity, and decreased odonto/osteogenic ability in comparison with control
      groups. CONCLUSION: Our findings suggest that classical NF-kappaB pathway plays a
      paramount role in the proliferation and committed differentiation of SCAPs.

PMID- 24864236
TI  - Novel design strategy for checkpoint kinase 2 inhibitors using pharmacophore
      modeling, combinatorial fusion, and virtual screening.
AB  - Checkpoint kinase 2 (Chk2) has a great effect on DNA-damage and plays an
      important role in response to DNA double-strand breaks and related lesions. In
      this study, we will concentrate on Chk2 and the purpose is to find the potential
      inhibitors by the pharmacophore hypotheses (PhModels), combinatorial fusion, and
      virtual screening techniques. Applying combinatorial fusion into PhModels and
      virtual screening techniques is a novel design strategy for drug design. We used
      combinatorial fusion to analyze the prediction results and then obtained the best
      correlation coefficient of the testing set (r test) with the value 0.816 by
      combining the Best(train)Best(test) and Fast(train)Fast(test) prediction results.
      The potential inhibitors were selected from NCI database by screening according
      to Best(train)Best(test) + Fast(train)Fast(test) prediction results and molecular
      docking with CDOCKER docking program. Finally, the selected compounds have high
      interaction energy between a ligand and a receptor. Through these approaches, 23
      potential inhibitors for Chk2 are retrieved for further study.

PMID- 24864237
TI  - Biodegradation and utilization of organophosphorus pesticide malathion by
      Cyanobacteria.
AB  - Three strains of filamentous Cyanobacteria were used to study their growth and
      utilization of organophosphorus pesticide malathion. A sharp decrease in the
      growth of the algal strains was observed by increasing the concentration of
      malathion. Amongst them Nostoc muscorum tolerated different concentrations and
      was recorded as the highest efficient strain for biodegradation (91%) of this
      compound. Moreover, carbohydrate and protein content of their cells overtopped
      the other strains especially at higher concentrations. The algal strains were
      further subjected to grow under P-limitation in absence and presence of
      malathion. Although, the algal growth under P-limitation recorded a very poor
      level, a massive enhanced growth and phosphorous content of cells were obtained
      when the P-limited medium was amended with malathion. This study clarified that
      N. muscorum with its capability to utilize malathion as a sole phosphorous source
      is considered as an inexpensive and efficient biotechnology for remediation of
      organophosphorus pesticide from contaminated wastewater. 

PMID- 24864238
TI  - Predicting Mycobacterium tuberculosis complex clades using knowledge-based
      Bayesian networks.
AB  - We develop a novel approach for incorporating expert rules into Bayesian networks
      for classification of Mycobacterium tuberculosis complex (MTBC) clades. The
      proposed knowledge-based Bayesian network (KBBN) treats sets of expert rules as
      prior distributions on the classes. Unlike prior knowledge-based support vector
      machine approaches which require rules expressed as polyhedral sets, KBBN
      directly incorporates the rules without any modification. KBBN uses data to
      refine rule-based classifiers when the rule set is incomplete or ambiguous. We
      develop a predictive KBBN model for 69 MTBC clades found in the SITVIT
      international collection. We validate the approach using two testbeds that model
      knowledge of the MTBC obtained from two different experts and large DNA
      fingerprint databases to predict MTBC genetic clades and sublineages. These
      models represent strains of MTBC using high-throughput biomarkers called spacer
      oligonucleotide types (spoligotypes), since these are routinely gathered from
      MTBC isolates of tuberculosis (TB) patients. Results show that incorporating
      rules into problems can drastically increase classification accuracy if data
      alone are insufficient. The SITVIT KBBN is publicly available for use on the
      World Wide Web. 

PMID- 24864239
TI  - Tissue biomarkers in prognostication of serous ovarian cancer following
      neoadjuvant chemotherapy.
AB  - Serous ovarian cancer (SOC) is a significant cause of morbidity and mortality in
      females with poor prognosis because of advanced stage at presentation. Recently,
      neoadjuvant chemotherapy (NACT) is being used for management of advanced SOC, but
      role of tissue biomarkers in prognostication following NACT is not well
      established. The study was conducted on advanced stage SOC patients (n = 100)
      that were treated either conventionally (n = 50) or with NACT (n = 50), followed
      by surgery. In order to evaluate the expression of tissue biomarkers (p53, MIB1,
      estrogen and progesterone receptors, Her-2/neu, E-cadherin, and Bcl2),
      immunohistochemistry and semiquantitative scoring were done following
      morphological examination. Following NACT, significant differences in tumor
      histomorphology were observed as compared to the native neoplasms. MIB 1 was
      significantly lower in cases treated with NACT and survival outcome was
      significantly better in cases with low MIB 1. ER expression was associated with
      poor overall survival. No other marker displayed any significant difference in
      expression or correlation with survival between the two groups. Immunophenotype
      of SOC does not differ significantly in samples from cases treated with NACT,
      compared to upfront surgically treated cases. The proliferating capacity of the
      residual tumor cells is less, depicted by low mean MIB1 LI. MIB 1 and ER
      inversely correlate with survival. 

PMID- 24864240
TI  - Microarray analysis of serum mRNA in patients with head and neck squamous cell
      carcinoma at whole-genome scale.
AB  - With the increasing demand for noninvasive approaches in monitoring head and neck
      cancer, circulating nucleic acids have been shown to be a promising tool. We
      focused on the global transcriptome of serum samples of head and neck squamous
      cell carcinoma (HNSCC) patients in comparison with healthy individuals. We
      compared gene expression patterns of 36 samples. Twenty-four participants
      including 16 HNSCC patients (from 12 patients we obtained blood samples 1 year
      posttreatment) and 8 control subjects were recruited. The Illumina HumanWG-6 v3
      Expression BeadChip was used to profile and identify the differences in serum
      mRNA transcriptomes. We found 159 genes to be significantly changed (Storey's P
      value <0.05) between normal and cancer serum specimens regardless of factors
      including p53 and B-cell lymphoma family members (Bcl-2, Bcl-XL). In contrast,
      there was no difference in gene expression between samples obtained before and
      after surgery in cancer patients. We suggest that microarray analysis of serum
      cRNA in patients with HNSCC should be suitable for refinement of early stage
      diagnosis of disease that can be important for development of new personalized
      strategies in diagnosis and treatment of tumours but is not suitable for
      monitoring further development of disease. 

PMID- 24864242
TI  - Immunohistochemical detection of cancer stem cell related markers CD44 and CD133
      in metastatic colorectal cancer patients.
AB  - AIM: The goal of this study was to semiquantitatively detect presence of cancer
      stem cells markers CD44 and CD133 in immunohistochemically stained paired samples
      of colorectal cancer (CRC) and colorectal liver metastases (CLM). Level of
      staining intensity was compared to clinical and pathological characteristics of
      tumors with the aim to identify impact of CD44 or CD133 expression on tumor
      behavior. PATIENTS AND METHODS: Formalin fixed paraffin embedded samples from 94
      patients with colorectal tumor and liver metastases were collected at Sikl's
      Department of Pathology. Samples were stained by antibodies against CD44 and
      CD133. Presence and intensity of staining was assessed semiquantitatively by
      three trained researchers. RESULTS: Patients with higher level of CD133 staining
      in CRC had longer disease free interval (Cox-Mantel P = 0.0244), whereas we found
      no relation between CD44 expression and overall survival or disease free
      interval. CD133 expression in CRC and CLM differed based on CRC grading; in case
      of CD44 we found differences in staining intensity in individual stages of tumor
      lymph node invasion. CONCLUSION: Effect of cancer stem cell markers on prognosis
      of colorectal cancer can vary depending on pathological classification of tumor,
      and we have shown that CD133, generally considered to be a negative marker, can
      bear also clinically positive prognostic information in group of patients with
      colorectal liver metastases.

PMID- 24864241
TI  - Leczyme: a new candidate drug for cancer therapy.
AB  - Sialic acid-binding lectin (SBL), isolated from oocytes of Rana catesbeiana, is
      leczyme and has both lectin and ribonuclease (RNase) activities. A remarkable
      antitumor effect of SBL has also been reported. SBL agglutinates various kinds of
      tumor cells but not normal cells. SBL agglutination activity is not affected by
      mono- or oligosaccharides. However, SBL-induced agglutination and antitumor
      effects are inhibited by sialomucin but not asialomucin. In addition, SBL has
      very little effect on sialidase-treated cells. SBL causes cancer-selective
      induction of apoptosis by multiple signaling pathways, which target RNA.
      Synergistic antitumor effects with other molecules, such as tumor necrosis factor
      related apoptosis ligand (TRAIL) and interferon- gamma (IFN-gamma), have been
      reported. Thus, SBL may be a novel candidate molecule for anticancer drug
      development. Sialoglycoconjugates on the tumor cell surface may be associated
      with lectin activity and antitumor effects of SBL. We review the properties of
      SBL, particularly its lectin, RNase, and antitumor activities, and
      comprehensively examine the potential application of SBL for clinical purposes.

PMID- 24864243
TI  - Experimental measurements for the effect of dilution procedure in blood esterases
      as animals biomarker for exposure to OP compounds.
AB  - Organophosphate compounds can bind to carboxylesterase, which may lower the
      concentration of organophosphate pesticides at the target site enzyme,
      cholinesterase. It is unclear from the literature whether it is the
      carboxylesterase affinity for the organophosphate and/or the number of
      carboxylesterase molecules that is the dominant factor in determining the
      protective potential of carboxylesterase. The fundamental dilutions and kinetic
      effects of esterase enzyme are still poorly understood. This study aims to
      confirm and extend our current knowledge about the effects of dilutions on
      esterases activities in the blood for birds with respect to protecting the enzyme
      from organophosphate inhibition. There was significantly higher esterases
      activities in dilution 1 : 10 in the all blood samples from quail, duck, and
      chick compared to other dilutions (1 : 5, 1 : 15, 1 : 20, and 1 : 25) in all
      cases. Furthermore, our results also pointed to the importance of estimating
      different dilutions effects prior to using in birds as biomarker tools of
      environmental exposure. Concentration-inhibition curves were determined for the
      inhibitor in the presence of dilutions 1 : 5, 1 : 10, plus 1 : 15 (to stimulate
      carboxylesterase). Point estimates (concentrations calculated to produce 20, 50,
      and 80% inhibition) were compared across conditions and served as a measure of
      esterase-mediated detoxification. Results with well-known inhibitors (malathion)
      were in agreement with the literature, serving to support the use of this assay.
      Among the thiol-esters dilution 1 : 5 was observed to have the highest
      specificity constant (k(cat)/K(m)), and the K m and k cat values were 176 MUM and
      16,765 s(-1), respectively, for S-phenyl thioacetate ester, while detected in
      dilution 1: 15 was the lowest specificity constant (k(cat)/K(m)), and the Km and
      k cat values were 943 MUM and 1154 s(-1), respectively, for acetylthiocholine
      iodide ester.

PMID- 24864244
TI  - Biological evaluation of 131I- and CF750-labeled Dmab(scFv)-Fc antibodies for
      xenograft imaging of CD25-positive tumors.
AB  - A Dmab(scFv)-Fc antibody containing the single chain variable fragment of a
      humanized daclizumab antibody and the Fc fragment of a human IgG1 antibody was
      produced via recombinant expression in Pichia pastoris. The Dmab(scFv)-Fc
      antibody forms a dimer in solution, and it specifically binds CD25-positive tumor
      cells and tumor tissues. For tumor imaging, the Dmab(scFv)-Fc antibody was
      labeled with the 131I isotope and CF750 fluorescent dye, respectively. After
      intravenous injection of mice bearing CD25-positive tumor xenografts, tumor
      uptake of the (131)I-Dmab(scFv)-Fc antibody was visible at 1 h, and clear images
      were obtained at 5 h using SPECT/CT. After systemic administration of the CF750
      Dmab(scFv)-Fc antibody, tumor uptake was present as early as 1 h, and tumor
      xenografts could be kinetically imaged within 9 h after injection. These results
      indicate that the Dmab(scFv)-Fc antibody rapidly and specifically targets CD25
      positive tumor cells, suggesting the potential of this antibody as an imaging
      agent for the diagnosis of lymphomatous-type ATLL.

PMID- 24864245
TI  - Synthesis and evaluation of tetramethylguanidinium-polyethylenimine polymers as
      efficient gene delivery vectors.
AB  - Previously, we demonstrated that 6-(N,N,N',N'-tetramethylguanidinium chloride)
      hexanoyl-polyethylenimine (THP) polymers exhibited significantly enhanced
      transfection efficiency and cell viability. Here, in the present study, we have
      synthesized a series of N,N,N',N'-tetramethylguanidinium-polyethylenimine (TP1
      TP5) polymers via a single-step reaction involving peripheral primary amines of
      bPEI and varying amounts of 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium
      hexafluorophosphate (HBTU). These polymers were found to interact efficiently
      with negatively charged pDNA and formed stable complexes in the size range of
      ~240-450 nm. Acid-base titration profiles revealed improved buffering capacity of
      TP polymers as compared to bPEI. Transfection and cytotoxicity assays performed
      with TP/pDNA complexes on HEK293, CHO, and HeLa cells showed significantly higher
      transfection efficiency and cell viability with one of the complexes, TP2/pDNA
      complex, exhibited the highest transfection efficiency (~1.4-2.3-fold)
      outcompeting native bPEI and the commercially available transfection reagent,
      Lipofectamine 2000. Compared to previously reported THP polymers, the
      transfection efficiency of TP/pDNA complexes was found to be lower, as examined
      by flow cytometry. These results highlight the importance of the hydrophobic C-6
      linker in THP polymers in forming compact nanostructures with pDNA, which might
      lead to efficient uptake and internalization of the complexes; however, the
      projected TP polymers offer an advantage of their rapid and economical one-step
      synthesis.

PMID- 24864246
TI  - Does long-term use of silver nanoparticles have persistent inhibitory effect on
      H. pylori based on Mongolian gerbil's model?
AB  - BACKGROUND: It is urgent to find alternative agents due to increasing failure
      rate of Helicobacter pylori (H. pylori) eradication. The study surveyed the long
      term effect of silver nanoparticles (AgNP) on H. pylori based on Mongolian
      gerbil's model. MATERIALS AND METHODS: Fifty gerbils were randomly allocated to
      six groups (A-F). Group (Gr) A: the gerbils were fed with broth; Gr B and D: the
      gerbils were fed with AgNP/clay complex (0.1% of weight); Gr C and E: the gerbils
      were fed with AgNP/clay complex(1% of weight); and Gr D, E, and F: the gerbils
      were inoculated with H. pylori. At the 20th experimental week, the gerbils were
      sacrificed. Histology was evaluated according to the classification of the Sydney
      system. P < 0.05 was considered to be statistically significant. RESULTS: The
      AgNP/clay has more obvious inhibitory effect on H. pylori in vitro. There was a
      trend of higher concentrations of AgNP with stronger inhibitory effect on H.
      pylori growth (P = 0.071). There were no significant differences of inflammation
      among groups D, E, and F (P = 0.688). CONCLUSION: AgNP/clay would be a potential
      and safe agent for inhibiting H. pylori. It should be helpful for eradication of
      H. pylori infection.

PMID- 24864248
TI  - Image-guided hypofractionated radiotherapy in low-risk prostate cancer patients.
AB  - AIM: To evaluate efficacy and toxicity of image-guided hypofractionated
      radiotherapy (HFRT) in the treatment of low-risk prostate cancer. Outcomes and
      toxicities of this series of patients were compared to another group of 32 low
      risk patients treated with conventional fractionation (CFRT). METHODS: Fifty-nine
      patients with low-risk prostate cancer were analysed. Total dose for the prostate
      and proximal seminal vesicles was 60 Gy delivered in 20 fractions. RESULTS: The
      median follow-up was 30 months. The actuarial 4-year overall survival,
      biochemical free survival, and disease specific survival were 100%, 97.4%, and
      97.4%, respectively. Acute grade 1-2 gastrointestinal (GI) and genitourinary (GU)
      toxicity rates were 11.9% and 40.7%, respectively. Grade 1 GI and GU late
      toxicity rates were 8.5% and 13.6%, respectively. No grade >= 2 late toxicities
      were recorded. Acute grade 2-3 GU toxicity resulted significantly lower (P =
      0.04) in HFRT group compared to the CFRT group. The cumulative 4-year incidence
      of grade 1-2 GU toxicity was significantly higher (P < 0.001) for HFRT patients.
      CONCLUSIONS: Our study demonstrated that hypofractionated regimen provided
      excellent biochemical control in favorable risk prostate cancer patients. The
      incidence of GI and GU toxicity was low. However, HFRT presented higher
      cumulative incidence of low-grade late GU toxicity than CFRT.

PMID- 24864247
TI  - Hyperglycemia, a neglected factor during cancer progression.
AB  - Recent evidence from large cohort studies suggests that there exists a higher
      cancer incidence in people with type 2 diabetes (DM2). However, to date, the
      potential reasons for this association remain unclear. Hyperglycemia, the most
      important feature of diabetes, may be responsible for the excess glucose supply
      for these glucose-hungry cells, and it contributes to apoptosis resistance,
      oncogenesis, and tumor cell resistance to chemotherapy. Considering associations
      between diabetes and malignancies, the effect of hyperglycemia on cancer
      progression in cancer patients with abnormal blood glucose should not be
      neglected. In this paper, we describe the role that hyperglycemia plays in cancer
      progression and treatment and illustrate that hyperglycemia may contribute to a
      more malignant phenotype of cancer cells and lead to drug resistance. Therefore,
      controlling hyperglycemia may have important therapeutic implications in cancer
      patients. 

PMID- 24864249
TI  - Endocannabinoid receptors gene expression in morbidly obese women with
      nonalcoholic fatty liver disease.
AB  - BACKGROUND: Recent reports suggest a role for the endocannabinoid system in the
      pathology of nonalcoholic fatty liver disease (NAFLD). The aim of this study was
      to investigate the relationship between liver expression of cannabinoid (CB)
      receptor subtypes, CB1 and CB2, in morbidly obese (MO) women with different
      histological stages of NAFLD. METHODS: We analysed hepatic CB1 and CB2 mRNA
      expression, and the expression of genes involved in lipid metabolism in 72 MO
      women, subclassified by liver histology into MO with normal liver (NL, n = 16),
      simple steatosis (SS, n = 28), and nonalcoholic steatohepatitis (NASH, n = 28) by
      enzyme-linked immunosorbent assay and RT-PCR. RESULTS: We found that CB1 mRNA
      expression was significantly higher in NASH compared with SS and correlated
      negatively with PPARalpha. Regarding CB2, CB2 mRNA expression correlated
      positively with ACC1, PPARgamma, IL6, TNFalpha, resistin, and adiponectin.
      CONCLUSIONS: The increased expression of CB1 in NASH and the negative correlation
      with PPARalpha suggest a deleterious role of CB1 in NAFLD. Regarding CB2, its
      positive correlation with the anti-inflammatory molecule adiponectin and,
      paradoxically, with inflammatory genes suggests that this receptor has a dual
      role. Taken together, our results suggest that endocannabinoid receptors might be
      involved in the pathogenesis of NAFLD, a finding which justifies further study.

PMID- 24864250
TI  - The association between autoantibodies and peripheral neuropathy in lupus
      nephritis.
AB  - BACKGROUND AND AIM: The sensitivity and specificity of biomarkers used for
      predicting peripheral neuropathy in patients with systemic lupus erythematosus
      (SLE) and nephritis (SLE-LN) remain unsatisfactory. This study aimed to determine
      the autoantibodies levels in SLE-LN patients with peripheral neuropathy. METHODS:
      Data of 559 SLE-LN patients were collected retrospectively, including titers of
      autoantibodies, electrodiagnostic studies, and clinical manifestations. RESULTS:
      The neurologic manifestations of the SLE-LN patients were diverse and
      nonspecific. The prevalence rate of peripheral polyneuropathy was 2.68%, of which
      about 73.33% was mixed sensory-motor polyneuropathy. Numbness and functional
      gastrointestinal problems were the most prevalent symptoms and these were noted
      in every subtype of peripheral neuropathy. Among all the serology markers, anti
      Ro was significantly associated with neuropathy related to SLE (P = 0.009).
      CONCLUSION: Peripheral neuropathy among LN patients is rare and may be easily
      overlooked. This study demonstrated that positive anti-Ro antibody may imply
      neuropathy in LN patients. Thus, anti-Ro can be considered a biomarker that
      should be added to the panel of conventional autoantibodies in LN patients.

PMID- 24864251
TI  - rs744166 polymorphism of the STAT3 gene is associated with risk of gastric cancer
      in a Chinese population.
AB  - The aim of this study was to explore the association between polymorphisms in
      signal transducer and activator of transcription protein 3 (STAT3) and the risk
      of gastric cancer. In the present study, a case-control study was conducted in
      which rs2293152 and rs744166 polymorphisms in STAT3 were analyzed in 209 Chinese
      patients with gastric cancer and 294 cancer-free controls. The genotypes were
      determined by polymerase chain reaction restriction fragment length polymorphism
      method. For the rs744166 polymorphism, the TC genotype (adjusted OR = 0.60, 95%
      CI = 0.39-0.92, and P = 0.020) and CC genotype (adjusted OR = 0.41, 95% CI = 0.21
      0.80, and P = 0.009) were associated with a decreased risk of gastric cancer
      compared to the TT genotype. However, rs2293152 did not show any difference in
      gastric cancer risk between patients and controls in the CG/CC genotype compared
      to the GG genotype. Besides, the SNP effects were additive to the effects of
      environmental factors without any interaction between them in the susceptibility
      to gastric cancer. Collectively, rs744166 polymorphism might be significantly
      associated with a decreased risk of gastric cancer in a Chinese population.
      Additionally, polymorphisms in STAT3, along with environmental factors, might be
      associated with the development of gastric cancer. 

PMID- 24864252
TI  - Building and repairing the heart: what can we learn from embryonic development?
AB  - Mammalian heart formation is a complex morphogenetic event that depends on the
      correct temporal and spatial contribution of distinct cell sources. During
      cardiac formation, cellular specification, differentiation, and rearrangement are
      tightly regulated by an intricate signaling network. Over the last years, many
      aspects of this network have been uncovered not only due to advances in cardiac
      development comprehension but also due to the use of embryonic stem cells (ESCs)
      in vitro model system. Additionally, several of these pathways have been shown to
      be functional or reactivated in the setting of cardiac disease. Knowledge
      withdrawn from studying heart development, ESCs differentiation, and cardiac
      pathophysiology may be helpful to envisage new strategies for improved cardiac
      repair/regeneration. In this review, we provide a comparative synopsis of the
      major signaling pathways required for cardiac lineage commitment in the embryo
      and murine ESCs. The involvement and possible reactivation of these pathways
      following heart injury and their role in tissue recovery will also be discussed. 

PMID- 24864253
TI  - Topical application of Cleome viscosa increases the expression of basic
      fibroblast growth factor and type III collagen in rat cutaneous wound.
AB  - Cleome viscosa L. (Cleomaceae) is an important traditional medicine of the Indian
      Ayurvedic and Chinese-medicine system documented for rheumatic arthritis,
      hypertension, malaria, neurasthenia, and wound healing. The plant is also known
      as Asian spider flower and is distributed throughout the greater part of India.
      The present study explored the wound healing property of C. viscosa methanol
      extract (CvME) and its related mechanism using Wistar rat cutaneous excision
      wound model. Wound contraction rate, hydroxyproline quantification, and
      histopathological examination of wound granulation tissue were performed. The
      healing potential was comparatively assessed with a reference gentamicin sulfate
      hydrogel (0.01% w/w). Western blot for COL3A1, bFGF, and Smad-2, Smad-3, Smad-4,
      and Smad-7 was performed with 7-day postoperative granulation tissue. Results
      revealed that the topical application of CvME (2.5% w/w) significantly
      accelerated the wound contraction rate (95.14%, 24 postoperative days), increased
      the hydroxyproline content (3.947 mg/100 mg tissue), and improved histopathology
      of wound tissue as compared to control groups. Western blot analysis revealed
      that CvME significantly upregulated the expression of COL3A1 and bFGF and
      increased the Smad-mediated collagen production in granulation tissue. These
      findings suggest that C. viscosa promoted the wound repair process by attenuating
      the Smad-mediated collagen production in wound granulation tissue.

PMID- 24864254
TI  - The interaction pattern between a homology model of 40S ribosomal S9 protein of
      Rhizoctonia solani and 1-hydroxyphenaize by docking study.
AB  - 1-Hydroxyphenazine (1-OH-PHZ), a natural product from Pseudomonas aeruginosa
      strain SD12, was earlier reported to have potent antifungal activity against
      Rhizoctonia solani. In the present work, the antifungal activity of 1-OH-PHZ on
      40S ribosomal S9 protein was validated by molecular docking approach. 1-OH-PHZ
      showed interaction with two polar contacts with residues, Arg69 and Phe19, which
      inhibits the synthesis of fungal protein. Our study reveals that 1-OH-PHZ can be
      a potent inhibitor of 40S ribosomal S9 protein of R. solani that may be a
      promising approach for the management of fungal diseases. 

PMID- 24864255
TI  - The multiple silicone tube device, "tubes within a tube," for multiplication in
      nerve reconstruction.
AB  - Multiple nerve branches were created during the regeneration procedure after a
      nerve injury and such multiple branches are suggested to be used to control, for
      example, prosthesis with many degrees of freedom. Transected rat sciatic nerve
      stumps were inserted into a nine mm long silicone tube, which contained four,
      five mm long, smaller tubes, thus leaving a five mm gap for regenerating nerve
      fibers. Six weeks later, several new nerve structures were formed not only in the
      four smaller tubes, but also in the spaces in-between. The 7-9 new continuous
      nerve structures, which were isolated as individual free nerves after removal of
      the tubes, were delineated by a perineurium and contained both myelinated and
      unmyelinated nerve fibers as well as blood vessels. Stimulation of the proximal
      nerve elicited contractions in distal muscles. Thin metal electrodes, inserted
      initially into the smaller tubes in some experiments, became embedded in the new
      nerve structures and when stimulated contractions of the distal muscles were
      observed. The "tubes within a tube" technique, creating multiple new nerves from
      a single "mother" nerve, can be used to record multiple signals for prosthetic
      device control or as sources for supply of multiple denervated targets. 

PMID- 24864257
TI  - Treatment of malignant gliomas in elderly patients: a concise overview of the
      literature.
AB  - Gliomas are the most frequent primary brain tumors and the incidence data has
      increased in the elderly population. Unfortunately, prospective studies on this
      population are few and so the right treatment is unknown. In the elderly patients
      no standard treatment has been established and therefore the optimal treatment
      should be individualized. We performed a review analyzing the prognostic and
      predictive factors, the clinical studies, and the correct management of this
      population. 

PMID- 24864256
TI  - Serial serum leukocyte apoptosis levels as predictors of outcome in acute
      traumatic brain injury.
AB  - BACKGROUND: Apoptosis associates with secondary brain injury after traumatic
      brain injury (TBI). This study posits that serum leukocyte apoptosis levels in
      acute TBI are predictive of outcome. METHODS: Two hundred and twenty-nine blood
      samples from 88 patients after acute TBI were obtained on admission and on Days 4
      and 7. Serial apoptosis levels of different leukocyte subsets were examined in 88
      TBI patients and 27 control subjects. RESULTS: The leukocyte apoptosis was
      significantly higher in TBI patients than in controls. Brief unconsciousness (P =
      0.009), motor deficits (P <= 0.001), GCS (P <= 0.001), ISS (P = 0.001), WBC count
      (P = 0.015), late apoptosis in lymphocytes and monocytes on Day 1 (P = 0.004 and
      P = 0.022, resp.), subdural hemorrhage on initial brain CT (P = 0.002),
      neurosurgical intervention (P <= 0.001), and acute posttraumatic seizure (P =
      0.046) were significant risk factors of outcome. Only motor deficits (P = 0.033)
      and late apoptosis in monocytes on Day 1 (P = 0.037) were independently
      associated with outcome. A cutoff value of 5.72% of late apoptosis in monocytes
      was associated with poor outcome in acute TBI patients. CONCLUSION: There are
      varying degrees of apoptosis in patients following TBI and in healthy
      individuals. Such differential expression suggests that apoptosis in different
      leukocyte subsets plays an important role in outcome following injury.

PMID- 24864258
TI  - Combinatorial control of transgene expression by hypoxia-responsive promoter and
      microrna regulation for neural stem cell-based cancer therapy.
AB  - Owing to their strong migratory capacity, tumor tropism, and tumor inhibitory
      effect, neural stem cells (NSCs) have recently emerged as one of the most
      attractive gene delivery vectors for cancer therapy. However, further animal
      studies found that proportional NSC vectors were distributed to nontarget organs
      after intravenous injection and the nonspecific transgene expression led to
      significant cytotoxic effects in these organs. Hence, an expression cassette that
      controls the transgene expression within NSC vectors in a tumor site-specific
      manner is desired. Considering hypoxia as a hallmark of tumor microenvironment,
      we have developed a novel NSC vector platform coupling transcriptional targeting
      with microRNA (miRNA) regulation for tumor hypoxia targeting. This combinatorial
      vector employed a hypoxia-responsive promoter and repeated targeting sequences of
      an miRNA that is enriched in NSCs but downregulated upon hypoxia induction to
      control the transgene expression. This resulted in significantly improved hypoxic
      selectivity over the use of a control vector without miRNA regulation. Thus,
      incorporating miRNA regulation into a transcriptional targeting vector adds an
      extra layer of security to prevent off-target transgene expression and should be
      useful for the development of NSC vectors with high targeting specifcity for
      cancer therapy. 

PMID- 24864259
TI  - In search of the active metabolites of an anticancer piperazinedione, TW01003, in
      rats.
AB  - TW01003, a piperazinedione derivative designed as an antimitotic agent, exhibited
      potent anticancer and antiangiogenesis activities in mice. However, oral
      administration of this compound in rats led to poor systemic bioavailability
      which suggested that in vivo efficacy might come from its metabolites. This
      report describes the identification of TW01003 metabolites in pig and Wistar
      rats. Following intravenous administration of TW01003, pig urine samples were
      subjected to sulfatase and glucuronidase treatment to monitor the
      biotransformation products. Rats were given TW01003 both intravenously and
      orally, and blood samples were collected and then analyzed by HPLC to
      quantitatively determine the metabolic transformation of TW01003 to its
      metabolite. A sulfate conjugate, TW01003 sulfate, was identified as the major
      metabolite for TW01003 after intravenous injection in both pig and rats. However,
      in rats, the glucuronide conjugate became major metabolite 30 min after TW01003
      oral dosing. Pharmacokinetic analysis after intravenous administration of TW01003
      indicated that TW01003 sulfate had a systemic bioavailability 2.5 times higher,
      volume of distribution three times higher, residence time seven times longer, and
      clearance rate 2.3 times lower compared to TW01003. Our results indicate that the
      potent anticancer and antiangiogenesis activities of TW01003 might not come from
      TW01003 per se but from its metabolites TW01003 sulfate. 

PMID- 24864260
TI  - Epithelial-mesenchymal transition regulated by EphA2 contributes to vasculogenic
      mimicry formation of head and neck squamous cell carcinoma.
AB  - PURPOSE: Vasculogenic mimicry (VM) was related to invasion and metastasis of head
      and neck squamous cell carcinoma (HNSCC) patients. This study was designed to
      investigate the role of EphA2 in VM formation of HNSCC. METHODS: The SiRNA
      technique was used to knock down the expression of EphA2 in vitro. The ability of
      cell migration and invasion were measured by transwell and wound healing assays;
      three-dimensional culture was used to detect the ability of channel-like
      structure formation; Western blot was used to detect the expression of epithelial
      mesenchymal transition- (EMT-) related molecules in vitro. Further
      semiquantitative real-time RT-PCR assays and immunohistochemistry were used to
      demonstrate expression of EphA2 and EMT-related molecules according to VM
      presence or not in human tissue. RESULTS: Knocking down EphA2 in vitro leads to
      disabled channel-like structure formation, reduction of invasion and migration
      ability, and reverse of EMT-related markers. Both semiquantitative real-time RT
      PCR and immunohistochemistry showed that expressions of EphA2, Twist, and
      Vimentin were higher in the VM-positive group than in the VM-negative group
      significantly, while expressions of E-cadherin, claudin4, and DSG-3 were reverse.
      CONCLUSIONS: EphA2 played a key role in VM formation of HNSCC through regulation
      of EMT.

PMID- 24864262
TI  - Phytochemical screening, physicochemical properties, acute toxicity testing and
      screening of hypoglycaemic activity of extracts of Eremurus himalaicus baker in
      normoglycaemic Wistar strain albino rats.
AB  - In the present study EtOAc, MeOH, and aqueous extracts of Eremurus himalaicus
      were evaluated for hypoglycaemic effect in normal rats using both oral glucose
      tolerance test and 14-day oral administration study. Phytochemical and
      physicochemical screening was also done. In oral glucose tolerance test the
      aqueous and MeOH extracts of Eremurus himalaicus at a dose level of 500 mg/kg
      body weight prior to glucose load resulted in a significant fall in blood glucose
      level within 150 min. of glucose administration. The aqueous extract at a dose
      level of 250 mg/kg body weight and 500 mg/kg body weight also showed good
      hypoglycaemic response (P < 0.001); this was followed by MeOH extract at a dose
      level of 500 mg/kg body weight (P < 0.05), while MeOH extract at dose level of
      250 mg/kg body weight and ethyl acetate extract at dose level of 250 mg/kg body
      weight and 500 mg/kg body weight exhibited insignificant effect. Phytochemical
      screening of extracts revealed the presence of alkaloids, terpenoids, phenolics,
      tannins, saponins, cardiac glycosides, and flavonoids. The results indicate that
      aqueous extract possess significant hypoglycaemic activity in normoglycaemic rats
      which may be attributed to the above-mentioned chemical constituents.

PMID- 24864261
TI  - Exogenous IL-4-expressing bone marrow mesenchymal stem cells for the treatment of
      autoimmune sensorineural hearing loss in a guinea pig model.
AB  - Bone marrow mesenchymal stem cells (BMSCs) expressing recombinant IL-4 have the
      potential to remediate inflammatory diseases. We thus investigated whether BMSCs
      expressing exogenous IL-4 could alleviate autoimmune sensorineural hearing loss.
      BMSCs isolated from guinea pigs were transfected with recombinant lentivirus
      expressing IL-4. A total of 33 animals were divided into three groups. Group A
      received scala tympani injection of IL-4-expressing BMSCs, and Group B received
      control vector-expressing BMSCs, and Group C received phosphate-buffered saline.
      The distribution of implanted BMSCs in the inner ears was assessed by
      immunohistochemistry and fluorescence microscopy. Auditory brain-stem response
      (ABR) was monitored to evaluate the auditory changes. Following BMSCs
      transplantation, the threshold levels of ABR wave III decreased in Groups A and B
      and significant differences were observed between these two groups (P < 0.05).
      Transplanted BMSCs distributed in the scala tympani and scala vestibuli. In some
      ears with hearing loss, there was a decrease in the number of spiral ganglion
      cells and varying degrees of endolymphatic hydrops or floccule. Following
      transplantation, the lentivirus-infected BMSCs migrated to the inner ear and
      produced IL-4. Our results demonstrate that, upon transplantation, BMSCs and
      BMSCs expressing recombinant IL-4 have the ability to remediate the inflammatory
      injury in autoimmune inner ear diseases.

PMID- 24864263
TI  - Agent-based modeling of the immune system: NetLogo, a promising framework.
AB  - Several components that interact with each other to evolve a complex, and, in
      some cases, unexpected behavior, represents one of the main and fascinating
      features of the mammalian immune system. Agent-based modeling and cellular
      automata belong to a class of discrete mathematical approaches in which entities
      (agents) sense local information and undertake actions over time according to
      predefined rules. The strength of this approach is characterized by the
      appearance of a global behavior that emerges from interactions among agents. This
      behavior is unpredictable, as it does not follow linear rules. There are a lot of
      works that investigates the immune system with agent-based modeling and cellular
      automata. They have shown the ability to see clearly and intuitively into the
      nature of immunological processes. NetLogo is a multiagent programming language
      and modeling environment for simulating complex phenomena. It is designed for
      both research and education and is used across a wide range of disciplines and
      education levels. In this paper, we summarize NetLogo applications to immunology
      and, particularly, how this framework can help in the development and formulation
      of hypotheses that might drive further experimental investigations of disease
      mechanisms. 

PMID- 24864264
TI  - Absence of cospeciation between the uncultured Frankia microsymbionts and the
      disjunct actinorhizal Coriaria species.
AB  - Coriaria is an actinorhizal plant that forms root nodules in symbiosis with
      nitrogen-fixing actinobacteria of the genus Frankia. This symbiotic association
      has drawn interest because of the disjunct geographical distribution of Coriaria
      in four separate areas of the world and in the context of evolutionary
      relationships between host plants and their uncultured microsymbionts. The
      evolution of Frankia-Coriaria symbioses was examined from a phylogenetic
      viewpoint using multiple genetic markers in both bacteria and host-plant
      partners. Total DNA extracted from root nodules collected from five species: C.
      myrtifolia, C. arborea, C. nepalensis, C. japonica, and C. microphylla, growing
      in the Mediterranean area (Morocco and France), New Zealand, Pakistan, Japan, and
      Mexico, respectively, was used to amplify glnA gene (glutamine synthetase), dnaA
      gene (chromosome replication initiator), and the nif DK IGS (intergenic spacer
      between nifD and nifK genes) in Frankia and the matK gene (chloroplast-encoded
      maturase K) and the intergenic transcribed spacers (18S rRNA-ITS1-5.8S rRNA-ITS2
      28S rRNA) in Coriaria species. Phylogenetic reconstruction indicated that the
      radiations of Frankia strains and Coriaria species are not congruent. The lack of
      cospeciation between the two symbiotic partners may be explained by host shift at
      high taxonomic rank together with wind dispersal and/or survival in nonhost
      rhizosphere. 

PMID- 24864265
TI  - FOXO transcription factors: their clinical significance and regulation.
AB  - Members of the class O of forkhead box transcription factors (FOXO) have
      important roles in metabolism, cellular proliferation, stress resistance, and
      apoptosis. The activity of FOXOs is tightly regulated by posttranslational
      modification, including phosphorylation, acetylation, and ubiquitylation.
      Activation of cell survival pathways such as phosphoinositide-3-kinase/AKT/IKK or
      RAS/mitogen-activated protein kinase phosphorylates FOXOs at different sites
      which regulate FOXOs nuclear localization or degradation. FOXO transcription
      factors are upregulated in a number of cell types including hepatocytes,
      fibroblasts, osteoblasts, keratinocytes, endothelial cells, pericytes, and
      cardiac myocytes. They are involved in a number of pathologic and physiologic
      processes that include proliferation, apoptosis, autophagy, metabolism,
      inflammation, cytokine expression, immunity, differentiation, and resistance to
      oxidative stress. These processes impact a number of clinical conditions such as
      carcinogenesis, diabetes, diabetic complications, cardiovascular disease, host
      response, and wound healing. In this paper, we focus on the potential role of
      FOXOs in different disease models and the regulation of FOXOs by various stimuli.

PMID- 24864267
TI  - Artificial extracellular matrices with oversulfated glycosaminoglycan derivatives
      promote the differentiation of osteoblast-precursor cells and premature
      osteoblasts.
AB  - Sulfated glycosaminoglycans (GAG) are components of the bone marrow stem cell
      niche and to a minor extent of mature bone tissue with important functions in
      regulating stem cell lineage commitment and differentiation. We anticipated that
      artificial extracellular matrices (aECM) composed of collagen I and synthetically
      oversulfated GAG derivatives affect preferentially the differentiation of
      osteoblast-precursor cells and early osteoblasts. A set of gradually sulfated
      chondroitin sulfate and hyaluronan derivatives was used for the preparation of
      aECM. All these matrices were analysed with human bone marrow stromal cells to
      identify the most potent aECM and to determine the influence of the degree and
      position of sulfate groups and the kind of disaccharide units on the osteogenic
      differentiation. Oversulfated GAG derivatives with a sulfate group at the C-6
      position of the N-acetylglycosamine revealed the most pronounced proosteogenic
      effect as determined by tissue nonspecific alkaline phosphatase activity and
      calcium deposition. A subset of the aECM was further analysed with different
      primary osteoblasts and cell lines reflecting different maturation stages to test
      whether the effect of sulfated GAG derivatives depends on the maturation status
      of the cells. It was shown that the proosteogenic effect of aECM was most
      prominent in early osteoblasts. 

PMID- 24864268
TI  - The pathology of T cells in systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is characterized by the production of a wide
      array of autoantibodies. Thus, the condition was traditionally classified as a "B
      cell disease". Compelling evidence has however shown that without the assistance
      of the helper T lymphocytes, it is indeed difficult for the "helpless" B cells to
      become functional enough to trigger SLE-related inflammation. T cells have been
      recognized to be crucial in the pathogenicity of SLE through their capabilities
      to communicate with and offer enormous help to B cells for driving autoantibody
      production. Recently, a number of phenotypic and functional alterations which
      increase the propensity to trigger lupus-related inflammation have been
      identified in lupus T cells. Here, potential mechanisms involving alterations in
      T-cell receptor expressions, postreceptor downstream signalling, epigenetics, and
      oxidative stress which favour activation of lupus T cells will be discussed.
      Additionally, how regulatory CD4+, CD8+, and gammadelta T cells tune down lupus
      related inflammation will be highlighted. Lastly, while currently available
      outcomes of clinical trials evaluating therapeutic agents which manipulate the T
      cells such as calcineurin inhibitors indicate that they are at least as
      efficacious and safe as conventional immunosuppressants in treating lupus
      glomerulonephritis, larger clinical trials are undoubtedly required to validate
      these as-yet favourable findings. 

PMID- 24864266
TI  - Genetics of type 2 diabetes: insights into the pathogenesis and its clinical
      application.
AB  - With rapidly increasing prevalence, diabetes has become one of the major causes
      of mortality worldwide. According to the latest studies, genetic information
      makes substantial contributions towards the prediction of diabetes risk and
      individualized antidiabetic treatment. To date, approximately 70 susceptibility
      genes have been identified as being associated with type 2 diabetes (T2D) at a
      genome-wide significant level (P < 5 * 10(-8)). However, all the genetic loci
      identified so far account for only about 10% of the overall heritability of T2D.
      In addition, how these novel susceptibility loci correlate with the
      pathophysiology of the disease remains largely unknown. This review covers the
      major genetic studies on the risk of T2D based on ethnicity and briefly discusses
      the potential mechanisms and clinical utility of the genetic information
      underlying T2D. 

PMID- 24864271
TI  - Facial fibrofolliculomas as indicator for renal cell cancer.

PMID- 24864272
TI  - Five-year relative survival rate of breast cancer in the USA, Europe and Japan.

PMID- 24864269
TI  - Improving cytomegalovirus-specific T cell reconstitution after haploidentical
      stem cell transplantation.
AB  - Cytomegalovirus (CMV) infection and delayed immune reconstitution (IR) remain
      serious obstacles for successful haploidentical stem cell transplantation (haplo
      SCT). CMV-specific IR varied according to whether patients received
      manipulated/unmanipulated grafts or myeloablative/reduced intensity conditioning.
      CMV infection commonly occurs following impaired IR of T cell and its subsets.
      Here, we discuss the factors that influence IR based on currently available
      evidence. Adoptive transfer of donor T cells to improve CMV-specific IR is
      discussed. One should choose grafts from CMV-positive donors for transplant into
      CMV-positive recipients (D+/R+) because this will result in better IR than would
      grafts from CMV-negative donors (D-/R+). Stem cell source and donor age are other
      important factors. Posttransplant complications, including graft-versus-host
      disease and CMV infection, as well as their associated treatments, should also be
      considered. The effects of varying degrees of HLA disparity and conditioning
      regimens are more controversial. As many of these factors and strategies are
      considered in the setting of haplo-SCT, it is anticipated that haplo-SCT will
      continue to advance, further expanding our understanding of IR and CMV infection.

PMID- 24864270
TI  - Chinese SLE treatment and research group registry: III. association of
      autoantibodies with clinical manifestations in Chinese patients with systemic
      lupus erythematosus.
AB  - We investigated the characteristics of Chinese SLE patients by analyzing the
      association between specific autoantibodies and clinical manifestations of 2104
      SLE patients from registry data of CSTAR cohort. Significant (P<0.05)
      associations were found between anti-Sm antibody, anti-rRNP antibody, and malar
      rash; between anti-RNP antibody, anti-SSA antibody, and pulmonary arterial
      hypertension (PAH); between anti-SSB antibody and hematologic involvement; and
      between anti-dsDNA antibody and nephropathy. APL antibody was associated with
      hematologic involvement, interstitial lung disease, and a lower prevalence of
      oral ulcerations (P<0.05). Associations were also found between anti-dsDNA
      antibody and a lower prevalence of photosensitivity, and between anti-SSA
      antibody and a lower prevalence of nephropathy (P<0.05). Most of these findings
      were consistent with other studies in the literature but this study is the first
      report on the association between anti-SSA and a lower prevalence of nephropathy.
      The correlations of specific autoantibodies and clinical manifestations could
      provide clues for physicians to predict organ damages in SLE patients. We suggest
      that a thorough screening of autoantibodies should be carried out when the
      diagnosis of SLE is established, and repeated echocardiography annually in SLE
      patients with anti-RNP or anti-SSA antibody should be performed.

PMID- 24864273
TI  - Diabetic nephropathy induces alterations in the glomerular and tubule lipid
      profiles.
AB  - Diabetic nephropathy (DN) is a major life-threatening complication of diabetes.
      Renal lesions affect glomeruli and tubules, but the pathogenesis is not
      completely understood. Phospholipids and glycolipids are molecules that carry out
      multiple cell functions in health and disease, and their role in DN pathogenesis
      is unknown. We employed high spatial resolution MALDI imaging MS to determine
      lipid changes in kidneys of eNOS(-/-) db/db mice, a robust model of DN.
      Phospholipid and glycolipid structures, localization patterns, and relative
      tissue levels were determined in individual renal glomeruli and tubules without
      disturbing tissue morphology. A significant increase in the levels of specific
      glomerular and tubular lipid species from four different classes, i.e.,
      gangliosides, sulfoglycosphingolipids, lysophospholipids, and
      phosphatidylethanolamines, was detected in diabetic kidneys compared with
      nondiabetic controls. Inhibition of nonenzymatic oxidative and glycoxidative
      pathways attenuated the increase in lipid levels and ameliorated renal pathology,
      even though blood glucose levels remained unchanged. Our data demonstrate that
      the levels of specific phospho- and glycolipids in glomeruli and/or tubules are
      associated with diabetic renal pathology. We suggest that hyperglycemia-induced
      DN pathogenic mechanisms require intermediate oxidative steps that involve
      specific phospholipid and glycolipid species.

PMID- 24864275
TI  - Systematic review and meta-analysis of behavioral interventions to improve child
      pedestrian safety.
AB  - OBJECTIVE: Pedestrian injuries represent a pediatric public health challenge.
      This systematic review/meta-analysis evaluated behavioral interventions to teach
      children pedestrian safety. METHODS: Multiple strategies derived eligible
      manuscripts (published before April 1, 2013, randomized design, evaluated
      behavioral child pedestrian safety interventions). Screening 1,951 abstracts
      yielded 125 full-text retrievals. 25 were retained for data extraction, and 6
      were later omitted due to insufficient data. In all, 19 articles reporting 25
      studies were included. Risk of bias and quality of evidence were assessed.
      RESULTS: Behavioral interventions generally improve children's pedestrian safety,
      both immediately after training and at follow-up several months later. Quality of
      the evidence was low to moderate. Available evidence suggested interventions
      targeting dash-out prevention, crossing at parked cars, and selecting safe routes
      across intersections were effective. Individualized/small-group training for
      children was the most effective training strategy based on available evidence.
      CONCLUSIONS: Behaviorally based interventions improve children's pedestrian
      safety. Efforts should continue to develop creative, cost-efficient, and
      effective interventions.

PMID- 24864274
TI  - PPARdelta activation attenuates hepatic steatosis in Ldlr-/- mice by enhanced fat
      oxidation, reduced lipogenesis, and improved insulin sensitivity.
AB  - PPARdelta regulates systemic lipid homeostasis and inflammation, but its role in
      hepatic lipid metabolism remains unclear. Here, we examine whether intervening
      with a selective PPARdelta agonist corrects hepatic steatosis induced by a high
      fat, cholesterol-containing (HFHC) diet. Ldlr(-/-) mice were fed a chow or HFHC
      diet (42% fat, 0.2% cholesterol) for 4 weeks. For an additional 8 weeks, the HFHC
      group was fed HFHC or HFHC plus GW1516 (3 mg/kg/day). GW1516-intervention
      significantly attenuated liver TG accumulation by induction of FA beta-oxidation
      and attenuation of FA synthesis. In primary mouse hepatocytes, GW1516 treatment
      stimulated AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC)
      phosphorylation in WT hepatocytes, but not AMPKbeta1(-/-) hepatocytes. However,
      FA oxidation was only partially reduced in AMPKbeta1(-/-) hepatocytes, suggesting
      an AMPK-independent contribution to the GW1516 effect. Similarly, PPARdelta
      mediated attenuation of FA synthesis was partially due to AMPK activation, as
      GW1516 reduced lipogenesis in WT hepatocytes but not AMPKbeta1(-/-) hepatocytes.
      HFHC-fed animals were hyperinsulinemic and exhibited selective hepatic insulin
      resistance, which contributed to elevated fasting FA synthesis and hyperglycemia.
      GW1516 intervention normalized fasting hyperinsulinemia and selective hepatic
      insulin resistance and attenuated fasting FA synthesis and hyperglycemia. The
      HFHC diet polarized the liver toward a proinflammatory M1 state, which was
      reversed by GW1516 intervention. Thus, PPARdelta agonist treatment inhibits the
      progression of preestablished hepatic steatosis.

PMID- 24864276
TI  - Systematic review and meta-analysis of cognitive interventions for children with
      central nervous system disorders and neurodevelopmental disorders.
AB  - OBJECTIVE: To assess the efficacy of cognitive interventions for children with
      neurological disorders, acquired brain injuries, and neurodevelopmental
      disorders. METHOD: We searched for randomized controlled trials of cognitive
      interventions; 13 studies met inclusion criteria. Risk of bias was rated for each
      study. Standardized effect size estimates were examined in 7 outcome domains. The
      overall quality of evidence was rated using the Grading of Recommendations
      Assessment, Development and Evaluation system. RESULTS: Significant positive
      treatment effects were found in all outcome domains aside from inhibitory
      control. Effects were large for attention, working memory, and memory tasks, and
      small for academic achievement and behavior rating scales. Results exhibited
      substantial heterogeneity in all domains. Overall quality of evidence was rated
      very low in all domains, suggesting substantial uncertainty about effect size
      estimates. DISCUSSION: The results provide some evidence of a positive benefit
      from cognitive interventions, but cannot be regarded as robust given the overall
      very low quality of the evidence.

PMID- 24864277
TI  - Observed macro- and micro-level parenting behaviors during preadolescent family
      interactions as predictors of adjustment in emerging adults with and without
      spina bifida.
AB  - OBJECTIVE: To examine observed autonomy-promoting and -inhibiting parenting
      behaviors during preadolescence as predictors of adjustment outcomes in emerging
      adults with and without spina bifida (SB). METHODS: Demographic and videotaped
      interaction data were collected from families with 8/9-year-old children with SB
      (n = 68) and a matched group of typically developing youth (n = 68). Observed
      interaction data were coded with macro- and micro-coding schemes. Measures of
      emerging adulthood adjustment were collected 10 years later (ages 18/19 years; n
      = 50 and n = 60 for SB and comparison groups, respectively). RESULTS: Autonomy
      promoting (behavioral control, autonomy-relatedness) and -inhibiting
      (psychological control) observed preadolescent parenting behaviors prospectively
      predicted emerging adulthood adjustment, particularly within educational, social,
      and emotional domains. Interestingly, high parent undermining of relatedness
      predicted better educational and social adjustment in the SB sample CONCLUSIONS:
      Parenting behaviors related to autonomy have long-term consequences for
      adjustment in emerging adults with and without SB.

PMID- 24864279
TI  - Effects of a dietary antioxidant blend and vitamin E on fatty acid profile, liver
      function, and inflammatory response in broiler chickens fed a diet high in
      oxidants.
AB  - The aim of the current study was to determine the effects of a dietary
      antioxidant blend and vitamin E on fatty acid profile, inflammatory response, and
      liver function. Cobb 500 male broilers (n = 1,200, d 0) were randomly distributed
      into 6 treatments with 10 replicate floor pens. Treatments included (1) a high
      oxidant diet, with vitamin E at 10 IU/kg, 3% oxidized oil, 3% polyunsaturated
      fatty acids (PUFA) source (HO); (2) the HO diet with vitamin E at 200 IU/kg (VE);
      (3) the HO diet with an antioxidant blend at 135 mg/kg (AOX); (4) the HO diet
      with both vitamin E at 200 IU/kg and an antioxidant blend at 135 mg/kg (VE+AOX);
      (5) standard control (SC); and (6) a positive control, which was the SC diet with
      an antioxidant blend at 135 mg/kg. The concentrations of 20:4, 20:5, 22:5, 22:6,
      and all the n-3 fatty acids were greater in the abdominal fat of HO, VE, AOX, and
      VE+AOX birds than SC and positive control birds on d 21 and 42 (P < 0.001).
      Compared with HO treatment, AOX and VE+AOX preserved the deposition of PUFA
      better (P < 0.001). The HO birds had greater concentrations of aspartate
      aminotransferase on d 21 and 42, and gamma-glutamyl transferase on d 21, whereas
      AOX and VE+AOX chickens had restored gamma-glutamyl transferase concentration (P
      < 0.01). The inflammation scores of abdominal fat of AOX and VE+AOX birds were
      lower than the HO on d 21 (P < 0.001). Compared with SC, the VE and VE+AOX birds
      exhibited greater vacuole scores on d 21 and 42 (P < 0.01). The lower vacuoles
      score in SC was associated with a greater expression of peroxisome proliferator
      activated receptor -gamma and -alpha (P < 0.05). The expression of inflammatory
      genes in the liver did not differ among treatments. In conclusion, the AOX and
      AOX+VE diets were effective in preserving PUFA in the abdominal fat, moderately
      improved liver function, and reduced inflammation in fat. 

PMID- 24864280
TI  - Measurement of water-holding capacity in raw and freeze-dried broiler breast meat
      with visible and near-infrared spectroscopy.
AB  - The feasibility of using visible/near-infrared spectroscopy (vis/NIR) to
      segregate broiler breast fillets by water-holding capacity (WHC) was determined.
      Broiler breast fillets (n = 72) were selected from a commercial deboning line
      based on visual color assessment. Meat color (L*a*b*), pH (2 and 24 h), drip
      loss, and salt-induced water uptake were measured. Reflectance measurements were
      recorded from 400 to 2,500 nm in both raw and freeze-dried breast meat samples.
      Raw and freeze-dried samples had similar spectra in the visible region (400-750
      nm), but the freeze-dried samples exhibited numerous bands in the NIR region (750
      2,500 nm) corresponding to muscle proteins and lipids that were not observed in
      the NIR spectra of the raw samples. Linear discriminate analyses were used to
      classify fillets as high-WHC or low-WHC according to predicted meat quality
      characteristics. Using the visible spectra (400-750 nm), fillets could be
      correctly classified into high-WHC and low-WHC groups based on drip loss and salt
      induced water uptake with 88 to 92% accuracy in raw samples and 79 to 86%
      accuracy in freeze-dried samples. Using the NIR spectra (750-2,500 nm), fillets
      could be correctly classified into high-WHC and low-WHC groups with 74 to 76%
      accuracy in raw samples and 85 to 86% accuracy in freeze-dried samples. Thus,
      freeze-drying enhanced the accuracy of WHC classification using the NIR portion
      of the spectra. Data from this study demonstrate the potential for utilizing
      vis/NIR spectroscopy as a method for classifying broiler breast meat according to
      WHC. 

PMID- 24864278
TI  - High-dose concurrent chemo-proton therapy for Stage III NSCLC: preliminary
      results of a Phase II study.
AB  - The aim of this report is to present the preliminary results of a Phase II study
      of high-dose (74 Gy RBE) proton beam therapy (PBT) with concurrent chemotherapy
      for unresectable locally advanced non-small-cell lung cancer (NSCLC). Patients
      were treated with PBT and chemotherapy with monthly cisplatin (on Day 1) and
      vinorelbine (on Days 1 and 8). The treatment doses were 74 Gy RBE for the primary
      site and 66 Gy RBE for the lymph nodes without elective lymph nodes. Adapted
      planning was made during the treatment. A total of 15 patients with Stage III
      NSCLC (IIIA: 4, IIIB: 11) were evaluated in this study. The median follow-up
      period was 21.7 months. None of the patients experienced Grade 4 or 5 non
      hematologic toxicities. Acute pneumonitis was observed in three patients (Grade 1
      in one, and Grade 3 in two), but Grade 3 pneumonitis was considered to be non
      proton-related. Grade 3 acute esophagitis and dermatitis were observed in one and
      two patients, respectively. Severe ( >= Grade 3) leukocytopenia, neutropenia and
      thrombocytopenia were observed in 10 patients, seven patients and one patient,
      respectively. Late radiation Grades 2 and 3 pneumonitis was observed in one
      patient each. Six patients (40%) experienced local recurrence at the primary site
      and were treated with 74 Gy RBE. Disease progression was observed in 11 patients.
      The mean survival time was 26.7 months. We concluded that high-dose PBT with
      concurrent chemotherapy is safe to use in the treatment of unresectable Stage III
      NSCLC. 

PMID- 24864281
TI  - Effects of stocking density on growth performance, carcass traits, and foot pad
      lesions of White Pekin ducks.
AB  - Two experiments were conducted to study the effects of stocking density on growth
      performance, carcass yield, and foot pad lesions of White Pekin ducks from hatch
      to 14 d of age (experiment 1) and from 14 to 42 d of age (experiment 2),
      respectively. All ducks were reared in raised plastic wire-floor pens with a pen
      size of 30 m(2), and males and females were mixed at a ratio of 1:1 in each pen
      of both experiments. In experiment 1, a total of 10,200 ducks that were 1 d old
      were allotted to 20 pens according to the stocking densities of 13, 15, 17, 19,
      and 21 birds/m(2) (or 8.4, 9.7, 10.9, 11.9, and 13.0 kg of actually achieved
      BW/m(2)), respectively, with 4 replicates per treatment. In experiment 2, a total
      of 3,150 ducks that were 14 d old were allotted to 15 pens according to the
      stocking densities of 5, 6, 7, 8, and 9 birds/m(2) (or 17.0, 20.3, 23.6, 26.9,
      and 29.9 kg of actually achieved BW/m(2)), respectively, with 3 replicates per
      treatment. The stocking density had significant effects on final BW and weight
      gain of starter and growing ducks (P < 0.05), but not on feed/gain and mortality
      in both periods (P > 0.05). The final BW and weight gain of starter and growing
      ducks all decreased with increasing density (P < 0.05). Final BW and weight gain
      of starter ducks were reduced significantly as stocking density increased from 17
      to 21 birds/m(2) (P < 0.05). In addition, final BW and weight gain of growing
      ducks decreased significantly when stocking density was 9 birds/m(2) (P < 0.05).
      On the other hand, increasing stocking density did not markedly influence the
      carcass, breast meat, leg meat, abdominal fat, and foot pad lesions of growing
      ducks (P > 0.05). 

PMID- 24864282
TI  - Impact of thermal and organic acid treatment of feed on apparent ileal mineral
      absorption, tibial and liver mineral concentration, and tibia quality in
      broilers.
AB  - Minerals play an important role for growth and bone stability in broilers.
      Thermal treatment and inclusion of organic acids in feed may affect the mineral
      absorption and tibial quality in broilers. The study was conducted to investigate
      the effect of thermal processing of feed including pelleting (P), long-term
      conditioning at 85 degrees C (L), and expanding at 130 degrees C (E) without and
      with 1.5% of an acid mixture containing 64% formic and 25% propionic acid on the
      apparent ileal absorption (AIA) of calcium, phosphorus, magnesium, potassium,
      sodium, iron, copper, manganese, and zinc, their concentrations in liver and
      tibia, as well as various tibial quality parameters in broilers. In total, 480
      one-day-old Cobb broiler chicks were assigned using a completely randomized
      design with a 3 * 2 factorial arrangement. The ileal digesta, liver, and tibia
      were collected at d 35. The AIA of calcium and sodium was improved in group E
      compared with L (P <= 0.02 and P <= 0.01). Group P and E showed higher AIA for
      potassium than L (P <= 0.01). Bone ash content was increased in group E compared
      with L (P <= 0.04). The BW to bone weight ratio was lower and tibial zinc content
      was higher in group P compared with E (P <= 0.05). Tibial iron content was higher
      in group L than E (P <= 0.03). Acid addition did not affect AIA, mineral content
      in tibia, or tibial quality parameters. Thermal and acid treatment did not affect
      mineral concentrations in the liver, except an inconsistent interaction effect
      for DM content and sodium (P <= 0.03 and P <= 0.04, respectively). In conclusion,
      long-term thermal treatment reduced AIA of some minerals compared with short-term
      thermal treatments, but had no impact on tibia composition. Acid inclusion had no
      effect on AIA of minerals and tibia quality. Thermal treatment and the use of
      organic acids can therefore be considered as safe with regard to their impact on
      bone development in broilers. 

PMID- 24864284
TI  - The effect of protease, amylase, and nonstarch polysaccharide-degrading enzyme
      supplementation on nutrient utilization and growth performance of broiler
      chickens fed corn-soybean meal-based diets.
AB  - A study was conducted to determine if amylase and protease addition would improve
      nutrient digestion during the first 2 wk of growth. The experimental treatments
      included a control corn-soybean meal-based diet and diets supplemented with
      either amylase or amylase plus protease. No effect of enzyme supplementation was
      observed on BW gain and feed conversion ratio. This was corroborated by similar
      ileal starch and protein digestibility values, which averaged 96.8, 96.8, and
      96.9% and 83.9, 80.1, and 79.6%, respectively, for the control and for the
      amylase or amylase plus protease supplemented diets. Total tract digestibility of
      starch averaged 97.8, 97.7 and 97.7% for the 3 diets and was followed by a
      similar diet with AMEn values of 3,129, 3,129, and 3,106 kcal/kg. In another
      study, a 2(3) factorial arrangement of 8 dietary treatments was used to evaluate
      the effect of corn particle size (conventional or coarse vs. fine) and the
      addition of a nonstarch polysaccharide enzyme, amylase, or both on growth
      performance and nutrient utilization of broiler chickens from 1 to 21 d of age.
      Chickens fed a diet containing a conventionally ground corn (geometric mean
      diameter of 736 um) showed higher (P < 0.001) BW gain (808 vs. 750 g/bird) and
      lower feed conversion ratio (1.27 vs. 1.32) than those consuming a fine corn
      containing diet (geometric mean diameter of 482 um). This was further
      substantiated by a lower AMEn content (2,852 vs. 2,972 kcal/kg). Addition of
      amylase had no effect on growth performance of chickens fed a conventional corn
      containing diet, but improved BW gain, feed conversion ratio, and diet AMEn in
      those fed the finely ground corn, possibly due to increased starch digestion in
      the upper gut. Addition of nonstarch polysaccharide enzymes was effective for
      both diets, with the most pronounced effects observed in feed conversion ratio
      for the conventional corn-containing diet (1.27 vs. 1.23) and BW gain (750 vs.
      789 g/bird) for the fine corn-containing diet. This was followed by the same
      magnitude of difference in diet AMEn content, which increased from 2,972 to 3,042
      and 2,852 to 3,009 kcal/kg following enzyme addition.

PMID- 24864283
TI  - The effect of dietary alterations during rearing on feather condition in broiler
      breeder females.
AB  - In commercial production, broiler breeders are severely feed restricted to
      maintain healthy BW. This restriction can induce stereotypic behavior, including
      feather pecking, which has negative welfare implications for both the victim and
      performer. It has been suggested that the problem may be symptomatic of chronic
      hunger or the frustration of feeding motivation. In this study, we determined
      whether feather condition, as an indirect measure of feather pecking, could be
      improved via dietary manipulation. Six dietary treatments were tested, each with
      5 replicate pens of 9 to 12 birds. Control diets (C) were fed on a daily or skip
      a-day (SAD) basis. Alternative diets included soybean hulls as a bulking
      ingredient and calcium propionate (CaP) as an appetite suppressant of either a
      feed grade (F) or purified (P) quality. Both alternative diets were fed on either
      a daily or SAD basis. Five or 6 birds were randomly chosen from each pen and
      feather scored at 10, 14, 20, 26, and 36 wk of age. Six body parts (neck, back,
      wings, legs, vent area, tail) were given a score from 0 to 5 (0 = no feather
      damage, and 5 >= 50% feather loss with tissue damage). Scores were summed for
      each bird and averaged for each pen. Data were analyzed with room and feeding
      frequency as main factors and diet as the subfactor with repeated measures. There
      was an interaction between diet and time (P < 0.01) with the feather condition of
      the C birds worsening more quickly in comparison with the F and P birds. There
      was an interaction between feeding frequency and time (P = 0.015), with SAD-fed
      birds scoring better than daily-fed birds at 20, 26, and 36 wk. This interaction
      could indicate that SAD feeding increased satiety after the birds became
      accustomed to the schedule. Because feather condition was better with the
      alternative diets, this may indicate a reduction in stereotyped feather pecking
      with these diets. This suggests that the alternative diets increase satiety
      compared with the control diets. 

PMID- 24864285
TI  - Effects of monochromatic light stimuli on the development and Muc2 expression of
      goblet cells in broiler small intestines during embryogenesis.
AB  - The effects of monochromatic light on the ontogeny, differentiation, and Muc2
      expression level in goblet cells were studied in the small intestines of late
      stage broiler embryos. The embryos were exposed to blue light (B group), green
      light (G group), red light (R group), or darkness (D group) throughout the
      incubation period. On d 15 of incubation (E15), a few acidic goblet cells (only
      the sulfated subtype) were observed, and Muc2 mRNA expression was detected. On
      E18, however, neutral, acidic, and intermediate types, as well as the sulfated
      subtype, were observed in the small intestine, and a decreasing gradient of
      goblet cell density was found along the duodenum to ileum axis. Up to E21, 3
      types of goblet cells and 3 acidic cell subtypes were found in all the small
      intestines. The goblet cell density increased along the duodenum to ileum axis.
      Monochromatic light stimulation resulted in no significant differences in the
      density and types of goblet cells between the different treatment groups on E15
      and E18, but an increased Muc2 mRNA expression level was detected on E18 in the G
      group compared with the other treatment groups. On E21, the goblet cell density,
      proportion of acidic goblet cells, and Muc2 mRNA expression level increased in
      the G group compared with other treatment groups. These results suggest that the
      ontogeny and differentiation of goblet cells in broiler embryos display temporal
      and spatial differences. Green monochromatic light may have the potential to
      promote the proliferation and maturation of as well as the expression of Muc2
      mRNA in goblet cells of broiler embryos. 

PMID- 24864286
TI  - Low-fiber alfalfa (Medicago sativa L.) meal in the laying hen diet: effects on
      productive traits and egg quality.
AB  - This study was designed to determine the effects on laying performance and egg
      quality resulting from partial substitution of soybean meal (SBM) with low-fiber
      alfalfa (LFA; Medicago sativa L.) meal in the diet of early-phase laying hens.
      ISA Brown layers, 18 wk of age, were randomly allocated to 2 dietary treatments
      and fed for 10 wk. The hens were fed 2 wheat middling-based diets: a control
      diet, which contained SBM (15% of diet), and a test diet containing LFA (15% of
      diet) as the main protein source. Low-fiber alfalfa meal was obtained by a
      combination of sieving and air-classification processes. Feed intake was recorded
      daily, and egg production was calculated on a hen-day basis; eggs from each group
      were weekly collected to evaluate egg components and quality. The partial
      substitution of SBM with LFA had no adverse effect on growth performance of early
      phase laying hens. Egg production and none of the egg-quality traits examined
      were influenced by dietary treatment, except for yolk color (P < 0.001) and yolk
      percentage (P < 0.05) as well as yolk cholesterol and beta-carotene contents (P <
      0.001), which were improved in hens fed the LFA diet. Including LFA increased
      serum beta-carotene and reduced serum cholesterol concentrations (P < 0.001). Our
      results suggest that partially replacing conventional SBM as protein source with
      low-fiber alfalfa meal in the laying-hen diet can positively influence yolk
      quality without adversely affecting productive traits. 

PMID- 24864287
TI  - Short-term nutritional strategies before slaughter are effective in modulating
      the final pH and color of broiler breast meat.
AB  - The poultry meat industry is faced with various quality issues related to
      variations in the ultimate pH of breast meat. The aim of this study was to
      evaluate the possibility to control breast ultimate pH by distributing finishing
      diets varying in amino acid (AA) and energy content for a short period before
      slaughter. Experimental diets were distributed to PM3 broilers on the last 3 d
      before slaughter (36 d of age). They consisted of a control (C) diet (3,150
      kcal/kg; 200 g/kg of CP; 10.0 g/kg of true digestible Lys) with adequate amounts
      of AA other than Lys, 6 diets isocaloric to the control diet including 3 Lys
      deficient (8.0 g/kg) diets with an adequate (Lys-/AA), low (Lys-/AA-), or high
      (Lys-/AA+) amount of other essential AA calculated in relation to Lys, and 3 Lys
      rich (12.0 g/kg) diets with an adequate (Lys+/AA), low (Lys+/AA-), or high
      (Lys+/AA+) amount of other essential AA calculated in relation to Lys, and 2
      diets isoproteic to C with a high (3,300 kcal/kg, E+) or low (3,000 kcal/kg, E-)
      energy content. Broiler feed consumption and growth performance were slightly
      affected by AA and energy content during the finishing period. Feed intake (33-36
      d) was lower with the Lys+/AA+ and E+, and FCR between 24 and 36 d was higher
      with the Lys-/AA- and E- than with the C diet. Body weight at d 36 was lower in
      Lys-/AA-, Lys+/AA+, and E+ than in C, whereas the breast meat yield and abdominal
      fatness were not affected by diet. Lower pH values were observed in broilers fed
      Lys-deficient diets containing a high amount of other AA (Lys-/AA+) than in
      broilers fed diets containing low (AA-) or adequate (AA) amounts of other AA.
      This study shows that it is possible to alter the pH of breast meat by changing
      AA profile over a short period before slaughter, with limited impact on broiler
      growth and carcass composition. 

PMID- 24864288
TI  - Effect of dietary nonphytate phosphorus and calcium concentration on calcium
      appetite of broiler chicks.
AB  - The effect of dietary nonphytate P (nPP) and Ca concentration on the Ca appetite
      in broilers was evaluated. A total of 288 one-day-old male Ross 308 broilers were
      fed a commercial diet for 7 d then randomly allocated to 1 of 8 dietary
      treatments for a 28-d study. Diets were corn-soybean meal based and formulated to
      be nutritionally adequate except for nPP and Ca. Two concentrations of Ca (5.0
      and 10.0 g/kg) and 4 of nPP (2.5, 3.5, 4.5, and 5.5 g/kg) were used, and all
      birds had access to a separate Ca source (CaCO3). Bird performance, nutrient
      digestibility, and tibia ash were determined. Birds fed 5.0 g of Ca/kg diets
      consumed more (P < 0.01) of the separate Ca source than birds fed diets
      containing 10.0 g of Ca/kg. Increased consumption (P < 0.01) of the separate Ca
      source was associated with increasing nPP concentration. Bird performance was not
      influenced by dietary treatment. Birds fed 5.5 g of nPP/kg diets had lower (P <
      0.01) digestibility of DM, CP, and energy than the other groups. Phosphorus
      digestibility was reduced in birds fed high Ca diets and those fed 2.5 g of
      nPP/kg diets (P < 0.001). Birds fed 2.5 g of nPP/kg had lower tibia ash values
      than those fed higher concentrations of nPP while feeding diets containing 10.0 g
      of Ca/kg led to higher concentrations (P < 0.05) of tibia ash than for birds fed
      5.0 g of Ca/kg. This study confirms previous findings that birds are able to meet
      their Ca requirement when fed Ca separately from the mixed ration. Consumption of
      the separate Ca source responded to not only Ca concentration but also to the
      amount of nPP in the diet. These data suggest that dietary nPP concentration
      influences the Ca specific appetite of broilers, and this may indicate that birds
      attempt to regulate their intake of Ca relative to nPP. This may be mediated via
      a physiological mechanism to maintain an appropriate Ca:nPP intake. 

PMID- 24864289
TI  - Action of Brazilian propolis on hematological and serum biochemical parameters of
      Blue-fronted Amazons (Amazona aestiva, Linnaeus, 1758) in captivity.
AB  - The present study aimed to evaluate the effect of propolis use on hematological
      and serum biochemical parameters in Blue-fronted Amazons (Amazona aestiva). For
      this, 12 adult birds were distributed randomly into individual cages, divided
      into treatments with different propolis levels (A = 0.0%; B = 0.5%; and C =
      1.0%), in 3 distinct phases (I, II, and III), with 15-d duration for phases I and
      III and 30 d for phase II, totaling 60 d. In phases I and III, all birds received
      treatment A ration, and in phase II received A, B, or C (4 birds per treatment).
      At the end of each phase, blood was collected for biochemical and hematological
      evaluations. The variables were analyzed by ANOVA (P < 0.05). Results suggest
      that 0.5% propolis reduced lactate dehydrogenase levels, whereas treatment B
      augmented hemoglobin concentrations and eosinophil count. It is concluded that
      0.5% propolis improves levels of lactate dehydrogenase, hemoglobin, and
      eosinophils. 

PMID- 24864290
TI  - Shelf-life extension of vacuum-packaged meat from pheasant (Phasianus colchicus)
      by lactic acid treatment.
AB  - We investigated the influence of lactic acid treatment of pheasant meat before
      vacuum-packaged storage of 3, 7, and 10 d at +6 degrees C on microbiota and pH.
      Breast muscle samples were collected from carcasses of slaughtered as well as
      from hunted (shot) wild pheasants. Immersion of meat samples in 3% (wt/wt) lactic
      acid for 60 s effectuated a significant drop in pH of approximately 0.5 to 0.7
      units, which remained during the entire storage period. In parallel, total
      aerobic counts of such treated and stored samples were on an average 1.5 to 1.7
      log units lower than in non-acid-treated samples. Similar results were found for
      Enterobacteriaceae. A significant decrease in pH was measured at d 7 and 10 in
      the acid-treated samples in comparison with the untreated ones. In summary, the
      immersion of pheasant breast meat cuts in dilute lactic acid significantly
      reduced microbiota during vacuum-packed storage, even at slight temperature abuse
      conditions. 

PMID- 24864291
TI  - Forsythia suspensa extract attenuates corticosterone-induced growth inhibition,
      oxidative injury, and immune depression in broilers.
AB  - Forsythia suspensa extract (FSE) has been demonstrated to attenuate physiological
      stress induced by high temperature or high stocking density. This experiment was
      conducted with 144 male Arbor Acre broilers (1-d-old, weighing 42.7 +/- 1.7 g) to
      determine the effects of FSE on performance, nutrient digestibility, antioxidant
      activities, serum metabolites, and immune parameters for birds treated with
      corticosterone (CS). The birds were randomly allotted to 1 of 4 treatments in a 2
      * 2 factorial arrangement that included FSE supplementation (0 or 100 mg/kg) and
      CS administration (0 or 20 mg/kg of diet for 7 consecutive days starting on d
      14). The feeding program consisted of a starter diet from d 1 to 21 and a
      finisher diet from d 22 to 42. Corticosterone administration decreased (P < 0.01)
      ADG and impaired (P < 0.01) feed conversion ratio in both phases and overall,
      which were alleviated (P < 0.01) by dietary FSE supplementation in the finisher
      phase and overall. At d 21, CS administration caused decreases (P < 0.05) in the
      apparent digestibility of energy, relative weight of bursa and thymus, total
      antioxidant capacity, superoxide dismutase (SOD) activity, and antibody titers to
      Newcastle disease virus (NDV); however, serum malondialdehyde and uric acid were
      increased. All of these changes were attenuated (P < 0.05) by dietary FSE
      supplementation. At d 42, FSE supplementation improved (P < 0.05) the apparent
      digestibility of DM and CP, relative weights of bursa, SOD activity, and antibody
      titers to NDV, which were impaired by CS administration. Interactions (P < 0.05)
      were noted between CS and FSE for ADG and feed conversion ratio in the finisher
      phase and overall, as well as total antioxidant capacity, SOD activity, uric
      acid, and antibody titers to NDV at d 21, as well as relative weights of thymus
      at d 42. In conclusion, dietary FSE supplementation enhanced nutrient
      digestibility and performance of broiler possibly by reducing oxidative stress
      and immune depression challenged by CS. 

PMID- 24864292
TI  - The effects of enzyme supplementation on performance and digestive parameters of
      broilers fed corn-soybean diets.
AB  - The study was performed to evaluate the effects of enzyme supplementation on
      performance and digestive parameters of broilers fed corn-soybean diets from 1 to
      21 d of age. A total of 480 one-day-old Cobb broilers were allocated to 1 of 4
      treatments, with 6 replicate pens per treatment and 20 birds per pen. The
      experiment consisted of a 2 * 2 factorial arrangement of treatments with 2
      dietary ME levels (high ME, energy 1, 12.13 MJ/kg or low ME, energy 2, 11.92
      MJ/kg) and 2 levels of supplemental enzyme (including xylanase, 1,800 IU/g, beta
      glucanase, 500 IU/g, and alpha-amylase, 800 U/g; 0 or 0.1% of diet). Enzyme
      supplementation had no effect on average daily weight gain, feed intake, and
      feed:gain. However, enzyme supplementation decreased the relative weight of the
      pancreas (d 7 and 21) in broilers fed the high ME diet. Low dietary ME level
      increased pancreatic lipase (d 7, P = 0.015), trypsin (d 14, P = 0.01; d 21, P =
      0.014), amylase (d 21, P = 0.027), and pepsin (d 7, P = 0.001; d 21, P = 0.042)
      activity, but reduced pancreatic lipase (d 14, P = 0.03; d 21, P = 0.004) and
      amylase (d 14, P = 0.027) activity. Enzyme supplementation resulted in an
      increase in pancreatic amylase (d 7, P = 0.023), trypsin (d 7, P = 0.02; d 21, P
      = 0.004), lipase (d 21, P = 0.001), pepsin (d 7, P = 0.001; d 14, P = 0.004; d
      21, P = 0.001), and maltase (d 14, P = 0.011, in ileum) activity. Moreover,
      broilers fed low dietary ME and enzyme supplementation diets had an increase in
      pancreatic lipase (d 21, P = 0.001) and pepsin (d 7, P = 0.001) activity. Low ME
      diets reduced jejunum villus height and jejunum and ileum crypt depth (d 7, 21).
      However, enzyme supplementation, especially enzyme supplementation in low ME
      diets, increased jejunum and ileum villus height and villus surface area. This
      suggested enzyme supplemented with low ME diet might be more effective to improve
      the activity of digestive enzymes and the absorptive capacity of the small
      intestine. 

PMID- 24864293
TI  - Effect of feeder space during the growing and laying periods and the rate of feed
      increase at the onset of lay on broiler breeder female reproductive function.
AB  - A study was conducted to examine how 2 feeder space allocations during the
      rearing period followed by 2 feeder space allocations after photostimulation and
      2 female feeding to peak programs (fast or slow) affected female broiler breeder
      reproductive performance and mortality. Sixteen pens of 76 breeder females each
      were equipped with either 4 tube feeders with a 132 cm circumference pan (7.0
      cm/female) or 6 feeders (10.4 cm/female) to 21 wk of age. Thereafter, 64 females
      were moved to breeding pens, photostimulated, and fed sex-separate from either 3
      (6.2 cm/female) or 5 (10.3 cm/female) feeders with either fast or slow feeding to
      peak feeding programs applied to complete a 2 * 2 * 2 factorial design. Seven
      males that were separately reared in a similar manner were added per pen.
      Individual female BW was determined at 6, 20, and 32 wk of age and BW uniformity
      assessed. Greater feeder space during rearing increased BW at 32 wk of age,
      whereas greater feeder space during lay or slow feeding to peak decreased BW at
      32 wk. There were no differences in BW uniformity. Hens from the 10.4 to 10.3
      cm/female combination produced a significantly greater number of eggs as compared
      with the 7.0 to 10.3 cm/female and 10.4 to 6.2 cm/female combinations with the
      7.0 to 6.2 cm/female combination intermediate. Percentage hen-day egg production
      of the 10.4 to 10.3 cm/female combination hens was significantly greater than all
      other combinations. Livability was improved in the 10.4 to 10.3 cm/female
      combination relative to the 7.0 to 10.3 cm/female combination with the others
      intermediate. The fast feeding to peak program increased yolk weight as well as
      yolk:albumen ratio at 28 and 30 wk of age, but egg weight did not differ. These
      data indicated that increased or decreased feeder space between the growing and
      laying periods did not affect broiler breeder female BW, uniformity, egg weight,
      fertility, or hatchability. The 10.3 cm/female laying feeder space exhibited the
      best hen-day egg production in combination with 10.4 cm/pullet rearing but not
      with 7.0 cm/pullet rearing space. In a similar manner, hen mortality was greater
      in the 7.0 to 10.3 cm/female feeder space combination that the 10.4 to 10.3
      cm/female combination. 

PMID- 24864295
TI  - Enrofloxacin against Escherichia coli in turkeys: which treatment scheme is
      effective?
AB  - The efficacy of enrofloxacin (ENRO) was evaluated against multidrug-resistant
      avian pathogenic Escherichia coli correlating the minimum inhibitory
      concentrations (MIC) of 235 E. coli field strains with its pharmacokinetics (PK)
      in 50 healthy turkeys (5 groups) with a PK/pharmacodynamic approach. The
      treatments were as follows: a) single oral gavage and b) single subcutaneous (SC)
      treatment at the recommended dose of 10 mg/kg; c) single oral gavage, d) 5 d of
      10-h pulsed water medication, and e) 5 d of 24-h continuous water medication at
      the doubled dose of 20 mg/kg. Blood samples were collected at established times
      over 24 h. Plasma was analyzed using a liquid chromatography tandem mass
      spectrometry method that was validated in house. A monocompartmental and a
      noncompartmental model were applied to the data to obtain the PK results. After
      gavage administration, the mean maximum concentration Cmax/MIC50 and area under
      the curve AUC0-24/MIC50 ratios were, respectively, 3.07 +/- 0.62 and 7.01 +/-
      1.03 and 25.48 +/- 3.04 and 57.2 +/- 3.73 for the 10 and 20 mg/kg doses,
      respectively. After SC administration of 10 mg/kg, Cmax/MIC50 and AUC0-24/MIC50
      ratios were 3.45 +/- 0.75 and 33.96 +/- 7.46, respectively. After the
      administration of 10-h pulsed or 24-h continuous medicated water at 20 mg/kg,
      lower values of Cmax/MIC50 (10-h pulsed: 3.45 +/- 0.7; 24-h continuous: 3.05 +/-
      0.48) and AUC0-24/MIC50 (10-h pulsed: 42.42 +/- 6.17; 24-h continuous: 53.32 +/-
      5.55) were obtained. Based on these results, the European Union-recommended
      dosage of 10 mg/kg seems ineffective to achieve adequate drug plasma
      concentrations and even the 20 mg/kg by 10 h pulsed or continuous medicated water
      administration did not reach completely efficacious concentrations in plasma
      against colibacillosis. Although the results obtained were not completely
      encouraging, the medicated water should preferably be provided continuously. To
      conclude about the efficacy of ENRO treatment against colibacillosis, target
      tissue concentration should be extensively considered. 

PMID- 24864294
TI  - Lysine partitioning in broiler breeders is not affected by energy or protein
      intake when fed at current industry levels.
AB  - A study was conducted to determine the effects of dietary energy and protein
      intake on the partitioning of lysine in broiler breeder hens. One hundred twenty
      six broiler breeders were randomly assigned to 1 of 6 dietary treatments in a 2
      (390, 450 kcal/d) * 3 (22, 24, 26 g of CP/d) fashion. Thirty-six hens were
      administered a daily oral dose of 15 mg of (15)N-Lys for a period of 2 wk or
      until first egg. After the 2-wk enrichment period, no isotopes were given for 2
      d. After 2 d, a daily oral dose of 15 mg of (2)D4-Lys was administered until the
      2nd, 3rd, and 4th egg (saved) after the initial (2)D4-Lys was given, at which
      point pectoralis muscle was sampled. Weeks 25, 29, and 45 were assessed. Isotopic
      enrichment of pectoralis muscle, egg yolk, and albumen was determined via gas
      chromatography-mass spectrometry. The (15)N-Lys was intended to represent
      endogenous lysine, whereas the (2)D4-Lys was intended to represent dietary
      lysine. Greater than 78% of all labeled lysine ((15)N and (2)D4-Lys) was found in
      breast muscle. Endogenous muscle was the main source of lysine for yolk formation
      at wk 25 and 45. Diet was the main source of lysine for albumen formation at wk
      25 and 29. A consistent decrease in the (15)N-Lys in breast muscle from the 2nd
      to the 3rd egg was observed, while also seeing an increase in the (15)N-Lys in
      the egg from the 3rd to the 4th egg. No difference in the partitioning of lysine
      was determined by energy or protein intake at levels typical for the current
      poultry industry. Rather, age, and possibly rate of production, appear to be the
      main drivers of lysine partitioning in the broiler breeder hen. 

PMID- 24864296
TI  - Effects of a dietary antioxidant blend and vitamin E on growth performance,
      oxidative status, and meat quality in broiler chickens fed a diet high in
      oxidants.
AB  - The aim of the study was to determine the effects of a dietary antioxidant blend
      (AB) and vitamin E on performance, oxidative status, and meat quality. Cobb 500
      male broilers (n = 1,200, d 0) were randomly distributed into 6 treatments with
      10 replicate pens. Treatments included 1) HO: high oxidant diet, vitamin E at 10
      IU/kg, 3% oxidized soybean oil, 3% polyunsaturated fatty acid (PUFA) source; 2)
      VE: the HO diet with vitamin E at 200 IU/kg; 3) AOX: the HO diet with AB at 135
      mg/kg; 4) VE+AOX: the HO diet with vitamin E at 200 IU/kg and AB at 135 mg/kg; 5)
      SC: standard control; and 6) PC: positive control, the SC diet with AB at 135
      mg/kg. From d 0 through d 21, high oxidant diet treatment birds had greater BW,
      ADG, and ADFI than the SC birds; the AOX birds had better G:F on d 10 and 42, and
      from d 0 to 42 than SC birds (P < 0.05). The plasma TBA reactive substance level
      was lower in the AOX birds than the VE treatment birds in all phases (P < 0.05).
      High oxidant diet treatment birds had greater alpha-1-acid glycoprotein levels on
      d 10 than SC and PC birds (P < 0.05). The AOX, PC, and SC birds had a greater
      level of uric acid than the HO and VE+AOX birds on d 10. Superoxide dismutase
      expression in the liver was less with the HO treatment compared with the SC
      treatment on d 7 (P < 0.05). The vitamin E concentration in the breast muscle was
      greatest in the VE birds, whereas vitamin A concentration was greater in the PC
      birds compared with the SC birds on d 21 (P < 0.05). Compared with VE and AOX,
      the HO treatment had greater drip loss (P < 0.05). In conclusion, dietary
      addition of AOX was effective in improving growth, moderately restored the whole
      body antioxidant capability, and reduced drip loss. 

PMID- 24864297
TI  - How adolescents learn about risk perception and behavior in regards to alcohol
      use in light of social learning theory: a qualitative study in Bogota, Colombia.
AB  - BACKGROUND: In Colombia, the use of alcohol is one of the main risky behaviors
      carried out by adolescents, given that alcohol is the principal drug of abuse in
      this age group. Understanding how adolescents learn about risk and behavior is
      important in developing effective prevention programs. The Theory of Social
      learning underlines the importance of social interaction in the learning process.
      It suggests that learning can occur in three ways: a live model in which a person
      is enacting the desired behavior, verbal instruction when the desired behavior is
      described, and symbolic learning in which modeling occurs by influence of the
      media. This study explores these three forms of learning in the perception of
      risk and behavior related to the use of alcohol in a group of students between 12
      and 14 years of age in Bogota, Colombia. MATERIALS AND METHODS: This is a
      qualitative research study, which is part of a larger study exploring the social
      representations of risk and alcohol use in adolescents and their communities. The
      sample group included 160 students from two middle schools (7th and 8th graders)
      in Bogota, Colombia. Six sessions of participant observation, 12 semi-structured
      interviews, and 12 focus group discussions were conducted for data collection.
      Data were analyzed using the Atlas ti software (V7.0) (ATLAS.ti Scientific
      Software Development GmbH, London, UK), and categories of analysis were developed
      using a framework analysis approach. RESULTS: Adolescents can identify several
      risks related to the use of alcohol, which for the most part, appear to have been
      learned through verbal instruction. However, this risk recognition does not
      appear to correlate with their behavior. Parental modeling and messages conveyed
      by the media represent two other significant sources of learning that are
      constantly contradicting the messages relayed through verbal instruction and
      correlate to a greater extent with adolescent behavior. CONCLUSION: The three
      different forms of learning described by Social Learning Theory play a
      significant role in the construction of risk perception and behavior in
      adolescents. This underlines the necessity of consciously evaluating how examples
      set by adults as well as the ideas expressed by the media influence adolescents'
      attitudes and behavior, ensuring that these do not directly contradict and
      ultimately obliterate the messages we are constantly trying to convey to this age
      group.

PMID- 24864298
TI  - Female adolescents' perspective about reproductive health education needs: a
      mixed methods study with explanatory sequential design.
AB  - BACKGROUND: One of the most important and basic needs of adolescent girls is
      reproductive health services and education, which is different from that required
      by adults. OBJECTIVES: The aim of this study was to determine reproductive health
      education needs from the perspective of adolescent girls living in urban and
      rural areas, as well as to explore adolescents' understanding of reproductive
      health needs. SUBJECTS: The first phase was a cross-sectional study conducted on
      1274 female adolescents. In the second phase, 77 girls in the form of 11 groups
      participated in focused group discussions. METHODS: This sequential explanatory
      mixed methods study using follow-up variants was conducted in two phases.
      Questionnaires, including items on socio-demographic characteristics and
      reproductive health needs from adolescents' perspectives, were completed using
      the self-administered method. RESULTS: The quantitative results of the study
      revealed city and village girls' perspectives on reproductive health education
      needs. These results showed that village adolescents were nearly 1.5-2 times more
      in favor of a same sex counselor, reproductive health group education, and the
      need for sexual health education than city adolescents. A review of the
      transcripts of the qualitative phase led to the extraction of two themes
      including the characteristics of the reproductive health educator and priorities
      of reproductive health education, which explains the adolescent girls'
      understanding of reproductive health education needs. CONCLUSION: The findings of
      this study confirm the importance of determining reproductive health education
      needs from the perspective of adolescent girls. The present study shows how a
      sequential mixed design can be used for a better understanding of reproductive
      health needs of adolescent girls. The results of this study can be used in health
      research, education, policy making, and planning associated with adolescent
      health.

PMID- 24864299
TI  - Nutrition and physical activity during the transition from adolescence to
      adulthood: further research is warranted.
AB  - The transition from adolescence to adulthood is associated with many physical,
      social, and psychological changes. In addition, adolescents also have to deal
      with structural changes. An example of one such structural change is the
      transition from school to university or to other vocational establishments.
      Structural changes can also entail changes in overall framework conditions and
      daily life patterns and thus also in dietary habits and physical activity levels.
      The aim of the present paper was to draw attention to the research deficit in
      this area with the help of the results of our analyses. The results show that
      significant changes take place as a consequence of the transition from school to
      a vocational establishment. However, our analyses could not identify the exact
      catalysts and the time framework of these changes. In this respect, further
      research is urgently warranted.

PMID- 24864301
TI  - Statistical inference of regulatory networks for circadian regulation.
AB  - We assess the accuracy of various state-of-the-art statistics and machine
      learning methods for reconstructing gene and protein regulatory networks in the
      context of circadian regulation. Our study draws on the increasing availability
      of gene expression and protein concentration time series for key circadian clock
      components in Arabidopsis thaliana. In addition, gene expression and protein
      concentration time series are simulated from a recently published regulatory
      network of the circadian clock in A. thaliana, in which protein and gene
      interactions are described by a Markov jump process based on Michaelis-Menten
      kinetics. We closely follow recent experimental protocols, including the
      entrainment of seedlings to different light-dark cycles and the knock-out of
      various key regulatory genes. Our study provides relative network reconstruction
      accuracy scores for a critical comparative performance evaluation, and sheds
      light on a series of highly relevant questions: it quantifies the influence of
      systematically missing values related to unknown protein concentrations and mRNA
      transcription rates, it investigates the dependence of the performance on the
      network topology and the degree of recurrency, it provides deeper insight into
      when and why non-linear methods fail to outperform linear ones, it offers
      improved guidelines on parameter settings in different inference procedures, and
      it suggests new hypotheses about the structure of the central circadian gene
      regulatory network in A. thaliana.

PMID- 24864302
TI  - Applying shrinkage variance estimators to the TOST test in high dimensional
      settings.
AB  - BACKGROUND: Identifying differentially expressed genes has been an important and
      widely used approach to investigate gene functions and molecular mechanisms. A
      related issue that has drawn much less attention but is equally important is the
      identification of constantly expressed genes across different conditions. A
      common practice is to treat genes that are not significantly differentially
      expressed as significantly equivalently expressed. Such naive practice often
      leads to large false discovery rate and low power. The more appropriate way for
      identifying constantly expressed genes should be conducting high dimensional
      statistical equivalence tests. A well-known equivalence test, the two one-sided
      tests (TOST), can be used for this purpose. However, due to the small sample
      sizes often associated with genomics data, the variance estimator in the TOST
      test could be unstable. Hence it would be fitting to examine the application of
      shrinkage variance estimators to the TOST test in high dimensional settings.
      RESULT: In this paper, we study the effect of shrinking the variance estimators
      in the TOST test in high dimensional settings through simulation studies. In
      addition, we derive analytic formulas for the p-value of the resultant shrinkage
      variance TOST test and apply it to a real data set.

PMID- 24864300
TI  - Opinion paper on utility of point-of-care biomarkers in the emergency department
      pathways decision making.
AB  - Overcrowding of the emergency department (ED) is rapidly becoming a global
      challenge and a major source of concern for emergency physicians. The evaluation
      of cardiac biomarkers is critical for confirming diagnoses and expediting
      treatment decisions to reduce overcrowding, however, physicians currently face
      the dilemma of choosing between slow and accurate central-based laboratory tests,
      or faster but imprecise assays. With improvements in technology, point-of-care
      testing (POCT) systems facilitate the efficient and high-throughput evaluation of
      biomarkers, such as troponin (cTn), brain natriuretic peptide (BNP) and
      neutrophil gelatinase-associated lipocalin (NGAL). In this context, POCT may help
      ED physicians to confirm a diagnosis of conditions, such as acute coronary
      syndrome, heart failure or kidney damage. Compared with classic laboratory
      methods, the use of cTn, BNP, and NGAL POCT has shown comparable sensitivity,
      specificity and failure rate, but with the potential to provide prompt and
      accurate diagnosis, shorten hospital stay, and alleviate the burden on the ED.
      Despite this potential, the full advantages of rapid delivery results will only
      be reached if POCT is implemented within hospital standardized procedures and ED
      staff receive appropriate training.

PMID- 24864303
TI  - Using the theory of added-variable plot for linear mixed models to decompose
      genetic effects in family data.
AB  - Effective analytical tools are highly desirable for data analysis and for making
      the biological link between genotypic and phenotypic measures. In family data it
      is important to reconcile the methods that explain the phenotypic variability
      through fixed genetic effects and ones that estimate variance components using
      classical heritability methods. Thus, in this paper, we propose a method based on
      added-variable plot for polygenic linear mixed models applied to genome wide
      association studies in family-based designs. Our goal is to be able to
      discriminate genetic predictor variables in effects due to random polygenic and
      residual components. We also propose an index to detect influential families for
      each predictor variable identified with genetic effect. We assess the performance
      of our proposed method using our own family simulated data and the Genetic
      Analysis Workshop 17 family simulated data.

PMID- 24864304
TI  - Dietary switch reveals fast coordinated gene expression changes in Drosophila
      melanogaster.
AB  - Dietary restriction (DR) reduces age-specific mortality and increases lifespan in
      many organisms. DR elicits a large number of physiological changes, however many
      are undoubtedly not related to longevity. Whole-genome gene expression studies
      have typically revealed hundreds to thousands of differentially expressed genes
      in response to DR, and a key open question is which subset of genes mediates
      longevity. Here we performed transcriptional profiling of fruit flies in a
      closely spaced time series immediately following a switch to the DR regime and
      identified four patterns of transcriptional dynamics. Most informatively we find
      144 genes rapidly switched to the same level observed in the DR cohort and are
      hence strong candidates as proximal mediators of reduced mortality upon DR. This
      class was enriched for genes involved in carbohydrate and fatty acid metabolism.
      Folate biosynthesis was the only pathway enriched for gene up- regulated upon DR.
      Four among the down-regulated genes are involved in key regulatory steps within
      the pentose phosphate pathway, which has been previously associated with lifespan
      extension in Drosophila. Combined analysis of dietary switch with whole-genome
      time-course profiling can identify transcriptional responses that are closely
      associated with and perhaps causal to longevity assurance conferred by dietary
      restriction.

PMID- 24864305
TI  - Current implantable cardioverter-defibrillator programming in Europe: the results
      of the European Heart Rhythm Association survey.
AB  - The purpose of this European Heart Rhythm Association (EHRA) survey was to
      examine the current practice on the choice of implantable cardioverter
      defibrillator (ICD) type, use of defibrillation testing, and ICD programming for
      detection and therapy of ventricular arrhythmias. In accordance with recent
      guidelines and the results of observational studies, the majority of EHRA
      research network centres reported a high utilization rate of dual-chamber ICDs in
      the presence of symptomatic and asymptomatic sinus node dysfunction,
      biventricular ICD in high-degree atrioventricular block and QRS duration <120 ms,
      and a limited use of defibrillation testing either in primary and secondary
      prevention settings. Activation of the long ventricular tachycardia (VT)
      detection window, slow VT zone, antitachycardia pacing before shock for slow and
      fast VT, and atrial tachyarrhythmia discrimination were considered useful in ICD
      programming for the majority of patients. 

PMID- 24864307
TI  - Perceived environmental barriers to outdoor mobility and feelings of loneliness
      among community-dwelling older people.
AB  - BACKGROUND: We examined the association between perceived environmental barriers
      to outdoor mobility and loneliness among community-dwelling older people. In
      addition, we studied whether walking difficulties and autonomy in participation
      outdoors affected this association. METHODS: Cross-sectional analyses of face-to
      face home interview data with 848 people aged 75-90 years (mean age: 80.1 years;
      62% women) gathered within the "Life-Space Mobility in Old Age" (LISPE) project.
      Self-reports of loneliness, environmental barriers to outdoor mobility, and
      difficulties in walking 2 km were obtained with structured questionnaires.
      Autonomy in participation outdoors was assessed with the "Impact on Participation
      and Autonomy" questionnaire. RESULTS: Altogether, 28% of participants reported
      experiencing loneliness sometimes or often. These participants also reported more
      difficulties in walking 2 km, restricted autonomy in participation outdoors, and
      more environmental barriers to outdoor mobility than people not experiencing
      loneliness. Snowy and icy winter conditions (odds ratio: 1.59 [95% confidence
      interval: 1.15-2.20]), long distances to services (odds ratio: 1.57 [1.00-2.46]),
      and hills in the nearby environment (odds ratio: 1.49 [1.05-2.12]) significantly
      increased the odds for loneliness, even after adjustments for walking
      difficulties, autonomy in participation outdoors, perceived financial situation,
      living alone, and health. Path modeling revealed that environmental barriers
      increased loneliness either through direct association or indirectly through
      restricted autonomy in participation outdoors. CONCLUSIONS: Prospective studies
      should investigate whether removing environmental barriers to outdoor mobility
      improves autonomy in participation outdoors and alleviates loneliness among older
      people.

PMID- 24864306
TI  - Advanced age, cardiovascular risk burden, and timed up and go test performance in
      Parkinson disease.
AB  - BACKGROUND: Cardiovascular comorbidities are a known risk factor for impaired
      mobility in elderly individuals. Motor impairments in Parkinson disease are
      conventionally ascribed to nigrostriatal dopaminergic denervation although
      progressive gait and balance impairments become more common with aging and often
      show limited response to dopaminergic replacement therapies. METHODS: We explored
      the association between elevated cardiovascular risk factors and performance on
      the Timed Up and Go test in cross-sectional of Parkinson disease subjects (n =
      83). Cardiovascular risk factor status was estimated using the Framingham General
      Cardiovascular Disease risk-scoring algorithm in order to dichotomize the cohort
      into those with and without elevated modifiable cardiovascular risk compared with
      normative scores for age and gender. All subjects underwent clinical and
      neuroimaging evaluations including a 3-m Timed Up and Go test,
      [(11)C]dihydrotetrabenazine positron emission tomography imaging to estimate
      nigrostriatal dopamine terminal loss, and an magnetic resonance imaging
      assessment of leukoaraiosis. A similar analysis was performed in 49 healthy
      controls. RESULTS: After adjusting for disease duration, leukoaraiosis, and
      nigrostriatal dopaminergic denervation, Parkinson disease subjects with elevated
      Framingham risk scores (n = 61) displayed slower Timed Up and Go test performance
      (beta = 1.86, t = 2.41, p = .018) compared with subjects with normal range
      Framingham risk scores (n = 22). When age >=65 was added to the model in a post
      hoc analysis, the strength of effect seen with older age (beta = 1.51, t = 2.44,
      p = .017) was similar to that of elevated Framingham risk scoring (beta = 1.87, t
      = 2.51, p = .014). In a multivariable regression model studying the healthy
      control population, advanced age (t = 2.15, p = .037) was a significant predictor
      of Timed Up and Go speed though striatal [(11)C]dihydrotetrabenazine (t = -1.30,
      p = .19) and elevated Framingham risk scores (t = 1.32, p = .19) were not.
      CONCLUSIONS: Modifiable cardiovascular risk factors and older age may
      independently exacerbate balance-related disability in Parkinson disease and may
      exert additive or synergistic pathological effects. The pathophysiology of these
      impairments cannot be explained completely by nigrostriatal dopaminergic
      denervation or leukoaraiosis burden and may relate to systemic factors seen with
      accelerated aging.

PMID- 24864308
TI  - Prognostic implications of microvascular and macrovascular abnormalities in older
      adults: cardiovascular health study.
AB  - BACKGROUND: Microvascular and macrovascular abnormalities are frequently found on
      noninvasive tests performed in older adults. Their prognostic implications on
      disability and life expectancy have not been collectively assessed. METHODS: This
      prospective study included 2,452 adults (mean age: 79.5 years) with available
      measures of microvascular (brain, retina, kidney) and macrovascular abnormalities
      (brain, carotid, coronary, peripheral artery) in the Cardiovascular Health Study.
      The burden of microvascular and macrovascular abnormalities was examined in
      relation to total, activity-of-daily-living disability-free, and severe
      disability-free life expectancies in the next 10 years (1999-2009). RESULTS: At
      75 years, individuals with low burden of both abnormalities lived, on average,
      8.71 years (95% confidence interval: 8.29, 9.12) of which 7.67 years (7.16, 8.17)
      were without disability. In comparison, individuals with high burden of both
      abnormalities had shortest total life expectancy (6.95 years [6.52, 7.37]; p <
      .001) and disability-free life expectancy (5.60 years [5.10, 6.11]; p < .001).
      Although total life expectancy was similarly reduced for those with high burden
      of either type of abnormalities (microvascular: 7.96 years [7.50, 8.42] vs
      macrovascular: 8.25 years [7.80, 8.70]; p = .10), microvascular abnormalities
      seemed to have larger impact than macrovascular abnormalities on disability-free
      life expectancy (6.45 years [5.90, 6.99] vs 6.96 years [6.43, 7.48]; p = .016).
      These results were consistent for severe disability-free life expectancy and in
      individuals without clinical cardiovascular disease. CONCLUSIONS: Considering
      both microvascular and macrovascular abnormalities from multiple noninvasive
      tests may provide additional prognostic information on how older adults spend
      their remaining life. Optimal clinical use of this information remains to be
      determined.

PMID- 24864309
TI  - What cost mitochondria? The maintenance of functional mitochondrial DNA within
      and across generations.
AB  - The peculiar biology of mitochondrial DNA (mtDNA) potentially has detrimental
      consequences for organismal health and lifespan. Typically, eukaryotic cells
      contain multiple mitochondria, each with multiple mtDNA genomes. The high copy
      number of mtDNA implies that selection on mtDNA functionality is relaxed.
      Furthermore, because mtDNA replication is not strictly regulated, within-cell
      selection may favour mtDNA variants with a replication advantage, but a
      deleterious effect on cell fitness. The opportunities for selfish mtDNA mutations
      to spread are restricted by various organism-level adaptations, such as
      uniparental transmission, germline mtDNA bottlenecks, germline selection and,
      during somatic growth, regular alternation between fusion and fission of
      mitochondria. These mechanisms are all hypothesized to maintain functional mtDNA.
      However, the strength of selection for maintenance of functional mtDNA
      progressively declines with age, resulting in age-related diseases. Furthermore,
      organismal adaptations that most probably evolved to restrict the opportunities
      for selfish mtDNA create secondary problems. Owing to predominantly maternal
      mtDNA transmission, recombination among mtDNA from different individuals is
      highly restricted or absent, reducing the scope for repair. Moreover, maternal
      inheritance precludes selection against mtDNA variants with male-specific
      effects. We finish by discussing the consequences of life-history differences
      among taxa with respect to mtDNA evolution and make a case for the use of
      microorganisms to experimentally manipulate levels of selection. 

PMID- 24864311
TI  - The costs of being male: are there sex-specific effects of uniparental
      mitochondrial inheritance?
AB  - Eukaryotic cells typically contain numerous mitochondria, each with multiple
      copies of their own genome, the mtDNA. Uniparental transmission of mitochondria,
      usually via the mother, prevents the mixing of mtDNA from different individuals.
      While on the one hand, this should resolve the potential for selection for fast
      replicating mtDNA variants that reduce organismal fitness, maternal inheritance
      will, in theory, come with another set of problems that are specifically relevant
      to males. Maternal inheritance implies that the mitochondrial genome is never
      transmitted through males, and thus selection can target only the mtDNA sequence
      when carried by females. A consequence is that mtDNA mutations that confer male
      biased phenotypic expression will be prone to evade selection, and accumulate.
      Here, we review the evidence from the ecological, evolutionary and medical
      literature for male specificity of mtDNA mutations affecting fertility, health
      and ageing. While such effects have been discovered experimentally in the
      laboratory, their relevance to natural populations--including the human
      population--remains unclear. We suggest that the existence of male expression
      biased mtDNA mutations is likely to be a broad phenomenon, but that these
      mutations remain cryptic owing to the presence of counter-adapted nuclear
      compensatory modifier mutations, which offset their deleterious effects.

PMID- 24864312
TI  - Quality matters: how does mitochondrial network dynamics and quality control
      impact on mtDNA integrity?
AB  - Mammalian mtDNA encodes for 13 core proteins of oxidative phosphorylation.
      Mitochondrial DNA mutations and deletions cause severe myopathies and
      neuromuscular diseases. Thus, the integrity of mtDNA is pivotal for cell survival
      and health of the organism. We here discuss the possible impact of mitochondrial
      fusion and fission on mtDNA maintenance as well as positive and negative
      selection processes. Our focus is centred on the important question of how the
      quality of mtDNA nucleoids can be assured when selection and mitochondrial
      quality control works on functional and physiological phenotypes constituted by
      oxidative phosphorylation proteins. The organelle control theory suggests a link
      between phenotype and nucleoid genotype. This is discussed in the light of new
      results presented here showing that mitochondrial transcription factor
      A/nucleoids are restricted in their intramitochondrial mobility and probably have
      a limited sphere of influence. Together with recent published work on
      mitochondrial and mtDNA heteroplasmy dynamics, these data suggest first, that
      single mitochondria might well be internally heterogeneous and second, that
      nucleoid genotypes might be linked to local phenotypes (although the link might
      often be leaky). We discuss how random or site-specific mitochondrial fission can
      isolate dysfunctional parts and enable their elimination by mitophagy, stressing
      the importance of fission in the process of mtDNA quality control. The role of
      fusion is more multifaceted and less understood in this context, but the mixing
      and equilibration of matrix content might be one of its important functions. 

PMID- 24864310
TI  - Control of mitochondrial integrity in ageing and disease.
AB  - Various molecular and cellular pathways are active in eukaryotes to control the
      quality and integrity of mitochondria. These pathways are involved in keeping a
      'healthy' population of this essential organelle during the lifetime of the
      organism. Quality control (QC) systems counteract processes that lead to
      organellar dysfunction manifesting as degenerative diseases and ageing. We
      discuss disease- and ageing-related pathways involved in mitochondrial QC: mtDNA
      repair and reorganization, regeneration of oxidized amino acids, refolding and
      degradation of severely damaged proteins, degradation of whole mitochondria by
      mitophagy and finally programmed cell death. The control of the integrity of
      mtDNA and regulation of its expression is essential to remodel single proteins as
      well as mitochondrial complexes that determine mitochondrial functions. The
      redundancy of components, such as proteases, and the hierarchies of the QC raise
      questions about crosstalk between systems and their precise regulation. The
      understanding of the underlying mechanisms on the genomic, proteomic, organellar
      and cellular levels holds the key for the development of interventions for
      mitochondrial dysfunctions, degenerative processes, ageing and age-related
      diseases resulting from impairments of mitochondria. 

PMID- 24864313
TI  - Mitonuclear interactions: evolutionary consequences over multiple biological
      scales.
AB  - Fundamental biological processes hinge on coordinated interactions between genes
      spanning two obligate genomes--mitochondrial and nuclear. These interactions are
      key to complex life, and allelic variation that accumulates and persists at the
      loci embroiled in such intergenomic interactions should therefore be subjected to
      intense selection to maintain integrity of the mitochondrial electron transport
      system. Here, we compile evidence that suggests that mitochondrial-nuclear
      (mitonuclear) allelic interactions are evolutionarily significant modulators of
      the expression of key health-related and life-history phenotypes, across several
      biological scales--within species (intra- and interpopulational) and between
      species. We then introduce a new frontier for the study of mitonuclear
      interactions--those that occur within individuals, and are fuelled by the mtDNA
      heteroplasmy and the existence of nuclear-encoded mitochondrial gene duplicates
      and isoforms. Empirical evidence supports the idea of high-resolution tissue- and
      environment-specific modulation of intraindividual mitonuclear interactions.
      Predicting the penetrance, severity and expression patterns of mtDNA-induced
      mitochondrial diseases remains a conundrum. We contend that a deeper
      understanding of the dynamics and ramifications of mitonuclear interactions,
      across all biological levels, will provide key insights that tangibly advance our
      understanding, not only of core evolutionary processes, but also of the complex
      genetics underlying human mitochondrial disease.

PMID- 24864314
TI  - How to deal with oxygen radicals stemming from mitochondrial fatty acid
      oxidation.
AB  - Oxygen radical formation in mitochondria is an incompletely understood attribute
      of eukaryotic cells. Recently, a kinetic model was proposed, in which the ratio
      between electrons entering the respiratory chain via FADH2 or NADH determines
      radical formation. During glucose breakdown, the ratio is low; during fatty acid
      breakdown, the ratio is high (the ratio increasing--asymptotically--with fatty
      acid length to 0.5, when compared with 0.2 for glucose). Thus, fatty acid
      oxidation would generate higher levels of radical formation. As a result,
      breakdown of fatty acids, performed without generation of extra FADH2 in
      mitochondria, could be beneficial for the cell, especially in the case of long
      and very long chained ones. This possibly has been a major factor in the
      evolution of peroxisomes. Increased radical formation, as proposed by the model,
      can also shed light on the lack of neuronal fatty acid oxidation and tells us
      about hurdles during early eukaryotic evolution. We specifically focus on
      extending and discussing the model in light of recent publications and findings.

PMID- 24864315
TI  - Does autophagy mediate age-dependent effect of dietary restriction responses in
      the filamentous fungus Podospora anserina?
AB  - Autophagy is a well-conserved catabolic process, involving the degradation of a
      cell's own components through the lysosomal/vacuolar machinery. Autophagy is
      typically induced by nutrient starvation and has a role in nutrient recycling,
      cellular differentiation, degradation and programmed cell death. Another common
      response in eukaryotes is the extension of lifespan through dietary restriction
      (DR). We studied a link between DR and autophagy in the filamentous fungus
      Podospora anserina, a multicellular model organism for ageing studies and
      mitochondrial deterioration. While both carbon and nitrogen restriction extends
      lifespan in P. anserina, the size of the effect varied with the amount and type
      of restricted nutrient. Natural genetic variation for the DR response exists.
      Whereas a switch to carbon restriction up to halfway through the lifetime
      resulted in extreme lifespan extension for wild-type P. anserina, all autophagy
      deficient strains had a shorter time window in which ageing could be delayed by
      DR. Under nitrogen limitation, only PaAtg1 and PaAtg8 mediate the effect of
      lifespan extension; the other autophagy-deficient mutants PaPspA and PaUth1 had a
      similar response as wild-type. Our results thus show that the ageing process
      impinges on the DR response and that this at least in part involves the genetic
      regulation of autophagy. 

PMID- 24864316
TI  - Regular bottlenecks and restrictions to somatic fusion prevent the accumulation
      of mitochondrial defects in Neurospora.
AB  - The replication and segregation of multi-copy mitochondrial DNA (mtDNA) are not
      under strict control of the nuclear DNA. Within-cell selection may thus favour
      variants with an intracellular selective advantage but a detrimental effect on
      cell fitness. High relatedness among the mtDNA variants of an individual is
      predicted to disfavour such deleterious selfish genetic elements, but
      experimental evidence for this hypothesis is scarce. We studied the effect of
      mtDNA relatedness on the opportunities for suppressive mtDNA variants in the
      fungus Neurospora carrying the mitochondrial mutator plasmid pKALILO. During
      growth, this plasmid integrates into the mitochondrial genome, generating
      suppressive mtDNA variants. These mtDNA variants gradually replace the wild-type
      mtDNA, ultimately culminating in growth arrest and death. We show that regular
      sequestration of mtDNA variation is required for effective selection against
      suppressive mtDNA variants. First, bottlenecks in the number of mtDNA copies from
      which a 'Kalilo' culture started significantly increased the maximum lifespan and
      variation in lifespan among cultures. Second, restrictions to somatic fusion
      among fungal individuals, either by using anastomosis-deficient mutants or by
      generating allotype diversity, prevented the accumulation of suppressive mtDNA
      variants. We discuss the implications of these results for the somatic
      accumulation of mitochondrial defects during ageing. 

PMID- 24864318
TI  - Neutron metrology laboratory facility simulation.
AB  - The Neutron Low Scattering Laboratory in Brazil has been completely rebuilt.
      Evaluation of air attenuation parameters and neutron component scattering in the
      room was done using Monte Carlo simulation code. Neutron fields produced by
      referenced neutron source were used to calculate neutron scattering and air
      attenuation. 

PMID- 24864319
TI  - A Balancing Act: Experiences of Nurses and Physicians When Making End-of-Life
      Decisions in Intensive Care Units.
AB  - The purpose of this qualitative, descriptive study was to describe end-of-life
      decision-making experiences as understood by critical care nurses and physicians
      in intensive care units (ICUs). A purposive sample of seven nurses and four
      physicians from a large teaching hospital were interviewed. Grounded theory
      analysis revealed the core category of "end-of-life decision making as a
      balancing act." Three interacting subthemes were identified: emotional
      responsiveness, professional roles and responsibilities, and intentional
      communication and collaboration. Balancing factors included a team approach,
      shared goals, understanding the perspectives of those involved, and knowing your
      own beliefs. In contrast, feeling powerless, difficult family dynamics, and
      recognition of suffering caused an imbalance. When balance was achieved during
      end-of-life decision making, nurses and physicians described positive end-of-life
      experiences. The consequence of an imbalance during an end-of-life decision
      making experience was moral distress. Practice recommendations include
      development of support interventions for nurses and physicians involved in end-of
      life decision making and further research to test interventions aimed at
      improving communication and collaboration. 

PMID- 24864317
TI  - The road to rack and ruin: selecting deleterious mitochondrial DNA variants.
AB  - Mitochondria constitute the major energy-producing compartment of the eukaryotic
      cell. These organelles contain many molecules of DNA that contribute only a
      handful of proteins required for energy production. Mutations in the DNA of
      mitochondria were identified as a cause of human disease a quarter of a century
      ago, and they have subsequently been implicated in ageing. The process whereby
      deleterious variants come to dominate a cell, tissue or human is the subject of
      debate. It is likely to involve multiple, often competing, factors, as selection
      pressures on mitochondrial DNA can be both indirect and intermittent, and are
      subjected to rapid change. Here, we assess the different models and the prospects
      for preventing the accumulation of deleterious mitochondrial DNA variants with
      time. 

PMID- 24864320
TI  - Patients' Experiences of Sexual Activity Following Myocardial Ischemia.
AB  - The purpose of this article is to describe patients' experiences of sexual
      activity after suffering myocardial ischemia. We conducted semi-structured
      qualitative interviews with people who had suffered myocardial ischemia in the
      last 6 to 24 months before the interview. We used maximum variation sampling
      method. After reaching theoretical saturation, a 19-informants sample was formed.
      Data were analyzed using the Giorgi method. Four themes were identified: "sexual
      activity becomes different," "determinants of the return to sexual activity,"
      "how sexual activity ought to be," and "sexual information received." Patients
      showed a decrease both in frequency and desire for sexual activity influenced by
      fear of sexual activity and health care professionals' recommendations. These
      recommendations were about "avoiding sexuality at the beginning" and conducting
      "sexual activity without overdoing it." Health care professionals should educate
      patients about the right time to resume sexual activity. Nurses can help patients
      to deal with fears related to sexual activity. 

PMID- 24864321
TI  - Exploring staff perceptions on the role of physical environment in dementia care
      setting.
AB  - This study explored staff perceptions of the role of physical environment in
      dementia care facilities in affecting resident's behaviors and staff care
      practice. We conducted focus groups with staff (n = 15) in two purposely selected
      care facilities in Vancouver, Canada. Focus group participants included nurses,
      care aides, recreation staff, administrative staff, and family. Data analysis
      revealed two themes: (a) a supportive physical environment contributes positively
      to both quality of staff care interaction and residents' quality of life and (b)
      an unsupportive physical environment contributes negatively to residents' quality
      of life and thereby makes the work of staff more challenging. The staff
      participants collectively viewed that comfort, familiarity, and an organized
      space were important therapeutic resources for supporting the well-being of
      residents. Certain behaviors of residents were influenced by poor environmental
      factors, including stimulation overload, safety risks, wayfinding challenge, and
      rushed care This study demonstrates the complex interrelationships among the
      dementia care setting's physical environment, staff experiences, and residents'
      quality of life. 

PMID- 24864322
TI  - A prolonged rhythmic midtemporal discharge in a child without seizures.
AB  - Rhythmic midtemporal discharge (RMTD) is one of the benign epileptiform variants,
      typically consisting of runs of 4-Hz to 7-Hz activity, lasting up to 10 seconds
      and maximal over the midtemporal area. We report a child who, during an admission
      for diagnostic closed-circuit television (CCTV) and electroencephalographic (EEG)
      monitoring, was found to have prolonged rhythmic monomorphic discharges,
      alternating over both midtemporal areas, with one of the discharges lasting up to
      82 minutes. An analysis of the dominant frequency, during the longest discharge,
      showed that it was monomorphic throughout. On the basis of various features of
      these discharges, we concluded that they represented RMTD of unusual duration. 

PMID- 24864323
TI  - Intrastromal corneal ring segments implantation in patients with keratoconus: 10
      year follow-up.
AB  - PURPOSE: To evaluate the long-term safety and efficacy of Ferrara intrastromal
      corneal ring segments (ICRS) (Ferrara Ring; AJL, Boecillo, Spain) in patients
      with keratoconus. METHODS: The chart records of 36 eyes of 30 patients with
      keratoconus implanted with ICRS, operated on between July 1996 and January 2002,
      were retrospectively reviewed. The following parameters were studied: uncorrected
      distance visual acuity (UDVA), corrected distance visual acuity (CDVA),
      keratometry (K), and central corneal thickness. The outcomes were evaluated at 5
      and 10 years after ICRS implantation. RESULTS: The mean UDVA (logMAR) improved
      from 1.01 +/- 0.28 (20/200 Snellen) to 0.71 +/- 0.38 (20/100 Snellen) at 5 years
      (P < .05) and 0.67 +/- 0.25 (20/90 Snellen) at 10 years (P = .735). The mean CDVA
      (logMAR) improved from 0.45 +/- 0.45 (20/55 Snellen) to 0.24 +/- 0.19 (20/35
      Snellen) at 5 years (P < .05) and 0.29 +/- 0.09 (20/38 Snellen) at 10 years (P =
      .292). The mean maximum K value decreased from 54.99 +/- 6.33 to 50.58 +/- 5.11 D
      at 5 years (P < .05) and 50.65 +/- 5.17 D at 10 years (P = .854). The mean
      minimum K value decreased from 48.85 +/- 5.70 to 46.90 +/- 5.08 D at 5 years (P <
      .05) and 47.12 +/- 4.22 D at 10 years (P = .945). The central corneal thickness
      decreased from 457.42 +/- 58.21 to 421.34 +/- 74.12 MUm at 5 years (P = .039) and
      434.32 +/- 77.65 MUm at 10 years (P = .427). CONCLUSIONS: Intrastromal corneal
      ring segments can effectively improve UDVA and CDVA 10 years after implantation
      in patients with keratoconus.

PMID- 24864324
TI  - Creation of the Argentina-Alzheimer's Disease Neuroimaging Initiative.
AB  - The Alzheimer's Disease Neuroimaging Initiative (ADNI) is a multisite,
      longitudinal study that assesses clinical, imaging, genetic, and biospecimen
      biomarkers through the process of normal aging to mild cognitive impairment and
      dementia. We present the creation of the Argentina-ADNI - the first South
      American ADNI - and its effort to acquire data comparable with those gathered in
      other worldwide ADNI centers.

PMID- 24864325
TI  - Femtosecond laser versus manual clear corneal incision in cataract surgery.
AB  - PURPOSE: To compare functional and morphological outcomes of femtosecond laser
      clear corneal incision (CCI) versus manual CCI during cataract surgery. METHODS:
      Sixty eyes of 60 patients who underwent CCI during cataract surgery were
      randomized into two groups: femtosecond laser CCI (30 eyes) and manual CCI (30
      eyes). RESULTS: There were no significant between-group differences in
      uncorrected distance visual acuity, corrected distance visual acuity, surgically
      induced astigmatism, and corneal aberrations. Keratometric astigmatism was
      significantly lower in the femtosecond laser CCI group compared to the manual CCI
      group at 30 and 180 days (P < .05). Central endothelial cell count was
      significantly higher in the femtosecond laser CCI group compared to the manual
      CCI group at 7 and 30 days postoperatively (P < .05). A lower increase of corneal
      thickness at the incision site was observed at 30 and 180 days postoperatively in
      the femtosecond laser CCI group compared to the manual CCI group (P < .05). In
      addition, femtosecond laser CCI showed a better morphology (lower percentage of
      endothelial and epithelial gaping and endothelial misalignment) compared to
      manual CCI at different time points. Total phacoemulsification time was
      significantly lower in the femtosecond laser CCI group (P < .05). CONCLUSIONS:
      The femtosecond laser procedure was safe, efficient, and less damaging, as
      evidenced by lower central endothelial cell loss, lower increase of corneal
      thickness at the incision site, and better tunnel morphology compared to the
      manual technique.

PMID- 24864326
TI  - Comparative outcomes of bimanual MICS and 2.2-mm coaxial phacoemulsification
      assisted by femtosecond technology.
AB  - PURPOSE: To compare the efficacy and safety outcomes of bimanual microincision
      cataract surgery (MICS) versus 2.2-mm coaxial phacoemulsification assisted by
      Femtosecond LenSx (Alcon-LenSx Inc., Aliso Viejo, CA). METHODS: This prospective,
      randomized, observational, comparative case series comprised 50 cataractous eyes
      of 50 patients receiving femtosecond laser refractive lens surgery followed by a
      bimanual MICS technique with two 1-mm incisions (25 patients) (FemtoMICS group)
      and a coaxial phacoemulsification technique with a 1-mm paracentesis and a 2.2-mm
      principal incision (25 patients) (FemtoCoaxial group). The main outcomes measures
      were: ultrasound power, effective phacoemulsification time, postoperative
      spherical equivalent, higher-order aberrations (corneal and internal), corneal
      thickness, endothelial cell count, macular thickness, and complications during
      and after surgery. Both groups were absolutely comparable for all variables
      preoperatively. RESULTS: Mean ultrasound power was 1.8% +/- 0.9% for MICS and
      14.7% +/- 4.9% for 2.2-mm incisions (P < .001). Effective phacoemulsification
      time values for MICS and 2.2-mm incisions were 1.5 +/- 0.9 and 4.5 +/- 2.9 sec,
      respectively (P = .002). Mean postoperative spherical equivalent was -0.26 for
      FemtoMICS and -0.33 for FemtoCoaxial (P > .05). The efficacy index at 1 month
      postoperatively was 160.2% for FemtoMICS and 149% for FemtoCoaxial. No
      significant differences were found in corneal thickness, endothelial cell count,
      and macular thickness. Complications included posterior capsule rupture (4%) and
      anterior capsule rupture with no posterior capsule tear (4%) for FemtoMICS and
      bridges due to incomplete capsulorhexis (4%) for FemtoCoaxial. CONCLUSIONS: MICS
      and coaxial phacoemulsification techniques assisted by the Femtosecond LenSx
      achieved excellent safety and efficient outcomes. The FemtoMICS technique was
      surgically and statistically more efficient than the FemtoCoaxial technique.

PMID- 24864327
TI  - Silicone-diffractive versus acrylic-refractive supplementary iols: visual
      performance and manual handling.
AB  - PURPOSE: To compare visual outcome and manual handling of additional multifocal
      sulcus-fixated intraocular lenses (IOLs) of different materials and lens
      concepts. METHODS: Visual outcomes after implantation of a monofocal IOL in the
      capsular bag followed by implantation of a sulcus-fixated multifocal IOL (MIOL)
      in patients with cataract were assessed. Patients were randomly assigned to
      receive either the refractive Sulcoflex 653F (Rayner Surgical GmbH, Bamberg,
      Germany) (35 eyes) or the diffractive MS 714 PB Diff (Dr. Schmidt
      Intraocularlinsen GmbH, St. Augustin, Germany) (33 eyes) additional MIOL. Three
      months postoperatively, visual acuity at far, intermediate, and near distance and
      contrast sensitivity under different conditions were evaluated. Patients with
      binocular implantation were asked to rate their subjective quality of vision.
      RESULTS: No complications occurred during or after surgery. No significant
      differences in uncorrected and corrected distance visual acuity at all distances
      were found between groups. All eyes achieved uncorrected visual acuity of 0.3
      logMAR (20/40 Snellen) or better at all distances. Contrast sensitivity was
      significantly better in the diffractive MS 714 PB Diff group than in the
      refractive Sulcoflex 653F group under all conditions. The refractive Sulcoflex
      653F group experienced more photic phenomena (81%) than the diffractive MS 714 PB
      Diff group (25%), but the disturbances were scored as mild to moderate in most
      cases (93%/100%). The unfolding procedure of the acrylic Sulcoflex 653F IOL was
      smoother and more controllable than that of the silicone MS 714 PB Diff IOL.
      CONCLUSIONS: Both additional MIOLs performed well in terms of far, intermediate,
      and near vision and enabled patients to handle almost all areas of activity
      without glasses.

PMID- 24864328
TI  - Agreement between placido topography and Scheimpflug tomography for corneal
      astigmatism assessment.
AB  - PURPOSE: To evaluate inter-device agreement between Placido topography (iTrace;
      Tracey Technologies, Houston, TX) and Scheimpflug tomography (Pentacam; Oculus
      Optikgerate GmbH, Wetzlar, Germany) for measuring corneal power and cylinder and
      axis of astigmatism. METHODS: Observational case series of 54 eyes from 54
      subjects with no ocular disease. Main outcome measures were corneal power,
      cylinder power, and axis of astigmatism and their agreement was assessed by Bland
      Altman analysis. RESULTS: For corneal power and corneal cylinder, 95% limits of
      agreement (LoA) were considered good (-0.38 to 0.45 diopters [D] and -0.49 to
      0.27 D, respectively). In contrast, the 95% LoA for corneal astigmatism axis
      exceeded the clinically relevant margins (-14.8 to 13.5): 28 eyes (52%) had a
      greater than 5 degrees  difference, 10 eyes (19%) had a greater than 10 degrees 
      difference, and 4 eyes (7%) had a greater than 20 degrees  difference between
      instruments. This absolute difference was significantly correlated with average
      corneal cylinder (Spearman's r = -0.379, P = .005) but not with average corneal
      power. In eyes with corneal astigmatism 2 D or greater, the 95% LoA for axis were
      -8.7 degrees  to 6.7 degrees , whereas in those with corneal astigmatism less
      than 1 D, the 95% LoA for axis were -19.1 degrees  to 16.6 degrees . CONCLUSIONS:
      Placido topography and Scheimpflug tomography show good agreement for corneal
      power and cylinder, but not for corneal astigmatism axis. These instruments could
      be used interchangeably only in eyes with corneal astigmatism of 2 D or greater.

PMID- 24864329
TI  - Optimizing precision in toric lens selection by combining keratometry techniques.
AB  - PURPOSE: To increase precision in toric intraocular lens selection by reducing
      the frequency of outliers that arise from technology-dependent variability during
      the preoperative assessment for routine cataract surgery. METHODS: Mean
      preoperative values for absolute sphere, amount of astigmatism, and steepest
      cylindrical axis were obtained for 87 eyes (54 patients) each with a manual
      keratometer and four automated keratometers. The mean sphere, amount of
      astigmatism, and steepest cylindrical axis across five technologies for each eye
      were defined as the meld sphere, meld astigmatism, and meld axis, respectively.
      Each technology was evaluated against the meld by Bland-Altman analysis,
      Student's paired t test, and correlation coefficients. Further comparison between
      individual technologies and the meld quantified the number of outlier
      measurements each technology produced. RESULTS: The number of outliers between
      individual keratometers and the meld differed with specific measurement of
      sphere, axis, or amount of astigmatism. Although statistical analysis using Bland
      Altman plots, correlation coefficients, and paired t tests suggested
      insignificant difference from meld measurements for each parameter, precision
      guided analysis presented more clinically significant outliers. The number of
      outliers can be reduced for sphere (range: 2%-46% to 1%-6%), astigmatism (range:
      6%-23% to 0%-2%), and axis outliers (range: 15%-27% to 3%-6%) by averaging
      measurements from automated and manual keratometers. CONCLUSIONS: Although
      multiple keratometry technologies produced similar, average measurements, the
      authors found a disturbing number of outliers that may be overlooked when
      employing a single technology. Measurement errors can be dramatically reduced by
      averaging measurements from manual keratometry with any automated technology to
      make toric lens selection more precise.

PMID- 24864330
TI  - Reply: To PMID 23906785.

PMID- 24864331
TI  - Reply.

PMID- 24864333
TI  - Proceedings of the 9th International Congress of Veterinary Virology of the
      European Society for Veterinary Virology, September 4-7, 2012, Madrid, Spain.

PMID- 24864332
TI  - Special issue in honor of Karl Jaspers.

PMID- 24864334
TI  - Special issue dedicated to Sir David Alan Hopwood.

PMID- 24864335
TI  - Festschrift celebrating the career of Ming T. Tsuang.

PMID- 24864336
TI  - [Biological fight against cutaneous leishmaniasis].

PMID- 24864337
TI  - [Snake poisoning].

PMID- 24864338
TI  - [Net regression of lepra].

PMID- 24864339
TI  - [Breast cancer screening].

PMID- 24864340
TI  - [Post-conflict management of sexual violence].

PMID- 24864341
TI  - [Analysis of a center for free HIV screening].

PMID- 24864342
TI  - Maternal and neonatal tetanus elimination: validation survey in 4 States in
      India, April 2013.

PMID- 24864343
TI  - Dracunculiasis eradication--global surveillance summary, 2013.

PMID- 24864344
TI  - Monthly report on dracunculiasis cases, January -- April 2014.

PMID- 24864345
TI  - Outbreak news. Ebola virus disease, West Africa.

PMID- 24864346
TI  - Meningococcal disease control in countries of the African meningitis belt, 2013.

PMID- 24864347
TI  - Oral cholera vaccine campaign among internally displaced persons in South Sudan.

PMID- 24864348
TI  - Meeting of the Strategic Advisory Group of Experts on immunization, April 2014 --
      conclusions and recommendations.

PMID- 24864349
TI  - Special issue on photosynthesis in honor of Govindjee.

PMID- 24864356
TI  - Raves for the emergency response to marathon bombings: Special report highlights
      prescient preparation.

PMID- 24864355
TI  - Response to Jeff S. Healey, MD, MSc and Michela Brambatti, MD.

PMID- 24864357
TI  - Obama signs act to make more federally funded research open access: NIH
      requirement extended to other agencies.

PMID- 24864358
TI  - Author's response.

PMID- 24864359
TI  - [In memory of Joan Cordoba].

PMID- 24864361
TI  - [Arthritis. The cost to society].

PMID- 24864360
TI  - [Pregnancy again? The importance of folic acid].

PMID- 24864362
TI  - [Smoking outdoors. Is it necessary to protect those who are outside?].

PMID- 24864364
TI  - Outside influences on medical practice.

PMID- 24864363
TI  - [What happens after the ICU stay?].

PMID- 24864365
TI  - Copayments for medication in 2014. Final rule.
AB  - This document adopts as a final rule, without change, an interim final rule
      amending the Department of Veterans Affairs (VA) medical regulations to freeze
      the copayments required for certain medications provided by VA until December 31,
      2014. Under that rule, the copayment amounts for all veterans were maintained at
      the same rates as they were in 2013, which were $8 for veterans in priority
      groups 2-6 and $9 for veterans in priority groups 7 and 8. On January 1, 2015,
      the copayment amounts may increase based on the prescription drug component of
      the Medical Consumer Price Index (CPI-P).

PMID- 24864366
TI  - Patient Protection and Affordable Care Act; exchange and insurance market
      standards for 2015 and beyond. Final rule.
AB  - This final rule addresses various requirements applicable to health insurance
      issuers, Affordable Insurance Exchanges (''Exchanges''), Navigators, non
      Navigator assistance personnel, and other entities under the Patient Protection
      and Affordable Care Act and the Health Care and Education Reconciliation Act of
      2010 (collectively referred to as the Affordable Care Act). Specifically, the
      rule establishes standards related to product discontinuation and renewal,
      quality reporting, non-discrimination standards, minimum certification standards
      and responsibilities of qualified health plan (QHP) issuers, the Small Business
      Health Options Program, and enforcement remedies in Federally-facilitated
      Exchanges. It also finalizes: A modification of HHS's allocation of reinsurance
      collections if those collections do not meet our projections; certain changes to
      allowable administrative expenses in the risk corridors calculation;
      modifications to the way we calculate the annual limit on cost sharing so that we
      round this parameter down to the nearest $50 increment; an approach to index the
      required contribution used to determine eligibility for an exemption from the
      shared responsibility payment under section 5000A of the Internal Revenue Code;
      grounds for imposing civil money penalties on persons who provide false or
      fraudulent information to the Exchange and on persons who improperly use or
      disclose information; updated standards for the consumer assistance programs;
      standards related to the opt-out provisions for self-funded, non-Federal
      governmental plans and related to the individual market provisions under the
      Health Insurance Portability and Accountability Act of 1996 including excepted
      benefits; standards regarding how enrollees may request access to non-formulary
      drugs under exigent circumstances; amendments to Exchange appeals standards and
      coverage enrollment and termination standards; and time-limited adjustments to
      the standards relating to the medical loss ratio (MLR) program. The majority of
      the provisions in this rule are being finalized as proposed.

PMID- 24864367
TI  - Findings of research misconduct.

PMID- 24864370
TI  - Findings of research misconduct.

PMID- 24864372
TI  - [Andras Jeney -- 80 years].

PMID- 24864373
TI  - [International experts' meeting on "Operative art for translational research: the
      educational front" Debrecen, February 14-15, 2014].

PMID- 24864374
TI  - An information theoretic approach to assessing Gene-Ontology-driven similarity
      and its application.
AB  - Using information-theoretic approaches, this paper presents a cross-platform
      system to support the integration of Gene Ontology (GO)-driven similarity
      knowledge into functional genomics. Three GO-driven similarity measures
      (Resnik's, Lin's and Jiang's metrics) have been implemented to measure between
      term similarity within each of the GO hierarchies. Two approaches (simple and
      highest average similarity) which are based on the aggregation of between-term
      similarities, are used to estimate the similarity between gene products. The
      system has been successfully applied to a number of applications including
      assessing gene expression correlation patterns and the relationships between GO
      driven similarity and other functional properties.

PMID- 24864376
TI  - Estrogen receptor status prediction by gene component regression: a comparative
      study.
AB  - The aim of the study is to evaluate gene component analysis for microarray
      studies. Three dimensional reduction strategies, Principle Component Regression
      (PCR), Partial Least Square (PLS) and Reduced Rank Regression (RRR) were applied
      to publicly available breast cancer microarray dataset and the derived gene
      components were used for tumor classification by Logistic Regression (LR) and
      Linear Discriminative Analysis (LDA). The impact of gene selection/filtration was
      evaluated as well. We demonstrated that gene component classifiers could reduce
      the high-dimensionality of gene expression data and the collinearity problem
      inherited in most modern microarray experiments. In our study gene component
      analysis could discriminate Estrogen Receptor (ER) positive breast cancers from
      negative cancers and the proposed classifiers were successfully reproduced and
      projected into independent microarray dataset with high predictive accuracy.

PMID- 24864375
TI  - Seed-weighted random walk ranking for cancer biomarker prioritisation: a case
      study in leukaemia.
AB  - A central focus of clinical proteomics for cancer is to identify protein
      biomarkers with diagnostic and therapeutic application potential. Network-based
      analyses have been used in computational disease-related gene prioritisation for
      several years. The Random Walk Ranking (RWR) algorithm has been successfully
      applied to prioritising disease-related gene candidates by exploiting global
      network topology in a Protein-Protein Interaction (PPI) network. Increasing the
      specificity and sensitivity ofbiomarkers may require consideration of similar or
      closely-related disease phenotypes and molecular pathological mechanisms shared
      across different disease phenotypes. In this paper, we propose a method called
      Seed-Weighted Random Walk Ranking (SW-RWR) for prioritizing cancer biomarker
      candidates. This method uses the information of cancer phenotype association to
      assign to each gene a disease-specific, weighted value to guide the RWR algorithm
      in a global human PPI network. In a case study of prioritizing leukaemia
      biomarkers, SW-RWR outperformed a typical local network-based analysis in
      coverage and also showed better accuracy and sensitivity than the original RWR
      method (global network-based analysis). Our results suggest that the tight
      correlation among different cancer phenotypes could play an important role in
      cancer biomarker discovery.

PMID- 24864377
TI  - Multi-level clustering support vector machine trees for improved protein local
      structure prediction.
AB  - Local protein structure prediction is one of important tasks for bioinformatics
      research. In order to further enhance the performance of local protein structure
      prediction, we propose the Multi-level Clustering Support Vector Machine Trees
      (MLSVMTs). Building on the multi-cluster tree structure, the MLSVMTs model uses
      multiple SVMs, each of which is customized to learn the unique sequence-to
      structure relationship for one cluster. Both the combined 5 x 2 CV F test and the
      independent test show that the local structure prediction accuracy of MLSVMTs is
      significantly better than that of one-level K-means clustering, Multi-level
      clustering and Clustering Support Vector Machines.

PMID- 24864378
TI  - A supervised learning approach to the ensemble clustering of genes.
AB  - High-throughput techniques have become a primary approach to gathering biological
      data. These data can be used to explore relationships between genes and guide
      development of drugs and other research. However, the deluge of data contains an
      overwhelming amount of unknown information about the organism under study.
      Therefore, clustering is a common first step in the exploratory analysis of high
      throughput biological data. We present a supervised learning approach to
      clustering that utilises known gene-gene interaction data to improve results for
      already commonly used clustering techniques. The approach creates an ensemble
      similarity measure that can be used as input to any clustering technique and
      provides results with increased biological significance while not altering the
      clustering method.

PMID- 24864379
TI  - Preface. Health care provision and patient mobility. Health integration in the
      European Union.

PMID- 24864380
TI  - Patient choice, mobility and competition among health care providers.
AB  - Policymakers are increasingly designing policies that encourage patient choice
      and therefore mobility across providers. Since prices are regulated (fixed) in
      most countries, providers need to compete on quality to attract patients. This
      chapter reviews the current theoretical and empirical literature on patient
      choice and quality competition in health markets. The theoretical literature
      identifies key factors affecting incentives to provide quality. These include:
      altruistic motives, cost structure, number of providers, demand responsiveness,
      GP gatekeeping, degree of specialization, profit constraints and soft budgets. We
      also review the theoretical literature on choice across different countries (e.g.
      within the EU) or regions within the same countries. The chapter reviews selected
      empirical studies that investigate whether demand responds to quality and waiting
      times, the role of patient's mobility and the effect of competition on quality.

PMID- 24864381
TI  - Using discrete choice experiments to understand preferences in health care.
AB  - Whenever processes are reconfigured or new products are designed the needs and
      preferences of patients and consumers have to be considered. Although at times
      neglected, this becomes more and more relevant in health care settings: Which
      modes of health care delivery will be accepted? What are the patients' priorities
      and what is the willingness to pay? To which degree are patients mobile and for
      which kind of services are they willing to travel? Preferences, however, are
      difficult to measure, as they are latent constructs. This becomes even more
      difficult, when no past choices can be analyzed either as the service or the
      product is yet to be developed or as in the past there has not been free choice
      for patients. In such cases, preferences cannot be surveyed directly. Asking
      individuals openly for their attitudes towards certain services and products, the
      results are likely biased as individuals are not confronted with budget
      constraints and trade-offs. For this reason, discrete choice experiments (DCEs)
      are frequently used to elicit patient preferences. This approach confronts
      patients with hypothetical scenarios of which only one can be chosen. Over the
      past few years, this tool to reveal patients' preferences for health care has
      become very popular in health economics. This contribution aims at introducing
      the principles of DCEs, highlighting the underlying theory and giving practical
      guidance for conducting a discrete choice experiment in health economics. Thereby
      we focus on three major fields of patient demand: designing health insurance,
      assessing patient utility of new pharmaceuticals and analyzing provider choice.
      By having a closer look at selected international studies, we discuss the
      application of this technique for the analysis of the supply and the demand of
      health care as well as the implications for assessing patient mobility across
      different health care systems.

PMID- 24864382
TI  - Implications of the EU patients' rights directive in cross-border healthcare on
      the German sickness fund system.
AB  - We examine the implications of the EU directive on the application of patients'
      rights in cross-border healthcare on the German sickness fund system. Since
      Germany implemented most requirements of the directive already in 2004, we first
      review Germany's experience with EU cross-border healthcare. We then focus on the
      possible effects of increased EU cross-border healthcare. While this gives
      patients more choice, the German sickness fund system faces a number of
      challenges. EU cross-border care may undermine efforts to keep healthcare
      expenditure under control. Cross-border care can also increase inequality of
      access. Furthermore, promoting cross-border care can be a means for sickness
      funds to attract good risks. We discuss these challenges and point out possible
      policy responses.

PMID- 24864383
TI  - The possible effects of health professional mobility on access to care for
      patients.
AB  - The chapter explains how health professional mobility impacts on the resources
      and capacity available within a health system, and how this affects service
      delivery and access. The contrasting experiences of destination countries, which
      receive foreign inflows of health professionals, and of source countries, which
      loose workforce due to outflows, are illustrated with country examples. The
      evidence opens the debate on how EU countries compete for health workforce, what
      this means for resource-strained, crisis-hit Member States, and whether there is
      any room for intra-European solidarity. The nexus between patient mobility and
      health professional mobility is moreover highlighted. This take on free mobility
      in the EU has received little attention, and while evidence is scarce, it calls
      for careful analysis when considering the possible effects of free movement on
      access to care in national health systems. The chapter reformulates the question
      on 'who wins' and 'who looses' from freedom of movement in the EU to turn our
      attention away from those who go abroad for care and instead focus on those who
      stay at home.

PMID- 24864384
TI  - Patient choice and mobility in the UK health system: internal and external
      markets.
AB  - The National Health Service (NHS) has been the body of the health care system in
      the United Kingdom (UK) for over 60 years and has sought to provide the
      population with a high quality service free of user charges for most services.
      The information age has seen the NHS rapidly transformed from a socialist,
      centrally planned and publicly provided system to a more market based system
      orientated towards patients as consumers. The forces of globalization have
      provided patients in the UK with greater choice in their health care provision,
      with NHS treatment now offered from any public or approved private provider and
      the possibility of treatment anywhere in the European Economic Area (EEA) or
      possibly further. The financial crisis, a large government deficit and austerity
      public spending policies have imposed a tight budget constraint on the NHS at a
      time of increasing demand for health care and population pressure. Hence, further
      rationing of care could imply that patients are incentivised to seek private
      treatment outside the constraints of the NHS, where the possibility of much
      greater choice exists in an increasingly globally competitive health care market.
      This chapter examines the evidence on the response of patients to the
      possibilities of increased choice and mobility within the internal NHS and
      external overseas health care markets. It also considers the relationships
      between patient mobility, health care provision and health policy. Patients are
      more mobile and willing to travel further to obtain better care outcomes and
      value for money, but are exposed to greater risk.

PMID- 24864385
TI  - What drives patient mobility across Italian regions? Evidence from hospital
      discharge data.
AB  - This chapter examines patient mobility across Italian regions using data on
      hospital discharges that occurred in 2008. The econometric analysis is based on
      Origin-Destination (OD) flow data. Since patient mobility is a crucial phenomenon
      in contexts of hospital competition based on quality and driven by patient
      choice, as is the case in Italy, it is crucial to understand its determinants.
      What makes the Italian case more interesting is the decentralization of the
      National Health Service that yields large regional variation in patient flows in
      favor of Centre-Northern regions, which typically are 'net exporters' of hospital
      treatments. We present results from gravity models estimated using count data
      estimators, for total and specific types of flows (ordinary admissions, surgical
      DRGs and medical DRGs). We model cross-section dependence by specifically
      including features other than geographical distance for OD pairs, such as past
      migration flows and the share of surgical DRGs. Most of the explanatory variables
      exhibit the expected effect, with distance and GDP per capita at origin showing a
      negative impact on patient outflows. Past migrations and indicators of
      performance at destination are effective determinants of patient mobility.
      Moreover, we find evidence of regional externalities due to spatial proximity
      effects at both origin and destination.

PMID- 24864386
TI  - The impact of federalism on the healthcare system in terms of efficiency, equity,
      and cost containment: the case of Switzerland.
AB  - According to the economic theory of federalism (Oates 1999), a decentralized
      decision to collectively fund and supply the quantity and quality of public
      services will increase economic welfare as long as three conditions are
      fulfilled: preferences and production costs of the different local constituencies
      are heterogeneous; local governments are better informed than the central agency
      because of their proximity to the citizens; and the competition between local
      governments exerts a significant impact on the performance of the local
      administration and on the ability of public agencies to implement policy
      innovation. Federalism also presents some negative aspects, including the
      opportunity costs of decentralization, which materialize in terms of unexploited
      economies of scale; the emergence of spillover effects among jurisdictions; and
      the risk of cost-shifting exercises from one layer of the government to the
      other. Finally, competition between fiscal regimes can affect the level of
      equity. The literature considers fiscal federalism as a mechanism for controlling
      the size of the public sector and for constraining the development of
      redistributive measures. The present paper reviews the impact that federalism has
      on the efficiency, equity, and cost containment of the healthcare system in
      Switzerland, a country with a strongly decentralized political system that is
      based on federalism and the institutions of direct democracy, a liberal economic
      culture, and a well-developed tradition of mutualism and social security
      (generous social expenditure and welfare system). By analyzing the empirical
      evidence available for Switzerland, we expect to draw some general policy lessons
      that might also be useful for other countries.

PMID- 24864387
TI  - Patients' mobility across borders: a welfare analysis.
AB  - Welfare systems are designed on geographical and membership boundaries. In terms
      of access to health care this implies that, as a general rule, only individuals
      residing in their national territory can obtain health care from providers
      located there. However, in the past few years medical tourism has grown at an
      explosive pace throughout the world and in Europe. Each year in fact a small, but
      significant number of European citizens seek medical treatment that is financed
      by their public insurer in another EU country. From an economic point of view, it
      is important to distinguish between the two following sources of patients'
      mobility: a regulated mobility, where the third payer decides to send patients
      abroad and patients' choice, where the patient himself decides to seek care
      abroad. In this article we show how the combined effect of restrictions to the
      use of health care, transfer prices, and mobility rules determine social welfare
      and its allocation between Regions. The results are quite interesting: if the
      price set for these patients is equal to the marginal cost of the more efficient
      Region, patients' mobility should be preferred to patients' choice. On the other
      hand, if the price is equal to the marginal cost of the less efficient Region,
      patient choice should be preferred. The other interesting result is a possible
      trade off between a static model where each Region chooses its level of
      cost/effectiveness and a more long-term situation, where patient mobility
      determines a common level for this parameter.

PMID- 24864388
TI  - Quality competition and uncertainty in a horizontally differentiated hospital
      market.
AB  - The chapter studies hospital competition in a spatially differentiated market in
      which patient demand reflects the quality/distance mix that maximizes their
      utility. Treatment is free at the point of use and patients freely choose the
      provider which best fits their expectations. Hospitals might have asymmetric
      objectives and costs, however they are reimbursed using a uniform prospective
      payment. The chapter provides different equilibrium outcomes, under perfect and
      asymmetric information. The results show that asymmetric costs, in the case where
      hospitals are profit maximizers, allow for a social welfare and quality
      improvement. On the other hand, the presence of a publicly managed hospital which
      pursues the objective of quality maximization is able to ensure a higher level of
      quality, patient surplus and welfare. However, the extent of this outcome might
      be considerably reduced when high levels of public hospital inefficiency are
      detectable. Finally, the negative consequences caused by the presence of
      asymmetric information are highlighted in the different scenarios of
      ownership/objectives and costs. The setting adopted in the model aims at
      describing the up-coming European market for secondary health care, focusing on
      hospital behavior and it is intended to help the policy-maker in understanding
      real world dynamics.

PMID- 24864389
TI  - Cross border health care provision: who gains, who loses.
AB  - The diffusion of the welfare state has produced a widespread involvement of the
      public sector in financing the production of private goods for paternalistic
      reasons. In this chapter we model the production of health care as a merit impure
      local public good whose consumption is subsidized and whose access is free, but
      not unlimited. The impure local public good aspect means that the production of
      health care spreads its benefits beyond the geographical boundaries of the Region
      where it is produced. Finally, we include the (optional) provision of an
      equalization grant that allows reduction of fiscal imbalance among Regions. In
      this framework we study the possible effects of cross border provision of health
      care. We assume that information is complete and symmetric and that there is no
      comparative advantage in local provision. In this context devolution is always
      suboptimal for the whole community: the lack of coordination means that the
      impure public good is under-provided. However, more efficient Regions may be
      better off because of the impure public good nature of health care.

PMID- 24864391
TI  - Why does Alpha Omega care so much about Israel?

PMID- 24864390
TI  - Visions and dreams for our future: given on honor's night at the 2012
      International Convention.

PMID- 24864392
TI  - If only I knew...!

PMID- 24864393
TI  - Myofascial trigger point pain.
AB  - Myofascial trigger point pain is an extremely prevalent cause of persistent pain
      disorders in all parts of the body, not just the head, neck, and face. Features
      include deep aching pain in any structure, referred from focally tender points in
      taut bands of skeletal muscle (the trigger points). Diagnosis depends on accurate
      palpation with 2-4 kg/cm2 of pressure for 10 to 20 seconds over the suspected
      trigger point to allow the referred pain pattern to develop. In the head and neck
      region, cervical muscle trigger points (key trigger points) often incite and
      perpetuate trigger points (satellite trigger points) and referred pain from
      masticatory muscles. Management requires identification and control of as many
      perpetuating factors as possible (posture, body mechanics, psychological stress
      or depression, poor sleep or nutrition). Trigger point therapies such as spray
      and stretch or trigger point injections are best used as adjunctive therapy.

PMID- 24864394
TI  - Sleep bruxism: review and update for the restorative dentist.
AB  - Sleep bruxism (SB) is a parafunctional oromotor activity that can sometimes pose
      a threat to the integrity of the structures of the masticatory system if the
      magnitude and direction of the forces exerted exceed the system's adaptive
      capacity. Over the years science has tried to provide a consistent explanation of
      the etiopathogenesis and physiopathology of SB, although the pathophysiological
      mechanisms are, even now, not fully understood yet. There is at present no
      specific, effective treatment to permanently eliminate the habit of SB. There are
      only palliative therapeutic alternatives steered at preventing the pathological
      effects of SB on the stomatognathic system and alleviating the negative clinical
      consequences of the habit. The aim of this paper is to review and update the
      fundamental scientific concepts of SB based on the scientific literature and to
      furnish an approach to the main types of therapy available, in an attempt to
      assist the general and restorative dentist to manage those clinical situations in
      which SB is a significant risk factor for the oral health and/or dental treatment
      of the patient.

PMID- 24864395
TI  - Sleep basics and sleep-pain interrelations for orofacial pain dentists.

PMID- 24864396
TI  - Epilogue: if only we knew...

PMID- 24864397
TI  - Are you removing your PVS impression materials too soon?

PMID- 24864398
TI  - One moment in time.

PMID- 24864399
TI  - A rewarding experience.

PMID- 24864400
TI  - Management of complications of dentoalveolar surgery.

PMID- 24864401
TI  - Routine and complicated extractions: avoiding and managing complications.
AB  - Dental extractions are commonly performed procedures in dentistry. For a number
      of different reasons, there can be serious complications both during surgical
      procedures and during patient recovery. Many of these complications can be
      avoided by recognizing "red flags" in advance of untoward events and by taking
      steps to prevent or manage such problems. Prior to surgery, the dentist needs
      quality radiographs, must be familiar with the patient's health conditions and
      medications, and have the knowledge and expertise to perform routine and
      "surgical" extractions safely, expeditiously, and with minimal (if any) loss of
      adjacent bone. This article, although not "all-inclusive," outlines procedures
      that help us either confirm correct methods we are already using or enhance our
      ability to become better. It reviews items that clinicians must be aware of and
      anticipate to allow exodontia to be done more smoothly and effectively.

PMID- 24864403
TI  - Antibiotics or no antibiotics: reflections on Ren and Malmstrom.
AB  - This article is intended to be a review of current studies on the effectiveness
      of antibiotics in limiting postoperative complications after third molar
      exractions; in search of conclusions above and beyond Ren and Malmstroms'
      excellent meta-analysis.

PMID- 24864402
TI  - Minimizing alveolar bone loss during and after extractions (Part I)--review of
      techniques: atraumatic extraction, root retention.

PMID- 24864404
TI  - Reduced complications by modified and grafted coronectomy vs. standard
      coronectomy--a case series.
AB  - PURPOSE: The best researched method to decrease nerve injury during the removal
      of lower third molars is Intentional Partial Odontectomy or Standard coronectomy
      (SC). Despite an excellent track record, complications still exist. The purpose
      of this article is to introduce a case series of modified and grafted coronectomy
      (MGC), designed to minimize the drawbacks of SC. MATERIALS AND METHODS: Sixteen
      patients, with total of 20 teeth, were followed for 6 to 49 months. Amendments to
      SC were intra-surgical stabilization of the root and the creation of a
      periodontal "scaffold." RESULTS: MGC showed excellent alveolar bone height and
      periodontal improvement, with remarkable bone regeneration. No residual root
      migration was evident on follow up, nor was there inadvertent intraoperative root
      removal. CONCLUSION: This technique may be considered a good alternative to a SC,
      especially in cases of high risk for, or existent periodontal defects on the
      distal of second molars or if no residual root migration is desired.

PMID- 24864405
TI  - Lingual and inferior alveolar nerve injuries after third molar removal.
AB  - Trigeminal nerve injury is a rare, but serious complication of a common
      procedure, which results in a clinically relevant problem that deserves
      attention. The emergence of microsurgical repair of trigeminal injury has
      provided clinicians with treatment options for patients who experience persistent
      neurosensory deficits. The area of microsurgical repair of trigeminal nerves is
      now in its adolescence. While great strides have been made in the field since its
      conception, it is certain that a new generation of oral and maxillofacial
      surgeons wil bring further progress to the field. In the future, better
      quantitative sensory testing methods, more accurate imaging modalities, and
      advances in surgical technique will certainly improve the management of patients
      with impacted third molars. As clinicians, every day we are confronted with the
      management of impacted third molars. It is important to evaluate each patient
      individually with an appropriate clinical and radiographic exam. Every patient
      should be informed of the relative risks and benefits of third molar removal and
      a joint decision should be reached between the clinician and patient regarding
      ideal treatment. However, even with ideal management, complications will occur.
      If a patient does present with signs of a nerve injury the clinician should
      carefully document the neurosensory deficit and monitor the patient over time. If
      the patient exhibits a significant sensory deficit for more than one month a
      referral for evaluation to a tertiary care center capable of surgical repair of
      the injury is recommended. The occurrence of a "trigger" or Tinel's like sign is
      improtant as an indication for surgery but may not occur for a month after
      injury.

PMID- 24864407
TI  - In honor of the 60th year of Hadassah/Hebrew University School of Dental Medicine
      founded by Alpha Omega.

PMID- 24864406
TI  - 130-year-old founder tells all: Alpha Omega and the fight against prejudice.

PMID- 24864408
TI  - Tel Aviv University, School of Dental Medicine: new beginnings.

PMID- 24864409
TI  - [Latin American Association of Nursing Schools (ALADEFE). Internationalization of
      nursing knowledge].

PMID- 24864410
TI  - [Falls in people with intellectual disability: can we anticipate and prevent
      them?].
AB  - OBJECTIVE: Falls are the second leading cause of accidental or unintentional
      injury deaths worldwide, also, falls generate severe disabilities,
      institutionalization and increase healthcare costs. People with intellectual
      disabilities (ID) fall over frecuently. It's due to they are usually sicker than
      the rest of the population, and for environmental, professional and
      organizational factors. The aim of the study was to assess risk factors and
      injury due to falls. Also the methods of assessment and prevention of falls were
      analyzed. METHODOLOGY. It was carried out a literature review. We searched for
      articles in major biomedical databases and on the website of the Spanish
      Confederation of Organizations for Persons with Intellectual Disability (FEAPS).
      Sixteen studies were analyzed. The articles analyzed showed that age, history of
      seizures, gait and behavioral problems and environmental factors were the main
      risk factors for falling. Many fallers (84 6%) had suffered injuries.
      RESULTS/CONCLUSIONS: There is no consensus on an appropriate instrument to assess
      the risks factors and problems that cause falls. These instruments have not been
      validated in Spanish. A few suggestions found to prevent falls and injury in
      people with intellectual disability are based on educational and environmental
      approaches. The best way to contribute to the prevention could be research on
      intervention programs and organizational and staff characteristics. Nurses must
      lead these investigations.

PMID- 24864411
TI  - [Development and implementation of a new information process to critical
      patients' families: participatory action research].
AB  - The need for information to the families of critically ill patients is still not
      covered by the professionals involved. OBJECTIVE: Develop and implement a new
      process of informing relatives of critically ill patients. METHODOLOGY:  DESIGN:
      Participatory Action Research guided by the PEPPA Model (A Participatory,
      Evidence-Based, Patient-Focused Process for Advanced Practice Nursing Role
      Development, Implementation, and Evaluation). Field of study: general ICU of a
      tertiary university hospital (December 2011-May 2012). SAMPLING: convenience.
      SAMPLE: 11 relatives, 10 nurses and 8 doctors with more than one year of
      experience in ICU. DATA COLLECTION: semi-structured interviews and 10 participant
      observations. DATA ANALYSIS: content analysis of the interviews, observations and
      field notes. RESULTS: The EPA identified the need to systematize and structure
      the information process to families. Having received approval and commitment from
      the major stakeholders (doctors and nurses), we designed an algorithm and
      protocol performance, based on the results and on the best available evidence, to
      improve the process information to families of critically ill patients. To do
      this, EPA developed the following skills: direct clinical practice, coaching and
      guidance, consultation, collaboration, leadership, research and ethical decision
      making. CONCLUSIONS: A plan to improve the relatives of critically ill
      patients'process of information has been developed and implemented by the EPA. By
      the evaluation, it will be able to see the benefits of incorporating the advanced
      role and encourage its implementation in Spain.

PMID- 24864412
TI  - [Recommendations from CDC for the prevention of catheter-related infections (2013
      update)].
AB  - Nosocomial infections or infections related to health-care system have a great
      impact in the healthcare due to its high frequency and high morbidity and
      mortality they caused. Inside of them, there are the catheter-related
      bacteraemia. The paper of the nursing in the care and maintenance of the
      intravenous therapy is basic to avoid this type of infections. There has been
      demonstrated the efficacy of the implementation of catheter-related infections
      prevention programmes through a bundle of measures about the insertion,
      maintenance, surveillance and prevention of adverse events in the vascular
      access. The aim of this work is to show and emphasize the last updated
      recommendations collected in the 2011 Guidelines for the Prevention of
      Intravascular Catheter-Related Infections to nursing staff.

PMID- 24864413
TI  - [Health education to patients undergoing arteriovenous fistula].
AB  - OBJECTIVE: One of the functions of nursing is the Health Education. In this paper
      we analyze the response of patients with chronic renal failure undergoing
      arteriovenous fistula to propose interventions for self-care. We value the
      knowledge and training acquired and satisfaction. METHODOLOGY: We develop a
      descriptive study including some variables that could influence on the
      understanding, such as sex, age and place of residence. We included a sample of
      80 patients who were explained the nursing care to be applied to the
      arteriovenous fistula for hemodialysis in the future. They were given a booklet
      with this information reflected and we phoned them after. RESULTS/CONCLUSIONS:
      Patients expressed their usefulness and the results lead us to believe that
      written information could be instrumental in Health Education reinforcement,
      especially in older patients, although none of the studied factors show
      statistical differences.

PMID- 24864414
TI  - [Measurement of intra-abdominal pressure with intravesical system Unometer Abdo
      Pressure].
AB  - The measurement of intra-abdominal pressure (IAP) has been incorporated routinely
      in Critical Units in order to monitor and control those clinical situations that
      make us suspicious of intraabdominal hypertension (IAH). There are several
      methods to measure IAP [1-3]: direct measurement, a catheter inserted through
      suprapubic aspiration, although it is a discouraged procedure by being very
      invasive; and indirect measurement. In this method there are mainly three
      different techniques: Through femoral vein puncture: a catheter into the inferior
      vena cava is channeled. It is a technique being deprecated invasive, associated
      with venous thrombosis, retroperitoneal hematoma and infection. Through a gastric
      tube: impractical, requires managing large amounts of water associated with
      leakage through the pylorus risk. Through intravesical measurement: is the most
      commonly used method. The bladder catheter allows monitoring the PIA and diuresis
      and electrolyte control. This method has potential for infection associated with
      catheterization risk. Although this risk, it is considered the gold standard for
      the measurement of IAP. Have now been introduced to the market each measuring
      intravesical kits guaranteeing sterility circuit without disconnections. It is
      necessary to know the material and the correct procedure for measuring the PIA
      and how to interpret the results.

PMID- 24864415
TI  - [Medication adherence and use of health services in patients with psychosis in
      the region of Osona (Catalonia, Spain)].
AB  - OBJECTIVE: To describe and analyze sociodemographic and clinical characteristics,
      medication adherence and use of health resources by country of birth of psychosis
      diagnosed patients treated with long-term antipsychotic injectable drugs in the
      region of Osona (Catalonia, Spain). METHOD: Descriptive observational study in
      psychosis diagnosed patients over 18 years old, receiving long-term antipsychotic
      injectable treatment and treated at a Mental Health Center for adults in Vic
      (Catalonia, Spain). RESULTS: 185 patients were included, of them: 163 (88.1%)
      were born in Spain and 22 (17.9%) abroad. The sample was gender homogeneous with
      differences in age, employment status, family situation and diagnosis (p < 0.05).
      Findings about medication adherence to long-term antipsychotic injectable
      ambulatory treatment reflected good compliance in both populations. 57.7% of
      Spain-born patients and 9.1% of abroad-born patients received the injectable
      treatment at Primary Care Center (p < 0.001). The rest of them received the
      treatment at Mental Health Center for adults. 22 patients (711.9%) were admitted
      at psychiatry hospitalization ward, 16 (9.8%) of them were born in Spain and 6
      (27.3%) abroad (p = 0.012). CONCLUSIONS: All patients diagnosed with psychosis,
      either born or not in Spain, describe good adherence to long-term antipsychotic
      injectable treatment, with similar use of health resources from a quantitative
      point of view and some differences in the type of visits.

PMID- 24864416
TI  - [Palliative nursing care: drugs and pain].

PMID- 24864417
TI  - [Career guidance for registered nurse in the UK].
AB  - Cuts in temporary contracts has had big consequences for newly qualified nurses
      with regards to finding employment. This cut in contracts has resulted in a
      doubling in the rate of unemployment in this profession. In the past nurses
      emigrated to other countries for purposes like knowledge of the language or to
      extend their training and experience, however today the emigration has become the
      only way out for many professional nurses. The reputation of nurses in Spain is
      recognised internationally, with the UK being one of the countries with the
      largest demand for Spanish nurses. Due to the great amount of job opportunities
      that are emerging in the UK, nurses need help and guidance in their careers, and
      also nurses need training in areas such as Professional Body, developing a
      curriculum, facing an interview etc...

PMID- 24864418
TI  - [SwabCap and SwabFlush. A barrier to contamination in the blood stream].

PMID- 24864419
TI  - [The European Association for Wound Care (EWMA) visits Madrid].

PMID- 24864420
TI  - Washington state initiative trims Medicaid budget, ED utilization without denying
      access.
AB  - In its first year of operation, Washington state's "ER is for Emergencies"
      initiative has helped to save the state's Medicaid budget $33.6 million. The
      initiative, which is based on the implementation of seven best practices, has
      succeeded in part by improving care coordination and by linking EDs across the
      state so information can be shared electronically. Leaders of the effort concede
      that while state pressure was essential in pushing providers to address excess
      use of the ED for nonemergency needs, they stress that the approach worked
      because all sides were willing to sit down and hammer out a solution. Further,
      they note that the infrastructure is now in place to address other problems in a
      similar fashion. An analysis of claims data shows that in the first year of the
      initiative, ED visits by Medicaid recipients declined by 9.9%, and the rate of
      visits by frequent ED utilizers declined by 10.7%. The analysis also shows that
      ED visits resulting in a scheduled drug prescription fell by 24%, and the rate of
      visits for a low-acuity diagnosis declined by 14.2%. While many EDs had to adjust
      their staffing and other resources to accommodate reduced volumes, others
      experienced few changes or even saw an uptick in volume, possibly from
      implementation of the Affordable Care Act. Leaders of the effort say the biggest
      challenge involved with implementing the initiative was securing administrative
      buy-in for investments that would likely result in improved efficiency and care,
      but also reduced revenue--at least initially.

PMID- 24864421
TI  - Address burnout with a caring, nurturing environment.
AB  - With their hectic schedules and demanding work responsibilities, emergency
      physicians are particularly vulnerable to symptoms of burnout. One study showed
      that more than half of emergency providers reported at least one symptom of
      burnout when they were asked to fill out a survey tool used to measure burnout-
      more than any other type of provider. It's a concern because physicians
      experiencing burnout may be less attentive to their patients, and some ultimately
      choose to leave medicine because they are no longer satisfied with their work.
      However, there are steps health systems and administrators can take to help
      physicians who are struggling, and prevent isolated problems from escalating into
      larger issues. When a national sample of more than 7,200 physicians agreed to
      take the Maslach Burnout Inventory, a survey tool used to measure burnout, nearly
      half (45.8%) reported at least one symptom of burnout, and 65% of the emergency
      providers reported symptoms of burnout. Burnout is not just fatigue. It involves
      disappointment in a relationship or relationships, and lack of satisfaction or
      fulfillment with work, according to experts. Symptoms may include moodiness,
      irritability, sarcasm, and may result in performance issues as well. Further,
      there may be physical changes such as weight loss or changes in appetite. To
      prevent or address burnout, experts advise health systems to nurture a caring,
      collaborative environment, and to make sure that providers have mentors or
      resources to reach out to if they are experiencing any work-related problems.
      They also advise administrators to make sure that burnout is a safe topic of
      conversation.

PMID- 24864422
TI  - Medical record cloning: when documenting, avoid the temptation.

PMID- 24864424
TI  - Go fish or cut bait.

PMID- 24864423
TI  - New report: cultural changes, technology enhancements needed to move the needle
      further on safe medication practices.
AB  - A new analysis of data gleaned from the 2011 Medication Safety Self-Assessment
      for Hospitals shows that while hospitals have made great strides in adopting safe
      medication practices since the survey was first used in 2000, there is still
      considerable room for improvement, particularly in areas related to patient
      information, staff competency and education, and drug information. More than
      1,300 hospitals voluntarily submitted data for latest survey, which was developed
      by the Institute for Safe Medication Practices (ISMP). From these findings, the
      ISMP has established a list of national priorities for improvement efforts in the
      coming years. Medication errors are still the most common cause of patient harm
      in hospitalized patients, causing at least one death per day. The authors of the
      new report stress that ED administrators and providers should take the lead in
      adopting many of the recommended safe medication practices. Going forward, the
      ISMP recommends that hospitals adopt specific technology enhancements, make full
      use of clinical pharmacists, appoint chief medication safety officers to oversee
      improvement efforts, and move to strengthen training and competency on medication
      safety.

PMID- 24864425
TI  - Big Data becoming a mined-over matter. Are breaches heading toward outbreak
      status?

PMID- 24864426
TI  - Speaking of Union hospital ... Speech technology improves productivity and
      reduces costs for community hospital.

PMID- 24864427
TI  - Recognizing the power of speech. A discussion examining trends relative to voice
      driven documentation.

PMID- 24864428
TI  - Minders keepers. Healthcare organizations strive to engage patients in care
      delivery, population health via IT.

PMID- 24864429
TI  - What is population health management? Exploring a structured sequence to create
      new approaches to population health management.

PMID- 24864430
TI  - From just coping to making profits. A conversation on practice management.

PMID- 24864431
TI  - Giving the influencer his due. A call to create environments that empower
      patients.

PMID- 24864432
TI  - Healthcare's growing data opportunity. Leveraging clinical intelligence to
      elevate population health management strategies.

PMID- 24864433
TI  - [Basic and clinical understanding and perspective of nonarteritic anterior
      ischemic optic neuropathy].

PMID- 24864434
TI  - [Nonarteritic ischemic optic neuropathy animal model and its treatment
      applications].
AB  - Nonarteritic ischemic optic neuropathy (NAION) is one of the most common acute
      unilaterally onset optic nerve diseases. One management problem in terms of NAION
      is the difficulty of differential diagnosis between NAION and anterior optic
      neuritis (ON). A second problem is that there is no established treatment for the
      acute stage of NAION. A third problem is that there is no preventive treatment
      for a subsequent attack on the fellow eye, estimated to occur in 15 to 25% of
      patients with NAION. For differentiation of acute NAION from anterior optic
      neuritis, we investigated the usefulness of laser speckle flowgraphy (LSFG). In
      the normal control group, the tissue blood flow did not significantly differ
      between the right and left eyes. In the NAION group, all 6 patients had 29.5%
      decreased mean blur rate (MBR), which correlates to optic disc blood flow, of the
      NAION eye compared with the unaffected eye. In the anterior ON group, all 6 cases
      had 15.9% increased MBR of the anterior ON eye compared with the unaffected eye.
      Thus, LSFG showed a difference of the underlying pathophysiology between NAION
      and anterior ON despite showing disc swelling in both groups and could be useful
      for differentiating both groups. For the treatment of acute stage of NAION, we
      tried to reproduce the rodent model of NAION (rNAION) developed by Bernstein and
      colleagues. To induce rNAION, after the administration of rose bengal(RB) (2.5
      mM) into the tail vein of SD rats, the small vessels of the left optic nerve were
      photoactivated using a 514 nm argon green laser (RB-laser-induction). In the RB
      laser-induction eyes, the capillaries within the optic disc were reduced
      markedly, the optic disc became swollen, and fluorescein angiography showed
      filling defect in the choroid and the optic disc at an early stage, followed by
      hyperfluorescence at a late stage. Electrophysiological evaluation revealed that
      visual evoked potential (VEP) amplitude was significantly decreased but an
      electroretinogram (ERG) did not show a significant difference either in the b
      wave or in the oscillatory potentials. The scotopic threshold response (STR) was
      significantly reduced 3 days after induction. These findings are similar to those
      of rNAION and indicate that we succeeded in reproducing the rNAION.
      Histopathologic examination in the acute phase of rNAION, showed acellular NFL
      swelling anterior to the optic disc. No accumulation of inflammatory cells was
      noted in several microscopic sections of the optic nerve. In addition,
      immunochemical staining was negative throughout the retina and optic nerve. These
      results suggested that the rNAION-induced NFL swelling was not a result of
      inflammation. In the chronic phase of rNAION, the morphologic retinal changes
      were apparent in only the retinal ganglion cell(RGC) layer, with a reduction in
      the number of cells in the RGC layer. Thus, we need to evaluate the degree of the
      NFL swelling in the acute phase and the following thinning of the NFL in the
      chronic phase for efficacy of the treatment of rNAION. Therefore, we used optical
      coherence tomography (OCT) for the objective and quantitative evaluation of the
      retinal nerve fiber layer (RNFL) thickness around the optic disc changes in
      rNAION. The second method was to use the STR for the evaluation of the RGC
      function. The third method was to count the number of surviving RGCs observed and
      photographed through the fluorescence microscope with the Fluorogold staining. A
      possible rationale for treatment of NAION is that dilation of the posterior
      ciliary artery (PCA) increases the blood flow to the optic nerve and could
      improve the optic nerve function. To clarify the vasodilatory effects of
      medications, we used in vitro isometric tension recording methods and examined
      the vasodilatory effects of bevacizumab as an anti-vascular endothelial growth
      factor (VEGF) antibody, methylprednisolone as a corticosteroid and sodium
      nitroprusside (SNP, a nitric oxide donor) as a vasodilator on high-K (potassium)
      solution-induced contraction in isolated rabbit PCA. Bevacizumab did not relax
      rabbit PCA. Methylprednisolone relaxed rabbit PCA nitric oxide (NO)
      independently. SNP relaxed rabbit PCA by exogenous NO. On the basis of these
      results, we selected the following candidates for rNAION treatment:
      methylprednisolone as the corticosteroid and L-arginine as the NO related agent.
      Intravenous infusion of methylprednisolone significantly decreased the degree of
      acute disc edema but did not reduce inner retinal thinning, decrease STR
      amplitude, or decrease RGC numbers in rNAION. Intravenous infusion of L-arginine
      after rNAION induction significantly decreased the disc edema at the acute stage
      and the thinning of the inner retina, reduced the decrease in STR amplitude, and
      reduced the decrease in RGC numbers during rNAION. These results indicated that L
      arginine treatment is effective for reducing the anatomical changes and improving
      visual function in the acute stage of rNAION. To strengthen the neuroprotective
      effect for rNAION, we tried treatment using transcorneal electric stimulation
      (TES). We evaluated the effect using STR and survival RGCs. Decreased amplitude
      in the STR of the TES group was significantly better preserved than in the
      control group on the 28th day after treatment. RGC survival in the TES group was
      significantly larger than in the control group on the 14th and 28th days. The
      neuroprotective effect of TES was better than that of L-arginine. For preventive
      treatment of subsequent attack in the fellow eye, we investigated whether
      pretreatment with L-arginine might reduce the severity of the anatomical changes
      associated with NAION and preserve the visual function when NAION occurs in the
      other eye. In the L-arginine pretreated eyes, the disc edema at the acute stage
      and the thinning of inner retina were significantly decreased, and the decrease
      of STR amplitude and the decrease in RGC numbers during rNAION were reserved.
      These results indicate that pretreatment with L-arginine is effective for the
      reduction of the severity during recurrence in the other eye. We will perform
      clinical trials in a small series of cases, and if the treatment is effective, we
      will proceed to multicenter randomized treatment trials. In addition to that,
      more work needs to be done to discover better treatment options for NAION.

PMID- 24864435
TI  - [Comparison of outcomes of conventional laser versus pascal laser for diabetic
      retinopathy].
AB  - PURPOSE: To assess the efficacy and outcomes of PASCAL laser versus conventional
      laser for panretinal photocoagulation (PRP) in the treatment of diabetic
      retinopathy. METHODS: A retrospective chart review of 26 eyes at Nagoya City
      University Hospital which had undergone PRP with a follow-up of at least 6
      months. The study endpoints were change in visual outcome, central retinal
      thickness (CRT), laser setting parameters, and total number of PRP and
      complications. RESULTS: Ten eyes of conventional laser-treated patients and 16
      eyes of PASCAL-treated patients were reviewed. There were significant differences
      in the laser treating parameters between the PASCAL laser treatment and
      conventional laser treatment in power, duration, number of sessions and total
      spot counts including additional treatments (p < 0.01). Among the patients who
      had undergone PRP in the PASCAL group there was an average of 4195 spots, larger
      than the conventional laser group (p < 0.0001). There were no significant
      differences between PASCAL group and conventional laser group in complications
      and in ability to prevent visual loss and CRT. CONCLUSION: Our data suggested
      that PASCAL laser might need tighter spacing and more total spot counts to
      achieve an effect equal to traditional conventional laser treatment.

PMID- 24864437
TI  - [Follow-up study on patients with vernal keratoconjunctivitis undergoing topical
      0.1% tacrolimus treatment].
AB  - PURPOSE: A retrospective study for evaluating the clinical course of patients
      with vernal keratoconjunctivitis (VKC) treated with topical tacrolimus ophthalmic
      suspension 0.1% (Tacrolimus). SUBJECTS AND METHODS: Subjects were 30 patients (24
      men and 6 women) with VKC who were treated with a combined therapy of Tacrolimus
      and antiallergic ophthalmic solution, and could be followed up for six months.
      The subjects were divided into two groups: 1. A conversion treatment group in
      which Tacrolimus was substituted for a steroid ophthalmic solution [21 patients;
      average age 14.7 +/- 9.44 years (mean +/- SD)] and 2. An additional treatment
      group receiving Tacrolimus and anti-allergic ophthalmic solution [9 patients;
      average age 28.2 +/- 7.31 years (mean +/- SD)]. The therapeutic effects of the
      patients were evaluated chronologically using the ocular clinical score according
      to the papillae-limbus-cornea grading score and eosinophil cationic protein (ECP)
      levels in tears. RESULTS: Papillae-limbus-cornea grading scores were
      significantly decreased from 8 (median) points at instillation initiation to 5
      points at the first month after initiation of Tacrolimus treatment (p < 0.01,
      Steel test). Tear ECP levels were significantly decreased from 3493.6 (median)
      ng/ml at instillation initiation to 205.6 ng/ml at the first month after
      initiation of Tacrolimus treatment (p < 0.05, Steel test). During the course,
      four cases of exacerbation were found among the 30 cases, but no infections of
      the anterior segment were found. CONCLUSION: The therapeutic effect of Tacrolimus
      eye drops for vernal keratoconjunctivitis was remarkable at one month after
      instillation initiation. For evaluating the effect of treatment and diagnosing
      exacerbation in VKC treated with Tacrolimus, a follow-up examination using
      clinical indexes such as the papillae-limbus-cornea grading score and ECP levels
      in tears is beneficial.

PMID- 24864436
TI  - [Evaluation of dectin-1 and BAFF expression in conjunctival epithelial cells].
AB  - PURPOSE: To investigate the expression of dectin-1 protein in conjunctival
      epithelial cells and the expression of dectin-1 and B-cell activating factor
      belonging to the tumor necrosis factor family (BAFF) mRNA in in vivo conjunctival
      epithelial cells (CECs) and in vitro cultured CECs, and its difference in
      topographical change and etiology of disorders. SUBJECTS AND METHODS: 1.
      Investigation of dectin-1 and BAFF expression by cytodiagnosis of CECs. The
      subjects were 12 eyes of 12 healthy volunteers (control group), 6 eyes of 6
      patients with Sjogren syndrome (Sjogren group) and 10 eyes of 10 patients with
      vernal keratoconjuctivitis (VKC group). CECs were sampled by impression cytology
      using nitrocellulose membrane. The expression of dectin-1 in CECs was detected by
      immunofluorescence and the quantitative determination of dectin-1 mRNA and BAFF
      mRNA expression was performed by real-time polymerase chain reaction(real-time
      PCR). 2. Investigation of dectin-1 and BAFF expression using cultured CECs.
      Cultured CECs which were divided into an OK-432 addition group (addition
      concentrations: 0.02, 0.1, 0.5KU/mL), a lipopolysaccharide (LPS) addition group
      (addition concentrations : 80, 160, 320 microg/mL) and an additive-free group
      were cultured. Quantitative determination of dectin-1 mRNA and BAFF mRNA
      expression in cultured CECs was performed by real-time PCR. RESULTS: 1.
      Investigation of dectin-1 and BAFF expression by cytodiagnosis of CECs. In the
      control group, there was no significant topographical difference in the
      expression of dectin-1 and the amount of dectin-1 mRNA among superior, inferior
      tarsal conjunctiva and temporal bulbar conjunctiva. The levels of dectin-1 mRNA
      expression were 1.5 (0.1-4.0) [median value (range)] for the control group, 2.6
      (1.1-4.8) for the Sjogren group and 3.6 (1.7-16.6) for the VKC group. The VKC
      group showed a significantly higher level of dectin-1 mRNA than the control group
      (p < 0.01, Kruskal-Walles H-test). The levels of BAFF mRNA expression were 2.8
      (0.2-13.8) [median value (range)] for the control group, 6.3 (2.1-15.1) for the
      Sjogren group and 11.2 (3.5-70.8) for the VKC group. The VKC group showed a
      significantly higher level of dectin-1 mRNA than the control group (p < 0.01,
      Kruskal-Walles H-test). Moreover, regarding the relationship between expression
      level of dectin-1 mRNA and that of BAFF mRNA in all the subjects, there was a
      significant correlation between them (r = 0.75, p < 0.001, Spearman's rank
      coefficient). The levels of dectin-1 mRNA expression in the moderate and severe
      VKC group 9.2 (2.6-16.6) [median value (range)] were significantly higher than
      those in mild VKC group 2.8 (1.7-3.8) (p < 0.05, Mann-Whitney U-test). The levels
      of BAFF mRNA expression in the severe and moderate VKC groups 17.4 (9.1-70.8)
      [median value (range)] were significantly higher than those in the mild VKC group
      4.3 (3.5-11.2) (p < 0.05, Mann-Whitney U-test). 2. Investigation of dectin-1 and
      BAFF expression by cultured CECs. In the OK-432 addition group, the expression
      levels of dectin-1 mRNA were increased dose-dependently due to the OK-432
      stimulation (p < 0.05, Kruskal-Wallis H-test). Moreover, regarding the
      relationship between the expression level of dectin-1 mRNA and that of BAFF mRNA
      in all the cultured conjunctival epithelial cells stimulated by OK-432, there was
      a significant correlation between them (r = 0.85, p < 0.005, Spearman's rank
      coefficient). CONCLUSIONS: We concluded that dectin-1 expression in CECs was
      demonstrated, and expression of both dectin-1 and BAFF in CECs is thought to be
      involved in pathologic aggravation of allergic inflammatory in patients with VKC.

PMID- 24864438
TI  - [Direct observation of rotary catalysis of rotorless F1-ATPase with high-speed
      AFM].

PMID- 24864439
TI  - [Raman microscope imaging of molecules in living systems].

PMID- 24864440
TI  - [Application of nitrogen-vacancy centers of diamonds to biological imaging].

PMID- 24864442
TI  - [The development of single molecular method for the study on the signal
      transduction mechanism of microbial rhodopsins].

PMID- 24864441
TI  - [Protein labeling technology based on mutant enzyme and its application to new
      biological research tools].

PMID- 24864443
TI  - [Compatible use of fluorescence and chemiluminescence imaging with optogenetic
      stimulation during "dead-time" of CCD camera at real time].

PMID- 24864444
TI  - [Analysis of mechanochemical dynamics of actomyosin interactions revealed by
      single molecule optical trap microscope].

PMID- 24864445
TI  - [Cooperative activation of motor proteins revealed by bioimaging and a high-speed
      optical tweezer].

PMID- 24864446
TI  - [Genome dynamics revealed by single-molecule imaging and computer simulation].

PMID- 24864447
TI  - [Construction and control of synthetic genetic circuits].

PMID- 24864448
TI  - [Creation and manipulation of an artificial cellular system].

PMID- 24864449
TI  - [Reaction mechanism of pyridoxal enzymes].

PMID- 24864450
TI  - [Regulation of the vitamin E level in the body by alpha-TTP, alpha-tocopherol
      specific transfer protein].

PMID- 24864451
TI  - [Detailed reaction mechanism of thioacetal forming enzyme, Ecm18].

PMID- 24864452
TI  - [Structure and function of the MCM family proteins].

PMID- 24864453
TI  - [The role of the phosphoinositide metabolism in epidermis].

PMID- 24864454
TI  - [Meigo, an endoplasmic reticulum protein controls the amount and quality of
      membrane proteins regulating dendrite targeting].

PMID- 24864456
TI  - [Contribution of Nrf2 to stress response and metabolic reprogramming in cell
      proliferation].

PMID- 24864455
TI  - [Gene regulation of the proteasome recovery pathway by the transcription factor
      Nrf1 (NFE2L1)].

PMID- 24864457
TI  - [Functions of the FET protein family in health and disease].

PMID- 24864458
TI  - [Visualization of protein secretion by video-rate bioluminescence imaging].

PMID- 24864459
TI  - [New insights into the roles of secreted phospholipase A2s in immunity].

PMID- 24864460
TI  - [Clinical diagnosis progress and continuing medical education].
AB  - The paper discusses current approaches to diagnosing in an internal medicine
      clinic and to improving diagnostic tactics. It gives prospects for training
      physicians in current diagnostic approaches in the framework of the continuing
      medical education system.

PMID- 24864461
TI  - [Prognostic value of detection of arterial hypotensive episodes in patients with
      chronic heart failure].
AB  - AIM: To define the prognostic value of arterial hypotension (AH) episodes in
      patients with chronic heart failure (CHF). SUBJECTS AND METHODS: One hundred and
      ninety-nine patients (mean age 57.2 +/- 10.5 years) were examined. Functional
      Class I, II, III, and IV CHF was diagnosed in 24, 92, 82, and 1 patients,
      respectively. The cause of CHF was coronary heart disease concurrent with
      hypertensive disease in 160 patients. AH was diagnosed when their blood pressure
      (BP) was < or = 100/60 mm Hg during medical visits and daytime BP < or = 100/60
      mm Hg and nocturnal BP < or = 85/47 mm Hg were measured during 24-hour BP
      monitoring (BPM). The follow-up lasted 24 months. The major end-point was a
      combined measure of death rates from any cause, incidence rates of myocardial
      infarction (MI) or stroke. RESULTS: AH was identified in 6.5% of the patients
      with CHF when BP was measured during their medical visit; 24-hour BPM revealed
      hypotensive episodes in 65.8%. There were no differences in the major endpoint in
      relation to the presence of AH episodes. MI developed only in patients with
      systolic AH episodes (5 versus 0 patients; chi2 = 5.55; p = 0.02) and the risk of
      MI was associated with the greater magnitude of diastolic AH. CONCLUSION: 24-hour
      BPM can substantially increase the detection rate of potentially dangerous BP
      changes. Almost three fourths of patients with CHF were observed to have AH
      episodes during a day. The use of angiotensin-converting enzyme (ACE) inhibitor/
      diuretic, ACE inhibitor/mineral corticoid receptor antagonist, ACE
      inhibitor/nitrate combinations in the treatment of patients with CHF increase the
      risk of transient AH. In patients with CHF, the risk of MI is associated with the
      detection of systolic AH episodes and the magnitude of diastolic AH.

PMID- 24864462
TI  - [A poor outcome prediction scale in ST-segment elevation myocardial infarction
      patients undergoing emergency percutaneous coronary intervention].
AB  - AIM: To make a prediction scale using a set of clinical and laboratory prognostic
      variables for patients with ST-segment elevation myocardial infarction (STEMI) on
      their electrocardiograms (ECG) who have undergone percutaneous coronary
      intervention. SUBJECTS AND METHODS: The study enrolled 154 STEMI patients who had
      undergone percutaneous coronary angioplasty with stenting of the artery supplying
      blood to the area of an ischemia. Enzyme immunoassay was used to determine the
      levels of cytokines and selectins on days 1 and 10. RESULTS: During a year, the
      authors identified the following independent risk factors of a poor outcome (PO):
      symptoms of Killip Class III-IV heart failure; a history of smoking; rhythm and
      conduction disturbances on day 1 of the disease; tumor necrosis factor-alpha
      levels determined on day 1 of the disease; IL-1alpha and sP-selectin levels
      measured on day 10. In the made prediction scale, a score was assigned to each
      independent prognostic variable to estimate the risk of PO. The borderline values
      of summing the scores, which divided the patients into groups at low, moderate,
      and high risk for PO, were determined for the practical application of the scale,
      by using the receiver operating characteristic curve (ROC) analysis. The
      performance of the model was tested using an independent sample of STEMI patients
      (n = 50). The probability that the classification of the model was correct
      amounted to 89.6% (p < 0.0001). CONCLUSION: The made prediction scale allows the
      patients with STEMI to be allocated to groups at low, moderate, high risks for PO
      during a year. Evaluation of the prognostic efficiency of the new scale versus
      the known scales PAMI, CADILLAC, and TIMI ST elevation, by plotting the ROC curve
      and estimating the area under the latter, demonstrated the high predictive
      ability of the new scale.

PMID- 24864464
TI  - [Problems in the diagnosis of acute kidney injury in patients with ST-segment
      elevation myocardial infarction].
AB  - AIM: To estimate the frequency and severity of acute kidney injury (AKI) in
      patients with ST-segment elevation acute myocardial infarction (STSEAMI), to
      specify whether the changes in diuresis and serum creatinine levels are equally
      sensitive diagnostic criteria for AKI, and to define their prognostic value.
      SUBJECTS AND METHODS: Three hundred and nineteen patients (249 (78%) men and 70
      (22%) women; age 58 +/- 10 years) with STSEAMI who received thrombolytic therapy
      (TLT) were examined. The diagnosis of STSEAMI, indications for and
      contraindications to TLT, evaluation of its efficiency were made in accordance
      with the All-Russian Scientific Society of Cardiology guidelines (2007). AKI was
      diagnosed and classified using the KDIGO guidelines (2012). RESULTS: AKI was
      diagnosed in terms of diuresis, calculated creatinine levels, and creatinine
      level changes in 107 (34%), 73 (23%), and 68 (22%) patients, respectively. Among
      the patients with AKI diagnosed in view of diuresis, in-hospital death rates were
      higher than in those without AKI (chi2 = 25.46; p < 0.001); the similar pattern
      was seen in patients with AKI diagnosed in terms of calculated creatinine levels
      (chi2 = 3.99; p = 0.045). Logistic regression analysis indicated that regardless
      of gender, age, and time interval between onset of clinical manifestation and
      hospital admission, the in-hospital death rates were associated with the presence
      of AKI in view of diuresis (relative risk 14; 95% confidence interval, 4.03 to
      52.08; p < 0.001). CONCLUSION: The STSEAMI patents receiving TLT exhibited a high
      rate of AKI. The major problem in the early detection of AKI is associated with
      difficulties in the differential diagnosis of AKI and chronic kidney disease. AKI
      diagnosed in view of diuresis is of greater prognostic value for in-hospital
      mortality than that diagnosed in terms of creatinine levels. The diagnosis of
      renal dysfunction in view of basal creatinine levels is prognostically important
      despite the fact that this cannot differentiate AKI from chronic kidney disease
      in the early stage.

PMID- 24864463
TI  - [Analysis of genotype combinations at the polymorphic points of the promoter
      regions of the genes of three matrix metalloproteinases and the gene of vascular
      endothelial growth factor (VEGF) in patients with history of acute myocardial
      infarction].
AB  - AIM: To analyze the association of the promoter polymorphism of the genes of the
      matrix metalloproteinases (MMP) MMP2 (-1306), MMP3 (-1171), and MMP9 (-1562) and
      two vascular endothelial growth factor (VEGF) gene regulatory regions (-2578,
      +936) with the development of myocardial infarction (MI). MATERIALS AND METHODS:
      DNA was analyzed in 251 patients with a history of MI. Five polymorphic positions
      were genotyped by restrictase analysis of amplification products, by using
      specific primers. RESULTS: In addition to the MMP3 5A5A monogenotype, there were
      4 complex genotypes that were significantly different between two analyzed groups
      and positively associated with acute coronary syndrome. Among them, each of two
      genotypes included 2 polymorphic positions; two genotypes did 3 analyzed
      polymorphic positions. Four complex (two-locus (n = 1), three-locus (n = 2), four
      locus (n = 1) genotypes that were negatively associated with MI were also
      identified. CONCLUSION: These findings are evidence in favor of our assumption
      that the increasing number of genotypes as part of the analyzed combined genetic
      complexes detectable in one patient considerably enhances the clinical
      significance of the results of immunogenetic analysis.

PMID- 24864465
TI  - [Use of meldonium in the combination treatment of patients with heart failure in
      the early postinfarction period].
AB  - AIM: To evaluate the impact of 10-14-day intravenous administration of meldonium
      as part of combination therapy in patients with chronic heart failure in the
      early post-infarction period on the recovery period, structural and functional
      parameters, and heart rate variability (HRV). SUBJECTS AND METHODS: The
      investigation enrolled 60 patients (men and women) aged 45 to 75 years at weeks 3
      4 after post-myocardial infarction with symptoms of Functional Class II-III heart
      failure. All the patients underwent 24-hour electrochocardiography monitoring,
      cardiac echocardiography, and HRV study. After dividing the patients into 2
      groups, Group 1 (a study group) (n = 30) was given intravenous meldonium
      (idrinol) 1000 mg/day in addition to the basic therapy of coronary heart disease.
      The patients in the study and control (Group 2; n = 30) groups were at baseline
      matched for age, gender, disease severity, and basic therapy pattern. RESULTS:
      Following 10-14 days of treatment, both groups showed clinical improvement and
      the favorable changes in cardiac structural and functional parameters and HRV
      values, which were more pronounced in the patients receiving meldonium.
      CONCLUSION: The patients with CHF using meldonium as part of combination therapy
      in the early post-infarction period were observed to have clinical improvement, a
      significant reduction in the rate of angina attacks and in the need for nitrates,
      a decrease in the number of arrhythmic and ischemic episodes, and favorable
      changes in cardiac structural and functional parameters and HRV values.

PMID- 24864466
TI  - [Significance of the morphogenetic proteins FGF-23 and Klotho as predictors of
      prognosis of chronic kidney disease].
AB  - AIM: To study the role of the morphogenetic proteins FGF-23 and Klotho in the
      progression of chronic kidney disease (CKD) and in the development of
      cardiovascular events, inflammation, protein-energy deficiency, and other
      complications. SUBJECTS AND METHODS: Examinations were made in 70 patients with
      Stages I-VD CKD: 41 with chronic glomerulonephritis (including 10 with nephritis
      in the presence of diffuse connective tissue diseases), 22 with
      tubulointerstitial nephritis, and 7 with hypertensive nephrosclerosis. There were
      a total of 30 men and 40 women whose age was 20 to 84 years; the mean age at the
      study inclusion was 41 +/- 6.7 years. The serum levels of FGF-23 (Human FGF-23
      ELISA kit using monoclonal antibodies to complete molecule of FGF-23) and Klotho
      (Human alpha-K1 ELISA using anti-Klotho antibodies) were investigated in all the
      70 patients with CKD. RESULTS: The sera of all the examinees with CKD showed
      elevated FGF-23 and decreased Klotho levels, the magnitude of a change in which
      increased from Stage I to VD. In patients with different stages of CKD, the
      increase in FGF-23 levels, as glomerular filtration rate reduced, outstripped
      that in the serum levels of phosphorus and intact parathyroid hormone. There was
      a strong correlation of the serum level of the morphogenetic proteins, Klotho in
      particular, with proteinuria, C-reactive protein level, protein-energy
      deficiency, indicating the pleiotropic effects of these proteins. There was also
      a strong correlation between serum Klotho and ferritin levels and transferrin
      saturation percentage, which suggests that Klotho may be involved in iron
      regulation. CONCLUSION: The results of the investigation lend credence to the
      experimental and clinical findings that the serum levels of the morphogenetic
      proteins FGF-23 (an increase) and Klotho (a decrease) are early markers for
      progressive CKD and that their changes begin just in Stage III CKD and progress
      as renal failure worsens.

PMID- 24864468
TI  - [Tactics for the correction of intestinal microbiocenotic disorders in the
      combination therapy of patients with chronic liver diseases].
AB  - AIM: To evaluate the efficacy of the symbiotic Linex used in the combination
      therapy of liver cirrhosis (LC). SUBJECTS AND METHODS: Seventy-four patients with
      LC, including 44 who received additionally the symbiotic Linex and 30 who had
      conventional therapy, were examined. All the patients underwent clinical and
      biochemical blood tests, abdominal ultrasonography, fecal test for bacteria, gas
      chromatography-mass spectrometry of the blood composition of microbial markers,
      number connecting test, and quality-of-life assessment (SF-36). RESULTS: The
      symbiotic-treated patients showed a significant improvement in biochemical
      parameters (decreases in transaminase activities, bilirubin levels, hepatic
      protein-synthetic function--there were elevations in the concentrations of total
      protein from 74.0 +/- 0.50 to 78.1 +/- 0.80 g/l (p < 0.05) and albumin from 30.6
      +/- 1.7 to 35.5 +/- 1.6 g/l (p < 0.05). There were also increases in the count of
      bifidobacteria from 8.7 +/- 0.1 to 9.1 +/- 0.1 Ig CFU/g (p < 0.05), lactobacilli
      from 5.0 +/- 0.2 to 5.2 +/- 0.2 Ig CFU/g (p < 0.05) and in the total count of
      Escherichia coli from 7.6 +/- 0.3 to 7.9 +/- 0.3 Ig CFU/g (p < 0.05); a tendency
      for normalization of microbial markers was revealed by mass spectrometry; the
      manifestations of hepatic encephalopathy were alleviated (the number connecting
      test showed a reduction from 51.0 +/- 3.58 to 29.7 +/- 4.10 sec (p < 0.05)), and
      the quality of life improved. CONCLUSION: By normalizing enteric microbiocenosis,
      the symbiotic Linex positively affects the course and prognosis of LC and it is
      both a symptomatic and pathogenetic agent for the treatment of patients.

PMID- 24864467
TI  - [Endothelial dysfunction gene polymorphisms and the rate of liver fibrosis in
      chronic hepatitis C].
AB  - AIM: To assess the association of the CYBA, NOS3, and MTHFR gene polymorphisms
      and a rate of fibrosis progression in chronic hepatitis C (CHC). SUBJECTS AND
      METHODS: One hundred and nine CHC patients with the verified stage of liver
      fibrosis and cirrhosis at its onset were examined. The disease duration was
      determined in all the patients and additional risk factors of liver lesion were
      absent. A group of rapidly progressive fibrosis comprised 55 patients with a
      calculated fibrosis progression rate of 0.130 fibrosis units/year or higher and
      54 patients with a progression rate of less than 0.130 fibrosis units/year were
      assigned to a slow fibrosis group. A compression group consisted of 299 healthy
      blood donors. The polymorphism of the genes under study was determined by
      polymerase chain reaction-restriction fragment length polymorphism analysis.
      RESULTS: The mutant TT genotype of the CYBA gene was significantly more common in
      the CHC patients with rapidly progressive fibrosis than in those with slowly
      progressive fibrosis (odds ratio for TT 9.09 at 95% confidence interval, 1.09 to
      74.83; p = 0.0161). No significant differences were found in the distribution of
      the alleles and genotypes of the NOS3 and MTHFR genes between the groups of
      patients with slowly and rapidly progressive fibrosis. CONCLUSION: The findings
      make it possible to regard the TT genotype of the CYBA gene from the C242T locus
      as profibrogenic and as one of the markers of the poor course of CHC.

PMID- 24864469
TI  - [Role of platelets in the pathogenesis of Coxiella infection].
AB  - AIM: To determine the relationship of hemostatic disorders to the direct impact
      of Coxiella burnetii on platelets as one of the key mechanisms of the
      pathogenesis of Q fever. SUBJECTS AND METHODS; Platelet functional activity,
      plasma hemostatic parameters, von Willibrand factor (vWF) were investigated; and
      polymerase chain reaction assay was used to determine C. burnetii DNA in the
      leukocyte and platelet sediments of 41 patients aged 39.9 +/- 0.8 years diagnosed
      with Q fever at the Astrakhan Regional Clinical Hospital in 2009 to 2010.
      RESULTS: The examinees were recorded to have hemorrhagic phenomena (34.7%) as a
      hematoma (27.2%), gingival (2.4%) and nasal (9.2%) hemorrhages, vomiting blood
      streaks (3.4%), melena (4.5%), roseolous-papular (22.1%) and hemorrhagic (9.3%)
      rashes on the skin. Examination of hemostasis revealed thrombocytopenia and
      platelet hypoaggregation, increased plasma fibrinogen homeostasis, and
      significantly elevated vWF during convalescence. C. burnetii genomic DNA was
      isolated from platelets in all the examinees, from leukocytes and platelets in
      78% of cases and only from platelets in 22%. A fluorescence signal indicating the
      pathogen genome was more early recorded in 54.8% of cases in the platelets than
      in the leukocytes. CONCLUSION: At week 1 of the disease, the absence of
      significant plasma hemostatic changes and the retention of the control level vWF
      with the lower count of platelets and their aggregatory activity suggest that the
      platelets are able to interact with this pathogen, which is confirmed by the
      results of genodiagnosis of this rickettsiosis with the pathogens being isolated
      from the platelet sediment. The determination of platelet aggregatory activity is
      a primary diagnostic test to detect disorders in the hemostatic system. The
      higher detection rate of C. burnetii genomic DNA from the platelets than from the
      leukocyte sediment can recommend that platelets be used as biological material in
      the diagnosis of Q fever.

PMID- 24864470
TI  - [Impact of pharmacogenetic testing on the risk of bleedings and excessive
      hypocoagulation episodes in the use of warfarin: the first meta-analysis of
      Russian prospective studies].
AB  - AIM: To perform a meta-analysis of Russian prospective studies comparing the
      pharmacogenetic versus conventional warfarin dosing procedures. MATERIALS AND
      METHODS: Publications were sought in the PubMed and eLibrary through September
      30, 2013. Seven prospective studies comparing the pharmacogenetic method of
      warfarin dosing with consideration for CYP2C9, VKORC1, and CYP4F2 gene
      polymorphisms with the conventional one were selected. The number of minor and
      major bleedings and hypocoagulation episodes was taken into account. The meta
      analysis was performed using MIX Pro 2.0. RESULTS: Six studies compared the
      number of bleedings in experimental and control groups. Analysis of statistical
      heterogeneity showed that extraneous factors did not influence the results of
      meta-analysis. The pharmacogenetic approach decreases the risk of bleeding. The
      pooled odds ratio (OR) was significant for minor (OR = 0.49; 95% confidence
      interval (CI), 0.31 to 0.78; p = 0.002), major (OR = 0.07; 95% CI, 0.008 to 0.54;
      p = 0.01) and both minor and major bleedings (OR = 0.49; 95% CI, 0.31 to 0.78; p
      = 0.002). Six studies estimated the number of hypocoagulation cases. There was no
      evidence for statistical heterogeneity (Q-test p = 0.13; I2 = 40%). Four studies
      showed a group difference in the number of hypocoagulation cases (p < 0.05). The
      pooled OR was 0.21 (95% CI, 0.15 to 0.3; p < 0.01). The pharmacogenetic dosing
      groups had fewer hypocoagulation episodes than the control ones. CONCLUSION: The
      pharmacogenetic approach decreases the risk of bleeding and the episodes of
      hypocoagulation. The performed meta-analysis covered only two randomized trials.
      Improving the metalogic quality and statistical power of Russian studies will be
      able to get more reliable data on the impact of pharmacogenetic testing on
      clinical outcomes during warfarin therapy.

PMID- 24864471
TI  - [A case of diagnosis of asymmetric apical hypertrophic cardiomyopathy of the left
      ventricle with intraventricular obstruction].
AB  - The paper describes a case of diagnosis of one of the rare forms of myocardial
      hypertrophy--asymmetric hypertrophic cardiomyopathy with isolated hypertrophy of
      the cardiac apex (an apical form) and intraventricular obstruction. It discusses
      problems in the diagnosis of rare forms of hypertrophic cardiomyopathy.

PMID- 24864472
TI  - [A clinical case of diagnosis of left ventricular noncompaction myocardium in a
      patient with infectious myocarditis].
AB  - The paper describes a rare clinical case involving primary cardiomyopathy
      (noncompaction of the left ventricular myocardium (NCLVM), infectious
      myocarditis, and, possibly, hypertrophic cardiomyopathy (HCM). Objective,
      laboratory instrumental, invasive examination (coronarography with right
      ventricular endomyocardial biopsy) of the patient and histological study of his
      heart biopsy revealed acute infectious myocarditis concurrent with NCLVM and,
      possibly, HCM. The detection of a rare abnormality as NCLVM necessitates a
      meticulous additional examination to identify other primary cardiomyopathies
      (including HCM).

PMID- 24864473
TI  - [Wilson-Konovalov disease in 3 sisters: a radical change in prognosis if timely
      diagnosed].
AB  - Wilson-Konovalov disease is a rare autosomal recessive genetic disorder in which
      copper accumulates in the liver, brain and other target organs. The paper
      describes a family case of the abdominal form of the disease in three sisters,
      the eldest of them died from fulminant liver failure at the age of 18 years. The
      second sister aged 16 years was diagnosed as having the disease at the stage of
      decompensated liver cirrhosis; her treatment with D-penicillamine resulted in
      complete disease remission. The youngest sister was diagnosed with the disease at
      the preclinical stage, which could expect its good prognosis. However, the
      patient's refusal of treatment led to death from liver failure. This case
      demonstrates the importance of timely diagnosis and the possibility of dramatic
      improvement in prognosis even at the stage of decompensated liver cirrhosis.

PMID- 24864474
TI  - [Itching: differential diagnosis and therapy].
AB  - The lecture deals with the differential diagnosis and treatment of diseases
      accompanied by itching. It considers the major components of its pathogenesis,
      which are important to provide a rationale for its therapy. Particular emphasis
      is laid on the analysis of the most common classifications of the causes of
      itching, which take into account both pathogenetic and clinical parameters. The
      main differentially diagnostic signs of dermal and nondermal diseases attended by
      itching are given. Antihistamines among the agents intended for itching therapy
      are considered in detail. The efficacy and safety of first- and second-generation
      antihistamines, including quinuclidine derivatives, are comparatively analyzed.

PMID- 24864475
TI  - [Role of the determination of aortic pressure and rigidity in patients with
      cardiovascular diseases].
AB  - The paper reviews the literature on studies of the structural and functional
      properties of great arteries in patients with cardiovascular diseases. It
      analyses the pathophysiological components of the formation of central blood
      pressure (BP) and describes current registration procedures. The negative aspects
      of the impact of elevated central BP on target organs are considered. The
      prognostic and clinical values of the indicators of central arterial stiffness
      are demonstrated.

PMID- 24864476
TI  - [Evolution of ideas on the assessment of cardiovascular risks in the
      perioperative period].
AB  - Substantial advance has been made in operative surgery and anesthesiology; on the
      one hand, population ageing and, on the other, increasing surgical care needs
      make the prediction of perioperative complications an important component of the
      entire current model of surgical care. In the last decades, the concept of risk
      in perioperative medicine has been formulated; the theoretical base for a
      statistical description of the risk concept has been created, and different
      integral risk prediction models based on the risk index obtained by regression
      analysis have been elaborated and promoted. At the same time, none of the created
      models can reliably assess the risk of cardiovascular events associated with
      surgical intervention and predict the probability of poor clinical outcomes with
      a high degree of accuracy.

PMID- 24864477
TI  - [Dabigatran in the prevention of stroke in nonvalvular atrial fibrillation:
      complex clinical situations and real clinical practice].
AB  - It is well known that there is a 5-fold increase in the incidence of strokes and
      systemic thromboembolic events in atrial fibrillation (AF) and anticoagulant
      therapy considerably reduces the risk of their development. Until recently,
      warfarin has been mainly used for this purpose. Dabigatran is the first
      representative of new-generation oral anticoagulants from a class of direct
      thrombin inhibitors to treat nonvalvular AF. Unlike warfarin, the drug provides a
      predictable and steady-state anticoagulant effect. This review presents the main
      pharmacological characteristics of dabigatran, the possibilities of its use in
      complex clinical situations in patients with AF in cardioversion, ablation,
      surgical/invasive interventions, hemorrhage, myocardial infarction, and stroke,
      as well as data on the use of the drug in real clinical practice.

PMID- 24864478
TI  - [Alcoholic liver disease: current state of the problem].
AB  - The literature review gives the present views of the diagnosis and treatment of
      alcoholic liver disease (ALD) and data on the genetic markers associated with the
      development of ALD and alcohol addiction. It discusses in detail the mechanisms
      of liver damage within the disease in question and substantiates indications for
      the use of prednisolone and pentoxifylline in alcoholic hepatitis. Therapeutic
      approaches to treating different forms of ALD are considered.

PMID- 24864479
TI  - [Current views on the role of probiotics in the prevention and treatment of
      different diseases: focus on Linex].
AB  - The paper gives documentary information on the role of probiotics in the therapy
      of different diseases and recommendations for their use. The efficacy and safety
      of the combined probiotic Linex are discussed on the basis of the results of
      clinical trials.

PMID- 24864480
TI  - [Antibacterial therapy for acute cystitis in the age of growing pathogen
      resistance].
AB  - Acute cystitis refers to uncomplicated lower urinary tract infections, with the
      recurrence rates after the first cystitis episode being 50%. The basic treatment
      for the above diseases is antibacterial therapy, whose efficiency depends
      entirely on the right choice of a drug during initial empiric therapy. The paper
      gives the European Association of Urology guidelines and Russian guidelines,
      which are based on the results of both international (ARESC) and Russian (DARMIS)
      studies of urinary tract infection pathogens and their susceptibility to
      antibacterial drugs. Phosphomycin trometamol and furasidine potassium are the
      drugs of choice to treat acute cystitis in Russia now.

PMID- 24864481
TI  - [The effectiveness of comprehensive rehabilitation of the patients presenting
      with coronary heart disease with the application of underwater shower massage and
      electrical stimulation].
AB  - The underwater shower massage and electrical stimulation were applied to treat
      120 patients presenting with coronary heart disease. The estimation of the
      effectiveness of this treatment with the use of functional diagnostic methods
      revealed its psychocorrective effect manifested in the form of reduced frequency
      and duration of painful and painless angina seizures, restricted sympathetic
      influences on the heart as well as normalized sympathovagal balance, lipid
      status, antioxidative system, central and peripheral hemodynamics, improved
      systolic and diastolic function of the myocardium, enhanced tolerability of
      mental, emotional, and physical workload. The study allowed the predictors of the
      effectiveness of therapeutic and health-promoting measures to be identified.

PMID- 24864482
TI  - [The effectiveness and safety of the balneotherapeutic treatment of the
      mechanical transport drivers suffering heart rhythm disorders].
AB  - AIM: To estimate the effectiveness and safety of the balneotherapeutic treatment
      of the of mechanical transport drivers (MTD) suffering heart rhythm and cardiac
      conduction (HR&CC) disorders with concomitant arterial hypertension (AH) treated
      based at a Nalchik health resort. MATERIAL AND METHODS: A total of 42 MTD (all
      men) presenting with HR&CC disorders and I-II grade AH were admitted for the
      balneotherapeutic treatment at a Nalchik health resort using two main approaches,
      viz. (a) thermal nitrogen mineral baths 36-37 degrees C in the form of 22 courses
      consisting of 8-10 sessions each (10-15 min every other day) and (b) bromine
      iodine mineral baths 36-37 degrees C in the form of 20 courses consistingof 8-10
      sessions each (10-15 min every other day). The outcomes of the treatment were
      estimated based on the results of general clinical examination and laboratory
      analyses supplemented by round-the-clock monitoring of arterial pressure and ECG,
      psychological and psychophysiological testing (PPT). RESULTS: The results of
      clinical and instrumental investigations into dynamics of the general health
      status, peripheral and coronary hemodynamics in the drivers with HR&CC disorders
      and AH give evidence of the improvement of their psychosomatic status following
      the treatment with the use ofthermal nitrogen and bromine-iodine mineral baths in
      86.4 and 80.0% of the cases, respectively. In the subjects of the former group,
      significant changes in the dynamic response system were documented. 75% of MTD
      included in the latter group were characterized by the absence of improvement of
      professionally significant functions and skills that were found to deteriorate in
      the remaining 25%. CONCLUSION: The balneotherapeutic treatment of MTD presenting
      with HR&CC disorders and I-II grade AH with the use of thermal nitrogen mineral
      baths proved to be a highly effective, specific, and safe method in 86.4% of the
      cases. The use of bromine-iodine mineral baths resulted in clinical and
      hemodynamic changes of the psychosomatic status in 80.0% of the drivers
      concomitant with the deterioration of their professional activities. It is
      concluded that PPT is mandatory for the mechanical transport drivers presenting
      with HR&CC disorders and I-II grade AH before they resume their professional
      activities after the balneotherapeutic treatment.

PMID- 24864483
TI  - [Comprehensive rehabilitation of the subjects presenting with occupational
      muscular-skeletal abnormalities].
AB  - The methodological approach to the rehabilitative treatment of the subjects
      presenting with occupational muscular-skeletal abnormalities in the upper limb
      girdle associated with their occupational activities implies the combined
      application of a pulsed magnetic field, therapeutic peloids and ultrasound
      therapy to the neuromuscular apparatus and tendinous-capsular structures of the
      rotator cuff undergoing dystrophic degeneration. This therapeutic modality makes
      it possible to improve the biomechanical conditions of the patients by broadening
      the range of active painless movements in the affected shoulder joint by 42% (p <
      0.05), normalizing tonal and load-bearing characteristics of the muscles
      (increase of the initially reduced muscular tone at rest by 27% (p < 0.05) at a
      maximum voluntary tension (16%, p > 0.05), changing trophicity of periarticular
      tissues (elevation of the pain sensitivity threshold of tendons and painful
      indurations in the functionally active muscles of the thoracic girdle of the
      upper extremity by 76% (p < 0.05). It is concluded that these changes contribute
      to the improvement of professional activities of the patients.

PMID- 24864484
TI  - [The experience with the application of dynamic electroneurostimulation in
      clinical medicine. A multicenter study].
AB  - The ever growing occurrence of iatrogenic pathologies under present conditions is
      responsible for the high percentage of adverse reactions associated with
      medicamental therapy. It emphasizes the necessity of the more extensive
      application of non-pharmacological products and physiotherapeutic methods free of
      this disadvantage. Dynamic electroneurostimulation (DENS) is one of the up-to
      date promising therapeutic and prophylactic modality for this purpose by virtue
      of its broad spectrum of action. This approach is based on the principle of
      monitoring skin surface impedance. The present study was designed to estimate the
      effectiveness of DENS for the treatment of the patients presenting with chronic
      diseases, such as nervous disorders, dysfunction of the locomotor system,
      gastrointestinal and urogenital pathologies. This multicenter study in the form
      of a randomized clinical trial included 1,198 outpatients and 814 inpatients. It
      was shown that the application of dynamic electroneurostimulation provides a
      highly efficacious tool for the management of nervous, internal, and other
      diseases. It can be recommended for use as a promising non-medicamnetal
      therapeutic modality for the combined treatment and rehabilitation of the
      patients presenting with the diseases of various etiology.

PMID- 24864485
TI  - [The role of magnetolaserotherapy in the correction of the adaptive potential of
      the brain in the children suffering absence seizures].
AB  - We have conducted a course of magnetic laser therapy targeted on the vegetative
      structures at the neck of the children suffering absence seizures in an attempt
      to optimize the functioning of the non-specific brain structures. The study has
      demonstrated that such treatment promotes normalization of the components of the
      orientation response to sound almost to the level observed in the healthy
      children. The alpha-index returned to the normal value as well.

PMID- 24864487
TI  - [The rehabilitative treatment of the frequently ill children presenting with
      chronic infectious foci in the nasopharynx].
AB  - AIM: The objective of the present study was to elucidate the influence of the
      combined physiotherapeutic remedial treatment on the effectiveness of
      rehabilitation of the frequently ill children (FIC) and children presenting with
      chronic infectious foci inthe nasopharynx taking into consideration their
      microelemental and immunological status. MATERIALS AND METHODS: A total of 80
      frequently ill children and children presenting with chronic infectious foci
      inthe nasopharynx were available for the observation with special reference to
      dynamics of clinical conditions, immunological processes, and microelement
      composition. CONCLUSION: The combined treatment including the intake of
      "Asonovklyuch" mineral water enhanced the resistance of the children to the
      causative factors of respiratory infections and increased selenium content in
      their body. It is concluded that the treatment of the children presenting with
      chronic infectious foci inthe nasopharynx with the use of the specialized dietary
      product "Clinutren Junior" produces an anti-inflammatory and immunoregulatory
      effect and thereby promotes the correction of disorders of microelement
      nutrition.

PMID- 24864486
TI  - [The immediate and long-term results of sylvinite speleoclimatotherapy in the
      children presenting with pollinosis].
AB  - The present open randomized comparative study had the objective to compare the
      effectiveness of two strategies for the treatment of early spring pollinosis in
      23 children at the age varying from 2 to 17 years in the phase of exacerbation.
      The patients of the study group underwent 10 sessions of sylvinite
      speleoclimatotherapy 60 min in duration each in addition to conventional
      pharmacotherapy. The children included in the control group were treated by
      traditional medicamental therapy alone. The estimation of clinical symptoms on
      day 10 after the onset of the treatment with the use of a scoring system has
      demonstrated a marked decrease in the severity of allergic rhinitis (p = 0.003),
      conjunctivitis (p = 0.01), and the total number of signs and symptoms of the
      disease (p = 0.002) in the children managed with the use of sylvinite
      speleoclimatotherapy. Positive dynamics in the patients of the control group was
      less pronounced (p < 0.05). The aeropollinological data are presented giving
      evidence of the absence of a high pollen concentration in the air of the
      speleoclimatic chamber and its high content in the atmospheric air at the height
      of thepollen season of early spring allergens. The clinical manifestations of the
      allergic conditions were shown to depend on the concentration in the atmospheric
      air of the causative allergens from their principle plant sources (r = 0.66, p =
      0.039 in the control patients in comparison with r = 0.42, p = 0.22 in the
      children treated by sylvinite speleoclimatotherapy. It is concluded that the
      results of the present study confirm the clinical effectiveness of sylvinite
      speleoclimatotherapy used in the acute phase of pollinosis. The combination of
      this modality with traditional medicamental therapy accelerates elimination of
      clinical symptoms of allergic rhinitis and conjunctivitis; moreover, it reduces
      the frequency of recurrent respiratory disorders.

PMID- 24864488
TI  - [The clinical results and lipid peroxidation dynamics in the patients presenting
      with psoriasis treated by the applications of a natural highly mineralized
      bromine-iodine brine].
AB  - The authors report the results of the treatment of 64 patients presenting with
      psoriasis by the applications of a natural highly mineralized bromine-iodine
      brine. The method has been shown to be highly efficacious and safe. It allowed
      the clinical remission and marked improvement of the patients' clinical
      conditions to be achieved in 48 (77.4%) cases compared with 10 (27.8%) cases
      among the patients of the control group. Exacerbation was documented in a single
      patient with psoriatic erythrodermia. All the patients showed the normal results
      of general and biochemical clinical analyses of blood and urea throughout the
      study period. The applications of the natural highly mineralized bromine-iodine
      brine exerted the normalizing action on seven of the 8 characteristics of the
      lipid peroxidation process. It is maintained that the high effectiveness of the
      method in question can be accounted not only by the reflectory and humoral
      mechanisms of action of highly mineralized bromine-iodine brine but also by the
      marked exhaustion of the functional reserves of the mast cells under effect of
      the applications. It is concluded that an advantage of the proposed approach over
      standard balneotherapeutic procedures consists of the possibility to employ it
      not only at the base of a spa and health resort facility but also in a different
      setting with the involvement of the patients suffering from progressive
      psoriasis.

PMID- 24864489
TI  - [Comparative analysis of the methods for the estimation of the biological age].
AB  - The present article was designed to report the results of comparative analysis of
      the methods for the estimation of the biological age based on the measurement of
      a number of anthropometric and functional characteristics in the relatively
      healthy persons at the age varying from 30 years to 75 years. The study involved
      277 individuals (143 women and 134 men). All the patients underwent clinical,
      biochemical, hormonal and instrumental examination. The following two methods
      were used to determine the biological age of the participants of the study: the
      ontogenetic anthropometrical method (L.M. Belozerova, 1999) and the Kiev method
      (V.P. Voytenko, 1984). These mathematical models are based on a specific set of
      calculation techniques for each anthropometric and instrumental parameter and
      approximately equally reflect the mismatch between the calendar and biological
      age; however, they are different in the degree of correlation with the
      disturbances of metabolism, enzymatic maintenance of metabolic processes, and
      other parameters. By way of example, the method of L.M. Belozerova for the
      calculation of the anthropometric biological age largely correlates with the
      insulin resistance index, blood concentrations of aldosterone, triglycerides and
      glucose, whereas the results obtained by the method of V.P. Voytenko show
      stronger correlation with the activity of alkaline phosphatase, the ceruloplasmin
      level and self-estimation of the patients' health.

PMID- 24864490
TI  - [The role of local hyperthermia in oncology: applications of a magnetic field,
      laser radiation, and ultrasound].
AB  - This paper reports the principal data on hyperthermia and its role in the modern
      combined treatment of malignant neoplasms. A brief characteristic of magnetic,
      laser, and ultrasound hyperthermia is presented. The prospects for the further
      development of new methods of hyperthermia for the application in oncology.

PMID- 24864491
TI  - [The application of aquaerobic as a form of therapeutic exercises for the
      prenatal preparation of the pregnant women].
AB  - The present review considers aquaerobic as a form of therapeutic exercises for
      the prenatal preparation of the pregnant women. It is shown that aquaerobic
      improves the parameters characterizing the degree of physical preparedness and
      physical development of the pregnant women, normalizes their general well-being,
      mood, sleep, physical activity, and working capacity. Moreover, regular
      aquaerobic exercises prevent the development of pregnancy complications.

PMID- 24864492
TI  - [Hybrid phacoemulsification: a new stage in the improvement of cataract surgery
      (?)].
AB  - PURPOSE: To evaluate the early results of femtosecond laser application in
      phacoemulsification of cataracts of different density. MATERIAL AND METHODS:
      Femtosecond laser-assisted phacoemulsification cataract surgery was performed on
      277 patients (390 surgeries) with II-IV degree lens nuclear density. RESULTS: The
      use of femtosecond laser for capsulorexis and lens nucleus fragmentation enables
      forming of a well-shaped, properly sized, and accurately centered aperture in the
      anterior lens capsule, reduces the equivalent time of ultrasound exposure (by 30%
      in average) and decreases the total time of nuclear fragments emulsification by a
      third. CONCLUSIONS: Femtosecond laser-assisted phacoemulsification is a highly
      effective and safe surgical technique that takes the surgery to a new level. By
      analogy with cardiovascular surgery this direction of improvement of cataract
      treatmentmay be called "hybrid phacoemulsification". Hybrid approach in
      cardiovascular surgery is promising and progressive. It combines the
      possibilities of conventional and minimal invasive endovascular surgery,
      considerably reducing intraoperative trauma during open-heart procedures. In
      cataract surgery the use of femtosecond laser in combination with classical
      ultrasound phacoemulsification enables closed-eye performance of certain
      technical stages that are usually fraught with complications.

PMID- 24864493
TI  - [Results of fistulizing and Ahmed valve surgery for treatment of refractory
      glaucoma].
AB  - Surgical results of 76 patients (76 eyes) aged 25-79 years with secondary
      refractory glaucoma were analyzed. The best hypotensive effect and visual
      functions integrity were achieved with Ahmed valve implantation (86.7% and 83.3%
      of cases respectively); after conventional fistulizing surgery the hypotensive
      effect was observed in 45.5%, noncompromised vision--in 54.5% of cases. Tunnel
      trabeculectomy with iridocycloretraction led to normalization of intraocular
      pressure and stabilization of visual functions in 81.3% and 68.8% of cases
      respectively and thus can be considered as an alternative to fistulizing surgery
      in patients with secondary refractory glaucoma. Uveal glaucoma is a relative
      contraindication to Ahmed valve implantation, while neovascular glaucoma is that
      to tunnel trabeculectomy with iridocycloretraction.

PMID- 24864494
TI  - [Application fluorescein angiography: a new method for assessment of anterior eye
      segment hemomicrocirculation].
AB  - PURPOSE: To develop a noninvasive fluorescein angiography (FAG) method for the
      anterior eye segment (AES) assessment which would imply using the most-ordered
      site of bulbar conjunctival capillary bed as the object of dye administration.
      MATERIAL AND METHODS: The study enrolled 30 individuals (41 eyes) with no evident
      ocular pathology and significant systemic diseases aged from 18 to 70 years and
      19 patients with uveitis, of whom 10 patients (10 eyes) aged 43-57 had anterior
      uveitis and 9 patients (10 eyes) aged 17-29 had pars planitis. Assessment of
      conjunctival microcirculation was done by the proposed method of fluorescein
      angiography in which the dye is applied to the bulbar conjunctival capillary bed.
      RESULTS: In all cases after a microdose of fluorescein was administered to the
      intermediate zone capillaries it distributed into two venous systems of the AES:
      peripheral and prelimbal venules. Circulation time and vascular permeability
      (depending on the presence or absence of extravasal hyperfluorescence) were
      described. Angiographic patterns in healthy individuals and patients with either
      clinical form of uveitis appeared to differ considerably. CONCLUSIONS: Findings
      of the proposed noninvasive application FAG reflect the state of capillary and
      venular components of bulbar conjunctival microcirculatory system. Sings of
      increased hemoperfusion of the AES and vascular permeability were seen in
      patients with acute anterior uveitis, whereas in pars planitis patients vascular
      hyperpermeability was associated with decreased hemoperfusion of the AES. The
      proposed method can be used for monitoring of the inflammatory process in
      anterior and peripheral uveitis.

PMID- 24864495
TI  - [Surgical reconstruction of posttraumatic defects and deformities of the orbit
      using frameless navigation].
AB  - PURPOSE: To explore the possibilities of frameless navigation surgery in patients
      with posttraumatic defects and deformities of the orbit. MATERIAL AND METHODS: In
      order to develop frameless navigation technique for surgical treatment of
      posttraumatic defects and deformities of the orbit, examination and surgery were
      performed on 21 patients of the N.V. Sklifosovsky Research Institute of Emergency
      Medicine. Multi-slice spiral computed tomography was used for preoperative
      simulation and intraoperative control. Virtual layer-by-layer reconstruction of
      missing bone fragments and modeling of anatomical position of dislocated bone
      fragments in frontal, axial, and sagittal images were performed. Implant position
      control was done with pointer device of the navigation system. RESULTS: Good
      functional (disappearance of diplopia in primary position of gaze) and cosmetic
      results were obtained in all patients. None developed complications in the
      postoperative period. CONCLUSIONS: The use of frameless navigation in surgical
      treatment of posttraumatic defects and deformities of the orbit allows to obtain
      good and stable functional and cosmetic results.

PMID- 24864496
TI  - [Modern endothelial keratoplasty-based options for visual rehabilitation of
      patients with bullous keratopathy and concomitant glaucoma].
AB  - PURPOSE: To develop endothelial keratoplasty-based surgical treatment and
      management policy for patients with bullous keratopathy complicated by glaucoma.
      MATERIAL AND METHODS; A total of 41 patients (41 eyes) with bullous keratopathy
      and concomitant II-III stage glaucoma were enrolled. All patients underwent
      endothelial keratoplasty of different modification--DSAEK, utDSAEK, DMAEK. Two
      types of glaucoma drainage surgery were applied--intrascleral amniotic drainage
      and implantation of a domestically manufactured silicone tubular drainage wrapped
      in amnion. RESULTS: Intraocular pressure (IOP) was compensated in 11 of 12
      patients, on whom a glaucoma procedure was performed. In 29 post-keratoplasty
      patients, whose IOP was compensated both before and after the surgery, the mean
      IOP at the 2-year follow-up visit was 2 mm Hg higher than the preoperative
      values. Medication regimen was adjusted in 7 cases in order to enhance the
      hypotensive effect. No evident correlation between graft thickness and IOP change
      was found. CONCLUSION: Based on a study of 41 patients (41 eyes) with bullous
      keratopathy and concomitant glaucoma who underwent endothelial keratoplasty,
      surgical treatment and therapeutic management policy is developed, which takes
      into account whether or not the IOP is compensated and whether or not its further
      decrease is required and implies the use of own original drainage techniques.

PMID- 24864497
TI  - [Life expectancy of patients with primary glaucoma, residents of a large
      industrial city of Siberia].
AB  - PURPOSE: To investigate life expectancy and the structure of causes of death in
      patients with primary glaucoma, residents of a large industrial city of Siberia.
      MATERIAL AND METHODS: The database of the Novokuznetsk Public Health Department
      information analysis center on registration forms 025 (outpatients) and 066
      (inpatients) for 2004-2011 was analyzed. RESULTS: A total of 5424 primary
      glaucoma patients were registered during 2004-2011, of whom 441 (8.1%)
      subsequently died. Age at death of patients with primary glaucoma was 69.0 +/-
      7.2 years. The difference between age at death and at diagnosis of glaucoma was
      2.6 +/- 1.8 years. CONCLUSION: The correlation suggests that primary glaucoma is
      a predicting factor for vascular events, such as stroke or myocardial infarction.
      The authors assume that topical administration of beta blockers without
      consulting a physician and/or a cardiologist may lead to ischemic stroke.

PMID- 24864498
TI  - [Results of infrared diode laser application for iris reconstruction in cases of
      pupillary deformity and displacement in pseudophakic eyes].
AB  - The article studies application possibilities and potency of near infrared
      coagulative radiation of a diode laser for correction of postoperative iris
      defects followed by pupillary deformities and displacement. It is found that the
      use of near infrared diode laser radiation at 0.810 microm enables visual
      improvement through pupil enlargement or its shift to the optical centre. The use
      of the wavelength specified does not cause severe atrophic or cosmetic changes in
      the iris.

PMID- 24864499
TI  - [Giant cavernous hemangioma of the orbit (case report)].
AB  - The following case demonstrates a successful en bloc removal of a massive
      cavernous hemangioma of the orbit via vertical transpalpebral approach with
      postoperative improvement of optic nerve condition and optimal cosmetic result.

PMID- 24864500
TI  - [Uveal schwannoma mimicking melanoma (case report)].
AB  - The article presents a rare clinical case of intraocular schwannoma localized in
      the pre-equatorial choroidea and the pars plana and complicated by secondary
      glaucoma. Prolonged course of the disease and the presence of scleral staphyloma
      allowed to assume benign nature of the tumor. Enucleation was performed due to
      painful secondary glaucoma. Histological examination of the enucleated eye
      revealed a choroidal schwannoma. Despite the absence of pathognomonic signs and
      rare occurence, the possibility of intraocular schwannoma must be kept in mind
      when examining patients for uveal melanoma.

PMID- 24864501
TI  - [Intraocular schwannoma case report: clinical and pathomorphological analysis].
AB  - The paper presents a complete clinical, instrumental, histopathological,
      immunohistochemical, cytological, and molecular-genetic testing of intraocular
      schwannoma in a 13-year-old girl.

PMID- 24864503
TI  - [Use of cyclosporine 0.05% in various ocular surface disorders].
AB  - It is proved that chronic ocular surface inflammatory disease (including allergic
      blepharitis, recurrent chalyazia, punctuate keratitis, recurrent herpetic corneal
      erosions, late stages of adenoviral keratoconjunctivitis, etc.) takes part in the
      development of secondary dry eye syndrome (DES). However, therapies for
      inflammation-induced impairment of tear production do not provide long-term
      control of inflammatory process. Cyclosporine 0.05% eye drops are an option.
      Their effect is well-studied in foreign practice. Local application experience of
      cyclosporine 0.05% eye drops was summarized at a meeting of the Russian expert
      group on DES and conclusions were made on their effectiveness in treatment of dry
      eye syndrome associated with certain ocular surface inflammatory disorders, such
      as allergic blepharoconjunctivitis, late stages of adenoviral
      keratoconjunctivitis, and others.

PMID- 24864502
TI  - [Corneal protection in contact lens users].
AB  - PURPOSE: To evaluate the efficacy of corneoprotective agents (Corneregel and
      Solcoseryl) in contact lens users. MATERIAL AND METHODS: A total of 66 long-term
      contact lens wearers with dry eye symptoms and varying degrees of corneal
      epitheliopathy were monitored. All patients used artificial tears, which,
      however, were not effective enough to suppress manifestations of corneal
      epitheliopathy and to release the associated discomfort. The therapy was
      supplemented with Corneregel. The following examination methods were applied:
      biomicroscopy with fluorescent staining, Norn test, Schirmer's test, advanced
      tearscopy with digital image analysis of the precorneal tear film lipid layer,
      corneal confocal microscopy. In all cases the assessment was performed prior to
      starting Corneregel and repeated in 7 days, 14 days and 1 month. RESULTS:
      Complete corneal re-epithelization and restoration of the most superficial layer
      of the epithelium were achieved within 7-14 days. In case of severe initial
      epitheliopathy the effect of Corneregel was not sufficient and epithelium defects
      remained. These patients additionally received Solcoseryl Eye Gel. After the
      treatment course the condition of corneal epithelium ameliorated and contact lens
      wearing comfort increased. A longer precorneal tear film break-up time indicated
      an increase of tear film stability. The total tear production did not change
      significantly. The moistening effect of Corneregel and low-viscosity artificial
      tears together with intensive regeneration of corneal epithelium enables
      structural recovery of the epithelial membrane and considerable improvement of
      the anterior corneal stroma. CONCLUSION: At the first stage of corneoprotective
      treatment it is appropriate to use preservative-free artificial tears of low and
      high viscosity. If the effect of tear substitutive therapy is unsatisfactory it
      is recommended to prescribe Corneregel and Solcoseryl. The regimen is to be
      adjusted individually.

PMID- 24864505
TI  - [Lattice degeneration of the retina].
AB  - Lattice degeneration of the retina is a clinically important type of peripheral
      retinal dystrophies due to its participation in the pathogenesis of
      rhegmatogenous retinal detachment. In spite of extensive epidemiological,
      morphological, and clinical data, the question on causes of this particular type
      of retinal dystrophies currently remains debatable. Existing hypotheses on
      pathogenesis of retinal structural changes in lattice degeneration explain it to
      a certain extent. In clinical ophthalmology it is necessary to pay close
      attention to this kind of degenerations and distinguish between cases requiring
      preventive treatment and those requiring monitoring.

PMID- 24864504
TI  - [Stargardt's disease and abiotrophy of Franceschetti (fundus flavimaculatus):
      pathogenetic, clinical, and molecular genetic characteristics].
AB  - The article presents a review of literature on Stargardt's disease and abiotrophy
      of Franceschetti. Etiopathogenetic, clinical and molecular genetic
      characteristics are covered. Clinical and genetic classifications of the diseases
      are provided.

PMID- 24864506
TI  - [Diabetic retinopathy in patients with type 1 diabetes mellitus].
AB  - The paper presents an up-to-date review of scientific data. Diabetes mellitus
      (DM), due to its epidemic prevalence and high occurrence of associated
      disability, is now one of the priority medical and social problems.
      Incapacitating manifestations of diabetes include visual impairment. Thus,
      diabetic retinopathy (DR), a late nonspecific vascular complication of DM, is the
      leading cause of blindness in the working-age population. The basic principle of
      DR treatment is optimal compensation of diabetes and concomitant conditions, such
      as arterial hypertension, nephropathy, and hyperlipidemia. Tight glycemic control
      is the main method for preventing and slowing the progression of preproliferative
      DR to later stages. Currently, the optimal and the most promising method of
      insulin injection to diabetes patients is insulin pump, as it enables accurate
      imitation of physiological secretion of insulin, provides the possibility of
      tight glycemic control, considerably decreases the risk for acute and late
      complications of diabetes, etc.

PMID- 24864507
TI  - [Pathogenesis of retinal vein occlusions].
AB  - Retinal vein occlusion (RVO) is a multifactorial disease and its pathogenesis is
      still not fully understood. Mechanical, hemodynamic, rheological, coagulation,
      biochemical, and immunological factors are involved. Two currently prevalent
      theories of RVO pathogenesis are the mechanical theory and the "coagulopathic"
      theory. The latter implies an imbalance between thrombogenic factors and
      antithrombogenic protection. According to some authors, endothelial dysfunction
      plays a large part in thrombosis development, neoangiogenesis, vascular
      remodeling, intravascular activation of platelets and leucocytes. In recent
      studies increasing emphasis is being placed on investigation of immune-mediated
      mechanisms of vein occlusions. RVO can also be associated with combined hypoxic
      and free radical tissue damage.

PMID- 24864508
TI  - [Oxygen therapy in acute myocardial infarction--100 years of confusion].

PMID- 24864509
TI  - [Colleagues! Time to take advantage of future opportunities!].

PMID- 24864510
TI  - [CORAL does not change the treatment of atherosclerotic renal artery stenosis.
      However, the study reinforces the requirement for patient selection prior to
      balloon dilatation].

PMID- 24864511
TI  - [Acute pulmonary embolism with hemodynamic compromise. Management and treatment].

PMID- 24864512
TI  - [Inhaled steroids may cause secondary adrenocortical deficiency. Adult asthmatics
      can also be affected--not just children].

PMID- 24864513
TI  - [Quality work in acute hip fracture could limit renal involvement. Revised care
      program reduced the incidence from 23 to 4 percent].

PMID- 24864514
TI  - [New guidelines for diagnosis and management of stable angina pectoris.
      Recommendations from the European Society of Cardiology].

PMID- 24864515
TI  - [Radical prostatectomy evaluated. 18 year follow up of Swedish randomized
      multicenter study].

PMID- 24864516
TI  - [Occupational health services should clean up the mess "health checks"].

PMID- 24864517
TI  - [Better medical certificates with occupational therapists].

PMID- 24864518
TI  - [Examination harmful for the hearing].

PMID- 24864519
TI  - [The reunion. Medical ideals to remember after 50 years in the profession].

PMID- 24864520
TI  - Hereditary gingival fibromatosis--review of the literature.

PMID- 24864521
TI  - Find the "bright spots".

PMID- 24864522
TI  - As good as it gets? Managing risks of cardiovascular disease in California's top
      performing physician organizations.
AB  - BACKGROUND: The California Right Care Initiative (RCI) accelerates the adoption
      of evidence-based guidelines and improved care management practices for
      conditions for which the gap between science and practice is significant,
      resulting in preventable disability and death. METHODS: Medical directors and
      quality improvement leaders from 11 of the 12 physician organizations that met
      the 2010 national 90th percentile performance benchmarks for control of
      hyperlipidemia and glycated hemoglobin in 2011 were interviewed in 2012.
      Interviews, as well as surveys, assessed performance reporting and feedback to
      individual physicians; medication management protocols; team-based care
      management; primary care team huddles; coordination of care between primary care
      clinicians and specialists; implementation of shared medical appointments; and
      telephone visits for high-risk patients. RESULTS: All but 1 of 11 organizations
      implemented electronic health records. Electronic information exchange between
      primary care physicians and specialists, however, was uncommon. Few organizations
      routinely used interdisciplinary team approaches, shared medical appointments, or
      telephonic strategies for managing cardiovascular risks among patients.
      Implementation barriers included physicians' resistance to change, limited
      resources and reimbursement for team approaches, and limited organizational
      capacity for change. Implementation facilitators included routine use of reliable
      data to guide improvement, leadership facilitation of change, physician buy-in,
      health information technology use, and financial incentives. CONCLUSION: To
      accelerate improvements in managing cardiovascular risks, physician organizations
      may need to implement strategies involving extensive practice reorganization and
      work flow redesign.

PMID- 24864523
TI  - Programs for promoting professionalism: questions to guide next steps.

PMID- 24864524
TI  - Development of a professionalism committee approach to address unprofessional
      medical staff behavior at an academic medical center.
AB  - BACKGROUND: The Joint Commission Leadership standard on the need to create and
      maintain a culture of safety and quality and to develop a code of conduct was
      based on the rationale that unprofessional behavior undermines a culture of
      safety and can thereby be harmful to patient care. Few reports have described
      effective and successful approaches to defining and managing unprofessional
      behavior. The Professionalism Committee (PC)-based approach at the University of
      Pennsylvania Health System (UPHS) may serve as a model for other hospitals and
      health systems. METHODS: Each of the three large teaching hospitals within UPHS
      has a PC that reports to its respective Medical Executive Committee. The PCs
      serve as a resource for department chairs and hospital administrators to address
      unprofessional behavior among faculty. Key features of the PC include the PC
      chair as the first point of contact and the integration of psychiatry into the
      model by virtue of the Professionalism Committee chair's training and expertise
      in psychiatry. RESULTS: In the 2009 calendar year, the PC chair received contacts
      concerning behavior of only 2 physicians, which increased to 42 physicians in
      2011 and 39 in 2012. Contacts involved referrals, management consults, interview
      screening, and the need for general advice. Of 79 resolved cases, 30 involved
      interpersonal issues, and 2 were associated with poor clinical outcomes.
      CONCLUSION: One key feature of the UPHS approach is early identification of the
      role of behavioral health issues in unprofessional behavior (as opposed to
      physical, cognitive, or systems issues) by virtue of the PC chair's professional
      training and expertise. Although aspects of the UPHS experience may not be
      generalizable, the PC structure and approach are replicable.

PMID- 24864525
TI  - Instituting a culture of professionalism: the establishment of a center for
      professionalism and peer support.
AB  - BACKGROUND: There is growing recognition that an environment in which
      professionalism is not embraced, or where expectations of acceptable behaviors
      are not clear and enforced, can result in medical errors, adverse events, and
      unsafe work conditions. METHODS: The Center for Professionalism and Peer Support
      (CPPS) was created in 2008 at Brigham and Women's Hospital (BWH), Boston, to
      educate the hospital community regarding professionalism and manage
      unprofessional behavior. CPPS includes the professionalism initiative, a
      disclosure and apology process, peer and defendant support programs, and wellness
      programs. Leadership support, establishing behavioral expectations and
      assessments, emphasizing communication engagement and skills training, and
      creating a process for intake of professionalism concerns were all critical in
      developing and implementing an effective professionalism program. The process for
      assessing and responding to concerns includes management of professionalism
      concerns, an assessment process, and remediation and monitoring. RESULTS: Since
      2005, thousands of physicians, scientists, nurse practitioners, and physician
      assistants have been trained in educational programs to support the
      identification, prevention, and management of unprofessional behavior. For
      January 1, 2010, through June 30, 2013, concerns were raised regarding 201
      physicians/scientists and 8 health care teams. CONCLUSIONS: The results suggest
      that mandatory education sessions on professional development are successful in
      engaging physicians and scientists in discussing and participating in an enhanced
      professionalism culture, and that the processes for responding to professionalism
      concerns have been able to address, and most often alter, repetitive
      unprofessional behavior in a substantive and beneficial manner.

PMID- 24864526
TI  - Improving the performance of nutrition screening through a series of quality
      improvement initiatives.
AB  - BACKGROUND: Nutrition screening identifies patients at risk of malnutrition to
      facilitate early nutritional intervention, yet incompletion and error rates of
      30%-90% have been reported for commonly used screening tools. The effect of a
      series of quality improvement initiatives in improving the referral process and
      the overall performance of the 3-Minute Nutrition Screening (3-MinNS) tool was
      assessed for patients at National University Hospital (Singapore) at risk for
      malnutrition. METHODS: Annual audits were carried out from 2008 through 2013 on
      4,467 patients. Performance gaps were identified and addressed through
      interventions, including (1) implementing a nutrition screening protocol, (2)
      nutrition screening training, (3) nurse empowerment for online dietetics referral
      of at-risk cases, (4) a closed-loop feedback system, and (5) removing a component
      of 3-MinNS that caused the most errors without compromising its sensitivity and
      specificity. RESULTS: Nutrition screening error rates were 33% and 31%, with 5%
      and 8% blank or missing forms, in 2008 and 2009, respectively. For patients at
      risk of malnutrition, referral to dietetics took up to 7.5 days, with 10% not
      referred at all. After the interventions, nonreferrals decreased to 7% (2010), 4%
      (2011), and 3% (2012 and 2013), and the mean turnaround time from screening to
      referral was reduced significantly from 4.3 +/- 1.8 days to 0.3 +/- 0.4 days (p <
      .001). Error rates were reduced to 25% (2010), 15% (2011), 7% (2012), and 5%
      (2013), and the percentage of blank or missing forms was reduced to and remained
      at 1%. CONCLUSION: Quality improvement initiatives were effective in reducing the
      incompletion and error rates of nutrition screening and led to sustainable
      improvements in the referral process of patients at nutritional risk.

PMID- 24864527
TI  - Physician attitudes toward family-activated medical emergency teams for
      hospitalized children.

PMID- 24864528
TI  - Hospital payment reform for England's NHS.

PMID- 24864529
TI  - Blood pressure control still short of standards.

PMID- 24864530
TI  - Do health plans have a role in limiting antibiotic resistance?

PMID- 24864531
TI  - Medicare's Part D fiasco triggers anger from all sides.

PMID- 24864532
TI  - Health plans innovate to remain relevant.

PMID- 24864533
TI  - Biosimilars take center stage.

PMID- 24864535
TI  - Provider-administered drugs move to specialty pharmacy benefit.

PMID- 24864536
TI  - Old drug in new package promises to calm the agitated.

PMID- 24864537
TI  - 2025: many more elderly, many more specialists.

PMID- 24864538
TI  - I tried to tell you.

PMID- 24864539
TI  - An interview with the President-Elect, Dr. Nelson P. Daly.

PMID- 24864540
TI  - A successful five years.

PMID- 24864541
TI  - Update on office inspections and online license renewals.

PMID- 24864542
TI  - 'Confirmation bias' prevents reconsideration of cannabis.

PMID- 24864543
TI  - Hot topics for St. Louis: the Behavioral Healthcare Leadership Summit.

PMID- 24864544
TI  - ValueOptions names top specialty programs to new 'signature network'.

PMID- 24864545
TI  - The future of behavioral health: under construction.

PMID- 24864547
TI  - Insights into defusing violence, resolving crises.

PMID- 24864546
TI  - Integration demands highest standard of care.

PMID- 24864548
TI  - Untreated mental disorders, unchecked guns.

PMID- 24864549
TI  - The ACA and behavioral health: a look ahead.

PMID- 24864550
TI  - Share with the community, and they will share with you.

PMID- 24864551
TI  - Testing is 'the technology of addiction'.

PMID- 24864552
TI  - Technology disruption: 'it's not always this crazy'.

PMID- 24864553
TI  - Surrounding recovery with nature.

PMID- 24864554
TI  - Cultural obstacles to aging with grace.

PMID- 24864555
TI  - All the stars have aligned for Lincoln Square.

PMID- 24864556
TI  - QAPI: A foundation for successful caregiving.

PMID- 24864557
TI  - Companionship exemption: know the rules.

PMID- 24864558
TI  - Volunteer programs take a quantum leap.

PMID- 24864559
TI  - Five tips for successful tech adoption.

PMID- 24864560
TI  - [Mental Health Atlas 2011 (WHO)].

PMID- 24864561
TI  - [An intervention to promote team-based care: two focus groups--what promotes team
      based care?].
AB  - There has recently been interest in new models of care delivery that promote a
      team-based approach in psychiatric care. The aim of the study was to clarify the
      way in which to promote a team-based approach in psychiatric hospitals. Two focus
      groups were held to collect data from psychiatric hospital nurses who underwent
      the intervention to improve collaborative behavior. The results indicated the
      effectiveness of the program to encourage different professionals to meet and
      interact in learning to improve collaborative practice. We commented on the
      importance of conflict management and system change. The results are discussed in
      relation to previous research and practical implications.

PMID- 24864562
TI  - [The revised system of hospitalization for medical care and protection].
AB  - The Act to Partially Amend the Act on Mental Health and Welfare for the Mentally
      Disabled was passed on June 13, 2013. Major amendments regarding hospitalization
      for medical care and protection include the points listed below. The guardianship
      system will be abolished. Consent by a guardian will no longer be required in the
      case of hospitalization for medical care and protection. In the case of
      hospitalization for medical care and protection, the administrators of the
      psychiatric hospital are required to obtain the consent of one of the following
      persons: spouse, person with parental authority, person responsible for support,
      legal custodian, or curator. If no qualified person is available, consent must be
      obtained from the mayor, etc. of the municipality. The following three
      obligations are imposed on psychiatric hospital administrators. (1) Assignment of
      a person, such as a psychiatric social worker, to provide guidance and counseling
      to patients hospitalized for medical care and protection regarding their
      postdischarge living environment. (2) Collaboration with community support
      entities that consult with and provide information as necessary to the person
      hospitalized, their spouse, a person with parental authority, a person
      responsible for support, or their legal custodian or curator. (3) Organizational
      improvements to promote hospital discharge. With regard to requests for
      discharge, the revised law stipulates that, in addition to the person
      hospitalized with a mental disorder, others who may file a request for discharge
      with the psychiatric review board include: the person's spouse, a person with
      parental authority, a person responsible for support, or their legal custodian or
      curator. If none of the above persons are available, or if none of them are able
      to express their wishes, the mayor, etc. of the municipality having jurisdiction
      over the place of residence of the person hospitalized may request a discharge.
      In order to promote transition to life in the community by persons with mental
      disorders, efforts will be made to enhance psychiatric care for them, with
      guidelines to be developed to ensure the provision of medical care to persons
      with mental disorders. The revised law clarifies that members of psychiatric
      review boards shall be "persons with expert knowledge and experience pertaining
      to the health and/or welfare of persons with mental disorders." Provision is made
      for a review of conditions related to implementation of the revised law
      approximately three years after it takes effect, with measures to be taken as
      necessary based on results of the review. The main focus of this presentation
      will be the revisions to the system of hospitalization for medical care and
      protection, and the deletion of provisions relating to the system of
      guardianship.

PMID- 24864563
TI  - [Inpatient advocacy under the new system of involuntary hospitalization].
AB  - I considered both procedural and substantive requirements for patient advocacy in
      the context of involuntary hospitalization, and reviewed the revised Act on
      Mental Health and Welfare for the Mentally Disabled. I concluded that the revised
      act does not satisfy either procedural or substantive requirements for the
      advocacy of patients. The revised act stipulates that it be reviewed after three
      years. Along with carefully monitoring implementation of the new law, we must
      also create systems for reviewing the introduction of advocators, as well as
      enhancements to psychiatric review boards.

PMID- 24864564
TI  - [Advocacy and early discharge under the new system of hospitalization for medical
      care and protection].
AB  - The Act on Mental Health and Welfare for the Mentally Disabled was partially
      amended during the 183rd ordinary session of the Diet, on June 13, 2013. The
      revision abolished the system of guardianship that had long imposed conflicting
      roles on families of people with mental disorders. Various issues and concerns
      remain, however, including the requirement that consent for hospitalization be
      provided by a family member. Many people who need involuntary hospitalization
      find themselves in situations where it is difficult to continue living in the
      community. At the time of hospital admission, along with a medical examination,
      it is necessary to assess the patient's support system in the community and
      ascertain whether "hospitalization for medical care and protection" is, in fact,
      the only option. When hospitalization for medical care and protection is
      determined to be unavoidable, treatment and planning focused on early discharge
      and the patient's return to life in the community should be initiated immediately
      after hospitalization. Actual patient outcomes clearly indicate that early
      discharge is often the result when medical institutions collaborate and network
      with multidisciplinary teams and community support workers immediately after
      hospitalization. It is hoped that the amended law will have a practical impact
      that will result in similar outcomes throughout the nation in the future. At the
      same' time, it is crucial to expand staffing in medical institutions, foster a
      culture of team treatment, and promote the creation of better community mental
      health systems that include housing, social resources, and family support.

PMID- 24864565
TI  - [A criticial view of involuntary hospitalization and patient protection after
      abolishment of the system of guardianship under the 2011 revision to the act on
      mental health and welfare for the mentally disabled].
AB  - The current system of guardianship is to be abolished under the Revised Mental
      Health and Welfare Act. Aging patients and changing family structures highlight
      the need for public services based on parens patriae. The proposed new system of
      involuntary hospitalization continues to require family member consent, as in
      civil contracts, and legal authority remains ambiguous, with the government
      neglecting its responsibility to guarantee inpatient treatment and community
      services. Many long-term patients are scheduled to be cared for in hospitals more
      cheaply than is currently the case, and community services are assumed to be
      funded through those savings, but such services are nothing more than accessories
      with extra beds. In the long term, it is necessary to consider comprehensive
      legislation on compulsory treatment and restrictions to freedom related to both
      physical and mental disorders in the context of the Convention on the Rights of
      Persons with Disabilities.

PMID- 24864566
TI  - [Mind and brain "Kasane-egaki (Oomori, S.)"].
AB  - A mind-brain problem might be explainable by the concept "Kasane-egaki (Oomori,
      1994)". Kasane-egaki of the mind and brain is crucial and meaningful in medical
      treatment. For Kasane-egaki, it is important to note that the mind (psychiatric
      symptoms) must be translated into an expression which could be connected with the
      brain function, and vice versa As a case of Kasane-egaki, a patient with left
      frontal infarction showing mild obsessive-compulsive-like symptoms is introduced.
      However, there are two situations in which Kasane-egaki of the mind and brain
      cannot be applied: visual agnosia and auditory hallucination of schizophrenia The
      author discusses visual experiences of patients with associative visual agnosia,
      and the relation between auditory hallucination of schizophrenia and activation
      of the temporal lobe from the viewpoint of language function.

PMID- 24864568
TI  - [Future of the Board Certification System for Medical Specialties in Japan].

PMID- 24864567
TI  - [Adverse events of psychotropic drugs].
AB  - The authors discuss adverse events which are often missed but clinicians should
      pay attention to in order to preserve patients'quality of life(QOL). Among mood
      stabilizers, lithium may cause a urinary volume increase, hyperparathyroidism,
      and serum calcium elevation; sodium valproate possibly increases androgenic
      hormone levels and the risk of polycystic ovary syndrome (PCOS) as well as
      hypothyroidism. Moreover, in addition to teratogenesis, it has been reported that
      fetal exposure to a higher dose of valproate is associated with a lower
      intelligence quotient and higher incidence of autism spectrum disorders in
      children. Antidepressants with a higher affinity for serotonin transporters might
      induce gastrointestinal bleeding, and some antidepressants cause sexual
      dysfunction more frequently than others. Activation syndrome is still a key side
      effect which should be noted. Regarding the adverse events of antipsychotics,
      subjective side effects unpleasant to patients such as dysphoria and a lower
      subjective well-being should not be overlooked. We clinicians have to cope with
      adverse events worsening the QOL of patients with psychiatric disorders and,
      therefore, we need to adopt appropriate counter-measures.

PMID- 24864569
TI  - [Anesthesia and perioperative management for highly invasive major surgery:
      preface and comments].
AB  - Despite a drastic decline in anesthesia-related morbidity and mortality,
      perioperative mortality remains still high with an overall rate around 1 to 2%.
      To improve postsurgical outcomes ultimately, anesthesiologists should move
      forward to take more responsibility in the perioperative management of patients.
      In this issue, we selected several types of highly invasive surgical procedures
      and reviewed anesthesia and perioperative management for the patients undergoing
      these surgeries. Team approach by various professionals may facilitate organizing
      pre-, intra-, and postoperative care.

PMID- 24864570
TI  - [Perioperative management for esophagectomy].
AB  - Esophagetomy is considered as one of the most invasive surgical procedures.
      Despite marked advances in surgical techniques, anesthetic management and
      intensive care, the morbidity and mortality remain still high compared with the
      other types of surgery. Excessive inflammatory response after surgery induces
      over-production of inflammatory cytokines, leading to the development of vital
      organ failures. Anesthesiologists should pay much attention to perioperative
      management of patients undergoing esophagectomy since they are potentially at
      high risks of respiratory and cardiovascular complications caused by excessive
      stress with cervical, thoracic and abdominal procedures. During surgery, many
      interventions such as effective epidural anesthesia, restrictive fluid
      management, lung protective strategy, maintenance of hemodynamic stability and
      steroid therapy should be considered. Perioperative respiratory management
      including early extubation, intensive physical therapy, early mobilization and
      rehabilitation with enteral nutrition are all important to prevent postoperative
      complications and to shorten the length of hospital stay. However, some patients
      need longer-term mechanical ventilation due to preoperative respiratory
      dysfunction and reduced cough reflex by surgical manipulations. A multimodal
      treatment is warranted to improve the outcomes after esophagectomy.

PMID- 24864571
TI  - [OPCAB].
AB  - Off-pump coronary artery bypass grafting (OPCAB) has some advantages in reduction
      of postoperative complications including systematic inflammatory response,
      myocardial injury, renal injury and cerebral injury, compared to on-pump coronary
      artery bypass grafting. It is important to reduce myocardial oxygen consumption
      during anesthesia for OPCAB. The anesthesiologists should collaborate with the
      cardiac surgeons and plan the best perioperative strategy for rapid recovery. The
      anesthesiologists should pay attention to hemodynamic instability and myocardial
      ischemia during anastomosis. Fast-track anesthesia offers many benefits which
      lead to earlier ambulation, earlier discharge and earlier rehabilitation. Further
      fast-track anesthesia including extubation after OPCAB in the operating room is
      needed, but can only be performed in selected patients.

PMID- 24864572
TI  - [Pneumonectomy and lobectomy].
AB  - Thoracic surgery developed remarkably in tandem with anesthetic management and
      post-operative intensive care since 1990. The innovations in these fields include
      wide spread use of one-lung ventilation, advances in clarification of
      pathophysiology of postoperative acute lung injury as well as its treatment,
      initiation of lung protective ventilation strategy, advancement of chest
      physiotherapy, and wide use of non-invasive ventilation in the last two decades.
      Current guidelines support strongly the use of lower tidal volume in patients
      with acute lung injury and acute respiratory distress syndrome. Under the
      influence of this new lung protective ventilation strategy, perioperative
      managements such as setting of tidal volume changed drastically in nearly ten
      years. The purpose of this article is to review the innovations and the
      transitions in anesthetic management and post-operative intensive care in
      thoracic surgery, and to propose up-to-date peri-operative respiratory strategies
      for patients undergoing thoracic surgery, especially pneumonectomy.

PMID- 24864573
TI  - [Spinal instrumentation and spinal fusion surgery].
AB  - In this article, we review the potential complications of spinal instrumentation
      discussing various types of postoperative complications. Surgical implants in
      spinal surgeries are used to stabilize the spine, replace the defective parts and
      maintain anatomic reduction. Internal spinal instrumentation has undergone
      considerable advances during the last century. However, the spinal
      instrumentation is an invasive surgery, and postoperative complications occur
      frequently after the spinal deformity surgery. Elderly patients, who may have
      many histories of medical complications and osteoporosis, have a higher
      complication rate. Pulmonary complications are the most common life-threatening
      postoperative complications. The acute onset of neurologic symptoms in the
      immediate postoperative period should arouse clinical suspicion about the
      possible formation of a hematoma. Such occurrences require urgent surgical
      decompression. Better recognition of postoperative risk factors and early
      detection of urgent signs may lead to decrease complication rates and may improve
      outcomes. Although the latest monitoring system is very useful we should
      recognize that the observation of the patients by the five senses is the most
      important way to detect the postoperative medical complications early.

PMID- 24864574
TI  - [Perioperative management of patients for living-donor liver transplantation].
AB  - Living-donor liver transplantation has become a standard and effective treatment
      for end stage liver disease patients. As a result of remarkable progress in
      immunosuppressive drugs, surgical device, anesthetics, and appropriate
      perioperative management, liver-transplanted patients may experience fewer
      complications, shorter length of ICU stay, and a better overall outcome. However,
      unexpected perioperative complications remain substantial. Therefore, we take
      care in several points in perioperative period. First, we should appropriately
      evaluate general preoperative conditions, such as coagulopathy, ascites,
      respiratory and renal function. Second, we need to maintain hemodynamic
      stabilization, electrolyte balance, correction of coagulopathy and prevention of
      portal hypertention during operation. And third, in postoperative period we
      should perform strict monitoring and focus on infection prophylaxis, early
      weaning from mechanical ventilation, appropriate administration of fluid and
      transfusion, maintaining renal function and preservation of graft function.
      Appropriate knowledge and understanding of perioperative management in liver
      transplantation are required to improve patient's outcome. Furthermore, it is
      important for performing liver transplantation to boost mutual understanding and
      trust in the medical team including health-care providers.

PMID- 24864575
TI  - [Perioperative management of skull base tumor surgery].
AB  - In this chapter, vital points in perioperative management of skull base tumor
      (SBT) surgery are described. Not only surgical techniques and devices but also
      peri-operative management have been greatly improved in a relatively short period
      of time, resulting in many additional indications for more complex procedures.
      Anesthesiologists have therefore assumed more responsibility for the
      perioperative management of patients. We begin with an introduction of newly
      developed surgical approaches and a review of major perioperative complications
      for each approach. Next we describe intraoperative electrophysiological
      monitoring (IOEM) methods for neuronal protection. Neuronal damage can be caused
      by maneuvers for obtaining better views of surgical fields, such as compression
      of juxtaposed tissues and clamping of major arteries. Thus, IOEM should be used
      for not only structures in the surgical field but also surrounding structures
      that are exposed to risk of damage. Finally, we describe intraoperative
      anesthetic management and postoperative intensive care. Some of the methods that
      were once considered to be neuroprotective have been denied by results of recent
      studies. Anesthesiologists should therefore update their knowledge of
      perioperative management for SBT surgery to promote patient safety.

PMID- 24864576
TI  - [One-lung ventilation using dexmedetomidine in an emphysema patient with
      pneumothorax due to metastatic lung cancer].
AB  - We report a case of double-lumen tube intubation and intraoperative one-lung
      ventilation under spontaneous breathing with continuous dexmedetomidine
      administration. A 61-year-old man developed pneumothorax due to multiple
      metastatic cancer, had multiple bilateral bullae, and underwent bullae resection
      under general anesthesia. An epidural catheter was placed at T8-9. Under
      dexmedetomidine sedation and regional anesthesia with lidocaine, a double-lumen
      tube was inserted with a Macintosh laryngoscope. The patient was under one-lung
      ventilation with spontaneous breathing during the operation. There were no
      complications from one-lung ventilation and the patient was extubated in the
      operating room. One-lung ventilation, which preserves spontaneous breathing,
      under dexmedetomidine sedation is considered effective for preventing barotrauma
      in patients with multiple metastatic cancer.

PMID- 24864577
TI  - [Successful intubation in a difficult case using an Ambu Laryngeal Mask Angle
      Type-i, and the ability to pass a gastric tube behind the laryngeal mask].
AB  - A 71-year-old male was scheduled for a laparoscopic cholecystectomy. The plan was
      to intubate him using direct laryngoscopy. After induction of anesthesia and
      analgesia direct laryngoscopy was performed but it was difficult to get a good
      view of epiglottis, and at 2nd attempt there was laryngeal edema, which made the
      procedure more difficult. The patient was then ventilated with a facemask and it
      was decided to intubate him with an Ambu Laryngeal Mask Angle Type-i (Aura-i) and
      a bronchofiberscope. The procedure worked, and the patient was successfully
      intubated. We did not want to remove the Aura-i due to concerns about losing the
      airway. Therefore, we decided to place the gastric tube with the Aura-i still
      inserted. Therefore the cuff of the Aura-i was deflated and we were able to
      easily pass a gastric tube behind the Aura-i type easily. After the operation,
      the patient was extubated from the trachea with the Aura-i still in place. When
      sufficient respiration returned, the Aura-i was removed. There was no bleeding in
      the mouth after removal of the Aura-i.

PMID- 24864578
TI  - [Airway obstruction during attempts at fiberoptic intubation in an awake
      patient].
AB  - A 67-year-old woman with rheumatoid arthritis was scheduled for lumbar anterior
      fusion (L5-S1). The patient had undergone several major operations on the
      cervical to the lumbar spine. Cervical spine movement was severely restricted,
      the mouth opening was limited (inter-incisor distance 3 cm), and the jaw was
      small (thyro-mental distance 2 cm). During previous anesthesia tracheal
      intubation was always difficult. Fiberoptic nasotracheal intubation while the
      patient was sedated was planned. After bilateral superior laryngeal nerves had
      been blocked using 1% lidocaine, sedation was achieved using midazolam 1.4 mg and
      fentanyl 0.025 mg. Fiberscopy showed an edematous larynx, due probably to
      rheumatoid arthritis and to a long-term steroid therapy. It was possible to
      insert a fiberscope into the trachea, but it was difficult to pass a reinforced
      tube (6.0 mmID) and the procedure led to airway obstruction with a decreased
      arterial hemoglobin oxygen saturation. At the second attempt at fiberoptic
      intubation a rapidly swollen larynx was observed and awake intubation was
      abandoned. Fiberoptic intubation could be perfomed after induction of general
      anesthesia. This case indicates that, although awake fiberoptic intubation is
      regarded as the safest and the most reliable method, this may also be associated
      with severe airway obstruction.

PMID- 24864579
TI  - [A case of a laryngeal granuloma detached by tracheal intubation].
AB  - Unique risks are involved in tracheal intubation with a laryngeal granuloma
      lodged in the subglottis and special precautions must be taken to manage such
      intubation. Reported is a case of laryngeal granuloma, which was detached from
      the larynx by the intubation. We discuss the management of tracheal intubation in
      the aforementioned case.

PMID- 24864580
TI  - [Successful perioperative use of noninvasive positive pressure ventilation in a
      pregnant woman with acute pulmonary edema].
AB  - A 32-year-old woman (148 cm, 59 kg, gravida 2, para 2) with quadruplet pregnancy
      was admitted to our hospital for the threatened preterm labor at 23 weeks and 2
      days of gestation. She was treated with ritodrine, magnesium sulfate and
      nifedipine to maintain tocolysis. Betamethasone was administered to accelerate
      fetal lung maturity. After ritodrine dose was increased at 23 weeks and 5 days of
      gestation, she developed dyspnea with desaturation. Acute pulmonary edema was
      revealed on chest X-ray. The decision was made to proceed with emergency cesarean
      delivery. On arrival at the operating room, the blood pressure was 123/53 mmHg,
      heart rate 111 beats x min(-1), and oxygen saturation (SpO2) 84% with
      supplemental oxygen 15 l x min(-1) via a reserved face mask. Noninvasive positive
      pressure ventilation (NPPV) was initiated with S/T mode (FIO2 1.0, inspiratory
      positive airway pressure 10 cmH2O, expiratory positive airway pressure 6 cmH2O).
      The dyspnea was improved with her SpO2 100%. Spinal anesthesia was performed at L
      34 using 2.5 ml of 0.5% bupivacaine and 100 microg morphine. Throughout the
      operation (operation time 44 minutes), she did not develop dyspnea under NPPV.
      NPPV was discontinued after the operation. Her SpO2 declined, and pulmonary edema
      on chest X-ray was exacerbated. She was transferred to the intensive care unit
      and NPPV was continued for 22 hours after the operation. She was discharged from
      the intensive care unit on the next day and was discharged from the hospital on
      the 6th postoperative day.

PMID- 24864581
TI  - [Combined use of continuous epidural anesthesia nand transversus abdominis plane
      block for postoperative management of cesarean delivery in a patient whose
      previous cesarean deliveries were not properly controlled].
AB  - We report the successful combined use of continuous epidural anesthesia and
      transversus abdominis plane block for the management of postoperative pain
      following a cesarean delivery in a patient whose paralysis and pain were not well
      controlled after two previous cesarean deliveries. A 28-year-old female patient
      with no remarkable medical history was scheduled to undergo cesarean delivery at
      38 weeks and 3 days of pregnancy. She had undergone cesarean deliveries twice
      previously, at 23 and 25 years of age. Both of these procedures were concluded
      using combined spinal-epidural anesthesia. However, in both procedures, the
      continuous epidural catheter could not be removed within 12 hours because of
      paralysis of the right leg and sharp pain. Therefore, during the third operation,
      the concentration of the continuous epidural anesthesia infusion was decreased to
      prevent complications, and a transversus abdominis plane block was added. The
      patient experienced no postoperative pain and fewer complications. We think that
      the combined use of these blocks provided good postoperative pain control with
      fewer complications.

PMID- 24864582
TI  - [Inferior vena cava thrombosis reaching the right atrium after removal of the
      central venous catheter at femoral vein in a patient with diabetic ketoacidosis].
AB  - A 19-year-old male was admitted with diabetic ketoacidosis. A central venous
      catheter for fluid loading and insulin administration was inserted from the right
      femoral vein. The catheter was placed for 4days and was removal. Three days after
      removal thrombus was pointed out with echocardiography. Cardiac ultrasound
      revealed floating thrombi in the right atrium. Venography demonstrated a large
      thrombus from the right femoral vein to the end of the inferior vena cava.
      Emergency surgery was performed. A tubular thrombus was trapped from the inferior
      vena cava departure at the right atrium under cardiopulmonary bypass. The surgeon
      also implanted an inferior vena caval filter. The patient was weaned from
      ventilator assist next day and was discharged from the hospital 13 days later.
      This case suggests that deep vein thrombosis should be checked in diabetic
      ketoacidosis even after removal of a central venous catheter implanted at the
      femoral vein.

PMID- 24864584
TI  - [A patient with congenital antithrombin III deficiency who underwent laparoscopic
      renal resection].
AB  - A 66-year-old man with congenital antithrombin III (ATIII) deficiency was
      scheduled to undergo laparoscopic renal resection. On admission the plasma ATIII
      activity was as low as 56%. After giving ATIII intravenously, the plasma ATIII
      activity increased to 103% on the day of surgery. It is usually difficult to
      monitor ATIII during surgery. Instead, we measured activated clotting times
      (ACTs). The ACT before operation was 178 seconds. During the operation, the ACT
      dropped to 81 seconds. We administered 3,000 units of heparin, and the ACT
      increased to 182 seconds. After surgery, the plasma ATIII activity was 68%. We
      managed the ACT activity to a target value of 100% postoperatively, until the
      patient was switched from heparin to oral warfarin. He was discharged without
      complications 10 days after surgery. In this patient, the ACT decreased during
      the operation, as did the ATIII activity. Although the half-life of the ATIII
      preparation was 3 days, it appeared that the ATIII activity, which was high
      preoperatively, decreased during the operation. Coagulation abnormalities could
      be managed quickly by measuring ACT. Our results suggest that the measurement of
      ACT is an effective technique for the intraoperative monitoring of patients with
      congenital ATIII deficiency.

PMID- 24864583
TI  - [A case of dexmedetomidine administration for slight end-stage sedation in a
      patient with sudden continuous bleeding].
AB  - We report a case of sudden fatal bleeding during the treatment of pancreatic
      cancer. The patient underwent palliative treatment for his symptoms with
      hydroxyethyl starch (HES) and continuous dexmedetomidine. He suffered from
      advanced pancreatic cancer, underwent gastrojejunostomy, and was scheduled to
      undergo chemotherapy. He suddenly vomited large amounts of blood and his blood
      pressure fell. Computed tomography revealed a hole in the branch of the arteria
      mesenterica superior that supplies the duodenum; best supportive care was
      selected. The patient suffered from pain associated with low blood pressure
      throughout his body. Infusion of 6% HES and continuous dopamine alleviated the
      pain and normalized his blood pressure. Continuous dexmedetomidine reduced his
      fatigue. He was able to talk comfortably with his family for 72 hours during
      treatment. Subsequently, his level of consciousness deteriorated and we
      administered haloperidol and midazolam for continuous sedation. He died
      painlessly 120 hours later after dexmedetomidine initiation.

PMID- 24864585
TI  - [Loss of anesthesia records during network failure of anesthesia management
      information system: a case of malfunction of backup system].
AB  - We report a case of an accidental loss of anesthesia records through network
      failure of an anesthesia information management system (AIMS). The backup data
      were not kept in the anesthesia workstations or the server during the failure.
      Accordingly, anesthesia records of five patients were lost for one hour. Our AIMS
      has a network redundancy where the server keeps anesthesia monitoring data via
      two pathways: one via the monitoring server to the AIMS server and the other via
      anesthesia workstation to the server. Despite the redundant pathways, transient
      power failures of network switches caused interruptions in both pathways. Our
      case indicates that, to improve the robustness of the AIMS as electronic medical
      records, every network apparatus of AIMS, should be supplied with an
      uninterrupted power supply. Furthermore, each anesthesia workstation should
      function independently as an anesthesia record keeping client when network
      failure occurs.

PMID- 24864586
TI  - [Difference in nitrous oxide-mediated increases in intracuff pressure between two
      tracheal tubes in a simulated pediatric lung model].
AB  - BACKGROUND: The purpose of this study was to compare the nitrous oxide-mediated
      increases in cuff pressure between a tracheal tube with a tapered cuff (Taper) or
      conventional high volume low pressure cuff (HVLP) utilizing a simulated pediatric
      lung model. METHODS: The automated cuff pressures were adjusted to 10, 20, and 30
      cmH2O. The Taper and HVLP were exposed to 80% nitrous oxide and cuff pressure was
      measured 15 and 30 minutes later. RESULTS: The cuff pressure of the Taper was
      significantly lower than that of the HVLP after 15 and 30 minutes, regardless of
      the initial pressure. CONCLUSIONS: These findings suggest that the Taper may be
      more effective than the HVLP in preventing hyperinflation of the tracheal tube
      cuff in response to nitrous oxide exposure in children.

PMID- 24864587
TI  - [Refinement of the simulation-based sedation training course based on sedation
      and analgesia guidelines for non-anesthesiologists by American Society of
      Anesthesiologists].
AB  - We report the refinement of the simulation-based sedation training course (SEDTC)
      hosted by the Japanese Association of Medical Simulation, and the drafting and
      development of an learning goal and instructor course. In basic airway management
      training, we highlighted the importance of the "call for help" and oxygen supply.
      In card-based simulation training sessions, we posted a picture detailing
      recommended amounts of oxygen and the duration of its use. We set the time of
      preplanning of sedation strategy in the simulation-training. Twenty-seven SEDTCs
      were conducted between August 2011 and March 2013 at several locations in Japan.
      A total of 395 medical staffs affiliated with various medical departments
      participated in the courses. SEDTCs may serve as a vehicle to improve the safety
      of sedation and analgesia.

PMID- 24864588
TI  - [Comparison of TaperGuard tube and the Portex Softseal for prevention of vomitus
      leakage in an in vitro simulation airway model].
AB  - BACKGROUND: Microaspiration of vomitus can cause a serious condition known as
      Mendelson's syndrome. The present study used simulated stomach contents and an
      airway model to compare a tracheal tube with a tapered cuff (Taper) to the
      conventional high volume low pressure cuff (HVLP) in their abilities to prevent
      microaspiration. METHODS: The automated cuff pressure was adjusted to 10, 20, and
      30 cmH2O. We poured 5 ml of simulated stomach contents above the cuff in the
      vertically situated airway model and measured the leakage volume after 5 minutes
      as well as 4 hours. RESULTS: After 5 minutes, leakage volume was significantly
      lower for the Taper than for the HVLP at 10 cmH2O, but not for 20 and 30 cmH2O.
      After 4 hours, stomach content leakage was significantly less with the Taper than
      with the HVLP, regardless of cuff pressure (P < 0.05). CONCLUSIONS: We conclude
      that the Taper may be more effective than the conventional HVLP in preventing
      vomitus microaspiration in an airway model simulation.

PMID- 24864589
TI  - [Shift of the i-gel position after chest compression: comparison of fixation
      methods using Durapore tape, Multipore tape, or a fixation strap].
AB  - BACKGROUND: The i-gel (Intersurgical, Wokingham, U.K.) is a newly developed, non
      inflatable supraglottic device characterized by its soft, gel-like, and
      transparent mask made of thermoplastic elastomer. Although i-gel can be useful in
      emergency airway management during chest compression, the instability after
      insertion remains a problem. METHODS: We investigated the effectiveness of three
      fixation methods using a manikin and automated chest compressor. RESULTS: After 5
      minute chest compression, i-gel without fixation was shifted by 0.56 +/- 0.17 cm,
      which was greater than with Durapore tape (0.28 +/- 0.08 cm), Multipore tape
      (0.26 +/- 0.05 cm), or a fixation strap (0.04 +/- 0.05 cm). The shift of the
      position was smaller with strap fixation compared to Durapore or Multipore tape
      fixation. CONCLUSIONS: A fixation strap may be useful in stabilizing the inserted
      position of i-gel during cardiopulmonary resuscitation.

PMID- 24864590
TI  - [The background for governmental accreditation of "anesthesiology" as a specially
      approved medical specialty].

PMID- 24864591
TI  - Preventing transmission of hepatitis C due to unsafe injections should be a
      priority for Pakistan.

PMID- 24864592
TI  - Comparison of efficacy of ondansetron and dexamethasone combination and
      ondansetron alone in preventing postoperative nausea and vomiting after
      laparoscopic cholecystectomy.
AB  - OBJECTIVE: To compare the efficacy of ondansetron alone and combination of
      ondansetron and dexamethasone in preventing post-operative nausea and vomiting in
      patients undergoing laparoscopic cholecystectomy. METHODS: The randomised control
      trial was conducted from April 23 to August 22, 2009, at the Liaquat National
      Hospital, Karachi, and comprised 100 American Society of Anaesthesiology I and II
      patients undergoing laparoscopic cholecystectomy. Half of the subjects comprised
      Group A and received ondansetron alone, while Group B received combination of
      ondansetron and dexamethasone. They were randomised by opaque envelope method.
      Group A received ondansetron 4 mg while Group B received ondansetron 4 mg with
      dexamethasone 8 mg, 1 minute before induction. Post-operatively patients were
      observed for six hours for any episode of nausea or vomiting, or whether the
      patients required any rescue anti emetic. SPSS 19 was used for statistical
      analysis. RESULTS: Patients receiving ondansetron alone showed 14 (28%) with
      incidence of nausea or vomiting while the other group showed 6 (12%). This
      difference was statistically significant (p < 0.046). CONCLUSION: Combination of
      ondansetron and dexamethasone was more efficacious compared to ondansetron alone
      in the prevention of postoperative nausea and vomiting in patients undergoing
      laparoscopic cholecystectomy.

PMID- 24864593
TI  - Frequency of co-existence of dengue and malaria in patients presenting with acute
      febrile illness.
AB  - OBJECTIVE: To find out the frequency of co-existence of malaria and dengue fever
      in patients presenting with acute febrile illness. METHODS: The descriptive cross
      sectional study was conducted at the Military Hospital Rawalpindi from June to
      November 2012. A total of 500 patients with complaint of acute febrile illness
      were selected after applying the inclusion and exclusion criteria. Preliminary
      data was collected on a pretested proforma. Blood samples of patients were tested
      for dengue serology and malaria parasite. Results were entered in respective
      proforma. Co-existence was considered present when a patient had both dengue
      serology and malaria parasite slide positive. SPSS 20 v was used for data
      analysis. RESULT: Of the total, 349 (69.8%) were males and 151 (30.2%) females.
      Dengue serology was positive in 16 (3.2%); 81(16.2%) had malaria parasite slide
      positive; 403 (80.4%) had none of the two findings. Co-existence of both dengue
      and malaria was nil among the whole sample. In males, 67 (13.4%) had malaria,
      while 11 (2.2%) had dengue. In females, 14 (2.8%) had malaria, while 5 (1%)
      suffered from dengue fever. CONCLUSION: Co-existence of dengue and malaria was
      zero per cent in 500 patients visiting Military Hospital Rawalpindi. More studies
      shall be conducted to find out whether the reason of having zero per cent co
      existence is that dengue or/and malaria epidemic did not occur in 2012 or whether
      there are some other factors involved.

PMID- 24864594
TI  - How many times should the uroflowmetry be repeated before making a treatment
      decision in the elderly males?
AB  - OBJECTIVE: To investigate the effect of repeating uroflowmetry test on results of
      patients with or without lower urinary tract symptoms. METHODS: The prospective
      study was conducted at the Department of Urology, Ankara Training and Research
      Hospital, Turkey, from August to December 2012, and comprised 79 consecutive male
      patients with or without infravesical obstruction symptoms. All patients
      underwent uroflowmetry testing thrice on different occasions. The urinary maximum
      flow rate, average flow rate, voided volume (> or = 150 ml), voiding time, flow
      time and time to void values were evaluated. SPSS 16 was used for statistical
      analysis. RESULTS: The overall mean of maximum flow rate was 11.4 +/- 1.69, 12.4
      +/- 1.47 and 13.7 +/- 1.44 ml/sec at the first, second and third repetition
      respectively (p > 0.05). The mean percentage difference in maximum flow was +8%
      higher between the first and second attempt, and +4% higher between the second
      and third attempt. The mean average flow rate, the mean voiding time and the mean
      flow time values were also found to have insignificantly improved. The mean
      voided volumes of the patients were 201 +/- 48, 209 +/- 57 and 248 +/- 61 ml,
      respectively (p > 0.05). The time to void decreased significantly in the second
      and third attempts (p < 0.01). CONCLUSION: Repeating uroflowmetry exhibits a
      minor improvement in maximum and average flow rates, and voided values in men,
      while a significant decrease was noted in time to void.

PMID- 24864595
TI  - Susceptibility of methicillin-resistant Staphylococcus aureus and enterococci to
      teicoplanin in Pakistan: the MRSET study.
AB  - OBJECTIVE: To evaluate the susceptibility pattern of S. aureus and enterococci to
      teicoplanin using an in vitro method. METHODS: Between February and November
      2011, valid bacteriological samples were collected at three hospitals in three
      cities in Pakistan and the organism was isolated. Only samples containing S.
      aureus or enterococci were tested for their sensitivity to teicoplanin and
      various other standard antimicrobials in therapy, using the disc diffusion
      testing by the Kirby-Bauer method. SPSS 18 was used for statistical analysis.
      RESULTS: Of the 401 isolates collected, a majority 293 (59.6%) were methicillin
      sensitive S. aureus, while 136 (33.9%) were methicillin-resistant S. aureus; and
      26 (6.5%) were enterococci. All isolates were sensitive to teicoplanin and
      vancomycin. CONCLUSION: Teicoplanin had the same in vitro sensitivity as
      vancomycin against methicillin-sensitive S. aureus, methicillin-resistant S.
      aureus and enterococci in clinical isolates.

PMID- 24864597
TI  - Measurements of central corneal thickness using two immersion ultrasound
      techniques and optical technique.
AB  - OBJECTIVE: To compare the accuracy of central corneal thickness measurements
      using ultrasound biomicroscopy, Orbscan II tomography and an Artemis-2 very high
      frequency ultrasound scanner. METHODS: The prospective study was conducted at Eye
      World Centre, Riyadh, Saudi Arabia, from September to November 2012. One eye from
      each of 60 normal subjects was analysed. The central corneal thickness was
      measured using ultrasound biomicroscopy, Orbscan II tomography and the Artemis-2
      very high frequency ultrasound scanner. Results were compared using analysis of
      variance, repeated-measures analysis of variance and limits of agreement.
      RESULTS: The mean central corneal thickness was 530.30 +/- 30.75 microm, 548.95
      +/- 30.33 microm and 554.73 +/- 31.97 microm for biomicroscopy, tomography and
      the scanner respectively. The intraobserver repeatability analyses of variance
      were not significant for the three procedures (p = 0.19, 0.23 and 0.41,
      respectively). A significant difference was noted among the three different
      methods (p = 0.0001). However, comparison among instruments revealed no
      significant difference between tomography and the scanner (p > 0.05), yet
      significant differences were noted in biomicroscopy vs. tomography, and
      biomicroscopy vs. the scanner (p < 0.01 and P < 0.001, respectively). The mean
      differences (and upper/lower limits of agreement) for central corneal thickness
      measurements were 18.92 +/- 40.71 (60.90/-98.70); 24.7 +/- 13.13 (1.00/-50.40),
      and -5.80 +/- 38.61 (69.90/-81.40) for biomicroscopy vs. tomography,
      biomicroscopy vs. scanner, and tomography vs. scanner respectively. CONCLUSIONS:
      The central corneal thickenss measurements obtained using Orbscan II tomography
      and the Artemis-2 very high frequency ultrasound scanner can be used
      interchangeably. However, Orbscan II tomography and the Artemis-2 scanner
      measurements cannot be used interchangeably with ultrasound biomicroscopy.

PMID- 24864596
TI  - Protective effects of rosmarinic acid against renal ischaemia/reperfusion injury
      in rats.
AB  - OBJECTIVE: To investigate the potential protective effects of Rosmarinic acid
      (RA) on rats exposed to ischaemia/reperfusion renal injury. METHODS: The
      prospective study was conducted at Abant Izzet Baysal University, Turkey, and
      comprised 21 male Spraque Dawley rats weighing 250-270g each. They were divided
      into three equal groups. Unilaterally nephrectomised rats were subjected to 60
      minutes of left renal ischaemia followed by 60 minutes of reperfusion. Group 1
      had sham-operated animals; group 2 had ischaemia/reperfusion untreated animals;
      and group 3 had ischaemia/reperfusion animals treated with rosmarinic acid. Serum
      creatinine, blood urea nitrogen, tissue malondialdehyde, glutathione peroxidase,
      superoxide dismutase and myeloperoxidase (MPO) activities, and light microscopic
      findings were evaluated. SPSS 17 was used for statistical analysis. RESULTS:
      Treatment of rats with rosmarinic acid produced a reduction in the serum levels
      of creatinine and blood urea nitrogen compared to the other groups. However, no
      statistically significant difference was found. The levels of malondialdehyde and
      myeloperoxidase were decreased in the renal tissue of group 3, while glutathione
      peroxidose and superoxide dismutase levels remained unchanged. The injury score
      decreased in the treatment group rats compared to the untreated group. Rosmarinic
      acid significantly decreased focal glomerular necrosis, dilatation of Bowman's
      capsule, degeneration of tubular epithelium, necrosis in tubular epithelium, and
      tubular dilatation. CONCLUSIONS: Rosmarinic acid prevented ischaemia/reperfusion
      injury in the kidneys by decreasing oxidative stress.

PMID- 24864598
TI  - Pre- and post-operative values of serum CRP in patients undergoing surgery for
      brain tumour.
AB  - OBJECTIVE: To determine the concentration of C-reactive protein in pre- and post
      operative serum samples of brain tumour patients in order to detect the potential
      risks of post-operative infections. METHODS: Serum C-reactive protein was
      measured on pre- and post-operative Day 1, Day 2 and Day 7 in 18 patients who
      underwent surgery for brain tumours. The study was performed at the Neurosurgical
      Ward, Jinnah Postgraduate Medical Centre, Karachi, from May 2007 to April 2008.
      Mean pre-operative patients and control values were compared using Mann-Whitney
      or Wilcoxon tests for comparing between pre- and post-operative values. P-value
      was considered significant at < 0.05. RESULTS: Five (27.7%) of the 18 pre
      operative patients had elevated serum concentrations i.e. > 5.0 mg/L but no
      statistically significant difference was found when compared with healthy
      controls, with mean 4.4 +/- 6.6 and 0.9 +/- 0.7, respectively. Significantly
      raised serum concentrations were observed in all post-operative samples when
      compared with pre-operative samples. Serum CRP concentrations significantly
      increased post-operatively on Day 1, with mean value of 102.9 +/- 82.0 mg/L (p <
      0.0005), and further increased on Day 2 with mean value of 166.9 +/- 128.1 mg/L
      (p < 0.0005), but declined on Day 7, with mean value of 42.7 +/- 63.6 mg/L (p <
      0.005). CONCLUSION: Pre-operative serum C-reactive protein concentrations of 28%
      of the patients were elevated, suggesting an association with brain tumours. Post
      operative serum concentrations were significantly higher than those noted before
      the surgery. Absence of a fall of concentration from peak value on post-operative
      Day 2 or a secondary rise from post-operative Day 7 could be alarming for inter
      current infection.

PMID- 24864599
TI  - Impact of terrorism on health and Hospital Anxiety Depression Scale screening in
      medical students, Karachi, Pakistan.
AB  - OBJECTIVES: To determine the association of terrorism with psychiatric morbidity
      by Hospital Anxiety Depression scale among medical students in Karachi, Pakistan.
      METHODS: The questionnaire based cross-sectional survey was conducted from
      February to March 2011 and comprised students of the Institute of Physical and
      Medical Rehabilitation and the Dow Medical College, Dow University of Health
      Sciences, Karachi. The study tool was a validated Hospital Anxiety Depression
      scale questionnaire. The data was analysed on SPSS 16. Factor analysis was
      performed to check which factors had the most influence. RESULTS: Overall there
      were 1036 respondents. The impact of terrorism on physical, social and mental
      health was 40 (3.9%), 178 (17.2%) and 818 (79%) respectively. There was an
      association of terrorism in 980 (84.6%) respondents with psychiatric morbidity.
      CONCLUSION: There was an association of terrorism with psychiatric morbidity in
      majority of respondents. The significant risk factors were age, gender, physical,
      mental and social health and the desire to live in Pakistan.

PMID- 24864600
TI  - Frequency, clinical presentation and microbiological spectrum of candidemiain a
      tertiary care center in Karachi, Pakistan.
AB  - OBJECTIVE: To document the frequency, clinical presentation, outcome and spectrum
      of species in Candida blood stream infection. METHODS: A prospective, descriptive
      cohort study was conducted from June 1st till November 30th 2012 at the Sindh
      Institute of Urology and Transplantation in Karachi, Pakistan. All patients > or
      = 15 years of age from nephrology, urology, gastroenterology, oncology or
      intensive care units with candidemia were included. RESULTS: Of 2457 positive
      blood cultures, 145 (6%) were positive for Candida species in 121 patients.
      Seventy seven patients were included for further analysis as clinical data was
      available for these. The majority of patients had renal failure (89.6%) and 44%
      had femoral line. Non- albicans species were isolated in 70 (90.9%) patients;
      Candida parapsilosis in 28 (36.4%), C. lusitaniae in 23 (29.9%), C. tropicalis in
      16 (20.8%), C. glabrata in 3 (3.9%) with only 7 (9.1%) with C. albicans.
      Mortality was 23.4% (18 patients). CONCLUSION: Frequency of candidemia and
      species distribution with predominantly non-albicans candida in our study is
      similar to that reported from other developing countries. Mortality is high. The
      majority of our patients had line related candidemia. Therefore prevention of
      line infection must be our top priority.

PMID- 24864601
TI  - Cystatin C levels in healthy kidney donors and its correlation with GFR by
      creatinine clearance.
AB  - OBJECTIVE: To determine Serum Cystatin C (S.CysC) levels in healthy potential
      kidney donors and its correlation with Serum Creatinine (S.Cr), Glomerular
      filtration rate (GFR) by 24 hour urinary Creatinine clearance (CCL) and GFR by
      formulae of Cockcroft Gault (CCG) and Modification of diet in Renal Disease
      (MDRD). METHODS: A Cross sectional study was conducted at Sindh Institute of
      Urology and Transplantation (SIUT), Karachi, between June and December 2012. One
      hundred and three potential healthy kidney donors were enrolled in the study to
      measure their S.CysC and correlate it with S.Cr, CCL and GFR by CCG and MDRD.
      Statistical analysis was done by SPSS 17. RESULTS: The mean age of the healthy
      kidney donors was 32.19 + 8.27 years with a M:F ratio of 1.86:1. The mean Serum
      Creatinine (S.Cr) was 0.86 + 0.18 mg/dl and mean S.CysC was 0.88 + 0.12 mg/dl.
      S.CysC showed significant correlation with S.Cr (r = 0.78, p < 0.001), CCL (r =
      0.67, p < 0.001), GFR CCG (r = 0.54, p < 0.001) and GFR MDRD (r = 0.67, p <
      0.001). Correlation of S.CysC was better than S.Cr for CCL, S.Cr (0.60) vs S.CysC
      (0.67) and GFR CCG, S.Cr (0.41) vs S.CysC (0.54). Correlation was comparable for
      MDRD, S.Cr (0.67) vs S.Cys (0.67). CONCLUSION: S.CysC is better marker of kidney
      function in potential healthy kidney donors. It is a reliable, convenient and
      economical marker that can be used especially in routine clinical practice.

PMID- 24864602
TI  - Smoking among high school students of an area with medium socioeconomic status.
AB  - OBJECTIVE: To observe the smoking patterns among high school students in Sarakhs
      County, Iran. METHODS: This is a cross sectional school based survey. The study
      population was 943 high school students grade 9-12, from Sarakhs County in study
      year 2010-2011. Study tool was a self-administrated questionnaire. RESULTS: From
      943 participating students, 181(19.2%) had history of smoking. The mean age of
      smokers was 16.59 +/- 1.1, and the mean age of initiating smoking was 14.35 +/-
      2.1 years. Of the smokers, 121 (66.9%) were male and 124 (68.7%) students were
      aware of smoking hazards. Public broadcasting, family, and newspapers were the
      most common sources of students' knowledge about smoking. Recreation and
      entertainment, peer group impact, and curiosity were the most frequent
      predisposing factors for smoking from students' perspectives. The relationship
      between smoking and school type, field of study, school failing, and having a
      smoker father, brother or friend was significant (p < 0.001). The concomitant use
      of illegal drugs was more common between smoker students; marijuana 4.9, alcohol
      1.2, Psychoactive Pills 2.5 and Betel Nut (Nas) 3.4 times were more common.
      CONCLUSION: This study showed that smoking prevalence among high school students
      of an area with average socioeconomic status (Sarakhs County) is similar to that
      reported by most of the other Iranian studies, and compared to a few studies it
      was even lower. Our results are supportive for the programmes that aim to change
      high risk behaviours simultaneously.

PMID- 24864603
TI  - Age related clinical manifestation of acute bacterial meningitis in children
      presenting to emergency department of a tertiary care hospital.
AB  - OBJECTIVE: To determine the signs and symptoms of acute bacterial meningitis
      (ABM) in different age grops of a paediatric population. METHODS: The
      retrospective study comprised patients who had been admitted through the
      Emergency Department of Aga Khan University Hospital, Karachi with the relevant
      diagnosis from September 2009 to September 2011. Case record forms were used to
      collect data from patient files. Data was collected using variables such as age,
      gender, presenting complaints, clinical signs and symptoms, computed tomography
      scan findings and final outcome of patients. There was a minimal risk of breach
      in patient confidentiality. SPSS 19 was used for data analysis. RESULTS: A total
      of 192 patietns were enrolled. The presenting complaint in 165 (86%) patients was
      fever; vomiting in 93 (48.43%); and 49 (52.68%) of them were more than 5 years
      old. Irritability was present in 54 (28.12%) children, of whom 27 (50%) were less
      than one year. Fits were present in 47 (24.47%) cases out of which 21 (44.68%)
      were less than one year. Neck stiffness and signs of meningeal irritation,
      Kerning's sign and Brudzincski's sign, were present in 53 (27.60%) patients; 26
      (13.54%); and 18 (9.3%) respectively. These signs were more common in children
      over 5 years of age, reflected by 29 (54.7%), 16 (61.5%) and 11 (61.11%) patients
      respectively. On presentation, headache was found in 77 (40.10%) children among
      whom 56 (72.72%) were over 5 years. Besides, 151 (78.6%) patients required
      admission to the ward, while 40 (20.8%) were admitted in High Dependancy
      Unit/critical care units Adverse outcome was observed in 6 (3.12%) patients.
      CONCLUSION: Younger children with acute bacterial meningitis presented with non
      specific signs and symptoms. Headache and signs of meningeal irritation were
      common findings in children over 5 years.

PMID- 24864604
TI  - The relationship of mast cells and angiogenesis with prognosis in renal cell
      carcinoma.
AB  - OBJECTIVE: To evaluate the effects of mast cell count and angiogenesis on the
      prognosis of renal cell carcinoma. METHODS: The retrospective study was conducted
      at the Harran University, Sanliurfa, Turkey, and included 64 cases with diagnosis
      of renal cell carcinoma between 2002 and 2012. Immunohistochemical analysis was
      performed on paraffin sections using the standard streptavidin-biotin
      immunoperoxidase method. CD31 antibodies were used to identify microvessels in
      tumoural tissues. The microvessel density was calculated using a serological
      method. The mean vascular density was equivalent to the vascular surface area (in
      mm2) per unit tissue volume (in mm3) (MVD = mm3). Mast cells tryptase antibody
      was used to evaluate the mast cell count in tumoural and non-tumoural tissues.
      The relationship between mast cell count and microvessel density was evaluated
      and compared with stage, grade, tumour diameter, and age. RESULTS: The mast cell
      count in the tumoral tissue of renal cell carcinoma was significantly higher
      compared with non-neoplastic renal tissue (p < 0.001). A significant relationship
      was found between the mast cell count in tumoral tissue and stage, grade, and
      tumour diameter (p < 0.001). However, no relation was found with age (p > 0.05).
      The intratumoural mast cell count in clear cell renal carcinoma was significantly
      higher compared with non-clear variety (p = 0.001). No significant relationship
      was found between microvessel density, age, stage, diameter, or grade of the
      tumour and tumoral mast cell count (p > 0.05). CONCLUSION: No significant
      association was found between the number of mast cells in tumoral tissue and
      microvessel density. Further studies are needed to demonstrate the effect of mast
      cells on angiogenesis in renal cell carcinoma.

PMID- 24864605
TI  - Clinical types of tinea capitis and species identification in children: an
      experience from tertiary care centres of Karachi, Pakistan.
AB  - OBJECTIVE: To study the clinical types of Tinea Capitis and identify species in
      children reporting to two tertiary care centres of Karachi, Pakistan. METHODS:
      The descriptive, cross-sectional study was conducted at the Dermatology
      Outpatients' Department, PNS Shifa Hospital and the Institute of Skin Diseases,
      Karachi, from January 1, 2008 to December 31, 2009. It comprised 202 children
      with clinical diagnosis of tinea capitis, confirmed by skin scrapings, showing
      fungal hyphae and spores in 10% potassium hydroxide on direct microscopy. Wood's
      lamp examination was carried out and the scrapings were cultured on Sabouraud's
      agar. A detailed dermatological examination was performed for evidence of fungal
      infection elsewhere in the body. SPSS 19 was used for data analysis. RESULTS:
      Male-to-female ratio was 1.1:1 and age ranged from 1 to 14 years.The commonest
      clinical type gray patch was observed in 71 (35.1%) of the patients, black dot in
      63 (31.2%), kerion in 50 (24.8%), favus in 10 (5.0%), diffuse pustular in 6
      (3.0%), and diffuse scale in 2 (1.0%) patients. The most frequent species grown
      on culture was Trichophyton (T). Soudanense, followed by T. Tonsurans, T.
      Schoenleinii, and T. Mentagrophytes respectively. CONCLUSION: Most of the
      patients of Tinea capitis presented with gray patch and black dot variety. The
      most common species identified by culture was Trichophyton Soudanense. Disease
      was equal in both gender and predominantly affected the population belonging to
      low and middle socioeconomic class.

PMID- 24864606
TI  - Results of level-II oncoplasty in breast cancer patients: an early experience
      from a tertiary care hospital in Pakistan.
AB  - OBJECTIVE: To assess the oncologic and cosmetic outcomes for breast cancer
      patients who underwent breast conservation therapy using Level II oncoplasty
      techniques. METHODS: The prospective, non-randomised and descriptive study was
      conducted at the Department of Surgery, Unit IV of Civil Hospital, Karachi, from
      December 2009 to November 2011 in which 21 consecutive women with breast
      carcinoma who underwent wide local excision with remodeling mammoplasty were
      enrolled. All patients were reviewed by the surgeon and medical oncologist every
      3 months for the first year. A grading system of 5-1 (excellent to poor) was
      employed and those with 3 or more were considered to have acceptable results.
      RESULTS: The mean patient age was 45.38 +/- 10.09 years (range: 26-70); 11
      (52.3%) were premenopausal and 10 (47.7%) were postmenopausal; and 5 (27.8%) had
      family history of breast cancer. The mean size of the tumour determined by
      histology was 59.9 +/- 3.18 mm (range: 25-150). Eight (30%) patients received
      preoperative chemotherapy to downsize the tumour. Three (14.2%) patients received
      preoperative radiotherapy. Mean operative time was 1.59 +/- 0.52 hours (range: 1
      2.5 hours). Mean volume of breast tissue excised from the breast containing the
      tumour was 545.27 +/- 412.06 cm3 (range: 43.70-1456). Assessment of excision
      margins showed no tumour at the margins of 19 (90.4%) patients. Two (9.5%)
      patients had close but negative margins. The mean hospital stay was 7.10 +/- 3.30
      days (range: 4-15). There were early complications in 4 (19%) patients. One
      (4.76%) patient had late complications. Two (9.5%) patients developed tumour
      recurrence; both had an ipsilateral tumour recurrence. None of the patients
      developed metastases and one died of cardiac problem. Twenty (95.2%) patients had
      an acceptable post-surgical cosmetic result. CONCLUSION: Level II oncoplasty was
      a safe option in breast conservation allowing large-sized and difficult-location
      tumour excision with good cosmetic outcome in the study group. There is a need to
      increase the awareness and acceptance of this new technique not only amongst
      patients but also doctors.

PMID- 24864607
TI  - Nutrient intake and growth indices for children at kindergartens in Shiraz, Iran.
AB  - OBJECTIVE: To evaluate energy and nutrient intake and determine growth indices
      for pre-school children in Iran. METHODS: The study was conducted from June to
      September 2010 and included 150 children aged between 3 and 5 years who attended
      kindergartens in Shiraz, Iran. Following a measurement of the participants'
      height and weight, three 24-hour dietary recalls were completed based on
      interviews with their parents. The data was entered into various computer
      softwares. The prevalence of underweight, stunting, wasting, at-risk-of
      overweight and overweight children was then calculated, and energy and nutrient
      intake was compared with the recommended values. RESULTS: The mean intake of
      energy, calcium and iron for the children were less than the recommended values.
      In contrast, the mean intakes of carbohydrate, protein, zinc and vitamin C were
      higher than the recommendations. Fat intake, however, was within the Acceptable
      Macronutrient Distribution Range. In addition, the rates of prevalence of the
      underweight, stunting, wasting, and overweight or at-risk-of-overweight were
      found to be 27 (18.6%), 37 (25.5%), 18 (12.4%) and 34 (23.4%), respectively.
      Finally, underweight children had lower intake of energy, carbohydrate, protein,
      fat, iron and zinc, while overweight or at-risk-of-overweight ones had higher
      intake of protein, calcium and zinc. CONCLUSION: There is a need for children in
      kindergartens of Shiraz to improve their mean intake of energy, calcium and iron.
      Moreover, about one-fourth of the children were stunted and about the same
      proportion were either overweight or at the risk of being so.

PMID- 24864608
TI  - Frequency and clinicopathological correlations of histopathological variants of
      idiopathic focal segmental glomerulosclerosis in nephrotic adolescents.
AB  - OBJECTIVE: To determine the frequency and clinicopathological correlations of
      focal segmental glomerulosclerosis variants in adolescents with idiopathic
      nephrotic syndrome. METHODS: All consecutive adolescents (12 to 18 years) who
      presented with idiopathic nephrotic syndrome in the period, January 2009 to
      December 2012, and in whom the histological diagnosis of focal segmental
      glomerulosclerosis was made on renal biopsies, were included in this prospective
      study. Their clinical, laboratory and histopathological features at the time of
      presentation or biopsy were noted from the case files and the biopsy reports.
      RESULTS: Among 50 adolescents, 34 (68%) were males and 16 (32%) females.The mean
      age was 15.14 +/- 2.3 years. The mean duration of disease was 6.3 +/- 11.2
      months.The mean serum creatinine was 0.96 +/- 0.82 mg/dl. The mean 24-hour
      urinary protein excretion was 3.8 +/- 0.68 grams. Biopsy indications were steroid
      resistant nephritic syndrome in 15 (30%), steroid-dependant nephritic syndrome in
      19 (38%) and adolescent nephritic syndrome in 16 (32%) cases. Among the focal
      segmental glomerulosclerosis variants, 40 (80%) were "not otherwise specified",
      followed by the collapsing variant, which accounted for 8 (16%) cases. The tip
      and cellular variants, both were found in one (2%) case each. Among the
      histological features, global glomerulosclerosis was found in 23 (46%) cases, and
      segmental scarring/collapse in all (100%). A variable degree of tubular atrophy
      and interstitial fibrosis was noted in 44 (88%) cases. CONCLUSION: The results
      from this study indicate that the pattern of focal segmental glomerulosclerosis
      variants differs markedly in adolescents compared with younger children.

PMID- 24864609
TI  - From the year 2050; a glimpse of medical education in the future.
AB  - This article is supposedly sent from the future; the year 2050.The author
      describes the evolution of medical education in 21st century and focuses on the
      challenges ahead of today. The long years of laborious medical education and
      complex irrelevant curriculum would instigate a loud debate to amend the current
      educational system. Gradually, the health system would plateau, as rapid turn out
      of voluminous new information would not be efficiently channelized to actual
      patient care. Patient dissatisfaction would increase and the clinician-researcher
      model of physician would be dubious. Consequently, substantial revisions would be
      inevitable. By year 2050, the author hypothesizes that the system of continuing
      medical education would be replaced by continuing professional development. The
      number of years to be a full certified specialist would be significantly
      shortened and clinicians would be trained to work in a highly specialized
      multidisciplinary framework. After a common core medical curriculum, health care
      professionals would adapt different tracks to be physicians, allied health
      workers and medical scientists. Programme designs would allow early hands on
      experience in a patient-specialist programme. The main outcomes of patient
      management would not be limited to diagnosis or treatment of ailment, and would
      fundamentally incorporate quality of life issues. An early commitment to medical
      specialty would enable clinicians to focus on their specialized domains, master
      their skills at the best learning age and retain their energies for tomorrow.

PMID- 24864610
TI  - Stillbirth--a neglected priority: understanding its social meaning in Pakistan.
AB  - Despite being ranked 3rd among the countries having highest burden of
      stillbirths, it remains a neglected priority in Pakistan. We review the evidence
      regarding social and biomedical understanding of stillbirths by both communities
      and healthcare providers. The terminology used to define stillbirth worldwide
      remains inconsistent. Not only do the health professionals mis-classify and under
      report stillbirths, but also the parents and families are unclear about the
      difference between miscarriage, stillbirth and early neonatal deaths. Stillbirths
      occur more in poor families and are not recognised by tradition and religion as a
      loss comparable to a newborn who was born alive. There is need to understand
      perspective of communities and healthcare providers to identify prevention and
      management strategies along with providing support for coping with the
      implications of stillbirths. Future government policies on stillbirths must be
      informed by the influence of culture on the attitudes, beliefs and practices of
      the communities and the healthcare providers.

PMID- 24864611
TI  - Detection of eating disorders in 16-20 year old female students--perspective from
      Islamabad, Pakistan.
AB  - There are no studies on eating disorders in Pakistani adolescent girls. This
      study was conducted to determine the opinions, and behaviours pertaining to
      dieting and body size among 16 to 20 year old female school and college students
      in Islamabad, Pakistan. This was done through a five-item questionnaire to
      determine the SCOFF score. The SCOFF acronym has been derived from 'S' from the
      word "sick" in question number 1.'C' from the word "control" in question number
      2. The 'O' comes from the word 'one' in the original question number 3; this
      original question number 3 of the SCOFF asks about having lost more than 'one'
      stone weight in the past three months. This question was rephrased to read as
      whether more than 15 pounds or 6 kilogrammes have been lost. The two 'F's come
      from questions number 4 and 5 denoting words "fat" and "food", respectively. A
      total of 1,134 female students participated in the study and 736 (64.9%)
      respondents scored two or higher on the SCOFF scale; 461 (66.5%) out of 693 were
      aged 16 to 18, while 275 (62.4%) out of 441 were aged 19 to 20. Results indicated
      a need for developing clinical practice guidelines for general practitioners and
      paediatricians to proactively identify and treat potential eating disorders in
      young Pakistani women.

PMID- 24864612
TI  - Reproductive and gynaecological issues in Saudi women with end stage renal
      disease.
AB  - Women with End Stage Renal Disease (ESRD) have hormonal imbalance leading to
      gynaecological and reproductive disturbances. The objective of this study was to
      see the reproductive and gynaecological problems associated with ESRD. Forty
      Saudi Arabian women with a diagnosis of ESRD for a period of 60 months were
      interviewed at the dialysis unit of King Fahd University Hospital, Al Khobar.The
      average age was 51.5 +/- 17.1 years with a range of 19-90 years. Eighteen (45%)
      were premenopausal with a mean age of 36.5 +/- 11.1 years. Diabetes mellitus and
      Hypertension was the cause of ESRD in 29 (72.5%). Out of 18 menstruating women
      11(61.1%) had irregular periods. Only 2 had children after ESRD was diagnosed.
      Thirty-three (82.5%) women did not have their regular mammograms and 25 (73.5%)
      had no pap smears. Our study shows that majority of women with ESRD have
      gynaecological and reproductive issues which are being neglected.

PMID- 24864613
TI  - Congenital chloride losing diarrhoea.

PMID- 24864614
TI  - Non-Hodgkin's thyroid lymphoma associated with Hashimoto's thyroiditis.
AB  - We report two cases of thyroid lymphoma. First was of a 54-year-old lady who
      presented with a 10 year history of goiter. Examination revealed an enlarged
      thyroid gland extending sub-sternally, with no palpable lymph nodes. She had been
      on thyroxine for 4 months, due to a high TSH with positive antibodies. Fine
      needle aspiration cytology of thyroid showed Hashimoto thyroiditis (HT). A total
      thyroidectomy was done because of pressure symptoms. Histopathology revealed HT
      in right lobe and Diffuse Large B-cell Non-Hodgkin's lymphoma (DLBCL) in left
      lobe. Second case was of a 30 year-old man who presented with dyspnoea secondary
      to rapidly enlarging thyroid. On examination, thyroid was diffusely enlarged
      together with palpable lymph nodes. His TSH was elevated & Anti-TPO antibodies
      were positive suggesting an autoimmune etiology. Ultrasound showed, an ill
      defined heterogeneous mass in the left lobe of thyroid gland with multiple
      enlarged lymph nodes. Ultrasound guided thyroid core biopsy revealed DLBCL.

PMID- 24864615
TI  - Aggressive angiomyxoma: swirled configuration on ultrasound and MR imaging.
AB  - Aggressive angiomyxoma is a rare, myofibroblastic tumour, of pelvi-perineum of
      young women. It is a slow growing, low grade neoplasm with a high risk of
      recurrence following initial resection. Aggressive angiomyxoma is often
      clinically misdiagnosed because of its variable presentation as a soft tissue
      mass of the vulva, perianal region, buttock or pelvis. It displays translevator
      extension with growth around the perineal structures. Fewer than 150 cases have
      been reported in the literature since 1983. Imaging is important to determine the
      extent of the lesion. We present layered configuration of the mass on ultrasound
      and Magnetic Resonance Imaging in a 40 years old woman with a left pelvi-
      perineal mass since 5 years. Histapathology after excision gave a diagnosis of
      Aggressive Angiomyxoma.

PMID- 24864616
TI  - Does pernio cause nail dystrophy?
AB  - Pernio is an abnormal inflammatory response to moisture and cold. It is
      characterized with inflammatory, erythema or violet, painful or itchy cutaneous
      lesions affecting distal extremities, particularly the fingers and toes. It is
      more common in women. A literature search showed no reports of nail deformities
      due to pernio. Here, we present a pernio case who developed nail deformities
      after extended exposure to cold, if combined with other facilitating factors.

PMID- 24864617
TI  - Craniofacial fibrous dysplasia--a Morbid presentation.
AB  - Fibrous dysplasia is grouped under fibro-osseous lesions with developmental
      anomaly of bone forming mesenchyme that manifests as a defect in osteoblastic
      differentiation and maturation. This paper describes a case of 28 yrs old female
      who presented with swelling on right side of face, nostril and intraoral swelling
      on right half of hard palate since 1-year. The diagnosis was based on clinico
      radiological and histopathological investigations. The appropriate management of
      patient included surgical modality along with placement of obturator to fill the
      defect. Follow up was done and till date there is no recurrence.

PMID- 24864618
TI  - Management of intramuscular venous malformations of the masseter muscle.
AB  - Less than 1% of vasoformative tumours throughout the body occur in skeletal
      muscle and 15% of them arise in head and neck musculature. The masseter muscle is
      the most frequent site and accounts for approximately 5% of all intramuscular
      vascular malformations in the head and neck region. Masseteric venous
      malformations have a typical clinical presentation and imaging characteristics
      that should allow clinicians to distinguish them from other abnormalities
      presenting in this area. We present seven cases of these unusual intramasseteric
      venous malformations and the diagnosis and management of these lesions is
      discussed. The diagnosis was made on clinical grounds and was confirmed on MRI.
      All underwent surgical excision through a facelift approach and were successfully
      removed from within the substance of the masseter muscle with preservation of the
      facial nerve. Venous malformations within the masseter are rare but are easy to
      diagnose and can be reliably surgically excised without complications.

PMID- 24864619
TI  - Insulin and glucagon-like peptide receptor agonist (GLP 1 RA) combinations.
AB  - This review analyses a recent advance in diabetes pharmacotherapeutics: the
      combination of insulin and glucagon-like peptide 1 receptor agonists (GLP 1 RA).
      It describes the rationale for such a combination, and discusses the impact of
      such therapy on glycaemic control. The paper also assesses other benefits of the
      combination, and provides a practical framework for pragmatic, rational use of
      this treatment.

PMID- 24864620
TI  - Asymptomatic atrial fibrillation and stroke risk.

PMID- 24864621
TI  - Blood products used in exchange transfusion should also be screened for opioids.

PMID- 24864622
TI  - Effects of papaya leaves on thrombocyte counts in dengue--a case report.
AB  - Dengue fever is on the rise in developing nations like India, Pakistan, Sri Lanka
      and Bangladesh. There is no antiviral chemotherapy or vaccine for dengue virus
      and management of the disease is done on supportive measures. The decline in the
      thrombocyte count leads to dengue haemorrhagic fever accounting for complications
      and mortality. Oral administration of Carica papaya leaves extract is said to
      have a positive impact on thrombocyte count. A 23-year-old man was administered a
      calculated dose for five days. Blood samples were tested for complete blood count
      before and after the administration of the juice. Thrombocyte count had increased
      from 28000/micro liter to 138000/micro liter at the end of five days. We present
      our experience here.

PMID- 24864623
TI  - Studying freaks?: Medical students and the community.

PMID- 24864624
TI  - Pakistan can progress with sensible family planning.

PMID- 24864625
TI  - Cerebral venous sinus thrombosis presentation in emergency department in Van,
      Turkey.
AB  - OBJECTIVE: To exmaine the distribution of age, gender, time between onset and
      presentation, clinical findings, predisposing factors, platelet distribution
      width, mean platelet volume values and neuroimaging findings, together with the
      treatment regime and the outcome for patients of cerebral venous sinus
      thrombosis. METHODS: The retrospective, descriptive cross-sectional study was
      conducted at Yuzuncu Yil University, Medical Faculty Hospital in Van, Turkey,
      comprising 51 cases diagnosed with cerebral venous sinus thrombosis between
      January 2008 and September 2011. The diagnosis was based on the results of
      clinical evaluation, cranial magnetic resonance imaging and venography. SPSS 16
      was used for statistical analysis. RESULTS: Overall, 43 (84.3%) of the cases were
      female, and 8 (15.7%) were male.The average age was 32 +/- 11.13 years The most
      frequent symptom was headache in 41 (80.4%) cases. The postpartum period was one
      of the most observed predisposing factors in 17 (33.3%) patients. The magnetic
      resonance imaging was normal in 35 (68.6%) cases, but in all of the cases,
      magnetic resonance venography was abnormal. Topographically, the most frequent
      involvement was transverse sinus in 40 (78.4%) cases. Besides, 50 (98%) patients
      were discharged following full recovery or mild sequela and only 1 (2%) case had
      severe sequela. CONCLUSION: Patients presenting with headache should be examined
      carefully in the emergency department. Early diagnosis and treatment with
      clinical and neuroimaging techniques for such patients is recommended.

PMID- 24864626
TI  - Blunt thoracic trauma--an analysis of 264 patients in Rawalpindi, Pakistan.
AB  - OBJECTIVE: To analyse the outcome in terms of morbidity and mortality in blunt
      thoracic trauma patients in tertiary care hospitals, Rawalpindi. METHODS: The
      prospective study was conducted from March 2008 to February 2012 in surgical
      wards of public and private sector hospitals in Rawalpindi. A total of 221
      patients were included from the Combined Military Hospital during 2008-10, and 43
      patients from the Heart's International during 2011-12. The patients reported to
      emergency department within 48 hours of trauma. All patients were subjected to
      detailed history and respiratory system examination to ascertain fracture of
      ribs, flail segment and haemopneumothorax. The diagnosis of chest wall injuries,
      parenchymal pulmonary injuries and pleural involvement were made on the basis of
      chest radiographs and computed tomography scan of the chest. The lung contusion
      was assessed by the number of lobes involved. SPSS 19 was used for statistical
      analysis. RESULTS: Of the 264 patients in the study, 211 (80%) were males and 54
      (20%) females. The overall mean age was 44.8 +/- 17.1 years. Over all morbidity
      was 222 (84.2%); morbidity (minor) was 128 (48.5%), and morbidity (major) was 94
      (35.7%). Mortality was 26 (9.8%) and 16 (6%) cases had normal outcome.
      CONCLUSION: Early identification and aggressive management of blunt thoracic
      trauma is essential to reducing significant rates of morbidity and mortality.

PMID- 24864627
TI  - Association between oxidative stress index and serum lipid levels in healthy
      young adults.
AB  - OBJECTIVES: To investigate the relationship between lipid levels and oxidative
      stress index in healthy young adults. METHODS: The study was camed out at the
      Department of Emergency Service, Faculty of Medicine, Cumhuriyet University,
      Sivas, Turkey, between January 2011 and July 2012. A total of 100 healthy adult
      volunteers were enrolled in the study. Venous blood samples (10 ml) were
      collected from all individuals, and serum lipid parameters, total antioxidant
      capacity and total oxidative levels were studied. SPSS 15 was used for
      statistical analysis. RESULTS: Overall, there were 84 (84%) males and 16 (16%)
      females. The mean age fo the male population was 30 +/- 3 years, while that of
      the females was 31 +/- 3 years. Overall age ranged from 25 to 35 years. A
      statistically significant correlation was found between the oxidative stress
      index and serum cholesterol (p < 0.001; r = 0.596), triglyceride (p < 0.001; r =
      0.476) and low-density lipoprotein levels (p < 0.001; r = 0.318). However, no
      significant correlation was found between oxidative stress index and serum high
      density lipoprotein levels (p = 0.564; r = 0.058). CONCLUSION: The results showed
      that even at an early age, there is a direct linear correlation between oxidative
      stress and serum lipid levels.

PMID- 24864628
TI  - Characterisation of up-regulated immunoglobulins in patients with chronic
      rhinosinusitis.
AB  - OBJECTIVE: To evaluate the role of immunoglobulins in patients of chronic
      rhinosinusitis. METHODS: Patients were recruited from the Ear, Nose, Throat, Head
      And Neck Surgery section of Mazandaran University of Medical Sciences, Sari,
      Iran, from December 2011 to August 2012. Immunoglobulin G, IgG1, IgG2, IgG3, IgG4
      were evaluated. Salivary IgA was assessed by direct immunoenzymatic
      determination. The quantifications of serum IgG, IgG1, IgG2, IgG3, IgG4 and
      salivary IgA was performed through nephelometric procedure. Serum IgE was
      measured by enzyme-linked immunoabsorbent assay. SPSS 15 was used for statistical
      analysis. RESULTS: Of the 50 patients, 22 (44%) were males and 28 (56%) were
      females. The overall age ranged from 1 to 67 years with a mean of 28.06 +/-
      15.49. There was significant changes in levels of IgG, IgG1, salivary IgA and IgE
      (p = 0.001). Significant difference was noted for IgG2 (p = 0.03) and in IgG4 (p
      = 0.01). There was no significant alteration in IgG3 level (p = 0.3). CONCLUSION:
      There was high prevalence of humoral immune alterations both in local and
      systemic response to chronic inflammation in the patients, which suggests that
      assessment of immunoglobulin before clinical evaluation and management could be
      important.

PMID- 24864629
TI  - Malignant mediastinal mass in children: a single institutional experience from a
      developing country.
AB  - OBJECTIVE: To determine the clinical spectrum and management outcomes of
      paediatric patients with modiastinal mass in a Karachi hospital. METHODS: Medical
      records of all cases of mediastinal masses in children diagnosed and treated
      between January 2005 and December 2011 were retrospectively reviewed to evaluate
      the mode of presentation, histopathological diagnosis, radiologic findings and
      management outcomes at Aga Khan University Hospital, Karachi, Pakistan. SPSS 19
      was used for data analysis. RESULTS: A total of 37 patients of mediastinal masses
      were identified, and malignancy was found in 32 (86%) cases. The median age at
      diagnosis was 9 years (interquartile range: 4.7 years). Lymphoma 23 (72%) and
      leukaemia 8 (25%) were the most common causes of mediastinal mass. Nonspecific
      symptoms such as fever 26 (81%), cough 15 (47%) and dyspnoea 12 (37%) constituted
      the most commonly presenting complaints. Overall, 22 (68.7%) patients underwent
      surgical procedures (complete/partial resection of mass); local lymph node biopsy
      was performed in 5 (15.6%) cases; and computed tomography or ultrasound-guided
      biopsy was done in 2 (5.4%) patients. Besides, 27 (84.4%) patients were admitted
      to paediatric intensive care unit for supportive care, and assisted ventilation
      was required in 20 (62.5%) patients. The mean length of hospital stay was 9.3 +/-
      6 days. None of the patients died due to complications related to mediastinal
      mass or diagnostic procedure. CONCLUSIONS: Although mortality rate has reduced
      significantly with refinements in the management protocols, but a high index of
      suspicion and comprehensive multidisciplinary approach is crucial to improve the
      morbidity and mortality.

PMID- 24864630
TI  - Evaluation of residents' thoughts about giving the news of death.
AB  - OBJECTIVE: To assess behaviours and attitudes of residents toward giving news of
      death in emergency department and other departments. METHODS: The study was
      conducted between 1st and 7th December, 2012, in an urban hospital in Ankara,
      Turkey. It used a questionnarie that was filled by 100 residents from different
      disciplines of medicine. Categorical variables were analysed with Chi-square and
      Fisher's exact tests and continuous variables were analysed with Mann Whitney
      test. The level of statistical significance was set at 0.05. RESULTS: The most
      difficult cases to notify were those of unexpected and sudden deaths (n = 51;
      51%) followed by deaths of children (n = 36; 36%). While 60% (n = 60) of the
      study group reported a need for training in this area, but there was no
      association between having difficulty in notifying a death and expressing the
      need for training (p = 0.187). Residents who had difficulty in notifying death
      informed the patient's close ones more often during resuscitation (p = 0.049) and
      requested for security staff more often during the final briefing compared with
      the group that did not express having difficulty (p < 0.001). CONCLUSION:
      Notifying death is still a challenging issue in medicine. Instead of educational
      efforts, security measures may be more beneficial and comforting for residents
      who have difficulty in conveying the news.

PMID- 24864631
TI  - Comparison of CAD risk factors in abdominal obesity versus general obesity with
      normal WC in adult males.
AB  - OBJECTIVE: To compare the presence of coronary artery disease risk factors in
      patients with abdominal obesity versus generalised obesity and to determine the
      probability of developing the disease in both groups. METHODS: The cross
      sectional study was carried out at the Department of Medicine, Combined Military
      Hospital, Okara, from January 2012 to April 2013. Using consecutive sampling, 785
      outdoor healthy adult males were enrolled. Body mass index > 25kg/m2 and waist
      circumference > 90cm defined obesity and abdominal obesity respectively. Blood
      pressure > 140/90mmHg defined Hypertension. All the subjects underwent BSF,
      electrocardiogram, Lipid profile, personality and physical activity assessment.
      Risk estimation was done using Eric Brittain scoring system. Data was analysed
      using SPSS 16. RESULTS: In patients with abdominal obesity, 583 (99.2%)
      individuals had at least 1 risk factor for coronary artery disease, while in
      those with generalised obesity this prevalence was 96.5% (n = 191). In patients
      with abdominal obesity, 52.9% had more than 4% risk of developing the disease in
      the next 6 years compared to 36.9% individuals with generalised obesity.
      CONCLUSION: Both increasing body mass index and waist circumference are
      associated with increased risk of developing coronary artery disease, with
      significantly higher risk prevalence in the latter group. Moreover, those with
      abdominal obesity had a higher risk of developing CAD in next 6 years as compared
      to those with generalised obesity. Thus waist circumference offers additional
      prognostic information beyond body mass index.

PMID- 24864633
TI  - The evidence of mother to child transmission of hepatitis B virus infection in
      Pakistan and the need for hepatitis B immunization policy change.
AB  - OBJECTIVE: To establish the hepatitis B surface antigen and hepatitis B 'e'
      antigen seroprevalence of mothers and their children aged 6-36 months and to
      assess the risk of hepatitis B transmission occurring in infants born to
      hepatitis B surface antigen positive mothers in Pakistan. METHODS: Mothers and
      their children were selected from eight districts of three provinces that have
      been identified as high hepatitis B prevalence areas between May 2010 to February
      2011. Ages of the children and their vaccination status were obtained from the
      lady health workers' registers and also verified from the mothers. Five ml of
      blood was drawn from all the children and their mothers for testing. All sera
      were tested for anti-hepatitis B. Those found negative were run for HBsAg the
      sueface antigen and those positive for it were further run for hepatitis B 'e'
      antigen All tests were run on Abbott machine using chemiluminesence method. EPI
      info 12 was used for statistical purposes. RESULTS: A total of 1561 mothers and
      their 1612 children were tested. Among the mothers, 590 (37.8%) were hepatitis B
      antibody positive. Remaining 971 (62.2%) samples were tested for surface antigen
      and 123 (12.7%) were found positive of which 27 (22%) showed HBeAg positivity.
      Out of 1612 children tested, 975 (60.5%) were positive. Remaining 637 (39.5%)
      were tested for surface antigen and 49 (8%) were found positive of which 24 (49%)
      were HBeAg positive with a perinatal hepatitis B virus transmission rate of 5.4%
      by 12 months of age. Of the 123 surface antigen positive mothers, 18 (14.6%) had
      children who were also positive, while of the 1489 children born to the 1438
      surface antigen negative mothers, 31 (2.1%) were positive. Children born to
      surface antigen positive mothers had eight times higher risk of getting hepatitis
      B virus infection and the risk rose to 17 times if the mother was also HBeAg
      positive. Hepatitis B vaccination record showed that 1229 (76.25%) children were
      vaccinated at six weeks with pentavalent vaccine, but despite vaccination 33
      (2.6%) became surface antigen positive. No vaccination was received by 320
      (19.9%) children and out of these 16 (5%) became surface antigen positive.
      Moreover, the vaccinated and unvaccinated children born to surface antigen
      positive mothers were nine and 11 times respectively more likely to be exposed to
      the risk of hepatitis B virus transmission relative to vaccinated children born
      to surface antigen negative mothers. CONCLUSIONS: Hepatitis B vaccination given
      at 6, 10 and 14 weeks of birth is not sufficiently protective, indicating a
      strong need for the introduction of birth dose into the national immunisation
      system.

PMID- 24864632
TI  - Frequency of Streptococcus pneumonia and Haemophilus influenza in acute
      exacerbation of chronic obstructive airway disease and their sensitivity to
      levofloxacin.
AB  - OBJECTIVE: To determine the frequency of Streptococcus pneumoniae and Haemophilus
      influenzae in acute exacerbation of chronic obstructive pulmonary disease and
      their sensitivity to levofloxacin. METHODS: The cross-sectional study was
      conducted at the Department of Medicine, AbbasiShaheed Hospital, Karachi, between
      July 2009 and January 2010. Patients already diagnosed with chronic obstructive
      pulmonary disease and admitted with symptoms of acute exacerbation were included
      in the study and their sputum samples were sent for microbiological evaluation.
      SPSS 16 was used for statistical analysis. RESULTS: Of the total 105 patients in
      the study, 90 (85.17%) were males. Overall mean age at presentation was 62 +/-
      10.2 years. S. pneumoniae was isolated from sputum culture of 33 (31.4%)
      patients, while 13 (12.4%) patients showed growth of H. influenzae. Out of the 33
      sputum specimens of S. pneumoniae, 32 (97.0%) were sensitive to levofloxacin,
      while 1 (3.0%) was resistant. All the 13 isolates of H. influenzae were sensitive
      to levofloxacin. CONCLUSION: S. pneumoniae and H. influenzae are still the most
      prevalent organisms isolated in acute exacerbation of chronic obstructive
      pulmonary disease in our population. Levofloxacin is still considered a highly
      sensitive antibiotic against these common micro-organisms in our population, but
      S. pneumoniae has started developing resistance against levofloxacin. Therefore,
      intermittent surveillance regarding development of resistance pattern of common
      micro-organisms against commonly prescribed antibiotics is required.

PMID- 24864634
TI  - Experience of managing complicated diverticulitis of colon: a retrospective case
      series from South Asian country.
AB  - OBJECTIVE: To assess the morbidity and mortality associated with complicated
      diverticulitis in Pakistan. METHODS: The retrospective case series was conducted
      at an urban tertiary care university hospital of Karachi, Pakistan, comprising
      data from December 1989 to November 2010. International Classification of
      Diseases codes for diverticular disease and diverticulitis with abscess, fistula,
      stricture, bowel obstruction and perforation were obtained from the medical
      record department. SPSS 19 was used for statistical analysis. RESULTS: A total of
      60 (1.9%) cases with complicated diverticulitis were located from among 3170
      records reviewed. Mean age was 62.7 +/- 13 years with male-to-female ratio being
      36:24. In 37 (62%) patients, the diagnosis was established on computed tomography
      scan of the abdomen, followed by barium enema in 12 (20%) and colonoscopy in 11
      (18%). Post-operative morbidity was observed in 24 (40%) and 7 (16%) expired
      within 28 days of surgery. Post-operative intra-abdominal sepsis, wound
      dehiscence and incisional hernia were significantly associated with generalised
      peritonitis (p < 0.05), while admission to intensive care unit was associated
      with age over 60 years and faecal peritonitis. Post-operative mortality was
      significantly associated with high American Society of Anaesthesiologists-score
      III and IV and age above 60 years. CONCLUSION: Complicated diverticulitis carries
      significant morbidity and mortality in Pakistani population. Since the trend is
      on the rise, therefore we propose a prospective multi-centre cohort study to
      understand the spectrum of disease, management and identification of risk factors
      to achieve the best possible outcomes in patients with complicated
      diverticulitis.

PMID- 24864635
TI  - Comparison between tubularised incised plate urethroplasty and onlay island flap
      repair in mid and proximal penile hypospadias.
AB  - OBJECTIVES: To evaluate the surgical outcome of tubularised incised plate
      urethroplasty and onlay island flap repair for mid and proximal penile
      hypospadias. METHODS: The prospective study was conducted at the Bahawal Victoria
      Hospital, Bahawalpur from June 2011 to May 2013. A total of 60 patients with mid
      and proximal penile hypospadias in the age range of 02 to 06 years were included.
      Patients with hypospadias other than mid and proximal penile, with chordee and
      history of previous hypospadias repair were excluded. Patients were divided into
      two equal groups. Urethroplasty was done for group I and flap repair for group
      II. The follow-up period was 12-24 months. SPSS 16 was used for statistical
      analysis. RESULTS: The mean duration of surgery was 62 +/- 8.72 minutes for group
      I and 90 +/- 11.25 minutes for group II (p < 0.0001). In group I, only 03 (10.0%)
      patients had complications, while in group II, 09 (30.0%) patients developed
      complications (p = 0.02). Cosmetic results were also excellent in group I
      compared to group II. CONCLUSION: Tubularised incised plate urethroplasty was
      better and superior than onlay island flap repair in terms of less operative
      time, complication rate and satisfactory cosmetic results for mid and proximal
      penile hypospadias.

PMID- 24864636
TI  - CT scan in children with acute bacterial meningitis: experience from emergency
      department of a tertiary-care hospital in Karachi, Pakistan.
AB  - OBJECTIVE: To determine the role of computed tomography scan in children
      presenting to emergency department with symptoms and signs of suspected acute
      bacterial meningitis. METHODS: The retrospective analysis was done on children
      who were admitted through the Emergency Department at Aga Khan University
      Hospital, Karachi, from September 2009 to September 2011 with the diagnosis of
      acute bacterial meningitis. Information related to age, gender, presenting
      complaints, clinical signs and symptoms, computed tomography scan findings and
      final outcome of patients was gathered from the medical records. SPSS 19 was used
      for statistical analysis. RESULTS: A total of 192 patients were admitted with the
      relevant diagnosis. The male-female ratio was 2.3:1. Computed tomography scan was
      done in 114 (59.4%) patients. The scan was reported normal in 90 (78.94%)
      patients. However, cerebral oedema was found in 16 (14.03%) patients, cerebral
      infarct in 6(5.26%) and hydrocephalus in 2 (1.75%) patients. Overall, there were
      6 (3.1%) deaths. CONCLUSION: Comuted tomography scan may have a beneficial role
      in children with acute bacterial meningitis. However, further studies are
      required to use the scan as a routine investigation for such a diagnosis.

PMID- 24864637
TI  - Impact of scorpion stings on electrocardiographic changes and relationship with
      body oxidant and antioxidant status.
AB  - OBJECTIVE: To investigate electrocardiogram changes due to scorpion stings and
      association between oxidative stress index, body oxidant/antioxidant system and
      the electrocardiogram changes. METHODS: The study was conducted at the Faculty of
      Medicine, Gaziantep University, Turkey, between May 2009 and October 2010. It
      comprised 44 patients admitted to the emergency department for scorpion sting,
      and a control group of matched age and gender of 20 persons. Electrocardiograms
      were taken promptly in the most painful phases of the patients. Cardiac
      parametres were measured. Erythrocyte packages were prepared to detect
      toxin/antioxidant levels. SPSS 18 was used for statistical analysis. RESULTS: Of
      the 44 patients, 22 (50%) were male. Overall average age of the patients was
      45.22 +/- 17.99 years. None of the patients required intensive care and none of
      them had limb losses. Cardiac parametres of the patients in electrocardiogram
      were higher (p < 0.05). Difference between those with changed electrocardiogram
      and unchanged electrocardiogram in terms of the values of total antioxidant
      status, total oxidant status, and oxidative stress index, were not statistically
      significant (p > 0.05). CONCLUSION: Scorpion stings associated with
      electrocardiogram changes. The mechanism of this relationship is not related with
      the status of body oxidative stress index and body oxidant and antioxidant
      capacity. Some parametres warrant further study in terms of potential serious
      arrhythmias in scorpionism.

PMID- 24864638
TI  - Oral misoprostol versus oxytocin in the management of third stage of labour.
AB  - OBJECTIVES: To compare oral misoprostol versus intramuscular oxytocin in the
      management of third stage of labour. METHODS: The quasi-experimental study was
      conducted at the Obstetrics and Gynaecology Unit II, Civil Hospital, Karachi,
      from June 20 to December 19, 2006. A total of 70 patients diagnosed in active
      phase of labour who fulfilled the inclusion criteria were selected by non
      probability convenience sampling. These patients were divided into 2 groups of 35
      patients each, for Oxytocin (Group 1) and misoprostol (Group 2). Main and
      secondary outcome measures were analysed. SPSS 10 was used for statistical
      analysis. RESULTS: Average amount of blood loss(ml) was 267.14 +/- 140.35 with
      Oxytocin versus 302.86 +/- 160.4, with Misoprostol, this difference was
      statistically insignificant (p = 0.236). Average drop in haemoglobin
      concentration (g/dl) with Oxytocin was 1.55 +/- 0.38 vs 1.66 +/- 0.61 with
      Misoprostol (p = 0.684). Drop in haematocrit (%) was 4.18 +/- 0.64 with Oxytocin
      vs. 4.50 +/- 0.92 with Misoprostol (p = 0.133). There was also insignificant
      difference in duration of third stage of labour, between oxytocin and Misoprostol
      groups (5.37 +/- 2.20 vs. 5.23 +/- 2.46, p = 0.451) Shivering, in Misoprostol
      group occured in n = 11 (31.4%) vs n = 3 (8.6%) with Oxytocin (p = 0.017) and
      pyrexia in n = 6 (17.1%) with misoprostol vs n = 0, with oxytocin (p = 0.025)
      thus significantly higher in misoprostol group. CONCLUSION: There were no major
      differences in oral misoprostol and intramuscular oxytocin in the management of
      third stage of labour.

PMID- 24864639
TI  - Comparison of clinical effects of prilocaine, dexamethasone added to prilocaine
      and levobupivacaine on brachial plexus block.
AB  - OBJECTIVE: To determine whether the addition of 8 mg dexamethasone to axillary
      brachial plexus block would prolong the duration of sensory and motor block in
      patients undergoing hand and forearm surgery. METHODS: The prospective,
      randomised, double-blinded study was conducted at the Eskisehir Osmangazi
      University Medical School, Turkey, from October 2008 to December 2009. It
      comprised 45 American Society of Anaesthesiologists grade I and II patients under
      elective surgery of the hand and forearm. The patients were randomly divided into
      3 groups: 5 mg/kg of 2% prilocaine was applied to Group 1; 5 mg/kg of 2%
      prilocaine +8mg of dexamethasone (2 ml) was applied to Group 2; and 1.5 mg/kg
      0.5% levobupivacaine was applied to Group 3. Sensory and motor block onset time
      as well as the duration of motor and sensory block of those were monitored and
      recorded. SPSS 15 was used for statistical analysis. RESULTS: Of the 45 patients,
      27 (60%) were men and 18 (40%) were women. There was no significant difference
      among the groups in terms of demographic data. Based on the duration of motor and
      sensory block, similar periods of time in Group 1 and Group 2 were noted, whereas
      this period was statistically different and significantly longer in Group 3 (p <
      or = 0.001). There were no complications encountered. CONCLUSION: The addition of
      dexamethasone to prilocaine prolonged the duration of sensory and motor block. It
      could be used as an effective adjuvant agent. Levobupivacain could be a more
      appropriate local anaesthetic in postoperative analgesia and prolonged surgical
      procedures.

PMID- 24864640
TI  - Coeliac disease--clinical presentation and diagnosis by anti tissue
      transglutaminase antibodies titre in children.
AB  - OBJECTIVE: To study the spectrum of clinical presentation of coeliac disease and
      the role of IgA anti-tissue transglutaminase antibodies titer in the diagnosis
      and effect of gluten-free diet on such titers in children. METHODS: The
      prospective study was conducted in the paediatric department of Combined Military
      Hospital, Kharian from Sep 2011 to Sep 2012. Children of 1-12 years of age
      presenting with chronic diarrhoea, malnutrition and failure to thrive were
      included regardless of gender, socioeconomic status, ethnicity and geographical
      distribution. Anti-tissue transglutaminase angibodies titers were done on
      enrolment. Patients with levels more than 30 u/ml were enrolled. They were
      advised strict gluten-free diet for six months. These titers were repeated after
      six months to document the effect of gluten-free diet on these titers. Paediatric
      endoscopy and duodenal biopsy facilities were not available at the study site, so
      the response was monitored through titers. Data was analysed using SPSS-20.
      RESULTS: Out of 61 patients with IgA levels more than 10 u/ml, 52 (85.24%) were
      found to have a positive (> 30u/ml) anti-tissue transglutaminase antibodies
      titers with a mean value of 42.67 +/- 7.60 U/ml. These 52 patients were then put
      on a trial of gluten-free diet for six months after which significant reduction
      in titer was noticed, with a mean value of 13.25 +/- 2.59 U/ml. This reduction in
      titer was associated with marked clinical improvement and regression of symptoms.
      Frequency of different clinical features in descending order revealed that
      chronic diarrhoea, abdominal distension, iron deficiency anaemia, failure to
      thrive, pallor and rickets were present in 38 (73.1%), 30 (57.7%), 29 (55.8%), 29
      (53.8%), 28 (53.8%) patients respectively. CONCLUSION: Chronic diarrhoea, failure
      to thrive, pallor, abdominal distention and iron deficiency anaemia were common
      modes of presentation. The antibodies were strongly positive in most of the
      cases. All children showed significant improvement in clinical features and
      reduction in antibody titers after six-month trial of gluten free diet.

PMID- 24864641
TI  - Professional satisfaction of family physicians in Pakistan--results of a cross
      sectional postal survey.
AB  - OBJECTIVE: To assess the level of professional satisfaction amongst family
      physicians of Pakistan and to identify the factors associated with professional
      dissatisfaction. METHODS: The study was part of a larger national survey for
      "Status of PostgraduateTraining and Continuing Medical Education of Family
      Physicians in Pakistan" which was a cross-sectional, postal survey of family
      physicians conducted over 10 months between November 2009 and September 2010. The
      main outcome variables were professional satisfaction, as well as reasons for
      professional satisfaction and dissatisfaction. SPSS 17 was used for data
      analysis. Multivariable logistic regression was used to determine factors
      associated with professional dissatisfaction. RESULTS: Of the total 1200 survey
      forms distributed, 288 (24%) were received back. The mean age of the participants
      was 37 +/- 9 years with a range between 26 and 72 years. Of the total, 226
      (78.5%) were males. Overall, 213 (74%) family physicians were satisfied with
      their profession. The factors significantly associated with professional
      dissatisfaction included the participants opinion that they were not respected by
      the public (OR: 11.6, C.I: 1.9-71.5); as well as regretting being a doctor
      (OR:62.9, C.I: 8.4-469.8). CONCLUSIONS: Most of the family physicians had
      professional satisfaction, but a minority had regrets about being a doctor and
      were dissatisfied over how their profession affected their family life. Further
      research may be needed to study work-life balance amongst family physicians of
      Pakistan.

PMID- 24864642
TI  - Lipoprotein (A) in clinical practice.
AB  - Lipoprotein (a) is a strong and independent risk factor for atherosclerosis
      severity and a predictor of the risk of ischaemic heart disease and stroke. Many
      questions are still unanswered in relation to the clinical relevance of the
      scientific observations on Lp(a) and its application in the realms of
      cardiovascular prevention. Lp(a), a lipoprotein subtype, is linked to the Apo(a)
      gene located on chromosome 6q26-27 independently associated with increased risk
      of coronary artery disease (CAD). For this review, data sources from Cochrane,
      Pubmed, MEDLINE from 1960 till 2012 were analysed systematically. At least one
      off measurement of plasma Lp(a) was found to be indicated in those with premature
      coronary disease when no real causative factor was identified. Management seemed
      promising with PCSK9 I, apheresis, CETPI, dietary choices and ACEi. There was
      clear evidence that Lp(a) is a definite risk marker for atherosclerotic
      cardiovascular disease (CVD).

PMID- 24864643
TI  - Beyond the classroom, 'pro-active teaching methods--a must for today's CPD
      movement'.
AB  - Non-traditional teaching approaches are not recent innovations in the field of
      continuing medical and professional development; however, there is a lack of
      employing such methods in our context. The reasons could include lack of
      awareness, recognition and overlapping and adoption of these approaches,
      peculiarly academic detailing, by the pharmaceuticals. Nevertheless these methods
      have proven to be useful in changing physicians' behaviour and attitudes towards
      patient care and health safety. Moreover, it guides, promotes and derives the
      self-directedness of the physicians to acquire current knowledge, skills and
      generic attributes that are required for lifelong learning.

PMID- 24864644
TI  - Latex allergy on anaesthesiologist and anaesthesia managements: are the health
      workers high risk patients?
AB  - Anaphylaxis is defined as a severe, life threating, generalized or systemic
      hypersensitivity reaction. The most common agent involved in intraoperative
      anaphylactic reactions is muscle relaxant (61-70%); natural rubber latex (NRL) is
      the second most implicated agent and the incidence of latex-related anaphylactic
      reactions is increasing despite increasing awareness and preventive measures
      taken. Latex is a ubiquitous part of life today. Medical products which contain
      latex are present in our environment, especially in the hospital setting. This
      study focuses on our experience with two different anaesthetic techniques
      performed on the same patient who had latex hypersensitivity reaction and
      underwent surgery for myomectomy twice in 5 years. This case report aims to point
      out to latex hypersensitivity on health workers. The patient described had latex
      allergy and strategy of management during perioperative period is detailed.

PMID- 24864645
TI  - The Roberts syndrome: a case report of an infant with valvular aortic stenosis
      and mutation in ESCO2.
AB  - Roberts syndrome, which is inherited as an autosomal recessive group of
      disorders, is a rare syndrome characterized with symmetrical extremity defects,
      craniofacial abnormalities, and prenatal and postnatal growth retardation. Here,
      we present a case of Roberts Syndrome brought to the clinic with diarrhoea and
      multiple abnormalities, that had tetra phocomelia, growth and developmental
      retardation, abnormality of complete cleft lip-palate accompanied with Aortic
      stenosis and PDA, and in which cytogenetic analysis identified premature
      centromere separation. Mutation analysis of ESCO2 revealed a splice site mutation
      [c.1131+1G>A] in intron 6 in homozygous status in the patient and heterozygous
      status in the parents. Our case is the first Robert- Syndrome with valvular
      aortic stenosis in the literature, to the best of our knowledge.

PMID- 24864646
TI  - Gastrointestinal autonomic nerve tumour of jejunum presenting as a perforated
      mass.
AB  - Gastrointestinal autonomic nerve tumour (GANT) is a rare mesenchymal neoplasm of
      the gastrointestinal tract arising from the neural plexus of the intestinal wall.
      Herein, we present a 70-year-old male patient presenting with a clinical picture
      of acute abdomen. Examination of the specimen obtained from the small bowel by
      means of complete resection revealed a relatively soft submucosal mass measuring
      4.5 x 3 cm in size with spindle morphology and high mitotic activity (> 10
      mitoses per 50 high-power fields). The tumour cells were strong positive for c
      kit (CD117), S-100 protein and glial fibrillary acidic protein (GFAP), but did
      not harbour mutations in the c-kit and PDGFR genes. The diagnosis was based on
      light microscopy and immunohistochemical verification. We started tyrosine kinase
      inhibitor 400 mg/day. The patient is currently alive without metastasis at 28
      months postoperatively. He is under close follow-up and survival data of the
      patient will be presented in the later studies.

PMID- 24864647
TI  - A case of Budd-Chiari syndrome associated with alveolar echinococcosis.
AB  - Alveolar echinococcosis of the liver is caused by the tapeworm Echinococcus
      multilocularis. Budd-Chiari Syndrome (BCS) is a hepatic venous outflow tract
      obstruction and involves abdominal pain, hepatomegaly and high-gradient ascites.
      A low-gradient ascites in connection with the syndrome rarely occurs in case of
      alveolar echinococcosis of the liver. Here we report a 20-year-old man with the
      syndrome and low-gradient ascites due to a huge liver mass. Further diagnostic
      examination revealed alveolar echinococcosis of the liver. Diuretic agents and
      albendazole were used as palliative therapy in the case.

PMID- 24864648
TI  - Bilateral synchronous squamous cell tonsil carcinoma treated with
      chemoradiotherapy.
AB  - The incidence of numerous head and neck tumours is a known issue though bilateral
      synchronous tonsillar carcinoma reports are so uncommon that only 20 cases were
      found in a literature review. Most of these patients were treated with bilateral
      tonsillectomy followed by adjuvant radiotherapy. We report, to our knowledge, the
      first case of bilateral synchronous tonsillar squamous cell carcinoma treated
      only with chemoradiotherapy without tonsillectomy.

PMID- 24864649
TI  - Drug resistant neuroleptic malignant syndrome and the role of electroconvulsive
      therapy.
AB  - Neuroleptic malignant syndrome is considered as a rare but potentially fatal
      complication of neuroleptic medications e.g.,antipsychotics, sedatives and anti
      emetics. It is characterized by hyperthermia, muscle rigidity, an elevated
      creatine kinase level and autonomic instability. The syndrome often develops
      after the start of antipsychotic or a sudden increase in dosage of the
      neuroleptic medication or in states of dehydration. Treatment is mainly
      supportive and includes withdrawal of the neuroleptic medication and, possibly,
      administration of drugs such as dantrolene and bromocriptine. In rare cases where
      drugs treatment remains ineffective a trial of electroconvulsive therapy is being
      given. The case presented is a drug resistant case of Neuroleptic Malignant
      Syndrome where finally electroconvulsive therapy was effective.

PMID- 24864650
TI  - Alpha glucosidase inhibitors.
AB  - Alpha glucosidase inhibitors (AGIs) are a unique class of anti-diabetic drugs.
      Derived from bacteria, these oral drugs are enzyme inhibitors which do not have a
      pancreato -centred mechanism of action. Working to delay carbohydrate absorption
      in the gastrointestinal tract, they control postprandial hyperglycaemia and
      provide unquestioned cardiovascular benefit. Specially suited for a traditional
      Pakistani carbohydrate-rich diet, AGIs have been termed the 'untapped diamonds'
      of diabetology. The use of these oral antidiabetic drugs (OADs) that target
      pathophysiology in the early stages of type 2 diabetes, notably to reduce
      postprandial hyperglycaemia and hyperinsulinaemia will inevitably increase with
      time. This review describes the history of their development, mechanism of
      action, basic and clinical pharmacology, and suggests practical, evidence-based
      guidance for their optimal use.

PMID- 24864651
TI  - State of endovascular therapy for acute ischaemic stroke.

PMID- 24864652
TI  - Multiple flesh coloured nodules with unilateral segmental distribution.

PMID- 24864653
TI  - Road rage and road side accidents involvement in commercial vehicle drivers of
      Karachi.

PMID- 24864654
TI  - A patient with extended pneumonectomy for colorectal lung metastasis.

PMID- 24864655
TI  - Pseudohypoaldosteronism type-I: a rare cause of hyperkalemia in neonates.
AB  - Pseudohypoaldosteronism type I (PHA-I) is a rare disorder with only a few cases
      reported worldwide. It appears early in life with salt-wasting, failure to
      thrive, dehydration, hypotension, hyperkalaemia and metabolic acidosis. There is
      a resistance to aldosterone by the mineralocorticoid receptors. We describe one
      such case of a 14-day-old female neonate who presented with frequent episodes of
      dehydration, hyperkalaemia and hyponatraemia. On further workup, she proved to be
      a case of PHA-I. The aim of this report is to discuss the evaluation and to
      highlight the difficulties associated with the management of this rare disorder.

PMID- 24864656
TI  - Fears associated with human enhancement technologies: void or justified?

PMID- 24864657
TI  - Intestinal microbiota produced trimethylamine-N-oxide can increase the risk of
      cardiovascular disease.

PMID- 24864658
TI  - Obituary: Prof. Dr. Javed IIqbal Kazi.

PMID- 24865106
TI  - Development of stable isotope dilution assays for the quantitation of Amadori
      compounds in foods.
AB  - During thermal processing of foods, reducing carbohydrates and amino acids may
      form 1-amino-1-desoxyketoses named Amadori rearrangement products after the
      Italian chemist Mario Amadori. Although these compounds are transient
      intermediates of the Maillard reaction, they are often used as suitable markers
      to measure the extent of a thermal food processing, such as for spray-dried milk
      or dried fruits. Several methods are already available in the literature for
      their quantitation, but measurements are often done with external calibration
      without addressing losses during the workup procedure. To cope with this
      challenge, stable isotope dilution assays in combination with LC-MS/MS were
      developed for the glucose-derived Amadori products of the seven amino acids
      valine, leucine, isoleucine, phenylalanine, tyrosine, methionine, and histidine
      using the respective synthesized [(13)C6]-labeled isotopologues as internal
      standards. The quantitation of the analytes added to a model matrix showed a very
      good sensitivity with the lowest limits of detection for the Amadori compound of
      phenylalanine of 0.1 MUg/kg starch and 0.2 MUg/kg oil, respectively. Also, the
      standard deviation measured in, for example, wheat beer was only +/-2% for this
      analyte. Application of the method to several foods showed the highest
      concentrations of the Amadori product of valine in unroasted cocoa (342 mg/kg) as
      well as in dried bell pepper (3460 mg/kg). In agreement with literature data,
      drying of foods led to the formation of Amadori products, whereas they were
      degraded during roasting of, for example, coffee or cocoa. The study presents for
      the first time results on concentrations of the Amadori compounds of tyrosine and
      histidine in foods. 

PMID- 24865110
TI  - Method of symptom assessment influences cognitive, affective and somatic post
      concussion-like symptom base rates.
AB  - PRIMARY OBJECTIVE: To investigate whether assessment method influences the type
      of post-concussion-like symptoms. METHODS AND PROCEDURES: Participants were 73
      Australian undergraduate students (Mage = 24.14, SD = 8.84; 75.3% female) with no
      history of mild traumatic brain injury (mTBI). Participants reported symptoms
      experienced over the previous 2 weeks in response to an open-ended question (free
      report), mock interview and standardized checklist (British Columbia Post
      concussion Symptom Inventory; BC-PSI). MAIN OUTCOMES AND RESULTS: In the free
      report and checklist conditions, cognitive symptoms were reported significantly
      less frequently than affective (free report: p < 0.001; checklist: p < 0.001) or
      somatic symptoms (free report: p < 0.001; checklist: p = 0.004). However, in the
      mock structured interview condition, cognitive and somatic symptoms were reported
      significantly less frequently than affective symptoms (both p < 0.001). No
      participants reported at least one symptom from all three domains when assessed
      by free report, whereas most participants did so when symptoms were assessed by a
      mock structured interview (75%) or checklist (90%). CONCLUSIONS: Previous studies
      have shown that the method used to assess symptoms affects the number reported.
      This study shows that the assessment method also affects the type of reported
      symptoms.

PMID- 24865111
TI  - Formulation and evaluation of meloxicam oral disintegrating tablet with
      dissolution enhanced by combination of cyclodextrin and ion exchange resins.
AB  - CONTEXT: The bitter taste of drug is masked by the exchange of ionized drugs with
      counter ions of ion exchange resin, forming "resinate". Cyclodextrin reduces the
      unpleasant taste and enhances the drug solubility by encapsulating drug molecules
      into its central cavity. OBJECTIVE: Oral disintegrating tablets (ODTs) using the
      combination of ion exchange resin and cyclodextrin was developed, to mask the
      bitter taste and enhance drug dissolution. METHODS: Meloxicam (MX) was selected
      as a model drug. Formulations containing various forms of MX (free drug, MX
      loaded resin or resinate, complexes of MX and 2-hydroxypropyl-beta-cyclodextrin
      (HPbetaCD) or MX/HPbetaCD complexes, and a mixture of resinate and MX/HPbetaCD
      complexes) were made by direct compression. The ODTs were evaluated for weight
      variation, thickness, diameter, hardness, friability, disintegration time,
      wetting time, MX content, MX release, degree of bitter taste and stability.
      RESULTS AND DISCUSSION: The tablet hardness was ~3 kg/in(2), and the friability
      was <1%. Tablets formulated with resinate and the mixture of resinate and
      MX/HPbetaCD complexes disintegrated rapidly within 60 s, which is the acceptable
      limit for ODTs. These results were corresponded to the in vivo disintegration and
      wetting times. However, only tablets containing the mixture of resinate and
      MX/HPbetaCD complexes provided complete MX dissolution and successfully masked
      the bitter taste. In addition, this tablet was stable at least 6 months.
      CONCLUSIONS: The combination of ion exchange resin and cyclodextrin could be used
      in ODTs to mask the bitter taste and enhance the dissolution of drugs that are
      weakly soluble in water.

PMID- 24865112
TI  - Tools and approaches to ensure quality of vaccines throughout the cold chain.
AB  - The Expanded Program on Immunization was designed 40 years ago for two types of
      vaccines: those that are heat stable but freeze sensitive and those that are
      stable to freezing but heat labile. A cold chain was developed for transport and
      storage of such vaccines and established in all countries, despite limited access
      to resources and electricity in the poorest areas. However, cold chain problems
      occur in all countries. Recent changes to vaccines and vaccine handling include
      development and introduction of new vaccines with a wide range of
      characteristics, improvement of heat stability of several basic vaccines,
      observation of vaccine freezing as a real threat, development of regulatory
      pathways for both vaccine development and the supply chain, and emergence of new
      temperature monitoring devices that can pinpoint and avoid problems. With such
      tools, public health groups have now encouraged development of vaccines labeled
      for use in flexible cold chains and these tools should be considered for future
      systems. 

PMID- 24865115
TI  - Effects of olive leaf polyphenols on male mouse brain NGF, BDNF and their
      receptors TrkA, TrkB and p75.
AB  - In this study, we evaluated, in the mouse, the effects of 20 mg/kg i.p. daily
      administration for 15 consecutive days of a blend of polyphenols, containing
      mostly oleuropein, extracted from the olive leaves (Olea europaea) on brain nerve
      growth factor (NGF) and brain-derived neurotrophic factor (BDNF) and on the
      expression of their receptors, TrkA, TrkB and p75. Polyphenols decreased the
      levels of reduced glutathione (GSH) and increased the levels of NGF and BDNF in
      the serum. In the brain, we found decreased levels of NGF and BDNF in the
      hippocampus and striatum but elevated levels of NGF in the olfactory lobes and
      hypothalamus and again BDNF potentiation in the olfactory lobes. No changes in
      TrkA, TrkB and p75 expression were observed. In conclusion, olive polyphenols may
      not only elicit an activation of the rodent olfactory system by increasing the
      levels of NGF and BDNF but also be stressing for the animal by reducing both the
      levels of hippocampal NGF/BDNF and serum GSH and increasing serum levels of NGF
      and BDNF. 

PMID- 24865116
TI  - Incidence, diagnosis and pathophysiology of amniotic fluid embolism.
AB  - Amniotic fluid embolism (AFE) is a rare clinical entity, sometimes fatal. A
      review was conducted to describe the frequency, diagnosis and pathophysiology of
      AFE. The reported incidences ranged from 1.9 cases per 100,000 maternities (UK)
      to 6.1 per 100,000 maternities (Australia), which can vary considerably,
      depending on the period, region of study and the definition. Although the
      development of amniotic fluid-specific markers would have an impact on early
      diagnosis, definition of AFE based on these markers is not widely accepted. To
      date, immunological mechanisms, amniotic fluid-dependent anaphylactic reaction
      and complement activation, have been proposed as potential pathogenetic and
      pathophysiological mechanisms. Immune cell activation induced through complement
      activation may be associated with the mechanism that immediately initiates
      maternal death, only in susceptible individuals. This review will focus on
      advances in the field of AFE biology and discuss the prevalence, diagnosis and
      pathophysiology of AFE.

PMID- 24865108
TI  - Positron emission tomography image-guided drug delivery: current status and
      future perspectives.
AB  - Positron emission tomography (PET) is an important modality in the field of
      molecular imaging, which is gradually impacting patient care by providing safe,
      fast, and reliable techniques that help to alter the course of patient care by
      revealing invasive, de facto procedures to be unnecessary or rendering them
      obsolete. Also, PET provides a key connection between the molecular mechanisms
      involved in the pathophysiology of disease and the according targeted therapies.
      Recently, PET imaging is also gaining ground in the field of drug delivery.
      Current drug delivery research is focused on developing novel drug delivery
      systems with emphasis on precise targeting, accurate dose delivery, and minimal
      toxicity in order to achieve maximum therapeutic efficacy. At the intersection
      between PET imaging and controlled drug delivery, interest has grown in combining
      both these paradigms into clinically effective formulations. PET image-guided
      drug delivery has great potential to revolutionize patient care by in vivo
      assessment of drug biodistribution and accumulation at the target site and real
      time monitoring of the therapeutic outcome. The expected end point of this
      approach is to provide fundamental support for the optimization of innovative
      diagnostic and therapeutic strategies that could contribute to emerging concepts
      in the field of "personalized medicine". This review focuses on the recent
      developments in PET image-guided drug delivery and discusses intriguing
      opportunities for future development. The preclinical data reported to date are
      quite promising, and it is evident that such strategies in cancer management hold
      promise for clinically translatable advances that can positively impact the
      overall diagnostic and therapeutic processes and result in enhanced quality of
      life for cancer patients. 

PMID- 24865119
TI  - Socioeconomic inequalities in cancer survival: a population-based study of adult
      patients diagnosed in Osaka, Japan, during the period 1993-2004.
AB  - BACKGROUND: Long-term recession of the Japanese economy during the 1990s led to
      growing social inequalities whilst health inequalities also appeared. The 2007
      National Cancer Control Program of Japan targeted "equalisation of cancer medical
      services", but the system to monitor health inequalities was still inadequate. We
      aimed to measure socioeconomic inequalities in cancer survival in Japan. MATERIAL
      AND METHODS: We analysed 13 common invasive, primary, malignant tumours diagnosed
      from 1993 to 2004 and registered by the population-based Cancer Registry of Osaka
      Prefecture. An ecological socioeconomic deprivation index based on small area
      statistics, divided into quintile groups, was linked to patients according to
      their area of residence at the time of diagnosis. We estimated one-, five-year
      and conditional five-year net survival by sex, period of diagnosis (1993
      1996/1997-2000/2001-2004) and deprivation group. Changes in survival over time,
      deprivation gap in survival, and change in deprivation gap were estimated at one
      and five years after diagnosis using variance-weighted least square regression.
      RESULTS: The deprivation gap in one-year net survival was narrower than in five
      year net survival and conditional five-year survival. During the study period,
      there was no change in deprivation gap, except for reductions for pancreas (men)
      and stomach (women), and an increase for lung (men) in one-year survival. We
      observed a linear association between level of survival and deprivation gap at
      five years and conditional five years, but no association at one-year survival.
      CONCLUSION: A wide deprivation gap in survival was observed in most of the adult,
      solid, malignant tumours, within the universal healthcare system in Japan.
      Overall, cancer survival improved in Osaka without any widening of inequalities
      in cancer survival in 1993-2004, shortly after the long-term economic recession
      and deep modifications in the social and work environments in Japan. The longer
      term impact of the recession on inequalities in cancer survival needs to be
      monitored using population-based cancer registry data.

PMID- 24865118
TI  - The response to vaccination against influenza A(H1N1) 2009, seasonal influenza
      and Streptococcus pneumoniae in adult outpatients with ongoing treatment for
      cancer with and without rituximab.
AB  - It is debated whether cancer patients treated with chemotherapy can mount an
      adequate response to vaccination. MATERIAL AND METHODS: Ninety-six adult
      outpatients with cancer, who were undergoing chemotherapy and/or monoclonal
      antibody, tyrosine kinase inhibitor, irradiation or corticosteroid treatments,
      were studied. Two doses of the pandemic influenza A(H1N1)/09 AS03-adjuvanted
      split virion vaccine, one dose of the seasonal influenza vaccine and one dose of
      the 23-valent pneumococcal polysaccharide vaccine were given. Serum
      haemagglutination inhibition (HI) assays were used to determine antibody titres
      against the influenza strains. For the pneumococcal vaccine 14 different serotype
      specific anti-capsular antibodies were measured by bead assay xMAP((r)). RESULTS:
      Patients treated with rituximab did not respond to vaccination. For patients
      without rituximab treatment 4% had putatively protective antibodies before
      vaccination (HI >= 40) to the pandemic-like strain A/California7/2009HINI. After
      the first and second dose of vaccine, seroprotection rates (SPR) were 62% and
      87%, and seroconversion rates (SCR) 62% and 84%, respectively. Before seasonal
      flu vaccination SPR against influenza A/Brisbane/59/2007H1N1 and
      A/Uruguay/10/2007H3N2 were 19% and 17%, respectively. After vaccination, SPR were
      70% and 59% and SCR 42% and 50%, respectively. For the pneumococcal vaccine
      protective antibodies were found to 40% of the 14 strains before and to 68% after
      vaccination. The mean response to pneumococcal vaccination was to 44% of the 14
      serotypes. A response to at least 50% of the 14 serotypes was found in 49% of the
      patients. No serious adverse events were reported. CONCLUSION: A substantial
      number of adult cancer patients with ongoing chemotherapy treatment could mount
      an adequate serological response to influenza and pneumococcal vaccination
      without severe adverse events. Thus, vaccination should be recommended.
      Adjuvanted vaccines may improve the vaccine response among this patient group.
      Patients recently treated with rituximab do not respond to vaccination.

PMID- 24865120
TI  - Home-based DIR/Floortime intervention program for preschool children with autism
      spectrum disorders: preliminary findings.
AB  - Improving parent-child interaction and play are important outcomes for children
      with autism spectrum disorder (ASD). Play is the primary occupation of children.
      In this pilot study conducted in Taiwan, we investigated the effects of the
      developmental, individual difference, and relationship-based (DIR)/Floortime home
      based intervention program on social interaction and adaptive functioning of
      children with ASD. The participants were 11 children with ASD, ages from 45-69
      months, and their mothers. Mothers were instructed the principles of the approach
      by an occupational therapist. All 11 children and their mothers completed the 10
      week home-based intervention program, undergoing an average of 109.7 hr of
      intervention. Children made significant changes in mean scores for emotional
      functioning, communication, and daily living skills. Moreover, the mothers
      perceived positive changes in their parent-child interactions. The findings of
      this pilot study contribute to knowledge regarding the effects of home-based
      DIR/Floortime intervention program on increasing the social interaction and
      adaptive behaviors of children with ASD in Taiwan.

PMID- 24865121
TI  - Children's perspective on their right to participate in decision-making according
      to the United Nations Convention on the Rights of the Child article 12.
AB  - ABSTRACT Aims: According to the United Nations Convention on the Rights of the
      Child article 12, children have a right to express their views. However,
      knowledge on how children with a disability perceive this right and the extent to
      which they would like to access this right is unclear. The aim of this study was
      to describe and capture the meaning of children's perspective on their right to
      participate in decision-making together with the children's lived experiences in
      pediatric rehabilitation. Methods: A phenomenological hermeneutical research
      design was applied for gathering the thoughts and lived experiences of seven
      children with different disabilities through individual interviews and
      observations. Results: The children expressed satisfaction with participation
      being limited to less important decisions. This may be understood as lack of
      experience with participation in decision-making or an inherent wish of becoming
      like peers and therefore viewing therapists as experts of a normalization
      process. Conclusions: Health care professionals should consider informing the
      child of the possibility of decision-making and for negotiating power-sharing and
      responsibility concerning decisions in pediatric rehabilitation.

PMID- 24865122
TI  - The impact of childhood traumas, depressive and anxiety symptoms on the
      relationship between borderline personality features and symptoms of adult
      attention deficit hyperactivity disorder in Turkish university students.
AB  - BACKGROUND: Previous studies reported that there is a significant association
      between attention deficit hyperactivity disorder (ADHD) in childhood and
      borderline personality disorder (BPD) in adulthood. AIM: The aim of this study is
      to investigate the relationship of borderline personality features (BPF) and ADHD
      symptoms while controlling the effect of childhood traumas, symptoms of
      depression and anxiety in adulthood on this relationship in Turkish university
      students. METHODS: A total of 271 Turkish university students participated in
      this study. The students were assessed through the Turkish version of the
      Borderline Personality Inventory (BPI), the Adult ADHD Self-Report Scale (ASRS),
      the Childhood Trauma Questionnaire (CTQ-28), the Beck Depression Inventory (BDI)
      and the Beck Anxiety Inventory (BAI). RESULTS: Correlation analyses have revealed
      that severity of BPF is related with adult ADHD symptoms, emotional, physical
      abuse and depression scores. Hierarchical regression analysis has indicated that
      depressive symptoms, emotional and physical abuse and the severity of ADHD
      symptoms are the predictors for severity of BPF. CONCLUSIONS: Findings of the
      present study suggests that clinicians must carefully evaluate these variables
      and the relationship between them to understand BPF and ADHD symptoms in
      university students better. Together with depressive symptoms, emotional and
      physical abuse may play a mediator role on this relationship. Further studies are
      needed to evaluate causal relationship between these variables in both clinical
      and non-clinical populations.

PMID- 24865123
TI  - Evaluation of procalcitonin as a marker to predict antibiotic response in adult
      patients with acute appendicitis: a prospective observational study.
AB  - BACKGROUND: The aim of the study was to investigate the value of serum
      procalcitonin (PCT) as a predictor of early antibiotic treatment response in
      patients with acute appendicitis. Procalcitonin is a biochemical marker that
      increases rapidly in cases of bacterial infection and sepsis; however, the
      benefit of PCT as a diagnostic tool in acute appendicitis has not been confirmed.
      METHODS: Observations of PCT dynamics were conducted as part of a prospective
      clinical trial at Sahlgrenska University Hospital between May 2009 and February
      2010 on adult patients with acute appendicitis treated with antibiotics as first
      line therapy. Procalcitonin, C-reactive protein (CRP), and white blood cell count
      (WBC) were measured before administration of antibiotics and subsequently between
      4-24 h following treatment. RESULTS: Three hundred sixteen patients were included
      in the study. Almost 80% recovered on antibiotics without the need of surgery.
      Serum PCT concentrations before initiation of antibiotic therapy and during
      treatment did not differ significantly between antibiotic responders and non
      responders (p<0.94). However, differences were observed for CRP (p<0.04) and WBC
      (p<0.001), with a trend for body temperature (p<0.06). CONCLUSION: Procalcitonin
      has limited additional value, compared with standard laboratory tests as CRP,
      WBC, and body temperature to predict antibiotic treatment response in adult
      patients with acute appendicitis.

PMID- 24865128
TI  - Proliferation patterns in a pig model of AV fistula stenosis: can we translate
      biology into novel therapies?
AB  - Arteriovenous fistula (AVF) stenosis remains an important cause of AVF maturation
      failure for which there are currently no effective therapies. To understand the
      mechanisms involved, we have examined the pattern of cellular proliferation at
      different time points in a pig model of AVF stenosis. Immunohistochemical
      analysis of cellular proliferation was performed at 2, 7, 28, and 42 days. The
      distribution of cellular proliferation within the different layers of the vessel
      wall was also studied. An ANOVA analysis was used to identify differences between
      the magnitude of cellular proliferation at different time points and within
      different layers of the vessel wall. Adventitial proliferation occurred at 2 days
      and declined over time. Intimal and medial proliferation peaked at 7 days and
      then decreased over time. There was minimal proliferation in all three layers at
      the 28- and 42-day time points. An important finding was the presence of active
      myofibroblast proliferation within "neointimal buds" at the 7-day time point.
      Results suggest that there could be early adventitial activation, followed by a
      passage of these cells into the medial and intimal layers. These suggest that the
      application of perivascular antiproliferative (adventitial) therapies at the time
      of surgery could potentially reduce AVF maturation failure. 

PMID- 24865127
TI  - Dimensions of manic symptoms in youth: psychosocial impairment and cognitive
      performance in the IMAGEN sample.
AB  - BACKGROUND: It has been reported that mania may be associated with superior
      cognitive performance. In this study, we test the hypothesis that manic symptoms
      in youth separate along two correlated dimensions and that a symptom
      constellation of high energy and cheerfulness is associated with superior
      cognitive performance. METHOD: We studied 1755 participants of the IMAGEN study,
      of average age 14.4 years (SD = 0.43), 50.7% girls. Manic symptoms were assessed
      using the Development and Wellbeing Assessment by interviewing parents and young
      people. Cognition was assessed using the Wechsler Intelligence Scale For Children
      (WISC-IV) and a response inhibition task. RESULTS: Manic symptoms in youth formed
      two correlated dimensions: one termed exuberance, characterized by high energy
      and cheerfulness and one of undercontrol with distractibility, irritability and
      risk-taking behavior. Only the undercontrol, but not the exuberant dimension, was
      independently associated with measures of psychosocial impairment. In
      multivariate regression models, the exuberant, but not the undercontrolled,
      dimension was positively and significantly associated with verbal IQ by both
      parent- and self-report; conversely, the undercontrolled, but not the exuberant,
      dimension was associated with poor performance in a response inhibition task.
      CONCLUSIONS: Our findings suggest that manic symptoms in youth may form
      dimensions with distinct correlates. The results are in keeping with previous
      findings about superior performance associated with mania. Further research is
      required to study etiological differences between these symptom dimensions and
      their implications for clinical practice.

PMID- 24865129
TI  - Approximal caries increment in adolescents in a low caries prevalence area in
      Sweden after a 3.5-year school-based fluoride varnish programme with Bifluorid 12
      and Duraphat.
AB  - OBJECTIVES: To evaluate approximal caries increment among 12- to 16-year-olds in
      a low caries prevalence area in Sweden after a 3.5-year school-based fluoride (F)
      varnish programme with Bifluorid 12 and Duraphat. METHODS: The design was a RCT
      study with 1365 adolescents, divided into following four groups: Group 1
      Bifluorid 12 two applications/year; Group 2 Duraphat two applications/year; Group
      3 Bifluorid 12 four applications/year and Group 4 no F varnish at school. 1143
      children (84%) completed the study. Approximal caries was registered on bitewing
      radiographs. RESULTS: There were no statistically significant differences in
      caries prevalence among the groups either at baseline or after 3.5 years . The
      caries increment for Group 1 was 1.34 +/- 2.99 (mean +/- SD), 1.24 +/- 2.84 for
      Group 2, 1.07 +/- 2.66 for Group 3 and 1.25 +/- 2.75 for Group 4, with no
      statically significant differences either between Bifluorid 12 and Duraphat with
      the same frequency of F varnish applications or between the F groups and the
      control group. CONCLUSIONS: In an area with low caries prevalence in Sweden, the
      supplementary caries-preventive effect of school-based F varnish applications, to
      regular use of F toothpaste at home and to regular caries prevention given at the
      Public Dental Clinics, appears to be nonsignificant regarding approximal caries
      increment.

PMID- 24865131
TI  - Short-term effects of milking frequency on milk yield, milk composition, somatic
      cell count and milk protein profile in dairy goats.
AB  - Goats in Canary Islands are milked once a day by tradition, but in most countries
      with high technology on farms, goats are milked twice a day, which is known to
      improve milk yield. Therefore it is important to know whether the increase of
      milking frequency can improve the production without impairing milk quality. The
      objective of this study was to investigate the short term effects of three
      milking frequencies on milk yield, milk composition, somatic cell count (SCC) and
      milk protein profile in dairy goats traditionally milked once a day. Twelve
      Majorera goats in early lactation (48+/-4 d in milk) were used. During a 5-week
      period, goats were milked once a day (X1) in weeks 1 and 5, twice a day (X2) in
      weeks 2 and 4, and three times a day (X3) in week 3. Milk recording and sampling
      were done on the last day of each experimental week. Milk yield increased by 26%
      from X1 to X2. No differences were obtained when goats were switched from X2 to
      X3, and from X3 to X2. The goats recovered the production level when they
      returned to X1. Different patterns of changes in the milk constituents due to the
      milking frequency effect were observed. Fat percentage increased when switched
      from X1 to X2, then decreased from X2 to X3, and from X3 to X2, whereas it did
      not show significant differences from X2 to X1. Milking frequency did not affect
      the protein and lactose percentages. SCC values were unaffected when goats were
      milked X1, X2 and X3, but then they increased slightly when milking frequency was
      returned to X2 and X1. Finally, quantitative analysis showed an increase in
      intensities of milk protein bands from X1 to X2, but the intensities of casein
      bands (alpha(S1)-CN, alpha(S2)-CN, beta-CN, kappa-CN) and major whey proteins
      (alpha-La, beta-Lg) decreased from X2 to X3.

PMID- 24865132
TI  - Safety and efficacy of the dipeptidyl peptidase-4 inhibitor linagliptin in
      elderly patients with type 2 diabetes: a comprehensive analysis of data from 1331
      individuals aged >= 65 years.
AB  - AIMS: To investigate individual patient data from a comprehensive trials
      programme to evaluate the safety and efficacy of the dipeptidyl peptidase-4 (DPP
      4) inhibitor linagliptin across a range of glucose-lowering regimens in a large
      elderly population with type 2 diabetes mellitus (T2DM). METHODS: Data were
      pooled from individuals aged >= 65 years, who participated in seven phase III,
      placebo-controlled clinical trials of linagliptin (24-52 weeks). Safety was
      assessed by incidence and severity of adverse events (AEs) with a focus on
      hypoglycaemia. The primary efficacy endpoint was change in glycated haemoglobin
      (HbA1c). RESULTS: In total, 841 subjects received linagliptin 5 mg once a day and
      490 received placebo. At baseline, the population had a mean +/- s.d. age of 71.0
      +/- 4.6 years and a mean HbA1c concentration of 8.0 +/- 0.8%; 63.5% of subjects
      received >= 2 antidiabetes drugs. Overall AEs and drug-related AEs were
      experienced by similar proportions of patients (linagliptin 71.3, placebo 73.3;
      linagliptin 18.1, placebo 19.8%, respectively). The incidence of investigator
      reported hypoglycaemia was 21.4% with linagliptin and 25.7% with placebo. Severe
      hypoglycaemic events were rare and there were fewer in the linagliptin group (1.0
      vs. 1.8%). At week 24, the placebo-corrected adjusted mean +/- s.e. reduction in
      HbA1c with linagliptin was -0.62 +/- 0.06% (95% CI: -0.73, -0.51). CONCLUSIONS:
      Data from this large cohort show that linagliptin is a well-tolerated and
      efficacious therapy for elderly patients with T2DM. Treatment with linagliptin
      may support individualized treatment goals, while effectively managing the risk
      of hypoglycaemia or drug-related side effects.

PMID- 24865133
TI  - Hospice and palliation in the English-speaking Caribbean.
AB  - This article presents empirical data on the limited availability of hospice and
      palliative care to the 6 million people of the English-speaking Caribbean. Ten of
      the 13 nations therein responded to a survey and reported employing a total of 6
      hospice or palliative specialists, and having a total of 15 related facilities.
      The evolving socioeconomic and cultural context in these nations bears on the
      availability of such care, and on the willingness to report, assess, and
      prioritize pain, and to prescribe opiates for pain. Socioeconomics and culture
      also impinge on what medications and modalities of care are routinely available
      for pain or other conditions and can challenge professionalism, empathy, and
      responsiveness to patients' unrelieved pain. Although all respondents report
      having a protocol for pain management, hospice, or end-of-life care, their annual
      medical use of opiates is well below the global mean. The International Narcotics
      Control Board (INCB), which monitors such use, encourages Caribbean and other low
      and middle-income countries to increase their use of opiates to treat pain, and
      to overcome both unfounded fears of addiction and overly restrictive
      interpretation of related laws and regulations. Contextual considerations like
      those described here are important to the success of policies and capacity
      building programs aiming to increase access to hospice and palliation, and
      perhaps to improving other aspects of health and healthcare. Exploring and
      responding to the realities of socioeconomic and cultural conditions will enhance
      public and policy dialogue and improve the design of interventions to increase
      access to palliative and hospice care. Improving access to palliative and hospice
      care in the Caribbean demonstrates beneficence and helps to fulfill human rights
      conventions.

PMID- 24865134
TI  - Relationship between plasma chemerin levels and disease severity in COPD
      patients.
AB  - BACKGROUND AND AIMS: Chronic inflammation of the lung is a characteristic finding
      in chronic obstructive pulmonary disease (COPD). The protein chemerin has been
      identified in inflammatory fluid and in inflamed tissues. This study aimed to
      determine the association between serum chemerin levels and the severity of COPD.
      METHODS: Forty-three COPD patients and 38 healthy subjects were enrolled in this
      study. Fasting plasma samples were obtained from the patient and the control
      group. Serum chemerin levels were measured using a commercial enzyme-linked
      immunosorbent assay. C-reactive protein levels, the erythrocyte sedimentation
      rate, and fibrinogen analysis were used to assess the inflammation status of the
      patients. Spirometric measurements with reversibility testing were performed in
      all the subjects. RESULTS: Serum chemerin levels were significantly elevated in
      the COPD patients (6.44 +/- 0.52 vs 5.22 +/- 0.59; P < 0.001). A Mann-Whitney U
      test revealed that the serum chemerin levels of stage 2 COPD patients were higher
      than those of stage 1 and 3 COPD patients (P = 0.651). Cigarette smoking and
      plasma chemerin relation was also understudied; however, there was no significant
      relationship between current smokers and ex-smokers (P > 0.05). Pearson's
      correlation analysis indicated that serum chemerin levels were positively
      correlated only with total cholesterol (T. cholesterol) (P < 0.05, r = 0.382). In
      the linear regression analysis, chemerin levels were associated with age (beta =
      0.321), triglycerides (beta = 0.299) and T. cholesterol (beta = 0.555).
      CONCLUSION: Our study points to a relation between plasma chemerin levels and
      COPD. Larger patient groups are needed to verify the role of chemerin in the
      severity of COPD.

PMID- 24865135
TI  - Proteomic analyses of soybean root tips during germination.
AB  - Plant root systems form complex networks with the surrounding soil environment
      and are controlled by both internal and external factors. To better understand
      the function of root tips of soybean during germination, three proteomic
      techniques were used to analyze the protein profiles of root tip cells. Proteins
      were extracted from the root tips of 4-day-old soybean seedlings and analyzed
      using two-dimensional (2D) gel electrophoresis-based proteomics, SDS-gel based
      proteomics, and gel-free proteomics techniques. A total of 121, 862, and 341
      proteins were identified in root tips using the 2D gel-based, SDS gel-based, and
      gel-free proteomic techniques, respectively. The proteins identified by 2D gel
      based proteomic analysis were predominantly localized in the cytoplasm, whereas
      nuclear-localized proteins were most commonly identified by the SDS gel-based and
      gel-free proteomics techniques. Of the 862 proteins identified in the SDS gel
      based proteomic analysis, 190 were protein synthesis-related proteins.
      Furthermore, 24 proteins identified using the 2D-gel based proteomic technique
      shifted between acidic and basic isoelectric points, and 2 proteins, heat shock
      protein 70.2 and AAA-type ATPase, displayed two different molecular weights at
      the same isoelectric point. Taken together, these results suggest that a number
      of proteins related to protein synthesis and modification are activated in the
      root tips of soybean seedlings during germination.

PMID- 24865140
TI  - NOS3 polymorphism, lung function, and exposure in swine operations: results of 2
      studies.

PMID- 24865141
TI  - Nesting and pollen preference of Osmia lignaria lignaria (Hymenoptera:
      Megachilidae) in Virginia and North Carolina orchards.
AB  - Cavity-nesting megachilid bees in the genus Osmia, found throughout the
      Palearctic and Nearctic regions, are good candidates for domestication. In North
      America, Osmia lignaria Say has been reported to be an excellent pollinator of
      tree fruit and is currently being developed for commercial use in orchards. This
      is largely because of research over several decades with the western subspecies
      of this bee, Osmia lignaria propinqua Cresson, in western orchards. The behavior
      of the eastern subspecies, O. lignaria lignaria Say, in eastern orchards has not
      previously been reported. This study evaluated the nesting activity and pollen
      preference of a population of the eastern subspecies in five orchards in the
      foothills and piedmont regions of North Carolina and Virginia over a 2-yr period.
      Apple was present in all orchards and all were bordered by hardwood forest.
      Shelters were placed both within orchards and the forest border. Emergence dates,
      nest construction, and orchard bloom were monitored weekly. Bee populations
      increased by 2-3 times annually at most orchards. Pollen species comprising nest
      provisions from 720 individual nest cells were identified and quantified using
      scanning electron microscopy. The greatest amount of pollen (46-82%) was that of
      a small understory tree, Eastern redbud (Cercis canadensis L.), at all orchard
      sites where these trees were present nearby. The quantity of orchard pollen was
      relatively low, <20% at full apple bloom, except for one orchard (53%) without
      nearby redbud. O. lignaria lignaria appears to prefer Eastern redbud pollen over
      orchard pollen. 

PMID- 24865145
TI  - Beyond the material grave: Life Cycle Impact Assessment of leaching from
      secondary materials in road and earth constructions.
AB  - In industrialized countries, large amounts of mineral wastes are produced. They
      are re-used in various ways, particularly in road and earth constructions,
      substituting primary resources such as gravel. However, they may also contain
      pollutants, such as heavy metals, which may be leached to the groundwater. The
      toxic impacts of these emissions are so far often neglected within Life Cycle
      Assessments (LCA) of products or waste treatment services and thus, potentially
      large environmental impacts are currently missed. This study aims at closing this
      gap by assessing the ecotoxic impacts of heavy metal leaching from industrial
      mineral wastes in road and earth constructions. The flows of metals such as Sb,
      As, Pb, Cd, Cr, Cu, Mo, Ni, V and Zn originating from three typical constructions
      to the environment are quantified, their fate in the environment is assessed and
      potential ecotoxic effects evaluated. For our reference country, Germany, the
      industrial wastes that are applied as Granular Secondary Construction Material
      (GSCM) carry more than 45,000 t of diverse heavy metals per year. Depending on
      the material quality and construction type applied, up to 150 t of heavy metals
      may leach to the environment within the first 100 years after construction. Heavy
      metal retardation in subsoil can potentially reduce the fate to groundwater by up
      to 100%. One major challenge of integrating leaching from constructions into
      macro-scale LCA frameworks is the high variability in micro-scale technical and
      geographical factors, such as material qualities, construction types and soil
      types. In our work, we consider a broad range of parameter values in the modeling
      of leaching and fate. This allows distinguishing between the impacts of various
      road constructions, as well as sites with different soil properties. The findings
      of this study promote the quantitative consideration of environmental impacts of
      long-term leaching in Life Cycle Assessment, complementing site-specific risk
      assessment, for the design of waste management strategies, particularly in the
      construction sector.

PMID- 24865143
TI  - Evaluation of aortic stenosis severity using 4D flow jet shear layer detection
      for the measurement of valve effective orifice area.
AB  - AIMS: The objective of this study was to evaluate the potential of 4D flow MRI to
      assess valve effective orifice area (EOA) in patients with aortic stenosis as
      determined by the jet shear layer detection (JSLD) method. METHODS AND RESULTS:
      An in-vitro stenosis phantom was used for validation and in-vivo imaging was
      performed in 10 healthy controls and 40 patients with aortic stenosis. EOA was
      calculated by the JSLD method using standard 2D phase contrast MRI (PC-MRI) and
      4D flow MRI measurements (EOAJSLD-2D and EOAJSLD-4D, respectively). As a
      reference standard, the continuity equation was used to calculate EOA (EOACE)
      with the 2D PC-MRI velocity field and compared to the EOAJSLD measurements. The
      in-vitro results exhibited excellent agreement between flow theory
      (EOA=0.78cm(2)) and experimental measurement (EOAJSLD-4D=0.78+/-0.01cm(2)) for
      peak velocities ranging from 0.9 to 3.7m/s. In-vivo results showed good
      correlation and agreement between EOAJSLD-2D and EOACE (r=0.91, p<0.001; bias: 
      0.01+/-0.38cm(2); agreement limits: 0.75 to -0.77cm(2)), and between EOAJSLD-4D
      and EOACE (r=0.95, p<0.001; bias: -0.09+/-0.26cm(2); limits: 0.43 to -0.62cm(2)).
      CONCLUSION: This study demonstrates the feasibility of measuring EOAJSLD using 4D
      flow MRI. The technique allows for optimization of the EOA measurement position
      by visualizing the 3D vena contracta, and avoids potential sources of EOACE
      measurement variability.

PMID- 24865150
TI  - Targeting the alpha7 nicotinic acetylcholine receptor to prevent progressive
      dementia and improve cognition in adults with Down's syndrome.
AB  - As persons with Down's syndrome (DS) age into the third decade and beyond, they
      develop Alzheimer's disease (AD)-like histopathological changes in brain and may
      manifest progressive worsening of adaptive functions. Increasingly, persons with
      DS have near-normal to normal life spans; thus, it has become a therapeutic
      imperative to preserve adaptive functions and ability to live as independently as
      possible in the least restrictive environment throughout adulthood. Data suggest
      that these histopathological changes and worsening adaptive functions result, at
      least in part, from the binding of the amyloidogenic Abeta1-42 peptide to alpha7
      nicotinic acetylcholine receptors (alpha7nAChRs) on the surface of neurons, which
      can lead to the internalization of the tightly-bound complex and cell lysis.
      Pharmacotherapeutic targeting of the alpha7nAChR may inhibit the creation of the
      Abeta1-42-alpha7nAChR complex, which has been observed both intraneuronally and
      as a component of the amyloid plaque seen in AD. Additionally, selective
      alpha7nAChR agonists may improve memory and cognition independently of their
      potential ability to attenuate the cytotoxicity of Abeta1-42 and retard the
      deposition of amyloid plaques in adults with DS. However, there are conflicting
      data supporting an antagonist strategy to improve cognition in the presence of
      elevated levels of Abeta amyloidogenic peptides, as well as to prevent emergence
      of pyramidal neuron hyperexcitability. A major challenge to the implementation of
      clinical trials of targeted alpha7nAChR interventions in adults with DS will be
      the ability to detect medication-induced changes in cognition in the context of
      intellectual disability. The Review will consider some of the current evidence
      supporting both the role of the Abeta1-42-alpha7nAChR complex in the pathogenesis
      of the AD-like histopathology in adult persons with DS, and pharmacotherapeutic
      interventions with alpha7nAChR agonists. 

PMID- 24865151
TI  - Clinical implications of loudness dependence of auditory evoked potentials in
      patients with atypical depression.
AB  - OBJECTIVES: The loudness dependence of auditory evoked potentials (LDAEP) has
      been proposed as a useful biomarker of serotonin activity, and the LDAEP value is
      low in patients with melancholic depression. In this study, we evaluated LDAEP
      levels in patients with atypical depression. METHODS: We recruited 53 patients
      with atypical depression and 68 patients with non-atypical depression. Subjects
      were evaluated by the Atypical Depression Diagnostic Scale (ADDS), Hamilton
      Rating Scale for Depression (HAMD), Hamilton Rating Scale for Anxiety (HAMA),
      Beck Scale for Suicidal Ideation (BSI), Behavioral Inhibition System and
      Behavioral Activation System (BIS/BAS) scales, and Hypomanic Personality Scale
      (HPS). To determine LDAEP, the peak-to-peak N1/P2 was measured at five stimulus
      intensities and the LDAEP was calculated as the linear-regression slope. RESULTS:
      Patients with atypical depression had stronger LDAEP values and higher BAS and
      HPS scores than those with non-atypical depression. LDAEP showed a pattern of
      gradual decrease according to ADDS score hierarchy in patients with major
      depressive disorder. In the atypical depression group, LDAEP showed significant
      negative correlation with the BSI score and significant positive correlation with
      BAS score. In the non-atypical depression group, LDAEP did not show any
      significant correlations with the scores of psychological scales. CONCLUSIONS:
      Our results suggest that there is a relatively deficient serotonergic activity in
      patients with atypical depression and that LDAEP reflects mood reactivity. The
      transient drop of serotonergic activity induced by mood vulnerability might
      contribute to suicidal tendencies in patients with atypical depression.

PMID- 24865152
TI  - Estrogenic mediation of serotonergic and neurotrophic systems: implications for
      female mood disorders.
AB  - Clinical research has demonstrated a significant sex difference in the occurrence
      of depressive disorders. Beginning at pubertal onset, women report a higher
      incidence of depression than men. Women are also vulnerable to the development of
      depressive disorders such as premenstrual dysphoric disorder, postpartum
      depression, and perimenopausal depression. These disorders are associated with
      reproductive stages involving changes in gonadal hormone levels. Specifically,
      female depression and female affective behaviors are influenced by estradiol
      levels. This review argues two major mechanisms by which estrogens influence
      depression and depressive-like behavior: through interactions with neurotrophic
      factors and through an influence on the serotonergic system. In particular,
      estradiol increases brain derived neurotrophic factor (BDNF) levels within the
      brain, and alters serotonergic expression in a receptor subtype-specific manner.
      We will take a regional approach, examining these effects of estrogens in the
      major brain areas implicated in depression. Finally, we will discuss the gaps in
      our current knowledge of the effects of estrogens on female depression, and the
      potential utility for estrogen receptor modulators in treatment for this
      disorder. 

PMID- 24865146
TI  - Distribution of protein poly(ADP-ribosyl)ation systems across all domains of
      life.
AB  - Poly(ADP-ribosyl)ation is a post-translational modification of proteins involved
      in regulation of many cellular pathways. Poly(ADP-ribose) (PAR) consists of
      chains of repeating ADP-ribose nucleotide units and is synthesized by the family
      of enzymes called poly(ADP-ribose) polymerases (PARPs). This modification can be
      removed by the hydrolytic action of poly(ADP-ribose) glycohydrolase (PARG) and
      ADP-ribosylhydrolase 3 (ARH3). Hydrolytic activity of macrodomain proteins
      (MacroD1, MacroD2 and TARG1) is responsible for the removal of terminal ADP
      ribose unit and for complete reversion of protein ADP-ribosylation. Poly(ADP
      ribosyl)ation is widely utilized in eukaryotes and PARPs are present in
      representatives from all six major eukaryotic supergroups, with only a small
      number of eukaryotic species that do not possess PARP genes. The last common
      ancestor of all eukaryotes possessed at least five types of PARP proteins that
      include both mono and poly(ADP-ribosyl) transferases. Distribution of PARGs
      strictly follows the distribution of PARP proteins in eukaryotic species. At
      least one of the macrodomain proteins that hydrolyse terminal ADP-ribose is also
      always present. Therefore, we can presume that the last common ancestor of all
      eukaryotes possessed a fully functional and reversible PAR metabolism and that
      PAR signalling provided the conditions essential for survival of the ancestral
      eukaryote in its ancient environment. PARP proteins are far less prevalent in
      bacteria and were probably gained through horizontal gene transfer. Only eleven
      bacterial species possess all proteins essential for a functional PAR metabolism,
      although it is not known whether PAR metabolism is truly functional in bacteria.
      Several dsDNA viruses also possess PARP homologues, while no PARP proteins have
      been identified in any archaeal genome. Our analysis of the distribution of
      enzymes involved in PAR metabolism provides insight into the evolution of these
      important signalling systems, as well as providing the basis for selection of the
      appropriate genetic model organisms to study the physiology of the specific human
      PARP proteins. 

PMID- 24865153
TI  - The roles and mechanism of ultradian oscillatory expression of the mouse Hes
      genes.
AB  - Somites, metameric structures, give rise to the vertebral column, ribs, skeletal
      muscles and subcutaneous tissues. In mouse embryos, a pair of somites is formed
      every 2h by segmentation of the anterior parts of the presomitic mesoderm. This
      periodic event is regulated by a biological clock called the segmentation clock,
      which involves cyclic expression of the basic helix-loop-helix gene Hes7. Hes7
      oscillation is regulated by negative feedback with a delayed timing. This process
      has been mathematically simulated by differential-delay equations, which predict
      that negative feedback with shorter delays would abolish oscillations or produce
      dampened but more rapid oscillations. We found that reducing the number of
      introns within the Hes7 gene shortens the delay and abolishes Hes7 oscillation or
      results in a more rapid tempo of Hes7 oscillation, increasing the number of
      somites and vertebrae in the cervical and upper thoracic region. We also found
      that Hes1, a Hes7-related gene, is expressed in an oscillatory manner by many
      cell types, including fibroblasts and neural stem cells. In these cells, Hes1
      expression oscillates with a period of about 2-3h, and this oscillation is
      important for cell cycle progression. Furthermore, in neural stem cells, Hes1
      oscillation drives cyclic expression of the proneural genes Ascl1 and Neurogenin2
      and regulates multipotency. Hes1 expression oscillates more slowly in embryonic
      stem cells, and Hes1 oscillation regulates their fate preferences. Taken
      together, these results suggest that oscillatory expression with short periods
      (ultradian oscillation) is important for many biological events. 

PMID- 24865155
TI  - Characterization of membrane protein function by solid-state NMR spectroscopy.
AB  - Membrane proteins are an important class of biological molecules whose
      association with lipid bilayers and intrinsic molecular mobility can complicate
      their structural study by high-resolution methods. As different experimental
      techniques require different membrane mimetics, it can be challenging to relate
      membrane protein structure to function. This review presents examples of the use
      of solid-state nuclear magnetic resonance spectroscopy (ssNMR) to correlate
      structure and function in membrane proteins with diverse biological roles,
      including signaling, transport, and enzymatic reactions. The types of ssNMR
      experiments, as well as sources of complementary information and implications for
      biology, will be discussed. An outlook towards extending ssNMR studies to
      cellular preparations will be given.

PMID- 24865156
TI  - Design of proteins from smaller fragments-learning from evolution.
AB  - Nature has generated an impressive set of proteins with diverse folds and
      functions. It has been able to do so using mechanisms such as duplication and
      fusion as well as recombination of smaller protein fragments that serve as
      building blocks. These evolutionary mechanisms provide a template for the
      rational design of new proteins from fragments of existing proteins. Design by
      duplication and fusion has been explored for a number of symmetric protein folds,
      while design by rational recombination has just emerged. First experiments in
      recombining fragments from the same and different folds are proving successful in
      building new proteins that harbor easily evolvable properties originating from
      the parents. Overall, duplication and recombination of smaller fragments shows
      much potential for future applications in the design of proteins. 

PMID- 24865157
TI  - A geometric and dynamic affordance model of reaches-to-grasp: Men take greater
      risks than women.
AB  - Mon-Williams and Bingham (2011) developed an affordance model of the spatial
      structure of reaches-to-grasp. With a single free parameter (P), the model
      predicted the safety margins (SMs) exhibited in maximum grasp apertures (MGAs),
      during the approach of a hand to a target object, as a function of an affordance
      measure of object size and a functional measure of hand size. An affordance
      analysis revealed that object size is determined by a diagonal through the
      object, called the maximum object extent. Mon-Williams and Bingham provided no
      theoretical account for the empirically determined values of P. We now address
      this question. Snapp-Childs and Bingham (2009) augmented Warren's (1984)
      geometric affordance scaling model with a dynamical component determined by the
      stability of the motor performance. Because P was found to vary with the speeds
      of reaches, we incorporated a measure of the variability of performance into the
      model to yield predictions of P. We also found that P varied with gender. In
      respect to the size of safety margins, women were more conservative in taking
      risks then men. Finally, following Warren (1984), the classic paradigm for
      testing affordance models is to test the scaling relations with both small and
      large participants. We tested small- and large-handed men and small- and large
      handed women and found that the new parameter free model successfully accounted
      for the spatial structure of reaches-to-grasp.

PMID- 24865158
TI  - Unconscious processing of body actions primes subsequent action perception but
      not motor execution.
AB  - Previous studies have shown that viewing body actions primes not only the visual
      perception of congruent versus incongruent actions, but also their motor
      execution. Here, we used a masked-priming paradigm to explore whether
      visuoperceptual and visuomotor action priming may also occur when the prime is
      not consciously perceived. In 5 experiments, healthy individuals were presented
      with masked implied-action primes and were then prompted to perceive congruent or
      incongruent implied-action stimuli or to execute congruent or incongruent finger
      movements. Results showed that implied-action primes affected subsequent action
      perception also when they were not consciously perceived. Unconscious
      visuoperceptual action priming effects were independent from spatial
      compatibility and reflected genuine action representation. Conversely, masked
      implied-action primes affected motor preparation and execution processes only
      when they were consciously perceived. The results provide evidence of unconscious
      visuoperceptual but not visuomotor action priming effects, suggesting that
      unconscious processing of actions affects perceptual, but not motor
      representations.

PMID- 24865164
TI  - Three of 7 hemoglobin A1c point-of-care instruments do not meet generally
      accepted analytical performance criteria.
AB  - BACKGROUND: In 2009, we investigated the conformance of 8 hemoglobin A(1c) (Hb
      A(1c)) point-of-care (POC) instruments. Since then, instruments have improved and
      new devices are available on the market. In this second study, we evaluated the
      performance of DCA Vantage, Afinion, InnovaStar, Quo-Lab, Quo-Test, Cobas B101,
      and B-analyst Hb A(1c) POC instruments. METHODS: Clinical and Laboratory
      Standards Institute protocols EP-5 and EP-9 were applied to investigate
      imprecision, accuracy, and bias. We assessed bias using the mean of 3 certified
      secondary reference measurement procedures (SRMPs). Assay conformance with the
      National Glycohemoglobin Standardization Program (NGSP) certification criteria
      was also evaluated. Interference of common Hb variants was investigated for
      methods that could work with hemolysed material. RESULTS: The total CVs for all
      instruments, except for the DCA Vantage at a high Hb A(1c) value, were <=3.1% in
      SI units and <=2.1% in Diabetes Control and Complications Trial (DCCT) units.
      Afinion, DCA Vantage, B-analyst, and Cobas B101 instruments passed the NGSP
      criteria with 2 different reagent lot numbers. Quo-Test, Quo-Lab, and InnovaStar
      instruments had a negative bias compared to the mean of the 3 SRMPs and failed
      NGSP criteria. Most of the common Hb variants did not interfere with the
      investigated instruments, except Hb AE for the Cobas B101. CONCLUSIONS: Afinion,
      DCA Vantage, Cobas B101, and B-analyst instruments met the generally accepted
      performance criteria for Hb A(1c). Quo-Test, Quo-Lab, and InnovaStar met the
      criteria for precision but not for bias. Proficiency testing should be mandated
      for users of Hb A1c POC assays to ensure quality.

PMID- 24865165
TI  - Rapid increase in fall-induced cervical spine injuries among older Finnish adults
      between 1970 and 2011.
AB  - BACKGROUND: fall-related injuries in older adults are a major public heath
      challenge. METHODS: we determined the current trends in the number and age
      adjusted incidence of fall-induced severe cervical spine injuries among older
      adults in Finland by taking into account all persons in 50 years of age or older
      who were admitted to Finnish hospitals for primary treatment of these injuries
      between 1970 and 2011. Similar patients aged 20-49 years served as a reference
      group. RESULTS: the number of fall-induced cervical spine injuries among older
      Finns rose six-fold from 59 in 1970 to 372 in 2011. The age-adjusted incidence of
      injury (per 100 000 persons) was higher in men than in women throughout this
      period and showed a clear increase from 1970 to 2011: from 8.5 to 20.3 in men,
      and from 2.8 to 11.7 in women. In both sexes, the increase was most prominent in
      the oldest age group, persons aged 70 years or older. In the reference group, the
      injury incidence did not rise by time. CONCLUSIONS: the number and incidence of
      fall-induced severe cervical spine injuries among older Finns increased
      considerably between 1970 and 2011. An increase in the average risk of serious
      falls may partly explain the phenomenon. Wide-scale fall and injury prevention
      measures are urgently needed, because further ageing of the population is likely
      to worsen the problem in the near future.

PMID- 24865167
TI  - Genetic analysis of GABRB3 at 15q12 as a candidate gene of schizophrenia.
AB  - OBJECTIVE: Copy number variations encompassing the chromosome 15q11-q13 region
      have been implicated in the pathogenesis of several neurodevelopmental disorders
      including schizophrenia. The study aimed to investigate whether the GABRB3 gene
      mapped to 15q12 was associated with schizophrenia. MATERIALS AND METHODS: We
      resequenced the promoter and all the exonic regions of the GABRB3 gene in 349
      patients with schizophrenia and 386 control participants from Taiwan using the
      Sanger sequencing method. We also used a reporter gene assay to assess the
      functional impact of variants identified from the promoter region. RESULTS: We
      identified a total of six common single nucleotide polymorphisms and eight rare
      variants in this sample. No genetic association of these common single nucleotide
      polymorphisms with schizophrenia was detected. A missense mutation Y402H at exon
      9 was detected in two patients and two controls. Polyphen-2 predicted that the
      impact of this variant was benign. In addition, we identified two patient
      specific variants at the promoter of GABRB3 that showed significantly increased
      promoter activity in a reporter gene assay. CONCLUSION: The identification of two
      private patient-only variants at the promoter region with enhanced promoter
      activity supports the rare allele hypothesis of schizophrenia and suggests that
      increased GABRB3 expression may confer an increased risk of schizophrenia.

PMID- 24865169
TI  - Does thickness matter: ultrathin Descemet stripping automated endothelial
      keratoplasty.
AB  - PURPOSE OF REVIEW: Descemet stripping automated endothelial keratoplasty (DSAEK)
      has become worldwide the procedure of choice for the replacement of diseased
      corneal endothelium. More recently, ultrathin DSAEK (UT-DSAEK) has been
      introduced to guarantee better visual outcomes preserving good donor graft
      manipulation. RECENT FINDINGS: As DSAEK may still have major challenges such as
      suboptimal visual acuity and relatively slow visual rehabilitation, fairly new
      techniques such as UT-DSAEK and Descemet membrane endothelial keratoplasty (DMEK)
      have been introduced to allow much quicker and optimal visual rehabilitation.
      This article goes through the most recent findings and results of these
      techniques. SUMMARY: UT-DSAEK is a procedure that shares the improved visual
      outcome and lower immunologic rejection rate of DMEK over DSAEK, while minimizing
      all types of postoperative complications. In addition, similar to DSAEK and
      unlike DMEK, UT-DSAEK can be performed in all types of eyes, even in those with
      complicated anatomy or poor anterior chamber visualization.

PMID- 24865166
TI  - Effect of intervention aimed at increasing physical activity, reducing sedentary
      behaviour, and increasing fruit and vegetable consumption in children: active for
      Life Year 5 (AFLY5) school based cluster randomised controlled trial.
AB  - OBJECTIVE: To investigate the effectiveness of a school based intervention to
      increase physical activity, reduce sedentary behaviour, and increase fruit and
      vegetable consumption in children. DESIGN: Cluster randomised controlled trial.
      SETTING: 60 primary schools in the south west of England. PARTICIPANTS: Primary
      school children who were in school year 4 (age 8-9 years) at recruitment and
      baseline assessment, in year 5 during the intervention, and at the end of year 5
      (age 9-10) at follow-up assessment. INTERVENTION: The Active for Life Year 5
      (AFLY5) intervention consisted of teacher training, provision of lesson and child
      parent interactive homework plans, all materials required for lessons and
      homework, and written materials for school newsletters and parents. The
      intervention was delivered when children were in school year 5 (age 9-10 years).
      Schools allocated to control received standard teaching. MAIN OUTCOME MEASURES:
      The pre-specified primary outcomes were accelerometer assessed minutes of
      moderate to vigorous physical activity per day, accelerometer assessed minutes of
      sedentary behaviour per day, and reported daily consumption of servings of fruit
      and vegetables. RESULTS: 60 schools with more than 2221 children were recruited;
      valid data were available for fruit and vegetable consumption for 2121 children,
      for accelerometer assessed physical activity and sedentary behaviour for 1252
      children, and for secondary outcomes for between 1825 and 2212 children for the
      main analyses. None of the three primary outcomes differed between children in
      schools allocated to the AFLY5 intervention and those allocated to the control
      group. The difference in means comparing the intervention group with the control
      group was -1.35 (95% confidence interval -5.29 to 2.59) minutes per day for
      moderate to vigorous physical activity, -0.11 (-9.71 to 9.49) minutes per day for
      sedentary behaviour, and 0.08 (-0.12 to 0.28) servings per day for fruit and
      vegetable consumption. The intervention was effective for three out of nine of
      the secondary outcomes after multiple testing was taken into account: self
      reported time spent in screen viewing at the weekend (-21 (-37 to -4) minutes per
      day), self reported servings of snacks per day (-0.22 (-0.38 to -0.05)), and
      servings of high energy drinks per day (-0.26 (-0.43 to -0.10)) were all reduced.
      Results from a series of sensitivity analyses testing different assumptions about
      missing data and from per protocol analyses produced similar results. CONCLUSION:
      The findings suggest that the AFLY5 school based intervention is not effective at
      increasing levels of physical activity, decreasing sedentary behaviour, and
      increasing fruit and vegetable consumption in primary school children. Change in
      these activities may require more intensive behavioural interventions with
      children or upstream interventions at the family and societal level, as well as
      at the school environment level. These findings have relevance for researchers,
      policy makers, public health practitioners, and doctors who are involved in
      health promotion, policy making, and commissioning services. Trial registration
      Current Controlled Trials ISRCTN50133740.

PMID- 24865170
TI  - Trends in corneal transplantation: indications and techniques.
AB  - PURPOSE OF REVIEW: To describe trends in corneal transplantation surgery,
      including indications for surgery, evolution of lamellar keratoplasty, current
      surgical techniques, and future directions. RECENT FINDINGS: Over the past
      decade, anterior and posterior lamellar keratoplasty have begun to supplant
      penetrating keratoplasty. Surgical techniques continue to change and improve
      outcomes. In recent years, Descemet membrane endothelial keratoplasty (DMEK) has
      gained interest as it eliminates the corneal stromal interface, which may limit
      visual acuity after Descemet stripping automated endothelial keratoplasty.
      Despite the promising results with improved visual acuity and decreased
      rejection, the technical challenges associated with DMEK have limited widespread
      acceptance. With technical refinements and more eye banks providing precut tissue
      for both Descemet stripping automated endothelial keratoplasty and DMEK, it is
      likely both procedures will continue to increase over time. SUMMARY: Corneal
      transplantation has evolved rapidly over the past decade, from full-thickness
      penetrating keratoplasty towards lamellar keratoplasty to only remove and replace
      damaged layers of the cornea. Achieving minimal induced astigmatism with
      excellent visual acuity remains a challenge in corneal transplantation. Further
      refinements in surgical technique may help improve technical challenges and
      visual outcomes. In this article, we review changing trends in corneal
      transplantation and highlight developing medical treatments that may be available
      in the future.

PMID- 24865171
TI  - Management of residual refractive error after cataract surgery.
AB  - PURPOSE OF REVIEW: To provide a review of the recent literature on the management
      of residual refractive error after cataract surgery. RECENT FINDINGS: Laser in
      situ keratomileusis (LASIK) is the most accurate procedure to correct residual
      refractive error after cataract surgery. Lens-based procedures, such as
      intraocular lens (IOL) exchange or piggyback lens implantation, are also possible
      alternatives in cases with extreme ametropia, corneal abnormalities, or in
      situations where excimer laser is not available. In this review, we found that
      Piggyback IOL were safer and more accurate than IOL exchange. SUMMARY: Emmetropia
      is our main target today in modern cataract surgery. Accurate biometric analysis,
      selection and calculation of the adequate IOL, and modern techniques for cataract
      surgery all help surgeons to move toward the goal of cataract surgery as a
      refractive procedure free from refractive error. However, in spite of all these
      inputs, residual refractive error still occasionally occurs after cataract
      surgery and LASIK seems to be the most accurate method for its correction.

PMID- 24865172
TI  - Ocular surface diseases and corneal refractive surgery.
AB  - PURPOSE OF REVIEW: The purpose of this article is to provide an overview and
      update on recent literature regarding ocular surface disease and corneal
      refractive surgery. RECENT FINDINGS: Studies involving ocular surface disease
      and/or keratorefractive (corneal) surgery published found on the Medline database
      were included in the report. Studies focused on mechanisms of refractive surgery
      induced dry eye disease, surgical options, including modification of technique,
      to prevent dry eye, and postoperative dry eye prevention and management by way of
      both established and novel therapies. SUMMARY: By understanding the mechanisms of
      postoperative dry eye as well as patient risk factors for dry eye, patient
      satisfaction and surgical outcomes can be maximized. Patients identified as
      having an increased risk for postoperative dry eye may benefit from surgical
      techniques such as small-incision lenticule extraction (SMILE) and femtosecond
      laser-assisted in-situ keratomileusis (LASIK). Employing well known therapies
      such as preserved and nonpreserved artificial tears, nutritional supplements,
      topical cyclosporins, punctal plugs and autologus serum as well as novel
      therapies such as insulin-like growth factor 1, neuropeptides and acupuncture
      could provide improve outcomes and, if started early, could allow more patients
      to be candidates for corneal refractive surgery.

PMID- 24865173
TI  - 1D nanostructured Na7V4(P2O7)4(PO4) as high-potential and superior-performance
      cathode material for sodium-ion batteries.
AB  - Tailoring materials into nanostructure offers unprecedented opportunities in the
      utilization of their functional properties. High-purity Na7V4(P2O7)4(PO4) with 1D
      nanostructure is prepared as a cathode material for rechargeable Na-ion
      batteries. An efficient synthetic approach is developed by carefully controlling
      the crystal growth in the molten sodium phosphate. Based on the XRD, XPS, TG, and
      morphological characterization, a molten-salt assisted mechanism for
      nanoarchitecture formation is revealed. The prepared Na7V4(P2O7)4(PO4) nanorod
      has rectangle sides and preferential [001] growth orientation. GITT evaluation
      indicates that the sodium de/intercalation of Na7V4(P2O7)4(PO4) nanorod involves
      V(3+)/V(4+) redox reaction and Na5V(3.5+)4(P2O7)4(PO4) as intermediate phase,
      which results in two pairs of potential plateaus at the equilibrium potentials of
      3.8713 V (V(3+)/V(3.5+)) and 3.8879 V (V(3.5+)/V(4+)), respectively. The unique
      nanoarchitecture of the phase-pure Na7V4(P2O7)4(PO4) facilitates its reversible
      sodium de/intercalation, which is beneficial to the high-rate capability and the
      cycling stability. The Na7V4(P2O7)4(PO4) cathode delivers 80% of the capacity
      (obtained at C/20) at the 10 C rate and 95% of the initial capacity after 200
      cycles. Therefore, it is feasible to design and fabricate an advanced
      rechargeable sodium-ion battery by employment of 1D nanostructured
      Na7V4(P2O7)4(PO4) as the cathode material. 

PMID- 24865174
TI  - High-yield nontoxic gene transfer through conjugation of the CM18-Tat11 chimeric
      peptide with nanosecond electric pulses.
AB  - We report a novel nontoxic, high-yield, gene delivery system based on the
      synergistic use of nanosecond electric pulses (NPs) and nanomolar doses of the
      recently introduced CM18-Tat11 chimeric peptide (sequence of
      KWKLFKKIGAVLKVLTTGYGRKKRRQRRR, residues 1-7 of cecropin-A, 2-12 of melittin, and
      47-57 of HIV-1 Tat protein). This combined use makes it possible to drastically
      reduce the required CM18-Tat11 concentration and confines stable nanopore
      formation to vesicle membranes followed by DNA release, while no detectable
      perturbation of the plasma membrane is observed. Two different experimental
      assays are exploited to quantitatively evaluate the details of NPs and CM18-Tat11
      cooperation: (i) cytofluorimetric analysis of the integrity of synthetic 1,2
      dioleoyl-sn-glycero-3-phosphocholine giant unilamellar vesicles exposed to CM18
      Tat11 and NPs and (ii) the in vitro transfection efficiency of a green
      fluorescent protein-encoding plasmid conjugated to CM18-Tat11 in the presence of
      NPs. Data support a model in which NPs induce membrane perturbation in the form
      of transient pores on all cellular membranes, while the peptide stabilizes
      membrane defects selectively within endosomes. Interestingly, atomistic molecular
      dynamics simulations show that the latter activity can be specifically attributed
      to the CM18 module, while Tat11 remains essential for cargo binding and vector
      subcellular localization. We argue that this result represents a paradigmatic
      example that can open the way to other targeted delivery protocols. 

PMID- 24865175
TI  - Check-in and sorting of centrifuged serum and lithium-heparin tubes may be
      unsuitable using a bulk input module.
AB  - The aim of this study was to establish that laboratory testing may be impaired by
      pouring and sorting of centrifuged tubes into a bulk input module. The values of
      17 analytes, including albumin, aspartate aminotransferase (AST), bilirubin, urea
      nitrogen, C-reactive protein (CRP), calcium, chloride, cholesterol, creatine
      kinase (CK), creatinine, ferritin, glucose, lactate dehydrogenase (LDH),
      potassium, sodium, total protein, and thyroid-stimulating hormone (TSH), were
      measured in 29 centrifuged serum samples collected in tubes with gel separator
      and paired centrifuged lithium-heparin samples collected in tubes with gel
      separator, with (S-BIM) or without (S-NO-BIM) being poured and sorted by a bulk
      input module (Inpeco, Lugano, Switzerland). In serum tubes, significant
      differences were observed in S-BIM values of albumin, AST, cholesterol, ferritin,
      glucose, LDH, potassium, and sodium compared with S-NO-BIM, with bias of LDH
      exceeding the total allowable error. In lithium-heparin tubes, statistically
      significant differences were observed in S-BIM values of all parameters, except
      urea nitrogen, CRP, and sodium, compared with S-NO-BIM. The percentage bias of
      AST, LDH, glucose, and creatinine exceeded the total allowable error. These
      results demonstrate that check-in and sorting of centrifuged serum and lithium
      heparin tubes may be unsuitable using a bulk input module. 

PMID- 24865176
TI  - Large-area surface-enhanced Raman spectroscopy imaging of brain ischemia by gold
      nanoparticles grown on random nanoarrays of transparent boehmite.
AB  - Although SERS spectroscopy, which is sensitive to molecular vibration states,
      offers label-free visualization of molecules, identification of molecules and
      their reliable large-area imaging remains to be developed. Limitation comes from
      difficulties in fabricating a SERS-active substrate with homogeneity over a large
      area. Here, we overcome this hurdle by utilizing a self-assembled nanostructure
      of boehmite that is easily achieved by a hydrothermal preparation of aluminum as
      a template for subsequent gold (Au) deposition. This approach brought about
      random arrays of Au-nanostructures with a diameter of ~125 nm and a spacing of
      <10 nm, ideal for the hot-spots formation. The substrate, which we named "gold
      nanocoral" (GNC) after its coral reef-like shape, exhibited a small variability
      of signal intensities (coefficient value <11.2%) in detecting rhodamine 6G
      molecule when 121 spots were measured over an area of 10 * 10 mm(2), confirming
      high uniformity. The transparent nature of boehmite enabled us to conduct the
      measurement from the back-side of the substrate as efficiently as that from the
      front-side. We then conducted tissue imaging using the mouse ischemic brain
      adhered on the GNC substrate. Through nontargeted construction of two-dimensional
      Raman-intensity map using differential bands from two metabolically distinct
      regions, that is, ischemic core and contralateral-control areas, we found that
      mapping using the adenine ring vibration band at 736 cm(-1) clearly demarcated
      ischemic core where high-energy adenine phosphonucleotides were degraded as
      judged by imaging mass spectrometry. Such a detection capability makes the GNC
      based SERS technology especially promising for revealing acute energy derangement
      of tissues. 

PMID- 24865178
TI  - Boryl azides in 1,3-dipolar cycloadditions.
AB  - The 1,3-dipolar cycloaddition reaction of boron azides with alkynes has been
      investigated experimentally and computationally. At room temperature pinBN3 (pin
      = pinacolato) reacts with the strained triple bond of cyclooctyne with formation
      of an oligomeric boryl triazole. Alcoholysis of the oligomer yields the parent
      4,5,6,7,8,9-hexahydro-2H-cyclooctatriazole, which could be characterized as a
      hydrate by X-ray crystallography. A computational analysis of the reaction of tri
      and tetracoordinate boron azides R2BN3 (R = H, Me, pin, cat; cat = catecholato)
      and IMe.H2BN3 (IMe = 2,6-dimethylimidazole-2-ylidene) reveals significant
      differences in the reactivity depending on the coordination number: tricoordinate
      boron azides behave as type II 1,3-dipoles, while the tetracoordinate IMe.H2BN3
      is an electron-rich 1,3-dipole (type I) that strongly prefers reactions with
      electron-poor alkynes. 

PMID- 24865179
TI  - Comparative proteomics of short and tall glandular trichomes of Nicotiana tabacum
      reveals differential metabolic activities.
AB  - Leaf glandular trichomes (epidermal hairs) actively synthesize secondary
      metabolites, many of which are the frontline of plant defense. In Nicotiana
      tabacum, tall and short glandular trichomes have been identified. While the
      former have been extensively studied and match the classic picture of trichome
      function, the short trichomes have remained relatively uncharacterized. We have
      set up a procedure based on centrifugation on Percoll density gradients to obtain
      separate tall and short trichome fractions purified to >85%. We then investigated
      the proteome of both trichome types combining 2D-LC fractionation of tryptic
      peptides and quantification of a set of 461 protein groups using isobaric tags
      for relative and absolute quantitation. Almost the entire pathway leading to the
      synthesis of diterpenes was identified in the tall trichomes. Indications for
      their key roles in the synthesis of cuticular compounds were also found.
      Concerning the short glandular trichomes, ribosomal proteins and enzymes such
      phosphoenolpyruvate carboxykinase and polyphenol oxidase were more abundant than
      in the tall glandular trichomes. These results are discussed in the frame of
      several hypotheses regarding the respective roles of short and long glandular
      trichomes. 

PMID- 24865177
TI  - MitoNEET-mediated effects on browning of white adipose tissue.
AB  - MitoNEET is an outer mitochondrial membrane protein that, upon overexpression in
      white adipose tissue (WAT), exerts a positive impact on tissue expansion and
      whole-body lipid and carbohydrate homeostasis by altering mitochondrial matrix
      iron metabolism. Here we determine the key transcriptional events in subcutaneous
      WAT of mice in response to mitoNEET overexpression and a high-fat diet (HFD).
      Microarray analyses at key points during weight gain upon body weight divergence
      with wild-type mice demonstrate that mitoNEET-enriched sWAT early on, upregulates
      a browning signature programme that limits WAT expansion in transgenic mice for a
      period of up to 12 weeks of HFD. This compensatory browning phenotype is
      subsequently lost, resulting in rapid WAT expansion and body weight gain.
      Exposure to thermoneutral temperatures during HFD prompts weight gain
      significantly earlier. Similar WAT expansion is achieved upon infection with an
      adeno-associated virus expressing mitoNEET. Collectively, the mitoNEET-enriched
      fat pads feature a more vascularized, anti-inflammatory and less fibrotic
      environment. 

PMID- 24865181
TI  - Discovery of InsP6-kinases as InsP6-dephosphorylating enzymes provides a new
      mechanism of cytosolic InsP6 degradation driven by the cellular ATP/ADP ratio.
AB  - InsP6 (inositol hexakisphosphate), the most abundant inositol phosphate in
      metazoa, is pyrophosphorylated to InsP7 [5PP-InsP5 (diphosphoinositol
      pentakisphosphate)] by cytosolic and nuclear IP6Ks (InsP6 kinases) and to 1PP
      InsP5 by another InsP6/InsP7 kinase family. MINPP1 (multiple inositol
      polyphosphate phosphatase 1), the only known InsP6 phosphatase, is localized in
      the ER (endoplasmic reticulum) and lysosome lumina. A mechanism of cytosolic
      InsP6 dephosphorylation has remained enigmatic so far. In the present study, we
      demonstrated that IP6Ks change their kinase activity towards InsP6 at a
      decreasing ATP/ADP ratio to an ADP phosphotransferase activity and
      dephosphorylate InsP6. Enantio-selective analysis revealed that Ins(2,3,4,5,6)P5
      is the main InsP5 product of the IP6K reaction, whereas the exclusive product of
      MINPP1 activity is the enantiomer Ins(1,2,4,5,6)P5. Whereas lentiviral RNAi-based
      depletion of MINPP1 at falling cellular ATP/ADP ratios had no significant impact
      on Ins(2,3,4,5,6)P5 production, the use of the selective IP6K inhibitor TNP [N2
      (m-trifluorobenzyl),N6-(p-nitrobenzyl)purine] abolished the production of this
      enatiomer in different types of cells. Furthermore, by analysis of rat tissue and
      human blood samples all (main and minor) dephosphorylation products of InsP6 were
      detected in vivo. In summary, we identified IP6Ks as novel nuclear and cytosolic
      InsP6- (and InsP5-) dephosphorylating enzymes whose activity is sensitively
      driven by a decrease in the cellular ATP/ADP ratio, thus suggesting a role for
      IP6Ks as cellular adenylate energy 'sensors'. 

PMID- 24865180
TI  - Efficient synthesis of 3H-indoles enabled by the lead-mediated alpha-arylation of
      beta-ketoesters or gamma-lactams using aryl azides.
AB  - The development of a lead-mediated alpha-arylation reaction between aryl azides
      and beta-ketoesters or gamma-lactams that facilitates the formation of 3H-indoles
      is disclosed. Twenty-five examples are included which demonstrate the generality
      of this reaction to access aryl azides bearing tetrasubstituted o-alkyl
      substituents. When paired with a Staudinger reduction, this reaction streamlines
      the synthesis of functionalized 3H-indoles. 

PMID- 24865182
TI  - Interactions between doctors and pharmaceutical sales representatives in a former
      communist country. The ethical issues.
AB  - An anonymous survey distributed to doctors in Poland revealed the troublesome
      relationship between physicians and pharmaceutical sale representatives in terms
      of the frequency of visits, the trust of physicians in information supplied by
      sales reps, gifts accepted, and the general influence of marketing strategies on
      physician decisions. Challenges remain, despite laws enacted to address the
      problem.

PMID- 24865184
TI  - Role of the lymnaeid snail Pseudosuccinea columella in the transmission of the
      liver fluke Fasciola hepatica in Egypt.
AB  - Experimental infections of three Egyptian Pseudosuccinea columella populations
      with sympatric miracidia of Fasciola sp., coming from cattle- or sheep-collected
      eggs, were carried out to determine the capacity of this lymnaeid to support
      larval development of the parasite. Using microsatellite markers, the isolates of
      Egyptian miracidia were identified as Fasciola hepatica. Apart from being
      independent of snail origin, prevalences ranging from 60.4 to 75.5% in snails
      infected with five miracidia of F. hepatica were significantly higher than values
      of 30.4 to 42.2% in snails with bi-miracidial infections. The number of
      metacercariae ranged from 243 to 472 per cercarial-shedding snail and was
      independent of snail origin, parasite origin and miracidial dose used for
      infection. If P. columella was subjected to two successive bi-miracidial
      infections with F. hepatica, prevalence of infection was 63.3%, with a mean of
      311 metacercariae per snail. These values were clearly greater than those already
      reported for Radix natalensis infected with the same parasite and the same
      protocol. Successful experimental infection of P. columella with F. hepatica
      suggests that this lymnaeid snail is an important intermediate host for the
      transmission of fascioliasis in Egypt. 

PMID- 24865185
TI  - Packing for the journey: CHD5 remodels the genome.

PMID- 24865183
TI  - Surface chest motion decomposition for cardiovascular monitoring.
AB  - Surface chest motion can be easily monitored with a wide variety of sensors such
      as pressure belts, fiber Bragg gratings and inertial sensors, etc. The current
      applications of these sensors are mainly restricted to respiratory motion
      monitoring/analysis due to the technical challenges involved in separation of the
      cardiac motion from the dominant respiratory motion. The contribution of heart to
      the surface chest motion is relatively very small as compared to the respiratory
      motion. Further, the heart motion spectrally overlaps with the respiratory
      harmonics and their separation becomes even more challenging. In this paper, we
      approach this source separation problem with independent component analysis (ICA)
      framework. ICA with reference (ICA-R) yields only desired component with improved
      separation, but the method is highly sensitive to the reference generation.
      Several reference generation approaches are developed to solve the problem.
      Experimental validation of these proposed approaches is performed with chest
      displacement data and ECG obtained from healthy subjects under normal breathing
      and post-exercise conditions. The extracted component morphologically matches
      well with the collected ECG. Results show that the proposed methods perform
      better than conventional band pass filtering. 

PMID- 24865186
TI  - Prevalence of traumatic brain injury and access to services in an undergraduate
      population: a pilot study.
AB  - OBJECTIVES: The aim of this pilot study was to identify the prevalence of
      traumatic brain injury (TBI) among undergraduate college students, compare common
      TBI symptoms reported by students with and without a history of TBI and explore
      how often students with and without TBI access campus services. METHODS: A campus
      wide email recruited participants to an online survey containing questions about
      their history of TBI, experience of TBI symptoms and use of services. RESULTS: Of
      201 undergraduates, 55.7% reported no history of TBI or hospitalization, 27.9%
      reported a history of hospitalization but not TBI and 16.4% reported a history of
      TBI. Significant differences were seen among groups in their experience of some
      physical and psychosocial symptoms such as dizziness and difficulty with
      relationships. Healthy and TBI groups reported significantly more symptoms than
      the hospitalized group, but did not differ from each other. Most participants
      reported using no services and there were no significant differences in the
      average number of symptoms experienced by those seeking vs not seeking services.
      CONCLUSIONS: A substantial proportion of undergraduates reported a history of TBI
      and the experience of symptoms that could negatively impact academic performance.
      Further study is needed to examine factors influencing their use of available
      services.

PMID- 24865187
TI  - The antileukaemic cell cycle regulatory activities of swainsonine purified from
      Metarhizium anisopliae fermentation broth.
AB  - Swainsonine is a Metarhizium secondary metabolite known differentially for its
      specific mannosidase inhibitory, toxic and therapeutic activities. Here, the
      standard and purified swainsonine from Metarhizium anisopliae fermentation broth
      were comparatively evaluated for their in situ antileukaemic activities in human
      promyelocytic cell line, HL-60. Both the standard (IC50 = 6.96 MUM) and purified
      (IC50 = 9.50 MUM) compounds inhibited the leukaemic cell proliferation without
      inflicting cell membrane disruption at 48 h of post-treatment incubation. The DNA
      cell cycle analysis showed approximately 48.81% and 60.72% of the treated cells
      arrested in the synthetic phase (S-phase) at 36 and 48 h, respectively, upon
      treatment with IC50 concentration of the purified swainsonine. However, only
      29.62% of cells were arrested in S-phase with standard swainsonine at 48 h,
      suggesting the comprehensive action of certain other metabolites sharing the
      similar paradigm of antiproliferative properties in Metarhizium broth extract. 

PMID- 24865189
TI  - Subjective well-being of persons with type 2 diabetes mellitus.

PMID- 24865188
TI  - Association of microRNA-93, 190, 200b and receptor status in core biopsies from
      stage III breast cancer patients.
AB  - Oncologists now favor more personalized treatment strategies in breast cancer
      patients. Gene expression analysis has been widely used, but less is known about
      epigenetic factors, for example, microRNAs (miRNAs). The aim of this study was to
      determine the relationship between selected miRNAs and receptor status in core
      biopsies sampled before preoperative chemotherapy in stage III locally advanced
      breast cancer (LABC) patients. In 37 LABC core biopsies, three miRNAs per sample
      were analyzed: hsa-miR-93-5p, hsa-miR-190a, and hsa-miR-200b-3p, and hsa-miR-103a
      3p as an endogenous control (TaqMan((r)) RT-PCR; Applied Biosystems). Receptor
      status was determined by a dedicated pathologist. The Mann-Whitney U, Shapiro
      Wilk, and Levene's tests were used to compare related samples. Levels of miRNA-93
      differed significantly in core biopsies of LABC patients with different
      expressions of ER (estrogen receptor) and PR (progesterone receptor). Higher
      levels of miRNA-93 were found in ER-negative (p=0.0027) and PR-negative patients
      (p=0.0185). Levels of miRNA-190 and 200b did not differ significantly in core
      biopsies of LABC patients who expressed ER and PR differently (p=0.7727,
      p=0.9434, p=0.6213, and p=0.1717). Levels of miRNA-93, 190, and 200b were not
      significantly different in core biopsies of LABC patients with different HER2
      (human epidermal growth factor 2) expressions (p=0.8013, p=0.2609, and p=0.3222).
      The assessment of core biopsy miRNA profiles and receptor-based subtypes may
      identify new signaling pathways for improved breast cancer classification. 

PMID- 24865190
TI  - Association of specific genetic polymorphisms with age-related macular
      degeneration in a northern Chinese population.
AB  - PURPOSE: The associations between genetic variants located in CFH, CFB, ARMS2 and
      HTRA1 and the risk of age-related macular degeneration (AMD) in a northern
      Chinese population were investigated. METHODS: A case-control association study
      of 150 AMD patients and 145 ethnicity- and gender-matched controls were
      recruited. Genomic DNA was prepared from peripheral blood after the participants
      underwent comprehensive eye examinations. All individuals were genotyped for
      eight single nucleotide polymorphisms (SNPs) in four specific genes. Genotypic
      distribution was tested for Hardy-Weinberg equilibrium. Statistical analysis was
      performed for genotype, allele and haplotype frequencies along with their p
      values and corresponding odds ratios (OR), 95% confidence intervals (95% CI) and
      measures of linkage disequilibrium (LD). Bonferroni corrections for multiple
      comparisons were performed. RESULTS: Among the SNPs genotyped, p values of seven
      SNPs were less than 0.05 in the genotypic distributions and allele frequencies
      between AMD and control subjects. However, after Bonferroni correction, the
      genotype and allele distributions of two SNPs in CFH (rs10737680, rs1410996), one
      SNP (rs10490924) in ARMS2 and one SNP (rs11200638) in HTRA1 differed
      significantly between the controls and AMD patients. Two SNPs were significantly
      associated with AMD in the allele distributions. They were rs800292 (p(allele) =
      0.006, OR [CI] = 1.643[1.155-2.336]) in CFH and rs641153 (p(allele) = 0.002, OR
      [CI] = 0.273[0.120-0.620]) in CFB. Five haplotypes in CFH significantly
      predisposed patients to AMD after 50,000 permutations (p = 0.0099, p = 0.0099, p
      = 0.0013, p = 0.0414 and p = 0.0327). CONCLUSIONS: Gene variants in CFH, ARMS2
      and HTRA1 are related to an increased risk of AMD in a northern Chinese
      population.

PMID- 24865191
TI  - Genetic variants in the SKIV2L gene in exudative age-related macular degeneration
      in the Japanese population.
AB  - BACKGROUND: To investigate whether genetic variant in superkiller viralicidic
      activity 2-like (SKIV2L) gene is associated with exudative age-related macular
      degeneration (AMD) including neovascular AMD, polypoidal choroidal vasculopathy
      (PCV), and retinal angiomatous proliferation (RAP). MATERIALS AND METHODS: A
      total of 517 patients with exudative AMD comprised of 157patients with
      neovascular AMD, 333 patients with PCV, and 27patients with RAP, and 205 controls
      were enrolled in this study. Rs429608 inSKIV2L, rs800292 in complement factor H
      (CFH), rs10490924 in age-related maculopathy susceptibility2 (ARMS2) gene was
      genotyped using TaqMan technology. Logistic regression analysis was performed to
      correlate the risk for exudative AMD with demographic and genetic factors.
      RESULTS: The A allele frequency of rs429608 in the SKIV2L gene was significantly
      higher in controls (13.9%) than in those with neovascular AMD (5.7%, p = 0.002),
      PCV (7.2%, p = 0.003) and RAP (3.7%, p = 0.0345). After adjusting for age,
      gender, ARMS2 A69S, and CFHI62V, the A allele of rs429608 was significantly
      protective against neovascular AMD (odds ratio [OR] 0.24, 95% confidence interval
      [CI] 0.122-0.484, p < 0.001), PCV (OR 0.43, 95% CI 0.262-0.704, p = 0.001), RAP
      (OR 0.09, 95% CI 0.014-0.581, p = 0.011). CONCLUSIONS: A SKIV2L variant was
      associated with protection against exudative AMD regardless of subtypes in the
      Japanese population.

PMID- 24865192
TI  - Microdeletions involving chromosomes 12 and 22 associated with syndromic Duane
      retraction syndrome.
AB  - BACKGROUND: Duane retraction syndrome (DRS) is the most common of the congenital
      cranial dysinnervation disorders (CCDDs). CCDDs can be monogenic or chromosomal
      in origin. Identification of the genetic cause(s) in patients and families with
      DRS facilitates definitive diagnosis and provides insights into these
      developmental errors. MATERIALS AND METHODS: This study described a young girl
      with DRS on the left and several additional developmental abnormalities. Clinical
      examination including neuroimaging, sequencing of candidate genes associated with
      DRS, and array comparative genomic hybridization (array CGH) were performed.
      RESULTS: The proband had unilateral DRS type 3 on the left with somewhat low-set
      ears, mild motor delay with normal intelligence, and an asymmetric neck without a
      palpable right sternocleidomastoid muscle. Spine X-rays revealed a Klippel-Feil
      syndrome (KFS) and an MRI showed a webbed neck. She also had spina bifida at C8
      T1 and a submucosal cleft palate. The parents of the proband were related with no
      other family member affected similarly. Sequencing of SALL4, CHN1, HOXA1, and
      TUBB3 did not show any mutation. Array CGH revealed de novo deletions of 21 Kb on
      chromosome 12q24.31 and 11 Kb on chromosome 22q13.31, each encompassing only one
      gene, ring finger protein 34, E3 ubiquitin protein ligase (RNF34) and peroxisome
      proliferator-activated receptor alpha (PPARA) respectively. CONCLUSIONS: This
      patient presents an unusual phenotype associated with a unique combination of two
      chromosomal microdeletions.

PMID- 24865196
TI  - Commentary on "The Army Study to Assess Risk and Resilience in Servicemembers
      (Army STARRS)": Army STARRS: a Framingham-like study of psychological health risk
      factors in soldiers.
AB  - Although historically the Army suicide rate has been significantly lower than the
      civilian rate, in 2004, the suicide and accidental death rates began trending
      upward. By 2008, the Army suicide rate had risen above the national average (20.2
      per 100,000). In 2009, 160 active duty Soldiers took their lives, making suicide
      the third leading cause of death among the Army population. If accidental death,
      frequently the result of high-risk behavior, is included, then more Soldiers died
      by their own actions than in combat in 2009. The Army Study to Assess Risk and
      Resilience in Servicemembers (Army STARRS) was thus created in 2009 to begin to
      address these problems. The Army STARRS project is a large consortium of seven
      different studies to develop data-driven methods for mitigating or preventing
      suicide behaviors and improving the overall mental health and behavioral
      functioning of Army Soldiers during and after their Army service. The first
      research articles from the Army STARRS project were published in late 2013 and
      early 2014. This work has already begun to outline important facets of risk in
      the military, and it is helping to drive an empirically derived approach to
      improvements in understanding mental disorders and risk behavior and to improve
      prevention and support of mental health and resilience. The Framingham Heart
      Study, started in the 1940s, marked a watershed event in utilizing large cross
      sectional and prospective longitudinal collaborative research to identify and
      understand risk factors for cardiovascular disease. The Army STARRS project,
      through its collaborative, prospective, and robust innovative design and
      implementation, may provide the beginning of a similar scientific cohort in
      mental disorders. The work of this project will help understand biological and
      psychological aspects of military service, including those leading to suicide.
      When coupled with timely feedback to Army leadership, it permits near real-time
      steps to diagnose, mitigate, and manage emerging mental health issues and the
      root causes of risk and resilience in Army Soldiers, with potential impact
      extending across many traumatized populations-not unlike a parallel process that
      has markedly improved survival and recovery from physical combat wounds. 

PMID- 24865195
TI  - The Army study to assess risk and resilience in servicemembers (Army STARRS).
AB  - IMPORTANCE/OBJECTIVE: Although the suicide rate in the U.S. Army has
      traditionally been below age-gender matched civilian rates, it has climbed
      steadily since the beginning of the Iraq and Afghanistan conflicts and since 2008
      has exceeded the demographically matched civilian rate. The Army Study to Assess
      Risk and Resilience in Servicemembers (Army STARRS) is a multicomponent
      epidemiological and neurobiological study designed to generate actionable
      evidence-based recommendations to reduce Army suicides and increase knowledge
      about risk and resilience factors for suicidality and its psychopathological
      correlates. This paper presents an overview of the Army STARRS component study
      designs and of recent findings. DESIGN/SETTING/PARTICIPANTS/INTERVENTION: Army
      STARRS includes six main component studies: (1) the Historical Administrative
      Data Study (HADS) of Army and Department of Defense (DoD) administrative data
      systems (including records of suicidal behaviors) for all soldiers on active duty
      2004-2009 aimed at finding administrative record predictors of suicides; (2)
      retrospective case-control studies of fatal and nonfatal suicidal behaviors (each
      planned to have n = 150 cases and n = 300 controls); (3) a study of new soldiers
      (n = 50,765 completed surveys) assessed just before beginning basic combat
      training (BCT) with self-administered questionnaires (SAQ), neurocognitive tests,
      and blood samples; (4) a cross-sectional study of approximately 35,000 (completed
      SAQs) soldiers representative of all other (i.e., exclusive of BCT) active duty
      soldiers; (5) a pre-post deployment study (with blood samples) of soldiers in
      brigade combat teams about to deploy to Afghanistan (n = 9,421 completed baseline
      surveys), with sub-samples assessed again one, three, and nine months after
      returning from deployment; and (6) a pilot study to follow-up SAQ respondents
      transitioning to civilian life. Army/DoD administrative data are being linked
      prospectively to the large-scale survey samples to examine predictors of
      subsequent suicidality and related mental health outcomes. MAIN OUTCOME MEASURES:
      Measures (self-report and administratively recorded) of suicidal behaviors and
      their psychopathological correlates. RESULTS: Component study cooperation rates
      are comparatively high. Sample biases are relatively small. Inefficiencies
      introduced into parameter estimates by using nonresponse adjustment weights and
      time-space clustering are small. Initial findings show that the suicide death
      rate, which rose over 2004-2009, increased for those deployed, those never
      deployed, and those previously deployed. Analyses of administrative records show
      that those deployed or previously deployed were at greater suicide risk.
      Receiving a waiver to enter the Army was not associated with increased risk.
      However, being demoted in the past two years was associated with increased risk.
      Time in current deployment, length of time since return from most recent
      deployment, total number of deployments, and time interval between most recent
      deployments (known as dwell time) were not associated with suicide risk. Initial
      analyses of survey data show that 13.9% of currently active non-deployed regular
      Army soldiers considered suicide at some point in their lifetime, while 5.3% had
      made a suicide plan, and 2.4% had attempted suicide. Importantly, 47-60% of these
      outcomes first occurred prior to enlistment. Prior mental disorders, in
      particular major depression and intermittent explosive disorder, were the
      strongest predictors of these self-reported suicidal behaviors. Most onsets of
      plans-attempts among ideators (58.3-63.3%) occurred within the year of onset of
      ideation. About 25.1% of non-deployed U.S. Army personnel met 30-day criteria for
      a DSM-IV anxiety, mood, disruptive behavior, or substance disorder (15.0% an
      internalizing disorder; 18.4% an externalizing disorder) and 11.1% for multiple
      disorders. Importantly, three-fourths of these disorders had pre-enlistment
      onsets. CONCLUSIONS: Integration across component studies creates strengths going
      well beyond those in conventional applications of the same individual study
      designs. These design features create a strong methodological foundation from
      which Army STARRS can pursue its substantive research goals. The early findings
      reported here illustrate the importance of the study and its approach as a model
      of studying rare events particularly of national security concern. Continuing
      analyses of the data will inform suicide prevention for the U.S. Army.

PMID- 24865198
TI  - Five-year follow-up of supportive psychodynamic psychotherapy in first-episode
      psychosis: long-term outcome in social functioning.
AB  - OBJECTIVES: The long-term outcomes of several approaches to intervention
      targeting social functioning in schizophrenia are not well documented.
      Contemporary supportive psychodynamic psychotherapy (SPP) aims to improve social
      functioning. The aim of the present study was to investigate the long-term
      outcome of SPP in a prospective, longitudinal, comparative, multicenter
      investigation of successively referred patients diagnosed with first-episode
      schizophrenia spectrum disorder. METHOD: Manualized SPP for up to 3 years as a
      supplement to standard treatment (ST) were compared to ST alone and followed up
      for 5 years (N = 269). The SPP targeted interpersonal relationships, emotion
      regulation, social cognition, and self-coherence. RESULTS: Significant between
      group effects in favor of SPP+ST on social functioning, overall symptoms, and
      positive psychotic symptoms were found during the period of active SPP
      intervention. These differential effects, however, were not sustained after end
      of additional SPP at 5-year follow-up. CONCLUSION: The findings are in line with
      results from other approaches targeting social functioning in schizophrenia and
      support SPP as a valuable treatment. Further research into the curative elements
      of SPP is needed.

PMID- 24865199
TI  - Dispelling myths about dissociative identity disorder treatment: an empirically
      based approach.
AB  - OBJECTIVE: Some claim that treatment for dissociative identity disorder (DID) is
      harmful. Others maintain that the available data support the view that
      psychotherapy is helpful. METHOD: We review the empirical support for both
      arguments. RESULTS: Current evidence supports the conclusion that phasic
      treatment consistent with expert consensus guidelines is associated with
      improvements in a wide range of DID patients' symptoms and functioning, decreased
      rates of hospitalization, and reduced costs of treatment. Research indicates that
      poor outcome is associated with treatment that does not specifically involve
      direct engagement with DID self-states to repair identity fragmentation and to
      decrease dissociative amnesia. CONCLUSIONS: The evidence demonstrates that
      carefully staged trauma-focused psychotherapy for DID results in improvement,
      whereas dissociative symptoms persist when not specifically targeted in
      treatment. The claims that DID treatment is harmful are based on anecdotal cases,
      opinion pieces, reports of damage that are not substantiated in the scientific
      literature, misrepresentations of the data, and misunderstandings about DID
      treatment and the phenomenology of DID. Given the severe symptomatology and
      disability associated with DID, iatrogenic harm is far more likely to come from
      depriving DID patients of treatment that is consistent with expert consensus,
      treatment guidelines, and current research.

PMID- 24865200
TI  - Psychological effects of disaster relief activities on Japan ground self-defense
      force personnel following the 2011 great east Japan earthquake.
AB  - OBJECTIVE: Disaster relief workers are potentially exposed to severe stressors on
      the job, resulting in a variety of psychological responses. This study aims to
      clarify the psychological effects of disaster relief activities on Japan Ground
      Self-Defense Force (JGSDF) personnel following the 2011 Great East Japan
      Earthquake. METHOD: A self-report questionnaire was administered to 606 JGSDF
      personnel one month after completing the disaster relief mission. Posttraumatic
      stress responses and general psychological distress were assessed using the
      Impact of Event Scale-Revised (IES-R) and the K10 scales. Associations between
      outcome variables and independent variables (age, gender, military rank, length
      of deployment, and exposure to dead bodies) were measured with univariate
      analyses and subsequent multiple logistic regression analyses. RESULTS: The mean
      (+/- SD) IES-R score was 6.2 (+/- 8.1), and the mean K10 score was 12.8 (+/-
      4.4). In the univariate analyses, exposure to dead bodies and age were identified
      as significant factors for IES-R and K10 scores, (p < 0.01). However, the
      multiple logistic regression analyses did not reveal any significant factors
      although body handlers' exposure approached significance for IES-R. CONCLUSIONS:
      The subjects reported very low psychological responses despite the severe nature
      of their disaster relief activities. Several factors may account for the low
      levels of psychological distress and posttraumatic symptoms observed in this
      study.

PMID- 24865197
TI  - Culture and psychiatric evaluation: operationalizing cultural formulation for DSM
      5.
AB  - The Outline for Cultural Formulation (OCF) introduced with DSM-IV provided a
      framework for clinicians to organize cultural information relevant to diagnostic
      assessment and treatment planning. However, use of the OCF has been inconsistent,
      raising questions about the need for guidance on implementation, training, and
      application in diverse settings. To address this need, DSM-5 introduced a
      cultural formulation interview (CFI) that operationalizes the process of data
      collection for the OCF. The CFI includes patient and informant versions and 12
      supplementary modules addressing specific domains of the OCF. This article
      summarizes the literature reviews and analyses of experience with the OCF
      conducted by the DSM-5 Cross-Cultural Issues Subgroup (DCCIS) that informed the
      development of the CFI. We review the history and contents of the DSM-IV OCF, its
      use in training programs, and previous attempts to render it operational through
      questionnaires, protocols, and semi-structured interview formats. Results of
      research based on the OCF are discussed. For each domain of the OCF, we summarize
      findings from the DCCIS that led to content revision and operationalization in
      the CFI. The conclusion discusses training and implementation issues essential to
      service delivery. 

PMID- 24865202
TI  - Could spice drugs induce psychosis with abnormal movements similar to catatonia?

PMID- 24865201
TI  - Examining disaster mental health workforce capacity.
AB  - OBJECTIVE: We examined the capacity of the disaster mental health workforce in
      Victoria, Australia, to provide the three evidence-supported intervention types
      of psychological first aid, skills for psychological recovery, and intensive
      mental health treatments. METHOD: Utilizing data from a cross-professional, state
      level disaster mental health workforce survey (n = 791), we developed composite
      capacity indicators (CCI) for each intervention and performed logistic regression
      analyses to examine key predictors of disaster mental health workforce capacity.
      RESULTS: CCI profiles highlighted significant gaps in the disaster mental health
      capacity of Victorian providers, with only 32-42% able to deliver current best
      practice interventions. Key predictors of workforce capacity common and unique to
      interventions were highlighted. CONCLUSIONS: Key strategies to raise Victoria's
      disaster mental health workforce capacity should focus on targeted multilevel
      training in best practice interventions, creation of practice opportunities, and
      structural provider support/engagement. CCIs focused on best practice
      interventions provide a methodology for rapid workforce capacity assessment that
      can facilitate disaster preparedness planning, capacity building, and delivery of
      quality disaster mental health services.

PMID- 24865204
TI  - What's missing in missing data? Omissions in survey responses among parents of
      children with advanced cancer.
AB  - BACKGROUND: Missing data is a common phenomenon with survey-based research;
      patterns of missing data may elucidate why participants decline to answer certain
      questions. OBJECTIVE: To describe patterns of missing data in the Pediatric
      Quality of Life and Evaluation of Symptoms Technology (PediQUEST) study, and
      highlight challenges in asking sensitive research questions. DESIGN: Cross
      sectional, survey-based study embedded within a randomized controlled trial.
      SETTING: Three large children's hospitals: Dana-Farber/Boston Children's Cancer
      and Blood Disorders Center (DF/BCCDC); Children's Hospital of Philadelphia
      (CHOP); and Seattle Children's Hospital (SCH). MEASUREMENTS: At the time of their
      child's enrollment, parents completed the Survey about Caring for Children with
      Cancer (SCCC), including demographics, perceptions of prognosis, treatment goals,
      quality of life, and psychological distress. RESULTS: Eighty-six of 104 parents
      completed surveys (83% response). The proportion of missing data varied by
      question type. While 14 parents (16%) left demographic fields blank, over half
      (n=48; 56%) declined to answer at least one question about their child's
      prognosis, especially life expectancy. The presence of missing data was unrelated
      to the child's diagnosis, time from progression, time to death, or parent
      distress (p>0.3 for each). Written explanations in survey margins suggested that
      addressing a child's life expectancy is particularly challenging for parents.
      CONCLUSIONS AND RELEVANCE: Parents of children with cancer commonly refrain from
      answering questions about their child's prognosis, however, they may be more
      likely to address general cure likelihood than explicit life expectancy.
      Understanding acceptability of sensitive questions in survey-based research will
      foster higher quality palliative care research.

PMID- 24865205
TI  - A method of extracting structural priors from images of micro-CT for fluorescence
      molecular tomography reconstruction.
AB  - The dual-modality systems combined fluorescence molecular tomography (FMT) and
      micro-computed tomography (micro-CT) can provide molecular and anatomical
      information of small animals simultaneously. Except for anatomic localization,
      micro-CT should also offer boundary of different organs as reconstruction priors
      for FMT, which is more challenging than acquisition of structural information. In
      this paper, we propose a framework to extract structural priors of a living mouse
      with micro-CT. The iodinated lipid emulsion contrast agent was adopted to enhance
      the contrast of the soft tissues of the mouse. Then organs in thorax and abdomen
      were segmented with different approaches depending on the characteristics of the
      organs. Bone, lung, heart, liver, spleen, and muscles were separately segmented.
      And the results were compared with that manually segmented. The Tanimoto
      coefficient and the relative volume difference of segmented slices were measured
      to be 91.28 +/- 5.78 and 0.27 +/- 3.15, respectively. In our simulation study of
      FMT reconstruction, the errors of measured position and concentration of the
      fluorophore with priors declined by 89.7% and 79.6% in thorax, as well as 80.8%
      and 78.3% in abdomen, respectively, compared with the results without priors. The
      proposed scheme will make FMT reconstruction much more reliable and practical in
      small animal study. 

PMID- 24865206
TI  - Study of solid-conversion gaseous detector based on GEM for high energy X-ray
      industrial CT.
AB  - The general gaseous ionization detectors are not suitable for high energy X-ray
      industrial computed tomography (HEICT) because of their inherent limitations,
      especially low detective efficiency and large volume. The goal of this study was
      to investigate a new type of gaseous detector to solve these problems. The novel
      detector was made by a metal foil as X-ray convertor to improve the conversion
      efficiency, and the Gas Electron Multiplier (hereinafter "GEM") was used as
      electron amplifier to lessen its volume. The detective mechanism and signal
      formation of the detector was discussed in detail. The conversion efficiency was
      calculated by using EGSnrc Monte Carlo code, and the transport course of photon
      and secondary electron avalanche in the detector was simulated with the Maxwell
      and Garfield codes. The result indicated that this detector has higher conversion
      efficiency as well as less volume. Theoretically this kind of detector could be a
      perfect candidate for replacing the conventional detector in HEICT. 

PMID- 24865207
TI  - Impact of physician practice on patient radiation dose during CT guided biopsy
      procedures.
AB  - PURPOSE: Patient radiation dose during Computed Tomography (CT) guided biopsy
      procedures is determined by both acquisition technical parameters and physician
      practice. The potential effect of the physician practice is of concern. This
      study is to investigate the effects of those intangibles on patient radiation
      dose. METHODS: Patient radiation dose from 252 patients who underwent CT guided
      biopsy from 2009 to 2010 were retrospectively studied. Ten physicians who used
      conventional intermittent shots, low mA dose saving feature, or both were
      included in the study. The patient dose reports were retrieved and the total dose
      length products (DLPs) were analyzed. Linear regression analysis performed
      between various variables and reported dose. Patient detriment index (PDI) was
      developed, which sets threshold (standard of practice) for comparing physician
      practice with their peers. Odds ratio was calculated to determine odds of a group
      of patients receiving dose above threshold when compared to another group.
      RESULTS: Median DLP among ten physicians was 1194 mGy-cm. There was a significant
      difference (p< 0.01) between reported DLPs doses when physicians used dose saving
      feature vs. when feature not used (539.8 +/- 169.4 mGy-cm vs. 1269.7 +/- 659.0
      mGy-cm). In general, physicians who used dose saving feature had lower relative
      PDIs (< 1) compared to the PDIs (> 1) without the dose feature. Odds ratio
      estimate of 7.7 at 95% confidence level indicates that the odds of a group
      receiving a high dose depends on practitioner. CONCLUSION: Adjustments of
      practice habits, use of dose saving features or both may be needed to improve
      patient care for CT biopsy.

PMID- 24865208
TI  - Image quality and dose efficiency of high energy phase sensitive x-ray imaging:
      phantom studies.
AB  - The goal of this preliminary study was to perform an image quality comparison of
      high energy phase sensitive imaging with low energy conventional imaging at
      similar radiation doses. The comparison was performed with the following
      phantoms: American College of Radiology (ACR), contrast-detail (CD), acrylic edge
      and tissue-equivalent. Visual comparison of the phantom images indicated
      comparable or improved image quality for all phantoms. Quantitative comparisons
      were performed through ACR and CD observer studies, both of which indicated
      higher image quality in the high energy phase sensitive images. The results of
      this study demonstrate the ability of high energy phase sensitive imaging to
      overcome existing challenges with the clinical implementation of phase contrast
      imaging and improve the image quality for a similar radiation dose as compared to
      conventional imaging near typical mammography energies. In addition, the results
      illustrate the capability of phase sensitive imaging to sustain the image quality
      improvement at high x-ray energies and for breast simulating phantoms, both of
      which indicate the potential to benefit fields such as mammography. Future
      studies will continue to investigate the potential for dose reduction and image
      quality improvement provided by high energy phase sensitive imaging. 

PMID- 24865209
TI  - Edge guided image reconstruction in linear scan CT by weighted alternating
      direction TV minimization.
AB  - Linear scan computed tomography (CT) is a promising imaging configuration with
      high scanning efficiency while the data set is under-sampled and angularly
      limited for which high quality image reconstruction is challenging. In this work,
      an edge guided total variation minimization reconstruction (EGTVM) algorithm is
      developed in dealing with this problem. The proposed method is modeled on the
      combination of total variation (TV) regularization and iterative edge detection
      strategy. In the proposed method, the edge weights of intermediate
      reconstructions are incorporated into the TV objective function. The optimization
      is efficiently solved by applying alternating direction method of multipliers. A
      prudential and conservative edge detection strategy proposed in this paper can
      obtain the true edges while restricting the errors within an acceptable degree.
      Based on the comparison on both simulation studies and real CT data set
      reconstructions, EGTVM provides comparable or even better quality compared to the
      non-edge guided reconstruction and adaptive steepest descent-projection onto
      convex sets method. With the utilization of weighted alternating direction TV
      minimization and edge detection, EGTVM achieves fast and robust convergence and
      reconstructs high quality image when applied in linear scan CT with under-sampled
      data set. 

PMID- 24865210
TI  - Theoretical modeling of mobile target broadening in helical and axial computed
      tomographic imaging.
AB  - PURPOSE: To investigate variations in mobile target length induced by sinusoidal
      motion in helical (HCT) and axial CT (ACT) imaging. A mathematical model was
      derived that predicts the measured broadening of the apparent lengths of mobile
      targets and its dependence on motion parameters, target size, and imaging couch
      speed in CT images. MATERIALS AND METHODS: Three mobile targets of differing
      lengths and sizes were constructed of tissue-equivalent gel material and embedded
      into artificial lung phantom. Respiratory motion was mimicked with a mobile
      phantom that moves in one-dimension along the superior-inferior direction with
      sinusoidal motion patterns. A mathematical model was derived to predict
      quantitatively the variations of apparent lengths for mobile targets and its
      dependence on phantom and imaging couch motion parameters in HCT and ACT. The
      model predictions were verified by length measurements of the mobile phantom
      targets that were imaged with the different motion patterns using CT imaging.
      RESULTS: The measured lengths of mobile targets enlarged or shrunk depending on
      the phantom motion parameters that include phantom speed, amplitude, frequency,
      phase and speed of the imaging couch. The target length variations were
      significant where some targets doubled lengths or shrunk to less than half of
      their actual length. The apparent lengths of mobile targets decreased if the
      target was moving in the same direction as the imaging couch motion and increased
      if the mobile target was moving opposed to imaging couch in both HCT and ACT. The
      model predicts well the variations in the mobile target apparent lengths and
      their dependence on the motion parameters. CONCLUSION: The measured and model
      variations of apparent lengths of mobile targets are considerable and may affect
      the accuracy of tumor volumes obtained from HCT and ACT. This mathematical model
      provides a method to quantitatively assess the length variations of mobile
      targets and their dependence on motion parameters of the phantom and imaging
      system which may have potential applications in the fields of diagnostic imaging
      and radiotherapy.

PMID- 24865212
TI  - Combined multi-kernel head computed tomography images optimized for depicting
      both brain parenchyma and bone.
AB  - BACKGROUND: The hybrid convolution kernel technique for computed tomography (CT)
      is known to enable the depiction of an image set using different window settings.
      OBJECTIVE: Our purpose was to decrease the number of artifacts in the hybrid
      convolution kernel technique for head CT and to determine whether our improved
      combined multi-kernel head CT images enabled diagnosis as a substitute for both
      brain (low-pass kernel-reconstructed) and bone (high-pass kernel-reconstructed)
      images. METHODS: Forty-four patients with nondisplaced skull fractures were
      included. Our improved multi-kernel images were generated so that pixels of >100
      Hounsfield unit in both brain and bone images were composed of CT values of bone
      images and other pixels were composed of CT values of brain images. Three
      radiologists compared the improved multi-kernel images with bone images. RESULTS:
      The improved multi-kernel images and brain images were identically displayed on
      the brain window settings. All three radiologists agreed that the improved multi
      kernel images on the bone window settings were sufficient for diagnosing skull
      fractures in all patients. CONCLUSIONS: This improved multi-kernel technique has
      a simple algorithm and is practical for clinical use. Thus, simplified head CT
      examinations and fewer images that need to be stored can be expected.

PMID- 24865211
TI  - Study on image processing of panoramic X-ray using deviation improvement
      software.
AB  - Utilization of panoramic X-ray device is getting wider. Panoramic X-ray has low
      resolution than general X-ray device and it occurs to distortion by deviation of
      image synthesis. Due to structural problems, it has been used restrictively to
      identify of tooth structure, not for whole head. Therefore, it designed and
      produced panoramic X-ray device which is possible to diagnostic coverage can be
      extended and had to be adjusted interval control between X-ray generator and
      image processing for whole of Maxillofacia's diagnosis. Produced panoramic X-ray
      device is composed basically of short image synthesis. In addition, it was
      confirmed the results by used the device which was applied deviation of the
      brightness of the image, filter to improve the location of the deviation and
      interpolation method. In this study, it was used 13 images including the front.
      It occurs to brightness deviation, position deviation, and geometric correction
      when synthesis of image, but it had been solved by deviation improvement software
      and a change of CCD camera's scan line which is used for image acquisition.
      Therefore, it confirmed expansion possibility of utilization range to commonly
      used panoramic X-ray device. 

PMID- 24865213
TI  - Evaluation of automatic exposure control options in digital mammography.
AB  - To quantify the trade-offs of dose and image quality among pre-loaded automatic
      exposure control (AEC) options in digital mammography, two AEC tables from the
      Hologic Selenia digital mammography system were compared: the default AEC "table
      0" and AEC "table 1". Realistically-shaped phantoms consisting of tissue
      equivalent material of various thicknesses (4.5 cm-7 cm) were imaged to obtain a
      figure of merit (FOM), the squared contrast-to-noise ratio per mean glandular
      dose. To relate the results to pathological findings and to evaluate the overall
      performance, the measured contrast-to-noise ratios were applied to simulated
      lesions on the anthropomorphic breast phantom images, producing various lesion
      configurations which were blindly scored. It was found that the AEC table 1
      improves the low contrast FOM by 11% to 20% for the breast thicknesses of 4.5-6
      cm. However, for the 7 cm thick breast, the AEC table 1 decreases the low
      contrast FOM by 17%. For microcalcifications, the AEC table 1 improves the FOM
      slightly for the breast thicknesses of 4.5--6 cm and decreases it by 18% at a
      thickness of 7 cm. The lesion simulation showed enhanced contrast due to the AEC
      table 1 for the breast thicknesses of 5 cm, 6 cm, and 7 cm, but the enhancement
      gradually reduces as the thickness increases. The lesion reading showed that the
      microcalcification detection was scored significantly higher from the AEC table 1
      for the thicknesses 5 cm, 6 cm, and 7 cm. The corresponding improvement of mass
      detection scores was also observed but not consistently significant over the
      thickness range. 

PMID- 24865214
TI  - Optimization of X-ray microplanar beam radiation therapy for deep-seated tumors
      by a simulation study.
AB  - A Monte Carlo simulation was applied to study the energy dependence on the
      transverse dose distribution of microplanar beam radiation therapy (MRT) for deep
      seated tumors. The distribution was found to be the peak (in-beam) dose and the
      decay from the edge of the beam down to the valley. The area below the same
      valley dose level (valley region) was decreased with the increase in the energy
      of X-rays at the same beam separation. To optimize the MRT, we made the following
      two assumptions: the therapeutic gain may be attributed to the efficient recovery
      of normal tissue caused by the beam separation; and a key factor for the
      efficient recovery of normal tissue depends on the area size of the valley
      region. Based on these assumptions and the results of the simulated dose
      distribution, we concluded that the optimum X-ray energy was in the range of 100
      300 keV depending on the effective peak dose to the target tumors and/or
      tolerable surface dose. In addition, we proposed parameters to be studied for the
      optimization of MRT to deep-seated tumors. 

PMID- 24865216
TI  - Phospholipase C-related catalytically inactive protein participates in the
      autophagic elimination of Staphylococcus aureus infecting mouse embryonic
      fibroblasts.
AB  - Autophagy is an intrinsic host defense system that recognizes and eliminates
      invading bacterial pathogens. We have identified microtubule-associated protein 1
      light chain 3 (LC3), a hallmark of autophagy, as a binding partner of
      phospholipase C-related catalytically inactive protein (PRIP) that was originally
      identified as an inositol trisphosphate-binding protein. Here, we investigated
      the involvement of PRIP in the autophagic elimination of Staphylococcus aureus in
      infected mouse embryonic fibroblasts (MEFs). We observed significantly more LC3
      positive autophagosome-like vacuoles enclosing an increased number of S. aureus
      cells in PRIP-deficient MEFs than control MEFs, 3 h and 4.5 h post infection,
      suggesting that S. aureus proliferates in LC3-positive autophagosome-like
      vacuoles in PRIP-deficient MEFs. We performed autophagic flux analysis using an
      mRFP-GFP-tagged LC3 plasmid and found that autophagosome maturation is
      significantly inhibited in PRIP-deficient MEFs. Furthermore, acidification of
      autophagosomes was significantly inhibited in PRIP-deficient MEFs compared to the
      wild-type MEFs, as determined by LysoTracker staining and time-lapse image
      analysis performed using mRFP-GFP-tagged LC3. Taken together, our data show that
      PRIP is required for the fusion of S. aureus-containing autophagosome-like
      vacuoles with lysosomes, indicating that PRIP is a novel modulator in the
      regulation of the innate immune system in non-professional phagocytic host cells.

PMID- 24865217
TI  - Connexin hemichannel blockade is neuroprotective after asphyxia in preterm fetal
      sheep.
AB  - Asphyxia around the time of preterm birth is associated with neurodevelopmental
      disability. In this study, we tested the hypothesis that blockade of connexin
      hemichannels would improve recovery of brain activity and reduce cell loss after
      asphyxia in preterm fetal sheep. Asphyxia was induced by 25 min of complete
      umbilical cord occlusion in preterm fetal sheep (103-104 d gestational age).
      Connexin hemichannels were blocked by intracerebroventricular infusion of mimetic
      peptide starting 90 min after asphyxia at a concentration of 50 uM/h for one hour
      followed by 50 uM/24 hour for 24 hours (occlusion-peptide group, n = 6) or
      vehicle infusion for controls (occlusion-vehicle group, n = 7). Peptide infusion
      was associated with earlier recovery of electroencephalographic power after
      asphyxia compared to occlusion-vehicle (p<0.05), with reduced neuronal loss in
      the caudate and putamen (p<0.05), but not in the hippocampus. In the intragyral
      and periventricular white matter, peptide administration was associated with an
      increase in total oligodendrocyte numbers (p<0.05) and immature/mature
      oligodendrocytes compared to occlusion-vehicle (p<0.05), with a significant
      increase in proliferation (p<0.05). Connexin hemichannel blockade was
      neuroprotective and reduced oligodendrocyte death and improved recovery of
      oligodendrocyte maturation in preterm fetuses after asphyxia. 

PMID- 24865219
TI  - Bridging the gap between financial distress and available resources for patients
      with cancer: a qualitative study.
AB  - PURPOSE: Cancer treatment-related out-of-pocket costs create substantial
      financial distress for many patients. However, little work has been done to
      describe available financial resources and barriers to connecting those resources
      to patients. METHODS: This was a single-center, qualitative study that used
      semistructured interviews and focus groups with social workers and financial care
      counselors. Interview guides were used to elicit feedback from study participants
      pertaining to the types of financial problems that their patients were
      experiencing, the process for addressing these issues, patient assistance
      resources, and access barriers. RESULTS: Four interviews and two focus group
      sessions (n = 15) were conducted in which four themes emerged among the social
      work and financial care counselor samples. Participants cited (1) frustration
      over the lack of financial resources and increasingly stringent eligibility
      criteria, (2) barriers to providing assistance such as process inefficiencies,
      (3) limited resources to identify at- risk patients and refer them for services,
      and (4) inadequate insurance coverage and availability. To bridge the gap between
      increasing patient need and limited resources, participants suggested development
      of interventions designed to aid in patient screening and resource
      identification. CONCLUSIONS: Oncology social workers and financial care
      counselors reported inadequate financial resources and faced barriers to matching
      appropriate resources with patients in need. Limited social work resources
      hindered early screening for financial distress. Interventions that focus on
      screening for early identification of financial distress and identification of
      resources are needed.

PMID- 24865218
TI  - Mesodiencephalic dopaminergic neuronal differentiation does not involve GLI2A
      mediated SHH-signaling and is under the direct influence of canonical WNT
      signaling.
AB  - Sonic Hedgehog (SHH) and WNT proteins are key regulators in many developmental
      processes, like embryonic patterning and brain development. In the brain, SHH is
      expressed in a gradient starting in the floor plate (FP) progressing ventrally in
      the midbrain, where it is thought to be involved in the development and
      specification of mesodiencephalic dopaminergic (mdDA) neurons. GLI2A-mediated SHH
      signaling induces the expression of Gli1, which is inhibited when cells start
      expressing SHH themselves. To determine whether mdDA neurons receive GLI2A
      mediated SHH-signaling during differentiation, we used a BAC-transgenic mouse
      model expressing eGFP under the control of the Gli1 promoter. This mouse-model
      allowed for mapping of GLI2A-mediated SHH-signaling temporal and spatial in the
      mouse midbrain. Since mdDA neurons are born from E10.5, peaking at E11.0-E12.0,
      we examined Gli1-eGFP embryos at E11.5, E12.5, and E13.5, indicating whether Gli1
      was induced before or during mdDA development and differentiation. Our data
      indicate that GLI2A-mediated SHH-signaling is not involved in mdDA neuronal
      differentiation. However, it appears to be involved in the differentiation of
      neurons which make up a subset of the red nucleus (RN). In order to detect
      whether mdDA neuronal differentiation may be under the control of canonical WNT
      signaling, we used a transgenic mouse-line expressing LacZ under the influence of
      stable beta-catenin. Here, we show that TH+ neurons of the midbrain receive
      canonical WNT-signaling during differentiation. Therefore, we suggest that early
      SHH-signaling is indirectly involved in mdDA development through early patterning
      of the midbrain area, whereas canonical WNT-signaling is directly involved in the
      differentiation of the mdDA neuronal population. 

PMID- 24865220
TI  - Impact of financial burden of cancer on survivors' quality of life.
AB  - PURPOSE: Little is known about the relationship between the financial burden of
      cancer and the physical and emotional health of cancer survivors. We examined the
      association between financial problems caused by cancer and reported quality of
      life in a population-based sample of patients with cancer. METHODS: Data from the
      2010 National Health Interview Survey (NHIS) were analyzed. A multivariable
      regression model was used to examine the relationship between the degree to which
      cancer caused financial problems and the patients' reported quality of life.
      RESULTS: Of 2,108 patients who answered the survey question, "To what degree has
      cancer caused financial problems for you and your family?," 8.6% reported "a
      lot," whereas 69.6% reported "not at all." Patients who reported "a lot" of
      financial problems as a result of cancer care costs were more likely to rate
      their physical health (18.6% v 4.3%, P < .001), mental health (8.3% v 1.8%, P <
      .001), and satisfaction with social activities and relationships (11.8% v 3.6%, P
      < .001) as poor compared to those with no financial hardship. On multivariable
      analysis controlling for all of the significant covariates on bivariate analysis,
      the degree to which cancer caused financial problems was the strongest
      independent predictor of quality of life. Patients who reported that cancer
      caused "a lot" of financial problems were four times less likely to rate their
      quality of life as "excellent," "very good," or "good" (odds ratio = 0.24; 95%
      CI, 0.14 to 0.40; P < .001). CONCLUSION: Increased financial burden asa result of
      cancer care costs is the strongest independent predictor of poor quality of life
      among cancer survivors.

PMID- 24865223
TI  - Toehold-mediated DNA logic gates based on host-guest DNA-GNPs.
AB  - A simple, toehold-mediated two-way input DNA machine has been developed.
      Utilizing symmetric and asymmetric protector sequences, INH, XOR logic gates and
      a half-subtractor are designed based on this two-way structure. 

PMID- 24865224
TI  - Preparation of a "twisted basket" Mn(4)N(8) cluster: a two-hydrogen-atom reduced
      analogue of the Mn(4)N(8) pinned butterfly.
AB  - Mn4(MU-NHPh)4(MU-PhNNPh-kappa(2)N,N')2(py)4 () is synthesized via self assembly
      from dimeric Mn2(MU-NHPh)2(NR2)2 and PhNHNHPh (R = SiMe3). This cluster
      represents the N-N cleaved version of the previously-reported Mn4(MU-NHPh)2(MU3
      PhNNPh-kappa(3)N,N')2(MU-PhNNPh-kappa(2)N,N')(py)4 "pinned butterfly" cluster (),
      formally reduced by two hydrogen atoms. Cluster may be converted to by addition
      of N,N'-diphenylhydrazine as a two-electron reductant. 

PMID- 24865226
TI  - Low temperature synthesis of ionic phosphates in dimethyl sulfoxide.
AB  - A new synthesis route for phosphates in an organic solvent at low temperatures is
      presented. The synthesis was done by dispersing a nitrate salt and phosphorus
      pentoxide in dimethyl sulfoxide. The synthesis can be performed under water-free
      conditions and yielded several organic and inorganic phosphates. Crystal
      structure solution of bistetramethylammonium hydrogencyclotriphosphate,
      [N(CH3)4]2HP3O9, was achieved by combining information gained from powder X-ray
      diffraction, liquid NMR and solid state (2D) NMR. The molecular structure of
      rubidium cyclotetraphosphate, Rb4P4O12, was determined using liquid state NMR and
      solid state (2D) NMR spectroscopy. 

PMID- 24865221
TI  - Changes in polysialic acid expression on myeloid cells during differentiation and
      recruitment to sites of inflammation: role in phagocytosis.
AB  - Polysialic acid (polySia) is a unique linear homopolymer of alpha2,8-linked
      sialic acid that has been studied extensively as a posttranslational modification
      of neural cell adhesion molecule in the central nervous system. Only two proteins
      are known to be polysialylated in cells of the immune system: CD56 on human
      natural killer cells and murine bone marrow (BM) leukocytes, and neuropilin-2
      (NRP-2) on dendritic cells (DCs). We tested the hypothesis that polySia
      expression is regulated during maturation and migration of leukocytes and plays a
      role in functional activity. Using wild-type and NCAM(-/-) mice, we show that BM
      neutrophils express only polysialylated CD56, whereas a subset of BM monocytes
      expresses polysialylated CD56 and/or another polysialylated protein(s). We
      demonstrate that polysialylated CD56 expression is progressively down-regulated
      in wild-type monocytes and monocyte-derived cells during migration from BM
      through peripheral blood to pulmonary and peritoneal sites of inflammation.
      Freshly isolated monocyte-derived peritoneal macrophages are devoid of polySia
      yet re-express polySia on NRP-2 and an additional protein(s) after maintenance in
      culture. Removal of polySia from these cells enhances phagocytosis of Klebsiella
      pneumoniae, suggesting that down-regulation of polySia on macrophages facilitates
      bacterial clearance. Using wild-type and NRP-2(-/-) mice, we demonstrate that NRP
      2 and an additional protein(s) are polysialylated by ST8 SiaIV in BM-derived DCs.
      We conclude that polySia expression in monocyte-derived cells is dynamically
      regulated by ST8 SiaIV activity and by expression of carrier proteins during
      recruitment to sites of inflammation and influences cellular interactions with
      microbes, contributing to innate and adaptive immune responses. 

PMID- 24865227
TI  - Seasonal monitoring for Drosophila suzukii (Diptera: Drosophilidae) in California
      commercial raspberries.
AB  - Native to Southeast Asia, Drosophila suzukii (Matsumura) prefer to oviposit on
      ripe fruit and have become an important pest of California raspberries (Rubus
      idaeus L.) since their detection in Santa Cruz County, CA, in 2008. Preliminary
      management guidelines included D. suzukii monitoring recommendations, though
      there was little available information on seasonal occurrence and potential lures
      for use in raspberries. To address this issue, we trapped adult D. suzukii weekly
      for 2 yr (including both spring and fall harvests) in multiple raspberry
      varieties using apple cider vinegar and a yeast-sugar-water mixture as liquid
      lures, and measured fruit infestation when commercially ripe fruit were
      available. D. suzukii pressure as measured by larval infestation and adult trap
      captures was higher during the fall raspberry harvest season. The yeast lure
      captured significantly more D. suzukii during the fall harvest than the apple
      cider vinegar, and while both lures tended to capture more females than males,
      this varied by month of the year and was more pronounced for the yeast lure. Trap
      captures from each lure correlated well to one another, and often exhibited
      significant correlation to larval infestation. However, during all seasons and
      under both conventional and organic management, worrisome outliers were present
      (high larval infestation with low trap captures) that call into question the
      reliability of using the systems presented here as a basis for management
      decisions at this time. 

PMID- 24865228
TI  - Tools for chemical synthesis in microsystems.
AB  - Chemical synthesis in microsystems has evolved from simple proof-of-principle
      examples to become a general technique in academia and industry. Numerous such
      "flow chemistry" applications are now found in pharmaceutical and fine chemical
      synthesis. Much of the development has been based on systems employing
      macroscopic flow components and tubes, rather than the integrated chip technology
      envisioned by the lab-on-a-chip community. We review the major developments in
      systems for flow chemistry and discuss limitations underlying the development of
      chip-scale integrated systems. 

PMID- 24865234
TI  - Molecular characterization and expression of cyp19a gene in Carassius auratus.
AB  - A cyp19a gene that contains nine exons and eight introns was identified from
      Carassius auratus and was mainly expressed in the ovary. The cyp19a mRNA level
      after hatching was initially low, but began to increase from 25 days after
      hatching. A number of cis-acting elements, such as the oestrogen receptor,
      steroidogenic factor 1 and SOX-5 recognition sites, were found in the promoter of
      the cyp19 gene, which possesses a promoter function confirmed by a recombination
      green fluorescent protein checking system in vitro. 

PMID- 24865235
TI  - Pleuroscopy in 'Idiopathic' eosinophilic pleural effusions.
AB  - BACKGROUND: Idiopathic eosinophilic pleural effusions (IEPEs) comprise the
      eosinophilic pleural effusions for which a specific aetiology cannot be
      established. There are no reports investigating IEPE on the basis of a
      systematically applied pleuroscopy approach and entailing an appropriate patient
      follow-up till the final outcome is established; existing series rather combine
      clinical and thoracocentesis criteria to establish the idiopathic character of
      the diagnosis. OBJECTIVES: The aim of our study was to assess the clinical
      outcome of patients with IEPE, who underwent a systematic diagnostic approach by
      pleuroscopy. METHODS: We studied 10 patients with IEPE among 175 consecutive
      patients who underwent pleuroscopy for undiagnosed pleural effusion. Pleural
      biopsies were obtained from observed lesions. All patients were followed up by
      means of clinical examination and imaging. RESULTS: The diagnosis of IEPE was
      established in 10 patients (median age was 50.5 years, range 35-91). Macroscopic
      examination of the pleura showed diffuse thickening with pleural plaques in eight
      patients, consistent with diffuse pleural eosinophilic inflammation
      histologically proven. In two patients, macroscopic examination showed scattered
      nodules associated with non-caseating granulomas histologically. In all 10
      patients, a specific aetiology could not be established. Follow-up was available
      for all patients ranging from 24-102 months (median 60 months). No patient
      received a specific treatment during the follow-up period. No relapse of a
      pleural effusion was documented during this period. CONCLUSION: Pleuroscopy is
      mandatory in diagnosing IEPE. Negative histology and a long follow-up showed a
      benign course. These findings suggest that we should call these effusions
      'indeterminate'.

PMID- 24865240
TI  - A rare cause of recurrent priapism: hereditary angioedema.
AB  - Hereditary angioedema is a rare disease, which is caused by deficiency of
      compleman c1 esterase inhibitor regulatory protein in the compleman system.
      Priapism is involuntary, painful and prolonged erection of penis more than 4 h
      without sexual desire. In this case report, we elucidated a patient diagnosed
      with hereditary angioedema while he had recurrent priapism. 

PMID- 24865238
TI  - BAUS at war.

PMID- 24865236
TI  - The cyclin-dependent kinase inhibitor SNS-032 induces apoptosis in breast cancer
      cells via depletion of Mcl-1 and X-linked inhibitor of apoptosis protein and
      displays antitumor activity in vivo.
AB  - Inhibitors of cyclin-dependent kinases (Cdks) have been reported to have
      activities in many types of cancer cells by inhibiting Cdk7 and Cdk9, which
      control transcription. SNS-032 is a potent and selective inhibitor of Cdk2, Cdk7
      and Cdk9 and has emerged in clinical trials. Here, we examined the viability of
      MCF-7 and MDA-MB-435 breast cancer cells in the presence of SNS-032 and observed
      a dose-dependent inhibition of cellular proliferation in both cell lines. SNS-032
      had a direct apoptosis-inducing effect through both the extrinsic and intrinsic
      apoptotic pathways in breast cancer cells as shown by a dose-dependent increase
      in Annexin V-positive cells and terminal deoxynucleotidyl transferase-mediated
      dUTP nick?end labeling (TUNEL)-positive cells, as well as activation of caspase
      8, -9 and poly(ADP-ribose) polymerase (PARP). At the molecular level, SNS-032
      induced a marked dephosphorylation of serine 2 and 5 of RNA polymerase (RNA Pol)
      II and blocked RNA synthesis. Consistent with the inherently rapid turnover rates
      of their transcripts and proteins, the anti-apoptotic proteins Mcl-1 and X-linked
      inhibitor of apoptosis protein (XIAP) were rapidly reduced on exposure to SNS
      032. Our results also indicated that SNS-032 suppressed the growth of breast
      cancer xenografts in mice. These data demonstrate that the use of SNS-032 may be
      a rational and novel therapeutic strategy for human breast cancer and warrants
      further clinical investigation.

PMID- 24865242
TI  - [Is the validated ICIQ-SF suitable for evaluation of OAB patients? A data
      analysis of intravesicular botulinum toxin therapy].
AB  - BACKGROUND: The following data analysis studied the aspects of patient
      satisfaction following onabotulinum toxin A (BTX-A) treatment including
      modification of certain parameters, such as frequency of micturition and the use
      of pads and in particular, the applicability of the international consultation on
      incontinence questionnaire short form (ICIQ-SF) and the urgency perception scale
      (UPS) in patients with an overactive bladder (OAB). PATIENTS AND METHOD: In this
      study 40 female patients were questioned in the form of validated questionnaires
      (extended ICIQ-SF and UPS) before and after being injected with 300 IU of BTX-A
      in each detrusor muscle. The average age of the patients was 66 years. All
      patients experienced anticholinergic refractory, non-neurogenic OAB. RESULTS: The
      recommendation rate and related patient satisfaction was 82.5 %. A significant
      decrease in the frequency of micturition by 50.9 % (p < 0.01) was reported as
      well as a significant reduction in the use of pads by 66.7 % (p < 0.01). The
      average number of ICIQ-SF points could be significantly (p < 0.01) reduced via
      BTX-A from 15.9 to 7.3. Moreover, BTX-A demonstrated a significant improvement in
      the urgency to urinate, which was illustrated through the UPS. CONCLUSION:
      Treatment with BTX-A achieves significant improvements in female patients with
      anticholinergic refractory OAB with regard to the individual symptoms of OAB
      (e.g. pollakisuria, nocturia, undesired urination and urgency). The use of the
      ICIQ-SF as the only questionnaire in OAB diagnostics proved to be unsuitable as
      it does not include female patients with dry OAB to an adequate degree. A
      combination of various validated questionnaires, such as ICIQ-SF and UPS, proved
      to be useful.

PMID- 24865243
TI  - [Open and minimally invasive partial nephrectomy. Management of complications].
AB  - Current guidelines increasingly recommend organ-preserving surgical procedures in
      the treatment of renal tumors. Both the open surgical and minimally invasive
      surgical techniques are well established. In the literature, various systems for
      the systematic evaluation of comorbidities and complications have been reported.
      Already while taking the patient's history and preoperative planning prior to
      partial nephrectomy, it is recommended that a detailed risk assessment be carried
      out regarding expected complications. Essentially the two critical factors - the
      comorbidities of the patient and anatomic complexity level of the tumor - should
      be evaluated in order to achieve the best possible selection of patients for a
      partial nephrectomy and the determination of the surgical method. 

PMID- 24865244
TI  - MicroRNA-dependent genetic networks during neural development.
AB  - The development of the structurally and functionally diverse mammalian nervous
      system requires the integration of numerous levels of gene regulation.
      Accumulating evidence suggests that microRNAs are key mediators of genetic
      networks during neural development. Importantly, microRNAs are found to regulate
      both feedback and feedforward loops during neural development leading to large
      changes in gene expression. These repressive interactions provide an additional
      mechanism that facilitates the establishment of complexity within the nervous
      system. Here, we review studies that have enabled the identification of microRNAs
      enriched in the brain and discuss the way that genetic networks in neural
      development depend on microRNAs. 

PMID- 24865245
TI  - Developmental regulations of Perp in mice molar morphogenesis.
AB  - Teraspanin transmembrane protein, Perp (P53 apoptosis effector related to PMP22),
      which is found in the plasma membrane as a component of the desmosome, is
      reported to be involved in the morphogenesis of the epithelium and the enamel
      formation of the incisor. However, its expression pattern and signaling
      regulation during molar development have not been elucidated in detail. We have
      examined the precise expression patterns of Perp in developing lower molars and
      employed the knock-down of Perp by antisense oligodeoxynucleotide treatment
      during in vitro organ cultivation at embryonic day 13 to define the precise
      developmental function of Perp. Perp was expressed mainly in the dental lamina
      and stellate reticulum regions at the bud and cap stages. After Perp knock-down,
      the tooth germ showed disruption of the dental lamina and stellate reticulum with
      altered apoptosis and proliferation. The changed expression levels of related
      signaling molecules from the enamel knot and desmosome were evaluated by real
      time quantitative polymerase chain reaction. A renal capsule transplantation
      method was employed to examine the effects of Perp knock-down on molar crown
      development. Ultrastructural observations revealed that enamel was deposited more
      densely in an irregular pattern in the cusp region, and that dentin was hypo
      mineralized after Perp knock-down at the cap stage. Thus, Perp might play
      important roles in the formation and integration of stellate reticulum, dental
      lamina structure and enamel formation through signaling interactions with the
      enamel knot and desmosome-related signaling molecules at the cap stage of lower
      molar development. 

PMID- 24865246
TI  - Photic stimulation of the suprachiasmatic nucleus via the non-visual optic
      system. A gene expression study in the blind Crx-/- mouse.
AB  - The visual system of vertebrates consists of an image-forming and a non-image
      forming optic system; the image-forming optic system involves the classic
      photoreceptors, the rods and cones, whereas the non-image-forming optic system
      involves the melanopsin-containing retinal ganglion cells. Both optic systems
      make direct neuroanatomical connections to the suprachiasmatic nucleus (SCN) in
      the hypothalamus in which the biological clock of vertebrates is located. The
      rhythmic output from SCN neurons is entrained by light via the retina and the
      retinohypothalamic tract. The response of exposure to light during the subjective
      night is an immediate expression of several early response genes in the SCN. We
      show, by quantitative real-time polymerase chain reaction, that the amount of
      melanopsin mRNA in the retinal ganglion cells is preserved in the blind Crx(-/-)
      mouse with degenerated classic photoreceptors. At zeitgeber time 16, the Crx(-/-)
      and wild-type mice were exposed to 1 h of light. This resulted in a strong up
      regulation of the immediate early genes Nr4a1, Erg, and Rrad in the SCN of both
      genotypes. Light stimulation during the subjective night resulted in a strong up
      regulation of c-fos in both genotypes with a significantly higher up-regulation
      in the blind Crx(-/-) mouse. Expression of Grp and Vip, the genes for two classic
      peptides located in the SCN, was not influenced by light stimulation. The data
      strongly indicate the involvement of the melanopsin-based non-visual optic system
      in the regulation of immediate early genes in the SCN.

PMID- 24865248
TI  - Laboratory evaluation of different agar media for isolation of carbapenem
      resistant Acinetobacter spp.
AB  - The optimal method for surveillance of carbapenem-resistant Acinetobacter spp.
      (CRAB) is unknown. A collection of CRAB strains (n = 42), carbapenem-susceptible
      strains (CSAB), and non-Acinetobacter strains (n = 18) was used to evaluate six
      laboratory surveillance methods: MacConkey (MAC), MAC + 1 MUg/ml imipenem (MAC
      IPM), minimal salts agar + 1 % acetate (MSA), MSA with IPM disk (MSA-IPM),
      CHROMagarKPC, and CHROMagar Acinetobacter with CR102 (CHROMAcineto). CHROMAcineto
      was 100 % sensitive and specific. CHROMagarKPC and MAC-IPM were highly sensitive
      (>95 %), but their specificity was substantially hampered by the breakthrough
      growth of CSAB. MSA was unsuitable for CRAB detection. CHROMAcineto is a
      promising medium for CRAB detection and warrants further clinical evaluation.

PMID- 24865253
TI  - Nanostructured biomaterials from electrospun demineralized bone matrix: a survey
      of processing and crosslinking strategies.
AB  - In the design of scaffolds for tissue engineering biochemical function and
      nanoscale features are of particular interest. Natural polymers provide a wealth
      of biochemical function, but do not have the processability of synthetic
      polymers, limiting their ability to mimic the hierarchy of structures in the
      natural extracellular matrix. Thus, they are often combined with synthetic
      carrier polymers to enable processing. Demineralized bone matrix (DBM), a natural
      polymer, is allograft bone with inorganic material removed. DBM contains the
      protein components of bone, which includes adhesion ligands and osteoinductive
      signals, such as important growth factors. Herein we describe a novel method for
      tuning the nanostructure of DBM through electrospinning without the use of a
      carrier polymer. This work surveys solvents and solvent blends for
      electrospinning DBM. Blends of hexafluoroisopropanol and trifluoroacetic acid are
      studied in detail. The effects of DBM concentration and dissolution time on
      solution viscosity are also reported and correlated to observed differences in
      electrospun fiber morphology. We also present a survey of techniques to stabilize
      the resultant fibers with respect to aqueous environments. Glutaraldehyde vapor
      treatment is successful at maintaining both macroscopic and microscopic structure
      of the electrospun DBM fibers. Finally, we report results from tensile testing of
      stabilized DBM nanofiber mats, and preliminary evaluation of their
      cytocompatibility. The DBM nanofiber mats exhibit good cytocompatibility toward
      human dermal fibroblasts (HDF) in a 4-day culture; neither the electrospun
      solvents nor the cross-linking results in any measurable residual cytotoxicity
      toward HDF. 

PMID- 24865254
TI  - Pharmacophore modeling of nilotinib as an inhibitor of ATP-binding cassette drug
      transporters and BCR-ABL kinase using a three-dimensional quantitative structure
      activity relationship approach.
AB  - Nilotinib (Tasigna) is a tyrosine kinase inhibitor approved by the FDA to treat
      chronic phase chronic myeloid leukemia patients. It is also a transport substrate
      of the ATP-binding cassette (ABC) drug efflux transporters ABCB1 (P-glycoprotein,
      P-gp) and ABCG2 (BCRP), which may have an effect on the pharmacokinetics and
      toxicity of this drug. The goal of this study was to identify pharmacophoric
      features of nilotinib in order to potentially develop specific inhibitors of BCR
      ABL kinase with minimal interactions with ABC drug transporters. Three
      dimensional pharmacophore modeling and quantitative structure-activity
      relationship (QSAR) studies were carried out on a series of nilotinib analogues
      to identify chemical features that contribute to inhibitory activity of nilotinib
      against BCR-ABL kinase activity, P-gp, and ABCG2. Twenty-five derivatives of
      nilotinib were synthesized and were then tested to measure their activity to
      inhibit BCR-ABL kinase and to inhibit the function of ABC drug transporters. A
      set of in vitro experiments including kinase activity and cell-based transport
      assays and photolabeling of P-gp and ABCG2 with a transport substrate, [(125)I]
      iodoarylazido-prazosin (IAAP), were carried out in isolated membranes to evaluate
      the potency of the derivatives to inhibit the function of ABC drug transporters
      and BCR-ABL kinase. Sixteen, fourteen, and ten compounds were selected as QSAR
      data sets, respectively, to generate PHASE v3.1 pharmacophore models for BCR-ABL
      kinase, ABCG2, and P-gp inhibitors. The IC50 values of these derivatives against
      P-gp, ABCG2, or BCR-ABL kinase were used to generate pharmacophore features
      required for optimal interactions with these targets. A seven-point pharmacophore
      (AADDRRR) for BCR-ABL kinase inhibitory activity, a six-point pharmacophore
      (ADHRRR) for ABCG2 inhibitory activity, and a seven-point pharmacophore (AADDRRR)
      for P-gp inhibitory activity were generated. The derived models clearly
      demonstrate high predictive power for test sets of BCR-ABL, ABCG2, and P-gp
      inhibitors. In aggregate, these results should aid in the development of specific
      inhibitors of BCR-ABL kinase that exhibit no or minimal interaction with ABC drug
      transporters. 

PMID- 24865255
TI  - Impact of anti-thymocyte globulin during immunosuppression induction in patients
      with hepatitis C after liver transplantation.
AB  - BACKGROUND: Induction immunosuppression with anti-thymocyte globulin (ATG)
      provides potential benefits after liver transplantation (LT). However, its use in
      patients with LT and hepatitis C (HCV) is controversial. AIM: To evaluate the 1-
      and 2-year patient survival and HCV recurrence rate in patients receiving ATG
      during the induction phase of immunosuppression (IPI) after LT. METHODS: A total
      of 49 patients undergoing their first LT for HCV were randomized to receive ATG
      during IPI. Patient survival and HCV recurrence were determined at 1 and 2 years.
      The frequency of acute cellular rejection (ACR), infections, and neoplasms was
      also evaluated. RESULTS: Twenty-six patients were randomized to receive ATG (Arm
      1) and 23 to standard induction therapy (Arm-2). Those given ATG had lower HCV
      recurrence (26.9 vs 73.9 %, p = 0.001). The 1- and 2-year patient survival rates
      were similar for both arms (p = 0.33). Infections occurred in 46.1 % subjects in
      Arm-1 and 34.7 % in Arm-2 (p = 0.562). There was a greater proportion of fungal
      infections in Arm-1 (19.2 vs 0 %, p = 0.032). CONCLUSIONS: ATG during the IPI was
      associated with lower frequency of recurrence of HCV in patients undergoing LT.
      This, however, did not affect the 1- and 2-year survival and the frequency of
      ACR, infections, or neoplasms.

PMID- 24865258
TI  - Development of a novel filter cartridge system with electropositive granule media
      to concentrate viruses from large volumes of natural surface water.
AB  - Exposure to various infectious viruses in environmental drinking water can
      constitute a public health risk. However, it is difficult to detect viruses in
      water due to their low concentration. In this study, we have developed a novel
      filter cartridge system containing electropositive granule media (EGM). Viruses
      present in large volumes of environmental samples were adsorbed onto the EGM, and
      then recovered by elution and poly(ethylene glycol) (PEG) concentration. To
      evaluate the system's efficiency in viral recovery, poliovirus (PV-1), a
      surrogate for enteric viruses, was used to artificially contaminate river water
      samples which were then assayed by quantitative real-time PCR. To optimize the
      concentration procedure, the eluent type, water flow rate and properties (e.g.,
      pH, bacterial, and viral loads), were evaluated. The highest virus recovery was
      obtained by pumping river water at a flow rate of 300 mL/min and then pushing 3 L
      of an eluent containing 3* broth [1.5% (w/v) NaCl, 3% (w/v) tryptone, 1.5% (w/v)
      beef powder] with 0.05 mol/L glycine through the filter. Using this procedure,
      the recovery efficiencies of PV-1 from 10 to 100 L of spiked river water were up
      to 99%. In addition, this method is virus load and pH dependent. Virus recovery
      was maximal at a load of between 10(3.5) and 10(5.5) TCID50 and a pH ranging from
      5 to 7. The bacterial load in the water has no effect on virus recovery.
      Different types of viruses and surface water were tested to validate the system's
      applicability. Results revealed that the EGM filter cartridge was able to
      concentrate PV-1, human adenoviruses (HAdVs) and noroviruses (HuNoVs) with high
      efficiency from river, lake, and reservoir water. Furthermore, it showed more
      efficient recovery than glass wool and 1MDS filters. These data suggest that this
      system provides rapid and efficient virus recovery from a large volume of natural
      surface water and, as such, could be a useful tool in revealing the presence of
      viruses in surface water. 

PMID- 24865256
TI  - Tauroursodeoxycholic acid attenuates progression of steatohepatitis in mice fed a
      methionine-choline-deficient diet.
AB  - BACKGROUND AND AIM: Endoplasmic reticulum (ER) stress has been implicated in the
      development of nonalcoholic steatohepatitis. A methionine-choline-deficient (MCD)
      diet induces robust ER stress response and steatohepatitis, but the effects of ER
      stress modulation on the course of steatohepatitis remain uncertain. The present
      study evaluated whether reducing ER stress using the chemical chaperone
      tauroursodeoxycholic acid (TUDCA) could limit hepatocyte lipoapoptosis and
      progression of MCD diet-induced steatohepatitis. METHODS: HuH7 cells stably
      transfected with sodium taurocholate cotransporting polypeptide (HuH-Ntcp cells)
      and palmitate (PA) were used. Experimental steatohepatitis was induced in male
      C57BL/6 mice using an MCD diet, and three different doses of TUDCA (500, or 1,000
      mg/kg, once daily; or 500 mg/kg twice daily) were administered by gavage from the
      start of the MCD diet regimen or after 4 weeks. RESULTS: TUDCA reduced PA-induced
      ER stress as manifested by decreased eIF2alpha phosphorylation, XBP1 splicing and
      expression of BiP, ATF4, and CHOP in HuH-Ntcp cells. TUDCA also decreased PA
      induced JNK phosphorylation, Puma up-regulation and Bax activation, which in turn
      suppressed caspase-dependent hepatocyte lipoapoptosis. Mice given TUDCA did not
      show a significant decrease in the intrahepatic triglyceride contents and
      steatosis. However, TUDCA treatment significantly reduced hepatic damage compared
      to controls for both early and late treatment groups. TUDCA treatment reduced the
      expression of ER stress markers and pro-apoptotic proteins, leading to decreased
      apoptosis and oxidative stress. Finally, TUDCA reduced histological fibrosis
      along with the down-regulation of pro-fibrotic gene expression in both early and
      late treatment groups. CONCLUSIONS: These results show that TUDCA attenuates the
      progression of MCD diet-induced steatohepatitis by reducing ER stress.

PMID- 24865260
TI  - An undiagnosed stupor in the acute medical unit: a case of malignant catatonia.

PMID- 24865261
TI  - Measles-induced encephalitis.
AB  - Encephalitis is the most frequent neurological complication of measles virus
      infection. This review examines the pathophysiology of measles infection and the
      presentations, diagnosis and treatment of the four types of measles-induced
      encephalitis including primary measles encephalitis, acute post-measles
      encephalitis, measles inclusion body encephalitis and subacute sclerosing
      panencephalitis. The early symptoms of encephalitis may be non-specific and can
      be mistakenly attributed to a systemic infection leading to a delay in diagnosis.
      This review provides a summary of the symptoms that should cause health care
      workers to suspect measles-induced encephalitis. 

PMID- 24865262
TI  - Hypoxia and fractions: an example of how to uncover this uncommon connection.

PMID- 24865263
TI  - Reversible metronidazole-induced subacute cerebellar syndrome.

PMID- 24865264
TI  - Informed consent in Croatia. A work in progress.
AB  - As Croatia makes the transition from one political system and type of economy to
      another, there are inevitable social and political changes that have a profound
      affect on the healthcare system. This article charts some of the progress of
      change with respect to patients' rights and informed consent.

PMID- 24865265
TI  - Thioperoxide-mediated activation of thioglycoside donors.
AB  - Thioperoxide (1) in combination with trimethylsilyl trifluoromethanesulfonate
      (TMSOTf) provides a powerful thiophilic promoter system, capable of activating
      different thioglycosides. Both armed and disarmed thioglycosides were activated
      effectively in the presence of different glycosyl acceptors, giving glycosidation
      products in high to excellent yields. A plausible activation pathway was also
      proposed and supported by isolating side-products trifluoromethylphenyl disulfide
      (CF3SSPh) and alkene (42). 

PMID- 24865267
TI  - Positive prognostication from median-nerve somatosensory evoked cortical
      potentials.
AB  - BACKGROUND: The bilateral absence of the cortical N20 median-nerve somatosensory
      evoked potential (SSEP) is a strong predictor of poor outcome from coma. However,
      when N20s are present, accurate prognostication is challenging. Here, we
      investigated the potential for later SSEP components to help disambiguate outcome
      in these cases. METHODS: In a retrospective review of data from two intensive
      care units, the amplitudes and latencies of the N20, P25, and N35 components of
      28 patients in coma were quantified and related to outcome at discharge from
      primary care (average 1-month post-injury). Only patients who had survived
      primary care were included in order to avoid self-fulfilling prophecies, and to
      focus outcome prediction on those patients with relatively present SSEPs.
      RESULTS: The amplitudes of the N20 and N35 components (averaged across
      hemispheres) significantly predicted the range of outcomes beyond death. Abnormal
      amplitudes of the N20 and N35--as derived from a healthy control group--were
      significantly associated with poor outcome. The relative latencies of the
      cortical components were not related to outcome. CONCLUSIONS: While it is well
      documented that absent SSEPs are highly predictive of poor outcome, the current
      data indicate that the relative preservation (absolute amplitude) of "present"
      N20 and N35 SSEP components can also provide predictive value and thereby inform
      clinicians and families with decision-making in coma. Further prospective study
      will elucidate the relative contributions of etiology to the predictive power of
      these SSEP measures.

PMID- 24865266
TI  - Effect of triple-h prophylaxis on global end-diastolic volume and clinical
      outcomes in patients with aneurysmal subarachnoid hemorrhage.
AB  - BACKGROUND: Although prophylactic triple-H therapy has been used in a number of
      institutions globally to prevent delayed cerebral ischemia (DCI) after
      subarachnoid hemorrhage (SAH), limited evidence is available for the
      effectiveness of triple-H therapy on hemodynamic variables. Recent studies have
      suggested an association between low global end-diastolic volume index (GEDI),
      measured using a transpulmonary thermodilution method, and DCI onset. The current
      study aimed at assessing the effects of prophylactic triple-H therapy on GEDI.
      METHODS: This prospective multicenter study included aneurysmal SAH patients
      admitted to 9 hospitals in Japan. The decision to administer prophylactic triple
      H therapy and the management protocols were left to the physician in charge
      (physician-directed therapy) of each participating institution. The primary
      endpoints were the changes in the hemodynamic variables as analyzed using a
      generalized linear mixed model. RESULTS: Of 178 patients, 62 (34.8 %) received
      prophylactic triple-H therapy and 116 (65.2 %) did not. DCI was observed in 35
      patients (19.7 %), with no significant difference between the two groups [15
      (24.2 %) vs. 20 (17.2 %), p = 0.27]. Although a greater amount of fluid (p <
      0.001) and a higher mean arterial pressure (p = 0.005) were observed in the
      triple-H group, no significant difference was observed between the groups in GEDI
      (p = 0.81) or cardiac output (p = 0.62). CONCLUSIONS: Physician-directed
      prophylactic triple-H administration was not associated with improved clinical
      outcomes or quantitative hemodynamic indicators for intravascular volume.
      Further, GEDI-directed intervention studies are warranted to better define
      management algorithms for SAH patients with the aim of preventing DCI.

PMID- 24865268
TI  - Variability in brain death determination in europe: looking for a solution.
AB  - BACKGROUND: Criteria for determining brain death (BD) vary between countries. We
      report the results of an investigation designed to compare procedures to
      determine BD in different European countries. METHODS: We developed a web-based
      questionnaire that was sent to representatives of 33 European countries.
      Responses were reviewed, and individual respondents were contacted if
      clarification was required. RESULTS: Responses were received from 28 (85 %) of
      the 33 countries to which the questionnaire was sent. Each country has either a
      law (93 %) or national guidance (89 %) for defining BD. Clinical examination is
      sufficient to determine BD in 50 % of countries; coma, apnea, absence of corneal,
      and cough reflexes are mandatory criteria in all. Confirmation of apnea is
      required in all countries but not defined in 4 (14 %). In the 24 (86 %) of
      countries with a formal definition of the apnea test, a target pCO2 level (23/24,
      96 %) is the pre-specified end point in most. The (median, range) number of
      clinical examinations (2, 1-3) and minimum observation time between tests (3 h, 0
      12 h) vary greatly between countries. Additional (confirmatory) tests are
      required in 50 % of countries. Hypothermia (4 %), anoxic injury (7 %), inability
      to complete clinical examination (61 %), toxic drug levels (57 %), and
      inconclusive apnea test (54 %) are among the most common indications for
      confirmatory tests. Cerebral blood flow (CBF) investigation is mandatory in 18 %
      of countries, but optional or indicated only in selected cases in 82 %.
      Conventional angiography is the preferred method of determining absent CBF (50
      %), followed by transcranial Doppler sonography (43 %), computerized tomography
      (CT) angiography (39 %), CT perfusion, and magnetic resonance imaging (MRI)
      angiography (11 %). Electroencephalography is always (21 %) or optionally (14 %)
      recorded. CONCLUSIONS: Although legislation or professional guidance is available
      to standardize nationally the BD diagnosis process in all European countries,
      there are still disparities between countries. The current variation in practice
      makes an international consensus for the definition of BD imperative.

PMID- 24865269
TI  - Neurologist versus machine: is the pupillometer better than the naked eye in
      detecting pupillary reactivity.
AB  - BACKGROUND: A 62-year-old man with severe traumatic brain injury developed
      postsurgical anisocoria in which there was a discrepancy between pupillometer and
      manual testing. METHODS: Case report. RESULTS: The patient's larger pupil was
      read as unreactive by the pupillometer but constricted 1 mm over 7-9 s of
      continuous light stimulation. CONCLUSIONS: While pupillometry assessment is a
      valuable adjunct to the manual pupillary assessment, this case demonstrates that
      nonreactive pupils read on the pupillometer should be confirmed with the manual
      examination because it can miss very slowly reacting pupils.

PMID- 24865270
TI  - Effect of prolonged therapeutic hypothermia on intracranial pressure, organ
      function, and hospital outcomes among patients with aneurysmal subarachnoid
      hemorrhage.
AB  - BACKGROUND: Global cerebral edema (GCE) with subsequent refractory intracranial
      hypertension complicates some cases of aneurysmal subarachnoid hemorrhage (aSAH),
      and typically is associated with poorer outcome. Treatment options for refractory
      intracranial pressure (ICP) cases are limited to decompressive hemicraniectomy
      (DHC) and targeted temperature management (TTM) with induced hypothermia (32-34 
      degrees C). No outcomes comparison between patients treated with either or both
      forms of refractory ICP therapy exists, and data on the effect of prolonged
      hypothermia on ICP and organ function among patients with aSAH are limited.
      METHODS: This is a retrospective study of aSAH patients who underwent DHC and/or
      prolonged hypothermia (greater than 48 h) for refractory ICP (i.e., ICP >20 mmHg
      after osmotherapy) in the intensive care unit of a single, tertiary-care academic
      center. RESULTS: Nineteen individuals with aSAH underwent TTM with or without
      DHC; sixteen patients underwent DHC alone. The patients in TTM group were younger
      (median age 44 years) than the DHC without TTM population (median age 60 years).
      TTM was started on median day 2 with a median duration of 7 days. There were no
      significant group differences in survival to discharge (59 % vs. 69 %) or in the
      mean modified Rankin score on follow-up (3.6 vs. 3.7), despite the TTM group
      having longer hospital length of stay (24 vs. 19 days, p = 0.03), longer duration
      of mechanical ventilation (20 vs. 9 days, p = 0.04), a higher cumulative fluid
      balance (12.8 vs. 5.1 L, p = 0.01), and higher APACHEII scores. The median
      maximal ICP decreased from 23.5 to 21 mmHg within 24 h of hypothermia initiation.
      There were no significant differences in other markers of end-organ function
      (respiratory, hematologic, renal, liver, and cardiac), infection rate, or adverse
      events between groups. CONCLUSIONS: Use of prolonged TTM among aSAH patients with
      GCE and refractory ICP elevations is associated with a longer duration of
      mechanical ventilation but is not different in terms of neurological outcomes
      measured by modified Rankin score or organ function outcomes compared to patients
      who received DHC alone.

PMID- 24865271
TI  - The Subarachnoid Hemorrhage International Trialists (SAHIT) Repository: advancing
      clinical research in subarachnoid hemorrhage.
AB  - Researchers and other stakeholders continue to express concern about the failure
      of randomized clinical trials (RCT) in subarachnoid hemorrhage (SAH) to show
      efficacy of new treatments. Pooled data may be particularly useful to generate
      hypotheses about causes of poor outcomes and reasons for failure of RCT in SAH,
      and strategies to improve them. Investigators conducting SAH research
      collaborated to share data with the intent to develop a large repository of
      pooled individual patient data for exploratory analysis and testing of new
      hypotheses relevant to improved trial design and analysis in SAH. This repository
      currently contains information on 11,443 SAH patients from 14 clinical databases,
      of which 9 are datasets of recent RCTs and 5 are datasets of prospective
      observational studies and hospital registries. Most patients were managed in the
      last 15 years. Data validation and quality checks have been conducted and are
      satisfactory. Data is available on demographic, clinical, neuroimaging, and
      laboratory results and various outcome measures. We have compiled the largest
      known dataset of patients with SAH. The SAHIT repository may be an important
      resource for advancing clinical research in SAH and will benefit from
      contributions of additional datasets. 

PMID- 24865274
TI  - Distribution and histopathological changes induced by cysts of Taenia solium in
      the brain of pigs from Tanzania.
AB  - Neurocysticercosis (NCC) caused by Taenia solium cysts is a frequent but
      neglected parasitic disease of the central nervous system (CNS) worldwide. The
      aim of this study was to describe anatomical locations of cysts in the CNS and
      the corresponding inflammation. A total of 17 naturally infected pigs were used
      to evaluate the distribution of cysts and, of these, seven were used to evaluate
      the corresponding inflammation further, through histopathology. Clinical signs in
      the pigs included dullness, sluggishness, somnolence, apathy and loss of
      consciousness. Cysts were distributed in all cerebral lobes, i.e. 39.7% in the
      frontal lobe, 20.3% in the parietal lobe, 20.0% in the occipital lobe and 19.7%
      in the temporal lobe, and only 0.4% in the cerebellum. No cysts were found in the
      spinal cord. Cysts were localized as follows: 47.9% in the dorsal subarachnoid,
      46.9% in the parenchyma, 4.4% in the subarachnoid base and 0.9% in the
      ventricles. The results of the histopathology revealed lesions in an early
      inflammatory stage, i.e. stage I, in all anatomical locations except for two,
      which showed more of an inflammatory reaction, stage III, in one pig. It was
      concluded that clinical signs in pigs were neither pathognomonic nor consistent.
      These signs, therefore, cannot be used as a reliable indicator of porcine NCC.
      Furthermore, T. solium cysts were found to be in abundance in all cerebral lobes,
      and only a few were found in the cerebellum. Regarding the inflammatory response,
      no significant differences were found in the location and total number of cysts.
      Thus, further studies are needed to explain the determinants of cyst distribution
      in the CNS and assess in detail clinical signs associated with porcine NCC. 

PMID- 24865273
TI  - The FOUR score predicts mortality, endotracheal intubation and ICU length of stay
      after traumatic brain injury.
AB  - BACKGROUND: The Glasgow Coma Scale (GCS) is the most widely accepted scale for
      assessing levels of consciousness, clinical status, as well as prognosis of
      traumatic brain injury (TBI) patients. The Full Outline of UnResponsiveness
      (FOUR) score is a new coma scale developed addressing the limitations of the GCS.
      The aim of this prospective cohort study was to compare the performance of the
      FOUR score vs. the GCS in predicting TBI outcomes. METHODS: From April to July
      2011, 60 consecutive adult patients with TBI admitted to the Alexandria Main
      University Hospital intensive care units (ICU) were enrolled in the study. GCS
      and FOUR score were documented on arrival to emergency room. Outcomes were in
      hospital mortality, unfavorable outcome [Glasgow outcome scale extended (GOSE) 1
      4], endotracheal intubation, and ICU length of stay (LOS). RESULTS: Fifteen (25
      %) patients died and 35 (58 %) had unfavorable outcome. When predicting
      mortality, the FOUR score showed significantly higher area under receiver
      operating characteristic curve (AUC) than the GCS score (0.850 vs. 0.796, p =
      0.025). The FOUR score and the GCS score were not different in predicting
      unfavorable outcome (AUC 0.813 vs. 0.779, p = 0.136) and endotracheal intubation
      (AUC 0.961 vs. 0.982, p = 0.06). Both scores were good predictors of ICU LOS (r
      (2) = 0.40 [FOUR score] vs. 0.41 [GCS score]). CONCLUSIONS: The FOUR score was
      superior to the GCS in predicting in-hospital mortality in TBI patients. There
      was no difference between both scores in predicting unfavorable outcome,
      endotracheal intubation, and ICU LOS.

PMID- 24865275
TI  - Larvicidal potential of Asteraceae family endophytic actinomycetes against Culex
      quinquefasciatus mosquito larvae.
AB  - Pakistan is blessed with plants of Asteraceae family with known medicinal
      background used for centuries by Hakims (traditional physicians). Keeping in mind
      the background of their anti-larval potential, a total of 21 endophytic
      actinomycetes were isolated from four Asteraceae plants and screened against the
      first and fourth instar stages of Culex quinquefasciatus Say mosquito larvae. Of
      the 21 isolates, 6 of them gave strong larvicidal activity (80-100% mortality) in
      the screening results and 4 isolates gave a potent larvicidal activity (100%
      mortality) at the fourth instar stage. These isolates belonged to different
      species within the actinomycetes group, namely Streptomyces albovinaceus and
      Streptomyces badius. This communication reports the larvicidal potential of
      endophytic actinomycetes residing within the native Asteraceae plants in
      Pakistan. The study suggests further exploration through large-scale productions
      leading to the identification of the larvicidal compounds. 

PMID- 24865272
TI  - A continuous correlation between intracranial pressure and cerebral blood flow
      velocity reflects cerebral autoregulation impairment during intracranial pressure
      plateau waves.
AB  - BACKGROUND: In the healthy brain, small oscillations in intracranial pressure
      (ICP) occur synchronously with those in cerebral blood volume (CBV),
      cerebrovascular resistance, and consequently cerebral blood flow velocity (CBFV).
      Previous work has shown that the usual synchrony between ICP and CBFV is lost
      during intracranial hypertension. Moreover, a continuously computed measure of
      the ICP/CBFV association (Fix index) was a more sensitive predictor of outcome
      after traumatic brain injury (TBI) than a measure of autoregulation (Mx index).
      In the current study we computed Fix during ICP plateau waves, to observe its
      behavior during a defined period of cerebrovascular vasodilatation. METHODS:
      Twenty-nine recordings of arterial blood pressure (ABP), ICP, and CBFV taken
      during ICP plateau waves were obtained from the Addenbrooke's hospital TBI
      database. Raw data was filtered prior to computing Mx and Fix according to
      previously published methods. Analyzed data was segmented into three phases (pre,
      peak, and post), and a median value of each parameter was stored for analysis.
      RESULTS: ICP increased from a median of 22-44 mmHg before falling to 19 mmHg.
      Both Mx and Fix responded to the increase in ICP, with Mx trending toward +1,
      while Fix trended toward -1. Mx and Fix correlated significantly (Spearman's R = 
      0.89, p < 0.000001), however, Fix spanned a greater range than Mx. A plot of Mx
      and Fix against CPP showed a plateau (Mx) or trough (Fix) consistent with a zone
      of "optimal CPP". CONCLUSIONS: The Fix index can identify complete loss of
      cerebral autoregulation as the point at which the normally positive CBF/CBV
      correlation is reversed. Both CBF and CBV can be monitored noninvasively using
      near-infrared spectroscopy (NIRS), suggesting that a noninvasive method of
      monitoring autoregulation using only NIRS may be possible.

PMID- 24865277
TI  - Bilateral remote cerebellar haemorrhage after spinal surgery: a case study and
      review of the literature.
AB  - BACKGROUND: Remote cerebellar haemorrhage is a rare and unpredictable
      complication after intracranial and spinal surgery, although less frequently
      found in the latter. The physiopathology of this phenomenon has not been
      definitely explained. OBJECTIVES: To describe and discuss the potential
      implications and pathomechanism of a bilateral remote cerebellar haemorrhage case
      after spinal surgery and review the literature related to this rare phenomenon.
      CASE REPORT: A 75 year-old man developed bilateral remote cerebellar haemorrhage
      after a lumbar laminectomy. Brain CT and MRI examinations showed chronic
      bilateral remote cerebellar haemorrhage, right haemoventricle and bilateral
      supratentorial subarachnoid haemorrhage. Subsequently, the patient underwent
      rehabilitation therapy with improvement of symptoms. CONCLUSION: When large
      cerebrospinal fluid loss is observed during spinal surgery, brain imaging study
      should be carried out. The pathogenetic hypothesis of microcirculation vessels
      tearing, the role of previous spinal surgery and of cerebellar atrophy should be
      considered and validated with further investigation.

PMID- 24865276
TI  - AMAP1 as a negative-feedback regulator of nuclear factor-kappaB under
      inflammatory conditions.
AB  - NF-kappaB is a major transcriptional factor regulating many cellular functions
      including inflammation; therefore, its appropriate control is of high importance.
      The detailed mechanism of its activation has been well characterized, but that of
      negative regulation is poorly understood. In this study, we showed AMAP1, an Arf
      GTPase activating protein, as a negative feedback regulator for NF-kappaB by
      binding with IKKbeta, an essential kinase in NF-kappaB signaling. Proteomics
      analysis identified AMAP1 as a binding protein with IKKbeta. Overexpression of
      AMAP1 suppressed NF-kappaB activity by interfering the binding of IKKbeta and
      NEMO, and deletion of AMAP1 augmented NF-kappaB activity. The activation of NF
      kappaB induced translocation of AMAP1 to cytoplasm from cell membrane and
      nucleus, which resulted in augmented interaction of AMAP1 and IKKbeta. These
      results demonstrated a novel role of AMAP1 as a negative feedback regulator of NF
      kappaB, and presented it as a possible target for anti-inflammatory treatments. 

PMID- 24865278
TI  - Autophagy is required and protects against apoptosis during myoblast
      differentiation.
AB  - Several degradative systems assist in formation of multinucleated terminally
      differentiated myotubes. However, the role of autophagy in this process has not
      been examined. GFP-LC3B (light chain 3 beta) puncta, LC3B-II protein and
      LysoTracker fluorescence increased during C2C12 cell differentiation.
      Importantly, accumulation of LC3B-II protein occurred in CQ (chloroquine)-treated
      cells throughout differentiation. Furthermore, BECN1 (beclin 1), ATG7 (autophagy
      related 7) and ATG12-5 protein increased, whereas SQSTM1/p62 (sequestosome 1)
      protein was rapidly reduced during differentiation. A transient decrease in BECN1
      BCL2 association was observed from day 0.5 to 2 of differentiation. Chemical
      inhibition of JNK (c-Jun N-terminal kinase) during differentiation reduced LC3B
      II protein and GFP-LC3B puncta and maintained BECN1-BCL2 association. Inhibition
      of autophagy by 3MA (3-methyladenine) or shRNA against Atg7 (shAtg7) resulted in
      lower myosin heavy chain expression, as well as impaired myoblast fusion and
      differentiation. Interestingly, 3MA treatment during differentiation increased
      transient CASP3 (caspase 3) activation, DNA fragmentation and the percentage of
      apoptotic nuclei. Similarly, shAtg7 cells had increased DNA fragmentation during
      differentiation compared with the controls. Collectively, these data demonstrate
      that autophagy increases and is required during myoblast differentiation.
      Moreover, autophagy protects differentiating myoblasts from apoptotic cell death.

PMID- 24865280
TI  - Melody recognition revisited: influence of melodic Gestalt on the encoding of
      relational pitch information.
AB  - Melody recognition entails the encoding of pitch intervals between successive
      notes. While it has been shown that a whole melodic sequence is better encoded
      than the sum of its constituent intervals, the underlying reasons have remained
      opaque. Here, we compared listeners' accuracy in encoding the relative pitch
      distance between two notes (for example, C, E) of an interval to listeners
      accuracy under the following three modifications: (1) doubling the duration of
      each note (C - E -), (2) repetition of each note (C, C, E, E), and (3) adding a
      preceding note (G, C, E). Repeating (2) or adding an extra note (3) improved
      encoding of relative pitch distance when the melodic sequences were transposed to
      other keys, but lengthening the duration (1) did not improve encoding relative to
      the standard two-note interval sequences. Crucially, encoding accuracy was higher
      with the four-note sequences than with long two-note sequences despite the fact
      that sensory (pitch) information was held constant. We interpret the results to
      show that re-forming the Gestalts of two-note intervals into two-note "melodies"
      results in more accurate encoding of relational pitch information due to a richer
      structural context in which to embed the interval. 

PMID- 24865279
TI  - Generalized outcome-based strategy classification: comparing deterministic and
      probabilistic choice models.
AB  - Model comparisons are a vital tool for disentangling which of several strategies
      a decision maker may have used--that is, which cognitive processes may have
      governed observable choice behavior. However, previous methodological approaches
      have been limited to models (i.e., decision strategies) with deterministic choice
      rules. As such, psychologically plausible choice models--such as evidence
      accumulation and connectionist models--that entail probabilistic choice
      predictions could not be considered appropriately. To overcome this limitation,
      we propose a generalization of Broder and Schiffer's (Journal of Behavioral
      Decision Making, 19, 361-380, 2003) choice-based classification method, relying
      on (1) parametric order constraints in the multinomial processing tree framework
      to implement probabilistic models and (2) minimum description length for model
      comparison. The advantages of the generalized approach are demonstrated through
      recovery simulations and an experiment. In explaining previous methods and our
      generalization, we maintain a nontechnical focus--so as to provide a practical
      guide for comparing both deterministic and probabilistic choice models.

PMID- 24865281
TI  - Temporal expectancy modulates phasic alerting in both detection and
      discrimination tasks.
AB  - The aim of the present study was to investigate whether phasic alerting might be
      modulated by temporal expectancy and to determine the processing stages at which
      this modulation might occur. We manipulated participants' expectancy for the
      target appearance by systematically varying the cue-target stimulus onset
      asynchrony (SOA) distribution in both detection and discrimination tasks. There
      were three temporal expectancy conditions: the non-aging condition in which
      temporal expectancy was eliminated, the aging condition in which temporal
      expectancy increased as SOA increased, and the accelerated-aging condition in
      which temporal expectancy increased more dramatically as SOA increased than in
      the aging condition. We obtained the same pattern of results in both detection
      and discrimination tasks: the onset time of the alerting effect was postponed
      successively across the three temporal expectancy conditions. The present
      findings suggest that the time course of the alerting effect may be modulated by
      temporal expectancy, highlighting the importance of taking account into the
      influence of temporal expectancy in studies involving the time course of
      cognitive processes. Furthermore, since mechanisms underlying the detection and
      discrimination tasks may differ in early processing stages involving perceptual
      analysis and response selection, the same result pattern observed in both tasks
      is consistent with the hypothesis that the modulation of temporal expectancy on
      phasic alerting occurs at late processing stages involving motor preparation. 

PMID- 24865282
TI  - Perceptuo-motor effects of response-distractor compatibility in speech: beyond
      phonemic identity.
AB  - Previous studies have found faster response times in a production task when a
      speaker perceives a distractor syllable that is identical to the syllable they
      are required to produce. No study has found such effects when a response and a
      distractor are not identical but share parameters below the level of the phoneme.
      Results from Experiment 1 show some evidence of a response-time effect of
      response-distractor voicing congruency. Experiment 2 showed a robust effect of
      articulator congruency: perceiving a distractor that has the same articulatory
      organ as that implicated in the planned motor response speeds up response times.
      These results necessitate a more direct and specific formulation of the
      perception-production link than warranted by previous experimental evidence.
      Implications for theories of speech production are also discussed. 

PMID- 24865283
TI  - Employer health incentives: balancing consumerism and coordination.

PMID- 24865284
TI  - Avoiding pitfalls in estimating heritability with the common options approach.
AB  - In many circumstances, heritability estimates are subject to two potentially
      interacting pitfalls: the spatial and the regression to the mean (RTM) fallacies.
      The spatial fallacy occurs when the set of potential movement options differs
      among individuals according to where individuals depart. The RTM fallacy occurs
      when extreme measurements are followed by measurements that are closer to the
      mean. We simulated data from the largest published heritability study of a
      behavioural trait, colony size choice, to examine the operation of the two
      fallacies. We found that spurious heritabilities are generated under a wide range
      of conditions both in experimental and correlative estimates of heritability.
      Classically designed cross-foster experiments can actually increase the frequency
      of spurious heritabilities. Simulations showed that experiments providing all
      individuals with the identical set of options, such as by fostering all offspring
      in the same breeding location, are immune to the two pitfalls. 

PMID- 24865285
TI  - Microdialysis pharmacokinetic study of scopolamine in plasma, olfactory bulb and
      vestibule after intranasal administration.
AB  - The purpose of this study was to investigate the microdialysis pharmacokinetic of
      scopolamine in plasma, olfactory bulb and vestibule after intranasal
      administration. The pharmacokinetic study of subcutaneous and oral administration
      was also performed in rats. From the in vivo results, scopolamine intranasal
      administration can avoid hepatic first-pass effect. Tmax plasma samples after
      intranasal administration were significantly faster than oral administration and
      subcutaneous injection. The relative bioavailability of intranasal
      administrations was 51.8-70% when compared with subcutaneous injection. Moreover,
      one can see that in comparison with scopolamine subcutaneous administration,
      scopolamine intranasal gel and solutions can increased drug target index (DTI)
      with olfactory bulb 1.69 and 2.05, vestibule 1.80 and 2.15, respectively. The
      results indicated that scopolamine can be absorbed directly through the olfactory
      mucosa into the olfactory bulb, and then transported to various brain tissue
      after intranasal administration, with the characteristics of brain drug delivery.

PMID- 24865286
TI  - Peri-tumoral leakage during intra-tumoral convection-enhanced delivery has
      implications for efficacy of peri-tumoral infusion before removal of tumor.
AB  - In cases of malignant brain tumors, infiltrating tumor cells that exist at the
      tumor-surrounding brain tissue always escape from cytoreductive surgery and,
      protected by blood-brain barrier (BBB), survive the adjuvant chemoradiotherapy,
      eventually leading to tumor recurrence. Local interstitial delivery of
      chemotherapeutic agents is a promising strategy to target these cells. During our
      effort to develop effective drug delivery methods by intra-tumoral infusion of
      chemotherapeutic agents, we found consistent pattern of leakage from the tumor.
      Here we describe our findings and propose promising strategy to cover the brain
      tissue surrounding the tumor with therapeutic agents by means of convection
      enhanced delivery. First, the intracranial tumor isograft model was used to
      define patterns of leakage from tumor mass after intra-tumoral infusion of the
      chemotherapeutic agents. Liposomal doxorubicin, although first distributed inside
      the tumor, distributed diffusely into the surrounding normal brain once the
      leakage happen. Trypan blue dye was used to evaluate the distribution pattern of
      peri-tumoral infusions. When infused intra- or peri-tumorally, infusates
      distributed robustly into the tumor border. Subsequently, volume of distributions
      with different infusion scheduling; including intra-tumoral infusion, peri
      tumoral infusion after tumor resection, peri-tumoral infusion without tumor
      removal with or without systemic infusion of steroids, were compared with Evans
      blue dye. Peri-tumoral infusion without tumor removal resulted in maximum volume
      of distribution. Prior use of steroids further increased the volume of
      distribution. Local interstitial drug delivery targeting tumor surrounding brain
      tissue before tumor removal should be more effective when targeting the invading
      cells. 

PMID- 24865287
TI  - Candesartan cilexetil loaded solid lipid nanoparticles for oral delivery:
      characterization, pharmacokinetic and pharmacodynamic evaluation.
AB  - Candesartan cilexetil (CC) is used in the treatment of hypertension and heart
      failure. It has poor aqueous solubility and low oral bioavailability. In this
      work, CC loaded solid lipid nanoparticles (CC-SLNs) were developed to improve the
      oral bioavailability. Components of the SLNs include either of
      trimyristin/tripalmitin/tristearin, and surfactants (Poloxamer 188 and egg
      lecithin E80). The CC loaded nanoparticles were prepared by hot homogenization
      followed by ultrasonication method. The physicochemical properties, morphology of
      CC-SLNs were characterized, the pharmacokinetic and pharmacodynamic behaviour of
      CC-SLNs were evaluated in rats. Stable CC-SLNs having a mean particle size of 180
      220 nm with entrapment efficiency varying in between 91-96% were developed. The
      physical stability of optimized formulation was studied at refrigerated and room
      temperature for 3 months. Further, freeze drying was tried for improving the
      physical stability. DSC and XRD analyses indicated that the drug incorporated
      into SLN was in amorphous form but not in crystalline state. The SLN-morphology
      was found to be nearly spherical by electron microscopic studies. Pharmacokinetic
      results indicated that the oral bioavailability of CC was improved over 2.75-fold
      after incorporation into SLNs. Pharmacodynamic study of SLNs in hypertensive rats
      showed a decrease in systolic blood pressure for 48 h, while suspension showed a
      decrease in systolic blood pressure for only 2 h. Taken together, these effects
      are due to enhanced bioavailability coupled with sustained action of CC in SLN
      formulation. Thus, the results conclusively demonstrated the role of CC-SLNs for
      a significant enhancement in oral bioavailability along with improved
      pharmacodynamic effect. 

PMID- 24865288
TI  - Comparison of active and passive targeting of doxorubicin for somatostatin
      receptor 2 positive tumor models by octreotide-modified HPMA copolymer
      doxorubicin conjugates.
AB  - Somatostatin receptor 2 (SSTR2), specifically over-expressed on many tumor cells,
      is a potential receipt for active targeting in cancer therapy. In the present
      study, octreotide (Oct), which had high affinity to SSTR2, was attached to N-(2
      hydroxypropyl) methacrylamide (HPMA) polymeric system to enhance the antitumor
      efficiency of the anticancer drug doxorubicin (DOX). Two kinds of cell lines
      (HepG2 and A549), which overexpress SSTR2, were chosen as cell models. Compared
      with non-modified conjugates, Oct-modified conjugates exhibited superior
      cytotoxicity and intracellular uptake on both HepG2 and A549 cell lines. This
      might be due to the mechanism of receptor-mediated endocytosis. Subsequently, the
      in vivo biodistribution and antitumor activity evaluations showed that Oct
      modification significantly improved the tumor accumulation and antitumor efficacy
      of HPMA copolymer conjugates in SSTR2 over-expressed Kunming mice bearing H22
      tumor xenografts. In summary, Oct-modified HPMA polymer-DOX conjugates might be a
      promising system for the treatment of SSTR2 over-expressed cancers. 

PMID- 24865289
TI  - Delivery of gatifloxacin using microemulsion as vehicle: formulation, evaluation,
      transcorneal permeation and aqueous humor drug determination.
AB  - The successful ophthalmic delivery system is reliant on the diminution in the
      precorneal loss of drugs by increasing the corneal contact time and increasing
      the transcorneal permeability, which may enhance the bioavailability of drug to
      the eyes. The objective of this investigation was to develop and evaluate the
      potential of microemulsions of gatifloxacin with respect to the conventional eye
      drops of gatifloxacin. Oil-in-water microemulsions were prepared with different
      concentrations of oil, surfactant and co-surfactant using aqueous titration
      method. All formulations showed circular shape droplets, displayed an average
      droplet size ranged between 51 and 74 nm and absolute zeta potential values
      ranged from 15 to 24 mV, with optimum physicochemical characteristics suitable
      for eye. The optimized microemulsion possessed good stability, showed greater
      adherence to corneal surface and good permeation of gatifloxacin in the anterior
      chamber of the eye, resulting in a twofold increase in gatifloxacin concentration
      than the conventional dosage form. Hence, the optimized microemulsions showed
      increased intraocular penetration and enhance ocular bioavailability of
      gatifloxacin. 

PMID- 24865290
TI  - pH-responsive thiolated chitosan nanoparticles for oral low-molecular weight
      heparin delivery: in vitro and in vivo evaluation.
AB  - The aim of present study was to investigate a pH-responsive and mucoadhesive
      nanoparticle system for oral bioavailability enhancement of low-molecular weight
      heparin (LMWH). The thioglycolic acid (TGA) was first covalently attached to
      chitosan (CS) with 396.97 +/- 54.54 MUmol thiol groups per gram of polymer and
      then the nanoparticles were prepared with thiolated chitosan (TCS) and pH
      sensitive polymer hydroxypropyl methylcellulose phthalate (HPMCP) by ionic cross
      linking method. The obtained nanoparticles were characterized for the shape,
      particle size, zeta potential, drug entrapment efficiency and loading capacity.
      In vitro results revealed the acid stability of pH-responsive nanoparticles,
      which had a significant control over LMWH release and could effectively protect
      entrapped drugs in simulated gastric conditions. By the attachment of the thiol
      ligand, an improvement of permeation-enhancing effect on freshly excised carp
      intestine (1.86-fold improvement) could be found. The mucoadhesive properties
      were evaluated using fluorescently labeled TCS or CS nanoparticles. As compared
      with the controls, a significant improvement of mucoadhesion on rat intestinal
      mucosa was observed in TCS/HPMCP nanoparticles via confocal laser scanning
      microscopy. The activated partial thromboplastin time (APTT) was significantly
      prolonged and an increase in the oral bioavailability of LMWH was turned out to
      be pronounced after oral delivered LMWH-loaded TCS/HPMCP nanoparticles in rats,
      which suggested enhanced anticoagulant effects and improved absorption of LMWH.
      In conclusion, pH-responsive TCS/HPMCP nanoparticles hold promise for oral
      delivery of LMWH.

PMID- 24865291
TI  - A study of the dexamethasone sodium phosphate release properties from a
      periocular capsular drug delivery system.
AB  - The aim of this study was to investigate whether a periocular capsular drug
      delivery system (DDS) can release dexamethasone sodium phosphate (DEXP) in vitro
      and in vivo to the posterior segment of rabbit's eye. In vitro, the periocular
      capsular DDS containing 2 mg/ml or 5 mg/ml DEXP was immersed in modified Franz
      diffusion cell. Four-hundred microliters of liquid was aspirated at 0.5, 1, 2, 4,
      8, 24 and 48 h for determination. In vivo, the DEXP-filled periocular capsular
      DDS was implanted into the sub-Tenon's sac of the New Zealand rabbit. DEXP
      concentration at the serum aqueous humor, cornea, iris, lens, ciliary body,
      vitreous, retina, choroids and sclera was quantified at 1, 3, 7, 14, 28 and 56 d
      after implantation. The DEXP concentration was determined by ultra-performance
      liquid chromatography-tandem mass spectrometry. In vitro, the periocular capsular
      DDS released the DEXP in time-dependent manner from 1/2 to 48 h. In vivo, the
      concentrations of the DEXP at the retina, choroids, ciliary body and iris were
      123.11 (91.23, 732.61) ng/g, 362.46 +/- 330.46 ng/g, 71.64 (71.35, 180.21) ng/g
      and 192.50 +/- 42.66 ng/g, respectively, at 56 d after implantation. Minimal DEXP
      was found in the aqueous, serum and vitreous. Our results demonstrated that DEXP
      could be sustained released from the periocular capsular DDS, which indicated
      that the periocular capsular DDS might be a potential candidate of transscleral
      drug delivery for the management of posterior segment diseases. 

PMID- 24865292
TI  - QbD-enabled systematic development of gastroretentive multiple-unit microballoons
      of itopride hydrochloride.
AB  - The objectives of present studies were to develop the systematically optimized
      multiple-unit gastroretentive microballoons, i.e. hollow microspheres of itopride
      hydrochloride (ITH) employing quality by design (QbD)-based approach. Initially,
      the patient-centric QTPP and CQAs were earmarked, and preliminary studies were
      conducted to screen the suitable polymer, solvent, solvent ratio, pH and
      temperature conditions. Microspheres were prepared by non-aqueous solvent
      evaporation method employing Eudragit S-100. Risk assessment studies carried out
      by constructing Ishikawa cause-effect fish-bone diagram, and techniques like risk
      estimation matrix (REM) and failure mode effect analysis (FMEA) facilitated the
      selection of plausible factors affecting the drug product CQAs, i.e. percent
      yield, entrapment efficiency (EE) and percent buoyancy. A 3(3) Box-Behnken design
      (BBD) was employed for optimizing CMAs and CPPs selected during factor screening
      studies employing Taguchi design, i.e. drug-polymer ratio (X1), stirring
      temperature (X2) and stirring speed (X3). The hollow microspheres, as per BBD,
      were evaluated for EE, particle size and drug release characteristics. The
      optimum formulation was embarked upon using numerical desirability function
      yielding excellent floatation characteristics along with adequate drug release
      control. Drug-excipient compatibility studies employing FT-IR, DSC and powder XRD
      revealed absence of significant interaction among the formulation excipients. The
      SEM studies on the optimized formulation showed hollow and spherical nature of
      the prepared microspheres. In vivo X-ray imaging studies in rabbits confirmed the
      buoyant nature of the hollow microspheres for 8 h in the upper GI tract. In a
      nutshell, the current investigations report the successful development of
      gastroretentive floating microspheres for once-a-day administration of ITH. 

PMID- 24865293
TI  - Antioxidant effect of immediate- versus sustained-release melatonin in type 2
      diabetes mellitus and healthy controls.
AB  - Oxidative damage has been suggested as the primary cause of aging and age
      associated diseases including type 2-dependent diabetes mellitus (T2DM) and
      therefore there is a growing interest in exploring therapeutic potential of
      antioxidant agents including melatonin. In the present study, we analyzed red
      blood cell antioxidants and lipid peroxidation after 5 mg/daily immediate-release
      melatonin treatment of elderly T2DM patients and healthy elderly subjects in
      comparison with 2 mg/daily sustained-release melatonin treatment of elderly T2DM
      patients and healthy elderly subjects, to determine the antioxidant effect of
      different doses and formulations of melatonin in these groups. Our study revealed
      that there was no significant difference in antioxidant status of red blood cells
      measured by glutathione concentration and activities of GPx-1, CAT, GR, SOD-1 and
      MDA levels, after supplementation with 2 mg-sustained release melatonin or with 5
      mg-immediate release melatonin, either in T2DM or in healthy elderly subjects.
      These results suggest that both preparations may exert similar therapeutic effect
      related to melatonin's action on antioxidant defense system. 

PMID- 24865294
TI  - Development and characterization of highly selective target-sensitive liposomes
      for the delivery of streptokinase: in vitro/in vivo studies.
AB  - Streptokinase is one of the most commonly used thrombolytic agents for the
      treatment of thromboembolism. Short half-life of the streptokinase requires
      administration of higher dose which results in various side effects including
      systemic haemorrhage due to activation of systemic plasmin. To increase the
      selectivity of the streptokinase and hence to reduce side effects, various novel
      carriers have been developed. Among these carriers, liposomes have been emerged
      as versatile carrier. In the present study, highly selective target-sensitive
      liposomes were developed and evaluated by in vitro and in vivo studies. Prepared
      liposomes were found to release streptokinase in vitro following binding with
      activated platelets. Intravital microscopy studies in thrombosed murine model
      revealed higher accumulation of liposomes in the thrombus area. In vivo
      thrombolysis study was performed in the human clot inoculated rat model. Results
      of the study showed that target-sensitive liposomes dissolved 28.27 +/- 1.56%
      thrombus as compared to 17.18 +/- 1.23% of non-liposomal streptokinase. Further,
      it was also observed that target-sensitive liposomes reduced the clot dissolution
      time as compared to streptokinase solution. Studies concluded that developed
      liposomes might be pragmatic carriers for the treatment of thromboembolism. 

PMID- 24865295
TI  - Paliperidone microemulsion for nose-to-brain targeted drug delivery system:
      pharmacodynamic and pharmacokinetic evaluation.
AB  - OBJECTIVE: The objective of present study was to develop and evaluate
      paliperidone (PALI) loaded microemulsion (PALI-ME) for intranasal delivery in the
      treatment of schizophrenia. MATERIAL AND METHODS: The PALI-ME was formulated by
      the spontaneous microemulsification method and characterized for physicochemical
      parameters. Pharmacodynamic assessments (apomorphine-induced compulsive behavior
      and spontaneous motor activity) were performed using mice. All formulations were
      tagged with (99m)Tc (technetium). Pharmacokinetic evaluation of PALI in the brain
      was investigated using Swiss albino rats. Brain scintigraphy imaging was
      performed in rabbits. RESULTS AND DISCUSSION: PALI-ME was found stable with
      average droplet size of 20.01 +/- 1.28 nm. In pharmacodynamic studies,
      significant (p < 0.05) deference in parameters estimated, were found between the
      treated and control groups. (99m)Tc-tagged PALI solution (PALI-SOL)/PALI-ME/PALI
      muco-adhesive ME (PALI-MME) was found to be stable and suitable for in vivo
      studies. Brain-to-blood ratio at all sampling points up to 8 h following
      intranasal administration of PALI-MME compared to intravenous PALI-ME was found
      to be 6-8 times higher signifying greater extent of distribution of the PALI in
      brain. Rabbit brain scintigraphy demonstrated higher intranasal uptake of the
      PALI into the brain. CONCLUSION: This investigation demonstrates a prompt and
      larger extent of transport of PALI into the brain through intranasal PALI-MME,
      which may prove beneficial for treatment of schizophrenia.

PMID- 24865296
TI  - Optimized sildenafil citrate fast orodissolvable film: a promising formula for
      overcoming the barriers hindering erectile dysfunction treatment.
AB  - Sildenafil citrate, a drug used to treat erectile dysfunction, is available in
      tablet form but has three major problems. First, the drug displays poor aqueous
      solubility, which delays its onset of action. Second, the drug undergoes
      extensive first-pass metabolism, resulting in a low (40%) bioavailability. Third,
      the gastrointestinal effects of sildenafil citrate include dyspepsia and a
      burning sensation. The objective of this study was to prepare sildenafil citrate
      using a fast orodissolvable film (ODF) containing the drug in a solid dispersion
      (SD) to mitigate the abovementioned problems. The solubility of sildenafil
      citrate in beta-cyclodextrin derivatives was estimated, and SDs were prepared and
      characterized. To develop an ODF that disintegrates rapidly and releases the
      maximum amount of sildenafil citrate, a 3(3) Box-Behnken experimental design was
      used to estimate the effects of different concentrations of film forming polymer
      (X1), the film modifier (X2), and the plasticizer (X3) on the responses, i.e. the
      disintegration time (Y1) and the amount of drug released (Y2). Pharmacokinetic
      studies with the optimized (ODF) were conducted on human volunteers. SD prepared
      using hydroxybutyl-beta-cyclodextrin enhanced the solubility of sildenafil
      citrate by more than eightfold. The Y1 for the optimized ODF was 89 seconds, and
      the Y2 was 86%; this formula also exhibited a rapid onset of action, and its
      bioavailability was enhanced by 2.25-fold compared with that of the marketed
      tablet. The ODF is a promising formulation for sildenafil citrate that results in
      higher solubility, a rapid onset of action, and enhanced systemic
      bioavailability. 

PMID- 24865298
TI  - Pharmacogenomics: Current State-of-the-Art.
AB  - The completion of the human genome project 10 years ago was met with great
      optimism for improving drug therapy through personalized medicine approaches,
      with the anticipation that an era of genotype-guided patient prescribing was
      imminent. To some extent this has come to pass and a number of key
      pharmacogenomics markers of inter-individual drug response, for both safety and
      efficacy, have been identified and subsequently been adopted in clinical practice
      as pre-treatment genetic tests. However, the universal application of genetics in
      treatment guidance is still a long way off. This review will highlight important
      pharmacogenomic discoveries which have been facilitated by the human genome
      project and other milestone projects such as the International HapMap and 1000
      genomes, and by the continued development of genotyping and sequencing
      technologies, including rapid point of care pre-treatment genetic testing.
      However, there are still many challenges to implementation for the many other
      reported biomarkers which continue to languish within the discovery phase. As
      technology advances over the next 10 years, and the costs fall, the field will
      see larger genetic data sets, including affordable whole genome sequences, which
      will, it is hoped, improve patient outcomes through better diagnostic, prognostic
      and predictive biomarkers. 

PMID- 24865299
TI  - Pulmonary complications of childhood cancers.
AB  - Pulmonary complications are frequently seen in survivors of childhood cancer, and
      are due to both disease-related and treatment-related causes. While primary lung
      cancer is extremely rare in the pediatric population, the lung is a common site
      for metastatic disease. Furthermore, therapies used to treat the pediatric
      population can often cause pulmonary toxicity. Specifically, chemotherapy,
      radiation, hematopoietic stem cell transplant, and surgery can all cause long
      term damage to the sensitive lung tissue. These pulmonary sequelae can be further
      subdivided into acute and late effects. 

PMID- 24865301
TI  - Can we use electrocochleography as a clinical tool in the diagnosis of Meniere's
      disease during the early symptomatic period?
AB  - CONCLUSION: Our results indicate that electrocochleography (ECoG) has limited
      value in diagnosing Meniere's disease during the early symptomatic period.
      OBJECTIVE: We hypothesized that if endolymphatic hydrops is a cause of Meniere's
      disease, ECoG results obtained in normal subjects would differ from those
      obtained during the early symptomatic period of Meniere's disease. We aimed to
      investigate the usefulness of ECoG in the diagnosis of Meniere's disease during
      the early symptomatic period. METHODS: Extratympanic ECoG was used to evaluate 60
      patients in a Meniere's group (17 men, 43 women; mean age 43.6 years, range 19-62
      years) and 30 controls (11 men, 19 women; mean age 43.5 years, range 21-63
      years). The summating potential/action potential (SP/AP) amplitude ratio and
      SP/AP area ratio were compared between the groups. RESULTS: Statistically
      significant differences were not demonstrated in the SP/AP amplitude ratio
      between the definite Meniere's, probable Meniere's, overall Meniere's, or control
      groups (0.35 +/- 0.02, 0.30 +/- 0.03, 0.33 +/- 0.02, and 0.30 +/- 0.01,
      respectively). Additionally, statistically significant differences were not
      indicated in the mean SP/AP area ratio between the definite Meniere's, probable
      Meniere's, overall Meniere's, or control groups (5.18 +/- 0.98, 4.78 +/- 0.21,
      4.01 +/- 0.78, and 3.72 +/- 0.66, respectively).

PMID- 24865302
TI  - Adaptation of cochlear implant fitting to various telecommunication systems: a
      proposal for a 'telephone map'.
AB  - CONCLUSIONS: Despite the innovations in cochlear implant (CI) technology in
      recent years, some auditory tasks remain difficult for CI recipients. This work
      proposes the creation of specific maps for telephone communication (via
      conventional phone and via Internet protocol, VoIP). In light of our preliminary
      results, we believe that our experimental maps might improve conventional
      telephone and Internet communications for CI recipients. OBJECTIVES: This study
      aimed to: (1) analyze the spectro-temporal characteristics of the signals; (2)
      evaluate speech recognition scores using two different types of telephone
      communication; and (3) change some map parameters on the basis of the previous
      signal analysis, to obtain a specific map for telephone use. METHODS: Eleven
      CochlearTM Nucleus(r) CI recipients were tested for bisyllabic word recognition
      in quiet using reproduced voice and transmitted voice via conventional telephone
      and Skype(r) using the habitual-ACE (SLB) map, and two experimental maps (F- and
      V-Map). RESULTS: The results showed a worsening of word recognition scores with
      SLB-Map via telephone (30.5%) and VoIP (18.6%) compared with those achieved with
      the same map in an anechoic booth. In the experimental listening conditions, 65%
      and 54% of patients performed better with F- and V-Map, respectively, up to a
      maximum of performance improvement by 35% via telephone and 25% via VoIP.

PMID- 24865303
TI  - Pressure support versus T-tube for weaning from mechanical ventilation in adults.
AB  - BACKGROUND: Mechanical ventilation is important in caring for patients with
      critical illness. Clinical complications, increased mortality, and high costs of
      health care are associated with prolonged ventilatory support or premature
      discontinuation of mechanical ventilation. Weaning refers to the process of
      gradually or abruptly withdrawing mechanical ventilation. The weaning process
      begins after partial or complete resolution of the underlying pathophysiology
      precipitating respiratory failure and ends with weaning success (successful
      extubation in intubated patients or permanent withdrawal of ventilatory support
      in tracheostomized patients). OBJECTIVES: To evaluate the effectiveness and
      safety of two strategies, a T-tube and pressure support ventilation, for weaning
      adult patients with respiratory failure that required invasive mechanical
      ventilation for at least 24 hours, measuring weaning success and other clinically
      important outcomes. SEARCH METHODS: We searched the following electronic
      databases: Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane
      Library 2012, Issue 6); MEDLINE (via PubMed) (1966 to June 2012); EMBASE (January
      1980 to June 2012); LILACS (1986 to June 2012); CINAHL (1982 to June 2012);
      SciELO (from 1997 to August 2012); thesis repository of CAPES (Coordenacao de
      Aperfeicoamento de Pessoal de Nivel Superior)
      (http://capesdw.capes.gov.br/capesdw/) (August 2012); and Current Controlled
      Trials (August 2012).We reran the search in December 2013. We will deal with any
      studies of interest when we update the review. SELECTION CRITERIA: We included
      randomized controlled trials (RCTs) that compared a T-tube with pressure support
      (PS) for the conduct of spontaneous breathing trials and as methods of gradual
      weaning of adult patients with respiratory failure of various aetiologies who
      received invasive mechanical ventilation for at least 24 hours. DATA COLLECTION
      AND ANALYSIS: Two authors extracted data and assessed the methodological quality
      of the included studies. Meta-analyses using the random-effects model were
      conducted for nine outcomes. Relative risk (RR) and mean difference (MD) or
      standardized mean difference (SMD) were used to estimate the treatment effect,
      with 95% confidence intervals (CI). MAIN RESULTS: We included nine RCTs with 1208
      patients; 622 patients were randomized to a PS spontaneous breathing trial (SBT)
      and 586 to a T-tube SBT. The studies were classified into three categories of
      weaning: simple, difficult, and prolonged. Four studies placed patients in two
      categories of weaning. Pressure support ventilation (PSV) and a T-tube were used
      directly as SBTs in four studies (844 patients, 69.9% of the sample). In 186
      patients (15.4%) both interventions were used along with gradual weaning from
      mechanical ventilation; the PS was gradually decreased, twice a day, until it was
      minimal and periods with a T-tube were gradually increased to two and eight hours
      for patients with difficult and prolonged weaning. In two studies (14.7% of
      patients) the PS was lowered to 2 to 4 cm H2O and 3 to 5 cm H2O based on
      ventilatory parameters until the minimal PS levels were reached. PS was then
      compared to the trial with the T-tube (TT).We identified 33 different reported
      outcomes in the included studies; we took 14 of them into consideration and
      performed meta-analyses on nine. With regard to the sequence of allocation
      generation, allocation concealment, selective reporting and attrition bias, no
      study presented a high risk of bias. We found no clear evidence of a difference
      between PS and TT for weaning success (RR 1.07, 95% CI 0.97 to 1.17, 9 studies,
      low quality of evidence), intensive care unit (ICU) mortality (RR 0.81, 95% CI
      0.53 to 1.23, 5 studies, low quality of evidence), reintubation (RR 0.92, 95% CI
      0.66 to 1.26, 7 studies, low quality evidence), ICU and long-term weaning unit
      (LWU) length of stay (MD -7.08 days, 95% CI -16.26 to 2.1, 2 studies, low quality
      of evidence) and pneumonia (RR 0.67, 95% CI 0.08 to 5.85, 2 studies, low quality
      of evidence). PS was significantly superior to the TT for successful SBTs (RR
      1.09, 95% CI 1.02 to 1.17, 4 studies, moderate quality of evidence). Four studies
      reported on weaning duration, however we were unable to combined the study data
      because of differences in how the studies presented their data. One study was at
      high risk of other bias and four studies were at high risk for detection bias.
      Three studies reported that the weaning duration was shorter with PS, and in one
      study the duration was shorter in patients with a TT. AUTHORS' CONCLUSIONS: To
      date, we have found evidence of generally low quality from studies comparing
      pressure support ventilation (PSV) and with a T-tube. The effects on weaning
      success, ICU mortality, reintubation, ICU and LWU length of stay, and pneumonia
      were imprecise. However, PSV was more effective than a T-tube for successful
      spontaneous breathing trials (SBTs) among patients with simple weaning. Based on
      the findings of single trials, three studies presented a shorter weaning duration
      in the group undergoing PS SBT, however a fourth study found a shorter weaning
      duration with a T-tube.

PMID- 24865304
TI  - Mucormycosis-induced colon perforation after renal transplantation.

PMID- 24865307
TI  - Discharge patterns, survival outcomes, and changes in clinical management of
      hospitalized adult patients with cancer with a do-not-resuscitate order.
AB  - BACKGROUND: Do-not-resuscitate (DNR) orders prevent medically futile attempts at
      resuscitation but are not always instituted in hospitalized patients with
      advanced cancer. One explanation for this underuse is the perception that DNR
      orders are inevitably associated with withdrawal of all medical interventions and
      inpatient death. OBJECTIVES: To audit discharge and survival outcomes and changes
      in clinical management in hospitalized adult oncology patients with a DNR order,
      allowing an assessment of whether such orders lead to cessation of acute
      interventions and high rates of in-hospital death. METHODS: Retrospective data
      were collected from 270 oncology inpatients at Austin Health, Melbourne,
      Australia, between February 1, 2012 and November 30, 2012. RESULTS: Mean and
      median time to institution of DNR orders after admission were 2.1 and 1.0 days,
      respectively (interquartile range, 0-2 days). Medical interventions continued in
      80% or more of cases after DNR orders were placed included blood draws,
      intravenous antimicrobials, imaging, blood products, and radiotherapy. Two-thirds
      of patients survived hospitalization and were discharged alive. Survival at 30
      days and 90 days after DNR orders were implemented was 63% and 33%, respectively.
      Baseline Charlson Comorbidity Index score of 5 or less and Eastern Cooperative
      Oncology Group performance status of 2 or less were associated with a higher
      probability of being discharged alive and longer overall survival. CONCLUSIONS:
      Most medical interventions were continued with high frequency in adult oncology
      inpatients after placement of DNR orders. A majority of patients survived
      hospitalization and remained alive at 30 days after DNR orders were documented.
      This study offers some reassurance that DNR orders do not inevitably lead to
      cessation of appropriate medical treatment.

PMID- 24865308
TI  - Detection of extracolonic pathologic findings with CT colonography: a discrete
      choice experiment of perceived benefits versus harms.
AB  - PURPOSE: To determine the maximum rate of false-positive diagnoses that patients
      and health care professionals were willing to accept in exchange for detection of
      extracolonic malignancy by using computed tomographic (CT) colonography for
      colorectal cancer screening. MATERIALS AND METHODS: After obtaining ethical
      approval and informed consent, 52 patients and 50 health care professionals
      undertook two discrete choice experiments where they chose between unrestricted
      CT colonography that examined intra- and extracolonic organs or CT colonography
      restricted to the colon, across different scenarios. The first experiment
      detected one extracolonic malignancy per 600 cases with a false-positive rate
      varying across scenarios from 0% to 99.8%. One experiment examined radiologic
      follow-up generated by false-positive diagnoses while the other examined invasive
      follow-up. Intracolonic performance was identical for both tests. The median
      tipping point (maximum acceptable false-positive rate for extracolonic findings)
      was calculated overall and for both groups by bootstrap analysis. RESULTS: The
      median tipping point for radiologic follow-up occurred at a false-positive rate
      greater than 99.8% (interquartile ratio [IQR], 10 to >99.8%). Participants would
      tolerate at least a 99.8% rate of unnecessary radiologic tests to detect an
      additional extracolonic malignancy. The median tipping-point for invasive follow
      up occurred at a false-positive rate of 10% (IQR, 2 to >99.8%). Tipping points
      were significantly higher for patients than for health care professionals for
      both experiments (>99.8 vs 40% for radiologic follow-up and >99.8 vs 5% for
      invasive follow-up, both P < .001). CONCLUSION: Patients and health care
      professionals are willing to tolerate high rates of false-positive diagnoses with
      CT colonography in exchange for diagnosis of extracolonic malignancy. The actual
      specificity of screening CT colonography for extracolonic findings in clinical
      practice is likely to be highly acceptable to both patients and health care
      professionals. Online supplemental material is available for this article.

PMID- 24865309
TI  - Incidental imaging findings from routine chest CT used to identify subjects at
      high risk of future cardiovascular events.
AB  - PURPOSE: To investigate the contribution of incidental findings at chest computed
      tomography (CT) in the detection of subjects at high risk for cardiovascular
      disease (CVD) by deriving and validating a CT-based prediction rule. MATERIALS
      AND METHODS: This retrospective study was approved by the ethical review board of
      the primary participating facility, and informed consent was waived. The
      derivation cohort comprised 10 410 patients who underwent diagnostic chest CT for
      noncardiovascular indications. During a mean follow-up of 3.7 years (maximum, 7.0
      years), 1148 CVD events (cases) were identified. By using a case-cohort approach,
      CT scans from the cases and from an approximately 10% random sample of the
      baseline cohort (n = 1366) were graded visually for several cardiovascular
      findings. Multivariable Cox proportional hazards analysis with backward
      elimination technique was used to derive the best-fitting parsimonious prediction
      model. External validation (discrimination, calibration, and risk stratification)
      was performed in a separate validation cohort (n = 1653). RESULTS: The final
      model included patient age and sex, CT indication, left anterior descending
      coronary artery calcifications, mitral valve calcifications, descending aorta
      calcifications, and cardiac diameter. The model demonstrated good discriminative
      value, with a C statistic of 0.71 (95% confidence interval: 0.68, 0.74) and a
      good overall calibration, as assessed in the validation cohort. This imaging
      based model allows accurate stratification of individuals into clinically
      relevant risk categories. CONCLUSION: Structured reporting of incidental CT
      findings can mediate accurate stratification of individuals into clinically
      relevant risk categories and subsequently allow those at higher risk of future
      CVD events to be distinguished.

PMID- 24865310
TI  - The Alzheimer structural connectome: changes in cortical network topology with
      increased amyloid plaque burden.
AB  - PURPOSE: To evaluate differences in the structural connectome among patients with
      normal cognition (NC), mild cognitive impairment (MCI), and Alzheimer disease
      (AD) and to determine associations between the structural connectome and cortical
      amyloid deposition. MATERIALS AND METHODS: Patients enrolled in a multicenter
      biomarker study (Alzheimer's Disease Neuroimaging Initiative [ADNI] 2) who had
      both baseline diffusion-tensor (DT) and florbetapir positron emission tomography
      (PET) data at the time of data analyses in November 2012 were studied. All
      institutions received institutional review board approval. There were 102
      patients in ADNI 2 who met criteria for analysis. Patients' T1-weighted images
      were automatically parcellated into cortical regions of interest. Standardized
      uptake value ratio (SUVr) was calculated from florbetapir PET images for
      composite cortical regions (frontal, cingulate, parietal, and temporal).
      Structural connectome graphs were created from DT images, and connectome topology
      was analyzed in each region by using graph theoretical metrics. Analysis of
      variance of structural connectome metrics and florbetapir SUVr across diagnostic
      group was performed. Linear mixed-effects models were fit to analyze the effect
      of florbetapir SUVr on structural connectome metrics. RESULTS: Diagnostic group
      (NC, MCI, or AD) was associated with changes in weighted structural connectome
      metrics, with decreases from the NC group to the MCI group to the AD group shown
      for (a) strength in the bilateral frontal, right parietal, and bilateral temporal
      regions (P < .05); (b) weighted local efficiency in the left temporal region (P <
      .05); and (c) weighted clustering coefficient in the bilateral frontal and left
      temporal regions (P < .05). Increased cortical florbetapir SUVr was associated
      with decreases in weighted structural connectome metrics; namely, strength (P =
      .00001), weighted local efficiency (P = .00001), and weighted clustering
      coefficient (P = .0006), independent of brain region. For every 0.1-unit increase
      in florbetapir SUVr, there was a 14% decrease in strength, an 11% decrease in
      weighted local efficiency, and a 9% decrease in weighted clustering coefficient,
      regardless of the analyzed cortical region or, in the case of weighted local
      efficiency and clustering coefficient, diagnostic group. CONCLUSION: Increased
      amyloid burden, as measured with florbetapir PET imaging, is related to changes
      in the topology of the large-scale cortical network architecture of the brain, as
      measured with graph theoretical metrics of DTI tractography, even in the
      preclinical stages of AD. Online supplemental material is available for this
      article.

PMID- 24865311
TI  - Repeatability of metabolically active tumor volume measurements with FDG PET/CT
      in advanced gastrointestinal malignancies: a multicenter study.
AB  - PURPOSE: To evaluate the feasibility and repeatability of various metabolically
      active tumor volume ( MATV metabolically active tumor volume ) quantification
      methods in fluorine 18 fluorodeoxyglucose ( FDG fluorine 18 fluorodeoxyglucose )
      positron emission tomography (PET)/computed tomography (CT) in a multicenter
      setting and propose the optimal MATV metabolically active tumor volume method
      together with the minimal threshold for future response evaluation studies.
      MATERIALS AND METHODS: The study was approved by the institutional review board
      of all four participating centers, and patients provided written informed
      consent. Thirty-four patients with advanced gastrointestinal malignancies
      underwent two FDG fluorine 18 fluorodeoxyglucose PET/CT examinations within 1
      week. MATV metabolically active tumor volume s were defined semiautomatically
      with 27 variations of tumor delineation methods with different reference values.
      Feasibility was determined as the percentage of successful tumor segmentations
      per MATV metabolically active tumor volume method. Repeatability was determined
      with intraclass correlation coefficients, Bland-Altman plots, and limits of
      agreement ( LOA limit of agreement s) of the percentage difference between the
      test and repeat test measurements. In addition, LOA limit of agreement
      variability per center was investigated. RESULTS: In total, 136 lesions were
      identified. Feasibility of tumor segmentation ranged from 54% to 100% (74-136 of
      136 lesions); repeatability was evaluated for 19 MATV metabolically active tumor
      volume methods with feasibility of greater than 95%. The median MATV
      metabolically active tumor volume derived with 50% threshold of mean standardized
      uptake value ( SUV standardized uptake value ) of a sphere of 12-mm diameter with
      highest local intensity ( SUVhp mean SUV of a sphere of 12-mm diameter with
      highest local intensity ), which may not include the voxel with highest SUV
      standardized uptake value corrected for local background, was 5.7 and 6.1 mL for
      test and retest scans, respectively, with a relative LOA limit of agreement of
      36.1%. Comparable repeatability was found between centers. A difference in uptake
      time between scan 1 and 2 of 15 minutes or longer had a minor negative influence
      on repeatability. CONCLUSION: MATV metabolically active tumor volume measured
      with 50% of SUVhp mean SUV of a sphere of 12-mm diameter with highest local
      intensity corrected for local background is recommended in multicenter FDG
      fluorine 18 fluorodeoxyglucose PET/CT studies on the basis of a high feasibility
      (96%) and repeatability ( LOA limit of agreement of 36.1%).

PMID- 24865313
TI  - Fluorous affinity-based separation techniques for the analysis of biogenic and
      related molecules.
AB  - Perfluoroalkyl-containing compounds have a unique 'fluorous' property that refers
      to the remarkably specific affinity they share. Fluorous compounds can be easily
      isolated from non-fluorous species on the perfluoroalkyl-functionalized
      stationary phases used in fluorous solid-phase extraction and fluorous liquid
      chromatography by means of fluorous-fluorous interactions (fluorophilicity).
      Recently, this unique specificity has been applied to the highly selective
      enrichment and analysis of different classes of biogenic and related compounds in
      complex samples. Because the biogenic compounds are generally not 'fluorous',
      they must be derivatized with appropriate perfluoroalkyl group-containing reagent
      in order to utilize fluorous interaction. In this review, we introduce the
      application of fluorous affinity techniques including derivatization methods to
      biogenic sample analysis. 

PMID- 24865312
TI  - Myocardial CT perfusion imaging and SPECT for the diagnosis of coronary artery
      disease: a head-to-head comparison from the CORE320 multicenter diagnostic
      performance study.
AB  - PURPOSE: To compare the diagnostic performance of myocardial computed tomographic
      (CT) perfusion imaging and single photon emission computed tomography (SPECT)
      perfusion imaging in the diagnosis of anatomically significant coronary artery
      disease (CAD) as depicted at invasive coronary angiography. MATERIALS AND
      METHODS: This study was approved by the institutional review board. Written
      informed consent was obtained from all patients. Sixteen centers enrolled 381
      patients from November 2009 to July 2011. Patients underwent rest and adenosine
      stress CT perfusion imaging and rest and either exercise or pharmacologic stress
      SPECT before and within 60 days of coronary angiography. Images from CT perfusion
      imaging, SPECT, and coronary angiography were interpreted at blinded, independent
      core laboratories. The primary diagnostic parameter was the area under the
      receiver operating characteristic curve (Az). Sensitivity and specificity were
      calculated with use of prespecified cutoffs. The reference standard was a
      stenosis of at least 50% at coronary angiography as determined with quantitative
      methods. RESULTS: CAD was diagnosed in 229 of the 381 patients (60%). The per
      patient sensitivity and specificity for the diagnosis of CAD (stenosis >=50%)
      were 88% (202 of 229 patients) and 55% (83 of 152 patients), respectively, for CT
      perfusion imaging and 62% (143 of 229 patients) and 67% (102 of 152 patients) for
      SPECT, with Az values of 0.78 (95% confidence interval: 0.74, 0.82) and 0.69 (95%
      confidence interval: 0.64, 0.74) (P = .001). The sensitivity of CT perfusion
      imaging for single- and multivessel CAD was higher than that of SPECT, with
      sensitivities for left main, three-vessel, two-vessel, and one-vessel disease of
      92%, 92%, 89%, and 83%, respectively, for CT perfusion imaging and 75%, 79%, 68%,
      and 41%, respectively, for SPECT. CONCLUSION: The overall performance of
      myocardial CT perfusion imaging in the diagnosis of anatomic CAD (stenosis
      >=50%), as demonstrated with the Az, was higher than that of SPECT and was driven
      in part by the higher sensitivity for left main and multivessel disease.

PMID- 24865314
TI  - Percutaneous sclerotherapy of foot venous malformations: evaluation of clinical
      response.
AB  - AIM: To evaluate a single institutional experience with percutaneous
      sclerotherapy of venous malformations (VM) of the foot. MATERIALS AND METHODS:
      Sixteen patients (mean age 14.6 years; range 6-27.3 years), who underwent 34
      sclerotherapy procedures were retrospectively analysed. Technical success, Puig
      classification, VM size reduction, and the complication rate were evaluated. In
      procedures in which C-arm computed tomography (CT) was performed, the VM-to-skin
      surface distance was measured. Additionally, an e-mail-based questionnaire to
      evaluate the response to sclerotherapy was answered by the patients. RESULTS:
      Technical success was 97%. The mean number of procedures per patient was 2.1
      (range 1-5). In all procedures, sodium tetradecyl sulphate foam was used.
      Appropriate follow-up was available for 29/33 procedures (88%). Post-procedural
      complications occurred after 6/29 procedures (21%), all of which were self
      limited skin complications. C-arm CT was performed in 19/33 procedures (58%). The
      lesion-to-skin surface distance was significantly shorter in patients with skin
      post-procedural complications (p < 0.001). The e-mail-based questionnaire was
      completed by 13/16 patients (81%). Decrease in swelling, improvement of foot
      function and a significant decrease in pain (p = 0.003) was reported. No patient
      reported dis-improvement after sclerotherapy. CONCLUSION: Percutaneous
      sclerotherapy is an effective option for treating foot VMs. Skin complication
      rates are higher with shorter VM-to-skin surface distance.

PMID- 24865297
TI  - Klebsormidium flaccidum genome reveals primary factors for plant terrestrial
      adaptation.
AB  - The colonization of land by plants was a key event in the evolution of life. Here
      we report the draft genome sequence of the filamentous terrestrial alga
      Klebsormidium flaccidum (Division Charophyta, Order Klebsormidiales) to elucidate
      the early transition step from aquatic algae to land plants. Comparison of the
      genome sequence with that of other algae and land plants demonstrate that K.
      flaccidum acquired many genes specific to land plants. We demonstrate that K.
      flaccidum indeed produces several plant hormones and homologues of some of the
      signalling intermediates required for hormone actions in higher plants. The K.
      flaccidum genome also encodes a primitive system to protect against the harmful
      effects of high-intensity light. The presence of these plant-related systems in
      K. flaccidum suggests that, during evolution, this alga acquired the fundamental
      machinery required for adaptation to terrestrial environments. 

PMID- 24865316
TI  - Classification of LC chiral stationary phases: Wainer Types I-V revisited.
AB  - The method of classifying LC chiral stationary phases (CSPs) introduced by Irving
      Wainer in 1987 became widely adopted largely because it was based on the
      mechanisms by which the different CSP Types (I-V) achieved chiral recognition and
      was an integral part of a 'how to do chiral LC' package. The classification
      became less used perhaps because it was thought that it was not clear to which
      Type some of the newer CSPs should be assigned. Its only modern day significance
      seemed to be in single enantiomer drug patent litigation cases in defining the
      'state-of-the-art' of chiral LC in the late 1980s. However, on closer inspection,
      it is clear that even with the introduction of many new commercially available
      CSPs, the Wainer classification, perhaps with minor modifications, remains a
      useful suitable vehicle for distinguishing between different groups (Types) of
      CSPs as an aid to chiral LC method development. 

PMID- 24865315
TI  - The appearance of dextranomer-hyaluronic acid copolymer implants on ultrasound
      may predict resolution of vesicoureteral reflux after injection therapy.
AB  - AIM: To investigate the correlation between implant appearance on ultrasound (US)
      and voiding cystourethrography (VCUG) results after dextranomer-hyaluronic acid
      copolymer (DxHA) injection in children with vesicoureteral reflux (VUR).
      MATERIALS AND METHODS: Consecutive cases of primary VUR treated by endoscopic
      subureteral injection of DxHA were retrospectively reviewed. All children had
      postoperative bladder US and VCUG with a mean interval of 34 days and 47 days
      after injection, respectively. VUR resolution at postoperative VCUG was
      considered as treatment success. Implant appearance on US was graded according to
      the retained volume and its location by visual inspection; it was then correlated
      with VCUG results using the Spearman correlation coefficient. RESULTS: A total of
      36 children (56 ureters) were identified in which 38 ureters (68%) had a clearly
      visualized implant on postoperative US and 40 ureters (71%) showed VUR
      resolution. The sensitivity of implant visualization on US for predicting reflux
      resolution was 73% (29/40), specificity 44% (7/16), positive predictive value 76%
      (29/38), and negative predictive value 39% (7/18). The grade 1, grade 2, and
      grade 3 implant appearances showed VUR resolution in 88% (22/25), 54% (7/13), and
      61% (11/18), and showed persistent VUR in 8% (2/25), 15% (2/13), and 28% (5/18),
      respectively (p = 0.032). CONCLUSION: The implant appearance on postoperative US
      showed good correlation with VCUG results in the early post-injection period.
      Large retained implants were associated with treatment success, while small or
      non-visualized implants were related to the persistent reflux.

PMID- 24865317
TI  - Diet carotenoid lutein modulates the expression of genes related to oxygen
      transporters and decreases DNA damage and oxidative stress in mice.
AB  - Lutein (LT) is a carotenoid obtained by diet and despite its antioxidant activity
      had been biochemically reported, few studies are available concerning its
      influence on the expression of antioxidant genes. The expression of 84 genes
      implicated in antioxidant defense was quantified using quantitative reverse
      transcription polymerase chain reaction array. DNA damage was measured by comet
      assay and glutathione (GSH) and thiobarbituric acid reactive substances (TBARS)
      were quantified as biochemical parameters of oxidative stress in mouse kidney and
      liver. cDDP treatment reduced concentration of GSH and increased TBARS,
      parameters that were ameliorated in treatment associated with LT. cDDP altered
      the expression of 32 genes, increasing the expression of GPx2, APC, Nqo1 and CCs.
      LT changed the expression of 37 genes with an induction of 13 mainly oxygen
      transporters. In treatments associating cDDP and LT, 30 genes had their
      expression changed with a increase of the same genes of the cDDP treatment alone.
      These results suggest that LT might act scavenging reactive species and also
      inducing the expression of genes related to a better antioxidant response,
      highlighting the improvement of oxygen transport. This improved redox state of
      the cell through LT treatment could be related to the antigenotoxic and
      antioxidant effects observed. 

PMID- 24865319
TI  - Anaerobic co-digestion of dairy cattle manure and pear waste.
AB  - Anaerobic co-digestion of pre-treated dairy cattle manure (LCM) with pear waste
      after a storage period (PLF) was tested at four inclusion levels: 0%, 25%, 75%
      and 100%. Inclusion levels consisted in the replacement of the volatile solids
      (VS) from the LCM with the VS from PLF keeping the organic loading rate around
      1.1 +/- 0.4 g SVL(-1)d(-1). The introduction of the co-substrate clearly enhanced
      methane production rate (MPR) in comparison to single substrate (phase I) as
      phases II and III, respectively, achieving values 1.3 and 2.8 times higher than
      phase I. The overall performance was optimized for the mixture 25:75 (LCM:PLF;
      v:v). Moreover, storage of pear waste did not compromise its use in AD. This fact
      is important once it can improve waste management from pear production through
      its valorisation as co-substrate in AD process.

PMID- 24865320
TI  - Aurora borealis wraps Plk1 and CDK together.

PMID- 24865321
TI  - Risk factors associated with high prevalence rates of hepatitis C infection in
      Egypt.
AB  - INTRODUCTION: Egypt has the highest reported prevalence of hepatitis C virus
      (HCV) globally. Until now, no systematic review has been conducted to understand
      risk factors associated with these high prevalence rates of HCV. This study
      attempted to identify the various HCV risk factors in Egypt responsible for the
      high incidence and prevalence rates. METHODS: Using systematic literature review
      methods, we searched databases for eligible manuscripts, selecting cohort and
      case-control studies published in English. Peer-reviewed papers published between
      2008 and February 2013 were included. A total of 11 articles met the study
      selection criteria. RESULTS: The most examined risk factors found during our
      review analysis were surgery, transfusion, and age (64-82% of total articles; n =
      11). Multiple risk factors held significant association with HCV infection in the
      included research. CONCLUSIONS: Based on this review, the main HCV risk factor
      categories are unsafe medical practices and familial risk factors. Improving
      medical safety and encouraging familial education on HCV may help reduce the
      incidence of the disease. Most risk factors for HCV transmission in Egypt are
      healthcare-associated. Primary prevention of HCV infection remains important to
      reduce HCV transmission. Further research should also focus on risk factor
      dynamics of HCV in Egypt to reduce transmission and HCV disease burden.

PMID- 24865322
TI  - Prevalence of human T-lymphotropic virus type 1 infection among blood donors in
      mainland China: a meta-analysis.
AB  - BACKGROUND: Human T-lymphotropic virus type 1 (HTLV-1) is considered to be the
      etiological agent of adult T-cell leukemia/lymphoma (ATL) and HTLV-associated
      myelopathy/tropical spastic paraparesis (HAM/TSP). Blood transfusion is a common
      transmission pathway for HTLV-1. However, no surveys to determine the overall
      prevalence of HTLV-1 infection and HTLV-1 genotypes among blood donors on the
      Chinese mainland have yet been conducted. METHODS: A systematic review and meta
      analysis of the peer-reviewed literature on this topic was carried out. Data
      manipulation and statistical analyses were performed using the Comprehensive Meta
      Analysis Version 2.0 program. RESULTS: Forty-four eligible articles involving
      458525 blood donors were selected. Analysis revealed the pooled prevalences of
      HTLV-1 infection among blood donors in Fujian and Guangdong provinces to be
      9.9/10000 (95% confidence interval (CI) 4.4/10000-22.2/10000) and 2.9/10000 (95%
      CI 1.7/10000-4.8/10000), respectively; there were only two cases of HTLV-1
      infection among 204763 donors in other areas of the Chinese mainland. In
      addition, 40 of 42 (95.2%) HTLV-1 isolates belonged to the Transcontinental
      subgroup A of the HTLV-1 subtype A (Cosmopolitan subtype). CONCLUSIONS: The
      prevalence of HTLV-1 infection among blood donors is low and restricted mainly to
      the provinces of Fujian and Guangdong. Most isolates belong to the
      Transcontinental subgroup within HTLV-1 subtype A.

PMID- 24865323
TI  - A novel alternate feeding mode for semi-continuous anaerobic co-digestion of food
      waste with chicken manure.
AB  - A novel alternate feeding mode was introduced to study the possibilities of
      improving methane yield from anaerobic co-digestion of food waste (FW) with
      chicken manure (CM). Two kinds of feeding sequence (a day FW and next day CM
      (FM/CM), two days FM and the third day CM (FW/FM/CM)) were investigated in semi
      continuous anaerobic digestion and lasted 225 days, and the mono-digestions of FW
      and CM were used as control group, respectively. The feeding sequence of FW/CM
      and mono-digestion of CM were observed to fail to produce gas at hydraulic
      retention time (HRT) of 70 days due to the ammonia inhibition, however, the mode
      of FW/FM/CM was proved to successfully run at HRT of 35 days with a higher OLR of
      2.50 kg L(-1)d(-1) and obtain a higher methane production rate of 507.58 ml g(-1)
      VS and volumetric biogas production rate of 2.1 L L(-1)d(-1).

PMID- 24865324
TI  - Modeling the fate of particulate components in aerobic sludge stabilization-
      performance limitations.
AB  - The study investigated the effect of sludge composition on the limitations of
      aerobic stabilization. It was designed with the foresight that the stabilization
      mechanism could only be elucidated if the observed volatile suspended solids
      reduction were correlated with the fate of particulate components in sludge.
      Biomass sustained at sludge ages of 2 and 10 days were used in the stabilization
      reactors. Particulate components were determined by model evaluation of
      corresponding oxygen uptake rate profiles. Interpretation of the experimental
      data by modeling, based on death-regeneration mechanism without external
      substrate, could simulate the fate and evolution of major components in sludge
      during stabilization. It showed that both microbial decay and hydrolysis of non
      viable cellular material proceeded at much slower rates as compared with
      biological systems sustained with substrate feeding. Modeling also indicated that
      particulate metabolic products generated by sludge acclimated to high sludge age
      undergo slow biodegradation under prolonged stabilization.

PMID- 24865325
TI  - CO2 biofixation and carbonic anhydrase activity in Scenedesmus obliquus SA1
      cultivated in large scale open system.
AB  - The present study deals with the large scale open system cultivation of the novel
      microalga: Scenedesmus obliquus SA1 (KC733762) previously isolated in our
      laboratory. SA1 strain was cultivated in open system at varying CO2 levels
      ranging from 0.03% to 35% (v/v) and subsequently the carbonic anhydrase activity
      (CA) and the biochemical properties were monitored. Maximum biomass concentration
      (1.39 +/- 0.023 g L(-1)), CO2 fixation rate (97.65 +/- 1.03 mg L(-1)d(-1)) and
      total CA activity (166.86 +/- 3.30 E.U./mg chla) were obtained at 35% CO2. CA
      inhibitors: acetazolamide and ethoxyzolamide inhibited the external and internal
      enzyme activity in SA1. High CO2 levels were favorable for the accumulation of
      lipids and chlorophyll. The present results suggested that SA1 possessed high CO2
      tolerance and high carbohydrate, lipid and chlorophyll content when cultivated in
      open system thus being suitable for CO2 mitigation in outdoor ponds and
      subsequent generation of value added products.

PMID- 24865326
TI  - Impact of organic loading rate on biohydrogen production in an up-flow anaerobic
      packed bed reactor (UAnPBR).
AB  - This study assesses the impact of organic loading rate on biohydrogen production
      from glucose in an up-flow anaerobic packed bed reactor (UAnPBR). Two mesophilic
      UAPBRs (UAnPBR1 and 2) were tested at organic loading rates (OLRs) ranging from
      6.5 to 51.4 g COD L(-1)d(-1). To overcome biomass washout, design modifications
      were made in the UAnPBR2 to include a settling zone to capture the detached
      biomass. The design modifications in UAnPBR2 increased the average hydrogen yield
      from 0.98 to 2.0 mol-H2 mol(-1)-glucose at an OLR of 25.7 g COD L(-1)d(-1).
      Although, a maximum hydrogen production rate of 23.4 +/- 0.9 L H2 L(-1)d(-1) was
      achieved in the UAnPBR2 at an OLR of 51.4 g COD L(-1)d(-1), the hydrogen yield
      dropped by 50% to around 1 mol-H2 mol(-1)-glucose. The microbiological analysis
      (PCR/DGGE) showed that the biohydrogen production was due to the presence of the
      hydrogen and volatile acid producers such as Clostridium beijerinckii,
      Clostridium butyricum, Megasphaera elsdenii and Propionispira arboris.

PMID- 24865327
TI  - Lignin removal enhancement from prehydrolysis liquor of kraft-based dissolving
      pulp production by laccase-induced polymerization.
AB  - Lignin removal is essential for value-added utilization of hemicelluloses and
      acetic acid present in the prehydrolysis liquor (PHL) of a kraft-based hardwood
      dissolving pulp production. In this paper, a novel process concept, consisting of
      laccase-induced lignin polymerization, followed by filtration/flocculation, was
      developed to enhance the lignin removal. The results showed that the lignin
      removal increased from 11% to 46-61% at laccase concentration of 1-4 U mL(-1).
      The GPC results showed that the molecular weight of the lignin from the laccase
      treated PHL was increased by 160% in comparison with the original one. The
      subsequent flocculation using singular Poly-DADMAC system or dual polymer system
      of Poly-DADMAC/CPAM can further remove 10-15% lignin. The concentrations of
      hemicelluloses and acetic acid were negligibly affected during the laccase
      treatment, while flocculation caused 12-15% of total sugar loss. Additionally,
      the process incorporates this new concept into the kraft-based dissolving pulp
      production process was proposed.

PMID- 24865328
TI  - Pisiform bursitis: a forgotten pathology.
AB  - Pisiform bursitis is a disease often forgotten in both everyday practice and
      medical literature. The pisiform bursa is not constant; when present, it is
      located between the tendon of the flexor carpi ulnaris and pisiform bone.
      Bursitis causes pain in the medial side of the wrist and enters into the
      differential diagnosis of various diseases of this anatomic region, in
      particular, with enthesitis of the flexor carpi ulnaris and the ganglion of piso
      pyramidal compartment. We present the sonographic appearance of pisiform bursitis
      in a symptomatic patient.

PMID- 24865330
TI  - Evaluation of impairment of DNA in marine gastropod, Morula granulata as a
      biomarker of marine pollution.
AB  - The impairment of DNA in marine gastropod Morula granulata was evaluated in terms
      of the loss of DNA integrity in the species as a measure of the impact of
      genotoxic contaminants prevalent in the marine environment along the coast of
      Goa, India. The extent of DNA damage occurred in the marine gastropods collected
      from different sampling sites such as Arambol, Anjuna, Sinquerim, Dona Paula,
      Bogmalo, Hollant, Velsao, Betul and Palolem along the coast of Goa was measured
      following the technique of partial alkaline unwinding as well as comet assays.
      The highest DNA integrity was observed at Arambol (F, 0.75), identified as the
      reference site, whereas the lowest DNA integrity at Hollant (F, 0.33) situated
      between the two most contaminated sites at Bogmalo and Velsao. The impact of
      genotoxic contaminants on marine gastropods was pronounced by their low DNA
      integrity at Sinquerim (F, 0.40) followed by Betul (F, 0.47), Velsao (F, 0.51),
      Anjuna (F, 0.54), Bogmalo (F, 0.55), Dona Paula (F, 0.67) and Palolem (F, 0.70).
      The extent of DNA damage occurred in M. granulata due to ecotoxicological impact
      of the prevailing marine pollutants along the coast of Goa was further
      substantiated by comet assay and expressed in terms of %head-DNA, %tail DNA, tail
      length and Olive tail moment. The single cell gel electrophoresis of M. granulata
      clearly showed relatively higher olive tail moment in the marine gastropod from
      the contaminated sites, Anjuna, Hollant, Velsao and Betul. The variation in the
      mean %head DNA at different sampling sites clearly indicated that the extent of
      DNA damage in marine gastropod increases with the increase in the levels of
      contamination at different sampling sites along the coast. The stepwise multiple
      regression analysis of the water quality parameters showed significant
      correlation between the variation in DNA integrity and PAH in combination with
      NO3, salinity and PO4 (R-(2), 0.90). The measurement of DNA integrity in M.
      granulata thus provides an early warning signal of contamination of the coastal
      ecosystem of Goa by genotoxic contaminants. 

PMID- 24865332
TI  - Plant mineral concentrations related to foraging preferences of western lowland
      gorilla in Central African forest clearings.
AB  - In the Central African rain forest, mineral resources essential to organisms are
      distributed heterogeneously. Forest clearings, locally known as bais, attract
      numerous species presumably due to the mineral richness of these sites, though
      understanding of the factors drawing species to bais remains speculative. Western
      lowland gorillas (Gorilla g. gorilla) selectively feed on particular plant
      species and parts within bais, but studies of such feeding preferences have
      focused on one site. Here, we compared concentrations of minerals and
      macronutrients from plants gorillas consumed and those they did not in 16 bais to
      gain inference regarding drivers of resource selection within bais and bai use.
      The availability of gorilla feeding plants varied between surveyed bais, with
      some consumed species occurring only at a few bais. Regardless of bai specific
      species composition, significantly higher concentrations of Na, K, and Ca were
      found in consumed plants, and other trace minerals were more common in consumed
      plants. In contrast, macronutrients appeared to play no major role in feeding
      plant selectivity with consumed species often having lower concentrations than
      non-consumed species. We found evidence for seasonal differences in Mg and Na
      concentrations, but the concentrations of other minerals in consumed plants were
      consistent across time. These findings provide insight to the drivers of bai
      visitation by gorillas. The high variation in species across bais may elicit use
      of multiple bais, but the general increased mineral composition of consumed
      species across bais suggests metabolic requirements may be met through
      consumption of a variety of species.

PMID- 24865333
TI  - Tracheobronchopathia osteochondroplastica: a review of the literature.
AB  - BACKGROUND: Tracheobronchopathia osteochondroplastica (TBPOCP) is an uncommon
      benign condition affecting the lumen of tracheobronchial tree and characterized
      by abnormal chondrification and ossification. TBPOCP is more frequent than it has
      been reported, as it can be asymptomatic or present with non-specific respiratory
      symptoms. AIMS: In this article, we provide a review of the English literature on
      the condition and discuss its clinical features, general principles, diagnostic
      approaches and current treatment recommendations for TBPOCP. METHODS: We searched
      for all papers indexed in Science Citation Index and Science Citation Index -
      Expanded by using Thomson Reuters Web of Knowledge Web of Science software.
      RESULTS: We reviewed a total of 72 scientific publications. CONCLUSION: In order
      to highlight, diagnosis, treatment and treatment outcomes of TBPOCP, further
      review articles and large case series about this orphan disease are needed.

PMID- 24865334
TI  - Functional analysis and purification of a Pen-2 fusion protein for gamma
      secretase structural studies.
AB  - The 19-transmembrane, multisubunit gamma-secretase complex generates the amyloid
      beta-peptide (Abeta) of Alzheimer's disease (AD) by an unusual intramembrane
      proteolysis of the beta-amyloid precursor protein. The complex, which similarly
      processes many other type 1 transmembrane substrates, is composed of presenilin,
      Aph1, nicastrin, and presenilin enhancer (Pen-2), all of which are necessary for
      proper complex maturation and enzymatic activity. Obtaining a high-resolution
      atomic structure of the intact complex would greatly aid the rational design of
      compounds to modulate activity but is a very difficult task. A complementary
      method is to generate structures for each individual subunit to allow one to
      build a model of the entire complex. Here, we describe a method by which
      recombinant human Pen-2 can be purified from bacteria to > 95% purity at
      milligram quantities per liter, utilizing a maltose binding protein tag to both
      increase solubility and facilitate purification. Expressing the same construct in
      mammalian cells, we show that the large N-terminal maltose binding protein tag on
      Pen-2 still permits incorporation into the complex and subsequent presenilin-1
      endoproteolysis, nicastrin glycosylation and proteolytic activity. These new
      methods provide valuable tools to study the structure and function of Pen-2 and
      the gamma-secretase complex.

PMID- 24865337
TI  - Multimorbidity: what's the problem?

PMID- 24865335
TI  - The mGluR5 negative allosteric modulator dipraglurant reduces dyskinesia in the
      MPTP macaque model.
AB  - BACKGROUND: Blocking metabotropic glutamate receptor type 5 (mGluR5) has been
      proposed as a target for levodopa-induced dyskinesias (LID) in Parkinson's
      disease (PD). We assessed the effect on LID of dipraglurant, a potent selective
      mGluR5 receptor negative allosteric modulator in the gold-standard LID macaque
      model. METHODS: Dipraglurant (3, 10, and 30 mg/kg, by mouth) was tested in the 1
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) macaque model of LID in a four
      way crossover, single-dose, controlled study (n = 8). RESULTS: Dipraglurant
      inhibited dyskinesias in the LID macaque model, with best effect reached at 30
      mg/kg dose with no alteration of levodopa efficacy. CONCLUSION: Acute challenges
      of dipraglurant were efficacious on choreic and dystonic LID in the MPTP-macaque
      model. Dipraglurant pharmacokinetic variables were similar to those of levodopa,
      suggesting that both drugs can be co-administered simultaneously in further
      studies.

PMID- 24865338
TI  - Understanding quality improvement through social network analysis.

PMID- 24865339
TI  - Evidence-based healthcare and quality improvement.
AB  - This is the tenth in a series of articles about the science of quality
      improvement. We explore how evidence-based healthcare relates to quality
      improvement, implementation science and the translation of evidence to improve
      healthcare practice and patient outcomes. Evidence-based practice integrates the
      individual practitioner's experience, patient preferences and the best available
      research information. Incorporating the best available research evidence in
      decision making involves five steps: asking answerable questions, accessing the
      best information, appraising the information for validity and relevance, applying
      the information to care of patients and populations, and evaluating the impact
      for evidence of change and expected outcomes. Major barriers to implementing
      evidence-based practice include the impression among practitioners that their
      professional freedom is being constrained, lack of appropriate training and
      resource constraints. Incentives including financial incentives, guidance and
      regulation are increasingly being used to encourage evidence-based practice. 

PMID- 24865340
TI  - Individual practice and how to improve it.
AB  - Individual practice needs to be developed to improve effectiveness, safety and
      patient experience. Although good systems can support better individual
      performance, without personal development, individual practice can be a source of
      error. This, the final article in our series on the science of quality
      improvement, describes models of competence and practice and the causes of good
      or poor practice. We show how quality improvement techniques can be used to
      improve individual practice and how this can be incorporated into the appraisal
      process for doctors, nurses and other healthcare professionals. 

PMID- 24865341
TI  - Immunisation errors reported to a vaccine advice service: intelligence to improve
      practice.
AB  - BACKGROUND: The success of immunisation programmes depends on the quality with
      which they are administered. The Vaccine Advice for CliniCians Service
      (VACCSline) is an advice service to support immunisers and promote excellence in
      immunisation practice, through specialist guidance and local education, covering
      a catchment population of two million people. All enquiries are recorded onto a
      database and categorised. Vaccine error is selected when a vaccine has not been
      prepared or administered according to national recommendations or relevant expert
      guidance. METHOD: All enquiries from 2009 to 2011, categorised on the VACCSline
      database as 'vaccine error' were analysed and subjected to a detailed free-text
      review. RESULTS: Of 4301 enquiries, 158 (3.7%) concerned vaccine errors. The
      greatest frequency of errors, 145 (92.9%) concerned immunisations delivered in
      primary care services; 92% of all errors occurred during either vaccine selection
      and preparation or history checking and scheduling. Administration of the wrong
      vaccine was the most frequent error recorded in 33.3% of reports. A shared first
      letter of the vaccine name was noted to occur in 13 error reports in which the
      incorrect vaccine was inadvertently administered. Consultations involving pairs
      of siblings were associated with various errors in seven enquiries. Failure to
      revaccinate after spillage (seven reports) showed a widespread knowledge gap in
      this area. CONCLUSION: Advice line enquiries provide intelligence to alert
      immunisers to the errors that are commonly reported and may serve to highlight
      processes that predispose to errors, thus informing immuniser training and
      updating.

PMID- 24865342
TI  - Factors associated with patient satisfaction with primary care in Europe: results
      from the EUprimecare project.
AB  - BACKGROUND: EUprimecare is a study funded by the Seventh Framework Programme of
      the European Union, aimed at analysing the quality of the different models of
      primary care in Europe. The objective of this study was to describe and analyse
      the determinants associated with patient satisfaction in primary care in Europe.
      METHODS: We conducted telephone population surveys among primary care users in
      each EUprimecare consortium country (Germany, Spain, Estonia, Finland, Hungary,
      Italy and Lithuania). The survey was conducted with 3020 patients and the
      questionnaire included sociodemographic variables, health status, and use and
      satisfaction with primary care services. We undertook descriptive analyses,
      bivariate correlations and an ordinal regression model to study the direct
      relationship between levels of satisfaction and the explanatory variables for
      demographics, health status and health services for patients. We present the
      regression coefficients (beta) with 95% confidence intervals and associated tests
      of statistical significance. RESULTS: The mean age of the respondents was 51
      years (SD 14.1). We found significant associations between the level of
      satisfaction and age (beta = 0.008), specialist visits (beta = -0.030), not
      having a general practitioner (beta = 0.70), not measuring weight, cholesterol
      and blood pressure (beta = 0.52), country (beta1 Germany = -1.08 and beta2
      Lithuania = -0.60; beta3 Hungary = 0.50 and beta4 Italy = 0.53) and a better
      perception of health status (beta = 0.33). Specialist visits had a negative
      association with satisfaction. CONCLUSIONS: Overall, the results indicate factors
      that may be related to greater satisfaction with primary care services: age,
      visits to a specialist, having a doctor assigned to primary care and measurement
      of control parameters are associated with a better perception of the care
      received.

PMID- 24865343
TI  - Do local enhanced services in primary care improve outcomes? Results from a
      literature review.
AB  - OBJECTIVE: This paper aims to examine the role of local enhanced services (LES)
      as a financial incentive in improving clinical and process outcomes in primary
      care with a view to discussing their future in light of the Health and Social
      Care Act. METHODS: A literature review was conducted to identify LES commissioned
      in the UK in any disease area and to evaluate common themes relating to their
      impact on outcomes. The literature review consisted of two stages: an initial
      reference database search (MEDLINE, MEDLINE IN-PROCESS and EMBASE) and a more
      general internet search. The internet search used free text augmented by a
      targeted search of key health organisations' websites. Data were extracted from
      the LES to provide information on the background and context of the LES before
      going on to describe the incentive structure, health and economic outcomes and
      limitations of the LES. RESULTS: Although a number of LES were identified in the
      online search, only 14 reported any data on outcomes. These LES programmes
      related to 10 different disease areas, with cancer, alcohol dependence and
      chronic obstructive pulmonary disease (COPD) being the most common health needs.
      Three common factors between the selected LES emerged that appear to influence
      the extent of the impact on local health or economic outcomes: (1) a national
      framework supporting the LES, (2) existing service provision, and (3) the size of
      the financial incentives. CONCLUSION: The common themes emerging from the
      literature review suggest that, following the Health and Social Care Act 2012 and
      newly established national standards, given sufficient attention to planning
      service specifications, LES could continue to be important in reducing health
      inequalities and preparing poorly performing general practices for longer term
      changes directed at improving outcomes and standards in healthcare.

PMID- 24865344
TI  - Cytochrome P450-2D6*4 polymorphism seminal relationship in infertile men.
AB  - This study aimed to assess cytochrome (CY) P450-2D6*4 polymorphism relationship
      with semen variables in infertile men. In all, 308 men were included; fertile
      normozoospermia (N) (n = 77), asthenozoospermia (A) (n = 70),
      asthenoteratozoospermia (AT) (n = 75) and oligoasthenoteratozoospermia (OAT) (n =
      86). They were subjected to history taking, clinical examination, semen analysis,
      sperm acrosin activity, seminal malondialdehyde (MDA) and CYP450-2D6*4
      genotyping. CYP450-2D6*4 wild-type allele was represented in 76.5% of N, 70% of
      A, 66.7% of AT and 57.7% of OAT men where homozygous gene mutation was present in
      5.9% of N, 20% of A, 26.6% of AT and 26.9% of OAT men, respectively. Sperm
      acrosin activity, sperm concentration, sperm motility, linear sperm velocity and
      sperm normal forms were significantly higher, and seminal MDA level was
      significantly lower in men with CYP450-2D6*4 wild-type allele compared with men
      with homozygous mutation. It is concluded that CYP450-2D6*4 wild-type allele has
      higher frequency where homozygous-type allele has lower frequency in N men
      compared with A, AT and OAT men. Sperm acrosin activity index, sperm
      concentration, sperm motility, linear sperm velocity and sperm normal forms were
      significantly higher, and seminal MDA level was significantly lower in men with
      CYP450-2D6*4 wild-type allele compared with men with homozygous mutation. 

PMID- 24865345
TI  - Congenital hyperinsulinism: global and Japanese perspectives.
AB  - Over the past 20 years, there has been remarkable progress in the diagnosis and
      treatment of congenital hyperinsulinism (CHI). These advances have been supported
      by the understanding of the molecular mechanism and the development of diagnostic
      modalities to identify the focal form of ATP-sensitive potassium channel CHI.
      Many patients with diazoxide-unresponsive focal CHI have been cured by partial
      pancreatectomy without developing postsurgical diabetes mellitus. Important novel
      findings on the genetic basis of the other forms of CHI have also been obtained,
      and several novel medical treatments have been explored. However, the management
      of patients with CHI is still far from ideal. First, state-of-the-art treatment
      is not widely available worldwide. Second, it appears that the management
      strategy needs to be adjusted according to the patient's ethnic group. Third,
      optimal management of patients with the diazoxide-unresponsive, diffuse form of
      CHI is still insufficient and requires further improvement. In this review, we
      describe the current landscape of this disorder, discuss the racial disparity of
      CHI using Japanese patients as an example, and briefly note unanswered questions
      and unmet needs that should be addressed in the near future. 

PMID- 24865349
TI  - First report of polymelia and a rudimentary wing in a Nigerian Nera black
      chicken.
AB  - A case of polymelia with a rudimentary wing is described in an eight-week-old
      Nera black chicken (Gallus domesticus). It is a rare disorder with chromosomal
      aberrations, which are associated with congenital limb malformations. The
      condition was observed during routine physical examination of a flock of 2000
      poultry birds in the month of February 2008 in Ibadan, Nigeria. After physical
      examination, the bird was found to have two extra well-developed legs, which were
      shorter than the normal legs. These extra legs were also found to be non
      functional. Similarly, a rudimentary wing, which was highly vestigial, was found
      on the left lateral side of the bird very close to the cloaca. The bird died at
      the age of eight weeks. This is the first reported case of polymelia with a
      rudimentary wing in a domestic chicken in Nigeria. 

PMID- 24865347
TI  - CBX7 modulates the expression of genes critical for cancer progression.
AB  - BACKGROUND: We have previously shown that the expression of CBX7 is drastically
      decreased in several human carcinomas and that its expression progressively
      decreases with the appearance of a highly malignant phenotype. The aim of our
      study has been to investigate the mechanism by which the loss of CBX7 expression
      may contribute to the emergence of a more malignant phenotype. METHODS: We
      analyzed the gene expression profile of a thyroid carcinoma cell line after the
      restoration of CBX7 and, then, analyzed the transcriptional regulation of
      identified genes. Finally, we evaluated the expression of CBX7 and regulated
      genes in a panel of thyroid and lung carcinomas. RESULTS: We found that CBX7
      negatively or positively regulates the expression of several genes (such as SPP1,
      SPINK1, STEAP1, and FOS, FOSB, EGR1, respectively) associated to cancer
      progression, by interacting with their promoter regions and modulating their
      transcriptional activity. Quantitative RT-PCR analyses in human thyroid and lung
      carcinoma tissues revealed a negative correlation between CBX7 and its down
      regulated genes, while a positive correlation was observed with up-regulated
      genes. CONCLUSION: In conclusion, the loss of CBX7 expression might play a
      critical role in advanced stages of carcinogenesis by deregulating the expression
      of specific effector genes.

PMID- 24865346
TI  - Pharmacologic inhibition of bone resorption prevents cancer-induced osteolysis
      but enhances soft tissue metastasis in a mouse model of osteolytic breast cancer.
AB  - Osteoprotegerin (OPG) is a secreted member of the TNF receptor superfamily, which
      binds to the receptor activator of nuclear factor kappaB ligand (RANKL) and
      inhibits osteoclast activity and bone resorption. Systemic administration of
      recombinant OPG was previously shown to inhibit tumor growth in bone and to
      prevent cancer-induced osteolysis. In this study, we examined the effect of OPG,
      when produced locally by breast cancer cells located within bone, using a mouse
      model of osteolytic breast cancer. MDA-MB-231-TXSA breast cancer cells, tagged
      with a luciferase reporter gene construct and engineered to overexpress full
      length human OPG, were transplanted directly into the tibial marrow cavity of
      nude mice. Overexpression of OPG by breast cancer cells protected the bone from
      breast cancer-induced osteolysis and diminished intra-osseous tumor growth but
      had no effect on extra-skeletal tumor growth. This effect was associated with a
      significant reduction in the number of osteoclasts that lined the bone surface,
      resulting in a net increase in bone volume. Despite limiting breast cancer
      mediated bone loss, OPG overexpression resulted in a significant increase in the
      incidence of pulmonary metastasis. Our results demonstrate that inhibition of
      osteoclastic bone resorption by OPG when secreted locally by tumors in bone may
      affect the behaviour of cancer cells within the bone microenvironment and their
      likelihood of spreading and establishing metastasis elsewhere in the body. 

PMID- 24865350
TI  - Phylogenetic species identification in Rattus highlights rapid radiation and
      morphological similarity of New Guinean species.
AB  - The genus Rattus is highly speciose, the taxonomy is complex, and individuals are
      often difficult to identify to the species level. Previous studies have
      demonstrated the usefulness of phylogenetic approaches to identification in
      Rattus but some species, especially among the endemics of the New Guinean region,
      showed poor resolution. Possible reasons for this are simple misidentification,
      incomplete gene lineage sorting, hybridization, and phylogenetically distinct
      lineages that are unrecognised taxonomically. To assess these explanations we
      analysed 217 samples, representing nominally 25 Rattus species, collected in New
      Guinea, Asia, Australia and the Pacific. To reduce misidentification problems we
      sequenced museum specimens from earlier morphological studies and recently
      collected tissues from samples with associated voucher specimens. We also
      reassessed vouchers from previously sequenced specimens. We inferred combined and
      separate phylogenies from two mitochondrial DNA regions comprising 550 base pair
      D-loop sequences and both long (655 base pair) and short (150 base pair)
      cytochrome oxidase I sequences. Our phylogenetic species identification for 17
      species was consistent with morphological designations and current taxonomy thus
      reinforcing the usefulness of this approach. We reduced misidentifications and
      consequently the number of polyphyletic species in our phylogenies but the New
      Guinean Rattus clades still exhibited considerable complexity. Only three of our
      eight New Guinean species were monophyletic. We found good evidence for either
      incomplete mitochondrial lineage sorting or hybridization between species within
      two pairs, R. leucopus/R. cf. verecundus and R. steini/R. praetor. Additionally,
      our results showed that R. praetor, R. niobe and R. verecundus each likely
      encompass more than one species. Our study clearly points to the need for a
      revised taxonomy of the rats of New Guinea, based on broader sampling and
      informed by both morphology and phylogenetics. The remaining taxonomic complexity
      highlights the recent and rapid radiation of Rattus in the Australo-Papuan
      region. 

PMID- 24865351
TI  - Gait biomechanics of individuals with transtibial amputation: effect of
      suspension system.
AB  - Prosthetic suspension system is an important component of lower limb prostheses.
      Suspension efficiency can be best evaluated during one of the vital activities of
      daily living, i.e. walking. A new magnetic prosthetic suspension system has been
      developed, but its effects on gait biomechanics have not been studied. This study
      aimed to explore the effect of suspension type on kinetic and kinematic gait
      parameters during level walking with the new suspension system as well as two
      other commonly used systems (the Seal-In and pin/lock). Thirteen persons with
      transtibial amputation participated in this study. A Vicon motion system (six
      cameras, two force platforms) was utilized to obtain gait kinetic and kinematic
      variables, as well as pistoning within the prosthetic socket. The gait deviation
      index was also calculated based on the kinematic data. The findings indicated
      significant difference in the pistoning values among the three suspension
      systems. The Seal-In system resulted in the least pistoning compared with the
      other two systems. Several kinetic and kinematic variables were also affected by
      the suspension type. The ground reaction force data showed that lower load was
      applied to the limb joints with the magnetic suspension system compared with the
      pin/lock suspension. The gait deviation index showed significant deviation from
      the normal with all the systems, but the systems did not differ significantly.
      Main significant effects of the suspension type were seen in the GRF (vertical
      and fore-aft), knee and ankle angles. The new magnetic suspension system showed
      comparable effects in the remaining kinetic and kinematic gait parameters to the
      other studied systems. This study may have implications on the selection of
      suspension systems for transtibial prostheses. Trial registration: Iranian
      Registry of Clinical Trials IRCT2013061813706N1.

PMID- 24865352
TI  - Structuring osteosarcoma knowledge: an osteosarcoma-gene association database
      based on literature mining and manual annotation.
AB  - Osteosarcoma (OS) is the most common primary bone cancer exhibiting high genomic
      instability. This genomic instability affects multiple genes and microRNAs to a
      varying extent depending on patient and tumor subtype. Massive research is
      ongoing to identify genes including their gene products and microRNAs that
      correlate with disease progression and might be used as biomarkers for OS.
      However, the genomic complexity hampers the identification of reliable
      biomarkers. Up to now, clinico-pathological factors are the key determinants to
      guide prognosis and therapeutic treatments. Each day, new studies about OS are
      published and complicate the acquisition of information to support biomarker
      discovery and therapeutic improvements. Thus, it is necessary to provide a
      structured and annotated view on the current OS knowledge that is quick and
      easily accessible to researchers of the field. Therefore, we developed a publicly
      available database and Web interface that serves as resource for OS-associated
      genes and microRNAs. Genes and microRNAs were collected using an automated
      dictionary-based gene recognition procedure followed by manual review and
      annotation by experts of the field. In total, 911 genes and 81 microRNAs related
      to 1331 PubMed abstracts were collected (last update: 29 October 2013). Users can
      evaluate genes and microRNAs according to their potential prognostic and
      therapeutic impact, the experimental procedures, the sample types, the biological
      contexts and microRNA target gene interactions. Additionally, a pathway
      enrichment analysis of the collected genes highlights different aspects of OS
      progression. OS requires pathways commonly deregulated in cancer but also
      features OS-specific alterations like deregulated osteoclast differentiation. To
      our knowledge, this is the first effort of an OS database containing manual
      reviewed and annotated up-to-date OS knowledge. It might be a useful resource
      especially for the bone tumor research community, as specific information about
      genes or microRNAs is quick and easily accessible. Hence, this platform can
      support the ongoing OS research and biomarker discovery. Database URL:
      http://osteosarcoma-db.uni-muenster.de. 

PMID- 24865354
TI  - Why there is no legal or medical justification for the Saatchi bill.

PMID- 24865355
TI  - Growth inhibition effects of isoalantolactone on K562/A02 cells: caspase
      dependent apoptotic pathways, S phase arrest, and downregulation of Bcr/Abl.
AB  - Isoalantolactone, a sesquiterpene lactone, is the active component of Inula
      helenium (Compositae). It has been reported that isoalantolactone has the
      capacity to inhibit tumor cell growth through induction of apoptosis. The
      purposes of this study were to evaluate the effects of isoalantolactone on the
      human erythroleukemia drug-resistant cell line K562/A02 and to provide evidence
      of its function as a potent therapeutic agent in patients with chronic
      myelogenous leukemia with the Bcr/Abl phenotype. Our results showed that
      isoalantolactone significantly inhibited K562/A02 cell growth by downregulating
      Bcr/Abl expression. Isoalantolactone also induced apoptosis via increase
      generation of reactive oxygen species, modulation of the protein levels of Bcl-2
      family members, caspase activation, poly ADP-ribose polymerase (PARP) cleavage,
      and release of cytochrome c. We also observed that isoalantolactone inhibited
      proliferation by inducing cell cycle arrest in the S phase. Taken together, all
      these findings support that growth inhibition effects of isoalantolactone on
      K562/A02 cells may be mediated through caspase-dependent apoptotic pathways, S
      phase arrest, and downregulation of Bcr/Abl.

PMID- 24865357
TI  - Panic disorder and agoraphobia: an overview and commentary on DSM-5 changes.
AB  - The recently published DSM-5 contains a number of changes pertinent to panic
      disorder and agoraphobia. These changes include separation of panic disorder and
      agoraphobia into separate diagnoses, the addition of criteria and guidelines for
      distinguishing agoraphobia from specific phobia, the addition of a 6-month
      duration requirement for agoraphobia, the addition of panic attacks as a
      specifier to any DSM-5 diagnosis, changes to descriptors of panic attack types,
      as well as various changes to the descriptive text. It is crucial that clinicians
      and researchers working with individuals presenting with panic attacks and panic
      like symptoms understand these changes. The purpose of the current paper is to
      provide a summary of the main changes, to critique the changes in the context of
      available empirical evidence, and to highlight clinical implications and
      potential impact on mental health service utilization. Several of the changes
      have the potential to improve access to evidence-based treatment; yet, although
      certain changes appear justified in that they were based on converging evidence
      from different empirical sources, other changes appear questionable, at least
      based on the information presented in the DSM-5 text and related publications.
      Ongoing research of DSM-5 panic disorder and agoraphobia as well as application
      of the new diagnostic criteria in clinical contexts is needed to further inform
      the strengths and limitations of DSM-5 conceptualizations of panic disorder and
      agoraphobia. 

PMID- 24865360
TI  - Efficient visible light photocatalyst fabricated by depositing plasmonic Ag
      nanoparticles on conductive polymer-protected Si nanowire arrays for
      photoelectrochemical hydrogen generation.
AB  - Photoelectrochemical (PEC) water splitting to produce H2 is a renewable method
      for addressing the worldwide energy consumption increasing and fossil fuels
      storage shrinking. In order to achieve sustainable PEC H2 production, the
      semiconductor electrodes should have good photo-absorption ability, proper band
      positions, and chemical stability in aqueous condition. Different from the large
      band-gap semiconductors such as TiO2, which can work efficiently under UV light,
      Si is an narrow-band-gap semiconductor that can efficiently absorb visible light;
      however, Si is indirect semiconductor and susceptible to photocorrosion in
      aqueous solution. In this paper, we demonstrate a new strategy of first
      protecting and then activating to develop a stable visible light photoanode for
      photoelectrochemical hydrogen production. This AgNPs/PEDOT/SiNW arrays show an
      encouraging solar-to-chemical energy conversion efficiency of 2.86 % and a
      pronounced incident photo-to-current conversion efficiency (IPCE) across the
      whole visible region. Our strategy proposed here contributes to further
      improvement of corrosion protection and solar energy harvesting for narrow-band
      gap semiconductors that employed in visible light photoelectrochemical and
      photoelectric conversion applications. 

PMID- 24865362
TI  - Edelfosine lipid nanoparticles overcome multidrug resistance in K-562 leukemia
      cells by a caspase-independent mechanism.
AB  - The antitumor ether lipid edelfosine is the prototype of a novel generation of
      promising anticancer drugs that has been shown to be an effective antitumor agent
      in numerous malignancies. However, several cancer types display resistance to
      different antitumoral compounds due to multidrug resistance (MDR). Thus, MDR is a
      major drawback in anticancer therapy. In that sense, the leukemic cell line K-562
      shows resistance to edelfosine. This resistance is overcome by the use of
      nanotechnology. The present work describes the rate and mechanism of
      internalization of free and nanoencapsulated edelfosine. The molecular mechanisms
      underlying cell death are described in the present paper by characterization of
      several molecules implied in the apoptosic and autophagic pathways (PARP, LC3IIB,
      caspases-3, -9 and -7), and their pattern of expression is compared with the cell
      induction in a sensitive cell line HL-60. Results showed different
      internalization patterns in both cells. Clathrin and lipid raft mediated
      endocytosis were observable in edelfosine uptake, whereas these mechanism were
      not visible in the uptake of lipid nanoparticles, which might suffer phagocytosis
      and macropinocytosis. Both treatments induced caspase-mediated apoptosis in HL-60
      cells, whereas this cell death mechanism was unnoticeable in K-562 cells.
      Moreover, an important increase in autophagic vesicles was visible in K-562
      cells. Thus, this mechanism might be implicated in overcoming K-562 resistance
      with the treatment by lipid nanoparticles. 

PMID- 24865365
TI  - Molecular mechanics of elastic and bendable caffeine co-crystals.
AB  - Complementing recent experimental results, here we report a computational study
      of remarkably flexible, elastically bendable caffeine cocrystals (cocrystal
      solvate 1), formed from caffeine (CAF), 4-chloro-3-nitrobenzoic acid (CNB), and
      methanol, and compare with its unsolvated brittle form, 1 (dry). We show that 1
      is able to maintain stable cocrystal structures at temperatures between 100 K and
      400 K. The tensile and compressive Young's modulus of 1 are close to ~10 GPa. The
      ultimate strength is more than 600 MPa in tensile and 400 MPa in compressive at
      temperature of 100 K. The simulation results of the structural and mechanical
      properties of 1 are in good agreement with our previous experimental work.
      Notably, before the ultimate tensile stress, the stress-to-strain curves of 1
      show linear behavior, but 1 (dry) show nonlinear behavior. This study might
      explain the remarkable elasticity of 1 and is relevant to the design of high
      performance organic materials with excellent self-healing or efficient stress
      dissipating properties.

PMID- 24865369
TI  - Pentafluorophenyl transfer reaction: preparation of pentafluorophenyl
      [60]fullerene adducts through opening of fullerene epoxide moiety with
      trispentafluorophenylborane.
AB  - Unlike the extensively studied perfluoroalkyl fullerene adducts, perfluorophenyl
      fullerene adducts are quite difficult to prepare by known methods.
      Trispentafluorophenylborane was found to react with fullerene epoxide to form the
      1,2-perfluorophenylfullerenol. The method can be applied to both the simple
      epoxide C60(O) and fullerene multiadducts containing an epoxide moiety. Single
      crystal X-ray structure analysis confirmed the addition of the pentafluorophenyl
      group. 

PMID- 24865370
TI  - A metabolomics approach for predicting the response to neoadjuvant chemotherapy
      in cervical cancer patients.
AB  - Cervical cancer is a clinical and pathological heterogeneity disease, which
      requires different types of treatments and leads to a variety of outcomes. In
      clinical practice, only some patients benefit from chemotherapy treatment.
      Identifying patients who will be responsive to chemotherapy could increase their
      survival time, which has important implications in personalized treatment and
      outcomes, while identifying non-responders may reduce the likelihood for these
      patients to receive ineffective treatment and thereby enable them to receive
      other potentially effective treatments. Plasma metabolite profiling was performed
      in this study to identify the potential biomarkers that could predict the
      response to neoadjuvant chemotherapy (NACT) for cervical cancer patients. The
      metabolic profiles of plasma from 38 cervical cancer patients with a complete,
      partial and non-response to NACT were studied using a combination of liquid
      chromatography coupled with mass spectrometry (LC/MS) and multivariate analysis
      methods. L-Valine and L-tryptophan were finally identified and verified as the
      potential biomarkers. A prediction model constructed with L-valine and L
      tryptophan correctly identified approximately 80% of patients who were non
      response to chemotherapy and 87% of patients who were had a pathologically
      complete response to chemotherapy. The model has an excellent discriminant
      performance with an AUC of 0.9407. These results show promise for larger studies
      that could produce more personalized treatment protocols for cervical cancer
      patients.

PMID- 24865371
TI  - Beyond consent in research. Revisiting vulnerability in deep brain stimulation
      for psychiatric disorders.
AB  - Vulnerability is an important criterion to assess the ethical justification of
      the inclusion of participants in research trials. Currently, vulnerability is
      often understood as an attribute inherent to a participant by nature of a
      diagnosed condition. Accordingly, a common ethical concern relates to the
      participant's decisionmaking capacity and ability to provide free and informed
      consent. We propose an expanded view of vulnerability that moves beyond a focus
      on consent and the intrinsic attributes of participants. We offer specific
      suggestions for how relational aspects and the dynamic features of vulnerability
      could be more fully captured in current discussions and research practices.

PMID- 24865372
TI  - Additive surface complexation modeling of uranium(VI) adsorption onto quartz-sand
      dominated sediments.
AB  - Many aquifers contaminated by U(VI)-containing acidic plumes are composed
      predominantly of quartz-sand sediments. The F-Area of the Savannah River Site
      (SRS) in South Carolina (USA) is an example. To predict U(VI) mobility and
      natural attenuation, we conducted U(VI) adsorption experiments using the F-Area
      plume sediments and reference quartz, goethite, and kaolinite. The sediments are
      composed of ~96% quartz-sand and 3-4% fine fractions of kaolinite and goethite.
      We developed a new humic acid adsorption method for determining the relative
      surface area abundances of goethite and kaolinite in the fine fractions. This
      method is expected to be applicable to many other binary mineral pairs, and
      allows successful application of the component additivity (CA) approach based
      surface complexation modeling (SCM) at the SRS F-Area and other similar aquifers.
      Our experimental results indicate that quartz has stronger U(VI) adsorption
      ability per unit surface area than goethite and kaolinite at pH <= 4.0. Our
      modeling results indicate that the binary (goethite/kaolinite) CA-SCM under
      predicts U(VI) adsorption to the quartz-sand dominated sediments at pH <= 4.0.
      The new ternary (quartz/goethite/kaolinite) CA-SCM provides excellent
      predictions. The contributions of quartz-sand, kaolinite, and goethite to U(VI)
      adsorption and the potential influences of dissolved Al, Si, and Fe are also
      discussed. 

PMID- 24865374
TI  - Direct arylation as a versatile tool towards thiazolo[5,4-d]thiazole-based
      semiconducting materials.
AB  - A series of thiazolo[5,4-d]thiazole-based small molecule organic optoelectronic
      materials is synthesized via a straightforward microwave-activated Pd-catalyzed C
      H arylation protocol. The procedure allows us to obtain extended 2,5
      dithienylthiazolo[5,4-d]thiazole chromophores with tailor-made energy levels and
      absorption patterns, depending on the introduced (het)aryl moieties and the
      molecular (a)symmetry, by shortened sequences without organometallic
      intermediates. The synthesized materials can be applied as either electron donor
      or electron acceptor light-harvesting materials in molecular bulk heterojunction
      organic solar cells. 

PMID- 24865373
TI  - Emotional reactivity and emotion regulation among adults with a history of self
      harm: laboratory self-report and functional MRI evidence.
AB  - Intentionally hurting one's body (deliberate self-harm; DSH) is theorized to be
      associated with high negative emotional reactivity and poor emotion regulation
      ability. However, little research has assessed the relationship between these
      potential risk factors and DSH using laboratory measures. Therefore, we conducted
      2 studies using laboratory measures of negative emotional reactivity and emotion
      regulation ability. Study 1 assessed self-reported negative emotions during a sad
      film clip (reactivity) and during a sad film clip for which participants were
      instructed to use reappraisal (regulation). Those with a history of DSH were
      compared with 2 control groups without a history of DSH matched on key
      demographics: 1 healthy group low in depression and anxiety symptoms and 1 group
      matched to the DSH group on depression and anxiety symptoms. Study 2 extended
      Study 1 by assessing neural responding to negative images (reactivity) and
      negative images for which participants were instructed to use reappraisal
      (regulation). Those with a history of DSH were compared with a control group
      matched to the DSH group on demographics, depression, and anxiety symptoms.
      Compared with control groups, participants with a history of DSH did not exhibit
      greater negative emotional reactivity but did exhibit lower ability to regulate
      emotion with reappraisal (greater self-reported negative emotions in Study 1 and
      greater amygdala activation in Study 2 during regulation). These results suggest
      that poor emotion regulation ability, but not necessarily greater negative
      emotional reactivity, is a correlate of and may be a risk factor for DSH, even
      when controlling for mood disorder symptoms.

PMID- 24865375
TI  - Three-dimensional temporal bone reconstruction from histological sections.
AB  - OBJECTIVE: To produce a high-resolution, three-dimensional temporal bone model
      from serial sections, using a personal computer. METHOD: Digital images were
      acquired from histological sections of the temporal bone. Image registration,
      segmentation and three-dimensional volumetric reconstruction were performed using
      a personal computer. The model was assessed for anatomical accuracy and
      interactivity by otologists. RESULTS: An accurate, high-resolution, three
      dimensional model of the temporal bone was produced, containing structures
      relevant to otological surgery. The facial nerve, labyrinth, internal carotid
      artery, jugular bulb and all of the ossicles were seen (including the stapes
      footplate), together with the internal and external auditory meati. Some
      projections also showed the chorda tympani nerve. CONCLUSION: A high-resolution,
      three-dimensional computer model of the complete temporal bone was produced using
      a personal computer. Because of the increasing difficulty in procuring cadaveric
      bones, this model could be a useful adjunct for training.

PMID- 24865380
TI  - Synemin: an evolving role in tumor growth and progression.

PMID- 24865376
TI  - Investigating the impact of Asp181 point mutations on interactions between PTP1B
      and phosphotyrosine substrate.
AB  - Protein tyrosine phosphatase 1B (PTP1B) is a key negative regulator of insulin
      and leptin signaling, which suggests that it is an attractive therapeutic target
      in type II diabetes and obesity. The aim of this research is to explore residues
      which interact with phosphotyrosine substrate can be affected by D181 point
      mutations and lead to increased substrate binding. To achieve this goal,
      molecular dynamics simulations were performed on wild type (WT) and two mutated
      PTP1B/substrate complexes. The cross-correlation and principal component analyses
      show that point mutations can affect the motions of some residues in the active
      site of PTP1B. Moreover, the hydrogen bond and energy decomposition analyses
      indicate that apart from residue 181, point mutations have influence on the
      interactions of substrate with several residues in the active site of PTP1B. 

PMID- 24865379
TI  - Characterization of single spore isolates of Agaricus bisporus (Lange) Imbach
      using conventional and molecular methods.
AB  - Strains A-15, S11, S-140, and U3 of Agaricus bisporus (Lange) Imbach, were used
      as parent strains for raising single spore homokaryotic isolates. Out of total
      1,642 single spore isolates, only 36 single spore isolates were homokaryons and
      exhibited slow mycelial growth rate (<=2.0 mm/day) and appressed colony
      morphology. All these SSIs failed to produce pinheads in Petri plates even after
      65 days of incubation, whereas the strandy slow growing SSIs along with parent
      strains were able to form the fructification in petriplates after 30 days. Out of
      24, six ISSR primers, exhibited scorable bands. In the ISSR fingerprints, single
      spore isolates, homokaryons, lacked amplification products at multiple loci; they
      grow slowly and all of them had appressed types of colony morphology. The study
      revealed losses of ISSR polymorphic patterns in non-fertile homokaryotic single
      spore isolates compared to the parental control or fertile heterokaryotic single
      spore isolates. 

PMID- 24865381
TI  - Are we closer to having drugs to treat muscle wasting disease?
AB  - The two most common muscle wasting diseases in adults are sarcopenia and
      cachexia. Despite differences in their pathophysiology, it is believed that both
      conditions are likely to respond to drugs that increase muscle mass and muscle
      strength. The current gold standard in this regard is exercise training. This
      article provides an overview of candidate drugs to treat muscle wasting disease
      that are available or in development. Drugs highlighted here include ghrelin
      agonists, selective androgen receptor molecules, megestrol acetate, activin
      receptor antagonists, espindolol, and fast skeletal muscle troponin inhibitors. 

PMID- 24865382
TI  - Three-dimensional data interpolation for environmental purpose: lead in
      contaminated soils in southern Brazil.
AB  - Monitoring of heavy metal contamination plume in soils can be helpful in
      establishing strategies to minimize its hazardous impacts to the environment. The
      objective of this study was to apply a new approach of visualization, based on
      tridimensional (3D) images, of pseudo-total (extracted with concentrated acids)
      and exchangeable (extracted with 0.5 mol L(-1) Ca(NO3)2) lead (Pb) concentrations
      in soils of a mining and metallurgy area to determine the spatial distribution of
      this pollutant and to estimate the most contaminated soil volumes. Tridimensional
      images were obtained after interpolation of Pb concentrations of 171 soil samples
      (57 points * 3 depths) with regularized spline with tension in a 3D function
      version. The tridimensional visualization showed great potential of use in
      environmental studies and allowed to determine the spatial 3D distribution of Pb
      contamination plume in the area and to establish relationships with soil
      characteristics, landscape, and pollution sources. The most contaminated soil
      volumes (10,001 to 52,000 mg Pb kg(-1)) occurred near the metallurgy factory. The
      main contamination sources were attributed to atmospheric emissions of
      particulate Pb through chimneys. The large soil volume estimated to be removed to
      industrial landfills or co-processing evidenced the difficulties related to this
      practice as a remediation strategy.

PMID- 24865383
TI  - Nutrient dynamics and seasonal variation of phytoplankton assemblages in the
      coastal waters of southwest Bay of Bengal.
AB  - In order to understand the phytoplankton community structure and its relationship
      with the environmental variables in the near shore waters of Kalpakkam, east
      coast of India, observations were carried out during 2008-2009. Phytoplankton
      population was comprised of 219 species, and the density was higher during the
      southwest monsoon (SWM) and inter-monsoon seasons than that of north east monsoon
      (NEM) season. The nutrient status on a temporal and spatial scale indicated the
      impact of point sources carrying anthropogenic runoff. Comparison of ambient
      nutrient ratios with the Redfield ratio (N/P/Si = 16:1:16) showed a clear
      temporal variation in the factors that regulate the phytoplankton growth. SWM and
      inter-monsoon season was evident to have an acute N-limitation of algal growth
      (~76%) whereas P-limitation was encountered during the NEM season (~75%).
      Interestingly, a sizable population of cyanobacteria (Trichodesmium erythraeum)
      were noticed during NEM season when there was an exponential increase in nitrogen
      concentration, probably due to nitrogen fixation. No significant impact of
      temperature on phytoplankton proliferation was observed in situ during the study
      period.

PMID- 24865384
TI  - An assessment of contamination of the Fusaro Lagoon (Campania Province, southern
      Italy) by trace metals.
AB  - The Fusaro Lagoon is a shallow lagoon, located in SW Italy, largely influenced in
      the last decades by several anthropic impacts. The study examined the pollution
      status of the lagoon, during year 2011-2012 at nine sampling stations with the
      aim to find out proper measurements of water lagoon restoration. Concentrations
      of heavy metals (HMs) (aluminium [Al], barium [Ba], cadmium [Cd], copper [Cu],
      iron [Fe], manganese [Mn], vanadium [V] and zinc [Zn]) were examined in water,
      sediments and specimens of the ascidian Ciona intestinalis sp. A. Low levels of
      dissolved oxygen concentration were detected at many stations, with mean values
      of 5.2-6.4 mg L(-1). The redox potential of surface waters was also low, -2.7 to
      50.7 mV. Sediments possessed high organic matter content, 17.7-29.4%. In
      sediments, the mean Zn level, 251.4 mg kg(-1), was about sixfold higher than that
      recorded in year 2000 (38.5 mg kg(-1)) and considerably higher than that recorded
      in 2007 (191 mg kg(-1)). The mean levels of Cd were outstandingly high, with a
      mean value of 70.5 mg kg(-1), about 30- and 50-fold higher than those determined
      in 2000 and 2007, respectively. Cadmium (Cd), Cu and nickel (Ni) appeared in
      excess with respect to most current guidelines, reaching significant pollution
      levels. C. intestinalis sp. A was detected only at few stations, with metals
      accumulated preferentially in the body in respect to the tunic, from 1.2 times
      for Zn (178 mg kg(-1)) to 4.0 times for V (304 mg kg(-1)). Data suggests the
      necessity of an immediate action of eco-compatible interventions for
      environmental restoration.

PMID- 24865385
TI  - Quantitative tolerance values for common stream benthic macroinvertebrates in the
      Yangtze River Delta, Eastern China.
AB  - Aquatic organisms' tolerance to water pollution is widely used to monitor and
      assess freshwater ecosystem health. Tolerance values (TVs) estimated based on
      statistical analyses of species-environment relationships are more objective than
      those assigned by expert opinion. Region-specific TVs are the basis for
      developing accurate bioassessment metrics particularly in developing countries,
      where both aquatic biota and their responses to human disturbances have been
      poorly documented. We used principal component analysis to derive a synthetic
      gradient for four stressor variables (total nitrogen, total phosphorus, dissolved
      oxygen, and % silt) based on 286 sampling sites in the Taihu Lake and Qiantang
      River basins (Yangtze River Delta), China. We used the scores of taxa on the
      first principal component (PC1), which explained 49.8% of the variance, to
      estimate the tolerance values (TV(r)) of 163 macroinvertebrates taxa that were
      collected from at least 20 sites, 81 of which were not included in the Hilsenhoff
      TV lists (TV(h)) of 1987. All estimates were scaled into the range of 1-10 as in
      TV(h). Of all the taxa with different TVs, 46.3% of TV(r) were lower and 52.4%
      were higher than TV(h). TV(r) were significantly (p < 0.01, Fig. 2), but weakly
      (r(2) = 0.34), correlated with TVh. Seven biotic metrics based on TVr were more
      strongly correlated with the main stressors and were more effective at
      discriminating references sites from impacted sites than those based on TV(h).
      Our results highlight the importance of developing region-specific TVs for
      macroinvertebrate-based bioassessment and to facilitate assessment of streams in
      China, particularly in the Yangtze River Delta.

PMID- 24865387
TI  - Bilateral obturator pyomyositis with visceral involvement in an immunocompetent
      adult patient treated without surgery.
AB  - BACKGROUND: Primary pyomyositis is a rare bacterial infection that affects large
      muscle groups mainly in immunocompromised patients. Treatment options include
      antibiotic treatment with surgical or radiologic interventions. CASE: A 22-year
      old immunocompetent athlete was diagnosed with bilateral obturator muscle
      pyomyositis involving pelvic floor muscles and the urinary bladder after muscle
      injury during training. Intravenous antibiotic treatment was administered,
      resulting in eradication of the infection. CONCLUSION: This is the first case of
      bilateral obturator pyomyositis with coexisting involvement of pelvic floor
      muscles (levator ani) and viscera (urinary bladder) treated exclusively and with
      success by the administration of appropriate antibiotic therapy. A non-operative
      approach may could be attempted for the avoidance of postoperative morbidity and
      complications, especially when early clinical suspicion and diagnostic work-up
      lead to early diagnosis.

PMID- 24865386
TI  - Assessment of ammonium, nitrate, phosphate, and heavy metal pollution in
      groundwater from Amik Plain, southern Turkey.
AB  - Amik Plain is one of the most important agricultural areas of Turkey. Because the
      groundwater resources have been used not only for irrigation but also for
      drinking purpose, groundwater resources play a vital role in this area. However,
      there exist no or a very limited number of studies on groundwater quality and its
      physicochemical and heavy metal composition for Amik Plain. This study aimed to
      assess groundwater of Amik Plain in terms of human health and suitability for
      irrigation based on physicochemical variables, heavy metals, and their spatial
      distribution. A total of 92 groundwater samples were collected from wells and
      were analyzed for temperature (T), salt content (SC), dissolved oxygen (DO),
      ammonium (NH4(+)), nitrate (NO3(-)), and phosphorus (P) and such heavy metals as
      cadmium (Cd), cobalt (Co), chromium (Cr), copper (Cu), iron (Fe), manganese (Mn),
      nickel (Ni), lead (Pb), and zinc (Zn). The temperature, SC, DO, NH4(+), and NO3(
      ) parameters were measured in situ immediately with YSI Professional plus
      instrument (Pro Plus). Water depth was taken from owner of the wells. Heavy metal
      analyses were carried out in triplicate using inductively coupled atomic emission
      spectrometer (ICP-AES). The ICP-AES was calibrated for all the metals by running
      different concentrations of standard solutions. Descriptive statistical analyses
      were calculated to characterize distribution of physicochemical properties and
      heavy metal contents of groundwater. Correlation analysis was used to assess the
      possible relationships among heavy metals and physicochemical properties of the
      groundwater. Spatial variability in groundwater parameters were determined by
      geostatistical methods. Result shows that the highest and lowest coefficient of
      variation occurred for NO3(-) and T, respectively. Mean water table depth was
      92.1 m, and only 12 of all the samples exceeded the desirable limit of 50 mg/L
      for NO3(-) content. The metal concentrations showed a dominance in the order of
      Fe > Mn > Ni > Cr > Cu > Zn > Co > Cd > Pb. All the samples had much higher Cd
      concentration than the guideline value for drinking water while Cu and Fe
      concentrations were below the guideline limit recommended by WHO.

PMID- 24865388
TI  - Examining incentive design strategies for worksite wellness program engagement.
AB  - The objective was to examine employee engagement in worksite wellness activities
      at 2 large US companies that differed in engagement strategy and incentive plan.
      Inclusion criteria were US employees aged 18 to 65 who were eligible to receive
      wellness benefits throughout 2012. Company B's incentive was twice the dollar
      value of Company A's and produced higher engagement rates for the health
      assessment (HA; 26.1% vs. 24.4%, P<.001), and biometric screening (32.8% vs.
      25.4%, P<.001). Among the subgroup of employees who completed the HA and the
      biometric screening, 44.6% (N=2,309) at Company A engaged in at least 1 coaching
      session compared to 8.9% (N=594) at Company B. Fewer employees at Company A with
      high-risk cholesterol engaged in coaching compared to Company B (44.6% vs. 54.9%,
      P=.009). However, more Company A employees with high-risk blood pressure engaged
      in coaching compared to Company B (41.3% vs. 34.8%, P=.053). Company A engaged
      more obese employees compared to Company B (43.7% vs. 13.9%, P<.001), although
      obesity was not directly targeted at either company. Predictors of enrolling in
      coaching included being female, older age, higher education, and those not at
      high risk for stress, diet, and tobacco for Company A, and older age, and high
      risk for blood pressure, cholesterol, and obesity for Company B. A population
      approach to incentive design for program engagement engaged high-risk employees
      in coaching, and engaged a high proportion of employees not at high risk, but who
      can still be at risk for chronic diseases.

PMID- 24865389
TI  - Cognitive rehabilitation therapy after acquired brain injury in Argentina:
      psychosocial outcomes in connection with the time elapsed before treatment
      initiation.
AB  - PRIMARY OBJECTIVE: To examine the effect of cognitive rehabilitation therapy
      (CRT) on psychosocial outcomes in Argentinean patients with acquired brain injury
      (ABI), in connection with the time elapsed between injury and treatment
      initiation. RESEARCH DESIGN: Self-reported data from patients in a naturalistic
      setting was collected before and after CRT. METHODS AND PROCEDURE: An outpatient
      sample of 75 Spanish-speaking patients with cognitive disturbances secondary to
      ABI (49 male/26 female, age: 50.2 +/- 20.1 years; education 14.3 +/- 3.2 years)
      completed a set of scales on their daily living activities, memory self
      perception, quality-of-life and mood. Single and multi-group analyses were
      conducted, considering pre- and post- responses and the time elapsed between
      injury and treatment initiation. The influence of socio-demographic moderators
      was controlled during comparisons. MAIN RESULTS: Results suggest an improvement
      in several psychosocial indicators after treatment. Additionally, correlations
      and group comparisons showed greater improvement in subjective memory and quality
      of-life self-reports in patients who began treatment earlier than those who began
      treatment after a longer time period. CONCLUSIONS: Overall, results suggest that
      CRT is associated with positive results in different areas of the psychosocial
      domain and that post-injury time can mediate this effect.

PMID- 24865392
TI  - Metal and carbene organocatalytic relay activation of alkynes for stereoselective
      reactions.
AB  - Transition metal and organic catalysts have established their own domains of
      excellence. It has been expected that merging the two unique domains should
      provide complimentary or unprecedented opportunities in converting simple raw
      materials to functional products. N-heterocyclic carbenes alone are excellent
      organocatalysts. When used with transition metals such as copper, N-heterocyclic
      carbenes are routinely practiced as strong-coordinating ligands. Combination of
      an N-heterocyclic carbene and copper therefore typically leads to deactivation of
      either or both of the two catalysts. Here we disclose the direct merge of copper
      as a metal catalyst and N-heterocyclic carbenes as an organocatalyst for relay
      activation of alkynes. The reaction involves copper-catalysed activation of
      alkynes to generate ketenimine intermediates that are subsequently activated by
      an N-heterocyclic carbene organocatalyst for stereoselective reactions. Each of
      the two catalysts (copper metal catalyst and N-heterocyclic carbene
      organocatalyst) accomplishes its own missions in the activation steps without
      quenching each other. 

PMID- 24865391
TI  - Ablation of carious dental tissue using an ultrashort pulsed laser (USPL) system.
AB  - The aim of the study was to investigate the efficiency of caries removal
      employing an ultrashort pulsed laser (USPL) and to compare the results regarding
      to the ablation rate of sound enamel and dentin including surface texture. The
      study was performed with 59 freshly extracted carious human teeth. Two cavities
      with an edge length of 1 * 1 mm per tooth were created: one in the dental decay
      and one in sound hard tissue. For this purpose a 9-W Nd:YVO4 laser with a center
      wavelength of 1,064 nm and a pulse duration of 8 ps at a repetition rate of 500
      kHz was used. A scanner system moved the laser beam across the surface with a
      scan speed of 2,000 mm/s. Ablated volume and roughness R z of the cavity ground
      were measured using an optical profilometer. Subsequently, the specimens were cut
      to undecalcified sections for histological investigations. The removal of dental
      decay (dentin, 14.9 mm(3)/min; enamel, 12.8 mm(3)/min) was significantly higher
      (p < 0.05) compared to the removal of sound tissues (dentin, 4.2 mm(3)/min;
      enamel, 3.8 mm(3)/min). The arithmetic means of the surface roughness R z were
      8.5 MUm in carious enamel, 15.43 MUm in carious dentin, 4.83 MUm in sound enamel
      and 5.52 MUm in sound dentin. Light microscopic investigations did not indicate
      any side effects in the surrounding tissues. Regarding the ablation rate of
      dental decay using the USPL system, caries removal seems to be much more
      efficient for cavity preparation. 

PMID- 24865390
TI  - The posology of oseltamivir in infants with influenza infection using a
      population pharmacokinetic approach.
AB  - Infants are at increased risk for morbidity and mortality due to influenza. Until
      recently, few data were available with which to optimize oseltamivir dosing in
      this high-risk population. Here, data for 133 infants were pooled from two
      prospective pharmacokinetic/pharmacodynamic safety studies to develop a
      population pharmacokinetic model. A three-compartment model with allometric
      scaling of all clearance and volume parameters described the disposition of
      oseltamivir and its carboxylate metabolite (OC). Weight dependence, OC clearance,
      and volume of distribution increased linearly with age. Analyses showed no
      association between OC exposure and viral clearance, the development of
      resistance (phenotypic/genotypic), normalization of body temperature, or safety
      endpoints. Pharmacokinetic bridging showed that a 3 mg/kg dose yielded acceptable
      OC exposure and good tolerability while minimizing the risk of underexposure and
      resistance/treatment failure. These pharmacological analyses formed the basis of
      the US Food and Drug Administration's recent approval of oseltamivir treatment
      for infants with influenza aged as young as 2 weeks.

PMID- 24865393
TI  - Reconstructing past ecological networks: the reconfiguration of seed-dispersal
      interactions after megafaunal extinction.
AB  - The late Quaternary megafaunal extinction impacted ecological communities
      worldwide, and affected key ecological processes such as seed dispersal. The
      traits of several species of large-seeded plants are thought to have evolved in
      response to interactions with extinct megafauna, but how these extinctions
      affected the organization of interactions in seed-dispersal systems is poorly
      understood. Here, we combined ecological and paleontological data and network
      analyses to investigate how the structure of a species-rich seed-dispersal
      network could have changed from the Pleistocene to the present and examine the
      possible consequences of such changes. Our results indicate that the seed
      dispersal network was organized into modules across the different time periods
      but has been reconfigured in different ways over time. The episode of megafaunal
      extinction and the arrival of humans changed how seed dispersers were distributed
      among network modules. However, the recent introduction of livestock into the
      seed-dispersal system partially restored the original network organization by
      strengthening the modular configuration. Moreover, after megafaunal extinctions,
      introduced species and some smaller native mammals became key components for the
      structure of the seed-dispersal network. We hypothesize that such changes in
      network structure affected both animal and plant assemblages, potentially
      contributing to the shaping of modern ecological communities. The ongoing
      extinction of key large vertebrates will lead to a variety of context-dependent
      rearranged ecological networks, most certainly affecting ecological and
      evolutionary processes. 

PMID- 24865396
TI  - Differences of soil fertility in farmland occupation and supplement areas in the
      Taihu Lake watershed during 1985-2010.
AB  - Since the 1980s a series of farmland policies have been implemented in China to
      stabilize the balance of farmland quantity and quality against accelerating
      urbanization and industrialization processes. This paper aims to reveal
      differences of soil fertility in the farmland occupation area (FOA) and farmland
      supplement area (FSA). In 1985-2000 the decline of the FOA area was 181,000 ha,
      but the FSA rarely increased. In 2000-2010 the decline of the FOA area was
      824,800 ha, but the FSA increased dramatically. The accelerating loss process is
      closely related to urbanization and industrialization of the locations. Most
      occupied farmland was still located in the areas with higher soil fertility. The
      FOA in 1985-2000 had higher soil fertility than the FSA, but the FSA in 2000-2010
      significantly raised its soil fertility to close to the FOAs' level. The rate of
      excellent-good levels of the FOA in 2000-2010 decreased from 46.13% to 37.61%;
      The development model shifts and farmland policies implementation are the chief
      driving factors behind AFOS changes. The TDBF policy and the main function zoning
      project should continue to play an effective role in balancing the farmland
      system. 

PMID- 24865395
TI  - Oxidative stress of office workers relevant to tobacco smoking and inner air
      quality.
AB  - Studies have used 8-hydroxydeoxyguanosine (8-OHdG) as a biomarker to detect
      systemic oxidative DNA damage associated with oxidative stress. However, studies
      on the association between exposure to tobacco smoking and urinary 8-OHdgG give
      inconsistent results. Limited studies have estimated the oxidative stress among
      office workers. This study assessed the association between urinary 8-OHdG and
      cotinine for office workers.  Workers (389) including smokers, ex-smokers and non
      smokers from 87 offices at high-rise buildings in Taipei participated in this
      study with informed consent. Each participant completed a questionnaire and
      provided a spot urine specimen at the end of work day for measuring urinary 8
      OHdG and cotinine. The carbon dioxide (CO2) levels in workers' offices were also
      measured. The questionnaire reported socio-demographic characteristics, life
      styles and allergic history. The urinary 8-OHdG level increased with the cotinine
      level among participants (Spearmans' rho = 0.543, p < 0.001). The mean of urinary
      8-OHdG and cotinine was 5.81 +/- 3.53 MUg/g creatinine and 3.76 +/- 4.06 MUg/g
      creatinine, respectively. Comparing with non-smokers, the adjusted odds ratio
      (OR) of having urinary 8-OHdG greater than the median level of 4.99 MUg/g
      creatinine was 5.30 (95% confidence intervals (CI) = 1.30-21.5) for current
      smokers and 0.91 (95% CI = 0.34-2.43) for former smokers. We also found workers
      exposed to 1,000 ppm of CO2 at offices had an adjusted OR of 4.28 (95% CI = 1.12
      16.4) to have urinary 8-OHdG greater than 4.99 MUg/g creatinine, compared to
      those exposed to indoor CO2 under 600 ppm. In conclusion, urinary 8-OHdG could
      represent a suitable marker for measuring smoking and CO2 exposure for office
      workers. 

PMID- 24865394
TI  - Community-based recreational football: a novel approach to promote physical
      activity and quality of life in prostate cancer survivors.
AB  - As the number of cancer survivors continues to increase, there is an increasing
      focus on management of the long-term consequences of cancer including health
      promotion and prevention of co-morbidity. Prostate cancer is the most frequent
      type of cancer type in men and causes increased risk of heart disease, diabetes
      and osteoporosis. Epidemiological evidence points to a positive effect of regular
      physical activity on all-cause and prostate cancer mortality and current clinical
      evidence supports the use of exercise in cancer rehabilitation. However, the
      external validity of existing exercise studies is limited and the majority of
      prostate cancer survivors remain sedentary. Hence, novel approaches to evaluate
      and promote physical activity are warranted. This paper presents the rationale
      behind the delivery and evaluation of community-based recreational football
      offered in existing football clubs under the Danish Football Association to
      promote quality of life and physical activity adherence in prostate cancer
      survivors. The RE-AIM framework will be applied to evaluate the impact of the
      intervention including outcomes both at the individual and organizational level.
      By introducing community-based sport environments, the study offers a novel
      approach in the strive towards sustained physical activity adherence and
      accessibility in prostate cancer survivors. 

PMID- 24865397
TI  - Geospatial disparities and the underlying causes of major cancers for women in
      Taiwan.
AB  - Some specific types of cancer still pose a severe threat to the health of
      Taiwanese women. This study focuses on determining the geographical locations of
      hot spots and causal factors related to the major categories of cancers in
      Taiwanese women. Cancer mortality data from 1972 to 2001 of 346 townships in
      Taiwan were obtained from the Atlas of Cancer Mortality. Principal component
      analysis was conducted to determine the primary categories of female cancers. The
      spatial patterns of hot spots and cold spots for each major cancer category were
      identified using the local indicator of spatial association. Finally, the
      regional differences between the hot spots and cold spots were compared to
      confirm the possible factors causing cancer throughout Taiwan. A total of 21
      cancer types in women were divided into seven major categories, which accounted
      for 68.0% of the total variance. The results from the spatial autocorrelation
      analysis showed significant spatial clusters of the cancer categories. Based on
      the overall consistency of results between this study and those of previous
      research, this study further identified the high-risk locations and some specific
      risk factors for major cancer types among Taiwanese women. 

PMID- 24865398
TI  - Phthalate exposure and health-related outcomes in specific types of work
      environment.
AB  - Many toxic substances in the workplace can modify human health and quality of
      life and there is still insufficient data on respiratory outcomes in adults
      exposed to phthalates. The aim of this work was to assess in waste management
      workers from the Nitra region of Slovakia (n = 30) the extent of exposure to
      phthalates and health-related outcomes. Four urinary phthalate metabolites mono(2
      ethylhexyl) phthalate (MEHP), monobutyl phthalate (MnBP), monoethyl phthalate
      (MEP) and monoisononyl phthalate (MiNP) were determined by high-performance
      liquid chromatography with mass spectrometry (HPLC-MS/MS). Urinary concentration
      of MEHP was positively associated with ratio of forced expiratory volume in 1 s
      to forced vital capacity % (FEV1/FVC) (r = 0.431; p = 0.018) and MiNP with fat
      free mass index (FFMI) (r = 0.439; p = 0.015). The strongest predictor of
      pulmonary function was the pack/year index as smoking history that predicted a
      decrease of pulmonary parameters, the FEV1/FVC, % of predicted values of peak
      expiratory flow (PEF % of PV) and FEV1 % of PV. Unexpectedly, urinary MEHP and
      MINP were positively associated with pulmonary function expressed as PEF % of PV
      and FEV1/FVC. We hypothesize that occupational exposure to phthalates estimated
      from urinary metabolites (MEHP, MiNP) can modify pulmonary function on top of
      lifestyle factors. 

PMID- 24865399
TI  - Socioeconomic context and the food landscape in Texas: results from hotspot
      analysis and border/non-border comparison of unhealthy food environments.
AB  - PURPOSE: The purpose of this paper is to describe the food landscape of Texas
      using the CDC's Modified Retail Food Environment (mRFEI) and to make comparisons
      by border/non-border. METHODS: The Modified Retail Food Environment index (mRFEI
      (2008)) is an index developed by the CDC that measures what percent of the total
      food vendors in a census track sell healthy food. The range of values is 0
      (unhealthy areas with limited access to fruits and vegetables) to (100-Healthy).
      These data were linked to 2010 US Census socioeconomic and ethnic concentration
      data. Spatial analysis and GIS techniques were applied to assess the differences
      between border and non-border regions. Variables of interest were mRFEI score,
      median income, total population, percent total population less than five years,
      median age, % receiving food stamps, % Hispanic, and % with a bachelor degree.
      RESULTS: Findings from this study reveal that food environment in Texas tends to
      be characteristic of a "food desert". Analysis also demonstrates differences by
      border/non-border location and percent of the population that is foreign born and
      by percent of families who receive food stamps. CONCLUSIONS: Identifying the
      relationship between socioeconomic disparity, ethnic concentration and mRFEI
      score could be a fundamental step in improving health in disadvantage
      communities, particularly those on the Texas-Mexico border.

PMID- 24865400
TI  - Differential inductions of phenylalanine ammonia-lyase and chalcone synthase
      during wounding, salicylic acid treatment, and salinity stress in safflower,
      Carthamus tinctorius.
AB  - Safflower (Carthamus tinctorius L.) serves as a reference dicot for investigation
      of defence mechanisms in Asteraceae due to abundant secondary metabolites and
      high resistance/tolerance to environmental stresses. In plants, phenylpropanoid
      and flavonoid pathways are considered as two central defence signalling cascades
      in stress conditions. Here, we describe the isolation of two major genes in these
      pathways, CtPAL (phenylalanine ammonia-lyase) and CtCHS (chalcone synthase) in
      safflower along with monitoring their expression profiles in different stress
      circumstances. The aa (amino acid) sequence of isolated region of CtPAL possesses
      the maximum identity up to 96% to its orthologue in Cynara scolymus, while that
      of CtCHS retains the highest identity to its orthologue in Callistephus chinensis
      up to 96%. Experiments for gene expression profiling of CtPAL and CtCHS were
      performed after the treatment of seedlings with 0.1 and 1 mM SA (salicylic acid),
      wounding and salinity stress. The results of semi-quantitative RT-PCR revealed
      that both CtPAL and CtCHS genes are further responsive to higher concentration of
      SA with dissimilar patterns. Regarding wounding stress, CtPAL gets slightly
      induced upon injury at 3 hat (hours after treatment) (hat), whereas CtCHS gets
      greatly induced at 3 hat and levels off gradually afterward. Upon salinity
      stress, CtPAL displays a similar expression pattern by getting slightly induced
      at 3 hat, but CtCHS exhibits a biphasic expression profile with two prominent
      peaks at 3 and 24 hat. These results substantiate the involvement of
      phenylpropanoid and particularly flavonoid pathways in safflower during wounding
      and especially salinity stress.

PMID- 24865401
TI  - The relationship between serial [(18) F]PBR06 PET imaging of microglial
      activation and motor function following stroke in mice.
AB  - PURPOSE: Using [(18) F]PBR06 positron emission tomography (PET) to characterize
      the time course of stroke-associated neuroinflammation (SAN) in mice, to evaluate
      whether brain microglia influences motor function after stroke, and to
      demonstrate the use of [(18) F]PBR06 PET as a therapeutic assessment tool.
      PROCEDURES: Stroke was induced by transient middle cerebral artery occlusion
      (MCAO) in Balb/c mice (control, stroke, and stroke with poststroke minocycline
      treatment). [18 F]PBR06 PET/CT imaging, rotarod tests, and immunohistochemistry
      (IHC) were performed 3, 11, and 22 days poststroke induction (PSI). RESULTS: The
      stroke group exhibited significantly increased microglial activation, and
      impaired motor function. Peak microglial activation was 11 days PSI. There was a
      strong association between microglial activation, motor function, and microglial
      protein expression on IHC. Minocycline significantly reduced microglial
      activation and improved motor function by day 22 PSI. CONCLUSION: [18 F]PBR06 PET
      imaging noninvasively characterizes the time course of SAN, and shows increased
      microglial activation is associated with decreased motor function.

PMID- 24865403
TI  - Extracranial hypothermia during cardiac arrest and cardiopulmonary resuscitation
      is neuroprotective in vivo.
AB  - There is increasing evidence that ischemic brain injury is modulated by
      peripheral signaling. Peripheral organ ischemia can induce brain inflammation and
      injury. We therefore hypothesized that brain injury sustained after cardiac
      arrest (CA) is influenced by peripheral organ ischemia and that peripheral organ
      protection can reduce brain injury after CA and cardiopulmonary resuscitation
      (CPR). Male C57Bl/6 mice were subjected to CA/CPR. Brain temperature was
      maintained at 37.5 degrees C +/- 0.0 degrees C in all animals. Body temperature
      was maintained at 35.1 degrees C +/- 0.1 degrees C (normothermia) or 28.8 degrees
      C +/- 1.5 degrees C (extracranial hypothermia [ExHy]) during CA. Body temperature
      after resuscitation was maintained at 35 degrees C in all animals. Behavioral
      testing was performed at 1, 3, 5, and 7 days after CA/CPR. Either 3 or 7 days
      after CA/CPR, blood was analyzed for serum urea nitrogen, creatinine, alanine
      aminotransferase, aspartate aminotransferase, and interleukin-1beta; mice were
      euthanized; and brains were sectioned. CA/CPR caused peripheral organ and brain
      injury. ExHy animals experienced transient reduction in brain temperature after
      resuscitation (2.1 degrees C +/- 0.5 degrees C for 4 minutes). Surprisingly, ExHy
      did not change peripheral organ damage. In contrast, hippocampal injury was
      reduced at 3 days after CA/CPR in ExHy animals (22.4% +/- 6.2% vs. 45.7% +/-
      9.1%, p=0.04, n=15/group). This study has two main findings. Hypothermia limited
      to CA does not reduce peripheral organ injury. This unexpected finding suggests
      that after brief ischemia, such as during CA/CPR, signaling or events after
      reperfusion may be more injurious than those during the ischemic period. Second,
      peripheral organ hypothermia during CA reduces hippocampal injury independent of
      peripheral organ protection. While it is possible that this protection is due to
      subtle differences in brain temperature during early reperfusion, we speculate
      that additional mechanisms may be involved. Our findings add to the growing
      understanding of brain-body cross-talk by suggesting that peripheral
      interventions can protect the brain even if peripheral organ injury is not
      altered.

PMID- 24865402
TI  - In vitro and in vivo characterization of two C-11-labeled pet tracers for
      vesicular acetylcholine transporter.
AB  - PURPOSE: The vesicular acetylcholine transporter (VAChT) is a specific biomarker
      for imaging presynaptic cholinergic neurons. Herein, two potent and selective
      (11)C-labeled VAChT inhibitors were evaluated in rodents and nonhuman primates
      for imaging VAChT in vivo. PROCEDURES: For both (-)-[(11)C]2 and (-)-[(11)C]6,
      biodistribution, autoradiography, and metabolism studies were performed in male
      Sprague Dawley rats. Positron emission tomography (PET) brain studies with (-)
      [(11)C]2 were performed in adult male cynomolgus macaques; 2 h dynamic data was
      acquired, and the regions of interest were drawn by co-registration of the PET
      images with the MRI. RESULTS: The resolved enantiomers (-)-2 and (-)-6 were very
      potent and selective for VAChT in vitro (K i  < 5 nM for VAChT with >35-fold
      selectivity for VAChT vs. sigma receptors); both radioligands, (-)-[(11)C]2 and (
      )-[(11)C]6, demonstrated high accumulation in the VAChT-enriched striatum of
      rats. (-)-[(11)C]2 had a higher striatum to cerebellum ratio of 2.4-fold at 60
      min; at 30 min, striatal uptake reached 0.550 +/- 0.086 %ID/g. Uptake was also
      specific and selective; following pretreatment with (+/-)-2, striatal uptake of (
      )-[(11)C]2 in rats at 30 min decreased by 50 %, while pretreatment with a potent
      sigma ligand had no significant effect on striatal uptake in rats. In addition, (
      )-[(11)C]2 displayed favorable in vivo stability in rat blood and brain. PET
      studies of (-)-[(11)C]2 in nonhuman primates indicate that it readily crosses the
      blood-brain barrier (BBB) and provides clear visualization of the striatum;
      striatal uptake reaches the maximum at 60 min, at which time the target to
      nontarget ratio reached ~2-fold. CONCLUSIONS: The radioligand (-)-[(11)C]2 has
      high potential to be a suitable PET radioligand for imaging VAChT in the brain of
      living subjects.

PMID- 24865406
TI  - A qualitative description of falls in a neuro-rehabilitation unit: the use of a
      standardised fall report including the International Classification of
      Functioning (ICF) to describe activities and environmental factors.
AB  - PURPOSE: Falls are a recognised problem for people with long-term neurological
      conditions but less is known about fall risk in young adults. This study
      describes fallers' and falls' characteristics in adults less than 60 years old,
      in a neuro-rehabilitation unit. METHODS: This single-centre, longitudinal,
      observational study included 114 consecutive admissions to a UK neuro
      rehabilitation unit over 20 months. The demographic and clinical characteristics
      of eligible patients included age, sex, diagnosis, hospital length of stay and
      the Functional Independence Measure (FIM). Falls were recorded prospectively in a
      fall report, using the activities and environmental domains of the International
      Classification of Functioning (ICF). RESULTS: A total of 34 (30%) patients
      reported a fall, with 50% experiencing more than one fall. The majority of falls
      (60%) occurred during the first 2 weeks, during day-time (90%) and during mobile
      activities (70%). Overall, falls rate (95% confidence interval) was 1.33 (1.04 to
      1.67) per 100 d of patient hospital stay. Factors associated with increased falls
      included becoming a walker during admission or being cognitively impaired. There
      were no serious fall-related injuries. CONCLUSION: The first 2 weeks of admission
      is a high risk time for fallers, in particular those who become walkers or are
      cognitively impaired. Prevention policies should be put in place based on fall
      characteristics. Implications for Rehabilitation The ICF is a valuable instrument
      for describing subject and environmental factors during a fall-event. Falls are
      frequent events but do not usually cause serious injuries during inpatient
      rehabilitation. There is an increased fall risk for subjects with cognitive
      impairments or those relearning how to walk.

PMID- 24865404
TI  - Afghanistan's basic package of health services: its development and effects on
      rebuilding the health system.
AB  - In 2001, Afghanistan's Ministry of Public Health inherited a devastated health
      system and some of the worst health statistics in the world. The health system
      was rebuilt based on the Basic Package of Health Services (BPHS). This paper
      examines why the BPHS was needed, how it was developed, its content and the
      changes resulting from the rebuilding. The methods used for assessing change were
      to review health outcome and health system indicator changes from 2004 to 2011
      structured along World Health Organisation's six building blocks of health system
      strengthening. BPHS implementation contributed to success in improving health
      status by translating policy and strategy into practical interventions, focusing
      health services on priority health problems, clearly defining the services to be
      delivered at different service levels and helped the Ministry to exert its
      stewardship role. BPHS was expanded nationwide by contracting out its provision
      of services to non-governmental organisations. As a result, access to and
      utilisation of primary health care services in rural areas increased dramatically
      because the number of BPHS facilities more than doubled; access for women to
      basic health care improved; more deliveries were attended by skilled personnel;
      supply of essential medicines increased; and the health information system became
      more functional. 

PMID- 24865407
TI  - Sick leave diagnoses and return to work: a Swedish register study.
AB  - PURPOSE: To provide a detailed description of return to work (RTW) for different
      diagnoses. METHODS: A sample of 617,611 cases of sick leave with minimum duration
      of 14 days started in 2009 and 2010 was followed for 450 days. Data on sick leave
      episodes, diagnosis (ICD-10 codes on 3-digit level) and background factors were
      retrieved from Swedish National Social Insurance registers. RTW was analysed with
      Cox proportional hazard regression with separate analyses for women and men.
      RESULTS: The diseases with the lowest RTW rates were present within malign
      neoplasms, severe mental disorders and severe cardiovascular diseases. High-RTW
      rates were present for infectious respiratory diseases, viral infections and less
      severe cardiovascular diseases. There were distinct differences across diagnoses
      within all diagnosis chapters. This also holds for mental disorders and
      musculoskeletal diseases, which are the most common causes of sick leave. The
      results for women and men across different diseases and disorders were strikingly
      similar. CONCLUSIONS: Systematic use of standard information such as detailed
      sick listing diagnosis could, at low-additional cost, pinpoint cases at risk for
      prolonged sick leave. The use of broad diagnosis categories in sick leave
      research may be questioned since there are distinct differences in RTW within ICD
      10 chapters.

PMID- 24865408
TI  - A proteomics approach to the identification of plasma biomarkers for latent
      tuberculosis infection.
AB  - A proteomic analysis was performed to screen the potential latent tuberculosis
      infection (LTBI) biomarkers. A training set of spectra was used to generate
      diagnostic models, and a blind testing set was used to determine the accuracy of
      the models. Candidate peptides were identified using nano-liquid chromatography
      electrospray ionization-tandem mass spectrometry. Based on the training set
      results, 3 diagnostic models recognized LTBI subjects with good cross-validation
      accuracy. In the blind testing set, LTBI subjects could be identified with
      sensitivities and specificities of 85.20% to 88.90% and 85.7% to 100%,
      respectively. Additionally, 14 potential LTBI biomarkers were identified, and all
      proteins were identified for the first time through proteomics in the plasma of
      healthy, latently infected individuals. In all, proteomic pattern analyses can
      increase the accuracy of LTBI diagnosis, and the data presented here provide
      novel insights into potential mechanisms involved in LTBI. 

PMID- 24865409
TI  - Association between individual and geographic factors and nonadherence to
      mammography screening guidelines.
AB  - BACKGROUND: This study investigates factors that are associated with nonadherence
      to mammography screening guidelines in Utah, a state where mammography screening
      rates have remained consistently lower than national averages. METHODS: We
      examined data on reported mammography use among women aged 40-74 years from the
      2008 and 2010 Utah Behavioral Risk Factor Surveillance System (n=5,197, weighted
      n=417,064). Logistic regression models were used to estimate the effects of
      individual-level and geographic (travel time to nearest mammography facility,
      geographic accessibility, and rural/urban residence) factors on the odds of a
      woman not reporting receiving a mammogram in the last 2 years. RESULTS: In 2008
      and 2010, a disproportionate number of women aged 40-49 (43.1%, 95% confidence
      interval [CI] 39.9%-46.3%) reported not receiving a mammogram within the last 2
      years compared to women 50-74 (26.8%, 95% CI 24.9%-28.7%). None of the geographic
      factors were significant predictors of screening adherence. Based on covariate
      adjusted models, statistically significant (p<0.05) factors associated with
      increased odds of not receiving mammogram within the last 2 years included not
      having a regular physician, no health insurance, being aged 40-49, income less
      than $25,000, and the presence of three or more children in the home. CONCLUSION:
      Mammography screening efforts in Utah should focus on improving access to
      insurance or a regular source of health care. Future research should also
      consider how best to address extreme time demands and competing priorities that
      present potential barriers for women with large families, resulting in lower
      screening levels among these women.

PMID- 24865410
TI  - Soil-transmitted helminth prevalence and infection intensity among geographically
      and economically distinct Shuar communities in the Ecuadorian Amazon.
AB  - Soil-transmitted helminth (STH) infections can result in a variety of negative
      health outcomes (e.g., diarrhea, nutritional deficiencies). Market integration
      (MI; participation in market-based economies) has been suggested to alter levels
      of STH exposure due to associated changes in diet, sanitation, and behavior, but
      the effects are complicated and not well understood. Some effects of economic
      development result in decreased exposure to certain pathogens, and other factors
      can lead to higher pathogen exposure. With geographic location used as a proxy,
      the present study investigates the effects of economic development on parasite
      load among an indigenous population at multiple points along the spectrum of MI.
      This research has many implications for public health, including an increased
      understanding of how social and economic changes alter disease risk around the
      world and how changing parasite load affects other health outcomes (i.e.,
      allergy, autoimmunity). Specifically, this study examines the prevalence of
      intestinal helminths among the Shuar, an indigenous group in the Morona-Santiago
      region of Ecuador, from 2 geographically/economically separated areas, with the
      following objectives: (1) report STH infection prevalence and intensity among
      Shuar; (2) explore STH infection prevalence and intensity as it relates to age
      distribution in the Shuar population; (3) compare STH infection patterns in
      geographically and economically separated Shuar communities at different levels
      of MI. Kato-Katz thick smears were made from fresh stool samples and examined to
      determine STH presence/intensity. Results indicate that 65% of the 211
      participants were infected with at least 1 STH. Twenty-five percent of the sample
      had coinfections with at least 2 species of helminth. Infection was more common
      among juveniles (<15 yr) than adults. Infection prevalence and intensity was
      highest among more isolated communities with less market access. This study
      documents preliminary associations between STH infection and exposure to MI, with
      implications for public health research and interventions. 

PMID- 24865411
TI  - Biochemical characterization of a Caspase-3 far-red fluorescent probe for non
      invasive optical imaging of neuronal apoptosis.
AB  - Apoptosis is a regulated process, leading to cell death, which is involved in
      several pathologies including neurodegenerative diseases and stroke. Caspase-3 is
      a key enzyme of the apoptotic pathway and is considered as a major target for the
      treatment of abnormal cell death. Sensitive and non-invasive methods to monitor
      caspase-3 activity in cells and in the brain of living animals are needed to test
      the efficiency of novel therapeutic strategies. In the present study, we have
      biochemically characterized a caspase-3 far-red fluorescent probe, QCASP3.2, that
      can be used to detect apoptosis in vivo. The specificity of cleavage of QCASP3.2
      was demonstrated using recombinant caspases and protease inhibitors. The
      functionality of the probe was also established in cerebellar neurons cultured in
      apoptotic conditions. QCASP3.2 did not exhibit any toxicity and appeared to
      accurately reflect the induction and inhibition of caspase activity by H2O2 and
      PACAP, respectively, both in cell lysates and in cultured neurons. Finally,
      intravenous injection of the probe after cerebral ischemia revealed activation of
      caspase-3 in the infarcted hemisphere. Thus, the present study demonstrates that
      QCASP3.2 is a suitable probe to monitor apoptosis both in vitro and in vivo and
      illustrates some of the possible applications of this caspase-3 fluorescent
      probe. 

PMID- 24865412
TI  - Incidence and clinical management of oral human papillomavirus infection in men:
      a series of key short messages.
AB  - Oral human papillomavirus (HPV) infections are less prevalent than genital and
      anal infections. However, the incidence of oropharyngeal squamous cell carcinomas
      has increased significantly over the last 2 decades in several countries. At
      least 90% of these cancers are associated with oncogenic type HPV16. Oral HPV
      infections are notably more frequent in men than in women, and the incidence of
      HPV-positive oropharyngeal squamous cell carcinomas has increased, predominantly
      among mid-adult men. Nevertheless, little is known about the progression of oral
      HPV infection to cancer, and it remains unclear which medical interventions
      should be applied to modify the natural history of the disease. This narrative
      review aimed at non-experts in HPV infection provides an update on oral HPV
      infection and its clinical management in men. Furthermore, using the cervix as a
      reference anatomical site, the lessons learned from investigations on cervical
      HPV infection are also addressed. 

PMID- 24865414
TI  - Phenotypes of Escherichia coli isolated from urine: Differences between extended
      spectrum beta-lactamase producers and sensitive strains.
AB  - BACKGROUND: Escherichia coli is a frequent causative agent of urinary tract
      infections, and increasing resistance of E. coli to antimicrobials presents a
      growing challenge. METHODS: Here we compare phenotypes of extended-spectrum beta
      lactamase (ESBL) producers (n = 220) with a control group of sensitive strains
      (non-ESBL producers; n = 150). For each strain, we assessed the presence of O25
      antigen, hemolysis, biofilm production, sensitivity to antibiotics, and
      biochemical profile. RESULTS: Compared to the control group, ESBL producers were
      more frequently O25 positive (6.0% vs. 42.3%) and less frequently hemolytic
      (34.7% vs. 6.4%). Comparison of biofilm production in brain-heart infusion (BHI)
      and in BHI with 4% glucose supplementation showed that ESBL-positive strains
      produced biofilm in BHI with glucose less intensely than the control group (p <
      0.05). Most ESBL producers were ciprofloxacin-resistant (91.8%). Biochemical
      analyses revealed that ESBL producers more frequently utilized inositol,
      ornithine, sorbitol, melibiose, and saccharose, whereas the control group more
      frequently used esculin, lysine, arginine, and dulcitol. The control group
      strains with O25 antigen were more commonly resistant to ciprofloxacin (p <
      0.05). Pulsed-field gel electrophoresis results showed higher variability among
      the control group of sensitive strains. CONCLUSION: These findings suggest a
      potential to detect ESBL strains based on virulence factors and biochemical
      properties, which could be useful in shaping proper empiric antimicrobial
      therapy, and for initiating such therapy as soon as possible.

PMID- 24865415
TI  - Kinetic study of the binding of triplex-forming oligonucleotides containing
      partial cationic modifications to double-stranded DNA.
AB  - Several triplex-forming oligonucleotides (TFOs) partially modified with 2'-O-(2
      aminoethyl)- or 2'-O-(2-guanidinoethyl)-nucleotides were synthesized and their
      association rate constants (kon) with double-stranded DNA were estimated by UV
      spectrophotometry. Introduction of cationic modifications in the 5'-region of the
      TFOs significantly increased the kon values compared to that of natural TFO,
      while no enhancement in the rate of triplex DNA formation was observed when the
      modifications were in the middle and at the 3'-region. The kon value of a TFO
      with three adjacent cationic modifications at the 5'-region was found to be 3.4
      times larger than that of a natural one. These results provide useful information
      for overcoming the inherent sluggishness of triplex DNA formation. 

PMID- 24865413
TI  - Sertraline induces endoplasmic reticulum stress in hepatic cells.
AB  - Sertraline is used for the treatment of depression, and is also used for the
      treatment of panic, obsessive-compulsive, and post-traumatic stress disorders.
      Previously, we have demonstrated that sertraline caused hepatic cytotoxicity,
      with mitochondrial dysfunction and apoptosis being underlying mechanisms. In this
      study, we used microarray and other biochemical and molecular analyses to
      identify endoplasmic reticulum (ER) stress as a novel molecular mechanism. HepG2
      cells were exposed to sertraline and subjected to whole genome gene expression
      microarray analysis. Pathway analysis revealed that ER stress is among the
      significantly affected biological changes. We confirmed the increased expression
      of ER stress makers by real-time PCR and Western blots. The expression of typical
      ER stress markers such as PERK, IRE1alpha, and CHOP was significantly increased.
      To study better ER stress-mediated drug-induced liver toxicity; we established in
      vitro systems for monitoring ER stress quantitatively and efficiently, using
      Gaussia luciferase (Gluc) and secreted alkaline phosphatase (SEAP) as ER stress
      reporters. These in vitro systems were validated using well-known ER stress
      inducers. In these two reporter assays, sertraline inhibited the secretion of
      Gluc and SEAP. Moreover, we demonstrated that sertraline-induced apoptosis was
      coupled to ER stress and that the apoptotic effect was attenuated by 4
      phenylbutyrate, a potent ER stress inhibitor. In addition, we showed that the
      MAP4K4-JNK signaling pathway contributed to the process of sertraline-induced ER
      stress. In summary, we demonstrated that ER stress is a mechanism of sertraline
      induced liver toxicity. 

PMID- 24865416
TI  - Marine spongian sesquiterpene phenols, dictyoceratin-C and smenospondiol, display
      hypoxia-selective growth inhibition against cancer cells.
AB  - In the course of our search for hypoxia-selective growth inhibitors against
      cancer cells, a sesquiterpene phenol, dictyoceratin-C (1), was isolated from the
      Indonesian marine sponge of Dactylospongia elegans under the guidance of the
      constructed bioassay. Dictyoceratin-C (1) inhibited proliferation of human
      prostate cancer DU145 cells selectively under hypoxic condition in a dose
      dependent manner at the concentrations ranging from 1.0 to 10 MUM. The subsequent
      structure-activity relationship study using nine sesquiterpene phenol/quinones (2
      10), which were isolated from marine sponge, was executed. We found that
      smenospondiol (2) also exhibited the similar hypoxia-selective growth inhibitory
      activity against DU145 cells, and the para-hydroxybenzoyl ester moiety would be
      important for hypoxia-selective growth inhibitory activity of 1. In addition, the
      mechanistic analysis of dictyoceratin-C (1) revealed that the 10 MUM of 1
      inhibited accumulation of Hypoxia-Inducible Factor-1alpha under hypoxic
      condition.

PMID- 24865417
TI  - Repetitive transcranial magnetic stimulation increases the corticospinal
      inhibition and the brain-derived neurotrophic factor in chronic myofascial pain
      syndrome: an explanatory double-blinded, randomized, sham-controlled trial.
AB  - Chronic myofascial pain syndrome has been related to defective descending
      inhibitory systems. Twenty-four females aged 19 to 65 years with chronic
      myofascial pain syndrome were randomized to receive 10 sessions of repetitive
      transcranial magnetic stimulation (rTMS) (n = 12) at 10 Hz or a sham intervention
      (n = 12). We tested if pain (quantitative sensory testing), descending inhibitory
      systems (conditioned pain modulation [quantitative sensory testing + conditioned
      pain modulation]), cortical excitability (TMS parameters), and the brain-derived
      neurotrophic factor (BDNF) would be modified. There was a significant interaction
      (time vs group) regarding the main outcomes of the pain scores as indexed by the
      visual analog scale on pain (analysis of variance, P < .01). Post hoc analysis
      showed that compared with placebo-sham, the treatment reduced daily pain scores
      by -30.21% (95% confidence interval = -39.23 to -21.20) and analgesic use by 
      44.56 (-57.46 to -31.67). Compared to sham, rTMS enhanced the corticospinal
      inhibitory system (41.74% reduction in quantitative sensory testing + conditioned
      pain modulation, P < .05), reduced the intracortical facilitation in 23.94% (P =
      .03), increased the motor evoked potential in 52.02% (P = .02), and presented
      12.38 ng/mL higher serum BDNF (95% confidence interval = 2.32-22.38). No adverse
      events were observed. rTMS analgesic effects in chronic myofascial pain syndrome
      were mediated by top-down regulation mechanisms, enhancing the corticospinal
      inhibitory system possibly via BDNF secretion modulation. PERSPECTIVE: High
      frequency rTMS analgesic effects were mediated by top-down regulation mechanisms
      enhancing the corticospinal inhibitory, and this effect involved an increase in
      BDNF secretion.

PMID- 24865418
TI  - Increased expression of Toll-like receptors (TLRs) 7 and 9 and other cytokines in
      systemic lupus erythematosus (SLE) patients: ethnic differences and potential new
      targets for therapeutic drugs.
AB  - Increased expression of pro-inflammatory cytokines such as interferon, tumor
      necrosis factors (TNFs) and specific interleukins (ILs) has been found in a
      number of autoimmune diseases, including systemic lupus erythematous (SLE). These
      cytokines are induced by toll-like receptors (TLRs). Toll-like receptors are
      activated in response to accumulation of apoptotic bodies. These receptors play
      critical roles in innate immune systems. Increased levels of interferon-alpha
      (INF-alpha) have also been found in many SLE patients and often correlate with
      disease severity. The objectives of this study were to examine the expression of
      selected TLRs and cytokines that have been identified in animal models and some
      limited human studies in a group of African Americans (AA) and European Americans
      (EA) women with lupus in comparison to age-matched non-lupus women. Blood samples
      were consecutively obtained by informed consent from 286 patients, 153 lupus and
      136 non-lupus, seen in the rheumatology clinics at East Carolina University.
      Cytokines were analyzed from blood serum using enzyme linked immunoassay (ELISA)
      for IL-6 and INF-alpha. Total RNA was isolated, using a Paxgene kit, from
      peripheral blood mononuclear cells of African American and European American
      women blood samples. Quantitative real-time PCR using the CFX real-time system
      was conducted on all samples to determine TLRs 7 and 9, as well as INF-alpha
      expression. Toll-like receptor 7 (p<0.01) and 9 (p=0.001) expression levels were
      significantly increased in lupus patients compared to age-matched controls.
      African American women with lupus had a 2-fold increase in TLR-9 expression level
      when compared to their healthy controls or European American lupus patients.
      However, there was no ethnic difference in expression of TLR-7 in lupus patients.
      INF-alpha expression was significantly higher in lupus patients (p<0.0001) and
      also showed ethnic difference in expression. Serum levels revealed significant
      increases in expression of IL-6, IFN-gamma and TNF-alpha in lupus patients
      compared to non-lupus patients. African American women with lupus had
      significantly higher serum levels of IL-6 and TNF-alpha. African American women
      with lupus demonstrated increased levels of specific pro-inflammatory cytokines
      and Toll-like receptors when compared to EA women. Increased expression in these
      lupus patients provides an opportunity for targeting with antagonist as a new
      therapy for systemic lupus erythematous. 

PMID- 24865419
TI  - RNA-seq profiles from grass carp tissues after reovirus (GCRV) infection based on
      singular and modular enrichment analyses.
AB  - Hemorrhagic disease of the grass carp, Ctenopharyngodon idella, is a fatal
      disease in fingerlings and yearlings caused by a reovirus, GCRV. RNA-seq data
      from four diseased grass carp tissues (gill, intestine, liver and spleen) were
      obtained at 2h before and six times after (2h, 24h, 48h, 72h, 96h and 120h) GCRV
      challenge. A total of 7.25+/-0.18 million (M) clean reads and 3.53+/-0.37M unique
      reads were obtained per RNA-seq analysis. Compared with controls, there were 9060
      unique differentially expressed genes (DEGs) in the four tissues at the six time
      points post-GCRV challenge. Hierarchical clustering analysis of the DEGs showed
      that the data from the six time points fell into three branches: 2h, 24h/48h, and
      72h/96h/120h. Singular (SEA) and modular enrichment analyses of DEGs per RNA-seq
      dataset were performed based on gene ontology. The results showed that immune
      responses occurred in all four tissues, indicating that GCRV probably does not
      target any tissue specifically. Moreover, during the course of disease,
      disturbances were observed in lipid and carbohydrate metabolism in each of the
      organs. SEA of DEGs based on the Kyoto Encyclopedia of Genes and Genomes database
      was also performed, and this indicated that the complement system and cellular
      immunity played an important role during the course of hemorrhagic disease. The
      qPCR of pooled samples of duplicate challenge experiment were used to confirm our
      RNA-seq approach. 

PMID- 24865420
TI  - Tumor-suppressing 15-lipoxygenase-2: time for prime time?

PMID- 24865421
TI  - Utility of red blood cell acetylcholinesterase measurement in mechanically
      ventilated subjects after organophosphate poisoning.
AB  - BACKGROUND: Many patients with organophosphate poisoning require mechanical
      ventilation. Muscle acetylcholinesterase (AChE) activity determines the
      impairment of muscle force generation, and red blood cell (RBC) AChE has been
      regarded as a surrogate for muscle AChE in organophosphate poisoning. Therefore,
      this study was conducted to investigate whether RBC AChE at presentation can
      predict the duration of mechanical ventilatory support and whether RBC AChE at
      weaning can predict weaning trial outcomes in patients on mechanical ventilation
      for organophosphate poisoning. METHODS: This retrospective observational case
      series identified 74 patients with a history of mechanical ventilation secondary
      to organophosphate poisoning and whose RBC AChE levels were available at
      presentation to the emergency department, at 24 h of presentation, or at weaning.
      Data were collected for plasma cholinesterase assay results, weaning outcome,
      duration of mechanical ventilation, and details of patient management (including
      ICU stay and amount of atropine and pralidoxime administered). RESULTS: RBC AChE
      activity levels at presentation and at 24 h of presentation had a negative
      correlation with duration of mechanical ventilation in subjects who ingested
      dimethyl organophosphate, but this correlation was not observed for those who had
      ingested diethyl or unclassified organophosphate. The optimal cutoff value of RBC
      AChE activity at presentation for predicting mechanical ventilation for < 7 d was
      1,330 U/L in subjects intoxicated with dimethyl organophosphate. However, there
      was no difference in RBC AChE activity at the time of weaning trial between
      successful and failed weaning events, regardless of the chemical formulation of
      organophosphate. CONCLUSIONS: We conclude that RBC AChE activity within 24 h of
      presentation can help predict the duration of mechanical ventilation for dimethyl
      organophosphate intoxication; however, RBC AChE activity at the time of weaning
      trial may not be a suitable parameter for predicting a patient's ability to be
      weaned from mechanical ventilation.

PMID- 24865422
TI  - In vitro evaluation of aerosol delivery by different nebulization modes in
      pediatric and adult mechanical ventilators.
AB  - BACKGROUND: Aerosol delivery through mechanical ventilation is influenced by the
      type of aerosol generator, pattern of nebulization, and a patient's breathing
      pattern. This study compares the efficiency of pneumatic nebulization modes
      provided by a ventilator with adult and pediatric in vitro lung models. METHODS:
      Three pneumatic nebulization modes (inspiratory intermittent [IIM], continuous
      [CM], and expiratory intermittent [EIM]) provided by the Galileo Gold ventilator
      delivered medical aerosol to collection filters distal to an endotracheal tube
      with adult and pediatric test lungs. A unit dose of 5 mg/2.5 mL albuterol was
      diluted into 4 mL with distilled water and added to a jet nebulizer. The
      nebulizer was placed proximal to the ventilator, 15 cm from the inlet of the
      heated humidifier chamber with a T-piece and corrugated aerosol tubing and
      powered by gas from the ventilator in each of the 3 modes. Time for nebulization
      was recorded in minutes. Albuterol samples collected in the inhalation filter,
      nebulizer, T-piece, and corrugated tubing were eluted with distilled water and
      analyzed with a spectrophotometer. RESULTS: The inhaled drug, as a percentage of
      total dose in both lung models, was 5.1-7.5%, without statistical significance
      among the 3 modes. Median nebulization times for IIM, CM, and EIM were 38.9,
      14.3, and 17.7 min, respectively, and nebulization time for the 3 modes
      significantly differed (P < .001). The inhaled drug mass for the 3 modes with the
      adult lung model was similar to that with the pediatric lung model (7.39 +/- 0.76
      vs. 6.27 +/- 0.69%, P = .77). CONCLUSIONS: Aerosol drug delivery with a jet
      nebulizer placed proximal to the ventilator was not dependent on nebulization
      mode during simulated pediatric and adult conventional mechanical ventilation.
      Use of expiratory intermittent mode and continuous nebulization should be
      considered to reduce treatment time.

PMID- 24865423
TI  - Pulmonary tuberculosis combined with hepatic tuberculosis: a case report and
      literature review.
AB  - BACKGROUND AND AIMS: Tuberculosis, a chronic infectious disease caused by
      Mycobacterium tuberculosis, may invade all organs but mainly affect lungs. Most
      hepatic tuberculosis could be a part of systemic miliary tuberculosis. METHODS:
      We reported a case of pulmonary tuberculosis combined with hepatic tuberculosis
      and reviewed the relevant literature. RESULTS: A 40-year-old Chinese male with
      fatigue for half a year and cough as well as night sweat for 2 months was
      admitted to our hospital. The chest computed tomography (CT) showed multiple
      nodules combined with bronchial stenosis and lymphadenectasis in the mediastina
      at the right hilum of lung. The epigastrium CT showed lumps in the liver and
      retroperitoneal lymphadenectasis in the peritoneal cavity. The abdominal color
      Doppler ultrasound revealed lumps in the liver. The lung and liver puncture
      biopsy revealed granulomatous lesions, chronic inflammatory changes in the strip
      like fibrous tissues and plenty of caseification, all of which suggest the
      diagnosis of tuberculosis. CONCLUSION: Hepatic tuberculosis is usually associated
      with atypical clinical manifestations. Imageological examination combined with
      imaging-guided fine needle aspiration biopsy may be the best method for the
      confirmed diagnosis.

PMID- 24865424
TI  - Lineage-specific splicing of a brain-enriched alternative exon promotes
      glioblastoma progression.
AB  - Tissue-specific alternative splicing is critical for the emergence of tissue
      identity during development, yet the role of this process in malignant
      transformation is undefined. Tissue-specific splicing involves evolutionarily
      conserved, alternative exons that represent only a minority of the total
      alternative exons identified. Many of these conserved exons have functional
      features that influence signaling pathways to profound biological effect. Here,
      we determined that lineage-specific splicing of a brain-enriched cassette exon in
      the membrane-binding tumor suppressor annexin A7 (ANXA7) diminishes endosomal
      targeting of the EGFR oncoprotein, consequently enhancing EGFR signaling during
      brain tumor progression. ANXA7 exon splicing was mediated by the
      ribonucleoprotein PTBP1, which is normally repressed during neuronal development.
      PTBP1 was highly expressed in glioblastomas due to loss of a brain-enriched
      microRNA (miR-124) and to PTBP1 amplification. The alternative ANXA7 splicing
      trait was present in precursor cells, suggesting that glioblastoma cells inherit
      the trait from a potential tumor-initiating ancestor and that these cells exploit
      this trait through accumulation of mutations that enhance EGFR signaling. Our
      data illustrate that lineage-specific splicing of a tissue-regulated alternative
      exon in a constituent of an oncogenic pathway eliminates tumor suppressor
      functions and promotes glioblastoma progression. This paradigm may offer a
      general model as to how tissue-specific regulatory mechanisms can reprogram
      normal developmental processes into oncogenic ones. 

PMID- 24865425
TI  - WNT5A enhances resistance of melanoma cells to targeted BRAF inhibitors.
AB  - About half of all melanomas harbor a mutation that results in a constitutively
      active BRAF kinase mutant (BRAF(V600E/K)) that can be selectively inhibited by
      targeted BRAF inhibitors (BRAFis). While patients treated with BRAFis initially
      exhibit measurable clinical improvement, the majority of patients eventually
      develop drug resistance and relapse. Here, we observed marked elevation of WNT5A
      in a subset of tumors from patients exhibiting disease progression on BRAFi
      therapy. WNT5A transcript and protein were also elevated in BRAFi-resistant
      melanoma cell lines generated by long-term in vitro treatment with BRAFi. RNAi
      mediated reduction of endogenous WNT5A in melanoma decreased cell growth,
      increased apoptosis in response to BRAFi challenge, and decreased the activity of
      prosurvival AKT signaling. Conversely, overexpression of WNT5A promoted melanoma
      growth, tumorigenesis, and activation of AKT signaling. Similarly to WNT5A
      knockdown, knockdown of the WNT receptors FZD7 and RYK inhibited growth,
      sensitized melanoma cells to BRAFi, and reduced AKT activation. Together, these
      findings suggest that chronic BRAF inhibition elevates WNT5A expression, which
      promotes AKT signaling through FZD7 and RYK, leading to increased growth and
      therapeutic resistance. Furthermore, increased WNT5A expression in BRAFi
      resistant melanomas correlates with a specific transcriptional signature, which
      identifies potential therapeutic targets to reduce clinical BRAFi resistance.

PMID- 24865427
TI  - Aldehyde dehydrogenase 1 defines and protects a nigrostriatal dopaminergic neuron
      subpopulation.
AB  - Subpopulations of dopaminergic (DA) neurons within the substantia nigra pars
      compacta (SNpc) display a differential vulnerability to loss in Parkinson's
      disease (PD); however, it is not clear why these subsets are preferentially
      selected in PD-associated neurodegeneration. In rodent SNpc, DA neurons can be
      divided into two subpopulations based on the expression of aldehyde dehydrogenase
      1 (ALDH1A1). Here, we have shown that, in alpha-synuclein transgenic mice, a
      murine model of PD-related disease, DA neurodegeneration occurs mainly in a
      dorsomedial ALDH1A1-negative subpopulation that is also prone to cytotoxic
      aggregation of alpha-synuclein. Notably, the topographic ALDH1A1 pattern observed
      in alpha-synuclein transgenic mice was conserved in human SNpc. Postmortem
      evaluation of brains of patients with PD revealed a severe reduction of ALDH1A1
      expression and neurodegeneration in the ventral ALDH1A1-positive DA
      subpopulations. ALDH1A1 expression was also suppressed in alpha-synuclein
      transgenic mice. Deletion of Aldh1a1 exacerbated alpha-synuclein-mediated DA
      neurodegeneration and alpha-synuclein aggregation, whereas Aldh1a1-null and
      control DA neurons were comparably susceptible to 1-methyl-4-phenylpyridinium-,
      glutamate-, or camptothecin-induced cell death. ALDH1A1 overexpression appeared
      to preferentially protect against alpha-synuclein-mediated DA neurodegeneration
      but did not rescue alpha-synuclein-induced loss of cortical neurons. Together,
      our findings suggest that ALDH1A1 protects subpopulations of SNpc DA neurons by
      preventing the accumulation of dopamine aldehyde intermediates and formation of
      cytotoxic alpha-synuclein oligomers. 

PMID- 24865428
TI  - Four individually druggable MET hotspots mediate HGF-driven tumor progression.
AB  - Activation of MET by HGF plays a key role in tumor progression. Using a recently
      developed llama platform that generates human-like immunoglobulins, we selected
      68 different antibodies that compete with HGF for binding to MET. HGF-competing
      antibodies recognized 4 distinct hotspots localized in different MET domains. We
      identified 1 hotspot that coincides with the known HGF beta chain binding site on
      blades 2-3 of the SEMA domain beta-propeller. We determined that a second and a
      third hotspot lie within blade 5 of the SEMA domain and IPT domains 2-3, both of
      which are thought to bind to HGF alpha chain. Characterization of the fourth
      hotspot revealed a region across the PSI-IPT 1 domains not previously associated
      with HGF binding. Individual or combined targeting of these hotspots effectively
      interrupted HGF/MET signaling in multiple cell-based biochemical and biological
      assays. Selected antibodies directed against SEMA blades 2-3 and the PSI-IPT 1
      region inhibited brain invasion and prolonged survival in a glioblastoma
      multiforme model, prevented metastatic disease following neoadjuvant therapy in a
      triple-negative mammary carcinoma model, and suppressed cancer cell dissemination
      to the liver in a KRAS-mutant metastatic colorectal cancer model. These results
      identify multiple regions of MET responsible for HGF-mediated tumor progression,
      unraveling the complexity of HGF-MET interaction, and provide selective molecular
      tools for targeting MET activity in cancer. 

PMID- 24865426
TI  - Monoamine oxidase A mediates prostate tumorigenesis and cancer metastasis.
AB  - Tumors from patients with high-grade aggressive prostate cancer (PCa) exhibit
      increased expression of monoamine oxidase A (MAOA), a mitochondrial enzyme that
      degrades monoamine neurotransmitters and dietary amines. Despite the association
      between MAOA and aggressive PCa, it is unclear how MAOA promotes PCa progression.
      Here, we found that MAOA functions to induce epithelial-to-mesenchymal transition
      (EMT) and stabilize the transcription factor HIF1alpha, which mediates hypoxia
      through an elevation of ROS, thus enhancing growth, invasiveness, and metastasis
      of PCa cells. Knockdown and overexpression of MAOA in human PCa cell lines
      indicated that MAOA induces EMT through activation of VEGF and its coreceptor
      neuropilin-1. MAOA-dependent activation of neuropilin-1 promoted AKT/FOXO1/TWIST1
      signaling, allowing FOXO1 binding at the TWIST1 promoter. Importantly, the MAOA
      dependent HIF1alpha/VEGF-A/FOXO1/TWIST1 pathway was activated in high-grade PCa
      specimens, and knockdown of MAOA reduced or even eliminated prostate tumor growth
      and metastasis in PCa xenograft mouse models. Pharmacological inhibition of MAOA
      activity also reduced PCa xenograft growth in mice. Moreover, high MAOA
      expression in PCa tissues correlated with worse clinical outcomes in PCa
      patients. These findings collectively characterize the contribution of MAOA in
      PCa pathogenesis and suggest that MAOA has potential as a therapeutic target in
      PCa. 

PMID- 24865434
TI  - Advocating for health equity policy: reflections and opportunities for
      collaborative engagement.

PMID- 24865433
TI  - Corpulence is the crucial factor: association of testosterone and/or obesity with
      prostate cancer stage.
AB  - OBJECTIVES: To evaluate whether low testosterone levels or obesity, or both, are
      directly associated with tumor stage/grade in patients with clinically localized
      prostate cancer. METHODS: Preoperative androgen serum levels (total and free
      testosterone), sex hormone-binding globulin, body mass index and waist
      circumference were assessed in 510 consecutive European Caucasian men treated
      with radical prostatectomy. Hormone levels and body mass index/waist
      circumference were correlated with patient- and tumor-specific characteristics
      using multivariable logistic regression analysis. RESULTS: Even though we
      confirmed an inverse correlation between bodyweight and testosterone levels, only
      overweight - but not low testosterone - was associated with advanced disease and
      poor differentiation of prostate cancer. Using multivariate analyses, both body
      mass index >=30 kg/m(2) and waist circumference >110 cm were associated with high
      grade disease (Gleason score >=8). A waist circumference >110 cm also correlated
      significantly with lymph node metastasis. CONCLUSIONS: This is the first study
      showing that obesity, but not low serum testosterone levels, is significantly
      associated with high grade and metastatic disease in men diagnosed with
      clinically localized prostate cancer. The present findings suggest that low
      androgen levels at diagnosis, which used to be held responsible for the
      development of aggressive prostate cancer, is only an epiphenomenon of obesity
      rather than the cause of prostate cancer development and/or progression.

PMID- 24865435
TI  - Occupational exposures and health outcomes among Latina hotel cleaners.
AB  - The poor working conditions of Latina hotel cleaners render them particularly
      vulnerable to elevated occupational hazards that lead to adverse health outcomes.
      This article presents a comprehensive review of occupational risks (including
      physical, chemical, biological, and psychosocial risk factors) and health
      outcomes (including musculoskeletal disorders, respiratory diseases,
      dermatological diseases and allergies, and psychological disorders) for Latina
      hotel cleaners, within their unique sociocultural contexts. Preventive
      interventions for improving Latina hotel cleaners' work and health conditions are
      recommended.

PMID- 24865429
TI  - Splicing regulator SLU7 is essential for maintaining liver homeostasis.
AB  - A precise equilibrium between cellular differentiation and proliferation is
      fundamental for tissue homeostasis. Maintaining this balance is particularly
      important for the liver, a highly differentiated organ with systemic metabolic
      functions that is endowed with unparalleled regenerative potential.
      Carcinogenesis in the liver develops as the result of hepatocellular de
      differentiation and uncontrolled proliferation. Here, we identified SLU7, which
      encodes a pre-mRNA splicing regulator that is inhibited in hepatocarcinoma, as a
      pivotal gene for hepatocellular homeostasis. SLU7 knockdown in human liver cells
      and mouse liver resulted in profound changes in pre-mRNA splicing and gene
      expression, leading to impaired glucose and lipid metabolism, refractoriness to
      key metabolic hormones, and reversion to a fetal-like gene expression pattern.
      Additionally, loss of SLU7 also increased hepatocellular proliferation and
      induced a switch to a tumor-like glycolytic phenotype. Slu7 governed the splicing
      and/or expression of multiple genes essential for hepatocellular differentiation,
      including serine/arginine-rich splicing factor 3 (Srsf3) and hepatocyte nuclear
      factor 4alpha (Hnf4alpha), and was critical for cAMP-regulated gene
      transcription. Together, out data indicate that SLU7 is central regulator of
      hepatocyte identity and quiescence. 

PMID- 24865431
TI  - beta2-Adrenergic agonists augment air pollution-induced IL-6 release and
      thrombosis.
AB  - Acute exposure to particulate matter (PM) air pollution causes thrombotic
      cardiovascular events, leading to increased mortality rates; however, the link
      between PM and cardiovascular dysfunction is not completely understood. We have
      previously shown that the release of IL-6 from alveolar macrophages is required
      for a prothrombotic state and acceleration of thrombosis following exposure to
      PM. Here, we determined that PM exposure results in the systemic release of
      catecholamines, which engage the beta2-adrenergic receptor (beta2AR) on murine
      alveolar macrophages and augment the release of IL-6. In mice, beta2AR signaling
      promoted the development of a prothrombotic state that was sufficient to
      accelerate arterial thrombosis. In primary human alveolar macrophages,
      administration of a beta2AR agonist augmented IL-6 release, while the addition of
      a beta blocker inhibited PM-induced IL-6 release. Genetic loss or pharmacologic
      inhibition of the beta2AR on murine alveolar macrophages attenuated PM-induced IL
      6 release and prothrombotic state. Furthermore, exogenous beta2AR agonist therapy
      further augmented these responses in alveolar macrophages through generation of
      mitochondrial ROS and subsequent increase of adenylyl cyclase activity. Together,
      these results link the activation of the sympathetic nervous system by beta2AR
      signaling with metabolism, lung inflammation, and an enhanced susceptibility to
      thrombotic cardiovascular events. 

PMID- 24865436
TI  - Latinas with elevated fasting plasma glucose: an analysis using NHANES 2009-2010
      data.
AB  - For Latinas with fasting plasma glucose (FPG) levels in the prediabetes and
      diabetes ranges, early detection can support steps to optimize their health. Data
      collected in 2009-2010 indicate that 36.7% of Latinas in the United States had
      elevated FPG levels. Latinas with elevated FPG who were unaware of their diabetes
      status were significantly less likely than non-Hispanic White and non-Hispanic
      Black women to have seen a health care provider in the past year (75.8%, 92.9%,
      and 90.2%, respectively; p = .018). With almost 1 million Latinas in the United
      States with elevated FPG unaware of their diabetes risk, and less likely than
      other at-risk women to see health care providers, there is an urgent need to
      establish alternate sites of opportunity for their diabetes screening. 

PMID- 24865438
TI  - Validation of a Spanish version of the practice environment scale of the nursing
      work index in the Colombian context.
AB  - The literature supports that organizations that create working conditions with
      positive practice environments improve nurses' job satisfaction and reduce
      turnover in hospital settings (Havens & Johnston, 2004; International Council of
      Nurses [ICN], 2007). Positive practice environments promote quality nursing care
      and better patient outcomes. However, in South America, there are no instruments
      to measure the nursing practice environment in a hospital setting. The purpose of
      this research was to examine the validity and reliability of a Spanish
      translation of the Practice Environment Scale of the Nursing Work Index (PES-NWI;
      Lake, 2002) in the Colombian clinical context. An instrument validation study
      using expert panel review, content validity indexing techniques, and a factor
      analysis of survey responses from 144 nurses was used. The scale-level content
      validity evaluation achieved high levels of acceptability, with values above
      0.90. Construct validity results suggest that the instrument consists of 5
      factors as prescribed by original instrument. The overall internal consistency
      value was a Cronbach's alpha level of 0.89. This is the first instrument to
      measure the work environment of nursing practice in South America, now validated
      in the Colombian context.

PMID- 24865430
TI  - Flow-dependent epigenetic DNA methylation regulates endothelial gene expression
      and atherosclerosis.
AB  - In atherosclerosis, plaques preferentially develop in arterial regions of
      disturbed blood flow (d-flow), which alters endothelial gene expression and
      function. Here, we determined that d-flow regulates genome-wide DNA methylation
      patterns in a DNA methyltransferase-dependent (DNMT-dependent) manner. Induction
      of d-flow by partial carotid ligation surgery in a murine model induced DNMT1 in
      arterial endothelium. In cultured endothelial cells, DNMT1 was enhanced by
      oscillatory shear stress (OS), and reduction of DNMT with either the inhibitor 5
      aza-2'-deoxycytidine (5Aza) or siRNA markedly reduced OS-induced endothelial
      inflammation. Moreover, administration of 5Aza reduced lesion formation in 2
      mouse models of atherosclerosis. Using both reduced representation bisulfite
      sequencing (RRBS) and microarray, we determined that d-flow in the carotid artery
      resulted in hypermethylation within the promoters of 11 mechanosensitive genes
      and that 5Aza treatment restored normal methylation patterns. Of the identified
      genes, HoxA5 and Klf3 encode transcription factors that contain cAMP response
      elements, suggesting that the methylation status of these loci could serve as a
      mechanosensitive master switch in gene expression. Together, our results
      demonstrate that d-flow controls epigenomic DNA methylation patterns in a DNMT
      dependent manner, which in turn alters endothelial gene expression and induces
      atherosclerosis. 

PMID- 24865437
TI  - Acceptability of the human papillomavirus vaccine among diverse Hispanic mothers
      and grandmothers.
AB  - The human papillomavirus (HPV) vaccine has the potential to reduce rates of
      cervical cancer and other HPV-related morbidity among Hispanic women who are
      disproportionately affected by this disease. Understanding the barriers faced by
      this population is an important public health goal. In this qualitative pilot
      study, 17 mothers and grandmothers of adolescent girls from diverse Hispanic
      backgrounds in a large northeastern city in the United States were interviewed to
      examine attitudes regarding vaccine acceptability. The findings reveal that
      negative media, concerns about sexuality, side effects, and efficacy may impact
      vaccine uptake and completion. Of the 4 participants whose daughters had received
      the vaccine, only 1 had completed the full series, which may speak to the trend
      of lower series completion among Hispanics. This pilot data could inform
      important considerations when designing longitudinal research that may provide
      some necessary insights into the factors that facilitate or impede HPV vaccine
      completion among U.S. Hispanics. 

PMID- 24865439
TI  - Using the PRECEDE-PROCEED model to assess dietary needs in the Hispanic
      population in northeastern Pennsylvania.
AB  - Research shows that as Hispanic immigrants spend more time in the United States
      and/or become more assimilated to the U.S. culture their diet begins to mimic
      that of a Western diet. A dietary needs assessment was conducted in the target
      population of low income, first-generation Hispanics in the greater Scranton, PA,
      area to identify nutrition problems and inform culturally appropriate nutrition
      intervention development. The PRECEDE-PROCEED model was used to guide the
      assessment. Interviews with key informants and a focus group as well as
      demographic and dietary-related questionnaires were completed with the target
      population to identify health and nutrition needs in the community and factors
      regarding dietary behaviors. Behavioral and environmental objectives were
      developed and led to a culturally tailored nutrition intervention.

PMID- 24865440
TI  - Altered structural covariance of the striatum in functional dyspepsia patients.
AB  - BACKGROUND: Functional dyspepsia (FD) is thought to be involved in dysregulation
      within the brain-gut axis. Recently, altered striatum activation has been
      reported in patients with FD. However, the gray matter (GM) volumes in the
      striatum and structural covariance patterns of this area are rarely explored. The
      purpose of this study was to examine the GM volumes and structural covariance
      patterns of the striatum between FD patients and healthy controls (HCs). METHODS:
      T1-weighted magnetic resonance images were obtained from 44 FD patients and 39
      HCs. Voxel-based morphometry (VBM) analysis was adopted to examine the GM volumes
      in the two groups. The caudate- or putamen-related regions identified from VBM
      analysis were then used as seeds to map the whole brain voxel-wise structural
      covariance patterns. Finally, a correlation analysis was used to investigate the
      effects of FD symptoms on the striatum. KEY RESULTS: The results showed increased
      GM volumes in the bilateral putamen and right caudate. Compared with the
      structural covariance patterns of the HCs, the FD-related differences were mainly
      located in the amygdala, hippocampus/parahippocampus (HIPP/paraHIPP), thalamus,
      lingual gyrus, and cerebellum. And significant positive correlations were found
      between the volumes in the striatum and the FD duration in the patients.
      CONCLUSIONS & INFERENCES: These findings provided preliminary evidence for GM
      changes in the striatum and different structural covariance patterns in patients
      with FD. The current results might expand our understanding of the
      pathophysiology of FD.

PMID- 24865441
TI  - Psychological morbidity associated with ovarian cancer screening: results from
      more than 23,000 women in the randomised trial of ovarian cancer screening
      (UKCTOCS).
AB  - OBJECTIVE: To examine the psychological sequelae associated with abnormal
      screening in the United Kingdom Collaborative Trial of Ovarian Cancer Screening
      (UKCTOCS). DESIGN: Prospective, longitudinal randomised control trial. SETTING:
      Sixteen UKCTOCS centres. SAMPLE: Women aged 50-70 years randomised to annual
      multimodal screening, ultrasound screening or control groups. METHODS: Two groups
      were followed for 7 years: (1) a random sample (n = 1339), taken from all three
      study groups; and (2) an events sample (n = 22,035) of women with abnormal
      screens resulting in the need for repeat testing of either low or higher level
      intensity. MAIN OUTCOME MEASURES: Patient-reported measures of anxiety (scores
      ranging from 20 to 80) and psychological morbidity. RESULTS: In the random sample
      the mean difference between anxiety scores after a repeat screening and those
      following an annual screening was 0.4 (95% CI -0.46, 1.27), and in the events
      sample it was 0.37 (95% CI 0.23, 0.51). The risk of psychological morbidity was
      only increased in the event sample for women requiring higher level repeat
      screening (OR 1.28; 95% CI 1.18, 1.39). The risk of psychological morbidity in
      women with ovarian cancer was higher at both 6 weeks (OR 16.2; 95% CI 9.19,
      28.54) and 6 months (OR 3.32; 95% CI 1.91, 5.77) following surgery. CONCLUSIONS:
      Screening does not appear to raise anxiety but psychological morbidity is
      elevated by more intense repeat testing following abnormal annual screens, and in
      women after surgical treatment for ovarian cancer.

PMID- 24865444
TI  - Utility of echocardiography in identifying right ventricular extension of Wilm's
      tumor.
AB  - We present a rare case of a child with a Wilm's tumor with an intravascular tumor
      thrombus extending from the inferior vena cava to the right ventricle via the
      tricuspid valve. Rapid tumor progression resulted in life-threatening clinical
      deterioration. Radiologic and cardiac imaging demonstrated the extent of the
      intravascular extension of her tumor-thrombus. Emergency neo-adjuvant
      chemotherapy resulted in rapid clinical improvement, so that complete surgical
      excision was possible. Following multimodality therapy, the child is now in
      remission. (c) 2014 Wiley Periodicals, Inc. J Clin Ultrasound 43:262-264, 2015.

PMID- 24865442
TI  - Differential expression of miRNAs in colon cancer between African and Caucasian
      Americans: implications for cancer racial health disparities.
AB  - Colorectal cancer (CRC) incidence and mortality are higher in African Americans
      (AAs) than in Caucasian Americans (CAs) and microRNAs (miRNAs) have been found to
      be dysregulated in colonic and other neoplasias. The aim of this exploratory
      study was to identify candidate miRNAs that could contribute to potential
      biological differences between AA and CA colon cancers. Total RNA was isolated
      from tumor and paired adjacent normal colon tissue from 30 AA and 31 CA colon
      cancer patients archived at Stony Brook University (SBU) and Washington
      University (WU)-St. Louis Medical Center. miRNA profiles were determined by
      probing human genome-wide miRNA arrays with RNA isolated from each sample. Using
      repeated measures analysis of variance (RANOVA), miRNAs were selected that
      exhibited significant (p<0.05) interactions between race and tumor or significant
      (fold change >1.5, p<0.05) main effects of race and/or tumor. Quantitative
      polymerase chain reaction (q-PCR) was used to confirm miRNAs identified by
      microarray analysis. Candidate miRNA targets were analyzed using
      immunohistochemistry. RANOVA results indicated that miR-182, miR152, miR-204, miR
      222 and miR-202 exhibited significant race and tumor main effects. Of these
      miRNAs, q-PCR analysis confirmed that miR-182 was upregulated in AA vs. CA tumors
      and exhibited significant race:tumor interaction. Immunohistochemical analysis
      revealed that the levels of FOXO1 and FOXO3A, two potential miR-182 targets, are
      reduced in AA tumors. miRNAs may play a role in the differences between AA and CA
      colon cancer. Specifically, differences in miRNA expression levels of miR-182 may
      contribute to decreased survival in AA colon cancer patients.

PMID- 24865445
TI  - Ecological factors predictive of wild spider monkey (Ateles belzebuth) foraging
      decisions in Yasuni, Ecuador.
AB  - Because fruiting trees are uncommon in tropical forests, frugivorous primates
      experience selective pressure to incorporate knowledge of where to find feeding
      trees, what to expect when they arrive there, and when they can return after
      depleting a tree. I investigated these abilities in wild spider monkeys (Ateles
      belzebuth) in Yasuni, Ecuador, by analyzing the characteristics of feeding trees
      that drive foraging decisions. Foraging data were derived from four 2-week
      follows of focal adult females, conducted between May and December 1999, during
      which I measured and mapped all trees in which the focal subject fed, feeding
      bout duration, and the number of conspecifics feeding simultaneously with the
      focal. Taking into account the order in which feeding trees were visited across
      each follow, I analyzed each foraging decision from the second week of a follow,
      treating all previously visited trees as options for visits. I scored each option
      tree in terms of nine ecological variables, including the distance from the
      decision to each location tree, DBH, recent feeding time and mean feeding times
      for the focal and other monkeys present, and the interval in hours between the
      foraging decision and the most recent visit to each option tree. I then examined
      the predictive strength of the model using logistic regression analysis,
      comparing characteristics of selected trees to those not selected. The overall
      model successfully predicted trees selected by focal monkeys (r(2)  = 0.27).
      Monkeys preferentially moved to nearby, large canopy trees, in which previous
      feeding success was high, and which were visited after an interval of 3.5 days.
      Interval mattered most for medium and large trees, but did not predict selection
      for trees <10 cm DBH. Despite the large home range and large numbers of trees,
      Yasuni spider monkeys appeared to integrate spatial, value, and temporal
      information when deciding where to feed.

PMID- 24865446
TI  - Sumatriptan (all routes of administration) for acute migraine attacks in adults -
      overview of Cochrane reviews.
AB  - BACKGROUND: Migraine is a highly disabling condition for the individual and also
      has wide-reaching implications for society, healthcare services, and the economy.
      Sumatriptan is an abortive medication for migraine attacks, belonging to the
      triptan family. It is available for administration by four different routes:
      oral, subcutaneous, intranasal, and rectal. OBJECTIVES: To summarise evidence
      from four Cochrane intervention reviews on the efficacy and tolerability of
      sumatriptan in the treatment of acute migraine attacks in adults by four routes
      of administration (oral, subcutaneous, intranasal, and rectal) compared with both
      placebo and active comparators. METHODS: The included reviews were written by the
      authors of this overview; no additional searching was carried out. All included
      reviews were conducted according to a standard protocol and reported a standard
      set of outcomes. From each individual review we extracted results for pain relief
      at different levels, and adverse events. No additional statistical comparison was
      undertaken as part of the overview. We focused on the most important findings for
      doses and routes licensed in North America or Europe (oral 25 mg, 50 mg, 100 mg;
      subcutaneous 4 mg, 6 mg; intranasal 5 mg, 10 mg, 20 mg; rectal 25 mg). MAIN
      RESULTS: Included reviews provided data for 18 different dose and route of
      administration combinations in 52,236 participants. Data for the primary outcomes
      sought were generally well reported, and involved adequate numbers of
      participants to give confidence in the results, except for the rectal route of
      administration, where numbers were low.Subcutaneous administration was the most
      effective, with pain reduced from moderate or severe to none by two hours in
      almost 6 in 10 people (59%) taking 6 mg sumatriptan, compared with approximately
      1 in 7 (15%) taking placebo; the number needed to treat (NNT) was 2.3 (95%
      confidence interval 2.1 to 2.4) with 2522 participants in the analysis. The most
      commonly used doses of oral, rectal, and intranasal sumatriptan also provided
      clinically useful pain relief, with the oral 50 mg dose providing complete relief
      of pain in almost 3 in 10 people (28%) compared with about 1 in 10 (11%) after
      placebo (NNT 6.1 (5.5 to 6.9) in 6447 participants). Subcutaneous administration
      provided more rapid pain relief than the other routes. Taking medication early,
      when pain was mild, was more effective than waiting until the pain was moderate
      or severe.The most effective dose of sumatriptan for each route of administration
      for the outcome of headache relief (pain reduced from moderate or severe to none
      or mild) at two hours was oral 100 mg (NNT 3.5 (3.2 to 3.7) in 7811
      participants), subcutaneous 6 mg (NNT 2.1 (2.0 to 2.2) in 2738 participants),
      intranasal 20 mg (NNT 3.5 (3.1 to 4.1) in 2020 participants), and rectal 25 mg
      (NNT 2.4 (1.9 to 3.4) in 240 participants).Adverse events were generally of mild
      or moderate severity, of short duration, and more common with subcutaneously
      administered sumatriptan and higher doses of oral and intranasal sumatriptan than
      with other dose and route combinations. AUTHORS' CONCLUSIONS: Sumatriptan is an
      effective abortive treatment for acute migraine attacks, but is associated with
      increased adverse events relative to placebo. The route of administration
      influences efficacy, particularly within the first hour after administration.
      Subcutaneous sumatriptan shows the greatest efficacy in terms of pain relief, but
      at the expense of relatively high levels of adverse events, and with a high
      financial cost compared with other routes. Information about the relative
      efficacy of the different routes of administration for different outcomes should
      help to inform decisions about the suitability of sumatriptan as a migraine
      treatment, as well as about the most appropriate way to administer the treatment
      for individual patients.

PMID- 24865447
TI  - In vivo T(2) relaxation time measurement with echo-time averaging.
AB  - The accuracy of metabolite concentrations measured using in vivo proton ((1) H)
      MRS is enhanced following correction for spin-spin (T2 ) relaxation effects. In
      addition, metabolite proton T2 relaxation times provide unique information
      regarding cellular environment and molecular mobility. Echo-time (TE) averaging
      (1) H MRS involves the collection and averaging of multiple TE steps, which
      greatly simplifies resulting spectra due to the attenuation of spin-coupled and
      macromolecule resonances. Given the simplified spectral appearance and inherent
      metabolite T2 relaxation information, the aim of the present proof-of-concept
      study was to develop a novel data processing scheme to estimate metabolite T2
      relaxation times from TE-averaged (1) H MRS data. Spectral simulations are used
      to validate the proposed TE-averaging methods for estimating methyl proton T2
      relaxation times for N-acetyl aspartate, total creatine, and choline-containing
      compounds. The utility of the technique and its reproducibility are demonstrated
      using data obtained in vivo from the posterior-occipital cortex of 10 healthy
      control subjects. Compared with standard methods, distinct advantages of this
      approach include built-in macromolecule resonance attenuation, in vivo T2
      estimates closer to reported values when maximum TE ~ T2 , and the potential for
      T2 calculation of metabolite resonances otherwise inseparable in standard (1) H
      MRS spectra recorded in vivo.

PMID- 24865449
TI  - Friend or foe? IgLON5 antibodies in a novel tauopathy with prominent sleep
      movement disorder, ataxia, and chorea.

PMID- 24865448
TI  - Anxiety in major depression and cerebrospinal fluid free gamma-aminobutyric acid.
AB  - BACKGROUND: Low gamma-aminobutyric acid (GABA) is implicated in both anxiety and
      depression pathophysiology. They are often comorbid, but most clinical studies
      have not examined these relationships separately. We investigated the
      relationship of cerebrospinal fluid (CSF) free GABA to the anxiety and depression
      components of a major depressive episode (MDE) and to monoamine systems. METHODS
      AND MATERIALS: Patients with a DSM-IV major depressive episode (N = 167: 130
      major depressive disorder; 37 bipolar disorder) and healthy volunteers (N = 38)
      had CSF free GABA measured by gas chromatography mass spectroscopy. Monoamine
      metabolites were assayed by high performance liquid chromatography.
      Symptomatology was assessed by Hamilton depression rating scale. RESULTS: Psychic
      anxiety severity increased with age and correlated with lower CSF free GABA,
      controlling for age. CSF free GABA declined with age but was not related to
      depression severity. Other monoamine metabolites correlated positively with CSF
      GABA but not with psychic anxiety or depression severity. CSF free GABA was lower
      in MDD compared with bipolar disorder and healthy volunteers. GABA levels did not
      differ based on a suicide attempt history in mood disorders. Recent exposure to
      benzodiazepines, but not alcohol or past alcoholism, was associated with a
      statistical trend for more severe anxiety and lower CSF GABA. CONCLUSIONS: Lower
      CSF GABA may explain increasing severity of psychic anxiety in major depression
      with increasing age. This relationship is not seen with monoamine metabolites,
      suggesting treatments targeting the GABAergic system should be evaluated in
      treatment-resistant anxious major depression and in older patients.

PMID- 24865451
TI  - Superhydrophilic and underwater superoleophobic poly(sulfobetaine methacrylate)
      grafted glass fiber filters for oil-water separation.
AB  - Oil-water separation is a major problem in industries such as oil production and
      wastewater treatment, where millions of gallons of oil-contaminated water are
      produced. Zwitterionic poly(sulfobetaine methacrylate) (pSBMA) is a
      superhydrophilic polymer due to its strong interaction with water via
      electrostatic interactions. By coating surfaces of filter media with such a
      superhydrophilic polymer, it is expected that one can effectively separate oil
      and water. In this work, pSBMA was grafted onto glass fiber surfaces using
      surface-initiated atom transfer radical polymerization (SI-ATRP). The in-air
      water contact angle of the pSBMA-treated glass was 8-15 degrees , as compared to
      31 degrees  for the control untreated glass, whereas the underwater-oil contact
      angle of the pSBMA-grafted glass was 162-169 degrees , as compared to 142 degrees
      for the control pristine glass, suggesting that the pSBMA-grafted glass slides
      are superhydrophilic and underwater superoleophobic. Such superhydrophilicity and
      underwater superoleophobicity were realized by modifying surface chemistry only,
      with no need to create rough surfaces. The pSBMA-grafted glass fiber filters
      demonstrated exceptional results at separating oil from water without even
      allowing miniscule amounts of visible oil to permeate through. 

PMID- 24865452
TI  - Controlled protein delivery from electrospun non-wovens: novel combination of
      protein crystals and a biodegradable release matrix.
AB  - Poly-epsilon-caprolactone (PCL) is an excellent polymer for electrospinning and
      matrix-controlled drug delivery combining optimal processability and good
      biocompatibility. Electrospinning of proteins has been shown to be challenging
      via the use of organic solvents, frequently resulting in protein unfolding or
      aggregation. Encapsulation of protein crystals represents an attractive but
      largely unexplored alternative to established protein encapsulation techniques
      because of increased thermodynamic stability and improved solvent resistance of
      the crystalline state. We herein explore the electrospinning of protein crystal
      suspensions and establish basic design principles for this novel type of protein
      delivery system. PCL was deployed as a matrix, and lysozyme was used as a
      crystallizing model protein. By rational combination of lysozyme crystals 0.7 or
      2.1 MUm in diameter and a PCL fiber diameter between 1.6 and 10 MUm, release
      within the first 24 h could be varied between approximately 10 and 100%. Lysozyme
      loading of PCL microfibers between 0.5 and 5% was achieved without affecting
      processability. While relative release was unaffected by loading percentage, the
      amount of lysozyme released could be tailored. PCL was blended with poly(ethylene
      glycol) and poly(lactic-co-glycolic acid) to further modify the release rate.
      Under optimized conditions, an almost constant lysozyme release over 11 weeks was
      achieved. 

PMID- 24865450
TI  - Individual and community level risk-factors for alcohol use disorder among
      conflict-affected persons in Georgia.
AB  - BACKGROUND: The evidence on alcohol use disorder among conflict-affected civilian
      populations remains extremely weak, despite a number of potential risk-factors.
      The aim of this study is to examine patterns of alcohol use disorder among
      conflict-affected persons in the Republic of Georgia. METHODS: A cross-sectional
      survey of 3600 randomly selected internally displaced persons (IDPs) and former
      IDPs. Two alcohol use disorder outcomes were measured: (i) having at least
      hazardous alcohol use (AUDIT score >= 8); (ii) episodic heavy drinking (consuming
      >60 grams of pure alcohol per drinking session at least once a week). Individual
      level demographic and socio-economic characteristics were also recorded,
      including mental disorders. Community level alcohol environment characteristics
      relating to alcohol availability, marketing and pricing were recorded in the
      respondents' communities and a factor analysis conducted to produce a summary
      alcohol environment factor score. Logistic regression analyses examined
      associations between individual and community level factors with the alcohol use
      disorder outcomes (among men only). RESULTS: Of the total sample, 71% of men and
      16% of women were current drinkers. Of the current drinkers (N = 1386), 28% of
      men and 1% of women were classified as having at least hazardous alcohol use; and
      12% of men and 2% of women as episodic heavy drinkers. Individual characteristics
      significantly associated with both outcomes were age and experiencing a serious
      injury, while cumulative trauma events and depression were also associated with
      having at least hazardous alcohol use. For the community level analysis, a one
      unit increase in the alcohol environment factor was associated with a 1.27 fold
      increase in episodic heavy drinking among men (no significant association with
      hazardous alcohol use). CONCLUSION: The findings suggest potential synergies for
      treatment responses for alcohol use disorder and depression among conflict
      affected populations in Georgia, as well as the need for stronger alcohol control
      policies in Georgia.

PMID- 24865453
TI  - Simultaneous determination of ethyl carbamate and 4-(5-)methylimidazole in yellow
      rice wine and soy sauce by gas chromatography with mass spectrometry.
AB  - We developed a new method, based on alkaline diatomite solid-phase extraction
      followed by gas chromatography with mass spectrometry, for the simultaneous
      determination of the toxic contaminants ethyl carbamate (EC) and 4-(5
      )methylimidazole (4-MEI) in yellow rice wine and soy sauce. The optimal
      extraction conditions were defined. With the application of alkaline diatomite
      solid-phase extraction, damage to the capillary column by organic acids was
      greatly reduced. With deuterated EC used as the internal standard, the linearity
      of the calibration curves for EC and 4-MEI was good with correlation coefficient
      above 0.99. In a spiked experiment with EC and 4-MEI in yellow rice wine and soy
      sauce, recovery of the added EC was 80.5-102.5% and that of 4-MEI was 78.3-92.8%.
      The limit of quantification and limit of detection for EC were 6.0 and 2.0
      MUg/kg, respectively, and for 4-MEI were 15.0 and 5.0 MUg/kg, respectively. The
      validation results demonstrate that the method is fast, simple, and selective,
      and therefore is suitable for simultaneously determining the presence of EC and 4
      MEI in fermented food. 

PMID- 24865457
TI  - Back to BaySICS: a user-friendly program for Bayesian Statistical Inference from
      Coalescent Simulations.
AB  - Inference of population demographic history has vastly improved in recent years
      due to a number of technological and theoretical advances including the use of
      ancient DNA. Approximate Bayesian computation (ABC) stands among the most
      promising methods due to its simple theoretical fundament and exceptional
      flexibility. However, limited availability of user-friendly programs that perform
      ABC analysis renders it difficult to implement, and hence programming skills are
      frequently required. In addition, there is limited availability of programs able
      to deal with heterochronous data. Here we present the software BaySICS: Bayesian
      Statistical Inference of Coalescent Simulations. BaySICS provides an integrated
      and user-friendly platform that performs ABC analyses by means of coalescent
      simulations from DNA sequence data. It estimates historical demographic
      population parameters and performs hypothesis testing by means of Bayes factors
      obtained from model comparisons. Although providing specific features that
      improve inference from datasets with heterochronous data, BaySICS also has
      several capabilities making it a suitable tool for analysing contemporary genetic
      datasets. Those capabilities include joint analysis of independent tables, a
      graphical interface and the implementation of Markov-chain Monte Carlo without
      likelihoods. 

PMID- 24865454
TI  - Structural studies of an anti-inflammatory lectin from Canavalia boliviana seeds
      in complex with dimannosides.
AB  - Plant lectins, especially those purified from species of the Leguminosae family,
      represent the best-studied group of carbohydrate-binding proteins. Lectins
      purified from seeds of the Diocleinae subtribe exhibit a high degree of sequence
      identity notwithstanding that they show very distinct biological activities. Two
      main factors have been related to this feature: variance in key residues
      influencing the carbohydrate-binding site geometry and differences in the pH
      dependent oligomeric state profile. In this work, we have isolated a lectin from
      Canavalia boliviana (Cbol) and solved its x-ray crystal structure in the unbound
      form and in complex with the carbohydrates Man(alpha1-3)Man(alpha1-O)Me,
      Man(alpha1-4)Man(alpha1-O)Me and 5-bromo-4-chloro-3-indolyl-alpha-D-mannose. We
      evaluated its oligomerization profile at different pH values using Small Angle X
      ray Scattering and compared it to that of Concanavalin A. Based on predicted pKa
      shifts of amino acids in the subunit interfaces we devised a model for the dimer
      tetramer equilibrium phenomena of these proteins. Additionally, we demonstrated
      Cbol anti-inflammatory properties and further characterized them using in vivo
      and in vitro models. 

PMID- 24865459
TI  - The impact of NHS resource allocation policy on health inequalities in England
      2001-11: longitudinal ecological study.
AB  - OBJECTIVE: To investigate whether the policy of increasing National Health
      Service funding to a greater extent in deprived areas in England compared with
      more affluent areas led to a reduction in geographical inequalities in mortality
      amenable to healthcare. DESIGN: Longitudinal ecological study. SETTING: 324 lower
      tier local authorities in England, classified by their baseline level of
      deprivation. INTERVENTION: Differential trends in NHS funds allocated to local
      areas resulting from the NHS resource allocation policy in England between 2001
      and 2011. MAIN OUTCOME MEASURE: Trends in mortality from causes considered
      amenable to healthcare in local authority areas in England. Using multivariate
      regression, we estimated the reduction in mortality that was associated with the
      allocation of additional NHS resources in these areas. RESULTS: Between 2001 and
      2011 the increase in NHS resources to deprived areas accounted for a reduction in
      the gap between deprived and affluent areas in male mortality amenable to
      healthcare of 35 deaths per 100,000 population (95% confidence interval 27 to 42)
      and female mortality of 16 deaths per 100,000 (10 to 21). This explained 85% of
      the total reduction of absolute inequality in mortality amenable to healthcare
      during this time. Each additional L10 m of resources allocated to deprived areas
      was associated with a reduction in 4 deaths in males per 100,000 (3.1 to 4.9) and
      1.8 deaths in females per 100,000 (1.1 to 2.4). The association between absolute
      increases in NHS resources and improvements in mortality amenable to healthcare
      in more affluent areas was not significant. CONCLUSION: Between 2001 and 2011,
      the NHS health inequalities policy of increasing the proportion of resources
      allocated to deprived areas compared with more affluent areas was associated with
      a reduction in absolute health inequalities from causes amenable to healthcare.
      Dropping this policy may widen inequalities.

PMID- 24865461
TI  - A comprehensive picture of the mutations associated with aromatic amino acid
      decarboxylase deficiency: from molecular mechanisms to therapy implications.
AB  - Dopa decarboxylase (DDC), or aromatic amino acid decarboxylase (AADC), is a
      pyridoxal 5'-phosphate enzyme responsible for the production of the
      neurotransmitters dopamine and serotonin. Deficit of this enzyme causes AADC
      deficiency, an inherited neurometabolic disorder. To date, 18 missense homozygous
      mutations have been identified through genetic screening in ~80 patients.
      However, little is known about the mechanism(s) by which mutations cause disease.
      Here we investigated the impact of these pathogenic mutations and of an
      artificial one on the conformation and the activity of wild-type DDC by a
      combined approach of bioinformatic, spectroscopic and kinetic analyses. All
      mutations reduce the kcat value, and, except the mutation R347Q, alter the
      tertiary structure, as revealed by an increased hydrophobic surface and a
      decreased near-UV circular dichroism signal. The integrated analysis of the
      structural and functional consequences of each mutation strongly suggests that
      the reason underlying the pathogenicity of the majority of disease-causing
      mutations is the incorrect apo-holo conversion. In fact, the most remarkable
      effects are seen upon mutation of residues His70, His72, Tyr79, Phe80, Pro81,
      Arg462 and Arg447 mapping to or directly interacting with loop1, a structural key
      element involved in the apo-holo switch. Instead, different mechanisms are
      responsible for the pathogenicity of R347Q, a mere catalytic mutation, and of
      L38P and A110Q mutations causing structural-functional defects. These are due to
      local perturbation transmitted to the active site, as predicted by molecular
      dynamic analyses. Overall, the results not only give comprehensive molecular
      insights into AADC deficiency, but also provide an experimental framework to
      suggest appropriate therapeutic treatments. 

PMID- 24865463
TI  - Pore-scale controls on calcite dissolution rates from flow-through laboratory and
      numerical experiments.
AB  - A combination of experimental, imaging, and modeling techniques were applied to
      investigate the pore-scale transport and surface reaction controls on calcite
      dissolution under elevated pCO2 conditions. The laboratory experiment consisted
      of the injection of a solution at 4 bar pCO2 into a capillary tube packed with
      crushed calcite. A high resolution pore-scale numerical model was used to
      simulate the experiment based on a computational domain consisting of reactive
      calcite, pore space, and the capillary wall constructed from volumetric X-ray
      microtomography images. Simulated pore-scale effluent concentrations were higher
      than those measured by a factor of 1.8, with the largest component of the
      discrepancy related to uncertainties in the reaction rate model and its
      parameters. However, part of the discrepancy was apparently due to mass transport
      limitations to reactive surfaces, which were most pronounced near the inlet where
      larger diffusive boundary layers formed around grains and in slow-flowing pore
      spaces that exchanged mass by diffusion with fast flow paths. Although minor, the
      difference between pore- and continuum-scale results due to transport controls
      was discernible with the highly accurate methods employed and is expected to be
      more significant where heterogeneity is greater, as in natural subsurface
      materials. 

PMID- 24865460
TI  - mTOR pathway is activated by PKA in adrenocortical cells and participates in vivo
      to apoptosis resistance in primary pigmented nodular adrenocortical disease
      (PPNAD).
AB  - Primary pigmented nodular adrenocortical disease (PPNAD) is associated with
      inactivating mutations of the PRKAR1A tumor suppressor gene that encodes the
      regulatory subunit R1alpha of the cAMP-dependent protein kinase (PKA). In human
      and mouse adrenocortical cells, these mutations lead to increased PKA activity,
      which results in increased resistance to apoptosis that contributes to the
      tumorigenic process. We used in vitro and in vivo models to investigate the
      possibility of a crosstalk between PKA and mammalian target of rapamycin (mTOR)
      pathways in adrenocortical cells and its possible involvement in apoptosis
      resistance. Impact of PKA signaling on activation of the mTOR pathway and
      apoptosis was measured in a mouse model of PPNAD (AdKO mice), in human and mouse
      adrenocortical cell lines in response to pharmacological inhibitors and in PPNAD
      tissues by immunohistochemistry. AdKO mice showed increased mTOR complex 1
      (mTORC1) pathway activity. Inhibition of mTORC1 by rapamycin restored sensitivity
      of adrenocortical cells to apoptosis in AdKO but not in wild-type mice. In both
      cell lines and mouse adrenals, rapid phosphorylation of mTORC1 targets including
      BAD proapoptotic protein was observed in response to PKA activation. Accordingly,
      BAD hyperphosphorylation, which inhibits its proapoptotic activity, was increased
      in both AdKO mouse adrenals and human PPNAD tissues. In conclusion, mTORC1
      pathway is activated by PKA signaling in human and mouse adrenocortical cells,
      leading to increased cell survival, which is correlated with BAD
      hyperphosphorylation. These alterations could be causative of tumor formation. 

PMID- 24865462
TI  - The prevalence and determinants of problem gambling in Australia: assessing the
      impact of interactive gambling and new technologies.
AB  - New technology is changing the nature of gambling with interactive modes of
      gambling becoming putatively associated with higher rates of problem gambling.
      This paper presents the first nationally representative data on the prevalence
      and correlates of problem gambling among Australian adults since 1999 and focuses
      on the impact of interactive gambling. A telephone survey of 15,006 adults was
      conducted. Of these, 2,010 gamblers (all interactive gamblers and a randomly
      selected subsample of those reporting land-based gambling in the past 12 months)
      also completed more detailed measures of problem gambling, substance use,
      psychological distress, and help-seeking. Problem gambling rates among
      interactive gamblers were 3 times higher than for noninteractive gamblers.
      However, problem and moderate risk gamblers were most likely to attribute
      problems to electronic gaming machines and land-based gambling, suggesting that
      although interactive forms of gambling are associated with substantial problems,
      interactive gamblers experience significant harms from land-based gambling. The
      findings demonstrate that problem gambling remains a significant public health
      issue that is changing in response to new technologies, and it is important to
      develop strategies that minimize harms among interactive gamblers.

PMID- 24865465
TI  - Live cell interactome of the human voltage dependent anion channel 3 (VDAC3)
      revealed in HeLa cells by affinity purification tag technique.
AB  - In higher eukaryotes three different VDAC genes encode three homologous proteins
      which do not show the same activity. VDAC1 and VDAC2 isoforms have been
      characterized while VDAC3 isoform is still elusive. To explore VDAC3 protein
      interactions, we have established a stable cell line expressing a fluorescent and
      dual-tagged construct. This clone expresses a stable amount of VDAC3. Live cell
      imaging shows that fluorescent VDAC3 localizes in the mitochondria. Proteins
      interacting with VDAC3 have been separated by tandem-affinity purification and 2
      D gel electrophoresis and identified by mass spectrometry. In the list of
      putative interacting proteins, there are cytosolic, mitochondrial, cytoskeletal
      and ER proteins. Coherent pathways like cell redox homeostasis, response to
      stress, formation/rearrangement of disulfide bonds, response to unfolded proteins
      or protein folding have been found to be related to clusters of proteins
      identified in this experiment. The list of associated proteins has been validated
      by immunoprecipitation experiments utilizing specific antibodies. Likely
      biological and pathological processes have been analyzed. Cytosolic proteins
      associated with VDAC3 include tubulins and cytoskeletal proteins, stress sensors,
      chaperones and proteasome components, redox-mediating enzymes such as protein
      disulphide isomerase. The overall picture points to a role for VDAC3 as mediator
      for the organization of protein complexes and regulator of the traffic of
      misfolded or non-folded proteins evoked from different stimuli. 

PMID- 24865467
TI  - Bacterial chemotaxis without gradient-sensing.
AB  - Chemotaxis models are based on spatial or temporal gradient measurements by
      individual organisms. The key contribution of Keller and Segel (J Theor Biol
      30:225-234, 1971a; J Theor Biol 30:235-248, 1971b) is showing that erratic
      measurements of individuals may result in an accurate chemotaxis phenomenon as a
      group. In this paper we provide another option to understand chemotactic behavior
      when individuals do not sense the gradient of chemical concentration by any
      means. We show that, if individuals increase their dispersal rate to find food
      when there is not enough food, an accurate chemotactic behavior may be obtained
      without sensing the gradient. Such a dispersal has been suggested by Cho and Kim
      (Bull Math Biol 75:845-870, 2013) and was called starvation driven diffusion.
      This model is surprisingly similar to the original Keller-Segel model. A
      comprehensive picture of traveling bands and fronts is provided. 

PMID- 24865466
TI  - Development of asthmatic response upon bronchial allergen challenge is associated
      with dynamic changes of interleukin-10-producing and interleukin-10-responding
      CD4+ T cells.
AB  - The role of adaptive immune system in regulation of asthmatic responses remains
      elusive. Here, we performed a comprehensive time-course analysis of mutual
      relationships between development of asthmatic response following allergen
      challenge and changes in several CD4+ T cell subsets which we characterized as
      either releasing interleukin-10 (CD4+CD25-CD127- and CD4+CD25+CD127+ T cells) or
      responding to IL-10 (CD4+ T cell subsets expressing CD210). Patients that
      developed asthmatic reaction were described as responders (R) whereas the others
      were named non-responders (NR). In R, in contrast to NR, at 6 h, we demonstrated
      significant expansion of CD4+CD25-CD127- T cells which was followed by drop to
      baseline values at 24 h. In contrast, in R, we observed decrease in numbers of
      CD4+CD25+CD127+ and CD4+CD25-CD127+ T cells at 24 h. Interestingly, at baseline,
      despite comparable IL-10 levels, R presented with lower levels of all CD4+ T cell
      subsets expressing CD210. In R, the numbers of CD4+CD210+ T cell subsets were
      further decreased following bronchial challenge which was paralleled by decrease
      in IL-10 serum levels. Altogether, our data suggest that dynamic interactions
      between IL-10-producing and IL-10-responding CD4+ T cells could contribute to
      pathogenesis of asthmatic responses in atopic individuals.

PMID- 24865468
TI  - Psoriasis causes significant economic burden to patients.
AB  - INTRODUCTION: Psoriasis results in expenses to patients from many cost sources.
      Psoriasis treatments may result in considerable time and traveling costs, yet
      many studies fail to account for these costs. The objective of this study was to
      evaluate the multidimensional economic burden of psoriasis to patients. METHODS:
      The study was based on 232 Finnish patients with psoriasis or psoriatic arthritis
      visiting a tertiary level dermatological clinic during a 1-year study period
      between October 1, 2009 and September 30, 2010. The data were based on a patient
      questionnaire, clinical data from the medical records and reimbursement data from
      the Finnish Social Insurance Institution. Item costs were based on true costs
      charged from the patients and all time cost estimates were based on the Human
      Capital Approach method. RESULTS: 199 patients with psoriasis and 33 with
      psoriatic arthritis were included in the study. Total costs were higher for
      patients receiving traditional systemic medications or phototherapy than those
      not receiving such treatment. Travel costs and travel time costs accounted for
      more than 60% of the costs of phototherapy. Skin care at home was time consuming
      and thus caused significant burden to patients. The majority of the visit costs
      arose from hospital visits and only a small proportion were attributed to
      visiting primary health care providers. CONCLUSION: Visit charges and other
      patient co-payments were estimated to play a minor role in the total cost of
      psoriasis incurred by patients, while travel costs and lost time comprised the
      majority of the costs, which should not be omitted in future studies regarding
      costs of treatments.

PMID- 24865469
TI  - Molecular dynamics study of segment peptides of Bax, Bim, and Mcl-1 BH3 domain of
      the apoptosis-regulating proteins bound to the anti-apoptotic Mcl-1 protein.
AB  - Mcl-1 has emerged as a potential therapeutic target in the treatment of several
      malignancies. Peptides representing BH3 region of pro-apoptotic proteins have
      been shown to bind the hydrophobic cleft of anti-apoptotic Mcl-1 and this segment
      is responsible for modulating the apoptotic pathways in living cells.
      Understanding the molecular basis of protein-peptide interaction is required to
      develop potent inhibitors specific for Mcl-1. Molecular dynamics simulations were
      performed for Mcl-1 in complex with three different BH3 peptides derived from Mcl
      1, Bax, and Bim. Accordingly, the calculated binding free energies using MM-PBSA
      method are obtained and comparison with the experimentally determined binding
      free energies is made. The interactions involving two conserved charged residues
      (Aspi, and Arg/Lysi-4) and three upstream conserved hydrophobic residues (Leui-5,
      Ile/Vali-2, and Glyi-1, respectively) of BH3 peptides play the important roles in
      the structural stability of the complexes. The calculated results exhibit that
      the interactions of Bim BH3 peptides to Mcl-1 is stronger than the complex with
      Bax 19BH3 peptides. The hydrophobic residues (position i - 9, i - 8 and i + 2) of
      BH3 peptides can be involved in their inhibitory specificity. The calculated
      results can be used for designing more effective MCL-1 inhibitors. 

PMID- 24865470
TI  - Creeping motion of self interstitial atom clusters in tungsten.
AB  - The formation and motion features of self interstitial atom (SIA) clusters in
      tungsten are studied by molecular dynamics (MD) simulations. The static
      calculations show that the SIA clusters are stable with binding energy over 2 eV.
      The SIA clusters exhibit a fast one dimensional (1D) motion along <111>. Through
      analysis of the change of relative distance between SIAs, we find that SIAs jump
      in small displacements we call creeping motion, which is a new collective
      diffusion process different from that of iron. The potential energy surface of
      SIAs implicates that the creeping motion is due to the strong interaction between
      SIAs. These imply that several diffusion mechanism for SIA clusters can operate
      in BCC metals and could help us explore deep insight into the performance of
      materials under irradiation. 

PMID- 24865471
TI  - Klippel-Feil syndrome and levo-looped transposition of the great arteries.
AB  - Klippel-Feil syndrome is a skeletal disorder characterised by low hairline and a
      short neck due to abnormal fusion of two or more cervical vertebrae. Although
      congenital heart and lung defects are infrequent, some abnormalities such as cor
      triatriatum, coarctation of the aorta, total anomalous pulmonary venous
      connection, or lung agenesis have been reported. The challenge of recognising
      Klippel-Feil syndrome lies in the fact that there is an association of this
      syndrome with other significant conditions such as skeletal, genitourinary,
      neurological, ear, and some cardiac defects. We report a Klippel-Feil syndrome
      type III 14-year-old patient with a levo-looped transposition of the great
      arteries. In addition, the patient had agenesis of the left upper-lung lobe. 

PMID- 24865472
TI  - The urban homeless: super-users of the emergency department.
AB  - In the United States, patient usage of costly emergency departments (EDs) has
      been portrayed as a major factor contributing to health care expenditures. The
      homeless are associated with ED frequent users, a population often blamed for
      inappropriate ED use. This study examined the characteristics and costs
      associated with homeless ED frequent users. A retrospective cross-sectional
      review of hospital records for ED visits in 2006 at an urban academic medical
      center was performed. Frequent users were defined as having greater than 4 ED
      visits in one year. Homeless status was determined by self-report and review by
      an interdisciplinary team. A total of 5440 (8.9%) ED visits were made by 542
      frequent users, 74 (13.7%) of whom were homeless and made 845 ED visits. Homeless
      frequent users had a median age of 47 years (39-56 interquartile range), were
      predominantly male (85.1%), and insured by Medicaid (59.5%). Most (44.2%) visits
      by homeless frequent users occurred between 1500-2259 hours and had an Emergency
      Severity Index of Level 3 (55.5%). Sixty-four percent of visits resulted in
      homeless patients being discharged back to the street; only 4.0% had a specific
      discharge plan addressing homelessness. Total charges and payments for all
      homeless frequent users were $4,812,615 and $802,600, respectively. The single
      top frequent user accrued charges of $482,928. ED frequent users are
      disproportionately homeless and their costs are significant. ED discharge
      planning should address the additional risks faced by homeless individuals. ED
      based interventions that specifically target the most expensive homeless frequent
      users may prove to be cost-effective.

PMID- 24865473
TI  - Enantioselective acylphosphonylation-dual Lewis acid-Lewis base activation of
      aldehyde and acylphosphonate.
AB  - Acetoxyphosphonates were obtained by a one-step procedure consisting of reaction
      of diethyl acetylphosphonate with prochiral aldehydes in the presence of a
      catalytic system comprising a chiral Lewis acid, an achiral Lewis base, and a
      Bronstedt base. Best results were obtained using a tridentate Schiff base
      aluminum(III) Lewis acidic complex, 1H-1,2,3-benzotriazole, and a tertiary amine
      such as DBU. The target compounds were in most cases obtained in high yields, but
      with moderate enantiomeric ratios (up to 78:22). 

PMID- 24865475
TI  - Endoscopic endonasal resection of large skull base schwannoma.
AB  - Schwannomas of the skull base can pose a surgical challenge due to their
      anatomical location. To date extensive craniofacial approaches have had to be
      used to access these lesions. We present a patient where an expanded endoscopic
      endonasal approach was used to address a large skull base schwannoma with good
      results. The approach confers significantly less morbidity and a substantially
      shorter hospital stay.

PMID- 24865474
TI  - Carboplatin-based combination chemotherapy for elderly patients with advanced
      bladder cancer.
AB  - BACKGROUND: We evaluated retrospectively the feasibility and effectiveness of
      carboplatin-based combination chemotherapy in elderly patients with advanced
      bladder cancer. METHODS: Forty-seven patients with advanced bladder cancer (33
      men and 14 women) and treated at our hospital between August 2004 and December
      2011 were enrolled. The average age was 77.1 years (range 70-86 years), the
      average creatinine clearance was 37.0 ml/min (range 14.5-113.0 ml/min), and the
      average follow-up period was 17.4 months (range 10-55 months). Twenty-nine
      patients (61.7 %) were unfit for cisplatin-based chemotherapy. There were 15
      recurrent cases after radical surgery and 32 inoperable cases. In this study, the
      first-line therapy was gemcitabine and carboplatin (GCarbo), with two courses as
      a set. The second-line therapy was GCarbo and docetaxel (GCarboD) if there was an
      insufficient response to the first-line therapy. RESULTS: Of the 47 patients who
      underwent GCarbo therapy, the response rate was 38.3 % (complete response plus
      partial response), with 5 and 13 patients exhibiting a complete response and a
      partial response, respectively. The average response duration was 15.7 months
      (range 2-42 months). The response rate of the nine patients who received GCarboD
      was 11.1 %, and the overall median survival was 15.0 months. Adverse events
      occurred in 30 patients (63.8 %) who underwent GCarbo therapy. Bone marrow
      suppression was observed in 30 patients (61.7 %), and digestive symptoms were
      observed in three patients (9.0 %). CONCLUSION: Our study demonstrates that
      GCarbo is a safe and effective combination chemotherapy in elderly patients with
      advanced bladder cancer. However, the GCarboD regimen appears to have limited
      effectiveness for nonresponders to GCarbo therapy.

PMID- 24865476
TI  - Imatinib mesylate stimulates low-density lipoprotein receptor-related protein 1
      mediated ERK phosphorylation in insulin-producing cells.
AB  - Low-density lipoprotein receptor-related protein 1 (LRP1) is an endocytic and
      multi-functional type I cell surface membrane protein, which is known to be
      phosphorylated by the activated platelet-derived growth factor receptor (PDGFR).
      The tyrosine kinase inhibitor imatinib, which inhibits PDGFR and c-Abl, and which
      has previously been reported to counteract beta-cell death and diabetes, has been
      suggested to reduce atherosclerosis by inhibiting PDGFR-induced LRP1
      phosphorylation. The aim of the present study was to study LRP1 function in beta
      cells and to what extent imatinib modulates LRP1 activity. LRP1 and c-Abl gene
      knockdown was performed by RNAi using rat INS-1 832/13 and human EndoC1-betaH1
      cells. LRP1 was also antagonized by treatment with the antagonist low-density
      lipoprotein receptor-related protein associated protein 1 (LRPAP1). We have used
      PDGF-BB, a PDGFR agonist, and apolipoprotein E (ApoE), an LRP1 agonist, to
      stimulate the activities of PDGFR and LRP1 respectively. Knockdown or inhibition
      of LRP1 resulted in increased hydrogen peroxide (H2O2)- or cytokine-induced cell
      death, and glucose-induced insulin release was lowered in LRP1-silenced cells.
      These results indicate that LRP1 function is necessary for beta-cell function and
      that LRP1 is adversely affected by challenges to beta-cell health. PDGF-BB, or
      the combination of PDGF-BB+ApoE, induced phosphorylation of extracellular-signal
      regulated kinase (ERK), Akt and LRP1. LRP1 silencing blocked this event. Imatinib
      blocked phosphorylation of LRP1 by PDGFR activation but induced phosphorylation
      of ERK. LRP1 silencing blocked imatinib-induced phosphorylation of ERK. Sunitinib
      also blocked LRP1 phosphorylation in response to PDGF-BB and induced
      phosphorylation of ERK, but this latter event was not affected by LRP1 knockdown.
      siRNA-mediated knockdown of the imatinib target c-Abl resulted in an increased
      ERK phosphorylation at basal conditions, with no further increase in response to
      imatinib. Imatinib-induced cell survival of tunicamycin-treated cells was
      partially mediated by ERK activation. We have concluded that imatinib promotes
      LRP1-dependent ERK activation, possibly via inhibition of c-Abl, and that this
      could contribute to the pro-survival effects of imatinib on beta-cells. 

PMID- 24865477
TI  - Methylmalonic acidemia: a megamitochondrial disorder affecting the kidney.
AB  - BACKGROUND: Classical (or isolated) methylmalonic acidemia (MMA) is a
      heterogeneous inborn error of metabolism most typically caused by mutations in
      the vitamin B12-dependent enzyme methylmalonyl-CoA mutase (MUT). With the
      improved survival of individuals with MMA, chronic kidney disease has become
      recognized as part of the disorder. The precise description of renal pathology in
      MMA remains uncertain. METHODS: Light microscopy, histochemical, and
      ultrastructural studies were performed on the native kidney obtained from a 19
      year-old patient with mut MMA who developed end stage renal disease and underwent
      a combined liver-kidney transplantation. RESULTS: The light microscopy study of
      the renal parenchyma in the MMA kidney revealed extensive interstitial fibrosis,
      chronic inflammation, and tubular atrophy. Intact proximal tubules were
      distinguished by the widespread formation of large, circular, pale mitochondria
      with diminished cristae. Histochemical preparations showed a reduction of
      cytochrome c oxidase and NADH activities, and the electron microscopy analysis
      demonstrated loss of cytochrome c enzyme activity in these enlarged mitochondria.
      CONCLUSIONS: Our results demonstrate that the renal pathology of MMA is
      characterized by megamitochondria formation in the proximal tubules in concert
      with electron transport chain dysfunction. Our findings suggest therapies that
      target mitochondrial function as a treatment for the chronic kidney disease of
      MMA.

PMID- 24865479
TI  - Congenital cataracts following total parenteral nutrition (TPN) use during
      pregnancy.
AB  - We describe a case of congenital cataracts in a newborn whose mother received
      total parenteral nutrition (TPN) throughout her pregnancy. We discuss the
      potential mechanisms by which TPN may have been causally linked to cataract
      formation. 

PMID- 24865478
TI  - Acute and chronic antibody-mediated rejection in pediatric kidney
      transplantation.
AB  - Acute antibody-mediated rejection is a diagnostic challenge in renal
      transplantation medicine. However, it is an important diagnosis to make, since
      chronic antibody-mediated rejection (CAMR) is the main cause of long-term graft
      loss. Antibody-mediated rejection is diagnosed by detecting donor-specific
      antibodies (DSAs) in the blood in combination with observing typical
      histomorphological signs in kidney biopsy, as described in the Banff
      classification. Therapy is based on the removal of DSAs by administering
      intravenous immunoglobulins (IVIGs), plasmapheresis, or immunoadsorption.
      Reoccurrence of antibodies is diminished by the use of rituximab, increased
      immunosuppression, and in some cases additional experimental substances. A
      combination of these techniques has been shown to be successful in the majority
      of cases of acute and chronic antibody-mediated rejection. Routine DSA monitoring
      is warranted for early detection of antibody-mediated rejection. 

PMID- 24865482
TI  - Evaluation of adherence to a nutrition-screening programme over a 5-year period.
AB  - BACKGROUND: Nutrition screening using the Malnutrition Universal Screening Tool
      (MUST) was implemented for adult patients in 2006. The aim of this study was to
      assess adherence to the screening programme over a 5-year period after a targeted
      approach to training ward staff. SUBJECTS/METHODS: Following the implementation
      of MUST on 32 wards, regular audits were carried out. Data on completion rates at
      ward level were collected by nutrition link nurses and submitted electronically
      for collation. RESULTS: Data on MUST were collected on a total of 17 876 patients
      during this period. Mean percentage of patients screened with a moderate or high
      risk of malnutrition was 19% in those screened within 24 h after admission and
      28% in those screened at 7 days. Twenty percent of patients had an uncompleted
      MUST score at 24 h after admission and 15% were uncompleted after 7 inpatient
      days. After implementation, half the hospital population were being screened on
      admission. However, a number of wards were neither reporting the data nor
      completing the screening process. Following targeted training on wards, screening
      rates improved in 2009 and the number of patients screened improved as ward
      engagement increased. CONCLUSION: Audit has been fundamental in the
      implementation of MUST and has allowed training, additional time and educational
      resources to be allocated to specific wards to facilitate improvements in
      screening. Lead nurse support and monitoring has improved adherence rates and
      facilitated an increase in the identification of patients at moderate and high
      risk of malnutrition.

PMID- 24865481
TI  - Added value of different metabolic syndrome definitions for predicting
      cardiovascular disease and mortality events among elderly population: Tehran
      Lipid and Glucose Study.
AB  - BACKGROUND/OBJECTIVES: To examine the association between the different
      definitions of metabolic syndrome (MetS) and the prediction of incident
      cardiovascular disease (CVD) and mortality events and to determine whether the
      concept of MetS adds to traditional risk factors among elderly Iranians.
      SUBJECTS/METHODS: The association between MetS and outcomes was examined in 922
      adults aged ?65 years, free of CVD at baseline, using multivariate Cox
      proportional hazards models. To examine whether MetS could enhance prediction of
      outcomes beyond that achieved by risk factors; the net reclassification
      improvement index was used. RESULTS: During a median follow-up of 9.9 years, 207
      CVD events and 193 deaths (82 CVD deaths) occurred. World health organization
      (WHO) and the joint interim statement (JIS) definitions were shown to be the
      strongest predictors of CVD events. The WHO definition predicted CVD and all
      cause mortality events (hazard ratio (HR)=1.55 (95% confidence interval (CI)=1.15
      2.09) and 2.08 (95% CI=1.23-3.51), respectively) and the JIS definition showed a
      risk for CVD mortality (HR=1.65 (95% CI=1.03-2.65)). Different definitions of
      MetS did not add to traditional risk factors in the prediction of different
      outcomes. CONCLUSIONS: The WHO definition was the strongest predictor of CVD and
      mortality outcomes; however, none of the MetS definitions provided added value to
      traditional risk factors.

PMID- 24865480
TI  - Associations of dietary intake patterns identified using reduced rank regression
      with markers of arterial stiffness among youth with type 1 diabetes.
AB  - BACKGROUND/OBJECTIVES: Youth with type 1 diabetes (T1DM) are at substantially
      increased risk for adverse vascular outcomes, but little is known about the
      influence of dietary behavior on cardiovascular disease (CVD) risk profile. We
      aimed to identify dietary intake patterns associated with CVD risk factors and
      evaluate their impact on arterial stiffness (AS) measures collected thereafter in
      a cohort of youth with T1DM. SUBJECTS/METHODS: Baseline diet data from a food
      frequency questionnaire and CVD risk factors (triglycerides, low density
      lipoprotein-cholesterol, systolic blood pressure, hemoglobin A1c, C-reactive
      protein and waist circumference) were available for 1153 youth aged ?10 years
      with T1DM from the SEARCH for Diabetes in Youth Study. A dietary intake pattern
      was identified using 33 food groups as predictors and six CVD risk factors as
      responses in reduced rank regression (RRR) analysis. Associations of this RRR
      derived dietary pattern with AS measures (augmentation index (AIx75), n=229;
      pulse wave velocity, n=237; and brachial distensibility, n=228) were then
      assessed using linear regression. RESULTS: The RRR-derived pattern was
      characterized by high intakes of sugar-sweetened beverages (SSB) and diet soda,
      eggs, potatoes and high-fat meats and low intakes of sweets/desserts and low-fat
      dairy; major contributors were SSB and diet soda. This pattern captured the
      largest variability in adverse CVD risk profile and was subsequently associated
      with AIx75 (beta=0.47; P<0.01). The mean difference in AIx75 concentration
      between the highest and the lowest dietary pattern quartiles was 4.3% in fully
      adjusted model. CONCLUSIONS: Intervention strategies to reduce consumption of
      unhealthy foods and beverages among youth with T1DM may significantly improve CVD
      risk profile and ultimately reduce the risk for AS.

PMID- 24865483
TI  - Associations between 25-hydroxyvitamin D levels and pregnancy outcomes: a
      prospective observational study in southern China.
AB  - BACKGROUND/OBJECTIVES: Observational studies relating 25-hydroxyvitamin D
      (25(OH)D) and pregnancy outcomes have reported conflicting results. The aim was
      to assess maternal 25(OH)D status and its association with pregnancy outcomes. A
      prospective observational study was carried out in Guangzhou city (23 oN), China.
      SUBJECTS/METHODS: Pregnant women (n=2960) and healthy controls (n=100) were
      recruited at a teaching hospital. Maternal 25(OH)D levels were measured at 16-20
      week gestation. The pregnant women, if met inclusion and exclusion criteria, were
      enrolled in further analysis for pregnancy outcomes (n=1953). RESULTS: Mean serum
      25(OH)D in pregnant women was 27.03+/-7.92 ng/ml. In total, 18.9 and 48.6% of
      pregnant women had low (25(OH)D less than or equal to 20 ng/ml) and medium level
      (25(OH)D 21-29 ng/ml) of vitamin D, respectively. 25(OH)D was highest in summer
      and lowest in winter, which showed a positive correlation with temperature
      (R=0.942) and calcium (R=0.074). Most maternal outcomes (premature rupture of
      membranes break, polyhydramnios, oligohydramnios, pre-eclampsia, cesarean
      section), fetal outcomes (spontaneous abortions, medically induced labor, fetal
      death, fetal distress, fetal growth restriction) and neonatal outcomes
      (malformations, birth weight and height, low birth weight, macrosomia, small-for
      gestational age, score of Apgar 1',5', asphyxia of newborn) were not
      significantly different between groups, but prevalence of gestational diabetes
      (adjusted odds ratio (OR) 1.017; 95% confidence interval (CI) 1.002-1.033) and
      preterm delivery (adjusted OR 1.038; 95% CI 1.018-1.059) in high level group
      (25(OH)D ?30 ng/ml) was higher than that in low and medium level groups.
      CONCLUSIONS: The prevalence of low level of vitamin D (serum 25OHD ?20 ng/ml) was
      18.9% among pregnant women in southern China. There were no significant
      differences in most adverse pregnancy outcomes among pregnant women with
      different levels of vitamin D at 16-20-week gestation except for higher
      prevalence of gestational diabetes and preterm delivery in women with high level
      of vitamin D, possibly related to the older age and higher body mass index of
      this group.

PMID- 24865484
TI  - Combinatorial flexibility of cytokine function during human T helper cell
      differentiation.
AB  - In an inflammatory microenvironment, multiple cytokines may act on the same
      target cell, creating the possibility for combinatorial interactions. How these
      may influence the system-level function of a given cytokine is unknown. Here we
      show that a single cytokine, interferon (IFN)-alpha, can generate multiple
      transcriptional signatures, including distinct functional modules of variable
      flexibility, when acting in four cytokine environments driving distinct T helper
      cell differentiation programs (Th0, Th1, Th2 and Th17). We provide experimental
      validation of a chemokine, cytokine and antiviral modules differentially induced
      by IFN-alpha in Th1, Th2 and Th17 environments. Functional impact is demonstrated
      for the antiviral response, with a lesser IFN-alpha-induced protection to HIV-1
      and HIV-2 infection in a Th17 context. Our results reveal that a single cytokine
      can induce multiple transcriptional and functional programs in different
      microenvironments. This combinatorial flexibility creates a previously
      unrecognized diversity of responses, with potential impact on disease
      physiopathology and cytokine therapy. 

PMID- 24865487
TI  - The application of an emerging technique for protein-protein interaction
      interface mapping: the combination of photo-initiated cross-linking protein
      nanoprobes with mass spectrometry.
AB  - Protein-protein interaction was investigated using a protein nanoprobe capable of
      photo-initiated cross-linking in combination with high-resolution and tandem mass
      spectrometry. This emerging experimental approach introduces photo-analogs of
      amino acids within a protein sequence during its recombinant expression,
      preserves native protein structure and is suitable for mapping the contact
      between two proteins. The contact surface regions involved in the well
      characterized interaction between two molecules of human 14-3-3zeta regulatory
      protein were used as a model. The employed photo-initiated cross-linking
      techniques extend the number of residues shown to be within interaction distance
      in the contact surface of the 14-3-3zeta dimer (Gln8-Met78). The results of this
      study are in agreement with our previously published data from molecular dynamic
      calculations based on high-resolution chemical cross-linking data and
      Hydrogen/Deuterium exchange mass spectrometry. The observed contact is also in
      accord with the 14-3-3zeta X-ray crystal structure (PDB 3dhr). The results of the
      present work are relevant to the structural biology of transient interaction in
      the 14-3-3zeta protein, and demonstrate the ability of the chosen methodology
      (the combination of photo-initiated cross-linking protein nanoprobes and mass
      spectrometry analysis) to map the protein-protein interface or regions with a
      flexible structure. 

PMID- 24865488
TI  - Genetic isolation among the northwestern, southwestern and central-eastern Indian
      Ocean populations of the pronghorn spiny lobster Panulirus penicillatus.
AB  - The pronghorn spiny lobster Panulirus penicillatus is a highly valuable species
      which is widely distributed in Indo-West Pacific and Eastern Pacific regions.
      Mitochondrial DNA control region sequences (566-571 bp) were determined to
      investigate the population genetic structure of this species in the Indian Ocean.
      In total, 236 adult individuals of Panulirus penicillatus were collected from
      five locations in the Indian Ocean region. Almost all individuals had a unique
      haplotype. Intrapopulation haplotype (h) and nucleotide (pi) diversities were
      high for each locality, ranging from h = 0.9986-1.0000 and pi = 0.031593
      0.043441. We observed distinct genetic isolation of population located at the
      northwestern and southwestern edge of the species range. Gene flow was found
      within localities in the central and eastern region of the Indian Ocean, probably
      resulting from an extended planktonic larval stage and prevailing ocean currents.

PMID- 24865486
TI  - A simple three-step method for design and affinity testing of new antisense
      peptides: an example of erythropoietin.
AB  - Antisense peptide technology is a valuable tool for deriving new biologically
      active molecules and performing peptide-receptor modulation. It is based on the
      fact that peptides specified by the complementary (antisense) nucleotide
      sequences often bind to each other with a higher specificity and efficacy. We
      tested the validity of this concept on the example of human erythropoietin, a
      well-characterized and pharmacologically relevant hematopoietic growth factor.
      The purpose of the work was to present and test simple and efficient three-step
      procedure for the design of an antisense peptide targeting receptor-binding site
      of human erythropoietin. Firstly, we selected the carboxyl-terminal receptor
      binding region of the molecule (epitope) as a template for the antisense peptide
      modeling; Secondly, we designed an antisense peptide using mRNA transcription of
      the epitope sequence in the 3'->5' direction and computational screening of
      potential paratope structures with BLAST; Thirdly, we evaluated sense-antisense
      (epitope-paratope) peptide binding and affinity by means of fluorescence
      spectroscopy and microscale thermophoresis. Both methods showed similar Kd values
      of 850 and 816 uM, respectively. The advantages of the methods were: fast
      screening with a small quantity of the sample needed, and measurements done
      within the range of physicochemical parameters resembling physiological
      conditions. Antisense peptides targeting specific erythropoietin region(s) could
      be used for the development of new immunochemical methods. Selected antisense
      peptides with optimal affinity are potential lead compounds for the development
      of novel diagnostic substances, biopharmaceuticals and vaccines. 

PMID- 24865489
TI  - Searching for "environmentally-benign" antifouling biocides.
AB  - As the result of the ecological impacts from the use of tributyltins (TBT) in
      shipping, environmental legislation for the registration of chemicals for use in
      the environment has grown to a monumental challenge requiring product dossiers to
      include information on the environmental fate and behavior of any chemicals.
      Specifically, persistence, bioaccumulation and toxicity, collectively known as
      PBT, are properties of concern in the assessment of chemicals. However, existing
      measurements of PBT properties are a cumbersome and expensive process, and thus
      not applied in the early stages of the product discovery and development.
      Inexpensive methods for preliminary PBT screening would minimize risks arising
      with the subsequent registration of products. In this article, we evaluated the
      PBT properties of compounds reported to possess anti-fouling properties using
      QSAR (quantitative structure-activity relationship) prediction programs such as
      BIOWINTM (a biodegradation probability program), KOWWINTM (log octanol-water
      partition coefficient calculation program) and ECOSARTM (Ecological Structure
      Activity Relationship Programme). The analyses identified some small (Mr < 400)
      synthetic and natural products as potential candidates for environmentally benign
      biocides. We aim to demonstrate that while these methods of estimation have
      limitations, when applied with discretion, they are powerful tools useful in the
      early stages of research for compound selection for further development as anti
      foulants. 

PMID- 24865490
TI  - Proteome analysis of subsarcolemmal cardiomyocyte mitochondria: a comparison of
      different analytical platforms.
AB  - Mitochondria are complex organelles that play critical roles in diverse aspects
      of cellular function. Heart disease and a number of other pathologies are
      associated with perturbations in the molecular machinery of the mitochondria.
      Therefore, comprehensive, unbiased examination of the mitochondrial proteome
      represents a powerful approach toward system-level insights into disease
      mechanisms. A crucial aspect in proteomics studies is design of bioanalytical
      strategies that maximize coverage of the complex repertoire of mitochondrial
      proteins. In this study, we evaluated the performance of gel-based and gel-free
      multidimensional platforms for profiling of the proteome in subsarcolemmal
      mitochondria harvested from rat heart. We compared three different
      multidimensional proteome fractionation platforms: polymeric reversed-phase
      liquid chromatography at high pH (PLRP), sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis (SDS-PAGE), and isoelectric focusing (IEF) separations
      combined with liquid chromatography-mass spectrometry/mass spectrometry (LC
      MS/MS), and bioinformatics for protein identification. Across all three
      platforms, a total of 1043 proteins were identified. Among the three
      bioanalytical strategies, SDS-PAGE followed by LC-MS/MS provided the best
      coverage of the mitochondrial proteome. With this platform, 890 proteins with
      diverse physicochemical characteristics were identified; the mitochondrial
      protein panel encompassed proteins with various functional roles including
      bioenergetics, protein import, and mitochondrial fusion. Taken together, results
      of this study provide a large-scale view of the proteome in subsarcolemmal
      mitochondria from the rat heart, and aid in the selection of optimal
      bioanalytical platforms for differential protein expression profiling of
      mitochondria in health and disease. 

PMID- 24865485
TI  - Molecular mechanisms of liver fibrosis in HIV/HCV coinfection.
AB  - Chronic hepatitis C virus (HCV) infection is an important cause of morbidity and
      mortality in people coinfected with human immunodeficiency virus (HIV). Several
      studies have shown that HIV infection promotes accelerated HCV hepatic fibrosis
      progression, even with HIV replication under full antiretroviral control. The
      pathogenesis of accelerated hepatic fibrosis among HIV/HCV coinfected individuals
      is complex and multifactorial. The most relevant mechanisms involved include
      direct viral effects, immune/cytokine dysregulation, altered levels of matrix
      metalloproteinases and fibrosis biomarkers, increased oxidative stress and
      hepatocyte apoptosis, HIV-associated gut depletion of CD4 cells, and microbial
      translocation. In addition, metabolic alterations, heavy alcohol use, as well
      drug use, may have a potential role in liver disease progression. Understanding
      the pathophysiology and regulation of liver fibrosis in HIV/HCV co-infection may
      lead to the development of therapeutic strategies for the management of all
      patients with ongoing liver disease. In this review, we therefore discuss the
      evidence and potential molecular mechanisms involved in the accelerated liver
      fibrosis seen in patients coinfected with HIV and HCV. 

PMID- 24865491
TI  - Rare variants in genes encoding MuRF1 and MuRF2 are modifiers of hypertrophic
      cardiomyopathy.
AB  - Modifier genes contribute to the diverse clinical manifestations of hypertrophic
      cardiomyopathy (HCM), but are still largely unknown. Muscle ring finger (MuRF)
      proteins are a class of muscle-specific ubiquitin E3-ligases that appear to
      modulate cardiac mass and function by regulating the ubiquitin-proteasome system.
      In this study we screened all the three members of the MuRF family, MuRF1, MuRF2
      and MuRF3, in 594 unrelated HCM patients and 307 healthy controls by targeted
      resequencing. Identified rare variants were confirmed by capillary Sanger
      sequencing. The prevalence of rare variants in both MuRF1 and MuRF2 in HCM
      patients was higher than that in control subjects (MuRF1 13/594 (2.2%) vs. 1/307
      (0.3%), p = 0.04; MuRF2 22/594 (3.7%) vs. 2/307 (0.7%); p = 0.007). Patients with
      rare variants in MuRF1 or MuRF2 were younger (p = 0.04) and had greater maximum
      left ventricular wall thickness (p = 0.006) than those without such variants.
      Mutations in genes encoding sarcomere proteins were present in 19 (55.9%) of the
      34 HCM patients with rare variants in MuRF1 and MuRF2. These data strongly
      supported that rare variants in MuRF1 and MuRF2 are associated with higher
      penetrance and more severe clinical manifestations of HCM. The findings suggest
      that dysregulation of the ubiquitin-proteasome system contributes to the
      pathogenesis of HCM. 

PMID- 24865493
TI  - A view of pre-mRNA splicing from RNase R resistant RNAs.
AB  - During pre-mRNA splicing, exons in the primary transcript are precisely connected
      to generate an mRNA. Intron lariat RNAs are formed as by-products of this
      process. In addition, some exonic circular RNAs (circRNAs) may also result from
      exon skipping as by-products. Lariat RNAs and circRNAs are both RNase R resistant
      RNAs. RNase R is a strong 3' to 5' exoribonuclease, which efficiently degrades
      linear RNAs, such as mRNAs and rRNAs; therefore, the circular parts of lariat
      RNAs and the circRNAs can be segregated from eukaryotic total RNAs by their RNase
      R resistance. Thus, RNase R resistant RNAs could provide unexplored splicing
      information not available from mRNAs. Analyses of these RNAs identified repeating
      splicing phenomena, such as re-splicing of mature mRNAs and nested splicing.
      Moreover, circRNA might function as microRNA sponges. There is an enormous
      variety of endogenous circRNAs, which are generally synthesized in cells and
      tissues. 

PMID- 24865492
TI  - Adipose-derived stem cells: a review of signaling networks governing cell fate
      and regenerative potential in the context of craniofacial and long bone skeletal
      repair.
AB  - Improvements in medical care, nutrition and social care are resulting in a
      commendable change in world population demographics with an ever increasing skew
      towards an aging population. As the proportion of the world's population that is
      considered elderly increases, so does the incidence of osteodegenerative disease
      and the resultant burden on healthcare. The increasing demand coupled with the
      limitations of contemporary approaches, have provided the impetus to develop
      novel tissue regeneration therapies. The use of stem cells, with their potential
      for self-renewal and differentiation, is one potential solution. Adipose-derived
      stem cells (ASCs), which are relatively easy to harvest and readily available
      have emerged as an ideal candidate. In this review, we explore the potential for
      ASCs to provide tangible therapies for craniofacial and long bone skeletal
      defects, outline key signaling pathways that direct these cells and describe how
      the developmental signaling program may provide clues on how to guide these cells
      in vivo. This review also provides an overview of the importance of establishing
      an osteogenic microniche using appropriately customized scaffolds and delineates
      some of the key challenges that still need to be overcome for adult stem cell
      skeletal regenerative therapy to become a clinical reality. 

PMID- 24865494
TI  - Maize ZmRACK1 is involved in the plant response to fungal phytopathogens.
AB  - The receptor for activated C kinase 1 (RACK1) belongs to a protein subfamily
      containing a tryptophan-aspartic acid-domain (WD) repeat structure. Compelling
      evidence indicates that RACK1 can interact with many signal molecules and affect
      different signal transduction pathways. In this study, we cloned a maize RACK1
      gene (ZmRACK1) by RT-PCR. The amino acid sequence of ZmRACK1 had seven WD repeats
      in which there were typical GH (glycine-histidine) and WD dipeptides. Comparison
      with OsRACK1 from rice revealed 89% identity at the amino acid level. Expression
      pattern analysis by RT-PCR showed that ZmRACK1 was expressed in all analyzed
      tissues of maize and that its transcription in leaves was induced by abscisic
      acid and jasmonate at a high concentration. Overexpression of ZmRACK1 in maize
      led to a reduction in symptoms caused by Exserohilum turcicum (Pass.) on maize
      leaves. The expression levels of the pathogenesis-related protein genes, PR-1 and
      PR-5, increased 2.5-3 times in transgenic maize, and reactive oxygen species
      production was more active than in the wild-type. Yeast two-hybrid assays showed
      that ZmRACK1 could interact with RAC1, RAR1 and SGT1. This study and previous
      work leads us to believe that ZmRACK1 may form a complex with regulators of plant
      disease resistance to coordinate maize reactions to pathogens. 

PMID- 24865496
TI  - Peptide nanofibrils as enhancers of retroviral gene transfer.
AB  - Amyloid fibrils are polypeptide-based polymers that are typically associated with
      neurodegenerative disorders such as Alzheimer's disease. More recently, it has
      become clear that amyloid fibrils also fulfill functional roles in hormone
      storage and biosynthesis. Furthermore, it has been demonstrated that semen
      contains abundant levels of polycationic amyloid fibrils. The natural role of
      these seminal amyloids remains elusive. Strikingly, however, they drastically
      enhance HIV-1 infection and may be exploited by the virus to increase its sexual
      transmission rate. Their strong activity in enhancing HIV-1 infection suggests
      that seminal amyloid might also promote transduction by retroviral vectors.
      Indeed, SEVI (semen-derived enhancer of virus infection), the best characterized
      seminal amyloid, boosts retroviral gene transfer more efficiently than
      conventional additives. However, the use of SEVI as laboratory tool for efficient
      retroviral gene transfer is limited because the polypeptide monomers are
      relatively expensive to produce. Furthermore, standardized production of SEVI
      fibrils with similar high activities is difficult to achieve because of the
      stochastic nature of the amyloid assembly process. These obstacles can be
      overcome by recently identified smaller peptides that spontaneously self-assemble
      into nanofibrils. These nanofibrils increase retroviral gene transfer even more
      efficiently than SEVI, are easy to produce and to handle, and seem to be safe as
      assessed in an ex vivo gene transfer study. Furthermore, peptide-based
      nanofibrils allow to concentrate viral particles by low-speed centrifugation.
      Specific adaption and customization of self-assembling peptides might lead to
      novel nanofibrils with versatile biological functions, e.g., targeted retroviral
      gene transfer or drug delivery.

PMID- 24865497
TI  - Aerosol delivery of DNA/liposomes to the lung for cystic fibrosis gene therapy.
AB  - Abstract Lung gene therapy is being evaluated for a range of acute and chronic
      diseases, including cystic fibrosis (CF). As these therapies approach clinical
      realization, it is becoming increasingly clear that the ability to efficiently
      deliver gene transfer agents (GTAs) to target cell populations within the lung
      may prove just as critical as the gene therapy formulation itself in terms of
      generating positive clinical outcomes. Key to the success of any aerosol gene
      therapy is the interaction between the GTA and nebulization device. We evaluated
      the effects of aerosolization on our preferred formulation, plasmid DNA (pDNA)
      complexed with the cationic liposome GL67A (pDNA/GL67A) using commercially
      available nebulizer devices. The relatively high viscosity (6.3+/-0.1 cP) and
      particulate nature of pDNA/GL67A formulations hindered stable aerosol generation
      in ultrasonic and vibrating mesh nebulizers but was not problematic in the jet
      nebulizers tested. Aerosol size characteristics varied significantly between
      devices, but the AeroEclipse II nebulizer operating at 50 psi generated stable
      pDNA/GL67A aerosols suitable for delivery to the CF lung (mass median aerodynamic
      diameter 3.4+/-0.1 MUm). Importantly, biological function of pDNA/GL67A
      formulations was retained after nebulization, and although aerosol delivery rate
      was lower than that of other devices (0.17+/-0.01 ml/min), the breath-actuated
      AeroEclipse II nebulizer generated aerosol only during the inspiratory phase and
      as such was more efficient than other devices with 83+/-3% of generated aerosol
      available for patient inhalation. On the basis of these results, we have selected
      the AeroEclipse II nebulizer for the delivery of pDNA/GL67A formulations to the
      lungs of CF patients as part of phase IIa/b clinical studies. 

PMID- 24865498
TI  - Noninvasive anaplastic thyroid carcinoma: report of a case and literature review.
AB  - Anaplastic thyroid carcinoma (ATC) is an uncommon thyroid malignancy. Noninvasive
      ATC is a rare, surgically resectable variant with only four reported cases. We
      report a case of an 81-year-old man who presented with a 3.1 cm right thyroid
      lobe mass that on fine-needle aspiration biopsy was diagnosed as an ATC.
      Preoperative imaging revealed an encapsulated thyroid tumor without evidence of
      invasion of surrounding structures and no locoregional and distant metastases. A
      total thyroidectomy was performed that by histologic and immunohistochemical
      evaluation was diagnostic for a noninvasive ATC. Given the diagnosis of
      noninvasive ATC, adjuvant therapy was not administered. At 14 months following
      diagnosis, the patient remains disease free based on positron emission
      tomography/computed tomography imaging. A review of the outcomes of similar cases
      reported in the literature, as well as observations from our case, suggest a
      favorable prognosis for patients with noninvasive ATC. Noninvasive ATC may
      represent a distinct subset of resectable ATCs with an improved prognosis. The
      recently published American Thyroid Association (ATA) Guidelines for Management
      of Patients with ATC do not include this specific form of ATC. We encourage other
      authors to report similar cases in order to determine whether noninvasive ATC
      should be considered as a separate disease entity from the traditional highly
      lethal form of ATC. 

PMID- 24865499
TI  - Emergency medical services management of ST-segment elevation myocardial
      infarction in the United States--a report from the American Heart Association
      Mission: Lifeline Program.
AB  - OBJECTIVE: ST-segment elevation myocardial infarction (STEMI) is a major cause of
      morbidity and mortality in the United States. Emergency medical services (EMS)
      agencies play a critical role in its initial identification and treatment. We
      conducted this study to assess EMS management of STEMI care in the United States.
      METHODS: A structured questionnaire was administered to leaders of EMS agencies
      to define the elements of STEMI care related to 4 core measures: (1)
      electrocardiogram (ECG) capability at the scene, (2) destination protocols, (3)
      catheterization laboratory activation before hospital arrival, and (4) 12-lead
      ECG quality review. Geographic areas were grouped into large metropolitan, small
      metropolitan, micropolitan, and noncore (or rural) by using Urban Influence
      Codes, with a stratified analysis. RESULTS: Data were included based on responses
      from 5296 EMS agencies (36% of those in the United States) serving 91% of the US
      population, with at least 1 valid response from each of the 50 states and the
      District of Columbia. Approximately 63% of agencies obtained ECGs at the scene
      using providers trained in ECG acquisition and interpretation. A total of 46% of
      EMS systems used protocols to determine hospital destination, cardiac
      catheterization laboratory activation, and communications with the receiving
      hospital. More than 75% of EMS systems used their own agency funds to purchase
      equipment, train personnel, and provide administrative oversight. A total of 49%
      of agencies have quality review programs in place. In general, EMS systems
      covering higher population densities had easier access to resources needed to
      maintain STEMI systems of care. Emergency medical services systems that have
      adopted all 4 core elements cover 14% of the US population. CONCLUSIONS: There
      are large differences in EMS systems of STEMI care in the United States. Most EMS
      agencies have implemented at least 1 of the 4 core elements of STEMI care, with
      many having implemented multiple elements.

PMID- 24865501
TI  - Photocatalytic degradation of indigo carmine by hydrothermally synthesized Bi2MoO
      6 in presence of EDTA.
AB  - Bi2MoO6 oxide was synthesized by hydrothermal reaction in the presence of EDTA
      under different experimental conditions (time of reaction and EDTA concentration)
      in order to obtain materials with specific textural properties. It was determined
      that the addition of EDTA influences the final physical properties of Bi2MoO6.
      The photocatalytic activity of Bi2MoO6 samples was evaluated in the degradation
      reaction of indigo carmine (IC) in aqueous solution under solar radiation type.
      The best results as photocatalyst were obtained with the sample hydrothermally
      synthesized at 150 oC for 4h in presence of a 0.031 M EDTA solution. This sample
      was able to whiten a solution of IC in a 94% after 120 min of lamp irradiation
      with t 1/2 = 31 min. In general, the samples prepared with lower concentrations
      of EDTA were the best photocatalysts. A gradual decrease in the activity was
      observed in the samples prepared with the same EDTA concentration as was
      increased in the reaction time. Beyond differences in morphology and textural
      properties of the samples prepared, the presence of EDTA by-products on the
      samples and the decomposition degree of it were important factors in determining
      the activity of the photocatalysts. Analysis of total organic carbon (TOC) of
      samples irradiated for 100 h confirmed that Bi2MoO6 oxide is able to mineralize
      the complex organic molecule of IC to CO2 and H2O in 55 %.

PMID- 24865500
TI  - Assessment and rationalization of water quality monitoring network: a
      multivariate statistical approach to the Kabbini River (India).
AB  - The establishment of an efficient surface water quality monitoring (WQM) network
      is a critical component in the assessment, restoration and protection of river
      water quality. A periodic evaluation of monitoring network is mandatory to ensure
      effective data collection and possible redesigning of existing network in a river
      catchment. In this study, the efficacy and appropriateness of existing water
      quality monitoring network in the Kabbini River basin of Kerala, India is
      presented. Significant multivariate statistical techniques like principal
      component analysis (PCA) and principal factor analysis (PFA) have been employed
      to evaluate the efficiency of the surface water quality monitoring network with
      monitoring stations as the evaluated variables for the interpretation of complex
      data matrix of the river basin. The main objective is to identify significant
      monitoring stations that must essentially be included in assessing annual and
      seasonal variations of river water quality. Moreover, the significance of
      seasonal redesign of the monitoring network was also investigated to capture
      valuable information on water quality from the network. Results identified few
      monitoring stations as insignificant in explaining the annual variance of the
      dataset. Moreover, the seasonal redesign of the monitoring network through a
      multivariate statistical framework was found to capture valuable information from
      the system, thus making the network more efficient. Cluster analysis (CA)
      classified the sampling sites into different groups based on similarity in water
      quality characteristics. The PCA/PFA identified significant latent factors
      standing for different pollution sources such as organic pollution, industrial
      pollution, diffuse pollution and faecal contamination. Thus, the present study
      illustrates that various multivariate statistical techniques can be effectively
      employed in sustainable management of water resources. HIGHLIGHTS: The
      effectiveness of existing river water quality monitoring network is assessed.
      Significance of seasonal redesign of the monitoring network is demonstrated.
      Rationalization of water quality parameters is performed in a statistical
      framework.

PMID- 24865502
TI  - Metabolic enzymes activity and histomorphology in the liver of whitefish
      (Coregonus lavaretus L.) and pike (Esox lucius L.) inhabiting a mineral
      contaminated lake.
AB  - The effects of wastewater from a mining and ore-dressing mill on fish in Lake
      Kostomukshskoe, which is used as a cesspool of circulating water and for storage
      of industrial wastes produced by the Kostomuksha mining and ore-dressing mill in
      northwest Russia, were studied. The lake is characterized by heavy
      mineralization, high pH, elevated levels of K(+), Li(+), SO4 (2-), NO(2-), Cl(-),
      Li, Mn, and Ni, and the presence of a fine-dispersed mechanical suspension. To
      assess the impact of contamination on fish and determine the mechanisms of their
      adaptation, we investigated the biochemical indices and histology of the liver of
      whitefish (Coregonus lavaretus L.) and pike (Esox lucius L.) inhabiting Lake
      Kostomukshskoe, downstream Lake Koyvas (64 degrees  47' 30 degrees  59'), and
      Lake Kamennoe, which is located in a nature preserve and has not been affected by
      anthropogenic activity (64 degrees  28' 30 degrees  13'). Changes were detected
      in the activity of metabolic enzymes (cytochrome c oxidase (COX), lactate
      dehydrogenase, and glucose-6-phosphate dehydrogenase) in the liver. Specifically,
      the COX activity in the liver of both fish species from the contaminated lake
      decreased, indicating a low level of aerobic metabolism. Lipid infiltration was
      the most visible and widespread change observed in the liver of both fish
      species; therefore, it can be considered a marker of such long-term
      contamination. Lesions in pike liver demonstrated a wider range of severity than
      in those of whitefish. In summary, metabolic enzyme activity and histomorphology
      of the liver of whitefish and pike differed among lakes in a species-specific
      manner. The changes in enzyme activity and histomorphological alterations in fish
      that were observed can be applied for evaluation of freshwater systems that may
      be subjected to mineral pollution.

PMID- 24865503
TI  - Three decades of environmental specimen banking at the National Institute for
      Environmental Studies, Japan.
AB  - After two decades operation of the initial environmental specimen banking, a new
      program, Environmental Time Capsule Program, started in 2002 as a government
      supported long-term program to construct a firm scientific basis for various
      environmental research studies. The program consists of long-term environmental
      specimen banking activity and specimen collection of endangered wildlife and is
      based on cryogenic sample preservation facility called Environmental Time Capsule
      building, which completed construction in 2004. After 9 years of extensive
      research, research focuses have been selected and the program was reorganized to
      the environmental sample collection part and endangered wildlife collection part
      in 2011. Due to huge environmental disaster caused by the Great East Japan
      earthquake and the tsunami as well as subsequent nuclear power plant accident at
      Fukushima, a new sampling and monitoring program started at affected areas in
      collaboration with the reorganized environmental sample collection and archiving
      program. Outlines of the quality assurance and quality control (QA/QC) activities
      in the program and future perspective under related international activities,
      particularly Stockholm Convention, are reported.

PMID- 24865504
TI  - Environmental effects of soil contamination by shale fuel oils.
AB  - Estonia is currently one of the leading producers of shale oils in the world.
      Increased production, transportation and use of shale oils entail risks of
      environmental contamination. This paper studies the behaviour of two shale fuel
      oils (SFOs)--'VKG D' and 'VKG sweet'--in different soil matrices under natural
      climatic conditions. Dynamics of SFOs' hydrocarbons (C10-C40), 16 PAHs, and a
      number of soil heterotrophic bacteria in oil-spiked soils was investigated during
      the long-term (1 year) outdoor experiment. In parallel, toxicity of aqueous
      leachates of oil-spiked soils to aquatic organisms (crustaceans Daphnia magna and
      Thamnocephalus platyurus and marine bacteria Vibrio fischeri) and terrestrial
      plants (Sinapis alba and Hordeum vulgare) was evaluated. Our data showed that in
      temperate climate conditions, the degradation of SFOs in the oil-contaminated
      soils was very slow: after 1 year of treatment, the decrease of total
      hydrocarbons' content in the soil did not exceed 25 %. In spite of the comparable
      chemical composition of the two studied SFOs, the VKG sweet posed higher hazard
      to the environment than the heavier fraction (VKG D) due to its higher mobility
      in the soil as well as higher toxicity to aquatic and terrestrial species. Our
      study demonstrated that the correlation between chemical parameters (such as
      total hydrocarbons or total PAHs) widely used for the evaluation of the soil
      pollution levels and corresponding toxicity to aquatic and terrestrial organisms
      was weak.

PMID- 24865505
TI  - Estimation methods and monitoring network issues in the quantitative estimation
      of land-based COD and TN loads entering the sea: a case study in Qingdao City,
      China.
AB  - At present, the monitoring network of China cannot provide sufficient data to
      estimate land-based pollutant loads that enter the sea, and estimation methods
      are imprecisely used. In this study, the selection of monitoring stations,
      monitoring frequency, and pollutant load estimation methods was studied in
      Qingdao City, a typical coastal city in China, taken as an example. Land-based
      pollutant loads from Qingdao were estimated, and load distribution, density, and
      composition were analyzed to identify the key pollution source regions (SRs) that
      need to be monitored and controlled. Results show that the administrative land
      area of Qingdao can be divided into 25 sea-sink source regions (SSRs). A total of
      14 more rivers and 62 industrial enterprises should be monitored to determine the
      comprehensive pollutant loads of the city. Furthermore, the monitoring frequency
      of rivers should not be less than three times/year; a monitoring frequency of
      five or more times is preferable. The findings on pollutant load estimation with
      the use of different estimation methods substantially vary; estimation results
      with the use of ratio-based methods were 10 and 22 % higher than those with the
      use of monitoring-based methods in terms of chemical oxygen demand (COD) and
      total nitrogen (TN), respectively. None-point sources contributed the majority of
      the pollutant loads at about 70 % of the total COD and 60 % of the total TN.

PMID- 24865507
TI  - Zinc and iron concentration QTL mapped in a Triticum spelta * T. aestivum cross.
AB  - KEY MESSAGE: Ten QTL underlying the accumulation of Zn and Fe in the grain were
      mapped in a set of RILs bred from the cross Triticum spelta * T. aestivum . Five
      of these loci (two for Zn and three for Fe) were consistently detected across
      seven environments. The genetic basis of accumulation in the grain of Zn and Fe
      was investigated via QTL mapping in a recombinant inbred line (RIL) population
      bred from a cross between Triticum spelta and T. aestivum. The concentration of
      the two elements was measured from grain produced in three locations over two
      consecutive cropping seasons and from a greenhouse trial. The range in Zn and Fe
      concentration across the RILs was, respectively, 18.8-73.5 and 25.3-59.5 ppm, and
      the concentrations of the two elements were positively correlated with one
      another (rp =+0.79). Ten QTL (five each for Zn and Fe accumulation) were
      detected, mapping to seven different chromosomes. The chromosome 2B and 6A grain
      Zn QTL were consistently expressed across environments. The proportion of the
      phenotype explained (PVE) by QZn.bhu-2B was >16 %, and the locus was closely
      linked to the SNP marker 1101425|F|0, while QZn.bhu-6A (7.0 % PVE) was closely
      linked to DArT marker 3026160|F|0. Of the five Fe QTL detected, three, all
      mapping to chromosome 1A were detected in all seven environments. The PVE for
      QFe.bhu-3B was 26.0 %.

PMID- 24865509
TI  - Post exertional hematuria.
AB  - The incidence of exercise-induced hematuria is reported to be between 5% and 25%
      and available literature suggests that it lasts for a few hours to a maximum of 3
      days. We analyzed the urine sediment of healthy participants between the age of
      20 and 50 years before and after a 5 km run. Anyone with abnormal pre-exercise
      sediment was excluded from the study. Of 491 participants, 59 (12%) developed
      post exercise hematuria when the run had to be completed in allotted time.
      However, when the run was completed without time limit, only 1.3% (4 of 316)
      developed hematuria (p < 0.001). We found that the younger participants (age < 30
      years) had a significantly higher incidence of hematuria as compared to their
      older compatriots (p = 0.019). The mean duration of hematuria was 1.98 +/- 1.89
      days and 81% of the participants cleared their hematuria within 3 days. In 12% it
      lasted between 3 and 7 days and in 7% it continued beyond 7 days. Three
      individuals had persistence of hematuria beyond day 14 and all these were found
      to have primary glomerular disease on renal biopsy [two had IgA nephropathy and
      one focal segmental glomerulosclerosis (FSGS)]. We conclude that exercise-induced
      hematuria can last up to a fortnight. However, if it persists beyond a fortnight,
      it is unlikely to be functional and an underlying cause is likely. Hematuria
      following exercise seems to be related to the intensity of effort during exercise
      rather than its duration.

PMID- 24865508
TI  - QTL mapping of black rot (Guignardia bidwellii) resistance in the grapevine
      rootstock 'Borner' (V. riparia Gm183 * V. cinerea Arnold).
AB  - KEY MESSAGE: In the grapevine cultivar 'Borner' QTLs for black rot resistance
      were detected consistently in several independent experiments. For one QTL on
      chromosome 14 closely linked markers were developed and a detailed map provided.
      Black rot is a serious grapevine disease that causes substantial yield loss under
      unfavourable conditions. All traditional European grapevine cultivars are
      susceptible to the causative fungus Guignardia bidwellii which is native to North
      America. The cultivar 'Borner', an interspecific hybrid of V. riparia and V.
      cinerea, shows a high resistance to black rot. Therefore, a mapping population
      derived from the cross of the susceptible breeding line V3125 ('Schiava grossa' *
      'Riesling') with 'Borner' was used to carry out QTL analysis. A resistance test
      was established based on potted plants which were artificially inoculated in a
      climate chamber with in vitro produced G. bidwellii spores. Several rating
      systems were developed and tested. Finally, a five class scheme was applied for
      scoring the level of resistance. A major QTL was detected based on a previously
      constructed genetic map and data from six independent resistance tests in the
      climate chamber and one rating of natural infections in the field. The QTL is
      located on linkage group 14 (Rgb1) and explained up to 21.8 % of the phenotypic
      variation (LOD 10.5). A second stable QTL mapped on linkage group 16 (Rgb2; LOD
      4.2) and explained 8.5 % of the phenotypic variation. These two QTLs together
      with several minor QTLs observed on the integrated map indicate a polygenic
      nature of the black rot resistance in 'Borner'. A detailed genetic map is
      presented for the locus Rgb1 with tightly linked markers valuable for the
      development for marker-assisted selection for black rot resistance in grapevine
      breeding.

PMID- 24865506
TI  - Genetic control of grain yield and grain physical characteristics in a bread
      wheat population grown under a range of environmental conditions.
AB  - KEY MESSAGE: Genetic analysis of the yield and physical quality of wheat revealed
      complex genetic control, including strong effects of photoperiod-sensitivity
      loci. Environmental conditions such as moisture deficit and high temperatures
      during the growing period affect the grain yield and grain characteristics of
      bread wheat (Triticum aestivum L.). The aim of this study was to map quantitative
      trait loci (QTL) for grain yield and grain quality traits using a
      Drysdale/Gladius bread wheat mapping population grown under a range of
      environmental conditions in Australia and Mexico. In general, yield and grain
      quality were reduced in environments exposed to drought and/or heat stress.
      Despite large effects of known photoperiod-sensitivity loci (Ppd-B1 and Ppd-D1)
      on crop development, grain yield and grain quality traits, it was possible to
      detect QTL elsewhere in the genome. Some of these QTL were detected consistently
      across environments. A locus on chromosome 6A (TaGW2) that is known to be
      associated with grain development was associated with grain width, thickness and
      roundness. The grain hardness (Ha) locus on chromosome 5D was associated with
      particle size index and flour extraction and a region on chromosome 3B was
      associated with grain width, thickness, thousand grain weight and yield. The
      genetic control of grain length appeared to be largely independent of the genetic
      control of the other grain dimensions. As expected, effects on grain yield were
      detected at loci that also affected yield components. Some QTL displayed QTL-by
      environment interactions, with some having effects only in environments subject
      to water limitation and/or heat stress.

PMID- 24865510
TI  - Gemtuzumab ozogamicin in acute myeloid leukemia revisited.
AB  - INTRODUCTION: Gemtuzumab ozogamicin (GO) is a combination of calicheamicin and a
      recombinant humanized IgG4 antibody directed against CD33. From 2000 to 2010, it
      was approved by the FDA for treatment of relapsed, older patients with CD33(+)
      acute myeloid leukemia (AML). After withdrawal from the market, several trials
      have provided new evidence on the safety and clinical efficacy of GO. AREAS
      COVERED: In this review, we discuss pharmacological and clinical aspects of GO.
      GO was found to show benefit in AML patients as adjunct to intensive chemotherapy
      when it was given in parallel to induction therapy. The benefit was restricted to
      patients with a favorable- or an intermediate-risk cytogenetic profile. Higher
      doses of GO above 6 mg/m(2) per administration were associated with increased
      toxicity without survival benefit, whereas repetitive doses of 3 mg/m(2)
      resulting in cumulative doses of 9 mg/m(2) were well tolerated. Predictive
      markers for response to GO other than the cytogenetic profile and P-glycoprotein
      activity are still missing. EXPERT OPINION: GO as adjunct and in parallel to
      intensive induction chemotherapy does significantly improve survival end points
      in AML patients with favorable/intermediate-risk cytogenetics. A dose of 3
      mg/m(2) per administration appears safer compared with 6 mg/m(2) and even 9
      mg/m(2).

PMID- 24865511
TI  - The influence of motivational and mood states on visual attention: A
      quantification of systematic differences and casual changes in subjects' focus of
      attention.
AB  - A great number of studies have shown that different motivational and mood states
      can influence human attentional processes in a variety of ways. Yet, none of
      these studies have reliably quantified the exact changes of the attentional focus
      in order to be able to compare attentional performances based on different
      motivational and mood influences and, beyond that, to evaluate their effectivity.
      In two studies, we explored subjects' differences in the breadth and distribution
      of attention as a function of motivational and mood manipulations. In Study 1,
      motivational orientation was classified in terms of regulatory focus (promotion
      vs. prevention) and in Study 2, mood was classified in terms of valence (positive
      vs. negative). Study 1 found a 10% wider distribution of the visual attention in
      promotion-oriented subjects compared to prevention-oriented ones. The results in
      Study 2 reveal a widening of the subjects' visual attentional breadth when
      listening to happy music by 22% and a narrowing by 36% when listening to
      melancholic music. In total, the findings show that systematic differences and
      casual changes in the shape and scope of focused attention may be associated with
      different motivational and mood states. 

PMID- 24865513
TI  - Excitotoxicity Induced by Realgar in the Rat Hippocampus: the Involvement of
      Learning Memory Injury, Dysfunction of Glutamate Metabolism and NMDA Receptors.
AB  - Realgar is a type of mineral drug containing arsenic. The nervous system toxicity
      of realgar has received extensive attention. However, the underlying mechanisms
      of realgar-induced neurotoxicity have not been clearly elucidated. To explore the
      mechanisms that contribute to realgar-induced neurotoxicity, weanling rats were
      exposed to realgar (0, 0.3, 0.9, 2.7 g/kg) for 6 weeks, and cognitive ability was
      tested using the Morris water maze (MWM) test and object recognition task (ORT).
      The levels of arsenic in the blood and hippocampus were monitored. The
      ultrastructures of hippocampal neurons were observed. The levels of glutamate
      (Glu) and glutamine (Gln) in the hippocampus and hippocampal CA1 region; the
      activities of glutamine synthetase (GS) and phosphate-activated glutaminase
      (PAG); the mRNA and protein expression of glutamate transporter 1 (GLT-1),
      glutamate/aspartate transporter (GLAST), and N-methyl-D-aspartate (NMDA)
      receptors; and the level of intracellular Ca(2+) were also investigated. The
      results indicate that the rats developed deficiencies in cognitive ability after
      a 6-week exposure to realgar. The arsenic contained in realgar and the arsenic
      metabolites passed through the blood-brain barrier (BBB) and accumulated in the
      hippocampus, which resulted in the excessive accumulation of Glu in the
      extracellular space. The excessive accumulation of Glu in the extracellular space
      induced excitotoxicity, which was shown by enhanced GS and PAG activities,
      inhibition of GLT-1 mRNA and protein expression, alterations in NMDA receptor
      mRNA and protein expression, disturbance of intracellular Ca(2+) homeostasis, and
      ultrastructural changes in hippocampal neurons. In conclusion, the findings from
      our study indicate that exposure to realgar induces excitotoxicity and that the
      mechanism by which this occurs may be associated with disturbances in Glu
      metabolism and transportation and alterations in NMDA receptor expression. 

PMID- 24865515
TI  - Lost: Thomas Edison's Mood music found: new ways of listening.

PMID- 24865514
TI  - VEGF-A promotes both pro-angiogenic and neurotrophic capacities for nerve
      recovery after compressive neuropathy in rats.
AB  - Nerve recovery following injury is usually incomplete, leaving functional
      deficits. Our aim was to investigate the neural changes in pro-angiogenic, pro
      inflammatory and apoptotic factors during and after chronic nerve compression
      (CNC). Nerve function was impaired after CNC and was progressively restored after
      nerve decompression, while nerve blood flow was elevated. While the expression of
      the pro-inflammatory and pro-angiogenic cytokines IL-6, TNF-alpha and VEGF-A was
      high during and after CNC, we observed that inhibition of VEGF-A receptors
      strongly counteracted the angiogenic response induced by the ex vivo CNC.
      Activation of the pro-survival transcription factor nuclear factor-kappa B (NF
      kappaB) increased during CNC, returning to control levels after nerve
      decompression. After nerve decompression, the downregulation of Mdm2 correlated
      well with an increased expression of pro-apoptotic transcription factor p53. All
      together, we bring novel evidence that CNC activates transcription factors such
      as NF-kappaB and p53, which are key effectors of the cellular stress response,
      suggesting a neuroprotective process associated with an increased VEGF-A-mediated
      neurotrophic effect. Our results highlight the role of pro-angiogenic and pro
      inflammatory cytokines during CNC that are reinforced by increasing neurotrophic
      capacity during recovery to promote nerve regeneration.

PMID- 24865512
TI  - Interactions of oxidative stress and neurovascular inflammation in the
      pathogenesis of traumatic brain injury.
AB  - Traumatic brain injury (TBI) is a major cause of death in the young age group and
      leads to persisting neurological impairment in many of its victims. It may result
      in permanent functional deficits because of both primary and secondary damages.
      This review addresses the role of oxidative stress in TBI-mediated secondary
      damages by affecting the function of the vascular unit, changes in blood-brain
      barrier (BBB) permeability, posttraumatic edema formation, and modulation of
      various pathophysiological factors such as inflammatory factors and enzymes
      associated with trauma. Oxidative stress plays a major role in many
      pathophysiologic changes that occur after TBI. In fact, oxidative stress occurs
      when there is an impairment or inability to balance antioxidant production with
      reactive oxygen species (ROS) and reactive nitrogen species (RNS) levels. ROS
      directly downregulate proteins of tight junctions and indirectly activate matrix
      metalloproteinases (MMPs) that contribute to open the BBB. Loosening of the
      vasculature and perivascular unit by oxidative stress-induced activation of MMPs
      and fluid channel aquaporins promotes vascular or cellular fluid edema, enhances
      leakiness of the BBB, and leads to progression of neuroinflammation. Likewise,
      oxidative stress activates directly the inflammatory cytokines and growth factors
      such as IL-1beta, tumor necrosis factor-alpha (TNF-alpha), and transforming
      growth factor-beta (TGF-beta) or indirectly by activating MMPs. In another
      pathway, oxidative stress-induced degradation of endothelial vascular endothelial
      growth factor receptor-2 (VEGFR-2) by MMPs leads to a subsequent elevation of
      cellular/serum VEGF level. The decrease in VEGFR-2 with a subsequent increase in
      VEGF-A level leads to apoptosis and neuroinflammation via the activation of
      caspase-1/3 and IL-1beta release. 

PMID- 24865516
TI  - Targeting the unfolded protein response in heart diseases.
AB  - In neurological disease and diabetes, the unfolded protein response (UPR) has
      been investigated for years, while its function in heart disease is less well
      understood. All three branches of the UPR are involved in ischaemia/reperfusion
      and can either protect or impair heart function. Recently, UPR has been found to
      play a role in arrhythmogenesis during human heart failure, and blocking UPR has
      an antiarrhythmic effect. This review will discuss the rationale for and
      challenges to targeting UPR in heart disease. 

PMID- 24865518
TI  - Mutations in the palm subdomain of Twa DNA polymerase to enhance PCR efficiency
      and its function analysis.
AB  - Among the family B DNA polymerases, the Twa DNA polymerase from T. wiotapuensis,
      a hyperthermophilic archaeon, has exceedingly high fidelity. For applications in
      PCR, however, the enzyme is limited by its low extension rate and processivity.
      To resolve these weaknesses, we focused on two amino acid residues (A381 and
      N501) located at the palm subdomain of Twa DNA polymerase. Following replacement
      of these residues by site-directed mutagenesis, Twa N501R DNA polymerase showed
      significantly improved polymerase function compared to the wild-type enzyme in
      terms of processivity (3-fold), extension rate (2-fold) and PCR efficiency.
      Kinetic analysis using DNA as template revealed that the kcat value of the Twa
      N501R mutant was similar to that of wild-type, but the Km of the Twa N501R mutant
      was about 1.5-fold lower than that of the wild-type. These results suggest that a
      positive charge at residue 501 located in the forked-point does not impede
      catalytic activity of the polymerase domain but stabilizes interactions between
      the polymerase domain and the DNA template. 

PMID- 24865517
TI  - Breast cancer screening practices among first-generation immigrant muslim women.
AB  - BACKGROUND: The purpose of this study was to identify beliefs about breast
      cancer, screening practices, and factors associated with mammography use among
      first-generation immigrant Muslim women in Chicago, IL. METHODS: A convenience
      sample of 207 first-generation immigrant Muslim women (Middle Eastern 51%; South
      Asian 49%) completed a culturally adapted questionnaire developed from
      established instruments. The questionnaire was administered in Urdu, Hindi,
      Arabic, or English, based on participant preference. Internal-consistency
      reliability was demonstrated for all scales (alpha coefficients ranged from 0.64
      to 0.91). Associations between enabling, predisposing, and need variables and the
      primary outcome of mammography use were explored by fitting logistic regression
      models. RESULTS: Although 70% of the women reported having had a mammogram at
      least once, only 52% had had one within the past 2 years. Four factors were
      significant predictors of ever having had a mammogram: years in the United
      States, self-efficacy, perceived importance of mammography, and intent to be
      screened. Five factors were significant predictors of adherence (having had a
      mammogram in the past 2 years): years in the United States, having a primary care
      provider, perceived importance of mammography, barriers, and intent to be
      screened. CONCLUSIONS: This article sheds light on current screening practices
      and identifies theory-based constructs that facilitate and hinder Muslim women's
      participation in mammography screening. Our findings provide insights for
      reaching out particularly to new immigrants, developing patient education
      programs grounded in culturally appropriate approaches to address perceived
      barriers and building women's self-efficacy, as well as systems-level
      considerations for ensuring access to primary care providers.

PMID- 24865520
TI  - [Cerebral sinovenous thrombosis in children due to L-asparaginase].

PMID- 24865521
TI  - [Clavicular swelling: is it due to trauma?].

PMID- 24865523
TI  - Attenuation of mismatch negativity (MMN) and novelty P300 in schizophrenia
      patients with auditory hallucinations experiencing acute exacerbation of illness.
AB  - This study examined measures of early auditory feature analysis, including the
      mismatch negativity (MMN) and novelty P300 (NP3) in schizophrenia patients (SZ)
      with persistent auditory hallucinations (AH) during an acute psychotic episode
      requiring hospitalisation. Neuroelectric activity was recorded in 10 SZ patients
      and 13 healthy controls (HC) during a passive auditory oddball task including
      novel environmental sounds. MMN/NP3 amplitudes and latencies were compared
      between groups and were correlated with trait (PSYRATS) and state measures of AH
      severity as well as clinical symptom ratings in SZs.SZ patients (vs. HCs)
      exhibited reduced MMN amplitudes to both rare deviant and novel stimuli, as well
      as reduced NP3 amplitudes. Additionally, while novelty MMN amplitudes were
      correlated with measures of hallucinatory trait, NP3 amplitudes were correlated
      with measures of hallucinatory state. Therefore, in acutely ill SZ patients,
      individual components of the auditory novelty detection mechanism may be
      differentially sensitive to varying aspects of AHs. 

PMID- 24865526
TI  - Limited granulomatosis with polyangiitis in an adolescent with Crohn's disease on
      infliximab therapy: cause or coincidence?
AB  - Pulmonary involvement in Crohn's disease (CD) may precede the development of
      intestinal inflammation, but in most cases occurs during the course of treatment,
      either as an extra-intestinal manifestation, because of secondary infections, or
      as a side effect of the therapy itself. This case highlights the differential
      diagnosis and work up for multiple pulmonary nodules that developed in a patient
      with CD who had been in remission on infliximab therapy. Even though infectious
      causes, such as Mycobacteria and Fungi, account for majority of these cases, the
      possibility of non-infectious conditions such as autoimmune disorders should also
      be considered. 

PMID- 24865527
TI  - The putative Agrobacterium transcriptional activator-like virulence protein VirD5
      may target T-complex to prevent the degradation of coat proteins in the plant
      cell nucleus.
AB  - Agrobacterium exports at least five virulence proteins (VirE2, VirE3, VirF,
      VirD2, VirD5) into host cells and hijacks some host plant factors to facilitate
      its transformation process. Random DNA binding selection assays (RDSAs),
      electrophoretic mobility shift assays (EMSAs) and yeast one-hybrid systems were
      used to identify protein-bound DNA elements. Bimolecular fluorescence
      complementation, glutathione S-transferase pull-down and yeast two-hybrid assays
      were used to detect protein interactions. Protoplast transformation,
      coprecipitation, competitive binding and cell-free degradation assays were used
      to analyze the relationships among proteins. We found that Agrobacterium VirD5
      exhibits transcriptional activation activity in yeast, is located in the plant
      cell nucleus, and forms homodimers. A specific VirD5-bound DNA element designated
      D5RE (VirD5 response element) was identified. VirD5 interacted directly with
      Arabidopsis VirE2 Interacting Protein 1 (AtVIP1). However, the ternary complex of
      VirD5-AtVIP1-VirE2 could be detected, whereas that of VirD5-AtVIP1-VBF (AtVIP1
      Binding F-box protein) could not. We demonstrated that VirD5 competes with VBF
      for binding to AtVIP1 and stabilizes AtVIP1 and VirE2 in the cell-free
      degradation system. Our results indicated that VirD5 may act as both a
      transcriptional activator-like effector to regulate host gene expression and a
      protector preventing the coat proteins of the T-complex from being quickly
      degraded by the host's ubiquitin proteasome system (UPS). 

PMID- 24865529
TI  - Enzymatic mechanism of GPI anchor attachment clarified.

PMID- 24865525
TI  - A randomized clinical trial of self-help intervention for smoking cessation:
      research design, interventions, and baseline data.
AB  - Tobacco smoking is the leading preventable cause of mortality and morbidity.
      Although behavioral counseling combined with pharmacotherapy is the most
      effective approach to aiding smoking cessation, intensive treatments are rarely
      chosen by smokers, citing inconvenience. In contrast, minimal self-help
      interventions have the potential for greater reach, with demonstrated efficacy
      for relapse prevention, but not for smoking cessation. This paper summarizes the
      design and methods used for a randomized controlled trial to assess the efficacy
      of a minimal self-help smoking cessation intervention that consists of a set of
      booklets delivered across time. Baseline participant recruitment data are also
      presented. Daily smokers were recruited nationally via multimedia advertisements
      and randomized to one of three conditions. The Usual Care (UC) group received a
      standard smoking-cessation booklet. The Standard Repeated Mailings (SRM) group
      received 8 booklets mailed over a 12-month period. The Intensive Repeated
      Mailings (IRM) group received 10 booklets and additional supplemental materials
      mailed monthly over 18months. A total of 2641 smokers were screened, 2349 were
      randomized, and 1874 provided data for analyses. Primary outcomes will be self
      reported abstinence at 6-month intervals up to 30months. If the self-help
      booklets are efficacious, this minimal, low cost intervention can be widely
      disseminated and, hence, has the potential for significant public health impact
      with respect to reduction in smoking-related illness and mortality. 

PMID- 24865524
TI  - Alteration of miRNA activity via context-specific modifications of Argonaute
      proteins.
AB  - miRNAs are enclosed within Argonaute (Ago) proteins, the downstream effectors of
      small RNA-mediated gene silencing. Because miRNAs mediate extensive networks of
      post-transcriptional control, cells have evolved multiple strategies to control
      their activity with precision. A growing theme of recent years is how post
      translational modifications of Ago proteins, such as prolyl hydroxylation,
      phosphorylation, ubiquitination, and poly-ADP-ribosylation, alter miRNA activity
      at global or specific levels. In this review, we discuss recent advances in Ago
      modifications in mammalian cells and emphasize how such alterations modulate
      small RNA function to coordinate appropriate downstream cellular responses. These
      findings provide a framework to understand how Ago protein modifications are
      linked to reorganization of post-transcriptional regulatory networks, enabling
      dynamic responses to diverse external stimuli and changing environmental
      conditions. 

PMID- 24865530
TI  - A universal DNA extraction and PCR amplification method for fungal rDNA sequence
      based identification.
AB  - Accurate identification of fungal pathogens using a sequence-based approach
      requires an extraction method that yields template DNA pure enough for polymerase
      chain reaction (PCR) or other types of amplification. Therefore, the objective of
      this study was to develop and standardise a rapid, inexpensive DNA extraction
      protocol applicable to the major fungal phyla, which would yield sufficient
      template DNA pure enough for PCR and sequencing. A total of 519 clinical and
      culture collection strains, comprised of both yeast and filamentous fungi, were
      prepared using our extraction method to determine its applicability for PCR,
      which targeted the ITS and D1/D2 regions in a single PCR amplicon. All templates
      were successfully amplified and found to yield the correct strain identification
      when sequenced. This protocol could be completed in approximately 30 min and
      utilised a combination of physical and chemical extraction methods but did not
      require organic solvents nor ethanol precipitation. The method reduces the number
      of tube manipulations and yielded suitable template DNA for PCR amplification
      from all phyla that were tested.

PMID- 24865531
TI  - The role of nonsteroidal anti-inflammatory drugs in the prevention of post
      endoscopic retrograde cholangiopancreatography pancreatitis.
AB  - Post-ERCP pancreatitis (PEP) is the most common major complication associated
      with ERCP. Beginning with an overview of the risk factors for the development of
      PEP, this review introduces the mechanism of injury in PEP and the role of
      pharmacological prevention. NSAIDs are increasingly found to offer prevention
      against the development of PEP, and their mechanism and supportive data are
      summarized, especially in relationship to the practice of prophylactic pancreatic
      duct stenting.

PMID- 24865533
TI  - Islet cell response to high fat programming in neonate, weanling and adolescent
      Wistar rats.
AB  - CONTEXT: High fat programming, by exposure to a high saturated fat diet during
      fetal and/or lactational life induces metabolic derangements and alters islet
      cell architecture in neonate and weanling rats. OBJECTIVE: The present study
      assessed metabolic changes and islet cell dynamics in response to high fat
      maintenance during specific developmental periods in adolescent rats, with some
      parameters also studied in neonate and weanling rats. METHODS: The experimental
      groups comprised neonates, weanlings and adolescents maintained on a high fat
      diet during specific periods of fetal, lactational and/or postnatal life. Control
      neonates, weanlings and adolescents were maintained on a standard laboratory
      (control or low fat) diet. Fetal high fat programmed (i.e., maintained on a high
      fat diet exclusively during fetal life) neonates were insulin resistant. RESULTS:
      Weanlings maintained on a high fat diet throughout fetal and lactational life had
      increased pancreas weights. Fetal high fat programmed adolescents presented a
      normal phenotype mimicking the control adolescents. Adolescents maintained on a
      postnatal high fat diet had increased body weights, hyperglycemia,
      hyperinsulinemia, hyperleptinemia and insulin resistance displaying beta cell
      hypertrophy and increased islet cell proliferation. Adolescents maintained on a
      fetal and postnatal high fat diet had increased body weights, hyperleptinemia,
      hyperinsulinemia and insulin resistance. CONCLUSIONS: High fat programming
      induces various diabetogenic phenotypes which present at different life stages.
      The postnatal period from birth to adolescence represents an extension for high
      fat programming of metabolic disease.

PMID- 24865534
TI  - Severe acute pancreatitis: a possible role of intramyocardial cytokine
      production.
AB  - CONTEXT: Several mechanisms are involved in the development of the local and
      systemic response in acute pancreatitis. Cardiovascular system may be affected
      throughout the clinical course of acute pancreatitis. The aim was to evaluate
      local myocardial cytokine production, as well as, functional and histological
      myocardial alterations in severe acute pancreatitis. METHODS: The animals were
      divided into three groups: Group 1: control; Group 2: sham; Group 3: severe acute
      pancreatitis. Echocardiographic assessment of cardiac function, serum levels of
      amylase and cytokines (TNF-alpha, IL-6 and IL-10), and mRNA expression of TNF
      alpha, IL-6 and TGF-beta were measured. Myocardial tissue alterations were
      analysed by histological examination. RESULTS: The serum TNF-alpha and IL-10
      levels were significant higher in AP 2h group. The mRNA IL-6 levels from group AP
      2h were statistically higher. The mRNA TNF-alpha level from sham group and AP 2h
      were statistically lower. Significant changes in the left ventricular diameter
      were found in AP 2h and AP 12h groups. There were statistical changes for
      vacuolar degeneration, picnosis and loss of nucleus, and lymphocytes. CONCLUSION:
      We found cardiac and histological changes compatible with the inflammatory
      process triggered by SAP with the promotion of local myocardial cytokine
      production.

PMID- 24865535
TI  - No-touch pancreatectomy for invasive ductal carcinoma of the pancreas.
AB  - BACKGROUND: Pancreatectomy is the only effective treatment for cancers of the
      pancreas. Surgeons usually grasp tumors during pancreatectomy; however, this
      procedure may increase the risk of squeezing and shedding of the cancer cells
      into the portal vein, retroperitoneum, and/or peritoneal cavity. In an effort to
      overcome these problems, we have developed surgical techniques for no-touch
      pancreatectomy. METHODS: From April 2008 through September 2013, 52 patients have
      been operated on no-touch pancreatectomy for invasive ductal carcinoma of the
      pancreas by a single operator (M.H.). Among them, 40 received
      pancreatoduodenectomy (PD), and 12 did distal pancreatectomy (DP). Twenty two
      cases (42%) required SMV-PV resection. This is a study to see if pancreatectomy
      can be technically done using a no-touch surgical technique without deteriorating
      the post-operative prognosis. During the procedure, the pancreatic tumor is
      neither grasped nor squeezed by the surgeon. Furthermore, for improved dissection
      of the retroperitoneal tissue (leftward and posterior margins for PD and
      rightward and posterior margins for DP), we use a hanging and clamping maneuver
      and dissection behind Gerota fascia. RESULTS: Overall 2- and 5-year survival
      rates were 64 and 42% with mean follow-up periods of 34.4 months (range: 6-68
      months). Recurrence free 2- and 5-year survival rates were 49 and 31%,
      respectively. The 5-year survival rates of patients with JPS-stage III and those
      with JPS-stage IV were 57 and 20%, respectively. The 5-year survival rates of
      patients with UICC-stage IIA and those with UICC- stage IIB were 49 and 39%,
      respectively. Patients with UICC-stage III or IV did not survive for more than 2
      years. CONCLUSIONS: No-touch pancreatectomy has many theoretic advantages that
      merit further investigation in future randomized controlled trials.

PMID- 24865536
TI  - Tube pancreatico-duodenostomy for management of a severe penetrating
      pancreaticoduodenal injury.
AB  - CONTEXT: Optimal management of penetrating pancreaticoduodenal injuries and
      better outcomes are associated with simple, fast damage control surgery and
      shorter operative time. The performance of pyloric exclusion and tube
      duodenostomy has markedly decreased. However, there is still a trend toward their
      performance in cases of delay duodenal repair or severe pancreaticoduodenal
      injury. CASE REPORT: The present report describes a case of a hemodynamically
      stable patient with a single penetrating gunshot trauma causing an AAST-OIS grade
      III pancreatic head injury and grade IV injury of the second portion of the
      duodenum. The patient was treated in our Level IV rural trauma center and
      submitted to primary closure of the posterolateral duodenal wall (the laceration
      of the contralateral inner medial duodenal wall could not be repaired), external
      duodenal and pancreatic drainage, and duodenal decompression by tube pancreatico
      duodenostomy (insertion of a 18 Fr Foley catheter through the laceration of the
      pancreatic head toward the duodenal lumen), tube cholangiostomy, and pyloric
      exclusion accompanied with a feeding jejunostomy. CONCLUSIONS: Tube pancreatico
      duodenostomy, which is described for the first time in the literature, turned out
      to be effective and can be considered as an option in pancreaticoduodenal trauma
      when the inner medial duodenal wall cannot be repaired.

PMID- 24865537
TI  - Adrenal cavernous hemangioma: a case report with review of the literature.
AB  - CONTEXT: Adrenal cavernous hemangioma is a rare type of tumor that is usually
      diagnosed post-operatively. There have only been approximately 63 cases reported
      in the literature to date. CASE REPORT: We report a case of adrenal cavernous
      hemangioma in a 27-year-old pregnant woman. The mass was discovered on
      ultrasonography when she visited a gastroenterologist for vague epigastric
      discomfort and vomiting. The laboratory tests were within normal limits and did
      not show any features suggestive of adrenal endocrinologic dysfunction. Computed
      Tomography (CT) revealed a well-defined 7.8 * 7.8 oval mass in the right adrenal
      gland with speckled calcifications. The mass was removed by transabdominal
      laparoscopic surgery. Strong positive immunostaining for CD31 and CD34 with
      weakly positive staining for podoplanin/D2-40 confirmed the diagnosis of
      cavernous hemangioma. CONCLUSIONS: We reviewed 52 case reports of adrenal
      cavernous hemangioma in an attempt to identify tumor characteristics. More than
      half of the patients reviewed showed a heterogeneous internal structure of the
      mass with peripheral patchy enhancement on CT. They also showed focal or speckled
      calcifications either on X-ray or CT. Nevertheless, many of these characteristics
      overlap with the imaging phenotypes of other common diseases of the adrenal gland
      and therefore do not seem to provide definite evidence for differential
      diagnosis. Laparoscopic approach is a feasible and safe modality to remove
      adrenal cavernous hemangiomas because they seem to form a rigid fibrotic capsule;
      hence the risk of bleeding due to surgical manipulation is relatively low.

PMID- 24865538
TI  - An unusual complication of PEG feeding after pancreatico-gastrostomy.
AB  - CONTEXT: We describe a late complication of the pancreatico-gastrostomy (PG)
      anastomosis following pancreatico-duodenectomy (PD). CASE REPORT: A percutaneous
      endoscopic gastrostomy (PEG) feeding tube was inserted many months post
      operatively. In this patient activated pancreatic enzymes eroded the gastrostomy
      tract, resulting in pain, recurrent infection and eventual removal of the
      gastrostomy tube. CONCLUSIONS: Where surgical insertion of a feeding jejunostomy
      is not viable or deemed too high risk after Whipple or PPPD, we recommend careful
      consideration of PEG tube insertion in patients with PG reconstruction. If a PEG
      is used the prophylactic use of Lanreotide is recommended.

PMID- 24865539
TI  - Autoimmune pancreatitis presenting a short narrowing of main pancreatic duct with
      subsequent progression to diffuse pancreatic enlargement over 24 months; natural
      history of autoimmune pancreatitis.
AB  - CONTEXT: Initial pancreatogram and natural history of autoimmune pancreatitis
      (AIP) have not been clarified, and there were few recent studies concerning the
      association between AIP and intraductal papillary mucinous neoplasm (IPMN). CASE
      REPORT: We report an 81-year- old man with AIP associated with IPMN. Although the
      initial pancreatogram was normal, a short narrowing of the main pancreatic duct
      (MPD) appeared during a follow-up for IPMN after 6 months, which was highly
      suggestive of pancreatic cancer. A narrowing of the MPD extended after 15 months,
      and this progressed to diffuse narrowing of the MPD with an elevation in the
      serum IgG4 levels after 24 months. Finally, the patient was diagnosed with
      diffuse-type AIP, according to the Japanese diagnostic criteria 2011 and the
      International Consensus Diagnostic Criteria. Considering the natural history of
      AIP, this marked change of the MPD is indicative of this condition. CONCLUSION:
      We report a case of AIP presenting with a short narrowing of the MPD with
      subsequent progression to diffuse pancreatic enlargement during a follow-up for
      IPMN.

PMID- 24865541
TI  - Concurrent pancreatic head and tail arteriovenous malformations in a 40-year-old
      gentleman: the first published report.
AB  - CONTEXT: Pancreatic arteriovenous malformations (AVMs) are uncommon in the
      gastrointestinal tract. Less than 100 cases have been identified in the medical
      literature. Approximately 10% of all pancreatic AVMs are sporadic. CASE REPORT:
      Herein, we report the first documented case of sporadic concurrent pancreatic
      head and tail AVMs in a 40-year-old gentleman who presented with a 10-day history
      of epigastric pain and one episode of hematemesis. Patient denied any history of
      traumatic incidents, cigarette smoking, alcohol abuse, chronic gastric/duodenal
      ulcer, chronic pancreatitis, chronic hepatic disease, difficulty swallowing,
      respiratory compromise, or weight loss. Physical examination and laboratory
      results were unremarkable. Contrast-enhanced computed tomography scan showed two
      hypervascular masses involving the pancreatic head and tail. The celiac trunk
      angiogram showed proliferating vascular networks involving the pancreatic head
      and tail. The superior mesenteric angiogram demonstrated significant vascular
      contribution to the pancreatic head arteriovenous malformation only. Due to the
      extreme locations of pancreatic AVMs in the head and tail, surgical resection of
      both lesions (leaving behind the normal pancreatic body) was not possible.
      Instead, patient underwent intraoperative irradiation therapy (IORT). During the
      procedure, patient was surgically operated to retract healthy organs/tissues, and
      then a single concentrated dose of radiation therapy was precisely applied to
      both pancreatic head and tail AVM lesions. Patient had an uneventful
      postoperative recovery and was discharged home on the second postoperative day in
      stable condition. The patient is to be seen in clinic in a 4-month-period during
      which patient will be completing a 12-month period of postoperative IORT.
      CONCLUSION: This is the first documented case of sporadic concurrent pancreatic
      head and tail AVMs. Angiography is the gold standard diagnostic modality.

PMID- 24865540
TI  - Metastatic ampullary adenocarcinoma presenting as a hydrocele: a case report.
AB  - CONTEXT: Metastases from ampullary malignancies are common, but spread to the
      testicle and paratesticular tissue is exceedingly rare with only 2 reported cases
      in the literature. CASE REPORT: We report a case of a 70 year-old male with a
      history of ampullary adenocarcinoma status post pancreaticoduodenectomy who
      presented with a symptomatic right-sided hydrocele. Subsequent pathology revealed
      metastatic ampullary adenocarcinoma. CONCLUSIONS: Metastasis to the testicle and
      paratesticular tissue from ampullary malignancies is rare, but must be considered
      in the evaluation of scrotal masses in patients with a history of ampullary
      malignancy.

PMID- 24865542
TI  - Novel tissue harmonic imaging clearly visualizes a case of intraductal papillary
      mucinous neoplasm with mural nodules.
AB  - Tissue Harmonic Echo (THE) imaging is a sonographic technique that potentially
      provides images of higher quality than can conventional B-mode images. Potential
      advantages of THE imaging include improved resolution, improved signal-to-noise
      ratio, and reduced artifacts [1, 2]. Recently, a novel THE imaging performed
      using an EUS system with a monitor/processing unit (EU-ME2 PREMIER PLUS; Olympus
      Medical Systems, Tokyo, Japan) has been developed. Using this technology, we can
      obtain two THE mode images, namely, THE-P (penetration) and THE-R (resolution).
      The THE-P mode is suitable for middle range distance observation because it
      receives a harmonic signal whose frequency is mainly 7.5 MHz. The THE-R mode is
      suitable for close distance observation from the probe because it receives a
      harmonic signal whose frequency mainly ranges from 10 to 12 MHz. Here, we report
      a case of intraductal papillary mucinous neoplasm (IPMN) with mural nodules which
      could be clearly detected using this novel THE imaging. 

PMID- 24865543
TI  - An unusual complication of acute necrotising pancreatitis detected by endoscopic
      ultrasound.

PMID- 24865544
TI  - MM-398 achieves primary endpoint of overall survival in phase III study in
      patients with gemcitabine refractory metastatic pancreatic cancer.

PMID- 24865545
TI  - Novel Henipa-like virus, Mojiang Paramyxovirus, in rats, China, 2012.

PMID- 24865546
TI  - Fatty acid binding protein 4 expression in cerebral vascular malformations:
      implications for vascular remodelling.
AB  - AIM: Arteriovenous malformations (AVM) and cavernous malformations (CM) are the
      most commonly encountered cerebral vascular malformations, which are dynamic
      lesions with de novo growth potentials. Postnatal angiogenesis and vasculogenesis
      have been postulated to play a role in the pathogenesis of these malformations.
      Fatty acid binding protein 4 (FABP4) is an intracellular lipid chaperone, which
      is expressed in a subset of endothelial cells. FABP4 enhances the angiogenic
      responses of endothelial cells and is not expressed in normal cerebral
      vasculature. Herein, we investigated the hypothesis that FABP4 expression may be
      up-regulated in AVM and CM. METHODS: The abundance of FABP4 expression was
      analysed by immunohistochemistry on 35 paraffin-embedded AVM and CM sections.
      FABP4-expressing cells were further characterized by double immunofluorescence
      using antibodies against various cell-specific markers. RESULTS: Heterogenous
      FABP4 expression was detected in 100% AVM and 78% of CM samples. Endothelial cell
      FABP4 expression was present in 65% and 43% of AVM and CM, respectively.
      Interestingly, a population of FABP4-positive perivascular cells was detected in
      100% of AVM and 86% of CM sections examined. These cells were negative for
      markers of macrophages and smooth muscle cells, but expressed vimentin, a marker
      of mesenchymal cells, including fibroblasts. CONCLUSION: FABP4 expression is
      detected in AVM and CM in a subset of endothelial cells and some perivascular
      fibroblast-like vimentin-positive cells.

PMID- 24865547
TI  - Association of anxiety, sleepiness, and sexual dysfunction with restless legs
      syndrome in hemodialysis patients.
AB  - Restless legs syndrome (RLS) is characterized by unpleasant sensations, pain in
      the legs along with irresistible urges to move the legs when at rest. It is often
      accompanied by sleep disturbance. The purpose of this study was to assess the
      association of anxiety and sleepiness with sexual function in hemodialysis
      patients with and without RLS. Sociodemographic parameters, laboratory data of
      hemodialysis patients from three dialysis centers were collected prospectively.
      Anxiety, sleepiness, sexual function, and presence of RLS symptoms were assessed
      with standardized questionnaires as the RLS Diagnosis and Scale, Hamilton Anxiety
      Rating Scale, Epworth Sleepiness Scale (ESS), Arizona Sex Experiences Scale
      (ASEX). Univariate, regression tree method were used for statistical analysis.
      RLS was observed in 45.9% (n = 113) of hemodialysis patients (n = 246). The mean
      age of patients and duration of hemodialysis were 59.7 +/- 14.0 and 4.9 +/- 4.2
      years, respectively. The correlation between Arizona Sexual Experiences Scale
      (ASEX) and sociodemographic features was significant (P < 0.0001). Patients with
      RLS had higher scores for anxiety (9.4 +/- 7.8 with RLS and 6.8 +/- 6.0 without),
      higher ESS (ESS, 6.6 +/- 5.2 with RLS and 4.6 +/- 4.0 without), and higher ASEX
      (24.6 +/- 5.7 with RLS and 22.5 +/- 6.8 without) than did those without RLS. The
      presence of RLS symptoms in hemodialysis patients was associated with sleepiness,
      anxiety, and sexual dysfunction. A regression tree method, which is a different
      statistical method, can help physicians estimate patients ASEX, RLS, ESS, and
      anxiety scores. 

PMID- 24865550
TI  - Abstracts of the Joint Congress of European Neurology, May 28, 2014, Istanbul,
      Turkey.

PMID- 24865549
TI  - Talen-mediated girdin knockout downregulates cell proliferation, migration and
      invasion in human esophageal carcinoma ECA109 cells.
AB  - Girdin is an actin-binding Akt substrate that is involved in the regulation of
      cell migration. Accumulating evidence has revealed that girdin has regulatory
      effects on invasion and metastasis in several types of cancer. However, the role
      of girdin in esophageal squamous cell carcinomas (ESCCs) is yet to be
      investigated. In the present study, tissue microarray data revealed that among 95
      cases of ESCC, 27 cases (28.7%) exhibited a low expression of girdin, while 67
      cases (71.3%) had an enhanced expression of girdin. However, among 78 cases of
      adjacent tissues, 64 cases (82.1%) did not express girdin and 14 cases (17.9%)
      exhibited a low expression of girdin. Furthermore, the expression of girdin was
      significantly associated with the tumor stage, lymph node metastasis stage, and
      tumor, lymph node and metastasis stage. Of note, the mean survival time of girdin
      positive cases was only 30.62+/-2.99 months, while it was 53.37+/-5.02 months in
      girdin-negative cases, indicating that girdin protein expression is an
      independent prognostic factor of poor survival. Talen-mediated girdin knockout
      (KO) significantly suppressed cellular proliferation, migration and invasion in
      ESCC ECA109 cells. In conclusion, the present study suggested that girdin protein
      expression was significantly correlated with cancer progression and poor
      prognosis in ESCCs, and that girdin had a positive role in the regulation of cell
      proliferation, migration and invasion in ESCC cells. Therefore, girdin may be a
      potential candidate for the development of novel prognostic tools and therapeutic
      strategies for ESCCs. 

PMID- 24865552
TI  - Conclusive evidence of replication of a plant virus in honeybees is lacking.

PMID- 24865551
TI  - Virus-encoded microRNAs facilitate gammaherpesvirus latency and pathogenesis in
      vivo.
AB  - Gammaherpesviruses, including Epstein-Barr virus (EBV), Kaposi sarcoma-associated
      herpesvirus (KSHV, or HHV-8), and murine gammaherpesvirus 68 (MHV68, gammaHV68,
      or MuHV-4), are B cell-tropic pathogens that each encode at least 12 microRNAs
      (miRNAs). It is predicted that these regulatory RNAs facilitate infection by
      suppressing host target genes involved in a wide range of key cellular pathways.
      However, the precise contribution that gammaherpesvirus miRNAs make to viral life
      cycle and pathogenesis in vivo is unknown. MHV68 infection of mice provides a
      highly useful system to dissect the function of specific viral elements in the
      context of both asymptomatic infection and disease. Here, we report (i) analysis
      of in vitro and in vivo MHV68 miRNA expression, (ii) generation of an MHV68 miRNA
      mutant with reduced expression of all 14 pre-miRNA stem-loops, and (iii)
      comprehensive phenotypic characterization of the miRNA mutant virus in vivo. The
      profile of MHV68 miRNAs detected in infected cell lines varied with cell type and
      did not fully recapitulate the profile from cells latently infected in vivo. The
      miRNA mutant virus, MHV68.Zt6, underwent normal lytic replication in vitro and in
      vivo, demonstrating that the MHV68 miRNAs are dispensable for acute replication.
      During chronic infection, MHV68.Zt6 was attenuated for latency establishment,
      including a specific defect in memory B cells. Finally, MHV68.Zt6 displayed a
      striking attenuation in the development of lethal pneumonia in mice deficient in
      IFN-gamma. These data indicate that the MHV68 miRNAs may facilitate virus-driven
      maturation of infected B cells and implicate the miRNAs as a critical determinant
      of gammaherpesvirus-associated disease. IMPORTANCE: Gammaherpesviruses such as
      EBV and KSHV are widespread pathogens that establish lifelong infections and are
      associated with the development of numerous types of diseases, including cancer.
      Gammaherpesviruses encode many small noncoding RNAs called microRNAs (miRNAs). It
      is predicted that gammaherpesvirus miRNAs facilitate infection and disease by
      suppressing host target transcripts involved in a wide range of key cellular
      pathways; however, the precise contribution that these regulatory RNAs make to in
      vivo virus infection and pathogenesis is unknown. Here, we generated a mutated
      form of murine gammaherpesvirus (MHV68) to dissect the function of
      gammaherpesvirus miRNAs in vivo. We demonstrate that the MHV68 miRNAs were
      dispensable for short-term virus replication but were important for establishment
      of lifelong infection in the key virus reservoir of memory B cells. Moreover, the
      MHV68 miRNAs were essential for the development of virus-associated pneumonia,
      implicating them as a critical component of gammaherpesvirus-associated disease.

PMID- 24865554
TI  - IraL is an RssB anti-adaptor that stabilizes RpoS during logarithmic phase growth
      in Escherichia coli and Shigella.
AB  - RpoS (sigma(S)), the general stress response sigma factor, directs the expression
      of genes under a variety of stressful conditions. Control of the cellular
      sigma(S) concentration is critical for appropriately scaled sigma(S)-dependent
      gene expression. One way to maintain appropriate levels of sigma(S) is to
      regulate its stability. Indeed, sigma(S) degradation is catalyzed by the ClpXP
      protease and the recognition of sigma(S) by ClpXP depends on the adaptor protein
      RssB. Three anti-adaptors (IraD, IraM, and IraP) exist in Escherichia coli K-12;
      each interacts with RssB and inhibits RssB activity under different stress
      conditions, thereby stabilizing sigma(S). Unlike K-12, some E. coli isolates,
      including uropathogenic E. coli strain CFT073, show comparable cellular levels of
      sigma(S) during the logarithmic and stationary growth phases, suggesting that
      there are differences in the regulation of sigma(S) levels among E. coli strains.
      Here, we describe IraL, an RssB anti-adaptor that stabilizes sigma(S) during
      logarithmic phase growth in CFT073 and other E. coli and Shigella strains. By
      immunoblot analyses, we show that IraL affects the levels and stability of
      sigma(S) during logarithmic phase growth. By computational and PCR-based
      analyses, we reveal that iraL is found in many E. coli pathotypes but not in
      laboratory-adapted strains. Finally, by bacterial two-hybrid and copurification
      analyses, we demonstrate that IraL interacts with RssB by a mechanism distinct
      from that used by other characterized anti-adaptors. We introduce a fourth RssB
      anti-adaptor found in E. coli species and suggest that differences in the
      regulation of sigma(S) levels may contribute to host and niche specificity in
      pathogenic and nonpathogenic E. coli strains. IMPORTANCE: Bacteria must cope with
      a variety of environmental conditions in order to survive. RpoS (sigma(S)), the
      general stress response sigma factor, directs the expression of many genes under
      stressful conditions in both pathogenic and nonpathogenic Escherichia coli
      strains. The regulation of sigma(S) levels and activity allows appropriately
      scaled sigma(S)-dependent gene expression. Here, we describe IraL, an RssB anti
      adaptor that, unlike previously described anti-adaptors, stabilizes sigma(S)
      during the logarithmic growth phase in the absence of additional stress. We also
      demonstrate that iraL is found in a large number of E. coli and Shigella
      isolates. These data suggest that strains containing iraL are able to initiate
      sigma(S)-dependent gene expression under conditions under which strains without
      iraL cannot. Therefore, IraL-mediated sigma(S) stabilization may contribute to
      host and niche specificity in E. coli.

PMID- 24865553
TI  - Functional genomics with a comprehensive library of transposon mutants for the
      sulfate-reducing bacterium Desulfovibrio alaskensis G20.
AB  - The genomes of sulfate-reducing bacteria remain poorly characterized, largely due
      to a paucity of experimental data and genetic tools. To meet this challenge, we
      generated an archived library of 15,477 mapped transposon insertion mutants in
      the sulfate-reducing bacterium Desulfovibrio alaskensis G20. To demonstrate the
      utility of the individual mutants, we profiled gene expression in mutants of six
      regulatory genes and used these data, together with 1,313 high-confidence
      transcription start sites identified by tiling microarrays and transcriptome
      sequencing (5' RNA-Seq), to update the regulons of Fur and Rex and to confirm the
      predicted regulons of LysX, PhnF, PerR, and Dde_3000, a histidine kinase. In
      addition to enabling single mutant investigations, the D. alaskensis G20
      transposon mutants also contain DNA bar codes, which enables the pooling and
      analysis of mutant fitness for thousands of strains simultaneously. Using two
      pools of mutants that represent insertions in 2,369 unique protein-coding genes,
      we demonstrate that the hypothetical gene Dde_3007 is required for methionine
      biosynthesis. Using comparative genomics, we propose that Dde_3007 performs a
      missing step in methionine biosynthesis by transferring a sulfur group to O
      phosphohomoserine to form homocysteine. Additionally, we show that the entire
      choline utilization cluster is important for fitness in choline sulfate medium,
      which confirms that a functional microcompartment is required for choline
      oxidation. Finally, we demonstrate that Dde_3291, a MerR-like transcription
      factor, is a choline-dependent activator of the choline utilization cluster.
      Taken together, our data set and genetic resources provide a foundation for
      systems-level investigation of a poorly studied group of bacteria of
      environmental and industrial importance. IMPORTANCE: Sulfate-reducing bacteria
      contribute to global nutrient cycles and are a nuisance for the petroleum
      industry. Despite their environmental and industrial significance, the genomes of
      sulfate-reducing bacteria remain poorly characterized. Here, we describe a
      genetic approach to fill gaps in our knowledge of sulfate-reducing bacteria. We
      generated a large collection of archived, transposon mutants in Desulfovibrio
      alaskensis G20 and used the phenotypes of these mutant strains to infer the
      function of genes involved in gene regulation, methionine biosynthesis, and
      choline utilization. Our findings and mutant resources will enable systematic
      investigations into gene function, energy generation, stress response, and
      metabolism for this important group of bacteria.

PMID- 24865556
TI  - Microbiota-induced changes in drosophila melanogaster host gene expression and
      gut morphology.
AB  - To elucidate mechanisms underlying the complex relationships between a host and
      its microbiota, we used the genetically tractable model Drosophila melanogaster.
      Consistent with previous studies, the microbiota was simple in composition and
      diversity. However, analysis of single flies revealed high interfly variability
      that correlated with differences in feeding. To understand the effects of this
      simple and variable consortium, we compared the transcriptome of guts from
      conventionally reared flies to that for their axenically reared counterparts. Our
      analysis of two wild-type fly lines identified 121 up- and 31 downregulated
      genes. The majority of these genes were associated with immune responses, tissue
      homeostasis, gut physiology, and metabolism. By comparing the transcriptomes of
      young and old flies, we identified temporally responsive genes and showed that
      the overall impact of microbiota was greater in older flies. In addition,
      comparison of wild-type gene expression with that of an immune-deficient line
      revealed that 53% of upregulated genes exerted their effects through the immune
      deficiency (Imd) pathway. The genes included not only classic immune response
      genes but also those involved in signaling, gene expression, and metabolism,
      unveiling new and unexpected connections between immunity and other systems.
      Given these findings, we further characterized the effects of gut-associated
      microbes on gut morphology and epithelial architecture. The results showed that
      the microbiota affected gut morphology through their impacts on epithelial
      renewal rate, cellular spacing, and the composition of different cell types in
      the epithelium. Thus, while bacteria in the gut are highly variable, the
      influence of the microbiota at large has far-reaching effects on host physiology.
      IMPORTANCE: The guts of animals are in constant association with microbes, and
      these interactions are understood to have important roles in animal development
      and physiology. Yet we know little about the mechanisms underlying the
      establishment and function of these associations. Here, we used the fruit fly to
      understand how the microbiota affects host function. Importantly, we found that
      the microbiota has far-reaching effects on host physiology, ranging from immunity
      to gut structure. Our results validate the notion that important insights on
      complex host-microbe relationships can be obtained from the use of a well
      established and genetically tractable invertebrate model.

PMID- 24865555
TI  - AB5075, a Highly Virulent Isolate of Acinetobacter baumannii, as a Model Strain
      for the Evaluation of Pathogenesis and Antimicrobial Treatments.
AB  - Acinetobacter baumannii is recognized as an emerging bacterial pathogen because
      of traits such as prolonged survival in a desiccated state, effective nosocomial
      transmission, and an inherent ability to acquire antibiotic resistance genes. A
      pressing need in the field of A. baumannii research is a suitable model strain
      that is representative of current clinical isolates, is highly virulent in
      established animal models, and can be genetically manipulated. To identify a
      suitable strain, a genetically diverse set of recent U.S. military clinical
      isolates was assessed. Pulsed-field gel electrophoresis and multiplex PCR
      determined the genetic diversity of 33 A. baumannii isolates. Subsequently, five
      representative isolates were tested in murine pulmonary and Galleria mellonella
      models of infection. Infections with one strain, AB5075, were considerably more
      severe in both animal models than those with other isolates, as there was a
      significant decrease in survival rates. AB5075 also caused osteomyelitis in a rat
      open fracture model, while another isolate did not. Additionally, a Tn5
      transposon library was successfully generated in AB5075, and the insertion of
      exogenous genes into the AB5075 chromosome via Tn7 was completed, suggesting that
      this isolate may be genetically amenable for research purposes. Finally, proof-of
      concept experiments with the antibiotic rifampin showed that this strain can be
      used in animal models to assess therapies under numerous parameters, including
      survival rates and lung bacterial burden. We propose that AB5075 can serve as a
      model strain for A. baumannii pathogenesis due to its relatively recent
      isolation, multidrug resistance, reproducible virulence in animal models, and
      genetic tractability. IMPORTANCE: The incidence of A. baumannii infections has
      increased over the last decade, and unfortunately, so has antibiotic resistance
      in this bacterial species. A. baumannii is now responsible for more than 10% of
      all hospital-acquired infections in the United States and has a >50% mortality
      rate in patients with sepsis and pneumonia. Most research on the pathogenicity of
      A. baumannii focused on isolates that are not truly representative of current
      multidrug-resistant strains isolated from patients. After screening of a panel of
      isolates in different in vitro and in vivo assays, the strain AB5075 was selected
      as more suitable for research because of its antibiotic resistance profile and
      increased virulence in animal models. Moreover, AB5075 is susceptible to
      tetracycline and hygromycin, which makes it amenable to genetic manipulation.
      Taken together, these traits make AB5075 a good candidate for use in studying
      virulence and pathogenicity of this species and testing novel antimicrobials.

PMID- 24865557
TI  - Spatial-temporal survey and occupancy-abundance modeling to predict bacterial
      community dynamics in the drinking water microbiome.
AB  - Bacterial communities migrate continuously from the drinking water treatment
      plant through the drinking water distribution system and into our built
      environment. Understanding bacterial dynamics in the distribution system is
      critical to ensuring that safe drinking water is being supplied to customers. We
      present a 15-month survey of bacterial community dynamics in the drinking water
      system of Ann Arbor, MI. By sampling the water leaving the treatment plant and at
      nine points in the distribution system, we show that the bacterial community
      spatial dynamics of distance decay and dispersivity conform to the layout of the
      drinking water distribution system. However, the patterns in spatial dynamics
      were weaker than those for the temporal trends, which exhibited seasonal cycling
      correlating with temperature and source water use patterns and also demonstrated
      reproducibility on an annual time scale. The temporal trends were driven by two
      seasonal bacterial clusters consisting of multiple taxa with different networks
      of association within the larger drinking water bacterial community. Finally, we
      show that the Ann Arbor data set robustly conforms to previously described
      interspecific occupancy abundance models that link the relative abundance of a
      taxon to the frequency of its detection. Relying on these insights, we propose a
      predictive framework for microbial management in drinking water systems. Further,
      we recommend that long-term microbial observatories that collect high-resolution,
      spatially distributed, multiyear time series of community composition and
      environmental variables be established to enable the development and testing of
      the predictive framework. IMPORTANCE: Safe and regulation-compliant drinking
      water may contain up to millions of microorganisms per liter, representing
      phylogenetically diverse groups of bacteria, archaea, and eukarya that affect
      public health, water infrastructure, and the aesthetic quality of water. The
      ability to predict the dynamics of the drinking water microbiome will ensure that
      microbial contamination risks can be better managed. Through a spatial-temporal
      survey of drinking water bacterial communities, we present novel insights into
      their spatial and temporal community dynamics and recommend steps to link these
      insights in a predictive framework for microbial management of drinking water
      systems. Such a predictive framework will not only help to eliminate microbial
      risks but also help to modify existing water quality monitoring efforts and make
      them more resource efficient. Further, a predictive framework for microbial
      management will be critical if we are to fully anticipate the risks and benefits
      of the beneficial manipulation of the drinking water microbiome.

PMID- 24865558
TI  - Enhanced specialized transduction using recombineering in Mycobacterium
      tuberculosis.
AB  - G: enetic engineering has contributed greatly to our understanding of
      Mycobacterium tuberculosis biology and has facilitated antimycobacterial and
      vaccine development. However, methods to generate M. tuberculosis deletion
      mutants remain labor-intensive and relatively inefficient. Here, methods are
      described that significantly enhance the efficiency (greater than 100-fold) of
      recovering deletion mutants by the expression of mycobacteriophage recombineering
      functions during the course of infection with specialized transducing phages
      delivering allelic exchange substrates. This system has been successfully applied
      to the CDC1551 strain of M. tuberculosis, as well as to a DeltarecD mutant
      generated in the CDC1551 parental strain. The latter studies were undertaken as
      there were precedents in both the Escherichia coli literature and mycobacterial
      literature for enhancement of homologous recombination in strains lacking RecD.
      In combination, these measures yielded a dramatic increase in the recovery of
      deletion mutants and are expected to facilitate construction of a comprehensive
      library of mutants with every nonessential gene of M. tuberculosis deleted. The
      findings also open up the potential for sophisticated genetic screens, such as
      synthetic lethal analyses, which have so far not been feasible for the slow
      growing mycobacteria. IMPORTANCE: Genetic manipulation of M. tuberculosis is
      hampered by laborious and relatively inefficient methods for generating deletion
      mutant strains. The combined use of phage-based transduction and recombineering
      methods greatly enhances the efficiency by which knockout strains can be
      generated. The additional elimination of recD further enhances this efficiency.
      The methods described herein will facilitate the construction of comprehensive
      gene knockout libraries and expedite the isolation of previously difficult to
      recover mutants, promoting antimicrobial and vaccine development.

PMID- 24865560
TI  - Reply to "conclusive evidence of replication of a plant virus in honeybees is
      lacking".

PMID- 24865561
TI  - Something old, something new ....

PMID- 24865562
TI  - Comparison between a new computer program and the reference software for gray
      scale median analysis of atherosclerotic carotid plaques.
AB  - PURPOSE: To compare a new dedicated software program and Adobe Photoshop for gray
      scale median (GSM) analysis of B-mode images of carotid plaques. METHODS: A
      series of 42 carotid plaques generating >=50% diameter stenosis was evaluated by
      a single observer. The best segment for visualization of internal carotid artery
      plaque was identified on a single longitudinal view and images were recorded in
      JPEG format. Plaque analysis was performed by both programs. After normalization
      of image intensity (blood = 0, adventitial layer = 190), histograms were obtained
      after manual delineation of plaque. Results were compared with nonparametric
      Wilcoxon signed rank test and Kendall tau-b correlation analysis. RESULTS: GSM
      ranged from 00 to 100 with Adobe Photoshop and from 00 to 96 with IMTPC, with a
      high grade of similarity between image pairs, and a highly significant
      correlation (R = 0.94, p < .0001). CONCLUSIONS: IMTPC software appears suitable
      for the GSM analysis of carotid plaques.

PMID- 24865559
TI  - Peptidoglycan synthesis machinery in Agrobacterium tumefaciens during unipolar
      growth and cell division.
AB  - The synthesis of peptidoglycan (PG) in bacteria is a crucial process controlling
      cell shape and vitality. In contrast to bacteria such as Escherichia coli that
      grow by dispersed lateral insertion of PG, little is known of the processes that
      direct polar PG synthesis in other bacteria such as the Rhizobiales. To better
      understand polar growth in the Rhizobiales Agrobacterium tumefaciens, we first
      surveyed its genome to identify homologs of (~70) well-known PG synthesis
      components. Since most of the canonical cell elongation components are absent
      from A. tumefaciens, we made fluorescent protein fusions to other putative PG
      synthesis components to assay their subcellular localization patterns. The cell
      division scaffolds FtsZ and FtsA, PBP1a, and a Rhizobiales- and Rhodobacterales
      specific l,d-transpeptidase (LDT) all associate with the elongating cell pole.
      All four proteins also localize to the septum during cell division. Examination
      of the dimensions of growing cells revealed that new cell compartments gradually
      increase in width as they grow in length. This increase in cell width is
      coincident with an expanded region of LDT-mediated PG synthesis activity, as
      measured directly through incorporation of exogenous d-amino acids. Thus,
      unipolar growth in the Rhizobiales is surprisingly dynamic and represents a
      significant departure from the canonical growth mechanism of E. coli and other
      well-studied bacilli. IMPORTANCE: Many rod-shaped bacteria, including pathogens
      such as Brucella and Mycobacteriu, grow by adding new material to their cell
      poles, and yet the proteins and mechanisms contributing to this process are not
      yet well defined. The polarly growing plant pathogen Agrobacterium tumefaciens
      was used as a model bacterium to explore these polar growth mechanisms. The
      results obtained indicate that polar growth in this organism is facilitated by
      repurposed cell division components and an otherwise obscure class of alternative
      peptidoglycan transpeptidases (l,d-transpeptidases). This growth results in
      dynamically changing cell widths as the poles expand to maturity and contrasts
      with the tightly regulated cell widths characteristic of canonical rod-shaped
      growth. Furthermore, the abundance and/or activity of l,d-transpeptidases appears
      to associate with polar growth strategies, suggesting that these enzymes may
      serve as attractive targets for specifically inhibiting growth of Rhizobiales,
      Actinomycetales, and other polarly growing bacterial pathogens.

PMID- 24865565
TI  - The function of loud calls in black howler monkeys (Alouatta pigra): food, mate,
      or infant defense?
AB  - Loud calling (i.e., howling) is the single most distinctive behavioral attribute
      of the social system of howler monkeys (Alouatta spp.), yet no general consensus
      exists regarding its main function. During a 28-month study of five groups of
      black howler monkeys (Alouatta pigra) at Palenque National Park, Mexico, we
      examined whether howling mainly functioned in the defense of food resources,
      mates, or infants vulnerable to infanticide. We recorded 602 howling bouts.
      Howling occurred more frequently when monkeys were feeding, particularly on
      fruits, and less frequently when they were resting than would be expected by
      chance. Furthermore, howling was concentrated in areas of the home range in which
      major feeding sites were located. Howling did not occur more frequently when
      vulnerable infants or potentially fertile females were present versus absent, nor
      did the howling rate increase with an increasing number of vulnerable infants or
      potentially fertile females in the group. Howling bouts lasted on average 14.4 +/
      SE 0.5 min, and call duration was not influenced by the presence of vulnerable
      infants or potentially fertile females. The duration of spontaneous calls,
      however, was positively correlated to the percentage of feeding time in the
      vicinity of howling locations. In addition, vocal displays lasted longer when
      neighboring groups and extragroup males were within visual contact compared with
      spontaneous calls and calls in response to nearby calls in which there was no
      visual contact between callers. Our findings suggest that loud calls in black
      howler monkeys are multifunctional, but most frequently occur in the defense of
      major feeding sites. These calls also may function in the defense of infants and
      mates during encounters with extragroup males.

PMID- 24865566
TI  - Post-contrast myocardial T(1) and ECV disagree in a longitudinal canine study.
AB  - Both post-contrast myocardial T1 and extracellular volume (ECV) measurements have
      been associated with diffuse interstitial fibrosis. The cardiovascular magnetic
      resonance (CMR) field is migrating towards ECV, because it is largely insensitive
      to confounders that affect post-contrast myocardial T1 . Despite the theoretical
      advantages of myocardial ECV over post-contrast myocardial T1 , systematic
      experimental studies comparing the two measurements are largely lacking. We
      sought to measure the temporal changes in post-contrast myocardial T1 and ECV in
      an established canine model with chronic atrial fibrillation. Seventeen mongrel
      dogs, implanted with a pacemaker to induce chronic atrial fibrillation via rapid
      atrial pacing, were scanned multiple times for a total of 46 CMR scans at 3T.
      These dogs with different disease durations (0-22 months) were part of a separate
      longitudinal study aimed at studying the relationship between AF and
      pathophysiology. In each animal, we measured native and post-contrast T1 values
      and hematocrit. Temporal changes in post-contrast myocardial T1 and ECV, as well
      as other CMR parameters, were modeled with linear mixed effect models to account
      for repeated measurements over disease duration. In 17 animals, post-contrast
      myocardial T1 decreased significantly from 872 to 698 ms (p < 0.001), which
      corresponds to a 24.9% relative reduction. In contrast, ECV increased from 21.0
      to 22.0% (p = 0.38), which corresponds to only a 4.5% relative increase. To
      partially investigate this discrepancy, we quantified collagen volume fraction
      (CVF) in post-mortem heart tissues of six canines sacrificed at different disease
      durations (0-22 months). CVF quantified by histology increased from 0.9 to 1.9%
      (p = 0.56), which agrees better with ECV than with post-contrast myocardial T1 .
      This study shows that post-contrast myocardial T1 and ECV may disagree in a
      longitudinal canine study. A more comprehensive study, including histologic,
      cardiac, and renal functional analyses, is warranted to test rigorously which CMR
      parameter (ECV or post-contrast myocardial T1 ) agrees better with CVF.

PMID- 24865567
TI  - Intravenous magnesium sulfate for treating adults with acute asthma in the
      emergency department.
AB  - BACKGROUND: Asthma is a chronic respiratory condition characterised by airways
      inflammation, constriction of airway smooth muscle and structural alteration of
      the airways that is at least partially reversible. Exacerbations of asthma can be
      life threatening and place a significant burden on healthcare services. Various
      guidelines have been published to inform management personnel in the acute
      setting; several include the use of a single bolus of intravenous magnesium
      sulfate (IV MgSO4) in cases that do not respond to first-line treatment. However,
      the effectiveness of this approach remains unclear, particularly in less severe
      cases. OBJECTIVES: To assess the safety and efficacy of IV MgSO4 in adults
      treated for acute asthma in the emergency department. SEARCH METHODS: We
      identified trials from the Cochrane Airways Review Group Specialised Register
      (CAGR) up to 2 May 2014. We also searched www.ClinicalTrials.gov and reference
      lists of other reviews, and we contacted trial authors to ask for additional
      information. SELECTION CRITERIA: We included randomised controlled trials (RCTs)
      of adults treated in the emergency department (ED) for exacerbations of asthma if
      they compared any dose of IV MgSO4 with placebo. DATA COLLECTION AND ANALYSIS:
      All review authors screened titles and abstracts for inclusion, and at least two
      review authors independently extracted study characteristics, risk of bias and
      numerical data. Disagreements were resolved by consensus, and we contacted trial
      investigators to obtain missing information.We analysed dichotomous data as odds
      ratios using study participants as the unit of analysis, and we analysed
      continuous data as mean differences or standardised mean differences using fixed
      effect models. We rated all outcomes using GRADE and presented results in Summary
      of findings table 1.We carried out subgroup analyses on the primary outcome for
      baseline severity of exacerbations and whether or not ipratropium bromide was
      given as a co-medication. Unpublished data and studies at high risk of bias for
      blinding were removed from the main analysis in sensitivity analyses. MAIN
      RESULTS: Fourteen studies met the inclusion criteria, randomly assigning 2313
      people with acute asthma to the comparisons of interest in this review.Most
      studies were double-blinded trials comparing a single infusion of 1.2 g or 2 g IV
      MgSO4 over 15 to 30 minutes versus a matching placebo. Eleven were conducted at a
      single centre, and three were multi-centre trials. Participants in almost all of
      the studies had already been given at least oxygen, nebulised short-acting beta2
      agonists and IV corticosteroids in the ED; in some studies, investigators also
      administered ipratropium bromide. Ten studies included only adults, and four
      included both adults and children; these were included because the mean age of
      participants was over 18 years.Intravenous MgSO4 reduced hospital admissions
      compared with placebo (odds ratio (OR) 0.75, 95% confidence interval (CI) 0.60 to
      0.92; I(2) = 28%, P value 0.18; n = 972; high-quality evidence). In absolute
      terms, this odds ratio translates into a reduction of seven hospital admissions
      for every 100 adults treated with IV MgSO4 (95% CI two to 13 fewer). The test for
      subgroup differences revealed no statistical heterogeneity between the three
      severity subgroups (I(2) = 0%, P value 0.73) or between the four studies that
      administered nebulised ipratropium bromide as a co-medication and those that did
      not (I(2) = 0%, P value 0.82). Sensitivity analyses in which unpublished data and
      studies at high risk for blinding were removed from the primary analysis did not
      change conclusions.Within the secondary outcomes, high- and moderate-quality
      evidence across three spirometric indices suggests some improvement in lung
      function with IV MgSO4. No difference was found between IV MgSO4and placebo for
      most of the non-spirometric secondary outcomes, all of which were rated as low or
      moderate quality (intensive care admissions, ED treatment duration, length of
      hospital stay, readmission, respiration rate, systolic blood pressure).Adverse
      events were inconsistently reported and were not meta-analysed. The most commonly
      cited adverse events in the IV MgSO4 groups were flushing, fatigue, nausea and
      headache and hypotension (low blood pressure). AUTHORS' CONCLUSIONS: This review
      provides evidence that a single infusion of 1.2 g or 2 g IV MgSO4 over 15 to 30
      minutes reduces hospital admissions and improves lung function in adults with
      acute asthma who have not responded sufficiently to oxygen, nebulised short
      acting beta2-agonists and IV corticosteroids. Differences in the ways the trials
      were conducted made it difficult for the review authors to assess whether
      severity of the exacerbation or additional co-medications altered the treatment
      effect of IV MgSO4. Limited evidence was found for other measures of benefit and
      safety.Studies conducted in these populations should clearly define baseline
      severity parameters and systematically record adverse events. Studies recruiting
      participants with exacerbations of varying severity should consider subgrouping
      results on the basis of accepted severity classifications.

PMID- 24865568
TI  - Ribosomal s15: A novel therapeutic target for Parkinson's disease.

PMID- 24865571
TI  - Polymethylsilsesquioxane-cellulose nanofiber biocomposite aerogels with high
      thermal insulation, bendability, and superhydrophobicity.
AB  - Polymethylsilsesquioxane-cellulose nanofiber (PMSQ-CNF) composite aerogels have
      been prepared through sol-gel in a solvent containing a small amount of CNFs as
      suspension. Since these composite aerogels do not show excessive aggregation of
      PMSQ and CNF, the original PMSQ networks are not disturbed. Composite aerogels
      with low density (0.020 g cm(-3) at lowest), low thermal conductivity (15 mW m(
      1) K(-1)), visible light translucency, bending flexibility, and
      superhydrophobicity thus have been successfully obtained. In particular, the
      lowest density and bending flexibility have been achieved with the aid of the
      physical supporting effect of CNFs, and the lowest thermal conductivity is
      comparable with the original PMSQ aerogels and standard silica aerogels. The PMSQ
      CNF composite aerogels would be a candidate to practical high-performance thermal
      insulating materials. 

PMID- 24865569
TI  - Adjustment among children with relatives who participated in the manhunt
      following the Boston Marathon attack.
AB  - BACKGROUND: Following the Boston Marathon attack, the extraordinary interagency
      manhunt and shelter-in-place made for a truly unprecedented experience for area
      families. Although research on Boston youth has found robust associations between
      manhunt-related experiences and post-attack functioning, such work does little to
      identify the specific needs of a particularly vulnerable population--i.e.,
      children with a relative who participated in the manhunt. Understanding the
      adjustment of these youth is critical for informing clinical efforts. METHODS:
      Survey of Boston-area parents/caretakers (N = 460) reporting on their child's
      attack/manhunt-related experiences, as well as psychosocial functioning in the
      first six post-attack months; analyses compared youth with and without a relative
      in law enforcement or the armed services who participated in the manhunt.
      RESULTS: The proportion of youth with likely PTSD was 5.7 times higher among
      youth with relatives in the manhunt than among youth without. After accounting
      for child demographics, blast exposure, and children's own exposure to manhunt
      events (e.g., hearing/seeing gunfire/explosions, having officers enter/search
      home), having a relative in the manhunt significantly predicted child PTSD
      symptoms, emotional symptoms, and hyperactivity/inattention. Fear during the
      manhunt that a loved one could be hurt mediated relationships between having a
      relative in the manhunt and clinical outcomes; living within the zone of greatest
      manhunt activity did not moderate observed relationships. CONCLUSIONS: Children
      with relatives called upon to participate in the unprecedented interagency
      manhunt following the Boston Marathon attack carried a particularly heavy mental
      health burden. Continued research is needed to clarify the clinical needs of
      youth with relatives in high-risk occupations.

PMID- 24865575
TI  - Palladium-catalyzed aerobic oxidative allylic C-H arylation of alkenes with
      polyfluorobenzenes.
AB  - An aerobic oxidative cross-coupling reaction of alkenes with polyfluorobenzenes,
      through palladium-catalyzed allylic C-H activation, is reported. This attractive
      route provides a new way to forge allylic C-C bonds of valuable products, in good
      yields, with high regioselectivity. 

PMID- 24865572
TI  - Dicationic imidazolium ionic liquid modified silica as a novel reversed
      phase/anion-exchange mixed-mode stationary phase for high-performance liquid
      chromatography.
AB  - A dicationic imidazolium ionic liquid modified silica stationary phase was
      prepared and evaluated by reversed-phase/anion-exchange mixed-mode
      chromatography. Model compounds (polycyclic aromatic hydrocarbons and anilines)
      were separated well on the column by reversed-phase chromatography; inorganic
      anions (bromate, bromide, nitrate, iodide, and thiocyanate), and organic anions
      (p-aminobenzoic acid, p-anilinesulfonic acid, sodium benzoate, pathalic acid, and
      salicylic acid) were also separated individually by anion-exchange
      chromatography. Based on the multiple sites of the stationary phase, the column
      could separate 14 solutes containing the above series of analytes in one run. The
      dicationic imidazolium ionic liquid modified silica can interact with hydrophobic
      analytes by the hydrophobic C6 chain; it can enhance selectivity to aromatic
      compounds by imidazolium groups; and it also provided anion-exchange and
      electrostatic interactions with ionic solutes. Compared with a monocationic ionic
      liquid functionalized stationary phase, the new stationary phase represented
      enhanced selectivity owing to more interaction sites. 

PMID- 24865570
TI  - Effect of feedback during virtual training of grip force control with a
      myoelectric prosthesis.
AB  - The aim of this study was to determine whether virtual training improves grip
      force control in prosthesis use, and to examine which type of augmented feedback
      facilitates its learning most. Thirty-two able-bodied participants trained grip
      force with a virtual ball-throwing game for five sessions in a two-week period,
      using a myoelectric simulator. They received either feedback on movement outcome
      or on movement execution. Sixteen controls received training that did not focus
      on force control. Variability over learning was examined with the Tolerance-Noise
      Covariation approach, and the transfer of grip force control was assessed in five
      test-tasks that assessed different aspects of force control in a pretest, a
      posttest and a retention test. During training performance increased while the
      variability in performance was decreased, mainly by reduction in noise. Grip
      force control only improved in the test-tasks that provided information on
      performance. Starting the training with a task that required low force production
      showed no transfer of the learned grip force. Feedback on movement execution was
      detrimental to grip force control, whereas feedback on movement outcome enhanced
      transfer of grip force control to tasks other than trained. Clinical implications
      of these results regarding virtual training of grip force control are discussed. 

PMID- 24865576
TI  - A meta-analysis of gender stereotypes and bias in experimental simulations of
      employment decision making.
AB  - Gender bias continues to be a concern in many work settings, leading researchers
      to identify factors that influence workplace decisions. In this study we examine
      several of these factors, using an organizing framework of sex distribution
      within jobs (including male- and female-dominated jobs as well as sex-balanced,
      or integrated, jobs). We conducted random effects meta-analyses including 136
      independent effect sizes from experimental studies (N = 22,348) and examined the
      effects of decision-maker gender, amount and content of information available to
      the decision maker, type of evaluation, and motivation to make careful decisions
      on gender bias in organizational decisions. We also examined study
      characteristics such as type of participant, publication year, and study design.
      Our findings revealed that men were preferred for male-dominated jobs (i.e.,
      gender-role congruity bias), whereas no strong preference for either gender was
      found for female-dominated or integrated jobs. Second, male raters exhibited
      greater gender-role congruity bias than did female raters for male-dominated
      jobs. Third, gender-role congruity bias did not consistently decrease when
      decision makers were provided with additional information about those they were
      rating, but gender-role congruity bias was reduced when information clearly
      indicated high competence of those being evaluated. Fourth, gender-role congruity
      bias did not differ between decisions that required comparisons among ratees and
      decisions made about individual ratees. Fifth, decision makers who were motivated
      to make careful decisions tended to exhibit less gender-role congruity bias for
      male-dominated jobs. Finally, for male-dominated jobs, experienced professionals
      showed smaller gender-role congruity bias than did undergraduates or working
      adults.

PMID- 24865577
TI  - The slippery slope: how small ethical transgressions pave the way for larger
      future transgressions.
AB  - Many recent corporate scandals have been described as resulting from a slippery
      slope in which a series of small infractions gradually increased over time (e.g.,
      McLean & Elkind, 2003). However, behavioral ethics research has rarely considered
      how unethical behavior unfolds over time. In this study, we draw on theories of
      self-regulation to examine whether individuals engage in a slippery slope of
      increasingly unethical behavior. First, we extend Bandura's (1991, 1999) social
      cognitive theory by demonstrating how the mechanism of moral disengagement can
      reduce ethicality over a series of gradually increasing indiscretions. Second, we
      draw from recent research connecting regulatory focus theory and behavioral
      ethics (Gino & Margolis, 2011) to demonstrate that inducing a prevention focus
      moderates this mediated relationship by reducing one's propensity to slide down
      the slippery slope. We find support for the developed model across 4 multiround
      studies.

PMID- 24865578
TI  - A meta-analysis of the relationship between individual assessments and job
      performance.
AB  - Though individual assessments are widely used in selection settings, very little
      research exists to support their criterion-related validity. A random-effects
      meta-analysis was conducted of 39 individual assessment validation studies. For
      the current research, individual assessments were defined as any employee
      selection procedure that involved (a) multiple assessment methods, (b)
      administered to an individual examinee, and (c) relying on assessor judgment to
      integrate the information into an overall evaluation of the candidate's
      suitability for a job. Assessor recommendations were found to be useful
      predictors of job performance, although the level of validity varied considerably
      across studies. Validity tended to be higher for managerial than nonmanagerial
      occupations and for assessments that included a cognitive ability test. Validity
      was not moderated by the degree of standardization of the assessment content or
      by use of multiple assessors for each candidate. However, higher validities were
      found when the same assessor was used across all candidates than when different
      assessors evaluated different candidates. These results should be interpreted
      with caution, given a small number of studies for many of the moderator subgroups
      as well as considerable evidence of publication bias. These limitations of the
      available research base highlight the need for additional empirical work to
      inform individual assessment practices. (PsycINFO Database Record (c) 2015 APA,
      all rights reserved). 

PMID- 24865579
TI  - The role of team goal monitoring in the curvilinear relationship between team
      efficacy and team performance.
AB  - In this research, we apply a team self-regulatory perspective to build and test
      theory focusing on the relationships between team efficacy and 2 key team
      performance criteria: a performance behavior (i.e., team effort) and a
      performance outcome (i.e., objective team sales). We theorize that rather than
      having a linear association, the performance benefits of team efficacy reach a
      point of inflection, reflective of too much of a good thing. Further, in an
      effort to establish a boundary condition of the inverted-U shaped relationship we
      predict, we also test the moderating role played by team goal monitoring in the
      nonmonotonic relationship between team efficacy and team performance. The results
      from a lagged field test, in which we collect multisource data from 153
      technology sales teams, reveal a significant curvilinear association that is
      moderated by team goal monitoring behavior. Implications for theory and practice
      are discussed.

PMID- 24865581
TI  - Mass loading and removal of select illicit drugs in two wastewater treatment
      plants in New York State and estimation of illicit drug usage in communities
      through wastewater analysis.
AB  - Sewage epidemiology is a rapidly expanding field that can provide information on
      illicit drug usage in communities, based on the measured concentrations in
      samples from wastewater treatment plants (WWTPs). In this study, select illicit
      drugs (six drugs and eight metabolites) were determined on a daily basis for a
      week in wastewater, suspended particulate matter (SPM), and sludge from two WWTPs
      in the Albany area in New York State. The WWTP that served a larger population
      (~100 000, with a flow rate of 83 300 m(3)/d) showed 3.2 (methadone) to 51 (3,4
      methylenedioxyamphetamine; MDA) times higher mass flows of illicit drugs than did
      the WWTP that served a smaller population (~15 000, with a flow rate of 6850
      m(3)/d). The consumption rate of target illicit drugs in the communities served
      by the two WWTPs was estimated to range from 1.67 to 3510 mg/d/1000 people.
      Between the dissolved and particulate phases, the fraction of methadone, 2
      ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), amphetamine, and MDA
      sorbed to SPM ranged from 34.3% to 41.1% of the total mass in the waste stream.
      The removal efficiencies of illicit drugs from the two WWTPs ranged from 4%
      (norcocaine) to 99% (cocaine); however, methamphetamine, methadone, and EDDP
      showed a negative removal in WWTPs. The environmental emission of illicit drugs
      from WWTP discharges was calculated to range from 0.38 (MDEA) to 67.5 (EDDP)
      mg/d/1000 people. Other markers such as caffeine, paraxanthine, nicotine, and
      cotinine were found to predict the concentrations of select illicit drugs in raw
      wastewater (r(2) = 0.20-0.79; p <= 0.029). 

PMID- 24865584
TI  - Evaluation of the impact of a simple hand-washing and water-treatment
      intervention in rural health facilities on hygiene knowledge and reported
      behaviours of health workers and their clients, Nyanza Province, Kenya, 2008.
AB  - Many clinics in rural western Kenya lack access to safe water and hand-washing
      facilities. To address this problem, in 2005 a programme was initiated to install
      water stations for hand washing and drinking water in 109 health facilities,
      train health workers on water treatment and hygiene, and motivate clients to
      adopt these practices. In 2008, we evaluated this intervention's impact by
      conducting observations at facilities, and interviewing staff and clients about
      water treatment and hygiene. Of 30 randomly selected facilities, 97% had water
      stations in use. Chlorine residuals were detectable in at least one container at
      59% of facilities. Of 164 interviewed staff, 79% knew the recommended water
      treatment procedure. Of 298 clients, 45% had received training on water treatment
      at a facility; of these, 68% knew the recommended water-treatment procedure. Use
      of water stations, water treatment, and client training were sustained in some
      facilities for up to 3 years.

PMID- 24865582
TI  - Upregulation of miR-21 in cisplatin resistant ovarian cancer via JNK-1/c-Jun
      pathway.
AB  - Cisplatin has been the most accepted drug for the treatment of ovarian cancer for
      almost 40 years. Although the majority of patients with ovarian cancer respond to
      front-line platinum combination chemotherapy, many patients will develop
      cisplatin-resistance disease, which is extremely rapid and fatal. Although
      various mechanisms of cisplatin resistance have been postulated, the key
      molecules involved in such resistance have not been identified. MiRNAs are
      endogenously expressed small non-coding RNAs, which are evolutionarily conserved
      and function as post-transcriptional regulators of gene expression. Dysregulation
      of miRNAs have been associated with cancer initiation, progression and drug
      resistance. The oncogenic miRNA-21, one of the best-studied miRNAs, is
      upregulated in almost all human cancers. However, the regulation of miR-21 in
      cisplatin resistant ovarian cancer cells has not been assessed. In this study, we
      measured the miR-21 expression by real-time PCR and found upregulation of miR-21
      in cisplatin resistant compared with cisplatin sensitive ovarian cancer cells.
      Chromatin immunoprecipitation studies demonstrated the association of the c-Jun
      transcription factor to the pri-mir-21 DNA promoter regions. Blocking the JNK-1,
      the major activator of c-Jun phosphorylation, reduced the expression of pre-mir
      21 and increased the expression of its well-known target gene, PDCD4.
      Overexpression of miR-21 in cisplatin sensitive cells decreased PDCD4 levels and
      increased cell proliferation. Finally, targeting miR-21 reduced cell growth,
      proliferation and invasion of cisplatin resistant ovarian cancer cells. These
      results suggest that the JNK-1/c-Jun/miR-21 pathway contributes to the cisplatin
      resistance of ovarian cancer cells and demonstrated that miR-21 is a plausible
      target to overcome cisplatin resistance. 

PMID- 24865585
TI  - Imaging of intracellular metal partitioning in marine diatoms exposed to metal
      pollution: consequences to cellular toxicity and metal fate in the environment.
AB  - This study investigates the metal content and compartmentalization changes in
      whole cells of diatom Coscinodiscus eccentricus exposed to metal overload,
      examining consequences to cellular toxicity, tolerance mechanisms, and metal fate
      in the environment. Cells exposed to Ni, Cu and Zn were analysed using nuclear
      microprobe techniques. Particle induced X-ray emission (PIXE), Rutherford
      backscattering spectrometry (RBS), and scanning transmission ion microscopy
      (STIM) were used simultaneously to obtain high-resolution imaging of
      morphological and quantitative elemental distribution data. Elemental
      partitioning within cell compartments, such as cell wall, cytoplasm and major
      organelles, was assessed. Diatoms clearly responded to excess metal levels, by
      changing cytoplasm morphology, concentrating added metals, and altering Fe
      transport mechanisms. Different metal accumulation patterns indicated high
      susceptibility to Cu, retained in the cytoplasm, and detoxification capability
      for Ni and Zn, mobilized to the vacuole. Iron and Zn were accumulated in the
      siliceous wall. Different metal distributions within the cell imply distinct
      environmental fates, Cu and Ni remain available with potential for
      biomagnification through the food web, whereas Fe and Zn are deposited at the
      bottom through frustule sedimentation. 

PMID- 24865586
TI  - Language impairment and early social competence in preschoolers with autism
      spectrum disorders: a comparison of DSM-5 profiles.
AB  - Children with autism spectrum disorder (ASD) and structural language impairment
      (LI) may be at risk of more adverse social-developmental outcomes. We examined
      trajectories of early social competence (using the Vineland-II) in 330 children
      aged 2-4 years recently diagnosed with ASD, and compared 3 subgroups classified
      by: language impairment (ASD/LI); intellectual disability (ASD/ID) and ASD
      without LI or ID (ASD/alone). Children with ASD/LI were significantly more
      socially impaired at baseline than the ASD/alone subgroup, and less impaired than
      those with ASD/ID. Growth in social competence was significantly slower for the
      ASD/ID group. Many preschool-aged children with ASD/LI at time of diagnosis
      resembled "late talkers" who appeared to catch up linguistically. Children with
      ASD/ID were more severely impaired and continued to lag further behind.

PMID- 24865589
TI  - [98th Annual Conference of the German Society for Pathology : Berlin, 12-15 June
      2014].

PMID- 24865591
TI  - Electrochemically grown nanoporous MnO2 nanowalls on a porous carbon substrate
      with enhanced capacitance through faster ionic and electrical mobility.
AB  - We report the deposition of uniform porous MnO2 nanowalls on a conducting carbon
      fiber substrate using a simple electrochemical method, which produces ordered
      nano-channels demarcated by the MnO2 walls for easy ion transport and a
      continuous electron path created by the carbon backbone. The system achieves a
      specific capacitance of 1149 F g(-1) and retains 565 F g(-1) even at dragging
      conditions as high as 100 A g(-1). 

PMID- 24865588
TI  - Diisopropylamine dichloroacetate, a novel pyruvate dehydrogenase kinase 4
      inhibitor, as a potential therapeutic agent for metabolic disorders and
      multiorgan failure in severe influenza.
AB  - Severe influenza is characterized by cytokine storm and multiorgan failure with
      metabolic energy disorders and vascular hyperpermeability. In the regulation of
      energy homeostasis, the pyruvate dehydrogenase (PDH) complex plays an important
      role by catalyzing oxidative decarboxylation of pyruvate, linking glycolysis to
      the tricarboxylic acid cycle and fatty acid synthesis, and thus its activity is
      linked to energy homeostasis. The present study tested the effects of
      diisopropylamine dichloroacetate (DADA), a new PDH kinase 4 (PDK4) inhibitor, in
      mice with severe influenza. Infection of mice with influenza A PR/8/34(H1N1)
      virus resulted in marked down-regulation of PDH activity and ATP level, with
      selective up-regulation of PDK4 in the skeletal muscles, heart, liver and lungs.
      Oral administration of DADA at 12-h intervals for 14 days starting immediately
      after infection significantly restored PDH activity and ATP level in various
      organs, and ameliorated disorders of glucose and lipid metabolism in the blood,
      together with marked improvement of survival and suppression of cytokine storm,
      trypsin up-regulation and viral replication. These results indicate that through
      PDK4 inhibition, DADA effectively suppresses the host metabolic disorder-cytokine
      cycle, which is closely linked to the influenza virus-cytokine-trypsin cycle,
      resulting in prevention of multiorgan failure in severe influenza. 

PMID- 24865590
TI  - Curcumin- and natural extract-loaded nanofibres for potential treatment of lung
      and breast cancer: in vitro efficacy evaluation.
AB  - Drug-eluting medical implants are more common, particularly for fighting against
      cancers. FDA and other drug regulatory bodies have approved many nanoformulated
      devices eluting active pharmaceutical ingredients and thus there is growing
      demand for further value- added devices. Nanofibre membranes are known for its
      versatility of drug incorporation and sustained drug release. We intend to
      fabricate natural ingredient or extract, and their combination loaded
      polycaprolactone (PCL) nanofibre for usage as drug-eluting stents or implants for
      anticancer activity against lung and breast cancers. The fabricated nanofibre
      membranes were characterised by scanning electron microscope for morphology, FT
      IR for chemical nature and tensile testing for mechanical strengths. Release of
      curcumin was studied with time to find the applicability of the device as drug
      eluting implant. The activity of the nanofibre membranes was tested against human
      breast cancer (MCF7) and lung cancer (A459) cell lines in vitro. In both the cell
      lines tested, 1% aloe vera and 5% curcumin-loaded PCL nanofibre exhibited 15%
      more cytotoxicity in comparison with the commercial drug 1% cis-Platin-loaded PCL
      nanofibre after 24 h incubation.

PMID- 24865592
TI  - Effect of dexamethasone on the incidence of post-dural puncture headache after
      spinal anesthesia: a randomized, double-blind, placebo-controlled trial and a
      meta-analysis.
AB  - The effect of dexamethasone on post-dural puncture headache (PDPH) after spinal
      anesthesia has not been well elucidated. This randomized, double-blind, placebo
      controlled trial was carried out in patients undergoing a cesarean at the Qilu
      Hospital, Shandong University. The subjects were randomly divided into a placebo
      and a dexamethasone group. The incidences of PDPH on the first, second, third and
      seventh postoperative day were studied, and the severity of PDPH was assessed
      using a visual analog scale. Studies in PubMed, Embase and the Cochrane Library
      database were searched and included in the present meta-analysis. Summary
      estimates of weighted mean differences and 95 % confidence intervals (CIs) were
      obtained using random-effects models. We included 307 participants in the
      dexamethasone group and 309 in the placebo group for analysis. The results
      indicated that prophylactic administration of 8 mg dexamethasone did not have any
      protective effect against PDPH (31 vs. 18, P = 0.054) and even increased the
      incidence of PDPH in the first 24 h in parturient patients (25 vs. 11, P =
      0.016). Furthermore, the meta-analysis also showed that dexamethasone did not
      prevent the incidence of PDPH in the postoperative follow-up days (RR 1.05; 95 %
      CI 0.46-2.38; P = 0.91) and may even have increased the trend in the first 24 h.
      Prophylactic administration of 8 mg dexamethasone does not have any protective
      effect against PDPH and may even increase the incidence of PDPH in the first 24 h
      in patients with spinal anesthesia.

PMID- 24865594
TI  - Effects of xenon insertion into hydrogen bromide. Comparison of the electronic
      structure of the HBr...CO2 and HXeBr...CO2 complexes using quantum chemical
      topology methods: electron localization function, atoms in molecules and symmetry
      adapted perturbation theory.
AB  - Quantum chemistry methods have been applied to study the influence of the Xe atom
      inserted into the hydrogen-bromine bond (HBr -> HXeBr), particularly on the
      nature of atomic interactions in the HBr...CO2 and HXeBr...CO2 complexes.
      Detailed analysis of the nature of chemical bonds has been carried out using
      topological analysis of the electron localization function, while topological
      analysis of electron density was used to gain insight into the nature of weak
      nonbonding interactions. Symmetry-adapted perturbation theory within the orbital
      approach was applied for greater understanding of the physical contributions to
      the total interaction energy. 

PMID- 24865595
TI  - Methods for managing and analyzing electronic medical records: a formative
      examination of a hospital-congregation-based intervention.
AB  - Electronic medical records (EMRs) can be a valuable tool in evaluating
      interventions involving faith-based institutions. Working with EMRs is complex.
      Methodological designs that can be used by public health and health
      administrators to assess the effectiveness of interventions are lacking. The
      study team conducted a formative evaluation of the Congregational Health Network
      (CHN) using propensity matching and Cox proportional hazard models to examine
      health outcomes and readmission rates. Along with CHN's relevance in addressing
      the needs of the most vulnerable population, factors are discussed that must be
      taken into consideration when designing such methodologies as well as limitations
      that merit attention from public health researchers and hospital administrators
      interested in conducting a formative evaluation using existing data to track the
      effectiveness of an intervention.

PMID- 24865593
TI  - Schizophrenia-risk variant rs6994992 in the neuregulin-1 gene on brain
      developmental trajectories in typically developing children.
AB  - The neuregulin-1 (NRG1) gene is one of the best-validated risk genes for
      schizophrenia, and psychotic and bipolar disorders. The rs6994992 variant in the
      NRG1 promoter (SNP8NRG243177) is associated with altered frontal and temporal
      brain macrostructures and/or altered white matter density and integrity in
      schizophrenic adults, as well as healthy adults and neonates. However, the ages
      when these changes begin and whether neuroimaging phenotypes are associated with
      cognitive performance are not fully understood. Therefore, we investigated the
      association of the rs6994992 variant on developmental trajectories of brain macro
      and microstructures, and their relationship with cognitive performance. A total
      of 972 healthy children aged 3-20 years had the genotype available for the NRG1
      rs6994992 variant, and were evaluated with magnetic resonance imaging (MRI) and
      neuropsychological tests. Age-by-NRG1-rs6994992 interactions and genotype effects
      were assessed using a general additive model regression methodology, covaried for
      scanner type, socioeconomic status, sex and genetic ancestry factors. Compared
      with the C-carriers, children with the TT-risk-alleles had subtle microscopic and
      macroscopic changes in brain development that emerge or reverse during
      adolescence, a period when many psychiatric disorders are manifested. TT-children
      at late adolescence showed a lower age-dependent forniceal volume and lower
      fractional anisotropy; however, both measures were associated with better
      episodic memory performance. To our knowledge, we provide the first multimodal
      imaging evidence that genetic variation in NRG1 is associated with age-related
      changes on brain development during typical childhood and adolescence, and
      delineated the altered patterns of development in multiple brain regions in
      children with the T-risk allele(s). 

PMID- 24865596
TI  - Immediate and long-term high levels of plasma homocysteine after extracorporeal
      shock wave lithotripsy in patients with renal stone disease.
AB  - BACKGROUND: Plasma homocysteine levels increase in patients with chronic renal
      failure. Numerous studies have demonstrated that kidney function is one of the
      most important determinants of plasma total homocysteine (tHcy) concentration. In
      this study we aimed to evaluate the relationship between tHcy levels and
      extracorporeal shock wave lithotripsy (ESWL) for patients with renal stones and
      to see if the change in homocysteine levels continued if renal dysfunction
      improved. MATERIALS AND METHODS: The study consisted of 20 patients who underwent
      first-time ESWL for renal stones. Every patient gave 3 blood samples at 24 h
      before surgery and at 2 days and at 3 months after ESWL for measurement of plasma
      levels of tHcy, creatinine, vitamin B6, and vitamin B12. RESULTS: The 20 patients
      (12 male, 8 female) had a mean age of 42.8 +/- 11.7 years. tHcy levels showed a
      statistically significant increase from 9.4 +/- 1.4 to 18 +/- 4.8 and 11.2 +/-
      2.1 at 2 days and at 3 months, respectively. Serum creatinine also showed a
      statistically significant increase compared to baseline at 2 days and at 3 months
      after ESWL. CONCLUSION: After first-time ESWL, the increase in serum levels of
      creatinine and tHcy due to renal injury, such as ischemia/reperfusion injury, may
      be severe and continue for a long period, such as 3 months. According to baseline
      levels, the increase in homocysteine levels as an indicator of oxidant stress was
      more severe than the creatinine levels after ESWL for renal stones. Our patients
      were first-time ESWL patients; however, in patients who undergo EWSL more than
      once long-term high tHcy levels should also be considered as renal.

PMID- 24865597
TI  - The problems that exist when considering the anatomic variability between the
      channels that permit interventricular shunting.
AB  - Although steps are being taken to produce a universally acceptable coding system
      for categorisation of the congenitally malformed hearts, obstacles remain in the
      search for consensus. One of the groups of lesions continuing to produce the
      greatest problems is those that permit interventricular shunting. The
      difficulties relate partly to the words used to describe the group itself, as
      those using Germanic languages describe the holes as ventricular septal defects,
      whereas those using Romance languages consider them to represent interventricular
      communications. The two terms, however, are not necessarily synonymous. Further
      disagreements relate to whether the lesions placed within the group should be sub
      categorised on the basis of their geographical location within the ventricular
      mass, as opposed to the anatomic nature of their borders. In reality, attention
      to both the features is necessary if we are to recognise the full extent of
      phenotypic variability. In this review, we first review the evolution and
      theories of analysis naming the channels that permit interventricular shunting.
      We then demonstrate that embryologic techniques provide evidence that the
      changing morphology of the developing murine heart parallels the anatomy of the
      different lesions encountered in the congenitally malformed human heart. We
      suggest that, with attention paid to the temporal development of the normal
      murine heart, combined with a strict definition of the plane of separation
      between the right and left ventricular cavities, it will be feasible to produce a
      categorisation that is acceptable to all.

PMID- 24865598
TI  - Increased levels of FFA during passive heat loading after a 2-week repeated heat
      load in Koreans.
AB  - The purpose of this study was to determine whether repeated heat load is closely
      related to circulating levels of free fatty acids (FFA) during repeated passive
      heat loading (PHL), defined as immersion of the lower body up to an umbilical
      level in hot water, 42 +/- 0.5  degrees C (three times/week, 30 min/day) for 2
      weeks. There were significant correlations between mean body temperature and FFA
      before and after repeated heat load (p < 0.001, respectively), and the level of
      FFA was significantly higher after repeated heat load during PHL (p < 0.01). The
      threshold of mean body temperature for lipolysis was lowered by repeated heat
      load and enhanced lipolysis during PHL. However, caution is needed for diabetic
      individuals.

PMID- 24865600
TI  - Screening for lung cancer using low dose computed tomography.
AB  - Screening for lung cancer with low dose computed tomography can reduce mortality
      from the disease by 20% in high risk smokers. This review covers the state of the
      art knowledge on several aspects of implementing a screening program. The most
      important are to identify people who are at high enough risk to warrant screening
      and the appropriate management of lung nodules found at screening. An accurate
      risk prediction model is more efficient than age and pack years of smoking alone
      at identifying those who will develop lung cancer and die from the disease.
      Algorithms are available for assessing people who screen positive to determine
      who needs additional imaging or invasive investigations. Concerns about low dose
      computed tomography screening include false positive results, overdiagnosis,
      radiation exposure, and costs. Further work is needed to define the frequency and
      duration of screening and to refine risk prediction models so that they can be
      used to assess the risk of lung cancer in special populations. Another important
      area is the use of computer vision software tools to facilitate high throughput
      interpretation of low dose computed tomography images so that costs can be
      reduced and the consistency of scan interpretation can be improved. Sufficient
      data are available to support the implementation of screening programs at the
      population level in stages that can be expanded when found to perform well to
      improve the outcome of patients with lung cancer. 

PMID- 24865599
TI  - Psychosocial burdens negatively impact HIV antiretroviral adherence in gay,
      bisexual, and other men who have sex with men aged 50 and older.
AB  - We sought to characterize HIV antiretroviral therapy (ART) adherence and
      psychosocial correlates of adherence in a sample of gay, bisexual, and other non
      gay or -bisexual identified men who have sex with men aged 50 and over. As part
      of a cross-sectional study we recruited a community-based sample of 199 men and
      assessed adherence to current ART medications along four domains: (1) missing
      doses in the past 4 days, (2) taking doses on the specified schedule in the past
      4 days, (3) following instructions about how to take the medications (e.g., to
      take medications with food), and (4) missing doses in the last weekend. A total
      adherence score was also computed. Bivariable analyses indicated negative
      associations between depression, sexual compulsivity, and HIV-related stigma with
      each of the individual adherence variables and the composite adherence score,
      while an older age was found to be protective. In multivariable analyses,
      controlling for age and educational attainment, a higher likelihood of missing
      doses and failing to follow instructions were related to higher levels of HIV
      related stigma, while dosing off-schedule and missing doses on weekends was
      associated with higher levels of sexual compulsivity. These results indicate that
      psychosocial burdens undermine the adherence behaviors of older HIV-positive
      sexual minority men. Programming and services to address this compromising health
      behavior must embrace a holistic approach to health as informed by syndemics
      theory, while attending to the developmental and age-specific needs of older men.

PMID- 24865602
TI  - Testing for reproductive interference in the population dynamics of two
      congeneric species of herbivorous mites.
AB  - When phylogenetically close, two competing species may reproductively interfere,
      and thereby affect their population dynamics. We tested for reproductive
      interference (RI) between two congeneric haplo-diploid spider mites, Tetranychus
      evansi and Tetranychus urticae, by investigating their interspecific mating and
      their population dynamics when they competed on the same plants. They are both
      pests of tomato, but differ in the host plant defences that they suppress or
      induce. To reduce the effect of plant-mediated interaction, we used a mutant
      tomato plant lacking jasmonate-mediated anti-herbivore defences in the
      competition experiment. In addition, to manipulate the effect of RI, we
      introduced founder females already mated with conspecific males in mild RI
      treatments or founder, virgin females in strong RI treatments (in either case
      together with heterospecific and conspecific males). As females show first-male
      sperm precedence, RI should occur especially in the founder generation under
      strong RI treatments. We found that T. urticae outcompeted T. evansi in mild, but
      not in strong RI treatments. Thus, T. evansi interfered reproductively with T.
      urticae. This result was supported by crossing experiments showing frequent
      interspecific copulations, strong postmating reproductive isolation and a
      preference of T. evansi males to mate with T. urticae (instead of conspecific)
      females, whereas T. urticae males preferred conspecific females. We conclude that
      interspecific mating comes at a cost due to asymmetric mate preferences of males.
      Because RI by T. evansi can improve its competitiveness to T. urticae, we propose
      that RI partly explains why T. evansi became invasive in Europe where T. urticae
      is endemic.

PMID- 24865603
TI  - Synthesis of novel lipophilic N-substituted norcantharimide derivatives and
      evaluation of their anticancer activities.
AB  - This research attempted to study the effect of lipophilicity on the anticancer
      activity of N-substituted norcantharimide derivatives. Twenty-three compounds
      were synthesized and their cytotoxicities against five human cancer cell lines
      studied. The lipophilicity of each derivative was altered by its substituent, an
      alkyl, alkyloxy, terpenyl or terpenyloxy group at the N-position of
      norcantharimide. Further, among all synthesized derivatives studied, the
      compounds N-farnesyloxy-7-oxabicyclo[2.2.1]heptane-2,3-dicarboximide (9), and N
      farnesyl-7-oxabicyclo[2.2.1]heptane-2,3-dicarboximide (18), have shown the
      highest cytotoxicity, anti-proliferative and apoptotic effect against human liver
      carcinoma HepG2 cell lines, yet displayed no significant cytotoxic effect on
      normal murine embryonic liver BNL CL.2 cells. Their overall performance led us to
      believe that these two compounds might be potential candidates for anticancer
      drugs development. 

PMID- 24865601
TI  - Speciation and demographic history of Atlantic eels (Anguilla anguilla and A.
      rostrata) revealed by mitogenome sequencing.
AB  - Processes leading to speciation in oceanic environments without obvious physical
      barriers remain poorly known. European and American eel (Anguilla anguilla and A.
      rostrata) spawn in partial sympatry in the Sargasso Sea. Larvae are advected by
      the Gulf Stream and other currents towards the European/North African and North
      American coasts, respectively. We analyzed 104 mitogenomes from the two species
      along with mitogenomes of other Anguilla and outgroup species. We estimated
      divergence time between the two species to identify major events involved in
      speciation. We also considered two previously stated hypotheses: one where the
      ancestral species was present in only one continent but was advected across the
      Atlantic by ocean current changes and another where population declines during
      Pleistocene glaciations led to increasing vicariance, facilitating speciation.
      Divergence time was estimated to ~3.38 Mya, coinciding with the closure of the
      Panama Gateway that led to reinforcement of the Gulf Stream. This could have
      advected larvae towards European/North African coasts, in which case American eel
      would be expected to be the ancestral species. This scenario could, however, not
      be unequivocally confirmed by analyses of dN/dS, nucleotide diversity and
      effective population size estimates. Extended bayesian skyline plots showed
      fluctuations of effective population sizes and declines during glaciations, and
      thus also lending support to the importance of vicariance during speciation.
      There was evidence for positive selection at the ATP6 and possibly ND5 genes,
      indicating a role in speciation. The findings suggest an important role of ocean
      current changes in speciation of marine organisms. 

PMID- 24865604
TI  - Nimbolide B and nimbic acid B, phytotoxic substances in neem leaves with
      allelopathic activity.
AB  - Neem (Azadirachta indica) has been widely used as a traditional medicine and
      several bioactive compounds have been isolated from this species, but to date no
      potent allelopathic active substance has been reported. Therefore, we
      investigated possible allelopathic property and phytotoxic substances with
      allelopathic activity in neem. An aqueous methanol extract of neem leaves
      inhibited the growth of roots and shoots of cress, lettuce, alfalfa, timothy,
      crabgrass, ryegrass, barnyard grass and jungle rice. The extracts were then
      purified by several chromatographic runs while monitoring the inhibitory activity
      and two phytotoxic substances were isolated. The chemical structures of the two
      substances were determined by spectral data to correspond to novel compounds,
      nimbolide B (1) and nimbic acid B (2). Nimbolide B inhibited the growth of cress
      and barnyard grass at concentrations greater than 0.1-3.0 MUM. Nimbic acid B
      inhibited the growth of cress and barnyard grass at concentrations greater than
      0.3-1.0 MUM. These results suggest that nimbolide B and nimbic acid B may
      contribute to the allelopathic effects caused by neem leaves. 

PMID- 24865606
TI  - M(salen)-derived nitrogen-doped M/C (M = Fe, Co, Ni) porous nanocomposites for
      electrocatalytic oxygen reduction.
AB  - Carbonaceous materials containing non-precious metal and/or doped nitrogen have
      attracted tremendous attention in the field of electrochemical energy storage and
      conversion. Herein, we report the synthesis and electrochemical properties of a
      new family of nitrogen-doped metal/carbon (M/N/C, M = Fe, Co, Ni) nanocomposites.
      The M/N/C nanocomposites, in which metal nanoparticles are embedded in the highly
      porous nitrogen-doped carbon matrix, have been synthesized by simply pyrolyzing
      M(salen) (salen = N,N'-bis(salicylidene)-ethylenediamine) complex precursors. The
      prepared Co/N/C and Fe/N/C exhibit remarkable electrocatalytic activity (with
      onset potential of 0.96 V for Fe/N/C and half-wave potential of 0.80 V for
      Co/N/C) and high stability for the oxygen reduction reaction (ORR). The superior
      performance of the nanocomposites is attributed to their bimodal-pore structure,
      high surface area, as well as uniform distribution of high-density nitrogen and
      metal active sites.

PMID- 24865607
TI  - Neuropsychology and brain morphology in Klinefelter syndrome - the impact of
      genetics.
AB  - Klinefelter syndrome (KS, 47,XXY) is associated with increased psychiatric
      morbidity and cognitive disabilities, although the neuropsychological phenotype
      shows great variability. Androgen receptor polymorphism (CAG repeat length),
      skewed X-chromosome inactivation and parent-of-origin of the extra X-chromosome
      have been suggested to influence cognitive function and psychological traits.
      These issues have not been clarified for KS patients. We studied X-chromosome
      inactivation pattern, CAG repeat length and parent-of-origin in relation to
      educational and cohabitation status, personality and autism traits, psychological
      distress, cognitive function and brain volumes in 73 KS patients and 73 controls.
      Grey matter (GM) volume of left insula was significantly decreased in KS patients
      with skewed X-inactivation (z = 5.78) and we observed a borderline significant
      difference in global brain matter volume where KS patients with skewed X
      chromosome inactivation tended to have smaller brains. Skewed X-inactivation, CAG
      repeat length and parent-of-origin were not correlated with educational and
      marital status, personality traits, autism traits, and psychological distress,
      prevalence of depression and anxiety or cognitive function. Interestingly our
      results regarding brain volumes indicate that X-inactivation has an influence on
      GM volume in left insula and might also be related to global GM volume,
      indicating a possible effect of X-linked genes on the development of GM volume in
      KS patient. Skewed X-inactivation, CAG repeat length and parent-of-origin have no
      impact on the neuropsychological phenotype in KS (http://www.clinicaltrials.gov
      (Clinical trial NCT00999310)).

PMID- 24865608
TI  - One-day measurement to assess the auditory risks encountered by noise-exposed
      workers.
AB  - Noise is one of the most pervasive hazards in the workplace. Despite regulations
      and preventive measures, noise-induced hearing loss is common. The current
      reference test is pure-tone air-conduction audiometry (PTA), but this test cannot
      be used to detect early hearing loss. OBJECTIVE: In this study, we assess one-day
      auditory fatigue using both PTA and efferent reflexes (ER) measured using DPOAEs
      associated with contralateral acoustic stimulation (CAS DPOAEs). DESIGN: The
      noise exposure history, PTA, and ER detection were performed in seven different
      companies where the L(EX,8h) was 85 dB(A). Hearing was tested before and at the
      end of the working day. STUDY SAMPLE: Forty-six volunteers were selected to carry
      out this study. RESULTS: After a single working day, a greater impact of noise
      was measured using ER thresholds than PTA or DPOAEs. ER measurements are
      objective, easy to perform, and do not require a sound-attenuated booth.
      CONCLUSION: Screening workers by periodically measuring ER thresholds using CAS
      DPOAEs helps detect early changes in hearing status, before the onset of noise
      induced hearing loss. These tests can be readily applied as part of a hearing
      conservation program.

PMID- 24865609
TI  - Biochemical defects in minor spliceosome function in the developmental disorder
      MOPD I.
AB  - Biallelic mutations of the human RNU4ATAC gene, which codes for the minor
      spliceosomal U4atac snRNA, cause the developmental disorder, MOPD I/TALS. To
      date, nine separate mutations in RNU4ATAC have been identified in MOPD I
      patients. Evidence suggests that all of these mutations lead to abrogation of
      U4atac snRNA function and impaired minor intron splicing. However, the molecular
      basis of these effects is unknown. Here, we use a variety of in vitro and in vivo
      assays to address this question. We find that only one mutation, 124G>A, leads to
      significantly reduced expression of U4atac snRNA, whereas four mutations, 30G>A,
      50G>A, 50G>C and 51G>A, show impaired binding of essential protein components of
      the U4atac/U6atac di-snRNP in vitro and in vivo. Analysis of MOPD I patient
      fibroblasts and iPS cells homozygous for the most common mutation, 51G>A, shows
      reduced levels of the U4atac/U6atac.U5 tri-snRNP complex as determined by
      glycerol gradient sedimentation and immunoprecipitation. In this report, we
      establish a mechanistic basis for MOPD I disease and show that the inefficient
      splicing of genes containing U12-dependent introns in patient cells is due to
      defects in minor tri-snRNP formation, and the MOPD I-associated RNU4ATAC
      mutations can affect multiple facets of minor snRNA function. 

PMID- 24865611
TI  - Evolutionary patterns of Escherichia coli small RNAs and their regulatory
      interactions.
AB  - Most bacterial small RNAs (sRNAs) are post-transcriptional regulators of gene
      expression, exerting their regulatory function by base-pairing with their target
      mRNAs. While it has become evident that sRNAs play central regulatory roles in
      the cell, little is known about their evolution and the evolution of their
      regulatory interactions. Here we used the prokaryotic phylogenetic tree to
      reconstruct the evolutionary history of Escherichia coli sRNAs and their binding
      sites on target mRNAs. We discovered that sRNAs currently present in E. coli
      mainly accumulated inside the Enterobacteriales order, succeeding the appearance
      of other types of noncoding RNAs and concurrently with the evolution of a variant
      of the Hfq protein exhibiting a longer C-terminal region. Our analysis of the
      evolutionary ages of sRNA-mRNA interactions revealed that while all sRNAs were
      evolutionarily older than most of their known binding sites on mRNA targets, for
      quite a few sRNAs there was at least one binding site that coappeared with or
      preceded them. It is conceivable that the establishment of these first
      interactions forced selective pressure on the sRNAs, after which additional
      targets were acquired by fitting a binding site to the active region of the sRNA.
      This conjecture is supported by the appearance of many binding sites on target
      mRNAs only after the sRNA gain, despite the prior presence of the target gene in
      ancestral genomes. Our results suggest a selective mechanism that maintained the
      sRNAs across the phylogenetic tree, and shed light on the evolution of E. coli
      post-transcriptional regulatory network. 

PMID- 24865610
TI  - The folding of 5'-UTR human G-quadruplexes possessing a long central loop.
AB  - G-quadruplexes are widespread four-stranded structures that are adopted by G-rich
      regions of both DNA and RNA and are involved in essential biological processes
      such as mRNA translation. They are formed by the stacking of two or more G
      quartets that are linked together by three loops. Although the maximal loop
      length is usually fixed to 7 nt in most G-quadruplex-predicting software, it has
      already been demonstrated that artificial DNA G-quadruplexes containing two
      distal loops that are limited to 1 nt each and a central loop up to 30 nt long
      are likely to form in vitro. This report demonstrates that such structures
      possessing a long central loop are actually found in the 5'-UTRs of human mRNAs.
      Firstly, 1453 potential G-quadruplex-forming sequences (PG4s) were identified
      through a bioinformatic survey that searched for sequences respecting the
      requirement for two 1-nt long distal loops and a long central loop of 2-90 nt in
      length. Secondly, in vitro in-line probing experiments confirmed and
      characterized the folding of eight candidates possessing central loops of 10-70
      nt long. Finally, the biological effect of several G-quadruplexes with a long
      central loop on mRNA expression was studied in cellulo using a luciferase gene
      reporter assay. Clearly, the actual definition of G-quadruplex-forming sequences
      is too conservative and must be expanded to include the long central loop. This
      greatly expands the number of expected PG4s in the transcriptome. Consideration
      of these new candidates might aid in elucidating the potentially important
      biological implications of the G-quadruplex structure. 

PMID- 24865612
TI  - Native mitochondrial RNA-binding complexes in kinetoplastid RNA editing differ in
      guide RNA composition.
AB  - Mitochondrial mRNAs in kinetoplastids require extensive U-insertion/deletion
      editing that progresses 3'-to-5' in small blocks, each directed by a guide RNA
      (gRNA), and exhibits substrate and developmental stage-specificity by unsolved
      mechanisms. Here, we address compositionally related factors, collectively known
      as the mitochondrial RNA-binding complex 1 (MRB1) or gRNA-binding complex (GRBC),
      that contain gRNA, have a dynamic protein composition, and transiently associate
      with several mitochondrial factors including RNA editing core complexes (RECC)
      and ribosomes. MRB1 controls editing by still unknown mechanisms. We performed
      the first next-generation sequencing study of native subcomplexes of MRB1,
      immunoselected via either RNA helicase 2 (REH2), that binds RNA and associates
      with unwinding activity, or MRB3010, that affects an early editing step. The
      particles contain either REH2 or MRB3010 but share the core GAP1 and other
      proteins detected by RNA photo-crosslinking. Analyses of the first editing blocks
      indicate an enrichment of several initiating gRNAs in the MRB3010-purified
      complex. Our data also indicate fast evolution of mRNA 3' ends and strain
      specific alternative 3' editing within 3' UTR or C-terminal protein-coding
      sequence that could impact mitochondrial physiology. Moreover, we found robust
      specific copurification of edited and pre-edited mRNAs, suggesting that these
      particles may bind both mRNA and gRNA editing substrates. We propose that
      multiple subcomplexes of MRB1 with different RNA/protein composition serve as a
      scaffold for specific assembly of editing substrates and RECC, thereby forming
      the editing holoenzyme. The MRB3010-subcomplex may promote early editing through
      its preferential recruitment of initiating gRNAs. 

PMID- 24865614
TI  - Cellular transport of microcystin-LR in rainbow trout (Oncorhynchus mykiss)
      across the intestinal wall: possible involvement of multidrug resistance
      associated proteins.
AB  - We studied Abcc mediated-transport in middle and posterior intestine of the
      rainbow trout, Oncorhynchus mykiss. Luminal and serosal transport were evaluated
      in everted and non-everted intestinal sacs, respectively, incubated with 1-chloro
      2,4-dinitrobenzene (CDNB; 200 MUM). CDNB enters the cells and is conjugated with
      glutathione via glutathione S-transferase (GST) to form 2,4-dinitrophenyl-S
      glutathione (DNP-SG), a known Abcc substrate. DNP-SG concentration in the bath
      was recorded every 10 min, in order to calculate the mass-specific transport
      rate. For evaluating the possible involvement of Abcc proteins in microcystin-LR
      (MCLR) transport, 1.135 MUM MCLR was added to the bath or inside the sacs, in
      everted or non-everted preparations, respectively. Both luminal and serosal DNP
      SG efflux were significantly inhibited by MCLR. A concentration-response curve
      obtained using strips from middle intestine yielded an IC50 value of 1.33 MUM
      MCLR. The Abcc inhibitor, MK571 produced concentration-dependent inhibition of
      DNP-SG similar to that produced by MCLR. Since competition of MCLR and CDNB as
      GST substrates could bias the DNP-SG transport results, we evaluated the effects
      of MCLR on calcein efflux, which does not depend on GST activity. We applied the
      non-fluorescent, cell-permeant compound calcein-AM (0.25 MUM) to middle
      intestinal strips and recorded the efflux of its hydrolysis product, the
      fluorescent Abcc substrate calcein. 2.27 MUM MCLR and 3 MUM MK571 inhibited
      calcein efflux (17.39 and 20.2%, respectively). Finally, MCLR interaction with
      Abcc transporters was evaluated by measuring its toxic intracellular effects.
      Middle intestinal segments were incubated in saline solution with 1.135 MUM MCLR
      (MC1), 2.27 MUM MCLR (MC2), 3 MUM MK571 (MK) or 1.135 MUM MCLR+3 MUM MK571
      (MC1/MK). After 1h, GSH concentration, protein phosphatase 1 and 2A (PP1, PP2A)
      and GST activities were measured in each segment. MC1did not produce significant
      effect while MC1/MK and MC2 significantly inhibited PP1and PP2A in similar
      proportions (34-49%). MK alone significantly increased PP2A activity (40%) with
      no effect in any other variable. GST activity and GSH concentration were not
      affected by any treatment. Concentration-response curves for MCLR (1.135 to 13.62
      MUM) alone or plus 3 or 6 MUM MK571 were obtained using PP1 activity as response
      variable. The IC50 values were 1.0, 0.52, and 0.37 MUM, respectively. Our results
      suggest that O. mykiss enterocytes are capable of eliminating MCLR by GST
      mediated conjugation and luminal excretion through an Abcc-like apical
      transporter. This mechanism would prevent toxic effects and reduce the toxin
      uptake into the blood, which is likely mediated by basolateral Abccs.

PMID- 24865613
TI  - Mono-substituted isopropylated triaryl phosphate, a major component of Firemaster
      550, is an AHR agonist that exhibits AHR-independent cardiotoxicity in zebrafish.
AB  - Firemaster 550 (FM550) is an additive flame retardant mixture used within
      polyurethane foam and is increasingly found in house dust and the environment due
      to leaching. Despite the widespread use of FM550, very few studies have
      investigated the potential toxicity of its ingredients during early vertebrate
      development. In the current study, we sought to specifically investigate mono
      substituted isopropylated triaryl phosphate (mITP), a component comprising
      approximately 32% of FM550, which has been shown to cause cardiotoxicity during
      zebrafish embryogenesis. Previous research showed that developmental defects are
      rescued using an aryl hydrocarbon receptor (AHR) antagonist (CH223191),
      suggesting that mITP-induced toxicity was AHR-dependent. As zebrafish have three
      known AHR isoforms, we used a functional AHR2 knockout line along with AHR1A- and
      AHR1B-specific morpholinos to determine which AHR isoform, if any, mediates mITP
      induced cardiotoxicity. As in silico structural homology modeling predicted that
      mITP may bind favorably to both AHR2 and AHR1B isoforms, we evaluated AHR
      involvement in vivo by measuring CYP1A mRNA and protein expression following
      exposure to mITP in the presence or absence of CH223191 or AHR-specific
      morpholinos. Based on these studies, we found that mITP interacts with both AHR2
      and AHR1B isoforms to induce CYP1A expression. However, while CH223191 blocked
      mITP-induced CYP1A induction and cardiotoxicity, knockdown of all three AHR
      isoforms failed to block mITP-induced cardiotoxicity in the absence of detectable
      CYP1A induction. Overall, these results suggest that, while mITP is an AHR
      agonist, mITP causes AHR-independent cardiotoxicity through a pathway that is
      also antagonized by CH223191. 

PMID- 24865615
TI  - Hypoxia lowers SLC30A8/ZnT8 expression and free cytosolic Zn2+ in pancreatic beta
      cells.
AB  - AIMS/HYPOTHESIS: Hypoxic damage complicates islet isolation for transplantation
      and may contribute to beta cell failure in type 2 diabetes. Polymorphisms in the
      SLC30A8 gene, encoding the secretory granule zinc transporter 8 (ZnT8), influence
      type 2 diabetes risk, conceivably by modulating cytosolic Zn(2+) levels. We have
      therefore explored the role of ZnT8 and cytosolic Zn(2+) in the response to
      hypoxia of pancreatic islet cells. METHODS: Human, mouse or rat islets were
      isolated and exposed to varying O2 tensions. Cytosolic free zinc was measured
      using the adenovirally expressed recombinant targeted zinc probe eCALWY4. Gene
      expression was measured using quantitative (q)RT-PCR, western (immuno-) blotting
      or immunocytochemistry. Beta cells were identified by insulin immunoreactivity.
      RESULTS: Deprivation of O2 (1% vs 5% or 21%) for 24 h lowered free cytosolic
      Zn(2+) concentrations by ~40% (p < 0.05) and ~30% (p < 0.05) in mouse and human
      islet cells, respectively. Hypoxia similarly decreased SLC30A8 mRNA expression in
      islets, and immunoreactivity in beta cells. Implicating lowered ZnT8 levels in
      the hypoxia-induced fall in cytosolic Zn(2+), genetic ablation of Slc30a8 from
      mouse islets lowered cytosolic Zn(2+) by ~40% (p < 0.05) and decreased the
      induction of metallothionein (Mt1, Mt2) genes. Cell survival in the face of
      hypoxia was enhanced in small islets of older (>12 weeks) Slc30a8 null mice vs
      controls, but not younger animals. CONCLUSIONS/INTERPRETATION: The response of
      pancreatic beta cells to hypoxia is characterised by decreased SLC30A8 expression
      and lowered cytosolic Zn(2+) concentrations. The dependence on ZnT8 of hypoxia
      induced changes in cell survival may contribute to the actions of SLC30A8
      variants on diabetes risk in humans.

PMID- 24865617
TI  - Cause-specific neonatal deaths in rural Bangladesh, 1987-2005: levels, trends,
      and determinants.
AB  - This paper reports on an analysis of neonatal mortality from communicable and non
      communicable diseases in Bangladesh. The competing-risks model employed
      incorporated both observed and unobserved heterogeneity and allowed the two
      heterogeneity terms to be correlated. The data used came from the Health and
      Demographic Surveillance System, Matlab. The results confirm the conclusions of
      previous studies about the levels, trends, and causes of neonatal death in the
      Matlab area: the education of the mother helps protect her children from death
      from both communicable and non-communicable diseases; the children of a father in
      a low-status occupation are particularly vulnerable to death from communicable
      diseases; and children born to mothers aged less than 20 face a particularly high
      risk of dying from a non-communicable disease. The risks of dying from a
      communicable disease and from a non-communicable disease were both found to fall
      significantly as the distance to the nearest health centre decreased. 

PMID- 24865616
TI  - Molecular and pathological studies in the posterior interosseous nerve of
      diabetic and non-diabetic patients with carpal tunnel syndrome.
AB  - AIMS/HYPOTHESIS: We sought to establish the molecular and pathological changes
      predisposing diabetic and non-diabetic patients to the development of carpal
      tunnel syndrome (CTS). METHODS: The posterior interosseous nerve (PIN) was
      biopsied in 25 diabetic and 19 non-diabetic patients undergoing carpal tunnel
      decompression for CTS. Detailed morphometric and immunohistological analyses were
      performed in the nerve biopsy. RESULTS: In diabetic patients median nerve distal
      motor latency was prolonged (p < 0.05 vs non-diabetic patients), PIN myelinated
      fibre density (p < 0.05), fibre area (p < 0.0001) and axon area (p < 0.0001) were
      reduced, the percentage of unassociated Schwann cell profiles (p < 0.0001) and
      unmyelinated axon density (p < 0.0001) were increased and the axon diameter was
      reduced (p < 0.0001). Endoneurial capillary basement membrane area was increased
      (p < 0.0001) in diabetic patients, but endothelial cell number was increased (p <
      0.01) and luminal area was reduced (p < 0.05) in non-diabetic patients with CTS.
      There was no difference in the expression of hypoxia-inducible factor 1alpha
      between diabetic and non-diabetic patients with CTS. However, the expression of
      vascular endothelial growth factor A (VEGF) (p < 0.05) and its receptors VEGFR-1
      (p < 0.01) and VEGFR-2 (p < 0.05) was significantly increased in diabetic
      patients, particularly those with type 1 diabetes, and related to the severity of
      nerve fibre pathology. CONCLUSIONS/INTERPRETATION: This study demonstrates
      increased nerve fibre and microvascular pathology in relation to enhanced
      expression of VEGF and its receptors in a non-compressed nerve in diabetic
      compared with non-diabetic patients with CTS. It therefore provides a potential
      molecular and pathological basis for the predisposition of diabetic patients to
      the development of CTS.

PMID- 24865618
TI  - Assessment of long-term donor-site morbidity after harvesting the latissimus
      dorsi flap for neonatal myelomeningocele repair.
AB  - BACKGROUND AND AIM: The latissimus dorsi flap (LDF) has been employed very
      successfully over decades to cover large soft-tissue defects. Its donor-site
      morbidity has been extensively investigated in adults - but not in children - and
      is considered to be nonrestrictive. The aim of this long-term study was to assess
      donor-site morbidity with the modified Constant score more than 8 years after
      coverage of large myelomeningocele (MMC) defects with a reverse latissimus dorsi
      flap. METHODS: Within the first days after birth, the reverse latissimus dorsi
      muscle flap was used uni- or bilaterally in three neonates to cover a large MMC
      defect. Bilateral shoulder function was tested more than 8 years postoperatively
      according to the modified Constant score. RESULTS: The mean age at follow-up was
      11.7 years. None of the patients experienced any pain or shoulder restrictions
      during normal daily activities. They all managed to position both of their arms
      comfortably above the head. Forward flexion was normal in all patients as was
      abduction and external rotation. Dorsal extension was minimally reduced on the
      operated side. Internal rotation was symmetric in all patients; the extent of
      active movement varied from excellent to poor. CONCLUSIONS: Our long-term data
      suggest that there is no specific and significant impairment of shoulder function
      after using the distally pedicled reverse LDF for neonatal MMC repair.

PMID- 24865621
TI  - Intraoral pressures produced by thirteen semi-occluded vocal tract gestures.
AB  - The use of semi-occluded vocal tract (SOVT) exercises as habilitative and
      rehabilitative tools has grown substantially in the past two decades. As the use
      of these exercises has grown, so too has the number of variations of the
      phonatory gestures used to create oral semi-occlusions. While much of the
      research on SOVT exercises to this point has been conducted using straw
      phonation, there has been little discussion or investigation regarding how other
      phonatory gestures that are considered to be SOVT compare to one another. The
      current study sought to measure the intraoral pressure produced by 13 phonatory
      gestures generally thought of as oral semi-occlusions. Twenty subjects (10 male,
      10 female) produced three tokens of each gesture, and intraoral pressure was
      recorded via a thin, flexible-cannula pressure transducer. Pressures ranged
      between 0.1 and 1.0 kPa, but varied significantly between gestures and between
      subjects. 

PMID- 24865620
TI  - Resonance tube phonation in water: High-speed imaging, electroglottographic and
      oral pressure observations of vocal fold vibrations--a pilot study.
AB  - Phonation into glass tubes ('resonance tubes'), keeping the free end of the tube
      in water, has been a frequently used voice therapy method in Finland and more
      recently also in other countries. The purpose of this exploratory study was to
      investigate what effects tube phonation with and without water has on the larynx.
      Two participants were included in the study. The methods used were high-speed
      imaging, electroglottographic observations of vocal fold vibrations, and
      measurements of oral pressure during tube phonation. Results showed that the
      fluctuation in the back pressure during tube phonation in water altered the vocal
      fold vibrations. In the high-speed imaging, effects were found in the open
      quotient and amplitude variation of the glottal opening. The open quotient
      increased with increasing water depth (from 2 cm to 6 cm). A modulation effect by
      the water bubbles on the vocal fold vibrations was seen both in the high-speed
      glottal area tracings and in the electroglottography signal. A second experiment
      revealed that the increased average oral pressure was largely determined by the
      water depth. The increased open quotient can possibly be explained by an
      increased abduction of the vocal folds and/or a reduced transglottal pressure.
      The back pressure of the bubbles also modulates glottal vibrations with a
      possible 'massage' effect on the vocal folds. This effect and the well-defined
      average pressure increase due to the known water depth are different from those
      of other methods using a semi-occluded vocal tract. 

PMID- 24865622
TI  - Effect of hemodiafiltration with endogenous reinfusion on overt idiopathic
      chronic inflammation in maintenance hemodialysis patients: a multicenter
      longitudinal study.
AB  - Chronic inflammation is widely diffuse in maintenance hemodialysis (MHD) patients
      and is associated with poor survival. Hemodiafiltration with endogenous
      reinfusion (HFR) is a dialysis technique, highly biocompatible, able to adsorb
      proinflammatory cytokines and to decrease amino acids and antioxidants loss.
      These features could be helpful in MHD patients affected by idiopathic chronic
      inflammation, but this issue remains to be elucidated. We performed a multicenter
      longitudinal study to assess the effect of the switching from bicarbonate HD to
      HFR in patients with serum C-reactive Protein (CRP) > 5 mg/L coupled with albumin
      <4.0 g/dL in the last 6 months. We enrolled 24/176 (14%) patients, of which 20
      patients were assessed at 4 months and 18 completed the study. We excluded 11
      patients with evident causes of inflammation. At baseline, serum levels of CRP
      (18.7[7.0-39.4] mg/L) and albumin (3.5[3.3-3.7] g/dL) were significantly
      correlated (r = -0.49; P = 0.028). The effect on CRP and albumin was almost
      evident in the first 4 months and remained stable until to eighth month. A strict
      correlation (R = -0.49; 0.040) between percentage change of CRP (-35%) and
      albumin (+14%) after 8 months of HFR. These effects were associated with the
      reduction of IL-6, IL-1beta, and TNF-alpha and the increment of pre-albumin and
      leptin, whereas the serum levels of Branched Chain Amino Acid (BCAA) remained
      unchanged. In MHD patients affected by idiopathic chronic inflammation the
      switching from BHD to HFR is associated with improvement of inflammation. Whether
      these favorable effects may modify the outcomes of these high-risk patients needs
      to be confirmed by studies ad hoc. 

PMID- 24865619
TI  - Substance abuse treatment patients with early onset cocaine use respond as well
      to contingency management interventions as those with later onset cocaine use.
AB  - Early onset drug use is associated with increased risk of developing substance
      use disorders, but relatively little is known about the correlates of early drug
      use among adults receiving treatment. A retrospective analysis of a randomized
      study of contingency management treatment compared cocaine-dependent patients who
      reported initial cocaine use at age 14 or younger (n = 41) to those who began
      using after age 14 (n = 387). Patients with early onset cocaine use had more
      legal and psychiatric problems than those who initiated cocaine use later.
      Patients with early-onset cocaine use also dropped out of treatment sooner and
      achieved less sustained abstinence than those who began using at older ages, but
      the interaction between age of first use and treatment condition was not
      significant. Early-onset cocaine use is associated with persistent psychosocial
      problems and an overall poor response to treatment. However, contingency
      management is efficacious in improving outcomes in early onset cocaine users.

PMID- 24865624
TI  - PDE inhibitors currently in early clinical trials for the treatment of asthma.
AB  - INTRODUCTION: PDE inhibitors could be useful in the treatment of asthma because
      of their bronchodilator and/or anti-inflammatory activities. Recently, some
      selective PDE3, PDE4 and PDE3/4 inhibitors have been shown to have beneficial
      effects in patients with asthma suggesting that such drugs may offer novel
      therapeutic options for the treatment of this disease. AREAS COVERED: The authors
      describe the main PDE families that could be involved in asthma as well as the
      PDE inhibitors that have been evaluated for the treatment of asthma. EXPERT
      OPINION: Although the potential therapeutic utility of PDE inhibitors has been
      demonstrated in various animal models of asthma, their clinical efficacy have
      been restricted by the dose-limiting side effects; no PDE inhibitor has yet been
      approved for the treatment of patients with asthma. Although new PDE inhibitors
      have been synthesised, most data are from cellular and tissue-level studies with
      human trials still on the horizon. Apparently, only CHF 6001, an inhaled PDE4
      inhibitor, and RPL554, a dual PDE3/4 inhibitor, are still under clinical
      development. Further data from these new drugs are eagerly anticipated to better
      understand where these drugs might stand in the future treatment of asthma.

PMID- 24865625
TI  - More or less is fine: an undercover work of DKK1 in anthrax toxin uptake.

PMID- 24865626
TI  - American Association of Clinical Endocrinologists 23rd Annual Scientific and
      Clinical Congress (AACE 2014).

PMID- 24865629
TI  - Connexin 43 expression in Sprague-Dawley rat seminiferous epithelium after in
      utero exposure to flutamide.
AB  - This study explored the expression of connexin 43 (Cx43) in the testes of
      prepubertal Sprague-Dawley (SD) rats following in utero flutamide (Flu) exposure.
      Connexins constitute the major protein type in gap junctions. Connexin 43, the
      most prominent connexin family member expressed by testes, is localized at the
      base of seminiferous tubules in humans and rodents, and may be involved in
      fertility. Flutamide was injected subcutaneously into pregnant SD rats on
      gestational days 12-21 (25 mg/kg/day). Immunohistochemistry, Western blotting,
      and real-time PCR was used to investigate the distribution and the expression of
      Cx43 protein and mRNA in the testis on postnatal day 20 (PD20). Following Flu
      exposure, Cx43 was observed between Sertoli cells in the seminiferous tubules. On
      PD20, no Cx43 protein was expressed by the spermatogonial cell layer of the
      seminiferous tubules in the controls, but was observed in the Flu-exposed group.
      Western blotting showed that Cx43 was expressed at significantly lower levels in
      Flu-exposed testes than controls on PD20 (p < 0.001). On PD20, levels of Cx43
      mRNA in undescended Flu-exposed testes were significantly lower than in controls
      (p < 0.05) and descended Flu-exposed testes (p < 0.01). After Flu-exposure in the
      rat embryonic period, Cx43 mRNA and protein expression were downregulated, and
      its distribution in the seminiferous tubules was abnormal.

PMID- 24865627
TI  - Activation of MKK9-MPK3/MPK6 enhances phosphate acquisition in Arabidopsis
      thaliana.
AB  - Despite the abundance of phosphorus in soil, very little is available as
      phosphate (Pi) for plants. Plants often experience low Pi (LP) stress. Intensive
      studies have been conducted to reveal the mechanism used by plants to deal with
      LP; however, Pi sensing and signal transduction pathways are not fully
      understood. Using in-gel kinase assays, we determined the activities of MPK3 and
      MPK6 in Arabidopsis thaliana seedlings under both LP and Pi-sufficient (Murashige
      and Skoog, MS) conditions. Using MKK9 mutant transgenic and crossed mutants, we
      analyzed the functions of MPK3 and MPK6 in regulating Pi responses of seedlings.
      The regulation of Pi responses by downstream components of MKK9-MPK3/MPK6 was
      also screened. LP treatment activated MPK3 and MPK6. Under both LP and MS
      conditions, mpk3 and mpk6 seedlings took up and accumulated less Pi than the wild
      type; activation of MKK9-MPK3/MPK6 in transgenic seedlings induced the
      transcription of Pi acquisition-related genes and enhanced Pi uptake and
      accumulation, whereas its activation suppressed the transcription of anthocyanin
      biosynthetic genes and anthocyanin accumulation; WRKY75 was downstream of MKK9
      MPK3/MPK6 when regulating the accumulation of Pi and anthocyanin, and the
      transcription of Pi acquisition-related and anthocyanin biosynthetic genes. These
      results suggest that the MKK9-MPK3/MPK6 cascade is part of the Pi signaling
      pathway in plants. 

PMID- 24865630
TI  - AAGL practice report: Morcellation during uterine tissue extraction.

PMID- 24865628
TI  - Role of 3.0 T multiparametric MRI in local staging in prostate cancer and
      clinical implications for radiation oncology.
AB  - PURPOSE: To evaluate the accuracy of preoperative 3T multiparametric magnetic
      resonance imaging (3TmMRI) for local staging of prostate cancer and its influence
      on the decision to change the clinical target volume (CTV), total dose and
      hormonal therapy when treating prostate cancer patients with radiotherapy.
      METHODS: From 2009 to 2013, 150 patients, who had confirmed prostate cancer and
      underwent a 3TmMRI before treatment with radical prostatectomy or radical
      radiation therapy, were included. Radiation therapy treatment (CTV, total dose
      and hormonal therapy) was initially determined on the basis of the clinical
      information, and radiation therapy plan was reevaluated after 3TmMRI review. The
      value of preoperative 3TmMRI in local staging and in the decision of radiotherapy
      treatment according to NCCN risk classification was analyzed. RESULTS: 3TmMRI
      performed correct, over- and under staging in 78.7 % (37/47), 6.3 % (3/47), 14.8
      % patients (7/47), respectively. 3TmMRI identified 6 cT2a, 7 cT2b, 28 cT2c, 3
      cT3a, 3 cT3b tumors. At final pathology, 5 tumors were classified as pT2a, 5 as
      pT2b, 30 as pT2c, 4 as pT3a, 3 as pT3b. After reviewing the MRI reports, the
      initial radiotherapy and hormonal therapy plan was changed in 33.9 % patients
      (35/103). CONCLUSIONS: In our group of patients, 3TmMRI has been a reliable
      technique providing an optimal staging for prostate cancer. Its routine use could
      induce important changes in radiation therapy treatments in a significant number
      of such patients. However, more additional studies are needed to clarify this
      issue.

PMID- 24865631
TI  - Comparison of robotic-assisted and conventional laparoscopy in the management of
      adnexal masses.
AB  - STUDY OBJECTIVE: To compare the outcome of robotic-assisted laparoscopy vs
      conventional laparoscopy in the management of ovarian masses. DESIGN:
      Retrospective cohort (Canadian Task Force classification II-3). SETTING: Academic
      medical centre in the northeast United States. PATIENTS: Retrospective medical
      record review of 71 consecutive patients with presumed benign ovarian masses.
      INTERVENTION: Robotic-assisted laparoscopy in 30 patients with presumed benign
      ovarian masses was compared with conventional laparoscopy in 41 patients.
      MEASUREMENTS AND MAIN RESULTS: Operative outcomes including operative time,
      estimated blood loss, length of hospital stay, and complications were recorded.
      Standard statistical analysis was used to compare the outcomes in the 2 groups.
      Mean (SD) operative time in the robotic group was 1.95 (0.63) hours, which was
      significantly longer than in the conventional laparoscopic group, 1.28 (0.83)
      hours (p = .04). Estimated blood loss in the robotic group was 74.52 (56.23) mL,
      which was not significantly different from that in the conventional laparoscopic
      group, 55.97 (49.18) mL. There were no significant differences in length of
      hospital stay between the robotic and conventional laparoscopic groups: 1.20
      (0.78) days and 1.48 (0.63). Conversion to laparotomy was not necessary in either
      group of patients. Intraoperative and postoperative complications were similar
      between the 2 groups. CONCLUSION: Robotic-assisted laparoscopy is a safe and
      efficient technique for management of various types of ovarian masses. However,
      conventional laparoscopy is preferred for management of ovarian masses because of
      shorter operative time. Prospective studies are needed to evaluate the outcomes
      of robotic-assisted laparoscopic management of benign and malignant ovarian
      neoplasms.

PMID- 24865632
TI  - Use of a hysteroscopic morcellator to resect miscarriage in a woman with
      recurrent Asherman's syndrome.
AB  - Uterine curettage may result in formation of intrauterine adhesions, which can
      predispose to recurrent miscarriage [1]. Herein is presented a video case report
      of a 24-year-old woman with recurrent miscarriages and recurrent intrauterine
      adhesions after treatment of non-progressive pregnancies. Targeted intrauterine
      pregnancy tissue removal using a hysteroscopic morcellator was performed to
      reduce the risk of adhesion recurrence. Successful removal of products of
      conception, without subsequent adhesion formation, and an ongoing viable
      pregnancy followed. Selective targeted removal of products of conception may
      offer some advantage to women with a predisposition to recurrent Asherman's
      syndrome.

PMID- 24865633
TI  - Decavanadate in vitro and in vivo effects: facts and opinions.
AB  - This review covers recent advances in the understanding of the in vitro and in
      vivo effects of decavanadate, (V10O28)(6-), particularly in mitochondria. In vivo
      toxicological studies involving vanadium rarely account for the fact that under
      physiological conditions some vanadium may be present in the form of the
      decavanadate ion, which may behave differently from ortho- and metavanadates. It
      has for example been demonstrated that vanadium levels in heart or liver
      mitochondria are increased upon decavanadate exposure. Additionally, in vitro
      studies have shown that mitochondrial depolarization (IC50, 40 nM) and oxygen
      consumption (IC50, 99 nM) are strongly affected by decavanadate, which causes
      reduction of cytochrome b (complex III). We review these recent findings which
      together suggest that the observed cellular targets, metabolic pathway and
      toxicological effects differ according to the species of vanadium present.
      Finally, the toxicological effects of decavanadate depend on several factors such
      as the mode of administration, exposure time and type of tissue. 

PMID- 24865634
TI  - Rolf Bernander (1956-2014): pioneer of the archaeal cell cycle.
AB  - On 19 January 2014 Rolf ('Roffe') Bernander passed away unexpectedly. Rolf was a
      dedicated scientist; his research aimed at unravelling the cell biology of the
      archaeal domain of life, especially cell cycle-related questions, but he also
      made important contributions in other areas of microbiology. Rolf had a professor
      position in the Molecular Evolution programme at Uppsala University, Sweden for
      about 8 years, and in January 2013 he became chair professor at the Department of
      Molecular Biosciences, The Wenner-Gren Institute at Stockholm University in
      Sweden. Rolf was an exceptional colleague and will be deeply missed by his family
      and friends, and the colleagues and co-workers that he leaves behind in the
      scientific community. He will be remembered for his endless enthusiasm for
      science, his analytical mind, and his quirky sense of humour.

PMID- 24865635
TI  - Prognostic factors in continuous hemofiltration therapy for patients with
      cardiorenal syndrome.
AB  - AIMS: The aims of this study were to investigate the efficacy and identify the
      prognostic factors of continuous hemofiltration in patients with cardiorenal
      syndrome (CRS) and, finally, to optimally select patients who could benefit more
      from this therapy. METHODS: A total of 59 patients with CRS type 1 or type 2
      treated with continuous hemofiltration were enrolled. We collected their clinical
      data and divided them into 2 groups according to their survival or death during
      hospitalization to conduct a retrospective analysis on factors affecting
      mortality. RESULTS: The following items were significantly different between the
      survival (n = 30) and death (n = 29) groups: serum creatinine, serum total
      bilirubin, direct bilirubin, white blood cells, hemoglobin, hematocrit, left
      ventricular end-diastolic diameter, left ventricular end-systolic diameter,
      systolic blood pressure and mean arterial pressure before hemofiltration, and
      average dehydration volume during the hemofiltration process. Leukocytosis was a
      risk factor for death (OR 1.242, 95% CI 1.242-1.480), and elevated sCr was not a
      key negative factor in the prognosis of CRS (OR 0.994, 95% CI 0.989-1.000).
      CONCLUSIONS: Cardiac function before hemofiltration and the amount of dehydration
      during the hemofiltration process both affected the prognosis. Infection and
      fluid overload condition at the beginning of hemofiltration were independently
      associated with mortality during hospitalization.

PMID- 24865637
TI  - Arm swing in human walking: what is their drive?
AB  - Although previous research has studied arm swing during walking, to date, it
      remains unclear what the contribution of passive dynamics versus active muscle
      control to arm swing is. In this study, we measured arm swing kinematics with 3D
      motion analysis. We used a musculoskeletal model in OpenSim and generated dynamic
      simulations of walking with and without upper limb muscle excitations. We then
      compared arm swing amplitude and relative phase during both simulations to verify
      the extent to which passive dynamics contribute to arm swing. The results confirm
      that passive dynamics are partly responsible for arm swing during walking.
      However, without muscle activity, passive swing amplitude and relative phase
      decrease significantly (both p<0.05), the latter inducing a more in-phase swing
      pattern of the arms. Therefore, we conclude that muscle activity is needed to
      increase arm swing amplitude and modify relative phase during human walking to
      obtain an out-phase movement relative to the legs. 

PMID- 24865638
TI  - Memory deficits correlate with tau and spine pathology in P301S MAPT transgenic
      mice.
AB  - AIM: P301S MAPT transgenic mice (P301S mice) are a widely used model of
      frontotemporal dementia and parkinsonism linked to chromosome 17 with tau
      pathology (FTDP-17-tau). However, a systematic correlation between cognitive
      deficits and cellular tau pathology at different ages is still missing.
      Therefore, our study investigated memory deficits of P301S mice in relation to
      pathological tau species and dendritic spine pathology throughout adulthood.
      METHODS: We analysed P301S mice behaviourally with the novel open field, rotarod,
      and Morris water maze tests to measure deficits in locomotion, balance and
      cognition, respectively; immunohistochemically with different tau antibodies for
      specific tau species; and with Golgi staining for dendritic spine pathology.
      RESULTS: We confirmed the occurrence of locomotor deficits at an age of 5 months
      and newly report memory deficits from 2.5 months of age onwards. At this early
      age, MC1 and CP13, but not AT180 immunoreactivity, was prominent in the
      hippocampus of P301S mice. Neuronal cell loss in the hippocampus of P301S mice
      was not observed to occur till 6 months of age. However, there was a significant
      reduction in the density of dendritic spines from young adulthood onwards in
      hippocampal pyramidal neurones. CONCLUSION: In P301S mice, memory deficits
      precede the onset of locomotor dysfunction and coincide with the appearance of
      conformationally changed, S202-phosphorylated tau and reduced spine density in
      the absence of neuronal cell loss in the hippocampus. Our finding provides
      insights into the toxic effects of different tau species in vivo and may
      facilitate the development of new therapies against neurodegenerative
      tauopathies.

PMID- 24865639
TI  - Suspected coronary ostium calcification identified as a protruding stent by
      epiaortic echography.
AB  - A 76-year-old male patient was admitted for mitral valvuloplasty. He had suffered
      a myocardial infarction 7 months earlier, and two stents had been inserted in the
      left main coronary artery and left circumflex artery. Intraoperative
      transesophageal echocardiography revealed a 10 * 8 mm echogenic mass at the
      ostium of the left main coronary artery. We initially suspected severe
      atheromatous calcification at the coronary ostium, which might require aortotomy
      and removal, but we decided to perform an epiaortic ultrasonographic scan first
      to obtain better images and reevaluate. Epiaortic scanning with a linear
      sonographic probe identified the mass as a protruding coronary stent.

PMID- 24865640
TI  - Metabolic spectroscopy of inflammation in a bleomycin-induced lung injury model
      using hyperpolarized 1-(13) C pyruvate.
AB  - Metabolic activity in the lung is known to change in response to external
      insults, inflammation, and cancer. We report measurements of metabolism in the
      isolated, perfused rat lung of healthy controls and in diseased lungs undergoing
      acute inflammation using hyperpolarized 1-(13) C-labeled pyruvate. The overall
      apparent activity of lactate dehydrogenase is shown to increase significantly (on
      average by a factor of 3.3) at the 7 day acute stage and to revert substantially
      to baseline at 21 days, while other markers indicating monocarboxylate uptake and
      transamination rate are unchanged. Elevated lung lactate signal levels correlate
      well with phosphodiester levels as determined with (31) P spectroscopy and with
      the presence of neutrophils as determined by histology, consistent with a
      relationship between intracellular lactate pool labeling and the density and type
      of inflammatory cells present. We discuss several alternate hypotheses, and
      conclude that the most probable source of the observed signal increase is direct
      uptake and metabolism of pyruvate by inflammatory cells and primarily
      neutrophils. This signal is seen in high contrast to the low baseline activity of
      the lung.

PMID- 24865641
TI  - Carbofuran induced oxidative stress mediated alterations in Na+-K+-ATPase
      activity in rat brain: amelioration by vitamin E.
AB  - Pesticides cause oxidative stress and adversely influence Na(+)-K(+)-ATPase
      activity in animals. Since impact of carbofuran has not been properly studied in
      the mammalian brain, the ability of carbofuran to induce oxidative stress and
      modulation in Na(+)-K(+)-ATPase activity and its amelioration by vitamin E was
      performed. The rats divided into six groups received two different doses of
      carbofuran (15% and 30% LD50) for 15 days. The results suggested that the
      carbofuran treatment caused a significant elevation in levels of malonaldehyde
      and reduced glutathione and sharp inhibition in the activities of super oxide
      dismutase, catalase, and glutathione-S-transferase; the effect being dose
      dependent. Carbofuran at different doses also caused sharp reduction in the
      activity of Na(+)-K(+)-ATPase. The pretreatment of vitamin E, however, showed a
      significant recovery in these indices. The pretreatment of rats with vitamin E
      offered protection from carbofuran-induced oxidative stress.

PMID- 24865643
TI  - Driving and dementia: a clinical decision pathway.
AB  - OBJECTIVE: This study aimed to develop a pathway to bring together current UK
      legislation, good clinical practice and appropriate management strategies that
      could be applied across a range of healthcare settings. METHODS: The pathway was
      constructed by a multidisciplinary clinical team based in a busy Memory
      Assessment Service. A process of successive iteration was used to develop the
      pathway, with input and refinement provided via survey and small group meetings
      with individuals from a wide range of regional clinical networks and diverse
      clinical backgrounds as well as discussion with mobility centres and Forum of
      Mobility Centres, UK. RESULTS: We present a succinct clinical pathway for
      patients with dementia, which provides a decision-making framework for how health
      professionals across a range of disciplines deal with patients with dementia who
      drive. CONCLUSIONS: By integrating the latest guidance from diverse roles within
      older people's health services and key experts in the field, the resulting
      pathway reflects up-to-date policy and encompasses differing perspectives and
      good practice. It is potentially a generalisable pathway that can be easily
      adaptable for use internationally, by replacing UK legislation for local
      regulations. A limitation of this pathway is that it does not address the concern
      of mild cognitive impairment and how this condition relates to driving safety.

PMID- 24865642
TI  - Short-term malaria reduction by single-dose azithromycin during mass drug
      administration for trachoma, Tanzania.
AB  - Single-dose mass drug administration of azithromycin (AZT) is underway to
      eliminate trachoma worldwide. Studies in Ethiopia showed a reduction in all-cause
      childhood deaths after administration. To examine the effect of single-dose AZ
      MDA on prevalent malaria infections in a large prospective cohort of children and
      parents in Dodoma Province, Tanzania, we quantified the temporal prevalence of
      malaria parasitemia by real-time PCR for 6 months after single-dose AZT. In the
      first month after treatment but not in subsequent months, Plasmodium falciparum
      infections were reduced by 73% (95% CI 43%-89%) in treatment versus control
      villages and differences remained significant (p = 0.00497) in multivariate
      models with village-level random effects. Genetic sequencing of P. falciparum
      ribosomal L4 protein showed no mutations associated with AZT resistance. AZT mass
      drug administration caused a transient, 1-month antimalarial effect without
      selecting for P. falciparum ribosomal L4 resistance mutations in a region with a
      10-year history of treating trachoma with this drug. 

PMID- 24865644
TI  - O-GlcNAcylation is increased in prostate cancer tissues and enhances malignancy
      of prostate cancer cells.
AB  - O-GlcNAc is an O-linked ?-N-acetylglucosamine moiety attached to the side-chain
      hydroxyl of a serine or threonine residue in numerous cytoplasmic and nuclear
      proteins. In this study, we detected the level of O-GlcNAc in prostate, liver and
      pancreatic cancer tissues, and found that the global O-GlcNAc modification also
      known as O-GlcNAcylation, is specifically increased in prostate cancer tissues
      compared to corresponding adjacent tissues. In addition, we found that global O
      GlcNAcylation is increased in prostate cancer cells and not in benign prostatic
      hyperplasia (BPH) epithelial cells. O-GlcNAc enhanced the anchorage-independent
      growth and the migratory/invasive ability of prostate cancer cells. More
      importantly, we provide here, for the first time to the best of our knowledge,
      direct evidence that increased O-GlcNAcylation induces malignant transformation
      of nontumorigenic (BPH) cells. Furthermore, our study suggested that inhibiting
      the formation of the E-cadherin/catenin/cytoskeleton complex may underly the O
      GlcNAc-induced prostate cancer progression. Overall, these findings indicated
      that O-GlcNAcylation is increased in prostate, but not in liver and pancreatic
      cancer tissues, and that O-GlcNAc can enhance the malignancy of prostate cancer
      cells. 

PMID- 24865646
TI  - Measuring Mitochondrial Function in Permeabilized Cells Using the Seahorse XF
      Analyzer or a Clark-Type Oxygen Electrode.
AB  - Measurements of mitochondrial respiration in intact cells can help define
      metabolism and its dysregulation in fields such as cancer, metabolic disease,
      immunology, and neurodegeneration. Although cells can be offered various
      substrates in the assay medium, many cell types can oxidize stored pools of
      energy substrates. A general bioenergetic profile can therefore be obtained using
      intact cells, but the inability to control substrate provision to the
      mitochondria can restrict an in-depth, mechanistic understanding. Mitochondria
      can be isolated from intact cells, but the yield and quality of the end product
      is often poor and prone to subselection during isolation. Plasma membrane
      permeabilization of cells provides a solution to this challenge, allowing
      experimental control of the medium surrounding the mitochondria. This unit
      describes techniques to measure respiration in permeabilized adherent cells using
      a Seahorse XF Analyzer or permeabilized suspended cells in a Hansatech Oxygraph.

PMID- 24865647
TI  - Assessment of fatty acid beta oxidation in cells and isolated mitochondria.
AB  - Fatty acid beta oxidation is a major pathway of energy metabolism and occurs
      primarily in mitochondria. Drug-induced modulation of this pathway can cause
      adverse effects such as liver injury, or be beneficial for treating heart
      failure, type 2 diabetes, and obesity. Hence, in vitro assays that are able to
      identify compounds that affect fatty acid oxidation are of value for toxicity
      assessments, as well as for efficacy assessments. Here, we describe two high
      throughput assays, one for assessing fatty acid oxidation in cells and the other
      for assessing fatty acid oxidation in isolated rat liver mitochondria. Both
      assays measure fatty acid-driven oxygen consumption and can be used for rapid and
      robust screening of compounds that modulate fatty acid oxidation.

PMID- 24865645
TI  - Synaptic structure quantification in cultured neurons.
AB  - Behavioral problems (e.g., learning and memory) following developmental exposure
      to toxicants suggests that dysregulation of the process of synapse formation and
      function may occur. The ability to assess these changes is thus of value. This
      unit describes a method to investigate toxicant-induced changes to synaptic
      structure formation in primary hippocampal neurons using immunocytochemical
      labeling of the pre- and post-synaptic markers synaptophysin and PSD-95, confocal
      imaging, and three-dimensional object analysis. Protocols for the long-term
      culturing of primary hippocampal neurons and of primary cortical astrocytes, as
      well as their co-culture, are included. While the described methods focus on how
      astrocytes influence synapse formation and how toxicants may interfere in this
      process, modifications to the experimental plan can easily be implemented. This
      would allow for the investigation of the effects of toxicants after treating
      neurons alone, or both astrocytes and neurons in co-culture. With the common
      endpoint of synapse structure formation, differences between varying treatment
      paradigms can expand the understanding of the influence of particular toxicants
      on these diverse cell types and provide insight into potential mechanisms of
      effect and the contributions of each to synapse formation.

PMID- 24865648
TI  - Identifying Compounds that Induce Opening of the Mitochondrial Permeability
      Transition Pore in Isolated Rat Liver Mitochondria.
AB  - The mitochondrial permeability transition pore (MPTP) is a protein pore that
      forms in the inner mitochondrial membrane and allows the membrane to be permeable
      to all molecules of less than 1500 Da. Ca(2+), numerous reactive chemicals, and
      oxidative stress induce MPTP opening, whereas cyclosporin A (CsA) or bongkrekic
      acid block it. In addition, several drugs have been shown to induce MPTP opening,
      leading to the loss of mitochondrial membrane potential, swelling of the matrix
      because of water accumulation, rupture of the outer mitochondrial membrane, and
      release of intermembrane space proteins into the cytosol. This ultimately leads
      to the rupture of the outer mitochondrial membrane and cell demise. Here, we
      describe an assay using isolated rat liver mitochondria that can detect Ca(2+)
      dependent drug-induced opening of the MPTP, providing protocols for screening in
      both cuvette and 96-well format.

PMID- 24865650
TI  - Vertical stratification of the nutritional value of fruit: macronutrients and
      condensed tannins.
AB  - Competing successfully for the best feeding sites is an important behavioral
      strategy but little is known about how feeding sites vary nutritionally within a
      fruit tree. To answer this question we tested how the nutritional value of a
      fruit is influenced by its ripeness and its height within the tree crown. A
      complementary objective was to assess the nutritional value of the midripe fruit,
      a food item rarely mentioned in the literature despite being exploited on a daily
      basis by many frugivores. We measured how the dry weight of pulp, water content,
      and concentration of macronutrients and condensed tannins varied within the tree
      crowns of 15 fruit species. Collections occurred early in the fruiting cycle, so
      as to assess the amount of food in the tree before its exploitation by primates.
      We found that (1) the upper crown produced fruit densities 4.2 times higher, and
      a fruit crop 4.8 times larger, than the lower crown of the same tree; (2)
      considering only midripe and ripe stages, upper-crown fruits contained 28.6% more
      dry pulp, 21.1% more water, and 13.5% more sugars per dry matter than lower-crown
      fruits of the same tree; (3) midripe fruits contained 80% of the concentrations
      of sugars of ripe fruits, making them a sweeter food item than one would expect
      from the intermediate color of their epidermis; (4) cellulose, hemicellulose,
      proteins, and ash proportionally decreased in concentration while dry pulp and
      sugars increased during ripening; and (5) ripe fruits were usually rare in the
      tree (<0.5% of all fruit available) compared to midripe fruits (3-8%). Overall,
      upper-crown feeding sites produced a higher density and quality of food than
      lower-crown sites of the same tree. Our data therefore provide a clear
      nutritional explanation for why tree-feeding frugivores compete for the highest
      feeding sites.

PMID- 24865655
TI  - Study of metabolite differences of flue-cured tobacco from different regions
      using a pseudotargeted gas chromatography with mass spectrometry selected-ion
      monitoring method.
AB  - A pseudotargeted method based on gas chromatography and mass spectrometry with
      selected-ion monitoring was established to investigate the metabolite differences
      of flue-cured tobacco from three different growing regions. The mixed solvent of
      acetonitrile/isopropanol/water (3:3:2, v/v/v) was chosen as the optimal
      extraction system based on the good repeatability and extraction efficiency. A
      self-developed software coupled with commercial software was used to establish
      the pseudotargeted method including 289 peaks and 47 groups. Multivariable
      statistical analysis indicated that tobacco samples can be obviously separated
      based on the geographical origins. On the basis of a Mann-Whitney U test, organic
      acids, phenols, and alkaloids had higher levels in Hunan province. In contrast, a
      large proportion of amino acids (including L-tyrosine, L-proline, and serine),
      sucrose, and linoleic acid were the highest in Yunnan province. Meanwhile,
      multiple metabolic pathways (including carbohydrate metabolism, tricarboxylic
      acid cycle, and nitrogen metabolism) were influenced by growing regions. Twenty
      eight differential metabolites, which had great contributions to the
      classification of tobacco samples of three growing regions, were further defined.
      The results demonstrated that the developed pseudotargeted method was a powerful
      tool to investigate the metabolic profiling of tobacco leaves and discriminate
      tobacco leaves of different growing regions.

PMID- 24865657
TI  - Making non-aqueous high internal phase pickering emulsions: influence of added
      polymer and selective drying.
AB  - We report the first example of a non-aqueous (oil-in-oil) Pickering high internal
      phase emulsion (HIPE) stabilized by chemically modified fumed silica. In this
      case, a 75 vol % ethylene carbonate (EC)-rich internal phase is emulsified in 25
      vol % p-xylene (xylene)-rich continuous phase using interfacial nanoparticles. It
      is revealed that no phase inversion takes place during the HIPE formation process
      when using the appropriate wettability of solid particles. Incorporating
      polystyrene (PS) into xylene enables one-step formation of PS-filled HIPEs in
      place of a multi-step polymerization of the continuous phase. We observe that the
      size of droplets changes with the addition of PS, and we associate this with the
      change in the viscosity of the continuous xylene-rich phase. Drying the pure HIPE
      results in the selective removal of xylene and coalescence of EC-rich droplets.
      With the PS in the xylene-rich continuous phase, we show that EC-rich droplets
      can be retained even though the xylene is evaporated off, and a new semi-solid
      composite containing both liquid phase and solid phase is formed via this non
      aqueous Pickering-HIPE template. 

PMID- 24865652
TI  - The yrpAB operon of Yersinia ruckeri encoding two putative U32 peptidases is
      involved in virulence and induced under microaerobic conditions.
AB  - In an attempt to dissect the virulence mechanisms of Yersinia ruckeri two
      adjacent genes, yrpA and yrpB, encoding putative peptidases belonging to the U32
      family, were analyzed. Similar genes, with the same genetic organization were
      identified in genomic analysis of human-pathogenic yersiniae. RT-PCR studies
      indicated that these genes form an operon in Y. ruckeri. Transcriptional studies
      using an yrpB::lacZY fusion showed high levels of expression of these genes in
      the presence of peptone in the culture medium, as well as under oxygen-limited
      conditions. These two factors had a synergic effect on gene induction when both
      were present simultaneously during bacterial incubation, which indicates the
      important role that environmental conditions in the fish gut can play in the
      regulation of specific genes. LD 50 experiments using an yrpA insertional mutant
      strain demonstrated the participation of this gene in the virulence of Y.
      ruckeri. 

PMID- 24865659
TI  - Enhanced extinction of contextual fear conditioning in ClockDelta19 mutant mice.
AB  - Clock genes have been implicated in several disorders, such as schizophrenia,
      bipolar disorder, autism spectrum disorders, and drug dependence. However, few
      studies to date have examined the role of clock genes in fear-related behaviors.
      The authors used mice with the ClockDelta19 mutation to assess the involvement of
      this gene in contextual fear conditioning. Male wild-type (WT) and ClockDelta19
      mutant mice underwent a single session of contextual fear conditioning (12 min, 4
      unsignaled shocks), followed by daily 12-min retention trials. There were no
      differences between mutant and WT mice in the acquisition of contextual fear, and
      WT and mutant mice demonstrated similar freezing during the first retention
      session. However, extinction of contextual fear was accelerated in mutant mice
      across the remaining retention sessions, as compared to WT mice, suggesting a
      role for Clock in extinction following aversive learning. Because the
      ClockDelta19 mutation has previously been demonstrated to result in an increase
      in dopamine signaling, the authors confirmed the role of dopamine in extinction
      learning using preretention session administration of a low dose of the dopamine
      transport reuptake inhibitor modafinil (0.75 mg/kg), which resulted in decreased
      freezing across retention sessions. These findings are consistent with an
      emerging portrayal of the importance of Clock genes in noncircadian functions, as
      well as the important role of dopamine in extinction learning.

PMID- 24865662
TI  - Multinuclear complex formation between Ca(II) and gluconate ions in hyperalkaline
      solutions.
AB  - Alkaline solutions containing polyhydroxy carboxylates and Ca(II) are typical in
      cementitious radioactive waste repositories. Gluconate (Gluc(-)) is a structural
      and functional representative of these sugar carboxylates. In the current study,
      the structure and equilibria of complexes forming in such strongly alkaline
      solutions containing Ca(2+) and gluconate have been studied. It was found that
      Gluc(-) significantly increases the solubility of portlandite (Ca(OH)2(s)) under
      these conditions and Ca(2+) complexes of unexpectedly high stability are formed.
      The mononuclear (CaGluc(+) and [CaGlucOH](0)) complexes were found to be minor
      species, and predominant multinuclear complexes were identified. The formation of
      the neutral [Ca2Gluc(OH)3](0) (log beta213 = 8.03) and [Ca3Gluc2(OH)4](0) (log
      beta324 = 12.39) has been proven via H2/Pt-electrode potentiometric measurements
      and was confirmed via XAS, (1)H NMR, ESI-MS, conductometry, and freezing-point
      depression experiments. The binding sites of Gluc(-) were identified from
      multinuclear NMR measurements. Besides the carboxylate group, the O atoms on the
      second and third carbon atoms were proved to be the most probable sites for
      Ca(2+) binding. The suggested structure of the trinuclear complex was deduced
      from ab initio calculations. These observations are of relevance in the
      thermodynamic modeling of radioactive waste repositories, where the predominance
      of the binuclear Ca(2+) complex, which is a precursor of various high-stability
      ternary complexes with actinides, is demonstrated. 

PMID- 24865661
TI  - Airway wall area derived from 3-dimensional computed tomography analysis differs
      among lung lobes in male smokers.
AB  - BACKGROUND: It is time-consuming to obtain the square root of airway wall area of
      the hypothetical airway with an internal perimeter of 10 mm (?Aaw at Pi10), a
      comparable index of airway dimensions in chronic obstructive pulmonary disease
      (COPD), from all airways of the whole lungs using 3-dimensional computed
      tomography (CT) analysis. We hypothesized that ?Aaw at Pi10 differs among the
      five lung lobes and ?Aaw at Pi10 derived from one certain lung lobe has a high
      level of agreement with that derived from the whole lungs in smokers. METHODS:
      Pulmonary function tests and chest volumetric CTs were performed in 157 male
      smokers (102 COPD, 55 non-COPD). All visible bronchial segments from the 3rd to
      5th generations were segmented and measured using commercially available 3
      dimensional CT analysis software. ?Aaw at Pi10 of each lung lobe was estimated
      from all measurable bronchial segments of that lobe. RESULTS: Using a mixed
      effects model, ?Aaw at Pi10 differed significantly among the five lung lobes
      (R(2) = 0.78, P<0.0001). The Bland-Altman plots show that ?Aaw at Pi10 derived
      from the right or left upper lobe had a high level of agreement with that derived
      from the whole lungs, while ?Aaw at Pi10 derived from the right or left lower
      lobe did not. CONCLUSION: In male smokers, CT-derived airway wall area differs
      among the five lung lobes, and airway wall area derived from the right or left
      upper lobe is representative of the whole lungs.

PMID- 24865663
TI  - Facile synthesis of gold-silver alloy nanoparticles for application in metal
      enhanced bioluminescence.
AB  - In the present study we explored metal enhanced bioluminescence in luciferase
      enzymes for the first time. For this purpose a simple and reproducible one pot
      synthesis of gold-silver alloy nanoparticles was developed. By changing the molar
      ratio of tri-sodium citrate and silver nitrate we could synthesize spherical Au
      Ag colloids of sizes ranging from 10 to 50 nm with a wide range of localized
      surface plasmon resonance (LSPR) peaks (450-550 nm). The optical tunability of
      the Au-Ag colloids enabled their effective use in enhancement of bioluminescence
      in a luminescent bacterium Photobacterium leiognathi and in luciferase enzyme
      systems from fireflies and bacteria. Enhancement of bioluminescence was 250% for
      bacterial cells, 95% for bacterial luciferase and 52% for firefly luciferase
      enzyme. The enhancement may be a result of energy transfer or plasmon induced
      enhancement. Such an increase can lead to higher sensitivity in detection of
      bioluminescent signals with potential applications in bio-analysis. 

PMID- 24865664
TI  - Cholera in the United States, 2001-2011: a reflection of patterns of global
      epidemiology and travel.
AB  - US cholera surveillance offers insight into global and domestic trends. Between
      2001 and 2011, 111 cases were reported to the Centers for Disease Control and
      Prevention. Cholera was associated with international travel in 90 (81%) patients
      and was domestically acquired in 20 (18%) patients; for one patient, information
      was not available. From January 2001 to October 2010, the 42 (47%) travel
      associated cases were associated with travel to Asia. In October 2010, a cholera
      epidemic started in Haiti, soon spreading to the Dominican Republic (Hispaniola).
      From then to December 2011, 40 (83%) of the 48 travel-associated cases were
      associated with travel to Hispaniola. Of 20 patients who acquired cholera
      domestically, 17 (85%) reported seafood consumption; 10 (59%) ate seafood from
      the US Gulf Coast. In summary, an increase in travel-associated US cholera cases
      was associated with epidemic cholera in Hispaniola in 2010-2011. Travel to Asia
      and consumption of Gulf Coast seafood remained important sources of US cholera
      cases.

PMID- 24865669
TI  - Prolonged gonadotropin stimulation for assisted reproductive technology cycles is
      associated with decreased pregnancy rates for all women except for women with
      polycystic ovary syndrome.
AB  - PURPOSE: To determine if etiology of infertility modifies the relationship
      between the duration of ovarian stimulation and success during assisted
      reproductive technology (ART) cycles. METHODS: A prospectively collected database
      was analyzed in an academic infertility practice. Eight hundred and twelve
      infertile women undergoing their initial fresh embryo, non-donor in vitro
      fertilization (IVF) or Intracytoplasmic Sperm Injection ICSI) cycle between
      January 1999 and December 2010 were evaluated. Clinical pregnancy was the main
      outcome measured. RESULTS: Out of 663 cycles resulting in oocyte retrieval, 299
      produced a clinical pregnancy (45.1%). Women who achieved a clinical pregnancy
      had a significantly shorter stimulation length (11.9 vs. 12.1 days, p = 0.047).
      Polycystic ovary syndrome (PCOS) was the only etiology of infertility that was
      significantly associated with a higher chance for clinical pregnancy and was a
      significant confounder for the association of duration and success of treatment.
      Women with 13 days or longer of stimulation had a 34 % lower chance of clinical
      pregnancy as compared to those who had a shorter cycle (OR 0.66, 95% CI:0.46
      0.95) after adjustment for age, ovarian reserve, number of oocytes retrieved,
      embryos transferred and PCOS diagnosis. CONCLUSION: Prolonged duration of
      stimulation is associated with decreased ART success for all couples, except for
      women with PCOS.

PMID- 24865672
TI  - Monascin attenuates oxidative stress-mediated lung inflammation via peroxisome
      proliferator-activated receptor-gamma (PPAR-gamma) and nuclear factor-erythroid 2
      related factor 2 (Nrf-2) modulation.
AB  - We speculated that peroxisome proliferator-activated receptor (PPAR)-gamma
      agonists may modulate the oxidative stress pathway to ameliorate the development
      of airway inflammation. The effect of Monascus-fermented metabolite monascin (MS)
      and rosiglitazone (Rosi) on oxidative stress-induced lung inflammation was
      evaluated. Luciferase assay and DNA binding activity assay were used to point out
      that MS may be a novel PPAR-gamma agonist and nuclear factor-erythroid 2 related
      factor 2 (Nrf-2) activator. We used hydrogen peroxide (H2O2) to induce
      inflammation in lung epithelial cells. MS and Rosi prevented H2O2-induced ROS
      generation in A549 epithelial cells through PPAR-gamma translocation, avoiding
      inflammatory mediator expression via inhibiting nuclear factor (NF)-kappaB
      translocation. The regulatory ability of MS was abolished by siRNA against PPAR
      gamma. MS also elevated antioxidant enzyme expression via Nrf-2 activation. Both
      PPAR-gamma and Nrf-2 might have benefits against lung inflammation. MS regulated
      PPAR-gamma and Nrf-2 to improve lung oxidative inflammation. 

PMID- 24865674
TI  - Testicular swelling due to lymphatic filariasis after brief travel to Haiti.
AB  - After 6 months of a trip to Haiti, a 25-year-old healthy man presented with a 6
      week history of a very slow progressive intermittent bilateral testicular pain
      and swelling. The biopsies in both testicles revealed the presence of a dead
      filarial parasite. Polymerase chain reaction products of the DNA from the biopsy
      were shown to have a 100% identity to Wuchereria bancrofti. Despite being
      uncommon in travelers, this presentation of W. bancrofti highlights the
      possibility of acquiring W. bancrofti during short-term trips to highly endemic
      regions of the world (i.e., Haiti). 

PMID- 24865676
TI  - An evaluation of methods for assessing the quality of case management for
      inpatients with malaria in Benin.
AB  - To improve healthcare quality for hospitalized patients with malaria in Benin, a
      feasible and valid evaluation method is needed. Because observation of inpatients
      is challenging, chart abstraction is an attractive option. However, the quality
      of inpatient charts is unknown. We employed three methods in five hospitals to
      assess 11 signs of malaria and severe disease: 1) chart abstraction (probability
      sample of inpatients), 2) chart abstraction compared to interviews of inpatients
      and health workers (HWs), and 3) abstraction from charts of recently discharged
      inpatients compared to interviews with HWs. Method 1 showed that of 473 malaria
      signs (from 43 charts), 178 (38%, 95% confidence interval 24-51%) were
      documented. Method 2 showed that 96% (45 of 47) of documented signs were valid.
      Method 3 suggests that 65% (36 of 55) of non-documented signs were assessed (but
      not documented) by HWs. Chart abstraction was feasible and documented data were
      valid, but results should be interpreted cautiously in consideration of low
      levels of documentation. 

PMID- 24865678
TI  - Recruiting post-doctoral fellows into global health research: selecting NIH
      Fogarty International Clinical Research Fellows.
AB  - From 2008 to 2012, the National Institutes of Health (NIH) Fogarty International
      Clinical Research Fellows Program (FICRF) provided 1-year mentored research
      training at low- and middle-income country sites for American and international
      post-doctoral health professionals. We examined the FICRF applicant pool,
      proposed research topics, selection process, and characteristics of enrollees to
      assess trends in global health research interest and factors associated with
      applicant competitiveness. The majority (58%) of 67 US and 57 international
      Fellows were women, and 83% of Fellows had medical degrees. Most applicants were
      in clinical fellowships (41%) or residencies (24%). More applicants proposing
      infectious disease projects were supported (59%) than applicants proposing non
      communicable disease (NCD) projects (41%), although projects that combined both
      topic areas were most successful (69%). The numbers of applicants proposing
      research on NCDs and the numbers of these applicants awarded fellowships rose
      dramatically over time. Funding provided to the FICRF varied significantly among
      NIH Institutes and Centers and was strongly associated with the research topics
      awarded. 

PMID- 24865675
TI  - Cryptosporidiosis in HIV/AIDS patients in Kenya: clinical features, epidemiology,
      molecular characterization and antibody responses.
AB  - We investigated the epidemiological and clinical features of cryptosporidiosis,
      the molecular characteristics of infecting species and serum antibody responses
      to three Cryptosporidium-specific antigens in human immunodeficiency virus
      (HIV)/acquired immunodeficiency syndrome (AIDS) patients in Kenya.
      Cryptosporidium was the most prevalent enteric pathogen and was identified in 56
      of 164 (34%) of HIV/AIDS patients, including 25 of 70 (36%) with diarrhea and 31
      of 94 (33%) without diarrhea. Diarrhea in patients exclusively infected with
      Cryptosporidium was significantly associated with the number of children per
      household, contact with animals, and water treatment. Cryptosporidium hominis was
      the most prevalent species and the most prevalent subtype family was Ib. Patients
      without diarrhea had significantly higher serum IgG levels to Chgp15, Chgp40 and
      Cp23, and higher fecal IgA levels to Chgp15 and Chgp40 than those with diarrhea
      suggesting that antibody responses to these antigens may be associated with
      protection from diarrhea and supporting further investigation of these antigens
      as vaccine candidates. 

PMID- 24865679
TI  - Shared sanitation and the prevalence of diarrhea in young children: evidence from
      51 countries, 2001-2011.
AB  - Shared sanitation is defined as unimproved because of concerns that it creates
      unsanitary conditions; this policy is being reconsidered. We assessed whether
      sharing a toilet facility was associated with an increased prevalence of diarrhea
      among children < 5 years of age. We use data from Demographic and Health Surveys
      conducted in 51 countries. Crude and adjusted prevalence ratios (PRs) for
      diarrhea, comparing children from households that used a shared facility with
      children from households that used a non-shared facility, were estimated for each
      country and pooled across countries. Unadjusted PRs varied across countries,
      ranging from 2.15 to 0.65. The pooled PR was 1.09; differences in socioeconomic
      status explained approximately half of this increased prevalence (adjusted PR =
      1.05). Shared sanitation appears to be a risk factor for diarrhea although
      differences in socioeconomic status are important. The heterogeneity across
      countries, however, suggests that the social and economic context is an important
      factor. 

PMID- 24865677
TI  - Safety and immunogenicity of a rederived, live-attenuated dengue virus vaccine in
      healthy adults living in Thailand: a randomized trial.
AB  - Safety and immunogenicity of two formulations of a live-attenuated tetravalent
      dengue virus (TDEN) vaccine produced using rederived master seeds from a
      precursor vaccine were tested against a placebo control in a phase II,
      randomized, double blind trial (NCT00370682). Two doses were administered 6
      months apart to 120 healthy, predominantly flavivirus-primed adults (87.5% and
      97.5% in the two vaccine groups and 92.5% in the placebo group). Symptoms and
      signs reported after vaccination were mild to moderate and transient. There were
      no vaccine-related serious adverse events or dengue cases reported. Asymptomatic,
      low-level viremia (dengue virus type 2 [DENV-2], DENV-3, or DENV-4) was detected
      in 5 of 80 vaccine recipients. One placebo recipient developed a subclinical
      natural DENV-1 infection. All flavivirus-unprimed subjects and at least 97.1% of
      flavivirus-primed subjects were seropositive to antibodies against all four DENV
      types 1 and 3 months post-TDEN dose 2. The TDEN vaccine was immunogenic with an
      acceptable safety profile in flavivirus-primed adults. 

PMID- 24865680
TI  - A cluster randomized controlled trial to reduce childhood diarrhea using hollow
      fiber water filter and/or hygiene-sanitation educational interventions.
AB  - Safe domestic potable water supplies are urgently needed to reduce childhood
      diarrheal disease. In periurban neighborhoods in Cochabamba, Bolivia, we
      conducted a cluster randomized controlled trial to evaluate the efficacy of a
      household-level hollow fiber filter and/or behavior change communication (BCC) on
      water, sanitation, and hygiene (WASH) to reduce the diarrheal disease in children
      less than 5 years of age. In total, 952 households were followed for a period of
      12 weeks post-distribution of the study interventions. Households using Sawyer
      PointONE filters had significantly less diarrheal disease compared with the
      control arm during the intervention period, which was shown by diarrheal
      prevalence ratios of 0.21 (95% confidence interval [95% CI] = 0.15-0.30) for the
      filter arm and 0.27 (95% CI = 0.22-0.34) for the filter and WASH BCC arm. A non
      significant reduction in diarrhea prevalence was reported in the WASH BCC study
      arm households (0.71, 95% CI = 0.59-0.86). 

PMID- 24865681
TI  - Clinical presentation of dengue by serotype and year of epidemic in Martinique.
AB  - During the last decade Martinique experienced four dengue epidemics, each
      characterized by the predominance of 1 or 2 serotypes. In this retrospective
      database analysis, we investigated the relationship between dengue serotype and
      disease severity. Data on dengue were collected from 715 patients (male/female
      ratio 0.87), 14 to 91 years of age (median 35 years) examined in the adult
      emergency department between 2005 and 2010. In this series, DENV-4 infections
      more frequently had a milder clinical presentation. The DENV-2 infections were
      most often secondary infections admitted at the critical phase of dengue illness
      with signs of plasma leakage. The DENV-1 infections were disabling, particularly
      in females, and most often led to disease of intermediate severity, without overt
      plasma leakage. These data were consistent with there being differences in
      virulence between serotypes, regardless of the host's immune status. However,
      secondary DENV-2 infections showed an increased risk of plasma leakage. 

PMID- 24865682
TI  - High frequency of diabetes and impaired fasting glucose in patients with glucose
      6-phosphate dehydrogenase deficiency in the Western brazilian Amazon.
AB  - Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the most common
      human genetic abnormalities, and it has a significant prevalence in the male
      population (X chromosome linked). The purpose of this study was to estimate the
      frequency of impaired fasting glucose and diabetes among G6PD-deficient persons
      in Manaus, Brazil, an area in the Western Brazilian Amazon to which malaria is
      endemic. Glucose-6-phosphate dehydrogenase-deficient males had more impaired
      fasting glucose and diabetes. This feature could be used as a screening tool for
      G6PD-deficient persons who are unable to use primaquine for the radical cure of
      Plasmodium vivax malaria. 

PMID- 24865683
TI  - Neuroauditory toxicity of artemisinin combination therapies-have safety concerns
      been addressed?
AB  - Although artemisinin-based combination therapies (ACTs) are widely viewed as safe
      drugs with a wide therapeutic dose range, concerns about neuroauditory safety of
      artemisinins arose during their development. A decade ago, reviews of human data
      suggested a potential neuro-ototoxic effect, but the validity of these findings
      was questioned. With 5-10 years of programmatic use, emerging artemisinin
      tolerant falciparum malaria in southeast Asia, and the first calls to consider an
      increased dose of artemisinins, we review neuroauditory safety data on ACTs to
      treat uncomplicated falciparum malaria. Fifteen studies reported a neurological
      or auditory assessment. The large heterogeneity of neuro-ototoxic end points and
      assessment methodologies and the descriptive nature of assessments hampered a
      formal meta-analysis and definitive conclusions, but they highlight the
      persistent lack of data from young children. This subgroup is potentially most
      vulnerable to any neuroauditory toxicity because of their development stage,
      increased malaria susceptibility, and repeated ACT exposure in settings lacking
      robust safety monitoring. 

PMID- 24865684
TI  - Burden of dengue infection and disease in a pediatric cohort in urban Sri Lanka.
AB  - Dengue is the most significant arthropod-borne viral infection of humans. Persons
      infected with dengue viruses (DENV) have subclinical or clinically apparent
      infections ranging from undifferentiated fever to dengue hemorrhagic fever/shock
      syndrome. Although recent studies estimated that the Indian subcontinent has the
      greatest burden of DENV infection and disease worldwide, we do not have reliable,
      population-based estimates of the incidence of infection and disease in this
      region. The goal of this study was to follow-up a cohort of 800 children living
      in a heavily urbanized area of Colombo, Sri Lanka to obtain accurate estimates of
      the incidence of DENV infection and disease. Annual blood samples were obtained
      from all children to estimate dengue seroprevalence at enrollment and to identify
      children exposed to new DENV infections during the study year. Blood was also
      obtained from any child in whom fever developed over the course of the study year
      to identify clinically apparent DENV infections. At enrollment, dengue
      seroprevalence was 53.07%, which indicated high transmission in this population.
      Over the study year, the incidence of DENV infection and disease were 8.39 (95%
      confidence interval = 6.56-10.53) and 3.38 (95% confidence interval = 2.24-4.88),
      respectively, per 100 children per year. The ratio of clinically inapparent to
      apparent infections was 1.48. These results will be useful for obtaining more
      accurate estimates of the burden of dengue in the region and for making decisions
      about testing and introduction of vaccines. 

PMID- 24865685
TI  - Molecular detection of adenoviruses, rhabdoviruses, and paramyxoviruses in bats
      from Kenya.
AB  - We screened 217 bats of at least 20 species from 17 locations in Kenya during
      July and August of 2006 for the presence of adenovirus, rhabdovirus, and
      paramyxovirus nucleic acids using generic reverse transcription polymerase chain
      reaction (RT-PCR) and PCR assays. Of 217 bat fecal swabs examined, 4 bats were
      adenovirus DNA-positive, 11 bats were paramyxovirus RNA-positive, and 2 bats were
      rhabdovirus RNA-positive. Three bats were coinfected by two different viruses. By
      sequence comparison and phylogenetic analysis, the Kenya bat paramyxoviruses and
      rhabdoviruses from this study may represent novel viral lineages within their
      respective families; the Kenya bat adenoviruses could not be confirmed as novel,
      because the same region sequences from other known bat adenovirus genomes for
      comparison were lacking. Our study adds to previous evidence that bats carry
      diverse, potentially zoonotic viruses and may be coinfected with more than one
      virus. 

PMID- 24865686
TI  - Mycobacterium tuberculosis isolates from single outpatient clinic in Panama City
      exhibit wide genetic diversity.
AB  - Understanding Mycobacterium tuberculosis biodiversity and transmission is
      significant for tuberculosis control. This short report aimed to determine the
      genetic diversity of M. tuberculosis isolates from an outpatient clinic in Panama
      City. A total of 62 M. tuberculosis isolates were genotyped by 12 loci
      mycobacterial interspersed repetitive units-variable number of tandem repeats
      (MIRU-VNTR) and Spoligotyping. Forty-five (72.6%) of the isolates showed unique
      MIRU-VNTR genotypes, and 13 (21%) of the isolates were grouped into four
      clusters. Four isolates showed polyclonal MIRU-VNTR genotypes. The MIRU-VNTR
      Hunter-Gaston discriminatory index reached 0.988. The Spoligotyping analysis
      revealed 16 M. tuberculosis families, including Latin American-Mediterranean,
      Harlem, and Beijing. These findings suggest a wide genetic diversity of M.
      tuberculosis isolates at one outpatient clinic. A detailed molecular epidemiology
      survey is now warranted, especially following second massive immigration for
      local Panama Canal expansion activities. 

PMID- 24865687
TI  - Cutaneous leishmaniasis in Cuban immigrants to Texas who traveled through the
      Darien Jungle, Panama.
AB  - Cutaneous leishmaniasis is rarely seen in the United States. Four Cuban
      immigrants traveled along the same route at different times from Cuba to Ecuador,
      then northward, including through the Darien Jungle in Panama. These patients had
      chronic ulcerative non-healing skin lesions and were given a diagnosis of
      leishmaniasis. 

PMID- 24865688
TI  - Prevalence of human-active and variant 1 strains of the tick-borne pathogen
      Anaplasma phagocytophilum in hosts and forests of eastern North America.
AB  - Anaplasmosis is an emerging infectious disease caused by infection with the
      bacterium Anaplasma phagocytophilum. In the eastern United States, A.
      phagocytophilum is transmitted to hosts through the bite of the blacklegged tick,
      Ixodes scapularis. We determined the realized reservoir competence of 14 species
      of common vertebrate hosts for ticks by establishing the probability that each
      species transmits two important strains of A. phagocytophilum (A. phagocytophilum
      human-active, which causes human cases, and A. phagocytophilum variant 1, which
      does not) to feeding larval ticks. We also sampled questing nymphal ticks from ~
      150 sites in a single county over 2 years and sampled over 6 years at one
      location. White-footed mice (Peromyscus leucopus) and Eastern chipmunks (Tamias
      striatus) were the most competent reservoirs for infection with the A.
      phagocytophilum human-active strain. Across the county, prevalence in ticks for
      both strains together was 8.3%; ticks were more than two times as likely to be
      infected with A. phagocytophilum human-active as A. phagocytophilum variant 1.

PMID- 24865691
TI  - A novel case of chronic conjunctivitis in a 58-year-old woman caused by
      Raoultella.
AB  - A 58-year-old woman presented to eye emergency with a chronic conjunctivitis
      which was diagnosed by laboratory microbiological testing to be due to the
      environmental pathogen Raoultella planticola. The organism was sensitive to
      Chloramphenicol and the patient made a rapid recovery on these drops. This is the
      first report of this organism infecting the eye. 

PMID- 24865692
TI  - A novel star-shaped poly(carboxylic acid) for resin-modified glass-ionomer
      restoratives.
AB  - We have developed a novel glass-ionomer cement (GIC) system composed of photo
      curable star-shaped poly(acrylic acid-co-itaconic acid)s. These polyacids were
      synthesized via a chain-transfer radical polymerization using a newly synthesized
      multi-arm chain-transfer agent. The star-shaped polyacids showed significantly
      lower viscosities in water as compared to the linear polyacids. Due to the lower
      viscosities, the molecular weight (MW) of the polyacids can be significantly
      increased for enhancing the mechanical strengths while keeping the ease of mixing
      and handling. The effects of MW, GM-tethering ratio, P/L ratio, and aging on the
      compressive properties of the experimental cements were significant. The light
      cured experimental cements showed significantly improved mechanical strengths
      i.e. 49% in yield strength, 41% in modulus, 25% in CS, 20% in DTS, and 36% in FS,
      higher than commercial Fuji II LC. After aging in water for 1 month, the
      compressive strength of the novel light-cured experimental cement reached 343
      MPa, which was 34% and 42% higher than Fuji II and Fuji II LC, respectively. This
      one-month aged experimental cement was also 23% higher than itself after one day
      aging, indicating that aging in water can significantly enhance salt-bridge
      formation for this novel star-shaped polyacid-comprised GIC.

PMID- 24865690
TI  - OsRACK1 is involved in abscisic acid- and H2O2-mediated signaling to regulate
      seed germination in rice (Oryza sativa, L.).
AB  - The receptor for activated C kinase 1 (RACK1) is one member of the most important
      WD repeat-containing family of proteins found in all eukaryotes and is involved
      in multiple signaling pathways. However, compared with the progress in the area
      of mammalian RACK1, our understanding of the functions and molecular mechanisms
      of RACK1 in the regulation of plant growth and development is still in its
      infancy. In the present study, we investigated the roles of rice RACK1A gene
      (OsRACK1A) in controlling seed germination and its molecular mechanisms by
      generating a series of transgenic rice lines, of which OsRACK1A was either over
      expressed or under-expressed. Our results showed that OsRACK1A positively
      regulated seed germination and negatively regulated the responses of seed
      germination to both exogenous ABA and H2O2. Inhibition of ABA biosynthesis had no
      enhancing effect on germination, whereas inhibition of ABA catabolism
      significantly suppressed germination. ABA inhibition on seed germination was
      almost fully recovered by exogenous H2O2 treatment. Quantitative analyses showed
      that endogenous ABA levels were significantly higher and H2O2 levels
      significantly lower in OsRACK1A-down regulated transgenic lines as compared with
      those in wildtype or OsRACK1A-up regulated lines. Quantitative real-time PCR
      analyses showed that the transcript levels of OsRbohs and amylase genes, RAmy1A
      and RAmy3D, were significantly lower in OsRACK1A-down regulated transgenic lines.
      It is concluded that OsRACK1A positively regulates seed germination by
      controlling endogenous levels of ABA and H2O2 and their interaction. 

PMID- 24865694
TI  - Prospective randomised comparison of diagnostic confidence and image quality with
      normal-dose and low-dose CT pulmonary angiography at various body weights.
AB  - OBJECTIVES: To find a threshold body weight (BW) below 100 kg above which
      computed tomography pulmonary angiography (CTPA) using reduced radiation and a
      reduced contrast material (CM) dose provides significantly impaired quality and
      diagnostic confidence compared with standard-dose CTPA. METHODS: In this
      prospectively randomised study of 501 patients with suspected pulmonary embolism
      and BW <100 kg, 246 were allocated into the low-dose group (80 kVp, 75 ml CM) and
      255 into the normal-dose group (100 kVp, 100 ml CM). Contrast-to-noise ratio
      (CNR) in the pulmonary trunk was calculated. Two blinded chest radiologists
      independently evaluated subjective image quality and diagnostic confidence. Data
      were compared between the normal-dose and low-dose groups in five BW subgroups.
      RESULTS: Vessel attenuation did not differ between the normal-dose and low-dose
      groups within each BW subgroup (P = 1.0). The CNR was higher with the normal-dose
      compared with the low-dose protocol (P < 0.006) in all BW subgroups except for
      the 90-99 kg subgroup (P = 0.812). Subjective image quality and diagnostic
      confidence did not differ between CT protocols in all subgroups (P between 0.960
      and 1.0). CONCLUSIONS: Subjective image quality and diagnostic confidence with 80
      kVp CTPA is not different from normal-dose protocol in any BW group up to 100 kg.
      KEY POINTS: * 80 kVp CTPA is safe in patients weighing <100 kg * Reduced
      radiation and iodine dose still provide high vessel attenuation * Image quality
      and diagnostic confidence with low-dose CTPA is good * Diagnostic confidence does
      not deteriorate in obese patients weighing <100 kg.

PMID- 24865693
TI  - The value of diffusion-weighted imaging in the detection of prostate cancer: a
      meta-analysis.
AB  - OBJECTIVES: To evaluate the diagnostic performance of diffusion-weighted imaging
      (DWI) as a single non-invasive method in detecting prostate cancer (PCa) and to
      deduce its clinical utility. METHODS: A systematic literature search was
      performed to identify relevant original studies. Quality of included studies was
      assessed by QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies). Data
      were extracted to calculate sensitivity and specificity as well as running the
      test of heterogeneity and threshold effect. The summary receiver operating
      characteristic (SROC) curve was drawn and area under SROC curve (AUC) served as a
      determination of the diagnostic performance of DWI for the detection of PCa.
      RESULTS: A total of 21 studies were included, with 27 subsets of data available
      for analysis. The pooled sensitivity and specificity with corresponding 95%
      confidence interval (CI) were 0.62 (95% CI 0.61-0.64) and 0.90 (95% CI 0.89
      0.90), respectively. Pooled positive likelihood ratio and negative likelihood
      ratio were 5.83 (95% CI 4.61-7.37) and 0.30 (95% CI 0.23-0.39), respectively. The
      AUC was 0.8991. Significant heterogeneity was observed. There was no notable
      publication bias. CONCLUSIONS: DWI is an informative MRI modality in detecting
      PCa and shows moderately high diagnostic accuracy. General clinical application
      was limited because of the absence of standardized DW-MRI techniques. KEY POINTS:
      * DWI provides incremental information for the detection and evaluation of PCa *
      DWI has moderately high diagnostic accuracy in detecting PCa * Patient condition,
      imaging protocols and study design positively influence diagnostic performance *
      General clinical application requires optimization of image acquisition and
      interpretation.

PMID- 24865695
TI  - Meta-analysis: diagnostic accuracy of coronary CT angiography with prospective
      ECG gating based on step-and-shoot, Flash and volume modes for detection of
      coronary artery disease.
AB  - OBJECTIVES: To investigate the diagnostic performance of coronary computed
      tomographic angiography (CCTA) with prospective electrocardiograph (ECG) gating
      based on step-and-shoot (SAS), Flash and volume imaging modes. METHODS: We
      searched the electronic databases PubMed for all published studies regarding
      CCTA. We used an exact binomial rendition of the bivariate mixed-effects
      regression model developed for synthesis of diagnostic data. RESULTS: A total of
      21,852 segments, 4,851 vessels and 1,375 patients were identified using database
      searches. Patient-level pooled sensitivity was 0.99 (95 % confidence interval
      [CI], 0.98-1.00); specificity was 0.88 (CI, 0.85-0.91). The results showed that
      the sensitivity and specificity for detection of significant stenosis did not
      differ in the three protocols (P = 0.24). No heterogeneity was found at the
      patient level for sensitivity (Q = 26.23; P = 0.12; I (2) = 27.56 % [CI, 0.00
      67.02 %]) and specificity (Q = 19.54; P = 0.42; I (2) = 2.78 % [CI, 0.00-66.26
      %]). CONCLUSIONS: CCTA with prospective ECG gating has similar high diagnostic
      value to rule out CAD in all three presented modes. KEY POINTS: * The accuracy of
      CCTA with different prospective ECG gating is similar * CCTA with prospective ECG
      gating is effective to exclude coronary artery disease * The radiation dose of
      volume mode increases with higher heart rate.

PMID- 24865696
TI  - Determination of optimal intravenous contrast agent iodine dose for the detection
      of liver metastasis at 80-kVp CT.
AB  - OBJECTIVES: To determine the optimal iodine mass (IM) to achieve a 50-HU increase
      in hepatic attenuation for the detection of liver metastasis based on total body
      weight (TBW) or body surface area (BSA) at 80-kVp computed tomography (CT)
      imaging of the liver. METHODS: One-hundred and fifty patients who underwent
      contrast-enhanced CT at 80-kVp were randomised into three groups: 0.5 gI/kg, 0.4
      gI/kg and 0.3 gI/kg. Portal venous phase images were evaluated for hepatic
      parenchymal enhancement (?HU) and visualisation of liver metastasis. Iodine mass
      per BSA (gI/m(2)) calculated in individual patients were evaluated. RESULTS: Mean
      ?HU for the 0.5 gI/kg group (84.2 HU) was higher than in the 0.4 gI/kg (66.1 HU)
      and 0.3 gI/kg (53.7 HU) groups (P < 0.001). Linear correlation equations between
      ?HU and IM per TBW or BSA are ?HU = 7.0 + 153.0 * IM/TBW (r = 0.73, P < 0.001)
      and ?HU = 11.4 + 4.0 * IM/BSA (r = 0.75, P < 0.001), respectively. The three
      groups were comparable for the visualisation of hepatic metastases. CONCLUSIONS:
      The iodine mass to achieve a 50-HU increase in hepatic attenuation at 80-kVp CT
      was estimated to be 0.28 gI/kg of body weight or 9.6 gI/m(2) of body surface
      area. KEY POINTS: * Hepatic enhancement is expressed as ?HU = 7.0 + 153.0 * IM
      [g]/TBW [kg]. * Hepatic enhancement is expressed as ?HU = 11.4 + 4.0 * IM [g]/BSA
      [m(2)]. * Essential iodine dose at 80-kVp CT was 0.28 gI/kg or 9.6 gI/m(2).

PMID- 24865698
TI  - Does Gadoxetic acid-enhanced 3.0T MRI in addition to 64-detector-row contrast
      enhanced CT provide better diagnostic performance and change the therapeutic
      strategy for the preoperative evaluation of colorectal liver metastases?
AB  - OBJECTIVES: To compare diagnostic performance in the detection of colorectal
      liver metastases between 64-detector-row contrast-enhanced CT (CE-CT) alone and
      the combination of CE-CT and gadoxetic acid-enhanced MRI (EOB-MRI) at 3.0T, and
      to assess whether EOB-MRI in addition to CE-CT results in a change to initially
      planned operative strategy. METHODS: A total of 39 patients (27 men, mean age 65
      years) with 85 histopathologically confirmed liver metastases were included. At
      EOB-MRI, unenhanced (T1- and T2-weighted), dynamic, and hepatocyte-phase images
      were obtained. At CE-CT, four-phase dynamic contrast-enhanced images were
      obtained. One on-site reader and three off-site readers independently reviewed
      both CE-CT alone and the combination of CE-CT and EOB-MRI. Sensitivity, positive
      predictive value, and alternative free-response receiver operating characteristic
      (AFROC) method were calculated. Differences in therapeutic strategy before and
      after the EOB-MRI examination were also evaluated. RESULTS: Sensitivity and area
      under the AFROC curve with the combination of CE-CT and EOB-MRI were
      significantly superior to those with CE-CT alone. Changes in surgical therapy
      were documented in 13 of 39 patients. CONCLUSIONS: The combination of CE-CT and
      EOB-MRI may provide better diagnostic performance than CE-CT alone for the
      detection of colorectal liver metastases, and EOB-MRI in addition to CE-CT
      resulted in changes to the planned operative strategy in one-third of the
      patients. KEY POINTS: * Accurate preoperative imaging is essential for surgical
      planning and successful hepatic resection. * Combination of CE-CT and EOB-MRI is
      useful to detect colorectal liver metastases. * EOB-MRI combined with CE-CT
      contributes to determine the correct therapeutic strategy.

PMID- 24865700
TI  - Selling disease.

PMID- 24865701
TI  - [Many drugs for the elderly--it is dangerous].

PMID- 24865699
TI  - Image quality and cancer visibility of T2-weighted magnetic resonance imaging of
      the prostate at 7 Tesla.
AB  - OBJECTIVES: To assess the image quality of T2-weighted (T2w) magnetic resonance
      imaging of the prostate and the visibility of prostate cancer at 7 Tesla (T).
      MATERIALS & METHODS: Seventeen prostate cancer patients underwent T2w imaging at
      7T with only an external transmit/receive array coil. Three radiologists
      independently scored images for image quality, visibility of anatomical
      structures, and presence of artefacts. Krippendorff's alpha and weighted kappa
      statistics were used to assess inter-observer agreement. Visibility of prostate
      cancer lesions was assessed by directly linking the T2w images to the confirmed
      location of prostate cancer on histopathology. RESULTS: T2w imaging at 7T was
      achievable with 'satisfactory' (3/5) to 'good' (4/5) quality. Visibility of
      anatomical structures was predominantly scored as 'satisfactory' (3/5) and 'good'
      (4/5). If artefacts were present, they were mostly motion artefacts and, to a
      lesser extent, aliasing artefacts and noise. Krippendorff's analysis revealed an
      alpha = 0.44 between three readers for the overall image quality scores.
      Clinically significant cancer lesions in both peripheral zone and transition zone
      were visible at 7T. CONCLUSION: T2w imaging with satisfactory to good quality can
      be routinely acquired, and cancer lesions were visible in patients with prostate
      cancer at 7T using only an external transmit/receive body array coil. KEY POINTS:
      * Satisfactory to good T2-weighted image quality of the prostate is achievable at
      7T. * Periprostatic lipids appear hypo-intense compared to healthy peripheral
      zone tissue at 7T. * Prostate cancer is visible on T2-weighted MRI at 7T.

PMID- 24865702
TI  - [Towards a more specific cancer treatment?].

PMID- 24865707
TI  - [Re: VAS--visual analog scale].

PMID- 24865708
TI  - [Re: Structured electronic health records].

PMID- 24865709
TI  - [R. Bjugn and colleagues reply].

PMID- 24865712
TI  - [Re: It sits between your ears?].

PMID- 24865713
TI  - [Re: It sits between your ears?].

PMID- 24865714
TI  - [Re: A man in his 30s with urethral discharge and dysuria].

PMID- 24865715
TI  - [Re: Excessive belief in suicide risk assessments?].

PMID- 24865717
TI  - [F. Becker replies].

PMID- 24865716
TI  - [Hagen and colleagues reply].

PMID- 24865719
TI  - [E. Helskog and colleagues reply].

PMID- 24865720
TI  - [Re: Medical findings in an interdisciplinary geriatric outpatient clinic
      specialising in falls].

PMID- 24865721
TI  - [Mellingsaeter replies].

PMID- 24865722
TI  - [Re: PSA measurement and prostate cancer--overdiagnosis and overtreatment?].

PMID- 24865723
TI  - [Re: Vitamin D--how much is enough, and is more better for your health?].

PMID- 24865724
TI  - [Professional answers and ethical issues in non-invasive prenatal tests].

PMID- 24865725
TI  - [The animal welfare act should be expanded to include children].

PMID- 24865726
TI  - Oral appliance therapy for sleep apnoea.

PMID- 24865728
TI  - [Drug-drug interactions in nursing home patients].
AB  - BACKGROUND: Patients in nursing homes are often treated with many drugs
      concurrently (polypharmacy), which increases the risk of drug-drug interactions.
      The purpose of this study was to assess the incidence of such interactions in
      nursing home patients. MATERIAL AND METHOD: The study was based on medication
      lists collected from all nursing home patients in Trondheim Municipality in the
      course of one day in 2010. Data from the medication lists was linked to the
      Norwegian interaction database, Druid. RESULTS: The study included 1241 nursing
      home patients. Patients used an average of 9.8 drugs regularly or as needed, with
      a variation of from 0 to 30. In all, 15 patients (1.2%) used drug combinations
      that are classified in Druid as "should not be combined", while 592 (47.7%) used
      combinations classified as "take precautions". There was a clear relationship
      between the number of drugs prescribed and the risk of interactions. The three
      most common drug combinations in the group "should not be combined" were warfarin
      and non-steroidal anti-inflammatory drugs, clopidogrel and proton pump
      inhibitors, and anti-Parkinson medication and dopamine antagonists. CONCLUSION:
      The incidence of serious drug-drug interactions among nursing home patients in
      Trondheim Municipality is low. Polypharmacy is widespread, and the incidence of
      drug interactions where precautions should be taken is high. As nursing home
      patients are a vulnerable group with respect to drug interactions, the risk of
      interactions should be carefully considered when treatment with a new drug is
      started.

PMID- 24865729
TI  - Surgical treatment of epiphrenic oesophageal diverticulum.
AB  - BACKGROUND: Epiphrenic diverticula occur in the lowermost 10 cm of the
      oesophagus. The main symptoms are dysphagia, regurgitation and pain when
      swallowing food. The main purpose of the survey was to evaluate the department's
      results for surgical treatment of this rare and distressing condition. MATERIAL
      AND METHOD: In the period 2002-2012, eleven patients (nine men) underwent surgery
      for an oesophageal diverticulum consisting of excision (n = 8), myotomy of the
      lower oesophageal sphincter and Dor fundoplication (n = 2) or all these
      procedures (n = 1). Two of them were transferred from other hospitals because of
      complications. Details of pre-operative symptoms and post-operative complications
      were retrieved retrospectively from patient records. Ten patients who agreed to
      take part in a retrospective survey responded to a questionnaire a median of 27.5
      months (range of 2-105 months) after surgery. RESULTS: There were no fatalities
      as a result of the treatment. Three patients developed leakage after the
      diverticulum excision, two of whom required reoperation. The patients experienced
      considerable symptomatic improvement. According to the retrospective survey,
      eight of the nine patients with pre-operative dysphagia no longer had it. Four of
      seven with regurgitation, and all five patients who experienced pain in
      connection with swallowing, experienced post-operative improvement. The patients
      reported their condition as completely well (n = 5) or improved (n = 5) after the
      operation. One patient who had undergone reoperation for leakage and oesophageal
      mediastinal fistula did not consent to further surgery. INTERPRETATION: Most
      patients who underwent surgery for epiphrenic oesophageal diverticulum in our
      department experienced symptomatic improvement after surgery.

PMID- 24865730
TI  - [Acute promyelocytic leukaemia].
AB  - BACKGROUND: Acute promyelocytic leukaemia (APL) is a subtype of acute myeloid
      leukaemia (AML) with unique biological and clinical features and unique
      therapeutic requirements. The article provides a brief description of the
      development, pathophysiology, diagnosis and treatment of APL. METHOD: The article
      is based on the authors' own experience and reviews of key articles and national
      and international guidelines. RESULTS: The disease is caused by a single genetic
      event, namely the translocation t(15;17), which gives rise to the oncoprotein PML
      RARA. Clinical and morphological characteristics arouse suspicion of the disease,
      and the diagnosis is verified by detecting the translocation. At the time of
      diagnosis most patients have severe coagulopathy and the predominant clinical
      manifestation is bleeding. Early mortality is due to severe haemorrhage, usually
      intracranial. Early treatment start with all-trans retinoic acid (ATRA) on
      suspicion of APL is essential to reduce this early mortality. ATRA is also an
      important part of continued treatment, in combination with anthracycline-based
      chemotherapy and possibly arsenic. After this treatment, the prognosis for
      disease-free long-term survival is > 90%. There are also safe and effective
      treatment options for elderly patients with complex comorbidities.
      INTERPRETATION: With APL it is particularly important to start disease-targeting
      therapy in the form of ATRA quickly because of the high risk of serious
      haemorrhages and high early mortality. If serious haemorrhages are avoided, the
      prognosis is very good.

PMID- 24865731
TI  - Ectopic thyroid.

PMID- 24865732
TI  - [A man in his 80s with muscle stiffness and skin bleeding].

PMID- 24865746
TI  - [Cardiac resynchronization therapy in heart failure--Norwegian guidelines].

PMID- 24865748
TI  - Hospitals don't miss codeine after it's gone.

PMID- 24865749
TI  - New antiplatelet agent approved.

PMID- 24865750
TI  - CMS chief affirms incident-to billing for pharmacists is allowed.

PMID- 24865751
TI  - Integrating medication management information into the online formulary at a
      tertiary academic medical center.

PMID- 24865752
TI  - A pharmacy concierge service to optimize fidaxomicin therapy.

PMID- 24865753
TI  - Calcium and magnesium for oxaliplatin-induced neuropathy.

PMID- 24865754
TI  - Advanced clinical pharmacy services in a nonacademic community hospital.

PMID- 24865756
TI  - An academia rotation during a postgraduate year 2 residency.

PMID- 24865755
TI  - Clinical knowledge management: Using Extensible Markup Language to characterize
      clinical decision support.

PMID- 24865757
TI  - Lomitapide: A novel agent for the treatment of homozygous familial
      hypercholesterolemia.
AB  - PURPOSE: The pharmacology, pharmacokinetics, and clinical efficacy and safety of
      lomitapide in the management of homozygous familial hypercholesterolemia (HoFH)
      are reviewed. SUMMARY: Lomitapide (Juxtapid, Aegerion Pharmaceuticals) is an oral
      microsomal triglyceride transfer protein (MTP) inhibitor indicated for the
      treatment of patients with HoFH, a rare form of hypercholesterolemia that can
      lead to premature atherosclerotic disease. In clinical trials, the use of
      lomitapide alone or in combination with other lipid-lowering modalities reduced
      plasma concentrations of low-density lipoprotein cholesterol (LDL-C) by a mean of
      more than 50%. Lomitapide is associated with significant gastrointestinal adverse
      effects and increases in hepatic fat levels. Lomitapide undergoes hepatic
      metabolism via cytochrome P-450 (CYP) isoenzyme 3A4 and interacts with CYP3A4
      substrates including atorvastatin and simvastatin; dose adjustment is recommended
      when lomitapide is used concurrently with these agents. In patients receiving
      concomitant warfarin, the International Normalized Ratio (INR) should be closely
      monitored, as lomitapide use may increase INR values. The recommended initial
      dosage of lomitapide is 5 mg once daily, with subsequent upward dose adjustment
      at specified intervals according to tolerability. Lomitapide is contraindicated
      in patients with moderate-to-severe liver disease, patients with sustained
      abnormal liver function tests, patients taking strong or moderate CYP3A4
      inhibitors, and pregnant patients. CONCLUSION: Lomitapide is an oral MTP
      inhibitor approved for the treatment of HoFH. This agent appears to be a
      realistic option for patients with HoFH who are unable to attain their LDL-C goal
      or cannot tolerate statin therapy.

PMID- 24865758
TI  - Implications of using Cockcroft-Gault and Modification of Diet in Renal Disease
      Study equations to estimate renal function in ethnic Korean patients.
AB  - PURPOSE: Variations in renal function calculations performed with different
      estimating equations were investigated using data on a large nationally
      representative sample of Korean adults. METHODS: A retrospective, cross
      sectional, population-based analysis was conducted using 2007-09 data from the
      Korea National Health and Nutrition Examination Survey. Estimated creatinine
      clearance (CIcr) values for the study sample (n = 16,002) were calculated using
      the Cockcroft-Gault (CG) formula, and glomerular filtration rate estimates were
      performed using the four-variable Modification of Diet in Renal Disease (MDRD)
      Study equation, with normalization of values for body surface area. Renal
      function estimates derived from the CG and MDRD equations were compared among
      subgroups; rates of disagreement in the categorization of subjects for medication
      dose adjustments according to widely used CIcr cutoff values were analyzed.
      RESULTS: In the study sample as a whole and all evaluated subgroups, renal
      function estimates performed via the CG and MDRD equations differed significantly
      (p < 0.001); the greatest differences were seen in calculated values for the
      elderly, patients with diabetes, and those with a body mass index of >=25 kg/m(2)
      or a serum creatinine concentration of <1 mg/dL. Maximum rates of disagreement in
      dosage-adjustment categorizations by the CG and MDRD equations were observed at
      the highest CLcr cutoff values and ranged from 6.7% to nearly 20%. CONCLUSION:
      The study revealed disagreements in renal function estimates performed using CG
      and MDRD equations in a large sample of ethnic Korean adults, with more
      pronounced differences observed in certain subgroups.

PMID- 24865759
TI  - Evaluation of dedicated infectious diseases pharmacists on antimicrobial
      stewardship teams.
AB  - PURPOSE: Patient care improvements and cost savings achieved by a large
      integrated health system through the implementation of antimicrobial stewardship
      programs (ASPs) at two hospitals are reported. METHODS: A pre-post analysis was
      conducted to evaluate cost and quality outcomes at the two ASP sites and three
      similar sites within the same health system not included in the ASP initiative.
      The utilization of 15 targeted antimicrobials and associated costs at the five
      sites during designated preimplementation and postimplementation periods were
      compared; changes in Hospital Standardized Mortality Ratio (HSMR) values for
      specific infections among Medicare patients were also assessed. RESULTS: In the
      year after ASP implementation, aggregate direct antimicrobial acquisition costs
      at the two study sites decreased 17.3% from prior-year levels and increased by
      9.1% at the three comparator sites. Significant decreases in the consumption of
      targeted antimicrobial classes (antipseudomonals, quinolones, and agents active
      against methicillin-resistant Staphylococcus aureus) were observed at the ASP
      sites. Among the 2446 ASP interventions recorded, 72% involved discontinuing or
      narrowing the use of broad-spectrum antimicrobials. Although rates of health care
      associated Clostridium difficile infection were little changed at both study
      sites after ASP implementation, HSMR data indicated substantial gains in
      combating sepsis and C. difficile and respiratory infections. CONCLUSION: After
      implementation of ASPs at two study sites, the utilization of all classes of
      antibiotics decreased and antimicrobial costs per 1000 patient-days decreased.
      While HSMR values for sepsis (including C. difficile-associated cases) and
      respiratory infections improved, the rate of C. difficile infections stayed the
      same.

PMID- 24865760
TI  - Comparison of three generic vancomycin products using liquid chromatography-mass
      spectrometry and an online tool.
AB  - PURPOSE: Three different generic vancomycin products were compared using liquid
      chromatography-mass spectrometry (LC-MS) and open-access metabolomic tools.
      METHODS: Single-lot samples of vancomycin hydrochloride from three different
      manufacturers (Hospira, APP Pharmaceuticals, and Pfizer) were reconstituted and
      injected into a high-resolution LC-MS system. The mass spectral fingerprints were
      compared for similarity of nonvancomycin B components using the XCMS Online
      system through Scripps University. Significance was defined as a p of <=0.01 and
      a fold change of >=1.5. The concentration of vancomycin B in each product was
      also measured using LC-MS on days 0, 1, 2, 4, 7, 10, and 14. RESULTS: Qualitative
      comparisons of the products using the XCMS Online interface indicated the
      presence of significant differences among the products at the time of
      reconstitution; however, these variations seemed to converge after 14 days of
      storage. The concentration profiles of vancomycin B during refrigerated storage
      did not differ significantly among the three products. XCMS Online analyses
      revealed that the Pfizer and Hospira products were the most similar to each
      other. CONCLUSION: While there were no significant differences found in the
      concentration of vancomycin B among Pfizer, APP, and Hospira products, there were
      differences in their initial mass spectral analysis after reconstitution. Liquid
      chromatography-tandem mass spectrometry profiles of the ions or isotopes present
      in the three products showed significant differences in impurities such as
      crystalline degradation product (CDP)-1 and CDP intermediate. After 14 days of
      refrigerated storage, the differences among the products converged, and fewer
      distinct features could be detected.

PMID- 24865761
TI  - Providing global views to address local challenges.

PMID- 24865762
TI  - Use of and interaction with medical interpreters.

PMID- 24865763
TI  - Report of the ASHP Task Force on Organizational Structure.

PMID- 24865764
TI  - The burden of diabetes mellitus for medicare beneficiaries.
AB  - The objective was to estimate health care costs and utilization for Medicare
      beneficiaries with type 1 (T1DM) or type 2 (T2DM) diabetes and their respective
      matched control cohorts. A retrospective claims cohort analysis was used to
      assess direct health care cost and utilization of health services in 2009 for
      patients aged 65-89 who were enrolled in a Medicare Advantage Plus prescription
      drug plan. Patients were matched 1:1 with patients without diabetes. All-cause
      health care costs for 2009 were calculated as the sum of all medical and pharmacy
      claims. The analysis included 6562 patients with T1DM and an equal number of
      matched controls, and 194,775 patients with T2DM and an equal number of matched
      controls. There were no significant demographic differences between cohorts for
      matched variables. Patients with T2DM had significantly higher mean Deyo/Charlson
      Comorbidity Index scores compared with their controls (2.47 versus 0.77;
      P<0.001), although all groups reported a high rate of costly comorbidities such
      as hypertension and heart disease. Mean all-cause health care costs per patient
      per year were significantly higher for patients with T1DM and T2DM versus
      controls for inpatient hospitalizations; outpatient, office, and emergency room
      visits; pharmacy expenditures; and total health care costs for 2009 (T1DM group:
      $20,701+/-$30,201; T1DM-matched control group: $6,537+/-$10,441; T2DM group:
      $10,437+/-$18,518; T2DM-matched control group: $6,505+/-$11,140). Diabetes
      escalates health care costs for Medicare Advantage Plus patients compared with
      patients in the same plan without diabetes, regardless of comorbidities.

PMID- 24865765
TI  - A rational approach to employing high plasma levels of antipsychotics for
      violence associated with schizophrenia: case vignettes.
AB  - Forensic psychiatric settings contain a high prevalence of treatment-resistant
      violent schizophrenia patients. Clozapine therapy has the most robust data for
      the management of violence in patients with schizophrenia, but for those who
      cannot tolerate or refuse clozapine, high-dose antipsychotic treatment to high
      achieve high plasma levels remains a viable option despite limited evidence for
      efficacy in controlled trials. This article enumerates rational guidelines for
      employing high plasma level strategies, emphasizing the appropriate
      interpretation of, and reaction to high plasma antipsychotic levels in these
      treatment resistant patients, and the need to push treatment to the limits of
      tolerability or clinical response. 

PMID- 24865767
TI  - Electrode spanning with partial tripolar stimulation mode in cochlear implants.
AB  - The perceptual effects of electrode spanning (i.e., the use of nonadjacent return
      electrodes) in partial tripolar (pTP) mode were tested on a main electrode EL8 in
      five cochlear implant (CI) users. Current focusing was controlled by sigma (the
      ratio of current returned within the cochlea), and current steering was
      controlled by alpha (the ratio of current returned to the basal electrode).
      Experiment 1 tested whether asymmetric spanning with alpha = 0.5 can create
      additional channels around standard pTP stimuli. It was found that in general,
      apical spanning (i.e., returning current to EL6 rather than EL7) elicited a pitch
      between those of standard pTP stimuli on main electrodes EL8 and EL9, while basal
      spanning (i.e., returning current to EL10 rather than EL9) elicited a pitch
      between those of standard pTP stimuli on main electrodes EL7 and EL8. The pitch
      increase caused by apical spanning was more salient than the pitch decrease
      caused by basal spanning. To replace the standard pTP channel on the main
      electrode EL8 when EL7 or EL9 is defective, experiment 2 tested asymmetrically
      spanned pTP stimuli with various alpha, and experiment 3 tested symmetrically
      spanned pTP stimuli with various sigma. The results showed that pitch increased
      with decreasing alpha in asymmetric spanning, or with increasing sigma in
      symmetric spanning. Apical spanning with alpha around 0.69 and basal spanning
      with alpha around 0.38 may both elicit a similar pitch as the standard pTP
      stimulus. With the same sigma, the symmetrically spanned pTP stimulus was higher
      in pitch than the standard pTP stimulus. A smaller sigma was thus required for
      symmetric spanning to match the pitch of the standard pTP stimulus. In summary,
      electrode spanning is an effective field-shaping technique that is useful for
      adding spectral channels and handling defective electrodes with CIs. 

PMID- 24865766
TI  - Basilar membrane and tectorial membrane stiffness in the CBA/CaJ mouse.
AB  - The mouse has become an important animal model in understanding cochlear
      function. Structures, such as the tectorial membrane or hair cells, have been
      changed by gene manipulation, and the resulting effect on cochlear function has
      been studied. To contrast those findings, physical properties of the basilar
      membrane (BM) and tectorial membrane (TM) in mice without gene mutation are of
      great importance. Using the hemicochlea of CBA/CaJ mice, we have demonstrated
      that tectorial membrane (TM) and basilar membrane (BM) revealed a stiffness
      gradient along the cochlea. While a simple spring mass resonator predicts the
      change in the characteristic frequency of the BM, the spring mass model does not
      predict the frequency change along the TM. Plateau stiffness values of the TM
      were 0.6 +/- 0.5, 0.2 +/- 0.1, and 0.09 +/- 0.09 N/m for the basal, middle, and
      upper turns, respectively. The BM plateau stiffness values were 3.7 +/- 2.2, 1.2
      +/- 1.2, and 0.5 +/- 0.5 N/m for the basal, middle, and upper turns,
      respectively. Estimations of the TM Young's modulus (in kPa) revealed 24.3 +/-
      25.2 for the basal turns, 5.1 +/- 4.5 for the middle turns, and 1.9 +/- 1.6 for
      the apical turns. Young's modulus determined at the BM pectinate zone was 76.8 +/
      72, 23.9 +/- 30.6, and 9.4 +/- 6.2 kPa for the basal, middle, and apical turns,
      respectively. The reported stiffness values of the CBA/CaJ mouse TM and BM
      provide basic data for the physical properties of its organ of Corti.

PMID- 24865768
TI  - Flos Puerariae extract prevents myocardial apoptosis via attenuation oxidative
      stress in streptozotocin-induced diabetic mice.
AB  - BACKGROUND: Diabetic cardiomyopathy (DCM) suggests a direct cellular insult to
      myocardium. Apoptosis is considered as one of the hallmarks of DCM. Oxidative
      stress plays a key role in the pathogenesis of DCM. In this study, we explored
      the prevention of myocardial apoptosis by crude extract from Flos Puerariae (FPE)
      in experimental diabetic mice. METHODS: Experimental diabetic model was induced
      by intraperitoneally injection of streptozotocin (STZ, 50 mg/kg/day) for five
      consecutive days in C57BL/6J mice. FPE (100, 200 mg/kg) was orally administrated
      once a day for ten weeks. Cardiac structure changes, apoptosis, superoxide
      production, NADPH oxidase subunits expression (gp91phox, p47phox, and p67phox),
      and related regulatory factors were assessed in the heart of mice. RESULTS:
      Diabetic mice were characterized by high blood glucose (>=11.1 mmol/L) and
      reduced body weight. In the end of the experiment, aberrant myofilament
      structure, as well as TUNEL positive cardiac cells coupled with increased Bax/Bcl
      2 ratio and Caspase-3 expression was found in diabetic mice. Moreover, ROS
      formation, the ratio of NADP+/NADPH and NADPH oxidase subunits expression of
      gp91phox and p47phox, lipid peroxidation level was significantly increased, while
      antioxidant enzyme SOD and GSH-Px activity were reduced in the myocardial tissue
      of diabetic mice. In contrast, treatment with FPE resulted in a normalized
      glucose and weight profile. FPE administration also preserved myocardial
      structure and reduced apoptotic cardiac cell death in diabetic mice. The elevated
      markers of oxidative stress were significantly reversed by FPE supplementation.
      Further, FPE treatment markedly inhibited the increased Bax/Bcl-2 ratio and
      Caspase-3 expression, as well as suppressed JNK and P38 MAPK activation in the
      heart of diabetic mice. CONCLUSIONS: Our data demonstrate for the first time that
      FPE may have therapeutic potential for STZ-induced diabetic cardiomyopathy
      through preventing myocardial apoptosis via attenuation oxidative stress. And
      this effect is probably mediated by JNK and P38 MAPK signaling pathway.

PMID- 24865769
TI  - Factors associated with inconsistent condom use in adolescents with negative or
      unknown HIV status in Northwest Cameroon.
AB  - The purpose of this study is to evaluate the association between utilization of
      HIV testing and condom use amongst Cameroonian youths/adolescents who are not
      known to be HIV-infected. Worldwide, HIV is spreading most quickly amongst
      youths/adolescents. Between 44% and 82% of sexually active youths in Cameroon
      report inconsistent condom use. Data regarding utilization of HIV testing and
      condom use are lacking. A cross-sectional survey was administered to 431 youths
      ages 12-26 years in Cameroon from September 2011 to December 2011. Data on
      sociodemographics, sexual risk behaviors, self-reported HIV status, and condom
      use were collected. We compared rates of inconsistent condom use between those
      with known HIV negative status who utilized testing (HIV-N) and those with
      unknown status due to unutilized testing (HIV-U). Inconsistent condom use was
      defined as responding "never," "sometimes," or "usually," while consistent condom
      use was defined as responding "always" to questions regarding frequency of condom
      use. Generalized estimating equations were applied to assess the association
      between HIV testing and inconsistent condom use, adjusting for other confounders.
      Of 414 eligible respondents, 205 were HIV-U and 209 were HIV-N. HIV-U subjects
      were younger (mean age = 16.4 vs. 17.9, p < 0.001) and more likely to report
      living in an urban area (p = 0.002) than HIV-N subjects. Seventy-two percent
      (137/191) of sexually active youths reported inconsistent condom use. After
      adjusting for potential confounders, HIV-U status (odds ratio [OR] = 3.97, 95%
      confidence interval [CI] = 1.68-6.01) was associated with inconsistent condom
      use. Similarly, female gender (OR = 3.2, 95% CI = 1.29-7.89) was associated with
      inconsistent condom use, while older age at sexual debut was associated with a
      decreased risk for inconsistent condom use (OR = 0.67, 95% CI = 0.56-0.81).
      Cameroonian adolescents report high rates of inconsistent condom use which we
      found to be associated with self-reported unknown HIV status due to unutilized
      HIV testing. Successful HIV prevention programs among African youths/adolescents
      may benefit from expanded HIV testing programs. 

PMID- 24865770
TI  - Endovascular treatment of delayed hemorrhage developing after the
      pancreaticoduodenectomy procedure.
AB  - AIM AND BACKGROUND: Delayed hemorrhage after pancreaticoduodenectomy (PD) is
      still one of the most common causes of mortality. However, the case series
      regarding interventional treatment of delayed hemorrhage after PD are limited. In
      this retrospective study, we aimed to evaluate functional outcomes of
      interventional treatment of late hemorrhages developing after PD. MATERIAL AND
      METHODS: We retrospectively evaluated 16 patients who received endovascular
      treatment for delayed arterial hemorrhage after PD procedure. Postsurgical
      nonhemorrhagic complications, time of hemorrhage, site of hemorrhage,
      endovascular treatment technique, postprocedural complications, and mortality
      rates were obtained. RESULTS: Mean duration of delayed hemorrhage after PD was 18
      days. Computed tomography angiography images for the hemorrhage period were
      available for 15 patients. We observed extravasation alone in seven patients and
      pseudoaneurysm alone in five. Pushable coil was used in 15 patients and covered
      stent in 1. Two patients died due to hepatic failure, and one patient died
      because of multiple organ dysfunction syndrome (MODS). CONCLUSIONS: Delayed
      hemorrhage after PD is difficult to identify, but accurate and early diagnosis is
      of vital importance. To date, most appropriate management of this complication
      remains unclear. Although endovascular treatment techniques may vary for every
      patient, it is a reliable and effective method for halting hemorrhage. Therefore,
      interventional procedures must be primarily considered rather than surgical
      interventions.

PMID- 24865771
TI  - Re-analysis of omics data indicates Smithella may degrade alkanes by addition to
      fumarate under methanogenic conditions.

PMID- 24865772
TI  - Role of methylotrophs in the degradation of hydrocarbons during the Deepwater
      Horizon oil spill.
AB  - The role of methylotrophic bacteria in the fate of the oil and gas released into
      the Gulf of Mexico during the Deepwater Horizon oil spill has been controversial,
      particularly in relation to whether organisms such as Methylophaga had
      contributed to the consumption of methane. Whereas methanotrophy remains
      unqualified in these organisms, recent work by our group using DNA-based stable
      isotope probing coupled with cultivation-based methods has uncovered hydrocarbon
      degrading Methylophaga. Recent findings have also shown that methylotrophs,
      including Methylophaga, were in a heightened state of metabolic activity within
      oil plume waters during the active phase of the spill. Taken collectively, these
      findings suggest that members of this group may have participated in the
      degradation of high-molecular-weight hydrocarbons in plume waters. The discovery
      of hydrocarbon-degrading Methylophaga also highlights the importance of
      considering these organisms in playing a role to the fate of oil hydrocarbons at
      oil-impacted sites.

PMID- 24865774
TI  - A reversal of fortunes: climate change 'winners' and 'losers' in Antarctic
      Peninsula penguins.
AB  - Climate change is a major threat to global biodiversity. Antarctic ecosystems are
      no exception. Investigating past species responses to climatic events can
      distinguish natural from anthropogenic impacts. Climate change produces
      'winners', species that benefit from these events and 'losers', species that
      decline or become extinct. Using molecular techniques, we assess the demographic
      history and population structure of Pygoscelis penguins in the Scotia Arc related
      to climate warming after the Last Glacial Maximum (LGM). All three pygoscelid
      penguins responded positively to post-LGM warming by expanding from glacial
      refugia, with those breeding at higher latitudes expanding most. Northern
      (Pygoscelis papua papua) and Southern (Pygoscelis papua ellsworthii) gentoo sub
      species likely diverged during the LGM. Comparing historical responses with the
      literature on current trends, we see Southern gentoo penguins are responding to
      current warming as they did during post-LGM warming, expanding their range
      southwards. Conversely, Adelie and chinstrap penguins are experiencing a
      'reversal of fortunes' as they are now declining in the Antarctic Peninsula, the
      opposite of their response to post-LGM warming. This suggests current climate
      warming has decoupled historic population responses in the Antarctic Peninsula,
      favoring generalist gentoo penguins as climate change 'winners', while Adelie and
      chinstrap penguins have become climate change 'losers'. 

PMID- 24865776
TI  - Near room-temperature multiferroic materials with tunable ferromagnetic and
      electrical properties.
AB  - The quest for multiferroic materials with ferroelectric and ferromagnetic
      properties at room temperature continues to be fuelled by the promise of novel
      devices. Moreover, being able to tune the electrical polarization and the
      paramagnetic-to-ferromagnetic transition temperature constitutes another current
      research direction of fundamental and technological importance. Here we report on
      the first-principles-based prediction of a specific class of materials--namely,
      R2NiMnO6/La2NiMnO6 superlattices where R is a rare-earth ion--that exhibit an
      electrical polarization and strong ferromagnetic order near room temperature, and
      whose electrical and ferromagnetic properties can be tuned by means of chemical
      pressure and/or epitaxial strain. Analysis of the first-principles results
      naturally explains the origins of these highly desired features.

PMID- 24865775
TI  - Immunohistochemical expression of caspase-3, caspase-5, caspase-7 and apoptotic
      protease-activating factor-1 (APAF-1) in the liver and kidney of rats exposed to
      zoledronic acid (ZOL) and basic fibroblast growth factor (bFGF).
AB  - BACKGROUND: Bisphosphonates (BPs) like zoledronic acid (ZOL) are widely used for
      the treatment of different diseases such as osteoporosis, metastatic bone
      diseases and hypercalcaemia. However, the effects of BPs on apoptosis of the
      liver and kidney after treatment are unclear. Furthermore, basic fibroblast
      growth factor (bFGF) is an angiogenic molecule, which plays an important role in
      angiogenesis and tissue repair. The present study investigated the expression of
      caspase-3, -5, -7 and apoptotic protease-activating factor-1 (APAF-1) in the
      liver and kidney of rats treated with ZOL and bFGF. OBJECTIVE: The present study
      investigated the expression of caspase-3, -5, -7 and apoptotic protease
      activating factor-1 (APAF-1) in the liver and kidney of rats treated with ZOL and
      bFGF. ANIMALS AND METHODS: An animal model with 32 male Sprague Dawley rats was
      used. The effects of ZOL and bFGF on liver and kidney with the expressions of
      different apoptosis markers were studied histopathologically and
      immunohistochemically. Data were analyzed using Cronbach's alpha, Kruskal-Wallis
      and Bonnferroni-Dunn tests. RESULTS: The main microscopic findings were
      mononuclear cell infiltrations around the bile ducts, binuclear and markedly
      enlarged hepatocytes (cytomegaly) and mitotic figures in the liver of rats
      treated with ZOL only. Immunohistochemically, both APAF-1 and caspase-3, -5 and 
      7 expressions were found elevated significantly (P < 0.05) in the liver and
      kidney of these rats. CONCLUSIONS: Our findings showed that ZOL treatment
      increased while bFGF treatment decreased apoptosis significantly in the liver and
      kidney of Sprague Dawley rats. CLINICAL IMPORTANCE: The addition of bFGF to ZOL
      treatment of various diseases might reduce the ZOL effects.

PMID- 24865777
TI  - Infliximab maintains durable response and facilitates catch-up growth in luminal
      pediatric Crohn's disease.
AB  - BACKGROUND: Infliximab induces and maintains clinical remission in children with
      Crohn's disease (CD), but specifically pediatric long-term data remain sparse.
      METHODS: Patients (N = 195) who received infliximab +/- immunomodulator for
      luminal CD were retrospectively reviewed. Outcomes included clinical response,
      linear growth, and mucosal healing. Durability of response was assessed using Cox
      proportional hazards models. Levels of infliximab and antibodies (antibodies to
      infliximab) were measured when response was lost. RESULTS: Among 195 patients
      (median age, 13.9 yr; median CD duration, 1.6 yr), 81% experienced complete
      response (judged by physician global assessment and pediatric Crohn's disease
      activity index <=10). Longer duration of diagnosed CD and female gender were
      associated with lower response. During first year of follow-up, 35% of subjects
      had regimen individualized through dose escalation/interval shortening. Despite
      regimen optimization, 16/157 complete responders experienced loss of response at
      a rate of 2% to 6% per year over 5 years, associated with development of
      antibodies to infliximab. Concurrent immunomodulation for >=30 weeks
      significantly decreased loss of response (hazard ratio = 0.25, 95% confidence
      interval, 0.08-0.76; P = 0.014). Follow-up endoscopic examination was performed
      in 40 responders, of whom 22 (73%) demonstrated complete resolution of mucosal
      ulceration. Patients with growth potential (Tanner 1/2 at induction) demonstrated
      significant improvements in mean height z-score from induction to years 1 and 2
      of follow-up (P < 0.001). With infliximab initiation within the first 18 months
      after diagnosis, mean height z-score normalized to 0 after 3 years. CONCLUSIONS:
      These data demonstrate sustained effectiveness of infliximab in children and
      adolescents with luminal CD. Durability of response is increased by concomitant
      immunomodulation. Clinical response is associated with enhanced linear growth,
      particularly when therapy is initiated early.

PMID- 24865773
TI  - Involvement of HDAC1 and HDAC3 in the Pathology of Polyglutamine Disorders:
      Therapeutic Implications for Selective HDAC1/HDAC3 Inhibitors.
AB  - Histone deacetylases (HDACs) enzymes, which affect the acetylation status of
      histones and other important cellular proteins, have been recognized as
      potentially useful therapeutic targets for a broad range of human disorders.
      Emerging studies have demonstrated that different types of HDAC inhibitors show
      beneficial effects in various experimental models of neurological disorders. HDAC
      enzymes comprise a large family of proteins, with18 HDAC enzymes currently
      identified in humans. Hence, an important question for HDAC inhibitor
      therapeutics is which HDAC enzyme(s) is/are important for the amelioration of
      disease phenotypes, as it has become clear that individual HDAC enzymes play
      different biological roles in the brain. This review will discuss evidence
      supporting the involvement of HDAC1 and HDAC3 in polyglutamine disorders,
      including Huntington's disease, and the use of HDAC1- and HDAC3-selective HDAC
      inhibitors as therapeutic intervention for these disorders. Further, while HDAC
      inhibitors are known alter chromatin structure resulting in changes in gene
      transcription, understanding the exact mechanisms responsible for the preclinical
      efficacy of these compounds remains a challenge. The potential chromatin-related
      and non-chromatin-related mechanisms of action of selective HDAC inhibitors will
      also be discussed. 

PMID- 24865778
TI  - Prevalence of a gluten-free diet and improvement of clinical symptoms in patients
      with inflammatory bowel diseases.
AB  - BACKGROUND: Maintaining a gluten-free diet (GFD) without an underlying diagnosis
      of celiac disease has enjoyed widespread acceptance in the Unites States.
      METHODS: We performed a cross-sectional study using a GFD questionnaire in 1647
      patients with inflammatory bowel diseases (IBD) participating in the CCFA
      Partners longitudinal Internet-based cohort. RESULTS: A diagnosis of celiac
      disease and non-celiac gluten sensitivity were reported by 10 (0.6%) and 81
      (4.9%) respondents, respectively. Three hundred fourteen (19.1%) participants
      reported having previously tried a GFD and 135 (8.2%) reported current use of
      GFD. Overall 65.6% of all patients, who attempted a GFD, described an improvement
      of their gastrointestinal symptoms and 38.3% reported fewer or less severe IBD
      flares. In patients currently attempting a GFD, excellent adherence was
      associated with significant improvement of fatigue (P < 0.03). CONCLUSIONS: In
      this large group of patients with IBD, a substantial number had attempted a GFD,
      of whom the majority had some form of improvement in gastrointestinal symptoms.
      Testing a GFD in clinical practice in patients with significant intestinal
      symptoms, which are not solely explained by the degree of intestinal
      inflammation, has the potential to be a safe and highly efficient therapeutic
      approach. Further prospective studies into mechanisms of gluten sensitivity in
      IBD are warranted.

PMID- 24865779
TI  - Segmental distribution in refractory ulcerative colitis: a histological
      evaluation in pediatric and adult patients who underwent proctocolectomy.
AB  - BACKGROUND: Histological segmental distribution of ulcerative colitis (UC) may
      represent an early finding of newly diagnosed UC, especially in pediatric
      patients; a sign of Crohn's disease; or a predictor of refractory UC. However,
      its significance remains unknown. This study was performed to compare the final
      pathologic findings in resected total colon and rectum specimens between
      pediatric and adult patients with refractory UC who underwent proctocolectomy and
      clarify the significance of segmental distribution in pediatric patients with UC.
      METHODS: Ninety patients with medically refractory UC (14 with childhood-onset UC
      and 76 with adult-onset UC) who underwent a two-staged operation comprising total
      proctocolectomy and ileal J-pouch anal anastomosis in the first stage were
      included in this study. We retrospectively reviewed all patients' medical records
      and performed a histological evaluation of the resected total colon using Geboes'
      grading system for histological inflammation activity of UC and factors of
      Tanaka's criteria for refractory UC. RESULTS: Histological segmental distribution
      was more frequently observed in the resected colon at surgery in pediatric (64%)
      than in adult patients (21%) with refractory UC. The administration of
      immunomodulators or anti-TNF-alpha antibody within 30 days before surgery was
      more frequently performed in adults than in children. Patients with refractory UC
      with a segmental distribution had a statistically significant relationship with
      shorter duration before surgery (P = 0.0009), male gender (P = 0.0342), and
      higher activity of disease inflammation in rectum (P = 0.0399). Multivariate
      analysis revealed the statistically significant relationship between segmental
      distribution and disease duration before surgery <= 6 years (P = 0.0031).
      CONCLUSIONS: Endoscopists should perform biopsies of both normal and abnormal
      mucosa throughout the total colon and follow changes in the pathological pattern
      because segmental distribution is an important predictor of prognosis.

PMID- 24865780
TI  - Management of cutaneous viral warts.

PMID- 24865782
TI  - Assessment of subjective and hemodynamic tolerance of different high- and low
      flux dialysis membranes in patients undergoing chronic intermittent hemodialysis:
      a randomized controlled trial.
AB  - Clinical experience and experimental data suggest that intradialytic hemodynamic
      profiles could be influenced by the characteristics of the dialysis membranes.
      Even within the worldwide used polysulfone family, intolerance to specific
      membranes was occasionally evoked. The aim of this study was to compare
      hemodynamically some of the commonly used polysulfone dialyzers in Switzerland.
      We performed an open-label, randomized, cross-over trial, including 25
      hemodialysis patients. Four polysulfone dialyzers, A (Revaclear high-flux,
      Gambro, Stockholm, Sweden), B (Helixone high-flux, Fresenius), C (Xevonta high
      flux, BBraun, Melsungen, Germany), and D (Helixone low-flux, Fresenius, Bad
      Homburg vor der Hohe, Germany), were compared. The hemodynamic profile was
      assessed and patients were asked to provide tolerance feedback. The mean score
      (+/-SD) subjectively assigned to dialysis quality on a 1-10 scale was A 8.4 +/-
      1.3, B 8.6 +/- 1.3, C 8.5 +/- 1.6, D 8.5 +/- 1.5. Kt/V was A 1.58 +/- 0.30, B
      1.67 +/- 0.33, C 1.62 +/- 0.32, D 1.45 +/- 0.31. The low- compared with the high
      flux membranes, correlated to higher systolic (128.1 +/- 13.1 vs. 125.6 +/- 12.1
      mmHg, P < 0.01) and diastolic (76.8 +/- 8.7 vs. 75.3 +/- 9.0 mmHg; P < 0.05)
      pressures, higher peripheral resistance (1.44 +/- 0.19 vs. 1.40 +/- 0.18 s *
      mmHg/mL; P < 0.05) and lower cardiac output (3.76 +/- 0.62 vs. 3.82 +/- 0.59
      L/min; P < 0.05). Hypotension events (decrease in systolic blood pressure by >20
      mmHg) were 70 with A, 87 with B, 73 with C, and 75 with D (P < 0.01 B vs. A, 0.05
      B vs. C and 0.07 B vs. D). The low-flux membrane correlated to higher blood
      pressure levels compared with the high-flux ones. The Helixone high-flux membrane
      ensured the best efficiency. Unfortunately, the very same dialyzer correlated to
      a higher incidence of hypotensive episodes. 

PMID- 24865781
TI  - Electrophysiological properties of rat mesenteric lymphatic vessels and their
      regulation by stretch.
AB  - BACKGROUND: In mammals, lymph is propelled centrally primarily via the phasic
      contractions of collecting lymphatic vessels, known as lymphatic pumping.
      Electrophysiological studies conducted in guinea pig and sheep mesenteric
      lymphatic vessels indicate that contractions are initiated in the lymphatic
      muscle by nifedipine-sensitive action potentials (APs). Lymphatic pumping is
      highly sensitive to luminal fluid loading and the mechanical properties of this
      stretch-induced pumping have been consistently studied, in particular in rat
      mesenteric lymphatic vessels. However, membrane potential (Vm) and the
      electrophysiological events underlying stretch-induced lymphatic pumping have not
      been investigated in the rat. The aim of this study was thus to examine the
      properties of rat mesenteric lymphatic muscle Vm under resting conditions and to
      assess changes in Vm caused by distension. METHODS AND RESULTS: Lymphatic muscle
      Vm was measured with sharp intracellular microelectrodes either in unstretched
      conditions or under isometric tension provided by a wire-myograph. In unstretched
      vessels, Vm was -48 +/- 2 mV (n=30). APs (amplitude ~25 mV) were observed at a
      frequency of ~8/min and were abolished by nifedipine. Under isometric tension, Vm
      was less polarized (-36 +/- 1 mV, n=23), even at minimum tension. Increase in
      tension led to increase in contraction strength and contraction/AP frequency,
      while Vm was slightly hyperpolarized and AP amplitude not markedly altered.
      CONCLUSIONS: In our experimental conditions, rat lymphatic muscle has
      electrophysiological characteristics similar to that in other species. It
      responds to an increase in isometric tension with an increase in AP frequency,
      but resting Vm is not significantly affected.

PMID- 24865784
TI  - Factors that determine the length of stay after carotid endarterectomy represent
      opportunities to avoid financial losses.
AB  - BACKGROUND: A postoperative length of stay (LOS) >1 day after elective surgery
      incurs financial losses for hospitals, given fixed diagnosis-related group-based
      reimbursement. We sought to identify factors leading to a prolonged LOS (>1
      postoperative day) after carotid endarterectomy (CEA). METHODS: Patients
      undergoing CEA in 23 centers of the Vascular Study Group of New England between
      2003 and 2011 (n = 8860) were analyzed. Only elective, primary CEAs were
      analyzed, leaving a study cohort of 7108 procedures. Hierarchical multivariable
      logistic regression analysis was performed to identify predictors of a
      postoperative LOS >1 day. A Knaus-Wagner chi-pie analysis was performed to
      determine the relative contributions of each significant covariate to a
      postoperative LOS >1 day. RESULTS: A postoperative LOS >1 day occurred in 17.5%
      of the sample (n = 1244). The average LOS was 1.4 days (range, 1-91 days; median,
      1). There was significant variation in rates of postoperative LOS >1 day across
      centers (range, 5%-100%; P < .001). Factors independently associated with a
      postoperative LOS >1 day and their percentage contribution to the prediction
      model included the need for postoperative intravenous medications for
      hypertension or hypotension (26%), any major adverse event (MAE) postoperatively
      (21%), low-volume (<15 CEAs per year) surgeons (28%), increasing age (7%), female
      gender (4%), positive result on a preoperative stress test (3%), preoperative
      major stroke <=30 days (2%), medication-dependent diabetes (1%), severe chronic
      obstructive pulmonary disease (1%), history of congestive heart failure (1%), and
      CEA performed on Friday (2%). CONCLUSIONS: Certain patient characteristics
      predispose to a postoperative LOS >1 day after elective CEA. However, patient
      characteristics play only a modest (17%) role in determining LOS. The need for
      postoperative blood pressure control and MAEs are the biggest drivers of
      postoperative LOS >1 day, but system factors, such as low operative volume,
      contribute substantially to postoperative LOS >1 day, independent of MAEs. These
      findings can be used to guide quality improvement efforts designed to reduce LOS
      after elective CEA.

PMID- 24865783
TI  - Influence of foot ulceration on cause-specific mortality in patients with
      diabetes mellitus.
AB  - OBJECTIVE: The purpose of this study was to assess the odds of all-cause
      mortality in individuals with diabetic foot ulceration (DFU) compared with those
      with diabetes and no history of DFU. In addition, we sought to determine the
      strength of association of DFU with cardiovascular and nonvascular mortality.
      METHODS: We obtained data for a cohort of patients who attended a secondary care
      diabetic foot clinic or a general diabetes clinic between 2009 and 2010. A clinic
      cohort of patients with diabetes and no history of DFU provided a control group.
      Cause-specific mortality was recorded during a median follow-up duration of 3.6
      years (interquartile range, 3.3-4.2 years). The association between DFU and all
      cause mortality was evaluated by Cox regression. The association between DFU and
      cardiovascular mortality was determined by competing risk modeling. RESULTS: We
      recorded 145 events of all-cause mortality and 27 events of cardiovascular
      mortality among 869 patients with diabetes. After adjustment for potential
      confounders, DFU was associated with both cardiovascular disease (hazard ratio,
      2.53; 95% confidence interval, 0.98-6.49; P = .05) and all-cause mortality
      (hazard ratio, 3.98; 95% confidence interval, 2.55-6.21; P < .001). The
      proportion of deaths attributable to cardiovascular disease was similar between
      the groups (18% with diabetes only and 19% with DFU; P = .91). CONCLUSIONS: DFU
      is associated with premature death from vascular and nonvascular causes.

PMID- 24865785
TI  - Late aneurysm rupture after delayed secondary open conversion with partial
      explantation for failed endovascular repair.
AB  - A delayed secondary open conversion (SOC) after endovascular aneurysm repair may
      be necessary due to a failing graft. Many surgical techniques can be performed,
      and one such approach is partial explantation of the graft with resuturing of a
      new graft to the retained components of the endograft. No guidelines exist with
      regards to the follow-up of retained endovascular components after a delayed SOC.
      The theoretical risk of endoleaks remains with retained components, and this case
      demonstrates the development of a type Ib endoleak after SOC leading to free flow
      of blood into a partially resected aneurysm sac and causing a symptomatic
      aneurysm rupture. 

PMID- 24865786
TI  - Shuttering of the superior mesenteric artery during fenestrated endovascular
      aneurysm repair.
AB  - OBJECTIVE: Shuttering occurs when a scallop or fenestration does not align
      perfectly with the target vessel ostium and is potentially minimized by stenting.
      The current United States Food and Drug Administration-approved fenestrated
      endovascular aneurysm repair (f-EVAR) device is most commonly configured with an
      unstented superior mesenteric artery (SMA) scallop, thereby subjecting the SMA to
      risk of partial coverage. We aimed to describe the incidence, severity, and
      clinical effect of SMA shuttering during f-EVAR. METHODS: Patients undergoing f
      EVAR using the commercially available Zenith (Cook Medical, Bloomington, Ind)
      fenestrated stent graft system containing an SMA scallop at our institution
      between September 2012 and January 2014 were included for analysis. Corrected
      multiplanar reformatted images on postoperative computed tomographic angiography
      were reviewed to measure SMA shuttering, defined as the percentage of scallop
      misalignment relative to the SMA ostial diameter. RESULTS: Of the 28 f-EVAR cases
      performed at our institution during the study period, 18 patients (78% male) had
      an SMA scallop and were included in this analysis. The median age was 78 years
      (interquartile range [IQR], 72-81 years), and the median abdominal aortic
      aneurysm size was 61 mm (IQR, 56-64 mm). Fifty-one vessels were targeted (18 SMA
      scallops, 32 renal fenestrations, 1 renal snorkel), with covered stents placed in
      all fenestrations. Target vessel catheterization and successful branch stent
      deployment was achieved in 100% of patients. SMA shuttering measured on
      postoperative computed tomographic angiography of any amount occurred in 50% of
      patients (range of SMA shuttering, 12%-40%). The severity of SMA shuttering
      varied: one patient had 11% to 20%, four had 21% to 30%, and four had 31 to 40%.
      When compared with patients without shuttering, patients with any SMA shuttering
      were noted to have a shorter infra-SMA neck length (17 vs. 25 mm; P = .007),
      higher volume of intraprocedural contrast administration (100 vs. 66 mL; P =
      .001), and had a trend toward longer procedural durations (240 vs. 188 minutes; P
      = .09). No association was found between SMA shuttering and the preoperative
      measured clock position of the visceral vessels, percentage of device oversizing,
      number of target vessels per patient, aortic diameter at the SMA or seal zone,
      aneurysm neck morphology, infrarenal neck length, scallop width, or SMA ostial
      diameter. No acute or chronic events of mesenteric ischemia were noted during a
      median clinical follow-up period of 11 months (IQR, 5-14 months). CONCLUSIONS:
      Even with the custom design of currently available fenestrated technology,
      shuttering of the SMA occurred in one-half of the patients in our cohort,
      although no clinical events were noted. Further details of the incidence,
      magnitude, and tolerance of SMA shuttering during f-EVAR are warranted to fully
      understand the clinical implication of this radiographic finding. Future design
      considerations for advanced EVAR should take into account SMA shuttering to
      further refine operative planning.

PMID- 24865791
TI  - Parasitic infections on the shore of Lake Victoria (East Africa) detected by Mini
      FLOTAC and standard techniques.
AB  - BACKGROUND: Helminths and protozoa infections pose a great burden especially in
      developing countries, due to morbidity caused by both acute and chronic
      infection. The aim of our survey was to analyze the intestinal parasitic burden
      in communities from Mwanza region, Tanzania. METHODS: Subjects (n=251) from four
      villages on the South of Lake Victoria have been analyzed for intestinal
      parasites with direct smear (DS), formol-ether concentration method (FECM) and
      the newly developed Mini-FLOTAC technique; urinary schistosomiasis was also
      assessed in a subsample (n=151); symptoms were registered and correlation between
      clinic and infections was calculated by chi-squared test and logistical
      regression. RESULTS: Out of the subjects screened for intestinal and for urinary
      parasites, 87% (218/251) were found positive for any infection, 69% (174/251)
      carried a helminthic and 67% (167/251) a protozoan infection, almost half of them
      had a double or triple infection. The most common helminths were hookworms,
      followed by Schistosoma mansoni and Schistosoma haematobium. Among protozoa, the
      most common was Entamoeba coli followed by Entamoeba histolytica/dispar and
      Giardia intestinalis. Mini-FLOTAC detected a number of helminth infections
      (61.7%) higher than FECM (38.6%) and DS (17.9%). Some positive associations with
      abdominal symptoms were found and previous treatment was negatively correlated
      with infection. CONCLUSION: Despite the limited size of the examined population
      the current study indicates a high prevalence of intestinal parasitic infection
      in Bukumbi area, Tanzania, and Mini-FLOTAC showed to be a promising diagnostic
      tool for helminth infections. This high parasitic burden calls for starting a
      regular deworming programme and other preventive interventions in schools and in
      the community.

PMID- 24865792
TI  - Risk assessment of flavivirus transmission in Namibia.
AB  - The role of arboviruses causing acute febrile illness in sub-Saharan Africa is
      receiving more attention. Reports of dengue in tourists were published nearly 10
      years ago in Namibia, but the current epidemiology of arboviruses is unknown and
      surveys of mosquito vectors have not been carried out since the 1950s. To begin
      addressing this knowledge gap, a prospective cross-sectional study was conducted
      using samples from volunteer blood donors linked to questionnaire. Serum samples
      were tested using a Dengue IgG Indirect ELISA which measured exposure to dengue
      virus/flaviviruses. Entomological samples were collected from tires during the
      rainy season (February-March 2012) in six locations across Namibia's capital
      city, Windhoek. Among 312 blood donors tested, 25 (8.0%) were positive for dengue
      virus/flavivirus exposure. The only significant risk factor was age group with
      high exposure rates among those older than 50 (29%) compared with those below 40
      years old (between 2.9% and 8.3%) (P<0.002). Larvae and pupae of Aedes aegypti
      and Culex pipiens complex accounted for 100% of the 2751 samples collected, of
      which only 12.2% (n=336) were Ae. aegypti. Each site demonstrated high
      variability of species composition between sampling times. While the significant
      dengue virus/flavivirus exposure rate among those above 50 years old is likely
      indicative of the West Nile epidemic in the 70s and 80s, the low exposure among
      those under 50 suggests that flaviviruses are still circulating in Namibia. While
      Ae. aegypti and C. pipiens sp. may play a role in future epidemics, the
      significance of presence may be reduced due to short rain periods, dry, arid,
      cold winters and policies and social understandings that limit non-structured
      storage and use of tires in low income areas. Future studies should further
      characterize the circulating arboviruses and investigate mosquito ecology
      nationally to map areas at higher risk for future arbovirus outbreaks. 

PMID- 24865793
TI  - Antiprotozoal activity and DNA binding of N-substituted N-phenylbenzamide and 1,3
      diphenylurea bisguanidines.
AB  - Two series of N-alkyl, N-alkoxy, and N-hydroxy bisguanidines derived from the N
      phenylbenzamide and 1,3-diphenylurea scaffolds were synthesised in three steps
      from the corresponding 4-amino-N-(4-aminophenyl)benzamide and 1,3-bis(4
      aminophenyl)urea, respectively. All of the new compounds were evaluated in vitro
      against T. b. rhodesiense (STIB900) trypomastigotes and Plasmodium falciparum
      NF54 parasites (erythrocytic stage). N-alkoxy and N-hydroxy derivatives showed
      weak micromolar range IC50 values against T. b. rhodesiense and P. falciparum
      whereas the N-alkyl analogues displayed submicromolar and low nanomolar IC50
      values against P. falciparum and Trypanosoma brucei, respectively. Two compounds,
      4-(2-ethylguanidino)-N-(4-(2-ethylguanidino)phenyl)benzamide dihydrochloride (7b)
      and 4-(2-isopropylguanidino)-N-(4-(2-isopropylguanidino)phenyl)benzamide
      dihydrochloride (7c), which showed favourable drug-like properties and in vivo
      efficacy (100% cures) in the STIB900 mouse model of acute human African
      trypanosomiasis represent interesting leads for further in vivo studies. The
      binding of these compounds to AT-rich DNA was confirmed by surface plasmon
      resonance (SPR) biosensor experiments. 

PMID- 24865796
TI  - BRDT gene sequence in human testicular pathologies and the implication of its
      single nucleotide polymorphism (rs3088232) on fertility.
AB  - Bromodomain testis-specific (BRDT) protein is essential for the normal process of
      spermatogenesis. Mutant mice that expressed truncated BRDT had impaired
      testicular histology with severely reduced sperm concentration and abnormal sperm
      morphology, while a model of knockout Brdt mice with no BRDT protein had complete
      meiotic arrest. A BRDT single nucleotide polymorphism (SNP) (rs3088232) was
      reported as being associated with infertility in men. We assessed testicular
      specimens of 276 azoospermic men who underwent testicular sperm extraction to
      search for specimens that showed spermatogenic impairments similar to those of
      mutant BRDT mice. Ten similar specimens were selected for BRDT gene sequencing
      and they revealed three NCBI-reported SNPs (rs10783071, rs3088232 and rs10747493)
      variously distributed among them. Bioinformatics analysis predicted that they
      would not affect protein activity. Further assessment of rs3088232 frequency in a
      large group of non-obstructive azoospermia men and fertile controls demonstrated
      no significant difference between them (27.2 and 21.7% respectively; p = 0.122,
      Fisher's exact test). We conclude that the testicular impairments observed in the
      10 specimens were not a consequence of BRDT gene mutation. The association
      between BRDT rs3088232 and infertility that had been reported in other studies
      was not supported.

PMID- 24865797
TI  - SOD2 gene polymorphism and muscle damage markers in elite athletes.
AB  - Exercise-induced oxidative stress is a state that primarily occurs in athletes
      involved in high-intensity sports when pro-oxidants overwhelm the antioxidant
      defense system to oxidize proteins, lipids, and nucleic acids. During exercise,
      oxidative stress is linked to muscle metabolism and muscle damage, because
      exercise increases free radical production. The T allele of the Ala16Val (rs4880
      C/T) polymorphism in the mitochondrial superoxide dismutase 2 (SOD2) gene has
      been reported to reduce SOD2 efficiency against oxidative stress. In the present
      study we tested the hypothesis that the SOD2 TT genotype would be
      underrepresented in elite athletes involved in high-intensity sports and
      associated with increased values of muscle and liver damage biomarkers. The study
      involved 2664 Caucasian (2262 Russian and 402 Polish) athletes. SOD2 genotype and
      allele frequencies were compared to 917 controls. Muscle and liver damage markers
      [creatine kinase (CK), creatinine, alanine transaminase (ALT), aspartate
      transaminase (AST), alkaline phosphatase (ALP)] were examined in serum from 1444
      Russian athletes. The frequency of the SOD2 TT genotype (18.6%) was significantly
      lower in power/strength athletes (n = 524) compared to controls (25.0%, p =
      0.0076) or athletes involved in low-intensity sports (n = 180; 33.9%, p <
      0.0001). Furthermore, the SOD2 T allele was significantly associated with
      increased activity of CK (females: p = 0.0144) and creatinine level (females: p =
      0.0276; males: p = 0.0135) in athletes. Our data show that the SOD2 TT genotype
      might be unfavorable for high-intensity athletic events.

PMID- 24865798
TI  - Serelaxin : a potential new drug for the treatment of acute heart failure.
AB  - INTRODUCTION: The incidence and mortality related to acute heart failure (AHF)
      have increased in the recent decades despite clinical trials of multiple agents
      and considerable progress in cardiovascular disease overall. AREAS COVERED: This
      article reviews serelaxin , a new investigational drug in the treatment of AHF.
      It provides the background of the available treatments and focuses on serelaxin
      mechanisms, pharmacology, clinical features and its potential role in AHF. EXPERT
      OPINION: Recent clinical trials of serelaxin (Pre-RELAX-AHF; RELAX-AHF) have
      provided a new hope in AHF. They have demonstrated significant serelaxin-related
      improvement in heart failure symptoms, length of hospital stay as well as
      mortality reduction in AHF patients. These findings were in the context of early
      administration in the course of AHF presentation in patients with normal or high
      blood pressures, thus highlighting the drug's strengths based on its molecular
      mechanisms of action. Overall, serelaxin is a promising therapy, and further
      studies aimed at reproducibility of prior results, safety and hemodynamic effects
      of serelaxin, as well as investigation of the molecular reasons for such effects
      are currently under way.

PMID- 24865795
TI  - Nurse practitioners can effectively deliver pain coping skills training to
      osteoarthritis patients with chronic pain: A randomized, controlled trial.
AB  - A multisite, randomized, controlled clinical effectiveness trial was conducted
      for osteoarthritis patients with chronic pain of the knee or hip. Adult health
      nurse practitioners provided a 10-session intervention, pain coping skills
      training (PCST), in patients' doctors' offices (N=129 patients); the control
      group received usual care (N=127 patients). Primary outcomes assessed at
      baseline, posttreatment, 6-month follow-up, and 12-month follow-up were: pain
      intensity, physical functioning, psychological distress, self-efficacy,
      catastrophizing, use of coping strategies, and quality of life. Secondary
      measures included fatigue, social functioning, health satisfaction, and use of
      pain medication. Methods favoring external validity, consistent with pragmatic,
      effectiveness research, were utilized. Primary ITT and secondary per-protocol
      analyses were conducted. Attrition was within the expected range: 11% at
      posttreatment and 29% at 12-month follow-up; rates did not differ between groups.
      Omnibus ITT analyses across all assessment points indicated significant
      improvement for the PCST group compared with the control group for pain
      intensity, physical functioning, psychological distress, use of pain coping
      strategies, and self-efficacy, as well as fatigue, satisfaction with health, and
      reduced use of pain medication. Treatment effects were robust to covariates
      (demographics and clinical sites). Trends in the outcomes across the assessments
      were examined. All outcomes, except for self-efficacy, were maintained through
      the 12-month follow-up; effects for self-efficacy degraded over time. Per
      protocol analyses did not yield greater effect sizes. Comparisons of PCST
      patients who were more vs less treatment adherent suggested greater effectiveness
      for patients with high adherence. Results support the effectiveness of nurse
      practitioner delivery of PCST for chronic osteoarthritis pain. 

PMID- 24865794
TI  - Research designs for proof-of-concept chronic pain clinical trials: IMMPACT
      recommendations.
AB  - Proof-of-concept (POC) clinical trials play an important role in developing novel
      treatments and determining whether existing treatments may be efficacious in
      broader populations of patients. The goal of most POC trials is to determine
      whether a treatment is likely to be efficacious for a given indication and thus
      whether it is worth investing the financial resources and participant exposure
      necessary for a confirmatory trial of that intervention. A challenge in designing
      POC trials is obtaining sufficient information to make this important go/no-go
      decision in a cost-effective manner. An IMMPACT consensus meeting was convened to
      discuss design considerations for POC trials in analgesia, with a focus on
      maximizing power with limited resources and participants. We present general
      design aspects to consider including patient population, active comparators and
      placebos, study power, pharmacokinetic-pharmacodynamic relationships, and
      minimization of missing data. Efficiency of single-dose studies for treatments
      with rapid onset is discussed. The trade-off between parallel-group and crossover
      designs with respect to overall sample sizes, trial duration, and applicability
      is summarized. The advantages and disadvantages of more recent trial designs,
      including N-of-1 designs, enriched designs, adaptive designs, and sequential
      parallel comparison designs, are summarized, and recommendations for
      consideration are provided. More attention to identifying efficient yet powerful
      designs for POC clinical trials of chronic pain treatments may increase the
      percentage of truly efficacious pain treatments that are advanced to confirmatory
      trials while decreasing the percentage of ineffective treatments that continue to
      be evaluated rather than abandoned. 

PMID- 24865799
TI  - Molecular and phylogenetic characterization based on the complete genome of a
      virulent pathotype of Newcastle disease virus isolated in the 1970s in Brazil.
AB  - Newcastle disease (ND) is caused by the avian paramyxovirus type 1 (APMV-1) or
      Newcastle disease virus (NDV) that comprises a diverse group of viruses with a
      single-stranded, negative-sense RNA genome. ND is one of the most important
      diseases of chickens, because it severely affects poultry production worldwide.
      In the 1970s, outbreaks of virulent ND were recorded in Brazil, and the strain
      APMV-1/Chicken/Brazil/SJM/75 (SJM) of NDV was isolated. This strain was
      characterized as highly pathogenic for chickens but not pathogenic for other bird
      species. Here we present the complete genome of NDV strain SJM and investigate
      the phylogenetic relationships of this virus with other NDV strains in terms of
      genome and proteins composition, as well as characterizing its evolution process.
      The NDV strain SJM is categorized as a velogenic virus and the complete genome is
      15,192 nucleotides in length, consisting of six genes in the order 3'-NP-P-M-F-HN
      L-5'. The presence of the major pathogenic determinant of NDV strains ((112)R-R-Q
      K-R?F(117)) was identified in the Fusion protein of the NDV strain SJM. In
      addition, phylogenetic analysis classified the NDV strain SJM as a member of
      class II, genotype V, and indicates that this virus help us in the understanding
      of the evolutionary process of strains belonging to this genotype. This study
      contributes to the growing interest involving the characterization of NDV
      isolates to improve our current understanding about the epidemiology,
      surveillance and evolution of the pathogenic strains. 

PMID- 24865800
TI  - Trauma exposure and posttraumatic stress disorder among incarcerated men.
AB  - Trauma exposure and trauma-related symptoms are prevalent among incarcerated men,
      suggesting a need for behavioral health intervention. A random sample of adult
      males (N = 592) residing in a single high-security prison were screened for
      trauma exposure and posttraumatic stress disorder (PTSD) symptoms. Trauma was a
      universal experience among incarcerated men. Rates of current PTSD symptoms and
      lifetime PTSD were significantly higher (30 to 60 %) than rates found in the
      general male populations (3 to 6 %). Lifetime rates of trauma and PTSD were
      associated with psychiatric disorders. This study suggests the need for a gender
      sensitive response to trauma among incarcerated men with modification for
      comorbid mental disorders and type of trauma exposure. Developing gender
      sensitive trauma interventions for incarcerated men and testing them is necessary
      to improve the behavioral health outcomes of incarcerated men who
      disproportionately return to urban communities. 

PMID- 24865802
TI  - Sinister syncope.

PMID- 24865801
TI  - Utilization of mental health services by minority urban adults: psychosocial
      predictors.
AB  - Although most mental disorders have their first onset by young adulthood, there
      are few longitudinal studies of these problems and related help-seeking behavior.
      The present study examined some early and current predictors of the use of mental
      health services among African-American and Puerto Rican participants in their mid
      30s. The 674 participants (52.8 % African Americans, 47.2 % Puerto Ricans; 60.1 %
      women) in this study were first seen in 1990 when the participants attended
      schools serving the East Harlem area of New York City. A structural equation
      model controlling for the participants' gender, educational level in emerging
      adulthood, and age at the most recent data collection showed significant
      standardized pathways from both ethnicity (beta = -0.28; z = -4.82; p < 0.001)
      and psychological symptoms (beta = 0.15; z = 2.41; p < 0.05), both measured in
      emerging adulthood, to smoking in the early 30s. That, in turn, was associated
      with certain physical diseases and symptoms (i.e., respiratory) in the mid-30s
      (beta = 0.16; z = 2.59; p < 0.05). These physical diseases and symptoms had a
      cross-sectional association with family financial difficulty in the mid-30s (beta
      = 0.21; z = 4.53; p < 0.001), which in turn also had a cross-sectional
      association with psychiatric disorders (beta = 0.30; z = 5.30; p < 0.001).
      Psychiatric disorders had a cross-sectional association with mental health
      services utilization (beta = 0.65; z = 13.25; p < 0.001). Additional pathways
      from the other domains to mental health services utilization in the mid-30s were
      also supported by the mediating role of psychiatric disorders. Results obtained
      from this research offer theoretical and practical information regarding the
      processes leading to the use of mental health services. 

PMID- 24865803
TI  - Investigational screening for Babesia microti in a large repository of blood
      donor samples from nonendemic and endemic areas of the United States.
AB  - BACKGROUND: Babesia microti, a transfusion-transmissible intraerythrocytic
      parasite, is increasing in frequency in the United States with no available FDA
      licensed donor screening assay. We utilized investigational arrayed fluorescence
      immunoassay (AFIA) and polymerase chain reaction (PCR) to detect B. microti
      antibodies and DNA in blood donors. STUDY DESIGN AND METHODS: AFIA and real-time
      PCR were performed on frozen paired EDTA plasma (AFIA) and EDTA whole blood (PCR)
      samples collected from May to September 2010 to 2011 in nonendemic (Arizona [AZ]
      and Oklahoma [OK]), moderately endemic (Minnesota [MN] and Wisconsin [WI]), and
      highly endemic (Connecticut [CT] and Massachusetts [MA]) areas of the United
      States. AFIA utilized B. microti piroplasm as an antigen substrate; PCR primers
      and probes targeted the B. microti 18S ribosomal RNA gene. Data from AZ and OK
      were used to calculate specificity. All AFIA- or PCR-positive or -inconclusive
      donors were deferred, notified, and invited to participate in a follow-up study
      involving repeat testing and a demographic and risk-factor questionnaire.
      Recipient tracing was performed for any cellular component transfused at index,
      at subsequent donation, or within the prior 12 months. RESULTS: Testing of 13,269
      paired samples included 4022 from AZ and OK, 4167 from MN and WI, and 5080 from
      CT and MA. B. microti antibody and/or DNA prevalences were 0.025% (95% confidence
      interval [CI], 0.00%-0.14%), 0.12% (95% CI, 0.04%-0.28%), and 0.75% (95% CI,
      0.53%-1.03%) in the nonendemic, mid-endemic, and high-endemic regions,
      respectively. Specificities were 99.95% (95% CI, 99.82%-99.99%) at a 1-in-64 AFIA
      cutoff and 99.98% (95% CI, 99.86%-100.00%) at a 1-in-128 cutoff. CONCLUSIONS: B.
      microti prevalence followed expected geographical patterns. Screening was
      feasible with a performance comparable or superior to other infectious disease
      blood donor screening assays.

PMID- 24865804
TI  - Understanding the dosimetric powder EPR spectrum of sucrose by identification of
      the stable radiation-induced radicals.
AB  - Sucrose, the main component of table sugar, present in nearly every household and
      quite radiation sensitive, is considered as an interesting emergency dosemeter.
      Another application of radiation-induced radicals in sugars is the detection of
      irradiation in sugar-containing foodstuffs. The complexity of electron
      paramagnetic resonance (EPR) spectra of radicals in these materials, as a result
      of many hyperfine interactions and the multi-compositeness of the spectra of
      individual sugars, complicate dose assessment and the improvement of protocols
      for control and identification of irradiated sugar-containing foodstuffs using
      EPR. A thorough understanding of the EPR spectrum of individual irradiated sugars
      is desirable when one wants to reliably use them in a wide variety of dosimetric
      applications. Recently, the dominant room temperature stable radicals in
      irradiated sucrose have been thoroughly characterised using EPR, electron nuclear
      double resonance (ENDOR) and ENDOR-induced EPR. These radicals were structurally
      identified by comparing their proton hyperfine and g-tensors with the results of
      Density Functional Theory calculations for test radical structures. In this
      paper, the authors use the spin Hamiltonian parameters determined in these
      studies to simulate powder EPR spectra at the standard X-band (9.5 GHz), commonly
      used in applications, and at higher frequencies, up to J-band (285 GHz),
      rendering spectra with higher resolution. A few pitfalls in the simulation
      process are highlighted. The results indicate that the major part of the
      dosimetric spectrum can be understood in terms of three dominant radicals, but as
      yet unidentified radicals also contribute in a non-negligible way. 

PMID- 24865805
TI  - The effect of rapid maxillary expansion on pharyngeal airway pressure during
      inspiration evaluated using computational fluid dynamics.
AB  - INTRODUCTION: Recent evidence suggests that rapid maxillary expansion (RME) is an
      effective treatment of obstructive sleep apnea syndrome (OSAS) in children with
      maxillary constriction. Nonetheless, the effect of RME on pharyngeal airway
      pressure during inspiration is not clear. The purpose of this retrospective study
      was to evaluate changes induced by the RME in ventilation conditions using
      computational fluid dynamics. METHODS: Twenty-five subjects (14 boys, 11 girls;
      mean age 9.7 years) who required RME had cone-beam computed tomography (CBCT)
      images taken before and after the RME. The CBCT data were used to reconstruct 3
      dimensional shapes of nasal and pharyngeal airways. Measurement of airflow
      pressure was simulated using computational fluid dynamics for calculating nasal
      resistance during exhalation. This value was used to assess maximal negative
      pressure in the pharyngeal airway during inspiration. RESULTS: Nasal resistance
      after RME, 0.137 Pa/(cm(3)/s), was significantly lower than that before RME,
      0.496 Pa/(cm(3)/s), and the maximal negative pressure in the pharyngeal airway
      during inspiration was smaller after RME (-48.66 Pa) than before (-124.96 Pa).
      CONCLUSION: Pharyngeal airway pressure during inspiration is decreased with the
      reduction of nasal resistance by the RME. This mechanism may contribute to the
      alleviation of OSAS in children.

PMID- 24865806
TI  - Surgery for reflux induced airway disease: a systematic review.
AB  - OBJECTIVES: 1. Evaluate the current evidence regarding the efficacy and safety of
      anti-reflux surgery for the treatment of severe gastroesophageal reflux-related
      airway disease in children. 2. Provide evidence based recommendations regarding
      indications and outcomes of anti-reflux surgery for airway disease in children.
      METHODS: An a priori protocol was defined to identify all articles addressing
      anti-reflux surgery for the treatment of reflux-related airway disease in
      children where details regarding the diagnosis, treatment, and outcomes were
      clearly presented. The search was inclusive of all references available through
      August 30, 2013 and included electronic databases to identify candidate articles
      as well as a comprehensive series of crosschecks. The two authors independently
      determined which references met inclusion criteria, extracted data, and assigned
      levels of evidence. Data were pooled using a random effects model due to
      significant study heterogeneity. RESULTS: Fourteen articles met inclusion
      criteria. The overall level of evidence was grade C. There was significant
      heterogeneity among the studies (I(2)=82.7%; p<0.001). However, each article
      uniformly presented cases suggesting that anti-reflux surgery is efficacious and
      safe in treating children with severe reflux-related respiratory disease. The
      pooled success rate for complete or partial resolution of symptoms after anti
      reflux surgery was 0.91 (95% CI: 0.88, 0.94). The pooled success rate for
      complete symptom resolution after surgery was 0.72 (95% CI: 0.62, 0.83).
      CONCLUSION: The current literature suggests that anti-reflux surgery is an
      effective and safe treatment for severe reflux-related airway disease. However,
      the level of evidence lacks strength and further investigation is warranted.

PMID- 24865807
TI  - Chronic tympanic membrane perforation in an animal model.
AB  - OBJECTIVE: The aim of this study was to revalidate and reproduce a chronic
      tympanic membrane perforation animal model. STUDY DESIGN: Prospective, animal
      study. METHODS: Eight female chinchillas underwent bilateral thermal myringotomy.
      The edges of the perforation were folded inward using microflaps. The
      perforations were followed over time to monitor the course of closure. RESULTS:
      Two animals were excluded from the study because of ear infection. None of the
      other tympanic membrane perforations remained open. The closing time varied from
      4 to 6 weeks. CONCLUSIONS: Our findings demonstrate that the thermal myringotomy
      combined with infolding technique is not a reliable and consistent method to
      create a chronic tympanic membrane perforation. The closing time is shorter than
      expected and varies among the study subjects. There is a clear need for
      developing a reliable chronic tympanic membrane perforation model.

PMID- 24865808
TI  - Iatrogenic velopharyngeal insufficiency caused by neonatal nasogastric feeding
      tube.
AB  - Complications from a prolonged nasogastric tube intubation, though seldom
      reported, are well described. Herein we describe the first two reported cases of
      velopharyngeal insufficiency secondary to velopharyngeal scarring and immobility
      from repetitive nasogastric tube insertions and prolonged use. Differing only in
      location, the proposed pathophysiologic mechanism of injury is identical to that
      of the nasogastric tube syndrome, a rare and serious, well described entity
      consisting of bilateral vocal fold paralysis due to pressure-induced ulceration
      of the posterior cricoarytenoid musculature. 

PMID- 24865809
TI  - Pilot study: Association between Helicobacter pylori in adenoid hyperplasia and
      reflux episodes detected by multiple intraluminal impedance in children.
AB  - OBJECTIVES: The aim of this pilot study was to investigate an association between
      laryngopharyngeal reflux detected by combined multiple intraluminal impedance and
      pH monitoring and Helicobacter pylori in adenoid hyperplasia detected with real
      time polymerase chain reaction (PCR). METHODS: The study group consisted of 30
      children (median age 5.34 years) with extraesophageal symptoms of
      gastroesophageal reflux disease with adenoid hyperplasia. All children underwent
      adenoidectomy with subsequent PCR detection of H. pylori DNA in the tissue and
      multiple intraluminal impedance and pH monitoring. The most proximal impedance
      sensor was located 1cm caudal to the entrance of the oesophagus. RESULTS: We
      found significant differences in the number of reflux episodes among patients
      with PCR positivity (median 35) and negativity (median 0) of H. pylori (p-value
      of Mann-Whitney U-test 0.0056). Patients with PCR positivity of H. pylori had
      significantly more reflux episodes reaching the upper oesophageal sphincter (p
      value of Mann-Whitney U-test 0.023). The absence of reflux episode was the only
      independent factor for PCR negativity of H. pylori in the multiple logistic
      regression model. CONCLUSIONS: These results support the hypothesis that reflux
      episodes reaching the upper oesophageal sphincter may play an important role in
      the transmission of H. pylori into lymphoid tissue of the nasopharynx and thus
      may contribute to adenoid hyperplasia in children.

PMID- 24865811
TI  - Through the looking glass: witnessing host-virus interplay in zebrafish.
AB  - Host-pathogen interactions can be very complex at all scales; understanding organ
      or organism-level events require in vivo approaches. Besides traditional host
      models such as mice, the zebrafish offers an attractive cocktail of optical
      accessibility and genetic tractability, blended with a vertebrate-type immunity,
      where innate responses can easily be separated from adaptive ones. Applied to
      viral infections, this model has revealed unexpected idiosyncrasies among organs,
      which we believe may apply to the human situation. We also argue that the dynamic
      analysis of virus spread and immune response in zebrafish make this model
      particularly well suited to the exploration of the concept of infection tolerance
      and resistance in relation to viral diseases. 

PMID- 24865812
TI  - Motor unit number index (MUNIX) in the orbicularis oculi muscle of healthy
      subjects.
AB  - INTRODUCTION: The motor unit number index (MUNIX) refers to an
      electrophysiological method that measures the number of motor units in the
      surface electromyographic interference pattern (SIP) recorded during graded
      muscle contractions. MUNIX studies of limb muscles have been conducted, but MUNIX
      studies of bulbo-facial muscles have not been reported. METHODS: We assessed
      bilateral orbicularis oculi muscles using MUNIX, and the reference values and
      reproducibility of MUNIX and motor unit size index (MUSIX) were investigated in
      healthy subjects. RESULTS: In this study, MUNIX was applied successfully to the
      orbicularis oculi muscles and showed good reproducibility. The correlation
      coefficients for MUNIX and MUSIX were 0.803 and 0.592, respectively, and the
      coefficients of variation were 20.9% and 8.5%, respectively. CONCLUSIONS: The
      MUNIX procedure for the orbicularis oculi muscle would be a useful tool for
      evaluating bulbar symptoms, especially in amyotrophic lateral sclerosis.

PMID- 24865810
TI  - Structure of the atypical bacteriocin pectocin M2 implies a novel mechanism of
      protein uptake.
AB  - The colicin-like bacteriocins are potent protein antibiotics that have evolved to
      efficiently cross the outer membrane of Gram-negative bacteria by parasitizing
      nutrient uptake systems. We have structurally characterized the colicin M-like
      bacteriocin, pectocin M2, which is active against strains of Pectobacterium spp.
      This unusual bacteriocin lacks the intrinsically unstructured translocation
      domain that usually mediates translocation of these bacteriocins across the outer
      membrane, containing only a single globular ferredoxin domain connected to its
      cytotoxic domain by a flexible alpha-helix, which allows it to adopt two distinct
      conformations in solution. The ferredoxin domain of pectocin M2 is homologous to
      plant ferredoxins and allows pectocin M2 to parasitize a system utilized by
      Pectobacterium to obtain iron during infection of plants. Furthermore, we
      identify a novel ferredoxin-containing bacteriocin pectocin P, which possesses a
      cytotoxic domain homologous to lysozyme, illustrating that the ferredoxin domain
      acts as a generic delivery module for cytotoxic domains in Pectobacterium. 

PMID- 24865813
TI  - Associations between early alcohol and tobacco use and prolonged time to puberty
      in boys.
AB  - BACKGROUND: Previous research has demonstrated a relationship between prepubertal
      alcohol and tobacco use and delayed pubertal characteristics in girls. Although,
      laboratory research indicates that alcohol and tobacco use inhibits sexual
      maturation in male rats, human research in this area is lacking. To address this
      question among boys, we conducted a study to explore the association between
      early use of alcohol and tobacco and time to development of secondary sexual
      characteristics. METHODS: The study population included 3199 boys interviewed
      between the ages of 11 and 21. Participants reported the ages at which they first
      experienced body hair growth, deepening of the voice and facial hair growth.
      Early alcohol and tobacco use were defined as first use preceding the age of
      pubertal development among those reporting regular consumption patterns. Hazard
      ratios (HR) and 95% confidence intervals (CI) were calculated using Cox
      proportional hazard models. RESULTS: Early alcohol use was associated with longer
      time to body hair growth (HR 0.77; 95% CI 0.69-0.87), voice changes (HR 0.72; 95%
      CI 0.64-0.82) and facial hair growth (HR 0.77; 95% CI 0.68-0.86), after adjusting
      for tobacco use and age at interview. Tobacco use was not independently
      associated with the puberty indicators after controlling for alcohol use and age
      at interview. CONCLUSIONS: Our findings are consistent with the hypothesis that
      alcohol may inhibit puberty onset in boys, an association that has been
      previously observed among young girls. Thus, alcohol may be an exposure deserving
      more scrutiny as a disruptor to normal pubertal development.

PMID- 24865814
TI  - Treatment progress in medium security hospital settings for women: changes in
      symptoms, personality and service need from admission to discharge.
AB  - BACKGROUND: Service evaluations of medium secure hospital facilities for women
      are underrepresented in the extant literature. HYPOTHESIS: That positive changes
      in symptoms, personality traits and service need would be evident between
      admission and discharge among women in a medium security hospital service.
      METHODS: A pre-test/post-test design was used, with comparisons made between
      admission and pre-discharge points on a variety of measures of psychiatric
      symptoms and personality traits. RESULTS: There were significant improvements in
      mood according to Beck Depression Inventory scores, mood and other symptoms of
      mental disorder and distress as measured by the Brief Psychiatric Rating Scale
      and the Modified Post Traumatic Stress Disorder Symptom Scale, personality traits
      recorded using the Millon Clinical Multiaxial Inventory III and service need as
      measured by the Camberwell Assessment of Need, Forensic Version.
      CONCLUSIONS/IMPLICATIONS FOR PRACTICE: Significant positive change during
      treatment, in all clinical areas, is encouraging given poor outcomes for women
      reported in other research. Findings cannot, however, be unequivocally attributed
      to the treatments given. Further work is needed to improve early engagement and
      tailor treatment more specifically to the needs of a heterogeneous population.

PMID- 24865816
TI  - Decreased Vbeta8.2 T-cells in neonatal rats exposed prenatally to Staphylococcal
      enterotoxin B are further deleted by restimulation in an in vitro cultured
      thymus.
AB  - Staphylococcal enterotoxin B (SEB) administration during adulthood can cause the
      anergy or deletion of variable portion of the ? chain (V?)?expressing T cells.
      However, the effect of maternal SEB administration during pregnancy on the
      thymocytes of neonatal rats remains to be elucidated. In the present study,
      pregnant rats at gestational day 16 were intravenously injected with 15 ug SEB.
      The present study revealed that prenatal exposure of SEB significantly increased
      the proportion of cluster of differentiation (CD)4?single positive (SP) T cells
      and decreased the proportions of CD8?SP, CD4+ V?8.2+ and CD8+ V?8.2+ T cells in
      the thymus of neonatal rats between day 0 and 5 after delivery. In an in vitro
      cultured thymus, SEB restimulation significantly increased the proportion of
      double positive cells and decreased the proportions of CD4?SP, CD8?SP, CD4+
      V?8.2+ and CD8+ V?8.2+ T cells. Furthermore, the decreased V?8.2+ T?cells in
      neonatal rats exposed prenatally to SEB were further deleted by SEB restimulation
      in an in vitro cultured thymus. These data suggested the special response pattern
      of the remaining SEB?specific T cells to SEB restimulation in neonatal rats
      exposed prenatally to SEB. 

PMID- 24865815
TI  - High prevalence of Ancylostoma ceylanicum hookworm infections in humans,
      Cambodia, 2012.
AB  - Ancylostoma ceylanicum, a hookworm of canids and felids in Asia, is becoming the
      second most common hookworm infecting humans. In 2012, we investigated the
      prevalence and infection dynamics of and risk factors for hookworm infections in
      humans and dogs in a rural Cambodian village. Over 57% of the population was
      infected with hookworms; of those, 52% harbored A. ceylanicum hookworms. The
      greatest intensities of A. ceylanicum eggs were in persons 21-30 years of age.
      Over 90% of dogs also harbored A. ceylanicum hookworms. Characterization of the
      cytochrome oxidase-1 gene divided isolates of A. ceylanicum hookworms into 2
      groups, 1 containing isolates from humans only and the other a mix of isolates
      from humans and animals. We hypothesize that preventative chemotherapy in the
      absence of concurrent hygiene and animal health programs may be a factor leading
      to emergence of A. ceylanicum infections; thus, we advocate for a One Health
      approach to control this zoonosis. 

PMID- 24865817
TI  - Ultrasensitive detection of transcription factors using transcription-mediated
      isothermally exponential amplification-induced chemiluminescence.
AB  - Transcription factors (TFs) are important cellular components that modulate gene
      expression, and the malregulation of transcription will lead to a variety of
      diseases such as cancer and developmental syndromes. However, the conventional
      methods for transcription factor assay are generally cumbersome and costly with
      low sensitivity. Here, we develop a label-free strategy for ultrasensitive
      detection of transcription factors using a cascade signal amplification of RNA
      transcription, dual isothermally exponential amplification reaction (EXPAR), and
      G-quadruplex DNAzyme-driven chemiluminescence. Briefly, the specific binding of
      TF with the detecting probe prevents the cleavage of the detecting probe by
      exonuclease and subsequently facilitates the conversion of TF signal to abundant
      RNA triggers in the presence of T7 RNA polymerase. The obtained RNA triggers can
      initiate the strand displacement amplification to yield abundant DNAzymes and DNA
      triggers, and the released DNA triggers can further initiate the next rounds of
      EXPAR reaction. The synergistic operation of dual EXPAR reaction can produce
      large amounts of DNAzymes, which subsequently catalyze the oxidation of luminol
      by H2O2 to yield an enhanced chemiluminescence signal with the assistance of
      cofactor hemin. Conversely, in the absence of target TF, the naked detecting
      probes will be completely digested by exonucleases, leading to neither the
      transcription-mediated EXPAR nor the DNAzyme-driven chemiluminescence signal.
      This method has a low detection limit of as low as 6.03 * 10(-15) M and a broad
      dynamic range from 10 fM to 1 nM and can even measure the NF-kappaB p50 of crude
      cell nuclear extracts. Moreover, this method can be used to measure a variety of
      DNA-binding proteins by simply substituting the target-specific binding sequence
      in the detecting probes. 

PMID- 24865818
TI  - A large-scale field assessment of carbon stocks in human-modified tropical
      forests.
AB  - Tropical rainforests store enormous amounts of carbon, the protection of which
      represents a vital component of efforts to mitigate global climate change.
      Currently, tropical forest conservation, science, policies, and climate
      mitigation actions focus predominantly on reducing carbon emissions from
      deforestation alone. However, every year vast areas of the humid tropics are
      disturbed by selective logging, understory fires, and habitat fragmentation.
      There is an urgent need to understand the effect of such disturbances on carbon
      stocks, and how stocks in disturbed forests compare to those found in undisturbed
      primary forests as well as in regenerating secondary forests. Here, we present
      the results of the largest field study to date on the impacts of human
      disturbances on above and belowground carbon stocks in tropical forests. Live
      vegetation, the largest carbon pool, was extremely sensitive to disturbance:
      forests that experienced both selective logging and understory fires stored, on
      average, 40% less aboveground carbon than undisturbed forests and were
      structurally similar to secondary forests. Edge effects also played an important
      role in explaining variability in aboveground carbon stocks of disturbed forests.
      Results indicate a potential rapid recovery of the dead wood and litter carbon
      pools, while soil stocks (0-30 cm) appeared to be resistant to the effects of
      logging and fire. Carbon loss and subsequent emissions due to human disturbances
      remain largely unaccounted for in greenhouse gas inventories, but by comparing
      our estimates of depleted carbon stocks in disturbed forests with Brazilian
      government assessments of the total forest area annually disturbed in the Amazon,
      we show that these emissions could represent up to 40% of the carbon loss from
      deforestation in the region. We conclude that conservation programs aiming to
      ensure the long-term permanence of forest carbon stocks, such as REDD+, will
      remain limited in their success unless they effectively avoid degradation as well
      as deforestation. 

PMID- 24865819
TI  - Ligand entry into the calyx of beta-lactoglobulin.
AB  - Although the thermodynamic principles that control the binding of drug molecules
      to their protein targets are well understood, the detailed process of how a
      ligand reaches a protein binding site has been an intriguing question over
      decades. The short time interval between the encounter between a ligand and its
      receptor to the formation of the stable complex has prevented experimental
      observations. Bovine beta-lactoglobulin (betalg) is a lipocalin member that
      carries fatty acids (FAs) and other lipids in the cellular environment. Betalg
      accommodates a FA molecule in its highly hydrophobic cavity and exhibits the
      capability of recognizing a wide variety of hydrophobic ligands. To elucidate the
      ligand entry process on betalg, we report molecular dynamics simulations of the
      encounter between palmitate (PA) or laurate (LA) and betalg. Our results show
      that residues localized in loops at the cavity entrance play an important role in
      the ligand penetration process. Analysis of the short-term interaction energies
      show that the forces operating on the systems lead to average conformations very
      close to the crystallographic holo-forms. Whereas the binding free energy
      analysis using the molecular mechanics Generalized Born surface area method shows
      that these conformations were thermodynamically favorable.

PMID- 24865820
TI  - Allosteric transitions of the maltose transporter studied by an elastic network
      model.
AB  - The maltose transporter from Escherichia coli is one of the ATP-binding cassette
      (ABC) transporters that utilize the energy from ATP hydrolysis to translocate
      substrates across cellular membranes. Until 2011, three crystal structures have
      been determined for maltose transporter at different states in the process of
      transportation. Here, based on these crystal structures, the allosteric pathway
      from the resting state (inward-facing) to the catalytic intermediate state
      (outward-facing) is studied by applying an adaptive anisotropic network model.
      The results suggest that the allosteric transitions proceed in a coupled way. The
      closing of the nucleotide-binding domains occurs first, and subsequently this
      conformational change is propagated to the transmembrane domains (TMD) via the
      EAA and EAS loops, and then to the maltose-binding protein, which facilitates the
      translocation of the maltose. It is also found that there exist nonrigid-body and
      asymmetric movements in the TMD. The cytoplasmic gate may only play the role of
      allosteric propagation during the transition from the pretranslocation to outward
      facing states. In addition, the results show that the movment of the helical
      subdomain towards the RecA-like subdomain mainly occurs in the earlier stages of
      the transition. These results can provide some insights into the understanding of
      the mechanism of ABC transporters.

PMID- 24865821
TI  - Risk of acute liver injury associated with the use of moxifloxacin and other oral
      antimicrobials: a retrospective, population-based cohort study.
AB  - STUDY OBJECTIVE: To estimate the incidence and relative risk of a hospitalization
      or emergency visit for noninfectious liver injury in users of eight oral
      antimicrobials-amoxicillin, amoxicillin-clavulanic acid, clarithromycin,
      cefuroxime, doxycycline, levofloxacin, moxifloxacin, telithromycin-compared with
      nonusers of these antimicrobials. DESIGN: Retrospective, observational cohort
      study with a nested case-control analysis. DATA SOURCE: HealthCore Integrated
      Research Database. PATIENTS: Adults with continuous health plan enrollment for at
      least 6 months before study entry who had a new dispensing of a study
      antimicrobial between July 1, 2001, and March 31, 2009. Cases had diagnoses
      indicating noninfectious liver injury during follow-up. To control for
      potentially confounding risk factors, 10 controls at risk for liver injury during
      follow-up were matched to each case by age, sex, and event date (liver injury
      date of the case), and analyses were adjusted for medical history, concomitant
      drugs, and health care service use. MEASUREMENTS AND MAIN RESULTS: Two physician
      reviewers (blind to exposure) validated the cases. Among 1.3 million
      antimicrobial users, we identified 607 cases of liver injury, including 82 cases
      of severe hepatocellular injury and 11 cases of liver failure. Liver injury
      incidence in nonusers of study antimicrobials was 35/100,000 person-years (95%
      confidence interval [CI] 29-42/100,000 person-years). For valid cases, the
      adjusted relative risk among current users of multiple antimicrobials was 3.2
      (95% CI 1.6-6.7). Levofloxacin had the highest relative risk for current single
      use (3.2, 95% CI 1.8-5.8). Relative risks were also elevated for amoxicillin
      clavulanic acid (2.5, 95% CI 1.3-5.0), doxycycline (2.5, 95% CI 1.2-5.2),
      moxifloxacin (2.3, 95% CI 1.1-4.7), and amoxicillin (2.3, 95% CI 1.1-4.7).
      CONCLUSION: The results support a comparatively high adjusted relative risk of
      liver injury among patients exposed concurrently to multiple antimicrobials and
      modest elevations in the risk for several antimicrobials used alone; however, we
      found little evidence of any strong effect of commonly used antimicrobials on the
      risk of liver injury.

PMID- 24865822
TI  - Splenic hamartomas in Alagille syndrome: case report and literature review.
AB  - Alagille syndrome is a rare autosomal dominant disorder with characteristic
      findings of paucity of intrahepatic bile ducts, congenital heart disease, and
      vertebral, ocular, and renal abnormalities. We present a unique autopsy case of
      an 18-year-old female with Alagille syndrome and splenic hamartomas. Autopsy
      findings included growth restriction, Tetralogy of Fallot, paucity of
      intrahepatic bile ducts, end-stage renal disease with mesangiolipidosis, and
      splenomegaly with two well-circumscribed, splenic tumors. Histologic findings of
      the splenic tumors revealed disorganized vascular channels lined by cells without
      cytologic atypia. Immunohistochemical analysis demonstrated CD8(+)CD31(+)
      endothelial cells, consistent with splenic hamartomas. In summary, Alagille
      syndrome is a rare genetic disorder characterized by JAG1 mutations and disrupted
      Notch signaling. Review of the literature highlights the importance of Notch
      signaling in vascular development and disorders. However, to our knowledge this
      is the first description of splenic hamartomas in Alagille syndrome. 

PMID- 24865823
TI  - Unique giant cardiac tumor in an infant: rhabdomyoma or fibroma?
AB  - We report a case of giant cardiac tumor diagnosed at fetal life and thought to be
      a fibroma. Six months later, a marked regression of the tumor size was observed.
      Diagnosis of rhabdomyoma was retrospectively made. Tuberous sclerosis was then
      suspected and MRI showed many signs of consistent diagnosis. 

PMID- 24865824
TI  - A knock on the door.

PMID- 24865825
TI  - A proposal to reduce misrepresentation of medical student research activities in
      ERAS.

PMID- 24865826
TI  - In reply to Grimm and Maxfield.

PMID- 24865827
TI  - Addressing concerns about a "core + clusters" physical exam.

PMID- 24865828
TI  - To the editor.

PMID- 24865829
TI  - In reply to Gowda et al and to Yudkowsky.

PMID- 24865830
TI  - In reply to Yudkowsky.

PMID- 24865831
TI  - While we advocate for integrated electronic medical records, continue to empower
      patients and families.

PMID- 24865833
TI  - Artist's statement: Personal statement.

PMID- 24865832
TI  - In reply to Daggett.

PMID- 24865834
TI  - Medicine and the arts. Commentary on Illness as Metaphor [excerpt] by Susan
      Sontag.

PMID- 24865835
TI  - Compassion and my cadaver.

PMID- 24865836
TI  - Deep listening.

PMID- 24865837
TI  - Hair-inspired crystal growth of HOA in cavities of cellulose matrix via
      hydrophobic-hydrophilic interface interaction.
AB  - As one of the most ordinary phenomena in nature, numerous pores on animal skins
      induce the growth of abundant hairs. In this study, cavities of a cellulose
      matrix were used as hard templates to lead the hair-inspired crystal growth of 12
      hydroxyoctadecanoic acid (HOA) through hydrophobic-hydrophilic interface
      interaction, and short hair-like HOA crystals with a smooth surface were formed
      on cellulose films. In our findings, by using solvent evaporation induced
      crystallization, hydrophobic HOA grew along the hydrophilic cellulose pore wall
      to form regular vertical worm-like and pillar-like crystals with an average
      diameter of about 200 nm, depending on the experimental conditions and HOA
      concentration. The formation mechanism of the short hair-like HOA crystals as
      well as the structure and properties of the cellulose/HOA submicrometer composite
      films were studied. The pores of the cellulose matrix supplied not only cavities
      for the HOA crystals fixation but also hydrophilic shells to favor the vertical
      growth of the relatively hydrophobic HOA crystals. The cellulose/HOA
      submicrometer composite films exhibited high hydrophobicity, as a result of the
      formation of the solid/air composite surface. Furthermore, 4-(1,2,2
      triphenylethenyl) benzoic acid, an aggregation-induced emission luminogen, was
      used to aggregate on the cellulose surface with HOA to emit and monitor the HOA
      crystal growth, showing bifunctional photoluminscence and self-cleaning
      properties. This work opens up a novel one-step pathway to design bio-inspired
      submicrometer materials by utilizing natural products, showing potential
      applications in self-cleaning optical devices. 

PMID- 24865840
TI  - Switching hydrodynamics in liquid crystal devices: a simulation perspective.
AB  - In liquid crystal devices it is important to understand the physics underlying
      their switching between different states, which is usually achieved by applying
      or removing an electric field. Flow is known to be a key determinant of the
      timescales and pathways of the switching kinetics. Incorporating hydrodynamic
      effects into theories for liquid crystal devices is therefore important; however
      this is also highly non-trivial, and typically requires the use of accurate
      numerical methods. Here, we review some recent advances in our theoretical
      understanding of the dynamics of switching in liquid crystal devices, mainly
      gained through computer simulations. These results, as we shall show, uncover
      interesting new physics, and may be important for future applications. 

PMID- 24865838
TI  - Clusterin is a potential lymphotoxin beta receptor target that is upregulated and
      accumulates in germinal centers of mouse spleen during immune response.
AB  - Clusterin is a multifunctional protein that participates in tissue remodeling,
      apoptosis, lipid transport, complement-mediated cell lysis and serves as an
      extracellular chaperone. The role of clusterin in cancer and neurodegeneration
      has been extensively studied, however little is known about its functions in the
      immune system. Using expression profiling we found that clusterin mRNA is
      considerably down-regulated in mouse spleen stroma upon knock-out of lymphotoxin
      beta receptor which plays pivotal role in secondary lymphoid organ development,
      maintenance and function. Using immunohistochemistry and western blot we studied
      clusterin protein level and distribution in mouse spleen and mesenteric lymph
      nodes in steady state and upon immunization with sheep red blood cells. We showed
      that clusterin protein, represented mainly by the secreted heterodimeric form, is
      present in all stromal compartments of secondary lymphoid organs except for
      marginal reticular cells. Clusterin protein level rose after immunization and
      accumulated in light zones of germinal centers in spleen--the effect that was not
      observed in lymph nodes. Regulation of clusterin expression by the lymphotoxin
      beta signaling pathway and its protein dynamics during immune response suggest a
      specific role of this enigmatic protein in the immune system that needs further
      study.

PMID- 24865841
TI  - Profile sampling to characterize particulate lead risks in potable water.
AB  - Traditional lead (Pb) profiling, or collecting sequential liters of water that
      flow from a consumer tap after a stagnation event, has recently received
      widespread use in understanding sources of Pb in drinking water and risks to
      consumer health, but has limitations in quantifying particulate Pb risks. A new
      profiling protocol was developed in which a series of traditional profiles are
      collected from the same tap at escalating flow rates. The results revealed marked
      differences in risks of Pb exposure from one consumer home to another as a
      function of flow rate, with homes grouped into four risk categories with
      differing flushing requirements and public education to protect consumers. On
      average, Pb concentrations detected in water at high flow without stagnation were
      at least three to four times higher than in first draw samples collected at low
      flow with stagnation, demonstrating a new "worst case" lead release scenario,
      contrary to the original regulatory assumption that stagnant, first draw samples
      contain the highest lead concentrations. Testing also revealed that in some cases
      water samples with visible particulates had much higher Pb than samples without
      visible particulates, and tests of different sample handling protocols confirmed
      that some EPA-allowed methods would not quantify as much as 99.9% of the Pb
      actually present (avg. 27% of Pb not quantified). 

PMID- 24865842
TI  - Routine pre-operative focused ultrasonography by anesthesiologists in patients
      undergoing urgent surgical procedures.
AB  - BACKGROUND: Unexpected cardiopulmonary complications are well described during
      surgery and anesthesia. Pre-operative evaluation by focused cardiopulmonary
      ultrasonography may prevent such mishaps. The aim of this study was to determine
      the frequency of unexpected cardiopulmonary pathology with focused
      ultrasonography in patients undergoing urgent surgical procedures. METHODS: We
      performed pre-operative focused cardiopulmonary ultrasonography in patients aged
      18 years or above undergoing urgent surgical procedures at pre-defined study
      days. Known and unexpected cardiopulmonary pathology was recorded, and subsequent
      changes in the anesthesia technique or supportive actions were registered.
      RESULTS: A total of 112 patients scheduled for urgent surgical procedures were
      included. Their mean age (standard deviation) was 62 (21) years. Of these
      patients, 24% were American Society of Anesthesiologists (ASA) class 1, 39% were
      ASA class 2, 32% were ASA class 3, and 4% were ASA class 4. Unexpected
      cardiopulmonary pathology was disclosed in 27% [95% confidence interval (CI) 19
      36] of the patients and led to a change in anesthesia technique or supportive
      actions in 43% (95% CI 25-63) of these. Unexpected pathology leading to changes
      in anesthesia technique or supportive actions was only disclosed in a group of
      patients above the age of 60 years and/or in ASA class >= 3. CONCLUSION: Focused
      cardiopulmonary ultrasonography disclosed unexpected pathology in patients
      undergoing urgent surgical procedures and induced changes in the anesthesia
      technique or supportive actions. Pre-operative focused ultrasonography seems
      feasible in patients above 60 year and/or with physical limitations but not in
      young, healthy individuals.

PMID- 24865843
TI  - Vesicles composed of one simple single-tailed surfactant.
AB  - Novel vesicles formed spontaneously from the micelle solution of DTAB, a single
      tailed surfactant (STS), mediated by a rough glass surface (RGS) without any
      additives. The obtained STS vesicles displayed good stability upon long-term
      storage, exposure to high temperatures, and freeze-thawing after the removal of
      RGS. 

PMID- 24865844
TI  - Investigating the dynamic aspects of drug-protein recognition through a
      combination of MD and NMR analyses: implications for the development of protein
      protein interaction inhibitors.
AB  - In this paper, we investigate the dynamic aspects of the molecular recognition
      between a small molecule ligand and a flat, exposed protein surface, representing
      a typical target in the development of protein-protein interaction inhibitors.
      Specifically, we analyze the complex between the protein Fibroblast Growth Factor
      2 (FGF2) and a recently discovered small molecule inhibitor, labeled sm27 for
      which the binding site and the residues mainly involved in small molecule
      recognition have been previously characterized. We have approached this problem
      using microsecond MD simulations and NMR-based characterizations of the dynamics
      of the apo and holo states of the system. Using direct combination and cross
      validation of the results of the two techniques, we select the set of
      conformational states that best recapitulate the principal dynamic and structural
      properties of the complex. We then use this information to generate a multi
      structure representation of the sm27-FGF2 interaction. We propose this kind of
      representation and approach as a useful tool in particular for the
      characterization of systems where the mutual dynamic influence between the
      interacting partners is expected to play an important role. The results presented
      can also be used to generate new rules for the rational expansion of the chemical
      diversity space of FGF2 inhibitors. 

PMID- 24865847
TI  - New insight in the structural features of haloadaptation in alpha-amylases from
      halophilic Archaea following homology modeling strategy: folded and stable
      conformation maintained through low hydrophobicity and highly negative charged
      surface.
AB  - Proteins from halophilic archaea, which live in extreme saline conditions, have
      evolved to remain folded, active and stable at very high ionic strengths.
      Understanding the mechanism of haloadaptation is the first step toward
      engineering of halostable biomolecules. Amylases are one of the main enzymes used
      in industry. Yet, no three-dimensional structure has been experimentally resolved
      for alpha-amylases from halophilic archaea. In this study, homology structure
      modeling of alpha-amylases from the halophilic archaea Haloarcula marismortui,
      Haloarcula hispanica, and Halalkalicoccus jeotgali were performed. The resulting
      models were subjected to energy minimization, evaluation, and structural
      analysis. Calculations of the amino acid composition, salt bridges and
      hydrophobic interactions were also performed and compared to a set of non
      halophilic counterparts. It clearly appeared that haloarchaeal alpha-amylases
      exhibited lower propensities for helix formation and higher propensities for coil
      forming regions. Furthermore, they could maintain a folded and stable
      conformation in high salt concentration through highly negative charged surface
      with over representation of acidic residues, especially Asp, and low
      hydrophobicity with increase of salt bridges and decrease in hydrophobic
      interactions on the protein surface. This study sheds some light on the stability
      of alpha-amylases from halophilic archaea and provides strong basis not only to
      understand haloadaptation mechanisms of proteins in microorganisms from
      hypersalines environments but also for biotechnological applications. 

PMID- 24865846
TI  - Network analyses reveal pervasive functional regulation between proteases in the
      human protease web.
AB  - Proteolytic processing is an irreversible posttranslational modification
      affecting a large portion of the proteome. Protease-cleaved mediators frequently
      exhibit altered activity, and biological pathways are often regulated by
      proteolytic processing. Many of these mechanisms have not been appreciated as
      being protease-dependent, and the potential in unraveling a complex new dimension
      of biological control is increasingly recognized. Proteases are currently
      believed to act individually or in isolated cascades. However, conclusive but
      scattered biochemical evidence indicates broader regulation of proteases by
      protease and inhibitor interactions. Therefore, to systematically study such
      interactions, we assembled curated protease cleavage and inhibition data into a
      global, computational representation, termed the protease web. This revealed that
      proteases pervasively influence the activity of other proteases directly or by
      cleaving intermediate proteases or protease inhibitors. The protease web spans
      four classes of proteases and inhibitors and so links both recently and
      classically described protease groups and cascades, which can no longer be viewed
      as operating in isolation in vivo. We demonstrated that this observation, termed
      reachability, is robust to alterations in the data and will only increase in the
      future as additional data are added. We further show how subnetworks of the web
      are operational in 23 different tissues reflecting different phenotypes. We
      applied our network to develop novel insights into biologically relevant protease
      interactions using cell-specific proteases of the polymorphonuclear leukocyte as
      a system. Predictions from the protease web on the activity of matrix
      metalloproteinase 8 (MMP8) and neutrophil elastase being linked by an
      inactivating cleavage of serpinA1 by MMP8 were validated and explain perplexing
      Mmp8-/- versus wild-type polymorphonuclear chemokine cleavages in vivo. Our
      findings supply systematically derived and validated evidence for the existence
      of the protease web, a network that affects the activity of most proteases and
      thereby influences the functional state of the proteome and cell activity. 

PMID- 24865848
TI  - Temperature effect on poly(dA).poly(dT): molecular dynamics simulation studies of
      polymeric and oligomeric constructs.
AB  - Understanding unwinding and melting of double helical DNA is very important to
      characterize role of DNA in replication, transcription, translation etc. Sequence
      dependent melting thermodynamics is used extensively for detecting promoter
      regions but melting studies are generally done for short oligonucleotides. This
      study reports several molecular dynamics (MD) simulations of homopolymeric
      poly(dA).poly(dT) as regular oligonucleotide fragments as well as its
      corresponding polymeric constructs with water and charge-neutralizing counterions
      at different temperatures ranging from 300 to 400 K. We have eliminated the end
      effect or terminal peeling propensity by employing MD simulation of DNA
      oligonucleotides in such a manner that gives rise to properties of polymeric DNA
      of infinite length. The dynamic properties such as basepairing and stacking
      geometry, groove width, backbone conformational parameters, bending, distribution
      of counter ions and number of hydrogen bonds of oligomeric and polymeric
      constructs of poly(dA).poly(dT) have been analyzed. The oligomer shows terminal
      fraying or peeling effect at temperatures above 340 K. The polymer shows partial
      melting at elevated temperatures although complete denaturations of basepairs do
      not take place. The analysis of cross strand hydrogen bonds shows that the number
      of N-H...O hydrogen bonds increases with increase in temperature while C-H...O
      hydrogen bond frequencies decrease with temperature. Restructuring of counterions
      in the minor groove with temperature appear as initiation of melting in duplex
      structures. 

PMID- 24865849
TI  - An emergency room decision-support program that increased physician office
      visits, decreased emergency room visits, and saved money.
AB  - The objective of this study was to evaluate an Emergency Room having a Decision
      Support (ERDS) program designed to appropriately reduce ER use among frequent
      users, defined as 3 or more visits within a 12-month period. To achieve this,
      adults with an AARP Medicare Supplement Insurance plan insured by
      UnitedHealthcare Insurance Company (for New York residents, UnitedHealthcare
      Insurance Company of New York) were eligible to participate in the program. These
      included 7070 individuals who elected to enroll in the ERDS program and an equal
      number of matched nonparticipants who were eligible but either declined or were
      unreachable. Program-related benefits were estimated by comparing the difference
      in downstream health care utilization and expenditures between engaged and not
      engaged individuals after using propensity score matching to adjust for case mix
      differences between these groups. As a result, compared with the not engaged,
      engaged individuals experienced better care coordination, evidenced by a greater
      reduction in ER visits (P=0.033) and hospital admissions (P=0.002) and an
      increase in office visits (P<0.001). The program was cost-effective, with a
      return on investment (ROI) of 1.24, which was calculated by dividing the total
      program savings ($3.41 million) by the total program costs ($2.75 million). The
      ROI implies that for every dollar invested in this program, $1.24 was saved, most
      of which was for the federal Medicare program. In conclusion, the decrease in ER
      visits and hospital admissions and the increase in office visits may indicate the
      program helped individuals to seek the appropriate levels of care.

PMID- 24865851
TI  - Barriers, biases, and beliefs about arteriovenous fistula placement in children:
      a survey of the International Pediatric Fistula First Initiative (IPFFI) within
      the Midwest Pediatric Nephrology Consortium (MWPNC).
AB  - There has been recent emphasis on increased arteriovenous fistula (AVF) use and
      decreased central venous catheter use in hemodialysis (HD) patients. The
      International Pediatric Fistula First Initiative was founded via collaborative
      effort with the Midwest Pediatric Nephrology Consortium to alert nephrologists,
      surgeons, and dialysis staff to consider fistulae as the best access in pediatric
      HD patients. A multidisciplinary educational DVD outlining expectations and
      strategies to increase AVF placement and usage in children was created.
      Participants were administered a survey previewing and postviewing to identify
      barriers to placement and usage of AVF in children. A total of 52 surveys were
      subdivided as either "dialysis staff" or "proceduralist" at five centers. Thirty
      three percent of respondents were unaware if their practice was following
      published guidelines. Sixty-five percent of respondents stated they referred to a
      dedicated vascular access surgeon at their respective institutions. Methods used
      to monitor AVF function included physical exam, venous pressure monitoring, and
      ultrasound dilution. Vascular access was placed within 3 months in only 35% of
      patients. Interdisciplinary communication problems between surgeons,
      interventional radiologists, and nephrologists were identified as a major
      barrier. Lack of AVF usage was often due to maturation failure. Routine access
      rounds did not occur in any centers. Regarding monitoring, 74% of the respondents
      use physical exam, 26% use venous pressure monitoring, and 9% use ultrasound
      dilution. Ninety-three percent of dialysis staff stated they would change
      practice patterns following the intervention; however, 12% of surgeons stated
      they would alter practice patterns. To our knowledge, this is the first report to
      identify barriers to placement of AVF in children from the perspectives of
      multidisciplinary team members including pediatric nephrologists, surgeons,
      interventional radiologists, and multidisciplinary dialysis staff. 

PMID- 24865856
TI  - Excellent anti-fogging dye-sensitized solar cells based on superhydrophilic
      nanoparticle coatings.
AB  - We present a facile method for producing anti-fogging (AF) and anti-reflection
      (AR) coating functionalized photoanodes via one-step SiO2 nanoparticle coating
      for high performance solid state dye-sensitized solar cells (ssDSSCs). The AF and
      AR coating functionalized photoanodes are prepared by spin-coating of partially
      aggregated SiO2 colloidal solution. Poly((1-(4-ethenylphenyl)methyl)-3-butyl
      imidazolium iodide) (PEBII), prepared via free radical polymerization, is used as
      a solid electrolyte in I2-free ssDSSCs. We systematically investigate the
      enhanced light harvesting characteristics of AF and AR coating functionalized
      photoanode-based ssDSSCs by measuring UV-visible spectroscopy, incident photon-to
      electron conversion efficiency (IPCE) curves under fogging conditions. Compared
      with conventional photoanode based ssDSSCs, the AF and AR coating functionalized
      photoanodes substantially suppress fogging and reduce reflection, leading to
      significantly enhanced light harvesting, especially under fogging conditions.
      ssDSSCs made of AF and AR coating functionalized photoanodes exhibit an improved
      photovoltaic efficiency of 6.0% and 5.9% under non-fogging and fogging
      conditions, respectively, and retain their device efficiencies for at least 20
      days, which is a significant improvement of ssDSSCs with conventional photoanodes
      (4.7% and 1.9% under non-fogging and fogging conditions, respectively). We
      believe that AF and AR functionalization via one-step SiO2 colloidal coating is a
      promising method for enhancing light harvesting properties in various solar
      energy conversion applications. 

PMID- 24865854
TI  - Dysregulated miR-361-5p/VEGF axis in the plasma and endothelial progenitor cells
      of patients with coronary artery disease.
AB  - Dysfunction and reduction of circulating endothelial progenitor cell (EPC) is
      correlated with the onset of cardiovascular disorders including coronary artery
      disease (CAD). VEGF is a known mitogen for EPC to migrate out of bone marrow to
      possess angiogenic activities, and the plasma levels of VEGF are inversely
      correlated to the progression of CAD. Circulating microRNAs (miRNAs) in patient
      body fluids have recently been considered to hold the potential of being novel
      disease biomarkers and drug targets. However, how miRNAs and VEGF cooperate to
      regulate CAD progression is still unclear. Through the small RNA sequencing
      (smRNA-seq), we deciphered the miRNome patterns of EPCs with different angiogenic
      activities, hypothesizing that miRNAs targeting VEGF must be more abundant in
      EPCs with lower angiogenic activities. Candidates of anti-VEGF miRNAs, including
      miR-361-5p and miR-484, were enriched in not only diseased EPCs but also the
      plasma of CAD patients. However, we found out only miR-361-5p, but not miR-484,
      was able to suppress VEGF expression and EPC activities. Reporter assays
      confirmed the direct binding and repression of miR-361-5p to the 3'-UTR of VEGF
      mRNA. Knock down of miR-361-5p not only restored VEGF levels and angiogenic
      activities of diseased EPCs in vitro, but further promoted blood flow recovery in
      ischemic limbs of mice. Collectively, we discovered a miR-361-5p/VEGF-dependent
      regulation that could help to develop new therapeutic modalities not only for
      ischemia-related diseases but also for tumor angiogenesis. 

PMID- 24865855
TI  - High incidence of norovirus GII.4 outbreaks in hospitals and nursing homes in
      Catalonia (Spain), 2010-2011.
AB  - A descriptive study was performed between 1 January 2010 and 31 December 2011 to
      estimate the incidence of norovirus outbreaks in hospitals and nursing homes in
      Catalonia (Spain). Epidemiological surveys were done for each outbreak. Norovirus
      was confirmed using RT-PCR. The incidence of outbreaks/106 person-years by
      centre, and the attack rate, were calculated. Statistically significant
      differences were calculated using odds ratio (ORs) and 95% confidence intervals
      (CIs). Person-to-person transmission was responsible for 81.5% (22/27) of
      outbreaks. The incidence in the population was 156.7 outbreaks/106 person-years.
      The incidence by centre was 1.3% per year and was greater in hospitals (2.6%)
      than in nursing homes (0.9%) (OR 3.2, 95% CI 1.5-6.9). The global attack rate in
      residents and staff was 34.7% (816/2348). The mortality rate was 0.25% (2/816).
      Genogroup GII.4 caused 66.7% of outbreaks. Norovirus GII.4 outbreaks cause
      significant morbidity affecting both patients and staff.

PMID- 24865853
TI  - Ubiquitin ligase ITCH recruitment suppresses the aggregation and cellular
      toxicity of cytoplasmic misfolded proteins.
AB  - The protein quality control (QC) system protects cells against cellular toxicity
      induced by misfolded proteins and maintains overall cellular fitness. Inefficient
      clearance of or failure to degrade damaged proteins causes several diseases,
      especially age-linked neurodegenerative disorders. Attenuation of misfolded
      protein degradation under severe stress conditions leads to the rapid over
      accumulation of toxic proteinaceous aggregates in the cytoplasmic compartment.
      However, the precise cytoplasmic quality control degradation mechanism is
      unknown. In the present study, we demonstrate that the Nedd4-like E3 ubiquitin
      ligase ITCH specifically interacts with mutant bona fide misfolded proteins and
      colocalizes with their perinuclear aggregates. In a cell culture model, we
      demonstrate ITCH recruitment by cytoplasmic inclusions containing polyglutamine
      expanded huntingtin or ataxin-3 proteins. Transient overexpression of ITCH
      dramatically induced the degradation of thermally denatured misfolded luciferase
      protein. Partial depletion of ITCH increased the rate of aggregate formation and
      cell death generated by expanded polyglutamine proteins. Finally, we demonstrate
      that overexpression of ITCH alleviates the cytotoxic potential of expanded
      polyglutamine proteins and reduces aggregation. These observations indicate that
      ITCH is involved in the cytosolic quality control pathway and may help to explain
      how abnormal proteins are targeted by QC ubiquitin-protein ligases. 

PMID- 24865858
TI  - Integrated image data and medical record management for rare disease registries.
      A general framework and its instantiation to theGerman Calciphylaxis Registry.
AB  - Especially for investigator-initiated research at universities and academic
      institutions, Internet-based rare disease registries (RDR) are required that
      integrate electronic data capture (EDC) with automatic image analysis or manual
      image annotation. We propose a modular framework merging alpha-numerical and
      binary data capture. In concordance with the Office of Rare Diseases Research
      recommendations, a requirement analysis was performed based on several RDR
      databases currently hosted at Uniklinik RWTH Aachen, Germany. With respect to the
      study management tool that is already successfully operating at the Clinical
      Trial Center Aachen, the Google Web Toolkit was chosen with Hibernate and Gilead
      connecting a MySQL database management system. Image and signal data integration
      and processing is supported by Apache Commons FileUpload-Library and ImageJ-based
      Java code, respectively. As a proof of concept, the framework is instantiated to
      the German Calciphylaxis Registry. The framework is composed of five mandatory
      core modules: (1) Data Core, (2) EDC, (3) Access Control, (4) Audit Trail, and
      (5) Terminology as well as six optional modules: (6) Binary Large Object (BLOB),
      (7) BLOB Analysis, (8) Standard Operation Procedure, (9) Communication, (10)
      Pseudonymization, and (11) Biorepository. Modules 1-7 are implemented in the
      German Calciphylaxis Registry. The proposed RDR framework is easily instantiated
      and directly integrates image management and analysis. As open source software,
      it may assist improved data collection and analysis of rare diseases in near
      future. 

PMID- 24865859
TI  - Multi-resolution level sets with shape priors: a validation report for 2D
      segmentation of prostate gland in T2W MR images.
AB  - The level set approach to segmentation of medical images has received
      considerable attention in recent years. Evolving an initial contour to converge
      to anatomical boundaries of an organ or tumor is a very appealing method,
      especially when it is based on a well-defined mathematical foundation. However,
      one drawback of such evolving method is its high computation time. It is
      desirable to design and implement algorithms that are not only accurate and
      robust but also fast in execution. Bresson et al. have proposed a variational
      model using both boundary and region information as well as shape priors. The
      latter can be a significant factor in medical image analysis. In this work, we
      combine the variational model of level set with a multi-resolution approach to
      accelerate the processing. The question is whether a multi-resolution context can
      make the segmentation faster without affecting the accuracy. As well, we
      investigate the question whether a premature convergence, which happens in a much
      shorter time, would reduce accuracy. We examine multiple semiautomated
      configurations to segment the prostate gland in T2W MR images. Comprehensive
      experimentation is conducted using a data set of a 100 patients (1,235 images) to
      verify the effectiveness of the multi-resolution level set with shape priors. The
      results show that the convergence speed can be increased by a factor of ~ 2.5
      without affecting the segmentation accuracy. Furthermore, a premature convergence
      approach drastically increases the segmentation speed by a factor of ~ 17.9. 

PMID- 24865860
TI  - Efficacy of a checklist-style structured radiology reporting template in reducing
      resident misses on cervical spine computed tomography examinations.
AB  - The increasing use of medical checklists to promote patient safety raises the
      question of their utility in diagnostic radiology. This study evaluates the
      efficacy of a checklist-style reporting template in reducing resident misses on
      cervical spine CT examinations. A checklist-style reporting template for cervical
      spine CTs was created at our institution and mandated for resident preliminary
      reports. Ten months after implementation of the template, we performed a
      retrospective cohort study comparing rates of emergent pathology missed on
      reports generated with and without the checklist-style reporting template. In
      1,832 reports generated without using the checklist-style template, 25 (17.6%)
      out of 142 emergent findings were missed. In 1,081 reports generated using the
      checklist-style template, 13 (11.9%) out of 109 emergent findings were missed.
      The decrease in missed pathology was not statistically significant (p = 0.21).
      However, larger differences were noted in the detection of emergent non-fracture
      findings, with 17 (28.3%) out of 60 findings missed on reports without use of the
      checklist template and 5 (9.3%) out of 54 findings missed on reports using the
      checklist template, representing a statistically significant decrease in missed
      non-fracture findings (p = 0.01). The use of a checklist-style structured
      reporting template resulted in a statistically significant decrease in missed non
      fracture findings on cervical spine CTs. The lack of statistically significant
      change in missed fractures was expected given that residents' search patterns
      naturally include fracture detection. Our findings suggest that the use of
      checklists in structured reporting may increase diagnostic accuracy.

PMID- 24865861
TI  - Metabolites from thermophilic bacteria I: N-propionylanthranilic acid, a co
      metabolite of the bacillamide class antibiotics and tryptophan metabolites with
      herbicidal activity from Laceyella sacchari.

PMID- 24865862
TI  - Pyrenocines N-O: two novel pyrones from Colletotrichum sp. HCCB03289.

PMID- 24865863
TI  - AS2077715: a novel antifungal antibiotic produced by Capnodium sp. 339855.
AB  - A novel antifungal agent, AS2077715, was isolated from the fermentation broth of
      a fungal strain (339855) identified as a new Capnodium species based on
      morphological characteristics and large-subunit ribosomal DNA sequencing.
      AS2077715 was isolated as a white powder via solvent extraction, HP-20 and ODS-B
      column chromatography and crystallization, and was determined to have the
      molecular formula C25H41NO7. AS2077715 has a structure related to that of
      funiculosin, an inhibitor of mitochondrial cytochrome bc1 complex (complex III),
      and showed antifungal activity against Trichophyton species. 

PMID- 24865864
TI  - Therapeutic efficacy of AS2077715 against experimental tinea pedis in guinea pigs
      in comparison with terbinafine.
AB  - AS2077715 is a novel antifungal metabolite produced by the newly isolated fungal
      strain Capnodium sp. 339855. This compound has potent inhibitory activity against
      Trichophyton mentagrophytes mitochondrial cytochrome bc1 complex (complex III)
      and potent fungicidal activity against T. mentagrophytes, as measured in vitro.
      Here, we compared the effects of AS2077715 and terbinafine in a guinea pig model
      of tinea pedis. In a treatment regimen started from the day 7 after infection, 10
      daily oral doses of 10 and 20 mg kg(-1) AS2077715 and 20 mg kg(-1) of terbinafine
      significantly decreased fungal colony-forming units (CFUs) in foot pad skin. In a
      treatment regimen started from the day 11 after infection, 20 mg kg(-1) AS2077715
      significantly reduced fungal CFUs in foot pad skin after 7 daily doses in
      comparison with 20 mg kg(-1) terbinafine-treated guinea pigs. Our findings
      suggest that in vivo potency and efficacy of AS2077715 are equal to or greater
      than that of terbinafine, positioning AS2077715 as a good candidate for use in
      treating trichophytosis. 

PMID- 24865865
TI  - Influence of sub-inhibitory antibiotics and flow condition on Staphylococcus
      aureus ATCC 6538 biofilm development and biofilm growth rate: BioTimer assay as a
      study model.
AB  - Staphylococcus biofilm exhibits high antibiotic resistance and therapeutic doses
      of antibiotics are often sub-inhibitory. Whereas data are available on the effect
      of sub-inhibitory antibiotics on matrix formation, little is known on their
      influence on biofilm population. Here, using BioTimer Assay (BTA), a method
      developed to quantify biofilm population, the influence of sub-inhibitory
      gentamicin, ofloxacin and azithromycin on Staphylococcus aureus ATCC 6538 biofilm
      population in flow with respect to static condition was assessed. Antibiotics and
      flow condition increased biofilm population even if at different extent,
      depending on the antibiotic molecule. The greatest bacterial population was found
      in biofilm developed under flow condition in the presence of azithromycin. A
      significant increase in biofilm matrix was recorded for biofilm developed in the
      presence of antibiotics in flow with respect to static condition. The growth
      rates (GRs) of 24-h biofilm developed under the influence of antibiotics and flow
      condition were also evaluated using BTA and a specific mathematical model.
      Antibiotics and flow condition affected the GRs of 24-h biofilm even if at
      different extent. The lowest GR value was recorded for biofilm developed under
      flow condition in the presence of ofloxacin. Although further studies are needed,
      our data indicate that antibiotics and flow condition influenced biofilm
      development by increasing both bacterial population and matrix formation and
      affected the GRs of the developed biofilm. To the best of our knowledge, BTA is
      unique in allowing the calculation of the GRs of biofilm and it may be considered
      to be a useful study model to evaluate the activity of antibiofilm molecules. 

PMID- 24865866
TI  - AS2077715 is a selective inhibitor of fungal mitochondrial cytochrome bc1
      complex.
AB  - AS2077715 is a novel antifungal metabolite produced by the newly isolated fungal
      strain Capnodium sp. 339855. This compound has an analogous structure to
      funiculosin, an inhibitor of mitochondrial cytochrome bc1 complex (complex III).
      AS2077715 inhibited ubiquinol-cytochrome c reductase activity of Trichophyton
      mentagrophytes complex III with an IC50 of 0.9 ng ml(-1), while 6000-20,000 ng
      ml(-1) AS2077715 was required to obtain comparable inhibition of mammalian
      complex III. This inhibitor also suppressed the growth of T. mentagrophytes with
      a MIC of 0.08 MUg ml(-1), while cytotoxicity for mammalian cells was >6 MUg ml(
      1). These results indicate that AS2077715 is a selective inhibitor of fungal
      mitochondrial complex III. AS2077715 in doses of 1 MUg ml(-1) or greater showed
      fungicidal activity against T. mentagrophytes within 2 h of incubation. This
      early-onset effect of fungicidal activity was also exhibited by other complex III
      inhibitors. These results suggest that inhibition of complex III is a promising
      strategy for designing anti-Trichophyton agents and that AS2077715 can be a
      potential drug candidate for treating Trichophyton infections.

PMID- 24865867
TI  - Construction of a collagen-based, split-thickness cornea substitute.
AB  - Tissue-engineered corneas may become a promising alternative to allografts in the
      treatment of serious cornea defects because of the tunable characteristics of the
      biomaterials, biomimetic designs, and incorporation of patient's own cells. In
      this study, collagen foam was coated with a fibrous mat to mimic the stromal
      layer and the Bowman's layer. The stromal layer substitute was made of N-ethyl-N
      (3-dimethyl aminopropyl)carbodiimide/N-hydroxysuccinimide-cross-linked collagen
      chondroitin sulfate foam and seeded with primary human corneal keratocytes (HK).
      Retinal pigment epithelium (RPE) cells served as the epithelial layer after
      seeding on a dehydrothermally cross-linked collagen type I fibrous mat deposited
      directly on top of the foams by electrospinning. The physical characterization
      and the in vitro studies showed that the designed cornea replacement was suitable
      for cell attachment and growth, and co-culture of the two cell types induced more
      extracellular matrix (ECM) deposition than the single cell-seeded constructs. The
      fiber layer was shown to be successful in separating the HK and RPE cells, and
      still allowed them to maintain cell-cell communication as the increase in ECM
      deposition and the maintenance of the high transparency (~80%) suggested. This
      split-thickness corneal substitute was also shown to be readily suturable without
      any major tears at the end of a short co-culture of 30 days.

PMID- 24865869
TI  - Comparative efficacy of behavior therapy, cognitive therapy, and cognitive
      behavior therapy for chronic insomnia: a randomized controlled trial.
AB  - OBJECTIVE: To examine the unique contribution of behavior therapy (BT) and
      cognitive therapy (CT) relative to the full cognitive behavior therapy (CBT) for
      persistent insomnia. METHOD: Participants were 188 adults (117 women; M age =
      47.4 years, SD = 12.6) with persistent insomnia (average of 14.5 years duration).
      They were randomized to 8 weekly, individual sessions consisting of BT (n = 63),
      CT (n = 65), or CBT (n = 60). RESULTS: Full CBT was associated with greatest
      improvements, the improvements associated with BT were faster but not as
      sustained and the improvements associated with CT were slower and sustained. The
      proportion of treatment responders was significantly higher in the CBT (67.3%)
      and BT (67.4%) relative to CT (42.4%) groups at post treatment, while 6 months
      later CT made significant further gains (62.3%), BT had significant loss (44.4%),
      and CBT retained its initial response (67.6%). Remission rates followed a similar
      trajectory, with higher remission rates at post treatment in CBT (57.3%) relative
      to CT (30.8%), with BT falling in between (39.4%); CT made further gains from
      post treatment to follow up (30.9% to 51.6%). All 3 therapies produced
      improvements of daytime functioning at both post treatment and follow up, with
      few differential changes across groups. CONCLUSIONS: Full CBT is the treatment of
      choice. Both BT and CT are effective, with a more rapid effect for BT and a
      delayed action for CT. These different trajectories of changes provide unique
      insights into the process of behavior change via behavioral versus cognitive
      routes.

PMID- 24865870
TI  - The effects of written emotional disclosure and coping skills training in
      rheumatoid arthritis: a randomized clinical trial.
AB  - OBJECTIVE: Two psychological interventions for rheumatoid arthritis (RA) are
      cognitive-behavioral coping skills training (CST) and written emotional
      disclosure (WED). These approaches have developed independently, and their
      combination may be more effective than either one alone. Furthermore, most
      studies of each intervention have methodological limitations, and each needs
      further testing. METHOD: We randomized 264 adults with RA in a 2 * 2 factorial
      design to 1 of 2 writing conditions (WED vs. control writing) followed by 1 of 2
      training conditions (CST vs. arthritis education control training). Patient
      reported pain and functioning, blinded evaluations of disease activity and
      walking speed, and an inflammatory marker (C-reactive protein) were assessed at
      baseline and 1-, 4-, and 12-month follow-ups. RESULTS: Completion of each
      intervention was high (>90% of patients), and attrition was low (10.2% at 12
      month follow-up). Hierarchical linear modeling of treatment effects over the
      follow-up period, and analyses of covariance at each assessment point, revealed
      no interactions between writing and training; however, both interventions had
      main effects on outcomes, with small effect sizes. Compared with control
      training, CST decreased pain and psychological symptoms through 12 months. The
      effects of WED were mixed: Compared with control writing, WED reduced disease
      activity and physical disability at 1 month only, but WED had more pain than
      control writing on 1 of 2 measures at 4 and 12 months. CONCLUSIONS: The
      combination of WED and CST does not improve outcomes, perhaps because each
      intervention has unique effects at different time points. CST improves health
      status in RA and is recommended for patients, whereas WED has limited benefits
      and needs strengthening or better targeting to appropriate patients.

PMID- 24865871
TI  - A two-site randomized clinical trial of integrated psychosocial treatment for
      ADHD-inattentive type.
AB  - OBJECTIVE: This study evaluated the efficacy of the Child Life and Attention
      Skills (CLAS) program, a behavioral psychosocial treatment integrated across home
      and school, for youth with attention-deficit/hyperactivity disorder-inattentive
      type (ADHD-I). METHOD: In a 2-site randomized controlled trial, 199 children
      (ages 7-11 years) were randomized to CLAS (N = 74), parent-focused treatment
      (PFT, N = 74), or treatment as usual (TAU, N = 51). We compared groups on parent
      and teacher ratings of inattention symptoms, organizational skills, social
      skills, and global improvement at posttreatment and also at follow-up during the
      subsequent school year. RESULTS: CLAS resulted in greater improvements in teacher
      reported inattention, organizational skills, social skills, and global
      functioning relative to both PFT and TAU at posttreatment. Parents of children in
      CLAS reported greater improvement in organizational skills than PFT and greater
      improvements on all outcomes relative to TAU at posttreatment. Differences
      between CLAS and TAU were maintained at follow-up for most parent-reported
      measures but were not significant for teacher-reported outcomes. CONCLUSIONS:
      These findings extend support for CLAS across 2 study sites, revealing that
      integrating parent, teacher, and child treatment components, specifically adapted
      for ADHD-I, is superior to parent training alone and to usual care. Direct
      involvement of teachers and children in CLAS appears to amplify effects at school
      and home and underscores the importance of coordinating parent, teacher, and
      child treatment components for cross-setting effects on symptoms and impairment
      associated with ADHD-I.

PMID- 24865872
TI  - Gender and depression moderate response to brief motivational intervention for
      alcohol misuse among college students.
AB  - OBJECTIVE: Brief motivational interventions (BMIs) effectively reduce problematic
      drinking in college students. However, not all students benefit, and little is
      known about the subgroups of students for whom BMIs are most effective. In the
      present study, we examined 2 factors that may influence BMI efficacy: gender and
      depression. METHOD: We reanalyzed data from a clinical trial in which heavy
      drinking students (N = 330; 65% female) were randomized to a BMI (n = 165) or an
      assessment only control (n = 165). Depression was assessed at baseline; past
      month typical drinks per week, heavy drinking frequency, and consequences were
      assessed at baseline and 1 month. Three- and 2-way interactions among
      intervention condition (BMI vs. control), gender (male vs. female), and
      depression (low vs. high) were tested. RESULTS: We observed 3-way interaction
      effects on 2 outcomes: (a) typical drinks per week and (b) frequency of heavy
      drinking at 1 month. Relative to controls and adjusting for baseline drinking,
      low-depression women reduced their drinking more after a BMI whereas high
      depression women did not show differential improvement. In contrast, high
      depression men showed significant reductions in weekly drinks following the BMI
      whereas low-depression men did not show differential improvement. In addition,
      higher levels of depression were associated with higher levels of consequences at
      follow-up across conditions. CONCLUSIONS: BMIs are indicated for heavy drinking,
      depressed men, consistent with recommendations for implementing screening and
      brief intervention in mental health settings. However, BMIs may need to be
      refined to enhance their efficacy for depressed women.

PMID- 24865873
TI  - Erythema migrans-like lesions in the South require treatment given the current
      state of knowledge.

PMID- 24865874
TI  - ACR Appropriateness Criteria((r)) on renal failure.
AB  - Imaging plays a role in the management of patients with acute kidney injury or
      chronic kidney disease. However, clinical circumstances strongly impact the
      appropriateness of imaging use. In patients with newly detected renal
      dysfunction, ultrasonography can assess for reversible causes, assess renal size
      and echogenicity, and thus, establish the chronicity of disease. Urinary
      obstruction can be detected, but imaging is most useful in high-risk groups or in
      patients in whom there is a strong clinical suspicion for obstruction. Computed
      tomography, computed tomography or magnetic resonance arteriography, and
      percutaneous ultrasound-guided renal biopsy are valuable in other clinical
      situations. The American College of Radiology Appropriateness Criteria are
      evidence-based guidelines for specific clinical conditions that are reviewed
      every 3 years by a multidisciplinary expert panel. The guideline development and
      review include an extensive analysis of current medical literature from peer
      reviewed journals and the application of a well-established consensus methodology
      (modified Delphi) to rate the appropriateness of imaging and treatment procedures
      by the panel. In those instances where evidence is lacking or not definitive,
      expert opinion may be used to recommend imaging or treatment. 

PMID- 24865875
TI  - Measuring symptoms in gastrointestinal cancer: a systematic review of assessment
      instruments.
AB  - PURPOSE: It is critical for gastrointestinal cancer researchers and clinicians to
      have access to comprehensive, sensitive and simple-to-use symptom measures that
      allow them to understand and quantify the subjective patient experience.
      Development and validation of such scales requires training in psychometrics and
      occasionally uses technical jargon that can be difficult to penetrate. This
      review evaluates existing measures of gastrointestinal cancer symptoms, provides
      tool descriptions, and uses predefined, objective quality criteria to rate
      psychometric quality and facilitate tool choices for researchers and clinicians.
      METHODS: MEDLINE, EMBASE, CINAHL, and PsycINFO databases were systematically
      reviewed for scales assessing gastrointestinal cancer and gastrointestinal cancer
      site-specific symptoms. Evaluation criteria were the following: breadth of domain
      coverage (content validity), high internal consistency (alpha >=  .80),
      sensitivity to change, and extent of validation. RESULTS: In n = 36 validation
      studies, 26 gastrointestinal cancer symptom measures were identified. Of these, n
      = 13 tools met criteria for recommendation, and six in particular showed strong
      psychometric properties. The Functional Assessment of Cancer Therapy-Colorectal
      (FACT-C), European Organization for Research and Treatment of Cancer (EORTC)
      gastric cancer module (QLQ-STO22), FACT-Hepatobiliary (FACT-Hep), and EORTC
      oesophagus, oesophago-gastric junction and stomach module (QLQ OG-25) were
      identified as the most comprehensive and best validated scales for each of the
      major gastrointestinal cancer sites. The FACT-Colorectal Symptom Index (FCSI-9)
      and the National Comprehensive Cancer Network (NCCN) FACT-Hepatobiliary Symptom
      Index (FHSI-18) were specifically validated in patients with advanced colorectal
      and liver cancer and also demonstrated superior psychometric properties.
      CONCLUSIONS: Several comprehensive, well-validated scales exist to adequately
      assess gastrointestinal cancer site-specific symptoms. Specifically,
      gastrointestinal cancer submodules of the FACT quality of life questionnaire
      represent adequate tool choices in most instances and overall, were better
      validated than the respective EORTC tools. Further improvement of existing,
      highly rated measures is recommended.

PMID- 24865876
TI  - Which quality of life instruments are preferred by cancer patients in Japan?
      Comparison of the European Organization for Research and Treatment of Cancer
      Quality of Life Questionnaire-C30 and the Functional Assessment of Cancer Therapy
      General.
AB  - PURPOSE: We compared two health-related quality of life (HRQOL) instruments used
      for cancer patients [the European Organization for Research and Treatment of
      Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) and the Functional
      Assessment of Cancer Therapy-General (FACT-G)] to identify which instrument
      cancer patients most preferred. METHODS: Adult cancer patients who had received
      cancer treatments within the previous 2 years (n = 395) completed both surveys;
      participants assessed the importance, necessity, and appropriateness of each as
      an indicator of their quality of life. RESULTS: The patients significantly
      preferred the FACT-G over the EORTC QLQ-C30 as a more important (effect size (ES)
      = 0.37, P < 0.001), necessary (ES = 0.18, P < 0.001), and appropriate
      questionnaire (ES = 0.14, P = 0.005). The subgroups of patients with good
      performance status, and those who reported low levels of work disruption,
      significantly preferred the FACT-G more than the other. The corresponding
      correlation coefficients were the following: physical functioning and well-being
      subscale, r = 0.65; emotional functioning and well-being subscale, r = 0.60;
      social functioning and social/family well-being subscale, r = 0.00; and role
      functioning and functional well-being subscale, r = 0.41. CONCLUSIONS: We
      recommend using the FACT-G if the performance status of the subject is good,
      e.g., in outpatient or cancer survivor surveys, based on the observed patient
      preferences. When performance status is not good, an instrument should be chosen
      after considering the differences between their scale structures and social
      domains and based on the availability of disease-specific modules.

PMID- 24865877
TI  - Trajectory and predictors of quality of life during the dying process: roles of
      perceived sense of burden to others and posttraumatic growth.
AB  - PURPOSE: Quality of life (QOL) at end of life (EOL) is related to important
      themes, e.g., "sense of burden to others" and "perceived posttraumatic growth,"
      which have never been investigated concurrently. The purposes of this study were:
      (1) to describe the trajectory of QOL during the dying process and (2) to
      identify determinants of QOL, including the roles of perceived sense of burden to
      others and posttraumatic growth. METHODS: A convenience sample of 313 terminally
      ill cancer patients was surveyed and longitudinally followed until death. QOL was
      measured by a modified McGill quality of life scale, and determinants were
      evaluated by a multiple linear regression model with the generalized estimating
      equation. RESULTS: Terminally ill Taiwanese cancer patients' QOL decreased
      substantially as their death approached. However, after controlling for
      confounders, patients' QOL did not change significantly in the last months of
      their life. QOL was significantly better for female and non-middle-aged patients
      with a religious affiliation of Buddhism/Taoism. Poorer QOL tended to be
      experienced by patients with greater physical symptom distress, anxiety, and
      depression. Patient QOL increased with greater tangible support, but decreased
      with greater emotional and affectionate social support. QOL was diminished by a
      greater degree of perceived burden to others but improved with greater perceived
      posttraumatic growth. CONCLUSIONS: Deteriorating QOL as death approaches may not
      be inevitable. Optimal QOL at EOL may be achieved by interventions designed to
      adequately manage physical and psychological symptoms, enhance social support,
      lighten perceived sense of burden to others, and facilitate experiences of
      posttraumatic growth.

PMID- 24865878
TI  - Neurobehavioural changes in patients following brain tumour: patients and
      relatives perspective.
AB  - PURPOSE: Patients and relatives experiences of behavioural and personality
      changes following brain tumour were assessed to determine whether these changes
      are more prominent in the experience of patients with frontal tumours and their
      relatives as a first step to evaluate the need to develop appropriate support and
      management of such changes, which have a substantial impact on social
      functioning, and ultimately to improve quality of life. METHODS: Patients and
      relatives rated the patients' current levels of apathy, disinhibition and
      executive dysfunction on the Frontal Systems Behaviour Scale. Patients also
      completed the Hospital Anxiety and Depression Scale. The data from 28 patients
      with frontal tumours and 24 of their relatives, and 27 patients with nonfrontal
      tumours and 25 of their relatives, were analysed. RESULTS: Patients with frontal
      tumours rated themselves significantly higher than patients with nonfrontal
      tumours on all frontal systems-related behaviours. The number of patients
      reporting clinical levels of difficulty was significantly greater in patients
      with frontal tumours for disinhibition. The ratings of relatives of patients with
      frontal tumours were significantly higher than those of relatives of patients
      with nonfrontal tumours for apathy. Clinically significant levels of apathy and
      executive dysfunction were however reported by at least 40 % of patients and
      relatives regardless of tumour location. Clinical levels of anxiety were reported
      by significantly more patients with frontal tumours than those with nonfrontal
      tumours. CONCLUSION: Support and management of behavioural and personality change
      for patients with brain tumours and their relatives, regardless of tumour
      location, would be most appropriate.

PMID- 24865879
TI  - Antioxidant, antibacterial, and antibiofilm properties of polyphenols from
      muscadine grape (Vitis rotundifolia Michx.) pomace against selected foodborne
      pathogens.
AB  - Polyphenols are predominantly secondary metabolites in muscadine grapes, playing
      an important role in the species' strong resistance to pests and diseases. This
      study examined the above property by evaluating the antioxidant, antibacterial,
      and antibiofilm activities of muscadine polyphenols against selected foodborne
      pathogens. Results showed that antioxidant activity for different polyphenols
      varied greatly, ranging from 5 to 11.1 mmol Trolox/g. Antioxidant and
      antibacterial activities for polyphenols showed a positive correlation. Muscadine
      polyphenols exhibited a broad spectrum of antibacterial activity against tested
      foodborne pathogens, especially Staphylococcus aureus (MIC = 67-152 mg/L).
      Muscadine polyphenols at 4 * MIC caused nearly a 5 log10 CFU/mL drop in cell
      viability for S. aureus in 6 h with lysis, whereas at 0.5 * MIC they inhibited
      its biofilm formation and at 16 * MIC they eradicated biofilms. Muscadine
      polyphenols showed synergy with antibiotics and maximally caused a 6.2 log10
      CFU/mL drop in cell viability at subinhibitory concentration. 

PMID- 24865880
TI  - Effects of an intensive hog farming operation on groundwater in east
      Mediterranean (I): a study on electrical conductivity, as well as nitrogen and
      sulfur nutrients.
AB  - The discharge of treated animal wastewater produced in concentrated animal
      feeding operations (CAFOs) on surface soil (within CAFOs borders) leads to
      groundwater degradation. In this research, groundwater degradation effects of an
      intensive hog farming operation, located in a Mediterranean area, were
      investigated. Treated animal wastewater was discharged on a small plot (~10.8 ha)
      with a geologic fault. Groundwater samples were taken from seven groundwater
      monitoring wells close to the farm. These wells were affected by the subsurface
      flow of waters, due to the presence of the geologic fault. In the summer, a
      significant increase of electrical conductivity values was noted in and
      attributed to falling water table levels. During the winter, significant
      increases in concentrations of ammonium nitrogen, nitrate nitrogen, and sulfate
      were noted and attributed to high precipitation, which assisted in the leaching
      of nitrogen and sulfur to groundwater.

PMID- 24865882
TI  - Frequency function in atomic force microscopy applied to a liquid environment.
AB  - Scanning specimens in liquids using commercial atomic force microscopy (AFM) is
      very time-consuming due to the necessary try-and-error iteration for determining
      appropriate triggering frequencies and probes. In addition, the iteration easily
      contaminates the AFM tip and damages the samples, which consumes probes. One
      reason for this could be inaccuracy in the resonant frequency in the feedback
      system setup. This paper proposes a frequency function which varies with the tip
      sample separation, and it helps to improve the frequency shift in the current
      feedback system of commercial AFMs. The frequency function is a closed-form
      equation, which allows for easy calculation, as confirmed by experimental data.
      It comprises three physical effects: the quasi-static equilibrium condition, the
      atomic forces gradient effect, and hydrodynamic load effect. While each of these
      has previously been developed in separate studies, this is the first time their
      combination has been used to represent the complete frequency phenomenon. To
      avoid "jump to contact" issues, experiments often use probes with relatively
      stiffer cantilevers, which inevitably reduce the force sensitivity in sensing low
      atomic forces. The proposed frequency function can also predict jump to contact
      behavior and, thus, the probe sensitivity could be increased and soft probes
      could be widely used. Additionally, various tip height behaviors coupling with
      the atomic forces gradient and hydrodynamic effects are discussed in the context
      of carbon nanotube probes. 

PMID- 24865883
TI  - Object tracking using adaptive covariance descriptor and clustering-based model
      updating for visual surveillance.
AB  - We propose a novel approach for tracking an arbitrary object in video sequences
      for visual surveillance. The first contribution of this work is an automatic
      feature extraction method that is able to extract compact discriminative features
      from a feature pool before computing the region covariance descriptor. As the
      feature extraction method is adaptive to a specific object of interest, we refer
      to the region covariance descriptor computed using the extracted features as the
      adaptive covariance descriptor. The second contribution is to propose a weakly
      supervised method for updating the object appearance model during tracking. The
      method performs a mean-shift clustering procedure among the tracking result
      samples accumulated during a period of time and selects a group of reliable
      samples for updating the object appearance model. As such, the object appearance
      model is kept up-to-date and is prevented from contamination even in case of
      tracking mistakes. We conducted comparing experiments on real-world video
      sequences, which confirmed the effectiveness of the proposed approaches. The
      tracking system that integrates the adaptive covariance descriptor and the
      clustering-based model updating method accomplished stable object tracking on
      challenging video sequences. 

PMID- 24865884
TI  - Multi-agent cooperative target search.
AB  - This paper addresses a vision-based cooperative search for multiple mobile ground
      targets by a group of unmanned aerial vehicles (UAVs) with limited sensing and
      communication capabilities. The airborne camera on each UAV has a limited field
      of view and its target discriminability varies as a function of altitude. First,
      by dividing the whole surveillance region into cells, a probability map can be
      formed for each UAV indicating the probability of target existence within each
      cell. Then, we propose a distributed probability map updating model which
      includes the fusion of measurement information, information sharing among
      neighboring agents, information decay and transmission due to environmental
      changes such as the target movement. Furthermore, we formulate the target search
      problem as a multi-agent cooperative coverage control problem by optimizing the
      collective coverage area and the detection performance. The proposed map updating
      model and the cooperative control scheme are distributed, i.e., assuming that
      each agent only communicates with its neighbors within its communication range.
      Finally, the effectiveness of the proposed algorithms is illustrated by
      simulation. 

PMID- 24865885
TI  - Characterizing physicians' information needs at the point of care.
AB  - Physicians have many information needs that arise at the point of care yet go
      unmet for a variety of reasons, including uncertainty about which information
      resources to select. In this study, we aimed to identify the various types of
      physician information needs and how these needs relate to physicians' use of the
      database PubMed and the evidence summary tool UpToDate. We conducted semi
      structured interviews with physicians (Stanford University, United States; n =
      13; and University Medical Center Utrecht, the Netherlands; n = 9), eliciting
      participants' descriptions of their information needs and related use of PubMed
      and/or UpToDate. Using thematic analysis, we identified six information needs:
      refreshing, confirming, logistics, teaching, idea generating and personal
      learning. Participants from both institutions similarly described their
      information needs and selection of resources. The identification of these six
      information needs and their relation to PubMed and UpToDate expands upon
      previously identified physician information needs and may be useful to medical
      educators designing evidence-based practice training for physicians. 

PMID- 24865886
TI  - Help wanted: developing clinician leaders.
AB  - Because healthcare faces challenges, such as ensuring quality and access and
      controlling cost, effective leadership is needed at every level of healthcare
      organizations. Yet, physicians are trained in clinical and scientific skills but
      not in leadership competencies. Furthermore, clinicians often feel ill-prepared
      to assume managerial and leadership roles. To close this gap, training in
      leadership competencies, such as emotional intelligence, communication, teamwork,
      and change management, is urgently needed for physicians and clinicians of all
      disciplines. Leadership training should be multidisciplinary and should begin
      early in clinicians' careers. 

PMID- 24865887
TI  - Improving communication skills in the Southeast Asian health care context.
AB  - The aim of these two PhD thesis are to develop a guideline on doctor-patient
      communication skills based on cultural characteristics of Southeast Asian context
      and to develop communication skills training for nurses to enhance their
      contribution to the informed consent and shared decision making process, in the
      same context. These studies started with qualitative methods; including grounded
      theory methodology, by exploring doctors', patients', medical students' and
      nurses' perceptions on the current and desired communication skills in which
      influenced by culture. Based on the results, we design communication skills
      training and evaluate the training with quantitative methods, using pre and post
      test studies. Southeast Asian desired ideal partnership style in communicating
      with their doctors. More emphasize on basic skills such as listening to subtle
      non-verbal cues are needed for doctors and nurses. A guideline on doctor-patient
      communication tailored to local culture was developed as well as training for
      nurses using 4CID design to enhance their contribution to the shared decision
      making process. To promote two-way interaction between doctors and patients and
      between health professionals require mastering basic skills in communicating with
      people, such as explorations on the unspoken concern. In a culturally
      hierarchical context of Indonesia, this two-way interaction is quite a challenge.
      To generalize our studies to other culture, more studies with rigorous methods
      should follow. To promote the use of basic skills in communicating with patients
      to approach the desired partnership communication style in Southeast Asian
      context, we need to use local evidences. 

PMID- 24865888
TI  - Podcasting as a novel way to communicate with medical school applicants.
AB  - Podcasting in medical education is becoming more widely used and may be a useful
      tool for communicating with applicants to medical school. Given recent trends in
      the popularity of podcasting and mobile media, we created a podcast to
      communicate more effectively with applicants to our medical school as well as
      with the broader premedical community. The purpose of this study was to
      characterize the listening habits and motivations of our audience and compare the
      podcast's benefits to those of other resources. We additionally sought to
      understand patterns by which our podcast was consumed by a premedical audience.
      We surveyed medical school applicants who interviewed at the University of
      Chicago Pritzker School of Medicine for matriculation in 2013. Forty-one percent
      of those surveyed had listened to the podcast prior to their interview. Only 12 %
      of listeners accessed the podcast using a mobile device. Ninety-two percent of
      listeners felt that it faithfully represented the medical school, and 81 % felt
      that listening would encourage the decision to matriculate. A majority of
      listeners responded that the podcast was more helpful than other traditional
      resources. This is the first use of podcasting in medical school admissions and
      represents a novel way to communicate with prospective students. Our findings
      demonstrate that podcasting can be an effective tool for communicating with
      applicants to medical school and highlight its usefulness in recruitment. This
      method of communication could be adopted by other medical schools to enhance the
      ways in which they inform their own prospective medical students. 

PMID- 24865889
TI  - Musculoskeletal education: an assessment of the clinical confidence of medical
      students.
AB  - Musculoskeletal (MSK) conditions account for nearly 15-30 % of encounters in a
      primary care practice. Yet, studies demonstrate that medical students and
      residents lack the knowledge and confidence to care for many MSK conditions. This
      study addresses the design of focused MSK educational practices towards improving
      students' knowledge, interest, and confidence for conducting MSK examinations.
      Students attending a voluntary educational symposium on sports medicine were
      recruited to participate. The symposium was directed toward teaching elements of
      the MSK exam. Participants completed validated pre- and post-workshop surveys
      that assessed confidence in performing MSK examinations as well as satisfaction
      and perceived importance of MSK education. Additionally, mean survey responses
      from a convenience group of students who did not participate in the symposium
      were compared against the intervention group. Thirteen students participated in
      the educational symposium. Hundred and nine students completed the general
      survey. In the non-intervention group, students demonstrated knowledge and
      confidence improvements through the second year of medical school but did not
      show similar improvement in subsequent years. No difference in MSK confidence
      scores between fourth-year students going into high versus low MSK focused
      specialities was observed. In the intervention group students demonstrated
      improvements in confidence with respect to the knee, shoulder and ankle exams (p
      < 0.01). Areas not covered such as concussions and neuromuscular impairments
      failed to show significant change. Current core clinical training, at least at
      our school, does not achieve satisfactory levels of knowledge and confidence with
      respect to caring for MSK conditions. However, a focused didactic and skill
      development intervention does produce significant improvements. Follow-up is
      needed to determine whether these improvements are sustained. 

PMID- 24865890
TI  - Percutaneous epicardial ablation in ventricular arrhythmias.
AB  - INTRODUCTION: Reentrant circuits of ventricular tachycardia may involve not only
      the endocardium but also the epicardium. Epicardial ablation can be useful in
      these situations. OBJECTIVE: The aim of this study was to assess efficacy, safety
      and complications in a series of consecutive patients who underwent ablation of
      ventricular tachycardia with epicardial mapping. METHODS: The study included all
      patients undergoing ventricular tachycardia ablation with epicardial mapping from
      2004 to 2012. Of a total of 95 ablations, an epicardial approach was attempted in
      nine patients, eight male, mean age 58+/-12 years. Endocardial mapping was
      performed in all patients previously or simultaneously. The etiology of the
      arrhythmia was non-ischemic in eight patients and ischemic in one. We compared
      the number of events in the six months prior to the epicardial procedure and six
      months after. RESULTS: Percutaneous epicardial access was achieved in eight
      patients. In one case it was not possible due to the presence of adhesions. In
      none of the patients was the procedure repeated and there were no major
      complications during hospitalization. In a mean follow-up of 3.5+/-1.2 years, one
      patient suffered stroke; there were no other medium-to-long-term complications
      and the number of ventricular tachycardia episodes was reduced in all patients
      after ablation. CONCLUSIONS: Epicardial radiofrequency ablation of ventricular
      tachycardia was effective in reducing morbidity in eight patients, with a low
      risk of complications in the short and medium-to-long term.

PMID- 24865891
TI  - Uranium(VI) remediation from aqueous environment using impregnated cellulose
      beads.
AB  - Use of cellulose based adsorbents for post treatment of contaminated water
      provides significant removal and recovery of trace quantities of radioactive and
      highly toxic U(VI) ions. Efficiency of the adsorbent was enhanced by impregnation
      of nano Fe2O3. Variables considered for obtaining optimized process conditions
      were solution pH, adsorbent dosage, initial metal ion concentration, additive
      content and contact time. The batch adsorption study revealed highly pH dependent
      adsorption with 100% adsorption efficiency at pH 7 using 1.5 g of adsorbent
      impregnated with 6 wt% Fe2O3 for 50 mL solution capacity in 150 min. The
      adsorption capacity was noted to be 7.6 mg/g. The adsorption mechanism was
      studied at pH 7 maintained using dilute ammonia solution to prevent the effect of
      any interfering cation. Uptake of U(VI) was found to be predominately via an
      intraparticle diffusion mechanism following pseudo second-order kinetic model,
      which is clearly reflected from the non-spontaneous thermodynamics yielding a
      positive free energy value. Recovery of the adsorbed U(VI) ions was highly
      feasible using 0.05 N HNO3 and the regeneration of the adsorbent using 0.01 N
      NaOH. 

PMID- 24865897
TI  - Population genetics of Thamnaconus hypargyreus (Tetraodontiformes: Monacanthidae)
      in the South China Sea.
AB  - Knowledge of population structure is particularly important for long-term
      fisheries management and conservation. Lesser-spotted leatherjacket Thamnaconus
      hypargyreus is an economically important fish species in the South China Sea.
      Fish specimens (totally 158 individuals) used in this study were collected from
      five geographical locations in the north of the South China Sea and the
      southwestern Nansha Islands. The results were as follows: a total of 636
      nucleotides of the mitochondrial DNA (mtDNA) control region (CR) of T.
      hypargyreus were amplified by polymerase chain reaction (PCR) technology. Both
      103 mutations of nucleotide acids without inserting or deleting one and 91
      haplotypes were found among the examined CR fragment. High haplotype diversity
      (0.9419 +/- 0.0151) and nucleotide diversity (0.0095 +/- 0.00506) relatively
      together with a recent and sudden population expansion which characterizes the
      genetic population structure of this species. Analysis of molecular variance
      (AMOVA) and the fixation indices (Fst) of five groups showed that the genetic
      variance mainly came from individuals within groups, and there was no genetic
      differentiation between groups. The phylogenetic trees including maximum
      likelihood (ML) and Bayesian inference (BI) proved no phylogeographic
      differentiation structure in five groups. The mtDNA marker suggested the five
      groups should be genetic homogeneity, which implied T. hypargyreus in the north
      and southwest continental shelf of the South China Sea belongs to one population.

PMID- 24865898
TI  - Complete F-type mitochondrial genome of freshwater mussel Lanceolaria glayana.
AB  - Lanceolaria glayana is widely distributed in China as a common species of
      freshwater pearl mussel. The complete F-type mitochondrial genome of L. glayana
      was firstly reported by this research. This circle genome (15,736 bp in size)
      contains 13 protein-coding genes, 22 tRNA genes, 2rRNA genes. Most of the protein
      coding genes initiated with the orthodox ATG start codon while COI and ND4 were
      corresponding to ATA start codon. Further, 28 non-coding regions were found
      throughout the mitogenome of L. glayana, ranging from 1 to 310 bp. The maximum is
      between ND5 and tRNA Gln (310 bp), which is longer than the control region
      sequences (about 280 bp) of freshwater mussels from Poland and South Korea. 

PMID- 24865899
TI  - The complete mitochondrial genome of Capricornis sp., possible a new species of
      Serow from Guizhou, China.
AB  - The genus Capricornis was widely distributed in Asia. In the present study, the
      complete mitochondrial genome of Capricornis sp., possible a new species of Serow
      from Guizhou province of China, was sequenced for the first time. Sequence
      analysis showed it is 16,441 bp in length, consisting of 12S rRNA gene, 16S rRNA
      gene, 22 transfer RNA (tRNA) genes, 13 protein-coding genes and one control
      region (CR). 

PMID- 24865900
TI  - The complete mitochondrial genome of the Jingxi duck (Anas platyrhynchos).
AB  - The entire mitochondrial genome of Jingxi duck from China was 16,603 bp in
      length, and has been analyzed for gene locations, length, start codons and stop
      codons. With the base composition of 29.20% for A, 22.19% for T, 32.82% for C,
      15.79% for G, so the percentage of A and T (51.39%) was slightly higher than
      those of G and C. The Jingxi duck mitochondrial genome contained two ribosomal
      RNA genes, 13 protein-coding genes, 22 transfer RNA genes and one non-coding
      control region (D-loop region). The arrangement of these genes was the same as
      most birds. The complete mitochondrial genome sequence of the Jingxi duck will be
      useful for phylogenetics, and provide an important data set for further study on
      the germplasm resources.

PMID- 24865892
TI  - Theoretical model of critical issues in informed consent in HIV vaccine trials.
AB  - The informed consent process (ICP) for HIV vaccine trials poses unique challenges
      and would benefit from improvements to its historically based structure and
      format. Here, we propose a theoretical framework that provides a basis for
      systematically evaluating and addressing these challenges. The proposed framework
      follows a linear pathway, starting with the precondition of voluntariness, three
      main variables of valid decision-making (competency, provision of information and
      understanding) and then the consequential outcome of either refusal or consent to
      participate. The existing literature reveals that culturally appropriate
      provision of information and resultant understanding by the vaccine trial
      participant are among the most significant factors influencing the authenticity
      of valid decision-making, though they may be overridden by other considerations,
      such as individual altruism, mistrust, and HIV-related stigma. Community
      collaborations to foster bidirectional transmission of information and more
      culturally tailored consenting materials, therefore, represent a key opportunity
      to enhance the ICP. By providing a visual synopsis of the issues most critical to
      IC effectiveness in a categorical and relational manner, the framework provided
      here presents HIV vaccine researchers a tool by which the ICP can be more
      systematically evaluated and consequently improved. 

PMID- 24865901
TI  - The complete mitochondrial genome of the Byasa alcinous (Lepidoptera:
      Papilionidae: Papilioninae).
AB  - The complete mitochondrial genome (mitogenome) of Byasa alcinous (Lepidoptera:
      Papilionidae: Papilioninae) is a circular molecule of 15,266 bp in length,
      containing 37 typical insect mitochondrial genes: 13 protein coding genes (PCGs),
      2 rRNA genes, 22 tRNA genes and a non-coding AT-rich region. Its gene order and
      arrangement are identical to all other available butterfly mitogenomes. All PCGs
      start with a typical ATN initiation codon, except for COI, which is initiated by
      the CGA codon as observed in other butterfly species. Ten PCGs terminate in the
      complete stop codon TAA or TAG, whereas the COI, COII and ND4 genes end with
      single T. Ten intergenic spacers (73 bp in total), and 12 overlapping regions (28
      bp in total) are dispersed throughout the whole genome. The non-coding AT-rich
      region is 405 bp long and contains some conserved structures similar to those
      found in other butterfly mitogenomes, such as the motif ATAGA followed by a 12-bp
      poly-T stretch and a microsatellite-like (AT)14 element preceded by the ATTTA
      motif. Additionally, a 11-bp poly-T sequences and a microsatellite-like (AT)7
      repeated elements are detected in this region. 

PMID- 24865902
TI  - Complete mitochondrial genome of Aphis gossypii Glover (Hemiptera: Aphididae).
AB  - The complete mitochondrial genome of the cotton-melon aphid, Aphis gossypii
      Glover, was sequenced using a combination of high-throughput sequencing,
      traditional PCR amplification, and Sanger sequencing. The genome is 15,869 bp in
      length, and contains 37 typical coding genes, one non-coding AT-rich region, and
      a repeat region found exclusively in aphids. The base composition of the genome
      is A (45.4%), T (38.3%), C (10.4%), and G (5.9%). All protein coding genes start
      with a typical ATN initiation codon; all genes use the standard termination codon
      (TAA) except ND4 that ends with a single TA. 

PMID- 24865903
TI  - Rearrangement of trnQ-trnM in the mitochondrial genome of Allantus luctifer
      (Smith) (Hymenoptera: Tenthredinidae).
AB  - The complete mitochondrial genome of the Allantus luctifer (Smith) (Hymenoptera:
      Tenthredinidae: Allantinae) is reported in this study (GenBank accession No.
      KJ713152). This is the first mitochondrial genome from the subfamily Allantinae
      and the first completely sequenced mitochondrial genome from the Tenthredinoidea.
      The length of this mitochondrial genome is 15,418 bp with an A+T content of
      81.13%, including 13 protein-coding, 2 rRNA and 22 tRNA gene, and an A+T-rich
      region (Table 1). Gene arrangement is identical to the other two mitochondrial
      genomes of tenthredinoid species in nearly all region as in the pupative
      ancestral arrangement of insects. The ancestral pattern of "A+T-rich region
      trnI(+)-trnQ(-)-trnM(+)" was rearranged to "trnM(-)-trnQ(+)-A+T-rich region
      trnI(+)", which is novel to the Hymenoptera. All protein-coding genes start with
      ATN start codon. Eleven protein-coding genes stop with termination codon TAA,
      whereas one protein-coding gene uses incomplete stop codon TA and one uses T. The
      A+T-region is 463 bp long with an A+T content of 86.6%. 

PMID- 24865904
TI  - First complete mitochondrial genome of primitive crab Homologenus malayensis
      (Decapoda: Brachyura: Podotremata: Homolidae).
AB  - The taxonomy and phylogeny of brachyuran crabs, and particularly of the
      Podotremata, have been the subjects of controversy due to their morphological
      diversity and complexity. The first complete mitochondrial genome (mitogenome)
      sequence of primitive crab Homologenus malayensis has been determined. The
      mitogenome is 15,793 bp in length, with A + T content 71.7%. The gene content and
      order are consistent with those in typical brachyuran crabs. A putative control
      region of 883 bp is identified due to its position (between srRNA and tRNA(Ile))
      and AT richness (75.5%). Notably, the control region in H. malayensis contains
      nine identical specific repeat units of 42 bp and 11 identical repeat units of 2
      bp with a total length of 400 bp, which is different from other crabs. These
      results are expected to provide useful information on both genomics and the
      future phylogenetic study of primitive crabs. 

PMID- 24865905
TI  - The complete mitochondrial genome of Pseudogyrinocheilus prochilus
      (Cypriniformes: Cyprinidae).
AB  - The complete mitochondrial sequence of Pseudogyrinocheilus prochilus, an endemic
      species to China and mainly distributed in upper Yangtze River and its
      tributaries, was obtained by PCR. It was 16,595 bp in length and comprised 37
      mitochondrial genes (22 transfer RNA genes, 13 protein-coding genes, 2 ribosomal
      RNA genes) and 2 non-coding regions. The overall base composition of H-strand was
      31.40% A, 26.78% C, 16.18% G, and 25.64% T. Most of the genes are encoded on
      heavy strand, except for eight tRNA and ND6 genes. The composition and order of
      mitochondrial gene have no unique characteristics compared to most of other
      fishes.

PMID- 24865907
TI  - The complete mitochondrial genome of Aplysia kurodai (Anaspidea: Aplysiidae).
AB  - Complete mitochondrial genome is sequenced from an opisthobranch gastropod
      Aplysia kurodai. Mitochondrial genome size of the species is 14,113 bp. The
      mitochondrial genome of A. kurodai contains 13 protein coding genes, two
      ribosomal RNA genes, and 22 tRNA genes like mitochondrial genomes of congeneric
      species. The gene order of protein coding genes is identical to that of other
      Aplysia species. A+T content (65.9%) of the mitochondrial genome is included in
      the range for A+T content of congeneric species. This genome data provides
      evolutionary and systematic implications for the related species. 

PMID- 24865906
TI  - The complete mitochondrial genome of Rasbora borapetensis (Cypriniformes:
      Cyprinidae: Rasbora).
AB  - The traditional polymerase chain reaction method was employed to obtain the
      complete mitochondrial genome of Rasbora borapetensis. The mitogenome was
      determined to be a 16,510 bp long circular molecule. It contained the typical
      complement of 13 protein-coding genes, 2 rRNAs and 22 tRNAs. This is first report
      on the complete mitogenome sequence of R. borapetensis. 

PMID- 24865908
TI  - Population phylogenomic analysis and origin of mitochondrial DNA in Chinese
      domestic pig.
AB  - The genetic diversity of eight domestic pigs was analyzed using a hypervariable
      fragment in the mitochondrial (mt) DNA control region; a portion of the
      hypervariable control region (515 bp) was sequenced from 153 samples. Haplotype
      diversity and nucleotide diversity in Yushan black pig populations were
      significantly higher than other populations (p < 0.01). A neighbor-joining tree
      was constructed from domestic pig mtDNA and five wild pigs. The results indicate
      that there are only small differences among individual pigs from different
      regions. Networks of the domestic pigs were constructed to better visualize the
      relationships between sequences. Each core haplotype was surrounded by a star
      like pattern, consistent with recent population expansion.

PMID- 24865909
TI  - Complete mitochondrial genome sequence of golden pompano Trachinotus ovatus.
AB  - The complete mitochondrial genome of Trachinotus ovatus was determined by the
      polymerase chain reaction (PCR). The mitogenome is 16,564 bp long and has the
      typical vertebrate mitochondrial gene arrangement, including 13 protein-coding
      genes, 22 tRNA genes, 2 rRNA genes and one control region. The overall base
      composition of mitogenome is estimated to be 29.0% for A, 28.9% for C, 26.2% for
      T, 15.9% for G, respectively, with a high A + T content (55.2%). With the
      exception of ND6 and eight tRNA genes, all other mitochondrial genes are encoded
      on the heavy strand. The control region contains a dinucleotide repeat motif,
      (AT)5. This mitogenome sequence would play an important role in population
      genetics and the molecular taxonomy of T. ovatus. 

PMID- 24865910
TI  - Mitochondrial genome of the Salanx cuvieri (Osteichthyes: Salangidae).
AB  - Salanx cuvieri, a salangid species endemic to China, is mainly distributed in the
      coastal waters in South China. In this study, we have studied the complete
      mitochondrial genome of the S. cuvieri. The results show that the complete mtDNA
      of S. cuvieri is 16,588 bp in length, which contains 13 protein-coding genes, 22
      tRNA genes, 2 rRNA genes (12S rRNA and 16S rRNA), and 1 control region (CR). The
      base composition of the genome is 25.3% A, 24% T, 18.2% G, and 32.1% C. Most of
      the genes are existed in the H-strand, except for the ND6 and other 9 tRNA genes
      which are encoded on L-strand. A recent study on S. cuvieri has revealed that
      significant genetic differentiations are found among populations inhabiting
      different estuaries, so our result can contribute to the preservation of this
      endangered species. 

PMID- 24865911
TI  - Complete mitochondrial genome of the blacktip reef shark Carcharhinus
      melanopterus (Carcharhiniformes: Carcharhinidae).
AB  - The complete mitochondrial genome of the blacktip reef shark Carcharhinus
      melanopterus is determined for the first time in this study. The gene composition
      and order in the mitogenome of C. melanopterus is identical to most vertebrates.
      The overall base composition is 31.3% A, 25.3% C, 13.3% G and 30.1% T. There are
      29 bp overlaps and 21 bp short intergenic spaces in the mitogenome. Two start
      codons and three stop codons were found in protein-coding genes. The
      dihydrouridine arm of tRNA-Ser2 was replaced by a simple loop and the other tRNAs
      could be folded into the typical cloverleaf structure. The termination associated
      sequence (TAS) and the conserved sequence blocks (CSB1-3) are found in the
      control region. 

PMID- 24865912
TI  - The complete mitochondrial genome of Tanakia lanceolata (Cypriniformes:
      Cyprinidae).
AB  - Bitterling Tanakia lanceolata is a small sized freshwater fish species. The
      unique reproductive behavior makes bitterlings monophyletic. In this study, the
      complete mitochondrial genome of T. lanceolata is sequenced to be 16,607 bp in
      length, including 13 protein-coding genes, 2 ribosomal RNAs, 22 transfer RNAs, a
      control region and the origin of the light strand replication. The overall base
      composition of T. lanceolata in descending order is A 28.3%, C 28.0%, T 26.1%,
      and G 17.6%, with a slight A + T bias. The mitogenome sequence data may provide
      useful information to the population genetics analysis of T. lanceolata and the
      elucidation of evolutionary mechanisms in Cyprinidae. 

PMID- 24865913
TI  - The complete mitochondrial gemone of Phoxinus lagowskii (Teleostei,
      Cypriniformes: Cyprinidae).
AB  - In this paper, we determined the whole mitochondrial DNA (mtDNA) sequence of
      Phoxinus lagowskii, a small freshwater fish that is distributed in rivers of
      north China, Russia and North Korea. The entire sequence of P. lagowskii
      mitochondrial genome is 16,699 bp in size, consisting of 13 protein-coding genes,
      2 ribosomal RNA genes (12S rRNA and 16S rRNA), 22 transfer RNA genes (tRNA) and 1
      putative control region. Most of the genes are encoded on the heavy strand except
      ND6 and eight tRNA genes (Gln, Ala, Asn, Cys, Try, Ser, Glu and Pro) encoded on
      the light strand. 

PMID- 24865914
TI  - Complete sequence and gene organization of the mitochondrial genome of Podocnemis
      unifilis (Pleurodira: Podocnemididae).
AB  - The mitochondrial genome of Podocnemis unifilis (Pleurodira: Podocnemididae) is
      16,493 bp in length, which contains 13 protein-coding genes, 2 ribosomal RNAs, 22
      transfer RNAs, and a control region. The A+T content of the overall base
      composition of H-strand is 61.7% (T: 27.7%, C: 25.5%, A: 34.0%, G: 12.8%). ATP6,
      ATP8, CO3, ND4-6 and Cyt b genes begin with ATG as start codon, ND1, ND2 and ND4L
      begin with ATT, CO1 starts with GTG, CO2 starts with ATA, ND3 starts with ATC.
      ATP6, CO2, ND4L and ND5 genes are terminated with TAA as stop codon, ND1, ND2,
      ND3, ND6 and CO1 end with TAG, and the other four protein-coding genes end with
      an incomplete stop codon (a single stop nucleotide T or TA). A long unit repeat
      region is found in the control region. 

PMID- 24865915
TI  - Mitochondrial genome of Japanese angel shark Squatina japonica (Chondrichthyes:
      Squatinidae).
AB  - Squatina japonica belonging to the monogenetic family Squatinidae is endemic to
      the Northwest Pacific. The complete mitochondrial genome sequence of S. japonica
      is 16,689 bp long and comprises 13 protein-coding genes, 22 tRNA genes, 2 rRNA
      genes, and 1 control region. The base composition of the genome is 31.10% A,
      31.04% T, 24.42% C, and 13.43% G. The geographic clade and phylogenetic
      relationship of S. japonica are ambiguous. Therefore, studying the complete
      mitochondrial genome of S. japonica is highly important to understand the
      aforementioned aspect and to analyze the conservation genetics in the genus
      Squatina. 

PMID- 24865916
TI  - The complete mitochondrial genome of Schizothorax chongi (Fang, 1936) (Teleostei,
      Cyprinidae, Schizothoracinae).
AB  - Schizothorax chongi is an endemic and important polyploidy fish in the upper
      stream of the Yangtze River. S. chongi represents a typical model species to
      study historical adaptation and evolution in the Tibetan Plateau. In this study,
      the complete mitochondrial DNA genome sequence of S. chongi was first determined
      by DNA sequencing based on the PCR fragments. The complete mitochondrial DNA
      (mtDNA) genome sequence of S. chongi is a circular molecule of 16,584 bp in
      length. It consists of 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes, and
      a control region (D-loop). The gene nucleotide composition of S. chongi is 29.6%
      A, 27.1% C, 17.9% G, and 25.4% T, with a high AT content (55.0%). The results
      could provide useful data for further studies on phylogenetics, conservation
      genetics and rational resource management for S. chongi. 

PMID- 24865917
TI  - Complete mitochondrial genome of blunt-snouted lenok Brachymystax tumensis
      (Salmoniformes, Salmonidae).
AB  - The complete mitochondrial genomes were sequenced in two individuals of blunt
      snouted lenok Brachymystax tumensis. The sizes of the genomes in the two isolates
      were 16,754 and 16,836; the difference was due to variable number of repeat
      sequences within the control region. The gene arrangement, base composition, and
      size of the two sequenced genomes are very similar to the B. lenok and B. lenok
      tsinlingensis genomes previously published (JQ686730 and JQ686731). However, the
      level of divergence inferred from 12 protein-coding genes (3.48%) indicated clear
      species boundaries between the lenok species. 

PMID- 24865918
TI  - Complete mitochondrial genome of the Trachypithecus francoisi.
AB  - In the present study, the complete mitochondrial genome of Trachypithecus
      francoisi was determined using PCR reactions. The mitochondrial genome is 16,544
      bp in length, consisting of 13 protein-coding genes, 2 ribosomal RNA genes, 22
      transfer RNA genes and a control region. The structural organization and gene
      order of T. francoisi were equivalent to that of most other vertebrates. The T.
      francoisi mtDNA could provide useful data for further studies on phylogenetics
      and conservation genetics of this species. 

PMID- 24865919
TI  - The complete mitochondrial genome of Gonepteryx mahaguru (Lepidoptera: Pieridae).
AB  - The complete mitochondrial genome of Gonepteryx mahaguru (Lepidoptera: Pieridae)
      is 15,221 bp in length, containing 13 protein-coding genes (PCGs), 22 transfer
      RNA genes (tRNAs), 2 ribosomal RNA genes (LrRNA and SrRNA) and 1 non-coding A + T
      rich region. The nucleotide composition is significantly biased toward A + T
      (80.9%). All PCGs are initiated by classical ATN codon, with the exception of
      COI, which begins with TTA codon. Nine PCGs harbor the complete stop codon TAA,
      whereas COI, COII, ND4 and ND5 stop with incomplete codons, single T or TA. All
      tRNAs can be folded into the typical cloverleaf secondary structure, except for
      tRNA(Ser)(AGN). The A + T content of AT-rich region is 95.2%, same to the highest
      one in the known species in Pieridae. 

PMID- 24865920
TI  - The complete mitochondrial genome of Pomacea canaliculata (Gastropoda:
      Ampullariidae).
AB  - The mitochondrial genome of Pomacea canaliculata (Gastropoda: Ampullariidae) is
      the first complete mtDNA sequence reported in the genus Pomacea. The total length
      of mtDNA is 15,707 bp, which containing 13 protein-coding genes, 2 ribosomal
      RNAs, 22 transfer RNAs, and a 359 bp non-coding region. The A + T content of the
      overall base composition of H-strand is 71.7% (T: 41%, C: 12.7%, A: 30.7%, G:
      15.6%). ATP6, ATP8, CO1, CO2, ND1-3, ND5, ND6, ND4L and Cyt b genes begin with
      ATG as start codon, CO3 and ND4 begin with ATA. ATP8, CO2-3, ND4L, ND2-6 and Cyt
      b genes are terminated with TAA as stop codon, ATP6, ND1, and CO1 end with TAG. A
      long non-coding region is found and a 23 bp repeat unit repeat 11 times in this
      region. 

PMID- 24865921
TI  - The complete mitochondrial genome of Glyptothorax sinense (Siluriformes,
      Sisoridae).
AB  - Glyptothorax sinense (Siluriformes, Sisoridae), is a kind of small-sized
      freshwater fish which mainly distributes in the middle and upper reaches of the
      Yangtze River in China. In this study, the complete mitochondrial genome of G.
      sinense was first determined using a PCR-based method. The complete mtDNA
      sequence is 16,531 bp in length, including 22 transfer RNA genes, 2 ribosomal RNA
      genes, 13 protein-coding genes, and a non-coding control region (D-loop). The
      overall-based composition was 31.61% A, 26.66% T, 15.38% G and 26.34% C, with a
      relatively high A + T content (58.27%). This will provide a useful tool for
      evolutionary and population genetic studies of G. sinense. 

PMID- 24865922
TI  - The complete mitochondrial genome of the Plectorhinchus cinctus (Teleostei,
      Haemulidae).
AB  - We present the complete mitochondrial genome of the Plectorhinchus cinctus in
      this study. The mitochondrial genome is 16,523 bp in length and consists of 13
      protein-coding genes, 2 rRNA genes, 22 tRNA genes and a control region. The
      nucleotide compositions of the light strand are 31.30% of C, 27.66% of A, 24.54%
      of T, and 16.50% of G. With the exception of ND6 and eight tRNA genes, all other
      mitochondrial genes are encoded on the heavy strand. All the protein-coding genes
      begin with an ATG initiation codon except for COX1 with GTG. Five types of
      termination codons revealed are TAA (ND1, ND2, ATP8, ND4L, ND5), T (COXP, ND3,
      ND4, CYTB), TA (ATP6, COXSH), AGG (COXI) and TAG (ND6). 

PMID- 24865923
TI  - Complete genome sequence of chloroplast DNA (cpDNA) of Chlorella sorokiniana.
AB  - The complete chloroplast genome sequence of Chlorella sorokiniana strain (SAG 111
      8 k) is presented in this study. The genome consists of circular chromosomes of
      109,811 bp, which encode a total of 109 genes, including 74 proteins, 3 rRNAs and
      31 tRNAs. Moreover, introns are not detected and all genes are present in single
      copy. The overall AT contents of the C. sorokiniana cpDNA is 65.9%, the coding
      sequence is 59.1% and a large inverted repeat (IR) is not observed. 

PMID- 24865924
TI  - Morbidity and mortality after distal pancreatectomy for trauma: a critical
      appraisal of 107 consecutive patients undergoing resection at a Level 1 Trauma
      Centre.
AB  - BACKGROUND: This study evaluated 30-day morbidity and mortality and assessed
      pancreas-specific complications in patients with major pancreatic injuries who
      underwent a distal pancreatectomy. STUDY DESIGN: Records of 107 consecutive
      patients who underwent a distal pancreatectomy at a Level 1 Trauma Centre in Cape
      Town between January 1982 and December 2011 were reviewed. Primary endpoints were
      postoperative morbidity and death. Complications were graded according to the
      Clavien-Dindo severity classification and the International Study Group of
      Pancreatic Surgery (ISGPS) definitions. RESULTS: A total of 107 patients [94 men,
      median age 26, median RTS 7.8, 69 penetrating injuries (63 gunshot wounds, 6
      stabs wounds), 38 blunt injuries] underwent distal pancreatectomy. Overall
      mortality was 12%, 16% for gunshot injuries, 8% for blunt trauma and 0% in
      patients who had stab wounds. Eighty patients had a post-operative complication.
      A pancreatic leak (n=26) was the most common pancreatic related complication.
      Median postoperative stay in 28 patients with no or grade I complications was 9
      days; in 11 patients with grade II complications was 18 days; in 14 grade IIIa,
      31 days; in 19 grade IIIb, 38 days; in 8 grade IVa, 33 days in 14 grade IVb, and
      in 13 grade V the duration of postoperative stay was 14+/-39.4 days. CONCLUSIONS:
      Overall mortality for distal pancreatectomy was 12%. Pancreatic leak was a common
      cause of morbidity. Length of hospitalisation increased with increasing Clavien
      Dindo severity grading. There was a significant difference in the duration of
      hospitalisation in patients with no or grade I complications compared to those
      with grade II-IV injuries (p<0.05).

PMID- 24865925
TI  - Oxidation resistance 1 is essential for protection against oxidative stress and
      participates in the regulation of aging in Caenorhabditis elegans.
AB  - Human oxidation resistance 1 (OXR1) functions in protection against oxidative
      damage and its homologs are highly conserved in eukaryotes examined so far, but
      its function still remains uncertain. In this study, we identified a homolog (LMD
      3) of human OXR1 in the nematode Caenorhabditis elegans (C. elegans). The
      expressed LMD-3 was able to suppress the mutator phenotypes of E. coli mutMmutY
      and mutT mutants. Purified LMD-3 did not have enzymatic activity against 8-oxoG,
      superoxide dismutase (SOD), or catalase activities. Interestingly, the expression
      of LMD-3 was able to suppress the methyl viologen or menadione sodium bisulfite
      induced expression of soxS and sodA genes in E. coli. The sensitivity of the C.
      elegans lmd-3 mutant to oxidative and heat stress was markedly higher than that
      of the wild-type strain N2. These results suggest that LMD-3 protects cells
      against oxidative stress. Furthermore, we found that the lifespan of the C.
      elegans lmd-3 mutant was significantly reduced compared with that of the N2,
      which was resulted from the acceleration of aging. We further examined the
      effects of deletions in other oxidative defense genes on the properties of the
      lmd-3 mutant. The deletion of sod-2 and sod-3, which are mitochondrial SODs,
      extended the lifespan of the lmd-3 mutant. These results indicate that, in
      cooperation with mitochondrial SODs, LMD-3 contributes to the protection against
      oxidative stress and aging in C. elegans.

PMID- 24865927
TI  - Salivary gland degeneration and ovary development in the Rocky Mountain wood
      tick, Dermacentor andersoni Stiles (Acari: Ixodidae). II. Determination of the
      'critical weight'.
AB  - The feeding cycle of female ixodid ticks is divided into preparatory, slow, and
      rapid feeding phases. When a female Amblyomma hebraeum is removed from the host
      after achieving a minimum size of about 10-13* the unfed weight, various
      physiological and behavioural changes occur: (a) haemolymph ecdysteroid
      concentration rises dramatically, (b) the tick does not reattach to the host when
      given the opportunity, (c) its salivary glands degenerate within about 4 days (if
      mated) or 8 days (if virgin), and (d) oocyte maturation and oviposition occur
      (Kaufman and Lomas, 1996; Invert. Repr. Devel. 30: 191-198). None of these
      changes occur if the tick is removed from the host at smaller sizes. This
      transition, which occurs when the tick enters the rapid phase of engorgement, has
      been named the 'critical weight'. To date, the critical weight has been
      determined for A. hebraeum only. The present study established that, in both
      mated and virgin D. andersoni, the critical weight is similar to that of A.
      hebraeum. Although a small percentage of virgin A. hebraeum do exceed the
      critical weight, achieving perhaps 20* the unfed weight, virgin D. andersoni
      regularly fed well beyond their CW (>50* the unfed weight) and occasionally
      engorged completely (100* the unfed weight), although they did not detach
      spontaneously from the host within 21 days of attachment. 

PMID- 24865929
TI  - Consensus development on the essential competencies for Iranian public health
      nutritionists.
AB  - OBJECTIVE: To assess key experts' opinion regarding essential competencies
      required for effective public health nutrition practice within the health-care
      system of Iran. DESIGN: Qualitative study using the modified Delphi technique
      through an email-delivered questionnaire. SETTING: Iran. SUBJECTS: Fifty-five
      experts were contacted through email. The inclusion criterion for the study panel
      was being in a relevant senior-level position in nutrition science or public
      health nutrition in Iran. RESULTS: In the first round, forty-two out of fifty
      five experts responded to the questionnaire (response rate=76 %). A sixty-five
      item questionnaire was designed with nine competency areas, including 'nutrition
      science', 'planning and implementing nutritional interventions', 'health and
      nutrition services', 'advocacy and communication', 'assessment and analysis',
      'evaluation', 'cultural, social and political aspects', 'using technology' and
      'leadership and management'. All experts who had participated in the first round
      completed a modified version of the questionnaire with seventy-seven items in the
      second round. The experts scored 'nutrition science' as the most essential
      competency area, while more applied areas such as 'management and leadership'
      were less emphasized. In both rounds, the mean difference between the opinions of
      the necessity of each area was 5.6 %. CONCLUSIONS: The Iranian experts had
      general agreement on most of the core competency areas of public health
      nutritionists. The results indicated the need for capacity building and revisions
      to educational curricula for public health nutritionist programmes, with more
      emphasis on skill-based competency development.

PMID- 24865931
TI  - Combined effects of the UGT1A1 and OATP2 gene polymorphisms as major risk factor
      for unconjugated hyperbilirubinemia in Indian neonates.
AB  - Genetic association studies have linked a number of single nucleotide
      polymorphisms (SNPs) with unconjugated hyperbilirubinemia. The present study was
      undertaken to validate the association of SNPs with development of
      hyperbilirubinemia in Indian neonates. Genotyping of five SNPs in two candidate
      genes was performed in 126 infants with hyperbilirubinemia and 181 controls by
      PCR-RFLP, Gene Scan analysis and direct DNA sequencing. Genetic polymorphisms of
      the UGT1A1 promoter, specifically the -3279 T?G phenobarbital responsive enhancer
      module (rs4124874) and (TA)7 dinucleotide repeat (rs8175347) as well as the
      coding region variants (rs2306283 and rs4149056) of the OATP2 gene were
      significantly higher among the cases than the controls. The presence of the
      mutant haplotypes either in homozygous, heterozygous or compound heterozygous
      state had a significant effect on neonatal hyperbilirubinemia as well as on the
      requirement of phototherapy than those with the wild haplotype. Further, a
      significantly higher number of hyperbilirubinemic cases had >=3 variants than the
      controls (73.80% vs 40.36%, p<0.0001) and the mean total serum bilirubin levels
      and requirement of phototherapy also increased according to the number of
      variants co-expressed. This study demonstrates that UGT1A1 and OATP2
      polymorphisms were associated with altered bilirubin metabolism and could be
      genetic risk factors for neonatal hyperbilirubinemia.

PMID- 24865932
TI  - Plant degreening: evolution and expression of tomato (Solanum lycopersicum)
      dephytylation enzymes.
AB  - Chlorophyll is the most abundant pigment on earth and even though it is known
      that its high photo-excitability necessitates a tight regulation of its
      degradation pathway, to date there are still several steps in chlorophyll
      breakdown that remain obscure. In order to better understand the 'degreening'
      processes that accompany leaf senescence and fruit ripening, we characterized the
      enzyme-encoding genes involved in dephytylation from tomato (Solanum
      lycopersicum). A single pheophytinase (PPH) gene and four chlorophyllase (CLH)
      genes were identified in the tomato genome. A phenetic analysis revealed two
      groups of CLHs in eudicot species and further evolutionary analysis indicated
      that these enzymes are under diverse selection pressures. A comprehensive
      expression profile analysis also suggested functional specificity for these
      dephytylating enzymes. The integrated analysis allows us to propose three general
      roles for chlorophyll dephytylation: i) PPH, which is under high selective
      constraint, is responsible for chlorophyll degradation during developmentally
      programed physiological processes; ii) Group I CLHs, which are under relaxed
      selection constraint, respond to environmental and hormonal stimuli and play a
      role in plant adaptation plasticity; and iii) Group II CLHs, which are also under
      high selective constraint, are mostly involved in chlorophyll recycling. 

PMID- 24865933
TI  - Identification and catalytic characterization of a nonribosomal peptide
      synthetase-like (NRPS-like) enzyme involved in the biosynthesis of echosides from
      Streptomyces sp. LZ35.
AB  - Echosides, isolated from Streptomyces sp. LZ35, represent a class of para
      terphenyl natural products that display DNA topoisomerase I and IIalpha
      inhibitory activities. By analyzing the genome draft of strain LZ35, the ech gene
      cluster was identified to be responsible for the biosynthesis of echosides, which
      was further confirmed by gene disruption and HPLC analysis. Meanwhile, the
      biosynthetic pathway for echosides was proposed. Furthermore, the echA-gene,
      encoding a tri-domain nonribosomal peptide synthetase (NRPS)-like enzyme, was
      identified as a polyporic acid synthetase and biochemically characterized in
      vitro. This is the first study to our knowledge on the biochemical
      characterization of an Actinobacteria quinone synthetase, which accepts
      phenylpyruvic acid as a native substrate. Therefore, our results may help
      investigate the function of other NRPS-like enzymes in Actinobacteria. 

PMID- 24865934
TI  - Comparison of Acetyl-CoA carboxylase 1 (Acc-1) gene diversity among different
      Triticeae genomes.
AB  - It has widely been documented that life form and mating system have significant
      influences on genetic diversity. In the tribe Triticeae, several genera contain
      both annual and perennial species, whereas other genera comprise strictly annual
      or perennial species. It was suggested that Triticeae annuals have originated
      from Triticeae perennials. The present study aims to analyze nucleotide diversity
      of Acc-1 gene among different Triticeae genomes, and attempts to link effects of
      life history (annuals and perennials) and mating systems. The nucleotide
      diversity of 364 Acc-1 sequences in Triticeae species was characterized. The
      highest estimates of nucleotide diversity values (pi=0.01919, theta=0.03515) were
      found for the Ns genome among the genomes analyzed. Nucleotide diversities in the
      D genome and Ns genome of polyploids are higher than those in respective genomes
      of diploids, while in the St genome of polyploids, it is lower than that in the
      St genome of diploids. The averaged pi value (0.013705) in the genomes of
      perennials is more than twice of the value (0.00508) in the genomes of annuals.
      The averaged pi value (0.01323) in the genomes of outcrossing species is two-fold
      of the value (0.005664) in the genomes of selfer. Our results suggested that the
      evolutionary history and mating system may play an important role in determining
      nucleotide diversity of Acc-1 gene in each genome.

PMID- 24865936
TI  - Equilibrium folding of pro-HlyA from Escherichia coli reveals a stable calcium
      ion dependent folding intermediate.
AB  - HlyA from Escherichia coli is a member of the repeats in toxin (RTX) protein
      family, produced by a wide range of Gram-negative bacteria and secreted by a
      dedicated Type 1 Secretion System (T1SS). RTX proteins are thought to be secreted
      in an unfolded conformation and to fold upon secretion by Ca(2+) binding.
      However, the exact mechanism of secretion, ion binding and folding to the correct
      native state remains largely unknown. In this study we provide an easy protocol
      for high-level pro-HlyA purification from E. coli. Equilibrium folding studies,
      using intrinsic tryptophan fluorescence, revealed the well-known fact that Ca(2+)
      is essential for stability as well as correct folding of the whole protein. In
      the absence of Ca(2+), pro-HlyA adopts a non-native conformation. Such molecules
      could however be rescued by Ca(2+) addition, indicating that these are not dead
      end species and that Ca(2+) drives pro-HlyA folding. More importantly, pro-HlyA
      unfolded via a two-state mechanism, whereas folding was a three-state process.
      The latter is indicative of the presence of a stable folding intermediate.
      Analysis of deletion and Trp mutants revealed that the first folding transition,
      at 6-7M urea, relates to Ca(2+) dependent structural changes at the extreme C
      terminus of pro-HlyA, sensed exclusively by Trp914. Since all Trp residues of
      HlyA are located outside the RTX domain, our results demonstrate that Ca(2+)
      induced folding is not restricted to the RTX domain. Taken together, Ca(2+)
      binding to the pro-HlyA RTX domain is required to drive the folding of the entire
      protein to its native conformation. 

PMID- 24865935
TI  - Characterization of the canine mda-7 gene, transcripts and expression patterns.
AB  - Human melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24)
      displays potent growth suppressing and cell killing activity against a wide
      variety of human and rodent cancer cells. In this study, we identified a canine
      ortholog of the human mda-7/IL-24 gene located within a cluster of IL-10 family
      members on chromosome 7. The full-length mRNA sequence of canine mda-7 was
      determined, which encodes a 186-amino acid protein that has 66% similarity to
      human MDA-7/IL-24. Canine MDA-7 is constitutively expressed in cultured normal
      canine epidermal keratinocytes (NCEKs), and its expression levels are increased
      after lipopolysaccharide stimulation. In cultured NCEKs, the canine mda-7 pre
      mRNA is differentially spliced, via exon skipping and alternate 5'-splice donor
      sites, to yield five splice variants (canine mda-7sv1, canine mda-7sv2, canine
      mda-7sv3, canine mda-7sv4 and canine mda-7sv5) that encode four protein isoforms
      of the canine MDA-7 protein. These protein isoforms have a conserved N-terminus
      (signal peptide sequence) and are dissimilar in amino acid sequences at their C
      terminus. Canine MDA-7 is not expressed in primary canine tumor samples, and most
      tumor derived cancer cell lines tested, like its human counterpart. Unlike human
      MDA-7/IL-24, canine mda-7 mRNA is not expressed in unstimulated or
      lipopolysaccharide (LPS), concanavalin A (ConA) or phytohemagglutinin (PHA)
      stimulated canine peripheral blood mononuclear cells (PBMCs). Furthermore, in
      silico analysis revealed that canonical canine MDA-7 has a potential 28 amino
      acid signal peptide sequence that can target it for active secretion. This data
      suggests that canine mda-7 is indeed an ortholog of human mda-7/IL-24, its
      protein product has high amino acid similarity to human MDA-7/IL-24 protein and
      it may possess similar biological properties to human MDA-7/IL-24, but its
      expression pattern is more restricted than its human ortholog. 

PMID- 24865937
TI  - Rheological characterization of cataplasm bases composed of cross-linked
      partially neutralized polyacrylate hydrogel.
AB  - Viscoelasticity is a useful parameter for characterizing the intrinsic properties
      of the cross-linked polyacrylate hydrogel used in cataplasm bases. The aim of
      this study was to investigate the effects of various formulation parameters on
      the rheological characteristics of polyacrylate hydrogel. The hydrogel layers
      were formed using a partially neutralized polyacrylate (Viscomate(TM)), which
      contained acrylic acid and sodium acrylate in different copolymerization ratios,
      as the cross-linked gel framework. Dihydroxyaluminum aminoacetate (DAAA), which
      produces aluminum ions, was used as the cross-linking agent. Rheological analyses
      were performed using a "stress amplitude sweep" and a "frequency sweep". The
      results showed that greater amounts of acrylic acid in the structure of Viscomate
      as well as higher concentrations of DAAA and Viscomate led to an increase in the
      elastic modulus (G'). However, greater amounts of acrylic acid in the structure
      of Viscomate and higher concentrations of DAAA had an opposite on the viscous
      modulus (G"); this might be owing to higher steric hindrance. The results of this
      study can serve as guidelines for the optimization of formulations for
      cataplasms. 

PMID- 24865938
TI  - C-arm cone-beam computed tomography needle path overlay for percutaneous biopsy
      of pulmonary nodules.
AB  - PURPOSE: The aim of this study was to evaluate the feasibility of percutaneous
      transthoracic needle biopsy of pulmonary nodules under cone-beam computed
      tomography (CBCT) with "XperGuide" navigation guidance. MATERIALS AND METHODS:
      From February 2010 to January 2012, 100 patients (63 men and 37 women; mean age
      67.27 years; range 21-88 years) with 100 lung nodules (44 <= 3 cm, 56 > 3 cm)
      underwent CBCT-XperGuide guided percutaneous transthoracic needle biopsies.
      Technical success, diagnostic accuracy, sensitivity, specificity, positive
      predictive value (PPV), negative predictive value (NPV) and complications were
      evaluated. RESULTS: Of 100 nodules (mean size 5.19 cm), 68 were diagnosed as
      malignant, 27 as benign, and five as indeterminate. Technical success was 95 %.
      Only 33 of 100 patients underwent surgery: the final pathological diagnosis was
      concordant with the biopsy diagnosis in 26 cases and discordant in 7 cases (false
      negatives). Accuracy, sensitivity, specificity, PPV and NPV were 92.6, 90.9, 100,
      100 and 72 %, respectively. CONCLUSIONS: CBCT-XperGuide navigation is a new,
      accurate and safe imaging guidance for percutaneous lung biopsies.

PMID- 24865939
TI  - Emergency contrast-enhanced ultrasonography for pancreatic injuries in blunt
      abdominal trauma.
AB  - PURPOSE: The purpose of this study was to retrospectively investigate the
      application of emergency contrast-enhanced ultrasonography (CEUS) in blunt
      pancreatic trauma. MATERIALS AND METHODS: Twenty-two consecutive patients with
      blunt pancreatic trauma were examined using CEUS from March 2007 to June 2012.
      The findings of CEUS were compared with those of contrast-enhanced computed
      tomography scans at level-1 diagnostic tests. RESULTS: Out of the 22 patients, 21
      were diagnosed with blunt pancreatic injury using CEUS, including 8 patients with
      lesions in the neck of pancreas, 9 in the body, 3 in the tail and 1 in the head.
      The injury sites appeared as anechoic and/or hypoechoic perfusion defect regions
      with irregular borders in parenchyma and capsule on CEUS images. The lesion sizes
      measured by CEUS were 1.88 +/- 0.81 cm, which were consistent with the 1.93 +/-
      0.77 cm measured by CT (p > 0.05). Using CT as a reference standard, the
      detection rate of CEUS in blunt pancreatic trauma was 95.5 % (21/22).
      CONCLUSIONS: CEUS findings can be used to provide a reliable diagnosis for blunt
      pancreatic trauma. CEUS is thus promising in the assessment of blunt pancreatic
      trauma, especially in institutions where emergency CEUS is used as an initial
      diagnostic instrument.

PMID- 24865940
TI  - Heme-related molecules induce rapid production of neutrophil extracellular traps.
AB  - BACKGROUND: Pulmonary endothelial cell damages caused by neutrophil
      overactivation could result in acute lung injuries including transfusion-related
      acute lung injury (TRALI). We previously reported that heme-related molecules
      derived from hemolysis induced the production of reactive oxygen species from
      neutrophils. Recently, neutrophil extracellular traps (NETs) have been
      demonstrated to associate with the onset of TRALI. STUDY DESIGN AND METHODS: In
      this study, neutrophils' morphologic changes induced by the heme-related molecule
      hemin were confirmed to be NETs via confocal laser scanning microscopy and
      electron microscopy (EM). Additionally, concentrations of hemin in red blood cell
      (RBC) components were measured via enzyme-linked immunosorbent assay and possible
      contribution of these molecules to the onset of TRALI was discussed. RESULTS:
      SYTOX green staining observation via confocal laser scanning microscopy revealed
      that neutrophil morphology changed rapidly upon addition of hemin. The nuclei
      began to be enlarged and become segmented after 5 minutes, and NET-like
      structures were released from neutrophils after 15 minutes. In EM observation,
      NET-like structures appeared after 10 minutes and the nucleoplasm was partially
      separated from the nuclear membrane, which were consistent with the features of
      NET formation. These structures stained positively for both myeloperoxidase and
      histone H3 antibodies. CONCLUSION: Thus, our results suggest that hemin induced
      NETs in 15 minutes, a quicker reaction than NET induction by phorbol myristate
      acetate requiring 3 hours. Moreover, since RBC components, especially those with
      long-term storage, contained sufficient hemin concentration to induce NETs,
      special attention to hemolysis of stored RBC components is important.

PMID- 24865942
TI  - Effect of changes to cost and availability of emergency contraception on users'
      profiles in an emergency department in Catalunya.
AB  - OBJECTIVE: Emergency contraception (EC) accessibility has evolved differently in
      Catalunya as compared with other autonomous communities in Spain. Free-of-charge
      access within the Public Health System was authorised in 2004, and over-the
      counter (OTC) access was implemented in 2009. The aim of the study is to assess
      the impact of these measures on demand and users' profiles at our institution.
      METHODS: A retrospective study, in our Emergency Department, was conducted to
      evaluate EC requests in relationship to accessibility modifications. The age of
      women and which days of the week they attended were analysed. RESULTS: The number
      of EC requests, the distribution by age and the demand over the week remained
      stable after access to EC became free of charge. However, requests sharply
      decreased following OTC access implementation. Distribution by age also changed,
      with a significant increase in requests from women under 25 years (72% vs 56%, p
      < 0.001). Demand was greatest on Sunday and Monday, and this distribution
      persisted over the study period. CONCLUSION: EC requests remained unchanged
      following free-of-charge access to EC, but decreased after OTC implementation.
      Women currently seeking EC at no cost at our institution are more likely to be
      younger and to request it on a Monday.

PMID- 24865943
TI  - Structure-activity relationship of nonsecosteroidal vitamin D receptor
      modulators.
AB  - The vitamin D receptor (VDR), a receptor for the secosteroid 1alpha,25
      dihydroxyvitamin D3 [1,25(OH)2D3], is a promising drug target in the treatment of
      bone and mineral disorders, cancer, autoimmune disease, infection, and
      cardiovascular disease. Indeed, approximately 100 nonsecosteroidal VDR modulators
      (VDRMs) have been developed. Analysis of X-ray crystal structures reveals: (i)
      nonsecosteroidal VDRMs bind to VDR in a position similar to 1,25(OH)2D3; (ii)
      hydrogen bond interactions between ligands and VDR are the most important for VDR
      binding; (iii) hydrophobic interactions and CH-pi interactions in aromatic
      ligands are also important for VDR binding; and (iv) exchange of C-O-C linkage to
      C-CH2-C linkage in VDRMs increases transactivation activity, probably as a result
      of an entropic effect of solvation/desolvation of molecules. Several VDRMs have
      better therapeutic efficacy when compared to 1,25(OH)2D3 in experimental models
      of cancer and osteoporosis with less induction of hypercalcemia, a major
      potential adverse effect in the clinical application of VDR ligands. 

PMID- 24865945
TI  - Correlation of electrical conductance in meridian and autonomic nervous activity
      after auricular acupressure in middle-aged women.
AB  - BACKGROUND: This study aimed to examine the correlation of heart rate variability
      (HRV) and meridian electrical conductance among middle-aged women during an 8
      week period of auricular acupressure (AA) treatment for weight reduction.
      METHODS: Sixty (60) subjects were randomized either to a control group (n=30) or
      to a treatment group with AA (n=30). Anthropometric parameters, HRV indices, and
      meridian levels were measured before treatment, at the 5th week, and 1 week after
      the 8-week treatment period. RESULTS: Although no significant changes were
      observed in body weight (BW) and body-mass index (BMI) from baseline to 1 week
      after AA treatment, a significant decrease in Waist Circumference (WC) was
      observed in the acupressure group. In contrast, the subjects' BW, BMI, and WC
      were significantly increased from baseline to the 9th week in the control group.
      With adjustment for baseline low frequencies (LF) of HRV, the LF at the 5th and
      9th weeks in the acupressure groups was generally lower than that in the control
      group, with a p-value=0.027 using the mixed linear model. The meridian levels for
      Spleen, Bladder, and Gallbladder were significantly lower in the group subjected
      to acupressure than in the control group at the 5th week. CONCLUSIONS: The
      results of the present study indicate that AA tends to inactivate the sympathetic
      nervous activity demonstrated by both HRV and meridian electrical conductance
      changes. As a result, AA may modulate the autonomic nervous system to exert its
      physiological effect through the pathway of the meridian system.

PMID- 24865944
TI  - Alcohol dependence: molecular and behavioral evidence.
AB  - Alcohol dependence is a complex condition with clear genetic factors. Some of the
      leading candidate genes code for subunits of the inhibitory GABAA and glycine
      receptors. These and related ion channels are also targets for the acute actions
      of alcohol, and there is considerable progress in understanding interactions of
      alcohol with these proteins at the molecular and even atomic levels. X-ray
      structures of open and closed states of ion channels combined with structural
      modeling and site-directed mutagenesis have elucidated direct actions of alcohol.
      Alcohol also alters channel function by translational and post-translational
      mechanisms, including phosphorylation and protein trafficking. Construction of
      mutant mice with either deletion of key proteins or introduction of alcohol
      resistant channels has further linked specific proteins with discrete behavioral
      effects of alcohol. A combination of approaches, including genome wide
      association studies in humans, continues to advance the molecular basis of
      alcohol action on receptor structure and function. 

PMID- 24865949
TI  - Reaction mechanism of Ru(II) piano-stool complexes: umbrella sampling QM/MM MD
      study.
AB  - Biologically relevant interactions of piano-stool ruthenium(II) complexes with ds
      DNA are studied in this article by hybrid quantum mechanics-molecular mechanics
      (QM/MM) computational technique. The whole reaction mechanism is divided into
      three phases: (i) hydration of the [Ru(II) (eta(6) -benzene)(en)Cl](+) complex,
      (ii) monoadduct formation between the resulting aqua-Ru(II) complex and N7
      position of one of the guanines in the ds-DNA oligomer, and (iii) formation of
      the intrastrand Ru(II) bridge (cross-link) between two adjacent guanines. Free
      energy profiles of all the reactions are explored by QM/MM MD umbrella sampling
      approach where the Ru(II) complex and two guanines represent a quantum core,
      which is described by density functional theory methods. The combined QM/MM
      scheme is realized by our own software, which was developed to couple several
      quantum chemical programs (in this study Gaussian 09) and Amber 11 package.
      Calculated free energy barriers of the both ruthenium hydration and Ru(II)-N7(G)
      DNA binding process are in good agreement with experimentally measured rate
      constants. Then, this method was used to study the possibility of cross-link
      formation. One feasible pathway leading to Ru(II) guanine-guanine cross-link with
      synchronous releasing of the benzene ligand is predicted. The cross-linking is an
      exergonic process with the energy barrier lower than for the monoadduct reaction
      of Ru(II) complex with ds-DNA.

PMID- 24865948
TI  - Extracellular ATP is a central signaling molecule in plant stress responses.
AB  - Because of their sessile nature, plants have developed a number of sophisticated
      signaling systems to adapt to environmental changes. Previous research has shown
      that extracellular ATP is an important signaling molecule used by plants and
      functions in a variety of processes, including growth, development, and stress
      responses. Recently, DORN1 was identified as the first plant purinoceptor,
      essential for the plant response to ATP. The identification of the receptor is a
      milestone for our overall understanding of various physiological events regulated
      by extracellular ATP. In this review, we will discuss the possible roles of DORN1
      providing future direction for research into the role of extracellular ATP in
      plants. 

PMID- 24865950
TI  - "The quantification with FDG as seen by a physician." Nucl Med Biol 2013;40:720
      30.

PMID- 24865947
TI  - The structure, function and properties of sirohaem decarboxylase--an enzyme with
      structural homology to a transcription factor family that is part of the
      alternative haem biosynthesis pathway.
AB  - Some bacteria and archaea synthesize haem by an alternative pathway, which
      involves the sequestration of sirohaem as a metabolic intermediate rather than as
      a prosthetic group. Along this pathway the two acetic acid side-chains attached
      to C12 and C18 are decarboxylated by sirohaem decarboxylase, a heterodimeric
      enzyme composed of AhbA and AhbB, to give didecarboxysirohaem. Further
      modifications catalysed by two related radical SAM enzymes, AhbC and AhbD,
      transform didecarboxysirohaem into Fe-coproporphyrin III and haem respectively.
      The characterization of sirohaem decarboxylase is reported in molecular detail.
      Recombinant versions of Desulfovibrio desulfuricans, Desulfovibrio vulgaris and
      Methanosarcina barkeri AhbA/B have been produced and their physical properties
      compared. The D. vulgaris and M. barkeri enzyme complexes both copurify with
      haem, whose redox state influences the activity of the latter. The kinetic
      parameters of the D. desulfuricans enzyme have been determined, the enzyme
      crystallized and its structure has been elucidated. The topology of the enzyme
      reveals that it shares a structural similarity to the AsnC/Lrp family of
      transcription factors. The active site is formed in the cavity between the two
      subunits and a AhbA/B-product complex with didecarboxysirohaem has been obtained.
      A mechanism for the decarboxylation of the kinetically stable carboxyl groups is
      proposed. 

PMID- 24865951
TI  - Predicting emotional exhaustion among haemodialysis nurses: a structural equation
      model using Kanter's structural empowerment theory.
AB  - AIM: To test an explanatory model of the relationships between the nursing work
      environment, job satisfaction, job stress and emotional exhaustion for
      haemodialysis nurses, drawing on Kanter's theory of organizational empowerment.
      BACKGROUND: Understanding the organizational predictors of burnout (emotional
      exhaustion) in haemodialysis nurses is critical for staff retention and improving
      nurse and patient outcomes. Previous research has demonstrated high levels of
      emotional exhaustion among haemodialysis nurses, yet the relationships between
      nurses' work environment, job satisfaction, stress and emotional exhaustion in
      this population are poorly understood. DESIGN: A cross-sectional online survey.
      METHODS: 417 nurses working in haemodialysis units completed an online survey
      between October 2011-April 2012 using validated measures of the work environment,
      job satisfaction, job stress and emotional exhaustion. RESULTS: Overall, the
      structural equation model demonstrated adequate fit and we found partial support
      for the hypothesized relationships. Nurses' work environment had a direct
      positive effect on job satisfaction, explaining 88% of the variance. Greater job
      satisfaction, in turn, predicted lower job stress, explaining 82% of the
      variance. Job satisfaction also had an indirect effect on emotional exhaustion by
      mitigating job stress. However, job satisfaction did not have a direct effect on
      emotional exhaustion. CONCLUSION: The work environment of haemodialysis nurses is
      pivotal to the development of job satisfaction. Nurses' job satisfaction also
      predicts their level of job stress and emotional exhaustion. Our findings suggest
      staff retention can be improved by creating empowering work environments that
      promote job satisfaction among haemodialysis nurses.

PMID- 24865952
TI  - Pneumatic microvalve-based hydrodynamic sample injection for high-throughput,
      quantitative zone electrophoresis in capillaries.
AB  - A hybrid microchip/capillary electrophoresis (CE) system was developed to allow
      unbiased and lossless sample loading and high-throughput repeated injections.
      This new hybrid CE system consists of a poly(dimethylsiloxane) (PDMS) microchip
      sample injector featuring a pneumatic microvalve that separates a sample
      introduction channel from a short sample loading channel, and a fused-silica
      capillary separation column that connects seamlessly to the sample loading
      channel. The sample introduction channel is pressurized such that when the
      pneumatic microvalve opens briefly, a variable-volume sample plug is introduced
      into the loading channel. A high voltage for CE separation is continuously
      applied across the loading channel and the fused-silica capillary separation
      column. Analytes are rapidly separated in the fused-silica capillary, and
      following separation, high-sensitivity MS detection is accomplished via a
      sheathless CE/ESI-MS interface. The performance evaluation of the complete CE/ESI
      MS platform demonstrated that reproducible sample injection with well controlled
      sample plug volumes could be achieved by using the PDMS microchip injector. The
      absence of band broadening from microchip to capillary indicated a minimum dead
      volume at the junction. The capabilities of the new CE/ESI-MS platform in
      performing high-throughput and quantitative sample analyses were demonstrated by
      the repeated sample injection without interrupting an ongoing separation and a
      linear dependence of the total analyte ion abundance on the sample plug volume
      using a mixture of peptide standards. The separation efficiency of the new
      platform was also evaluated systematically at different sample injection times,
      flow rates, and CE separation voltages. 

PMID- 24865957
TI  - [Allergic rhinitis in pregnancy].

PMID- 24865953
TI  - Characteristics of patients with mild to moderate primary pulmonary
      coccidioidomycosis.
AB  - In Arizona, USA, primary pulmonary coccidioidomycosis accounts for 15%-29% of
      community-acquired pneumonia. To determine the evolution of symptoms and changes
      in laboratory values for patients with mild to moderate coccidioidomycosis during
      2010-2012, we conducted a prospective 24-week study of patients with primary
      pulmonary coccidioidomycosis. Of the 36 patients, 16 (44%) were men and 33 (92%)
      were White. Median age was 53 years, and 20 (56%) had received antifungal
      treatment at baseline. Symptom scores were higher for patients who received
      treatment than for those who did not. Median times from symptom onset to 50%
      reduction and to complete resolution for patients in treatment and nontreatment
      groups were 9.9 and 9.1 weeks, and 18.7 and 17.8 weeks, respectively. Median
      times to full return to work were 8.4 and 5.7 weeks, respectively. One patient
      who received treatment experienced disseminated infection. For otherwise healthy
      adults with acute coccidioidomycosis, convalescence was prolonged, regardless of
      whether they received antifungal treatment. 

PMID- 24865958
TI  - [Pregnancy and eye].

PMID- 24865954
TI  - Mitochondrial dysfunction in central nervous system white matter disorders.
AB  - Defects of mitochondrial respiration and function had been proposed as a major
      culprit in the most common neurodegenerative diseases, including prototypic
      diseases of central nervous system (CNS) white matter such as multiple sclerosis.
      The importance of mitochondria for white matter is best exemplified in a group of
      defects of the mitochondria oxidative metabolism called mitochondria
      leukoencephalopathies or encephalomyopathies. These diseases are clinically and
      genetically heterogeneous, given the dual control of the respiratory chain by
      nuclear and mitochondrial DNA, which makes the precise diagnosis and
      classification challenging. Our understanding of disease pathogenesis is nowadays
      still limited. Here, we review current knowledge on pathogenesis and genetics,
      outlining diagnostic clues for the various forms of mitochondria disease. In
      particular, we underscore the value of magnetic resonance imaging (MRI) for the
      differential diagnosis of specific types of mitochondrial leukoencephalopathies,
      such as genetic defects on SDHFA1. The use of novel technologies for gene
      identification, such as whole-exome sequencing studies, is expected to shed light
      on novel molecular etiologies, broadening prenatal diagnosis, disease
      understanding, and therapeutic options. Current treatments are mostly palliative,
      but very promising novel gene and pharmacologic therapies are emerging, which may
      also benefit a growing list of secondary mitochondriopathies, such as the
      peroxisomal disease adrenoleukodystrophy.

PMID- 24865959
TI  - [Japanese guideline for diagnosis and management of occupational allergic
      diseases 2013 -occupational asthma-].

PMID- 24865960
TI  - [Urticaria and anaphylaxis during anesthesia].

PMID- 24865961
TI  - [Status of children with food allergy who were prescribed an adrenaline
      autoinjector (epipen)].
AB  - PURPOSE: Both to evaluate the characteristics of food allergic children who were
      prescribed an adrenaline autoinjector and to assess whether it was used
      appropriately. METHODS: The characteristics of food allergic children who were
      prescribed an adrenaline autoinjector were investigated. Among these children,
      those who experienced severe anaphylaxis due to inadvertent ingestion were
      analyzed, as was whether and how the autoinjector was used. RESULTS: An
      adrenaline autoinjector was prescribed to 139 food allergic children, most often
      for egg, followed by milk and wheat allergies. Concomitant bronchial asthma,
      atopic dermatitis, and food allergies of other causes were present in 49 (35.3%),
      68 (48.9%), and 102 cases (73.4%), respectively. The most frequent organ involved
      in anaphylaxis was the skin (94.2%), followed by the respiratory (78.5%),
      digestive (28.1%), and circulatory (24.8%) organs. A total of 24 cases
      experienced severe anaphylaxis after the prescription; however, the autoinjector
      was used in only six (25%) of those cases. The reasons given for lack of use
      included fear of use, unavailability of the autoinjector, prior improvement with
      use of an oral antihistamine and immediate visit to a hospital emergency
      department in eight, five, three and one case, respectively. CONCLUSION: These
      results suggest that the autoinjector is often not used appropriately after
      prescription. Therefore, children and their caregivers require more effective
      guidance on proper adrenaline autoinjector use.

PMID- 24865962
TI  - Geographic variation in heart failure trials: time for scepticism?

PMID- 24865963
TI  - Overexpression of microRNA-125b sensitizes human hepatocellular carcinoma cells
      to 5-fluorouracil through inhibition of glycolysis by targeting hexokinase II.
AB  - 5-fluorouracil (5-FU)-based chemotherapy is widely used in the treatment of human
      hepatocellular carcinoma. However, despite impressive initial clinical responses,
      the majority of patients eventually develop resistance to 5-FU. The microRNA
      (miR)-125 family has been implicated in a variety of carcinomas as either a tumor
      suppressor or promoter. In the present study, the role of miR-125b in acquired 5
      FU resistance in multiple human hepatocellular carcinoma cell lines was
      investigated using transfection of miR-125b. Compared with 5-FU?sensitive cells,
      5?FU?resistant cells exhibited reduced expression levels of miR?125b.
      Furthermore, transfection of pre?miR-125b into liver cancer cells resulted in
      sensitization of 5-FU?resistant cells to 5-FU. In addition, the glucose uptake
      and lactate production in 5-FU?resistant liver cancer cells were demonstrated to
      be significantly increased compared with 5?FU?sensitive cells (P<0.05),
      indicating that targeting glycolytic pathways may overcome chemoresistance in
      human liver cancer cells. Notably, miR-125 was found to downregulate glucose
      metabolism by directly targeting hexokinase II. Since drug resistance is a common
      phenotype of malignant cancer cells, the finding that miR-125b expression levels
      are negatively correlated with 5-FU resistance in hepatocellular carcinoma cells
      is consistent with the reported functions of miR-125b. In conclusion, the present
      study identified miR-125b as a tumor suppressor-like microRNA, which exhibits
      great potential as a diagnostic and prognostic biomarker in hepatocellular
      carcinoma. 

PMID- 24865964
TI  - The effect of training in an interactive dynamic stander on ankle dorsiflexion
      and gross motor function in children with cerebral palsy.
AB  - OBJECTIVE: To study the effect of active stretching of ankle plantarflexors using
      an interactive dynamic stander in children with cerebral palsy (CP). METHODS: Six
      children in Gross Motor Function Classification System classes I-III, aged 4-10
      years, trained intensive active dorsiflexion in an interactive dynamic stander
      using ankle movement to play custom computer games following a 10-week control
      period. Gross Motor Function Measure Item Set, gait performance and passive and
      active dorsiflexion with extended and flexed knee were chosen as outcome
      parameters. RESULTS: Median active and passive ankle dorsiflexion increased
      significantly (5 and 10 degrees, respectively) with extended knee. There was a
      small but clinically significant increase in gross motor function. The
      intervention had no effect on temporospatial gait parameters. CONCLUSION: In
      spite of the low number of participants, these results may indicate that
      intensive active stretching in an interactive dynamic stander could be an
      effective new conservative clinical treatment of ankle plantarflexor contracture
      in children with CP.

PMID- 24865965
TI  - Inactivation of Rb and E2f8 synergizes to trigger stressed DNA replication during
      erythroid terminal differentiation.
AB  - Rb is critical for promoting cell cycle exit in cells undergoing terminal
      differentiation. Here we show that during erythroid terminal differentiation, Rb
      plays a previously unappreciated and unorthodox role in promoting DNA replication
      and cell cycle progression. Specifically, inactivation of Rb in erythroid cells
      led to stressed DNA replication, increased DNA damage, and impaired cell cycle
      progression, culminating in defective terminal differentiation and anemia.
      Importantly, all of these defects associated with Rb loss were exacerbated by the
      concomitant inactivation of E2f8. Gene expression profiling and chromatin
      immunoprecipitation (ChIP) revealed that Rb and E2F8 cosuppressed a large array
      of E2F target genes that are critical for DNA replication and cell cycle
      progression. Remarkably, inactivation of E2f2 rescued the erythropoietic defects
      resulting from Rb and E2f8 deficiencies. Interestingly, real-time quantitative
      PCR (qPCR) on E2F2 ChIPs indicated that inactivation of Rb and E2f8 synergizes to
      increase E2F2 binding to its target gene promoters. Taken together, we propose
      that Rb and E2F8 collaborate to promote DNA replication and erythroid terminal
      differentiation by preventing E2F2-mediated aberrant transcriptional activation
      through the ability of Rb to bind and sequester E2F2 and the ability of E2F8 to
      compete with E2F2 for E2f-binding sites on target gene promoters.

PMID- 24865966
TI  - Mitochondrial matrix Ca2+ accumulation regulates cytosolic NAD+/NADH metabolism,
      protein acetylation, and sirtuin expression.
AB  - Mitochondrial calcium uptake stimulates bioenergetics and drives energy
      production in metabolic tissue. It is unknown how a calcium-mediated acceleration
      in matrix bioenergetics would influence cellular metabolism in glycolytic cells
      that do not require mitochondria for ATP production. Using primary human
      endothelial cells (ECs), we discovered that repetitive cytosolic calcium signals
      (oscillations) chronically loaded into the mitochondrial matrix. Mitochondrial
      calcium loading in turn stimulated bioenergetics and a persistent elevation in
      NADH. Rather than serving as an impetus for mitochondrial ATP generation, matrix
      NADH rapidly transmitted to the cytosol to influence the activity and expression
      of cytosolic sirtuins, resulting in global changes in protein acetylation. In
      endothelial cells, the mitochondrion-driven reduction in both the cytosolic and
      mitochondrial NAD(+)/NADH ratio stimulated a compensatory increase in SIRT1
      protein levels that had an anti-inflammatory effect. Our studies reveal the
      physiologic importance of mitochondrial bioenergetics in the metabolic regulation
      of sirtuins and cytosolic signaling cascades. 

PMID- 24865968
TI  - HuR regulates alternative splicing of the TRA2beta gene in human colon cancer
      cells under oxidative stress.
AB  - Hu antigen R (HuR) regulates stress responses through stabilizing and/or
      facilitating the translation of target mRNAs. The human TRA2beta gene encodes
      splicing factor transformer 2beta (Tra2beta) and generates 5 mRNA isoforms
      (TRA2beta1 to -5) through alternative splicing. Exposure of HCT116 colon cancer
      cells to sodium arsenite stimulated checkpoint kinase 2 (Chk2)- and mitogen
      activated protein kinase p38 (p38(MAPK))-mediated phosphorylation of HuR at
      positions S88 and T118. This induced an association between HuR and the 39
      nucleotide (nt) proximal region of TRA2beta exon 2, generating a TRA2beta4 mRNA
      that includes exon 2, which has multiple premature stop codons. HuR knockdown or
      Chk2/p38(MAPK) double knockdown inhibited the arsenite-stimulated production of
      TRA2beta4 and increased Tra2beta protein, facilitating Tra2beta-dependent
      inclusion of exons in target pre-mRNAs. The effects of HuR knockdown or
      Chk2/p38(MAPK) double knockdown were also confirmed using a TRA2beta minigene
      spanning exons 1 to 4, and the effects disappeared when the 39-nt region was
      deleted from the minigene. In endogenous HuR knockdown cells, the overexpression
      of a HuR mutant that could not be phosphorylated (with changes of serine to
      alanine at position 88 [S88A], S100A, and T118A) blocked the associated TRA2beta4
      interaction and TRA2beta4 generation, while the overexpression of a
      phosphomimetic HuR (with mutations S88D, S100D, and T118D) restored the TRA2beta4
      related activities. Our findings revealed the potential role of nuclear HuR in
      the regulation of alternative splicing programs under oxidative stress.

PMID- 24865969
TI  - Human marrow stromal cells downsize the stem cell fraction of lung cancers by
      fibroblast growth factor 10.
AB  - The functional interplay between cancer cells and marrow stromal cells (MSCs) has
      attracted a great deal of interest due to the MSC tropism for tumors but remains
      to be fully elucidated. In this study, we investigated human MSC-secreted
      paracrine factors that appear to have critical functions in cancer stem cell
      subpopulations. We show that MSC-conditioned medium reduced the cancer stem cell
      enriched subpopulation, which was detected as a side population and quiescent
      (G0) cell cycle fraction in human lung cancer cells by virtue of fibroblast
      growth factor 10 (FGF10). This reduction of the stem cell-enriched fraction was
      also observed in lung cancer cells supplemented with recombinant human FGF10
      protein. Moreover, supplementary FGF10 attenuated the expression of stemness
      genes encoding transcription factors, such as OCT3/4 and SOX2, and crippled the
      self-renewal capacity of lung cancer cells, as evidenced by the impaired
      formation of floating spheres in the suspension culture. We finally confirmed the
      therapeutic potential of the FGF10 treatment, which rendered lung cancer cells
      prone to a chemotherapeutic agent, probably due to the reduced cancer stem cell
      subpopulation. Collectively, these results add further clarification to the
      molecular mechanisms underlying MSC-mediated cancer cell kinetics, facilitating
      the development of future therapies. 

PMID- 24865967
TI  - PZR coordinates Shp2 Noonan and LEOPARD syndrome signaling in zebrafish and mice.
AB  - Noonan syndrome (NS) is an autosomal dominant disorder caused by activating
      mutations in the PTPN11 gene encoding Shp2, which manifests in congenital heart
      disease, short stature, and facial dysmorphia. The complexity of Shp2 signaling
      is exemplified by the observation that LEOPARD syndrome (LS) patients possess
      inactivating PTPN11 mutations yet exhibit similar symptoms to NS. Here, we
      identify "protein zero-related" (PZR), a transmembrane glycoprotein that
      interfaces with the extracellular matrix to promote cell migration, as a major
      hyper-tyrosyl-phosphorylated protein in mouse and zebrafish models of NS and LS.
      PZR hyper-tyrosyl phosphorylation is facilitated in a phosphatase-independent
      manner by enhanced Src recruitment to NS and LS Shp2. In zebrafish, PZR
      overexpression recapitulated NS and LS phenotypes. PZR was required for zebrafish
      gastrulation in a manner dependent upon PZR tyrosyl phosphorylation. Hence, we
      identify PZR as an NS and LS target. Enhanced PZR-mediated membrane recruitment
      of Shp2 serves as a common mechanism to direct overlapping pathophysiological
      characteristics of these PTPN11 mutations.

PMID- 24865970
TI  - A PEX7-centered perspective on the peroxisomal targeting signal type 2-mediated
      protein import pathway.
AB  - Peroxisomal matrix proteins are synthesized on cytosolic ribosomes and
      transported to the organelle by shuttling receptors. Matrix proteins containing a
      type 1 signal are carried to the peroxisome by PEX5, whereas those harboring a
      type 2 signal are transported by a PEX5-PEX7 complex. The pathway followed by
      PEX5 during the protein transport cycle has been characterized in detail. In
      contrast, not much is known regarding PEX7. In this work, we show that PEX7 is
      targeted to the peroxisome in a PEX5- and cargo-dependent manner, where it
      becomes resistant to exogenously added proteases. Entry of PEX7 and its cargo
      into the peroxisome occurs upstream of the first cytosolic ATP-dependent step of
      the PEX5-mediated import pathway, i.e., before monoubiquitination of PEX5. PEX7
      passing through the peroxisome becomes partially, if not completely, exposed to
      the peroxisome matrix milieu, suggesting that cargo release occurs at the trans
      side of the peroxisomal membrane. Finally, we found that export of peroxisomal
      PEX7 back into the cytosol requires export of PEX5 but, strikingly, the two
      export events are not strictly coupled, indicating that the two proteins leave
      the peroxisome separately.

PMID- 24865971
TI  - Histidine methylation of yeast ribosomal protein Rpl3p is required for proper 60S
      subunit assembly.
AB  - Histidine protein methylation is an unusual posttranslational modification. In
      the yeast Saccharomyces cerevisiae, the large ribosomal subunit protein Rpl3p is
      methylated at histidine 243, a residue that contacts the 25S rRNA near the P
      site. Rpl3p methylation is dependent upon the presence of Hpm1p, a candidate
      seven-beta-strand methyltransferase. In this study, we elucidated the biological
      activities of Hpm1p in vitro and in vivo. Amino acid analyses reveal that Hpm1p
      is responsible for all of the detectable protein histidine methylation in yeast.
      The modification is found on a polypeptide corresponding to the size of Rpl3p in
      ribosomes and in a nucleus-containing organelle fraction but was not detected in
      proteins of the ribosome-free cytosol fraction. In vitro assays demonstrate that
      Hpm1p has methyltransferase activity on ribosome-associated but not free Rpl3p,
      suggesting that its activity depends on interactions with ribosomal components.
      hpm1 null cells are defective in early rRNA processing, resulting in a deficiency
      of 60S subunits and translation initiation defects that are exacerbated in
      minimal medium. Cells lacking Hpm1p are resistant to cycloheximide and verrucarin
      A and have decreased translational fidelity. We propose that Hpm1p plays a role
      in the orchestration of the early assembly of the large ribosomal subunit and in
      faithful protein production.

PMID- 24865973
TI  - Superhydrophobic chips for cell spheroids high-throughput generation and drug
      screening.
AB  - We suggest the use of biomimetic superhydrophobic patterned chips produced by a
      benchtop methodology as low-cost and waste-free platforms for the production of
      arrays of cell spheroids/microtissues by the hanging drop methodology. Cell
      spheroids have a wide range of applications in biotechnology fields. For drug
      screening, they allow studying 3D models in structures resembling real living
      tissues/tumors. In tissue engineering, they are suggested as building blocks of
      bottom-up fabricated tissues. We used the wettability contrast of the chips to
      fix cell suspension droplets in the wettable regions and evaluated on-chip drug
      screening in 3D environment. Cell suspensions were patterned in the wettable
      spots by three distinct methods: (1) by pipetting the cell suspension directly in
      each individual spot, (2) by the continuous dragging of a cell suspension on the
      chip, and (3) by dipping the whole chip in a cell suspension. These methods
      allowed working with distinct throughputs and degrees of precision. The platforms
      were robust, and we were able to have static or dynamic environments in each
      droplet. The access to cell culture media for exchange or addition/removal of
      components was versatile and opened the possibility of using each spot of the
      chip as a mini-bioreactor. The platforms' design allowed for samples
      visualization and high-content image-based analysis on-chip. The combinatorial
      analysis capability of this technology was validated by following the effect of
      doxorubicin at different concentrations on spheroids formed using L929 and SaOs-2
      cells. 

PMID- 24865972
TI  - Mutations on the DNA binding surface of TBP discriminate between yeast TATA and
      TATA-less gene transcription.
AB  - Most RNA polymerase (Pol) II promoters lack a TATA element, yet nearly all Pol II
      transcription requires TATA binding protein (TBP). While the TBP-TATA interaction
      is critical for transcription at TATA-containing promoters, it has been unclear
      whether TBP sequence-specific DNA contacts are required for transcription at TATA
      less genes. Transcription factor IID (TFIID), the TBP-containing coactivator that
      functions at most TATA-less genes, recognizes short sequence-specific promoter
      elements in metazoans, but analogous promoter elements have not been identified
      in Saccharomyces cerevisiae. We generated a set of mutations in the yeast TBP DNA
      binding surface and found that most support growth of yeast. Both in vivo and in
      vitro, many of these mutations are specifically defective for transcription of
      two TATA-containing genes with only minor defects in transcription of two TATA
      less, TFIID-dependent genes. TBP binds several TATA-less promoters with apparent
      high affinity, but our results suggest that this binding is not important for
      transcription activity. Our results are consistent with the model that sequence
      specific TBP-DNA contacts are not important at yeast TATA-less genes and suggest
      that other general transcription factors or coactivator subunits are responsible
      for recognition of TATA-less promoters. Our results also explain why yeast TBP
      derivatives defective for TATA binding appear defective in activated
      transcription. 

PMID- 24865974
TI  - Biomarkers of CD4+ T-cell activation as risk factors for tuberculosis-associated
      immune reconstitution inflammatory syndrome.
AB  - OBJECTIVE: Patients coinfected with HIV and Mycobacterium tuberculosis frequently
      experience a paradoxical worsening of tuberculosis (TB) symptoms early after the
      initiation of combination antiretroviral therapy (cART). This immune
      reconstitution inflammatory syndrome (TB-IRIS) can lead to significant morbidity
      and needs to be distinguished from TB recurrence due to ineffective treatment. We
      investigated whether plasma biomarkers could predict the occurrence of TB-IRIS.
      DESIGN: ANRS 129 BKVIR is a single-arm multicentre trial that enrolled 69 cART
      naive HIV-1-infected patients treated for TB. The patients received once-daily
      tenofovir/emtricitabine/efavirenz first-line regimen. TB-IRIS cases (IRIS+) were
      validated by an Event Review Committee. METHODS: A panel of 26 plasma biomarkers
      was monitored longitudinally for 24 weeks from cART initiation onward, using
      multiplexed assays and high-sensitivity ELISA. Statistical analyses of biomarkers
      were adjusted for test multiplicity. RESULTS: One-third of patients (n=23)
      experienced TB-IRIS. The inflammatory cytokines and chemokines interleukin (IL)
      6, IL-8, interferon-gamma-induced protein 10 (IP-10), and tumour necrosis factor
      alpha (TNF-alpha) showed increased plasma levels at week 4 in IRIS-positive
      (IRIS+) patients (P<0.05 for each biomarker). The soluble IL-2 receptor sCD25,
      which is released upon CD4 T-cell activation, was significantly increased at week
      0 in IRIS+ patients (P<0.05), and remained elevated throughout follow-up. IL-7, a
      key homeostatic cytokine for CD4 T-cells, showed a trend for higher values in the
      TB-IRIS group. Both sCD25 and IL-7 baseline levels were independently associated
      with a shorter time to TB-IRIS occurrence (P=0.005 and P=0.02, respectively).
      CONCLUSION: These findings support a role for CD4 T-cell activation prior to
      massive inflammation in the development of TB-IRIS.

PMID- 24865975
TI  - Hypothermia attenuates apoptosis and protects contact between myelin basic
      protein-expressing oligodendroglial-lineage cells and neurons against hypoxia
      ischemia.
AB  - Periventricular leukomalacia (PVL) is a major form of brain injury among preterm
      infants, which is characterized by extensive loss and dysfunction of
      premyelinating oligodendrocytes (pre-OLs) induced by hypoxia-ischemia (HI).
      Therapeutic hypothermia, which is a standard treatment for term infants with HI
      encephalopathy, is not indicated for preterm infants because its safety and
      effect have not been established. Here we investigate the effectiveness and
      mechanism of hypothermia for the inhibition of pre-OLs damage in PVL. For in vivo
      studies, 6-day-old rats underwent left carotid artery ligation, followed by
      exposure to 6% oxygen for 1 hr under hypothermic or normothermic conditions. The
      loss of myelin basic protein (MBP) was inhibited by hypothermia. For in vitro
      studies, primary pre-OLs cultures were subjected to oxygen-glucose deprivation
      (OGD) under normothermic or hypothermic conditions, and dorsal root ganglion
      neurons were subsequently added. Hypothermia inhibited apoptosis of pre-OLs, and,
      despite specific downregulation of 21.5- and 17-kDa MBP mRNA expression during
      hypothermia, recovery of the expression after OGD was superior compared with
      normothermia. OGD caused disarrangement of MBP distribution, decreased the levels
      of phosphorylated 21.5-kDa MBP, and disturbed the capacity to contact with
      neurons, all of which were restored by hypothermia. Pharmacological inhibition of
      ERK1/2 phosphorylation with U0126 during and after OGD significantly reduced the
      protective effects of hypothermia on apoptosis and myelination, respectively.
      These data suggest that phosphorylated exon 2-containing (21.5- and possibly 17
      kDa) MBP isoforms may play critical roles in myelination and that hypothermia
      attenuates apoptosis and preserves the contact between OLs and neurons via ERK1/2
      phosphorylation.

PMID- 24865976
TI  - Hydrogels formed by enantioselective self-assembly of histidine-derived
      amphiphiles with tartaric acid.
AB  - Two chiral enantiomers of histidine-derived amphiphilic gelators, (4R,6S)-UIPCA
      and (4S,6R)-UIPCA, were synthesized through Pictet-Spengler reaction and their
      gelation behaviors with different organic acids were investigated. Interestingly,
      the chiral enantiomers of UIPCA showed smart enantioselectivity for gelating
      tartaric acid enantiomers to form hydrogels with excellent mechanical strength.
      The TEM and SEM images demonstrated that the hydrogels were composed of networks
      by physical entanglement of nanofibers with high aspect ratios. The formation of
      nanofibers was considered to be driven by the interplay of hydrogen bonding,
      electrostatic attraction, and hydrophobic interaction, which was supported by XRD
      and FT-IR spectra. The hydrogels exhibited sensitive response to a series of
      external stimuli, such as temperature, metal ions, and host-guest interactions,
      to realize the reversible gel-sol transition. The property of the gelation was
      elaborated and the gelators were expected to find their applications in chiral
      discrimination. 

PMID- 24865977
TI  - Regionalized LCA-based optimization of building energy supply: method and case
      study for a Swiss municipality.
AB  - This paper presents a regionalized LCA-based multiobjective optimization model of
      building energy demand and supply for the case of a Swiss municipality for the
      minimization of greenhouse gas emissions and particulate matter formation. The
      results show that the environmental improvement potential is very large: in the
      optimal case, greenhouse gas emissions from energy supply could be reduced by
      more than 75% and particulate emissions by over 50% in the municipality. This
      scenario supposes a drastic shift of heat supply systems from a fossil fuel
      dominated portfolio to a portfolio consisting of mainly heat pump and woodchip
      incineration systems. In addition to a change in heat supply technologies, roofs,
      windows and walls would need to be refurbished in more than 65% of the
      municipality's buildings. The full potential of the environmental impact
      reductions will hardly be achieved in reality, particularly in the short term,
      for example, because of financial constraints and social acceptance, which were
      not taken into account in this study. Nevertheless, the results of the
      optimization model can help policy makers to identify the most effective measures
      for improvement at the decision making level, for example, at the building level
      for refurbishment and selection of heating systems or at the municipal level for
      designing district heating networks. Therefore, this work represents a starting
      point for designing effective incentives to reduce the environmental impact of
      buildings. While the results of the optimization model are specific to the
      municipality studied, the model could readily be adapted to other regions. 

PMID- 24865978
TI  - The effect of pre-treatment with transcutaneous electrical acupoint stimulation
      on the quality of recovery after ambulatory breast surgery: a prospective,
      randomised controlled trial.
AB  - Electroacupuncture has been demonstrated to be effective at alleviating pain and
      postoperative side-effects. Our aim was to investigate whether transcutaneous
      electric acupoint stimulation, a low-skill alternative to needle-based
      electroacupuncture, could improve the quality of recovery after ambulatory
      surgery. Seventy-two women scheduled for cosmetic breast surgery were randomly
      allocated to transcutaneous electric acupoint stimulation or sham groups.
      Patients in the transcutaneous electric acupoint stimulation group received 30
      min of electrical stimulation at three acupoints located on the hand and forearm
      before the induction of general anaesthesia. We found significant mean (SD)
      differences between the transcutaneous electric acupoint stimulation and sham
      groups in the mean (SD) length of recovery room stay (35.6 (12.9) min vs 48.3
      (16.3) min, p = 0.01), time to removal of the laryngeal mask airway (10.2 (2.5)
      min vs 17.8 (4.4) min, p = 0.01), and time to reorientation of the patient (14.6
      (3.2) min vs 26.5 (5.0) min, p = 0.01). Further, postoperative pain scores and
      the incidence of side-effects were all lower in the transcutaneous electric
      acupoint stimulation group. In conclusion, transcutaneous electric acupoint
      stimulation can significantly improve the quality of recovery and decrease the
      incidence of anaesthesia-related side-effects for patients undergoing ambulatory
      surgery.

PMID- 24865979
TI  - The impact of land abandonment on species richness and abundance in the
      Mediterranean Basin: a meta-analysis.
AB  - Land abandonment is common in the Mediterranean Basin, a global biodiversity
      hotspot, but little is known about its impacts on biodiversity. To upscale
      existing case-study insights to the Pan-Mediterranean level, we conducted a meta
      analysis of the effects of land abandonment on plant and animal species richness
      and abundance in agroforestry, arable land, pastures, and permanent crops of the
      Mediterranean Basin. In particular, we investigated (1) which taxonomic groups
      (arthropods, birds, lichen, vascular plants) are more affected by land
      abandonment; (2) at which spatial and temporal scales the effect of land
      abandonment on species richness and abundance is pronounced; (3) whether previous
      land use and current protected area status affect the magnitude of changes in the
      number and abundance of species; and (4) how prevailing landforms and climate
      modify the impacts of land abandonment. After identifying 1240 potential studies,
      154 cases from 51 studies that offered comparisons of species richness and
      abundance and had results relevant to our four areas of investigation were
      selected for meta-analysis. Results are that land abandonment showed slightly
      increased (effect size  = 0.2109, P<0.0001) plant and animal species richness and
      abundance overall, though results were heterogeneous, with differences in effect
      size between taxa, spatial-temporal scales, land uses, landforms, and climate. In
      conclusion, there is no "one-size-fits-all" conservation approach that applies to
      the diverse contexts of land abandonment in the Mediterranean Basin. Instead,
      conservation policies should strive to increase awareness of this heterogeneity
      and the potential trade-offs after abandonment. The strong role of factors at the
      farm and landscape scales that was revealed by the analysis indicates that
      purposeful management at these scales can have a powerful impact on biodiversity.

PMID- 24865982
TI  - Etiology of the membrane potential of rat white fat adipocytes.
AB  - The plasma membrane potential (Vm) is key to many physiological processes;
      however, its ionic etiology in white fat adipocytes is poorly characterized. To
      address this question, we employed the perforated patch current clamp and cell
      attached patch clamp methods in isolated primary white fat adipocytes and their
      cellular model 3T3-L1. The resting Vm of primary and 3T3-L1 adipocytes were -32.1
      +/- 1.2 mV (n = 95) and -28.8 +/- 1.2 mV (n = 87), respectively. Vm was
      independent of cell size and fat content. Elevation of extracellular K(+) to 50
      mM by equimolar substitution of bath Na(+) did not affect Vm, whereas
      substitution of bath Na(+) with the membrane-impermeant cation N-methyl-D
      glucamine(+)-hyperpolarized Vm by 16 mV, data indicative of a nonselective cation
      permeability. Substitution of 133 mM extracellular Cl(-) with gluconate
      depolarized Vm by 25 mV, whereas Cl(-) substitution with I(-) caused a -9 mV
      hyperpolarization. Isoprenaline (10 MUM), but not insulin (100 nM), significantly
      depolarized Vm. Single-channel ion activity was voltage independent; currents
      were indicative for Cl(-) with an inward slope conductance of 16 +/- 1.3 pS (n =
      11) and a reversal potential close to the Cl(-) equilibrium potential, -29 +/-
      1.6 mV. Although the reduction of extracellular Cl(-) elevated the intracellular
      Ca(2+) of adipocytes, this was not as large as that produced by elevation of
      extracellular K(+). In conclusion, the Vm of white fat adipocytes is well
      described by the Goldman-Hodgkin-Katz equation with a predominant permeability to
      Cl(-), where its biophysical and single-channel properties suggest a volume
      sensitive anion channel identity. Consequently, changes in serum Cl(-)
      homeostasis or the adipocyte's permeability to this anion via drugs will affect
      its Vm, intracellular Ca(2+), and ultimately its function and its role in
      metabolic control.

PMID- 24865981
TI  - Hepatic glucose uptake and disposition during short-term high-fat vs. high
      fructose feeding.
AB  - In dogs consuming a high-fat and -fructose diet (52 and 17% of total energy,
      respectively) for 4 wk, hepatic glucose uptake (HGU) in response to
      hyperinsulinemia, hyperglycemia, and portal glucose delivery is markedly blunted
      with reduction in glucokinase (GK) protein and glycogen synthase (GS) activity.
      The present study compared the impact of selective increases in dietary fat and
      fructose on liver glucose metabolism. Dogs consumed weight-maintaining chow (CTR)
      or hypercaloric high-fat (HFA) or high-fructose (HFR) diets diet for 4 wk before
      undergoing clamp studies with infusion of somatostatin and intraportal insulin (3
      4 times basal) and glucagon (basal). The hepatic glucose load (HGL) was doubled
      during the clamp using peripheral vein (Pe) glucose infusion in the first 90 min
      (P1) and portal vein (4 mg.kg(-1).min(-1)) plus Pe glucose infusion during the
      final 90 min (P2). During P2, HGU was 2.8 +/- 0.2, 1.0 +/- 0.2, and 0.8 +/- 0.2
      mg.kg(-1).min(-1) in CTR, HFA, and HFR, respectively (P < 0.05 for HFA and HFR
      vs. CTR). Compared with CTR, hepatic GK protein and catalytic activity were
      reduced (P < 0.05) 35 and 56%, respectively, in HFA, and 53 and 74%,
      respectively, in HFR. Liver glycogen concentrations were 20 and 38% lower in HFA
      and HFR than CTR (P < 0.05). Hepatic Akt phosphorylation was decreased (P < 0.05)
      in HFA (21%) but not HFR. Thus, HFR impaired hepatic GK and glycogen more than
      HFA, whereas HFA reduced insulin signaling more than HFR. HFA and HFR effects
      were not additive, suggesting that they act via the same mechanism or their
      effects converge at a saturable step. 

PMID- 24865984
TI  - A methodological quality synthesis of systematic reviews on computer-mediated
      continuing education for healthcare providers.
AB  - BACKGROUND: Healthcare providers use continuing education (CE) to meet
      professional development requirements and to ensure optimal patient care. There
      has been a dramatic increase in computer-mediated CE (CMCE) programs. AIMS: To
      synthesize the literature regarding the current state of the science on the
      efficacy of CMCE for healthcare professionals, particularly as it relates to
      provider learning and patient outcomes. Specifically, this review assesses the
      methodological quality of existing systematic reviews and meta-analyses. METHODS:
      A literature search was conducted using Cochrane Library, PubMed, and CINAHL.
      Review articles evaluating the efficacy of CMCE for healthcare providers were
      included. Publications were searched between 2002 and 2013 and limited to those
      printed in English. An objective measurement tool, AMSTAR, was used to assess the
      methodological quality of each review. AMSTAR is an 11-item instrument, in which
      individual criteria were evaluated and a composite score of all 11 components was
      determined for each review. Outcomes of each review were also categorized based
      on Kirkpatrick's levels for summative evaluation: (i) Learner satisfaction, (ii)
      Learning outcomes, (iii) Performance improvement, (iv) Patient/health outcomes.
      RESULTS: Starting with 231 articles, 11 met the inclusion criteria for this
      evaluation. AMSTAR quality scores of the reviews ranged from 7 to 11, with 11
      indicating the strongest quality. Although weak research design of many studies
      and heterogeneous topics covered make summative evaluations difficult, there were
      some common themes covered in the articles reviewed. Healthcare providers were
      largely satisfied with using CMCE programs. Overall, the studies comparing CMCE
      to traditional CE methods found the impact on learning outcomes to be comparable,
      with neither method necessarily superior. Additionally, all reviews lacked
      evaluation of practice outcomes. LINKING EVIDENCE TO ACTION: While results of
      this review show promise for CMCE, further evaluation and more rigorously
      conducted research is necessary. Particular focus is needed to determine the
      effects of CMCE on health outcomes.

PMID- 24865980
TI  - Bone substitutes in orthopaedic surgery: from basic science to clinical practice.
AB  - Bone substitutes are being increasingly used in surgery as over two millions bone
      grafting procedures are performed worldwide per year. Autografts still represent
      the gold standard for bone substitution, though the morbidity and the inherent
      limited availability are the main limitations. Allografts, i.e. banked bone, are
      osteoconductive and weakly osteoinductive, though there are still concerns about
      the residual infective risks, costs and donor availability issues. As an
      alternative, xenograft substitutes are cheap, but their use provided contrasting
      results, so far. Ceramic-based synthetic bone substitutes are alternatively based
      on hydroxyapatite (HA) and tricalcium phosphates, and are widely used in the
      clinical practice. Indeed, despite being completely resorbable and weaker than
      cortical bone, they have exhaustively proved to be effective. Biomimetic HAs are
      the evolution of traditional HA and contains ions (carbonates, Si, Sr, Fl, Mg)
      that mimic natural HA (biomimetic HA). Injectable cements represent another
      evolution, enabling mininvasive techniques. Bone morphogenetic proteins (namely
      BMP2 and 7) are the only bone inducing growth factors approved for human use in
      spine surgery and for the treatment of tibial nonunion. Demineralized bone matrix
      and platelet rich plasma did not prove to be effective and their use as bone
      substitutes remains controversial. Experimental cell-based approaches are
      considered the best suitable emerging strategies in several regenerative medicine
      application, including bone regeneration. In some cases, cells have been used as
      bioactive vehicles delivering osteoinductive genes locally to achieve bone
      regeneration. In particular, mesenchymal stem cells have been widely exploited
      for this purpose, being multipotent cells capable of efficient osteogenic
      potential. Here we intend to review and update the alternative available
      techniques used for bone fusion, along with some hints on the advancements
      achieved through the experimental research in this field. 

PMID- 24865985
TI  - Acquisition of ephemeral module in roots: a new view and test.
AB  - The terminal root branch orders composed mainly of primarily-developed tissues
      are increasingly recognized as an ephemeral module specialized for resource
      absorption. This root module is crucial in driving a range of ecosystem processes
      such as belowground productivity, carbon and nutrient cycling. Traditionally,
      acquisition of the ephemeral root module is achieved by separating these
      primarily-developed branch orders with forceps. However, obtaining this root
      segment with forceps approach is labor-intensive which may not be applicable for
      studies with an appreciable amount of root samples. To address this challenge, we
      developed a new idea to obtain the ephemeral root module. In this new view, root
      samples were tenderly kneaded by hand and the detached roots are considered as
      the ephemeral root module. To test this idea, four species with contrasting
      growing environment were selected and a range of chemicals were determined
      including C, N, P, Ca, S, Mg, Ba, Zn, Mn, Pb, Cu, V and Li. We found no or little
      difference of these chemicals in roots by hand-kneading approach from roots by
      forceps approach. These results suggested that hand-kneading method could be a
      convenient way to acquire ephemeral root module. 

PMID- 24865983
TI  - Impairments of hepatic gluconeogenesis and ketogenesis in PPARalpha-deficient
      neonatal mice.
AB  - Peroxisome proliferator activated receptor-alpha (PPARalpha) is a master
      transcriptional regulator of hepatic metabolism and mediates the adaptive
      response to fasting. Here, we demonstrate the roles for PPARalpha in hepatic
      metabolic adaptations to birth. Like fasting, nutrient supply is abruptly altered
      at birth when a transplacental source of carbohydrates is replaced by a high-fat,
      low-carbohydrate milk diet. PPARalpha-knockout (KO) neonatal mice exhibit
      relative hypoglycemia due to impaired conversion of glycerol to glucose. Although
      hepatic expression of fatty acyl-CoA dehydrogenases is imparied in PPARalpha
      neonates, these animals exhibit normal blood acylcarnitine profiles. Furthermore,
      quantitative metabolic fate mapping of the medium-chain fatty acid
      [(13)C]octanoate in neonatal mouse livers revealed normal contribution of this
      fatty acid to the hepatic TCA cycle. Interestingly, octanoate-derived carbon
      labeled glucose uniquely in livers of PPARalpha-KO neonates. Relative
      hypoketonemia in newborn PPARalpha-KO animals could be mechanistically linked to
      a 50% decrease in de novo hepatic ketogenesis from labeled octanoate. Decreased
      ketogenesis was associated with diminished mRNA and protein abundance of the fate
      committing ketogenic enzyme mitochondrial 3-hydroxymethylglutaryl-CoA synthase
      (HMGCS2) and decreased protein abundance of the ketogenic enzyme beta
      hydroxybutyrate dehydrogenase 1 (BDH1). Finally, hepatic triglyceride and free
      fatty acid concentrations were increased 6.9- and 2.7-fold, respectively, in
      suckling PPARalpha-KO neonates. Together, these findings indicate a primary
      defect of gluconeogenesis from glycerol and an important role for PPARalpha
      dependent ketogenesis in the disposal of hepatic fatty acids during the neonatal
      period. 

PMID- 24865986
TI  - Can telemonitoring reduce hospitalization and cost of care? A health plan's
      experience in managing patients with heart failure.
AB  - Telemonitoring provides a potentially useful tool for disease and case management
      of those patients who are likely to benefit from frequent and regular monitoring
      by health care providers. Since 2008, Geisinger Health Plan (GHP) has implemented
      a telemonitoring program that specifically targets those members with heart
      failure. This study assesses the impact of this telemonitoring program by
      examining claims data of those GHP Medicare Advantage plan members who were
      enrolled in the program, measuring its impact in terms of all-cause hospital
      admission rates, readmission rates, and total cost of care. The results indicate
      significant reductions in probability of all-cause admission (odds ratio [OR]
      0.77; P<0.01), 30-day and 90-day readmission (OR 0.56, 0.62; P<0.05), and cost of
      care (11.3%; P<0.05). The estimated return on investment was 3.3. These findings
      imply that telemonitoring can be an effective add-on tool for managing elderly
      patients with heart failure.

PMID- 24865987
TI  - Time-resolved fluorescence spectroscopy study of excited state dynamics of alkyl-
      and benzo-substituted triphyrin(2.1.1).
AB  - We have investigated the photophysical properties of alkyl-substituted
      triphyrin(2.1.1) (ATp) and benzotriphyrin(2.1.1) (BTp) by steady-state and time
      resolved fluorescence spectroscopy. We focused on the effect of NH proton
      tautomerization, planarity of the macrocycles, and substituents on these
      properties. The fluorescence quantum yields (Phiy) of ATp did not depend on
      solvent viscosity, whereas those of BTp increased with solvent viscosity,
      reaching a maximum value of 0.17 in paraffin. Interestingly, analyzing Phiy
      showed that the non-radiative rate constant of BTp decreased sharply as the
      solvent viscosity increased. These results suggest that the substituted phenyl
      groups play a crucial role in suppressing molecular distortion, thus leading to
      decreased non-radiative relaxation in triphyrin(2.1.1). The hydrogen bond formed
      in the inner cavity potentially contributes to the suppression of the structural
      distortion, whereas the pyrrole rings in the macrocycle are close, as in
      porphycene. 

PMID- 24865988
TI  - Genetic variants associated with susceptibility of Ashkenazi Jews to West Nile
      virus infection.
AB  - The epidemiology of West Nile virus (WNV) in Israel is different from other
      neighbouring countries in the Middle East where disease burden has been minimal.
      We analysed a cohort of Ashkenazi Jewish patients with symptomatic WNV infection
      (n = 39), and WNV-negative controls (n = 61), for nine genetic variants that has
      been suggested to be associated with susceptibility to WNV. Two single nucleotide
      polymorphisms were significantly more frequent in WNV-infected than non-infected
      individuals, rs7280422 (MX1) [odds ratio (OR) 4.05, 95% confidence interval (CI)
      2.04-8.03, P < 0.001] and rs3213545 (OASL) (OR 1.85, 95% CI 1.03-3.3, P = 0.03).
      Genetic polymorphism may play a significant role in susceptibility to WNV
      infection in Ashkenazi Jews.

PMID- 24865989
TI  - A nano-frost array technique to prepare nanoporous PVDF membranes.
AB  - Frost, the solid deposition of water vapor from humid air, forms on the surface
      of a solid substrate when its temperature drops below the freezing point of
      water. In this study, we demonstrate how this natural phenomenon can be applied
      to develop novel nanoporous materials. The solvent annealing of polyvinylidene
      fluoride (PVDF) infiltrated into nanopores induced template-directed dewetting
      thus preparing nanoembossing films. Then, water nanodroplets formed on the cold
      polymer nanopatterned surfaces following the embossing patterns, similar to dew
      formation on the ground. Subsequently, the nanodroplets were frozen and then
      removed by freeze-drying. This nano-frost array technique produced nanoporous
      PVDF membranes with an average thickness of 250 (+/- 48) nm. It was revealed that
      the nanopatterned surface formed by solvent annealing played an important role in
      achieving a nano-frost array with an adjustable size. Additionally, the freezing
      process led to significant changes of the PVDF crystallinity and polymorphism.
      Our results prove that the nano-frost array technique can be broadly used to
      design ordered nanoporous structures and provide new prospects in nanomaterial
      fields.

PMID- 24865990
TI  - Efficient strategy for maintaining and enhancing the huperzine A production of
      Shiraia sp. Slf14 through inducer elicitation.
AB  - Huperzine A (HupA), a naturally occurring lycopodium alkaloid, is a potent,
      highly specific and reversible inhibitor of acetylcholinesterase and is a
      potential treatment for Alzheimer's disease. However, isolating HupA from
      Huperziaceae plants is inefficient; thus, extracting this compound from
      endophytic fungi may be more controllable and sustainable. However, the large
      scale production of this chemical from endophytes is limited by the innate
      instability of endophytic fungi. In this study, we maintained the stability and
      viability of the HupA-producing endophytic fungus Shiraia sp. Slf14 and enhanced
      the HupA titers during fermentation by adding Huperzia serrata extracts (HSE), L
      lysine, and acetic acid into the culture as inducers. Adding trace amounts of
      HupA clearly improved the HupA production of Shiraia sp. Slf14, reaching a
      maximum content of approximately 40 MUg g(-1). Moreover, the addition of HSE and
      L-lysine promoted HupA production in the flask fermentation. The aforementioned
      bioprocessing strategy may be potentially applied to other endophytic fungal
      culture systems for the efficient production of plant secondary metabolites. 

PMID- 24865991
TI  - Serum microRNA-21 as a diagnostic marker for lung carcinoma: a systematic review
      and meta-analysis.
AB  - OBJECTIVES: MicroRNA-21 in serum is a promising marker for the diagnosis of lung
      carcinoma. A meta-analysis was performed to assess the diagnostic accuracy and
      clinical value of serum microRNA-21 in patients with lung carcinoma. METHODS:
      PubMed, EMBASE, Web of Knowledge (ISI), the Cochrane Library, Scopus, BioMed
      Central, Science Direct, China National Knowledge Infrastructure (CNKI), Wan Fang
      data and Technology of Chongqing (VIP) databases were searched to identify
      studies in English and Chinese that assessed the diagnostic value of serum miR-21
      for lung carcinoma, from inception to 9 April 2014. Two independent investigators
      identified and extracted the study characteristics from all articles according to
      defined inclusion and exclusion criteria. Quality assessment of diagnostic
      accuracy studies (QUADAS) was used to score the quality of the eligible studies.
      Stata12 and Meta-DiSc software were used to test the heterogeneity and to perform
      the meta-analysis. RESULTS: Our search returned 1008 articles, of which seven
      fulfilled the inclusion criteria, accounting for 500 patients and 386 controls.
      Using random-effect model analysis, the summary assessments revealed that the
      mean sensitivity was 0.71% (95%CI: 57-82%) and specificity was 0.84% (95%CI: 76
      89%). The area under the receiver operating characteristic curve was 0.86 (95%CI:
      0.83-0.89). In addition, heterogeneity was clearly apparent but was not caused by
      the threshold effect, as shown by Meta-DiSc analysis. CONCLUSION: The current
      evidence suggests that serum miR-21 can be rapidly measured in lung carcinoma
      patients and has potential diagnostic value with moderate sensitivity and
      specificity. Further prospective studies to assess the early stage diagnostic
      value are needed in the future.

PMID- 24865992
TI  - Ecological constraints on sensory systems: compound eye size in Daphnia is
      reduced by resource limitation.
AB  - Eye size is an indicator of visual capability, and macroevolutionary patterns
      reveal that taxa inhabiting dim environments have larger eyes than taxa from
      bright environments. This suggests that the light environment is a key driver of
      variation in eye size. Yet other factors not directly linked with visual tasks
      (i.e., non-sensory factors) may influence eye size. We sought to jointly
      investigate the roles of sensory (light) and non-sensory factors (food) in
      determining eye size and ask whether non-sensory factors could constrain visual
      capabilities. We tested environmental influences on eye size in four species of
      the freshwater crustacean Daphnia, crossing bright and dim light levels with high
      and low resource levels. We measured absolute eye size and eye size relative to
      body size in early and late adulthood. In general, Daphnia reared on low
      resources had smaller eyes, both absolutely and relatively. In contrast to the
      dominant macroevolutionary pattern, phenotypic plasticity in response to light
      was rarely significant. These patterns of phenotypic plasticity were true for
      overall diameter of the eye and the diameter of individual facets. We conclude
      that non-sensory environmental factors can influence sensory systems, and in
      particular, that resource availability may be an important constraint on visual
      capability. 

PMID- 24865994
TI  - The Environment of care model: a paradigm shift in comprehensive breast care.
AB  - The delivery of comprehensive breast care seems to be undergoing a paradigm shift
      driven by advances in technology, interprofessional collaboration and patient
      dissatisfaction with interruptions in care. This paradigm shift includes the
      emergence of new models of care that optimize the use of embedded radiology
      services and encourage greater interprofessional collaboration. This paper
      briefly reviews the three drivers (advances in technology, expectations regarding
      interprofessional collaboration and patient dissatisfaction with interrupted
      care) underlying the paradigm shift in comprehensive breast care as well as
      introduces the environment of care model, which describes the proximity of
      radiology services and interprofessional collaboration between the Women's
      Wellness Clinic (WWC) and Radiology at the Karmanos Cancer Institute (KCI) - both
      based in the United States. In addition, this model is proposed as a way to
      facilitate improved patient satisfaction and early appropriate referral. Finally,
      plans for evaluating the effectiveness of this model are presented.

PMID- 24865993
TI  - The development of clinical reasoning and interprofessional behaviors: service
      learning at a student-run free clinic.
AB  - This article examines the benefits of a student run free clinic (SRFC) as a
      service learning experience for students in medicine, pharmacy, occupational
      therapy, physical therapy and physician assistant programs. We hypothesized that
      students who participate in an interprofessional service learning course and
      volunteer at a SRFC would demonstrate significant increases in perceptions and
      attitudes for working in interprofessional health care teams and clinical
      reasoning skills compared to students who did not participate. Three assessments
      were administered to an experimental and control group of pre-clinical students
      from medical, occupational therapy, physical therapy, pharmacy and physician
      assistant programs before and after participation in an interprofessional service
      learning course and volunteering at the SRFC. The tools were the
      Interdisciplinary Education Perception Scale (IEPS), Readiness for
      Interprofessional Learning Scale (RIPLS) and the Self-Assessment of Clinical
      Reflection and Reasoning (SACRR). Students who completed the course had
      improvements in interprofessional perceptions and attitudes (p = 0.03) and
      perceptions of clinical reasoning skills when compared to the control group (p =
      0.002). This study is novel as it examined students' perceptions of
      interprofessional attitudes and clinical reasoning following participation in an
      interprofessional service-learning course and participation in a SRFC.

PMID- 24865995
TI  - Fostering a "common culture"? Responses to the Francis Inquiry demonstrate the
      need for an interprofessional response.

PMID- 24865996
TI  - Mapping brain glucose uptake with chemical exchange-sensitive spin-lock magnetic
      resonance imaging.
AB  - Uptake of administered D-glucose (Glc) or 2-deoxy-D-glucose (2DG) has been
      indirectly mapped through the chemical exchange (CE) between glucose hydroxyl and
      water protons using CE-dependent saturation transfer (glucoCEST) magnetic
      resonance imaging (MRI). We propose an alternative technique-on-resonance CE
      sensitive spin-lock (CESL) MRI-to enhance responses to glucose changes. Phantom
      data and simulations suggest higher sensitivity for this 'glucoCESL' technique
      (versus glucoCEST) in the intermediate CE regime relevant to glucose. Simulations
      of CESL signals also show insensitivity to B0-fluctuations. Several findings are
      apparent from in vivo glucoCESL studies of rat brain at 9.4 Tesla with
      intravenous injections. First, dose-dependent responses are nearly linearly for
      0.25-, 0.5-, and 1-g/kg Glc administration (obtained with 12-second temporal
      resolution), with changes robustly detected for all doses. Second, responses at a
      matched dose of 1 g/kg are much larger and persist for a longer duration for 2DG
      versus Glc administration, and are minimal for mannitol as an osmolality control.
      And third, with similar increases in steady-state blood glucose levels, glucoCESL
      responses are ~2.2 times higher for 2DG versus Glc, consistent with their
      different metabolic properties. Overall, we show that glucoCESL MRI could be a
      highly sensitive and quantifiable tool for glucose transport and metabolism
      studies. 

PMID- 24865997
TI  - Ablation of MMP9 gene ameliorates paracellular permeability and fibrinogen
      amyloid beta complex formation during hyperhomocysteinemia.
AB  - Increased blood level of homocysteine (Hcy), called hyperhomocysteinemia (HHcy)
      accompanies many cognitive disorders including Alzheimer's disease. We
      hypothesized that HHcy-enhanced cerebrovascular permeability occurs via
      activation of matrix metalloproteinase-9 (MMP9) and leads to an increased
      formation of fibrinogen-beta-amyloid (Fg-Abeta) complex. Cerebrovascular
      permeability changes were assessed in C57BL/6J (wild type, WT), cystathionine
      beta-synthase heterozygote (Cbs+/-, a genetic model of HHcy), MMP9 gene knockout
      (Mmp9-/-), and Cbs and Mmp9 double knockout (Cbs+/-/Mmp9-/-) mice using a dual
      tracer probing method. Expression of vascular endothelial cadherin (VE-cadherin)
      and Fg-Abeta complex formation was assessed in mouse brain cryosections by
      immunohistochemistry. Short-term memory of mice was assessed with a novel object
      recognition test. The cerebrovascular permeability in Cbs+/- mice was increased
      via mainly the paracellular transport pathway. VE-cadherin expression was the
      lowest and Fg-Abeta complex formation was the highest along with the diminished
      short-term memory in Cbs+/- mice. These effects of HHcy were ameliorated in Cbs+/
      /Mmp9-/- mice. Thus, HHcy causes activation of MMP9 increasing cerebrovascular
      permeability by downregulation of VE-cadherin resulting in an enhanced formation
      of Fg-Abeta complex that can be associated with loss of memory. These data may
      lead to the identification of new targets for therapeutic intervention that can
      modulate HHcy-induced cerebrovascular permeability and resultant pathologies. 

PMID- 24865998
TI  - Role of spleen-derived monocytes/macrophages in acute ischemic brain injury.
AB  - Monocytes/macrophages (MMs), mononuclear phagocytes, have been implicated in
      stroke-induced inflammation and injury. However, the presence of pro-inflammatory
      Ly-6C(high) and antiinflammatory Ly-6C(low) monocyte subsets raises uncertainty
      regarding their role in stroke pathologic assessment. With recent identification
      of the spleen as an immediate reservoir of MMs, this current study addresses
      whether the spleen-derived MMs are required for stroke pathologic assessment. We
      observed that the spleen was contracted in poststroke animals and the contraction
      was accompanied by decreased number of Ly-6C(high) and Ly-6C(low) subsets in the
      spleen. The deployment of these subsets from the spleen temporally coincided with
      respective increases in the ischemic brain. Compared to mice with the spleen,
      mice receiving a splenectomy just before the stroke displayed less accumulation
      of Ly-6C(high) and Ly-6C(low) MMs in the brain. Despite the reduced accumulation
      of both subsets, infarct size and swelling were not reduced in the asplenic mice.
      The dissociative findings of infarct size and extent of MM infiltration in the
      postischemic brain indicate minimal involvement of spleen-derived total MMs in
      acute infarct development. Selective Ly-6C(high) or Ly-6C(low) MM targeting is
      suggested to address the contribution of the individual subset to acute stroke
      pathologic assessment. 

PMID- 24865999
TI  - CO2 has no therapeutic effect on early microvasospasm after experimental
      subarachnoid hemorrhage.
AB  - In addition to delayed vasospasm also early brain injury, which occurs during the
      first few days after subarachnoid hemorrhage (SAH) when large cerebral arteries
      are still fully functional, plays an important role for the outcome after SAH. In
      the current study, we investigated the hypothesis that carbon dioxide (CO2), a
      strong cerebral vasodilator, has a therapeutic potential against early
      posthemorrhagic microvasospasm. C57BL/6 mice (n=36) and Sprague-Dawley rats
      (n=23) were subjected to sham surgery or SAH by filament perforation. The pial
      microcirculation in the mice was visualized 3 and 24 hours after SAH using
      intravital fluorescence microscopy. Partial pressure of CO2 (PaCO2) was modulated
      by hyper- or hypoventilation or by inhalation of 10% CO2. In rats, CO2-mediated
      changes in cerebral blood flow (CBF) were measured at the same time points using
      laser Doppler fluxmetry. Increased PaCO2 caused vasodilatation in sham-operated
      animals. Following SAH, however, cerebral arterioles were nonreactive to CO2.
      This lack of microvascular CO2 reactivity was accompanied by a complete loss of
      CO2-induced hyperemia. Our data show that CO2 is not able to dilate spastic
      microvessels and to increase CBF early after SAH. Future therapeutic approaches
      will therefore need to address mechanisms beyond CO2. 

PMID- 24866001
TI  - Primate polemic: commentary on Smith, Couchman, and Beran (2014).
AB  - Smith, Couchman, and Beran (2014, pp. 115-131) take issue with recent attempts to
      account for so-called metacognitive behavior in nonhuman animals in terms of
      simple processes of associative reinforcement learning. Their arguments rely on
      appeals to unconvincing and equivocal empirical evidence, and a misrepresentation
      of the nature of associative learning. Although the existing data do not rule out
      the possibility that animals possess "true" metacognitive abilities, neither do
      they currently mandate this conclusion. The suggestion that simple mechanisms
      might give rise to complex behaviors ties in with recent attempts in cognitive
      and social psychology, and behavioral neuroscience, to explain human behavior in
      terms of similar, simple mechanisms. As such this perspective should be seen as
      an opportunity for comparative psychology, not a threat.

PMID- 24866000
TI  - Protein flexibility facilitates quaternary structure assembly and evolution.
AB  - The intrinsic flexibility of proteins allows them to undergo large conformational
      fluctuations in solution or upon interaction with other molecules. Proteins also
      commonly assemble into complexes with diverse quaternary structure arrangements.
      Here we investigate how the flexibility of individual protein chains influences
      the assembly and evolution of protein complexes. We find that flexibility appears
      to be particularly conducive to the formation of heterologous (i.e., asymmetric)
      intersubunit interfaces. This leads to a strong association between subunit
      flexibility and homomeric complexes with cyclic and asymmetric quaternary
      structure topologies. Similarly, we also observe that the more nonhomologous
      subunits that assemble together within a complex, the more flexible those
      subunits tend to be. Importantly, these findings suggest that subunit flexibility
      should be closely related to the evolutionary history of a complex. We confirm
      this by showing that evolutionarily more recent subunits are generally more
      flexible than evolutionarily older subunits. Finally, we investigate the very
      different explorations of quaternary structure space that have occurred in
      different evolutionary lineages. In particular, the increased flexibility of
      eukaryotic proteins appears to enable the assembly of heteromeric complexes with
      more unique components. 

PMID- 24866002
TI  - Metacognition as discrimination: commentary on Smith et al. (2014).
AB  - Smith, Couchman, and Beran (2014, pp. 115-131) critique recent "low-level"
      associative process models of nonhuman metacognition. We agree with many aspects
      of their critique. However, the alternative account they offer may not help
      specify the mechanisms of metacognition. We propose a middle-ground approach,
      based on the methods of comparative psychophysics, by which metacognition is
      treated as a discrimination problem.

PMID- 24866003
TI  - Two concepts of metacognition.
AB  - This comment distinguishes two concepts of metacognition that are often conflated
      by Smith, Couchman, and Beran (2014, pp. 115-131). Animal metacognition: A tale
      of two comparative psychologies. Journal of Comparative Psychology. One refers to
      any executively controlled process, the other to metarepresentational processes.
      It is argued that more progress will be made by comparative researchers if they
      target their investigations separately at these two phenomena, as well as
      studying the relationships between them.

PMID- 24866005
TI  - Metacognition does not imply self-reflection, but it does imply function.
AB  - Is self-reflection necessary for metacognition to occur? Like Kornell (2014, pp.
      143-149), we struggle with this question. If humans metacognition is not always
      self-reflective, why should we expect animals to be so? We suggest that one way
      to pursue metacognition in animals is to examine its ecological and evolutionary
      relevance.

PMID- 24866006
TI  - Where is the skepticism in animal metacognition?
AB  - The comparative analysis of metacognition may answer fundamental questions about
      the evolution of cognition. Although a substantial amount of research has been
      directed toward this goal in the last two decades, the recent development of
      quantitative nonmetacognition models has raised questions about the existence of
      metacognition in nonhumans. Kornell (2014, pp. 143-149) proposes that advances in
      animal metacognition may be made by following emerging trends in human
      metacognition research, namely that animal metacognition may take the form of
      drawing inferences from metacognitive cues without directly assessing the
      strength of memories. A problem with this approach is noted. Because the
      metacognitive status of certainty judgments in animals is at the center of the
      dispute in the field, demonstrations of the inferential view would not provide
      evidence that putative metacognitive cues are indeed based on metacognition. I
      argue that any preparation that claims to tap into metacognition needs to be
      tested against leading nonmetacognition hypotheses such as Le Pelley's (2012)
      reinforcement-learning model. Progress in animal metacognition will come from the
      development of new assessment techniques that offer predictions contrary to
      nonmetacognition hypotheses. Animal metacognition will advance by applying
      skepticism about methods and interpretation while letting the animals (and their
      data) settle the debate.

PMID- 24866007
TI  - The uncertainty response in animal-metacognition researchers.
AB  - Kornell (2014, pp. 143-149) considers whether, and in what sense, animals may be
      considered metacognitive. He questions whether tests that rely on animals
      assessing their internal memory strength can provide useful data. He offers his
      own strategies for determining what internal cues animals use in making
      metacognitive judgments. We endorse his call for an increased focus on animals'
      metacognitive errors as true reflections of metacognitive states shorn of
      associative bases. We endorse a sharper focus on information-processing analyses
      of the executive or attentional level that metacognitive responses may occupy in
      animals' cognitive systems. Some of these analyses are being implemented in
      contemporary research, with positive results. Finally, we endorse the possibility
      that metacognition may not be an all-or-none thing, so that animals may share
      some facets--but not all facets--of metacognitive experience with humans.
      Kornell's interesting contribution makes clear that, in this area, the animal
      metacognition literature needs further theoretical sharpening.

PMID- 24866009
TI  - Great apes (Pan paniscus, Pan troglodytes, Gorilla gorilla, Pongo abelii) follow
      visual trails to locate hidden food.
AB  - Whether nonhuman primates understand causal relations beyond mere associations is
      still a matter of debate. We presented all four species of nonhuman great apes (N
      = 36) with a choice between 2 opaque, upside down cups after displacing them out
      of sight from their starting positions. Crucially, 1 of them had left a yogurt
      trail behind it. Great apes spontaneously used the trail to select the yogurt
      baited cup. Follow-up experiments demonstrated that chimpanzees distinguished
      trails based on the temporal order of cause and effect by ignoring trails that
      were already present before the reward was hidden. Additionally, chimpanzees did
      not select cups based on the amount of yogurt near them but instead preferred
      cups that signaled the endpoint of the trail. We conclude that apes' choices
      reveal sensitivity to a causal relation between cause (reward) and effect (trail)
      including their temporal order.

PMID- 24866011
TI  - Abstracts of the 2014 International MASCC/ISOO Symposium, June 26-28, 2014,
      Miami, Florida.

PMID- 24866013
TI  - Dynamic membrane structure induces temporal pattern formation.
AB  - The understanding of temporal pattern formation in biological systems is
      essential for insights into regulatory processes of cells. Concerning this
      problem, the present work introduces a model to explain the attachment/detachment
      cycle of MARCKS and PKC at the cell membrane, which is crucial for signal
      transduction processes. Our model is novel with regard to its driving mechanism:
      Structural changes within the membrane fuel an activator-inhibitor based global
      density oscillation of membrane related proteins. Based on simulated results of
      our model, phase diagrams were generated to illustrate the interplay of MARCKS
      and PKC. They predict the oscillatory behavior in the form of the number of
      peaks, the periodic time, and the damping constant depending on the amounts of
      MARCKS and PKC, respectively. The investigation of the phase space also revealed
      an unexpected intermediate state prior to the oscillations for high amounts of
      MARCKS in the system. The validation of the obtained results was carried out by
      stability analysis, which also accounts for further enhanced understanding of the
      studied system. It was shown, that the occurrence of the oscillating behavior is
      independent of the diffusion and the consumption of the reactants. The diffusion
      terms in the used reaction-diffusion equations only act as modulating terms and
      are not required for the oscillation. The hypothesis of our work suggests a new
      mechanism of temporal pattern formation in biological systems. This mechanism
      includes a classical activator-inhibitor system, but is based on the
      modifications of the membrane structure, rather than a reaction-diffusion system.

PMID- 24866014
TI  - Fluid domain patterns in free-standing membranes captured on a solid support.
AB  - We devise a methodology to fixate and image dynamic fluid domain patterns of
      giant unilamellar vesicles (GUVs) at sub-optical length scales. Individual GUVs
      are rapidly transferred to a solid support forming planar bilayer patches. These
      are taken to represent a fixated state of the free standing membrane, where
      lateral domain structures are kinetically trapped. High-resolution images of
      domain patterns in the liquid-ordered (lo) and liquid-disordered (ld) co
      existence region in the phase-diagram of ternary lipid mixtures are revealed by
      atomic force microscopy (AFM) scans of the patches. Macroscopic phase separation
      as known from fluorescence images is found, but with superimposed fluctuations in
      the form of nanoscale domains of the lo and ld phases. The size of the
      fluctuating domains increases as the composition approaches the critical point,
      but with the enhanced spatial resolution, such fluctuations are detected even
      deep in the coexistence region. Agreement between the area-fraction of domains in
      GUVs and the patches respectively, supports the assumption that the thermodynamic
      state of the membrane remains stable. The approach is not limited to specific
      lipid compositions, but could potentially help uncover lateral structures in
      highly complex membranes. 

PMID- 24866012
TI  - A membrane proximal helix in the cytosolic domain of the human APP interacting
      protein LR11/SorLA deforms liposomes.
AB  - Over the last decade, compelling evidence has linked the development of
      Alzheimer's disease (AD) to defective intracellular trafficking of the amyloid
      precursor protein (APP). Faulty APP trafficking results in an overproduction of
      Abeta peptides, which is generally agreed to be the primary cause of AD-related
      pathogenesis. LR11 (SorLA), a type I transmembrane sorting receptor, has emerged
      as a key regulator of APP trafficking and processing. It directly interacts with
      APP and diverts it away from amyloidogenic processing. The 54-residue cytosolic
      domain of LR11 is essential for its proper intracellular localization and
      trafficking which, in turn, determines the fate of APP. Here, we have found a
      surprising membrane-proximal amphipathic helix in the cytosolic domain of LR11.
      Moreover, a peptide corresponding to this region folds into an alpha-helical
      structure in the presence of liposomes and transforms liposomes to small vesicles
      and tubule-like particles. We postulate that this amphipathic helix may
      contribute to the dynamic remodeling of membrane structure and facilitate LR11
      intracellular transport.

PMID- 24866015
TI  - First report of Toxoplasma gondii seroprevalence in pet parrots in China.
AB  - Toxoplasmosis, caused by the obligate intracellular protozoan parasite Toxoplasma
      gondii, has become a serious public health problem worldwide. T. gondii can
      infect almost all warm-blooded animals, including parrots. However, little is
      known of T. gondii infection in parrots in China. Antibodies against T. gondii in
      311 parrots including 202 Budgerigars (Melopsittacus undulatus), 26 Lovebirds
      (Agapornis sp.), 22 Cockatiels (Nymphicus hollandicus), and 61 Alexandrine
      Parakeets (Psittacula eupatria) in the cities of Beijing and Weifang in north
      China were tested using the modified agglutination test (MAT). Twenty-six (8.36%)
      out of 311 serum samples were positive for T. gondii at the cutoff of 1:5. Among
      the four species, a higher seroprevalence of T. gondii was found in Cockatiels
      (13.64%, 95% confidence interval [CI] 0.00-27.98), although the difference was
      not statistically significant (p=0.61). Seropositivity rates against T. gondii in
      male parrots (10.43%, 95% CI 5.74-15.12) were not statistically different from
      that in female parrots (6.08%, 95% CI 2.23-9.93, p=0.17). The seropositivity of
      T. gondii in parrots from Weifang and Beijing was 11.11% (95% CI 6.13-16.09) and
      5.70% (95% CI 2.08-9.31), respectively. The seroprevalence varied in parrots of
      different age groups, ranging from 5.71% (95% CI 1.27-10.15) to 13.00% (95% CI
      6.41-19.69), however, the difference among age groups was not statistically
      significant (p=0.12). The seroprevalence of T. gondii infection in parrots in
      summer (11.63%, 95% CI 6.84-16.42) was significantly higher than in spring
      (4.32%, 95% CI 0.94-7.70, p=0.02). The results of the present survey indicated
      that parrots in China are exposed to T. gondii. To our knowledge, this is the
      first report of T. gondii seroprevalence in parrots in China.

PMID- 24866018
TI  - Location is everything: let-7b microRNA and TLR7 signaling results in a painful
      TRP.
AB  - Extracellular let-7b, a microRNA found in the central nervous system, affects
      neurons through its interaction with Toll-like receptor 7 (TLR7), but with
      divergent outcomes in different neurons. Lehmann et al. found that let-7b
      stimulation of cortical and hippocampal neurons led to neuronal apoptosis,
      whereas Park et al. report that let-7b activation of TLR7 stimulated the cation
      channel transient receptor potential A1 (TRPA1) on dorsal root ganglia sensory
      neurons and induced pain responses. The primary difference that may influence
      these distinct responses to let-7b is the localization of TLR7 to the endosome in
      the cortical and hippocampal neurons or the plasma membrane in the sensory
      neurons. These studies suggest that different types of neurons traffic TLR7 to
      distinct membrane locations, affecting the functional response of neurons to let
      7b stimulation. 

PMID- 24866016
TI  - C-reactive protein inhibits survivin expression via Akt/mTOR pathway
      downregulation by PTEN expression in cardiac myocytes.
AB  - C-reactive protein (CRP) is one of the most important biomarkers for
      arteriosclerosis and cardiovascular disease. Recent studies have shown that CRP
      affects cell cycle and inflammatory process in cardiac myocytes. Survivin is also
      involved in cardiac myocytes replication and apoptosis. Reduction of survivin
      expression is associated with less favorable cardiac remodeling in animal models.
      However, the effect of CRP on survivin expression and its cellular mechanism has
      not yet been studied. We demonstrated that treatment of CRP resulted in a
      significant decrease of survivin protein expression in a concentration-dependent
      manner in cardiac myocytes. The upstream signaling proteins of survivin, such as
      Akt, mTOR and p70S6K, were also downregulated by CRP treatment. In addition, CRP
      increased the protein and mRNA levels of PTEN. The siRNA transfection or specific
      inhibitor treatment for PTEN restored the CRP-induced downregulation of
      Akt/mTOR/p70S6K pathway and survivin protein expression. Moreover, pretreatment
      with a specific p53 inhibitor decreased the CRP-induced PTEN expression. ERK
      specific inhibitor also blocked the p53 phosphorylation and PTEN expression
      induced by CRP. Our study provides a novel insight into CRP-induced
      downregulation of survivin protein expression in cardiac myocytes through
      mechanisms that involved in downregulation of Akt/mTOR/p70S6K pathway by
      expression of PTEN. 

PMID- 24866019
TI  - A PLCgamma1-dependent, force-sensitive signaling network in the myogenic
      constriction of cerebral arteries.
AB  - Maintaining constant blood flow in the face of fluctuations in blood pressure is
      a critical autoregulatory feature of cerebral arteries. An increase in pressure
      within the artery lumen causes the vessel to constrict through depolarization and
      contraction of the encircling smooth muscle cells. This pressure-sensing
      mechanism involves activation of two types of transient receptor potential (TRP)
      channels: TRPC6 and TRPM4. We provide evidence that the activation of the gamma1
      isoform of phospholipase C (PLCgamma1) is critical for pressure sensing in
      cerebral arteries. Inositol 1,4,5-trisphosphate (IP3), generated by PLCgamma1 in
      response to pressure, sensitized IP3 receptors (IP3Rs) to Ca(2+) influx mediated
      by the mechanosensitive TRPC6 channel, synergistically increasing IP3R-mediated
      Ca(2+) release to activate TRPM4 currents, leading to smooth muscle
      depolarization and constriction of isolated cerebral arteries. Proximity ligation
      assays demonstrated colocalization of PLCgamma1 and TRPC6 with TRPM4, suggesting
      the presence of a force-sensitive, local signaling network comprising PLCgamma1,
      TRPC6, TRPM4, and IP3Rs. Src tyrosine kinase activity was necessary for stretch
      induced TRPM4 activation and myogenic constriction, consistent with the ability
      of Src to activate PLCgamma isoforms. We conclude that contraction of cerebral
      artery smooth muscle cells requires the integration of pressure-sensing signaling
      pathways and their convergence on IP3Rs, which mediate localized Ca(2+)-dependent
      depolarization through the activation of TRPM4. 

PMID- 24866021
TI  - Enteral naloxone for the treatment of opioid-induced constipation in the medical
      intensive care unit.
AB  - PURPOSE: To determine the safety and efficacy of enteral naloxone for the
      treatment of opioid-induced constipation in the medical intensive care unit
      (MICU). MATERIALS AND METHODS: This descriptive study included patients aged 18
      to 89 years admitted to the MICU between July 1, 2007, and June 30, 2012, who
      received scheduled opioids and at least 1 dose of enteral naloxone. All data were
      obtained from electronic charting systems. Efficacy was assessed by evaluating
      time to bowel movement (BM), number of naloxone doses until BM, and ability to
      tolerate tube feeds after receipt of enteral naloxone. Safety was assessed by
      comparing opioid requirements, heart rates, and systolic blood pressures before
      and during naloxone treatment. RESULTS: Fifteen of the 16 patients included in
      the final analysis passed BMs during the study period. The median time to BM was
      24.4 hours. The median number of naloxone doses received prior to passing a BM
      was 3. Seventy-eight percent of patients who were not receiving tube feeds at the
      time of naloxone administration received continuous tube feeds after naloxone
      initiation. No adverse effects associated with use of enteral naloxone were
      noted. CONCLUSIONS: Enteral naloxone appears safe for the treatment of opioid
      induced constipation in the MICU. Enteral naloxone may be effective in treating
      opioid-induced constipation; however, further studies are warranted.

PMID- 24866020
TI  - Multifaceted activities of type I interferon are revealed by a receptor
      antagonist.
AB  - Type I interferons (IFNs), including various IFN-alpha isoforms and IFN-beta, are
      a family of homologous, multifunctional cytokines. IFNs activate different
      cellular responses by binding to a common receptor that consists of two subunits,
      IFNAR1 and IFNAR2. In addition to stimulating antiviral responses, they also
      inhibit cell proliferation and modulate other immune responses. We characterized
      various IFNs, including a mutant IFN-alpha2 (IFN-1ant) that bound tightly to
      IFNAR2 but had markedly reduced binding to IFNAR1. Whereas IFN-1ant stimulated
      antiviral activity in a range of cell lines, it failed to elicit immunomodulatory
      and antiproliferative activities. The antiviral activities of the various IFNs
      tested depended on a set of IFN-sensitive genes (the "robust" genes) that were
      controlled by canonical IFN response elements and responded at low concentrations
      of IFNs. Conversely, these elements were not found in the promoters of genes
      required for the antiproliferative responses of IFNs (the "tunable" genes). The
      extent of expression of tunable genes was cell type-specific and correlated with
      the magnitude of the antiproliferative effects of the various IFNs. Although IFN
      1ant induced the expression of robust genes similarly in five different cell
      lines, its antiviral activity was virus- and cell type-specific. Our findings
      suggest that IFN-1ant may be a therapeutic candidate for the treatment of
      specific viral infections without inducing the immunomodulatory and
      antiproliferative functions of wild-type IFN. 

PMID- 24866022
TI  - The effect of Na-selenite treatment on the oxidative stress-antioxidants balance
      of multiple organ failure.
AB  - PURPOSE: Our study tested the hypothesis that sodium (Na)-selenite expression
      treatment can reduce oxidative stress and increase plasma antioxidants, whereas
      modulating white blood cell antigen expression in severe sepsis. Selenite is a
      well known cofactor of glutathione peroxidases and other antioxidant enzymes;
      therefore, one may expect an antioxidant effect of treatment. MATERIALS: We
      randomized 40 severe septic patients into treatment and control groups. Treatment
      group (n = 21) received 1000-MUg/2 hours Na-selenite load, followed by a 1000
      MUg/die medication. Oxidative stress markers, including malondialdehyde, maximal
      free radical production, and plasma antioxidants: free sulfhydryl groups,
      glutathione levels, and superoxide dismutase and catalase enzyme activity were
      measured. RESULTS: According to our results, the treatment regime successfully
      restored serum selenium levels. Treatment group developed a significant
      malondialdehyde increase by the fifth study day, whereas reactive oxygen species
      production decreased significantly. Reduced glutathione and plasma sulfhydryl
      groups showed no significant difference. Treatment group showed deteriorated
      expression of CD11a and slight increase of CD49d expression on monocytes
      throughout our study. CONCLUSIONS: Although our Na-selenite treatment regime
      successfully restored the selenium deficiency of severe septic patients,
      antioxidant and white blood cell antigen expression modulating effect of the
      therapy was not observed in our patient group.

PMID- 24866024
TI  - Hepatitis C in HIV-infected patients: impact of direct-acting antivirals.
AB  - Approximately 30% of HIV-infected patients are co-infected with hepatitis C virus
      (HCV). After the release of highly active antiretroviral therapy, liver disease
      has become the leading cause of morbidity and mortality in HIV patients. Prior to
      2011, HCV treatment with pegylated-interferon and ribavirin in HCV/HIV co
      infected patients only allowed 14-38% of patients with HCV genotype 1 to achieve
      a sustained virologic response (SVR). Additionally, treatment was commonly
      discontinued as a result of adverse events. Recently, simeprevir and sofosbuvir
      have been approved by the US Food and Drug Administration (FDA) for HCV mono
      infection. Sofosbuvir has been given FDA approval in co-infected patients
      offering unprecedented SVR rates and the potential for interferon-free therapy.
      HCV therapies that are in the pipeline offer improved treatment times, safety
      profiles, and rates of SVR. Despite these improvements, several new issues
      including adherence, drug-drug interactions with antiretroviral therapies,
      adverse events, resistance, and patient selection may complicate therapy. This
      article reviews the current status of direct-acting antivirals (DAA)-containing
      regimens for HIV/HCV co-infected patients in the USA. New results investigating
      telaprevir and boceprevir are also discussed as they are relevant for locations
      where new DAAs are not available. The impact future interferon-free therapies may
      have on co-infected patients is also discussed.

PMID- 24866025
TI  - Sowing the seeds of doubt: a narrative review on metacognitive training in
      schizophrenia.
AB  - The present article provides a narrative review of empirical studies on
      metacognitive training in psychosis (MCT). MCT represents an amalgam of cognitive
      behavioral therapy (CBT), cognitive remediation (CRT) and psychoeducation. The
      intervention is available in either a group (MCT) or an individualized (MCT+)
      format. By sowing the seeds of doubt in a playful and entertaining fashion, the
      program targets positive symptoms, particularly delusions. It aims to raise
      patients' awareness for common cognitive traps or biases (e.g., jumping to
      conclusions, overconfidence in errors, bias against disconfirmatory evidence)
      that are implicated in the formation and maintenance of psychosis. The majority
      of studies confirm that MCT meets its core aim, the reduction of delusions.
      Problems (e.g., potential allegiance effects) and knowledge gaps (i.e., outcome
      predictors) are highlighted. The preliminary data suggest that the individual MCT
      format is especially effective in addressing symptoms, cognitive biases and
      insight. We conclude that MCT appears to be a worthwhile complement to
      pharmacotherapy. 

PMID- 24866023
TI  - The evolution of insulin glargine and its continuing contribution to diabetes
      care.
AB  - The epoch-making discovery of insulin heralded a new dawn in the management of
      diabetes. However, the earliest, unmodified soluble insulin preparations were
      limited by their short duration of action, necessitating multiple daily
      injections. Initial attempts to protract the duration of action of insulin
      involved the use of various additives, including vasoconstrictor substances,
      which met with limited success. The subsequent elucidation of the chemical and
      three-dimensional structure of insulin and its chemical synthesis and
      biosynthesis allowed modification of the insulin molecule itself, resulting in
      insulin analogs that are designed to mimic normal endogenous insulin secretion
      during both fasting and prandial conditions. Insulin glargine was the first once
      daily, long-acting insulin analog to be introduced into clinical practice more
      than 10 years ago and is specifically designed to provide basal insulin
      requirements. It has a prolonged duration of action and no distinct insulin peak,
      making it suitable for once-daily administration and reducing the risk of
      nocturnal hypoglycemia that is seen with intermediate-acting insulins. Insulin
      glargine can be used in combination with prandial insulin preparations and non
      insulin anti-diabetic agents according to individual requirements. 

PMID- 24866027
TI  - Characterization of grain-specific peptide markers for the detection of gluten by
      mass spectrometry.
AB  - Global and targeted mass spectrometry-based proteomic approaches were developed
      to discover, evaluate, and apply gluten peptide markers to detect low parts per
      million (ppm) wheat contamination of oats. Prolamins were extracted from wheat,
      barley, rye, and oat flours and then reduced, alkylated, and digested with
      chymotrypsin. The resulting peptides were subjected to LC-MS/MS analysis and
      database matching. No peptide markers common to wheat, barley, and rye were
      identified that could be used for global gluten detection. However, many grain
      specific peptide markers were identified, and a set of these markers was selected
      for gluten detection and grain differentiation. Wheat flour was spiked into
      gluten-free oat flour at concentrations of 1-100,000 ppm and analyzed to
      determine the lowest concentration at which the wheat "contaminant" could be
      confidently detected in the mixture. The same 2D ion trap instrument that was
      used for the global proteomics approach was used for the targeted proteomics
      approach, providing a seamless transition from target discovery to application. A
      powerful, targeted MS/MS method enabled detection of two wheat peptide markers at
      the 10 ppm wheat flour-in-oat flour concentration. Because gluten comprises
      approximately 10% of wheat flour protein, the reported wheat gluten-specific
      peptides can enable detection of approximately 1 ppm of wheat gluten in oats. 

PMID- 24866029
TI  - A paper on the pace of recovery from diaphragmatic fatigue and its unexpected
      dividends.
AB  - Because the diaphragm is essential for survival, we wondered if it might be less
      vulnerable to the long-lasting effects of fatigue than limb muscles. Using a
      recently introduced magnetic probe to activate the phrenic nerves, we followed
      the evolution of twitch transdiaphragmatic pressure after inducing fatigue in
      healthy volunteers. Twenty-four hours after its induction, diaphragmatic fatigue
      had not fully recovered. Findings from this study later served as the foundation
      for incorporating a once-daily, T-tube-trial arm into a randomized controlled
      trial of techniques for ventilator weaning in intensive care unit patients and
      also influenced the design of a controlled trial of the weaning of tracheostomy
      patients who required prolonged ventilation. The research methodology was later
      employed to determine whether low-frequency fatigue is responsible for weaning
      failure. Employing a further modification of the technique--twitch airway
      pressure--it became evident that respiratory muscle weakness is a greater problem
      than fatigue in ventilated patients. Twitch airway pressure is now being used to
      document the prevalence and consequences of ventilator-induced respiratory muscle
      weakness. Our study--which began with a circumscribed, simple question--has
      yielded dividends in unforeseen directions, illustrating the fruitfulness of
      research into basic physiological mechanisms.

PMID- 24866030
TI  - What's new with survival prediction models in acute respiratory failure patients
      requiring extracorporeal membrane oxygenation.

PMID- 24866026
TI  - Type I interferons as regulators of human antigen presenting cell functions.
AB  - Type I interferons (IFNs) are pleiotropic cytokines, initially described for
      their antiviral activity. These cytokines exhibit a long record of clinical use
      in patients with some types of cancer, viral infections and chronic inflammatory
      diseases. It is now well established that IFN action mostly relies on their
      ability to modulate host innate and adaptive immune responses. Work in recent
      years has begun to elucidate the mechanisms by which type I IFNs modify the
      immune response, and this is now recognized to be due to effects on multiple cell
      types, including monocytes, dendritic cells (DCs), NK cells, T and B lymphocytes.
      An ensemble of results from both animal models and in vitro studies emphasized
      the key role of type I IFNs in the development and function of DCs, suggesting
      the existence of a natural alliance between these cytokines and DCs in linking
      innate to adaptive immunity. The identification of IFN signatures in DCs and
      their dysregulation under pathological conditions will therefore be pivotal to
      decipher the complexity of this DC-IFN interaction and to better exploit the
      therapeutic potential of these cells. 

PMID- 24866032
TI  - The complete mitochondrial genome of Melanargia asiatica (Lepidoptera:
      Nymphalidae: Satyrinae).
AB  - We sequenced the complete mitochondrial genome of Melanargia asiatica
      (Lepidoptera: Nymphalidae: Satyrinae). The entire closed circular molecule is
      15,142 bp long, containing 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes
      and a AT-rich region. All protein-coding genes (PCGs) initiate with the typical
      start codons ATN, with the exception of cox1, which uses CGA instead. Nine PCGs
      use the conventional stop codons (TAA) and the other four genes (cox1, cox2, nad4
      and nad5) use a single T as the stop codon. All tRNA genes display typical
      secondary cloverleaf structures, except for trnS1 (AGN), whose dihydrouridine
      (DHU) arm is replaced by a simple loop, as observed in all other lepidopterans.
      The AT-rich region is 319 bp in length and contains some features characteristic
      of lepidopterans, such as the ATAGA motif followed by a 19-bp poly-T stretch and
      a microsatellite-like repeat of (TA)6T(TA) preceded by the ATTTA motif.

PMID- 24866034
TI  - Focus on neurogenomics.

PMID- 24866033
TI  - The complete mitochondrial genome of the larvae Japanese grenadier anchovy Coilia
      nasus (Clupeiformes, Engraulidae) from Yangtze estuary.
AB  - The complete mitochondrial genome of the larvae Japanese grenadier anchovy Coilia
      nasus collected from Yangtze estuary was determined by next-generation
      sequencing. The mitogenome is a circular molecule 16,828 bp in length, including
      the typical structure of 13 protein-coding genes, 2 ribosomal RNA genes, 22
      transfer RNA genes and a control region. The TAS, central CSB and CSB were
      detected in the control region. The gene contents of the mitogenome are identical
      to those observed in most bony fishes. 

PMID- 24866035
TI  - Shedding light on learning.

PMID- 24866036
TI  - Impaired import: how huntingtin harms.

PMID- 24866037
TI  - Is there signal in the noise?

PMID- 24866038
TI  - The needle in the haystack.

PMID- 24866039
TI  - The (gamma) power to control our dreams.

PMID- 24866040
TI  - Pacemaker's burden.

PMID- 24866041
TI  - Genome-scale neurogenetics: methodology and meaning.
AB  - Genetic analysis is currently offering glimpses into molecular mechanisms
      underlying such neuropsychiatric disorders as schizophrenia, bipolar disorder and
      autism. After years of frustration, success in identifying disease-associated DNA
      sequence variation has followed from new genomic technologies, new genome data
      resources, and global collaborations that could achieve the scale necessary to
      find the genes underlying highly polygenic disorders. Here we describe early
      results from genome-scale studies of large numbers of subjects and the emerging
      significance of these results for neurobiology. 

PMID- 24866031
TI  - The functional diversity of essential genes required for mammalian cardiac
      development.
AB  - Genes required for an organism to develop to maturity (for which no other gene
      can compensate) are considered essential. The continuing functional annotation of
      the mouse genome has enabled the identification of many essential genes required
      for specific developmental processes including cardiac development. Patterns are
      now emerging regarding the functional nature of genes required at specific points
      throughout gestation. Essential genes required for development beyond cardiac
      progenitor cell migration and induction include a small and functionally
      homogenous group encoding transcription factors, ligands and receptors. Actions
      of core cardiogenic transcription factors from the Gata, Nkx, Mef, Hand, and Tbx
      families trigger a marked expansion in the functional diversity of essential
      genes from midgestation onwards. As the embryo grows in size and complexity,
      genes required to maintain a functional heartbeat and to provide muscular
      strength and regulate blood flow are well represented. These essential genes
      regulate further specialization and polarization of cell types along with
      proliferative, migratory, adhesive, contractile, and structural processes. The
      identification of patterns regarding the functional nature of essential genes
      across numerous developmental systems may aid prediction of further essential
      genes and those important to development and/or progression of disease.

PMID- 24866042
TI  - Prioritization of neurodevelopmental disease genes by discovery of new mutations.
AB  - Advances in genome sequencing technologies have begun to revolutionize
      neurogenetics, allowing the full spectrum of genetic variation to be better
      understood in relation to disease. Exome sequencing of hundreds to thousands of
      samples from patients with autism spectrum disorder, intellectual disability,
      epilepsy and schizophrenia provides strong evidence of the importance of de novo
      and gene-disruptive events. There are now several hundred new candidate genes and
      targeted resequencing technologies that allow screening of dozens of genes in
      tens of thousands of individuals with high specificity and sensitivity. The
      decision of which genes to pursue depends on many factors, including recurrence,
      previous evidence of overlap with pathogenic copy number variants, the position
      of the mutation in the protein, the mutational burden among healthy individuals
      and membership of the candidate gene in disease-implicated protein networks. We
      discuss these emerging criteria for gene prioritization and the potential impact
      on the field of neuroscience. 

PMID- 24866043
TI  - One gene, many neuropsychiatric disorders: lessons from Mendelian diseases.
AB  - Recent human genetic studies have consistently shown that mutations in the same
      gene or same genomic region can increase the risk of a broad range of complex
      neuropsychiatric disorders. Despite the steadily increasing number of examples of
      such nonspecific effects on risk, the underlying biological causes remain
      mysterious. Here we investigate the phenomenon of such nonspecific risk by
      identifying Mendelian disease genes that are associated with multiple diseases
      and explore what is known about the underlying mechanisms in these more 'simple'
      examples. Our analyses make clear that there are a variety of mechanisms at work,
      emphasizing how challenging it will be to elucidate the causes of nonspecific
      risk in complex disease. Ultimately, we conclude that functional approaches will
      be critical for explaining the causes of nonspecific risk factors discovered by
      human genetic studies of neuropsychiatric disorders. 

PMID- 24866046
TI  - Caregiver burden in mild cognitive impairment.
AB  - OBJECTIVES: We aimed to compare the rates of burden amongst caregivers of
      participants with mild cognitive impairment (MCI), compared to a control group.
      We also aimed to identify factors in both the caregiver and patient that are
      associated with significant levels of burden. METHOD: This was a cross-sectional
      study. Sixty-four participants with MCI, 36 control-participants and their
      respective caregivers/informants were recruited to a university research clinic.
      The proportion of those who showed clinically significant levels of burden was
      determined by a Zarit Burden Interview score of >21. The associations of burden
      in MCI-caregivers were calculated in the following categories; participant
      characteristics (including depressive symptoms, cognition and informant ratings
      of cognitive and behavioural change); caregiver characteristics; and the
      caregiving context. Multivariate analyses were performed to examine the relative
      contribution of individual variables to burden amongst MCI-caregivers. RESULTS:
      We found that 36% of MCI-caregivers reported clinically significant levels of
      burden, twice that of the control informant group. Participant behavioural
      problems contribute most to burden, with participant depression and possibly
      cognition also having a significant association. CONCLUSION: Caregiver burden is
      a considerable problem in MCI and shares some of the same characteristics as
      caregiver burden in dementia, namely a strong association with challenging
      behaviours in the patient. This has implications for further research and
      intervention studies.

PMID- 24866044
TI  - Large-scale genomics unveils the genetic architecture of psychiatric disorders.
AB  - Family study results are consistent with genetic effects making substantial
      contributions to risk of psychiatric disorders such as schizophrenia, yet robust
      identification of specific genetic variants that explain variation in population
      risk had been disappointing until the advent of technologies that assay the
      entire genome in large samples. We highlight recent progress that has led to a
      better understanding of the number of risk variants in the population and the
      interaction of allele frequency and effect size. The emerging genetic
      architecture implies a large number of contributing loci (that is, a high genome
      wide mutational target) and suggests that genetic risk of psychiatric disorders
      involves the combined effects of many common variants of small effect, as well as
      rare and de novo variants of large effect. The capture of a substantial
      proportion of genetic risk facilitates new study designs to investigate the
      combined effects of genes and the environment. 

PMID- 24866048
TI  - Determining target heart rate for exercising in a cardiac rehabilitation program:
      a retrospective study.
AB  - BACKGROUND: One of the well-established methods used to determine endurance
      training intensity for patients in outpatient cardiac rehabilitation (CR) is to
      take a percentage (70%-85%) of the maximal or peak heart rate (HRmax) from a
      recent postevent symptom-limited graded exercise test (GXT). Because many
      patients are referred to CR without having had a maximal GXT, a current practice
      is to use 30% to 50% above resting heart rate (RHR) to estimate endurance
      training intensity. OBJECTIVE: The purpose of this study was to determine if a
      target heart rate (THR) of 30% to 50% above RHR approximated a THR of 70% to 85%
      of the HRmax achieved on GXT (HRmax GXT) and provided equivalent exercise
      intensity based on ratings of perceived exertion (RPE) and metabolic equivalency
      thresholds (METs). METHODS: A retrospective chart review of 53 patients enrolled
      in CR and had documentation of postevent GXT was conducted to determine the
      patient's mean exercise heart rate (HR) achieved at each session to percentage
      above RHR and percentage HRmax GXT. Analysis was conducted to determine and
      compare patients' HRs, RPE, and MET levels when patients were exercising within
      the THR ranges of 30% to 50% above RHR and 70% to 85% HRmax GXT. RESULTS: A THR
      range of 30% to 50% above RHR approximated 60% to 70% HRmax GXT. Mean exercise
      HRs progressed from 39% to 49% above RHR sessions 2 to 6 with mean (SD) RPE of
      10.58 (0.55) to 11.44 (0.68) on the Borg scale and mean (SD) MET level of 2.91
      (0.55) to 3.31 (0.6). Mean exercise HRs progressed to 54% to 65% above RHR
      sessions 7 to 18 and approximated 70% to 73% HRmax GXT. Mean (SD) RPE at this
      intensity ranged from 11.57 (0.58) to 12.21 (0.53) with a mean (SD) MET level of
      3.47 (0.6) to 3.8 (0.77). CONCLUSION: In the observed population, a THR of 30% to
      50% above RHR underestimated the THR range of 70% to 85% HRmax GXT but provided
      adequate exercise intensity for patients at the beginning of a CR program based
      on percentage HRmax GXT, RPE and MET levels.

PMID- 24866049
TI  - Long-term outcome of obstetric anal sphincter injury repaired by experienced
      obstetricians.
AB  - OBJECTIVE: To examine the long-term outcomes of women with obstetric anal
      sphincter injury (OASI) repaired by obstetricians without the involvement of
      colorectal surgeons. METHODS: A retrospective cohort study was undertaken of
      women who had been admitted for delivery between 2004 and 2012. All OASIs had
      been repaired by experienced obstetricians using the end-to-end technique. An
      unexposed group (no OASI) was matched at a ratio of 1:1. Fecal incontinence was
      graded using a modified Wexner questionnaire. RESULTS: Overall, 113 OASIs were
      recorded. Sixty-seven (59.3%) and 71 (62.8%) women from the exposed and unexposed
      groups, respectively, agreed to participate in the study (P=0.9). Continence to
      both stool and gas was reported by 48 (71.6%) and 64 (90.1%) women in the exposed
      and unexposed groups, respectively (P=0.03). The incidence of urgency,
      dyspareunia, and use of a pad or constipating agents was the same in both groups.
      CONCLUSION: The long-term outcome of OASI repair performed by experienced
      obstetricians is comparable to that reported in the literature. Some women who
      did not sustain an OASI reported fecal incontinence, which suggests that only a
      proportion of fecal incontinence can be attributed to OASI.

PMID- 24866045
TI  - Whole-genome analyses of whole-brain data: working within an expanded search
      space.
AB  - Large-scale comparisons of patients and healthy controls have unearthed genetic
      risk factors associated with a range of neurological and psychiatric illnesses.
      Meanwhile, brain imaging studies are increasing in size and scope, revealing
      disease and genetic effects on brain structure and function, and implicating
      neural pathways and causal mechanisms. With the advent of global neuroimaging
      consortia, imaging studies are now well powered to discover genetic variants that
      reliably affect the brain. Genetic analyses of brain measures from tens of
      thousands of people are being extended to test genetic associations with signals
      at millions of locations in the brain, and connectome-wide, genome-wide scans can
      jointly screen brain circuits and genomes; these analyses and others present new
      statistical challenges. There is a growing need for the community to establish
      and enforce standards in this developing field to ensure robust findings. Here we
      discuss how neuroimagers and geneticists have formed alliances to discover how
      genetic factors affect the brain. The field is rapidly advancing with ultra-high
      resolution imaging and whole-genome sequencing. We recommend a rigorous approach
      to neuroimaging genomics that capitalizes on its recent successes and ensures the
      reliability of future discoveries. 

PMID- 24866051
TI  - The contribution of 18F-FDG PET/CT in a patient with cutaneous metastases of
      squamous cell carcinoma of the penis.
AB  - A 61-year-old patient was diagnosed with squamous cell carcinoma of the penis
      (SCCP) and treated with partial penectomy (pT1,N0,M0,G2). Seven months later, a
      palpable adenopathy was found in the left inguinal region. An (18)F-FDG PET/CT
      exploration showed hypermetabolic lymphadenopathies in inguinal, pelvic,
      retroperitoneal regions, in both lung hila and in the left supraclavicular
      regions. At the end of the 4th cycle of chemotherapy (cisplatin+5FU) the patient
      developed numerous skin metastases at the root of the left thigh and a pleural
      effusion in the right lung. In a new exploration with (18)F-FDG PET/CT the
      number, size and metabolic activity of known lymphadenopathies decreased. Right
      pleural carcinomatosis and intense FDG uptake in cutaneous metastases were
      observed. Weeks later, the patient died. (18)F-FDG-PET/TC may be useful in
      patients with SCCP and metastatic inguinal lymphadenopathies, to assess the
      response to chemotherapy and to detect other unsuspected metastases in the rare
      cases of cutaneous metastases. 

PMID- 24866052
TI  - Incidental FDG uptake in bilateral salpingitis due to Morgagni cyst hydatids on
      PET/CT scan in a patient with solitary pulmonary nodule.

PMID- 24866054
TI  - Characterization of the expression and inflammatory activity of NADPH oxidase
      after spinal cord injury.
AB  - Reactive oxygen species (ROS) and the NADPH oxidase (NOX) enzyme are both up
      regulated after spinal cord injury (SCI) and play significant roles in promoting
      post-injury inflammation. However, the cellular and temporal expression profile
      of NOX isotypes, including NOX2, 3, and 4, after SCI is currently unclear. The
      purpose of this study was to resolve this expression profile and examine the
      effect of inhibition of NOX on inflammation after SCI. Briefly, adult male rats
      were subjected to moderate contusion SCI. Double immunofluorescence for NOX
      isotypes and CNS cellular types was performed at 24 h, 7 days, and 28 days post
      injury. NOX isotypes were found to be expressed in neurons, astrocytes, and
      microglia, and this expression was dependent on injury status. NOX2 and 4 were
      found in all cell types assessed, while NOX3 was positively identified in neurons
      only. NOX2 was the most responsive to injury, increasing in both microglia and
      astrocytes. The biggest increases in expression were observed at 7 days post
      injury and increased expression was maintained through 28 days. NOX2 inhibition
      by systemic administration of gp91ds-tat at 15 min, 6 h or 7 days after injury
      reduced both pro-inflammatory cytokine expression and evidence of oxidative
      stress in the injured spinal cord. This study therefore illustrates the regional
      and temporal influence on NOX isotype expression and the importance of NOX
      activation in SCI. This information will be useful in future studies of
      understanding ROS production after injury and therapeutic potentials.

PMID- 24866056
TI  - Key aspects of a Flemish system to safeguard public health interests in case of
      chemical release incidents.
AB  - Although well-established protocols are available for emergency services and
      first-responders in case of chemical release incidents, a well-developed system
      to monitor and safeguard public health was, until recently, lacking in Flanders.
      We therefore developed a decision support system (DSS) to aid public health
      officials in identifying the appropriate actions in case of incidents. Although
      the DSS includes human biomonitoring as one of its key instruments, it also goes
      well beyond this instrument alone. Also other, complementary, approaches that
      focus more on effect assessment using in vitro toxicity testing, indirect
      exposures through the food chain, and parallel means of data collection (e.g.
      through ecosurveillance or public consultation), are integrated in the Flemish
      approach. Even though the DSS is set up to provide a flexible and structured
      decision tree, the value of expert opinion is deemed essential to account for the
      many uncertainties associated with the early phases of technological incidents.
      When the DSS and the associated instruments will be fully operational, it will
      provide a valuable addition to the already available protocols, and will
      specifically safeguard public health interests. 

PMID- 24866055
TI  - Sequestration of multiple RNA recognition motif-containing proteins by C9orf72
      repeat expansions.
AB  - GGGGCC repeat expansions of C9orf72 represent the most common genetic variant of
      amyotrophic lateral sclerosis and frontotemporal degeneration, but the mechanism
      of pathogenesis is unclear. Recent reports have suggested that the transcribed
      repeat might form toxic RNA foci that sequester various RNA processing proteins.
      Consensus as to the identity of the binding partners is missing and whole
      neuronal proteome investigation is needed. Using RNA fluorescence in situ
      hybridization we first identified nuclear and cytoplasmic RNA foci in peripheral
      and central nervous system biosamples from patients with amyotrophic lateral
      sclerosis with a repeat expansion of C9orf72 (C9orf72+), but not from those
      patients without a repeat expansion of C9orf72 (C9orf72-) or control subjects.
      Moreover, in the cases examined, the distribution of foci-positive neurons
      correlated with the clinical phenotype (t-test P < 0.05). As expected, RNA foci
      are ablated by RNase treatment. Interestingly, we identified foci in fibroblasts
      from an asymptomatic C9orf72+ carrier. We next performed pulldown assays, with
      GGGGCC5, in conjunction with mass spectrometry analysis, to identify candidate
      binding partners of the GGGGCC repeat expansion. Proteins containing RNA
      recognition motifs and involved in splicing, messenger RNA nuclear export and/or
      translation were significantly enriched. Immunohistochemistry in central nervous
      system tissue from C9orf72+ patients with amyotrophic lateral sclerosis
      demonstrated co-localization of RNA foci with SRSF2, hnRNP H1/F, ALYREF and hnRNP
      A1 in cerebellar granule cells and with SRSF2, hnRNP H1/F and ALYREF in motor
      neurons, the primary target of pathology in amyotrophic lateral sclerosis. Direct
      binding of proteins to GGGGCC repeat RNA was confirmed in vitro by ultraviolet
      crosslinking assays. Co-localization was only detected in a small proportion of
      RNA foci, suggesting dynamic sequestration rather than irreversible binding.
      Additional immunohistochemistry demonstrated that neurons with and without RNA
      foci were equally likely to show nuclear depletion of TDP-43 (chi(2) P = 0.75) or
      poly-GA dipeptide repeat protein inclusions (chi(2) P = 0.46). Our findings
      suggest two non-exclusive pathogenic mechanisms: (i) functional depletion of RNA
      processing proteins resulting in disruption of messenger RNA splicing; and (ii)
      licensing of expanded C9orf72 pre-messenger RNA for nuclear export by
      inappropriate association with messenger RNA export adaptor protein(s) leading to
      cytoplasmic repeat associated non-ATG translation and formation of potentially
      toxic dipeptide repeat protein. 

PMID- 24866059
TI  - Primates karyological diagnosis and management programs applications.
AB  - BACKGROUND: Captive primates are often maintained in groups without geographic
      origin or genetic heritage information. This could lead to an incorrect
      assignment of species, which could result in an inadequate management of the
      colonies. METHODS: We present a cytogenetic protocol adapted to be successfully
      used in an accurate taxonomic diagnosis of non-human primates (Platyrrhini),
      including lymphocyte culture, G- and C-banding, meiosis, and fluorescent in situ
      hybridization technique (FISH). RESULTS: Using classical cytogenetic diagnosis,
      the species status was determined in 541 Platyrrhini individuals. Of these, 99
      were previously erroneously sexed or assigned to a different species using only
      morphological characteristics. CONCLUSIONS: The cytogenetic results highlight the
      relevance of the genetic characterization of primates both in captivity and in
      the wild. These techniques had been used in our research group for more than 30
      years in different research projects, not only for characterizing hundreds of
      primates, but also different for topics regarding primates genomes and evolution.

PMID- 24866058
TI  - Contribution of food sources to the vitamin B12 status of South Indian children
      from a birth cohort recruited in the city of Mysore.
AB  - OBJECTIVE: There is evidence that subclinical vitamin B12 (B12) deficiency is
      common in India. Vegetarianism is prevalent and therefore meat consumption is
      low. Our objective was to explore the contribution of B12-source foods and
      maternal B12 status during pregnancy to plasma B12 concentrations. DESIGN:
      Maternal plasma B12 concentrations were measured during pregnancy. Children's
      dietary intakes and plasma B12 concentrations were measured at age 9.5 years; B12
      and total energy intakes were calculated using food composition databases. We
      used linear regression to examine associations between maternal B12 status and
      children's intakes of B12 and B12-source foods, and children's plasma B12
      concentrations. SETTING: South Indian city of Mysore and surrounding rural areas.
      SUBJECTS: Children from the Mysore Parthenon Birth Cohort (n 512, 47.1 % male).
      RESULTS: Three per cent of children were B12 deficient (<150 pmol/l). A further
      14 % had 'marginal' B12 concentrations (150-221 pmol/l). Children's total daily
      B12 intake and consumption frequencies of meat and fish, and micronutrient
      enriched beverages were positively associated with plasma B12 concentrations
      (P=0.006, P=0.01 and P=0.04, respectively, adjusted for socio-economic indicators
      and maternal B12 status). Maternal pregnancy plasma B12 was associated with
      children's plasma B12 concentrations, independent of current B12 intakes
      (P<0.001). Milk and curd (yoghurt) intakes were unrelated to B12 status.
      CONCLUSIONS: Meat and fish are important B12 sources in this population.
      Micronutrient-enriched beverages appear to be important sources in our cohort,
      but their high sugar content necessitates care in their recommendation. Improving
      maternal B12 status in pregnancy may improve Indian children's status.

PMID- 24866057
TI  - Hydrogen peroxide responsive miR153 targets Nrf2/ARE cytoprotection in paraquat
      induced dopaminergic neurotoxicity.
AB  - Epidemiological and animal studies suggest that environmental toxins including
      paraquat (PQ) increase the risk of developing Parkinson's disease (PD) by
      damaging nigrostriatal dopaminergic neurons. We previously showed that
      overexpression of a group of microRNAs (miRs) affects the antioxidant promoting
      factor, Nrf2 and related glutathione-redox homeostasis in SH-SY5Y dopaminergic
      neurons. Although, dysregulation of redox balance by PQ is well documented, the
      role for miRs and their impact have not been elucidated. In the current study we
      investigated whether PQ impairs Nrf2 and its related cytoprotective machinery by
      misexpression of specific fine tune miRs in SH-SY5Y neurons. Real time PCR
      analysis revealed that PQ significantly (p<0.05) increased the expression of
      brain enriched miR153 with an associated decrease in Nrf2 and its function as
      revealed by decrease in 4* ARE activity and expression of GCLC and NQO1. Also, PQ
      and H2O2-induced decrease in Nrf2 3' UTR activity was restored on miR153 site
      mutation suggesting a 3' UTR interacting role. Overexpression of either anti
      miR153 or Nrf2 cDNA devoid of 3' UTR prevented PQ and H2O2-induced loss in Nrf2
      activity confirming that PQ could cause miR153 to bind to and target Nrf2 3' UTR
      thereby weakening the cellular antioxidant defense. Adenovirus mediated
      overexpression of cytoplasmic catalase (Ad cCAT) confirmed that PQ induced miR153
      is hydrogen peroxide (H2O2) dependent. In addition, Ad cCAT significantly
      (p<0.05) negated the PQ induced dysregulation of Nrf2 and function along with
      minimizing ROS, caspase 3/7 activation and neuronal death. Altogether, these
      results suggest a critical role for oxidant mediated miR153-Nrf2/ARE pathway
      interaction in paraquat neurotoxicity. This novel finding facilitates the
      understanding of molecular mechanisms and to develop appropriate management
      alternatives to counteract PQ-induced neuronal pathogenesis. 

PMID- 24866060
TI  - A projected landmark method for reduction of registration error in image-guided
      surgery systems.
AB  - PURPOSE: Image-guided surgery systems are limited by registration error, so
      practical and effective methods to improve accuracy are necessary. A projection
      point-based method for reducing the surface registration error in image-guided
      surgery was developed and tested. METHODS: Checkerboard patterns are projected on
      visible surfaces to create projected landmarks over a region of interest. Surface
      information thus becomes available in the form of point clouds of surface point
      coordinates with submillimeter resolution. The reconstructed 3D point cloud is
      registered using iterative closest point (ICP) approximation to a 3D point cloud
      extracted from preoperative CT images of the same region of interest. The
      projected landmark surface registration method was compared with two other
      methods using a facial surface phantom: (a) landmark registration using
      anatomical features, and (b) surface matching based on an additional 40 surface
      points. RESULTS: The mean error for the projected landmark surface registration
      method was 0.64 mm, which was 47.4 and 35.3 % lower relative to mean errors of
      the anatomical landmark registration and the surface-matching methods,
      respectively. After applying the proposed method, using target registration error
      as a gold standard, the resulting mean error was 1.1 mm or a reduction of 61.2 %
      compared to the anatomical landmark registration. CONCLUSION: Optical
      checkerboard pattern projection onto visible surfaces was used to acquire surface
      point clouds for image-guided surgery registration. A projected landmark method
      eliminated the effects of unwanted and overlapping points by acquiring the
      desired points at specific locations. The results were more accurate than
      conventional landmark or surface registration.

PMID- 24866062
TI  - Cerebral edema in children with diabetic ketoacidosis: vasogenic rather than
      cellular?
AB  - Cerebral edema (CE) is accumulation of water in the intracellular or
      extracellular spaces of the brain. Vasogenic edema occurs when there is breakdown
      of the tight endothelial junctions of the blood-brain barrier (BBB), leading to
      extravasation of intravascular protein and fluid into the interstitial space of
      the brain. In cellular edema the BBB remains intact and there is swelling of
      astrocytes with corresponding reduction in extracellular space. In this review we
      bring together clinical evidence from neuropathology and cerebral magnetic
      resonance (MR) studies in pediatric patients presenting in diabetic ketoacidosis
      (DKA), and use applied physiology to understand whether CE complicating DKA is
      vasogenic, rather than cellular in origin. Because the first-line of defense
      against CE is the interface between the intravascular compartment and the
      extracellular space in the brain much of the focus in this review is the BBB. The
      principal pathologic finding in fatal cases is perivascular with BBB disruption
      and albumin extravasation, suggesting increased vascular permeability. DKA
      induces an inflammatory response and the mechanism of BBB transcellular
      permeability may be an immunologic cascade that disrupts tight junctions. The
      principal MR finding in subclinical cases of CE is vasogenic rather than cellular
      edema. We propose that the following physiology be considered when treating
      cases: bolus dose of intravenous mannitol may result in fall in serum sodium
      concentration, and therefore clinical worsening. Failure to respond to mannitol
      should prompt the use of 3% hypertonic saline (HS). Bolus dose of intravenous 3%
      HS is expected to effect vasogenic edema provided that the reflection coefficient
      is close to 1. Failure to respond to 3% HS should prompt the use of mannitol. 

PMID- 24866061
TI  - Anti-hyperuricemic and nephroprotective effects of Rhizoma Dioscoreae septemlobae
      extracts and its main component dioscin via regulation of mOAT1, mURAT1 and mOCT2
      in hypertensive mice.
AB  - Rhizoma Dioscoreae septemlobae (RDSE) has been widely used for the treatment of
      hyperuricemia in China. However, the therapeutic mechanism has been unknown. This
      study investigated the antihyperuricemic mechanisms of the extracts obtained from
      RDSE and its main component dioscin (DIS) in hyperuricemic mice. Hyperuricemic
      mice were induced by potassium oxonate (250 mg/kg). RDSE or DIS was orally
      administered to hyperuricemic mice at dosages of 319.22, 638.43, 1276.86
      mg/kg/day for 10 days, respectively. Uric acid or creatinine in serum and urine
      was determined by HPLC or HPLC-MS/MS, respectively. The xanthine oxidase (XO)
      activities in mice liver were examined in vitro. Protein levels of organic anion
      transporter 1 (mOAT1), urate transporter 1 (mURAT1) and organic cation
      transporter 2 (mOCT2) in the kidney were analyzed by western blotting. The
      results indicated that uric acid and creatinine in serum were significantly
      increased by potassium oxonate, as compared to that of control mice. Compared
      saline-treated group, after RDSE treatment in the high and middle dose, the
      expression of mOAT1 increased 47.98 and 54.48 %, respectively, which accompanied
      with the decreased expression of mURAT1 (47.63 %) in high dose. After DIS
      treatment in high, middle and low dose, the expression of mOAT1 increased 23.93,
      32.80 and 25.28 % compared to saline-treated group, respectively, which
      accompanied with the decreased expression of mURAT1 (51.07, 51.42 and 51.35 %).
      However, RDSE and DIS displayed a weak XO inhibition activity compared with
      allopurinol. Therefore, RDSE and DIS processed uricosuric and nephroprotective
      actions by regulation of mOAT1, mURAT1 and mOCT2. 

PMID- 24866063
TI  - How can cerebral edema during treatment of diabetic ketoacidosis be avoided?
AB  - Cerebral edema during diabetic ketoacidosis (DKA) is a rare complication but it
      can be devastating, with significant mortality and long-term morbidity. Certain
      risk factors have been teased out with some large case-control studies, but more
      research needs to be done to make management guidelines safer. This article will
      discuss how DKA might be prevented from occurring in the first instance, known
      risk factors for cerebral edema, fluid and insulin management, the importance of
      careful monitoring during DKA treatment, and the importance of recognizing and
      acting on the earliest symptoms to prevent long-term harm. 

PMID- 24866064
TI  - The International Society of Pediatric and Adolescent Diabetes guidelines for
      management of diabetic ketoacidosis: Do the guidelines need to be modified?
AB  - The current version of the International Society of Pediatric and Adolescent
      Diabetes (ISPAD) guidelines for management of diabetic ketoacidosis (DKA) is
      largely based on the Lawson Wilkins Pediatric Endocrine Society/European Society
      of Pediatric Endocrinology (LWPES/ESPE) consensus statement on DKA in children
      and adolescents published in 2004. This article critically reviews and presents
      the most pertinent new data published in the past decade, which have implications
      for diagnosis and management. Four elements of the guidelines warrant
      modification: (i) The definition of DKA; (ii) insulin therapy; (iii) water and
      salt replacement; and (iv) blood beta-hydroxybutyrate measurements for the
      management of DKA. 

PMID- 24866065
TI  - Detection of RAS mutation by pyrosequencing in thyroid cytology samples.
AB  - INTRODUCTION: Fine-needle aspiration cytology (FNAC) is the primary means to
      distinguish benign from malignant thyroid nodules. However, adjunctive diagnostic
      tests are needed as 20-40% of FNAC are inconclusive. RAS mutations have been
      described in differentiated thyroid cancer and they could be used as tumor
      markers. However, their prevalence varies widely among studies, probably as a
      result of the detection methods used. We investigated whether the pyrosequencing
      method can be applied to detect NRAS and KRAS mutations in thyroid aspirates.
      PATIENTS AND METHODS: A total of 37 thyroid aspirates, including benign
      hyperplastic nodules (HBN, N = 16) and follicular thyroid carcinomas (FTC, N =
      21) were analyzed for the presence of NRAS(61) and KRAS(13) mutations. RESULTS: A
      RAS mutation was found in 31% and 62% of BN and FTC respectively. Most samples
      displayed a percentage of mutated alleles lower than 50% (median = 30.8% and
      15.3% in FTC and HBN respectively), a result compatible with the presence of
      extra-nodular cells contaminating the FNA or with the subclonal nature of both
      types of thyroid nodules. DISCUSSION: Pyrosequencing is a reliable assay to
      detect RAS mutations in fine-needle thyroid aspirates. CONCLUSIONS: The low
      specificity and sensitivity limit the power of this test to distinguish between
      FTC and benign nodules in inconclusive FNACs.

PMID- 24866066
TI  - Long-term function of parathyroid subcutaneous autoimplantation after presumed
      total parathyroidectomy in the treatment of secondary hyperparathyroidism. A
      clinical retrospective study.
AB  - INTRODUCTION: Parathyroidectomy (PTx) is recommended in patients affected by
      secondary hyperparathyroidism (2HPT) of chronic kidney disease-mineral bone
      disorders (CKD-MBD), resistant to medical treatment. Analyzing total
      parathyroidectomy with muscular or subcutaneous autoimplantation (TPai) outcomes
      in hemodialysis (HD) 2HPT patients, and monitoring intact parathyroid hormone
      (iPTH) levels, we evaluated long-term functional results of subcutaneous
      parathyroid glandular tissue autoimplantation. METHODS: 40 HD 2HPT patients,
      resistant to medical treatment, and awaiting for renal transplantation, underwent
      total parathyroidectomy with subcutaneous autoimplantation of 9-12 fragments of
      not nodular hyperplasia parathyroid tissue in not dominant forearm. iPTH were
      analyzed 24 h, and 3-6-12-24 months after surgery. The 1.08-6.99 pmol/L range was
      taken as reference of normal iPTH level based on which eu- (1.08-6.99), hypo-
      (<1.08), aparathyroidism (0) and persistence or relapse (>6.99) of disease were
      determined. RESULTS: In every case PTai determined an extraordinary improvement
      of quality of life, associated with a notable reduction of iPTH serum level.
      Immediate normalization of iPTH was achieved in 50% of cases; hypoparathyroidism
      in 25% of cases and persistence of disease in 25% were observed. Long term follow
      up showed a reduction of hypoparathyroidism and an increase of relapse rate up to
      20%. Grafting resection was never performed. DISCUSSION: Subcutaneous
      autotrasplantation is a very simple and fast surgical technique. Nevertheless,
      similar success and recurrence rates were reported following muscular or
      subcutaneous grafting, as confirmed in our experience. CONCLUSIONS: Subcutaneous
      grafting was effective as muscular implantation, with comparable functional
      results, but avoiding its potential complications.

PMID- 24866067
TI  - Surgical site infection: an observer-blind, randomized trial comparing
      electrocautery and conventional scalpel.
AB  - AIM: To evaluate the incidence of surgical site infection (SSI) based on the type
      of scalpel used for incisions in the skin and in subcutaneous tissues. METHODS:
      Observer-blind, randomized equivalence clinical trial with two arms
      (electrocautery versus conventional scalpel) which evaluated 133 women undergoing
      elective abdominal gynecologic oncology surgery. A simple randomization
      stratified by body mass index (BMI: 30 kg/m(2)) was carried out. Women were
      evaluated at 14 and 30 days following the operation. A multivariate analysis was
      performed in order to check whether the type of scalpel would be a risk factor
      for SSI. RESULTS: Group arms were balanced for all variables, excepted for
      surgical time, which was significantly higher in the electrocautery group (mean:
      161.1 versus 203.5 min, P = 0.029). The rates of SSI were 7.4% and 9.7%,
      respectively, for the conventional scalpel and electrocautery groups (P = 0.756).
      The exploratory multivariate model identified body mass index >=30 kg/m(2) (OR =
      24.2, 95% CI: 2.8-212.1) and transverse surgical incision (OR = 8.1, 95% CI: 1.5
      42.6) as independent risk factors for SSI. The type of scalpel used in surgery,
      when adjusted for these variables and the surgery time, was not a risk factor for
      SSI. CONCLUSION: This study showed that the SSI rates for conventional scalpel
      and electrocautery were not significantly different. These results were
      consistent with others reported in the literature and would not allow a surgeon
      to justify scalpel choice based on SSI. TRIAL NUMBER: NCT01410175 (Clinical
      Trials - NIH).

PMID- 24866068
TI  - The role of a multidisciplinary approach in the choice of the best surgery
      approach in a super-super-obesity case.
AB  - INTRODUCTION: Obesity is a multifactorial chronic disease caused by a combination
      of hereditary, metabolic, dietary, cultural, social and psychological factors.
      Conservative treatments, such as diet and physical exercises, revealed a lack of
      long-term efficacy in patients with an extremely high BMI (>60 kg/m(2)). METHODS:
      We present a multidisciplinary approach in a patient with an extremely high BMI:
      a twenty-one years old woman with a BMI 102 kg/m(2) (body weight 313 kg * height
      175 cm) disabled to walk with severe depression and a psychological pattern of
      sweet eater and binge eating disorder. She was also amenorrheic and suffered from
      metabolic syndrome. The psychological assessment and the social-familial support
      were defined as priorities. Afterward, physical rehabilitation, behavior therapy,
      hypocaloric diet followed by intragastric balloon were planned as preoperative
      treatment. Finally a surgical program was scheduled: Sleeve Gastrectomy as first
      step of Biliopancreatic Diversion with Duodenal Switch. RESULTS: Sixteenth months
      after the Sleeve Gastrectomy the weight was 130 kg (Excess Weight Loss = 74%)
      with a resumption of the menstrual cycle and a normalization of the metabolic
      syndrome. CONCLUSION: Due to the results obtained with both surgery and an
      excellent psychological supporting network we decided not to perform the expected
      Biliopancreatic Diversion with Duodenal Switch. The timing of bariatric surgery
      in superobesity patients is a milestone, but the cooperation among the
      specialists is essential for the choice of the best successful surgery. The
      multidisciplinary team should point to a comprehensive tailored management,
      considering motivation, compliance and adherence to a long-term follow-up as the
      keys for surgical success.

PMID- 24866069
TI  - Quality of life in cancer survivors 5 years or more after total gastrectomy: a
      case-control study.
AB  - INTRODUCTION: This study investigated how total gastrectomy (TG), along with
      memories of cancer, affect the subjective wellness of survivors long after
      surgery. Rational approaches for effectively improving the quality of life (QoL)
      of these survivors were suggested. METHODS: Between 2008 and 2013, QoL data of
      gastric cancer patients who underwent a curative TG, were obtained at 5-year
      postoperative follow-up visits (5-year survivors) and at visits beyond 5 years
      (long-term survivors). The control groups for these survivor groups were
      constructed from volunteers who visited our health-examination center for annual
      medical checkups. The Korean versions of the European Organization for Research
      and Treatment (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) and the
      gastric cancer specific module, the EORTC QLQ-STO22, were used to assess QoL.
      RESULTS: Five-year survivors showed worse QoL compared to the control group in
      role functioning, social functioning, nausea/vomiting, appetite loss, financial
      difficulties, reflux, eating restrictions, taste, and body image, and better QoL
      in the emotional and cognitive functioning scales. In long-term survivors,
      deterioration in QoL were still apparent in financial difficulties, reflux, and
      eating restrictions, while QoL differences in the remaining scales had
      diminished. DISCUSSION: Surviving 5 years after TG does not result in living in a
      carefree state in terms of QoL. After 5 postoperative years, survivors still need
      extended care for deteriorated QoL indicators due to symptomatic, behavioral, and
      financial consequences of surgery. CONCLUSION: While relevant clinical and
      institutional approaches are required for corresponding declines in QoL, such
      efforts must extend beyond 5 postoperative years.

PMID- 24866071
TI  - Anomalous lung cancer cell carriage: a historical review with present prospects.
AB  - It is a scientific axiom that anomalous findings may imply imperfections in
      current concepts and are often a stimulus to discovery. Therefore, this article
      surveys the publications extending from 1818 to 1897 in order to quantify the
      experiences of the medical masters because they were perturbed that, at autopsy,
      lung cancer cells usually failed to cross the midline to the opposite lung.
      Accordingly, there is need to recognize that this is actually an anomalous
      phenomenon which requires explanation. In all probability, the anomaly is
      explicable on the basis of the workings of a hitherto hidden Factor which
      originates in lung parenchyma. Therefore, it is argued that the Factor would
      perform best in the contralateral lung. Finally, it is hypothesized that its
      conspicuous effect in the contralateral lung is what explains the anomaly of low
      or no colonization of that most eligible site in the body. Incidentally, surgical
      cannulation and videomicroscopic retrieval of dying and living cancer cells will
      provide subsets for research on the phenomenon proper. 

PMID- 24866070
TI  - Efficacy of combined treatment for anaplastic thyroid carcinoma: results of a
      multinstitutional retrospective analysis.
AB  - INTRODUCTION: Anaplastic thyroid carcinoma (ATC) is a killer tumor, characterized
      by local invasiveness, risk of recurrence and very poor prognosis. Due to its
      rarity, clinical case studies concerning management are lacking. METHODS: We
      retrospectively reviewed a multinstitutional clinical series of 114 consecutive
      patients treated between 1996 and 2012 for ATC. The outcomes of a combined
      treatment were analyzed considering the impact of surgery and radiotherapy on
      survival. RESULTS: Patients were divided in groups A and B considering tumor size
      (tumor lesser and larger than 5 cm). Surgery was carried out in 71 patients,
      radiotherapy in 89 patients. Tracheostomy and endoprothesis were used
      respectively in 48.7% and in 25.6% of patients. The mean survival was 5.35 (+/
      3.2) months with no significant difference in group A vs group B. A better
      survival was observed in both groups of patients undergone a surgical treatment
      compared to no treated patients (p = 0.001 and p = 0.0001) or to patients
      undergone radiotherapy alone (p = 0.047 and p = 0.0001). Combination of surgery
      and radiotherapy significantly improved outcome (p = 0.017). DISCUSSION: Despite
      disappointing results from single therapeutic approach, multimodal strategy has
      progressively become the treatment of choice in ATC, with surgery being the
      cornerstone of the management. CONCLUSION: Although dismal prognosis, the
      combined treatment might significantly improves locoregional disease control,
      achieving acceptable survival in selected patients and adequate palliation of the
      symptoms.

PMID- 24866072
TI  - Incidental carcinoma of the thyroid.
AB  - The diagnosis of incidental thyroid carcinoma in patients submitted to
      thyroidectomy for a benign disease is quite frequent. A retrospective analysis
      was performed on 455 patients submitted to surgical intervention in order to
      establish the incidence of this kind of carcinoma. Two hundred fifty-six patients
      (56%) were affected by benign disease (176 multinodular goiter, 12 uninodular
      goiter, 1 Plummer disease and 67 Basedow disease) and 202 (44%) by carcinoma. In
      28 of 256 patients (11%), affected by benign disease, occurred a histological
      diagnosis of thyroid carcinoma, (10 papillary carcinoma, 1 follicular carcinoma,
      29 papillary carcinoma follicular variant). In this study it's considered
      incidental thyroid carcinoma the one occurred in patients who never underwent
      Fine Needle Aspiration (FNA) and there were no suspicious features in all exams
      that may suggest the presence of carcinoma. Twenty-three of the 40 incidental
      carcinoma (57.5%) were microcarcinomas. Ten patients had a sincronous carcinoma.
      Actually, these patients are still in a follow up program and no recurrency of
      disease is occasionally observed. This study shows that the only way to put
      doubts on the real benignity of the disease is the fine needle aspiration; there
      are no other instruments that could identify the occurrence of the carcinoma.
      Moreover in the majority of cases the incidental carcinoma is a microcarcinoma,
      it doesn't reach significant volume, may be not centered by a FNA, but in most
      cases it's not really biologically aggressive. 

PMID- 24866073
TI  - Pregnancy after laparoscopic gastric banding: maternal and neonatal outcomes.
AB  - INTRODUCTION: Laparoscopic Adjustable Gastric Banding (LAGB) is a safe and
      effective treatment for obesity. A strong evidence links weight loss with
      improved fertility outcomes and reduced gestational complications in subsequent
      pregnancies. Our aim is to describe the impact of LAGB on maternal and neonatal
      outcomes. METHODS: Data were collected retrospectively from the database of our
      University Center for the Multicentric Treatment of Severe Obesity. From January
      2006 to December 2011, 438 patients underwent LAGB. Of these, 140 women of
      reproductive age (18-46 years old) were included in our study. The following
      parameters were registered during follow-up: number of pregnancies, delivery and
      miscarriage, time from LAGB to pregnancy, band adjustments, weight gain during
      pregnancy, gestational and obstetrical complications (gestational diabetes
      mellitus, hypertensive disorders, prolonged labor), mode of delivery, neonatal
      birth weight and complications (low birth weight, IUGR, prematurity, macrosomy).
      RESULTS: We registered 26 pregnancies with a total of 22 babies born and 4
      miscarriages. The mean time from LAGB to pregnancy was 15.8 months. Band
      adjustments were performed in 100% of patients during the first trimester; the
      average weight gain at the end of pregnancy was 14.66 kg. None presented
      gestational or obstetrical complications. One patient presented band slippage,
      which required surgery, and one patient presented iron-deficiency anemia. 100% of
      deliveries were by cesarean section. No perinatal complications or malformations
      were recorded, and the average baby weight was 3027 g. CONCLUSION: LAGB is a safe
      procedure, well tolerated during pregnancy and without negative implications on
      both the mother and the baby. According to our experience and recent studies,
      band loosening should be reserved to symptomatic patients to avoid unhealthy
      weight gain.

PMID- 24866074
TI  - ACTH-secreting neuroendocrine pancreatic tumor: a case report.
AB  - INTRODUCTION: Incidence of neuroendocrine tumor (NET) is increased in the last
      thirty years from 1.1 to 5.2 cases per 100,000 people in the United States. They
      can originate from the pancreatic gland and for the majority of cases are not
      functioning (80%). A small percentage of functioning may produce
      adrenocorticotropic hormone (ACTH) and lead to ectopic ACTH Syndrome (EAS),
      responsible of Cushing-Syndrome. RESULTS: We present a case of a 30 year-old
      woman suffering from EAS due to a neoformation of the pancreatic tail of the
      maximum diameter of 4 cm. The lesion was resectable at preoperatory imaging. The
      patient was subjected to distal splenopancreasectomy. Histological examination
      showed a well-differentiated neuroendocrine carcinoma pT3N0. The postoperative
      course was regular. At two years of follow-up patient is almost completely
      asymptomatic for Cushing's but she has developed multiple liver metastases, for
      which she began chemotherapy. DISCUSSION: p-NET responsible for EAS is usually
      malignant and the radical treatment of excision of the lesion is not possible
      because they occur at the time of diagnosis with liver metastases or
      unresectable. Our patient had a mass at the time of diagnosis resectable but
      despite radical surgery, she has developed multiple liver metastases at two years
      and she was undergoing chemotherapy. CONCLUSIONS: In agreement with previous
      literature we confirm the aggressive nature of pancreatic tumors secreting ACTH,
      despite radical surgery. Conversely, surgical treatment is effective on the
      resolution of clinical symptoms.

PMID- 24866076
TI  - Localization of sentinel lymph node in breast cancer. A prospective study.
AB  - INTRODUCTION: Sentinel Lymph Node Biopsy (SLNB) is the standard of care for
      staging axillary lymph nodes in women with breast cancer and clinically negative
      nodes. It is associated with reduced arm morbidity, moderated or severe
      lymphoedema, and a better quality of life in comparison with standard axillary
      treatment. Unfortunately, skip metastases makes all minimally invasive
      approaches, such as axillary sampling, unreliable. The aim of the present
      clinical prospective study is to evaluate the position of SLN in an important
      number of cases and establish the real incidence of skip metastases in clinically
      node-negative patients. PATIENTS AND METHODS: A cohort of 898 female patients
      with breast carcinoma was considered, from 2001 to 2008. Once SLN was localized,
      by means of radio-colloid or blue dye staining, and isolated, a biopsy was
      performed. Only those positive for metastases were submitted to axillary
      dissection. RESULTS: Only in nine cases a SLN was not isolated. We had 819 cases
      of first level SLN (group A) and 69 cases of second level SLN (group B).
      Considering all of 889 cases, SLN was localized in the second level in 69
      patients (7.8%); but if we consider metastatic SLN alone (340 cases), it was in
      the second level in 23 subjects (6.8%). In total, we had a positive second level
      SLN in 2.3% of cases (23/889). CONCLUSION: Second level SLN could be considered
      only an anomalous lymphatic axillary drainage and it does not linked to
      particular histological variants of the primitive tumour. In our study, skip
      metastases were recognized in only 2.6% of cases, therefore, whenever a SLN is
      not isolated for any reason, the first level sampling represent a viable
      operative choice.

PMID- 24866075
TI  - Adrenocortical carcinoma: what the surgeon needs to know. Case report and
      literature review.
AB  - Adrenocortical carcinoma is a rare and aggressive cancer and its prognosis is
      frequently unsatisfactory. Due to its rarity there's a lack of prospective
      randomized studies. Without experience in the approach of this kind of tumor,
      managing becomes challenging and, moreover, we have only few recommendations,
      based on weak evidence. We report a case that has some peculiarities and is an
      excellent food for thought. Then we deal with a literature review to highlight
      and summarize most significant aspects of epidemiology, clinic, diagnosis,
      therapy and prognosis in an exquisitely surgical point of view. 

PMID- 24866077
TI  - Relatives of Crohn's disease patients and breast cancer: an overlooked condition.
AB  - Recent data suggest that patients suffering from Crohn's disease (CD) may be at
      higher risk of developing extra-intestinal malignancies. This is attributed to
      inflammation and immunodepression due to medications. However, a genetic
      predisposition cannot ruled out. In the present study we investigated the
      prevalence of breast cancer in first-degree female relatives of CD patients
      compared with relatives of patients without evidence of gastrointestinal
      diseases. A total of 1302 female first-degree relatives of CD patients and 1294
      relatives of controls were included. We found that CD was an independent risk
      factor for breast cancer development (OR = 2.76, 95% CI = 1.2-6.2; p = 0.017),
      and this is particularly evident in mothers (3.6% vs 1%, p = 0.009 - OR = 3.7,
      95% CI 1.4-10). Among CD group, smoking habit of CD patients was associated with
      increased risk of cancer compared with relatives of non-smokers (7.7% vs 2.9%, p
      = 0.01 - OR = 2.8 95% CI 1.2-6.6). Intriguingly, stage at diagnosis was
      significantly higher in CD relatives (p = 0.04). Our findings suggest that first
      degree female relatives of CD patients are at higher risk of developing breast
      cancer but receive diagnosis at more advanced stages, therefore advocating the
      need of more active screening protocol in this population. 

PMID- 24866078
TI  - TERT promoter mutation in resectable hepatocellular carcinomas: a strong
      association with hepatitis C infection and absence of hepatitis B infection.
AB  - INTRODUCTION: Mutation in the core promoter of the telomerase reverse
      transcriptase (TERT) gene was determined to be a frequent event in malignant
      melanoma and other cancers. However, the role of TERT promoter mutation in
      hepatocellular carcinomas (HCCs) remains largely unknown. METHODS: Genomic DNA
      samples from the tumor tissue of 195 HCCs were analyzed for TERT promoter
      mutation at 2 hotspots (-124 and -146 bp from the ATG start site, g.1,295,228 and
      g.1,295,250, respectively) through direct sequencing. RESULTS: The TERT promoter
      mutation was identified in 57 of the 195 HCCs (29.2%) and was associated with old
      age (P = 0.0122), presence of anti-hepatitis C (HCV; P = 0.0048), and absence of
      hepatitis B surface antigen (HBsAg; P = 0.0007). However, the TERT promoter
      mutation did not correlate with serum alpha-fetoprotein levels, liver cirrhosis,
      tumor size, tumor grade, tumor stage, early tumor recurrence, beta-catenin
      mutation or p53 mutation. A multivariate analysis confirmed that the absence of
      hepatitis B infection is an independent factor associated with TERT promoter
      mutation. Furthermore, among HCC patients infected with hepatitis C, those with
      concomitant hepatitis B infection exhibited infrequent TERT promoter mutation (P
      = 0.0435). Remarkably, patients presenting with TERT promoter mutation-positive
      and -negative HCCs exhibited similar disease-free and overall survival rates.
      CONCLUSIONS: Our study indicated that the TERT promoter mutation frequently
      occurred in HCV-associated HCCs. The absence of Hepatitis B infection was
      significantly associated with the TERT promoter mutation. These findings suggest
      that various etiological factors may be involved in differing mechanisms to
      preserve telomeres during the carcinogenesis of HCCs.

PMID- 24866079
TI  - An evidence-based appraisal of global association between air pollution and risk
      of stroke.
AB  - BACKGROUND: The aim of this study was to evaluate the transient effects of air
      pollutants on stroke morbidity and mortality using the meta-analytic approach.
      METHODS: Three databases were searched for case-crossover and time series studies
      assessing associations between daily increases in particles with diameter<2.5 MUm
      (PM2.5) and diameter<10 MUm (PM10), sulfur dioxide (SO2), carbon monoxide (CO),
      nitrogen dioxide (NO2), ozone, and risks of stroke hospitalizations and
      mortality. Risk estimates were combined using random-effects model. RESULTS: A
      total of 34 studies were included in the meta-analysis. Stroke hospitalizations
      or mortality increased 1.20% (95%CI: 0.22-2.18) per 10 MUg/m3 increase in PM2.5,
      0.58% (95%CI: 0.31-0.86) per 10 MUg/m3 increase in PM10, 1.53% (95%CI: 0.66-2.41)
      per 10 parts per billion (ppb) increase in SO2, 2.96% (95%CI: 0.70-5.27) per 1
      ppm increase in CO, and 2.24% (95%CI: 1.16-3.33) per 10ppb increase in NO2. These
      positive associations were the strongest on the same day of exposure, and
      appeared to be more apparent for ischemic stroke (for all 4 gaseous pollutants)
      and among Asian countries (for all 6 pollutants). In addition, an elevated risk
      (2.45% per 10 ppb; 95%CI: 0.35-4.60) of ischemic stroke associated with ozone was
      found, but not for hemorrhagic stroke. CONCLUSION: Our study indicates that air
      pollution may transiently increase the risk of stroke hospitalizations and stroke
      mortality. Although with a weak association, these findings if validated may be
      of both clinical and public health importance given the great global burden of
      stroke and air pollution.

PMID- 24866080
TI  - Ear lobe crease as a marker of coronary artery disease: a meta-analysis.

PMID- 24866081
TI  - A proposal for a diagnostic index for the differentiation between Takotsubo
      syndrome and acute coronary syndromes.

PMID- 24866082
TI  - A molecular modeling study of the changes of some steric properties of the
      precatalysts during the olefin metathesis reaction.
AB  - The productive self-metathesis of 1-octene with a series of new phosphine ligated
      Grubbs-type precatalysts was studied. The resulting structures were used to
      compare some steric properties of the new precatalysts with those of well-known
      precatalysts. The possibility of alpha-CC agnostic stabilization as well as the
      ability of the ligands to shield the metal was studied. A comparison of the
      obtained data, pointed to the unlikelihood that alpha-CC agostic stabilization is
      a major contribution to the stabilization of the various metallacyclobutane
      rings. The similarity in the ability of the ligands to shield the metal also
      raised questions about the comparison of experimentally observed trends with
      those obtained theoretically.

PMID- 24866083
TI  - Short communication: Prevalence and risk factors for human T cell lymphotropic
      virus infection in Southern Brazilian HIV-positive patients.
AB  - HIV/human T cell lymphotropic virus (HTLV) coinfection has a large range of
      prevalence in the different risk groups and geographic regions of the world. Most
      of the HTLV-infected people live in geographic areas where the virus is endemic,
      as it happens in Brazil. The aim of this study was to identify HTLV prevalence
      and risk factors in HIV-positive patients. A cross-sectional study was conducted
      with 580 HIV-positive patients (mean age of 40.6 years and 45.0% men) from a
      specialized HIV/AIDS diagnosis and treatment center in Southern Brazil.
      Sociodemographic data, HIV risk factors, and HTLV-1/2 antibodies were collected.
      HTLV proviral DNA was detected by polymerase chain reaction (PCR). A multivariate
      analysis was performed to identify risk factors for HTLV infection. HTLV
      antibodies were detected in 29 (5.0%) and HTLV provirus in 17 (2.9%) patients.
      HTLV-1 was identified in 11 (64.7%) patients and HTLV-2 in 6 (35.3%) patients. No
      significant differences were observed between mono and coinfected patients in
      clinical characteristics regarding HIV/AIDS (time since HIV diagnosis, HIV viral
      load, lymphocytes CD4(+) count, and use of highly active antiretroviral therapy).
      Blood transfusion history was significantly associated with HIV/HTLV coinfection
      (p=0.039). Alcohol abuse was more prevalent in HTLV-positive (47.1%) than in HIV
      mono-infected patients (20.4%; p=0.008). Tattooing was the only risk factor
      independently associated with HIV/HTLV coinfection (p=0.035). This information
      contributes to an understanding of the epidemiology of HIV/HTLV coinfection in
      Brazil.

PMID- 24866084
TI  - Systematic review of instruments for measuring nurses' knowledge, skills and
      attitudes for evidence-based practice.
AB  - AIM: To identify, appraise and describe the characteristics of instruments for
      measuring evidence-based knowledge, skills and/or attitudes in nursing practice.
      BACKGROUND: Evidence-based practice has been proposed for optimal patient care
      for more than three decades, yet competence in evidence-based practice knowledge
      and skills among nurse clinicians remains difficult to measure. There is a need
      to identify well-validated and reliable instruments for assessing competence for
      evidence-based practice in nursing. DESIGN: Psychometric systematic review. DATA
      SOURCES: The MEDLINE, EMBASE, CINAHL, ERIC, CDSR, All EBM reviews and PsycInfo
      databases were searched from 1960-April 2013; with no language restrictions
      applied. REVIEW METHODS: Using pre-determined inclusion criteria, three reviewers
      independently identified studies for full-text review, extracting data and
      grading instrument validity using a Psychometric Grading Framework. RESULTS: Of
      91 studies identified for full-text review, 59 met the inclusion criteria
      representing 24 different instruments. The Psychometric Grading Framework
      determined that only two instruments had adequate validity - the Evidence Based
      Practice Questionnaire measuring knowledge, skills and attitudes and another un
      named instrument measuring only EBP knowledge and attitudes. Instruments used in
      another nine studies were graded as having 'weak' validity and instruments in the
      remaining 24 studies were graded as 'very weak'. CONCLUSION: The Evidence Based
      Practice Questionnaire was assessed as having the highest validity and was the
      most practical instrument to use. However, the Evidence Based Practice
      Questionnaire relies totally on self-report rather than direct measurement of
      competence suggesting a need for a performance-based instrument for measuring
      evidence-based knowledge, skills and attitudes in nursing.

PMID- 24866085
TI  - A selectively rhodamine-based colorimetric probe for detecting copper(II) ion.
AB  - A novel rhodamine derivative 3-bromo-5-methylsalicylaldehyde rhodamine B
      hydrazone (BMSRH) has been synthesized by reacting rhodamine B hydrazide with 3
      bromo-5-methylsalicylaldehyde and developed as a new colorimetric probe for the
      selective and sensitive detection of Cu2+. Addition of Cu2+ to the solution of
      BMSRH results in a rapid color change from colorless to red together with an
      obvious new band appeared at 552 nm in the UV-vis absorption spectra. This change
      is attributed to the spirocycle form of BMSRH opened via coordination with Cu2+
      in a 1:1 stoichiometry and their association constant is determined as 3.2*10(4)
      L mol(-1). Experimental results indicate that the BMSRH can provide a rapid,
      selective and sensitive response to Cu2+ with a linear dynamic range 0.667-240
      MUmol/L. Common interferent ions do not show any interference on the Cu2+
      determination. It is anticipated that BMSRH can be a good candidate probe and has
      potential application for Cu2+ determination. The proposed probe exhibits the
      following advantages: a quick, simple and facile synthesis.

PMID- 24866086
TI  - In vitro studies on the behavior of salmeterol xinafoate and its interaction with
      calf thymus DNA by multi-spectroscopic techniques.
AB  - The salmeterol xinafoate (SX) binding to calf thymus DNA in vitro was explored by
      fluorescence, resonance light scattering (RLS), UV-vis absorption, as well as
      viscometry, ionic strength effect and DNA melting techniques. It was found that
      SX could bind to DNA weakly, and the binding constants (Ka) were determined as
      8.52*10(3), 8.31*10(3) and 6.14*10(3) L mol(-1) at 18, 28 and 38 degrees C
      respectively. When bound to DNA, SX showed fluorescence quenching in the
      fluorescence spectra and hyperchromic effect in the absorption spectra. Stern
      Volmer plots revealed that the quenching of fluorescence of SX by DNA was a
      static quenching. Furthermore, the relative viscosity and melting temperature of
      DNA solution were hardly influenced by SX, while the fluorescence intensity of SX
      DNA was observed to decrease with the increasing ionic strength of system. Also,
      the binding constant between SX and double stranded DNA (dsDNA) was much weaker
      than that between SX and single stranded DNA (ssDNA). All these results suggested
      that the binding mode of SX to DNA should be groove binding. The obtained
      thermodynamic parameters indicated that electrostatic force might play a
      predominant role in SX binding to DNA. The quantum yield (phi) of SX was measured
      as 0.13 using comparative method. Based on the Forster resonance energy transfer
      theory (FRET), the binding distance (r0) between the acceptor and donor was
      calculated as 4.10 nm.

PMID- 24866087
TI  - Temperature-dependent self-assembly of near-infrared (NIR) luminescent Zn2Ln and
      Zn2Ln3 (Ln=Nd, Yb or Er) complexes from the flexible Salen-type Schiff-base
      ligand.
AB  - Through the self-assembly of the precursor [Zn(L)(MeCN)] (H2L=N,N'-bis(3-methoxy
      salicylidene)cyclohexane-1,2-diamine) with LnCl3.6H2O (Ln=La, Nd, Yb, Er or Gd)
      and NaN3 in alcohol-containing solutions, two series of mixed anions-induced
      Zn2Ln-arrayed complexes [Zn2(L)2(MeOH)ClLn(N3)].Cl (Ln=La, 1; Ln=Nd, 2; Ln=Yb, 3;
      Ln=Er, 4 or Ln=Gd, 5) and Zn2Ln3-arrayed complexes [Zn2(L)3Cl2(MU2-OH)(MU3
      OH)2Ln3(N3)2] (Ln=La, 6; Ln=Nd, 7; Ln=Yb, 8; Ln=Er, 9 or Ln=Gd, 10) are obtained
      at room temperature or under reflux, respectively. In contrast to Zn2Ln-arrayed
      complexes with the two Zn2+ ions in the inner cis-N2O2 cores and one Ln3+ ion in
      the outer O2O2 moieties, the demetalation of partial precursors leads to the
      selective exchange of Zn2+ centers for the Ln3+ ions for the formation of novel
      heterometallic Zn2Ln3-arrayed complexes with the Ln3+ ions in both the inner cis
      N2O2 core and the outer O2O2 moieties of the ligands. The result of their
      photophysical properties shows that the characteristic near-infrared (NIR)
      luminescence of Nd3+ or Yb3+ ion has been sensitized from the excited state (both
      1LC and 3LC) of the ligand H2L, while relatively lower quantum yields for Zn2Ln3
      arrayed complexes than those for Zn2Ln-arrayed complexes, correspondingly, should
      be due to the luminescent quenching with the involvement of OH- oscillators
      around the Ln3+ ions.

PMID- 24866088
TI  - The study of secondary effects in vibrational and hydrogen bonding properties of
      2- and 3-ethynylpyridine and ethynylbenzene by IR spectroscopy.
AB  - Weak hydrogen bonds formed by 2- and 3-ethynylpyridine and ethynylbenzene with
      trimethylphosphate and phenol were characterized by IR spectroscopy and DFT
      calculations (B3LYP/6-311++G(d, p)). The structure and stability of
      ethynylpyridines and ethynylbenzene in the gas phase and in the complexes with
      trimethylphosphate and phenol are discussed in terms of geometry and electronic
      charge redistribution. Anharmonic effects are taken into account when calculating
      vibrational wavenumbers of these systems what lead to partial improvement of
      agreement with experiment. The changes in the electronic charge distribution are
      behind the frequency shifts of the CC stretching in opposite direction depending
      on the role the ethyne molecule has in a hydrogen bonded complex (Deltanu=+9 cm(
      1) in trimethylphosphate complexes, Deltanu=-3 cm(-1) in phenol complexes). The
      association constants were determined by keeping the concentrations of proton
      donors approximately constant and low enough to avoid self-association and the
      proton acceptors were present in excess. The values obtained for the association
      constants and enthalpy changes in C2Cl4 (for trimethylphosphate complexes K~0.5
      1.0 mol(-1)dm(3) and -DeltarH~6-8 kJ mol(-1), for phenol complexes K~20-40 mol(
      1) dm3-DeltarH~17-22 kJ mol(-1)) are in good agreement with literature data.

PMID- 24866089
TI  - Infrared and Raman spectroscopic studies of tris-[3-(trimethoxysilyl)propyl]
      isocyanurate, its sol-gel process, and coating on aluminum and copper.
AB  - Tris-[3-(trimethoxysilyl)propyl] isocyanurate (TTPI) has been used as a precursor
      to prepare a sol using ethanol as the solvent under acidic conditions. The sol
      gel was applied for the surface treatment of aluminum and copper. Infrared and
      Raman spectra have been recorded for pure TTPI and the TTPI sol, xerogel and TTPI
      sol-gel coated metals. From the vibrational spectra, TTPI is likely to have the
      C1 point group. Vibrational assignments are suggested based on group frequencies,
      the expected reactions in the sol-gel process and the vibrational studies of some
      related molecules. From the experimental infrared spectra of xerogels annealed at
      different temperatures and from the thermal-gravimetric analysis, it is found
      that the TTPI xerogel decomposes at around 450 degrees C with silica being the
      major decomposition product. A cyclic voltammetric study of the metal electrodes
      coated with different concentrations of TTPI ranging from 5% to 42% (v/v) has
      shown that the films with high concentrations of sol would provide better
      corrosion protection for aluminum and copper. 

PMID- 24866090
TI  - Theoretical design of thiazolothiazole-based organic dyes with different electron
      donors for dye-sensitized solar cells.
AB  - In this study, we have designed four novel organic donor-pi-acceptor dyes (D1,
      D2, D3, D4), used for dye sensitized solar cells (DSSCs). The electron acceptor
      (anchoring) group was 2-cyanoacrylic for all dyes whereas the electron donor unit
      varied (coumarin, indoline, carbazole, triphenylamine) and the influence was
      investigated. These dyes, based on thiazolothiazole as pi-spacer, were studied by
      density functional theory (DFT) and its extensible time dependant DFT (TDDFT)
      approaches to shed light on how the pi-conjugation order influence the
      performance of the dyes in the DSSCs. The theoretical results have shown that the
      LUMO and HOMO energy levels of these dyes can be ensuring positive effect on the
      process of electron injection and dye regeneration. The trend of the calculated
      HOMO-LUMO gaps nicely compares with the spectral data. Key parameters in close
      connection with the short-circuit current density (Jsc), including light
      harvesting efficiency (LHE), injection driving force (DeltaGinject.) and total
      reorganization energy (lambdatotal), were discussed. The calculated results of
      these dyes reveal that dye D2, with indoline as electron donor group, can be used
      as a potential sensitizer for TiO2 nanocrystalline solar cells due to its best
      electronic and optical properties and good photovoltaic parameters.

PMID- 24866091
TI  - Novel ureteroscopic navigation system with a magnetic tracking device: a
      preliminary ex vivo evaluation.
AB  - PURPOSE: Examination of the pyelocaliceal system using a flexible ureteroscope
      necessitates accurate orientation of the tip of the instrument. This study
      assessed the use of a novel real-time ureteroscopic navigation system in a
      pyelocaliceal phantom. MATERIALS AND METHODS: The navigation system used a
      magnetic tracking device to determine the position of the ureteroscope in a
      pyelocaliceal phantom and displayed the position of the endoscope on a three
      dimensional image that could be rotated. Twenty-eight urologists were divided
      into group A and group B (seven novice surgeons and seven experienced surgeons in
      each group). All participants were asked to examine the phantom and identify the
      positions of three designated calices, without the navigation system (Task 1) and
      with the navigation system (Task 2). In group A, participants performed Task 1
      followed by Task 2. In group B, participants performed Task 2 followed by Task 1.
      The accuracy rate (AR) of identifying the calices, migration length (ML) of the
      tip of the ureteroscope, and time (T) taken to complete the task were recorded.
      The results were compared between Task 1 and Task 2, and between novice and
      experienced surgeons. RESULTS: The AR for Task 2 was 100% in both group A and
      group B. The AR was significantly lower in Task 1 than in Task 2 for both novice
      and experienced surgeons in both groups (group A: novice P=0.016, experienced
      P=0.034; group B: novice P=0.015, experienced P=0.015; Wilcoxon test). In Group
      A, T was significantly longer in Task 1 than in Task 2 for experienced surgeons.
      There were no significant differences in ML or T between novice and experienced
      surgeons. CONCLUSIONS: Our novel ureteroscopic navigation system improved the
      accuracy of ureteroscopic maneuvers. Further development of this system for use
      in clinical ureteroscopic procedures is planned.

PMID- 24866092
TI  - Xanthomonas campestris RpfB is a fatty Acyl-CoA ligase required to counteract the
      thioesterase activity of the RpfF diffusible signal factor (DSF) synthase.
AB  - In Xanthomonas campestris pv. campestris (Xcc), the proteins encoded by the rpf
      (regulator of pathogenicity factor) gene cluster produce and sense a fatty acid
      signal molecule called diffusible signalling factor (DSF, 2(Z)-11
      methyldodecenoic acid). RpfB was reported to be involved in DSF processing and
      was predicted to encode an acyl-CoA ligase. We report that RpfB activates a wide
      range of fatty acids to their CoA esters in vitro. Moreover, RpfB can
      functionally replace the paradigm bacterial acyl-CoA ligase, Escherichia coli
      FadD, in the E. coli beta-oxidation pathway and deletion of RpfB from the Xcc
      genome results in a strain unable to utilize fatty acids as carbon sources. An
      essential RpfB function in the pathogenicity factor pathway was demonstrated by
      the properties of a strain deleted for both the rpfB and rpfC genes. The
      DeltarpfB DeltarpfC strain grew poorly and lysed upon entering stationary phase.
      Deletion of rpfF, the gene encoding the DSF synthetic enzyme, restored normal
      growth to this strain. RpfF is a dual function enzyme that synthesizes DSF by
      dehydration of a 3-hydroxyacyl-acyl carrier protein (ACP) fatty acid synthetic
      intermediate and also cleaves the thioester bond linking DSF to ACP. However, the
      RpfF thioesterase activity is of broad specificity and upon elimination of its
      RpfC inhibitor RpfF attains maximal activity and its thioesterase activity
      proceeds to block membrane lipid synthesis by cleavage of acyl-ACP intermediates.
      This resulted in release of the nascent acyl chains to the medium as free fatty
      acids. This lack of acyl chains for phospholipid synthesis results in cell lysis
      unless RpfB is present to counteract the RpfF thioesterase activity by catalysing
      uptake and activation of the free fatty acids to give acyl-CoAs that can be
      utilized to restore membrane lipid synthesis. Heterologous expression of a
      different fatty acid activating enzyme, the Vibrio harveyi acyl-ACP synthetase,
      replaced RpfB in counteracting the effects of high level RpfF thioesterase
      activity indicating that the essential role of RpfB is uptake and activation of
      free fatty acids. 

PMID- 24866095
TI  - Human polyomavirus 9 infection in kidney transplant patients.
AB  - Several human polyomaviruses of unknown prevalence and pathogenicity have been
      identified, including human polyomavirus 9 (HPyV9). To determine rates of HPyV9
      infection among immunosuppressed patients, we screened serum samples from 101
      kidney transplant patients in the Netherlands for HPyV9 DNA and seroreactivity. A
      total of 21 patients had positive results for HPyV9 DNA; positivity rates peaked
      at 3 months after transplantation, but the highest viral loads were measured just
      after transplantation. During 18 months of follow-up, HPyV9 seroprevalence
      increased from 33% to 46% among transplant patients; seroprevalence remained
      stable at ~30% in a control group of healthy blood donors in whom no HPyV9 DNA
      was detected. Further analysis revealed an association between detection of HPyV9
      and detection of BK polyomavirus but not of cytomegalovirus. Our data indicate
      that HPyV9 infection is frequent in kidney transplant patients, but the nature of
      infection-endogenous or donor-derived-and pathogenic potential of this virus
      remain unknown. 

PMID- 24866096
TI  - Direct alkalinity detection with ion-selective chronopotentiometry.
AB  - We explore the possibility to directly measure pH and alkalinity in the sample
      with the same sensor by imposing an outward flux of hydrogen ions from an ion
      selective membrane to the sample solution by an applied current. The membrane
      consists of a polypropylene-supported liquid membrane doped with a hydrogen
      ionophore (chromoionophore I), ion exchanger (KTFBP), and lipophilic electrolyte
      (ETH 500). While the sample pH is measured at zero current, alkalinity is
      assessed by chronopotentiometry at anodic current. Hydrogen ions expelled from
      the membrane undergo acid-base solution chemistry and protonate available base in
      the diffusion layer. With time, base species start to be depleted owing to the
      constant imposed hydrogen ion flux from the membrane, and a local pH change
      occurs at a transition time. This pH change (potential readout) is correlated to
      the concentration of the base in solution. As in traditional chronopotentiometry,
      the observed square root of transition time (tau) was found to be linear in the
      concentration range of 0.1 mM to 1 mM, using the bases
      tris(hydroxymethyl)aminomethane, ammonia, carbonate, hydroxide, hydrogen
      phosphate, and borate. Numerical simulations were used to predict the
      concentration profiles and the chronopotentiograms, allowing the discussion of
      possible limitations of the proposed method and its comparison with volumetric
      titrations of alkalinity. Finally, the P-alkalinity level is measured in a river
      sample to demonstrate the analytical usefulness of the proposed method. As a
      result of these preliminary results, we believe that this approach may become
      useful for the in situ determination of P-alkalinity in a range of matrixes. 

PMID- 24866101
TI  - Carbonylations of alkenes with CO surrogates.
AB  - Alkene carbonylation reactions are important for the production of value-added
      bulk and fine chemicals. Nowadays, all industrial carbonylation processes make
      use of highly toxic and flammable carbon monoxide. In fact, these properties
      impede the wider use of carbonylation reactions in industry and academia. Hence,
      performing carbonylations without the use of CO is highly desired and will
      contribute to the further advancement of sustainable chemistry. Although the use
      of carbon monoxide surrogates in alkene carbonylation reactions has been reported
      intermittently in the last 30 years, only recently has this area attracted
      significant interest. This Minireview summarizes carbonylation reactions of
      alkenes using different carbon monoxide surrogates.

PMID- 24866102
TI  - [Retraction] Generation of induced pluripotent stem cells using skin fibroblasts
      from patients with myocardial infarction under feeder-free conditions.
AB  - After the publication of the article, the authors decided they wished to retract
      their manuscript for the following reasons. We wish to retract our research
      article entitled 'Generation of induced pluripotent stem cells using skin
      fibroblasts from patients with myocardial infarction under feeder-free
      conditions' published on the Molecular Medicine Reports 9: 837-842, 2014. In this
      article, we generated human iPSCs from skin fibroblasts from myocardial
      infarction patients in feeder-independent conditions. However, in subsequent
      researches, all of the cells generated and believed to be iPSCs showed negative
      expression of the pluripotent markers, Nanog and Rex1, and the cell surface
      marker, SSEA-1 and SSEA-4. Therefore we think the established iPS cells might not
      be real pluripotent stem cells. Based on the above mentioned, we ascertained that
      there must have some serious disadvantages in our design of experiment
      fundamentally. As a result, all authors involved unanimously agreed to retract
      this article and redesign our experiment. We deeply apologize to the readers for
      any inconvenience caused by this retraction. [the original article was published
      in the Molecular Medicine Reports 9: 837-842, 2014 DOI: 10.3892/mmr.2014.1885]. 

PMID- 24866104
TI  - Gaze and visual search strategies of children with Asperger syndrome/high
      functioning autism viewing a magic trick.
AB  - OBJECTIVE: To examine visual search patterns and strategies used by children with
      and without Asperger syndrome/high functioning autism (AS/HFA) while watching a
      magic trick. Limited responsivity to gaze cues is hypothesised to contribute to
      social deficits in children with AS/HFA. METHODS: Twenty-one children with AS/HFA
      and 31 matched peers viewed a video of a gaze-cued magic trick twice. Between the
      viewings, they were informed about how the trick was performed. Participants' eye
      movements were recorded using a head-mounted eye-tracker. RESULTS: Children with
      AS/HFA looked less frequently and had shorter fixation on the magician's direct
      and averted gazes during both viewings and more frequently at not gaze-cued
      objects and on areas outside the magician's face. After being informed of how the
      trick was conducted, both groups made fewer fixations on gaze-cued objects and
      direct gaze. CONCLUSIONS: Information may enhance effective visual strategies in
      children with and without AS/HFA.

PMID- 24866103
TI  - The relationship between area poverty rate and site-specific cancer incidence in
      the United States.
AB  - BACKGROUND: The relationship between socioeconomic status and cancer incidence in
      the United States has not traditionally been a focus of population-based cancer
      surveillance systems. METHODS: Nearly 3 million tumors diagnosed between 2005 and
      2009 from 16 states plus Los Angeles were assigned into 1 of 4 groupings based on
      the poverty rate of the residential census tract at time of diagnosis. The sex
      specific risk ratio of the highest-to-lowest poverty category was measured using
      Poisson regression, adjusting for age and race, for 39 cancer sites. RESULTS: For
      all sites combined, there was a negligible association between cancer incidence
      and poverty; however, 32 of 39 cancer sites showed a significant association with
      poverty (14 positively associated and 18 negatively associated). Nineteen of
      these sites had monotonic increases or decreases in risk across all 4 poverty
      categories. The sites most strongly associated with higher poverty were Kaposi
      sarcoma, larynx, cervix, penis, and liver; those most strongly associated with
      lower poverty were melanoma, thyroid, other nonepithelial skin, and testis. Sites
      associated with higher poverty had lower incidence and higher mortality than
      those associated with lower poverty. CONCLUSIONS: These findings demonstrate the
      importance and relevance of including a measure of socioeconomic status in
      national cancer surveillance. Cancer 2014;120:2191-2198. (c) 2014 The Authors.
      Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

PMID- 24866099
TI  - Activation of sodium-dependent glutamate transporters regulates the morphological
      aspects of oligodendrocyte maturation via signaling through calcium/calmodulin
      dependent kinase IIbeta's actin-binding/-stabilizing domain.
AB  - Signaling via the major excitatory amino acid glutamate has been implicated in
      the regulation of various aspects of the biology of oligodendrocytes, the
      myelinating cells of the central nervous system (CNS). In this respect, cells of
      the oligodendrocyte lineage have been described to express a variety of glutamate
      responsive transmembrane proteins including sodium-dependent glutamate
      transporters. The latter have been well characterized to mediate glutamate
      clearance from the extracellular space. However, there is increasing evidence
      that they also mediate glutamate-induced intracellular signaling events. Our data
      presented here show that the activation of oligodendrocyte expressed sodium
      dependent glutamate transporters, in particular GLT-1 and GLAST, promotes the
      morphological aspects of oligodendrocyte maturation. This effect was found to be
      associated with a transient increase in intracellular calcium levels and a
      transient phosphorylation event at the serine (S)(371) site of the calcium sensor
      calcium/calmodulin-dependent kinase type IIbeta (CaMKIIbeta). The potential
      regulatory S(371) site is located within CaMKIIbeta's previously defined actin
      binding/-stabilizing domain, and phosphorylation events within this domain were
      identified in our studies as a requirement for sodium-dependent glutamate
      transporter-mediated promotion of oligodendrocyte maturation. Furthermore, our
      data provide good evidence for a role of these phosphorylation events in
      mediating detachment of CaMKIIbeta from filamentous (F)-actin, and hence allowing
      a remodeling of the oligodendrocyte's actin cytoskeleton. Taken together with our
      recent findings, which demonstrated a crucial role of CaMKIIbeta in regulating
      CNS myelination in vivo, our data strongly suggest that a sodium-dependent
      glutamate transporter-CaMKIIbeta-actin cytoskeleton axis plays an important role
      in the regulation of oligodendrocyte maturation and CNS myelination.

PMID- 24866105
TI  - Graphene transistors with multifunctional polymer brushes for biosensing
      applications.
AB  - Exhibiting a combination of exceptional structural and electronic properties,
      graphene has a great potential for the development of highly sensitive sensors.
      To date, many challenging chemical, biochemical, and biologic sensing tasks have
      been realized based on graphene. However, many of these sensors are rather
      unspecific. To overcome this problem, for instance, the sensor surface can be
      modified with analyte-specific transducers such as enzymes. One problem
      associated with the covalent attachment of such biomolecular systems is the
      introduction of crystal defects that have a deleterious impact on the electronic
      properties of the sensor. In this work, we present a versatile platform for
      biosensing applications based on polymer-modified CVD-grown graphene transistors.
      The functionalization method of graphene presented here allows one to integrate
      several functional groups within surface-bound polymer brushes without the
      introduction of additional defects. To demonstrate the potential of this polymer
      brush functionalization scaffold, we modified solution-gated graphene field
      effect transistors with the enzyme acetylcholinesterase and a transducing group,
      allowing the detection of the neurotransmitter acetylcholine. Taking advantage of
      the transducing capability of graphene transistors and the versatility of polymer
      chemistry and enzyme biochemistry, this study presents a novel route for the
      fabrication of highly sensitive, multipurpose transistor sensors that can find
      application for a multitude of biologically relevant analytes. 

PMID- 24866111
TI  - Stretching and folding of 2-nanometer hydrocarbon rods.
AB  - Linear alkanes CnH2n+2 in vacuum isolation are finite models for an infinite
      polyethylene chain. Using spontaneous Raman scattering in supersonic jet
      expansions for n = 13-21 in different spectral ranges, we determine the minimal
      chain length nh for the cohesion-driven folding of the preferred extended all
      trans conformation into a hairpin structure. We treat fully stretched all-trans
      alkanes as molecular "nanorods" and derive Young's modulus E for the stretching
      of an isolated single-strand polyethylene fibre by extrapolating the longitudinal
      acoustic mode to infinite chain length. Two key quality parameters for accurate
      intra- and intermolecular force fields of hydrocarbons (nh = 18 +/- 1, E = 305 +/
      5 GPa) are thus derived with high accuracy from experimental spectroscopy. 

PMID- 24866108
TI  - Evaluation of cardiovascular parameters in cynomolgus monkeys following IV
      administration of LBR-101, a monoclonal antibody against calcitonin gene-related
      peptide.
AB  - Calcitonin gene-related peptide (CGRP) is a well-validated target for migraine
      therapy and a known potent systemic vasodilator. LBR-101 is a monoclonal antibody
      against CGRP in clinical development for the preventive treatment of episodic and
      chronic migraine. Understanding the hemodynamic and cardiovascular consequences
      of chronic CGRP inhibition is therefore warranted. Given the conservation in CGRP
      sequence between monkeys and humans, addressing this question in monkeys is ideal
      as it allows dosing at super-therapeutic levels. To this end, two independent
      studies were conducted in monkeys: a single dedicated cardiovascular safety study
      and a repeat-dose, chronic study, both with electrocardiogram and hemodynamic
      assessments. LBR-101 was very well tolerated in both studies, with no clinically
      significant changes noted in any hemodynamic parameter, nor any relevant changes
      noted in any ECG parameter. In cynomolgus monkeys, cardiovascular and hemodynamic
      parameters do not appear to be affected by long-term inhibition of CGRP with LBR
      101. 

PMID- 24866112
TI  - Transcription factor heterogeneity in pluripotent stem cells: a stochastic
      advantage.
AB  - When pluripotent cells are exposed to a uniform culture environment they
      routinely display heterogeneous gene expression. Aspects of this heterogeneity,
      such as Nanog expression, are linked to differences in the propensity of
      individual cells to either self-renew or commit towards differentiation. Recent
      findings have provided new insight into the underlying causes of this
      heterogeneity, which we summarise here using Nanog, a key regulator of
      pluripotency, as a model gene. We discuss the role of transcription factor
      heterogeneity in facilitating the intrinsically dynamic and stochastic nature of
      the pluripotency network, which in turn provides a potential benefit to a
      population of cells that needs to balance cell fate decisions. 

PMID- 24866113
TI  - Neural progenitors, neurogenesis and the evolution of the neocortex.
AB  - The neocortex is the seat of higher cognitive functions and, in evolutionary
      terms, is the youngest part of the mammalian brain. Since its origin, the
      neocortex has expanded in several mammalian lineages, and this is particularly
      notable in humans. This expansion reflects an increase in the number of
      neocortical neurons, which is determined during development and primarily
      reflects the number of neurogenic divisions of distinct classes of neural
      progenitor cells. Consequently, the evolutionary expansion of the neocortex and
      the concomitant increase in the numbers of neurons produced during development
      entail interspecies differences in neural progenitor biology. Here, we review the
      diversity of neocortical neural progenitors, their interspecies variations and
      their roles in determining the evolutionary increase in neuron numbers and
      neocortex size. 

PMID- 24866115
TI  - Identification and characterization of putative stem cells in the adult pig
      ovary.
AB  - Recently, the concept of 'neo-oogenesis' has received increasing attention, since
      it was shown that adult mammals have a renewable source of eggs. The purpose of
      this study was to elucidate the origin of these eggs and to confirm whether neo
      oogenesis continues throughout life in the ovaries of the adult mammal. Adult
      female pigs were utilized to isolate, identify and characterize, including their
      proliferation and differentiation capabilities, putative stem cells (PSCs) from
      the ovary. PSCs were found to comprise a heterogeneous population based on c-kit
      expression and cell size, and also express stem and germ cell markers. Analysis
      of PSC molecular progression during establishment showed that these cells undergo
      cytoplasmic-to-nuclear translocation of Oct4 in a manner reminiscent of gonadal
      primordial germ cells (PGCs). Hence, cells with the characteristics of early PGCs
      are present or are generated in the adult pig ovary. Furthermore, the in vitro
      establishment of porcine PSCs required the presence of ovarian cell-derived
      extracellular regulatory factors, which are also likely to direct stem cell niche
      interactions in vivo. In conclusion, the present work supports a crucial role for
      c-kit and kit ligand/stem cell factor in stimulating the growth, proliferation
      and nuclear reprogramming of porcine PSCs, and further suggests that porcine PSCs
      might be the culture equivalent of early PGCs. 

PMID- 24866114
TI  - Switching on sex: transcriptional regulation of the testis-determining gene Sry.
AB  - Mammalian sex determination hinges on the development of ovaries or testes, with
      testis fate being triggered by the expression of the transcription factor sex
      determining region Y (Sry). Reduced or delayed Sry expression impairs testis
      development, highlighting the importance of its accurate spatiotemporal
      regulation and implying a potential role for SRY dysregulation in human intersex
      disorders. Several epigenetic modifiers, transcription factors and kinases are
      implicated in regulating Sry transcription, but it remains unclear whether or how
      this farrago of factors acts co-ordinately. Here we review our current
      understanding of Sry regulation and provide a model that assembles all known
      regulators into three modules, each converging on a single transcription factor
      that binds to the Sry promoter. We also discuss potential future avenues for
      discovering the cis-elements and trans-factors required for Sry regulation. 

PMID- 24866118
TI  - Dynamic clonal analysis based on chronic in vivo imaging allows multiscale
      quantification of growth in the Drosophila wing disc.
AB  - In the course of morphogenesis, tissues change shape and grow. How this is
      orchestrated is largely unknown, partly owing to the lack of experimental methods
      to visualize and quantify growth. Here, we describe a novel experimental approach
      to investigate the growth of tissues in vivo on a time-scale of days, as employed
      to study the Drosophila larval imaginal wing disc, the precursor of the adult
      wing. We developed a protocol to image wing discs at regular intervals in living
      anesthetized larvae so as to follow the growth of the tissue over extended
      periods of time. This approach can be used to image cells at high resolution in
      vivo. At intermediate scale, we tracked the increase in cell number within clones
      as well as the changes in clone area and shape. At scales extending to the tissue
      level, clones can be used as landmarks for measuring strain, as a proxy for
      growth. We developed general computational tools to extract strain maps from
      clonal shapes and landmark displacements in individual tissues, and to combine
      multiple datasets into a mean strain. In the disc, we use these to compare
      properties of growth at the scale of clones (a few cells) and at larger regional
      scales. 

PMID- 24866117
TI  - Limited predictive value of blastomere angle of division in trophectoderm and
      inner cell mass specification.
AB  - The formation of trophectoderm (TE) and pluripotent inner cell mass (ICM) is one
      of the earliest events during mammalian embryogenesis. It is believed that the
      orientation of division of polarised blastomeres in the 8- and 16-cell stage
      embryo determines the fate of daughter cells, based on how asymmetrically
      distributed lineage determinants are segregated. To investigate the relationship
      between angle of division and subsequent fate in unperturbed embryos, we
      constructed cellular resolution digital representations of the development of
      mouse embryos from the morula to early blastocyst stage, based on 4D confocal
      image volumes. We find that at the 16-cell stage, very few inside cells are
      initially produced as a result of cell division, but that the number increases
      due to cell movement. Contrary to expectations, outside cells at the 16-cell
      stage represent a heterogeneous population, with some fated to contributing
      exclusively to the TE and others capable of contributing to both the TE and ICM.
      Our data support the view that factors other than the angle of division, such as
      the position of a blastomere, play a major role in the specification of TE and
      ICM. 

PMID- 24866121
TI  - Effect of cricoid pressure on placement of the I-gelTM : a randomised study.
AB  - We studied 40 adult patients to see if cricoid pressure affected placement of the
      I-gel(TM). In a randomised crossover design, the i-gel was placed with and
      without cricoid pressure, and we compared the success rate of adequate
      ventilation through the i-gel, time to placement and the rate of optimal position
      of the device between the two circumstances. Cricoid pressure significantly
      decreased the success rate of adequate ventilation through the i-gel (40 vs 34
      patients) (p = 0.041, 95% CI for difference 4-26%), and significantly decreased
      the rate of the optimal position (39 vs 17 patients) (p < 0.001). The time to
      achieve adequate ventilation was significantly longer (p < 0.001) with cricoid
      pressure than without (median difference 8 s; 95% CI for median difference 3-12
      s). Cricoid pressure significantly decreases the success rate of ventilation
      through the i-gel, but the success rate of ventilation through the i-gel is
      reasonably high.

PMID- 24866122
TI  - Estimating end-use emissions factors for policy analysis: the case of space
      cooling and heating.
AB  - This paper provides the first estimates of end-use specific emissions factors,
      which are estimates of the amount of a pollutant that is emitted when a unit of
      electricity is generated to meet demand from a specific end-use. In particular,
      this paper provides estimates of emissions factors for space cooling and heating,
      which are two of the most significant end-uses. The analysis is based on a novel
      two-stage regression framework that estimates emissions factors that are specific
      to cooling or heating by exploiting variation in cooling and heating demand
      induced by weather variation. Heating is associated with similar or greater CO2
      emissions factor than cooling in all regions. The difference is greatest in the
      Midwest and Northeast, where the estimated CO2 emissions factor for heating is
      more than 20% larger than the emissions factor for cooling. The minor differences
      in emissions factors in other regions, combined with the substantial difference
      in the demand pattern for cooling and heating, suggests that the use of overall
      regional emissions factors is reasonable for policy evaluations in certain
      locations. Accurately quantifying the emissions factors associated with different
      end-uses across regions will aid in designing improved energy and environmental
      policies. 

PMID- 24866123
TI  - Maximal sum of metabolic exchange fluxes outperforms biomass yield as a predictor
      of growth rate of microorganisms.
AB  - Growth rate has long been considered one of the most valuable phenotypes that can
      be measured in cells. Aside from being highly accessible and informative in
      laboratory cultures, maximal growth rate is often a prime determinant of cellular
      fitness, and predicting phenotypes that underlie fitness is key to both
      understanding and manipulating life. Despite this, current methods for predicting
      microbial fitness typically focus on yields [e.g., predictions of biomass yield
      using GEnome-scale metabolic Models (GEMs)] or notably require many empirical
      kinetic constants or substrate uptake rates, which render these methods
      ineffective in cases where fitness derives most directly from growth rate. Here
      we present a new method for predicting cellular growth rate, termed SUMEX, which
      does not require any empirical variables apart from a metabolic network (i.e., a
      GEM) and the growth medium. SUMEX is calculated by maximizing the SUM of molar
      EXchange fluxes (hence SUMEX) in a genome-scale metabolic model. SUMEX
      successfully predicts relative microbial growth rates across species,
      environments, and genetic conditions, outperforming traditional cellular
      objectives (most notably, the convention assuming biomass maximization). The
      success of SUMEX suggests that the ability of a cell to catabolize substrates and
      produce a strong proton gradient enables fast cell growth. Easily applicable
      heuristics for predicting growth rate, such as what we demonstrate with SUMEX,
      may contribute to numerous medical and biotechnological goals, ranging from the
      engineering of faster-growing industrial strains, modeling of mixed ecological
      communities, and the inhibition of cancer growth. 

PMID- 24866116
TI  - Extrinsic and intrinsic control by EKLF (KLF1) within a specialized erythroid
      niche.
AB  - The erythroblastic island provides an important nutritional and survival support
      niche for efficient erythropoietic differentiation. Island integrity is reliant
      on adhesive interactions between erythroid and macrophage cells. We show that
      erythroblastic islands can be formed from single progenitor cells present in
      differentiating embryoid bodies, and that these correspond to erythro-myeloid
      progenitors (EMPs) that first appear in the yolk sac of the early developing
      embryo. Erythroid Kruppel-like factor (EKLF; KLF1), a crucial zinc finger
      transcription factor, is expressed in the EMPs, and plays an extrinsic role in
      erythroid maturation by being expressed in the supportive macrophage of the
      erythroblastic island and regulating relevant genes important for island
      integrity within these cells. Together with its well-established intrinsic
      contributions to erythropoiesis, EKLF thus plays a coordinating role between two
      different cell types whose interaction provides the optimal environment to
      generate a mature red blood cell. 

PMID- 24866124
TI  - Dissecting the subcellular compartmentation of proteins and metabolites in
      arabidopsis leaves using non-aqueous fractionation.
AB  - Non-aqueous fractionation is a technique for the enrichment of different
      subcellular compartments derived from lyophilized material. It was developed to
      study the subcellular distribution of metabolites. Here we analyzed the
      distribution of about 1,000 proteins and 70 metabolites, including 22
      phosphorylated intermediates in wild-type Arabidopsis rosette leaves, using non
      aqueous gradients divided into 12 fractions. Good separation of plastidial,
      cytosolic, and vacuolar metabolites and proteins was achieved, but cytosolic,
      mitochondrial, and peroxisomal proteins clustered together. There was
      considerable heterogeneity in the fractional distribution of transcription
      factors, ribosomal proteins, and subunits of the vacuolar-ATPase, indicating
      diverse compartmental location. Within the plastid, sub-organellar separation of
      thylakoids and stromal proteins was observed. Metabolites from the Calvin-Benson
      cycle, photorespiration, starch and sucrose synthesis, glycolysis, and the
      tricarboxylic acid cycle grouped with their associated proteins of the respective
      compartment. Non-aqueous fractionation thus proved to be a powerful method for
      the study of the organellar, and in some cases sub-organellar, distribution of
      proteins and their association with metabolites. It remains the technique of
      choice for the assignment of subcellular location to metabolites in intact plant
      tissues, and thus the technique of choice for doing combined metabolite-protein
      analysis on a single tissue sample. 

PMID- 24866125
TI  - Rapid mapping of interactions between Human SNX-BAR proteins measured in vitro by
      AlphaScreen and single-molecule spectroscopy.
AB  - Protein dimerization and oligomerization is commonly used by nature to increase
      the structural and functional complexity of proteins. Regulated protein assembly
      is essential to transfer information in signaling, transcriptional, and membrane
      trafficking events. Here we show that a combination of cell-free protein
      expression, a proximity based interaction assay (AlphaScreen), and single
      molecule fluorescence allow rapid mapping of homo- and hetero-oligomerization of
      proteins. We have applied this approach to the family of BAR domain-containing
      sorting nexin (SNX-BAR) proteins, which are essential regulators of membrane
      trafficking and remodeling in all eukaryotes. Dimerization of BAR domains is
      essential for creating a concave structure capable of sensing and inducing
      membrane curvature. We have systematically mapped 144 pairwise interactions
      between the human SNX-BAR proteins and generated an interaction matrix of
      preferred dimerization partners for each family member. We find that while nine
      SNX-BAR proteins are able to form homo-dimers, several including the retromer
      associated SNX1, SNX2, and SNX5 require heteromeric interactions for
      dimerization. SNX2, SNX4, SNX6, and SNX8 show a promiscuous ability to bind other
      SNX-BAR proteins and we also observe a novel interaction with the SNX3 protein
      which lacks the BAR domain structure. 

PMID- 24866129
TI  - The Saccharomyces cerevisiae quinone oxidoreductase Lot6p: stability, inhibition
      and cooperativity.
AB  - Lot6p (EC 1.5.1.39; Ylr011wp) is the sole quinone oxidoreductase in the budding
      yeast, Saccharomyces cerevisiae. Using hexahistidine tagged, recombinant Lot6p,
      we determined the steady-state enzyme kinetic parameters with both NADH and NADPH
      as electron donors; no cooperativity was observed with these substrates. The NQO1
      inhibitor curcumin, the NQO2 inhibitor resveratrol, the bacterial nitroreductase
      inhibitor nicotinamide and the phosphate mimic vanadate all stabilise the enzyme
      towards thermal denaturation as judged by differential scanning fluorimetry. All
      except vanadate have no observable effect on the chemical cross-linking of the
      two subunits of the Lot6p dimer. These compounds all inhibit Lot6p's
      oxidoreductase activity, and all except nicotinamide exhibit negative
      cooperativity. Molecular modelling suggests that curcumin, resveratrol and
      nicotinamide all bind over the isoalloxazine ring of the FMN cofactor in Lot6p.
      Resveratrol was predicted to contact an alpha-helix that links the two active
      sites. Mutation of Gly-142 (which forms part of this helix) to serine does not
      greatly affect the thermal stability of the enzyme. However, this variant shows
      less cooperativity towards resveratrol than the wild type. This suggests a
      plausible hypothesis for the transmission of information between the subunits
      and, thus, the molecular mechanism of negative cooperativity in Lot6p. 

PMID- 24866127
TI  - Exceptional evolutionary divergence of human muscle and brain metabolomes
      parallels human cognitive and physical uniqueness.
AB  - Metabolite concentrations reflect the physiological states of tissues and cells.
      However, the role of metabolic changes in species evolution is currently unknown.
      Here, we present a study of metabolome evolution conducted in three brain regions
      and two non-neural tissues from humans, chimpanzees, macaque monkeys, and mice
      based on over 10,000 hydrophilic compounds. While chimpanzee, macaque, and mouse
      metabolomes diverge following the genetic distances among species, we detect
      remarkable acceleration of metabolome evolution in human prefrontal cortex and
      skeletal muscle affecting neural and energy metabolism pathways. These metabolic
      changes could not be attributed to environmental conditions and were confirmed
      against the expression of their corresponding enzymes. We further conducted
      muscle strength tests in humans, chimpanzees, and macaques. The results suggest
      that, while humans are characterized by superior cognition, their muscular
      performance might be markedly inferior to that of chimpanzees and macaque
      monkeys. 

PMID- 24866126
TI  - The in vivo therapeutic efficacy of the oncolytic adenovirus Delta24-RGD is
      mediated by tumor-specific immunity.
AB  - The oncolytic adenovirus Delta24-RGD represents a new promising therapeutic agent
      for patients with a malignant glioma and is currently under investigation in
      clinical phase I/II trials. Earlier preclinical studies showed that Delta24-RGD
      is able to effectively lyse tumor cells, yielding promising results in various
      immune-deficient glioma models. However, the role of the immune response in
      oncolytic adenovirus therapy for glioma has never been explored. To this end, we
      assessed Delta24-RGD treatment in an immune-competent orthotopic mouse model for
      glioma and evaluated immune responses against tumor and virus. Delta24-RGD
      treatment led to long-term survival in 50% of mice and this effect was completely
      lost upon administration of the immunosuppressive agent dexamethasone. Delta24
      RGD enhanced intra-tumoral infiltration of F4/80+ macrophages, CD4+ and CD8+ T
      cells, and increased the local production of pro-inflammatory cytokines and
      chemokines. In treated mice, T cell responses were directed to the virus as well
      as to the tumor cells, which was reflected in the presence of protective
      immunological memory in mice that underwent tumor rechallenge. Together, these
      data provide evidence that the immune system plays a vital role in the
      therapeutic efficacy of oncolytic adenovirus therapy of glioma, and may provide
      angles to future improvements on Delta24-RGD therapy. 

PMID- 24866130
TI  - Posterior meniscus root tears: associated pathologies to assist as diagnostic
      tools.
AB  - PURPOSE: The purpose of this study was to investigate associated pathologies
      identified at arthroscopy in patients with meniscus root tears. METHODS: This
      study was Institutional Review Board approved. All patients who underwent
      arthroscopic knee surgery where a complete meniscus root tear was identified were
      included in this study. Concurrent ligament tears and articular cartilage changes
      >=Outerbridge grade 2 were recorded and stored in a data registry. RESULTS: Fifty
      patients (28 males, 22 females) [mean age = 36.5 years (range 17.1-68.1 years)]
      who were diagnosed with a medial or lateral meniscus root tear at arthroscopy
      were included in this study out of 673 arthroscopic surgeries (prevalence 7.4 %).
      Twenty-three (46 %) patients had a medial meniscus root tear, 26 (52 %) patients
      had a lateral meniscus root tear and one (2 %) patient had both. Thirty-four per
      cent of patients (n = 17) underwent partial meniscectomy, while 60 % (n = 31)
      underwent suture repair. During arthroscopy, 60 % (n = 30) of patients were
      diagnosed with an anterior cruciate ligament (ACL) tear. Patients with lateral
      meniscus root tears were 10.3 times (95 % CI 2.6-42.5) more likely to have ACL
      tears than patients with medial meniscus root tears (p = 0.012). Patients who had
      medial meniscus root tears were 5.8 times (95 % CI 1.6-20.5) more likely to have
      chondral defects than patients who had lateral meniscus root tears (p = 0.044).
      CONCLUSION: In this study, patients' preoperative functional scores and activity
      levels were low. Patients with lateral meniscal root tears were more likely to
      have an ACL tear. Patients with medial meniscal root tears were more likely to
      have an knee articular cartilage defect with an Outerbridge grade 2 or higher
      chondral defect. This study confirms the importance of comprehensive assessment
      of concurrent injuries to properly diagnose meniscus root tears. LEVEL OF
      EVIDENCE: IV.

PMID- 24866131
TI  - Serelaxin is a more efficacious antifibrotic than enalapril in an experimental
      model of heart disease.
AB  - Relaxin is a naturally occurring peptide hormone that mediates systemic
      hemodynamic and renal adaptive changes during pregnancy and abrogates aberrant
      scar tissue formation (fibrosis) in diverse pathogeneses. However, its efficacy
      relative to renin-angiotensin system blockade, the most effective antifibrotic
      strategy currently available, is not known. We compared the individual versus
      combined antifibrotic effects of serelaxin (a recombinant form of human gene-2
      relaxin) and the angiotensin-converting enzyme inhibitor enalapril, in
      preventative (started before injury) and therapeutic (treatment of established
      fibrosis) strategies, in a mouse model of isoprenaline-induced cardiac injury (at
      17 days). Changes in systolic blood pressure, organ hypertrophy, and tissue
      remodeling/fibrosis were assessed. Pretreatment with serelaxin (0.5 mg/kg per day
      via subcutaneous administration) alone reduced cardiac fibrosis to a greater
      extent than enalapril (200 mg/L via drinking water; equivalent to 48 mg/kg per
      day) alone (P<0.05 versus enalapril alone). Additionally, the combined effects of
      serelaxin and enalapril reduced cardiac fibrosis by at least 2-fold compared with
      enalapril alone, when administered preventatively or therapeutically; by
      suppressing transforming growth factor-beta1 expression and phosphorylation of
      Smad2 (an intracellular regulator of transforming growth factor-beta1 activity;
      both P<0.05 versus enalapril alone) to a greater extent. The effects of serelaxin
      were independent of blood pressure, while enalapril lowered systolic blood
      pressure in the model studied. These findings suggest that serelaxin alone and in
      combination with an angiotensin-converting enzyme inhibitor more effectively
      ameliorates fibrosis than angiotensin-converting enzyme inhibition alone in the
      diseased heart, in a clinically relevant experimental scenario.

PMID- 24866133
TI  - One step forward for serelaxin as a promising therapy in cardiac fibrosis.

PMID- 24866132
TI  - Genetic spectrum and clinical correlates of somatic mutations in aldosterone
      producing adenoma.
AB  - Primary aldosteronism is the most common form of secondary hypertension. Somatic
      mutations in KCNJ5, ATP1A1, ATP2B3, and CACNA1D have been described in
      aldosterone-producing adenomas (APAs). Our aim was to investigate the prevalence
      of somatic mutations in these genes in unselected patients with APA (n=474),
      collected through the European Network for the Study of Adrenal Tumors.
      Correlations with clinical and biochemical parameters were first analyzed in a
      subset of 199 patients from a single center and then replicated in 2 additional
      centers. Somatic heterozygous KCNJ5 mutations were present in 38% (180/474) of
      APAs, whereas ATP1A1 mutations were found in 5.3% (25/474) and ATP2B3 mutations
      in 1.7% (8/474) of APAs. Previously reported somatic CACNA1D mutations as well as
      10 novel CACNA1D mutations were identified in 44 of 474 (9.3%) APAs. There was no
      difference in the cellular composition of APAs or in CYP11B2, CYP11B1, KCNJ5,
      CACNA1D, or ATP1A1 gene expression in APAs across genotypes. Patients with KCNJ5
      mutations were more frequently female, diagnosed younger, and with higher minimal
      plasma potassium concentrations compared with CACNA1D mutation carriers or
      noncarriers. CACNA1D mutations were associated with smaller adenomas. These
      associations were largely dependent on the population structure of the different
      centers. In conclusion, recurrent somatic mutations were identified in 54% of
      APAs. Young women with APAs are more likely to be KCNJ5 mutation carriers;
      identification of specific characteristics or surrogate biomarkers of mutation
      status may lead to targeted treatment options. 

PMID- 24866134
TI  - Inhibition of ERK1/2 phosphorylation: a new strategy to stimulate elastogenesis
      in the aorta.
AB  - Haploinsufficiency of elastin leads, in more than half of patients with Williams
      Beuren syndrome, to development of supravalvular aortic stenosis and
      hypertension. Determining mechanisms implicated in elastin synthesis would be of
      interest to find new elastogenic molecules to treat such a pathology. Here, we
      analyzed the signaling pathway linking intracellular calcium concentration to
      elastin regulation to find new molecules able to increase elastin synthesis.
      Their elastogenic ability was then investigated, in vitro and in vivo, using
      inhibitors of the highlighted pathway. The Brown Norway rat strain was used here
      as an arterial elastin-deficient model. Our data indicated that A23187, a calcium
      ionophore, decreases elastin expression in cultured vascular smooth muscle cells,
      both transcriptionally and post-transcriptionally. Addition of A23187 induced
      transient activation of extracellular signal-regulated kinases 1/2, leading to an
      upregulation of activator protein-1 transcription factors, which correlated with
      the inhibition of elastin gene transcription. Pretreatment with U0126, an
      inhibitor of extracellular signal-regulated kinases 1/2 phosphorylation,
      abolished the inhibition of elastin gene transcription by A23187. In vitro, U0126
      increased elastin synthesis and in vivo, 24 hours after an intravenous
      administration, elastin gene transcription and elastin mRNA levels were increased
      in the rat aorta. A chronic treatment, diffusing U0126 for 10 weeks, increased
      aortic elastin content without changing cell number and collagen content. In
      conclusion, calcium ionophore represses elastin gene transcription via activation
      of extracellular signal-regulated kinases 1/2 pathway and activator protein-1
      transcription factors. Moreover, we provide strong evidence that inhibition of
      extracellular signal-regulated kinases 1/2 increases elastin synthesis and could
      thus be suitable for treating vascular pathologies characterized by diminished
      arterial elastin content. 

PMID- 24866135
TI  - Sodium shows no mercy on the nanomechanics of endothelial cells.

PMID- 24866136
TI  - In search of the T cell involved in hypertension and target organ damage.

PMID- 24866138
TI  - Improving the prediction of hypertensive target organ damage using novel markers:
      lessons from retinal vascular imaging research.

PMID- 24866137
TI  - Gestational hypoxia increases reactive oxygen species and inhibits steroid
      hormone-mediated upregulation of Ca(2+)-activated K(+) channel function in
      uterine arteries.
AB  - Gestational hypoxia inhibits steroid hormone-induced upregulation of Ca(2+)
      activated K(+) (KCa) channel activities in uterine arteries. We tested the
      hypothesis that increased reactive oxygen species play an important role in
      hypoxia-mediated inhibition of KCa channel activities. Uterine arteries were
      isolated from nonpregnant (nonpregnant uterine artery) and near-term (~142-145
      day) pregnant (pregnant uterine artery) sheep maintained at either sea level or
      high altitude (3820 m, Pao2: 60 mm Hg) for 110 days. In pregnant uterine
      arteries, hypoxia significantly decreased large conductance channel opener NS1619
      and small conductance channel opener NS309-induced relaxations, which were
      partially restored by reactive oxygen species inhibitor N-acetylcysteine (NAC).
      NAC significantly increased large conductance KCa but not small conductance KCa
      current densities in uterine arterial smooth muscle cells in pregnant animals
      acclimatized to high altitude. The NAC-sensitive component of small conductance
      KCa-induced relaxations was diminished in endothelium-denuded arteries. In
      nonpregnant uterine arteries, NS1619- and NS309-induced relaxations were
      diminished compared with those in pregnant uterine arteries. Treatment of
      nonpregnant uterine arteries with 17beta-estradiol and progesterone for 48 hours
      increased small conductance KCa type 3 protein abundance and NS1619- and NS309
      induced relaxations, which were inhibited by hypoxia. This hypoxia-mediated
      inhibition was reversed by NAC. Consistently, steroid hormone treatment had no
      significant effects on large conductance KCa current density in nonpregnant
      uterine arteries of hypoxic animals in the absence of NAC but significantly
      increased it in the presence of NAC. These results suggest an important role of
      hypoxia-mediated reactive oxygen species in negatively regulating steroid hormone
      mediated upregulation of KCa channel activity and adaptation of uterine vascular
      reactivity in pregnancy, which may contribute to the increased incidence of
      preeclampsia and fetal intrauterine growth restriction associated with
      gestational hypoxia. 

PMID- 24866139
TI  - gammadeltaT Cell-derived interleukin-17A via an interleukin-1beta-dependent
      mechanism mediates cardiac injury and fibrosis in hypertension.
AB  - Inflammation is implicated in the initiation of hypertension and end-organ
      injury. Interleukin-17A (IL-17A) is a key pathogenic factor in a variety of
      inflammatory diseases and hypertension. However, the mechanisms underlying IL-17A
      production, and its role in mediating inflammation and early cardiovascular
      injury in hypertensive heart, remain unknown. Angiotensin II (Ang II) infusion
      increased cardiac IL-17A mRNA expression and IL-17A+CD3+ cell infiltration in a
      time-dependent manner. IL-17A in the hypertensive heart was derived mostly from
      infiltrating gammadeltaT cells rather than from CD4 T cells. Genetic knockdown of
      gammadeltaT cells or specific anti-gammadeltaT antibody abolished IL-17A
      production in Ang II-infused heart. Moreover, monocyte-secreted IL-1beta, not
      cardiac fibroblast-secreted IL-6 or transforming growth factor-beta, was required
      for IL-17A production from gammadeltaT cell. IL-17A accelerated differentiation
      of myofibroblast through promoting IL-6 production from cardiac fibroblast.
      Finally, inflammatory cell infiltration, proinflammatory or profibrotic cytokine
      expression, and fibrotic lesion induced by Ang II were attenuated in IL-17A
      deficient mice. Moreover, the deletion of gammadeltaT cell was protected from Ang
      II-induced cardiac injury. Thus, a triangular positive feedback loop exists among
      monocytic-secreted IL-1beta, gammadeltaT-cell-derived IL-17A, and cardiac
      fibroblast-produced IL-6, which triggers the cardiac injury in hypertension.

PMID- 24866140
TI  - Long-term sympathoinhibitory effects of surgically induced weight loss in severe
      obese patients.
AB  - Weight loss improves insulin sensitivity and exerts sympathomodulatory effects.
      No data, however, are available on the effects of the weight loss induced by
      vertical sleeve gastrectomy on sympathetic neural drive, insulin sensitivity, and
      their reciprocal cross talks. In 10 severe obese hypertensives (age, 54.0+/-2.3
      years [mean+/-SEM]), we measured sphygmomanometric blood pressure, heart rate,
      body mass index, homeostatic model assessment index, plasma leptin, muscle
      sympathetic nerve traffic (microneurography), and baroreflex sensitivity
      (vasoactive drug technique). Measurements were performed 2 to 3 days before
      surgery and repeated 6 and 12 months after the procedure. Ten matched
      hypertensive obeses not undergoing gastrectomy served as controls. Six months
      after bariatric surgery, a significant (P<0.05) reduction in body mass index (
      9.1+/-1.4 kg/m(2)), sphygmomanometric systolic blood pressure (-10.2+/-4.5 mm
      Hg), heart rate (-11.0+/-2.4 bpm), homeostatic model assessment index (-3-3+/-1.3
      AU), plasma leptin (-53.6+/-8.8 MUg/L), and muscle sympathetic nerve traffic (
      15.0+/-3.4 bursts/100 heart beats) was observed. The weight loss, the plasma
      leptin reduction, and the sympathetic inhibition were maintained after 12 months,
      whereas homeostatic model assessment index showed a tendency to return toward
      presurgery values. A significant improvement in baroreflex control of sympathetic
      nerve traffic was observed both 6 (+32.1%; P<0.05) and 12 months (+60.7%; P<0.01)
      after gastrectomy. No significant changes in the above-mentioned variables were
      detected in the control group. These data provide evidence that massive weight
      loss induced by sleeve gastrectomy triggers profound sympathoinhibitory effects,
      associated with a stable and significant reduction in plasma leptin levels,
      whereas the improvement in insulin sensitivity was attenuated with time and
      unrelated to the sympathoinhibition. 

PMID- 24866141
TI  - Sympathetic inhibition after bariatric surgery.

PMID- 24866142
TI  - Forward and backward wave morphology and central pressure augmentation in men and
      women in the Framingham Heart Study.
AB  - Central pressure augmentation is associated with greater backward wave amplitude
      and shorter transit time and is higher in women for reasons only partially
      elucidated. Augmentation also is affected by left ventricular function and shapes
      of the forward and backward waves. The goal of this study was to examine the
      relative contributions of forward and backward wave morphology to central
      pressure augmentation in men and women. From noninvasive measurements of central
      pressure and flow in 7437 participants (4036 women) aged from 19 to 90 years
      (mean age, 51 years), we calculated several variables: augmentation index,
      backward wave arrival time, reflection factor, forward wave amplitude, forward
      wave peak width, and slope of the backward wave upstroke. Linear regression
      models for augmentation index, adjusted for height and heart rate, demonstrated
      nonlinear relations with age (age: B=4.6+/-0.1%; P<0.001; age2: B=-4.2+/-0.1%;
      P<0.001) and higher augmentation in women (B=4.5+/-0.4%; P<0.001; model R2=0.35).
      Addition of reflection factor and backward wave arrival time improved model fit
      (R2=0.62) and reduced the age coefficients: age (B=2.3+/-0.1%; P<0.001) and age2
      (B=-2.2+/-0.1%; P<0.001). Addition of width of forward wave peak, slope of
      backward wave upstroke, and forward wave amplitude further improved model fit
      (R2=0.75) and attenuated the sex coefficient (B=1.9+/-0.2%; P<0.001). Thus, shape
      and amplitude of the forward wave may be important correlates of augmentation
      index, and part of the sex difference in augmentation index may be explained by
      forward and backward wave morphology.

PMID- 24866143
TI  - Endothelial sodium channels trigger endothelial salt sensitivity with aging.
AB  - The epithelial sodium channel is also expressed in vascular endothelium
      (endothelial sodium channel [EnNaC]). Depending on ambient sodium concentration,
      EnNaC is associated with mechanical stiffening of the endothelial cell cortex,
      leading to endothelial dysfunction. Because the incidence of both salt
      sensitivity and endothelial dysfunction increases with age, we investigated the
      abundance of EnNaC in aging mice. To assess EnNaC functionality and endothelial
      salt sensitivity, stiffness was measured while ambient sodium was varied. Aortae
      of young (3 months) and old (15 months) C57BL/6J wild-type mice were kept ex vivo
      on a physiological concentration of aldosterone (0.45 nmol/L). Spironolactone (10
      nmol/L) and amiloride (1 MUmol/L) were applied for aldosterone antagonism and
      EnNaC blockage, respectively. EnNaC at the endothelial cell surface was
      quantified by immunofluorescence staining. Cortical stiffness was monitored by
      atomic force microscopy when ambient sodium was raised from 135 to 150 mmol/L. In
      ex vivo aortae of older mice, endothelial cells had significantly higher EnNaC
      numbers than those of younger mice (+23%). In parallel, cortical stiffness was
      found increased (+8.5%). Acute application of high sodium led to an immediate
      rise in stiffness in both groups but was pronounced in endothelium of older mice
      (+18% versus +26%). Spironolactone and amiloride lowered EnNaC abundance and
      prevented endothelial stiffening under all conditions. We conclude that EnNaC
      mediates endothelial salt sensitivity in the aging process. This mechanism might
      contribute to the development of age-related cardiovascular disease and suggests
      the usage of spironolactone and amiloride specifically in the elderly. 

PMID- 24866144
TI  - L-Citrulline, but not L-arginine, prevents diabetes mellitus-induced glomerular
      hyperfiltration and proteinuria in rat.
AB  - Diabetes mellitus-induced oxidative stress causes increased renal oxygen
      consumption and intrarenal tissue hypoxia. Nitric oxide is an important
      determinant of renal oxygen consumption and electrolyte transport efficiency. The
      present study investigates whether l-arginine or l-citrulline to promote nitric
      oxide production prevents the diabetes mellitus-induced kidney dysfunction.
      Glomerular filtration rate, renal blood flow, in vivo oxygen consumption, tissue
      oxygen tension, and proteinuria were investigated in control and streptozotocin
      diabetic rats with and without chronic l-arginine or l-citrulline treatment for 3
      weeks. Untreated and l-arginine-treated diabetic rats displayed increased
      glomerular filtration rate (2600+/-162 versus 1599+/-127 and 2290+/-171 versus
      1739+/-138 MUL/min per kidney), whereas l-citrulline prevented the increase
      (1227+/-126 versus 1375+/-88 MUL/min per kidney). Filtration fraction was
      increased in untreated diabetic rats because of the increase in glomerular
      filtration rate but not in l-arginine- or l-citrulline-treated diabetic rats.
      Urinary protein excretion was increased in untreated and l-arginine-treated
      diabetic rats (142+/-25 versus 75+/-7 and 128+/-7 versus 89+/-7 MUg/min per
      kidney) but not in diabetic rats administered l-citrulline (67+/-7 versus 61+/-5
      MUg/min per kidney). The diabetes mellitus-induced tissue hypoxia, because of
      elevated oxygen consumption, was unaltered by any of the treatments. l-citrulline
      administered to diabetic rats increases plasma l-arginine concentration, which
      prevents the diabetes mellitus-induced glomerular hyperfiltration, filtration
      fraction, and proteinuria, possibly by a vascular effect.

PMID- 24866145
TI  - Maternal parity, fetal and childhood growth, and cardiometabolic risk factors.
AB  - We examined the associations of maternal parity with fetal and childhood growth
      characteristics and childhood cardiometabolic risk factors in a population-based
      prospective cohort study among 9031 mothers and their children. Fetal and
      childhood growth were repeatedly measured. We measured childhood anthropometrics,
      body fat distribution, left ventricular mass, blood pressure, blood lipids, and
      insulin levels at the age of 6 years. Compared with nulliparous mothers,
      multiparous mothers had children with higher third trimester fetal head
      circumference, length and weight growth, and lower risks of preterm birth and
      small-size-for-gestational-age at birth but a higher risk of large-size-for
      gestational-age at birth (P<0.05). Children from multiparous mothers had lower
      rates of accelerated infant growth and lower levels of childhood body mass index,
      total fat mass percentage, and total and low-density lipoprotein cholesterol than
      children of nulliparous mothers (P<0.05). They also had a lower risk of childhood
      overweight (odds ratio, 0.75 [95% confidence interval, 0.63-0.88]). The risk of
      childhood clustering of cardiometabolic risk factors was not statistically
      significantly different (odds ratio, 0.82; 95% confidence interval, 0.64-1.05).
      Among children from multiparous mothers only, we observed consistent trends
      toward a lower risk of childhood overweight and lower cholesterol levels with
      increasing parity (P<0.05). In conclusion, offspring from nulliparous mothers
      have lower fetal but higher infant growth rates and higher risks of childhood
      overweight and adverse metabolic profile. Maternal nulliparity may have
      persistent cardiometabolic consequences for the offspring.

PMID- 24866146
TI  - Microcirculatory marker for the prediction of renal end points: a prospective
      cohort study in patients with chronic kidney disease stage 2 to 4.
AB  - Retinal arteriolar narrowing reflects aging, hypertension, chronic kidney disease
      (CKD), and other vascular processes. We examined the predictive value of retinal
      arteriolar narrowing alone and in combination with albuminuria on renal disease
      progression in CKD. A white CKD stage 2 to 4 cohort of 164 men and women (60.8+/
      13.8 years) underwent retinal photography and determination of albuminuria. The
      calibers of all retinal arterioles were measured after digital conversion of the
      photographs. Cases of incident renal end points defined as 50% renal function
      loss and start of renal replacement therapy were identified and validated by case
      record reviews. Over an average period of 1410 (range, 106-1606) days, 25
      patients with CKD had incident renal end points. Kaplan-Meier analysis revealed
      that patients with CKD within the tertile of narrowest arterioles had more renal
      end points (log-rank P<0.001). Cox regression analysis confirmed this before
      (beta=1.183+/-0.411) and after adjusting for age and baseline renal function
      (beta=1.204+/-0.416). With respect to renal end points, a significant interaction
      was present between narrow arterioles and albuminuria. The relative risk for
      renal end points of narrow arterioles was 3.7 (1.7-8.4), of albuminuria was 5.4
      (2.5-12.0), and of combined narrow arterioles and albuminuria was 16.2 (4.6
      57.2). Hence retinal arteriolar narrowing is related to incident renal end
      points. Narrow arterioles and albuminuria reveal a synergistic predictive value.
      The findings support a leading role of the microvasculature in the pathogenesis
      of renal disease progression. They also suggest that retinal photography in
      combination with albuminuria determination may be useful for risk stratification
      with respect to renal disease progression in patients with CKD stage 2 to 4. 

PMID- 24866148
TI  - Selective monooxidation of light alkanes using chloride and iodate.
AB  - We describe an efficient system for the direct partial oxidation of methane,
      ethane, and propane using iodate salts with catalytic amounts of chloride in
      protic solvents. In HTFA (TFA = trifluoroacetate), >20% methane conversion with
      >85% selectivity for MeTFA have been achieved. The addition of substoichiometric
      amounts of chloride is essential, and for methane the conversion increases from
      <1% in the absence of chloride to >20%. The reaction also proceeds in aqueous
      HTFA as well as acetic acid to afford methyl acetate. (13)C labeling experiments
      showed that less than 2% of methane is overoxidized to (13)CO2 at 15% conversion
      of (13)CH4. The system is selective for higher alkanes: 30% ethane conversion
      with 98% selectivity for EtTFA and 19% propane conversion that is selective for
      mixtures of the mono- and difunctionalized TFA esters. Studies of methane
      conversion using a series of iodine-based reagents [I2, ICl, ICl3, I(TFA)3, I2O4,
      I2O5, (IO2)2S2O7, (IO)2SO4] indicated that the chloride enhancement is not
      limited to iodate. 

PMID- 24866147
TI  - Prostaglandin E-prostanoid4 receptor mediates angiotensin II-induced (pro)renin
      receptor expression in the rat renal medulla.
AB  - Angiotensin II (Ang II) stimulates (pro)renin receptor (PRR) expression in the
      renal collecting duct, triggering the local renin response in the distal nephron.
      Our recent study provided evidence for involvement of cyclooxygenase-2
      prostaglandin E2 pathway in Ang II-dependent stimulation of PRR expression in the
      collecting duct. Here, we tested the role of E-prostanoid (EP) subtypes acting
      downstream of cyclooxygenase-2 in this phenomenon. In primary rat inner medullary
      collecting duct cells, Ang II treatment for 12 hours induced a 1.8-fold increase
      in the full-length PRR protein expression. To assess the contribution of EP
      receptor, the cell was pretreated with specific EP receptor antagonists: SC-51382
      (for EP1), L-798106 (for EP3), L-161982 (for EP4), and ONO-AE3-208 (ONO, a
      structurally distinct EP4 antagonist). The upregulation of PRR expression by Ang
      II was consistently abolished by L-161982 and ONO and partially suppressed by SC
      51382 but was unaffected by L-798106. The PRR expression was also significantly
      elevated by the EP4 agonist CAY10598 in the absence of Ang II. Sprague-Dawley
      rats were subsequently infused for 1 or 2 weeks with vehicle, Ang II alone, or in
      combination with ONO. Ang II infusion induced parallel increases in renal
      medullary PRR protein and renal medullary and urinary renin activity and total
      renin content, all of which were blunted by ONO. Both tail cuff plethysmography
      and telemetry demonstrated attenuation of Ang II hypertension by ONO. Overall,
      these results have established a crucial role of the EP4 receptor in mediating
      the upregulation of renal medullary PRR expression and renin activity during Ang
      II hypertension. 

PMID- 24866149
TI  - The reference transcriptome of the adult female biting midge (Culicoides
      sonorensis) and differential gene expression profiling during teneral, blood, and
      sucrose feeding conditions.
AB  - Unlike other important vectors such as mosquitoes and sandflies, genetic and
      genomic tools for Culicoides biting midges are lacking, despite the fact that
      they vector a large number of arboviruses and other pathogens impacting humans
      and domestic animals world-wide. In North America, female Culicoides sonorensis
      midges are important vectors of bluetongue virus (BTV) and epizootic hemorrhagic
      disease virus (EHDV), orbiviruses that cause significant disease in livestock and
      wildlife. Libraries of tissue-specific transcripts expressed in response to
      feeding and oral orbivirus challenge in C. sonorensis have previously been
      reported, but extensive genome-wide expression profiling in the midge has not.
      Here, we successfully used deep sequencing technologies to construct the first
      adult female C. sonorensis reference transcriptome, and utilized genome-wide
      expression profiling to elucidate the genetic response to blood and sucrose
      feeding over time. The adult female midge unigene consists of 19,041 genes, of
      which less than 7% are differentially expressed during the course of a sucrose
      meal, while up to 52% of the genes respond significantly in blood-fed midges,
      indicating hematophagy induces complex physiological processes. Many genes that
      were differentially expressed during blood feeding were associated with digestion
      (e.g. proteases, lipases), hematophagy (e.g., salivary proteins), and
      vitellogenesis, revealing many major metabolic and biological factors underlying
      these critical processes. Additionally, key genes in the vitellogenesis pathway
      were identified, which provides the first glimpse into the molecular basis of
      anautogeny for C. sonorensis. This is the first extensive transcriptome for this
      genus, which will serve as a framework for future expression studies, RNAi, and
      provide a rich dataset contributing to the ultimate goal of informing a reference
      genome assembly and annotation. Moreover, this study will serve as a foundation
      for subsequent studies of genome-wide expression analyses during early orbivirus
      infection and dissecting the molecular mechanisms behind vector competence in
      midges. 

PMID- 24866152
TI  - Testing fluorescence lifetime standards using two-photon excitation and time
      domain instrumentation: rhodamine B, coumarin 6 and lucifer yellow.
AB  - Having good information about fluorescence lifetime standards is essential for
      anyone performing lifetime experiments. Using lifetime standards in fluorescence
      spectroscopy is often regarded as a straightforward process, however, many
      earlier reports are limited in terms of lifetime concentration dependency,
      solvents and other technical aspects. We have investigated the suitability of the
      fluorescent dyes rhodamine B, coumarin 6, and lucifer yellow as lifetime
      standards, especially to be used with two-photon excitation measurements in the
      time-domain. We measured absorption and emission spectra for the fluorophores to
      determine which wavelengths we should use for the excitation and an appropriate
      detector range. We also measured lifetimes for different concentrations, ranging
      from 10(-2)- 10(-6) M, in both water, ethanol and methanol solutions. We observed
      that rhodamine B lifetimes depend strongly on concentration. Coumarin 6 provided
      the most stable lifetimes, with a negligible dependency on concentration and
      solvent. Lucifer yellow lifetimes were also found to depend little with
      concentration. Finally, we found that a mix of two fluorophores (rhodamine
      B/coumarin 6, rhodamine B/lucifer yellow, and coumarin 6/lucifer yellow) all
      yielded very similar lifetimes from a double-exponential decay as the separate
      lifetimes measured from a single-exponential decay. All lifetime measurements
      were made using two-photon excitation and obtaining lifetime data in the time
      domain using time-correlated single-photon counting. 

PMID- 24866151
TI  - Vulnerabilities of PTEN-TP53-deficient prostate cancers to compound PARP-PI3K
      inhibition.
AB  - Prostate cancer is the most prevalent cancer in males, and treatment options are
      limited for advanced forms of the disease. Loss of the PTEN and TP53 tumor
      suppressor genes is commonly observed in prostate cancer, whereas their compound
      loss is often observed in advanced prostate cancer. Here, we show that PARP
      inhibition triggers a p53-dependent cellular senescence in a PTEN-deficient
      setting in the prostate. Surprisingly, we also find that PARP-induced cellular
      senescence is morphed into an apoptotic response upon compound loss of PTEN and
      p53. We further show that superactivation of the prosurvival PI3K-AKT signaling
      pathway limits the efficacy of a PARP single-agent treatment, and that PARP and
      PI3K inhibitors effectively synergize to suppress tumorigenesis in human prostate
      cancer cell lines and in a Pten/Trp53-deficient mouse model of advanced prostate
      cancer. Our findings, therefore, identify a combinatorial treatment with PARP and
      PI3K inhibitors as an effective option for PTEN-deficient prostate cancer.
      SIGNIFICANCE: The paucity of therapeutic options in advanced prostate cancer
      displays an urgent need for the preclinical assessment of novel therapeutic
      strategies. We identified differential therapeutic vulnerabilities that emerge
      upon the loss of both PTEN and p53, and observed that combined inhibition of PARP
      and PI3K provides increased efficacy in hormone-insensitive advanced prostate
      cancer.

PMID- 24866153
TI  - A quinoline derivative as an efficient sensor to detect selectively Al3+ ion.
AB  - A quinoline-based Schiff base 1 has been utilized as a fluorescence chemosensor
      for the selective detection of Al(3+). The receptor 1 exhibited a high
      association constant (3.67 * 10(5) M(-1)) with submicromolar detection limit
      (0.18 ppm) towards Al(3+) in CH3CN solution.

PMID- 24866154
TI  - Spectroscopic and molecular modeling based approaches to study on the binding
      behavior of DNA with a copper (II) complex.
AB  - Blocking the division of tumor cells by small-molecules is currently of great
      interest for the design of new antitumor drugs. The interaction of a new metal
      complex with DNA was investigated through several techniques. Absorption
      spectroscopy and gel electrophoresis studies on the interaction of the Cu-complex
      of (2a-4mpyH)2 [Cu(pyzdc)2 (H2O)2].6 H2O with DNA have shown that this complex
      can bind to CT-DNA with binding constant 3.99 * 10(5) M(-1). The cyclic
      voltammetry (CV) responses of the metal complex in the presence of CT-DNA have
      shown that the metal complex can bind to CT-DNA through partial intercalation
      mode and this is consistent with molecular docking analysis, quenching process
      and thermal denaturation experiments. The cytotoxicity of this complex has been
      evaluated by MTT assay. The results of cell viability assay on DU145 cell line
      revealed that the metal complex had cytotoxic effects.

PMID- 24866156
TI  - Anti-inflammatory effects of rebamipide eyedrop administration on ocular lesions
      in a murine model of primary Sjogren's syndrome.
AB  - BACKGROUND: Topical therapy is effective for dry eye, and its prolonged effects
      should help in maintaining the quality of life of patients with dry eye. We
      previously reported that the oral administration of rebamipide (Reb), a mucosal
      protective agent, had a potent therapeutic effect on autoimmune lesions in a
      murine model of Sjogren's syndrome (SS). However, the effects of topical
      treatment with Reb eyedrops on the ocular lesions in the murine model of SS are
      unknown. METHODS AND FINDING: Reb eyedrops were administered to the murine model
      of SS aged 4-8 weeks four times daily. Inflammatory lesions of the extraorbital
      and intraorbital lacrimal glands and Harderian gland tissues were histologically
      evaluated. The direct effects of Reb on the lacrimal glands were analyzed using
      cultured lacrimal gland cells. Tear secretions of Reb-treated mice were
      significantly increased compared with those of untreated mice. In addition to the
      therapeutic effect of Reb treatment on keratoconjunctivitis, severe inflammatory
      lesions of intraorbital lacrimal gland tissues in this model of SS were resolved.
      The mRNA expression levels of IL-10 and mucin 5Ac in conjunctival tissues from
      Reb-treated mice was significantly increased compared with those of control mice.
      Moreover, lactoferrin production from lacrimal gland cells was restored by Reb
      treatment. CONCLUSION: Topical Reb administration had an anti-inflammatory effect
      on the ocular autoimmune lesions in the murine model of SS and a protective
      effect on the ocular surfaces.

PMID- 24866158
TI  - The empty self and the perils of attachment.
AB  - This article describes clinical work with patients who come to treatment looking
      for help with chronic experiences of emptiness as well as concomitant fears of
      relational impingement. We relate these difficulties to distortions in the
      integration of basic developmental functions, and we suggest a point of view
      including tangible yet unobtrusive interventions that we have found helpful. We
      discuss countertransference issues raised by these patients as well as possible
      etiology. 

PMID- 24866155
TI  - Low level of HIV-1 evolution after transmission from mother to child.
AB  - Mother-to-child HIV-1 transmission pairs represent a good opportunity to study
      the dynamics of CTL escape and reversion after transmission in the light of
      shared and non-shared HLA-alleles. Mothers share half of their HLA alleles with
      their children, while the other half is inherited from the father and is
      generally discordant between mother and child. This implies that HIV-1
      transmitted from mother to child enters a host environment to which it has
      already partially adapted. Here, we studied viral evolution and the dynamics of
      CTL escape mutations and reversion of these mutations after transmission in the
      context of shared and non-shared HLA alleles in viral variants obtained from five
      mother-to-child transmission pairs. Only limited HIV-1 evolution was observed in
      the children after mother-to-child transmission. Viral evolution was mainly
      driven by forward mutations located inside CTL epitopes restricted by HLA alleles
      inherited from the father, which may be indicative of CTL pressure. 

PMID- 24866159
TI  - Disorders as undifferentiated selfobject formations: treatment of a
      multidisordered patient.
AB  - This paper offers a new understanding of disorders as undifferentiated selfobject
      formations. A treatment example of a multipledisordered patient is presented to
      illustrate how disorders diminished as a result of this understanding. This paper
      highlights the developmental importance of the undifferentiated selfobject and
      suggests that early interruptions of this discovery experience that take place
      during the infant's positive moments of freedom and enthusiasm are traumatic. If
      they go beyond the tolerance of the infant, they can be imprinted as unconscious
      core traumatic experiences. They remain as implicit memories that can act as
      warnings of repetitions of the trauma that occurred at the time of freedom and
      enthusiasm in the act of discovering. It can be suggested that the threat of
      repetitions of the traumatic loss is associated with these positive moments of
      discovery. This threat directs the needed self-sustaining undifferentiated
      selfobject discovery experience away from the positive, thereby leaving the
      posttraumatic effects of the loss as the focus of discovery. This focus leads to
      destructive preoccupations and obsessions that are considered disorders such as
      depression, suicidal thinking, self-mutilation, and eating disorders. Once
      patients understand the importance of the undifferentiated selfobject discovery
      need, the delinking of the undifferentiated selfobject from the negative
      preoccupations takes place. As a result, disorders diminish, and patients begin
      to consider positive possibilities for their lives. This paper suggests that
      early interferences in the development of the undifferentiated selfobject lead to
      the formation of disorders. A treatment of a multidisordered patient is presented
      to illustrate how this understanding was central to the diminishing of the
      disorders. 

PMID- 24866160
TI  - Attention deficit disorder or object detachment disorder: a brief psychoanalytic
      case study.
AB  - This paper follows the psychoanalytic treatment of one patient over the course of
      eight sessions. This patient had been diagnosed by two prior therapists as having
      adult attention deficit disorder (ADD). The patient had tried ADD medications and
      ADD behavioral treatments recommended by the therapists. Unsatisfied with the
      results, this individual sought out additional help. She entered analytic
      treatment with the mind-set of knowing what was wrong with her and what type of
      treatment she should receive. Nevertheless, the analyst attempted to remain open
      to finding out the nature of her psychological world and what might be occurring
      on an unconscious level to possibly cause her symptoms. In other words, the
      analyst held the belief that the patient's problems might be more rooted in
      object relational conflicts and at least wanted to offer other alternatives to
      the patient if there were any to be found. Ultimately, the patient was not able
      or willing to consider this possibility. However, in the short duration of the
      treatment, there were various psychological issues that were discovered that may
      have been at the core of this patient's struggles. The paper offers a different
      view of attention deficit disorder, now a very popular diagnosis. The author
      posits that at least some adult attention deficit disorder patients are actually
      suffering from an object detachment process in which they are overwhelmed with a
      variety of unconscious relational conflicts, which create internal and external
      dynamics that in turn create symptoms of inattention, difficulty in focusing,
      disorganization, and scattered thinking. 

PMID- 24866157
TI  - Resveratrol-zinc combination for prostate cancer management.
AB  - Zinc, an essential trace element, plays a critical role in cell signaling, and
      defect(s) in zinc homeostasis may contribute to adverse physiological and
      pathological conditions, including cancer. Zinc is present in healthy prostate at
      a very high concentration, where it is required for important prostatic
      functions. However, zinc levels are significantly diminished in cancerous tissue,
      and intracellular zinc level is inversely correlated with prostate cancer
      progression. During neoplastic transformation, zinc-accumulating, citrate
      producing normal prostate cells are metabolically transformed to citrate
      oxidizing cells that lose the ability to accumulate zinc. Interestingly, zinc has
      been shown to function as chemopreventive agent against prostate cancer, albeit
      at high doses, which may lead to many adverse effects. Therefore, novel means to
      enhance bioaccumulation of sufficient zinc in prostate cells via increasing zinc
      transport could be useful against prostate cancer. On the basis of available
      evidence, we present a possibility that the grape antioxidant resveratrol, when
      given with zinc, may lead to retuning the zinc homeostasis in prostate, thereby
      abolishing or reversing malignancy. If experimentally verified in in vivo
      model(s) of prostate cancer, such as transgenic mouse models, this may lead to
      novel means toward management of prostate cancer and other conditions with
      compromised zinc homeostasis. 

PMID- 24866161
TI  - A Fairbairnian structural analysis of the narcissistic personality disorder.
AB  - Fairbairn's structural theory is based on the developing child's need to
      dissociate actual events between himself or herself and his or her objects that
      are excessively rejecting in order to contine an uninterrupted, pristine
      attachment to them. This eventuates in three selves in relation to three objects:
      One pair is conscious (the central ego which relates to the ideal object), while
      the other two pairs (the antilibidinal ego, which relates to the rejecting
      object, and the libidinal ego, which relates to the exciting object) are mostly
      held in the unconscious. Fairbairn saw the fluid relationship between the two
      split-off pairs of unconscious part selves and the conscious central ego as the
      primary dynamic of the human personality. The author proposes a specific
      variation in Fairbairn's structural theory to account for the development of
      narcissism. Specifically, this disorder is viewed as the result of a
      developmental history in which the child finds himself or herself in an
      exceedingly hostile interpersonal environment that precludes the child from using
      an idealized version either of his or her parental objects as the "exciting
      object." The child therefore substitutes a grandiose view of himself or herself
      as the exciting object. This defense deflects external influences and replaces
      relationships with external objects with a closed internal world that is
      comprised of an admiring part-self basking in reflected love from its
      relationship with an exciting part-object. 

PMID- 24866162
TI  - "Oh, that I might be parted from my body": mirror perplexity and the
      nonrelational self.
AB  - Psychoanalytic models have a commonly held view of necessary and accurate
      mirroring in the dialectic of emergent and already formed aspects of the self.
      Mirroring-perplexity, however, is a cognitive and affective state found in a
      group of patients for whom reflective mirroring results in a dissociative rather
      than a unifying experience of body and mind. A review of the myth of Narcissus
      reveals that mirroring requires a relational mediation of self and mirror image
      through another. This ontological organization affectively links the simultaneous
      sense of being in the body and in the reflected image after experiencing a state
      of dyadic union. Clinical vignettes illustrate the effects of missing maternal
      relational response initially made evident in unmirrored self-representations in
      the transference.

PMID- 24866163
TI  - Analytic technique: a reconsideration of the concept.
AB  - Lipton's 1977 paper on "The Advantages of Freud's Technique ..." is taken as a
      starting point to reconsider the concept of analytic technique itself. How an
      analyst works may be construed in terms of rules of the analyst's behavior, of
      principles underlying the analyst's behavior, or of the analyst's attitude that
      shapes how he or she acts on technical principles. The author argues that the
      analyst's attitude while acting on technical principles is an integral part of
      analytic praxis, and that it is a function of the analyst's character. As such,
      it is not generalizable as a "technique," yet it is often the case that an
      analyst will rationalize his or her character traits and think of them as a
      reproducible "technique." This has important consequences for teaching and
      supervising. The author suggests that the very idea of a reproducible analytic
      technique may inhibit the analyst's development of his or her own analytic voice.
      Other aspects of theorizing may also represent a conceptual confusion between
      what is personal and characterological and what is generalizable. 

PMID- 24866168
TI  - Assessment of MAGE-A expression in resected non-small cell lung cancer in
      relation to clinicopathologic features and mutational status of EGFR and KRAS.
AB  - Non-small cell lung cancer (NSCLC) is a major public health problem, accounting
      for more cancer-related deaths than any other cancer. Both immunotherapy, based
      on the expression of tumor-specific antigens, and targeted therapy, based on the
      presence of oncogenic mutations, are under development for NSCLC. In this study,
      we analyzed the expression of MAGE-A, a cancer-testis antigen, in tumors from a
      cohort of patients with resected NSCLC with respect to their clinicopathologic
      characteristics and their mutational status for the EGFR and KRAS genes. We found
      MAGE-A expression by IHC in 43% of the tumors. MAGE-A expression was
      significantly more frequent in squamous tumors than in adenocarcinomas, did not
      correlate with disease stage, but was correlated significantly with high tumor
      grade and worse survival. EGFR and KRAS mutations were present in
      adenocarcinomas, but not in squamous tumors. Whereas the presence of EGFR
      mutations did not seem to affect survival, the presence of KRAS mutations was
      associated with early-stage disease and better survival. MAGE-A expression was
      absent from adenocarcinomas with KRAS mutations, but not significantly different
      in tumors with or without EGFR mutations. Together, the reported results provide
      guidance for the design of combination therapies in patients with NSCLC.

PMID- 24866166
TI  - Passive smoking exposure from partners as a risk factor for ER+/PR+ double
      positive breast cancer in never-smoking Chinese urban women: a hospital-based
      matched case control study.
AB  - BACKGROUND: The relationship between passive smoking exposure (PSE) and breast
      cancer risk is of major interest. OBJECTIVE: To evaluate the relationship between
      PSE from partners and breast cancer risk stratified by hormone-receptor (HR)
      status in Chinese urban women population. DESIGN: Hospital-based matched case
      control study. SETTING: Chinese urban breast cancer patients without current or
      previous active smoking history in China Medical University 1st Hospital,
      Liaoning Province, China between Jan 2009 and Nov 2009. PATIENTS: Each breast
      cancer patient was matched 1?1 with healthy controls by gender and age (+/-2
      years) from the same hospital. MEASUREMENTS: The authors used unconditional
      logistic regression analyses to estimate odds ratio for women with PSE from
      partners and breast cancer risk. RESULTS: 312 pairs were included in the study.
      Women who endured PSE had significantly increased risk of breast cancer (adjusted
      OR: 1.46; 95% CI: 1.05-2.03; P = 0.027), comparing with unexposed women. Women
      who exposed to >5 cigarettes/day also had significant increased risk (adjusted
      OR: 1.99; 95% CI: 1.28-3.10; P = 0.002), as were women exposed to passive smoke
      for 16-25 years (adjusted OR: 1.87 95% CI: 1.22-2.86; P = 0.004), and those
      exposed to > 4 pack-years (adjusted OR: 1.71 95% CI: 1.17-2.50; P = 0.004).
      Similar trends were significant for estrogen receptor (ER)/progesterone receptor
      (PR) double positive subgroup(adjusted OR: 1.71; 2.20; 1.99; 1.92, respectively),
      but not for ER+/PR-, ER-/PR+, or ER-/PR- subgroups. LIMITATIONS: limitations of
      the hospital-based retrospective study, lack of information on entire lifetime
      PSE and low statistical power. CONCLUSIONS: Our findings provide further evidence
      that PSE from partners contributes to increased risk of breast cancer, especially
      for ER/PR double positive breast cancer, in Chinese urban women.

PMID- 24866169
TI  - Programmed cell death ligand 1 expression in osteosarcoma.
AB  - Programmed cell death ligand 1 (PDL1, also known as B7H1) is a cell-surface
      protein that suppresses the cytotoxic CD8(+) T-cell-mediated immune response.
      PDL1 expression and its clinical relevance in sarcomas are not well understood.
      Therefore, we sought to measure RNA expression levels for PDL1 in 38 clinically
      annotated osteosarcoma tumor samples and aimed to determine if PDL1 expression
      correlates with clinical features and tumor-infiltrating lymphocytes (TIL).
      Quantitative real-time RT-PCR for PDL1 was optimized in 18 cell lines, of which 5
      were osteosarcoma derived. qRT-PCR results were validated via flow cytometry and
      immunohistochemistry (IHC) in select cell lines. Total RNA was isolated from 38
      human osteosarcoma samples for qRT-PCR analysis. Clinical data were sorted, and
      significance was determined by the Student t test. TILs were examined in patient
      samples by tissue microarray hematoxylin-eosin staining. We confirmed the
      constitutive PDL1 mRNA expression in cell lines by qRT-PCR, flow cytometry, and
      IHC. Across human osteosarcoma samples, PDL1 mRNA gene expression ranged over 4
      log (>5,000-fold difference). Relative expression levels were evaluated against
      clinical factors such as age/gender, metastasis, recurrence, chemotherapy,
      percentage of necrosis, and survival; no significant associations were
      identified. The presence of TILs was associated with high PDL1 expression (R(2) =
      0.37; P = 0.01). In summary, we developed an RNA-based assay to determine PDL1
      expression levels, and we show, for the first time, that high levels of PDL1 are
      expressed in a subset of osteosarcoma, and PDL1 expression is positively
      correlated with TILs. Multiple agents targeting PD1/PDL1 are in clinical
      development, and this may be a novel immunotherapeutic strategy for osteosarcoma
      clinical trials.

PMID- 24866171
TI  - Jocks versus geeks--the downside of genius?

PMID- 24866170
TI  - Differential methylation in CN-AML preferentially targets non-CGI regions and is
      dictated by DNMT3A mutational status and associated with predominant
      hypomethylation of HOX genes.
AB  - The extent and role of aberrant DNA methylation in promoter CpG islands (CGIs)
      have been extensively studied in leukemia and other malignancies. Still, CGIs
      represent only a small fraction of the methylome. We aimed to characterize genome
      wide differential methylation of cytogenetically normal AML (CN-AML) cells
      compared with normal CD34(+) bone marrow cells using the Illumina 450K
      methylation array. Differential methylation in CN-AML was most prominent in
      genomic areas far from CGIs, in so called open sea regions. Furthermore,
      differential methylation was specifically found in genes encoding transcription
      factors (TFs), with WT1 being the most differentially methylated TF. Among
      genetic mutations in AML, DNMT3A mutations showed the most prominent association
      with the DNA methylation pattern, characterized by hypomethylation of CGIs (as
      compared with DNMT3A wild type cases). The differential methylation in DNMT3A
      mutant cells vs. wild type cells was predominantly found in HOX genes, which were
      hypomethylated. These results were confirmed and validated in an independent CN
      AML cohort. In conclusion, we show that, in CN-AML, the most pronounced changes
      in DNA methylation occur in non-CGI regions and that DNMT3A mutations confer a
      pattern of global hypomethylation that specifically targets HOX genes.

PMID- 24866172
TI  - Using latent selection difference to model persistence in a declining population.
AB  - Population persistence is a direct measure of the viability of a population.
      Monitoring the distribution of declining populations or subpopulations over time
      can yield estimates of persistence, which we show can be modeled as a latent
      selection difference (LSD) contrasting attributes of sites where populations have
      persisted versus those that have not. Predicted persistence can be modeled with
      predictor covariates to identify factors correlated with species persistence. We
      demonstrate how to model persistence based on changes in occupancy that can
      include adjustments for detection probability. Using a known historical
      distribution of the western grebe (Aechmophorus occidentalis), we adapted methods
      originally developed for occupancy modeling to evaluate how environmental
      covariates including emergent vegetation and human developments have affected
      western grebe persistence in Alberta. The relative probability of persistence was
      correlated with the extent of shoreline bulrush (Scirpus lacustris), which is
      important vegetation for nesting cover. We also documented that western grebe
      populations were less likely to persist on lakes in the boreal forest, primarily
      located on the northern boundary of the species' range. Factors influencing
      occupancy were different than those determining persistence by western grebes;
      persistence and occupancy were not correlated. Persistence was more likely on
      lakes with recreational development, reflecting reliance by grebes on the larger,
      fish-bearing waterbodies that also are attractive for lakeshore development.
      Unfortunately, the correlation with recreational development on Alberta's lakes
      puts grebes at risk for loss of brood-rearing habitats--primary threats to
      altricial birds--if steps are not taken to prevent disturbance to bulrush stands.
      Identifying factors related to the persistence of a species--especially one in
      decline--is a fundamental step in conservation management.

PMID- 24866173
TI  - Potential factors affecting survival differ by run-timing and location: linear
      mixed-effects models of Pacific salmonids (Oncorhynchus spp.) in the Klamath
      River, California.
AB  - Understanding factors influencing survival of Pacific salmonids (Oncorhynchus
      spp.) is essential to species conservation, because drivers of mortality can vary
      over multiple spatial and temporal scales. Although recent studies have evaluated
      the effects of climate, habitat quality, or resource management (e.g., hatchery
      operations) on salmonid recruitment and survival, a failure to look at multiple
      factors simultaneously leaves open questions about the relative importance of
      different factors. We analyzed the relationship between ten factors and survival
      (1980-2007) of four populations of salmonids with distinct life histories from
      two adjacent watersheds (Salmon and Scott rivers) in the Klamath River basin,
      California. The factors were ocean abundance, ocean harvest, hatchery releases,
      hatchery returns, Pacific Decadal Oscillation, North Pacific Gyre Oscillation, El
      Nino Southern Oscillation, snow depth, flow, and watershed disturbance.
      Permutation tests and linear mixed-effects models tested effects of factors on
      survival of each taxon. Potential factors affecting survival differed among taxa
      and between locations. Fall Chinook salmon O. tshawytscha survival trends
      appeared to be driven partially or entirely by hatchery practices. Trends in
      three taxa (Salmon River spring Chinook salmon, Scott River fall Chinook salmon;
      Salmon River summer steelhead trout O. mykiss) were also likely driven by factors
      subject to climatic forcing (ocean abundance, summer flow). Our findings
      underscore the importance of multiple factors in simultaneously driving
      population trends in widespread species such as anadromous salmonids. They also
      show that the suite of factors may differ among different taxa in the same
      location as well as among populations of the same taxa in different watersheds.
      In the Klamath basin, hatchery practices need to be reevaluated to protect wild
      salmonids. 

PMID- 24866174
TI  - Hybrid materials science: a promised land for the integrative design of
      multifunctional materials.
AB  - For more than 5000 years, organic-inorganic composite materials created by men
      via skill and serendipity have been part of human culture and customs. The
      concept of "hybrid organic-inorganic" nanocomposites exploded in the second half
      of the 20th century with the expansion of the so-called "chimie douce" which led
      to many collaborations between a large set of chemists, physicists and
      biologists. Consequently, the scientific melting pot of these very different
      scientific communities created a new pluridisciplinary school of thought. Today,
      the tremendous effort of basic research performed in the last twenty years allows
      tailor-made multifunctional hybrid materials with perfect control over
      composition, structure and shape. Some of these hybrid materials have already
      entered the industrial market. Many tailor-made multiscale hybrids are
      increasingly impacting numerous fields of applications: optics, catalysis,
      energy, environment, nanomedicine, etc. In the present feature article, we
      emphasize several fundamental and applied aspects of the hybrid materials field:
      bioreplication, mesostructured thin films, Lego-like chemistry designed hybrid
      nanocomposites, and advanced hybrid materials for energy. Finally, a few
      commercial applications of hybrid materials will be presented. 

PMID- 24866175
TI  - The activation of representative emotional verbal contexts interacts with
      vertical spatial axis.
AB  - Several experimental studies have shown that there exists an association between
      emotion words and the vertical spatial axis. However, the specific conditions
      under which this conceptual-physical interaction emerges are still unknown, and
      no study has been devised to test whether longer linguistic units than words can
      lead to a mapping of emotions on vertical space. In Experiment 1, Spanish and
      Colombian participants performed a representative verbal emotional contexts
      production task (RVEC task) requiring participants to produce RVEC for the
      emotions of joy, sadness, surprise, anger, fear, and disgust. The results showed
      gender and cultural differences regarding the average number of RVEC produced.
      The most representative contexts of joy and sadness obtained in Experiment 1 were
      used in Experiment 2 in a novel spatial-emotional congruency verification task
      (SECV task). After reading a sentence, the participants had to judge whether a
      probe word, displayed in either a high or low position on the screen, was
      congruent or incongruent with the previous sentence. The question was whether the
      emotion induced by the sentence could modulate the responses to the probes as a
      function of their position in a vertical axis by means of a metaphorical
      conceptual-spatial association. Overall, the results indicate that a mapping of
      emotions on vertical space can occur for linguistic units larger than words, but
      only when the task demands an explicit affective evaluation of the target. 

PMID- 24866176
TI  - Contact-free palm-vein recognition based on local invariant features.
AB  - Contact-free palm-vein recognition is one of the most challenging and promising
      areas in hand biometrics. In view of the existing problems in contact-free palm
      vein imaging, including projection transformation, uneven illumination and
      difficulty in extracting exact ROIs, this paper presents a novel recognition
      approach for contact-free palm-vein recognition that performs feature extraction
      and matching on all vein textures distributed over the palm surface, including
      finger veins and palm veins, to minimize the loss of feature information. First,
      a hierarchical enhancement algorithm, which combines a DOG filter and histogram
      equalization, is adopted to alleviate uneven illumination and to highlight vein
      textures. Second, RootSIFT, a more stable local invariant feature extraction
      method in comparison to SIFT, is adopted to overcome the projection
      transformation in contact-free mode. Subsequently, a novel hierarchical
      mismatching removal algorithm based on neighborhood searching and LBP histograms
      is adopted to improve the accuracy of feature matching. Finally, we rigorously
      evaluated the proposed approach using two different databases and obtained 0.996%
      and 3.112% Equal Error Rates (EERs), respectively, which demonstrate the
      effectiveness of the proposed approach. 

PMID- 24866177
TI  - Cation-exchanged SAPO-34 for adsorption-based hydrocarbon separations:
      predictions from dispersion-corrected DFT calculations.
AB  - The influence of the nature of the cation on the interaction of the
      silicoaluminophosphate SAPO-34 with small hydrocarbons (ethane, ethylene,
      acetylene, propane, propylene) is investigated using periodic density-functional
      theory calculations including a semi-empirical dispersion correction (DFT-D).
      Initial calculations are used to evaluate which of the guest-accessible cation
      sites in the chabazite-type structure is energetically preferred for a set of ten
      cations, which comprises four alkali metals (Li(+), Na(+), K(+), Rb(+)), three
      alkaline earth metals (Mg(2+), Ca(2+), Sr(2+)), and three transition metals
      (Cu(+), Ag(+), Fe(2+)). All eight cations that are likely to be found at the SII
      site (centre of a six-ring) are then included in the following investigation,
      which studies the interaction with the hydrocarbon guest molecules. In addition
      to the interaction energies, some trends and peculiarities regarding the
      adsorption geometries are analysed, and electron density difference plots
      obtained from the calculations are used to gain insights into the dominant
      interaction types. In addition to dispersion interactions, electrostatic and
      polarisation effects dominate for the main group cations, whereas significant
      orbital interactions are observed for unsaturated hydrocarbons interacting with
      transition metal (TM) cations. The differences between the interaction energies
      obtained for pairs of hydrocarbons of interest (such as ethylene-ethane and
      propylene-propane) deliver some qualitative insights: if this energy difference
      is large, it can be expected that the material will exhibit a high selectivity in
      the adsorption-based separation of alkene-alkane mixtures, which constitutes a
      problem of considerable industrial relevance. While the calculations show that TM
      exchanged SAPO-34 materials are likely to exhibit a very high preference for
      alkenes over alkanes, the strong interaction may render an application in
      industrial processes impractical due to the large amount of energy required for
      regeneration. In this respect, SAPOs exchanged with alkaline earth cations could
      provide a better balance between selectivity and energy cost of regeneration. 

PMID- 24866178
TI  - Inhibition of endometrial cancer by n-3 polyunsaturated fatty acids in
      preclinical models.
AB  - Although preclinical and epidemiologic studies have shown the importance of n-3
      polyunsaturated fatty acids (PUFA) in the prevention of hormone-responsive
      cancers such as breast cancer, evidence of the association between n-3 PUFAs and
      endometrial cancer risk is limited and no previous study has examined the effect
      of n-3 PUFAs on endometrial cancer in cellular and animal models. In this study,
      we demonstrated that docosahexenoic acid (DHA) dose- and time-dependently
      inhibited endometrial cancer cell proliferation, colony formation, and migration
      and promoted apoptosis. Dietary n-3 PUFAs efficiently prevented endometrial
      cancer cell growth in xenograft models. Moreover, ectopic expression of fat-1, a
      desaturase, catalyzed the conversion of n-6 to n-3 PUFAs and produced n-3 PUFAs
      endogenously, also suppressed endometrial tumor cell growth and migration, and
      potentiated apoptosis in endometrial cancer cell lines. Interestingly, implanted
      endometrial cancer cells were unable to grow in fat-1 transgenic SCID mice.
      Further study revealed that mTOR signaling, which plays an essential role in cell
      proliferation and endometrial tumorigenesis, is a target of n-3 PUFAs. Exogenous
      or endogenous n-3 PUFAs efficiently suppressed both mTOR complex 1 (mTORC1) and
      mTORC2 in vitro and in vivo. Moreover, both dietary n-3 PUFAs and transgenic
      expression of fat-1 in mice effectively repressed mTORC1/2 signaling and
      endometrial growth elicited by unopposed estrogen. Taken together, our findings
      provide comprehensive preclinical evidences that n-3 PUFAs efficiently prevent
      endometrial cancer and establish mTORC1/2 as a target of n-3 PUFAs.

PMID- 24866179
TI  - Myeloid lineage-specific deletion of antioxidant system enhances tumor
      metastasis.
AB  - Oxidative stress accelerates the pathogenesis of a number of chronic diseases
      including cancer growth and its metastasis. Transcription factor NF-E2-related
      factor-2 (Nrf2), which regulates the cellular defense system against oxidative
      stress, elicits essential protection against chemical-induced carcinogenic
      insults. We recently demonstrate that the systemic deletion of Nrf2 leads to an
      increased susceptibility to cancer metastasis, which is associated with aberrant
      reactive oxygen species (ROS) accumulation in myeloid-derived suppressor cells
      (MDSC). However, it remains elusive whether cellular antioxidant defense system
      in the myeloid lineage cells plays indispensable roles for metastatic cancer
      progression. We herein found that myeloid lineage-specific Nrf2-deficient mice
      exhibited an increased susceptibility to pulmonary metastasis of the mouse Lewis
      lung carcinoma cells, and ROS level was more highly elevated in MDSCs of cancer
      bearing Nrf2-deficient mice. Similarly, myeloid lineage-specific deletion of
      selenocysteine-tRNA gene (Trsp), which is essential for synthesis of antioxidant
      selenoenzymes, resulted in increased number of metastatic nodules along with ROS
      accumulation in MDSCs of cancer-bearing mice. These results thus indicate that
      the antioxidant systems directed by Nrf2 and selenoenzymes contribute to the
      clearance of ROS in MDSCs, efficiently preventing cancer cell metastasis.
      Consistent with this notion, a synthetic triterpenoid 1-[2-cyano-3,12-dioxooleana
      1,9(11)-dien-28-oyl] imidazole (CDDO-Im), a potent Nrf2 inducer, attenuated the
      ROS production in MDSCs, and thereafter reduced metastatic nodules. Taken
      together, this study provides compelling lines of evidence that Nrf2 inducer
      retains therapeutic efficacy against cancer cell metastasis.

PMID- 24866180
TI  - Is Europe 'giving in to baby markets?' Reproductive tourism in Europe and the
      gradual erosion of existing legal limits to reproductive markets.
AB  - The main question in this article is how national legal orders in Europe, given
      their often restrictive laws on reproductive markets and assisted reproductive
      technologies (ARTs), are currently responding and should respond to reproductive
      tourism, in light of the fact that access to foreign reproductive markets seems
      to be making these national laws 'merely symbolic'. Although many national
      governments have finally managed after many years of political and legal
      struggles to establish a carefully balanced legal framework for the regulation of
      these often ethically and religiously sensitive matters, ironically reproductive
      travel seems to be turning national reproductive laws into a dead letter.
      Currently, as a reaction to these developments, new legal strategies are being
      proposed and explored. Within the European context, the view is gaining ground
      that laws that curb international reproductive markets and their accompanying
      streams of fertility tourism have become ineffective, meaningless, and even
      harmful. As a result, a certain tendency towards tolerance of reproductive
      markets and reproductive travel can be detected in both politics and academia.
      According to this line of reasoning, restrictive and prohibitive legislation
      should be replaced by more pragmatic policies that take the realities of
      reproductive markets as a starting point. From this perspective, the legal
      restrictions within the country of origin, rather than the lack of regulation in
      the country of destination, should be regarded as the core of the problem. As a
      result, an increasing number of scholars and policy makers are arguing for more
      lenient national policies towards ARTs, hoping to thereby remove the main
      incentive for aspiring parents to resort to foreign reproductive services. This
      emerging pragmatic strategy of tolerance towards reproductive tourism and
      international reproductive markets rests on three arguments, which are each
      critically examined in this article. Although these arguments offer valuable
      insights, several disadvantages and weaknesses tend to be overlooked. The
      critical examination of these pragmatic arguments is followed by a plea for a
      more positive understanding and recognition of the symbolic dimensions of
      reproductive legislation. It is argued that ART laws also have an important
      communicative, expressive and anthropological meaning and function, which surpass
      these laws' practical effectiveness. Alternatively, policies based on the
      pragmatic tolerance of reproductive markets show significant shortcomings, which
      also need to be taken into consideration by national governments when evaluating
      existing ART laws. 

PMID- 24866181
TI  - Beyond pragmatism: defending the 'bright line' of birth.
AB  - It is usually accepted by ethicists that birth does not alter moral status.
      Rather, it is thought that the rule according full legal rights at birth is
      pragmatic. Pragmatic reasoning is vulnerable to competing practical concerns and
      stronger moral principles. This 'bright line' has therefore been criticised both
      by those who believe personhood begins before birth and those who believe it
      begins afterward. In particular, a recent article by Giubilini and Minerva puts
      forward both pragmatic and moral arguments in favour of permitting infanticide,
      and the New South Wales Court of Criminal Appeal has suggested there is a strong
      case for abandoning the bright line (R v Iby (2005) 63 NSWLR 278). If we desire
      to defend current legal doctrine against such criticism, a medical and
      philosophical basis for the law should be articulated. This article suggests such
      a medical and philosophical basis. It argues that both the multiplicity of
      biological changes occurring in the neonate at birth and the extrauterine context
      (the world) provide a justification for the distinction drawn at law between
      abortion and infanticide. With reference to Robert Nozick's 'experience machine'
      thought-experiment and elements of phenomenological philosophy, it advances two
      propositions to explain the status-changing nature of the neonate's emergence out
      of the womb. First, that expressing sentience in the world is essential for the
      attainment of personhood. Second, that having become a person, the harm in
      killing is disruption of this engagement with the world and the reduction from
      personhood to non-existence. This is the distinction between a neonate's death
      and the termination of a foetus, underscoring the qualitative difference between
      the two sides of the bright line drawn in law. 

PMID- 24866183
TI  - Nature plants.
AB  - We welcome our new sister journal Nature Plants and the increased commitment to
      the plant science community that it represents. This is an opportunity for Nature
      Genetics to emphasize the use of genetic and genomic tools and resources in
      discovering new plant biology and solving major agricultural challenges.

PMID- 24866184
TI  - Turtle ghrelin.

PMID- 24866182
TI  - The effect of ageing on ocular blood flow, oxygen tension and retinal function
      during and after intraocular pressure elevation.
AB  - PURPOSE: To investigate the effect of ageing on the recovery of ocular blood
      flow, intravitreal oxygen tension and retinal function during and after
      intraocular pressure (IOP) elevation. METHODS: Long Evans rats (3- and 14-month
      old) underwent acute stepwise IOP elevation from 10 to 120 mmHg (5 mmHg steps
      each 3 minutes). IOP was then returned to baseline and recovery was monitored for
      2 hours. Photopic electroretinograms (ERG) were recorded at each IOP step during
      stress and at each minute during recovery. Ocular blood flow and vitreal oxygen
      tension (pO2) were assayed continuously and simultaneously using a combined laser
      Doppler flow meter (LDF) and an oxygen sensitive fibre-optic probe, respectively.
      The combined sensor was placed in the vitreous chamber, proximal to the retina.
      Data were binned into 3 minute intervals during stress and 1 min intervals during
      recovery. Recovery data was described using a bi-logistic function. RESULTS: Rats
      of both ages showed similar susceptibility to IOP elevation, with pO2 showing a
      closer relationship to ERG than LDF. During recovery, both ages showed a
      distinctive two-phased recovery for all three measures with the exception of the
      LDF in 3-month-old rats, which showed only 1 phase. In all animals, LDF recovered
      fastest (<1 minute), followed by pO2 (<10 minute) and ERG (>1 hour). 14-month-old
      rats showed surprisingly faster and greater LDF recovery compared to the younger
      group, with similar levels of pO2 recovery. However, the ERG in these middle-aged
      animals did not fully recover after two hours, despite showing no difference in
      susceptibility to IOP during stress compared to the young group. CONCLUSIONS:
      Young and middle-aged eyes showed similar susceptibility to IOP elevation in
      terms of pO2, LDF and ERG. Despite this lack of difference during stress, older
      eyes did not completely recover function, suggesting a more subtle age-related
      susceptibility to IOP.

PMID- 24866185
TI  - Turtle ghrelin.

PMID- 24866186
TI  - Turtle ghrelin.

PMID- 24866187
TI  - PARK2 orchestrates cyclins to avoid cancer.
AB  - Proper control of cyclin-dependent kinases ensures coordinated cell cycle
      progression and guards against tumorigenesis. A new study identifies the PARK2 E3
      ubiquitin ligase as an important coordinator of G1/S-phase cyclin turnover and
      explains how mutations targeting this key cell cycle regulatory node contribute
      to a range of cancers. 

PMID- 24866188
TI  - Cross-talk between imprinted loci in Prader-Willi syndrome.
AB  - Prader-Willi syndrome (PWS) is caused by loss of paternally expressed genes at an
      imprinted locus on chromosome 15, including the long noncoding RNA IPW. A new
      study identifies a critical role for IPW in modulating the expression of
      maternally expressed genes in trans, which has important implications for the
      understanding of imprinted gene networks. 

PMID- 24866189
TI  - Exploring new models of easiRNA biogenesis.
AB  - Although silent transposons in plants can be reactivated by stress or during
      development, their potential deleterious effects are prevented by transposon
      derived epigenetically activated small interfering RNAs (easiRNAs). A new study
      shows how serendipitous interactions between reactivated transposons and
      endogenous microRNAs might initiate easiRNA biogenesis, establishing an
      unexpected link between these two classes of silencing small RNAs. 

PMID- 24866199
TI  - Rituximab: how approval history is reflected by a corresponding patent filing
      strategy.
AB  - Because drug development is not a static process, a drug's market authorisation
      may change over time. In many cases, the number of indications for which a drug
      is approved increases. Because this facet of drug development also comes at
      significant costs, a corresponding patent filing strategy is required to protect
      these investments. The strategy as applied to rituximab, which is approved for a
      variety of indications, is discussed in this review. 

PMID- 24866200
TI  - Cost of treatment in a US commercially insured, HIV-1-infected population.
AB  - OBJECTIVE: Recent treatment patterns and cost data associated with HIV in the
      United States are limited. This study assessed first-line persistence and
      healthcare costs of HIV-1 in patients by treatment line and CD4 cell count.
      METHODS: MarketScan Commercial Claims and Encounters Database (2007-2011) and Lab
      Database (2007-2010) were used to construct two HIV-1 cohorts: 1) newly treated
      HIV-1-infected patients with >=6 months' continuous enrollment prior to first
      third-agent drug claim (Newly Treated Cohort) and 2) CD4 cell count test results
      (CD4 Measurements Cohort). All patients were >=18 years old and without hepatitis
      co-infection. The Kaplan-Meier method was used to measure treatment switch rates.
      Generalized linear models (gamma distribution, log link) were used to compare
      healthcare costs by treatment line and CD4 cell count controlling for potential
      confounders. RESULTS: Newly treated patients (n = 8,617) had mean age of 41, 82%
      were male, and 20% had experienced AIDS-defining events at baseline. Over 20% of
      newly treated patients switched initial treatment regimen within 2 years. Average
      unadjusted (and covariate-adjusted) total healthcare cost/year was $33,674
      ($28,861) for first-line, $39,191 ($35,805) for second-line, and $39,882
      ($40,804) for third-line treatment. Covariate-adjusted costs of care on second-
      and third-line treatments were significantly more expensive than first-line
      treatment (24% [p<0.001] and 41% [p = 0.006] higher, respectively). The CD4
      Measurements Cohort included 803 CD4 measurements (mean age 49, 76% male, 8%
      experienced an AIDS-defining event). Costs associated with CD4 measurements <100
      cells/uL were 92% higher than those with >350 cells/uL (p<0.001). For higher CD4
      cell counts, the majority of expenditures were for antiretrovirals (64% of total
      for CD4 >350 cells/uL). CONCLUSIONS: Despite modern advances in antiretroviral
      therapy and medical care, direct medical costs of HIV-1-infected patients
      increase after treatment switch and with lower CD4 counts, consistent with
      previous costing studies.

PMID- 24866201
TI  - Age-dependent effects on the treatment response of natalizumab in MS patients.
AB  - BACKGROUND: Natalizumab is approved for treatment of active forms of relapsing
      remitting multiple sclerosis (MS) based on a pivotal phase III study comprising
      patients aged 18-50 years. The effect of natalizumab has not been specifically
      studied in older patients. OBJECTIVE: We analyzed age-dependent effects on
      treatment-related outcome measures in 1872 patients, 189 of whom were aged 50 or
      more, included in the Swedish post-marketing natalizumab surveillance program.
      METHODS: In three MS centers registry data for patients aged >50 years were
      validated. RESULTS: At baseline older patients had longer disease duration,
      higher Expanded Disability Status Scale (EDSS) and lower Symbol Digit Modality
      Test (SDMT) scores than younger patients. The influence from natalizumab on
      outcome measures was significantly reduced and 18.7% of patients >50 years
      stopped treatment for lack of effect compared to 7.7% in the younger age group.
      At baseline, the cerebrospinal fluid levels of the chemokine CXCL13 and the
      leukocyte cell count were negatively correlated with age in a smaller subgroup of
      patients. CONCLUSION: These results were in agreement with previous findings
      suggesting that inflammation is more pronounced in younger patients and therefore
      the beneficial effects of potent anti-inflammatory treatments are subsiding with
      older ages.

PMID- 24866202
TI  - Relapsing inappropriate antidiuretic hormone secretion in an anti-aquaporin-4
      antibody positive paediatric patient.
AB  - Paediatric patients with the syndrome of an inappropriate antidiuretic hormone
      secretion (SIADH), as a manifestation of inflammatory demyelinating disorders of
      the central nervous system, have been rarely described until now, in only a few
      cases of neuromyelitis optica spectrum disorders (NMOSDs). We present a case of
      relapsing SIADH associated with NMOSD, in an anti-aquaporin-4 antibody positive
      14-year-old girl, who is, to our best knowledge, the first reported paediatric
      patient with relapsing SIADH and NMOSD. Additionally, our case further supports
      the notion that paediatric encephalomyelitis associated with SIADH should suggest
      the diagnosis of NMOSD. 

PMID- 24866203
TI  - Fingolimod-induced asthma deterioration in a patient with relapsing-remitting
      multiple sclerosis.

PMID- 24866204
TI  - Multistate outbreak of Salmonella enterica serotype enteritidis infection
      associated with pet guinea pigs.
AB  - Salmonella causes about one million illnesses annually in the United States.
      Although most infections result from foodborne exposures, animal contact is an
      important mode of transmission. We investigated a case of Salmonella enterica
      serotype Enteritidis (SE) sternal osteomyelitis in a previously healthy child who
      cared for two recently deceased guinea pigs (GPs). A case was defined as SE
      pulsed-field gel electrophoresis (PFGE) XbaI pattern JEGX01.0021, BlnI pattern
      JEGA26.0002 (outbreak strain) infection occurring during 2010 in a patient who
      reported GP exposure. To locate outbreak strain isolates, PulseNet and the US
      Department of Agriculture National Veterinary Service Laboratories (NVSL)
      databases were queried. Outbreak strain isolates underwent multilocus variable
      number tandem repeat analysis (MLVA). Traceback and environmental investigations
      were conducted at homes, stores, and breeder or broker facilities. We detected 10
      cases among residents of eight states and four NVSL GP outbreak strain isolates.
      One patient was hospitalized; none died. The median patient age was 9.5 (range, 1
      61) years. Among 10 patients, two purchased GPs at independent stores, and three
      purchased GPs at different national retail chain (chain A) store locations; three
      were chain A employees and two reported GP exposures of unknown characterization.
      MLVA revealed four related patterns. Tracebacks identified four distributors and
      92 sources supplying GPs to chain A, including one breeder potentially supplying
      GPs to all case-associated chain A stores. All environmental samples were
      Salmonella culture-negative. A definitive SE-contaminated environmental source
      was not identified. Because GPs can harbor Salmonella, consumers and pet industry
      personnel should be educated regarding risks.

PMID- 24866205
TI  - The impact of housing displacement on the mental health of low-income parents
      after Hurricane Katrina.
AB  - Previous studies in the aftermath of natural disasters have demonstrated
      relationships between four dimensions of displacement - geographic distance from
      the predisaster community, type of postdisaster housing, number of postdisaster
      moves, and time spent in temporary housing - and adverse psychological outcomes.
      However, to date no study has explored how these dimensions operate in tandem.
      The literature is further limited by a reliance on postdisaster data. We
      addressed these limitations in a study of low-income parents, predominantly non
      Hispanic Black single mothers, who survived Hurricane Katrina and who completed
      pre and postdisaster assessments (N = 392). Using latent profile analysis, we
      demonstrated three profiles of displacement experiences within the sample: (1)
      returned, characterized by return to a predisaster community; (2) relocated,
      characterized by relocation to a new community, and (3) unstably housed,
      characterized by long periods in temporary housing and multiple moves. Using
      regression analyses, we assessed the relationship between displacement profiles
      and three mental health outcomes (general psychological distress, posttraumatic
      stress, and perceived stress), controlling for predisaster characteristics and
      mental health indices and hurricane-related experiences. Relative to participants
      in the returned profile, those in the relocated profile had significantly higher
      general psychological distress and perceived stress, and those in the unstably
      housed profile had significantly higher perceived stress. Based on these results,
      we suggest interventions and policies that reduce postdisaster housing
      instability and prioritize mental health services in communities receiving
      evacuees.

PMID- 24866206
TI  - Migration and HIV risk: life histories of Mexican-born men living with HIV in
      North Carolina.
AB  - Latino men in the Southeastern USA are disproportionately affected by HIV, but
      little is known about how the migration process influences HIV-related risk. In
      North Carolina, a relatively new immigrant destination, Latino men are
      predominantly young and from Mexico. We conducted 31 iterative life history
      interviews with 15 Mexican-born men living with HIV. We used holistic content
      narrative analysis methods to examine HIV vulnerability in the context of
      migration and to identify important turning points. Major themes included the
      prominence of traumatic early-life experiences, migration as an ongoing process
      rather than a finite event, and HIV diagnosis as a final turning point in
      migration trajectories. Findings provide a nuanced understanding of HIV
      vulnerability throughout the migration process and have implications including
      the need for bi-national HIV-prevention approaches, improved outreach around
      early testing and linkage to care, and attention to mental health. 

PMID- 24866207
TI  - The effects of caregiver emotional stress on the depressive symptomatology of the
      care recipient.
AB  - OBJECTIVES: Depression is a leading mental health issue affecting elderly
      individuals worldwide. Previous research widely neglects caregiver emotional
      stress as a probable contributing factor of depression in the elderly. This study
      investigated caregiver emotional stress as a chronic life stressor of an elderly
      care recipient using the life stress paradigm as the theoretical foundation.
      METHODS: The relationships between caregiver emotional stress and care receiver
      depressive symptoms, as well as other social and psychological mediation factors,
      were investigated using the 2004 wave of the National Long-Term Care Study
      (NLTCS). The NLTCS is a nationally representative longitudinal study used to
      identify frail and disabled elderly Medicare recipients living in the United
      States. The analytic sample of this study included 1340 caregiver-care receiver
      dyads who were asked a series of questions concerning their mental health (i.e.
      emotional stress and depressive symptoms), as well as the availability of social
      and psychological resources. RESULTS: Overall, the results showed that high
      levels of emotional stress reported by the caregiver were associated with a
      higher likelihood of the disabled care receiver reporting depressive symptoms.
      CONCLUSION: The findings of this investigation point to the importance of
      studying caregivers and care receivers as dyads as the stress associated with the
      caregiving role affects each member.

PMID- 24866208
TI  - Immunoglobulin-free light chain monomer-dimer patterns help to distinguish
      malignant from premalignant monoclonal gammopathies: a pilot study.
AB  - Multiple myeloma (MM) and AL amyloidosis (AL) are two malignant forms of
      monoclonal gammopathies. For the purposes of prognosis and treatment, it is
      important to distinguish these diseases from the premalignant forms of monoclonal
      gammopathies, such as monoclonal gammopathy of unknown significance (MGUS) and
      smoldering myeloma (SMM). Routine serum/urine tests for monoclonal protein are
      insufficient for differential diagnosis. Thus, invasive procedures, such as
      tissue aspiration or biopsy, are applied. In this study, we aimed at
      characterization of serum-free light chain (FLC) monomer-dimer patterns to
      distinguish the malignant from the premalignant forms of monoclonal gammopathies.
      A quantitative Western blotting was applied to estimate the FLC monomer and dimer
      levels in AL, MM, MGUS, and SMM patients, and in control subjects (healthy
      individuals and patients with AA amyloidosis). AL and MM patients displayed an
      abnormally increased dimerization of monoclonal FLC, accompanied by higher
      clonality values of FLC dimers, as compared to that of monomers. These
      abnormalities of FLC patterns were not observed in patients with MGUS, SMM, AA
      amyloidosis, and healthy individuals. Analysis of FLC patterns helped to
      differentiate AL and MM from MGUS and SMM, a goal difficult to achieve using
      routine serum tests. Also, our technique might serve as a complimentary
      diagnostic tool in the cases with suspected AL amyloidosis, where the diagnosis
      of MM is excluded, while the results of amyloid typing by routine
      immunohistochemical techniques are inconclusive.

PMID- 24866212
TI  - Functional gallbladder disorder: an increasingly common diagnosis.

PMID- 24866209
TI  - Barriers to provider-initiated testing and counselling for children in a high HIV
      prevalence setting: a mixed methods study.
AB  - BACKGROUND: There is a substantial burden of HIV infection among older children
      in sub-Saharan Africa, the majority of whom are diagnosed after presentation with
      advanced disease. We investigated the provision and uptake of provider-initiated
      HIV testing and counselling (PITC) among children in primary health care
      facilities, and explored health care worker (HCW) perspectives on providing HIV
      testing to children. METHODS AND FINDINGS: Children aged 6 to 15 y attending six
      primary care clinics in Harare, Zimbabwe, were offered PITC, with guardian
      consent and child assent. The reasons why testing did not occur in eligible
      children were recorded, and factors associated with HCWs offering and
      children/guardians refusing HIV testing were investigated using multivariable
      logistic regression. Semi-structured interviews were conducted with clinic nurses
      and counsellors to explore these factors. Among 2,831 eligible children, 2,151
      (76%) were offered PITC, of whom 1,534 (54.2%) consented to HIV testing. The main
      reasons HCWs gave for not offering PITC were the perceived unsuitability of the
      accompanying guardian to provide consent for HIV testing on behalf of the child
      and lack of availability of staff or HIV testing kits. Children who were
      asymptomatic, older, or attending with a male or a younger guardian had
      significantly lower odds of being offered HIV testing. Male guardians were less
      likely to consent to their child being tested. 82 (5.3%) children tested HIV
      positive, with 95% linking to care. Of the 940 guardians who tested with the
      child, 186 (19.8%) were HIV-positive. CONCLUSIONS: The HIV prevalence among
      children tested was high, highlighting the need for PITC. For PITC to be
      successfully implemented, clear legislation about consent and guardianship needs
      to be developed, and structural issues addressed. HCWs require training on
      counselling children and guardians, particularly male guardians, who are less
      likely to engage with health care services. Increased awareness of the risk of
      HIV infection in asymptomatic older children is needed.

PMID- 24866210
TI  - Therapeutic efficacy of cardiosphere-derived cells in a transgenic mouse model of
      non-ischaemic dilated cardiomyopathy.
AB  - AIM: Cardiosphere-derived cells (CDCs) produce regenerative effects in the post
      infarct setting. However, it is unclear whether CDCs are beneficial in non
      ischaemic dilated cardiomyopathy (DCM). We tested the effects of CDC
      transplantation in mice with cardiac-specific Galphaq overexpression, which
      predictably develop progressive cardiac dilation and failure, with accelerated
      mortality. METHODS AND RESULTS: Wild-type mouse CDCs (10(5) cells) or vehicle
      only were injected intramyocardially in 6-, 8-, and 11-week-old Galphaq mice.
      Cardiac function deteriorated in vehicle-treated mice over 3 months of follow-up,
      accompanied by oxidative stress, inflammation and adverse ventricular
      remodelling. In contrast, CDCs preserved cardiac function and volumes, improved
      survival, and promoted cardiomyogenesis while blunting Galphaq-induced oxidative
      stress and inflammation in the heart. The mechanism of benefit is indirect, as
      long-term engraftment of transplanted cells is vanishingly low. CONCLUSIONS:
      Cardiosphere-derived cells reverse fundamental abnormalities in cell signalling,
      prevent adverse remodelling, and improve survival in a mouse model of DCM. The
      ability to impact favourably on disease progression in non-ischaemic heart
      failure heralds new potential therapeutic applications of CDCs.

PMID- 24866213
TI  - Evidence to guide measles immunization recommendations.

PMID- 24866214
TI  - Enlarging, painful nodule under the toenail.

PMID- 24866215
TI  - Surgical and nonsurgical management of gallstones.
AB  - Cholelithiasis, or gallstones, is one of the most common and costly of all the
      gastrointestinal diseases. The incidence of gallstones increases with age. At
      risk populations include persons with diabetes mellitus, persons who are obese,
      women, rapid weight cyclers, and patients on hormone therapy or taking oral
      contraceptives. Most patients are asymptomatic; gallstones are discovered
      incidentally during ultrasonography or other imaging of the abdomen. Asymptomatic
      patients have a low annual rate of developing symptoms (about 2% per year). Once
      symptoms appear, the usual presentation of uncomplicated gallstones is biliary
      colic, caused by the intermittent obstruction of the cystic duct by a stone. The
      pain is characteristically steady, is usually moderate to severe in intensity, is
      located in the epigastrium or right upper quadrant of the abdomen, lasts one to
      five hours, and gradually subsides. If pain persists with the onset of fever or
      high white blood cell count, it should raise suspicion for complications such as
      acute cholecystitis, gallstone pancreatitis, and ascending cholangitis.
      Ultrasonography is the best initial imaging study for most patients, although
      additional imaging studies may be indicated. The management of acute biliary
      colic mainly involves pain control with nonsteroidal anti-inflammatory drugs or
      narcotic pain relievers. Oral dissolution therapy is usually minimally successful
      and used only if the patient cannot undergo surgery. Laparoscopic cholecystectomy
      remains the surgical choice for symptomatic and complicated gallstones, with a
      shorter hospital stay and shorter convalescence period than open cholecystectomy.
      Percutaneous cholecystostomy is an alternative for patients who are critically
      ill with gallbladder empyema and sepsis. 

PMID- 24866217
TI  - Complications of adjustable gastric banding surgery for obesity.
AB  - Laparoscopic adjustable gastric banding procedures have a favorable risk-benefit
      profile and are increasingly important as part of the overall management of
      obesity. These procedures are effective at inducing weight loss and improving
      comorbid conditions, including diabetes mellitus, hypertension, and sleep apnea.
      Laparoscopic adjustable gastric banding has several typical complications, and
      family physicians should recognize these as part of a team-based approach to the
      management of obesity. Gastric band slippage, port or tubing malfunction, stomal
      obstruction, band erosion, pouch dilation, and port infection are examples of
      complications that may occur after laparoscopic adjustable gastric banding. Upper
      gastrointestinal tract imaging is often required to diagnose these complications.
      Some complications can be managed in the primary care setting through behavioral
      diet modification or removal of fluid from the band (band deflation); however,
      other complications require surgical repair or removal of the band. 

PMID- 24866223
TI  - FPIN's clinical inquiries: treatment of jellyfish envenomation.

PMID- 24866224
TI  - Gallstones.

PMID- 24866216
TI  - Neglected parasitic infections: what every family physician needs to know.
AB  - Neglected parasitic infections, including Chagas disease, toxocariasis,
      cysticercosis, and toxoplasmosis, affect millions of persons in the United
      States. Relatively few resources have been devoted to surveillance, prevention,
      and treatment of these diseases. Chagas disease primarily affects Latin American
      immigrants and can cause heart failure and death if not treated. Immediate
      antiparasitic treatment is indicated for most patients with acute Chagas disease.
      Treatment is recommended for patients younger than 18 years who have chronic
      Chagas disease and is generally recommended for adults younger than 50 years who
      do not have advanced cardiomyopathy; treatment decisions for other patients
      should be made on an individual basis. Toxocariasis primarily affects children
      and can cause gastrointestinal, respiratory, and ophthalmologic disease.
      Treatment options include albendazole and mebendazole. Patients with ocular
      infection require referral to an ophthalmologist. Neurocysticercosis, a form of
      cysticercosis, is the most common infectious cause of seizures in some parts of
      the United States. Initial treatment should focus on symptom control. Humans
      generally acquire toxoplasmosis by eating undercooked contaminated meat or
      ingesting things that have been contaminated with cat feces. Congenital infection
      can result in miscarriage or adverse fetal effects. Treatment is recommended for
      immunosuppressed persons, pregnant women, and immunocompetent persons with severe
      symptoms. 

PMID- 24866226
TI  - The aqueduct.

PMID- 24866225
TI  - Preventive effect of Monascus-fermented products enriched with ubiquinones on
      type 2 diabetic rats induced by a high-fructose plus high-fat diet.
AB  - The aim of the present study was to investigate whether the aqueous extract of
      Monascus-fermented grains (MFGEs) enriched with ubiquinones (Coenzyme Qs,
      CoQ9+CoQ10) alleviates high-fructose (60%) plus high-fat (20%) diet (HFD)-induced
      hyperglycemia and hepatic oxidative stress in male Sprague-Dawley rats. Animals
      were fed HFD for 16 weeks and orally administered with MFGEs (300 mg/kg/day) or
      atorvastatin (20 mg/kg/day) for the last 4 weeks of the study. HFD-fed rats
      exhibited hyperglycemia, hyperinsulinemia, impaired glucose tolerance, and
      impaired insulin sensitivity. MFGE treatment prevented the increase in glucose
      levels and index of insulin resistance in the HFD-induced diabetic rats. A
      significant decrease in hepatic lipid peroxidation and significant increases in
      hepatic superoxide dismutase, catalase, and glutathione peroxidase were observed
      in the MFGE supplemented group. The results suggest that dietary supplementation
      with MFGEs enriched with CoQs exerts an antidiabetic effect in type 2 diabetic
      rats by improving insulin resistance and hepatic antioxidant enzymes.

PMID- 24866228
TI  - Scientific alchemy and proposed gold standards of care.

PMID- 24866229
TI  - Sporadic spinal hemangioblastomas can be effectively treated by microsurgery
      alone.
AB  - OBJECTIVE: Clinical characteristics and management of hemangioblastomas of the
      spinal cord associated with von Hippel-Lindau syndrome have been extensively
      covered in the literature. This report aims to analyze the characteristics and
      surgical treatment results of sporadic spinal hemangioblastomas (SSHB). METHODS:
      This is a retrospective analysis of 14 patients with SSHB (8 men and 6 women)
      operated on during a span of 23 years. The median age was 41.5 years (24-70
      years). von Hippel Lindau syndrome was excluded by imaging in all patients. The
      median follow-up was 4 years (1-23 years). We also conducted a meta-analysis of
      all 271 SSHB cases reported in the English-speaking language literature from 1967
      to 2011. RESULTS: Nine (64.3%) lesions were cervical, 3 (28.5%) were thoracic,
      and 1 (7.1%) was lumbar. Eight (57.1%) tumors were dorsal intramedullary, 4
      (28.6%) were exophytic, 1 (7.1%) was intradural extramedullary, and 1 (7.1%) was
      completely extradural. Diffuse segmental cord enlargement was present in 7
      patients (50%) and a cyst/syrinx was present in 7 (50%). These 14 patients
      underwent 15 operations, and gross total resection was achieved in all
      operations. There was no mortality. Symptoms improved after 8 (53.3%) of 15
      operations, remained the same after 5 (33.3%), and worsened after 2 (13.3%). The
      mean Karnofsky performance score improved from 79.3 (+/- 17.5) to 87.3 (+/- 12.2)
      after 6 months of follow-up. There was one recurrence 15 years after magnetic
      resonance imaging confirmed total resection. CONCLUSIONS: The SSHBs occur most
      often in the upper spinal cord. Excellent surgical results and long-term outcome
      can be achieved using microsurgery alone with only rare recurrences.

PMID- 24866233
TI  - Conceptualizations of dignity at the end of life: exploring theoretical and
      cultural congruence with dignity therapy.
AB  - AIM: To explore the conceptualization of patients' dignity in the context of end
      of-life care in Taiwan. BACKGROUND: Dignity therapy - a novel nurse-delivered
      psychotherapeutic intervention - has been demonstrated to have potential to
      alleviate terminal patients' psycho-existential distress in western countries. In
      Taiwan, over half of end-of-life patients experience psychological-spiritual
      suffering and dignity therapy might be helpful in improving this situation.
      Hence, a preliminary study to clarify Taiwanese conceptualizations of 'dignity'
      was conducted prior to planning a feasibility study to gauge the potential
      cultural fit of an intervention of this type. DESIGN: Qualitative exploration.
      METHODS: Nine people with terminal cancer and ten health professionals were
      recruited from palliative care services in 2008. In-depth interviews were
      audiotaped and transcribed verbatim. A hermeneutic approach was employed to
      analyse and interpret data. FINDINGS: Being a valuable person is the core meaning
      of patients' dignity and this comprised intrinsic characteristics and extrinsic
      factors. Intrinsic characteristics of dignity encompassed living a moral life,
      having peace of mind and a sense of existence involving the perception of
      resignation to God's will. Extrinsic factors that influenced patients' dignity
      included illness-related distress, care delivery and the perception of being
      loved. A dynamic relationship between these elements determined the state of
      patients' dignity. CONCLUSION: The concept of dignity is culturally bound and
      understood differently in the Chinese and Western context; such differences
      should be considered when planning and delivering care. Modifications should be
      made to dignity therapy to ensure it is culturally congruent with Taiwanese
      patients' beliefs.

PMID- 24866232
TI  - The impact of a novel lung gross dissection protocol on intrapulmonary lymph node
      retrieval from lung cancer resection specimens.
AB  - Although thorough pathologic nodal staging provides the greatest prognostic
      information in patients with potentially curable non-small cell lung cancer, N1
      nodal metastasis is frequently missed. We tested the impact of corrective
      intervention with a novel pathology gross dissection protocol on intrapulmonary
      lymph node retrieval. This study is a retrospective review of consecutive
      lobectomy, or greater, lung resection specimens over a period of 15 months before
      and 15 months after training pathologist's assistants on the novel dissection
      protocol. One hundred forty one specimens were examined before and 121 specimens
      after introduction of the novel dissection protocol. The median number of
      intrapulmonary lymph nodes retrieved increased from 2 to 5 (P<.0001), and the
      75th to 100th percentile range of detected intrapulmonary lymph node metastasis
      increased from 0 to 5 to 0 to 17 (P=.0003). In multivariate analysis, the extent
      of resection, examination period (preintervention or postintervention), and
      pathologic N1 (vs N0) status were most strongly associated with a higher number
      of intrapulmonary lymph nodes examined. A novel pathology dissection protocol is
      a feasible and effective means of improving the retrieval of intrapulmonary lymph
      nodes for examination. Further studies to enhance dissemination and
      implementation of this novel pathology dissection protocol are warranted.

PMID- 24866234
TI  - Involvement of glutamate-cystine/glutamate transporter system in aspirin-induced
      acute gastric mucosa injury.
AB  - Large-dose or long-term use of aspirin tends to cause gastric mucosa injury,
      which is recognized as the major side effect of aspirin. It has been demonstrated
      that glutamate exerts a protective effect on stomach, and the level of glutamate
      is critically controlled by cystine/glutamate transporter (Xc(-)). In the present
      study, we investigated the role of glutamate-cystine/glutamate transporter system
      in aspirin-induced acute gastric mucosa injury in vitro and in vivo. Results
      showed that in human gastric epithelial cells, aspirin incubation increased the
      activity of LDH and the number of apoptotic cells, meanwhile down-regulated the
      mRNA expression of Xc(-) accompanied with decreased glutamate release. Similar
      results were seen in a rat model. In addition, exogenous l-glutamate attenuated
      the gastric mucosa injury and cell damage induced by aspirin both in vitro and in
      vivo. Taken together, our results demonstrated that acute gastric mucosa injury
      induced by aspirin is related to reduction of glutamate-cystine/glutamate
      transporter system activity. 

PMID- 24866235
TI  - Secretory clusterin inhibits osteoclastogenesis by attenuating M-CSF-dependent
      osteoclast precursor cell proliferation.
AB  - Secretory clusterin (sCLU)/apolipoprotein J is a multifunctional glycoprotein
      that is ubiquitously expressed in various tissues. Reduced sCLU in the joints of
      patients with bone erosive disease is associated with disease activity; however,
      its exact role has yet to be elucidated. Here, we report that CLU is expressed
      and secreted during osteoclastogenesis in mouse bone marrow-derived macrophages
      (BMMs) that are treated with receptor activator of nuclear factor kappa-B ligand
      (RANKL) and macrophage colony-stimulating factor (M-CSF). CLU-deficient BMMs
      obtained from CLU(-/-) mice exhibited no significant alterations in OC
      differentiation in comparison with BMMs obtained from wild-type mice. In
      contrast, exogenous sCLU treatment significantly inhibited OC formation in both
      BMMs and OC precursor cultures. The inhibitory effect of sCLU was more prominent
      in BMMs than OC precursor cultures. Interestingly, treating BMMs with sCLU
      decreased the proliferative effects elicited by M-CSF and suppressed M-CSF
      induced ERK activation of OC precursor cells without causing apoptotic cell
      death. This study provides the first evidence that sCLU reduces OC formation by
      inhibiting the actions of M-CSF, thereby suggesting its protective role in bone
      erosion. 

PMID- 24866237
TI  - GGA1 overexpression attenuates amyloidogenic processing of the amyloid precursor
      protein in Niemann-Pick type C cells.
AB  - Alzheimer's disease (AD) and a rare inherited disorder of cholesterol transport,
      Niemann-Pick type C (NPC) share several similarities including aberrant APP
      processing and increased Abeta production. Previously, we have shown that the AD
      like phenotype in NPC model cells involves cholesterol-dependent enhanced APP
      cleavage by beta-secretase and accumulation of both APP and BACE1 within
      endocytic compartments. Since retrograde transport of BACE1 from endocytic
      compartments to the trans-Golgi network (TGN) is regulated by the Golgi-localized
      gamma-ear containing ADP ribosylation factor-binding protein 1 (GGA1), we
      analyzed in this work a potential role of GGA1 in the AD-like phenotype of NPC1
      null cells. Overexpression of GGA1 caused a shift in APP processing towards the
      non-amyloidogenic pathway by increasing the localization of APP at the cell
      surface. However, the observed effect appear to be independent on the subcellular
      localization and phosphorylation state of BACE1. These findings show that the AD
      like phenotype of NPC model cells can be partly reverted by promoting a non
      amyloidogenic processing of APP through the upregulation of GGA1 supporting its
      preventive role against AD. 

PMID- 24866236
TI  - Immunization method for multi-pass membrane proteins using highly metastatic cell
      lines.
AB  - A novel method using metastatic breast cancer cell lines was established for
      producing monoclonal antibodies (mAbs) against multi-span membrane proteins.
      Grafting of metastatic cells (MCF7-14) into the mammary gland of BALB/cJ/nu/nu
      mice induced splenic hypertrophy (1.6-3.0*10(8)cells/spleen [n=6]). More than
      half of the mAbs against MCF7-14 cells reacted with the cell membrane. Inducing
      production of antibodies against the extracellular domain of multi-pass membrane
      proteins is difficult. Because the protein structure becomes more complex as the
      number of transmembrane domains increases, preparing antigens for immunization in
      which the original structure is maintained is challenging. Using highly
      metastatic MDA-MB231 cells as the host cell line, we produced mAbs against a 12
      transmembrane protein, solute carrier family 6 member 6 (SLC6A6), as a model
      antigen. When SLC6A6-overexpressing MDA-MB231 cells were grafted into nude mice,
      the number of splenocytes increased to 2.7-11.4*10(8)cells/spleen (n=10). Seven
      mAb-producing clones that not only recognized the extracellular domain of SLC6A6
      but also were of the IgG subclass were obtained. Immunocytochemistry and flow
      cytometry analyses revealed that these mAbs recognized the native form of the
      extracellular domain of SLC6A6 on the cell surface. Our novel immunization method
      involving highly metastatic cells could be used to develop therapeutic mAbs
      against other multi-pass membrane proteins. 

PMID- 24866238
TI  - MicroRNA-429 induces tumorigenesis of human non-small cell lung cancer cells and
      targets multiple tumor suppressor genes.
AB  - Lung cancer is the major cause of cancer death globally. MicroRNAs are
      evolutionally conserved small noncoding RNAs that are critical for the regulation
      of gene expression. Aberrant expression of microRNA (miRNA) has been implicated
      in cancer initiation and progression. In this study, we demonstrated that the
      expression of miR-429 are often upregulated in non-small cell lung cancer (NSCLC)
      compared with normal lung tissues, and its expression level is also increased in
      NSCLC cell lines compared with normal lung cells. Overexpression of miR-429 in
      A549 NSCLC cells significantly promoted cell proliferation, migration and
      invasion, whereas inhibition of miR-429 inhibits these effects. Furthermore, we
      demonstrated that miR-429 down-regulates PTEN, RASSF8 and TIMP2 expression by
      directly targeting the 3'-untranslated region of these target genes. Taken
      together, our results suggest that miR-429 plays an important role in promoting
      the proliferation and metastasis of NSCLC cells and is a potential target for
      NSCLC therapy. 

PMID- 24866239
TI  - A pyrene based fluorescence approach to study conformation of apolipoprotein E3
      in macrophage-generated nascent high density lipoprotein.
AB  - Apolipoprotein E3 (apoE3) is an anti-atherogenic apolipoprotein with the ability
      to exist in lipid-free and lipoprotein-associated states. During atherosclerosis,
      its function in promoting cholesterol efflux from macrophages via the ATP-binding
      cassette transporter A1 (ABCA1) takes a prominent role, leading to generation of
      nascent high density lipoprotein (nHDL) particles. The objective of this study is
      to understand the conformation adopted by apoE3 in macrophage-generated nHDL
      using a fluorescence spectroscopic approach involving pyrene. Pyrene-labeled
      recombinant human apoE3 displayed a robust ability to stimulate ABCA1-mediated
      cholesterol efflux from cholesterol-loaded J774 macrophages (which do not express
      apoE), comparable to that elicited by unlabeled apoE3. The nHDL recovered from
      the conditioned medium revealed the presence of apoE3 by immunoblot analysis. A
      heterogeneous population of nHDL bearing exogenously added apoE3 was generated
      with particle size varying from ~12 to ~19 nm in diameter, corresponding to
      molecular mass of ~450 to ~700 kDa. The lipid: apoE3 ratio varied from ~60:1 to
      10:1. A significant extent of pyrene excimer emission was noted in nHDL,
      indicative of spatial proximity between Cys112 on neighboring apoE3 molecules
      similar to that noted in reconstituted HDL. Cross-linking analysis using Cys
      specific cross-linkers revealed the predominant presence of dimers. Taken
      together the data indicate a double belt arrangement of apoE molecules on nHDL. A
      similar organization of the C-terminal tail of apoE on nHDL was noted when pyrene
      apoEA277C(201-299) was used as the cholesterol acceptor. These studies open up
      the possibility of using exogenously labeled apoE3 to generate nHDL for
      structural and conformational analysis.

PMID- 24866240
TI  - Non-lysosomal degradation pathway for N-linked glycans and dolichol-linked
      oligosaccharides.
AB  - There is growing evidence that asparagine (N)-linked glycans play pivotal roles
      in protein folding and intra- or intercellular trafficking of N-glycosylated
      proteins. During the N-glycosylation of proteins, significant amounts of free
      oligosaccharides (fOSs) and phosphorylated oligosaccharides (POSs) are generated
      at the endoplasmic reticulum (ER) membrane by unclarified mechanisms. fOSs are
      also formed in the cytosol by the enzymatic deglycosylation of misfolded
      glycoproteins destined for proteasomal degradation. This article summarizes the
      current knowledge of the molecular and regulatory mechanisms underlying the
      formation of fOSs and POSs in mammalian cells and Saccharomyces cerevisiae. 

PMID- 24866241
TI  - Soluble CD40 ligand-activated B cells from patients with chronic hepatitis B
      virus infection as antigen presenting cells to induce hepatitis B virus specific
      cytotoxic T lymphocytes.
AB  - Chronic hepatitis B virus (HBV) infection is the result of an inadequate
      antiviral immune response to the virus. In this study, we aimed to investigate
      whether the soluble CD40 ligand-activated B (CD40-B) cells could present antigen
      and induce specific cytotoxic T lymphocytes (CTLs) in patients with chronic HBV
      infection. We observed that after activated by sCD40L, the expression of CD80,
      CD86, major histocompatibility complex (MHC) I and II molecules on the CD40-B
      cells was significantly increased. Cytometry and fluorescence microscopy showed
      that more than 41.34% CD40-B cells were loaded by the HBcAg peptide. Furthermore,
      after been activated and HBcAg18-27 antigen peptide pulsed, B cells obtained from
      patients with chronic HBV infection could induce HBcAg18-27 specific CTLs in
      vitro. Taken together, our results show that B cells from patients with chronic
      HBV infection can be activated by sCD40L and may function as antigen presenting
      cells and induce HBV-specific CTLs. 

PMID- 24866242
TI  - Interleukin-33/ST2 signaling promotes production of interleukin-6 and interleukin
      8 in systemic inflammation in cigarette smoke-induced chronic obstructive
      pulmonary disease mice.
AB  - Interleukin-33 is a newly described member of the interleukin-1 family. Recent
      research suggests that IL-33 is increased in lungs and plays a critical role in
      chronic airway inflammation in cigarette smoke-induced chronic obstructive
      pulmonary disease (COPD) mice. To determine the role of IL-33 in systemic
      inflammation, we induced COPD mice models by passive cigarette smoking and
      identified the IL-33 expression in bronchial endothelial cells and peripheral
      blood mononuclear cells (PBMCs) of them. After isolation, PBMCs were cultured and
      stimulated in vitro. We measured expressions of interleukin-6 and interleukin-8
      in PBMCs in different groups. The expression of IL-33 in bronchial endothelial
      cells and PBMCs of COPD mice were highly expressed. Stimulated by cigarette smoke
      extract (CSE), the expression of IL-6 and IL-8 were induced and enhanced by IL
      33. PBMCs of COPD mice produced more IL-6 and IL-8 stimulated by CSE and IL-33.
      Expression of IL-6 and IL-8 were decreased when stimulated by IL-33 together with
      soluble ST2. The mRNA production of ST2 in IL-33 stimulated PBMCs was increased.
      Being pretreated with several kinds of MAPK inhibitors, the secretions of IL-6
      and IL-8 in PBMCs did not decrease except for the p38 MAPK inhibitor. We found
      that IL-33 could induce and enhance the expression of IL-6 and IL-8 in PBMCs of
      COPD mice via p38 MAPK pathway, and it is a promoter of the IL-6 and IL-8
      production in systemic inflammation in COPD mice. 

PMID- 24866243
TI  - Smad4 mediated BMP2 signal is essential for the regulation of GATA4 and Nkx2.5 by
      affecting the histone H3 acetylation in H9c2 cells.
AB  - BMP2 signaling pathway plays critical roles during heart development, Smad4
      encodes the only common Smad protein in mammals, which is a pivotal nuclear
      mediator. Our previous studies showed that BMP2 enhanced the expression of
      cardiac transcription factors in part by increasing histone H3 acetylation. In
      the present study, we tested the hypothesis that Smad4 mediated BMP2 signaling
      pathway is essential for the expression of cardiac core transcription factors by
      affecting the histone H3 acetylation. We successfully constructed a lentivirus
      mediated short hairpin RNA interference vector targeting Smad4 (Lv-Smad4) in rat
      H9c2 embryonic cardiac myocytes (H9c2 cells) and demonstrated that it suppressed
      the expression of the Smad4 gene. Cultured H9c2 cells were transfected with
      recombinant adenoviruses expressing human BMP2 (AdBMP2) with or without Lv-Smad4.
      Quantitative real-time RT-PCR analysis showed that knocking down of Smad4
      substantially inhibited both AdBMP2-induced and basal expression levels of
      cardiac transcription factors GATA4 and Nkx2.5, but not MEF2c and Tbx5.
      Similarly, chromatin immunoprecipitation (ChIP) analysis showed that knocking
      down of Smad4 inhibited both AdBMP2-induced and basal histone H3 acetylation
      levels in the promoter regions of GATA4 and Nkx2.5, but not of Tbx5 and MEF2c. In
      addition, Lv-Smad4 selectively suppressed AdBMP2-induced expression of HAT p300,
      but not of HAT GCN5 in H9c2 cells. The data indicated that inhibition of Smad4
      diminished both AdBMP2 induced and basal histone acetylation levels in the
      promoter regions of GATA4 and Nkx2.5, suggesting that Smad4 mediated BMP2
      signaling pathway was essential for the regulation of GATA4 and Nkx2.5 by
      affecting the histone H3 acetylation in H9c2 cells. 

PMID- 24866244
TI  - Cancer-testis antigen HCA587/MAGE-C2 interacts with BS69 and promotes its
      degradation in the ubiquitin-proteasome pathway.
AB  - HCA587, also known as MAGE-C2, belonging to the MAGE gene family which is
      characterized by a conserved MAGE Homology Domain, is active in various types of
      tumors and silent in normal tissues except in male germ-line cells. The
      biological function of HCA587 is largely unknown. To analyze it, we attempted to
      identify protein partners of HCA587. We immunopurified HCA587-containing complex
      from HEK293 cells and identified BS69, a potential tumor suppressor, as an
      associated protein by mass spectrometry, and the following Immunoprecipitation
      and GST pull-down assays confirmed HCA587 interaction with BS69. Interestingly,
      overexpression of HCA587 promoted ubiquitination and the proteasomal degradation
      of BS69 whereas knockdown of endogenous HCA587 increased the protein level of
      BS69. Consistent with a functional role for BS69 in negatively regulating LMP1
      induced NF-kappaB activation, overexpression of HCA587 resulted in a significant
      enhancement of LMP1-induced IL-6 production. These data indicate that HCA587 is a
      new negative regulator of BS69. 

PMID- 24866245
TI  - Dolichol biosynthesis: the occurrence of epoxy dolichol in skipjack tuna liver.
AB  - Polyisoprenoid alcohols from the livers of temperate sea fish (skipjack tuna,
      chub mackerel, red sea bream and rainbow trout) were analyzed by using 2D-TLC,
      electrospray ionization (ESI) mass spectrometry and NMR methods. Dolichols (Dols)
      were detected in all the fish livers, and they were composed of 19-22 isoprene
      units with Dol-20 as the predominant prenolog. In addition, Dol-like family
      compounds were found by using 2D-TLC on skipjack tuna samples. These compounds
      were found to have a larger molecular mass than the Dol family by 16 mass units.
      NMR analysis indicated that the Dol-like compounds were consistent with the
      terminal epoxide structure of Dols (the omega-oxirane derivatives of Dols). ESI
      analysis also revealed the occurrence of dehydro molecules in both Dols and epoxy
      Dols (Dol-like) fractions. The occurrence of epoxy Dols in fish is discussed in
      context with the biosynthesis of Dols, which is responsible for forming Dol
      phosphate, which lead to Dol-PP-oligosaccharide. 

PMID- 24866246
TI  - Intracellular adenosine formation and release by freshly-isolated vascular
      endothelial cells from rat skeletal muscle: effects of hypoxia and/or acidosis.
AB  - Previous studies suggested indirectly that vascular endothelial cells (VECs)
      might be able to release intracellularly-formed adenosine. We isolated VECs from
      the rat soleus muscle using collagenase digestion and magnetic-activated cell
      sorting (MACS). The VEC preparation had >90% purity based on cell morphology,
      fluorescence immunostaining, and RT-PCR of endothelial markers. The kinetic
      properties of endothelial cytosolic 5'-nucleotidase suggested it was the AMP
      preferring N-I isoform: its catalytic activity was 4 times higher than ecto
      5'nucleotidase. Adenosine kinase had 50 times greater catalytic activity than
      adenosine deaminase, suggesting that adenosine removal in VECs is mainly through
      incorporation into adenine nucleotides. The maximal activities of cytosolic 5'
      nucleotidase and adenosine kinase were similar. Adenosine and ATP accumulated in
      the medium surrounding VECs in primary culture. Hypoxia doubled the adenosine,
      but ATP was unchanged; AOPCP did not alter medium adenosine, suggesting that
      hypoxic VECs had released intracellularly-formed adenosine. Acidosis increased
      medium ATP, but extracellular conversion of ATP to AMP was inhibited, and
      adenosine remained unchanged. Acidosis in the buffer-perfused rat gracilis muscle
      elevated AMP and adenosine in the venous effluent, but AOPCP abolished the
      increase in adenosine, suggesting that adenosine is formed extracellularly by non
      endothelial tissues during acidosis in vivo. Hypoxia plus acidosis increased
      medium ATP by a similar amount to acidosis alone and adenosine 6-fold; AOPCP
      returned the medium adenosine to the level seen with hypoxia alone. These data
      suggest that VECs release intracellularly formed adenosine in hypoxia, ATP during
      acidosis, and both under simulated ischaemic conditions, with further
      extracellular conversion of ATP to adenosine. 

PMID- 24866247
TI  - ALS2CR7 (CDK15) attenuates TRAIL induced apoptosis by inducing phosphorylation of
      survivin Thr34.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is considered a
      promising agent for medical applications because it induces apoptosis selectively
      in a variety of cancer cells without toxicity to normal human cells. However, its
      therapeutic potential has been limited by the existence of several cancer cells
      with TRAIL resistance. TRAIL resistance results from a variety of mechanisms,
      which occur at various points in the cellular signaling pathways. In this study,
      we demonstrate that ALS2CR7 (CDK15) can mediate resistance to TRAIL. We also
      demonstrate that cell viability of TRAIL sensitive HCT116 and MDA-MB-231 cells
      increased after TRAIL treatment in ALS2CR7 transfected cancer cells compared with
      vector transfected cancer cells. Furthermore, cell viability was decreased by
      TRAIL treatment after knockdown with ALS2CR7 siRNA in TRAIL resistant HT29 and
      MCF-7 cells. We also show that the activated form of apoptotic proteins such as
      caspase-3, -8 and -9 and PARP increased after TRAIL treatment in the control
      group, but decreased in the ALS2CR7 transfected group. The expression of survival
      proteins such as bcl2 and survivin in TRAIL sensitive cancer cells increased in
      the ALS2CR7 transfected group, but decreased in TRAIL resistant cancer cells
      treated with ALS2CR7 siRNA. Other survival proteins such as FLIP and XIAP were
      not affected. ALS2CR7 appears to bind with only survivin, and not bcl2. The
      phospho-survivin (Thr34) critical in drug resistance was increased by
      transfection with ALS2CR7, but the expression of death receptors such as DR4 and
      DR5 was not affected. ALS2CR7 did not bind with any of the death receptors in our
      study. In summary, our results suggest that ALS2CR7 confers TRAIL resistance to
      cancer cells via phosphorylation of survivin. 

PMID- 24866249
TI  - Molecular clonality and detection of class 1 integron in multidrug-resistant
      Salmonella enterica isolates from animal and human in Iran.
AB  - A total of 70 multidrug-resistant (MDR) Salmonella isolates (44 human and 26
      poultry) were examined. The conserved segment-PCR, restriction fragment length
      polymorphism-PCR analysis, and DNA sequencing were used to determine the presence
      and cassette content of integrons. The genetic relatedness among the isolates was
      examined by pulsed-field gel electrophoresis (PFGE). The rate of integron
      carriage for MDR Salmonella isolates was 91.4% and integron-positive isolates
      belonged to six distinct serovars. Out of 64 integron-positive isolates, only
      four Salmonella Paratyphi C isolates could transfer integrons to Escherichia coli
      K12 by conjugation. Thirty-three PFGE types were detected in 52 integron-positive
      isolates, including 22, 4, 3, 2, 1, and 1 patterns among Salmonella serovars
      Enteritidis, Typhimurium, Paratyphi C, Paratyphi B, Paratyphi A, and Havana,
      respectively. The human and poultry Salmonella Enteritidis isolates from
      different regions with identical integrons had closely related PFGE patterns. Of
      the four integron-positive Salmonella Typhimurium isolates, the two poultry
      isolates with identical integron had very closely related PFGE patterns whereas
      the two human isolates with different integrons showed unrelated PFGE patterns.
      PFGE showed undistinguishable patterns in Salmonella Paratyphi C isolates with
      identical cassettes but revealed relatively unrelated patterns in those with
      different cassettes. Relatively unrelated and identical PFGE patterns were found
      in two Salmonella Paratyphi B and three Salmonella Paratyphi A isolates with the
      same integrons, respectively. In conclusion, PFGE patterns demonstrated more
      genetic relatedness among each Salmonella serovar with identical class 1
      integrons than the same serovar with different class 1 integrons. 

PMID- 24866248
TI  - Seroprevalence of severe fever with thrombocytopenia syndrome virus in
      southeastern China and analysis of risk factors.
AB  - Severe fever with thrombocytopenia syndrome virus (SFTSV) has been prevalent for
      some time in China and it was first identified in 2010. However, the
      seroprevalence of SFTSV in the general population in southeastern China and risk
      factors associated with the infection are currently unclear. Blood samples were
      collected from seven counties across Zhejiang province and tested for the
      presence of SFTSV-specific IgG antibodies by ELISA. A total of 1380 blood samples
      were collected of which 5.51% were seropositive for SFTSV with seroprevalence
      varying significantly between sites. Seroprevalence of SFTSV in people who were
      family members of the patient, lived in the same village as the patient, or lived
      in a different village than the patient varied significantly. There was
      significant difference in seroprevalence between participants who bred domestic
      animals and participants who did not. Domestic animals are probably potential
      reservoir hosts and contact with domestic animals may be a transmission route of
      SFTSV.

PMID- 24866250
TI  - Unilateral renal oncocytosis and combined hybrid tumor: a case report and review
      of the literature.
AB  - Renal oncocytosis is a very rare cause of multiple renal masses. Imaging features
      of renal oncocytosis and combined tumors have rarely been reported. Here, we
      describe a case of unilateral left renal oncocytosis and a combined hybrid tumor
      between chromophobe renal cell carcinoma and oncocytoma, which were depicted on
      CT and MR imaging as multiple enhancing solid masses with one dominant mass.
      Additionally, we reviewed the literature.

PMID- 24866251
TI  - Routine use of dual time 18F-FDG PET for staging of preoperative lung cancer:
      does it affect clinical management?
AB  - OBJECTIVE: The objective of this study was to compare the diagnostic accuracy of
      dual-time-point 18F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography
      (PET) to single-time-point (18)F-FDG PET for staging of preoperative lung cancer.
      METHODS: Between November 2008 and December 2009, 107 patients who were diagnosed
      as having lung cancer or strongly suspected of having lung cancer were enrolled.
      They underwent dual-time-point (18)F-FDG PET following conventional imaging. Dual
      time-point (18)F-FDG PET imaging (whole body) was performed at 1-h (early) post
      FDG injection and repeated (2 h delayed) after injection. The diagnostic accuracy
      of pre-PET staging and post-PET staging was retrospectively evaluated, and the
      diagnostic accuracy of dual-time-point (18)F-FDG PET was compared to that of
      single-time-point (18)F-FDG PET. RESULTS: In 100 patients, the early (18)F-FDG
      PET scan resulted in upstaging of the tumor in ten (10 %) and down-staging of the
      tumor in five (5 %) compared to the conventional scan. The delayed phase of (18)F
      FDG PET provided no additional information on staging for lung cancer patients.
      The remaining seven patients were diagnosed as not having lung cancer.
      CONCLUSION: This study confirmed that dual-time-point (18)F-FDG PET is useful for
      differential diagnosis between benign and malignant lesions, but has no major
      impact on staging and therapeutic management of patients with pathologically
      proven lung cancer.

PMID- 24866252
TI  - A model for internalized stigma in children and adolescents with epilepsy.
AB  - OBJECTIVE: Perceptions of stigma in children and adolescents with epilepsy are
      associated with higher rates of mental health problems. The purpose of this study
      was to test relationships in a model that identified variables most strongly
      associated with perceptions of stigma in children and adolescents with epilepsy.
      Our ultimate goal is to develop a theoretical foundation for future intervention
      research by identifying variables associated with perceptions of stigma that are
      potentially amenable to psychosocial interventions. METHODS: Participants were
      173 children and adolescents with epilepsy who were between 9 and 14 years of
      age. Data were collected in telephone interviews. Stigma was measured using a
      self-report scale. Data were analyzed using structural equation modeling.
      RESULTS: Greater need for information and support, more fear and worry related to
      having epilepsy, greater seizure severity, and younger age were significantly
      associated with greater perceptions of stigma. Female gender, greater need for
      information and support, having at least one seizure in the past year, and lower
      self-efficacy for seizure management were significantly associated with more fear
      and worry related to having epilepsy. CONCLUSIONS: Findings suggest that
      perceptions of stigma are associated with two variables that are amenable to
      psychosocial interventions: fear and worry about having epilepsy and need for
      information and support. Future research should test the efficacy of
      interventions that reduce fear and worry, provide information about epilepsy, and
      reduce need for support.

PMID- 24866253
TI  - Brief narrative exposure therapy for posttraumatic stress in Iraqi refugees: a
      preliminary randomized clinical trial.
AB  - Many Iraqi refugees suffer from posttraumatic stress. Efficient, culturally
      sensitive interventions are needed, and so we adapted narrative exposure therapy
      into a brief version (brief NET) and tested its effects in a sample of
      traumatized Iraqi refugees. Iraqi refugees in the United States reporting
      elevated posttraumatic stress (N = 63) were randomized to brief NET or waitlist
      control conditions in a 2:1 ratio; brief NET was 3 sessions, conducted
      individually, in Arabic. Positive indicators (posttraumatic growth and well
      being) and symptoms (posttraumatic stress, depressive, and somatic) were assessed
      at baseline and 2- and 4-month follow-up. Treatment participation (95.1%
      completion) and study retention (98.4% provided follow-up data) were very high.
      Significant condition by time interactions showed that those receiving brief NET
      had greater posttraumatic growth (d = 0.83) and well-being (d = 0.54) through 4
      months than controls. Brief NET reduced symptoms of posttraumatic stress (d = 
      0.48) and depression (d = -0.46) more, but only at 2 months; symptoms of controls
      also decreased from 2 to 4 months, eliminating condition differences at 4 months.
      Three sessions of brief NET increased growth and well-being and led to symptom
      reduction in highly traumatized Iraqi refugees. This preliminary study suggests
      that brief NET is both acceptable and potentially efficacious in traumatized
      Iraqi refugees. 

PMID- 24866254
TI  - Perioperative blood transfusion does not decrease survival after surgical
      treatment of spinal metastases.
AB  - PURPOSE: To assess whether perioperative allogenic blood transfusions in patients
      undergoing surgical treatment for spinal metastases independently influence
      patient survival. METHODS: A retrospective study including 170 consecutive
      patients undergoing surgical treatment for spinal metastases in 2009 and 2010 at
      a tertiary referral center. Variables related to postoperative survival were all
      included in the same multivariable logistic regression analysis with either 3- or
      12-month survival as the dependent variable. The independent variables were:
      transfusion of allogenic red blood cells, age at surgery, gender, preoperative
      hemoglobin, revised Tokuhashi score and no. of instrumented levels. RESULTS:
      Perioperative allogenic blood transfusion of 1-2 units was associated with
      increased 12-month survival [p = 0.049, odds ratio 2.619 (confidence interval
      1.004-6.831)], but not with 3-month survival. Larger transfusion volumes did not
      significantly influence survival. CONCLUSION: The results of the present study
      support that perioperative blood transfusion of <5 units does not decrease
      survival in patients operated for spinal metastases. Transfusion of 1-2 units
      seems to be associated with increased 12-month survival. Future studies should
      assess if a liberal transfusion regime can be applied to this group of patients;
      thereby, prioritizing early postoperative mobilization.

PMID- 24866256
TI  - Treatment of de novo scoliosis with combined posterior and anterior correction
      and fixation.

PMID- 24866255
TI  - Do X-ray-occult fractures play a role in chronic pain following a whiplash
      injury?
AB  - PURPOSE: Whiplash trauma in motor vehicle accidents (MVA) may involve various
      painful soft tissue damages, but weeks/months later a minority of victims still
      suffers from various long-lasting and disabling symptoms, whiplash-associated
      disorders (WAD). The etiology is currently unknown, but X-ray-occult fractures
      may be one cause in some cases. The purpose of this prospective study was to
      examine the association between occult fractures, as seen on bone single photon
      emission computed tomography (SPECT), with neck-, head- and arm pain. METHODS: An
      inception cohort of 107 patients presenting with acute whiplash symptoms
      following an MVA was invited to have a cervical SPECT shortly post injury and
      again 6 months later. Associations between occult fractures and pain levels at
      baseline, 6 and 12 months of follow-up were analyzed. RESULTS: Eighty-eight
      patients had baseline SPECT performed at median 15 days (range 3-28) post injury,
      but only 49 patients accepted to have the follow-up SPECT at 6 months. Abnormal
      SPECT, defined as minimum one area of focal uptake, was seen in 32 patients at
      baseline, reflecting an occult fracture. Occult fractures were not associated
      with pain levels, neither at baseline nor at follow-up. CONCLUSION: Occult
      fractures do not seem to play a role for development of chronic pain after
      whiplash.

PMID- 24866257
TI  - Missed cervical disc bulges diagnosed with kinematic magnetic resonance imaging.
AB  - PURPOSE: To determine if adding flexion and extension MRI studies to the
      traditional neutral views would be beneficial in the diagnosis of cervical disc
      bulges. METHODS: Five hundred patients underwent MRI in neutral, flexion and
      extension positions. The images were analyzed using computer software to
      objectively quantify the amount of disc bulge. RESULTS: Compared to the neutral
      position, cervical disc bulges were significantly increased in the extension
      position (P < 0.05), but on flexion position, there was no significant difference
      (P > 0.05). For patients without or <3 mm of disc bulge in neutral, 2.97%
      demonstrated an increase in bulge to >=3 mm bulge in flexion, and 16.41%
      demonstrated an increase to >=3 mm bulge in extension. For patients in the
      neutral view that had a baseline disc bulge of 3-5 mm, 3.73% had increased bulges
      to >=5 mm in flexion and 11.57% had increased bulges to >=5 mm in extension.
      CONCLUSION: A significant increase in the degree of cervical disc bulge was found
      by examining extension views when compared with neutral views alone. Kinematic
      MRI views provide valuable added information, especially in situations where
      symptomatic radiculopathy is present without any abnormalities demonstrated on
      traditional neutral MRI.

PMID- 24866258
TI  - Effects of a simple educational intervention in well-baby clinics on women's
      knowledge about and intake of folic acid supplements in the periconceptional
      period: a controlled trial.
AB  - OBJECTIVE: To test the hypothesis that a concise intervention to promote the
      preconception use of folic acid (FA) supplements among mothers who visit a well
      baby clinic (WBC) for the 6-month check-up of their youngest child is effective.
      Effectiveness was measured as intention to use or actual use of FA supplements
      before a next pregnancy among women who expected to be pregnant within 0-12
      months. DESIGN: Controlled intervention study with independent samples of
      intervention and control mothers. The intervention took place at the 6-month
      visit. A post-intervention measurement was done in the intervention group and a
      comparable measurement in the control group at the 11-month check-up visit.
      SETTING: The intervention, verbal and in writing, was implemented in four Dutch
      WBC and given by the WBC physician to the mothers who visited the WBC. SUBJECTS:
      All mothers visiting the WBC were eligible for inclusion, unless they were unable
      to complete a questionnaire. The intervention group consisted of 198 (68 %)
      mothers recruited from 291 6-month intervention visits and the control group of
      215 (84%) mothers recruited from 255 11-month normal visits. RESULTS: In mothers
      who expected to be pregnant within 0-12 months, the proportion using or intending
      to use FA was 65% in the intervention group (n 49) v. 42% in the control group (n
      43; difference 23%, 95% CI 4, 43%, P<0.05). CONCLUSIONS: Health education
      intervention at the 6-month WBC visit is an effective means to promote the use of
      FA supplements or the intention to do so.

PMID- 24866259
TI  - Investigating variations in implementation fidelity of an organizational-level
      occupational health intervention.
AB  - BACKGROUND: The workplace has been suggested as an important arena for health
      promotion, but little is known about how the organizational setting influences
      the implementation of interventions. PURPOSE: The aims of this study are to
      evaluate implementation fidelity in an organizational-level occupational health
      intervention and to investigate possible explanations for variations in fidelity
      between intervention units. METHOD: The intervention consisted of an integration
      of health promotion, occupational health and safety, and a system for continuous
      improvements (Kaizen) and was conducted in a quasi-experimental design at a
      Swedish hospital. Implementation fidelity was evaluated with the Conceptual
      Framework for Implementation Fidelity and implementation factors used to
      investigate variations in fidelity with the Framework for Evaluating
      Organizational-level Interventions. A multi-method approach including interviews,
      Kaizen notes, and questionnaires was applied. RESULTS: Implementation fidelity
      differed between units even though the intervention was introduced and supported
      in the same way. Important differences in all elements proposed in the model for
      evaluating organizational-level interventions, i.e., context, intervention, and
      mental models, were found to explain the differences in fidelity. CONCLUSION:
      Implementation strategies may need to be adapted depending on the local context.
      Implementation fidelity, as well as pre-intervention implementation elements, is
      likely to affect the implementation success and needs to be assessed in
      intervention research. The high variation in fidelity across the units indicates
      the need for adjustments to the type of designs used to assess the effects of
      interventions. Thus, rather than using designs that aim to control variation, it
      may be necessary to use those that aim at exploring and explaining variation,
      such as adapted study designs.

PMID- 24866260
TI  - Novel 1:1 labeling and purification process for C-terminal thioester and single
      cysteine recombinant proteins using generic peptidic toolbox reagents.
AB  - We developed a versatile set of chemical labeling reagents which allow dye
      ligation to the C-terminus of a protein or a single internal cysteine and target
      purification in a simple two-step process. This simple process results in a fully
      1:1 labeled conjugate suitable for all quantitative fluorescence spectroscopy and
      imaging experiments. We refer to a "generic labeling toolbox" because of the
      flexibility to choose one of many available dyes, spacers of different lengths
      and compositions which increase the target solubility, a variety of affinity
      purification tags, and different cleavage chemistries to release the 1:1 labeled
      proteins. Studying protein function in vitro or in the context of live cells and
      organisms is of vital importance in biological research. Although label free
      detection technologies gain increasing interest in molecular recognition science,
      fluorescence spectroscopy is still the most often used detection technique for
      assays and screens both in academic as well as in industrial groups. For
      generations, fluorescence spectroscopists have labeled their proteins of interest
      with small fluorescent dyes by random chemical linking on the proteins' exposed
      lysines and cysteines. Chemical reactions with a certain excess of activated
      esters or maleimides of longer wavelength dyes hardly ever result in quantitative
      labeling of the target protein. Most of the time, more than one exposed amino
      acid side chain reacts. This results in a mixture of dye-protein complexes of
      different labeling stoichiometries and labeling sites. Only mass spectrometry
      allows resolving the precise chemical composition of the conjugates. In
      "classical" ensemble averaging fluorescent experiments, these labeled proteins
      are still useful, and quantification of, e.g., ligand binding experiments, is
      achieved via knowledge of the overall protein concentration and a fluorescent
      signal change which is proportional to the amount of complex formed. With the
      development of fluorescence fluctuation analysis techniques working at single
      molecule resolution, like fluorescence correlation spectroscopy (FCS),
      fluorescence cross correlation spectroscopy (FCCS), fluorescence intensity
      diffusion analysis (FIDA), etc., it became important to work with homogeneously
      labeled target proteins. Each molecule participating in a binding equilibrium
      should be detectable when it freely fluctuates through the confocal focus of a
      microscope. The measured photon burst for each transition contains information
      about the size and the stoichiometry of a protein complex. Therefore, it is
      important to work with reagents that contain an exact number of tracers per
      protein at identical positions. The ideal fluorescent tracer-protein complex
      stoichiometry is 1:1. While genetic tags such as fluorescent proteins (FPs) are
      widely used to detect proteins, FPs have several limitations compared to chemical
      tags. For example, FPs cannot easily compete with organic dyes in the flexibility
      of modification and spectral range; moreover, FPs have disadvantages in
      brightness and photostability and are therefore not ideal for most biochemical
      single molecule studies. We present the synthesis of a series of exemplaric
      toolbox reagents and labeling results on three target proteins which were needed
      for high throughput screening experiments using fluorescence fluctuation analysis
      at single molecule resolution. On one target, Hu-antigen R (HuR), we demonstrated
      the activity of the 1:1 labeled protein in ribonucleic acid (RNA) binding, and
      the ease of resolving the stoichiometry of an RNA-HuR complex using the same dye
      on protein and RNA by Fluorescence Intensity Multiple Distribution Analysis
      (FIMDA) detection. 

PMID- 24866261
TI  - Evidence of remediation-induced alteration of subsurface poly- and perfluoroalkyl
      substance distribution at a former firefighter training area.
AB  - Poly- and perfluoroalkyl substances (PFASs) are a class of fluorinated chemicals
      that are utilized in firefighting and have been reported in groundwater and soil
      at several firefighter training areas. In this study, soil and groundwater
      samples were collected from across a former firefighter training area to examine
      the extent to which remedial activities have altered the composition and spatial
      distribution of PFASs in the subsurface. Log Koc values for perfluoroalkyl acids
      (PFAAs), estimated from analysis of paired samples of groundwater and aquifer
      solids, indicated that solid/water partitioning was not entirely consistent with
      predictions based on laboratory studies. Differential PFAA transport was not
      strongly evident in the subsurface, likely due to remediation-induced conditions.
      When compared to the surface soil spatial distributions, the relative
      concentrations of perfluorooctanesulfonate (PFOS) and PFAA precursors in
      groundwater strongly suggest that remedial activities altered the subsurface PFAS
      distribution, presumably through significant pumping of groundwater and
      transformation of precursors to PFAAs. Additional evidence for transformation of
      PFAA precursors during remediation included elevated ratios of
      perfluorohexanesulfonate (PFHxS) to PFOS in groundwater near oxygen sparging
      wells. 

PMID- 24866263
TI  - A comparison of low and high activity precatalysts: do the calculated energy
      barriers during the self-metathesis reaction of 1-octene correlate with the
      precatalyst metathesis activity?
AB  - The self-metathesis reaction of 1-octene with several well-known Grubbs-type
      precatalysts and the new Z-selective Grubbs precatalyst were studied with
      molecular modeling. The obtained Gibbs-free energy values for all the steps
      during the productive metathesis of 1-octene were compared to the values obtained
      for some low catalytic activity precatalysts. Determining how the Gibbs-free
      energy values of highly active precatalysts compare to that of low catalytic
      activity precatalysts gave a deeper insight into the mechanism. The questionable
      correlation of the theoretically observed trends with those obtained
      experimentally does point to the need to be very cautious when making assumptions
      from theoretical results without a sufficiently large dataset.

PMID- 24866262
TI  - Concurrent validity of accelerations measured using a tri-axial inertial
      measurement unit while walking on firm, compliant and uneven surfaces.
AB  - Although accelerometers are extensively used for assessing gait, limited research
      has evaluated the concurrent validity of these devices on less predictable
      walking surfaces or the comparability of different methods used for gravitational
      acceleration compensation. This study evaluated the concurrent validity of trunk
      accelerations derived from a tri-axial inertial measurement unit while walking on
      firm, compliant and uneven surfaces and contrasted two methods used to remove
      gravitational accelerations; i) subtraction of the best linear fit from the data
      (detrending); and ii) use of orientation information (quaternions) from the
      inertial measurement unit. Twelve older and twelve younger adults walked at their
      preferred speed along firm, compliant and uneven walkways. Accelerations were
      evaluated for the thoracic spine (T12) using a tri-axial inertial measurement
      unit and an eleven-camera Vicon system. The findings demonstrated excellent
      agreement between accelerations derived from the inertial measurement unit and
      motion analysis system, including while walking on uneven surfaces that better
      approximate a real-world setting (all differences <0.16 m.s(-2)). Detrending
      produced slightly better agreement between the inertial measurement unit and
      Vicon system on firm surfaces (delta range: -0.05 to 0.06 vs. 0.00 to 0.14 m.s(
      2)), whereas the quaternion method performed better when walking on compliant and
      uneven walkways (delta range: -0.16 to -0.02 vs. -0.07 to 0.07 m.s(-2)). The
      technique used to compensate for gravitational accelerations requires
      consideration in future research, particularly when walking on compliant and
      uneven surfaces. These findings demonstrate trunk accelerations can be accurately
      measured using a wireless inertial measurement unit and are appropriate for
      research that evaluates healthy populations in complex environments.

PMID- 24866264
TI  - Exposure to bisphenol A among school children in eastern China: a multicenter
      cross-sectional study.
AB  - Bisphenol A (BPA) is one of the highest production and consumption volume
      chemicals in the world. Although exposure of children to BPA has been studied in
      Western countries, little is known about its level in China. In this study, total
      BPA was measured in the morning urine samples of 666 school children aged 9-12
      years from three regions in eastern China in 2012. A rapid and sensitive
      ultraperformance liquid chromatography (UPLC) tandem mass spectrometry (MS/MS)
      method was used for the measurement and urinary concentrations of BPA were
      presented as unadjusted (ng/ml), creatinine-adjusted (MUg/g creatinine) and
      specific gravity (SG)-adjusted (ng/ml) forms. BPA was detected in 98.9% of urine
      samples with their unadjusted concentrations ranging from 0.1 to 326.0 ng/ml
      (LOD=0.06 ng/ml), indicating that the exposure of BPA was common for school
      children living in eastern China. The geometric mean and median of BPA was 1.11
      ng/ml (creatinine-adjusted: 2.32 MUg/g creatinine; SG-adjusted: 1.17 ng/ml) and
      1.00 ng/ml (creatinine-adjusted: 2.22 MUg/g creatinine; SG-adjusted: 1.07 ng/ml),
      respectively. The highest urinary BPA level was found in the age group of 12
      years with GM concentration of 1.55 ng/ml, and it decreased with decreasing age
      (11 years: 1.18 ng/ml; 10 years: 1.05 ng/ml; and 9 years: 0.99 ng/ml), but there
      was a lack of consistency for age associated with BPA levels in three study
      areas. The estimated daily intake of BPA (0.023 MUg/kg bw/day) was much lower
      than the tolerable daily and reference dose of 50 MUg/kg bw/day recommended by
      either the European Food Safety Authority or the US Environment Protection
      Agency. There was no significant difference in urinary BPA concentrations between
      children who were overweight or obese and those with normal weight (P=0.26),
      whereas BPA daily intake was unexpectedly higher among normal-weight children
      (P=0.003). Compared with creatinine correction, the correction method of specific
      gravity is preferred to evaluate BPA exposure for children.

PMID- 24866266
TI  - Assessing residential exposure to urban noise using environmental models: does
      the size of the local living neighborhood matter?
AB  - Environmental epidemiological studies rely on the quantification of the exposure
      level in a surface defined as the subject's exposure area. For residential
      exposure, this area is often the subject's neighborhood. However, the variability
      of the size and nature of the neighborhoods makes comparison of the findings
      across studies difficult. This article examines the impact of the neighborhood's
      definition on environmental noise exposure levels obtained from four commonly
      used sampling techniques: address point, facade, buffers, and official zoning. A
      high-definition noise model, built on a middle-sized French city, has been used
      to estimate LAeq,24 h exposure in the vicinity of 10,825 residential buildings.
      Twelve noise exposure indicators have been used to assess inhabitants' exposure.
      Influence of urban environmental factors was analyzed using multilevel modeling.
      When the sampled area increases, the average exposure increases (+3.9 dB),
      whereas the SD decreases (-1.6 dB) (P<0.01). Most of the indicators differ
      statistically. When comparing indicators from the 50-m and 400-m radius buffers,
      the assigned LAeq,24 h level varies across buildings from -9.4 to +22.3 dB. This
      variation is influenced by urban environmental characteristics (P<0.01). On the
      basis of this study's findings, sampling technique, neighborhood size, and
      environmental composition should be carefully considered in further exposure
      studies. 

PMID- 24866265
TI  - Exploration of the composition and sources of urban fine particulate matter
      associated with same-day cardiovascular health effects in Dearborn, Michigan.
AB  - The objective was to explore associations of chemical components and source
      factors of ambient fine particulate matter (aerodynamic diameter <= 2.5 MUm;
      PM2.5) with cardiovascular (CV) changes following same-day exposure to ambient
      PM2.5. Twenty-five healthy adults living in rural Michigan were exposed to
      ambient air in an urban/industrial community for 4 to 5 h daily for five
      consecutive days. CV health outcomes were measured 1-2 h post exposure.
      Contributing emission sources were identified via positive matrix factorization.
      We examined associations between PM2.5 mass, composition and source factors, and
      same-day changes in CV outcomes using mixed-model analyses. PM2.5 mass (10.8 +/-
      6.8 MUg/m(3)), even at low ambient levels, was significantly associated with
      increased heart rate (HR). Trace elements as well as secondary aerosol,
      diesel/urban dust and iron/steel manufacturing factors potentially explained the
      HR changes. However, trace element analysis demonstrated additional associations
      with other CV responses including changes in blood pressure (BP), arterial
      compliance, autonomic balance and trends toward reductions in endothelial
      function. Two factors were related to BP changes (diesel/urban dust, motor
      vehicle) and trends toward impaired endothelial function (diesel/urban dust).
      This study indicates composition of PM2.5 and its sources may contribute to CV
      health effects independently of PM2.5 mass.

PMID- 24866267
TI  - Allergic contact dermatitis caused by acrylates and methacrylates--a 7-year
      study.
AB  - BACKGROUND: Allergic contact dermatitis (ACD) caused by (meth)acrylates is
      traditionally an occupational disease among dentists, printers, and fibreglass
      workers. With the use of artificial nails, cases have been reported both in nail
      technicians and in users. OBJECTIVES: The aims of this study were to characterize
      ACD caused by (meth)acrylates, identify the responsible allergens, and assess the
      sensitivity of the patch test with 2-hydroxyethyl methacrylate (HEMA) for
      diagnosis. METHODS: An observational and retrospective study (January 2006-April
      2013) was performed, evaluating and correlating epidemiological and clinical
      parameters and positive patch test results with (meth)acrylates. RESULTS: Among
      2263 patch tested patients, 122 underwent aimed testing with an extended
      (meth)acrylate series, and 37 showed positive and relevant reactions. Twenty-five
      cases (67.6%) were occupational. Hand eczema with pulpitis was observed in 32
      patients. Twenty-eight cases were related to artificial nails, 3 were related to
      dental materials, and 2 were industrial workers. Oral lesions associated with
      dental prostheses were observed in 4 patients. Thirty-one patients reacted to
      more than one (meth)acrylate. In our sample, beauty technicians working with
      artificial nails were the most affected group (80% of occupational cases).
      CONCLUSION: HEMA detected 80.6% of our cases, and may be considered a good
      screening allergen. However, to perform an accurate diagnosis, it is safer to use
      a broader series of allergens.

PMID- 24866268
TI  - A metallic room-temperature oxide ion conductor.
AB  - Nanoparticles of Bi3 Ir, obtained from a microwave-assisted polyol process,
      activate molecular oxygen from air at room temperature and reversibly intercalate
      it as oxide ions. The closely related structures of Bi3 Ir and Bi3 IrOx (x<=2)
      were investigated by X-ray diffraction, electron microscopy, and quantum-chemical
      modeling. In the topochemically formed metallic suboxide, the intermetallic
      building units are fully preserved. Time- and temperature-dependent monitoring of
      the oxygen uptake in an oxygen-filled chamber shows that the activation energy
      for oxide diffusion (84 meV) is one order of magnitude smaller than that in any
      known material. Bi3 IrOx is the first metallic oxide ion conductor and also the
      first that operates at room temperature. 

PMID- 24866269
TI  - Structure and function of renal macrophages and dendritic cells from lupus-prone
      mice.
AB  - OBJECTIVE: To characterize renal macrophages and dendritic cells (DCs) in 2
      murine models of lupus nephritis. METHODS: We used a bead-based enrichment step
      followed by cell sorting to isolate populations of interest from young mice and
      nephritic mice. Cell morphology was examined by microscopy. Arginase and nitrite
      production was examined using biochemical assays. The antigen-presenting
      functions of the cells were determined using mixed lymphocyte reactions. Selected
      cytokine, chemokine, and Toll-like receptor (TLR) profiles were examined using
      real-time quantitative polymerase chain reaction. RESULTS: We identified 2
      populations of macrophages and 3 populations of DCs in both of our murine models
      of lupus (NZB/NZW and [NZW * BXSB]F1 mice). F4/80(high) macrophages, which were
      resident in normal kidneys and found to be increased in number during nephritis,
      did not produce either arginase or nitrite upon cytokine stimulation and acquired
      a mixed proinflammatory and antiinflammatory functional phenotype during
      nephritis that resembles the constitutively activated phenotype of gut
      F4/80(high) macrophages. The various cell types differed in their expression of
      chemokine receptors and TLRs, consistent with variability in their renal
      location. Resident renal CD103+ DCs were the best antigen-presenting cells and
      could easily be distinguished from CD11c(high) myeloid DCs that accumulated in
      large numbers during nephritis. CONCLUSION: Our study highlights the
      heterogeneity of the macrophage/DC infiltrate in chronic lupus nephritis and
      provides an initial phenotypic and functional analysis of the different cellular
      components that can now be used to define the role of each cell subset in
      nephritis progression or amelioration. Of note, the dominant macrophage
      population that accumulates during nephritis has an acquired phenotype that is
      neither M1 nor M2 and may reflect failure of resolution of inflammation.

PMID- 24866271
TI  - Comparative percutaneous permeation study using caffeine-loaded microemulsion
      showing low reliability of the frozen/thawed skin models.
AB  - The aim of this study was to explore the transdermal delivery potential of a new
      caffeine-containing microemulsion system. The skin permeability of caffeine (CAF)
      was measured in vitro using skin excised from three different animal species:
      rat, rabbit and pig. As shown, microemulsion containing 20% aqueous phase
      enhanced CAF permeation across fresh rat skin by one order of magnitude
      (Papp=8.2*10(-3) vs. 0.86*10(-3) cm/h; enhancement ratio=9.6). The permeability
      coefficient value, the cumulative permeation amount, and the percent of dose
      permeated after 24 h, decreased with the increase of water content from 60% to
      80% in microemulsions due to the apparent increase in the droplet size.
      Importantly, differences were noted between caffeine transport rates across fresh
      and frozen/thawed pig skin whereas microemulsions delivered caffeine at similar
      rates across rat and rabbit skin, either fresh or frozen/thawed. It has been
      shown that the permeability of caffeine through frozen/thawed pig skin was
      abnormally high and was independent of its vehicle properties, i.e., its
      hydrophilic or lipophilic nature. It has been hypothesized that the reason for
      this abnormality is that porcine stratum corneum has a higher ceramide-to
      cholesterol ratio compared to rat and rabbit skin. This unusual phenomenon
      observed in a non-freshly used porcine skin places a question mark on its
      suitability to in vitro evaluation of transdermal drug delivery systems.

PMID- 24866272
TI  - A TPGS-incorporating nanoemulsion of paclitaxel circumvents drug resistance in
      breast cancer.
AB  - Paclitaxel resistance is usually developed in clinical chemotherapy, which
      remains a major obstacle for successful cancer treatment. Herein, we attempted to
      develop a TPGS incorporating nanoemulsion of paclitaxel (NE-PTX) to circumvent
      the drug resistance in breast cancer. NE-PTX was prepared by a self-assembly
      technique and the physicochemical properties were characterized. The efficacy of
      NE-PTX on overcoming paclitaxel resistance was measured by in vitro and in vivo
      evaluation. The measured results indicated that NE-PTX was nanometer-sized
      droplets with the mean diameter of 24.93+/-3.45 nm. The IC50 value of paclitaxel
      in resistant MCF-7/ADR cells was greatly reduced from 101.45 MUg/mL to 5.39
      MUg/mL, which indicated that the paclitaxel resistance was effectively reduced by
      NE-PTX. The reversal of paclitaxel resistance could mainly ascribe to the
      significant inhibition of P-gp activity and enhancement of anti-cancer activity.
      Moreover, the tumor volume in resistant tumor xenograft model treated with NE-PTX
      was only 10.06% of that of paclitaxel solution group, and the tumor inhibitory
      rate of NE-PTX reached 93.84%, which effectively verified the efficacy of NE-PTX
      on treating paclitaxel resistance. Thereby, NE-PTX could provide an effective
      strategy for circumventing paclitaxel resistance in breast cancer.

PMID- 24866273
TI  - Continuous vs. blocks of physiotherapy for motor development in children with
      cerebral palsy and similar syndromes: A prospective randomized study.
AB  - OBJECTIVE: To determine whether physiotherapy is more effective when applied in
      blocks or continuously in children with cerebral palsy (CP). METHODS: A
      prospective randomized cross-over design study compared the effect of regular
      physiotherapy (baseline) with blocks of physiotherapy alternating with no
      physiotherapy over one year. Thirty-nine institutionalized children with CP and
      clinically similar syndromes (6-16 years old, Gross Motor Function Classification
      Scale II-IV) were included. During the first scholastic year, group A received
      regular physiotherapy, group B blocks of physiotherapy and vice versa in the
      second year. The Gross Motor Function Measure 66 (GMFM-66) was the outcome
      measure. RESULTS: Thirteen children in each group completed the study. GMFM-66
      improved (p < 0.05) over the study period in both groups in total; changes (p <
      0.05) were seen only in dimension D (group B) and E (both groups) during regular
      therapy. CONCLUSION: Physiotherapy may be more effective when provided regularly
      rather than in blocks.

PMID- 24866274
TI  - The incontinence impact questionnaire-7 (IIQ-7) can be applicable to Chinese
      males and females with lower urinary tract symptoms.
AB  - AIM AND OBJECTIVES: The aim of this study was to extend the scope of application
      of the Incontinence Impact Questionnaire-7 (IIQ-7) with the objective of
      assessing the applicability, validity, reliability and sensitivity of the IIQ-7
      in both Chinese males and females with lower urinary tract symptoms (LUTS).
      METHODS: The validity, reliability and sensitivity were assessed in 233 patients
      who were recruited in Hong Kong primary-care settings. The internal construct
      validity was assessed by corrected item-total correlation. The convergent
      validity was assessed using Pearson's correlation test against International
      Prostate Symptom Score (IPSS) quality-of-life question and Short Form 12, version
      2 (SF-12v2). The reliability was assessed by the internal consistency (Cronbach's
      alpha coefficient) and 2-week test-retest reliability (intraclass correlation
      coefficient and paired t test). The sensitivity was determined by performing
      known group comparisons by independent t test. RESULTS: Corrected item-total
      correlations were >=0.4 for all items in males and females. Overall, the IIQ-7
      total score had a stronger correlation with IPSS quality-of-life score than the
      SF-12v2. The IIQ-7 showed good internal consistency (Cronbach's alpha coefficient
      >0.7) and good test-retest reliability (ICC > 0.8, paired t test p value >0.05).
      The IIQ-7 was more sensitive than the SF-12v2 to detect differences among
      patients with different levels of symptom severity. CONCLUSIONS: The IIQ-7
      Chinese version appears to be a valid and reliable measure to assess Cantonese
      speaking males and females with LUTS. The IIQ-7 is more sensitive than generic
      health-related quality-of-life measures to detect differences between groups.

PMID- 24866275
TI  - Parents as the start of the solution: a social marketing approach to
      understanding triggers and barriers to entering a childhood weight management
      service.
AB  - BACKGROUND: Childhood obesity is a sensitive subject and barriers exist with
      respect to accessing weight management programmes. Social marketing insight
      gathering provides an opportunity to understand behaviours and address these
      challenges. This project gained insight into the views of parents/carers on
      triggers and barriers to entering a childhood weight management service. METHODS:
      Participants were identified from the public using marketing recruitment. Four
      focus groups were conducted with parents of school aged children (n = 27) by an
      experienced interviewer. Twenty two mothers, three fathers and two grandmothers
      participated, with half describing their child as overweight. Groups discussed
      health behaviours; attitudes to health messages and weight issues; and
      motivations, benefits and barriers with respect to accessing weight management
      services. Discussions were taped and transcribed. Themes were identified using
      framework analysis of content matrix data analysis. RESULTS: Participants were
      aware of healthy lifestyle messages, although the ability to implement these was
      variable. Triggers to seeking help included bullying, health concerns and
      inability to participate in school activities. Barriers included feeling a lack
      of control, desire to avoid conflict and no proven case that weight was a
      problem. Parents wished to be given information regarding their child's weight by
      a trusted person. The Internet and word of mouth were identified as methods of
      recruitment into a weight management service, with a focus on fitness, fun and
      friendliness and being free-of-charge. CONCLUSIONS: Insight gathering can be used
      to establish parental/carer opinion regarding engaging in childhood weight
      management services. A fun, friendly programme that is free of charge appealed to
      parents. Local community involvement around normalising child weight issues may
      boost referrals into child healthy weight interventions.

PMID- 24866276
TI  - Urinary nerve growth factor correlates with the severity of urgency and pain.
AB  - INTRODUCTION AND HYPOTHESIS: Urinary nerve-growth-factor (NGF) level reflected
      the severity of urgency in patients with lower urinary tract symptoms (LUTS) and
      pain in patients with Bladder pain syndrome/interstitial cystitis (BPS/IC). The
      aim of this study was to investigate the levels of biomarkers, nerve growth
      factor (NGF), and prostaglandin E2 (PGE2) among disease groups sharing similar
      urinary symptoms and to elucidate which symptoms are related to individual
      biomarker levels. METHODS: We studied 83 patients with LUTS who visited our
      outpatient clinic from May 2011 to December 2012. On the basis of clinical
      symptoms and a 3-day voiding diary, patients were classified into three groups:
      those with frequency (n = 13), overactive bladder (OAB) (n = 35), and BPS/IC (n =
      35). Patients with stress urinary incontinence (SUI) or microscopic hematuria
      served as controls (n = 24). Storage symptoms were evaluated based on OAB symptom
      score (OAB-SS). RESULTS: Mean patient age was 62.08 +/- 11.47 (range, 23-84).
      Urinary NGF and creatinine-normalized NGF levels were significantly increased in
      those with OAB (201.90 and 4.08, respectively) and BPS/IC (173.71 and 2.72)
      compared with controls (77.77 and 1.29) and those with frequency (67.76 and
      1.23). Neither value significantly differed between OAB and BPS/IC patients or
      between controls and frequency patients. Urinary PGE2 and creatinine-normalized
      PGE2 levels were not significantly different among groups. On linear regression
      analysis, urinary NGF levels were significantly correlated with urgency severity
      overall (R = 0.222) and also pain in BPS/IC patients (R = 0.409). CONCLUSIONS:
      The levels of urinary NGF were elevated in patients with OAB and BPS/IC but not
      those with frequency and reflected the severity of urgency. In BPS/IC patients,
      urinary NGF increased with pain severity.

PMID- 24866277
TI  - Changes in elastin density in different locations of the vaginal wall in women
      with pelvic organ prolapse.
AB  - INTRODUCTION AND HYPOTHESIS: The purpose of this study was to analyze the
      histomorphometric properties of the vaginal wall in women with pelvic organ
      prolapse (POP). METHODS: In 15 women undergoing surgery for POP, full-thickness
      biopsies were collected at two different sites of location from the anterior
      and/or posterior vaginal wall. Properties of the precervical area (POP-Q point
      C/D) were compared with the most distal portion of the vaginal wall (POP-Q point
      Ba/Bp) using histological staining and immunohistochemistry. The densities of
      total collagen fibers, elastic fibers, smooth muscle cells, and blood vessels
      were determined by combining high-resolution virtual imaging and computer
      assisted digital image analysis. RESULTS: The mean elastin density was
      significantly decreased in the lamina propria and muscularis layer of the vaginal
      wall from the most distal portion of the prolapsed vaginal wall compared with the
      precervical area. This difference was statistically significant in the lamina
      propria for both anterior (8.4 +/- 1.2 and 12.1 +/- 2.0, p = 0.048) and posterior
      (6.8 +/- 0.5 and 10.1 +/- 1.4, p = 0.040) locations, and in the muscularis for
      the anterior (5.2 +/- 0.4 and 8.4 +/- 1.2, p = 0.009) vaginal wall. There were no
      statistically significant differences in the mean densities of collagen fibers,
      smooth muscle cells or blood vessels between the two locations. CONCLUSIONS: In
      this study, we observed changes in elastin density in two different locations of
      the vaginal wall from women with POP. The histomorphometric properties of the
      vaginal wall can be variable from one place to another in the same patient. This
      result supports the existence of most vulnerable locations within the vaginal
      wall and the potential benefit of site-specific prolapse surgery.

PMID- 24866278
TI  - Posterior repair quantification (PR-Q) using key anatomical indicators (KAI):
      preliminary report.
AB  - INTRODUCTION AND HYPOTHESIS: Posterior vaginal compartment repairs (PR) have
      traditionally involved a subjective approach. We aim to quantify such repairs
      using key anatomical indicators (KAI). METHODS: At 50 consecutive PRs: perineal
      gap (PG); posterior vaginal vault descent (PVVD); mid-vaginal laxity (MVL-vault
      undisplaced/displaced); and recto-vaginal fascial laxity (RVFL) were measured.
      The total posterior vaginal length (TPVL) and from POP-Q, TVL, GH, Ap, Bp C, D
      were also measured. Surgical details deemed appropriate to each repair were
      recorded. RESULTS: A mean preoperative PG of 2.5 cm was reduced to 0.0 cm
      postoperatively by excision (100 % cases) with an average increase of 21.6 % in
      total vaginal length over that if the repair was commenced at the hymen. There
      was an average reduction of 25.0 % in the genital hiatus (GH). Mean PVVD was 5.3
      cm overall; 6.4 cm for 31 out of 50 (62 %) undergoing sacrospinous colpopexy; 3.5
      cm for 19 out of 50 (38 %) with no ligamentous vault fixation. An approximate
      "cut-off" for PVVD of 5 cm may assist with the differentiation of cases where
      vault fixation may be desirable. Up to 52 % (1.4/2.7 cm) of preoperative MVL
      displacement was due to vaginal vault descent. The MVL undisplaced (mean 1.3 cm)
      may better guide vaginal mucosal trimming. RVFL averaged just 0.8 cm with 22 out
      of 50 (44 %) RVFL being 0.5 cm or less, and not requiring any RVF plicatory
      sutures. CONCLUSIONS: It is possible to use KAI to assist the planning and
      execution of posterior vaginal compartment surgery. The PG, PVVD, MVL, and RVFL
      can indicate surgical measures in the perineum, vaginal vault, vaginal mucosa,
      and recto-vaginal space respectively.

PMID- 24866279
TI  - Relationship between the Pelvic Organ Prolapse Quantification system (POP-Q), the
      Pelvic Floor Impact Questionnaire (PFIQ-7), and the Pelvic Floor Distress
      Inventory (PFDI-20) before and after anterior vaginal wall prolapse surgery.
AB  - INTRODUCTION AND HYPOTHESIS: The aim of this study was to investigate the degree
      of correlation between the Pelvic Organ Quantification system (POP-Q)
      measurements and symptom questionnaire scores before and after surgery. This was
      a part of a randomized controlled study comparing conventional colporrhaphy with
      mesh repair surgery. METHODS: The correlation between POP-Q measurements and
      Pelvic Floor Impact Questionnaire (PFIQ-7) and Pelvic Floor Distress Inventory
      (PFDI-20) scores was investigated in 164 women 55 years or older scheduled for
      primary anterior vaginal wall prolapse surgery at baseline and the correlation
      between the change in point Ba and scores following surgery. Statistical analyses
      used McNemar's and Wilcoxon signed-rank tests, Spearman's rank-order correlation,
      and multiple linear regression. RESULTS: Surgery significantly improved POP-Q,
      PFIQ-7, and PFDI-20 scores, including subscales. We observed weak correlations
      between POP-Q and PFIQ-7, including subscales (r 0.173-0.324, p < 0.05), and PFDI
      20, including the Pelvic Organ Prolapse Distress Inventory (POPDI) subscale (r
      0.180-0.211, p < 0.05). Regression analysis demonstrated a significant
      relationship between point Ba and PFIQ-7 (p = 0.001) and PFDI-20 (p = 0.04),
      respectively. Furthermore, we observed a significant relationship between the
      change in point Ba (following surgery) and change in scores; point Ba following
      surgery was significantly correlated with symptoms of bulging (r = 0.303, p <
      0.01) and bladder-emptying problems (r = 0.213, p < 0.01). CONCLUSIONS: The weak
      correlation between POP-Q and urogenital symptoms based on questionnaire scores
      suggests that neither scoring system is optimal.

PMID- 24866280
TI  - beta-Elemene inhibits proliferation through crosstalk between glia maturation
      factor beta and extracellular signal-regulated kinase 1/2 and impairs drug
      resistance to temozolomide in glioblastoma cells.
AB  - beta-elemene, a plant-derived drug extracted from Curcuma wenyujin, has
      demonstrated marked antiproliferative effects on glioblastoma, while toxicity
      remains low. However, the underlying molecular mechanisms of the antitumor
      activity of beta-elemene remain to be elucidated. Previously, it was identified
      that the glia maturation factor beta (GMFbeta)/mitogen-activated protein kinase
      kinase (MAPK) 3/6/p38 pathway participates in the antiproliferative activity of
      beta-elemene on glioblastoma. In the present study, in order to illustrate the
      association of GMFbeta and the extracellular signal-regulated kinase 1/2 (ERK1/2)
      pathway, U87 and U251 cells were treated with beta-elemene at various doses and
      for different durations, and the expression of phosphorylated ERK1/2 (p-ERK1/2),
      ERK1/2, B-cell lymphoma 2 (Bcl-2), Bcl2-associated X and survivin was examined by
      western blot analysis. Following treatment with beta-elemene and the ERK1/2
      inhibitor PD98059, U87 cell viability was evaluated using a Cell Counting Kit-8
      (CCK-8) assay, and the expression levels of Bcl-2 and survivin were examined by
      western blot analysis. GMFbeta was then downregulated by RNA interference in beta
      elemene-treated U87 cells, and the effect of this on the expression of ERK1/2 and
      p-ERK1/2 was determined by western blot analysis. Finally, the chemosensitisation
      of U87 cells to temozolomide (TMZ) through beta-elemene was examined using the
      CCK-8 assay. The results demonstrated that beta-elemene inhibited the
      proliferation of U87 glioblastoma cells through the GMFbeta-dependent
      inactivation of the ERK1/2-Bcl-2/survivin pathway. Furthermore, inhibition of
      ERK1/2 by PD98059 enhanced the antitumor effect of beta-elemene and impaired the
      expression levels of Bcl-2 and survivin. beta-elemene also increased the
      sensitivity of U87 glioblastoma cells to the chemotherapeutic TMZ, which was
      synergistically enhanced by PD98059. In conclusion, these results suggested that
      GMFbeta-dependent inactivation of the ERK1/2-Bcl-2/survivin pathway mediated the
      antiproliferative effect of beta-elemene on glioblastoma. Therefore, beta-elemene
      is a promising chemosensitizer or adjuvant therapeutic for TMZ against
      glioblastoma brain tumors. 

PMID- 24866281
TI  - The transformation from grid cells to place cells is robust to noise in the grid
      pattern.
AB  - Spatial navigation in rodents has been attributed to place-selective cells in the
      hippocampus and entorhinal cortex. However, there is currently no consensus on
      the neural mechanisms that generate the place-selective activity in hippocampal
      place cells or entorhinal grid cells. Given the massive input connections from
      the superficial layers of the entorhinal cortex to place cells in the hippocampal
      cornu ammonis (CA) regions, it was initially postulated that grid cells drive the
      spatial responses of place cells. However, recent experiments have found that
      place cell responses are stable even when grid cell responses are severely
      distorted, thus suggesting that place cells cannot receive their spatial
      information chiefly from grid cells. Here, we offer an alternative explanation.
      In a model with linear grid-to-place-cell transformation, the transformation can
      be very robust against noise in the grid patterns depending on the nature of the
      noise. In the two more realistic noise scenarios, the transformation was very
      robust, while it was not in the other two scenarios. Although current
      experimental data suggest that other types of place-selective cells modulate
      place cell responses, our results show that the simple grid-to-place-cell
      transformation alone can account for the origin of place selectivity in the place
      cells.

PMID- 24866283
TI  - Short communication: kidney dysfunction among HIV-infected children in Latin
      America and the Caribbean.
AB  - Renal toxicity is a concern in HIV-infected children receiving antiretrovirals.
      However, the prevalence [1.7%; 95% confidence interval (CI): 1.0-2.6%] and
      incidence of kidney dysfunction (0.17 cases/100 person-years; 95% CI: 0.04-0.30)
      were rare in this multicenter cohort study of 1,032 perinatally HIV-infected
      Latin American and Caribbean children followed from 2002 to 2011.

PMID- 24866282
TI  - CCR6, the sole receptor for the chemokine CCL20, promotes spontaneous intestinal
      tumorigenesis.
AB  - Interactions between the inflammatory chemokine CCL20 and its receptor CCR6 have
      been associated with colorectal cancer growth and metastasis, however, a causal
      role for CCL20 signaling through CCR6 in promoting intestinal carcinogenesis has
      not been demonstrated in vivo. In this study, we aimed to determine the role of
      CCL20-CCR6 interactions in spontaneous intestinal tumorigenesis. CCR6-deficient
      mice were crossed with mice heterozygous for a mutation in the adenomatous
      polyposis coli (APC) gene (APCMIN/+ mice) to generate APCMIN/+ mice with CCR6
      knocked out (CCR6KO-APCMIN/+ mice). CCR6KO-APCMIN/+ mice had diminished
      spontaneous intestinal tumorigenesis. CCR6KO-APCMIN/+ also had normal sized
      spleens as compared to the enlarged spleens found in APCMIN/+ mice. Decreased
      macrophage infiltration into intestinal adenomas and non-tumor epithelium was
      observed in CCR6KO-APCMIN/+ as compared to APCMIN/+ mice. CCL20 signaling through
      CCR6 caused increased production of CCL20 by colorectal cancer cell lines.
      Furthermore, CCL20 had a direct mitogenic effect on colorectal cancer cells.
      Thus, interactions between CCL20 and CCR6 promote intestinal carcinogenesis. Our
      results suggest that the intestinal tumorigenesis driven by CCL20-CCR6
      interactions may be driven by macrophage recruitment into the intestine as well
      as proliferation of neoplastic epithelial cells. This interaction could be
      targeted for the treatment or prevention of malignancy. 

PMID- 24866285
TI  - Mine, yours, no one's: children's understanding of how ownership affects object
      use.
AB  - Two experiments examined children's understanding of how ownership affects object
      use. In Experiment 1, 84 children age 4-6 were asked what a person was allowed to
      do with a human-made object that either belonged to the person or belonged to
      someone else. In Experiment 2, 44 children age 4-5 were asked what a person was
      allowed to do with a natural object that belonged to the person, belonged to
      someone else, or belonged to no one. Children were permitted to provide as many
      responses as they wished. Children's responses reflected an appreciation that
      ownership affects a wide range of object uses, including harmless object use.
      Children's responses also reflected an appreciation that owner's rights should be
      upheld regardless of whether the owner's identity is known, or whether the owner
      is nearby. Moreover, children's responses suggest that they view ownership as
      restricting nonowners from using property, rather than affecting use by entitling
      owners.

PMID- 24866286
TI  - Moral judgment and its relation to second-order theory of mind.
AB  - Recent research indicates that moral judgment and 1st-order theory of mind
      abilities are related. What is not known, however, is how 2nd-order theory of
      mind is related to moral judgment. In the present study, we extended previous
      findings by administering a morally relevant theory of mind task (an accidental
      transgressor) to 4- to 7-year-old Chinese children (N = 79) and analyzing
      connections with 2nd-order theory of mind understanding. Using hierarchical
      multiple regression analyses, we found that above and beyond age, children's 1st
      order theory of mind and 2nd-order theory of mind each significantly and uniquely
      contributed to children's moral evaluations of the intention in the accidental
      transgression. These findings highlight the important roles that 1st- and 2nd
      order theory of mind play in leading children to make appropriate moral judgments
      based on an actor's intention in a social situation.

PMID- 24866287
TI  - Longitudinal transactions between personality and occupational roles: a large and
      heterogeneous study of job beginners, stayers, and changers.
AB  - Social norms are central to theoretical accounts of longitudinal person
      environment transactions. On the one hand, individuals are thought to select
      themselves into social roles that fit their personality. On the other hand, it is
      assumed that individuals' personality is transformed by the socializing pressure
      of norm demands. These 2 transactional directions were investigated in a large
      and heterogeneous 5-year longitudinal subsample of job beginners (n = 640, M age
      = 21.24), job stayers (n = 4,137, M age = 46.63), and job changers (n = 2,854, M
      age = 44.68) from the German Socio-Economic Panel. Role demands were coded by
      both students and labor market experts. To demonstrate transactional effects,
      cross-lagged structural equation models were estimated. Substantial selection
      effects were found for both job beginners and job changers. There was also
      evidence for socialization effects, especially for participants who did not
      change jobs. Depending on the trait and the subsample that was investigated,
      selection effects were sometimes corresponsive with socialization effects.
      Personality role demands were temporally consistent across a 4-year period even
      when individuals changed jobs (heterotypic continuity). This is one of the first
      empirical demonstrations of the transactional processes that lead to the
      formation of social niches.

PMID- 24866288
TI  - Lexical, syntactic, and semantic-geometric factors in the acquisition of motion
      predicates.
AB  - We report a study that explored the mechanisms used in hypothesizing meanings for
      novel motion predicates (verbs and prepositions) cross-linguistically. Motion
      stimuli were presented to English- and Greek-speaking adults and preschoolers
      accompanied by (a) a novel intransitive verb, (b) a novel transitive verb, (c) a
      novel transitive preposition, or (d) no novel predicate. Our study provides
      evidence that both language-specific (lexical) and universal (syntactic and
      semantic-geometric) factors shape the acquisition of motion predicates cross
      linguistically. Lexical biases lead to distinct interpretations (more or less
      manner- vs. path-oriented) for novel intransitive verbs in English and Greek;
      however, syntactic (transitivity) cues overcome lexical biases and lead to
      uniformly path interpretations for novel transitive verbs in both languages.
      Syntactic (transitivity) cues also lead to path interpretations of novel motion
      prepositions. Finally, semantic-geometric constraints lead learners in both
      languages to assume that path interpretations abstract away from visual details
      of the motion path.

PMID- 24866289
TI  - Infant externalizing behavior as a self-organizing construct.
AB  - We evaluated the extent to which the externalizing behavior construct is self
      organizing in the first 2 years of life. Based on dynamic systems theory, we
      hypothesized that changes in physical aggression, defiance, activity level, and
      distress to limitations would each be predicted by earlier manifestations of one
      another. These hypotheses were evaluated via mothers' and fathers' reports of 274
      infants' externalizing behaviors at 8, 15, and 24 months of child age. Eight
      month measures of physical aggression, activity level, and/or distress to
      limitations explained increases in physical aggression, defiance, activity level,
      and distress to limitations from 8 to 15 months. Increases in defiance and
      activity level from 15 to 24 months were predicted by 15-month physical
      aggression and/or distress to limitations. These findings suggest that the
      externalizing behavior construct is formed by dynamic interplay among its
      individual elements, particularly between 8 and 15 months.

PMID- 24866290
TI  - Are schools shortchanging boys or girls? The answer rests on methods and
      assumptions: reply to Card (2014) and Penner (2014).
AB  - Our target article (Robinson-Cimpian, Lubienski, Ganley, & Copur-Gencturk, 2014)
      used nationally representative data to examine the development of gender gaps in
      math achievement. We found that when boys and girls demonstrate equivalent math
      test performance and are perceived by their teachers to be equally well behaved
      and engaged with the material, teachers tend to rate girls as less proficient in
      math than boys (Study 1). Moreover, this underrating of girls' proficiency
      appeared to contribute substantially to a widening gender gap in early elementary
      school (Study 2). In this response, we use the thoughtful comments of Card (2014)
      and Penner (2014) as a springboard for discussing the methodologies and
      assumptions of some of the most recent research using nationally representative
      data to explore gender inequities. In the process, we shed light on how recent
      works using the same data reach different conclusions. We also make
      recommendations regarding the use of such data for understanding the development
      of the gender gap and for designing effective interventions.

PMID- 24866291
TI  - Surface organic monolayers control the hygroscopic growth of submicrometer
      particles at high relative humidity.
AB  - Although many organic molecules commonly found in the atmosphere are known to be
      surface-active in macroscopic aqueous solutions, the impact of surface
      partitioning of organic molecules to a microscopic aqueous droplet interface
      remains unclear. Here we measure the droplet size formed, at a relative humidity
      (~99.9%) just below saturation, on submicrometer particles containing an ammonium
      sulfate core and an organic layer of a model compound of varying thickness. The
      12 model organic compounds are a series of dicarboxylic acids (C3 to C10), cis
      pinonic, oleic, lauric, and myristic acids, which represent a broad range in
      solubility from miscible (malonic acid) to insoluble. The variation in droplet
      size with increasing organic aerosol fraction cannot be explained by assuming the
      organic material is dissolved in the bulk droplet. Instead, the wet droplet
      diameters exhibit a complex and nonlinear dependence on organic aerosol volume
      fraction, leading to hygroscopic growth that is in some cases smaller and in
      others larger than that predicted by bulk solubility alone. For palmitic and
      stearic acid, small droplets at or below the detection limit of the instrument
      are observed, indicating significant kinetic limitations for water uptake, which
      are consistent with mass accommodation coefficients on the order of 10(-4). A
      model based on the two-dimensional van der Waals equation of state is used to
      explain the complex droplet growth with organic aerosol fraction and dry
      diameter. The model suggests that mono- and dicarboxylic acids with limited water
      solubility partition to the droplet surface and reduce surface tension only after
      a two-dimensional condensed monolayer is formed. Two relatively soluble
      compounds, malonic and glutaric acid, also appear to form surface phases, which
      increase hygroscopicity. There is a clear alternation in the threshold for
      droplet growth observed for odd and even carbon number diacids, which is
      explained in the model by differences in the excluded molecular areas of even
      (~40 A(2)/molecule) and odd (~20 A(2)/molecule) diacids. These differences are
      consistent with the odd diacids arranged at the droplet interface in "end-to-end"
      configurations with only one acid group in contact with the aqueous phase, which
      is in contrast to even carbon numbered diacids forming "folded" films with both
      acid groups in contact with the bulk phase. Organic matter produced by the
      ozonolysis of alpha-pinene forms surface films that exhibit similar behavior and
      become thinner with oxidation, allowing for greater water uptake. These results
      reveal a new and complex relationship between the composition of an organic
      aerosol and its hygroscopicity, suggesting that organic surface films might
      strongly influence cloud droplet formation as well as the multiphase chemistry of
      organic aerosols. 

PMID- 24866293
TI  - A wavelet-based method for extracting intermittent discontinuities observed in
      human motor behavior.
AB  - Human motor behavior often shows intermittent discontinuities even when people
      try to follow a continuously moving target. Although most previous studies
      revealed common characteristics of this "motor intermittency" using frequency
      analysis, this technique is not always appropriate because the nature of the
      intermittency is not stationary, i.e., the temporal intervals between the
      discontinuities may vary irregularly. In the present paper, we propose a novel
      method for extracting intermittent discontinuities using a continuous wavelet
      transform (CWT). This method is equivalent to the detection of peak of the jerk
      profile in principle, but it successfully and stably detects discontinuities
      using the amplitude and phase information of the complex wavelet transform. More
      specifically, the singularity point on the time-scale plane plays a key role in
      detecting the discontinuities. Another important feature is that the proposed
      method does not require parameter tuning because it is based on the nature of
      hand movement. In addition, this method does not contain any optimization
      process, which avoids explosive increase in computational cost for long time
      series data. The performance of the proposed method was examined using an
      artificial trajectory composed of several primitive movements, and an actual hand
      trajectory in a continuous target-tracking task. The functional rationale of the
      proposed method is discussed. 

PMID- 24866294
TI  - Is there a universal rule for cellular growth?--Problems in studying and
      interpreting this phenomenon.

PMID- 24866292
TI  - Arsenite-induced changes in hepatic protein abundance in cynomolgus monkeys
      (Macaca fascicularis).
AB  - Arsenic is an environmental pollutant, and its liver toxicity has long been
      recognized. The effect of arsenic on liver protein expression was analyzed using
      a proteomic approach in monkeys. Monkeys were orally administered sodium arsenite
      (SA) for 28 days. As shown by 2D-PAGE in combination with MS, the expression
      levels of 16 proteins were quantitatively changed in SA-treated monkey livers
      compared to control-treated monkey livers. Specifically, the levels of two
      proteins, mortalin and tubulin beta chain, were increased, and 14 were decreased,
      including plastin-3, cystathionine-beta-synthase, selenium-binding protein 1,
      annexin A6, alpha-enolase, phosphoenolpyruvate carboxykinase-M, erlin-2, and
      arginase-1. In view of their functional roles, differential expression of these
      proteins may contribute to arsenic-induced liver toxicity, including cell death
      and carcinogenesis. Among the 16 identified proteins, four were selected for
      validation by Western blot and immunohistochemistry. Additional Western blot
      analyses indicated arsenic-induced dysregulation of oxidative stress related,
      genotoxicity-related, and glucose metabolism related proteins in livers from SA
      treated animals. Many changes in the abundance of toxicity-related proteins were
      also demonstrated in SA-treated human hepatoma cells. These data on the arsenic
      induced regulation of proteins with critical roles may help elucidate the
      specific mechanisms underlying arsenic-induced liver toxicity. 

PMID- 24866300
TI  - [Childhood obesity].

PMID- 24866299
TI  - Regional structural vulnerability of the macula in patients with normal tension
      glaucoma.

PMID- 24866301
TI  - [Promising networks, fruitful inquiry].
AB  - This supplement of the Revista Medica del Instituto Mexicano del Seguro Social
      includes 10 original contributions, and also six current themes, all of them
      related to childhood obesity. It is the result of an institutional program that
      it has been identified as Redes de Investigacion Institucional, and it has been
      promoted and developed by the Coordinacion de Investigacion of the Instituto
      Mexicano del Seguro Social. 

PMID- 24866302
TI  - [Economical costs and consequences of childhood obesity].
AB  - There is some concern because the generations born in the last decades of the
      20th century could have lower longevity than the previous ones as a result of the
      diseases caused by obesity. Mexico has the highest index of prevalence of
      childhood obesity, and it has increased very fast. It is fundamental to generate
      healthcare models focused on obese patients, and oriented to the prevention of
      complications. Implementing preventive actions since childhood must be the
      priority. Health education in childhood obesity will be the only realistic way to
      solve the problem. 

PMID- 24866303
TI  - [Increased height in obese schoolchildren versus healthy weight schoolchildren].
AB  - BACKGROUND: There are few articles that document the association between growth
      and obesity. The objective of this study was to compare height between obese
      schoolchildren and healthy weight schoolchildren. METHODS: Cross-sectional study
      performed in 369 healthy weight schoolchildren and 162 obese schoolchildren of an
      elementary school; 49.4 % were females. Subjects were classified by body mass
      index percentiles in healthy weight (5-84), and obese (> 95), and grouped by
      gender and one-year class intervals. It was used Mann-Whitney U test for
      statistical analysis. RESULTS: In all class intervals, height was higher in obese
      schoolgirls when we compared them with healthy weight schoolgirls; we did not
      identify an increasing or decreasing trend related to age. No height difference
      was observed in 6 and 7 years old obese/healthy weight schoolboys; however, from
      8 to 11 years, height increased progressively in obese schoolchildren with a
      difference of 8.8 cm at the age of 10. CONCLUSIONS: The association of obesity
      with periods of accelerated growth suggests the existence of phenotypic variants
      related to metabolic and hormonal factors. Significant higher height values were
      identified in obese schoolchildren when they were compared with their healthy
      weight peers.

PMID- 24866304
TI  - [Model for predicting childhood obesity from diet and physical activity].
AB  - BACKGROUND: If obesity results from the interaction of variables that involve the
      subject and his environment, the alternatives to face the problem could be very
      diverse. The objective of this study was to seek for the best predictive model of
      childhood obesity from energy ingestion, dietary habits and physical activity.
      METHODS: Case control study of 99 obese and 100 healthy weight children (Center
      for Diseases Control criteria). Energy ingestion was estimated by means of a 24
      hour recall, dietary and physical activity habits by validated questionnaires. A
      logistic regression analysis was made. RESULTS: Variables independently
      associated to obesity were higher energy ingestion; lower frequency in mealtimes;
      having the afternoon lunch outside home; higher frequency of consumption of fat,
      junk food and sweetened beverages; lower time of moderate physical activity at
      school and at home; and increased time for homework and watching TV. The
      variables included in the regression model were energy intake; frequency of
      ingestion of fat, junk foods and sweetened beverages; and physical activity at
      home and at school. CONCLUSION: The diversity of associated variables underlines
      the complexity and multi-causal condition of obesity.

PMID- 24866305
TI  - [Estimation of overweight and obesity in preschoolers according to national and
      international normativity].
AB  - BACKGROUND: Prevalence of overweight and obesity in children under 5 years can be
      affected by type of anthropometric indicator and selected threshold values. We
      assessed variation on estimates according to national and international
      regulations (NOM-031-SSA2-1999, NOM-008-SSA3-2010, GPC-SSA-025-08 and GPC-IMSS
      029-08; WHO-2006, CDC-2000 and IOTF, respectively). METHODS: Cross-sectional
      study in all the daycare centers (100 %) affiliated to Instituto Mexicano del
      Seguro Social-Nuevo Leon during June-December, 2010 (n = 11 141 children).
      Overweight and obesity were defined on the basis of each regulation, and total
      and stratified prevalences by age and sex were estimated. RESULTS: According to
      national regulation, overweight/obesity estimates varied from 12 to 22 %, and to
      international normativity, from 3 to 14 %. The highest prevalence was given by
      NOM-008-SSA3-2010 and GPC-SSA-025-08; and the lowest by WHO-2006. There were no
      differences by sex, but they existed by age; the highest discrepancy occurred in
      the 3.0-3.9 age group with 28 %. CONCLUSION: Health personnel and health policy
      makers should be aware of variation on estimates according to the definition
      employed. We recommend to standardize national regulation for pointing out
      overweight/obesity in preschoolers.

PMID- 24866306
TI  - [Anthropometric measures in urban child population from 6 to 12 years from the
      northwest of Mexico].
AB  - BACKGROUND: The degree of overweight-obesity varies according to the conditions
      of each population and depending on geographical area, race or ethnicity,
      socioeconomic status, and susceptibility of each individual. The aim of this
      study was to determine anthropometric measures in urban child population from 6
      to 12 years of Ciudad Obregon, Sonora. METHODS: We studied 684 schoolchildren
      from 6 to 12 years of age, of both genders in the urban area of Ciudad Obregon,
      Sonora. We measured weight, height, arm circumference (AC), waist, and body mass
      index (BMI). We used descriptive statistics (frequencies, percentages), and to
      compare the growth charts of this study vs. the reference standards (CDC and
      Ramos-Galvan), we employed statistical inference (Student t test). RESULTS: On
      average, weight, height, AC, BMI for age by gender were higher than the reference
      standards at all ages. Seventy-four boys (22 %) and 51 girls (14.5 %) were above
      95th percentile. With regards to size, 42 children (12.6 %) were below the 5th
      percentile and 37 (10.5 %) above the 95th percentile. CONCLUSION: Schoolchildren
      in the southern zone of Sonora showed a higher anthropometric pattern than the
      reference standards.

PMID- 24866307
TI  - [Prevalence of overweight and obesity in children from Monterrey, Nuevo Leon].
AB  - BACKGROUND: Pediatric obesity is a major health problem around the globe. It has
      increased in the last decades up to 30 % (in 2010). The aim of this study was to
      establish the prevalence of overweight and obesity in children from zero to 14
      years from three family medicine units and one school. METHODS: A prospective
      study of prevalence, which included children of both sexes who assisted to three
      family medicine units and a junior high school. We assessed the somatometry and
      compared it in accordance to the World Health Organization 2006-2007 references
      and standards. RESULTS: The overall overweight and obesity prevalence in 1624
      children was 45.5 % (15.5 % of overweight and 29.9 % of obesity, respectively). A
      total of 354 of 840 women (42.1 %) and 385 of 784 men (49 %) had overweight and
      obesity (p < 0.05). In both sexes, we did not observed a difference in overweight
      (15.7, women; 15.4, men). However, with regards to obesity, women showed 26.4
      versus 33.6 of men (p < 0.05). We observed only one family unit with major
      obesity prevalence, which probably had an initial overestimation. CONCLUSIONS: We
      found one of the highest prevalences of overweight and obesity in children at a
      national level: up to 45 % in a state of Mexican northwestern. Obesity doubled
      overweight, and it was almost 10 % higher in men than in women.

PMID- 24866308
TI  - [Characterization of obese children with and without metabolic syndrome in a
      pediatric hospital].
AB  - BACKGROUND: The alterations caused by metabolic syndrome (MS) arise progressively
      throughout the years, but they can start at a pediatric age. The objective of
      this paper was to evaluate the biochemical and clinical characteristics of obese
      children with or without MS. METHODS: Descriptive cross-sectional study, in which
      we analyzed, according to the 2010 classification of the Centers for Disease
      Control and Prevention (CDC), 103 obese children between 10 and 15 years from an
      endocrinology service. The variables were weight, size, body mass index (BMI),
      waist circumference (WC), glucose, HDL cholesterol, triglycerides, blood
      pressure, insulin, and HOMA. Means were compared statistically with Student's t
      test, and Mann-Whitney U. RESULTS: Of 103 patients, 55 showed criteria for MS
      (53.3 %) and 48 incomplete criteria for MS (46.6 %). In the group without MS,
      60.4 and 64.5 % showed insulin resistance and hyperinsulinemia, respectively. In
      all the group, 28.1 % showed arterial hypertension, and 23.3 % prehypertension.
      With regards to the means of other parameters that does not belong to the MS, we
      obtained weight (p = 0.008), BMI (p = 0.009), insulin (p = 0.027) and HOMA (p =
      0.023). More than 60 % showed pre-diabetes and almost 50 % blood pressure
      alterations. CONCLUSION: It is urgent to perform a screening in obese children,
      as well as an awareness campaign in mass media, in order to spread the gravity of
      the problem and trigger the search of medical help, and of health professionals
      to establish their diagnosis.

PMID- 24866309
TI  - [Cardiovascular risk in children from 6 to 15 years with exogenous obesity].
AB  - BACKGROUND: The cardiovascular risk (CVR) is increasing and it is related to life
      style and dietary habits; one of the age groups at risk of developing this
      disease are the obese children. The objective of this study was to assess the CVR
      in the obese pediatric population in a secondary care unit of the Instituto
      Mexicano del Seguro Social in San Luis Potosi, Mexico. METHODS: A cross-sectional
      study, in which we used Alustiza's scale to measure CVR. We included the total of
      cases of pediatric obese population in a year. We performed the analysis by each
      of the variables included in the scale (age, sex, body mass index, family history
      of diabetes and obesity, alcohol, blood pressure, cholesterol). High CVR was
      correlated to HDL and glucose, through a statistical analysis with chi-squared.
      RESULTS: We reviewed a total of 100 medical records of children from 6 to 15
      years (52 girls, 48 boys). CVR was low in 26 %, moderate in 14 % and higher in 60
      %. A positive history of obesity was found in 26 %; obesity plus diabetes, 16 %;
      obesity and dyslipidemia, 13 %; hypertension, 11 %. None of the children
      practiced excercise. We found hypercholesterolemia in 46 %, and hyperglycemia in
      34 %. By using chi-squared we found that all variables were statistically
      significant (p < 0.05). CONCLUSIONS: Validated scales are useful to measure CVR
      in children, in order to take action in a timely fashion and avoid the
      persistence of risk in adulthood.

PMID- 24866310
TI  - [Depression and state of nutrition in schoolchildren from Sonora].
AB  - BACKGROUND: Pediatric obesity has become a problem of epidemic proportions, due
      to the inadequate and excessive consumption of food, sedentary lifestyle, and the
      restricted socio-economic development. This causes a major risk in health
      complications that have an effect on the psychological and social spheres of the
      child, which makes him endure such diseases as depression and anxiety. The aim of
      this study was to determine the association between depression and the
      nutritional status of schoolchildren from a family medicine unit in Sonora.
      METHODS: Cross-sectional study performed during 2011 in 101 schoolchildren from
      Sonora. Kovacs test was applied to detect depressive symptoms; nutritional status
      was determined by weight and height; body mass index was calculated according to
      the Center for Disease Control and Prevention (CDC) percentiles. The results were
      analyzed in SPSS version 18 using Mann-Whitney U and chi-square. RESULTS: Of all
      the patients with depression, 19 were obese; the other 10 showed a normal
      nutrition status. Patients with low weight did not show depression. The odds
      ratio (OR) for depression in students with obesity was 3.16, 95 % CI = 1.13,
      7.12. CONCLUSIONS: The detection and management of depression should be
      considered in the treatment of obesity.

PMID- 24866311
TI  - [Cognitive behavioral treatment in the integral management of obesity in
      adolescents].
AB  - OBJECTIVE: Obesity in children and adolescents is associated to a morbidity that
      has increased significantly. It has become a public health problem around the
      world. The objective of this paper was to evaluate the efficacy of the cognitive
      behavioral treatment strategy in the comprehensive management of obesity in
      adolescents. METHODS: Double blind, randomized, and controlled intervention
      study, of four months of follow-up, with a total of 115 obese adolescents, aged
      12 to 16 years. The intervention group received cognitive behavioral treatment
      strategy, as well as advise on diet and exercise. At the same time, the control
      group only received advise on diet and exercise. RESULTS: The percentage of
      adolescents who showed adherence to diet was 73.7 % versus 41.4 %, (p = 0.0009)
      and to exercise, 61.4 % versus 19.0 %, (p < 0.0005); compared with the control
      group, the intervention group was significantly higher. A total of 10 adolescents
      (17.5 %) in the intervention group and 26 (44.8 %) in the control group dropped
      out (p = 0.003). Despite there were significant differences between groups,
      adolescents in the intervention group exhibited a higher and sustained decrease
      in body weight, body mass index, as well as in the body fat percentage.
      CONCLUSIONS: The cognitive behavioral treatment strategy improves adherence and
      decreases desertion of the weight reduction program in adolescents.

PMID- 24866312
TI  - [Family intervention for the management of overweight and obesity in
      schoolchildren].
AB  - BACKGROUND: The management of obesity is complex and it must be
      multidisciplinary. Behavioral treatments for control of childhood obesity are
      based on family; these have a high degree of efficiency. It has been argued that
      when children and their parents are the main goal of the changes of behavior as a
      group, results of weight loss generally are better. The objective of this study
      was to establish the effect of an intervention based on family to reduce weight
      in students with overweight or obesity. METHODS: Quasi-experimental study in
      schoolchildren from 6 to 12 years of age, from a family medicine unit in Ciudad
      Obregon, Sonora, Mexico. The intervention group corresponded to 30 schoolchildren
      with overweight or obesity, and one or both of their parents with overweight or
      obesity; the control group included 30 schoolchildren with overweight or obesity,
      and normal-weight parents. Weight, height and body mass index (BMI) were measured
      at baseline, monthly, and at the end of the study. Student t test was used to
      contrast quantitative variables using the SPSS v.15 program. RESULTS: There were
      differences in weight, but not in BMI, probably due to the effect of size.
      Compared with the control group, a higher proportion of schoolchildren showed an
      improvement with regard to nutritional status. CONCLUSIONS: The family
      intervention is basic for the treatment of overweight and obesity in
      schoolchildren.

PMID- 24866313
TI  - [Genetics of pediatric obesity].
AB  - Obesity is a major health problem around the globe. The statistics of overweight
      and obesity at early ages have reached alarming levels and placed our country in
      the first place in regard to childhood obesity. In the development of obesity two
      major factors take part, one genetic and the other one environmental. From the
      perspective of environmental changes both overweight and obesity result from the
      imbalance in the energy balance: people ingest more energy than they expend.
      Despite people live in the same obesogenic environment not all of them develop
      obesity; it requires genetic factors for this to happen. This review focuses on
      the description of the main methodologies to find genetic markers, as well as the
      main loci in candidate genes, whose single nucleotide polymorphisms (SNPs) are
      associated with obesity and its comorbidities in children, highlighting the
      association of these genes in the Mexican population. Knowledge of the genetic
      markers associated with obesity will help to understand the molecular and
      physiological mechanisms, the genetic background and changes in body mass index
      in the Mexican population. This information is useful for the planning of new
      hypotheses in the search for new biomarkers that can be used in a predictive and
      preventive way, as well as for the development of new therapeutic strategies. 

PMID- 24866314
TI  - [Epigenetics of childhood obesity and diabetes].
AB  - Obesity and type 2 diabetes mellitus (T2DM) result from sedentary lifestyle, high
      carbohydrate diets and genetic predisposition. Epigenetics is a form of genetic
      regulation in specialized cells that does not involve changes in the
      deoxyribonucleic acid (DNA) sequence, but it can be inherited to one or more
      generations through mitosis or meiosis. Children whose mothers develop
      gestational diabetes are more likely to become obese and diabetic in adult life.
      DNA methylation is a major mechanism in the regulation of transcription and gene
      expression of several genes. High levels of glucose and insulin during pregnancy
      modify the risk of developing T2DM, suggesting that the expression pattern is
      modified due to cell memory in a specific tissue. If T2DM is linked to adaptation
      in utero, the obvious primary prevention is to protect the fetal development.
      Future epidemiological studies need to employ more accurate indicators or markers
      of development to show the relationship between a specific disease and the
      exposure to environmental factors. The mechanisms by which malnutrition, and
      intrauterine growth retardation produce changes in the metabolism of glucose and
      insuline are worth to explore in order to control obesity and T2DM. 

PMID- 24866315
TI  - [Psychological, social and cultural factors of overweight and obesity in children
      and adolescents in Mexico].
AB  - Child obesity is a serious problem of public health in Mexico. If we don't
      reverse it quickly, it will generate unsustainable economical consequences to the
      health institutions in this country, as well as serious health problems. This
      article reviews some psychological, social and cultural factors in the health
      illness process, in particular in relation to food choices, the function of the
      family, and the food-related parental practices, changes in physical activity,
      and the role of media. As a conclusion, we can say it is very important to take
      into account psychological and cultural aspects, as well as the family as a whole
      in the creation of public policies in the fight against the obesity epidemic.
      Other fundamental aspect to bear in mind is the generation and effective
      monitoring of regulations on food advertising, particularly that aimed to
      children, and also in regards to a labelling of edible products accessible to all
      people. An interdisciplinary work is essential to generate synergies that help us
      to control obesity in the first place, and then to be able to reverse this
      problem, without disregarding the role of prevention. 

PMID- 24866316
TI  - [Childhood obesity and dyslipidemia].
AB  - Screening and treatment of plasma lipid abnormalities secondary to obesity are
      among the interventions that should be implemented in children who are overweight
      or obese, in order to prevent a cardiovascular event. Dyslipidemias are a group
      of asymptomatic diseases that are commonly caused by abnormal levels of
      lipoproteins in blood; they are a comorbidity that is commonly related to
      obesity, without considering the age of the patient. Among dyslipidemias,
      hypertriglyceridemia has the highest prevalence. The etiology of the dyslipidemia
      should be identified; it allows the proper selection of therapy for the patients
      and their family. The goal is the prevention of cardiovascular complications.
      Reduced caloric intake and a structured physical activity plan should be
      considered for initial treatment for all the overweight and obese patients. For
      adherence to treatment to be successful, the participation of the primary care
      physician and a multidisciplinary team is required. With treatment, the risks and
      complications can be reduced. The participation of a specialist in handling the
      pediatric obese patient with dyslipidemia should be limited to severe cases or
      those at risk for having pancreatitis. 

PMID- 24866317
TI  - [Nonalcoholic fatty liver disease in children].
AB  - Nonalcoholic fatty liver disease (NAFLD) is currently the most common cause of
      liver disease in children and adolescents in the United States of America (USA)
      and probably in the entire western hemisphere, due to the increase in the
      prevalence of overweight and obesity. Steatosis can progress to inflammation,
      fibrosis and even cirrhosis, which increases the morbidity and mortality
      associated to liver disease. In every overweight and obese child a thorough
      analysis should be performed including liver function tests and liver ultrasound,
      in order to establish a timely diagnosis. The liver biopsy is the most specific
      study to rule out other potentially treatable entities. It is necessary to count
      on non-invasive methods to detect children with NAFLD and identify those in risk
      of progression. Biomarkers related to inflammation, oxidative stress, apoptosis
      and fibrosis have been reported. The main goal of the treatment is to modify the
      life style, starting with a healthy diet and an increase of physical activity.
      Regarding pharmacological treatment, there is evidence of histological
      improvement with vitamin E use, as opposed to metformin, but more conclusive
      studies regarding this subject are needed. 

PMID- 24866318
TI  - [Focus of childhood obesity from pediatrics].
AB  - The prevalences of overweight and obesity have increased dramatically in the last
      two decades in the adult and children population. The Organization for
      Cooperation and Economic Development reported in 2010 that Mexico ranks first
      worldwide in childhood obesity. The 2006 National Health and Nutrition Survey
      reported that one of every three teenagers are overweight and obese. In the last
      decades, pediatric hospitals in different parts of the world reported the
      prevalence of secondary malnutrition, since in those days overweight and obesity
      did not represent health problems. Currently, the prevalence of overweight and
      obesity has been scarcely studied in pediatric hospitals. In the Hospital de
      Pediatria (Children's Hospital) of the Instituto Mexicano del Seguro Social's
      Centro Medico Nacional de Occidente it is reported a prevalence of overweight of
      15.4 % and obesity of 12.2 %, which reflects a nutritional transition.Due to the
      high prevalence of overweight and obesity in this pediatric hospital of
      reference, one could conclude that the pediatrician should be able to make a
      correct evaluation of the nutritional state, because, if he does not detect these
      problems, we will be condemning children to suffer from a chronic disease for the
      rest of their lives, and with all the implications in the short, medium and long
      term. 

PMID- 24866319
TI  - Detecting a weak association by testing its multiple perturbations: a data mining
      approach.
AB  - Many risk factors/interventions in epidemiologic/biomedical studies are of
      minuscule effects. To detect such weak associations, one needs a study with a
      very large sample size (the number of subjects, n). The n of a study can be
      increased but unfortunately only to an extent. Here, we propose a novel method
      which hinges on increasing sample size in a different direction-the total number
      of variables (p). We construct a p-based 'multiple perturbation test', and
      conduct power calculations and computer simulations to show that it can achieve a
      very high power to detect weak associations when p can be made very large. As a
      demonstration, we apply the method to analyze a genome-wide association study on
      age-related macular degeneration and identify two novel genetic variants that are
      significantly associated with the disease. The p-based method may set a stage for
      a new paradigm of statistical tests. 

PMID- 24866320
TI  - A systematic review and meta-analysis of the i-gel(r) vs laryngeal mask airway in
      children.
AB  - We systematically reviewed randomised controlled trials of the i-gel(r) vs
      different types of laryngeal mask airway in children. We included nine studies.
      There was no evidence for differences in: rate of insertion at first attempt;
      insertion time; ease of insertion; or gastric tube insertion. The mean (95% CI)
      oropharyngeal leak pressure was 3.29 (2.25-4.34) cmH2 O higher with the i-gel, p
      < 0.00001. The relative rate (95% CI) of a good fibreoptic view through the i-gel
      was 1.10 (1.01-1.19), p = 0.02. There were no significant differences in the
      rates of complications, except for blood on the airway, relative rate with the i
      gel 0.46 (0.23-0.91), p = 0.02. We concluded that the clinical performance of the
      i-gel and LMA was similar, except for three outcomes that favoured the i-gel.

PMID- 24866322
TI  - Smart windows for building integration: a new architecture for photovoltachromic
      devices.
AB  - A new architecture for multifunctional photoelectrochemical devices, namely
      photovoltachromic devices, is disclosed here, capable of producing electric
      energy by solar conversion also modulating the devices' optical transmittance in
      a smart and aesthetically sounding fashion. These devices generally consist of a
      titanium dioxide photoelectrode and of a bifunctional patterned counter electrode
      made of platinum and amorphous tungsten oxide. The innovative configuration
      described hereafter proposes to split the single patterned counter electrode into
      two distinct electrodes, physically overlapped: the central one is suitably
      drilled in order to allow the electrolyte to fill both communicating chambers.
      These three electrode devices allow three independent operating modes:
      photovoltaic, photoelectrochromic, and photovoltachromic. In this paper, we
      report the optical, electrical, and electrochemical characterization of this
      innovative device, varying both available catalytic surface area and the type of
      sensitizing dye. We eventually obtained the following conversion efficiencies,
      2.75%, 2.35%, and 1.91%, in samples having different catalytic areas (397, 360,
      and 320 mm(2), respectively). We inferred that the higher the platinum area on
      the interposed platinum-poly(ethylene naphthalate)-indium tin oxide counter
      electrode, the higher the photovoltaic conversion efficiency. On the other hand,
      a decrease of the intercommunication openings generates a slowdown of bleaching
      processes. 

PMID- 24866321
TI  - Gene expression analysis of laminin-1-induced neurite outgrowth in human
      mesenchymal stem cells derived from bone marrow.
AB  - The mechanisms underlying the differentiation of Mesenchymal stem cells (MSCs)
      toward neuronal cell type are not clearly understood. Earlier, we reported that
      laminin-1 induces neurite outgrowth in human MSCs via c-Jun/AP-1 activation
      through ERK, JNK, and Akt pathways. In this study, we demonstrate that laminin-1
      increases the expression of proneural gene, neuroD1 and induces the expression of
      immediate-early biomarkers of neuronal cell-programming-Egr1, Egr3, PC3, and PC4.
      Gene expression profiling of MSCs cultured on laminin-1 and Poly-l-lysine for 12
      h revealed differential regulation of 267 genes (>1.5 fold, p < 0.05),
      predominantly in the category of nervous system development and affected the
      pathways involved in TGF-beta/TNF-alpha signaling, regulation of MAPK and JNK
      cascade. Data for 11 selected genes related to nervous system development was
      validated by real time PCR. Transcriptional regulatory network analysis revealed
      c-Jun as the key transcription factor regulating majority of differentially
      expressed genes and identified Disrupted in schizophrenia 1, as a novel target of
      c-Jun. Modeling and analysis of biological network showed selective induction of
      Growth Arrest and DNA damage 45 (GADD45B) and repression of NF-kappaB inhibitor A
      (NFkappaBIA). Collectively, our findings provide the basis for understanding the
      molecular mechanisms associated with laminin-1-induced neurogenic expression in
      MSCs.

PMID- 24866323
TI  - Thiolated human serum albumin cross-linked dextran hydrogels as a macroscale
      delivery system.
AB  - Hydrogels play an important role in macroscale delivery systems by enabling the
      transport of cells and molecules. Here we present a facile and benign method to
      prepare a dextran-based hydrogel (Dex-sHSA) using human serum albumin (HSA) as a
      simultaneous drug carrier and covalent cross-linker. Drug binding affinity of the
      albumin protein was conserved in the thiolation step using 2-iminothiolane and
      subsequently, in the in situ gelation step. Oscillation rheometry studies
      confirmed the formation of a three-dimensional viscoelastic network upon reaction
      of dextran and the HSA protein. The mechanical properties of Dex-sHSA hydrogel
      can be tuned by the protein concentration, and the degree of thiolation of sHSA.
      Sustained release of hydrophobic drugs, such as ibuprofen, paclitaxel and
      dexamethasone, from the Dex-sHSA network was shown over one week. Hence, this
      albumin-based dextran hydrogel system demonstrates its potential as a macroscale
      delivery system of hydrophobic therapeutics for a wide range of biomedical
      applications. 

PMID- 24866324
TI  - The role of foot self-care behavior on developing foot ulcers in diabetic
      patients with peripheral neuropathy: a prospective study.
AB  - BACKGROUND: Although foot self-care behavior is viewed as beneficial for the
      prevention of diabetic foot ulceration, the effect of foot self-care behavior on
      the development of diabetic foot ulcer has received little empirical
      investigation. OBJECTIVE: To explore the relationship between foot self-care
      practice and the development of diabetic foot ulcers among diabetic neuropathy
      patients in northern Taiwan. METHODS: A longitudinal study was conducted at one
      medical center and one teaching hospital in northern Taiwan. PARTICIPANTS: A
      total of 295 diabetic patients who lacked sensitivity to a monofilament were
      recruited. Five subjects did not provide follow-up data; thus, only the data of
      290 subjects were analyzed. The mean age was 67.0 years, and 72.1% had six or
      fewer years of education. METHODS: Data were collected by a modified version of
      the physical assessment portion of the Michigan Neuropathy Screening Instrument
      and the Diabetes Foot Self-Care Behavior Scale. Cox regression was used to
      analyze the predictive power of foot self-care behaviors. RESULTS: A total of
      29.3% (n=85) of diabetic neuropathy patients developed a diabetic foot ulcer by
      the one-year follow-up. The total score on the Diabetes Foot Self-Care Behavior
      Scale was significantly associated with the risk of developing foot ulcers
      (HR=1.04, 95% CI=1.01-1.07, p=0.004). After controlling for the demographic
      variables and the number of diabetic foot ulcer hospitalizations, however, the
      effect was non-significant (HR=1.03, 95% CI=1.00-1.06, p=0.061). Among the foot
      self-care behaviors, lotion-applying behavior was the only variable that
      significantly predicted the occurrence of diabetic foot ulcer, even after
      controlling for demographic variables and diabetic foot ulcer predictors
      (neuropathy severity, number of diabetic foot ulcer hospitalizations, insulin
      treatment, and peripheral vascular disease; HR=1.19, 95% CI=1.04-1.36, p=0.012).
      CONCLUSIONS: Among patients with diabetic neuropathy, foot self-care practice may
      be insufficient to prevent the occurrence of diabetic foot ulcer. Instead, lotion
      applying behavior predicted the occurrence of diabetic foot ulcers in diabetic
      patients with neuropathy. Further studies are needed to explore the mechanism of
      lotion-applying behavior as it relates to the occurrence of diabetic foot ulcer.

PMID- 24866326
TI  - Naturally occurring angiotensin I-converting enzyme inhibitory peptide from a
      fertilized egg and its inhibitory mechanism.
AB  - This study was performed to investigate the angiotensin I-converting enzyme (ACE)
      inhibitory activity of peptides derived from fertilized eggs and elucidate the
      inhibition mechanism of these peptides. During incubation, ACE inhibitory
      activity of the peptides remained stable before day 12 and then increased
      markedly on day 15. Two ACE inhibitory peptides, VGVIKAVDKKAGGAGKVT and
      HLFGPPGKKDPV, were purified from peptides on day 15 by consecutive
      chromatography. Because HLFGPPGKKDPV possessed a higher ACE inhibitory activity
      (IC50 = 125 MUM), an antihypertensive effect of this peptide was further
      evaluated in vivo. The result showed that this peptide had an antihypertensive
      effect in spontaneously hypertensive rats (SHRs) at a dosage of 10 mg/kg.
      Furthermore, Lineweaver-Burk plots suggested that HLFGPPGKKDPV played as a non
      competitive inhibitor against ACE, as supported by docking simulation. These data
      indicated that a fertilized egg has potential as antihypertensive components in
      functional foods and nutraceuticals. 

PMID- 24866330
TI  - Spectral evidence for hydrogen-induced reversible segregation of CO adsorbed on
      titania-supported rhodium.
AB  - The reduction of a 1.3% Rh/TiO2 sample with carbon monoxide leads to the
      formation of uniform Rh nanoparticles with a mean diameter of dp ~ 2.2 nm.
      Adsorption of CO on the reduced Rh/TiO2 produces linear and bridged carbonyls
      bound to metallic Rh(0) sites and only a few geminal dicarbonyls of Rh(I). The
      nu(CO) of linear Rh(0)-CO complexes is strongly coverage dependent: it is
      observed at 2078 cm(-1) at full coverage and at ca. 2025 cm(-1) at approximated
      zero coverage. At low coverage, this shift is mainly caused by a dipole-dipole
      interaction between the adsorbed CO molecules while at high coverage, the
      chemical shift also becomes important. Hydrogen hardly affects the CO adlayer at
      high CO coverages. However, on a partially CO-covered surface (thetaCO ~ 0.5),
      the adsorption of H2 at increasing pressure leads to a gradual shift in the band
      of linear Rh(0)-CO from 2041 to 2062 cm(-1). Subsequent evacuation almost
      restores the original spectrum, demonstrating the reversibility of the hydrogen
      effect. Through the use of (12)CO + (13)CO isotopic mixtures, it is established
      that the addition of hydrogen to the CO-Rh/TiO2 system leads to an increase in
      the dynamic interaction between the adsorbed CO molecules. This evidences an
      increase in the density of the adsorbed CO molecules and indicates segregation of
      the CO and hydrogen adlayers. When CO is adsorbed on a hydrogen-precovered
      surface, the carbonyl band maximum is practically coverage independent and is
      observed at 2175-2173 cm(-1). These results are explained by a model according to
      which CO successively occupies different rhodium nanoparticles. 

PMID- 24866325
TI  - Survey for hantaviruses, tick-borne encephalitis virus, and Rickettsia spp. in
      small rodents in Croatia.
AB  - In Croatia, several rodent- and vector-borne agents are endemic and of medical
      importance. In this study, we investigated hantaviruses and, for the first time,
      tick-borne encephalitis virus (TBEV) and Rickettsia spp. in small wild rodents
      from two different sites (mountainous and lowland region) in Croatia. In total,
      194 transudate and tissue samples from 170 rodents (A. flavicollis, n=115; A.
      agrarius, n=2; Myodes glareolus, n=53) were tested for antibodies by indirect
      immunofluorescence assays (IIFT) and for nucleic acids by conventional
      (hantaviruses) and real-time RT-/PCRs (TBEV and Rickettsia spp.). A total of
      25.5% (24/94) of the rodents from the mountainous area revealed specific
      antibodies against hantaviruses. In all, 21.3% (20/94) of the samples from the
      mountainous area and 29.0% (9/31) from the lowland area yielded positive results
      for either Puumala virus (PUUV) or Dobrava-Belgrade virus (DOBV) using a
      conventional RT-PCR. All processed samples (n=194) were negative for TBEV by IIFT
      or real-time RT-PCR. Serological evidence of rickettsial infection was detected
      in 4.3% (4/94) rodents from the mountainous region. Another 3.2% (3/94) rodents
      were positive for Rickettsia spp. by real-time PCR. None of the rodents (n=76)
      from the lowland area were positive for Rickettsia spp. by real-time PCR. Dual
      infection of PUUV and Rickettsia spp. was found in one M. glareolus from the
      mountainous area by RT-PCR and real-time PCR, respectively. To our knowledge,
      this is the first detection of Rickettsia spp. in small rodents from Croatia.
      Phylogenetic analyses of S- and M-segment sequences obtained from the two study
      sites revealed well-supported subgroups in Croatian PUUV and DOBV. Although
      somewhat limited, our data showed occurrence and prevalence of PUUV, DOBV, and
      rickettsiae in Croatia. Further studies are warranted to confirm these data and
      to determine the Rickettsia species present in rodents in these areas.

PMID- 24866331
TI  - Period3 VNTR polymorphism influences the time-of-day pain onset of acute
      myocardial infarction with ST elevation.
AB  - It is well established that the incidence and infarct size in acute myocardial
      infarction (AMI) is subject to circadian variations. At the molecular level,
      circadian clocks in distinct cells, including cardiomyocytes, generate 24-h
      cycles of biochemical processes. Possible imbalance or impairment in the cell
      clock mechanism may alter the cardiac metabolism and function and increase the
      susceptibility of cardiovascular diseases. One of the key components of the human
      clock system PERIOD3 (PER3) has been recently demonstrated to affect circadian
      expression of various genes in different tissues, including the heart. The
      variable number tandem repeat (VNTR) polymorphism (rs57875989) in gene Period3
      (Per3) is related to multiple phenotypic parameters, including diurnal
      preference, sleep homeostasis, infection and cancer. The aim of our study was to
      investigate the effect of this polymorphism in AMI with ST elevation (STEMI). The
      study subjects (314 patients of Caucasian origin with STEMI, and 332 healthy
      controls) were genotyped for Per3 VNTR polymorphism using an allele-specific
      polymerase chain reaction. A gender difference in circadian rhythmicity of pain
      onset was observed with significant circadian pattern in men. Furthermore, the
      Per3(5/5) variant carriers were associated with higher levels of interleukin-6, B
      type natriuretic peptide and lower vitamin A levels. By using cosinor analysis we
      observed different circadian distribution patterns of AMI onset at the level of
      genotype and allelic frequencies. Genotypes with at least one 4-repeat allele
      (Per3(4/5) and Per3(4/4)) (N = 264) showed remarkable circadian activity in
      comparison with Per3(5/5) (N = 50), especially in men. No significant differences
      in genotype and/or allele frequencies of Per3 VNTR polymorphism were observed
      when comparing STEMI cases and controls. Our results indicate that the Per3 VNTR
      may contribute to modulation of cardiac functions and interindividual differences
      in development and progression of myocardial infarction.

PMID- 24866329
TI  - Effects of sitagliptin or mitiglinide as an add-on to acarbose on daily blood
      glucose fluctuations measured by 72 h subcutaneous continuous glucose monitoring
      in Japanese patients with type 2 diabetes: a prospective randomized study.
AB  - OBJECTIVE: Postprandial hyperglycemia and blood glucose fluctuations increase the
      risk of macroangiopathy in patients with type 2 diabetes mellitus (T2DM).
      However, few studies have examined the effects of oral hypoglycemic drugs on
      blood glucose fluctuations in daily life. METHODS: Twenty-nine T2DM patients
      treated with acarbose were randomized to receive either sitagliptin (14 patients)
      or mitiglinide (15 patients) together with acarbose for 4 weeks. Patients were
      then switched to a combination of 10 mg mitiglinide and 0.2 mg voglibose for 4
      weeks. All patients wore a continuous glucose monitoring (CGM) device for 5 - 7
      days in week 3 of each treatment period. RESULTS: The percentage of blood glucose
      levels in the hyperglycemic range, blood glucose indices derived from 24-h CGM
      profiles and the glycemic parameters (HbA1c, glycated albumin and fasting plasma
      glucose) were significantly improved by adding sitagliptin or mitiglinide to
      ongoing acarbose therapy. These parameters also tended to improve in the
      mitiglinide/voglibose combination period. CONCLUSION: Daily blood glucose
      fluctuations were significantly improved by adding sitagliptin or mitiglinide to
      acarbose, and improved after switching to the mitiglinide/voglibose combination.
      Larger controlled studies are needed to verify the effects of adding sitagliptin
      or mitiglinide to acarbose on glucose fluctuations.

PMID- 24866332
TI  - The need for heuristics in ecosystem approaches to health.

PMID- 24866333
TI  - Cloacal aerobic bacterial flora and absence of viruses in free-living slow worms
      (Anguis fragilis), grass snakes (Natrix natrix) and European Adders (Vipera
      berus) from Germany.
AB  - Disease problems caused by viral or bacterial pathogens are common in reptiles
      kept in captivity. There is no information available on the incidence of viral
      pathogens or the physiological cloacal bacterial flora of common free-living
      reptiles in Germany. Therefore, 56 free-living reptiles including 23 European
      adders (Vipera berus), 12 grass snakes (Natrix natrix) and 21 slow worms (Anguis
      fragilis) were investigated on the island Hiddensee in northeastern Germany.
      Pharyngeal and cloacal swabs were taken immediately after capture.
      Bacteriological examination was performed from the cloacal swabs to study the
      aerobic cloacal flora. Molecular biological examination included amplification of
      DNA or RNA from adeno-, rana- and ferlaviruses as well as culturing on Russell's
      viper heart cells for virus isolation. Salmonella spp. were isolated from
      European adders but not from the other reptiles examined. The minimal inhibitory
      concentration was determined from the isolated Salmonella spp. However, some
      potentially human pathogenic bacteria, such as Proteus vulgaris, Aeromonas
      hydrophila, Klebsiella pneumoniae and Escherichia coli were isolated. Viruses
      were not detected in any of the examined reptiles. To the authors' best
      knowledge, the present study is the first survey of viral pathogens in free
      living snakes and slow worms in Germany and the first survey of cloacal aerobic
      bacterial flora of slow worms. 

PMID- 24866341
TI  - Design and synthesis of quinazolinone tagged acridones as cytotoxic agents and
      their effects on EGFR tyrosine kinase.
AB  - In a quest for finding potent cytotoxic molecules, we have designed and
      synthesized a new scaffold by tagging quinazolinones with an acridone moiety. The
      new acridone-4-carboximide derivatives were evaluated for their cytotoxic
      potentials against the MCF7 breast cancer cell line and three colon cancer cell
      lines (LS174T, SW1398, and WiDr). Compound 26 showed relatively potent cytotoxic
      activity among the derivatives, against all the cell lines tested. Mechanistic
      studies for the selected derivatives 7, 8, 16, 17, 25, and 26 were conducted
      through in vitro EGFR tyrosine kinase inhibition studies. The results indicate
      that compound 26 has a better EGFR tyrosine kinase inhibitory profile. The in
      vitro EGFR inhibition data was correlated with the cytotoxic properties, and
      molecular docking studies were performed with regard to the receptor
      autophosphorylation sites of the protein kinase domain of the EGFR.

PMID- 24866343
TI  - The annealing helicase and branch migration activities of Drosophila HARP.
AB  - HARP (SMARCAL1, MARCAL1) is an annealing helicase that functions in the repair
      and restart of damaged DNA replication forks through its DNA branch migration and
      replication fork regression activities. HARP is conserved among metazoans. HARP
      from invertebrates differs by the absence of one of the two HARP-specific domain
      repeats found in vertebrates. The annealing helicase and branch migration
      activity of invertebrate HARP has not been documented. We found that HARP from
      Drosophila melanogaster retains the annealing helicase activity of human HARP,
      the ability to disrupt D-loops and to branch migrate Holliday junctions, but
      fails to regress model DNA replication fork structures. A comparison of human and
      Drosophila HARP on additional substrates revealed that both HARPs are competent
      in branch migrating a bidirectional replication bubble composed of either DNA:DNA
      or RNA:DNA hybrid. Human, but not Drosophila, HARP is also capable of regressing
      a replication fork structure containing a highly stable poly rG:dC hybrid.
      Persistent RNA:DNA hybrids in vivo can lead to replication fork arrest and genome
      instability. The ability of HARP to strand transfer hybrids may signify a hybrid
      removal function for this enzyme, in vivo. 

PMID- 24866345
TI  - Short-form nutrition assessment in patients with advanced heart failure evaluated
      for ventricular assist device placement or cardiac transplantation.
AB  - BACKGROUND: It has been shown that malnutrition affects clinical outcomes in
      patients with advanced heart failure and that nutrition status, as determined by
      the Mini Nutritional Assessment (MNA), can be used as an independent predictor of
      mortality. The aim of this study was to evaluate the prognostic utility of the
      short-form MNA (MNA-SF) as a surrogate to the MNA in patients with advanced heart
      failure. METHODS: Data retrospectively gathered from nutrition assessments of 162
      patients were analyzed. RESULTS: As defined by the MNA, the cohort included 40
      (24.7%) patients classified as malnourished, 106 (65.4%) classified as at risk,
      and 16 (9.9%) classified as well nourished. The mortality for the groups was
      37.3%, 47.4%, and 40.5%, respectively. A linear regression showed strong
      correlation between the MNA and MNA-SF (r = 0.778, P < .0001). A significant
      difference was observed in survival between the undernourished state (at risk +
      malnourished) and the well-nourished state, as determined by the MNA-SF (P <
      .001). CONCLUSIONS: The MNA-SF is a rapid nutrition assessment that correlates
      strongly with the full-form MNA and is an independent predictor of mortality.

PMID- 24866344
TI  - Association between colonic diverticulosis and prevalence of colorectal polyps.
AB  - INTRODUCTION: Diverticulosis and colorectal polyps increase in frequency as the
      population ages. Proposed common mechanisms for both include lack of dietary
      fiber, increased saturated fats, and slow colonic transit time. The association
      of diverticulosis and colorectal polyps has been previously reported with
      conflicting results. Despite sharing common epidemiologic predisposing factors,
      the association between diverticulosis and colon polyps remains unclear and needs
      better clarification. AIM: The primary aim of our study is to evaluate if there
      is any association between diverticular disease and colorectal polyps. MATERIALS
      AND METHODS: This is a retrospective cohort study. All consecutive patients who
      underwent colonoscopy between January 2009 and December 2011 were included,
      except those with history of inflammatory bowel disease, polyposis syndrome, and
      poor bowel preparation. Univariate and multivariate logistic regression analysis
      was conducted to analyze the association between colon polyps and diverticulosis.
      Hyperplastic polyps were excluded from the statistical analysis, and only pre
      cancerous adenomas were included. RESULTS: A total of 2,223 patients met the
      inclusion criteria. The prevalence of colorectal polyps in patients with
      diverticulosis was significantly higher than those without diverticulosis (odds
      ratio (OR) 1.54; 95 % confidence interval (CI) 1.27-1.80, p = 0.001). This
      association was found significant for all locations of polyps and all
      histological subtypes. There was also a statistically significant association
      between age, presence of diverticulosis, and colorectal polyps (OR 1.03; 95 % CI
      1.02-1.04). The incidence of colorectal polyps increases as age advances in
      patients with diverticulosis, with the highest association in patients >70 years
      of age (OR 3.55; 95 % CI 2.50-5.04). There was no significant association between
      indication for colonoscopy and presence of colorectal polyps in patients with
      diverticulosis (OR 0.98; 95 % CI 0.95-1.01). The incidence of diverticulitis was
      low (<1 %), and there was no association between diverticulitis and colon polyps.
      CONCLUSION: There is a significant association between diverticulosis and
      synchronous pre-cancerous colorectal polyps (adenomas). Patients with
      diverticulosis have a higher risk of colorectal polyps as compared to those
      without. This observation needs further validation by a large prospective cohort
      study.

PMID- 24866346
TI  - The effects of isolated single umbilical artery on first and second trimester
      aneuploidy screening test parameters.
AB  - OBJECTIVE: Reliability of first and second trimester screening tests largely
      depends on accurate estimation of maternal serum marker values. Reduced
      reliability could lead redundant invasive tests or misdiagnosis. Adjustments of
      serum marker values for confounding factors like insulin-dependent diabetes,
      maternal weight or maternal rhesus status are essential. We aimed to investigate
      whether isolated single umbilical artery alters first and second trimester test
      parameters or not. METHODS: Routine detailed obstetric ultrasonographies
      performed were retrospectively screened for this study. Among spontaneously
      conceived singleton pregnancies, women who were found to have single umbilical
      artery without any additional structural anomalies or aneuploidies were selected.
      First and second trimester screening test results were accessible for 98 and 102
      of the cases with isolated single umbilical artery, respectively. RESULTS: Among
      first trimester screening test parameters, PAPP-A (pregnancy-associated plasma
      protein A) MoMs were found significantly higher in isolated single umbilical
      artery group. AFP MoMs were found significantly elevated in isolated single
      umbilical artery group in second trimester quadruple tests. CONCLUSION: Existence
      of single umbilical artery could alter the estimation of MoM values of maternal
      serum markers. Reliability of prenatal screening tests could be improved by
      adjusting these parameters in accordance with isolated single umbilical artery.

PMID- 24866347
TI  - Motor-vehicle injury in pregnancy and subsequent feto-maternal outcomes: of grave
      concern.
AB  - OBJECTIVES: (1) To evaluate maternal and fetal outcome after motor-vehicle injury
      during pregnancy. (2) To determine if there was prenatal care provider counseling
      for seat belt use. METHODS: Retrospective chart analysis of materno-fetal outcome
      following motor vehicle injury in 728 pregnant women between 2009 and 2012. Women
      attending antenatal clinics over these years were asked if they were counseled
      regarding correct seat belt use by prenatal health care providers during their
      antenatal visits. RESULTS: In these pregnant women, 80 (11%) sustained minor
      injuries/sprains. 648 women (89%) had severe adverse materno-fetal pregnancy
      outcomes. Important causes being: (1) placental abruption 58.8%; (2) preterm
      labor (40%); and (3) uterine rupture (1.6%). There were 100 (13.7%) maternal and
      78 (10.7%) fetal deaths. 91 (12.5%) perimortem cesarean deliveries were performed
      and 74 (81%) fetus survived, as did 31 women. Prenatal care provider counseling
      for seat belt use occurred in 44.8% of prenatal visit. Only 125 (21%) were using
      seat belt during the accident. CONCLUSION: Important causes of adverse pregnancy
      outcome were: abruptio placenta, preterm labor and uterine rupture. There were
      100 maternal and 78 fetal deaths with 97 preterm births. Counseling occurred in
      44.8% of women. Those using seat belts during the accidents sustained minor
      injuries.

PMID- 24866348
TI  - Water immersion and changes in the foetoplacental and uteroplacental circulation:
      an observational study with the case as its own control.
AB  - OBJECTIVE: To evaluate the effect of immersion into water on maternal blood
      pressure, amount of amniotic fluid and on the foetoplacental- and uteroplacental
      circulation in healthy women with an uncomplicated singleton pregnancy. METHODS:
      Twenty-five healthy women were included. Recordings of blood pressure, deepest
      vertical pocket of amniotic fluid and pulsatility index (PI) measured by Doppler
      in the umbilical and uterine arteries were obtained. The participants were
      immersed into water and the measurements were repeated after 5 and 25 min in
      water and again 15 and 30 min post immersion. RESULTS: The amount of amniotic
      fluid increased significantly (p < 0.001), and the maternal blood pressure
      decreased significantly during immersion (p < 0.001). There was no significant
      effect of immersion on either umbilical- or uterine artery PI. All changes
      returned toward baseline-level within 30 min after immersion. CONCLUSIONS:
      Immersion into water increases the amount of amniotic fluid and decreases the
      maternal blood pressure. Immersion into water has no significant effect on either
      the foetoplacental or uteroplacental circulation. Further studies are needed in
      order to explore the effect of immersion in pregnancies complicated by a
      dysfunctional placenta.

PMID- 24866350
TI  - Maternal obesity in singleton versus twin gestations: a population-based matched
      case-control study.
AB  - OBJECTIVE: To examine the impact of pre-pregnancy obesity on adverse outcomes in
      twin compared to singleton pregnancies. METHODS: Dichorionic twin gestations with
      maternal body mass index >30 were matched to three singleton controls. Both obese
      groups were matched (1:3) with non-obese controls. Rates of preeclampsia,
      gestational diabetes, cesarean section, and preterm birth were compared. RESULTS:
      One hundred eighty-nine dichorionic twin pregnancies in obese mothers were
      matched to 567 twin pregnancies in non-obese mothers, and to 567 singleton
      pregnancies in obese mothers. The latter were matched to 1701 non-obese mothers
      with singletons. Preeclampsia was more common in obese mothers with both twins
      and singletons (odds ratio (OR) 3.95, 95% confidence interval (CI) 2.18-7.16 and
      OR 6.53, 95% CI 3.75-11.4, respectively) as was gestational diabetes (OR 4.35,
      95% CI 2.18-8.69; OR 5.53 95% CI 3.60-8.50). Obese mothers with singletons were
      more likely to deliver abdominally, but the cesarean rates were obesity
      independent in twins. Obese mothers were more likely to deliver at < 34 weeks in
      both twin and singleton groups (OR 1.65, 95% CI 1.10-2.48, and OR 2.41, 95% CI
      1.21-4.77, respectively). CONCLUSION: Obesity-attributable adverse outcomes are
      lower in twins compared to singletons. Obesity increases the risk of preterm
      birth regardless of plurality.

PMID- 24866349
TI  - Prenatal diagnosis versus first-trimester screening of trisomy 21 among pregnant
      women aged 35 or more.
AB  - OBJECTIVE: To compare the policy of prenatal diagnosis versus first trimester
      screening of trisomy 21 among pregnant women of advanced age. METHODS: A
      retrospective study was conducted on patients aged >=35 divided in two groups:
      patients who requested first trimester combined test and only in case of screen
      positive result underwent invasive testing (group A); patients undergoing
      chorionic villous sampling or amniocentesis as first investigation (group B). The
      following outcome variables were compared: antenatal detection of trisomy 21,
      occurrence of trisomy 21 at birth, miscarriage rate, hospitals' costs. RESULTS:
      4527 women were included. Of these, 534 (11.80%) underwent T21 screening whereas
      3993 (88.20%) requested primary invasive testing. In group A, 64 combined test
      were positive (11.99%) and 8 trisomy 21 cases were diagnosed (1.50%); the loss of
      euploid fetuses after invasive procedure was 4.55% (2/44). No false-negative case
      was observed. In group B 57 cases of trisomy 21 were diagnosed (1.43%), and
      pregnancy loss rate of chromosomally normal fetuses was 0.45% (17/3806). The
      estimated cost was, respectively, 67.720? for the primary screening versus
      1.996.500? for direct prenatal diagnosis. CONCLUSION: First trimester screening
      of trisomy 21 is highly accurate and cost saving among women >=35.

PMID- 24866351
TI  - Maternal outcomes according to mode of delivery in women with severe
      preeclampsia: a cohort study.
AB  - OBJECTIVE: To determine the association between mode of delivery and maternal
      complications in patients with severe preeclampsia. METHODS: A prospective cohort
      study was conducted with 500 pregnant women with severe preeclampsia. The mode of
      delivery, vaginal or caesarean section, was considered the exposure, while the
      postpartum maternal complications and severe maternal morbidity were the
      outcomes. Logistic regression analysis was performed to determine the adjusted
      risk and 95% confidence intervals (95% CI) of maternal morbidity. RESULTS: Labour
      was spontaneous in 22.0% and induced in 28.2%, while 49.8% had an elective
      caesarean section. Ninety-five (67.4%) of the patients in whom labour was induced
      delivered vaginally. Total Caesarean rate was 68.2%. The risk of severe maternal
      morbidity was significantly greater in patients submitted to Caesarean section
      (54.0% versus 32.7%) irrespective of the presence of labour. Factors that
      remained associated with severe maternal morbidity following multivariate
      analysis were a diagnosis of HELLP syndrome after delivery (OR = 3.73; 95% CI:
      1.55-9.88) and having a caesarean (OR = 1.91; 95% CI: 1.52-4.57). CONCLUSIONS:
      Caesareans are often performed in patients with severe preeclampsia and are
      associated with significant postpartum maternal morbidity. Induction of labour
      should be considered a feasible option in these patients.

PMID- 24866352
TI  - Pregnancy in patients with sickle cell disease: maternal and perinatal outcomes.
AB  - OBJECTIVE: To compare obstetrical, hematological and neonatal outcomes of
      pregnant women with or without sickle cell disease (SCD). METHODS: A prospective
      study of 60 pregnancies of 58 women with SCD (29 SCD-SS and 29 SCD-SC) compared
      with 192 pregnancies in 187 healthy pregnant women was carried out from January
      2009 to August 2011. RESULTS: Compared to controls, the SCD group had higher rate
      of preterm delivery (p < 0.001, OR = 4.96, 95% CI 2.57-9.59), higher cesarean
      rate (p < 0.001, OR = 5.00, CI 2.65-9.45), more frequent deep vein thrombosis (p
      = 0.003), and urinary infection (p = 0.001, OR = 3.31, CI 1.63-6.73), higher
      prevalence of small for gestational age babies (p = 0.019, OR = 2.66, CI 1.15
      6.17), and more frequent baby admissions to progressive care unit (p < 0.001, OR
      = 4.89, CI 2.26-10.6). Maternal death rate was also higher among women with SCD
      (p = 0.056). All adverse events were more frequent in the SS subgroup. Babies
      from the SS subgroup had the lowest weight at birth (2080 g) compared to SC (2737
      g; p < 0.001) and controls (3035 g). A multivariate analysis confirmed painful
      episodes and SS genotype as factors contributing to preterm delivery. CONCLUSION:
      SCD pregnant women - especially those in the SS subgroup - are more prone to
      experience perinatal and maternal complications in comparison with pregnant women
      without SCD.

PMID- 24866342
TI  - Cellular senescence and protein degradation: breaking down cancer.
AB  - Autophagy and the ubiquitin-proteasome pathway (UPP) are the major protein
      degradation systems in eukaryotic cells. Whereas the former mediate a bulk
      nonspecific degradation, the UPP allows a rapid degradation of specific proteins.
      Both systems have been shown to play a role in tumorigenesis, and the interest in
      developing therapeutic agents inhibiting protein degradation is steadily growing.
      However, emerging data point to a critical role for autophagy in cellular
      senescence, an established tumor suppressor mechanism. Recently, a selective
      protein degradation process mediated by the UPP was also shown to contribute to
      the senescence phenotype. This process is tightly regulated by E3 ubiquitin
      ligases, deubiquitinases, and several post-translational modifications of target
      proteins. Illustrating the complexity of UPP, more than 600 human genes have been
      shown to encode E3 ubiquitin ligases, a number which exceeds that of the protein
      kinases. Nevertheless, our knowledge of proteasome-dependent protein degradation
      as a regulated process in cellular contexts such as cancer and senescence remains
      very limited. Here we discuss the implications of protein degradation in
      senescence and attempt to relate this function to the protein degradation pattern
      observed in cancer cells. 

PMID- 24866353
TI  - Effects of excessive speeding and falling asleep while driving on crash injury
      severity in Ethiopia: a generalized ordered logit model analysis.
AB  - The severity of injury from vehicle crash is a result of a complex interaction of
      factors related to drivers' behavior, vehicle characteristics, road geometric and
      environmental conditions. Knowing to what extent each factor contributes to the
      severity of an injury is very important. The objective of the study was to assess
      factors that contribute to crash injury severity in Ethiopia. Data was collected
      from June 2012 to July 2013 on one of the main and busiest highway of Ethiopia,
      which extends from the capital Addis Ababa to Hawassa. During the study period a
      total of 819 road crashes was recorded and investigated by trained crash
      detectors. A generalized ordered logit/partial proportional odds model was used
      to examine factors that might influence the severity of crash injury. Model
      estimation result suggested that, alcohol use (Coef.=0.5565; p-value=0.017),
      falling asleep while driving (Coef.=1.3102; p-value=0.000), driving at night time
      in the absence of street light (Coef.=0.3920; p-value=0.033), rainfall
      (Coef.=0.9164; p-value=0.000) and being a minibus or vans (Coef.=0.5065; p
      value=0.013) were found to be increased crash injury severity. On the other hand,
      speeding was identified to have varying coefficients for different injury levels,
      its highest effects on sever and fatal crashes. In this study risky driving
      behaviors (speeding, alcohol use and sleep/fatigue) were a powerful predictor of
      crash injury severity. Therefore, better driver licensing and road safety
      awareness campaign complimented with strict police enforcement can play a pivotal
      role to improve road safety. Further effort needed as well to monitor speed
      control strategies like; using the radar control and physical speed restraint
      measures (i.e., rumble strips). 

PMID- 24866354
TI  - Utility of quantitative EBV DNA measurements in cerebrospinal fluid for diagnosis
      and monitoring of treatment of central nervous system EBV-associated post
      transplant lymphoproliferative disorder after allogenic hematopoietic stem cell
      transplantation.
AB  - BACKGROUND: Epstein-Barr virus (EBV)-associated post-transplant
      lymphoproliferative disorder (PTLD) after hematopoietic stem cell transplantation
      (HSCT) is a rare but life- threatening condition. Despite routine EBV DNA-emia
      monitoring in blood, central nervous system involvement of the disease is still
      associated with diagnostic difficulties and poor outcome. CASE REPORT: We
      describe a 17-year-old female patient with severe aplastic anemia who developed
      central nervous system EBV-associated PTLD after matched unrelated allo-HSCT. EBV
      DNA concentration in cerebrospinal fluid was initially tested due to central
      nervous system-related symptoms. The sample was found to be highly EBV DNA
      positive. Using quantitative real-time polymerase chain reaction (PCR)
      measurements, therapy efficiency was monitored until complete remission of the
      EBV-associated PTLD. CONCLUSIONS: The case report illustrates the high utility of
      quantitative real-time PCR EBV measurements in cerebrospinal fluid for rapid
      diagnosis and therapy monitoring of central nervous system EBV-associated PTLDs
      after allo-HSCT.

PMID- 24866355
TI  - Utility and efficacy of a smartphone application to enhance the learning and
      behavior goals of traditional cardiac rehabilitation: a feasibility study.
AB  - PURPOSE: Most eligible patients do not participate in traditional clinic-based
      cardiac rehabilitation (CR) despite well-established benefits. Novel approaches
      to overcome logistic obstacles and increase efficiencies of learning, behavior
      modification, and exercise surveillance may increase CR participation. In an
      observational study, the feasibility and utility of a mobile smartphone
      application for CR, Heart Coach (HC), were assessed as part of standard care.
      Ultimately, innovative CR models incorporating HC may facilitate better CR usage
      and value. METHODS: Twenty-six patients enrolled in CR installed HC. Over the
      next 30 days, they were prompted by HC to complete a daily "task list" that
      included medications, walking, education (text and videos), and surveys. Cardiac
      rehabilitation providers monitored each patient's progress through a HC-based Web
      dashboard and also sent them personalized feedback and support. Completion of the
      tasks and feedback (qualitative and quantitative) from patients and clinicians
      were tracked. RESULTS: Patients engaged with HC 90% of days during the study
      period, with uniformly favorable impact on compliance and adherence. Eighty-three
      percent of patients reported a positive/very positive HC experience. Providers
      reported that HC enhanced their provision of therapy by improving communication,
      clinical insight, patient participation, and program efficiency. CONCLUSIONS:
      Integrating a mobile care delivery platform into CR was feasible, safe, and
      agreeable to patients and clinicians. It enhanced patient perceptions of CR care
      and physician perceptions of the CR caregiving process. Mobile-enabled
      technologies hold promise to extend the quality and reach of CR, and to better
      achieve contemporary accountable care goals.

PMID- 24866356
TI  - Commercial insurance coverage for outpatient cardiac rehabilitation in patients
      with heart failure in the United States.
AB  - BACKGROUND: Although cardiac rehabilitation (CR) improves outcomes in patients
      with heart failure (HF), studies suggest variable uptake by patients with HF, as
      well as variable coverage by insurance carriers. The purpose of this study was to
      determine the percentage of large commercial health insurance companies that
      provide coverage for outpatient (CR) for patients with HF. METHODS: We identified
      a sample of the largest US commercial health care providers and analyzed their CR
      coverage policies for patients with HF. We surveyed 44 large private health care
      insurance companies, reviewed company Web sites, and, when unclear, contacted
      companies by e-mail or telephone. We excluded insurance clearinghouses because
      they did not directly provide health care insurance. RESULTS: Of 44 eligible
      insurance companies, 29 (66%) reported that they provide coverage for outpatient
      CR in patients with HF. The majority of companies (83%) covered CR for patients
      with any type of HF. A minority (10%) did not cover CR for patients with HF if it
      was considered a preexisting condition. CONCLUSIONS: A significant percentage of
      commercial health care insurance companies in the United States report that they
      currently cover outpatient CR for patients with HF. Because health insurance
      coverage is associated with patient participation in CR, it is anticipated that
      patients with HF will increasingly participate in CR in coming years.

PMID- 24866357
TI  - Clinical benefits of home-based pulmonary rehabilitation in patients with chronic
      obstructive pulmonary disease.
AB  - PURPOSE: To evaluate the benefits of home-based pulmonary rehabilitation (PR) in
      patients with severe and very severe chronic obstructive pulmonary disease
      (COPD). METHODS: Randomized clinical trial involving 58 patients. Pulmonary
      function, quality of life evaluated by the Saint George Respiratory
      Questionnaire, breathlessness evaluated by the London Chest Activity of Daily
      Living Scale, and exercise tolerance evaluated by 6-minute walk distance were
      assessed at baseline and at 12 weeks. The program consisted of 2 weekly visits by
      a physiotherapist in the first 2 weeks, followed by visits twice a month, as well
      as weekly telephone calls. Training included breathing and stretching exercises
      and strength exercises (upper and lower limbs), along with endurance training,
      including walking, stair climbing, cycling, and treadmill walking, depending on
      available patient resources. RESULTS: The treatment group (TG; n = 23) and
      control group (CG; n = 18) completed the study. Following the intervention, no
      statistically significant differences were found in pulmonary function in the TG
      and CG. The TG exhibited statistically significant differences in the activity
      domain (P = .008), impact domain (P < .001), and total scores of the Saint George
      Respiratory Questionnaire (P < .001). In addition, the TG demonstrated
      statistically significant differences in all domains of the London Chest Activity
      of Daily Living Scale and no differences were observed in the CG after 12 weeks.
      There was a statistically significant difference in the 6-Minute Walk Distance in
      the TG after rehabilitation (P = .008). CONCLUSIONS: This study offers evidence
      that home-based PR promotes benefits in the quality of life, breathlessness in
      activities of daily living, and exercise capacity in patients with severe and
      very severe COPD. Home-based PR must be considered as part of the treatment for
      patients who live far from hospitals even in severe COPD.

PMID- 24866358
TI  - [Clinical management and nursing knowledge in the change process].

PMID- 24866359
TI  - [What are the feelings of the parents towards the nurses who care for their
      newborn admitted to a neonatal intensive care unit?].

PMID- 24866360
TI  - [Living with chronic heart failure: a review of qualitative studies in the
      elderly].

PMID- 24866361
TI  - Deductive Versus Probabilistic Reasoning in Healthy Adults: An EEG Analysis of
      Neural Differences.
AB  - This study examined the electrophysiological signatures of deductive and
      probabilistic reasoning. Deduction is defined as the case in which a conclusion
      can be found to be true or false due to validity of argument. In probabilistic
      reasoning, however, conclusions can be considered to be likely or unlikely, but
      not with certainty due to the lack of validity in the form of the argument. 16
      participants were presented with both types of arguments while response times and
      ERPs were carried out. Participants had to decide with the presentation of each
      argument, what type of reasoning was appropriate and which of four responses
      (certainly yes, probably yes, probably no and certainly no) was the most
      appropriate. Response times indicated faster processing of deductive arguments.
      N2 amplitude distinguished between positive and negative responses in the
      deductive condition, but not in the probabilistic one, suggesting partial
      differentiation between the cognitive processes required for the two types of
      reasoning. 

PMID- 24866364
TI  - Provider-initiated HIV testing and counselling for children.

PMID- 24866365
TI  - Sineoculis homeobox homolog 1 protein as an independent biomarker for gastric
      adenocarcinoma.
AB  - Sine oculis homeobox homolog 1 (SIX1) protein is a member of the homeobox
      transcription factor family. Overexpression of SIX1 contributes to cancer
      progression and is associated with adverse outcomes in various cancer types
      including breast, ovarian, uterine cervical and liver. To investigate the
      clinicopathological significance of SIX1 protein expression in gastric
      adenocarcinomas (GAC), localization of the SIX1 protein was determined in MKN-1,
      a gastric cancer cell line, using immunofluorescence (IF) staining; SIX1 mRNA
      level was detected in fresh tissues of GAC and normal gastric mucosa using
      quantitative real-time polymerase chain reaction (qRT-PCR); and SIX1 protein
      expression was assessed in 163 GAC, 35 gastric dysplasia and 26 normal gastric
      mucosa using immunohistochemical (IHC) staining. Correlations between SIX1
      protein expression and pathological parameters of GAC were analyzed using Chi
      square tests, differences in survival curves were analyzed using log-rank tests,
      and multivariate survival analysis was performed using the Cox proportional
      hazards regression model. SIX1 protein showed a mainly cytoplasmic staining
      pattern in GAC using IF and IHC staining. The positive SIX1 protein expression
      rate was 80.4% in GAC, which was significantly higher than in either gastric
      dysplasia (45.7%) or normal gastric mucosa (26.9%) (P<0.01). qRT-PCR data also
      confirmed increased levels of SIX1 mRNA expression in GAC compared with the
      normal gastric mucosa in fresh tissues. In addition, the strongly positive SIX1
      protein expression rate was significantly correlated with clinical stage, lymph
      node metastasis and serosal invasion of GAC (P<0.01 or P<0.05), while there was
      no association with gender, age, tumor size, Lauren classification or
      histological types of GAC. Notably, strongly positive signals were frequently
      observed in tumor blood vessels and/or lymphatic vessels. GAC patients with high
      expression of the SIX1 had shorter overall and disease-free survival rates than
      those with low SIX1 protein expression (P<0.01). Furthermore, using multivariate
      analysis, SIX1 protein expression was found to be an independent risk factor for
      survival in patients with GAC along with clinical stage and serosal invasion
      (P<0.01). In conclusion, SIX1 protein expression status may be an independent
      biomarker for prognostic evaluation of GAC. 

PMID- 24866366
TI  - First norovirus outbreaks associated with consumption of green seaweed
      (Enteromorpha spp.) in South Korea.
AB  - In February 2012, an outbreak of gastroenteritis was reported in school A; a
      successive outbreak was reported at school B. A retrospective cohort study
      conducted in school A showed that seasoned green seaweed with radishes (relative
      risk 7.9, 95% confidence interval 1.1-56.2) was significantly associated with
      illness. Similarly, a case-control study of students at school B showed that
      cases were 5.1 (95% confidence interval 1.1-24.8) times more likely to have eaten
      seasoned green seaweed with pears. Multiple norovirus genotypes were detected in
      samples from students in schools A and B. Norovirus GII.6 isolated from schools A
      and B were phylogenetically indistinguishable. Green seaweed was supplied by
      company X, and norovirus GII.4 was isolated from samples of green seaweed. Green
      seaweed was assumed to be linked to these outbreaks. To our knowledge, this is
      the first reported norovirus outbreak associated with green seaweed.

PMID- 24866367
TI  - Detection of TEM-, SHV- and CTX-M-type beta-lactamase production among clinical
      isolates of Salmonella species.
AB  - Enteric fever is a major public health problem in developing countries. Due to
      the problem of resistance to first-line drugs and fluoroquinolone, cephalosporins
      are currently used for treatment of enteric fever. Cephalosporin resistance in
      Salmonella spp. is mainly due to production of extended-spectrum beta-lactamases
      (ESBLs). The majority of ESBLs in Salmonella are derivatives of the TEM and SHV
      beta-lactamase families. The objectives of this study were to detect antibiotic
      susceptibility patterns, ESBL production and TEM-, SHV- and CTX-M-encoding genes
      (blaTEM, blaSHV and blaCTX-M) among clinical isolates of Salmonella spp. A total
      of 134 Salmonella isolates [Salmonella Typhi (n = 101), Salmonella Paratyphi A (n
      = 31), Salmonella Paratyphi B (n = 1) and Salmonella Typhimurium (n = 1)] were
      included in this study. Multidrug resistance was seen in 5/134 (3.73%) isolates,
      all of which belonged to serotype S. Typhi. A better susceptibility profile was
      observed for first-line drugs (ampicillin, chloramphenicol, co-trimoxazole and
      tetracycline) and cephalosporins (cefotaxime, ceftazidime, ceftriaxone, cefixime
      and cefepime). However, 131 (97.76%) of the 134 isolates were resistant to
      nalidixic acid and one (0.75%) was resistant to ciprofloxacin. TEM-1-type beta
      lactamase (blaTEM-1) was detected in six (4.47%) of the 134 isolates, which
      belonged to the serotype S. Typhi. All six TEM-positive isolates were negative
      for the blaSHV gene and none of the isolates was positive for the blaCTX-M gene.
      The presence of the blaTEM gene encoding TEM-1 beta-lactamase is believed to
      confer resistance only to penicillins and early cephalosporins; however, the
      resistance spectrum of TEM-1 descendants may extend to second-, third- and fourth
      generation cephalosporins. The ESBLs derived from TEM-1 differ from their
      progenitors by as few as 1 aa, and have the ability to hydrolyse third-generation
      cephalosporins. Therefore, appropriate selection and rotation of antibiotics as
      well as continuous monitoring of antibiotic susceptibility profiles could help to
      control the emergence and spread of resistant strains.

PMID- 24866368
TI  - Sequential outbreaks in a Spanish hospital caused by multiresistant OXA-58
      producing Acinetobacter baumannii ST92.
AB  - The aim of this study was to assess the epidemiology and molecular basis of the
      infection and dissemination of multidrug-resistant Acinetobacter baumannii
      (MDRAB) in three sequential outbreaks at the intensive care units (ICUs) of a
      tertiary university hospital in Granada, Spain, between 2009 and 2011. Strains
      from all patients infected and/or colonized by MDRAB during outbreak periods were
      characterized using PFGE and multilocus sequence typing (MLST). The first
      outbreak appeared in the summer of 2009 involving 38 ICU patients: 25 from a
      Traumatology-Rehabilitation hospital (TRH) and 13 from a Medical-Surgery hospital
      (MSH). Between 2010 and 2011, outbreaks were limited to the MSH-ICU, affecting 9
      and 11 patients, respectively. Two PFGE types were detected. In the 2009
      outbreak, two clones were identified: profile 1 strains were isolated at the TRH,
      whilst profile 2 was isolated at the MSH. Only one clone was identified in the
      2010 and 2011 outbreaks: the profile 2 clone detected at the MSH in 2009. After
      MLST analysis, a single sequence type (ST92) was identified. This suggested that
      an endemic strain could evolve and cause localized outbreaks in vulnerable
      patients. Multiplex PCR for OXA group enzymes yielded a positive result for
      blaOXA-58-like and blaOXA-51-like genes, and gene sequencing showed the presence
      of blaOXA-58. However, the absence of ISAba1 upstream of the blaOXA-51-like gene
      suggested the absence of OXA-51 expression. The susceptibility pattern was not an
      appropriate method for MDRAB surveillance, as several susceptibility patterns
      were identified in a single clone. Consequently, molecular methods of
      characterization are recommended for epidemiological surveillance of MDRAB. 

PMID- 24866369
TI  - Increasing age is a predictor of short-term outcomes in esophagectomy: a
      propensity score adjusted analysis.
AB  - BACKGROUND: Esophagectomy is a high-risk surgical procedure. As the population
      ages, more elderly candidates are being evaluated for esophagectomy. The effects
      of patient age on outcomes after esophagectomy need to be evaluated. STUDY
      DESIGN: We identified all nonemergent esophagectomies in patients at least 18
      years of age within the University HealthSystems Consortium Clinical
      Database/Resource Manager from 2009 to 2012. Using univariate and multivariate
      methods, the impact of increasing age on outcomes was analyzed. Additionally,
      propensity scoring was used to match patients to further investigate the effect
      of age on the stated outcomes. RESULTS: Increasing age is associated with
      increased mortality (p < 0.001), length of stay (p < 0.001), discharge to
      rehabilitative care (p < 0.001), and cost (p < 0.001). The effects of age on
      mortality (8.0 vs 4.2 %, p = 0.03) and discharge to rehabilitative care (44.1 vs
      23.4 %, p < 0.01) were confirmed using propensity scoring, comparing patients
      above 80 with those age 70-79. CONCLUSIONS: Increasing age has a significant
      impact on outcomes following esophagectomy, particularly mortality and discharge
      disposition. Compared to patients under age 80, patients at least 80 years of age
      considering esophagectomy should be recognized as a high-risk cohort, and these
      patients must be carefully risk-stratified, counseled, and selected for surgical
      intervention to prevent unnecessary hospitalization and mortality.

PMID- 24866370
TI  - Prevalence and correlates of posttrauma distorted beliefs: evaluating DSM-5 PTSD
      expanded cognitive symptoms in a national sample.
AB  - The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders
      (DSM-5; American Psychiatric Association [APA], 2013) modified the diagnostic
      criteria for posttraumatic stress disorder (PTSD), including expanding the scope
      of dysfunctional, posttrauma changes in belief (symptoms D2-persistent negative
      beliefs and expectations about oneself or the world, and D3-persistent distorted
      blame of self or others for the cause or consequences of the traumatic event). D2
      and D3 were investigated using a national sample of U.S. adults (N = 2,498)
      recruited from an online panel. The prevalence of D2 and D3 was substantially
      higher among those with lifetime PTSD than among trauma-exposed individuals
      without lifetime PTSD (D2: 74.6% vs 23.9%; D3: 80.6% vs 35.7%). In multivariate
      analyses, the strongest associates of D2 were interpersonal assault (OR = 2.39),
      witnessing interpersonal assault (OR = 1.63), gender (female, OR = 2.11), and
      number of reported traumatic events (OR = 1.88). The strongest correlates of D3
      were interpersonal assault (OR = 3.08), witnessing interpersonal assault (OR =
      1.57), gender (female, OR = 2.30), and number of reported traumatic events (OR =
      1.91). The findings suggested the expanded cognitive symptoms in the DSM-5
      diagnostic criteria better capture the cognitive complexity of PTSD than those of
      the DSM-IV. 

PMID- 24866372
TI  - Current patterns of water and beverage consumption among Mexican children and
      adolescents aged 1-18 years: analysis of the Mexican National Health and
      Nutrition Survey 2012.
AB  - OBJECTIVE: To evaluate patterns of water consumption from plain water, beverages
      and foods among Mexican children and adolescents and to compare actual patterns
      of total daily water intake with the Dietary Reference Intakes (DRI). DESIGN: We
      analysed one 24 h dietary recall from Mexican children and adolescents. We
      calculated intakes of total daily water and water from foods and from beverages.
      Actual total water intake per capita was subtracted from the DRI for water to
      calculate the shortfall. SETTING: Mexican National Health and Nutrition Survey in
      2012. SUBJECTS: Mexican children and adolescents (n 6867) aged 1-18 years.
      RESULTS: Approximately 73% of children and adolescents aged 1-18 years reported
      drinking plain water. Beverages and plain water represented 65.5% and 26.5% of
      total daily water intake, respectively. Among 1-3-year-olds, the top three main
      sources of water were from foods, plain water and water from plain milk. Among 4
      8- and 9-13-year-olds, the main sources were from foods, plain water and agua
      fresca (fruit water). Among 14-18-year-olds, the main sources of water were plain
      water, water from foods and soda. A higher proportion of 1-3-year-olds and 4-8
      year-olds met the DRI for water (38% and 29%, respectively). Among 9-13-year-olds
      and 14-18-year-olds, 13-19% of children met the DRI for water. CONCLUSIONS: Total
      daily water intakes remain below DRI levels in all age groups. Although plain
      water still contributes the greatest proportion to daily water intake among
      fluids, caloric beverages are currently major sources of water especially among
      older children and adolescents.

PMID- 24866371
TI  - Short- to mid-term results of arthroscopic meniscal repair of long vertical
      longitudinal tears using combined cruciate and horizontal suture techniques: a
      retrospective study.
AB  - INTRODUCTION: The purpose was to evaluate the clinical results of arthroscopic
      meniscal repair of long vertical longitudinal tears using combined cruciate and
      horizontal suture techniques. METHODS: Single surgeon retrospective case series
      study. A total of 38 patients having long vertical longitudinal tears were
      operated using combined cruciate and horizontal suture techniques. Two patients
      had to undergo a meniscectomy procedure within the 1st year postoperative and
      those were considered failure cases; 32 patients were available for follow-up
      evaluation (average 4.6 years) and six were lost including the two failures.
      Objective IKDC, modified Lysholm knee score, SF-36 score, VAS for patients'
      satisfaction and VAS for pain were used for follow-up evaluation. Kellgren and
      Lawrence (K/L) classification of osteoarthritis was also used. RESULTS:
      Successful rate was 94.1% (32 patients), while failure was 5.9% (2 patients).
      Objective IKDC score revealed that 27 patients had grade "A" and 5 had grade "B,"
      while no single patient had neither grade "C" nor "D." The average modified
      Lysholm score was 91.3. Average SF-36 score was 88.4. The average VAS for
      operation satisfaction was eight. Average VAS for pain was 1.5. Preoperatively,
      30 patients were classified as normal K/L classification, while two patients were
      K/L classification grade "1." At the time of the follow-up, 24 patients were
      classified as normal K/L classification, six were grade "1," two were grade "2,"
      and thus, six had osteoarthritis progression. CONCLUSION: Arthroscopic meniscal
      repair of long vertical longitudinal tears using combined cruciate and horizontal
      suture techniques is a safe surgical procedure with good clinical outcome. LEVEL
      OF EVIDENCE: Level IV.

PMID- 24866373
TI  - Self-assembled structures of anionic hydrophobically modified polyacrylamide with
      star-shaped trimeric and hexameric quaternary ammonium surfactants.
AB  - The self-assembly of a 1% hydrophobically modified and 30% hydrolyzed
      polyacrylamide (C12PAM) with cationic star-shaped oligomeric surfactants has been
      investigated by isothermal titration microcalorimetry, turbidimetry, zeta
      potential, scanning electron microscopy, and (1)H NMR techniques. The oligomeric
      surfactants are composed of quaternary dodecyldimethylammonium ions with three or
      six hydrophobic chains connected by a polyamine spacer at the headgroup level,
      abbreviated as DTAD and PAHB, respectively. DTAD/C12PAM and PAHB/C12PAM mixed
      systems undergo the same aggregate transitions with increases in surfactant
      concentration from soluble networklike aggregates to precipitated denser and more
      cross-linked structures and then to soluble spherical aggregates. The networklike
      aggregates are generated at very low surfactant concentration. However, at the
      corresponding surfactant concentration without C12PAM, DTAD cannot form
      aggregates and PAHB forms only networklike aggregates with a very loose
      structure. The strong electrostatic and hydrophobic interaction of DTAD and PAHB
      with C12PAM and the hydrophobic interaction between the alkyl chains of DTAD and
      PAHB themselves evidently promote the formation of networklike aggregates. As the
      surfactant concentration increases, cationic surfactants become excessive. The
      molecular configuration is changed by the stronger hydrophobic association among
      the DTAD and PAHB molecules and the enhanced electrostatic repulsion between the
      mixed aggregates. Thus, the networklike aggregates transfer to spherical
      aggregates. 

PMID- 24866374
TI  - Versatile O-GlcNAc transferase assay for high-throughput identification of enzyme
      variants, substrates, and inhibitors.
AB  - The dynamic glycosylation of serine/threonine residues on nucleocytoplasmic
      proteins with a single N-acetylglucosamine (O-GlcNAcylation) is critical for many
      important cellular processes. Cellular O-GlcNAc levels are highly regulated by
      two enzymes: O-GlcNAc transferase (OGT) is responsible for GlcNAc addition and O
      GlcNAcase (OGA) is responsible for removal of the sugar. The lack of a rapid and
      simple method for monitoring OGT activity has impeded the efficient discovery of
      potent OGT inhibitors. In this study we describe a novel, single-well OGT enzyme
      assay that utilizes 6 * His-tagged substrates, a chemoselective chemical
      reaction, and unpurified OGT. The high-throughput Ni-NTA Plate OGT Assay will
      facilitate discovery of potent OGT-specific inhibitors on versatile substrates
      and the characterization of new enzyme variants. 

PMID- 24866375
TI  - Cannula malposition during antegrade cerebral perfusion for aortic surgery: role
      of cerebral oximetry.
AB  - PURPOSE: To describe the use of cerebral oximetry to detect a lack of right
      cerebral perfusion resulting from a malpositioned catheter used for antegrade
      cerebral perfusion during deep hypothermic circulatory arrest (DHCA). The simple
      corrective surgical adjustment that followed averted a potentially serious
      complication. CLINICAL FEATURES: A 57-yr-old male with a type-A aortic dissection
      undergoing DHCA required antegrade cerebral perfusion for cerebral protection.
      Catheters were placed accordingly in the left common carotid and brachiocephalic
      arteries. Whereas frontal cerebral oximetry immediately improved on the left, it
      did not improve on the right. It was immediately suspected that the tip of the
      brachiocephalic cannula had advanced into the right subclavian artery, thus
      depriving the right common carotid artery of blood flow. The problem resolved
      upon slight withdrawal of the cannula. CONCLUSION: Vigilance in anesthesia should
      not stop during DHCA or cardiopulmonary bypass. Cerebral oximetry may provide
      important information leading to actions that improve brain protection.
      Vigilances proved important in this case where the cannula tip used for antegrade
      cerebral perfusion was advanced too far into the right subclavian artery.

PMID- 24866376
TI  - Airway management options in a prone achondroplastic dwarf with a difficult
      airway after unintentional tracheal extubation during a wake-up test for spinal
      fusion: to flip or not to flip?
AB  - PURPOSE: To present a case of unintentional tracheal extubation in a prone
      positioned patient with a known difficult airway. CLINICAL FEATURES: This case
      report describes the unintended tracheal extubation of an achondroplastic dwarf
      with kyphosis undergoing spinal fusion and instrumentation. The patient had a
      history of obstructive sleep apnea and a difficult airway requiring fibreoptic
      guided tracheal intubation through an air-QTM supraglottic airway device. Abrupt
      head movement during a wake-up test to evaluate lost motor-evoked potential
      signals resulted in dislodgement of the tracheal tube. Airway obstruction was
      evidenced by rapid oxygen desaturation and the absence of end-tidal capnography
      waveforms despite apparent chest excursions. An air-Q was used for successfully
      rescuing the airway and quickly re-establishing oxygenation and ventilation,
      which eliminated the need for emergent supine positioning for airway management.
      The air-Q was then used as a conduit for fibreoptic-guided tracheal intubation
      while the patient remained in the prone position. CONCLUSION: This case
      highlights some of the safety advantages of supraglottic airway devices for
      airway rescue and subsequent tracheal intubation even with the patient in the
      prone position. The use of an air-Q may have the advantages of not requiring an
      intubation introducer technique and allowing for direct tracheal intubation with
      an appropriately sized cuffed tracheal tube.

PMID- 24866377
TI  - A survey of Canadian anesthesiologists' preferences in difficult intubation and
      "cannot intubate, cannot ventilate" situations.
AB  - INTRODUCTION: The purpose of this survey was to determine the equipment that
      anesthesiologists prefer in difficult tracheal intubation and "cannot intubate,
      cannot ventilate" (CICV) situations. METHODS: A questionnaire was e-mailed to
      members of the Canadian Anesthesiologists' Society to ascertain their
      preferences, experience, and comfort level with regard to their use of airway
      equipment in difficult intubation and CICV situations in adult patients. A Chi
      square test was used to analyse the data. All reported P values are two-sided.
      RESULTS: Nine hundred ninety-seven of 2,532 questionnaires (39%) were returned.
      In an unanticipated difficult direct laryngoscopic intubation situation, 893 of
      997 (90%) respondents chose a video laryngoscope as the first-choice rescue
      technique, while 41 (4%) and 21 (2%) of respondents chose a flexible bronchoscope
      and an intubating laryngeal mask airway device, respectively. The majority of
      anesthesiologists had experience and were comfortable with using a flexible
      bronchoscope or a video laryngoscope. Regarding CICV, 294 of 955 (31%)
      respondents stated that they had never encountered it. Wire-guided
      cricothyroidotomy was chosen as the first-choice surgical airway by 375 of 955
      (39%) respondents, while intravenous catheter cricothyroidotomy and "defer to
      tracheostomy by surgeon" were selected by 266 (28%) and 215 (23%) respondents,
      respectively. Seven hundred eighty-five of 997 (78%) respondents were familiar
      with the exact steps of the American Society of Anesthesiologists' difficult
      airway algorithm, while 448 (47%) had attended an airway workshop within the past
      five years. CONCLUSIONS: In a difficult intubation situation, the most frequently
      selected first-choice airway device was a video laryngoscope, followed by a
      flexible bronchoscope. In a CICV situation, the most frequently selected first
      choice surgical airway technique was a wire-guided cricothyroidotomy, followed by
      an intravenous catheter cricothyroidotomy.

PMID- 24866379
TI  - Visualizing energy landscapes with metric disconnectivity graphs.
AB  - The visualization of multidimensional energy landscapes is important, providing
      insight into the kinetics and thermodynamics of a system, as well the range of
      structures a system can adopt. It is, however, highly nontrivial, with the number
      of dimensions required for a faithful reproduction of the landscape far higher
      than can be represented in two or three dimensions. Metric disconnectivity graphs
      provide a possible solution, incorporating the landscape connectivity information
      present in disconnectivity graphs with structural information in the form of a
      metric. In this study, we present a new software package, PyConnect, which is
      capable of producing both disconnectivity graphs and metric disconnectivity
      graphs in two or three dimensions. We present as a test case the analysis of the
      69-bead BLN coarse-grained model protein and show that, by choosing appropriate
      order parameters, metric disconnectivity graphs can resolve correlations between
      structural features on the energy landscape with the landscapes energetic and
      kinetic properties.

PMID- 24866378
TI  - Protease-activated receptor 1 suppresses Helicobacter pylori gastritis via the
      inhibition of macrophage cytokine secretion and interferon regulatory factor 5.
AB  - Chronic gastritis from Helicobacter pylori infection is a major factor in the
      development of gastric adenocarcinoma. Factors that regulate gastritis severity
      are important in determining which individuals are susceptible to H. pylori
      associated disease. Although protease-activated receptor 1 (PAR1) has been
      identified as one such host factor, its mechanism of action is unknown. Using
      chimeric mice, we demonstrated that PAR1-mediated protection against H. pylori
      gastritis requires bone marrow-derived cells. Analyses of the gastric mucosa
      revealed that PAR1 suppresses cellular infiltration and both T helper type 1
      (Th1) and T helper type 17 (Th17) responses to infection. Moreover, PAR1
      expression was associated with reduced vaccine-mediated protection against H.
      pylori. Analyses of H. pylori-stimulated macrophages revealed that PAR1
      activation suppressed secretion of interleukin (IL)-12 and IL-23, key drivers of
      Th1 and Th17 immunity, respectively. Furthermore, PAR1 suppressed interferon
      regulatory factor 5 (IRF5), an important transcription factor for IL-12 and IL
      23, both in the infected mucosa and following bacterial stimulation. PAR1
      suppression of IRF5 and IL-12/23 secretion by macrophages provides a novel
      mechanism by which the host suppresses the mucosal Th1 and Th17 response to H.
      pylori infection. Dysregulation of this process is likely an important factor in
      the susceptibility of some individuals to H. pylori-associated disease. 

PMID- 24866380
TI  - A polymorphism in the TH 2 locus control region is associated with changes in DNA
      methylation and gene expression.
AB  - BACKGROUND: Genomewide association and epigenetic studies found a region within
      the RAD50 gene on chromosome 5q31 to be associated with total serum IgE levels
      and asthma. In mice, this region harbors a locus control region for nearby TH 2
      cytokines, which is characterized by four Rad50 DNase I hypersensitive sites
      (RHS4-7). Among these, RHS7 seems to have the strongest impact on TH 2
      differentiation. We investigated whether within the human homolog of RHS7,
      functional polymorphisms exist, which could affect DNA methylation or gene
      expression in the 5q31 locus and might have an influence on asthma status or IgE
      regulation. METHODS: The human RHS7 region was fine mapped using 1000 genomes
      database information. In silico analysis and electrophoretic mobility shift
      assays were used to assess SNP function. Allele-specific effects on DNA
      methylation were evaluated in cord blood (n = 73) and at age of 4.5 years (n =
      61) by pyrosequencing. Allele-specific effects on RAD50, IL4, and IL13 expression
      were analyzed in 100 subjects. Associations with asthma and IgE levels were
      investigated in the MAGICS/ISAAC II population (n = 1145). RESULTS: Polymorphism
      rs2240032 in the RHS7 region is suggestive of allele-specific transcription
      factor binding, affects methylation of the IL13 promoter region and influences
      RAD50 and IL4 expression (lowest P = 0.0027). It is also associated with total
      serum IgE levels (P = 0.0227). CONCLUSION: A functional relevant polymorphism in
      the TH 2 locus control region, equivalent to RHS7 in mice, affects DNA
      methylation and gene expression within 5q31 and influences total serum IgE on the
      population level.

PMID- 24866381
TI  - Particulate PAH emissions from residential biomass combustion: time-resolved
      analysis with aerosol mass spectrometry.
AB  - Time-resolved emissions of particulate polycyclic aromatic hydrocarbons (PAHs)
      and total organic particulate matter (OA) from a wood log stove and an adjusted
      pellet stove were investigated with high-resolution time-of-flight aerosol mass
      spectrometry (AMS). The highest OA emissions were found during the addition of
      log wood on glowing embers, that is, slow burning pyrolysis conditions. These
      emissions contained about 1% PAHs (of OA). The highest PAH emissions were found
      during fast burning under hot air starved combustion conditions, in both stoves.
      In the latter case, PAHs contributed up to 40% of OA, likely due to thermal
      degradation of other condensable species. The distribution of PAHs was also
      shifted toward larger molecules in these emissions. AMS signals attributed to
      PAHs were found at molecular weights up to 600 Da. The vacuum aerodynamic size
      distribution was found to be bimodal with a smaller mode (Dva ~ 200 nm)
      dominating under hot air starved combustion and a larger sized mode dominating
      under slow burning pyrolysis (Dva ~ 600 nm). Simultaneous reduction of PAHs, OA
      and total particulate matter from residential biomass combustion may prove to be
      a challenge for environmental legislation efforts as these classes of emissions
      are elevated at different combustion conditions. 

PMID- 24866382
TI  - Induction of T helper 2 responses against human apolipoprotein B100 does not
      affect atherosclerosis in ApoE-/- mice.
AB  - AIMS: Immune responses against LDL antigens have been found to play an important
      modulatory role in atherosclerosis. Immunization with homologous oxidized LDL, as
      well as human apolipoprotein B100 (ApoB)-derived peptides, inhibits
      atherosclerosis in hypercholesterolaemic animal models of atherosclerosis.
      However, the role of antigen-specific T helper 2 (Th2) responses in
      atherosclerosis remains to be fully clarified. METHODS AND RESULTS: ApoE(-/-)
      mice on high-fat diet were immunized with human ApoB using Alum as an adjuvant at
      12, 14, and 16 weeks of age. Alum-injected and non-treated mice were used as
      controls. At 17 weeks of age, a matrigel plug containing ApoB was placed
      subcutaneously and T-cell infiltration into the plug as well as the development
      of aortic root atherosclerotic lesions were analysed after an additional 7 days.
      Immunization with ApoB resulted in four-fold increased accumulation of effector T
      cells in ApoB-containing matrigel when compared with control groups. The levels
      of the Th2 cytokines IL-4, IL-5, and IL-10 were also increased in ApoB-containing
      matrigel plugs. Moreover, the levels of Th2-associated IgG1 against human and
      also mouse LDL were increased in the plasma of ApoB-immunized mice. In spite of
      the induction of a Th2 response partially reacting also with the endogenous LDL,
      there was no difference in atherosclerosis when compared with the Alum group.
      CONCLUSIONS: This study describes a novel model to study antigen-specific T-cell
      responses in vivo in mouse models of atherosclerosis. The results suggest that
      activation of Th2 immunity does not mediate the protective effect of immunization
      with LDL antigens described previously.

PMID- 24866384
TI  - Frizzled7 controls vascular permeability through the Wnt-canonical pathway and
      cross-talk with endothelial cell junction complexes.
AB  - AIMS: Vascular permeability is essential for the health of normal tissues and is
      an important characteristic of many disease states. The role of the Wnt/frizzled
      pathway in vascular biology has recently been reported. The objectives of this
      study are to analyse the role of Frizzled7 (Fzd7) receptor in the control of
      vascular integrity. METHODS AND RESULTS: Fzd7 is expressed in endothelial cells
      and accumulates at the points of cell-cell contact in association with VE
      cadherin and beta-catenin, two major adherens junction molecules. To selectively
      delete fzd7 in the vasculature, we developed gene targeting approaches using
      CreLox strategy in mice. Genetic fzd7 inhibition in the endothelium increases
      vascular permeability in basal and factor-induced conditions. On the cellular
      level, fzd7 knockdown or depletion leads to an increase in paracellular
      permeability with a loss of adherens junction organization. These impairments are
      associated with a decrease in both VE-Cadherin and beta-catenin expression, a
      decrease in their association and an increase of tyrosine phosphorylation of VE
      cadherin/beta-catenin. Fzd7 transduces a Wnt/beta-catenin signalling cascade that
      is required to regulate beta-catenin and canonical target gene expression.
      Finally, LiCl, a GSK3 inhibitor, and beta-catenin overexpression rescued
      endothelial integrity and adherens junction organization, induced by fzd7
      deletion. CONCLUSION: These findings establish that Fzd7 is a new partner of
      adherens junctional complex and represents a novel molecular switch for the
      control of vascular permeability via activation of the Wnt-canonical pathway.

PMID- 24866383
TI  - NEXN inhibits GATA4 and leads to atrial septal defects in mice and humans.
AB  - AIMS: Cardiac structural genes have been implicated as causative factors for
      congenital heart diseases (CHDs). NEXN is an F-actin binding protein and
      previously identified as a disease gene causing cardiomyopathies. Whether NEXN
      contributes to CHDs aetiologically remains unknown. Here, we explored the
      function of NEXN in cardiac development. METHODS AND RESULTS: First, we determine
      the role of NEXN in cardiac differentiation using mouse P19cl6 in vitro model; we
      demonstrated that NEXN inhibited cardiac contractile markers, serving as a
      negative regulator. Interestingly, we found this effect was mediated by GATA4, a
      crucial transcription factor that controls cardiac development by knockdown,
      overexpression, and rescue experiment, respectively. We then generated transgenic
      mouse models and surprisingly, we discovered cardiac-selective expression of the
      NEXN gene caused atrial septal defects (ASDs). Next, to search for the mutations
      in NEXN gene in patients suffering from ASDs, we sequenced the exon and exon
      intron joint regions of the NEXN gene in 150 probands with isolated ASDs and
      identified three mutations in the conserved region of NEXN (c.-52-78C>A, K199E,
      and L227S), which were not found in 500 healthy controls. Finally, we
      characterize the related mechanisms and found all mutations inhibited GATA4
      expression. CONCLUSION: We identify NEXN as a novel gene for ASD and its function
      to inhibit GATA4 established a critical regulation of an F-actin binding protein
      on a transcription factor in cardiac development.

PMID- 24866385
TI  - An investigation into false-negative transthoracic fine needle aspiration and
      core biopsy specimens.
AB  - Transthoracic fine needle aspiration (TFNA)/core needle biopsy (CNB) under
      computed tomography (CT) guidance has proved useful in the assessment of
      pulmonary nodules. We sought to determine the TFNA false-negative (FN) rate at
      our institution and identify potential causes of FN diagnoses. Medical records
      were reviewed from 1,043 consecutive patients who underwent CT-guided TFNA with
      or without CNB of lung nodules over a 5-year time period (2003-2007). Thirty
      seven FN cases of "negative" TFNA/CNB with malignant outcome were identified with
      36 cases available for review, of which 35 had a corresponding CNB. Cases were
      reviewed independently (blinded to original diagnosis) by three pathologists with
      15 age- and sex-matched positive and negative controls. Diagnosis (i.e.,
      nondiagnostic, negative or positive for malignancy, atypical or suspicious) and
      qualitative assessments were recorded. Consensus diagnosis was suspicious or
      positive in 10 (28%) of 36 TFNA cases and suspicious in 1 (3%) of 35 CNB cases,
      indicating potential interpretive errors. Of the 11 interpretive errors
      (including both suspicious and positive cases), 8 were adenocarcinomas, 1
      squamous cell carcinoma, 1 metastatic renal cell carcinoma, and 1 lymphoma. The
      remaining 25 FN cases (69.4%) were considered sampling errors and consisted of 7
      adenocarcinomas, 3 nonsmall cell carcinomas, 3 lymphomas, 2 squamous cell
      carcinomas, and 2 renal cell carcinomas. Interpretive and sampling error cases
      were more likely to abut the pleura, while histopathologically, they tended to be
      necrotic and air-dried. The overall FN rate in this patient cohort is 3.5% (1.1%
      interpretive and 2.4% sampling errors).

PMID- 24866387
TI  - Hybrid treatment of an isthmic aneurysm and subclavian ectasia after successful
      recoarctation repair with ventral aorta.

PMID- 24866386
TI  - Syk/Src-targeted anti-inflammatory activity of Codariocalyx motorius ethanolic
      extract.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Codariocalyx motorius (Houtt.) H. Ohashi
      (Fabaceae) is one of several ethnopharmacologically valuable South Asian species
      prescribed as an herbal medicine for various inflammatory diseases. Due to the
      lack of systematic studies on this plant, we aimed to explore the inhibitory
      activity of Codariocalyx motorius toward inflammatory responses using its
      ethanolic extract (Cm-EE). MATERIALS AND METHODS: Lipopolysaccharide (LPS)
      treated macrophages and a HCl/EtOH-induced gastritis model were used for
      evaluation of the anti-inflammatory activity of Cm-EE. HPLC and spectroscopic
      analysis were employed to identify potential active components. Mechanistic
      approaches to determine target enzymes included kinase assays, reporter gene
      assays, and overexpression of target enzymes. RESULTS: Cm-EE strongly suppressed
      nitric oxide (NO) and prostaglandin E2 (PGE2) release. Cm-EE-mediated inhibition
      was observed at the transcriptional level in the form of suppression of NF-kappaB
      (p65) translocation and activation. This extract also lowered the levels of
      phosphorylation of Src and Syk, their kinase activity, and their formation of
      signalling complexes by binding to the downstream enzyme p85/PI3K. In accord with
      these findings, the phosphorylation of p85 induced by overexpression of Src or
      Syk was also diminished by Cm-EE. Orally administered Cm-EE clearly inhibited
      gastritic ulcer formation and the phosphorylation of IkappaBalpha and Src in
      HCl/EtOH-treated stomachs of mice. By phytochemical analysis, luteolin and its
      glycoside, apigenin-7-O-glucuronide, and scutellarein-6-O-glucuronide were
      identified as major components of Cm-EE. Among these, it was found that luteolin
      was able to strongly suppress NO and PGE2 production under the same conditions.
      CONCLUSION: Syk/Src-targeted inhibition of NF-kappaB by Cm-EE could be a major
      anti-inflammatory mechanism contributing to its ethno pharmacological role as an
      anti-inflammatory herbal medicine.

PMID- 24866388
TI  - Results of one-and-a-half-patch technique for repair of complete atrioventricular
      septal defect with a large ventricular component.
AB  - OBJECTIVES: Management of complete atrioventricular (AV) septal defect (CAVSD)
      with a large ventricular component (>1 cm) remains controversial. The purpose of
      this study was to assess the feasibility of the one-and-a-half patch technique in
      repairing this lesion. METHODS: This was a retrospective review of patients
      undergoing surgical repair of CAVSD with a large ventricular component (>1 cm).
      Of the 51 patients who were identified in our database (2005-13), 18 underwent
      the two-patch repair, 12 underwent the modified single-patch repair and 21
      underwent the one-and-a-half-patch repair. The CAVSD was combined with tetralogy
      of Fallot (TOF) in 3 patients and with double-outlet right ventricle (DORV) and
      pulmonary stenosis (PS) in two individuals in the one-and-a-half-patch group.
      RESULTS: There were two hospital deaths in the two-patch group, but no deaths in
      the other two groups. The modified single-patch procedure was associated with the
      shortest myocardial ischaemic and cardiopulmonary bypass (CPB) times, the two
      patch procedure was associated with the longest times and the 1.5-patch procedure
      times were intermediate. Median follow-up was 35 months (41.6 +/- 27.2 months).
      There were no reoperations in the 1.5-patch group while reintervention was
      required for 1 patient in the two-patch group (P = 0.252) and 3 patients in the
      modified single-patch group (P = 0.017). The function of the reconstituted AV
      valves improved after operation in the 1.5-patch group. No patient in these three
      groups developed subsequent left ventricular outflow tract obstruction.
      CONCLUSIONS: The 1.5-patch technique is an attractive clinical option. It
      produces acceptable mid-term results comparable with two conventional techniques
      in patients with similarly sized ventricular component.

PMID- 24866390
TI  - Transparency in reimbursement decisions: in whose best interest?

PMID- 24866389
TI  - Blood feeding and Plasmodium infection alters the miRNome of Anopheles stephensi.
AB  - Blood feeding is an integral process required for physiological functions and
      propagation of the malaria vector Anopheles. During blood feeding, presence of
      the malaria parasite, Plasmodium in the blood induces several host effector
      molecules including microRNAs which play important roles in the development and
      maturation of the parasite within the mosquito. The present study was undertaken
      to elucidate the dynamic expression of miRNAs during gonotrophic cycle and
      parasite development in Anopheles stephensi. Using next generation sequencing
      technology, we identified 126 miRNAs of which 17 were novel miRNAs. The miRNAs
      were further validated by northern hybridization and cloning. Blood feeding and
      parasitized blood feeding in the mosquitoes revealed regulation of 13 and 16
      miRNAs respectively. Expression profiling of these miRNAs revealed that
      significant miRNAs were down-regulated upon parasitized blood feeding with a
      repertoire of miRNAs showing stage specific up-regulation. Expression profiles of
      significantly modulated miRNAs were further validated by real time PCR. Target
      prediction of regulated miRNAs revealed overlapping targeting by different
      miRNAs. These targets included several metabolic pathways including metabolic,
      redox homeostasis and protein processing machinery components. Our analysis
      revealed tight regulation of specific miRNAs post blood feeding and parasite
      infection in An. stephensi. Such regulated expression suggests possible role of
      these miRNAs during gonotrophic cycle in mosquito. Another set of miRNAs were
      also significantly regulated at 42 h and 5 days post infection indicating
      parasite stage-specific role of host miRNAs. This study will result in better
      understanding of the role of miRNAs during gonotrophic cycle and parasite
      development in mosquito and can probably facilitate in devising novel malaria
      control strategies at vector level. 

PMID- 24866393
TI  - Hand-held dynamometry fixated with a tripod is reliable for assessment of back
      extensor strength in women with osteoporosis.
AB  - An appropriate method to assess back extensor strength in clinical practice has
      not yet been described. Our results showed that a hand-held dynamometry fixated
      with a tripod is reliable for assessing back extensor strength in women with
      osteoporosis. INTRODUCTION: Back strengthening exercises play an important role
      in the rehabilitation of patients with osteoporotic vertebral fractures.
      Evaluation of the effect of back strengthening exercises requires a method
      suitable for use in clinical practice to measure back extensor strength. A hand
      held dynamometer (HHD) is quick and easy to handle in clinical practice.
      Currently, there is a lack of evidence whether a HHD is reliable for assessment
      of back extensor strength in people with osteoporosis. When using a HHD, it may
      be difficult for the tester to provide a counter pressure corresponding to the
      effort of the patient. In order to accommodate this, we have developed a tripod
      and a belt system, which was used to fixate the HHD. This study examined the
      intra-tester reliability of back extensor strength assessment in women with
      osteoporosis using a HHD. METHODS: Back extensor strength of the participants was
      measured on two events with 7-day intervals. Test procedures were standardized,
      and all tests were performed by the same tester. RESULTS: Forty-eight women with
      osteoporosis and vertebral fractures were included in the analysis. The
      coefficient of variation was 22% using a HHD fixated by the tester and 17% using
      a HHD fixated with the tripod. ICC was 0.75 (95% confidence interval (CI), 0.63
      and 0.88) when using a HHD with fixated by the tester and 0.90 (95% CI, 0.84 and
      0.95) when using a HHD fixated with the tripod. CONCLUSION: A HHD fixated with a
      tripod is reliable for the assessment of back extensor strength in women with
      osteoporosis and vertebral fractures.

PMID- 24866391
TI  - Enhanced oxygen-tolerance of the full heterotrimeric membrane-bound [NiFe]
      hydrogenase of Ralstonia eutropha.
AB  - Hydrogenases are oxygen-sensitive enzymes that catalyze the conversion between
      protons and hydrogen. Water-soluble subcomplexes of membrane-bound [NiFe]
      hydrogenases (MBH) have been extensively studied for applications in hydrogen
      oxygen fuel cells as they are relatively tolerant to oxygen, although even these
      catalysts are still inactivated in oxidative conditions. Here, the full
      heterotrimeric MBH of Ralstonia eutropha, including the membrane-integral
      cytochrome b subunit, was investigated electrochemically using electrodes
      modified with planar tethered bilayer lipid membranes (tBLM). Cyclic voltammetry
      and chronoamperometry experiments show that MBH, in equilibrium with the quinone
      pool in the tBLM, does not anaerobically inactivate under oxidative redox
      conditions. In aerobic environments, the MBH is reversibly inactivated by O2, but
      reactivation was found to be fast even under oxidative redox conditions. This
      enhanced resistance to inactivation is ascribed to the oligomeric state of MBH in
      the lipid membrane. 

PMID- 24866395
TI  - A novel panel of microRNAs provides a sensitive and specific tool for the
      diagnosis of breast cancer.
AB  - Breast cancer has a high fatality rate. Early diagnosis reduces the rate of
      mortality; therefore, novel diagnostic methods are urgently required. The present
      study investigated the correlation of serum microRNA (miRNA/miR) expression with
      breast cancer, and tested a panel of miRNAs as promising potential biomarkers for
      breast cancer. Six miRNAs (miR-374, miR-666-5p, miR-451, miR-148a, miR-27a and
      miR-30b) were selected for analysis and their differential expression levels were
      quantified using qPCR. The results demonstrated that four out of the six
      candidate miRNAs were significantly downregulated in breast cancer patients (miR
      451, P=0.000; miR-148a, P=0.021; miR-27a, P=0.013 and miR-30b, P=0.001). A panel
      of miRNAs consisting of the four downregulated miRNAs was able to distinguish
      breast cancer from healthy controls, with an area under the receiver operating
      characteristic curve of 95.3%, a sensitivity of 94.7% and a specificity of 82.8%.
      Thus, this panel of miRNAs may be used as a sensitive and specific tool for the
      diagnosis of breast cancer. 

PMID- 24866394
TI  - The assessment of bone mineral content and density of the lumbar spine and
      proximal femur in US submariners.
AB  - The submarine environment is unique in that there is limited space and no
      sunlight, which may negatively affect skeletal health and lead to accelerated
      bone loss, osteoporosis, and fractures. INTRODUCTION: The primary purpose of this
      study was to determine whether there was an association with submarine service,
      specifically time spent at sea, and bone mineral content (BMC) and bone mineral
      density (BMD) of the lumbar spine and dual proximal femur (total hip and femoral
      neck) measured by DXA. METHODS: This is a cross-sectional study of 462
      submariners 20-91 years old. Variables included in the analysis were age, height,
      race, alcohol intake, tobacco use, fracture history, conditions, and medications
      known to cause bone loss and osteoporosis and submarine service. RESULTS: Of the
      submarine service predictors, only serving onboard a diesel submarine was
      determined to be independently associated with a reduction in BMD of the total
      hip and femur neck, while no submarine service predictor increased the odds of
      having low BMD. In submariners 50+ years old, the age-adjusted prevalence of
      osteopenia was 15.7 % (lumbar spine) and 40.4 % (femur neck), while the
      prevalence of osteoporosis was 4.8 % (lumbar spine) and 4.2 % (femur neck), rates
      that did not differ from NHANES 2005-2008. In submariners <50 years old, 3.1 %
      was below the expected range for age. The proportion of submariners 50+ years old
      that met the FRAX criteria for pharmacological treatment was 12 %. CONCLUSIONS:
      Intermittent periods of submergence that can range from a few days to 3+ months
      do not appear to compromise skeletal health differently than the general
      population.

PMID- 24866396
TI  - Novel acoustic stimuli can alter locomotor speed to hippocampal theta
      relationship.
AB  - Hippocampal theta (6-12 Hz) plays a critical role in synchronizing the discharge
      of action potentials, ultimately orchestrating individual neurons into large
      scale ensembles. Alterations in theta dynamics may reflect variations in
      sensorimotor integration, the flow of sensory input, and/or cognitive processing.
      Previously we have investigated septotemporal variation in the locomotor speed to
      theta amplitude relationship as well as how that relationship is systematically
      altered as a function of novel, physical space. In the present study, we ask,
      beyond physical space, whether persistent and passive sound delivery can alter
      septal theta local field potential rhythm dynamics. Results indicate pronounced
      alterations in the slope of the speed to theta amplitude relationship as a
      function of sound presentation and location. Further, this reduction in slope
      habituates across days. The current findings highlight that moment-to-moment
      alterations in theta amplitude is a rich dynamic index that is quantitatively
      related to both alterations in motor behavior and sensory experience. The
      implications of these phenomena are discussed with respect to emergent cognitive
      functions subserved by hippocampal circuits.

PMID- 24866397
TI  - Short communication: HIV-1 Nef protein carries multiple epitopes suitable for
      induction of cellular immunity for an HIV vaccine in Africa.
AB  - Using the early protein HIV Nef, new HLA class I binding epitopes of importance
      for immune responses to HIV were predicted for common African alleles. In total
      we identified 45 epitopes previously not described for the HLA alleles A*30:01,
      A*30:02, B*58:01, and C*07:01 and compared them to reported epitopes, primarily
      from HLA-A*02:01, from the Los Alamos database and our own vaccine studies.
      Related to its small size, the Nef gene/protein appears to be able to contribute
      effectively to confer both stronger and broader cellular immunogenicity to an HIV
      1 vaccine. We also propose feasible mutations of such an additional vaccine
      antigen to preserve its immunogenicity, modified not to confer HLA or CD4(+) down
      regulating activities. This article includes data on a valuable HIV immunogenic
      component for a vaccine in Africa.

PMID- 24866399
TI  - Beryllium dimer: a bond based on non-dynamical correlation.
AB  - The bond nature in beryllium dimer has been theoretically investigated using high
      level ab initio methods. A series of ANO basis sets of increasing quality, going
      from sp to spdf ghi contractions, has been employed, combined with HF, CAS-SCF,
      CISD, and MRCI calculations with several different active spaces. The quality of
      these calculations has been checked by comparing the results with valence Full-CI
      calculations, performed with the same basis sets. It is shown that two quasi
      degenerated partly occupied orbitals play a crucial role to give a qualitatively
      correct description of the bond. Their nature is similar to that of the edge
      orbitals that give rise to the quasi-degenerated singlet-triplet states in longer
      beryllium chains.

PMID- 24866398
TI  - Charge-conversional and pH-sensitive PEGylated polymeric micelles as efficient
      nanocarriers for drug delivery.
AB  - A novel amphiphilic copolymer, poly (ethylene glycol)-graft
      polyethyleneimine/amide (PEG-g-PEI/amide), is synthesized by grafting PEG and1,2
      cis-Cyclohexanedicarboxylic anhydride onto the PEI. PEGylated polymeric micelles
      can be assembled from the amphiphilic copolymers with well-defined nano-sizes,
      and anti-cancer drugs are successfully loaded into micelle core formed by the
      amide. The amides with neighboring carboxylic acid groups exhibit pH-dependent
      hydrolysis and can reversibly shield the cationic charge of amine groups on the
      PEI, giving the micelles a charge-conversion property from negative to positive
      in acidic tumor tissue environment. Meanwhile, the cleavage of amide bonds at
      acidic pH also results in the disassembly of the micelle and pH-responsive drug
      release. These micelles are promising drug delivery systems due to their smart
      properties: PEGylation, suitable size, charge-conversion, and simultaneous pH
      sensitive drug release. 

PMID- 24866400
TI  - Prevalence and correlates of depressive symptoms in a catchment-area based cohort
      of older community-living schizophrenia patients.
AB  - BACKGROUND: Depressive symptoms frequently accompany schizophrenia. Older
      patients constitute the fastest growing segment of the schizophrenia population.
      With regard to the risk factors associated with depression, it is uncertain to
      which extent older schizophrenia patients differ from their age peers in the
      community. METHODS: We assessed self-reported depressive symptoms in an
      epidemiological sample of older Dutch community-living patients with
      schizophrenia or schizoaffective disorder (N=99; mean age 67years). Demographic,
      clinical and social variables were evaluated for their predictive value on the
      level of depressive symptoms. A comparison group, proportionally matched for age
      and gender, was recruited from a community study. RESULTS: In the schizophrenia
      group, 47.5% reported depressive symptoms at a level indicating clinically
      relevant depression, in contrast to 12.1% in their age peers (odds ratio 6.55;
      95% CI, 3.19-13.48; p<0.001). This difference could not be explained by
      differential exposure to the evaluated general risk factors. In both groups,
      functional limitations were the strongest predictor of depressive symptoms. In
      the patient group, chronic physical disorders and lack of a confidant were
      predictors, while a diagnosis of schizoaffective disorder (vs. schizophrenia) was
      the only disorder-related risk factor that contributed to depressive symptoms,
      with marginal significance. CONCLUSION: The high rate of depressive symptoms in
      this epidemiological sample of older schizophrenia patients confirms that these
      symptoms frequently accompany this severe mental illness in late life. With
      physical and social factors as important predictors of depressive symptoms, risk
      factors for depression are more comparable between older schizophrenia patients
      and their age peers than is often assumed.

PMID- 24866402
TI  - Investigation of TREM2, PLD3, and UNC5C variants in patients with Alzheimer's
      disease from mainland China.
AB  - Recently, 3 rare coding variants significantly associated with Alzheimer's
      disease (AD) risk have been identified in western populations using whole exome
      sequencing method, including p.R47H in TREM2, p.V232M in PLD3, and p.T835M in
      UNC5C. To examine whether these variants are genetic risk factors in patients
      with AD from mainland China, we sequenced exon 2 of TREM2, exon 9 of PLD3, and
      exon 15 of UNC5C in Chinese Han population including 360 patients with AD and 400
      control individuals. As a result, none of these 3 variants were identified in all
      subjects, however, 1 novel variant (p.A130V) in TREM2 and 4 novel variants
      (p.Q860H, p.T837K, p.S843G, and p.V836V) in UNC5C were detected in unrelated
      patients with late-onset AD. These findings suggest the 3 rare coding variants
      might not play an important role in AD risk in mainland China. 

PMID- 24866401
TI  - Ataxin-2 as potential disease modifier in C9ORF72 expansion carriers.
AB  - Repeat expansions in chromosome 9 open reading frame 72 (C9ORF72) are an
      important cause of both motor neuron disease (MND) and frontotemporal dementia
      (FTD). Currently, little is known about factors that could account for the
      phenotypic heterogeneity detected in C9ORF72 expansion carriers. In this study,
      we investigated 4 genes that could represent genetic modifiers: ataxin-2 (ATXN2),
      non-imprinted in Prader-Willi/Angelman syndrome 1 (NIPA1), survival motor neuron
      1 (SMN1), and survival motor neuron 2 (SMN2). Assessment of these genes, in a
      unique cohort of 331 C9ORF72 expansion carriers and 376 control subjects,
      revealed that intermediate repeat lengths in ATXN2 possibly act as disease
      modifier in C9ORF72 expansion carriers; no evidence was provided for a potential
      role of NIPA1, SMN1, or SMN2. The effects of intermediate ATXN2 repeats were most
      profound in probands with MND or FTD/MND (2.1% vs. 0% in control subjects, p =
      0.013), whereas the frequency in probands with FTD was identical to control
      subjects. Though intermediate ATXN2 repeats were already known to be associated
      with MND risk, previous reports did not focus on individuals with clear
      pathogenic mutations, such as repeat expansions in C9ORF72. Based on our present
      findings, we postulate that intermediate ATXN2 repeat lengths may render C9ORF72
      expansion carriers more susceptible to the development of MND; further studies
      are needed, however, to validate our findings.

PMID- 24866403
TI  - Histone deacetylase 6 regulates cytotoxic alpha-synuclein accumulation through
      induction of the heat shock response.
AB  - Abnormal aggregation of alpha-synuclein (alpha-syn) is central to the
      pathogenesis of Parkinson's disease (PD). Histone deacetylase 6 (HDAC6) was
      previously shown to control major cell response pathways to the cytotoxic
      ubiquitinated aggregates in some protein aggregation diseases. Whether it
      influences the aggregation process of alpha-syn in PD models and its related
      mechanisms are not completely known. Here, we characterized the expression and
      function of HDAC6 in the ubiquitin-proteasome system impairment-induced PD model.
      Our results showed that HDAC6 inhibition further exacerbated the nigrostriatal
      dopamine neurodegeneration and upregulated alpha-syn oligomers levels, whereas
      HDAC6 overexpression in vitro showed the opposite effects. More importantly, we
      provided evidence for the first time that HDAC6 regulating alpha-syn oligomers
      levels were related to its ability to trigger the heat shock response in a heat
      shock protein 90-dependent manner. HDAC6 mediated the dissociation of heat shock
      protein 90-heat shock factor 1-containing complex, and the activation of heat
      shock factor 1, which led to the expression of major molecular chaperones to
      prevent the deleterious alpha-syn aggregation. Thus, we propose that HDAC6
      appears as a key modulator of cell protective response to the cytotoxic alpha-syn
      aggregates and may serve as a potential target for therapy development in PD.

PMID- 24866405
TI  - Characterization of yeast mutants lacking alkaline ceramidases YPC1 and YDC1.
AB  - Humans and yeast possess alkaline ceramidases located in the early secretory
      pathway. Single deletions of the highly homologous yeast alkaline ceramidases
      YPC1 and YDC1 have very little genetic interactions or phenotypes. Here, we
      performed chemical-genetic screens to find deletions/conditions that would alter
      the growth of ypc1?ydc1? double mutants. These screens were essentially negative,
      demonstrating that ceramidase activity is not required for cell growth even under
      genetic stresses. A previously reported protein targeting defect of ypc1? could
      not be reproduced and reported abnormalities in sphingolipid biosynthesis
      detected by metabolic labeling do not alter the mass spectrometric lipid profile
      of ypc1?ydc1? cells. Ceramides of ypc1?ydc1? remained normal even in presence of
      aureobasidin A, an inhibitor of inositolphosphorylceramide synthase. Moreover, in
      caloric restriction conditions Ypc1p reduces chronological life span. A novel
      finding is that, when working backwards as a ceramide synthase in vivo, Ypc1p
      prefers C24 and C26 fatty acids as substrates, whereas it prefers C16:0, when
      solubilized in detergent and working in vitro. Therefore, its physiological
      activity may not only concern the minor ceramides containing C14 and C16.
      Intriguingly, so far the sole discernable benefit of conserving YPC1 for yeast
      resides with its ability to convey relative resistance toward H2O2.

PMID- 24866406
TI  - Inhibition of N-myc downstream-regulated gene-2 is involved in an astrocyte
      specific neuroprotection induced by sevoflurane preconditioning.
AB  - BACKGROUND: Mechanism of sevoflurane preconditioning-induced cerebral ischemic
      tolerance is unclear. This study investigates the role of N-myc downstream
      regulated gene-2 (NDRG2) in the neuroprotection of sevoflurane preconditioning in
      ischemic model both in vivo and in vitro. METHODS: At 2 h after sevoflurane (2%)
      preconditioning for 1 h, rats were subjected to middle cerebral artery occlusion
      for 120 min. Neurobehavioral scores (n = 10), infarct volumes (n = 10), cellular
      apoptosis (n = 6), and NDRG2 expression (n = 6) were determined at 24 h after
      reperfusion. In vitro, cultural astrocytes were exposed to oxygen-glucose
      deprivation for 4 h. Cellular viability, cytotoxicity, apoptosis, and NDRG2
      expression (n = 6) were evaluated in the presence or absence of NDRG2-specific
      small interfering RNA or NDRG2 overexpression plasmid. RESULTS: Sevoflurane
      preconditioning decreased apoptosis (terminal deoxynucleotidyl transferase
      mediated 2'-deoxyuridine 5'-triphosphate nick-end labeling-positive cells reduced
      to 31.2 +/- 5.3% and cleaved Caspase-3 reduced to 1.42 +/- 0.21 fold) and
      inhibited NDRG2 expression (1.28 +/- 0.15 fold) and nuclear translocation (2.21
      +/- 0.29 fold) in ischemic penumbra. Similar effects were observed in cultural
      astrocytes exposed to oxygen-glucose deprivation. NDRG2 knockdown by small
      interfering RNA attenuated oxygen-glucose deprivation-induced injury (cell
      viability increased to 80.5 +/- 4.1%; lactate dehydrogenase release reduced to
      30.5 +/- 4.0%) and cellular apoptosis (cleaved Caspase-3 reduced to 1.55 +/- 0.21
      fold; terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'
      triphosphate nick-end labeling-positive cells reduced to 18.2 +/- 4.3%), whereas
      NDRG2 overexpression reversed the protective effects of sevoflurane
      preconditioning. All the data are presented as mean +/- SD. CONCLUSION:
      Sevoflurane preconditioning inhibits NDRG2 up-regulation and nuclear
      translocation in astrocytes to induce cerebral ischemic tolerance via
      antiapoptosis, which represents one new mechanism of sevoflurane preconditioning
      and provides a novel target for neuroprotection.

PMID- 24866404
TI  - White matter integrity is associated with cerebrospinal fluid markers of
      Alzheimer's disease in normal adults.
AB  - We explored whether white matter (WM) integrity in cognitively normal (CN) older
      adults is associated with cerebrospinal fluid (CSF) markers of Alzheimer's
      disease pathology. Twenty CN older adults underwent lumbar puncture and magnetic
      resonance imaging within a few days of each other. Analysis of diffusion tensor
      imaging data involved a priori region of interest and voxelwise approaches. The
      region of interest results revealed a positive correlation between CSF measures
      of amyloid-beta (Abeta(42) and Abeta(42)/p-Tau(181)) and WM integrity in the
      fornix, a relationship which persisted after controlling for hippocampal volume
      and fornix volume. Lower WM integrity in the same portion of the fornix was also
      associated with reduced performance on the Digit Symbol test. Subsequent
      exploratory voxelwise analyses indicated a positive correlation between CSF
      Abeta(42)/p-Tau(181) and WM integrity in bilateral portions of the fornix,
      superior longitudinal fasciculus, inferior fronto-occipital fasciculus, and in
      the corpus callosum and left inferior longitudinal fasciculus. Our results link
      lower WM microstructural integrity in CN older adults with CSF biomarkers of
      Alzheimer's disease and suggest that this association in the fornix may be
      independent of volumetric measures.

PMID- 24866407
TI  - Fibrinogen concentrate does not suppress endogenous fibrinogen synthesis in a 24
      hour porcine trauma model.
AB  - BACKGROUND: Fibrinogen concentrate may reduce blood loss after trauma. However,
      its effect on endogenous fibrinogen synthesis is unknown. The authors
      investigated the effect of exogenous human fibrinogen on endogenous fibrinogen
      metabolism in a 24-h porcine trauma model. METHODS: Coagulopathy was induced in
      20 German Landrace pigs by hemodilution and blunt liver injury. Animals were
      randomized to receive fibrinogen concentrate (100 mg/kg; infusion beginning 20
      min postinjury and lasting approximately 10 min) or saline. Fibrinogen
      concentration, thromboelastometry, and quantitative reverse transcriptase
      polymerase chain reaction of fibrinogen genes in liver tissue samples were
      recorded. Internal organs were examined histologically for emboli. RESULTS:
      Coagulation parameters were impaired and plasma fibrinogen concentrations were
      reduced before starting infusion of fibrinogen concentrate/saline. Twenty minutes
      after starting infusion, exogenous fibrinogen supplementation had increased
      plasma fibrinogen concentration versus controls (171 +/- 19 vs. 63 +/- 10 mg/dl
      [mean +/- SD for Multifibren U]; 185 +/- 30 vs. 41 +/- 4 mg/dl [Thrombin
      reagent]; P < 0.05 for both comparisons). The between-group difference in plasma
      fibrinogen concentration diminished thereafter, with maximum concentrations in
      both groups observed at approximately 24 h, that is, during the acute-phase
      reaction after trauma. Fibrinogen supplementation did not down-regulate
      endogenous fibrinogen synthesis (no between-group differences in fibrinogen
      messenger RNA). Total postinjury blood loss was significantly lower in the
      fibrinogen group (1,062 +/- 216 vs. 1,643 +/- 244 ml; P < 0.001). No signs of
      thromboembolism were observed. CONCLUSIONS: Administration of human fibrinogen
      concentrate did not down-regulate endogenous porcine fibrinogen synthesis. The
      effect on plasma fibrinogen concentration was most pronounced at 20 min but
      nonsignificant at approximately 24 h.

PMID- 24866411
TI  - Glaucoma drainage device exposure in Asian eyes.

PMID- 24866413
TI  - Evidence of multi-step nucleation leading to various crystallization pathways
      from an Fe-O-Al melt.
AB  - The crystallization process from a solution begins with nucleation, which
      determines the structure and size of the resulting crystals. Further
      understanding of multi-pathway crystallizations from solution through two-step
      nucleation mechanisms is needed. This study uses density functional theory to
      probe the thermodynamic properties of alumina clusters at high temperature and
      reveals the thermodynamic relationship between these clusters and the saturation
      levels of dissolved oxygen and aluminum in an Fe-O-Al melt. Based on the
      thermodynamics of cluster formation and the experimental evidence for both excess
      oxygen in the Fe-O-Al melt and for alumina with a polycrystalline structure in
      solidified iron, we demonstrate that the appearance of various types of clusters
      that depends on the saturation ratio determines the nucleation steps that lead to
      the various crystallization pathways. Such mechanisms may also be important in
      nucleation and crystallization from solution. 

PMID- 24866414
TI  - Zinc finger protein 804A (ZNF804A) and verbal deficits in individuals with
      autism.
AB  - BACKGROUND: In a genome-wide association study of autism, zinc finger protein
      804A (ZNF804A) single nucleotide polymorphisms (SNPs) were found to be nominally
      associated in verbally deficient individuals with autism. Zinc finger protein
      804A copy number variations (CNVs) have also been observed in individuals with
      autism. In addition, ZNF804A is known to be involved in theory of mind (ToM)
      tasks, and ToM deficits are deemed responsible for the communication and social
      challenges faced by individuals with autism. We hypothesized that ZNF804A could
      be a risk gene for autism. METHODS: We examined the genetic association and CNVs
      of ZNF804A in 841 families in which 1 or more members had autism. We compared the
      expression of ZNF804A in the postmortem brains of individuals with autism (n = 8)
      and controls (n = 13). We also assessed in vitro the effect of ZNF804A silencing
      on the expression of several genes known to be involved in verbal efficiency and
      social cognition. RESULTS: We found that rs7603001 was nominally associated with
      autism (p = 0.018). The association was stronger (p = 0.008) in the families of
      individuals with autism who were verbally deficient (n = 761 families). We
      observed ZNF804A CNVs in 7 verbally deficient boys with autism. In ZNF804A
      knockdown cells, the expression of synaptosomal-associated protein, 25kDa
      (SNAP25) was reduced compared with controls (p = 0.009). The expression of
      ZNF804A (p = 0.009) and SNAP25 (p = 0.009) were reduced in the anterior cingulate
      gyrus (ACG) of individuals with autism. There was a strong positive correlation
      between the expression of ZNF804A and SNAP25 in the ACG (p < 0.001). LIMITATIONS:
      Study limitations include our small sample size of postmortem brains. CONCLUSION:
      Our results suggest that ZNF804A could be a potential candidate gene mediating
      the intermediate phenotypes associated with verbal traits in individuals with
      autism.

PMID- 24866417
TI  - Wrapping/unwrapping transition of double-stranded DNA in DNA-nanosphere complexes
      induced by multivalent anions.
AB  - Wrapping and unwrapping behaviors of double-stranded DNA around a positively
      charged nanosphere in solution are studied by using the coarse-grained molecular
      dynamics (CGMD) simulation method. When monovalent, divalent and trivalent anions
      are added to the DNA-nanosphere complex solution, double-stranded DNA binds with
      a nanosphere owing to strong electrostatic attraction. However, when tetravalent
      anions are added to the DNA-nanosphere complex solution, local charge inversion
      is observed for a high anion concentration of tetravalent anions and the double
      stranded DNA can be unwrapped from the nanosphere because of the local charge
      inversion near the nanosphere. Moreover, the helical structure of DNA is damaged
      when double-stranded DNA wraps around the nanosphere and the helical structure
      can be rebuilt when the double-stranded DNA unwraps from the nanosphere. This
      study can help us understand how to control the release of DNA in DNA-nanosphere
      complexes. 

PMID- 24866415
TI  - Resting-state functional connectivity abnormalities in patients with obsessive
      compulsive disorder and their healthy first-degree relatives.
AB  - BACKGROUND: Obsessive-compulsive disorder (OCD) is a common, heritable
      neuropsychiatric disorder, hypothetically underpinned by dysfunction of brain
      cortical-striatal-thalamic-cortical (CSTC) circuits; however, the extent of brain
      functional abnormalities in individuals with OCD is unclear, and the genetic
      basis of this disorder is poorly understood. We determined the whole brain
      functional connectivity patterns in patients with OCD and their healthy first
      degree relatives. METHODS: We used resting-state fMRI to measure functional
      connectivity strength in patients with OCD, their healthy first-degree relatives
      and healthy controls. Whole brain functional networks were constructed by
      measuring the temporal correlations of all brain voxel pairs and further analyzed
      using a graph theory approach. RESULTS: We enrolled 39 patients with OCD, 20
      healthy first-degree relatives and 39 healthy controls in our study. Compared
      with healthy controls, patients with OCD showed increased functional connectivity
      primarily within the CSTC circuits and decreased functional connectivity in the
      occipital cortex, temporal cortex and cerebellum. Moreover, patients with OCD and
      their first-degree relatives exhibited overlapping increased functional
      connectivity strength in the bilateral caudate nucleus, left orbitofrontal cortex
      (OFC) and left middle temporal gyrus. LIMITATIONS: Potential confounding factors,
      such as medication use, heterogeneity in symptom clusters and comorbid disorders,
      may have impacted our findings. CONCLUSION: Our preliminary results suggest that
      patients with OCD have abnormal resting-state functional connectivity that is not
      limited to CSTC circuits and involves abnormalities in additional large-scale
      brain systems, especially the limbic system. Moreover, resting-state functional
      connectivity strength abnormalities in the left OFC, bilateral caudate nucleus
      and left middle temporal gyrus may be neuroimaging endophenotypes for OCD.

PMID- 24866416
TI  - Substrate specificity of the lanthipeptide peptidase ElxP and the oxidoreductase
      ElxO.
AB  - The final step in lanthipeptide biosynthesis involves the proteolytic removal of
      an N-terminal leader peptide. In the class I lanthipeptide epilancin 15X, this
      step is performed by the subtilisin-like serine peptidase ElxP. Bioinformatic,
      kinetic, and mass spectrometric analysis revealed that ElxP recognizes the
      stretch of amino acids DLNPQS located near the proteolytic cleavage site of its
      substrate, ElxA. When the ElxP recognition motif was inserted into the noncognate
      lanthipeptide precursor NisA, ElxP was able to proteolytically remove the leader
      peptide from NisA. Proteolytic removal of the leader peptide by ElxP during the
      biosynthesis of epilancin 15X exposes an N-terminal dehydroalanine on the core
      peptide of ElxA that hydrolyzes to a pyruvyl group. The short-chain dehydrogenase
      ElxO reduces the pyruvyl group to a lactyl moiety in the final step of epilancin
      15X maturation. Using synthetic peptides, we also investigated the substrate
      specificity of ElxO and determined the 1.85 A resolution X-ray crystal structure
      of the enzyme. 

PMID- 24866418
TI  - Purification and characterization of parvalbumin isotypes from grass carp
      (Ctenopharyngodon idella).
AB  - The prevalence of fish allergy is rapidly increasing because of a growing fish
      consumption driven mainly by a positive image of the fish and health
      relationship. The purpose of this study was to characterize parvalbumin isotypes
      from grass carp (Ctenopharyngodon idella), one of the most frequently consumed
      freshwater fish in China. Three parvalbumin isotypes were purified using
      consecutive gel filtration and reverse-phase chromatography and denoted as PVI,
      PVII, and PVIII. The molecular weights of the isotypes were determined to be
      11.968, 11.430, and 11.512 kDa, respectively. PVI showed 74% matched amino acids
      sequence with PV isotype 4a from Danio rerio, while PVII and PVIII showed 46%
      matched amino acids sequence with PV isotypes from Hypophthalmichthys molitrix.
      PVII is the dominant allergen, but it was liable to gastrointestinal enzymes as
      PVIII; however, PVI was resistant to pepsin digestion. A further study is to
      characterize the epitopes of PVII, the dominant allergen. 

PMID- 24866420
TI  - Effects of high hydrostatic pressure processing on embryonation of Toxocara canis
      eggs.
AB  - Toxocara canis is a zoonotic nematode parasite that can be transmitted to humans
      by food or water contaminated with T. canis eggs from infected dog feces. High
      pressure processing (HPP) is a useful alternative to thermal treatments to
      eliminate pathogens from foods. Most of the research on HPP has focused on
      prokaryotes, but little is known about its effects on eukaryotic organisms. We
      evaluated the ability of HPP to affect embryonation of T. canis eggs to test the
      hypothesis that HPP treatment can delay development of T. canis eggs. Efficacy of
      HPP was determined by using an embryonation assay on T. canis eggs from naturally
      infected puppies. For each treatment, 2500 T. canis eggs in tap water were placed
      in sealable plastic bags and subjected to 138-400 megapascals (MPa; 1 MPa=10
      atm=147 psi) for 60 s in a commercial HPP unit. We found that treatment with 300
      or 400 MPa for 60 s killed 100% of eggs using embryonation as the standard.
      Treatment with 250, 241, and 207 MPa was less effective and killed 80%, 56%, and
      8% of eggs, respectively. Results from this study suggest that HPP may be a
      useful treatment to protect foods from T. canis contamination.

PMID- 24866419
TI  - Mining and biodiversity offsets: a transparent and science-based approach to
      measure "no-net-loss".
AB  - Mining and associated infrastructure developments can present themselves as
      economic opportunities that are difficult to forego for developing and
      industrialised countries alike. Almost inevitably, however, they lead to
      biodiversity loss. This trade-off can be greatest in economically poor but highly
      biodiverse regions. Biodiversity offsets have, therefore, increasingly been
      promoted as a mechanism to help achieve both the aims of development and
      biodiversity conservation. Accordingly, this mechanism is emerging as a key tool
      for multinational mining companies to demonstrate good environmental stewardship.
      Relying on offsets to achieve "no-net-loss" of biodiversity, however, requires
      certainty in their ecological integrity where they are used to sanction habitat
      destruction. Here, we discuss real-world practices in biodiversity offsetting by
      assessing how well some leading initiatives internationally integrate critical
      aspects of biodiversity attributes, net loss accounting and project management.
      With the aim of improving, rather than merely critiquing the approach, we analyse
      different aspects of biodiversity offsetting. Further, we analyse the potential
      pitfalls of developing counterfactual scenarios of biodiversity loss or gains in
      a project's absence. In this, we draw on insights from experience with carbon
      offsetting. This informs our discussion of realistic projections of project
      effectiveness and permanence of benefits to ensure no net losses, and the risk of
      displacing, rather than avoiding biodiversity losses ("leakage"). We show that
      the most prominent existing biodiversity offset initiatives employ broad and
      somewhat arbitrary parameters to measure habitat value and do not sufficiently
      consider real-world challenges in compensating losses in an effective and lasting
      manner. We propose a more transparent and science-based approach, supported with
      a new formula, to help design biodiversity offsets to realise their potential in
      enabling more responsible mining that better balances economic development
      opportunities for mining and biodiversity conservation. 

PMID- 24866421
TI  - New population and life expectancy estimates for the Indigenous population of
      Australia's Northern Territory, 1966-2011.
AB  - BACKGROUND: The Indigenous population of Australia suffers considerable
      disadvantage across a wide range of socio-economic indicators, and is therefore
      the focus of many policy initiatives attempting to 'close the gap' between
      Indigenous and non-Indigenous Australians. Unfortunately, past population
      estimates have proved unreliable as denominators for these indicators. The aim of
      the paper is to contribute more robust estimates for the Northern Territory
      Indigenous population for the period 1966-2011, and hence estimate one of the
      most important of socio-economic indicators, life expectancy at birth. METHOD: A
      consistent time series of population estimates from 1966 to 2011, based off the
      more reliable 2011 official population estimates, was created by a mix of reverse
      and forward cohort survival. Adjustments were made to ensure sensible sex ratios
      and consistency with recent birth registrations. Standard life table methods were
      employed to estimate life expectancy. Drawing on an approach from probabilistic
      forecasting, confidence intervals surrounding population numbers and life
      expectancies were estimated. RESULTS: The Northern Territory Indigenous
      population in 1966 numbered between 23,800 and 26,100, compared to between 66,100
      and 73,200 in 2011. In 1966-71 Indigenous life expectancy at birth lay between
      49.1 and 56.9 years for males and between 49.7 and 57.9 years for females, whilst
      by 2006-11 it had increased to between 60.5 and 66.2 years for males and between
      65.4 and 70.8 for females. Over the last 40 years the gap with all-Australian
      life expectancy has not narrowed, fluctuating at about 17 years for both males
      and females. Whilst considerable progress has been made in closing the gap in
      under-five mortality, at most other ages the mortality rate differential has
      increased. CONCLUSIONS: A huge public health challenge remains. Efforts need to
      be redoubled to reduce the large gap in life expectancy between Indigenous and
      non-Indigenous Australians.

PMID- 24866422
TI  - The future of pharmacotherapy for obsessive-compulsive disorder may lie in a
      better understanding of its heterogeneity.
AB  - Pharmacological treatments currently available to treat obsessive-compulsive
      disorder (OCD) rarely produce remission. This Editorial aims to encourage more
      targeted research based on the specific OCD symptoms patients primarily present
      with. Specific OCD symptoms have been associated with distinct clinical
      characteristics, aetiological hypotheses and treatment responses. Treatment
      studies should use these findings to develop more targeted pharmacotherapy for
      patients with OCD. 

PMID- 24866423
TI  - The influence of reactive side products on the electrooxidation of methanol--a
      combined in situ infrared spectroscopy and online mass spectrometry study.
AB  - Aiming at a better understanding of the impact of reaction intermediates and
      reactive side products on electrocatalytic reactions under conditions
      characteristic for technical applications, i.e., at high reactant conversions, we
      have investigated the electrooxidation of methanol on a Pt film electrode in
      mixtures containing defined concentrations of the reaction intermediates
      formaldehyde or formic acid. Employing simultaneous in situ infrared spectroscopy
      and online mass spectrometry in parallel to voltammetric measurements, we
      examined the effects of the latter molecules on the adlayer build-up and
      composition and on the formation of volatile reaction products CO2 and
      methylformate, as well as on the overall reaction rate. To assess the individual
      contributions of each component, we used isotope labeling techniques, where one
      of the two C1 components in the mixtures of methanol with either formaldehyde or
      formic acid was (13)C-labeled. The data reveal pronounced effects of the
      additional components formaldehyde and formic acid on the reaction, although
      their concentration was much lower (10%) than that of the main reactant methanol.
      Most important, the overall Faradaic current responses and the amounts of CO2
      formed upon oxidation of the mixtures are always lower than the sums of the
      contributions from the individual components, indicative of a non-additive
      behavior of both Faradaic current and CO2 formation in the mixtures. Mechanistic
      reasons and consequences for reactions in a technical reactor, with high reactant
      conversion, are discussed. 

PMID- 24866425
TI  - Pharmacotherapy: Colchicine for recurrent pericarditis--what's new in CORP-2?

PMID- 24866426
TI  - Arrhythmias: New PACES/HRS consensus statements.

PMID- 24866428
TI  - Lower endoscopy and prevention of colon cancer.

PMID- 24866424
TI  - Contemporary overview and clinical perspectives of chronic total occlusions.
AB  - Chronic total occlusions (CTOs) are often detected on diagnostic coronary
      angiograms, but percutaneous coronary intervention (PCI) for CTO is currently
      infrequently performed owing to high technical difficulty, perceived risk of
      complications, and a lack of randomized data. However, successful CTO-PCI can
      significantly increase a patient's quality of life, improve left ventricular
      function, reduce the need for subsequent CABG surgery, and possibly improve long
      term survival. A number of factors must be taken into account for the selection
      of patients for CTO-PCI, including the extent of ischaemia surrounding the
      occlusion, the level of myocardial viability, coronary location of the CTO, and
      probability of procedural success. Moreover, in patients with ST-segment
      elevation myocardial infarction, a CTO in a noninfarct-related artery might lead
      to an increase in infarct area, increased end-diastolic left ventricular
      pressure, and decreased left ventricular function, which are all associated with
      poor clinical outcomes. In this Review, we provide an overview of the anatomy and
      histopathology of CTOs, perceived benefits of CTO-PCI, considerations for patient
      selection for this procedure, and a summary of emerging techniques for CTO-PCI. 

PMID- 24866429
TI  - Hematemesis in a patient presenting with right-sided weakness and recent
      percutaneous catheter radiofrequency ablation for atrial fibrillation.

PMID- 24866430
TI  - Bacterial translocation and nonselective beta-blockers in portal hypertension:
      where we are, what we still need.

PMID- 24866431
TI  - Massive polyposis of the sigmoid colon.

PMID- 24866432
TI  - Reply: To PMID 24047059.

PMID- 24866433
TI  - Shorter dinner-to-bed time is associated with gastric cardia adenocarcinoma risk
      partly in a reflux-dependent manner.
AB  - BACKGROUND: Gastric cancer remains the second cause of cancer-related death
      worldwide. The aim of this study was to investigate the effects of shorter dinner
      to-bed time, post-dinner walk, and obesity on gastric cardia adenocarcinoma (GCA)
      risk. METHODS: The study subjects consisted of 146 GCA patients and 166 healthy
      controls roughly matched by gender and age. Conditional logistic regression was
      used to calculated odds ratio (OR) and 95 % confidence intervals (CIs). RESULTS:
      The adjusted ORs of GCA for subjects with shorter dinner-to-bed time were 4.18
      (95 % CI 2.10-8.33) compared with those with longer dinner-to-bed time. What is
      more, when reflux symptom was added into the multivariate models, risk estimate
      for shorter dinner-to-bed time decreased greatly, but still remained
      statistically significant (p = 0.007). Post-dinner walk was associated with a
      significantly decreased GCA risk (adjusted OR 0.54; 95 % CI 0.31-0.94). When
      subjects were analyzed according to post-dinner walk, the adjusted OR of GCA for
      shorter dinner-to-bed time relative to longer dinner-to-bed time was much higher
      for non-walking subjects (adjusted OR 20.21) than walking subjects (adjusted OR
      1.39). We further found a significant interaction between shorter dinner-to-bed
      time and post-dinner walk regarding the risk of GCA (adjusted OR 0.07; p =
      0.001). CONCLUSIONS: We found that shorter dinner-to-bed time was associated with
      significantly increased GCA risk, partly depending on reflux symptoms, while post
      dinner walk was related to a significantly decreased GCA risk and could greatly
      attenuate the GCA risk attributable to shorter dinner-to-bed time.

PMID- 24866435
TI  - Evaluating the cost-effectiveness of laryngeal examination after elective total
      thyroidectomy.
AB  - BACKGROUND: Although routine laryngeal examination (RLE) after thyroidectomy may
      cost more than selective laryngeal examination (SLE), it permits earlier
      detection and treatment of vocal cord palsy (VCP) and so may be cost-saving in
      the longer term. We compared the 2-year cost-effectiveness between RLE and SLE
      with RLE performed at 2 weeks (SLE-2w), 1 month (SLE-1m), and 3 months (SLE-3m)
      after thyroidectomy in the institution's perspective. METHODS: Our case
      definition was a hypothetical 50-year-old woman who underwent an elective total
      thyroidectomy for a benign multinodular goiter. A decision-analytic model was
      constructed to compare the estimated cost-effectiveness between RLE, SLE-2w, SLE
      1m, and SLE-3m after a 2-year period. Outcome probabilities, utilities, and costs
      were estimated from the literature. The threshold for cost-effectiveness was set
      at US$50,000/quality-adjusted life-year. Sensitivity and threshold analyses were
      used to examine model uncertainty. RESULTS: RLE was not cost-effective because
      its incremental cost-effectiveness ratio to SLE-2w, SLE-1m, and SLE-3m were
      US$302,755, US$227,883 and US$247,105, respectively. RLE was only cost-effective
      when the temporary VCP rate increased >42.7 % or when the cost of RLE equaled
      zero. Similarly, SLE-2w was only cost-effective to SLE-3m when dysphonia for
      temporary VCP at 3 months increased >39.13 %, dysphonia for permanent VCP at 3
      months increased >50.29 %, or dysphonia without VCP at 3 months increased >42.69
      %. However, none of these scenarios appeared clinically likely. CONCLUSIONS: In
      the institution's perspective, RLE was not cost-effective against the other three
      SLE strategies. Regarding to the optimal timing of SLE, SLE-3m appears to be a
      reasonable and acceptable strategy because of its relative low overall cost.

PMID- 24866434
TI  - Sentinel node location in trunk and extremity melanomas: uncommon or multiple
      lymph drainage does not affect survival.
AB  - BACKGROUND: Patients with cutaneous melanoma (CM) on the trunk have a worse
      prognosis than those with extremity CM. One reason could be multiple or uncommon
      (outside axilla or groin) sentinel node locations (SNLs). METHODS: We identified
      859 patients who underwent sentinel node biopsy for trunk (n = 465) or extremity
      (n = 394) CM in three Swedish healthcare regions from 2000 to 2008. We collected
      patient, tumor, and sentinel node characteristics through clinical registers and
      medical records. We investigated the distribution of SNLs in a logistic
      regression model, and risk of overall and melanoma-specific death through 2011 in
      a multivariable Cox regression model. RESULTS: Trunk CM was associated with
      multiple SNLs (31 vs. 7 %; odds ratio [OR] 7.1; 95 % confidence interval [CI] 4.6
      11.5; p < 0.001) but not uncommon SNLs (8 vs. 7 %; OR 1.1; 95 % CI 0.6-1.9; p =
      0.75) compared with extremity CM. The increased risk of melanoma-specific death
      was confirmed for trunk CM (hazard ratio [HR] 1.9; 95 % CI 1.3-2.9; p = 0.003),
      especially on the upper back (HR 2.3; 95 % CI 1.4-3.6; p < 0.001) compared with
      extremity CM. Uncommon SNLs (HR 0.5; 95 % CI 0.2-1.4; p = 0.21) or multiple SNLs
      (HR 1.1; 95 % CI 0.4-2.9; p = 0.81) were not associated with melanoma-specific
      death compared with those with common/single SNL. CONCLUSIONS: Trunk melanomas
      were associated with multiple lymph drainage, but the worse prognosis of trunk
      melanomas could not be explained by the increased frequency of multiple or
      uncommon SNLs.

PMID- 24866437
TI  - Is resection or transplantation the ideal treatment in patients with
      hepatocellular carcinoma in cirrhosis if both are possible? A systematic review
      and metaanalysis.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common neoplasms.
      Curative treatment options include liver resection (LR) and transplantation (LT).
      Organ shortage leads to discussion whether resectable HCC in cirrhosis should
      undergo LT or LR. METHODS: Systematic review and metaanalysis of studies
      investigating LR and/or LT were performed. Overall survival (OS) and disease-free
      survival (DFS) were analyzed. Studies reporting 5-year OS of LR versus LT in an
      intention-to-treat fashion were included in a metaanalysis. RESULTS: No
      randomized controlled trial was detected. Seventy publications were eligible for
      analysis. The 5-year OS revealed a better outcome for LT than LR (60.9 vs. 49.4
      %; p < 0.001). Descriptive DFS data indicate superiority of LT at 3 years (62.0
      vs. 45.9 %; p < 0.001) and 5 years (58 vs. 33.9 %; p < 0.001). Comparing the 5
      year OS of transplantation and resection in a metaanalysis by use of the seven
      studies with a total of 1,572 patients, no survival advantage could be found
      (odds ratio, 0.84; 95 % confidence interval, 0.48-1.48; p = 0.55). CONCLUSIONS: A
      low quality of evidence data suggests the following: resectable HCC should
      primarily be resected as good alternative to liver transplantation in patients in
      whom both seem feasible. Randomized controlled trials or at least systematic
      evaluation of a cohort of patients in which resection and transplantation seem
      possible should be performed in a registry. This analysis should include
      intention-to-treat analysis of patients on the waiting list who do not proceed to
      a potential curative treatment.

PMID- 24866436
TI  - Molecular characterization and patient outcome of melanoma nodal metastases and
      an unknown primary site.
AB  - BACKGROUND: Melanoma of unknown primary site (MUP) is not a completely understood
      entity with nodal metastases as the most common first clinical manifestation. The
      aim of this multicentric study was to assess frequency and type of oncogenic
      BRAF/NRAS/KIT mutations in MUP with clinically detected nodal metastases in
      relation to clinicopathologic features and outcome. MATERIALS AND METHODS: We
      analyzed series of 103 MUP patients (period: 1992-2010) after therapeutic
      lymphadenectomy (LND): 40 axillary, 47 groin, 16 cervical, none treated with BRAF
      inhibitors. We performed molecular characterization of BRAF/NRAS/KIT mutational
      status in nodal metastases using direct sequencing of respective coding
      sequences. Median follow-up time was 53 months. RESULTS: BRAF mutations were
      detected in 55 cases (53 %) (51 V600E, 93 %; 4 others, 7 %), and mutually
      exclusive NRAS mutations were found in 14 cases (14 %) (7 p.Q61R, 4 p.Q61K, 2
      p.Q61H, 1 p.Q13R). We have not detected any mutations in KIT. The 5-year overall
      survival (OS) was 34 %; median was 24 months. We have not found significant
      correlation between mutational status (BRAF/NRAS) and OS; however, for BRAF or
      NRAS mutated melanomas we observed significantly shorter disease-free survival
      (DFS) when compared with wild-type melanoma patients (p = .04; 5-year DFS, 18 vs
      19 vs 31 %, respectively). The most important factor influencing OS was number of
      metastatic lymph nodes >1 (p = .03). CONCLUSIONS: Our large study on molecular
      characterization of MUP with nodal metastases showed that MUPs had molecular
      features similar to sporadic non-chronic-sun-damaged melanomas. BRAF/NRAS
      mutational status had negative impact on DFS in this group of patients. These
      observations might have potential implication for molecular-targeted therapy in
      MUPs.

PMID- 24866438
TI  - The emerging role of neutrophil to lymphocyte ratio in determining colorectal
      cancer treatment outcomes: a systematic review and meta-analysis.
AB  - BACKGROUND: There is growing evidence suggesting that the neutrophil to
      lymphocyte ratio (NLR) can act as an independent predictor of long-term outcomes
      in patients undergoing treatment for colorectal cancer (CRC). This study aims to
      systematically review the role of NLR in predicting survival for patients with
      CRC undergoing treatments, and to evaluate its utility within a CRC surveillance
      program. METHODS: This meta-analysis was performed according to PRISMA
      guidelines. Outcomes of interest included disease-free survival (DFS) for
      patients undergoing treatment with curative intent and progression-free survival
      (PFS) in patients undergoing treatments with palliative intent. RESULTS: Thirteen
      observational cohort studies published from 2007 to 2013 evaluated the role of
      NLR as a predictor of outcome following treatment for CRC. These included (i)
      patients undergoing surgery to resect the primary cancer (seven studies); (ii)
      those undergoing palliative chemotherapy (three studies); and (iii) patients
      undergoing potentially curative treatments for CRC liver metastases (three
      studies). When all studies were considered, a high pretreatment NLR independently
      predicted survival (HR 2.08; 95 % CI 1.64-2.64). A high NLR also predicted
      significantly poorer survival in each of the three groups. Finally, over a 3-year
      follow-up period, high NLR became a significant predictor of poor outcome at year
      2 (HR 2.76; 95 % CI 2.06-3.69; p < 0.00001) and 3 (HR 2.03; 95 % CI 1.48-2.78; p
      < 0.0001), but not in the first year of follow-up (HR 1.47; 95 % CI 0.89-2.41; p
      = 0.13). CONCLUSIONS: Elevated preoperative NLR is associated with poorer
      survival in CRC patients undergoing treatment and may have a role in CRC
      surveillance programs as a means of delivering more personalized cancer care.

PMID- 24866439
TI  - Surgeon and staff radiation exposure during radioguided parathyroidectomy at a
      high-volume institution.
AB  - INTRODUCTION: Radioguided parathyroidectomy (RGP) uses technetium-99 m sestamibi
      causing gamma ray emission during RGP to aid dissection and confirm parathyroid
      excision. Source (the patient) proximity and exposure duration determine degree
      of exposure. The purpose of this study was to quantify surgeon and staff
      radiation exposure during RGP. METHODS: Surgeons and assistants wore radiation
      dosimeters during RGP procedures at a high-volume endocrine surgery practice.
      Area dosimeters measured personnel potential exposure. Data were prospectively
      collected. Provider exposures were corrected for both duration of exposure and
      case volume. Institutional safety requirements uses 100 mrem/year as an indicator
      for radiation safety training, 500 mrem/year for personal monitoring, and a
      maximum allowed exposure of 4,500 mrem/year. RESULTS: A total of 120 RGP were
      performed over 6 months. Badges were worn in 82 cases (68 %). Three faculty and
      four assistants were included. Primary hyperparathyroidism was the diagnosis for
      95 %. Median case volume per provider was 13 cases (range 6-45), with median
      exposure of 18 h (range 9-70). Mean provider deep dose exposure (DDE) was 22 +/-
      10 mrem. Corrected for exposure duration, mean DDE was 0.6 +/- 0.2 mrem/h.
      Corrected for case volume, mean DDE was 0.8 +/- 0.2 mrem/case. Anesthesia
      exposure was minimal, while mayo stand exposure was half to two thirds that of
      the surgeon and assistant. Based on institutional guidelines and above data, 125
      RGP/year warrants safety training, 625 RGP/year warrants monitoring, whereas
      >5,600 RGP/year may result in maximum allowed radiation exposure to the surgeon.
      CONCLUSIONS: Surgeon and staff radiation exposure during RGP is minimal. However,
      high-volume centers warrant safety training.

PMID- 24866448
TI  - Synthesis of sulfonylhydrazone- and acylhydrazone-substituted 8-ethoxy-3-nitro-2H
      chromenes as potent antiproliferative and apoptosis inducing agents.
AB  - 3-Nitro-2H-chromenes have recently been identified as a novel class of potent
      antitumor agents. In view of the favorable effects shown by sulfonylhydrazones
      and acylhydrazones, we designed and synthesized a series of sulfonylhydrazone-
      and acylhydrazone-substituted 8-ethoxy-3-nitro-2H-chromene derivatives, and
      evaluated their cell growth inhibition activities against A549, KG-1, A2780, and
      K562 cells. All the tested compounds exhibited more potent antiproliferative
      activity than BENC-511 against KG-1 cells. These compounds displayed IC50 values
      in the nanomolar range against A2780 cells. Compound 7d showed prominent
      cytotoxicity against K562 cells with an IC50 of 0.11 uM, which was comparable to
      that of BENC-511. Compound 7d arrested K562 cells at the G1 phase at high
      concentrations and induced apoptosis in K562 cells. Furthermore, 7d increased the
      levels of cleaved caspase-3, decreased the expression of bcl-2 and induced the
      cleavage of poly(ADP-ribose) polymerase in K562 cells. Thus, this study provides
      the development of a series of novel compounds as effective antitumor agents with
      apoptotic death ability. 

PMID- 24866453
TI  - Attention orienting by eye gaze and arrows reveals flexibility to environmental
      changes.
AB  - This study aimed to evaluate the difference in non-predictive cues between gaze
      and arrows in attention orienting. Attention orienting was investigated with gaze
      or arrows as separate cues in a simple condition (i.e., block design) in
      Experiment 1 and in an unpredictable condition (i.e., randomized design) in
      Experiment 2. Two kinds of sound (voice and tone) stimuli were used as targets.
      Results showed that gaze and arrow cues induced enhanced attention orienting to a
      voice versus tone target in the block condition. However, in the randomized
      condition, enhanced attention orienting to a voice versus tone target was found
      in gaze but not arrow cues. The congruency of the meaning between a social cue
      (i.e., gaze) and a social target (i.e., voice) was clear in the randomized but
      not blocked design, because social gaze and non-social arrow cues were
      implemented in the same block. Thus, attention orienting might be mediated by the
      associated relationship of cue-target in a randomized condition, as an enhanced
      orienting effect was found when the associated relationship of cue-target was
      strong (i.e., social cue and target). The present study suggests that the
      difference in attention orienting between gaze and arrows is apparent in a
      randomized design (the unpredictable condition), and people employ a flexibly
      strategy of orienting to better respond to environmental changes. 

PMID- 24866454
TI  - Can dancers suppress the haptically mediated interpersonal entrainment during
      rhythmic sway?
AB  - Interpersonal entrainment emerges spontaneously when partners performing rhythmic
      movements together exchange sensory feedback about the other's movements. In this
      study, we asked whether couples of expert dancers, non-dancers and mixed couples
      can suppress the spontaneous haptically mediated inter-personal entrainment when
      their rhythmic sway is paced by differing metronome tempos. Fifty-four young
      participants formed three types of couples: nine dancer couples, consisting of
      individuals with at least eight years systematic practice in traditional Greek
      dance; nine non-dancer couples, consisting of individuals with no prior
      experience in dance and nine mixed couples, consisting of one dancer and one
      novice partner. Partners swayed rhythmically for 60 s, at different pacing
      frequencies (one at 0.25 Hz and the other at 0.35 Hz) under three haptic contact
      conditions: no contact between them; light fingertip touch established in the 2nd
      trial segment (30 s); and light fingertip touch released in the 2nd trial segment
      (30 s). Spectral analysis of the antero-posterior center of pressure displacement
      revealed that light touch increased the deviation of the dominant from the target
      (pacing) sway frequency, decreased the proportion of the signal's power at the
      target frequency and increased the coherence between the partners' sway signals
      (inter-personal coherence). These effects were specific to the mixed group
      whereas touch interference was weaker in non-dancers and absent in dancers. In
      addition, the coherence between the trial segments (intra-personal coherence)
      significantly decreased with touch only for the non-dancer while it remained
      unchanged for the dancer partner of the mixed group suggesting that the dancer
      was leading the non-dancer partner. It is concluded that systematic practice with
      traditional dance can modulate the spontaneous tendency towards haptically
      mediated interpersonal entrainment.

PMID- 24866449
TI  - Combination of beta-carotene and quercetin against benzo[a]pyrene-induced pro
      inflammatory reaction accompanied by the regulation of antioxidant enzyme
      activity and NF-kappaB translocation in Mongolian gerbils.
AB  - PURPOSE: We have previously shown that quercetin modulates the proinflammatory
      effect of beta-carotene (BC) induced by oral benzo[a]pyren (Bap) partly through
      the regulation of the JNK pathway. In the present study, we determined whether
      the combination of BC and quercetin regulates the antioxidant enzymes and the
      activation of NF-kappaB in Mongolian gerbils exposed to Bap. We also compared the
      combined effects of BC+ quercetin with that of BC+ ascorbic acid (C)+ alpha
      tocopherol (E). METHODS: The gerbils were given BC (10 mg/kg) alone or in
      combination with quercetin (50 or 100 mg/kg) or C (13 mg/kg)+E (92 mg/kg) by
      gavage 3 times/week for 6 months. During the first 2 months, the gerbils were
      exposed to Bap by intratracheal instillation once/week. The levels of
      proinflammatory cytokines, thiobarbituric acid reactive substances, antioxidant
      enzymes and NF-kappaB activation in the plasma or the lungs were determined.
      RESULTS: Bap increased the level of proinflammatory cytokines and oxidative
      stress in the plasma or lungs, while it decreased the antioxidant systems. Bap
      also increased nuclear NF-kappaB levels in the lungs. BC partly recovered the Bap
      induced decrease in antioxidant activity, antioxidant enzyme activities and
      glutathione levels but had no effect on proinflammatory cytokines and NF-kappaB
      translocation. BC in combination with quercetin or C+E suppressed all the harmful
      effects induced by Bap. All the effects of quercetin at 100 mg/kg were similar to
      the effect of C+E. CONCLUSION: BC in combination with quercetin or C+E rather
      than BC alone similarly suppresses the Bap-induced inflammatory reaction that was
      accompanied by the regulation of antioxidant enzymes and the translocation of NF
      kappaB in vivo.

PMID- 24866455
TI  - Imagination perspective affects ratings of the likelihood of occurrence of
      autobiographical memories.
AB  - Two experiments tested and confirmed the hypothesis that when the
      phenomenological characteristics of imagined events are more similar to those of
      related autobiographical memories, the imagined event is more likely to be
      considered to have occurred. At Time 1 and 2-weeks later, individuals rated the
      likelihood of occurrence for 20 life events. In Experiment 1, 1-week after Time
      1, individuals imagined 3 childhood events from a first-person or third-person
      perspective. There was a no-imagination control. An increase in likelihood
      ratings from Time 1 to Time 2 resulted when imagination was from the third-person
      but not first-person perspective. In Experiment 2, childhood and recent events
      were imagined from a third- or first-person perspective. A significant
      interaction resulted. For childhood events, likelihood change scores were greater
      for third-person than first-person perspective; for recent adult events,
      likelihood change scores were greater for first-person than third-person
      perspective, although this latter trend was not significant. 

PMID- 24866457
TI  - Expression of muscarinic acetylcholine receptors M3 and M5 in osteoporosis.
AB  - BACKGROUND: Cholinergic signaling via muscarinic acetylcholine receptors (mAChR)
      is known to influence various physiological functions. In bone, M3 mAChR and M5
      mAChR were identified on the membrane of osteoblast-like cells. M3 mAChR seems to
      be particularly relevant for bone physiology, as signaling via this receptor was
      reported to increase bone formation and decrease bone resorption. Thus, in the
      present study we investigated the relative mRNA expression of M3 and M5 mAChR in
      bones of a rat osteoporosis model. MATERIAL AND METHODS: Osteoporosis was induced
      in Sprague-Dawley rats by bilateral ovariectomy and additional feeding of a diet
      deficient in calcium, vitamins C, D2, D3, and phosphorus, and free of soy and
      phytoestrogen. After a period of 3, 12, and 14 months, relative mRNA expression
      of M3 mAChR and M5 mAChR was analyzed in the 11th thoracic vertebra by real-time
      RT-PCR. RESULTS: Relative mRNA expression of M3 mAChR was significantly reduced
      in bones of osteoporotic rats compared to sham operated animals that served as
      controls. Further, M3 mAChR mRNA expression was significantly down-regulated when
      comparing 14-month osteoporotic rats to 3-month osteoporotic rats. Relative M5
      mAChR mRNA was expressed to a lesser extent than M3 mAChR and did not show
      significant differences in mRNA expression level between the experimental groups.
      CONCLUSIONS: M3 mAChR mRNA expression was reduced upon induction of osteoporosis
      and progression of disease was associated with further decrease of this receptor,
      indicating that M3 mAChR is involved in the development and regulation of
      osteoporosis.

PMID- 24866458
TI  - Neuropsychiatric symptoms in Parkinson's disease: fronto-striatal atrophy
      contributions.
AB  - BACKGROUND: Neuropsychiatric symptoms (NPS) in Parkinson's disease (PD) have been
      mostly attributed to neurotransmitter imbalances. However, recent findings
      suggest that gray matter atrophy also contributes to NPS in PD. We contrast PD
      patients with different levels of NPS, who are well-matched for dopaminergic
      medication levels and disease stage, to identify the fronto-striatal gray matter
      atrophy areas associated with NPS in PD. METHODS: Fifty mild, non-demented PD
      patients were included. We median-split the group via a neuropsychiatric
      screening tool (Cambridge Behavioural Inventory-Revised), which resulted in
      higher vs. lower NPS groups (n = 25 in each group). Using T1 brain scans acquired
      on a 3 Tesla MRI scanner, voxel-based morphometry analysis was applied to
      characterize the pattern of fronto-striatal gray matter atrophy associated with
      elevated NPS. RESULTS: We found that the higher NPS group was characterized by
      greater atrophy in the prefrontal cortex, but not striatal areas. This was
      further corroborated by a post-hoc analysis cross-correlating the severity of NPS
      with gray matter loss across the whole PD group, which revealed that atrophy in
      the orbitofrontal cortex and frontal pole was specifically associated with
      elevated NPS. CONCLUSIONS: Prefrontal cortex atrophy in PD has an additional
      effect to dopamine replacement therapy on the generation of NPS in these
      patients. These findings are an important step towards the delineation of atrophy
      vs. neurochemical imbalance in PD, and the results emphasize the importance of
      considering interactions between prefrontal atrophy and neurochemical dysfunction
      in the genesis of neuropsychiatric symptoms in PD.

PMID- 24866460
TI  - Rapid diagnosis of mediastinal tuberculosis with polymerase chain reaction
      evaluation of aspirated material taken by endobronchial ultrasound-guided
      transbronchial needle aspiration.
AB  - BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration
      (EBUS-TBNA) is a diagnostic method for tuberculosis (TB). This study was
      conducted to determine the efficiency of polymerase chain reaction (PCR) testing
      for detecting TB lymphadenitis in samples obtained by EBUS-TBNA. MATERIALS AND
      METHODS: A total of 93 consecutive patients with hilar/mediastinal
      lymphadenopathies and diagnosed with granulomatous diseases through
      histopathological evaluation were included in the study. The specimens provided
      by EBUS-TBNA were evaluated through pathological, microbiological, and molecular
      tests. RESULTS: Eighty-nine (95.7%) of the 93 patients had histopathologically
      granulomatous diseases by EBUS-TBNA. Tuberculosis was diagnosed in 27 (30.3%)
      patients and sarcoidosis was diagnosed in 62 (69.7%) patients. Four (4.3%)
      patients were diagnosed through mediastinoscopy. Endobronchial ultrasound-guided
      transbronchial needle aspiration had an overall diagnostic efficiency in TB of
      96.9%, a sensitivity of 90.9%, and a specificity of 100%. Mycobacterium
      tuberculosis PCR was positive in 17 of the 30 patients. The sensitivity of PCR
      was 56.7%, the specificity was 100%, and the general efficiency of the test was
      96.4%. CONCLUSIONS: As a result, the use of M. tuberculosis PCR in the EBUS-TBNA
      specimens provides a rapid and an accurate diagnosis of TB. Therefore, we
      recommend the use of M. tuberculosis PCR in the EBUS-TBNA specimens as a rapid
      diagnostic method for mediastinal lymphadenopathies in patients with suspected
      TB.

PMID- 24866459
TI  - Short-term effects of corticosteroid therapy on cardiac and skeletal muscles in
      muscular dystrophies.
AB  - BACKGROUND: Duchenne muscular dystrophy (DMD) is the most common muscular
      dystrophy of childhood. It leads to progressive deterioration in cardiac and
      skeletal muscles. Corticosteroids are considered an effective therapy. OBJECTIVE:
      This study aimed to evaluate the role of short-term prednisone therapy in
      improving left ventricular (LV) systolic function, LV mass (LVM), and motor power
      in cases of muscular dystrophies. PATIENTS AND METHODS: Twenty-five cases of
      muscular dystrophy including 17 cases of DMD, 3 cases of Becker muscular
      dystrophies, and 5 cases of female patients with DMD-like phenotype were included
      in the study. The diagnosis of 12 patients was confirmed by muscle biopsy with
      immunohistochemistry; the patients were subjected to motor assessment,
      measurement of creatine kinase level, and echocardiographic examination before
      and after prednisone therapy. Transthoracic echocardiographic assessment of the
      LV systolic function (fractional shortening) was done. Myocardial performance
      index and LVM were calculated. Intermittent dosage of prednisone was administered
      5 mg/kg per day on 2 consecutive days weekly for 3 months. RESULTS: Fractional
      shortening improved on prednisone therapy (P = 0.009) and LVM increased (P =
      0.012); improvement in walking was detected in 77% of the patients, climbing
      stairs improved in 88.9%, Gower sign improved in 70%, and rising from chair
      improved in 60%. Prednisone had no effect on the patients with marked motor
      impairment (on wheelchair). The creatine kinase level was significantly lower
      after steroid therapy (P = 0.04). CONCLUSIONS: Three months of intermittent
      prednisone therapy could improve cardiac and skeletal muscle function in
      congenital muscular dystrophy.

PMID- 24866462
TI  - Antenatal taurine improves neuronal regeneration in fetal rats with intrauterine
      growth restriction by inhibiting the Rho-ROCK signal pathway.
AB  - The Rho-ROCK signal pathway is an important mediator of inhibitory signals that
      blocks central nervous cell regeneration. Here, we investigated whether antenatal
      taurine improved neuronal regeneration in fetal rats with intrauterine growth
      restriction (IUGR) by inhibiting this pathway. Thirty pregnant rats were randomly
      divided into three groups: control, IUGR, and IUGR + antenatal taurine
      supplementation (taurine group). The mRNA levels of Ras homolog gene A (Rho A),
      Rho-associated coiled-coil forming protein kinase 2 (ROCK2), and proliferating
      cell nuclear antigen (PCNA) were detected using real-time quantitative PCR. RhoA,
      ROCK2 and PCNA-positive cells were counted using immunohistochemistry. Antenatal
      taurine supplementation decreased RhoA and Rock2 mRNA expression, increased PCNA
      mRNA expression, and significantly decreased RhoA, ROCK2-positive and increased
      PCNA-positive cell counts in IUGR fetal rat brain tissues (p < 0.05). Thus,
      antenatal taurine supplementation inhibited the expression of key Rho-ROCK signal
      molecules and improved IUGR fetal brain development.

PMID- 24866463
TI  - Review of studies that have used knockout mice to assess normal function of prion
      protein under immunological or pathophysiological stress.
AB  - Deletion of cellular isoform of prion protein (PrP(C)) increases neuronal
      predisposition to damage by modulating apoptosis and the negative consequences of
      oxidative stress. In vivo studies have demonstrated that PrP(C)-deficient mice
      are more prone to seizure, depression, and induction of epilepsy and experience
      extensive cerebral damage following ischemic challenge or viral infection. In
      addition, adenovirus-mediated overexpression of PrP(C) reduces brain damage in
      rat models of cerebral ischemia. In experimental autoimmune encephalomyelitis,
      PrP(C)-deficient mice reportedly have a more aggressive disease onset and less
      clinical improvement during the chronic phase than wild-type mice mice. In mice
      given oral dextran sulfate, PrP(C) has a potential protective role against
      inflammatory bowel disease. PrP(C)-deficient mice demonstrate significantly
      greater increases in blood glucose concentrations after intraperitoneal injection
      of glucose than wild-type mice. Further in vivo challenges to PrP gene-deficient
      models and conditional knockout models with siRNA and in vivo administration of
      PrP-ligating agents may assist in refining knowledge of the lymphoid function of
      PrP(C) and predicting the effects of anti-PrP treatment on the immune system.
      Together, these findings indicate that PrP(C) may have multiple neuroprotective
      and anti-inflammatory roles, which explains why this protein is so widely
      expressed.

PMID- 24866464
TI  - Mitochondrial protein translocases for survival and wellbeing.
AB  - Mitochondria are involved in many essential cellular activities. These broad
      functions explicate the need for the well-orchestrated biogenesis of
      mitochondrial proteins to avoid death and pathological consequences, both in
      unicellular and more complex organisms. Yeast as a model organism has been
      pivotal in identifying components and mechanisms that drive the transport and
      sorting of nuclear-encoded mitochondrial proteins. The machinery components that
      are involved in the import of mitochondrial proteins are generally evolutionarily
      conserved within the eukaryotic kingdom. However, topological and functional
      differences have been observed. We review the similarities and differences in
      mitochondrial translocases from yeast to human. Additionally, we provide a
      systematic overview of the contribution of mitochondrial import machineries to
      human pathologies, including cancer, mitochondrial diseases, and
      neurodegeneration. 

PMID- 24866469
TI  - The declining demand for hospital care as a rationale for duty hour reform.
AB  - The regulation of duty hours of physicians in training remains among the most
      hotly debated subjects in medical education. Although recent duty hour reforms
      have been chiefly motivated by concerns about resident well-being and medical
      errors attributable to resident fatigue, the debate surrounding duty hour reform
      has infrequently involved discussion of one of the most important secular changes
      in hospital care that has affected nearly all developed countries over the last 3
      decades: the declining demand for hospital care. For example, in 1980, we show
      that resident physicians in US teaching hospitals provided, on average, 1,302
      inpatient days of care per resident physician compared to 593 inpatient days in
      2011, a decline of 54%. This decline in the demand for hospital care by residents
      provides an under-recognized economic rationale for reducing residency duty
      hours, a rationale based solely on supply and demand considerations. Work hour
      reductions and growing requirements for outpatient training can be seen as an
      appropriate response to the shrinking demand for hospital care across the health
      care sector.

PMID- 24866470
TI  - Resonant multiple light scattering for enhanced photon harvesting in dye
      sensitized solar cells.
AB  - A new benchmark for DSSC performances is set using a novel dye and fabricating a
      very efficient resonant light-scattering device with a high photocurrent and good
      stability. 

PMID- 24866468
TI  - Temporal trends in treatment outcomes for HIV-1 and HIV-2-infected adults
      enrolled in Cote d'Ivoire's national antiretroviral therapy program.
AB  - BACKGROUND: In Cote d'Ivoire during 2004-2007, numbers of ART enrollees increased
      from <5,000 to 36,943. Trends in nationally representative ART program outcomes
      have not yet been reported. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a
      retrospective chart review to assess trends in patient characteristics and
      attrition [death or loss to follow-up (LTFU)] over time, among a nationally
      representative sample of 3,682 adults (>=15 years) initiating ART during 2004
      2007 at 34 health facilities. Among ART enrollees during 2004-2007, median age
      was 36, the proportion female was 67%, the proportion HIV-2-infected or dually
      HIV-1&2 reactive was 5%, and median baseline CD4+ T-cell (CD4) count was 135
      cells/uL. Comparing cohorts initiating ART in 2004 with cohorts initiating ART in
      2007, median baseline weight declined from 55 kg to 52 kg (p = 0.008) and the
      proportion weighing <45 kg increased from 17% to 22% (p = 0.014). During 2004
      2007, pharmacy-based estimates of the percentage of new ART enrollees >=95%
      adherent to ART declined from 74% to 60% (p = 0.026), and twelve-month retention
      declined from 86% to 69%, due to increases in 12-month mortality from 2%-4% and
      LTFU from 12%-28%. In univariate analysis, year of ART initiation was associated
      with increasing rates of both LTFU and mortality. Controlling for baseline CD4,
      weight, adherence, and other risk factors, year of ART initiation was still
      strongly associated with LTFU but not mortality. In multivariate analysis, weight
      <45 kg and adherence <95% remained strong predictors of LTFU and mortality.
      CONCLUSIONS: During 2004-2007, increasing prevalence among ART enrollees of
      measured mortality risk factors, including weight <45 kg and ART adherence <95%,
      might explain increases in mortality over time. However, the association between
      later calendar year and increasing LTFU is not explained by risk factors
      evaluated in this analysis. Undocumented transfers, political instability, and
      patient dissatisfaction with crowded facilities might explain increasing LTFU.

PMID- 24866471
TI  - The epidemiology and spread of drug resistant human influenza viruses.
AB  - Significant changes in the circulation of antiviral-resistant influenza viruses
      have occurred over the last decade. The emergence and continued circulation of
      adamantane-resistant A(H3N2) and A(H1N1)pdm09 viruses mean that the adamantanes
      are no longer recommended for use. Resistance to the newer class of drugs, the
      neuraminidase inhibitors, is typically associated with poorer viral replication
      and transmission. But 'permissive' mutations, that compensated for impairment of
      viral function in A(H1N1) viruses during 2007/2008, enabled them to acquire the
      H275Y NA resistance mutation without fitness loss, resulting in their rapid
      global spread. Permissive mutations now appear to be present in A(H1N1)pdm09
      viruses thereby increasing the risk that oseltamivir-resistant A(H1N1)pdm09
      viruses may also spread globally, a concerning scenario given that oseltamivir is
      the most widely used influenza antiviral. 

PMID- 24866472
TI  - Literature research of the Nutrition Improvement Programme for Rural Compulsory
      Education Students in China.
AB  - OBJECTIVE: To describe the Nutrition Improvement Programme for Rural Compulsory
      Education Students (NIPRCES) in China and to share the experiences of developing
      and implementing nationwide school meal programmes with other countries. DESIGN:
      The article is based on a literature review of technical documents and reports of
      NIPRCES and relevant national legislation, technical reports and studies on
      school nutrition, minutes of meetings and national conferences, and official
      documents of the National Office of Student Nutrition and the Chinese Center for
      Disease Control and Prevention. SETTING: People's Republic of China. SUBJECTS:
      Published papers, national policies, legislation and unpublished official
      documents. RESULTS: A total of 23 million rural compulsory education students
      were covered by NIPRCES. In the development and implementation process of
      NIPRCES, fifteen ministries and national committees were involved and an
      efficient collaborative mechanism was established. All NIPRCES-covered schools
      were required to serve meals on a daily basis. By the end of June 2012, the
      proportions of students choosing 'school feeding', 'food package' and 'family
      feeding' modes were respectively 64.0 %, 32.0 % and 4.0 %. The central government
      subsidized school meals annually by more than $US 2.5 billion and invested $US
      4.8 billion on school kitchens to support this programme. CONCLUSIONS: The
      NIPRCES is a significant movement of governmental nutritional intervention in
      China. Food safety, financial security, decentralization and other potential
      concerns should be considered and lessons can be learned from other countries.
      Further relevant research and a nationwide monitoring and evaluation programme
      are needed.

PMID- 24866473
TI  - Long-term outcomes in adult patients with ischemic-type moyamoya disease
      involving posterior circulation.
AB  - BACKGROUND: The object of this study was to compare the long-term outcomes in
      adult patients with moyamoya disease (MMD) with posterior circulation involvement
      (PCi) treated through surgical revascularization with those in adult patients
      without PCi. METHODS: The records of 32 consecutive adult patients with ischemic
      type MMD who were treated with revascularization were reviewed. Twelve of these
      patients (38 %) had PCi at initial onset. Clinical characteristics of the
      patients with PCi were compared to those without PCi. Neurological outcomes were
      assessed using the modified Rankin Scale (mRS) in the preoperative and
      postoperative follow-up periods. A five-year Kaplan-Meier stroke risk was
      calculated. RESULTS: The frequency of presenting with infarction was
      significantly higher among patients with PCi than among those without PCi (p =
      0.006). mRS scores in the preoperative period were significantly higher in
      patients with PCi than in patients without PCi (p = 0.0004). There were no
      significant differences in mRS scores between the preoperative and postoperative
      follow-up period in patients with PCi (p = 0.3), nor were there any between the
      preoperative and postoperative follow-up periods in patients without PCi (p =
      0.2). The five-year Kaplan-Meier risk of surgical morbidity and ipsilateral
      stroke was 14.3 % in surgically treated hemispheres with PCi versus 14.9 % in
      surgically treated hemispheres without PCi (p = 0.96). CONCLUSIONS: PCi at
      initial onset was significantly correlated with poor outcome. Revascularization
      for the middle cerebral artery territory in patients with PCi was effective at
      preventing recurrent ischemic stroke.

PMID- 24866474
TI  - Clinical outcome of adult choroid plexus tumors: retrospective analysis of a
      single institute.
AB  - BACKGROUND: Choroid plexus tumors are rare brain tumors with clinical features
      that vary according to the histological grade. We reviewed the treatment outcomes
      of 15 adult patients with choroid plexus tumors, focusing on surgical outcomes
      and current therapeutic strategies. METHOD: Patient demographic and clinical
      characteristics, operative findings, adjuvant therapies, disease progression and
      survival rates were reviewed. RESULTS: The median age at diagnosis was 33.7 +/-
      10 years (19-59 years) for patients with choroid plexus tumors. Postoperative
      chemotherapy was given to 26.7 % of patients, and 13.3 % of patients received
      radiotherapy. The Ki-67 labeling index and mitotic index increased at higher
      histological grades. All of the choroid plexus papilloma and atypical choroid
      plexus papilloma patients have survived. The overall survival rate of patients
      with choroid plexus carcinoma was 50 % in the first year, but none of the
      patients survived to the second year. Five patients underwent permanent
      cerebrospinal fluid diversion surgery because of hydrocephalus or subdural
      effusion. CONCLUSIONS: Choroid plexus papilloma and atypical choroid plexus
      papilloma patients can be treated with complete surgical resection. Choroid
      plexus carcinoma has a poor prognosis, and aggressive multi-modal treatments are
      generally needed for treatment. Chemotherapy and radiotherapy are important
      adjuvant therapies for choroid plexus carcinoma. If hydrocephalus and/or subdural
      effusion occur, permanent cerebrospinal fluid (CSF) diversion should be added to
      the therapeutic strategy.

PMID- 24866475
TI  - The role of open access in reducing waste in medical research.

PMID- 24866476
TI  - The ophthalmology microscalpel versus standard scalpels and wound healing in a
      rat model.
AB  - OBJECTIVE: We tested the hypothesis that the ophthalmology microscalpel, compared
      to standard incisional instruments, causes less trauma during incisions resulting
      in decreased inflammation and greater tensile strength of wounds. STUDY DESIGN:
      Prospective animal study. SETTING: Animal laboratory. SUBJECTS AND METHODS:
      Thirty-four Sprague-Dawley rats received dorsum skin incisions with the
      microscalpel, electrosurgical device, 11 blade scalpel, and 15 blade scalpel.
      Wounds were harvested at 1 week, 2 weeks, 3 weeks, and 6 weeks, then analyzed
      histologically in a blinded manner for inflammation markers and tested for
      tensile strength. RESULTS: The microscalpel wounds had significantly higher
      tensile strength compared to the 15 blade (P = .045) and electrocautery device (P
      = .000) but equivocal strength to the 11 blade (P = .457). The electrocautery
      wounds were weaker than all 3 steel blades. No significant difference was found
      between the microscalpel, 11 blade, and 15 blade incisions for the 5 markers of
      inflammation. Electrocautery wounds had significantly worse inflammatory scores,
      specifically, higher angiogenesis and larger wound gap compared to the
      microscalpel (P = .004, P = .002), 11 blade (P = .007, P = .023), and 15 blade (P
      = .010, P = .003), respectively. CONCLUSION: Microscalpel incisions result in
      less inflammation and increased tensile strength compared with electrocautery and
      higher tensile strength compared to the 15 blade in the rat model. Inflammation
      scores were equivocal between the microscalpel, 11 blade, and 15 blade. Our
      findings support the use of the microscalpel blade for facial plastic and
      reconstructive procedures. Prospective, randomized human studies are warranted.

PMID- 24866477
TI  - Biofunctional surface patterns retaining activity after exposure to whole blood.
AB  - Biofunctional surface patterns capable of resisting nonspecific bioadsorption
      while retaining bioactivity play crucial roles in the advancement of life science
      and biomedical technologies. The currently available functional surface coatings
      suffer from a high level of nonspecific surface adsorption of proteins under
      biologically challenging conditions, leading to a loss of activity in functional
      moieties over time. In this study, the recently discovered facile method of
      temperature-induced polyelectrolyte (TIP) grafting has been used to graft two
      biofunctional variants (biotin and nitrilotriacetic acid, NTA) of poly(l-lysine)
      grafted PEG (PLL-g-PEG) onto a titanium surface. A significant increase in the
      polymer adsorption was observed from the TIP-grafted surfaces assembled at 80 
      degrees C, compared to the polymer surfaces assembled at ambient temperature (20 
      degrees C). These functional PLL-g-PEG surfaces were subsequently incubated in
      whole human blood continuously for up to 7 days, and the TIP-grafted surfaces
      achieved close-to-zero nonspecific protein adsorption, as confirmed by
      ultrasensitive time-of-flight secondary ion mass spectrometry (ToF-SIMS). To test
      the maintenance of the bioactivity of the biotin and NTA moieties, submicrometer
      scale mono- (biotin) and bi- (biotin/NTA) functional surface chemical patterns
      were fabricated via two-step TIP grafting using colloidal lithography (CL),
      preincubated in blood for up to 7 days and sequentially exposed to streptavidin
      and Ni(2+)-histidine-tagged calmodulin. The fluorescence microscopy studies
      revealed that the PLL-g-PEG-NTA and -biotin surfaces grafted from the TIP method
      were still capable of recognizing the corresponding affinity proteins for up to 1
      and 7 days of preincubation in blood, respectively. These results highlight the
      bioresistant robustness realized by the facile TIP grafting method, which in turn
      preserves the activities of biofunctional moieties over a prolonged period in
      whole blood. 

PMID- 24866478
TI  - Heightened response of eosinophilic asthmatic patients to the CRTH2 antagonist
      OC000459.
AB  - BACKGROUND: The CRTH2 antagonist OC000459 has previously been demonstrated to
      reduce airway inflammation and improve lung function in moderate persistent
      asthma. A study was conducted to determine the effect of lower once daily doses
      of OC000459 and to define the phenotype of subjects most responsive to treatment.
      METHODS: Adult subjects (percentage of predicted forced expiratory volume in 1 s
      (FEV1 ) 60-85%) were randomized to OC000459 at three dose levels (25 mg once
      daily, 200 mg once daily or 100 mg twice daily) or placebo for 12 weeks (n = 117
      125 per group, full analysis set). The primary endpoint was the change from
      baseline in prebronchodilator FEV1 , and secondary endpoints included Asthma
      Control Questionnaire (ACQ) and Standardised Asthma Quality of Life Questionnaire
      [AQLQ(S)], and incidence of exacerbations and respiratory tract infections.
      RESULTS: OC459 caused a significant improvement in FEV1 compared with placebo at
      a dose of 25 mg once daily (P = 0.028). A similar increase was observed in the
      other dose groups, and the mean change in FEV1 in the pooled dose groups at
      endpoint was 95 ml greater than placebo (P = 0.024). In a post hoc analysis of
      atopic eosinophilic subjects with uncontrolled asthma, a mean increase in FEV1 of
      220 ml was observed compared with placebo (P = 0.005). The mean increase in FEV1
      was more marked in younger subjects in this group: for subjects aged <=40 years,
      there was a mean increase of 355 ml compared with placebo (P = 0.007).
      Improvements in ACQ and AQLQ(S) were observed in both the full analysis set and
      the atopic eosinophilic subgroup. There was a lower incidence of exacerbations
      and respiratory infections in subjects treated with OC000459. There were no drug
      related serious adverse events. CONCLUSIONS: OC000459 is a safe and effective
      oral anti-inflammatory agent, which achieved clinically meaningful improvements
      in lung function and asthma control in allergic asthmatics with an eosinophil
      dominant form of the disease. A dose of 25 mg given once daily was as effective
      as the higher doses studied.

PMID- 24866480
TI  - An Algorithm for Generating Small RNAs Capable of Epigenetically Modulating
      Transcriptional Gene Silencing and Activation in Human Cells.

PMID- 24866479
TI  - Interaction between ions and substituted buckybowls: a comprehensive
      computational study.
AB  - Complexes formed by substituted buckybowls derived from corannulene and sumanene
      with sodium cation or chloride anion have been computationally studied by using a
      variety of methods. Best results have been obtained with the SCS-MP2 method
      extrapolated to basis set limit, which reproduces the highest-level values
      obtained with the MP2.X method. All bowls form stable complexes with chloride
      anion, with stabilities ranging from -6 kcal/mol in the methylated corannulene
      derivative to -45 kcal/mol in the CN-substituted sumanene. The opposite trend is
      observed in sodium complexes, going from deeply attractive complexes with the
      methylated derivatives (-36 kcal/mol with sumanene derivative) to slightly
      repulsive ones in the CN-substituted bowls (2 kcal/mol in the corannulene
      derivative). Anion complexes are stabilized by large electrostatic interactions
      combined with smaller though significant dispersion and induction contributions.
      Conversely, cation complexes are stabilized by large induction contributions
      capable of holding together the bowl and the cation even in cases where the
      electrostatic interaction is repulsive. The effect of substitution is mainly
      reflected on changes in the molecular electrostatic potential of the bowl and,
      thus, in the electrostatic contribution to the interaction. Therefore, the
      variations in the stability of the complexes on substitution could be roughly
      predicted just considering the changes in the electrostatic interaction. However,
      other contributions also register changes mainly as a consequence of
      displacements on the position of the ion at the minimum, so the accurate
      prediction of the stability of this kind of complexes requires going further than
      the electrostatic approach.

PMID- 24866481
TI  - Production of CMAH Knockout Preimplantation Embryos Derived From Immortalized
      Porcine Cells Via TALE Nucleases.
AB  - Although noncancerous immortalized cell lines have been developed by introducing
      genes into human and murine somatic cells, such cell lines have not been
      available in large domesticated animals like pigs. For immortalizing porcine
      cells, primary porcine fetal fibroblasts were isolated and cultured using the
      human telomerase reverse transcriptase (hTERT) gene. After selecting cells with
      neomycin for 2 weeks, outgrowing colonized cells were picked up and subcultured
      for expansion. Immortalized cells were cultured for more than 9 months without
      changing their doubling time (~24 hours) or their diameter (< 20 um) while
      control cells became replicatively senescent during the same period. Even a
      single cell expanded to confluence in 100 mm dishes. Furthermore, to knockout the
      CMAH gene, designed plasmids encoding a transcription activator-like effector
      nuclease (TALENs) pairs were transfected into the immortalized cells. Each single
      colony was analyzed by the mutation-sensitive T7 endonuclease I assay,
      fluorescent PCR, and dideoxy sequencing to obtain three independent clonal
      populations of cells that contained biallelic modifications. One CMAH knockout
      clone was chosen and used for somatic cell nuclear transfer. Cloned embryos
      developed to the blastocyst stage. In conclusion, we demonstrated that
      immortalized porcine fibroblasts were successfully established using the human
      hTERT gene, and the TALENs enabled biallelic gene disruptions in these
      immortalized cells. 

PMID- 24866482
TI  - Attenuation coefficients for water quality trading.
AB  - Water quality trading has been proposed as a cost-effective approach for reducing
      nutrient loads through credit generation from agricultural or point source
      reductions sold to buyers facing costly options. We present a systematic approach
      to determine attenuation coefficients and their uncertainty. Using a process
      based model, we determine attenuation with safety margins at many watersheds for
      total nitrogen (TN) and total phosphorus (TP) loads as they transport from point
      of load reduction to the credit buyer. TN and TP in-stream attenuation generally
      increases with decreasing mean river flow; smaller rivers in the modeled region
      of the Ohio River Basin had TN attenuation factors per km, including safety
      margins, of 0.19-1.6%, medium rivers of 0.14-1.2%, large rivers of 0.13-1.1%, and
      very large rivers of 0.04-0.42%. Attenuation in ditches transporting nutrients
      from farms to receiving rivers is 0.4%/km for TN, while for TP attenuation in
      ditches can be up to 2%/km. A 95 percentile safety margin of 30-40% for TN and 6
      10% for TP, applied to the attenuation per km factors, was determined from the in
      stream sensitivity of load reductions to watershed model parameters. For
      perspective, over 50 km a 1% per km factor would result in 50% attenuation = 2:1
      trading ratio. 

PMID- 24866483
TI  - Palladium-catalyzed cascade annulation to construct functionalized beta- and
      gamma-lactones in ionic liquids.
AB  - A highly efficient and mild palladium-catalyzed, one-pot, four-step cascade
      annulation has been developed to afford functionalized beta- and gamma-lactones
      in moderate to good yields with high regio- and diastereoselectivities in ionic
      liquids. The employment of ionic liquids under mild reaction conditions makes
      this transformation green and practical. Especially, this reaction provided a
      novel and convenient methodology for the construction of naturally occurring
      biologically active beta- and gamma-lactones. 

PMID- 24866485
TI  - Involve both genetic and environmental factors to build monkey models of mental
      disorders.

PMID- 24866484
TI  - Animal models to study Mycobacterium tuberculosis and HIV co-infection.
AB  - Mycobacterium tuberculosis (M.tb) and human immunodeficiency virus (HIV) co
      infection has become a public health issue worldwide. Up to now, there have been
      many unresolved issues either in the clinical diagnosis and treatment of M.tb/HIV
      co-infection or in the basic understanding of the mechanisms for the impairments
      to the immune system by interactions of these two pathogens. One important reason
      for these unsolved issues is the lack of appropriate animal models for the study
      of M.tb/HIV co-infection. This paper reviews the recent development of research
      on the animal models of M.tb/HIV co-infection, with a focus on the non-human
      primate models. 

PMID- 24866486
TI  - Non-human primate models in drug addiction deserve more attention.

PMID- 24866488
TI  - Parameter comparison of white matter diffusion tensor imaging (DTI) in rhesus
      macaques (Macaca mulatta).
AB  - In this study, we analyzed diffusion tensor imaging (DTI) results of brain white
      matter in rhesus macaques (Macaca mulatta) with four different parameter settings
      and found that the sequence A (b=1 000 s/mm(2), spatial resolution=1.25 mm*1.25
      mm* 1.25 mm, numbers of direction=33, NSA=3) and B (b=800 s/mm(2), spatial
      resolution=1.25 mm*1.25 mm*1.25 mm, numbers of direction=33, NSA=3) could
      accurately track coarse fibers. The fractional anisotropy (FA) derived from
      sequence C (b=1 000s/mm(2), spatial resolution=0.55 mm*0.55 mm*2.5 mm, direction
      number=33, NSA=3) was too fuzzy to be used in tracking white matter fibers. By
      comparison, the high resolution and the FA with high contrast of gray matter and
      white matter derived from sequence D (b=800 s/mm(2), spatial resolution=1.0
      mm*1.0 mm *1.0 mm, numbers of direction=33, NSA=3) qualified in its application
      in tracking both thick and thin fibers, making it an optimal DTI setting for
      rhesus macaques. 

PMID- 24866487
TI  - A natural model of behavioral depression in postpartum adult female cynomolgus
      monkeys (Macaca fascicularis).
AB  - Postpartum depression (PPD) is a modified form of major depressive disorders
      (MDD) that can exert profound negative effects on both mothers and infants than
      MDD. Within the postpartum period, both mothers and infants are susceptible; but
      because PPD typically occurs for short durations and has moderate symptoms, there
      exists challenges in exploring and addressing the underlying cause of the
      depression. This fact highlights the need for relevant animal models. In the
      present study, postpartum adult female cynomolgus monkeys (Macaca fascicularis)
      living in breeding groups were observed for typical depressive behavior. The
      huddle posture behavior was utilized as an indicator of behavioral depression
      postpartum (BDP) as it has been established as the core depressive-like behavior
      in primates. Monkeys were divided into two groups: A BDP group (n=6), which were
      found to spend more time huddling over the first two weeks postpartum than other
      individuals that formed a non-depression control group (n=4). The two groups were
      then further analyzed for locomotive activity, stressful events, hair cortisol
      levels and for maternal interactive behaviors. No differences were found between
      the BDP and control groups in locomotive activity, in the frequencies of
      stressful events experienced and in hair cortisol levels. These findings
      suggested that the postpartum depression witnessed in the monkeys was not related
      to external factors other than puerperium period. Interestingly, the BDP monkeys
      displayed an abnormal maternal relationship consisting of increased infant
      grooming. Taken together, these findings suggest that the adult female cynomolgus
      monkeys provide a natural model of behavioral postpartum depression that holds a
      number of advantages over commonly used rodent systems in PPD modeling. The
      cynomolgus monkeys have a highly-organized social hierarchy and reproductive
      characteristics without seasonal restriction-similar to humans-as well as much
      greater homology to humans than rodents. As such, this model may provide a
      greater translational efficiency and research platform for systematically
      investigating the etiology, treatment, prevention of PPD. 

PMID- 24866489
TI  - Replication potentials of HIV-1/HSIV in PBMCs from northern pig-tailed macaque
      (Macaca leonina).
AB  - The northern pig-tailed macaque (Macaca leonina) has been identified as an
      independent species of Old World monkey, and we previously found that PBMCs from
      M. leonina were susceptible to human immunodeficiency virus type 1 (HIV-1), which
      may be due to the absence of a TRIM5 protein restricting HIV-1 replication. Here
      we investigated the infection potentials of six laboratory adapted HIV-1 strains
      and three primary HIV-1 isolates in PBMCs from M. leonina. The results indicate
      that these strains are characterized by various but low replication levels, and
      among which, HIV-1NL4-3 shows the highest replication ability. Based on the
      abundant evidence of species-specific interactions between restriction factors
      APOBEC3 and HIV/SIV-derived Vif protein, we subsequently examined the replication
      potentials of vif-substituted HIV-1 (HSIV) in M. leonina PBMCs. Notably, HSIV
      vifmac and stHIV-1SV chimeras, two HIV-1NL4-3-derived viruses encoding the viral
      infectivity factor (Vif) protein from SIVmac239, replicated robustly in cells
      from M. leonina, which suggests that HSIV could effectively antagonize the
      antiviral activity of APOBEC3 proteins expressed in cells of M. leonina.
      Therefore, our data demonstrate that M. leonina has the potential to be developed
      into a promising animal model for human AIDS. 

PMID- 24866491
TI  - Dominance hierarchy and social relationships in a group of captive black-and
      white snub-nosed monkeys (Rhinopithecus bieti).
AB  - Different types of dominance hierarchies reflect different social relationships
      in primates. In this study, we clarified the hierarchy and social relationships
      in a one-male unit of captive Rhinopithecus bieti observed between August 1998
      and March 1999. Mean frequency of agonistic behaviour among adult females was
      0.13 interactions per hour. Adult females exhibited a linear hierarchy with a
      reversal of 10.9%, indicating an unstable relationship; therefore, R. bieti
      appears to be a relaxed/tolerant species. The lack of a relationship between the
      agonistic ratio of the adult male towards adult females and their ranks indicated
      that males did not show increased aggression towards low-ranking females.
      Differentiated female affiliative relationships were loosely formed in terms of
      the male, and to some extent influenced by female estrus, implying that
      relationships between the male and females is influenced by estrus and not rank
      alone. A positive correlation between the agonistic ratio of adult females and
      their ranks showed that the degree to which one female negatively impacted others
      decreased with reduction in rank. Similarly, a positive correlation between the
      agonistic ratio of females and differences in rank suggests that a female had
      fewer negative effects on closely ranked individuals than distantly ranked ones.
      These data indicate that rank may influence relationships between females. A
      steeper slope of regression between the agonistic ratio and inter-female rank
      differences indicated that the extent of the power difference in high-ranking
      females exerting negative effects on low-ranking ones was larger during the
      mating season than the birth season, suggesting that rank may influence the
      mating success of females. 

PMID- 24866492
TI  - Influence of dominance rank and affiliation relationships on self-directed
      behavior in female Tibetan macaques (Macaca thibetana).
AB  - Self-directed behavior (SDB) is characterized as an indicator of anxiety,
      frustration and stress in nonhuman primates. In this study, we collected self
      directed behavior data from one group of free-ranging Tibetan macaques (Macaca
      thibetana) at Mt. Huangshan, China (September 2012-May 2013) using a combination
      of behavioral sampling methods including focal animal sampling, behavioral
      sampling, continuous sampling and instantaneous sampling. Our results showed that
      females engaged in significantly higher rates of self-directed behavior when they
      were in proximity to dominant individuals compared to subordinate ones. Conflict
      losers significantly increased their SDB rates after agonistic episodes,
      indicating that SDB might also serve as an index of anxiety in M. thibetana. We
      further found that females significantly increased their SDB rates when focal
      individual was proximity to weakly affiliation relationship higher rank members
      than to strongly affiliation relationship higher rank members. If conflicts were
      not reconciled, the postconflict SDB rates of losers were higher when they stayed
      with strongly affiliation opponents; if conflicts were reconciled, victims of
      strongly affiliation relationships opponents engaged in more SDB rates before
      reconciliation than after reconciliation, while victims of moderately affiliation
      relationships opponents did not engaged in more SDB rates before reconciliation
      than after reconciliation. We conclude that both of dominance rank and
      affiliation relationships might both influence the SDB rates of female Tibetan
      macaques significantly, suggesting that SDB is not only an index of anxiety in
      Tibetan macaques, but also can provide a new insight into evaluation of social
      relationships between individuals. 

PMID- 24866490
TI  - Analysis of immunoglobulin, complements and CRP levels in serum of captive
      northern pig-tailed macaques (Macaca leonina).
AB  - The northern pig-tailed macaque (NPM,Macaca leonina) has become a widely used
      animal model in biomedical research. In this study, we measured serum
      immunoglobulin IgG, IgM, IgA, complement C3, C4 and CRP levels in 3-11 year old
      captive northern pig-tailed macaques using HITACHI 7600-20 automated chemistry
      analyzer in order to determine the influences of age and gender on these items.
      The results showed that serum IgA, IgM, C3 and C4 levels were not correlated with
      age (P>0.05), while serum IgG levels increased progressively with age
      (r=0.202;P=0.045). Serum IgG, IgA, IgM and C3 levels were higher in females than
      in males (P<0.05). Moreover, serum C3 concentration was both positively and
      strongly correlated with that of C4 (r=0.700; P<0.0001). This study provides
      basic serum immunoglobulin and complement data of captive northern pig-tailed
      macaques, which may prove useful for future breeding efforts and biomedical
      research.

PMID- 24866493
TI  - Male Tibetan macaques'(Macaca thibetana) choice of infant bridging partners.
AB  - Adult male Tibetan (Macaca thibetana), Barbary (M. sylvanus), and stump-tailed
      macaques (M. arctoides) engage in bridging, a ritualized infant-handling
      behavior. Previous researchers found a bias toward the use of male infants for
      this behavior, but its function is debated. Explanations include three
      hypotheses: paternal care, mating effort, and agonistic buffering. We studied a
      group of habituated, provisioned Tibetan macaques to test whether adult males'
      affiliative relationships with females predicted their use of an infant for
      bridging. We also examined biases for sex, age, and individual in males' choice
      of bridging infant. We collected data via all occurrences, focal animal, and scan
      methods, from August to September 2011 at the Valley of the Wild Monkeys, China.
      We found that male infants were significantly preferred over females for
      bridging, but of three male infants in the group, only one was used by all males,
      while one male infant was used less often than expected. Adult males had females
      they were significantly more likely to be proximate to and/or to groom, but these
      corresponded to the mother of the bridging infant for only one male. Our results
      are most consistent with the agonistic buffering hypothesis: lower-ranked males
      used the alpha male's preferred bridging infant in an attempt to regulate their
      interactions with the alpha. 

PMID- 24866494
TI  - Effects of tsaoko (Fructus tsaoko) cultivating on tree diversity and canopy
      structure in the habitats of eastern hoolock gibbon (Hoolock leuconedys).
AB  - In this study, the quadrat method was used to study the effects of tsaoko
      (Fructus tsaoko) plantation on tree diversity and canopy structure of two natural
      habitats of eastern hoolock gibbon (Hoolock leuconedys): Nankang (characterized
      by extensive tsaoko plantation) and Banchang (relatively well reserved and
      without tsaoko plantation). Totally, 102 tree species from 25 families and 16
      woody liana species from 10 families were recorded in Nankang, whereas 108 tree
      species from 30 families and 17 woody liana species from 12 families were
      recorded in Banchang. Although the tree species between two habitats is
      different, both habitats are characterized by enriched food resources for eastern
      hoolock gibbons, sharing similar dominant plant families. Due to tsaoko
      plantation, tree density proportion and diversity of forest layerI (>20 m) in
      Nankang were both significantly decreased, but the tree density of layerII (10-20
      m) increased. Likewise, in conjunction with these behavioral observations, we
      also address potential impacts of tsaoko plantation on the behavior of eastern
      hoolock gibbon. 

PMID- 24866495
TI  - Positively selected genes of the Chinese tree shrew (Tupaia belangeri chinensis)
      locomotion system.
AB  - While the recent release of the Chinese tree shrew (Tupaia belangeri chinensis)
      genome has made the tree shrew an increasingly viable experimental animal model
      for biomedical research, further study of the genome may facilitate new insights
      into the applicability of this model. For example, though the tree shrew has a
      rapid rate of speed and strong jumping ability, there are limited studies on its
      locomotion ability. In this study we used the available Chinese tree shrew genome
      information and compared the evolutionary pattern of 407 locomotion system
      related orthologs among five mammals (human, rhesus monkey, mouse, rat and dog)
      and the Chinese tree shrew. Our analyses identified 29 genes with significantly
      high omega (Ka/Ks ratio) values and 48 amino acid sites in 14 genes showed
      significant evidence of positive selection in the Chinese tree shrew. Some of
      these positively selected genes, e.g. HOXA6 (homeobox A6) and AVP (arginine
      vasopressin), play important roles in muscle contraction or skeletal
      morphogenesis. These results provide important clues in understanding the genetic
      bases of locomotor adaptation in the Chinese tree shrew. 

PMID- 24866497
TI  - Surgical management of medically refractory epilepsy due to early childhood
      stroke.
AB  - OBJECT.: The risk of developing epilepsy after perinatal stroke, hypoxic/ischemic
      injury, and intracerebral hemorrhage is significant, and seizures may become
      medically refractory in approximately 25% of these patients. Surgical management
      can be difficult due to multilobar or bilateral cortical injury, nonfocal or
      poorly lateralizing video electroencephalography (EEG) findings, and limited
      functional reserve. In this study the authors describe the surgical approaches,
      seizure outcomes, and complications in patients with epilepsy due to vascular
      etiologies in the perinatal period and early infancy. METHODS: The records were
      analyzed of 19 consecutive children and adults with medically refractory epilepsy
      and evidence of perinatal arterial branch occlusions, hypoxic/ischemic insult, or
      hemorrhagic strokes, who underwent surgery at the Comprehensive Epilepsy Center
      of Beth Israel Medical Center and St. Luke's-Roosevelt Hospital Center.
      Preoperative findings including MRI, video EEG, functional MRI, and
      neuropsychological testing were analyzed. The majority of patients underwent
      staged operations with invasive mapping, and all patients had either extra- or
      intraoperative functional mapping. RESULTS: In 7 patients with large
      porencephalic cysts due to major arterial branch occlusions, periinsular
      functional hemispherotomy was performed in 4 children, and in 3 patients,
      multilobar resections/disconnections were performed, with 1 patient undergoing
      additional resections 3 years after initial surgery due to recurrence of
      seizures. All of these patients have been seizure free (Engel Class IA) after a
      mean 4.5-year follow-up (range 15-77 months). Another 8 patients had
      intervascular border-zone ischemic infarcts and encephalomalacia, and in this
      cohort 2 hemispherotomies, 5 multilobar resections/disconnections, and 1 focal
      cortical resection were performed. Seven of these patients remain seizure free
      (Engel Class IA) after a mean 4.5-year follow-up (range 9-94 months), and 1
      patient suffered a single seizure after 2.5 years of seizure freedom (Engel Class
      IB, 33-month follow-up). In the final 4 patients with vascular malformation
      associated hemorrhagic or ischemic infarction in the perinatal period, a
      hemispherotomy was performed in 1 case, multilobar resections in 2 cases, and in
      1 patient a partial temporal lobectomy was performed, followed 6 months later by
      a complete temporal and occipital lobectomy due to ongoing seizures. All of these
      patients have had seizure freedom (Engel Class IA) with a mean follow-up of 4.5
      years (range 10-80 months). Complications included transient monoparesis or
      hemiparesis in 3 patients, transient mutism in 1 patient, infection in 1 patient,
      and a single case of permanent distal lower-extremity weakness. Transient mood
      disorders (depression and anxiety) were observed in 2 patients and required
      medical/therapeutic intervention. CONCLUSIONS: Epilepsy surgery is effective in
      controlling medically intractable seizures after perinatal vascular insults.
      Seizure foci tend to be widespread and rarely limited to the area of injury
      identified through neuroimaging, with invasive monitoring directing multilobar
      resections in many cases. Long-term functional outcomes have been good in these
      patients, with significant improvements in independence, quality of life,
      cognitive development, and motor skills, despite transient postoperative
      monoparesis or hemiparesis and occasional mood disorders.

PMID- 24866498
TI  - Immediate effects of varying cadence in bicycle ergometry on characteristics of
      gait and lower extremity motor activity in frail older adults.
AB  - AIM: This study examined the immediate effects of a 5-min pedaling period with
      varying cadence (VC) on various dimensions of gait function in frail older
      adults. METHODS: Twenty frail older adults (mean age 77.2 years) were randomly
      assigned to one of two groups: the VC group or the constant cadence (CC) group.
      Each group performed bicycle ergometry for 5 min at 20 W. The CC group pedaled
      continuously at a CC of 50 rpm, while the VC group pedaled continuously at
      cadences of 45, 55, 65, 55, and 45 rpm, in this order, changing cadence every 60
      s. Immediately before and after bicycle ergometry, the following measurements
      were carried out: gait performance, muscle activity (electromyographic analysis),
      and knee motion analysis. RESULTS: CC did not significantly affect any of the
      measured parameters. In contrast, the VC group showed improvement in all three
      parameters: an increase in normal gait speed and cadence (p < 0.01), a reduction
      in the activation period (p < 0.04) and CI-THIGH (antagonistic coactivation time
      between knee flexor and extensor muscles, p < 0.05), and an increase in maximum
      knee extension angular velocity (p < 0.01). CONCLUSION: A short period of VC
      bicycle ergometry with low work intensity was effective in immediately improving
      gait function in frail older adults.

PMID- 24866496
TI  - Safety and metabolic outcomes of resveratrol supplementation in older adults:
      results of a twelve-week, placebo-controlled pilot study.
AB  - Resveratrol has been found to have potent antioxidant, anti-inflammatory, and
      anticarcinogenic effects. The safety and efficacy of resveratrol supplementation
      in older adults are currently unknown. We conducted a double-blind, randomized,
      placebo-controlled trial to examine the safety and metabolic outcomes in 32
      overweight, older adults (mean age, 73+/-7years). Participants were randomized
      into one of three treatment groups: (1) placebo, (2) moderate dose resveratrol
      (300mg/day), and (3) high dose resveratrol (1000mg/day). Both resveratrol and
      placebo were orally ingested in capsule form twice daily for 90days. Blood
      chemistry values remained within the normal range, and there were no significant
      differences in the number of participants reporting adverse events across
      conditions. Compared to placebo, glucose levels were significantly lower at post
      treatment among participants randomized to both resveratrol conditions, with and
      without adjustment for the corresponding baseline values (ps<0.05). Glucose
      values of participants in the treatment groups, however, were not significantly
      different from baseline levels. These findings suggest that short-term
      resveratrol supplementation at doses of 300mg/day and 1000mg/day does not
      adversely affect blood chemistries and is well tolerated in overweight, older
      individuals. These findings support the study of resveratrol for improving cardio
      metabolic health in older adults in larger clinical trials. 

PMID- 24866500
TI  - Three commercial antibodies against alpha1-adrenergic receptor subtypes lack
      specificity in paraffin-embedded sections of murine tissues.
AB  - We tested the specificity of three commercially available antibodies (AB) against
      individual alpha1-adrenergic receptor subtypes (alpha1-ARST). We used these ABs
      to localize the alpha1-ARST proteins by immunohistochemistry in paraffin-embedded
      murine tissues. The specificity of the ABs was tested by comparing staining
      patterns in tissues from wild-type mice with those in corresponding tissues from
      mice with gene-targeted disruption of the respective alpha1-ARST, one of the most
      rigorous negative controls. None of the tested ABs proved to be specific for the
      indicated target antigen. We conclude that the tested ABs are unsuitable for
      immunohistochemistry in paraffin-embedded murine tissues.

PMID- 24866501
TI  - A pharmacological paradox: may a neutral antagonist shift an agonist
      concentration-response curve to the left?
AB  - It is generally accepted that the presence of a competitive antagonist shifts an
      agonist concentration-response curve to the right. However, this may not always
      be the case: The concentration-response curve of an inverse receptor agonist may
      be shifted to the left by a neutral antagonist; a condition, which can be
      hypothetically explained by the assumption of both negative cooperativity of
      dimeric receptors plus a receptor reserve. 

PMID- 24866502
TI  - Total synthesis of taiwaniadducts B, C, and D.
AB  - The first total syntheses of taiwaniadducts B, C, and D have been accomplished.
      Two diterpenoid segments were prepared with high enantiopurity, both through Ir
      catalyzed asymmetric polyene cyclization. A sterically demanding intermolecular
      Diels-Alder reaction promoted by Er(fod)3 assembled the scaffold of
      taiwaniadducts B and C. A carbonyl-ene cyclization forged the cage motif of
      taiwaniadduct D at a late stage, providing over 200 mg of this compound. 

PMID- 24866499
TI  - Silymarin ameliorates memory deficits and neuropathological changes in mouse
      model of high-fat-diet-induced experimental dementia.
AB  - A huge body evidences suggest that obesity is the single great risk factor for
      the development of dementia. Recently, silymarin, a flavonoid, clinically in use
      as a hepatoprotectant, has been reported to prevent amyloid beta-induced memory
      impairment by reducing oxidative stress and inflammation in mice brain. However,
      its potential in high-fat-diet (HFD)-induced dementia has not yet been
      investigated. Therefore, the present study is designed to explore the role of
      silymarin in HFD-induced experimental dementia in mice. Morris water maze test
      was employed to assess learning and memory. Various biochemical estimations
      including brain acetylcholinerstarse activity (AchE), thiobarbituric acid
      reactive species (TBARS) level, reduced glutathione level (GSH), nirate/nitrite,
      and myeloperoxidase (MPO) activity were measured. Serum cholesterol level was
      also determined. HFD significantly impaired the cognitive abilities, along with
      increasing brain AchE, TBARS, MPO, nitrate/nitrite, and serum cholesterol levels.
      Marked reduction of brain GSH levels was observed. On the contrary, silymarin
      significantly reversed HFD-induced cognitive deficits and the biochemical
      changes. The present study indicates strong potential of silymarin in HFD-induced
      experimental dementia. 

PMID- 24866503
TI  - Differential expression of stromal aromatase in obese females is regulated by DNA
      methylation.
AB  - Obesity increases the incidence, progression and mortality of breast cancer among
      postmenopausal females. This is partly due to excessive estrogen production in
      the adipose tissue of obese females. Aromatase is a key enzyme in estrogen
      biosynthesis. In the current study, the tensional force-triggered inducibility of
      aromatase expression was observed to vary in ASCs isolated from different disease
      free individuals. In addition, this phenomenon was associated with the activation
      of the aromatase PII promoter and its DNA methylation load. These findings
      highlight the impact of tensional forces on estrogen biosynthesis in obese
      females. 

PMID- 24866504
TI  - Spatio-temporal patterns in rhizosphere oxygen profiles in the emergent plant
      species Acorus calamus.
AB  - Rhizosphere oxygen profiles are the key to understanding the role of wetland
      plants in ecological remediation. Though in situ determination of the rhizosphere
      oxygen profiles has been performed occasionally at certain growing stages within
      days, comprehensive study on individual roots during weeks is still missing.
      Seedlings of Acorus calamus, a wetland monocot, were cultivated in silty sediment
      and the rhizosphere oxygen profiles were characterized at regular intervals,
      using micro-optodes to examine the same root at four positions along the root
      axis. The rhizosphere oxygen saturation culminated at 42.9% around the middle
      part of the root and was at its lowest level, 3.3%, at the basal part of the root
      near the aboveground portion. As the plant grew, the oxygen saturation at the
      four positions remained nearly constant until shoot height reached 15 cm. When
      shoot height reached 60 cm, oxygen saturation was greatest at the point halfway
      along the root, followed by the point three-quarters of the way down the root,
      the tip of the root, and the point one-quarter of the way down. Both the internal
      and rhizosphere oxygen saturation steadily increased, as did the thickness of
      stably oxidized microzones, which ranged from 20 um in younger seedlings to a
      maximum of 320 um in older seedlings. The spatial patterns of rhizosphere oxygen
      profiles in sediment contrast with those from previous studies on radial oxygen
      loss in A. calamus that used conventional approaches. Rhizosphere oxygen
      saturation peaked around the middle part of roots and the thickness of stably
      oxidized zones increased as the roots grew. 

PMID- 24866506
TI  - Effects of sevoflurane anesthesia on righting reflex and hemolymph gas analysis
      variables for Chilean rose tarantulas (Grammostola rosea).
AB  - OBJECTIVE: To determine the safety, efficacy, and effects on hemolymph gas
      analysis variables of sevoflurane anesthesia in Chilean rose tarantulas
      (Grammostola rosea). ANIMALS: 12 subadult Chilean rose tarantulas of unknown sex.
      PROCEDURES: Spiders were anesthetized in a custom chamber with sevoflurane (5% in
      oxygen [1.0 L/min]), then allowed to recover in 100% oxygen. Righting reflex was
      evaluated every 3 minutes during anesthesia to determine time to anesthetic
      induction and recovery. Hemolymph samples were collected from an intracardiac
      location prior to and after induction of anesthesia and evaluated to determine
      various gas analysis variables. RESULTS: Mean +/- SD induction and recovery times
      were 16 +/- 5.91 minutes and 29 +/- 21.34 minutes, respectively. Significant
      differences were detected for Po2, base excess, and glucose and ionized magnesium
      concentrations between hemolymph samples obtained before anesthesia and those
      obtained after induction of anesthesia. CONCLUSIONS AND CLINICAL RELEVANCE
      Results of this study suggested that the use of sevoflurane as an anesthetic
      agent for Chilean rose tarantulas was safe and effective. Various hemolymph
      sample gas analysis values changed during anesthesia.

PMID- 24866507
TI  - Pharmacokinetics of hydromorphone hydrochloride after intravenous and
      intramuscular administration of a single dose to American kestrels (Falco
      sparverius).
AB  - OBJECTIVE: To determine the pharmacokinetics of hydromorphone hydrochloride after
      IV and IM administration in American kestrels (Falco sparverius). ANIMALS: 12
      healthy adult American kestrels. PROCEDURES: A single dose of hydromorphone (0.6
      mg/kg) was administered IM (pectoral muscles) and IV (right jugular vein); the
      time between IM and IV administration experiments was 1 month. Blood samples were
      collected at 5 minutes, 1 hour, and 3 hours (n = 4 birds); 0.25, 1.5, and 9 hours
      (4); and 0.5, 2, and 6 hours (4) after drug administration. Plasma hydromorphone
      concentrations were determined by means of liquid chromatography with mass
      spectrometry, and pharmacokinetic parameters were calculated with a
      noncompartmental model. Mean plasma hydromorphone concentration for each time was
      determined with naive averaged pharmacokinetic analysis. RESULTS: Plasma
      hydromorphone concentrations were detectable in 2 and 3 birds at 6 hours after IM
      and IV administration, respectively, but not at 9 hours after administration. The
      fraction of the hydromorphone dose absorbed after IM administration was 0.75. The
      maximum observed plasma concentration was 112.1 ng/mL (5 minutes after
      administration). The terminal half-life was 1.25 and 1.26 hours after IV and IM
      administration, respectively. CONCLUSION AND CLINICAL RELEVANCE: Results
      indicated hydromorphone hydrochloride had high bioavailability and rapid
      elimination after IM administration, with a short terminal half-life, rapid
      plasma clearance, and large volume of distribution in American kestrels. Further
      studies regarding the effects of other doses, other administration routes,
      constantrate infusions, and slow release formulations on the pharmacokinetics of
      hydromorphone hydrochloride and its metabolites in American kestrels may be
      indicated.

PMID- 24866508
TI  - Canine Brief Pain Inventory scores for dogs with osteoarthritis before and after
      administration of a monoclonal antibody against nerve growth factor.
AB  - OBJECTIVE: To determine changes in Canine Brief Pain Inventory scores for dogs
      with osteoarthritis after administration of a monoclonal antibody (mAb) against
      nerve growth factor (NGF) that was modified by use of a proprietary process for
      administration to dogs. ANIMALS: 11 adult dogs. PROCEDURES: Dogs received the
      anti-NGF mAb (0.2 mg/kg, IV) at various evaluation times during the study period;
      at other evaluation times, dogs received an equivalent volume of PBS solution IV.
      Owners determined Canine Brief Pain Inventory pain severity (PS) and pain
      interference (PI) scores immediately before (baseline) and 2, 4, and 6 weeks
      after administration of the anti-NGF mAb; owners were unaware of the evaluation
      time at which the mAb had been administered. RESULTS: Compared with baseline PS
      scores (median, 4.75; range, 0.75 to 8.5), dogs had significantly lower PS scores
      2 weeks (median, 3; range, 1 to 5.5) and 4 weeks (median, 2.25; range, 0.25 to
      7.25) after administration of anti-NGF mAb. Compared with baseline PI scores
      (median, 5.33; range, 1.17 to 9.33), dogs had significantly lower PI scores 2
      weeks (median, 3; range, 0.67 to 6.83) and 4 weeks (median, 3.33; range, 0.67 to
      6.67) after administration of anti-NGF mAb. The PS and PI scores 6 weeks after
      mAb administration were lower than baseline scores, although values were not
      significantly different. CONCLUSIONS AND CLINICAL RELEVANCE: Results of this
      study suggested the evaluated anti-NGF mAb decreased PS and PI scores for 4 weeks
      after administration. This treatment may be effective for alleviation of signs of
      pain in dogs with osteoarthritis for up to 4 weeks.

PMID- 24866509
TI  - Evaluation of four methods for inducing death during slaughter of American
      alligators (Alligator mississippiensis).
AB  - OBJECTIVE: To evaluate physical methods for inducing death during the slaughter
      of American alligators (Alligator mississippiensis). ANIMALS: 24 captive hatched
      and-reared American alligators. PROCEDURES: Baseline electroencephalograms (EEGs)
      were obtained for awake and anesthetized alligators. Corneal reflex, spontaneous
      blinking, and EEGs were evaluated after severance of the spinal cord, severance
      of the spinal cord followed by pithing of the brain, application of a penetrating
      captive bolt, or application of a nonpenetrating captive bolt (6
      alligators/group). RESULTS: Overall, alligators subjected to spinal cord
      severance alone differed from those subjected to the other techniques. Spinal
      cord severance alone resulted in postprocedure EEG power values greater than
      those in anesthetized alligators, whereas the postprocedure EEG power values were
      isoelectric for the other 3 techniques. Corneal reflex and spontaneous blinking
      were absent in all alligators immediately after application of a penetrating or
      nonpenetrating captive bolt. One of 6 alligators had a corneal reflex up to 1
      minute after pithing, but all others within that group had immediate cessation of
      reflexes after pithing. Mean time to loss of spontaneous blinking and corneal
      reflex for alligators subjected to spinal cord severance alone was 18 minutes
      (range, 2 to 37 minutes) and 54 minutes (range, 34 to 99 minutes), respectively.
      CONCLUSIONS AND CLINICAL RELEVANCE: Spinal cord severance followed by pithing of
      the brain and application of a penetrating or nonpenetrating captive bolt
      appeared to be humane and effective techniques for inducing death in American
      alligators, whereas spinal cord severance alone was not found to be an
      appropriate method.

PMID- 24866510
TI  - Use of an inverse dynamics method to describe the motion of the canine pelvic
      limb in three dimensions.
AB  - OBJECTIVE: To use an inverse dynamics method to describe the motion of the canine
      pelvic limb in 3 dimensions. ANIMALS: 6 healthy adult dogs. PROCEDURES: For each
      dog, 16 anatomic and tracking markers were used to define the center of rotation
      for the pelvic limb joints and a kinematic model was created to describe the
      motion of the pelvic limb. Kinetic, kinematic, and morphometric data were
      combined so that an inverse dynamics method could be used to define angular
      displacement, joint moment, and power of the hip, stifle, and tibiotarsal (hock)
      joints in the sagittal, frontal, and transverse planes. RESULTS: Movement and
      energy patterns were described for the hip, stifle, and hock joints in the
      sagittal, frontal, and transverse planes. CONCLUSIONS AND CLINICAL RELEVANCE:
      Knowledge of the 3-D movement of the pelvic limb can be used to better understand
      its motion, moment, and energy patterns in healthy dogs and provide a referent
      with which gaits of dogs with pelvic limb injuries before and after surgical
      repair or rehabilitation can be compared and characterized. This information can
      then be used to guide decisions regarding treatment options for dogs with pelvic
      limb injuries.

PMID- 24866511
TI  - Use of an inverse dynamics method to compare the three-dimensional motion of the
      pelvic limb among clinically normal dogs and dogs with cranial cruciate ligament
      deficient stifle joints following tibial plateau leveling osteotomy or lateral
      fabellar-tibial suture stabilization.
AB  - OBJECTIVE: To compare the 3-D motion of the pelvic limb among clinically normal
      dogs and dogs with cranial cruciate ligament (CCL)-deficient stifle joints
      following tibial plateau leveling osteotomy (TPLO) or lateral fabellar-tibial
      suture (LFS) stabilization by use of an inverse dynamics method. ANIMALS: 6
      clinically normal dogs and 19 dogs with CCL-deficient stifle joints that had
      undergone TPLO (n = 13) or LFS (6) stabilization at a mean of 4 and 8 years,
      respectively, prior to evaluation. PROCEDURES: For all dogs, an inverse dynamics
      method was used to describe the motion of the pelvic limbs in the sagittal,
      frontal, and transverse planes. Motion and energy patterns for the hip, stifle,
      and tibiotarsal (hock) joints in all 3 planes were compared among the 3 groups.
      RESULTS: Compared with corresponding variables for clinically normal dogs, the
      hip joint was more extended at the beginning of the stance phase in the sagittal
      plane for dogs that had a TPLO performed and the maximum power across the stifle
      joint in the frontal plane was greater for dogs that had an LFS procedure
      performed. Otherwise, variables in all planes were similar among the 3 groups.
      CONCLUSIONS AND CLINICAL RELEVANCE: Gait characteristics of the pelvic limb did
      not differ between dogs that underwent TPLO and dogs that underwent an LFS
      procedure for CCL repair and were similar to those of clinically normal dogs.
      Both TPLO and LFS successfully provided long-term stabilization of CCL-deficient
      stifle joints of dogs with minimal alterations in gait.

PMID- 24866512
TI  - Comparison of cardiac output determined by an ultrasound velocity dilution
      cardiac output method and by the lithium dilution cardiac output method in
      juvenile horses with experimentally induced hypovolemia.
AB  - OBJECTIVE: To assess the accuracy of an ultrasound velocity dilution cardiac
      output (UDCO) method, compared with that of the lithium dilution cardiac output
      (LiDCO) method, for determination of cardiac output (CO) in juvenile horses with
      experimentally induced hypovolemia. ANIMALS: 12 anesthetized 2- to 6-month-old
      horses. PROCEDURES: For each anesthetized horse, CO was determined by the LiDCO
      and UDCO methods prior to any intervention (baseline state), after withdrawal of
      approximately 40% of the horse's blood volume (low CO state), after maintenance
      of hypovolemia and infusion of norepinephrine until mean arterial blood pressure
      was equal to baseline value (high CO state), and after further infusion of
      norepinephrine and back-transfusion of withdrawn blood (posttransfusion state).
      For each of the 4 hemodynamic situations, CO and calculated cardiac index (CI)
      values were obtained by each method in duplicate (8 pairs of measurements/horse);
      mean values for each horse and overall mean values across all horses were
      calculated. Agreement between CI determined by each method (96 paired values) was
      assessed by Bland-Altman analysis. RESULTS: For the UDCO method-derived CI
      measurements among the 12 horses, mean +/- SD bias was -4 +/- 11.3 mL/kg/min (95%
      limits of agreement, -26.1 to 18.2 mL/kg/min) and mean relative bias was -10.4 +/
      21.5% (95% limits of agreement, -52.6% to 31.8%). CONCLUSIONS AND CLINICAL
      RELEVANCE: Results indicated that, compared with the LiDCO method, the UDCO
      method has acceptable clinical usefulness for determination of CO in foals.

PMID- 24866513
TI  - Effects of physiologic concentrations of l-lysine on in vitro replication of
      feline herpesvirus 1.
AB  - OBJECTIVE: To evaluate the effects of various concentrations of l-lysine on in
      vitro replication of feline herpesvirus 1 (FHV-1). SAMPLE: Cultures of Crandell
      Rees feline kidney (CRFK) cells. PROCEDURES: CRFK cells were inoculated with FHV
      1 and maintained in media with 20 combinations of l-arginine and l-lysine
      concentrations. Changes in cell viability were monitored by continuous
      measurement of electrical impedance of cultured cells and by observation of viral
      cytopathic effects. Viral load was determined by use of quantitative PCR assay in
      supernatants obtained from infected cultures at specified time points. RESULTS:
      Increases in l-lysine concentration had no effect on the kinetics of cell death
      in FHV-1-infected cultures. There was also no significant effect (r(2) < 0.1) on
      viral DNA load for l-arginine concentrations >= 12 MUg/mL There was a significant
      effect of increases in l-lysine concentration on viral DNA load in media
      supplemented with 6 MUg of l-arginine/mL (mean +/- SD slope, -4,641 +/- 1,626
      units; adjusted r(2) = 0.45). However, the difference between the lowest (1 *
      10(6.28) copies/MUL) and highest (1 * 10(6.86) copies/MUL) FHV-1 DNA load in
      these media was < 1 logarithm. CONCLUSIONS AND CLINICAL RELEVANCE: The difference
      in FHV-1 DNA load was unlikely to be biologically important. Various l-lysine
      concentrations did not inhibit in vitro replication of FHV-1 at l-arginine
      concentrations sufficient to maintain cell growth. This conclusion was consistent
      with results of other studies in which investigators have not detected a
      consistently beneficial effect when l-lysine is administered to FHV-1-infected
      cats.

PMID- 24866514
TI  - Reproducibility and feasibility of acoustoelastography in the superficial digital
      flexor tendons of clinically normal horses.
AB  - OBJECTIVE: To evaluate the feasibility and repeatability of in vivo measurement
      of stiffness gradients by means of acoustoelastography in the superficial digital
      flexor tendons (SDFTs) of clinically normal horses. ANIMALS: 15 clinically normal
      horses. PROCEDURES: For each horse, stiffness gradient index and dispersion
      values for SDFTs in both forelimbs were evaluated in longitudinal orientation by
      use of acoustoelastography at 3 sites (5, 10, and 15 cm distal to the accessory
      carpal bone) by 2 observers; for each observer, data were acquired twice per
      site. The left forelimb was always scanned before the right forelimb. Lifting of
      the contralateral forelimb with the carpus flexed during image acquisition
      resulted in the required SDFT deformation in the evaluated limb. Interobserver
      repeatability, intraobserver repeatability, and right-to-left limb symmetry for
      stiffness gradient index and dispersion values were evaluated. RESULTS: Stiffness
      gradient index and dispersion values for SDFTs at different locations as well as
      effects of age or sex did not differ significantly among the 15 horses.
      Interclass correlation coefficients for interobserver repeatability,
      intraobserver repeatability, and limb symmetry revealed good to excellent
      agreement (intraclass correlation coefficients, > 0.74). CONCLUSIONS AND CLINICAL
      RELEVANCE: Results indicated that acoustoelastography is a feasible and
      repeatable technique for measuring stiffness gradients in SDFTs in clinically
      normal horses, and could potentially be used to compare healthy and diseased
      tendon states.

PMID- 24866515
TI  - Kinetic analysis of 2-([(18)F]fluoro)-2-deoxy-d-glucose uptake in brains of
      anesthetized healthy dogs.
AB  - OBJECTIVE: To assess kinetic 2-([(18)F]fluoro)-2-deoxy-d-glucose ((18)FDG) uptake
      in the brain of anesthetized healthy adult dogs by use of positron emission
      tomography (PET) and to determine whether (18)FDG uptake differs among anatomic
      regions of the brain. ANIMALS: 5 healthy Beagles. PROCEDURES: Each isoflurane
      anesthetized dog was administered (18)FDG IV (dose range, 3.0 to 5.2 mCi), and
      PET data were acquired for 2 hours. A CT scan (without contrast agent
      administration) was performed to allow more precise neuroanatomic localization.
      Defined regions of interest within the brain were drawn on reconstructed image
      data. Standard uptake values (SUVs) for (18)FDG were calculated to generate time
      activity curves and determine time to peak uptake. RESULTS: Time-activity curve
      analysis identified 4 regional uptake patterns: olfactory, gray matter, white
      matter, and other (brainstem, cerebellum, and occipital and frontal regions). The
      highest maximum SUVs were identified in the olfactory bulbs and cerebral gray
      matter, and the lowest maximum SUV was identified in cerebral white matter. Mean
      time to peak uptake ranged from 37.8 minutes in white matter to 82.7 minutes in
      the olfactory bulbs. CONCLUSIONS AND CLINICAL RELEVANCE: Kinetic analysis of
      (18)FDG uptake revealed differences in uptake values among anatomic areas of the
      brain in dogs. These data provide a baseline for further investigation of (18)FDG
      uptake in dogs with immune-mediated inflammatory brain disease and suggest that
      (18)FDG-PET scanning has potential use for antemortem diagnosis without
      histologic analysis and for monitoring response to treatment. In clinical cases,
      a 1-hour period of PET scanning should provide sufficient pertinent data.

PMID- 24866517
TI  - Effect of intramammary administration of prednisolone on the blood-milk barrier
      during the immune response of the mammary gland to lipopolysaccharide.
AB  - OBJECTIVE: To investigate effects of intramammary administration of prednisolone
      on the immune response of mammary glands in cows. ANIMALS: 5 lactating Red
      Holsteins. PROCEDURES: Cows received a different intramammary infusion in each
      mammary gland (10 mg of prednisolone, 100 MUg of lipopolysaccharide [LPS], 100
      MUg of LPS and 10 mg of prednisolone, or saline [0.9% NaCl] solution). Milk
      samples were collected before (time 0) and 3, 6, 9, 12, 24, and 36 hours after
      treatment. Somatic cell count (SCC), lactate dehydrogenase (LDH) activity, and
      concentrations of serum albumin (SA) and tumor necrosis factor (TNF)-alpha in
      milk and mRNA expression of TNF-alpha, interleukin (IL)-8, and IL-1beta in milk
      somatic cells were analyzed. RESULTS: Saline solution or prednisolone did not
      change SCC, LDH activity, and SA and TNF-alpha concentrations in milk and mRNA
      expression of TNF-alpha, IL-1beta, and IL-8 in milk somatic cells. The SCC and
      TNF-alpha concentration in milk increased similarly in glands infused with LPS,
      independent of prednisolone administration. However, the increase of LDH activity
      and SA concentration in milk after LPS infusion was diminished by prednisolone
      administration. The mRNA expression of TNF-alpha, IL-8, and IL-1beta in milk
      somatic cells increased after LPS infusion and was unaffected by prednisolone.
      CONCLUSIONS AND CLINICAL RELEVANCE: Intramammary administration of prednisolone
      did not induce an immune response and did not change mRNA expression of TNF
      alpha, IL-8, and L-1beta during the response to intramammary administration of
      LPS. However, prednisolone reduced disruption of the blood-milk barrier. This
      could influence the severity and cure rate of mastitis.

PMID- 24866518
TI  - In vitro evaluation of anatomic landmarks for the placement of suture to achieve
      effective arytenoid cartilage abduction by means of unilateral cricoarytenoid
      lateralization in dogs.
AB  - OBJECTIVE: To evaluate anatomic landmarks to define the ideal suture placement
      location to achieve appropriate and consistent arytenoid cartilage abduction via
      unilateral cricoarytenoid lateralization (UCL) in dogs. SAMPLE: 6 cadaveric
      canine larynges. PROCEDURES: Laryngeal airway resistance (LAR) was determined for
      each specimen before (baseline) and after suture placements with the epiglottis
      open and closed. To achieve UCL, suture was placed through the cricoid cartilage
      just caudal to the cricoarytenoid articulation (suture placement position [SPP]
      1), one-fourth of the distance caudally between the cricoarytenoid and
      cricothyroid articulations (SPP 2), and three-fourths of the distance caudally
      between the cricoarytenoid and cricothyroid articulations (SPP 3). The LAR was
      again calculated after tensioning of each suture separately. RESULTS: With a
      closed epiglottis, median LAR was 30.0, 20.4, 11.4, and 3.3 cm H2O/L/s at
      baseline and SPPs 1, 2, and 3, respectively. After UCL at SPP 1, LAR with the
      epiglottis closed was not significantly different from that at baseline. With an
      open epiglottis, median LAR was 2.0, 0.4, 0.2, and 0.0 cm H2O/L/s at baseline and
      SPPs 1, 2, and 3, respectively. After UCL at SPPs 1, 2, or 3, LAR with an open
      epiglottis was significantly lower than that at baseline. CONCLUSIONS AND
      CLINICAL RELEVANCE: Results indicated that placement of suture through the
      cricoid cartilage at the caudal border of the cricoarytenoid articulation was
      appropriate to sufficiently reduce LAR without increasing the risk of aspiration
      pneumonia through overabduction of the arytenoid cartilage.

PMID- 24866519
TI  - CAD or MAD? Anger (not disgust) as the predominant response to pathogen-free
      violations of the divinity code.
AB  - The CAD triad hypothesis (Rozin, Lowery, Imada, & Haidt, 1999) stipulates that,
      cross-culturally, people feel anger for violations of autonomy, contempt for
      violations of community, and disgust for violations of divinity. Although the
      disgust-divinity link has received some measure of empirical support, the results
      have been difficult to interpret in light of several conceptual and design flaws.
      Taking a revised methodological approach, including use of newly validated (Study
      1), pathogen-free violations of the divinity code, we found (Study 2) little
      evidence of disgust-related phenomenology (nausea, gagging, loss of appetite) or
      action tendency (desire to move away), but much evidence of anger-linked desire
      to retaliate, as a major component of individuals' projected response to "pure"
      (pathogen-free) violations of the divinity code. Study 3 replicated these results
      using faces in lieu of words as a dependent measure. Concordant findings emerged
      from an archival study (Study 4) examining the aftermath of a real-life sacred
      violation-the burning of Korans by U.S. military personnel. Study 5 further
      corroborated these results using continuous measures based on everyday emotion
      terms and new variants of the divinity-pure scenarios featuring sacrilegious acts
      committed by a theologically irreverent member of one's own group rather than an
      ideologically opposed member of another group. Finally, a supplemental study
      found the anger-dominant attribution pattern to remain intact when the impious
      act being judged was the judge's own. Based on these and related results, we
      posit anger to be the principal emotional response to moral transgressions
      irrespective of the normative content involved.

PMID- 24866520
TI  - The dopamine D4 receptor gene shows a gender-sensitive association with cognitive
      empathy: evidence from two independent samples.
AB  - Increasing evidence points to a role of dopaminergic pathways in modulating
      social behavior. Specifically, a polymorphic region in the third exon of the
      Dopamine D4 receptor (DRD4) has been associated with a host of social behaviors,
      often in an environment-sensitive manner. Empathy is thought to be an important
      motivator of prosocial behaviors and can be seen as multifaceted, combining
      cognitive empathy (CE) and emotional empathy (EE). In the current study, we
      analyzed the association between DRD4 and the 2 aspects of empathy, as well as
      the effect of gender on this association. In Study 1, a large sample of adult
      participants (N = 477) was inventoried for general empathy, CE, and EE and
      genotyped for the DRD4 exon 3 polymorphism. Women scored higher than men on all
      empathy measures and no main effect of genotype was observed. It is important
      that a significant interaction between genotype and gender emerged specifically
      for CE, with women carriers of the 7R-allele scoring higher than noncarriers,
      whereas in men 7R-carriers scored lower than -7R. Notably, these findings were
      replicated in an independently recruited sample (N = 121) in Study 2. The current
      report shows that the DRD4 exon3 polymorphism is associated with CE and the
      direction of the association is gender-sensitive.

PMID- 24866522
TI  - Motivational enhancement of cognitive control depends on depressive symptoms.
AB  - Performance feedback can motivate improvements in executive function (Ravizza,
      Goudreau, Delgado, & Ruiz, 2012). The present study examines whether the
      enhancement of task switching with performance feedback is modulated by the level
      of depressive symptoms. Depressive symptoms have been linked to deficits in
      processing affective information inherent to such feedback (Henriques, Glowacki,
      & Davidson, 1994; Pizzagalli, Jahn, & O'Shea, 2005). Task switching speed was
      assessed when performance feedback about accuracy was present or absent in a
      group of participants with minimal to moderate levels of depression. A
      significant positive correlation was observed between depressive symptoms and
      feedback effects on executive function indicating that those with lower
      depressive symptoms were more likely to show improvements in switching speed when
      performance feedback was present. These results suggest a novel link between
      executive function deficits and depression symptoms; namely, that greater levels
      of depressive symptoms are linked to diminished executive functioning via
      deficits in processing the affective component of performance feedback.

PMID- 24866521
TI  - The amygdala mediates the emotional modulation of threat-elicited skin
      conductance response.
AB  - The ability to respond adaptively to threats in a changing environment is an
      important emotional function. The amygdala is a critical component of the neural
      circuit that mediates many emotion-related processes, and thus likely plays an
      important role in modulating the peripheral emotional response to threat.
      However, prior research has largely focused on the amygdala's response to stimuli
      that signal impending threat, giving less attention to the amygdala's response to
      the threat itself. From a functional perspective, however, it is the response to
      the threat itself that is most biologically relevant. Thus, understanding the
      factors that influence the amygdala's response to threat is critical for a
      complete understanding of adaptive emotional processes. Therefore, we used
      functional MRI to investigate factors (i.e., valence and arousal of co-occurring
      visual stimuli) that influence the amygdala's response to threat (loud white
      noise). We also assessed whether changes in amygdala activity varied with the
      peripheral expression of emotion (indexed via skin conductance response; SCR).
      The results showed that threat-elicited amygdala activation varied with the
      arousal, not valence, of emotional images. More specifically, threat-elicited
      amygdala activation was larger to the threat when presented during high-arousal
      (i.e., negative and positive) versus low-arousal (i.e., neutral) images. Further,
      the threat-elicited amygdala response was positively correlated with threat
      elicited SCR. These findings indicate the amygdala's response to threat is
      modified by the nature (e.g., arousal) of other stimuli in the environment. In
      turn, the amygdala appears to mediate important aspects of the peripheral
      emotional response to threat.

PMID- 24866523
TI  - Life history, code of honor, and emotional responses to inequality in an economic
      game.
AB  - The code of honor, which is characterized by a preoccupation with reputation and
      willingness to take retaliatory action, has been used extensively to explain
      individual and cultural differences in peoples' tendencies to behave
      aggressively. However, research on the relationship between the code of honor and
      emotional responses to social interactions has been limited in scope, focusing
      primarily on anger in response to insults and reputational threats. Here we
      broaden this scope by examining the relationship between code of honor and
      emotional reactions in response to an unfair economic exchange that resulted in
      unequal monetary earnings among 3 laboratory participants. We found that
      endorsement of the code of honor was related to anger and envy in response to
      unfair monetary distributions. Interestingly, code of honor predicted envy above
      and beyond what could be accounted for by anger, but the converse was not the
      case. This suggests that the code of honor influenced perceptions of how subjects
      viewed their own earnings relative to those of others, which consequently was
      responsible for their apparent anger as a result of the economic transaction.
      Furthermore, the unique relationship between code of honor and envy was present
      only for subjects who received unfair treatment and not for subjects who merely
      witnessed unfair treatment. Additionally, we replicated previous findings that
      harsh childhood environmental conditions are associated with endorsement of the
      code of honor, highlighting the potential value of incorporating a life history
      theoretical approach to investigating individual differences in endorsement of
      the code of honor.

PMID- 24866524
TI  - Dynamic facial expressions allow differentiation of displays intended to convey
      positive and hubristic pride.
AB  - Prior research has identified a facial expression for positive pride, but no
      expression for negative pride, hubris. In the present study, professional actors
      created expressions intended to convey hubris. In Study 1 (N = 52), participants
      were shown dynamic expressions and attributed confidence, positive valence, and
      positive personality traits to the positive pride expression, but conceit,
      neutral valence, and negative personality traits to the hubris expression. In
      Study 2 (N = 60), participants were more likely to attribute conceit to a dynamic
      hubris expression than a static one; no such difference was found for positive
      pride.

PMID- 24866525
TI  - The role of instrumental emotion regulation in the emotions-creativity link: how
      worries render individuals with high neuroticism more creative.
AB  - Based on the instrumental account of emotion regulation (Tamir, 2005), the
      current research seeks to offer a novel perspective to the emotions-creativity
      debate by investigating the instrumental value of trait-consistent emotions in
      creativity. We hypothesize that emotions such as worry (vs. happy) are trait
      consistent experiences for individuals higher on trait neuroticism and
      experiencing these emotions can facilitate performance in a creativity task. In 3
      studies, we found support for our hypothesis. First, individuals higher in
      neuroticism had a greater preference for recalling worrisome (vs. happy) events
      in anticipation of performing a creativity task (Study 1). Moreover, when induced
      to recall a worrisome (vs. happy) event, individuals higher in neuroticism came
      up with more creative design (Study 2) and more flexible uses of a brick (Study
      3) when the task was a cognitively demanding one. Further, Study 3 offers
      preliminary support that increased intrinsic task enjoyment and motivation
      mediates the relationship between trait-consistent emotion regulation and
      creative performance. These findings offer a new perspective to the controversy
      concerning the emotions-creativity relationship and further demonstrate the role
      of instrumental emotion regulation in the domain of creative performance.

PMID- 24866527
TI  - Mothers' tone of voice depends on the nature of infants' transgressions.
AB  - Emotional vocal signals are important ways of communicating norms to young
      infants. The second year is a period of increase in various forms of child
      transgressions, but also a period when infants have limited linguistic abilities.
      Two studies investigated the hypothesis that mothers respond with different vocal
      emotional tones to 3 types of child transgressions: moral (harming others),
      prudential (harming oneself), and pragmatic (creating inconvenience, e.g., by
      spilling) transgressions. We used a combination of naturalistic observation
      (Study 1) and experimental manipulation (Study 2) to record, code, and analyze
      maternal vocal responses to child transgressions. Both studies showed that
      mothers were more likely to use intense, angry vocalizations in response to moral
      transgressions, fearful vocalizations in response to prudential transgressions,
      comforting vocalizations in response to pragmatic and prudential transgressions,
      and (in Study 2) playful vocalizations in response to pragmatic transgressions.
      Study 1 showed that this differential use of vocal tone is used systematically in
      everyday life. Study 2 allowed us to standardize the context of the maternal
      intervention and perform additional acoustical analyses. A combination of
      principal component analysis and linear discriminant analysis applied to pitch
      and intensity data provided quantitative measures of the differences in vocal
      responses. These differentiated vocal responses are likely contributors to
      children's acquisition of norms from early in life.

PMID- 24866526
TI  - Emotion regulation moderates the risk associated with the 5-HTT gene and stress
      in children.
AB  - Carrying a short allele in the serotonin transporter polymorphism (5-HTTLPR)
      while experiencing stressful environments is linked to elevated risk for
      depression. What might offset this risky combination of genes and environment? We
      hypothesized that individual-level factors may play a protective role.
      Specifically, we examined whether individuals' ability to decrease their stress
      responses via effective emotion regulation may be an important moderating factor
      and addressed this hypothesis in a socioeconomically diverse sample of 205
      children aged 9-15 years. At-risk children (short-allele carriers in high-stress
      contexts) exhibited more depressive symptoms than other groups. Importantly, at
      risk children who used effective emotion regulation did not exhibit increased
      depressive symptoms. These results have important implications for the basic
      science of understanding risk and resilience: in addition to genes and
      environment, individuals' agentic ability to self-regulate may need to be
      considered as a critical third factor. Given that emotion regulation is
      learnable, these results also have strong public-health implications.

PMID- 24866529
TI  - Daily associations among anger experience and intimate partner aggression within
      aggressive and nonaggressive community couples.
AB  - Anger is an empirically established precipitant to aggressive responding toward
      intimate partners. The current investigation examined the effects of anger, as
      experienced by both partners, as well as gender and previous aggression, on in
      vivo intimate-partner aggression (IPA) using a prospective daily diary
      methodology. Participants (N = 118 couples) individually provided 56 consecutive,
      daily reports of affective experience and partner aggression. Multilevel models
      were estimated using the actor-partner interdependence model (APIM) framework to
      analyze the daily associations between anger and partner-aggression perpetration
      among participating men and women, as moderated by aggression history. Results
      revealed that both actor and partner anger were generally associated with
      subsequently reported daily conflict. Further, increases in daily partner anger
      were associated with corresponding increases in partner aggression among both
      women who reported high levels of anger and men, regardless of their own anger
      experience. Increases in actor anger were associated with increases in daily
      partner aggression only among previously aggressive women. Previously aggressive
      men and women consistently reported greater perpetration than their nonaggressive
      counterparts on days of high levels of actors' anger experiences. Results
      emphasize the importance of both actor and partner factors in partner aggression
      and suggest that female anger may be a stronger predictor of both female-to-male
      and male-to-female partner aggression than male anger, when measured at the daily
      level.

PMID- 24866528
TI  - The negativity bias in affective picture processing depends on top-down and
      bottom-up motivational significance.
AB  - It is widely believed that negative information is psychologically more
      meaningful than positive information, a phenomenon known generally as the
      negativity bias. However, findings concerning the possibility of a negativity
      bias in emotional picture processing have been mixed, with recent studies
      indicating the lack of such a bias in event-related brain potentials (ERPs) when
      pleasant and unpleasant images are equated for motivational relevance. Here, we
      investigated 2 factors that could influence the detection of a negativity bias:
      picture-presentation paradigm and specific picture content. Across 2 studies,
      participants viewed pleasant affiliative, pleasant thrilling, unpleasant
      threatening and neutral images presented in the context of oddball, blocked, and
      random viewing paradigms. Across paradigms, emotional images elicited larger
      responses in the late positive potential (LPP) than did neutral images. A
      negativity bias was detected in the oddball paradigm and when thrilling, rather
      than affiliative, pleasant stimuli were used. Findings are discussed in terms of
      factors known to influence LPP amplitude and their relevance to differential
      effects across picture-viewing paradigms.

PMID- 24866530
TI  - Pancultural nostalgia: prototypical conceptions across cultures.
AB  - Nostalgia is a frequently experienced complex emotion, understood by laypersons
      in the United Kingdom and United States of America to (a) refer prototypically to
      fond, self-relevant, social memories and (b) be more pleasant (e.g., happy, warm)
      than unpleasant (e.g., sad, regretful). This research examined whether people
      across cultures conceive of nostalgia in the same way. Students in 18 countries
      across 5 continents (N = 1,704) rated the prototypicality of 35 features of
      nostalgia. The samples showed high levels of agreement on the rank-order of
      features. In all countries, participants rated previously identified central (vs.
      peripheral) features as more prototypical of nostalgia, and showed greater
      interindividual agreement regarding central (vs. peripheral) features. Cluster
      analyses revealed subtle variation among groups of countries with respect to the
      strength of these pancultural patterns. All except African countries manifested
      the same factor structure of nostalgia features. Additional exemplars generated
      by participants in an open-ended format did not entail elaboration of the
      existing set of 35 features. Findings identified key points of cross-cultural
      agreement regarding conceptions of nostalgia, supporting the notion that
      nostalgia is a pancultural emotion.

PMID- 24866531
TI  - Integration of negative emotional experience versus suppression: addressing the
      question of adaptive functioning.
AB  - Integrative emotion regulation is defined as the ability to experience negative
      emotions, explore their sources, and use this exploration for volitional
      regulation of behavior. Empirical research on integrative regulation is quite
      scarce and relies mainly on self-reports. The present research comprised 2
      studies exploring the behavioral, emotional, and cognitive consequences of
      integrative emotion regulation and suppression of emotion, in relation to a fear
      eliciting film. Study 1 examined associations between emotion regulation types
      (self-reported) and defensive versus nondefensive emotional processing (coded
      from postfilm open-ended written texts) in 80 Israeli college students. In Study
      2, we manipulated the emotion regulation types by assigning 120 Israeli college
      students to integrative, suppressive, and control (neutral) conditions and
      exposing them twice to the same fear-eliciting film, 72 hr apart. We hypothesized
      that in the second exposure to the film, participants who were instructed to
      practice integrative regulation would benefit more than participants in the other
      2 groups in terms of lower arousal level related to an experience of fear
      (measured by skin conductance, physical observation, and self-report) and better
      cognitive capacity (on a recall test). In general, the results supported our
      hypotheses. In comparison to suppression, integrative regulation was associated
      with less defensive written expression in the first study and with lower arousal
      and better cognitive recall in the second study. Hence, current outcomes provide
      some support for the assumption that taking interest in and accepting one's
      negative emotions is linked with less defensive processing of negative
      experiences and with better functioning.

PMID- 24866532
TI  - The inhibition of proactive interference among adults with Internet gaming
      disorder.
AB  - INTRODUCTION: Cognitive control plays a pivotal role in the mechanism of
      addictive behavior. The aim of the study was to evaluate the deficit in
      inhibition of proactive interference of Internet gaming disorder (IGD) using a
      directed forgetting task among young adults. METHODS: A total of 64 participants
      with IGD and 69 controls were recruited on a university campus. They completed
      the directed forgetting task for online gaming words and neutral words. RESULTS:
      The results demonstrated that the IGD group had a poorer performance on the
      directed forgetting task, and this represented a deficit in inhibition of
      proactive interference. They also had a higher tendency to remember online gaming
      words rather than neutral words in comparison with the control group. This
      demonstrated memory bias toward online gaming words. DISCUSSION: These results
      suggested that more attention should be paid to deficits in inhibition of
      proactive interference and memory bias toward gaming content when treating
      subjects with IGD. Furthermore, it is essential and practical to prevent exposure
      to online gaming-related cues when endeavoring to control online gaming behavior.

PMID- 24866533
TI  - Getting at the root of the mountain pine beetle's rapid habitat expansion and
      forest devastation.

PMID- 24866535
TI  - On the formation of (anionic) excited helium dimers in helium droplets.
AB  - Metastable atomic and molecular helium anions exhibiting high-spin quartet
      configurations can be produced in helium droplets via electron impact. Their
      lifetimes allow detection in mass spectrometric experiments. Formation of atomic
      helium anions comprises collision-induced excitation of ground state helium and
      concomitant electron capture. Yet the formation of molecular helium anions in
      helium droplets has been an unresolved issue. In this work, we explore the
      interaction of excited helium atoms exhibiting high-spin triplet configurations
      with ground state helium using the equation-of-motion coupled-cluster method.
      Transition barriers in the energetically lowest He*-He and He*(-)-He interaction
      potentials prevent molecule formation at the extremely low temperatures present
      in helium droplets. In contrast, some excited states allow a barrier-free
      formation of molecular helium (anions). Moreover, we show that the necessary
      excitation energies pinpoint (higher) resonances in recently recorded mass
      spectra and emend the assignment of those resonances that have previously been
      assigned to electron-impact ionization of ground state helium necessitating
      subsequent double-electron capture. Embedding molecules or molecular clusters in
      helium droplets is a predestined experimental technique for the study of
      phenomena at very low temperatures. Profound knowledge about active processes in
      the helium environment is required for a proper assessment of experimental data. 

PMID- 24866534
TI  - Erasing errors due to alignment ambiguity when estimating positive selection.
AB  - Current estimates of diversifying positive selection rely on first having an
      accurate multiple sequence alignment. Simulation studies have shown that under
      biologically plausible conditions, relying on a single estimate of the alignment
      from commonly used alignment software can lead to unacceptably high false
      positive rates in detecting diversifying positive selection. We present a novel
      statistical method that eliminates excess false positives resulting from
      alignment error by jointly estimating the degree of positive selection and the
      alignment under an evolutionary model. Our model treats both substitutions and
      insertions/deletions as sequence changes on a tree and allows site heterogeneity
      in the substitution process. We conduct inference starting from unaligned
      sequence data by integrating over all alignments. This approach naturally
      accounts for ambiguous alignments without requiring ambiguously aligned sites to
      be identified and removed prior to analysis. We take a Bayesian approach and
      conduct inference using Markov chain Monte Carlo to integrate over all alignments
      on a fixed evolutionary tree topology. We introduce a Bayesian version of the
      branch-site test and assess the evidence for positive selection using Bayes
      factors. We compare two models of differing dimensionality using a simple
      alternative to reversible-jump methods. We also describe a more accurate method
      of estimating the Bayes factor using Rao-Blackwellization. We then show using
      simulated data that jointly estimating the alignment and the presence of positive
      selection solves the problem with excessive false positives from erroneous
      alignments and has nearly the same power to detect positive selection as when the
      true alignment is known. We also show that samples taken from the posterior
      alignment distribution using the software BAli-Phy have substantially lower
      alignment error compared with MUSCLE, MAFFT, PRANK, and FSA alignments. 

PMID- 24866537
TI  - Non-metastatic castration-resistant prostate cancer (CPRCM0), an old scenario
      with renewed clinical interest.

PMID- 24866536
TI  - Combination of HDAC inhibitor MS-275 and IL-2 increased anti-tumor effect in a
      melanoma model via activated cytotoxic T cells.
AB  - BACKGROUND: Histone deacetylase (HDAC) inhibitors are immunomodulatory, and
      demonstrate antitumor activity in various tumor models including malignant
      melanoma. OBJECTIVE: The present study examines the effectiveness of IL-2 and
      HDAC inhibitor MS-275-combination therapy in a murine melanoma model. METHODS:
      B16F10 cells were implanted subcutaneously in C57BL/6 mice which were randomly
      divided into four groups and treated with either IL-2 by subcutaneous injection,
      MS-275 by oral gavage (5 days/week, daily for 2 weeks), or a combination of the
      two agents. RESULTS: MS-275 treatment showed a dose-dependent inhibitory effect
      on B16 cells in a colonogenic assay. Flow cytometry analysis indicated that MS
      275 induced G1 arrest but not apoptosis in vitro, but IL-2 failed to inhibit cell
      proliferation. The combination of MS-275 and IL-2 had a statistically significant
      additive inhibitory effect on melanoma tumor weight and volume in vivo.
      Significantly higher survival was evident in the combination group compared with
      the control or single-agent groups. The combination therapy produced a greater
      ratio of CD8(+) CD69(+) T cells in lymph nodes than was seen in the MS-275
      treatment and no-treatment groups among tumoriferous mice. Splenocytes from mice
      treated with MS-275 and the combination therapy demonstrated greater lysis of
      melanoma cells in vitro than splenocytes from mice treated with IL-2 or those
      without treatment. A significant antitumor effect from IL-2 and MS-275
      combination therapy in vivo was seen in the increased number of activated CD8(+)
      T cells. CONCLUSIONS: These data provide a convincing rationale for considering
      the role of epigenetics in future treatments for malignant melanoma.

PMID- 24866538
TI  - Observation stays in administrative claims databases: underestimation of
      hospitalized cases.
AB  - PURPOSE: Recent policy changes in the USA have led to an increasing number of
      patients being placed into observation units rather than admitted directly to the
      hospital. Studies of administrative data that use inpatient diagnosis codes to
      identify cohorts, outcomes, or covariates may be affected by this change in
      practice. To understand the potential impact of observation stays on research
      using administrative healthcare data, we examine the trends of observation stays,
      short (<=2 days) inpatient admissions, and all inpatient admissions. METHODS: We
      examined a large administrative claims database of commercially insured
      individuals in the USA between 2002 and 2011. Observation stays were defined on
      the basis of the procedure codes reimbursable by Medicare or commercial insurers.
      We report monthly rates of observation stays and short inpatient admissions
      overall and by patient demographics. RESULTS: We identified 5 355 752 observation
      stays from 2002 to 2011. Over the course of study, the rate of observation stays
      increased, whereas the rate of short inpatient stays declined. The most common
      reason for observation stays was nonspecific chest pain, also the third most
      common reason for short inpatient stays. The increasing trend of observation
      stays related to circulatory diseases mirrors the decreasing trend of short
      inpatient stays. CONCLUSIONS: The use of observation stays has increased in
      patients with commercial insurance. Failure to account for observation stays may
      lead to an under-ascertainment of hospitalizations in contemporary administrative
      healthcare data from the USA.

PMID- 24866540
TI  - Lessons I have learnt about the cornea: comment.

PMID- 24866541
TI  - Pitfalls in communication that lead to nonbeneficial emergency surgery in elderly
      patients with serious illness: description of the problem and elements of a
      solution.
AB  - OBJECTIVE: To provide a description of communication breakdowns and to identify
      interventions to improve surgical decision making for elderly patients with
      serious illness and acute, life-threatening surgical conditions. BACKGROUND:
      Communication between surgeons, patients, and surrogates about goals of treatment
      plays an important and understudied role in determining the surgical
      interventions elderly patients with serious illness receive. Communication
      breakdowns may lead to nonbeneficial procedures in acute events near the end of
      life. METHODS: We review the available literature on factors that lead to
      communication challenges and nonbeneficial surgery at the end of life. We use
      this review to identify solutions for navigating surgical decision making for
      seriously ill elderly patients with acute surgical conditions. RESULTS: Surgeon,
      patient, surrogate, and systemic factors-including time constraints, inadequate
      provider communication skills and training, uncertainty about prognosis, patient
      and surrogate anxiety and fear of inaction, and limitations in advance care
      planning-contribute to communication challenges and nonbeneficial surgery at the
      end of life. Surgeons could accomplish more effective communication with
      seriously ill elderly patients if they had a structured, standardized approach to
      exploring patients' preferences and to integrating those preferences into
      surgical decisions in the acute setting. CONCLUSIONS: Improved communication
      among surgeons, patients, and surrogates is necessary to ensure that patients
      receive the care that they want and to avoid nonbeneficial treatment. Further
      research is needed to learn how to best structure these conversations in the
      emergency surgical setting.

PMID- 24866539
TI  - Differential requirement for P2X7R function in IL-17 dependent vs. IL-17
      independent cellular immune responses.
AB  - IL17-dependent autoimmunity to collagen type V (Col V) has been associated with
      lung transplant obliterative bronchiolitis. Unlike the T helper 1 (Th1)-dependent
      immune responses to Tetanus Toxoid (TT), the Th17 response to Col V in lung
      transplant patients and its Th1/17 variant observed in coronary artery disease
      patients requires IL-1beta, tumor necrosis factor alpha and CD14(+) cells. Given
      the involvement of the P2X7 receptor (P2X7R) in monocyte IL-1beta responses, we
      investigated its role in Th17-, Th1/17- and Th1-mediated proinflammatory
      responses. Transfer of antigen-pulsed peripheral blood mononucleated cells
      (PBMCs) from Col V-reactive patients into SCID mouse footpads along with P2X7R
      antagonists revealed a selective inhibition of Col V-, but not TT-specific
      swelling responses. P2X7R inhibitors blocked IL-1beta induction from monocytes,
      including both Col V-alpha1 peptide-induced (T-dependent), as well as native Col
      V-induced (T-independent) responses. Significantly higher P2X7R expression was
      found on CXCR3(neg) CCR4(+)/6(+) CD4(+) [Th17] versus CXCR3(+)CCR4/6(neg) CD4(+)
      [Th1] subsets in PBMCs, suggesting that the paradigm of selective dependence on
      P2X7R might extend beyond Col V autoimmunity. Indeed, P2X7R inhibitors suppressed
      not only anti-Col V, but also Th1/17-mediated alloimmunity, in a heart transplant
      patient without affecting anti-viral Epstein-Barr virus responses. These results
      suggest that agents targeting the P2X7R might effectively treat Th17-related
      transplant pathologies, while maintaining Th1-immunity to infection.

PMID- 24866542
TI  - Use of liver magnetic resonance imaging after standard staging abdominopelvic
      computed tomography to evaluate newly diagnosed colorectal cancer patients.
AB  - OBJECTIVE: To investigate the impact of liver magnetic resonance imaging (MRI) in
      staging evaluation of newly diagnosed colorectal cancer patients. BACKGROUND: No
      clear guidelines regarding how to use liver MRI in evaluating newly diagnosed
      colorectal cancer. METHODS: We included 863 adults who had newly diagnosed
      colorectal cancer without concomitant malignancies and received portal-phase
      contrast-enhanced abdominopelvic computed tomography (CT). Patients who had
      diminutive indeterminate hypoattenuating ["too-small-to-characterize" (TSTC)]
      hepatic lesions without other suspicious/indeterminate findings (TSTC-liver-on
      CT), metastasis-negative hepatic findings (negative-liver-on-CT), and hepatic
      lesions suspicious or indeterminate for metastasis excluding TSTC lesions as seen
      on CT were identified. Per-patient rate of hepatic metastasis unsuspected by CT
      and the diagnostic yield of liver MRI for such lesions were assessed. RESULTS:
      There were 261 TSTC-liver-on-CT patients, 464 negative-liver-on-CT patients, and
      138 patients with suspicious hepatic findings on CT. Among TSTC-liver-on-CT
      patients, the rate of hepatic metastasis was 2.2% (5/230, excluding patients
      without follow-up) and the yield of liver MRI was 3% (3/96). Negative-liver-on-CT
      patients gave the MRI yield of 0% (0/94). Among negative-liver-on-CT patients,
      the rate of hepatic metastasis discovered within 6 months of curative surgery was
      1.1% (4/350, excluding patients without follow-up) when the liver was cleared by
      negative CT alone and 2% (2/88, excluding patients without follow-up) when
      cleared also by negative MRI (P = 0.347). Among the patients who had suspicious
      hepatic findings on CT, the MRI yield was 25% (19/77). CONCLUSIONS: The
      diagnostic yield of liver MRI for hepatic metastasis was very low in newly
      diagnosed colorectal cancer patients who showed TSTC hepatic lesions or
      metastasis-negative hepatic findings on CT. Staging liver MRI is likely
      unnecessary for them.

PMID- 24866543
TI  - Simplifying the ALPPS procedure by the anterior approach.

PMID- 24866544
TI  - Computerized Tomography-based Diagnosis of Sarcopenia?

PMID- 24866545
TI  - Hey, I just did a new operation!: Introducing innovative procedures and devices
      within an academic health center.

PMID- 24866546
TI  - The evolution and future of scientific communication: American Surgical
      Association presidential address.

PMID- 24866547
TI  - Focusing on the new reality in trauma care.

PMID- 24866552
TI  - Four-dimensional visualization of rising microbubbles.
AB  - Four-dimensional imaging, which indicates imaging in three spatial dimensions as
      a function of time, provides useful evidence to investigate the interactions of
      rising bubbles. However, this has been largely unexplored for microbubbles,
      mostly due to problems associated with strong light scattering and shallow depth
      of field in optical imaging. Here, tracking x-ray microtomography is used to
      visualize rising microbubbles in four dimensions. Bubbles are tracked by moving
      the cell to account for their rise velocity. The sizes, shapes, time-dependent
      positions, and velocities of individual rising microbubbles are clearly
      identified, despite substantial overlaps between bubbles in the field of view.
      Our tracking x-ray microtomography affords opportunities for understanding bubble
      bubble (or particle) interactions at microscales - important in various fields
      such as microfluidics, biomechanics, and floatation. 

PMID- 24866554
TI  - MicroRNA-137 regulates a glucocorticoid receptor-dependent signalling network:
      implications for the etiology of schizophrenia.
AB  - BACKGROUND: Schizophrenia is a highly heritable neurodevelopmental disorder. A
      genetic variant of microRNA-137 (miR-137) has yielded significant genome-wide
      association with schizophrenia, suggesting that this miRNA plays a key role in
      its etiology. Therefore, a molecular network of interacting miR-137 targets may
      provide insights into the biological processes underlying schizophrenia. METHODS:
      We first used bioinformatics tools to obtain and analyze predicted human and
      mouse miR-137 targets. We then determined miR-137 levels in rat barrel cortex
      after environmental enrichment (EE), a neuronal plasticity model that induces
      upregulation of several predicted miR-137 targets. Subsequently, expression
      changes of these predicted targets were examined through loss of miR-137 function
      experiments in rat cortical neurons. Finally, we conducted bioinformatics and
      literature analyses to examine the targets that were upregulated upon miR-137
      downregulation. RESULTS: Predicted human and mouse miR-137 targets were enriched
      in neuronal processes, such as axon guidance, neuritogenesis and
      neurotransmission. The miR-137 levels were significantly downregulated after EE,
      and we identified 5 novel miR-137 targets through loss of miR-137 function
      experiments. These targets fit into a glucocorticoid receptor-dependent
      signalling network that also includes 3 known miR-137 targets with genome-wide
      significant association with schizophrenia. LIMITATIONS: The bioinformatics
      analyses involved predicted human and mouse miR-137 targets owing to lack of
      information on predicted rat miR-137 targets, whereas follow-up experiments were
      performed with rats. Furthermore, indirect effects in the loss of miR-137
      function experiments cannot be excluded. CONCLUSION: We have identified a miR-137
      regulated protein network that contributes to our understanding of the molecular
      basis of schizophrenia and provides clues for future research into
      psychopharmacological treatments for schizophrenia.

PMID- 24866557
TI  - Director/barycentric rotation in cholesteric droplets under temperature gradient.
AB  - When a chiral liquid crystal is given a transport current, a unidirectional
      molecular motion is known to take place, which is called the Lehmann effect. In
      this paper, we study the mysterious heat-current-driven Lehmann effect using two
      types of hemispherical cholesteric droplets using polarizing, reflecting,
      confocal and fluorescent microscopies. Both the droplets, coexisting with the
      isotropic phase and contacting on a glass substrate, are characterized by the
      concavo-convex modulated surface and the inside orientational helix. Further, the
      only difference between them is the helical axis direction; i.e., one is
      perpendicular and the other is parallel to the substrate. Under the temperature
      gradient perpendicular to the substrate, the droplet whose helical axis is
      parallel to the heat current exhibited pure director rotation, while that with
      the axis perpendicular to the current rotated independently as a rigid body. In
      the two droplets, the rotational conversion efficiency from the temperature
      gradient into the angular velocity showed very different dependences on the
      chirality strength and on the droplets' size, suggesting that the rotations of
      the two droplets may be driven by independent torques with different origins.
      This is the first observation that the cholesteric droplets under the temperature
      gradient exhibit the two rotational modes, the pure director rotation and the
      molecular barycentric motion, which can be switched to each other by changing the
      heat-current direction parallel and perpendicular to the helical axis. 

PMID- 24866556
TI  - Executive function moderates the relation between coping and depressive symptoms.
AB  - BACKGROUND AND OBJECTIVES: Identifying risk factors early in the course of
      depression has important implications for prevention, given that the likelihood
      of recurrence increases with each successive episode. DESIGN: This study examined
      relations among coping, executive functioning, and depressive symptom
      trajectories in a sample of remitted-depressed (n = 32) and never-depressed (ND;
      n = 36) young adults (aged 18-31). METHODS: Participants completed a clinical
      interview, a measure of coping, and tasks assessing two components of executive
      function - inhibition and cognitive flexibility. Participants were reassessed
      regarding the timing and severity of depressive symptoms that had occurred during
      the interval period (mean = 35.16 weeks, SD = 9.03). RESULTS: Among ND
      individuals, less primary control coping (e.g., problem-solving) and greater
      disengagement coping (e.g., avoidance) predicted increases in depressive
      symptoms. Greater secondary control coping (e.g., acceptance) predicted decreases
      in depressive symptoms and was unrelated to depression history. Higher inhibition
      scores predicted less increase in depressive symptoms for individuals reporting
      less primary control coping or more disengagement coping. Higher cognitive
      flexibility scores predicted less increase in depressive symptoms among
      individuals reporting less secondary control coping. CONCLUSIONS: Interventions
      aiming to enhance either coping strategies or executive functions may reduce risk
      of depression recurrence.

PMID- 24866555
TI  - Terpenes and lipids of the endocannabinoid and transient-receptor-potential
      channel biosignaling systems.
AB  - Endocananbnoid-system G-protein coupled receptors (GPCRs) and transient receptor
      potential (TRP) cation channels are critical components of cellular biosignaling
      networks. These plasma-membrane proteins are pleiotropic in their ability to
      interact with and engage structurally diverse ligands. The endocannabinoid and
      TRP signaling systems overlap in their recognition properties with respect to
      select naturally occurring plant-derived ligands that belong to the terpene and
      lipid chemical classes, the overlap establishing a physiological connectivity
      between these two ubiquitous cell-signaling systems. Identification and
      pharmacological profiling of phytochemicals engaged by cannabinoid GPCRs and/or
      TRP channels has inspired the synthesis of novel designer ligands that interact
      with cannabinoid receptors and/or TRP channels as xenobiotics. Functional
      interplay between the endocannabinoid and TRP-channel signaling systems is
      responsible for the antinocifensive action of some synthetic cananbinoids
      (WIN55,212-2 and AM1241), vasorelaxation by the endocannabinoid N
      arachidonylethanolamide (anandamide), and the pain-relief afforded by the
      synthetic anandamide analogue N-arachidonoylaminophenol (AM404), the active
      metabolite of the widely used nonprescription analgesic and antipyretic
      acetaminophen (paracetamol). The biological actions of some plant-derived
      cannabinoid-receptor (e.g., Delta(9)-tetrahydrocannabinol) or TRP-channel (e.g,,
      menthol) ligands either carry abuse potential themselves or promote the use of
      other addictive substances, suggesting the therapeutic potential for modulating
      these signaling systems for abuse-related disorders. The pleiotropic nature of
      and therapeutically relevant interactions between cananbinergic and TRP-channel
      signaling suggest the possibility of dual-acting ligands as drugs.

PMID- 24866559
TI  - Phosphorous and sulfur nutrition modulate antioxidant defenses in Myracrodruom
      urundeuva plants exposed to arsenic.
AB  - We investigated if plant nutrition and antioxidant system activation are
      correlated features of arsenic (As)-tolerance in Myracrodruom urundeuva. Plants
      were grown for 120 days in substrates with 0, 10, 50 and 100mg Askg(-1) and its
      As-tolerance was demonstrated. As-concentrations greater than 10mgkg(-1)
      decreased plant growth and photosynthesis but did not induce plant death. Plants
      coupled alterations in stomatal conductance and transpiration to avoid As
      deleterious effects to the photosynthetic apparatus. As-toxicity in M. urundeuva
      was due to lipid peroxidation induced by hydrogen peroxide accumulation.
      Ascorbate peroxidase (APX) and gluthatione peroxidase (GPX) had central roles in
      hydrogen peroxide (H2O2) scavenging in leaves, and their activities were linked
      to changes in redox potentials (ascorbate and glutathione pools). APX and GPX
      inactivation/degeneration led to H2O2 accumulation and related lipid
      peroxidation. Increased phosphorus (P) and sulfur (S) concentrations in leaves
      were related to increased APX and GPX activities by stimulating increases in
      glutathione biosynthesis. We concluded that P and S nutrition were directly
      linked to As-tolerance in M. urundeuva plants by increasing antioxidant system
      activities. 

PMID- 24866558
TI  - Molecular and serological study of rickettsial infection in humans, and in wild
      and farm animals, in the province of Burgos, Spain.
AB  - Limited information is available on the presence of rickettsial infection in
      humans and animal reservoirs in Spain. Exposure to spotted fever group rickettsia
      in healthy humans and in farm and wild animals in the Province of Burgos, Spain,
      was examined by serological methods. Rickettsial DNA was also sought by PCR in
      animal samples. Of 102 human serum samples examined by indirect
      immunofluorescence assays (IFA), 5.88% were positive for antibodies against
      Rickettsia conorii (titers 1/128-1/512). Significant differences were detected in
      human seroprevalence with respect to age. In further IFAs, 102 out of 375 (27.2%)
      serum samples from the wild animals reacted with R. conorii antigens (titers 1/64
      1/1024); 32 out of 281 (11.38%) samples from farm animals were also positive for
      R. conorii (titers 1/64-1/2048). The prevalence detected among total wild animals
      was significantly higher than among total farm animals. No rickettsial DNA was
      found by PCR in any farm or wild animal sample.

PMID- 24866560
TI  - Studies on electrochemical oxidation of estrogenic disrupting compound bisphenol
      AF and its interaction with human serum albumin.
AB  - Bisphenol AF (BPAF) is an environmental pollutant to disrupt endocrine system or
      cause cancer, thus the detection of trace BPAF is very important. In this study,
      a simple and highly sensitive electroanalytical method for the determination of
      BPAF was developed. In pH 6.0 phosphate buffer solutions, carboxyl functionalized
      multi-walled carbon nanotubes (MWCNT-COOH) modified glassy carbon electrode
      exhibits an enhanced effectiveness for the oxidation of BPAF. This electrode
      exhibited two linear relationships with BPAF concentration range of 0.02MUmolL(
      1) to 8.0MUmolL(-1) and a detection limit of 0.0077MUmolL(-1) (S/N=3). The
      proposed method was successfully applied to determine BPAF in real samples and
      the results were satisfactory. The MWCNT-COOH/GCE electrode showed good
      reproducibility, stability and anti-interference. The electrochemistry and
      spectroscopy methods are also described for the evaluation of BPAF-HSA
      interaction. In the presence of HSA, the peak currents of BPAF decreased linearly
      due to the formation of a super-molecular complex. The binding constant between
      BPAF and HSA, obtained by differential pulse voltammetry (DPV), was consistent
      with the fluorescence analysis. The molecular modeling studies were carried out
      to clearly describe the interaction between BPAF and HSA. 

PMID- 24866561
TI  - Biosorption and biodegradation of triphenyltin by Stenotrophomonas maltophilia
      and their influence on cellular metabolism.
AB  - Triphenyltin (TPT), an endocrine disruptor, is polluting the global environment
      through its worldwide use. However, information concerning the mechanisms of TPT
      biodegradation and cellular metabolism is severely limited. Therefore, these
      processes were elucidated through experiments involving TPT biosorption and
      degradation, intracellular metabolite analysis, nutrient use, ion and
      monosaccharide release, cellular membrane permeability and protein concentration
      quantification. The results verified that TPT was initially adsorbed by the cell
      surface of Stenotrophomonas maltophilia and was subsequently transported and
      degraded intracellularly with diphenyltin and monophenyltin production. Cl(-),
      Na(+), arabinose and glucose release, membrane permeability and the extracellular
      protein concentration increased during TPT treatment, whereas K(+) and PO4(3-)
      utilization and intracellular protein concentration declined. The biosorption,
      degradation and removal efficiencies of TPT at 0.5mgL(-1) by 0.3gL(-1) viable
      cells at 10 d were 3.8, 77.8 and 86.2%, respectively, and the adsorption
      efficiency by inactivated cells was 72.6%. 

PMID- 24866562
TI  - Association of sympathovagal imbalance with cardiovascular risks in patients with
      polycystic ovary syndrome.
AB  - Polycystic ovary syndrome (PCOS) is associated with cardiovascular risks like
      obesity, insulin resistance, dyslipidemia that can lead to sympathovagal
      imbalance (SVI). The study was designed to assess the cardiovascular risk in PCOS
      and link of metabolic derangements to SVI. Thirty-five newly diagnosed PCOS
      patients and 32 age-matched controls were recruited. Waist-hip ratio, body mass
      index (BMI), basal cardiovascular parameters such as basal heart rate (BHR),
      systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial
      pressure (MAP) and rate pressure product (RPP) were recorded. Autonomic functions
      were assessed using short-term heart rate variability (HRV) analysis, heart rate
      and blood pressure response to standing (30:15 ratio), deep breathing (E:I ratio)
      and isometric handgrip (DeltaDBPihg). Fasting plasma glucose, insulin, lipid
      profile and testosterone were assayed. Insulin resistance (HOMA-IR) and lipid
      risk factors were calculated. The cases had increased BHR, BMI, SBP, DBP, MAP and
      RPP. The ratio of low-frequency to high-frequency (LF-HF) of HRV, the marker of
      SVI was significantly increased in cases. 30:15 ratio and DeltaDBPihg were
      increased and E:I ratio was decreased in the cases. HOMA-IR, lipid risk factors
      and testosterone were significantly elevated in cases. There was a significant
      correlation of LF-HF with BMI, BHR, RPP, insulin resistance and lipid risk
      factors. On regression analysis, insulin resistance and lipid risk factors had
      independent association with LF-HF. PCOS patients have SVI, decreased HRV and
      increased RPP and the potential cardiovascular risks. The insulin resistance and
      dyslipidemia contribute to SVI and cardiovascular risks in PCOS patients.

PMID- 24866563
TI  - Continuous separation of protein loaded nanoparticles by simulated moving bed
      chromatography.
AB  - For scale up and efficient production of protein loaded nanoparticles continuous
      separation by size exclusion chromatography in simulated moving bed (SMB) mode
      helps do reduce unbound protein concentration and increase yields for perfectly
      covered particles. Silica nanoparticles were loaded with an excess of beta casein
      or bovine serum albumin (BSA) and the loaded particles purified by size exclusion
      chromatography using Sephacryl300 as stationary phase in a four zone SMB. We
      determined our working points for the SMB from batch separations and the triangle
      theory described by Mazzotti et al. with an SMB setup of one Sephacryl300 26/70mm
      column per zone with switch times of 5min for BSA and 7min for beta casein. In
      the case of BSA the Raffinate contained loaded nanoparticles of 63% purity with
      98% recovery and the extract was essentially particle free (95% purity). We
      showed that the low purity of the Raffinate was only due to BSA multimers present
      in the used protein solution. In the case of beta casein where no multimers are
      present we achieved 89% purity and 90% recovery of loaded nanoparticles in the
      Raffinate and an extract free of particles (92% purity). Using a tangential flow
      filtration unit with 5kDa cutoff membrane we proved that the extract can be
      concentrated for recycling of protein and buffer. The calculated space-time-yield
      for loaded nanoparticles was 0.25g of loaded nanoparticles per hour and liter of
      used resin. This proves that the presented process is suitable for large scale
      production for industrial purposes. 

PMID- 24866564
TI  - Improved micromachined column design and fluidic interconnects for programmed
      high-temperature gas chromatography separations.
AB  - This work focuses on the development and experimental evaluation of micromachined
      chromatographic columns for use in a commercial gas chromatography (GC) system. A
      vespel/graphite ferrule based compression sealing technique is presented using
      which leak-proof fluidic interconnection between the inlet tubing and the
      microchannel was achieved. This sealing technique enabled separation at
      temperatures up to 350 degrees C on a MUGC column. This paper reports the first
      high-temperature separations in microfabricated chromatographic columns at these
      temperatures. A 2m microfabricated column using a double Archimedean spiral
      design with a square cross-section of 100MUm*100MUm has been developed using
      silicon microfabrication techniques. The microfabricated column was benchmarked
      against a 2m 100MUm diameter commercial column and the performance between the
      two columns was evaluated in tests performed under identical conditions. High
      temperature separations of simulated distillation (ASTM2887) and polycyclic
      aromatic hydrocarbons (EPA8310) were performed using the MUGC column in
      temperature programmed mode. The demonstrated MUGC column along with the high
      temperature fixture offers one more solution toward potentially realizing a
      portable MUGC device for the detection of semi-volatile environmental pollutants
      and explosives without the thermal limitations reported to date with MUGC columns
      using epoxy based interconnect technology. 

PMID- 24866565
TI  - A rapid and simple method for simultaneous determination of triphenylmethane dye
      residues in rainbow trouts by liquid chromatography-tandem mass spectrometry.
AB  - A rapid and simple LC-MS/MS method was developed and optimized for screening and
      confirmation of triphenylmethane dyes including malachite green (MG),
      leucomalachite green (LMG), crystal violet (CV), leucocrystal violet (LCV) and
      brilliant green (BG) in fish muscle with skin. Leucocrystal violet D6 (LCV-D6)
      and leucomalachite green-D5 (LMG D5) was used as internal standards. Sample
      preparation is a simple procedure based on solid-liquid extraction with
      acetonitrile containing 1% acetic acid, followed by centrifugation and
      evaporation of the supernatant. The residue was dissolved in acetonitrile with
      0.1% acetic acid and centrifuged prior to LC-MS/MS analysis. Chromatographic
      separation of analytes was performed on an Inertsil ODS-4 C18 column with
      ammonium acetate buffer in acetonitrile gradient. The mass detection was
      performed on a triple-quadrupole tandem mass spectrometer by multiple reaction
      monitoring (MRM) mode via electrospray ionization (ESI+). The developed method
      was validated according to the criteria set in Commission Decision 2002/657/EC.
      The decision limit (CCalpha) was 0.43, 0.24, 0.33, 0.28 and 0.17MUgkg(-1) for MG,
      LMG, CV, LCV and BG respectively. The detection capability (CCbeta) values
      obtained were 0.56, 0.31, 0.43, 0.37 and 0.22MUgkg(-1), respectively. The
      precision of the method, expressed as relative standard deviation (RSD) values
      for the within-day and inter-day laboratory reproducibility, for MG, LMG, CV, LCV
      and BG at the four levels of fortification (0.3, 0.5, 1, and 2MUgkg(-1)), was
      less than 16 and 19% respectively. Accuracy of the method was confirmed by
      successful participation of a proficiency test organized by FAPAS. The method has
      been used for the analysis of 208 fish samples of which seven samples were found
      to be non-compliant containing low residues of LMG and LCV. 

PMID- 24866553
TI  - Convergent pharmacological mechanisms in impulsivity and addiction: insights from
      rodent models.
AB  - Research over the last two decades has widely demonstrated that impulsivity, in
      its various forms, is antecedent to the development of drug addiction and an
      important behavioural trait underlying the inability of addicts to refrain from
      continued drug use. Impulsivity describes a variety of rapidly and prematurely
      expressed behaviours that span several domains from impaired response inhibition
      to an intolerance of delayed rewards, and is a core symptom of attention deficit
      hyperactivity disorder (ADHD) and other brain disorders. Various theories have
      been advanced to explain how impulsivity interacts with addiction both causally
      and as a consequence of chronic drug abuse; these acknowledge the strong overlaps
      in neural circuitry and mechanisms between impulsivity and addiction and the
      seemingly paradoxical treatment of ADHD with stimulant drugs with high abuse
      potential. Recent years have witnessed unprecedented progress in the elucidation
      of pharmacological mechanisms underpinning impulsivity. Collectively, this work
      has significantly improved the prospect for new therapies in ADHD as well as our
      understanding of the neural mechanisms underlying the shift from recreational
      drug use to addiction. In this review, we consider the extent to which
      pharmacological interventions that target impulsive behaviour are also effective
      in animal models of addiction. We highlight several promising examples of
      convergence based on empirical findings in rodent-based studies.

PMID- 24866566
TI  - CT coronary angiography in low- to intermediate-risk patients: less radiation,
      less invasive angiography, and less revascularisation.
AB  - OBJECTIVES: We investigated whether any change in the use of invasive coronary
      angiography and coronary revascularisation after CT coronary angiography in
      patients with a low to intermediate pre-test probability of coronary artery
      disease could be explained from alterations in patient characteristics. DESIGN: A
      cohort study based on data samples from the Western Denmark Heart Registry.
      Follow-up ended on 11 March 2014. RESULTS: A total of 3541 persons were examined
      during the period of January 2010-December 2013. The median radiation dose was
      reduced from 4.2 to 2.2 mSv (p < 0.001) due to improved technology. The immediate
      referral rate for subsequent myocardial perfusion scans was increased from 2.8%
      to 10.0% (p < 0.001), while the immediate referral rate for invasive coronary
      angiography decreased from 25.3% to 10.8% (p < 0.001). The revascularisation rate
      diminished from 10.4% to 6.3%. The multivariable adjusted hazard ratio (95%
      confidence interval) for invasive coronary angiography during follow-up after CT
      coronary angiography was 0.59 (0.47-0.74) and that for coronary revascularisation
      was 0.66 (0.45-0.97) in 2013 compared to that in 2010. CONCLUSIONS: The radiation
      dose diminished considerably. The reductions in the use of invasive coronary
      angiography and coronary revascularisation could not be explained by changes in
      patient characteristics but are driven by an increased use of perfusion scans in
      combination with increasing use of measurement of functional coronary flow
      reserve.

PMID- 24866567
TI  - Active edge sites in MoSe2 and WSe2 catalysts for the hydrogen evolution
      reaction: a density functional study.
AB  - MoSe2 and WSe2 nanofilms and nanosheets have recently been shown to be active for
      electrochemical H2 evolution (HER). In this work, we used periodic density
      functional theory to investigate the origin of the catalytic activity on these
      materials. We determined the relevant structures of the Mo/W-edges and the Se
      edges under HER conditions and their differential hydrogen adsorption free
      energies. The Mo-edge on MoSe2 and the Se-edge on both MoSe2 and WSe2 are found
      to be the predominantly active facets for these catalysts, with activity
      predicted to be comparable to or better than MoS2. On the other hand, the (0001)
      basal planes are found to be inert. We further explain the enhanced activity at
      the edges in terms of localized edge states, which provide insight into the
      trends in HER activity seen between the two catalysts. Our results thus suggest
      that an optimal catalyst design should maximize the exposure of edge sites.
      Comparisons are also made between the transition metal selenide catalysts and
      their sulfide counterparts in order to understand the consequences of having
      either Mo/W or Se/S atoms. It is found that linear scaling relations describe the
      S/Se binding onto the edge and the H binding onto the S/Se. 

PMID- 24866568
TI  - Developmental changes in postnatal murine intestinal interstitial cell of Cajal
      network structure and function.
AB  - The mammalian gastrointestinal (GI) tract undergoes rapid development during
      early postnatal life in order to transition from a milk to solid diet.
      Interstitial cells of Cajal (ICC) are the pacemaker cells that coordinate smooth
      muscle contractility within the GI tract, and hence we hypothesized that ICC
      networks undergo significant developmental changes during this early postnatal
      period. Numerical metrics for quantifying ICC network structural properties were
      applied on confocal ICC network imaging data obtained from the murine small
      intestine at various postnatal ages spanning birth to weaning. These imaging data
      were also coupled to a biophysically-based computational model to simulate
      pacemaker activity in the networks, to quantify how changes in structure may
      alter function. The results showed a pruning-like mechanism which occurs during
      postnatal development, and the temporal course of this phenomenon was defined.
      There was an initial ICC process overgrowth to optimize network efficiency and
      increase functional output volume. This was followed by a selective retaining and
      strengthening of processes, while others were discarded to further elevate
      functional output volume. Subsequently, new ICC processes were formed and the
      network was adjusted to its adult morphology. These postnatal ICC network
      developmental events may be critical in facilitating mature digestive function. 

PMID- 24866570
TI  - Probabilistic evaluation of predicted force sensitivity to muscle attachment and
      glenohumeral stability uncertainty.
AB  - A major benefit of computational modeling in biomechanics research is its ability
      to estimate internal muscular demands given limited input information. However,
      several assumptions regarding model parameters and constraints may influence
      model outputs. This research evaluated the influence of model parameter
      variability, specifically muscle attachment locations and glenohumeral stability
      thresholds, on predicted rotator cuff muscle force during internal and external
      axial humeral rotation tasks. Additionally, relative sensitivity factors assessed
      which parameters were more contributory to output variability. Modest model
      parameter variation resulted in considerable variability in predicted force, with
      origin-insertion locations being particularly influential. Specifically, the
      scapula attachment site of the subscapularis muscle was important for modulating
      predicted force, with sensitivity factors ranging from alpha=0.2 to 0.7 in a
      neutral position. The largest variability in predicted forces was present for the
      subscapularis muscle, with average differences of 33.0+/-9.6% of normalized
      muscle force (1-99% CI), and a maximal difference of 51% in neutral exertions.
      Infraspinatus and supraspinatus muscles elicited maximal differences of 15.0 and
      20.6%, respectively, between confidence limits. Overall, origin and insertion
      locations were most influential and thus incorporating geometric variation in the
      prediction of rotator cuff muscle forces may provide more representative
      population estimates.

PMID- 24866569
TI  - Transmural variation and anisotropy of microvascular flow conductivity in the rat
      myocardium.
AB  - Transmural variations in the relationship between structural and fluid transport
      properties of myocardial capillary networks are determined via continuum modeling
      approaches using recent three-dimensional (3D) data on the microvascular
      structure. Specifically, the permeability tensor, which quantifies the inverse of
      the blood flow resistivity of the capillary network, is computed by volume
      averaging flow solutions in synthetic networks with geometrical and topological
      properties derived from an anatomically-detailed microvascular data set extracted
      from the rat myocardium. Results show that the permeability is approximately ten
      times higher in the principal direction of capillary alignment (the
      "longitudinal" direction) than perpendicular to this direction, reflecting the
      strong anisotropy of the microvascular network. Additionally, a 30% increase in
      capillary diameter from subepicardium to subendocardium is shown to translate to
      a 130% transmural rise in permeability in the longitudinal capillary direction.
      This result supports the hypothesis that perfusion is preferentially facilitated
      during diastole in the subendocardial microvasculature to compensate for the
      severely-reduced systolic perfusion in the subendocardium. 

PMID- 24866571
TI  - Neuromuscular complexity during gait is not responsive to medication in persons
      with Parkinson's disease.
AB  - The purpose of this study was to investigate the effects of dopaminergic therapy
      on neuromuscular complexity during gait and on the relationship between
      neuromuscular complexity and gait speed in persons with Parkinson's disease (PD).
      Nine persons with PD walked at self-selected speed for 5 min after having
      withdrawn from dopaminergic medication for at least 12 h and while optimally
      medicated. Electromyographic recordings were taken from eight leg muscles
      bilaterally. Non-negative matrix factorization was applied to reduce the
      dimensionality of the electromyographic signals into motor modules. We assessed
      neuromuscular complexity by investigating the number, structure, and timing of
      the modules. We also investigated the influence of dopaminergic medication on the
      relationships between neuromuscular complexity and gait speed. Though gait speed
      increased significantly after medication intake, medication did not affect
      neuromuscular complexity. Neuromuscular complexity was significantly associated
      with gait speed only while the participants were medicated. Thus, the supraspinal
      structures that govern neuromuscular complexity during gait do not appear to be
      solely dopaminergically-influenced in PD. The lack of dopaminergic influence on
      neuromuscular complexity may explain why persons with PD exhibit gait slowness
      even while medicated, and an intervention that restores neuromuscular complexity
      may result in gait speed improvement in PD. 

PMID- 24866572
TI  - Oil-encapsulated nanodroplet array for bio-molecular detection.
AB  - Detection of low abundance biomolecules is challenging for biosensors that rely
      on surface chemical reactions. For surface reaction based biosensors, it require
      to take hours or even days for biomolecules of diffusivities in the order of 10(
      10-11) m2/s to reach the surface of the sensors by Brownian motion. In addition,
      often times the repelling Coulomb interactions between the molecules and the
      probes further defer the binding process, leading to undesirably long detection
      time for applications such as point-of-care in vitro diagnosis. In this work, we
      designed an oil encapsulated nanodroplet array microchip utilizing evaporation
      for pre-concentration of the targets to greatly shorten the reaction time and
      enhance the detection sensitivity. The evaporation process of the droplets is
      facilitated by the superhydrophilic surface and resulting nanodroplets are
      encapsulated by oil drops to form stable reaction chamber. Using this method,
      desirable droplet volumes, concentrations of target molecules, and reaction
      conditions (salt concentrations, reaction temperature, etc.) in favour of fast
      and sensitive detection are obtained. A linear response over 2 orders of
      magnitude in target concentration was achieved at 10 fM for protein targets and
      100 fM for miRNA mimic oligonucleotides.

PMID- 24866574
TI  - Preoperative octreotide treatment of acromegaly: long-term results of a
      randomised controlled trial.
AB  - OBJECTIVE: Randomised studies have demonstrated a beneficial effect of pre
      surgical treatment with somatostatin analogues (SSA) in acromegaly when evaluated
      early postoperatively. The objective of this study was to evaluate the long-term
      surgical cure rates. METHODS: Newly diagnosed patients were randomised to direct
      surgery (n=30) or 6-month pretreatment with octreotide LAR (n=32). The patients
      were evaluated 1 and 5 years postoperatively. Cure was defined as normal IGF1
      levels and by normal IGF1 level combined with nadir GH <2 mU/l in an oral glucose
      tolerance test, all without additional post-operative treatment. A meta-analysis
      using the other published randomised study with long-term analyses on
      preoperative SSA treatment was performed. RESULTS: The proportion of patients
      receiving post-operative acromegaly treatment was equal in the two groups. When
      using the combined criteria for cure, 10/26 (38%) macroadenomas were cured in the
      pretreatment group compared with 6/25 (24%) in the direct surgery group 1 year
      postoperatively (P=0.27), and 9/22 (41%) vs 6/22 (27%) macroadenomas,
      respectively, 5 years postoperatively (P=0.34). In the meta-analysis, 16/45 (36%)
      macroadenomas were cured using combined criteria in the pretreatment group vs
      8/45 (18%) in the direct surgery group after 6-12 months (P=0.06), and 15/41
      (37%) vs 8/42 (19%), respectively, in the long-term (P=0.08). CONCLUSION: This
      study does not prove a beneficial effect of SSA pre-surgical treatment, but in
      the meta-analysis a trend towards significance can be claimed. A potential
      favourable, clinically relevant response cannot be excluded.

PMID- 24866575
TI  - GH receptor isoforms and skeletal fragility in acromegaly.
AB  - OBJECTIVE: Acromegaly is associated with an increased prevalence of vertebral
      fractures (VFs) in close relationship with GH hypersecretion. Two isoforms of the
      GH receptor (GHR) have been identified; the two isoforms differ or not by the
      expression of the protein fragment encoded by exon 3 of the GHR gene. Deletion of
      the exon 3 may influence the functional properties of the GHR and affect fracture
      risk in acromegalic patients. DESIGN: A cross-sectional study was designed to
      investigate the association between the d3-GHR isoform and the prevalence of VFs
      in patients with acromegaly. METHODS: In this study, 109 acromegalic patients
      were included (M/F, 48/61): 73 with controlled/cured acromegaly and 36 with
      active disease. GHR genotype was assessed in each patient. All patients were
      evaluated for VFs and bone mineral density at lumbar spine and hip. Serum IGF1
      levels and bone metabolism markers were measured. A multivariate analysis was
      performed to establish risk factors for VFs in our population. RESULTS: d3-GHR
      carriers showed an increased prevalence of VFs when compared with patients
      expressing full-length GHR (35/55 vs 12/54; P<0.001). The association between GHR
      deletion and VFs was demonstrated both in patients with active disease and in
      those with controlled/cured disease. Out of 35 patients who were prospectively
      evaluated, 13 (37.1%) developed incident VFs. The incidence of VFs was
      significantly higher in patients for whom the GHR gene has been deleted when
      compared with those harboring the fl gene (P=0.04). In multivariate analysis,
      male sex (odds ratio (OR), 3.250; P=0.041), IGF1 levels (OR, 1.183; P=0.031),
      length of active diseases (OR, 1.038; P=0.001), and d3-GHR genotype (OR, 3.060;
      P=0.015) were all confirmed as risk factors of VFs in our population.
      CONCLUSIONS: This study suggests for the first time that exon 3 deletion of GHR
      may predispose patients with active and controlled acromegaly to a higher risk of
      VFs.

PMID- 24866573
TI  - Objectively assessed physical activity and subsequent health service use of UK
      adults aged 70 and over: a four to five year follow up study.
AB  - OBJECTIVES: To examine the associations between volume and intensity of older
      peoples' physical activity, with their subsequent health service usage over the
      following four to five years. STUDY DESIGN: A prospective cohort design using
      baseline participant characteristics, objectively assessed physical activity and
      lower limb function provided by Project OPAL (Older People and Active Living).
      OPAL-PLUS provided data on numbers of primary care consultations, prescriptions,
      unplanned hospital admissions, and secondary care referrals, extracted from
      medical records for up to five years following the baseline OPAL data collection.
      PARTICIPANTS AND DATA COLLECTION: OPAL participants were a diverse sample of 240
      older adults with a mean age of 78 years. They were recruited from 12 General
      Practitioner surgeries from low, middle, and high areas of deprivation in a city
      in the West of England. Primary care consultations, secondary care referrals,
      unplanned hospital admissions, number of prescriptions and new disease diagnoses
      were assessed for 213 (104 females) of the original 240 OPAL participants who had
      either consented to participate in OPAL-PLUS or already died during the follow-up
      period. RESULTS: In regression modelling, adjusted for socio-economic variables,
      existing disease, weight status, minutes of moderate-to-vigorous physical
      activity (MVPA) per day predicted subsequent numbers of prescriptions. Steps
      taken per day and MVPA also predicted unplanned hospital admissions, although the
      strength of the effect was reduced when further adjustment was made for lower
      limb function. CONCLUSIONS: Community-based programs are needed which are
      successful in engaging older adults in their late 70s and 80s in more walking,
      MVPA and activity that helps them avoid loss of physical function. There is a
      potential for cost savings to health services through reduced reliance on
      prescriptions and fewer unplanned hospital admissions.

PMID- 24866576
TI  - Stimulated thyroglobulin level at ablation in differentiated thyroid cancer: the
      impact of treatment preparation modalities and tumor burden.
AB  - OBJECTIVE: In patients with differentiated thyroid cancer (DTC), the stimulated
      serum thyroglobulin (Tg) level at radioiodine ablation is a known predictive
      factor of persistent disease. This prognostic value is based on data obtained
      after thyroid hormone withdrawal (THW), but little is known about this prognostic
      value after recombinant human TSH (rhTSH) stimulation and about the relationship
      between the stimulated Tg level and the burden of persistent tumor. We aimed to
      assess the impact of both radioiodine preparation modalities and persistent tumor
      burden on stimulated Tg levels. DESIGN AND METHODS: The stimulated Tg level was
      measured at radioablation in 308 consecutive DTC patients without serum Tg
      antibodies. Of these, 123 (40%) were prepared with rhTSH and 185 with THW. Post
      ablation scintigraphy included total-body scan and neck and thorax single photon
      emission computed tomography with computed tomography (SPECT-CT). During a mean
      follow-up of 43 months, persistent/recurrent disease (PRD) was found in 56
      patients (18%). PRD was considered structural in the presence of lesions >1 cm
      and nonstructural otherwise. RESULTS: Nonstructural PRD was more frequent in the
      rhTSH group than in the THW group (64 vs 26%, P=0.01). Stimulated Tg levels were
      lower after rhTSH than after THW in patients with (13.5 vs 99.5 ng/ml, P<0.01)
      and without (1.2 vs 3.2 ng/ml, P<0.001) PRD. Also, Tg levels were lower in
      nonstructural disease than in structural disease in both rhTSH (3.8 vs 127.0
      ng/ml, P<0.01) and THW (13.0 vs 143.5 ng/ml, P<0.0001) patients. The best Tg
      cutoff to predict PRD was 2.8 in rhTSH and 28 ng/ml in THW patients. CONCLUSION:
      Both radioiodine preparation modalities and the burden of persistent tumor affect
      the stimulated Tg level at ablation.

PMID- 24866583
TI  - Myocardial blood flow and its transit time, oxygen utilization, and efficiency of
      highly endurance-trained human heart.
AB  - Highly endurance-trained athlete's heart represents the most extreme form of
      cardiac adaptation to physical stress, but its circulatory alterations remain
      obscure. In the present study, myocardial blood flow (MBF), blood mean transit
      time (MTT), oxygen extraction fraction (OEF) and consumption (MVO2), and
      efficiency of cardiac work were quantified in highly trained male endurance
      athletes and control subjects at rest and during supine cycling exercise using
      [(15)O]-labeled radiotracers and positron emission tomography. Heart rate and MBF
      were lower in athletes both at rest and during exercise. OEF increased in
      response to exercise in both groups, but was higher in athletes (70 +/- 21 vs. 63
      +/- 11 % at rest and 86 +/- 13 vs. 73 +/- 10 % during exercise). MTT was longer
      and vascular resistance higher in athletes both at rest and during exercise, but
      arterial content of 2,3-diphosphoglycerate (oxygen affinity) was unchanged. MVO2
      per gram of myocardium trended (p = 0.08) lower in athletes both at rest and
      during exercise, while myocardial efficiency of work and MVO2 per beat were not
      different between groups. Arterial levels of free fatty acids were ~twofold
      higher in athletes likely leading to higher myocardial fatty acid oxidation and
      hence oxygen cost, which may have blunted the bradycardia-induced decrease in
      MVO2. Finally, the observed group differences in MBF, OEF, MTT and vascular
      resistance remained significant also after they were controlled for differences
      in MVO2. In conclusion, in highly endurance-trained human heart, increased
      myocardial blood transition time enables higher oxygen extraction levels with a
      lower myocardial blood flow and higher vascular resistance. These physiological
      adaptations to exercise training occur independently of the level of oxygen
      consumption and together with training-induced bradycardia may serve as
      mechanisms to increase functional reserve of the human heart.

PMID- 24866585
TI  - YM155 sensitizes triple-negative breast cancer to membrane-bound TRAIL through
      p38 MAPK- and CHOP-mediated DR5 upregulation.
AB  - Because available treatments have limited efficacy in triple-negative breast
      cancer (TNBC), the identification of new therapeutic strategies to improve
      patients' outcome is urgently needed. In our study, we investigated the effects
      of the administration of the small molecule selective survivin suppressant YM155,
      alone or in association with CD34+ cells transduced with a replication-deficient
      adenovirus encoding the human tumor necrosis factor-related apoptosis-inducing
      ligand (TRAIL) gene (CD34-TRAIL+ cells), in three TNBC cell models. YM155
      exposure significantly impaired TNBC cell growth and selectively modulated
      survivin expression at both mRNA and protein level. In addition, co-culturing
      YM155-treated TNBC cells with CD34-TRAIL+ cells resulted in markedly increased
      cytotoxic effect and apoptotic response in comparison with single treatments.
      Such a chemosensitizing effect was observed only in TNBC cells inherently
      expressing DR5 and relied on the ability of YM155 to upregulate DR5 expression
      through a p38 MAPK- and CHOP-dependent mechanism. YM155/CD34-TRAIL+ combination
      also showed a significant inhibitory effect on the growth of DR5-expressing TNBC
      cells following xenotransplantation into NOD/SCID mice, in the absence of
      toxicity. Overall, our data (i) provide, for the first time, evidence that YM155
      sensitizes TNBC cells to CD34-TRAIL+ cells-induced apoptosis by a mechanism
      involving the downregulation of survivin and the simultaneous p38 MAPK- and CHOP
      mediated upregulation of DR5, and (ii) suggest the combination of YM155 with
      TRAIL-armed CD34+ progenitor cells as a promising therapeutic option for patients
      with TNBC expressing DR5. 

PMID- 24866591
TI  - Polyploidy and small RNA regulation of cotton fiber development.
AB  - Cotton is not only the most important source of renewal textile fibers, but also
      an excellent model for studying cell fate determination and polyploidy effects on
      gene expression and evolution of domestication traits. The combination of A and D
      progenitor genomes into allotetraploid cotton induces intergenomic interactions
      and epigenetic effects, leading to the unequal expression of homoeologous genes.
      Small RNAs regulate the expression of transcription and signaling factors related
      to cellular growth, development and adaptation. An example is miRNA-mediated
      preferential degradation of homoeologous mRNAs encoding MYB-domain transcription
      factors that are required for the initiation of leaf trichomes in Arabidopsis and
      of seed fibers in cotton. This example of coevolution between small RNAs and
      their homoeologous targets could shape morphological traits such as fibers during
      the selection and domestication of polyploid crops. 

PMID- 24866589
TI  - Influence of ranibizumab treatment on the extracellular matrix in patients with
      neovascular age-related macular degeneration.
AB  - BACKGROUND: We know the influence of the intravitreal anti-vascular endothelial
      growth factor (VEGF) injections on the choroidal neovascularization in the course
      of exudative age-related macular degeneration (AMD). However, the influence of
      the ranibizumab therapy in question on the extracellular matrix (ECM) remains
      unknown. We aimed to estimate the influence of Lucentis intravitreal injections
      on the gene expression of structural components of the extracellular matrix in
      patients with neovascular AMD. MATERIAL AND METHODS: Patients with subfoveal
      localization of neovascularization in AMD, which was clinically active and
      observed using optical coherence tomography, were treated with ranibizumab (0.5
      mg/0.05 mL) in accordance with the PrONTO scheme. Total RNA was extracted from
      peripheral blood mononuclear cells, and an oligonucleotide microarray technique
      enabled comparison of the expression level of genes encoding collagens, elastin,
      and laminins in AMD patients compared to control subjects. RESULTS: After 3
      intravitreal injections of ranibizumab (Lucentis), COL1A1 and COL6A1 genes showed
      increased expression, whereas decreased expression mainly occurred for the
      following genes: COL4A5, COL11A1, OL4A6C, LAMB4, and LAMC2. CONCLUSIONS: Anti
      VEGF local therapy influences the gene expression of structural components of the
      ECM as measured from blood samples. The loading dose of ranibizumab for the
      retina changes the expression of collagen and laminin genes, but does not
      influence the expression of the elastin gene.

PMID- 24866592
TI  - Is Lys-NE-acetylation the next big thing in post-translational modifications?
AB  - Lys-N(E)-acetylation (PKA) has recently ascended from a post-translational
      modification (PTM) of limited distribution to one approaching the abundance of O
      phosphorylation. Thousands of KAC proteins have been identified in Archaea,
      bacteria, and Eukarya, and the KAC system of acetyltransferases, deacetylases,
      and binding proteins is superficially comparable with the kinases, phosphatases,
      and phospho- (P-)protein binding-proteins of O-phosphorylation. Herein, we
      describe recent results and compare several aspects of these two major systems of
      PTM in plants. 

PMID- 24866594
TI  - Performance on a functional motor task is enhanced by sleep in middle-aged and
      older adults.
AB  - BACKGROUND AND PURPOSE: Although sleep has been shown to enhance motor skill
      learning, it remains unclear whether sleep enhances learning of a functional
      motor task in middle-aged and older individuals. The purpose of this study was to
      examine whether sleep enhances motor learning of a functional motor task in
      middle-aged and older adults. METHODS: Twenty middle-aged and 20 older
      individuals were randomly assigned to either the sleep condition or the no-sleep
      condition. Participants in the sleep condition practiced a novel walking task in
      the evening, and returned the following morning for retesting. Participants in
      the no-sleep condition practiced the walking task in the morning and returned the
      same day in the evening for a retest. Outcome measures included time around the
      walking path and spatiotemporal gait parameters. RESULTS: Only the middle-aged
      and older adults in the sleep condition demonstrated significant off-line
      improvement in performance, measured as a decline in time to walk around the
      novel path and improvement in spatiotemporal gait parameters. The middle-aged and
      older adults in the no-sleep condition failed to demonstrate off-line
      improvements in performance of this functional task. CONCLUSIONS: This is the
      first study to provide evidence that sleep facilitates learning a clinically
      relevant functional motor task in middle-aged and older adults. Because many
      neurologic conditions occur in the middle-aged and older adults and sleep issues
      are very prevalent in many neurologic conditions, it is imperative that physical
      therapists consider sleep as a factor that may impact motor learning and recovery
      in these individuals. VIDEO ABSTRACT AVAILABLE: (See Video, Supplemental Digital
      Content 1, http://links.lww.com/JNPT/A73) for more insights from the authors.

PMID- 24866595
TI  - miRNA-34a suppresses cell proliferation and metastasis by targeting CD44 in human
      renal carcinoma cells.
AB  - PURPOSE: We investigated the potential functions of miR-34a in CD44
      transcriptional complexes in renal cell carcinoma. MATERIALS AND METHODS: We
      detected miR-34a expression by quantitative real-time polymerase chain reaction.
      Oligonucleotides were used to over express miR-34a. Cell proliferation and
      xenograft assays, colony formation and flow cytometry were done to examine
      effects on cancer cell proliferation in vitro and in vivo. Luciferase assay was
      performed to verify the precise target of miR-34a. RESULTS: Promoter methylation
      contributed to miR-34a loss in the ACHN, 786-O and SN12PM6 renal carcinoma cell
      lines. Ectopic over expression of miR-34a restrained cell growth, tube formation
      and migration/invasion, and significantly suppressed the growth of renal
      carcinoma xenografts and metastasis in nude mice. Dual luciferase assay revealed
      that CD44 was a direct target of miR-34a in renal cancer cells and CD44 knockdown
      by RNAi in renal cancer cells suppressed tumor progression. In contrast, CD44
      ectopic expression partially reversed the antitumor effects of miR-34a in renal
      cancer cells. CONCLUSIONS: Our findings indicate that miR-34a targets CD44 in
      renal cancer cells and suppresses renal cancer cell growth, tube formation and
      metastasis in vitro and in vivo. Thus, miR-34a may be a potential molecular
      target for novel therapeutic strategies for clear cell renal carcinoma.

PMID- 24866596
TI  - A high throughput, minimally invasive, ultrasound guided model for the study of
      catheter associated urinary tract infections and device encrustation in mice.
AB  - PURPOSE: Catheter associated urinary tract infections are one of the most common
      health care associated infections. The condition is frequently complicated by
      encrustation, which blocks the catheter lumen. Preclinical research is limited by
      the lack of relevant high throughput and cost-effective animal models. Current
      models are restricted to female mice, associated with major transurethral loss of
      catheter materials during micturition, highly invasive and complex. We present an
      ultrasound guided, minimally invasive model that enables catheter associated
      urinary tract infection and catheter encrustation studies in each mouse gender.
      MATERIALS AND METHODS: Catheter segments (4 mm) were implanted in murine bladders
      percutaneously in 15 males and 5 females, and transurethrally in 15 females using
      the Seldinger technique under ultrasound guidance. Proteus mirabilis was
      instilled intraluminally. Catheter encrustation was monitored by ultrasound.
      Bacteria were quantified in urine, and catheters and encrustation were analyzed
      on day 6 or 21. RESULTS: Percutaneous and transurethral catheter implantations
      were performed in a mean +/- SE 3.6 +/- 0.8 vs 2.5 +/- 0.5 minutes in all mice.
      Ultrasound confirmed that 100% and 66% of implanted catheters, respectively,
      remained indwelling during the study period. Catheter encrustation developed in
      P. mirabilis infected urine 48 hours after instillation and an increase with time
      was detected by ultrasound. Fourier transform spectroscopy of the encrustation
      confirmed a typical struvite spectrum. Control catheters remained sterile during
      21 days. CONCLUSIONS: Our minimally invasive, reproducible percutaneous technique
      is suitable for studying catheter associated urinary tract infection in each
      gender. Infecting urine with P. mirabilis generates a preclinical model of
      catheter encrustation within 3 days. The progression of encrustation can be
      monitored in vivo by ultrasound, making this image based model suitable for
      assessing novel antibacterial and anti-encrustation therapies.

PMID- 24866597
TI  - Prospective evaluation of magnetic resonance imaging guided in-bore prostate
      biopsy versus systematic transrectal ultrasound guided prostate biopsy in biopsy
      naive men with elevated prostate specific antigen.
AB  - PURPOSE: Magnetic resonance imaging guided biopsy is increasingly performed to
      diagnose prostate cancer. However, there is a lack of well controlled,
      prospective trials to support this treatment method. We prospectively compared
      magnetic resonance imaging guided in-bore biopsy with standard systematic
      transrectal ultrasound guided biopsy in biopsy naive men with increased prostate
      specific antigen. MATERIALS AND METHODS: We performed a prospective study in 132
      biopsy naive men with increased prostate specific antigen (greater than 4 ng/ml).
      After 3 Tesla functional multiparametric magnetic resonance imaging patients were
      referred for magnetic resonance imaging guided in-bore biopsy of prostate lesions
      (maximum 3) followed by standard systematic transrectal ultrasound guided biopsy
      (12 cores). We analyzed the detection rates of prostate cancer and significant
      prostate cancer (greater than 5 mm total cancer length or any Gleason pattern
      greater than 3). RESULTS: A total of 128 patients with a mean +/- SD age of 66.1
      +/- 8.1 years met all study requirements. Median prostate specific antigen was
      6.7 ng/ml (IQR 5.1-9.0). Transrectal ultrasound and magnetic resonance imaging
      guided biopsies provided the same 53.1% detection rate, including 79.4% and
      85.3%, respectively, for significant prostate cancer. Magnetic resonance imaging
      and transrectal ultrasound guided biopsies missed 7.8% and 9.4% of clinically
      significant prostate cancers, respectively. Magnetic resonance imaging biopsy
      required significantly fewer cores and revealed a higher percent of cancer
      involvement per biopsy core (each p <0.01). Combining the 2 methods provided a
      60.9% detection rate with an 82.1% rate for significant prostate cancer.
      CONCLUSIONS: Magnetic resonance imaging guided in-bore and systematic transrectal
      ultrasound guided biopsies achieved equally high detection rates in biopsy naive
      patients with increased prostate specific antigen. Magnetic resonance imaging
      guided in-bore biopsies required significantly fewer cores and revealed a
      significantly higher percent of cancer involvement per biopsy core.

PMID- 24866598
TI  - Incidence of infectious complications after extracorporeal shock wave lithotripsy
      in patients without associated risk factors.
AB  - PURPOSE: We determined the incidence of infectious complications (asymptomatic
      bacteriuria, urinary tract infection and urosepsis) in patients without
      associated risk factors treated with extracorporeal shock wave lithotripsy.
      MATERIALS AND METHODS: We performed an observational, prospective cohort study
      between October 2010 and June 2013. We included all patients without risk factors
      who were treated with extracorporeal shock wave lithotripsy for kidney or
      ureteral lithiasis. All patients underwent urine culture 5 days before the
      procedure. Another urine culture was performed 7 days after lithotripsy. No
      patient received antibiotics. RESULTS: Initially 366 patients with a mean +/- SD
      age of 53 +/- 13 years were enrolled in the study. A total of 64 patients (17.5%)
      underwent extracorporeal shock wave lithotripsy with a previously placed Double
      J(r) stent. After lithotripsy urine culture was positive in 20 patients (5.8%),
      of whom 4 (1.2%) presented with symptomatic urinary infection and the remaining
      4.6% showed no symptoms. Urosepsis did not develop in any case. In our study
      patient age was an independent risk factor for bacteriuria after lithotripsy.
      CONCLUSIONS: The incidence of infectious complications after extracorporeal shock
      wave lithotripsy in patients without risk factors is low. This leads us to
      conclude that without defined risk factors antibiotic prophylaxis is not
      justified. Also, elderly patients were more at risk for bacteriuria after
      extracorporeal shock wave lithotripsy and, thus, for a possible infectious
      complication.

PMID- 24866599
TI  - The surgical management of kidney stone disease: a population based time series
      analysis.
AB  - PURPOSE: We evaluate population based trends in the use of extracorporeal shock
      wave lithotripsy, ureteroscopy and percutaneous nephrolithotomy during the last
      20 years, as well as assess the re-treatment rate and morbidity from treatment
      over time. MATERIALS AND METHODS: Using administrative databases in the province
      of Ontario, Canada, a population based cross-sectional time series analysis was
      performed between July 1, 1991 and December 31, 2010. All extracorporeal shock
      wave lithotripsy, ureteroscopy and percutaneous nephrolithotomy procedures were
      identified, along with all hospital readmissions and emergency department visits
      within 7 days of treatment. The primary outcome was treatment use, and secondary
      outcomes were the need for ancillary treatment and hospital readmission or
      emergency department visit after treatment. Exponential smoothing and
      autoregressive integrated moving average (ARIMA) models were used to assess
      trends over time. RESULTS: We identified 194,781 kidney stone treatments
      performed during the study period. Time series modeling revealed a significant
      increase in the use of ureteroscopy over time (25% to 59% of all procedures, p
      <0.0001) and a reciprocal decrease in the use of extracorporeal shock wave
      lithotripsy (69% to 34% of all procedures, p <0.0001). A corresponding
      significant decrease in the need for ancillary treatment over time (23% to 15%, p
      <0.0001) and increase in the need for hospital readmission (7% to 11%, p <0.0001)
      or emergency department visit (7% to 11%, p=0.0024) after treatment were also
      demonstrated. CONCLUSIONS: Our population based study demonstrates a shift in the
      treatment paradigm with increased use of ureteroscopy over time and a reciprocal
      decrease in the use of extracorporeal shock wave lithotripsy. We also observed a
      corresponding decrease in ancillary treatment and increase in posttreatment
      morbidity over time.

PMID- 24866600
TI  - The sonographic "bright band sign" of splenic infarction.
AB  - OBJECTIVES: To evaluate the frequency of the "bright band sign" in patients with
      splenic infarcts as well as control patients and to thereby assess whether the
      bright band sign has potential utility as a sonographic sign of splenic
      infarction. METHODS: Using an electronic search engine and image review, 37
      patients were retrospectively identified with noncystic parenchymal splenic
      infarcts on sonography. Nineteen abnormal control patients with noninfarcted
      splenic lesions on sonography and 100 normal control patients with
      sonographically normal spleens were also identified. The sonographic appearance
      of each splenic lesion was evaluated by 2 reviewers and assessed for the bright
      band sign, defined as thin specular reflectors perpendicular to the sound beam
      within hypoechoic parenchymal lesions, and for the presence or absence of the
      classic sonographic appearance of splenic infarction. Possible histologic
      counterparts of the bright band sign were assessed in archival infarct specimens.
      RESULTS: The bright band sign was present in 34 (91.9%; 95% confidence interval
      [CI], 78.1%-98.3%) of 37 patients with splenic infarcts on sonography, including
      12 (85.7%; 95% CI, 57.2%-98.2%) of 14 with classic and 22 (95.7%; 95% CI, 78.1%
      99.9%) of 23 with nonclassic infarct appearances. No normal or abnormal control
      patients had the bright band sign. Histologic sections suggested that preserved
      splenic trabeculae within infarcts may generate the bright band sign.
      CONCLUSIONS: The bright band sign is a potentially useful sonographic sign of
      splenic infarction, which may confer additional sensitivity and specificity and
      may be particularly helpful with infarcts having nonclassic appearances.

PMID- 24866602
TI  - Effects of low-intensity ultrasound on gramicidin D-induced erythrocyte edema.
AB  - OBJECTIVES: To determine whether low-intensity ultrasound (US) can reduce red
      blood cell (RBC) edema and, if so, whether the US activity is associated with
      aquaporin 1 (AQP-1), a water channel in the cell membrane. METHODS: Red blood
      cell edema was induced by gramicidin D treatment at 40 ng/mL for 20 minutes and
      evaluated by a hematocrit assay. Low-intensity continuous wave US at 1 MHz was
      applied to RBCs for the last 10 minutes of gramicidin D treatment. To determine
      whether US activity was associated with AQP-1, RBCs were treated with 40 MUM
      mercuric chloride (HgCl(2)), an AQP-1 inhibitor, for 20 minutes at the time of
      gramicidin D treatment. Posttreatment morphologic changes in RBCs were observed
      by actin staining with phalloidin. RESULTS: Red blood cell edema increased
      significantly with gramicidin D at 20 (1.8%), 40 (6.7%), 60 (16.7%), and 80
      (11.3%) ng/mL, reaching a peak at 60 ng/mL, compared to the control group (20
      ng/mL, P = .019; 40, 60, and 80 ng/mL, P < .001). No significant RBC hemolysis
      was observed in any group. Edema induced by gramicidin D at 40 ng/mL was
      significantly reduced by US at 30 (3.4%; P = .003), 70 (4.4%; P = .001), and 100
      (2.9%; P = .001) mW/cm(2). Subsequent experiments showed that edema reduction by
      US ranged from 7% to 10%. Cotreatment with HgCl(2) partially reversed the US
      effect and showed a significantly different level of edema compared to gramicidin
      D-alone and US-cotreated groups (P = .001). These results were confirmed by
      microscopic observation of RBC morphologic changes. CONCLUSIONS: Low-intensity US
      could reduce gramicidin D-induced RBC edema, and its effect appeared to at least
      partly involve regulation of AQP-1 activity. These results suggest that low
      intensity US can be used as an alternative treatment to control edema and related
      disorders.

PMID- 24866601
TI  - Contrast-enhanced sonography for detection of secondary lymph nodes in a melanoma
      tumor animal model.
AB  - OBJECTIVES: To investigate the use of contrast-enhanced ultrasound imaging (US)
      for detection of secondary lymph nodes (LNs) in a naturally occurring melanoma
      swine model compared to surgery and pathologic assessment. METHODS: Twenty-seven
      Sinclair swine were studied. The perfluorobutane microbubble contrast agent
      Sonazoid (GE Healthcare, Oslo, Norway) was administered (1.0 mL total dose)
      around the melanoma, and contrast-enhanced US was used to localize contrast
      enhanced sentinel lymph nodes (SLNs). Then Sonazoid (dose, 0.25-1.0 mL) was
      injected into the SLNs to detect contrast-enhanced efferent lymphatic channels
      and secondary LNs. After peritumoral injection of blue dye, a surgeon (blinded to
      the contrast-enhanced US results) performed a radical LN dissection. Contrast
      enhanced US was used to guide removal of any enhanced secondary LNs left after
      radical LN dissection. Clustered conditional logistic regression analyzed the
      benefit of contrast-enhanced US-directed secondary LN dissection over radical LN
      dissection using pathologic findings as the reference standard. RESULTS: A total
      of 268 secondary LNs were resected, with 59 (22%) containing metastases. Contrast
      enhanced US detected 92 secondary LNs; 248 were identified by radical LN
      dissection; and 68 were identified by both methods. Metastases were detected in
      20% (51 of 248) and 40% (37 of 92) of the secondary LNs identified by radical LN
      dissection and contrast-enhanced US, respectively. Thus, secondary LNs detected
      by contrast-enhanced US were nearly 5 times more likely to contain metastases
      than secondary LNs removed by radical LN dissection (odds ratio, 4.8; P < .0001).
      Twenty-two of the 180 secondary LNs (12%) identified only by radical LN
      dissection contained metastases, whereas contrast-enhanced US identified 20
      secondary LNs after the surgeon completed the radical LN dissection, of which 8
      (40%) contained metastases. CONCLUSIONS: Secondary LNs can be detected by using
      contrast-enhanced US after injection of Sonazoid into SLNs. Secondary LNs
      detected with contrast-enhanced US are significantly more likely to contain
      metastases than those removed by radical LN dissection.

PMID- 24866603
TI  - Enhanced lesion-to-bubble ratio on ultrasonic Nakagami imaging for monitoring of
      high-intensity focused ultrasound.
AB  - OBJECTIVES: This work explored the feasibility of using ultrasonic Nakagami
      imaging to enhance the contrast between thermal lesions and bubbles induced by
      high-intensity focused ultrasound (US) in a transparent tissue-mimicking phantom
      at different acoustic power levels. METHODS: The term "lesion-to-bubble ratio"
      was proposed and defined as the ratio of the scattered power from the thermal
      lesion to the scattered power from the bubbles calculated in the various
      monitoring of images for high-intensity focused US. Two-dimensional
      radiofrequency data backscattered from the exposed region were captured by a
      modified diagnostic US scanner to estimate the Nakagami statistical parameter, m,
      and reconstruct the ultrasonic B-mode images and Nakagami parameter images. The
      dynamic changes in the lesion-to-bubble ratio over the US exposure procedure were
      calculated simultaneously and compared among video photos, B-mode images, and
      Nakagami images for monitoring of high-intensity focused US. RESULTS: After a
      small thermal lesion was induced by high-intensity focused US in the phantom, the
      lesion-to-bubble ratio values corresponding to the video photo, B-mode image, and
      Nakagami image were 5.3, 1, and 9.8 dB, respectively. When a large thermal lesion
      appeared in the phantom, the ratio values increased to 7.2, 3, and 14 dB. During
      US exposure, the ratio values calculated for the video photo, B-mode image, and
      Nakagami image began to increase gradually and rose to peak values of 8.3, 2.9,
      and 14.8 dB at the end of the US exposure. CONCLUSIONS: This preliminary study on
      a tissue-mimicking phantom suggests that Nakagami imaging may have a potential
      use in enhancing the lesion-to-bubble ratio for monitoring high-intensity focused
      US. Further studies in vivo and in vitro will be needed to evaluate the potential
      applications for high-intensity focused US.

PMID- 24866604
TI  - Exploring carotid sonographic parameters associated with stroke risk among
      hypertensive stroke patients compared to hypertensive controls.
AB  - OBJECTIVES: Globally, and particularly in low- and middle-income countries, the
      prevalence of hypertension is increasing with a consequent rise in the burden of
      stroke. There is a need to identify biomarkers of stroke, which can be used to
      design stroke prevention programs in these populations. Sonography is an
      affordable and widely available imaging modality that is ideal for resource-poor
      countries. We conducted a case-control study to identify carotid sonographic
      parameters that may be associated with stroke risk among hypertensive patients.
      METHODS: Selected demographic, clinical, and laboratory characteristics were
      collected from 135 consecutive African hypertensive stroke patients and compared
      with 117 age and sex-matched hypertensive patients with no clinical evidence of
      stroke, transient ischemic attacks, or ischemic heart disease (controls). The
      luminal diameter, intima-media thickness, peak systolic velocity (PSV), and end
      diastolic velocity (EDV) of the common and internal carotid arteries were
      measured in all participants, and other carotid parameters, including pulsatility
      and resistive indices, were derived. Univariate, bivariate, and multivariate
      analyses were performed RESULTS: Among hypertensive patients, carotid parameters
      significantly (P < .05) associated with stroke included a higher diameter and
      intima-media thickness as well as a lower PSV and EDV in the common carotid and
      proximal internal carotid arteries. However, the diameter (>6.3 mm; adjusted odds
      ratio [OR], 8.91; 95% confidence interval [CI], 2.18-36.34; P = .002) and EDV
      (>21 cm/s; adjusted OR, 0.15; 95% CI, 0.03-0.71; P = .017) of the common carotid
      artery were the only parameters associated with stroke in multivariate analysis.
      CONCLUSIONS: Among hypertensive patients, the common carotid artery diameter and
      EDV are significantly associated with stroke risk. These findings have
      implications for development and evaluation of stroke prevention programs.

PMID- 24866605
TI  - Quality assurance in ultrasound screening for hepatocellular carcinoma using a
      standardized phantom and standard clinical images: a 3-year national
      investigation in Korea.
AB  - OBJECTIVES: The purpose of this study was to investigate the quality of
      ultrasound (US) imaging for hepatocellular carcinoma screening. METHODS: The
      investigation was performed at all medical institutes participating in the
      National Cancer Screening Program in Korea. For assessment of personnel, we
      inquired who was performing the US screenings. For phantom image evaluation, the
      dead zone, vertical and horizontal measurements, axial and lateral resolution,
      sensitivity, and gray scale/dynamic range were evaluated. For clinical image
      evaluation, US images of patients were evaluated in terms of the standard images,
      technical information, overall image quality, appropriateness of depth, foci,
      annotations, and the presence of any artifacts. RESULTS: Failure rates for
      phantom and clinical image evaluations at general hospitals, smaller hospitals,
      and private clinics were 20.9%, 24.5%, 24.1% and 5.5%, and 14.8% and 9.5%,
      respectively. No statistically significant difference was observed in the failure
      rates for the phantom images among groups of different years of manufacture. For
      the clinical image evaluation, the results of radiologists were significantly
      better than those of other professional groups (P = .0001 and .0004 versus
      nonradiology physicians and nonphysicians, respectively). The failure rate was
      also higher when the storage format was analog versus digital (P < .001).
      CONCLUSIONS: Approximately 20% of US scanners failed the phantom image
      evaluation. The year of scanner manufacture was not significantly associated with
      the results of the phantom image evaluation. The quality of the clinical images
      obtained by radiologists was the best.

PMID- 24866606
TI  - Do emergency ultrasound fellowship programs impact emergency medicine residents'
      ultrasound education?
AB  - OBJECTIVES: Recent years have seen a rapid proliferation of emergency ultrasound
      (EUS) programs in the United States. To date, there is no evidence supporting
      that EUS fellowships enhance residents' ultrasound (US) educational experiences.
      The purpose of this study was to determine the impact of EUS fellowships on
      emergency medicine (EM) residents' US education. METHODS: We conducted a cross
      sectional study at 9 academic medical centers. A questionnaire on US education
      and bedside US use was pilot tested and given to EM residents. The primary
      outcomes included the number of US examinations performed, scope of bedside US
      applications, barriers to residents' US education, and US use in the emergency
      department. The secondary outcomes were factors that would impact residents' US
      education. The outcomes were compared between residency programs with and without
      EUS fellowships. RESULTS: A total of 244 EM residents participated in this study.
      Thirty percent (95% confidence interval, 24%-35%) reported they had performed
      more than 150 scans. Residents in programs with EUS fellowships reported
      performing more scans than those in programs without fellowships (P = .04).
      Significant differences were noted in most applications of bedside US between
      residency programs with and without fellowships (P < .05). There were also
      significant differences in the barriers to US education between residency
      programs with and without fellowships (P < .05). CONCLUSIONS: Emergency US
      fellowship programs had a positive impact on residents' US educational
      experiences. Emergency medicine residents performed more scans overall and also
      used bedside US for more advanced applications in programs with EUS fellowships.

PMID- 24866607
TI  - Ultrasound for internal medicine physicians: the future of the physical
      examination.
AB  - OBJECTIVES: With the advent of compact ultrasound (US) devices, it is easier for
      physicians to enhance their physical examinations through the use of US. However,
      although this new tool is widely available, few internal medicine physicians have
      US training. This study sought to understand physicians' baseline knowledge and
      skill, provide education in US principles, and demonstrate that proper use of
      compact US devices is a skill that can be quickly learned. METHODS: Training was
      performed at the Mayo Clinic in June 2010 and June 2011. The participants
      consisted of internal medicine residents. The workshop included didactics and
      hands-on US experiences with human and cadaver models in a simulation center.
      Pretests and posttests of residents' knowledge, attitudes, and skills with US
      were completed. We reassessed the 2010 group in the spring of 2012 with a long
      term retention survey for knowledge and confidence in viewing images. RESULTS: A
      total of 136 interns completed the workshop. Thirty-nine residents completed the
      long-term retention survey. Posttest assessments showed a statistically
      significant improvement in the knowledge of US imaging, confidence in identifying
      structures, image identification, and image acquisition (P < .0001). In the long
      term retention study, knowledge of US imaging and confidence in identifying
      structures did decline. CONCLUSIONS: This educational intervention resulted in
      improvement in US knowledge and image acquisition. However, the knowledge
      diminished over time, suggesting that further education is needed if US is to
      become an important component of internal medicine training and practice.

PMID- 24866608
TI  - Role of [18F]fluorodeoxyglucose positron emission tomography-computed tomography,
      sonography, and sonographically guided fine-needle aspiration biopsy in the
      diagnosis of axillary lymph nodes in patients with breast cancer: comparison of
      diagnostic performance.
AB  - OBJECTIVES: The aim of this study was to compare the diagnostic performance of
      [(18)F]fluorodeoxyglucose (FDG) positron emission tomography-computed tomography
      (PET-CT) with that of sonography and sonographically guided fine-needle
      aspiration (FNA) for determining the preoperative axillary lymph node (ALN)
      status and to evaluate the factors related to false-negative PET-CT, sonographic,
      and FNA results in ALN staging of invasive ductal carcinoma. METHODS: From March
      2009 to July 2012, 226 patients had a diagnosis of primary breast cancer. Among
      these patients, 107 constituted the study population after exclusion of
      transferred patients and patients with breast cancer other than invasive ductal
      carcinoma. The diagnostic performance of the modalities was compared with
      pathologic reports. Univariate and multivariate analyses were used to evaluate
      the relationship between clinicopathologic factors (symptoms, T stage, hormone
      receptors, and histologic grade), false-negative results, and true-negative
      results on PET-CT, sonography, and FNA. RESULTS: Of the 107 patients, 45 (42.1%)
      had positive results on final pathologic analysis of ALNs. Sonographically guided
      FNA had a significantly higher specificity, positive predictive value, accuracy,
      and area under the receiver operating characteristic curve than sonography and
      PET-CT (P < .01). When sonography and PET-CT were combined, the sensitivity was
      significantly improved (P = .019) compared with sonography alone. When FNA and
      PET-CT were combined, the sensitivity and negative predictive value were
      significantly increased compared with each modality (P < .01). CONCLUSIONS:
      Sonographically guided FNA was found to be an excellent diagnostic tool for
      preoperative evaluation of the ALN status. To obviate the step of sentinel lymph
      node biopsy for determining the ALN status, combined evaluation of ALNs by these
      modalities may be more complementary than the use of a single modality.

PMID- 24866609
TI  - Development of a logistic regression formula for evaluation of subcentimeter
      thyroid nodules.
AB  - OBJECTIVES: The purpose of this study was to build a logistic regression formula
      for ameliorating the diagnosis of subcentimeter thyroid nodules. METHODS: The
      sonographic features of 889 subcentimeter nodules were reviewed retrospectively
      with reference of histologic results. The diagnostic performance of each feature
      was evaluated. Multivariate binary logistic regression was used to develop the
      formula for evaluation of subcentimeter nodules, and the cutoff value was decided
      for recommending biopsy. RESULTS: The logistic regression formula was -0.029age -
      2.063US1 - 0.812US2 + 1.781US3 + 1.627height-to-width ratio - 0.333 (for
      nonhypoechogenicity, US1 = 1; for hypoechogenicity, US1 = 0; for a well
      circumscribed margin, US2 = 1 and US3 = 0; for a microlobulated margin, US2 = 0
      and US3 = 1; and for an irregular margin, US2 = 0 and US3 = 0). The area under
      the receiver operating characteristic curve for the formula was 0.860. The
      sensitivity, specificity, positive predictive value, negative predictive value,
      and accuracy of the formula under the cutoff value of 0.284 were 90.9%, 54.0%,
      66.4%, 85.6%, and 72.5%, respectively. With the use of the formula, 229 of 830
      nodules could avoid surgery. CONCLUSIONS: A logistic regression formula with a
      cutoff value could provide an objective and easy tool with effective diagnostic
      performance, which could improve diagnosis of subcentimeter thyroid nodules and
      reduce unnecessary biopsy, decreasing costs and patient discomfort.

PMID- 24866610
TI  - Acoustic radiation force impulse imaging for evaluation of the thyroid gland.
AB  - OBJECTIVES: To study acoustic radiation force impulse (ARFI) imaging as a new
      quantitative and noninvasive tool for evaluating thyroid nodules and to compare
      ARFI imaging with other tools for studying thyroid nodules: sonography, real-time
      elastography, and fine-needle aspiration biopsy. METHODS: We conducted a
      prospective study from June 2011 to June 2012, which analyzed 157 thyroid nodules
      (129 benign and 28 malignant) using the ARFI technique and a 9-MHz probe. Shear
      wave velocities (SWVs) were obtained while the patients held their breath to
      avoid respiratory movement artifacts. All nodules underwent conventional
      sonography and real-time elastography of the thyroid gland. All patients received
      either a cytologic examination using fine-needle aspiration biopsy or a
      histologic examination from thyroid surgery to verify the diagnosis (reference
      standard). RESULTS: The mean SWV +/- SD on ARFI imaging in healthy, nodule-free
      thyroid glands was 2.04 +/- 0.51 m/s (range, 0.76-3.63 m/s). The mean SWV in
      benign thyroid nodules was 1.70 +/- 0.55 m/s (range, 0.50-2.80 m/s), and the mean
      SWV in malignant nodules was 3.39 +/- 1.15 m/s (range, 1.50-6.08 m/s). When we
      used an SWV greater than 2.50 m/s for the diagnosis of malignant nodules and less
      than 2.50 m/s for the diagnosis of benign nodules, the sensitivity and
      specificity of ARFI imaging were 85.7% and 96.0%, respectively. CONCLUSIONS: We
      found that SWVs were substantially higher in malignant nodules than benign ones.
      Perhaps if ARFI imaging is used in conjunction with sonographic findings and
      patient demographics, it will be possible to find a combination of factors that
      would yield a negative predictive value high enough to distinguish benign from
      malignant nodules with confidence, which may lead to a decrease in the biopsy
      rate for benign nodules.

PMID- 24866611
TI  - Radial collateral ligament of the elbow: sonographic characterization with
      cadaveric dissection correlation and magnetic resonance arthrography.
AB  - OBJECTIVES: An abnormality of the radial collateral ligament (RCL) in the setting
      of lateral epicondylitis can indicate a poor clinical outcome; therefore,
      accurate assessment is important. The purpose of this study was to characterize
      the proximal RCL attachment, or footprint, as seen on sonography using cadaveric
      dissection correlation and magnetic resonance arthrography. METHODS: For the
      first part of this study, 4 cadaveric elbow specimens were imaged with sonography
      before and after dissection to characterize the RCL. After Institutional Review
      Board approval with consent waived, 26 consecutive magnetic resonance (MR)
      arthrograms of the elbow were identified. The sonograms and MR arthrograms were
      retrospectively reviewed to measure the length of the RCL footprint and its
      percentage of the combined RCL and common extensor tendon (CET) humeral
      footprints. RESULTS: The mean RCL footprint length and percentage of the combined
      RCL and CET footprints were 8.4 mm (range, 7.4-10.0 mm) and 54% as measured from
      the elbow specimen sonograms and 9.1 mm (range, 6.4-12.5 mm) and 54% as measured
      from the MR arthrograms. The mean RCL footprint length combining data from
      specimens and MR arthrograms was 8.9 mm (range, 6.4-12.5 mm), covering 54% of the
      combined RCL and CET footprints. CONCLUSIONS: The RCL can be differentiated from
      the CET on sonography with knowledge of the RCL humeral footprint extent, which
      measured 8.9 mm in length and comprised 54% of the combined RCL and CET
      footprints.

PMID- 24866612
TI  - Reliability of B-mode sonography of the abdominal muscles in healthy adolescents
      in different body positions.
AB  - OBJECTIVES: The primary aim of this study was to determine the reliability of
      abdominal sonographic measurements in adolescents. The secondary aim was to
      determine whether age, sex, or body position had an impact on the reliability of
      abdominal muscle sonographic measurements in adolescents. METHODS: Sixty-nine
      asymptomatic participants aged 10 to 15 years without any postural faults
      participated in the study. The participants were divided into 3 age groups: 10 to
      11, 12 to 13, and 14 to 15 years, according to their sex. All participants
      underwent 3 measurements of the thickness of the transversus abdominis, internal
      oblique, and external oblique muscles on both sides of the body in the supine,
      sitting, and standing positions. The participants' measurements were taken at the
      end of normal exhalation, and the values were recorded in millimeters. RESULTS:
      Regardless of the participant's age, sex, and body position, the results for the
      3 measurements (intraclass correlation coefficient [ICC(3,3)]) for the
      transversus abdominis and internal oblique ranged from 0.81 to 0.99. With
      reference to the external oblique, intraexaminer reliability (ICC(3,3)) in the
      supine position ranged from 0.81 to 0.98, whereas in the sitting and standing
      positions, it fluctuated from 0.63 to 0.96. CONCLUSIONS: Sonography for
      assessment of the internal oblique and transversus abdominis muscles in different
      body positions in healthy adolescents aged 10 to 15 years was found to have
      reliability. To obtain high measurement reliability for the transversus abdominis
      and internal oblique at rest, at least 2 measurements should be performed,
      regardless of age, sex, or resting body position. Performing 3 measurements of
      the external oblique guarantees satisfactory reliability only in the supine
      position.

PMID- 24866613
TI  - A randomized clinical trial comparing the effectiveness of ultrasound guidance
      versus nerve stimulation for lateral popliteal-sciatic nerve blocks in obese
      patients.
AB  - OBJECTIVES: Ultrasound guidance may decrease the procedural time for many
      peripheral nerve blocks compared to nerve stimulation, but these studies have
      generally excluded obese patients. This single-blinded randomized clinical trial
      was designed to compare procedural times and related outcomes for ultrasound-
      versus nerve stimulation-guided lateral popliteal-sciatic nerve blockade
      specifically in obese patients. METHODS: With Institutional Review Board approval
      and informed consent, patients with a body mass index greater than 30 kg/m(2) who
      were scheduled for foot/ankle surgery and desiring a peripheral nerve block were
      offered enrollment. Study patients were randomly assigned to receive a lateral
      popliteal-sciatic nerve block under either ultrasound or nerve stimulation
      guidance. The patient and assessor were blinded to group assignment. The primary
      outcome was procedural time in seconds. Secondary outcomes included number of
      needle redirections, procedure-related pain, patient satisfaction with the block,
      success rate, sensory and motor onset times, block duration, and complication
      rates. RESULTS: Twenty-four patients were enrolled and completed the study. All
      patients had successful nerve blocks. The mean procedural times (SD) were 577
      (57) seconds under nerve stimulation and 206 (40) seconds with ultrasound
      guidance (P< .001; 95% confidence interval for difference, 329-412 seconds).
      Patients in the ultrasound group had fewer needle redirections and less procedure
      related pain, required less opioids, and were more satisfied with their block
      procedures. There were no statistically significant differences in other
      outcomes. CONCLUSIONS: The results of this study show that, for obese patients
      undergoing lateral popliteal-sciatic nerve blocks, ultrasound guidance reduces
      the procedural time and procedure-related pain and increases patient satisfaction
      compared to nerve stimulation while providing similar block characteristics.

PMID- 24866614
TI  - Reference charts for fetal corpus callosum length: a prospective cross-sectional
      study of 2950 fetuses.
AB  - OBJECTIVES: The purpose of this study was to establish reference charts for fetal
      corpus callosum length in a convenience sample. METHODS: A prospective cross
      sectional study was conducted at the Artemisia Fetal-Maternal Medical Center
      between December 2008 and January 2012. Among 16,975 fetal biometric measurements
      between 19 weeks and 37 weeks 6 days' gestation, 3438 measurements of the corpus
      callosum (20.3%) were available. After excluding 488 measurements (14.2%), a
      total of 2950 fetuses (85.8%) were considered and analyzed only once. Parametric
      and nonparametric quantile regression models were used for the statistical
      analysis. To evaluate the robustness of the proposed reference charts with
      respect to various distributional assumptions on the sonographic measurements at
      hand, we compared the gestational age (GA)-specific reference curves produced by
      the statistical methods used. RESULTS: The mean corpus callosum length was 26.18
      mm (SD, 4.5 mm; 95% confidence interval, 26.01-26.34 mm). The linear regression
      equation expressing the length of the corpus callosum as a function of GA was
      length (mm) = -11.17 + 1.62 * GA. The correlation between the dimension and
      gestation was expressed by the coefficient r = 0.83. Normal mean lengths
      according the parametric and nonparametric methods were defined for each week of
      gestation. CONCLUSIONS: This work provides new quantile-based reference charts
      for corpus callosum length measurements that may be useful for diagnosis of
      congenital corpus callosum anomalies in fetal life.

PMID- 24866615
TI  - Collaborative study of 4-dimensional fetal echocardiography in the first
      trimester of pregnancy.
AB  - OBJECTIVES: Accumulating evidence supports a role for 2-dimensional fetal
      echocardiography in the first trimester of pregnancy for the identification of
      congenital heart defects. Our objective was to investigate the role of 4
      dimensional (4D) sonography in the identification of congenital heart defects
      between 11 and 15 weeks of pregnancy. METHODS: This study included 4 centers with
      expertise in first-trimester 4D fetal echocardiography. Fetuses with and without
      confirmed heart defects were evaluated between 11 and 15 weeks and their volume
      data sets were uploaded onto a centralized file transfer protocol server.
      RESULTS: Forty-eight volume data sets from fetuses with normal (n = 17) and
      abnormal (n = 16) hearts were evaluated. Overall, the median (range) accuracy,
      sensitivity, and specificity, as well as the positive and negative likelihood
      ratios, for the identification of fetuses with congenital heart defects were 79%
      (77%-83%), 90% (70%-96%), 59% (58%-93%), 2.35 (2.05-9.80), and 0.18 (0.08-0.32),
      respectively. CONCLUSIONS: (1) Four-dimensional fetal echocardiography can be
      performed in the first and early second trimesters of pregnancy; and (2) 4D
      volume data sets obtained from fetuses between 11 and 15 weeks can be remotely
      acquired and accurately interpreted by different centers.

PMID- 24866616
TI  - Fetal skeletal dysplasias: sonographic indices associated with adverse outcomes.
AB  - OBJECTIVES: To assess the utility of biometric indices and amniotic fluid volume
      in identifying fetuses with lethal skeletal dysplasia. METHODS: A review of
      pregnancies with sonographic diagnosis of skeletal dysplasia between January 1997
      and March 2012 from a single institution was conducted. Biometric indices and
      amniotic fluid volumes were reviewed from the initial targeted sonograms and all
      subsequent examinations. Outcomes were verified in all cases. Pregnancies that
      resulted in fetal or neonatal death were considered to have lethal dysplasia, and
      those with survival to hospital discharge were considered to have nonlethal
      dysplasia. RESULTS: Of 45 fetuses with suspected skeletal dysplasia, 27 (60%)
      survived to hospital discharge; 9 (20%) died in the immediate neonatal period; 2
      (4%) resulted in stillbirth; and in 7 cases (16%), pregnancy termination was
      elected. Those with lethal dysplasia were more likely to have hydramnios on
      initial detection than those who survived to hospital discharge (83% versus 27%;
      P < .01). Pregnancies complicated by lethal skeletal dysplasia had a
      significantly lower femur length-to-abdominal circumference ratio and were more
      likely to have a ratio below 0.16 than those with neonatal survival (91% versus
      11%; P < 0.01). The lowest femur length-to-abdominal circumference ratio and the
      proportion with a ratio below 0.16 at any point in gestation were significantly
      different between those with lethal and nonlethal dysplasia (P< .01). As fetal
      size increased with advancing gestation, the relationship of sonographic
      parameters (eg, femur length-to-abdominal circumference ratio) became more
      pronounced. There was no infant survival when hydramnios was encountered at any
      point during gestation in the setting of a femur length-to-abdominal
      circumference ratio below 0.16. CONCLUSIONS: In our series, a femur length-to
      abdominal circumference ratio below 0.16 in conjunction with hydramnios
      effectively identified fetuses with lethal skeletal dysplasia.

PMID- 24866617
TI  - Prenatal sonographic detection of thoracic embryonal rhabdomyosarcoma.

PMID- 24866618
TI  - Number of yolk sacs in the diagnosis of monoamnionicity.

PMID- 24866619
TI  - Prenatal sonographic diagnosis of retinal nonattachment.

PMID- 24866620
TI  - AIUM practice guideline for documentation of an ultrasound examination.

PMID- 24866621
TI  - AIUM practice guideline for the performance of neurosonography in neonates and
      infants.

PMID- 24866622
TI  - AIUM practice guideline for the performance of peripheral arterial ultrasound
      examinations using color and spectral doppler imaging.

PMID- 24866623
TI  - AIUM practice guideline for the performance of ultrasound of the female pelvis.

PMID- 24866624
TI  - Nut consumption for vascular health and cognitive function.
AB  - Nuts are rich in many nutrients that can benefit multiple cardiometabolic
      functions, including arterial compliance, blood pressure, inflammation,
      glucoregulation and endothelial vasodilatation. Impaired vasodilatation may
      contribute to impaired cognitive performance due to poor cerebral perfusion. The
      present narrative review examines associations between nut consumption, vascular
      health and cognitive function. It includes a systematic search which identified
      seventy-one epidemiological or intervention studies in which effects of chronic
      nut consumption on blood pressure, glucoregulation, endothelial vasodilator
      function, arterial compliance, inflammatory biomarkers and cognitive performance
      were evaluated. Weighted mean changes were estimated where data were available;
      they indicate that nut consumption reduces blood pressure and improves
      glucoregulation, endothelial vasodilator function and inflammation, whilst a
      limited number of studies suggest that nut consumption may also improve cognitive
      performance. Further clinical trials are warranted to explore relationships
      between nut consumption, endothelial function and cognitive function. 

PMID- 24866625
TI  - Proposed changes to the Code affect every nurse.
AB  - Have you had the chance yet to read and digest the Nursing and Midwifery
      Council's proposed new code of professional conduct? If not, prepare yourself for
      sweeping changes that could have a fundamental effect on nurses' and midwives'
      practice. 

PMID- 24866627
TI  - Employers warned they must support nurses to meet revalidation demands.
AB  - Nurses need enough time--and the backing of their employers--to fulfil new
      revalidation requirements, the RCN has warned.

PMID- 24866626
TI  - Australian staffing ratios have led to safer care and motivated nurses.
AB  - A senior nurse who fought for mandatory minimum nurse patient ratios in the
      Australian state of Victoria has said the government's decision not to do the
      same in England is dangerous. 

PMID- 24866628
TI  - #WeNurses forum founder asks NMC to rethink code.
AB  - A nurse who set up a Twitter forum has called on the NMC to delete part of a new
      clause on social media in its draft revised code of conduct. 

PMID- 24866629
TI  - Confront bad practice immediately, managers told.
AB  - Ward managers are not tackling poor performance when it arises because they
      wrongly believe they cannot act without a formal human resources action plan, a
      conference heard. 

PMID- 24866631
TI  - Draft code puts personal onus on nurses to ensure fundamental care.
AB  - Nurses could risk their registration if they fail to ensure a patient's most
      basic needs--including hydration, nutrition and hygiene--are met.

PMID- 24866633
TI  - Major study into Schwartz rounds.
AB  - Nurse academics will carry out a major study looking at the impact of monthly
      meetings where staff share their concerns about care that is lacking in
      compassion. 

PMID- 24866634
TI  - Carter: 'Worrying discrepancy between executives and staff'.
AB  - Almost three quarters of NHS nurses responding to a survey said concerns they
      might raise about how their organisations are run would not be dealt with
      properly by their employer, according to healthcare think tank the King's Fund. 

PMID- 24866635
TI  - 'Staff fear raising the alarm on FGM'.
AB  - Nurses can play a vital role in eradicating female genital mutilation--but some
      may be afraid to report it for fear of being seen as culturally insensitive, says
      a senior nurse academic.

PMID- 24866636
TI  - Pain relief strategies for patients with dementia in acute settings.
AB  - An observational checklist is helping nurses to assess pain in patients with
      dementia who struggle to speak. 

PMID- 24866638
TI  - Trust raises numeracy concern.
AB  - Nurses are being turned down for NHS jobs because of poor maths skills, a trust
      chief executive has warned. 

PMID- 24866639
TI  - Care home nurses are 'inadequately' trained.
AB  - Hundreds of nursing home staff in northern England are receiving additional
      training from the NHS in an attempt to drive up care standards. 

PMID- 24866640
TI  - The NHS needs you--call goes out to nurses who left the profession.
AB  - Thousands of lapsed registrants in the UK have a wealth of knowledge, and a
      skills shortage means employers are keen to have them back, writes Kat Keogh.

PMID- 24866646
TI  - Multiple myeloma.

PMID- 24866647
TI  - Acute teams respond to emergency cancer call.
AB  - Acutely ill cancer patients who present at A&E can receive inadequate care.
      Innovative acute oncology services are being introduced to fill gaps in emergency
      staff's knowledge and ensure rapid referral to appropriate care.

PMID- 24866648
TI  - Bringing attention to domestic abuse.
AB  - Nursing skills are vital to the roles of those working with victims of domestic
      abuse in Nottinghamshire. Specialist nurses at Nottingham University Hospitals
      NHS Trust are involved in referring patients on to further support services and
      training hospital staff to identify and respond to signs of abuse.

PMID- 24866657
TI  - The Eastern Region Public Health Observatory.
AB  - The Eastern Region Public Health Observatory (ERPHO) became part of Public Health
      England on April 1 2013. Its website provides population health data, analysis
      and interpretation to support healthcare professionals in commissioning,
      prioritising and improving health outcomes.

PMID- 24866661
TI  - Shape of Caring review is a chance to ingrain compassion into training.

PMID- 24866662
TI  - Why are Wales, Scotland and Northern Ireland cast adrift?

PMID- 24866663
TI  - Don't forget the training needs of residential care home staff.

PMID- 24866665
TI  - Time spent with patients can teach more than a textbook.

PMID- 24866666
TI  - Emeritus professor Abe Guz was a great friend to nursing.

PMID- 24866669
TI  - Strategies for enhancing the delivery of person-centred care.
AB  - The implementation of person-centred care is considered complex and hard to
      sustain in today's NHS. To provide a dignified and caring experience to all,
      equality in health should consider individuals or groups at risk of isolation, as
      well as those who may not wish to, or may not be able to, self-manage fully. This
      may include, for example, the very young, older people, under-represented groups,
      homeless people or unconscious patients. This article considers varying levels of
      intervention in health and illness to make health and social care services
      sustainable and accessible to all. 

PMID- 24866670
TI  - Endocrine system: part 2.
AB  - This article, the last in the life sciences series, is the second of two articles
      on the endocrine system. It discusses human growth hormone, the pancreas and
      adrenal glands. The relationships between hormones and their unique functions are
      also explored. It is important that nurses understand how the endocrine system
      works and its role in maintaining health to provide effective care to patients.
      Several disorders caused by human growth hormone or that affect the pancreas and
      adrenal glands are examined. 

PMID- 24866671
TI  - Searching and critiquing the research literature.
AB  - This article explores how to search and critique the research literature. This
      involves explaining how to generate a robust literature review question, search
      databases in the most effective manner and produce a robust analysis of the
      literature. The article also outlines how a novice literature reviewer might
      develop the skills required to undertake a critical analysis of the available
      evidence. In this manner, the reader is able to present a coherent debate on the
      state of the literature and how this might be used to construct a comprehensive
      rationale for why further research or analysis of clinical practice may be needed
      in relation to a particular topic of interest. 

PMID- 24866672
TI  - Ascites.
AB  - Ascites is the accumulation of fluid in the peritoneal cavity. It can be caused
      by liver disease, tuberculosis, peritoneal infection, pancreatic disease and
      malignancies. In the emergency assessment unit where I work, many patients are
      admitted with ascites, mainly as a result of chronic liver disease or malignancy.

PMID- 24866674
TI  - Staff are an employer's best asset.
AB  - Meaningful workforce engagement helps employers ensure patients receive the best
      care, says Stephanie Jones Berry.

PMID- 24866673
TI  - A safe pair of hands.
AB  - There are opportunities for nurses to add to the credibility of the MHRA, the
      body that regulates medical equipment and medicines in the UK, reports Erin Dean.

PMID- 24866676
TI  - For every problem, a solution.
AB  - Learning to problem solve effectively is one of the most valuable techniques
      nurses can learn. There are many models to choose from but it is important to
      select a process that works for you. 

PMID- 24866677
TI  - Student life. Building a mentor programme.
AB  - Social networking can enhance communication among peer mentors in nursing
      education, writes Shellie Jean Radford.

PMID- 24866678
TI  - HCA leading the way to change.
AB  - A hospital ward run by healthcare assistants? Some might be sceptical, but not
      patients at Headley Court Defence Medical Rehabilitation Centre in Surrey who are
      about to be discharged from the military into civvy street. For them, the HCA-led
      ward is a welcome change from the traditional medically intense nurse-led units. 

PMID- 24866681
TI  - Nurses should not feel threatened by HCA education.
AB  - Health Education England, private providers and NHS organisations are to devise
      new fast-track apprenticeship schemes to enable healthcare assistants to register
      as qualified nurses. 

PMID- 24866682
TI  - Happy to be of assistance.
AB  - The new patient support assistant role showed one ward how much they had been
      missing, says Jenny Knight.

PMID- 24866683
TI  - Help for assistant practitioner students.
AB  - Taking a two-year degree while working full-time can be daunting, warns Susan
      Webb.

PMID- 24866684
TI  - The competence gap.
AB  - A study of HCAs' skills shows in-house training may be inadequate, and should be
      a priority for employers.

PMID- 24866685
TI  - 'AP degree gave me a confidence boost'.

PMID- 24866686
TI  - Legal advice. Insurance is essential, says Robert Griffith.
AB  - Liability for carelessness is given legal expression in the law relating to
      negligence. A patient harmed by the carelessness of a healthcare assistant can
      take action for damages. 

PMID- 24866687
TI  - Measuring malnutrition.
AB  - Poor nutrition can hinder a patient's recovery. It is important to spot and
      monitor its signs, says Robin Lewis.

PMID- 24866690
TI  - Magnetoresponsive discoidal photonic crystals toward active color pigments.
AB  - Photonic microdisks with a multilayered structure are designed from photocurable
      suspensions by step-by-step photolithography. In each step of photolithography,
      either a colloidal photonic crystal or a magnetic-particle-laden layer is stacked
      over the windows of a photomask. Sequential photolithography enables the creation
      of multilayered photonic microdisks that have brilliant structural colors that
      can be switched by an external magnetic field. 

PMID- 24866689
TI  - The effect of weight loss on the cardiac structure and function after
      laparoscopic adjustable gastric banding surgery in morbidly obese individuals.
AB  - BACKGROUND: Herein, we investigate the anthropometric, biochemical and left
      ventricle (LV) geometry changes following the laparoscopic adjustable gastric
      banding (LAGB) operation in morbidly obese individuals. METHODS: Eighty-three
      morbidly obese participants (mean age, 46.1 +/- 11.5 years; 30.1 % men),
      scheduled for elective LAGB were examined before and 12 months after the surgery.
      LV geometry and diastolic function were investigated by 2-dimensional
      echocardiography, whereas laboratory tests assessed the glycaemic, serum lipid
      and inflammatory marker profiles. RESULTS: Twelve months after the operation,
      body mass index (BMI) decreased from 46.9 +/- 7.2 kg/m(2) to 40.1 +/- 8.2 kg/m(2)
      (p < 0.05), which was associated with the significant improvements in glycaemic
      control, inflammatory state, LV end-diastolic diameter (53.6 +/- 4.6 mm vs. 52.9
      +/- 4.1 mm, p < 0.05), LV mass (223.6 +/- 61.3 vs. 215.4 +/- 52.7 g, p < 0.05)
      and LV mass index (53.9 +/- 14.1 g/m(2.7) vs. 52.0 +/- 12.3 g/m(2.7), p < 0.05).
      However, no overall improvements in LV geometry or the prevalence of LV
      hypertrophy subtypes were recorded 12 months after the LAGB. The reduction in LV
      end-diastolic diameter (beta = 0.56, p = 0.0001) and BMI (beta = 0.26, p = 0.015)
      were both associated with diminished LV mass. Additionally, a statistically
      significant correlation between LV mass and changes in BMI (R = 0.29, p = 0.007),
      waist circumference (R = 0.32, p = 0.004), LV end-diastolic diameter (R = 0.63, p
      = 0.0001) and E-wave deceleration time (R = -0.24, p = 0.03) were observed within
      our study population. CONCLUSIONS: LV mass decreases 12 months after LAGB
      surgery, but no improvements in LV geometry and function occur. The regression of
      LV mass is better predicted by weight loss than by reduction in blood pressure or
      changes in metabolic parameters.

PMID- 24866692
TI  - A life-cycle approach to food and nutrition security in India.
AB  - India's poor performance on critical food and nutrition security indicators
      despite substantial economic prosperity has been widely documented. These
      failings not only hamper national progress, but also contribute significantly to
      the global undernourished population, particularly children. While the recently
      passed National Food Security Act 2013 adopts a life-cycle approach to expand
      coverage of subsidized food grains to the most vulnerable households and address
      food security, there remains much to be desired in the legislation. Access to
      adequate food for 1.24 billion people is a multifaceted problem requiring an
      interconnected set of policy measures to tackle the various factors affecting
      food and nutrition security in India. In the present opinion paper, we discuss a
      fivefold strategy that incorporates a life-cycle approach, spanning reproductive
      health, bolstering citizen participation in existing national programmes,
      empowering women, advancing agriculture and better monitoring the Public
      Distribution System in order to fill the gaps in both access and adequacy of food
      and nutrition.

PMID- 24866691
TI  - Blood lead concentration and thyroid function during pregnancy: results from the
      Yugoslavia Prospective Study of Environmental Lead Exposure.
AB  - BACKGROUND: Although maternal hypothyroidism increases the risk of adverse
      neonatal and obstetric outcomes as well as lower IQ in children, the
      environmental determinants of maternal thyroid dysfunction have yet to be fully
      explored. OBJECTIVES: We aimed to examine associations between mid-pregnancy
      blood lead (BPb) and concomitant measures of thyroid function among participants
      in the Yugoslavia Prospective Study of Environmental Lead Exposure. METHODS: As
      part of a population-based prospective study of two towns in Kosovo-one with high
      levels of environmental lead and one with low-women were recruited during the
      second trimester of pregnancy, at which time blood samples and questionnaire data
      were collected. We measured concentrations of BPb, free thyroxine (FT4), thyroid
      stimulating hormone (TSH), and thyroid peroxidase antibodies (TPOAb) in archived
      serum samples. RESULTS: Compared with women from the unexposed town, women from
      the exposed town had lower mean FT4 (0.91 +/- 0.17 vs. 1.03 +/- 0.16 ng/dL),
      higher mean TPOAb (15.45 +/- 33.08 vs. 5.12 +/- 6.38 IU/mL), and higher mean BPb
      (20.00 +/- 6.99 vs. 5.57 +/- 2.01 MUg/dL). No differences in TSH levels were
      found. After adjustment for potential confounders, for each natural log unit
      increase in BPb, FT4 decreased by 0.074 ng/dL (95% CI: -0.10, -0.046 ng/dL), and
      the odds ratio for testing positive to TPOAb was 2.41 (95% CI: 1.53, 3.82). We
      found no association between BPb and TSH. CONCLUSIONS: Prolonged lead exposure
      may contribute to maternal thyroid dysfunction by stimulating autoimmunity to the
      thyroid gland.

PMID- 24866696
TI  - Physicochemical characteristics and droplet impact dynamics of superhydrophobic
      carbon nanotube arrays.
AB  - The physicochemical and droplet impact dynamics of superhydrophobic carbon
      nanotube arrays are investigated. These superhydrophobic arrays are fabricated
      simply by exposing the as-grown carbon nanotube arrays to a vacuum annealing
      treatment at a moderate temperature. This treatment, which allows a significant
      removal of oxygen adsorbates, leads to a dramatic change in wettability of the
      arrays, from mildly hydrophobic to superhydrophobic. Such change in wettability
      is also accompanied by a substantial change in surface charge and electrochemical
      properties. Here, the droplet impact dynamics are characterized in terms of
      critical Weber number, coefficient of restitution, spreading factor, and contact
      time. Based on these characteristics, it is found that superhydrophobic carbon
      nanotube arrays are among the best water-repellent surfaces ever reported. The
      results presented herein may pave a way for the utilization of superhydrophobic
      carbon nanotube arrays in numerous industrial and practical applications,
      including inkjet printing, direct injection engines, steam turbines, and
      microelectronic fabrication. 

PMID- 24866698
TI  - Aptaligner: automated software for aligning pseudorandom DNA X-aptamers from next
      generation sequencing data.
AB  - Next-generation sequencing results from bead-based aptamer libraries have
      demonstrated that traditional DNA/RNA alignment software is insufficient. This is
      particularly true for X-aptamers containing specialty bases (W, X, Y, Z, ...)
      that are identified by special encoding. Thus, we sought an automated program
      that uses the inherent design scheme of bead-based X-aptamers to create a
      hypothetical reference library and Markov modeling techniques to provide improved
      alignments. Aptaligner provides this feature as well as length error and noise
      level cutoff features, is parallelized to run on multiple central processing
      units (cores), and sorts sequences from a single chip into projects and
      subprojects. 

PMID- 24866694
TI  - Information handling by the brain: proposal of a new "paradigm" involving the
      roamer type of volume transmission and the tunneling nanotube type of wiring
      transmission.
AB  - The current view on the organization of the central nervous system (CNS) is
      basically anchored to the paradigm describing the brain as formed by networks of
      neurons interconnected by synapses. Synaptic contacts are a fundamental
      characteristic for describing CNS operations, but increasing evidence accumulated
      in the last 30 years pointed to a refinement of this view. A possible overcoming
      of the classical "neuroscience paradigm" will be here outlined, based on the
      following hypotheses: (1) the basic morpho-functional unit in the brain is a
      compartment of tissue (functional module) where different resident cells (not
      only neurons) work as an integrated unit; (2) in these complex networks, a
      spectrum of intercellular communication processes is exploited, that can be
      classified according to a dichotomous criterion: wiring transmission (occurring
      through physically delimited channels) and volume transmission (exploiting
      diffusion in the extracellular space); (3) the connections between cells can
      themselves be described as a network, leading to an information processing
      occurring at different levels from cell network down to molecular level; (4)
      recent evidence of the existence of specialized structures (microvesicles and
      tunneling nanotubes) for intercellular exchange of materials, could allow a
      further type of polymorphism of the CNS networks based on at least transient
      changes in cell phenotype. When compared to the classical paradigm, the proposed
      scheme of cellular organization could allow a strong increase of the degrees of
      freedom available to the whole system and then of its plasticity. Furthermore,
      long range coordination and correlation can be more easily accommodated within
      this framework.

PMID- 24866695
TI  - Serotonergic transmission after spinal cord injury.
AB  - Changes in descending serotonergic innervation of spinal neural activity have
      been implicated in symptoms of paralysis, spasticity, sensory disturbances and
      pain following spinal cord injury (SCI). Serotonergic neurons possess an enhanced
      ability to regenerate or sprout after many types of injury, including SCI.
      Current research suggests that serotonine (5-HT) release within the ventral horn
      of the spinal cord plays a critical role in motor function, and activation of 5
      HT receptors mediates locomotor control. 5-HT originating from the brain stem
      inhibits sensory afferent transmission and associated spinal reflexes; by
      abolishing 5-HT innervation SCI leads to a disinhibition of sensory transmission.
      5-HT denervation supersensitivity is one of the key mechanisms underlying the
      increased motoneuron excitability that occurs after SCI, and this
      hyperexcitability has been demonstrated to underlie the pathogenesis of
      spasticity after SCI. Moreover, emerging evidence implicates serotonergic
      descending facilitatory pathways from the brainstem to the spinal cord in the
      maintenance of pathologic pain. There are functional relevant connections between
      the descending serotonergic system from the rostral ventromedial medulla in the
      brainstem, the 5-HT receptors in the spinal dorsal horn, and the descending pain
      facilitation after tissue and nerve injury. This narrative review focussed on the
      most important studies that have investigated the above-mentioned effects of
      impaired 5-HT-transmission in humans after SCI. We also briefly discussed the
      promising therapeutical approaches with serotonergic drugs, monoclonal antibodies
      and intraspinal cell transplantation. 

PMID- 24866700
TI  - Lipopeptides from Bacillus and Paenibacillus spp.: A Gold Mine of Antibiotic
      Candidates.
AB  - The emergence of multidrug-resistant bacteria has placed a strain on health care
      systems and highlighted the need for new classes of antibiotics. Bacterial
      lipopeptides are secondary metabolites, generally produced by nonribosomal
      peptide synthetases that often exhibit broad-spectrum antimicrobial activity.
      Only two new structural types of antibiotics have entered the market in the last
      40 years, linezolid and the bacterial lipopeptide daptomycin. A wide variety of
      bacteria produce lipopeptides, however Bacillus and Paenibacillus spp. in
      particular have yielded several potent antimicrobial lipopeptides. Many of the
      lipopeptides produced by these bacteria have been known for decades and represent
      a potential gold mine of antibiotic candidates. This list includes the
      polymyxins, octapeptins, polypeptins, iturins, surfactins, fengycins,
      fusaricidins, and tridecaptins, as well as some novel examples, including the
      kurstakins. These lipopeptides have a wide variety of activities, ranging from
      antibacterial and antifungal, to anticancer and antiviral. This review presents a
      reasonably comprehensive list of each class of lipopeptide and their known
      homologues. Emphasis has been placed on their antimicrobial activities, as well
      other potential applications for this interesting class of substances. 

PMID- 24866699
TI  - Characterization of human alphabetaTCR repertoire and discovery of D-D fusion in
      TCRbeta chains.
AB  - The characterization of the human T-cell receptor (TCR) repertoire has made
      remarkable progress, with most of the work focusing on the TCRbeta chains. Here,
      we analyzed the diversity and complexity of both the TCRalpha and TCRbeta
      repertoires of three healthy donors. We found that the diversity of the TCRalpha
      repertoire is higher than that of the TCRbeta repertoire, whereas the usages of
      the V and J genes tended to be preferential with similar TRAV and TRAJ patterns
      in all three donors. The V-J pairings, like the V and J gene usages, were
      slightly preferential. We also found that the TRDV1 gene rearranges with the
      majority of TRAJ genes, suggesting that TRDV1 is a shared TRAV/DV gene
      (TRAV42/DV1). Moreover, we uncovered the presence of tandem TRBD (TRB D gene)
      usage in ~2% of the productive human TCRbeta CDR3 sequences. 

PMID- 24866703
TI  - C-H activation of pyrazolyl ligands by Ru(II).
AB  - Previously, hydridotris(pyrazolyl)borate (Tp) Ru(II) alkyl and aryl complexes of
      the type TpRu(L)(NCMe)R (R = methyl or aryl; L = charge-neutral two-electron
      donating ligand) were demonstrated to activate aromatic C-H bonds. To determine
      the impact of replacing the anionic Tp ligand with charge-neutral
      poly(pyrazolyl)alkane ligands, [(C(pz)4)Ru(P(OCH2)3CEt)(NCMe)Me][BAr'4] (pz =
      pyrazolyl, BAr'4 = tetrakis[3,5-bis(trifluoromethyl)phenyl]borate) was prepared.
      Heating a C6D6 solution of [(C(pz)4)Ru(P(OCH2)3CEt)(NCMe)Me][BAr'4] with 1 equiv
      of NCMe resulted in C-H activation of the 5-position of a pyrazolyl ring to yield
      [(kappa(3)-(N,C(5),N)C(pz)4)Ru(P(OCH2)3CEt)(NCMe)2][BAr'4] and CH4.
      Intramolecular C-H activation of the 5-position of a pyrazolyl ring also occurred
      when (eta(6)-p-cymene)Ru(P(OCH2)3CEt)(Br)Ph was heated in the presence of C(pz)4
      to yield [(kappa(3)-N,C(5),N)C(pz)4]Ru(P(OCH2)3CEt)(NCMe)Br and C6H6. Density
      functional theory calculations revealed that the different reactivities of
      TpRu(P(OCH2)3CEt)(NCMe)R and [(C(pz)4)Ru(P(OCH2)3CEt)(NCMe)Me][BAr'4] result from
      the stronger binding of the Tp pyrazolyl rings to Ru(II) compared to that of
      C(pz)4. 

PMID- 24866701
TI  - Chemical-genetic attenuation of focal neocortical seizures.
AB  - Focal epilepsy is commonly pharmacoresistant, and resective surgery is often
      contraindicated by proximity to eloquent cortex. Many patients have no effective
      treatment options. Gene therapy allows cell-type specific inhibition of neuronal
      excitability, but on-demand seizure suppression has only been achieved with
      optogenetics, which requires invasive light delivery. Here we test a combined
      chemical-genetic approach to achieve localized suppression of neuronal
      excitability in a seizure focus, using viral expression of the modified
      muscarinic receptor hM4Di. hM4Di has no effect in the absence of its selective,
      normally inactive and orally bioavailable agonist clozapine-N-oxide (CNO).
      Systemic administration of CNO suppresses focal seizures evoked by two different
      chemoconvulsants, pilocarpine and picrotoxin. CNO also has a robust anti-seizure
      effect in a chronic model of focal neocortical epilepsy. Chemical-genetic seizure
      attenuation holds promise as a novel approach to treat intractable focal epilepsy
      while minimizing disruption of normal circuit function in untransduced brain
      regions or in the absence of the specific ligand. 

PMID- 24866704
TI  - Solid-state hierarchical cyclodextrin-based supramolecular polymer constructed by
      primary, secondary, and tertiary azido interactions.
AB  - The crystallization of a di-azido-alpha-cyclodextrin revealed a polymeric self
      assembly involving a variety of azido-type interactions. The crystal arrangement
      relies on the cooperativity of a primary azido inclusion, a secondary azido-azido
      interaction involving an unprecedented distribution of canonical forms, and a
      tertiary azido-groove interaction. The second azido group brings in a major
      contribution to the supramolecular structure illustrating the benefit of a
      difunctionalization for the generation of hierarchy. 

PMID- 24866693
TI  - Complex molecular regulation of tyrosine hydroxylase.
AB  - Tyrosine hydroxylase, the rate-limiting enzyme in catecholamine biosynthesis, is
      strictly controlled by several interrelated regulatory mechanisms. Enzyme
      synthesis is controlled by epigenetic factors, transcription factors, and mRNA
      levels. Enzyme activity is regulated by end-product feedback inhibition.
      Phosphorylation of the enzyme is catalyzed by several protein kinases and
      dephosphorylation is mediated by two protein phosphatases that establish a
      sensitive process for regulating enzyme activity on a minute-to-minute basis.
      Interactions between tyrosine hydroxylase and other proteins introduce additional
      layers to the already tightly controlled production of catecholamines. Tyrosine
      hydroxylase degradation by the ubiquitin-proteasome coupled pathway represents
      yet another mechanism of regulation. Here, we revisit the myriad mechanisms that
      regulate tyrosine hydroxylase expression and activity and highlight their
      physiological importance in the control of catecholamine biosynthesis. 

PMID- 24866707
TI  - Response to Early Intensive Behavioral Intervention for autism--an umbrella
      approach to issues critical to treatment individualization.
AB  - Integrating knowledge across the disciplines of genetics, neurological, and
      behavioral science targets, so far, early identification of children with autism
      and thus early access to intervention. Cross-discipline collaboration might be
      substantially improve treatment efficacy via individualized treatment based on
      the child and family needs, consistency across treatment providers and careful
      planning of skill curricula, setting and techniques. This paper documents the
      current state of five main issues critical to treatment individualization where
      cross-discipline collaboration is warranted: (1) developmental timing, (2)
      treatment intensity, (3) heterogeneity in treatment response, (4) program breath
      and flexibility, and (5) formats of treatment provision. 

PMID- 24866705
TI  - Copeptin levels remain unchanged during the menstrual cycle.
AB  - BACKGROUND: Copeptin, a surrogate marker for arginin vasopressin production, is
      evaluated as an osmo-dependent stress and inflammatory biomarker in different
      diseases. We investigated copeptin during the menstrual cycle and its
      relationship to sex hormones, markers of subclinical inflammation and estimates
      of body fluid. METHODS: In 15 healthy women with regular menstrual cycles, blood
      was drawn on fifteen defined days of their menstrual cycle and was assayed for
      copeptin, progesterone, estradiol, luteinizing hormone, high-sensitive C-reactive
      protein, tumor necrosis factor-alpha and procalcitonin. Symptoms of fluid
      retention were assessed on each visit, and bio impedance analysis was measured
      thrice to estimate body fluid changes. Mixed linear model analysis was performed
      to assess the changes of copeptin across the menstrual cycle and the relationship
      of sex hormones, markers of subclinical inflammation and estimates of body fluid
      with copeptin. RESULTS: Copeptin levels did not significantly change during the
      menstrual cycle (p = 0.16). Throughout the menstrual cycle, changes in estradiol
      (p = 0.002) and in the physical premenstrual symptom score (p = 0.01) were
      positively related to copeptin, but changes in other sex hormones, in markers of
      subclinical inflammation or in bio impedance analysis-estimated body fluid were
      not (all p = ns). CONCLUSION: Although changes in estradiol and the physical
      premenstrual symptom score appear to be related to copeptin changes, copeptin
      does not significantly change during the menstrual cycle.

PMID- 24866706
TI  - Perinatal alpha-linolenic acid availability alters the expression of genes
      related to memory and to epigenetic machinery, and the Mecp2 DNA methylation in
      the whole brain of mouse offspring.
AB  - Many animal and human studies indicated that dietary omega-3 fatty acids could
      have beneficial roles on brain development, memory, and learning. However, the
      exact mechanisms involved are far from being clearly understood, especially for
      alpha-linolenic acid (ALA), which is the precursor for the omega-3 elongation and
      desaturation pathways. This study investigated the alterations induced by
      different intakes of flaxseed oil (containing 50% ALA), during gestation and
      lactation, upon the expression of genes involved in neurogenesis, memory-related
      molecular processes, and DNA methylation, in the brains of mouse offspring at the
      end of lactation (postnatal day 19, P19). In addition, DNA methylation status for
      the same genes was investigated. Maternal flaxseed oil supplementation during
      lactation increased the expression of Mecp2, Ppp1cc, and Reelin, while decreasing
      the expression of Ppp1cb and Dnmt3a. Dnmt1 expression was decreased by postnatal
      flaxseed oil supplementation but this effect was offset by ALA deficiency during
      gestation. Mecp2 DNA methylation was decreased by maternal ALA deficiency during
      gestation, with a more robust effect in the lactation-deficient group. In
      addition, linear regression analysis revealed positive correlations between
      Mecp2, Reelin, and Ppp1cc, between Gadd45b, Bdnf, and Creb1, and between Egr1 and
      Dnmt1, respectively. However, there were no correlations, in any gene, between
      DNA methylation and gene expression. In summary, the interplay between ALA
      availability during gestation and lactation differentially altered the expression
      of genes involved in neurogenesis and memory, in the whole brain of the offspring
      at the end of lactation. The Mecp2 epigenetic status was correlated with ALA
      availability during gestation. However, the epigenetic status of the genes
      investigated was not associated with transcript levels, suggesting that either
      the regulation of these genes is not necessarily under epigenetic control, or
      that the whole brain model is not adequate for the exploration of epigenetic
      regulation in the context of this study. 

PMID- 24866708
TI  - Magnetic resonance imaging abnormalities in the resection region correlate with
      histopathological type, gliosis extent, and postoperative outcome in pediatric
      cortical dysplasia.
AB  - OBJECT.: The authors conducted a study to correlate histopathological features,
      MRI findings, and postsurgical outcomes in children with cortical dysplasia (CD)
      by performing a novel resection site-specific evaluation. METHODS: The study
      cohort comprised 43 children with intractable epilepsy and CD. The MR image
      review was blinded to pathology but with knowledge of the resection location. An
      MRI score (range 0-7) was calculated for each resection region based on the
      number of imaging features of CD and was classified as "lesional" or
      "nonlesional" according to all imaging features. Outcome was determined using the
      International League Against Epilepsy (ILAE) scale. The determination of
      pathological CD type was based on the ILAE 2011 consensus classification system,
      and the cortical gliosis pattern was assessed on GFAP staining. RESULTS: There
      were 89 resection regions (50 ILAE Type I, 29 Type IIa, and 10 Type IIb). Eleven
      (25.6%) of 43 children had more than one type of CD. The authors observed MRI
      abnormalities in 63% of patients, characteristic enough to direct resection
      (lesional) in 42%. Most MRI features, MRI score >= 3, and lesional abnormalities
      were more common in patients with Type II CD. Increased cortical signal was more
      common in those with Type IIb (70%) rather than Type IIa (17.2%) CD (p = 0.004).
      A good outcome was demonstrated in 39% of children with Type I CD and 72% of
      those with Type II CD (61% in Type IIa and 100% in Type IIb) (p = 0.03). A
      lesional MRI abnormality and an MRI score greater than 3 correlated with good
      outcome in 78% and 90% of patients, respectively (p < 0.03). Diffuse cortical
      gliosis was more prevalent in Type II CD and in resection regions exhibiting MRI
      abnormalities. Complete surgical exclusion of the MRI abnormality was associated
      with a better postoperative outcome. CONCLUSIONS: This study provides a detailed
      correlation of MRI findings, neuropathological features, and outcomes in children
      with intractable epilepsy by using a novel resection site-specific evaluation.
      Because 25% of the patients had multiple CD subtypes, a regional analysis
      approach was mandated. Those children with lesional MRI abnormalities, Type II
      CD, and surgical exclusion of the MRI abnormality had better outcomes. Type II CD
      is more detectable by MRI than other types, partly because of the greater extent
      of associated gliosis in Type II. Although MRI findings were correlated with the
      pathological CD type and outcome in this study, the majority of patients (58%)
      did not have MRI findings that could direct surgical therapy, underscoring the
      need for improved MRI techniques for detection and for the continued use of
      multimodal evaluation methods in patient selection.

PMID- 24866709
TI  - Differentiation and quantification of synthetic phosphatidylethanol (PEth)
      homologues by 1H- and 13C-NMR in polar organic solvents.
AB  - Various phosphatidylethanol (PEth) derivatives, the corresponding reversed
      positional isomers (RPI-PEths), lyso-PEth-16:0, and penta-deuterium-labeled PEth
      analogs (d5-PEths), were synthesized by enzyme-independent synthetic routes. A
      general solvent system consisting of a mixture of acetone-d6 and methanol-d4
      (97:3; v/v) was found to provide a good solubilizing capacity and excellent
      hydrogen-1 NMR ((1)H-NMR) peak resolution of various PEth homologues. Analytical
      differentiation of PEth from the corresponding RPI-PEth by carbon-13 NMR ((13)C
      NMR) was demonstrated by comparison of the (13)C-NMR signals of the carbonyl
      groups, the allylic positions, and of the beta-carbons. An exemplary stable long
      term room temperature, DMSO-d6-based, and proton-sensitive quantitative nuclear
      magnetic resonance ((1)H-qNMR) independently quantified calibrator comprising
      PEth-16:0/18:1 for liquid chromatography (tandem) mass spectrometry (LC-MS/MS)
      analytical applications were prepared by employment of sodium dodecyl sulfate
      (SDS) as a solubilizing additive. In summary, novel hypothetically occurring PEth
      derivatives, e.g., RPI-PEths, have been independently synthesized with regio- and
      stereochemical control. Use of polar organic solvents, e.g., mixtures of acetone
      d6 and methanol-d4 or DMSO-d6, improves spectral line shapes as compared to
      traditional hydrophobic solvents and allow for analytical differentiation between
      closely related PEth derivatives, as well as LC-MS/MS-independent concentration
      determination of dissolved single species by employment of (1)H-qNMR. 

PMID- 24866710
TI  - Metabolic fingerprinting based on high-resolution tandem mass spectrometry: a
      reliable tool for wine authentication?
AB  - Ultra-high-performance liquid chromatography coupled with quadrupole time-of
      flight mass spectrometry (MS) and an alternative technology represented by direct
      analysis in real time coupled with quadrupole time-of-flight MS were investigated
      for metabolic fingerprinting of 343 red and white wine samples. Direct injection
      of pure wine and an extraction procedure optimized for isolation of polyphenols
      were used to compare different analytical and data handling strategies. After
      data processing and data pretreatment, principal component analysis was initially
      used to explore the data structure. Initially, the unsupervised models revealed a
      notable clustering according to the grape varieties, and therefore supervised
      orthogonal partial least squares discriminant analysis models were created and
      validated for separation of red and white wines according to the grape variety.
      The validated orthogonal partial least squares discriminant analysis models based
      on data (ions) recorded in positive ionization mode were able to classify
      correctly 95% of samples. In parallel, authentication parameters, such as origin
      and vintage, were evaluated, and they are discussed. A tentative identification
      of markers was performed using accurate mass measurement of MS and MS/MS spectra,
      different software packages and different online libraries. In this way,
      different flavonol glucosides and polyphenols were identified as wine markers
      according to the grape varieties.

PMID- 24866711
TI  - Teaching analytical chemistry in China: past, present, and future perspectives.

PMID- 24866712
TI  - Zoom-TOFMS: addition of a constant-momentum-acceleration "zoom" mode to time-of
      flight mass spectrometry.
AB  - In this study, we demonstrate the performance of a new mass spectrometry concept
      called zoom time-of-flight mass spectrometry (zoom-TOFMS). In our zoom-TOFMS
      instrument, we combine two complementary types of TOFMS: conventional, constant
      energy acceleration (CEA) TOFMS and constant-momentum acceleration (CMA) TOFMS to
      provide complete mass-spectral coverage as well as enhanced resolution and duty
      factor for a narrow, targeted mass region, respectively. Alternation between CEA-
      and CMA-TOFMS requires only that electrostatic instrument settings (i.e.,
      reflectron and ion optics) and ion acceleration conditions be changed. The
      prototype zoom-TOFMS instrument has orthogonal-acceleration geometry, a total
      field-free distance of 43 cm, and a direct-current glow-discharge ionization
      source. Experimental results demonstrate that the CMA-TOFMS "zoom" mode offers
      resolution enhancement of 1.6 times over single-stage acceleration CEA-TOFMS. For
      the atomic mass range studied here, the maximum resolving power at full-width
      half-maximum observed for CEA-TOFMS was 1,610 and for CMA-TOFMS the maximum was
      2,550. No difference in signal-to-noise (S/N) ratio was observed between the
      operating modes of zoom-TOFMS when both were operated at equivalent repetition
      rates. For a 10-kHz repetition rate, S/N values for CEA-TOFMS varied from 45 to
      990 and from 67 to 10,000 for CMA-TOFMS. This resolution improvement is the
      result of a linear TOF-to-mass scale and the energy-focusing capability of CMA
      TOFMS. Use of CMA also allows ions outside a given m/z range to be rejected by
      simple ion-energy barriers to provide a substantial improvement in duty factor. 

PMID- 24866713
TI  - Establishing analytical comparability for "biosimilars": filgrastim as a case
      study.
AB  - Biosimilars are defined as biotherapeutic drugs that have been shown to have
      comparable quality, safety, and efficacy to the original product. Fuelled by the
      patent cliff in the next 5 years, the focus of the biopharmaceutical industry is
      gradually shifting towards production of biosimilars. Scientific and regulatory
      issues around development and approval of these biosimilars have been a topic of
      great interest and debate recently. Unlike the conventional small molecular
      weight drugs, biosimilars exhibit high complexity at the molecular level. Slight
      variations during the manufacturing of these complex protein molecules may lead
      to the significant changes in the safety and efficacy profile of the therapeutic
      product. Establishing comparability to the reference product is essential for
      successful approval of a biosimilar product. Analytical comparability provides
      the foundation to this exercise. This paper presents data from such an exercise
      involving use of several orthogonal analytical tools for establishing analytical
      comparability. Granulocyte colony-stimulating factor (GCSF/Filgrastim) expressed
      in Escherichia coli has been selected as the model protein. The approach would be
      of interest to those engaged in development and commercialization of biosimilars.

PMID- 24866714
TI  - Affinity selection-based two-dimensional chromatography coupled with high
      performance liquid chromatography-mass spectrometry for discovering xanthine
      oxidase inhibitors from Radix Salviae Miltiorrhizae.
AB  - Xanthine oxidase (XOD) is a key oxidative enzyme to the pathogenesis of
      hyperuricemia and certain diseases induced by excessive reactive oxygen species.
      XOD inhibitors could provide an important therapeutic approach to treat such
      diseases. A new method using affinity selection-based two-dimensional
      chromatography coupled with liquid chromatography-mass spectrometry was developed
      for the online screening of potential XOD inhibitors from Radix Salviae
      Miltiorrhizae. Based on our previous study, the two-dimensional, turbulent-flow
      chromatography (TFC) was changed to a mixed-mode anion-exchange/reversed-phase
      column and one reversed-phase column. The developed method was validated to be
      selective and sensitive for screening XOD-binding compounds, especially weak
      acidic ones, in the extracts. Three salvianolic acids were screened from the
      Radix Salviae Miltiorrhizae extract via the developed method. The XOD inhibitory
      activities of salvianolic acid C and salvianolic acid A were confirmed, and their
      inhibitory modes were measured. Salvianolic acid C exhibited potent XOD
      inhibitory activity with an IC(50) of 9.07 MUM. This work demonstrated that the
      developed online, two-dimensional TFC/LC-MS method was effective in discovering
      the binding affinity of new compounds from natural extracts for target proteins,
      even at low concentrations.

PMID- 24866717
TI  - Organic nanospheres with an internal bicontinuous structure and their responsive
      phase inversion.
AB  - Nanospheres with an internal bicontinuous structure were obtained through
      hierarchical self-assembly of a dendritic block terpolymer in selective solvents.
      The self-assembly underwent a unique three stage process involving unimolecular
      micelle formation, multimicelle aggregation and microphase separation within a
      self-confined space. Reversible phase inversion of the nanospheres in response to
      the solvent environment was observed. 

PMID- 24866716
TI  - Hollow and concave nanoparticles via preferential oxidation of the core in
      colloidal core/shell nanocrystals.
AB  - Hollow and concave nanocrystals find applications in many fields, and their
      fabrication can follow different possible mechanisms. We report a new route to
      these nanostructures that exploits the oxidation of Cu(2-x)Se/Cu(2-x)S core/shell
      nanocrystals with various etchants. Even though the Cu(2-x)Se core is encased in
      a thick Cu(2-x)S shell, the initial effect of oxidation is the creation of a void
      in the core. This is rationalized in terms of diffusion of Cu(+) ions and
      electrons from the core to the shell (and from there to the solution).
      Differently from the classical Kirkendall effect, which entails an imbalance
      between in-diffusion and out-diffusion of two different species across an
      interface, the present mechanism can be considered as a limiting case of such
      effect and is triggered by the stronger tendency of Cu(2-x)Se over Cu(2-x)S
      toward oxidation and by fast Cu(+) diffusion in copper chalcogenides. As the
      oxidation progresses, expansion of the inner void erodes the entire Cu(2-x)Se
      core, accompanied by etching and partial collapse of the shell, yielding Cu(2
      x)S(y)Se(1-y) concave particles.

PMID- 24866715
TI  - Improving the quality of adult mortality data collected in demographic surveys:
      validation study of a new siblings' survival questionnaire in Niakhar, Senegal.
AB  - BACKGROUND: In countries with limited vital registration, adult mortality is
      frequently estimated using siblings' survival histories (SSHs) collected during
      Demographic and Health Surveys (DHS). These data are affected by reporting
      errors. We developed a new SSH questionnaire, the siblings' survival calendar
      (SSC). It incorporates supplementary interviewing techniques to limit omissions
      of siblings and uses an event history calendar to improve reports of dates and
      ages. We hypothesized that the SSC would improve the quality of adult mortality
      data. METHODS AND FINDINGS: We conducted a retrospective validation study among
      the population of the Niakhar Health and Demographic Surveillance System in
      Senegal. We randomly assigned men and women aged 15-59 y to an interview with
      either the DHS questionnaire or the SSC. We compared SSHs collected in each group
      to prospective data on adult mortality collected in Niakhar. The SSC reduced
      respondents' tendency to round reports of dates and ages to the nearest multiple
      of five or ten ("heaping"). The SSC also had higher sensitivity in recording
      adult female deaths: among respondents whose sister(s) had died at an adult age
      in the past 15 y, 89.6% reported an adult female death during SSC interviews
      versus 75.6% in DHS interviews (p = 0.027). The specificity of the SSC was
      similar to that of the DHS questionnaire, i.e., it did not increase the number of
      false reports of deaths. However, the SSC did not improve the reporting of adult
      deaths among the brothers of respondents. Study limitations include sample
      selectivity, limited external validity, and multiple testing. CONCLUSIONS: The
      SSC has the potential to collect more accurate SSHs than the questionnaire used
      in DHS. Further research is needed to assess the effects of the SSC on estimates
      of adult mortality rates. Additional validation studies should be conducted in
      different social and epidemiological settings. TRIAL REGISTRATION: Controlled
      Trials.com ISRCTN06849961

PMID- 24866719
TI  - Comparison of burn size after retinal photocoagulation by conventional and high
      power short-duration methods.

PMID- 24866718
TI  - Knockdown of mitogen-activated protein kinase (MAPK) signalling in the midgut of
      Anopheles stephensi mosquitoes using antisense morpholinos.
AB  - Arthropod-borne infectious diseases are responsible for nearly 1.5 million deaths
      annually across the globe, with malaria responsible for >50% of these deaths.
      Recent efforts to enhance malaria control have focused on developing genetically
      modified Anopheles mosquitoes that are resistant to malaria parasite infection by
      manipulating proteins that are essential to the immune response. Although this
      approach has shown promise, the lack of efficient genetic tools in the mosquito
      makes it difficult to investigate innate immunity using reverse genetics. Current
      gene knockdown strategies based on small interfering RNA are typically
      labourious, inefficient, and require extensive training. In the present study, we
      describe the use of morpholino antisense oligomers to knockdown MEK-ERK
      signalling in the midgut of Anopheles stephensi through a simple feeding
      protocol. Anti-MEK morpholino provided in a saline meal was readily ingested by
      female mosquitoes with minimal toxicity and resulted in knockdown of total MEK
      protein levels 3-4 days after morpholino feeding. Further, anti-MEK morpholino
      feeding attenuated inducible phosphorylation of the downstream kinase ERK and, as
      predicted by previous work, reduced parasite burden in mosquitoes infected with
      Plasmodium falciparum. To our knowledge, this is the first example of morpholino
      use for target protein knockdown via feeding in an insect vector. Our results
      suggest this method is not only efficient for studies of individual proteins, but
      also for studies of phenotypic control by complex cell signalling networks. As
      such, our protocol is an effective alternative to current methods for gene
      knockdown in arthropods.

PMID- 24866720
TI  - Aberrant promoter DNA methylation inhibits bone morphogenetic protein 2
      expression and contributes to drug resistance in breast cancer.
AB  - Bone morphogenetic protein 2 (BMP2) is a growth factor that is involved in the
      development and progression of various types of cancer. However, the epigenetic
      regulation of the expression of BMP2 and the association between BMP2 expression
      and drug resistance in breast cancer remains to be elucidated. The present study
      reported that the expression of BMP2 was significantly decreased in primary
      breast cancer samples and the MCF-7/ADR breast cancer mulitdrug resistance cell
      line, which was closely associated with its promoter DNA methylation status. The
      expression of BMP2 in MCF-7/ADR cells markedly increased when treated with 5-Aza
      2'-deoxycytidine. Knockdown of BMP2 by specific small interfering RNA enhanced
      the chemoresistance of the MCF-7 breast cancer cell line. These findings
      indicated that epigenetic silencing of BMP2 in breast cancer may be involved in
      breast cancer progression and drug resistance, and provided a novel prognostic
      marker and therapeutic strategy for breast cancer. 

PMID- 24866721
TI  - Alteration of glycine receptor immunoreactivity in the auditory brainstem of mice
      following three months of exposure to radiofrequency radiation at SAR 4.0 W/kg.
AB  - The increasing use of mobile communication has triggered an interest in its
      possible effects on the regulation of neurotransmitter signals. Due to the close
      proximity of mobile phones to hearing-related brain regions during usage, its use
      may lead to a decrease in the ability to segregate sounds, leading to serious
      auditory dysfunction caused by the prolonged exposure to radiofrequency (RF)
      radiation. The interplay among auditory processing, excitation and inhibitory
      molecule interactions plays a major role in auditory function. In particular,
      inhibitory molecules, such a glycine, are predominantly localized in the auditory
      brainstem. However, the effects of exposure to RF radiation on auditory function
      have not been reported to date. Thus, the aim of the present study was to
      investigate the effects of exposure to RF radiation on glycine receptor (GlyR)
      immunoreactivity (IR) in the auditory brainstem region at 835 MHz with a specific
      absorption rate of 4.0 W/kg for three months using free-floating
      immunohistochemistry. Compared with the sham control (SC) group, a significant
      loss of staining intensity of neuropils and cells in the different subdivisions
      of the auditory brainstem regions was observed in the mice exposed to RF
      radiation (E4 group). A decrease in the number of GlyR immunoreactive cells was
      also noted in the cochlear nuclear complex [anteroventral cochlear nucleus
      (AVCN), 31.09%; dorsal cochlear nucleus (DCN), 14.08%; posteroventral cochlear
      nucleus (PVCN), 32.79%] and the superior olivary complex (SOC) [lateral superior
      olivary nucleus (LSO), 36.85%; superior paraolivary nucleus (SPN), 24.33%, medial
      superior olivary nucleus (MSO), 23.23%; medial nucleus of the trapezoid body
      (MNTB), 10.15%] of the mice in the E4 group. Auditory brainstem response (ABR)
      analysis also revealed a significant threshold elevation of in the exposed (E4)
      group, which may be associated with auditory dysfunction. The present study
      suggests that the auditory brainstem region is susceptible to chronic exposure to
      RF radiation, which may affect the function of the central auditory system.

PMID- 24866722
TI  - Effect of active Notch signaling system on the early repair of rat sciatic nerve
      injury.
AB  - It is all known that dedifferentiated Schwann cells (SCs) play an important role
      in neural regeneration, and Notch signaling has complex and extensive regulatory
      functions in dedifferentiated SCs. So studies have focused on how to improve
      peripheral nerve repair by regulating proliferation and dedifferentiation in SCs
      with Notch signaling meloculars.We have found SCs can be activated when adding
      Recombinant rat jagged1/FC chimera (an activator of the Notch signaling system)
      in vivo. Compared with that of the control groups, at 4 weeks post-surgery nerve
      regeneration and functional rehabilitation in the Recombinant rat jagged1/FC
      chimera group were advanced significantly, and the expression of neurotrophic
      factors in the regenerated nerves was elevated largely. These results indicated
      that SCs activated by Notch signaling could promote nerve repair effectively in
      the early regenerative stage, suggesting the possible clinical application for
      the treatment of peripheral nerve defects. 

PMID- 24866723
TI  - Hemoglobin-based oxygen carrier attenuates cerebral damage by improving tissue
      oxygen preload in a dog model of cardiopulmonary bypass.
AB  - In order to investigate whether hemoglobin-based oxygen carrier (HBOC) attenuates
      cardiopulmonary bypass (CPB)-induced cerebral damage. Male adult Beagle dogs were
      randomly divided into sham, control, and HBOC groups. After establishment of CPB
      model, hearts were arrested for 2 h and reperfused for 2 h. HBOC improved
      intracerebral O2 tensions and reduced the releases of biomarkers for cerebral
      damage, including neuron-specific enolase and S100beta in both cerebrospinal
      fluid and serum. Moreover, HBOC attenuated the releases of tumor necrosis factor
      alpha and interleukin-1beta after CPB. Therefore, our findings suggest that HBOC
      could reduce cerebral damage after CPB, which was probably associated with
      improvement of tissue O2 preload. 

PMID- 24866724
TI  - Effect of size on biological properties of nanoparticles employed in gene
      delivery.
AB  - CONTEXT: The size of nanoparticles plays a pivotal role in determining the gene
      delivery efficiency. OBJECTIVE: A focus on the studies done to investigate the
      effect of nanoparticles size on biological aspects of gene delivery. METHODS: A
      through literature survey has been done regarding studies done to investigate the
      effect of nanoparticles size on uptake, transfection efficiency and
      biodistribution has been cited in the present review. RESULTS AND CONCLUSION: The
      gene delivery efficacy may depend on conjugation of several factors such as the
      chemical structure of polymers, cell type, and nanoparticle size, composition and
      interaction with cells.

PMID- 24866725
TI  - Nanostructured lipid carriers as a potential vehicle for Carvedilol delivery:
      Application of factorial design approach.
AB  - Present invention relates to design of nanostructured lipid carriers (NLC) to
      augment oral bioavailability of Carvedilol (CAR). In this attempt, formulations
      of CAR-NLCs were prepared with glyceryl-monostearate (GMS) as a lipid, poloxamer
      188 as a surfactant and tween 80 as a co-surfactant using high pressure
      homogenizer by 2(3) factorial design approach. Formed CAR-NLCs were assessed for
      various performance parameters. Accelerated stability studies demonstrated
      negligible change in particle size and entrapment efficiency, after storage at
      specified time up to 3 months. The promising findings in this investigation
      suggest the practicability of these systems for enhancement of bioavailability of
      drugs like CAR. 

PMID- 24866726
TI  - College students with Internet addiction decrease fewer Behavior Inhibition Scale
      and Behavior Approach Scale when getting online.
AB  - INTRODUCTION: The aim of the study is to compare the reinforcement sensitivity
      between online and offline interaction. The effect of gender, Internet addiction,
      depression, and online gaming on the difference of reinforcement sensitivity
      between online and offline were also evaluated. METHODS: The subjects were 2,258
      college students (1,066 men and 1,192 women). They completed the Behavior
      Inhibition Scale and Behavior Approach Scale (BIS/BAS) according to their
      experience online or offline. Internet addiction, depression, and Internet
      activity type were evaluated simultaneously. RESULTS: The results showed that
      reinforcement sensitivity was lower when interacting online than when interacting
      offline. College students with Internet addiction decrease fewer score on BIS and
      BAS after getting online than did others. The higher reward and aversion
      sensitivity are associated with the risk of Internet addiction. DISCUSSION: The
      fun seeking online might contribute to the maintenance of Internet addiction.
      This suggests that reinforcement sensitivity would change after getting online
      and would contribute to the risk and maintenance of Internet addiction.

PMID- 24866727
TI  - Sibling relationship patterns and their associations with child competence and
      problem behavior.
AB  - The present study is the first to examine patterns in sibling relationship
      quality and the associations of these patterns with internalizing and
      externalizing problem behavior, as well as self-perceived competence, in middle
      childhood. Self-report questionnaires (e.g., Sibling Relationship Questionnaire,
      Self-Perception Profile for Children, Youth Self Report) were administered among
      1,670 Dutch children (Mage = 11.40 years, SD = .83) attending 51 different Dutch
      schools. Three sibling relationship clusters were found: a conflictual cluster
      (low on warmth, high on conflict), an affect-intense cluster (above average on
      warmth and conflict), and a harmonious cluster (high on warmth, low on conflict).
      Sister pairs were underrepresented in the conflictual cluster and overrepresented
      in the harmonious cluster. Children with conflictual sibling relationships
      reported significantly more internalizing and externalizing problems, and lower
      academic and social competence and global self-worth, than children with
      harmonious sibling relationships. Children with affect-intense sibling
      relationships reported less aggression and better social competence than children
      with conflictual sibling relationships. Our findings indicate that it is fruitful
      to combine indices of sibling warmth and conflict to examine sibling relationship
      types. Relationship types differed significantly concerning internalizing and
      externalizing problems, but also concerning self-perceived competence. These
      findings extend our knowledge about sibling relationship types and their impact
      on different aspects of child adjustment. Whereas harmonious sibling
      relationships are the most beneficial for adjustment, sibling conflict mainly has
      a negative effect on adjustment in combination with lack of sibling warmth.
      Implications and future directions are discussed.

PMID- 24866728
TI  - Compassionate love as a mechanism linking sacred qualities of marriage to older
      couples' marital satisfaction.
AB  - Previous work has underscored the robust links between sanctification of marriage
      and marital outcomes, and recent developments in the literature suggest that
      compassionate love, which is important for intimate relationships, may act as a
      mediator of that relationship. Accordingly, the current study used actor-partner
      interdependence models to examine the relationship between a spiritual cognition
      (i.e., perceived sacred qualities of marriage) and marital satisfaction, and to
      determine whether that relationship is mediated by compassionate love, in a
      sample of older married couples (N = 64). Results revealed that wives' greater
      sacred qualities of marriage were significantly and positively linked to marital
      satisfaction on the part of both spouses, and that these links were partially
      mediated by couples' reports of compassionate love. These findings highlight the
      importance of moving beyond simply establishing the existence of the link between
      global markers of involvement of religion and marriage to understanding how
      specific spiritual cognitions may foster better relationship quality, especially
      among older couples.

PMID- 24866729
TI  - Unraveling the electronic structure of azolehemiporphyrazines: direct
      spectroscopic observation of magnetic dipole allowed nature of the lowest pi-pi*
      transition of 20pi-electron porphyrinoids.
AB  - Hemiporphyrazines are a large family of phthalocyanine analogues in which two
      isoindoline units are replaced by other rings. Here we report unambiguous
      identification of 20pi-electron structure of triazolehemiporphyrazines (1, 2) and
      thiazolehemiporphyrazine (3) by means of X-ray analysis, various spectroscopic
      methods, and density functional theory (DFT) calculations. The hemiporphyrazines
      were compared in detail with dibenzotetraazaporphyrin (4), a structurally related
      18pi-electron molecule. X-ray analysis revealed that tetrakis(2,6
      dimethylphenyloxy)triazolehemiporphyrazine (1b) adopted planar geometry in the
      solid state. A weak absorption band with a pronounced vibronic progression,
      observed for all the hemiporphyrazines, was attributed to the lowest pi-pi*
      transition with the electric-dipole-forbidden nature. In the case of
      intrinsically chiral vanadyl triazolehemiporphyrazine (2), a large dissymmetry
      (g) factor was detected for the CD signal corresponding to the lowest pi-pi*
      transition with the magnetic-dipole-allowed nature. Molecular orbital analysis
      and NICS calculations showed that the azolehemiporphyrazines have a 20pi-electron
      system with a weak paratropic ring current. 

PMID- 24866734
TI  - Interns' Day in Surgery: improving intern performance through a simulation-based
      course for final year medical students.
AB  - BACKGROUND: The transition from final year medical student into the first year of
      clinical practice is known to be associated with anxiety and stress that
      ultimately affects job performance. Studies have shown that much of this stress
      and anxiety results from a junior doctor's lack of confidence in performing a
      number of basic tasks. We investigated if implementation of a half-day simulation
      based course in the final year medical students results in increased confidence
      in performing these tasks. METHODS: Final year medical students of the University
      of Tasmania's School of Medicine posted at the Royal Hobart Hospital participated
      in a half-day simulation course, comprised of multiple simulation stations, which
      required students to perform the basic tasks a competent surgical intern would be
      expected to complete. Students completed a survey which investigated their
      confidence with each task before and after the course. RESULTS: Overall, the
      majority of students thought that the Interns' Day in Surgery course was useful.
      The most significant improvements perceived were in case presentation (57.5% to
      94.6%; P = 0.02) and communication with patients and other professional
      colleagues (55.5% to 75.5%; P = 0.01). A follow-up survey of doctors who attended
      this course reinforced its benefits. CONCLUSION: Simulation-based courses in
      clinical practice provide good learning opportunities for final year medical
      students within the curriculum. This study confirms significant gains in all
      skills categories practised during the course with perceived benefits
      subsequently identified by interns. This should lead to a less stressful and more
      successful transition from student to doctor and ultimately, better patient care.

PMID- 24866730
TI  - The postprandial situation as a pro-inflammatory condition.
AB  - Postprandial lipemia has been associated with cardiovascular disease. The current
      pathophysiological concept is that postprandial remnant lipoproteins migrate into
      the subendothelial space and that remnants activate circulating leukocytes and
      endothelial cells. Activated monocytes adhere to endothelial adhesion molecules,
      facilitating subendothelial migration of monocytes. These cells differentiate
      into macrophages, with the risk of foam cell formation, due to uptake of remnants
      and modified lipoproteins. Evidence is emerging that specific interventions may
      reduce the atherogenic postprandial inflammation. Fruits rich in polyphenols,
      virgin olive oil, carotenoids and exercise have recently been found to reduce
      postprandial inflammation. Pharmaceutical interventions with fibrates or statins
      not only improve the overall lipid profile, but reduce postprandial inflammation
      as well. This review will deal with the current concept of postprandial
      inflammation in relation to the development of atherosclerosis and potential
      interventions to reduce postprandial inflammation. 

PMID- 24866735
TI  - De novo donor-specific HLA antibodies: biomarkers of pancreas transplant failure.
AB  - This study assesses the role of posttransplant HLA antibody monitoring in the
      surveillance of pancreas transplant recipients. Four hundred thirty-three
      pancreas transplants were performed at the Oxford Transplant Centre 2006-2011
      (317 simultaneous pancreas kidney [SPK] and 116 isolated pancreas [IP]). HLA
      antibody monitoring was performed at 0, 6 and 12 months and annually and during
      clinical events. There was no association between pancreas graft failure and
      recipient or donor characteristics. Posttransplant antibody status, available for
      354 (81.8%) of recipients, demonstrated that 141 (39.8%) developed de novo HLA
      antibodies, of which 52 (36.9%) were de novo donor-specific HLA antibodies (DSA)
      (34 SPK, 18 IP). The development of antibodies to donor HLA, but not to nondonor
      HLA, was significantly associated with poorer graft outcomes, with 1- and 3-year
      graft survival inferior in SPK recipients (85.2% vs. 93.5%; 71.8% vs. 90.3%,
      respectively; log-rank p = 0.002), and particularly in IP recipients (50.0% vs.
      82.9%; 16.7 vs. 79.4%, respectively; log-rank p = 0.001). In a multivariate
      analysis, development of de novo DSA emerged as a strong independent predictor of
      pancreas graft failure (hazard ratio 4.66, p < 0.001). This is the largest study
      to examine de novo HLA antibodies following pancreas transplantation and clearly
      defines a high-risk group in need of specific intervention. 

PMID- 24866740
TI  - Facet-specific assembly of proteins on SrTiO3 polyhedral nanocrystals.
AB  - Precisely controlling the protein-nanomaterial interactions at selective sites is
      crucial in engineering biomolecule composite architectures with tailored
      nanostructures and functions for a variety of biomedical applications. This
      strategy, however, is only beginning to be explored. Here, we demonstrate the
      facet-specific assembly of proteins, such as albumin, immunoglobulin and
      protamine, on {100} facets of SrTiO3 polyhedral nanocrystals, while none on {110}
      facets. Molecular dynamics simulations indicate the immobile surface hydration
      layer might play a barrier role to effectively prevent proteins adsorption on
      specific {110} facets. This work thus provides new insights into the
      fundamentally understanding of protein-nanomaterial interactions, and open a
      novel, general and facile route to control the selective adsorption of various
      proteins on various nanocrystals. 

PMID- 24866746
TI  - Alcohol problems among migrants in substance use treatment: the role of drinking
      patterns in countries of birth.
AB  - Migrants' beliefs about when to seek help for alcohol problems may differ from
      host-country norms. We undertook an audit of 393 cases of screening in specialist
      alcohol and other drug services in Victoria, Australia, to examine whether
      alcohol problem severity at the time of help-seeking was influenced by drinking
      norms in countries of birth. Alcohol problem severity was measured using the
      Alcohol Use Disorders Identification Test, and World Health Organization per
      capita alcohol consumption data was used to form three categories of clients
      relative to Australian consumption: (1) Australian born; (2) born in low alcohol
      consumption countries; and (3) born in high alcohol consumption countries.
      Clients born in high consumption countries such as those in Europe and the UK had
      significantly higher levels of alcohol problem severity at intake compared with
      Australian-born clients and clients born in low consumption countries. This
      suggests that clients from high consumption countries might have delayed seeking
      help in line with the alcohol norms in their country of origin. Screening this
      group for alcohol problems in primary health care might avoid significant
      cumulative harm. 

PMID- 24866741
TI  - Mexiletine as a treatment for primary erythromelalgia: normalization of
      biophysical properties of mutant L858F NaV 1.7 sodium channels.
AB  - BACKGROUND AND PURPOSE: The non-selective sodium channel inhibitor mexiletine has
      been found to be effective in several animal models of chronic pain and has
      become popular in the clinical setting as an orally available alternative to
      lidocaine. It remains unclear why patients with monogenic pain disorders
      secondary to gain-of-function SCN9a mutations benefit from a low systemic
      concentration of mexiletine, which does not usually induce adverse neurological
      side effects. The aim of this study was, therefore, to investigate the
      biophysical effects of mexiletine on the L858F primary erythromelalgia NaV 1.7
      mutation in vitro. EXPERIMENTAL APPROACH: Human wild-type and L858F-mutated NaV
      1.7 channels were expressed in HEK293A cells. Whole-cell currents were recorded
      by voltage-clamp techniques to characterize the effect of mexiletine on channel
      gating properties. KEY RESULTS: While the concentration-dependent tonic block of
      peak currents by mexiletine was similar in wild-type and L858F channels, phasic
      block was more pronounced in cells transfected with the L858F mutation. Moreover,
      mexiletine substantially shifted the pathologically-hyperpolarized voltage
      dependence of steady-state activation in L858F-mutated channels towards wild-type
      values and the voltage-dependence of steady-state fast inactivation was shifted
      to more hyperpolarized potentials, leading to an overall reduction in window
      currents. CONCLUSION AND IMPLICATIONS: Mexiletine has a normalizing effect on the
      pathological gating properties of the L858F gain-of-function mutation in NaV 1.7,
      which, in part, might explain the beneficial effects of systemic treatment with
      mexiletine in patients with gain-of-function sodium channel disorders.

PMID- 24866747
TI  - Pediatric Crohn's disease from onset to adulthood: granulomas are associated with
      an early need for immunomodulation.
AB  - OBJECTIVE: Childhood onset Crohn's disease (CD) is considered more aggressive
      than adult onset disease. Epithelioid cell granulomas in intestinal biopsies are
      one, non-obligate, criterion of CD. We investigated granulomas as markers of CD
      severity in children followed to adulthood. MATERIAL AND METHODS: Forty-five
      individuals with childhood onset CD were studied from diagnosis until attainment
      of final height, with data on disease location, medical and surgical management
      and with detailed growth data analyses. A blinded review of diagnostic biopsies
      was also performed. RESULTS: We found granulomas in 22/45 (49%) children at
      diagnosis, altogether in 28/45 (62%) patients during the disease course (median
      overall follow-up - 12.3 years, range 9.3-18). Granulomas were found in 9/11
      (82%) with upper gastrointestinal involvement (cumulatively 17/20, 85%) (p =
      0.017 and p = 0.006, respectively). The time from diagnosis to initiating immune
      modulating treatment (median 4.5 months, range 0-75) was shorter in the granuloma
      positive group (16/22) compared to the granuloma-negative group (18/23) (median
      33 months, range 2-105; p = 0.01). The median standard deviation score height at
      diagnosis and final adult height (both adjusted for target height) did not
      correlate to findings of granulomas. CONCLUSIONS: Epithelioid cell granulomas
      were associated with a shorter time to initiating immune modulating drugs, as a
      possible sign of more severe disease, but growth was not affected.

PMID- 24866748
TI  - Convection-enhanced delivery of AAV2-PrPshRNA in prion-infected mice.
AB  - Prion disease is caused by a single pathogenic protein (PrPSc), an abnormal
      conformer of the normal cellular prion protein PrPC. Depletion of PrPC in prion
      knockout mice makes them resistant to prion disease. Thus, gene silencing of the
      Prnp gene is a promising effective therapeutic approach. Here, we examined adeno
      associated virus vector type 2 encoding a short hairpin RNA targeting Prnp mRNA
      (AAV2-PrP-shRNA) to suppress PrPC expression both in vitro and in vivo. AAV2-PrP
      shRNA treatment suppressed PrP levels and prevented dendritic degeneration in RML
      infected brain aggregate cultures. Infusion of AAV2-PrP-shRNA-eGFP into the
      thalamus of CD-1 mice showed that eGFP was transported to the cerebral cortex via
      anterograde transport and the overall PrPC levels were reduced by ~ 70% within 4
      weeks. For therapeutic purposes, we treated RML-infected CD-1 mice with AAV2-PrP
      shRNA beginning at 50 days post inoculation. Although AAV2-PrP-shRNA focally
      suppressed PrPSc formation in the thalamic infusion site by ~ 75%, it did not
      suppress PrPSc formation efficiently in other regions of the brain. Survival of
      mice was not extended compared to the untreated controls. Global suppression of
      PrPC in the brain is required for successful therapy of prion diseases.

PMID- 24866750
TI  - Mechano-responsive gelation of water by a short alanine-derivative.
AB  - We report the design of a structurally concise alanine derivative (Ala-hyd) that
      has a rotationally flexible aromatic N-protecting group for alanine and a
      hydrazide functionality at its carboxylic end. Ala-hyd requires mechanical
      agitation (physically stirring, vortexing or sonicating) to form supramolecular
      hydrogels at medium concentrations (0.4-0.8 wt%). At higher concentrations (>0.8
      wt%), it spontaneously gelates water on undisturbed cooling of the hot solution,
      while at lower concentrations (<0.4 wt%), only turbid suspensions were formed
      upon agitation. In the <0.8 wt% regime, hydrogelation by Ala-hyd is modulated by
      its concentration as well as by the extent of applied mechanical agitation.
      Turbidimetry and fluorescence spectroscopy indicate enhanced self-assembly of Ala
      hyd upon agitation, and FTIR studies point towards stronger hydrogen bonds in the
      resulting assemblies. Since Ala-hyd requires mechanical agitation to undergo self
      assembly, its aqueous sols exhibited mild shear-thickening behaviour in buffered
      as well as salt-free conditions. During shearing, the formation of an entangled
      mesh of long, helical nanofibers coincided with the maximum in the bulk shear
      viscosity. pH-dependent rheological investigations indicate that protonation of
      the amine unit (pKa = 8.9) of hydrazide diminishes the self-assembly propensity
      of this compound. The self-assembly of Ala-hyd can thus be modulated through
      mechanical as well as chemical cues. 

PMID- 24866749
TI  - Buggy Creek virus (Togaviridae: Alphavirus) upregulates expression of pattern
      recognition receptors and interferons in House Sparrows (Passer domesticus).
AB  - Birds serve as reservoirs for at least 10 arthropod-borne viruses, yet specific
      immune responses of birds to arboviral infections are relatively unknown. Here,
      adult House Sparrows were inoculated with an arboviral alphavirus, Buggy Creek
      virus (BCRV), or saline, and euthanized between 1 and 3 days postinoculation.
      Virological dynamics and gene expression dynamics were investigated. Birds did
      not develop viremia postinoculation, but cytopathic virus was found in the
      skeletal muscle and spleen of birds 1 and 3 days postinoculation (DPI). Viral RNA
      was detected in the blood of BCRV-infected birds 1 and 2 DPI, in oral swabs 1-3
      DPI, and in brain, heart, skeletal muscle, and spleen 1-3 DPI. Multiple genes
      were significantly upregulated following BCRV infection, including pattern
      recognition receptors (TLR7, TLR15, RIG-1), type I interferon (IFN-alpha), and
      type II interferon (IFN-gamma). This is the first study to report avian
      immunological gene expression profiles following an arboviral infection.

PMID- 24866752
TI  - Sildenafil for pulmonary hypertension complicating bronchopulmonary dysplasia.
AB  - Sildenafil, a phospohodiesterase-5 inhibitor, is widely used to treat pulmonary
      hypertension in infants with bronchopulmonary dysplasia despite a lack of
      evidence to support either safety or efficacy and US FDA advice against its use.

PMID- 24866751
TI  - Decellularization of fibroblast cell sheets for natural extracellular matrix
      scaffold preparation.
AB  - The application of cell-derived extracellular matrix (ECM) in tissue engineering
      has gained increasing interest because it can provide a naturally occurring,
      complex set of physiologically functional signals for cell growth. The ECM
      scaffolds produced from decellularized fibroblast cell sheets contain high
      amounts of ECM substances, such as collagen, elastin, and glycosaminoglycans.
      They can serve as cell adhesion sites and mechanically strong supports for tissue
      engineered constructs. An efficient method that can largely remove cellular
      materials while maintaining minimal disruption of ECM ultrastructure and content
      during the decellularization process is critical. In this study, three
      decellularization methods were investigated: high concentration (0.5 wt%) of
      sodium dodecyl sulfate (SDS), low concentration (0.05 wt%) of SDS, and freeze
      thaw cycling method. They were compared by characterization of ECM preservation,
      mechanical properties, in vitro immune response, and cell repopulation ability of
      the resulted ECM scaffolds. The results demonstrated that the high SDS treatment
      could efficiently remove around 90% of DNA from the cell sheet, but significantly
      compromised their ECM content and mechanical strength. The elastic and viscous
      modulus of the ECM decreased around 80% and 62%, respectively, after the high SDS
      treatment. The freeze-thaw cycling method maintained the ECM structure as well as
      the mechanical strength, but also preserved a large amount of cellular components
      in the ECM scaffold. Around 88% of DNA was left in the ECM after the freeze-thaw
      treatment. In vitro inflammatory tests suggested that the amount of DNA fragments
      in ECM scaffolds does not cause a significantly different immune response. All
      three ECM scaffolds showed comparable ability to support in vitro cell
      repopulation. The ECM scaffolds possess great potential to be selectively used in
      different tissue engineering applications according to the practical requirement.

PMID- 24866754
TI  - A study on the versatility of metallacycles in host-guest chemistry: interactions
      in halide-centered hexanuclear copper(II) pyrazolate complexes.
AB  - Hexanuclear copper(II) pyrazolate complexes have shown the ability to encapsulate
      different halide ions, leading to [trans-Cu6{MU-3,5-(CF3)2pz}6(MU-OH)6X](-) (X =
      F, Cl, Br, I). They offer an interesting case study for variation in local
      properties at host binding sites, due to the presence of a six membered ring
      involving Cu(II) centers considered as the borderline Lewis acid according to the
      Pearson Hard and Soft Acids and Bases (HSAB) principle. Here, we describe the
      host-guest interactions via relativistic density functional calculations,
      involving the graphical description of local dipole and quadrupole moments,
      energy decomposition analysis, non-covalent indices, and magnetic behavior. The
      observed variation in the copper local dipole and quadrupole moments suggests
      that a metallacycle host offers great advantages in comparison to their organic
      counterparts, prompted by the versatility of the metallic centers to modulate the
      surrounding electron density accordingly. According to our results, the
      contribution of ion-dipole forces in the halide-centered series decreases from
      95.0% to 77.0% from the fluoride to the iodide complex, whereas the contribution
      of higher order interactions such as quadrupole-dipole and quadrupole-quadrupole,
      goes from 5.0% to 23.0% towards a softer guest. In addition, the through-the
      space magnetic response of trans-Cu6{MU-3,5-(CF3)2pz}6(MU-OH)6, reveals a
      noteworthy aromatic structure, which is driven by the superexchange through the
      ligands leading to a singlet ground state.

PMID- 24866753
TI  - Quantification of myocardial salvage by myocardial perfusion SPECT and cardiac
      magnetic resonance--reference standards for ECG development.
AB  - In order to determine the cardioprotective efficacy of acute reperfusion therapy,
      assessed as myocardial salvage, in patients with acute coronary occlusion, the
      final myocardial infarct (MI) size needs to be related to the amount of ischemic
      myocardium during coronary occlusion, referred to as the myocardium at risk
      (MaR). There are currently several imaging approaches available for
      quantification of both MI size and MaR in vivo of which some have been validated
      both in pre-clinical and clinical settings. These methods often involve the use
      of either myocardial perfusion SPECT or cardiac magnetic resonance (CMR). These
      imaging methods could potentially be used to further develop and validate ECG
      methods for determination of MI size and MaR. Therefore, the aim of the present
      review is to give an overview of myocardial perfusion SPECT and CMR methods
      available for assessment of myocardial salvage by determination of MI size and
      MaR. 

PMID- 24866755
TI  - Assessment of mean platelet volume and soluble CD40 ligand levels in patients
      with non-dipper hypertension, dippers and normotensives.
AB  - Abstract Objective: Patients with a lack of nocturnal decline in blood pressure
      (BP) are at an increased risk for cardiovascular events. Mean platelet volume
      (MPV) and soluble CD40 ligand (sCD40L) are accepted biomarkers of platelet
      activation and considered as a risk factor for cardiovascular disease. The aim of
      this study was to determine whether MPV and sCD40L levels are higher in non
      dipper hypertensive (NDHT) patients than in dipper hypertensive (DHT) patients
      and healthy controls. METHODS: 124 consecutive patients were included to this
      study. Patients were divided into three groups: NDHT patient group [n = 43; mean
      age 51.8 +/- 6.6; 31 males (72.1%)]; DHT patient group [n = 41; mean age 50.2 +/-
      7.3; 22 males (53.7%)]; and normotensive group [n = 40; mean age 49.9 +/- 6.7; 22
      males (55%)]. Physical examination, laboratory work-up and 24-h ABPM were
      performed for all participants. RESULTS: The sCD40L and MPV levels were
      significantly higher in the NDHT group than in the DHT and normotensive groups (p
      < 0.05). In correlation analysis, MPV, 24-h systolic blood pressure (SBP), 24-h
      diastolic blood pressure (DBP), night-time SBP and night-time DBP were positively
      correlated with sCD40L. CONCLUSION: Our study demonstrated that MPV and sCD40L
      levels were significantly higher in NDHT patients compared to DHT and
      normotensive patients. sCD40L levels were positively correlated with MPV, 24-h
      SBP, 24-h DBP, night-time SBP and night-time DBP.

PMID- 24866757
TI  - Translational genomics: A network of the human metabolome.

PMID- 24866756
TI  - The dawn of evolutionary genome engineering.
AB  - Genome engineering strategies--such as genome editing, reduction and shuffling,
      and de novo genome synthesis--enable the modification of specific genomic
      locations in a directed and combinatorial manner. These approaches offer an
      unprecedented opportunity to study central evolutionary issues in which natural
      genetic variation is limited or biased, which sheds light on the evolutionary
      forces driving complex and extremely slowly evolving traits; the selective
      constraints on genome architecture; and the reconstruction of ancestral states of
      cellular structures and networks.

PMID- 24866758
TI  - Retrospective studies of end-of-life resource utilization and costs in cancer
      care using health administrative data: a systematic review.
AB  - BACKGROUND: There has been an increase in observational studies using health
      administrative data to examine the nature, quality, and costs of care at life's
      end, particularly in cancer care. AIM: To synthesize retrospective observational
      studies on resource utilization and/or costs at the end of life in cancer
      patients. We also examine the methods and outcomes of studies assessing the
      quality of end-of-life care. DESIGN: A systematic review according to PRISMA
      (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and AMSTAR
      (A Measurement Tool to Assess Systematic Reviews) methodology. DATA SOURCES: We
      searched MEDLINE, Embase, CINAHL, and York Centre for Research and Dissemination
      (1990-2011). Independent reviewers screened abstracts of 14,424 articles, and 835
      full-text manuscripts were further reviewed. Inclusion criteria were English
      language; at least one resource utilization or cost outcome in adult cancer
      decedents with solid tumors; outcomes derived from health administrative data;
      and an exclusive end-of-life focus. RESULTS: We reviewed 78 studies examining end
      of-life care in over 3.7 million cancer decedents; 33 were published since 2008.
      We observed exponential increases in service use and costs as death approached;
      hospital services being the main cost driver. Palliative services were relatively
      underutilized and associated with lower expenditures than hospital-based care.
      The 15 studies using quality indicators demonstrated that up to 38% of patients
      receive chemotherapy or life-sustaining treatments in the last month of life and
      up to 66% do not receive hospice/palliative services. CONCLUSION: Observational
      studies using health administrative data have the potential to drive evidence
      based palliative care practice and policy. Further development of quality care
      markers will enhance benchmarking activities across health care jurisdictions,
      providers, and patient populations.

PMID- 24866759
TI  - Hospitalizations of nursing home residents with dementia in the last month of
      life: results from a nationwide survey.
AB  - BACKGROUND: Hospitalizations of nursing home residents with dementia may not be
      uncommon. However, evidence from epidemiological studies outside the United
      States and knowledge about the circumstances of hospitalizations are lacking.
      AIM: To examine the proportion of nursing home residents with dementia
      hospitalized in the last month of life and factors associated with
      hospitalization. DESIGN: The design is stratified cluster sampling survey. Nurses
      retrospectively registered demographic and dementia-related information about
      deceased residents with dementia. This included information about
      hospitalizations, persons involved in hospitalization decisions and type and
      content of information transferred when hospitalized. SETTING/PARTICIPANTS:
      Nursing home residents dying with dementia in Belgium (Flanders) in 2010.
      RESULTS: In the final month of life, 19.5% of nursing home residents dying with
      dementia (N = 198) were hospitalized, including 4.6% admitted to an intensive
      care unit. For 12.2% of residents dying with dementia, a do-not-hospitalize
      advance directive was present, for 57.0%, a do-not-hospitalize general physician
      order. Residents without a do-not-hospitalize general physician-order were more
      likely of being hospitalized (adjusted odds ratio: 3.4; 95% confidence interval:
      1.3-8.7). None of the hospitalizations occurred at the request of the resident;
      37% were at the request of relatives; curative or life-prolonging treatments were
      the most frequent reasons given. Information about the resident's nursing care or
      medical treatment was transferred in almost all hospitalizations, information
      about wishes and preferences for future care in 19%. CONCLUSION: Hospitalization
      in Belgian nursing home residents with dementia in the last month of life was
      common. Documentation of do-not-hospitalize physician-orders in the resident's
      medical files may prevent hospitalizations.

PMID- 24866765
TI  - Invasive cutaneous squamous cell carcinoma incidence in US health care workers.
AB  - Little data on cutaneous squamous cell carcinoma (SCC) epidemiology within the
      United States are currently available. Prior studies have focused on populations
      outside of the United States or been limited to regions within the US. In this
      study, prospective data were collected via biennial questionnaires from a total
      of 261,609 participants, which included women in the Nurses' Health Study (NHS,
      1976-2008) and Nurses' Health Study II (NHS II, 1989-2009), and men in the Health
      Professionals Follow-Up Study (HPFS, 1986-2008). History of physician-diagnosed
      invasive SCC was confirmed by pathology record review. Over the entire follow-up
      period for each cohort, there were 1,265 invasive SCC cases per 100,000 persons
      in the NHS cohort, 389 cases per 100,000 persons in NHS II, and 2,154 cases per
      100,000 persons in HPFS. An 18-year follow-up of participants in these cohorts
      revealed increasing invasive SCC incidence rates over time, with rates for men
      being consistently higher than those for women. In women, a larger proportion of
      invasive SCC lesions occurred on the lower extremities as compared to men (21 %
      in NHS vs. 6 % in HPFS, p < 0.0001; 14 % in NHS II vs. 6 % in HPFS, p < 0.0001),
      while in men, a larger proportion occurred on the head/neck (43 % in NHS vs. 60 %
      in HPFS, p < 0.0001; 48 % in NHS II vs. 60 % in HPFS, p < 0.0001). In summary,
      invasive SCC incidence rates among US men have been greater than those for women
      with distinct sites of common occurrence between men and women.

PMID- 24866768
TI  - Facilitation of endoglin-targeting cancer therapy by development/utilization of a
      novel genetically engineered mouse model expressing humanized endoglin (CD105).
AB  - Endoglin (ENG) is a TGF-beta coreceptor and essential for vascular development
      and angiogenesis. A chimeric antihuman ENG (hENG) monoclonal antibody (mAb) c
      SN6j (also known as TRC105) shows promising safety and clinical efficacy features
      in multiple clinical trials of patients with various advanced solid tumors. Here
      we developed a novel genetically engineered mouse model to optimize the ENG
      targeting clinical trials. We designed a new targeting vector that contains exons
      4-8 of hENG gene to generate novel genetically engineered mice (GEMs) expressing
      functional human/mouse chimeric (humanized) ENG with desired epitopes. Genotyping
      of the generated mice confirmed that we generated the desired GEMs.
      Immunohistochemical analysis demonstrated that humanized ENG protein of the GEMs
      expresses epitopes defined by 7 of our 8 anti-hENG mAbs tested. Surprisingly the
      homozygous GEMs develop normally and are healthy. Established breast and colon
      tumors as well as metastasis and tumor microvessels in the GEMs were effectively
      suppressed by systemic administration of anti-hENG mAbs. Additionally, test
      result indicates that synergistic potentiation of antitumor efficacy can be
      induced by simultaneous targeting of two distinct epitopes by anti-hENG mAbs.
      Sorafenib and capecitabine also showed antitumor efficacy in the GEMs. The
      presented novel GEMs are the first GEMs that express the targetable humanized
      ENG. Test results indicate utility of the GEMs for the clinically relevant
      studies. Additionally, we generated GEMs expressing a different humanized ENG
      containing exons 5-6 of hENG gene, and the homozygous GEMs develop normally and
      are healthy. 

PMID- 24866769
TI  - MTBP is overexpressed in triple-negative breast cancer and contributes to its
      growth and survival.
AB  - Triple-negative breast cancer (TNBC) is a clinically aggressive subtype of breast
      cancer commonly resistant to therapeutics that have been successful in increasing
      survival in patients with estrogen receptor-positive (ER(+)) and HER2(+) breast
      cancer. As such, identifying factors that contribute to poor patient outcomes and
      mediate the growth and survival of TNBC cells remain important areas of
      investigation. MTBP (MDM2-binding protein), a gene linked to cellular
      proliferation and a transcriptional target of the MYC oncogene, is overexpressed
      in human malignancies, yet its contribution to cancer remains unresolved.
      Evaluation of mRNA expression and copy number variation data from The Cancer
      Genome Atlas (TCGA) revealed that MTBP is commonly overexpressed in breast cancer
      and 19% show amplification of MTBP. Increased transcript or gene amplification of
      MTBP significantly correlated with reduced breast cancer patient survival.
      Further analysis revealed that while MTBP mRNA is overexpressed in both ER(+) and
      HER2(+) breast cancers, its expression is highest in TNBC. MTBP mRNA and protein
      levels were also significantly elevated in a panel of human TNBC cell lines.
      Knockdown of MTBP in TNBC cells induced apoptosis and significantly reduced TNBC
      cell growth and soft agar colony formation, which was rescued by expression of
      shRNA-resistant Mtbp. Notably, inducible knockdown of MTBP expression
      significantly impaired TNBC tumor growth, in vivo, including in established
      tumors. Thus, these data emphasize that MTBP is important for the growth and
      survival of TNBC and warrants further investigation as a potential novel
      therapeutic target. IMPLICATIONS: MTBP significantly contributes to breast cancer
      survival and is a potential novel therapeutic target in TNBC.

PMID- 24866763
TI  - Integration of mRNA expression profile, copy number alterations, and microRNA
      expression levels in breast cancer to improve grade definition.
AB  - Defining the aggressiveness and growth rate of a malignant cell population is a
      key step in the clinical approach to treating tumor disease. The correct grading
      of breast cancer (BC) is a fundamental part in determining the appropriate
      treatment. Biological variables can make it difficult to elucidate the mechanisms
      underlying BC development. To identify potential markers that can be used for BC
      classification, we analyzed mRNAs expression profiles, gene copy numbers,
      microRNAs expression and their association with tumor grade in BC microarray
      derived datasets. From mRNA expression results, we found that grade 2 BC is most
      likely a mixture of grade 1 and grade 3 that have been misclassified, being
      described by the gene signature of either grade 1 or grade 3. We assessed the
      potential of the new approach of integrating mRNA expression profile, copy number
      alterations, and microRNA expression levels to select a limited number of genomic
      BC biomarkers. The combination of mRNA profile analysis and copy number data with
      microRNA expression levels led to the identification of two gene signatures of 42
      and 4 altered genes (FOXM1, KPNA4, H2AFV and DDX19A) respectively, the latter
      obtained through a meta-analytical procedure. The 42-based gene signature
      identifies 4 classes of up- or down-regulated microRNAs (17 microRNAs) and of
      their 17 target mRNA, and the 4-based genes signature identified 4 microRNAs (Hsa
      miR-320d, Hsa-miR-139-5p, Hsa-miR-567 and Hsa-let-7c). These results are
      discussed from a biological point of view with respect to pathological features
      of BC. Our identified mRNAs and microRNAs were validated as prognostic factors of
      BC disease progression, and could potentially facilitate the implementation of
      assays for laboratory validation, due to their reduced number. 

PMID- 24866772
TI  - The use of Bayesian inference to inform the surveillance of temperature-related
      occupational morbidity in Ontario, Canada, 2004-2010.
AB  - PURPOSE: To assess the associations of occupational heat and cold-related
      illnesses presenting in emergency departments in south western Ontario, Canada,
      with daily meteorological conditions using Bayesian inference. METHODOLOGY:
      Meteorological and air pollution data for the south western economic region of
      Ontario were gathered from Environment Canada and the Ministry of Environment.
      Daily heat and cold-related emergency department visits clinically attributed to
      work from 2004 to 2010 were tabulated. A novel application of Bayesian inference
      on a flexible Poisson time series model was undertaken to examine linear and non
      linear associations between average, regional meteorological conditions and daily
      morbidity rates, to adjust for relevant confounders and temporal trends, and to
      consider potential interactions. RESULTS: Bilinear associations were observed
      between regional temperatures and morbidities resulting from extreme temperature
      exposures. The median increase in the daily rate of emergency department visits
      for heat illness was 75% for each degree above 22 degrees C (posterior 95%
      credible interval (CI) relative rate=1.56-1.99) in the daily maximum temperature.
      Below 0 degrees C, rates of occupational cold illness increased by a median of
      15% for each degree decrease in the minimum temperature (posterior 95% CI 0.80
      0.91); wind speed also had a significant effect. CONCLUSIONS: The observed
      associations can inform occupational surveillance and injury prevention
      programming, as well as public health efforts targeting vulnerable populations.
      Methodologically, the use of Bayesian inference in time series analyses of
      meteorological exposures is feasible and conducive to providing accurate advice
      for policy and practice.

PMID- 24866770
TI  - SIRT2 interacts with beta-catenin to inhibit Wnt signaling output in response to
      radiation-induced stress.
AB  - Wnt signaling is critical to maintaining cellular homeostasis via regulation of
      cell division, mitigation of cell stress, and degradation. Aberrations in Wnt
      signaling contribute to carcinogenesis and metastasis, whereas sirtuins have
      purported roles in carcinogenesis, aging, and neurodegeneration. Therefore, the
      hypothesis that sirtuin 2 (SIRT2) directly interacts with beta-catenin and
      whether this interaction alters the expression of Wnt target genes to produce an
      altered cellular phenotype was tested. Coimmunoprecipitation studies, using mouse
      embryonic fibroblasts (MEF) from Sirt2 wild-type and genomic knockout mice,
      demonstrate that beta-catenin directly binds SIRT2. Moreover, this interaction
      increases in response to oxidative stress induced by ionizing radiation. In
      addition, this association inhibits the expression of important Wnt target genes
      such as survivin (BIRC5), cyclin D1 (CCND1), and c-myc (MYC). In Sirt2 null MEFs,
      an upregulation of matrix metalloproteinase 9 (MMP9) and decreased E-cadherin
      (CDH1) expression is observed that produces increased cellular migration and
      invasion. Together, these data demonstrate that SIRT2, a tumor suppressor lost in
      multiple cancers, inhibits the Wnt signaling pathway in nonmalignant cells by
      binding to beta-catenin and that SIRT2 plays a critical role in the response to
      oxidative stress from radiation. IMPLICATIONS: Disruption of the SIRT2-beta
      catenin interaction represents an endogenous therapeutic target to prevent
      transformation and preserve the integrity of aging cells against exogenous
      stressors such as reactive oxygen species.

PMID- 24866773
TI  - Utilization of whole cell mediated deracemization in a chemoenzymatic synthesis
      of enantiomerically enriched polycyclic chromeno[4,3-b] pyrrolidines.
AB  - Various aryl and alkyl substituted optically pure propargyl alcohols were
      obtained with excellent ee (up to >99%) and isolated yields (up to 87%) by
      deracemization using whole cells of Candida parapsilosis ATCC 7330. The whole
      cells show substrate specificity towards alkyl substituted propargyl alcohols and
      a switch in the enantioselectivity has been observed from 'R' to 'S' upon
      increasing the chain length. For the first time, enantiopure (R)-4-(3-hydroxybut
      1-ynyl)benzonitrile, (R)-4-(biphenyl-4-yl)but-3-yn-2-ol, (S)-ethyl 3-hydroxy-5
      phenylpent-4-ynoate and (S)-4-phenylbut-3-yne-1,2-diol were obtained using this
      strategy. Optically pure propargyl alcohol thus obtained was used as a chiral
      starting material in the synthesis of enantiomerically enriched poly-substituted
      pyrrolidines and a pyrrole derivative successfully demonstrating a chemoenzymatic
      route. 

PMID- 24866775
TI  - Antiplatelet therapy in critical limb ischemia: update on clopidogrel and
      cilostazol.
AB  - Antiplatelet therapy is essential for critical limb ischemia (CLI) patients, both
      as primary prevention for ischemic events and as adjuvant pharmacotherapy in
      order to avoid acute or late thrombo-occlusive events and maintain patency
      following peripheral endovascular or open surgical limb-salvage revascularization
      procedures. According to currently updated international guidelines clopidogrel
      as monotherapy or as part of dual antiplatelet therapy is recommended in CLI
      patients, while recent evidence delineated the beneficial effect of cilostazol in
      patients undergoing peripheral endovascular angioplasty or stenting as its
      administration resulted in a decrease of restenosis and clinically-driven
      reinterventions, as well as in the enhancement of platelet inhibition. This
      review aims in discussing recent evidence on the topic of antiplatelet therapy in
      CLI patients, with a special focus on the use of clopidogrel and cilostazol. 

PMID- 24866776
TI  - Bioresorbable scaffolds for the SFA: new developments.
AB  - The implantation of metallic stents has become a standard procedure to improve
      the outcome after angioplasty of the superficial femoral artery (SFA). However,
      the permanent presence of a metallic stent in the femoropopliteal artery is
      associated with a number of potential disadvantages. Thus, the use of a
      bioresorbable scaffold, which stabilizes the vessel for a defined period after
      implantation but is then resorbed, is a compelling concept. This review gives an
      overview on the use of bioresorbable scaffolds in the peripheral arteries, with
      an emphasis on the SFA. 

PMID- 24866774
TI  - Treatment strategies for carotid artery aneurysms.
AB  - BACKGROUND: The aim of this paper was to present single centre experience in the
      treatment of extra cranial carotid artery aneurysms (ECCA) and to analyze results
      discussing different treatment modalities. METHODS: The study analyzed 60
      patients with 62 ECCA treated surgically at the Clinic for vascular and
      endovascular surgery, Serbian Clinical Center (Belgrade) in the period between
      1985 and 2013. Treatment strategy was individually selected and demographic,
      morphologic, intraoperative and postoperative data were collected. RESULTS:
      Thirty-day operative mortality was 3.3% and completely stroke related. Besides
      two fatal strokes one additional was registered making total number of 3 (4.8%)
      postoperative strokes. Only one (1.6%) early graft thrombosis has been found. The
      30-day-patency rate was 98.4%. During the same period seven local complications
      were found: three (4.8%) hemorrhage and four (6.4%) cranial nerves injuries. In
      all cases of hemorrhage successful re-intervention was performed without any
      consequences. Cranial nerves injuries included transient contusions of
      hypoglossal (2) and superior laryngeal nerve (2). CONCLUSIONS: The etiology,
      location, and morphology of an ECCA are determining selection of appropriate
      therapy. Large or tortuous aneurysms, as well as aneurysms involving common
      carotid or proximal internal carotid artery, are also absolutely indicated to
      open surgical therapy. Aneurysms which involve the distal internal carotid artery
      and false anastomotic aneurysms are best managed with endovascular techniques.
      The ligature is indicated for the treatment of external carotid aneurysms,
      mycotic aneurysms with local infection and in ruptured ECCA with uncontrolled
      bleeding.

PMID- 24866777
TI  - Editorial overview: Growing the future: synthetic biology in plants.

PMID- 24866780
TI  - Value of endoscopic mucosal biopsies in normal-appearing colonic mucosa.

PMID- 24866781
TI  - Steps toward harmonization for clinical development of medicines in pediatric
      ulcerative colitis-a global scientific discussion, part 1: efficacy endpoints and
      disease outcome assessments.
AB  - OBJECTIVES: There is a pressing need for drug development in pediatric ulcerative
      colitis (UC). Lack of scientific consensus on efficacy endpoints and disease
      outcome assessments presents a hurdle for global drug development in pediatric
      UC. Scientists from 4 regulatory agencies convened an International Inflammatory
      Bowel Disease Working Group (i-IBD Working Group) to harmonize present thinking
      about various aspects of drug development in pediatric UC globally. METHODS: The
      i-IBD Working Group was convened in 2012 by scientists from the US Food and Drug
      Administration, European Medicines Agency, Health Canada, and the Pharmaceuticals
      and Medical Devices Agency of Japan. The members of this group considered reasons
      for differences in their acceptance of efficacy endpoints and disease activity
      indices used in pediatric UC, reviewed the available literature, and developed
      consensus opinions regarding approaches for evaluating outcomes in pediatric UC
      trials. RESULTS: There is lack of harmonization in using efficacy endpoint and
      outcome assessments including disease activity indices to assess clinical benefit
      in pediatric UC trials. Many disease activity indices have been developed, but
      their biometric properties, such as responsiveness, reliability, and validity,
      have not been properly validated. Biomarkers, such as fecal calprotectin and
      lactoferrin, are being investigated for their potential as noninvasive surrogate
      endpoints in UC. CONCLUSIONS: Consensus on the efficacy endpoints, disease
      activity indices, and outcome assessments is needed for globalization of
      pediatric UC trials. The i-IBD Working Group offers several perspectives to
      facilitate harmonization across regions. The development of noninvasive
      biomarkers as reliable surrogate endpoints needs to be explored further.

PMID- 24866782
TI  - Steps toward harmonization for clinical development of medicines in pediatric
      ulcerative colitis-a global scientific discussion, part 2: data extrapolation,
      trial design, and pharmacokinetics.
AB  - OBJECTIVES: To facilitate global drug development, the International Pediatric
      Inflammatory Bowel Disease Working Group (i-IBD Working Group) discussed data
      extrapolation, trial design, and pharmacokinetic (PK) considerations for drugs
      intended to treat pediatric ulcerative colitis (UC), and considered possible
      approaches toward harmonized drug development. METHODS: Representatives from the
      US Food and Drug Administration, European Medicines Agency, Health Canada, and
      the Pharmaceuticals and Medical Devices Agency of Japan convened monthly to
      explore existing regulatory approaches, reviewed the results of a literature
      search, and provided perspectives on pediatric UC drug development based on the
      available medical literature. RESULTS: Although pediatric UC, when compared with
      UC in adults, has a similar disease progression and response to intervention, the
      similarity of the exposure-response relation has not been adequately established.
      Consequently, clinical endpoints should be selected to optimally assess efficacy
      in children. The inclusion of a placebo control in pediatric trials to assure
      assay sensitivity may be appropriate under limited circumstances. In clinical
      studies, although the drug under investigation could provide possible direct
      benefit, placebo treatment should present no more than a minor increase over
      minimal risk to children with UC. CONCLUSIONS: Partial extrapolation of efficacy
      from informative adult studies may be appropriate. Placebo-controlled efficacy
      trials are scientifically and ethically appropriate for pediatric UC given
      appropriate patient selection and the use of early escape. Clinical studies in
      pediatric UC may include initial dose-finding studies and exposure-response
      modeling followed by an efficacy and safety study to further explore the exposure
      response relation.

PMID- 24866783
TI  - Role reversal method for treatment of food refusal associated with infantile
      feeding disorders.
AB  - OBJECTIVES: Infantile feeding disorders (IFDs) are common causes of food refusal
      and failure to thrive, and are frequently encountered by primary care physicians
      and specialists. We have published the Wolfson criteria for IFD, which have eased
      the approach to the diagnosis of IFDs. Along with and complementary to the
      Wolfson criteria, we have also developed the role reversal treatment method for
      IFD, which has been briefly described earlier. The aim of this study was to
      validate the role reversal treatment method on a cohort of infants diagnosed as
      having IFD and to present a detailed description of this method for the first
      time. METHODS: Parents of infants and children diagnosed as having IFD were
      invited to participate in the study; they were handed over a questionnaire
      comprising 6 categories of questions related to patient and parents behaviors,
      attitudes, and perceptions, which was completed at initiation and at the end of
      treatment. Full response was defined as improved normative feeding, cessation of
      abnormal parental feeding, and improved or normal growth patterns. A partial
      response was defined as success with two-third categories. RESULTS: We enrolled
      38 patients, and 32 patients completed the study. Improved feeding occurred in
      78%, full recovery was documented in 53% of infants by 6 months, and partial
      response was observed in another 25%. All forms of pathological feeding improved
      significantly (mechanistic, nocturnal, persecutory, forced feeding, and
      distraction). CONCLUSIONS: The role reversal treatment method is a simple and
      effective approach to the treatment of food refusal associated with IFD.

PMID- 24866784
TI  - Validation of the Rome III criteria and alarm symptoms for recurrent abdominal
      pain in children.
AB  - OBJECTIVES: Rome criteria were formulated to define functional gastrointestinal
      disorders (Rome III criteria, 2006) excluding organic diagnoses when alarm
      symptoms were absent. The aims of the study were to validate the Rome III
      criteria as to their capacity to differentiate between organic and functional
      abdominal pain and to assess the role of alarm symptoms in this differentiation.
      METHODS: During 2 years all of the patients (ages 4-16 years) presenting with
      recurrent abdominal pain (Apley criteria) and referred to secondary care were
      included. Clinical diagnoses were based on protocolized evaluation and
      intervention with 6-month follow-up. Alarm symptoms were registered. Rome III
      criteria for functional pain syndromes were assigned independently. Descriptive
      statistical analyses were performed. RESULTS: In 200 patients (87 boys, mean age
      8.8 years), organic (17%), functional (40%), combined organic and functional
      (9%), spontaneous recovery (27%), and other (8%) clinical diagnoses were
      established. Alarm symptoms were found in 57.5% (organic causes 56%, functional
      causes 61%). The evaluation for Rome symptom clusters revealed symptoms of
      irritable bowel syndrome in 27%, functional dyspepsia in 15%, functional
      abdominal pain in 28%, functional abdominal pain syndrome in 14.5%, and no pain
      syndrome in 15.5%. Rome diagnoses, based on symptoms and absence of alarm
      symptoms, predicted functional clinical diagnosis with sensitivity 0.35 (95%
      confidence interval 0.27-0.43), specificity 0.60 (0.46-0.73), positive predictive
      value 0.71 (0.61-0.82), and negative predictive value of 0.24 (0.17-0.32).
      CONCLUSIONS: The Rome III criteria for abdominal pain are not specific enough to
      rule out organic causes. Alarm symptoms do not differentiate between organic and
      functional abdominal pain.

PMID- 24866785
TI  - Distinct effects of mGlu4 receptor positive allosteric modulators at
      corticostriatal vs. striatopallidal synapses may differentially contribute to
      their antiparkinsonian action.
AB  - Metabotropic glutamate 4 (mGlu4) receptor is a promising target for the treatment
      of motor deficits in Parkinson's disease (PD). This is due in part to its
      localization at key basal ganglia (BG) synapses that become hyperactive in this
      pathology, particularly striatopallidal synapses. In this context, mGlu4 receptor
      activation using either orthosteric agonists or positive allosteric modulators
      (PAMs) improves motor symptoms in rodent PD models in certain conditions.
      However, literature data show that mGlu4 receptor PAMs have no effect at
      striatopallidal GABAergic synapses (unless combined with an orthosteric agonist)
      and on the firing activity of pallidal neurons, and fail to provide significant
      motor improvement in relevant PD models. This questions the mechanistic
      hypothesis that mGlu4 receptor PAMs should act at striatopallidal synapses to
      alleviate PD motor symptoms. To shed light on this issue, we performed brain
      slice electrophysiology experiments. We show that Lu AF21934, an mGlu4 PAM small
      molecule probe-compound, was ineffective at striatopallidal synapses at all
      concentrations tested, while it significantly inhibited corticostriatal synaptic
      transmission. Similarly, Lu AF21934 did not affect electrophysiology readouts at
      striatopallidal synapses in the presence of haloperidol or in 6-hydroxydopamine
      lesioned rats. Interestingly, co-application of Lu AF21934 with a glutamate
      transporter inhibitor revealed a significant inhibitory action at striatopallidal
      synapses. Possibly, this effect could rely on increased level/permanence of
      glutamate in the synaptic cleft. Such differential efficacy of mGlu4 receptor
      PAMs at corticostriatal vs. striatopallidal synapses raises several issues
      regarding the synaptic target(s) of these drugs in the BG, and challenges the
      mechanisms by which they alleviate motor deficits in experimental PD models. 

PMID- 24866786
TI  - Prosurvival factors derived from the embryonic brain promote adult neural stem
      cell survival.
AB  - Temporally distinct populations of neural stem cells (NSCs; embryonic and adult)
      display the cardinal stem cell properties of self-renewal and multipotentiality;
      however, their relative frequency and cell kinetics vary through development and
      into old age. We asked whether changes in NSC behavior could be accounted for by
      changes in environmental signals over time. We identified a prosurvival signaling
      cascade that enhances adult-derived NSC survival using cues released from
      embryonic neurons. Specifically, we demonstrate that stromal-cell-derived factor
      1alpha (SDF-1alpha) released by embryonic neurons leads to upregulation of
      neuronal nitric oxide synthase in adult neural precursor cells. The resulting
      increase in nitric oxide leads to the upregulation of the stem cell factor (SCF)
      receptor ckit on adult NSCs (ANSCs). SCF released from embryonic neurons results
      in enhanced NSC survival. Using both in vitro and in vivo assays, we have
      demonstrated expansion of the size of the NSC pool through this pathway,
      indicating that ANSCs retain their ability to respond to embryonic-derived cues
      into adulthood. 

PMID- 24866787
TI  - ". . . How narrow the strait!". The God machine and the spirit of liberty.
AB  - This article explores the consequences of interventions to secure moral
      enhancement that are at once compulsory and inescapable and of which the subject
      will be totally unaware. These are encapsulated in an arresting example used by
      Ingmar Perrson and Julian Savulescu concerning a "God machine" capable of
      achieving at least three of these four objectives. This article demonstrates that
      the first objective--namely, moral enhancement--is impossible to achieve by these
      means and that the remaining three are neither moral nor enhancements nor
      remotely desirable. Along the way the nature of morality properly so called is
      further explored.

PMID- 24866789
TI  - Francisella tularensis LVS induction of prostaglandin biosynthesis by infected
      macrophages requires specific host phospholipases and lipid phosphatases.
AB  - Francisella tularensis induces the synthesis of prostaglandin E(2) (PGE(2)) by
      infected macrophages to alter host immune responses, thus providing a survival
      advantage to the bacterium. We previously demonstrated that PGE(2) synthesis by
      F. tularensis-infected macrophages requires cytosolic phospholipase A2 (cPLA(2)),
      cyclooxygenase 2 (COX-2), and microsomal prostaglandin E synthase 1 (mPGES1).
      During inducible PGE(2) synthesis, cPLA(2) hydrolyzes arachidonic acid (AA) from
      cellular phospholipids to be converted to PGE(2). However, in F. tularensis
      infected macrophages we observed a temporal disconnect between Ser505-cPLA(2)
      phosphorylation (a marker of activation) and PGE(2) synthesis. These results
      suggested to us that cPLA(2) is not responsible for the liberation of AA to be
      converted into PGE(2) by F. tularensis-infected macrophages. Utilizing small
      molecule inhibitors, we demonstrated that phospholipase D and diacylglycerol
      lipase were required for providing AA for PGE(2) biosynthesis. cPLA(2), on the
      other hand, was required for macrophage cytokine responses to F. tularensis. We
      also demonstrated for the first time that lipin-1 and PAP2a contribute to
      macrophage inflammation in response to F. tularensis. Our results identify both
      an alternative pathway for inducible PGE(2) synthesis and a role for lipid
      modifying enzymes in the regulation of macrophage inflammatory function.

PMID- 24866790
TI  - Proteome analysis of coinfection of epithelial cells with Filifactor alocis and
      Porphyromonas gingivalis shows modulation of pathogen and host regulatory
      pathways.
AB  - Changes in periodontal status are associated with shifts in the composition of
      the bacterial community in the periodontal pocket. The relative abundances of
      several newly recognized microbial species, including Filifactor alocis, as-yet
      unculturable organisms, and other fastidious organisms have raised questions on
      their impact on disease development. We have previously reported that the
      virulence attributes of F. alocis are enhanced in coculture with Porphyromonas
      gingivalis. We have evaluated the proteome of host cells and F. alocis during a
      polymicrobial infection. Coinfection of epithelial cells with F. alocis and P.
      gingivalis strains showed approximately 20% to 30% more proteins than a
      monoinfection. Unlike F. alocis ATCC 35896, the D-62D strain expressed more
      proteins during coculture with P. gingivalis W83 than with P. gingivalis 33277.
      Proteins designated microbial surface component-recognizing adhesion matrix
      molecules (MSCRAMMs) and cell wall anchor proteins were highly upregulated during
      the polymicrobial infection. Ultrastructural analysis of the epithelial cells
      showed formation of membrane microdomains only during coinfection. The proteome
      profile of epithelial cells showed proteins related to cytoskeletal organization
      and gene expression and epigenetic modification to be in high abundance.
      Modulation of proteins involved in apoptotic and cell signaling pathways was
      noted during coinfection. The enhanced virulence potential of F. alocis may be
      related to the differential expression levels of several putative virulence
      factors and their effects on specific host cell pathways. 

PMID- 24866791
TI  - Gastric de novo Muc13 expression and spasmolytic polypeptide-expressing
      metaplasia during Helicobacter heilmannii infection.
AB  - Helicobacter heilmannii is a zoonotic bacterium that has been associated with
      gastric disease in humans. In this study, the mRNA expression of mucins in the
      stomach of BALB/c mice was analyzed at several time points during a 1-year
      infection with this bacterium, during which gastric disease progressed in
      severity. Markers for acid production by parietal cells and mucous metaplasia
      were also examined. In the first 9 weeks postinfection, the mRNA expression of
      Muc6 was clearly upregulated in both the antrum and fundus of the stomach of H.
      heilmannii-infected mice. Interestingly, Muc13 was upregulated already at 1 day
      postinfection in the fundus of the stomach. Its expression level remained high in
      the stomach over the course of the infection. This mucin is, however, not
      expressed in a healthy stomach, and high expression of this mucin has so far only
      been described in gastric cancer. In the later stages of infection, mRNA
      expression of H(+)/K(+)-ATPase alpha/beta and KCNQ1 decreased, whereas the
      expression of Muc4, Tff2, Dmbt1, and polymeric immunoglobulin receptor (pIgR)
      increased starting at 16 weeks postinfection onwards, suggesting the existence of
      spasmolytic polypeptide-expressing metaplasia in the fundus of the stomach.
      Mucous metaplasia present in the mucosa surrounding low-grade mucosa-associated
      lymphoid tissue (MALT) lymphoma-like lesions was also histologically confirmed.
      Our findings indicate that H. heilmannii infection causes severe gastric
      pathologies and alterations in the expression pattern of gastric mucins, such as
      Muc6 and Muc13, as well as disrupting gastric homeostasis by inducing the loss of
      parietal cells, resulting in the development of mucous metaplasia. 

PMID- 24866792
TI  - Nucleoside diphosphate kinase and flagellin from Pseudomonas aeruginosa induce
      interleukin 1 expression via the Akt/NF-kappaB signaling pathways.
AB  - Inflammatory responses are a first line of host defense against a range of
      invading pathogens, consisting of the release of proinflammatory cytokines
      followed by attraction of polymorphonuclear neutrophils (PMNs) to the site of
      inflammation. Among the many virulence factors that contribute to the
      pathogenesis of infections, nucleoside diphosphate kinase (Ndk) mediates
      bacterially induced toxicity against eukaryotic cells. However, no study has
      examined how Ndk affects inflammatory responses. The present study examined the
      mechanisms by which Pseudomonas aeruginosa activates inflammatory responses upon
      infection of cells. The results showed that bacterial Ndk, with the aid of an
      additional bacterial factor, flagellin, induced expression of the proinflammatory
      cytokines interleukin-1alpha (IL-1alpha) and IL-1beta. Cytokine induction
      appeared to be dependent on the kinase activity of Ndk and was mediated via the
      NF-kappaB signaling pathway. Notably, Ndk activated the Akt signaling pathway,
      which acts upstream of NF-kappaB, as well as caspase-1, which is a key component
      of inflammasome. Thus, this study demonstrated that P. aeruginosa, through the
      combined effects of Ndk and flagellin, upregulates the expression of
      proinflammatory cytokines via the Akt/NF-kappaB signaling pathways. 

PMID- 24866793
TI  - Proteomic analysis of the Burkholderia pseudomallei type II secretome reveals
      hydrolytic enzymes, novel proteins, and the deubiquitinase TssM.
AB  - Burkholderia pseudomallei, the etiologic agent of melioidosis, is an
      opportunistic pathogen that harbors a wide array of secretion systems, including
      a type II secretion system (T2SS), three type III secretion systems (T3SS), and
      six type VI secretion systems (T6SS). The proteins exported by these systems
      provide B. pseudomallei with a growth advantage in vitro and in vivo, but
      relatively little is known about the full repertoire of exoproducts associated
      with each system. In this study, we constructed deletion mutations in gspD and
      gspE, T2SS genes encoding an outer membrane secretin and a cytoplasmic ATPase,
      respectively. The secretion profiles of B. pseudomallei MSHR668 and its T2SS
      mutants were noticeably different when analyzed by SDS-PAGE. We utilized liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) to identify proteins present
      in the supernatants of B. pseudomallei MSHR668 and B. pseudomallei DeltagspD
      grown in rich and minimal media. The MSHR668 supernatants contained 48 proteins
      that were either absent or substantially reduced in the supernatants of DeltagspD
      strains. Many of these proteins were putative hydrolytic enzymes, including 12
      proteases, two phospholipases, and a chitinase. Biochemical assays validated the
      LC-MS/MS results and demonstrated that the export of protease, phospholipase C,
      and chitinase activities is T2SS dependent. Previous studies had failed to
      identify the mechanism of secretion of TssM, a deubiquitinase that plays an
      integral role in regulating the innate immune response. Here we present evidence
      that TssM harbors an atypical signal sequence and that its secretion is mediated
      by the T2SS. This study provides the first in-depth characterization of the B.
      pseudomallei T2SS secretome. 

PMID- 24866794
TI  - CD14 influences host immune responses and alternative activation of macrophages
      during Schistosoma mansoni infection.
AB  - Antigen-presenting cell (APC) plasticity is critical for controlling inflammation
      in metabolic diseases and infections. The roles that pattern recognition
      receptors (PRRs) play in regulating APC phenotypes are just now being defined. We
      evaluated the expression of PRRs on APCs in mice infected with the helminth
      parasite Schistosoma mansoni and observed an upregulation of CD14 expression on
      macrophages. Schistosome-infected Cd14(-/-) mice showed significantly increased
      alternative activation of (M2) macrophages in the livers compared to infected
      wild-type (wt) mice. In addition, splenocytes from infected Cd14(-/-) mice
      exhibited increased production of CD4(+)-specific interleukin-4 (IL-4), IL-5, and
      IL-13 and CD4(+)Foxp3(+)IL-10(+) regulatory T cells compared to cells from
      infected wt mice. S. mansoni-infected Cd14(-/-) mice also presented with smaller
      liver egg granulomas associated with increased collagen deposition compared to
      granulomas in infected wt mice. The highest expression of CD14 was found on liver
      macrophages in infected mice. To determine if the Cd14(-/-) phenotype was in part
      due to increased M2 macrophages, we adoptively transferred wt macrophages into
      Cd14(-/-) mice and normalized the M2 and CD4(+) Th cell balance close to that
      observed in infected wt mice. Finally, we demonstrated that CD14 regulates STAT6
      activation, as Cd14(-/-) mice had increased STAT6 activation in vivo, suggesting
      that lack of CD14 impacts the IL-4Ralpha-STAT6 pathway, altering macrophage
      polarization during parasite infection. Collectively, these data identify a
      previously unrecognized role for CD14 in regulating macrophage plasticity and
      CD4(+) T cell biasing during helminth infection. 

PMID- 24866795
TI  - Complex immune cell interplay in the gamma interferon response during Toxoplasma
      gondii infection.
AB  - Toxoplasma gondii is an obligate intracellular parasite of clinical importance,
      especially in immunocompromised patients. Investigations into the immune response
      to the parasite found that T cells are the primary effector cells regulating
      gamma interferon (IFN-gamma)-mediated host resistance. However, recent studies
      have revealed a critical role for the innate immune system in mediating host
      defense independently of the T cell responses to the parasite. This body of
      knowledge is put into perspective by the unifying theme that immunity to the
      protozoan parasite requires a strong IFN-gamma host response. In the following
      review, we discuss the role of IFN-gamma-producing cells and the signals that
      regulate IFN-gamma production during T. gondii infection. 

PMID- 24866796
TI  - Nuclear factor of activated T cells regulates neutrophil recruitment, systemic
      inflammation, and T-cell dysfunction in abdominal sepsis.
AB  - The signaling mechanisms regulating neutrophil recruitment, systemic
      inflammation, and T-cell dysfunction in polymicrobial sepsis are not clear. This
      study explored the potential involvement of the calcium/calcineurin-dependent
      transcription factor, nuclear factor of activated T cells (NFAT), in abdominal
      sepsis. Cecal ligation and puncture (CLP) triggered NFAT-dependent
      transcriptional activity in the lung, spleen, liver, and aorta in NFAT-luciferase
      reporter mice. Treatment with the NFAT inhibitor A-285222 prior to CLP completely
      prevented sepsis-induced NFAT activation in all these organs. Inhibition of NFAT
      activity reduced sepsis-induced formation of CXCL1, CXCL2, and CXCL5 chemokines
      and edema as well as neutrophil infiltration in the lung. Notably, NFAT
      inhibition efficiently reduced the CLP-evoked increases in HMBG1, interleukin 6
      (IL-6), and CXCL5 levels in plasma. Moreover, administration of A-285222 restored
      sepsis-induced T-cell dysfunction, as evidenced by markedly decreased apoptosis
      and restored proliferative capacity of CD4 T cells. Along these lines, treatment
      with A-285222 restored gamma interferon (IFN-gamma) and IL-4 levels in the
      spleen, which were markedly reduced in septic mice. CLP-induced formation of
      regulatory T cells (CD4(+) CD25(+) Foxp3(+)) in the spleen was also abolished in
      A-285222-treated animals. All together, these novel findings suggest that NFAT is
      a powerful regulator of pathological inflammation and T-cell immune dysfunction
      in abdominal sepsis. Thus, our data suggest that NFAT signaling might be a useful
      target to protect against respiratory failure and immunosuppression in patients
      with sepsis. 

PMID- 24866797
TI  - Development and characterization of a long-term murine model of Streptococcus
      pneumoniae infection of the lower airways.
AB  - Chronic obstructive pulmonary disease (COPD) is characterized by long periods of
      stable symptoms, but exacerbations occur, which result in a permanent worsening
      of symptoms. Previous studies have shown a link between bacterial colonization of
      the lower airways of COPD sufferers and an increase in exacerbation frequency.
      One of the most frequent bacterial colonizers is Streptococcus pneumoniae. To
      mimic this aspect of COPD, a murine model of low-level pneumococcal colonization
      in the lung has been developed, in which S. pneumoniae persisted in the lungs for
      at least 28 days. From day 14 postinfection, bacterial numbers remained constant
      until at least 28 days postinfection, and animals showed no outward signs of
      disease. The bacterial presence correlated with a low-level inflammatory response
      that was localized to small foci across the left and inferior lobes of the lung.
      The cellular response was predominantly monocytic, and focal fibroplasia was
      observed at the airway transitional zones. Physiological changes in the lungs
      were investigated with a Forced Maneuvers system. This new model provides a means
      of study of a long-term pulmonary infection with a human pathogen in a rodent
      system. This is an excellent tool for the development of future models that mimic
      complex respiratory diseases such as COPD and asthma. 

PMID- 24866798
TI  - Development of an ex vivo porcine lung model for studying growth, virulence, and
      signaling of Pseudomonas aeruginosa.
AB  - Research into chronic infection by bacterial pathogens, such as Pseudomonas
      aeruginosa, uses various in vitro and live host models. While these have
      increased our understanding of pathogen growth, virulence, and evolution, each
      model has certain limitations. In vitro models cannot recapitulate the complex
      spatial structure of host organs, while experiments on live hosts are limited in
      terms of sample size and infection duration for ethical reasons; live mammal
      models also require specialized facilities which are costly to run. To address
      this, we have developed an ex vivo pig lung (EVPL) model for quantifying
      Pseudomonas aeruginosa growth, quorum sensing (QS), virulence factor production,
      and tissue damage in an environment that mimics a chronically infected cystic
      fibrosis (CF) lung. In a first test of our model, we show that lasR mutants,
      which do not respond to 3-oxo-C(12)-homoserine lactone (HSL)-mediated QS, exhibit
      reduced virulence factor production in EVPL. We also show that lasR mutants grow
      as well as or better than a corresponding wild-type strain in EVPL. lasR mutants
      frequently and repeatedly arise during chronic CF lung infection, but the
      evolutionary forces governing their appearance and spread are not clear. Our data
      are not consistent with the hypothesis that lasR mutants act as social "cheats"
      in the lung; rather, our results support the hypothesis that lasR mutants are
      more adapted to the lung environment. More generally, this model will facilitate
      improved studies of microbial disease, especially studies of how cells of the
      same and different species interact in polymicrobial infections in a spatially
      structured environment.

PMID- 24866799
TI  - The psmalpha locus regulates production of Staphylococcus aureus alpha-toxin
      during infection.
AB  - Staphylococcus aureus is a leading cause of human bacterial infection, causing a
      wide spectrum of disease ranging from skin and soft tissue infections to life
      threatening pneumonia and sepsis. S. aureus toxins play an essential role in
      disease pathogenesis, contributing to both immunomodulation and host tissue
      injury. Prominent among these toxins are the membrane-active pore-forming
      cytolysin alpha-toxin (Hla) and the amphipathic alpha-helical phenol-soluble
      modulin (PSM) peptides. As deletion of either the hla or psm locus leads to a
      phenotypically similar virulence defect in skin and soft tissue infection, we
      sought to determine the relative contribution of each locus to disease
      pathogenesis. Here we show that production of Hla can be modulated by PSM
      expression. An S. aureus mutant lacking PSM expression exhibits a transcriptional
      delay in hla mRNA production and therefore fails to secrete normal levels of Hla
      at early phases of growth. This leads to attenuation of virulence in vitro and in
      murine skin and lung models of infection, correlating with reduced recovery of
      Hla from host tissues. Production of Hla and restoration of staphylococcal
      virulence can be achieved in the psm mutant by plasmid-driven overexpression of
      hla. Our study suggests the coordinated action of Hla and PSMs in host tissue
      during early pathogenesis, confirming a major role for Hla in epithelial injury
      during S. aureus infection. These findings highlight the possibility that
      therapeutics targeting PSM production may simultaneously prevent Hla-mediated
      tissue injury. 

PMID- 24866800
TI  - Giardia muris infection in mice is associated with a protective interleukin 17A
      response and induction of peroxisome proliferator-activated receptor alpha.
AB  - The protozoan parasite Giardia duodenalis (Giardia lamblia) is one of the most
      commonly found intestinal pathogens in mammals, including humans. In the current
      study, a Giardia muris-mouse model was used to analyze cytokine transcription
      patterns and histological changes in intestinal tissue at different time points
      during infection in C57BL/6 mice. Since earlier work revealed the upregulation of
      peroxisome proliferator-activated receptors (PPARs) in Giardia-infected calves, a
      second aim was to investigate the potential activation of PPARs in the intestines
      of infected mice. The most important observation in all mice was a strong
      upregulation of il17a starting around 1 week postinfection. The significance of
      interleukin 17A (IL-17A) in orchestrating a protective immune response was
      further demonstrated in an infection trial or experiment using IL-17 receptor A
      (IL-17RA) knockout (KO) mice: whereas in wild-type (WT) mice, cyst secretion
      dropped significantly after 3 weeks of infection, the IL-17RA KO mice were unable
      to clear the infection. Analysis of the intestinal response further indicated
      peroxisome proliferator-activated receptor alpha (PPARalpha) induction soon after
      the initial contact with the parasite, as characterized by the transcriptional
      upregulation of ppara itself and several downstream target genes such as pltp and
      cpt1. Overall, PPARalpha did not seem to have any influence on the immune
      response against G. muris, since PPARalpha KO animals expressed il-17a and could
      clear the infection similar to WT controls. In conclusion, this study shows for
      the first time the importance of IL-17 production in the clearance of a G. muris
      infection together with an early induction of PPARalpha. The effect of the
      latter, however, is still unclear. 

PMID- 24866801
TI  - Deep sequencing analysis reveals temporal microbiota changes associated with
      development of bovine digital dermatitis.
AB  - Bovine digital dermatitis (DD) is a leading cause of lameness in dairy cattle
      throughout the world. Despite 35 years of research, the definitive etiologic
      agent associated with the disease process is still unknown. Previous studies have
      demonstrated that multiple bacterial species are associated with lesions, with
      spirochetes being the most reliably identified organism. This study details the
      deep sequencing-based metagenomic evaluation of 48 staged DD biopsy specimens
      collected during a 3-year longitudinal study of disease progression. Over 175
      million sequences were evaluated by utilizing both shotgun and 16S metagenomic
      techniques. Based on the shotgun sequencing results, there was no evidence of a
      fungal or DNA viral etiology. The bacterial microbiota of biopsy specimens
      progresses through a systematic series of changes that correlate with the novel
      morphological lesion scoring system developed as part of this project. This
      scoring system was validated, as the microbiota of each stage was statistically
      significantly different from those of other stages (P < 0.001). The microbiota of
      control biopsy specimens were the most diverse and became less diverse as lesions
      developed. Although Treponema spp. predominated in the advanced lesions, they
      were in relatively low abundance in the newly described early lesions that are
      associated with the initiation of the disease process. The consortium of
      Treponema spp. identified at the onset of disease changes considerably as the
      lesions progress through the morphological stages identified. The results of this
      study support the hypothesis that DD is a polybacterial disease process and
      provide unique insights into the temporal changes in bacterial populations
      throughout lesion development. 

PMID- 24866802
TI  - The periodontal pathogen Porphyromonas gingivalis induces expression of
      transposases and cell death of Streptococcus mitis in a biofilm model.
AB  - Oral microbial communities are extremely complex biofilms with high numbers of
      bacterial species interacting with each other (and the host) to maintain
      homeostasis of the system. Disturbance in the oral microbiome homeostasis can
      lead to either caries or periodontitis, two of the most common human diseases.
      Periodontitis is a polymicrobial disease caused by the coordinated action of a
      complex microbial community, which results in inflammation of tissues that
      support the teeth. It is the most common cause of tooth loss among adults in the
      United States, and recent studies have suggested that it may increase the risk
      for systemic conditions such as cardiovascular diseases. In a recent series of
      papers, Hajishengallis and coworkers proposed the idea of the "keystone-pathogen"
      where low-abundance microbial pathogens (Porphyromonas gingivalis) can
      orchestrate inflammatory disease by turning a benign microbial community into a
      dysbiotic one. The exact mechanisms by which these pathogens reorganize the
      healthy oral microbiome are still unknown. In the present manuscript, we present
      results demonstrating that P. gingivalis induces S. mitis death and DNA
      fragmentation in an in vitro biofilm system. Moreover, we report here the
      induction of expression of multiple transposases in a Streptococcus mitis biofilm
      when the periodontopathogen P. gingivalis is present. Based on these results, we
      hypothesize that P. gingivalis induces S. mitis cell death by an unknown
      mechanism, shaping the oral microbiome to its advantage. 

PMID- 24866803
TI  - The Borrelia hermsii factor H binding protein FhbA is not required for
      infectivity in mice or for resistance to human complement in vitro.
AB  - The primary causative agent of tick-borne relapsing fever in North America is
      Borrelia hermsii. It has been hypothesized that B. hermsii evades complement
      mediated destruction by binding factor H (FH), a host-derived negative regulator
      of complement. In vitro, B. hermsii produces a single FH binding protein
      designated FhbA (FH binding protein A). The properties and ligand binding
      activity of FhbA suggest that it plays multiple roles in pathogenesis. It binds
      plasminogen and has been identified as a significant target of a B1b B cell
      mediated IgM response in mice. FhbA has also been explored as a potential
      diagnostic antigen for B. hermsii infection in humans. The ability to test the
      hypothesis that FhbA is a critical virulence factor in vivo has been hampered by
      the lack of well-developed systems for the genetic manipulation of the relapsing
      fever spirochetes. In this report, we have successfully generated a B. hermsii
      fhbA deletion mutant (the B. hermsii YORDeltafhbA strain) through allelic
      exchange mutagenesis. Deletion of fhbA abolished FH binding by the YORDeltafhbA
      strain and eliminated cleavage of C3b on the cell surface. However, the
      YORDeltafhbA strain remained infectious in mice and retained resistance to
      killing in vitro by human complement. Collectively, these results indicate that
      B. hermsii employs an FhbA/FH-independent mechanism of complement evasion that
      allows for resistance to killing by human complement and persistence in mice. 

PMID- 24866804
TI  - Plasmid CDS5 influences infectivity and virulence in a mouse model of Chlamydia
      trachomatis urogenital infection.
AB  - The native plasmid of both Chlamydia muridarum and Chlamydia trachomatis has been
      shown to control virulence and infectivity in mice and in lower primates. We
      recently described the development of a plasmid-based genetic transformation
      protocol for Chlamydia trachomatis that for the first time provides a platform
      for the molecular dissection of the function of the chlamydial plasmid and its
      individual genes or coding sequences (CDS). In the present study, we transformed
      a plasmid-free lymphogranuloma venereum isolate of C. trachomatis, serovar L2,
      with either the original shuttle vector (pGFP::SW2) or a derivative of pGFP::SW2
      carrying a deletion of the plasmid CDS5 gene (pCDS5KO). Female mice were
      inoculated with these strains either intravaginally or transcervically. We found
      that transformation of the plasmid-free isolate with the intact pGFP::SW2 vector
      significantly enhanced infectivity and induction of host inflammatory responses
      compared to the plasmid-free parental isolate. Transformation with pCDS5KO
      resulted in infection courses and inflammatory responses not significantly
      different from those observed in mice infected with the plasmid-free isolate.
      These results indicate a critical role of plasmid CDS5 in in vivo fitness and in
      induction of inflammatory responses. To our knowledge, these are the first in
      vivo observations ascribing infectivity and virulence to a specific plasmid gene.

PMID- 24866805
TI  - Host defense peptide resistance contributes to colonization and maximal
      intestinal pathology by Crohn's disease-associated adherent-invasive Escherichia
      coli.
AB  - Host defense peptides secreted by colonocytes and Paneth cells play a key role in
      innate host defenses in the gut. In Crohn's disease, the burden of tissue
      associated Escherichia coli commonly increases at epithelial surfaces where host
      defense peptides concentrate, suggesting that this bacterial population might
      actively resist this mechanism of bacterial killing. Adherent-invasive E. coli
      (AIEC) is associated with Crohn's disease; however, the colonization determinants
      of AIEC in the inflamed gut are undefined. Here, we establish that host defense
      peptide resistance contributes to host colonization by Crohn's-associated AIEC.
      We identified a plasmid-encoded genomic island (called PI-6) in AIEC strain
      NRG857c that confers high-level resistance to alpha-helical cationic peptides and
      alpha- and beta-defensins. Deletion of PI-6 sensitized strain NRG857c to these
      host defense molecules, reduced its competitive fitness in a mouse model of
      infection, and attenuated its ability to induce cecal pathology. This phenotype
      is due to two genes in PI-6, arlA, which encodes a Mig-14 family protein
      implicated in defensin resistance, and arlC, an OmpT family outer membrane
      protease. Implicit in these findings are new bacterial targets whose inhibition
      might limit AIEC burden and disease in the gut. 

PMID- 24866808
TI  - The facet-dependent enhanced catalytic activity of Pd nanocrystals.
AB  - A systematic study of heterogeneous Buchwald-Hartwig amination using shape
      controlled Pd nanocrystals with distinctly different surface facets is presented.

PMID- 24866807
TI  - Burkholderia pseudomallei capsular polysaccharide conjugates provide protection
      against acute melioidosis.
AB  - Burkholderia pseudomallei, the etiologic agent of melioidosis, is a CDC tier 1
      select agent that causes severe disease in both humans and animals. Diagnosis and
      treatment of melioidosis can be challenging, and in the absence of optimal
      chemotherapeutic intervention, acute disease is frequently fatal. Melioidosis is
      an emerging infectious disease for which there are currently no licensed
      vaccines. Due to the potential malicious use of B. pseudomallei as well as its
      impact on public health in regions where the disease is endemic, there is
      significant interest in developing vaccines for immunization against this
      disease. In the present study, type A O-polysaccharide (OPS) and manno-heptose
      capsular polysaccharide (CPS) antigens were isolated from nonpathogenic, select
      agent-excluded strains of B. pseudomallei and covalently linked to carrier
      proteins. By using these conjugates (OPS2B1 and CPS2B1, respectively), it was
      shown that although high-titer IgG responses against the OPS or CPS component of
      the glycoconjugates could be raised in BALB/c mice, only those animals immunized
      with CPS2B1 were protected against intraperitoneal challenge with B.
      pseudomallei. Extending upon these studies, it was also demonstrated that when
      the mice were immunized with a combination of CPS2B1 and recombinant B.
      pseudomallei LolC, rather than with CPS2B1 or LolC individually, they exhibited
      higher survival rates when challenged with a lethal dose of B. pseudomallei.
      Collectively, these results suggest that CPS-based glycoconjugates are promising
      candidates for the development of subunit vaccines for immunization against
      melioidosis. 

PMID- 24866806
TI  - Inflammatory effects of Edwardsiella ictaluri lipopolysaccharide modifications in
      catfish gut.
AB  - Bacterial lipopolysaccharides (LPS) are structural components of the outer
      membranes of Gram-negative bacteria and also are potent inducers of inflammation
      in mammals. Higher vertebrates are extremely sensitive to LPS, but lower
      vertebrates, like fish, are resistant to their systemic toxic effects. However,
      the effects of LPS on the fish intestinal mucosa remain unknown. Edwardsiella
      ictaluri is a primitive member of the Enterobacteriaceae family that causes
      enteric septicemia in channel catfish (Ictalurus punctatus). E. ictaluri infects
      and colonizes deep lymphoid tissues upon oral or immersion infection. Both gut
      and olfactory organs are the primary sites of invasion. At the systemic level, E.
      ictaluri pathogenesis is relatively well characterized, but our knowledge about
      E. ictaluri intestinal interaction is limited. Recently, we observed that E.
      ictaluri oligo-polysaccharide (O-PS) LPS mutants have differential effects on the
      intestinal epithelia of orally inoculated catfish. Here we evaluate the effects
      of E. ictaluri O-PS LPS mutants by using a novel catfish intestinal loop model
      and compare it to the rabbit ileal loop model inoculated with Salmonella enterica
      serovar Typhimurium LPS. We found evident differences in rabbit ileal loop and
      catfish ileal loop responses to E. ictaluri and S. Typhimurium LPS. We determined
      that catfish respond to E. ictaluri LPS but not to S. Typhimurium LPS. We also
      determined that E. ictaluri inhibits cytokine production and induces disruption
      of the intestinal fish epithelia in an O-PS-dependent fashion. The E. ictaluri
      wild type and DeltawibT LPS mutant caused intestinal tissue damage and inhibited
      proinflammatory cytokine synthesis, in contrast to E. ictaluri Deltagne and
      Deltaugd LPS mutants. We concluded that the E. ictaluri O-PS subunits play a
      major role during pathogenesis, since they influence the recognition of the LPS
      by the intestinal mucosal immune system of the catfish. The LPS structure of E.
      ictaluri mutants is needed to understand the mechanism of interaction. 

PMID- 24866809
TI  - Aortocaval fistula.

PMID- 24866810
TI  - Uric acid and cardiac performance.

PMID- 24866811
TI  - Live-cell SERS endoscopy using plasmonic nanowire waveguides.
AB  - Live-cell surface-enhanced Raman spectroscopy (SERS) endoscopy is developed by
      using plasmonic nanowire waveguides as endoscopic probes. It is demonstrated that
      the probe insertion does not stress the cell. Opposed to conventional SERS
      endoscopy, with excitation at the hotspot within the cell, the remote excitation
      method yields low-background SERS spectra from specific cell compartments with
      minimal associated photodamage. 

PMID- 24866814
TI  - Fusion and fission inhibited by the same mechanism in electrostatically charged
      surfactant micelles.
AB  - This paper revises the general idea about the role of intermicellar and
      intramiceller interactions in inhibiting fusion of self-assembled surfactant
      micelles. Fusion and fission of micelles are usually thought to be limited by
      different mechanisms. While fission is accepted to be controlled by surface
      instabilities (intramicellar interactions), fusion is commonly thought to be rate
      limited by the barrier to the close approach between two micelles due to the
      steric or Coulombic repulsions (intramicellar interactions). Here we describe the
      role of electrostatic repulsions in inhibiting fusion and fission kinetics in
      self-assembled micelles. We use stopped flow-fluorescence technique with
      hydrophobic pyrene to quantify fusion and fission in ionic/nonionic mixed
      micelles (Triton X-100/SDS). We show that the fusion and fission rates decrease
      with the same tendency with increasing the fraction of the ionic charges, while
      their ratio remains constant. Our results are interpreted to mean that, in
      slightly charged micelles, fusion shares the same limiting step with fission,
      which most likely involves surface instabilities and intramiceller interactions. 

PMID- 24866813
TI  - Taurine supplementation increases K(ATP) channel protein content, improving Ca2+
      handling and insulin secretion in islets from malnourished mice fed on a high-fat
      diet.
AB  - Pancreatic beta-cells are highly sensitive to suboptimal or excess nutrients, as
      occurs in protein-malnutrition and obesity. Taurine (Tau) improves insulin
      secretion in response to nutrients and depolarizing agents. Here, we assessed the
      expression and function of Cav and KATP channels in islets from malnourished mice
      fed on a high-fat diet (HFD) and supplemented with Tau. Weaned mice received a
      normal (C) or a low-protein diet (R) for 6 weeks. Half of each group were fed a
      HFD for 8 weeks without (CH, RH) or with 5% Tau since weaning (CHT, RHT).
      Isolated islets from R mice showed lower insulin release with glucose and
      depolarizing stimuli. In CH islets, insulin secretion was increased and this was
      associated with enhanced KATP inhibition and Cav activity. RH islets secreted
      less insulin at high K(+) concentration and showed enhanced KATP activity. Tau
      supplementation normalized K(+)-induced secretion and enhanced glucose-induced
      Ca(2+) influx in RHT islets. R islets presented lower Ca(2+) influx in response
      to tolbutamide, and higher protein content and activity of the Kir6.2 subunit of
      the KATP. Tau increased the protein content of the alpha1.2 subunit of the Cav
      channels and the SNARE proteins SNAP-25 and Synt-1 in CHT islets, whereas in RHT,
      Kir6.2 and Synt-1 proteins were increased. In conclusion, impaired islet function
      in R islets is related to higher content and activity of the KATP channels. Tau
      treatment enhanced RHT islet secretory capacity by improving the protein
      expression and inhibition of the KATP channels and enhancing Synt-1 islet
      content.

PMID- 24866815
TI  - Intraoperative electrocorticography-guided microsurgical management for patients
      with onset of supratentorial neoplasms manifesting as epilepsy: a review of 65
      cases.
AB  - AIM: We reviewed the surgical procedures guided by intraoperative
      electrocorticography and outcome of 65 patients with onset of supratentorial
      neoplasms manifesting as epilepsy. METHOD: Clinical data were obtained for 65
      patients with supratentorial neoplasms who received surgery, with the aid of
      intraoperative electrocorticography to screen epileptogenic foci before and after
      removal of neoplasms, and depth electrodes when needed. According to
      electrocorticography findings, appropriate surgical procedures were performed to
      treat the epileptogenic foci. In the control group, 72 patients received simple
      lesionectomy. Postoperative seizure outcomes were documented and analysed
      retrospectively. RESULTS: In the case group, 33 patients received lesionectomy
      only, while the other 32 patients underwent intraoperative electrocorticography
      guided tailored epilepsy surgery. In total, 57 patients (87.7%) in the case group
      and 38 patients (52.8%) in the control group were seizure-free (Engel Class I).
      Comparing outcomes of patients with temporal lesions between the two groups,
      80.0% patients (12/15) in the case group and 20.0% (3/15) in the control group
      were seizure-free. Furthermore, comparing the seizure outcomes of patients who
      finally underwent tailored epilepsy surgery and simple lesionectomy (33 after
      electrocorticography and 72 without electrocorticography), intraoperative
      electrocorticography-guided tailored epilepsy surgery demonstrated superiority
      over lesionectomy (Engel Class I; 87.5% vs. 63.8%, respectively). CONCLUSIONS:
      Electrocorticography plays an important role in the localisation of epileptogenic
      foci and evaluation of the effects of microsurgical procedures intraoperatively.
      Isolated lesionectomy is not usually sufficient for better postoperative seizure
      outcome. In addition, for patients with temporal tumours, especially in the non
      dominant hemisphere, a more aggressive strategy, such as an anterior temporal
      lobectomy, is recommended.

PMID- 24866812
TI  - Dietary supplement use among participants of a databank and biorepository at a
      comprehensive cancer centre.
AB  - OBJECTIVE: We assessed the prevalence, patterns and predictors of dietary
      supplement use among participants of the databank and biorepository (DBBR) at a
      comprehensive cancer centre in western New York. DESIGN: Archived epidemiological
      questionnaire data were obtained from the DBBR at Roswell Park Cancer Institute.
      Descriptive statistics and logistic regression explored the prevalence, patterns
      and predictors of lifetime use of four common supplements (multivitamins, vitamin
      C, vitamin E and calcium) and use of multivitamins, sixteen single
      vitamins/minerals and eighteen herbal/specialty supplements within the previous
      10 years. SETTING: Western New York, USA. SUBJECTS: DBBR participants (n 8096)
      enrolled between December 2003 and July 2012 were included in these analyses:
      66.9 % (n 5418) with cancer, 65.6 % (n 5309) women, mean age for patients v.
      cancer-free controls 59.9 (SD 12.6) years and 50.7 (SD 15.4) years, respectively.
      RESULTS: Overall, 54.4 % of DBBR participants reported lifetime use of one or
      more supplements and 63.1 % reported use of one or more supplements within the
      previous 10 years (excluding multivitamins). Multivitamin use was high in this
      sample (lifetime: 64.1 %; 10 years: 71.3 %; current: 51.8 %). Supplementation was
      higher among cancer-free controls than cancer patients. Vitamin C, calcium and
      fish oil were the most common single vitamin, mineral and specialty product,
      respectively. CONCLUSIONS: A consistently high and increasing proportion of
      dietary supplement use over time remains clear. Supplementation is prevalent
      among cancer patients and may even be higher than predicted in cancer-free
      individuals. Further studies should assess the safety and efficacy of specific
      supplements in reducing disease risk.

PMID- 24866817
TI  - The gap between the physiological and therapeutic roles of mesenchymal stem
      cells.
AB  - Several investigators have cultivated marrow stromal cells and have identified a
      population of mesenchymal stem cells (MSCs). These cells expand extensively in
      vitro and exhibit multilineage differentiation potential. The lack of MSC
      specific markers impedes identification of MSC functions. Further in vivo studies
      of these cells may elucidate the nature of MSCs. Although the nature of MSCs
      remains unclear, nonclonal stromal cultures are used as a source of putative MSCs
      for therapeutic purposes. Preclinical studies and clinical trials assumed that
      transplanted MSCs exert their effects through their differentiation properties or
      through the release of molecules that restore tissue functions and modulate
      immune cells. These studies reported contradictory results and failed to meet
      expectations. Thus, it is important to note that current protocols for MSC
      therapy are primarily based on the use of in vitro expanded nonclonal MSCs.
      Clearly defining the physiological features of in situ MSCs and the in vitro and
      in vivo properties of nonclonal cultures of stromal cells, which are often
      misidentified as pure stem cell cultures, may explain the reported failures of
      MSC therapy. This review will address these issues. 

PMID- 24866816
TI  - Binding affinity and cooperativity control U2B"/snRNA/U2A' RNP formation.
AB  - The U1A and U2B" proteins are components of the U1 and U2 snRNPs, respectively,
      where they bind to snRNA stemloops. While localization of U1A and U2B" to their
      respective snRNP is a well-known phenomenon, binding of U2B" to U2 snRNA is
      typically thought to be accompanied by the U2A' protein. The molecular mechanisms
      that lead to formation of the RNA/U2B"/U2A' complex and its localization to the
      U2 snRNP are investigated here, using a combination of in vitro RNA-protein and
      protein-protein fluorescence and isothermal titration calorimetry binding
      experiments. We find that U2A' protein binds to U2B" with nanomolar affinity but
      binds to U1A with only micromolar affinity. In addition, there is RNA-dependent
      cooperativity (linkage) between protein-protein and protein-RNA binding. The
      unique combination of tight binding and cooperativity ensures that the U2A'/U2B"
      complex is partitioned only to the U2 snRNP.

PMID- 24866818
TI  - Social anxiety, submissiveness, and shame in men and women: a moderated mediation
      analysis.
AB  - OBJECTIVES: Research suggests a positive relationship between social anxiety and
      shame; however, few studies have examined this relationship or potential
      mechanisms. Common behaviours of persons with social anxiety disorder (SAD), such
      as submissive behaviours, may be more consistent with societal expectations of
      women than men and therefore more likely to be associated with shame in socially
      anxious men than women. We examined the hypothesis that submissive behaviours
      would mediate the relationship between social anxiety and shame in men, but not
      in women, with SAD. DESIGN: Moderated mediation was examined in a cross-sectional
      dataset. Gender was modeled to moderate the paths from social anxiety to
      submissive behaviours and from submissive behaviours to shame. We also examined
      an alternative model of the relationships among these variables and the potential
      contributory role of depression. METHODS: Men (n = 48) and women (n = 40) with
      SAD completed the Social Interaction Anxiety Scale, Submissive Behaviour Scale,
      Internalized Shame Scale, and Beck Depression Inventory. RESULTS: Analyses
      supported the hypothesized model. The relationship between submissive behaviours
      and shame was greater in men than women with SAD; the relationship between social
      anxiety and submissive behaviours was not. Controlling for depression, moderation
      remained evident although diminished. Results for the comparison model did not
      support gender moderation. CONCLUSIONS: Submissive behaviours mediated the
      relationship between social anxiety and shame in men, but not women, with SAD.
      These findings provide preliminary evidence for a model of shame in SAD and may
      help to further elucidate specific features of SAD that differ between men and
      women. PRACTITIONER POINTS: Although researchers have argued that the display of
      submissive behaviours might allow the socially anxious individual to limit or
      prevent attacks on the self, our results suggest that there are greater costs,
      with regard to feelings of shame, associated with such behaviours for men. In men
      with SAD, the greater shame associated with submissive behaviours can be
      understood when considering that socially anxious individuals appear to be
      particularly concerned with concealing aspects of the self believed to violate
      perceived societal norms and that traditional masculine gender roles revolve
      around the theme of dominance. Because the study was conducted in individuals
      with SAD, it is possible that the restricted range of social anxiety severity may
      have precluded the observation of gender differences in the relationship between
      social anxiety and submissive behaviour. Measures were administered in a cross
      sectional design, which limits potential inferences of causality.

PMID- 24866820
TI  - Anion-exchange and anthracene-encapsulation within copper(II) and manganese(II)
      triazole metal-organic confined space in a single crystal-to-single crystal
      transformation fashion.
AB  - A new multidentate ligand 1-(9-(1H-1,2,4-triazol-1-yl)anthracen-10-yl)-1H-1,2,4
      triazole (tatrz) was designed and synthesized. Using tatrz as a building block,
      three novel coordination frameworks, namely, {[Cu(tatrz)2(NO3)2].(CH3OH).4H2O}n
      (1), {[Cu(tatrz)2(H2O)2](BF4)2}n (2), and [Mn(tatrz)2(SCN)2(CH3OH)].2H2O (3) can
      be isolated. Anion-exchange experiment indicates that NO3(-) anions in the two
      dimensional (2D) copper framework of 1 can be completely exchanged by ClO4(-) in
      an irreversible single crystal-to-single crystal (SC-SC) transformation fashion,
      as evidenced by the anion-exchange products of {[Cu(tatrz)2(H2O)2](ClO4)2.4CH3OH}
      (1a). Further, if 1a was employed as a precursor in N,N-dimethylformamide (DMF),
      an isomorphic solvate of {[Cu(tatrz)2(DMF)2](ClO4)2.2H2O}n (1b) can be generated
      during the reversible dynamic transformation process. When 1 was immersed in
      CH3OH, a distinct 2D layer {[Cu(tatrz)2(NO3)2].4.4CH3OH.0.6H2O}n (1c) was
      isolated. Interestingly, the solvent-exchange conversion is also invertible
      between 1 and 1c, which exhibits spongelike dynamic behavior with retention of
      crystalline integrity. If the 2-fold interpenetrating three-dimensional (3D)
      framework 2 is selected, it can be transformed into another 2-fold
      interpenetrating 3D framework {[Cu(tatrz)2(H2O)2](ClO4)2.5.56H2O}n (2a) in a
      reversible SC-SC transformation fashion. However, when the light yellow crystals
      of mononuclear complex 3 were exposed to trichloromethane containing aromatic
      organic anthracene (atan), through our careful observation, the crystals of 3
      were dissolved and reassembled into dark brown crystals of 2D crystalline
      coordination framework {[Mn(tatrz)2(SCN)2].(atan)}n (3a). X-ray diffraction
      revealed that in 3a, atan acting as an organic template was encapsulated in the
      confined space of the 2D grid. Luminescent measurements illustrate that 3a is the
      first report of multidimensional polymers based on triazole derivatives as
      luminescent probes of Mg(2+). 

PMID- 24866819
TI  - Global warming favours light-coloured insects in Europe.
AB  - Associations between biological traits of animals and climate are well documented
      by physiological and local-scale studies. However, whether an ecophysiological
      phenomenon can affect large-scale biogeographical patterns of insects is largely
      unknown. Insects absorb energy from the sun to become mobile, and their
      colouration varies depending on the prevailing climate where they live. Here we
      show, using data of 473 European butterfly and dragonfly species, that dark
      coloured insect species are favoured in cooler climates and light-coloured
      species in warmer climates. By comparing distribution maps of dragonflies from
      1988 and 2006, we provide support for a mechanistic link between climate,
      functional traits and species that affects geographical distributions even at
      continental scales. Our results constitute a foundation for better forecasting
      the effect of climate change on many insect groups. 

PMID- 24866821
TI  - Two-photon-responsive supramolecular hydrogel for controlling materials motion in
      micrometer space.
AB  - Spatiotemporal control of fluidity inside a soft matrix by external stimuli
      allows real-time manipulation of nano/micromaterials. In this study, we report a
      two-photon-responsive peptide-based supramolecular hydrogel, the fluidity of
      which was dramatically controlled with high spatial resolution (10 MUm*10 MUm*10
      MUm). The off-on switching of the Brownian motion of nanobeads and chemotaxis of
      bacteria by two-photon excitation was successfully demonstrated. 

PMID- 24866823
TI  - Recurrent inhibition in motor systems, a comparative analysis.
AB  - The review proposes a comparison between recurrent inhibition in motor systems of
      vertebrates and the leech nervous system, where a detailed cellular and
      functional analysis has been accomplished. A comparative study shows that
      recurrent inhibition is a conserved property in motor systems of phylogenetically
      distant species. Recurrent inhibition has been extensively characterized in the
      spinal cord of mammals, where Renshaw cells receive excitatory synaptic inputs
      from motoneurons (MNs) and, in turn, exert an inhibitory effect on the MNs. In
      the leech, a recurrent inhibitory circuit has been described, centered around a
      pair of nonspiking (NS) neurons. NS are linked to every excitatory MN through
      rectifying electrical junctions. And, in addition, the MNs are linked to the NS
      neurons through hyperpolarizing chemical synapses. Functional analysis of this
      leech circuit showed that heteronymous MNs in the leech are electrically coupled
      and this coupling is modulated by the membrane potential of NS neurons. Like
      Renshaw cells, the membrane potential of NS neurons oscillates in phase with
      rhythmic motor patterns. Functional analysis performed in the leech shows that NS
      influences the activity of MNs in the course of crawling suggesting that the
      recurrent inhibitory circuit modulates the motor performance. 

PMID- 24866824
TI  - Surgery for a giant arteriovenous malformation without motor deterioration:
      preoperative transcranial magnetic stimulation in a non-cooperative patient.
AB  - Transcranial magnetic stimulation (TMS) is a noninvasive activation method that
      is increasingly used for motor mapping. Preoperative functional mapping in
      vascular surgery is not routinely performed; however, in cases of high-grade
      arteriovenous malformations (AVMs), it could play a role in preoperative decision
      making. A 16-year-old male was suffering from a giant, right-sided insular,
      Spetzler-Martin Grade V AVM. This patient's history included 3 hemorrhagic
      strokes in the past 3 years, resulting in Medical Research Council Grade 2-3
      (proximal) and 2-4 (distal) paresis of the left side of the body and
      hydrocephalus requiring a ventriculoperitoneal shunt. Preoperative TMS showed
      absent contralateral innervation of the remaining left-sided motor functions.
      Subsequently, the AVM was completely resected without any postoperative increase
      of the left-sided paresis. This case shows that TMS can support decision making
      in AVM treatment by mapping motor functions. 

PMID- 24866825
TI  - Oncoprotein ubiquitylation: dimers, degrons, and degradation.

PMID- 24866826
TI  - The impact of stent design on the structural mechanics of the crossing Y-stent:
      an in vitro study.
AB  - INTRODUCTION: Crossing Y-stent technique is a valid option for coiling wide
      necked bifurcation aneurysms. Two main designs of stents, the closed- (CCS) and
      open-cell (OCS), are used in combination for a crossing Y-construct. This in
      vitro study was conducted to assess the mechanical characteristics of each stent
      combination and to suggest an optimal combination for clinical practice. METHODS:
      The Enterprise and the Neuroform3 stents were used as closed-cell and open-cell
      stents, respectively. Four different Y-stent combinations; double CCSs (CCS-CCS;
      Enterprise-Enterprise), OCS followed by CCS (OCS-CCS; Neuroform-Enterprise), CCS
      followed by OCS (CCS-OCS; Enterprise-Neuroform), and double OCSs (OCS-OCS;
      Neuroform-Neuroform) were tested in a bifurcation aneurysm model. Images of the
      model were obtained by digital subtraction angiography (DSA), and morphological
      changes of Y-constructs caused by interaction between stents were compared.
      RESULTS: Double OCSs showed the best stent apposition to model branches and no
      collapse of the second stent at the intersection, whereas Y-stent combinations
      using a CCS as the second stent showed tubular collapse of the second stent at
      the crossing point. These combinations revealed unsatisfactory apposition to the
      model branch in which the second stent was deployed. Most narrowing of the second
      stent was noted in the double CCSs construct, which resulted in poorest stent
      apposition. CONCLUSION: Based on a simple in vitro experiment, we suggest that
      double OCSs Y-construct is optimal for achieving best stent-wall apposition.
      Furthermore, our findings suggest that Y-stent combinations utilizing a CCS as
      the second stent may increase the risk of thromboembolic complications due to
      poor stent-wall apposition.

PMID- 24866827
TI  - FLAIR vascular hyperintensities and dynamic 4D angiograms for the estimation of
      collateral blood flow in posterior circulation occlusion.
AB  - INTRODUCTION: The objectives of this paper are to assess collateral blood flow in
      posterior circulation occlusion by MRI-based approaches (fluid-attenuated
      inversion recovery (FLAIR) vascular hyperintensities (FVHs), collateralization on
      dynamic 4D angiograms) and investigate its relation to ischemic lesion size and
      growth. METHODS: In 28 patients with posterior cerebral artery (PCA) and 10
      patients with basilar artery (BA) occlusion, MRI findings were analyzed, with
      emphasis on distal FVH and collateralization on dynamic 4D angiograms. RESULTS:
      In PCA occlusion, distal FVH was observed in 18/29 (62.1%), in BA occlusion, in
      8/10 (80%) cases. Collateralization on dynamic 4D angiograms was graded 1 in 8
      (27.6%) patients, 2 in 1 (3.4%) patient, 3 in 12 (41.4%) patients, and 4 in 8
      (27.6%) patients with PCA occlusion and 0 in 1 (10%) patient, 2 in 3 (30%)
      patients, 3 in 1 (10%) patient, and 4 in 5 (50%) patients with BA occlusion. FVH
      grade showed neither correlation with initial or follow-up diffusion-weighted
      image (DWI) lesion size nor DWI-perfusion-weighted imaging (PWI) mismatch ratio.
      Collateralization on dynamic 4D angiograms correlated inversely with initial DWI
      lesion size and moderately with the DWI-(PWI) mismatch ratio. The combination of
      distal FVH and collateralization grade on dynamic 4D angiograms correlated
      inversely with initial as well as follow-up DWI lesion size and highly with the
      DWI-PWI mismatch ratio. CONCLUSIONS: In posterior circulation occlusion, FVH is a
      frequent finding, but its prognostic value is limited. Dynamic 4D angiograms are
      advantageous to examine and graduate collateral blood flow. The combination of
      both parameters results in an improved characterization of collateral blood flow
      and might have prognostic relevance.

PMID- 24866828
TI  - Isoprenoid phosphonophosphates as glycosyltransferase acceptor substrates.
AB  - Glycosyltransferases that act on polyprenol pyrophosphate substrates are
      challenging to study because their lipid-linked substrates are difficult to
      isolate from natural sources and arduous to synthesize. To facilitate access to
      glycosyl acceptors, we assembled phosphonophosphate analogues and showed these
      are effective substrate surrogates for GlfT1, the essential product of
      mycobacterial gene Rv3782. Under chemically defined conditions, the
      galactofuranosyltransferase GlfT1 catalyzes the formation of a tetrasaccharide
      sequence en route to assembly of the mycobacterial galactan. 

PMID- 24866830
TI  - A near-infrared-emitting fluorescent probe for monitoring mitochondrial pH.
AB  - We demonstrate a new small molecule fluorescent probe, possessing near-infrared
      (NIR) emission and an unusually large Stokes shift. It can be readily taken up by
      live cells and mitochondria, and track subtle pH changes with effectively reduced
      biological background fluorescence and improved measurement accuracy. 

PMID- 24866829
TI  - A firmer understanding of the effect of hypergravity on thyroid tissue:
      cholesterol and thyrotropin receptor.
AB  - Maintaining a good health requires the maintenance of a body homeostasis which
      largely depends on correct functioning of thyroid gland. The cells of the thyroid
      tissue are strongly sensitive to hypogravity, as already proven in mice after
      returning to the earth from long-term space missions. Here we studied whether
      hypergravity may be used to counteract the physiological deconditioning of long
      duration spaceflight. We investigated the influence of hypergravity on key lipids
      and proteins involved in thyroid tissue function. We quantified cholesterol (CHO)
      and different species of sphingomyelin (SM) and ceramide, analysed thyrotropin
      (TSH) related molecules such as thyrotropin-receptor (TSHR), cAMP, Caveolin-1 and
      molecule signalling such as Signal transducer and activator of transcription-3
      (STAT3). The hypergravity treatment resulted in the upregulation of the TSHR and
      Caveolin-1 and downregulation of STAT3 without changes of cAMP. TSHR lost its
      specific localization and spread throughout the cell membrane; TSH treatment
      facilitated the shedding of alpha subunit of TSHR and its releasing into the
      extracellular space. No specific variations were observed for each species of SM
      and ceramide. Importantly, the level of CHO was strongly reduced. In conclusion,
      hypergravity conditions induce change in CHO and TSHR of thyroid gland. The
      possibility that lipid rafts are strongly perturbed by hypergravity-induced CHO
      depletion by influencing TSH-TSHR interaction was discussed. 

PMID- 24866831
TI  - Emergent patterns of population genetic structure for a coral reef community.
AB  - What shapes variation in genetic structure within a community of codistributed
      species is a central but difficult question for the field of population genetics.
      With a focus on the isolated coral reef ecosystem of the Hawaiian Archipelago, we
      assessed how life history traits influence population genetic structure for 35
      reef animals. Despite the archipelago's stepping stone configuration, isolation
      by distance was the least common type of genetic structure, detected in four
      species. Regional structuring (i.e. division of sites into genetically and
      spatially distinct regions) was most common, detected in 20 species and nearly in
      all endemics and habitat specialists. Seven species displayed chaotic (spatially
      unordered) structuring, and all were nonendemic generalist species. Chaotic
      structure also associated with relatively high global FST. Pelagic larval
      duration (PLD) was not a strong predictor of variation in population structure
      (R2=0.22), but accounting for higher FST values of chaotic and invertebrate
      species, compared to regionally structured and fish species, doubled the power of
      PLD to explain variation in global FST (adjusted R2=0.50). Multivariate
      correlation of eight species traits to six genetic traits highlighted dispersal
      ability, taxonomy (i.e. fish vs. invertebrate) and habitat specialization as
      strongest influences on genetics, but otherwise left much variation in genetic
      traits unexplained. Considering that the study design controlled for many
      sampling and geographical factors, the extreme interspecific variation in spatial
      genetic patterns observed for Hawaii marine species may be generated by
      demographic variability due to species-specific abundance and migration patterns
      and/or seascape and historical factors.

PMID- 24866832
TI  - Combined therapy with intravitreal bevacizumab and posterior subtenon
      triamcinolone acetonide injection in diabetic macular oedema.

PMID- 24866834
TI  - Is an endoscopic approach superior to external dacryocystorhinostomy for
      nasolacrimal obstruction?

PMID- 24866833
TI  - Expression of glucagon-like peptide-1 receptor and glucose-dependent
      insulinotropic polypeptide receptor is regulated by the glucose concentration in
      mouse osteoblastic MC3T3-E1 cells.
AB  - Glucose-dependent insulinotropic polypeptide receptor (GIPR) and glucagon-like
      peptide-1 receptor (GLP-1R) are incretin receptors that play important roles in
      regulating insulin secretion from pancreatic beta cells. Incretin receptors are
      also thought to play a potential role in bone metabolism. Osteoblasts in animals
      and humans express GIPR; however, the presence of GLP-1R in these cells has not
      been reported to date. Thus, the aim of this study was to determine whether GLP
      1R and GIPR are expressed in osteoblastic cells, and whether their expression
      levels are regulated by the extracellular glucose concentration. Mouse
      osteoblastic MC3T3-E1 cells were cultured in medium containing normal (5.6 mM) or
      high (10, 20 or 30 mM) glucose concentrations, with or without bone morphogenetic
      protein-2 (BMP-2). RT-PCR, western blot analysis and immunofluorescence were
      carried out to determine GIPR and GLP-1R mRNA and protein expression levels. Cell
      proliferation was also assessed. The GLP-1R and GIPR mRNA expression levels were
      higher in the MC3T3-E1 cells cultured in medium containing high glucose
      concentrations with BMP-2 compared with the cells cultured in medium containing
      normal glucose concentrations with or without BMP-2. GLP-1R protein expression
      increased following culture in high-glucose medium with BMP-2 compared with
      culture under normal glucose conditions. However, the cellular localization of
      GLP-1R was not affected by either glucose or BMP-2. In conclusion, our data
      demonstrate that the expression of GLP-1R and GIPR is regulated by glucose
      concentrations in MC3T3-E1 cells undergoing differentiation induced by BMP-2. Our
      results reveal the potential role of incretins in bone metabolism.

PMID- 24866835
TI  - Newly defined landmarks for a three-dimensionally based cephalometric analysis: a
      retrospective cone-beam computed tomography scan review.
AB  - OBJECTIVES: To identify two novel three-dimensional (3D) cephalometric landmarks
      and create a novel three-dimensionally based anteroposterior skeletal measurement
      that can be compared with traditional two-dimensional (2D) cephalometric
      measurements in patients with Class I and Class II skeletal patterns. MATERIALS
      AND METHODS: Full head cone-beam computed tomography (CBCT) scans of 100 patients
      with all first molars in occlusion were obtained from a private practice.
      InvivoDental 3D (version 5.1.6, Anatomage, San Jose, Calif) was used to analyze
      the CBCT scans in the sagittal and axial planes to create new landmarks and a
      linear 3D analysis (M measurement) based on maxillary and mandibular centroids.
      Independent samples t-test was used to compare the mean M measurement to
      traditional 2D cephalometric measurements, ANB and APDI. Interexaminer and
      intraexaminer reliability were evaluated using 2D and 3D scatterplots. RESULTS:
      The M measurement, ANB, and APDI could statistically differentiate between
      patients with Class I and Class II skeletal patterns (P < .001). The M
      measurement exhibited a correlation coefficient (r) of -0.79 and 0.88 with APDI
      and ANB, respectively. CONCLUSIONS: The overall centroid landmarks and the M
      measurement combine 2D and 3D methods of imaging; the measurement itself can
      distinguish between patients with Class I and Class II skeletal patterns and can
      serve as a potential substitute for ANB and APDI. The new three-dimensionally
      based landmarks and measurements are reliable, and there is great potential for
      future use of 3D analyses for diagnosis and research.

PMID- 24866836
TI  - Effect of different sterilization modes on the surface morphology, ion release,
      and bone reaction of retrieved micro-implants.
AB  - OBJECTIVE: To compare as-received and sterilized micro-implants in order to
      assess the prospects of reusing them. MATERIALS AND METHODS: Forty micro-implants
      from a single manufacturing lot were used in the study. Thirty were retrieved
      from patients after successful service in their mouth and with no signs of
      failure. The retrieved micro-implants were divided into three groups, according
      to method of sterilization: autoclave, gamma radiation, or ultraviolet radiation.
      All groups were subjected to scanning electron microscope analysis for surface
      morphology assessment. The specimens were immersed in a standard simulated body
      fluid solution kept at 37 degrees C in an incubator; the solution was then
      withdrawn at 24 hours and 30 days to evaluate aluminum and vanadium ion release
      by atomic absorption spectrophotometer in parts per billion. The micro-implants
      were then surgically implanted into the tibia of rabbits for a 1-month healing
      period, and the bone-implant blocks were processed for routine histologic
      examination. RESULTS: This study revealed that sterilized micro-implants had
      altered surface topography, different ion release values, and different
      histologic cell reactions than the as-received micro-implants. CONCLUSIONS:
      Within the limitations of this study, it can be concluded that retrieved self
      drilling micro-implants have tip sharpness variations that require correction
      before insertion by bone drilling. The autoclave-sterilized micro-implants showed
      better histologic results than micro-implants sterilized by gamma or ultraviolet
      rays.

PMID- 24866837
TI  - Enzyme-catalyzed synthesis of saccharide acrylate monomers from nonedible
      biomass.
AB  - Various cellulase preparations were found to catalyze the transglycosidation
      between cotton linters and 2-hydroxyethyl acrylate. The conversion and enzyme
      activity were found to be optimal in reaction mixtures that contained 5 vol % of
      the acrylate. The structures of the products were revealed by using TLC and (1) H
      and (13) C NMR spectroscopy. The enzyme-catalyzed reaction resulted in two
      products. The minor product originated from transglycosidation to hemicellulose
      and was found to be 2-(beta-xylosyloxy)-ethyl acrylate. The major product was
      identified as 2-(beta-glucosyloxy)-ethyl acrylate and the yield of the product
      was 5 wt % based on the amount of consumed cellulose. Glycosidation products with
      oligosaccharide moieties could not be detected in the reaction mixture. This
      result can be explained by the hydrolytic activities of the used cellulase
      preparation. Cellulase from Trichoderma reesei was found to possess, in addition
      to endoglucanase activity, cellobiosidase and beta-glucosidase activities. Five
      other cellulase preparations from different origins were tested as well for
      catalysis of oligosaccharide acrylate synthesis. For most cellulase preparations
      the major transglycosidation product appeared to be 2-(beta-glucosyloxy)-ethyl
      acrylate. Nevertheless, the endo-beta-(1,4)-glucanase from Trichoderma
      longibrachiatum was found to catalyze the synthesis of 2-(beta-cellobiosyloxy)
      ethyl acrylate. Unlike the other cellulase preparations, endo-beta-(1,4)
      glucanase from T. longibrachiatum showed no detectable beta-glucosidase activity
      and therefore oligosaccharide acrylate monomers were not further hydrolyzed into
      the monosaccharide acrylate 2-(beta-glucosyloxy)-ethyl acrylate. 

PMID- 24866838
TI  - "It's not that straightforward": when family support is challenging for mothers
      living with mental illness.
AB  - OBJECTIVE: Mental health service providers often have limited or problematic
      understanding of parents' support needs or experiences and family relationships.
      Moreover, the impact of family life and relationships for mothers with mental
      illness, and whether these relationships are experienced as positive or negative,
      have been largely underinvestigated. This article aims to increase understanding
      about the complexity of family relationships and support for mothers. Findings
      may be useful for services when considering family involvement, and for how to
      better meet the needs of mothers with mental illness and support their recovery.
      METHOD: Semistructured interviews were conducted with 8 mothers with mental
      illness and 11 mental health service providers. This article presents a grounded
      theory analysis of the complexity of family relationships and support for mothers
      with mental illness. RESULTS: Family relationships of mothers with mental illness
      can be complex, potentially difficult, and challenging. Problems in relationships
      with partners and families, and experiences of abuse, can have harmful
      consequences on parenting, on mothers' and children's well-being, and on the
      support mothers receive. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: This project
      highlights a need to recognize and work with positive aspects and difficulties in
      family relationships as part of mental health service provision. Policies can be
      reviewed to increase the likelihood that mental health care will combine family
      sensitive practice with practice that acknowledges difficult family relationships
      and experiences of family violence in order to maximize support to mothers with
      mental illness and their children.

PMID- 24866839
TI  - Parenting and psychiatric rehabilitation: can parents with severe mental illness
      benefit from a new approach?
AB  - OBJECTIVE: The aim of this pilot implementation study was to explore the initial
      experiences with and impact of Parenting with Success and Satisfaction (PARSS), a
      psychiatric rehabilitation and recovery-based, guided self-help intervention, for
      parents with severe mental illnesses. METHODS: Changes in the PARSS intervention
      group were compared with changes in a control group in a nonequivalent control
      group design. Outcome measures included: parenting satisfaction reported by
      parents; parenting success reported by mental health practitioners and family
      members; empowerment as reported by parents, practitioners and family members;
      and parents' reported quality of life. Additional process data were obtained on
      relationship with practitioner, quality of contact, satisfaction with the
      intervention and fidelity. RESULTS: Parenting satisfaction increased after 1 year
      for the PARSS group, but not for the control group. Parents' reports of
      empowerment did not change for either group. The scores of parents' empowerment
      reported by practitioners and family members increased in the control group, with
      no such change in the PARSS group. Quality of life improved significantly for the
      intervention group. Process measures showed that, although PARSS was not always
      implemented as intended, both parents and practitioners expressed satisfaction
      with the intervention. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: The first
      experiences with PARSS were mixed. This intervention, implemented by mental
      health practitioners, has the potential to function as a useful tool for
      supporting parents. Attention must be paid to enhancing intervention
      implementation and fidelity.

PMID- 24866841
TI  - Short- and long-term treatment with folic acid suppresses thrombus formation in
      atherogenic mice in vivo.
AB  - In the present study, we examined the effects of short- and long-term treatment
      with folic acid (FA) on thrombus formation in vivo in atherogenic mice to explore
      a novel agent for the prevention of atherothrombotic disease. Apolipoprotein E
      and low-density lipoprotein receptor double deficient (ApoE(-/-)LDLR(-/-)) mice
      were orally administrated a single bolus of FA (20mg/kg) or fed an atherogenic
      diet with or without FA (0.02, 0.5, and 1.5mg/kg) for 12 weeks. Thrombus
      formation and endothelial function were assessed in vivo using the He-Ne laser
      induced carotid artery thrombus formation test and the flow-mediated vasodilation
      method. Platelet reactivity was assessed ex vivo using haemostatometry. Short
      term treatment with FA markedly increased plasma folate levels and significantly
      suppressed laser-induced thrombus formation in apoE(-/-)LDLR(-/-) mice. Short
      term treatment with FA suppressed platelet reactivity in apoE(-/-)LDLR(-/-) mice,
      but FA treatment did not affect endothelial function or plasma homocysteine
      levels. Long-term treatment with FA increased plasma folate levels dose
      dependently. Thrombus formation and endothelial dysfunction were suppressed by
      treatment with 0.5 and 1.5mg/kg of FA, respectively, but not with 0.02mg/kg of
      FA, whereas platelet reactivity was not altered by treatment with any dose of FA.
      Long-term treatment with all doses of FA decreased the plasma homocysteine levels
      in apoE(-/-)LDLR(-/-) mice, although this result was not consistent with its anti
      thrombotic action. In conclusion, our data showed that short- and long-term
      treatment with FA could suppress in vivo thrombus formation in an atherogenic
      setting, independent of its hypohomocysteinemic action. 

PMID- 24866840
TI  - High incidence of HIV-1 infection in a general population of fishing communities
      around Lake Victoria, Uganda.
AB  - BACKGROUND: High HIV-1 incidence rates were reported among persons in fisherfolk
      communities (FFC) in Uganda who were selected for high risk behaviour. We
      assessed the incidence of HIV-1 and associated risk factors in a general
      population FFC to determine population-wide HIV rates. METHODS: A community-based
      cohort study was conducted among a random sample of 2191 participants aged 18-49
      years. At baseline and 12 months post-baseline, data were collected on socio
      demographic characteristics and risky behaviors (including number of partners,
      new partners, condom use, use of alcohol and illicit drug use). Venous blood was
      collected for HIV serological testing. HIV incidence was calculated per 100
      person years at-risk (pyar) and adjusted incidence rate ratios (Adj.IRR) were
      estimated by multivariable Poisson regression. RESULTS: Overall follow up at 12
      months was 76.9% (1685/2191) and was significantly higher among HIV uninfected
      persons and those with at least 1 year duration of stay in community. Overall HIV
      1 incidence was 3.39/100 pyar (95% CI: 2.55-4.49). Among the 25-29 years who
      drank alcohol, HIV incidence was 7.67/100 pyar (95% CI;4.62-12.7) while it was
      5.67/100 pyar (95% CI;3.14-10.2) for 18-24 year olds who drank alcohol. The risk
      of HIV infection was higher among 25-29 years (adj.IRR = 3.36; 95% CI: 1.48-7.65)
      and 18-24 years (adj.IRR = 2.65; 95% CI: 1.05-6.70) relative to 30+ years.
      Compared to non-drinkers, HIV incidence increased by frequency of alcohol
      drinking--occasional drinkers (adj.IRR = 3.18; 95% CI: 1.18-8.57) and regular
      drinkers (adj.IRR = 4.93; 95% CI: 1.91-12.8). CONCLUSION: HIV-1 incidence in
      general fisherfolk population along L. Victoria, Uganda, is high and is mainly
      associated with young age and alcohol drinking. HIV prevention and control
      strategies are urgently needed in this population.

PMID- 24866846
TI  - Early life effects across the life course: the impact of individually defined
      exogenous measures of disease exposure on mortality by sex in 19th- and 20th
      century Southern Sweden.
AB  - Using micro-level longitudinal data from Southern Sweden for 1813 to 1968, this
      work evaluates the effect of exposure to disease in early life on mortality over
      the entire life course and separately by sex. The local rates of post-early
      neonatal mortality are considered indicators of early life disease exposure, and
      these rates are calculated specifically for each person based on birth date. The
      loss in median remaining life among exposed individuals who survived to age 1 is
      1.1 years for females and 2.1 years for males. Exposed individuals show a cross
      over from lower to higher relative mortality as they age. This change occurs in
      adulthood for males and in old age for females. During adulthood, exposed males
      present higher rates of death than exposed females. These results are new to the
      literature and shed light on the importance of adopting a full life course
      approach and capturing sex differences when evaluating the long-term impacts of
      early life exposures. 

PMID- 24866847
TI  - Determinants of time to surgery for patients with hip fracture.
AB  - BACKGROUND: Guidelines for hip fracture care suggest that patients with hip
      fracture should undergo surgery on the day of or day after admission to hospital.
      This study examined factors affecting time to surgery for hip fracture extracted
      from existing administrative datasets in New South Wales (NSW), Australia.
      METHOD: A retrospective analysis of patients with hip fracture aged 65 years and
      over undergoing surgical intervention in NSW public hospitals between 1 July 2000
      and 30 June 2011. A multinomial logistic model was used to identify factors
      impacting on time to surgery from 1 July 2006 to 30 June 2011. RESULTS: A total
      of 49,317 hip fracture procedures were recorded during 2000-2001 to 2010-2011.
      Sixty-four per cent of patients received operative treatment on the day of or day
      after admission. Co-morbidity, type of surgical procedure and day of presentation
      all impacted significantly on time to surgery. Fourteen per cent required an
      inter-hospital transfer prior to receiving operative intervention. Transferred
      patients were 2.6 (95% confidence interval (CI): 2.31-2.85) times more likely to
      wait 2-4 days and 3.2 times more likely to wait 5 or more days (95% CI: 2.77
      3.76) for surgery compared with patients presenting to an operating hospital.
      CONCLUSION: Significant variation exists between hospitals in the time to surgery
      that is not solely explained by measures of case mix or geography. Opportunities
      exist to consider other factors contributing to this variation and to ensure
      timely access to surgical intervention in the future.

PMID- 24866849
TI  - The novel capripoxvirus vector lumpy skin disease virus efficiently boosts
      modified vaccinia Ankara human immunodeficiency virus responses in rhesus
      macaques.
AB  - Poxvirus vectors represent promising human immunodeficiency virus (HIV) vaccine
      candidates and were a component of the only successful HIV vaccine efficacy trial
      to date. We tested the immunogenicity of a novel recombinant capripoxvirus
      vector, lumpy skin disease virus (LSDV), in combination with modified vaccinia
      Ankara (MVA), both expressing genes from HIV-1. Here, we demonstrated that the
      combination regimen was immunogenic in rhesus macaques, inducing high-magnitude,
      broad and balanced CD4(+) and CD8(+) T-cell responses, and transient activation
      of the immune response. These studies support further development of LSDV as a
      vaccine vector. 

PMID- 24866850
TI  - Baculovirus induces host cell aggregation via a Rho/Rok-dependent mechanism.
AB  - Several baculoviruses can induce host cell aggregation during infection; however,
      the molecular basis remains unknown. The Rho family of small GTPases, including
      Rho1, Racs and Cdc42, plays important roles in cell migration and cell-cell
      contact. Activated GTPases target actin polymerization to discrete sites on the
      plasma membrane, thereby inducing membrane protrusions. In this study, we
      demonstrated that Spodoptera litura nucleopolyhedrovirus (SpltNPV) infection
      induced the amoeboid movement and aggregation of SpLi-221 cells in vitro. The
      amount of Rho1-GTP increased in the infected cells, which suggested that Rho1 was
      activated upon infection. RNA interference and superinfection of dominant
      negative recombinants revealed that the SpltNPV-induced SpLi-221 cell aggregation
      was dependent on the Rho1, but not Racs or Cdc42, signalling pathway. Inhibition
      of Rho-associated protein kinase (Rok) activity by the inhibitor Y-27632
      significantly reduced SpLi-221 cell aggregation. Silencing Rho1 expression with
      RNA interference decreased SpltNPV propagation by approximately 40 % in vitro,
      when SpLi-221 cells were infected at a low, but not high, m.o.i., suggesting that
      the SpltNPV-induced cell aggregation may benefit SpltNPV spread. 

PMID- 24866848
TI  - Concentration-dependent effects of WNTLESS on WNT1/3A signaling.
AB  - BACKGROUND: WNTLESS (WLS) is a multi-transmembrane protein that transports Wnt
      ligands from the Golgi to the cell surface. Although WLS loss-of-function
      experiments in the developing central nervous system reveal phenotypes consistent
      with defects in WNT1 and WNT3A signaling, data from complementary gain-of
      function experiments have not yet been reported. Here, we report the phenotypic
      consequences of WLS overexpression in cultured cells and in the developing chick
      spinal cord. RESULTS: Overexpression of small amounts of WLS along with either
      WNT1 or WNT3A promotes the Wnt/beta-catenin pathway in HEK293T cells, while
      overexpression of higher levels of WLS inhibits the Wnt/beta-catenin pathway in
      these cells. Similarly, overexpressed WLS inhibits the Wnt/beta-catenin pathway
      in the developing spinal cord, as assessed by cell proliferation and
      specification. These effects appear to be Wnt-specific as overexpression of WLS
      inhibits the expression of FZD10, a target of beta-catenin-dependent
      transcription. CONCLUSIONS: Our results show that overexpression of WLS inhibits
      Wnt/beta-catenin signaling in the spinal cord. As the activation of the Wnt/beta
      catenin pathway in the spinal cord requires WNT1 or WNT3A, our results are
      consistent with a model in which the relative concentration of WLS to Wnt
      regulates WNT1/3A signaling in the developing spinal cord.

PMID- 24866851
TI  - Identification of an RNA silencing suppressor encoded by a mastrevirus.
AB  - Wheat dwarf virus (WDV) is a DNA virus belonging to the genus Mastrevirus of the
      family Geminiviridae. In this study, we report that the Rep protein encoded by
      WDV is a RNA silencing supressor as determined by co-infiltration assays using
      transgenic Nicotiana benthamiana line 16c carrying the GFP reporter gene. The Rep
      protein was shown to inhibit both local and systemic RNA silencing of the GFP
      gene as well as the spread of systemic GFP RNA silencing signals. Gel mobility
      shift assays showed that the Rep protein binds 21 nt and 24 nt small interfering
      RNA (siRNA) duplexes and single-stranded (ss)-siRNA. To our knowledge, this is
      the first identification of an RNA silencing suppressor encoded by mastreviruses.
      Furthermore, deletion mutagenesis indicates that both the N- and C-terminal
      regions of the Rep protein are not critical for silencing suppression and self
      interaction, but the N terminus of Rep is necessary for its pathogenicity. 

PMID- 24866853
TI  - Neonatal pain and developmental outcomes in children born preterm: a systematic
      review.
AB  - BACKGROUND: Neonates cared for in neonatal intensive care units are exposed to
      many painful and stressful procedures that, cumulatively, could impact later
      neurodevelopmental outcomes. However, a systematic analysis of these effects is
      yet to be reported. OBJECTIVES: The aim of this research was to review empirical
      studies examining the association between early neonatal pain experiences of
      preterm infants and the subsequent developmental outcomes of these children
      across different ages. METHODS: The literature search was performed using the
      PubMed, PsycINFO, Lilacs, and SciELO databases and included the following key
      words: "pain," "preterm," and "development." In addition, a complementary search
      was performed in online journals that published pain and developmental studies to
      ensure all of the target studies had been found. The data were extracted
      according to predefined inclusion and exclusion criteria. RESULTS: Thirteen
      studies were analyzed. In infants born extremely preterm (gestational age <=29
      wk) greater numbers of painful procedures were associated with delayed postnatal
      growth, with poor early neurodevelopment, high cortical activation, and with
      altered brain development. In toddlers born very preterm (gestational age <=32
      wk) biobehavioral pain reactivity-recovery scores were associated with negative
      affectivity temperament. Furthermore, greater numbers of neonatal painful
      experiences were associated with a poor quality of cognitive and motor
      development at 1 year of age and changes in cortical rhythmicity and cortical
      thickness in children at 7 years of age. CONCLUSIONS: For infants born preterm,
      neonatal pain-related stress was associated with alterations in both early and in
      later developmental outcomes. Few longitudinal studies examined the impact of
      neonatal pain in the long-term development of children born preterm.

PMID- 24866854
TI  - Impact of an Acceptance Facilitating Intervention on Patients' Acceptance of
      Internet-based Pain Interventions: A Randomized Controlled Trial.
AB  - OBJECTIVE: Results from clinical trials indicate that Internet-based
      psychological pain interventions are effective in treating chronic pain. However,
      little is known about patients' acceptance of these programs and how to
      positively influence patients' intention to engage in them. Therefore, the
      present study aimed (1) to assess patients' acceptance of Internet-based
      interventions, and (2) to examine whether patients' acceptance can be increased
      by an acceptance facilitating intervention. METHODS: A total of 104 patients with
      chronic pain from 2 pain units were randomly allocated to an intervention group
      (IG) and a no-intervention control group (CG). The IG was shown a short
      informational video about Internet-based psychological pain interventions before
      receiving a questionnaire on patients' acceptance of Internet-based psychological
      pain interventions and predictors of acceptance (performance expectancy, effort
      expectancy, social influence, facilitating conditions, Internet usage, and
      Internet anxiety). The CG filled out the questionnaire immediately. Patients'
      acceptance was measured with a 4-item scale (sum score ranging from 4 to 20).
      RESULTS: Baseline acceptance of Internet-based interventions was reported as low
      (sum-score:4-9) by 53.8%, moderate (10 to 15) by 42.3%, and high (16 to 20) by
      3.9% of the patients with chronic pain in the CG. The IG showed a significantly
      higher acceptance (M = 12.17, SD = 4.22) than the CG (M = 8.94, SD = 3.71) with a
      standardized mean difference of d = 0.81 (95% CI, 0.41, 1.21). All predictor
      variables were significantly improved in the IG compared with the CG, except for
      Internet usage. CONCLUSIONS: Patients with chronic pain display a relatively low
      acceptance of Internet-based psychological pain interventions, which can be
      substantially increased by a short informational video.

PMID- 24866855
TI  - Pain catastrophizing differs between and within West Haven-Yale Multidimensonal
      Pain Inventory (MPI) pain adjustment classifications: theoretical and clinical
      implications from preliminary data.
AB  - OBJECTIVES: Pain catastrophizing is associated with multiple pain outcomes, and
      is differentially associated with the adaptive coping (AC), dysfunctional (DYS),
      and interpersonally distressed (ID) coping classifications of the West Haven-Yale
      Multidimensional Pain Inventory (MPI). We examined how catastrophizing, and the
      underlying components of magnification, rumination, and helplessness, may relate
      to MPI classifications and differentially relate to pain outcomes across
      classification groups to inform clinical treatment planning. MATERIALS AND
      METHODS: Sixty-nine adults (70% women) diagnosed with musculoskeletal pain were
      recruited from 2 pain clinics and completed self-report measures of pain
      severity, the MPI, Pain Catastrophizing Scale, and the Mood and Anxiety Symptom
      Questionnaire. RESULTS: Patients in the DYS and ID groups reported the greatest
      levels of rumination, helplessness, and overall catastrophizing, as well as the
      greatest depression, anxiety, and pain interference compared with the AC group.
      Catastrophizing related to average pain only in the DYS group (P<0.05), however,
      catastrophizing was associated with depression, anxiety, and interference
      (Ps<0.05) among those in the AC group, with a similar pattern observed among the
      ID group. DISCUSSION: Our findings suggest a continued need for targeting
      catastrophizing and negative affect among pain patients. However, our data
      suggest that even among relatively well-adjusted patients, there may be clinical
      utility in assessing catastrophic thinking given the associations of it with pain
      related outcomes. The present findings additionally support the value of
      enlisting multiple theoretical perspectives such as the stress appraisal and
      attentional models in future research and clinical applications.

PMID- 24866856
TI  - Mechanical hyperalgesia and reduced quality of life occur in people with mild
      knee osteoarthritis pain.
AB  - OBJECTIVES: This study determined whether individuals with mild knee pain due to
      osteoarthritis (OA) experience hyperalgesia and central sensitivity by comparing
      them with age-matched and sex-matched control participants and determined whether
      these levels are associated with pain intensity. This study also determined
      whether these individuals experience significantly poorer quality of life than
      age-matched and sex-matched controls and whether pain and function predict
      quality of life. METHODS: Quantitative sensory tests (QSTs), including punctate
      pain intensity (PPI), pressure pain threshold (PPT), and heat pain threshold,
      tolerance, and temporal summation, were measured in 75 individuals with mild knee
      OA pain and 25 age-matched and sex-matched controls. Pain intensity, walking
      function, and quality of life were also assessed. RESULTS: Significant
      differences were found for PPI at all sites, for PPT at the affected knee, and
      for quality of life. QST measures significantly correlated with pain intensity.
      Pain, but not function, predicted quality of life. DISCUSSION: Individuals with
      mild knee pain due to OA experience mechanical (but not thermal) hyperalgesia
      that relates to pain intensity. They have a reduced quality of life that is
      predicted by pain intensity. More aggressive pain management for mild knee OA
      pain is indicated to improve the quality of life for individuals who are not yet
      candidates for joint replacement.

PMID- 24866857
TI  - Quantifying risk of kidney donation: the truth is not out there (yet).
AB  - This editorial offers a counterpoint to the findings of increased mortality in
      living kidney donors in a study by Mjoen et al that has been widely discussed in
      the transplant community.

PMID- 24866858
TI  - A bond-order theory on the phonon scattering by vacancies in two-dimensional
      materials.
AB  - We theoretically investigate the phonon scattering by vacancies, including the
      impacts of missing mass and linkages (tau(V)(-1)) and the variation of the force
      constant of bonds associated with vacancies (tau(A)(-1)) by the bond-order-length
      strength correlation mechanism. We find that in bulk crystals, the phonon
      scattering rate due to change of force constant tau(A)(-1) is about three orders
      of magnitude lower than that due to missing mass and linkages tau(V)(-1). In
      contrast to the negligible tau(A)(-1) in bulk materials, tau(A)(-1) in two
      dimensional materials can be 3-10 folds larger than tau(V)(-1). Incorporating
      this phonon scattering mechanism to the Boltzmann transport equation derives that
      the thermal conductivity of vacancy defective graphene is severely reduced even
      for very low vacancy density. High-frequency phonon contribution to thermal
      conductivity reduces substantially. Our findings are helpful not only to
      understand the severe suppression of thermal conductivity by vacancies, but also
      to manipulate thermal conductivity in two-dimensional materials by phononic
      engineering.

PMID- 24866859
TI  - Agenesis of the corpus callosum: a clinical approach to diagnosis.
AB  - This review article aims to guide the clinician in establishing a diagnosis in
      patients with agenesis of the corpus callosum (ACC), presenting antenatally or
      postnatally. ACC may be isolated, or occur in association with other
      neuroanatomical lesions and/or congenital anomalies, and has many different
      genetic causes. Neuropsychological outcome varies considerably from normal to
      profound intellectual disability depending on the etiology. Approximately 25% of
      individuals with antenatally diagnosed apparently isolated ACC have intellectual
      disability. Subtle neurological, social, and learning deficits may still occur in
      those with normal intelligence and longitudinal neurocognitive follow-up is
      recommended for all children with ACC. The finding of ACC should prompt detailed
      clinical assessment in order to determine and manage the underlying condition. It
      is recognized that genetic factors contribute to ACC in the vast majority of
      cases. Less commonly ACC can result from antenatal infections, vascular or toxic
      insults, and it is increasingly recognized that ACC, particularly isolated ACC,
      may be due to an interaction of a number of "modifier" genetic and environmental
      factors. There are a large number of genetic conditions in which ACC may be a
      feature. We suggest a diagnostic algorithm to help guide the clinician towards
      diagnosis, to provide outcome advice and to aid in genetic counseling.

PMID- 24866852
TI  - Pharmacological manipulations in animal models of anorexia and binge eating in
      relation to humans.
AB  - Eating disorders, such as anorexia nervosa (AN), bulimia nervosa (BN) and binge
      eating disorders (BED), are described as abnormal eating habits that usually
      involve insufficient or excessive food intake. Animal models have been developed
      that provide insight into certain aspects of eating disorders. Several drugs have
      been found efficacious in these animal models and some of them have eventually
      proven useful in the treatment of eating disorders. This review will cover the
      role of monoaminergic neurotransmitters in eating disorders and their
      pharmacological manipulations in animal models and humans. Dopamine, 5-HT
      (serotonin) and noradrenaline in hypothalamic and striatal regions regulate food
      intake by affecting hunger and satiety and by affecting rewarding and
      motivational aspects of feeding. Reduced neurotransmission by dopamine, 5-HT and
      noradrenaline and compensatory changes, at least in dopamine D2 and 5-HT(2C/2A)
      receptors, have been related to the pathophysiology of AN in humans and animal
      models. Also, in disorders and animal models of BN and BED, monoaminergic
      neurotransmission is down-regulated but receptor level changes are different from
      those seen in AN. A hypofunctional dopamine system or overactive alpha2
      adrenoceptors may contribute to an attenuated response to (palatable) food and
      result in hedonic binge eating. Evidence for the efficacy of monoaminergic
      treatments for AN is limited, while more support exists for the treatment of BN
      or BED with monoaminergic drugs.

PMID- 24866861
TI  - Protein secondary structure classification revisited: processing DSSP information
      with PSSC.
AB  - A first step toward three-dimensional protein structure description is the
      characterization of secondary structure. The most widely used program for
      secondary structure assignment remains DSSP, introduced in 1983, with currently
      more than 400 citations per year. DSSP output is in a one-letter representation,
      where much of the information on DSSP's internal description is lost. Recently it
      became evident that DSSP overlooks most pi-helical structures, which are more
      prevalent and important than anticipated before. We introduce an alternative
      concept, representing the internal structure characterization of DSSP as an eight
      character string that is human-interpretable and easy to parse by software. We
      demonstrate how our protein secondary structure characterization (PSSC) code
      allows for inspection of complicated structural features. It recognizes ten times
      more pi-helical residues than does the standard DSSP. The plausibility of
      introduced changes in interpreting DSSP information is demonstrated by better
      clustering of secondary structures in (phi, psi) dihedral angle space. With a
      sliding sequence window (SSW), helical assignments with PSSC remain invariant
      compared with an assignment based on the complete structure. In contrast,
      assignment with DSSP can be changed by residues in the neighborhood that are in
      fact not interacting with the residue under consideration. We demonstrate how one
      can easily define new secondary structure classification schemes with PSSC and
      perform the classifications. Our approach works without changing the DSSP source
      code and allows for more detailed protein characterization. 

PMID- 24866863
TI  - Comparison of a closed system to a standard open technique for preparing tissue
      engineered vascular grafts.
AB  - We developed a prototype for a closed apparatus for assembling tissue-engineered
      vascular grafts (TEVGs) with the goal of creating a simple operator-independent
      method for making TEVGs to optimize safety and enable widespread application of
      this technology. The TEVG is made by seeding autologous bone marrow-derived
      mononuclear cells onto a biodegradable tubular scaffold and is the first man-made
      vascular graft to be successfully used in humans. A critical barrier, which has
      prevented the widespread clinical adoption of the TEVG, is that cell isolation,
      scaffold seeding, and incubation are performed using an open method. To reduce
      the risk of contamination, the TEVG is assembled in a clean room. Clean rooms are
      expensive to build, complex to operate, and are not available in most hospitals.
      In this investigation, we used an ovine model to compare the safety and efficacy
      of TEVGs created using either a standard density centrifugation-based open method
      or the new filter-based closed system. We demonstrated no graft-related
      complications and maintenance of growth capacity in TEVGs created using the
      closed apparatus. In addition, the use of the closed system reduced the amount of
      time needed to assemble the TEVG by ~ 50%. Adaptation of similar methodologies
      may facilitate the safe translation and the widespread use of other tissue
      engineering technologies.

PMID- 24866865
TI  - Terrestrial laser scanning and a degenerated cylinder model to determine gross
      morphological change of cadavers under conditions of natural decomposition.
AB  - Decomposition can be a highly variable process with stages that are difficult to
      quantify. Using high accuracy terrestrial laser scanning a repeated three
      dimensional (3D) documentation of volumetric changes of a human body during early
      decomposition is recorded. To determine temporal volumetric variations as well as
      3D distribution of the changed locations in the body over time, this paper
      introduces the use of multiple degenerated cylinder models to provide a
      reasonable approximation of body parts against which 3D change can be measured
      and visualized. An iterative closest point algorithm is used for 3D registration,
      and a method for determining volumetric change is presented. Comparison of the
      laser scanning estimates of volumetric change shows good agreement with repeated
      in-situ measurements of abdomen and limb circumference that were taken diurnally.
      The 3D visualizations of volumetric changes demonstrate that bloat is a process
      with a beginning, middle, and end rather than a state of presence or absence.
      Additionally, the 3D visualizations show conclusively that cadaver bloat is not
      isolated to the abdominal cavity, but also occurs in the limbs. Detailed
      quantification of the bloat stage of decay has the potential to alter how the
      beginning and end of bloat are determined by researchers and can provide further
      insight into the effects of the ecosystem on decomposition. 

PMID- 24866864
TI  - Intimate partner sexual and physical violence among women in Togo, West Africa:
      prevalence, associated factors, and the specific role of HIV infection.
AB  - BACKGROUND: A substantial proportion of newly diagnosed HIV infections in sub
      Saharan Africa occur within serodiscordant cohabiting heterosexual couples.
      Intimate partner violence is a major concern for couple-oriented HIV preventive
      approaches. This study aimed at estimating the prevalence and associated factors
      of intimate partner physical and sexual violence among HIV-infected and 
      uninfected women in Togo. We also described the severity and consequences of this
      violence as well as care-seeking behaviors of women exposed to intimate partner
      violence. METHODS: A cross-sectional survey was conducted between May and July
      2011 within Sylvanus Olympio University Hospital in Lome. HIV-infected women
      attending HIV care and uninfected women attending postnatal care and/or children
      immunization visits were interviewed. Intimate partner physical and sexual
      violence and controlling behaviors were assessed using an adapted version of the
      WHO Multi-country study on Women's Health and Life Events questionnaire. RESULTS:
      Overall, 150 HIV-uninfected and 304 HIV-infected women accepted to be
      interviewed. The prevalence rates of lifetime physical and sexual violence among
      HIV-infected women were significantly higher than among uninfected women (63.1
      vs. 39.3%, p<0.01 and 69.7 vs. 35.3%, p<0.01, respectively). Forty-two percent of
      the women reported having ever had physical injuries as a consequence of intimate
      partner violence. Among injured women, only one-third had ever disclosed real
      causes of injuries to medical staff and none of them had been referred to local
      organizations to receive appropriate psychological support. Regardless of HIV
      status and after adjustment on potential confounders, the risk of intimate
      partner physical and sexual violence was strongly and significantly associated
      with male partner multi-partnership and early start of sexual life. Among
      uninfected women, physical violence was significantly associated with gender
      submissive attitudes. DISCUSSION AND CONCLUSIONS: The prevalence rates of both
      lifetime physical and sexual violence were very high among HIV-uninfected women
      and even higher among HIV-infected women recruited in health facilities in this
      West African country. Screening for intimate partner violence should be
      systematic in health-care settings, and specifically within HIV care services. At
      a time of increased investments in couple-oriented HIV prevention interventions,
      further longitudinal research to better understanding of HIV-serodiscordant
      couple dynamics in terms of intimate partner violence is needed.

PMID- 24866866
TI  - Assessment and forensic application of laser-induced breakdown spectroscopy
      (LIBS) for the discrimination of Australian window glass.
AB  - A commercially available laser-induced breakdown spectroscopy (LIBS) instrument
      was evaluated for the determination of elemental composition of twenty Australian
      window glass samples, consisting of 14 laminated samples and 6 non-laminated
      samples (or not otherwise specified) collected from broken windows at crime
      scenes. In this study, the LIBS figures of merit were assessed in terms of
      accuracy, limits of detection and precision using three standard reference
      materials (NIST 610, 612, and 1831). The discrimination potential of LIBS was
      compared to that obtained using laser ablation inductively coupled plasma mass
      spectrometry (LA-ICP-MS), X-ray microfluorescence spectroscopy (MUXRF) and
      scanning electron microscopy energy dispersive X-ray spectrometry (SEM-EDX) for
      the analysis of architectural window glass samples collected from crime scenes in
      the Canberra region, Australia. Pairwise comparisons were performed using a three
      sigma rule, two-way ANOVA and Tukey's HSD test at 95% confidence limit in order
      to investigate the discrimination power for window glass analysis. The results
      show that the elemental analysis of glass by LIBS provides a discrimination power
      greater than 97% (>98% when combined with refractive index data), which was
      comparable to the discrimination powers obtained by LA-ICP-MS and MUXRF. These
      results indicate that LIBS is a feasible alternative to the more expensive LA-ICP
      MS and MUXRF options for the routine forensic analysis of window glass samples. 

PMID- 24866869
TI  - Electron transfers in a TiO2-containing MOR zeolite: synthesis of the
      nanoassemblies and application using a probe chromophore molecule.
AB  - New assemblies constituted by a microporous matrix of mordenite (MOR) zeolite on
      which TiO2 nanoclusters are deposited were synthesized using ionic oxalate
      complexes and TiCl3 titanium precursors. The samples were used to investigate the
      transfer of electrons produced by spontaneous or photo-induced ionization of a
      guest molecule (t-stilbene, t-St) occluded in the porous volume towards the
      conduction band of a conductive material placed nearby, in the pores or at least
      close to their entrance. The reaction mechanisms were compared in these Ti-rich
      solids and in a Ti-free mordenite sample. The characterization by XRD, N2
      physisorption, TEM, XPS and DRIFT spectroscopy of the supramolecular TiO2/MOR
      systems before t-St adsorption showed the preservation of the crystalline
      structure after Ti addition and thermal activation treatments. They also revealed
      that titanium is mainly located at the external surface of the zeolite grains, in
      the form of highly dispersed and/or aggregated anatase. After incorporation of
      the guest molecule in the new assemblies, diffuse reflectance UV-visible and EPR
      spectroscopies indicate that the electron transfer processes are similar with and
      without TiO2 but strongly stabilized t-St(+) radicals are detected in the TiO2
      MOR samples whereas such species were never detected earlier in TiO2-free
      mordenite using these techniques. The stabilization process is found to be more
      efficient in the sample prepared with TiCl3 as the precursor than with titanium
      oxalates. It is proposed that the proximity of TiO2 with the formed t-St(+)
      radicals provokes the stabilization of the radical through capture of the ejected
      electron by the semi-conductor and that confinement effects can also play a role.

PMID- 24866867
TI  - Markers of left ventricular decompensation in aortic stenosis.
AB  - Calcified aortic stenosis is a condition that affects the valve and the
      myocardium. As the valve narrows, left ventricular hypertrophy occurs initially
      as an adaptive mechanism to maintain cardiac output. Ultimately, the ventricle
      decompensates and patients transition towards heart failure and adverse events.
      Current guidelines recommend aortic valve replacement in patients with severe
      aortic stenosis and evidence of decompensation based on either symptoms or an
      impaired ejection fraction <50%. However, symptoms can be subjective and
      correlate only modestly with the severity of aortic stenosis whilst impaired
      ejection fraction is an advanced manifestation and often irreversible. In this
      review, the authors will discuss the pathophysiology of left ventricular
      hypertrophy and the transition to heart failure. Subsequently, the authors will
      examine novel biomarkers that may better identify the transition from hypertrophy
      to heart failure and therefore guide the optimal timing for aortic valve
      replacement. 

PMID- 24866862
TI  - Effect of structured physical activity on prevention of major mobility disability
      in older adults: the LIFE study randomized clinical trial.
AB  - IMPORTANCE: In older adults reduced mobility is common and is an independent risk
      factor for morbidity, hospitalization, disability, and mortality. Limited
      evidence suggests that physical activity may help prevent mobility disability;
      however, there are no definitive clinical trials examining whether physical
      activity prevents or delays mobility disability. OBJECTIVE: To test the
      hypothesis that a long-term structured physical activity program is more
      effective than a health education program (also referred to as a successful aging
      program) in reducing the risk of major mobility disability. DESIGN, SETTING, AND
      PARTICIPANTS: The Lifestyle Interventions and Independence for Elders (LIFE)
      study was a multicenter, randomized trial that enrolled participants between
      February 2010 and December 2011, who participated for an average of 2.6 years.
      Follow-up ended in December 2013. Outcome assessors were blinded to the
      intervention assignment. Participants were recruited from urban, suburban, and
      rural communities at 8 centers throughout the United States. We randomized a
      volunteer sample of 1635 sedentary men and women aged 70 to 89 years who had
      physical limitations, defined as a score on the Short Physical Performance
      Battery of 9 or below, but were able to walk 400 m. INTERVENTIONS: Participants
      were randomized to a structured, moderate-intensity physical activity program (n
      = 818) conducted in a center (twice/wk) and at home (3-4 times/wk) that included
      aerobic, resistance, and flexibility training activities or to a health education
      program (n = 817) consisting of workshops on topics relevant to older adults and
      upper extremity stretching exercises. MAIN OUTCOMES AND MEASURES: The primary
      outcome was major mobility disability objectively defined by loss of ability to
      walk 400 m. RESULTS: Incident major mobility disability occurred in 30.1% (246
      participants) of the physical activity group and 35.5% (290 participants) of the
      health education group (hazard ratio [HR], 0.82 [95% CI, 0.69-0.98], P =
      .03).Persistent mobility disability was experienced by 120 participants (14.7%)
      in the physical activity group and 162 participants (19.8%) in the health
      education group (HR, 0.72 [95% CI, 0.57-0.91]; P = .006). Serious adverse events
      were reported by 404 participants (49.4%) in the physical activity group and 373
      participants (45.7%) in the health education group (risk ratio, 1.08 [95% CI,
      0.98-1.20]). CONCLUSIONS AND RELEVANCE: A structured, moderate-intensity physical
      activity program compared with a health education program reduced major mobility
      disability over 2.6 years among older adults at risk for disability. These
      findings suggest mobility benefit from such a program in vulnerable older adults.
      TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01072500.

PMID- 24866870
TI  - Effects of doxazosin as the third agent on morning hypertension and position
      related blood pressure changes in diabetic patients with chronic kidney disease.
AB  - We conducted a prospective study to assess the effects of doxazosin, as the third
      agent, on morning and position-related blood pressure (BP) in 77 diabetic
      patients with chronic kidney disease, who were allocated randomly to doxazosin
      and diuretics groups. Doxazosin decreased morning BP but diuretics could not
      decrease pre-awakening diastolic BP. Only doxazosin improved sympathovagal
      balance. Doxazosin and diuretics decreased standing and sitting BP but only
      doxazosin improved sympathovagal balance regardless of body positions. Doxazosin
      did not decrease absolute BP changes shortly after standing. In diabetic
      patients, doxazosin decreased morning BP through improving sympathovagal balance
      without causing significant orthostatic hypotension (ClinicalTrials.gov number,
      NCT00295555).

PMID- 24866875
TI  - Headache: Medication overuse headache--seeking a management consensus.

PMID- 24866880
TI  - Multiple sclerosis: Pegylated IFN-beta1a could lessen patients' injection burden.

PMID- 24866874
TI  - The clinical approach to autonomic failure in neurological disorders.
AB  - Central or peripheral neurological disorders can manifest with autonomic failure
      or autonomic hyperactivity, which may affect the sympathetic, parasympathetic
      and/or enteric nervous systems. Disorders causing autonomic failure can be
      classified according to the presence or absence of associated neurological
      manifestations, such as peripheral neuropathy or parkinsonism, and their temporal
      profile (acute or subacute, chronic progressive, static, or episodic). A
      systematic approach allows focused evaluation to detect treatable, potentially
      disabling or life-threatening conditions. Subacute isolated autonomic failure
      affecting sympathetic, parasympathetic and enteric nervous system function, in
      various combinations, occurs in autoimmune autonomic ganglionopathy, which might
      be the first manifestation of an underlying neoplasm. Autonomic failure can be an
      important feature of several types of peripheral neuropathy, including
      sensorimotor peripheral neuropathies, sensory ganglionopathy, and distal painful
      peripheral neuropathies. Progressive autonomic failure occurs in
      neurodegenerative synucleinopathies such as multiple system atrophy and Lewy body
      disorders. Autonomic failure may also occur in hereditary leukoencephalopathies
      or prion disorders. This Review outlines the clinical approach to patients with
      generalized autonomic failure, focusing predominantly on classification and
      diagnosis, but also touching briefly on treatment and management. 

PMID- 24866883
TI  - Activities of everyday life with high spinal loads.
AB  - Activities with high spinal loads should be avoided by patients with back
      problems. Awareness about these activities and knowledge of the associated loads
      are important for the proper design and pre-clinical testing of spinal implants.
      The loads on an instrumented vertebral body replacement have been telemetrically
      measured for approximately 1000 combinations of activities and parameters in 5
      patients over a period up to 65 months postoperatively. A database containing,
      among others, extreme values for load components in more than 13,500 datasets was
      searched for 10 activities that cause the highest resultant force, bending
      moment, torsional moment, or shear force in an anatomical direction. The
      following activities caused high resultant forces: lifting a weight from the
      ground, forward elevation of straight arms with a weight in hands, moving a
      weight laterally in front of the body with hanging arms, changing the body
      position, staircase walking, tying shoes, and upper body flexion. All activities
      have in common that the center of mass of the upper body was moved anteriorly.
      Forces up to 1650 N were measured for these activities of daily life. However,
      there was a large intra- and inter-individual variation in the implant loads for
      the various activities depending on how exercises were performed. Measured shear
      forces were usually higher in the posterior direction than in the anterior
      direction. Activities with high resultant forces usually caused high values of
      other load components. 

PMID- 24866884
TI  - Citreitalea marina gen. nov., sp. nov., a novel member of the family
      Flavobacteriaceae isolated from a marine red alga and emended description of the
      genus Gangjinia.
AB  - A Gram-negative, strictly aerobic, pale-yellow pigmented, rod-shaped bacterium
      designated A4O-5(T) was isolated from a red coloured marine alga (Chondrus
      ocellatus Holmes). Phylogenetic analyses based on the 16S rRNA gene sequence
      indicated that the new strain was affiliated with the family Flavobacteriaceae
      and shared approximately 90 % sequence similarity with Leptobacterium flavescens
      YM3-0301(T) and Gangjinia marincola GJ16(T). The strain could be differentiated
      phenotypically from the related members of the family Flavobacteriaceae. The
      major fatty acids of strain A4O-5(T) were identified as iso-C15:0, iso-C17:0 3-OH
      and summed feature 3 (C16:1 omega7c and/or C16:1 omega6c). A complex polar lipid
      profile was present consisting of phosphatidylethanolamine, an unidentified
      phospholipid, three unidentified amino lipids and an unidentified lipid. The DNA
      G+C content of the strain was determined to be 41.9 mol% and the major
      respiratory quinone was identified as menaquinone 6 (MK-6). From the distinct
      phylogenetic position and combination of genotypic and phenotypic
      characteristics, the strain is considered to represent a novel genus in the
      family Flavobacteriaceae, for which the name Citreitalea marina gen. nov., sp.
      nov. is proposed. The type strain of C. marina is A4O-5(T) (=KCTC 32483(T)=NBRC
      109918(T)). 

PMID- 24866886
TI  - Conformational preference of potassium salts of N-acylhydrazinecarbodithioates
      with antifungal activity. Combined experimental and theoretical approach.
AB  - In vitro antifungal potency of a set of potassium N-acylhydrazinecarbodithioates
      was tested. Some of the studied salts displayed significant antifungal activity
      against Candida spp. at non-toxic concentration indicating a high selectivity of
      their anticandidal activity. In further study, on the example of conformational
      analysis, we have tested several force fields and semiempirical parametrizations
      in order to identify those that could be effectively used for modeling of this
      class of compounds. 

PMID- 24866878
TI  - Preimplantation genetic diagnosis for inherited neurological disorders.
AB  - Preimplantation genetic diagnosis (PGD) is an option for couples at risk of
      having offspring with an inherited debilitating or fatal neurological disorder
      who wish to conceive a healthy child. PGD has been carried out for conditions
      with various modes of inheritance, including spinal muscular atrophy, Huntington
      disease, fragile X syndrome, and chromosomal or mitochondrial disorders, and for
      susceptibility genes for cancers with nervous system involvement. Most couples at
      risk of transmitting a genetic mutation would opt for PGD over prenatal testing
      and possible termination of a pregnancy. The aim of this Perspectives article is
      to assist neurologists in counselling and treating patients who wish to explore
      the option of PGD to enable conception of an unaffected child. PGD can be
      accomplished for most disorders in which the genetic basis is known, and we argue
      that it is time for clinicians and neurological societies to consider the
      evidence and to formulate guidelines for the responsible integration of PGD into
      modern preventative neurology.

PMID- 24866887
TI  - Study of the molecular variation in pre-eclampsia placenta based on micro-Raman
      spectroscopy.
AB  - PURPOSE: Study of the molecular variation in pre-eclampsia placenta based on
      micro-Raman spectroscopy. METHODS: Five pregnant women with pre-eclampsia from
      Nanfang hospital were selected as study group whose average age is 28.5 years and
      38 +/- 2 weeks gestation. The same period of healthy pregnant women, whose
      average age is 27.6 years and pregnant 39 +/- 1 weeks, as control group (n = 5).
      The normal and pre-eclamptic placental tissues are detected by micro-Raman
      spectroscopy with the spectrum resolution of 1 cm(-1). RESULTS: We find that the
      protein structure of alpha-helix, beta-pleated sheet and beta-turn is overlying
      in pre-eclamptic placenta, which lead to a disorder of protein structure. The
      Raman peaks assigned to tryptophan indole ring and phenylalanine in pre-eclamptic
      placental tissue are more higher than that in normal tissue. CONCLUSIONS: Results
      suggest that the ordered structures of the main chain in protein molecules are
      reduced significantly, and the amino acid of side chains is damaged obviously.
      And a principal component analysis is used to classify the Raman spectra between
      normal and pre-eclamptic placental tissues. This study presents that Raman
      spectroscopy has a great potential on the mechanism research and diagnosis of
      placental lesions.

PMID- 24866888
TI  - Clinical characteristics and treatment of Herlyn-Werner-Wunderlich syndrome.
AB  - OBJECTIVE: To investigate the clinical characteristics and treatment of the
      Herlyn-Werner-Wunderlich syndrome (HWWS). METHODS: Sixty-one patients diagnosed
      with HWWS were retrospectively analyzed. HWWS is categorized into three types in
      China. RESULTS: Age at presentation of all the cases was after menarche. The most
      common clinical presentations were dysmenorrhea for type I and vaginal discharge
      for types II and III. Clinical presentations of types II and III may not occur
      until reproductive age. HWWS occurred on the right in 39/61. Excision of the
      obstructed vaginal septum was the treatment utilized in this cohort. After
      surgery, subsequent pregnancies were ipsilateral in 52.9 %. CONCLUSIONS: Clinical
      presentation in untreated HWWS suggests the anatomic anomaly. Early recognition
      and treatment can reduce symptoms. Pregnancies occur in both the affected and
      unaffected uterus.

PMID- 24866891
TI  - Relationship Between the Risk of Suffering a First-Time Noncontact ACL Injury and
      Geometry of the Femoral Notch and ACL: A Prospective Cohort Study With a Nested
      Case-Control Analysis.
AB  - BACKGROUND: The morphometric characteristics of the anterior cruciate ligament
      (ACL) and the femoral intercondylar notch within which it resides have been
      implicated as risk factors for injuries to this important stabilizer of the knee.
      Prior research has produced equivocal results with differing methodologies, and
      consequently, it is unclear how these characteristics affect the injury risk in
      male and female patients. HYPOTHESIS: The morphometric characteristics of the ACL
      and femoral intercondylar notch are individually and independently associated
      with the risk of suffering a noncontact ACL injury, and these relationships are
      different in male and female patients. STUDY DESIGN: Case-control study; Level of
      evidence, 3. METHODS: Magnetic resonance imaging scans of the bilateral knees
      were obtained on 88 case-control pairs (27 male, 61 female) matched for age, sex,
      and participation on the same sports team. Patients had suffered a grade III,
      first-time, noncontact ACL tear. The femoral notch width at 4 locations, the
      thickness of the bony ridge at the anteromedial outlet of the femoral notch, the
      femoral notch volume, ACL volume, and ACL cross-sectional area were measured.
      RESULTS: Multivariate analysis of combined data from male and female patients
      revealed that decreased ACL volume (odds ratio [OR], 0.829), decreased femoral
      notch width (OR, 0.700), and increased bony ridge thickness at the anteromedial
      outlet of the femoral notch (OR, 1.614) were significant independent predictors
      of an ACL injury. Separate analyses of male and female patients indicated that
      the femoral notch ridge may be more strongly associated with a risk in female
      patients, while ACL volume is more strongly associated with a risk in male
      patients. However, statistical analysis performed with an adjustment for body
      weight strengthened the association between ACL volume and the risk of injuries
      in female patients. CONCLUSION: Morphometric features of both the ACL and femoral
      notch combine to influence the risk of suffering a noncontact ACL injury. When
      included together in a multivariate model that adjusts for body weight, the
      effects of the morphometric measurements are similar in male and female patients.
      If body weight is not taken into consideration, ACL volume is not associated with
      a risk in female patients.

PMID- 24866892
TI  - Chondroprotection and the prevention of osteoarthritis progression of the knee: a
      systematic review of treatment agents.
AB  - BACKGROUND: Structure-modifying medications or nutraceuticals may be an effective
      treatment for osteoarthritis. This study identified 12 treatments that may
      possess chondroprotective properties: oral glucosamine; chondroitin; nonsteroidal
      anti-inflammatory drugs (NSAIDs); polyunsaturated fatty acids; S
      adenosylmethionine; avocado and soybean unsaponifiable fractions;
      methylsulfonylmethane; vitamins C, D, and E; intra-articular injections of
      hyaluronic acid; and platelet-rich plasma (PRP). PURPOSE: To perform a systematic
      review of randomized controlled trials for the effectiveness of each agent in
      preserving articular cartilage of the knee and delaying the progression of
      osteoarthritis. STUDY DESIGN: Systematic review; Level of evidence, 2. METHODS: A
      literature search was performed using PubMed, EMBASE, and the Cochrane Central
      Register of Controlled Trials. Searches were performed using "treatment,"
      "osteoarthritis," and "knee" as keywords. Selection criteria included randomized
      controlled trials of >=12 months, with a placebo control, measuring radiographic
      changes in joint space width, cartilage volume, or radiographic progression of
      osteoarthritis. The primary outcome was changes in joint integrity measures.
      RESULTS: A total of 3514 studies were identified from the initial search, 13 of
      which met inclusion criteria. Treatment with chondroitin sulfate showed a
      significant reduction in cartilage loss in 3 of 4 studies identified compared
      with placebo. Two of 3 trials identified for glucosamine also reported
      significant structural effects relative to placebo. Intra-articular hyaluronic
      acid was effective in lowering the rate of cartilage loss in only 1 of 3 studies
      identified versus placebo. Of the 6 studies identified for NSAIDs, vitamin E, and
      vitamin D, none showed any structural effect compared with placebo. No studies
      were found that met the inclusion criteria for polyunsaturated fatty acids, S
      adenosylmethionine, avocado and soybean unsaponifiable fractions,
      methylsulfonylmethane, vitamin C, or PRP. CONCLUSION: For patients with or at
      risk for osteoarthritis, the use of glucosamine and chondroitin sulfate may serve
      as a nonoperative means to protect joint cartilage and delay osteoarthritis
      progression. Hyaluronic acid injections showed variable efficacy, while NSAIDs
      and vitamins E and D showed no effect on osteoarthritis progression. The other
      agents evaluated had no evidence in the literature to support or refute their use
      for chondroprotection.

PMID- 24866894
TI  - Dexmedetomidine could enhance surgical satisfaction in Trans-sphenoidal resection
      of pituitary adenoma.
AB  - BACKGROUND: Excessive bleeding is an unwanted complication of trans-sphenoidal
      resection of pituitary adenoma due to increases in intracranial pressure (ICP)
      and hemodynamic instability. Dexmedetomidine (Dex) analpha2-agonists is the drug
      of choice in intensive care units (ICU) and cardiac surgeries to control abrupt
      changes in hemodynamic. Severe cardiovascular responses occur during trans
      sphenoidal resection (TSR) of the pituitary adenoma despite adequate depth of
      anesthesia. The aim of this paper was to determine the effect of Dexmedetomidine
      on bleeding as primary outcome, and surgeon's satisfaction and hemodynamic
      stability as secondary outcomes in patients undergoing trans-sphenoidal resection
      of pituitary adenoma. METHODS: Total numbers of 60 patients between 18-65 years
      old and candidate for elective trans-sphenoidal resection of pituitary adenoma
      were randomLy allocated to two groups; Dexmedetomidine infusion (0.6ug/kg/hour)
      or normal saline infusion. Mean arterial pressure (MAP), heart rate (HR), dose of
      hypnotics and narcotics during surgery, bleeding, and surgeon's satisfaction were
      recorded. RESULTS: Propofol maintenance dose (ug/kg/min) and total Fentanyl use
      (ug) were significantly lower in Dex group compare to control group (P=0.01 and
      0.003, respectively). Total bleeding amount during operation in Dex group was
      significantly lower than control group (P=0.012). Surgeon's satisfaction was
      significantly higher in Dex group at the end of surgery. MAP and heart rate
      throughout surgery were significantly lower in Dex group compare to control group
      (P=0.001). CONCLUSIONS: Dexmedetomidine infusion (0.6ug/kg/hour) could reduce
      bleeding and provide surgeon's satisfaction during trans-sphenoidal resection of
      pituitary adenoma.

PMID- 24866895
TI  - Classification of insular-basal ganglia gliomas based on the displacement of
      corticospinal tracts evaluated by diffusion tensor imaging.
AB  - BACKGROUND: Resection of insula-basal ganglia (IBG) gliomas is challenging
      because of their deep location and vicinity to critical structures, whereas
      diffusion tensor tractography (DTT) can noninvasively delineate the tracks of
      white matter fibers. This study aims to evaluate the role of cortico-spinal tract
      (CST) positions in prediction of the prognosis of patients with IBG gliomas.
      METHODS: We retrospectively reviewed 34 patients with IBG gliomas. DTT was used
      to reconstruct the CSTs for all patients, and the IBG gliomas were classified
      into three types (type I-III) based on the shifted patterns of the CSTs. RESULTS:
      The number of patients with type I IBG gliomas was 12 (35.3%), which was equal to
      the number of patients with type II IBG gliomas, and 10 cases (29.4%) presented
      with type III IBG gliomas. The six-month KPS score was significantly lower in the
      type III IBG group than that in the type I group (t=-11.43, P=0.013) and the type
      II group (t=-9.97, P=0.033). Postoperative MRI demonstrated that gross total or
      near total resection was achieved in 76.5% (26 cases) of all of the patients.
      CONCLUSIONS: The results suggest that the proposed classification of IBG gliomas
      can be used for predicting the long-term postoperative outcome profiles of IBG
      glioma patients.

PMID- 24866893
TI  - The mTOR inhibitor rapamycin synergizes with a fatty acid synthase inhibitor to
      induce cytotoxicity in ER/HER2-positive breast cancer cells.
AB  - Patients with ER/HER2-positive breast cancer have a poor prognosis and are less
      responsive to selective estrogen receptor modulators; this is presumably due to
      the crosstalk between ER and HER2. Fatty acid synthase (FASN) is essential for
      the survival and maintenance of the malignant phenotype of breast cancer cells.
      An intimate relationship exists between FASN, ER and HER2. We hypothesized that
      FASN may be the downstream effector underlying ER/HER2 crosstalk through the
      PI3K/AKT/mTOR pathway in ER/HER2-positive breast cancer. The present study
      implicated the PI3K/AKT/mTOR pathway in the regulation of FASN expression in
      ER/HER2-positive breast cancer cells and demonstrated that rapamycin, an mTOR
      inhibitor, inhibited FASN expression. Cerulenin, a FASN inhibitor, synergized
      with rapamycin to induce apoptosis and inhibit cell migration and tumorigenesis
      in ER/HER2-positive breast cancer cells. Our findings suggest that inhibiting the
      mTOR-FASN axis is a promising new strategy for treating ER/HER2-positive breast
      cancer. 

PMID- 24866897
TI  - Coronary sinus atrial communication in a 58 year old.

PMID- 24866898
TI  - Pseudoaneurysm of the non-coronary sinus of Valsalva mimicking an interatrial
      septal mass.

PMID- 24866899
TI  - Conventional surgery and transcatheter closure via surgical transapical approach
      for paravalvular leak repair in high-risk patients: results from a single-centre
      experience.
AB  - OBJECTIVES: Paravalvular leaks (PVL) occur in up to 17% of all surgically
      implanted prosthetic valves. Re-operation is associated with high morbidity and
      mortality. Transcatheter closure via a surgical transapical approach (TAp) is an
      emerging alternative for selected high-risk patients with PVL. The aim of this
      study was to compare the in-hospital outcomes of patients who underwent surgery
      and TA-closure for PVL in our single-centre experience. METHODS: From October
      2000 to June 2013, 139 patients with PVL were treated in our Institution. All the
      TA procedures were performed under general anaesthesia in a hybrid operative
      room: in all but one case an Amplatzer Vascular Plug III device was utilized.
      RESULTS: Hundred and thirty-nine patients with PVL were treated: 122 patients
      (87.3%) underwent surgical treatment (68% mitral PVL; 32% aortic PVL) and 17
      patients (12.2%) underwent a transcatheter closure via a surgical TAp approach
      (all the patients had mitral PVL; one case had combined mitral and aortic PVLs);
      in 35% of surgical patients and in 47% of TAp patients, multiple PVLs were
      present. The mean age was 62.5 +/- 11 years; the Logistic EuroScore was 15.4 +/-
      3. Most of the patients were in New York Heart Association (NYHA) functional
      class III-IV (57%). Symptomatic haemolysis was present in 35% of the patients,
      and it was particularly frequent in the TAp (70%). Many patients had >1 previous
      cardiac operation (46% overall and 82% of TAp patients were at their second of re
      operation). Acute procedural success was 98%. In-hospital mortality was 9.3%; no
      in-hospital deaths occurred in patients treated through a TAp approach. All the
      patients had less than moderate residual valve regurgitation after the procedure.
      Surgical treatment was identified as a risk factor for in-hospital death at
      univariate analysis (OR: 8, 95% CI: 1.8-13; P = 0.05). Overall actuarial survival
      at follow-up was 39.8 +/- 7% at 12 years and it was reduced in patients who had
      >1 cardiac re-operation (42 +/- 8 vs. 63 +/- 6% at 9 years; P = 0.009).
      CONCLUSIONS: A transcatheter closure via a surgical TAp approach appears to be a
      safe and effective therapeutic option in selected high-risk patients with PVL and
      is associated with a lower hospital mortality than surgical treatment, in spite
      of higher predicted risk. Long-term survival remains suboptimal in these
      challenging patients.

PMID- 24866901
TI  - Pectus excavatum as an unexpected cause for typical cardiologic signs revealed at
      imaging.

PMID- 24866900
TI  - Early systolic lengthening may identify minimal myocardial damage in patients
      with non-ST-elevation acute coronary syndrome.
AB  - AIMS: Ischaemic myocardial segments tend to stretch as the intraventricular
      pressure rises steeply during the isovolemic contraction phase, before they
      contract during ejection. We hypothesized that the time they remain stretched,
      called duration of early systolic lengthening (DESL), correlates with final
      infarct size as defined by contrast enhanced magnetic resonance imaging (CE-MRI).
      We also assessed whether DESL could identify patients with acute coronary
      occlusion, and compared it with traditional measures for myocardial function.
      METHODS AND RESULTS: In this retrospective study, 150 consecutive patients with
      Non-ST-elevation acute coronary syndrome (NSTE-ACS) referred for coronary
      angiography were included. Speckle tracking echocardiography was performed prior
      to angiography to determine DESL. The final infarct size was quantified at follow
      up 9 +/- 3 months after initial admission in 61 patients and echocardiography
      performed in 143 patients. DESL showed good correlation with the final infarct
      size (r = 0.67, P < 0.001). Thirteen patients had no visible sign of infarct on
      CE-MRI (minimal myocardial damage), and DESL was significantly shorter in these
      patients than in patients with signs of infarct (27 +/- 19 vs. 84 +/- 41 ms, P <
      0.001). Compared with left ventricular ejection fraction, wall motion score
      index, and global longitudinal strain, DESL showed the best accuracy in detecting
      patients with minimal myocardial damage, with an area under the receiver
      operating characteristic curve of 0.92 (0.82 to 0.99, P < 0.001). DESL was more
      prolonged in patients with coronary occlusions, compared with those without
      occlusions (86 +/- 45 vs. 63 +/- 31 ms, P < 0.01). DESL was significantly shorter
      at follow-up, compared with baseline (P = 0.04). CONCLUSIONS: DESL could identify
      patients with minimal myocardial damage, differentiate between occlusion and non
      occlusion, and may be helpful in the risk stratification of patients with NSTE
      ACS.

PMID- 24866902
TI  - Focus cardiac ultrasound: the European Association of Cardiovascular Imaging
      viewpoint.
AB  - The concept of point-of-care, problem-oriented focus cardiac ultrasound
      examination (FoCUS) is increasingly applied in the settings of medical
      emergencies, including cardiac diseases. The European Association of
      Cardiovascular Imaging (EACVI) recognizes that cardiologists are not the only
      medical professionals dealing with cardiovascular emergencies. In reality,
      emergency cardiac diagnostics and treatment are also carried out by a wide range
      of specialists. For the benefit of the patients, the EACVI encourages any medical
      professional, sufficiently trained to obtain valuable information from FoCUS, to
      use it in emergency settings. These medical professionals need to have the
      necessary knowledge to understand the obtained information entirely, and to use
      it correctly, thoughtfully and with care. In this document, the EACVI underlines
      major differences between echocardiography and FoCUS, and underscores the need
      for specific education and training in order to fully utilize advantages and
      minimize drawbacks of this type of cardiac ultrasound examination in the
      critically ill patients. 

PMID- 24866903
TI  - Echocardiographic detection of myocardial crypts in hypertrophic cardiomyopathy:
      a first report in phenotype-positive patient.

PMID- 24866905
TI  - Modeling the overall survival of patients with advanced-stage non-small cell lung
      cancer using data of routine laboratory tests.
AB  - Cancer patients undergo routine clinical monitoring with an array of blood tests
      that may carry long-term prognostic information. We aimed to develop a new
      prognostic model predicting survival for patients with advanced non-small cell
      lung cancer (NSCLC), based on laboratory tests commonly performed in clinical
      practice. A cohort of 1,161 stage IIIB or IV NSCLC patients was divided into
      training (n = 773) and testing (n = 388) cohorts. We analyzed the associations of
      32 commonly tested laboratory variables with patient survival in the training
      cohort. We developed a model based on those significant laboratory variables,
      together with important clinical variables. The model was then evaluated in the
      testing cohort. Five variables, including albumin, total protein, alkaline
      phosphatase, blood urea nitrogen and international normalized ratio, were
      significantly associated with patient survival after stepwise selection. A model
      incorporating these variables classified patients into low-, medium- and high
      risk groups with median survival of 16.9, 7.2 and 2.1 months, respectively (p <
      0.0001). Compared with low-risk group, patients in the medium- and high-risk
      groups had a significantly higher risk of death at 1 year, with hazard ratio (HR)
      of 1.95 (95% CI 1.62-2.36) and 5.22 (4.30-6.34), respectively. These results were
      validated in the testing cohort. Overall, we developed a prognostic model relying
      entirely on readily available variables, with similar predictive power to those
      which depend on more specialized and expensive molecular assays. Further study is
      necessary to validate and further refine this model, and compare its performance
      to models based on more specialized and expensive testing.

PMID- 24866906
TI  - A biomechanical study to evaluate the effect of PMMA augmentation and restoration
      of the strength of cervical vertebral screws inserted in an osteoporotic
      vertebral body.
AB  - STUDY DESIGN: An experimental study. OBJECTIVE: To compare the peak pull-out
      force (PPF) of vertebral screws fixed in osteoporotic vertebrae versus
      polymethylmethacrylate (PMMA) used for augmentation or restoration, before and
      after fatigue. SUMMARY OF BACKGROUND DATA: Failure of screw fixation in anterior
      cervical interbody fusion remains a significant clinical problem. However, little
      is known of the biomechanical characteristics of cervical vertebral screws before
      and after restoration or augmentation, especially after fatigue. METHODS: Fifty
      fresh cervical vertebrae, of which 40 were randomly selected, from 12 adult
      cadavers were used. The vertebrae were divided into healthy controls,
      osteoporotic controls, a PMMA restoration group, and a PMMA augmentation group.
      In each of the control groups, 2 pilot holes on each side of 20 vertebral bodies
      were implanted with vertebral screws (4 mm in diameter). Each side randomly
      received either acute PPF or PPF beyond fatigue that was ensured using cyclic
      loading (2 Hz; 20,000 times). In the PMMA groups, pilot holes were drilled
      parallel to the sagittal plane and injected with 0.6-1.0 mL PMMA before the
      vertebral screw was inserted. Each side of each vertebral body randomly received
      either PPF or PPF beyond fatigue that was ensured using cyclic loading (2 Hz;
      20,000 times). A Bose3510-AT fatigue testing machine measured the PPF of
      vertebral screws with or without PMMA for all specimens before and after fatigue.
      RESULTS: In all groups, the prefatigue PPF was significantly higher than the
      postfatigue PPF. Compared with the prefatigue PPF, postfatigue PPF was reduced by
      37.40%, 43.10%, 32.08%, and 31.85% in the healthy controls, osteoporotic
      controls, PMMA restoration, and PMMA augmentation groups, respectively. The acute
      and postfatigue PPFs of the healthy controls were significantly higher from that
      of the osteoporotic controls. The acute and postfatigue PPFs of both control
      groups were significantly lower from that of both PMMA groups. There was no
      difference in acute and postfatigue PPFs between the PMMA restoration and
      augmentation groups. CONCLUSIONS: The results indicated that both PMMA
      augmentation and PMMA restoration could significantly increase cervical screw
      pull-out strength and antifatigue capability. The results provide a biomechanical
      justification for spine surgeons to use PMMA for augmentation or restoration in
      cases of surgeries with poor bone quality or osteoporotic vertebral bodies.

PMID- 24866907
TI  - Occipitocervical fusion via occipital condylar fixation: a clinical case series.
AB  - STUDY DESIGN: Retrospective review/case series. OBJECTIVE: This study aims to
      present the clinical feasibility of condylar fixation in occipitocervical (OC)
      fusion. Here, we present the largest clinical series to date of patients who
      underwent OC fusion via cervicocondylar fixation using a polyaxial screw/rod
      construct. SUMMARY OF BACKGROUND DATA: The novel technique using the occipital
      condyles as the sole cranial fixation point has been described. Both cadaveric
      and biomechanical studies, in recent literature, have shown technical feasibility
      and surgical safety of condylar fixation. METHODS: We retrospectively reviewed a
      prospectively acquired database of all patients treated with OC fusion via
      cervicocondylar fixation at our institution between 2007 and 2011. All patients
      were scheduled for follow-up postoperatively at weeks 2, 6, 12, 24, and annually
      thereafter. Outcome measures included estimated blood loss, operative time,
      complications, integrity of the construct, and fusion rates. Exclusion criteria
      included condylar fracture, previous cervical fusion, or vertebral artery injury.
      Enrolled patients subsequently underwent posterior OC fixation using occipital
      condyle, C1 lateral mass, and/or C2 pars interarticularis screw fixation.
      Subaxial cervical fixation consisted of lateral mass screw placement.
      Intraoperative fluoroscopy and hypoglossal monitoring were used. RESULTS: We
      identified 12 consecutive patients who underwent OC fusion using the occipital
      condyle as the cranial fixation point using polyaxial screws. The mean operative
      time was 283 minutes (192-416). The mean total blood loss was 229 mL (100-400).
      Mean follow-up was 21.4 months (4-39). One patient suffered from a superficial
      wound infection. There were no neural or vascular complications. Radiographic
      evidence of OC fusion was noted for all patients with >6-month follow-up.
      CONCLUSIONS: OC fusion using occipital condylar screws is a feasible alternative
      to current occipital plate fixation. Condylar screw fixation can be performed
      safely with successful arthrodesis as a treatment for OC instability in patients.

PMID- 24866909
TI  - Effects of repeated administration of methylphenidate on reproductive parameters
      in male rats.
AB  - Methylphenidate (MPH) is a psychostimulant drug which acts by blocking the
      dopamine and norepinephrine transporters and is the main drug used to treat
      attention deficit hyperactivity disorder in children and adolescents. During
      puberty, changes in neurotransmitter systems (including dopaminergic system) are
      engaged on the release of gonadal hormones and the development of cephalic
      structures responsible for reproductive function. This study investigated the
      effects of repeated treatment with methylphenidate during development on
      reproductive parameters of adult male rats. Wistar rats received MPH 2.5 mg/kg,
      MPH 5.0 mg/kg, or distilled water (gavage) from postnatal day (PND) 21 to PND 60.
      At PND 100, an increase in percentage of abnormal tail morphology sperm in MPH
      2.5 and increase in testicular interstitial tissue volume in MPH groups as well
      as in the number of type A spermatogonia in MPH 5.0 group were observed. This
      study demonstrated that repeated administration of methylphenidate during periods
      corresponding childhood to early adulthood interfered on testicular function in
      rats at adult life.

PMID- 24866908
TI  - Clinical application of computer-aided design-rapid prototyping in C1-C2
      operation techniques for complex atlantoaxial instability.
AB  - STUDY DESIGN: This is a retrospective clinical study. OBJECTIVE: To evaluate the
      clinical efficacy of computer-aided design-rapid prototyping (CAD-RP) techniques
      in surgical treatments for atlantoaxial instability (AAI). SUMMARY OF BACKGROUND
      DATA: The complexity of the upper cervical anatomic structures makes the
      procedures for the treatment of AAI particularly challenging for surgeons. The
      present study represents a series of C1-C2 surgery for AAI aided by CAD-RP.
      METHODS: A total of 49 patients (21 men and 28 women) with AAI were treated in
      our department. According to the use of the CAD-RP technique, the patients were
      divided into RP group and No RP group. Preoperative CT scans of the upper
      cervical spine were performed for each patient. For the RP group, physical RP
      models of the upper cervical spine were manufactured from the 3-dimensional CT
      data and were used for intraoperative guidance. Personalized surgeries were
      performed for each case of the 2 groups. The screw malposition rate, frequency of
      using intraoperative fluoroscopy, operation time, blood loss, and improvement of
      neurological function were compared between the 2 groups. The mean follow-up
      duration was 32 months (range, 24-50 mo). RESULTS: The operations were
      successfully performed in 48 cases expect for 1 case in the No RP group. A total
      of 204 screws were placed. The intraoperative fluoroscopy frequency and operation
      time were significantly lower in the RP group than that in the No RP group in
      both posterior and anterior approaches, whereas the screw malposition rate showed
      no difference between the 2 groups for both approaches. After the operation, 48
      cases achieved satisfactory decompression of the cervical cord and repositioning
      of the atlantoaxial spine. During follow-up, 47 cases presented improvements in
      the spinal nerve function within 2 years. CONCLUSIONS: CAD-RP techniques have
      significant benefits for surgeons providing personalized treatments for AAI,
      especially cases with complicated deformities.

PMID- 24866910
TI  - Experimental manipulation of breakfast in normal and overweight/obese
      participants is associated with changes to nutrient and energy intake consumption
      patterns.
AB  - The effect of breakfast and breakfast omission on daily food intake in normal and
      overweight participants was investigated. 37 participants were recruited for this
      experimental study and assigned to one of four groups on the basis of their body
      mass index (BMI) (normal weight BMI <25 kg/m(2) or overweight/obese BMI >25
      kg/m(2)) and breakfast habits (breakfast eater or breakfast omitter). All
      participants were requested to eat breakfast for an entire week, and then
      following a washout period, omit breakfast for an entire week, or vice versa.
      Seven-day food diaries reporting what was consumed and the timing of consumption
      were completed for each breakfast condition. Overall more energy was consumed
      during the breakfast than the no breakfast week. The present study revealed
      significant effects of timing on energy intakes; more energy was consumed during
      the afternoon in the no breakfast week compared to the breakfast week. Overweight
      participants consumed greater amounts of energy than normal weight participants
      in the early evening. Breakfast omitters consumed more than did breakfast eaters
      later in the evening. All groups consumed significantly less energy, carbohydrate
      and fibre in the no breakfast week; however, overweight participants increased
      their sugar intakes. Consumption of the micronutrients iron and folate was
      reduced in the no breakfast week. The findings highlight that the timing of food
      intake and habitual breakfast eating behaviour are important factors when
      investigating why breakfast consumption may be associated with BMI.

PMID- 24866912
TI  - Physiological, physical and behavioural changes in dogs (Canis familiaris) when
      kennelled: testing the validity of stress parameters.
AB  - Domestic dogs (Canis familiaris) housed in kennelling establishments are
      considered at risk of suffering poor welfare. Previous research supporting this
      hypothesis has typically used cortisol:creatinine ratios (C/Cr) to measure acute
      and chronic stress in kennelled dogs. However, the value of C/Cr as a welfare
      indicator has been questioned. This study aimed to test the validity of a range
      of physiological, physical and behavioural welfare indicators and to establish
      baseline values reflecting good dog welfare. Measurements were taken from 29
      privately-owned dogs (14 males, 15 females), ranging in age and breed, in their
      own home and in a boarding kennel environment, following a within-subjects,
      counterbalanced design. Pairwise comparisons revealed that C/Cr and
      vanillylmandelic acid:creatinine ratios (VMA/Cr) were higher in the kennel than
      home environment (P=0.003; P=0.01, respectively) and were not associated with
      differences in movement/exercise between environments. Dogs' surface temperature
      was lower in kennels (P=0.001) and was not associated with ambient temperature.
      No association with age, or effects of kennel establishment, kennelling
      experience, sex or source were found. Dogs were generally more active in kennels,
      but showed considerable individual variability. C/Cr and 5-HIAA:creatinine ratios
      (5-HIAA/Cr) were negatively correlated with lip licking in kennels. Baseline
      values for each parameter are presented. The emotional valence of responses was
      ambiguous and no definitive evidence was found to suggest that dogs were
      negatively stressed by kennelling. It was concluded that C/Cr and, particularly,
      VMA/Cr and surface temperature provide robust indicators of psychological arousal
      in dogs, while spontaneous behaviour might be better used to facilitate
      interpretation of physiological and physical data on an individual level. 

PMID- 24866911
TI  - Female-biased anorexia and anxiety in the Syrian hamster.
AB  - Anorexia and anxiety cause significant mortality and disability with female
      biases and frequent comorbidity after puberty, but the scarcity of suitable
      animal models impedes understanding of their biological underpinnings. It is
      reported here that in adult or weanling Syrian hamsters, relative to social
      housing (SH), social separation (SS) induced anorexia characterized as
      hypophagia, weight loss, reduced adiposity, and hypermetabolism. Following
      anorexia, SS increased reluctance to feed, and thigmotaxis, in anxiogenic
      environments. Importantly, anorexia and anxiety were induced post-puberty with
      female biases. SS also reduced hypothalamic corticotrophin-releasing factor mRNA
      and serum corticosteroid levels assessed by RT-PCR and RIA, respectively.
      Consistent with the view that sex differences in adrenal suppression contributed
      to female biases in anorexia and anxiety by disinhibiting neuroimmune activity,
      SS elevated hypothalamic interleukin-6 and toll-like receptor 4 mRNA levels.
      Although corticosteroids were highest during SH, they were within the
      physiological range and associated with juvenile-like growth of white adipose,
      bone, and skeletal muscle. These results suggest that hamsters exhibit plasticity
      in bioenergetic and emotional phenotypes across puberty without an increase in
      stress responsiveness. Thus, social separation of hamsters provides a model of
      sex differences in anorexia and anxiety during adulthood and their pathogeneses
      during adolescence. 

PMID- 24866913
TI  - Physiology of aqueous humor dynamic in the anterior chamber due to rapid eye
      movement.
AB  - The nature of aqueous humor (AH) mixing in the anterior chamber (AC) of the human
      eye due to rapid eye movement (REM) has not been fully understood and has been
      somewhat a controversial issue. This study uses a computational modeling approach
      to shed light on this issue. For this purpose a numerical method was developed
      and used to solve the mathematical equations governing the flow and mixing of
      aqueous humor motion in the eye subjected to such movements. Based on the
      experimental measurements available in the literature for the average and maximum
      amplitudes of the eye movements, a harmonic model for the REM was developed. The
      corresponding instantaneous and time-averaged velocity fields were evaluated. The
      simulation results showed that, contrary to earlier reports, the REM led to
      complex flow structures and a 3-D mixing of AH in the anterior chamber. In
      addition, the mixing velocity increased in direct proportion to the REM
      amplitudes. Thus, the AC flow generated by REM could carry nutrients to the
      posterior surface of the cornea during the sleep. Furthermore, the shear stress
      acting on the corneal endothelial cells due to REM was computed and compared with
      that of buoyancy driven flow in the AC due to temperature gradient. It was found
      that the shear stress generated by REM is much higher than that introduced by the
      natural convection. A video file for providing a better understanding of the AH
      mixing process in the AC was also prepared. This video is available on the web. 

PMID- 24866914
TI  - An efficient catalytic system based on 7,8-dihydroxy-4-methylcoumarin and
      copper(II) for the click synthesis of diverse 1,4-disubstituted-1,2,3-triazoles
      under green conditions.
AB  - In this work, the combination of 7,8-dihydroxy-4-methyl coumarin (DHMC) as a
      novel bidentate O,O-chelating agent and copper(II) acetate monohydrate (2:1 molar
      ratio) has been found to form an efficient catalytic system. This catalyst
      provided good to excellent yields in the multi-component click synthesis of 1,4
      disubstituted-1,2,3-triazoles by using various structurally diverse organic
      halides, different non-activated terminal alkynes, and sodium azide. This
      catalytic system eliminates the need for the isolation of the hazardous azide
      intermediates which are generated in situ. The reaction is carried out in aqueous
      phase at room temperature and it can be accelerated by sonication or by
      increasing the reaction temperature. Moreover, the reaction can be performed in
      large scale. It is noteworthy that DHMC is commercially available and that it can
      be easily synthesized with low cost materials. 

PMID- 24866915
TI  - An unfortunate experiment? The future of ethical review in New Zealand.
AB  - This report describes the system of ethical review that was adopted in New
      Zealand based on the findings and recommendations from the Cartwright Inquiry in
      1988. It discusses the changes made to this system under recent governmental
      initiatives enacted by the National Party, and some of the implications of those
      changes.

PMID- 24866918
TI  - Prevalence of temporomandibular dysfunction and pain in adult general practice
      patients.
AB  - OBJECTIVE: To analyse the prevalence of temporomandibular disorders and related
      pain (TMD-pain) among adult recall patients in general dental practice. MATERIALS
      AND METHODS: From November 2006 to September 2008, all adults attending a Swedish
      Public Dental Service (PDS) clinic for recall examination were asked two
      standardized questions about temporomandibular pain and dysfunction. Mouth
      opening capacity was measured. The responses to the questions and mouth-opening
      capacity were combined to give a TMD-pain score, on a scale of 0-3. The patients'
      acceptance of their TMD condition was also noted. RESULTS: The subjects comprised
      2837 adults (53% females, 47% men). Of the total sample, 4.9% reported a TMD-pain
      score of 1-3. The gender difference was significant: women predominated (p <
      0.003). Forty-three per cent of those with TMD-pain scores of 1-3 (36% men, 47%
      women) considered that the condition warranted treatment, especially those
      registering a pain score (significant difference between pain and dysfunction
      groups, p < 0.000). CONCLUSIONS: The TMD-pain score shows promise as a useful
      instrument for detecting and recording TMD-pain. The prevalence of TMD disclosed
      in the study is high enough to be considered a public health concern. Most of the
      subjects with lower scores on the TMD-pain scale accepted their condition as not
      severe enough to require treatment.

PMID- 24866916
TI  - Connexin31.1 (Gjb5) deficiency blocks trophoblast stem cell differentiation and
      delays placental development.
AB  - The gap junction channel forming connexins (Cx) Cx31 (Gjb3) and Cx31.1 (Gjb5) are
      co-expressed in the mouse trophoblast lineage. Inactivation of either gene
      results in partial embryonic loss at mid gestation (60% and 30%, respectively,
      between embryonic days E10.5and E13.5) caused by placental phenotypes. Cx31
      deficiency results in loss of stem cell potential and enhanced trophoblast giant
      cell (TGC) differentiation, whereas the molecular role of the co-expressed Cx31.1
      remained unclear. It was assumed that both isoforms have overlapping functions
      and can compete for each loss in placentation as both knockout mice show similar
      survival rates, reduced placental weights, and growth restricted embryos.
      Instead, here we show that Cx31.1 has opposed functions in regulating trophoblast
      differentiation. Cx31.1 deficiency causes a shift in placental subpopulations,
      reduced area of fetal blood spaces, and a reduced number of secondary TGC in the
      junctional zone, as shown by stereology at E10.5. Cx31.1 is critical for terminal
      differentiation of trophoblast cells during placentation resulting in a delayed
      induction of marker genes Tpbpa, Prl3b1/Pl-2, and Ctsq in Cx31.1-deficient
      placentas. Derivation and analysis of Cx31.1-deficient trophoblast stem lines
      clearly indicates a delayed trophoblast differentiation manifested by repression
      of marker genes for placental subpopulations and continued expression of stem
      cell marker genes Id2 and Ascl2, which is correlated to enhanced proliferation
      capacity of differentiating stem cells These findings clarify the disparate
      actions of Cx31.1 and Cx31 that act in opposition to balance the fate of
      trophoblast cells during differentiation, with Cx31.1 promoting, and Cx31
      delaying terminal differentiation. 

PMID- 24866919
TI  - Degeneration of fungiform and circumvallate papillae following molar extraction
      in rats.
AB  - OBJECTIVE: Proper occlusion facilitates food intake and gustatory function is
      indispensable for the enjoyment of food. Although an interaction between
      dentoalveolar and gustatory afferent neurons has been suggested by previous
      studies, the relationship between occlusion and gustation remains unclear. This
      study investigated the effect of upper molar extraction which diminished occlusal
      support on peripheral gustatory receptors in rats. MATERIALS AND METHODS: Thirty
      six 7-week-old male Wistar rats were randomly assigned to either the experimental
      or the control group. All maxillary molars were extracted from rats in the
      experimental group under anesthesia, while a sham operation was conducted in the
      control group. The rats were euthanized 7, 14 or 28 days after the procedure. The
      morphology of the circumvallate papillae and taste buds using immunohistochemical
      methods and the fungiform papillae were visualized with 1% methylene blue.
      RESULTS: Defects in the gustatory epithelium were observed after maxillary molar
      extraction. Rats in the experimental group had significantly fewer fungiform
      papillae, narrower circumvallate papillae, shallower trench depth, smaller trench
      area, smaller taste bud area, lower ratios of taste bud area to trench area and
      fewer taste buds than those in the control group. CONCLUSIONS: The findings
      indicate that molar extraction would affect peripheral gustatory receptors. This
      is the first study to characterize changes in rat fungiform and circumvallate
      papillae after maxillary molar extraction. This study suggests a possible
      synergic relationship between dentoalveolar perception and gustatory function,
      which has clinical implications that occlusion is closely correlated with
      gustatory perception.

PMID- 24866920
TI  - Matched-names analysis reveals no evidence of name-meaning effects: a
      collaborative commentary on Silberzahn and Uhlmann (2013).

PMID- 24866921
TI  - Misleading first impressions: different for different facial images of the same
      person.
AB  - Studies on first impressions from facial appearance have rapidly proliferated in
      the past decade. Almost all of these studies have relied on a single face image
      per target individual, and differences in impressions have been interpreted as
      originating in stable physiognomic differences between individuals. Here we show
      that images of the same individual can lead to different impressions, with within
      individual image variance comparable to or exceeding between-individuals variance
      for a variety of social judgments (Experiment 1). We further show that
      preferences for images shift as a function of the context (e.g., selecting an
      image for online dating vs. a political campaign; Experiment 2), that preferences
      are predictably biased by the selection of the images (e.g., an image fitting a
      political campaign vs. a randomly selected image; Experiment 3), and that these
      biases are evident after extremely brief (40-ms) presentation of the images
      (Experiment 4). We discuss the implications of these findings for studies on the
      accuracy of first impressions. 

PMID- 24866922
TI  - Endocrine therapy initiation among Medicaid-insured breast cancer survivors with
      hormone receptor-positive tumors.
AB  - PURPOSE: Hormone receptor-positive (HR+) cancers account for most breast cancer
      diagnoses and deaths. Among survivors with HR + breast cancers, endocrine therapy
      (ET) reduces 5-year risk of recurrence by up to 40%. Observational studies in
      Medicare- and privately-insured survivors suggest underutilization of ET. We
      sought to characterize ET use in a low-income Medicaid-insured population in
      North Carolina. METHODS: Medicaid claims data were matched to state cancer
      registry records for survivors aging 18-64 diagnosed with stage 0-II HR + breast
      cancer from 2003 to 2007, eligible for ET, and enrolled in Medicaid for at least
      12 of 15 months post-diagnosis. We used multivariable logistic regression to
      model receipt of any ET medication during 15 months post-diagnosis controlling
      for age, race, tumor characteristics, receipt of other treatments, comorbidity,
      residence, reason for Medicaid eligibility, involvement in the Breast and
      Cervical Cancer Control Program (BCCCP), and diagnosis year. RESULTS: Of 222
      women meeting the inclusion criteria, only 50% filled a prescription for ET.
      Involvement in the BCCCP and earlier year of diagnoses were associated with
      significantly higher odds of initiating guideline-recommended ET (adjusted odds
      ratio [AOR] for the BCCCP 3.76, 95% confidence interval [CI] 1.67-8.48; AOR for
      2004 relative to 2007 2.80, 95% CI 1.03-7.62; AOR for 2005 relative to 2007 2.11,
      95% CI 0.92-4.85). CONCLUSIONS: Results suggest substantial underutilization of
      ET in this population. Interventions are needed to improve timely receipt of ET
      and to better support survivors taking ET. IMPLICATIONS FOR CANCER SURVIVORS: Low
      income survivors should be counseled on the importance of ET and offered support
      services to promote initiation and long-term adherence.

PMID- 24866924
TI  - Elucidating the effect of the nucleophilicity of the silyl group in the reduction
      of CO2 to CO mediated by silyl-copper(I) complexes.
AB  - The reduction of CO2 to CO with silyl-copper(I) complexes bearing various silyl
      groups has been investigated. The silyl-copper(I) complexes [LSi(X)Cu(IPr)] 2-5
      (X = OtBu (2), OH (3), H (4), OC6F5 (5); L = CH{C=CH2}(CMe)(NAr)2, IPr =
      (CHNAr)2C:, Ar = 2,6-iPr2C6H3) bearing OtBu, OH, H, and OC6F5 as functional
      groups are readily accessible by the activation of the Cu-O and Cu-H bonds in
      (IPr)CuX with silylene LSi: (1). These complexes are not readily accessible by
      the commonly used transmetallation reaction, rendering this methodology rather
      unique and facile in synthesizing silicon-functionalized silyl-metal complexes.
      The functional groups at the silicon atoms in compounds 2-5 enable the silyl
      groups to feature different nucleophilicity, which affords different activities
      toward CO2 reduction to CO. The silyl moieties of complexes 2 and 3, containing
      electron-donating groups (i.e., OtBu and OH) at the silicon centers, are more
      nucleophilic than that of compound 4 and 5, bearing a hydride and the electron
      withdrawing group OC6F5 at the silicon centers, respectively. Consistent with
      this observation, compounds 2 and 3 show higher activity in CO2 reduction to CO
      compared to compounds 4 and 5, and the latter cases are zero-order reactions with
      respect to 4 and 5 (4: k = 7.8*10(-6) mol L(-1) s(-1); 5: 2.7*10(-8) mol L(-1) 
      s(-1)). This suggests that the more nucleophilic the silyl moiety in a silyl
      copper(I) complex is, the higher is the efficiency in CO2 reduction to CO. In
      addition, the siloxyl-copper(I) complexes [LSi(X)OCu(IPr)] 6-9 [X = OtBu (6), OH
      (7), H (8), OC6F5 (9)] were isolated as the products from the corresponding
      reduction reactions. Complexes 2-4 and 6-8 were characterized by spectroscopic
      and structural means.

PMID- 24866923
TI  - Survivorship Care Plans to inform the primary care physician: results from the
      ROGY care pragmatic cluster randomized controlled trial.
AB  - PURPOSE: This study assesses the effect of sending a Survivorship Care Plan (SCP)
      to primary care physicians (PCP) on the communication of the PCP with the medical
      specialist and the patient and to describe PCPs' opinions regarding the SCP.
      METHODS: In a pragmatic cluster randomized controlled trial conducted in 12
      hospitals, the PCP of endometrial and ovarian cancer patients received usual
      information, while in addition the SCP-care arm received a copy of the patient's
      SCP. RESULTS: A questionnaire was returned by 266 PCPs (76%). One third of the
      PCPs in the SCP-care arm indicated having received an SCP. PCPs in the SCP-care
      arm were more likely to have had personal contact with the medical specialist (52
      vs. 37%, p = 0.01) but were equally satisfied with the information as PCPs in the
      usual care arm (7.2 vs. 6.9 on a scale from 1 to 10, p = 0.25). Of all PCPs, 82%
      indicated they would want to receive an SCP in the future. A quarter of the PCPs
      who received an SCP reported that the SCP supported contact with the patient.
      However, the SCP was found too long. CONCLUSIONS: Supplying an SCP to PCPs
      potentially has a positive effect on the communication between the PCP and the
      medical specialist. The SCP should be concise and focused on PCPs' needs, such as
      contact information and tailored information on patient diagnosis, treatment, and
      possible consequences. IMPLICATIONS FOR CANCER SURVIVORS: In the light of
      transition of cancer care to PCPs, survivors may benefit from improved
      information provision and communication.

PMID- 24866927
TI  - Electric-field-induced phase separation and homogenization dynamics in colloidal
      suspensions of dichroic rod-shaped pigment particles.
AB  - We report a reversible phase separation phenomenon in nonpolar colloidal
      suspensions of rod-shaped dichroic pigment particles in an electric field. The
      voltage-frequency phase diagram features a variety of phases with different
      morphologies. Single static particle-rich islands, chains of islands, and dynamic
      patterns were found in this system. We demonstrate that those patterns exhibit
      complex relaxation dynamics toward the homogeneous field-free state once the
      external field is removed. 

PMID- 24866926
TI  - Daily physical activity in low-risk extremely low birth weight preterm infants:
      positive impact on bone mineral density and anthropometric measurements.
AB  - The aim of this study was to evaluate the changes in bone mineral density and
      anthropometric indices of extremely low birth weight (ELBW) preterm infants
      undergoing daily physical activity. Twenty-eight low-risk ELBW preterm infants
      (intervention group = 14, control group = 14) with a birth weight of under 1000 g
      and gestational age of 26-32 weeks were recruited. Preterm infants in the control
      group were provided with standard nursing care, whereas those in the intervention
      group received a daily physical activity programme in addition to standard
      nursing care during the study. Before and after the study, anthropometric indices
      and tibial speed of sound (SOS) values were measured. In this study, the tibial
      SOS values were found to be increased in the intervention group (+111.14 m/s) (p
      = 0.001) and decreased in the control group (-58.21 m/s) (p = 0.030). The
      increase in percentage of body weight, height, and tibial length of infants in
      the intervention group was significantly higher than in the control group
      (respectively; p = 0.002, p = 0,015, p < 0.001). A daily physical activity
      programme increased body weight, height, tibial length, and SOS values of the
      tibia in ELBW preterm infants.

PMID- 24866925
TI  - Maternal perception of malnutrition among infants using verbal and pictorial
      methods in Kenya.
AB  - OBJECTIVE: To compare mothers' perceptions of their own infants' nutritional
      status with anthropometric indicators of undernutrition. DESIGN: A qualitative
      study and cross-sectional quantitative survey. The qualitative study involved
      developing tools to assess mother's perception. Two methods of verbal description
      and a pictorial scale were developed. The quantitative survey involved measuring
      maternal perception and comparing it with the anthropometric measures of weight
      for-age Z-score (WAZ) and mid-upper arm circumference-for-age Z-score (MUACZ).
      SETTING: A rural community setting in Kenya. SUBJECTS: Seventy-four infants aged
      between 4 and 6 months, and their mothers, living in rural Kenya were enrolled.
      RESULTS: Using verbal description, the positive and negative likelihood ratios
      were 3.57 (95 % CI 1.44, 9.98) and 0.69 (95 % CI 0.50, 0.96) respectively for
      MUACZ<-2; and 4.60 (95 % CI 1.60, 13.3) and 0.67 (95 % CI 0.49, 0.92)
      respectively for WAZ<-2. Using the pictorial scale, the positive and negative
      likelihood ratios were 8.30 (95 % CI 1.91, 36.3) and 0.69 (95 % CI 0.52, 0.93)
      respectively for MUACZ<-2; and 4.31 (95 % CI 1.22, 15.0) and 0.78 (95 % CI 0.61,
      1.00) respectively for WAZ<-2. CONCLUSIONS: In a rural community, mothers better
      identify undernutrition in their infants using a pictorial scale than verbal
      description. However, neither can replace formal anthropometric assessment.
      Objective anthropometric tools should be validated for identification of severe
      acute malnutrition among infants aged less than 6 months.

PMID- 24866928
TI  - Elucidating the mode of action of a typical Ras state 1(T) inhibitor.
AB  - The small GTPase Ras is an essential component of signal transduction pathways
      within the cell, controlling proliferation, differentiation, and apoptosis. Only
      in the GTP-bound form does Ras interact strongly with effector molecules such as
      Raf-kinase, thus acting as a molecular switch. In the GTP-bound form, Ras exists
      in a dynamic equilibrium between at least two distinct conformational states,
      1(T) and 2(T), offering different functional properties of the protein. Zn2+
      cyclen is a typical state 1(T) inhibitor; i.e., it interacts selectively with Ras
      in conformational state 1(T), a weak effector binding state. Here we report that
      active K-Ras4B, which is prominently found to be mutated in human tumors,
      exhibits a dynamic equilibrium like H-Ras, which can be modulated by Zn2+-cyclen.
      The titration experiments of Ras with Zn2+-cyclen indicate a cooperatively
      coupled binding of the ligands to the two interaction sites on Ras that could be
      identified for H-Ras previously. Our data further indicate that as in state 2(T)
      where induced fit produces the substate 2(T)* after effector binding, a
      corresponding substate 1(T)* can be detected at the state 1(T) mutant Ras(T35A).
      The interaction of Zn2+-cyclen with Ras not only shifts the equilibrium toward
      the weak effector binding state 1(T) but also perturbs the formation of substate
      1(T)*, thus enhancing the inhibitory effect. Although Zn2+-cyclen shows an
      affinity for Ras in only the millimolar range, its potency of inhibition
      corresponds to a competitive state 2 inhibitor with micromolar binding affinity.
      Thus, the results demonstrate the mode of action and potency of this class of
      allosteric Ras inhibitors.

PMID- 24866929
TI  - The role of the different neoglottis forms in the development of esophageal
      voice.
AB  - Evaluation of voice quality parameters of esophageal speech in different
      neoglottis forms after total laryngectomy. METHODS: Presentation of voice
      analysis of 20 patients, who underwent total laryngectomy. The success of
      acquiring this technique was estimated by means of a voice analyzing program
      (pitch, sound-holding, loudness, spectrogram),and by the intelligibility via the
      telephone. Shape of the different types of neoglottis that developed and its
      functioning during vocalization and continuous speech were observed by nasal
      endoscopy. Data obtained from the voice analysis were compared among the observed
      three different neoglottis forms. RESULTS: The average dysphonia index of the 20
      patients was 1.67 +/- 0.38 (mean +/- SD). Nasal fiberoscopic examination revealed
      three different types of neoglottis forms - a small mucosal button, two mucosal
      battens, and a mucosal lip. Voice quality of the esophageal speech of the
      patients with the mucosal button was found to be the closest to normal by
      subjective and objective acoustical evaluation. CONCLUSIONS: These findings
      emphasize the importance of the proper wound closure technique which can
      facilitate the development of a special button shape neoglottis form and help to
      acquire esophageal speech with the best quality parameters shortly after total
      laryngectomy.

PMID- 24866930
TI  - Effect of N-methyl-D-aspartic acid on activity of superoxide dismutase, catalase,
      glutathione peroxidase and reduced glutathione level in selected organs of the
      mouse.
AB  - One of the major classes of ionotropic glutamate receptors is the class of N
      methyl-D-aspartate receptors (NMDARs). Receptor activation recruits, via calcium
      signal transduction mechanisms which play important roles in oxidative
      metabolism, mitochondrial free radical production and occurrence of other
      mitochondrial factors which potentially contribute to excitotoxicity and neuronal
      death. In the present study, the effects of stimulation of NMDARs by applying N
      methyl-D-aspartic acid (NMDA) in the brain, liver, kidneys and pancreas on change
      of the activity of superoxide dismutase (SOD), catalase (CAT) and glutathione
      peroxidase (GSHPx) and in the amount of reduced glutathione (GSH) in blood,
      brain, liver and kidneys has been investigated. Statistically significant
      decrease of the activity of SOD, CAT and GSHPx and in the amount of reduced
      glutathione (GSH) was found in the examined organs after administration of NMDA,
      an agonist of NMDA receptors, demonstrating that NMDA administration compromises
      the antioxidant status in the investigated organs of the mouse. 

PMID- 24866931
TI  - An investigation into the accuracy of Acuros(TM) BV in heterogeneous phantoms for
      a (192)Ir HDR source using LiF TLDs.
AB  - The aim of this study was to evaluate the accuracy of the new Acuros(TM) BV
      algorithm using well characterized LiF:Mg,Ti TLD 100 in heterogeneous phantoms.
      TLDs were calibrated using an (192)Ir source and the AAPM TG-43 calculated dose.
      The Tolli and Johansson Large Cavity principle and Modified Bragg Gray principle
      methods confirm the dose calculated by TG-43 at a distance of 5 cm from the
      source to within 4 %. These calibrated TLDs were used to measure the dose in
      heterogeneous phantoms containing air, stainless steel, bone and titanium. The
      TLD results were compared with the AAPM TG-43 calculated dose and the Acuros
      calculated dose. Previous studies by other authors have shown a change in TLD
      response with depth when irradiated with an (192)Ir source. This TLD depth
      dependence was assessed by performing measurements at different depths in a water
      phantom with an (192)Ir source. The variation in the TLD response with depth in a
      water phantom was not found to be statistically significant for the distances
      investigated. The TLDs agreed with Acuros(TM) BV within 1.4 % in the air phantom,
      3.2 % in the stainless steel phantom, 3 % in the bone phantom and 5.1 % in the
      titanium phantom. The TLDs showed a larger discrepancy when compared to TG-43
      with a maximum deviation of 9.3 % in the air phantom, -11.1 % in the stainless
      steel phantom, -14.6 % in the bone phantom and -24.6 % in the titanium phantom.
      The results have shown that Acuros accounts for the heterogeneities investigated
      with a maximum deviation of -5.1 %. The uncertainty associated with the TLDs
      calibrated in the PMMA phantom is +/-8.2 % (2SD). 

PMID- 24866932
TI  - Two new alkaloids from the edible macrofungus Ramaria madagascariensis.
AB  - Phytochemical investigation of the ethyl acetate extract of the edible
      macrofungus, Ramaria madagascariensis, has led to the isolation of two new
      alkaloids (1 and 2). Their structures were elucidated by HR-ESI-MS, IR, and 1D-
      and 2D-NMR experiments. The antimicrobial activity of 1 and 2 was also tested and
      evaluated. 

PMID- 24866933
TI  - Usefulness of myoglobin containing cobalt heme cofactor in designing a myoglobin
      based artificial oxygen carrier.
AB  - The structure and reactivity of cobalt-replaced myoglobin (Mb) were investigated
      to explore its possible application as an artificial oxygen carrier. Ligand
      binding analysis with relaxation kinetics revealed that various ligands bind to
      Co(III) Mb, contrary to the earlier thoughts. The equilibration process, however,
      was so slow that it proceeded over 90 min. These characteristic profiles of
      oxidized Co(III) Mb were ascribed to the electronic structure of Co(III) ion
      which is one electron larger than Fe(III) ion. The oxygen affinity of reduced
      Co(II) Mb was much smaller than that of Fe(II) Mb indicating that Co(II) Mb has
      excellent oxygen transport ability. The latter observation, together with the
      lack of carbon monoxide binding in Co(II) Mb, suggests utility of Co(II) Mb as Mb
      based oxygen carriers. The present results on cobalt-substituted Mb are useful in
      designing myoglobin-based oxygen carriers. 

PMID- 24866934
TI  - Enlarging the pi system of phosphorescent (C^C*) cyclometalated platinum(II) NHC
      complexes.
AB  - Cyclometalated (C^C*) platinum(II) N-heterocyclic carbene (NHC) complexes are
      emerging as a new class of phosphorescent emitters for the application in organic
      light-emitting devices (OLEDs). We present the synthesis of six new complexes of
      this class to investigate the influence of extended pi systems. Therefore, six
      different NHC ligands with a varying number of additional phenyl substituents
      were used in combination with the monoanionic acetylacetonate (acac) ligand to
      obtain complexes of the general formula [(NHC)Pt(II)(acac)]. The complexes were
      fully characterized by standard techniques and advanced spectroscopic methods
      ((195)Pt NMR). For all complexes the solid-state structure determination revealed
      a square-planar coordination of the platinum atom. Absorption and emission
      spectra were measured in thin amorphous poly(methyl methacrylate) films at room
      temperature. Four compounds emit in the blue-green region of the visible spectrum
      with quantum yields of up to 81%. 

PMID- 24866935
TI  - Multiscale structural gradients enhance the biomechanical functionality of the
      spider fang.
AB  - The spider fang is a natural injection needle, hierarchically built from a
      complex composite material comprising multiscale architectural gradients.
      Considering its biomechanical function, the spider fang has to sustain
      significant mechanical loads. Here we apply experiment-based structural modelling
      of the fang, followed by analytical mechanical description and Finite-Element
      simulations, the results of which indicate that the naturally evolved fang
      architecture results in highly adapted effective structural stiffness and damage
      resilience. The analysis methods and physical insights of this work are
      potentially important for investigating and understanding the architecture and
      structural motifs of sharp-edge biological elements such as stingers, teeth,
      claws and more. 

PMID- 24866939
TI  - Multifunctional nanostructures based on porous silica covered Fe3O4@CeO2-Pt
      composites: a thermally stable and magnetically-recyclable catalyst system.
AB  - A facile surface protected silica shell etching method for fabricating
      multifunctional Fe3O4@CeO2-Pt@mSiO2 composites is reported. These multifunctional
      materials possess large magnetization, open mesopores, and a stably confined but
      exposed catalytically active component. The unique structures showed high thermal
      stability, magnetic recyclability and catalytic activity in catalytic reactions. 

PMID- 24866938
TI  - Elastin-like polypeptides: the influence of its molecular weight on local
      hyperthermia-induced tumor accumulation.
AB  - Elastin-like polypeptides (ELP) are thermally responsive polypeptides that are
      soluble in solutions at 37 degrees C, but which aggregate above 42 degrees C. ELP
      can be used as effective carrier systems of anticancer molecules, because they
      can be targeted to tumor sites through the application of local hyperthermia.
      Since molecular size largely influences how successfully therapeutic agents can
      cross the vasculatures of tumors, it was crucial to determine an optimal
      molecular size. In this study, we designed and evaluated three ELP macromolecules
      with varying molecular weights (43, 63, and 122 kDa), with the goal of
      determining which would optimize the ELP drug delivery system. The N-terminus of
      the ELP macromolecule was modified with the cell penetrating peptide Bac to
      enhance intratumoral and intracellular uptake, and it was also confirmed that
      each polypeptide had the target transition temperature of 37-42 degrees C and the
      results of the studies, using tumor-bearing mice, showed that the tumor
      accumulations increased in the case of all three peptides when local hyperthermia
      was applied, but that the elimination patterns from these tumors varied according
      to peptide size. Local hyperthermia was found to produce prolonged retention of
      all ELP conjugates in tumors except Bac-ELP43. In addition, the pharmacokinetic
      analysis showed that two larger polypeptides with 63 and 122 kDa have increased
      AUC in comparison with the 43 kDa polypeptide. These results suggest that, when
      combined with local hyperthermia, the larger ELP conjugates (63 and 122 kDa) have
      advantages over the smaller Bac-ELP43 polypeptide in terms of enhanced
      permeability and higher retention effects.

PMID- 24866937
TI  - Comparison of the reactivity of carbohydrate photoaffinity probes with different
      photoreactive groups.
AB  - A judicious choice of photoreactive group is critical in successful photoaffinity
      labeling studies of small molecule-protein interactions. A set of carbohydrate
      based photoaffinity probes was prepared to compare the effects of three major
      photoreactive groups on the efficiency and selectivity of crosslinking a binding
      protein with low affinity. We showed that, despite the low crosslinking yield,
      the diazirine probe displayed the high ligand-dependent reactivity consistent
      with the ideal mechanism of photoaffinity labeling. Moreover, we demonstrated
      that, among the three photoreactive groups, only the diazirine probe achieved
      highly selective crosslinking of a low-affinity binding protein in cell lysate. 

PMID- 24866940
TI  - Successful removal of a huge hypervascular tentorial cavernous angioma after
      preoperative endovascular embolization.
AB  - The authors report a rare case of a huge hypervascular tentorial cavernous
      angioma treated with preoperative endovascular embolization, followed by
      successful gross-total removal. A 15-year-old girl presented with scintillation,
      diplopia, and papilledema. Computed tomography and MRI studies revealed a huge
      irregularly shaped tumor located in the right occipital and suboccipital regions.
      The tumor, which had both intra- and extradural components, showed marked
      enhancement and invasion of the overlying occipital bone. Angiography revealed
      marked tumor stain, with blood supply mainly from a large branch of the left
      posterior meningeal artery. Therefore, this lesion was diagnosed as a tentorium
      based extraaxial tumor. For differential diagnosis, meningioma,
      hemangiopericytoma, and malignant skull tumor were considered. Tumor feeders were
      endovascularly embolized with particles of polyvinyl alcohol. On the following
      day, the tumor was safely gross totally removed with minimum blood loss.
      Histopathological examination confirmed the diagnosis of cavernous angioma. To
      date, there have been no reports of tentorium-based cavernous angiomas
      endovascularly embolized preoperatively. A tentorial cavernous angioma is most
      likely to show massive intraoperative bleeding. Therefore, preoperative
      embolization appears to be quite useful for safe maximum resection. Hence, the
      authors assert that the differential diagnosis of tentorium-based tumors should
      include tentorial cavernous angioma, for which preoperative endovascular
      embolization should be considered. 

PMID- 24866942
TI  - Perovskite solar cells with 12.8% efficiency by using conjugated quinolizino
      acridine based hole transporting material.
AB  - A low band gap quinolizino acridine based molecule was designed and synthesized
      as new hole transporting material for organic-inorganic hybrid lead halide
      perovskite solar cells. The functionalized quinolizino acridine compound showed
      an effective hole mobility in the same range of the state-of-the-art spiro-MeOTAD
      and an appropriate oxidation potential of 5.23 eV vs the vacuum level. The device
      based on this new hole transporting material achieved high power conversion
      efficiency of 12.8% under the illumination of 98.8 mW cm(-2), which was better
      than the well-known spiro-MeOTAD under the same conditions. Moreover, this
      molecule could work alone without any additives, thus making it to be a promising
      candidate for solid-state photovoltaic application. 

PMID- 24866941
TI  - Admixture and the organization of genetic diversity in a butterfly species
      complex revealed through common and rare genetic variants.
AB  - Detailed information about the geographic distribution of genetic and genomic
      variation is necessary to better understand the organization and structure of
      biological diversity. In particular, spatial isolation within species and
      hybridization between them can blur species boundaries and create evolutionary
      relationships that are inconsistent with a strictly bifurcating tree model. Here,
      we analyse genome-wide DNA sequence and genetic ancestry variation in Lycaeides
      butterflies to quantify the effects of admixture and spatial isolation on how
      biological diversity is organized in this group. We document geographically
      widespread and pervasive historical admixture, with more restricted recent
      hybridization. This includes evidence supporting previously known and unknown
      instances of admixture. The genome composition of admixed individuals varies much
      more among than within populations, and tree- and genetic ancestry-based analyses
      indicate that multiple distinct admixed lineages or populations exist. We find
      that most genetic variants in Lycaeides are rare (minor allele frequency <0.5%).
      Because the spatial and taxonomic distributions of alleles reflect demographic
      and selective processes since mutation, rare alleles, which are presumably
      younger than common alleles, were spatially and taxonomically restricted compared
      with common variants. Thus, we show patterns of genetic variation in this group
      are multifaceted, and we argue that this complexity challenges simplistic notions
      concerning the organization of biological diversity into discrete, easily
      delineated and hierarchically structured entities.

PMID- 24866943
TI  - Current studies on sucrose isomerase and biological isomaltulose production using
      sucrose isomerase.
AB  - Isomaltulose is a natural isomer of sucrose. It is widely used as a functional
      sweetener with promising properties, including slower digestion, lower glycemic
      index, prolonged energy release, lower insulin reaction, and less cariogenicity.
      It has been approved as a safe sucrose substitute by the Food and Drug
      Administration of the US; Ministry of Health, Labor and Welfare of Japan; and the
      Commission of the European Communities. This article presents a review of recent
      studies on the properties, physiological effects, and food application of
      isomaltulose. In addition, the biochemical properties of sucrose isomerases
      producing isomaltulose are compared; the heterologous expression, fermentation
      optimization, structural determination, and catalysis mechanism of sucrose
      isomerase are reviewed; and the biotechnological production of isomaltulose from
      sucrose is summarized. 

PMID- 24866945
TI  - Biocompatibility evaluation of densified bacterial nanocellulose hydrogel as an
      implant material for auricular cartilage regeneration.
AB  - Bacterial nanocellulose (BNC), synthesized by the bacterium Gluconacetobacter
      xylinus, is composed of highly hydrated fibrils (99 % water) with high mechanical
      strength. These exceptional material properties make BNC a novel biomaterial for
      many potential medical and tissue engineering applications. Recently, BNC with
      cellulose content of 15 % has been proposed as an implant material for auricular
      cartilage replacement, since it matches the mechanical requirements of human
      auricular cartilage. This study investigates the biocompatibility of BNC with
      increased cellulose content (17 %) to evaluate its response in vitro and in vivo.
      Cylindrical BNC structures (O48 * 20 mm) were produced, purified in a built-in
      house perfusion system, and compressed to increase the cellulose content in BNC
      hydrogels. The reduction of endotoxicity of the material was quantified by
      bacterial endotoxin analysis throughout the purification process. Afterward, the
      biocompatibility of the purified BNC hydrogels with cellulose content of 17 % was
      assessed in vitro and in vivo, according to standards set forth in ISO 10993. The
      endotoxin content in non-purified BNC (2,390 endotoxin units (EU)/ml) was reduced
      to 0.10 EU/ml after the purification process, level well below the endotoxin
      threshold set for medical devices. Furthermore, the biocompatibility tests
      demonstrated that densified BNC hydrogels are non-cytotoxic and cause a minimal
      foreign body response. In support with our previous findings, this study
      concludes that BNC with increased cellulose content of 17 % is a promising non
      resorbable biomaterial for auricular cartilage tissue engineering, due to its
      similarity with auricular cartilage in terms of mechanical strength and host
      tissue response.

PMID- 24866948
TI  - [Clinical science needs smart minds].

PMID- 24866946
TI  - Corynebacterium glutamicum sdhA encoding succinate dehydrogenase subunit A plays
      a role in cysR-mediated sulfur metabolism.
AB  - The Corynebacterium glutamicum CysR protein plays a critical regulatory role in
      sulfur metabolism. In this study, we isolated a protein interacting with CysR by
      employing a two-hybrid system. Subsequent analysis identified the gene as sdhA
      annotated to encode succinate dehydrogenase flavoprotein subunit A, a Krebs cycle
      enzyme. Deletion of the gene (DeltasdhA) severely affected cell growth and final
      cell yield, particularly in complex media. In addition, the DeltasdhA mutant
      strain was unable to use acetate as the sole carbon source, showing the identity
      of the gene. Transcription of the cysR gene and genes known to be regulated by
      cysR was affected in the DeltasdhA mutant strain, suggesting a positive role for
      sdhA on cysR. Furthermore, DeltasdhA cells showed increased sensitivity to
      oxidants, such as diamide, menadione, and hydrogen peroxide. In DeltasdhA cells,
      the trx gene, which encodes thioredoxin reductase, was severely repressed. Taken
      together, our findings show that the SdhA protein not only performs a role as a
      TCA enzyme but also communicates with sulfur metabolism, thereby regulating genes
      involved in redox homeostasis.

PMID- 24866947
TI  - Cometabolic degradation of organic wastewater micropollutants by activated sludge
      and sludge-inherent microorganisms.
AB  - Municipal wastewaters contain a multitude of organic trace pollutants. Often,
      their biodegradability by activated sludge microorganisms is decisive for their
      elimination during wastewater treatment. Since the amounts of micropollutants
      seem too low to serve as growth substrate, cometabolism is supposed to be the
      dominating biodegradation process. Nevertheless, as many biodegradation studies
      were performed without the intention to discriminate between metabolic and
      cometabolic processes, the specific contribution of the latter to substance
      transformations is often not clarified. This minireview summarizes current
      knowledge about the cometabolic degradation of organic trace pollutants by
      activated sludge and sludge-inherent microorganisms. Due to their relevance for
      communal wastewater contamination, the focus is laid on pharmaceuticals, personal
      care products, antibiotics, estrogens, and nonylphenols. Wherever possible,
      reference is made to the molecular process level, i.e., cometabolic pathways,
      involved enzymes, and formed transformation products. Particular cometabolic
      capabilities of different activated sludge consortia and various microbial
      species are highlighted. Process conditions favoring cometabolic activities are
      emphasized. Finally, knowledge gaps are identified, and research perspectives are
      outlined.

PMID- 24866949
TI  - [Contrast-enhanced ultrasound in vascular medicine: what is new?].

PMID- 24866950
TI  - [Lipoprotein(a): a risk factor for atherosclerosis].

PMID- 24866944
TI  - Indigenous oil-degrading bacteria in crude oil-contaminated seawater of the
      Yellow sea, China.
AB  - Indigenous oil-degrading bacteria play an important role in efficient remediation
      of polluted marine environments. In this study, we investigated the diversity and
      abundance of indigenous oil-degrading bacteria and functional genes in crude oil
      contaminated seawater of the Dalian coast. The gene copy number bacterial 16S
      rRNA in total were determined to be about 10(10) copies L(-1) in contaminated
      seawater and 10(9) copies L(-1) in uncontaminated seawater. Bacteria of
      Alcanivorax, Marinobacter, Novosphingobium, Rhodococcus, and Pseudoalteromonas
      were found to be predominant oil-degrading bacteria in the polluted seawater in
      situ. In addition, bacteria belonging to Algoriphagus, Aestuariibacter,
      Celeribacter, Fabibacter, Zobellia, Tenacibaculum, Citreicella, Roseivirga,
      Winogradskyella, Thioclava, Polaribacter, and Pelagibaca were confirmed to be the
      first time as an oil-degrading bacterium. The indigenous functional enzymes,
      including AlkB or polycyclic aromatic hydrocarbons ring-hydroxylating
      dioxygenases alpha (PAH-RHDalpha) coding genes from Gram-positive (GP) and Gram
      negative bacteria (GN), were revealed and quite diverse. About 10(10) to 10(11)
      copies L(-1) for the expression of alkB genes were recovered and showed that the
      two-thirds of all the AlkB sequences were closely related to widely distributed
      Alcanivorax and Marinobacter isolates. About 10(9) copies L(-1) seawater for the
      expression of RHDalphaGN genes in contaminated seawater and showed that almost
      all RHDalphaGN sequences were closely related to an uncultured bacterium;
      however, RHDalphaGP genes represented only about 10(5) copies L(-1) seawater for
      the expression of genes in contaminated seawater, and the naphthalene dioxygenase
      sequences from Rhodococcus and Mycobacterium species were most abundant.
      Together, their data provide evidence that there exists an active aerobic
      microbial community indigenous to the coastal area of the Yellow sea that is
      capable of degrading petroleum hydrocarbons. 

PMID- 24866951
TI  - [Geriatric traumatology: interdisciplinary management of patients with fragility
      fractures].

PMID- 24866952
TI  - [Treatment of peripheral T-cell lymphoma].

PMID- 24866953
TI  - [HIV infection: high standard of treatment, new goals].

PMID- 24866954
TI  - [Carotid atherosclerosis in coronary heart disease].

PMID- 24866955
TI  - [Dialysis and renal transplantation: update 2014].

PMID- 24866956
TI  - [Sleep medicine: new data].

PMID- 24866957
TI  - [Vasculitis: update 2014].

PMID- 24866958
TI  - [Fecal microbiota transplantation: when and for whom?].

PMID- 24866960
TI  - [24-year old patient with increase in neck size and change in his voice after
      coughing].

PMID- 24866961
TI  - [Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) in a 67
      year-old patient with chronic coughing].
AB  - HISTORY AND CLINICAL FINDINGS: A 67-year-old woman with a history of chronic
      obstructive pulmonary disease and breast cancer developed an increase in size and
      number of pulmonary nodules that had previously been stable over the course of 9
      years. INVESTIGATIONS: Thoracic computed tomography revealed a well-defined
      pulmonary lesion with a diameter of 1,1 * 1,1 cm, accompanied by multiple
      bilateral pulmonary nodules with a maximum size of 5 mm. Thoracoscopic resection
      of the major nodule was extended to a completive resection of an adjacent lung
      area that operatively showed a macroscopically noticeable hypervascularity.
      Histopathological examination assigned the larger lesion to a typical carcinoid;
      the additionally resected hypervascular lung parenchyma confirmed an accumulation
      of hyperplastic neuroendocrine cells in terms of a diffuse idiopathic pulmonary
      neuroendocrine cell hyperplasia (DIPNECH). TREATMENT AND COURSE: Since
      histological examination showed an entirely resected neuroendocrine tumor
      classified as typical carcinoid, and considering DIPNECH to be a preinvasive
      lesion, the therapeutic management consisted of serial imaging by computed
      tomography. During the last two years, no progression of either the pulmonary
      lesions or of the obstructive disease was observed. CONCLUSION: DIPNECH is a
      rare, primary pulmonary process with proliferation of hyperplastic neuroendocrine
      cells, affecting principally middle-aged, non-smoking women. It is considered to
      be a precursor lesion to pulmonary carcinoid tumors. Given its only minor risk of
      invasive metastatic spread, serial imaging for timely detection of progressing
      lesions and optimizing of concomitant obstructive pulmonary disease are the
      preferred treatment approaches.

PMID- 24866962
TI  - [Mental healthcare in Germany--current situation and perspectives].
AB  - For several years, there has been a significant increase of the utilization of
      health care due to mental disorders in Germany. Epidemiologic studies dealing
      with the prevalence of mental disorders show that the prevalence of mental
      disorders haven't increased. In consideration of the relative stable prevalence,
      currently there are only speculations about the reasons for the increasing
      service utilization. The capacity of psychiatric-psychosomatic-psychotherapeutic
      health care services is increasing. Despite the fact that capacity is increasing,
      in the outpatient and inpatient sector it comes apparent that there is an
      increasing burden, indicating that the demand for mental health care is not met
      by the capacity of psychiatric-psychosomatic-psychotherapeutic health care
      services. Health care provision by general practitioners and somatic disciplines
      predominate, going along with low cross-disciplinary and coordinated cooperation.
      So far, cooperative, intersectoral care models for mental disorders have been
      realized only in individual projects. Valid data are lacking, which need to
      reveal the causes and especially the consequences of this situation of mental
      health care provision and provide reference standards for an optimized, need
      based care planning. For this reason, it is imperative to advance quality
      management for the care of mental disorders. With a view to the high rates of
      somatic comorbidity, an expansion of cooperative forms of mental health care
      appears essential.

PMID- 24866963
TI  - The binding site for the transcription factor, NF-kappaB, on the cystathionine
      gamma-lyase promoter is critical for LPS-induced cystathionine gamma-lyase
      expression.
AB  - Hydrogen sulfide (H2S) is regarded as the third endogenous gaseous signaling
      molecule. Cystathioine gamma-lyase (CSE), one of the three enzymes in the
      transsulfuration pathway, is responsible for the production of endogenous H2S.
      The H2S/CSE signaling pathway is involved in the inflammation induced by
      lipopolysaccharides (LPS). Therefore, in this study, we investigated the effects
      of the binding site (on the CSE promoter) for the transcription factor, nuclear
      factor (NF)-kappaB, on the transcriptional regulation of the CSE gene in
      mammalian cells treated with LPS. For this purpose, HEK-293 and COS-7 cells were
      transfected with 5 ug pGL4.12-KM1478 or 5 ug pGL4.12-KM1478m (mutant) together
      with the pRL-CMV control vector (0.032 ug for the HEK-293 cells, 0.0032 ug for
      the COS-7 cells). Subsequently, the cells were treated with LPS for 6 h. The
      expression of CSE was measured by RT-qPCR. cDNA pooled from J774.1A and RAW264.7
      cells treated with LPS for 6 h was used to estimate the quantity of the
      transcripts. Our results revealed that LPS markedly increased the mRNA and
      protein expression levels of the CSE gene in the J774.1A and RAW264.7 cells
      following treatment with LPS for 6 h. In addition, we found that the GGGACATTCC
      DNA sequence on the promoter of the CSE gene was closely associated with the
      transcriptional regulation of the CSE gene in the HEK-293 and COS-7 cells treated
      with LPS. Taken together, our data suggest that the NF-kappaB binding site on CSE
      promoter is critical for LPS-induced CSE expression in mammalian cells.

PMID- 24866964
TI  - Organ donation and transplantation in europe: the highlights.

PMID- 24866966
TI  - Recent progress in biointerfaces with controlled bacterial adhesion by using
      chemical and physical methods.
AB  - Biointerfaces with the controlled adhesion of bacteria are highly important,
      owing to their wide applications, which range from decreasing the probability of
      infection to promoting higher efficiency and sensitivity in biocatalysts and
      biosensors. In this Focus Review, we summarize the recent progress in chemically
      and physically designed biointerfaces with controlled bacterial adhesion. On one
      hand, several smart-responsive biointerfaces that can be switched between
      bacteria-adhesive states and bacteria-resistant states by applying an external
      stimulus have been rationally designed and developed for adhering and detaching
      bacteria, whilst, on the other hand, the adhesive behavior of bacteria can be
      controlled by regulating the topography of the biointerface. In addition, new
      technologies (i.e., biosensors) and materials (i.e., graphene) provide promising
      approaches for efficiently controlling the adhesion of bacteria for practical
      applications. 

PMID- 24866968
TI  - To what extent is alliance affected by transference? An empirical exploration.
AB  - Will patients project their representations of significant others onto the
      therapist in a way that influences the formation of the therapeutic alliance? To
      address this issue, the current study explored the following questions: (1) To
      what extent are pretreatment representations of others projected onto the
      therapist and thereby predict the development of alliance throughout the course
      of treatment? (2) To what extent are these projections affected by the real
      relationship? (3) Are there specific representations of others that are more
      prone to be projected onto the alliance? To this end, data on 134 patients from a
      randomized controlled trial for depression comparing dynamic supportive
      expressive therapy with supportive clinical management combined with
      pharmacotherapy or placebo were used. Findings demonstrated that the patients'
      pretreatment representations of significant others predicted a substantial part
      of the alliance with the therapist throughout the course of treatment. However,
      the representations of others were not automatically projected onto the alliance
      but rather the projections were also influenced by the real relationship with the
      therapist. Throughout this process, the alliance evolves into a collage of
      significant others. A process of assimilation seemed to emerge during treatment,
      in which the most relevant representations of significant others were projected
      onto the alliance with the therapist.

PMID- 24866967
TI  - Predicting early positive change in multisystemic therapy with youth exhibiting
      antisocial behaviors.
AB  - This study examined individual and family characteristics that predicted early
      positive change in the context of Multisystemic Therapy (MST). Families (n = 185;
      65% male; average youth age 15 years) receiving MST in community settings
      completed assessments at the outset of treatment and 6-12 weeks into treatment.
      Early positive changes in youth antisocial behavior were assessed using the
      caregiver report on the Child Behavior Checklist Externalizing Behaviors subscale
      and youth report on the Self-Report Delinquency Scale. Overall, families showed
      significant positive changes by 6-12 weeks into treatment; these early changes
      were maintained into midtreatment 6-12 weeks later. Families who exhibited
      clinically significant gains early in treatment were more likely to terminate
      treatment successfully compared with those who did not show these gains. Low
      youth internalizing behaviors and absence of youth drug use predicted early
      positive changes in MST. High levels of parental monitoring and low levels of
      affiliation with deviant peers (mechanisms known to be associated with MST
      success) were also associated with early positive change.

PMID- 24866969
TI  - Alliance ruptures, impasses, and enactments: a relational perspective.
AB  - Alliance ruptures, impasses, and transference-countertransference enactments are
      inevitable in therapy. A growing body of evidence suggests that repairing
      ruptures in the alliance is related to positive outcome (Safran, Muran, & Eubanks
      Carter, 2011). Our research program has led to the development of training
      methods to enhance therapists' abilities to detect and work constructively with
      alliance ruptures and negative therapeutic process (Safran et al., 2014). This
      article outlines relevant theoretical underpinnings, intervention principles, and
      empirical findings.

PMID- 24866970
TI  - Perfectionism affects change in psychological symptoms.
AB  - The primary goal of this study was to examine how perfectionism affects
      psychological symptoms during the course of treatment. We examined session-by
      session symptom changes in a sample of 105 adult clients who presented for
      counseling at a psychology training clinic housed at a large Midwestern
      university in the United States. Using a recently developed measure of
      perfectionism (Short Almost Perfect Scale [SAPS]) that possesses good
      psychometric features, we were able to investigate effects of both maladaptive
      (high self-criticism) and adaptive (high standards with low self-criticism)
      perfectionistic characteristics on indicators of personal and interpersonal
      psychological distress across time. Multilevel modeling analyses indicated that
      both symptomatic distress and interpersonal problems improved over the course of
      therapy. Maladaptive perfectionism was associated with higher levels of
      interpersonal problems and distress at the outset of therapy, and related
      differentially to change patterns in symptom distress and interpersonal problems
      over the course of treatment. Maladaptive perfectionism, however, was not related
      to level of symptoms at the end of therapy. Adaptive perfectionistic
      characteristics were associated with fewer interpersonal problems at the
      beginning and end of therapy. Results suggest the value of assessing
      perfectionistic characteristics at the onset of treatment, even for clients not
      presenting with obvious concerns linked to such individual differences.

PMID- 24866971
TI  - The stigma of having psychological problems: relations with engagement, working
      alliance, and depression in psychotherapy.
AB  - The stigma of having psychological problems is a barrier to seeking mental health
      treatment, but little research has examined whether this stigma influences the
      experiences of those in treatment. In a sample of 42 psychotherapy clients, we
      explored links over the first few sessions between 2 facets of stigma (self
      stigma and perceived public stigma) and 3 variables germane to the therapeutic
      process (depression, working alliance, and engagement). Initial self-stigma (SS)
      level was positively associated with initial depression, negatively associated
      with initial working alliance, and unrelated to initial engagement. Initial
      perceived public stigma (PPS) level was unrelated to initial levels in the 3
      outcome variables. Initial SS and PPS levels were both generally unrelated to
      linear changes in the outcomes over the initial phase of counseling. Relations
      between stigma and outcome variables often differed within- and between-persons.
      For example, the association between PPS and engagement was negative at the
      between-person level but positive at the within-person level. Finally, on
      average, PPS decreased over the first few sessions but SS remained constant. Such
      findings may help therapists better understand the role of stigma in their
      clinical work, and stimulate research examining how to address stigmatization in
      psychotherapy.

PMID- 24866972
TI  - Computational psychotherapy research: scaling up the evaluation of patient
      provider interactions.
AB  - In psychotherapy, the patient-provider interaction contains the treatment's
      active ingredients. However, the technology for analyzing the content of this
      interaction has not fundamentally changed in decades, limiting both the scale and
      specificity of psychotherapy research. New methods are required to "scale up" to
      larger evaluation tasks and "drill down" into the raw linguistic data of patient
      therapist interactions. In the current article, we demonstrate the utility of
      statistical text analysis models called topic models for discovering the
      underlying linguistic structure in psychotherapy. Topic models identify semantic
      themes (or topics) in a collection of documents (here, transcripts). We used
      topic models to summarize and visualize 1,553 psychotherapy and drug therapy
      (i.e., medication management) transcripts. Results showed that topic models
      identified clinically relevant content, including affective, relational, and
      intervention related topics. In addition, topic models learned to identify
      specific types of therapist statements associated with treatment-related codes
      (e.g., different treatment approaches, patient-therapist discussions about the
      therapeutic relationship). Visualizations of semantic similarity across sessions
      indicate that topic models identify content that discriminates between broad
      classes of therapy (e.g., cognitive-behavioral therapy vs. psychodynamic
      therapy). Finally, predictive modeling demonstrated that topic model-derived
      features can classify therapy type with a high degree of accuracy. Computational
      psychotherapy research has the potential to scale up the study of psychotherapy
      to thousands of sessions at a time. We conclude by discussing the implications of
      computational methods such as topic models for the future of psychotherapy
      research and practice.

PMID- 24866975
TI  - Sonographic criteria predictive of benign thyroid nodules useful in avoiding
      unnecessary ultrasound-guided fine needle aspiration.
AB  - BACKGROUND/PURPOSE: There has been no individual ultrasound feature of having
      high accuracy for diagnosis of thyroid malignancy. In this study, we aimed to
      establish feature-oriented criteria to characterize benign thyroid nodules that
      do not require ultrasound (US)-guided fine needle aspiration (FNA). METHODS: We
      reviewed 374 patients with thyroid nodules who had undergone US-guided FNA at our
      institution (2005-2008). Thyroid nodules were classified into two groups:
      Category 1 (benign nodules that required follow-up 6-12 months later but not US
      guided FNA); and Category 2 (indeterminate nodules or suspected carcinoma that
      required US-guided FNA). To test the validity, we reviewed 315 consecutive
      patients who had histologically proven thyroid carcinoma (n = 39) and randomly
      selected 40 of the 276 patients with benign nodules (2009-2010). RESULTS: Of 374
      nodules, 354 (95%) were benign and 20 (5%) malignant. On US, 260 nodules had no
      calcification, no increase in vascularity, well-defined margin, and no
      lymphadenopathy (Category 1). Using a combination of these four features, we were
      able to discriminate benign from indeterminate nodules or suspected malignant
      nodules with a sensitivity of 73%, and specificity and positive predictive value
      of 100%. Validity testing revealed that none of the 39 malignant thyroid nodules
      had all four US features. All Category 1 nodules (2005-2008) remained benign at
      the 3-years follow up. CONCLUSION: The combination of four US features of
      Category 1 nodules is highly predictive of benign disease, and we could avoid
      unnecessary US-guided FNA in 69.5% of our patients using this combined features.

PMID- 24866976
TI  - Megakaryocytic irreversible P-TEFb activation.

PMID- 24866977
TI  - Domain-specific control of selective attention.
AB  - Previous research has shown that loading information on working memory affects
      selective attention. However, whether the load effect on selective attention is
      domain-general or domain-specific remains unresolved. The domain-general effect
      refers to the findings that load in one content (e.g. phonological) domain in
      working memory influences processing in another content (e.g., visuospatial)
      domain. Attentional control supervises selection regardless of information
      domain. The domain-specific effect refers to the constraint of influence only
      when maintenance and processing operate in the same domain. Selective attention
      operates in a specific content domain. This study is designed to resolve this
      controversy. Across three experiments, we manipulated the type of representation
      maintained in working memory and the type of representation upon which the
      participants must exert control to resolve conflict and select a target into the
      focus of attention. In Experiments 1a and 1b, participants maintained digits and
      nonverbalized objects, respectively, in working memory while selecting a target
      in a letter array. In Experiment 2, we presented auditory digits with a letter
      flanker task to exclude the involvement of resource competition within the same
      input modality. In Experiments 3a and 3b, we replaced the letter flanker task
      with an object flanker task while manipulating the memory load on object and
      digit representation, respectively. The results consistently showed that memory
      load modulated distractibility only when the stimuli of the two tasks were
      represented in the same domain. The magnitude of distractor interference was
      larger under high load than under low load, reflecting a lower efficacy of
      information prioritization. When the stimuli of the two tasks were represented in
      different domains, memory load did not modulate distractibility. Control of
      processing priority in selective attention demands domain-specific resources. 

PMID- 24866973
TI  - Biosynthesis and roles of phospholipids in mitochondrial fusion, division and
      mitophagy.
AB  - Mitochondria move, fuse and divide in cells. The dynamic behavior of mitochondria
      is central to the control of their structure and function. Three conserved
      mitochondrial dynamin-related GTPases (i.e., mitofusin, Opa1 and Drp1 in mammals
      and Fzo1, Mgm1 and Dnm1 in yeast) mediate mitochondrial fusion and division. In
      addition to dynamins, recent studies demonstrated that phospholipids in
      mitochondria also play key roles in mitochondrial dynamics by interacting with
      dynamin GTPases and by directly changing the biophysical properties of the
      mitochondrial membranes. Changes in phospholipid composition also promote
      mitophagy, which is a selective mitochondrial degradation process that is
      mechanistically coupled to mitochondrial division. In this review, we will
      discuss the biogenesis and function of mitochondrial phospholipids. 

PMID- 24866978
TI  - A geometric model of plaque incision and graft for Peyronie's disease with
      geometric analyses of different techniques.
AB  - INTRODUCTION: A surgical approach with plaque incision and graft (PIG) to correct
      Peyronie's disease is the best method for complex, large deviations. However, the
      geometric and mechanical consequences of this intervention are poorly understood.
      AIM: The aim of this study was to analyze the geometric and mechanical
      consequences of PIG on penile straighten surgery. METHOD: A tridimensional penile
      simile model with a curvature of 85 degrees  was created to test all of the most
      common PIG techniques. PIG with double-Y, H-shape, and Egydio techniques were
      used to rectify the curved penile model. MAIN OUTCOME MEASUREMENTS: The results
      that differed from a rectified cylinder shape were highlighted. RESULTS: All of
      the analyzed techniques created a geometric distortion that could be linked to
      poor surgical results. We suggest a new technique to resolve these abnormalities.
      CONCLUSION: Current techniques designed to correct penile deviation using PIG
      present geometric and mechanical imperfections with potential consequences to the
      postoperative success rate. The new technique proposed in this report could be a
      possible solution to solve the geometric distortion caused by PIG.

PMID- 24866979
TI  - Is generalized reaction after exposure to big cats at the circus really
      unpredictable in highly cat-allergic individuals?

PMID- 24866984
TI  - Trophic disruption: a meta-analysis of how habitat fragmentation affects resource
      consumption in terrestrial arthropod systems.
AB  - Habitat fragmentation is a complex process that affects ecological systems in
      diverse ways, altering everything from population persistence to ecosystem
      function. Despite widespread recognition that habitat fragmentation can influence
      food web interactions, consensus on the factors underlying variation in the
      impacts of fragmentation across systems remains elusive. In this study, we
      conduct a systematic review and meta-analysis to quantify the effects of habitat
      fragmentation and spatial habitat structure on resource consumption in
      terrestrial arthropod food webs. Across 419 studies, we found a negative overall
      effect of fragmentation on resource consumption. Variation in effect size was
      extensive but predictable. Specifically, resource consumption was reduced on
      small, isolated habitat fragments, higher at patch edges, and neutral with
      respect to landscape-scale spatial variables. In general, resource consumption
      increased in fragmented settings for habitat generalist consumers but decreased
      for specialist consumers. Our study demonstrates widespread disruption of trophic
      interactions in fragmented habitats and describes variation among studies that is
      largely predictable based on the ecological traits of the interacting species. We
      highlight future prospects for understanding how changes in spatial habitat
      structure may influence trophic modules and food webs. 

PMID- 24866986
TI  - Statins in the elderly: an answered question?
AB  - PURPOSE OF REVIEW: A strong potential exists for greater promotion of statin
      therapy among the over-70 age group on the basis of their high absolute
      cardiovascular risk. However, the evidence for this approach is currently
      unclear. RECENT FINDINGS: Meta-analysis of trials highlights the uncertainty
      about the efficacy of statins in the prevention of major vascular events and all
      cause mortality in the elderly. This stems from inadequate numbers of
      participants from this age group included in previous randomized clinical trials.
      Adverse effects of statins are likely to be greater in the elderly, but their
      frequency is uncertain and their contribution to frailty and loss of independence
      in the elderly has been little studied. SUMMARY: Real world trials examining the
      impact of statin therapy in the elderly are now called for.

PMID- 24866985
TI  - College students' knowledge about fetal alcohol spectrum disorder.
AB  - BACKGROUND: Fetal Alcohol Spectrum Disorders (FASDs) are the leading known
      preventable birth defects in North America. Knowledge surveys about FASD have
      been conducted with various health and allied healthcare providers and have
      proven useful in identifying gaps in knowledge and differences among provider
      groups to support prevention efforts. To date, no research has been conducted
      exploring FASD knowledge among college students. OBJECTIVE: This study explored
      FASD knowledge in a sample of college students, a group at particularly high risk
      for alcohol-exposed pregnancies. Findings are compared to professionals in
      several healthcare and affiliated professional groups who were previously
      surveyed with the same FASD-related items. METHODS: Surveys from 1,035 college
      students at a northwestern university were analyzed. Included with the ACHA
      National College Health Assessment II were questions regarding FASD. College
      students' knowledge was compared with that of professionals in key healthcare and
      affiliated positions to define their relative awareness of FASD risk. RESULTS:
      Overall, findings revealed adequate FASD knowledge among college students.
      Although minor differences emerged when comparing students and professionals'
      responses, most respondent groups answered with an 85% accuracy rate or higher.
      CONCLUSION: College students demonstrated adequate knowledgeable about FASD.
      Future research must explore whether such knowledge translates into lower risk
      behavior and consequent reduction in alcohol-exposed pregnancies.

PMID- 24866987
TI  - Efficient thermolysis route to monodisperse Cu2ZnSnS4 nanocrystals with
      controlled shape and structure.
AB  - Monodisperse Cu2ZnSnS4 (CZTS) nanocrystals with tunable shape, crystalline phase,
      and composition are synthesized by efficient thermolysis of a single source
      precursor of mixed metal-oleate complexes in hot organic solvents with dissolved
      sulfur sources. Suitable tuning of the synthetic conditions and the Cu/(Zn + Sn)
      ratio of the precursor has enabled precise control of the crystalline phase in
      the form of kesterite, or a newly observed wurtzite structure. Nanocrystals with
      morphology in the form of spherical, rice-like, or rod-like shapes are obtained
      over a wide range of compositions (0.5 <= Cu/(Zn + Sn) <= 1.2). Both the final
      products and intermediates for each shape exhibit consistent composition and
      structure, indicating homogenous nucleation and growth of single-phase
      nanocrystals. Thin films prepared from colloidal nanocrystal suspensions display
      interesting shape-dependent photoresponse behavior under white light illumination
      from a solar simulator. 

PMID- 24866988
TI  - Vessel generator noise as a settlement cue for marine biofouling species.
AB  - Underwater noise is increasing globally, largely due to increased vessel numbers
      and international ocean trade. Vessels are also a major vector for translocation
      of non-indigenous marine species which can have serious implications for
      biosecurity. The possibility that underwater noise from fishing vessels may
      promote settlement of biofouling on hulls was investigated for the ascidian Ciona
      intestinalis. Spatial differences in biofouling appear to be correlated with
      spatial differences in the intensity and frequency of the noise emitted by the
      vessel's generator. This correlation was confirmed in laboratory experiments
      where C. intestinalis larvae showed significantly faster settlement and
      metamorphosis when exposed to the underwater noise produced by the vessel
      generator. Larval survival rates were also significantly higher in treatments
      exposed to vessel generator noise. Enhanced settlement attributable to vessel
      generator noise may indicate that vessels not only provide a suitable fouling
      substratum, but vessels running generators may be attracting larvae and enhancing
      their survival and growth. 

PMID- 24866994
TI  - The ball on shipboard: James Tissot.

PMID- 24866995
TI  - USPSTF: Low-dose aspirin may help reduce risk of preeclampsia.

PMID- 24866990
TI  - OMIP-022: Comprehensive assessment of antigen-specific human T-cell functionality
      and memory.

PMID- 24867009
TI  - Genomics-enabled drug repositioning and repurposing: insights from an IOM
      Roundtable activity.

PMID- 24866991
TI  - Effect of naltrexone on neuropathic pain in mice locally transfected with the
      mutant MU-opioid receptor gene in spinal cord.
AB  - BACKGROUND AND PURPOSE: Opioid antagonists, such as naloxone and naltrexone,
      exhibit agonistic properties at the mutated MU receptor, MOR-S196ACSTA. In our
      previous study, systemic naloxone (10 mg.kg(-1) , s.c.) elicited antinociceptive
      effect without the induction of tolerance, dependence or rewarding effect in mice
      2 weeks after intrathecal administration of double-stranded adeno-associated
      virus-MOR-S196ACSTA-eGFP. Here, we have investigated if this antinociceptive
      paradigm would be effective in a mouse model of neuropathic pain. EXPERIMENTAL
      APPROACH: Spinal nerves were ligated in male C57BL/6 mice 3 or 4 weeks after
      intrathecal injection of the lentivirus encoding the construct of MOR-S196ACSTA
      eGFP (LV-MOR-S196ACSTA). Anti-allodynic effects of daily s.c.injections of
      saline, naltrexone (10 mg.kg(-1) ) or morphine (10 mg.kg(-1) ) were assessed by
      the von Frey test. After 14 days of treatment with saline, naltrexone or
      morphine, signs of natural withdrawal were measured at 22 and 46 h after the last
      injection. To determine the rewarding effects induced by morphine or naltrexone,
      the conditioned place preference test was carried out. KEY RESULTS: Anti
      allodynic effects, as measured by von Frey test, increased after naltrexone or
      morphine treatment in mice transfected with LV-MOR-S196ACSTA in the spinal cord.
      Cessation of treatment with morphine, but not naltrexone, induced natural
      withdrawal and rewarding effects. CONCLUSIONS AND IMPLICATIONS: Systemic
      injection of naltrexone after the expression of a mutant MU opioid receptor, MOR
      S196ACSTA, in the spinal cord may have therapeutic potential for chronic
      neuropathic pain, without the development of dependence or addiction. LINKED
      ARTICLES: This article is part of a themed section on Opioids: New Pathways to
      Functional Selectivity. To view the other articles in this section visit
      http://dx.doi.org/10.1111/bph.2015.172.issue-2.

PMID- 24867010
TI  - A piece of my mind. Hounded.

PMID- 24867011
TI  - Updating practice guidelines.

PMID- 24867012
TI  - Durability of class I American College of Cardiology/American Heart Association
      clinical practice guideline recommendations.
AB  - IMPORTANCE: Little is known regarding the durability of clinical practice
      guideline recommendations over time. OBJECTIVE: To characterize variations in the
      durability of class I ("procedure/treatment should be performed/administered")
      American College of Cardiology/American Heart Association (ACC/AHA) guideline
      recommendations. DESIGN, SETTING, AND PARTICIPANTS: Textual analysis by 4
      independent reviewers of 11 guidelines published between 1998 and 2007 and
      revised between 2006 and 2013. MAIN OUTCOMES AND MEASURES: We abstracted all
      class I recommendations from the first of the 2 most recent versions of each
      guideline and identified corresponding recommendations in the subsequent version.
      We classified recommendations replaced by less determinate or contrary
      recommendations as having been downgraded or reversed; we classified
      recommendations for which no corresponding item could be identified as having
      been omitted. We tested for differences in the durability of recommendations
      according to guideline topic and underlying level of evidence using bivariable
      hypothesis tests and conditional logistic regression. RESULTS: Of 619 index
      recommendations, 495 (80.0%; 95% CI, 76.6%-83.1%) were retained in the subsequent
      guideline version, 57 (9.2%; 95% CI, 7.0%-11.8%) were downgraded or reversed, and
      67 (10.8%; 95% CI, 8.4%-13.3%) were omitted. The percentage of recommendations
      retained varied across guidelines from 15.4% (95% CI, 1.9%-45.4%) to 94.1% (95%
      CI, 80.3%-99.3%; P < .001). Among recommendations with available information on
      level of evidence, 90.5% (95% CI, 83.2%-95.3%) of recommendations supported by
      multiple randomized studies were retained, vs 81.0% (95% CI, 74.8%-86.3%) of
      recommendations supported by 1 randomized trial or observational data and 73.7%
      (95% CI, 65.8%-80.5%) of recommendations supported by opinion (P = .001). After
      accounting for guideline-level factors, the probability of being downgraded,
      reversed, or omitted was greater for recommendations based on opinion (odds
      ratio, 3.14; 95% CI, 1.69-5.85; P < .001) or on 1 trial or observational data
      (odds ratio, 3.49; 95% CI, 1.45-8.41; P = .005) vs recommendations based on
      multiple trials. CONCLUSIONS AND RELEVANCE: The durability of class I cardiology
      guideline recommendations for procedures and treatments promulgated by the
      ACC/AHA varied across individual guidelines and levels of evidence. Downgrades,
      reversals, and omissions were most common among recommendations not supported by
      multiple randomized studies.

PMID- 24867014
TI  - Preoperative assessment of the older patient: a narrative review.
AB  - IMPORTANCE: Surgery in older patients often poses risks of death, complications,
      and functional decline. Prior to surgery, evaluations of health-related
      priorities, realistic assessments of surgical risks, and individualized
      optimization strategies are essential. OBJECTIVE: To review surgical decision
      making for older adult patients by 2 measures: defining treatment goals for
      elderly patients and reviewing the evidence relating risk factors to adverse
      outcomes. Assessment and optimization strategies for older surgical patients are
      proposed. EVIDENCE ACQUISITION: A review of studies relating geriatric conditions
      such as functional and cognitive impairment, malnutrition, facility residence,
      and frailty to postoperative mortality and complications (including delirium,
      discharge to an institution, and functional decline). Medline, EMBASE, and Web of
      Science databases were searched for articles published between January 1, 2000,
      and December 31, 2013, that included patients older than 60 years. RESULTS: This
      review identified 54 studies of older patients; 28 that examined preoperative
      clinical features associated with mortality (n = 1,422,433 patients) and 26 that
      examined factors associated with surgical complications (n = 136,083 patients).
      There was substantial heterogeneity in study methods, measures, and outcomes. The
      absolute risk and risk ratios relating preoperative clinical conditions to
      mortality varied widely: 10% to 40% for cognitive impairment (adjusted hazard
      ratio [HR], 1.26 [95% CI, 1.06-1.49] to 5.77 [95% CI, 1.55-21.55]), 10% to 17%
      for malnutrition (adjusted odds ratio [OR], 0.88 [95% CI, 0.78-1.01] to 59.2 [95%
      CI, 3.6-982.9]), and 11% to 41% for institutionalization (adjusted OR, 1.5 [95%
      CI, 1.02-2.21] to 3.27 [95% CI, 2.81-3.81]).) Risk ratios for functional
      dependence relating to mortality ranged from an adjusted HR of 1.02 (95% CI, 0.99
      1.04) to an adjusted OR of 18.7 (95% CI, 1.6-215.3) and for frailty relating to
      mortality, ranged from an adjusted HR of 1.10 (95% CI, 1.04-1.16) to an adjusted
      OR of 11.7 (95% CI not reported) (P < .001). Preoperative cognitive impairment
      (adjusted OR, 2.2; 95% CI, 1.4-2.7) was associated with postoperative delirium
      (adjusted OR, 17.0; 95% CI, 1.2-239.8; P < .05). Frailty was associated with a 3-
      to 13-fold increased risk of discharge to a facility (adjusted OR, 3.16 [95% CI,
      1.0-9.99] to 13.02 [95% CI, 5.14-32.98]). CONCLUSIONS AND RELEVANCE: Geriatric
      conditions may be associated with adverse surgical outcomes. A comprehensive
      evaluation of treatment goals and communication of realistic risk estimates are
      essential to guide individualized decision making.

PMID- 24867016
TI  - In Brief: Absorica for acne.

PMID- 24867013
TI  - Effect of endoscopic sphincterotomy for suspected sphincter of Oddi dysfunction
      on pain-related disability following cholecystectomy: the EPISOD randomized
      clinical trial.
AB  - IMPORTANCE: Abdominal pain after cholecystectomy is common and may be attributed
      to sphincter of Oddi dysfunction. Management often involves endoscopic retrograde
      cholangiopancreatography (ERCP) with manometry and sphincterotomy. OBJECTIVE: To
      determine whether endoscopic sphincterotomy reduces pain and whether sphincter
      manometric pressure is predictive of pain relief. DESIGN, SETTING, AND PATIENTS:
      Multicenter, sham-controlled, randomized trial involving 214 patients with pain
      after cholecystectomy without significant abnormalities on imaging or laboratory
      studies, and no prior sphincter treatment or pancreatitis randomly assigned
      (August 6, 2008-March 23, 2012) to undergo sphincterotomy or sham therapy at 7
      referral medical centers. One-year follow-up was blinded. The final follow-up
      visit was March 21, 2013. INTERVENTIONS: After ERCP, patients were randomized 2:1
      to sphincterotomy (n = 141) or sham (n = 73) irrespective of manometry findings.
      Those randomized to sphincterotomy with elevated pancreatic sphincter pressures
      were randomized again (1:1) to biliary or to both biliary and pancreatic
      sphincterotomies. Seventy-two were entered into an observational study with
      conventional ERCP managemeny. MAIN OUTCOMES AND MEASURES: Success of treatment
      was defined as less than 6 days of disability due to pain in the prior 90 days
      both at months 9 and 12 after randomization, with no narcotic use and no further
      sphincter intervention. RESULTS: Twenty-seven patients (37%; 95% CI, 25.9%-48.1%)
      in the sham treatment group vs 32 (23%; 95% CI, 15.8%-29.6%) in the
      sphincterotomy group experienced successful treatment (adjusted risk difference, 
      15.6%; 95% CI, -28.0% to -3.3%; P = .01). Of the patients with pancreatic
      sphincter hypertension, 14 (30%; 95% CI, 16.7%-42.9%) who underwent dual
      sphincterotomy and 10 (20%; 95% CI, 8.7%-30.5%) who underwent biliary
      sphincterotomy alone experienced successful treatment. Thirty-seven treated
      patients (26%; 95% CI,19%-34%) and 25 patients (34%; 95% CI, 23%-45%) in the sham
      group underwent repeat ERCP interventions (P = .22). Manometry results were not
      associated with the outcome. No clinical subgroups appeared to benefit from
      sphincterotomy more than others. Pancreatitis occurred in 15 patients (11%) after
      primary sphincterotomies and in 11 patients (15%) in the sham group. Of the
      nonrandomized patients in the observational study group, 5 (24%; 95% CI, 6%-42%)
      who underwent biliary sphincterotomy, 12 (31%; 95% CI, 16%-45%) who underwent
      dual sphincterotomy, and 2 (17%; 95% CI, 0%-38%) who did not undergo
      sphincterotomy had successful treatment. CONCLUSIONS AND RELEVANCE: In patients
      with abdominal pain after cholecystectomy undergoing ERCP with manometry,
      sphincterotomy vs sham did not reduce disability due to pain. These findings do
      not support ERCP and sphincterotomy for these patients. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT00688662.

PMID- 24867015
TI  - Treating acne with high-dose isotretinoin.

PMID- 24867017
TI  - Surveillance for recurrence of colorectal cancer.

PMID- 24867018
TI  - Surveillance for recurrence of colorectal cancer.

PMID- 24867019
TI  - Trial evidence and approval of therapeutic agents.

PMID- 24867020
TI  - Surveillance for recurrence of colorectal cancer--reply.

PMID- 24867023
TI  - The treatment of acne.

PMID- 24867021
TI  - Trial evidence and approval of therapeutic agents--reply.

PMID- 24867025
TI  - Aortic valve replacement in over 70- and over 80-year olds: 5-year cohort study.
AB  - BACKGROUND: Demand for aortic valve intervention remains high, and together with
      the recent introduction of transcatheter aortic valve implantation, this
      motivates a review of surgical aortic valve replacement in elderly recipients.
      METHODS: Consecutive patients over 70 years of age having isolated aortic valve
      replacement during 2007-11 were retrospectively identified and divided into 70-79
      and >= 80 years age groups for analyses. RESULTS: 62 octogenarians and 121
      septuagenarians were eligible. Among octogenarians, a lower proportion were in
      Canadian Cardiovascular Society angina class 3-4 (3.2% vs. 14.0%, p = 0.022) and
      fewer had diabetes (11.3% vs. 24.8%, p = 0.034), but a higher proportion had
      infective endocarditis (6.5% vs. 0%, p = 0.012), and EuroSCORE II was higher
      (4.9% vs. 3.7%, p < 0.001). Despite this, operative mortality was lower in
      octogenarians (0% vs. 7.4%, p = 0.029), although hospital stay (11.7 vs. 8.9
      days, p = 0.026) was longer. One-, 3-, and 5-year survival rates were 95.2%,
      90.1%, and 75.3% for octogenarians and 89.2%, 81.7%, and 70.2% for
      septuagenarians (p = 0.398). Canadian Cardiovascular Society angina class 3-4 and
      the presence of other valvular stenosis or regurgitation were independent
      predictors of mortality. CONCLUSION: Octogenarians had lower operative mortality
      despite a higher predicted risk preoperatively. Other factors beyond age and
      EuroSCORE, such as frailty, may be important in deciding whether elderly patients
      should undergo aortic valve replacement.

PMID- 24867024
TI  - Alpha-theta effects associated with ageing during the Stroop test.
AB  - The Stroop effect is considered as a standard attentional measure to study
      conflict resolution in humans. The response of the brain to conflict is supposed
      to change over time and it is impaired in certain pathological conditions.
      Neuropsychological Stroop test measures have been complemented with
      electroencephalography (EEG) techniques to evaluate the mechanisms in the brain
      that underlie conflict resolution from the age of 20 to 70. To study the changes
      in EEG activity during life, we recruited a large sample of healthy subjects of
      different ages that included 90 healthy individuals, divided by age into decade
      intervals, which performed the Stroop test while recording a 14 channel EEG. The
      results highlighted an interaction between age and stimulus that was focused on
      the prefrontal (Alpha and Theta band) and Occipital (Alpha band) areas. We
      concluded that behavioural Stroop interference is directly influenced by opposing
      Alpha and Theta activity and evolves across the decades of life. 

PMID- 24867026
TI  - Heart transplant survival rate in Iran: a single-center registry report.
AB  - AIM: to determine 1-month and 1-year survival rate in recipients of heart
      transplants in Imam Khomeini Medical Center. METHODS: we analyzed the outcomes of
      69 patients who underwent heart transplantation between 2007 and 2010. The 1
      month and 1-year survival rates were calculated, and we assessed prognostic
      factors such as donor and recipient age and sex, graft ischemic time during
      surgery, and liver and kidney function tests. RESULTS: increased donor age had a
      significant negative effect on survival rate (p = 0.005). Sex differences between
      donor and recipient had no association with transplant outcome and survival rate.
      The overall 1-month and 1-year survival was 82.6% (n = 54) and 70% (n = 48),
      respectively. CONCLUSION: heart transplantation is a lifesaving procedure for end
      stage heart disorders. Mortality after heart transplantation depends on numerous
      factors, and thus survival rates differ among centers. The 1-month and 1-year
      survival rates after heart transplant in our center currently stand at 82.6% and
      70%, respectively.

PMID- 24867027
TI  - Preoperative levosimendan in ischemic mitral valve repair.
AB  - BACKGROUND: Levosimendan is a new calcium sensitizing drug with vasodilatory and
      inotropic properties, which is used for the treatment of postoperative low
      cardiac output syndrome and difficult weaning from cardiopulmonary bypass.
      OBJECTIVE: To evaluate the hemodynamic effects of levosimendan during and after
      coronary artery bypass grafting on cardiopulmonary bypass and mitral valve repair
      in patients with low left ventricular ejection fractions (<30%). METHODS: 40
      patients were enrolled in this double-blind prospective randomized controlled
      trial. They received either levosimendan or a placebo preoperatively (n = 20) for
      24 h. Clinical parameters were measured before and after administration. Any
      adverse events during and after drug administration and postoperative
      complications were evaluated. RESULTS: Patients treated with levosimendan
      exhibited a higher cardiac index and mean arterial pressure intraoperative and in
      the early postoperative period, compared to the control group. Patients treated
      with levosimendan required less ventilatory support (p < 0.0001) and had shorter
      intensive care unit (p < 0.0001) and hospital stay (p < 0.0001). CONCLUSIONS:
      Preoperative treatment with levosimendan in patients undergoing coronary artery
      bypass grafting and mitral valve repair resulted in improved hemodynamics and a
      stable postoperative course.

PMID- 24867028
TI  - Impact of aortic prosthesis-patient mismatch on left ventricular mass regression.
AB  - BACKGROUND: Prostheses used for aortic valve replacement may be small in relation
      to body size, causing prosthesis-patient mismatch and delaying left ventricular
      mass regression. This study examined the effect of prosthesis-patient mismatch on
      regression of left ventricular mass after aortic valve replacement. METHODS: We
      prospectively studied 96 patients undergoing aortic valve replacement between
      2007 and 2012. Mean and peak gradients and indexed effective orifice area were
      measured by transthoracic echocardiography at 3 and 6 months postoperatively.
      Patient-prosthesis mismatch was defined as indexed effective orifice area <=0.85
      cm(2).m(-2). RESULTS: Moderate prosthesis-patient mismatch was present in 25% of
      patients. There were no significant differences in demographic and operative data
      between patients with and without prosthesis-patient mismatch. Left ventricular
      dimensions, posterior wall thickness, transvalvular gradients, and left
      ventricular mass decreased significantly after aortic valve replacement in both
      groups. The interventricular septal diameter and left ventricular mass index
      regression, and left ventricular ejection fraction were better in patients
      without prosthesis-patient mismatch. There was a significant positive correlation
      between the postoperative indexed effective orifice area of each valve prosthesis
      and the rate of left ventricular mass regression. CONCLUSIONS: Prosthesis-patient
      mismatch leads to higher transprosthetic gradients and impaired left ventricular
      mass regression. A small-sized valve prosthesis does not necessarily result in
      prosthesis-patient mismatch, and may be perfectly adequate in patient with small
      body size.

PMID- 24867029
TI  - C-reactive protein after stroke in arterial hypertension.
AB  - OBJECTIVE: To evaluate the relationship between plasma high-sensitivity C
      reactive protein level and the risk of recurrent coronary and cerebral ischemic
      events after ischemic stroke in patients with arterial hypertension. METHODS: 102
      patients with mild-to-moderate arterial hypertension (67 male, aged 56-68 years)
      were enrolled in the study. Serum high-sensitivity C-reactive protein was
      determined on study entry only. Clinical interviews were performed every 3 months
      during 1 year after blood sampling. Clinical events included confirmed ischemic
      stroke or transient ischemic attack, coronary ischemic events, sudden death,
      diabetes mellitus, and all cardiovascular events including chronic heart failure
      and hospitalization. RESULTS: Patients in the highest quartile of high
      sensitivity C-reactive protein levels had a significantly higher adjusted odds
      ratio for clinical events compared to those in the first quartile (odds ratio =
      7.46, 95% confidence interval: 1.55-19.6, p = 0.001). A receiver operating
      characteristic curve detected a plasma high-sensitivity C-reactive protein cutoff
      level of 5.58 mg.L(-1) (76.7% sensitivity, 80.3% specificity). A Cox regression
      model identified high-sensitivity C-reactive protein >5.58 mg.L(-1) as an
      independent predictor of further cardiovascular events (hazard ratio = 7.14, 95%
      confidence interval: 1.15-12.6, p = 0.009). CONCLUSION: We suggest that high
      sensitivity C-reactive protein levels >5.58 mg.L(-1) strongly predict increased
      risk of cumulative cardiovascular events after ischemic stroke in hypertensive
      patients.

PMID- 24867030
TI  - Clinical impact of diastolic function after surgical ventricular restoration.
AB  - OBJECTIVE: The impact of diastolic function on the clinical outcome of surgical
      ventricular restoration remains controversial. METHODS: 71 patients undergoing
      surgical ventricular restoration between 1999 and 2012 were investigated.
      Perioperative echocardiographic parameters were compared, risk factors for deaths
      and cardiac events were analyzed, and actuarial freedom from death and cardiac
      events was computed. RESULTS: Preoperatively, the left ventricular end-systolic
      volume index was 77 +/- 40 mL.m(-2) and left ventricular ejection fraction was
      33% +/- 11%. Postoperatively, left ventricular systolic function was
      significantly improved (end-systolic volume index 49 +/- 31 mL.m(-2), ejection
      fraction 42.1% +/- 11.7%) with a 33.8% +/- 21.9% reduction in left ventricular
      end-systolic volume index. The transmitral filling deceleration time decreased
      from 198 +/- 54 to 150 +/- 46 ms, and the ratio of early peak filling velocities
      increased significantly postoperatively (from 16 +/- 10 to 21 +/- 17). Freedom
      from death and cardiac events at 5 years was 78% +/- 5% and 64% +/- 6%,
      respectively. Multivariate analyses revealed that age was a significant risk
      factor for all-cause death, postoperative transmitral inflow pattern for cardiac
      death, and preoperative mitral regurgitation and postoperative transmitral inflow
      pattern for cardiac events. CONCLUSION: Despite its positive impact on systolic
      function, surgical ventricular restoration negatively affects postoperative
      diastolic function. Postoperative severe diastolic dysfunction may correlate with
      late mortality and cardiac events.

PMID- 24867032
TI  - Postsplenectomy left lower lobe bronchiectasis.
AB  - BACKGROUND: Bronchiectasis has decreased significantly. I describe a new
      underestimated clinicopathological entity of postsplenectomy left lower lobe
      bronchiectasis. METHODS: This is a retrospective study on 24 patients who had a
      left lower lobectomy for left lower lobe bronchiectasis after splenectomy. The
      mean age was 34.6 years (range 18 to 63 years); there were 19 men and 5 women.
      The available data included history, radiological investigations (ultrasonography
      and computed tomography of the chest and abdomen), operative data, postoperative
      complications, and follow-up data. RESULTS: All patients had a history of
      splenectomy and 10 had undergone subphrenic collection drainage either
      percutaneously or through open drainage a few years prior to the left lower
      lobectomy. Fourteen patients were lost to follow-up. The mean follow-up in 10
      patients was 5.8 years (range 2 to 13 years). CONCLUSIONS: Postsplenectomy left
      lower lobe bronchiectasis is an underestimated clinicopathological entity of
      bronchiectasis. It can be managed by a left lower lobectomy, with acceptable
      results.

PMID- 24867031
TI  - Perioperative predictors of midterm survival after aortic valve replacement.
AB  - BACKGROUND: Elderly patients with aortic stenosis are under-referred for aortic
      valve replacement surgery. This study investigated the perioperative factors
      associated with midterm outcomes in a consecutive series of patients undergoing
      aortic valve replacement with or without coronary artery bypass graft surgery.
      METHODS: From 2006 to 2010, 509 patients having aortic valve replacement or
      aortic valve replacement with coronary artery bypass were grouped according to
      age (<80 years and >=80 years) and procedure (aortic valve replacement +/-
      coronary artery bypass). Patient survival was followed up for 5 years (mean 2.6
      years). Midterm survival was evaluated using Kaplan-Meier and Cox proportional
      hazards regression model statistics. RESULTS AND CONCLUSIONS: 5-year survival
      among octogenarians was 59.2% with an observed 30-day mortality of 1% for aortic
      valve replacement and 3% for aortic valve replacement with coronary artery
      bypass. Kaplan-Meier survival analysis showed that age >=80 years, New York Heart
      Association functional class III/IV, and left ventricular ejection fraction <35%
      were significantly associated with increased midterm mortality. Cox regression
      modeling demonstrated that age >=80 years was the only significant independent
      factor associated with midterm mortality; older patients had a 3-fold increase in
      mortality (adjusted hazard ratio = 3.231, 95% confidence interval: 1.764-5.920, p
      < 0.0001). While hospital and 30-day mortality were not statistically different
      between age groups, age >=80 years was the most powerful predictor of midterm
      death. These results support early aortic valve replacement with or without
      coronary artery bypass in aortic stenosis management.

PMID- 24867033
TI  - Ten cases of resected solitary pulmonary metastases arising from gastric cancer.
AB  - BACKGROUND: Because carcinomatous lymphangitis and carcinomatous pleuritis are
      the usual forms of metastasis associated with gastric cancer, resection of
      solitary pulmonary metastases arising from gastric cancer is rarely performed. To
      clarify the characteristics of pulmonary metastases from gastric cancer, we
      investigated patients who underwent resection of metastatic solitary lung tumors
      arising from gastric cancer. METHODS: Between October 2003 and October 2012, 10
      patients underwent pulmonary metastasectomy for metastatic gastric cancer at our
      institution. We retrospectively evaluated features of the primary gastric cancer
      and the clinicopathological features of the pulmonary metastases in these cases.
      RESULTS: 70% of the patients had stage II disease. Lymphatic invasion was
      observed in all cases of primary gastric cancer. The method of pulmonary
      resection was partial resection in 5 cases, segmentectomy in 1, and lobectomy in
      4. On histopathological examination, immunohistochemical staining was negative
      for thyroid transcription factor-1 and napsin A in all cases. Patients who
      underwent resection of pulmonary metastases arising from gastric cancer had a
      good prognosis: the 4-year survival rate was 75%. CONCLUSIONS: Carefully chosen
      patients have a good opportunity to obtain benefits from resection of pulmonary
      metastases arising from gastric cancer.

PMID- 24867034
TI  - Esophageal diverticula: Analysis of 25 cases.
AB  - BACKGROUND: esophageal diverticula are classified as 2 types: true diverticula
      and pseudodiverticula. These disorders result in clinical manifestations such as
      dysphagia and esophageal reflux. In this study, we evaluated the results of
      surgical treatment for diverticula. METHODS: all patients suffering from
      symptomatic esophageal diverticulum, who underwent surgical treatment in Ghaem
      Hospital from 2000 to 2012 and were followed up for at least for one year, were
      included in the study. Age, sex, clinical manifestations, location, surgical
      approach, and mortality were evaluated. There were 25 patients (15 men and 10
      women) with a mean age of 41 +/- 8.3 years. RESULTS: the most common site of
      involvement was inferior (epiphrenic diverticulum). Barium swallow was
      diagnostic. After surgical treatment, complications occurred in 4 (16%) patients,
      comprising anastomosis site leakage, hoarseness, atelectasis, and wound
      infection; all were treated medically. There was no postoperative mortality. All
      patients experienced an improvement in symptoms during one year of follow-up.
      CONCLUSION: due to the good results and minimal complications postoperatively,
      surgical treatment is recommended for patients with symptomatic esophageal
      diverticulum.

PMID- 24867035
TI  - Giant left ventricular fibroma presenting as ventricular tachycardia in a child.
AB  - We present a rare case of giant left ventricular apical fibroma presenting as
      recurrent ventricular tachycardia in a 14-month-old girl. The diagnosis was made
      by echocardiography and chest computed tomography, and confirmed by
      histopathology. The fibroma was resected surgically, and the patient followed up
      for 4 years. 

PMID- 24867036
TI  - Heyde's syndrome.
AB  - Gastrointestinal bleeding due to colonic angiodysplasia can be associated with
      calcified aortic stenosis. This association is referred to as Heyde's syndrome.
      Aortic valve replacement can prevent recurrent gastrointestinal bleeding in these
      cases. We describe the case of a 46-year-old woman with congestive heart failure
      related to aortic stenosis, and severe anemia, with multiple angiodysplasias on
      the ileum and colon. After aortic valve replacement, there were no further
      episodes of bleeding and her hemoglobin levels normalized. 

PMID- 24867037
TI  - Giant coronary artery fistula.
AB  - Giant coronary artery fistula is rare. We describe the diagnostic work-up and
      surgical management of a 55-year-old woman who presented with congestive heart
      failure caused by a giant coronary artery fistula from the left circumflex artery
      to the coronary sinus. 

PMID- 24867038
TI  - Direct closure of an asymptomatic right coronary sinus of Valsalva aneurysm.
AB  - A 52-year-old man was referred for evaluation of palpitation. Transthoracic
      echocardiography revealed an extracardiac aneurysm of the right coronary sinus of
      Valsalva, and normal anatomy of the aortic valve with no regurgitation. Three
      dimensional computed tomography confirmed the aneurysm with a diameter of 21 *
      13.7 mm arising from the right coronary sinus of Valsalva under the right
      coronary artery. Surgical repair was performed without changing the normal
      anatomy of the aortic valve, preserving the right coronary ostium. Intraoperative
      and postoperative echocardiography showed complete closure of the aneurysm with
      normal functioning of the aortic valve. 

PMID- 24867039
TI  - Complete right ventricular obstruction caused by a giant cardiac myxoid sarcoma.
AB  - Myxoid sarcoma is a very rare variant of primary malignant sarcoma of the heart,
      which presents like a myxoma. We describe the case of 21-year-old man with a
      giant myxoid sarcoma occupying most of the right ventricle. He underwent
      emergency surgery to resect the tumor and replace the tricuspid valve which was
      infiltrated. Chemotherapy and radiotherapy were given postoperatively. 

PMID- 24867040
TI  - A large neglected pleomorphic adenoma of the lung: Report of a rare case.
AB  - Primary pleomorphic adenomas of the lung are very rare tumors that have peculiar
      clinical and oncologic features. We report here on the diagnostic and therapeutic
      approach for a patient with a large neglected pulmonary pleomorphic adenoma that
      presented initially as pneumonia. 

PMID- 24867041
TI  - An unusual case of mediastinal mass and bilateral nodules.
AB  - A 23-year-old woman presented with a mediastinal paraganglioma and multiple
      pulmonary chondromas following antral gastric resection for gastrointestinal
      stromal tumor. These tumors form the Carney triad, a rare disorder of unknown
      genetic background. First described in 1977, approximately 120 cases have been
      documented in the literature. The tumors do not harbor the specific c-kit or
      PDGFRA gene mutations often found in sporadic gastrointestinal stromal tumor. In
      most cases, gastric gastrointestinal stromal tumor is the first tumor to be
      detected, with secondary tumors appearing years later. Even if it is rare, Carney
      triad should be suspected in young patients with history of gastrointestinal
      stromal tumor. 

PMID- 24867042
TI  - Transcatheter valve implantation in a stenosed quadricuspid aortic valve.

PMID- 24867043
TI  - Three-dimensional echocardiographic evaluation of acute aortic dissection.

PMID- 24867044
TI  - Gastrointestinal hemorrhage caused by aortoenteric fistula due to aortic
      aneurysm.

PMID- 24867045
TI  - Quadricuspid aortic valve.

PMID- 24867046
TI  - Complex bilateral upper lobe aspergilloma.

PMID- 24867047
TI  - Pleural thoracic splenosis 17 years after thoracoabdominal blunt trauma.

PMID- 24867048
TI  - A case of a large cardiac lipoma with coronary artery disease.
AB  - Cardiac lipomas are extremely rare benign tumors. They usually remain
      asymptomatic and are detected incidentally. We report an unusual case of a 60
      year-old man who presented with a large epicardial lipoma found unexpectedly
      during coronary artery examinations. Coronary angiography revealed advanced 3
      vessel coronary artery disease. We successfully performed simultaneous curative
      surgery for the large cardiac lipoma and coronary artery bypass grafting.
      Histopathology confirmed the diagnosis of lipoma; it weighed 450 g and had a
      stalk connected to the left atrium. 

PMID- 24867049
TI  - Surgery for an adult with tetralogy of Fallot and acquired heart disease.
AB  - We experienced the rare case of an elderly woman with uncorrected tetralogy of
      Fallot. She also had significant mitral and tricuspid regurgitation with
      deteriorated ventricular function and ischemic coronary artery disease. We
      performed a radical repair of the tetralogy of Fallot, valvular operations for
      the mitral and tricuspid regurgitation, and coronary artery bypass grafting.
      Although mechanical circulatory support was required postoperatively, she
      recovered well to New York Heart Association functional class II. 

PMID- 24867050
TI  - A case of incomplete Carney's triad.
AB  - A 62-year-old woman, who had multiple pulmonary nodules noted 6 years earlier,
      and surgery for a gastrointestinal stromal tumor 2 years earlier, was found to
      have enlargement of her pulmonary nodules. Surgery was selected to make a
      definite diagnosis. Thoracoscopic segmentectomy of right segments 9 and 10 was
      performed, and pulmonary chondroma was diagnosed. Carney designated the
      combination of 3 rare soft tissue tumors (gastric leiomyosarcoma, pulmonary
      chondroma, and extraadrenal paraganglioma) as a syndrome. This patient may have
      had an incomplete type of Carney's triad with 2 lesions in the stomach and lung. 

PMID- 24867051
TI  - Breast cancer immunotherapy: monoclonal antibodies and peptide-based vaccines.
AB  - Recently, immunotherapy has emerged as a treatment strategy in the adjuvant
      setting of breast cancer. In this review, monoclonal antibodies in passive and
      peptide-based vaccines, as one of the most commonly studied in active
      immunotherapy approaches, are discussed. Trastuzumab, a monoclonal antibody
      against HER-2/neu, has demonstrated considerable efficacy. However, resistance to
      trastuzumab has led to development of many targeted therapies which have been
      examined in clinical trials. Monoclonal antibodies against immune-checkpoint
      molecules that are dysregulated by tumors as an immune resistance mechanism are
      also explained in this review. Additionally, monoclonal antibodies with the
      ability to target breast cancer stem cells that play a role in cancer recurrence
      are mentioned. Here, clinical trials of HER-2/neu B and T cells, MUC1 and hTERT
      cancer peptide vaccines are also presented. In addition, various strategies for
      enhancing vaccine efficacy including combination with monoclonal antibodies and
      using different delivery systems for peptide/protein-based vaccine are described.

PMID- 24867052
TI  - 'Psychotropics caught in a trap' - adopting a screening approach to specific
      needs.
AB  - In the field of forensic toxicology, numerous strategies using different types of
      LC-MS platforms have been developed to set up an ultimate comprehensive screening
      method. Despite all this research, the question for the detection of a dedicated
      set of substances arises quite often in daily routine work. In this project, a
      screening method for the detection of psychotropic drugs based on the open
      library concept of a recently developed LC-MS(n) screening approach was developed
      and the effectiveness of a heated ESI-source was evaluated. To set up an
      individual spectral library all available data of psychotropics from the
      ToxtyperTM library was transferred to a new library format and complemented by
      MS, MS(2) and MS(3) data of additional psychotropic compounds. Precursor masses
      and retention time information of the library were used to trigger data dependent
      acquisition of MS(n)-spectra. Serum samples were analysed after alkaline liquid
      liquid extraction on a Dionex RSLC (AcclaimTM C18 100*2.1C) coupled to a Bruker
      amaZon speed ion trap. A conventional ESI-source and an ionBoosterTM source (IB)
      were used for ionization. All other LC and MS parameters were adopted from the
      original screening approach. Identification and result reporting was carried out
      by a fully automated software script. This screening method finally contains the
      individual precursor mass and retention time of 105 psychotropic substances and
      metabolites. Method evaluation was performed using pooled serum samples fortified
      with 12 different mixtures containing a total of 99 compounds at low therapeutic
      concentrations (cLOW and 2*cLOW). The customized method (ESI/IB) led to a higher
      rate of identifications (92%) - especially at low concentration levels (cLOW) -
      as the comprehensive screening approach (87%). Results from routine analysis with
      known intake of psychotropic drugs were confirmed with positive findings, if the
      concentration range was above or around the assumed limit of detection from this
      evaluation study. The Toxtyper open library concept enables fast and easy
      generation of new screening methods. The generated screening method is a fast and
      robust tool for the detection and identification of 105 psychotropics in human
      serum. Use of the ionBooster source led to a significant increase of the
      ionization efficiency within this sort of substance class. Evaluation in spiked
      human serum samples showed detection of low therapeutic levels for the majority
      of compounds, making the screening applicable for clinical and forensic samples
      (intoxication and post mortem cases). 

PMID- 24867053
TI  - An unusual case of non-fatal poisoning due to herbicide 4-chloro-2-methyl
      phenoxyacetic acid (MCPA).
AB  - MCPA (4-chloro-2-methyl phenoxyacetic acid) is a systemic hormone-type selective
      herbicide readily absorbed by leaves and roots. Use of MCPA for murder or
      attempted murder is very rare in Sri Lanka. However, a reported case of attempted
      murder by adding MCPA to water will be discussed in this paper. Three extraction
      methods were carried out with urine samples spiked with MCPA, namely liquid
      liquid extraction with chloroform, solid phase extraction using C18 cartridges
      and vortex mixing with methanolic hydrochloric acid. Based on the recovery
      results, solid phase extraction was selected as the most suitable method and
      applied in the analysis of urine and water samples. Identification of MCPA in
      urine, water and the suspected poison bottle was carried out by HPLC and was
      confirmed by GC-MS. 4-chloro -2- methyl phenol metabolite was also identified and
      confirmed in the urine sample of the patient by GC-MS. Quantitative analysis of
      MCPA was carried out by HPLC using a validated method where Zorbax XDB-C18 column
      was used with photo diode array detector. In this case, presence of MCPA in one
      patient's urine sample collected four days after the incident was confirmed by GC
      MS and found at a concentration of 0.83MUg/ml. MCPA was not identified in the
      urine samples collected after 13 days in other three patients. The water sample
      taken from the suspected water storage tank found to contain 101MUg/ml of MCPA.
      The results showed that HPLC combined with GC-MS is suitable for forensic
      analysis of MCPA in urine. 

PMID- 24867054
TI  - Neonatal resuscitation in resource-limited settings: titrating oxygen delivery
      without an oxygen blender.
AB  - OBJECTIVE: To test whether 4 commonly used self-inflating bags with a reservoir
      in situ can reliably deliver different oxygen concentrations (21%-100%) using a
      portable oxygen cylinder with flows of <=5 L/min. STUDY DESIGN: Four self
      inflating bags (from Laerdal, Ambu, Parker Healthcare, and Mayo Healthcare) were
      tested to provide positive pressure ventilation to a manikin at 60 inflations/min
      by 4 operators. Oxygen delivery was measured for 2 minutes, combining oxygen
      flows (0.25, 0.5, 1, 5 L/min) and peak inspiratory pressures (PIPs 20-25, 35-40
      cmH2O). RESULTS: Combinations (n=128) were performed twice. Oxygen delivery
      depended upon device, oxygen flow, and PIP. All self-inflating bags delivered
      mean oxygen concentrations of <40% with 0.25 L/min, regardless of PIP. Three self
      inflating bags delivered <=40% with flow 0.5 L/min at PIP 35-40 cmH2O, whereas
      all delivered >40% at PIP 20-25 cmH2O. With 1 L/min, 3 self-inflating bags
      delivered 40%-60% at PIP 35-40 cmH2O and all delivered >60% at PIP 20-25 cmH2O.
      With 5 L/min, all self-inflating bags delivered close to or 100%, regardless of
      PIP. Differences in oxygen delivery between self-inflating bags were
      statistically significant (P<.001) even when differences were not clinically
      important. CONCLUSION: Self-inflating bags with a reservoir in situ can deliver a
      variety of oxygen concentrations without a blender, from <40% with 0.25 L/min
      oxygen flow to 100% with 5 L/min. The adjustment of oxygen flow may be a useful
      method of titrating oxygen in settings where air-oxygen blenders are unavailable.

PMID- 24867055
TI  - The use of UV/ozone-treated MoS2 nanosheets for extended air stability in organic
      photovoltaic cells.
AB  - MoS2 nanosheets obtained through a simple sonication exfoliation method are
      employed as a hole-extraction layer (HEL) to improve the efficiency and air
      stability of organic photovoltaic cells (OPVs). The reduction in the wavenumber
      difference, appearance of a UV-vis peak, and atomic force microscopy images
      indicate that MoS2 nanosheets are formed through the sonication method. The OPVs
      with MoS2 layers show a degraded performance with a power conversion efficiency
      (PCE) of 1.08%, which is lower than that of OPVs without HEL (1.84%). After
      performing the UV/ozone (UVO) treatment of the MoS2 surface for 15 min, the PCE
      value increases to 2.44%. Synchrotron radiation photoelectron spectroscopy data
      show that the work function of MoS2 increases from 4.6 to 4.9 eV upon UVO
      treatment, suggesting that the increase in the PCE value is caused by the bandgap
      alignment. Upon inserting poly(3,4-ethylenedioxythiophene):poly(styrene
      sulfonate) (PEDOT:PSS) between MoS2 and the active layer, the PCE value of the
      OPV increases to 2.81%, which is comparable with that of the device employing
      only PEDOT:PSS. Furthermore, the stability of the OPVs is improved significantly
      when MoS2/PEDOT:PSS layers are used as the HEL. Therefore, it is considered that
      the use of UVO-treated MoS2 may improve the stability of OPV cells without
      degrading the device performance. 

PMID- 24867056
TI  - Language outcomes for children with cochlear implants enrolled in different
      communication programs.
AB  - OBJECTIVES: The aims of this study were to (a) compare language outcomes in
      pediatric cochlear implant users enrolled in three different communication
      programs: sign and spoken language, auditory-oral, and auditory-verbal therapy,
      and (b) examine factors influencing language outcomes. METHODS: Post-implant
      standard scores on language assessments of receptive vocabulary, auditory
      comprehension, and expressive communication were collected from files of 42
      children with prelingual hearing loss who were implanted by 3;6 years of age.
      Early intervention history, device details, and demographic information were
      obtained for each child. Family involvement was evaluated using a rating scale.
      RESULTS: After adjusting for potential covariates, there were no significant
      differences in language outcomes across the three groups. Overall, there was a
      large degree of variability with some children achieving below average scores and
      others achieving above average scores. Age at diagnosis of hearing loss and
      family involvement were significantly associated with language outcomes.
      CONCLUSION: Regardless of the type of communication approach received, children
      diagnosed with hearing loss at an early age and children with a high level of
      family involvement had better post-implant language scores than children
      diagnosed later and with lower levels of family involvement. These findings
      emphasize the importance of early diagnosis and highlight the contribution
      families make to the language outcomes of children with cochlear implants.

PMID- 24867057
TI  - Conceptual development of "at-homeness" despite illness and disease: a review.
AB  - Only one empirical study, the one by Zingmark, Norberg and Sandman published in
      1995, explicitly focuses on at-homeness, the feeling of being metaphorically at
      home, as a particular aspect of wellness. However, other studies reveal aspects
      of at-homeness, but if or how such aspects of at-homeness are related to each
      other is unclear. For this reason, the aim was to review Scandinavian nursing
      research related to at-homeness in the context of wellness-illness in severe and
      long-term conditions in order to take a step towards conceptual clarification of
      "at-homeness." The review included interpretive studies related to severe and
      long-term illness conducted in Sweden: 10 original articles and 5 doctoral
      theses. "At-homeness" was found to be a contextually related meaning of wellness
      despite illness and disease embedded in the continuum of being metaphorically at
      home and metaphorically homeless. This was characterized by three interrelated
      aspects and four processes: being safe through expanding-limiting experiences of
      illness and time, being connected through reunifying-detaching ways of relating,
      and being centred through recognition-non-recognition of oneself in the
      experience and others giving-withdrawing a place for oneself. This
      conceptualization is to be regarded as a step in conceptual clarification.
      Further empirical investigation and theoretical development of "at-homeness" are
      needed. The conceptualization will be a step of plausible significance for the
      evaluation of interventions aimed at enhancing wellness for people with severe
      long-term illness, such as the frail elderly, and people with chronic illness or
      palliative care needs. 

PMID- 24867060
TI  - Functional response of Euseius concordis to densities of different developmental
      stages of the cassava green mite.
AB  - Both prey density and developmental stage of pests and natural enemies are known
      to influence the effectiveness of biological control. However, little is known
      about the interaction between prey density and population structure on predation
      and fecundity of generalist predatory mites. Here, we evaluated the functional
      response (number of prey eaten by predator in relation to prey density) of adult
      females and nymphs of the generalist predatory mite Euseius concordis to
      densities of different developmental stages of the cassava green mite
      Mononychellus tanajoa, as well as the fecundity of adult females of the predator.
      We further assessed the instantaneous rate of increase, based on fecundity and
      mortality, of E. concordis fed on eggs, immatures and adults of M. tanajoa.
      Overall, nymphs and adults of E. concordis feeding on eggs, immatures and females
      of M. tanajoa had a type III functional response curve suggesting that the
      predator increased prey consumption rate as prey density increased. Both nymphs
      and adult females of the predator consumed more eggs than immatures of M. tanajoa
      from the density of 20 items per leaf disc onwards, revealing an interaction
      between prey density and developmental stage in the predatory activity of E.
      concordis. In addition, population growth rate was higher when the predator fed
      on eggs and immatures in comparison with females. Altogether our results suggest
      that E. concordis may be a good candidate for the biological control of M.
      tanajoa populations. However, the efficiency of E. concordis as a biological
      control agent of M. tanajoa is contingent on prey density and population
      structure. 

PMID- 24867061
TI  - Potential lethal and non-lethal effects of predators on dispersal of spider
      mites.
AB  - Predators can affect prey dispersal lethally by direct consumption or non
      lethally by making prey hesitate to disperse. These lethal and non-lethal effects
      are detectable only in systems where prey can disperse between multiple patches.
      However, most studies have drawn their conclusions concerning the ability of
      predatory mites to suppress spider mites based on observations of their
      interactions on a single patch or on heavily infested host plants where spider
      mites could hardly disperse toward intact patches. In these systems, specialist
      predatory mites that penetrate protective webs produced by spider mites quickly
      suppress the spider mites, whereas generalist predators that cannot penetrate the
      webs were ineffective. By using a connected patch system, we revealed that a
      generalist ant, Pristomyrmex punctatus Mayr (Hymenoptera: Formicidae),
      effectively prevented dispersal of spider mites, Tetranychus kanzawai Kishida
      (Acari: Tetranychidae), by directly consuming dispersing individuals. We also
      revealed that a generalist predatory mite, Euseius sojaensis Ehara (Acari:
      Phytoseiidae), prevented between-patch dispersal of T. kanzawai by making them
      hesitate to disperse. In contrast, a specialist phytoseiid predatory mite,
      Neoseiulus womersleyi Schicha, allowed spider mites to escape an initial patch,
      increasing the number of colonized patches within the system. Our results suggest
      that ants and generalist predatory mites can effectively suppress Tetranychus
      species under some conditions, and should receive more attention as agents for
      conservation biological control in agroecosystems. 

PMID- 24867062
TI  - The effect of temperature on basal tension and thyroarytenoid muscle contraction
      in an isolated rat glottis model.
AB  - The pitch of voice is closely related to the vocal fold tension, which is the end
      result of coordinated movement of the intralaryngeal muscles, and especially the
      thyroarytenoid muscle. It is known that vocal quality may be affected by
      surrounding temperature; however, the effect of temperature on vocal fold tension
      is mostly unknown. Thus, the aim of this study was to evaluate the effect of
      temperature on isolated rat glottis and thyroarytenoid muscle contraction induced
      by electrical field stimulation. In vitro isometric tension of the glottis ring
      from 30 Sprague-Dawley rats was continuously recorded by the tissue bath method.
      Electrical field stimulation was applied to the glottis ring with two wire
      electrodes placed parallel to the glottis and connected to a direct-current
      stimulator. The tension changes of the rat glottis rings that were either
      untreated or treated with electrical field stimulation were recorded continuously
      at temperatures from 37 to 7  degrees C or from 7 to 37  degrees C. Warming from
      7 to 37  degrees C increased the basal tension of the glottis rings and decreased
      the electrical field stimulation-induced glottis ring contraction, which was
      chiefly due to thyroarytenoid muscle contraction. In comparison, cooling from 37
      to 7  degrees C decreased the basal tension and enhanced glottis ring contraction
      by electrical field stimulation. We concluded that warming increased the basal
      tension of the glottis in vitro and decreased the amplitude of electrical field
      stimulation-induced thyroarytenoid muscle contraction. Thus, vocal pitch and the
      fine tuning of vocal fold tension might be affected by temperature in vivo.

PMID- 24867065
TI  - A hantavirus pulmonary syndrome (HPS) DNA vaccine delivered using a spring
      powered jet injector elicits a potent neutralizing antibody response in rabbits
      and nonhuman primates.
AB  - Sin Nombre virus (SNV) and Andes virus (ANDV) cause most of the hantavirus
      pulmonary syndrome (HPS) cases in North and South America, respectively. The
      chances of a patient surviving HPS are only two in three. Previously, we
      demonstrated that SNV and ANDV DNA vaccines encoding the virus envelope
      glycoproteins elicit high-titer neutralizing antibodies in laboratory animals,
      and (for ANDV) in nonhuman primates (NHPs). In those studies, the vaccines were
      delivered by gene gun or muscle electroporation. Here, we tested whether a
      combined SNV/ANDV DNA vaccine (HPS DNA vaccine) could be delivered effectively
      using a disposable syringe jet injection (DSJI) system (PharmaJet, Inc).
      PharmaJet intramuscular (IM) and intradermal (ID) needle-free devices are FDA
      510(k)-cleared, simple to use, and do not require electricity or pressurized gas.
      First, we tested the SNV DNA vaccine delivered by PharmaJet IM or ID devices in
      rabbits and NHPs. Both IM and ID devices produced high-titer anti-SNV
      neutralizing antibody responses in rabbits and NHPs. However, the ID device
      required at least two vaccinations in NHP to detect neutralizing antibodies in
      most animals, whereas all animals vaccinated once with the IM device
      seroconverted. Because the IM device was more effective in NHP, the Stratis((r))
      (PharmaJet IM device) was selected for follow-up studies. We evaluated the HPS
      DNA vaccine delivered using Stratis((r)) and found that it produced high-titer
      anti-SNV and anti-ANDV neutralizing antibodies in rabbits (n=8/group) as measured
      by a classic plaque reduction neutralization test and a new pseudovirion
      neutralization assay. We were interested in determining if the differences
      between DSJI delivery (e.g., high-velocity liquid penetration through tissue) and
      other methods of vaccine injection, such as needle/syringe, might result in a
      more immunogenic DNA vaccine. To accomplish this, we compared the HPS DNA vaccine
      delivered by DSJI versus needle/syringe in NHPs (n=8/group). We found that both
      the anti-SNV and anti-ANDV neutralizing antibody titers were significantly higher
      (p-value 0.0115) in the DSJI-vaccinated groups than the needle/syringe group. For
      example, the anti-SNV and anti-ANDV PRNT50 geometric mean titers (GMTs) were
      1,974 and 349 in the DSJI-vaccinated group versus 87 and 42 in the needle/syringe
      group. These data demonstrate, for the first time, that a spring-powered DSJI
      device is capable of effectively delivering a DNA vaccine to NHPs. Whether this
      HPS DNA vaccine, or any DNA vaccine, delivered by spring-powered DSJI will elicit
      a strong immune response in humans, requires clinical trials. 

PMID- 24867063
TI  - Cartilage tissue engineering using dermis isolated adult stem cells: the use of
      hypoxia during expansion versus chondrogenic differentiation.
AB  - Dermis isolated adult stem (DIAS) cells, a subpopulation of dermis cells capable
      of chondrogenic differentiation in the presence of cartilage extracellular
      matrix, are a promising source of autologous cells for tissue engineering.
      Hypoxia, through known mechanisms, has profound effects on in vitro
      chondrogenesis of mesenchymal stem cells and could be used to improve the
      expansion and differentiation processes for DIAS cells. The objective of this
      study was to build upon the mechanistic knowledge of hypoxia and translate it to
      tissue engineering applications to enhance chondrogenic differentiation of DIAS
      cells through exposure to hypoxic conditions (5% O2) during expansion and/or
      differentiation. DIAS cells were isolated and expanded in hypoxic (5% O2) or
      normoxic (20% O2) conditions, then differentiated for 2 weeks in micromass
      culture on chondroitin sulfate-coated surfaces in both environments. Monolayer
      cells were examined for proliferation rate and colony forming efficiency.
      Micromasses were assessed for cellular, biochemical, and histological properties.
      Differentiation in hypoxic conditions following normoxic expansion increased per
      cell production of collagen type II 2.3 fold and glycosaminoglycans 1.2 fold
      relative to continuous normoxic culture (p<0.0001). Groups expanded in hypoxia
      produced 51% more collagen and 23% more GAGs than those expanded in normoxia
      (p<0.0001). Hypoxia also limited cell proliferation in monolayer and in 3D
      culture. Collectively, these data show hypoxic differentiation following normoxic
      expansion significantly enhances chondrogenic differentiation of DIAS cells,
      improving the potential utility of these cells for cartilage engineering. 

PMID- 24867066
TI  - BTX AgilePulse(TM) system is an effective electroporation device for
      intramuscular and intradermal delivery of DNA vaccine.
AB  - DNA vaccines promote immune system activation in small animals and exhibit
      certain advantages when compared to conventional recombinant protein vaccines.
      However in clinical trials DNA vaccines are less effective in inducing potent
      immune responses due to the low delivery efficiency and expression of antigens.
      Currently, various delivery devices such as gene-guns, bioinjectors and
      electroporation systems are being used in order to increase the potency of DNA
      vaccines. However, the optimal delivery parameters are required and must be
      carefully set to obtain the highest levels of gene expression and strong immune
      responses in humans. The focus of this study was to optimize electroporation
      settings (voltage, pulse length, pulse intervals, and number of pulses), as well
      as the route of administration (intradermal vs. intramuscular) and dosage of the
      DNA epitope vaccine, AV-1959D, delivered by the BTX AgilePulse(TM) system. As a
      result, we have chosen the optimal settings for electroporation delivery using
      different routes of immunization with this vaccine, generating (i) robust
      antibody production to the B cell epitope (a small peptide, derived from beta
      amyloid), and (ii) strong cellular immune responses to Th epitopes (a small
      synthetic peptide and eleven peptides from various pathogens) incorporated into
      DNA vaccine platform. 

PMID- 24867068
TI  - Potential benefit of dehydroepiandrosterone supplementation for infertile but not
      poor responder patients in a IVF program.
AB  - AIM: The aim of this paper was to evaluate the hypothesis that pretreatment with
      dehydroepiandrosterone (DEHA) may improve the result on in vitro fertilization
      (IVF) and the pregnancy outcome among infertile women with normal ovarian
      reserve. METHODS: Double-blind, randomized, placebo-controlled study; 52
      infertile patients received the long protocol IVF. Patients in Group 1, received
      75 mg of DHEA once a day, 8 weeks before starting the IVF cycle and during
      treatment; control group (Group 2) received placebo. The primary endpoint was
      pregnancy, live birth and miscarriage rates, secondary endpoint was standard IVF
      parameters such us stimulation duration (hCG day), E2 on HCG-day, endometrial
      thickness, number of retrieved oocytes, metaphase II oocytes, embryos transferred
      and score of leading embryos transferred. RESULTS: Patients in the DHEA group had
      a significantly higher live birth rate compared with controls (P<0.05).
      Miscarriage rate was higher in control group (P<0.05). CONCLUSION: DHEA
      supplementation could have a beneficial effect on IVF outcome in infertile women
      with normal ovarian reserve.

PMID- 24867071
TI  - Dynamic evolution of cross-correlations in the Chinese stock market.
AB  - The analysis of cross-correlations is extensively applied for the understanding
      of interconnections in stock markets and the portfolio risk estimation. Current
      studies of correlations in Chinese market mainly focus on the static correlations
      between return series, and this calls for an urgent need to investigate their
      dynamic correlations. Our study aims to reveal the dynamic evolution of cross
      correlations in the Chinese stock market, and offer an exact interpretation for
      the evolution behavior. The correlation matrices constructed from the return
      series of 367 A-share stocks traded on the Shanghai Stock Exchange from January
      4, 1999 to December 30, 2011 are calculated over a moving window with a size of
      400 days. The evolutions of the statistical properties of the correlation
      coefficients, eigenvalues, and eigenvectors of the correlation matrices are
      carefully analyzed. We find that the stock correlations are significantly
      increased in the periods of two market crashes in 2001 and 2008, during which
      only five eigenvalues significantly deviate from the random correlation matrix,
      and the systemic risk is higher in these volatile periods than calm periods. By
      investigating the significant contributors of the deviating eigenvectors in
      different time periods, we observe a dynamic evolution behavior in business
      sectors such as IT, electronics, and real estate, which lead the rise (drop)
      before (after) the crashes. Our results provide new perspectives for the
      understanding of the dynamic evolution of cross-correlations in the Chines stock
      markets, and the result of risk estimation is valuable for the application of
      risk management. 

PMID- 24867069
TI  - Effect of oral nutritional supplementation on wound healing in diabetic foot
      ulcers: a prospective randomized controlled trial.
AB  - AIMS: Among people with diabetes, 10-25% will experience a foot ulcer. Research
      has shown that supplementation with arginine, glutamine and beta-hydroxy-beta
      methylbutyrate may improve wound repair. This study tested whether such
      supplementation would improve healing of foot ulcers in persons with diabetes.
      METHODS: Along with standard of care, 270 subjects received, in a double-blinded
      fashion, (twice per day) either arginine, glutamine and beta-hydroxy-beta
      methylbutyrate or a control drink for 16 weeks. The proportion of subjects with
      total wound closure and time to complete healing was assessed. In a post-hoc
      analysis, the interaction of serum albumin or limb perfusion, as measured by
      ankle-brachial index, and supplementation on healing was investigated. RESULTS:
      Overall, there were no group differences in wound closure or time to wound
      healing at week 16. However, in subjects with an albumin level of <= 40 g/l
      and/or an ankle-brachial index of < 1.0, a significantly greater proportion of
      subjects in the arginine, glutamine and beta-hydroxy-beta-methylbutyrate group
      healed at week 16 compared with control subjects (P = 0.03 and 0.008,
      respectively). Those with low albumin or decreased limb perfusion in the
      supplementation group were 1.70 (95% CI 1.04-2.79) and 1.66 (95% CI 1.15-2.38)
      times more likely to heal. CONCLUSIONS: While no differences in healing were
      identified with supplementation in non-ischaemic patients or those with normal
      albumin, addition of arginine, glutamine and beta-hydroxy-beta-methylbutyrate as
      an adjunct to standard of care may improve healing of diabetic foot ulcers in
      patients with risk of poor limb perfusion and/or low albumin levels. Further
      investigation involving arginine, glutamine and beta-hydroxy-beta-methylbutyrate
      in these high-risk subgroups might prove clinically valuable.

PMID- 24867072
TI  - Transition metal complexes of neocryptolepine analogues. Part I: synthesis,
      spectroscopic characterization, and invitro anticancer activity of copper(II)
      complexes.
AB  - New generation of copper(II) complexes with aminoalkylaminoneocryptolepine as
      bidentate ligands has been synthesized and it is characterized by elemental
      analyses, magnetic moment, spectra (IR, UV-Vis, (1)H NMR and ESR) and thermal
      studies. The IR data suggest the coordination modes for ligands which behave as a
      bidentate with copper(II) ion. Based on the elemental analysis, magnetic studies,
      electronic and ESR data, binuclear square planar geometry was proposed for
      complexes 7a, 7b, square pyramidal for 9a, 9b and octahedral for 8a, 8b, 10a,
      10b. The molar conductance in DMF solution indicates that all complexes are
      electrolyte except 7a and 7b. The ESR spectra of solid copper(II) complexes in
      powder form showed an axial symmetry with (2)B1g as a ground state and hyperfine
      structure. The thermal stability and degradation of the ligands and their metal
      complexes were studied employing DTA and TG methods. The metal-free ligands and
      their copper(II) complexes were tested for their in vitro anticancer activity
      against human colon carcinoma (HT-29). The results showed that the synthesized
      copper(II) complexes exhibited higher anticancer activity than their free
      ligands. Of all the studied copper(II) complexes, the bromo-substituted complex
      9b exhibited high anticancer activity at low micromolar inhibitory concentrations
      (IC50=0.58MUM), compared to the other complexes and the free ligands. 

PMID- 24867074
TI  - Tobacco cessation education for advanced practice nurses.
AB  - The predicted shortfall of primary care physicians and the millions of newly
      insured beginning in 2014 call for an increase in the number of advanced practice
      nurses (APRNs). Advanced practice nurses can significantly improve their clients'
      quality of life and increase their life expectancy through tobacco cessation
      education. The purpose of this study was to educate APRN students on smoking
      information and techniques to assist clients with quitting smoking in the primary
      care setting. 

PMID- 24867075
TI  - Nursing faculty knowledge of the Americans with Disabilities Act.
AB  - A survey was conducted to assess nursing faculty (n=231) knowledge of the
      Americans With Disabilities Act requirements. Only 21% (n=46) of the participants
      received a passing score of 78%. While 76% (n=161) knew that students must
      provide documentation of a disability to receive accommodation, 49% (n=104) did
      not recognize that an individual faculty member may be held personally liable if
      he/she fails to provide accommodation. Participants' knowledge of the Act was low
      and could create barriers to student success.

PMID- 24867076
TI  - Longitudinal study of stress, self-care, and professional identity among nursing
      students.
AB  - This longitudinal study describes the factors associated with the acquisition of
      a professional identity over the course of prelicensure education among 45
      baccalaureate nursing students. At every time point, personal spiritual growth
      practices and the students' perceptions of their caring abilities predicted sense
      of fit with the profession. Even as there is a growing emphasis of quality and
      safety education, caring and spirituality remain central to nurses' professional
      identities on entry to practice. 

PMID- 24867078
TI  - WIN55,212-2 impairs non-associative recognition and spatial memory in rats via
      CB1 receptor stimulation.
AB  - Endogenous and exogenous cannabinoids modulate learning and memory primarily via
      the cannabinoid type 1 receptor (CB1R). A variety of experimental procedures has
      focused on the role of CB1R in various aspects of learning and memory processes.
      However, the picture still remains unclear as there is a lack of information on
      the effects of relatively low doses of CB1R agonists in relation to their effects
      on locomotion. The present study sought to investigate CB1R activation, using a
      range of relatively low doses of the CB1R agonist WIN55,212-2, on multiple
      aspects of learning and memory in rats. For this purpose, non-associative
      learning was examined using the habituation of locomotion paradigm, recognition
      memory was evaluated with the novel object recognition task, and the radial water
      maze test was selected to assess rats' spatial memory. The ability of the CB1R
      antagonist, SR141716A, to counteract WIN55,212-2-induced behavioral effects was
      also tested. WIN55,212-2 (0.3, but not 0.03 or 0.1mg/kg) disrupted non
      associative learning, different aspects of short- and long-term recognition
      memory (storage and retrieval) and retention of spatial memory. The 0.3mg/kg dose
      of WIN55,212-2 also decreased ambulatory, but not vertical (rearing), activity in
      non-habituated rats. These effects appeared to be CB1R dependent since
      pretreatment with SR141716A (0.03 mg/kg) prevented the WIN55,212-2-induced
      behavioral effects. The present findings further support and extend the complex
      impact of exogenous cannabinoids on learning and memory in relation to their
      effects on locomotion.

PMID- 24867077
TI  - Restraint stress attenuates nicotine's locomotor stimulant but not discriminative
      stimulus effects in rats.
AB  - Stress enhances the locomotor stimulant and discriminative stimulus effects of
      several addictive drugs (e.g., morphine) in rodents, yet interactions between
      stress and nicotine's effects in these behavioral models have not been well
      established. To this end, the current studies examined the effects of restraint
      stress on nicotine-induced locomotor activity and nicotine discrimination in
      rats. We used a novel approach in which onset of stress and nicotine
      administration occurred concurrently (i.e., simultaneous exposure) to simulate
      effects of stress on ongoing tobacco use, as well as a more traditional approach
      in which a delay was imposed between stress and nicotine administration (i.e.,
      sequential exposure). Simultaneous exposure to stress reduced the rate of
      locomotor sensitization induced by daily injections of nicotine (0.4 mg/kg,
      s.c.). A lower dose of nicotine (0.1mg/kg, s.c.) produced modest effects on
      activity that were generally unaffected by simultaneous exposure to stress.
      Sequential exposure to stress and nicotine (0.4 mg/kg, s.c.) slightly suppressed
      nicotine-induced activity but did not influence rate of locomotor sensitization.
      Neither simultaneous nor sequential exposure to stress influenced the
      discriminative stimulus effects of nicotine (0.01-0.2mg/kg, s.c.). These data
      show that restraint stress reduces nicotine's locomotor stimulant effects,
      particularly when onset of stress and nicotine exposure occurs simultaneously,
      but does not influence nicotine discrimination. These findings contrast with the
      ability of stress to enhance the effects of other drugs in these models. This
      study also suggests that studying the influence of simultaneous stress exposure
      on drug effects may be useful for understanding the role of stress in addiction.

PMID- 24867079
TI  - Molecular characterization and expressional affirmation of the beta proteasome
      subunit cluster in rock bream immune defense.
AB  - Immunoproteasomes are primarily induced upon infection and formed by replacing
      constitutive beta subunits with inducible beta subunits which possess specific
      cleavage properties that aid in the release of peptides necessary for MHC class I
      antigen presentation. In this study, we report the molecular characterization and
      expression analysis of the inducible immunosubunits PSMB8, PSMB9, PSMB9-L, and
      PSMB10 from rock bream, Oplegnathus fasciatus. The three subunits shared common
      active site residues and were placed in close proximity to fish homologues in the
      reconstructed phylogenetic tree, in which the mammalian homologues formed
      separate clades, indicating a common ancestral origin. The rock bream
      immunosubunits possessed higher identity and similarity with the fish homologues.
      RbPSMB8, RbPSMB9, RbPSMB9-L, and RbPSMB10 were multi-exonic genes with 6, 6, 7
      and 8 exons, respectively. These four genes were constitutively expressed in all
      the examined tissues. Immunostimulants such as lipopolysaccharide and poly I:C
      induced RbPSMB8, RbPSMB9, RbPSMB9-L, and RbPSMB10 in liver and head kidney,
      suggesting their possible involvement in immune defense in rock bream. 

PMID- 24867083
TI  - China's one-child policy, a policy without a future. Pitfalls of the "common
      good" argument and the authoritarian model.
AB  - The Chinese Communist Party government has been forcefully promoting its jihua
      shengyu (planned fertility) program, known as the "one-child policy," for more
      than three decades. A distinctive authoritarian model of population governance
      has been developed. A pertinent question to be asked is whether China's one-child
      policy and the authoritarian model of population governance have a future. The
      answer must be no; they do not. Although there are many demographic, economic,
      and social rationales for terminating the one-child policy, the most fundamental
      reason for opposing its continuation is drawn from ethics. The key ethical
      rationale offered for the policy is that it promotes the common social good, not
      only for China and the Chinese people but for the whole human family. The major
      irony associated with this apparently convincing justification is that, although
      designed to improve living standards and help relieve poverty and
      underdevelopment, the one-child policy and the application of the authoritarian
      model have instead caused massive suffering to Chinese people, especially women,
      and made them victims of state violence. A lesson from China--one learned at the
      cost of individual and social suffering on an enormous scale--is that an
      essential prerequisite for the pursuit of the common good is the creation of
      adequate constraints on state power.

PMID- 24867081
TI  - Characterization of 40 single nucleotide polymorphism (SNP) via Tm-shift assay in
      the mud crab (Scylla paramamosain).
AB  - In this study, single nucleotide polymorphism (SNP) were identified, confirmed
      and genotyped in the mud crab (Scylla paramamosain) using Tm-shift assay. High
      quality sequences (13, 311 bp long) were obtained by re-sequencing that contained
      91 SNPs, with a density of one SNP every 146 bp. Of all 91 SNPs, 40 were
      successfully genotyped and characterized using 30 wild specimens by Tm-shift
      assay. The minor allele frequency per locus ranged from 0.017 to 0.500. The
      observed and expected heterozygosity, and polymorphism information content (PIC)
      ranged from 0.000 to 0.600, from 0.033 to 0.509, and from 0.033 to 0.375,
      respectively, with an average of 0.142, 0.239 and 0.198 per locus. Seventeen SNPs
      were significantly deviated from Hardy-Weinberg equilibrium. No significant
      linkage disequilibrium between pairs of loci was detected after sequential
      Bonferroni correction (P > 0.00125). Seventeen SNPs were related with known
      function genes. This study provided new molecular markers for investigation of
      population genetic diversity, construction of genetic linkage maps and molecular
      marker-assisted selection in this important crustacean species.

PMID- 24867084
TI  - The number and cycle of rat vibrissae according to topographic arrangement.
AB  - This study investigated the cycle of rat vibrissae by counting their number
      relative to their topographic arrangement. The average duration of maintaining
      single or double vibrissal shafts was analyzed. The ratio of the lifetime of the
      single and double shafts was around 3:2 weeks. The rostral and caudal vibrissae
      had relatively short and long cyclic durations, respectively; this difference may
      be related to their length and function.

PMID- 24867088
TI  - Imaging charge separation and carrier recombination in nanowire p-i-n junctions
      using ultrafast microscopy.
AB  - Silicon nanowires incorporating p-type/n-type (p-n) junctions have been
      introduced as basic building blocks for future nanoscale electronic components.
      Controlling charge flow through these doped nanostructures is central to their
      function, yet our understanding of this process is inferred from measurements
      that average over entire structures or integrate over long times. Here, we have
      used femtosecond pump-probe microscopy to directly image the dynamics of
      photogenerated charge carriers in silicon nanowires encoded with p-n junctions
      along the growth axis. Initially, motion is dictated by carrier-carrier
      interactions, resulting in diffusive spreading of the neutral electron-hole
      cloud. Charge separation occurs at longer times as the carrier distribution
      reaches the edges of the depletion region, leading to a persistent electron
      population in the n-type region. Time-resolved visualization of the carrier
      dynamics yields clear, direct information on fundamental drift, diffusion, and
      recombination processes in these systems, providing a powerful tool for
      understanding and improving materials for nanotechnology. 

PMID- 24867080
TI  - Ebselen, a promising antioxidant drug: mechanisms of action and targets of
      biological pathways.
AB  - Ebselen, an organoselenium compound, mimics glutathione peroxidase activity. It
      is a multifunctional compound, which catalyzes several essential reactions for
      the protection of cellular components from oxidative and free radical damage.
      Based on a number of in vitro and in vivo studies, various mechanisms are
      proposed to understand the biomedical actions of ebselen in health and diseases.
      It modulates metallo-proteins, enzymatic cofactors, gene expression, epigenetics,
      antioxidant defenses and immune systems. Owing to these properties, ebselen is
      currently under clinical trials for the prevention and treatment of various
      disorders such as cardiovascular diseases, arthritis, stroke, atherosclerosis,
      and cancer. A few ebselen-based pharmaceutical agents are under extensive
      investigation. As ebselen has been shown to have significant cellular toxicity,
      appropriate studies are needed to redesign the ebselen-based therapy for clinical
      trials. This review summarizes current understanding of the biochemical and
      molecular properties, and pharmacological applications of ebselen and future
      directions in this area of research.

PMID- 24867087
TI  - Penetrating stab injuries at a single urban unit: are we missing the point?
AB  - BACKGROUND: Penetrating trauma--the classical presentation of disorganised crime-
      can pose a challenge in their management due to their complexity and
      unpredictability. AIM: We examined the experience of one urban unit in the
      management of penetrating injuries to draw conclusions pertinent to other Irish
      centres. METHODS: A retrospective study was performed of all penetrating injuries
      presenting to the Emergency Department (ED) of Connolly Hospital, Dublin between
      January 2009 and December 2012. Information was collected from the Hospital
      Inpatient Enquiry database, theatre logbooks and ED records. RESULTS: One hundred
      and four patients presented with penetrating injuries in the given period. Four
      mortalities were recorded. Abdominal injury was recorded in 22% of patients; 26%
      had multiple injuries not involving the abdomen; 11% had an isolated thoracic
      injury. Fifty-seven percent required surgery, of which 40% required emergency or
      early surgical intervention. Laparotomy and laparoscopy were required in 14 and
      7%, respectively; 5% required thoracotomy of which two had penetrating cardiac
      injuries, both of whom survived. CONCLUSIONS: Although many patients with
      penetrating trauma can be safely managed conservatively, our study shows that
      over half required surgical intervention. These data highlight the need for a
      trauma team in each Irish centre receiving trauma with a clear need for general
      surgeons on emergency on-call rotas to be experienced in trauma management. There
      is an urgent need to centralise the management of trauma to a limited number of
      designated trauma centres where expertise is available by surgeons with a special
      interest in trauma management.

PMID- 24867089
TI  - Evidence-based patient decontamination: an integral component of mass exposure
      chemical incident planning and response.
AB  - Decontaminating patients who have been exposed to hazardous chemicals can
      directly benefit the patients' health by saving lives and reducing the severity
      of toxicity. While the importance of decontaminating patients to prevent the
      spread of contamination has long been recognized, its role in improving patient
      health outcomes has not been as widely appreciated. Acute chemical toxicity may
      manifest rapidly-often minutes to hours after exposure. Patient decontamination
      and emergency medical treatment must be initiated as early as possible to
      terminate further exposure and treat the effects of the dose already absorbed. In
      a mass exposure chemical incident, responders and receivers are faced with the
      challenges of determining the type of care that each patient needs (including
      medical treatment, decontamination, and behavioral health support), providing
      that care within the effective window of time, and protecting themselves from
      harm. The US Department of Health and Human Services and Department of Homeland
      Security have led the development of national planning guidance for mass patient
      decontamination in a chemical incident to help local communities meet these
      multiple, time-sensitive health demands. This report summarizes the science on
      which the guidance is based and the principles that form the core of the updated
      approach.

PMID- 24867091
TI  - Coagulation at the blood-electrode interface: the role of electrochemical
      desorption and degradation of fibrinogen.
AB  - The influence of electrochemistry on the coagulation of blood on metal surfaces
      was demonstrated several decades ago. In particular, the application of cathodic
      currents resulted in reduced surface thrombogenicity, but no molecular mechanism
      has been so far proposed to explain this observation. In this article we used for
      the first time the quartz crystal microbalance with dissipation monitoring
      technique coupled with an electrochemical setup (EQCM-D) to study thrombosis at
      the blood-electrode interface. We confirmed the reduced thrombus deposition at
      the cathode, and we subsequently studied the effect of cathodic currents on
      adsorbed fibrinogen (Fg). Using EQCM and mass spectrometry, we found that upon
      applying currents Fg desorbed from the electrode and was electrochemically
      degraded. In particular, we show that the flexible N-terminus of the alpha-chain,
      containing an important polymerization site, was cleaved from the protein, thus
      affecting its clottability. Our work proposes a molecular mechanism that at least
      partially explains how cathodic currents reduce thrombosis at the blood-electrode
      interface and is a relevant contribution to the rational development of medical
      devices with reduced thrombus formation on their surface. 

PMID- 24867090
TI  - Oligosaccharide shells as a decisive factor for moderate and strong ionic
      interactions of dendritic poly(ethylene imine) scaffolds under shear forces.
AB  - For better understanding and improving the non-covalent interactions of dendritic
      core-shell, we evaluated the interactions of hyperbranched poly(ethylene imine)
      (PEI) decorated with various oligosaccharide shells with water-soluble B
      vitamins, an estradiol derivative and pantoprazole. Depending on the different
      properties of the analyte molecules, dendritic core-shell glyco architectures
      showed (very) weak, moderate and strong interactions with the analyte molecules.
      Thus, ionic interactions are the strongest driving force for the formation of
      host-guest complexes. The core-shell glyco architecture is a necessary
      prerequisite for stable analyte/PEI complexes; the pure hyperbranched PEI did not
      show any sufficiently strong interactions with neutral, cationic or anionic
      analytes under the shear forces applied during ultrafiltration of pure aqueous
      solution without an adjusted pH. Thus, only robust non-covalent interactions
      between analytes and the dendritic polyamine scaffold of the glycopolymer
      structure survive this separation step and allow isolation of stable host-guest
      complexes in aqueous solution. 

PMID- 24867092
TI  - Isolation and structural and pharmacological characterization of alpha-elapitoxin
      Dpp2d, an amidated three finger toxin from black mamba venom.
AB  - We isolated a novel, atypical long-chain three-finger toxin (TFT), alpha
      elapitoxin-Dpp2d (alpha-EPTX-Dpp2d), from black mamba (Dendroaspis polylepis
      polylepis) venom. Proteolytic digestion with trypsin and V8 protease, together
      with MS/MS de novo sequencing, indicated that the mature toxin has an amidated C
      terminal arginine, a posttranslational modification rarely observed for snake
      TFTs. alpha-EPTX-Dpp2d was found to potently inhibit alpha7 neuronal nicotinic
      acetylcholine receptors (nAChR; IC50, 58 +/- 24 nM) and muscle-type nAChR (IC50,
      114 +/- 37 nM) but did not affect alpha3beta2 and alpha3beta4 nAChR isoforms at 1
      MUM concentrations. Competitive radioligand binding assays demonstrated that
      alpha-EPTX-Dpp2d competes with epibatidine binding to the Lymnea stagnalis
      acetylcholine-binding protein (Ls-AChBP; IC50, 4.9 +/- 2.3 nM). The activity
      profile and binding data are reminiscent of classical long-chain TFTs with a free
      carboxyl termini, suggesting that amidation does not significantly affect toxin
      selectivity. The crystal structure of alpha-EPTX-Dpp2d was determined at 1.7 A
      resolution and displayed a dimeric toxin assembly with each monomer positioned in
      an antiparallel orientation. The dimeric structure is stabilized by extensive
      intermolecular hydrogen bonds and electrostatic interactions, which raised the
      possibility that the toxin may exist as a noncovalent homodimer in solution.
      However, chemical cross-linking and size-exclusion chromatography coupled with
      multiangle laser light scattering (MALLS) data indicated that the toxin is
      predominantly monomeric under physiological conditions. Because of its high
      potency and selectivity, we expect this toxin to be a valuable pharmacological
      tool for studying the structure and function of nAChRs.

PMID- 24867093
TI  - Bone-marrow mesenchymal stem cell transplantation to treat diabetic nephropathy
      in tree shrews.
AB  - Diabetic nephropathy (DN) is a common microvascular complication of diabetes. We
      used a new DN model in tree shrews to validate the use of bone-marrow mesenchymal
      stem cell (BM-MSC) transplantation to treat DN. The DN tree shrew model was
      established by a high-sugar and high-fat diet and four injections of
      streptozotocin. 4',6-Diamidino-2-phenylindole labelled BM-MSCs were injected into
      tree shrews. The DN tree shrew model was successfully established. Blood glucose
      was significantly increased ( p < 0.01) during the entire experiment. DN tree
      shrews showed dyslipidemia, insulin resistance and increased 24-h proteinuria. At
      21 days after BM-MSC transplantation, glucose and levels of triglycerides, total
      cholesterol and 24-h urine volume were lower than in tree shrews with DN alone (
      p < 0.01) but were still higher than control values ( p < 0.01). Levels of
      creatinine and urea nitrogen as well as 24-h proteinuria were lower for DN tree
      shrews with BM-MSCs transplantation than DN alone ( p < 0.05). High-sugar and
      high-fat diet combined with STZ injection can induce a tree shrew model of DN. BM
      MSCs injection can home to damaged kidneys and pancreas, for reduced 24-h
      proteinuria and improved insulin resistance.

PMID- 24867094
TI  - Crebanine, an aporphine alkaloid, sensitizes TNF-alpha-induced apoptosis and
      suppressed invasion of human lung adenocarcinoma cells A549 by blocking NF-kappaB
      regulated gene products.
AB  - Crebanine is an alkaloid known to exhibit anticancer, but its mechanism is not
      well understood. Besides, the nuclear factor-kappa B (NF-kappaB) transcription
      factor has been correlated with inflammation, carcinogenesis, tumor cell
      survival, invasion, and angiogenesis. In this study, we investigated the effects
      of crebanine on tumor necrosis factor alpha (TNF-alpha)-induced NF-kappaB
      activation and the expression of NF-kappaB-regulated gene products. We found that
      crebanine reduced the cell proliferation of lung, ovarian, and breast cancer
      cells. Crebanine also potentiated TNF-alpha-induced apoptosis which correlated
      with the suppression of the gene products linked to cell survival, B cell
      lymphoma-extra large, and proliferation, cyclin D1. In addition, crebanine
      affected TNF-alpha-induced activation of caspase-8, caspase-3, and poly(ADP
      ribose) polymerase cleavage, indicating that the apoptotic effects of TNF-alpha
      were enhanced by crebanine. Moreover, crebanine reduced TNF-alpha-induced A549
      cell invasion and migration. Furthermore, crebanine suppressed the TNF-alpha
      mediated expression of proteins that involved cancer cell invasion (matrix
      metalloproteinase 9 urokinase-type plasminogen activator, urokinase-type
      plasminogen activator receptor and intercellular adhesion molecule 1) and
      angiogenesis (COX-2 and VEGF), all of which are known to be regulated by NF
      kappaB. We also demonstrated that TNF-alpha induced NF-kappaB DNA-binding
      activity, which was inhibited by crebanine. Moreover, crebanine suppressed the
      TNF-alpha-induced degradation of inhibitor of NF-kappaB alpha (IkappaBa), which
      led to reduced NF-kappaB translocation to the nucleus. Taken together, our
      results demonstrated that crebanine reduced TNF-alpha-induced cancer cell
      proliferation, invasion, and survival by suppressing NF-kappaB activity and
      expression profile of its downstream genes.

PMID- 24867095
TI  - Loss of E-cadherin promotes migration and invasion of cholangiocarcinoma cells
      and serves as a potential marker of metastasis.
AB  - Tumor progression is characterized by loss of cell adhesion and increase of
      invasion and metastasis. E-cadherin, a cell adhesion molecule, is frequently
      downregulated and has been proposed as an important mediator in epithelial
      mesenchymal transition (EMT) in tumors. In this study, we investigated the
      expression of E-cadherin and its association with cancer invasion and prognosis
      in cholangiocarcinoma (CCA). Immunohistochemistry results demonstrated a
      statistically significant association between the positive metastasis status with
      low E-cadherin protein expression in human CCA tissues (P = 0.04). Statistical
      trends were identified for low E-cadherin level and shorter survival time (P =
      0.08). Targeting the E-cadherin expression in CCA cells with siRNA caused
      upregulation of vimentin, a mesenchymal marker, and disappearance of the E
      cadherin/beta-catenin adhesion complex from cell membranes. Moreover, migration
      and invasion abilities of the cells were increased under this condition. These
      findings suggest that reduction of E-cadherin contributes to CCA progression by
      attenuating the strength of cellular adhesion, which affects motility as well as
      regulating the expression of EMT-related genes during CCA invasion and
      metastasis. Thus, E-cadherin can act as a central modulator of tumor cell
      phenotype and is a potential metastasis marker in CCA.

PMID- 24867097
TI  - High expression of Golgi phosphoprotein-3 is associated with poor survival in
      patients with hepatocellular carcinoma.
AB  - Golgi phosphoprotein 3 (GOLPH3) is recently demonstrated to function as an
      oncogene involved in the development and progression of cancers. However, little
      is known about GOLPH3 expression and its clinical significance in hepatocellular
      carcinoma (HCC). The levels of GOLPH3 messenger RNA (mRNA) and protein in HCC
      cell lines and fresh tissues were determined by quantitative RT-PCR and western
      blotting. Additionally, the protein expression of GOLPH3 was detected in 167
      paraffin-embedded HCC samples by immunohistochemistry. GOLPH3 mRNA and protein
      was overexpressed in HCC cell lines and tissues than the immortalized normal
      hepatocyte cell line LO2 and the adjacent nontumorous live tissues, respectively.
      High GOLPH3 expression was positively correlated with high serum AFP level (P =
      0.015) and more tumor recurrence or metastasis (P = 0.010). In addition, HCC
      patients with high GOLPH3 expression had poorer overall survival (hazard ratio
      (HR), 1.87; 95 % confidence interval (CI), 1.19-2.94; P = 0.006) and poorer
      disease-free survival (HR, 1.90; 95 % CI, 1.21-2.98; P = 0.005) than those with
      low GOLPH3 expression. The cumulative 5-year survival rate was only 35.19 % (95 %
      CI, 26.18-44.20 %) in the high GOLPH3 expression group, whereas it was 55.93 %
      (95 % CI, 43.26-68.60 %) in the low GOLPH3 expression group. Furthermore,
      multivariate Cox regression analysis demonstrated that the expression of GOLPH3,
      tumor size, and tumor multiplicity were independent prognostic predictors for HCC
      patients. GOLPH3 was overexpressed in HCC at both the mRNA and protein levels,
      and high expression of GOLPH3 could be served as a novel and potential prognostic
      biomarker for HCC patients.

PMID- 24867096
TI  - FBXL5 targets cortactin for ubiquitination-mediated destruction to regulate
      gastric cancer cell migration.
AB  - Cortactin, an actin-interacting protein, is implicated in cytoskeletal
      architecture and often amplified in several types of cancer including gastric
      adenocarcinomas. Downregulation of cortactin decreases cell migration and
      invasion. However, how to regulate cortactin in gastric cancer remains largely
      unknown. Here, we report that FBXL5 interacts with and targets cortactin for
      ubiquitylation and subsequent proteasomal degradation. Furthermore, we showed
      that FBXL5-induced cortactin degradation is mediated by extracellular regulated
      signal kinase (ERK). Serine phosphorylation sites mutant, cortactinS405A/S418A,
      prevent FBXL5-induced cortactin degradation. Moreover, CortactinS405A/S418A
      exhibited stronger effects in promoting gastric cancer cell migration when
      compared to wild-type cortactin. Taken together, our data suggested a novel
      molecular mechanism for the negative regulation of cortactin by FBXL5 in gastric
      cancer cells migration.

PMID- 24867098
TI  - PP121, a dual inhibitor of tyrosine and phosphoinositide kinases, inhibits
      anaplastic thyroid carcinoma cell proliferation and migration.
AB  - The tyrosine and phosphoinositide kinases play crucial roles in the regulation of
      many cancer cell processes including cell survival and cell motility. Anaplastic
      thyroid carcinoma (ATC) is a rare and deadly type of thyroid cancer, and so far,
      there are no effective therapeutic compounds for ATC. Herein, we investigate the
      anticancer activities of PP121, a dual inhibitor of tyrosine and phosphoinositide
      kinases, in ATC therapy. We found that PP121 is effective at suppressing cell
      viability, inducing cell apoptosis, and inhibiting cell migration and invasion.
      The potential anticancer mechanism for PP121 might be its inhibitory effects on
      phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathways in ATC cells.
      Furthermore, PP121 is effective at suppressing ATC tumor growth in vivo. In
      summary, our studies suggest that PP121 might be a promising therapeutic compound
      for ATC treatment, which might shed new light on ATC therapy.

PMID- 24867099
TI  - Release modeling and comparison of nanoarchaeosomal, nanoliposomal and pegylated
      nanoliposomal carriers for paclitaxel.
AB  - Breast cancer is the most prevalent cancer among women. Recently, delivering by
      nanocarriers has resulted in a remarkable evolution in treatment of numerous
      cancers. Lipid nanocarriers are important ones while liposomes and archaeosomes
      are common lipid nanocarriers. In this work, paclitaxel was used and
      characterized in nanoliposomal and nanoarchaeosomal form to improve efficiency.
      To increase stability, efficiency and solubility, polyethylene glycol 2000 (PEG
      2000) was added to some samples. MTT assay confirmed effectiveness of
      nanocarriers on MCF-7 cell line and size measuring validated nano-scale of
      particles. Nanoarchaeosomal carriers demonstrated highest encapsulation
      efficiency and lowest release rate. On the other hand, pegylated nanoliposomal
      carrier showed higher loading efficiency and less release compared with
      nanoliposomal carrier which verifies effect of PEG on improvement of stability
      and efficiency. Additionally, release pattern was modeled using artificial neural
      network (ANN) and genetic algorithm (GA). Using ANN modeling for release
      prediction, resulted in R values of 0.976, 0.989 and 0.999 for nanoliposomal,
      pegylated nanoliposomal and nanoarchaeosomal paclitaxel and GA modeling led to
      values of 0.954, 0.951 and 0.976, respectively. ANN modeling was more successful
      in predicting release compared with the GA strategy.

PMID- 24867100
TI  - MiRNA-181c inhibits EGFR-signaling-dependent MMP9 activation via suppressing Akt
      phosphorylation in glioblastoma.
AB  - As the most aggressive malignant primary human brain tumor, glioblastoma is noted
      with extremely poor patient survival. Previous studies have demonstrated that
      expression of matrix metalloproteinase-9 (MMP9) in glioblastoma cells is critical
      for cancer metastasis. However, the molecular signaling pathways that control
      MMP9 activation remain undefined. Here, we reported a strong negative correlation
      of microRNA (miRNA)-181c levels with either MMP9 levels or activation of
      epidermal growth factor receptor (EGFR) signaling in glioblastoma patients. EGF
      induced activation of EGFR in a human glioblastoma line, A-172 cells, increased
      MMP9 expression through activation of phosphatidylinositol 3-kinase (PI3K)/Akt
      pathway, without affecting expression of miRNA-181c. On the other hand,
      overexpression of miRNA-181c in A-172 cells inhibited MMP9 expression by
      inhibiting Akt phosphorylation, but not phosphorylation of EGFR receptor. Taken
      together, these findings suggest that EGFR signaling activates downstream
      PI3K/Akt to increase MMP9 expression in glioblastoma, while phosphorylation of
      Akt is a control point by miRNA-181c. Our work thus provides new insights into
      the molecular basis underlying the metastasis of glioblastoma.

PMID- 24867102
TI  - Hemolysis in a laminar flow-through Couette shearing device: an experimental
      study.
AB  - Reducing hemolysis has been one of the major goals of rotary blood pump
      development and in the investigational phase, the capability of hemolysis
      estimation for areas of elevated shear stresses is valuable. The degree of
      hemolysis is determined by the amplitude of shear stress and the exposure time,
      but to date, the exact hemolytic behavior at elevated shear stresses and
      potential thresholds for subcritical shear exposure remain vague. This study
      provides experimental hemolysis data for a set of shear stresses and exposure
      times to allow better estimations of hemolysis for blood exposed to elevated
      shearing. Heparinized porcine blood with a hematocrit of 40% was mechanically
      damaged in a flow-through laminar Couette shear flow at a temperature of 23
      degrees C. Four levels of shear stress, 24, 592, 702, and 842 Pa, were replicated
      at two exposure times, 54 and 873 ms. For the calculation of the shear stresses,
      an apparent viscosity of 5 mPas was used, which was verified in an additional
      measurement of the blood viscosity. The hemolysis measurements were repeated four
      times, whereby all conditions were measured once within the same day and with
      blood from the same source. Samples were taken at the inlet and outlet of the
      shear region and an increase in plasma-free hemoglobin was measured. An index of
      hemolysis (IH) was thereby calculated giving the ratio of free to total
      hemoglobin. The results are compared with data from previously published studies
      using a similar shearing device. Hemolysis was found to increase exponentially
      with shear stress, but high standard deviations existed at measurements with
      elevated IH. At short exposure times, the IH remained low at under 0.5% for all
      shear stress levels. For high exposure times, the IH increased from 0.84% at 592
      Pa up to 3.57% at the highest shear stress level. Hemolysis was significant for
      shear stresses above ~600 Pa at the high exposure time of 873 ms.

PMID- 24867101
TI  - Nrdp1 inhibits growth of colorectal cancer cells by nuclear retention of p27.
AB  - The molecular mechanism underlying the proliferation of colorectal cancer (CRC)
      cells is not completely understood. Here, we found that the level of neuregulin
      receptor degradation protein-1 (Nrdp1) E3 ubiquitin ligase was significantly
      decreased in CRC tissues, compared with the adjacent normal tissues from human
      patients. Knockdown of Nrdp1 enhanced the proliferation of CRC cells, while
      overexpression of Nrdp1 inhibited the proliferation of CRC cells. Further
      analysis showed that Nrdp1 may induce degradation of its target ErbB3 to inhibit
      activation of both ERK/MAPK and PI3K/Akt pathways in CRC cells, which seemed to
      affect cell proliferation via nuclear retention of a major cell-cycle inhibitor,
      p27. Taken together, these findings suggest that Nrdp1-mediated ErbB3 degradation
      suppresses cellular growth of CRC and that Nrdp1 loss in CRC may promote tumor
      progression, thus highlighting Nrdp1 as a novel target for CRC therapy.

PMID- 24867103
TI  - The cyanate and 2-phosphaethynolate anion congeners ECO- (E = N, P, As, Sb, Bi):
      prelude to experimental characterization.
AB  - Pioneering synthetic research by the groups of Grutzmacher and Goicoechea have
      made possible the preparation of 2-phosphaethynolates (PCO(-)). The obvious
      question arises: can progress be made toward AsCO(-), SbCO(-), and BiCO(-)? Here
      the properties of all five anion congeners ECO(-) (E = N, P, As, Sb, Bi) were
      systematically investigated using ab initio coupled-cluster methods with
      correlation-consistent basis sets cc-pVXZ (X = D, T, Q). These anions exhibit
      linear structures with significant natural bond orbital negative charge on both
      the E and O atoms. These species should react with electrophiles via attack at
      either center. On going from nitrogen to bismuth, with the atomic radius
      increasing, the bond between E and C becomes weaker, while the C-O bond tends to
      be slightly stronger. By the time one gets to BiCO(-), the C-O bond distance is
      1.181 A, indicating a very strong double bond. Relative to the PCO(-) anion,
      which is reactive toward several unsaturated compounds, the As/Sb/BiCO(-) anions
      may undergo cycloaddition more readily with unsaturated substrates. The
      dissociation energy of the E-C bond, except for that of NCO(-), is predicted to
      be much less than that of the C-O bond. These dissociation energies are 76
      kcal/mol (P(-)-CO), 58 kcal/mol (As(-)-CO), 37 kcal/mol (Sb(-)-CO), and 28
      kcal/mol (Bi(-)-CO). Even the BiCO(-) anion should be achievable in the
      laboratory. The vibrational frequencies for these anions are predicted, and our
      results should assist in the experimental characterization and exploration of the
      heavier congeners ECO(-). 

PMID- 24867104
TI  - Hybrid superconducting-magnetic memory device using competing order parameters.
AB  - In a hybrid superconducting-magnetic device, two order parameters compete, with
      one type of order suppressing the other. Recent interest in ultra-low-power, high
      density cryogenic memories has spurred new efforts to simultaneously exploit
      superconducting and magnetic properties so as to create novel switching elements
      having these two competing orders. Here we describe a reconfigurable two-layer
      magnetic spin valve integrated within a Josephson junction. Our measurements
      separate the suppression in the superconducting coupling due to the exchange
      field in the magnetic layers, which causes depairing of the supercurrent, from
      the suppression due to the stray magnetic field. The exchange field suppression
      of the superconducting order parameter is a tunable and switchable behaviour that
      is also scalable to nanometer device dimensions. These devices demonstrate non
      volatile, size-independent switching of Josephson coupling, in magnitude as well
      as phase, and they may enable practical nanoscale superconducting memory devices.

PMID- 24867105
TI  - Regulatory requirements: a necessary evil or a way to highlight the essence of
      good nursing care?

PMID- 24867106
TI  - Fostering hope in the patient with cancer.
AB  - When a patient is diagnosed with cancer, feelings such as fear, anxiety, and
      hopelessness can negatively affect a person's frame of mind. Hope can help a
      patient decrease anxiety and increase quality of life. Nurses should assess hope,
      provide interventions, be empathetic, listen, and treat patients with dignity to
      help improve hope and quality of life. This article features how hope can have a
      positive impact and provides specific information about how nurses can promote
      and foster hope in patients with cancer.

PMID- 24867107
TI  - Highly reliable health care in the context of oncology nursing: Part II.
AB  - The principles of reliability science are used in various high-risk and high-tech
      industries to improve quality and safety. In part one of this two-part series,
      three of the five principles (the principles of anticipation) were discussed as
      they pertain to delivering oncology care in challenging and variable
      circumstances. This article will address the final two principles (the principles
      of containment) and examine how a healthcare organization responds when an error
      in treatment has occurred. 

PMID- 24867108
TI  - Evidence-based management of sepsis.
AB  - Sepsis is a potential life-threatening oncologic emergency. Early recognition and
      prompt intervention can decrease the morbidity and mortality associated with
      sepsis. The Surviving Sepsis Campaign Guidelines Committee updated its
      recommendations in 2012, outlining specific evidence-based interventions to
      manage sepsis.

PMID- 24867110
TI  - Using failure-to-rescue simulation to assess the performance of advanced practice
      professionals.
AB  - The use of advanced practice professionals (APPs) has been established in
      oncology care. APPs are frequently the most readily available ordering provider
      for care guidance when it becomes evident that a patient with cancer is failing.
      The purpose of the current preliminary descriptive project was to determine the
      best method for assessing APP performance in oncology-specific circumstances,
      particularly in the failing patient with cancer. A test group of 14 APPs
      completed a competency self-assessment, the Basic Knowledge Assessment Tool
      (BKAT)-8SR, and attended a four-hour simulation and classroom experience.
      Competency checklists with 30 priority interventions for each scenario had been
      anticipated by an expert panel. The APP competency self-assessment was measured
      for knowledge base and critical thinking. All of the APPs scored at or above the
      level of a critical care nurse with one year of experience on the BKAT-8SR.
      Twenty-seven of the anticipated interventions were enacted by all APPs. Five
      additional interventions were ordered that had not been anticipated. The success
      of this educational strategy has stimulated new learning opportunities, including
      initiation of a full-team oncology failure-to-rescue simulation, course
      restructuring, and other innovative simulation experiences.

PMID- 24867109
TI  - Safe management of chemotherapy: infusion-related complications.
AB  - The following is a reprint from Chapter 8 in Chemotherapy and Biotherapy
      Guidelines and Recommendations for Practice (Fourth Edition) by Martha Polovich,
      PhD, RN, AOCN(r), MiKaela Olsen, MS, RN, AOCNS(r), and Kristine B. LeFebvre, MSN,
      RN, AOCN(r) (Eds.).

PMID- 24867111
TI  - Primer on immuno-oncology and immune response.
AB  - Advances in the understanding of the immunogenicity of tumors have provided the
      basis for immuno-oncology, the development of immunotherapeutic agents that
      augment the patient's antitumor immunity and disrupt the immune-regulatory
      circuits that allow tumors to evade the immune system. Two immunomodulatory
      agents recently have been introduced for the treatment of malignancy: sipuleucel
      T and ipilimumab. Unlike cytotoxic chemotherapy, immunotherapies stimulate the
      patient's immune system to mount or augment existing endogenous antitumor immune
      responses. Both agents have demonstrated significant improvements in long-term
      overall survival in patients. Like other immunotherapies, sipuleucel-T and
      ipilimumab also are characterized by adverse events that manifest as immune
      related inflammatory conditions that typically are low grade. Management
      guidelines have been developed and emphasize early recognition of the signs and
      symptoms of immune-related adverse events and treatment with corticosteroids.
      Because these events can manifest even after the cessation of therapy, patients
      treated with immunotherapies should continue to be followed by their oncology
      team and other healthcare providers.

PMID- 24867112
TI  - Standardizing central venous catheter care by using observations from patients
      with cancer.
AB  - To understand the vulnerability of patients with cancer to central line
      associated bloodstream infections related to tunneled central venous catheters
      (CVCs), patients were asked to describe their line care at home and in clinic and
      to characterize their knowledge and experience managing CVCs. Forty-five adult
      patients with cancer were recruited to participate. Patients were interviewed
      about the type of line, duration of use, and observations of variations in line
      care. They also were asked about differences between line care at home and in the
      clinic, precautions taken when bathing, and their education regarding line care.
      Demographic information and primary cancer diagnosis were taken from the
      patients' medical records. Patients with hematologic and gastrointestinal
      malignancies were heavily represented. The majority had tunneled catheters with
      subcutaneous implanted ports. Participants identified variations in practice
      among nurses who cared for them. Although many participants expressed confidence
      in their knowledge of line care, some were uncertain about what to do if the
      dressing became loose or wet, or how to recognize an infection. Patients seemed
      to be astute observers of their own care and offered insights into practice
      variation. Their observations show that CVC care practices should be
      standardized, and educational interventions should be created to address
      patients' knowledge deficits.

PMID- 24867113
TI  - Optimizing the management of patients with myelofibrosis.
AB  - Myelofibrosis (MF) is a rare myeloproliferative neoplasm of the bone marrow
      associated with shortened survival. The disease is characterized by splenomegaly,
      cytopenias, and multiple disease-related symptoms that reduce quality of life.
      The clinical management of MF can be challenging because of its heterogeneous
      presentation and disease course. Therefore, knowledge of the underlying pathology
      and clinical manifestations of MF is needed. Ruxolitinib, a Janus kinase (JAK) 1
      and 2 inhibitor, is the first therapy to be approved by the U.S. Food and Drug
      Administration for intermediate- or high-risk MF. Ruxolitinib therapy offers
      advantages over the previous palliative treatments and has shown durable
      reductions in splenomegaly and disease symptoms as well as improvements in
      quality of life. Two-year follow-up of the phase III trials also has shown that
      ruxolitinib treatment was associated with a survival advantage relative to
      control groups. Dose-dependent thrombocytopenia and anemia are expected but
      manageable adverse effects caused by the targeted JAK inhibition of ruxolitinib.
      This review provides an overview of MF and assessment of the primary clinical
      disease manifestations, with a focus on ruxolitinib from the oncology nurse
      perspective.

PMID- 24867114
TI  - Lung cancer screening guidelines. The nurse's role in patient education and
      advocacy.
AB  - Although the third leading cancer in incidence following breast and prostate,
      lung cancer is the principal cause of cancer death in the United States. The
      majority of lung cancer cases are detected at an advanced stage when surgical
      resection is no longer an option. Recent research has concluded that lung cancer
      screening with low-dose computed tomography for specific high-risk groups may
      reduce lung cancer mortality. Public awareness and the need for current
      information are growing regarding the state of the science relative to lung
      cancer screening for individuals at high risk for lung cancer. This article
      provides a historical perspective on the topic of lung cancer screening. The
      risks and benefits of screening are discussed, and current clinical practice
      guidelines are reviewed. Oncology nurses will need to be cognizant of the risks,
      benefits, and current guidelines related to lung cancer screening as they support
      patients and their families making informed decisions about personal health care.

PMID- 24867116
TI  - Engraftment syndrome in hematopoietic stem cell transplantations.
AB  - Hematopoietic stem cell transplantation (HSCT) is an increasingly common
      treatment option for malignant and nonmalignant diseases, but it has significant
      associated morbidity and mortality. Nurses caring for HSCT recipients must be
      aware of all potential complications, including engraftment syndrome (ES).
      Previous nursing literature has included little information on this syndrome,
      which often presents with noninfectious fever, skin rash, and pulmonary
      infiltrates, and ES may be fatal if left unidentified and treatment is not
      initiated promptly. Reports of the risk factors, incidence, clinical
      manifestations, diagnosis, treatment, and outcomes have much variation, likely
      from a lack of definite diagnostic criteria and inconsistency in the terminology
      associated with ES. The purpose of this article is to provide an overview of ES
      and the implications for nursing practice and research.

PMID- 24867115
TI  - Development of a patient education resource for women with gynecologic cancers:
      cancer treatment and sexual health.
AB  - The diagnosis of gynecologic cancer has a dramatic impact on the emotional,
      social, and sexual domains of a woman's life. The complexities of human sexuality
      are broad, particularly for people coping with life-threatening illness. Healthy
      sexual expression can affirm love, relieve stress and anxiety, foster hope,
      accentuate spirituality, and distract one from the emotional and physical
      sequelae of chronic illness. This article reports on the development of a sexual
      health education guide for women diagnosed with ovarian cancer who experienced a
      recurrence and were undergoing treatment. Extensive literature and the findings
      of this study document that patients often feel that sexuality has been ignored
      in their cancer care. This article provides examples of the responses from study
      participants and the resulting integration of those responses into the guide.

PMID- 24867117
TI  - Cancer genetics and genomics: essentials for oncology nurses.
AB  - Cancer genetics and genomics are rapidly evolving, with new discoveries emerging
      in genetic mutations, variants, genomic sequencing, risk-reduction methods, and
      targeted therapies. To educate patients and families, state-of-the-art care
      requires nurses to understand terminology, scientific and technological advances,
      and pharmacogenomics. Clinical application of cancer genetics and genomics
      involves working in interdisciplinary teams to properly identify patient risk
      through assessing family history, facilitating genetic testing and counseling
      services, applying risk-reduction methods, and administering and monitoring
      targeted therapies.

PMID- 24867118
TI  - The need for routine monitoring of cardiac function in patients receiving 5
      fluorouracil infusion.
AB  - Fluorouracil (5-FU) is an antimetabolite that has become the cornerstone
      chemotherapeutic agent used to treat tumors of the gastrointestinal tract.
      Although proven to be effective, 5-FU can cause cardiotoxicity, which can be life
      threatening. Adverse cardiac-related events induced by 5-FU include angina
      pectoris, myocardial infarction, supraventricular tachycardia, and atrial
      fibrillation. Nurses play a crucial role in the routine monitoring of cardiac
      function by identifying patients at high risk of developing 5-FU-related
      cardiotoxicity, monitoring patients during treatment, and then implementing
      specific interventions if 5-FU-related cardiotoxicity is identified or suspected.
      This article discusses the relevance of 5-FU-related cardiotoxicity, highlights
      the need for routine monitoring of cardiac function, and discusses methods of
      early detection and management. 

PMID- 24867119
TI  - Oncology nurses and indoor tanning: stylish or risky behavior?
AB  - Being tan has become a social norm, and some nurses engage in that widely
      accepted lifestyle. Mounting evidence of the increased risk to melanoma and
      nonmelanoma skin cancers associated with indoor tanning supports the need for
      nurses to integrate skin cancer education, counseling, and referrals into routine
      practice. The current article presents an overview of the risks associated with
      indoor tanning, discusses its acceptance as a social norm, and offers strategies
      to support oncology nurses in changing the widespread trend.

PMID- 24867120
TI  - Influenza vaccines in immunosuppressed adults with cancer.

PMID- 24867121
TI  - A telling transition: new graduate nursing in the oncology and bone marrow
      transplantation setting.
AB  - The University of Colorado Hospital's Post-Baccalaureate Nurse Residency Program
      is a Commission on Collegiate Nursing Education-accredited program structured to
      provide critical elements important for a successful transition into professional
      nursing practice. As part of the program, graduate nurse residents receive a year
      of education that includes 12-24 weeks of precepted orientation on the clinical
      unit, paid specialty courses, and monthly seminars that provide additional
      curriculum and mentoring support. At the completion of the program, the residents
      complete an evidence-based practice project and a clinical narrative summarizing
      their residency experience. The following is an example of one resident's
      exemplar.

PMID- 24867122
TI  - Predicting radiotherapy-related clinical toxicities in cancer: a literature
      review.
AB  - Assessment of patients receiving radiotherapy for cancer is essential, with the
      ability to identify those who may be more likely to experience radiotherapy
      related side effects noted as an important issue for nurses. Body mass, age, and
      radiation dose may be predictive factors for the development of such side
      effects. This review considers these factors and how nurses can use this evidence
      to inform their care, with results indicating that the dose of radiation, the
      site treated, and body mass index are predictive of toxicities that may develop.
      Increased awareness of these predictive factors will aid nurses in identifying
      patients at greater risk of developing radiation-related side effects. This will
      assist in guiding nursing interventions, as well as enabling the
      individualization of patient education, by placing greater emphasis on preventive
      measures for patients who are more vulnerable to the development of radiation
      related toxicities.

PMID- 24867123
TI  - The effects of music on pain and anxiety during screening mammography.
AB  - One in four women who are diagnosed with breast cancer die annually, and the
      single most important way to prevent this is early detection; therefore, women
      older than 40 years should have an annual screening mammography. Many barriers
      have been reported that prevent compliance with this recommendation, including
      lack of insurance, fear, anxiety, pain, worry, and mistrust of the medical
      community. Nurses are in a position to use creative interventions, such as music
      therapy, to help minimize barriers. Although this study did not show that music
      therapy during screening mammograms decreased the amount of pain that the
      participants experienced, it did suggest that music therapy has the potential to
      decrease the amount of anxiety. Assisting patients in decreasing anxiety reduces
      barriers for screening mammography. The literature does suggest that music is a
      distraction for many populations of patients; however, when patients are faced
      with the possible diagnosis of breast cancer, it may be difficult to find an
      intervention to distract a woman's mind, which was supported by the findings of
      this study.

PMID- 24867124
TI  - Reasons for nonadherence to tamoxifen and aromatase inhibitors for the treatment
      of breast cancer: a literature review.
AB  - Despite improved breast cancer survival rates with the use of tamoxifen and
      aromatase inhibitors, patients remain at risk for cancer recurrence and mortality
      because of nonadherence to medication. The objective of this review was to
      identify factors associated with nonadherence among patients with breast cancer.
      Electronic databases were searched for studies, and potentially relevant studies
      were retrieved and assessed for eligibility. Potential factors associated with
      nonadherence were identified, and they included patient-related factors (e.g.,
      patient beliefs and knowledge, fear of adverse effects, forgetfulness, smoking,
      age, race), therapy-related factors (e.g., duration, side effects, additional
      prescribed medications, treatment interfering with lifestyle), healthcare system
      factors (e.g., patient/provider relationships), socioeconomic factors (e.g.,
      medication costs, burden, scheduling problems, religion, marital status), and
      disease-related factors (e.g., comorbidities, stage of breast cancer). Those
      findings highlight the need for development of interventions to promote long-term
      adherence in patients with breast cancer.

PMID- 24867125
TI  - Decision making after BRCA genetic testing. Down the road of transition.
AB  - The purpose of this study was to evaluate women who have completed hereditary
      cancer risk assessment and BRCA genetic testing to determine if they considered
      themselves prepared to proceed with decision making regarding cancer screening
      and prevention options. Levels of decisional conflict were explored, as was their
      preference for information delivery. The prospective, descriptive survey was
      conducted at a breast and clinical genetics clinic at a comprehensive cancer
      center in the northeastern United States. Twenty-seven female participants
      completed the Preparation for Decision Making scale, Decisional Conflict Scale,
      and a demographic questionnaire. Scores were consistent with high levels of
      preparation for decision making and low decisional conflict. The face-to-face
      approach was the preferred method for information delivery. Subgroup analysis
      demonstrated a difference in the measured objectives based on cancer status but
      not based on BRCA status. The current information delivery approach is meeting
      the decision-making needs of women considered to be at increased risk for
      hereditary breast and ovarian cancer.

PMID- 24867126
TI  - Biosynthetic code for divergolide assembly in a bacterial mangrove endophyte.
AB  - Divergolides are structurally diverse ansamycins produced by a bacterial
      endophyte (Streptomyces sp.) of the mangrove tree Bruguiera gymnorrhiza. By
      genomic analyses a gene locus coding for the divergolide pathway was detected.
      The div gene cluster encodes genes for the biosynthesis of 3-amino-5
      hydroxybenzoate and the rare extender units ethylmalonyl-CoA and isobutylmalonyl
      CoA, polyketide assembly by a modular type I polyketide synthase (PKS), and
      enzymes involved in tailoring reactions, such as a Baeyer-Villiger oxygenase. A
      detailed PKS domain analysis confirmed the stereochemical integrity of the
      divergolides and provided valuable new insights into the formation of the diverse
      aromatic chromophores. The bioinformatic analyses and the isolation and full
      structural elucidation of four new divergolide congeners led to a revised
      biosynthetic model that illustrates the formation of four different types of
      ansamycin chromophores from a single polyketide precursor.

PMID- 24867127
TI  - A structural analysis of N-glycans of neonatal porcine islet-like cell clusters
      (NPCC).
AB  - BACKGROUND: N-glycans isolated from neonatal porcine islet-like cell clusters
      (NPCCs) were analyzed by a mapping technique, to examine the differences in
      glycosylation and antigenicity between adult pig islets (APIs) and NPCCs.
      METHODS: NPCCs were isolated from 1-to-3 day-old neonatal wild-type pigs and
      cultured for 9 days, using the technique described by Korbutt et al. The extract
      was proteolyzed by treatment with a chymotrypsin and trypsin mixture and further
      digested with glycoamidase A to release the N-glycans. After the removal of the
      peptide materials, the reducing ends of the N-glycans were derivatized with 2
      aminopyridine. This mixture was applied to DEAE, amide and ODS columns. PA
      oligosaccharides were also subjected to MALDI TOF-MS analysis. RESULTS: The NPCC
      glycans were comprised of 14 neutral, 5 mono-sialyl and 5 di-sialyl glycans. As a
      feature of the N-glycans of NPCC, NPCC contained large amounts of high mannose
      structures. On the other hand, all of the hybrid and complex types contained a
      Fucalpha1-6GlcNAc structure, but were not modified with sulfate residues. Among
      them, the NPCC preparation contained five neutral and two mono-sialyl glycans and
      two di-sialyl glycans that were not typically found in adult islets, and seven of
      these nine were not detected in human islets. Moreover, most of the structures
      could be clearly identified in this study. CONCLUSIONS: The data herein will be
      helpful for future studies of the glycoantigen associated with NPCC.

PMID- 24867128
TI  - Pediatric dural arteriovenous malformations.
AB  - Pediatric dural arteriovenous malformations (dAVMs) are rare lesions that have a
      high mortality rate and require complex management. The authors report 3 cases of
      pediatric dAVMs that presented with macrocrania and extracranial venous
      distension. Dural sinus thrombosis developed in 2 of the cases prior to any
      intervention, which is an unusual occurrence for this particular disease. All 3
      cases were treated using staged endovascular embolization with a favorable
      outcome in 1 case and a poor outcome in the other 2 cases. Complications
      developed in all cases and included dural sinus thrombosis, parenchymal
      hemorrhage, intracranial venous hypertension, and seizures. The strategies and
      challenges used in managing these patients will be presented and discussed, along
      with a review of the literature. While outcomes remain poor, the authors conclude
      that prompt treatment with endovascular embolization provides the best results
      for children with these lesions. A well-established venous collateral circulation
      draining directly to the internal jugular veins may further improve the rate of
      favorable outcome after embolization. 

PMID- 24867129
TI  - Social engagement, setting and alcohol use among a sample of older Australians.
AB  - The harms associated with risky alcohol consumption have long been researched and
      recognised in the health field. However, little available research has focused on
      older people or extended analysis of alcohol use by this segment of the
      population beyond a biomedical perspective. With the rapid ageing of the global
      population, research that investigates alcohol use among older people from a
      social perspective is important. This article reports on research with a group of
      older women and men, to identify and explain factors that influence alcohol
      consumption. In-depth interviews were conducted in Perth, Western Australia with
      20 men and 22 women aged 65-74 years who were living in either private residences
      or retirement villages. The study findings indicated that alcohol use was linked
      with social engagement in activities across both settings, and that moderate
      alcohol use appeared to serve an important function as a 'social lubricant'. The
      major facilitating factors for alcohol use included the frequency of
      opportunities for social engagement and access to a ready-made social group in
      retirement villages. The major constraining factor across both settings was
      driving. Interestingly, health was not viewed as a major facilitating or
      constraining factor for alcohol consumption. Conclusions from the research were
      that alcohol serves an important role in enhancing social engagement, and there
      appear to be important associations between residential setting and alcohol use. 

PMID- 24867130
TI  - Acute calcific tendinitis of the flexor pollicis longus in an 8-year-old boy.
AB  - Calcific tendinitis is a common source of musculoskeletal pain in adults;
      however, it is rarely encountered in children. Calcific tendinitis is the most
      commonly encountered manifestation of hydroxyapatite deposition disease, in which
      calcium hydroxyapatite crystal deposition occurs in tendons. It may cause acute
      or chronic pain, or may be entirely asymptomatic. We describe a case of acute
      calcific tendinitis of the flexor pollicis longus tendon in an 8-year-old boy,
      who initially presented to our department for workup of a mass felt along the
      volar aspect of the right wrist. 

PMID- 24867131
TI  - Does a picture tell a thousand words? The uses of digitally produced, multimodal
      pictures for communicating information about Alzheimer's disease.
AB  - This study explored the science communication potential of visual imagery by
      gauging an audience's interpretations of digitally enhanced, multimodal pictures
      depicting topics from recent Alzheimer's disease research. Guided by social
      semiotic theory, we created four pictures intended to communicate information
      about Alzheimer's disease unidirectionally, for an audience who had expressed
      interest in receiving such information (subscribers to an Alzheimer's disease
      research newsletter). We then disseminated the pictures to that audience via an
      online survey, to determine whether respondents received the messages we intended
      to convey. Our results demonstrated that, without accompanying explanatory text,
      pictures are most useful for evoking emotions or making loose connections between
      major concepts, rather than for communicating specific messages based on
      Alzheimer's research. In addition, participants more often expressed anger and
      frustration when the meaning of scientific imagery was unclear than when the
      meaning of emotional-social imagery was unclear. 

PMID- 24867133
TI  - Low levels of free testosterone correlated with bone mineral densities of femoral
      necks in aged healthy Shanghainese men.
AB  - The aim of the study was to investigate the influence of serum testosterone
      concentrations on bone mineral densities (BMDs) in healthy aged men in Shanghai
      area. Eighty-four participants, registered in the physical examination center of
      our hospital were included. Liquid chromatography tandem mass spectrometry (LC
      MS/MS) was used to measure concentrations of total testosterone (TT) and free
      testosterone (FT) in serum. BMDs of the lumbar spine, femoral neck, the
      trochanter major, and Ward's triangle were determined with dual energy X-ray
      absorptiometry (DXA). The correlations of TT and FT with BMDs at the different
      skeleton sites were analyzed; stratified analyses by age were performed with 10
      year range groups and the changing trends of TT and FT with increasing age were
      further investigated. In addition, we performed a stratified quartile TT and FT
      analysis of their correlations with BMDs of different bones in each group. The
      average age of the participants was 71.8 +/- 9.6 years (50-90 years). In a
      stratified analysis by age, no significant TT changes with increasing age was
      found, but there was a significant decrease of FT in men older than 80 years
      (p<0.05). In a stratified FT quartile analysis, FT in the first quartile group
      correlated significantly with BMDs of the lumbar spine, femoral neck and Ward's
      triangle; however, there was only a significant correlation between FT and BMD of
      the femoral neck after adjustment for age and body mass index (BMI). FT blood
      serum concentrations decreased significantly in healthy men aged over 80 and
      positively correlated with BMDs of femoral necks.

PMID- 24867134
TI  - Reduction in cortisol inactivation is part of the adrenal stress response to
      cardiac and noncardiac pediatric surgery: a prospective study using gas
      chromatography-mass spectrometry analysis.
AB  - We examined the hypothesis that major cardiac surgery triggers a more intense
      adrenal stress response than less intensive noncardiac surgery, which then alters
      cortisol inactivation. Urinary excretion rates of glucocorticoid metabolites were
      determined before and after surgery using gas chromatography-mass spectrometry in
      29 children undergoing scheduled major cardiac surgery and 17 control children
      undergoing conventional noncardiac surgery in a prospective observational study.
      Excretion rates of glucocorticoid metabolites were summed and corrected for
      creatinine excretion to calculate cortisol production rates (mg/mmol
      creatinine/m(2) body surface area). Precursor/product ratios from individual
      metabolites were calculated to characterize cortisol inactivation (11beta
      hydroxysteroid dehydrogenase). Postoperatively, median cortisol production rates
      increased in both groups ( MCS: from 2.7 to 9.3; controls: from 2.7 to 5.8;
      p<0.001) with no significant difference between groups (p=0.12). Ratios of
      cortisol to cortisone metabolites, indicating the overall activity of 11beta
      hydroxysteroid dehydrogenase, increased postoperatively in both groups (p<0.001).
      In conclusion, surgery resulted in a distinct postoperative increase in cortisol
      production. In contrast to our hypothesis, children undergoing major cardiac
      surgery did not show an increased adrenal stress response compared to children
      undergoing conventional surgery. Furthermore, the reduction in cortisol
      inactivation appears to be an essential part of the stress response to pediatric
      surgery in general.

PMID- 24867135
TI  - Gestational diabetes outcome in a single center study: higher BMI in children
      after six months.
AB  - The aim of the study was to examine obstetric outcomes and metabolic disorders in
      patients with gestational diabetes mellitus (GDM) and their offspring compared to
      mothers without GDM and their offspring. We performed a retrospective single
      center cohort study of mothers with GDM using a questionnaire with items
      concerning the maternal medical history, neonatal complications, and child
      development. Mothers with gestational diabetes (GDM; n=130) and those with normal
      glucose tolerance (NGT; n=77) were recruited. GDM mothers were older (37.58 years
      vs. 34.32 years, p<0.0001) and had a greater body mass index (25.18 kg/m2 vs.
      23.37 kg/m2, p<0.01). There were no significant differences regarding the mean
      birth weight, the frequency of Cesarean sections, and the prevalence of
      macrosomia (> 4 000 g). At follow-up (pediatric U5 screening visit after 6 months
      of birth) children of mothers with GDM had significantly higher BMI than the
      children of the NGT group (17.07 kg/m2 vs. 16.59 kg/m2, p=0.042). GDM women in
      need of insulin therapy during pregnancy had higher BMI than dieting GDM mothers
      and experienced more frequently an operative vaginal delivery (17.95% vs. 6.17%,
      OR 3.23, p=0.04). We found less significant differences between GDM mothers with
      treatment of impaired glucose tolerance and NGT mothers concerning the neonatal
      outcome than expected. Despite higher BMI of the GDM group's offspring at follow
      up U5 visit, the children did not show any other development disorder. In
      conclusion treatment of GDM could minimize the frequency of obstetric and
      neonatal complications in this risk group. 

PMID- 24867136
TI  - Risk factors of hyperthyroidism with hepatic function injury: a 4-year
      retrospective study.
AB  - Hepatic function injury is one of the common complications of hyperthyroidism
      (mainly Graves' disease), which affects the choice of treatment and the curative
      rate. Our goal was to describe clinical and biochemical patterns in patients
      suffering from Graves' disease (GD) and hepatic function injury and to determine
      the influential factors. A cohort of 1 070 patients who received (131)I treatment
      were studied. Many examinations were performed before (131)I therapy, such as:
      the 24-h radioactive iodine uptake of thyroid (RAIU(24 h)) and serum-free
      triiodothyronine (FT(3)), free thyroxine (FT(4)), sensitive thyroid-stimulating
      hormone (sTSH), antithyrotrophin receptor antibody (TRAb), thyroglobulin antibody
      (TgAb), and antithyroid peroxidase antibody (TPOAb), serum hepatic function
      tests, etc. Data were analyzed by the unpaired t-test, the independent samples t
      test, the chi(2) test, logistic regression, and Pearson bivariate correlation.
      Age, course of GD, thyroid's weight, FT(4), TPOAb, and TRAb in GD patients with
      hepatic function injury were higher than those with normal hepatic function
      patients. The influential factors were age, hyperthyroidism duration, heart rate,
      thyroid's weight, FT(4), RAIU(24 h), TgAb, TPOAb, and TRAb. RAIU(24 h) was the
      protecting factor. Age, course of GD, heart rate, thyroid's weight, FT(4), TRAb,
      and TPOAb were the risk factors. Patients whose age was higher than 45 years old,
      heart rate above 90 bpm, thyroid weight more than 35 g, the hyperthyroidism
      duration more than 3 years, FT(4) higher than 70.5 pmol/l, the level of TPOAb
      above 360 IU/ml, and the level of TRAb above 15 IU/l have increased risk of
      hepatic function injury. As treatment (131)I therapy was found to be the best
      choice.

PMID- 24867137
TI  - The thyroid axis 'setpoints' are significantly altered after long-term
      suppressive LT4 therapy.
AB  - The aim of the study was to investigate the changes in the thyroid axis setpoint
      after long-term suppressive levothyroxine therapy for differentiated thyroid
      carcinoma and the resulting changes in levothyroxine requirement. Ninety-nine
      differentiated thyroid cancer patients were reviewed. All patients had at least
      one known TSH-level>=0.01 mU/l (lower detection limit) and <1.0 mU/l within 2
      years of initial treatment (time 1) and had at least one TSH-value>=0.01 mU/l and
      <1.0 mU/l after continuous LT4 therapy for a minimum of 5 years (time 2).At time
      2 the mean LT4 dosage/kg body weight, TSH, FT3, and FT4 levels were significantly
      lower than at time 1, while body weight was higher. At time 2, the FT3/FT4 ratio
      rate had dropped significantly (p<0.001). At time 1, patients would require 2.96
      MUg/kg body weight to reach total TSH suppression. The dose of levothyroxine/kg
      required for suppression can be lowered by about 0.05 MUg/kg body weight for each
      year of suppressive therapy. After a median of 12.7 years of continuous
      suppressive levothyroxine therapy, patients would require 2.25 MUg/kg body weight
      (-23.5%) to reach total TSH-suppression. At least part of this reduction was
      independent of aging. As a result of changes in thyroid hormone metabolism and
      thyroid axis setpoint, long-term TSH-suppressive therapy contributes to a
      reduction in the dosage of levothyroxine per kilogram body weight required for
      full TSH suppression over time. 

PMID- 24867138
TI  - Comparison of therapeutic response to gonadotropin therapy between chinese male
      adolescents and young adults with hypogonadotropic hypogonadism caused by
      pituitary stalk interruption.
AB  - Hypogonadotropic hypogonadism (HH) is common in pituitary stalk interruption
      (PSI) patients. However, the optimal timing and effective regimen in the
      management of the pituitary-gonadal axis deficiency is still controversial. This
      study involved a retrospective review of 38 male patients with HH resulting from
      PSI. The HH patients were subdivided according to their ages into 2 experiment
      groups: Group I (adolescents, 14-18 years old, 25 cases) and Group II (young
      adults, 18-24 years old, 13 cases). To compare the therapeutic response to
      exogenous gonadotropin, a control analysis was carried out in the experimental
      groups with age-matched control groups. Before gonadotropin therapy, no
      significant increases in gonadal hormones were noted in either of the 2
      experimental groups. After treatment with human chorionic gonadotropin (hCG) for
      less than 6 months, the hormone levels of pituitary-gonadal axis significantly
      increased in group I than in group II. After adding the human menopause
      gonadotropin (hMG) for 6 months, the gonadal hormone levels of group II were
      significantly increased. In addition, the Tanner stage and penis lengths in group
      I were significantly improved. There was no significant adverse impact on BMI and
      height velocity (HV) after less than one year therapy. A prolonged
      hypogonadotropic period without treatment may be responsible for testicular
      dysfunction in HH males caused by PSI. Early supplementary therapy with hCG and
      hMG is beneficial for the recovery of gonadal hormone and development of
      secondary sexual characteristics. 

PMID- 24867139
TI  - Cerebral klotho protein as a humoral factor for maintenance of baroreflex.
AB  - The klotho protein produced by the choroid plexus is known as a humoral factor in
      central nervous system. Many hormones affecting the baroreflex sensitivity have
      been introduced in the brain. However, role of klotho in the baroreflex
      sensitivity is still unknown. Recently, mutations in the klotho gene have been
      linked to cardiovascular diseases in both animals and human subjects. Also,
      silencing of brain klotho has been reported to enhance cold-induced elevation of
      blood pressure. Thus, we investigated the role of klotho in maintenance of
      central cardiovascular reflex sensitivity. Male Wistar Kyoto (WKY) rats and
      spontaneously hypertensive rats (SHRs) were used. Either klotho shRNA or scramble
      shRNA was also ICV-infused into the brains of WKY rats to investigate the role of
      klotho in brain. Recombinant klotho or rat IgG was infused into the cerebral
      paraventricle (ICV) of SHRs for further understanding the role of klotho in
      hypertension. The baroreflex sensitivity was detected using the challenge with a
      depressor dose of sodium nitroprusside (SNP, 50 MUg/kg) or with a pressor dose of
      phenylephrine (PE, 8 MUg/kg). We found that silencing of klotho expression in the
      brain decreased the baroreflex sensitivity in WKY rats. Also, modulation of the
      blood pressure for one week altered the cardiovascular homeostasis and resulted
      in an increased expression of klotho in medulla oblongata. Moreover, the
      baroreflex sensitivity was restored in SHRs that received recombinant klotho
      through ICV brain. Thus, klotho is involved in the maintenance of baroreflex
      sensitivity in the brain.

PMID- 24867141
TI  - The endocannabinoid system--back to the scene of cardiometabolic risk factors
      control?
AB  - This review examines the impact of the endocannabinoid signaling system on
      metabolic and cardiovascular health and the new therapeutic strategies that
      selectively target dysfunctional endocannabinoid action in peripheral tissues,
      without causing the undesirable central nervous system effects that occurred with
      the first-generation of CB1 receptor blockers. We first review the components of
      the endocannabinoid system and the enzymes that synthesize and degrade the
      endocannabinoids, the critical role of the system in the homeostasis of energy
      balance, and its hedonic aspects related to the incentive and motivational value
      of food. Second, we describe the central and peripheral actions of the
      endocannabinoid system and its interactions with other biological modulators,
      such as ghrelin and leptin. Third, we summarize data from human clinical trials
      with the CB1 inverse agonist rimonabant, showing that the drug, although
      effective in increasing weight loss with accompanying improvements in the
      metabolic profile of the participants in the RIO (Rimonabant In Obesity) trials,
      was withdrawn from the market because of the risk of serious adverse events.
      Finally, we describe: 1) the development of new selective peripheral blockers
      that interrupt endocannabinoid action selectively in peripheral tissues and that
      have been suggested as an alternative approach to treat the metabolic
      consequences of obesity and related diseases, without undesirable central nervous
      system effects, and 2) the potential for inhibition of enzymes of synthesis, as
      well as the possible role of endocannabinoid congeners, with opposing effects as
      compared to CB1 receptor agonists, in the control of metabolic disorders. 

PMID- 24867140
TI  - Dehydroepiandrosterone administration increased trabecular mass and
      dihydrotestosterone levels in the cancellous region of the tibia in young female
      rats.
AB  - The aim of the present study was to determine whether dehydroepiandrosterone
      (DHEA) administration affects bone mass and local sex hormone levels in the
      cancellous region of young female rats. Eleven female rats (6 weeks old) were
      randomly divided into 2 groups: control rats (CON, n=5) and rats treated with
      DHEA (DHEA, n=6). DHEA dissolved in sesame oil was administered to the DHEA group
      intraperitoneally at 20 mg DHEA/kg body weight, and the CON group was treated
      with vehicle only (sesame oil, 0.5 ml). The rats were treated with DHEA or
      vehicle for 3 consecutive days, followed by 1 day of no treatment. The
      experimental period was 8 weeks. According to dual-energy X-ray absorptiometry
      and high-resolution microcomputed tomography data, the DHEA group exhibited
      increased trabecular bone mineral density (BMD), bone volume, and tibial
      thickness compared to the findings in the CON group, whereas no effect was
      observed on cortical BMD or morphometry. The concentrations of free testosterone
      and estradiol in the cancellous region of the tibia did not differ between the 2
      groups, but the DHT concentration was significantly higher in the DHEA group than
      in the CON group. These findings suggest that an increase in local DHT levels may
      stimulate an increase in trabecular bone mass during growth phases in female
      rats. 

PMID- 24867142
TI  - Flow-assisted 2D polymorph selection: stabilizing metastable monolayers at the
      liquid-solid interface.
AB  - Controlling crystal polymorphism constitutes a formidable challenge in
      contemporary chemistry. Two-dimensional (2D) crystals often provide model systems
      to decipher the complications in 3D crystals. In this contribution, we explore a
      unique way of governing 2D polymorphism at the organic liquid-solid interface. We
      demonstrate that a directional solvent flow could be used to stabilize
      crystalline monolayers of a metastable polymorph. Furthermore, flow fields active
      within the applied flow generate millimeter-sized domains of either polymorph in
      a controlled and reproducible fashion. 

PMID- 24867143
TI  - Paraneoplastic polyarteritis nodosa with cerebral masses: case report and
      literature review.
AB  - Polyarteritis nodosa (PAN) as a paraneoplastic vasculitis is rarely described,
      especially in association with squamous cell carcinoma (SCC). Furthermore, only
      5% of all PAN patients have central nervous system (CNS) involvement, almost
      exclusively in the form of cerebral infarction or intracerebral haemorrhage. We
      report the first case of PAN with multiple immunosuppressant-responsive, cerebral
      vasculitic lesions in association with metastatic SCC. 

PMID- 24867144
TI  - Vertically pi-expanded imidazo[1,2-a]pyridine: the missing link of the puzzle.
AB  - The dehydrogenative coupling of imidazo[1,2-a]pyridine derivative has been
      achieved for the first time. In cases in which the most-electron-rich position of
      the electron-excessive heterocycle was blocked by a naphthalen-1-yl substituent,
      neither oxidative aromatic coupling nor reaction under Scholl conditions enabled
      the fusion of the rings. The only method that converted the substrate into the
      corresponding imidazo[5,1,2-de]naphtho[1,8-ab]quinolizine was coupling in the
      presence of potassium in anhydrous toluene. Moreover, we discovered new,
      excellent conditions for this anion-radical coupling reaction, which employed dry
      O2 from the start in the reaction mixture. This method afforded vertically fused
      imidazo[1,2-a]pyridine in 63% yield. Interestingly, whereas the fluorescence
      quantum yield (Phi(fl)) of compound 3, despite the freedom of rotation, was close
      to 50%, the Phi(fl) value of flat naphthalene-imidazo[1,2-a]pyridine was only 5%.
      Detailed analysis of this compound by using DFT calculations and a low
      temperature Shpol'skii matrix revealed phosphorescence emission, thus indicating
      that efficient intersystem-crossing from the lowest-excited S1 level to the
      triplet manifold was the competing process with fluorescence.

PMID- 24867145
TI  - Chance and necessity in biochemistry: implications for the search for
      extraterrestrial biomarkers in Earth-like environments.
AB  - In this paper, we examine a restricted subset of the question of possible alien
      biochemistries. That is, we look into how different life might be if it emerged
      in environments similar to that required for life on Earth. We advocate a
      principle of chance and necessity in biochemistry. According to this principle,
      biochemistry is in some fundamental way the sum of two processes: there is an
      aspect of biochemistry that is an endowment from prebiotic processes, which
      represents the necessity, plus an aspect that is invented by the process of
      evolution, which represents the chance. As a result, we predict that life
      originating in extraterrestrial Earth-like environments will share biochemical
      motifs that can be traced back to the prebiotic world but will also have
      intrinsic biochemical traits that are unlikely to be duplicated elsewhere as they
      are combinatorially path-dependent. Effective and objective strategies to search
      for biomarkers, and evidence for a second genesis, on planets with Earth-like
      environments can be built based on this principle.

PMID- 24867146
TI  - A Case of Giant Thrombosed Persistent Primitive Trigeminal Artery Aneurysm
      Presenting with Trigeminal Neuralgia and Successfully Treated by a Covered Stent:
      Case Report and Review of Literature.

PMID- 24867147
TI  - To treat or not to treat: should psychologists treat tobacco use disorder?
AB  - The author presented this Presidential Address for Divison 18, Psychologists in
      Public Service, at the 2012 American Psychological Association Convention in
      Orlando, Florida. The address challenges public service psychologists to reduce
      the tobacco disease burden through their roles as researchers, leaders,
      educators, and practitioners and explains why treating tobacco use disorder is
      important and relevant for psychologists. The address discusses the prevalence
      and the resulting mortality and morbidity rates of tobacco use disorder, which
      call for effective evidence-based interventions that can be integrated by
      psychologists into other ongoing treatments. Treatment of the underserved
      populations, including those with serious mental illness and/or substance use
      disorders, presents many barriers. In addition, education and training for
      tobacco use disorder in undergraduate and graduate clinical psychology programs
      present further barriers for psychology trainees. However, progress is being made
      because of the numerous resources and psychology leaders who are advocates for
      tobacco use disorder treatment and research. Challenges for the future include
      increasing awareness of the importance of treatment for tobacco use disorder,
      finding innovative ways to increase access to comprehensive evidence-based
      treatment, and acknowledging that psychologists can make a difference in reducing
      the tobacco use disorder disease burden. Psychologists have an ethical and
      professional responsibility to treat tobacco use disorder.

PMID- 24867149
TI  - Re: Jim C. Hu, Giorgio Gandaglia, Pierre I. Karakiewicz, et al. Comparative
      effectiveness of robot-assisted versus open radical prostatectomy cancer control.
      Eur Urol 2014;66:666-72.

PMID- 24867153
TI  - Hit-and-run lymphomagenesis by the Bcl6 oncogene.

PMID- 24867148
TI  - Independent component analysis of resting state activity in pediatric obsessive
      compulsive disorder.
AB  - Obsessive-compulsive disorder (OCD) is an often severely disabling illness with
      onset generally in childhood or adolescence. Little is known, however, regarding
      the pattern of brain resting state activity in OCD early in the course of
      illness. We therefore examined differences in brain resting state activity in
      patients with pediatric OCD compared with healthy volunteers and their clinical
      correlates. Twenty-three pediatric OCD patients and 23 healthy volunteers (age
      range 9-17), matched for sex, age, handedness, and IQ completed a resting state
      functional magnetic resonance imaging exam at 3T. Patients completed the
      Children's Yale Brown Obsessive Scale. Data were decomposed into 36 functional
      networks using spatial group independent component analysis (ICA) and logistic
      regression was used to identify the components that yielded maximum group
      separation. Using ICA we identified three components that maximally separated the
      groups: a middle frontal/dorsal anterior cingulate network, an anterior/posterior
      cingulate network, and a visual network yielding an overall group classification
      of 76.1% (sensitivity = 78.3% and specificity = 73.9%). Independent component
      expression scores were significantly higher in patients compared with healthy
      volunteers in the middle frontal/dorsal anterior cingulate and the
      anterior/posterior cingulate networks, but lower in patients within the visual
      network. Higher expression scores in the anterior/posterior cingulate network
      correlated with greater severity of compulsions among patients. These findings
      implicate resting state fMRI abnormalities within the cingulate cortex and
      related control regions in the pathogenesis and phenomenology of OCD early in the
      course of the disorder and prior to extensive pharmacologic intervention.

PMID- 24867154
TI  - Assessment of proteinuria in patients with chronic kidney disease stage 3:
      albuminuria and non-albumin proteinuria.
AB  - BACKGROUND AND OBJECTIVE: Proteinuria assessment is key in investigating chronic
      kidney disease (CKD) but uncertainty exists regarding optimal methods.
      Albuminuria, reflecting glomerular damage, is usually measured, but non-albumin
      proteinuria (NAP), reflecting tubular damage, may be important. This study
      investigated the prevalence and associations of albuminuria and NAP, and the
      optimum number of urine specimens required. METHODS: 1,741 patients with CKD
      stage 3, recruited from primary care, underwent medical history, clinical
      assessment, blood sampling, and submitted three early morning urine samples for
      albumin to creatinine ratio (uACR) and protein to creatinine ratios (uPCR).
      Albuminuria was defined as uACR >= 3 mg/mmol in at least two of three samples.
      Isolated NAP was defined as uPCR >= 17 mg/mmol in two of three samples and uACR
      <3 mg/mmol in all three. Prevalence and associations of albuminuria and NAP,
      degree of agreement between single uACR and average of three uACRs, and urine
      albumin to protein ratio (uAPR  =  uACR/uPCR) were identified. RESULTS:
      Albuminuria prevalence was 16% and NAP 6%. Using a <1 mg/mmol threshold for uACR
      reduced NAP prevalence to 3.6%. Independent associations of albuminuria were:
      males (OR 3.06 (95% CI, 2.23-4.19)), diabetes (OR 2.14 (1.53-3.00)), lower
      estimated glomerular filtration rate ((OR 2.06 (1.48-2.85) 30-44 vs 45-59), and
      high sensitivity CRP ((OR 1.70 (1.25-2.32)). NAP was independently associated
      with females (OR 6.79 (3.48-13.26)), age (OR 1.62 (1.02-2.56) 80 s vs 70-79) and
      high sensitivity CRP ((OR 1.74 (1.14-2.66)). Of those with uPCR >= 17 mg/mmol,
      62% had uAPR<0.4. Sensitivity of single uACR was 95%, specificity 98%, PPV 90%.
      Bland Altman plot one vs average of three uACRs showed: mean difference 0.0064
      mg/mmol (SD 4.69, limits of agreement -9.19 to +9.20, absolute mean difference
      0.837). CONCLUSIONS: In CKD stage 3, albuminuria has associations distinct from
      those of isolated NAP (except for inflammatory markers). Single uACR categorised
      albuminuria but average of three performed better for quantification.

PMID- 24867156
TI  - Radiofrequency ablation for Barrett's esophagus.
AB  - PURPOSE OF REVIEW: Several studies published in the last year that have provided
      evidence on the efficacy, durability and safety of radiofrequency ablation (RFA)
      in Barrett's esophagus are highlighted in this review. RECENT FINDINGS: RFA is
      well tolerated and efficacious in most but not all Barrett's esophagus patients
      with dysplasia and esophageal adenocarcinoma (EAC). Recent reports have described
      highly variable rates of disease recurrence. Disease progression may occur during
      initial therapy or after complete eradication in a small, difficult to identify
      subset of patients. Studies are underway to help determine the predictors of
      response and recurrence. Modifications in technique and target populations have
      been described in the last year as well. SUMMARY: Endoscopic mucosal resection
      and RFA are the cornerstones in the management of dysplasia and early EAC in
      Barrett's esophagus patients today. Despite the encouraging data on the
      effectiveness and safety of RFA, recurrence and progression of disease remain an
      issue in a subset of patients who are treated.

PMID- 24867155
TI  - Food and aeroallergens in eosinophilic esophagitis: role of the allergist in
      patient management.
AB  - PURPOSE OF REVIEW: Eosinophilic esophagitis is a clinicopathologic disease of
      increasing worldwide prevalence that is triggered by food antigens. The
      concurrent management of all of the atopic diseases affecting a single individual
      is likely to be important for successful long-term eosinophilic esophagitis
      management. This review covers the role of the allergist in eosinophilic
      esophagitis with a focus on the literature from the past 2  years. RECENT
      FINDINGS: Studies in the past 2  years document that testing for immediate and
      delayed allergic hypersensitivity to foods can be of utility in building
      elimination diets in children, but that this may not be the case in adults. In
      addition, it has been shown that a number of cells and interleukins involved in
      Th2 inflammation such as invariant natural killer T cells, basophils, and
      interleukin-9 are important in eosinophilic esophagitis pathogenesis. Finally,
      the role of foods in generating esophageal remodeling has been shown using murine
      models. SUMMARY: Recent studies support the role of the allergist in eosinophilic
      esophagitis management, especially for food allergen testing, interpretation, and
      the management of food allergies concurrent atopic diatheses. In addition,
      allergists have made significant research contributions in our understanding of
      eosinophilic esophagitis.

PMID- 24867157
TI  - Effects of bariatric surgery on gastroesophageal reflux.
AB  - PURPOSE OF REVIEW: Obesity and gastroesophageal reflux disease (GERD) are two
      prevalent conditions with important impact on health resource utilization around
      the world. Obesity is a known risk factor in the pathogenesis of GERD. When
      conservative measures fail, bariatric surgery remains the only option to lose
      weight and correct obesity-related comorbidities. The influence of bariatric
      surgery on GERD depends on which bariatric intervention is used. RECENT FINDINGS:
      Recent studies indicate that laparoscopic gastric banding and laparoscopic sleeve
      gastrectomy have little influence on preexisting GERD symptoms and findings, but
      some patients may develop GERD after laparoscopic sleeve gastrectomy. A number of
      studies have documented that laparoscopic Roux-en-Y gastric bypass improves GERD
      symptoms and findings, making it the preferred procedure for morbid obese
      patients with concomitant GERD. SUMMARY: Current findings provide good arguments
      for searching for and treating GERD in patients scheduled to undergo bariatric
      surgery. The presence of GERD might represent a relative contraindication for
      sleeve gastrectomy or gastric banding or both. Gastric bypass might be the
      procedure of choice in morbid obese patients with GERD symptoms or findings or
      both.

PMID- 24867158
TI  - Maternal methamphetamine use in pregnancy and long-term neurodevelopmental and
      behavioral deficits in children.
AB  - AIM: To describe neurodevelopmental and/or behavioral findings among a cohort of
      South African children exposed to maternal methamphetamine (MA) use during
      pregnancy. METHODS: Developmental assessments with the Griffiths Mental
      Developmental Scales (GMDS) were completed on a pilot cohort of 15 toddlers aged
      2-4 years with a known history of maternal MA use during pregnancy. These were
      compared to a matched cohort of 21 toddlers without a history of maternal MA use.
      Each child underwent formal auditory testing and vision screen. The Child
      Behavior Checklist (CBCL) was completed by a parent or caregiver. Cohorts were
      matched for age, gestational age at birth, socio-economic status and geographic
      distribution. RESULTS: Baseline characteristics were similar between the two
      groups. Most significant areas of poorer performance on GMDS in the
      Methamphetamine-exposed cohort was noted on the Personal-Social Ability Subscale
      (p<0.0001) and on the Hand and Eye Co-ordination Subscale (p=0.0002), while lower
      scores were also obtained on General Quotients (p=0.022). There were also
      significant concerns regarding aggressive behavior and attention
      deficit/hyperactivity on the CBCL for the exposed group, although this did not
      reach statistical significance. CONCLUSION: Among children exposed to maternal MA
      use during pregnancy, specific developmental and behavioral deficits were
      increased when compared to controls. This correlates well with available
      literature. Larger sample sizes would help further support these findings and
      more definitively distinguish behavioral deficits.

PMID- 24867159
TI  - Ag-SiO2-Er2O3 nanocomposites: highly effective upconversion luminescence at high
      power excitation and high temperature.
AB  - Rare Earth (RE) activated upconversion phosphors (UCPs), have demonstrated
      significant application potentials in some front fields, including solar energy
      conversion and bio-application. However, some bottleneck problems should be
      overcame, such as the lower upconversion efficiency, narrower excitation band,
      concentration-quenching and temperature-quenching. To solve these problems, the
      Ag-SiO2-Er2O3 nanocomposites were fabricated, in which the upconversion
      luminescence (UCL) of Er2O3 was white broadband. Through the interaction of Er2O3
      with surface plasmon (SP) of silver nanoparticles (SNPs), the threshold power for
      generating broadbands was suppressed largely in contrast to the Er2O3
      nanoparticles (NPs), while the UCL brightness was enhanced remarkably, ranging
      from several to 10(4) times, which strongly depended on the power density of
      excitation light. At excitation power density of 1.50 W/mm(2) of 980 nm light,
      the UCL intensity of Ag-SiO2-Er2O3 is 40-folds than the well-known
      NaYF4:Yb(3+),Er(3+) commercial powders. And more, it is also interesting to
      observe that the composites demonstrate two excitation bands extending of 780-980
      nm, highly improved UCL with elevated temperature and excitation power density.
      The UCL mechanism related to UCL enhancement was carefully studied.

PMID- 24867161
TI  - A coupled model of fast axonal transport of organelles and slow axonal transport
      of tau protein.
AB  - We have developed a model that accounts for the effect of a non-uniform
      distribution of tau protein along the axon length on fast axonal transport of
      intracellular organelles. The tau distribution is simulated by using a slow
      axonal transport model; the numerically predicted tau distributions along the
      axon length were validated by comparing them with experimentally measured tau
      distributions reported in the literature. We then developed a fast axonal
      transport model for organelles that accounts for the reduction of kinesin
      attachment rate to microtubules by tau. We investigated organelle transport for
      two situations: (1) a uniform tau distribution and (2) a non-uniform tau
      distribution predicted by the slow axonal transport model. We found that non
      uniform tau distributions observed in healthy axons (an increase in tau
      concentration towards the axon tip) result in a significant enhancement of
      organelle transport towards the synapse compared with the uniform tau
      distribution with the same average amount of tau. This suggests that tau may play
      the role of being an enhancer of organelle transport. 

PMID- 24867160
TI  - Polycyclic aromatic hydrocarbons (PAHs) in yerba mate (Ilex paraguariensis) from
      the Argentinean market.
AB  - Polycyclic aromatic hydrocarbons (PAHs) occurrence in 50 samples marketed in the
      main supermarkets from Argentina was surveyed. A high performance liquid
      chromatography (HPLC) method was applied with fluorescence detection (FLD) and UV
      VIS diodes array detector (DAD) for the analysis of 16 PAHs in "yerba mate" (Ilex
      paraguariensis), with recoveries higher than 89% and limits of detection and
      quantification lower than that found by other methodologies in previous studies.
      Contamination expressed as the sum of 16 analysed PAHs ranged between 224.6 and
      4449.5 MUg kg(-1) on dry mass. The contamination expressed as PAH4 (sum of
      benzo(a)pyrene, chrysene, benzo(a)anthracene and benzo(b)fluoranthene) varied
      between 8.3 and 512.4 MUg kg(-1). The correlation coefficient for PAH2 (sum of
      benzo(a)pyrene and chrysene) and PAH4 groups was 0.99, for PAH2 and PAH8 (sum of
      benzo(a)pyrene, chrysene, benzo(a)anthracene, benzo(b)fluoranthene,
      benzo(k)fluoranthene, benzo(g,h,i)perylene, dibenzo(a,h)anthracene and
      indeno(1,2,3cd) pyrene) 0.97 and for PAH4 and PAH8 0.98. 

PMID- 24867162
TI  - Maillard reaction products modulate gut microbiota composition in adolescents.
AB  - SCOPE: Scarce data are available concerning effects of certain bioactive
      substances such as Maillard reaction products (MRP) on the gut microbiota
      composition, and the question of how a diet rich in MRP affects gut microbiota in
      humans is still open. METHODS AND RESULTS: Two experiments were conducted. In
      expt. 1, adolescents consumed diets either high or low in MRP in a two-period
      crossover trial; in expt. 2, rats were fed diets supplemented or not with MRP
      model-systems. Intestinal microbiota composition in fecal (adolescents) or cecal
      (rat) samples was assessed by qPCR analysis. Negative correlations were found in
      the human assay between lactobacilli numbers and dietary advanced MRP (r = -0.418
      and -0.387, for hydroxymethylfurfural and carboxymethyl-lysine respectively, p <
      0.05), whereas bifidobacteria counts were negatively correlated with Amadori
      compounds intake. In the rat assay, total bacteria and lactobacilli were
      negatively correlated with MRP intake (r = -0.674,-0.675 and -0.676, for Amadori
      compounds, hydroxymethylfurfural and carboxymethyl-lysine respectively, p <
      0.05), but no correlations were found with bifidobacteria. CONCLUSIONS: Dietary
      MRP are able to modulate in vivo the intestinal microbiota composition both in
      humans and in rats, and the specific effects are likely to be linked to the
      chemical structure and dietary amounts of the different browning compounds.

PMID- 24867163
TI  - Cardiovascular manifestations in Marfan syndrome and related diseases; multiple
      genes causing similar phenotypes.
AB  - Cardiovascular abnormalities are the major cause of morbidity and mortality in
      Marfan syndrome (MFS) and a few clinically related diseases that share, with MFS,
      the pathogenic contribution of dysregulated transforming growth factor beta
      (TGFbeta) signaling. They include Loeys-Dietz syndrome, Shprintzen-Goldberg
      syndrome, aneurysm-osteoarthritis syndrome and syndromic thoracic aortic
      aneurysms. Unlike the causal association of MFS with mutations in an
      extracellular matrix protein (ECM), the aforementioned conditions are due to
      defects in components of the TGFbeta pathway. While TGFbeta antagonism is being
      considered as a potential new therapy for these heritable syndromes, several
      points still need to be clarified in relevant animal models before this strategy
      could be safely applied to patients. Among others, unresolved issues include
      whether elevated TGFbeta signaling is responsible for all MFS manifestations and
      is the common trigger of disease in MFS and related conditions. The scope of our
      review is to highlight the clinical and experimental findings that have forged
      our understanding of the natural history and molecular pathogenesis of
      cardiovascular manifestations in this group of syndromic conditions. 

PMID- 24867165
TI  - Targeting neutrophils in sepsis.
AB  - Sepsis continues to have a high mortality rate worldwide. The multi-step effects
      of this syndrome make it difficult to develop a comprehensive understanding of
      its pathophysiology and to identify a direct treatment. Neutrophils play a major
      role in controlling infection. Interestingly, the recruitment of these cells to
      an infection site is markedly reduced in severe sepsis. The systemic activation
      of Toll-like receptors and high levels of TNF-alpha and nitric oxide are involved
      in the reduction of neutrophil recruitment due to down-regulation of CXCR2 in
      neutrophils. By contrast, CCR2 is expressed in neutrophils after sepsis induction
      and contributes to their recruitment to organs far from the infection site, which
      contributes to organ damage. This review provides an overview of the recent
      advances in the understanding of the role of neutrophils in sepsis, highlighting
      their potential as a therapeutic target. 

PMID- 24867166
TI  - Brainstem and spinal reflex studies in patients with primary progressive freezing
      of gait.
AB  - Our aim was to investigate the extent and pattern of involved pathways using
      brainstem and spinal reflexes by comparing primary progressive freezing of gait
      (PPFOG) progressive supranuclear palsy (PSP) with FOG. Seven patients with PPFOG
      and age and sex matched seven PSP patients and 16 healthy subjects were included
      in the study. All subjects underwent blink reflex (BR), trigemino-cervical reflex
      (TCR), auditory startle reflex (ASR) and long latency flexor reflex (LLFR)
      investigations under the same conditions. All three groups had normal BR
      latencies. ASR probability was lowest in the PSP group and was highest in PPFOG
      (p=0.005). The presence rate of TCR was lowest in PSP and it was highest in PPFOG
      (p=0.007 for SC and p=0.023 for SCM). The presence rate and amplitude of LLFR (R
      II) were decreased in the PSP group (p=0.010 and p=0.031, respectively) whereas
      it was in a continuous pattern in some of PPFOG patients. ASR, TCR and LLFR were
      all inhibited in PSP and we suggest that suppression of all three reflexes is
      probably related to degeneration of brainstem reticular formation and basal
      ganglia connections. However, interestingly, in PPFOG, excitabilities of ASR and
      TCR circuits are increased suggesting loss of pathways mediating suprasegmental
      control. 

PMID- 24867167
TI  - The analysis of correlation between IL-1B gene expression and genotyping in
      multiple sclerosis patients.
AB  - IL-1B is released by monocytes, astrocytes and brain endothelial cells and seems
      to be involved in inflammatory reactions of the central nervous system (CNS) in
      multiple sclerosis (MS). This study aims to evaluate the expression level of IL
      1B mRNA in peripheral blood mononuclear cells (PBMCs), genotype the rs16944 SNP
      and find out the role of this SNP on the expression level of IL-1B in MS
      patients. We found that the expression level of IL-1B in MS patients increased
      3.336 times more than controls in PBMCs but the rs16944 SNP in the promoter
      region of IL-1B did not affect the expression level of this gene and there was
      not association of this SNP with MS in the examined population. Also, our data
      did not reveal any correlation between normalized expressions of IL-1B gene with
      age of participants, age of onset, and disease duration. 

PMID- 24867168
TI  - Complexes formed between DNA and poly(amido amine) dendrimers of different
      generations--modelling DNA wrapping and penetration.
AB  - This study deals with the build-up of biomaterials consisting of biopolymers,
      namely DNA, and soft particles, poly(amido amine) (PAMAM) dendrimers, and how to
      model their interactions. We adopted and applied an analytical model to provide
      further insight into the complexation between DNA (4331 bp) and positively
      charged PAMAM dendrimers of generations 1, 2, 4, 6 and 8, previously studied
      experimentally. The theoretical models applied describe the DNA as a semiflexible
      polyelectrolyte that interacts with dendrimers considered as either hard
      (impenetrable) spheres or as penetrable and soft spheres. We found that the
      number of DNA turns around one dendrimer, thus forming a complex, increases with
      the dendrimer size or generation. The DNA penetration required for the complex to
      become charge neutral depends on dendrimer generation, where lower generation
      dendrimers require little penetration to give charge neutral complexes. High
      generation dendrimers display charge inversion for all considered dendrimer sizes
      and degrees of penetration. Consistent with the morphologies observed
      experimentally for dendrimer/DNA aggregates, where highly ordered rods and
      toroids are found for low generation dendrimers, the DNA wraps less than one turn
      around the dendrimer. Disordered globular structures appear for high generation
      dendrimers, where the DNA wraps several turns around the dendrimer. Particularly
      noteworthy is that the dendrimer generation 4 complexes, where the DNA wraps
      about one turn around the dendrimers, are borderline cases and can form all types
      of morphologies. The net-charges of the aggregate have been estimated using zeta
      potential measurements and are discussed within the theoretical framework. 

PMID- 24867169
TI  - Roseibium aquae sp. nov., isolated from a saline lake.
AB  - A Gram-staining-negative bacterium, strain DSG-S4-2(T), was isolated from Dasugan
      Lake, a saline lake (salinity 3.1%, w/v) in Qaidam basin, Qinghai, China and its
      taxonomic position was determined by using a polyphasic approach. Cells of strain
      DSG-S4-2(T) were non-spore-forming rods, 0.5-0.8 um wide and 1.2-3.8 um long and
      motile by means of a single polar flagellum. Strain DSG-S4-2(T) was strictly
      heterotrophic and aerobic, catalase-positive and oxidase-negative. PufLM and coxL
      genes were present, bacteriochlorophyll a (BChl a) and a carotenoid pigment were
      produced. Growth was observed in the presence of 0-8.0% (w/v) NaCl (optimum, 1.0
      2.0%), at 20-40  degrees C (optimum, 35  degrees C) and pH 6.5-10.5 (optimum, pH
      7.5-8.0). Strain DSG-S4-2(T) contained Q-10 as the sole respiratory quinone. The
      polar lipids contained two aminolipids, diphosphatidylglycerol,
      phosphatidylglycerol, phosphatidylethanolamine,
      phosphatidylmonomethylethanolamine, sulphoquinovosyldiacylglyceride,
      phosphatidylcholine and some unknown phospholipids, like the other members of the
      genus Roseibium. The predominant fatty acid (>70%) was summed feature 8 (C(18 :
      1)omega7c and/or C(18 : 1)omega6c). The DNA G+C content was 61.4 mol% (determined
      from melting temperature). Phylogenetic trees (neighbour-joining, maximum
      likelihood and maximum-parsimony) based on 16S rRNA gene sequences showed that
      strain DSG-S4-2(T) was associated with the members of the genus Roseibium, with
      highest 16S rRNA gene sequence similarity to Roseibium denhamense OCh 254(T)
      (96.3%) and Roseibium hamelinense OCh 368(T) (96.3%). Based on the data presented
      above, it is concluded that strain DSG-S4-2(T) represents a novel species of the
      genus Roseibium, for which the name Roseibium aquae sp. nov. is proposed. The
      type strain is DSG-S4-2(T) ( = CGMCC 1.12426(T) = JCM 19310(T)).

PMID- 24867170
TI  - Granulicella cerasi sp. nov., an acidophilic bacterium isolated from cherry bark.
AB  - A novel acidobacterial strain, Sakura1(T), was isolated from pieces of cherry
      bark. Cells of strain Sakura1(T) were non-motile, rod-shaped and stained Gram
      negative. This strictly aerobic isolate was mesophilic but was able to grow at
      temperatures as low as 10  degrees C. Colonies were pink due to production of
      carotenoids, and its pigmentation was more pronounced in cells grown at lower
      temperature. This strain had endoglucanase activity. The main respiratory quinone
      was menaquinone-8, and major cellular fatty acids were iso-C(15 : 0), C(16 :
      1)omega7c and C(16 : 0). Phylogenetic analysis of 16S rRNA gene sequences
      revealed that the strain was closely related to species of the genus Granulicella
      in subdivision 1 of the phylum Acidobacteria. The closest relative was
      Granulicella paludicola OB1010(T) (97.1% 16S rRNA gene sequence similarity).
      While common characteristics were found among the isolate and species of the
      genus Granulicella, there were obvious differences between them such as their
      cell morphology, cellulolytic activity, and tolerance to low temperature and NaCl
      concentration. Based on phylogenetic and phenotypic findings, a novel species is
      proposed in the genus Granulicella with the name Granulicella cerasi sp. nov. The
      type strain is Sakura1(T) ( = NBRC 107139(T) = DSM 23641(T)).

PMID- 24867171
TI  - Paludibaculum fermentans gen. nov., sp. nov., a facultative anaerobe capable of
      dissimilatory iron reduction from subdivision 3 of the Acidobacteria.
AB  - A facultatively anaerobic, non-pigmented, non-spore-forming bacterium was
      isolated from a littoral wetland of a boreal lake located on Valaam Island,
      northern Russia, and designated strain P105(T). Cells of this isolate were Gram
      negative, non-motile rods coated by S-layers with p2 lattice symmetry. Sugars
      were the preferred growth substrates. Under anoxic conditions, strain P105(T) was
      capable of fermentation and dissimilatory Fe(III) reduction. End products of
      fermentation were acetate, propionate and H2. Strain P105(T) was a mildly
      acidophilic, mesophilic organism, capable of growth at pH 4.0-7.2 (optimum pH 5.5
      6.0) and at 4-35  degrees C (optimum at 20-28  degrees C). The major fatty acids
      were iso-C(15 : 0) and C(16 : 1)omega7c; the cells also contained significant
      amounts of 13,16-dimethyl octacosanedioic acid (isodiabolic acid). The major
      polar lipids were phosphocholine and phosphoethanolamine; the quinone was MK-8.
      The G+C content of the DNA was 60.5 mol%. 16S rRNA gene sequence analysis showed
      that strain P105(T) belongs to subdivision 3 of the Acidobacteria and is only
      distantly related (90% sequence similarity) to the only currently characterized
      member of this subdivision, Bryobacter aggregatus. The novel isolate differs from
      Bryobacter aggregatus in its cell morphology and ability to grow under anoxic
      conditions and in the presence of iron- and nitrate-reducing capabilities as well
      as quinone and polar lipid compositions. These differences suggest that strain
      P105(T) represents a novel genus and species, for which the name Paludibaculum
      fermentans gen. nov., sp. nov., is proposed. The type strain of Paludibaculum
      fermentans is P105(T) ( = DSM 26340(T) = VKM B-2878(T)).

PMID- 24867172
TI  - Bifidobacterium aesculapii sp. nov., from the faeces of the baby common marmoset
      (Callithrix jacchus).
AB  - Six Gram-positive-staining, microaerophilic, non-spore-forming, fructose-6
      phosphate phosphoketolase-positive bacterial strains with a peculiar morphology
      were isolated from faecal samples of baby common marmosets (Callithrix jacchus).
      Cells of these strains showed a morphology not reported previously for a
      bifidobacterial species, which resembled a coiled snake, always coiled or ring
      shaped or forming a 'Y' shape. Strains MRM 3/1(T) and MRM 4/2 were chosen as
      representative strains and characterized further. The bacteria utilized a wide
      range of carbohydrates and produced urease. Glucose was fermented to acetate and
      lactate. Strain MRM 3/1(T) showed a peptidoglycan type unique among members of
      the genus Bifidobacterium. The DNA base composition was 64.7 mol% G+C. Almost
      complete 16S rRNA, hsp60, clpC and rpoB gene sequences were obtained and
      phylogenetic relationships were determined. Comparative analysis of 16S rRNA gene
      sequences showed that strains MRM 3/1(T) and MRM 4/2 had the highest similarities
      to Bifidobacterium scardovii DSM 13734(T) (94.6%) and Bifidobacterium
      stellenboschense DSM 23968(T) (94.5%). Analysis of hsp60 showed that both strains
      were closely related to B. stellenboschense DSM 23968(T) (97.5% similarity);
      however, despite this high degree of similarity, our isolates could be
      distinguished from B. stellenboschense DSM 23968(T) by low levels of DNA-DNA
      relatedness (30.4% with MRM 3/1(T)). Strains MRM 3/1(T) and MRM 4/2 were located
      in an actinobacterial cluster and were more closely related to the genus
      Bifidobacterium than to other genera in the family Bifidobacteriaceae. On the
      basis of these results, strains MRM 3/1(T) and MRM 4/2 represent a novel species
      within the genus Bifidobacterium, for which the name Bifidobacterium aesculapii
      sp. nov. is proposed; the type strain is MRM 3/1(T) ( = DSM 26737(T) = JCM
      18761(T)).

PMID- 24867173
TI  - Actinophytocola sediminis sp. nov., an actinomycete isolated from a marine
      sediment.
AB  - A novel actinomycete strain, designated YIM M13705(T), was isolated from a marine
      sediment sample of the South China Sea and its characteristics were determined by
      a polyphasic approach. The slowly growing, Gram-stain-positive, aerobic strain
      produced branched substrate mycelium and aerial hyphae, and no diffusible pigment
      was produced on the media tested. At maturity, spore chains were formed on aerial
      hyphae and substrate mycelium was not fragmented. Whole-cell hydrolysates of the
      strain contained meso-diaminopimelic acid and galactose, glucose, ribose and
      rhamnose. The predominant menaquinones were MK-9(H4) and MK-10(H2). The polar
      lipids detected were diphosphatidylglycerol, phosphatidylethanolamine,
      hydroxyphosphatidylethanolamine, phosphatidylinositol and ninhydrin-positive
      phosphoglycolipids. The major fatty acid was iso-C(16 : 0). The G+C content of
      the genomic DNA was 68.2 mol%. On the basis of 16S rRNA gene sequence, the strain
      was shown to be most closely related to species of the genus Actinophytocola. DNA
      DNA hybridization relatedness values (<70%) of the isolate with its closest
      neighbour Actinophytocola xinjiangensis QAIII60(T) supported classification of
      the isolate as a representative of a novel species. On the basis of phylogenetic
      analysis, and phenotypic and genotypic data, it is concluded that the new isolate
      belongs to a novel species of the genus Actinophytocola, for which the name
      Actinophytocola sediminis sp. nov. (type strain YIM M13705(T) = DSM 45939(T) =
      BCRC 16956(T)) is proposed.

PMID- 24867175
TI  - Pseudoscardovia radai sp. nov., another representative of a new genus within the
      family Bifidobacteriaceae isolated from the digestive tract of a wild pig ( Sus
      scrofa scrofa ).
AB  - Presence of bifidobacteria and representatives of the new genus Pseudoscardovia
      within the family Bifidobacteriaceae in the digestive tract of wild pigs has been
      reported recently. Results based on comparative 16S rRNA gene sequence analysis
      of a new fructose-6-phosphate phosphoketolase-positive bacterial isolate
      originated from the small intestine of a wild pig revealed a relationship to
      Pseudoscardovia suis DPTE4T (96.8% sequence similarity). Phylogenetic and
      comparative analyses based on 16S rRNA, hsp60, xfp, fusA, tuf and rpoC partial
      gene sequences confirmed relationship of the new bacterial strain to
      Pseudoscardovia suis compared with bifidobacteria species occurring in the
      digestive tract of domestic and wild pigs. Differences in utilization of various
      substrates, production of enzymes, cell morphology, peptidoglycan structure,
      profile of cellular fatty acids and polar lipids between the new bacterial
      isolate designated as DPVI-TET3T and P. suis DPTE4T allow to establish a new
      bacterial taxon for which the name Pseudoscardovia radai sp. nov. (= DPVI/TET3T =
      CCM 7943T = DSM 24742T) was proposed.

PMID- 24867174
TI  - Sinosporangium siamense sp. nov., isolated from soil and emended description of
      the genus Sinosporangium.
AB  - An actinomycetes strain A-T 1946(T) that developed spherical sporangia containing
      non-motile spores on aerial mycelia was isolated from dry deciduous forest soil
      in Thailand. 16S rRNA gene sequence analysis indicated that strain A-T 1946(T)
      belongs to the genus Sinosporangium, being closely related to Sinosporangium
      album 6014(T) (98.8% sequence similarity). The DNA-DNA relatedness values were
      43.7-50.9%, which were significantly below 70% and differentiated strain A-T
      1946(T) from the closest species. The cell-wall peptidoglycan contained meso
      diaminopimelic acid. The whole-cell sugars contained rhamnose, ribose, madurose
      and glucose. The predominant menaquinone was MK-9(H2). The diagnostic
      phospholipids were diphosphatidylglycerol, phosphatidylethanolamine,
      phosphatidylmethylethanolamine, lysophosphatidylethanolamine,
      phosphatidylglycerol, phosphatidylinositol, phosphatidylinositol-mannoside, N
      acetylglucosamine-containing phospholipids, two unknown phosphoglycolipids and
      two unknown phospholipids. The predominant cellular fatty acids were unsaturated
      C(16 : 1) and C(17 : 1), and saturated C(16 : 0) and 10-methyl-C(17 : 0).
      Following an evaluation of phenotypic, chemotaxonomic and genotypic
      characteristics, the isolate is proposed to represent a novel species of genus
      Sinosporangium to be named Sinosporangium siamense sp. nov. The type strain is A
      T 1946(T) ( = BCC 29081(T) = NBRC 109515(T)). An emended description of the genus
      Sinosporangium is also provided.

PMID- 24867176
TI  - Amphiplicatus metriothermophilus gen. nov., sp. nov., a thermotolerant
      alphaproteobacterium isolated from a hot spring.
AB  - A thermotolerant, Gram-strain-negative, non-spore-forming and strictly aerobic
      bacterium, designated GU51(T), was isolated from Guhai hot spring in Jimsar
      county, Xinjiang province, north-west China. Each cell of strain GU51(T)
      consisted of an oval body and two symmetrical long (3-6 um) prosthecae. The
      strain moved by polar flagellum. Oxidase and catalase were produced. Strain
      GU51(T) grew within the ranges of 37-65  degrees C (optimum 48-50  degrees C),
      0.5-7.5% (w/v) NaCl (optimum 2-3%) and pH 6.0-9.0 (optimum pH 7.5). The major
      respiratory quinone detected was ubiquinone 10 (U-10) and the genomic DNA G+C
      content was 66.7+/-0.4 mol%. Major fatty acids (>5%) were C(16 : 0), C(18 :
      1)omega7c and 11-methyl C(18 : 1)omega7c. The polar lipids consisted of
      diphosphatidylglycerol, five glycolipids, phosphatidylglycerol and an unknown
      phospholipid. Phylogenetic analysis showed the closest relatives of strain
      GU51(T) were members of the genus Parvularcula with 92.3% 16S rRNA gene sequence
      similarity. On the basis of this polyphasic taxonomic characterization, it is
      suggested that strain GU51(T) represents a novel species of a new genus in the
      family 'Parvularculaceae', for which the name Amphiplicatus metriothermophilus
      gen. nov., sp. nov. is proposed. The type strain of the type species is GU51(T) (
      = CGMCC 1.12710(T) = JCM 19779(T)).

PMID- 24867179
TI  - A missed diagnosis of acromegaly during a female-to-male gender transition.
AB  - We present a case of a 46-year-old transgender male who, during his female-to
      male transition, presented with a pituitary apoplexy at the emergency department
      of a general hospital in the Netherlands. During admission, it turned out that he
      also suffered from acromegaly due to a growth hormone secreting pituitary adenoma
      for which he was successfully treated at our university hospital. Previously, his
      complaints typical of acromegaly were dismissed as attributable to the gender
      transition. Without the apoplexy, the disease probably would have remained masked
      by the history of transgenderism for a much longer period of time. It is,
      therefore, essential to keep looking for additional explanations for new
      pathology and complaints that cannot typically be attributed to the gender
      transition in these patients. 

PMID- 24867177
TI  - Comparative effectiveness of vildagliptin in combination with other oral anti
      diabetes agents in usual-care conditions: the EDGE-Latin America study.
AB  - OBJECTIVE: To assess the proportion of patients on vildagliptin add-on dual
      therapy who respond to treatment over a 12 month follow-up, relative to
      comparator oral anti-diabetes dual therapy, in a usual care setting. RESEARCH
      DESIGN AND METHODS: Participants were patients with type 2 diabetes (T2DM) aged
      18 years and older from 311 centers in Argentina, Colombia, Ecuador, Mexico and
      Venezuela. Patients were taking monotherapy with an oral anti-diabetes drug
      (OAD), and were prescribed a new add-on OAD based on the judgment of their
      personal physician. According to this choice, patients were assigned to one of
      the two cohorts: vildagliptin or comparator OADs. MAIN OUTCOME MEASURES: The
      primary endpoint was the proportion of patients achieving an A1c drop >0.3%
      without edema, hypoglycemia, weight gain or discontinuation due to
      gastrointestinal (GI) events. The secondary endpoint was the proportion of
      patients with baseline A1c >=7% who reached the goal of an A1c <7% without
      hypoglycemia or weight gain. RESULTS: The per-protocol population (a subset of
      the intention-to-treat population that excluded patients with pre-specified
      protocol deviations) comprised 3773 patients, 3002 in the vildagliptin cohort and
      771 in the comparator cohort. The proportion of patients reaching the primary
      endpoint was higher in the vildagliptin cohort (60.3%) than the comparator cohort
      (50.7%), OR 1.48 (95% CI: 1.25-1.73). The same was observed for the secondary
      endpoint (44.8 versus 33.1%) OR 1.64 (95% CI: 1.37-1.98). The incidence of
      adverse events was low and similar between treatment cohorts. CONCLUSION: In a
      usual care setting, patients treated with a vildagliptin combination succeeded in
      lowering A1c to <7%, without weight gain, hypoglycemia or peripheral edema more
      often than patients treated with comparator combinations, without increased risk
      of adverse events. Key limitations are the observational nature of the study and
      its relatively limited 12 month timeframe.

PMID- 24867181
TI  - The unjustified doubt of add health studies on the health disparities of non
      heterosexual adolescents: comment on Savin-Williams and Joyner (2014).

PMID- 24867180
TI  - Male homosexual behavior in a free-ranging all-male group of Japanese macaques at
      minoo, Japan.
AB  - We documented nine male homosexual consortships within three different male-male
      dyads in a free-ranging all-male group of Japanese macaques (Macaca fuscata), at
      Minoo, Japan. A total of 63 male-male mounts were observed during these
      consortships. Male homosexual interactions shared most of the behavioral
      components that have been reported to characterize heterosexual and female
      homosexual consortships in this species. Convergent behavioral data, including
      analysis of male-male solicitations, mounting postures, body orientations, inter
      mount activities, and third-party male intrusions supported the conclusion that
      male-male consortships are a sexual phenomenon. We discussed a series of
      proximate and ultimate hypotheses that purport to account for the occurrence of
      male homosexual behavior in all-male groups of primates, including humans. This
      first report of male homosexual interactions in an all-male group of Japanese
      macaques contributes to the growing database used to provide insights into the
      developmental processes, causal mechanisms, adaptive significance, and
      phylogenetic pathways of same-sex sexual behavior. 

PMID- 24867182
TI  - Inter-year repeatability study of volatile organic compounds from surface
      decomposition of human analogues.
AB  - Decomposition odour and volatile organic compounds (VOCs) have gained
      considerable attention recently due to their use by insects and scent detection
      canines to locate remains. However, a comprehensive and accurate profile of
      decomposition odour is yet to be confirmed. This is, in part, due to the
      geographical diversity in the studies conducted and the variation in the
      methodology and compounds being reported. To date, no repeatability studies of
      decomposition odour have been conducted in the same environment. In order to
      address this current gap in the scientific literature, this study conducted three
      replicate trials in order to evaluate the inter-year repeatability of the
      decomposition VOC profile in a southern Canadian environment. Surface
      decomposition trials were conducted during the spring and summer months and the
      VOCs were analysed by thermal desorption-gas chromatography-mass spectrometry (TD
      GC-MS). This study was able to demonstrate that decomposition VOCs are produced
      consistently during their characteristic stages and that this relationship is
      maintained under varying environmental factors which influence the rate of
      decomposition. This consistent production of decomposition VOCs can lead to a
      better understanding of the mechanisms of soft tissue decomposition and their
      sources of variation, and it could potentially lead to improved applications of
      these compounds for the detection of decomposed remains. 

PMID- 24867184
TI  - Expression of ampC, oprD, and mexA, outer membrane protein analysis and
      carbapenemases in multidrug resistant clinical isolates of Pseudomonas aeruginosa
      from Egypt.

PMID- 24867183
TI  - Prevalence and clinical relevance of T-helper cells, Th17 and Th1, in hepatitis B
      virus-related hepatocellular carcinoma.
AB  - BACKGROUND AND AIMS: An immune imbalance in the cytokine profile exerts a
      profound influence on the progression of hepatitis B virus (HBV) infections and
      hepatocellular carcinoma (HCC). The present study evaluated the immune status of
      T helper (Th) 17 and Th1 cells in patients with HBV-related and non-HBV-related
      HCC. METHODS: We randomly enrolled 150 patients with HCC. Blood samples and
      tissue samples were obtained. The distributions and phenotypic features of Th17
      and Th1 cells were determined by flow cytometry and/or immunohistochemistry.
      RESULTS: Compared to corresponding non-tumor regions, the levels of Th17 and Th1
      cells were significantly increased in tumors of patients with HCC (P<0.001). The
      intratumoral densities of IL-17-producing cells and IFN-gamma-producing cells
      were associated with overall survival (OS, P = 0.001) and disease-free survival
      (DFS, P = 0.001) of patients with HCC. The ratio of Th17 to Th1 in HBV-related
      HCC was higher than in non-HBV-related HCC. A multivariate Cox analysis revealed
      that the Th17 to Th1 ratio was an independent prognostic factor for OS (HR =
      2.651, P = 0.007) and DFS (HR = 2.456, P = 0.002). CONCLUSIONS: HBV infections
      can lead to an imbalance in immune status in patients with HCC. An elevated Th17
      to Th1 ratio may promote tumor progression. The Th17 to Th1 ratio could serve as
      a potential prognostic marker for scoring the severity of HCC.

PMID- 24867187
TI  - Is lymphocytic thyroiditis a unique type or merely a type of Hashimoto's
      thyroiditis?
AB  - AIM: Objective of the study was to clarify the role of apoptosis in the
      pathogenesis of lymphocytic thyroiditis (LT) and the existence of difference
      between Hashimoto's thyroiditis (HT) and LT. METHODS: We evaluated levels of
      antithyroglobulin and antithyroperoxidase antibodies, the apoptosis by in situ
      Cell Death Detection-TUNEL and the expression of Bcl2 and Bax by
      immunohistochemistry in thyroid tissues from 16 patient with HT, 10 with LT and
      10 with euthyroid goiter-EG (control group). RESULTS: It was found that apoptosis
      of thyrocytes in HT (mean 3.05%, SD 1.29%) and LT (mean 2.70%, SD 1.17%) was
      statistically significantly higher than EG (mean 0.56%, SD 0.23%), but the
      difference in the percentage of thyrocytes between HT and LT was not
      statistically significant. In HT the percentage of apoptotic infiltrating
      lymphocytes (mean 0.59%, SD 0.23%) was smaller than in EG (mean 2.26%, SD 1.42%),
      but it showed no significant difference in comparison to LT. The expression of
      Bax in infiltrating lymphocytes in HT (mean 0.72%, SD 0.34%) was statistically
      significantly higher than LT (mean 0.11%, SD 0.06%). The level of thyroglobulin
      was lower in HT compared to LT (P<0.01) and compared to EG (P<0.01). The level of
      antithyroglobulin/antithyroperoxidase antibodies was higher in HT compared to LT
      (P<0.01) and compared to EG (P<0.01). There was no statistically significant
      difference in the level of thyroglobulin and level of antibodies between LT and
      EG. CONCLUSION: These results suppose that apoptosis represents one of
      significant mechanisms in the pathogenesis of both HT and LT and that LT probably
      differs from HT.

PMID- 24867188
TI  - Reducing fall risk in the elderly: risk factors and fall prevention, a systematic
      review.
AB  - Falls in the elderly are a major source of injury resulting in disability and
      hospitalization. They have a significant impact on individual basis (loss of
      quality of live, nursing home admissions) and social basis (healthcare costs).
      Even though falls in the elderly are common there are some well studied risk
      factors. Special emphasis should be put on sarcopenia/frailty, polypharmacy,
      multimorbidity, vitamin D status and home hazards. There are several well
      evaluated fall prevention approaches that either target a single fall risk factor
      or focus on multiple risk factors. It has to be kept in mind that not all fall
      prevention strategies are useful for all patients as for example dietary
      substitution of vitamin D is only recommended in people with increased risk for a
      vitamin D deficiency. Home hazard reduction strategies are more effective when
      combined with other fall prevention approaches such as for example exercise
      programs. In conclusion elderly patients should routinely be screened for
      relevant risk factors and if need an indiviudally targeted fall prevention
      program compiled.

PMID- 24867189
TI  - The problem of an incidental uniloculated cyst.
AB  - Incidental uniloculated cysts are diagnosed more frequently due to the increase
      in availability of high-quality abdominal imaging. The prevalence of incidental
      pancreatic cysts detected on abdominal imaging is 2.6% and is even higher in old
      patients. Pancreatic cysts are also found in up to 25% of autopsies, 3% of which
      present progression to carcinoma in situ. The most frequently incidental cysts
      detected are <10 mm in size and the spectrum has changed from inflammatory to
      mucinous lesions. Although some morphological and cytological features can help
      to establish the nature of these cysts, it is unclear how many of them carry a
      risk of malignant degeneration, how to identify those accurately, and, once
      recognized, how to establish which ones are likely to harbor incipient cancer and
      how to manage them. In the last years, some guidelines have been elaborated that
      summarize all the evidence published up to now and provide clinicians with useful
      recommendations regarding the management of pancreatic uniloculated cysts. 

PMID- 24867192
TI  - Melatonin prevents maternal fructose intake-induced programmed hypertension in
      the offspring: roles of nitric oxide and arachidonic acid metabolites.
AB  - Fructose intake has increased globally and is linked to hypertension. Melatonin
      was reported to prevent hypertension development. In this study, we examined
      whether maternal high fructose (HF) intake causes programmed hypertension and
      whether melatonin therapy confers protection against the process, with a focus on
      the link to epigenetic changes in the kidney using next-generation RNA sequencing
      (NGS) technology. Pregnant Sprague-Dawley rats received regular chow or chow
      supplemented with HF (60% diet by weight) alone or with additional 0.01%
      melatonin in drinking water during the whole period of pregnancy and lactation.
      Male offspring were assigned to four groups: control, HF, control + melatonin
      (M), and HF + M. Maternal HF caused increases in blood pressure (BP) in the 12-wk
      old offspring. Melatonin therapy blunted the HF-induced programmed hypertension
      and increased nitric oxide (NO) level in the kidney. The identified differential
      expressed gene (DEGs) that are related to regulation of BP included Ephx2,
      Col1a2, Gucy1a3, Npr3, Aqp2, Hba-a2, and Ptgs1. Of which, melatonin therapy
      inhibited expression and activity of soluble epoxide hydrolase (SEH, Ephx2 gene
      encoding protein). In addition, we found genes in arachidonic acid metabolism
      were potentially involved in the HF-induced programmed hypertension and were
      affected by melatonin therapy. Together, our data suggest that the beneficial
      effects of melatonin are attributed to its ability to increase NO level in the
      kidney, epigenetic regulation of genes related to BP control, and inhibition of
      SEH expression. The roles of DEGs by the NGS in long-term epigenetic changes in
      the adult offspring kidney require further clarification. 

PMID- 24867193
TI  - Interaction of amphiphilic alpha-helical cell-penetrating peptides with heparan
      sulfate.
AB  - Cell-penetrating peptides (CPPs) are able to be taken up by cells and can deliver
      macromolecular cargos. However, the mechanism of this internalization is not yet
      fully understood. Recent theories suggest that the binding of cationic CPPs to
      negatively charged extracellular glycosaminoglycans, such as heparan sulfate
      (HS), is a possible mechanism of cellular uptake (CU). Our group has screened the
      CU activities of 54 systematically designed amphiphilic alpha-helical peptides in
      HeLa cells. Notably, a mutation in even a single residue significantly alters the
      CU ability of a peptide. To determine the structure-CU activity relationship of
      CPPs, four peptides, which contain a difference in one or two amino acids (i.e.,
      Arg/Glu and Ala/Phe), were chosen from our CPP library to examine their
      interactions with HS. Fluorescence spectroscopy, isothermal titration calorimetry
      (ITC) and dynamic light scattering analysis indicated that the HS-binding
      affinities and HS-clustering abilities of the four CPPs correlated well with
      their CU activities in HeLa and A549 cells. The heat capacities of the CPPs,
      determined using ITC and binding free energy decomposition analyses in molecular
      dynamics simulations, revealed that electrostatic interactions were more dominant
      in the HS-binding processes of Arg-containing peptides in comparison to Glu
      containing peptides, whereas hydrophobic contributions were the primary mode of
      interaction of Phe-containing peptides in comparison to Ala-containing peptides.
      Furthermore, it was implied that hydrophobic interactions may be more favourable
      than electrostatic interactions during the CU process. 

PMID- 24867195
TI  - Electronically implemented clinical indicators based on a data warehouse in a
      tertiary hospital: its clinical benefit and effectiveness.
AB  - OBJECTIVE: Assessing and monitoring care and service using clinical indicators
      (CIs) can allow the measurement of and lead to improvements in the quality of
      care. However, the management and maintenance of CI data has been shown to be
      difficult because the data are usually collected and provided manually. In this
      study, for the purpose of efficient managing quality indicators, a data warehouse
      (DW)-based CI monitoring system was developed. The clinical effectiveness and
      efficiency of a DW-based CI monitoring was investigated through several case
      studies of the system's operation at a tertiary hospital. METHODS: This study
      analyzed the CIs that have been developed over the past 8 years at a 1340-bed
      tertiary general university hospital in South Korea to improve and monitor the
      quality of care and patient safety. The hospital was opened as a fully digital
      hospital in 2003, and the CIs were computerized in 2005 by implementing a DW
      based CI monitoring system. We classified the computerized CIs and evaluated the
      monitoring results for several representative CIs, such as the optimal
      prescribing of preventive antibiotics, the average length of stay, the mortality
      rate, and the rehospitalization rate. RESULTS: During the development of the
      system in 2005, 12 of 19 CIs were computerized, and this number gradually
      increased until 299 of 335 CIs were computerized by 2012. In addition, among the
      CIs built computationally through the CI task force team, focal CIs subject to
      monitoring were selected annually, and the results of this monitoring were shared
      with all of the staff or the related department and its staff. By providing some
      examples of our CI monitoring results, we showed the feasibility of improving the
      quality of care, and maintaining the optimum level of patient care with less
      labor. CONCLUSIONS: The results of this study provide evidence regarding the
      clinical effectiveness and efficiency as well as the systems operation experience
      of a DW-based CI monitoring system. These findings may aid medical institutions
      that plan on computerizing CIs with respect to decision and policy making
      regarding their systems development and operations.

PMID- 24867196
TI  - The importance of individual protein molecule dynamics in developing and
      assessing solid state protein preparations.
AB  - Processing protein solutions into the solid state is a common approach for
      generating stable amorphous protein mixtures that are suitable for long-term
      storage. Great care is typically given to protecting the protein native structure
      during the various drying steps that render it into the amorphous solid state.
      However, many studies illustrate that chemical and physical degradations still
      occur in spite of this amorphous material having good glassy properties and it
      being stored at temperatures below its glass transition temperature (Tg). Because
      of these persistent issues and recent biophysical studies that have refined the
      debate ascribing meaning to the molecular dynamical transition temperature and Tg
      of protein molecules, we provide an updated discussion on the impact of assessing
      and managing localized, individual protein molecule nondiffusive motions in the
      context of proteins being prepared into bulk amorphous mixtures. Our aim is to
      bridge the pharmaceutical studies addressing bulk amorphous preparations and
      their glassy behavior, with the biophysical studies historically focused on the
      nondiffusive internal protein dynamics and a protein's activity, along with their
      combined efforts in assessing the impact of solvent hydrogen-bonding networks on
      local stability. We also provide recommendations for future research efforts in
      solid-state formulation approaches.

PMID- 24867197
TI  - Pronator teres branch transfer to the anterior interosseous nerve for treating
      C8T1 brachial plexus avulsion: an anatomic study and case report.
AB  - BACKGROUND: The treatment of C8T1 avulsion is challenging for neurosurgeons.
      Various methods for the restoration of finger flexion are used. However, most of
      these methods have different disadvantages and cannot restore the full active
      range of motion of the fingers. OBJECTIVE: To determine the feasibility of the
      pronator teres branch transfer to the anterior interosseous nerve with anatomic
      study and to use this method in 1 case. METHODS: The upper limbs of 15 fresh
      cadavers were dissected to identify the main trunk of the median nerve, the
      pronator teres branch, and the anterior interosseous nerve. The mean number and
      length of the pronator teres branches were recorded. The anterior interosseous
      nerve was dissected atraumatically to the most proximal level where the fibers of
      the anterior interosseous nerve did not mingle with the fibers of the main trunk
      of the median, which was defined as the atraumatic level of the anterior
      interosseous nerve. A line joining the most protruding point of the medial
      condyle and lateral condyle of the humerus was used as a measurement landmark.
      Pronator teres branch transfer to the anterior interosseous nerve was performed
      in 1 patient with C8T1 avulsion. RESULTS: The mean number of the pronator teres
      branches was 2.37 +/- 0.49. The mean length of the pronator teres branches was
      9.64 +/- 0.71 mm. The mean distance between the point where the pronator teres
      branches originated and the landmark line was 3.87 +/- 0.34 mm. The mean distance
      between the atraumatic level of the anterior interosseous nerve and the landmark
      line was -5.46 +/- 0.73 mm. Transfer of the pronator teres was used to innervate
      the anterior interosseous nerve in 1 patient with C8T1 avulsion. When assessed 14
      months after the operation, a full active range of motion of the fingers had been
      restored, and the patient's finger flexor muscles had regained grade 4 power.
      CONCLUSION: The pronator teres can be transferred to the anterior interosseous
      nerve directly at the elbow level. This operation was performed successfully in 1
      patient, who exhibited finger flexion recovery.

PMID- 24867198
TI  - Executive summary of Concussion guidelines step 1: systematic review of prevalent
      indicators.

PMID- 24867199
TI  - The small-chamber irrigation technique (SCIT): a simple maneuver for managing
      intraoperative hemorrhage during endoscopic intraventricular surgery.
AB  - BACKGROUND: Acute intraoperative intraventricular hemorrhage is a feared event in
      endoscopic neurosurgical procedures. OBJECTIVE: To describe the small-chamber
      irrigation technique (SCIT) for intraoperative endoscopic management of
      intraventricular hemorrhage. METHODS: The SCIT was used in intraventricular
      surgery for hydrocephalus, intraventricular tumors requiring biopsy, arachnoid
      cysts, and colloid cysts. RESULTS: Intraventricular hemorrhage was successfully
      managed endoscopically with a combination of the SCIT, routine irrigation, and
      coagulation, allowing for completion of the primary procedures. CONCLUSION: The
      SCIT is a powerful tool that the neuroendoscopist can use for visualization to
      achieve hemostasis when performing intraventricular endoscopic surgery.

PMID- 24867200
TI  - Cervical perimedullary arteriovenous shunts: a study of 22 consecutive cases with
      a focus on angioarchitecture and surgical approaches.
AB  - BACKGROUND: Reports of cervical perimedullary arteriovenous shunt (PMAVS) are
      limited, and treatment strategies have not been established. OBJECTIVE: To
      describe angioarchitecture and optimal treatment strategies for cervical PMAVS.
      METHODS: We treated 22 patients with cervical PMAVS between 2000 and 2012 (8
      women and 14 men; age, 9-80 years). According to the classification, our patients
      included type IVa (4 patients), type IVb (16 patients), and type IVc (2
      patients). Seventeen patients presented with subarachnoid hemorrhage. RESULTS: A
      total of 41 shunting points were localized in 22 patients, of which 34 points
      were located ventral or ventrolateral to the spinal cord. The anterior spinal
      artery (ASA) contributed to the shunts in 16 patients. Aneurysm formation was
      identified in 8 patients. Endovascular treatment was attempted in 3 patients,
      resulting in complete obliteration in 1 patient (type IVc). Overall, 21 patients
      underwent open surgery. An anterior approach with corpectomy was elected for 2
      patients; the other 19 patients underwent the posterior approaches using
      indocyanine green videoangiography, intraoperative angiography, endoscopy (8
      patients), and neuromonitoring. Twenty patients were rated as having a good
      recovery at 6 months after surgery. No recurrence was observed in any patients
      during the follow-up (mean, 59.7 months). CONCLUSION: Shunting points of the
      cervical PMAVS were predominantly located ventral or ventrolateral to the spinal
      cord and were often fed by the ASA. Even for ventral lesions, posterior exposure
      assisted with neuromonitoring and endoscopy, and intraoperative angiography
      provided a view sufficient to understand the relationships between the shunts and
      the ASA and contributed to good surgical outcomes.

PMID- 24867201
TI  - Increasing flow diversion for cerebral aneurysm treatment using a single flow
      diverter.
AB  - BACKGROUND: A neurovascular flow diverter (FD), aiming at inducing embolic
      occlusion of cerebral aneurysms through hemodynamic changes, can produce variable
      mesh densities owing to its flexible mesh structure. OBJECTIVE: To explore
      whether the hemodynamic outcome would differ by increasing FD local compaction
      across the aneurysm orifice. METHODS: We investigated deployment of a single FD
      using 2 clinical strategies: no compaction (the standard method) and maximum
      compaction across the aneurysm orifice (an emerging strategy). Using an advanced
      modeling technique, we simulated these strategies applied to a patient-specific
      wide-necked aneurysm model, resulting in a relatively uniform mesh with no
      compaction (C1) and maximum compaction (C2) at the aneurysm orifice. Pre- and
      posttreatment aneurysmal hemodynamics were analyzed using pulsatile computational
      fluid dynamics. Flow-stasis parameters and blood shear stress were calculated to
      assess the potential for aneurysm embolic occlusion. RESULTS: Flow streamlines,
      isovelocity, and wall shear stress distributions demonstrated enhanced aneurysmal
      flow reduction with C2. The average intra-aneurysmal flow velocity was 29% of
      pretreatment with C2 compared with 67% with C1. Aneurysmal flow turnover time was
      237% and 134% of pretreatment for C2 and C1, respectively. Vortex core lines and
      oscillatory shear index distributions indicated that C2 decreased the aneurysmal
      flow complexity more than C1. Ultrahigh blood shear stress was observed near FD
      struts in inflow region for both C1 and C2. CONCLUSION: The emerging strategy of
      maximum FD compaction can double aneurysmal flow reduction, thereby accelerating
      aneurysm occlusion. Moreover, ultrahigh blood shear stress was observed through
      FD pores, which could potentially activate platelets as an additional aneurysmal
      thrombosis mechanism.

PMID- 24867202
TI  - Neurosurgical management of a painful subcutaneous nodule of the knee:
      angioleiomyoma.
AB  - BACKGROUND AND IMPORTANCE: Angioleiomyoma (ALM) is a rare, benign smooth muscle
      tumor that can occur anywhere in the body. Diagnosis is usually delayed due to
      the unfamiliar location and presentation of the lesion. This tumor is not
      frequently discussed in neurosurgical publications as part of the differential
      diagnosis of painful subcutaneous lesions. To our knowledge, this is the first
      report of a neurosurgical presentation of ALM within an extremity. CLINICAL
      PRESENTATION: A 42-year-old woman presented with more than 2 years of severe
      right knee pain. The patient had undergone several treatments, including a knee
      arthroscopy, all without significant relief. Magnetic resonance imaging performed
      with a fiducial marker placed directly on the point of tenderness demonstrated an
      8-mm subcutaneous nodule. The patient underwent complete excision of the lesion,
      guided by the placement of the fiducial marker and its correlation with the
      preoperative magnetic resonance imaging. Intraoperatively, the lesion was not
      found to be associated with a nerve; however, there was a small vessel adjacent
      to the lesion. Pathology demonstrated this lesion to be an ALM. The patient's
      symptoms had completely resolved without any new neurological parasthesias or
      deficits on follow-up. CONCLUSION: Neurosurgeons should keep ALM in the
      differential diagnosis of painful extremity lesions. Localization using a
      fiducial marker directly overlying the area of suspicion is useful for the
      neurosurgeon and also for the radiologist so that the lesion may not be
      overlooked. Unnecessary interventions for the patient may be avoided with
      appropriate diagnosis, and surgical resection provides complete cure of the
      symptoms.

PMID- 24867203
TI  - Commentary: unruptured brain arteriovenous malformations: what a tangled web they
      weave.

PMID- 24867204
TI  - Whole-sellar stereotactic radiosurgery for functioning pituitary adenomas.
AB  - BACKGROUND: Functioning pituitary adenomas (FPAs) can be difficult to delineate
      on postoperative magnetic resonance imaging, making them difficult targets for
      stereotactic radiosurgery (SRS). In such cases, radiation delivery to the entire
      sella has been utilized as a radiosurgical equivalent of a total hypophysectomy.
      OBJECTIVE: To evaluate the outcomes of a cohort of patients with FPA who
      underwent SRS to the whole-sellar region. METHODS: This is a retrospective review
      of patients who underwent whole-sellar SRS for FPA between 1989 and 2012. Sixty
      four patients met the inclusion criteria: they were treated with whole-sellar SRS
      following surgical resection for persistently elevated hormone levels, and (1) no
      visible lesions on imaging studies and/or (2) tumor infiltration of dura or
      adjacent venous sinuses observed at the time of a prior resection. The median
      radiosurgical volume covering sellar structures was 3.2 mL, with a median margin
      dose of 25 Gy. RESULTS: The median endocrine follow-up was 41 months; 22 (68.8%)
      patients with acromegaly, 20 (71.4%) patients with Cushing disease, and 2 (50.0%)
      patients with prolactinoma achieved endocrine remission. The 2-, 4-, and 6-year
      actuarial remission rates were 54%, 78%, and 87%, respectively. New-onset
      neurological deficit was found in 4 (6.3%) patients following treatment. New
      onset hypopituitarism was observed in 27 (43.5%) patients, with
      panhypopituitarism in 2 (3.2%). Higher margin/maximum dose were significantly
      associated with a higher remission rate and development of post-SRS
      hypopituitarism. CONCLUSION: Whole-sellar SRS for invasive or imaging-negative
      FPA following failed resection can offer reasonable rates of endocrine remission.
      Hypopituitarism following whole-sellar SRS is the most common complication.

PMID- 24867205
TI  - Surgical and conservative treatments of complete spontaneous posterior
      interosseous nerve palsy with hourglass-like fascicular constrictions: a
      retrospective study of 41 cases.
AB  - BACKGROUND: The surgical treatment of spontaneous posterior interosseous nerve
      (PIN) palsy with hourglass-like fascicular constriction (HLFC) remains
      controversial. OBJECTIVE: To review 41 patients with complete spontaneous PIN
      palsy with HLFC to clarify the necessity and choice of surgery. METHODS:
      Interfascicular neurolysis (NY), neurorrhaphy, and autografting were performed on
      10, 8, and 6 patients, respectively. The thinning extent of a nerve fasciculus
      <=0.25, 0.25 to 0.75, and >=0.75 was defined as mild, moderate, and severe
      constriction, respectively. Final British Medical Research Council muscle power
      grade >=4 was defined as good recovery. RESULTS: Ultrasound showed the number,
      location, and thinning extent of HLFC of PIN well, with results that were highly
      consistent with intraoperative measurements. Of the 17 conservatively treated
      patients, 13 recovered well. Of the 24 surgically treated patients, 20 recovered
      well. For NY, 8 patients with mild to moderate PIN constriction recovered well,
      but 2 patients with severe PIN constriction recovered poorly. For 16 patients
      with severe HLFC, 12 of 14 patients who underwent neurorrhaphy or autografting
      recovered well; the surgical effects were much better than those of 2 patients
      who had undergone NY. CONCLUSION: Ultrasound is a helpful diagnostic technique
      for spontaneous PIN palsy with HLFC. Surgery is necessary for PIN constriction if
      conservative treatments fail. Surgical choices depend largely on the thinning
      extent of the PIN constriction and the age of the patients. The outcomes of
      patients aged >=50 years were much worse. We suggest NY for mild to moderate, and
      neurorrhaphy or autografting for severe PIN constriction.

PMID- 24867206
TI  - Prognostic factors in the operative management of dedifferentiated sacral
      chordomas.
AB  - BACKGROUND: Dedifferentiated chordomas are rare high-grade malignant spinal
      tumors for which there is minimal information to help guide treatment. OBJECTIVE:
      To identify prognostic factors associated with increased risk of local
      recurrence, metastases, and reduced survival in a cohort of patients undergoing
      sacrectomy for de novo dedifferentiated sacral chordoma. METHODS: Ten patients
      undergoing sacrectomy for histologically confirmed dedifferentiated chordoma at a
      specialist center were reviewed. There were 6 male and 4 female patients with a
      mean age of 66.7 years (range, 57-80 years) and mean follow-up of 36.7 months
      (range, 3-98 months). Data on prognostic factors were collected. RESULTS: The
      commonest presenting symptom was lumbar/gluteal pain. Mean duration of
      preoperative symptoms was 3.6 months (range, 2-7 months). Local recurrence was
      seen in 7 patients; metastases occurred in 5 patients. After sacrectomy, 7
      patients died at a mean of 41 months (range, 3-98 months). Tumor size >10 cm in
      diameter, amount of dedifferentiation within the conventional chordoma,
      sacroiliac joint infiltration, and inadequate resection margins were associated
      with increased risk of recurrence and reduced survival. Surgical approach,
      cephalad extent of primary tumor, and adjuvant radiotherapy did not affect
      oncological outcomes. CONCLUSION: Dedifferentiated chordomas are aggressive
      malignant tumors with a higher risk of local recurrence, metastases, and early
      mortality than conventional chordomas. Tumor diameter >10 cm, marginal resection,
      and sacroiliac joint infiltration may be associated with increased risk of local
      recurrence and mortality. Those with a smaller burden of dedifferentiated disease
      (<1 cm) within the primary chordoma have a better prognosis. Patients should be
      counseled about these risks before surgery and should have regular follow-up for
      the detection of local recurrence and metastases.

PMID- 24867207
TI  - Carpal tunnel syndrome is associated with high fibrinogen and fibrinogen
      deposits.
AB  - BACKGROUND: Idiopathic carpal tunnel syndrome (ICTS) is a common entrapment
      neuropathy. Some cases of ICTS are linked to mutations of the transthyretin gene,
      whereas others are associated with systemic amyloidosis. The majority of ICTS
      cases are of unknown etiology. OBJECTIVE: To study molecular mechanisms of ICTS
      development. METHODS: A total of 71 ICTS patients and 68 control subjects were
      included in the study. The fibrinogen level was determined before surgery and its
      deposition in the transversal carpal ligament (TCL) was detected by
      immunohistochemistry, Western blot, and mass spectrometry. Fibrinogen interaction
      with other proteins was studied by immunoprecipitation assay. RESULTS: Plasma
      levels of the proinflammatory and hemostatic protein fibrinogen are elevated in
      ICTS patients. Other measured systemic inflammatory markers were not affected,
      and local inflammatory responses in TCL were absent. ICTS patients have shorter
      bleeding times, probably because of the elevated plasma levels of fibrinogen.
      Polymorphisms of the fibrinogen B promoter region were previously associated with
      increased plasma fibrinogen, but this association was not observed among patients
      with ICTS. Interestingly, we detected fibrinogen deposits in the TCL, whereas
      transcriptional activity of the fibrinogen genes was low. Amyloidogenic proteins,
      including transthyretin and alpha-synuclein, were also found in the TCL, whereas
      their local transcriptional activity was rather high. Finally, we demonstrated
      that fibrinogen interacts with transthyretin and alpha-synuclein in TCL lysates.
      CONCLUSION: Our data indicate that fibrinogen and other aggregation-prone
      proteins have potentially important roles in the pathogenesis of ICTS.

PMID- 24867208
TI  - Structural characterization of residual hemicelluloses from hydrothermal
      pretreated Eucalyptus fiber.
AB  - In this study, an environmental-friendly hydrothermal pretreatment of Eucalyptus
      fiber followed with alkali post-treatment was developed to produce bioethanol
      efficiently. This biorefinery process allowed all major components of biomass
      being converted into high value-added products. The chemical and structural
      features of the residual hemicelluloses isolated with alkali from the
      hydrothermal pretreated Eucalyptus fiber, were comparatively investigated. Sugar
      and spectral analyses indicated that the hemicelluloses were mainly composed of
      glucuronoxylans, and especially hemicelluloses prepared at higher temperature
      (180 degrees C) contained higher contents of glucomannans and alpha-glucan.
      Hydrothermal pretreatment resulted in a significant hydrolysis of the glycosidic
      linkages in xylan backbone, and thus the molecular weight of the hemicelluloses
      was significantly reduced from 56,520 to 7780g/mol with the increase of
      temperature. This suggested that a combination of hydrothermal pretreatment at
      low temperatures (100-140 degrees C) and alkali post-treatment was an effective
      technique for isolating of hemicelluloses from Eucalyptus fiber. 

PMID- 24867210
TI  - Neuroethics in a "psy" world. The case of Argentina.
AB  - Given the cultural psychoanalytic tradition that shapes the thought of
      Argentineans and their current skepticism with regard to neurosciences when it
      comes to understanding human behavior, this article addresses the question of how
      a healthy neuroethics can develop in the country.

PMID- 24867209
TI  - Expression of Hedgehog ligand and signal transduction components in mutually
      distinct isocitrate dehydrogenase mutant glioma cells supports a role for
      paracrine signaling.
AB  - Hedgehog (Hh) signaling regulates the growth of malignant gliomas by a ligand
      dependent mechanism. The cellular source of Sonic Hh ligand and mode of signaling
      have not been clearly defined due to the lack of methods to definitively identify
      neoplastic cells in glioma specimens. Using an antibody specific for mutant
      isocitrate dehydrogenase protein expression to identify glioma cells, we
      demonstrate that Sonic Hh ligand and the pathway components Patched1 (PTCH1) and
      GLI1 are expressed in neoplastic cells. Further, Sonic Hh ligand and its
      transcriptional targets, PTCH1 and GLI1, are expressed in mutually distinct
      populations of neoplastic cells. These findings support a paracrine mode of
      intratumoral Hh signaling in malignant gliomas. 

PMID- 24867211
TI  - Management of intended durotomy in minimally invasive intradural spine surgery:
      clinical article.
AB  - OBJECT: Minimally invasive surgery (MIS) has been increasingly used for the
      treatment of various intradural spinal pathologies in recent years. Although MIS
      techniques allow for successful treatment of intradural pathology, primary dural
      closure in MIS can be technically challenging due to a limited surgical corridor
      through the tubular retractor system. The authors describe their experience with
      23 consecutive patients from a single institution who underwent MIS for
      intradural pathologies, along with a review of pertinent literature. METHODS: A
      retrospective review of a prospectively collected surgical database was performed
      to identify patients who underwent MIS for intradural spinal pathologies between
      November 2006 and July 2013. Patient demographics, preoperative records,
      operative notes, and postoperative records were reviewed. Primary outcomes
      include operative duration, estimated blood loss, length of bed rest, length of
      hospital stay, and postoperative complications, which were recorded
      prospectively. RESULTS: Twenty-three patients who had undergone MIS for
      intradural spinal pathologies during the study period were identified. Fifteen
      patients (65.2%) were female and 8 (34.8%) were male. The mean age at surgery was
      54.4 years (range 30-74 years). Surgical pathologies included neoplastic (17
      patients), congenital (3 patients), vascular (2 patients), and degenerative (1
      patient). The most common spinal region treated was lumbar (11 patients),
      followed by thoracic (9 patients), cervical (2 patients), and sacral (1 patient).
      The mean operative time was 161.1 minutes, and the mean estimated blood loss was
      107.2 ml. All patients were allowed full activity less than 24 hours after
      surgery. The median length of stay was 78.2 hours. Primary sutured dural closure
      was achieved using specialized MIS instruments with adjuvant fibrin sealant in
      all cases. The rate of postoperative headache, nausea, vomiting, and diplopia was
      0%. No case of cutaneous CSF fistula or symptomatic pseudomeningocele was
      identified at follow-up, and no patient required revision surgery. CONCLUSIONS:
      Primary dural closure with early mobilization is an effective strategy with
      excellent clinical outcomes in the use of MIS techniques for intradural spinal
      pathology. Prolonged bed rest after successful primary dural closure appears
      unnecessary, and the need for watertight dural closure should not prevent the use
      of MIS techniques in this specific patient population.

PMID- 24867212
TI  - Commentary: Transcranial drug delivery for neurological disorders.

PMID- 24867213
TI  - Editorial: Current updates on association between Alzheimer's disease and type 2
      diabetes mellitus--volume II.

PMID- 24867214
TI  - Transport of soluble proteins through the Golgi occurs by diffusion via
      continuities across cisternae.
AB  - The mechanism of transport through the Golgi complex is not completely
      understood, insofar as no single transport mechanism appears to account for all
      of the observations. Here, we compare the transport of soluble secretory proteins
      (albumin and alpha1-antitrypsin) with that of supramolecular cargoes (e.g.,
      procollagen) that are proposed to traverse the Golgi by compartment progression
      maturation. We show that these soluble proteins traverse the Golgi much faster
      than procollagen while moving through the same stack. Moreover, we present
      kinetic and morphological observations that indicate that albumin transport
      occurs by diffusion via intercisternal continuities. These data provide evidence
      for a transport mechanism that applies to a major class of secretory proteins and
      indicate the co-existence of multiple intra-Golgi trafficking modes. 

PMID- 24867217
TI  - Neuronal connectome of a sensory-motor circuit for visual navigation.
AB  - Animals use spatial differences in environmental light levels for visual
      navigation; however, how light inputs are translated into coordinated motor
      outputs remains poorly understood. Here we reconstruct the neuronal connectome of
      a four-eye visual circuit in the larva of the annelid Platynereis using serial
      section transmission electron microscopy. In this 71-neuron circuit,
      photoreceptors connect via three layers of interneurons to motorneurons, which
      innervate trunk muscles. By combining eye ablations with behavioral experiments,
      we show that the circuit compares light on either side of the body and stimulates
      body bending upon left-right light imbalance during visual phototaxis. We also
      identified an interneuron motif that enhances sensitivity to different light
      intensity contrasts. The Platynereis eye circuit has the hallmarks of a visual
      system, including spatial light detection and contrast modulation, illustrating
      how image-forming eyes may have evolved via intermediate stages contrasting only
      a light and a dark field during a simple visual task. 

PMID- 24867215
TI  - Natural variation reveals that intracellular distribution of ELF3 protein is
      associated with function in the circadian clock.
AB  - Natural selection of variants within the Arabidopsis thaliana circadian clock can
      be attributed to adaptation to varying environments. To define a basis for such
      variation, we examined clock speed in a reporter-modified Bay-0 x Shakdara
      recombinant inbred line and localized heritable variation. Extensive variation
      led us to identify EARLY FLOWERING3 (ELF3) as a major quantitative trait locus
      (QTL). The causal nucleotide polymorphism caused a short-period phenotype under
      light and severely dampened rhythm generation in darkness, and entrainment
      alterations resulted. We found that ELF3-Sha protein failed to properly localize
      to the nucleus, and its ability to accumulate in darkness was compromised.
      Evidence was provided that the ELF3-Sha allele originated in Central Asia.
      Collectively, we showed that ELF3 protein plays a vital role in defining its
      light-repressor action in the circadian clock and that its functional abilities
      are largely dependent on its cellular localization. 

PMID- 24867216
TI  - A neural mechanism of speed-accuracy tradeoff in macaque area LIP.
AB  - Decision making often involves a tradeoff between speed and accuracy. Previous
      studies indicate that neural activity in the lateral intraparietal area (LIP)
      represents the gradual accumulation of evidence toward a threshold level, or
      evidence bound, which terminates the decision process. The level of this bound is
      hypothesized to mediate the speed-accuracy tradeoff. To test this, we recorded
      from LIP while monkeys performed a motion discrimination task in two speed
      accuracy regimes. Surprisingly, the terminating threshold levels of neural
      activity were similar in both regimes. However, neurons recorded in the faster
      regime exhibited stronger evidence-independent activation from the beginning of
      decision formation, effectively reducing the evidence-dependent neural modulation
      needed for choice commitment. Our results suggest that control of speed vs
      accuracy may be exerted through changes in decision-related neural activity
      itself rather than through changes in the threshold applied to such neural
      activity to terminate a decision. 

PMID- 24867220
TI  - Gene expression profiling reveals large regulatory switches between succeeding
      stipe stages in Volvariella volvacea.
AB  - The edible mushroom Volvariella volvacea is an important crop in Southeast Asia
      and is predominantly harvested in the egg stage. One of the main factors that
      negatively affect its yield and value is the rapid transition from the egg to the
      elongation stage, which has a decreased commodity value and shelf life. To
      improve our understanding of the changes during stipe development and the
      transition from egg to elongation stage in particular, we analyzed gene
      transcription in stipe tissue of V. volvacea using 3'-tag based digital
      expression profiling. Stipe development turned out to be fairly complex with high
      numbers of expressed genes, and regulation of stage differences is mediated
      mainly by changes in expression levels of genes, rather than on/off modulation.
      Most explicit is the strong up-regulation of cell division from button to egg,
      and the very strong down-regulation hereof from egg to elongation, that continues
      in the maturation stage. Button and egg share cell division as means of growth,
      followed by a major developmental shift towards rapid stipe elongation based on
      cell extension as demonstrated by inactivation of cell division throughout
      elongation and maturation. Examination of regulatory genes up-regulated from egg
      to elongation identified three potential high upstream regulators for this
      switch. The new insights in stipe dynamics, together with a series of new target
      genes, will provide a sound base for further studies on the developmental
      mechanisms of mushroom stipes and the switch from egg to elongation in V.
      volvacea in particular. 

PMID- 24867223
TI  - Serum creatinine measurements: evaluation of a questionnaire according to the
      ESUR guidelines.
AB  - BACKGROUND: The European Society of Urogenital Radiology (ESUR) propose
      measurements of serum creatinine levels in patients undergoing contrast-enhanced
      studies with a high probability of impaired renal function and therefore with a
      higher risk of CIN and NSF. PURPOSE: To determine whether the recommended
      questionnaire is able to select these patients. MATERIAL AND METHODS: Over a time
      period of 10 months the questionnaire was conducted in 1389 patients (725 women,
      654 men) before contrast administration for computed tomography (CT) or magnetic
      resonance imaging (MRI) examination. Serum creatinine (SCr) measurements and
      calculation of estimated glomerular filtration rate (eGFR) values were performed
      when one or more answers were positive. Eighty-one patients were excluded due to
      incomplete data. Statistical evaluation of the questionnaire was done
      retrospectively. RESULTS: Four hundred and ninety-nine patients (38%) gave one or
      more positive answers to the questionnaire. Of these, 71 (14%) had an eGFR <60
      mL/min/1.73 m(2), 31 (6%) had an eGFR <45 mL/min/1.73 m(2), and five (1%) had an
      eGFR <30 mL/min/1.73 m(2). Only the question concerning previous renal disease
      showed a significant correlation to an eGFR <60 mL/min/1.73 m(2) (P < 0.05) and
      <45 mL/min/1.73 m(2). Slight correlations with some other risk factors (renal
      disease, family history of renal disease, arterial hypertension with medication,
      analgetic medication with nephrotoxic drugs) were found for either a threshold of
      60 or 45 mL/min/1.73 m(2). In addition, there was a positive correlation with
      patient age. CONCLUSION: We propose to reduce the questionnaire to a smaller
      number of risk factors and consider a point-of-care (POC) SCr measurement for all
      patients aged >70 years without a recent eGFR value while referred for CT. For
      MRI a SCr measurement is not mandatory while using medium and lowest risk
      contrast agents.

PMID- 24867222
TI  - Diagnostic value of 3D fluid attenuated inversion recovery sequence in multiple
      sclerosis.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) is an indispensable tool in the
      diagnostic work-up of multiple sclerosis (MS). To date, guidelines suggest MRI
      protocols containing axial dual-echo, unenhanced and post-contrast T1-weighted
      sequences. Especially the usage of dual-echo sequences has markedly improved the
      ability of MRI to detect cortical and infratentorial lesions. Newer 3D FLAIR
      sequences are supposed to provide even more positive imaging features such as
      improved detection of white matter lesions and a better resolution due to smaller
      slice thickness. PURPOSE: To evaluate the diagnostic impact of 3D FLAIR sequences
      in comparison to conventional T2 and PD sequences. MATERIAL AND METHODS:
      Examinations of 20 MS patients (10 women, 10 men) were reviewed retrospectively.
      All patients received MRI standard protocol containing PD and T2 sequences and a
      mid-sagittal T2 sequence. Additionally an isotropic 3D FLAIR sequence was
      performed. Whole-brain lesion load and number of lesions in juxtacortical,
      infratentorial, and midcallosal localizations were assessed by two observers
      independently and compared. RESULTS: Whole lesion load and the count of
      detectable lesions at the 3D FLAIR sequence were significantly higher in the
      juxtacortical and infratentorial regions compared to the PD/T2 sequence.
      Detection rate of midcallosal lesions did not differ significantly in sagittal T2
      and 3D FLAIR sequence. CONCLUSION: 3D FLAIR sequences can improve the detection
      of brain lesions in patients with MS and are even more sensitive in depicting
      lesions in cortical and infratentorial locations than current dual-echo
      sequences. The sequence can replace both PD/T2 sequences and mid-sagittal T2
      sequences of the corpus callosum.

PMID- 24867224
TI  - Occupational therapy interventions for adults with rheumatoid arthritis: an
      appraisal of the evidence.
AB  - This article identifies and critically appraises six systematic reviews published
      from 2007 to 2013 that assessed the efficacy of interventions used by
      occupational therapists for adults with rheumatoid arthritis. Results suggest
      there is sufficient evidence to support the use of therapeutic exercise, patient
      education through joint protection, and splinting for pain, inflammation, and
      grip strength but insufficient evidence to support the use of Tai Chi. To help
      guide clinical practice, future studies need to focus on the appropriate levels
      of intensity and combinations of therapeutic exercise, effective use of
      splinting, efficacy of specific education programs, and the use of Tai Chi as
      these relate to important patient outcomes.

PMID- 24867218
TI  - Cell elongation is regulated through a central circuit of interacting
      transcription factors in the Arabidopsis hypocotyl.
AB  - As the major mechanism of plant growth and morphogenesis, cell elongation is
      controlled by many hormonal and environmental signals. How these signals are
      coordinated at the molecular level to ensure coherent cellular responses remains
      unclear. In this study, we illustrate a molecular circuit that integrates all
      major growth-regulating signals, including auxin, brassinosteroid, gibberellin,
      light, and temperature. Analyses of genome-wide targets, genetic and biochemical
      interactions demonstrate that the auxin-response factor ARF6, the
      light/temperature-regulated transcription factor PIF4, and the brassinosteroid
      signaling transcription factor BZR1, interact with each other and cooperatively
      regulate large numbers of common target genes, but their DNA-binding activities
      are blocked by the gibberellin-inactivated repressor RGA. In addition, a
      tripartite HLH/bHLH module feedback regulates PIFs and additional bHLH factors
      that interact with ARF6, and thereby modulates auxin sensitivity according to
      developmental and environmental cues. Our results demonstrate a central growth
      regulation circuit that integrates hormonal, environmental, and developmental
      controls of cell elongation in Arabidopsis hypocotyl. 

PMID- 24867226
TI  - Direct optical mapping of anisotropic stresses in nanowires using transverse
      optical phonon splitting.
AB  - Strain engineering is ubiquitous in the design and fabrication of innovative,
      high-performance electronic, optoelectronic, and photovoltaic devices. The
      increasing importance of strain-engineered nanoscale materials has raised
      significant challenges at both fabrication and characterization levels. Raman
      scattering spectroscopy (RSS) is one of the most straightforward techniques that
      have been broadly utilized to estimate the strain in semiconductors. However,
      this technique is incapable of measuring the individual components of stress,
      thus only providing the average values of the in-plane strain. This inherit
      limitation severely diminishes the importance of RSS analysis and makes it
      ineffective in the predominant case of nanostructures and devices with a
      nonuniform distribution of strain. Herein, we circumvent this major limitation
      and demonstrate for the first time the application of RSS to simultaneously probe
      the two local stress in-plane components in individual ultrathin silicon
      nanowires based on the imaging of the splitting of the two forbidden transverse
      optical phonons. 

PMID- 24867227
TI  - Reappraising the findings of the global burden of mental and substance use
      disorders.

PMID- 24867228
TI  - Short-time dynamic signature of the liquid-crystal-glass transition in a
      suspension of charged spherical colloids.
AB  - In this paper, the dynamic transition of the liquid-crystal-glass transition is
      investigated by dynamic light scattering, DLS. From the intensity autocorrelation
      function, g2(q, t), the short-time dynamic function, D(q), has been determined at
      different concentrations in both the crystal and glass regions. From D(q), the
      short-time self-diffusion, ds, was determined. ds speeds up in the crystal state
      but has very similar characteristics in the liquid and the glass region. The
      general model in which the colloidal crystallization transition in a spherical
      colloidal system is driven by an increase in local entropy is also verified by
      relating ds to the local excess entropy. Experimentally determined structure
      factors, S(q), are also discussed, and we show the similarity between the glass
      and the liquid. This investigation shows that the liquid-crystal transition can
      be identified in addition to the appearance of Bragg peaks with a short-time
      dynamic transition while no sharp transition in the short-time dynamics or S(q)
      can be found between the glass and the liquid. 

PMID- 24867225
TI  - Managing the skin toxicities from new melanoma drugs.
AB  - Patients treated with ipilimumab or targeted inhibitors of the RAF-MEK-ERK
      pathway (vemurafenib, dabrafenib, and trametinib) for advanced cutaneous melanoma
      often experience drug-related skin toxicities denoted as dermatologic adverse
      events (DAEs). Although rarely life-threatening, DAEs may emerge dramatically and
      potentially compromise oncologic therapy if not managed in a timely and effective
      manner. Early recognition of DAEs is critical to providing optimal skin care and
      prompt consultation with a dermatologist should be obtained when a diagnosis is
      unclear. The expanding utilization of new melanoma drugs compels physicians to
      maintain a watchful eye for both known and novel DAEs and to adopt a low
      threshold to biopsy worrisome skin findings. Numerous therapeutic options are
      available to manage DAEs including topical and systemic agents as well as
      surgical and destructive modalities. Applying such methods improves overall
      patient care and optimizes the effectiveness of new therapies for advanced
      cutaneous melanoma.

PMID- 24867229
TI  - One-pot synthesis and electrocatalytic properties of Pd@Pt core-shell
      nanocrystals with tailored morphologies.
AB  - Pd@Pt core-shell nanocrystals consisting of well-defined Pd nanocube cores and
      dendritic Pt shells were prepared by a new facile aqueous one-pot synthetic
      method. The prepared Pd@Pt nanocrystals exhibited efficient catalytic activity
      and stability toward methanol electrooxidation, and their catalytic function was
      highly dependent on their Pt shell thickness due to the different synergism
      between Pt and Pd. 

PMID- 24867230
TI  - Comparison of the efficacy of a novel sustained release clotrimazole varnish and
      clotrimazole troches for the treatment of oral candidiasis.
AB  - OBJECTIVES: Candida albicans is a common fungal infection and is commensal in 40
      65 % of healthy adults. The development and pharmacokinetics of a novel sustained
      release clotrimazole varnish (Clot-SRV) for topical oral use have been reported.
      The aim of this study was to compare the efficacy of this varnish with
      clotrimazole troche treatment of oral candidiasis. MATERIALS AND METHODS: Of the
      12 patients with denture stomatitis treated for 14 days, six used Clot-SRV (study
      group) and six clotrimazole troches (control). The patients were instructed to
      use Clot-SRV (50 mg of clotrimazole) once a day, and the control group was
      instructed to use five troches of 10 mg clotrimazole/day. Microbiological samples
      were obtained from saliva, buccal mucosa, palate, and denture. The degree of
      erythema was recorded at three time points, and subjective opinions noted using a
      questionnaire. RESULTS: At the end of the study, the control group had relatively
      more cases of erythema on all examined surfaces; patients who applied the Clot
      SRV had significantly lower levels of candida on the denture surfaces and in
      saliva, and had better compliance to the medication. CONCLUSIONS: The novel
      clotrimazole sustained release varnish may be an important part of a new protocol
      for oral candidiasis, with improved clinical outcomes.

PMID- 24867231
TI  - Damage of lithium-disilicate all-ceramic restorations by an experimental self
      adhesive resin cement used as core build-ups.
AB  - OBJECTIVES: This in vitro study aimed to predict the potential of fracture
      initiation after long-term incubation (LTI) of lithium-disilicate restorations
      due to a hygroscopic expansion of self-adhesive resin cement (SARC) used as core
      build-up material. METHODS: Human maxillary central incisors were divided into
      four groups (n = 10). Teeth were endodontically treated and decoronated.
      Specimens were restored in a one-stage post-and-core procedure using experimental
      dual-curing SARC. Three application protocols to build up the core were compared
      as follows: I, auto-polymerisation; II, dual curing including 40 s light
      initiated polymerisation; and III, an open matrix technique in a dual-curing
      mode. In group IV, a chemical-curing composite core build-up material served as
      control. For all specimens, a 2-mm ferrule design was ensured. Full anatomic
      lithium-disilicate crowns were adhesively luted. One-year LTI in 0.5 % chloramine
      solution at 37  degrees C was performed. Restorations were examined after 3, 6, 9
      and 12 month of storage. Survival rates were calculated using log-rank statistics
      (p = 0.05). RESULTS: Fifty per cent of lithium-disilicate crowns of groups I and
      II showed visible crack propagation after 9 months of incubation, while one crown
      failed in group III. No failure was observed in group IV. The survival rates
      differed significantly (p = 0.017). CONCLUSION: SARC used to build up the core of
      severely damaged endodontically treated teeth does have the potential to cause
      fracture of lithium-disilicate crown restorations. CLINICAL RELEVANCE:
      Hygroscopic expansion of self-adhesive resin cements used as a core build-up
      material might have an adverse impact on longevity of glass-ceramic crowns.

PMID- 24867232
TI  - Delineation of solution burst-phase protein folding events by encapsulating the
      proteins in silica gels.
AB  - Many studies have shown that during the early stages of the folding of a protein,
      chain collapse and secondary structure formation lead to a partially folded
      intermediate. Thus, direct observation of these early folding events is crucial
      if we are to understand protein-folding mechanisms. Notably, these events usually
      manifest as the initial unresolvable signals, denoted the burst phase, when
      monitored during conventional mixing experiments. However, folding events can be
      substantially slowed by first trapping a protein within a silica gel with a large
      water content, in which the trapped native state retains its solution
      conformation. In this study, we monitored the early folding events involving
      secondary structure formation of five globular proteins, horse heart cytochrome
      c, equine beta-lactoglobulin, human tear lipocalin, bovine alpha-lactalbumin, and
      hen egg lysozyme, in silica gels containing 80% (w/w) water by CD spectroscopy.
      The folding rates decreased for each of the proteins, which allowed for direct
      observation of the initial folding transitions, equivalent to the solution burst
      phase. The formation of each initial intermediate state exhibited single
      exponential kinetics and Arrhenius activation energies of 14-31 kJ/mol.

PMID- 24867233
TI  - Neuregulin-1 protects myocardial cells against H2 O2 -induced apoptosis by
      regulating endoplasmic reticulum stress.
AB  - Neuregulin-1 (NRG-1) is a stress-mediated growth factor secreted by
      cardiovascular endothelial cells and provides the protection to myocardial cells,
      but the underlying mechanisms are not fully understood. This study aimed to
      demonstrate that NRG-1 protects myocardial cells exposed to oxidative damage by
      regulating endoplasmic reticulum (ER) stress. Neonatal rat cardiac myocytes
      (NRCMs) were isolated and treated with H2 O2 as a cellular model of ER stress.
      NRCMs were pretreated with different concentrations of NRG-1. We found that NRG-1
      increased the viability and reduced the apoptosis of NRCMs treated by H2 O2 .
      Moreover, NRG-1 reduced lactate dehydrogenase level, increased superoxide
      dismutase activity and decreased malondialdehyde content in NRCMs treated by H2
      O2 . Finally, we demonstrated that NRG-1 alleviated ER stress and decreased CHOP
      and GRP78 protein levels in NRCMs treated by H2 O2 . Taken together, these data
      indicate that NRG-1 relieves oxidative and ER stress in NRCMs and suggest that
      NRG-1 is a promising agent for cardioprotection.

PMID- 24867234
TI  - Mild hydrothermal crystal growth, structure, and magnetic properties of ternary
      U(IV) containing fluorides: LiUF5, KU2F9, K7U6F31, RbUF5, RbU2F9, and RbU3F13.
AB  - Single crystals of several ternary alkali uranium fluorides, LiUF5, KU2F9,
      K7U6F31, RbUF5, RbU2F9, and RbU3F13, have been obtained in a mild hydrothermal
      process using UO2(CH3CO2)2(H2O)2 as the uranium source. Their crystal structures
      were determined by single crystal X-ray diffraction. The uranium in the starting
      reagent was successfully reduced from U(6+) to U(4+) in a dilute hydrofluoric
      acid environment, aided by the presence of a copper salt. All materials exhibit
      highly complex crystal structures that range from two-dimensional to three
      dimensional. The U(4+) cations are found in high (UF8 and UF9) coordination
      environments. The magnetic susceptibility measurements yielded effective magnetic
      moments of 3.01-3.83 MUB for the U(4+) cations. The temperature dependent
      magnetic susceptibility measurements confirmed that the U(4+) cation exhibits a
      nonmagnetic singlet ground state at low temperatures. No long-range magnetic
      order was observed for any of the above compositions down to 2 K. Optical and
      thermal behaviors of the fluorides were also investigated. 

PMID- 24867237
TI  - Erratum to: Efficacy of Liraglutide in a Real-Life Cohort.

PMID- 24867235
TI  - Fucose-specific DC-SIGN signalling directs T helper cell type-2 responses via
      IKKepsilon- and CYLD-dependent Bcl3 activation.
AB  - Carbohydrate-specific signalling through DC-SIGN provides dendritic cells with
      plasticity to tailor immunity to the nature of invading microbes. Here we
      demonstrate that recognition of fucose-expressing extracellular pathogens like
      Schistosoma mansoni and Helicobacter pylori by DC-SIGN favors T helper cell type
      2 (TH2) responses via activation of atypical NF-kappaB family member Bcl3.
      Crosstalk between TLR and DC-SIGN signalling results in TLR-induced MK2-mediated
      phosphorylation of LSP1, associated with DC-SIGN, upon fucose binding.
      Subsequently, IKKepsilon and CYLD are recruited to phosphorylated LSP1.
      IKKepsilon activation is pivotal for suppression of CYLD deubiquitinase activity
      and subsequent nuclear translocation of ubiquitinated Bcl3. Bcl3 activation
      represses TLR-induced proinflammatory cytokine expression, while enhancing
      interleukin-10 (IL-10) and TH2-attracting chemokine expression, shifting TH
      differentiation from TH1 to TH2 polarization. Thus, DC-SIGN directs adaptive TH2
      immunity to fucose-expressing pathogens via an IKKepsilon-CYLD-dependent
      signalling pathway leading to Bcl3 activation, which might be targeted in
      vaccination strategies or to prevent aberrant inflammation and allergy. 

PMID- 24867238
TI  - [Farewell from the Board of GST].

PMID- 24867236
TI  - Cep126 is required for pericentriolar satellite localisation to the centrosome
      and for primary cilium formation.
AB  - BACKGROUND INFORMATION: The centrosome is the primary microtubule-organising
      centre of animal cells and it has crucial roles in several fundamental cellular
      functions, including cell division, cell polarity, and intracellular transport.
      The mechanisms responsible for this are not completely understood. RESULTS: The
      poorly characterised protein CEP126 localises to the centrosome, pericentriolar
      satellites and the base of the primary cilium. Suppression of CEP126 expression
      results in dispersion of the pericentriolar satellites and disruption of the
      radial organisation of the microtubules, and induces disorganisation of the
      mitotic spindle. Moreover, CEP126 depletion or the transfection of a CEP126
      truncation mutant in hTERT-RPE-1 and IMCD3 cells impairs the formation of the
      primary cilium. CONCLUSIONS: We propose that CEP126 is a regulator of microtubule
      organisation at the centrosome that acts through modulation of the transport of
      pericentriolar satellites, and consequently, of the organisation of cell
      structure.

PMID- 24867239
TI  - [Inheritance and disease in the pig: possibilities of use for breeding].
AB  - Single-locus disorders in domesticated animals were among the first Mendelian
      traits to be documented, and to be included in early linkage maps. The use of
      linkage maps and comparative genomics has been essential to the identification of
      the causative genes for disorders. A DNA marker for selection of resistance to
      F18+ E. coli in the pig is available since several years. The use of this marker
      decreases mortality due to post-weaning diarrhoea and/or oedema disease. For more
      than 100 disorders the molecular lesion has been identified and hence for which a
      DNA test is available. However, for most diseases such as Porcine Reproductive
      and Respiratory Syndrome (PRRS) and Porcine Circovirus Associated Diseases
      (PCVAD), resistance is a complex and polygenic trait. Novel technologies such as
      gene microarrays and advanced bioinformatics are being used to analyse health
      data. Lagging behind, however, is availability of large DNA data sets from
      pedigreed populations with accurately measured health phenotypes that are needed
      to identify associations between markers and health traits. As the pig genome is
      sequenced to a great extent and ten thousands of markers can be analysed at a
      reasonable price, genomic selection for health traits is possible. 

PMID- 24867240
TI  - [Prevalence of pectinate ligament dysplasia in golden retrievers in Switzerland].
AB  - The prevalence of pectinate ligament dysplasia was evaluated in a prospective
      multi-center examination of randomly selected Golden retrievers of variable sex
      and age. The examinations were carried out by qualified veterinary
      ophthalmologists between May 1 and May 31, 2013. A total of 92 dogs (29 male and
      62 female dogs) were examined. The dogs were between 6 months and 14 years old
      (4.53 +/- 3.02 years). Gonioscopy was performed under topical anesthesia using a
      Koeppe lens and a hand-held slit lamp with >= 10-x magnification. Four quadrants
      (dorsal, lateral, medial, ventral) were examined in each eye. For each quadrant a
      score between 3 (normal) and 0 (grossly abnormal) was assigned. The average total
      score for all quadrants was 2.14 +/- 0.95. The width of the drainage angle W was
      2.29 +/- 0.88, while the score for mesodermal dysplasia MD was 1.98 +/- 0.98.
      There was no significant difference between left and right eyes, however, a
      significant difference was found between female and male dogs, as well as between
      young dogs and older dogs. The width of the drainage angle decreased with age and
      the degree of mesodermal dysplasia increased. Female dogs had lower total scores
      compared to male dogs and the ventral and lateral quadrants had significantly
      lower scores than the other quadrants. In conclusion, 52/92 (56.5 %) showed signs
      of Pectinate ligament dysplasia and would have to be excluded from a breeding
      program according to the guidelines of the European College of Veterinary
      Ophthalmologists. 

PMID- 24867241
TI  - [Endoscopic reposition of pylorogastric intussusception in a dog].
AB  - A 7 month old West Highland White Terrier was presented with anorexia and vomitus
      since 4 days. On physical examination the dog was depressed, febrile and showed
      abdominal pain. During abdominal ultrasonographic examination a pylorogastric
      intussusception was suspected and this was confirmed subsequently by gastroscopy.
      The invaginated pylorus could be repositioned without complications using the
      endoscope. The dog recovered completely and without recurrence. A pylorogastric
      intussusception is a rarely diagnosed cause of an acute abdomen that can be
      resolved with a minimal invasive procedure. 

PMID- 24867242
TI  - Ocular signs, diagnosis and long-term treatment with allopurinol in a cat with
      leishmaniasis.
AB  - A case of leishmaniasis with predominantly ocular signs in a cat living in
      Switzerland and it's treatment is reported. The cat was imported from Spain 4
      years earlier and was initially presented with chronic uveitis. Laboratory test
      results were negative for feline immunodeficiency virus (FIV), feline infectious
      peritonitis (FIP), feline leukaemia virus (FeLV) and Toxoplasma gondii, as well
      as for Bartonella haenselae and Leishmania spp. Twenty-one months later the cat
      was presented again because of development of keratitis and granulomatous
      blepharitis. Blood cell count revealed severe Pancytopenia; Cytology of fine
      needle aspirates of granulomatous lesions on both upper eyelids and of a corneal
      smear revealed intracytoplasmatic microorganisms. A preliminary diagnosis of
      leishmaniasis was supported by positive polymerase chain reaction from bone
      marrow and eyelid samples for Leishmania infantum DNA and by a high serum
      antibody titer for Leishmania spp. Treatment with Allopurinol (10 mg/kg, BID)
      orally led to rapid improvement of ocular signs, general condition and blood cell
      count with complete remission of lid and corneal lesions within 2 months of
      treatment. 

PMID- 24867243
TI  - [Infection with the capnophilic bacteria Enterococcus cecorum in broiler
      chickens].

PMID- 24867246
TI  - [Celebrating 200 years of GTT in Thurgau : Open house day on 26 April, 2014].

PMID- 24867247
TI  - [Traveling with your dog , cat and mouse ... ?].

PMID- 24867248
TI  - [The job of disclosure - what to consider, what is necessary?].

PMID- 24867249
TI  - Inhibition of protein phosphatase 2A enhances cytotoxicity and accessibility of
      chemotherapeutic drugs to hepatocellular carcinomas.
AB  - Hepatocellular carcinoma (HCC) is one of the most common and therapeutically
      challenging malignancies worldwide. For patients ineligible for "curative
      resection" or liver transplantation, chemotherapy is an important minimally
      effective option. Strategies for chemosensitization are urgently needed. Here, we
      report that LB-100, a serine/threonine protein phosphatase 2A (PP2A) inhibitor,
      enhances the cytotoxicity of chemotherapy for HCC in vitro and in vivo. We found
      that LB-100 significantly enhanced inhibition of HCC by doxorubicin and cisplatin
      in vitro and in vivo in a PP2A-dependent way, while having little inhibitory
      activity when used alone. LB-100 promoted vascular endothelial growth factor
      secretion and vasculogenic mimicry, associated with increased microvessel density
      and blood perfusion of tumor cell xenografts. LB-100 also enhanced paracellular
      endothelial permeability to Evans Blue dye and doxorubicin in vivo and in vitro,
      presumably by altering vascular endothelial-cadherin contact between cells.
      Changes in permeability and perfusion were accompanied by increased accumulation
      of doxorubicin in HCC xenografts but not in normal liver tissue. In conclusion,
      LB-100 enhances chemotherapy by interfering with DNA damage-induced defense
      mechanisms and by increasing angiogenesis and drug penetration into tumor cells.
      The induction of angiogenesis and vascular permeability of tumor xenografts by
      inhibition of PP2A may be a novel approach for enhancing the cytotoxic treatment
      of HCC and potentially other cancers.

PMID- 24867251
TI  - Synthetic polyamine BPA-C8 inhibits TGF-beta1-mediated conversion of human dermal
      fibroblast to myofibroblasts and establishment of galectin-1-rich extracellular
      matrix in vitro.
AB  - Cancer-associated fibroblasts (CAFs) play a role in the progression of malignant
      tumors. They are formed by conversion of fibroblasts to smooth muscle alpha-actin
      positive (SMA-positive) myofibroblasts. Polyamines are known to change the
      arrangement of the actin cytoskeleton by binding to the anionic actin. We tested
      the effect of the synthetic polyamine BPA-C8 on the transition of human dermal
      fibroblasts to myofibroblasts induced either by TGF-beta1 alone or by TGF-beta1
      together with adhesion/growth-regulatory galectin-1. Pre-existing CAFs,
      myofibroblasts from pancreatitis, and rat smooth muscle cells were also exposed
      to BPA-C8. BPA-C8 impaired myofibroblast formation from activated fibroblasts,
      but it had no effect on cells already expressing SMA. BPA-C8 also reduced the
      occurrence of an extracellular matrix around the activated fibroblasts. The
      reported data thus extend current insights into polyamine activity, adding
      interference with tumor progression to the tumor-promoting processes warranting
      study. 

PMID- 24867250
TI  - Mechanism and efficacy of sub-50-nm tenfibgen nanocapsules for cancer cell
      directed delivery of anti-CK2 RNAi to primary and metastatic squamous cell
      carcinoma.
AB  - Improved survival for patients with head and neck cancers (HNC) with recurrent
      and metastatic disease warrants that cancer therapy is specific, with protected
      delivery of the therapeutic agent to primary and metastatic cancer cells. A
      further objective should be that downregulation of the intracellular therapy
      target leads to cell death without compensation by an alternate pathway. To
      address these goals, we report the utilization of a sub-50-nm tenfibgen (s50-TBG)
      nanocapsule that delivers RNAi oligonucleotides directed against the essential
      survival signal protein kinase CK2 (RNAi-CK2) in a cancer cell-specific manner.
      We have evaluated mechanism and efficacy of using s50-TBG-RNAi-CK2 nanocapsules
      for therapy of primary and metastatic head and neck squamous cell carcinoma
      (HNSCC). s50-TBG nanocapsules enter cancer cells via the lipid raft/caveolar
      pathway and deliver their cargo (RNAi-CK2) preferentially to malignant but not
      normal tissues in mice. Our data suggest that RNAi-CK2, a unique single-stranded
      oligonucleotide, co-opts the argonaute 2/RNA-induced silencing complex pathway to
      target the CK2alphaalpha' mRNAs. s50-TBG-RNAi-CK2 inhibited cell growth
      corresponding with reduced CK2 expression in targeted tumor cells. Treatment of
      three xenograft HNSCC models showed that primary tumors and metastases responded
      to s50-TBG-RNAi-CK2 therapy, with tumor shrinkage and 6-month host survival that
      was achieved at relatively low doses of the therapeutic agent without any adverse
      toxic effect in normal tissues in the mice. We suggest that our nanocapsule
      technology and anti-CK2 targeting combine into a therapeutic modality with a
      potential of significant translational promise.

PMID- 24867252
TI  - Circulating cytokines and alarmins associated with placental inflammation in high
      risk pregnancies.
AB  - PROBLEM: Inflammation during pregnancy has devastating consequences for the
      placenta and fetus. These events are incompletely understood, thereby hampering
      screening and treatment. METHOD OF STUDY: The inflammatory profile of villous
      tissue was studied in pregnancies at high-risk of placental dysfunction and
      compared to uncomplicated pregnancies. The systemic inflammatory profile was
      assessed in matched maternal serum samples in cases of reduced fetal movements
      (RFM). RESULTS: Placentas from RFM pregnancies had a unique inflammatory profile
      characterized by increased interleukin (IL)-1 receptor antagonist and decreased
      IL-10 expression, concomitant with increased numbers of placental macrophages.
      This aberrant cytokine profile was evident in maternal serum in RFM, as were
      increased levels of alarmins (uric acid, HMGB1, cell-free fetal DNA). CONCLUSION:
      This distinct inflammatory profile at the maternal-fetal interface, mirrored in
      maternal serum, could represent biomarkers of placental inflammation and could
      offer novel therapeutic options to protect the placenta and fetus from an adverse
      maternal environment.

PMID- 24867254
TI  - Folic acid: a biopharmaceutical evaluation.
AB  - The aqueous solubility and drug product dissolution are important factors that
      determine the rate and extent of drug absorption from immediate release solid
      oral dosage forms. The aim of this article was to perform a folic acid
      biopharmaceutical study to evaluate the biowaiver of new products containing
      folic acid. We studied the solubility of its raw material and the dissolution
      profile of two commercially available products. Three different buffers (pH 1.2,
      4.5 and 6.8) were used as the media of the solubility and dissolution tests
      (apparatus II, at 50 rpm and 900 mL of medium volume). We found that folic acid
      solubility and its release from tablets are pH dependent. The dissolution
      profiles of both tablets were compared by dissolution efficiency (%), using t
      test or variance analysis (ANOVA). The dissolution profiles obtained for the two
      products at pH 1.2 medium were similar (p > 0.05), but they were dissimilar at pH
      4.5 and 6.8 (p < 0.05). Furthermore, we could observe differences between all the
      dissolution profiles of folic acid for each product at three different
      dissolution media used. The results showed that physicochemical characteristics
      of folic acid affect its dissolution and absorption making it difficult to take a
      decision on their biowaiver based on BCS. 

PMID- 24867253
TI  - Evidence for topographic guidance of dopaminergic axons by differential Netrin-1
      expression in the striatum.
AB  - There are two main subgroups of midbrain dopaminergic (DA) neurons: the more
      medially located ventral tegmental area (VTA) DA neurons, which have axons that
      innervate the ventral-lateral (VL) striatum, and the more laterally located
      substantia nigra (SN) DA neurons, which preferentially degenerate in Parkinson's
      disease (PD) and have axons that project to the dorsal-medial (DM) striatum. DA
      axonal projections in the striatum are not discretely localized and they arborize
      widely, however they do not stray from one zone to the other so that VTA axons
      remain in the VL zone and SN axons in the DM zone. Here we provide evidence that
      Netrin-1 acts in a novel fashion to topographically pattern midbrain DA axons
      into these two striatal zones by means of a gradient of Netrin-1 in the striatum
      and by differential attraction of the axons to Netrin-1. Midbrain DA neurons are
      attracted to the striatum in culture and this attraction is blocked by an anti
      DCC (Netrin receptor) antibody. Mechanistically, outgrowth of both VTA and SN DA
      axons is stimulated by Netrin-1, but the two populations of DA axons respond
      optimally to overlapping but distinct concentrations of Netrin-1, with SN axons
      preferring lower concentrations and VTA axons preferring higher concentrations.
      In vivo this differential preference is closely mirrored by differences in Netrin
      1 expression in their respective striatal target fields. In vivo in mice lacking
      Netrin-1, DA axons that reach the striatum fail to segregate into two terminal
      zones and to fully innervate the striatum. Our results reveal novel actions for
      Netrin-1 and provide evidence for a mechanism through which DA axons can
      selectively innervate one of two terminal zones in the striatum but have free
      reign to arborize widely within a terminal zone.

PMID- 24867255
TI  - Injection artefact displaying "sock" pattern on bone scan: "glove" sign
      equivalent resulting from bisphosphonate-(99mTc) injection in foot venous system.

PMID- 24867257
TI  - Nuclear medicine training and practice in the Czech Republic.
AB  - Nuclear medicine in the Czech Republic is a full specialty with an exclusive
      practice. Since the training program was organized and structured in recent
      years, residents have had access to the specialty of nuclear medicine, starting
      with a two-year general internship (in internal medicine or radiology). At
      present, nuclear medicine services are provided in 45 departments. In total, 119
      nuclear medicine specialists are currently registered. In order to obtain the
      title of Nuclear Medicine Specialist, five years of training are necessary; the
      first two years consist of a general internship in internal medicine or
      radiology. The remaining three years consist of training in the nuclear medicine
      specialty itself, but includes three months of practice in radiology. Twenty-one
      physicians are currently in nuclear medicine training and a mean of three
      specialists pass the final exam per year. The syllabus is very similar to that of
      the European Union of Medical Specialists (UEMS), namely concerning the minimum
      recommended numbers for diagnostic and therapeutic procedures. In principle, the
      Czech law requires continuous medical education for all practicing doctors. The
      Czech Medical Chamber has provided a continuing medical education (CME) system.
      Other national CMEs are not accepted in Czech Republic. 

PMID- 24867256
TI  - Differences in striatal dopamine transporter density between tremor dominant and
      non-tremor Parkinson's disease.
AB  - PURPOSE: Parkinson's disease (PD) can manifest with a tremor-dominant or a non
      tremor (akinetic-rigid) phenotype. Although the tremor-dominant subtype may show
      a better prognosis, there is limited information on the phenotypic differences
      regarding the level of striatal dopamine transmission. The present study
      investigated striatal dopamine transporter (DAT) binding characteristics in a
      large sample of patients with and without tremor. METHODS: [(123)I]FP-CIT SPECT
      scans of 231 patients with a clinical diagnosis of PD and abnormal FP-CIT binding
      (157 with tremor, 74 without tremor) and 230 control patients with normal FP-CIT
      binding (148 with tremor, 82 without tremor) were analysed using an automated
      region-of-interest analysis of the scans (BRASS). Specific striatal binding
      ratios were compared between phenotypes and groups using age, sex, and symptom
      duration, predominant side of symptoms, dopaminergic medications and scanner as
      covariates. RESULTS: Patients with PD had 28.1 - 65.0 % lower binding in all
      striatal regions compared to controls (p < 0.001). The mean FP-CIT caudate
      nucleus uptake and the left caudate nucleus uptake were higher in PD patients
      with tremor than in PD patients without tremor (mean 9.0 % higher, left 10.5 %
      higher; p < 0.05), whereas there were no differences between tremor and non
      tremor control patients. No significant effects of tremor on DAT binding were
      observed in the anterior or posterior putamen. CONCLUSION: The motor phenotype is
      associated with the extent of caudate dopamine terminal loss in PD, as dopamine
      function is relatively more preserved in tremor patients. Symptom type is related
      to caudate dopamine function only in association with Parkinsonian dopaminergic
      degeneration, not in intact dopamine systems in patients with non-PD tremor.

PMID- 24867259
TI  - Nutlin-3 induces BCL2A1 expression by activating ELK1 through the mitochondrial
      p53-ROS-ERK1/2 pathway.
AB  - Nutlin-3 which occupies the p53 binding pocket in HDM2, has been reported to
      activate apoptosis through both the transcriptional activity-dependent and 
      independent programs of p53. Transcription-independent apoptosis by nutlin-3 is
      triggered by p53 which is translocated to mitochondria. However, we previously
      demonstrated that the nutlin-3-induced mitochondrial translocation of p53
      stimulates ERK1/2 activation, an anti-apoptosis signal, via mitochondrial ROS
      generation. We report on how nutlin-3-stimulated ERK1/2 activity inhibits p53
      induced apoptosis. Among the anti-apoptotic BCL2 family proteins, BCL2A1
      expression was increased by nutlin-3 at both the mRNA and protein levels, and
      this increase was prevented by the inhibition of ERK1/2. TEMPO, a ROS scavenger,
      and PFT-MU , a blocker of the mitochondrial translocation of p53, also inhibited
      BCL2A1 expression as well as ERK1/2 phosphorylation. In addition, nutlin-3
      stimulated phosphorylation of ELK1, which was prevented by all compounds that
      inhibited nutlin-3-induced ERK1/2 such as U0126, PFT-MU and TEMPO. Moreover, an
      increase in BCL2A1 expression was weakened by the knockdown of ELK1. Finally,
      nutlin-3-induced apoptosis was found to be potentiated by the knockdown of
      BCL2A1, as demonstrated by an increase of in hypo-diploidic cells and Annexin V
      positive cells. Parallel to the increase in apoptotic cells, the knockdown of
      BCL2A1 augmented the cleavage of poly(ADP-ribose) polymerase-1. It is noteworthy
      that the augmented levels of apoptosis induced by the knockdown of BCL2A1 were
      comparable to those of apoptosis induced by U0126. Collectively, these results
      suggest that nutlin-3-activated ERK1/2 may stimulate the transcription of BCL2A1
      via the activation of ELK1, and BCL2A1 expression may contribute to the
      inhibitory effect of ERK1/2 on nutlin-3-induced apoptosis, thereby constituting a
      negative feedback loop of p53-induced apoptosis.

PMID- 24867258
TI  - Advantage of FMISO-PET over FDG-PET for predicting histological response to
      preoperative chemotherapy in patients with oral squamous cell carcinoma.
AB  - PURPOSE: Hypoxia, a prognostic factor in many types of cancer, can be detected by
      (18)F-fluoromisonidazole (FMISO) positron emission tomography (PET). It is
      unclear whether hypoxia reflects the response to chemotherapy in patients with
      oral squamous cell carcinoma (OSCC). The correlations of FMISO-PET and FDG-PET
      with histological response to preoperative chemotherapy were therefore assessed
      in patients with OSCC. METHODS: This study enrolled 22 patients with OSCC
      undergoing preoperative chemotherapy. The T-stages were T2 in 6 patients, T3 in
      3, and T4a in 13, and the N-stages were N0 in 14 patients, N1 in 3, and N2 in 5.
      Each patient was evaluated by both FMISO-PET and FDG-PET before surgery, and the
      maximum standardized uptake value (SUVmax) of FDG- and FMISO-PET and tumor-muscle
      ratio (TMR) of FMISO-PET were measured. The threshold for the hypoxic volume
      based on TMR was set at 1.25. The histological response to preoperative
      chemotherapy was evaluated using operative materials. RESULTS: FMISO-PET and FDG
      PET detected uptake by primary OSCCs in 15 (68%) and 21 (95%) patients,
      respectively, and median SUVmaxs of FMISO- and FDG-PET in the primary site were
      2.0 (range, 1.3-3.5) and 16.0 (range, 1.0-32.2), respectively. The median of
      FMISO TMR was 1.5 (range, 0.99-2.96). There were five cases whose FMISO TMR was
      less than 1.25. Histological evaluation showed good response to preoperative
      chemotherapy in 7 patients (32%) and poor response in 15 (68%). Good response was
      significantly more prevalent in patients with negative than positive FMISO uptake
      (P < 0.001) and without the hypoxic area evaluated by FMISO-PET TMR (P = 0.04),
      whereas FDG uptake was not significantly correlated with response to chemotherapy
      response. Multivariate logistic regression analysis showed that FMISO uptake was
      an independent significant predictor of response to preoperative chemotherapy (P
      = 0.03, odds ratio = 0.06, 95% confidence interval = 0.004-0.759). CONCLUSIONS:
      An advantage of FMISO-PET over FDG-PET for predicting histological response to
      preoperative chemotherapy in patients with OSCC was observed.

PMID- 24867260
TI  - Reference range of cerebrospinal fluid opening pressure in children: historical
      overview and current data.
AB  - The lumbar puncture and cerebrospinal fluid (CSF) opening pressure (OP) in
      children remains an essential diagnostic test for children with suspected
      elevated intracranial pressure. Recent prospective data have revised the
      normative CSF OP values and described how clinical variables such as age, depth
      of sedation, and obesity may influence the measurements. In addition, the new
      normative data are now reflected in revised diagnostic criteria for idiopathic
      intracranial hypertension/pseudotumor cerebri syndrome. This review highlights
      the recently published data and provides guidance on how it may impact clinical
      management. 

PMID- 24867262
TI  - Potential biomarkers and latent pathways for vasculitis based on latent pathway
      identification analysis.
AB  - AIM: We aimed in this study to identify the significant latent pathways and
      precise molecular mechanisms underlying the syndrome of vasculitis. METHODS:
      Agilent dual-channel data of peripheral blood mononuclear cells (PBMCs) from
      healthy controls and vasculitis patients were downloaded from EBI Array Express
      database. Differentially expressed genes (DEGs) between normal and vasculitis
      PBMCs samples were selected. Gene Ontology (GO) and Kyoto Encyclopedia of Genes
      and Genomes (KEGG) pathway analyses were carried out to identify significant
      biological processes and pathways. DEGs were matched to NetBox software database
      to obtain LINKER genes with statistical significance. Protein-protein interaction
      (PPI) network was constructed with LINKER genes and DEGs according to STRING
      database. Latent pathway identification analysis (LPIA) was used to identify the
      most significant interactions among different pathways involved by DEGs. RESULTS:
      A total of 266 DEGs were selected. GO and KEGG pathway analysis showed that the
      up-regulated genes were significantly enriched in defense and wounding response;
      the down-regulated genes were enriched in immune response. The modules analysis
      of PPI network suggested that ISG15 and IFIT3 were the potential biomarkers for
      vasculitis. The results of LPIA showed that NOD-like receptor signaling pathway
      and shigellosis related pathway were the two most significant latent pathway
      interactions for vasculitis. ISG15 and IFIT3 were the potential biomarkers for
      vasculitis identification. CONCLUSION: NOD-like receptor signaling pathway and
      shigellosis related pathway were the most significant latent pathway interactions
      for vasculitis. Moreover, LPIA was a useful method for revealing systemic
      biological pathways and cellular mechanisms of diseases.

PMID- 24867263
TI  - Aqueous and air-compatible fabrication of high-performance conductive textiles.
AB  - This paper describes a fully aqueous- and air-compatible chemical approach to
      preparing high-performance conductive textiles. In this method, the surfaces of
      textile materials are first modified with an aqueous solution of double-bond
      containing silane molecules to form a surface-anchoring layer for subsequent in
      situ free-radical polymerization of [2-(methacryloyloxy)ethyl]trimethylammonium
      chloride (METAC) in the air. Thin layers of poly-METAC (PMETAC) are therefore
      covalently grafted on top of the silane-modified textile surface. Cu- or Ni
      coated textiles are finally fabricated by electroless deposition (ELD) onto the
      PMETAC-modified textiles. Parameters including polymerization time, temperature,
      and ELD conditions are studied to optimize the whole fabrication process. The as
      made conductive textiles exhibit sheet resistance as low as 0.2 Omega sq(-1) ,
      which makes them highly suitable for use as conductive wires and interconnects in
      flexible and wearable electronic devices. More importantly, the chemical method
      is fully compatible with the conventional "pad-dry-cure" fabrication process in
      the textile manufacturing industry, thus indicating that it is very promising for
      high-throughput and roll-to-roll fabrication of high-performance metal-coated
      conductive textiles in the future. 

PMID- 24867264
TI  - On the optimization of operating conditions for Taylor dispersion analysis of
      mixtures.
AB  - In this work, we investigate the possibility of optimizing the operating
      conditions, namely mobilizing pressure, capillary length and capillary radius,
      for performing Taylor dispersion analysis on solutes having hydrodynamic
      diameter, 2Rh, between 1 and 100 nm. Optimizing Taylor dispersion analysis means
      finding the set of operating conditions that verify the conditions of validity of
      this method, and finding the most appropriate conditions that may enhance or
      maximize the separation performances. Our conclusion is that the performances of
      Taylor dispersion analysis are independent of the operating conditions, as far as
      the conditions of validity of the method are verified. The inequalities defining
      the set of acceptable operating conditions are given in this work as a function
      of the maximal relative error on the diffusion coefficient, D, fixed by the user.
      These inequalities define operating zones that were represented for three typical
      capillary diameters (25, 50 and 100 MUm). Within these zones, all experiments
      should lead to similar results on D (or Rh) and similar separation performances.
      It was concluded that assuming a 3% relative error on the determination of D, a
      60 cm * 50 MUm i.d. capillary can be used by default for performing TDA of
      analytes in the 1-100 nm diameter range with mobilizing pressure in the 50-100
      mbar range. 

PMID- 24867266
TI  - C-reactive protein and colorectal cancer mortality in U.S. adults.
AB  - BACKGROUND: Chronic inflammation has been associated with colorectal cancer.
      Prediagnostic levels of C-reactive protein (CRP), a highly sensitive marker of
      inflammation, have been weakly associated with increased colorectal cancer
      incidence, but few data are available examining its relationship with colorectal
      cancer mortality. METHODS: In the Third National Health and Nutrition Examination
      Survey (NHANES III), 65% of the 15,924 adult participants had CRP levels <=0.21
      mg/dL. Using this as the reference group, we calculated hazard ratios (HR) for
      higher CRP categories and colorectal cancer mortality, and compared them with HRs
      for other mortality causes. RESULTS: Over a median follow-up period of 14.2
      years, there were 92 deaths from colorectal cancer. Compared with the reference
      group, multivariable adjusted HRs for colorectal cancer mortality were 2.66 [95%
      confidence interval (CI), 1.36-5.20] for CRP levels 0.22-0.50 mg/dL; 3.40 (95%
      CI, 1.48-7.77) for levels 0.51-1.00 mg/dL; and 3.96 (95% CI, 1.64-9.52) for
      levels >1.00 mg/dL. Estimates for colorectal cancer mortality did not change
      appreciably after excluding deaths within the first 3 years or by limiting follow
      up to 5 or 10 years. CONCLUSIONS: In a large representative study of U.S. adults,
      we observed strong dose-response associations between CRP levels and colorectal
      cancer mortality. IMPACT: Further evaluation of CRP may help identify high-risk
      groups for colorectal cancer screening and those who might benefit most from
      prophylactic anti-inflammatory therapy.

PMID- 24867265
TI  - PLCE1 mRNA and protein expression and survival of patients with esophageal
      squamous cell carcinoma and gastric adenocarcinoma.
AB  - BACKGROUND: Germline genetic variants in PLCE1 (10q23) have demonstrated
      consistent associations with risk of esophageal squamous cell carcinoma (ESCC)
      and gastric cancer among Chinese. We evaluated PLCE1 mRNA and protein expression
      in paired tumor-normal tissues, and their relationship with survival. METHODS:
      PLCE1 mRNA was profiled using three probes in the Affymetrix GeneChip U133 for
      paired tumor-normal tissues of ESCC (n = 132), gastric cardia adenocarcinoma
      (GCA, n = 62), and gastric noncardia adenocarcinoma (GNCA, n = 72). We used
      immunohistochemistry to detect PLCE1 protein on slides from tissue microarrays in
      paired tumor-normal tissues of ESCC (n = 303), and tumors of GCA (n = 298) and
      GNCA (n = 124). RESULTS: Compared with normal tissues, PLCE1 mRNA expression was
      significantly reduced in ESCC tumors (P = 0.03, probe_205112_at), as well as in
      GCA and GNCA tumors (P < 0.0001, each probe). Protein expression was
      nonsignificantly reduced in ESCC tumors (P = 0.51). Increased tumor-normal mRNA
      fold change (probe_205112_at) was associated with longer survival in ESCC (9.6
      months for highest vs. lowest quartile; Ptrend = 0.02). Increased mRNA tumor
      normal fold change (probe_205111_at) was associated with longer survival for GCA
      (10.7 months for highest quartile; Ptrend = 0.04), but not for GNCA cases (P =
      0.72). Similar to mRNA, elevated tumor-normal fold change for protein in ESCC was
      also associated with improved survival (8.1 months for highest quartile; Ptrend =
      0.04). CONCLUSIONS: Dysregulated PLCE1 mRNA expression was observed for both ESCC
      (one probe only) and GCA tumors, and the altered PLCE1 expression seems to be
      associated with cancer prognosis. IMPACT: A potential role for PLCE1 in the early
      detection and/or therapy of ESCC and GCA warrants further investigation.

PMID- 24867267
TI  - Meta-Emotion Philosophy Among Asian Indian Immigrant Mothers in the United
      States.
AB  - We explored the meta-emotion philosophies of Indian immigrant mothers living in
      the Midwest region of the United States to expand the scarce literature on
      emotion socialization in diverse families. A total of 15 mothers of teen and
      preteen children participated in a meta-emotion interview, in which they were
      asked about their own and their children's experiences of anger, sadness, and
      fear. We analyzed interview responses through an open-ended phenomenological
      approach and found the following major themes: familial context of emotions,
      subtle communication of emotions, and an overarching philosophy centering on
      inevitability of negative emotions and the importance of moving on. Mothers
      differed in how well they believed that they could move on. Overall, the present
      findings demonstrate the role culture plays in emotional experiences of immigrant
      mothers and serve as a reminder that theories based on European American families
      might have limited applicability to other cultural and ethnic groups.

PMID- 24867268
TI  - Greater mortality and morbidity in extremely preterm infants fed a diet
      containing cow milk protein products.
AB  - BACKGROUND: Provision of human milk has important implications for the health and
      outcomes of extremely preterm (EP) infants. This study evaluated the effects of
      an exclusive human milk diet on the health of EP infants during their stay in the
      neonatal intensive care unit. SUBJECTS AND METHODS: EP infants <1,250 g birth
      weight received a diet consisting of either human milk fortified with a human
      milk protein-based fortifier (HM) (n=167) or a diet containing variable amounts
      of milk containing cow milk-based protein (CM) (n=93). Principal outcomes were
      mortality, necrotizing enterocolitis (NEC), growth, and duration of parenteral
      nutrition (PN). RESULTS: Mortality (2% versus 8%, p=0.004) and NEC (5% versus
      17%, p=0.002) differed significantly between the HM and CM groups, respectively.
      For every 10% increase in the volume of milk containing CM, the risk of sepsis
      increased by 17.9% (p<0.001). Growth rates were similar between groups. The
      duration of PN was 8 days less in the subgroup of infants receiving a diet
      containing <10% CM versus >=10% CM (p<0.02). CONCLUSIONS: An exclusive human milk
      diet, devoid of CM-containing products, was associated with lower mortality and
      morbidity in EP infants without compromising growth and should be considered as
      an approach to nutritional care of these infants.

PMID- 24867269
TI  - Excited state proton transfer in the lysosome of live lung cells: normal and
      cancer cells.
AB  - Dynamics of excited state proton transfer (ESPT) in the lysosome region of live
      lung cells (normal and cancer) is studied by picosecond time-resolved confocal
      microscopy. For this, we used a fluorescent probe, pyranine (8-hydroxy-pyrene
      1,3,6-trisulfonate, HPTS). From the colocalization of HPTS with a lysotracker dye
      (lysotracker yellow), we confirmed that HPTS resides in the lysosome for both of
      the cells. The diffusion coefficient (Dt) in the lysosome region was obtained
      from fluorescence correlation spectroscopy (FCS). From Dt, the viscosity of
      lysosome is estimated to be ~40 and ~30 cP in the cancer and normal cells,
      respectively. The rate constants of the elementary steps of ESPT in a normal lung
      cell (WI38) are compared with those in a lung cancer cell (A549). It is observed
      that the time constant of the initial proton transfer process in a normal cell
      (tau(PT) = 40 ps) is similar to that in a cancer cell. The recombination of the
      geminate ion pair is slightly faster (tau(rec) = 25 ps) in the normal cell than
      that (tau(rec) = 30 ps) in a cancer cell. The time constant of the dissociation
      (tau(diss)) of the geminate ion pair for the cancer cell (tau(diss) = 80 ps) is
      1.5 times faster compared to that (tau(diss) = 120 ps) in a normal cell.

PMID- 24867271
TI  - Molecular mechanisms of liver injury: apoptosis or necrosis.
AB  - Hepatic apoptosis is thought of as a prevalent mechanism in most forms of liver
      injury. However, the role of hepatic apoptosis is often intermixed with the
      cellular necrosis. It remains unknown how apoptosis is relevant to the
      progression of the liver injury. This review summarizes the characteristics of
      both hepatic apoptosis and necrosis in pathogenesis of liver diseases. Apoptosis
      and necrosis represent alternative outcomes of different etiology during liver
      injury. Apoptosis is a main mode of cell death in chronic viral hepatitis, but is
      intermingled with necrosis in cholestatic livers. Necrosis is the principal type
      of liver cell killing in acetaminophen-induced hepatotoxicity. Anti-apoptosis as
      a strategy is beneficial to liver repair response. Therapeutic options of liver
      disease depend on the understanding toward pathogenic mechanisms of different
      etiology. 

PMID- 24867270
TI  - C-reactive protein and coagulation studies in secondary post-tonsillectomy
      haemorrhage--need for routine testing? Our experience in 93 patients.

PMID- 24867272
TI  - Retained fetal adrenal cortex in a cynomolgus macaque (Macaca fascicularis).
AB  - An incidental, bilateral, retained fetal adrenal cortex was detected in a male
      cynomolgus macaque (age, approximately 2.4 y) used in a 4-week toxicology study.
      Microscopic examination of the adrenal gland cortex zone revealed the presence of
      additional solid sheets and columns of cells supported by vascular capillary bed
      and composed of large polyhedral cells with abundant eosinophilic, slightly
      finely vacuolated cytoplasm that surrounded the entire circumference of the
      medulla. Nuclei were vesicular, round to oval with prominent small nucleoli.
      There was no evidence for inflammation or cellular degeneration. Based on the
      microscopic examination, a diagnosis of retained fetal cortex of the adrenal
      gland was made. This morphologic change resembles fetal cortex in human infants.
      To our knowledge, this case description is the first report of a cynomolgus
      macaque with the rare entity of retained fetal cortex, which should not be
      misinterpreted as a test article-related change. 

PMID- 24867273
TI  - Experience with examination of the spinal cord and peripheral nervous system
      (PNS) in mice: A brief overview.
AB  - The representative areas for examination of the mouse peripheral nervous system
      are the spinal cord, containing central components of the peripheral nervous
      system that needs to be examined at least at cervical and lumbar level, the
      sciatic and the tibial nerve. Skeletal muscle samples should include the soleus
      muscle and the quadriceps femoris or long digital extensor, as well as the medial
      gastrocnemius. Examination can be extended to the thoracic spinal cord, lumbar
      dorsal root ganglia and spinal nerve roots, as well as the plantar nerve, and
      other areas of interest. Perfusion fixation is considered optimal for the nervous
      system; however, immersion fixation allows producing microscopic sections of
      excellent quality as well. Paraffin-embedded, hematoxylin and eosin-stained
      sections can be made from all areas, save for small nerves such as the tibial or
      plantar nerve, which are examined with advantage in hard plastic sections. It is
      possible to produce hard plastic sections also of the vertebral column, including
      the spinal cord, dorsal root ganglia and nerve roots. For special investigations,
      mice can be fixed in toto, decalcified, embedded and sectioned to reveal the
      areas of interest. In the mouse peripheral nerves, myelination progresses until
      the adult age. In aging peripheral nerves there is axonal atrophy, degeneration,
      nerve fiber loss, increase of collagen and sporadic demyelination, especially
      radiculoneuropathy. The dorsal root ganglia of untreated control animals show
      frequent cytoplasmic vacuolation. Axonal degeneration is distally, primary
      demyelination proximally accentuated. Mouse is not very sensitive to peripheral
      neurotoxicity: to induce toxic peripheral neuropathy mostly parenteral
      administration and/or newborn animals are used. Naturally occurring infection
      affecting the spinal cord and peripheral nerves is Theiler's encephalomyelitis
      virus inducing acute poliomyelitis or chronic demyelination. Any experimental
      results are to be assessed taking into account spontaneous, age-related,
      background changes. 

PMID- 24867274
TI  - Environmental determinants of the spatial distribution of Trichinella britovi and
      Trichinella spiralis in Hungary.
AB  - Trichinella spiralis and Trichinella britovi are the two most common species of
      the genus Trichinella persisting in the European wildlife. To investigate the
      spatial distribution of these Trichinella spp. and the factors influencing their
      circulation in Hungary, 3304 red foxes (Vulpes vulpes) and 0.29 million wild
      boars (Sus scrofa) were tested for Trichinella sp. infection in Hungary from 2006
      to 2013. Trichinella spp. larvae from 68 (2.06%) foxes and 44 (0.015%) wild boars
      were identified by a multiplex PCR as T. britovi or T. spiralis. The locality of
      origin of foxes and wild boars were recorded in a geographic information system
      database. There was no correlation between environmental parameters in the home
      range of foxes and wild boars and the T. spiralis larval counts, but there was a
      positive correlation between the boundary zone of Hungary and T. spiralis
      infection (P<0.0001; odds ratio: 24.1). These results indicate that the
      distribution of T. spiralis in the Hungarian wildlife is determined by the
      transborder transmission of the parasite from the surrounding endemic countries.
      Multiple regression analysis was performed with environmental parameter values
      and T. britovi larval counts. Based on the statistical analysis, non-agricultural
      areas (forests, scrubs, herbaceous vegetation and pastures) and the mean annual
      temperature (P<0.0001; odds ratios: 9.53 and 0.61) were the major determinants of
      the spatial distribution of T. britovi in Hungary. The positive relationship with
      non-agricultural areas can be explained by the generalist feeding behaviour
      including scavenging of foxes in these areas. The negative relationship with the
      mean annual temperature can be attributed to the slower decomposition of wildlife
      carcasses favouring a longer survival of T. britovi larvae in the host carrion
      and to the increase of scavenging of foxes. 

PMID- 24867275
TI  - First report of cattle farms with gastrointestinal nematodes resistant to
      levamisole in Mexico.
AB  - The objectives of the present study were: (1) to report the percentage of cattle
      farms with gastrointestinal nematodes (GINs) resistant to levamisole in Veracruz,
      Mexico, (2) to identify the genera of GINs involved in resistance, and (3) to
      identify factors associated with these resistances. The faecal egg count
      reduction test (McMaster technique) was used to detect the presence of resistant
      GINs. A questionnaire was given to owners to understand the history of
      anthelmintic use. The percentage of cattle farms with GINs resistant to
      levamisole was 36.4% (4/11). The percentage of faecal egg count reduction on
      resistant farms was 91%, 82%, 42% and 88%. A similar number of cattle farms
      (4/11) were identified as potentially having levamisole resistance. Only three
      farms had GIN populations susceptible to levamisole. Cooperia spp. was the genus
      most commonly found to be resistant, followed by Haemonchus spp., Ostertagia spp.
      and Oesophagostomum spp. No factors were identified that influenced the presence
      of GIN resistance. However, there were identified inappropriate anthelmintic
      practices in cattle farms that should be improved. None of the farmers weighed
      their animals in order to dose them correctly with anthelmintics. Six cattle
      farms (54.5%) applied anthelmintics to new arriving animals. This is the first
      report of levamisole resistant GINs in Mexico. Improving the use of anthelmintics
      and measures of quarantine for infected cattle will help control the spread of
      resistance. 

PMID- 24867280
TI  - Losing lives to the peril of ragging.

PMID- 24867281
TI  - Candidate biomarkers of multiple system atrophy in cerebrospinal fluid.
AB  - Multiple system atrophy (MSA) is a neurodegenerative disease that presents as an
      autonomic dysfunction in combination with varying degrees of parkinsonism and
      cerebellar ataxia. It comprises a pathologically widespread neuronal loss
      accompanied by gliosis in the basal ganglia, cerebellum, pons, inferior olivary
      nuclei, and spinal cord. As a rapidly progressive disorder, MSA develops with
      autonomic dysfunction and mobility problems in several years. These autonomic and
      motor function impairments severely disrupt the patients' daily lives. Currently,
      the therapeutic management of this disease is only symptomatic. An early and
      accurate diagnosis is helpful not only in the clinical field but also in the
      research for new therapies. The biomarkers in cerebrospinal fluid (CSF) and serum
      facilitate the differential diagnosis of MSA when the disease is difficult to
      recognize based on the clinical features or even presymptomatic. This review will
      summarize the biomarkers present in CSF that are potential candidates to
      accurately differentiate MSA from other similar neurodegenerative disorders.

PMID- 24867282
TI  - Computational approaches to the design of novel 5-HT6 R ligands.
AB  - 5-Hydroxytryptamine (5-HT, serotonin) subtype 6 receptor (5-HT6 receptor, 5-HT6
      R) belongs to a 5-HT subclass of a relatively wide G protein-coupled receptor
      (GPCR) family. Accumulated biological data indicate that 5-HT6 R antagonists and
      agonists have a great potential for the treatment of neuropathological disorders,
      such as Parkinson's disease, Alzheimer's disease, and schizophrenia. A number of
      painstaking efforts have been made toward the design of novel 5-HT6 R ligands;
      however, there are still no drugs that successfully passed all the clinical
      trials and entered the market, except for several multimodal ligands. Novel
      active molecules are strongly needed to progress this development forward. The in
      silico drug design has some benefits compared with the other rough approaches in
      terms of thoroughness and predictive accuracy; therefore, it can be effectively
      used as a solid foundation for the design of novel 5-HT6 R ligands with high
      potency and selectivity. Here, we provide an overview of the reported
      computational approaches to the design of novel 5-HT6 R ligands.

PMID- 24867284
TI  - Investigating the performance of AIC in selecting phylogenetic models.
AB  - The popular likelihood-based model selection criterion, Akaike's Information
      Criterion (AIC), is a breakthrough mathematical result derived from information
      theory. AIC is an approximation to Kullback-Leibler (KL) divergence with the
      derivation relying on the assumption that the likelihood function has finite
      second derivatives. However, for phylogenetic estimation, given that tree space
      is discrete with respect to tree topology, the assumption of a continuous
      likelihood function with finite second derivatives is violated. In this paper, we
      investigate the relationship between the expected log likelihood of a candidate
      model, and the expected KL divergence in the context of phylogenetic tree
      estimation. We find that given the tree topology, AIC is an unbiased estimator of
      the expected KL divergence. However, when the tree topology is unknown, AIC tends
      to underestimate the expected KL divergence for phylogenetic models. Simulation
      results suggest that the degree of underestimation varies across phylogenetic
      models so that even for large sample sizes, the bias of AIC can result in
      selecting a wrong model. As the choice of phylogenetic models is essential for
      statistical phylogenetic inference, it is important to improve the accuracy of
      model selection criteria in the context of phylogenetics.

PMID- 24867285
TI  - Detoxification of Echis ocellatus venom-induced toxicity by Annona senegalensis
      Pers.
AB  - Different fractions (I-V) of the methanolic leaf extracts of Annona senegalensis
      were assessed for their anti-snake venom activities. Fractions III neutralized
      lethal toxicity induced by Echis ocellatus venom and manifested the same potency
      as the crude extracts against the venom. The anti-snake venom activity of
      fraction III was clearly shown by the complete abrogation of venom-induced
      haemorrhage and the 75% record of surviving mice which were injected with a pre
      incubate of venom and extract in the ratio 1:30 w/w after a 24 h. Also, fraction
      III exhibited a weak inhibitory effect on fibrinogen clotting activity of this
      venom. The key phytochemicals mediating the activity of this fraction are
      flavonoids and tannins. The detoxification of this venom by fraction III and the
      possible mode of action in the pathology of snake envenoming is discussed in this
      report.

PMID- 24867286
TI  - Lateral solid-phase epitaxy of oxide thin films on glass substrate seeded with
      oxide nanosheets.
AB  - We developed a technique to fabricate oxide thin films with uniaxially controlled
      crystallographic orientation and lateral size of more than micrometers on
      amorphous substrates. This technique is lateral solid-phase epitaxy, where
      epitaxial crystallization of amorphous precursor is seeded with ultrathin oxide
      nanosheets sparsely (~10% coverage) deposited on the substrate. Transparent
      conducting Nb-doped anatase TiO2 thin films were fabricated on glass substrates
      by this technique. Perfect (001) orientation and large grains with lateral sizes
      up to 10 MUm were confirmed by X-ray diffraction, atomic force microscopy, and
      electron beam backscattering diffraction measurements. As a consequence of these
      features, the obtained film exhibited excellent electrical transport properties
      comparable to those of epitaxial thin films on single-crystalline substrates.
      This technique is a versatile method for fabricating high-quality oxide thin
      films other than anatase TiO2 and would increase the possible applications of
      oxide-based thin film devices. 

PMID- 24867287
TI  - New clues to the molecular pathogenesis of Burkitt lymphoma revealed through next
      generation sequencing.
AB  - PURPOSE OF REVIEW: Burkitt lymphoma is an important clinical and model disease
      arising from B cells. Burkitt lymphoma is characterized by translocation of the c
      MYC gene to an immunoglobulin enhancer region, resulting in enhanced cell
      proliferation and rapid tumor progression. The development of deep sequencing has
      widened the scope of genetic analysis to reveal the role of additional
      collaborating mutations in Burkitt lymphoma. In this review, we examine the role
      of additional genetic events that cooperate with MYC in Burkitt lymphoma
      pathogenesis. RECENT FINDINGS: Next-generation sequencing of Burkitt lymphoma has
      identified recurrent silencing mutations in ID3, a novel tumor suppressor gene.
      In addition, mutations in a number of genes including GNA13, TP53, and SMARCA4
      occur in Burkitt lymphoma. Copy number status has implicated recurrent
      aberrations including gains of 1q and 18q and deletion of 19p13. Additionally,
      microRNA and gene expression profiling has revealed unique transcriptome
      signatures in Burkitt lymphoma subgroups. SUMMARY: Analysis of genetic
      alterations in Burkitt lymphoma has yielded a better understanding of the
      pathogenesis of this disease. These observations could lead to more effective
      strategies for the diagnosis and treatment of Burkitt lymphoma.

PMID- 24867283
TI  - Pharmacogenetics in Jewish populations.
AB  - Spanning over 2000 years, the Jewish population has a long history of migration,
      population bottlenecks, expansions, and geographical isolation, which has
      resulted in a unique genetic architecture among the Jewish people. As such, many
      Mendelian disease genes and founder mutations for autosomal recessive diseases
      have been discovered in several Jewish groups, which have prompted recent genomic
      studies in the Jewish population on common disease susceptibility and other
      complex traits. Although few studies on the genetic determinants of drug response
      variability have been reported in the Jewish population, a number of unique
      pharmacogenetic variants have been discovered that are more common in Jewish
      populations than in other major racial groups. Notable examples identified in the
      Ashkenazi Jewish (AJ) population include the vitamin K epoxide reductase complex
      subunit 1 (VKORC1) c.106G>T (p.D36Y) variant associated with high warfarin dosing
      requirements and the recently reported cytochrome P450 2C19 (CYP2C19) allele,
      CYP2C19*4B, that harbors both loss-of-function [*4 (c.1A>G)] and increased
      function [*17 (c.-806C>T)] variants on the same haplotype. These data are
      encouraging in that like other ethnicities and subpopulations, the Jewish
      population likely harbors numerous pharmacogenetic variants that are uncommon or
      absent in other larger racial groups and ethnicities. In addition to unique
      variants, common multi-ethnic variants in key drug metabolism genes (e.g., ABCB1,
      CYP2C8, CYP2C9, CYP2C19, CYP2D6, NAT2) have also been detected in the AJ and
      other Jewish groups. This review aims to summarize the currently available
      pharmacogenetics literature and discuss future directions for related research
      with this unique population.

PMID- 24867288
TI  - The origin and targeting of mucosa-associated lymphoid tissue lymphomas.
AB  - PURPOSE OF REVIEW: Extranodal mucosa-associated lymphoid tissue (MALT lymphoma)
      is a distinct clinical-pathological entity that can be distinguished from other
      lymphomas by a number of unique features, including their location in various
      extranodal sites, being preceded by chronic inflammatory or infection processes;
      a characteristic histopathological picture; and the presence of exclusive
      chromosomal translocations which increase MALT1 proteolytic activity to promote
      constitutive NF-kappaB signaling and eventually drive lymphomagenesis. RECENT
      FINDINGS: This review explores the major molecular and cellular events that
      participate in MALT lymphoma pathogenesis, focusing on gastric MALT lymphoma as a
      model of chronic inflammation-induced tumor development. In addition, the pivotal
      roles of activated MALT1 protease, its substrate TNFAIP3/A20, and the MyD88
      adaptor protein in abnormally triggering downstream NF-kappaB pathway are
      overviewed. These new insights provide a mechanistic basis for using novel
      therapies targeting MALT1 protease or IRAK4 kinase activities. Finally, the
      putative cellular origin of MALT lymphomas is also discussed. SUMMARY: Over the
      last decade, unraveling the biological complexity of MALT lymphomas has shed
      light on the fundamental cellular and molecular aspects of the disease that are
      to be translated into clinical diagnostics and therapy.

PMID- 24867290
TI  - Quantitation of aflatoxins in walnut kernels by high-performance liquid
      chromatography with fluorescence detection.
AB  - A total of 85 walnut samples collected between October 2012 and April 2013 in
      different provinces of Turkey were analysed for the presence of aflatoxins (AFs).
      The method involved methanol-water extraction, clean-up with immunoaffinity
      columns and a sensitive high-performance liquid chromatography coupled with
      fluorescence detection after post-column derivatisation. The method was validated
      for selectivity, linearity, trueness, precision, limit of detection and limit of
      quantification (LOQ), which met the performance criteria as set by EC regulation
      No. 401/2006. LOQs were 0.07, 0.04, 0.09 and 0.05 ug kg(-1) for AFB1, AFB2, AFG1
      and AFG2, respectively. AFs were present in 9.4% of walnut samples (8/85) at
      total AFs levels ranging from 0.09 to 15.4 ug kg(-1). Only one of eight walnut
      samples exceeded the European Union limit of 2 and 4 ug kg(-1) for AFB1 and total
      AFs, respectively. 

PMID- 24867289
TI  - Role of Rho kinases in abnormal and normal hematopoiesis.
AB  - PURPOSE OF REVIEW: Rho kinases (ROCKs) are involved in regulating a variety of
      physiologic functions including cytoskeletal reorganization, migration, adhesion,
      survival and proliferation. They do so via activating several different
      downstream substrates such as myosin light chain phosphatase, LIM kinase and
      ezrin/radixin/moesin proteins. To date, most of the conclusions with regard to
      the function of ROCKs have involved the use of cell line models, pharmacologic
      inhibitors and dominant negative approaches. Importantly, the role of ROCK in
      hematopoiesis or leukemogenesis in the context of whole organism remains poorly
      understood. RECENT FINDINGS: Recent studies utilizing mice deficient in the
      expression of ROCK1 have begun to shed some light into the physiologic role(s) of
      ROCK in both normal and abnormal hematopoiesis. Findings, thus far, suggest that
      ROCK plays an essential role in regulating growth and survival in different
      hematopoietic lineages via distinct mechanisms, in part, by utilizing distinct
      downstream substrates including maintaining the activation of tumor-suppressor
      genes. SUMMARY: In blood cells, emerging data suggest that ROCK plays an
      essential role in negatively regulating inflammatory and erythropoietic stress
      and positively regulates the growth and survival of leukemic cells.

PMID- 24867291
TI  - Profiles of extracellular miRNAs in the aqueous humor of glaucoma patients
      assessed with a microarray system.
AB  - Aqueous humor (AH) is one of the body fluids in the eye, which is known to be
      related with various ocular diseases, but the complete RNAs characteristic of the
      AH in patients is not yet known. The aim of this study was, with a microarray
      analysis, to reveal the disease-related extracellular miRNAs profiles in
      individual patients AH. 100 MUl of AH was collected by anterior chamber
      paracentesis from 10 glaucoma, 5 cataract, and 5 epiretinal membrane patients.
      The extracted total RNAs were shorter than 200 nt, and their amount was 5.27 +/-
      0.41 ng in average. Among 530.5 +/- 44.6 miRNA types detected in each sample with
      a microarray detectable 2019 types of matured miRNAs, 172 miRNAs were detected in
      all 10 glaucoma or control patients. From the glaucoma group, 11 significantly up
      regulated and 18 significantly down-regulated miRNAs (P < 0.05 for both) were
      found to have areas under the curve better than 0.74 in a receiver operating
      characteristic analysis. They also formed a cluster composed only of glaucoma
      patients in a hierarchal cluster analysis. AH had a possibility of becoming a
      source of miRNA that can serve as a biomarker and a therapeutic target. 

PMID- 24867294
TI  - Insights into the association of Gla-rich protein and osteoarthritis, novel
      splice variants and gamma-carboxylation status.
AB  - SCOPE: Gla-rich protein (GRP) is a vitamin K dependent protein, characterized by
      a high density of gamma-carboxylated Glu residues, shown to accumulate in mouse
      and sturgeon cartilage and at sites of skin and vascular calcification in humans.
      Therefore, we investigated the involvement of GRP in pathological calcification
      in osteoarthritis (OA). METHODS AND RESULTS: Comparative analysis of GRP
      patterning at transcriptional and translational levels was performed between
      controls and OA patients. Using a RT-PCR strategy we unveiled two novel splice
      variants in human-GRP-F5 and F6-potentially characterized by the loss of full
      gamma-carboxylation and secretion functional motifs. GRP-F1 is shown to be the
      predominant splice variant expressed in mouse and human adult tissues,
      particularly in OA cartilage, while an overexpressing human cell model points it
      as the major gamma-carboxylated isoform. Using validated conformational
      antibodies detecting carboxylated or undercarboxylated GRP (c/uc GRP), we have
      demonstrated cGRP accumulation in controls, whereas ucGRP was the predominant
      form in OA-affected tissues, colocalizing at sites of ectopic calcification.
      CONCLUSION: Overall, our results indicate the predominance of GRP-F1, and a clear
      association of ucGRP with OA cartilage and synovial membrane. Levels of vitamin K
      should be further assessed in these patients to determine its potential
      therapeutic use as a supplement in OA treatment.

PMID- 24867293
TI  - Copy number variation of the beta defensin gene cluster on chromosome 8p
      influences the bacterial microbiota within the nasopharynx of otitis-prone
      children.
AB  - As there is increasing evidence that aberrant defensin expression is related to
      susceptibility for infectious disease and inflammatory disorders, we sought to
      determine if copy number of the beta-defensin gene cluster located on chromosome
      8p23.1 (DEFB107, 106, 105, 104, 103, DEFB4 and SPAG11), that shows copy number
      variation as a block, was associated with susceptibility to otitis media (OM).
      The gene DEFB103 within this complex encodes human beta defensin-3 (hBD-3), an
      antimicrobial peptide (AP) expressed by epithelial cells that line the mammalian
      airway, important for defense of mucosal surfaces and previously shown to have
      bactericidal activity in vitro against multiple human pathogens, including the
      three that predominate in OM. To this end, we conducted a retrospective case
      control study of 113 OM prone children and 267 controls aged five to sixty
      months. We identified the copy number of the above defined beta-defensin gene
      cluster (DEFB-CN) in each study subject by paralogue ratio assays. The mean DEFB
      CN was indistinguishable between subjects classified as OM prone based on a
      recent history of multiple episodes of OM and control subjects who had no history
      of OM (4.4 +/- 0.96 versus 4.4 +/- 1.08, respectively: Odds Ratio [OR]: 1.16 (95%
      CI: 0.61, 2.20). Despite a lack of direct association, we observed a
      statistically significant correlation between DEFB-CN and nasopharyngeal
      bacterial colonization patterns. Collectively, our findings suggested that
      susceptibility to OM might be mediated by genetic variation among individuals,
      wherein a DEFB-CN less than 4 exerts a marked influence on the microbiota of the
      nasopharynx, specifically with regard to colonization by the three predominant
      bacterial pathogens of OM.

PMID- 24867295
TI  - Real-time monitoring of total polyphenols content in tea using a developed
      optical sensors system.
AB  - A portable and low-cost optical sensors system consisting of hardware and
      software was developed and used for real-time monitoring total polyphenols
      content in tea in this work. This developed system was used for data acquisition.
      Partial least square (PLS) with several variable selection algorithms was used
      for modeling. Synergy interval partial least square (Si-PLS) was first used to
      select spectral subintervals of interest, and then competitive adaptive
      reweighted sampling (CARS) and genetic algorithm (GA) were comparatively employed
      to select the variables of interest from the subintervals of interest. The
      optimum model was achieved and stored in the developed software. Next, 20
      independent samples were used to test the performance of this system. And the
      coefficient of variation (CV) of the final results was used to state the
      stability and reliability of this system. The results also showed that GA-Si-PLS
      performed better than CARS-Si-PLS model and the CVs for most of the samples were
      <5%. This study demonstrated this developed optical sensors system as a promising
      tool that could be used for real-time monitoring tea quality. 

PMID- 24867296
TI  - Discrimination of leaves of Panax ginseng and P. quinquefolius by ultra high
      performance liquid chromatography quadrupole/time-of-flight mass spectrometry
      based metabolomics approach.
AB  - In present study, an ultra high performance liquid chromatography/quadrupole time
      of-flight mass spectrometry (UHPLC-QTOF-MS/MS) based metabolomics approach was
      established to investigate the metabolic profiles and characteristic chemical
      markers for distinguishing between leaves of Panax ginseng (LPG) and Panax
      quinquefolius (LPQ). The UHPLC-QTOF-MS/MS data were subjected to principal
      component analysis (PCA) and orthogonal partial least squared discrimination
      analysis (OPLS-DA) to rapidly find the potential characteristic components of LPG
      and LPQ, and the identities of detected peaks including the potential
      characteristic components were elucidated. Totally, 86 components were identified
      from these 2 kinds of leaf samples, in which 9 ginsenosides could be regarded as
      the characteristic chemical markers for the discrimination of LPG from LPQ. These
      results suggested that UHPLC-QTOF-MS/MS based metabolomics approach is a powerful
      tool to rapidly find characteristic markers for the quality control of LPG. 

PMID- 24867297
TI  - Numerical investigations of the mechanical properties of a braided non-vascular
      stent design using finite element method.
AB  - This paper discusses various issues relating to the mechanical properties of a
      braided non-vascular stent made of a Ni-Ti alloy. The design of the stent is a
      major factor which determines its reliability after implantation into a stenosed
      non-vascular cavity. This paper presents the effect of the main structural
      parameters on the mechanical properties of braided stents. A parametric analysis
      of a commercial stent model is developed using the commercial finite element code
      ANSYS. As a consequence of the analytical results that the pitch of wire has a
      greater effect than other structural parameters, a new design of a variable pitch
      stent is presented to improve mechanical properties of these braided stents. The
      effect of structural parameters on mechanical properties is compared for both
      stent models: constant and variable pitches. When the pitches of the left and
      right quarters of the stent are 50% larger and 100% larger than that of the
      central portion, respectively, the radial stiffness in the central portion
      increases by 10% and 38.8%, while the radial stiffness at the end portions
      decreases by 128% and 164.7%, the axial elongation by 25.6% and 56.6% and the
      bending deflection by 3.96% and 10.15%. It has been demonstrated by finite
      element analysis that the variable pitch stent can better meet the clinical
      requirements.

PMID- 24867298
TI  - Once daily controlled-release pregabalin in the treatment of patients with
      fibromyalgia: a phase III, double-blind, randomized withdrawal, placebo
      controlled study.
AB  - OBJECTIVE: Safety and efficacy of a once daily controlled-released (CR)
      formulation of pregabalin was evaluated in patients with fibromyalgia using a
      placebo-controlled, randomized withdrawal design. RESEARCH DESIGN AND METHODS:
      This multicenter study included 6 week single-blind pregabalin CR treatment
      followed by 13 week double-blind treatment with placebo or pregabalin CR. The
      starting dose of 165 mg/day was escalated during the first 3 weeks, up to 495
      mg/day based on efficacy and tolerability. Patients with >=50% reduction in
      average daily pain score at the end of the single-blind phase were randomized to
      continue pregabalin CR at the optimized dose (330-495 mg/day) or to placebo. The
      primary endpoint was time to loss of therapeutic response (LTR), defined as <30%
      pain reduction relative to single-blind baseline or discontinuation owing to lack
      of efficacy or adverse event (AE). Secondary endpoints included measures of pain
      severity, global assessment, functional status, tiredness/fatigue, and sleep.
      CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT01271933. RESULTS: A total of
      441 patients entered the single-blind phase, and 63 were randomized to pregabalin
      CR and 58 to placebo. The median time to LTR (Kaplan-Meier analysis) was
      significantly longer in the pregabalin CR group than placebo (58 vs. 22 days, p =
      0.02). By trial end, 34/63 (54.0%) pregabalin CR and 41/58 (70.7%) placebo
      patients experienced LTR. Significantly more patients reported 'benefit from
      treatment' (Benefit, Satisfaction, and Willingness to Continue Scale) in the
      pregabalin CR group; no other secondary endpoints were statistically significant.
      Most AEs were mild to moderate in severity (most frequent: dizziness,
      somnolence). The percentage of pregabalin CR patients discontinuing because of
      AEs was 12.2% and 4.8% in the single-blind and double-blind phases, respectively
      (placebo, 0%). CONCLUSIONS: Time to LTR was significantly longer with pregabalin
      CR versus placebo in fibromyalgia patients who initially showed improvement with
      pregabalin CR, indicating maintenance of response. Pregabalin CR was well
      tolerated in most patients. Generalizability may be limited by study duration and
      selective population.

PMID- 24867299
TI  - Attention-deficit-hyperactivity disorder increases risk of bone fracture: a
      population-based cohort study.
AB  - AIM: Attention-deficit-hyperactivity disorder (ADHD) is a disorder that is
      associated with accidental injuries. The aim of this study was to evaluate the
      relationship between ADHD and bone fracture in children. METHOD: The study cohort
      comprised 3640 children (2874 males, 766 females; mean age 8y 5mo, SD 3y) with
      ADHD (International Classification of Diseases, Ninth Revision) who were matched
      to children without ADHD at a ratio of 1:4 (n=14 560; 11 496 males, 3064 females;
      mean age 8y 5mo, SD 3y). A Cox proportional hazard regression analysis was
      conducted to estimate how ADHD affected the risk of bone fracture. RESULTS: The
      incidence of fracture among the ADHD cohort was 197.67 per 10,000 person-years,
      and was 1.3-fold greater than in the comparison cohort (147.54 per 10,000 person
      years). The risk in children with ADHD was higher than that in children without
      ADHD (p value for log-rank test < 0.001). After adjusting for potential
      confounding factors, the ADHD cohort was 1.32 times more likely to have bone
      fracture accidents than the comparison cohort (hazard ratio, 1.32; 95% confidence
      interval 1.17-1.49). INTERPRETATION: Children with ADHD have a higher risk of
      experiencing bone fracture accidents than do children without ADHD.

PMID- 24867300
TI  - Continuity in a VA patient-centered medical home reduces emergency department
      visits.
AB  - BACKGROUND: One major goal of the Patient-Centered Medical Home (PCMH) is to
      improve continuity of care between patients and providers and reduce the
      utilization of non-primary care services like the emergency department (ED).
      OBJECTIVE: To characterize continuity under the Veterans Health Administration's
      PCMH model--the Patient Aligned Care Team (PACT), at one large Veterans Affair's
      (VA's) primary care clinic, determine the characteristics associated with high
      levels of continuity, and assess the association between continuity and ED
      visits. DESIGN: Retrospective, observational cohort study of patients at the West
      Haven VA (WHVA) Primary Care Clinic from March 2011 to February 2012. PATIENTS:
      The 13,495 patients with established care at the Clinic, having at least one
      visit, one year before March 2011. MAIN MEASURES: Our exposure variable was
      continuity of care--a patient seeing their assigned primary care provider (PCP)
      at each clinic visit. The outcome of interest was having an ED visit. RESULTS:
      The patients encompassed 42,969 total clinic visits, and 3185 (24%) of them had
      15,458 ED visits. In a multivariable logistic regression analysis, patients with
      continuity of care--at least one visit with their assigned PCP--had lower ED
      utilization compared to individuals without continuity (adjusted odds ratio [AOR]
      0.54; 95% CI: 0.41, 0.71), controlling for frequency of primary care visits,
      comorbidities, insurance, distance from the ED, and having a trainee PCP
      assigned. Likewise, the adjusted rate of ED visits was 544/1000 person-year (PY)
      for patients with continuity vs. 784/1000 PY for patients without continuity (p =
      0.001). Compared to patients with low continuity (<33% of visits), individuals
      with medium (33-50%) and high (>50%) continuity were less likely to utilize the
      ED. CONCLUSIONS: Strong continuity of care is associated with decreased ED
      utilization in a PCMH model and improving continuity may help reduce the
      utilization of non-primary care services.

PMID- 24867301
TI  - Minimally invasive rib resection with preservation of periosteum using 1-port
      video-assisted thoracoscopic surgery.

PMID- 24867302
TI  - Influence of mitral valve repair versus replacement on the development of late
      functional tricuspid regurgitation.
AB  - OBJECTIVES: To study the determinants of functional tricuspid regurgitation (TR)
      progression after surgical correction of mitral regurgitation, including the
      influence of mitral valve (MV) repair (MVr) versus replacement (MVR) for
      degenerative mitral regurgitation. METHODS: From January 1995 to January 2006,
      747 adults with MV prolapse underwent isolated MVr (n=683) or MVR (n=64;
      mechanical in 32). The mean age was 60.8 years, and 491 were men (66.0%).
      Moderate preoperative functional TR was present in 115 (15.4%). The MVR group had
      a greater likelihood of New York Heart Association class III or IV (75.0% vs
      34.4%, P<.001), atrial fibrillation (20.3% vs 8.3%, P=.002), a lower left
      ventricular ejection fraction (61.0% vs 65.2%, P<.003), and a higher pulmonary
      artery pressure (50.1 vs 41.2 mm Hg, P=.001). The patients were monitored for a
      mean of 6.9 years (MVr) or 7.7 years (MVR; P=.075). RESULTS: During late follow
      up, no difference was found between the groups in the development of moderately
      severe or severe TR: 1 to 5 years (3.0% vs 3.3%, P=.91) and >5 years (6.1% vs
      6.5%; P=.93). The univariate predictors of severe TR after 5 years were older age
      (hazard ratio [HR], 1.1; P=.011), female gender (HR, 6.86; P=.005), higher
      pulmonary artery pressure (HR, 1.05; P=.022), and larger left atrial size (HR,
      2.11; P=.035). Two patients (0.26%) who had undergone initial MVr required
      reoperation for late functional TR. Another 2 patients had had the tricuspid
      valve addressed concurrent with reoperation for MVr failure. No tricuspid
      reoperations were required in the MVR group. CONCLUSIONS: The risk of TR
      progression was low after MVr or MVR for MV prolapse. Timely MV surgery before
      the development of left atrial dilatation or pulmonary hypertension could further
      decrease the risk of TR progression during follow-up.

PMID- 24867303
TI  - BBS4 is necessary for ciliary localization of TrkB receptor and activation by
      BDNF.
AB  - Primary cilia regulate an expanding list of signaling pathways in many different
      cell types. It is likely that identification of the full catalog of pathways
      associated with cilia will be necessary to fully understand their role in
      regulation of signaling and the implications for diseases associated with their
      dysfunction, ciliopathies. Bardet-Biedl Syndrome (BBS) is one such ciliopathy
      which is characterized by a spectrum of phenotypes. These include neural defects
      such as impaired cognitive development, centrally mediated hyperphagia and
      peripheral sensory defects. Here we investigate potential defects in a signaling
      pathway associated with neuronal function, brain derived neurotrophic factor
      (BDNF) signaling. Upon loss of BBS4 expression in cultured cells, we observed
      decreased phosphorylation and activation by BDNF of its target receptor, TrkB.
      Assessment of ciliary localization revealed that, TrkB localized to the axonemes
      or basal bodies of cilia only in the presence of BDNF. Axonemal localization,
      specifically, was abrogated with loss of BBS4. Finally, we present evidence that
      loss of the ciliary axoneme through depletion of KIF3A impedes activation of
      TrkB. Taken together, these data suggest the possibility of a previously
      uninvestigated pathway associated with perturbation of ciliary proteins. 

PMID- 24867304
TI  - Do the socioeconomic and hypertension gradients in rural populations of low- and
      middle-income countries differ by geographical region? A systematic review and
      meta-analysis.
AB  - BACKGROUND: Of the 1 billion people with hypertension globally, two-thirds reside
      in low- and middle-income countries (LMICs). The risk of hypertension in LMICs is
      thought to be positively associated with socioeconomic status (SES). However,
      recent studies have provided data inconsistent with this concept. Thus, we
      assessed the association between SES and hypertension in rural populations of
      LMICs. Further, we explored whether this association differs according to
      geographical region. METHODS: Through a search of databases we identified
      population-based studies that presented risk estimates for the association
      between SES, or any of its proxies, and hypertension. Meta-analyses were
      conducted using a random effects model. RESULTS: Overall, no association was
      detected between educational status and hypertension, whereas a positive
      association was observed with income. Interestingly, educational status was
      inversely associated with hypertension in East Asia {effect size [ES] 0.82 [95%
      confidence interval (CI) 0.78, 0.87]} but positively associated in South Asia [ES
      1.28 (95% CI 1.14, 1.43)]. Higher income, household assets or social class were
      positively associated with hypertension in South Asia whereas no association was
      detected in East Asia and Africa. Compared with other occupations, farmers or
      manual labourers were associated with a lower risk for hypertension. Further, in
      regions such as Latin America, few studies were identified that fulfilled our
      inclusion criteria. CONCLUSIONS: We provide evidence that the association between
      hypertension and SES in rural populations of LMICs in Asia varies according to
      geographical region. This has important implications for targeting intervention
      strategies aimed at high-risk populations in different geographical regions.

PMID- 24867305
TI  - Causal associations of tobacco smoking with cardiovascular risk factors: a
      Mendelian randomization analysis of the HUNT Study in Norway.
AB  - BACKGROUND: Tobacco smoking has been associated with cardiovascular risk factors
      including adverse serum lipid levels, central obesity and higher resting heart
      rate, but lower blood pressure and body mass index (BMI). We used a Mendelian
      randomization approach to study whether these associations may be causal. If
      smoking affects cardiovascular risk factors then rs1051730 T alleles, predictors
      of increased smoking quantity, should be associated with cardiovascular risk
      factors among smokers, but not among never smokers. METHODS: Among 56,625
      participants of a population-based study, we estimated associations of rs1051730
      T alleles with cardiovascular risk factors and examined whether the associations
      differed by smoking status. RESULTS: Rs1051730 T alleles were associated with
      lower BMI and waist and hip circumferences and higher resting heart rate and
      estimated glomerular filtration rate (eGFR), and the associations were strongest
      among current smokers (P interaction 5*10(-9) to 0.01). Rs1051730 T alleles were
      associated with lower systolic blood pressure and pulse pressure and higher HDL
      cholesterol concentrations, but these associations did not robustly differ by
      smoking status. There were no convincing associations of rs1051730 T alleles with
      waist-hip ratio, diastolic blood pressure and non-fasting serum concentrations of
      non-HDL cholesterol, triglycerides, glucose and C-reactive protein. CONCLUSIONS:
      This Mendelian randomization analysis provides evidence that smoking may cause
      lower BMI and waist and hip circumferences and higher resting heart rate and
      eGFR. The findings further suggest that smoking is not a major determinant of
      waist-hip ratio or adverse blood pressure, serum lipid or glucose levels.

PMID- 24867307
TI  - Presymptomatic autoantibodies in Sjogren's syndrome: what significance do they
      hold for the clinic?
AB  - In a number of autoimmune diseases, for example, rheumatoid arthritis and
      systemic lupus erythematosus, it is known that autoantibodies are present before
      the clinical onset. Recently we have shown that autoantibodies can be found many
      years before symptom onset in primary Sjogren's syndrome. This implies that
      screening for autoantibodies may be used to identify individuals at risk of
      developing systemic autoimmune disease. Possibly, autoantibody screening may also
      contribute to detection of incipient malignancy. This concept stems from a novel
      finding, on scleroderma patients, suggesting that an anti-tumor immune response
      elicited by a mutated self-antigen will cross-react with the unmodified version
      of the self-antigen, and thus come to trigger the formation of autoantibodies. 

PMID- 24867308
TI  - Organocatalytic Lewis base functionalisation of carboxylic acids, esters and
      anhydrides via C1-ammonium or azolium enolates.
AB  - This tutorial review highlights the organocatalytic Lewis base functionalisation
      of carboxylic acids, esters and anhydrides via C1-ammonium/azolium enolates. The
      generation and synthetic utility of these powerful intermediates is highlighted
      through their application in various methodologies including aldol
      lactonisations, Michael-lactonisations/lactamisations and [2,3]-rearrangements. 

PMID- 24867309
TI  - Dithiaarsanes induce oxidative stress-mediated apoptosis in HL-60 cells by
      selectively targeting thioredoxin reductase.
AB  - The selenoprotein thioredoxin reductase (TrxR) plays a pivotal role in regulating
      cellular redox homeostasis and has attracted increasing attention as a promising
      anticancer drug target. We report here that 2-(4-aminophenyl)-1,3,2-dithiarsinane
      (PAO-PDT, 4), a potent and highly selective small molecule inhibitor of TrxR,
      stoichiometrically binds to the C-terminal selenocysteine/cysteine pair in the
      enzyme in vitro and induces oxidative stress-mediated apoptosis in HL-60 cells.
      The molecular action of 4 in cells involves inhibition of TrxR, elevation of
      reactive oxygen species, depletion of cellular thiols, and activation of caspase
      3. Knockdown of TrxR sensitizes the cells to 4 treatment, whereas overexpression
      of the functional enzyme alleviates the cytotoxicity, providing physiological
      relevance for targeting TrxR by 4 in cells. The simplicity of the structure and
      the presence of an easily manipulated amine group will facilitate the further
      development of 4 as a potential cancer chemotherapeutic agent. 

PMID- 24867310
TI  - Open reduction and posterior instrumentation of type 3 high transverse sacral
      fracture-dislocation: technical note.
AB  - The authors describe an open reduction and fixation through a posterior approach
      of Roy-Camille Type 3 transverse sacral fractures. This technique involves
      posterior staged reduction of the fracture applying distraction forces to restore
      the height, followed by posterior translation to restore sagittal alignment. Tips
      and pearls of this procedure, described for the first time in the literature, are
      also discussed in this report. 

PMID- 24867311
TI  - Increased serum VEGF and b-FGF in Graves' ophthalmopathy.
AB  - BACKGROUND: Graves' ophthalmopathy (GO) is thought to be an inflammatory disorder
      of autoimmune background. The aim of this study is to investigate the involvement
      of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor
      (b-FGF) in patients with Graves' ophthalmopathy (GO). METHODS: Serum
      concentrations of VEGF and b-FGF of 48 GO patients, 30 Graves' hyperthyroid
      disease (GD) patients without ophthalmopathy, and 30 healthy controls were
      measured by Enzyme-Linked Immunosorbent Assay (ELISA). Patients with GO were
      subdivided into two groups according to clinical activity scores (CAS): a score
      of 3 or less is considered as inactive (CAS <= 3, inactive GO, n = 14), and 4 or
      more is considered active eye disease (CAS >= 4, active GO; n = 34). All of the
      patients with active GO underwent corticosteroid therapy. RESULTS: The
      concentrations of serum VEGF and b-FGF were significantly higher in patients with
      GO and in those with GD than in controls. The serum levels of VEGF and b-FGF in
      patients with active GO were higher than those in patients with inactive GO and
      those in GD patients (P < 0.05). Moreover, serum VEGF and b-FGF concentratison
      were significantly correlated with CAS in GO patients (p < 0.01). Mean VEGF and b
      FGF levels in corticosteroid-responsive patients (CAS decreases >=3 after
      treatment) decreased significantly after corticosteroid treatment (P < 0.05), and
      these changes were accompanied by a decrease of CAS (P < 0.05). CONCLUSION: The
      results suggest that serum VEGF and b-FGF levels were increased in patients with
      active GO and could reflect the degree of ocular inflammatory activity.

PMID- 24867312
TI  - Trans-conjunctival aqueous humor outflow in glaucomatous patients treated with
      prostaglandin analogues: an in vivo confocal microscopy study.
AB  - PURPOSE: To analyze, using in vivo laser scanning confocal microscopy (LSCM), the
      conjunctival features in glaucomatous patients receiving prostaglandin analogues
      (PGA). METHODS: Eighty eyes of 80 consecutive glaucomatous patients naive for
      therapy were enrolled; 30 eyes of 30 healthy subjects served as a control.
      Patients were randomized to: preservative-free (PF) and preserved latanoprost
      (groups 1 and 2, respectively), PF and preserved timolol (groups 3 and 4), and
      controls to vehicle of latanoprost or physiological buffered saline solution
      (groups 5 and 6). All subjects underwent LSCM of bulbar conjunctiva at baseline
      and 3 months after initiating therapy. The main outcomes were: mean density (MMD:
      cysts/mm(2)) and mean area (MMA: cysts/mm(2)) of epithelial microcysts. The
      relations between MMA and MMD with intraocular pressure (IOP), age, and mean
      defect (MD), were analyzed. RESULTS: At baseline, microcysts were found in all
      subjects. At month three, MMD did not change in all groups (p > 0.05). MMA
      significantly increased only in group 1 from 2,158.81 +/- 524.09 to 3,877.77 +/-
      867.31, and in group 2 from 2,019.71 +/- 541.03 to 5,560.39 +/- 1,176.14, with
      values significantly higher in group 2 (p < 0.001). Significant relations were
      not found between MMD and MMA with IOP, MD, and age (p > 0.05). CONCLUSIONS: PGA
      increased MMA in therapy-naive glaucomatous patients, indicating a possible
      enhancement of the trans-conjunctival aqueous humor outflow. Therefore,
      conjunctiva seems an additional target tissue to evaluate the hydrodynamic
      pathways in glaucoma and modifications induced by medical therapy.

PMID- 24867313
TI  - Assessing visual acuity across five disease types: ETDRS charts are faster with
      clinical outcome comparable to Landolt Cs.
AB  - BACKGROUND: Given the diversity of visual acuity tests being employed across the
      world, we compared two frequently applied tests: ETDRS charts and an eight
      orientation projected Landolt C test in accordance with ISO 8596 and DIN 58220
      part 3. The goals of the investigation were to determine (i) test agreement and
      (ii) test-retest reliability, to assess (iii) test durations, and (iv) the
      acceptance of the tests by the examinees as well as the subjects' coping with the
      tests as rated by the examiner. METHODS: Seventy-five adult subjects with a
      visual acuity of >=0.2 (4/20) were included in one of the following groups:
      normal, media opacity, maculopathy, optic neuropathy, (post)chiasmal lesion, or
      amblyopia. Visual acuity testing was carried out monocularly, in balanced
      randomized order and in two runs for each test on the same eye, applying forced
      choice. RESULTS: Agreement: Within each group, all tests were performed
      similarly, within +/-0.048 logMAR. Reliability: Across all subject groups, with a
      probability of 95 %, test-retest differences were <0.18 logMAR for both ETDRS and
      Landolt tests. DURATION: The Landolt test lasted, on average, 1.8 times longer
      than ETDRS charts (p < 0.001). Acceptance: Examinees preferred the ETDRS test (p
      < 0.001), the examiner on average had no preference. CONCLUSION: The Landolt C
      test and the ETDRS test yielded comparable results in visual acuity and test
      retest reliability in all disease groups. The ETDRS test was usually faster and
      more accepted by both examiners and examinees than the Landolt test.

PMID- 24867314
TI  - Active surveillance and surgery in localized prostate cancer.
AB  - Prostate cancer (PCa) is the most commonly diagnosed non-cutaneous cancer and
      also the second leading cause of cancer deaths among men. Concerns about
      overdiagnosis and overtreatment of PCa have been growing, leading to more
      conservative approaches, especially in the treatment of low-risk disease. As PCa
      is a relatively slow-growing tumor, complications of unnecessary curative
      management in low-risk PCa can be prevented by active surveillance (AS). AS helps
      to improve quality of life after deferred treatment. Several AS criteria have
      been suggested for delayed treatment. Although upgrading and/or upstaging of
      cancer is a limitation of AS, many reports have shown low rates of cancer
      specific mortality up to now. Radical prostatectomy (RP) has been considered as
      standard treatment for prostate cancer to provide good oncologic outcomes. The
      increasing use of minimally invasive laparoscopic surgery, including robot
      assisted laparoscopic prostatectomy, has contributed to better functional
      outcomes. So far, long-term randomized studies have not conclusively proven the
      superiority of either AS or RP. Well-designed long-term randomized studies will
      be required to compare the benefits of AS and immediate RP. Here, we review
      recent reports on the current status of AS and RP, including delayed RP, and
      discuss their merits in the management of localized PCa. 

PMID- 24867315
TI  - A two-step tandem reaction to prepare hydroxamic acids directly from alcohols.
AB  - The first synthesis of hydroxamic acids from alcohols has been developed. Both
      benzylic and aliphatic alcohols can be tolerated and applied in this reaction.
      The methodology is economical, environmentally benign and high yielding. 

PMID- 24867316
TI  - Sucrose/Glucose molecular alloys by cryomilling.
AB  - We report here for the first time a series of amorphous sucrose/glucose molecular
      alloys prepared by cryomilling. Differential scanning calorimetry, X-ray powder
      diffraction and solution proton nuclear magnetic resonance showed that
      cryomilling drives a direct transformation from a two-phase mixture of
      crystalline sucrose and glucose, to a single-phase amorphous sucrose/glucose
      molecular alloy. The molecular alloys displayed a single Tg which varied linearly
      with composition. The effect of atmospheric moisture and the possibility of
      localised melting of the material because of milling-related friction were also
      discussed.

PMID- 24867317
TI  - Cytogenetic analysis of 6,142 amniocentesis cases: A 6-year single centre
      experience.
AB  - The aim of our study was to evaluate the incidences and chromosomal abnormality
      detection rates of various indications for genetic amniocentesis. We
      retrospectively analysed 6,142 amniocentesis cases performed in a single centre
      between January 2007 and April 2013. We assessed the indications for prenatal
      diagnosis, fetal karyotypes, maternal ages, fetal ultrasound findings and
      maternal serum screening results. The most common indication for genetic
      amniocentesis was an abnormal maternal serum-screening test (36.6%), followed by
      advanced maternal age (28%), advanced maternal age and an abnormal maternal serum
      screening test (14.9%) and abnormal ultrasound findings (11.2%). The highest
      positive predictive values obtained from the indications included abnormal
      ultrasound findings and abnormal maternal serum screening test (12.9%) and
      advanced maternal age (12.2%). Although advanced maternal age and abnormal
      maternal serum screening tests were the most common indicators, their association
      with abnormal ultrasound findings should be identified to increase the efficacy
      of genetic amniocentesis.

PMID- 24867318
TI  - Inflammation-induced miR-802 promotes cell proliferation in cholesteatoma.
AB  - Cholesteatoma is a destructive and abnormal skin growth consisting of
      keratinizing squamous epithelium in the middle ear. Its molecular mechanisms
      remain poorly understood. Here, we found that the NF-kappaB inflammatory
      signaling pathway was highly activated in cholesteatoma. NF-kappaB activation
      increased the expression of microRNA-802 (miR-802) and chromatin
      immunoprecipitation assays showed that P65 could uniquely bind to miR-802
      promoter. miR-802 overexpression promoted keratinocyte cell proliferation and
      cell cycle progression, while inhibition of miR-802 decreased these effects. From
      computational analysis and luciferase report assays, miR-802 directly repressed
      PTEN expression by targeting its 3'-UTR. Our results demonstrate that the NF
      kappab/miR-802/PTEN signaling pathway plays an important role in the development
      of cholesteatoma. 

PMID- 24867319
TI  - Overexpression of a lethal methylase, M.TneDI, in E. coli BL21(DE3).
AB  - A pET-based vector pDH21 expressing the methylase, M.TneDI (recognizing CGCG)
      from Thermotoga was constructed, and transformed into E. coli BL21(DE3). Despite
      E. coli BL21(DE3) being McrBC positive, 30 transformants were isolated, which
      were suspected to be McrBC(-) mutants. The overexpression of M.TneDI was verified
      by SDS-PAGE analysis. Compared to the previously constructed pJC340 vector, a
      pACYC184 derivative expressing M.TneDI from a tet promotor, the newly constructed
      pDH21 vector improved the expression of the methylase about fourfold, allowing
      complete protection of DNA substrates. This study not only demonstrates a
      practical approach to overexpressing potential lethal proteins in E. coli but
      also delivers a production strain of M.TneDI that may be useful in various in
      vitro methylation applications. 

PMID- 24867321
TI  - Times have changed...but have we?

PMID- 24867322
TI  - Illness at high altitudes.

PMID- 24867320
TI  - A novel antifungal is active against Candida albicans biofilms and inhibits
      mutagenic acetaldehyde production in vitro.
AB  - The ability of C. albicans to form biofilms is a major virulence factor and a
      challenge for management. This is evident in biofilm-associated chronic oral
      oesophageal candidosis, which has been shown to be potentially carcinogenic in
      vivo. We have previously shown that most Candida spp. can produce significant
      levels of mutagenic acetaldehyde (ACH). ACH is also an important mediator of
      candidal biofilm formation. We have also reported that D,L-2-hydroxyisocaproic
      acid (HICA) significantly inhibits planktonic growth of C. albicans. The aim of
      the present study was to investigate the effect of HICA on C. albicans biofilm
      formation and ACH production in vitro. Inhibition of biofilm formation by HICA,
      analogous control compounds or caspofungin was measured using XTT to measure
      biofilm metabolic activity and PicoGreen as a marker of biomass. Biofilms were
      visualised by scanning electron microscopy (SEM). ACH levels were measured by gas
      chromatography. Transcriptional changes in the genes involved in ACH metabolism
      were measured using RT-qPCR. The mean metabolic activity and biomass of all pre
      grown (4, 24, 48 h) biofilms were significantly reduced after exposure to HICA
      (p<0.05) with the largest reductions seen at acidic pH. Caspofungin was mainly
      active against biofilms pre-grown for 4 h at neutral pH. Mutagenic levels (>40
      uM) of ACH were detected in 24 and 48 h biofilms at both pHs. Interestingly, no
      ACH production was detected from D-glucose in the presence of HICA at acidic pH
      (p<0.05). Expression of genes responsible for ACH catabolism was up-regulated by
      HICA but down-regulated by caspofungin. SEM showed aberrant hyphae and collapsed
      hyphal structures during incubation with HICA at acidic pH. We conclude that HICA
      has potential as an antifungal agent with ability to inhibit C. albicans cell
      growth and biofilm formation. HICA also significantly reduces the mutagenic
      potential of C. albicans biofilms, which may be important when treating bacterial
      fungal biofilm infections. 

PMID- 24867323
TI  - Toxic effects of mildly elevated homocysteine concentrations in neuronal-like
      cells.
AB  - Epidemiological and experimental evidence indicated that hyperhomocysteinemia is
      associated with neurodegeneration. However, homocysteine neurotoxic effects have
      been so far investigated mostly by employing homocysteine concentrations (>=100
      uM) much higher than homocysteine mean plasma levels (20 uM) observed in patients
      with neurodegenerative disorders. While evaluating the effects of a prolonged
      exposure to ~20 uM homocysteine in neuronal-like differentiated SH-SY5Y cells, we
      observed a 35% loss of cell viability and a four-fold increase in reactive oxygen
      species levels in cells incubated with homocysteine for five days compared with
      controls. Moreover, homocysteine increased by 30% and around two-fold,
      respectively, the Comet-positive cell number and DNA damage indexes (tail length,
      T-DNA, olive tail moment) compared with controls. Cell response to homocysteine
      induced DNA damage involved the up-regulation of Bax and, at a greater extent,
      Bcl-2, but not caspase-3, in association with a p53-independent increase of p21
      levels; concomitantly, also p16 levels were increased. When looking at time
      dependent changes in cyclin expression, we found that a significant up-regulation
      of cyclins D1, A1, E1, but not B1, concomitant with p21 down-regulation, occurred
      in cells incubated with homocysteine for three days. However, in line with the
      observed increase of p21 and p16 levels, a five days incubation with homocysteine
      induced cyclin down-regulation accompanied by a strong reduction of
      phosphorylated pRB amounts. These results suggest that, when prolonged, the
      exposure of neuronal-like cells to mildly elevated homocysteine concentrations
      triggers oxidative and genotoxic stress involving an early induction of cyclins,
      that is late repressed by G1-S check-point regulators.

PMID- 24867324
TI  - The full-length cell-cell fusogen EFF-1 is monomeric and upright on the membrane.
AB  - Fusogens are membrane proteins that remodel lipid bilayers to facilitate membrane
      merging. Although several fusogen ectodomain structures have been solved,
      structural information on full-length, natively membrane-anchored fusogens is
      scarce. Here we present the electron cryo microscopy three-dimensional
      reconstruction of the Caenorhabditis elegans epithelial fusion failure 1 (EFF-1)
      protein natively anchored in cell-derived membrane vesicles. This reveals a
      membrane protruding, asymmetric, elongated monomer. Flexible fitting of a
      protomer of the EFF-1 crystal structure, which is homologous to viral class-II
      fusion proteins, shows that EFF-1 has a hairpin monomeric conformation before
      fusion. These structural insights, when combined with our observations of
      membrane-merging intermediates between vesicles, enable us to propose a model for
      EFF-1 mediated fusion. This process, involving identical proteins on both
      membranes to be fused, follows a mechanism that shares features of SNARE-mediated
      fusion while using the structural building blocks of the unilaterally acting
      class-II viral fusion proteins. 

PMID- 24867327
TI  - Synthesis of fluorinated heteroaromatics through formal substitution of a nitro
      group by fluorine under transition-metal-free conditions.
AB  - An efficient and transition-metal-free approach was developed to access a series
      of fluorinated heteroaromatics in moderate to excellent yields. This one-pot
      procedure features a triple-relay transformation of rapid dearomatization,
      fluorination, and rearomatization processes, which represents a conceptually
      novel strategy of combining partial hydrogenation and electrophilic fluorination.

PMID- 24867326
TI  - Deep brain stimulation for treatment-resistant depression: systematic review of
      clinical outcomes.
AB  - Major depressive disorder (MDD) is a widespread, severe, debilitating disorder
      that markedly diminishes quality of life. Medication is commonly effective, but
      20-30 % of patients are refractory to medical therapy. The surgical treatment of
      psychiatric disorders has a negative stigma associated with it owing to
      historical abuses. Various ablative surgeries for MDD have been attempted with
      marginal success, but these studies lacked standardized outcome measures. The
      recent development of neuromodulation therapy, especially deep brain stimulation
      (DBS), has enabled controlled studies with sham stimulation and presents a
      potential therapeutic option that is both reversible and adjustable. We performed
      a systematic review of the literature pertaining to DBS for treatment-resistant
      depression to evaluate the safety and efficacy of this procedure. We included
      only studies using validated outcome measures. Our review identified 22 clinical
      research papers with 5 unique DBS approaches using different targets, including
      nucleus accumbens, ventral striatum/ventral capsule, subgenual cingulate cortex,
      lateral habenula, inferior thalamic nucleus, and medial forebrain bundle. Among
      the 22 published studies, only 3 were controlled trials, and 2, as yet
      unpublished, multicenter, randomized, controlled trials evaluating the efficacy
      of subgenual cingulate cortex and ventral striatum/ventral capsule DBS were
      recently discontinued owing to inefficacy based on futility analyses. Overall,
      the published response rate to DBS therapy, defined as the percentage of patients
      with > 50 % improvement on the Hamilton Depression Rating Scale, is reported to
      be 40-70 %, and outcomes were comparable across studies. We conclude that DBS for
      MDD shows promise, but remains experimental and further accumulation of data is
      warranted.

PMID- 24867329
TI  - Antidepressant-like effects of omega-3 fatty acids in postpartum model of
      depression in rats.
AB  - Postpartum depression (PPD) is a psychiatric disorder that occurs in 10-15% of
      childbearing women. It is hypothesized that omega-3 fatty acids, which are
      components of fish oil, may attenuate depression symptoms. In order to examine
      this hypothesis, the animal model of postpartum depression was established in the
      present study. Ovariectomized female rats underwent hormone-simulated pregnancy
      (HSP) regimen and received progesterone and estradiol benzoate or vehicle for 23
      days, mimicking the actual rat's pregnancy. The days after hormone termination
      were considered as the postpartum period. Forced feeding of menhaden fish oil, as
      a source of omega-3, with three doses of 1, 3, and 9g/kg/d, fluoxetine 15mg/kg/d,
      and distilled water 2ml/d per rat started in five postpartum-induced and one
      vehicle group on postpartum day 1 and continued for 15 consecutive days. On
      postpartum day 15, all groups were tested in the forced swimming test (FST) and
      open field test (OFT), followed by a biochemical assay. Results showed that the
      postpartum-induced rats not treated with menhaden fish oil, exhibited an increase
      in immobility time seen in FST, hippocampal concentration of corticosterone and
      plasmatic level of corticosterone, and pro-inflammatory cytokines. These
      depression-related effects were attenuated by supplementation of menhaden fish
      oil with doses of 3 and 9g/kg. Moreover, results of rats supplemented with
      menhaden fish oil were comparable to rats treated with the clinically effective
      antidepressant, fluoxetine. Taken together, these results suggest that menhaden
      fish oil, rich in omega-3, exerts beneficial effect on postpartum depression and
      decreases the biomarkers related to depression such as corticosterone and pro
      inflammatory cytokines.

PMID- 24867328
TI  - Integrative transcriptome meta-analysis reveals widespread sex-biased gene
      expression at the human fetal-maternal interface.
AB  - As males and females share highly similar genomes, the regulation of many
      sexually dimorphic traits is constrained to occur through sex-biased gene
      regulation. There is strong evidence that human males and females differ in terms
      of growth and development in utero and that these divergent growth strategies
      appear to place males at increased risk when in sub-optimal conditions. Since the
      placenta is the interface of maternal-fetal exchange throughout pregnancy, these
      developmental differences are most likely orchestrated by differential placental
      function. To date, progress in this field has been hampered by a lack of genome
      wide information on sex differences in placental gene expression. Therefore, our
      motivation in this study was to characterize sex-biased gene expression in the
      human placenta. We obtained gene expression data for >300 non-pathological
      placenta samples from 11 microarray datasets and applied mapping-based array
      probe re-annotation and inverse-variance meta-analysis methods which showed that
      >140 genes (false discovery rate (FDR) <0.05) are differentially expressed
      between male and female placentae. A majority of these genes (>60%) are
      autosomal, many of which are involved in high-level regulatory processes such as
      gene transcription, cell growth and proliferation and hormonal function. Of
      particular interest, we detected higher female expression from all seven genes in
      the LHB-CGB cluster, which includes genes involved in placental development, the
      maintenance of pregnancy and maternal immune tolerance of the conceptus. These
      results demonstrate that sex-biased gene expression in the normal human placenta
      occurs across the genome and includes genes that are central to growth,
      development and the maintenance of pregnancy. 

PMID- 24867325
TI  - Neuropathic pain and deep brain stimulation.
AB  - Deep brain stimulation (DBS) is a neurosurgical intervention the efficacy,
      safety, and utility of which are established in the treatment of Parkinson's
      disease. For the treatment of chronic, neuropathic pain refractory to medical
      therapies, many prospective case series have been reported, but few have
      published findings from patients treated with current standards of neuroimaging
      and stimulator technology over the last decade . We summarize the history,
      science, selection, assessment, surgery, programming, and personal clinical
      experience of DBS of the ventral posterior thalamus,
      periventricular/periaqueductal gray matter, and latterly rostral anterior
      cingulate cortex (Cg24) in 113 patients treated at 2 centers (John Radcliffe,
      Oxford, UK, and Hospital de Sao Joao, Porto, Portugal) over 13 years. Several
      experienced centers continue DBS for chronic pain, with success in selected
      patients, in particular those with pain after amputation, brachial plexus injury,
      stroke, and cephalalgias including anesthesia dolorosa. Other successes include
      pain after multiple sclerosis and spine injury. Somatotopic coverage during awake
      surgery is important in our technique, with cingulate DBS under general
      anesthesia considered for whole or hemibody pain, or after unsuccessful DBS of
      other targets. Findings discussed from neuroimaging modalities, invasive
      neurophysiological insights from local field potential recording, and autonomic
      assessments may translate into improved patient selection and enhanced efficacy,
      encouraging larger clinical trials.

PMID- 24867331
TI  - SSRI or CRF antagonism partially ameliorate depressive-like behavior after
      adolescent social defeat.
AB  - Depression and anxiety during adolescence are complex disorders due to persistent
      effects on physiology and behavior. Selective-serotonin reuptake inhibitors
      (SSRI) are currently the most widely used pharmacological intervention for
      depression. Corticotropin-releasing factor one (CRF1) receptor antagonists
      represent a novel class of compounds that may have efficacy for depressive and
      anxiety disorders. This study used an animal model of chronic adolescent stress
      to determine the efficacy of the SSRI fluoxetine, and a novel CRF1 receptor
      antagonist, GSK876008, on prevention of the behavioral effects of chronic
      adolescent stress. Male rats were exposed to chronic social defeat stress,
      fluoxetine, and/or GSK876008 from postnatal day 28-50. Chronic stress-induced
      depressive-like behaviors were partially attenuated by either concurrent
      fluoxetine or GSK876008. Fluoxetine blunted body mass gain in the adolescents
      exposed to chronic stress. The collective data demonstrate similar efficacy
      between a SSRI and a CRF1 receptor antagonist in the attenuation of stress
      induced anhedonia but fewer side effects were observed in those rats treated with
      the CRF1 receptor antagonist. These data suggest that CRF1 receptor antagonists
      may be a viable alternative for treatment of depressive behaviors in adolescents.

PMID- 24867332
TI  - Forced swim and chronic variable stress reduced hippocampal cell survival in OVX
      female rats.
AB  - Stress and glucocorticoids induce effects on neuronal and behavioral function.
      These effects may depend on the study design and importantly on the nature and
      duration of the stressor. We have previously observed that a single exposure to
      the forced swim test (FST) caused long-lasting effects on the HPA axis response
      and hippocampal cell survival. In despite that the FST and the chronic variable
      stress (CVS) paradigm are not strictly comparable; the aim of this study was to
      compare their effects on the respective depressive-like behavior, the serum
      corticosterone levels and cell proliferation and survival in ovariectomized
      female rats. Cell proliferation was determined by Ki67-labeling, while cell
      survival was analyzed with BrdU, a thymidine analog. The results showed that FST
      increased immobility and corticosterone levels at the same time that it decreased
      cell survival without modifying cell proliferation. In contrast, after 5 weeks of
      CVS there was a sharp reduction in sucrose intake, cell proliferation and
      survival, but a lack of effect on corticosterone levels. The FST produced a
      reduction on newborn cell survival analogous to that exerted by CVS. These data
      suggest that the FST could be considered as an attractive model to study some
      kind of stress-related disorders. 

PMID- 24867330
TI  - Cannabinoids negatively modulate striatal glutamate and dopamine release and
      behavioural output of acute D-amphetamine.
AB  - The cannabinoid system plays a regulatory role in neurotransmission and is
      involved in the central actions of psychostimulants. This complex interaction
      between the cannabinoid system and psychostimulants represents a potential
      pharmacological target for psychosis and addiction. However, most studies have
      focused on cocaine, therefore, it is unclear whether these findings can be
      extended to other psychostimulants such as the amphetamines. The present study
      investigated the effects of WIN55,212-2, a synthetic cannabinoid and SR141716A, a
      CB1 receptor antagonist, on D-amphetamine-induced locomotor activity and
      extracellular dopamine and glutamate release in the striatum. Rats were either
      observed for locomotor activity or glutamate and dopamine neurotransmitter
      release in the striatum using in vivo microdialysis following intraperitoneal co
      administration of D-amphetamine with WIN55,212-2 or SR141716A. Our results
      demonstrated that d-amphetamine per se induced hyperlocomotion and enhanced
      dopamine and glutamate release, as expected. WIN55,212-2 dampened these effects
      when co-administered with d-amphetamine, while alone it displayed its
      characteristic biphasic motor profile coupled with increases in dopamine and
      decreases in glutamate release. SR141716A at high doses reduced D-amphetamine
      induced hyperlocomotion and completely reversed enhanced dopamine and glutamate
      release but alone had no effect. These findings validate the capacity of the
      cannabinoid system to modulate amphetamine-induced behaviour and its
      neurochemical output, in a state-dependent manner, providing insight into aspects
      of the neurobiological substrate that underlies amphetamines' psychotogenic and
      addictive properties.

PMID- 24867333
TI  - Histone modifications of the Crhr1 gene in a rat model of depression following
      chronic stress.
AB  - Multiple lines of evidence suggest a link between depression and changes in
      hypothalamic-pituitary-adrenal (HPA)-axis hormone dynamics, including altered
      regulation of the corticotrophin-releasing hormone (CRH) and its main receptor,
      corticotrophin-releasing hormone receptor 1 (CRHR1). However, the precise
      molecular mechanisms underlying depression remain poorly understood. In this
      study, we employed a model of depression in rats by subjecting animals to 21 days
      of chronic unpredictable mild stress (CUMS). Real-time PCR and western blotting
      were used to study the mRNA and protein expression levels of CRHR1 in the
      hypothalamus. In addition, chromatin immunoprecipitation assays were used to
      detect histone methylation at the Crhr1 gene promoter; the levels of histone H3
      trimethylation at lysines 4 (H3K4) and 9 (H3K9) reflect active transcription and
      transcriptional repression, respectively. Rats exposed to CUMS exhibited
      significant reduction in locomotion and sucrose preference. These behavioral
      alterations were associated with elevated expression levels of CRHR1 mRNA and
      protein in the hypothalamus of rats in the CUMS group. We also found that the
      levels of H3K9 trimethylation at the Crhr1 gene promoter in the CUMS group were
      significantly lower than those in the control group, whereas H3K4 trimethylation
      levels were the same for both groups. Taken together, our findings suggest that
      the increase in CRHR1 expression in the hypothalamus of stressed rats correlates
      with a decrease in the repressive chromatin state caused by reduced H3K9
      trimethylation levels. These data are the first in vivo evidence of a role for
      chromatin modifications in the regulation of Crhr1 gene expression in the
      hypothalamus, and may provide novel insight into therapeutic approaches to treat
      depression. 

PMID- 24867334
TI  - Manipulation of GABA in the ventral pallidum, but not the nucleus accumbens,
      induces intense, preferential, fat consumption in rats.
AB  - Injections of the GABAA antagonist bicuculline into the medial ventral pallidum
      (VPm) induce marked increases in food intake, but nothing is known about the way
      in which these injections alter the distribution of intake in a macronutrient
      selection situation. We investigated this topic by adapting rats to a diet
      containing independent sources of protein, carbohydrate and fat, and then
      examining the effects of intra-VPm bicuculline on diet selection. Under these
      conditions, bicuculline produced a massive, preferential increase in fat intake
      with subjects consuming a mean of 97% of their calories from fat. Furthermore,
      all treated subjects ate fat before any other macronutrient, suggesting that the
      animals' behavior was directed selectively toward this dietary component even
      before consumption had begun. Similar effects were not observed following food
      deprivation, which exerted its largest effect on carbohydrate intake. To compare
      the intra-VPm bicuculline response to that seen after activation of GABA
      receptors in the nucleus accumbens shell (AcbSh), a major source of projections
      to the VPm, we conducted similar experiments with intra-AcbSh injections of
      muscimol and baclofen. These injections also enhanced food intake, but did not
      reproduce the selective preference for fat seen after intra-VPm bicuculline.
      These experiments provide the first demonstration of preferential enhancement of
      fat intake following manipulations of a nonpeptide neurotransmitter. Since mean
      intakes of fat under baseline conditions and after deprivation tended to be lower
      than those of carbohydrates, it seems unlikely that the effects of intra-VPm
      bicuculline are related to the intrinsic "rewarding" properties of fat, but might
      rather reflect the induction of a state of "fat craving." 

PMID- 24867335
TI  - Increased number of orexin/hypocretin neurons with high and prolonged external
      stress-induced depression.
AB  - It has been found that dysregulation in the orexin/hypocretin (Ox/HCRT)
      neuropeptide system in the lateral hypothalamus (LHA) is known to affect sleep
      disorder, depression and motor activities. However, to date there is no common
      agreement regarding the resulting specific changes induced in the Ox system. In
      this study, we inject corticosterone to produce stress-induced depressed mice and
      investigate the Ox neuronal and corresponding behavioural changes. Different
      doses (10, 20, 50mg/kgbw) of corticosterone were injected in adult mice, and then
      were tested in the open field test, forced swim test, tail suspension test,
      elevated plus maze test and motor activity measurements to validate the depressed
      animal model. Significant dose-dependent behavioural changes were observed in
      correlation with the doses of corticosterone. The effect is most significant and
      robust in the high 50mg/kgbw dose group five weeks after injection.
      Interestingly, we found on average a reduction in motor activity during the 12
      hour dark phase (awake) of the depressed mice and no significant change during
      the light phase (asleep). Finally, using confocal microscopy, immunofluorescence
      (IF) analysis shows a significant increase (~20%) in the number of Ox neurons in
      the LHA of the depressed mice as compared to the age-matched controls. This study
      suggests that an increase in Ox neuronal signaling may be functionally linked to
      high and prolonged external stress-induced depression. 

PMID- 24867337
TI  - Sex definitions and gender practices. An update from Australia.
AB  - In recent years the Australian parliament has been considering the rights to
      protection from discrimination of intersex and gender identity disorder (GID)
      people. In 2013 such protections were made law in the amendment to the Sex
      Discrimination Act 1984, which in turn has influenced Senate inquiries into the
      medical treatment of intersex people. This year's Australian report describes the
      purview and the potential ramifications of the inquiry of the Senate Standing
      Committees on Community Affairs, published in October 2013, into the involuntary
      or coerced sterilization of intersex people in Australia.

PMID- 24867338
TI  - Lateral and vertical stiffness of the epitaxial h-BN monolayer on Rh(111).
AB  - The response to strain in covalently bound single layers has a large impact on
      the growth and properties. We investigate the quasi-two-dimensional hexagonal
      boron nitride on Rh(111), which is interesting due to its high intrinsic
      corrugation. We use combined atomic force and scanning tunneling microscopy to
      measure the response of this monolayer to probing forces. Three-dimensional force
      maps and the atomic resolution of the layer enable us to determine lateral and
      vertical stiffness of this prototypical system with unprecedented spatial
      resolution. Extremely low stiffnesses ~1 N/m are derived. Our experiments give
      insights into the mechanical properties of corrugated incommensurate layers that
      buckle into the third dimension to relieve strain. 

PMID- 24867339
TI  - When once is not enough: the case for repeated biopsychosocial assessments in
      psychosis.

PMID- 24867336
TI  - Melatonin and its metabolites ameliorate ultraviolet B-induced damage in human
      epidermal keratinocytes.
AB  - We investigated the protective effects of melatonin and its metabolites: 6
      hydroxymelatonin (6-OHM), N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK), N
      acetylserotonin (NAS), and 5-methoxytryptamine (5-MT) in human keratinocytes
      against a range of doses (25, 50, and 75 mJ/cm2) of ultraviolet B (UVB)
      radiation. There was significant reduction in the generation of reactive oxygen
      species (50-60%) when UVB-exposed keratinocytes were treated with melatonin or
      its derivatives. Similarly, melatonin and its metabolites reduced the nitrite and
      hydrogen peroxide levels that were induced by UVB as early as 30 min after the
      exposure. Moreover, melatonin and its metabolites enhanced levels of reduced
      glutathione in keratinocytes within 1 hr after UVB exposure in comparison with
      control cells. Using proliferation assay, we observed a dose-dependent increase
      in viability of UVB-irradiated keratinocytes that were treated with melatonin or
      its derivatives after 48 hr. Using the dot-blot technique and immunofluorescent
      staining we also observed that melatonin and its metabolites enhanced the DNA
      repair capacity of UVB-induced pyrimidine photoproducts (6-4)or cyclobutane
      pyrimidine dimers generation in human keratinocytes. Additional evidence for
      induction of DNA repair in cells exposed to UVB and treated with the indole
      compounds was shown using the Comet assay. Finally, melatonin and its metabolites
      further enhanced expression of p53 phosphorylated at Ser-15 but not at Ser-46 or
      its nonphosphorylated form. In conclusion, melatonin, its precursor NAS, and its
      metabolites 6-OHM, AFMK, 5-MT, which are endogenously produced in keratinocytes,
      protect these cells against UVB-induced oxidative stress and DNA damage.

PMID- 24867341
TI  - ESAT and M-CHAT as screening instruments for autism spectrum disorders at 18
      months in the general population: issues of overlap and association with clinical
      referrals.
AB  - The Modified Checklist for Autism in Toddlers (M-CHAT) and the Early Screening of
      Autistic Traits (ESAT) were designed to screen for autism spectrum disorders in
      very young children. The aim of this study was to explore proportions of children
      that screened positive on the ESAT or the M-CHAT and to investigate if screening
      positive on the ESAT and M-CHAT is associated with clinical referral by 18 months
      and other aspects of children's development, health, and behavior. In this study,
      the mothers of 12,948 18-month-old children returned a questionnaire consisting
      of items from the ESAT and M-CHAT, plus questions about clinical and
      developmental characteristics. The M-CHAT identified more screen-positive
      children than the ESAT, but the ESAT was associated with more clinical referrals
      and tended to identify more children with medical, language, and behavioral
      problems. A post hoc analysis of combining the two instruments found this to be
      more effective than the individual instruments alone in identifying children
      referred to clinical services at 18 months. Further analysis at the level of
      single items is warranted to improve these screening instruments. 

PMID- 24867343
TI  - A bacterial strain with a unique quadruplet codon specifying non-native amino
      acids.
AB  - The addition of noncanonical amino acids to the genetic code requires unique
      codons not assigned to the 20 canonical amino acids. Among the 64 triplet codons,
      only the three nonsense "stop" codons have been used to encode non-native amino
      acids. Use of quadruplet "frame-shift" suppressor codons provides an abundant
      alternative but suffers from low suppression efficiency as a result of competing
      recognition of their first three bases by endogenous host tRNAs or release
      factors. Deletion of release factor 1 in a genomically recoded strain of E. coli
      (E. coli C321), in which all endogenous amber stop codons (UAG) are replaced with
      UAA, abolished UAG mediated translation termination. Here we show that a
      Methanocaldococcus jannaschii-derived frame-shift suppressor tRNA/aminoacyl-tRNA
      synthetase pair enhanced UAGN suppression efficiency in this recoded bacterial
      strain. These results demonstrate that efficient quadruplet codons for encoding
      non-native amino acids can be generated by eliminating competing triplet codon
      recognition at the ribosome. 

PMID- 24867345
TI  - [Good prescribing practice].
AB  - Drug prescription is the very first step initiating a cascade of events in the
      medication process. It is, hence, decisive for success or failure of any
      pharmacologic treatment. A good prescription must therefore consider (1) relevant
      patient factors and co-morbidities, (2) evidence-based knowledge on medically
      sound prescribing practices, and (3) the setting in which a prescription is
      issued. The setting will determine which partners will participate, contribute,
      and safeguard the ongoing medication process and how much responsibility can be
      shared. Partners in the medication process refer to other healthcare
      professionals dispensing the drug, teaching the patient, or administering the
      medicines. It also involves the patients or their relatives with their
      information needs and often variable motivation and conviction to use a drug. By
      issuing a prescription, the physician must provide the partners with sufficient
      and appropriate information, must ensure that they understand the meaning of the
      prescription and are able to perform their assigned tasks during the medication
      process. Lastly, medication prescription is also subject to formal constraints
      and must meet legal criteria that are relevant for reimbursement by health
      insurance companies. 

PMID- 24867344
TI  - Revisiting oxaliplatin-based regimens for advanced hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is a global health problem, as it is the sixth
      most common cancer in the world and the third leading cause of cancer-related
      death. Many patients with HCC present with disease that is not suitable for any
      potentially curative therapy; such patients are candidates for palliative
      transarterial or systemic therapies. Sorafenib is the only systemic therapy to
      demonstrate modest survival benefit over supportive care in the context of
      randomised controlled trials. However, many cytotoxic chemotherapeutics have
      achieved a range of tumour responses, but so far without convincing survival
      benefits in smaller phase II studies. In this commentary, we will review the data
      regarding the recent interest for the use of oxaliplatin-based regimens for
      advanced HCC. 

PMID- 24867346
TI  - [Good prescription practice for out-patients-quality requirements of
      prescriptions in Germany].
AB  - Because the written prescription is a central communication medium between the
      prescribing physician and the dispensing pharmacist measures to improve the
      prescription quality are top priorities. While most primary care physicians in
      Germany use electronic systems, in outpatient clinics and nursing homes and on
      special occasions such as emergency services and home visits, many prescriptions
      are still handwritten. Incorrectly and illegibly issued prescriptions impair the
      physician-pharmacist-patient relationship and thus represent a risk factor in the
      context of medication safety. Well issued prescriptions expedite the dispensing
      and thus the continuity of treatment of the patients and spare human resources by
      avoiding queries and unnecessary steps in the care process. At the same time,
      legible and unequivocal prescriptions facilitate measures for quality assurance
      by the dispensing pharmacists and are essential preconditions needed for
      insurance reimbursement. Probably the most important step to high quality
      prescriptions is the consistent use of suitable electronic prescription software.
      This is only possible if physicians are willing to cooperate and understand the
      significance and benefits of an electronic prescription system. 

PMID- 24867347
TI  - [Guide to perfect prescribing in Switzerland].
AB  - An important initial step in the medication process is prescription writing. The
      more perfect it is, the more successfully can a therapy be performed.
      Imprecisions and missing information lead to unnecessary queries or to errors
      which are often randomly discovered during a later consultation. A "perfect
      prescription" serves every individual involved in the medication process. The
      prescription document contains the instructions for the patient, the pharmacist,
      the nurse, and other health professionals involved in the therapy. The
      prescription writing process is regulated by several laws and decrees which were
      enacted to assure the greatest possible drug safety. Deviations from the norm may
      be necessary in individual cases, which require an even more responsible
      prescribing and explicit indication. 

PMID- 24867348
TI  - [Medication Reconciliation-theory and practice].
AB  - The World Health Organization initiated the project "High5s - Action on Patient
      Safety". The aim of the High5s project is to achieve a measurable, significant
      and sustained reduction in the occurrence of five serious patient safety problems
      within five years, in five countries. One of these patient safety issues is
      medication reconciliation - the process of assuring medication accuracy at
      transitions of care. In Germany, eleven hospitals are currently implementing
      medication reconciliation. Medication reconciliation represents the systematic
      comparison of the current patient's medication list with the medication list in
      hospital. For this purpose, Lead Technical Agencies of each participating country
      translated and adapted the standard operating procedure. This standard operating
      procedure describes the implementation and the procedure of the medication
      reconciliation process in detail. This process is divided into three parts.
      First, the best possible medication history is recorded. Second, based on those
      records, the responsible physician subsequently prescribes the medication. In the
      third step, the best possible medication history is compared with the medication
      orders at admission. During this process, it is likely that some discrepancies
      will occur. Such discrepancies are discussed with the responsible physician and
      clarified. A comprehensive acquisition of the best possible medication history is
      thus particularly important. It will be part of medical records throughout the
      patients' hospital stay. Thus it will be used as an additional source for
      comparison and adjustment of patients' medication in order to facilitate optimal
      drug treatment during the entire hospital stay. The practical implementation of
      medication reconciliation requires extensive change of the current prescription
      sheets or prescription software. Thus, this provides a great challenge for many
      hospitals. Nevertheless, in the Netherlands it has been shown that it is possible
      to prevent 90 % of unintentional discrepancies with medication reconciliation. A
      German hospital recently showed a reduction of discrepancies by about 77 %. The
      use of medication reconciliation to improve clinical endpoints is currently
      subject of further studies. 

PMID- 24867349
TI  - [Formal criteria for good prescribing in the hospital].
AB  - The provision of drugs to hospitalised patients is a complex process with the
      involvement of different healthcare professionals. As pharmacotherapy is (1) one
      of the most common medical interventions, (2) a high-risk procedure, and (3)
      affects the majority of hospitalised patients, medication errors have sustainable
      impact on patient safety. Although medication errors can occur at different
      stages of drug use (prescribing, dispensing, administration), they are most
      likely within the prescribing process. According to the Reason's model of
      accident causation, these errors can be divided into active failures, error
      provoking conditions, and latent conditions. Commonly, the complex interaction
      between lacking knowledge and/or experience, rule-based mistakes, skill-based
      slips and memory lapses, inadequate working environment (exessive work load,
      fatigue) as well as poor communication and safety culture is causative for
      prescribing errors. Therefore, good prescribing should include the following
      items: Adherence to formal criteria (e. g. avoidance of abbreviations),
      performance of medication reconciliation, implementation of an electronic
      prescribing system (computerised physician order entry, CPOE) - preferably
      combined with a clinical decision support system (CDSS), education and training
      as well as the establishment of a positive error management culture. The
      implementation of recommendations to reduce prescribing errors is described on
      the basis of established processes in hospitals. 

PMID- 24867350
TI  - [Criteria for good prescribing practice in children].
AB  - Paediatric prescribing is complex. A whole range of aspects needs to be
      considered to achieve an efficacious and safe drug therapy for children. Legal
      requirements for prescribing are clearly insufficient for this purpose. Children
      are immature individuals under constant growth and development. Consequently,
      based on age and cognitive abilities of the child individual drugs and dosing
      regimens have to be chosen. Frequent off-label use and a lack of age-appropriate
      formulation worsen the situation. Additionally, not all dosage forms are
      similarly adequate in different age groups. Taste significantly influences
      patient adherence. Dose calculations based on body weight are prone to errors,
      putting a point on the wrong place or mixing up measuring units easily result in
      ten-fold dosing errors. Computer-based tools to enhance prescribing are promising
      but, however, not yet widely implemented in paediatrics because of missing
      evidence-based data sources and the hugely complex process. Communication between
      clinicians and pharmacists as well as with the patient remains very important. 

PMID- 24867351
TI  - [Good prescribing practice in the elderly].
AB  - Elderly patients are the most important target group of pharmacotherapy. Older
      individuals often suffer from multiple co-morbidities, which often results in
      polypharmacy. A therapy based on guidelines can be problematic and is only rarely
      examined in clinical trials of elderly patients. In addition, alterations in
      pharmacokinetics and pharmacodynamics due to increased age have to be considered.
      As a result of these changes, the elderly are particularly vulnerable to certain
      drugs. These drugs are classified as potentially inappropriate medication (PIM)
      for the elderly because they bear an increased risk of adverse drug events
      resulting in major safety concerns. Several classifications have been published
      to identify and avoid PIM. In this article, START/STOPP (Screening Tool to Alert
      doctors to Right Treatment/Screening Tool of Older Persons' potentially
      inappropriate Prescriptions), PRISCUS (Latin: time-honoured) as well as the
      Austrian PIM-list and FORTA (fit for the aged) criteria are discussed and
      explained in detail. The use of these tools is considered to be potentially
      useful in improving the quality of drug therapy for elderly people. Further, a
      regular medication review is recommended. The determination of the renal
      function, which is often limited in the elderly, resulting in a required dose
      adjustment of the medication as well as the choice of a low initial dose when
      starting a new drug in the elderly may also contribute to increased medication
      safety. 

PMID- 24867352
TI  - Becoming occupation-based: a case study.
AB  - This descriptive case study illustrates the experiences of a 55-year-old male
      with a chronic disability resulting from a stroke, living in the community and a
      clinician's trial using occupation-based interventions predominately in a
      rehabilitation setting. The participant engaged in occupation-based interventions
      three times a week for 5 weeks guided by the Canadian Occupational Performance
      Measure (COPM). Data were collected through semi-structured interviews during the
      intervention sessions and journal entries made by the therapist. Results
      suggested occupation-based interventions facilitated a transformation for both
      the client and the therapist by enhancing the participant's occupational
      performance and the ability to resume previous roles. The therapist's belief in
      the power and value of occupation-based practice was reinforced and validated,
      particularly in the rehabilitation of an individual with chronic stroke.

PMID- 24867354
TI  - Platelet-derived RANK ligand enhances CCL17 secretion from dendritic cells
      mediated by thymic stromal lymphopoietin.
AB  - Dendritic cells (DCs) play an integral role in cellular cascade that initiate and
      maintain Th2 responses in allergy. In this study, we examined the interaction
      between platelets and DCs to determine the role of platelets in the intervention
      of immune responses through modulation of DC functions. Blood-purified myeloid
      DCs, which had been stimulated with thymic stromal lymphopoietin (TSLP-DCs),
      formed aggregates with activated platelets. TSLP-DC maturation was induced after
      the interaction with TRAP6-activated platelets as indicated by an increase in the
      expression of CD86, CD40, and CD83. In addition, production of a Th2 cell
      attracting chemokine, CCL17, was clearly upregulated by coculture of TSLP-DCs
      with TRAP6-activated platelets. We further found that an expression of RANK
      ligand (RANKL) on platelets was upregulated by the TRAP6 activation, and that,
      using the neutralizing antibody against RANKL, the platelet-derived RANKL induces
      the activation of TSLP-DCs. Thus, activated platelets can intervene in adaptive
      immune responses through induction of functional modulation of TSLP-DCs.
      Platelets have the ability to enhance the DC-mediated Th2 response and may
      contribute to the allergic inflammation. In conclusion, our study provides new
      insights in platelet functions and the possible mechanism of allergic responses
      that stem from DCs. 

PMID- 24867356
TI  - Gemcitabine inhibits the micrometastasis of non-small cell lung cancer by
      targeting the EpCAM-positive circulating tumor cells via the HGF/cMET pathway.
AB  - Recurrence and metastasis are responsible for the death of non-small cell lung
      cancer (NSCLC) patients. Circulating tumor cells (CTCs) in the metastatic pathway
      have proven to be essential. This pilot study evaluated the sensitivity of
      gemcitabine in micrometastasis and CTCs from NSCLC patients. EpCAM-positive CTCs
      were detected in forty patients with NSCLC at treatment initiation and disease
      evaluation time-points. EpCAM-positive CTCs were defined as EpCAM-positive and
      CD45-negative. Total RNA was isolated from EpCAM-enriched CTCs and cytokeratin
      levels were detected by PCR. The HGF/cMET pathway was evaluated in CTCs from
      patients with different treatments and in A549 cells. The EMT-related markers
      were analyzed by IHC. We further explored the predictive value of baseline CTCs
      in patients that were receiving different treatments. The median number of CTCs
      in NSCLC patients was 65 CTCs/ml more than in the healthy 23?fold (median, 5.2
      CTCs/ml). The mean change in cell count was significantly different for patients
      with gemcitabine compared to patients with non-gemcitabine treatments (-86.28 vs.
      -15.23/ml; P<0.05). A significant decrease was noted in the expression of
      cytokeratin in the CTCs of the two groups (P<0.05). The HGF/cMET pathway was
      inactivated in CTCs and A549 cells treated with gemcitabine, and the cell
      migration and invasion abilities were inhibited by gemcitabine via the HGF/cMET
      pathway. Furthermore, the decreased cell migration and invasion abilities may
      also be involved in the inhibition of the epithelial-mesenchymal transition (EMT)
      by gemcitabine. At a median follow-up of 36 months, the CTC count was confirmed
      to be a robust prognostic marker in the NSCLC population (CTCs >151, median: 15.0
      months and CTCs <151, median: 32.0 months). Additionally, the survival rate in
      the gemcitabine group (24 months) was better than in non-gemcitabine group (21
      months), suggesting a therapeutic benefit for NSCLC patient survival with the
      common therapy plus gemcitabine. Gemcitabine treatment decreased EpCAM-positive
      CTCs in NSCLC patients and inhibited EMT by the HGF/cMET pathway.

PMID- 24867353
TI  - Intensive cognitive training in schizophrenia enhances working memory and
      associated prefrontal cortical efficiency in a manner that drives long-term
      functional gains.
AB  - We investigated whether intensive computerized cognitive training in
      schizophrenia could improve working memory performance and increase signal
      efficiency of associated middle frontal gyri (MFG) circuits in a functionally
      meaningful manner. Thirty schizophrenia participants and 13 healthy comparison
      participants underwent fMRI scanning during a letter N-back working memory task.
      Schizophrenia participants were then randomly assigned to either 80 h (16 weeks)
      of cognitive training or a computer games control condition. After this
      intervention, participants completed a second fMRI N-back scanning session. At
      baseline, during 2-back working memory trials, healthy participants showed the
      largest and most significant activation in bilateral MFG, which correlated with
      task performance. Schizophrenia participants showed impaired working memory,
      hypoactivation in left MFG, and no correlation between bilateral MFG signal and
      task performance. After training, schizophrenia participants improved their 2
      back working memory performance and showed increased activation in left MFG. They
      also demonstrated a significant association between enhanced task performance and
      right MFG signal, similar to healthy participants. Both task performance and
      brain activity in right MFG after training predicted better generalized working
      memory at 6-month follow-up. Furthermore, task performance and brain activity
      within bilateral MFG predicted better occupational functioning at 6-month follow
      up. No such findings were observed in the computer games control participants.
      Working memory impairments in schizophrenia and its underlying neural correlates
      in MFG can be improved by intensive computerized cognitive training; these
      improvements generalize beyond the trained task and are associated with enduring
      effects on cognition and functioning 6 months after the intervention.

PMID- 24867357
TI  - Extra-articular dorsal closing-wedge osteotomy to treat late-stage Freiberg
      disease using polyblend sutures: technical tips and clinical results.
AB  - PURPOSE: The purpose of this study was to evaluate the clinical outcomes
      regarding the dorsal wedge osteotomy fixed using a polyblend suture and describe
      the usefulness of this fixation method for the treatment of Freiberg disease.
      METHODS: The subjects consisted of 13 feet from 13 cases suffering from Freiberg
      disease that underwent extra-articular dorsal closing-wedge osteotomy using a
      polyblend suture. The average age was 31.7 (range 13-72) years. The average
      follow-up period was 17 (range 14-24) months. Regarding image findings, time to
      bone union and metatarsal shortening was reviewed. The investigation was carried
      out using the range of motion (ROM), visual analog scale (VAS), and Japanese
      Society of the Surgery of Foot lesser toe scale (JSSF score) in the MTP joint
      before surgery and at the latest follow-up. RESULTS: Calluses under the
      metatarsal head were not observed in any cases. The mean metatarsal shortening
      was 2.33 +/- 2.07 mm at follow-up. The bone union required an average of 8.4 +/-
      0.8 weeks. The average ROM of dorsal flexion improved from 37.2 +/- 5.3 degrees 
      before surgery to 73.6 +/- 9.9 degrees  at latest follow-up (p < 0.0001). The
      average ROM of plantar flexion improved from 16.0 +/- 10.1 degrees  before
      surgery to 19.5 +/- 8.6 degrees  at latest follow-up (p = 0.35). The average VAS
      significantly improved from 75.3 +/- 8.5 before surgery to 4.9 +/- 4.2 at latest
      follow-up (p < 0.0001). The average JSSF score significantly improved from 67.3
      +/- 9.4 points before surgery to 98.8 +/- 3.0 points at the latest follow-up (p <
      0.0001). CONCLUSION: Extra-articular dorsal closing-wedge osteotomy using a
      polyblend suture was carried out to treat Freiberg disease. The bone union was
      observed in all cases with improved clinical results. Fixation using a polyblend
      suture was considered to be useful.

PMID- 24867358
TI  - Mono versus polyaxial locking plates in distal femur fractures: a prospective
      randomized multicentre clinical trial.

PMID- 24867360
TI  - Two-dimensional MoS2 nanosheets as a capillary GC stationary phase for highly
      effective molecular screening.
AB  - Stable layered MoS2 nanosheets were employed as a stationary phase in gas
      chromatography. A wide range of different analytes were screened with excellent
      separation efficiency. 

PMID- 24867361
TI  - Role of acentric displacements on the crystal structure and second-harmonic
      generating properties of RbPbCO3F and CsPbCO3F.
AB  - Two lead fluorocarbonates, RbPbCO3F and CsPbCO3F, were synthesized and
      characterized. The materials were synthesized through solvothermal and
      conventional solid-state techniques. RbPbCO3F and CsPbCO3F were structurally
      characterized by single-crystal X-ray diffraction and exhibit three-dimensional
      (3D) crystal structures consisting of corner-shared PbO6F2 polyhedra. For
      RbPbCO3F, infrared and ultraviolet-visible spectroscopy and thermogravimetric and
      differential thermal analysis measurements were performed. RbPbCO3F is a new
      noncentrosymmetric material and crystallizes in the achiral and nonpolar space
      group P6m2 (crystal class 6m2). Powder second-harmonic generation (SHG)
      measurements on RbPbCO3F and CsPbCO3F using 1064 nm radiation revealed an SHG
      efficiency of approximately 250 and 300 * alpha-SiO2, respectively. Charge
      constants d33 of approximately 72 and 94 pm/V were obtained for RbPbCO3F and
      CsPbCO3F, respectively, through converse piezoelectric measurements. Electronic
      structure calculations indicate that the nonlinear optical response originates
      from the distorted PbO6F2 polyhedra, because of the even-odd parity mixing of the
      O 2p states with the nearly spherically symmetric 6s electrons of Pb(2+). The
      degree of inversion symmetry breaking is quantified using a mode-polarization
      vector analysis and is correlated with cation size mismatch, from which it is
      possible to deduce the acentric properties of 3D alkali-metal fluorocarbonates.

PMID- 24867363
TI  - Genetic analysis of Dobrava-Belgrade virus from western Serbia--a newly detected
      focus in the Balkan Peninsula.
AB  - Dobrava-Belgrade virus (DOBV) is a hantavirus species that causes the most severe
      form of haemorrhagic fever with renal syndrome (HFRS) in Europe. DOBV has been
      detected in three Apodemus rodents: A. flavicollis, A. agrarius and A. ponticus.
      These emerging viruses appear throughout the Balkan Peninsula including Serbia as
      its central part. In this study, we examined the seroprevalence, molecular
      epidemiology and phylogenetics of DOBV from A. flavicollis captured at six
      Serbian localities. Furthermore, we applied microsatellite typing of host animal
      genome to analyse the role of host kinship in DOBV animal transmission. The
      overall IgG seropositivity rate over 3 years (2008-2010) was 11.9% (22/185). All
      seropositive samples were subjected to RT-PCR and DNA sequencing for S and L
      genome segments (pos. 291-1079 nt and 2999-3316 nt, respectively). DOBV was
      genetically detected in three samples from mountain Tara in western Serbia, a
      newly detected DOBV focus in the Balkans. No sequence data from human cases from
      Serbia are available for the studied period. However, collected DOBV isolates in
      this work phylogenetically clustered together with isolates from Serbian human
      cases dating from 2002, with 1.9% nucleotide divergence. We determined the level
      of kinship between seropositive and seronegative animal groups and found no
      significant difference, suggesting that horizontal virus transmission in the
      studied population was the same within and among the hatches. Our findings are
      the first genetic detection of DOBV in rodents in Serbia. We confirm wide and
      continuous hantavirus presence in the examined parts of the Balkans, underlying
      the necessity of continual monitoring of hantavirus circulation in A.
      flavicollis.

PMID- 24867362
TI  - Activity of mitogen-activated protein kinases in the esophageal epithelium of
      patients with Barrett's esophagus.
AB  - Barrett's esophagus (BE), a complication of gastroesophageal reflux disease, is
      associated with an increased risk of esophageal cancer. Mitogen-activated protein
      kinases may play an important role in the pathogenesis of this process. We aimed
      to evaluate mitogen-activated protein kinases activity in esophageal mucosa of
      patients with BE and find possible relationship between reflux type and BE.
      Twenty-four patients (mean age: 59 years) with gastroesophageal reflux disease
      symptoms and endoscopically suspected esophageal metaplasia (ESEM) were
      prospectively enrolled for testing by a multichannel intraluminal impedance
      monitoring along with a Bilitec 2000. Endoscopic biopsies were taken from
      methylene blue-positive pit patterns (sites suggesting specialized intestinal
      metaplasia [SIM]), from 2 cm above the Z-line and from cardial parts of the
      stomach. The biopsies were analyzed for extracellular signal-regulated kinase
      (ERK), c-Jun N-terminal kinase (JNK), p38 activity by Western blot. Seventeen
      ESEMs had histologically proven metaplasia: eight patients had SIM and nine had
      gastric-type epithelia (GE). Biliary reflux was more evident in SIM (P = 0.019)
      but not in GE (P = 0.019); non-biliary reflux was typical for GE (P = 0.005) but
      not for SIM (P = 0.04). Strong activations of ERK and p38 were found
      predominantly in SIM, but not in normal esophageal mucosa (NE) (P = 0.01 and P <
      0.001 respectively). Strong signals for active JNK and p38 were detected in GE,
      but not in NE (P = 0.006 and P = 0.02 respectively). ERK activity was
      significantly higher than p38 activity in ESEM patients only with GE (P = 0.02).
      The strong activation of ERK, but not JNK is indicative of SIM. The presence of
      bile in gastroesophageal refluxate is predisposing to SIM, but not to GE in
      esophageal mucosa. 

PMID- 24867366
TI  - Dye-sensitized solar cells based on (donor-pi-acceptor)2 dyes with
      dithiafulvalene as the donor.
AB  - Dipolar metal-free sensitizers (D-pi-A; D=donor, pi=conjugated bridge,
      A=acceptor) consisting of a dithiafulvalene (DTF) unit as the electron donor, a
      benzene, thiophene, or fluorene moiety as the conjugated spacer, and 2
      cyanoacrylic acid as the electron acceptor have been synthesized. Dimeric
      congeners of these dyes, (D-pi-A)(2), were also synthesized through iodine
      induced dimerization of an appropriate DTF-containing segment. Dye-sensitized
      solar cells (DSSCs) with the new dyes as the sensitizers have cell efficiencies
      that range from 2.11 to 5.24 %. In addition to better light harvesting, more
      effective suppression of the dark current than the D-pi-A dyes is possible with
      the (D-pi-A)(2) dyes.

PMID- 24867370
TI  - Ultrafast dynamics and computational studies on diaminodicyanoquinodimethanes
      (DADQs).
AB  - Three diaminodicyanoquinodimethanes, 4-(R(1)R(2)C)-1-[(NC)2C]-C6H4 (R(1),R(2) =
      H2N, 1; R(1) = 3,5-Me2-4-OCH4H6N-, R(2) = H2N, 2; R(1) = 3,5-Me2-4-OCH4H6N-, R(2)
      = 4-Me-C5H9N, 3), were investigated using carbon-13 NMR, steady-state, and
      ultrafast transient absorption and ultrafast fluorescence spectroscopies to
      unravel the unusual characteristics of this class of chromophores. Computed
      (GIAO)B3LYP/6-31G* data for the zwitterions 1-3 using necessary solvation (PCM)
      models were shown to be in excellent agreement with observed structural and
      carbon-13 NMR data. The ground-state geometries of 1-3 contain a cationic methine
      group R(1)R(2)C- twisted from the C6H4 ring and an anionic methine group (NC)2C-
      in plane with the C6H4 ring in solution and solid state. The (13)C chemical
      shifts of the peak corresponding to the methine carbon at the (NC)2C- group of 1
      3 are observed at 32.5-34.7 ppm, which are some 55 ppm upfield compared with the
      (13)C chemical shift for the methine carbons in TCNQ, 1,4-[(NC)2C]2-C6H4. The
      decay of the excited state in diaminodicyanoquinodimethanes is fast and dominated
      by nonradiative processes on the picosecond time scale, which depends on the
      viscosity of the medium. The dynamics of the excited-state decay is therefore
      limited by conformational changes through an intramolecular twisting motion. This
      twisting motion is hindered by friction, which, in turn, also depends on the
      functional group size of the system. The dominant nonradiative pathways after
      excitation are due to twisted excited-state conformers according to TD-DFT
      computations. 

PMID- 24867371
TI  - Polyphenol Conjugates and Human Health: A Perspective Review.
AB  - In recent years, antioxidants have gained great importance because of their
      potential use in food, pharmaceutical, and cosmetic industries. This interest is
      rooted in the cumulative evidence connecting active oxygen and free radicals with
      numerous human degenerative disorders, such as cardiovascular diseases, cancer,
      aging, and atherosclerosis. Polyphenols are the major class of antioxidant able
      to reduce the oxidative damages of lipids, proteins, enzymes, carbohydrates, and
      DNA in living cells and tissues. Among the realm of polyphenol compounds,
      polyphenol conjugates have been proposed as innovative materials which, by
      combining the advantageous properties of both the components, can increase the
      efficiency of antioxidants and their range of application in nutritional and
      biomedical fields. This work is an overview of the different class of polyphenol
      conjugates, which will be analyzed in terms of nutritional and biological
      properties, showing how these bio-conjugates will positively affect the human
      health. 

PMID- 24867375
TI  - Which rivastigmine formula is better for heart in elderly patients with
      Alzheimer's disease: oral or patch?
AB  - OBJECTIVE: Rivastigmine is commonly used for the treatment of Alzheimer's disease
      (AD). All cholinesterase inhibitors, including rivastigmine, may cause cardiac
      side effects. The aim of this study is to compare the electrocardiographic (ECG)
      and hypotensive effects of formulations of rivastigmine. METHODS: Eighty-five
      newly diagnosed patients with AD who were treated with rivastigmine were
      retrospectively evaluated. The ECG records were reviewed at baseline and at
      administration of either 12 mg of oral rivastigmine or 10 cm(2) transdermal
      rivastigmine. RESULTS: When compared with the baseline, there were no changes in
      any of the ECG parameters in all of the patients (P > .05). Moreover, when
      compared with the mean change from baseline for each treatment group, there were
      no changes, except heart rate (P = .035). CONCLUSION: It was demonstrated that
      rivastigmine formulations were not associated with increased arrhythmogenic or
      hypotensive effects in elderly patients with AD and was not superior to each
      other.

PMID- 24867376
TI  - Pyrimidine nucleotide synthesis in Pseudomonas nitroreducens and the regulatory
      role of pyrimidines.
AB  - Control of pyrimidine biosynthesis in the commercially important, hydrocarbon
      utilizing bacterium Pseudomonas nitroreducens ATCC 33634 was investigated. When
      glucose-grown wild-type cells were supplemented with uracil or orotic acid, the
      pyrimidine biosynthetic activities were depressed. Pyrimidine limitation of
      glucose-grown cells of an orotate phosphoribosyltransferase mutant caused
      aspartate transcarbamoylase and dihydroorotase activities to increase by about 4
      fold while the other enzyme activities about doubled. In succinate-grown
      phosphoribosyltransferase mutant cells subjected to pyrimidine limitation,
      transcarbamoylase and dehydrogenase activities rose by about 5-fold while
      dihydroorotase activity more than tripled. In an OMP decarboxylase mutant,
      pyrimidine limitation of glucose-grown cells increased transcarbamoylase,
      dihydroorotase, dehydrogenase and phosphoribosyltransferase activities by 4-, 10
      , 6- and 3.8-fold, respectively. Pyrimidine limitation of the succinate-grown
      decarboxylase mutant cells increased aspartate transcarbamoylase or
      dihydroorotase by more than 4-fold and the other activities by about 2-fold.
      Pyrimidine biosynthetic enzyme synthesis appeared to be regulated by pyrimidines
      with the regulation being influenced by the carbon source present. Aspartate
      transcarbamoylase activity in Ps. nitroreducens was regulated at the level of
      enzyme activity since the enzyme was strongly inhibited by UDP, pyrophosphate,
      ATP and ADP. Overall, the regulation of pyrimidine biosynthesis in Ps.
      nitroreducens can be used to differentiate it from other taxonomically related
      species of Pseudomonas. 

PMID- 24867377
TI  - Role of skeletal muscle in mandible development.
AB  - As a continuation of the previous study on palate development (Rot and Kablar,
      2013), here we explore the relationship between the secondary cartilage
      mandibular condyles (parts of the temporomandibular joint) and the contributions
      (mechanical and secretory) from the adjacent skeletal musculature. Previous
      analysis of Myf5-/-:MyoD-/- mouse fetuses lacking skeletal muscle demonstrated
      the importance of muscle contraction and static loading in mouse skeletogenesis.
      Among abnormal skeletal features, micrognathia (mandibular hypoplasia) was
      detected: small, bent and posteriorly displaced mandible. As an example of
      Waddingtonian epigenetics, we suggest that muscle, in addition to acting via
      mechanochemical signal transduction pathways, networks and promoters, also exerts
      secretory stimuli on skeleton. Our goal is to identify candidate molecules at
      that muscle-mandible interface. By employing Systematic Subtractive Microarray
      Analysis approach, we compared gene expression between mandibles of amyogenic and
      wild type mouse fetuses and we identified up- and down-regulated genes. This step
      was followed by a bioinformatics approach and consultation of web-accessible
      mouse databases. We searched for individual tissue-specific gene expression and
      distribution, and for the functional effects of mutations in a particular gene.
      The database search tools allowed us to generate a set of candidate genes with
      involvement in mandibular development: Cacna1s, Ckm, Des, Mir300, Myog and Tnnc1.
      We also performed mouse-to-human translational experiments and found analogies.
      In the light of our findings we discuss various players in mandibular
      morphogenesis and make an argument for the need to consider mandibular
      development as a consequence of reciprocal epigenetic interactions of both
      skeletal and non-skeletal compartments.

PMID- 24867378
TI  - Sepsis affects most routine and cell population data (CPD) obtained using the
      Sysmex XN-2000 blood cell analyzer: neutrophil-related CPD NE-SFL and NE-WY
      provide useful information for detecting sepsis.
AB  - INTRODUCTION: The Sysmex XN-2000 analyzer can assess 36 routine and 57 cell
      population data (CPD) items. In this study, we evaluated these items as sepsis
      biomarkers. METHODS: We enrolled 280 normal control (NC) and 130 sepsis patients.
      The sepsis patients were classified as uncomplicated or complicated sepsis.
      Routine and CPD items were determined, and the results were compared at between
      the NC and sepsis groups, uncomplicated and complicated sepsis groups, and
      survivors and nonsurvivors. RESULTS: For the detection of sepsis, CPD items NE
      SFL [defined as the fluorescent light intensity of the neutrophil area on the WDF
      (white blood cell differential) scattergram] and NE-WY (defined as the
      fluorescent light distribution width of the neutrophil area on the WDF
      scattergram) showed comparative or higher AUC of 0.909 and 0.905, respectively,
      when compared with routine items such as hematocrit, hemoglobin, RBC, RDW,
      immature granulocytes count, lymphocytes count, and neutrophils count. For the
      discrimination of sepsis severity, only platelet-related items showed higher AUC
      (0.723 - 0.748) than lactic acid (0.695). For the prediction of 28-day mortality,
      only CV and SD of RDW showed higher AUC (0.766 and 0.732 each) than lactic acid
      (0.712). CONCLUSIONS: Sepsis patients demonstrated significant changes in routine
      and CPD items related to RBC, neutrophils, lymphocytes, and platelets when
      compared to NCs. Increase in CPD items NE-SFL and NE-WY, which may indicate
      neutrophil immaturity or activation, could be useful for the detection of sepsis
      patients, in conjunction with currently used surrogate sepsis biomarkers.
      However, these items did not efficiently contribute to the discrimination of
      sepsis severity or predict mortality.

PMID- 24867379
TI  - Altered temporal variance and neural synchronization of spontaneous brain
      activity in anesthesia.
AB  - Recent studies at the cellular and regional levels have pointed out the
      multifaceted importance of neural synchronization and temporal variance of neural
      activity. For example, neural synchronization and temporal variance has been
      shown by us to be altered in patients in the vegetative state (VS). This finding
      nonetheless leaves open the question of whether these abnormalities are specific
      to VS or rather more generally related to the absence of consciousness. The aim
      of our study was to investigate the changes of inter- and intra-regional neural
      synchronization and temporal variance of resting state activity in anesthetic
      induced unconsciousness state. Applying an intra-subject design, we compared
      resting state activity in functional magnetic resonance imaging (fMRI) between
      awake versus anesthetized states in the same subjects. Replicating previous
      studies, we observed reduced functional connectivity within the default mode
      network (DMN) and thalamocortical network in the anesthetized state. Importantly,
      intra-regional synchronization as measured by regional homogeneity (ReHo) and
      temporal variance as measured by standard deviation (SD) of the BOLD signal were
      significantly reduced in especially the cortical midline regions, while increased
      in the lateral cortical areas in the anesthetized state. We further found
      significant frequency-dependent effects of SD in the thalamus, which showed
      abnormally high SD in Slow-5 (0.01-0.027 Hz) in the anesthetized state. Our
      results show for the first time of altered temporal variance of resting state
      activity in anesthesia. Combined with our findings in the vegetative state, these
      findings suggest a close relationship between temporal variance, neural
      synchronization and consciousness.

PMID- 24867380
TI  - Toxicity of targeted therapy: Implications for response and impact of genetic
      polymorphisms.
AB  - Targeted therapies have unique toxicity profiles. Common adverse events include
      rash, diarrhea, hypertension, hypothyroidism, proteinuria, depigmentation, and
      hepatotoxicity. Some of these toxicities are caused by on-target, mechanism
      associated effects, which can be stratified as to whether or not the targets are
      relevant to response. Other toxicities are off-target and may be caused by the
      class of agent, e.g. antibody vs small molecule tyrosine kinase inhibitor, or by
      immune reactions or toxic metabolites. Both on- and off-target toxicities may be
      due to higher drug concentrations or altered end-organ sensitivity, which in turn
      can be a consequence of genetic polymorphisms controlling metabolism or tissue
      responsiveness. On-target toxicities are important to identify as some correlate
      with response and, hence, amelioration of these side effects is preferable to
      dose reduction or stopping drug. Toxicities secondary to relevant target impact
      may be recognized when distinct types of agents, such as antibodies and small
      molecule kinase inhibitors, with the same target have a similar side effect. For
      example, both bevacizumab and vascular endothelial growth factor receptor (VEGFR)
      kinase inhibitors cause hypertension; both epidermal growth factor receptor
      (EGFR) antibodies and kinase inhibitors cause rash; and these toxicities
      correlate with response. Herein we review common targeted agent-related
      toxicities, relevant genetic polymorphisms, and implications for response and
      patient management.

PMID- 24867386
TI  - Screening and monitoring zearalenone-producing Fusarium species by PCR and
      zearalenone by monoclonal antibodies in feed from China.
AB  - Screening of zearalenone (ZEN)-producing species and monitoring of ZEN in feed
      were performed by using anti-zearalenone monoclonal antibodies. ELISA recoveries
      of ZEN from corn distillers dried grains with solubles (DDGS) feed, corn feed,
      rice bran, soybean meal, wheat bran and rapeseed dregs were between 78.6% and
      88.6%. ZEN recovery from culture media was 96.3% at the spiked level of 500
      ug/kg. Eighty-three samples of DDGS feed, corn feed and other fee ingredients
      were collected from 11 provinces of China and analysed for ZEN. Average ZEN
      levels were 563.4 ug/kg for DDGS feed, 393.1 ug/kg for corn feed and 65.7 ug/kg
      for other feed ingredients. Eighteen Fusarium species such as Fusarium
      graminearum which could produce ZEN were isolated from corn feed and other feed
      ingredients. 

PMID- 24867385
TI  - Angle-resolved light scattering of individual rod-shaped bacteria based on
      Fourier transform light scattering.
AB  - Two-dimensional angle-resolved light scattering maps of individual rod-shaped
      bacteria are measured at the single-cell level. Using quantitative phase imaging
      and Fourier transform light scattering techniques, the light scattering patterns
      of individual bacteria in four rod-shaped species (Bacillus subtilis,
      Lactobacillus casei, Synechococcus elongatus, and Escherichia coli) are measured
      with unprecedented sensitivity in a broad angular range from -70 degrees  to 70
      degrees . The measured light scattering patterns are analyzed along the two
      principal axes of rod-shaped bacteria in order to systematically investigate the
      species-specific characteristics of anisotropic light scattering. In addition,
      the cellular dry mass of individual bacteria is calculated and used to
      demonstrate that the cell-to-cell variations in light scattering within bacterial
      species is related to the cellular dry mass and growth. 

PMID- 24867387
TI  - Unfavorable effect of trigonelline, an alkaloid present in coffee and fenugreek,
      on bone mechanical properties in estrogen-deficient rats.
AB  - SCOPE: Trigonelline (1-methylpyridinium-3-carboxylate), an alkaloid present in
      coffee and fenugreek seed, has been reported to exhibit phytoestrogenic activity.
      The aim of the present study was to investigate the effects of trigonelline on
      bone mechanical properties of rats with normal estrogen level and estrogen
      deficiency (developing osteoporosis). METHODS AND RESULTS: The experiments were
      performed on 3-month-old nonovariectomized and ovariectomized (estrogen
      deficient) Wistar rats, divided into control rats and rats receiving trigonelline
      (50 mg/kg p.o. daily) for 4 weeks. The ovariectomy was performed 7-8 days before
      the start of trigonelline administration. Serum bone turnover markers and bone
      mineralization, as well as mechanical properties of the tibial metaphysis,
      femoral diaphysis, and femoral neck were examined. Estrogen deficiency caused
      worsening of bone mineralization and mechanical properties of the tibial
      metaphysis, as well as increases in bone turnover markers. Administration of
      trigonelline did not affect the investigated parameters in nonovariectomized
      rats, but it worsened the mineralization and mechanical properties of cancellous
      bone in ovariectomized rats. CONCLUSION: Unfavorable effects of trigonelline on
      the skeletal system depended on the estrogen status. They were observed only in
      cancellous bone of estrogen-deficient rats.

PMID- 24867388
TI  - Multimorbidity and functional status assessment.
AB  - PURPOSE OF REVIEW: This review conceptualizes multimorbidity and functional
      status impairment in people living with HIV and their implication in clinical and
      research fields. RECENT FINDINGS: Multimorbidity is an increasing age-related
      condition whose prevalence is higher in HIV-infected patients compared with the
      general population. It portrays the contemporary clinical complexity of HIV care.
      Whether multimorbidity describes an accelerated or accentuated aging process is
      the matter of discussion, although some HIV variables depicting immune activation
      and chronic inflammation are associated with multimorbidity. Multimorbidity
      coupled with functional status impairment are determinants of a frailty phenotype
      and in the frailty research setting, multimorbidity can be explored as an
      endpoint for clinical studies. SUMMARY: The success of highly active
      antiretroviral therapy has significantly changed the clinical pattern of HIV
      infection, with the 'greying' of the HIV-infected population testament to its
      success. This has provided new challenges relating to the care of older patients,
      particularly with regard to the management of multimorbidity functional status
      impairment.

PMID- 24867390
TI  - Synaptic dynamics: linear model and adaptation algorithm.
AB  - In this research, temporal processing in brain neural circuitries is addressed by
      a dynamic model of synaptic connections in which the synapse model accounts for
      both pre- and post-synaptic processes determining its temporal dynamics and
      strength. Neurons, which are excited by the post-synaptic potentials of hundred
      of the synapses, build the computational engine capable of processing dynamic
      neural stimuli. Temporal dynamics in neural models with dynamic synapses will be
      analyzed, and learning algorithms for synaptic adaptation of neural networks with
      hundreds of synaptic connections are proposed. The paper starts by introducing a
      linear approximate model for the temporal dynamics of synaptic transmission. The
      proposed linear model substantially simplifies the analysis and training of
      spiking neural networks. Furthermore, it is capable of replicating the synaptic
      response of the non-linear facilitation-depression model with an accuracy better
      than 92.5%. In the second part of the paper, a supervised spike-in-spike-out
      learning rule for synaptic adaptation in dynamic synapse neural networks (DSNN)
      is proposed. The proposed learning rule is a biologically plausible process, and
      it is capable of simultaneously adjusting both pre- and post-synaptic components
      of individual synapses. The last section of the paper starts with presenting the
      rigorous analysis of the learning algorithm in a system identification task with
      hundreds of synaptic connections which confirms the learning algorithm's
      accuracy, repeatability and scalability. The DSNN is utilized to predict the
      spiking activity of cortical neurons and pattern recognition tasks. The DSNN
      model is demonstrated to be a generative model capable of producing different
      cortical neuron spiking patterns and CA1 Pyramidal neurons recordings. A single
      layer DSNN classifier on a benchmark pattern recognition task outperforms a 2
      Layer Neural Network and GMM classifiers while having fewer numbers of free
      parameters and decides with a shorter observation of data. DSNN performance in
      the benchmark pattern recognition problem shows 96.7% accuracy in classifying
      three classes of spiking activity. 

PMID- 24867389
TI  - Multigene mutational profiling of cholangiocarcinomas identifies actionable
      molecular subgroups.
AB  - One-hundred-fifty-three biliary cancers, including 70 intrahepatic
      cholangiocarcinomas (ICC), 57 extrahepatic cholangiocarcinomas (ECC) and 26
      gallbladder carcinomas (GBC) were assessed for mutations in 56 genes using
      multigene next-generation sequencing. Expression of EGFR and mTOR pathway genes
      was investigated by immunohistochemistry. At least one mutated gene was observed
      in 118/153 (77%) cancers. The genes most frequently involved were KRAS (28%),
      TP53 (18%), ARID1A (12%), IDH1/2 (9%), PBRM1 (9%), BAP1 (7%), and PIK3CA (7%).
      IDH1/2 (p=0.0005) and BAP1 (p=0.0097) mutations were characteristic of ICC, while
      KRAS (p=0.0019) and TP53 (p=0.0019) were more frequent in ECC and GBC.
      Multivariate analysis identified tumour stage and TP53 mutations as independent
      predictors of survival. Alterations in chromatin remodeling genes (ARID1A, BAP1,
      PBRM1, SMARCB1) were seen in 31% of cases. Potentially actionable mutations were
      seen in 104/153 (68%) cancers: i) KRAS/NRAS/BRAF mutations were found in 34% of
      cancers; ii) mTOR pathway activation was documented by immunohistochemistry in
      51% of cases and by mutations in mTOR pathway genes in 19% of cancers; iii) TGF
      beta/Smad signaling was altered in 10.5% cancers; iv) mutations in tyrosine
      kinase receptors were found in 9% cases. Our study identified molecular subgroups
      of cholangiocarcinomas that can be explored for specific drug targeting in
      clinical trials. 

PMID- 24867392
TI  - Prevalence of COPD by disease severity in men and women in northern Vietnam.
AB  - The prevalence of COPD and its risk factor pattern varies between different areas
      of the world. The aim of this study was to investigate the prevalence of COPD by
      disease severity in men and women and risk factors for COPD in northern Vietnam.
      From all 5782 responders to a questionnaire survey, a randomly selected sample of
      1500 subjects was invited to a clinical follow-up study. The methods included a
      structured interview using a modified GA2LEN study questionnaire for registration
      of symptoms and possible determinants of disease. Spirometry was performed before
      and after bronchodilation. The age distribution of the sample was 23-72 years. Of
      684 subjects attending, 565 completed acceptable spirometric measurements. The
      prevalence of COPD defined by the GOLD criteria was 7.1%; in men 10.9% and in
      women 3.9% (p = 0.002). Of those 3.4% had a mild disease, 2.8% a moderate and
      0.9% a severe disease. In ages >50 years, 23.5% of men and 6.8% of women had
      COPD. Among smokers aged >60 years (all men), 47.8% had COPD. None of the women
      with COPD had been smokers. Increasing age, smoking and male sex were the
      dominating risk factors, although male sex lost its significance in a
      multivariate setting. The prevalence of COPD among adults in northern Vietnam was
      7.1% and was considerably higher among men than women. The prevalence increased
      considerably with age. Increasing age and smoking, the latter among men only,
      were the most important determinants of COPD.

PMID- 24867393
TI  - Early Brain Activity Relates to Subsequent Brain Growth in Premature Infants.
AB  - Recent experimental studies have shown that early brain activity is crucial for
      neuronal survival and the development of brain networks; however, it has been
      challenging to assess its role in the developing human brain. We employed serial
      quantitative magnetic resonance imaging to measure the rate of growth in
      circumscribed brain tissues from preterm to term age, and compared it with
      measures of electroencephalographic (EEG) activity during the first postnatal
      days by 2 different methods. EEG metrics of functional activity were computed:
      EEG signal peak-to-peak amplitude and the occurrence of developmentally important
      spontaneous activity transients (SATs). We found that an increased brain activity
      in the first postnatal days correlates with a faster growth of brain structures
      during subsequent months until term age. Total brain volume, and in particular
      subcortical gray matter volume, grew faster in babies with less cortical
      electrical quiescence and with more SAT events. The present findings are
      compatible with the idea that (1) early cortical network activity is important
      for brain growth, and that (2) objective measures may be devised to follow early
      human brain activity in a biologically reasoned way in future research as well as
      during intensive care treatment. 

PMID- 24867391
TI  - Long-term safety of perampanel and seizure outcomes in refractory partial-onset
      seizures and secondarily generalized seizures: results from phase III extension
      study 307.
AB  - OBJECTIVE: To evaluate safety, tolerability, seizure frequency, and regional
      variations in treatment responses with the AMPA antagonist, perampanel, in a
      large extension study during up to 3 years of treatment. METHODS: Patients >= 12
      years old with partial-onset seizures despite treatment with 1-3 antiepileptic
      drugs at baseline completed a perampanel phase III trial and entered extension
      study 307 (NCT00735397). Patients were titrated to 12 mg/day (or their individual
      maximum tolerated dose) during the blinded conversion period, followed by open
      label maintenance. Exposure, safety (adverse events [AEs], vital signs, weight,
      electrocardiography [ECG], laboratory values) and seizure outcomes were analyzed;
      key measures were assessed by geographic regions. RESULTS: Among 1,216 patients,
      median exposure was 1.5 years (range 1 week to 3.3 years), with >300 patients
      treated for >2 years. Treatment retention was 58.5% at cutoff. AEs reported in >=
      10% of patients were dizziness, somnolence, headache, fatigue, irritability, and
      weight increase. Only dizziness and irritability caused discontinuation in >1% of
      patients (3.9% and 1.3%, respectively). The only serious AEs reported in >1% of
      patients were epilepsy-related (convulsion, 3.0%; status epilepticus, 1.1%). No
      clinically relevant changes in vital signs, ECG or laboratory parameters were
      seen. After titration/conversion, responder rate and median percentage change
      from baseline in seizure frequency were stable: 46% for both measures at 9 months
      (in 980 patients with >= 9 months' exposure) and 58% and 60%, respectively, at 2
      years (in the 337 patients with 2 years' exposure). Median percentage reduction
      in frequency of secondarily generalized (SG) seizures ranged from 77% at 9 months
      (N = 422) to 90% at 2 years (N = 141). Among the 694 patients with maintenance
      data >= 1 year, 5.3% were seizure-free for the entire year. SIGNIFICANCE: No new
      safety signals emerged during up to 3 years of perampanel exposure in 39
      countries. Seizure responses remained stable, with marked reductions,
      particularly in SG seizures.

PMID- 24867394
TI  - Idiopathic pulmonary fibrosis: evolving concepts.
AB  - Idiopathic pulmonary fibrosis (IPF) occurs predominantly in middle-aged and older
      adults and accounts for 20% to 30% of interstitial lung diseases. It is usually
      progressive, resulting in respiratory failure and death. Diagnostic criteria for
      IPF have evolved over the years, and IPF is currently defined as a disease
      characterized by the histopathologic pattern of usual interstitial pneumonia
      occurring in the absence of an identifiable cause of lung injury. Understanding
      of the pathogenesis of IPF has shifted away from chronic inflammation and toward
      dysregulated fibroproliferative repair in response to alveolar epithelial injury.
      Idiopathic pulmonary fibrosis is likely a heterogeneous disorder caused by
      various interactions between genetic components and environmental exposures. High
      resolution computed tomography can be diagnostic in the presence of typical
      findings such as bilateral reticular opacities associated with traction
      bronchiectasis/bronchiolectasis in a predominantly basal and subpleural
      distribution, along with subpleural honeycombing. In other circumstances, a
      surgical lung biopsy may be needed. The clinical course of IPF can be
      unpredictable and may be punctuated by acute deteriorations (acute exacerbation).
      Although progress continues in unraveling the mechanisms of IPF, effective
      therapy has remained elusive. Thus, clinicians and patients need to reach
      informed decisions regarding management options including lung transplant. The
      findings in this review were based on a literature search of PubMed using the
      search terms idiopathic pulmonary fibrosis and usual interstitial pneumonia,
      limited to human studies in the English language published from January 1, 2000,
      through December 31, 2013, and supplemented by key references published before
      the year 2000.

PMID- 24867395
TI  - The consequences of chronic kidney disease mislabeling in living kidney donors.
AB  - Despite numerous studies that substantiate its long-term safety, barriers to
      kidney donation persist. These include issues of insurability after donation and
      its consequent financial and emotional burdens. We present 2 cases in which
      mislabeling of kidney donors as having chronic kidney disease shortly after
      kidney donation adversely affected their insurability. A concerted effort should
      be made to affect public policy such that insurability and the psychosocial well
      being of living donors are protected. 

PMID- 24867396
TI  - Controversies in Barrett esophagus.
AB  - Barrett esophagus develops when metaplastic columnar epithelium predisposed to
      develop adenocarcinoma replaces esophageal squamous epithelium damaged by
      gastroesophageal reflux disease. Although several types of columnar metaplasia
      have been described in Barrett esophagus, intestinal metaplasia with goblet cells
      currently is required for a definitive diagnosis in the United States. Studies
      indicate that the risk of adenocarcinoma for patients with nondysplastic Barrett
      esophagus is only 0.12% to 0.38% per year, which is substantially lower than
      previous studies had suggested. Nevertheless, the incidence of esophageal
      adenocarcinoma continues to rise at an alarming rate. Regular endoscopic
      surveillance for dysplasia is the currently recommended cancer prevention
      strategy for Barrett esophagus, but a high-quality study has found no benefit of
      surveillance in preventing deaths from esophageal cancer. Medical societies
      currently recommend endoscopic screening for Barrett esophagus in patients with
      multiple risk factors for esophageal adenocarcinoma, including chronic
      gastroesophageal reflux disease, age of 50 years or older, male sex, white race,
      hiatal hernia, and intra-abdominal body fat distribution. However, because the
      goal of screening is to identify patients with Barrett esophagus who will benefit
      from endoscopic surveillance and because such surveillance may not be beneficial,
      the rationale for screening might be made on the basis of faulty assumptions.
      Endoscopic ablation of dysplastic Barrett metaplasia has been reported to prevent
      its progression to cancer, but the efficacy of endoscopic eradication of
      nondysplastic Barrett metaplasia as a cancer preventive procedure is highly
      questionable. This review discusses some of these controversies that affect the
      physicians and surgeons who treat patients with Barrett esophagus. Studies
      relevant to controversial issues in Barrett esophagus were identified using
      PubMed and relevant search terms, including Barrett esophagus, ablation,
      dysplasia, radiofrequency ablation, and endoscopic mucosal resection. 

PMID- 24867397
TI  - My treatment approach to chronic hepatitis C virus.
AB  - The treatment of chronic hepatitis C virus (HCV) is evolving rapidly. In 2014,
      the standard of care and new backbone of HCV treatment is the polymerase
      inhibitor sofosbuvir (SOF). Our treatment approach in patients with HCV genotype
      1 is 12 weeks of SOF, peginterferon (PEGINF), and ribavirin (RBV). In patients
      with cirrhosis or extrahepatic manifestations of HCV who cannot tolerate PEGINF,
      we use 12 weeks of SOF and simeprevir. The latter is less costly and more
      effective than SOF and RBV for 24 weeks. Our treatment approach in all patients
      with genotype 2 is SOF and RBV for 12 weeks. Hepatitis C virus genotype 3 is now
      the most costly and difficult to cure. Our approach to treatment-naive patients
      with genotype 3 is SOF and RBV for 24 weeks. In patients who have previously
      undergone PEGINF and RBV treatment, we use PEGINF, SOF, and RBV for 12 weeks,
      which is equally if not more effective and less costly than SOF and RBV for 24
      weeks. Patients with cirrhosis who cannot tolerate PEGINF should be treated for
      24 weeks with SOF and RBV, although the sustained virologic response is
      suboptimal. 

PMID- 24867398
TI  - Cost considerations in the treatment of anal fissures.
AB  - Anal fissure is a split in the lining of the distal anal canal. Lateral internal
      sphincterotomy remains the gold standard for treatment of anal fissure. Although
      technique is simple and effective, a drawback of this surgical procedure is its
      potential to cause minor but some times permanent alteration in rectal
      continence. Conservative approaches (such as topical application of ointment or
      botulinum toxin injections) have been proposed in order to treat this condition
      without any risk of permanent injury of the internal anal sphincter. These
      treatments are effective in a large number of patients. Furthermore, with the
      ready availability of medical therapies to induce healing of anal fissure, the
      risk of a first-line surgical approach is difficult to justify. The conservative
      treatments have a lower cost than surgery. Moreover, evaluation of the actual
      costs of each therapeutic option is important especially in times of economic
      crisis and downsizing of health spending. 

PMID- 24867399
TI  - Highly efficient and flexible electrospun carbon-silica nanofibrous membrane for
      ultrafast gravity-driven oil-water separation.
AB  - A novel free-standing and flexible electrospun carbon-silica composite
      nanofibrous membrane is newly introduced. The characterization results suggest
      that the electrospun composite nanofibers are constructed by carbon chains
      interpenetrated through a linear network of 3-dimensional SiO2. Thermogravimetric
      analysis indicates that the presence of insulating silica further improve the
      thermal resistance of the membrane. Additionally, the mechanical strength test
      shows that the membrane's toughness and flexibility can be enhanced if the
      concentration of SiO2 is maintained below 2.7 wt %. Thermal and chemical
      stability test show that the membrane's wettability properties can be sustained
      at an elevated temperature up to 300  degrees C and no discernible change in
      wettability was observed under highly acidic and basic conditions. After surface
      coating with silicone oil for 30 mins, the composite membrane exhibits ultra
      hydrophobic and superoleophilic properties with water and oil contact angles
      being 144.2 +/- 1.2 degrees  and 0 degrees , respectively. The enhanced
      flexibility and selective wetting property enables the membrane to serve as an
      effective substrate for separating free oil from water. Lab-scale oil-water
      separation test indicates that the membrane possesses excellent oil-water
      separation efficiency. In addition, its inherent property of high porosity allows
      oil-water separation to be performed in a gravity-driven process with high-flux.
      We anticipate that this study will open up a new avenue for fabrication of free
      standing carbonaceous composite membrane with tunable flexibility for energy
      efficient and high-throughput production of clean water. 

PMID- 24867400
TI  - Transition metal-mediated bioorthogonal protein chemistry in living cells.
AB  - Considerable attention has been focused on improving the biocompatibility of
      Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC), a hallmark of bioorthogonal
      reaction, in living cells. Besides creating copper-free versions of click
      chemistry such as strain promoted azide-alkyne cycloaddition (SPAAC), a central
      effort has also been made to develop various Cu(I) ligands that can prevent the
      cytotoxicity of Cu(I) ions while accelerating the CuAAC reaction. Meanwhile,
      additional transition metals such as palladium have been explored as alternative
      sources to promote a bioorthogonal conjugation reaction on cell surface, as well
      as within an intracellular environment. Furthermore, transition metal mediated
      chemical conversions beyond conjugation have also been utilized to manipulate
      protein activity within living systems. We highlight these emerging examples that
      significantly enriched our protein chemistry toolkit, which will likely expand
      our view on the definition and applications of bioorthogonal chemistry.

PMID- 24867403
TI  - The discovery of Polo-like kinase 4 inhibitors: design and optimization of
      spiro[cyclopropane-1,3?'[3H]indol]-2'(1'H).ones as orally bioavailable antitumor
      agents.
AB  - Polo-like kinase 4 (PLK4), a unique member of the polo-like kinase family of
      serine-threonine kinases, is a master regulator of centriole duplication that is
      important for maintaining genome integrity. Overexpression of PLK4 is found in
      several human cancers and is linked with a predisposition to tumorigenesis.
      Previous efforts to identify potent and efficacious PLK4 inhibitors resulted in
      the discovery of (E)-3-((1H-indazol-6-yl)methylene)indolin-2-ones, which are
      superseded by the bioisosteric 2-(1H-indazol-6-yl)spiro[cyclopropane-1,3'
      indolin]-2'-ones reported herein. Optimization of this new cyclopropane-linked
      series was based on a computational model of a PLK4 X-ray structure and SAR
      attained from the analogous alkenelinked series. The racemic cyclopropane-linked
      compounds showed PLK4 affinity and antiproliferative activity comparable to their
      alkene-linked congeners with improved hysicochemical, ADME, and pharmacokinetic
      properties. Positive xenograft results from the MDA-MB-468 human breast cancer
      xenograft model for compound 18 support the investigation of PLK4 inhibitors as
      anticancer therapeutics. A PLK4 X-ray co-structure with racemate 18 revealed
      preferential binding of the 1R,2S enantiomer to the PLK4 kinase domain.

PMID- 24867405
TI  - The role of dural sinus stenosis in idiopathic intracranial hypertension
      pathogenesis: the self-limiting venous collapse feedback-loop model.
AB  - In recent years the efficacy of endovascular venous stenting in idiopathic IIH
      treatment has been consistently reported, strongly suggesting that sinus stenosis
      should be viewed as a causative factor rather than a secondary phenomenon. We
      propose that in subjects carrying one or more collapsible segments of large
      cerebral venous collectors and exposed to a number of different promoting
      factors, sinus venous compression and cerebrospinal fluid (CSF) hypertension may
      influence each other in a circular way, leading to a new relatively stable
      venous/CSF pressures balance state at higher values. The mechanism relay on self
      limiting venous collapse (SVC) feedback-loop between the CSF pressure, that
      compresses the sinus, and the consequent venous pressure rise, that increases the
      CSF pressure. The result is the "coupled" increase of both pressure values, a
      phenomenon not expected in presence of sufficiently rigid central veins. Once the
      maximum stretch of venous wall is reached the loop stabilize at higher venous/CSF
      pressure values and become self-sustaining, therefore persisting even after the
      ceasing of the promoting factor. Notably, the SVC is reversible provided an
      adequate perturbation is carried to whichever side of the loop such as sinus
      venous stenting, on one hand, and CSF diversion or even a single CSF withdrawal
      by lumbar puncture (LP), on the other. The SVC model predicts that any condition
      leading to an increase of either, cerebral venous pressure or CSF pressure may
      trigger the feedback loop in predisposed individuals. Migraine with and without
      aura, a disease sharing with IIH a much higher prevalence among women of
      childbearing age, is associated with waves of significant brain hyperperfusion.
      These may lead to the congestion of large cerebral venous collectors and could
      represent a common SVC promoting condition in susceptible individuals. The SVC
      model give reason of the high specificity and sensitivity of sinus stenosis as
      IIH predictor and of the multiplicity of the factors that have been found
      associated with IIH. Moreover it might explain why, among the sinus stenosis
      carriers, young and overweight women are at higher risk of developing the
      disease. Finally, the SVC model fully explain the enigmatic longstanding
      remissions that can be commonly observed after a single LP with CSF subtraction
      in IIH with or without papilledema. 

PMID- 24867404
TI  - A simple and effective method for high quality co-extraction of genomic DNA and
      total RNA from low biomass Ectocarpus siliculosus, the model brown alga.
AB  - The brown seaweed Ectocarpus siliculosus is an emerging model species distributed
      worldwide in temperate coastal ecosystems. Over 1500 strains of E. siliculosus
      are available in culture from a broad range of geographic locations and
      ecological niches. To elucidate the molecular mechanisms underlying its capacity
      to cope with different environmental and biotic stressors, genomic and
      transcriptomic studies are necessary; this requires the co-isolation of genomic
      DNA and total RNA. In brown algae, extraction of nucleic acids is hindered by
      high concentrations of secondary metabolites that co-precipitate with nucleic
      acids. Here, we propose a reliable, rapid and cost-effective procedure for the co
      isolation of high-quality nucleic acids using small quantities of biomass (25-,
      50- and 100 mg) from strains of E. siliculosus (RHO12; LIA4A; EC524 and REP10-11)
      isolated from sites with different environmental conditions. The procedure
      employs a high pH extraction buffer (pH 9.5) which contains 100 mM Tris-HCl and
      150 mM NaCl, with the addition of 5 mM DTT and 1% sarkosyl to ensure maximum
      solubility of nucleic acids, effective inhibition of nuclease activity and
      removal of interfering contaminants (e.g. polysaccharides, polyphenols). The use
      of sodium acetate together with isopropanol shortened precipitation time and
      enhanced the yields of DNA/RNA. A phenol:chlorophorm:isoamyl alcohol step was
      subsequently used to purify the nucleic acids. The present protocol produces high
      yields of nucleic acids from only 25 mg of fresh algal biomass (0.195 and 0.284
      ug mg(-1) fresh weigh of RNA and DNA, respectively) and the high quality of the
      extracted nucleic acids was confirmed through spectrophotometric and
      electrophoretic analyses. The isolated RNA can be used directly in downstream
      applications such as RT-PCR and the genomic DNA was suitable for PCR, producing
      reliable restriction enzyme digestion patterns. Co-isolation of DNA/RNA from
      different strains indicates that this method is likely to have wider applications
      for intra- and inter-specific studies on other brown algae.

PMID- 24867402
TI  - Development, calibration and performance of an HIV transmission model
      incorporating natural history and behavioral patterns: application in South
      Africa.
AB  - Understanding HIV transmission dynamics is critical to estimating the potential
      population-wide impact of HIV prevention and treatment interventions. We
      developed an individual-based simulation model of the heterosexual HIV epidemic
      in South Africa and linked it to the previously published Cost-Effectiveness of
      Preventing AIDS Complications (CEPAC) International Model, which simulates the
      natural history and treatment of HIV. In this new model, the CEPAC Dynamic Model
      (CDM), the probability of HIV transmission per sexual encounter between short
      term, long-term and commercial sex worker partners depends upon the HIV RNA and
      disease stage of the infected partner, condom use, and the circumcision status of
      the uninfected male partner. We included behavioral, demographic and biological
      values in the CDM and calibrated to HIV prevalence in South Africa pre
      antiretroviral therapy. Using a multi-step fitting procedure based on Bayesian
      melding methodology, we performed 264,225 simulations of the HIV epidemic in
      South Africa and identified 3,750 parameter sets that created an epidemic and had
      behavioral characteristics representative of a South African population pre-ART.
      Of these parameter sets, 564 contributed 90% of the likelihood weight to the fit,
      and closely reproduced the UNAIDS HIV prevalence curve in South Africa from 1990
      2002. The calibration was sensitive to changes in the rate of formation of short
      duration partnerships and to the partnership acquisition rate among high-risk
      individuals, both of which impacted concurrency. Runs that closely fit to
      historical HIV prevalence reflect diverse ranges for individual parameter values
      and predict a wide range of possible steady-state prevalence in the absence of
      interventions, illustrating the value of the calibration procedure and utility of
      the model for evaluating interventions. This model, which includes detailed
      behavioral patterns and HIV natural history, closely fits HIV prevalence
      estimates. 

PMID- 24867407
TI  - Potential drug interactions in travelers with chronic illnesses: a large
      retrospective cohort study.
AB  - BACKGROUND: Data regarding the prevalence of potential interactions between
      travel-related medications (TRM) and chronic medications in use, or medical
      conditions of travelers to developing countries are limited. METHODS: A
      retrospective cohort study of travelers to low income countries. We extracted
      data on demographics, travel destinations, use of chronic medications, drug
      allergies, and relevant medical conditions. The following TRM were evaluated:
      mefloquine, primaquine, doxycycline, atovaquone/proguanil, fluoroquinolone
      antibiotics, rifaximin, azithromycin, and acetazolamide. RESULTS: A total of
      16,263 travelers were included in the analysis, of whom 3299(20%) suffered from
      chronic illnesses and 2316(14%) reported chronic medication use. A potential drug
      drug interaction with TRM was identified in 1047(45%) of travelers using chronic
      medication. Fluoroquinolones and azithromycin were the most commonly implicated
      TRMs. A potential medical condition interaction with TRM was identified in
      717(22%) of travelers having chronic illnesses. acetazolamide, primaquine and
      mefloquine, were the most commonly TRMs implicated. Drug allergies, which can
      pose a relative contraindication for use of acetazolamide, were reported by
      1323(8.1%) of all travelers. CONCLUSIONS: Potential drug-drug and drug-disease
      interactions involving TRM might occur in a significant proportion of travelers
      with chronic medical conditions. Education of health practitioners regarding such
      potential drug interactions and caution when in prescribing travel-related
      medications is warranted.

PMID- 24867409
TI  - Interaction of divalent metal ions with the carboxyl-terminal domain of human
      voltage-gated proton channel Hv1.
AB  - The voltage-gated proton channel Hv1 functions as a dimer, in which the
      intracellular C-terminal domain of the protein is responsible for the dimeric
      architecture and regulates proton permeability. Although it is well known that
      divalent metal ions have effect on the proton channel activity, the interaction
      of divalent metal ions with the channel in detail is not well elucidated. Herein,
      we investigated the interaction of divalent metal ions with the C-terminal domain
      of human Hv1 by CD spectra and fluorescence spectroscopy. The divalent metal ions
      binding induced an obvious conformational change at pH 7 and a pH-sensitive
      reduction of thermostability in the C-terminal domain. The interactions were
      further estimated by fluorescence spectroscopy experiments. There are at least
      two binding sites for divalent metal ions binding to the C-terminal domain of
      Hv1, either of which is close to His(244) or His(266) residue. The binding of
      Zn(2+) to the two sites both enhanced the fluorescence of the protein at pH 7,
      whereas the binding of other divalent metal ions to the two sites all resulted
      fluorescence quenching. The orders of the strength of divalent metal ions binding
      to the two sites from strong to weak are both Co(2+), Ca(2+), Ni(2+), Mg(2+), and
      Mn(2+). The strength of Ca(2+), Co(2+), Mg(2+), Mn(2+) and Ni(2+) binding to the
      site close to His(244) is stronger than that of these divalent metal ions binding
      to the site close to His(266). 

PMID- 24867408
TI  - Inhibition of intestinal polyp growth by oral ingestion of bovine lactoferrin and
      immune cells in the large intestine.
AB  - Studies using animal models have demonstrated that ingestion of bovine
      lactoferrin (bLF) inhibits carcinogenesis in the colon and other organs of
      experimental animals. As a result of these studies, a blinded, randomized,
      controlled clinical trial was conducted in the National Cancer Center Hospital,
      Tokyo, Japan to determine whether ingestion of bLF had an effect on the growth of
      colorectal polyps in humans. Patients with colorectal polyps <=5 mm diameter and
      likely to be adenomas ingested 0, 1.5, or 3.0 g bLF daily for 1 year. Ingestion
      of 3.0 g bLF suppressed the growth of colorectal polyps and increased the level
      of serum human lactoferrin in trial participants 63 years old or younger. The
      purpose of the present study was to investigate correlations between immune
      parameters and changes in polyp size. Trial participants with regressing polyps
      had increased NK cell activity, increased serum hLF levels (indicating increased
      neutrophil activity), and increased numbers of CD4+ cells in the polyps. These
      findings are consistent with a correlation between higher immune activity and
      suppression of colorectal polyps. In addition, participants with regressing
      polyps had lower numbers of PMNs and increased numbers of S100A8+ cells in the
      polyps, consistent with a correlation between lower inflammatory potential in the
      colon and suppression of colorectal polyps. Trial participants ingesting bLF had
      increased serum hLF levels, a possible increase in systemic NK cell activity, and
      increased numbers of CD4+ and CD161+ cells in the polyps. Taken together, our
      findings suggest that bLF suppressed colorectal polyps by enhancing immune
      responsiveness. 

PMID- 24867410
TI  - Tri-isopropylsilyl thioglycosides as masked glycosyl thiol nucleophiles for the
      synthesis of S-linked glycosides and glyco-conjugates.
AB  - Tri-isopropylsilyl thio-glycosides (TIPS S-glycosides) were synthesized through
      base promoted SN2 substitution of glycosyl halides with TIPS-SH or by Lewis acid
      promoted glycosylation of TIPS-SH with glycosyl acetates or p-methoxyphenyl
      glycosides. Various thioglycoside derivatives were obtained in high yields by one
      pot fluoride-mediated de-silylation and thiol alkylation with alkyl halides or
      Michael acceptors of one common TIPS S-glycoside. 

PMID- 24867411
TI  - Evaluation of polycaprolactone matrices for sustained vaginal delivery of
      nevirapine in the prevention of heterosexual HIV transmission.
AB  - Nevirapine (NVP) was loaded in polycaprolactone (PCL) matrices to produce vaginal
      inserts with the aim of preventing HIV transmission. NVP dispersions in PCL were
      prepared, at 10% (w/w) theoretical loading, measured with respect to the PCL
      content of the matrices, in the form of (1) NVP only, (2) a physical mixture of
      NVP with polyethylene glycol (PEG) 6000 or (c) a solid dispersion (SD) with PEG
      produced by co-dissolution in ethanol. Characterisation of SD by differential
      scanning calorimetry and attenuated total reflectance-Fourier transform infrared
      spectroscopy suggested transformation of the crystalline structure of NVP to an
      amorphous form which consequently increased the dissolution rate of drug. A low
      loading efficiency of 13% was obtained for NVP-loaded matrices and less than 20%
      for matrices prepared using physical mixtures of drug and PEG. The loading
      efficiency was improved significantly to around 40% when a 1:4 NVP-PEG SD was
      used for matrix production. After 30 days, 40% of the drug content was released
      from NVP-loaded matrices, 55% from matrices containing 1:4 NVP-PEG physical
      mixtures and 60% from matrices loaded with 1:4 NVP-PEG SDs. The in vitro anti
      viral activity of released NVP was assessed using a luciferase reporter gene
      assay following the infection of HeLa cells with pseudo-typed HIV-1. NVP released
      from PCL matrices in simulated vaginal fluid retained over 75% anti-HIV activity
      compared with the non-formulated NVP control. In conclusion, 1:4 NVP-PEG SDs when
      loaded in PCL matrices increase drug loading efficiency and improve release
      behaviour.

PMID- 24867412
TI  - Perinatal outcome in cases of isolated single umbilical artery and its effects on
      neonatal cord blood gas indices.
AB  - Abstract We aimed to evaluate perinatal outcomes and blood gas indices of
      isolated single umbilical artery (SUA). In this retrospective study, 134 fetuses
      with SUA were evaluated. A total of 77 (57.4%) fetuses with isolated SUA (iSUA)
      were compared with maternal age-matched 95 fetuses with double umbilical arteries
      (DUA), with respect to pregnancy outcome and umbilical cord blood gas indices.
      The incidence of SUA in our cohort was 1.04%. Patients with iSUA had lower
      neonatal birth weight compared with the control group (2,635 +/- 972 g vs 2,991
      +/- 669 g; p = 0.009). Small for gestational age (SGA) frequency was higher in
      the group of iSUA when compared with fetuses with DUA (17.4% vs 5.4%; p = 0.03).
      Regarding the umbilical cord blood gas, the parameters were comparable between
      the two groups. SUA has a favourable obstetric outcome as long as the
      accompanying malformations are ruled out. Furthermore, neonatal cord blood gas
      parameters in fetuses with iSUA do not differ from fetuses with DUA. 

PMID- 24867413
TI  - An unusual complication of crawford tube insertion.
AB  - The authors describe an unusual and challenging complication of bicanalicular
      (Crawford) stent insertion that has previously never been reported. A 27-year-old
      man sustained multiple lacerations to the left (L) periocular and facial areas
      with a glass bottle. He was admitted under the care of the Plastic Surgical team
      at another institution and underwent repair of the facial, eyelid, and
      canalicular lacerations in the operating room. During the surgery, a Crawford
      stylet was guided in the L inferior canaliculus but was not retrieved nasally.
      Neuroimaging revealed that the metallic stylet of the Crawford tube was within
      the orbit, extending via the superior orbital fissure into the middle cranial
      fossa. The patient was then transferred under the care of the neurosurgical team
      and underwent a combined orbital/neurosurgical procedure to retrieve the stylet. 

PMID- 24867414
TI  - Imaging findings of recurrent tumors after orbital exenteration and free flap
      reconstruction.
AB  - PURPOSE: Tumors that recur following orbital exenteration may not be evident on
      clinical examination, highlighting the need for imaging surveillance. The goal of
      this study was to report the imaging characteristics of recurrent tumors
      following orbital exenteration and free flap reconstruction. METHODS: The authors
      retrospectively reviewed the records of 48 patients who underwent orbital
      exenteration for the treatment of orbital malignancy and identified 17 recurrent
      tumors in 17 patients. The lesions were assessed for the presence of a soft
      tissue mass, imaging characteristics, and fluorodeoxyglucose avidity. RESULTS:
      The recurrent tumors were detected 1 month to 6 years 10 months (median, 1 year 3
      month) after orbital exenteration. On both CT and MRI, all 17 lesions were soft
      tissue masses at presentation. On CT, the lesions demonstrated heterogeneous to
      homogeneous to centrally necrotic enhancement; on MRI, the lesions were T1
      hypointense to isointense and T2 hypointense to hyperintense. Twelve of the 15
      recurrent tumors with available preoperative imaging had an enhancing appearance
      similar to that of the original tumor. Thirteen of the 17 recurrent tumors were
      at the margin of a flap placed for reconstruction; the other 4 lesions were
      remote from the operative site. CONCLUSION: Recurrent tumors following orbital
      exenteration and free flap reconstruction demonstrate a wide range of imaging
      appearances but most often appear as a soft tissue masses often similar in
      appearance to the primary tumor and arising near the flap margin. Awareness of
      the imaging features of recurrent disease is important because failure to
      diagnose recurrence can delay appropriate treatment.

PMID- 24867416
TI  - A Quasi-Experimental Evaluation of High-Intensity Inpatient Sex Offender
      Treatment in the Netherlands.
AB  - The current study quasi-experimentally assessed the outcome of high-intensity
      inpatient sex offender treatment in the Netherlands in terms of sexual and
      violent (including sexual) recidivism. It was hypothesized that treated sex
      offenders would show lower recidivism rates than untreated sex offenders of the
      same risk level. In line with the risk principle of the Risk, Need, Responsivity
      (RNR) model, we predicted that this would especially hold true for offenders of
      higher risk levels. The study sample consisted of 25% of all convicted Dutch sex
      offenders not referred to any form of treatment and discharged from prison
      between 1996 and 2002, and all convicted Dutch sex offenders referred to
      inpatient treatment who were discharged between 1996 and 2002. Static-99R risk
      levels of these 266 offenders were retrospectively assessed and survival curves
      regarding sexual and violent (including sexual) recidivism were compared between
      treated and untreated offenders, controlling for level of risk. Mean follow-up
      was 148.0 months (SD = 29.6) and the base rate of sexual recidivism was 15.0% and
      38.4% for violent (including sexual) recidivism. Cox regression survival analyses
      showed marginally significant lower failure rates regarding sexual recidivism for
      treated high-risk offenders only, and significantly lower failure rates regarding
      violent (including sexual recidivism) for treated sex offenders of moderate-high
      and high-risk levels. No treatment effects for low and low-moderate risk
      offenders were found. Results underscore the risk principle of the RNR model:
      Treatment is more effective when its dosage is attuned to risk level. 

PMID- 24867417
TI  - Exploring Client and Therapist Experiences of Sexual Offender Intervention:
      Developing a Model of "Significant Events".
AB  - This research explored the therapeutic events both clients and therapists from
      community-based treatment interventions for perpetrators of sexual abuse identify
      as significant in their experience of psychological therapy. A qualitative design
      was utilized to address this research objective. The sample for the present
      research is comprised of three different treatment programs for sexual offending.
      Twenty-five clients and nine therapists participated in the study. Two
      qualitative measures were used to elicit client and therapist responses.
      Significant Aspects of Therapy Form was administered every second treatment
      session during each intervention program. The Significant Aspects Follow-Up
      Interview was conducted with a sub-sample of participants at the conclusion of
      each treatment module. Thematic analysis was used to identify significant themes
      noted by clients and therapists from forms and interviews. Thematic analysis
      resulted in a model of significant events in therapy. In this model, significant
      events were categorized into six domains. The six domains were as follows: (a)
      the process of therapy, (b) making changes and progress in therapy, (c) content
      and structure of therapy, (d) therapist contributions, (e) negative contributions
      to therapy, and (f) other factors Each domain further contained between 6 and 18
      themes, which are also reported. This study found much overlap and similarity in
      the experiences of therapy between clients of sexual offender therapy and general
      psychotherapy. Furthermore, there is overlap between therapists and clients in
      the aspects of therapy they identify as significant. The implications of these
      findings on effective service development and comprehensive service evaluations
      are discussed. 

PMID- 24867419
TI  - Recent advances in the oral delivery of insulin.
AB  - Insulin was discovered over 90 years ago. However oral insulin still remains a
      challenging and elusive goal. Extensive efforts are being made worldwide for
      developing noninvasive drug delivery systems, mainly via oral route as it is the
      most widely accepted means of administration. The main barriers faced in oral
      protein delivery are the enzymatic degradation and poor permeability across the
      intestinal wall. The approaches for developing an oral insulin delivery system
      mainly focus on overcoming these barriers. To overcome the gastro-intestinal
      barriers various types of formulations such as insulin conjugates, permeation
      enhancers, micro/nanoparticles, liposomes etc. are investigated. In the recent
      years a number of advances have taken place in understanding the needs and
      workable mechanisms of improved oral peptide delivery systems. In this review the
      recent patents on oral insulin is focused. Emphasis is on the technologies based
      on permeation enhancers and nanoparticle based carrier systems. 

PMID- 24867418
TI  - Improved results in paediatric diabetes care using a quality registry in an
      improvement collaborative: a case study in Sweden.
AB  - BACKGROUND: Several studies show that good metabolic control is important for
      children and adolescents with type 1 diabetes. In Sweden, there are large
      differences in mean haemoglobin A1c (HbA1c) in different hospitals and
      difficulties implementing national guidelines in everyday practice. This study
      shows how the participation in an improvement collaborative could facilitate
      improvements in the quality of care by paediatric diabetes teams. The Swedish
      paediatric diabetes quality registry, SWEDIABKIDS was used as a tool and resource
      for feedback and outcome measures. METHODS: Twelve teams at paediatric diabetes
      centres, caring for 30% (2302/7660) of patients in Sweden, participated in an 18
      month quality improvement program. Each team defined treatment targets, areas
      needing improvement, and action plans. The main outcome was the centre patients'
      mean HbA1c levels, but other clinical variables and change concepts were also
      studied. Data from the previous six months were compared with the first six
      months after starting the program, and the long-term follow up after another
      eleven months. RESULTS: All centres reduced mean HbA1c during the second and
      third periods compared with the first. The mean reduction for all was 3.7
      mmol/mol (p<0.001), compared with non-participating centres who improved their
      mean HbA1c with 1.7 mmol/mol during the same period. Many of the participating
      centres reduced the frequency of severe hypoglycaemia and/or ketoacidosis, and
      five centres reached their goal of ensuring that all patients had some sort of
      physical activity at least once weekly. Change concepts were, for example,
      improved guidelines, appointment planning, informing the patients, improving
      teamwork and active use of the registry, and health promotion activities.
      CONCLUSIONS: By involving paediatric diabetes teams in a quality improvement
      collaborative together with access to a quality register, the quality of
      paediatric diabetes care can improve, thereby contributing to a reduced risk of
      late complications for children and adolescents with diabetes.

PMID- 24867420
TI  - The acoustic features of inhalation can be used to quantify aerosol delivery from
      a DiskusTM dry powder inhaler.
AB  - PURPOSE: Some patients are unable to generate the peak inspiratory flow rate
      (PIFR) necessary to de-agglomerate drug particles from dry powder inhalers
      (DPIs). In this study we tested the hypothesis that the acoustic parameters of an
      inhalation are related to the PIFR and hence reflect drug delivery. METHODS: A
      sensitivity analysis of the relationship of the acoustics of inhalation to
      simultaneously recorded airflow, in a cohort of volunteers (n = 92) was
      performed. The Next Generation Impactor (NGI) was used to assess in vitro drug
      delivery from salmeterol/fluticasone and salbutamol DiskusTM DPIs. Fine particle
      fraction, FPF, (<5 MUm) was measured at 30-90 l/min for 2-6 s and correlated with
      acoustically determined flow rate (IFRc). In pharmacokinetic studies using a
      salbutamol (200 MUg) DiskusTM, volunteers inhaled either at maximal or minimal
      effort on separate days. RESULTS: PIFRc was correlated with spirometrically
      determined values (R (2) = 0.88). In in vitro studies, FPF increased as both flow
      rate and inhalation duration increased for the salmeterol/fluticasone DiskusTM
      (Adjusted R (2) = 0.95) and was proportional to flow rate only for the salbutamol
      DiskusTM (Adjusted R (2) = 0.71). In pharmacokinetic studies, blood salbutamol
      levels measured at 20 min were significantly lower when PIFRc was less than 60
      l/min, p < 0.0001. CONCLUSION: Acoustically-determined PIFR is a suitable method
      for estimating drug delivery and for monitoring inhalation technique over time.

PMID- 24867421
TI  - EphA2 targeting pegylated nanocarrier drug delivery system for treatment of lung
      cancer.
AB  - PURPOSE: Evaluation of tumor targeting pegylated EphA2 peptide coated
      nanoparticles (ENDDs) of a novel anticancer agent DIM-C-pPhC6H5 (DIM-P) and
      Docetaxel (DOC) and investigate its antitumor activity and potential for
      treatment of lung cancer. METHODS: Nanoparticles were prepared with DIM-P and DOC
      (NDDs) using Nano-DeBEE. ENDDs were prepared by conjugating NDDs with 6His-PEG2K
      EphA2 peptide and characterized for physicochemical properties, binding assay,
      cytotoxicity, cellular uptake studies, drug release and pharmacokinetic
      parameters. Anti-tumor activity of ENDDs was evaluated using a metastatic H1650
      and orthotopic A549 tumor models in nude mice and tumor tissue were analyzed by
      RT-PCR and immunohistochemistry. RESULTS: Particle size and entrapment efficiency
      of ENDDs were 197 +/- 21 nm and 95 +/- 2%. ENDDs showed 32.5 +/- 3.5% more
      cellular uptake than NDDs in tumor cells. ENDDs showed 23 +/- 3% and 26 +/- 4%
      more tumor reduction compared to NDDs in metastatic and orthotopic tumor models,
      respectively. In-vivo imaging studies using the Care stream MX FX Pro system
      showed (p < 0.001) 40-60 fold higher flux for ENDDs compared to NDDs at tumor
      site. CONCLUSIONS: The results emanating from these studies demonstrate anti
      cancer potential of DIM-P and the role of ENDDs as effective tumor targeting drug
      delivery systems for lung cancer treatment.

PMID- 24867422
TI  - Modulating protein release profiles by incorporating hyaluronic acid into PLGA
      microparticles Via a spray dryer equipped with a 3-fluid nozzle.
AB  - PURPOSE: The purpose of this study was to modulate the release profiles of the
      model protein drug from spray dried poly(DL-lactic-co-glycolic acid) (PLGA)
      microparticles by incorporating hyaluronic acid (HA) in the formulation. METHODS:
      Bovine serum albumin (BSA)-loaded PLGA microparticles with or without HA were
      prepared using a spray dryer equipped with a 3-fluid nozzle. The effects of HA on
      the surface tension and the rheological behavior of the inner feed solution were
      investigated. The physicochemical properties of the resulting microparticles were
      characterized using scanning electron microscopy (SEM), laser diffraction (LD),
      confocal laser scanning microscopy (CLSM) and X-ray photoelectron spectroscopy
      (XPS). Circular dischoism (CD) was used to characterize conformational integrity
      of BSA released from the microparticles. RESULTS: Spherical microparticles with
      D50 of 5-10 MUm were obtained. Addition of HA in inner feed solutions increased
      the feed viscosity, but with no influence on the surface tension. All inner feed
      solutions showed non-Newtonian shear thinning behavior and the rheological
      properties were not time dependent. The CLSM and XPS analyses suggested a core
      shell like structure of the microparticles when HA was incorporated. The release
      profiles of BSA were extended and the initial burst releases were suppressed with
      an increase in HA in the microparticle formulations. In addition, HA seemed to
      protect BSA from degradation upon the spray-drying process. CONCLUSIONS: The
      present work demonstrates the potential of HA to modulate protein release profile
      from PLGA microparticle formulations produced via spray drying using 3-fluid
      nozzle.

PMID- 24867423
TI  - NanoXCT: a novel technique to probe the internal architecture of pharmaceutical
      particles.
AB  - PURPOSE: To demonstrate the novel application of nano X-ray computed tomography
      (NanoXCT) for visualizing and quantifying the internal structures of
      pharmaceutical particles. METHODS: An Xradia NanoXCT-100, which produces ultra
      high-resolution and non-destructive imaging that can be reconstructed in three
      dimensions (3D), was used to characterize several pharmaceutical particles.
      Depending on the particle size of the sample, NanoXCT was operated in Zernike
      Phase Contrast (ZPC) mode using either: 1) large field of view (LFOV), which has
      a two-dimensional (2D) spatial resolution of 172 nm; or 2) high resolution (HRES)
      that has a resolution of 43.7 nm. Various pharmaceutical particles with different
      physicochemical properties were investigated, including raw (2-hydroxypropyl)
      beta-cyclodextrin (HbetaCD), poly (lactic-co-glycolic) acid (PLGA)
      microparticles, and spray-dried particles that included smooth and nanomatrix
      bovine serum albumin (BSA), lipid-based carriers, and mannitol. RESULTS: Both raw
      HbetaCD and PLGA microparticles had a network of voids, whereas spray-dried
      smooth BSA and mannitol generally had a single void. Lipid-based carriers and
      nanomatrix BSA particles resulted in low quality images due to high noise-to
      signal ratio. The quantitative capabilities of NanoXCT were also demonstrated
      where spray-dried mannitol was found to have an average void volume of 0.117 +/-
      0.247 MUm(3) and average void-to-material percentage of 3.5%. The single PLGA
      particle had values of 1993 MUm(3) and 59.3%, respectively. CONCLUSIONS: This
      study reports the first series of non-destructive 3D visualizations of inhalable
      pharmaceutical particles. Overall, NanoXCT presents a powerful tool to dissect
      and observe the interior of pharmaceutical particles, including those of a
      respirable size.

PMID- 24867425
TI  - Prediction of drug distribution in rat and humans using an artificial neural
      networks ensemble and a PBPK model.
AB  - PURPOSE: To develop a QSAR model, based on calculated molecular descriptors and
      an Artificial Neural Networks Ensemble (ANNE), for the estimation of rat tissue
      to-blood partition coefficients (Kt:b), as well as the assessment of the
      applicability domain of the model and its utility in predicting the drug
      distribution in humans. METHODS: A total of 1460 individual Kt:b values (75%
      train and 25% validation), obtained in 13 different rat tissues were collected in
      the literature. A correlation between simple molecular descriptors for
      lipophilicity, ionization, size and hydrogen bonding capacity and Kt:b data was
      attempted by using an ANNE. RESULTS: Similar statistics were observed between the
      train and validation group of data with correlations, between the observed values
      and the predicted average ANNE values, of 0.909 and 0.896, respectively. A
      degradation of the correlations was observed for predicted values with high
      uncertainty, as judged by the standard deviations of the ANNE outputs. This was
      further observed when using the ANNE Kt:b values in a Physiologically based
      pharmacokinetic (PBPK) model for predicting the Human Volume of distribution of
      another 532 drugs. CONCLUSIONS: This model (available as a MS Excel(r) workbook
      in the Supporting material of this article) may be a valuable tool for prediction
      and simulation in early drug development, allowing the in silico estimation of
      rat Kt:b values for PBPK purposes and also indicating its applicability domain.

PMID- 24867426
TI  - Rapidly dissolvable microneedle patches for transdermal delivery of exenatide.
AB  - PURPOSE: To assess the feasibility of transdermal delivery of exenatide (EXT)
      using low-molecular-weight sodium hyaluronate (HA) dissolving microneedles (MNs)
      patches for type 2 diabetes mellitus therapy. METHODS: Micromold casting method
      was used to fabricate EXT-loaded dissolving MNs. The characteristics of prepared
      MNs including mechanical strength, in vitro/in vivo insertion capacity,
      dissolution profile and storage stability were then investigated. Finally, the in
      vivo pharmacokinetics and hypoglycemic effects were compared with traditional
      subcutaneous (SC) injection. RESULTS: EXT-loaded dissolving MNs made of HA
      possessed sufficient mechanical strength and the strength could be weakened as
      the water content increases. The EXT preserved its pharmacological activity
      during fabrication and one-month storage. With the aid of spring-operated
      applicator, dissolving MNs could be readily penetrated into the skin in vitro/in
      vivo, and then rapidly dissolved to release encapsulated drug within 2 min.
      Additionally, transepidermal water loss (TEWL) determinations showed that skin's
      barrier properties disrupted by MNs recovered within 10-12 h. Transdermal
      pharmacokinetics and antidiabetic effects studies demonstrated that fabricated
      EXT MNs induced comparable efficacy to SC injection. CONCLUSIONS: Our rapidly
      dissolving MNs patch appears to an excellent, painless alternative to
      conventional SC injection of EXT, and this minimally invasive device might also
      be suitable for other biotherapeutics.

PMID- 24867427
TI  - Pathological alpha-synuclein impairs adult-born granule cell development and
      functional integration in the olfactory bulb.
AB  - Although the role of noxious alpha-synuclein (alpha-SYN) in the degeneration of
      midbrain dopaminergic neurons and associated motor deficits of Parkinson's
      disease is recognized, its impact on non-motor brain circuits and related
      symptoms remains elusive. Through combining in vivo two-photon imaging with time
      coded labelling of neurons in the olfactory bulb of A30P alpha-SYN transgenic
      mice, we show impaired growth and branching of dendrites of adult-born granule
      cells (GCs), with reduced gain and plasticity of dendritic spines. The spine
      impairments are especially pronounced during the critical phase of integration of
      new neurons into existing circuits. Functionally, retarded dendritic expansion
      translates into reduced electrical capacitance with enhanced intrinsic
      excitability and responsiveness of GCs to depolarizing inputs, while the spine
      loss correlates with decreased frequency of AMPA-mediated miniature EPSCs.
      Changes described here are expected to interfere with the functional integration
      and survival of new GCs into bulbar networks, contributing towards olfactory
      deficits and related behavioural impairments. 

PMID- 24867428
TI  - PAS-cal: a generic recombinant peptide calibration standard for mass
      spectrometry.
AB  - We describe the design, preparation, and mass-spectrometric characterization of a
      new recombinant peptide calibration standard with uniform biophysical and
      ionization characteristics for mass spectrometry. "PAS-cal" is an artificial
      polypeptide concatamer of peptide cassettes with varying lengths, each composed
      of the three small, chemically stable amino acids Pro, Ala, and Ser, which are
      interspersed by Arg residues to allow site-specific cleavage with trypsin. PAS
      cal is expressed at high yields in Escherichia coli as a Small Ubiquitin-like
      MOdifier (SUMO) fusion protein, which is easily purified and allows isolation of
      the PAS-cal moiety after SUMO protease cleavage. Upon subsequent in situ
      treatment with trypsin, the PAS-cal polypeptide yields a set of four defined
      homogeneous peptides in the range from 2 to 8 kDa with equal mass spacing. ESI-MS
      analysis revealed a conveniently interpretable raw spectrum, which after
      deconvolution resulted in a very simple pattern of four peaks with similar
      ionization signals. MALDI-MS analysis of a PAS-cal peptide mixture comprising
      both the intact polypeptide and its tryptic fragments revealed not only the four
      standard peptides but also the singly and doubly charged states of the intact
      concatamer as well as di- and trimeric adduct ion species between the peptides,
      thus augmenting the observable m/z range. The advantageous properties of PAS-cal
      are most likely a result of the strongly hydrophilic and conformationally
      disordered PEG-like properties of the PAS sequences. Therefore, PAS-cal offers an
      inexpensive and versatile recombinant peptide calibration standard for mass
      spectrometry in protein/peptide bioanalytics and proteomics research, the
      composition of which may be further adapted to fit individual needs. 

PMID- 24867431
TI  - Focus in honor of Yinsheng Wang, recipient of the 2013 Biemann Medal.

PMID- 24867430
TI  - Studying the chemistry of cationized triacylglycerols using electrospray
      ionization mass spectrometry and density functional theory computations.
AB  - Analysis of triacylglycerols (TAGs), found as complex mixtures in living
      organisms, is typically accomplished using liquid chromatography, often coupled
      to mass spectrometry. TAGs, weak bases not protonated using electrospray
      ionization, are usually ionized by adduct formation with a cation, including
      those present in the solvent (e.g., Na(+)). There are relatively few reports on
      the binding of TAGs with cations or on the mechanisms by which cationized TAGs
      fragment. This work examines binding efficiencies, determined by mass
      spectrometry and computations, for the complexation of TAGs to a range of cations
      (Na(+), Li(+), K(+), Ag(+), NH4(+)). While most cations bind to oxygen, Ag(+)
      binding to unsaturation in the acid side chains is significant. The importance of
      dimer formation, [2TAG + M](+) was demonstrated using several different types of
      mass spectrometers. From breakdown curves, it became apparent that two or three
      acid side chains must be attached to glycerol for strong cationization. Possible
      mechanisms for fragmentation of lithiated TAGs were modeled by computations on
      tripropionylglycerol. Viable pathways were found for losses of neutral acids and
      lithium salts of acids from different positions on the glycerol moiety. Novel
      lactone structures were proposed for the loss of a neutral acid from one position
      of the glycerol moiety. These were studied further using triple-stage mass
      spectrometry (MS(3)). These lactones can account for all the major product ions
      in the MS(3) spectra in both this work and the literature, which should allow for
      new insights into the challenging analytical methods needed for naturally
      occurring TAGs.

PMID- 24867432
TI  - Covalent embedding of Ni2+/Fe3+ cyanometallate structures in silica by sol-gel
      processing.
AB  - Compound [Ni(AEAPTS)2]3[Fe(CN)6]2 (AEAPTS = N-(2-aminoethyl)-3
      aminopropyltrimethoxysilane), in which Ni(2+) and Fe(3+) ions are
      ferromagnetically coupled through cyano bridges, was prepared. Sol-gel processing
      of the AEAPTS derivative resulted in incorporation of the cyanometallate in
      silica. The obtained material is magnetically ordered below 22 K with an
      effective magnetic moment MUeff of 4.46 MUB at room temperature, a maximum of
      8.60 MUB at approximately 15 K and a narrow hysteresis at 2 K, with a saturation
      remanence of about 300 emu mol(-1) and a coercitivity of 0.03 T.

PMID- 24867433
TI  - Melatonin improves mitochondrial function in inguinal white adipose tissue of
      Zucker diabetic fatty rats.
AB  - Mitochondrial dysfunction in adipose tissue may contribute to obesity-related
      metabolic derangements such as type 2 diabetes mellitus (T2DM). Because
      mitochondria are a target for melatonin action, the goal of this study was to
      investigate the effects of melatonin on mitochondrial function in white (WAT) and
      beige inguinal adipose tissue of Zucker diabetic fatty (ZDF) rats, a model of
      obesity-related T2DM. In this experimental model, melatonin reduces obesity and
      improves the metabolic profile. At 6 wk of age, ZDF rats and lean littermates
      (ZL) were subdivided into two groups, each composed of four rats: control (C-ZDF
      and C-ZL) and treated with oral melatonin in the drinking water (10 mg/kg/day)
      for 6 wk (M-ZDF and M-ZL). After the treatment period, animals were sacrificed,
      tissues dissected, and mitochondrial function assessed in isolated organelles.
      Melatonin increased the respiratory control ratio (RCR) in mitochondria from
      white fat of both lean (by 26.5%, P < 0.01) and obese (by 34.5%, P < 0.01) rats
      mainly through a reduction of proton leaking component of respiration (state 4)
      (28% decrease in ZL, P < 0.01 and 35% in ZDF, P < 0.01). However, melatonin
      treatment lowered the RCR in beige mitochondria of both lean (by 7%, P < 0.05)
      and obese (by 13%, P < 0.05) rats by maintaining high rates of uncoupled
      respiration. Melatonin also lowered mitochondrial oxidative status by reducing
      nitrite levels and by increasing superoxide dismutase activity. Moreover,
      melatonin treatment also caused a profound inhibition of Ca-induced opening of
      mPTP in isolated mitochondria from both types of fat, white and beige, in both
      lean and obese rats. These results demonstrate that chronic oral melatonin
      improves mitochondrial respiration and reduces the oxidative status and
      susceptibility to apoptosis in white and beige adipocytes. These melatonin
      effects help to prevent mitochondrial dysfunction and thereby to improve obesity
      related metabolic disorders such as diabetes and dyslipidemia of ZDF rats. 

PMID- 24867429
TI  - NanoLC/ESI+ HRMS3 quantitation of DNA adducts induced by 1,3-butadiene.
AB  - Human exposure to 1,3-butadiene (BD) present in automobile exhaust, cigarette
      smoke, and forest fires is of great concern because of its potent
      carcinogenicity. The adverse health effects of BD are mediated by its epoxide
      metabolites such as 3,4-epoxy-1-butene (EB), which covalently modify genomic DNA
      to form promutagenic nucleobase adducts. Because of their direct role in cancer,
      BD-DNA adducts can be used as mechanism-based biomarkers of BD exposure. In the
      present work, a mass spectrometry-based methodology was developed for accurate,
      sensitive, and precise quantification of EB-induced N-7-(1-hydroxy-3-buten-2-yl)
      guanine (EB-GII) DNA adducts in vivo. In our approach, EB-GII adducts are
      selectively released from DNA backbone by neutral thermal hydrolysis, followed by
      ultrafiltration, offline HPLC purification, and isotope dilution nanoLC/ESI(+)
      HRMS(3) analysis on an Orbitrap Velos mass spectrometer. Following method
      validation, EB-GII lesions were quantified in human fibrosarcoma (HT1080) cells
      treated with micromolar concentrations of EB and in liver tissues of rats exposed
      to sub-ppm concentrations of BD (0.5-1.5 ppm). EB-GII concentrations increased
      linearly from 1.15 +/- 0.23 to 10.11 +/- 0.45 adducts per 10(8) nucleotides in
      HT1080 cells treated with 0.5-10 MUM EB. EB-GII concentrations in DNA of
      laboratory rats exposed to 0.5, 1.0, and 1.5 ppm BD were 0.17 +/- 0.05, 0.33 +/-
      0.08, and 0.50 +/- 0.04 adducts per 10(8) nucleotides, respectively [corrected].
      We also used the new method to determine the in vivo half-life of EB-GII adducts
      in rat liver DNA (2.20 +/- 0.12 d) and to detect EB-GII in human blood DNA. To
      our knowledge, this is the first application of nanoLC/ESI(+)-HRMS(3) Orbitrap
      methodology to quantitative analysis of DNA adducts in vivo.

PMID- 24867434
TI  - Examining the antecedents of challenge and threat states: the influence of
      perceived required effort and support availability.
AB  - To date, limited research has explicitly examined the antecedents of challenge
      and threat states proposed by the biopsychosocial model. Thus, the aim of the
      present study was to examine the influence of perceived required effort and
      support availability on demand/resource evaluations, challenge and threat states,
      and motor performance. A 2 (required effort; high, low)*2 (support availability;
      available, not available) between-subjects design was used with one hundred and
      twenty participants randomly assigned to one of four experimental conditions.
      Participants received instructions designed to manipulate perceptions of required
      effort and support availability before demand/resource evaluations and
      cardiovascular responses were assessed. Participants then performed the novel
      motor task (laparoscopic surgery) while performance was recorded. Participants in
      the low perceived required effort condition evaluated the task as more of a
      challenge (i.e., resources outweighed demands), exhibited a cardiovascular
      response more indicative of a challenge state (i.e., higher cardiac output and
      lower total peripheral resistance), and performed the task better (i.e., quicker
      completion time) than those in the high perceived required effort condition.
      However, perceptions of support availability had no significant impact on
      participants' demand/resource evaluations, cardiovascular responses, or
      performance. Furthermore, there was no significant interaction effect between
      perceptions of required effort and support availability. The findings suggest
      that interventions aimed at promoting a challenge state should include
      instructions that help individuals perceive that the task is not difficult and
      requires little physical and mental effort to perform effectively. 

PMID- 24867436
TI  - Metal-free azaphosphaannulation of phosphonamides through intramolecular
      oxidative C-N bond formation.
AB  - We report an efficient metal-free azaphosphaannulation of a myriad of
      phosphonamides through intramolecular oxidative C-N bond formation using
      PhI(OAc)2 and iodine in acetonitrile under air, thus leading to the formation of
      benzazaphosphol-3-one 1-oxides, which are novel phosphorus heterocyclic
      privileged structures. 

PMID- 24867435
TI  - Bioethics in Denmark. Moving from first- to second-order analysis?
AB  - This article examines two current debates in Denmark--assisted suicide and the
      prioritization of health resources--and proposes that such controversial
      bioethical issues call for distinct philosophical analyses: first-order
      examinations, or an applied philosophy approach, and second-order examinations,
      what might be called a political philosophical approach. The authors argue that
      although first-order examination plays an important role in teasing out different
      moral points of view, in contemporary democratic societies, few, if any,
      bioethical questions can be resolved satisfactorily by means of first-order
      analyses alone, and that bioethics needs to engage more closely with second-order
      enquiries and the question of legitimacy in general.

PMID- 24867437
TI  - Molecular design of donor-acceptor dyes for efficient dye-sensitized solar cells
      I: a DFT study.
AB  - Dye-sensitized solar cells (DSSCs) have drawn great attention as low cost and
      high performance alternatives to conventional photovoltaic devices. The molecular
      design presented in this work is based on the use of pyran type dyes as donor
      based on frontier molecular orbitals (FMO) and theoretical UV-visible spectra in
      combination with squaraine type dyes as an acceptor. Density functional theory
      has been used to investigate several derivatives of pyran type dyes for a better
      dye design based on optimization of absorption, regeneration, and recombination
      processes in gas phase. The frontier molecular orbital (FMO) of the HOMO and LUMO
      energy levels plays an important role in the efficiency of DSSCs. These energies
      contribute to the generation of exciton, charge transfer, dissociation and
      exciton recombination. The computations of the geometries and electronic
      structures for the predicted dyes were performed using the B3LYP/6-31+G** level
      of theory. The FMO energies (EHOMO, ELUMO) of the studied dyes are calculated and
      analyzed in the terms of the UV-visible absorption spectra, which have been
      examined using time-dependent density functional theory (TD-DFT) techniques. This
      study examined absorption properties of pyran based on theoretical UV-visible
      absorption spectra, with comparisons between TD-DFT using B3LYP, PBE, and TPSSH
      functionals with 6-31+G (d) and 6-311++G** basis sets. The results provide a
      valuable guide for the design of donor-acceptor (D-A) dyes with high molar
      absorptivity and current conversion in DSSCs. The theoretical results indicated 4
      (dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran dye (D2-Me) can be
      effectively used as a donor dye for DSSCs. This dye has a low energy gap by
      itself and a high energy gap with squaraine acceptor type dye, the design that
      reduces the recombination and improves the photocurrent generation in solar cell.

PMID- 24867438
TI  - Reaction of chlorine radical with tetrahydrofuran: a theoretical investigation on
      mechanism and reactivity in gas phase.
AB  - Reaction of chlorine (Cl) radical with heterocyclic saturated ether,
      tetrahydrofuran has been studied. The detailed reactivity and mechanism of this
      reaction is analyzed using hybrid density functional theory (DFT), B3LYP and BB1K
      methods, and aug-cc-pVTZ basis set. To explore the mechanism of the reaction of
      tetrahydrofuran with Cl radical, four possible sites of hydrogen atom (H)
      abstraction pathways in tetrahydrofuran were analyzed. The barrier height and
      rate constants are calculated for the four H-abstraction channels. The BB1K
      calculated rate constant for alpha-axial H-abstraction is comparable with the
      experimentally determined rate constant. It reflects that alpha-axial H
      abstraction is the main degradation pathway of tetrahydrofuran with Cl radical.
      DFT-based reactivity descriptors are also calculated and these values describe
      alpha-axial H-abstraction as the main reaction channel. 

PMID- 24867440
TI  - APOE moderates the association between lifestyle activities and cognitive
      performance: evidence of genetic plasticity in aging.
AB  - The current study examined independent and interactive effects between
      Apolipoprotein E (APOE) genotype and two types of cognitively-stimulating
      lifestyle activities (CSLA)-integrated information processing (CSLA-II) and novel
      information processing (CSLA-NI)-on concurrent and longitudinal changes in
      cognition. Three-wave data across 6 years of follow-up from the Victoria
      Longitudinal Study (n=278; ages 55-94) and linear mixed model analyses were used
      to characterize the effects of APOE genotype and participation in CSLA-II and
      CSLA-NI in four cognitive domains. Significant CSLA effects on cognition were
      observed. More frequent participation in challenging activities (i.e., CSLA-NI)
      was associated with higher baseline scores on word recall, fact recall,
      vocabulary and verbal fluency. Conversely, higher participation in less
      cognitively-challenging activities (i.e., CSLA-II) was associated with lower
      scores on fact recall and verbal fluency. No longitudinal CSLA-cognition effects
      were found. Two significant genetic effects were observed. First, APOE moderated
      CSLA-II and CSLA-NI associations with baseline verbal fluency and fact recall
      scores. Second, APOE non-E4 carriers' baseline performance were more likely to be
      moderated by CSLA participation, compared to APOE-E4 carriers. Our findings
      suggest APOE may be a "plasticity" gene that makes individuals more or less
      amenable to the influence of protective factors such as CSLA.

PMID- 24867441
TI  - Assessing metacognition during a cognitive task: impact of "on-line"
      metacognitive questions on neuropsychological performances in a non-clinical
      sample.
AB  - Whereas metacognition is of great interest for neuropsychological practice,
      little is known about the impact of metacognitive questions during a
      neuropsychological assessment. This study explored the impact of measuring "on
      line" metacognitive processes on neuropsychological performances in a non
      clinical population. Participants were randomly assigned to a "standard" or a
      "metacognitive" neuropsychological test procedure. The "standard" procedure
      assessed executive functions (Modified Card Sorting Test), episodic memory
      ("Rappel libre Rappel indice" 16), working memory (digit span test Wechsler Adult
      Intelligence Scale III) and social cognition (Faces Test). In the "metacognitive"
      procedure, two questions were added after each item of these tests to evaluate
      "on-line" metacognitive monitoring and control. Working memory performances were
      better and episodic memory performances lower in the "metacognitive" versus the
      "standard" procedure. No significant difference was found concerning executive
      functioning or social cognition. The assessment of "on-line" metacognition might
      improve working memory performances by enhancing concentration, and might impair
      episodic memory performances by acting as a distractor. These findings may have
      implications for the development of cognitive remediation programs.

PMID- 24867442
TI  - Driving competences and neuropsychological factors associated to driving
      counseling in multiple sclerosis.
AB  - Multiple Sclerosis (MS) significantly impacts daily living activities, including
      car driving. To investigate driving difficulties experienced with MS, we compared
      50 MS patients with minor or moderate disability and 50 healthy controls (HC)
      using computerized driving tests (the ASDE driver test and the Useful Field of
      View (UFOV) test) and neuropsychological tests. Inclusion criteria included being
      active drivers. We evaluated whether cognitive deterioration in MS is associated
      with the results of driving tests by comparing MS patients without cognitive
      deterioration with HC. The results indicated that the MS patients performed worse
      than the HCs in attention, information processing, working memory and visuomotor
      coordination tasks. Furthermore, MS patients with cognitive impairments
      experienced more difficulties in the driving tests than did the non-impaired MS
      patients. Motor dysfunction associated with MS also played an important role in
      this activity. The results of this study suggest that MS should be assessed
      carefully and that special emphasis should be placed on visuomotor coordination
      and executive functions because patients with minor motor disability and subtle
      cognitive impairments can pass measures predictive of driving safety.

PMID- 24867445
TI  - Polar surface energies of iono-covalent materials: implications of a charge
      transfer model tested on Li2FeSiO4 surfaces.
AB  - The ionic compounds that are used as electrode materials in Li-based rechargeable
      batteries can exhibit polar surfaces that in general have high surface energies.
      We derive an analytical estimate for the surface energy of such polar surfaces
      assuming charge redistribution as a polarity compensating mechanism. The polar
      contribution to the converged surface energy is found to be proportional to the
      bandgap multiplied by the surface charge necessary to compensate for the
      depolarization field, and some higher order correction terms that depend on the
      specific surface. Other features, such as convergence behavior, coincide with
      published results. General conclusions are drawn on how to perform polar surface
      energy calculations in a slab configuration and upper boundaries of "purely"
      polar surface energies are estimated. Furthermore, we compare these findings with
      results obtained in a density functional theory study of Li(2)FeSiO(4) surfaces.
      We show that typical polar features are observed and provide a decomposition of
      surface energies into polar and local bond-cutting contributions for 29 different
      surfaces. We show that the model is able to explain subtle differences of GGA and
      GGA+U surface energy calculations.

PMID- 24867447
TI  - CORR Insights((r)): Carpal tunnel syndrome impairs thumb opposition and
      circumduction motion.

PMID- 24867446
TI  - Radial head reconstruction in elbow fracture-dislocation: monopolar or bipolar
      prosthesis?
AB  - BACKGROUND: Monopolar and bipolar radial head prosthetic arthroplasties have been
      used successfully to treat elbow fracture-dislocation with unsalvageable radial
      head fractures. The relative stability of these two designs in different clinical
      situations is a topic of ongoing investigation. QUESTIONS/PURPOSES: We tested the
      effects of monopolar and bipolar fixed-neck prosthetic radial head implants on
      improvement in elbow coronal and axial plane laxity in a terrible triad
      biomechanical model that accounted for lateral collateral ligament integrity and
      the presence of a transverse coronoid fracture. METHODS: Kinematic data were
      collected on six fresh-frozen cadaveric upper extremities tested with passive
      motion throughout the flexion arc. Varus and valgus gravity stress were applied
      with the wrist in neutral position. A lateral collateral ligament reconstruction
      was simulated. We assessed instability after radial head resection and
      reconstruction with either a monopolar or bipolar implant in the presence of a
      transversely fractured (Regan and Morrey Type 2) or fixed coronoid process.
      RESULTS: With collateral ligament integrity, no difference was detected, with the
      numbers available, in valgus laxity between implants under valgus stress (p =
      1.0). Laxity improvement with each prosthesis was higher when the coronoid was
      fractured (mean +/- SD: monopolar: 7.4 degrees  +/- 1.6 degrees , p < 0.001;
      bipolar: 6.4 degrees  +/- 1.6 degrees , p = 0.003) than when it was fixed
      (monopolar: 4.0 degrees  +/- 1.6 degrees , p = 0.02; bipolar: 4.2 degrees  +/-
      1.6 degrees , p = 0.01). With the numbers available, there was no difference in
      external rotation laxity between implants under valgus stress (p = 1.0). The
      greatest stabilizing effect of the prostheses occurred when the coronoid was
      fractured (monopolar: 3.3 degrees  +/- 1.2 degrees , p = 0.15; bipolar: 3.3
      degrees  +/- 1.2 degrees , p = 0.17). Radial head arthroplasty offered no
      substantial stability under varus stress for varus or internal rotation laxity.
      CONCLUSIONS: In our terrible triad cadaveric model, coronoid fixation was
      effective in improving varus laxity with a monopolar or bipolar prosthesis in
      place. Also, both types of prostheses were effective in improving valgus and
      external rotation laxity to the elbow, regardless of coronoid status. With
      collateral ligaments reconstructed, no large kinematic differences were noted
      between implants regardless of the varus-valgus position or whether the coronoid
      was fractured or fixed. CLINICAL RELEVANCE: The data from our cadaveric model
      support the use of either implant type in terrible triad injuries if the
      collateral ligaments are intact or reconstructed.

PMID- 24867448
TI  - Clinical faceoff: Anterior total hip versus mini-posterior: which one is better?

PMID- 24867449
TI  - Is potential malnutrition associated with septic failure and acute infection
      after revision total joint arthroplasty?
AB  - BACKGROUND: Although malnutrition has been hypothesized to increase the risk of
      periprosthetic joint infection (PJI), strong evidence linking the two is lacking.
      QUESTIONS/PURPOSES: The purposes of this study were to determine (1) if one or
      more laboratory values suggestive of malnutrition is independently associated
      with being revised for an infected joint arthroplasty as opposed to for an
      aseptic failure; (2) the relationship between laboratory parameters suggestive of
      malnutrition and obesity; and (3) if one or more laboratory parameters suggestive
      of malnutrition is independently associated with acute PJI complicating an
      aseptic revision procedure. METHODS: Between 2002 and 2010, one surgeon performed
      600 revision total joint arthroplasties in 547 patients; during that time,
      nutritional parameters (including serum albumin, total lymphocyte count, and
      transferrin) were routinely obtained preoperatively; complete data sets were
      available on 454 patients (501 procedures [84%]). We compared the frequency of
      having one or more laboratory parameters suggestive of malnutrition between
      patients undergoing a revision for septic reasons and aseptic reasons as well as
      between obese and nonobese patients. The 375 aseptic revisions were then assessed
      for the incidence of acute postoperative infection (within 90 days, diagnosed
      with Musculoskeletal Infection Society criteria). Multivariate logistic
      regression modeling was used to evaluate factors independently associated with
      (1) a septic as opposed to an aseptic mode of failure; and (2) acute
      postoperative infection after an aseptic revision. RESULTS: Patients in 67 of 126
      (53%) revisions for PJI had one or more laboratory parameters suggestive of
      malnutrition compared with 123 of 375 (33%) undergoing revision for a
      noninfectious etiology (odds ratio [OR], 2.3 [95% confidence interval, 1.5-3.5];
      p<0.001). Patients who were of normal weight at the time of revision had the
      highest frequency of laboratory parameters suggestive of malnutrition (42 of 82
      [51%]), although this was common in obese patients as well (76 of 238 [32%])
      (p=0.002). Among the 375 aseptic revisions, 12 developed an acute postoperative
      infection (3%). The frequency of infection was nine of 123 in the group having
      one or more laboratory parameters suggestive of malnutrition and three of 252 in
      the group not having such laboratory parameters (7% versus 1%; p=0.003).
      Multivariate regression revealed that having laboratory parameters suggestive of
      malnutrition is independently associated with both chronic PJI (p=0.003; OR, 2.1)
      and an acute postoperative infection complicating an aseptic revision
      arthroplasty (p=0.02; OR, 5.9). CONCLUSIONS: Having one or more laboratory
      parameters suggestive of malnutrition is common among patients undergoing
      revision arthroplasty and is independently associated with both chronic septic
      failure and acute postoperative infection complicating a revision performed for a
      noninfectious etiology. Future studies should assess the impact of a standardized
      screening protocol with subsequent correction of abnormal laboratory parameters
      suggestive of malnutrition on the risk of PJI to determine a potential causal
      relationship between the two. LEVEL OF EVIDENCE: Level III, prognostic study. See
      Guidelines for Authors for a complete description of levels of evidence.

PMID- 24867450
TI  - The Elixhauser comorbidity method outperforms the Charlson index in predicting
      inpatient death after orthopaedic surgery.
AB  - BACKGROUND: Scores derived from comorbidities can help with risk adjustment of
      quality and safety data. The Charlson and Elixhauser comorbidity measures are
      well-known risk adjustment models, yet the optimal score for orthopaedic patients
      remains unclear. QUESTIONS/PURPOSES: We determined whether there was a difference
      in the accuracy of the Charlson and Elixhauser comorbidity-based measures in
      predicting (1) in-hospital mortality after major orthopaedic surgery, (2) in
      hospital adverse events, and (3) nonroutine discharge. METHODS: Among an
      estimated 14,007,813 patients undergoing orthopaedic surgery identified in the
      National Hospital Discharge Survey (1990-2007), 0.80% died in the hospital. The
      association of each Charlson comorbidity measure and Elixhauser comorbidity
      measure with mortality was assessed in bivariate analysis. Two main multivariable
      logistic regression models were constructed, with in-hospital mortality as the
      dependent variable and one of the two comorbidity-based measures (and age, sex,
      and year of surgery) as independent variables. A base model that included only
      age, sex, and year of surgery also was evaluated. The discriminative ability of
      the models was quantified using the area under the receiver operating
      characteristic curve (AUC). The AUC quantifies the ability of our models to
      assign a high probability of mortality to patients who die. Values range from
      0.50 to 1.0, with 0.50 indicating no ability to discriminate and 1.0 indicating
      perfect discrimination. RESULTS: Elixhauser comorbidity adjustment provided a
      better prediction of in-hospital case mortality (AUC, 0.86; 95% CI, 0.86-0.86)
      compared with the Charlson model (AUC, 0.83; 95% CI, 0.83-0.84) and to the base
      model with no comorbidities (AUC, 0.81; 95% CI, 0.81-0.81). In terms of relative
      improvement in predictive performance, the Elixhauser measure performed 60%
      better than the Charlson score in predicting mortality. The Elixhauser model
      discriminated inpatient morbidity better than the Charlson measure, but the
      discriminative ability of the model was poor and the difference in the absolute
      improvement in predictive power between the two models (AUC, 0.01) is of dubious
      clinical importance. Both comorbidity models exhibited the same degree of
      discrimination for estimating nonroutine discharge (AUC, 0.81; 95% CI, 0.81-0.82
      for both models). CONCLUSIONS: Provider-specific outcomes, particularly inpatient
      mortality, may be evaluated differently depending on the comorbidity risk
      adjustment model selected. Future research assessing and comparing the
      performance of the Charlson and Elixhauser measures in predicting long-term
      outcomes would be of value. LEVEL OF EVIDENCE: Level II, prognostic study. See
      the Instructions for Authors for a complete description of levels of evidence.

PMID- 24867451
TI  - Does imageless computer-assisted TKA lead to improved rotational alignment or
      fewer outliers? A systematic review.
AB  - BACKGROUND: Computer-assisted surgery (CAS) has been developed to enhance
      prosthetic alignment during primary TKAs. Imageless CAS improves coronal and
      sagittal alignment compared with conventional TKA. However, the effect of
      imageless CAS on rotational alignment remains unclear. QUESTIONS/PURPOSES: We
      conducted a systematic and qualitative review of the current literature regarding
      the effectiveness of imageless CAS during TKA on (1) rotational alignment of the
      femoral and tibial components and tibiofemoral mismatch in terms of deviation
      from neutral rotation, and (2) the number of femoral and tibial rotational
      outliers. METHODS: Data sources included PubMed, MEDLINE, and EMBASE. Study
      selection, data extraction, and methodologic quality assessment were conducted
      independently by two reviewers. Standardized mean difference with 95% CI was
      calculated for continuous variables (rotational alignment of the femoral or
      tibial component and tibiofemoral mismatch). To compare the number of outliers
      for femoral and tibial component rotation, the odds ratio and 95% CI were
      calculated. The literature search produced 657 potentially relevant studies, 17
      of which met the inclusion criteria. One study was considered as having high
      methodologic quality, 15 studies had medium, and one study had low quality.
      RESULTS: Conflicting evidence was found for all outcome measures except for
      tibiofemoral mismatch. Moderate evidence was found that imageless CAS had no
      influence on postoperative tibiofemoral mismatch. The measurement protocol for
      measuring tibial rotation varied among the studies and in only one of the studies
      was the sample size calculation based on one of the outcome measures used in our
      systematic review. CONCLUSIONS: More studies of high methodologic quality and
      with a sample size calculation based on the outcome measures will be helpful to
      assess whether an imageless CAS TKA improves femoral and tibial rotational
      alignment and tibiofemoral mismatch or decreases the number of femoral and tibial
      rotational outliers. To statistically analyze the results of different studies,
      the same measurement protocol should be used among the studies.

PMID- 24867452
TI  - Classifications in brief: young and burgess classification of pelvic ring
      injuries.

PMID- 24867453
TI  - CT-generated radiographs in obese patients with acetabular fractures: can they be
      used in lieu of plain radiographs?
AB  - BACKGROUND: Acetabular fracture diagnosis is traditionally made with AP and
      oblique pelvic plain radiographs. Obesity may impair diagnostic accuracy of plain
      radiographs. New CT reconstruction algorithms allow for simulated radiographs
      that may eliminate the adverse imaging effects of obesity. QUESTIONS/PURPOSES: In
      obese patients with acetabular fractures, we compared CT-generated and plain
      radiographs in terms of (1) ability to classify fracture type, (2) agreement in
      fracture classification, and (3) surgeon performance at different experience
      levels. METHODS: CT-generated and plain radiograph image sets were created for 16
      obese (BMI>35) patients with 17 acetabular fractures presenting from 2009 to
      2011. Three orthopaedic trauma attending physicians, three senior residents, and
      three junior residents independently viewed these sets and recorded their
      diagnoses. These diagnoses were compared to the postoperative findings, which we
      defined as the gold standard for diagnosis. To assess intraobserver reliability,
      the same observers reviewed a rerandomized set 1 month later. We had 80% power to
      detect a 25% difference in the percentage of correctly classified fractures based
      on a post hoc sample size calculation and 80% power to detect a 0.10 difference
      in kappa value based on both a priori and post hoc sample size calculations.
      RESULTS: With the numbers available (153 observations in each image set, 51 for
      each of the three observer groups), we found no differences between CT-generated
      and plain radiographs, respectively, in terms of percentage of correct diagnoses
      for the observer groups (all observers: 54% versus 49%, p=0.48; attendings: 61%
      versus 59%, p=0.83; senior residents: 51% versus 53%, p=0.84; and junior
      residents: 49% versus 35%, p=0.16). Furthermore, agreement between CT-generated
      and plain radiographic fracture classifications was substantial (kappa=0.67).
      Nonetheless, the attending and senior resident groups performed better in
      correctly classifying the fracture than the junior residents when using plain
      radiographs (p=0.01 and p=0.049, respectively). Performance was not different
      when comparing the attendings to the senior resident and junior groups or
      comparing the senior residents to the junior residents using CT-generated
      radiographs (p=0.32, p=0.22, and p=0.83, respectively). CONCLUSIONS: CT-generated
      radiographs are as good as plain radiographs for experienced surgeons for
      classifying acetabular fractures in obese patients. CT-generated imaging may be
      valuable in both teaching and clinical settings, and it may spare the patient
      additional radiation exposure and discomfort. LEVEL OF EVIDENCE: Level II,
      diagnostic study. See the Instructions for Authors for a complete description of
      levels of evidence.

PMID- 24867454
TI  - Does competing risk analysis give useful information about endoprosthetic
      survival in extremity osteosarcoma?
AB  - BACKGROUND: Conventional survival analysis for endoprosthetic complications does
      not consider competing events adequately. Patients who die of their disease are
      no longer at risk for complications; therefore, death as a competing event may
      alter survivorship estimates in the orthopaedic-oncological setting.
      QUESTIONS/PURPOSES: This investigation aimed to compare (1) endoprosthetic
      survivorship after osteosarcoma by Kaplan-Meier analysis; and (2) by a competing
      risk model. METHODS: Between 1981 and 2009, we performed 247 modular
      endoprostheses for patients with extremity osteosarcoma; 73 patients had a
      followup of less than 2 years but all patients were included in statistical
      analysis. No patients were lost to followup for reasons other than death.
      Revision-free endoprosthetic survival until soft tissue failure (Type 1), aseptic
      loosening (Type 2), structural failure (Type 3), infection (Type 4), and local
      tumor progression (Type 5) was estimated according to a Kaplan-Meier analysis and
      a competing risk model. Sixty-four patients died throughout followup; the 5- and
      10-year overall survival and metastasis-free survival were 72% and 70% and 70%
      and 69%, respectively. One hundred twenty-two patients (49%) had complications.
      RESULTS: Competing risk analysis consistently resulted in reduced estimates of
      the frequency of complications and reconstructive failures compared with Kaplan
      Meier analysis. Cumulative risks for complication Types 1 to 5 at 10 years
      without/with death as a competing event revealed a risk of 19%/16% for Type 1,
      26%/20% for Type 2, 51%/38% for Type 3, 23%/20% for Type 4, and 4%/3% for Type 5.
      CONCLUSIONS: A competing risk model reveals considerably reduced risks for every
      complication compared with Kaplan-Meier analysis when death is included as a
      competing event. Because it more realistically represents the risks of
      complications, competing risk models should be used to arrive at risk estimates
      for purposes of counseling patients about those risks associated with modular
      endoprosthetic reconstruction. LEVEL OF EVIDENCE: Level III, therapeutic study.
      See Guidelines for Authors for a complete description of levels of evidence.

PMID- 24867455
TI  - Aggressive tibial lesion in a 70-year-old man.

PMID- 24867456
TI  - A novel organic-inorganic hybrid constructed from the Nyman-type dititanoniobate
      [Ti2Nb8O28](8-) and copper-organic cations.
AB  - A new organic-inorganic hybrid titaniobate compound,
      [Cu(en)2][Cu(en)2(H2O)2]3[Ti2Nb8O28].8H2O (1) (en = ethylenediamine), was
      successfully synthesized, characterized by single-crystal X-ray diffraction, IR
      spectroscopy, thermogravimetric analysis (TGA) and UV-Vis diffuse reflectance
      spectroscopy and its photoluminescence studied. 

PMID- 24867457
TI  - Carbocatalysis by graphene-based materials.

PMID- 24867458
TI  - Do cancer patients tweet? Examining the twitter use of cancer patients in Japan.
AB  - BACKGROUND: Twitter is an interactive, real-time media that could prove useful in
      health care. Tweets from cancer patients could offer insight into the needs of
      cancer patients. OBJECTIVE: The objective of this study was to understand cancer
      patients' social media usage and gain insight into patient needs. METHODS: A
      search was conducted of every publicly available user profile on Twitter in Japan
      for references to the following: breast cancer, leukemia, colon cancer, rectal
      cancer, colorectal cancer, uterine cancer, cervical cancer, stomach cancer, lung
      cancer, and ovarian cancer. We then used an application programming interface and
      a data mining method to conduct a detailed analysis of the tweets from cancer
      patients. RESULTS: Twitter user profiles included references to breast cancer
      (n=313), leukemia (n=158), uterine or cervical cancer (n=134), lung cancer
      (n=87), colon cancer (n=64), and stomach cancer (n=44). A co-occurrence network
      is seen for all of these cancers, and each cancer has a unique network
      conformation. Keywords included words about diagnosis, symptoms, and treatments
      for almost all cancers. Words related to social activities were extracted for
      breast cancer. Words related to vaccination and support from public insurance
      were extracted for uterine or cervical cancer. CONCLUSIONS: This study
      demonstrates that cancer patients share information about their underlying
      disease, including diagnosis, symptoms, and treatments, via Twitter. This
      information could prove useful to health care providers.

PMID- 24867459
TI  - Quality of Life in Patients with Noninfectious Uveitis Treated with or without
      Systemic Anti-inflammatory Therapy.
AB  - PURPOSE: To compare vision-related (VR-QOL) and health-related quality of life
      (HR-QOL) in patients with noninfectious uveitis treated with systemic anti
      inflammatory therapy versus nonsystemic therapy. METHODS: A prospective, cross
      sectional study design was employed. VR-QOL and HR-QOL were assessed by the 25
      Item Visual Function Questionnaire (VFQ-25) and the Short Form 12-Item Health
      Survey (SF-12), respectively. Multivariate regression analysis was performed to
      assess the VR-QOL and HR-QOL based on treatment. RESULTS: Among the 80 patients,
      the median age was 51 years with 28 males (35%). The adjusted effect of treatment
      modality on VR-QOL or HR-QOL showed no statistically significant difference in
      all subscores of VFQ-25 or physical component score (PCS) and mental component
      score (MCS) of SF-12. Systemic therapy did not compromise VR-QOL or HR-QOL
      compared to nonsystemic therapy. CONCLUSIONS: Systemic therapy can be effectively
      used to control serious cases of noninfectious uveitis without significant
      relative adverse impact on quality of life.

PMID- 24867461
TI  - Is light transmittance aggregometry still a useful tool to assess pharmacodynamic
      effects of antiplatelet therapy?

PMID- 24867460
TI  - Modeling the effects of beta1-adrenergic receptor blockers and polymorphisms on
      cardiac myocyte Ca2+ handling.
AB  - beta-Adrenergic receptor blockers (beta-blockers) are commonly used to treat
      heart failure, but the biologic mechanisms governing their efficacy are still
      poorly understood. The complexity of beta-adrenergic signaling coupled with the
      influence of receptor polymorphisms makes it difficult to intuit the effect of
      beta-blockers on cardiac physiology. While some studies indicate that beta
      blockers are efficacious by inhibiting beta-adrenergic signaling, other studies
      suggest that they work by maintaining beta-adrenergic responsiveness. Here, we
      use a systems pharmacology approach to test the hypothesis that in ventricular
      myocytes, these two apparently conflicting mechanisms for beta-blocker efficacy
      can occur concurrently. We extended a computational model of the beta(1)
      adrenergic pathway and excitation-contraction coupling to include detailed
      receptor interactions for 19 ligands. Model predictions, validated with Ca(2+)
      and Forster resonance energy transfer imaging of adult rat ventricular myocytes,
      surprisingly suggest that beta-blockers can both inhibit and maintain signaling
      depending on the magnitude of receptor stimulation. The balance of inhibition and
      maintenance of beta(1)-adrenergic signaling is predicted to depend on the
      specific beta-blocker (with greater responsiveness for metoprolol than
      carvedilol) and beta(1)-adrenergic receptor Arg389Gly polymorphisms.

PMID- 24867462
TI  - Phylogenetic relationships among Synallaxini spinetails (Aves: Furnariidae)
      reveal a new biogeographic pattern across the Amazon and Parana river basins.
AB  - Relationships among genera in the tribe Synallaxini have proved difficult to
      resolve. In this study, I investigate relationships among Synallaxis, Certhiaxis
      and Schoeniophylax using DNA sequences from the mitochondrion and three nuclear
      regions. I implemented novel primers and protocols for amplifying and sequencing
      autosomal and sex-linked introns in Furnariidae that resolved basal relationships
      in the Synallaxini with strong support. Synallaxis propinqua is sister to
      Schoeniophylax phryganophilus, and together they form a clade with Certhiaxis.
      The results are robust to analytical approaches when all genomic regions are
      analyzed jointly (parsimony, maximum likelihood, and species-tree analysis) and
      the same basal relationships are recovered by most genomic regions when analyzed
      separately. A sister relationship between S. propinqua, an Amazonian river island
      specialist, and S. phryganophilus, from the Parana River basin region, reveals a
      new biogeographic pattern shared by at least other four pairs of taxa with
      similar distributions and ecologies. Estimates of divergence times for these five
      pairs span from the late Miocene to the Pleistocene. Identification of the
      historical events that produced this pattern is difficult and further advances
      will require additional studies of the taxa involved and a better understanding
      of the recent environmental history of South America. A new classification is
      proposed for the Synallaxini, including the description of a new genus for S.
      propinqua. 

PMID- 24867464
TI  - Modulation of uPA, MMPs and their inhibitors by a novel nutrient mixture in human
      glioblastoma cell lines.
AB  - Brain tumors are highly aggressive tumors that are characterized by high levels
      of matrix metalloproteinase (MMP)-2 and -9 secretions that degrade the
      extracellular matrix (ECM) and basement membrane, allowing cancer cells to spread
      to distal organs. Proteases play a key role in tumor cell invasion and metastasis
      by digesting the basement membrane and ECM components. Strong clinical and
      experimental evidence demonstrates association of elevated levels of urokinase
      plasminogen activators (uPA) and MMPs with cancer progression, metastasis and
      shortened patient survival. MMP activities are regulated by specific tissue
      inhibitors of metalloproteinases (TIMPs). Our main objective was to study the
      effect of a nutrient mixture (NM) on the activity of uPA, MMPs and TIMPs in
      various human gliomas. Human glioblastoma (LN-18, T-98G and A-172) cell lines
      (ATCC) were cultured in their respective media and treated at confluence with NM
      at 0, 50, 100, 250, 500 and 1000 ug/ml. Analysis of uPA activity was carried out
      by fibrin zymography, MMPs by gelatinase zymography and TIMPs by reverse
      zymography. Glioblastoma cell lines LN-18 and T-98G expressed uPA, which was
      inhibited by NM in a dose-dependent manner. However, no bands corresponding to
      uPA were detected for the A-172 cell line. On gelatinase zymography, all three
      cell lines showed bands corresponding to MMP-2 and LN-18 and T-98G showed PMA
      (100 ng/ml)-induced MMP-9. NM inhibited their expression in a dose-dependent
      manner. Activity of TIMP-2 was upregulated by NM in all glioma cell lines in a
      dose-dependent manner. Analysis revealed a positive correlation between uPA and
      MMP-2 and a negative correlation between uPA/MMPs and TIMP-2. These findings
      suggest the therapeutic potential of NM in the treatment of gliomas.

PMID- 24867465
TI  - Defining the outcome of patients with delayed diagnosis of differentiated thyroid
      cancer.
AB  - OBJECTIVES/HYPOTHESIS: In the present study we sought to define the outcome of
      patients with delay in diagnosis and treatment (>1 year) of well-differentiated
      thyroid carcinoma (WDTC) due to initial benign cytology (IBC). STUDY DESIGN:
      Retrospective medical record review and analysis of survival outcomes. METHODS:
      The records of 47 patients with delayed diagnosis of thyroid cancer were
      reviewed. In 38, surgery was performed for growing nodules and in nine due to
      malignant cytology during follow-up. Median time to delayed surgery was 52 months
      (range, 13-205 months). Multivariate analysis was performed to assess variables
      associated with outcome. RESULTS: Most patients (32/47) underwent total
      thyroidectomy, whereas 15/47 had hemithyroidectomy. With a median follow-up of 96
      months (range, 12-184 months), the 5-year disease-free survival of these patients
      was 96%. Multivariate analysis showed that the outcome of these patients was not
      statistically different than that of patients (n = 162) who underwent immediate
      surgery for similar disease. CONCLUSIONS: We show that patients with delayed
      diagnosis and treatment for WDTC due to IBC have excellent outcome. LEVEL OF
      EVIDENCE: 4.

PMID- 24867466
TI  - Injury, disability and access to care in Rwanda: results of a nationwide cross
      sectional population study.
AB  - BACKGROUND: Disparities in access to quality injury care are a growing concern
      worldwide, with over 90 % of global injury-related morbidity and mortality
      occurring in low-income countries. We describe the use of a survey tool that
      evaluates the prevalence of surgical conditions at the population level, with a
      focus on the burden of traumatic injuries, subsequent disabilities, and barriers
      to injury care in Rwanda. METHODS: The Surgeons OverSeas Assessment of Surgical
      Need (SOSAS) tool is a cross-sectional, cluster-based population survey designed
      to measure conditions that may necessitate surgical consultation or intervention.
      Questions are structured anatomically and designed around a representative
      spectrum of surgical conditions. Households in Rwanda were sampled using two
      stage cluster sampling, and interviews were conducted over a one-month period in
      52 villages nationwide, with representation of all 30 administrative districts.
      Injury-related results were descriptively analyzed and population-weighted by age
      and gender. RESULTS: A total of 1,627 households (3,175 individuals) were
      sampled; 1,185 lifetime injury-related surgical conditions were reported, with 38
      % resulting in some form of perceived disability. Of the population, 27.4 % had
      ever had a serious injury-related condition, with 2.8 % having an injury-related
      condition at the time of interview. Over 30 % of household deaths in the previous
      year may have been surgically treatable, but only 4 % were injury-related.
      CONCLUSIONS: Determining accurate injury and disability burden is crucial to
      health system planning in low-income countries. SOSAS is a useful survey for
      determining injury epidemiology at the community level, which can in turn help to
      plan prevention efforts and optimize provision of care.

PMID- 24867467
TI  - Postoperative complications do not affect long-term outcome in esophageal cancer
      patients.
AB  - BACKGROUND: As esophagectomy is associated with a considerable complication rate,
      the aim of this study was to assess the impact of postoperative complications and
      neoadjuvant treatment on long-term outcome of adenocarcinoma (EAC) and squamous
      cell carcinoma (SCC) patients. METHODS: Altogether, 134 patients undergoing
      transthoracic esophagectomy between 2005 and 2010 with intrathoracic stapler
      anastomosis were included in the study. Postoperative complications were
      allocated into three main categories: overall complications, acute anastomotic
      insufficiency, and pulmonary complications. Data were collected prospectively and
      reviewed retrospectively for the purpose of this study. RESULTS: SCC patients
      suffered significantly more often from overall and pulmonary complications (SCC
      vs. EAC: overall complications 67 vs. 45 %, p = 0.044; pulmonary complications 56
      vs. 34 %, p = 0.049). The anastomotic insufficiency rates did not differ
      significantly (SCC 11%, EAC 15%, p = 0.69). Long-term survival of EAC and SCC
      patients was not affected by perioperative (overall/pulmonary) complications or
      by the occurrence of anastomotic insufficiency. Also, neoadjuvant treatment did
      not influence the incidence of complications or long-term survival. CONCLUSIONS:
      This is the first time the patient population of a center experienced with
      esophageal cancer surgery was assessed for the occurrence of general and
      esophageal cancer surgery-specific perioperative complications. Our results
      indicated that these complications did not affect long-term survival of EAC and
      SCC patients. Our data support the hypothesis that neoadjuvant treatment might
      not affect the incidence of perioperative complications or long-term survival
      after treatment of these tumor subtypes.

PMID- 24867468
TI  - Postoperative vocal cord dysfunction despite normal intraoperative
      neuromonitoring: an unexpected complication with the risk of bilateral palsy.
AB  - BACKGROUND: Intraoperative neuromonitoring (IONM) has become standard practice in
      thyroid surgery for many surgeons. It reduces the risk of vocal cord palsy in
      high-risk patients and has led to two-stage operations to prevent bilateral
      palsies. The specificity of detecting nerve injuries is not 100 %, leading to
      patients with vocal cord dysfunction (VCD) despite regular neuromonitoring (false
      negative IONM). We aimed to evaluate possible risk factors for this phenomenon
      and its importance regarding bilateral palsies. METHODS: We performed a
      retrospective analysis of all patients with false-negative IONM. RESULTS: A total
      of 2152 patients (3426 nerves at risk) underwent surgery for benign disease
      between January 2008 and October 2010. Sensitivity for predicting VCD was 85.4 %
      and specificity 99.0 %. The positive predictive value was 68.0 % and the negative
      predictive value 99.6 %. We were not able to identify risk factors for false
      negative IONM. We found four patients with delayed occurrence of VCD after
      regular IONM (1-8 weeks). We registered two patients with bilateral VCD after
      false negative IONM on the first side of bilateral resections (2/7) and four
      patients with bilateral palsy after correct IONM (4/1256). The relative risk for
      bilateral VCD between patients with false-negative IONM on the primary resection
      side and patients with correct IONM was 89.7. CONCLUSIONS: Although seldom, false
      negative IONM is of clinical importance as it bears a high risk of bilateral VCD
      if it occurs on the first side of a bilateral resection. It can also have a
      latent occurrence after surgery.

PMID- 24867469
TI  - Single-port and multi-port laparoscopic left lateral liver sectionectomy for
      treating benign liver diseases: a prospective, randomized, controlled study.
AB  - BACKGROUND: The use of single-port laparoscopy for left-lateral liver
      sectionectomy (LLLS) has been reported in the literature, but the effectiveness
      and safety of LLLS has not been validated in randomized, controlled trials. This
      prospective randomized controlled trial compared the effectiveness and safety of
      single-port and multi-port laparoscopic LLLS for the surgical treatment of benign
      liver disease. METHODS: Altogether, 38 patients aged 17-65 years (16 men, 22
      women) with benign liver diseases were hospitalized for elective laparoscopic
      LLLS between January 2010 and December 2012. Patients were randomly assigned to
      either single-port (n = 19) or multi-port (n = 19) laparoscopic LLLS. Main
      outcome measures were operative time, volume of intraoperative blood loss,
      complication rates, and postoperative hospitalization. RESULTS: Baseline
      characteristics of the two groups were comparable. Single-port and multi-port
      laparoscopies were successfully completed in all but one patient (1/19, 5.3 %)
      who required conversion from a single-port to a multi-port procedure. The two
      groups had similar mean operative times and volumes of intraoperative blood loss.
      There were no clinically significant postoperative complications or deaths. The
      single-port group had a significantly shorter postoperative hospitalization than
      the multi-port group (2.5 +/- 1.7 vs. 4.0 +/- 2.1 days; p < 0.05). CONCLUSIONS:
      Single-port laparoscopic LLLS is a technically feasible, effective, safe
      alternative to multi-port laparoscopy for the treatment of benign liver diseases
      in cautiously selected patients.

PMID- 24867470
TI  - Study of serum leptin in well-differentiated thyroid carcinoma: correlation with
      patient and tumor characteristics.
AB  - BACKGROUND: There is a proven relationship between obesity and several cancers
      including breast, endometrium, colorectal, and esophagus. With the increasing
      incidence of both obesity and thyroid cancer, we designed the present study to
      investigate a causal relationship between leptin, which is one of the well known
      adipokines, and well-differentiated thyroid cancer (WDTC). METHODS: Serum leptin
      levels were measured in 30 patients with WDTC and compared to 30 healthy control
      subjects before and 1 month after surgery. Other parameters studied included age,
      sex, body mass index, menopausal status in women, lymph node status, tumor size,
      and disease multifocality. RESULTS: There were no differences between the two
      groups regarding age and sex. Preoperative leptin levels were higher in the WDTC
      patients when compared to the control patients [19.25 (1.50-109.60) vs 0.90 (0.50
      11.80) ng/ml, p < 0.001, group 1 vs group 2, respectively]. A significant drop in
      leptin levels 1 month after surgery occurred in the WDTC group, falling from
      19.25 (1.50-109.60) to 0.90 (0.60-8.90) ng/ml (p < 0.001). This did not occur in
      the control group (p = 0.274). Lymph node involvement, tumor size, and
      multifocality had no effect on leptin levels, although trends were observed (p =
      0.48, 0.079, and 0.064), respectively. CONCLUSIONS: Serum leptin levels were
      significantly higher in WDTC patients when compared to control group patients,
      with a significant drop after surgery. Leptin may play a role in diagnosis of
      WDTC; however, its prognostic value is still undetermined.

PMID- 24867471
TI  - A novel method for laparoscopic splenectomy in the setting of hypersplenism
      secondary to liver cirrhosis: ten years' experience.
AB  - BACKGROUND: It is a technical challenge to perform laparoscopic splenectomy (LS)
      on patients with liver cirrhosis. The purpose of this article is to share our
      experience with performing LS in the setting of hypersplenism secondary to liver
      cirrhosis. METHODS: A total of 43 LSs for hypersplenism secondary to liver
      cirrhosis were performed between September 2003 and January 2013. The patients
      studied in this series were consecutively enrolled. All of the surgeries were
      performed by a single surgeon. We divided our patients into two groups based on
      whether splenogastric ligament-entranced laparoscopic splenectomy (SLELS) was
      used. Data were collected retrospectively by chart review. RESULTS: The patients
      in the two groups had comparable demographic characteristics. Patients who
      underwent LS with SLELS (group 2) required less operating time (195.2 +/- 45.8
      vs. 227.7 +/- 52.1 min, p = 0.042) and suffered less blood loss (160.4 +/- 107.6
      vs. 270.1 +/- 231.2 ml, p = 0.031). No significant difference was found in terms
      of blood transfusion, conversion, postoperative hospital stay, and complications.
      CONCLUSIONS: It is safe and feasible to perform LS on patients with hypersplenism
      secondary to liver cirrhosis. In the procedure of SLELS, we highlight the
      importance of sufficient elevation the upper pole of the spleen.

PMID- 24867472
TI  - Two anatomical pathways for retroperitoneoscopic pancreatectomy: indications for
      the posterior and lateral approaches.
AB  - BACKGROUND: Retroperitoneoscopic pancreatectomy (RP) is a novel surgical
      procedure that is safe and feasible in animal models and clinical practice.
      However, the optimal approach for RP has not been established. OBJECTIVE: This
      study aimed to introduce the posterior and lateral approaches for RP. METHODS:
      This prospective study included 19 patients with suspected pancreatic lesions who
      underwent RP. RP was performed using either a posterior or a lateral approach.
      RESULTS: The posterior, lateral, and jointed approaches were used in 13 (68.4 %),
      3 (15.8 %), and 3 (15.8 %) cases, respectively. Patients underwent enucleation (N
      = 8), distal pancreatectomy (N = 4), and resection of cystic pancreatic lesions
      (N = 2) and non-pancreatic lesions (N = 5). All retroperitoneoscopic procedures
      were successfully accomplished with no conversion to open or laparoscopic
      surgery. Intraoperative complications occurred in two (12.5 %) cases, including
      one case with injury to the peritoneum and one case with injury to the peritoneum
      and splenic vein. Postoperative grade A pancreatic fistulas occurred in six
      cases, and were cured by delayed drainage. No disease recurrence or abnormal
      symptoms were observed during the mean follow-up period of 14.06 +/- 9.60 months.
      CONCLUSIONS: RP using the posterior or lateral approach is feasible and
      effective, but has different indications. The posterior approach is useful for
      distal pancreatectomy, as well as resection of pancreatic lesions in the
      posterior or superoposterior region of the distal pancreas. The lateral approach
      is useful for resection of pancreatic lesions in the anterior or inferior region
      of the body and tail. The two approaches can be used in combination or
      conversion.

PMID- 24867473
TI  - The impact of resident- and self-evaluations on surgeon's subsequent teaching
      performance.
AB  - BACKGROUND: This study evaluates how residents' evaluations and self-evaluations
      of surgeon's teaching performance evolve after two cycles of evaluation,
      reporting, and feedback. Furthermore, the influence of over- and underestimating
      own performance on subsequent teaching performance was investigated. METHODS: In
      a multicenter cohort study, 351 surgeons evaluated themselves and were also
      evaluated by residents during annual evaluation periods for three subsequent
      years. At the end of each evaluation period, surgeons received a personal report
      summarizing the residents' feedback. Changes in each surgeon's teaching
      performance evaluated on a five-point scale were studied using growth models. The
      effect of surgeons over- or underestimating their own performance on the
      improvement of teaching performance was studied using adjusted multivariable
      regressions. RESULTS: Compared with the first (median score: 3.83, 20th to 80th
      percentile score: 3.46-4.16) and second (median: 3.82, 20th to 80th: 3.46-4.14)
      evaluation period, residents evaluated surgeon's teaching performance higher
      during the third evaluation period (median: 3.91, 20th to 80th: 3.59-4.27), p <
      0.001. Surgeons did not alter self-evaluation scores over the three periods.
      Surgeons who overestimated their teaching performance received lower subsequent
      performance scores by residents (regression coefficient b: -0.08, 95 % confidence
      limits (CL): -0.18, 0.02) and self (b: -0.12, 95 % CL: -0.21, -0.02). Surgeons
      who underestimated their performance subsequently scored themselves higher (b:
      0.10, 95 % CL: 0.03, 0.16), but were evaluated equally by residents. CONCLUSIONS:
      Residents' evaluation of surgeon's teaching performance was enhanced after two
      cycles of evaluation, reporting, and feedback. Overestimating own teaching
      performance could impede subsequent performance.

PMID- 24867476
TI  - Excimer-monomer switch: a reaction-based approach for selective detection of
      fluoride.
AB  - A N-aryl-1,8-naphthalimide based sensor (ES-1) bearing a trimethylsilyl ether has
      been synthesized by a two-step reaction for quantitative detection of fluoride
      (F(-)). ES-1 exhibited monomer/excimer emissions at 410 and 524 nm respectively
      in CH2Cl2. In the presence of F(-), the desilylation of trimethylsilyl ether
      caused decay of the excimer emission as well as enhancement of the monomer
      emission to give a ratiometric signal. The fluoride-triggered desilylation showed
      a high reaction rate and high affinity to F(-) over nine other interfering
      anions. ES-1 provided a novel fluorescence assay based on excimer-monomer switch
      of N-aryl-1,8-naphthalimide to quantitatively measure F(-) with a detection limit
      of 0.133 ppm. 

PMID- 24867477
TI  - Learning to deal constructively with troubled conscience related to care
      providers' perceptions of deficient teamwork in residential care of older people-
      a participatory action research study.
AB  - Conscience can be perceived as an asset that helps care providers to provide good
      care, but it can also be a burden that generates stress of conscience (stress
      related to a troubled conscience). Participatory action research (PAR) has been
      shown to be successful in supporting care providers in residential care of older
      people to learn to deal with their troubled conscience in challenging and
      demanding care situations. The aim of the study was to describe an intervention
      process to assist care providers in residential care of older people to
      constructively deal with their troubled conscience related to perceptions of
      deficient teamwork. The study design was grounded in PAR. Nine enrolled nurses
      (ENs), two nursing aids (NAs), one Registered Nurse (RN) and their manager
      participated in 12 PAR sessions. All sessions were tape-recorded, and a domain
      analysis of the transcriptions was performed. Findings show that a PAR-based
      intervention can support care providers to understand, handle and take measures
      against deficient teamwork. Using troubled conscience as a driving force can
      increase the opportunities to improve quality of care in residential care for
      older people. During the PAR process, participants raised their awareness of the
      need to view the team in a wider sense and that the manager and the Registered
      Nurse should also be members of the team to improve team outcome. To improve
      clinical practice, we suggest that teams in residential care of older people
      should be enabled to share and reflect on challenging situations that generate
      troubled conscience. However, as shown in this study, care providers might need
      support in order to facilitate and promote sharing and reflecting on what their
      conscience tells them. 

PMID- 24867479
TI  - Up to date epidemiology, diagnosis and management of invasive fungal infections.

PMID- 24867481
TI  - [Thrombosis in ovarian hyperstimulation syndrome].
AB  - BACKGROUND: Ovarian hyperstimulation syndrome is a rare complication of IVF
      treatment. In severe ovarian hyperstimulation syndrome there is an increased risk
      of thrombo-embolic events. Venous thrombotic complications tend to occur several
      weeks after the resolution of ovarian hyperstimulation syndrome. Predominant
      sites of venous thrombosis in OHSS are the upper extremities. CASE DESCRIPTION: A
      34-year old woman presented to the emergency department with complaints about a
      painful swelling in the neck and a bluish discoloration of the right arm. She had
      been admitted to the hospital six weeks before, because of shortness of breath
      from pleural effusion due to ovarian hyperstimulation syndrome. The diagnosis of
      jugular vein and subclavian vein thrombosis was made. She was treated with
      therapeutic doses of low-molecular-weight heparin. CONCLUSION: Venous thrombosis
      is a rare but serious complication of ovarian hyperstimulation syndrome. For
      patients who require admission because of severe ovarian hyperstimulation
      syndrome, thromboprophylaxis should be continued several weeks after discharge.

PMID- 24867482
TI  - [Inventory of attendance at Dutch emergency departments and self-referrals].
AB  - OBJECTIVE: To make an inventory of annual attendance at emergency departments
      (A&E) in the Netherlands. DESIGN: Inventorisation study in all Dutch A & E
      departments. METHOD: All A& E departments in the Netherlands that were
      operational for 24 hours a day, 7 days a week in December 2012 were approached (n
      = 93) and the following data were collected over 2012: the total number of
      patients, the number of hospital admissions through the A & E department, and the
      number of self-referrals. RESULTS: Data were obtained from 96% emergency
      departments (n = 89) throughout the Netherlands, including all 8 university
      medical centres and 28 hospitals of the association of tertiary medical teaching
      hospitals (STZ). In 2012 a total of 1,989,746 people attended the 89 emergency
      departments. The average percentage of hospital admissions from an A & E
      department was 32% nationwide (range: 8-54). The average percentage of self
      referrals to the emergency departments was 30% nationwide (range: 3-76).
      CONCLUSION: The number of attendees at A & E, the admission rate through the A &
      E department and percentage of self-referrals in 2012 showed a range of variation
      nationwide. The number of people attending A & E has not increased over the last
      few years and is low in international terms. On average one-third of people
      attending A & E were admitted. In contrast with prevailing national beliefs,a
      minority of attendees at A &E departments were self-referrals.

PMID- 24867480
TI  - [Timing of elective term caesarean sections; trends in the Netherlands].
AB  - OBJECTIVE: To analyse if from 2000-2010 the rate of elective caesarean sections
      (CS) before 39 0/7 weeks of gestation declined when compared with all elective
      CS, and to evaluate the possible associated factors. DESIGN: Retrospective cohort
      study. METHOD: Using data from The Netherlands Perinatal Registry, all term
      elective CS (n = 59,653) from 2000-2010 were selected. Trends in patient
      characteristics and in performing an elective CS before 39 0/7 weeks were
      analysed using regression analysis, and differences between hospitals using the
      chi2 test. Using multiple logistic regression analysis it was analysed which
      factors were associated with performing an elective CS before 39 0/7 weeks.
      RESULTS: The percentage of elective CS before 39 0/7 weeks decreased from 56% in
      2000 to 43% in 2010 (p < 0.0001). In peripheral hospitals an elective SC was
      performed more often before 39+0 weeks than in academic hospitals; 53% in
      peripheral teaching hospitals, 57% in peripheral non-teaching hospitals, and 46%
      in academic hospitals. Adjusted odds ratios and 95% confidence intervals were
      1.38 (1.30-1.47) in peripheral teaching hospitals, and 1.55 (1.46-1.65) in
      peripheral non-teaching hospitals. In hospitals where the number of deliveries
      per year was situated in the lower quartile, elective CS before 39 0/7 weeks was
      carried out more often than in hospitals where deliveries per year were in the
      upper quartile, 60% versus 52% (p < 0.0001). CONCLUSION: In the period 2000-2009
      the timing of elective CS improved marginally. In 2010 the trend began to
      decline, even though 43% of elective caesarean sections were still carried out
      before 39 0/7 weeks. This results in a higher risk of neonatal morbidity and
      health problems in long-term.

PMID- 24867483
TI  - [A patient in a methoxetamine-induced dissociative psychosis].
AB  - BACKGROUND: The international drug market has dramatically changed with the
      emergence of various new psychoactive substances that are mostly being sold on
      the internet. One of those new psychoactive substances is methoxetamine (MXE), a
      structural analogue of ketamine. CASE DESCRIPTION: A 30-year-old man with no
      history of illness was presented to the accident and emergency department. He had
      lost his balance and could not move. He was in a dissociative psychosis, felt he
      had no control over his body and was extremely frightened. Most of this symptoms
      disappeared within two hours of arrival. The next day there were no indications
      of a psychosis, and only headache and nausea remained. The state of dissociative
      psychosis was caused by MXE, which was sold to him as an ecstasy tablet.
      CONCLUSION: Whether mixed with alcohol and other drugs or not, MXE can cause
      serious feelings of dissociation resulting in extreme anxiety and psychosis. This
      might cause severely lowered consciousness in these patients. Currently, use of
      MXE in the Netherlands is limited, but ketamine or MXE intoxication should be
      considered in patients with these symptoms.

PMID- 24867484
TI  - [An 84 year old man with gastric outlet obstruction].
AB  - An 84-year-old man was admitted with 4 days of postprandial emesis. Gastroscopy
      revealed the presence of a large gallstone in the duodenal bulb causing gastric
      outlet obstruction. The patient was diagnosed with Bouveret's syndrome. Treatment
      consisted of gastrotomy with removal of the gallstone. 

PMID- 24867485
TI  - [Hospital standardized mortality ratios: a topsy-turvy world].
AB  - Hospital standardized mortality ratios (HSMR) are meant to compare mortality
      risks between hospitals. There is, however, much discussion about the value of
      the HSMR because incomplete adjustment for case mix is almost inevitable and
      because the data required to estimate HSMR are often unreliable. There is also a
      further problem with HSMR, which hampers its interpretation: the starting point
      for the HSMR is a comparison between the mortality outcomes of more than 50
      common diagnoses, not between one or two well-defined treatments for one disease.
      The number of factors that can influence mortality risk in a hospital for these
      50 diagnoses is enormous. There are many potential explanations for an increased
      (or decreased) HSMR, meaning that even if an increased HSMR really does point
      towards an increased mortality risk, this provides no real indication of the
      underlying cause. 

PMID- 24867486
TI  - Bayesian tests to quantify the result of a replication attempt.
AB  - Replication attempts are essential to the empirical sciences. Successful
      replication attempts increase researchers' confidence in the presence of an
      effect, whereas failed replication attempts induce skepticism and doubt. However,
      it is often unclear to what extent a replication attempt results in success or
      failure. To quantify replication outcomes we propose a novel Bayesian replication
      test that compares the adequacy of 2 competing hypotheses. The 1st hypothesis is
      that of the skeptic and holds that the effect is spurious; this is the null
      hypothesis that postulates a zero effect size, H0 : delta = 0. The 2nd hypothesis
      is that of the proponent and holds that the effect is consistent with the one
      found in the original study, an effect that can be quantified by a posterior
      distribution. Hence, the 2nd hypothesis-the replication hypothesis-is given by Hr
      : delta ~ "posterior distribution from original study." The weighted-likelihood
      ratio between H0 and Hr quantifies the evidence that the data provide for
      replication success and failure. In addition to the new test, we present several
      other Bayesian tests that address different but related questions concerning a
      replication study. These tests pertain to the independent conclusions of the
      separate experiments, the difference in effect size between the original
      experiment and the replication attempt, and the overall conclusion based on the
      pooled results. Together, this suite of Bayesian tests allows a relatively
      complete formalization of the way in which the result of a replication attempt
      alters our knowledge of the phenomenon at hand. The use of all Bayesian
      replication tests is illustrated with 3 examples from the literature. For
      experiments analyzed using the t test, computation of the new replication test
      only requires the t values and the numbers of participants from the original
      study and the replication study.

PMID- 24867487
TI  - Saccade-like behavior in the fast-phases of optokinetic nystagmus: an
      illustration of the emergence of volitional actions from automatic reflexes.
AB  - As a potential exemplar for understanding how volitional actions emerged from
      reflexes, we studied the relationship between an ancient reflexive gaze
      stabilization mechanism (optokinetic nystagmus [OKN]) and purposeful eye
      movements (saccades) that target an object. Traditionally, these have been
      considered distinct (except in the kinematics of their execution) and have been
      studied independently. We find that the fast-phases of OKN clearly show
      properties associated with saccade planning: (a) They are characteristically
      delayed by irrelevant distractors in an indistinguishable way to saccades (the
      saccadic inhibition effect), and (b) horizontal OKN fast-phases produce curvature
      in vertical targeting saccades, just like a competing saccade plan. Thus, we
      argue that the saccade planning network plays a role in the production of OKN
      fast-phases, and we question the need for a strict distinction between eye
      movements that appear to be automatic or volitional. We discuss whether our
      understanding might benefit from shifting perspective and considering the entire
      "saccade" system to have developed from an increasingly sophisticated OKN system.

PMID- 24867489
TI  - [Disinfection and recontamination of rigid endoscopes: improved safety using an
      immersion quiver system].
AB  - BACKGROUND: In Otorhinolaryngology, rigid endoscopes are used daily at a high
      frequency. There is no consensus for reprocessing these medical instruments.
      Often immersion disinfection procedures are used. The present study examined the
      possible risk of recontamination by this disinfection method and investigated the
      possibility of avoiding this risk by using a new immersion quiver system.
      METHODS: Using coloured markers, a possible contact of the endoscope with the top
      edges of quivers of different diameters during endoscope removal was tested for.
      In addition, it was evaluated whether Staphylococcus aureus transfer is possible
      via this route. The same methodology was applied to a new immersion quiver
      system. RESULTS: Whenever removing the rigid endoscopes from the conventional
      quiver, these touched the top of the quiver, regardless of its diameter. A
      transfer of Staphylococcus aureus from the quiver to the endoscope via this route
      could be detected in five out of eight attempts. During endoscope removal from
      the new immersion quiver system, no contact of the endoscope with the outer
      quiver occurred in 20 passes. In none of eight trials was a transfer of
      Staphylococcus aureus from previously contaminated immersion quivers to the
      endoscope shown; all immersion quivers were sterile after disinfection.
      DISCUSSION: After conventional immersion disinfection, recontamination of rigid
      endoscopes by a contaminated quiver edge is possible. An immersion quiver system
      can resolve this risk of recontamination easily, by decontaminating not only the
      endoscope, but also the immersion quiver (inner quiver) itself in the
      disinfectant solution.

PMID- 24867490
TI  - Catalytic depolymerization of lignin in supercritical ethanol.
AB  - One-step valorization of soda lignin in supercritical ethanol using a CuMgAlOx
      catalyst results in high monomer yield (23 wt%) without char formation. Aromatics
      are the main products. The catalyst combines excellent deoxygenation with low
      ring-hydrogenation activity. Almost half of the monomer fraction is free from
      oxygen. Elemental analysis of the THF-soluble lignin residue after 8 h reaction
      showed a 68% reduction in O/C and 24% increase in H/C atomic ratios as compared
      to the starting Protobind P1000 lignin. Prolonged reaction times enhanced lignin
      depolymerization and reduced the amount of repolymerized products. Phenolic
      hydroxyl groups were found to be the main actors in repolymerization and char
      formation. 2D HSQC NMR analysis evidenced that ethanol reacts by alkylation and
      esterification with lignin fragments. Alkylation was found to play an important
      role in suppressing repolymerization. Ethanol acts as a capping agent,
      stabilizing the highly reactive phenolic intermediates by O-alkylating the
      hydroxyl groups and by C-alkylating the aromatic rings. The use of ethanol is
      significantly more effective in producing monomers and avoiding char than the use
      of methanol. A possible reaction network of the reactions between the ethanol and
      lignin fragments is discussed.

PMID- 24867488
TI  - Central and peripheral components of working memory storage.
AB  - This study reexamines the issue of how much of working memory storage is central,
      or shared across sensory modalities and verbal and nonverbal codes, and how much
      is peripheral, or specific to a modality or code. In addition to the exploration
      of many parameters in 9 new dual-task experiments and reanalysis of some prior
      evidence, the innovations of the present work compared to previous studies of
      memory for 2 stimulus sets include (a) use of a principled set of formulas to
      estimate the number of items in working memory and (b) a model to dissociate
      central components, which are allocated to very different stimulus sets depending
      on the instructions, from peripheral components, which are used for only 1 kind
      of material. We consistently find that the central contribution is smaller than
      was suggested by Saults and Cowan (2007) and that the peripheral contribution is
      often much larger when the task does not require the binding of features within
      an object. Previous capacity estimates are consistent with the sum of central
      plus peripheral components observed here. We consider the implications of the
      data as constraints on theories of working memory storage and maintenance.

PMID- 24867493
TI  - Distribution of glutathione peroxidase 1 in liver tissues of healthy and diabetic
      rats treated with capsaisin.
AB  - We investigated the immunohistochemical localization of glutathione peroxidase 1
      (GPx 1) and the structural changes that occur in the livers of healthy and
      diabetic rats that were treated with capsaisin (CAP). Fifty female rats were
      divided into five groups: group 1, sham; group 2, untreated control; group 3, CAP
      treated; group 4, streptozotocin (STZ) diabetic; group 5, STZ diabetic + CAP
      treated. STZ was administered to groups 4 and 5; after verifying diabetes, CAP
      was administered daily for 2 weeks to groups 3 and 5. Diffuse, microvesicular and
      some macrovesicular fatty degeneration were observed in the cytoplasms of
      hepatocytes in the livers of the diabetic group. In the CAP-treated diabetic
      group, fat degeneration in the livers decreased slightly by day 7. Irregularity
      of the external contours of nuclei of the hepatocytes, swelling of the nuclei,
      and slight anisocytosis and anisokaryosis were observed in the hepatocytes of the
      diabetic group. In the CAP-treated diabetic groups, the severity of anisocytosis
      and anisokaryosis decreased slightly by day 7. In all groups, GPx 1 showed
      similar immunolocalization, but in the diabetic and diabetic + CAP groups, GPx 1
      immunoreactivity was less than in the other groups. GPx 1 immunoreactivity in the
      CAP-treated diabetic group was weaker than in the diabetic group. In all groups,
      GPx 1 immunoreactivity was diffusely cytoplasmic in some of the hepatocytes, and
      diffusely cytoplasmic and diffusely nuclear in other hepatocytes. Also, GPx 1
      immunoreactivity in the liver was more intense in the hepatocytes around
      Kiernan's space. We found that CAP caused a decrease in GPx 1.

PMID- 24867494
TI  - Quirks of dye nomenclature. 3. Trypan blue.
AB  - Trypan blue is colorant from the 19(th) century that has an association with
      Africa as a chemotherapeutic agent against protozoan (Trypanosomal) infections,
      which cause sleeping sickness. The dye still is used for staining biopsies,
      living cells and organisms, and it also has been used as a colorant for textiles.

PMID- 24867491
TI  - A map of dielectric heterogeneity in a membrane protein: the hetero-oligomeric
      cytochrome b6f complex.
AB  - The cytochrome b6f complex, a member of the cytochrome bc family that mediates
      energy transduction in photosynthetic and respiratory membranes, is a hetero
      oligomeric complex that utilizes two pairs of b-hemes in a symmetric dimer to
      accomplish trans-membrane electron transfer, quinone oxidation-reduction, and
      generation of a proton electrochemical potential. Analysis of electron storage in
      this pathway, utilizing simultaneous measurement of heme reduction, and of
      circular dichroism (CD) spectra, to assay heme-heme interactions, implies a
      heterogeneous distribution of the dielectric constants that mediate electrostatic
      interactions between the four hemes in the complex. Crystallographic information
      was used to determine the identity of the interacting hemes. The Soret band CD
      signal is dominated by excitonic interaction between the intramonomer b-hemes, bn
      and bp, on the electrochemically negative and positive sides of the complex.
      Kinetic data imply that the most probable pathway for transfer of the two
      electrons needed for quinone oxidation-reduction utilizes this intramonomer heme
      pair, contradicting the expectation based on heme redox potentials and
      thermodynamics, that the two higher potential hemes bn on different monomers
      would be preferentially reduced. Energetically preferred intramonomer electron
      storage of electrons on the intramonomer b-hemes is found to require
      heterogeneity of interheme dielectric constants. Relative to the medium
      separating the two higher potential hemes bn, a relatively large dielectric
      constant must exist between the intramonomer b-hemes, allowing a smaller
      electrostatic repulsion between the reduced hemes. Heterogeneity of dielectric
      constants is an additional structure-function parameter of membrane protein
      complexes. 

PMID- 24867495
TI  - Cytomorphometric analysis of oral submucous fibrosis and leukoplakia using methyl
      green-pyronin Y, Feulgen staining and exfoliative brush cytology.
AB  - The incidence of potentially malignant oral pathology such as leukoplakia, oral
      submucous fibrosis and squamous cell carcinoma has increased in India. We
      investigated whether cytoplasmic diameter, nuclear diameter and nucleus:cytoplasm
      ratio in exfoliative cytology are reliable indicators of potentially malignant
      lesions. We also investigated methyl green-pyronin Y and Feulgen staining as
      simple time saving and cost effective staining techniques for diagnostic
      exfoliative cytology. Cell and nuclear diameters of squamous cells of normal
      buccal mucosa, oral leukoplakia and oral submucous fibrosis were measured using
      an ocular micrometer disc. The nucleus:cytoplasm ratios in pathological cells
      were compared to age, sex and site matched controls. We found a significant
      reduction in the mean cytoplasmic and nuclear diameter in the experimental groups
      compared to normal controls. Methyl green-pyronin Y stained smears were clearer
      than Feulgen stained cells. We suggest that a decreased mean cytoplasmic diameter
      of exfoliated buccal mucosal cells could serve as an early indicator of
      dysplastic change in lesions that otherwise appear benign. Methyl green-pyronin Y
      may be useful for identifying premalignant and malignant transformations before a
      lesion is visible. The simplicity of the technique makes its routine use
      feasible.

PMID- 24867496
TI  - The cytotoxic, neurotoxic, apoptotic and antiproliferative activities of extracts
      of some marine algae on the MCF-7 cell line.
AB  - Abstract We investigated the cytotoxic, neurotoxic, apoptotic and
      antiproliferative effects of extracts from Petalonia fascia, Jania longifurca and
      Halimeda tuna on the MCF-7 breast cancer cell line. J. longifurca extracts were
      more toxic than those of P. fascia and H. tuna. The algal extracts showed
      significant toxic effects at different dilutions. The toxic effects were due to
      increased oxidative stress and resulted in apoptosis. Algal toxicity may exert
      negative effects through the food chain or by direct interaction. Algal toxicity
      also has potential for cancer therapy. The toxic effects that we observed may be
      especially important for therapy for breast tumors. 

PMID- 24867497
TI  - Acute toxic effects of single dose dacarbazine: hematological and histological
      changes in an animal model.
AB  - Treatment of advanced soft tissue sarcoma usually includes dacarbazine (DTIC), an
      alkylating agent that methylates DNA and is active during all phases of the cell
      cycle. Common side effects of DTIC include nausea, vomiting, impaired liver and
      kidney function, myelosuppression, and pneumonia. There are no accounts, however,
      of histological and hematological changes caused by DTIC. We investigated acute
      hematological and morphological changes in different organs and in tumors that
      were caused by a single dose of DTIC. Adult Syrian golden hamsters were
      inoculated with a suspension of tumorigenic baby hamster kidney (BHK) cells by
      subcutaneous injection. On day 14 after inoculation, doses of 1.4, 1.6, 1.8 or
      2.0 g/m(2) DTIC were injected intraperitoneally into the hamsters. Hamsters in
      the control group were injected with physiological saline in the same way. Seven
      days after drug or saline injection the animals were sacrificed and samples of
      blood, heart, kidney, liver, lungs, spleen, small intestine and tumor were
      excised, processed and analyzed. Mitoses were counted using an ocular extension
      with engraved frame. Anemia, thrombocytopenia and leukocytosis were found in the
      control group of hamsters with fibrosarcoma, whereas animals with fibrosarcoma
      treated with DTIC developed anemia, thrombocytopenia and leukopenia. Severe
      pneumonia and moderate hepatitis were detected in all DTIC treated groups.
      Effects of DTIC on tumor cells included rounding and enlargement of nuclei and
      rarefaction of chromatin. The number of mitoses was reduced with increasing doses
      of DTIC. Hepatitis, myelosuppression, pneumonia, and dose-related inhibition of
      tumor cell proliferation were observed after a single dose of DTIC.

PMID- 24867503
TI  - Hepatoprotective and antioxidant activity of N-Trisaccharide in different
      experimental rats.
AB  - OBJECTIVES: To investigate the hepatoprotective, antioxidant and
      antihyperlipidemic effect of N-Trisaccharide isolated from Cucumis prophetarum
      (L.) on different experimental rats. METHODS: N-Trisaccharide (25 and 50
      mg/kg.b.w), silymarin (25 mg/kg) and glibenclamide (25 mg/kg) was orally
      administered once daily for 28 days and toxicity evaluation studies were carried
      out. Liver damage was assessed by determining DNA damage, serum enzyme activities
      and hepatic histopathology of carbon tetrachloride (CCl4) induced hepatic injury
      in rats. Enzymatic and non enzymatic antioxidant levels in liver and kidney were
      determined and biochemical parameters such as, serum lipid profile, renal
      function markers were estimated in type 2 diabetic rats. RESULTS: DNA
      fragmentation analysis revealed the protective effect of N-Trisaccharide on liver
      DNA damage. Histopathological studies indicated that CCl4-induced liver injury
      was less severe in N-Trisaccharide (25 and 50mg/kg) treated group. Given at the
      above doses conferred significant protection against the hepatotoxic actions of
      CCl4 in rats, reducing serum markers like SGOT, SGPT, ALP, creatinine and urea
      levels back to near normal (p<0.05) compared to untreated rats. In diabetic rats,
      N-Trisaccharide treatment significantly reversed abnormal status of enzymatic and
      non-enzymatic antioxidants levels to near normal. Also, serum lipids such as TG,
      TC, LDL-C and VLDL-C levels were significantly (p<0.05) reduced compared to
      diabetic untreated rats. CONCLUSION: Present study results confirm that N
      Trisaccharide possesses significant antihyperlipidemic, antioxidant and
      hepatoprotective properties.

PMID- 24867505
TI  - Evaluation of the new red cell parameters on Beckman Coulter DxH800 in
      distinguishing iron deficiency anaemia from thalassaemia trait.
AB  - INTRODUCTION: The new red blood cell (RBC) parameters such as reticulocyte
      haemoglobin content and percentage of hypochromic red cells or equivalent,
      although useful in the laboratory assessment of iron deficiency anaemia (IDA),
      are confounded by thalassaemia trait (TT). We aim to evaluate the new red cell
      parameters on the Beckman Coulter DxH800 in distinguishing between IDA and TT.
      METHODS: A total of 246 normal subjects, 102 patients with IDA and 115 subjects
      with TT were accrued for the study. The parameters studied were red blood cell
      size factor (RSF), low haemoglobin density (LHD%), microcytic anaemia factor
      (MAF), standard deviation of conductivity of the nonreticulocyte population (SD-C
      NRET) and unghosted cell (UGC). Comparison between groups was performed by
      Student's t-test, and the diagnostic performance was determined by receiver
      operating characteristic (ROC) curve analysis. RESULTS: Both the LHD% and RSF
      were significantly higher in IDA than TT, whereas MAF and SD-C-NRET were
      significantly lower. The SD-C-NRET showed the best diagnostic performance as a
      single parameter. A formula, [(RBC + Hb) * (HCT + SD-C-NRET)]/RDW-SD, was devised
      to distinguish between IDA and TT. With a cut-off value of 23, the area under the
      curve (AUC) was 0.995 (95% CI of 0.99-1.00), the sensitivity was 97%, and the
      specificity was 99.1%. CONCLUSIONS: The new RBC parameters on Beckman Coulter
      DxH800 provide useful information in distinguishing between IDA and TT, which is
      important for clinical decision-making and for streamlining laboratory testing. A
      new formula is devised that performs better than other discriminant functions in
      the literature.

PMID- 24867504
TI  - Toxic hepatitis induced by a herbal medicine: Tinospora crispa.
AB  - Herbal remedies are becoming increasingly popular in many countries. Tinospora
      species (Menispermaceae) is commonly used as a herbal medicine in South Asia, but
      very few toxic effects have been described. We report a case of acute hepatitis
      associated with chronic use of high doses of Tinospora crispa. A 49-year-old male
      with chronic low back pain bought a herbal medicine at a market in Vietnam that
      was supposed to be Tinospora crispa, and started to take 10 pellets per day. He
      had no medical history and did not take any other drugs or toxins. Four weeks
      later; he developed dark urine and pale stools, associated with asthenia and
      right hypochondrial pain. Two months after starting treatment, he was referred to
      the hepatology department with jaundice. Blood tests showed aspartate
      aminotransferase: 1.169 IU/l, alanine aminotransferase: 2.029 IU/l, total
      bilirubin: 20.47 mg/dl, direct bilirubin: 13.29 mg/dl, and gamma
      glutamyltransferase: 243 IU/l. Viral and autoimmune hepatitis were eliminated.
      Upper abdominal ultrasound was normal. Histopathological findings were consistent
      with a toxic reaction. The herbal medicine was stopped on admission and the
      patient fully recovered without treatment, with normal liver function 2 months
      after the acute episode. Tinospora crispa was clearly identified in the pellets
      by microscopic analysis of the botanical characters combined with chromatographic
      fingerprints. The use of herbal medicines containing Tinospora crispa can induce
      toxic hepatitis. Recovery can be complete after discontinuation. This case
      highlights the risk associated with traditional herbal remedies.

PMID- 24867506
TI  - Regulation of insulin secretion by geniposide: possible involvement of
      phosphatidylinositol 3-phosphate kinase.
AB  - AIM: Type 2 diabetes mellitus is characterized by lack of, or relative deficiency
      in, insulin productions and insensitivity of target tissues to insulin.
      Improvement of beta-cell functions is a potential strategy for the clinical
      management of this disease. We reported before that geniposide improved glucose
      stimulated insulin secretion with the activation of glucagon-like peptide 1
      receptor (GLP-1R) in INS-1 pancreatic beta cells, but the cell signaling
      mechanism of geniposide regulating glucose-stimulated insulin secretion (GSIS) in
      beta cells is so far poorly understood. MATERIALS AND METHODS: Effect of
      LY294002, a specific inhibitor of PI3K, on GSIS in the presence or absence of
      geniposide in INS-1 cells. In addition, the differential protein expression of
      geniposide treated INS-1 cells was examined by Western blot. RESULTS: After
      pretreatment with 10 uM LY294002 for 1 hour, the insulin secretion induced by
      geniposide was partly abolished in INS-1 cells. After treatment with geniposide,
      the phosphorylation of PDK1 and Akt473 increased gradually to the maximum at 60
      minutes or 120 minutes respectively. Furthermore, geniposide also inhibited the
      phosphorylation of downstream target GSK3beta, and this effect was counteracted
      by preincubation with LY294002. And the expression of GLUT2 was increased after
      treatment with different doses geniposide. CONCLUSIONS: Geniposide increases
      insulin secretion in pancreatic beta cells in a PI3K dependent mechanism
      potentially through increased GLUT2 protein levels.

PMID- 24867507
TI  - Is it time to revise the normal range of serum uric acid levels?
AB  - The actual reference range of serum uric acid has been assessed according to its
      variations among healthy individuals. i.e. those without clinical evidence of
      gout. By this approach, serum uric acid values between 3.5 and 7.2 mg/dL in adult
      males and postmenopausal women and between 2.6 and 6.0 mg/dL in premenopausal
      women have been identified as normal in many countries. However, this definition
      of normal range of serum uric acid in the general population is inevitably
      influenced by what we consider as "normal", since the absence of gout flares does
      not necessarily imply the absence of uric acid-related damage. Indeed, a growing
      body of evidence indicates that silent deposition of monosodium urate crystals as
      a result of hyperuricaemia may occur and lead to early destructive skeletal
      changes. In addition, a growing body of evidences demonstrates that uric acid
      might play a pathophysiological role in many "cardio-nephro-metabolic" disorders,
      which seems to be independent of the deposition of monosodium urate crystals,
      since it is evident also for serum uric acid concentrations below the saturation
      point for monosodium urate. Taken together, these findings strongly suggest to
      carefully reconsider the concept of "asymptomaticity" for chronic hyperuricemia
      and to consequently revise the normal range of serum uric acid levels also
      considering the progressive worldwide increase of circulating levels of uric
      acid, which could lead to a "shift to right" (i.e. toward higher values) of
      normal range. In the light of the new scientific knowledge on the
      pathophysiological role of uric acid in human disease, a threshold value < 6.0
      mg/dL (< 360 umol/L) seems to better identify true "healthy subjects" and should
      reasonably be considered for all subjects. 

PMID- 24867508
TI  - Effect of pioglitazone on expression of hypoxia-inducible factor 1alpha and
      vascular endothelial growth factor in ischemic hindlimb of diabetic rats.
AB  - OBJECTIVE: To observe effects of the drug pioglitazone on expression of hypoxia
      inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor
      (VEGF) in diabetic rats with hindlimb ischemia, and explore the role of
      pioglitazone in angiogenesis after ischemia and its possible mechanism. MATERIALS
      AND METHODS: The diabetic rat model was established by high-fat and high-sugar
      diet and intraperitoneal injection of streptozotocin. The diabetic rats with the
      unilateral hindlimb ischemia were randomly divided into diabetic model group and
      pioglitazone treated group, and the normal rats with unilateral hindlimb ischemia
      were selected as the control group. RT-PCR and Western blotting techniques were
      employed for analysis and detection of HIF-1alpha and VEGF expression, as well as
      detection of capillary density by immunohistochemical staining and ischemic
      hindlimb perfusion by Doppler ultrasonography were measured. RESULTS: Compared
      with the control group, the fasting glucose, fasting insulin, insulin resistance
      index, total cholesterol, triglycerides and low-density lipoprotein cholesterol
      in diabetic rats were significantly increased. This was accompanied by increased
      mRNA and protein expression of HIF-1alpha and VEGF, and decreased microvessel
      density (MVD) of the ischemic limb (p < 0.05). The above indicators in
      pioglitazone-treated diabetic rats were significantly decreased (p < 0.01) with
      decreased expression of HIF-1alpha and VEGF (p < 0.01), while the microvessel
      density (MVD) of the ischemic limb was increased (p < 0.01) and blood perfusion
      was also increased (p < 0.01). The expression of HIF-1alpha and VEGF were
      positively correlated (p < 0.05) in diabetic rats with hind limb angiopathy,
      while HIF-1alpha and VEGF were all negatively correlated with the microvessel
      density (MVD). CONCLUSIONS: HIF-1alpha and VEGF expression in diabetic rats with
      hind limb angiopathy were increased. Pioglitazone has a promoting effect on
      ischemic limb angiogenesis in diabetic rats. It suggested that pioglitazone may
      improve ischemic limb angiogenesis mechanisms correlated with regulating the HIF
      1alpha/VEGF hypoxia response pathway.

PMID- 24867509
TI  - Correlative study on risk factors of depression among acute stroke patients.
AB  - BACKGROUND: The causes of post-stroke depression (PSD) were complex, and it is
      hard to identify the consistent risk factors because the correlation may change
      along with time. AIM: To study the prevalence and multiple correlation factors of
      PSD in acute stroke patients. PATIENTS AND METHODS: The patients within over 2-6
      weeks after stroke were collected and divided into depression group, depressive
      symptom group, and control group according to the Hamilton Depression Rating
      Scale for Depression. The NIH (National Institute of Health) Stroke Scale, the
      Barthel index (BI), the Instrumental Activities of Daily Living (IADL), and the
      Mini-Mental State Examination (MMSE) were respectively used to evaluate the
      neurologic impairment, Ability of Daily Life, and cognitive function of patients.
      RESULTS: PSD was associated with lower incomes (p < 0.05), but not associated
      with education level, medical insurance, and nature of the acute stroke (p >
      0.05). The lesion location in the left hemisphere of the brain had a higher
      morbidity than that in the right hemisphere or both sides. There was a
      significant difference in the incidence of PSD between multifocal lesions and
      single lesion (p < 0.01). CONCLUSIONS: Lower income, cognitive dysfunctions, poor
      activities of daily life, poor social support, and history of hypertension and
      previous stroke were risk factors for the acute stroke patients to get
      depression. Stroke survivors with left hemisphere of the brain and more lesions
      (>= 2) have more chance to get the PSD.

PMID- 24867511
TI  - Use of entecavir for the treatment of complex forms of hepatitis B.
AB  - INTRODUCTION: Although most HBV infections are effectively managed by the
      available therapies, the treatment of the most complex cases of hepatitis B still
      represents an unmet medical need. Entecavir is considered a first-line
      therapeutic option for hepatitis B, due to its demonstrated efficacy in rapidly
      suppressing the viral load. Its activity is also characterized by a high genetic
      barrier and an overall favorable safety profile. AIM: This review provides an
      overview of the most recent evidence related to the use of entecavir in the
      management of the most complex forms of hepatitis B. MATERIALS AND METHODS:
      Original articles for inclusion in this review were retrieved from online
      databases such as PubMed/Medline and EMBASE; their reference list was browsed to
      found other relevant papers. The identified papers were selected for inclusion in
      the present manuscript according to their relevance for the topic. The search was
      last updated on December 2013. RESULTS: Several studies have proven the efficacy
      and safety of entecavir in the treatment of patients affected by complex forms of
      hepatitis B, as those with decompensated cirrhosis, exacerbations of HBV
      infection and fulminant hepatic failure or in transplanted subjects. CONCLUSIONS:
      Overall, entecavir seems a powerful therapeutic strategy for the treatment of HBV
      infection, even in patients affected by the most complex forms of hepatitis. The
      high efficacy of entecavir, associated with its safety profile, its high genetic
      barrier to resistance and its cost-effectiveness, allowed this molecule to become
      one of the preferred first-line options of treatment to manage HBV infections.
      However, further researches and trials are still needed to definitively elucidate
      its effectiveness in the daily clinical practice.

PMID- 24867510
TI  - Mechanical thrombectomy with Solitaire stent for acute internal carotid artery
      occlusion without atherosclerotic stenosis: dissection or cardiogenic
      thromboembolism.
AB  - BACKGROUND: In acute ischemic stroke patients, internal carotid artery occlusion
      with middle cerebral artery (ICA/MCA) occlusion in succession predicts a poor
      outcome after systemic thrombolysis. It is not known whether this occlusion
      subtype of the anterior circulation is due to dissections or cardiogenic
      thromboembolism. We aimed to find useful evidence to judge the condition with
      accuracy and establish reasonable treatment protocols. PATIENTS AND METHODS: This
      retrospective study included 7 consecutive patients with acute ICA/MCA occlusion
      in succession who had undergone mechanical thrombectomy with a Solitaire stent
      retrieval between January 2012 and June 2013. Then we also reviewed the current
      literature. RESULTS: The patients had a mean age of 56 years and a mean baseline
      National Institutes of Health Stroke Scale (NIHSS) score of 20. The procedure
      resulted in thrombolysis in cerebral ischemia (TICI) scores of 2a or better in
      all patients, but complete recanalization of the ICA occlusion segment was
      achieved in only 2 patients. Stenting was not performed in all patients. At 90
      days, 1 patient was dead and 4 of the 7 patients had favorable functional
      outcomes (modified Rankin score (mRS) >= 2). We identified 9 studies with 85
      patients with nonatherosclerotic acute ICA occlusion who underwent mechanical
      thrombectomy with Solitaire stent. The mean age was 65 years with a mean baseline
      National Institute Health Stroke Scale (NIHSS) score of 16 and mean time to
      treatment of 242 minutes. The mean time of the procedures ranged from 40-160
      minutes in 9 studies. Successful recanalization was achieved in 69.4% of the
      patients and mortality was 16.5%. Favorable outcome (mRS <= 2) occurred in 42.4%
      of patients. Few studies stated whether complete recanalization was achieved in
      patients with ICA occlusion. CONCLUSIONS: Our results and the literature review
      suggest that mechanical thrombectomy in acute stroke due to ICA/MCA occlusion is
      feasible and safe, with high rates of recanalization and favorable functional
      outcomes. More patients with ICA/MCA occlusion in succession could obtain
      favorable functional outcomes with accurate judgment of the lesion location and
      appropriate treatment protocols. However, there is no consensus on how to judge
      the correct location of the ICA dissected portion and whether stenting is
      appropriate.

PMID- 24867512
TI  - A randomized double-blind placebo-controlled clinical trial on efficacy and
      safety of association of simethicone and Bacillus coagulans (Colinox(r)) in
      patients with irritable bowel syndrome.
AB  - INTRODUCTION: Irritable bowel syndrome (IBS) is a chronic gastrointestinal (GI)
      disorder that affects 15-20% of the Western population. BACKGROUND: There are
      currently few therapeutic options available for the treatment of IBS. The aim of
      this study is to evaluate the efficacy and the safety of a medical device
      containing a combination of Simethicone and Bacillus coagulans in the treatment
      of IBS. PATIENTS AND METHODS: This is a monocentric double-blind, placebo
      controlled parallel group clinical trial. Adult subjects suffering from IBS as
      defined by Rome III criteria were enrolled. Bloating, discomfort, abdominal pain
      were assessed as primary end point. Subjects received the active treatment or
      placebo 3 time a day after each meal for 4 weeks of study period. Subjects were
      submitted to visit at Day 0 (T1), at Days 14 (T2) and 29 (T3). RESULTS: Fifty-two
      patients were included into the study. Intragroup analysis showed a significant
      reduction of the bloating, discomfort and pain in Colinox(r) group (CG) compared
      to placebo group (PG). Between group analysis confirmed, at T1-T3, significant
      differences between CG and PG in bloating and discomfort. DISCUSSION: Simethicone
      is an inert antifoaming able to reduce bloating, abdominal discomfort. Literature
      offers increasing evidence linking alterations in the gastrointestinal microbiota
      and IBS and it is well known that probiotics are important to restore the native
      gut microbiota. The Colinox medical device is specifically targeted against most
      intrusive symptom of IBS (bloating) and it is also able to counteract the most
      accredited ethiopathogenetic factor in IBS (alterations of intestinal
      microbiota). CONCLUSIONS: This is the first randomized double-blind placebo
      controlled clinical trial demonstrating the efficacy and safety of a combination
      of simethicone and Bacillus coagulans in treatment of IBS.

PMID- 24867513
TI  - Transcriptome profiling of prostate tumor and matched normal samples by RNA-Seq.
AB  - BACKGROUND: RNA-Sequencing (RNA-Seq) has greatly influenced cancer researches,
      and it provides an unprecedented resolution in estimating gene expression and has
      less signal noises compared to cDNA microarray. AIM: We aimed to identify a list
      of protein-coding genes and lincRNAs that are expressed differentially between
      tumor and normal tissues. MATERIALS AND METHODS: In this study, we analyzed
      including 10 human prostate tumor tissues and their matched normal tissues
      transcriptome dataset generated by recently developed RNA-Seq technology.
      RESULTS: By aligning short reads to human RefSeq genes and lincRNAs, we
      identified 10 RefSeq genes that were differentially expressed between tumor and
      normal samples with a p-value < 0.05, which were sufficiently enough to
      distinguish these two groups. Further loosing the p-value cutoff to 0.1
      identified an lincRNA which is antisense to Cullin-associated and neddulation
      dissociated 1 (CAND1), whose expression is repressed in prostate tumor cells. By
      examining the expression of CAND1 and its antisense lincRNA in the transcriptome
      dataset, we found an interaction between them as high expression of CAND1 and low
      expression of lincRNA is normal samples, and verse visa in tumor samples.
      CONCLUSIONS: These findings suggest the important usage of RNA-Seq in cancer
      studies for biomarker development and functional investigation.

PMID- 24867514
TI  - S100A4 promotes squamous cell laryngeal cancer Hep-2 cell invasion via NF-kB/MMP
      9 signal.
AB  - OBJECTIVE: S100A4 is a member of the S100 family of calcium-binding proteins,
      which possesses a wide range of biological functions, such as regulation of
      angiogenesis, cell survival, motility, and invasion. Here, we demonstrate for the
      first time a major role of S100A4 in the cell invasion properties of the human
      laryngeal squamous carcinoma cells (LSCC) and evaluated the mechanism. MATERIALS
      AND METHODS: Cultured human LSCC cell line Hep-2 was overexpressed by
      transfection of pcDNA3.1-S100A4 plasmid. For this, cellular Hep-2 expression was
      quantified by Western blot analysis. Moreover, cell invasion and migration assays
      were performed. Furthermore, the impact of the S100A4 on NF-kB activity and MMP-9
      expression was detected. RESULTS: We found S100A4 potently promoted Hep-2
      invasion, by increasing cell motility and matrix metalloproteinase-9 (MMP-9)
      production. The increase in MMP-9 production was mediated by activation of
      nuclear factor-kB transcriptional activity by S100A4. After MMP-9 and NF-kBp65
      was inhibited by BB94 treatment and NF-kBp65 siRNA transfected, pcDNA3.1-S100A4
      induced cell invasion and migration was decreased. CONCLUSIONS: Our findings thus
      establish S100A4 as a major factor in the invasive abilities of Hep-2 cells.

PMID- 24867515
TI  - Anaplastic thyroid cancer: a case report of a long term survival patient and
      review of literature data.
AB  - Anaplastic thyroid carcinoma (ATC) is a very rare disease accounting for less
      than 2% of all thyroid malignancies and associated to a dismal prognosis. The
      median survival is between 3 to 9 months with less than 10% of patients alive at
      3 years after the time of diagnosis. This low cure rate is due to the late
      clinical presentation as a bulky unresectable tumour mass often associated with
      synchronous lung metastases (20-50%). A multimodality treatment consisting in a
      radical surgery followed by radiotherapy and chemotherapy is reported to be
      associated with better clinical outcomes while young age (< 65 years), tumour
      size (< 6.5 cm) and absence of distant metastases at time of diagnosis are
      recognized as strong prognostic factors of survival. We report the case of a 65
      year-old man who was referred to our hospital for an ATC which extended to the
      external right tracheal wall and muscolar layer of esophagus. The patient
      underwent radical thyroidectomy with bilateral neck dissection followed by 3
      cycles of adjuvant chemotherapy (Cisplatin /Epirubicin) and subsequent
      radiochemotherapy with Cisplatin as radiosensitizer. At more than 6 years since
      diagnosis the patient is still alive without evidence of local recurrence or
      distant metastases. Therefore, aggressive multimodality treatment after radical
      surgery might improve clinical outcomes and perhaps should be tested in
      prospective clinical trials. 

PMID- 24867516
TI  - Significance of the histological and ultrastructural features of elastic fibers
      in diagnosis of bronchioloalveolar carcinoma.
AB  - OBJECTIVES: The accurate identification of bronchioloalveolar carcinoma (BAC)
      from adenocarcinoma (AC) and other types of lung cancer is important from
      clinical perspectives; especially, when BAC is histologically-mixed with AC. We
      hypothesized that the elastic fibers (EF) pattern could be used as a differential
      marker to identify BAC from other lung cancers. The aim was to characterize the
      EF pattern in different types of lung cancer and evaluate its significance for
      differential diagnosis of BAC. PATIENTS AND METHODS: Clinical samples of
      different types of lung cancers were collected. The samples were stained by
      hematoxylin-eosin (H&E) staining for histopathological comparison. Then, modified
      Weigert's staining of the EF was performed to characterize its patterns. The EFs
      were semi-quantified and compared among different types of lung cancer. Further,
      transmission electronic microscopy (TEM) was performed and ultrastructural
      features of the EFs were compared between BAC and adenocarcinoma (AC). RESULTS:
      H&E staining histopathology could differentiate the most types of lung cancer
      except certain types, such as histologically-mixed BAC and AC. The EF pattern in
      BAC was uniquely different from other types of lung cancer as > 95% of BAC was +
      or ++ for EF staining while > 95% of other types of lung cancer were--or +/-
      type. TEM study further confirmed the EF pattern difference between BAC and AC.
      CONCLUSIONS: As the data show, as > 95% BAC specimens can be identified from
      other lung cancers based on EF (Weigert's) staining. The EF pattern in BAC is
      uniquely different from other types of lung cancer and, therefore, can be used as
      a differential clinical marker of BAC.

PMID- 24867517
TI  - EUS-guided fine needle tissue acquisition for the diagnosis of pleural metastases
      from endometrial cancer.
AB  - Transesophageal EUS-FNA have become a useful tool in the evaluation of the
      mediastinum, especially during the staging work-up examination of patients with
      non-small-cell lung cancer (NSCLC) or other malignancies. We report a challenging
      case of a 53 years-old woman with an endometrial adenocarcinoma who subsequently
      presented with right pleural effusion, diffuse pleural thickening with few
      pleural lesions. The patient referred a long history of exposure to amiantum,
      this posing a differential diagnosis between primary pleural tumour
      (mesothelioma) and neoplastic pleural localization of the endometrial cancer. The
      cytological examination of the pleural effusion (sampled via thoracenthesis) was
      not adequate to reach a diagnosis. Although a right-video-assisted thoracoscopy
      was considered the gold standard in this clinical setting to achieve a tissue
      acquisition of the pleura, an EUS (as the least invasive procedure) was attempted
      to reach a definitive diagnosis. EUS-FNTA of the pleura was done using a 19-Gauge
      needle and the pathological and immunophenotypic features were diagnostic for a
      pleural metastasis of high-grade endometrial serous carcinoma. The patient
      received adjuvant chemotherapy with a complete regression of the pleural lesions.
      We take the opportunity of this challenging case to discuss the efficacy and
      safety of EUS-FNAT to sample the pleural lesions with the use of a large calibre
      needle if the lesion lies just under the EUS cursor. We may assume that, in
      selected patients, this technique could be presented as a viable option to the
      more invasive surgical procedure, which has been previously the gold standard for
      the pleural tissue acquisition. 

PMID- 24867518
TI  - Dose-intensive versus dose-control chemotherapy for high-grade osteosarcoma: a
      meta-analysis.
AB  - BACKGROUND: Tumor necrosis might be a consequence of innate sensitivity of tumor
      cells to changed dosage instead of the increased dosage of chemotherapeutics in
      the treatment of osteosarcoma patients. AIM: To explore whether dose-intensive
      regimen was a better treatment method than dose-control chemotherapy for high
      grade osteosarcoma patients. MATERIALS AND METHODS: The data of the included
      studies was analyzed by random-effects model when there was heterogeneity,
      otherwise by fixed-effects method. Meta-analysis outcomes were calculated as risk
      ratio (RR) and 95% confidence interval (CI) for 5-year disease free survival
      rate, 5-year overall survival, local recurrence rate, good histological response
      rate and Limb salvage rate. RESULTS: Five studies involving 1434 patients with
      high-grade osteosarcoma were included. All the included studies were inadequate
      in the information about randomization and blinding method. The meta-analysis
      showed that there was no significant difference between the dose-intensive group
      and the dose control group in 5-year disease free survival rate (RR: 1.08, 95%
      CI: 0.96-1.21), 5-year overall survival rate (RR: 1.07, 95% CI: 0.98-1.17), good
      histological response rate (RR: 1.08, 95% CI: 0.82-1.43), limb salvage rate (RR:
      0.97, 95% CI: 0.93-1.02). However, the local recurrence rate (RR: 0.65, 95% CI:
      0.46- 0.92) and the 5-year disease free survival rate of the good and poor
      histological response (RR: 1.57, 95% CI: 1.36- 1.82) were significantly
      different. CONCLUSIONS: Dose-intensive regimen might not be a preferred treatment
      for all of the high-grade osteosarcoma patients. Although there were advantages
      in dose-intensive regimen, appropriate dosage of chemotherapy should be
      considered in clinical cases.

PMID- 24867519
TI  - Bisphosphonate-associated osteonecrosis of the jaw 2 years after teeth
      extractions: a case report solved with non-invasive treatment.
AB  - Bisphosphonates are a type of drugs known to inhibit bone resorption through
      complex interventions. Their primary mechanism of action is aimed at the cellular
      level, inhibiting osteoclast activity and, thus, bone resorption. Bisphosphonates
      are, therefore, very widely used, with many patients receiving continuous
      treatment for years. But it is well known that these drugs can produce
      osteonecrosis of the jaw and this is their principal risk. A 75-year-old woman
      received dental treatment before starting intravenous BP therapy for a breast
      cancer. She started intravenous bisphosphonate treatment with monthly protocol
      and after two years the patient presented a wound compatible with osteonecrosis
      of the jaw. 

PMID- 24867520
TI  - Assessments of jaw bone density at implant sites using 3D cone-beam computed
      tomography.
AB  - OBJECTIVE: To assess the bone density of dental implant sites using CBCT and
      Simplant software, and establish a quantitative ranges for each bone quality
      classification according to the classification of bone quality proposed by
      Lekholm and Zarb. PATIENTS AND METHODS: 128 patients' jaw bone were scanned by
      CBCT, the images were reconstructed by the Simplant software. The bone density of
      236 potential implant sites was measured and the results were recorded using
      Hounsfield units (HU).The data was analyzed with SPSS 19.0 software package for
      Mann-Whitney U test. RESULTS: The anterior mandible mean bone density was (679.6
      +/- 141.67) HU > anterior maxilla, (460.25 +/- 136.42) HU and posterior mandible,
      (394.4 +/- 128.37) HU > posterior maxilla, (229.62 +/- 144.48) HU. Quantitative
      parameters ranged of the bone density according to CBCT as follows: Lekholm and
      Zarb classification Type D4 was less than 200 HU, Type D2 and Type D3 were more
      than 200HU and less than 600 HU, and Type D1 was more than 600 HU. CONCLUSIONS:
      Anterior mandible has the highest mean bone density and posterior maxilla has the
      lowest mean bone density.It is, therefore, proposed that an objective
      classification which confirms the importance of a site-specific bone tissue
      evaluation prior to implant installation.

PMID- 24867521
TI  - Epimorphin-induced differentiation of human umbilical cord mesenchymal stem cells
      into sweat gland cells.
AB  - OBJECTIVES: Mesenchymal stem cells (MSCs) have the potential for multi
      directional differentiation and can be induced to differentiate into sweat gland
      cells under certain conditions. Epimorphin (EPM) plays an important role in the
      promotion of epithelial cell morphogenesis; however, its effect on sweat gland
      cell differentiation of MSCs remains unknown. The purpose of this study was to
      investigate how EPM regulates sweat gland cell differentiation of human umbilical
      cord mesenchymal stem cells (hUCMSCs). MATERIALS AND METHODS: hUCMSCs were
      labeled with 5-bromo-2-deoxyuridine (BrdU) before differentiation induction; were
      cultured in common culture medium, conditioned medium, or EPM-conditioned medium;
      and then induced to differentiate into sweat gland cells. Five days after
      induction, the expression rates of the sweat gland-cell antigens cytokeratin 14
      (CK14), cytokeratin 19 (CK19), and carcinoembryonic antigen (CEA) in hUCMSCs were
      detected by flow cytometry, and the messenger ribonucleic acid (mRNA) and protein
      levels of CK14, CK19, and CEA were determined by reverse transcription polymerase
      chain reaction (RT-PCR) and western blot, respectively. RESULTS: hUCMSCs can be
      induced to differentiate into sweat gland cells in conditioned medium, and
      expression of CEA was detected by immunofluorescence assay. Flow cytometry
      results showed that the expression rate of the sweat gland-cell antigens CK14,
      CK19, and CEA in the conditioned medium were significantly lower than that in the
      EPM conditioned medium (p < 0.05). RT-PCR and western blot results showed that
      the mRNA and protein levels of CK14, CK19, and CEA in the conditioned medium were
      all significantly lower than that in the EPM-conditioned medium (p < 0.01).
      CONCLUSIONS: These results suggest that EPM can effectively induce the
      differentiation of hUCMSCs into sweat gland cells.

PMID- 24867523
TI  - Chronic Mesobuthus gibbosus scorpionism related to the sting in vein.
AB  - BACKGROUND: A small amount of data is already presented in the relevant
      literature related to the medical facts of scorpionism caused by Yellow scorpion
      (Mesobuthus gibbosus: M. gibbosus). Undoubtedly, it is considered as dangerous to
      human health. This paper presents an unusual case of scorpionism after the sting
      in vein. CASE REPORT: A 25 year old male was bitten by M. gibbosus. He
      experienced extremely severe intermittent pain in the right feet, followed by
      pulsating and glowing sensations, cold sweat and paleness. 15 minutes after the
      sting, the pain started to spread through the medial side of the leg, up to the
      inguinal region. Patient became excited, and experienced occasional spasms of leg
      muscles. A month after, the bitten vein of dorsal arch of the foot and v. sephena
      magna became non-uniformly tortuously spread through the entire length. On
      physical examination four years after the sting, the enlargement of the veins
      still exists, periodical tingling, and occasional muscle twitches during the
      night. CONCLUSIONS: M. gibbosus is endemic in Mediterranean area and represents a
      real hazard for local inhabitants and tourists. The medical treatment of this
      type of scorpionism is exclusively symptomatic.

PMID- 24867524
TI  - Unilateral vestibular schwannoma associated with a Jacobson's schwannoma.
AB  - Coexistence of unilateral vestibular schwannoma and Jacobson's schwannoma growing
      in the same intracranial site is rarely observed. We present the case of 36-year
      old woman with primary diagnosis of vestibular schwannoma and subsequent
      appearance of schwannoma to the Jacobson's nerve. Initial wait and see strategy
      was performed offered us the opportunity to describe Jacobson's lesion features
      at computed tomography over a period of 4 years. Subtotal petrosectomy with
      infralabyrinthine approach was subsequently executed to remove the growing mass
      of the temporal bone. The Jacobson's schwannoma increased its size from 0.4 cm
      for years whereas vestibular schwannoma size was unchanged after 7 years
      observation. The concomitant removal of both schwannomas is still associated with
      the size of the CPA lesion and to patient's symptoms. 

PMID- 24867522
TI  - Midazolam suppresses osteogenic differentiation of human bone marrow-derived
      mesenchymal stem cells.
AB  - OBJECTIVE: Previous study showed that peripheral-type benzodiazepine receptors
      (PBRs) are expressed in human mesenchymal stem cells (hMSCs) and diazepam was
      found to inhibit hMCSs viability in high concentration. Midazolam, a
      benzodiazepine derivative, is widely used as an intravenous sedative in hospital.
      Peripheral-type benzodiazepine receptors (PBRs) affect a broad spectrum of
      cellular functions. We tested the cell viability and osteogenic differentiation
      of hMSCs. PATIENTS AND METHODS: Bone marrow was collected from 12 patients during
      the operation of spine internal fixation. Cultivated with basal medium, the
      hBMSCs were incubated with or without midazolam (0.1, 1, 5, 10, 15, 20 uM,
      respectively). Cell viability were tested with MTS assay after 2, 4, 6 hours
      respectively. Cell morphology was observed and recorded at 6 hour. After
      cultivated with osteogentic medium, the hBMSCs were incubated with or without
      midazolam (5, 10, 15, 20 uM, respectively). Alkaline phosphatase (ALP) activity
      and alizarin red S staining were measured. Cultivated with osteogentic medium
      with or without treatment of 15 uM midazolam, the mRNA expression of ALP, type 1
      collagen (COL1), Runx2 and PPARgamma was analyzed by real-time RT-PCR. RESULTS:
      The treatments of midazolam inhibited cell viability to 85%-16% respectively (p <
      0.05). Rounded up phenomenon with floating cells, Membrane-blebbed cells and
      cytoplasmic contraction were observed after 10, 15 or 20 uM midazolam treatment.
      The ALP activity and Calcium deposition of hBMSCs exposed to 15 and 20 uM
      midazolam was significantly inhibited at 7, 14 and 21 days (p < 0.05). And the
      mRNA expression of ALP, COL1 and PPARgamma was significantly suppressed in the
      hBMSCs cultured with 15 uM midazolam (p < 0.05). CONCLUSIONS: Midazolam exert
      negative effect on cell viability and osteogenic differentiation of cultured
      hBMSCs. During sedation in critical care, the use of midazolam may suppress
      activity of hBMSCs.

PMID- 24867526
TI  - Off-pump coronary artery bypass grafting in patients on chronic hemodialysis.

PMID- 24867525
TI  - RNA-Seq profiling reveals aberrant RNA splicing in patient with adult acute
      myeloid leukemia during treatment.
AB  - BACKGROUND: Multiple genetic alterations that affect the process of acute myeloid
      leukemia (AML) have been discovered, and more evidence also indicates that
      aberrant splicing plays an important role in cancer. MATERIALS AND METHODS: We
      present a RNA-Seq profiling of an AML patient with complete remission after
      treatment, to analyze the aberrant splicing of genes during treatment. We
      sequenced 3.97 and 3.32 Gbp clean data of the AML and remission sample,
      respectively. Firstly, by analyzing biomarkers associated with AML, to assist
      normal clinical tests, we confirmed that the patient was anormal karyo type, with
      NPM1 and IDH2 mutations and deregulation patterns of related genes, such as
      BAALC, ERG, MN1 and HOX family. Then, we performed alternative splicing detection
      of the AML and remission sample. RESULTS: We detected 91 differentially splicing
      events in 68 differentially splicing genes (DSGs) by mixture of isoforms (MISO).
      Considering Psi values (Psi) and confidence intervals, 25 differentially
      expressed isoforms were identified as more confident isoforms, which were
      associated with RNA processing, cellular macromolecule catabolic process and DNA
      binding according to GO enrichment analysis. An exon2-skipping event in oncogene
      FOS (FBJ murine osteosarcoma viral oncogene homolog) were detected and validated
      in this study. FOS has a critical function in regulating cell proliferation,
      differentiation and transformation. The exon2-skipping isoform of FOS was
      increased significantly after treatment. CONCLUSIONS: All the data and
      information of RNA-Seq provides highly accurate and comprehensive supplements to
      conventional clinical tests of AML. Moreover, the splicing aberrations would be
      another source for biomarker and even therapeutic target discovery. More
      information of splicing may also assist the better understanding of
      leukemogenesis.

PMID- 24867527
TI  - Is off-pump CABG really a better substitute for on-pump CABG in all cases of
      coronary artery disease?

PMID- 24867528
TI  - Assessment of whole brain white matter integrity in youths and young adults with
      a family history of substance-use disorders.
AB  - Individuals with a family history of substance use disorders (FH+) are at a
      greater risk of developing substance use disorders than their peers with no such
      family histories (FH-) and this vulnerability is proportional to the number of
      affected relatives (FH density). The risk for developing substance use disorders
      peaks during adolescence to early adulthood in the general population, and that
      is thought to be related to delayed maturation of frontocortical and
      frontostriatal functional circuits. We hypothesized that FH+ youth and young
      adults have impaired myelination of frontocortical and frontostriatal white
      matter tracts. We examined fractional anisotropy (FA) data in 80 FH+ and 34 FH-
      youths (12.9 +/- 1.0 years) and in 25 FH+ and 30 FH- young adults (24.3 +/- 3.4
      years). FH+ youths had lower FA values in both frontocortical and frontostriatal
      tracts as well as parietocortical tracts including the anterior, superior and
      posterior corona radiata and the superior frontal-occipital fasciculus. Moreover,
      FA values in these tracts were negatively correlated with FH density. FH+ adults
      had lower FA values in two frontocortical tracts: the genu of the corpus callosum
      and anterior corona radiata and also significant negative correlations between FA
      and FH density in these same tracts. In both groups, lower FA values corresponded
      to higher radial diffusivity suggesting reduced axonal myelination. We
      interpreted our findings as evidence for impaired myelination of frontal white
      matter that was proportional to FH density. Our data suggest that deficits may
      partially resolve with age, paralleling an age-related decline in risk for
      developing substance use disorders.

PMID- 24867532
TI  - Multifield optimization intensity modulated proton therapy for head and neck
      tumors: a translation to practice.
AB  - BACKGROUND: We report the first clinical experience and toxicity of multifield
      optimization (MFO) intensity modulated proton therapy (IMPT) for patients with
      head and neck tumors. METHODS AND MATERIALS: Fifteen consecutive patients with
      head and neck cancer underwent MFO-IMPT with active scanning beam proton therapy.
      Patients with squamous cell carcinoma (SCC) had comprehensive treatment extending
      from the base of the skull to the clavicle. The doses for chemoradiation therapy
      and radiation therapy alone were 70 Gy and 66 Gy, respectively. The robustness of
      each treatment plan was also analyzed to evaluate sensitivity to uncertainties
      associated with variations in patient setup and the effect of uncertainties with
      proton beam range in patients. Proton beam energies during treatment ranged from
      72.5 to 221.8 MeV. Spot sizes varied depending on the beam energy and depth of
      the target, and the scanning nozzle delivered the spot scanning treatment "spot
      by spot" and "layer by layer." RESULTS: Ten patients presented with SCC and 5
      with adenoid cystic carcinoma. All 15 patients were able to complete treatment
      with MFO-IMPT, with no need for treatment breaks and no hospitalizations. There
      were no treatment-related deaths, and with a median follow-up time of 28 months
      (range, 20-35 months), the overall clinical complete response rate was 93.3% (95%
      confidence interval, 68.1%-99.8%). Xerostomia occurred in all 15 patients as
      follows: grade 1 in 10 patients, grade 2 in 4 patients, and grade 3 in 1 patient.
      Mucositis within the planning target volumes was seen during the treatment of all
      patients: grade 1 in 1 patient, grade 2 in 8 patients, and grade 3 in 6 patients.
      No patient experienced grade 2 or higher anterior oral mucositis. CONCLUSIONS: To
      our knowledge, this is the first clinical report of MFO-IMPT for head and neck
      tumors. Early clinical outcomes are encouraging and warrant further investigation
      of proton therapy in prospective clinical trials.

PMID- 24867533
TI  - Definitive primary therapy in patients presenting with oligometastatic non-small
      cell lung cancer.
AB  - PURPOSE: Although palliative chemotherapy is the standard of care for patients
      with diagnoses of stage IV non-small cell lung cancer (NSCLC), patients with a
      small metastatic burden, "oligometastatic" disease, may benefit from more
      aggressive local therapy. METHODS AND MATERIALS: We identified 186 patients (26%
      of stage IV patients) prospectively enrolled in our institutional database from
      2002 to 2012 with oligometastatic disease, which we defined as 5 or fewer distant
      metastatic lesions at diagnosis. Univariate and multivariable Cox proportional
      hazards models were used to identify patient and disease factors associated with
      improved survival. Using propensity score methods, we investigated the effect of
      definitive local therapy to the primary tumor on overall survival. RESULTS:
      Median age at diagnosis was 61 years of age; 51% of patients were female; 12% had
      squamous histology; and 33% had N0-1 disease. On multivariable analysis, Eastern
      Cooperate Oncology Group performance status >= 2 (hazard ratio [HR], 2.43), nodal
      status, N2-3 (HR, 2.16), squamous pathology, and metastases to multiple organs
      (HR, 2.11) were associated with a greater hazard of death (all P<.01). The number
      of metastatic lesions and radiologic size of the primary tumor were not
      significantly associated with overall survival. Definitive local therapy to the
      primary tumor was associated with prolonged survival (HR, 0.65, P=.043).
      CONCLUSIONS: Definitive local therapy to the primary tumor appears to be
      associated with improved survival in patients with oligometastatic NSCLC. Select
      patient and tumor characteristics, including good performance status, nonsquamous
      histology, and limited nodal disease, may predict for improved survival in these
      patients.

PMID- 24867534
TI  - Likelihood of bone recurrence in prior sites of metastasis in patients with high
      risk neuroblastoma.
AB  - PURPOSE/OBJECTIVES: Despite recent improvements in outcomes, 40% of children with
      high-risk neuroblastoma will experience relapse, facing a guarded prognosis for
      long-term cure. Whether recurrences are at new sites or sites of original disease
      may guide decision making during initial therapy. METHODS AND MATERIALS: Eligible
      patients were retrospectively identified from institutional databases at first
      metastatic relapse of high-risk neuroblastoma. Included patients had disease
      involving metaiodobenzylguanidine (MIBG)-avid metastatic sites at diagnosis and
      first relapse, achieved a complete or partial response with no more than one
      residual MIBG-avid site before first relapse, and received no total body
      irradiation or therapy with (131)I-MIBG before first relapse. Anatomically
      defined metastatic sites were tracked from diagnosis through first relapse to
      determine tendency of disease to recur at previously involved versus uninvolved
      sites and to assess whether this pattern was influenced by site irradiation.
      RESULTS: Of 159 MIBG-avid metastatic sites identified among 43 patients at first
      relapse, 131 (82.4%) overlapped anatomically with the set of 525 sites present at
      diagnosis. This distribution was similar for bone sites, but patterns of relapse
      were more varied for the smaller subset of soft tissue metastases. Among all
      metastatic sites at diagnosis in our subsequently relapsed patient cohort, only 3
      of 19 irradiated sites (15.8%) recurred as compared with 128 of 506 (25.3%)
      unirradiated sites. CONCLUSIONS: Metastatic bone relapse in neuroblastoma usually
      occurs at anatomic sites of previous disease. Metastatic sites identified at
      diagnosis that did not receive radiation during frontline therapy appeared to
      have a higher risk of involvement at first relapse relative to previously
      irradiated metastatic sites. These observations support the current paradigm of
      irradiating metastases that persist after induction chemotherapy in high-risk
      patients. Furthermore, they raise the hypothesis that metastatic sites appearing
      to clear with induction chemotherapy may also benefit from radiotherapeutic
      treatment modalities (external beam radiation or (131)I-MIBG).

PMID- 24867535
TI  - Prone breast intensity modulated radiation therapy: 5-year results.
AB  - PURPOSE: To report the 5-year results of a technique of prone breast radiation
      therapy delivered by a regimen of accelerated intensity modulated radiation
      therapy with a concurrent boost to the tumor bed. METHODS AND MATERIALS: Between
      2003 and 2006, 404 patients with stage I-II breast cancer were prospectively
      enrolled into 2 consecutive protocols, institutional trials 03-30 and 05-181,
      that used the same regimen of 40.5 Gy/15 fractions delivered to the index breast
      over 3 weeks, with a concomitant daily boost to the tumor bed of 0.5 Gy (total
      dose 48 Gy). All patients were treated after segmental mastectomy and had
      negative margins and nodal assessment. Patients were set up prone: only if lung
      or heart volumes were in the field was a supine setup attempted and chosen if
      found to better spare these organs. RESULTS: Ninety-two percent of patients were
      treated prone, 8% supine. Seventy-two percent had stage I, 28% stage II invasive
      breast cancer. In-field lung volume ranged from 0 to 228.27 cm(3), mean 19.65
      cm(3). In-field heart volume for left breast cancer patients ranged from 0 to
      21.24 cm(3), mean 1.59 cm(3). There was no heart in the field for right breast
      cancer patients. At a median follow-up of 5 years, the 5-year cumulative
      incidence of isolated ipsilateral breast tumor recurrence was 0.82% (95%
      confidence interval [CI] 0.65%-1.04%). The 5-year cumulative incidence of
      regional recurrence was 0.53% (95% CI 0.41%-0.69%), and the 5-year overall
      cumulative death rate was 1.28% (95% CI 0.48%-3.38%). Eighty-two percent (95% CI
      77%-85%) of patients judged their final cosmetic result as excellent/good.
      CONCLUSIONS: Prone accelerated intensity modulated radiation therapy with a
      concomitant boost results in excellent local control and optimal sparing of heart
      and lung, with good cosmesis. Radiation Therapy Oncology Group protocol 1005, a
      phase 3, multi-institutional, randomized trial is ongoing and is evaluating the
      equivalence of a similar dose and fractionation approach to standard 6-week
      radiation therapy with a sequential boost.

PMID- 24867536
TI  - Optimal location of radiation therapy centers with respect to geographic access.
AB  - PURPOSE: To develop a framework with which to evaluate locations of radiation
      therapy (RT) centers in a region based on geographic access. METHODS AND
      MATERIALS: Patient records were obtained for all external beam radiation therapy
      started in 2011 for the province of British Columbia, Canada. Two metrics of
      geographic access were defined. The primary analysis was percentage of patients
      (coverage) within a 90-minute drive from an RT center (C90), and the secondary
      analysis was the average drive time (ADT) to an RT center. An integer programming
      model was developed to determine optimal center locations, catchment areas, and
      capacity required under different scenarios. RESULTS: Records consisted of 11,096
      courses of radiation corresponding to 161,616 fractions. Baseline geographic
      access was estimated at 102.5 minutes ADT (each way, per fraction) and 75.9% C90.
      Adding 2 and 3 new centers increased C90 to 88% and 92%, respectively, and
      decreased ADT by between 43% and 61%, respectively. A scenario in which RT was
      provided in every potential location that could support at least 1 fully utilized
      linear accelerator resulted in 35.3 minutes' ADT and 93.6% C90. CONCLUSIONS: The
      proposed framework and model provide a data-driven means to quantitatively
      evaluate alternative configurations of a regional RT system. Results suggest that
      the choice of location for future centers can significantly improve geographic
      access to RT.

PMID- 24867537
TI  - Locoregional control of non-small cell lung cancer in relation to automated early
      assessment of tumor regression on cone beam computed tomography.
AB  - PURPOSE: Large interindividual variations in volume regression of non-small cell
      lung cancer (NSCLC) are observable on standard cone beam computed tomography
      (CBCT) during fractionated radiation therapy. Here, a method for automated
      assessment of tumor volume regression is presented and its potential use in
      response adapted personalized radiation therapy is evaluated empirically. METHODS
      AND MATERIALS: Automated deformable registration with calculation of the Jacobian
      determinant was applied to serial CBCT scans in a series of 99 patients with
      NSCLC. Tumor volume at the end of treatment was estimated on the basis of the
      first one third and two thirds of the scans. The concordance between estimated
      and actual relative volume at the end of radiation therapy was quantified by
      Pearson's correlation coefficient. On the basis of the estimated relative volume,
      the patients were stratified into 2 groups having volume regressions below or
      above the population median value. Kaplan-Meier plots of locoregional disease
      free rate and overall survival in the 2 groups were used to evaluate the
      predictive value of tumor regression during treatment. Cox proportional hazards
      model was used to adjust for other clinical characteristics. RESULTS: Automatic
      measurement of the tumor regression from standard CBCT images was feasible.
      Pearson's correlation coefficient between manual and automatic measurement was
      0.86 in a sample of 9 patients. Most patients experienced tumor volume
      regression, and this could be quantified early into the treatment course.
      Interestingly, patients with pronounced volume regression had worse locoregional
      tumor control and overall survival. This was significant on patient with non
      adenocarcinoma histology. CONCLUSIONS: Evaluation of routinely acquired CBCT
      images during radiation therapy provides biological information on the specific
      tumor. This could potentially form the basis for personalized response adaptive
      therapy.

PMID- 24867538
TI  - Targeting the Renin-angiotensin system combined with an antioxidant is highly
      effective in mitigating radiation-induced lung damage.
AB  - PURPOSE: To investigate the outcome of suppression of the renin angiotensin
      system using captopril combined with an antioxidant (Eukarion [EUK]-207) for
      mitigation of radiation-induced lung damage in rats. METHODS AND MATERIALS: The
      thoracic cavity of female Sprague-Dawley rats was irradiated with a single dose
      of 11 Gy. Treatment with captopril at a dose of 40 mg/kg/d in drinking water and
      EUK-207 given by subcutaneous injection (8 mg/kg daily) was started 1 week after
      irradiation (PI) and continuing until 14 weeks PI. Breathing rate was monitored
      until the rats were killed at 32 weeks PI, when lung fibrosis was assessed by
      lung hydroxyproline content. Lung levels of the cytokine transforming growth
      factor-beta1 and macrophage activation were analyzed by immunohistochemistry.
      Oxidative DNA damage was assessed by 8-hydroxy-2-deoxyguanosine levels, and lipid
      peroxidation was measured by a T-BARS assay. RESULTS: The increase in breathing
      rate in the irradiated rats was significantly reduced by the drug treatments. The
      drug treatment also significantly decreased the hydroxyproline content, 8-hydroxy
      2-deoxyguanosine and malondialdehyde levels, and levels of activated macrophages
      and the cytokine transforming growth factor-beta1 at 32 weeks. Almost complete
      mitigation of these radiation effects was observed by combining captopril and EUK
      207. CONCLUSION: Captopril and EUK-207 can provide mitigation of radiation
      induced lung damage out to at least 32 weeks PI after treatment given 1-14 weeks
      PI. Overall the combination of captopril and EUK-207 was more effective than the
      individual drugs used alone.

PMID- 24867539
TI  - Definitive chemoradiation therapy with docetaxel, cisplatin, and 5-fluorouracil
      (DCF-R) in advanced esophageal cancer: a phase 2 trial (KDOG 0501-P2).
AB  - PURPOSE: A previous phase 1 study suggested that definitive chemoradiation
      therapy with docetaxel, cisplatin, and 5-fluorouracil (DCF-R) is tolerable and
      active in patients with advanced esophageal cancer (AEC). This phase 2 study was
      designed to confirm the efficacy and toxicity of DCF-R in AEC. METHODS AND
      MATERIALS: Patients with previously untreated thoracic AEC who had T4 tumors or
      M1 lymph node metastasis (M1 LYM), or both, received intravenous infusions of
      docetaxel (35 mg/m(2)) and cisplatin (40 mg/m(2)) on day 1 and a continuous
      intravenous infusion of 5-fluorouracil (400 mg/m(2)/day) on days 1 to 5, every 2
      weeks, plus concurrent radiation. The total radiation dose was initially 61.2 Gy
      but was lowered to multiple-field irradiation with 50.4 Gy to decrease
      esophagitis and late toxicity. Consequently, the number of cycles of DCF
      administered during radiation therapy was reduced from 4 to 3. The primary
      endpoint was the clinical complete response (cCR) rate. RESULTS: Characteristics
      of the 42 subjects were: median age, 62 years; performance status, 0 in 14, 1 in
      25, 2 in 3; TNM classification, T4M0 in 20, non-T4M1LYM in 12, T4M1LYM in 10;
      total scheduled radiation dose: 61.2 Gy in 12, 50.4 Gy in 30. The cCR rate was
      52.4% (95% confidence interval [CI]: 37.3%-67.5%) overall, 33.3% in the 61.2-Gy
      group, and 60.0% in the 50.4-Gy group. The median progression-free survival was
      11.1 months, and the median survival was 29.0 months with a survival rate of
      43.9% at 3 years. Grade 3 or higher major toxicity consisted of leukopenia
      (71.4%), neutropenia (57.2%), anemia (16.7%), febrile neutropenia (38.1%),
      anorexia (31.0%), and esophagitis (28.6%). CONCLUSIONS: DCF-R frequently caused
      myelosuppression and esophagitis but was highly active and suggested to be a
      promising regimen in AEC. On the basis of efficacy and safety, a radiation dose
      of 50.4 Gy is recommended for further studies of DCF-R.

PMID- 24867542
TI  - Enantio-relay catalysis constructs chiral biaryl alcohols over cascade Suzuki
      cross-coupling-asymmetric transfer hydrogenation.
AB  - The construction of chiral biaryl alcohols using enantio-relay catalysis is a
      particularly attractive synthetic method in organic synthesis. However,
      overcoming the intrinsic incompatibility of distinct organometallic complexes and
      the reaction conditions used are significant challenges in asymmetric catalysis.
      To overcome these barriers, we have taken advantage of an enantio-relay catalysis
      strategy and a combined dual-immobilization approach. We report the use of an
      imidazolium-based organopalladium-functionalized organic-inorganic hybrid silica
      and ethylene-coated chiral organoruthenium-functionalized magnetic nanoparticles
      to catalyze a cascade Suzuki cross-coupling-asymmetric transfer hydrogenation
      reaction to prepare chiral biaryl alcohols in a two-step, one-pot process. As
      expected, the site-isolated active species, salient imidazolium phase-transfer
      character and high ethylene-coated hydrophobicity can synergistically boost the
      catalytic performance. Furthermore, enantio-relay catalysis has the potential to
      efficiently prepare a variety of chiral biaryl alcohols. Our synthetic strategy
      is a general method that shows the potential of developing enantio-relay
      catalysis towards environmentally benign and sustainable organic synthesis. 

PMID- 24867541
TI  - DOC-2/DAB2 interacting protein status in high-risk prostate cancer correlates
      with outcome for patients treated with radiation therapy.
AB  - PURPOSE: This pilot study investigates the role of DOC-2/DAB2 Interacting Protein
      (DAB2IP) and enhancer of zeste homolog 2 (EZH2) as prognostic biomarkers in high
      risk prostate cancer patients receiving definitive radiation therapy. METHODS AND
      MATERIALS: Immunohistochemistry was performed and scored by an expert
      genitourinary pathologist. Clinical endpoints evaluated were freedom from
      biochemical failure (FFBF), castration resistance-free survival (CRFS), and
      distant metastasis-free survival (DMFS). Log-rank test and Cox regression were
      used to determine significance of biomarker levels with clinical outcome.
      RESULTS: Fifty-four patients with high-risk prostate cancer (stage >= T3a, or
      Gleason score >= 8, or prostate-specific antigen level >= 20 ng/mL) treated with
      radiation therapy from 2005 to 2012 at our institution were evaluated. Nearly all
      patients expressed EZH2 (98%), whereas 28% of patients revealed DAB2IP reduction
      and 72% retained DAB2IP. Median follow-up was 34.0 months for DAB2IP-reduced
      patients, 29.9 months for DAB2IP-retained patients, and 32.6 months in the EZH2
      study. Reduction in DAB2IP portended worse outcome compared with DAB2IP-retained
      patients, including FFBF (4-year: 37% vs 89%, P=.04), CRFS (4-year: 50% vs 90%,
      P=.02), and DMFS (4-year: 36% vs 97%, P=.05). Stratified EZH2 expression trended
      toward significance for worse FFBF and CRFS (P=.07). Patients with reduced DAB2IP
      or highest-intensity EZH2 expression exhibited worse FFBF (4-year: 32% vs 95%,
      P=.02), CRFS (4-year: 28% vs 100%, P<.01), and DMFS (4-year: 39% vs 100%, P=.04)
      compared with the control group. CONCLUSION: Loss of DAB2IP is a potent biomarker
      that portends worse outcome despite definitive radiation therapy for patients
      with high-risk prostate cancer. Enhancer of zeste homolog 2 is expressed in most
      high-risk tumors and is a less potent discriminator of outcome in this study. The
      DAB2IP status in combination with degree of EZH2 expression may be useful for
      determining patients with worse outcome within the high-risk prostate cancer
      population.

PMID- 24867540
TI  - A phase 1/2 and biomarker study of preoperative short course chemoradiation with
      proton beam therapy and capecitabine followed by early surgery for resectable
      pancreatic ductal adenocarcinoma.
AB  - PURPOSE: To evaluate the safety, efficacy and biomarkers of short-course proton
      beam radiation and capecitabine, followed by pancreaticoduodenectomy in a phase
      1/2 study in pancreatic ductal adenocarcinoma (PDAC) patients. METHODS AND
      MATERIALS: Patients with radiographically resectable, biopsy-proven PDAC were
      treated with neoadjuvant short-course (2-week) proton-based radiation with
      capecitabine, followed by surgery and adjuvant gemcitabine. The primary objective
      was to demonstrate a rate of toxicity grade >= 3 of <20%. Exploratory biomarker
      studies were performed using surgical specimen tissues and peripheral blood.
      RESULTS: The phase 2 dose was established at 5 daily doses of 5 GyE. Fifty
      patients were enrolled, of whom 35 patients were treated in the phase 2 portion.
      There were no grade 4 or 5 toxicities, and only 2 of 35 patients (4.1%)
      experienced a grade 3 toxicity event (chest wall pain grade 1, colitis grade 1).
      Of 48 patients eligible for analysis, 37 underwent pancreaticoduodenectomy.
      Thirty of 37 (81%) had positive nodes. Locoregional failure occurred in 6 of 37
      resected patients (16.2%), and distant recurrence occurred in 35 of 48 patients
      (72.9%). With median follow-up of 38 months, the median progression-free survival
      for the entire group was 10 months, and overall survival was 17 months. Biomarker
      studies showed significant associations between worse survival outcomes and the
      KRAS point mutation change from glycine to aspartic acid at position 12, stromal
      CXCR7 expression, and circulating biomarkers CEA, CA19-9, and HGF (all, P<.05).
      CONCLUSIONS: This study met the primary endpoint by showing a rate of 4.1% grade
      3 toxicity for neoadjuvant short-course proton-based chemoradiation. Treatment
      was associated with favorable local control. In exploratory analyses, KRAS(G12D)
      status and high CXCR7 expression and circulating CEA, CA19-9, and HGF levels were
      associated with poor survival.

PMID- 24867544
TI  - Introducing healing circles and talking circles into primary care.
AB  - We report on the incorporation of a North American aboriginal procedure called
      "the talking circle" into primary care in areas serving this population.
      Communication is regulated through the passing of a talking piece (an object of
      special meaning or symbolism to the circle facilitator, who is usually called the
      circle keeper). Twelve hundred people participated in talking circles in which
      415 attended 4 sessions and completed pre- and postquestionnaires. Outcome
      measures included baseline and end Measure Your Medical Outcome Profile version 2
      forms. Participation in at least 4 talking circles resulted in a statistically
      significant improvement in reported symptoms and overall quality of life (p <
      0.001 and effect sizes ranging from 0.75 to 1.19). The talking circle is a useful
      tool to use with Native Americans. It may be useful as a means to reduce health
      care costs by providing other alternative settings to deal with stress-related
      and other life problems.

PMID- 24867543
TI  - Multiscale patterning of a biomimetic scaffold integrated with composite
      microspheres.
AB  - The ideal scaffold for regenerative medicine should concurrently mimic the
      structure of the original tissue from the nano- up to the macroscale and
      recapitulate the biochemical composition of the extracellular matrix (ECM) in
      space and time. In this study, a multiscale approach is followed to selectively
      integrate different types of nanostructured composite microspheres loaded with
      reporter proteins, in a multi-compartment collagen scaffold. Through the
      preservation of the structural cues of the functionalized collagen scaffold at
      the nano- and microscale, its macroscopic features (pore size, porosity, and
      swelling) are not altered. Additionally, the spatial confinement of the
      microspheres allows the release of the reporter proteins in each of the layers of
      the scaffold. Finally, the staged and zero-order release kinetics enables the
      temporal biochemical patterning of the scaffold. The versatile manufacturing of
      each component of the scaffold results in the ability to customize it to better
      mimic the architecture and composition of the tissues and biological systems. 

PMID- 24867545
TI  - Using simulation to address hierarchy-related errors in medical practice.
AB  - OBJECTIVE: Hierarchy, the unavoidable authority gradients that exist within and
      between clinical disciplines, can lead to significant patient harm in high-risk
      situations if not mitigated. High-fidelity simulation is a powerful means of
      addressing this issue in a reproducible manner, but participant psychological
      safety must be assured. Our institution experienced a hierarchy-related
      medication error that we subsequently addressed using simulation. The purpose of
      this article is to discuss the implementation and outcome of these simulations.
      METHODS: Script and simulation flowcharts were developed to replicate the case.
      Each session included the use of faculty misdirection to precipitate the error.
      Care was taken to assure psychological safety via carefully conducted briefing
      and debriefing periods. Case outcomes were assessed using the validated Team
      Performance During Simulated Crises Instrument. Gap analysis was used to quantify
      team self-insight. Session content was analyzed via video review. RESULTS: Five
      sessions were conducted (3 in the pediatric intensive care unit and 2 in the
      Pediatric Emergency Department). The team was unsuccessful at addressing the
      error in 4 (80%) of 5 cases. Trends toward lower communication scores (3.4/5 vs
      2.3/5), as well as poor team self-assessment of communicative ability, were noted
      in unsuccessful sessions. Learners had a positive impression of the case.
      CONCLUSIONS: Simulation is a useful means to replicate hierarchy error in an
      educational environment. This methodology was viewed positively by learner teams,
      suggesting that psychological safety was maintained. Teams that did not address
      the error successfully may have impaired self-assessment ability in the
      communication skill domain.

PMID- 24867546
TI  - Online cognitive behavioral therapy for depressed primary care patients: a pilot
      feasibility project.
AB  - CONTEXT: Cognitive behavioral therapy (CBT) is a goal-oriented treatment that
      guides patients to healthy thoughts and behaviors. Internet-delivered CBT with
      supportive coaching can be as effective as in-person psychotherapy treatment of
      depression. OBJECTIVE: To test the feasibility of engaging depressed primary care
      patients not currently receiving psychotherapy and to measure the outcomes of
      Internet-delivered CBT with supportive coaching. DESIGN: Pilot feasibility
      project. MAIN OUTCOME MEASURES: 1) Uptake rate. 2) Reduction in depressive
      symptoms (average score on 20-item Hopkins Symptom Checklist) from baseline to 4
      month follow-up. METHODS: Medical records data were queried to identify patients
      experiencing a new episode of depression. Eligible patients were invited via
      secure messaging (patient and clinician communication using a secure Web site
      linked to the medical record) to participate in the Internet-delivered CBT
      program (also known as Thrive), which was algorithm-driven and delivered through
      didactic segments, interactive tools, and assessments. Patients completed a self
      administered online follow-up survey four months after enrollment. RESULTS: Of
      196 eligible patients who were sent an invitation, 39 (20%) enrolled in the
      Internet-delivered CBT program. At follow-up, enrolled patients experienced a
      clinically significant decrease (average = 46%) in depressive symptoms. Suicidal
      thoughts also decreased both overall and by severity. CONCLUSIONS: Seamless,
      scalable integration of Internet-delivered CBT into health care systems is
      feasible. The 20% uptake rate suggests that future work should focus on
      strategies to increase the initial response rate. One promising direction is the
      addition of "human touch" to the secure message invitation. Depression outcomes
      suggest promise for systemwide implementation of Internet-delivered CBT programs.

PMID- 24867547
TI  - Use of a modified reproductive life plan to improve awareness of preconception
      health in women with chronic disease.
AB  - OBJECTIVE: Chronic diseases such as hypertension, diabetes, and obesity pose
      unique reproductive challenges for women. Preconception health results in
      improved reproductive outcomes. We designed an interventional study testing the
      use of a reproductive life plan to improve knowledge of preconception and
      contraception health in women with chronic diseases. METHODS: Primarily
      underserved, English-and Spanish-speaking women aged 18 to 40 years with active
      diabetes, hypertension, or obesity were recruited. We developed a revised
      reproductive life plan specific to these diseases. Two resident physicians
      performed reproductive plan counseling. Pre- and postcounseling surveys were
      administered to evaluate knowledge and attitudes about chronic disease and the
      effects on a potential pregnancy. RESULTS: Twenty-seven women (average age = 31
      years) were surveyed. Of the subjects, 85.2% were obese, 29.6% had hypertension,
      and 7.4% had diabetes. Significant increases were reported in understanding risks
      of pregnancy associated with diabetes (p < 0.001), hypertension (p < 0.001), and
      obesity (p < 0.01). After counseling, women increased their knowledge about a
      reproductive plan (p < 0.001) and increased support and information to make
      reproductive health choices (p = 0.001 and p < 0.01, respectively). The largest
      improvements in postcounseling variables occurred in women with the lowest
      precounseling test scores and in women without children. CONCLUSION: A
      reproductive life plan is a brief, cost-effective preconception and contraception
      counseling tool in the primary care setting for women with chronic diseases. This
      tool increases knowledge about reproductive health and enables women with chronic
      diseases to make informed decisions about their reproductive future.

PMID- 24867548
TI  - Toward a trustworthy voice: increasing the effectiveness of automated outreach
      calls to promote colorectal cancer screening among African Americans.
AB  - INTRODUCTION: Colorectal cancer screening rates are lower among African-American
      members of Kaiser Permanente Colorado (KPCO) than among members of other races
      and ethnicities. This study evaluated use of a linguistically congruent voice in
      interactive voice response outreach calls about colorectal cancer screening as a
      strategy to increase call completion and response. METHODS: After an initial
      discussion group to assess cultural acceptability of the project, 6 focus groups
      were conducted with 33 KPCO African-American members. Participants heard and
      discussed recordings of 5 female voices reading the same segment of the standard
      practice colorectal cancer message using interactive voice response. The
      linguistic palette included the voices of a white woman, a lightly accented
      Latina, and 3 African-American women. RESULTS: Participants strongly preferred
      the African-American voices, particularly two voices. Participants considered
      these voices the most trustworthy and reported that they would be the most
      effective at increasing motivation to complete an automated call. Participants
      supported the use of African-American voices when designing outgoing automated
      calls for African Americans because the sense of familiarity engendered trust
      among listeners. Participants also indicated that effective automated messages
      should provide immediate clarity of purpose; explain why the issue is relevant to
      African Americans; avoid sounding scripted; emphasize that the call is for the
      listener's benefit only; sound personable, warm, and positive; and not create
      fear among listeners. DISCUSSION: Establishing linguistic congruence between
      African Americans and the voices used in automated calls designed to reach them
      may increase the effectiveness of outreach efforts.

PMID- 24867549
TI  - Prospects and problems of transferring quality-improvement methods from health
      care to social services: two case studies.
AB  - INTRODUCTION: This study examines the use of quality-improvement (QI) methods in
      social services. Particularly the key aspects-generalizable knowledge,
      interprofessional teamwork, and measurements-are studied in projects from the QI
      program Forum for Values in Sweden. METHODS: This is a mixed-method case study.
      Two projects using standard QI methods and tools as used in health care were
      chosen as critical cases to highlight some problems and prospects with the use of
      QI in social services. The cases were analyzed through documented results and
      qualitative interviews with participants one year after the QI projects ended.
      RESULTS: The social service QI projects led to measurable improvements when they
      used standard methods and tools for QI in health care. One year after the
      projects, the improvements were either not continuously measured or not reported
      in any infrastructure for measurements. The study reveals that social services
      differ from health care regarding the availability and use of evidence, the role
      of professional expertise, and infrastructure for measurements. CONCLUSIONS: We
      argue that QI methods as used in health care are applicable in social services
      and can lead to measurable improvements. The study gives valuable insights for
      QI, not only in social services but also in health care, on how to assess and
      sustain improvements when infrastructures for measurements are lacking. In
      addition, when one forms QI teams, the focus should be on functions instead of
      professions, and QI methods can be used to support implementation of evidence
      based practice.

PMID- 24867550
TI  - RISQy business (Relationships, Incentives, Supports, and Quality): evolution of
      the British Columbia Model of Primary Care (patient-centered medical home).
AB  - In 2002, the British Columbia Ministry of Health and the British Columbia Medical
      Association (now Doctors of BC) came together to form the British Columbia
      General Practice Services Committee to bring about transformative change in
      primary care in British Columbia, Canada. This committee's approach to primary
      care was to respond to an operational problem--the decline of family practice in
      British Columbia--with an operational solution--assist general practitioners to
      provide better care by introducing new incentive fees into the fee-for-service
      payment schedule, and by providing additional training to general practitioners.
      This may be referred to as a "soft power" approach, which can be summarized in
      the abbreviation RISQ: focus on Relationships; provide Incentives for general
      practitioners to spend more time with their patients and provide guidelines-based
      care; Support general practitioners by developing learning modules to improve
      their practices; and, through the incentive payments and learning modules,
      provide better Quality care to patients and improved satisfaction to physicians.
      There are many similarities between the British Columbian approach to primary
      care and the US patient-centered medical home.

PMID- 24867552
TI  - Medical missions-overrated or undervalued? A single program experience.

PMID- 24867551
TI  - Creating a longitudinal integrated clerkship with mutual benefits for an academic
      medical center and a community health system.
AB  - The longitudinal integrated clerkship is a model of clinical education driven by
      tenets of social cognitive theory, situated learning, and workplace learning
      theories, and built on a foundation of continuity between students, patients,
      clinicians, and a system of care. Principles and goals of this type of clerkship
      are aligned with primary care principles, including patient-centered care and
      systems-based practice. Academic medical centers can partner with community
      health systems around a longitudinal integrated clerkship to provide mutual
      benefits for both organizations, creating a sustainable model of clinical
      training that addresses medical education and community health needs. A
      successful one-year longitudinal integrated clerkship was created in partnership
      between an academic medical center and an integrated community health system.
      Compared with traditional clerkship students, students in this clerkship had
      better scores on Clinical Performance Examinations, internal medicine
      examinations, and high perceptions of direct observation of clinical
      skills.Advantages for the academic medical center include mitigating the
      resources required to run a longitudinal integrated clerkship while providing
      primary care training and addressing core competencies such as systems-based
      practice, practice-based learning, and interprofessional care. Advantages for the
      community health system include faculty development, academic appointments,
      professional satisfaction, and recruitment.Success factors include continued
      support and investment from both organizations' leadership, high-quality faculty
      development, incentives for community-based physician educators, and emphasis on
      the mutually beneficial relationship for both organizations. Development of a
      longitudinal integrated clerkship in a community health system can serve as a
      model for developing and expanding these clerkship options for academic medical
      centers.

PMID- 24867553
TI  - The coccidioidomycosis conundrum: a rare parotid mass.
AB  - A man, age 62 years, presented to the clinic with a 2-week history of increased
      nontender, nonerythematous, indurated right-sided parotid swelling. A 4 * 6-cm
      firm, well-circumscribed mass was palpated in the right parotid gland. A fine
      needle aspiration biopsy was performed on the parotid mass with aspiration of 0.5
      cc of purulent fluid with some blood. Cultures from the aspirate revealed
      Coccidioides immitis confirmed by DNA probe. Pathology slides revealed fungal
      spores. The patient was treated with 800 mg of fluconazole every day for 3 months
      with resolution of the parotid swelling. However, persistent cervical adenopathy
      remains.Although this is a rare case of acute parotid swelling, Coccidioides
      immitis should be considered in the differential diagnosis of parotid masses in a
      patient with previous coccidioidomycosis. There may be a potential for an
      increase in frequency and variety of atypical extrapulmonary manifestations of
      coccidioidomycosis that parallels the increase in coccidioidomycotic pulmonary
      infections. Long-term antifungal therapy appears essential for control.

PMID- 24867554
TI  - What can we learn from narratives in medical education?
AB  - Medical literature has demonstrated the effectiveness of narrative writing in
      enhancing self-reflection and empathy, which opens the door for deeper
      understanding of patients' experiences of illness. Similarly, it promotes
      practitioner well-being. Therefore, it is no surprise that narrative writing
      finds a new home in medical education. The Accreditation Council of Graduate
      Medical Education (ACGME), through its Outcome Project, established six core
      competencies that every residency program must teach. However, no specific
      pedagogies were suggested. We explored the role that narrative writing can play
      in reconciling the ACGME core competencies with daily encounters in medical
      education. Our study suggests a hidden wealth in reflective writing through
      narratives with a promising potential for application in medical education.
      Reflective writing may turn out to be an innovative tool for teaching and
      evaluating ACGME core competencies.

PMID- 24867555
TI  - ECG diagnosis: Type I atrial flutter.

PMID- 24867557
TI  - Image diagnosis: Medullary sponge kidney.

PMID- 24867558
TI  - Image diagnosis: Sister Mary Joseph nodule.

PMID- 24867559
TI  - ECG diagnosis: ST-elevation myocardial infarction.

PMID- 24867561
TI  - Improving alcohol withdrawal outcomes in acute care.
AB  - CONTEXT: Excessive alcohol consumption is the nation's third leading cause of
      preventable deaths. If untreated, 6% of alcohol-dependent patients experience
      alcohol withdrawal, with up to 10% of those experiencing delirium tremens (DT),
      when they stop drinking. Without routine screening, patients often experience DT
      without warning. OBJECTIVE: Reduce the incidence of alcohol withdrawal advancing
      to DT, restraint use, and transfers to the intensive care unit (ICU) in patients
      with DT. DESIGN: In October 2009, the alcohol withdrawal team instituted a care
      management guideline used by all disciplines, which included tools for screening,
      assessment, and symptom management. Data were obtained from existing datasets for
      three quarters before and four quarters after implementation. Follow-up data were
      analyzed and showed a great deal of variability in transfers to the ICU and
      restraint use. Percentage of patients who developed DT showed a downward trend.
      MAIN OUTCOME MEASURES: Incidence of alcohol withdrawal advancing to DT and, in
      patients with DT, restraint use and transfers to the ICU. RESULTS: Initial data
      revealed a decrease in percentage of patients with alcohol withdrawal who
      experienced DT (16.4%-12.9%). In patients with DT, restraint use decreased (60.4%
      44.4%) and transfers to the ICU decreased (21.6%-15%). Follow-up data indicated a
      continued downward trend in patients with DT. Changes were not statistically
      significant. Restraint use and ICU transfers maintained postimplementation levels
      initially but returned to preimplementation levels by third quarter 2012.
      CONCLUSION: Early identification of patients for potential alcohol withdrawal
      followed by a standardized treatment protocol using symptom-triggered dosing
      improved alcohol withdrawal management and outcomes.

PMID- 24867560
TI  - Nurse practitioner management of type 2 diabetes.
AB  - CONTEXT: Multifactorial barriers prevent primary care clinicians from helping
      their adult patients with type 2 diabetes achieve good control of hemoglobin A1c
      (HbA1c) levels. Patients' depression and low self-efficacy can complicate
      diabetes management by impairing tasks needed for effective disease self
      management. OBJECTIVES: To evaluate whether nurse practitioners in collaborative
      practices with primary care clinicians are effective in helping improve control
      of HbA1c, blood pressure (BP), and low-density lipoprotein cholesterol (LDL-C) in
      adults with uncontrolled hyperglycemia, and to assess whether nurse practitioner
      guided care affects depression and self-efficacy in these patients. DESIGN: De
      identified preintervention and postintervention data were collected from
      prospective review of medical charts of patients in a managed care organization's
      primary care clinics. MAIN OUTCOME MEASURES: Preintervention and postintervention
      HbA1c values were evaluated as the primary outcome measure. Preintervention and
      postintervention values for BP, LDL-C, body weight, and depression and self
      efficacy scores were secondary outcome measures. RESULTS: After intervention, 50%
      of 26 patients achieved HbA1c benchmarks, 95.6% achieved systolic and diastolic
      BP benchmarks, and 57.8% achieved LDL-C benchmarks. Wilcoxon paired samples tests
      showed significantly increased self-efficacy (z = -3.42, p < 0.001) from
      preintervention to postintervention. Depression scores decreased slightly from
      preintervention (mean = 0.44, standard deviation = 1.34, median < 0.001) to
      postintervention values (mean = 0.18, standard deviation = 0.73, median < 0.001),
      but this decrease was not significant. CONCLUSION: Integrating nurse
      practitioners into primary care teams to provide innovative methods of support to
      adults with uncontrolled hyperglycemia improves clinical outcomes and self
      efficacy for patients with type 2 diabetes.

PMID- 24867563
TI  - Prevalence of alcohol and drugs among car and van drivers killed in road
      accidents in Norway: an overview from 2001 to 2010.
AB  - OBJECTIVES: To examine the prevalence of alcohol and drugs in blood samples
      collected from car and van drivers killed in traffic accidents in Norway during
      the time period from 2001 to 2010. METHODS: Blood samples (n = 676, 63% of all
      killed drivers) were analyzed for alcohol, psychoactive medications, and illicit
      drugs. The cutoff limits for positive results were set according to the new
      legislative limits under the Norwegian Road Traffic Act. The results were
      assessed in relation to sex and age, time of day and day of week, and single-
      versus multiple-vehicle and all investigated vehicle accidents. RESULTS: Alcohol
      or one or more drugs was detected in samples from 40.2 percent of all
      investigated drivers, with 28.7 percent showing blood concentrations of at least
      5 times the legislative limits. For the investigated female drivers, the total
      prevalence was 24.0 percent. Among the single-vehicle accidents, alcohol or drugs
      was found in 63.8 percent of the cases, with 49.1 percent showing blood
      concentrations of at least 5 times the legislative limits. Alcohol was detected
      in 25.3 and 49.1 percent of samples from all investigated drivers and among
      drivers killed in single-vehicle accidents, respectively. Psychoactive
      medications were found in 14.4 and 17.7 percent and illicit drugs in 14.1 and
      19.2 percent, respectively. The most commonly detected group of medications was
      benzodiazepines, and amphetamines and tetrahydrocannabinol were the most commonly
      detected illicit drugs. The prevalence of alcohol alone was highest among drivers
      under the age of 25, and the combination of alcohol with other drugs was highest
      among drivers under the age of 35. Drivers between the ages of 25 and 54 showed
      the highest prevalence of medications and/or illicit drugs without the presence
      of alcohol. The highest prevalence of alcohol or drugs was found among drivers
      killed in single-vehicle accidents on weeknights (83.8%) and on weekend nights
      (89.3%). CONCLUSIONS: The findings confirm that a large number of fatally injured
      drivers, in particular among drivers involved in single-vehicle accidents, had
      concentrations of alcohol or drugs above the new legislative limits introduced in
      2012. In many cases, concentrations of at least 5 times the limits were found.
      The proportion of drivers killed who tested positive for alcohol or other drugs
      did not change during the study period; however, the total number of drivers
      killed per year decreased by about 20 percent. Some changes were also observed
      with regard to the types of benzodiazepines and amphetamines detected during the
      10-year period.

PMID- 24867564
TI  - Characteristics of 1226 alcohol-positive drivers involved in nonfatal traffic
      crashes in Shanghai, China.
AB  - OBJECTIVE: The purpose of our study was to better characterize and evaluate drunk
      driving for governmental reference in order to further reduce alcohol-impaired
      driving. METHOD: This article reports the characteristics of 1226 alcohol
      positive drivers with blood alcohol concentrations (BACs) at or over the legal
      limit of 0.20 mg/mL involved in nonfatal traffic accidents in Shanghai, China,
      from 2008 to 2011. The mean BAC, age, and gender of these drivers are discussed
      as well as the vehicle types and times of day when the crashes occurred. RESULTS:
      The mean BAC was 1.41 mg/mL and the mean age was 38 years old, and the vast
      majority of drivers were male (96.9%). The mean BAC of male drivers (1.42 mg/mL)
      was higher than that of female drivers (1.20 mg/mL). The mean age of male drivers
      (38) was also higher than that of female drivers (33). Distributions of vehicle
      types involved were studied. Cars had the highest percentage of occurrences
      (56.4%), followed by motorcycles (32.8%), electric bicycles (6.8%), trucks
      (1.5%), and bicycles (0.8%). It was found that these alcohol-related traffic
      crashes most often occurred between 7:00 p.m. and 10:59 p.m., representing 48.1
      percent (n = 590) of the 1226 cases. Single-vehicle crashes were overrepresented
      (70.3%) in all cases. The mean BAC in multivehicle crashes (1.69 mg/mL) was
      higher than that in single-vehicle crashes (1.30 mg/mL). CONCLUSIONS: The results
      indicated a notable need for more governmental attention that would prevent
      accidents caused by driving under the influence of alcohol.

PMID- 24867565
TI  - Phone use while driving: results from an observational survey.
AB  - OBJECTIVES: The aim of this study was to quantify the level of handheld phone use
      when driving in South Australia. The study also sought to investigate any driver,
      site, and vehicle characteristics associated with handheld phone use to inform
      countermeasure development and publicity campaigns. METHOD: An on-road
      observational survey of handheld phone use was undertaken as part of a larger
      restraint use survey. The survey was conducted at 61 sites in metropolitan
      Adelaide and rural regions within South Australia on weekdays and a weekend in
      2009. RESULTS: A total of 64 (0.6%) of the 11,524 drivers observed during the
      survey were using handheld phones. Handheld phone usage rates ranged from 0.8
      percent in metropolitan Adelaide to 0.3 percent in the rural region of The
      Riverland. Of all driver, site, and vehicle characteristics examined, the only
      statistically significant difference in handheld phone usage was for the number
      of vehicle occupants. The odds of a driver using a handheld phone while traveling
      alone was over 4 times higher than for a driver traveling with passengers.
      CONCLUSIONS: The level of handheld phone use among drivers in South Australia
      appears to be low relative to other jurisdictions. The level of enforcement
      activity and severity of penalties do not offer a clear explanation for the
      higher levels of compliance with phone laws. Given the rate of increase in phone
      technology, it is important to conduct regular roadside surveys of phone use
      among drivers to monitor trends in usage over time.

PMID- 24867566
TI  - The effectiveness of red light cameras in the United States-a literature review.
AB  - OBJECTIVE: To examine the available scientific evidence based on peer-reviewed
      publications concerning the effectiveness of red light cameras (RLCs) within the
      U.S. traffic system. METHODS: Relevant literature published prior to December
      2012 was retrieved from the PubMed, Medline, and Engineering Index databases
      using free-text term queries. Jurisdictions with either a fixed number of RLCs
      studied or area wide programs within the United States were included. RLC studies
      with additional interventions were excluded. Nine RLC studies were extracted and
      grouped into 3 categories based on outcome measures: violations, crashes, and
      injuries/fatalities. RESULTS: All 9 studies reviewed showed significant
      reductions in the frequency/rate of violations, crashes, and injuries at
      intersections after RLC implementation. RLC interventions appear to decrease
      violations, crashes, and injuries at intersections. CONCLUSIONS: Despite limited
      peer-reviewed publications available in the literature, it appears that RLCs
      decrease violations, crashes, and injuries at intersections. Some studies,
      however, contained methodological shortcomings. Therefore, the apparent
      effectiveness should be confirmed with stronger methodological approaches.
      Although spillover effects appeared to be evident, many of the jurisdictions
      examined were small in area. Thus, it is unknown whether spillover resulting from
      RLCs would have similar effects in large metropolitan areas. To determine the
      full public health impact of RLC programs, crashes, injuries, and fatalities
      should be considered as primary outcomes of interest. To accomplish this requires
      a clear definition of which types of crashes will be included for RLC studies.
      Lastly, it is unknown whether RLCs would be effective in reducing crashes
      resulting from distracted or alcohol-impaired drivers. Future studies should
      examine the effects of RLCs by exclusively analyzing these crash types.

PMID- 24867567
TI  - Optimizing the passenger air bag of an adaptive restraint system for multiple
      size occupants.
AB  - OBJECTIVE: The development of the adaptive occupant restraint system (AORS) has
      led to an innovative way to optimize such systems for multiple size occupants. An
      AORS consists of multiple units such as adaptive air bags, seat belts, etc.
      During a collision, as a supplemental protective device, air bags can provide
      constraint force and play a role in dissipating the crash energy of the
      occupants' head and thorax. This article presents an investigation into an
      adaptive passenger air bag (PAB). METHODS: The purpose of this study is to
      develop a base shape of a PAB for different size occupants using an optimization
      method. Four typical base shapes of a PAB were designed based on geometric data
      on the passenger side. Then 4 PAB finite element (FE) models and a validated sled
      with different size dummy models were developed in MADYMO (TNO, Rijswijk, The
      Netherlands) to conduct the optimization to obtain the best baseline PAB that
      would be used in the AORS. The objective functions-that is, the minimum total
      probability of injuries (?Pcomb) of the 5th percentile female and 50th and 95th
      percentile male dummies-were adopted to evaluate the optimal configurations. The
      injury probability (Pcomb) for each dummy was adopted from the U.S. New Car
      Assessment Program (US-NCAP). RESULTS: The parameters of the AORS were first
      optimized for different types of PAB base shapes in a frontal impact. Then,
      contact time duration and force between the PAB and dummy head/chest were
      optimized by adjusting the parameters of the PAB, such as the number and position
      of tethers, lower the Pcomb of the 95th percentile male dummy. CONCLUSIONS:
      According to the optimization results, 4 typical PABs could provide effective
      protection to 5th and 50th percentile dummies. However, due to the heavy and
      large torsos of the 95th percentile occupants, the current occupant restraint
      system does not demonstrate satisfactory protective function, particularly for
      the thorax.

PMID- 24867569
TI  - Demonstrating a correlation between the maturity of road safety practices and
      road safety incidents.
AB  - OBJECTIVE: The objective of this study is to demonstrate a correlation between
      the maturity of a country's road safety practices and road safety incidents.
      METHODS: Firstly, data on a number of road injuries and fatalities for 129
      countries were extracted from the United Nations Global Status on Road Safety
      database. These data were subdivided according to road safety incident and
      accident causation factors and normalized based on vehicular fleet (per 1000
      vehicles) and road network (per meter of paved road). Secondly, a road safety
      maturity model was developed based on an adaptation of the concept of process
      maturity modeling. The maturity of countries with respect to 10 road safety
      practices was determined through the identification of indicators recorded in the
      United Nations Global Status of Road Safety Database. Plots of normalized road
      safety performance of the 129 countries against their maturity scores for each
      road safety practice as well as an aggregation of the road safety practices were
      developed. An analysis of variance was done to determine the extent of the
      correlation between the road safety maturity of the countries and their
      performance. In addition, a full Bayesian analysis was done to confirm the
      correlation of each of the road safety practices with injuries and fatalities.
      RESULTS: Regression analysis for fatalities, injuries, and combined accidents
      identified maturity with respect to road safety practices associated with speed
      limits and use of alternative modes as being the most significant predictors of
      traffic fatalities. A full Bayesian regression confirms that there is a
      correlation between the maturity of road safety practices and road safety
      incidents. CONCLUSION: Road safety practices associated with enforcement of speed
      limits and promotion of alternative modes are the most significant road safety
      practices toward which mature countries have concentrated their efforts,
      resulting in a lower frequency of fatalities, injury rates, and property damage
      accidents. The authors argue that the use of gross domestic product (GDP) as a
      predictor of road safety incidents suffers from the presumptive assumption that
      the only criterion that matters is national income, therefore erroneously
      predicting that richer countries all perform approximately the same in fatalities
      and that developing nations are at various stages, with high variability and
      uncertainty in prediction. It is proposed that an aggregation of individual
      maturity scores from road safety practices will lead to a better indicator for
      policy because it connects externalities (fatalities/injuries) with intrinsic
      factors for which policies can be oriented.

PMID- 24867568
TI  - Estimating rear-end accident probabilities at signalized intersections: a
      comparison study of intersections with and without green signal countdown
      devices.
AB  - OBJECTIVE: Rear-end accidents are the most common accident type at signalized
      intersections, because the diversity of actions taken increases due to signal
      change. Green signal countdown devices (GSCDs), which have been widely installed
      in Asia, are thought to have the potential of improving capacity and reducing
      accidents, but some negative effects on intersection safety have been observed in
      practice; for example, an increase in rear-end accidents. METHODS: A microscopic
      modeling approach was applied to estimate rear-end accident probability during
      the phase transition interval in the study. The rear-end accident probability is
      determined by the following probabilities: (1) a leading vehicle makes a "stop"
      decision, which was formulated by using a binary logistic model, and (2) the
      following vehicle fails to stop in the available stopping distance, which is
      closely related to the critical deceleration used by the leading vehicle. Based
      on the field observation carried out at 2 GSCD intersections and 2 NGSCD
      intersections (i.e., intersections without GSCD devices) along an arterial in
      Suzhou, the rear-end probabilities at GSCD and NGSCD intersections were
      calculated using Monte Carlo simulation. RESULTS: The results suggested that, on
      the one hand, GSCDs caused significantly negative safety effects during the
      flashing green interval, especially for vehicles in a zone ranging from 15 to 70
      m; on the other hand, GSCD devices were helpful in reducing rear-end accidents
      during the yellow interval, especially in a zone from 0 to 50 m. CONCLUSIONS:
      GSCDs helped shorten indecision zones and reduce rear-end collisions near the
      stop line during the yellow interval, but they easily resulted in risky car
      following behavior and much higher rear-end collision probabilities at indecision
      zones during both flashing green and yellow intervals. GSCDs are recommended to
      be cautiously installed and education on safe driving behavior should be
      available.

PMID- 24867570
TI  - Road safety forecasts in five European countries using structural time series
      models.
AB  - OBJECTIVE: Modeling road safety development is a complex task and needs to
      consider both the quantifiable impact of specific parameters as well as the
      underlying trends that cannot always be measured or observed. The objective of
      this research is to apply structural time series models for obtaining reliable
      medium- to long-term forecasts of road traffic fatality risk using data from 5
      countries with different characteristics from all over Europe (Cyprus, Greece,
      Hungary, Norway, and Switzerland). METHODS: Two structural time series models are
      considered: (1) the local linear trend model and the (2) latent risk time series
      model. Furthermore, a structured decision tree for the selection of the
      applicable model for each situation (developed within the Road Safety Data,
      Collection, Transfer and Analysis [DaCoTA] research project, cofunded by the
      European Commission) is outlined. First, the fatality and exposure data that are
      used for the development of the models are presented and explored. Then, the
      modeling process is presented, including the model selection process,
      introduction of intervention variables, and development of mobility scenarios.
      RESULTS: The forecasts using the developed models appear to be realistic and
      within acceptable confidence intervals. The proposed methodology is proved to be
      very efficient for handling different cases of data availability and quality,
      providing an appropriate alternative from the family of structural time series
      models in each country. CONCLUSIONS: A concluding section providing perspectives
      and directions for future research is presented.

PMID- 24867571
TI  - A one year pay-as-you-speed trial with economic incentives for not speeding.
AB  - OBJECTIVE: The objective was to identify whether it was possible to change driver
      behavior by economic incentives and thereby reduce crash risk. Furthermore, the
      objective was to evaluate the participants' attitudes toward the pay-as-you-speed
      (PAYS) concept. METHODS: A one-year PAYS trial with economic incentives for
      keeping speed limits using intelligent speed assistance (ISA) was conducted in
      Sweden during 2011-2012. The full incentive was a 30 percent discount off the
      insurance premium. The participants were private insurance customers and were
      randomized into a test group (initial n = 152, final n = 128) and a control group
      (initial n = 98, final n = 68). When driving, the drivers in the test group were
      informed and warned visually when the speed limit was exceeded. They could also
      follow their driving results on a personal website. The control group was not
      given any feedback at all. To reflect the impact of the PAYS concept the
      proportion of distance driven above the speed limit was compared between the 2
      groups. RESULTS: The introduction of a PAYS concept shows that the test group
      significantly reduced the proportion of distance driven above the speed limit.
      The proportion of driving at a speed exceeding 5 km/h over the speed limit was 6
      percent for the test group and 14 percent for the control group. It also showed
      that the effect was higher the higher the violation of speed. The result remained
      constant over time. CONCLUSIONS: It was shown that a PAYS concept is an effective
      way to reduce speed violations. Hence, it has the possibility to reduce crash
      severity and thereby to save lives. This could be an important step toward a
      safer road transport system. The majority of the participants were in favor of
      the concept, which indicates the potential of a new insurance product in the
      future.

PMID- 24867572
TI  - Can anatomical morphomic variables help predict abdominal injury rates in frontal
      vehicle crashes?
AB  - OBJECTIVE: Abdominal injuries resulting from vehicle crashes can be significant,
      in particular when undetected. In this study, abdominal injuries for occupants
      involved in frontal impacts were assessed using crash and medical data. METHODS:
      Injury rates and patterns were first assessed with respect to thoracic injuries.
      A statistical analysis was then conducted to predict abdominal injury outcome
      using 18 covariate variables, including 4 vehicle, 4 demographic, and 10
      morphomic, derived from computed tomography (CT) scans. More than 260,000
      logistic regression models were fitted using all possible variable combinations.
      The models were ranked using the Akaike information criterion (AIC) and combined
      through the model-averaging approach to produce the optimal predictive model. The
      performance of the models was then assessed using the area under the curve (AUC).
      RESULTS: The rate of serious thoracic injury was 2.49 times higher than the rate
      of abdominal injury. The associated odds ratio was 2.31 (P <.01). These results
      suggest a strong association between serious abdominal and thoracic injuries. The
      optimal model AUC was 0.646 when using solely vehicle data, 0.696 when combining
      vehicle and demographic data, 0.866 when combining vehicle and morphomic data,
      and 0.879 when combining vehicle, demographic, and morphomic data. These results
      suggest that morphomic variables better predict abdominal injury outcomes than
      demographic variables. The most important morphomics variables included visceral
      fat area, trabecular bone density, and spine angulation. CONCLUSION: This study
      is the first to combine vehicle, demographic, and anatomical data to predict
      abdominal injury rates in frontal crashes.

PMID- 24867573
TI  - Raised crosswalks on entrance to the roundabout-a case study on effectiveness of
      treatment on pedestrian safety and convenience.
AB  - OBJECTIVE: A common concern in the use of a roundabout is providing adequately
      for the pedestrian. This unique roundabout layout, which introduces raised
      crosswalks directly at the roundabout entrance, as opposed to at a car length
      back, aims at improving safety and convenience for pedestrians at roundabouts.
      METHODS: A preliminary evaluation of the layout was undertaken to establish its
      effectiveness in meeting study objectives. A quasi-experimental before-and-after
      study design was used to compare speeds on approach and immediately prior to the
      crossing to ascertain potential impact speed and implications for pedestrian
      safety. Compliance to crossing and crossing time were also compared in relation
      to safety and convenience outcomes. A questionnaire assessed pedestrian
      perception of the safety and convenience at the roundabout before and after
      treatment. RESULTS: Results from this case study indicate that mean approach
      speeds (free speeds 30 m from crossing) reduced from 32.7 to 30.7 km/h and
      immediately prior to crossing, mean speeds reduced from 19.1 to 16.3 km/h. There
      was also a marked reduction in proportions of vehicles traveling at speeds that
      could elevate risk to pedestrians. Total crossing time after treatment reduced by
      around 4 s, and crossing compliance increased from approximately half to
      approximately 90 percent. Survey of pedestrians indicated positive response to
      the perceived safety and convenience posttreatment. CONCLUSIONS: Preliminary
      results of the case study suggest positive safety and convenience outcomes.
      Implications for pedestrian safety include less exposure to traffic and lower
      risk of serious injury, particularly for elderly pedestrians; convenience
      outcomes include shorter waiting times to cross and greater compliance to the
      crossing. A larger study is required to substantiate the findings.

PMID- 24867574
TI  - The effects of primary enforcement laws and fine levels on seat belt usage in the
      United States.
AB  - BACKGROUND: Seat belt use in the United States increased from 11 percent in 1979
      to 86 percent in 2012. Most of this increase has been attributed to seat belt
      laws, primary law upgrades, and highly visible enforcement. There has been less
      research on the effect of fines on seat belt usage. METHODS: We examined law type
      and fine levels as predictors of seat belt use among fatally injured occupants of
      passenger vehicles from 1997 through 2008 using data from the Fatality Analysis
      Reporting System (FARS). Fine levels used were the statutory maximum base fines
      for a first offense. RESULTS: Having a primary enforcement law was associated
      with a 9 to 10 percentage point increase in seat belt use. An increase in the
      fine amount, from the current median level of $25 to a level of $60, was
      associated with a 3 percentage point increase in usage. An increase in fine from
      $25 to $100 was associated with a 6- to 7-point increase. Such increases were in
      addition to the effects of a shift from secondary to primary enforcement.
      DISCUSSION: The results of this study suggest that, in addition to current
      emphases on primary law upgrades and high-visibility enforcement of seat belt
      usage, increasing fine levels provides another viable strategy for increasing
      seat belt use. In addition, based on these results, states should consider
      publicizing such increases just as they publicize enforcement efforts.

PMID- 24867575
TI  - Mild to moderate dehydration combined with moderate alcohol consumption has no
      influence on simulated driving performance.
AB  - OBJECTIVE: Many people consume alcoholic beverages following a period of physical
      activity that results in fluid loss through sweating (e.g., after sports, work).
      Adequate rehydration following physical activity may not occur, consequently
      resulting in the consumption of alcohol in a dehydrated state. This may have
      serious implications for the safety of individuals operating motor vehicles.
      Therefore, this study investigated the impact of mild-moderate dehydration in
      combination with moderate alcohol consumption on simulated driving performance.
      METHODS: Fourteen healthy males participated in a placebo-controlled crossover
      design study involving 4 experimental trials (separated by 4 days or more). In
      each trial, participants were dehydrated by ~2 percent body mass through
      exercise. After a 30-min recovery, participants completed a 15-min computerized
      simulated driving task (drive 1). In 2 of the trials, participants were provided
      with water equivalent to either 50 or 150 percent body mass loss and also
      received salt capsules (NaCl, 50 mmol/L). A set volume of alcohol or placebo was
      then consumed in each trial, incorporating the conditions: dehydration-placebo
      (DP), dehydration-alcohol (DA), partial rehydration-alcohol (PA), and full
      rehydration-alcohol (FA). The volume of the alcoholic beverage was individually
      calculated and intended to raise the blood alcohol content (BAC) to ~0.05
      percent. The same driving task was then readministered (drive 2). Primary outcome
      measures of driving consisted of standard deviation of lateral position (SDLP),
      number of side and center line crossings (LC), number of failures to stop at red
      traffic signals (FTS), number of impacts/collisions with other vehicles or
      objects (IMP), and time to collision with a specified lead vehicle (TTC). In
      addition, reaction time (RT) and incorrect inhibition response (IIR) behavior to
      critical events were collected throughout each experimental drive. Subjective
      ratings of mood and estimates of alcohol intoxication and driving impairment were
      also recorded in each trial. RESULTS: No effects of trial condition were observed
      on any of the driving performance measures or on subjective ratings of mood,
      alcohol intoxication, and driving impairment. SDLP was higher following the
      consumption of alcohol compared to the placebo trial. However, no differences in
      SDLP were recorded between the alcohol trials, indicating that hydration level
      had no observable interaction with alcohol to influence SDLP performance.
      CONCLUSIONS: Overall, it appears that dehydration does not exacerbate impairment
      in driving performance caused by mild-moderate alcohol intoxication. Further
      research is required to clarify the effects of alcohol and dehydration at various
      alcohol doses.

PMID- 24867576
TI  - Gay and lesbian couples in Italy: comparisons with heterosexual couples.
AB  - Assessing couple relationships across diverse languages and cultures has
      important implications for both clinical intervention and prevention. This is
      especially true for nontraditional relationships potentially subject to various
      expressions of negative societal evaluation or bias. Few empirically validated
      measures of relationship functioning have been developed for cross-cultural
      applications, and none have been examined for their psychometric sufficiency for
      evaluating same-sex couples across different languages and cultures. The current
      study examined the psychometric properties of an Italian translation of the
      Marital Satisfaction Inventory - Revised (MSI-R), a 150-item 13-scale measure of
      couple relationship functioning, for its use in assessing the intimate
      relationships of gay and lesbian couples in Italy. Results for these couples were
      compared to data from heterosexual married and unmarried cohabiting couples from
      the same geographical region, as well as to previously published data for gay,
      lesbian, and unmarried heterosexual couples from the United States. Findings
      suggest that, despite unique societal pressures confronting Italian same-sex
      couples, these relationships appear resilient and fare well both overall and in
      specific domains of functioning compared to heterosexual couples both in Italy
      and the United States. 

PMID- 24867578
TI  - Individual larvae of the zebrafish mutant belladonna display multiple infantile
      nystagmus-like waveforms that are influenced by viewing conditions.
AB  - PURPOSE: Infantile nystagmus syndrome (INS) is characterized by involuntary eye
      oscillations that can assume different waveforms. Previous attempts to uncover
      reasons for the presence of several nystagmus waveforms have not led to a general
      consensus in the community. Recently, we characterized the belladonna (bel)
      zebrafish mutant strain, in which INS-like ocular motor abnormalities are caused
      by misprojection of a variable fraction of optic nerve fibers. Here we studied
      intrinsic and extrinsic factors influencing the occurrence of different waveforms
      in bel larvae. METHODS: Eye movements of bel larvae were recorded in the presence
      of a stationary grating pattern. Waveforms of spontaneous oscillations were
      grouped in three categories: "pendular," "unidirectional jerk," and
      "bidirectional jerk," and the occurrences of each category were compared within
      and between individual larvae. Moreover, the effects of the characteristics of a
      preceding optokinetic response (OKR), of the field of view, and of the eye
      orbital position were analyzed. RESULTS: The different waveform categories co
      occurred in most individuals. We found waveforms being influenced by the
      preceding OKR and by the field of view. Moreover, we found different kinds of
      relationships between orbital position and initiation of a specific waveform,
      including pendular nystagmus in a more eccentric orbital position, and
      differences among jerk oscillations regarding the beating direction of the first
      saccade or waveform amplitude. CONCLUSIONS: Our data suggest that waveform
      categories in bel larvae do not reflect the severity of the morphological
      phenotype but rather are influenced by viewing conditions.

PMID- 24867577
TI  - Effects of strabismic amblyopia on visuomotor behavior: part II. Visually guided
      reaching.
AB  - PURPOSE: To examine the effects of impaired spatiotemporal vision on reaching
      movements in participants with strabismic amblyopia and to compare their
      performance to those with strabismus only without amblyopia and to visually
      normal participants. METHODS: Sixteen adults with strabismic amblyopia, 14 adults
      with strabismus only, and 16 visually normal adults were recruited. Participants
      executed reach-to-touch movements toward targets presented randomly 5 degrees  or
      10 degrees  to the left or right of central fixation in three viewing conditions:
      both eyes, monocular amblyopic eye (nondominant eye for participants without
      amblyopia), and monocular fellow eye (dominant eye for participants without
      amblyopia). Visual feedback of the target was removed on 50% of the trials at the
      initiation of reaching. RESULTS: Both groups with abnormal binocular vision
      (strabismic amblyopia and strabismus only) had reach latency, accuracy, and
      precision comparable to visually normal participants when viewing with both eyes
      and fellow (dominant) eye. Latencies were significantly delayed by more than 30
      ms in all participants with reduced binocularity during amblyopic eye or
      nondominant eye viewing compared with controls (P < 0.0001). Participants with
      strabismic amblyopia and negative stereopsis also had reduced reach precision
      (i.e., increased variability) during amblyopic eye viewing. In contrast,
      participants with strabismus only and negative stereopsis had comparable
      precision across all viewing conditions. Participants with strabismus only and
      those with strabismic amblyopia used a similar motor strategy; regardless of
      viewing condition, reach peak acceleration was significantly reduced (P < 0.05)
      and the duration of acceleration phase was extended in comparison with visually
      normal participants. There were no significant differences for the deceleration
      phase. CONCLUSIONS: Participants with strabismic amblyopia and those with
      strabismus only attain relatively normal reach accuracy and precision. However,
      they use a different reach strategy that involves changing the motor plan. A
      similar compensatory strategy was reported previously in participants with
      anisometropic amblyopia. Our results provide further support that normal
      binocular vision during development provides important input for the development
      of visually guided reaching movements.

PMID- 24867580
TI  - Malnutrition and retinal vascular caliber in the elderly: the POLA study.
AB  - PURPOSE: The pathway linking late-life malnutrition to greater risk of
      cardiovascular disease is unclear. Microcirulatory changes assessed by retinal
      vascular caliber have been linked with increased risk of stroke and coronary
      heart disease. The purpose of this study was to examine whether retinal vascular
      calibers are associated with malnutrition in elderly subjects free of
      cardiovascular diseases. METHODS: This was a cross-sectional analysis of a
      community-dwelling cohort comprising 1145 individuals aged 60 years and older.
      Retinal vascular caliber was measured from fundus photographs using a
      semiautomated, standardized imaging software. Malnutrition was assessed using
      body mass index (BMI) < 18.5 kg/m(2) and biomarkers of protein malnutrition:
      plasma albumin and transthyretin. RESULTS: In a multivariate model controlling
      for cardiovascular risk factors, retinal venular caliber was related to BMI (P =
      0.0002) with an increased mean caliber for individuals with obesity and for those
      with low BMI. After multivariate adjustment for age, sex, hypertension, smoking,
      high-density lipoprotein (HDL) cholesterol, glomerular filtration rate and BMI,
      lower levels of albumin or transthyretin were associated with larger retinal
      venular caliber (P = 0.026 and P = 0.0018, respectively), that remain significant
      when adjusting for CRP (P = 0.040 and P = 0.0060, respectively) or orosomucoid (P
      = 0.034 and P = 0.0020, respectively). The relationships between retinal
      arteriolar caliber and BMI, albumin and transthyretin did not reach significance
      (P = 0.14, P = 0.12, and P = 0.15, respectively). CONCLUSIONS: Protein
      malnutrition was identified as an additional factor associated with retinal
      venular dilatation beyond inflammation. This suggests that early microvascular
      changes may be one of the underlying mechanisms of increased risk of
      cardiovascular disease observed in elderly subjects suffering from malnutrition.

PMID- 24867579
TI  - Serum-induced differentiation of human meibomian gland epithelial cells.
AB  - PURPOSE: We hypothesize that culturing immortalized human meibomian gland
      epithelial cells in serum-containing medium will induce their differentiation.
      The purpose of this investigation was to begin to test our hypothesis, and
      explore the impact of serum on gene expression and lipid accumulation in human
      meibomian gland epithelial cells. METHODS: Immortalized and primary human
      meibomian gland epithelial cells were cultured in the presence or absence of
      serum. Cells were evaluated for lysosome and lipid accumulation, polar and
      neutral lipid profiles, and gene expression. RESULTS: Our results support our
      hypothesis that serum stimulates the differentiation of human meibomian gland
      epithelial cells. This serum-induced effect is associated with a significant
      increase in the expression of genes linked to cell differentiation, epithelium
      development, the endoplasmic reticulum, Golgi apparatus, vesicles, and lysosomes,
      and a significant decrease in gene activity related to the cell cycle,
      mitochondria, ribosomes, and translation. These cellular responses are
      accompanied by an accumulation of lipids within lysosomes, as well as alterations
      in the fatty acid content of polar and nonpolar lipids. Of particular importance,
      our results show that the molecular and biochemical changes of immortalized human
      meibomian gland epithelial cells during differentiation are analogous to those of
      primary cells. CONCLUSIONS: Overall, our findings indicate that immortalized
      human meibomian gland epithelial cells may serve as an ideal preclinical model to
      identify factors that control cellular differentiation in the meibomian gland.

PMID- 24867581
TI  - Up-regulation of VEGF by retinoic acid during hyperoxia prevents retinal
      neovascularization and retinopathy.
AB  - PURPOSE: Retinopathy of prematurity (ROP) is directly associated with abnormal
      expression of retinal vascular endothelial growth factor (VEGF) in premature
      neonates. This study was to investigate whether the systemic administration of
      retinoic acid (RA) regulates retinal VEGF expression and prevents retinal
      neovascularization and retinopathy in the oxygen-induced retinopathy (OIR) mouse
      model. METHODS: C57BL/6 mice were subjected to OIR by exposure to 75% oxygen from
      postnatal day (P) 7 to 12 of age. RA was intraperitoneally injected daily to pups
      from P6 to P9. Retinal whole mount staining and image analysis, immunostaining,
      Western blotting, quantitative RT-PCR, TUNEL assay, and electroretinography were
      performed to evaluate the effects of RA on VEGF expression, retinal
      neovascularization, and retinal neuron functions. RESULTS: Systemic
      administration of RA in OIR mice promoted retinal VEGF mRNA and protein
      expression in phase I; the stabilized level of VEGF in phase I supported retinal
      vascular development and counteracted vaso-obliteration in OIR mice.
      Subsequently, the excessive generation of VEGF in phase II was attenuated; the
      retinal vascular leakage and apoptotic cells were significantly ameliorated. As a
      result, RA significantly prevented the development of hypoxia-induced retinal
      neovascularization and retinopathy in OIR mice and improved the functional
      recovery of retinal neurons downstream of photoreceptor cells as measured by
      focal electroretinography. CONCLUSIONS: Systemic administration of RA regulates
      retinal VEGF expression and supports retinal vascular development in OIR mouse
      model. We propose that systemic administration of RA to extremely low birth
      weight, preterm infants during oxygen therapy could potentially be an effective
      therapeutic approach for the prevention of ROP.

PMID- 24867583
TI  - Medication Regimen Complexity and Unplanned Hospital Readmissions in Older
      People.
AB  - BACKGROUND: Medication-related problems and adverse drug events are leading
      causes of preventable hospitalizations. Few previous studies have investigated
      the possible association between medication regimen complexity and unplanned
      rehospitalization. OBJECTIVE: To investigate the association between discharge
      medication regimen complexity and unplanned rehospitalization over a 12-month
      period. METHOD: The prospective study comprised patients aged >=70 years old
      consecutively admitted to a Geriatrics Evaluation and Management (GEM) unit
      between October 2010 and December 2011. Medication regimen complexity at
      discharge was calculated using the 65-item validated Medication Regimen
      Complexity Index (MRCI). Cox proportional-hazards regression was used to compute
      unadjusted and adjusted hazard ratios (HRs) with 95% CIs for factors associated
      with rehospitalization over a 12-month follow-up period. RESULT: Of 163 eligible
      patients, 99 patients had one or more unplanned hospital readmissions. When
      adjusting for age, sex, activities of daily living, depression, comorbidity,
      cognitive status, and discharge destination, MRCI (HR = 1.01; 95% CI = 0.81
      1.26), number of discharge medications (HR = 1.01; 95% CI = 0.94-1.08), and
      polypharmacy (>=9 medications; HR = 1.12; 95% CI = 0.69-1.80) were not associated
      with rehospitalization. In patients discharged to nonhome settings, there was an
      association between rehospitalization and the number of discharge medications (HR
      = 1.12; 95% CI = 1.01-1.25) and polypharmacy (HR = 2.24; 95% CI = 1.02-4.94) but
      not between rehospitalization and MRCI (HR = 1.32; 95% CI = 0.98-1.78).
      CONCLUSION: Medication regimen complexity was not associated with unplanned
      hospital readmission in older people. However, in patients discharged to nonhome
      settings, the number of discharge medications and polypharmacy predicted
      rehospitalization. A patient's discharge destination is an important factor in
      unplanned medication-related readmissions.

PMID- 24867582
TI  - Regulation of retinal inflammation by rhythmic expression of MiR-146a in diabetic
      retina.
AB  - PURPOSE: Chronic inflammation and dysregulation of circadian rhythmicity are
      involved in the pathogenesis of diabetic retinopathy. MicroRNAs (miRNAs) can
      regulate inflammation and circadian clock machinery. We tested the hypothesis
      that altered daily rhythm of miR-146a expression in diabetes contributes to
      retinal inflammation. METHODS: Nondiabetic and STZ-induced diabetic rats kept in
      12/12 light/dark cycle were killed every 2 hours over a 72-hour period. Human
      retinal endothelial cells (HRECs) were synchronized with dexamethasone.
      Expression of miR-146a, IL-1 receptor-associated kinase 1 (IRAK1), IL-1beta, VEGF
      and ICAM-1, as well as clock genes was examined by real-time PCR and Western
      blot. To modulate expression levels of miR-146a, mimics and inhibitors were used.
      RESULTS: Diabetes inhibited amplitude of negative arm (per1) and enhanced
      amplitude of the positive arm (bmal1) of clock machinery in retina. In addition
      to clock genes, miR-146a and its target gene IRAK1 also exhibited daily
      oscillations in antiphase; however, these patterns were lost in diabetic retina.
      This loss of rhythmic pattern was associated with an increase in ICAM-1, IL-beta,
      and VEGF expression. Human retinal endothelial cells had robust miR-146a
      expression that followed circadian oscillation pattern; however, HRECs isolated
      from diabetic donors had reduced miR-146a amplitude but increased amplitude of
      IRAK1 and ICAM-1. In HRECs, miR-146a mimic or inhibitor caused 1.6- and 1.7-fold
      decrease or 1.5- and 1.6-fold increase, respectively, in mRNA and protein
      expression levels of ICAM-1 after 48 hours. CONCLUSIONS: Diabetes-induced
      dysregulation of daily rhythms of miR-146a and inflammatory pathways under miR
      146a control have potential implications for the development of diabetic
      retinopathy.

PMID- 24867584
TI  - Confocal microscopy demonstrates association of LTBP-2 in fibrillin-1
      microfibrils and colocalisation with perlecan in the disc cell pericellular
      matrix.
AB  - Comparative immunolocalisations of latent transforming growth factor-beta-1
      binding protein (LTBP)-2, fibrillin-1, versican and perlecan were undertaken in
      foetal human and wild type C57BL/6 mouse and Hspg2 exon 3 null HS deficient mouse
      intervertebral discs (IVDs). LTBP-2 was a prominent pericellular component of
      annular fibrochondrocytes in the posterior annulus fibrosus (AF), interstitial
      matrix adjacent to nucleus pulposus (NP) cells and to fibrillar and cell
      associated material in the anterior AF of the human foetal IVD and also displayed
      a pericellular localisation pattern in murine IVDs. Perlecan and LTBP-2 displayed
      strong pericellular colocalisation patterns in the posterior AF and to fibrillar
      material in the outer anterior AF in the foetal human IVD. Versican was a
      prominent fibril-associated component in the posterior and anterior AF, localised
      in close proximity to fibrillin-1 in fibrillar arrangements in the cartilaginous
      vertebral rudiments around paraspinal blood vessels, to major collagen fibre
      bundles in the anterior and posterior AF and shorter fibres in the NP. Fibrillin
      1 was prominent in the outer anterior AF of the human foetal IVD and in fibres
      extending from the AF into the cartilaginous vertebral rudiments. LTBP-2 was
      prominently associated with annular fibrils containing fibrillin-1, versican was
      localised in close proximity to these but not specifically with LTBP-2. The
      similar deposition levels of LTBP-2 observed in the AF of the Hspg2 exon 3 null
      and wild type murine IVDs indicated that perlecan HS was not essential for LTBP-2
      deposition but colocalisation of LTBP-2 with perlecan in the foetal human IVD was
      consistent with HS mediated interactions which have already been demonstrated in
      vitro. 

PMID- 24867585
TI  - Tuning of the ground state in electron doped anthracene.
AB  - High quality bulk samples of anthracene (AN) doped with potassium (K) in 1 : 1
      and 2 : 1 stoichiometries were successfully prepared by a method involving a room
      temperature solid-state mechanical diffusion process prior to intercalation
      reactions during heat treatment, and their physical properties were studied using
      both magnetic and optical measurements. The transfer of almost one electron from
      K to AN in K1(AN) was confirmed by SQUID and ESR measurements. A pronounced
      magnetic hump centered at 150 K associated with antiferromagnetic interactions
      was observed, which can most likely be interpreted in terms of on-site Coulomb
      repulsions of the Mott insulating states. Optical spectra of K1(AN) clearly
      showed the insulating states, as well as the electron occupation of the LUMO
      derived band of AN. Our results demonstrated tuning of the ground state of a
      typical bulk hydrocarbon by alkali metal intercalation. 

PMID- 24867586
TI  - The value and contribution of qualitative research to inform nurse education and
      policy in response to the child's experience of hospital.
AB  - The aim of this article is to consider the value of qualitative research to
      inform nurse education and policy for the hospitalized child and young person
      (CYP). The theoretical issues and tensions inherent in qualitative research with
      children and young people's nursing are presented in conjunction with a
      discussion and analysis of how the epistemological and ontological concepts
      underpin and guide research. It is then followed by an exploration of their
      influence on enabling nurses to understand the CYP's perspective, before finally
      leading to an analysis of the impact on the development of policy and research. 

PMID- 24867587
TI  - Development of live attenuated influenza vaccines against pandemic influenza
      strains.
AB  - Avian and animal influenza viruses can sporadically transmit to humans, causing
      outbreaks of varying severity. In some cases, further human-to-human virus
      transmission does not occur, and the outbreak in humans is limited. In other
      cases, sustained human-to-human transmission occurs, resulting in worldwide
      influenza pandemics. Preparation for future pandemics is an important global
      public health goal. A key objective of preparedness is to gain an understanding
      of how to design, test, and manufacture effective vaccines that could be
      stockpiled for use in a pandemic. This review summarizes results of an ongoing
      collaboration to produce, characterize, and clinically test a library of live
      attenuated influenza vaccine strains (based on Ann Arbor attenuated Type A
      strain) containing protective antigens from influenza viruses considered to be of
      high pandemic potential. 

PMID- 24867588
TI  - Blood stream infection in patients undergoing systematic off-pump coronary artery
      bypass: incidence, risk factors, outcome, and associated pathogens.
AB  - BACKGROUND: Blood stream infection (BSI) is a major cause of mortality and
      morbidity for patients undergoing cardiac surgery. However, information is
      lacking about patients undergoing off-pump coronary artery bypass (OPCAB). The
      purpose of this study was to assess the incidence, risk factors, outcome and
      associated pathogens of BSI after OPCAB. METHODS: One thousand ten consecutive
      patients undergoing OPCAB between 2001 and 2012 were included in a retrospective
      case-control study. A propensity-matched control was used for risk factor
      analysis. RESULTS: Of the 1,010 patients, 26 patients (2.6%) had 32 episodes of
      BSI after surgery, which occurred at a median of 14 d after surgery. Gram
      negative bacilli and gram-positive cocci were distributed equally. Methicillin
      resistant Staphylococcus aureus was the pathogen identified most frequently, and
      the most common source of infection was a surgical site. The hospital mortality
      rate was 54%. By univariable analysis, diabetes mellitus, pre-operative renal
      impairment, pre-operative low hemoglobin, pre-operative endotracheal intubation,
      dialysis before or after surgery, cardiogenic shock, left ventricular ejection
      fraction of less than 40%, non-elective surgery, low number of distal
      anastomoses, atrial fibrillation after surgery, and re-operation for bleeding
      were significant risk factors. By multivariable analysis, the independent risk
      factors were left ventricular ejection fraction of less than 40%, low number of
      distal anastomoses, atrial fibrillation after surgery, and dialysis after
      surgery. CONCLUSIONS: Blood stream infections remained a common complication
      after OPCAB, and the mortality was high. Gram-negative bacilli and gram-positive
      cocci were distributed equally. Methicillin-resistant S. aureus was the pathogen
      identified most frequently. Preventive tactics should target likely pathogens and
      high-risk patients undergoing OPCAB.

PMID- 24867589
TI  - Microsurgical debulking procedure after free lymph node flap transfer.

PMID- 24867591
TI  - Effects of Chili Treatment on Gastrointestinal and Rectal Sensation in Diarrhea
      predominant Irritable Bowel Syndrome: A Randomized, Double-blinded, Crossover
      Study.
AB  - BACKGROUND/AIMS: Whether, chronic chili ingestion can desensitize transient
      receptor potential vanilloid type 1 receptors in gastrointestinal (GI) tract
      leading to decrease GI symptoms and sensation in diarrhea-predominant irritable
      bowel syndrome (IBS-D) patients has not been well explored. The aim of this study
      was to determine the effects of 6-week chili treatment on postprandial GI
      symptoms and rectal sensation in response to balloon distention in IBS-D
      patients. METHODS: Sixteen IBS-D patients received placebo or chili capsules
      before meals 3 times/day for 6 weeks in a randomized, double-blinded, crossover
      fashion with 4-week washout period. Postprandial GI symptoms were evaluated. All
      patients underwent a rectal barostat study to evaluate rectal sensory threshold
      at the end of each treatment. RESULTS: The maximum postprandial abdominal burning
      scores were similar between both treatments at baseline (1.4 [0.0-2.0] vs. 1.1
      [0.0-2.8], P > 0.05) but were significantly decreased after chili (0.0 [0.0-0.5]
      vs. 0.3 [0.0-1.6], P < 0.05) at the end of treatment. The chili treatment
      significantly increased sensory threshold for the first rectal sensation (median
      [interquartile range]:16 [12-16] mmHg vs. 8 [8-16] mmHg, P < 0.05) however, there
      was no significant effect on rectal compliance (7.3 +/- 1.0 vs. 7.1 +/- 1.8
      mL/mmHg). Other postprandial GI symptoms did not vary significantly between both
      treatments at baseline and the end of treatment. CONCLUSIONS: In IBS-D patients,
      6-week chili ingestion significantly decreased postprandial abdominal burning and
      increased the rectal sensory threshold. These findings suggest a desensitization
      effect of chili ingestion on transient receptor potential vanilloid type 1
      receptors in the proximal gut and rectum.

PMID- 24867592
TI  - Hypertensive peristalsis: a rare cause of Dysphagia in a child.

PMID- 24867590
TI  - Development and bioorthogonal activation of palladium-labile prodrugs of
      gemcitabine.
AB  - Bioorthogonal chemistry has become one of the main driving forces in current
      chemical biology, inspiring the search for novel biocompatible chemospecific
      reactions for the past decade. Alongside the well-established labeling strategies
      that originated the bioorthogonal paradigm, we have recently proposed the use of
      heterogeneous palladium chemistry and bioorthogonal Pd(0)-labile prodrugs to
      develop spatially targeted therapies. Herein, we report the generation of
      biologically inert precursors of cytotoxic gemcitabine by introducing Pd(0)
      cleavable groups in positions that are mechanistically relevant for gemcitabine's
      pharmacological activity. Cell viability studies in pancreatic cancer cells
      showed that carbamate functionalization of the 4-amino group of gemcitabine
      significantly reduced (>23-fold) the prodrugs' cytotoxicity. The N
      propargyloxycarbonyl (N-Poc) promoiety displayed the highest sensitivity to
      heterogeneous palladium catalysis under biocompatible conditions, with a reaction
      half-life of less than 6 h. Zebrafish studies with allyl, propargyl, and benzyl
      carbamate-protected rhodamines confirmed N-Poc as the most suitable masking group
      for implementing in vivo bioorthogonal organometallic chemistry. 

PMID- 24867593
TI  - A comparative study of nano-scale coatings on gold electrodes for bioimpedance
      studies of breast cancer cells.
AB  - The relative sensitivity of standard gold microelectrodes for electric cell
      substrate impedance sensing was compared with that of gold microelectrodes coated
      with gold nanoparticles, carbon nanotubes, or electroplated gold to introduce
      nano-scale roughness on the surface of the electrodes. For biological solutions,
      the electroplated gold coated electrodes had significantly higher sensitivity to
      changes in conductivity than electrodes with other coatings. In contrast, the
      carbon nanotube coated electrodes displayed the highest sensitivity to MDA-MB-231
      metastatic breast cancer cells. There was also a significant shift in the peak
      frequency of the cancer cell bioimpedance signal based on the type of electrode
      coating. The results indicate that nano-scale coatings which introduce varying
      degrees of surface roughness can be used to modulate the frequency dependent
      sensitivity of the electrodes and optimize electrode sensitivity for different
      bioimpedance sensing applications. 

PMID- 24867594
TI  - An exploratory spatial analysis of ALS incidence in Ireland over 17.5 years (1995
      July 2013).
AB  - INTRODUCTION: There has been much interest in spatial analysis of ALS to identify
      potential environmental or genetically caused clusters of disease. Results to
      date have been inconclusive. The Irish ALS register has been recently geocoded,
      presenting opportunity to perform a spatial analysis on national prospectively
      gathered data of incident cases over an 18-year period. METHODS: 1,645 cases of
      ALS in Ireland from January 1995 to July 2013 were identified from the Irish ALS
      register. 1,638 cases were successfully geocoded. Census data from four censuses:
      1996, 2002, 2006 & 2011 were used to calculate an average population for the
      period and standardized incidence rates (SIRs) were calculated for 3,355 areas
      (Electoral Divisions). Bayesian conditional auto-regression was applied to
      produce smoothed relative risks (RR). These were then mapped for all cases, males
      & females separately, and those under 55 vs over 55 at diagnosis. Bayesian and
      linear regression were used to examine the relationship between population
      density and RR. RESULTS: Smoothed maps revealed no overall geographical pattern
      to ALS incidence in Ireland, although several areas of localized increased risk
      were identified. Stratified maps also suggested localized areas of increased RR,
      while dual analysis of the relationship between population density and RR of ALS
      yielded conflicting results, linear regression revealed a weak relationship.
      DISCUSSION: In contrast to some previous studies our analysis did not reveal any
      large-scale geographic patterns of incidence, yet localized areas of moderately
      high risk were found in both urban and rural areas. Stratified maps by age
      revealed a larger number of cases in younger people in the area of County Cork-
      possibly of genetic cause. Bayesian auto-regression of population density failed
      to find a significant association with risk, however weighted linear regression
      of post Bayesian smoothed Risk revealed an association between population density
      and increased ALS risk.

PMID- 24867595
TI  - Metabolic and cardiovascular responses during voluntary pedaling exercise with
      electrical muscle stimulation.
AB  - PURPOSE: We aimed to test the effect of additional electrical muscle stimulation
      (EMS) during moderate-intensity voluntary pedaling exercise on metabolic and
      cardiovascular responses. METHODS: Eleven healthy male subjects performed
      moderate-intensity pedaling exercise at a constant workload (80% of ventilatory
      threshold) for 20 min while EMS was applied to thigh muscles from 5 to 10 min and
      from 15 to 20 min during the exercise. RESULTS: A significantly higher oxygen
      uptake (VO2), heart rate, and respiratory gas exchange ratio were observed during
      the exercise periods with EMS despite the constant workload. These changes were
      accompanied by an elevated blood lactate concentration, suggesting the existence
      of additional fast-twitch motor unit (MU) recruitment during the exercise with
      EMS. CONCLUSION: Our data suggest that the use of intermittent EMS during a
      constant load exercise mimics the high-intensity interval training, possibly due
      to additional fast-twitch MU recruitment and co-contractions of the quadriceps
      and hamstrings muscles, leading to higher anaerobic metabolism and a lower
      mechanical efficiency.

PMID- 24867598
TI  - Twisted subserosal leiomyoma in a non-gravid uterus: A rare cause of acute
      abdomen.

PMID- 24867597
TI  - Interactions of lecithinized superoxide dismutase with serum proteins and cells.
AB  - Superoxide dismutase covalently bound to four lecithin molecules (PC-SOD) is
      known to be retained in circulating blood for a prolonged period and has a high
      affinity for cells, resulting in beneficial therapeutic effects in animal disease
      models. In this study, we evaluated the interaction of PC-SOD with biological
      components, such as serum proteins and cells, to clarify the mechanism underlying
      the improved pharmacokinetics of SOD induced by lecithin chemical modification
      (lecithinization). PC-SOD was distributed in the plasma but not in blood cells
      after being added to the blood. PC-SOD formed a complex with serum protein(s)
      such as albumin, whereas unmodified SOD did not. The cellular content of PC-SOD
      was markedly higher than that of unmodified SOD, and was distributed in
      lysosomes. The pathway associated with the cellular uptake was found to involve
      clathrin-/caveolae-independent and cholesterol-sensitive endocytosis. Overall,
      our data indicated that the increased hydrophobicity of lecithinized SOD enhanced
      its association to both serum protein(s) and plasma membrane microdomains. The
      former inhibited SOD excretion and promoted long-term retention in circulating
      blood, whereas the latter enhanced internalization into cells via endocytosis.

PMID- 24867599
TI  - Synthesis and electronic structure of the first cyaphide-alkynyl complexes.
AB  - The novel complexes trans-[Ru(dppe)2(C=CR)(C=P)] (R = CO2Me, C6H4OMe), the first
      to incorporate cyaphide as part of a conjugated system, are obtained in facile
      manner. The electronic structure of these compounds is probed by X-ray, DFT and
      UV/Vis studies.

PMID- 24867596
TI  - Physiological characterization of vestibular efferent brainstem neurons using a
      transgenic mouse model.
AB  - The functional role of efferent innervation of the vestibular end-organs in the
      inner ear remains elusive. This study provides the first physiological
      characterization of the cholinergic vestibular efferent (VE) neurons in the
      brainstem by utilizing a transgenic mouse model, expressing eGFP under a choline
      acetyltransferase (ChAT)-locus spanning promoter in combination with targeted
      patch clamp recordings. The intrinsic electrical properties of the eGFP-positive
      VE neurons were compared to the properties of the lateral olivocochlear (LOC)
      brainstem neurons, which gives rise to efferent innervation of the cochlea. Both
      VE and the LOC neurons were marked by their negative resting membrane potential <
      75 mV and their passive responses in the hyperpolarizing range. In contrast, the
      response properties of VE and LOC neurons differed significantly in the
      depolarizing range. When injected with positive currents, VE neurons fired action
      potentials faithfully to the onset of depolarization followed by sparse firing
      with long inter-spike intervals. This response gave rise to a low response gain.
      The LOC neurons, conversely, responded with a characteristic delayed tonic firing
      upon depolarizing stimuli, giving rise to higher response gain than the VE
      neurons. Depolarization triggered large TEA insensitive outward currents with
      fast inactivation kinetics, indicating A-type potassium currents, in both the
      inner ear-projecting neuronal types. Immunohistochemistry confirmed expression of
      Kv4.3 and 4.2 ion channel subunits in both the VE and LOC neurons. The difference
      in spiking responses to depolarization is related to a two-fold impact of these
      transient outward currents on somatic integration in the LOC neurons compared to
      in VE neurons. It is speculated that the physiological properties of the VE
      neurons might be compatible with a wide-spread control over motion and gravity
      sensation in the inner ear, providing likewise feed-back amplification of abrupt
      and strong phasic signals from the semi-circular canals and of tonic signals from
      the gravito-sensitive macular organs. 

PMID- 24867600
TI  - Biodegradation of the X-ray contrast agent iopromide and the fluoroquinolone
      antibiotic ofloxacin by the white rot fungus Trametes versicolor in hospital
      wastewaters and identification of degradation products.
AB  - This paper describes the degradation of the X-ray contrast agent iopromide (IOP)
      and the antibiotic ofloxacin (OFLOX) by the white-rot-fungus Trametes versicolor.
      Batch studies in synthetic medium revealed that between 60 and 80% of IOP and
      OFLOX were removed when spiked at approximately 12 mg L(-1) and 10 mg L(-1),
      respectively. A significant number of transformation products (TPs) were
      identified for both pharmaceuticals, confirming their degradation. IOP TPs were
      attributed to two principal reactions: (i) sequential deiodination of the
      aromatic ring and (ii) N-dealkylation of the amide at the hydroxylated side chain
      of the molecule. On the other hand, OFLOX transformation products were attributed
      mainly to the oxidation, hydroxylation and cleavage of the piperazine ring.
      Experiments in 10 L-bioreactor with fungal biomass fluidized by air pulses
      operated in batch achieved high percentage of degradation of IOP and OFLOX when
      load with sterile (87% IOP, 98.5% OFLOX) and unsterile (65.4% IOP, 99% OFLOX)
      hospital wastewater (HWW) at their real concentration (MUg L(-1) level). Some of
      the most relevant IOP and OFLOX TPs identified in synthetic medium were also
      detected in bioreactor samples. Acute toxicity tests indicated a reduction of the
      toxicity in the final culture broth from both experiments in synthetic medium and
      in batch bioreactor. 

PMID- 24867603
TI  - Dose effects of caffeine ingestion on acute hormonal responses to resistance
      exercise.
AB  - AIM: The purpose of this study was to examine the dose effects of caffeine on
      acute hormonal responses to resistance exercise (RE). METHODS: Twelve university
      males who regularly performed RE participated in this study. Subjects performed
      one repetition maximum (1RM) test and four treatments in a counterbalanced order:
      high dose (HD, 6 mg.kg(-1)), medium dose (MD, 4 mg.kg(-1)), low dose (LD, 2
      mg.kg(-1)), and placebo (PLA). Subjects ingested caffeine 1 hour before RE and
      then performed RE (2 exercises, 3 sets of 10 repetitions at 75% of 1RM). Blood
      samples were collected before caffeine intake (pre-60), immediately before RE
      (pre-exe), and 0, 15, 30 min post RE (P0, P15, and P30, respectively) for
      analysis of serum testosterone, cortisol, insulin, glucose, lactate, and free
      fatty acid (FFA). Each experiment was separated by 7 days. Statistical analysis
      of two-way analysis of variance with repeated measures was applied. Statistical
      significance was set at alpha=0.05. RESULTS: The concentrations of FFA (pre-exe)
      were significantly elevated following the HD, MD, and LD ingestions of caffeine.
      The concentrations of testosterone (P0, P15, and P30) and cortisol (pre-exe, P0,
      P15, and P30) at HD were significantly increased. However, the responses of
      insulin (P0 and P15) at HD and MD were significantly decreased. CONCLUSION: The
      results of this study indicate that high doses of caffeine increase the responses
      of testosterone and cortisol. Moreover, moderate and high doses of caffeine
      attenuate the insulin responses.

PMID- 24867601
TI  - Disinfection of wastewater effluents with the Fenton-like process induced by
      electromagnetic fields.
AB  - This research work is focused on the application and assessment of effectiveness
      of the Fenton-like processes induced by radiofrequency for the inactivation of
      faecal bacteria (Escherichia coli and Enterococcus sp.) present in treated urban
      wastewater effluents. Fenton processes were carried out at near neutral pH (pH 5)
      with different iron sources, such as iron salts (ferric chloride, 5, 50 and 100
      mg/L Fe(3+)), magnetite (1 g/L) and clay (80 g/L), hydrogen peroxide (25 mg/L)
      and in absence and presence of radiofrequency. Two different electromagnetic
      field intensities (1.57 and 3.68 kA/m) were used in Fenton processes induced by
      radiofrequency. Different agents used in the Fenton processes induced by
      electromagnetic fields (iron source, hydrogen peroxide and RF) were analyzed
      individually and in combination under the same experimental conditions. First
      assays of ferromagnetic material/H2O2/radiofrequency processes achieved promising
      results in terms of bacterial inactivation. For instance,
      Fe(3+)/H2O2/Radiofrequency achieved a maximum level of E. coli inactivation of
      3.55 log after 10 min of treatment. These results are higher than those obtained
      in absence of radiofrequency. The thermal activation of iron atoms allows the
      Fenton reaction to intensify, increasing the final yield of the treatment. On the
      other hand, different behavior was observed in the inactivation of E. coli and
      Enterococcus sp. due to the structural differences between Gram-negative and Gram
      positive bacteria. 

PMID- 24867602
TI  - Trading oxidation power for efficiency: differential inhibition of photo
      generated hydroxyl radicals versus singlet oxygen.
AB  - The ability of reactive oxygen species (ROS) to interact with target pollutants
      is crucial for efficient water treatment using advanced oxidation processes
      (AOPs), and inhibition by natural organic matter (NOM) can significantly reduce
      degradation efficiency. We compare OH-based degradation (H2O2-UV) to (1)O2-based
      degradation (Rose Bengal) of several probe compounds (furfuryl alcohol,
      ranitidine, cimetidine) interacting in water containing background constituents
      likely to be found in treatment water such as natural organic matter (NOM) and
      phosphate, as well as in effluent from a waste-water treatment plant (WWTP).
      Hydroxyl radicals were much more susceptible to hindrance by all three background
      matrices (NOM, phosphate and WWTP effluent) tested, while (1)O2 was only slightly
      inhibited by NOM and not by phosphate or WWTP effluent. A mechanistic model
      accounting for this inhibition in terms of radical scavenging and inner filter
      effects was developed, and accurately simulated the results of the NOM
      interactions. These results underscore the importance of considering the effect
      of background constituents in the selection of photocatalysts and in the design
      of AOPs for emerging applications in tertiary treatment of wastewater effluent
      and disinfection of natural waters. 

PMID- 24867604
TI  - Reliability of the assessment of peripheral muscle fatigue induced by high
      intensity intermittent exercise.
AB  - AIM: Reliability of the assessment of peripheral fatigue induced in knee
      extensors by high-intensity intermittent running exercise (HIE) was established
      in ten amateur soccer players (age: 18+/-1, height: 178+/-5 cm, weight: 68+/-8
      kg). METHODS: Transcutaneous electrical stimulations before and after HIE
      determined muscle contractile properties on three separate occasions (T1, T2 and
      T3), each separated by 7 days. RESULTS: No significant differences were noted for
      any of the parameters measured (P=0.101). The ICC values for peak torque (PT)
      varied from moderate to high, with the exception of PT at 10-Hz calculated
      comparing T2 vs. T1 (range PRE=0.78-0.92; POST=0.76-0.97). The ICC derived from
      PT percentage decrements data were all low, with the exception of PT decrements
      at 1 Hz calculated comparing T3 vs. T2 (ICC=0.85, moderate). The TE for all
      contractile parameters obtained using 1-Hz and 100-Hz electrical stimulations
      were below 10%, including some that demonstrated a TE lower than 5%. Muscle
      contractile properties determined using 10-Hz stimulations showed a higher level
      of TE (range: 3.2-15.1%). Similar results were obtained for maximal rate of
      torque development and torque relaxation. CONCLUSION: From the results of this
      study it can be concluded that muscle contractile properties express a good level
      of reliability in baseline and postexercise measures following familiarization.

PMID- 24867605
TI  - Ultrasonographic evaluation of the shoulder in elite Italian beach volleyball
      players.
AB  - AIM: Beach volleyball is an overhead sport that subjects the hitting shoulder to
      intense functional loads. The purpose of this study is to identify
      ultrasonographically the prevalence of myotendinous alterations in professional
      Italian beach volleyball players at the Italian championship and to look for
      associations between ultrasound findings and the other data collected. METHODS:
      Fifty-three beach volleyball players (31 women, 22 men) were recruited during the
      second stage of the Italian championship held in July 2012 in Rome, Italy.
      Clinical history was obtained from all subjects, followed by physical exam. Each
      athlete completed a questionnaire regarding sports activities. Bilateral
      ultrasonographic evaluation of the shoulders was then performed. RESULTS:
      Calcific tendinopathy of the rotator cuff of the hitting shoulder was identified
      ultrasonographically in 30% of the athletes. The mean age of the athletes with
      calcific tendinopathy was older than subjects with other abnormalities on
      ultrasonographic examination (33.1 years vs. 25.8 years, t-test; P<0.0001).
      Impingement was recognized ultrasonographically in the hitting shoulder in 10 of
      the athletes (18.8%). The Neer's test was positive in the cases of anterior
      impingement (chi2; P<0.002). CONCLUSION: Calcific tendinopathy of the rotator
      cuff of the hitting shoulder in professional beach volleyball players has a
      prevalence of 30% ultrasonographically, greater than that reported in the general
      population. In these athletes, the presence of calcific tendinopathy correlates
      positively with age.

PMID- 24867606
TI  - Anti-obesity and anti-insulin resistance effects of tomato vinegar beverage in
      diet-induced obese mice.
AB  - This study investigated the mechanism of processed tomato vinegar beverage (TVB)
      mediated anti-obesity and anti-insulin resistance effects in high-fat diet (HF)
      induced obese mice. Oral administration of TVB (14 mL kg(-1) body weight) to HF
      fed mice for 6 weeks effectively reduced the body and visceral fat weight and
      significantly lowered plasma free fatty acid, triglyceride and hepatic
      triglyceride levels. TVB significantly increased fecal triglyceride excretion,
      both phosphorylated AMP-activated protein kinase (AMPK) and acetyl-CoA
      carboxylase (ACC) and peroxisome proliferator-activated receptor (PPAR)alpha
      protein levels in the liver, which were associated with increased fatty acid beta
      oxidation and carnitine palmitoyltransferase activities in HF-fed mice. TVB
      improved glucose tolerance, hyperinsulinemia and HOMA-IR levels in the HF + TVB
      group compared to the HF group. Additionally, TVB significantly increased
      glucokinase activity and decreased glucose-6-phosphatase activity in the liver,
      which enhanced glucose metabolism in obese mice. These results suggest that TVB
      prevents visceral obesity and insulin resistance via AMPK/PPARalpha-mediated
      fatty acid and glucose oxidation. 

PMID- 24867607
TI  - What is the best non-codeine postadenotonsillectomy pain management for children?

PMID- 24867608
TI  - Mid-range Ca2+ signalling mediated by functional coupling between store-operated
      Ca2+ entry and IP3-dependent Ca2+ release.
AB  - The versatility and universality of Ca(2+) signals stem from the breadth of their
      spatial and temporal dynamics. Spatially, Ca(2+) signalling is well studied in
      the microdomain scale, close to a Ca(2+) channel, and at the whole-cell level.
      However, little is known about how local Ca(2+) signals are regulated to
      specifically activate spatially distant effectors without a global Ca(2+) rise.
      Here we show that an intricate coupling between the inositol 1,4,5 trisphosphate
      (IP3) receptor, SERCA pump and store-operated Ca(2+) entry (SOCE) allows for
      efficient mid-range Ca(2+) signalling. Ca(2+) flowing through SOCE is taken up
      into the ER lumen by the SERCA pump, only to be re-released by IP3Rs to activate
      distal Ca(2+)-activated Cl(-) channels (CaCCs). This CaCC regulation contributes
      to setting the membrane potential of the cell. Hence functional coupling between
      SOCE, SERCA and IP3R limits local Ca(2+) diffusion and funnels Ca(2+) through the
      ER lumen to activate a spatially separate Ca(2+) effector. 

PMID- 24867609
TI  - Acute human T-lymphotropic virus type I-associated myelitis: a rare case
      successfully treated with intravenous pulse methylprednisolone.

PMID- 24867612
TI  - Upper eyelid retraction in the anophthalmic socket: review and survey of the
      Australian and New Zealand Society of Ophthalmic Plastic Surgeons (ANZSOPS).
AB  - PURPOSE: Unlike ptosis, upper eyelid retraction (ULR) is not a widely reported
      complication of the anophthalmic socket or post-enucleation socket syndrome
      (PESS). The clinical entity of post-enucleation ULR is investigated. METHODS: 1)
      Two cases of post-enucleation ULR presenting to a specialist oculoplastic center
      (South Australian Institute of Ophthalmology, Adelaide, Australia) are described,
      2) Single forced choice survey of 22 members of the Australian and New Zealand
      Society of Ophthalmic Plastic Surgeons regarding their clinical experience of ULR
      in anophthalmia, and 3) English literature review. RESULTS: One case of ULR
      occurred less than 1 year and the other several decades following enucleation,
      both cases underwent eyelid surgery. Eighty-two percent of oculoplastic surgeons
      surveyed believe ULR is a rare and late (50%) complication of anophthalmia and
      13.5% had never seen a case. Ninety-five percent indicated that ptosis is more
      common than retraction. A literature review supports the rarity of ULR in
      anophthalmia and a number of etiological factors are discussed. CONCLUSIONS:
      Upper eyelid retraction is a rare and often late complication of the anophthalmic
      socket. It occurs less commonly than ptosis as part of PESS, but increased
      recognition and reporting may improve the understanding of its true incidence and
      cause.

PMID- 24867613
TI  - Alterations in the time course of expression of the Nox family in the brain in a
      rat experimental cerebral ischemia and reperfusion model: effects of melatonin.
AB  - Ischemia-reperfusion (I/R) injury induces the generation of reactive oxygen
      species (ROS), which results in a poor prognosis for ischemic stroke patients.
      This study was designed to evaluate the time course of expression of the Nox
      family, a major source of ROS, and whether melatonin, a potent scavenger of ROS,
      influences these parameters in a rat model of cerebral I/R caused by middle
      cerebral artery occlusion (MCAO). After 2-hr occlusion, the filament was
      withdrawn to allow reperfusion. At 0, 3, 6, 12, 24, and 48 hr after reperfusion,
      brain tissue samples were obtained for assays. Among the Nox family, the mRNA and
      protein levels of Nox2 and Nox4 were increased both in the ischemic hemisphere
      and contralateral counterpart in the experimental I/R rats at 0 hr after
      reperfusion, peaked at 3 hr, and then returned to the basal level at 24 hr.
      Double-immunofluorescence staining further confirmed the expressions of Nox2 and
      Nox4 in three major types of brain cells, including neurons, astrocytes, and
      endothelial cells. In addition, melatonin (5 mg/kg) or its vehicle was injected
      intraperitoneally at 0.5 hr before MCAO. Compared with I/R + vehicle group,
      melatonin pretreatment diminished the increased expression of Nox2 and Nox4,
      reduced ROS levels, and inhibited cell apoptosis. Our findings suggested that the
      inhibition of Nox2 and Nox4 expressions by melatonin may essentially contribute
      to its antioxidant and anti-apoptotic effects during brain I/R. 

PMID- 24867610
TI  - Neural dysregulation during a working memory task in human immunodeficiency virus
      seropositive and hepatitis C coinfected individuals.
AB  - Cognitive and functional neural correlates of human immunodeficiency virus (HIV)
      are only partially understood at present. Variability in neural response, which
      has been noted in the literature, may relate to clinical factors associated with
      HIV, including time since HIV diagnosis, CD4 count and nadir, HIV viral load, and
      comorbid infectious processes, especially hepatitis C. The present investigation
      evaluated working memory-related functional neural activation in 26 HIV+
      participants, 28 demographically matched HIV-seronegative individuals, and 8 HIV+
      individuals with hepatitis C coinfection. Analyses examined impact of HIV
      infection duration, CD4 count and nadir, HIV viral load, and hepatitis C
      serostatus. Results showed that HIV-seronegative participants had fastest
      reaction times, and during the working memory task, HIV+ participants with
      hepatitis C coinfection showed strongest bias toward commission errors; however,
      signal detection (i.e., overall task performance) was equivalent across groups.
      Functional magnetic resonance imaging (fMRI) results showed HIV-related greater
      activation to an easier vigilance task and HIV-related lower activation to a more
      difficult working memory task, consistent with reduced cognitive reserve.
      Hepatitis C coinfection related to diffuse neural dysregulation. Correlational
      analyses suggested relationships of increasingly severe disease with poorer
      functioning in brain regions linked to error monitoring and attention regulation.

PMID- 24867614
TI  - Infectious hypodermal and hematopoietic necrosis virus from Brazil: Sequencing,
      comparative analysis and PCR detection.
AB  - A 3739 nucleotide fragment of Infectious hypodermal and hematopoietic necrosis
      virus (IHHNV) from Brazil was amplified and sequenced. This fragment contains the
      entire coding sequences of viral proteins, the full 3' untranslated region
      (3'UTR) and a partial sequence of 5' untranslated region (5'UTR). The genome
      organization of IHHNV revealed the three typical major coding domains: a left
      ORF1 of 2001 bp that codes NS1, a left ORF2 (NS2) of 1091 bp that codes NS2 and a
      right ORF3 of 990 bp that codes VP. Nucleotide and amino acid sequences of the
      three viral proteins were compared with putative amino acid sequences of viruses
      reported from different regions. Comparisons among genomes from different
      geographic locations reveal 31 nucleotide regions that are 100% similar,
      distributed throughout the genome. An analysis of secondary structure of UTR
      regions, revealed regions with high probability to form hairpins, that may be
      involved in mechanisms of viral replication. Additionally, a maximum likelihood
      analysis indicates that Brazilian IHHNV belongs to lineage III, in the infectious
      IHHNV group, and is clustered with IHHNV isolates from Hawaii, China, Taiwan,
      Vietnam and South Korea. A new nested PCR targeting conserved nucleotide regions
      is proposed to detect IHHNV.

PMID- 24867611
TI  - Glutamate metabolism and HIV-associated neurocognitive disorders.
AB  - HIV-1 infection can lead to neurocognitive impairment collectively known as HIV
      associated neurocognitive disorders (HAND). Although combined antiretroviral
      treatment (cART) has significantly ameliorated HIV's morbidity and mortality,
      persistent neuroinflammation and neurocognitive dysfunction continue. This review
      focuses on the current clinical and molecular evidence of the viral and host
      factors that influence glutamate-mediated neurotoxicity and neuropathogenesis as
      an important underlying mechanism during the course of HAND development. In
      addition, discusses potential pharmacological strategies targeting the
      glutamatergic system that may help prevent and improve neurological outcomes in
      HIV-1-infected subjects.

PMID- 24867616
TI  - Documentation of capacity and identification of substitute decisionmakers in
      Ontario.
AB  - Documenting capacity assessments and identifying substitute decisionmakers (SDMs)
      in healthcare facilities is ethically required for optimal patient care. Lack of
      such documentation has the potential to generate confusion and contention among
      patients, their family members, and members of the healthcare team. An overview
      of our research at the Ottawa Hospital and issues that influence the consistency
      of documentation in the Canadian context are presented here, as well as ideas for
      the mitigation of these issues and ways to encourage better documentation.

PMID- 24867615
TI  - Isolation and characterization of H7N9 avian influenza A virus from humans with
      respiratory diseases in Zhejiang, China.
AB  - In 2013, the novel reassortant avian-origin influenza A (H7N9) virus was reported
      in China. Through enhanced surveillance, infection by the H7N9 virus in humans
      was first identified in Zhejiang Province. Real-time reverse-transcriptase
      polymerase-chain-reaction (RT-PCR) was used to confirm the infection. Embryonated
      chicken eggs were used for virus isolation from pharyngeal swabs taken from
      infected human patients. The H7N9 isolates were first identified by the
      hemagglutination test and electron microscopy, then used for whole genome
      sequencing. Bioinformatics software was used to construct the phylogenetic tree
      and for computing the mean rate of evolution of the HA gene in H7Nx and NA in
      HxN9. Two novel H7N9 avian influenza A viruses (A/Zhejiang/1/2013 and
      A/Zhejiang/2/2013) were isolated from the positive infection cases. Substitutions
      were found in both Zhejiang isolates and were identified as human-type viruses.
      All phylogenetic results indicated that the novel reassortant in H7N9 originated
      in viruses that infected birds. The sequencing and phylogenetic analysis of the
      whole genome revealed the mean rate of evolution of the HA gene in H7NX to be
      5.74E-3 (95% Highest posterior density: 3.8218E-3 to 7.7873E-3) while the NA gene
      showed 2.243E-3 (4.378E-4 to 3.79E-3) substitutions per nucleotide site per year.
      The novel reassortant H7N9 virus was confirmed by molecular methods to have
      originated in poultry, with the mutations occurring during the spread of the H7N9
      virus infection. Live poultry markets played an important role in whole H7N9
      circulation. 

PMID- 24867617
TI  - Inguinal hernia as a presentation of testicular feminization.
AB  - We present a case of a 20-year-old female who was admitted to our department for
      an elective inguinal hernia repair. An oval-shaped mass was found in the hernia
      sac during the surgery that was suspected to be an ovary. Histological
      examination revealed testicular tissue. Further evaluation confirmed testicular
      feminization. She underwent laparoscopic orchiectomy and hernia repair from the
      contralateral side 3 months later. 

PMID- 24867619
TI  - Direct catalytic access to N-silylated enamines from enolizable imines and
      hydrosilanes by base-free dehydrogenative Si-N coupling.
AB  - A procedure for the synthesis of otherwise difficult-to-make N-silylated
      enamines, that is masked enamines derived from primary amines, is reported. The
      approach is based on formation of a silyliminium ion and subsequent abstraction
      of the acidified alpha-proton rather than alpha-deprotonation of the enolizable
      imine followed by reaction with an electrophilic silicon reagent. The silicon
      electrophile, stabilized by a sulfur atom, is generated by cooperative activation
      of an Si-H bond at the Ru-S bond of a tethered ruthenium(II) thiolate complex.
      After transfer of the silicon cation onto the imine nitrogen atom, the remaining
      ruthenium(II) hydride fulfills the role of the base. Deprotonation and release of
      dihydrogen close the catalytic cycle. The net reaction is a dehydrogenative Si-N
      coupling of enolizable imines and hydrosilanes.

PMID- 24867618
TI  - A conjugate thermo-electric model for a composite medium.
AB  - Electrical transmission signals have been used for decades to characterize the
      internal structure of composite materials. We theoretically analyze the
      transmission of an electrical signal through a composite material which consists
      of two phases with different chemical compositions. We assume that the
      temperature of the biphasic system increases as a result of Joule heating and its
      electrical resistivity varies linearly with temperature; this last consideration
      leads to simultaneously study the electrical and thermal effects. We propose a
      nonlinear conjugate thermo-electric model, which is solved numerically to obtain
      the current density and temperature profiles for each phase. We study the effect
      of frequency, resistivities and thermal conductivities on the current density and
      temperature. We validate the prediction of the model with comparisons with
      experimental data obtained from rock characterization tests. 

PMID- 24867620
TI  - The relationship between dietary lipids and serum visfatin and adiponectin levels
      in postmenopausal women.
AB  - Cardiovascular diseases (CVD) are the leading cause of death in humans,
      particularly in postmenopausal women. Inflammation has been shown to play a basic
      role in the development of CVD. In light of the involvement of adipocytokines and
      dietary lipids in the induction of inflammation in CVD, this study was conducted
      to investigate the potential relationship between dietary lipids and two well
      known adipocytokines, visfatin and adiponectin. A total of 374 postmenopausal
      women were randomly selected from 13 geographical clusters in Bushehr port. Serum
      visfatin and adiponectin were determined with an enzyme-linked immunosorbant
      assay technique and current dietary intake was recorded with a food frequency
      questionnaire and a 3-day recall. Each food and beverage was analyzed for macro-
      and micronutrient content. Bivariate correlation analysis showed a correlation
      between serum visfatin level and dietary SFA, n-6 PUFA and cholesterol intake. In
      multiple regression analyses, serum visfatin levels showed a significant positive
      correlation with dietary SFA (beta=0.06, p=0.01), PUFA (beta=0.02, p=0.02) and
      cholesterol (beta=0.005, p=0.002) after controlling for age, diabetes, total
      energy intake and BMI. There was no significant relationship between dietary MUFA
      intake and serum visfatin level. No significant correlations were found between
      age- and BMI-adjusted adiponectin and dietary SFA, MUFA or n-6 PUFA intake
      (p>0.05). We found a positive relationship between dietary SFA, PUFA and
      cholesterol with serum visfatin level in postmenopausal women, and conclude that
      the postmenopause-induced inflammatory responses may be modulated at least in
      part by dietary modification. 

PMID- 24867621
TI  - Immunological aspects of metritis in dairy cows: a review.
AB  - This paper reviews puerperal metritis in the cow, particularly the complex and
      multi-factorial pathogenesis characterized by an altered cross-talk among
      infectious agents, endocrine and immune systems. Uterine infections impair
      fertility and is one of the main causes of economic losses in dairy production.
      The early postpartum is a period characterized by an increased exposition to
      infectious agents and the disruption of the metabolic homeostasis, leading to
      endocrine and immunologic disorders. Dysregulation of uterine defence mechanisms
      results in the development of metritis. Because there is a complex interaction
      between infectious, endocrine and immune factors during metritis, there is need
      to use safer and cheaper drugs which are able to strengthen the anti-infective
      actions of the routine therapies. 

PMID- 24867622
TI  - Feasibility of a randomized controlled intervention with physical activity in
      participants with impaired glucose tolerance recruited by FINDRISC: A pilot
      study.
AB  - BACKGROUND: This study aimed to explore the feasibility and effect of an
      intervention in clinical practice with isolated physical activity in individuals
      with IGT, recruited by the FINDRISC questionnaire. METHODS: The questionnaire was
      sent to a population of 9734 individuals, 35-75 years old, in Sweden. Those with
      a risk score >=15 were encouraged to perform an oral glucose tolerance test.
      Individuals with IGT were invited to participate in a randomized controlled trial
      with a focus on physical activity. The participants were allocated to one of
      three arms; basic intervention, intensive intervention or to care as usual. A
      total of 52 individuals were carefully examined and questionnaires about diet and
      lifestyle were completed at baseline and after one year. All analyses were
      adjusted for differences in age and sex, and calorie intake when relevant.
      RESULTS: The prevalence of chronic diseases in the study population was high,
      creating considerable difficulties in conducting a standardized test for fitness.
      Waist circumference (p=0.020), sagittal diameter (p=0.035), body weight (p=0.038)
      and BMI (p=0.043) decreased significantly more in the intensive care group than
      in care as usual and the basic care group. However, the significance was
      abolished when differences in energy intake were accounted for. CONCLUSIONS: In
      an intention to treat, prospective lifestyle interventions with physical activity
      are feasible, but a high prevalence of comorbidities needs to be considered.
      Also, an intervention focused on isolated physical activity inevitably led to
      changes in diet with weight loss and significant improvement of essential risk
      factors in spite of the participants' burden of chronic diseases.

PMID- 24867626
TI  - Transcatheter therapies for mitral regurgitation: a professional society overview
      from the american college of cardiology, the american association for thoracic
      surgery, society for cardiovascular angiography and interventions foundation, and
      the society of thoracic surgeons.

PMID- 24867627
TI  - Transient right internal thoracic arterial graft kink related to respiratory
      movements: documentation of its existence, relevance and proposed management.
AB  - In this case report, we provide the first detailed description of an intermittent
      mechanical kink of a right internal thoracic artery (ITA) graft to the left
      anterior descending coronary artery secondary to respiratory movements, and its
      assessment by pressure wire derived fractional flow reserve (FFR). The patient
      presented with recurrent unstable angina and documented anterior/anterolateral
      ischemia. Persistent symptoms were attributed to the ITA kink and stenting was
      planned on clinical grounds. However, the lesion proved not physiologically
      significant when FFR was assessed after intermittency related to respiratory
      movements was documented. Complex stenting was therefore avoided and medical
      therapy was prescribed for distal diagonal disease. We therefore propose that
      intermittency should be actively investigated when a kink is documented in a
      coronary bypass graft by conventional angiography (using dedicated angiographic
      evaluation in maximal inspiration and expiration). Furthermore, when this type of
      lesion is encountered, we suggest that it should be assessed physiologically
      using pressure wire derived FFR before potentially complex interventions are
      considered.

PMID- 24867628
TI  - Complete Blalock-Taussig shunt obstruction in < 24 hours post-operative period in
      a neonate treated emergently using transcatheter angioplasty and low dose local
      recombinant TPA.
AB  - A 12-day-old infant with pulmonary atresia, intact ventricular septum, and
      pulmonary blood flow through a ductus arteriosus developed complete shunt
      obstruction within 12 hr of creation of a modified Blalock-Taussig shunt. Low
      dose recombinant tissue plasminogen activator was administered locally as two
      0.03 mg/kg bolus injections and was followed by balloon angioplasty. This
      resulted in complete recanalization of the shunt without any hemorrhagic
      complications.

PMID- 24867629
TI  - Enhancing the thermostability of a cold-active lipase from Penicillium cyclopium
      by in silico design of a disulfide bridge.
AB  - Cysteine mutants of a cold-active lipase (PcLipI) from Penicillium cyclopium were
      designed by the software Disulfide by Design Ver. 1.20 in an effort to improve
      enzyme thermostability by addition of a disulfide bridge. Those mutants predicted
      by molecular dynamics simulation to have better thermostability than the wild
      type were first expressed in Escherichia coli BL21(DE3) and then, for further
      investigation, in Pichia pastoris GS115. By replacing Val248 and Thr251 with
      cysteines to create a disulfide bridge, the recombinant lipases reE-PcLipV248C
      T251C (expressed in E. coli) and reP-PcLipV248C-T251C (expressed in P. pastoris)
      were obtained. Both had enhanced thermostability with half-lives at 35  degrees C
      about 4.5- and 12.8-fold longer than that of the parent PcLipI expressed in E.
      coli and P. pastoris, respectively. The temperature optima of reE-PcLipV248C
      T251C and reP-PcLipV248C-T251C were 35 and 30  degrees C, which were each 5 
      degrees C higher than those of the parent PcLipI expressed in E. coli and P.
      pastoris. The K ms of reE-PcLipV248C-T251C and reP-PcLipV248C-T251C toward
      tributyrin were 53.2 and 39.5 mM, while their V maxs were 1,460 and 3,800 U/mg,
      respectively. PcLipV248C-T251C had better thermostability and catalytic
      efficiency than the other mutants and the parent PcLipI.

PMID- 24867630
TI  - Flow-based impedimetric immunosensor for aflatoxin analysis in milk products.
AB  - Label-free detection technique based on impedance was investigated for aflatoxin
      M1 (AFM1) and aflatoxin M2 (AFM2) analysis in milk products. The impedance change
      resulting from antigen-antibody interaction was studied using a two-electrode
      setup made up of silver (Ag) wire. Processed milk such as drinking yogurt and
      flavored milk samples were analyzed in a flow-based setup. Two microflow pumps
      were used to construct the flow system where analytes (AFM1 and AFM2) were
      injected and impedance was measured using functionalized Ag wire electrodes. The
      flow system was optimized by adjusting both inlet and outlet flows to maintain
      the reaction volume optimum for impedance measurements. Using Bode plot, the
      matrix effect was investigated for detection of AFM1 and AFM2 in various
      matrices. Good recoveries were obtained even at low-AFM1 concentrations in the
      range of 1-100 pg/mL. The influence of AFM2 on the detection of AFM1 was also
      investigated. The proposed method provides good scope for online monitoring of
      such hazardous toxins in milk products. 

PMID- 24867632
TI  - Changes in Ocular Manifestations of Behcet Disease in Korean Patients over Time:
      A Single-center Experience in the 1990s and 2000s.
AB  - PURPOSE: To analyze chronological changes in ocular manifestations of Behcet's
      disease (BD) in Korean patients. METHODS: Ocular findings were retrospectively
      analyzed from medical records of patients diagnosed with BD between 1994 and 2010
      and divided into two groups according to the date of their first visit to our
      ophthalmology department. Group A began care between 1994 and 2000, and Group B
      between 2004 and 2010. RESULTS: Fifty-six patients (83 eyes) were included in
      analyses. There was a significant decrease in the number of complete BD cases in
      Group B compared to Group A, and fewer patients had genital lesions in Group B.
      Mean visual acuity was better, and more patients had good vision in Group B than
      in Group A at the one and two year follow-up. CONCLUSIONS: The severity of BD has
      decreased over the past two decades, allowing BD patients with ocular involvement
      to have better visual prognoses.

PMID- 24867631
TI  - Nanodiamond-mitoxantrone complexes enhance drug retention in chemoresistant
      breast cancer cells.
AB  - Chemoresistance is a prevalent issue that accounts for the vast majority of
      treatment failure outcomes in metastatic cancer. Among the mechanisms of
      resistance that markedly decrease treatment efficacy, the efflux of drug
      compounds by ATP-binding cassette (ABC) transporter proteins can impair adequate
      drug retention by cancer cells required for therapeutic cytotoxic activity. Of
      note, ABC transporters are capable of effluxing several classes of drugs that are
      clinical standards, including the anthracyclines such as doxorubicin, as well as
      anthracenediones such as mitoxantrone. To address this challenge, a spectrum of
      nanomaterials has been evaluated for improved drug retention and enhanced
      efficacy. Nanodiamonds (NDs) are emerging as a promising nanomaterial platform
      because they integrate several important properties into a single agent. These
      include a uniquely faceted truncated octahedral architecture that enables potent
      drug binding and dispersibility in water, scalably processed ND particles with
      uniform diameters of approximately 5 nm, and a demonstrated ability to improve
      drug tolerance while delaying tumor growth in multiple preclinical models, among
      others. This work describes a ND-mitoxantrone complex that can be rapidly
      synthesized and mediates marked improvements in drug efficacy. Comprehensive
      complex characterization reveals a complex with favorable drug delivery
      properties that is capable of improving drug retention and efficacy in an MDA-MB
      231-luc-D3H2LN (MDA-MB-231) triple negative breast cancer cell line that was
      lentivirally transduced for resistance against mitoxantrone. Findings from this
      study support the further evaluation of ND-MTX in preclinical dose escalation and
      safety studies toward potentially clinical validation. 

PMID- 24867633
TI  - The effect of anterior cruciate ligament injury on bone curvature: exploratory
      analysis in the KANON trial.
AB  - OBJECTIVE: Investigate the 5-year longitudinal changes in bone curvature after
      acute anterior cruciate ligament (ACL) injury, and identify predictors of such
      changes. METHODS: In the KANON-trial (ISRCTN 84752559), 111/121 young active
      adults with an acute ACL tear to a previously un-injured knee had serial 1.5 T MR
      images from baseline (within 5 weeks from injury) to 5 years after injury. Of
      these, 86 had ACL reconstruction (ACLR) performed early or delayed, 25 were
      treated with rehabilitation alone. Measures of articulating bone curvature were
      obtained from computer-assisted segmentation of MR images. Curvature (mm(-1)) was
      determined for femur, tibia, medial/lateral femur, trochlea, medial/lateral
      tibia. Age, sex, treatment, BMI, meniscal injury, osteochondral fracture on
      baseline MR images were tested for association. RESULTS: Over 5 years, curvature
      decreased in each region (P < 0.001) suggesting flattening of convex shapes and
      increased concavity of concave shapes. A higher BMI was associated with
      flattening of the femur (P = 0.03), trochlea (P = 0.007) and increasing concavity
      of the lateral tibia (LT) (P = 0.011). ACLR, compared to rehabilitation alone,
      was associated with flatter curvature in the femur (P < 0.001), medial femoral
      condyle (P = 0.006) and trochlea (P = 0.003). Any meniscal injury at baseline was
      associated with a more flattened curvature in the femur (P = 0.038), trochlea (P
      = 0.039), lateral femoral condyle (P = 0.034) and increasing concavity of the LT
      (P = 0.048). CONCLUSION: ACL injury is associated with significant changes in
      articulating bone curvature over a 5 year period. Higher BMI, baseline meniscal
      injury and undergoing ACL reconstruction (as distinct from undergoing
      rehabilitation alone) are all associated with flattening of the articulating
      bone.

PMID- 24867634
TI  - Rituximab, plasma exchange and intravenous immunoglobulins as a new treatment
      strategy for severe HLA alloimmune platelet refractoriness.
AB  - Platelet refractoriness (PR) due to HLA alloimmunization is a common and serious
      complication of patients receiving long-term packed red blood cell and platelet
      transfusions. Although most alloimmunized patients will respond to HLA-matched
      platelets, 20-50% of patients will remain refractory even to matched platelets.
      Several measures have been reported to overcome this complication, such as
      intravenous immunoglobulins (IVIG), plasma exchange (PE), protein A column
      therapy, or rituximab. We report a woman with acute myeloid leukemia secondary to
      myelodysplastic syndrome who was diagnosed with PR because of HLA
      alloimmunization. Due to difficulties in finding HLA-compatible platelet donors
      by cross-reactive groups in our panel of HLA-typed platelet donors, the patient
      received treatment with rituximab, PEs and IVIG. With this treatment strategy,
      the presence of HLA antibodies decreased from a panel-reactive antibody (PRA) of
      89-0%. This allowed the performance of hematopoietic progenitor cell
      transplantation with random donor platelets. Rituximab, PE, and IVIG may be an
      option to overcome severe PR due to poly-specific HLA alloimmunization.

PMID- 24867636
TI  - Ki-67 is a PP1-interacting protein that organises the mitotic chromosome
      periphery.
AB  - When the nucleolus disassembles during open mitosis, many nucleolar proteins and
      RNAs associate with chromosomes, establishing a perichromosomal compartment
      coating the chromosome periphery. At present nothing is known about the function
      of this poorly characterised compartment. In this study, we report that the
      nucleolar protein Ki-67 is required for the assembly of the perichromosomal
      compartment in human cells. Ki-67 is a cell-cycle regulated protein phosphatase 1
      binding protein that is involved in phospho-regulation of the nucleolar protein
      B23/nucleophosmin. Following siRNA depletion of Ki-67, NIFK, B23, nucleolin, and
      four novel chromosome periphery proteins all fail to associate with the periphery
      of human chromosomes. Correlative light and electron microscopy (CLEM) images
      suggest a near-complete loss of the entire perichromosomal compartment. Mitotic
      chromosome condensation and intrinsic structure appear normal in the absence of
      the perichromosomal compartment but significant differences in nucleolar
      reassembly and nuclear organisation are observed in post-mitotic cells.DOI:
      http://dx.doi.org/10.7554/eLife.01641.001. 

PMID- 24867637
TI  - Global analysis of p53-regulated transcription identifies its direct targets and
      unexpected regulatory mechanisms.
AB  - The p53 transcription factor is a potent suppressor of tumor growth. We report
      here an analysis of its direct transcriptional program using Global Run-On
      sequencing (GRO-seq). Shortly after MDM2 inhibition by Nutlin-3, low levels of
      p53 rapidly activate ~200 genes, most of them not previously established as
      direct targets. This immediate response involves all canonical p53 effector
      pathways, including apoptosis. Comparative global analysis of RNA synthesis vs
      steady state levels revealed that microarray profiling fails to identify low
      abundance transcripts directly activated by p53. Interestingly, p53 represses a
      subset of its activation targets before MDM2 inhibition. GRO-seq uncovered a
      plethora of gene-specific regulatory features affecting key survival and
      apoptotic genes within the p53 network. p53 regulates hundreds of enhancer
      derived RNAs. Strikingly, direct p53 targets harbor pre-activated enhancers
      highly transcribed in p53 null cells. Altogether, these results enable the study
      of many uncharacterized p53 target genes and unexpected regulatory
      mechanisms.DOI: http://dx.doi.org/10.7554/eLife.02200.001. 

PMID- 24867638
TI  - Hsp70 chaperones are non-equilibrium machines that achieve ultra-affinity by
      energy consumption.
AB  - 70-kDa Heat shock proteins are ATP-driven molecular chaperones that perform a
      myriad of essential cellular tasks. Although structural and biochemical studies
      have shed some light on their functional mechanism, the fundamental issue of the
      role of energy consumption, due to ATP-hydrolysis, has remained unaddressed. Here
      we establish a clear connection between the non-equilibrium nature of Hsp70, due
      to ATP hydrolysis, and the determining feature of its function, namely its high
      affinity for its substrates. Energy consumption can indeed decrease the
      dissociation constant of the chaperone-substrate complex by several orders of
      magnitude with respect to an equilibrium scenario. We find that the biochemical
      requirements for observing such ultra-affinity coincide with the physiological
      conditions in the cell. Our results rationalize several experimental observations
      and pave the way for further analysis of non-equilibrium effects underlying
      chaperone functions.DOI: http://dx.doi.org/10.7554/eLife.02218.001. 

PMID- 24867639
TI  - Hidden shift of the ionome of plants exposed to elevated CO2depletes minerals at
      the base of human nutrition.
AB  - Mineral malnutrition stemming from undiversified plant-based diets is a top
      global challenge. In C3 plants (e.g., rice, wheat), elevated concentrations of
      atmospheric carbon dioxide (eCO2) reduce protein and nitrogen concentrations, and
      can increase the total non-structural carbohydrates (TNC; mainly starch, sugars).
      However, contradictory findings have obscured the effect of eCO2 on the ionome
      the mineral and trace-element composition-of plants. Consequently, CO2-induced
      shifts in plant quality have been ignored in the estimation of the impact of
      global change on humans. This study shows that eCO2 reduces the overall mineral
      concentrations (-8%, 95% confidence interval: -9.1 to -6.9, p<0.00001) and
      increases TNC:minerals > carbon:minerals in C3 plants. The meta-analysis of 7761
      observations, including 2264 observations at state of the art FACE centers,
      covers 130 species/cultivars. The attained statistical power reveals that the
      shift is systemic and global. Its potential to exacerbate the prevalence of
      'hidden hunger' and obesity is discussed.DOI:
      http://dx.doi.org/10.7554/eLife.02245.001. 

PMID- 24867640
TI  - Rheotaxis facilitates upstream navigation of mammalian sperm cells.
AB  - A major puzzle in biology is how mammalian sperm maintain the correct swimming
      direction during various phases of the sexual reproduction process. Whilst
      chemotaxis may dominate near the ovum, it is unclear which cues guide spermatozoa
      on their long journey towards the egg. Hypothesized mechanisms range from
      peristaltic pumping to temperature sensing and response to fluid flow variations
      (rheotaxis), but little is known quantitatively about them. We report the first
      quantitative study of mammalian sperm rheotaxis, using microfluidic devices to
      investigate systematically swimming of human and bull sperm over a range of
      physiologically relevant shear rates and viscosities. Our measurements show that
      the interplay of fluid shear, steric surface-interactions, and chirality of the
      flagellar beat leads to stable upstream spiralling motion of sperm cells, thus
      providing a generic and robust rectification mechanism to support mammalian
      fertilisation. A minimal mathematical model is presented that accounts
      quantitatively for the experimental observations.DOI:
      http://dx.doi.org/10.7554/eLife.02403.001. 

PMID- 24867641
TI  - Distinct and separable roles for EZH2 in neurogenic astroglia.
AB  - The epigenetic mechanisms that enable specialized astrocytes to retain neurogenic
      competence throughout adult life are still poorly understood. Here we show that
      astrocytes that serve as neural stem cells (NSCs) in the adult mouse
      subventricular zone (SVZ) express the histone methyltransferase EZH2. This
      Polycomb repressive factor is required for neurogenesis independent of its role
      in SVZ NSC proliferation, as Ink4a/Arf-deficiency in Ezh2-deleted SVZ NSCs
      rescues cell proliferation, but neurogenesis remains defective. Olig2 is a direct
      target of EZH2, and repression of this bHLH transcription factor is critical for
      neuronal differentiation. Furthermore, Ezh2 prevents the inappropriate activation
      of genes associated with non-SVZ neuronal subtypes. In the human brain, SVZ cells
      including local astroglia also express EZH2, correlating with postnatal
      neurogenesis. Thus, EZH2 is an epigenetic regulator that distinguishes neurogenic
      SVZ astrocytes, orchestrating distinct and separable aspects of adult stem cell
      biology, which has important implications for regenerative medicine and
      oncogenesis.DOI: http://dx.doi.org/10.7554/eLife.02439.001. 

PMID- 24867642
TI  - MicroRNAs shape circadian hepatic gene expression on a transcriptome-wide scale.
AB  - A considerable proportion of mammalian gene expression undergoes circadian
      oscillations. Post-transcriptional mechanisms likely make important contributions
      to mRNA abundance rhythms. We have investigated how microRNAs (miRNAs) contribute
      to core clock and clock-controlled gene expression using mice in which miRNA
      biogenesis can be inactivated in the liver. While the hepatic core clock was
      surprisingly resilient to miRNA loss, whole transcriptome sequencing uncovered
      widespread effects on clock output gene expression. Cyclic transcription paired
      with miRNA-mediated regulation was thus identified as a frequent phenomenon that
      affected up to 30% of the rhythmic transcriptome and served to post
      transcriptionally adjust the phases and amplitudes of rhythmic mRNA accumulation.
      However, only few mRNA rhythms were actually generated by miRNAs. Overall, our
      study suggests that miRNAs function to adapt clock-driven gene expression to
      tissue-specific requirements. Finally, we pinpoint several miRNAs predicted to
      act as modulators of rhythmic transcripts, and identify rhythmic pathways
      particularly prone to miRNA regulation.DOI:
      http://dx.doi.org/10.7554/eLife.02510.001. 

PMID- 24867645
TI  - Finding the missing link.
AB  - The discovery of an ancient protein complex reveals the evolutionary
      relationships between the proteins that help to form vesicles. 

PMID- 24867646
TI  - Synthesis of multi-substituted vinylsilanes via copper(I)-catalyzed
      hydrosilylation reactions of allenes and propiolate derivatives with
      silylboronates.
AB  - An efficient and general copper(I)-catalyzed method for the synthesis of multi
      substituted vinylsilanes is reported. Multi-substituted allenes with electron
      withdrawing groups and propiolate derivatives reacted well with
      (dimethylphenylsilyl)boronic acid pinacol ester to afford silyl-substituted
      butenoate derivatives and beta-silyl-substituted acrylate derivatives,
      respectively. The corresponding products could be obtained in moderate to high
      yields and with good to excellent stereoselectivities.

PMID- 24867643
TI  - Molecular mechanism of Aurora A kinase autophosphorylation and its allosteric
      activation by TPX2.
AB  - We elucidate the molecular mechanisms of two distinct activation strategies
      (autophosphorylation and TPX2-mediated activation) in human Aurora A kinase.
      Classic allosteric activation is in play where either activation loop
      phosphorylation or TPX2 binding to a conserved hydrophobic groove shifts the
      equilibrium far towards the active conformation. We resolve the controversy about
      the mechanism of autophosphorylation by demonstrating intermolecular
      autophosphorylation in a long-lived dimer by combining X-ray crystallography with
      functional assays. We then address the allosteric activation by TPX2 through
      activity assays and the crystal structure of a domain-swapped dimer of
      dephosphorylated Aurora A and TPX2(1-25). While autophosphorylation is the key
      regulatory mechanism in the centrosomes in the early stages of mitosis,
      allosteric activation by TPX2 of dephosphorylated Aurora A could be at play in
      the spindle microtubules. The mechanistic insights into autophosphorylation and
      allosteric activation by TPX2 binding proposed here, may have implications for
      understanding regulation of other protein kinases.DOI:
      http://dx.doi.org/10.7554/eLife.02667.001. 

PMID- 24867644
TI  - Characterization of TSET, an ancient and widespread membrane trafficking complex.
AB  - The heterotetrameric AP and F-COPI complexes help to define the cellular map of
      modern eukaryotes. To search for related machinery, we developed a structure
      based bioinformatics tool, and identified the core subunits of TSET, a 'missing
      link' between the APs and COPI. Studies in Dictyostelium indicate that TSET is a
      heterohexamer, with two associated scaffolding proteins. TSET is non-essential in
      Dictyostelium, but may act in plasma membrane turnover, and is essentially
      identical to the recently described TPLATE complex, TPC. However, whereas TPC was
      reported to be plant-specific, we can identify a full or partial complex in every
      eukaryotic supergroup. An evolutionary path can be deduced from the earliest
      origins of the heterotetramer/scaffold coat to its multiple manifestations in
      modern organisms, including the mammalian muniscins, descendants of the TSET
      medium subunits. Thus, we have uncovered the machinery for an ancient and
      widespread pathway, which provides new insights into early eukaryotic
      evolution.DOI: http://dx.doi.org/10.7554/eLife.02866.001. 

PMID- 24867647
TI  - Model to predict the survival benefit of radiation for patients with
      rhabdomyosarcoma after surgery: a population-based study.
AB  - The aim of this study was to build a model to predict the survival benefit of
      radiotherapy for resected rhabdomyo-sarcoma at the individual level, to help
      clinicians and their patients make more informed decisions about adjuvant
      radiotherapy. Patients with resection of rhabdomyosarcoma between 1990 and 2010
      were derived from the Surveillance, Epidemiology and End Results database. A
      multivariate Cox proportional hazard model was built to model cause-specific
      survival. We used inverse-probability weighting with propensity scores to
      minimize selection bias in the observation study. The Akaike information
      criterion technique was used to reduce variables in the model. Nomograms were
      created with the reduced model after model selection. The study cohort comprised
      1578 patients. The 5-year cause-specific survival rate was 64.3% (95% confidence
      interval (CI) 61.7-66.9%) and the 10-year cause-specific survival rate was 61.4%
      (95% CI, 58.7-64.2%) for the entire cohort. Five-year cause-specific survival
      rates were 62.3% (95% CI, 58.6-66.2%) and 66.1% (95% CI, 62.6-69.8%) for patients
      with surgery alone and adjuvant radiotherapy, respectively (P<0.01). Age, size,
      histological type, tumor stage, positive regional nodes and adjuvant radiotherapy
      were retained in the reduced model. Model performance was good, with a c-index of
      0.78 (95% CI, 0.76-0.80). This clinical predictive tool can quantify the benefit
      of adjuvant radiotherapy after resection of rhabdomyosarcoma, and provide
      patients and clinicians with assistance in treatment selection.

PMID- 24867648
TI  - Association of growth differentiation factor 15 (GDF15) polymorphisms with serum
      GDF15 and ferritin levels in beta-thalassemia.

PMID- 24867649
TI  - Cleft lip-cleft palate in Zimbabwe: estimating the distribution of the surgical
      burden of disease using geographic information systems.
AB  - OBJECTIVES/HYPOTHESIS: To evaluate the prevalence and unmet need for cleft lip
      cleft palate reconstructive surgery by using incidence. Our hypotheses were that
      the age of presentation to screening clinics will decrease between 2006 and 2012,
      and the geospatial distribution of cases will expand to a more rural catchment
      area. STUDY DESIGN: Longitudinal cross-sectional/geospatial distribution study.
      METHODS: An online, secure database was created from intake forms for children
      with cleft lip-cleft palate (N=604) in Zimbabwe (2006-2012). Univariate analysis
      was completed. A linear regression model was fitted to test the time trend of a
      child's age at the time of presentation. Unique patient addresses (n=411) were
      matched. Maps presenting cleft diagnosis and presentation year were created with
      geographic information systems (GIS) software. RESULTS: The median age of
      presentation was greater for isolated cleft palate (4.2 years, n=106) than
      isolated cleft lip (1.5 years, n=251) and cleft lip-cleft palate (2.0 years,
      n=175). Cleft lip cases were mostly left sided with equal gender distribution.
      The overall age of presentation remained stable (P=.83). The age of children with
      isolated cleft palate decreased by 0.8 years per surgical trip (P=.01),
      suggesting the prevalence of unrepaired cleft palate is decreasing due to local
      and visiting surgeons. The catchment area extended to a less populous area, but
      clustered around Harare and Bulawayo. CONCLUSIONS: This study gives Zimbabwe
      specific evidence that supports reports of the persistent burden of disease
      requiring attention. The GIS software provided data for the primary needs
      assessment, which will direct communication to healthcare providers and
      prospective patients outside of the current catchment area. LEVEL OF EVIDENCE: 3

PMID- 24867650
TI  - iHWG-MUNIR: a miniaturised near-infrared gas sensor based on substrate-integrated
      hollow waveguides coupled to a micro-NIR-spectrophotometer.
AB  - A miniaturised gas analyser is described and evaluated based on the use of a
      substrate-integrated hollow waveguide (iHWG) coupled to a microsized near
      infrared spectrophotometer comprising a linear variable filter and an array of
      InGaAs detectors. This gas sensing system was applied to analyse surrogate
      samples of natural fuel gas containing methane, ethane, propane and butane,
      quantified by using multivariate regression models based on partial least square
      (PLS) algorithms and Savitzky-Golay 1(st) derivative data preprocessing. The
      external validation of the obtained models reveals root mean square errors of
      prediction of 0.37, 0.36, 0.67 and 0.37% (v/v), for methane, ethane, propane and
      butane, respectively. The developed sensing system provides particularly rapid
      response times upon composition changes of the gaseous sample (approximately 2 s)
      due the minute volume of the iHWG-based measurement cell. The sensing system
      developed in this study is fully portable with a hand-held sized analyser
      footprint, and thus ideally suited for field analysis. Last but not least, the
      obtained results corroborate the potential of NIR-iHWG analysers for monitoring
      the quality of natural gas and petrochemical gaseous products. 

PMID- 24867652
TI  - Rituximab treatment for fibrillary glomerulonephritis.
AB  - BACKGROUND: Approximately 50% of patients with fibrillary glomerulonephritis (GN)
      progress to end-stage renal disease (ESRD) within 2 years of diagnosis, and no
      standard therapy exists. The data on rituximab therapy for fibrillary GN are
      limited and have inconsistent outcomes. Here, we report the largest case series
      to date using rituximab for fibrillary GN. METHODS: Retrospective chart reviews
      were conducted on 12 patients with fibrillary GN who were treated with rituximab
      (1 g i.v. * 2 doses or 375 mg/m(2) * 4 doses) at the Center for Glomerular
      Diseases at Columbia University Medical Center. Non-progression of disease was
      defined as stable/improved serum creatinine (SCr) with a minimum of 1 year of
      follow-up. RESULTS: The median SCr was 2.1 (range 0.7-2.7) mg/dL, median
      estimated glomerular filtration rate (eGFR) 39 (range 21-98) mL/min/1.73 m(2) and
      median proteinuria 4497 (range 210-7542) mg/day at the time of rituximab
      initiation. Four patients had received immunosuppression before rituximab, and
      nine received immunosuppression after rituximab, with four receiving a second
      rituximab course. Four of 12 patients were non-progressors, 3 of 12 had
      progressive renal dysfunction without reaching ESRD, and 5 patients reached ESRD.
      The median follow-up for patients who did not reach ESRD was 38 (range 14-76)
      months after rituximab treatment. Non-progressors had lower SCr values, higher
      eGFRs and shorter median duration from diagnosis to treatment than progressors.
      No serious adverse events were noted. CONCLUSIONS: Rituximab therapy was
      associated with non-progression of renal disease in 4 of 12 patients. At the time
      of treatment, these non-progressors had better renal function and shorter time
      from diagnosis to treatment than progressors.

PMID- 24867653
TI  - Clinical microbiology laboratory: from the Pasteur model to the 24/7 clinical
      chemistry concept.

PMID- 24867654
TI  - Influence of clinically significant portal hypertension on surgical outcomes and
      survival following hepatectomy for hepatocellular carcinoma: a systematic review
      and meta-analysis.
AB  - Surgical resection is not indicated in patients with portal hypertension in the
      current guideline of Barcelona Clinic Liver Cancer (BCLC) stage. We report a
      systematic review and meta-analysis to determine the impact of clinically
      significant portal hypertension on survival in patients with hepatocellular
      carcinoma (HCC) following hepatectomy. Searched data in PubMed, EMBASE, and the
      Cochrane Library were reviewed and 11 publications were included in the meta
      analysis. The inclusion criteria of clinically significant portal hypertension
      were esophageal varices and/or thrombocytopenia with splenomegaly. Pooled data
      were extracted and computed into odds ratios (ORs) for clinical outcome and
      hazard ratios (HRs) for overall survival. The final pooled data were composed of
      2,285 patients. There were 775 patients with clinically significant portal
      hypertension (PHT group) and 1,510 patients without clinically significant portal
      hypertension (non-PHT group). Pooled proportion of mortality was 6.1% (95%
      confidence interval [CI] 0.032-0.116) in PHT group and 2.8% (95% CI 0.014-0.054)
      in the non-PHT group. The pooled proportion of morbidity was 41.7% (95% CI 0.274
      0.575) in PHT group and 34.7% (95% CI 0.243-0.467) in non-PHT group. Pooled data
      confirmed a significantly higher postoperative mortality in the PHT group, with
      OR 3.02 (P < 0.001). The PHT group also demonstrated significantly higher
      occurrence of postoperative complications (OR 1.39, P = 0.008), liver-related
      morbidity (OR 3.10, P < 0.00001), and liver failure (OR 2.14, P = 0.0005)
      compared to the non-PHT group. According to the overall survival, pooled analysis
      demonstrated that the PHT group demonstrated poorer survival than the non-PHT
      group (HR 1.48, P = 0.007). The analyses support significantly higher rates of
      postoperative mortality, complications, liver-related morbidity, liver failure,
      and poorer overall survival in PHT group compared with the non-PHT group.
      Surgical resection should be selected carefully with strict surgical strategy in
      patients with clinically significant portal hypertension when surgical resection
      is planned. 

PMID- 24867655
TI  - [A 26-year old with multiple plaques on face, torso, and extremities].

PMID- 24867656
TI  - Associations of the Baltic Sea diet with cardiometabolic risk factors--a meta
      analysis of three Finnish studies.
AB  - Dyslipidaemia, hypertension and low-grade inflammation increase the risk of CVD.
      In the present meta-analysis, we examined whether adherence to a healthy Nordic
      diet, also called the Baltic Sea diet, may associate with a lower risk of these
      cardiometabolic risk factors. In 2001-2007, three cross-sectional Finnish studies
      were conducted: the Dietary, Lifestyle and Genetic Determinants of Obesity and
      Metabolic Syndrome study (n 4776); Health 2000 Survey (n 5180); Helsinki Birth
      Cohort Study (n 1972). The following parameters were assessed in these three
      studies: blood pressure, total, HDL- and LDL-cholesterol, TAG and high
      sensitivity C-reactive protein (hs-CRP); a validated FFQ was used to assess the
      participants' dietary intakes. The Baltic Sea Diet Score (BSDS) was developed
      based on the healthy Nordic diet. All studies assessed confounding variables,
      such as physical activity and BMI, based on standardised questionnaires and
      measurements. The random-effects meta-analysis provided summary estimates for OR
      and 95 % CI by the BSDS quintiles. In the meta-analysis, the risk of elevated hs
      CRP concentration was lower among men (OR 0.58, 95 % CI 0.43, 0.78) and women (OR
      0.73, 95 % CI 0.58, 0.91) in the highest BSDS quintile than among those in the
      lowest BSDS quintile. In contrast, the risk of lowered HDL-cholesterol
      concentration was higher among women (OR 1.67, 95 % CI 1.12, 2.48) in the highest
      BSDS quintile than among those in the lowest BSDS quintile. However, no other
      associations were found. In conclusion, the associations between the adherence to
      the healthy Nordic diet and cardiometabolic risk factors are equivocal.
      Longitudinal studies are needed to further examine this hypothesis.

PMID- 24867657
TI  - Urine as a material for evaluation of exposure to manganese in methcathinone
      users.
AB  - Chronic exposure even to low doses of manganese may lead to development of
      neurological syndrome similar to parkinsonism. The aim of this research is to
      assess the possibility of manganese poisoning based on the level of metal in the
      urine of long-term methcathinone users from Poland. Graphite furnace atomic
      absorption spectroscopy (GFAAS) was used to determine manganese in urine, while
      the detection of the psychoactive drugs was performed by high-performance liquid
      chromatography (HPLC). Results of survey on longitudinal patterns of drug use
      showed that users of traditional illicit drugs now turn to cheaper alternatives,
      such as methcathinone. Parkinsonian features were observed in almost half of
      methcathinone users. The subjects had a higher mean level of Mn in their urine
      (8.68+/-9.27 MUg L(-1)) than the controls (4.27+/-1.91 MUg L(-1)). The presence
      of numerous psychoactive substances (in unchanged forms and their metabolites)
      was confirmed in all of the samples, with only one exception. The elevated level
      of manganese in urine (in 29.2% of patients) can be used as a primary marker of
      recent methcathinone administration, especially in the case of long time
      intravenous drug users where blood sampling is complicated.

PMID- 24867662
TI  - Dipeptidyl peptidase-4 inhibitors can minimize the hypoglycaemic burden and
      enhance safety in elderly people with diabetes.
AB  - The prevalence of type 2 diabetes mellitus (T2DM) among elderly people is
      increasing. Often associated with disabilities/comorbidities, T2DM lowers the
      chances of successful aging and is independently associated with frailty and an
      increased risk of hypoglycaemia, which can be further exacerbated by
      antihyperglycaemic treatment. From this perspective, the clinical management of
      T2DM in the elderly is challenging and requires individualization of optimum
      glycaemic targets depending on comorbidities, cognitive functioning and ability
      to recognize and self-manage the disease. The lack of solid evidence-based
      medicine supporting treatment guidelines for older people with diabetes further
      complicates the matter. Several classes of medicine for the treatment of T2DM are
      currently available and different drug combinations are often required to achieve
      individualized glycaemic goals. Many of these drugs, however, carry disadvantages
      such as the propensity to cause weight gain or hypoglycaemia. Dipeptidyl
      peptidase-4 (DPP-4) inhibitors, a recent addition to the pharmacological
      armamentarium, have become widely accepted in clinical practice because of their
      efficacy, low risk of hypoglycaemia, neutral effect on body weight, and
      apparently greater safety in patients with kidney failure. Although more
      information is needed to reach definitive conclusions, growing evidence suggests
      that DPP-4 inhibitors may become a valuable component in the pharmacological
      management of elderly people with T2DM. The present review aims to delineate the
      potential advantages of this pharmacological approach in the treatment of elderly
      people with T2DM. 

PMID- 24867666
TI  - Cognitive-behavioral therapy for panic disorder with agoraphobia in older people:
      a comparison with younger patients.
AB  - BACKGROUND: Older adults with panic disorder and agoraphobia (PDA) are
      underdiagnosed and undertreated, while studies of cognitive-behavioral therapy
      (CBT) are lacking. This study compares the effectiveness of CBT for PDA in
      younger and older adults. METHODS: A total of 172 patients with PDA (DSM-IV)
      received manualized CBT. Primary outcome measures were avoidance behavior
      (Mobility Inventory Avoidance scale) and agoraphobic cognitions (Agoraphobic
      Cognitions Questionnaire), with values of the younger (18-60 years) and older (>=
      60 years) patients being compared using mixed linear models adjusted for baseline
      inequalities, and predictive effects of chronological age, age at PDA onset and
      duration of illness (DOI) being examined using multiple linear regressions.
      RESULTS: Attrition rates were 2/31 (6%) for the over-60s and 31/141 (22%) for the
      under-60s group (chi(2) = 3.43, df = 1, P = .06). Patients in both age groups
      improved on all outcome measures with moderate-to-large effect sizes. Avoidance
      behavior had improved significantly more in the 60+ group (F = 4.52, df = 1,134,
      P = .035), with agoraphobic cognitions showing no age-related differences.
      Baseline severity of agoraphobic avoidance and agoraphobic cognitions were the
      most salient predictors of outcome (range standardized betas 0.59 through 0.76,
      all P-values < .001). Apart from a superior reduction of agoraphobic avoidance in
      the 60+ participants (beta = -0.30, P = .037), chronological age was not related
      to outcome, while in the older patients higher chronological age, late-onset type
      and short DOI were linked to superior improvement of agoraphobic avoidance.
      CONCLUSIONS: CBT appears feasible for 60+ PDA-patients, yielding outcomes that
      are similar and sometimes even superior to those obtained in younger patients.

PMID- 24867667
TI  - Losing the left side of the world: rightward shift in human spatial attention
      with sleep onset.
AB  - Unilateral brain damage can lead to a striking deficit in awareness of stimuli on
      one side of space called Spatial Neglect. Patient studies show that neglect of
      the left is markedly more persistent than of the right and that its severity
      increases under states of low alertness. There have been suggestions that this
      alertness-spatial awareness link may be detectable in the general population.
      Here, healthy human volunteers performed an auditory spatial localisation task
      whilst transitioning in and out of sleep. We show, using independent
      electroencephalographic measures, that normal drowsiness is linked with a
      remarkable unidirectional tendency to mislocate left-sided stimuli to the right.
      The effect may form a useful healthy model of neglect and help in understanding
      why leftward inattention is disproportionately persistent after brain injury. The
      results also cast light on marked changes in conscious experience before full
      sleep onset. 

PMID- 24867668
TI  - A rare cause of intussusception in the adult: intestinal bezoar.

PMID- 24867672
TI  - Can one evaluate bone disease in chronic kidney disease without a biopsy?
AB  - PURPOSE OF REVIEW: Chronic kidney disease-mineral and bone disorder (CKD-MBD) is
      a complex disorder of bone and mineral metabolism that results in an excess risk
      of fractures, cardiovascular events and mortality. The management of the bone
      disorder aspect of CKD-MBD may require bone biopsy to determine appropriate
      treatment strategies. However, it is unclear when biopsy may be necessary and
      whether or not state-of-the art imaging and serologic testing can supplant the
      bone biopsy as a tool to assist with management decisions. RECENT FINDINGS:
      Advances in imaging methods now permit the noninvasive assessment of structural
      aspects of bone quality. Furthermore, common bone imaging tools, such as dual
      energy X-ray absorptiometry, can be used to stratify for fracture risk.
      Circulating markers of bone turnover can be used to assess the risk of bone loss
      and fracture, but they are less useful in diagnosing the type of renal
      osteodystrophy. SUMMARY: Although advances in imaging now permit the assessment
      of fracture risk more accurately in CKD patients, the assessment of the type of
      renal osteodystrophy remains poor without bone biopsy. The virtual bone biopsy
      will be possible only when we are able to noninvasively assess turnover with good
      accuracy. A bone biopsy is needed when the bone turnover is unclear.

PMID- 24867671
TI  - Recent technical developments in the study of ER-associated degradation.
AB  - Endoplasmic reticulum-associated degradation (ERAD) is a mechanism during which
      native and misfolded proteins are recognized and retrotranslocated across the ER
      membrane to the cytosol for degradation by the ubiquitin-proteasome system. Like
      other cellular pathways, the factors required for ERAD have been analyzed using
      both conventional genetic and biochemical approaches. More recently, however, an
      integrated top-down approach has identified a functional network that underlies
      the ERAD system. In turn, bottom-up reconstitution has become increasingly
      sophisticated and elucidated the molecular mechanisms underlying substrate
      recognition, ubiquitylation, retrotranslocation, and degradation. In addition, a
      live cell imaging technique and a site-specific in vivo photo-crosslinking
      approach have further dissected specific steps during ERAD. These technical
      developments have revealed an unexpected dynamicity of the membrane-associated
      ERAD complex. In this article, we will discuss how these technical developments
      have improved our understanding of the ERAD pathway and have led to new
      questions. 

PMID- 24867674
TI  - Advances in slit diaphragm signaling.
AB  - PURPOSE OF REVIEW: The podocyte slit diaphragm is a fundamental component of the
      glomerular filtration barrier and its function is highly dependent on the
      maintenance of specialized actin-based projections known as foot processes. In
      this review, we update the function of key slit diaphragm-associated proteins,
      and introduce some new players and emerging avenues of research within podocyte
      biology. RECENT FINDINGS: Studies using rodent models continue to support the
      long-held belief that precise regulation of actin dynamics at the slit diaphragm
      is essential for proper foot process organization. However, it is also becoming
      increasingly clear that alterations in actin remodeling can significantly
      contribute to damage in both animal models and human disease. In particular, the
      importance of signaling via the Rho family of GTPases has been recognized, as
      well as the requirement for proper localization and turnover of the slit
      diaphragm. SUMMARY: Regulation of the connection between the slit diaphragm and
      the podocyte actin network requires complex interplay between multiple signaling
      pathways. New discoveries contribute to an ever-expanding view of the slit
      diaphragm and serve to create a framework for the development of new therapeutic
      strategies targeting podocyte function in the future.

PMID- 24867673
TI  - New functional aspects of the extracellular calcium-sensing receptor.
AB  - PURPOSE OF REVIEW: Variations in extracellular calcium level have a large impact
      on kidney function. Most of the effects seen are attributed to the calcium
      sensing receptor (CaSR), a widely expressed G-protein-coupled cell surface
      protein with an important function in bone mineral homeostasis. The purpose of
      this review is to recapitulate the novel functional aspects of CaSR. RECENT
      FINDINGS: Results from mouse models demonstrate important functions for CaSR in
      various tissues. In the kidney, the main role of CaSR is the regulation of
      calcium reabsorption in the thick ascending limb, independently of its role on
      parathyroid hormone secretion. CaSR modulates claudin 14, the gatekeeper of
      paracellular ion transport in the thick ascending limb that is associated with
      urinary calcium excretion. One intracellular signaling pathway by which CaSR
      alters tight junction permeability is the calcineurin-NFAT1c-microRNA-claudin14
      axis. SUMMARY: The main function of CaSR in the kidney is the regulation of
      calcium excretion in the thick ascending limb, independently of parathyroid
      hormone. CaSR modulates paracellular cation transport by altering expression of
      the tight junction protein claudin 14. Still more work is needed to fully
      understand all functions of CaSR in the kidney. Alternative pathways of calcium
      'sensing' in the kidney need to be investigated.

PMID- 24867675
TI  - Coupling fibroblast growth factor 23 production and cleavage: iron deficiency,
      rickets, and kidney disease.
AB  - PURPOSE OF REVIEW: High levels of fibroblast growth factor 23 (FGF23) cause the
      rare disorders of hypophosphatemic rickets and are a risk factor for
      cardiovascular disease and death in patients with chronic kidney disease (CKD).
      Despite major advances in understanding FGF23 biology, fundamental aspects of
      FGF23 regulation in health and in CKD remain mostly unknown. RECENT FINDINGS:
      Autosomal dominant hypophosphatemic rickets (ADHR) is caused by gain-of-function
      mutations in FGF23 that prevent its proteolytic cleavage, but affected
      individuals experience a waxing and waning course of phosphate wasting. This led
      to the discovery that iron deficiency is an environmental trigger that stimulates
      FGF23 expression and hypophosphatemia in ADHR. Unlike osteocytes in ADHR, normal
      osteocytes couple increased FGF23 production with commensurately increased FGF23
      cleavage to ensure that normal phosphate homeostasis is maintained in the event
      of iron deficiency. Simultaneous measurement of FGF23 by intact and C-terminal
      assays supported these breakthroughs by providing minimally invasive insight into
      FGF23 production and cleavage in bone. These findings also suggest a novel
      mechanism of FGF23 elevation in patients with CKD, who are often iron deficient
      and demonstrate increased FGF23 production and decreased FGF23 cleavage,
      consistent with an acquired state that mimics the molecular pathophysiology of
      ADHR. SUMMARY: Iron deficiency stimulates FGF23 production, but normal osteocytes
      couple increased FGF23 production with increased cleavage to maintain normal
      circulating levels of biologically active hormone. These findings uncover a
      second level of FGF23 regulation within osteocytes, failure of which culminates
      in elevated levels of biologically active FGF23 in ADHR and perhaps CKD.

PMID- 24867677
TI  - An estimation of the artisanal small-scale production of gold in the world.
AB  - The increase in gold price of over 400% between 2002 and 2012, due to a shift
      towards safe investments in a period of crisis in the global economy, created a
      rapid increase in gold production. A response to this shift in production was
      observed for artisanal and small-scale mining (ASM) units in remote locations of
      the world, but this phenomenon has not been quantified yet. The work presented
      here was done to provide a quantitative tool for estimation of the gold (Au)
      produced by ASM and the population of workers involved in the production process,
      and assessment of mercury (Hg) consumed. The following hypotheses were addressed:
      i) It is possible to estimate, on first approximation, the amount of Au
      production in the world by artisanal mining; ii) Au production by artisanal
      mining varies by country and continent and iii) Hg consumption due to ASM can be
      correlated with the methods applied in the different countries and continents for
      the production of Au. To do this we estimated the number of miners, calculated
      the change in Au price and production and then applied an adjustment factor to
      calculate Hg production by country and continent. The amount of Au produced
      depends on technology of the miners by continents (highest in South America,
      medium in Asia and Central America, and lowest in Africa), and the geologic
      setting (not investigated here). The results of the estimation show that, as of
      2011, over 16 million Artisanal Miners, in the world, were involved in gold
      extraction (mining or treatment), producing between 380 and 450 t of gold per
      year, with clear global behavior between the continents in terms of recovery
      efficiency, confirmed by data on Hg release that is higher in countries with
      lower technology.

PMID- 24867676
TI  - alphaKlotho and vascular calcification: an evolving paradigm.
AB  - PURPOSE OF REVIEW: Cardiovascular disease remains the single most serious
      contributor to mortality in chronic kidney disease (CKD). Although conventional
      risk factors are prevalent in CKD, both cardiomyopathy and vasculopathy can be
      caused by pathophysiologic mechanisms specific to the uremic state. CKD is a
      state of systemic alphaKlotho deficiency. Although the molecular mechanism of
      action of alphaKlotho is not well understood, the downstream targets and biologic
      functions of alphaKlotho are astonishingly pleiotropic. An emerging body of
      literature links alphaKlotho to uremic vasculopathy. RECENT FINDINGS: The
      expression of alphaKlotho in the vasculature is controversial because of
      conflicting data. Regardless of whether alphaKlotho acts as a circulating or
      resident protein, there are good data associating changes in alphaKlotho levels
      with vascular pathology including vascular calcification and in-vitro data of the
      direct action of alphaKlotho on both the endothelium and vascular smooth muscle
      cells in terms of cytoprotection and prevention of mineralization. SUMMARY: It is
      critical to understand the pathogenic role of alphaKlotho on the integral
      endothelium-vascular smooth muscle network rather than each cell type in
      isolation in uremic vasculopathy, as alphaKlotho can serve as a potential
      prognostic biomarker and a biological therapeutic agent.

PMID- 24867678
TI  - The influence of metamorphic grade on arsenic in metasedimentary bedrock
      aquifers: a case study from Western New England, USA.
AB  - Elevated As occurs in many meta-sedimentary bedrock aquifers where elevated bulk
      rock As content is one of the primary controls on the concentration of As in
      groundwater. This study was designed to determine As concentrations in a black
      shale, black slate and black phyllite sequence that comprises the bedrock aquifer
      system of the Taconic Mountain region of southwestern Vermont and adjacent New
      York State. Variability in groundwater As concentrations provides the impetus for
      this study: 25% of wells in weakly metamorphosed shales and slates (<lower
      chlorite zone) exceed 10 MUg/L (133 nmol/L) As, yet only 3% of wells in
      stratigraphically-equivalent phyllites (metamorphosed to >=upper chlorite zone)
      exceed 10 MUg/L As. Geochemical analysis indicates that whole-rock As content is
      inversely proportional to metamorphic grade, ranging from a mean of 26.9 mg kg(
      1) in low-grade black shales and slates to 13.8 mg kg(-1) in higher-grade black
      phyllites. The differences in As concentrations are statistically significant
      (p<0.03), and Cu, Ni, Pb and Zn are also significantly (p<0.03) depleted in
      higher-grade phyllites. These differences are attributed to recrystallization of
      pyrite with increasing metamorphic grade, a process which introduces As and other
      trace elements into pore fluids, after which the high mobility of As makes it
      susceptible to be leached out of metapelites. Data from this study and previous
      research indicates that depletion of As from metapelites tends to occur once the
      rocks reach upper chlorite zone or lower biotite zone, corresponding to
      metamorphic temperatures of ~250-350  degrees C. This suggests that, in the
      absence of subsequent hydrothermal mineralization (e.g. arsenopyrite in late
      stage veins), metapelites metamorphosed to upper chlorite zone or higher will be
      less likely to foster elevated As in groundwater compared to their lower-grade
      shale and slate counterparts.

PMID- 24867679
TI  - Green synthesis of silver nanoparticles using Eucalyptus leucoxylon leaves
      extract and evaluating the antioxidant activities of extract.
AB  - This study was designed to examine the in vitro antioxidant activity of essential
      oil and methanol extracts of Eucalyptus leucoxylon. Furthermore, the polar
      fraction of the extract was used as a reducing agent for the green synthesis of
      silver nanoparticles (Ag NPs). Antioxidant activities of the samples were
      determined by using three different test systems, namely DPPH and beta
      carotene/linoleic acid and reducing power. The structure and composition of the
      prepared Ag NPs were characterised by X-ray diffraction, scanning electron
      microscopy, transmission electron microscopy and UV-vis spectroscopy. Synthesised
      Ag NPs were almost spherical in shape with an average diameter of about ~ 50 nm
      and synthesised within 120 min reaction time at room temperature. 

PMID- 24867680
TI  - Glycan surface antigens from Bacillus anthracis as vaccine targets: current
      status and future perspectives.
AB  - Over recent years great attention has been directed to the discovery of novel
      antigens from Bacillus anthracis, because of the potential of its spores in the
      development of weapons for mass destruction. Substantial effort has been directed
      to the identification and immunochemical evaluation of glycans that might be used
      for specific diagnostic detection of the spores or immune-mediated prevention of
      anthrax. Carbohydrate structures found on surfaces of vegetative cells and spores
      are herein discussed. Among them, the cell wall polysaccharide and the
      tetrasaccharide unit isolated from the exosporium protein BclA were proven
      immunogenic in an animal model after covalent linkage to carrier protein. Further
      investigation is needed to fully assess the potential of these promising
      carbohydrate antigens for vaccine development. 

PMID- 24867681
TI  - Study of medication-free children with Tourette syndrome do not show imaging
      abnormalities.
AB  - BACKGROUND: Imaging studies of patients with Tourette's syndrome (TS) across
      different cohorts have shown alterations in gray and white matter in areas
      associated with the cortico-striato-thalamic-cortical (CSTC) pathways; however,
      no consistent findings have subsequently established a clear indication of the
      pathophysiology of TS. METHODS: This study was designed to investigate changes in
      gray and white matter in medication-free children with TS in the CSTC areas. With
      MRI, 24 children with TS and 18 healthy controls were analyzed using three
      complementary methods. RESULTS AND CONCLUSION: Analyses revealed no differences
      between controls and patients with TS in gray or white matter. Possible
      discrepancies between cohorts and methods may play a role in the different
      findings in other studies. Further studies investigating well-defined cohorts
      with TS analyzing both gray and white matter in the same cohort may add
      additional information to the pathophysiology of TS.

PMID- 24867683
TI  - Advances in genomic characterization of circulating tumor cells.
AB  - Molecular characterization of circulating tumor cells (CTCs) found in the blood
      of cancer patients offers the potential to provide new insights into the biology
      of cancer metastasis. However, since they are rare and difficult to isolate, the
      molecular nature of CTCs remains poorly understood. In this paper, we reviewed a
      decade's worth of scientific literature (2003-2013) describing efforts on
      isolation and genomic analysis of CTCs. The limited number of CTC genomic studies
      we found attested to the infancy of this field of study. These initial reports,
      however, provide an important framework for future comprehensive exploration of
      CTC biology. For CTCs to be broadly accepted as therapeutic targets and
      biomarkers of metastatic spread, further in-depth molecular characterization is
      warranted. 

PMID- 24867682
TI  - Functional link between muscarinic receptors and large-conductance Ca2+ 
      activated K+ channels in freshly isolated human detrusor smooth muscle cells.
AB  - Activation of muscarinic acetylcholine receptors (mAChRs) constitutes the primary
      mechanism for enhancing excitability and contractility of human detrusor smooth
      muscle (DSM). Since the large-conductance Ca(2+)-activated K(+) (KCa1.1) channels
      are key regulators of human DSM function, we investigated whether mAChR
      activation increases human DSM excitability by inhibiting KCa1.1 channels. We
      used the mAChR agonist, carbachol, to determine the changes in KCa1.1 channel
      activity upon mAChR activation in freshly isolated human DSM cells obtained from
      open bladder surgeries using the perforated whole cell and single KCa1.1 channel
      patch-clamp recordings. Human DSM cells were collected from 29 patients (23 males
      and 6 females, average age of 65.9 +/- 1.5 years). Carbachol inhibited the
      amplitude and frequency of KCa1.1 channel-mediated spontaneous transient outward
      currents and spontaneous transient hyperpolarizations, which are triggered by the
      release of Ca(2+) from ryanodine receptors. Carbachol also caused membrane
      potential depolarization, which was not observed in the presence of iberiotoxin,
      a KCa1.1 channel inhibitor, indicating the critical role of the KCa1.1 channels.
      The potential direct carbachol effects on KCa1.1 channels were examined under
      conditions of removing the major cellular Ca(2+) sources for KCa1.1 channel
      activation with pharmacological inhibitors (thapsigargin, ryanodine, and
      nifedipine). In the presence of these inhibitors, carbachol did not affect the
      single KCa1.1 channel open probability and mean KCa1.1 channel conductance (cell
      attached configuration) or depolarization-induced whole cell steady-state KCa1.1
      currents. The data support the concept that mAChR activation triggers indirect
      functional KCa1.1 channel inhibition mediated by intracellular Ca(2+), thus
      increasing the excitability in human DSM cells.

PMID- 24867684
TI  - Electrospun microcrimped fibers with nonlinear mechanical properties enhance
      ligament fibroblast phenotype.
AB  - Fiber structure and order greatly impact the mechanical behavior of fibrous
      materials. In biological tissues, the nonlinear mechanics of fibrous scaffolds
      contribute to the functionality of the material. The nonlinear mechanical
      properties of the wavy structure (crimp) in collagen allow tissue flexibility
      while preventing over-extension. A number of approaches have tried to recreate
      this complex mechanical functionality. We generated microcrimped fibers by
      briefly heating electrospun parallel fibers over the glass transition temperature
      or by ethanol treatment. The crimp structure is similar to those of collagen
      fibers found in native aorta, intestines, or ligaments. Using poly-L-lactic acid
      fibers, we demonstrated that the bulk materials exhibit changed stress-strain
      behaviors with a significant increase in the toe region in correlation to the
      degree of crimp, similar to those observed in collagenous tissues. In addition to
      mimicking the stress-strain behavior of biological tissues, the microcrimped
      fibers are instructive in cell morphology and promote ligament phenotypic gene
      expression. This effect can be further enhanced by dynamic tensile loading, a
      physiological perturbation in vivo. This rapid and economical approach for
      microcrimped fiber production provides an accessible platform to study structure
      function relationships and a novel functional scaffold for tissue engineering and
      cell mechanobiology studies. 

PMID- 24867685
TI  - A novel iron complex for highly efficient catalytic hydrogen generation from the
      hydrolysis of organosilanes.
AB  - Hydrolytic oxidation of organosilanes based on an iron catalyst is described for
      the first time. The novel iron complex, [Fe(C6H5N2O)(CO)(MeCN)3][PF6], exhibits
      excellent mediating power in the catalytic hydrolysis of organosilanes to produce
      dihydrogen and organosilanols with turnover numbers approaching 10(4) and
      turnover frequencies in excess of 10(2) min(-1) under ambient conditions. 

PMID- 24867687
TI  - Immunosuppression through constitutively activated NF-kappaB signalling in human
      ovarian cancer and its reversal by an NF-kappaB inhibitor.
AB  - BACKGROUND: Although T-cell immunity is thought to be involved in the prognosis
      of epithelial ovarian cancer (EOC) patients, immunosuppressive conditions hamper
      antitumour immune responses. Thus, their mechanisms and overcoming strategies
      need to be investigated. METHODS: The role of NF-kappaB in human EOC cells and
      macrophages was evaluated by in vitro production of immunosuppressive IL-6 and IL
      8 by EOC cells and in vivo analysis of immune responses in nude mice implanted
      with human EOC cells using an NF-kappaB inhibitor DHMEQ. RESULTS: In EOC
      patients, increased plasma IL-6, IL-8, and arginase were observed. The NF-kappaB
      inhibitor DHMEQ inhibited the production of IL-6 and IL-8 by EOC cell lines.
      Immunosuppression of human DCs and macrophages by culture supernatant of EOC
      cells was reversed with the pretreatment of DHMEQ. Administration of DHMEQ to
      nude mice implanted with human EOC resulted in the restoration of T-cell
      stimulatory activity of murine DCs along with the reduction of tumour
      accumulation and arginase expression of MDSCs. Nuclear factor-kappaB inhibition
      in tumour-bearing mice also enhanced antitumour effects of transferred murine
      naive T cells. CONCLUSIONS: NF-kappaB is involved in the immunosuppression
      induced by human EOC, and its inhibitor may restore antitumour immune responses,
      indicating that NF-kappaB is an attractive target for EOC treatment.

PMID- 24867689
TI  - Androgen metabolism in prostate cancer: from molecular mechanisms to clinical
      consequences.
AB  - Despite our most vigorous efforts, prostate cancer remains the second leading
      cause of cancer death in men. Understanding the intricacies of androgen
      metabolism is vital to finding therapeutic targets, particularly with progression
      of advanced prostate cancer after initial hormone therapy, where adrenal
      precursors are involved. Such is the case with castration-resistant prostate
      cancer, where adrenal androgens, for example, dehydroepiandrosterone, are a
      source for intratumoural synthesis of dihydrotestosterone. As prostate cancer
      progresses, androgen metabolism changes due to altered expression of
      steroidogenic enzymes and mutations in the components of the steroidogenic
      machinery. These alterations sustain disease and allow progression;
      mechanistically, they may also enable development of hormone therapy resistance.
      With the development of the newer agents, abiraterone acetate and enzalutamide,
      efforts have been made to better define the basis for response and resistance.
      This work can be carried out in cell lines, animal models, as well as with ex
      vivo analysis of tissues obtained from patients. Efforts to further elucidate the
      finer details of the steroidogenic pathway are necessary to move toward a
      curative paradigm for patients with localised disease at high risk for
      recurrence. 

PMID- 24867690
TI  - Assessing the function of homologous recombination DNA repair in malignant
      pleural effusion (MPE) samples.
AB  - BACKGROUND: Patients with malignant pleural effusions (MPEs) generally have
      advanced disease with poor survival and few therapeutic options. Cells within
      MPEs may be used to stratify patients for targeted therapy. Targeted therapy with
      poly(ADP ribose) polymerase inhibitors (PARPi) depends on identifying homologous
      recombination DNA repair (HRR)-defective cancer cells. We aimed to determine the
      feasibility of assaying HRR status in MPE cells. METHODS: A total of 15 MPE
      samples were collected from consenting patients with non-small-cell lung cancer
      (NSCLC), mesothelioma and ovarian and breast cancer. Primary cultures were
      confirmed as epithelial by pancytokeratin, and HRR status was determined by the
      detection of gammaH2AX and RAD51 foci following a 24-h exposure to rucaparib, by
      immunofluorescence microscopy. Massively parallel next-generation sequencing of
      DNA repair genes was performed on cultured MPE cells. RESULTS: From 15 MPE
      samples, 13 cultures were successfully established, with HRR function
      successfully determined in 12 cultures. Four samples - three NSCLC and one
      mesothelioma - were HRR defective and eight samples - one NSCLC, one
      mesothelioma, one sarcomatoid, one breast and four ovarian cancers - were HRR
      functional. No mutations in DNA repair genes were associated with HRR status, but
      there was probable loss of heterozygosity of FANCG, RPA1 and PARP1. CONCLUSIONS:
      HRR function can be successfully detected in MPE cells demonstrating the
      potential to stratify patients for targeted therapy with PARPi.

PMID- 24867688
TI  - Design and preliminary recruitment results of the Cluster randomised triAl of PSA
      testing for Prostate cancer (CAP).
AB  - BACKGROUND: Screening for prostate cancer continues to generate controversy
      because of concerns about over-diagnosis and unnecessary treatment. We describe
      the rationale, design and recruitment of the Cluster randomised triAl of PSA
      testing for Prostate cancer (CAP) trial, a UK-wide cluster randomised controlled
      trial investigating the effectiveness and cost-effectiveness of prostate-specific
      antigen (PSA) testing. METHODS: Seven hundred and eighty-five general
      practitioner (GP) practices in England and Wales were randomised to a population
      based PSA testing or standard care and then approached for consent to
      participate. In the intervention arm, men aged 50-69 years were invited to
      undergo PSA testing, and those diagnosed with localised prostate cancer were
      invited into a treatment trial. Control arm practices undertook standard UK
      management. All men were flagged with the Health and Social Care Information
      Centre for deaths and cancer registrations. The primary outcome is prostate
      cancer mortality at a median 10-year-follow-up. RESULTS: Among randomised
      practices, 271 (68%) in the intervention arm (198,114 men) and 302 (78%) in the
      control arm (221,929 men) consented to participate, meeting pre-specified power
      requirements. There was little evidence of differences between trial arms in
      measured baseline characteristics of the consenting GP practices (or men within
      those practices). CONCLUSIONS: The CAP trial successfully met its recruitment
      targets and will make an important contribution to international understanding of
      PSA-based prostate cancer screening.

PMID- 24867691
TI  - Connexins and cyclooxygenase-2 crosstalk in the expression of radiation-induced
      bystander effects.
AB  - BACKGROUND: Signalling events mediated by connexins and cyclooxygenase-2 (COX-2)
      have important roles in bystander effects induced by ionising radiation. However,
      whether these proteins mediate bystander effects independently or cooperatively
      has not been investigated. METHODS: Bystander normal human fibroblasts were
      cocultured with irradiated adenocarcinoma HeLa cells in which specific connexins
      (Cx) are expressed in the absence of endogenous Cx, before and after COX-2
      knockdown, to investigate DNA damage in bystander cells and their progeny.
      RESULTS: Inducible expression of gap junctions composed of connexin26 (Cx26) in
      irradiated HeLa cells enhanced the induction of micronuclei in bystander cells
      (P<0.01) and reduced the coculture time necessary for manifestation of the
      effect. In contrast, expression of connexin32 (Cx32) conferred protective
      effects. COX-2 knockdown in irradiated HeLa Cx26 cells attenuated the bystander
      response due to connexin expression. However, COX-2 knockdown resulted in
      enhanced micronucleus formation in the progeny of the bystander cells (P<0.001).
      COX-2 knockdown delayed junctional communication in HeLa Cx26 cells, and reduced,
      in the plasma membrane, the physical interaction of Cx26 with MAPKKK, a
      controller of the MAPK pathway that regulates COX-2 and connexin. CONCLUSIONS:
      Junctional communication and COX-2 cooperatively mediate the propagation of
      radiation-induced non-targeted effects. Characterising the mediating events
      affected by both mechanisms may lead to new approaches that mitigate secondary
      debilitating effects of cancer radiotherapy.

PMID- 24867692
TI  - Chemotherapy-induced dynamic gene expression changes in vivo are prognostic in
      ovarian cancer.
AB  - BACKGROUND: The response of ovarian cancer patients to carboplatin and paclitaxel
      is variable, necessitating identification of biomarkers that can reliably predict
      drug sensitivity and resistance. In this study, we sought to identify dynamically
      controlled genes and pathways associated with drug response and its time
      dependence. METHODS: Gene expression was assessed for 14 days post-treatment with
      carboplatin or carboplatin-paclitaxel in xenografts from two ovarian cancer
      models: platinum-sensitive serous adenocarcinoma-derived OV1002 and a mixed clear
      cell/endometrioid carcinoma-derived HOX424 with reduced sensitivity to platinum.
      RESULTS: Tumour volume reduction was observed in both xenografts, but more
      dominantly in OV1002. Upregulated genes in OV1002 were involved in DNA repair,
      cell cycle and apoptosis, whereas downregulated genes were involved in oxygen
      consuming metabolic processes and apoptosis control. Carboplatin-paclitaxel
      triggered a more comprehensive response than carboplatin only in both xenografts.
      In HOX424, apoptosis and cell cycle were upregulated, whereas Wnt signalling was
      inhibited. Genes downregulated after day 7 from both xenografts were predictive
      of overall survival. Overrepresented pathways were also predictive of outcome.
      CONCLUSIONS: Late expressed genes are prognostic in ovarian tumours in a dynamic
      manner. This longitudinal gene expression study further elucidates chemotherapy
      response in two models, stressing the importance of delayed biomarker detection
      and guiding optimal timing of biopsies.

PMID- 24867694
TI  - Response to comment on 'Interventions to improve exercise behaviour in sedentary
      people living with and beyond cancer: a systematic review'.

PMID- 24867693
TI  - Safety and efficacy of resistance training in germ cell cancer patients
      undergoing chemotherapy: a randomized controlled trial.
AB  - BACKGROUND: Bleomycin-etoposid-cisplatin (BEP) chemotherapy is curative in most
      patients with disseminated germ cell cancer (GCC) but also associated with toxic
      actions and dysfunction in non-targeted tissues. We investigated changes in
      muscle function during BEP and the safety and efficacy of resistance training to
      modulate these changes. METHODS: Thirty GCC patients were randomly assigned to
      resistance training (resistance training group (INT), n=15) or usual care (CON,
      n=15) during 9 weeks of BEP therapy. Resistance training consisted of thrice
      weekly sessions of four exercises, 3-4 sets/exercise of 10-15 repetitions at 12
      15 repetition maximum load. The primary endpoint was muscle fibre size, assessed
      in muscle biopsies from musculus vastus lateralis. Secondary endpoints were fibre
      phenotype composition, body composition, strength, blood biochemistry and patient
      reported endpoints. Healthy age-matched subjects (REF, n=19) performed the same
      RT-programme for comparison purposes. RESULTS: Muscle fibre size decreased by 
      322 MUm(2) (95% confidence interval (CI): -899 to 255; P=0.473) in the CON-group
      and increased by +206 MUm(2) (95% CI: -384 to 796; P=0.257) in the INT-group
      (adjusted mean difference (AMD), +625 MUm(2), 95% CI: -253 to 1503, P=0.149).
      Mean differences in type II fibre size (AMD, +823 MUm(2), P=0.09) and lean mass
      (AMD, +1.49 kg, P=0.07) in favour of the INT-group approached significance. The
      REF-group improved all muscular endpoints and had significantly superior changes
      compared with the INT-group (P<0.05). CONCLUSIONS: BEP was associated with
      significant reduction in lean mass and strength and trends toward unfavourable
      changes in muscle fibre size and phenotype composition. Resistance training was
      safe and attenuated dysfunction in selected endpoints, but BEP blunted several
      positive adaptations observed in healthy controls. Thus, our study does not
      support the general application of resistance training in this setting but larger
      scaled trials are required to confirm this finding.

PMID- 24867696
TI  - Childhood body mass index and the risk of prostate cancer in adult men.
AB  - BACKGROUND: Prostate cancer aetiology is poorly understood. It may have origins
      early in life; previously we found a positive association with childhood height.
      The effects of early life body mass index (BMI; kg m(-2)) on prostate cancer
      remain equivocal. We investigated if childhood BMI, independently and adjusted
      for height, is positively associated with adult prostate cancer. METHODS:
      Subjects were a cohort of 125208 boys formed from the Copenhagen School Health
      Records Register, born 1930-1969 with height and weight measurements at 7-13
      years. Cases were identified through linkage to the Danish Cancer Registry. Cox
      proportional hazards regressions were performed. RESULTS: Overall, 3355 men were
      diagnosed with prostate cancer. Body mass index during childhood was positively
      associated with adult prostate cancer. The hazard ratio of prostate cancer was
      1.06 (95% confidence interval (CI): 1.01-1.10) per BMI z-score at age 7, and 1.05
      (95% CI: 1.01-1.10) per BMI z-score at age 13. Estimates were similar and
      significant at all other ages. However, adjustment for childhood height
      attenuated the associations at all but the youngest ages as most estimates became
      nonsignificant. CONCLUSIONS: These results suggest that at most childhood ages,
      BMI does not confer an additional risk for prostate cancer beyond that of height.

PMID- 24867695
TI  - Profiling and targeting of cellular bioenergetics: inhibition of pancreatic
      cancer cell proliferation.
AB  - BACKGROUND: Targeting both mitochondrial bioenergetics and glycolysis pathway is
      an effective way to inhibit proliferation of tumour cells, including those that
      are resistant to conventional chemotherapeutics. METHODS: In this study, using
      the Seahorse 96-well Extracellular Flux Analyzer, we mapped the two intrinsic
      cellular bioenergetic parameters, oxygen consumption rate and proton production
      rate in six different pancreatic cancer cell lines and determined their
      differential sensitivity to mitochondrial and glycolytic inhibitors. RESULTS:
      There exists a very close relationship among intracellular bioenergetic
      parameters, depletion of ATP and anti-proliferative effects (inhibition of colony
      forming ability) in pancreatic cancer cells derived from different genetic
      backgrounds treated with the glycolytic inhibitor, 2-deoxyglucose (2-DG). The
      most glycolytic pancreatic cancer cell line was exquisitely sensitive to 2-DG,
      whereas the least glycolytic pancreatic cancer cell was resistant to 2-DG.
      However, when combined with metformin, inhibitor of mitochondrial respiration and
      activator of AMP-activated protein kinase, 2-DG synergistically enhanced ATP
      depletion and inhibited cell proliferation even in poorly glycolytic, 2-DG
      resistant pancreatic cancer cell line. Furthermore, treatment with conventional
      chemotherapeutic drugs (e.g., gemcitabine and doxorubicin) or COX-2 inhibitor,
      celecoxib, sensitised the cells to 2-DG treatment. CONCLUSIONS: Detailed
      profiling of cellular bioenergetics can provide new insight into the design of
      therapeutic strategies for inhibiting pancreatic cancer cell metabolism and
      proliferation.

PMID- 24867698
TI  - Genotoxic assessment in tobacco farmers at different crop times.
AB  - Agricultural workers engaged in tobacco cultivation are constantly exposed to
      large amounts of pesticides as well as to the nicotine present in raw tobacco
      leaves. Pesticides have been considered potential chemical mutagens: experimental
      data revealed that various agrochemicals possess mutagenic properties. Studies
      have affirmed that nicotine absorbed through the skin results in the
      characteristic green tobacco sickness (GTS), an occupational illness reported by
      tobacco workers. This study sought to determine genotoxic effects in farmers
      occupationally exposed to agrochemicals and nicotine. Peripheral blood samples
      were collected from 30 agricultural workers, at different crop times (off-season,
      during pesticides application and leaf harvest), and 30 were non-exposed. We
      obtained data on DNA damage detected by the Comet assay and Micronucleus test as
      biomarker of occupational exposure and effect. The serum cholinesterase level,
      which in general present relation with exposition to organophosphates and
      carbamates, as well as serum cotinine level, which is a metabolite of nicotine,
      were also evaluated. The results showed a significant increase in Damage index
      and frequency in tobacco farmers compared to the non-exposed group, for all
      different crop times; and a significant increase in micronucleated cells in the
      off-season group. No correlation was found between age and exposure time in
      relation to biomarker tests. The DNA damage was greater in males than in females,
      but with a significant difference only in off-season group. No difference, in
      cholinesterase activity, was seen among the group of farmers and non-exposed
      group. Elevated level of cotinine was observed in leaf harvest group. This
      investigation suggests increased DNA damage in all tobacco crop stages, calling
      attention to the significant increase during the off-season and tobacco leaf
      harvest. 

PMID- 24867697
TI  - Sentinel lymph node biopsy in vulval cancer: systematic review and meta-analysis.
AB  - BACKGROUND: The purpose of this study was to determine the accuracy of sentinel
      lymph node (SLN) biopsy with technetium 99 (99mTc) and/or blue dye-enhanced
      lymphoscintigraphy in vulval cancer. METHODS: Sensitive searches of databases
      were performed upto October 2013. Studies with at least 75% of women with FIGO
      stage IB or II vulval cancer evaluating SLN biopsy with 99mTc, blue dye or both
      with reference standard of inguinofemoral lymphadenectomy (IFL) or clinical
      follow-up were included. Meta-analyses were performed using Meta-Disc version
      1.4. RESULTS: Of the 2950 references, 29 studies (1779 women) were included; most
      of them evaluated 99mTc combined with blue dye. Of these, 24 studies reported
      results for SLN followed by IFL, and 5 reported clinical follow-up only for SLN
      negatives. Pooling of all studies was inappropriate because of heterogeneity.
      Mean SLN detection rates were 94.0% for 99mTc, 68.7% for blue dye and 97.7% for
      both. SLN biopsy had pooled sensitivity of 95% (95% CI 92-98%) with negative
      predictive value (NPV) of 97.9% in studies using 99mTc/blue dye, ultrastaging and
      immunohistochemistry with IFL as reference. Pooled sensitivity for SLN with
      clinical follow-up for SLN-negatives was 91% (85-95%) with NPV 95.6%. Patients
      undergoing SLN biopsy experienced less morbidity than those undergoing IFL.
      CONCLUSIONS: Sentinel lymph node biopsy using 99mTC, blue dye and ultrastaging
      with immunohistochemistry is highly accurate when restricted to carefully
      selected patients, within a rigorous protocol, with close follow-up and where
      sufficient numbers for learning curve optimisation exist. Patients must make an
      informed choice between the slightly higher groin recurrence rates of SLN biopsy
      vs the greater morbidity of IFL.

PMID- 24867699
TI  - An uncertainty and sensitivity analysis applied to the prioritisation of
      pharmaceuticals as surface water contaminants from wastewater treatment plant
      direct emissions.
AB  - In this study, the concentration probability distributions of 82 pharmaceutical
      compounds detected in the effluents of 179 European wastewater treatment plants
      were computed and inserted into a multimedia fate model. The comparative
      ecotoxicological impact of the direct emission of these compounds from wastewater
      treatment plants on freshwater ecosystems, based on a potentially affected
      fraction (PAF) of species approach, was assessed to rank compounds based on
      priority. As many pharmaceuticals are acids or bases, the multimedia fate model
      accounts for regressions to estimate pH-dependent fate parameters. An uncertainty
      analysis was performed by means of Monte Carlo analysis, which included the
      uncertainty of fate and ecotoxicity model input variables, as well as the spatial
      variability of landscape characteristics on the European continental scale.
      Several pharmaceutical compounds were identified as being of greatest concern,
      including 7 analgesics/anti-inflammatories, 3 beta-blockers, 3 psychiatric drugs,
      and 1 each of 6 other therapeutic classes. The fate and impact modelling relied
      extensively on estimated data, given that most of these compounds have little or
      no experimental fate or ecotoxicity data available, as well as a limited reported
      occurrence in effluents. The contribution of estimated model input variables to
      the variance of freshwater ecotoxicity impact, as well as the lack of
      experimental abiotic degradation data for most compounds, helped in establishing
      priorities for further testing. Generally, the effluent concentration and the
      ecotoxicity effect factor were the model input variables with the most
      significant effect on the uncertainty of output results. 

PMID- 24867700
TI  - Concentration profiles and spatial distribution of perfluoroalkyl substances in
      an industrial center with condensed fluorochemical facilities.
AB  - Jiangsu Hi-tech Fluorochemical Industry Park, China, is one of the largest
      fluorochemical industry centers in Asia and could be a point source of
      polyfluoroalkyl substances (PFASs) to the surrounding environment. Besides water,
      sediment and soil samples, tree leaves and bark were also collected to monitor
      airborne PFASs around the facilities. Perfluorooctanoic acid and short-chain
      perfluorocarboxylates including perfluorohexanoic acid and perfluoropentanoic
      acid were found predominantly in all the samples. The target ?PFASs were
      distributed in the dissolved phase with a proportion of 96.5+/-2.9%. High
      concentrations of ?PFASs (up to 12,700 ng/L in surface water) were found at sites
      near and within the wastewater treatment plant and the facilities. The ?PFASs in
      the sediment/sludge were in the range of 3.33-324 ng/g dw. For the first time,
      tree samples were used for bio-monitoring airborne PFASs in the environment. The
      ?PFASs in the tree leaf and bark samples were in the range of 10.0-276 and 6.76
      120 ng/g dw, respectively. The spatial distribution of ?PFASs in the tree leaves
      suggested that airborne PFASs could be transported from the center to the
      surrounding environment by prevailing wind.

PMID- 24867701
TI  - Impact of activated sludge configuration and operating conditions on in vitro and
      in vivo responses and trace organic compound removal.
AB  - This study tested municipal sewage effluents generated at the pilot scale using
      conventional activated sludge (CAS), nitrifying activated sludge (CAS-N) and
      biological nutrient removal (BNR) in terms of the removal of trace organic
      compounds (TrOCs) and final effluent quality as indicated by yeast estrogenicity
      screening (YES), short term zebrafish reproduction and fathead minnow life-cycle
      tests. Under cold weather conditions (extended SRTs), the BNR configuration
      reduced the concentrations of the largest number of TrOCs while under warm
      weather conditions (reduced SRTs) the CAS-N was most effective. By comparison,
      YES test results indicated statistically lower responses in the BNR effluent in
      the warm weather tests and no difference between the effluents of CAS-N and BNR
      in the cold weather tests. Short term tests with adult zebrafish revealed no
      impact of the BNR and CAS-N effluents on egg production. By contrast egg
      production and gene expression in the CAS-exposed zebrafish were substantially
      less than that of control exposures and were similar to that of exposures to
      ammonia at similar concentrations as the CAS exposures. In fathead minnow life
      cycle tests, exposures to CAS effluent (70-50% v/v) resulted in considerable
      mortality, reduced growth and reduced egg production that was likely due to the
      elevated ammonia concentrations. The CAS-N effluent (100% v/v) also resulted in
      some mortality and reduced growth and egg production in the fathead minnows. By
      contrast, the BNR effluent (100% v/v) had no effect on mortality, growth or egg
      production. The results suggest that enhancements to wastewater treatment plants
      that are associated with improved nitrogen removal can result in enhanced removal
      of TrOCs and can reduce the harmful effects of the effluents on aquatic biota. 

PMID- 24867702
TI  - Long-term (1930-2010) trends in groundwater levels in Texas: influences of soils,
      landcover and water use.
AB  - Rapid groundwater depletion has raised grave concerns about sustainable
      development in many parts of Texas, as well as in other parts of the world.
      Previous hydrologic investigations on groundwater levels in Texas were conducted
      mostly on aquifer-specific basis, and hence lacked state-wide panoramic view. The
      aim of this study was to present a qualitative overview of long-term (1930-2010)
      trends in groundwater levels in Texas and identify spatial patterns by applying
      different statistical (boxplots, correlation-regression, hierarchical cluster
      analysis) and geospatial techniques (Moran's I, Local Indicators of Spatial
      Association) on 136,930 groundwater level observations from Texas Water
      Development Board's database. State-wide decadal median water-levels declined
      from about 14 m from land surface in the 1930s to about 36 m in the 2000s. Number
      of counties with deeper median water-levels (water-level depth>100 m) increased
      from 2 to 13 between 1930s and 2000s, accompanied by a decrease in number of
      counties having shallower median water-levels (water-level depth<25 m) from 134
      to 113. Water-level declines across Texas, however, mostly followed logarithmic
      trends marked by leveling-off phenomena in recent times. Assessment of water
      levels by Groundwater Management Areas (GMA), management units created to address
      groundwater depletion issues, indicated hotspots of deep water-levels in Texas
      Panhandle and GMA 8 since the 1960s. Contrasting patterns in water use,
      landcover, geology and soil properties distinguished Texas Panhandle from GMA 8.
      Irrigated agriculture is the major cause of depletion in the Texas Panhandle as
      compared to increasing urbanization in GMA 8. Overall our study indicated that
      use of robust spatial and statistical methods can reveal important details about
      the trends in water-level changes and shed lights on the associated factors. Due
      to very generic nature, techniques used in this study can also be applied to
      other areas with similar eco-hydrologic issues to identify regions that warrant
      future management actions.

PMID- 24867703
TI  - The pollution levels of BTEX and carbonyls under haze and non-haze days in
      Beijing, China.
AB  - The North China Plain including Beijing is frequently suffering from serious haze
      days in recent years. To best recognize the influence of haze days on regional
      air quality, the pollution levels of deleterious gases of BTEX (benzene, toluene,
      ethylbenzene, m,p-xylene and o-xylene) and carbonyls (formaldehyde, acetaldehyde
      and acetone) under haze and non-haze days were contrastively investigated during
      the period of September 2008-August 2010 in Beijing. In comparison with non-haze
      days, remarkable enhancement of BTEX and the carbonyls under haze days in winter
      was found, with enhancement factors of 1.9-5.7 for BTEX and of 1.5-4.2 for the
      carbonyls. Whereas the enhancement factors for both BTEX (1.0-3.0) and the
      carbonyls (1.2-1.9) under haze days in summer were relatively small. The ratios
      of each BTEX to CO under both haze days and non-haze days exhibited a minimal
      value in the afternoon, whereas maximal values for the ratios of the carbonyls to
      CO were usually found in the afternoon. The ratios of each BTEX to CO were
      extremely greater under haze days than those under non-haze days in winter, but
      no evident difference was found in summer. The ratios of each carbonyl under both
      haze days and non-haze days in summer were at least a factor of 2 greater than
      those in winter and only enhancement of the ratios under haze days was found in
      winter. The remarkably higher ratios of ethylbenzene to m,p-xylene under haze
      days than non-haze days in both winter and summer revealed high reactivity of
      photochemical reactions initiated by OH radicals under haze days. 

PMID- 24867704
TI  - Soil microbial properties after long-term swine slurry application to
      conventional and no-tillage systems in Brazil.
AB  - Swine waste can be used as an agricultural fertilizer, but large amounts may
      accumulate excess nutrients in soil or contaminate the surrounding environment.
      This study evaluated long-term soil amendment (15 years) with different levels of
      swine slurry to conventional (plow) tillage (CT) and no tillage (NT) soils. Long
      term swine slurry application did not affect soil organic carbon. Some chemical
      properties, such as calcium, base saturation, and aluminum saturation were
      significantly different within and between tillages for various application
      rates. Available P and microbial parameters were significantly affected by slurry
      addition. Depending on tillage, soil microbial biomass and enzyme activity
      increased up to 120 m(3) ha(-1) year(-1) in all application rates. The NT system
      had higher microbial biomass and activity than CT at all application levels.
      There was an inverse relationship between the metabolic quotient (qCO2) and MBC,
      and the qCO2 was 53% lower in NT than CT. Swine slurry increased overall acid
      phosphatase activity, but the phosphatase produced per unit of microbial biomass
      decreased. A comparison of data obtained in the 3rd and 15th years of swine
      slurry application indicated that despite slurry application the CT system
      degraded with time while the NT system had improved values of soil quality
      indicators. For these Brazilian oxisols, swine slurry amendment was insufficient
      to maintain soil quality parameters in annual crop production without additional
      changes in tillage management.

PMID- 24867705
TI  - Application of TaqMan fluorescent probe-based quantitative real-time PCR assay
      for the environmental survey of Legionella spp. and Legionella pneumophila in
      drinking water reservoirs in Taiwan.
AB  - In this study, TaqMan fluorescent quantitative real-time PCR was performed to
      quantify Legionella species in reservoirs. Water samples were collected from 19
      main reservoirs in Taiwan, and 12 (63.2%) were found to contain Legionella spp.
      The identified species included uncultured Legionella spp., L. pneumophila, L.
      jordanis, and L. drancourtii. The concentrations of Legionella spp. and L.
      pneumophila in the water samples were in the range of 1.8*10(2)-2.6*10(3) and
      1.6*10(2)-2.4*10(2) cells/L, respectively. The presence and absence of Legionella
      spp. in the reservoir differed significantly in pH values. These results
      highlight the importance that L. pneumophila, L. jordanis, and L. drancourtii are
      potential pathogens in the reservoirs. The presence of L. pneumophila in
      reservoirs may be a potential public health concern that must be further
      examined.

PMID- 24867706
TI  - Pilot study of seasonal occurrence and distribution of antibiotics and drug
      resistant bacteria in wastewater treatment plants in Slovakia.
AB  - This work presents environmental and quality-control data from the analyses of 33
      antibiotics in influent and effluent water from two waste water treatment plants
      (WWTPs) in the capital and the biggest city of Slovakia. Seeing that consumption
      of antibiotics depends on epidemiological season, samples were collected during
      February and August. Among assessed antibiotics ciprofloxacin and clarithromycin
      were detected in highest concentrations in influent water. Seasonal changes were
      observed only in plant A when antibiotic concentrations decreased. On the other
      hand an increase in some cases was observed in plant B. Insufficient degradation
      of some macrolides, sulfonamides and trimethoprim was detected according to their
      higher concentrations in effluent water. Contact of antibiotics in subinhibitory
      concentrations and sludge bacteria in WWTPs represent the base for the
      development of significant levels of microbial resistance. Simultaneously,
      antibiotic resistance of fecal coliforms and fecal streptococci from sewage
      sludge was evaluated. Majority of coliform bacteria were found to be resistant to
      ampicillin and gentamicin. A significant seasonal difference was determined only
      in case of high-level resistance. In summer samples, an increase in the strains
      resistant to concentrations higher than the resistance breakpoints established by
      EUCAST and NCCLS was observed. No antibiotic resistance in streptococci was
      observed. However, as a part of sewage sludge is mixed with compost and utilized
      in agriculture, better processing of sludge should be considered. 

PMID- 24867707
TI  - Integrated biomarker analysis of chlorpyrifos metabolism and toxicity in the
      earthworm Aporrectodea caliginosa.
AB  - To increase our understanding about the mode of toxic action of organophosphorus
      pesticides in earthworms, a microcosm experiment was performed with Aporrectodea
      caliginosa exposed to chlorpyrifos-spiked soils (0.51 and 10 mg kg(-1) dry soil)
      for 3 and 21 d. Acetylcholinesterase (AChE), carboxylesterase (CbE), cytochrome
      P450-dependent monooxygenase (CYP450), and glutathione S-transferase (GST)
      activities were measured in the body wall of earthworms. With short-term
      exposure, chlorpyrifos inhibited CbE activity (51-89%) compared with controls in
      both treated groups, whereas AChE activity was depressed in the 10-mg kg(-1)
      group (87% inhibition). With long-term exposure, chlorpyrifos strongly inhibited
      all esterase activities (84-97%). Native electrophoresis revealed three AChE
      isozymes, two of which showed a decreased staining corresponding to the level of
      pesticide exposure. The impact of chlorpyrifos on CbE activity was also
      corroborated by zymography. CYP450 activity was low in unexposed earthworms, but
      it increased (1.5- to 2.4-fold compared to controls) in the earthworms exposed to
      both chlorpyrifos concentrations for 3d. Bioactivation of chlorpyrifos was
      determined by incubating the muscle homogenate in the presence of chlorpyrifos
      and NAD(H)2. The mean (+/-SD, n=40) bioactivation rate in the unexposed
      earthworms was 0.74+/-0.27 nmol NAD(H)2 oxidized min(-1) mg(-1) protein, and a
      significant induction was detected in the low/short-term exposure group. GST
      activity significantly increased (33-35% of controls) in earthworms short-term
      exposed to both chlorpyrifos concentrations. Current data showed that CYP450 and
      GST activities had a prominent role in the initial exposure to the
      organophosphorus. With short-term exposure, CbE activity was also a key enzyme in
      the non-catalytic detoxification of chlorpyrifos-oxon, thereby reducing its
      impact on AChE activity, before it became saturated at t=21 d. Results indicate
      that A. caliginosa detoxify efficiently chlorpyrifos, which would explain its
      tolerance to relatively high exposure levels to chlorpyrifos.

PMID- 24867708
TI  - Sources and fates of heavy metals in a mining-impacted stream: temporal
      variability and the role of iron oxides.
AB  - Heavy metal contamination of surface waters at mining sites often involves
      complex interactions of multiple sources and varying biogeochemical conditions.
      We compared surface and subsurface metal loading from mine waste pile runoff and
      mine drainage discharge and characterized the influence of iron oxides on metal
      fate along a 0.9-km stretch of Tar Creek (Oklahoma, USA), which drains an
      abandoned Zn/Pb mining area. The importance of each source varied by metal; mine
      waste pile runoff contributed 70% of Cd, while mine drainage contributed 90% of
      Pb, and both sources contributed similarly to Zn loading. Subsurface inputs
      accounted for 40% of flow and 40-70% of metal loading along this stretch.
      Streambed iron oxide aggregate material contained highly elevated Zn (up to
      27,000 MUg g(-1)), Pb (up to 550 MUg g(-1)) and Cd (up to 200 MUg g(-1)) and was
      characterized as a heterogeneous mixture of iron oxides, fine-grain mine waste,
      and organic material. Sequential extractions confirmed preferential sequestration
      of Pb by iron oxides, as well as substantial concentrations of Zn and Cd in iron
      oxide fractions, with additional accumulation of Zn, Pb, and Cd during downstream
      transport. Comparisons with historical data show that while metal concentrations
      in mine drainage have decreased by more than an order of magnitude in recent
      decades, the chemical composition of mine waste pile runoff has remained
      relatively constant, indicating less attenuation and increased relative
      importance of pile runoff. These results highlight the importance of monitoring
      temporal changes at contaminated sites associated with evolving speciation and
      simultaneously addressing surface and subsurface contamination from both mine
      waste piles and mine drainage.

PMID- 24867709
TI  - Green roofs for a drier world: effects of hydrogel amendment on substrate and
      plant water status.
AB  - Climate features of the Mediterranean area make plant survival over green roofs
      challenging, thus calling for research work to improve water holding capacities
      of green roof systems. We assessed the effects of polymer hydrogel amendment on
      the water holding capacity of a green roof substrate, as well as on water status
      and growth of Salvia officinalis. Plants were grown in green roof experimental
      modules containing 8 cm or 12 cm deep substrate (control) or substrate mixed with
      hydrogel at two different concentrations: 0.3 or 0.6%. Hydrogel significantly
      increased the substrate's water content at saturation, as well as water available
      to vegetation. Plants grown in 8 cm deep substrate mixed with 0.6% of hydrogel
      showed the best performance in terms of water status and membrane integrity under
      drought stress, associated to the lowest above-ground biomass. Our results
      provide experimental evidence that polymer hydrogel amendments enhance water
      supply to vegetation at the establishment phase of a green roof. In particular,
      the water status of plants is most effectively improved when reduced substrate
      depths are used to limit the biomass accumulation during early growth stages. A
      significant loss of water holding capacity of substrate-hydrogel blends was
      observed after 5 months from establishment of the experimental modules. We
      suggest that cross-optimization of physical-chemical characteristics of hydrogels
      and green roof substrates is needed to improve long term effectiveness of polymer
      hydrogel blends.

PMID- 24867710
TI  - In vivo imaging of specific drug-target binding at subcellular resolution.
AB  - The possibility of measuring binding of small-molecule drugs to desired targets
      in live cells could provide a better understanding of drug action. However,
      current approaches mostly yield static data, require lysis or rely on indirect
      assays and thus often provide an incomplete understanding of drug action. Here,
      we present a multiphoton fluorescence anisotropy microscopy live cell imaging
      technique to measure and map drug-target interaction in real time at subcellular
      resolution. This approach is generally applicable using any fluorescently
      labelled drug and enables high-resolution spatial and temporal mapping of bound
      and unbound drug distribution. To illustrate our approach we measure
      intracellular target engagement of the chemotherapeutic Olaparib, a poly(ADP
      ribose) polymerase inhibitor, in live cells and within a tumour in vivo. These
      results are the first generalizable approach to directly measure drug-target
      binding in vivo and present a promising tool to enhance understanding of drug
      activity. 

PMID- 24867711
TI  - Nutritional aspects of beta-carotene and resveratrol antioxidant synergism in
      giant unilamellar vesicles.
AB  - Giant unilamellar vesicles of soy phosphatidylcholine are found to undergo
      budding when sensitized with chlorophyll a ([phosphatidylcholine] : [chlorophyll
      a] = 1500 : 1) under light irradiation (400-440 nm, 16 mW mm(-2)). 'Entropy' as a
      dimensionless image heterogeneity measurement is found to increase linearly with
      time during an initial budding process. For beta-carotene addition
      ([phosphatidylcholine] : [beta-carotene] = 500 : 1), a lag phase of 23 s is
      observed, followed by a budding process at an initial rate lowered by a factor of
      3.8, whereas resveratrol ([phosphatidylcholine] : [resveratrol] = 500 : 1) has
      little if any protective effect against budding. However, resveratrol, when
      combined with beta-carotene, is found to further reduce the initial budding rate
      by a total factor of 4.7, exhibiting synergistic antioxidation effects. It is
      also interesting that beta-carotene alone determines the lag phase for the
      initiation of budding, while resveratrol supports beta-carotene in reducing the
      rate of the budding process following the lag phase; however, it alone has no
      observable effect on the lag phase. Resveratrol is suggested to regenerate beta
      carotene following its sacrificial protection of unsaturated lipids from
      oxidative stress, modeling the synergistic effects in cell membranes by
      combinations of dietary antioxidants. 

PMID- 24867712
TI  - Reward anticipation enhances brain activation during response inhibition.
AB  - The chance to achieve a reward starts up the required neurobehavioral mechanisms
      to adapt our thoughts and actions in order to accomplish our objective. However,
      reward does not equally reinforce everybody but depends on interindividual
      motivational dispositions. Thus, immediate reward contingencies can modulate the
      cognitive process required for goal achievement, while individual differences in
      personality can affect this modulation. We aimed to test the interaction between
      inhibition-related brain response and motivational processing in a stop signal
      task by reward anticipation and whether individual differences in sensitivity to
      reward (SR) modulate such interaction. We analyzed the cognitive-motivational
      interaction between the brain pattern activation of the regions involved in
      correct and incorrect response inhibition and the association between such brain
      activations and SR scores. We also analyzed the behavioral effects of reward on
      both reaction times for the "go" trials before and after correct and incorrect
      inhibition in order to test error prediction performance and postinhibition
      adjustment. Our results show enhanced activation during response inhibition under
      reward contingencies in frontal, parietal, and subcortical areas. Moreover,
      activation of the right insula and the left putamen positively correlates with
      the SR scores. Finally, the possibility of reward outcome affects not only
      response inhibition performance (e.g., reducing stop signal reaction time), but
      also error prediction performance and postinhibition adjustment. Therefore,
      reward contingencies improve behavioral performance and enhance brain activation
      during response inhibition, and SR is related to brain activation. Our results
      suggest the conditions and factors that subserve cognitive control strategies in
      cognitive motivational interactions during response inhibition. 

PMID- 24867714
TI  - The impact of conflicts of interest in plastic surgery: an analysis of acellular
      dermal matrix, implant-based breast reconstruction.
AB  - BACKGROUND: Although conflicts of interest in biomedical research have received
      significant attention, the impact of conflicts of interest on surgical outcomes
      has not been fully explored. METHODS: A systematic electronic search of the
      literature was performed for studies that evaluated surgical outcomes in
      acellular dermal matrix and non-acellular dermal matrix implant-based breast
      reconstruction. Surgical complications, including infection, seroma, hematoma,
      necrosis, and explantation, were used as outcome metrics and extracted from
      studies. Surgical outcomes were then pooled and compared between studies that
      disclosed conflicts of interest and those that did not disclose conflicts of
      interest. RESULTS: A total of 776 abstracts were identified, of which only 35
      fulfilled the authors' inclusion criteria. Conflicts of interest were reported in
      14 of these abstracts (40 percent). The pooled data from studies that reported no
      conflicts of interest and studies that reported conflicts of interest included a
      total of 8241 and 5384 breasts and 2852 and 1864 patients, respectively.
      Considered collectively, surgical complications were less common in studies that
      reported a conflict of interest than in studies that reported no conflicts of
      interest. When surgical outcome data were further stratified by acellular dermal
      matrix use, surgical complications were less common in studies with conflicts of
      interest when acellular dermal matrix was used. However, when acellular dermal
      matrix was not used, surgical complications were similar between authors that
      reported a conflict of interest and those that did not report a conflict of
      interest. CONCLUSIONS: Self-reported conflicts of interest are common in implant
      based breast reconstruction research. Studies authored by groups with conflicts
      of interest are significantly associated with reporting lower surgical
      complications and therefore describing positive research findings, especially
      when industry-marketed products are being used in the study. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

PMID- 24867715
TI  - High-frequency radiowave electrosurgery for persistent conjunctival chemosis
      following cosmetic blepharoplasty.
AB  - BACKGROUND: Conjunctival chemosis often complicates cosmetic lower eyelid
      blepharoplasty. With the conventional approaches, including medical or surgical
      methods, irritative symptoms are produced and complete recovery is delayed. The
      authors introduced a new simple surgical approach for treating persistent
      conjunctival chemosis following cosmetic blepharoplasty. METHODS: Eleven patients
      (12 eyes) with persistent chemosis lasting 6 weeks to 2 years were recruited for
      this study. Subconjunctival coagulation on the edematous conjunctiva was
      performed with a fine-needle electrode using a high-frequency radiowave
      electrosurgical unit in coagulation mode, and subconjunctival fluid drainage was
      performed by gentle pressure with a wet applicator. After the procedures, topical
      steroid and antibiotic eye drops were given four times per day for 1 month.
      RESULTS: Chemosis in 11 eyes (91.7 percent) was resolved within 1 week and
      remained stable for a follow-up period of 6 months. Recurrence of chemosis and
      complications related to the procedure were not noted during the follow-up.
      CONCLUSIONS: A surgical approach with high-frequency radiowave electrosurgery
      produced a significant reduction of persistent chemosis and provided prompt
      symptom improvement. This procedure can be considered as a simple and safe method
      of treating persistent conjunctival chemosis following cosmetic blepharoplasty.
      CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 24867713
TI  - Association of T-cell immunoglobulin and mucin domain-containing molecule 3 (Tim
      3) polymorphisms with susceptibility and disease progression of HBV infection.
AB  - PURPOSE: T-cell immunoglobulin and mucin domain-containing molecule 3 (Tim-3)
      plays an important role in regulating T cells in hepatitis B virus (HBV)
      infection and hepatocellular carcinoma (HCC). However, few researches have
      reported the association of Tim-3 genetic variants with susceptibility and
      progression of HBV infection. In this study, we focused on the association of Tim
      3 polymorphisms with HBV infection, HBsAg seroclearance and hepatocellular
      carcinoma. METHODS: A total of 800 subjects were involved in this study. Four
      groups were studied here, including HBV, HBsAg seroclearance, HBV-associated HCC
      and healthy controls. Three single-nucleotide polymorphisms (SNPs) of Tim-3,
      rs246871, rs25855 and rs31223 were genotyped to analyze the association of Tim-3
      polymorphisms with susceptibility and disease progression of HBV infection.
      RESULTS: Our study found that rs31223 and rs246871 were associated with disease
      progression of HBV infection, while none of the three SNPs was relevant to HBV
      susceptibility. The minor allele "C" of rs31223 was found to be associated with
      an increased probability of HBsAg seroclearance (P = 0.033) and genotype "CC" of
      rs246871 to be associated with an increased probability of HBV-associated HCC (P
      = 0.007). In accordance, haplotypic analysis of the three polymorphisms also
      showed that the haplotype block CGC* and TGC* were significantly associated with
      HBsAg seroclearance (P<0.05) while haplotype block CAT*, CGT*, TAC* and TGT* were
      significantly associated with HBV-associated HCC (all P<0.05). CONCLUSIONS:
      Genetic variants of Tim-3 have an important impact on disease progression of HBV
      infection. With specific Tim-3 polymorphisms, patients infected with HBV could be
      potential candidates of HCC and HBsAg seroclearance.

PMID- 24867716
TI  - Engineered nasal cartilage by cell homing: a model for augmentative and
      reconstructive rhinoplasty.
AB  - BACKGROUND: Current augmentative and reconstructive rhinoplasties use auto logous
      tissue grafts or synthetic bioinert materials to repair nasal trauma or attain an
      aesthetic shape. Autologous grafts are associated with donor-site trauma and
      morbidity. Synthetic materials are widely used but often yield an unnatural
      appearance and are prone to infection or dislocation. There is an acute clinical
      need for the generation of native tissues to serve as rhinoplasty grafts without
      the undesirable features that are associated with autologous grafts or current
      synthetic materials. METHODS: Bioactive scaffolds were developed that not only
      recruited cells in the nasal dorsum in vivo, but also induced chondrogenesis of
      the recruited cells. Bilayered scaffolds were fabricated with alginate-containing
      gelatin microspheres encapsulating cytokines atop a porous poly(lactic-co
      glycolic acid) base. Microspheres were fabricated to contain recombinant human
      transforming growth factor-beta3 at doses of 200, 500, or 1000 ng, with phosphate
      buffered saline-loaded microspheres used as a control. A rat model of
      augmentation rhinoplasty was created by implanting scaffolds atop the native
      nasal cartilage surface that was scored to induce cell migration. Tissue
      formation and chondrogenesis in the scaffolds were evaluated by image analysis
      and histologic staining with hematoxylin and eosin, toluidine blue, Verhoeff
      elastic-van Geison, and aggrecan immunohistochemistry. RESULTS: Sustained release
      of increasing doses of transforming growth factor-beta3 for up to the tested 10
      weeks promoted orthotopic cartilage-like tissue formation in a dose-dependent
      manner. CONCLUSIONS: These findings represent the first attempt to engineer
      cartilage tissue by cell homing for rhinoplasty, and could potentially serve as
      an alternative material for augmentative and reconstructive rhinoplasty.

PMID- 24867718
TI  - Discussion: Natrelle round silicone breast implants: core study results at 10
      years.

PMID- 24867717
TI  - Natrelle round silicone breast implants: Core Study results at 10 years.
AB  - BACKGROUND: Allergan's Natrelle round silicone-filled breast implants were
      approved by the U.S. Food and Drug Administration in 2006 based on interim
      results from the Core Study; final 10-year study results are now available.
      METHODS: Seven hundred fifteen subjects were implanted with smooth and Biocell
      textured Natrelle round silicone implants and attended clinic visits at 0 to 4
      weeks, 6 months, 1 year, and annually through 10 years. Approximately one-third
      of subjects underwent magnetic resonance imaging at years 1, 3, 5, 7, and 9 to
      assess rupture. RESULTS: Complication rates showed modest increases over the
      previously published 6-year rates. The Kaplan-Meier capsular contracture rate was
      18.9 percent for augmentation, 28.7 percent for revision-augmentation, and 24.6
      percent for reconstruction. Among augmentation subjects, capsular contracture was
      significantly lower (p = 0.023) for submuscular (15.7 percent) versus
      subglandular (26.3 percent) placement. The overall rupture rate in the magnetic
      resonance imaging cohort was 13.0 percent for subjects and 7.7 percent for
      implants. By the end of the study, 81.8 percent of augmentation subjects still
      had an original implant in place. Using a five-point scale, 94.2 percent of
      augmentation, 83.8 percent of revision-augmentation, and 90.7 percent of
      reconstruction subjects reported being satisfied or definitely satisfied with
      their implants. Significant improvement over baseline was also seen in overall
      breast satisfaction and satisfaction with breast size, shape, feel, and how well
      they matched. CONCLUSION: The 10-year data from the Natrelle Core Study, which
      can guide surgeons and patients in decision-making, demonstrate safety and high
      levels of patient satisfaction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic,
      III.

PMID- 24867719
TI  - Low harvest pressure enhances autologous fat graft viability.
AB  - Autologous fat grafting has been widely used in reconstructive and cosmetic
      surgery. Harvesting techniques play a key role in graft viability and outcomes.
      The authors investigated the effect of harvest pressure on adipocyte survival and
      viability of the surviving cells. Abdominal lipoaspiration was performed at high
      pressure (-760 mmHg) and low pressure (-250 mmHg) on three patients. Adipocyte
      survival and cell viability were measured. Adipocyte count immediately after
      harvest was 47 percent higher when aspirated at low pressure compared with high
      pressure. In addition, the cell viability was significantly higher at day 7 with
      low-pressure aspiration. The authors also describe a simple technique for
      aspirating at low pressures to obtain a controlled, consistent, reproducible, and
      good quality graft.

PMID- 24867720
TI  - Megavolume autologous fat transfer: part II. Practice and techniques.
AB  - The authors describe the techniques that use the principles of fat grafting to
      allow them to successfully graft megavolumes (250-ml range) of autologous fat
      into breasts. The Brava external volume expansion device preoperatively increases
      the volume and vascularity of the recipient site. Low-pressure liposuction and
      minimal centrifugation are used to gently extract and purify the adipose tissue
      with minimal trauma. Even and diffuse reinjection of the fat increases graft-to
      recipient interface and reduces interstitial fluid pressure. Postoperative Brava
      use protects the graft and acts as a three-dimensional immobilizing splint. By
      adhering to these techniques, we have been able to graft megavolumes of fat into
      the breasts of over 1000 patients and obtain substantial long-term volume
      retention.

PMID- 24867721
TI  - Regenerative peripheral nerve interface viability and signal transduction with an
      implanted electrode.
AB  - BACKGROUND: The regenerative peripheral nerve interface is an internal interface
      for signal transduction with external electronics of prosthetic limbs; it
      consists of an electrode and a unit of free muscle that is neurotized by a
      transected residual peripheral nerve. Adding a conductive polymer coating on
      electrodes improves electrode conductivity. This study examines regenerative
      peripheral nerve interface tissue viability and signal fidelity in the presence
      of an implanted electrode coated or uncoated with a conductive polymer. METHODS:
      In a rat model, the extensor digitorum longus muscle was moved as a
      nonvascularized free tissue transfer and neurotized by the divided peroneal
      nerve. Either a stainless steel pad electrode (n = 8) or a pad electrode coated
      with poly(3,4-ethylenedioxythiophene) conductive polymer (PEDOT) (n = 8) was
      implanted on the muscle transfer and secured with an encircling acellular
      extracellular matrix. The contralateral muscle served as the control. RESULTS:
      The free muscle transfers were successfully revascularized and over time
      reinnervated as evidenced by serial insertional needle electromyography. Compound
      muscle action potentials were successfully transduced through the regenerative
      peripheral nerve interface. The conductive polymer coating on the implanted
      electrode resulted in increased recorded signal amplitude that was observed
      throughout the course of the study. Histologic examination confirmed axonal
      sprouting, elongation, and synaptogenesis within regenerative peripheral nerve
      interface regardless of electrode type. CONCLUSIONS: The regenerative peripheral
      nerve interface remains viable over seven months in the presence of an implanted
      electrode. Electrodes with and without conductive polymer reliably transduced
      signals from the regenerative peripheral nerve interface. Electrodes with a
      conductive polymer coating resulted in recording more of the regenerative
      peripheral nerve interface signal.

PMID- 24867722
TI  - Autologous fat grafting alleviates burn-induced neuropathic pain in rats.
AB  - BACKGROUND: The management of neuropathic pain after burn injury is a critical
      clinical issue. Autologous fat grafting has been shown to alleviate neuropathic
      pain in certain cases, but has not been shown to alleviate the pain associated
      with burn-induced scars. The authors assessed the effectiveness of autologous fat
      grafting for the management of pain in burn-induced scars. METHODS: One paw of
      the experimental rats received a third-degree burn using a heated metal block.
      Neuropathic pain in the affected paw was assessed based on behavioral responses
      to thermal and mechanical stimuli. A graft (0.4 ml of autologous fat or a sham
      graft) was administered by injection to the burn scar and sham-burned paw. The
      animals were killed 4 weeks after the fat graft treatments; Masson trichrome
      stain of hind-paw skin and expression of phosphorylated p38 and OX42 in the
      dorsal horns of the spinal cords were examined. RESULT: The third-degree burns
      were completely healed at 4 weeks. Burn-induced scarring caused mechanical
      allodynia and increased the expression of phosphorylated p38 and OX42 in spinal
      cord dorsal horn microglial cells. Autologous fat grafting significantly
      alleviated mechanical allodynia (p < 0.05), and immunohistochemistry showed that
      the expression of phosphorylated p38 and OX42 was significantly lower in spinal
      cord dorsal horn microglial cells 4 weeks after fat grafting (p < 0.05).
      CONCLUSIONS: Autologous fat grafting is used daily in clinical practice. It is an
      effective treatment for the relief of burn-induced mechanical allodynia in rats.
      Further investigation of the clinical use of autologous fat grafting in burn
      patients is warranted.

PMID- 24867723
TI  - A novel and effective strategy for the isolation of adipose-derived stem cells:
      minimally manipulated adipose-derived stem cells for more rapid and safe stem
      cell therapy.
AB  - Adipose-derived stem cells are an ideal mesenchymal stem cell population for
      regenerative medical application. The isolation procedure is performed by
      mechanical isolation under a laminar air flow bench without using serum or animal
      derived reagents; cells were characterized by flow cytometric analysis. Cell
      availability is improved compared with enzymatic digestion procedures. The
      adipose-derived stem cell mechanical isolating procedure presented here is
      easier, safer, cheaper, and faster than traditional currently performed enzymatic
      procedures.

PMID- 24867724
TI  - Nerve conduits for peripheral nerve surgery.
AB  - Autologous nerve grafts are the current criterion standard for repair of
      peripheral nerve injuries when the transected nerve ends are not amenable to
      primary end-to-end tensionless neurorrhaphy. However, donor-site morbidities such
      as neuroma formation and permanent loss of function have led to tremendous
      interest in developing an alternative to this technique. Artificial nerve
      conduits have therefore emerged as an alternative to autologous nerve grafting
      for the repair of short peripheral nerve defects of less than 30 mm; however,
      they do not yet surpass autologous nerve grafts clinically. A thorough
      understanding of the complex biological reactions that take place during
      peripheral nerve regeneration will allow researchers to develop a nerve conduit
      with physical and biological properties similar to those of an autologous nerve
      graft that supports regeneration over long nerve gaps and in large-diameter
      nerves. In this article, the authors assess the currently available nerve
      conduits, summarize research in the field of developing these conduits, and
      establish areas within this field in which further research would prove most
      beneficial.

PMID- 24867725
TI  - Discussion: The surgical correction of Pierre Robin sequence: mandibular
      distraction osteogenesis versus tongue-lip adhesion.

PMID- 24867726
TI  - Discussion: The surgical correction of Pierre Robin sequence: mandibular
      distraction osteogenesis versus tongue-lip adhesion.

PMID- 24867727
TI  - Outcomes of cleft palatal repair for internationally adopted children.
AB  - BACKGROUND: Families in the United States adopted approximately 230,000 foreign
      born children over the past two decades. Age at adoption and the presence of a
      cleft palate impact speech and language development. The authors' purpose is to
      document speech outcome after palatal closure in internationally adopted
      children. METHODS: The authors reviewed internationally adopted children with
      cleft lip-cleft palate or cleft palate who had two-flap palatoplasty from 1987 to
      2010. Data collected included date of birth, cleft palatal type, age at
      palatoplasty, palatal fistula, postoperative speech assessment, and need for
      secondary surgery. RESULTS: The authors identified 55 children adopted with
      unrepaired cleft palate. Palatal types were Veau I (n = 1), II (n = 1), III (n =
      37), or IV (n = 16). Median age at palatoplasty was 25.6 +/- 11.8 months; palatal
      fistula occurred in five patients (9 percent). Speech outcome was successful in
      28 patients (51 percent), whereas a secondary operation was recommended for 27
      patients (49 percent). Need for a secondary operation was independent of palatal
      type (p = 0.6). Children who required a pharyngeal flap were significantly older
      at the time of palatoplasty compared with those who did not (p = 0.009). There
      was a significant association between increasing age at palatoplasty and need for
      a secondary operation (OR, 1.07; 95 percent CI, 1.01 to 1.13; p = 0.01).
      Pharyngeal flap significantly improved speech (p < 0.001). CONCLUSIONS:
      International adoption with late palatoplasty can result in disordered speech.
      Velopharyngeal insufficiency is associated with increasing age at palatoplasty.
      The authors recommend palatoplasty and speech therapy soon after adoption.
      CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

PMID- 24867728
TI  - An evaluation of complications, revisions, and long-term aesthetic outcomes in
      nonsyndromic metopic craniosynostosis.
AB  - BACKGROUND: The authors evaluated the complications, revisions, and long-term
      aesthetic outcomes of patients with isolated metopic synostosis. METHODS: A
      retrospective chart review was performed on consecutive metopic craniosynostosis
      patients treated from June of 1987 to June of 2012 at The Children's Hospital of
      Philadelphia. Patient demographics, operative details, and postoperative data
      were collected. Outcomes were reported as Whitaker classification and
      postoperative clinical characteristics assessed before additional interventions.
      Reoperation in patients with greater than 5 years of follow-up was noted.
      Appropriate statistical analyses were applied. RESULTS: From 1987 to 2012, 178
      patients underwent surgical correction of isolated metopic craniosynostosis, and
      147 met inclusion criteria. Average age at surgery was 0.83 year (range, 0.3 to
      4.7 years); average follow-up was 5.8 years (range, 1.0 to 17.8 years). There
      were 13 surgical complications (8.8 percent), three major (2.0 percent), and 10
      minor (6.8 percent). At follow-up, 67 patients (56.8 percent) were classified as
      Whitaker class I, six (5.1 percent) as class II, 43 (36.4 percent) as class III,
      and two (1.7 percent) as class IV. Patients with greater than 5 years' follow-up
      (n = 57) were more likely to have temporal hollowing (OR, 2.9; 95 percent CI, 1.2
      to 7.3; p = 0.021), lateral orbital retrusion (OR, 4.9; 95 percent CI, 1.9 to
      12.7; p = 0.001), and Whitaker class III or IV classification (OR, 4.0; 95
      percent CI, 1.5 to 10.6; p = 0.006) compared with those with less than 5 years'
      follow-up. CONCLUSION: This study reports low complication and reoperation rates
      in the treatment of isolated metopic craniosynostosis, but demonstrates a clear
      trend toward worsening aesthetic outcomes over time. CLINICAL QUESTION/LEVEL OF
      EVIDENCE: Therapeutic, IV.

PMID- 24867729
TI  - Reduction of pulmonary complications and hospital length of stay with a clinical
      care pathway after head and neck reconstruction.
AB  - BACKGROUND: Pulmonary complications are common after major head and neck
      oncologic surgery with microsurgical reconstruction and are associated with
      increased mortality and morbidity. Clinical care pathways are evidence-based
      tools that reduce unnecessary practice variation and ultimately improve patient
      outcomes. In this study, the authors evaluate the effectiveness of a
      comprehensive care pathway on reducing postoperative pulmonary complications and
      hospital length of stay in patients undergoing major head and neck carcinoma
      resection with free flap reconstruction. METHODS: Fifty-five consecutive patients
      treated according to a prescribed postoperative clinical care pathway were
      compared to a historical cohort of patients treated before the implementation of
      the pathway. The incidence of pulmonary complications, hospital length of stay,
      and free flap survival were compared between the control and intervention groups.
      RESULTS: Patients on the clinical care pathway had 32.5 percent fewer pulmonary
      complications (p < 0.0001) and 7.4 days' shorter hospital length of stay (p =
      0.0007) than patients not on the postoperative pathway. There was no significant
      difference in the rate of flap reoperation. CONCLUSIONS: A multidisciplinary,
      comprehensive, clinical care pathway for patients undergoing major head and neck
      surgery with microsurgical reconstruction is effective in reducing postoperative
      pulmonary complications and hospital length of stay. The postoperative pathway is
      safe in this patient population and should be considered for adoption into
      clinical practice. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

PMID- 24867730
TI  - Proximal peroneal perforator in dual-skin paddle configuration of fibula free
      flap for composite oral reconstruction.
AB  - BACKGROUND: Composite defects of the oral cavity are often the result of trauma
      or advanced-stage tumor extirpation. The resultant deformity frequently requires
      a three-dimensional reconstruction of bone and soft-tissue. The fibula free flap
      is the preferred method of reconstruction, with various modifications focused on
      providing supplemental soft-tissue coverage. The objective of this study was to
      ascertain both anatomic and clinical data regarding the proximal peroneal
      perforator and its contribution to the evolution of the fibula free flap.
      METHODS: Ten cadaver lower extremities were dissected to isolate the most
      proximal perforator supplying skin over the proximal lateral lower leg. Data were
      recorded regarding perforator presence, location, and course. Furthermore, review
      of clinical cases in which the proximal perforator was used in fibula free flap
      design was performed for operative data collection. RESULTS: Cadaveric
      dissections revealed the proximal perforator to be present in 90 percent of
      specimens. Most commonly, the perforator, originating from the peroneal artery,
      traveled a short intramuscular course through the soleus muscle prior to
      supplying the overlying skin. In all clinical cases, the perforator was easily
      located with Doppler prior to incision, and there were no cases of flap failure
      or skin paddle loss. Flap inset was found to be optimal in all cases, with no
      tethering or undue tension. CONCLUSIONS: The proximal peroneal perforator was
      found to be anatomically reliable and clinically useful in composite oral cavity
      reconstruction following tumor removal. The gained separation between skin
      paddles allows for greater versatility in flap design and inset. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 24867731
TI  - Demystifying the U.S. Food and Drug Administration: I. Understanding agency
      structure and function.
AB  - The U.S. Food and Drug Administration is the government agency responsible for
      oversight of the safety and efficacy of pharmaceuticals and devices, including
      biologics and devices that combine biologics with other materials. Within the
      U.S. Food and Drug Administration, the Center for Biologics Evaluation and
      Research is specifically responsible for the evaluation and approval of
      biological products. This department of the U.S. Food and Drug Administration has
      a series of mechanisms in place to aid researchers in the process of developing
      new biologics. This article outlines the study phases involved in developing new
      biologics and how the Center for Biologics Evaluation and Research and
      investigators can work together to facilitate this process. It also discusses
      issues specific to biologics that have been encountered in the past and that
      investigators should consider when developing and obtaining approval for new
      biologics. The equivalent center within the U.S. Food and Drug Administration for
      approving medical devices is the Center for Devices and Radiological Health. The
      equivalent process of development and approval of medical devices is similarly
      discussed. Finally, essential contacts for investigators within the Center for
      Biologics Evaluation and Research and the Center for Devices and Radiological
      Health are provided.

PMID- 24867732
TI  - Journal impact factor versus the evidence level of articles published in plastic
      surgery journals.
AB  - BACKGROUND: The aim of this study was to assess the correlation between impact
      factor and the level of evidence of articles in plastic surgery journals.
      METHODS: The four plastic surgery journals with the top impact factors in 2011
      were selected. Articles were selected using the PubMed database between January 1
      and December 31, 2011. The journal evidence index was calculated by dividing the
      number of randomized clinical trials by the total number of articles published in
      the specific journal, multiplied by 100. This index was correlated to the impact
      factor of the journal and compared with the average of the other journals. Two
      investigators independently evaluated each journal, followed by a consensus and
      assessment of the interexaminer concordance. The kappa test was used to evaluate
      the concordance between the two investigators and Fisher's exact test was used to
      evaluate which journal presented the highest number of randomized clinical
      trials. RESULTS: The journal evidence index values were as follows: Plastic and
      Reconstructive Surgery, 1.70; Journal of Plastic, Reconstructive and Aesthetic
      Surgery, 0.40; Aesthetic Plastic Surgery, 0.56; and Annals of Plastic Surgery,
      0.35. The impact factors of these journals in 2011 were as follows: Plastic and
      Reconstructive Surgery, 3.382; Journal of Plastic, Reconstructive and Aesthetic
      Surgery, 1.494; Aesthetic Plastic Surgery, 1.407; and Annals of Plastic Surgery,
      1.318. After consensus, the quantity of adequate studies was low and similar
      between these journals; only the journal Plastic and Reconstructive Surgery
      showed a higher journal evidence index. CONCLUSIONS: The journal Plastic and
      Reconstructive Surgery exhibited the highest journal evidence index and had the
      highest impact factor. The number of adequate articles was low in all of the
      assessed journals.

PMID- 24867733
TI  - Regenerative medicine and the future of plastic surgery.

PMID- 24867734
TI  - Direct-to-implant single-stage immediate breast reconstruction with acellular
      dermal matrix: predictors of failure.
AB  - BACKGROUND: Direct-to-implant single-stage immediate breast reconstruction using
      acellular dermal matrix is a cost-effective alternative to two-stage expander
      implant reconstruction. The purpose of this study was to identify predictors of
      direct-to-implant single-stage immediate breast reconstruction failure, defined
      as need for early (<=6 months) revision surgery. METHODS: The authors conducted a
      retrospective cohort study of all patients with direct-to-implant single-stage
      immediate breast reconstruction in 2010 and 2011 at three University of British
      Columbia hospitals. Data were compared between successful and failed single-stage
      reconstructions. Predictors of failure were identified using multivariate
      logistic regression. Patient demographics and complications were compared to a
      random sample of control patients with two-stage alloplastic reconstruction
      without acellular dermal matrix. RESULTS: Of 164 breasts that underwent direct-to
      implant single-stage immediate breast reconstruction, 52 (31.7 percent) required
      early revision. Increasing breast cup size was the only significant predictor of
      early revision compared with bra size A (OR for bra size B, 4.86; C, 4.96; D,
      6.01; p < 0.05). Prophylactic mastectomies showed a trend toward successful
      single stage (OR, 0.47; p = 0.061), whereas smoking history trended toward
      failure (OR, 1.79; p = 0.065). Mastectomy flap necrosis was significantly higher
      in direct-to-implant single-stage immediate reconstruction cases compared to two
      stage controls. CONCLUSIONS: Direct-to-implant breast reconstruction can be
      reliably performed in a single stage in patients with small breast size.
      Increasing breast cup size confers a higher chance of early revision. A two-stage
      approach may be more cost-effective in larger breasted patients. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Risk, III.

PMID- 24867735
TI  - The differential impact of plastic surgery subspecialties on the financial
      performance of an academic clinical practice.
AB  - BACKGROUND: In an academic center, plastic surgery provides multiple important
      and distinct services. Limited data exist on how each service affects a
      department clinically and financially. METHODS: All new patient consultations and
      surgical cases between 2004 and 2012 were reviewed. Conversion rates from
      consultation to surgery and relative value units were calculated. Professional
      and facility revenues, costs, and net income were ascertained. These measures
      were compared between different subspecialties. RESULTS: A total of 12,020 new
      patient consultations and 5741 surgical cases were reviewed. Total growth in
      consultations was greatest for breast reconstruction (396.8 percent), followed by
      aesthetic (83.8 percent), oncology (12.9 percent), general (-16.9 percent), and
      burn/trauma (-75.0 percent). The conversion rate from consultation to surgery was
      highest in breast reconstruction (57.0 +/- 3.1 percent) and oncology (56.9 +/-
      6.6 percent), followed by burn/trauma (47.0 +/- 6.8 percent), general (46.1 +/-
      3.5 percent), and aesthetic (37.0 +/- 4.8 percent). Total growth in professional
      net income was greatest for breast reconstruction (1241.4 percent), followed by
      oncology (378.4 percent), general (159.7 percent), aesthetic (130.5 percent), and
      burn/trauma (-20.9 percent). Total growth in facility net income was greatest for
      breast reconstruction (7619.5 percent), followed by oncology (2648.0 percent),
      aesthetic (432.3 percent), general (283.3 percent), and burn/trauma (108.7
      percent). CONCLUSIONS: Breast reconstruction exhibited the greatest growth in
      consultations, and oncologic consultations demonstrated the highest consultation
      to-surgery conversion rate. The higher consultation volume and conversion rate
      associated with breast reconstruction resulted in greater financial gains for
      both the department and the hospital. These findings may be of utility in the
      development of academic plastic surgery programs.

PMID- 24867736
TI  - Chimeric autologous costal cartilage graft to prevent warping.
AB  - BACKGROUND: Carved autologous costal cartilage is widely used in different
      rhinoplasty procedures because of its availability and proven advantages.
      However, the usefulness of rib grafts is limited by warping postoperatively. The
      chimeric autologous costal cartilage graft is proposed. "Chimeric" means the
      combining of two different tissues (bone and cartilage in this case) to make a
      single dorsal onlay graft. METHODS: From October of 2010 to August of 2013, 31
      patients underwent rhinoplasty or nasal reconstruction with costal cartilage
      graft using the chimeric autologous costal graft method. There were 14 men and 17
      women, with ages ranging from 20 to 66 years (average, 33 years). Of the 31
      patients, there were 12 with congenital nasal deformities, six with previous
      nasal trauma, eight with aesthetic rhinoplasty (four with primary rhinoplasty and
      four with secondary rhinoplasty), and five with nasal deformities after tumor
      extirpation. Patients' profiles were documented and photographed. The outcomes
      were assessed by three plastic surgeons. RESULTS: Follow-up for all patients was
      4 to 30 months (average, 14 months). No cartilage warping was noted during the
      follow-up period. Two patients suffered from minor infection 2 weeks
      postoperatively. The average operative time for carving cartilage was 10 minutes.
      The overall average time of making a chimeric autologous costal onlay graft added
      approximately 20 minutes to the original method. CONCLUSION: From the clinical
      observation of all patients during the follow-up period, the chimeric autologous
      costal cartilage graft was shown to be effective for preventing cartilage
      warping. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 24867737
TI  - Body contouring surgery after bariatric surgery: a study of cost as a barrier and
      impact on psychological well-being.
AB  - BACKGROUND: Body-contouring surgery can be a solution to excess skin folds
      following bariatric surgery. Many patients desire body-contouring surgery, but
      the cost of the procedure may be a limiting factor. This study aims to examine
      barriers to access and to compare socioeconomic variables and psychological
      variables between bariatric surgery patients who have undergone body contouring
      and those who have not. METHODS: In this cross-sectional study, a questionnaire
      packet was administered to (1) patients who underwent bariatric but not body
      contouring surgery and (2) patients who underwent both. The questionnaire
      included perceived barriers to body-contouring surgery, socioeconomic barriers,
      measures of anxiety (Generalized Anxiety Disorder seven-item scale), depression
      (Patient Health Questionnaire nine-item scale), and quality of life (Short Form
      36). RESULTS: Among the 58 study participants, 93.1 percent reported having
      excess skin folds. Of this sample, 95.4 percent desired body-contouring surgery,
      and the majority (87.8 percent) of this subsample identified cost as the major
      barrier to access. Mean scores on the Generalized Anxiety Disorder scale (6.08 +/
      5.97 versus 3.50 +/- 3.10; p = 0.030) and the Patient Health Questionnaire (6.40
      +/- 6.77 versus 2.40 +/- 2.37; p = 0.002) were significantly higher for the
      bariatric surgery group versus bariatric surgery plus body contouring group.
      Patients in the latter group had significantly higher Short Form-36 physical
      health component scores (56.80 +/- 4.88 versus 49.57 +/- 8.25; p = 0.010).
      CONCLUSIONS: Bariatric surgery patients who desire body-contouring surgery
      perceive cost as a major barrier. Patients undergoing body-contouring surgery may
      experience improved physical quality of life but not mental quality of life;
      however, body-contouring surgery may improve aspects of depression and anxiety.

PMID- 24867738
TI  - Trends and drivers of the aesthetic market during a turbulent economy.
AB  - BACKGROUND: Aesthetic procedures are significant sources of revenue for plastic
      surgeons. With the popularity of nonsurgical aesthetic procedures, many plastic
      surgeons question how to best tailor their aesthetic practice. METHODS: Revenue
      generated from surgical and minimally invasive aesthetic procedures performed in
      the United States between 2000 and 2011 was calculated from the American Society
      of Plastic Surgeons' annual reports. Regression analysis was performed against
      six commonly cited economic indicators. RESULTS: In 2011, revenue from minimally
      invasive procedures increased from $3.0 billion to $5.7 billion (90 percent
      growth), whereas revenue from surgical procedures decreased from $6.6 billion to
      $6.0 billion (10 percent decline). Between 2000 and 2011, minimally invasive
      procedure market share grew from 30 percent to nearly 50 percent. Linear
      regression analysis revealed significant correlations between surgical procedure
      revenue and indicators of macroeconomic climate: Dow Jones Industrial Average (R
      = 0.72; p < 0.01), Standard & Poor's 500 Index (R = 0.64, p < 0.05), and
      unemployment rate (R = -0.81; p < 0.001). Minimally invasive procedure revenue
      was significantly correlated with indicators related to microeconomic decision
      trends: disposable income per capita (R = 0.93; p < 0.001), real gross domestic
      product per capita (R = 0.88; p < 0.001), and home price index (R = 0.63; p <
      0.05). No economic indicator in this study was found to be significantly
      correlated with both surgical and minimally invasive revenue. CONCLUSION: Despite
      economic turbulence, minimally invasive procedures are the most rapidly growing
      source of revenue and are poised to be the dominant source of revenue in the
      aesthetic market.

PMID- 24867739
TI  - Evaluation of nanofiber-based polyglycolic acid scaffolds for improved
      chondrocyte retention and in vivo bioengineered cartilage regeneration.
AB  - BACKGROUND: In conventional studies on the regeneration of auricle-shaped
      cartilage in autogenous models using large animals, there were problems with the
      cartilage regeneration induction capacity and long-term retention of geometric
      shape. In this study, the authors sought to improve on outcome in these regards:
      a nonwoven fabric of polyglycolic acid was developed through nanotechnology, and
      the effect of nanofiber diameter on in vitro cell-seeding efficiency and the in
      vivo response after implantation in an autogenous large-animal model were
      evaluated. METHODS: Canine chondrocytes were isolated and seeded onto
      polyglycolic acid fabric ranging from 0.5 to 20 MUm in average diameter. Cell
      seeding efficiency was highest for mid-range polyglycolic acid fibers (average
      diameter, 0.8, 3.0, and 7.0 MUm). Flat and auricle-shaped scaffolds were
      constructed using polypropylene structural support, sandwiching a nonwoven
      polyglycolic acid fabric that contained autogenous chondrocytes together with
      basic fibroblast growth factor-laden particles and an exterior fibrin sealant.
      Scaffolds were then implanted autogenously and evaluated at 5 and 20 weeks.
      RESULTS: Biomechanical strength was optimal for polyglycolic acid fiber diameters
      of 0.8 to 3.0 MUm. Optimal cell maintenance and neocartilage response were seen
      with polyglycolic acid fiber diameters in the same mid-range for nanofiber
      constructs. CONCLUSION: These findings demonstrate the potential for nanoscale
      modulation of auricle-shaped cartilage regeneration in a large-animal model.

PMID- 24867740
TI  - Hand tumors: II. Benign and malignant bone tumors of the hand.
AB  - The incidence of both benign and malignant bone tumors arising in the hand is
      relatively low in comparison with other locations. Although the overwhelming
      majority of these tumors are benign, even benign tumors can be locally
      destructive and compromise hand function. Intralesional tumor excision is the
      most appropriate surgical intervention for many benign bone tumors of the hand;
      however, destructive or malignant tumors may require wide local excision or even
      amputation to achieve complete tumor eradication. The purpose of this review
      article is to provide an overview of the pertinent benign and malignant bone
      tumors that may be encountered by hand surgeons. Clinical presentation,
      radiographic features, recommended workup, and available treatment options are
      all reviewed.

PMID- 24867741
TI  - Split cranial bone grafting in children younger than 3 years old: debunking a
      surgical myth.
AB  - BACKGROUND: In cranioplasty patients split cranial bone provides excellent
      structural support and fundamentally "replaces like with like." However,
      traditional teaching in craniofacial surgery is that cranial bone cannot be split
      before the age of 3 years because of the lack of diploic space. The authors have
      found this not to be the case and describe their experience with splitting
      cranial bone in children with craniosynostosis younger than 3 years. METHODS: The
      authors completed a retrospective review of 418 cranioplasties performed between
      1997 and 2013 by a single surgeon on patients younger than 3 years with syndromic
      and nonsyndromic craniosynostosis. Average patient age at the time of the
      procedure was 328 days. The youngest patient was 58 days old. RESULTS: Of the 418
      cranial procedures performed in this study, cranial bone could be split and used
      as bone graft in every case. Although the presence of Luckenschadel prevented a
      complete split of the inner table from the outer table of the bone flap, split
      cranial bone grafting could still be performed, providing significant grafting
      material to foster reconstruction. No complications from split cranial harvest
      were observed. CONCLUSIONS: Contrary to popular belief and the misconception
      perpetuated by the Plastic Surgery In-Service Examination, the cranium of
      children younger than 3 years can indeed be safely and predictably split between
      the inner and outer cortex. This important finding provides the craniofacial
      surgeon with a valuable, expanded source of rigid bone for cranial vault
      remodeling in the pediatric patient population. CLINICAL QUESTION/LEVEL OF
      EVIDENCE: Therapeutic, IV.

PMID- 24867742
TI  - Examining factors associated with oral health-related quality of life for youth
      with cleft.
AB  - BACKGROUND: Patient-reported quality-of-life outcomes in cleft lip-cleft palate
      treatment are critical for evidence-based care. Scant data exist analyzing
      treatment from the patient's perspective. The authors examined the
      interrelationship among variables associated with oral health-related quality of
      life among youth with cleft. METHODS: As part of an ongoing longitudinal study,
      clinical evaluations and research questionnaire packets were completed before
      surgical recommendations were made (baseline). Participants completed the Child
      Oral Health Impact Profile, a validated oral health-related quality-of-life
      measure for children with cleft. During the baseline clinical evaluations,
      plastic surgeons determined whether surgical interventions were recommended
      within the year (expert determination represents a greater degree of current
      clinical need). General linear models incorporating surgical recommendation,
      gender, and age were fit for each subscale of and for the total Child Oral Health
      Impact Profile. Significant interaction terms were evaluated for their effect on
      the subscale. RESULTS: Baseline assessments were obtained from 1200 participants
      (mean, 11.8 years; 57 percent male). Participants with a surgical recommendation
      had lower quality of life on all but the self-esteem subscale compared with those
      without a surgical recommendation (p < 0.002). Two subscales had statistically
      significant age-sex interactions (p < 0.003), whereas another subscale had a
      statistically significant surgery by sex interaction term (p = 0.027).
      CONCLUSIONS: Overall, youth for whom surgery is currently recommended had lower
      oral health-related quality-of-life scores on the Child Oral Health Impact
      Profile Total scale than those with no surgical recommendation; older female
      subjects had lower quality-of-life scores than male subjects. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Risk, II.

PMID- 24867744
TI  - Facial synkinesia before and after surgical reanimation of the paralyzed face.
AB  - BACKGROUND: Facial synkinesia is a common sequela of facial palsy, affecting 15
      to 20 percent of patients. The rate of postoperative synkinesia after facial
      reanimation is not clearly established. The severity and type of synkinesia
      determine the degree of clinical relevance. METHODS: One hundred sixty-seven
      patients with facial palsy were included in this retrospective cohort study.
      Three-dimensional video analysis of facial movements was performed preoperatively
      and 18 months after facial reanimation. The severity of synkinesia was rated
      subjectively on a four-degree severity scale. Objective three-dimensional
      analysis of synkinesia was performed on patients with 18-month follow-up times.
      RESULTS: Preoperatively, 84.4 percent of patients were not affected by
      synkinesia, 9 percent presented with mild synkinesia, 4.2 percent presented with
      moderate synkinesia, and 2.4 percent presented with severe synkinesia.
      Postoperatively, 51 percent of all patients presented with facial synkinesia
      (41.8 percent mild, 17.3 percent moderate, and 1 percent severe synkinesia; some
      patients had more than one type). Patients treated with territorially
      differentiated gracilis muscle transplantation were most frequently affected
      (69.8 percent), followed by patients treated with gracilis muscle transplantation
      in combination with temporalis muscle transposition to the eye (51.8 percent).
      Oculo-oral synkinesia was the most frequent form of synkinesia. CONCLUSIONS:
      After surgical reanimation of the paralyzed face, half of the patients presented
      with synkinesia. The majority of patients developed mild or moderate forms of
      synkinesia; therefore, the clinical relevance of synkinesia has to be seen in the
      context of total facial function. Because of the high prevalence of synkinesia,
      it should be documented and addressed in patients undergoing facial reanimation.
      CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 24867743
TI  - Brain electrophysiology reveals intact processing of speech sounds in
      deformational plagiocephaly.
AB  - BACKGROUND: The prevalence of deformational plagiocephaly has risen dramatically
      in recent years, now affecting 15 percent or more of infants. Prior research
      using developmental scales suggests that these children may be at elevated risk
      for developmental delays. However, the low positive predictive value of such
      instruments in identifying long-term impairment, coupled with their poor
      reliability in infants, warrants the development of methods to more precisely
      measure brain function in craniofacial patients. Event-related potentials offer a
      direct measure of cortical activity that is highly applicable to young
      populations and has been implemented in other disorders to predict long-term
      cognitive functioning. The current study used event-related potentials to
      contrast neural correlates of auditory perception in infants with deformational
      plagiocephaly and typically developing children. METHODS: Event-related
      potentials were recorded while 16 infants with deformational plagiocephaly and 18
      nonaffected controls passively listened to speech sounds. Given prior research
      suggesting their association with subsequent functioning, analyses focused on the
      P150 and N450 event-related potential components. RESULTS: Deformational
      plagiocephaly patients and normal controls showed comparable cortical responses
      to speech sounds at both auditory event-related potential components.
      CONCLUSIONS: Children with deformational plagiocephaly demonstrate neural
      responses to language that are consistent with normative expectations and
      comparable to those of typical children. These results indicate that head shape
      deformity secondary to supine sleep is not associated with impairments in
      auditory processing. The applicability of the current methods in early infancy
      suggests that electrophysiologic brain recordings represent a promising method of
      monitoring brain development in children with cranial disorders. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Risk, II.

PMID- 24867745
TI  - Cleft palate repair and velopharyngeal dysfunction.
AB  - LEARNING OBJECTIVES: After studying this article, the participant should be able
      to: (1) Describe the technical details common to all cleft palate repairs that
      optimize outcomes and minimize complications. (2) Explain the subjective and
      objective evaluation of speech in children with cleft palate. (3) Practice with
      an increased awareness of the management of complications associated with cleft
      palate repair. (4) Design a treatment plan for velopharyngeal dysfunction.
      SUMMARY: Goals of a successful cleft palate repair include separation of the oral
      and nasal components without fistula, achieving sufficient velar length, and
      creating functional transverse orientation of the levator muscle sling. A number
      of techniques have been described to achieve these goals, but they all have the
      following technical details in common: elevation of oral mucosal flaps based on
      the greater palatine arteries, tension free nasal lining mobilization, and
      functional intervelar muscle dissection. After palate repair, speech evaluation
      needs to be performed by an objective interdisciplinary team following a
      standardized protocol. Identification of velopharyngeal insufficiency secondary
      to an incompetent nasopharyngeal port will necessitate secondary speech surgery.
      These secondary techniques include pharyngeal flaps, soft palate lengthening, or
      pharyngeal sphincters, which should be tailored to optimize speech, while
      minimizing the risk of obstructive sleep apnea.

PMID- 24867746
TI  - The ever-changing role of biofilms in plastic surgery.
AB  - The goal of this article is to present a brief background of biofilms and how
      they pertain to plastic surgery. Of particular interest are how biofilms affect
      breast prosthesis and their subsequent complications. The authors also present
      information on how biofilms are involved in soft-tissue filler complications.
      After a brief review of the pathophysiology of biofilms and their effect on
      plastic surgery, the authors propose a revised algorithm to assist in guiding the
      plastic surgeon when faced with complications that involve biofilms that involves
      more rapid diagnosis and treatment using polymerase chain reaction technology.
      This article is a review of recent literature.

PMID- 24867747
TI  - On facial asymmetry and self-perception.
AB  - Self-perception has been an enduring human concern since ancient times and
      remains a significant component of the preoperative and postoperative
      consultation. Despite modern technological attempts to reproduce the first-hand
      experience, there is no perfect substitute for human, stereoscopic, three
      dimensional vision in evaluating appearance. Nowadays, however, the primary tools
      available to a patient for examining his or her own appearance, particularly the
      face, are photographs and mirrors. Patients are often unaware of how cameras and
      photographs can distort and degrade image quality, leading to an inaccurate
      representation of true appearance. Everyone knows that mirrors reverse an image,
      left and right, and most people recognize their own natural facial asymmetry at
      some level. However, few realize that emotions are not only expressed unequally
      by the left and right sides of the face but also perceived unequally by others.
      The impact and effect of this "facedness" is completely reversed by mirrors,
      potentially creating a significant discrepancy between what a patient perceives
      of himself or herself and what the surgeon or other third party sees. This
      article ties together the diverse threads leading to this problem and suggests
      several ways of mitigating the issue through technology and patient counseling.

PMID- 24867748
TI  - Breast reconstruction in the morbidly obese patient: assessment of 30-day
      complications using the 2005 to 2010 national surgical quality improvement
      program data sets.

PMID- 24867749
TI  - A matched cohort study of superomedial pedicle vertical scar breast reduction
      (100 breasts) and traditional inferior pedicle wise-pattern reduction (100
      breasts): an outcomes study over 3 years.

PMID- 24867750
TI  - Reply: A matched cohort study of superomedial pedicle vertical scar breast
      reduction (100 breasts) and traditional inferior pedicle wise-pattern reduction
      (100 breasts): an outcomes study over 3 years.

PMID- 24867751
TI  - A prospective analysis of 100 consecutive lymphovenous bypass cases for treatment
      of extremity lymphedema.

PMID- 24867752
TI  - Reply: A prospective analysis of 100 consecutive lymphovenous bypass cases for
      treatment of extremity lymphedema.

PMID- 24867753
TI  - Adipose stromal vascular fraction isolation: a head-to-head comparison of four
      commercial cell separation systems.

PMID- 24867754
TI  - Reply: Adipose stromal vascular fraction isolation: a head-to-head comparison of
      four commercial cell separation systems.

PMID- 24867755
TI  - True and "choke" anastomoses between perforator angiosomes: part I. Anatomical
      location.

PMID- 24867756
TI  - Reply: True and "choke" anastomoses between perforator angiosomes: part I.
      Anatomical location.

PMID- 24867757
TI  - Current concepts in the evaluation and treatment of mallet finger injury.

PMID- 24867758
TI  - A new recipient artery for reconstruction of soft-tissue defects in the lower
      limb with a free anterolateral thigh flap: the reversed descending branch of the
      lateral femoral circumflex artery.

PMID- 24867759
TI  - Reply: A new recipient artery for reconstruction of soft-tissue defects in the
      lower limb with a free anterolateral thigh flap: the reversed descending branch
      of the lateral femoral circumflex artery.

PMID- 24867760
TI  - The assassination of John F. Kennedy: revisiting the medical data.

PMID- 24867761
TI  - Reply: The assassination of John F. Kennedy: revisiting the medical data.

PMID- 24867762
TI  - Biopsy of internal mammary chain lymph nodes found incidentally during autologous
      breast reconstruction.

PMID- 24867763
TI  - Management of the post-breast reconstruction "hyperanimation deformity".

PMID- 24867764
TI  - The neutral window: a tool to simplify nipple-areola complex color matching.

PMID- 24867765
TI  - An alternative contrast medium for computed tomographic angiography: gadolinium.

PMID- 24867766
TI  - Combined double-opposing Z-plasty and posterior pharyngeal flap to address severe
      velopharyngeal dysfunction.

PMID- 24867767
TI  - A case of a survivor to a through-and-through head gunshot wound following
      Russian roulette.

PMID- 24867768
TI  - 28 years' follow-up of bitten-off nose replantation performed in a 9-year-old
      girl.

PMID- 24867769
TI  - Real-time free flap monitoring using a standard video camera: a lower cost and
      simpler option?

PMID- 24867770
TI  - Electronic cigarettes: have you asked your patients about vaping?

PMID- 24867771
TI  - The cost of medical tourism: penny-wise and pound-foolish?

PMID- 24867773
TI  - Peri-procedural management of anti-platelets and anticoagulation in patients
      undergoing MitraClip procedure.
AB  - The MitraClip device was recently approved by the FDA for the management of
      severe degenerative mitral regurgitation in patients considered to be high risk
      for surgical repair or replacement of the mitral valve. The management of anti
      platelet and anticoagulant therapy before, during, and after the MitraClip
      placement is not well defined given the lack of evidence from large randomized
      trials. In this paper, we propose practical management guidelines for using these
      agents. 

PMID- 24867774
TI  - Psoriatic arthritis: Mary Stults Sherman, a forgotten figure in its history.
AB  - Mary Sherman was an American orthopedic surgeon who in 1952 published one of the
      earliest descriptions of psoriatic arthritis in the English literature. In a time
      when the general consensus by American rheumatologists was that there was no
      sufficient evidence to consider psoriatic arthritis as a distinct entity, Mary
      Sherman argued otherwise. Her work provided clinical, pathological, and
      therapeutic evidence in support of its distinctiveness as a unique disorder
      separate from rheumatoid arthritis. 

PMID- 24867772
TI  - The association between spinal cord trauma-sensitive miRNAs and pain sensitivity,
      and their regulation by morphine.
AB  - Increased pain sensitivity is a common sequela to spinal cord injury (SCI).
      Moreover, drugs like morphine, though critical for pain management, elicit pro
      inflammatory effects that exacerbate chronic pain symptoms. Previous reports
      showed that SCI results in the induction and suppression of several microRNAs
      (miRNAs), both at the site of injury, as well as in segments of the spinal cord
      distal to the injury site. We hypothesized that morphine would modulate the
      expression of these miRNAs, and that expression of these SCI-sensitive miRNAs may
      predict adaptation of distal nociceptive circuitry following SCI. To determine
      whether morphine treatment further dysregulates SCI-sensitive miRNAs, their
      expression was examined by qRT-PCR in sham controls and in response to vehicle
      and morphine treatment following contusion in rats, at either 2 or 15 days post
      SCI. Our data indicated that expression of miR1, miR124, and miR129-2 at the
      injury site predicted the nociceptive response mediated by spinal regions distal
      to the lesion site, suggesting a molecular mechanism for the interaction of SCI
      with adaptation of functionally intact distal sensorimotor circuitry. Moreover,
      the SCI-induced miRNA, miR21 was induced by subsequent morphine administration,
      representing an alternate, and hitherto unidentified, maladaptive response to
      morphine exposure. Contrary to predictions, mRNA for the pro-inflammatory
      interleukin-6 receptor (IL6R), an identified target of SCI-sensitive miRNAs, was
      also induced following SCI, indicating dissociation between miRNA and target gene
      expression. Moreover, IL6R mRNA expression was inversely correlated with
      locomotor function suggesting that inflammation is a predictor of decreased
      spinal cord function. Collectively, our data indicate that miR21 and other SCI
      sensitive miRNAs may constitute therapeutic targets, not only for improving
      functional recovery following SCI, but also for attenuating the effects of SCI on
      pain sensitivity.

PMID- 24867775
TI  - Biomimetic synthesis of (+)-ledene, (+)-viridiflorol, (-)-palustrol, (+)
      spathulenol, and psiguadial A, C, and D via the platform terpene (+)
      bicyclogermacrene.
AB  - (+)-Bicyclogermacrene is a strained bicyclic and common sesquiterpene found in
      several essential oils. A short and good yielding synthesis of bicyclogermacrene
      proceeding in seven steps is reported. This terpene is used as key platform
      intermediate for a biomimetic access to several aromadendrene sesquiterpenoids,
      such as ledene, viridiflorol, palestrol, and spathulenol. Furthermore,
      bicyclogermacrene is shown to be the terpene component in the synthesis of the
      meroterpenoids psiguadial A, C, and D. 

PMID- 24867776
TI  - Effect of oleic acid on the levels of eight metal ions in human hepatoma SMMC
      7721 cells.
AB  - Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver
      disease. Its incidence is rising worldwide. However, no specific therapy has been
      shown to be effective in its treatment. In the present study, the in vitro NAFLD
      model was established in human SMMC-7721 cells by using oleic acid (OA). Then,
      content changes of eight cations, including sodium, magnesium, potassium,
      calcium, iron, copper, zinc, and manganese, were investigated in the experimental
      model. The results showed that OA induced a decrease in magnesium level, while an
      increase in iron one. Additionally, the supplementation of magnesium in the cell
      culture model was studied. It showed that magnesium ameliorated lipid
      accumulation induced by OA. Our results suggest that magnesium could decrease the
      risk of NAFLD and be used as a promising candidate for the treatment of NAFLD. 

PMID- 24867777
TI  - Early versus late preemptive allogeneic hematopoietic cell transplantation for
      relapsed or refractory acute myeloid leukemia.
AB  - Many patients with relapsed or refractory acute myeloid leukemia (AML) do not
      receive allogeneic hematopoietic cell transplantation (alloHCT) because they are
      unable to achieve a complete remission (CR) after reinduction chemotherapy.
      Starting in January 2003, we prospectively assigned patients with AML with high
      risk clinical features to preemptive alloHCT (p-alloHCT) as soon as possible
      after reinduction chemotherapy. High-risk clinical features were associated with
      poor response to chemotherapy: primary induction failure, second or greater
      relapse, and first CR interval <6 months. We hypothesized that any residual
      disease would be maximally reduced at the time of transplant, resulting in the
      best milieu and most lead time for developing a graft-versus-leukemia effect and
      in improved long-term overall survival (OS) without excess toxicity. This
      analysis studied the effect of transplant timing on p-alloHCT in 30 patients with
      high-risk clinical features of 156 consecutive AML patients referred for alloHCT.
      We compared early p-alloHCT within 4 weeks of reinduction chemotherapy before
      count recovery with late p-alloHCT 4 weeks after reinduction chemotherapy with
      count recovery. OS and progression-free survival (PFS) at 2 years were not
      significantly different for early versus late p-alloHCT (OS 23% versus 33%,
      respectively, P > .1; PFS 18% versus 22%, respectively, P > .1). Day 100 and 1
      year transplant-related mortality were similar (33.3% versus 22.2%, P > .1; 44.4%
      versus 42.9%, P > .1, respectively). Preemptive alloHCT allowed 30 patients to be
      transplanted who would normally not receive alloHCT. Clinical outcomes for early
      p-alloHCT are similar to those for late p-alloHCT without excess toxicity. Early
      p-alloHCT is a feasible alternative to late p-alloHCT for maximizing therapy of
      AML that is poorly responsive to induction chemotherapy. 

PMID- 24867778
TI  - Financial burden in recipients of allogeneic hematopoietic cell transplantation.
AB  - Although allogeneic hematopoietic cell transplantation (HCT) is an expensive
      treatment for hematological disorders, little is known about the financial
      consequences for the patients who undergo this procedure. We analyzed factors
      associated with its financial burden and its impact on health behaviors of
      allogeneic HCT recipients. A questionnaire was retrospectively mailed to 482
      patients who underwent allogeneic HCT from January 2006 to June 2012 at the Mayo
      Clinic, to collect information regarding current financial concerns, household
      income, employment, insurance, out-of-pocket expenses, and health and functional
      status. A multivariable logistic regression analysis identified factors
      associated with financial burden and treatment nonadherence. Of the 268
      respondents (56% response rate), 73% reported that their sickness had hurt them
      financially. All patients for whom the insurance information was available
      (missing, n = 13) were insured. Forty-seven percent of respondents experienced
      financial burden, such as household income decreased by >50%, selling/mortgaging
      home, or withdrawing money from retirement accounts. Three percent declared
      bankruptcy. Younger age and poor current mental and physical functioning
      increased the likelihood of financial burden. Thirty-five percent of patients
      reported deleterious health behaviors because of financial constraints. These
      patients were likely to be younger, have lower education, and with a longer time
      since HCT. Being employed decreased the likelihood of experiencing financial
      burden and treatment nonadherence due to concern about costs. A significant
      proportion of allogeneic HCT survivors experience financial hardship despite
      insurance coverage. Future research should investigate potential interventions to
      help at-risk patients and prevent adverse financial outcomes after this life
      saving procedure. 

PMID- 24867780
TI  - Studying the dynamic behaviour of porphyrins as prototype functional molecules by
      scanning tunnelling microscopy close to room temperature.
AB  - Scanning tunnelling microscopy (STM) enables us to directly observe the dynamic
      behaviour of organic molecules on surfaces. While imaging atoms and molecules
      using STM is certainly fascinating by itself, corresponding temperature-dependent
      measurements allow for the quantitative determination of the energetics and
      kinetics of the underlying molecular surface processes. Herein, we review recent
      advances in the STM investigation of the dynamic behaviour of adsorbed porphyrins
      at and close to room temperature. Three different case studies are discussed,
      providing insight into the dynamics of diffusion, rotation, reaction, and
      molecular switching at surfaces, based on isothermal STM measurements. The
      reviewed examples demonstrate that variable temperature STM can be a suitable
      tool to directly monitor the dynamic behaviour of individual adsorbed molecules,
      at and close to room temperature. Free base porphyrins on Cu(111) proved to be
      particularly suitable for these studies due to the strong bonding interaction
      between the iminic nitrogen atoms in the porphyrin macrocycle and the Cu
      substrate atoms. As a consequence, the corresponding activation energies for
      surface diffusion, self-metalation reaction and conformational switching are of a
      magnitude that allows for monitoring the processes at and around room
      temperature, in contrast to most previous studies, which were performed at
      cryogenic temperatures. The kinetic analysis of the surface diffusion and self
      metalation was performed using an Arrhenius approach, yielding the corresponding
      activation energies and preexponential factors. In contrast, the conformational
      switching process was analysed in the framework of transition state theory, based
      on the Eyring equation. This approach provides a more detailed insight into
      interpretable thermodynamic potentials, i.e., the enthalpic and entropic
      contributions to the activation barrier. The analysis shows that at room
      temperature the adsorption and switching behaviour of the investigated free base
      porphyrin on Cu(111) is dominated by entropic effects. Since the entropic energy
      contribution vanishes at low temperatures, the importance of experiments
      conducted at temperatures close to room temperature is emphasized. 

PMID- 24867779
TI  - Extracorporeal photopheresis in steroid-refractory acute or chronic graft-versus
      host disease: results of a systematic review of prospective studies.
AB  - Acute and chronic graft-versus-host disease (GVHD) remain major obstacles for
      successful allogeneic hematopoietic cell transplantation. Extracorporeal
      photopheresis (ECP) modulates immune cells, such as alloreactive T cells and
      dendritic cells, and improves GVHD target organ function(s) in steroid-refractory
      GVHD patients. We performed a systematic review to evaluate the totality of
      evidence regarding the efficacy of ECP for treatment of acute and chronic steroid
      refractory or steroid-dependent GVHD. Nine studies, including 1 randomized
      controlled trial, met inclusion criteria, with a total of 323 subjects. In pooled
      analyses, overall response rates (ORR) were .69 (95% confidence interval [CI],
      .34 to .95) and .64 (95% CI, .47 to .79) for acute and chronic GVHD,
      respectively. In acute GVHD organ-specific responses, ECP resulted in the highest
      ORR for cutaneous, with .84 (95% CI, .75 to .92), followed by gastrointestinal
      with .65 (95% CI, .52 to .78). Similar response rates were seen in chronic GVHD
      involving the skin and gastrointestinal tract. Conversely, ORR for chronic GVHD
      involving the lungs was only .15 (95% CI, 0 to .5). In chronic GVHD, grades 3 to
      4 adverse events were reported at .38 (95% CI, .06 to .78). ECP-related mortality
      rates were extremely low. Rates of immunosuppression discontinuation were .55
      (95% CI, .40 to .70) and .23 (95% CI, .07 to .44) for acute and chronic GVHD,
      respectively. In summary, albeit limited by numbers of available studies, pooled
      analyses of prospective studies demonstrate encouraging responses after ECP
      treatment in acute and chronic GVHD after failing corticosteroids. Further
      research efforts are needed to improve organ-specific responses.

PMID- 24867781
TI  - Effects of fat accumulation in the liver on hemodynamic variables assessed by
      Doppler ultrasonography.
AB  - PURPOSE: To investigate the effect of various degrees of fatty liver infiltration
      on hepatic hemodynamics using Doppler ultrasonography. METHODS: We included 40
      patients with hepatic steatosis and 20 healthy volunteers. Hepatic steatosis was
      quantified by a chemical shift MRI. Hepatic artery peak systolic and end
      diastolic velocity, resistance index (RI) and pulsatility index (PI), hepatic
      vein RI and PI, portal vein RI, PI, congestion index, and peak maximum velocity
      were evaluated by Doppler ultrasonography. The hepatic vein waveforms were
      classified as triphasic, biphasic, or monophasic. Kruskal-Wallis test was
      performed for comparing more than two groups. If significant differences were
      found, Mann-Whitney U test with Bonferroni correction was performed for pair-wise
      comparisons. Pearson &gch;(2) and Fisher's exact tests were used to compare
      categorical variables. RESULTS: According to MRI, 15 patients had mild, 14
      patients had moderate, and 11 patients had severe fatty infiltration. Portal vein
      peak maximum velocity was median: 19.8 (range 12-33.3), 21.1 (8-41.8), 16.6 (10.6
      24.9), and 29.2 (14.1-40.4) cm/s. Congestion index was 0.05 (0.02-0.16), 0.07
      (0.01-0.17), 0.11 (0.06-0.24), and 0.05 (0.02-0.16). Hepatic artery RI was 0.75
      (0.56-1.00), 0.66 (0.52-0.87), 0.83 (0.38-1.00), and 0.76 (0.48-2.76), and PI was
      1.83 (0.90-3.13), 1.38 (1.04-2.63), 1.97 (0.86-2.90), and 1.82 (0.70-2.90) (p =
      .046 and p = .036) in the mild, moderate, severe steatosis, and control groups,
      respectively. The rate of triphasic hepatic vein waveforms was higher in controls
      than in patients with severe steatosis. CONCLUSIONS: Portal vein flow velocity
      decreases in severe hepatic steatosis when compared with controls.

PMID- 24867783
TI  - A "light-up" and "spectrum-shift" response of aptamer-functionalized silver
      nanoclusters for intracellular mRNA imaging.
AB  - We have designed a novel multifunctional DNA scaffold for the synthesis of
      fluorescent silver nanoclusters (Ag NCs) using a one-pot approach. The obtained
      DNA/Ag NCs presented a "light-up" and "spectrum-shift" response to target DNA in
      vitro and could further image the tumor-related mRNA in living cells. 

PMID- 24867782
TI  - Irinotecan and temozolomide brain distribution: a focus on ABCB1.
AB  - Glioblastoma (GBM), the most common primary brain tumor in adults, is usually
      rapidly fatal with median survival duration of only 15 months and a 3-year
      survival rate of <7 %. Temozolomide (TMZ) is the only anticancer drug that has
      improved survival in GBM when administered with concomitant radiotherapy.
      Irinotecan (CPT-11) has also shown efficacy in recurrent gliomas monotherapy with
      moderate response. As the efficacy of GBM treatments relies on their brain
      distribution through the blood-brain barrier (BBB), the aim of the present work
      was to study, on an in vivo model, the brain distribution of TMZ, CPT-11 and its
      active metabolite, SN-38. We have focussed on the role of ABCB1, the main efflux
      transporter at the BBB level, through pharmacokinetics studies in CF1 mdr1a(+/+)
      and mdr1a(-/-) mice. Our results show that TMZ, CPT-11 and SN-38 are transported
      by ABCB1 at the BBB level with brain/plasma ratios of 1.1, 2.1 and 2.3,
      respectively.

PMID- 24867784
TI  - Reflexive culture in adolescents and adults with group A streptococcal
      pharyngitis.
AB  - BACKGROUND: Guidelines currently provide conflicting recommendations regarding
      the diagnosis of group A streptococcal (GAS) pharyngitis in adults. Clinical
      guidelines state that negative rapid antigen detection tests (RADTs) do not
      require confirmation by a backup method in adults, whereas laboratory-based
      guidelines mandate confirmation of a negative RADT in patients of all ages. The
      objective of this study was to assess the utility of reflexive culture following
      a negative RADT in adolescents and adults with suspected GAS pharyngitis.
      METHODS: A retrospective analysis of 726 patients, aged >=13 years, with negative
      RADTs and positive GAS throat cultures, was performed between 1 January 2000 and
      31 December 2011 at 2 academic medical centers in Seattle, Washington.
      Complication rates, treatment, modified Centor score, and bacterial burden in
      patients with negative RADTs and positive GAS throat cultures were assessed.
      RESULTS: Modified Centor scores >=2 were observed in 55% of patients with a
      negative RADT and positive GAS culture. Of these, 77% of patients had a moderate
      or heavy bacterial burden (>=2+). RADTs failed to detect some patients who
      presented with serious complications of GAS pharyngitis: 29 (4.0%) had
      peritonsillar abscesses and 2 (0.28%) were diagnosed with acute rheumatic fever.
      Providers found culture results to be useful for initiating antibiotic therapy or
      confirming a clinical diagnosis. Antibiotic treatment was prescribed in 68.7% of
      patients, with culture-directed initiation of therapy documented in 43.5%.
      CONCLUSIONS: Reflexive GAS culture is clinically useful when RADTs are negative.
      RADTs fail to detect a substantial number of adult patients with clinically
      significant pharyngitis who can benefit from treatment.

PMID- 24867785
TI  - Reply to Rhodes et al.

PMID- 24867786
TI  - Seroprevalence to avian influenza A(H7N9) virus among poultry workers and the
      general population in southern China: a longitudinal study.
AB  - BACKGROUND: Confirmed cases of avian influenza A(H7N9) virus infection in humans
      continue to occur in mainland China. Few confirmed cases have occurred in poultry
      workers despite potentially higher rates of exposure. METHODS: A serological
      survey was conducted in May and December 2013 in poultry market workers, and in
      March and September 2013 in the general population. Blood samples were collected
      and tested for antibodies to H7N9 and H5N1 viruses by hemagglutination inhibition
      (HI) assays. Multivariable analysis was employed to identify risk factors related
      to H7N9 infection indicated by serology among poultry workers. RESULTS: In the
      poultry workers, 36 of 501 (7.2%) in May and 56 of 375 (14.9%) in December had HI
      antibody titers >=1:160 to H7N9. Of 96 individuals who participated in both
      surveys, 52 (54.2%) workers had a >=4-fold rise in H7N9 antibody titers from May
      to December. In a multivariable analysis, female sex (odds ratio [OR], 2.713; 95%
      confidence interval [CI], 1.098-6.705) and >=10 years of occupational exposure
      (OR, 3.592; 95% CI, 1.246-10.354) were identified as risk factors for infection.
      Seroprevalence against H5N1 at >=1:160 was low in May (4/501 [0.8%]) and December
      (3/375 [0.8%]). In the general population, 0 of 417 individuals in March and 0 of
      408 individuals in September had antibody titers >=1:160 to H7N9 or to H5N1.
      CONCLUSIONS: Although none of the participants in our study had virologically
      confirmed H7N9 infection, the high proportion of poultry workers with serologic
      evidence of H7N9 infection between May and December 2013 suggests a substantial
      risk of mild H7N9 infections in this group, supporting stricter control measures
      in live poultry markets.

PMID- 24867787
TI  - HIV and hepatitis C virus infection in the United States: whom and how to test.
AB  - In the United States, of the 1.1 million persons infected with human
      immunodeficiency virus (HIV) and the 2.7 million infected with hepatitis C virus
      (HCV), approximately 16% and 50%, respectively, are unaware of their infection.
      Highly effective treatments have turned both diseases into manageable conditions,
      and in the case of hepatitis C, a disease that can be cured. Early diagnosis is
      imperative so that infected persons can take measures to stay healthy, get into
      care, benefit from therapy, and reduce the risk of transmission. In this report,
      we review current recommendations provided by the Centers for Disease Control and
      Prevention (CDC) and the United States Preventive Services Task Force on whom to
      screen for HIV and HCV infections, and recommendations from the CDC, the
      Association of Public Health Laboratories, and the Clinical and Laboratory
      Standards Institute on how to test for these infections. 

PMID- 24867788
TI  - Impact of loading doses on the time to adequate predicted beta-lactam
      concentrations in prolonged and continuous infusion dosing schemes.

PMID- 24867790
TI  - Editorial commentary: molecular diagnosis of child pneumonia: high yield,
      uncertain specificity.

PMID- 24867791
TI  - Vancomycin exposure in patients with methicillin-resistant Staphylococcus aureus
      bloodstream infections: how much is enough?
AB  - BACKGROUND: Contemporary vancomycin dosing schemes are designed to achieve an
      area under the curve (AUC) to minimum inhibitory concentration (MIC) ratio of
      >=400. However, scant clinical data exist to support this target and available
      data relied on pharmacokinetic formulas based on daily vancomycin dose and
      estimated renal function (demographic pharmacokinetic model) to estimate AUCs.
      METHODS: A cohort study of hospitalized, adult, nondialysis patients with
      methicillin-resistant Staphylococcus aureus bloodstream infections treated with
      vancomycin was performed to quantitatively evaluate the relationship between
      vancomycin exposure and outcomes. Bayesian techniques were used to estimate
      vancomycin exposure profile for day 1 and 2 of therapy for each patient based on
      their dosing schedule and collected concentrations. Classification and Regression
      Tree (CART) analysis was used to identify day 1 and 2 exposure thresholds
      associated with an increased risk of failure. Failure was defined as 30-day
      mortality, bacteremia was >=7 days, or recurrence. RESULTS: During the study
      period, 123 cases met criteria. Failure was uniformly less pronounced
      (approximately 20% less in absolute value) in patients who achieved the CART
      derived day 1 and 2 thresholds for AUC/MIC by broth microdilution and AUC/MIC by
      Etest. In the multivariate analyses, all risk ratios were approximately 0.5 for
      all CART-derived AUC/MIC exposure thresholds, indicating that achievement of CART
      derived AUC/MIC exposure thresholds was associated with a 2-fold decrease in
      failure. CONCLUSIONS: These findings establish the critical importance of daily
      AUC/MIC ratios during the first 2 days of therapy. As with all observational
      studies, these findings should be interpreted cautiously and validated in a
      multicenter randomized trial before adoption into practice.

PMID- 24867789
TI  - Etiology of severe childhood pneumonia in the Gambia, West Africa, determined by
      conventional and molecular microbiological analyses of lung and pleural aspirate
      samples.
AB  - Molecular analyses of lung aspirates from Gambian children with severe pneumonia
      detected pathogens more frequently than did culture and showed a predominance of
      bacteria, principally Streptococcus pneumoniae, >75% being of serotypes covered
      by current pneumococcal conjugate vaccines. Multiple pathogens were detected
      frequently, notably Haemophilus influenzae (mostly nontypeable) together with S.
      pneumoniae. 

PMID- 24867792
TI  - Antimicrobial resistance and susceptibility testing of anaerobic bacteria.
AB  - Infections due to anaerobic bacteria can be severe and life-threatening.
      Susceptibility testing of anaerobes is not frequently performed in laboratories,
      but such testing is important to direct appropriate therapy. Anaerobic resistance
      is increasing globally, and resistance trends vary by geographic region. An
      overview of a variety of susceptibility testing methods for anaerobes is
      provided, and the advantages and disadvantages of each method are reviewed.
      Specific clinical situations warranting anaerobic susceptibility testing are
      discussed. 

PMID- 24867793
TI  - Protective effects of hesperidin on concanavalin A-induced hepatic injury in
      mice.
AB  - Hesperidin (HDN) is a citrus bioflavonoid, which widely exists in many plants.
      Previous researches have proved that HDN has several functions such as anti
      oxidant, anti-tumor, anti-inflammatory, immune regulation and so on. In the
      present study, we explored the protective effects of HDN on concanavalin A (Con
      A)-induced hepatic injury. Acute hepatic injury model was established
      successfully by intravenous administration of Con A (15 mg/kg) in male C57BL/6
      mice, and HDN was pretreated for 10 days before Con A challenge. It was found
      that the hepatic injury was notably improved in HDN pretreated mice. Furthermore,
      hepatic oxidative stress and the production of proinflammatory cytokines
      including TNF-alpha and IFN-gamma were decreased by HDN pretreatment. More
      importantly, compared with Con A-treated mice, the expression and releasing of
      HMGB1 and T-cell activation were markedly reduced in HDN pretreated mice. Thus,
      these results suggest that HDN protects mice from Con A-induced hepatic injury by
      suppressing hepatocyte oxidative stress, producing cytokines, expressing and
      releasing HMGB1 and activating T cells.

PMID- 24867794
TI  - Inhibiting effect of Radix Hedysari Polysaccharide (HPS) on endotoxin-induced
      uveitis in rats.
AB  - PURPOSE: The aim of this study is to investigate the anti-inflammatory effect of
      Radix Hedysari Polysaccharide (HPS) on clinical indicators, the expression of
      Toll-like receptor-4 (TLR4) and its downstream transduction molecules during
      endotoxin-induced uveitis in rats. METHODS: EIU was induced through the
      intraperitoneal injection of male Wistar rats with lipopolysaccharide (LPS 200
      MUg). HPS (400mg/kg), DXM (1mg/kg) or an equivalent volume of normal saline was
      injected intraperitoneally 1h before the LPS induction. The clinical
      manifestation was observed and scored at 2-h intervals using a slit microscope.
      The degree of inflammatory reaction was determined by routine histological
      examinations, and the expression of TLR4 and MyD88 in the iris-ciliary body
      complex was detected through a double-labeled immunofluorescence study. Real-time
      RT-PCR was used to assess the effects of HPS on the expression of the TLR4
      complex, MyD88 and NF-kappaB p65 mRNA. The protein expression levels of TLR4,
      MyD88 and NF-kappaB p65 were examined by western blot. RESULTS: HPS treatment
      produced similar therapeutic results with dexamethasone by significantly reducing
      the clinical severity of EIU as well as fibrin exudations and inflammatory cell
      infiltration in the eye. Correspondingly, according to the immunofluorescence
      results, HPS treatment significantly suppressed the expression of TLR4 and MyD88
      in the iris-ciliary body complex. HPS treatment could also remarkably reduce the
      mRNA and protein expression of the TLR4 complex, MyD88 and NF-kappaB p65.
      CONCLUSION: HPS can suppress the intraocular inflammation observed in EIU by
      inhibiting TLR4 and its downstream signal transduction pathway.

PMID- 24867795
TI  - Polysaccharides from Inonotus obliquus sclerotia and cultured mycelia stimulate
      cytokine production of human peripheral blood mononuclear cells in vitro and
      their chemical characterization.
AB  - Inonotus obliquus is an edible and medicinal mushroom to treat many diseases. In
      the present study, polysaccharides and fractions were isolated and purified by
      DEAE-52 and Sephadex G-200 chromatography from I. obliquus wild sclerotia,
      culture broth and cultured mycelia under submerged fermentation. The extracts and
      fractions could significantly induce the secretion of TNF-alpha, IFN-gamma, IL
      1beta, and IL-2 in human peripheral blood mononuclear cells (PBMCs) and showed no
      toxicity to PBMCs. The stimulation effect of the six extracts and eight fractions
      on the four-cytokine production was dose-dependent. Sclerotial polysaccharides
      were more effective in the four-cytokine production at 150 MUg/ml while
      exopolysaccharides and endopolysacchrides showed a much better effect on IL-1beta
      production at 30 MUg/ml. Purified fractions from exopolysaccharides and
      endopolysaccharides were more effective than the fraction from sclerotia in most
      cytokine production. These heteropolysaccharide-protein conjugates mainly
      contained glucose, galactose, and mannose. Protein content, molecular weight,
      monosaccharide molar ratio, and anomeric carbon configuration differed from each
      other and had effects on the cytokine induction activity of the polysaccharides
      to some extent.

PMID- 24867796
TI  - The relationship between the g.27450A>T genetic variant of OPG gene and
      osteoporosis in Chinese postmenopausal women.
AB  - The objective of this study is to evaluate the relationship between the
      g.27450A>T genetic variant of osteoprotegerin (OPG) gene and osteoporosis in
      Chinese postmenopausal women. A total of 886 subjects were enrolled in this
      study. The femoral neck hip, lumbar spine (L2-4), and total hip bone mineral
      density (BMD) were detected by dual-energy X-ray absorptiometry (DEXA). The
      genotyping of the g.27450A>T genetic variant of OPG gene was investigated by
      polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and
      DNA sequencing methods. Significant differences in the femoral neck hip, lumbar
      spine (L2-4), and total hip BMD among different genotypes were found, and the
      subjects with AA genotype were significantly higher than those of AT and TT
      genotypes (P<0.05). The allele-A could be a decreased risk factor for
      osteoporosis. Results from this study support that the g.27450A>T genetic variant
      of OPG gene has potential relationship with BMD and osteoporosis in Chinese
      postmenopausal women. 

PMID- 24867797
TI  - Tumor necrosis factor-alpha modulates epithelial mesenchymal transition mediators
      ZEB2 and S100A4 to promote cholangiocarcinoma progression.
AB  - BACKGROUND: The epithelial-mesenchymal transition (EMT) process strongly
      contributes to cancer metastasis. This study was to investigate the alteration of
      EMT-related proteins (ZEB1, ZEB2 and S100A4) in cholangiocarcinoma (CCA) tissues.
      The effect of tumor necrosis factor-alpha (TNF-alpha) on the expression of those
      molecules in CCA cells was investigated. METHODS: The quantitative reverse
      transcription-polymerase chain reaction (qRT-PCR) assay was used to quantify
      ZEB1, ZEB2 and S100A4 mRNA levels in 50 CCA tissues and related its expression to
      clinicopathological data. ZEB2 protein immunostaining was investigated in 165 CCA
      tissues. The effect of TNF-alpha on EMT-related CCA cell migration was evaluated
      using qRT-PCR, immunofluorescence and transwell migration assays. RESULTS: ZEB2
      and S100A4 mRNA levels were found to be higher in CCA tissues. High levels of
      S100A4 mRNA and ZEB2 protein were significantly associated with CCA metastasis (P
      = 0.04 and P = 0.03). Moreover, a trend toward statistical association was found
      with high levels of both ZEB2 mRNA and protein with shorter survival time (P =
      0.10 and P = 0.19). In addition, TNF-alpha induced CCA cell migration by the
      induction of transforming growth factor-beta (TGF-beta) resulting in ZEB2 and
      S100A4 mRNA and protein activation. CONCLUSIONS: These studies demonstrate that
      TNF-alpha plays crucial role in the progression of CCA by activating TGF-beta
      signaling and the induction of ZEB2 and S100A4, EMT-related proteins expression.

PMID- 24867798
TI  - [Gait disorders in the elderly].
AB  - Gait disorders are one of the most common gerontoneurological symptoms. Falls
      that occasionally cause severe injuries are highly relevant consequences. A
      clinical neurological examination and inspectoral gait analysis are the core
      investigations of the diagnostic process, which yields hypotheses with respect to
      the impaired structures as well as to specific diagnostic measures. The
      supplemental motor assessment quantifies the resulting impairment of mobility and
      risk of falling with the help of well-established instruments. Characteristic of
      gait disorders in the elderly are the multifactorial causes which make the
      complete identification, correct prioritization and adequate treatment the
      biggest challenges. The therapeutic concept is multiprofessional and includes the
      causal treatment of underlying diseases, physiotherapeutic training programs,
      prescription of medical aids and nutritional interventions. Identification and
      modification of risk factors (including those that are iatrogenic) are of
      superior importance.

PMID- 24867799
TI  - Sodium taurocholate cotransporting polypeptide (SLC10A1) deficiency: conjugated
      hypercholanemia without a clear clinical phenotype.
AB  - The enterohepatic circulation of bile salts is an important physiological route
      to recycle bile salts and ensure intestinal absorption of dietary lipids. The
      Na(+)-taurocholate cotransporting polypeptide SLC10A1 (NTCP) plays a key role in
      this process as the major transporter of conjugated bile salts from the plasma
      compartment into the hepatocyte. Here we present the first patient with NTCP
      deficiency, who was clinically characterized by mild hypotonia, growth
      retardation, and delayed motor milestones. Total bile salts in plasma were
      extremely elevated (up to 1,500 MUM, ref. <16.3) but there were no clinical signs
      of cholestatic jaundice, pruritis, or liver dysfunction. Bile salt synthesis and
      intestinal bile salt signaling were not affected, as evidenced by normal plasma
      7alpha-hydroxy-4-cholesten-3-one (C4) and FGF19 levels. Importantly, the presence
      of secondary bile salts in the circulation suggested residual enterohepatic
      cycling of bile salts. Sequencing of the SLC10A1 gene revealed a single
      homozygous nonsynonymous point mutation in the coding sequence of the gene,
      resulting in an arginine to histidine substitution at position 252. Functional
      studies showed that this mutation resulted in a markedly reduced uptake activity
      of taurocholic acid. Immunofluorescence studies and surface biotinylation
      experiments demonstrated that the mutant protein is virtually absent from the
      plasma membrane. CONCLUSION: We describe the identification of NTCP deficiency as
      a new inborn error of metabolism with a relatively mild clinical phenotype. The
      identification of NTCP deficiency confirms that this transporter is the main
      import system for conjugated bile salts into the liver but also indicates that
      auxiliary transporters are able to sustain the enterohepatic cycle in its
      absence.

PMID- 24867800
TI  - Quadriparesis from air emboli during percutaneous nephrolithotomy.
AB  - Quadriparesis is a potentially catastrophic complication during operative
      procedures. It may result from a number of different types of central nervous
      system insults. A case of quadriparesis following an otherwise unremarkable
      percutaneous nephrolithotomy surgery is reported. The quadriparesis resulted from
      multiple air micro emboli. 

PMID- 24867804
TI  - Neural correlates of risky decision making in anxious youth and healthy controls.
AB  - BACKGROUND: Pediatric anxiety disorders are chronic and impairing conditions that
      are characterized by risk aversion and avoidance; however, the neural correlates
      of decision making under risk in anxious youth remain poorly understood. METHODS:
      Youth with a primary diagnosis of separation anxiety, social phobia, or
      generalized anxiety disorder (n = 16) and healthy controls (n = 15), performed a
      risky decision-making task under conditions of potential gain or loss while
      undergoing a functional magnetic resonance imaging (fMRI) scan. RESULTS: Analyses
      were conducted to examine neural response to risky versus nonrisky choices in
      each condition. Anxious youth made fewer risky choices during potential loss
      compared to controls. Both groups elicited strong frontostriatal activation
      during risky choice. During risky choice in the gain condition, controls
      exhibited greater activation in ventral putamen during risky choice than during
      nonrisky choice and than anxious youth. In the loss condition, controls exhibited
      greater activation in medial prefrontal cortex during risk-taking while anxious
      youth exhibited greater engagement of amygdala and insula. Neural activation
      during risky choice was associated with individual differences in anxiety symptom
      severity, such that as anxiety symptomatology increased, there was decreased
      recruitment of the ventral striatum in the gain condition and increasing
      recruitment of the amygdala in the loss condition. CONCLUSIONS: Youth with
      anxiety disorders differ from their nonanxious peers on both behavioral and
      neurobiological indices during risky decision making; these differences are
      exacerbated by symptom severity and they shed light on the pathophysiology of
      pediatric anxiety. Neural correlates of risky decision making in anxious youth
      and healthy controls.

PMID- 24867803
TI  - Leptomeningeal metastasis: a Response Assessment in Neuro-Oncology critical
      review of endpoints and response criteria of published randomized clinical
      trials.
AB  - PURPOSE: To date, response criteria and optimal methods for assessment of outcome
      have not been standardized in patients with leptomeningeal metastasis (LM).
      METHODS: A Response Assessment in Neuro-Oncology working group of experts in LM
      critically reviewed published literature regarding randomized clinical trials
      (RCTs) and trial design in patients with LM. RESULTS: A literature review
      determined that 6 RCTs regarding the treatment of LM have been published, all of
      which assessed the response to intra-CSF based chemotherapy. Amongst these RCTs,
      only a single trial attempted to determine whether intra-CSF chemotherapy was of
      benefit compared with systemic therapy. Otherwise, this pragmatic question has
      not been formally addressed in patients with solid cancers and LM. The
      methodology of the 6 RCTs varied widely with respect to pretreatment evaluation,
      type of treatment, and response to treatment. Additionally there was little
      uniformity in reporting of treatment-related toxicity. One RCT suggests no
      advantage of combined versus single-agent intra-CSF chemotherapy in patients with
      LM. No specific intra-CSF regimen has shown superior efficacy in the treatment of
      LM, with the exception of liposomal cytarabine in patients with lymphomatous
      meningitis. Problematic with all RCTs is the lack of standardization with respect
      to response criteria. There was considerable variation in definitions of response
      by clinical examination, neuroimaging, and CSF analysis. CONCLUSION: Based upon a
      review of published RCTs in LM, there exists a significant unmet need for
      guidelines for evaluating patients with LM in clinical practice as well as for
      response assessment in clinical trials.

PMID- 24867807
TI  - Vigna unguiculata is nodulated in Spain by endosymbionts of Genisteae legumes and
      by a new symbiovar (vignae) of the genus Bradyrhizobium.
AB  - Vigna unguiculata was introduced into Europe from its distribution centre in
      Africa, and it is currently being cultivated in Mediterranean regions with
      adequate edapho-climatic conditions where the slow growing rhizobia nodulating
      this legume have not yet been studied. Previous studies based on rrs gene and ITS
      region analyses have shown that Bradyrhizobium yuanmingense and B. elkanii
      nodulated V. unguiculata in Africa, but these two species were not found in this
      study. Using the same phylogenetic markers it was shown that V. unguiculata, a
      legume from the tribe Phaseolae, was nodulated in Spain by two species of group
      I, B. cytisi and B. canariense, which are common endosymbionts of Genisteae in
      both Europe and Africa. These species have not been found to date in V.
      unguiculata nodules in its African distribution centres. All strains from
      Bradyrhizobium group I isolated in Spain belonged to the symbiovar genistearum,
      which is found at present only in Genisteae legumes in both Africa and Europe. V.
      unguiculata was also nodulated in Spain by a strain from Bradyrhizobium group II
      that belonged to a novel symbiovar (vignae). Some African V. unguiculata
      nodulating strains also belonged to this proposed new symbiovar. 

PMID- 24867810
TI  - Isocitrate dehydrogenase mutations in chondrosarcoma: the crossroads between
      cellular metabolism and oncogenesis.
AB  - PURPOSE OF REVIEW: This article reviews the most recent developments and
      implications in regard to isocitrate dehydrogenase mutations in chondrosarcoma, a
      disease in which currently available systemic therapies have proven
      inefficacious, with an emphasis on how disruption in normal cellular metabolism
      plays a role in oncogenesis. RECENT FINDINGS: The development of acquired
      isocitrate dehydrogenase-1/isocitrate dehydrogenase-2 mutations has been
      described in multiple tumors and more recently in chondrosarcomas. The impact of
      these mutations has been the focus of multiple research efforts during the last
      years, allowing us to better understand the impact of the mutation, including its
      interaction with other proteins, changes in expression of genes involved in tumor
      genesis, the oncogenic potential of 2-hydroxyglutarate, the impact on cellular
      proliferation and differentiation, and the influence on the epigenetic state of
      cells owing to changes in DNA and histone methylation patterns. New compounds
      targeting the mutation have been developed. SUMMARY: This mutation is the first
      of its kind described in chondrosarcoma, serving as an identifying marker of
      chondroid differentiation, and becoming the first molecular target with potential
      anticancer effect, translating into the development of therapies targeting these
      mutations currently being tested further in preclinical models and clinical
      trials.

PMID- 24867808
TI  - Chryseobacterium oleae sp. nov., an efficient plant growth promoting bacterium in
      the rooting induction of olive tree (Olea europaea L.) cuttings and emended
      descriptions of the genus Chryseobacterium, C. daecheongense, C. gambrini, C.
      gleum, C. joostei, C. jejuense, C. luteum, C. shigense, C. taiwanense, C.
      ureilyticum and C. vrystaatense.
AB  - A novel non-motile, Gram-staining-negative, yellow-pigmented bacterium,
      designated CT348(T), isolated from the ectorhizosphere of an organic olive tree
      in Spain and characterised as an efficient plant growth promoting bacterium, was
      investigated to determine its taxonomic status. The isolate grew best in a
      temperature range of 5-35 degrees C, at pH 5.0-8.0 and with 0-1% (w/v) NaCl.
      Chemotaxonomic and molecular characteristics of the isolate matched those
      described for members of the genus Chryseobacterium. The DNA G+C content of the
      novel strain was 38.2mol%. The strain contained a polyamine pattern with sym
      homospermidine as the major compound and produced flexirubin-type pigments. MK-6
      was the dominant menaquinone and the major cellular fatty acids were iso-C15:0,
      C17:1omega9c, iso-C17:0 3-OH and iso-C15:0 2-OH. The main polar lipids were
      phosphatidylethanolamine and several unidentified lipids and aminolipids. The 16S
      rRNA gene showed 92.2-97.8% sequence identity with the members of the genus
      Chyseobacterium. Based on the phenotypic traits and DNA-DNA hybridizations with
      the type strains of the most closely related species, the isolate is shown to
      represent a novel species, Chyseobacterium oleae, type strain CT348(T) (=DSM
      25575 =CCUG 63020). Emended descriptions of the genus Chryseobacterium and C.
      daecheongense, C. gambrini, C. gleum, C. joostei, C. jejuense, C. luteum, C.
      shigense, C. taiwanense, C. ureilyticum and C. vrystaatense are also proposed.

PMID- 24867811
TI  - Synthesis and characterization of combined cross-linked laccase and tyrosinase
      aggregates transforming acetaminophen as a model phenolic compound in
      wastewaters.
AB  - Laccase (EC 1.10.3.2) and tyrosinases (EC 1.14.18.1) are ubiquitous enzymes
      present in nature as they are known to originate from bacteria, fungi, plants,
      etc. Both laccase and tyrosinase are copper-containing phenoloxidases requiring
      readily available O2 without auxiliary cofactor for their catalytic
      transformation of numerous phenolic substrates. In the present study, laccase and
      tyrosinase have been insolubilized as combined crosslinked enzyme aggregates
      (combi-CLEA) using chitosan, a renewable and biodegradable polymer, as
      crosslinker. The combi-CLEA, with specific activity of 12.3 U/g for laccase and
      167.4 U/g for tyrosinase, exhibited high enzymatic activity at pH5-8 and
      temperature at 5-30 degrees C, significant resistance to denaturation and no
      diffusional restriction to its active site based upon the Michaelis-Menten
      kinetic parameters. Subsequently, the combi-CLEA was applied to the
      transformation of acetaminophen as a model phenolic compound in samples of real
      wastewaters in order to evaluate the potential efficiency of the biocatalyst. In
      batch mode the combi-CLEA transformed more than 80% to nearly 100% of
      acetaminophen from the municipal wastewater and more than 90% from the hospital
      wastewater. UPLC-MS analysis of acetaminophen metabolites showed the formation of
      its oligomers as dimers, trimers and tetramers due to the laccase and 3
      hydroxyacetaminophen due to the tyrosinase.

PMID- 24867812
TI  - Anticoagulation of cardiomyopathy in children.
AB  - OBJECTIVES: Cardiomyopathy is a common cause of heart failure in children.
      Thrombosis is a potential significant secondary complication. Thus warfarin is
      recommended by the American College of Chest Physicians for the treatment of
      children with cardiomyopathy despite the lack of published evidence to support
      its use. METHODS: A retrospective clinical audit to estimate the rates of major
      bleeding and incidence of thromboembolism associated with oral anticoagulant
      therapy (warfarin) for primary thromboprophylaxis in a cohort of children with
      cardiomyopathy. Relevant outcomes including thrombosis and major haemorrhage were
      defined a priori according to internationally accepted definitions. RESULTS: 36
      children (35.9 warfarin years) were examined, with 25% taking warfarin for
      greater than 1year. Primary reasons for discontinuation of warfarin therapy were
      cardiac transplantation (n=7), transition to VAD (n=1), improved cardiac function
      (n=17), transfer of care (n=3), change to aspirin (n=2). The mean age at starting
      warfarin was 5.4years (range 0.2-15.2). The most common Target Therapeutic Range
      (TTR) for warfarin therapy was 2.0 - 3.0. TTR achievement was normally
      distributed and occurred in a mean 48.5% of all INR tests. There were zero
      warfarin related adverse events, including thrombosis or haemorrhage. CONCLUSION:
      The low rate of TTR achievement is consistent with previously reported TTR
      achievement rates for infants. In addition the low rate of TTR achievement was
      likely influenced by the clinical profile of this complicated condition in
      children. Nonetheless, this data shows that the clinical outcomes for this cohort
      are acceptable and warfarin therapy can be safe in children with cardiomyopathy.

PMID- 24867814
TI  - The prion hypothesis of Parkinson's disease: this hot topic just got hotter.

PMID- 24867815
TI  - Antibody and cytokine responses to Giardia excretory/secretory proteins in
      Giardia intestinalis-infected BALB/c mice.
AB  - The humoral and cellular responses against excretory/secretory proteins and
      soluble extracts of Giardia intestinalis were evaluated in the course of
      experimental G. intestinalis infection in BALB/c mice. Production of IgG1, IgG2a,
      IgA, and IgE antibodies against excreted/secreted proteins and soluble extract
      was detected after infection by G. intestinalis. Specific IgA antibody against
      E/S proteins and soluble extract form intestinal fluids in infected mice was
      detected by ELISA. The Western blotting identified proteins of 30, 58, 63, and 83
      kDa for IgA and IgG, respectively. High proliferation rate in vitro of spleen
      cell and secretion of interleukin-4 (IL-4) at 21 days p.i. after stimulation with
      excreted/secreted proteins and low proliferative response in the presence of
      soluble extract in infected BALB/c mice was observed. High production of
      interferon gamma (IFN-gamma) and interleukin-5 (IL-5) at the time of decreasing
      cyst output (14-21 days p.i.) in infected mice was recorded, suggesting the
      important role of these cytokines in the control of the infection. Interestingly,
      progressive and gradual increase of the interleukin-10 after stimulation with
      both preparations was recorded from 7 days until 28 days after infection,
      indicating the possible regulatory effect of these antigens on the immune
      response during Giardia infection. Therefore, the infection by Giardia duodenalis
      stimulates a mixed response Th1 and Th2, mainly stimulated by excretory/secretory
      antigens. The immunogenicity of these antigens may be a suitable for
      identification of the proteins related with the effective immune response in the
      course of infection by G. duodenalsis.

PMID- 24867817
TI  - NLRP3, a potential therapeutic target for type 2 diabetes?

PMID- 24867816
TI  - The effects of anti-diabetic drugs on LDL subclasses: any role for colesevelam?

PMID- 24867813
TI  - miRNAs at the interface of cellular stress and disease.
AB  - microRNAs (miRNAs) are a family of small, non-coding RNAs, which provides broad
      silencing activity of mRNA targets in a sequence-dependent fashion. This review
      explores the hypothesis that the miRNA machinery is intimately linked with the
      cellular stress pathway and apparatus. Stress signaling potentially alters the
      function of the miRNA-bioprocessing core components and decompensates regulation.
      In addition, dysregulation of miRNA activity renders the cell more prone to
      stress and emerges as a new pathway for age-related insults and diseases, such as
      neurodegeneration. 

PMID- 24867818
TI  - Atypical penile Mondor's disease - involvement of the circumflex vein.
AB  - Mondor's disease is a rare condition characterised by superficial
      thrombophlebitis of subcutaneous veins, most commonly over the anterior chest
      wall. Penile Mondor's disease is rarer, arising out of thrombophlebitis of the
      penile veins. It typically involves the dorsal vein of the penis and presents
      with a cord-like indurated lesion with a beaded feel, palpable along the length
      of the involved vein. Though penile Mondor's disease involving the dorsal vein of
      the penis has been reported by many authors, we report a peculiar case of penile
      Mondor's disease in a 26-year-old sexually active man with thrombophlebitis of
      the circumflex vein of the penis with sparing of the dorsal vein. Diagnosis was
      confirmed on Doppler ultrasonography of the penile venous system. Despite
      exhaustive history taking, no cause could be elicited. The lesion completely
      subsided within three days with daily local hot fomentation. We propose the term
      'atypical penile Mondor's disease' for such a case. 

PMID- 24867819
TI  - Get Yourself Tested 2011-2012: findings and prevalence of Chlamydia trachomatis
      and Neisseria gonorrhoeae at an urban public health system.
AB  - During April 2011 and April 2012 the Get Yourself Tested campaign was launched
      throughout the Cook County Health and Hospitals System to promote testing of
      Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) among 15-25-year-olds
      in a high-prevalence urban community. Retrospective data were collected and
      analysed. Demographic differences by CT and GC positivity were evaluated along
      with factors associated with CT and GC status. A total of 2853 tests were
      conducted among individuals aged 15-25 years. A total of 2060 (72%) females and
      793 (28%) males were tested. Of those tested, 488 (17%) individuals tested
      positive for either CT or GC or both; 400 (14%) were positive for CT, 139 (5%)
      were positive for GC. The prevalence for GC was 8.8% (n = 70) in males compared
      to 3.3% (n = 69) in females (p < 0.001) and the prevalence of CT was 16% (n =
      127) for males compared to 13.3% (n = 273) for females (p = 0.057). Women in a
      high-risk population are more likely to get tested for sexually transmitted
      infections; however, men are more likely to test positive for CT and GC. Get
      Yourself Tested is an important campaign to encourage wider spread testing among
      populations at risk in Cook County. 

PMID- 24867821
TI  - (19)F NMR monitoring of the eukaryotic 20S proteasome chymotrypsin-like activity:
      an investigative tool for studying allosteric regulation.
AB  - The proteasome displays three distinct proteolytic activities. Currently,
      proteasome inhibitors are evaluated using specific fluorescent substrates for
      each of the individual active sites. However, the photophysical properties of the
      commonly used fluorophores are similar and thus, the simultaneous monitoring of
      the three proteolytic activities is not possible. We have developed a bimodal
      fluorescent fluorinated substrate as a novel tool to study the chymotrypsin-like
      (ChT-L) proteolytic activity and its regulation by inhibitors and by substrates
      of trypsin-like (T-L) and caspase-like sites (PA). We demonstrate that this
      substrate is reliable to evaluate the ChT-L inhibitory activity of new molecules
      either by fluorescence or (19)F NMR spectroscopy. We have found that the ChT-L
      activity is dramatically reduced in the presence of T-L and PA substrates. This
      work provides a proof of concept that the fluorinated substrate enables
      investigation of the allosteric regulation of the ChT-L activity. 

PMID- 24867820
TI  - Elevated urinary leukocyte esterase as a potential surrogate marker for HIV
      sexual transmission risks in men receiving antiretroviral therapy.
AB  - Local genital tract inflammation stimulates leukocyte activity and causes HIV
      shedding, potentially increasing HIV sexual infectiousness. Although there are
      available clinical markers for genital tract inflammation, such as urinary
      leukocyte esterase, none have yet been examined in relation to HIV sexual risk
      behaviours. We sought to examine the association between urinary leukocyte
      esterase and sexual practices. Sexually active men living with HIV and receiving
      antiretroviral therapy (ART, N = 290) provided urine specimens and completed
      behavioural health assessments. HIV RNA tests and CD4 cell counts were abstracted
      from medical records. Urine specimens were analysed for leukocyte esterase using
      a standard point-of-care dipstick test. Thirty-one (10.6%) participants tested
      positive for leukocyte esterase. Logistic regression models did not indicate
      differences between men with elevated and un-elevated leukocyte activity on
      demographic, health, recent sexually transmitted infection symptoms and diagnoses
      or substance use. However, men with elevated leukocyte activity indicated
      significantly greater sexual behaviour in the previous three months, including
      more recent unprotected sexual intercourse. A simple over-the-counter urine test
      may serve as an indicator of sexual HIV infectiousness to inform further
      evaluation and treatment of genital tract inflammation, as well as condom use
      decisions during times of increased genital tract inflammation. 

PMID- 24867823
TI  - Robust fabrication of electrospun-like polymer mats to direct cell behaviour.
AB  - Currently, cell culture systems that include nanoscale topography are widely used
      in order to provide cells additional cues closer to the in vivo environment,
      seeking to mimic the natural extracellular matrix. Electrospinning is one of the
      most common techniques to produce nanofiber mats. However, since many sensitive
      parameters play an important role in the process, a lack of reproducibility is a
      major drawback. Here we present a simple and robust methodology to prepare
      reproducible electrospun-like samples. It consists of a polydimethylsiloxane mold
      reproducing the fiber pattern to solvent-cast a polymer solution and obtain the
      final sample. To validate this methodology, poly(L-lactic) acid (PLLA) samples
      were obtained and, after characterisation, bioactivity and ability to direct cell
      response were assessed. C2C12 myoblasts developed focal adhesions on the
      electrospun-like fibers and, when cultured under myogenic differentiation
      conditions, similar differentiation levels to electrospun PLLA fibers were
      obtained. 

PMID- 24867824
TI  - Words translated in sentence contexts produce repetition priming in visual word
      comprehension and spoken word production.
AB  - Previous research with words read in context at encoding showed little if any
      long-term repetition priming. In Experiment 1, 96 Spanish-English bilinguals
      translated words in isolation or in sentence contexts at encoding. At test, they
      translated words or named pictures corresponding to words produced at encoding
      and control words not previously presented. Repetition priming was reliable in
      all conditions, but priming effects were generally smaller for contextualized
      than for isolated words. Repetition priming in picture naming indicated priming
      from production in context. A componential analysis indicated priming from
      comprehension in context, but only in the less fluent language. Experiment 2 was
      a replication of Experiment 1 with auditory presentation of the words and
      sentences to be translated. Repetition priming was reliable in all conditions,
      but priming effects were again smaller for contextualized than for isolated
      words. Priming in picture naming indicated priming from production in context,
      but the componential analysis indicated no detectable priming for auditory
      comprehension. The results of the two experiments taken together suggest that
      repetition priming reflects the long-term learning that occurs with comprehension
      and production exposures to words in the context of natural language.

PMID- 24867825
TI  - Ultra-soft cantilevers and 3-D micro-patterned substrates for contractile bundle
      tension measurement in living cells.
AB  - Actin-myosin microfilament bundles or stress-fibers are the principal tension
      generating structures in the cell. Their mechanical properties are critical for
      cell shape, motion, and interaction with other cells and extracellular matrix,
      but were so far difficult to access in a living cell. Here we propose a micro
      fabricated two-component setup for direct tension measurement on a peripheral
      bundle within an intact cell. We used 3-D substrates made of silicon elastomer to
      elevate the cell making the filament bundle at its border accessible from the
      side, and employed an ultra-soft (spring constant 0.78 nN MUm(-1)) epoxy-based
      cantilever for mechanical probing. With this setup we were able for the first
      time to measure the tension in peripheral actin bundles in living primary
      fibroblasts spread on a rigid substrate. 

PMID- 24867826
TI  - Prevention, education and information: the role of the community pharmacist in
      the management of headaches.
AB  - Headaches are among the most common disorders of the nervous system. On a global
      level, it is estimated that the prevalence of headache disorder in adults is 47
      %. A proper treatment of headaches requires training of health care personnel,
      careful diagnosis and recognition of the condition, appropriate treatment with
      cost-effective drugs, simple changements in lifestyle and patient education.
      Unfortunately, a large number of people suffering from headache disorders are not
      diagnosed and treated. The unsatisfied needs in migraine can be faced by
      involving the pharmacist in the management of the pathology. To really understand
      which are the activities and the potential of community pharmacies in the
      management of patients with headache or migraine we took into account studies
      conducted around the world during the last 5 years. Based on the data collected
      it is clear that the role of the community pharmacist may be crucial in managing
      patients with headache or migraine but only if he receives an adequate and
      continuous education both on the management of therapies and maintains a stable
      relationship with the medical doctor and/or patient. In Piedmont a specific study
      to identify migraine sufferers has involved the community pharmacies in the
      administration of a questionnaire, specially crafted by the Italian Headache
      Foundation (FICEF non-profit association).

PMID- 24867827
TI  - Migraine attacks in the pharmacy: a survey in Piedmont, Italy.
AB  - Headache patients often consult a pharmacist in an attempt to obtain momentary
      pain relief without having been given any previous expert advice. A specific
      questionnaire was distributed to the pharmacies in order to assess the patterns
      of use and dispensing of analgesic medications to the headache patient who turns
      to the pharmacist for relief of a painful attack. This study aimed at identifying
      migraine patients who self-medicated, with further end points including whether
      these patients shared any particular clinical characteristics, the most common
      type of analgesic medications used, and what, if anything, was recommended by the
      pharmacist; lastly, which health care professional, if any, routinely managed the
      patient's headaches. A total of 9,100 questionnaires were distributed to the
      pharmacies and the complete 3,065 were included in the database. The ID Migraine
      Screener Test was used to classify subjects into 4 groups: "Definite migraine"
      (3/3 positive answers: n = 1,042; 34 %), "Probable migraine" (2/3: n = 969; 31.6
      %), "Unlikely migraine" (1/3: n = 630; 20.5 %), and "Other headaches" (0/3: n =
      424; 13.8 %). Only Definite and Probable migraines (n = 2,011) are considered in
      this paper. Amongst the drugs usually taken by the patients, NSAIDs were more
      common in the Probable migraine group (60.7 %) than in the Definite migraine
      (44.7 %) group (p < 0.001). On the contrary, triptans were more commonly used by
      the Definite migraine group (42.9 %) than the Probable migraine (23.7 %) group (p
      < 0.001), and combination drugs were preferentially (p < 0.001) chosen by the
      Definite (13.8 %) rather than the Probable migraine group (8.7 %). A total of
      29.2 % of respondents reported that for the management of their headaches, they
      did not avail themselves of any type of professional healthcare, such as their
      general practitioner, a headache specialist, or a Headache Center.

PMID- 24867828
TI  - Symptomatic treatment of migraine: from scientific evidence to patient
      management.
AB  - All migraine patients need symptomatic treatment to stop individual attacks or,
      at least, significantly relieve pain. When attacks are very frequent (more than 3
      days of headache per month on average), they will also need preventive treatment.
      The first physician the patient must address to for preventive treatment is the
      general practitioner (GP). If the medication prescribed by the GP is not
      effective or there is overuse of symptomatic drugs, the patient will have to be
      referred to a neurologist or a headache clinic. The drugs to be used as
      symptomatic treatment are triptans and non-steroidal anti-inflammatory drugs.
      Combination therapy with antiemetics is also important. While specialists will
      base their therapeutic decisions on guidelines in the literature and on their
      personal experience, GPs do not yet have any easy-to-use tools to support them.
      To fill this gap, an algorithm is proposed here that can be easily used by GPs to
      make decisions during their patients' migraine attacks.

PMID- 24867829
TI  - Treatment of tension-type headache: from old myths to modern concepts.
AB  - Tension-type headache (TTH) is the second most common human disease, accounting
      for intense disability, high costs and numerous workdays lost. Tension-type
      headache is less simple and easy-to-treat than commonly thought. Antidepressants,
      despite their poor tolerability, are still the first-choice drugs for preventing
      TTH. The most widely studied non-pharmacological approach to TTH, cognitive
      behavioral techniques, effectively relieve pain only in selected patients. The
      most frequently used and recommended treatments for acute TTH, NSAIDs and
      paracetamol have scarce efficacy as documented by their low therapeutic gain over
      placebo in the 2-h pain-free response. Their effectiveness may be increased by a
      more proper use and by the adjunction of caffeine, antiemetics, myorelaxants or
      tranquillizers but the risk of medication-overuse headache must be considered.
      Hence, the need for more effective and tailored treatments in TTH remains. 

PMID- 24867830
TI  - Difficulties in work-related activities among migraineurs are scarcely collected:
      results from a literature review.
AB  - Migraine affects work productivity in terms of missed workdays and days with
      reduced productivity. In this literature review, we looked for papers addressing
      specific difficulties in work-related activities. Twenty-three papers were
      included in the review, reporting data on 51,135 patients. Results showed that
      there is some evidence for limitations in skills such as problem solving, and
      activities such as speaking and driving. However, the way in which problems with
      remunerative employment are addressed is limited to concepts such as reduced
      performance or inability to work as usual. Given the paucity of data, a return to
      patient-derived data will be needed to develop an assessment instrument that is
      able to collect information on headache-related problems in work activities. 

PMID- 24867831
TI  - Migraine in health workers: working in a hospital can be considered an advantage?
AB  - Migraine is the most common form of headache, and is one of the most diffused
      pathologies in the world. Moreover, patients often lose years before obtaining a
      correct diagnosis. The aim of this study was to evaluate whether diagnostic delay
      differs between hospital workers, in theory more sensible to health problems, and
      common people. We compared our cohort of patients attending the headache center
      on which we put a diagnosis of migraine with and without aura with a sample of
      hospital workers investigated about headache presence and characteristics.
      Particularly, hospital workers were evaluated by ID-migraine test, a three
      question test validated to formulate a migraine diagnosis. Continuous variables
      (age and diagnostic delay) were compared with t test for independent samples.
      Dichotomous and categorical variables were compared with Chi squared test. The
      mean difference between in-hospital workers and outpatients was analyzed with a
      GLM/multivariate model accounting for age and sex. The difference between the
      single subcategory of workers affected by migraine was explored with a
      GLM/multivariate model accounting of age and sex. Five hundred and ninety-nine
      patients affected by migraine with and without aura were enrolled. Demographical
      characteristics were comparable in the two study populations. In-hospital workers
      (99 patients) had a mean longer diagnostic delay (14.89 years; 95 % CI: 7.85
      21.93 years) with respect to the outpatients (12.13 years; 95 % CI: 5.37-18.89
      years). The difference resulted statistically significant at the multivariate
      model (p < 0.05). Single subpopulations of in-hospital workers did not have a
      statistically significant different delay in diagnosing migraine. Diagnostic
      delay was significantly longer in hospital workers with respect to outpatients.
      Then, we can conclude that our population of hospital workers did not present a
      particular attention to their headache, probably because of a tendency to self
      treating. Moreover, we did not find differences among different typology of
      workers, underlining that different job experience and education did not
      contribute to a best management of headache. More information and informative
      initiatives are necessary to sensitize people about migraine, especially among
      hospital workers.

PMID- 24867832
TI  - Headache in school age.
AB  - Headache, especially migraine and tension-type headache, is one of the most
      frequently reported somatic complaints by children and adolescents. Different
      population-based studies have been conducted to study the correlation between
      headache and lifestyles in pediatric age, nevertheless, the obtained results are
      often controversial and these relationship still remain unclear. Likewise, is
      still strongly debated the burden of headache during school age, its impact on
      school performances and on quality of life of children and their families.
      Consequently, larger studies are necessary to evaluate the degree of disability
      due to pediatric headache. We summarize the ongoing knowledge about these
      concepts, with the intent to provide useful data to neurologists but also to
      primary care providers, to further improve the management of pediatric headaches
      by preventing the headache progression, the disabling effects associated and
      improving the long-term outcome. 

PMID- 24867833
TI  - Botulinum toxin A: a new option for treatment of chronic migraine with medication
      overuse.
AB  - The application of Botulinum toxin for several pathological conditions has been
      largely debated in the last decades and its use has been definitively
      consolidated for disorders related to increased muscle tone and hyperidrosis.
      Botulinum neurotoxin (BoNT-A) is a potent toxin produced by an anaerobic
      bacterium, Clostridium botulinum, which presents several pharmacological
      proprieties, but also different and serious contraindications. As chronic
      migraine (CM) is commonly reported as a serious and debilitating condition and a
      big challenge from the therapeutic point of view, in the last decades, after
      isolated observations, BoNT-A has been applied as preventive treatment for CM
      patients and, after randomized and rigorous studies, it has been accepted among
      the most effective pharmacological treatments for these problematic patients. In
      the present report, a group of patients suffering from CM with medication overuse
      was treated with BoNT-A to verify its efficacy for CM. The results confirmed the
      efficacy of BoNT-A when used at the dosage of 155 UI, according with the PREEMPT
      study protocol. Although these results are preliminary, in a limited group of
      patients, they led to intense efforts to enforce the use of BoNT-A for CM and to
      assess its clinical applicability.

PMID- 24867834
TI  - Technique of injection of onabotulinumtoxin A for chronic migraine: the PREEMPT
      injection paradigm.
AB  - In 2013 the Italian Pharmacy Agency (AIFA) approved onabotulinumtoxin A injection
      to prevent headaches in adult patients with chronic migraine (headaches on at
      least 15 days per month of which at least 8 days are with migraine) that has not
      responded to at least three prior pharmacological prophylaxis therapies and whose
      condition is appropriately managed for medication overuse. In the present paper
      we report the method of injection of Onabotulinumtoxin A for chronic migraine
      based on the PREEMPT paradigm as described by Blumenfeld et al. (Headache 50:1406
      1418, 2010) adapted to our clinical setting.

PMID- 24867835
TI  - The cost effectiveness of Botox in Italian patients with chronic migraine.
AB  - Migraine is a primary headache which World Health Organization ranks in 19th
      place in the list of disabling diseases. In Europe, in 2004, the total costs for
      migraine were quantified by Stovner and Berg, Eur J Neurol, 12(s1) (2005) at
      <euro>27 billion. The objective of this study is to provide an estimate of the
      incremental cost-effectiveness ratio (ICER) of the treatment of chronic migraine
      with Botox compared to treatment with placebo in the perspective of the Italian
      National Health Service and society. To do this we studied the disease
      progression in a cohort of 688 individuals (patients enrolled in the study
      PREEMPT) via the application of a Markov model. Over a period of 2 years, the
      total costs of the experimental arm of the model amounted to <euro>3,274 compared
      with a gain of 1.34 QALYs. In contrast, the costs of the control arm amounted to
      <euro>2,395 with a gain of 1.24 QALYs. It follows that the incremental costs
      amounted to <euro>889 compared to an incremental gain of 0.09 QALYs in favor of
      the experimental arm. The relationship between costs and incremental QALYs
      generated an ICER of <euro>9,407/QALY. The incremental cost-effectiveness ratio,
      therefore, is favorable compared to the value usually considered by NICE as a
      threshold limit for reimbursement which ranges between <euro>20,000 and
      <euro>40,000/QALY.

PMID- 24867836
TI  - The setting of a botulinum toxin treatment service.
AB  - The administration of botulinum toxin is an activity performed mostly by a
      specialist service for the management of a wide range of neurological conditions.
      For therapeutic purposes botulinum toxin type A is used, although in selected
      patients who develop antibodies specific for the serotype A botulinum toxin B can
      be used for the treatment. Hereby, we describe the organizational arrangements
      for the botulinum toxin treatment service at the Department of Neurology of
      Hospital Cardinal Massaia based in Asti. The diseases most frequently treated are
      movement disorders (primary and secondary focal dystonia, blepharospasm, facial
      emispasmo) spasticity and, more recently, chronic migraine. In particular, the
      latter application is one of the most promising expansions of the use of this
      drug in the few past years, although a larger number of patients are required to
      determine its efficacy and the related tolerability profile.

PMID- 24867837
TI  - The painful muse: migrainous artistic archetypes from visual cortex.
AB  - Neurological diseases which constituted traditionally obstacles to artistic
      creation can, in the case of migraine, be transformed by the artists into a
      source of inspiration and artistic production. These phenomena represent a
      chapter of a broader embryonic neurobiology of painting. 

PMID- 24867838
TI  - Menstrual migraine: treatment options.
AB  - More than half of women with migraine note an association of headache attacks and
      their menstrual cycles. Headaches associated with menses are often more severe
      and disabling than headaches that occur other times of the month. First-line
      therapies include acute agents used for migraine in general; however, for many
      women, these therapies provide incomplete relief. In these situations, treatment
      options include short-term perimenstrual prevention employing nonsteroidal anti
      inflammatory medications, triptans, or hormone-containing preparations. Should
      these options not suffice, or if menstrual cycles are irregular, continuous
      prevention using hormonal therapies or standard anti-migraine prophylaxis should
      be considered. 

PMID- 24867839
TI  - Migraine in pregnancy and lactation.
AB  - Migraine in pregnancy can cause considerable concern to both patient and doctor,
      particularly if migraine starts for the first time during pregnancy or if the
      woman has her first attack with aura. There is often confusion regarding which
      medicines are safe to use during pregnancy and breastfeeding, leaving many women
      unable to control their attacks effectively. This paper reviews the diagnosis as
      well as the management of migraine, which is similar to the non-pregnant state,
      with a few exceptions.

PMID- 24867840
TI  - Migraine and the menopausal transition.
AB  - The menopausal transition or "perimenopause" represents a time period of
      turbulent changes in ovarian hormones as middle-aged women progress into
      menopause. The purpose of this article is to review the literature to determine
      the effect of the menopausal transition on migraine headaches and to develop a
      rational treatment approach to these patients. The menopausal transition is
      divided into early and stages based upon patterns of menstruation and specific
      reproductive hormones. Studies would suggest that the prevalence of migraine and
      other climacteric symptoms tend to peak during the late menopausal transition
      particularly in those with a past history of premenstrual stress disorder.
      Treatment approaches vary by stage of the menopausal transition and include
      conventional daily preventatives, mini-prophylaxis and hormonal therapies.

PMID- 24867841
TI  - Strictly unilateral headaches: considerations of a clinician.
AB  - The aim of the lecture is to draw attention to the role that clinical practice
      and clinical observation have had in stimulating research on the pathophysiology
      of cluster headache (CH) and other trigeminal autonomic cephalalgias (TACs). The
      symptoms of cluster headache-in particular the typical circadian periodicity of
      the headaches and the seasonal recurrence of cluster periods-were fundamental in
      shifting attention away from peripheral pathogenetic hypotheses to the idea that
      cluster headache could have a central origin. Initially, solid
      neuroendocrinological data pointed to hypothalamic involvement. For example, CH
      patients were shown to have alterations in biorhythms. Subsequently, modern
      functional neuroimaging techniques were able to demonstrate that the homolateral
      posterior hypothalamus is activated during TAC headaches, so implicating this
      region in TAC pathogenesis. It is known that the hypothalamus has a modulatory
      effect on nociceptive and autonomic pathways, particularly on the nociceptive
      trigeminovascular system. Future research should clarify whether the hypothalamus
      is the generator of TAC headaches, or whether it is activated in response to an
      alteration of the homeostatic equilibrium between limbic emotional-affective
      components and autonomic-nociceptive components modulated by the hypothalamus.

PMID- 24867842
TI  - Peripheral neurostimulation in primary headaches.
AB  - Peripheral neurostimulation techniques have emerged as promising treatments for
      patients with medically intractable, highly disabling chronic daily headaches
      including chronic migraine (CM) and chronic cluster headache (CCH) besides other
      less common headache syndromes. Encouraging controlled and open label data in
      medically intractable CM and trigeminal autonomic cephalalgias (TACs) have
      suggested a meaningful therapeutic role for occipital nerve stimulation (ONS). In
      view of the frequent occurrence of pain in the first branch of trigeminal nerve,
      percutaneous supraorbital nerve stimulation alone or in combination with ONS has
      been used successfully in open label series of CM and CCH patients. In view of
      its connections with the trigeminovascular system, the stimulation of the
      sphenopalatine ganglion has been used as a therapeutic target for the treatment
      of acute cluster headache attacks, with promising results. Preliminary data in
      patients with epilepsy and migraine have suggested a potential efficacy of vagus
      nerve stimulation in the treatment of primary headaches. Non-invasive devices
      targeting peripheral nerves have been developed and initial experience is
      emerging for the acute and preventive treatments of primary headache disorders.
      This review analyses the available evidence on the efficacy and safety of the
      different peripheral neurostimulation techniques.

PMID- 24867843
TI  - Endonasal mucosal contact points in chronic migraine.
AB  - Some anatomo-functional alterations of the nose may be considered as possible
      causes of headache: deviations of the nasal septum, abnormal turbinates,
      especially middle or superior, with consequent areas of mucosal contact with the
      septum. This study was performed on 100 subjects, 27 chronic migraine (CM)
      sufferers and 73 subjects who never suffered from migraine as control group. In
      the CM group, a direct endoscopic assessment was carried out in order to search
      for mucosal points of contact. Following the endoscopy, the patients underwent a
      computerized tomography (CT) in order to confirm the mucosal contact and for a
      better evaluation of its localization. The control group (C group) consisted of
      subjects who underwent a CT of the skull for various reasons. In CM group, a
      mucosal contact was highlighted in 14 patients (51.8 %); it was unilateral in 50
      % of cases. In C group, the contact was present in 27 cases (36.9 %); in 81.5 %
      of them (n = 22), it was unilateral. A single site of contact was present in 6
      (22 %) patients in CM group and 20 (27.3 %) patients in C group; more sites, in 8
      (29.6 %) CM group patients and in 7 (9.5 %) patients of the C group. The
      connection between subjects and the number of single or multiple contacts in the
      two groups was statistically significant (p = 0.049). Furthermore, the frequency
      of the septum-middle turbinate was significantly (p = 0.0013) more frequent in CM
      sufferers (13/14) compared with control subjects (11/27). This study suggests,
      although with extremely early data, the need to select carefully patients for a
      possible surgical approach, using various parameters: in particular, the site of
      the mucosal contact, favoring the cases with multiple areas of contact, mainly
      between septum-middle turbinate and septum-superior turbinate.

PMID- 24867845
TI  - Gender and triptan efficacy: a pooled analysis of three double-blind, randomized,
      crossover, multicenter, Italian studies comparing frovatriptan vs. other
      triptans.
AB  - Migraine is three times as common in females as in males, and attacks may be more
      severe and difficult to treat in women. However, no study specifically addressed
      possible gender differences in response to antimigraine therapy. The objective of
      this study was to review the efficacy of frovatriptan vs. other triptans, in the
      acute treatment of migraine in subgroups of subjects classified according to
      gender (men vs. women) through a pooled analysis of three individual randomized
      Italian studies. 414 patients suffering from migraine with or without aura were
      randomized to frovatriptan 2.5 mg or rizatriptan 10 mg (study 1), frovatriptan
      2.5 mg or zolmitriptan 2.5 mg (study 2), frovatriptan 2.5 mg or almotriptan 12.5
      mg (study 3). All studies had a multicenter, randomized, double-blind, crossover
      design. After treating 1-3 episodes of migraine in no more than 3 months with the
      first treatment, patients switched to the other treatment for the next 3 months.
      In this analysis, traditional migraine endpoints were compared between the 66 men
      and 280 women of the intent-to-treat population. At baseline, long-term and
      debilitating migraine attacks were more frequently reported by women than men.
      During the observation period, the proportion of pain-free attacks at 2 h did not
      significantly differ between frovatriptan and the comparators in either men (32
      vs. 38 %, p = NS) or women (30 vs. 33 %, p = NS). Pain relief was also similar
      between treatments for both genders (men: 56 % frovatriptan vs. 57 % comparators;
      women: 55 vs. 57 %; p = NS for both). The rate of relapse was significantly lower
      with frovatriptan than with the comparators in men (24 h: 10 vs. 30 %; 48 h: 21
      vs. 39 %; p < 0.05) as well as in women (24 h: 14 vs. 23 %; 48 h: 28 vs. 40 %; p
      < 0.05). The rate of adverse drug reactions was significantly larger with
      comparators, irrespectively of gender. Although migraine presents in a more
      severe form in women, frovatriptan seems to retain its good efficacy and
      favorable sustained antimigraine effect regardless of the gender.

PMID- 24867844
TI  - New treatments for headache.
AB  - Migraine and cluster headache are primary headache disorders commonly encountered
      in clinical practice. Despite the profound disability caused by these primary
      headache disorders, available acute and preventive treatment options are limited.
      Recent understanding of headache pathophysiology has led to the development of
      new drug formulations and novel drug targets that are extremely promising. This
      article will highlight several of the new treatments that are currently under
      investigation including novel delivery mechanisms of already existing
      medications, calcitonin gene-related peptide (CGRP) receptor antagonists,
      antibodies to CGRP and its receptor, serotonin receptor agonists, transient
      receptor potential vanilloid receptor modulators, orexin receptor antagonists,
      glial cell modulators, and neuromodulation. If data is supportive, these
      therapies will be welcome additions to the headache specialist's armamentarium.

PMID- 24867847
TI  - Efficacy of frovatriptan and other triptans in the treatment of acute migraine of
      normal weight and obese subjects: a review of randomized studies.
AB  - An association between obesity and migraine has been observed in recent studies
      and it is supported by plausible biological mechanisms. The objective of this
      study is to evaluate the efficacy of frovatriptan and other triptans in the acute
      treatment of migraine, in patients enrolled in three randomized, double-blind,
      crossover, Italian studies and classified according to body mass index (BMI)
      levels, as normal weight or non-obese (NO, BMI 18.5-24.9 kg/m(2)) and overweight
      or obese subjects (O, BMI >= 25 kg/m(2)). 414 migraineurs with or without aura
      were randomized to frovatriptan 2.5 mg or rizatriptan 10 mg (study 1),
      frovatriptan 2.5 mg or zolmitriptan 2.5 mg (study 2), frovatriptan 2.5 mg or
      almotriptan 12.5 mg (study 3). After treating up to three episodes of migraine in
      3 months with the first treatment, patients switched to the alternate treatment
      for the next 3 months. The present analysis assessed triptan efficacy in 220 N
      and in 109 O subjects of the 346 individuals of the intention-to-treat
      population. The proportion of pain free at 2 h did not significantly differ
      between frovatriptan and the comparators in either NO (30 vs. 34 %) or O (24 vs.
      27 %). However, the rate of pain free at 2 h was significantly (p < 0.05) larger
      in NO than in O, irrespective of the type of triptan. Pain relief at 2 h was also
      similar between drug treatments for either subgroup. Pain relapse occurred at 48
      h in significantly (p < 0.05) fewer episodes treated with frovatriptan in both NO
      (26 vs. 36 %) and O (27 vs. 49 %). The rate of 48-h relapse was similar in NO and
      O with frovatriptan, while it was significantly (p < 0.05) higher in O with the
      comparators. Frovatriptan, in contrast to other triptans, retains a sustained
      antimigraine effect in NO and even more so in O subjects.

PMID- 24867846
TI  - Efficacy of early vs. late use of frovatriptan combined with dexketoprofen vs.
      frovatriptan alone in the acute treatment of migraine attacks with or without
      aura.
AB  - Early triptan use after headache onset may help improve the efficacy of acute
      migraine treatment. This may be particularly the case when triptan therapy is
      combined with a nonsteroidal anti-inflammatory drug (NSAID). The objective of
      this is to assess whether the combination of frovatriptan 2.5 mg + dexketoprofen
      25 or 37.5 mg (FroDex25 and FroDex37.5) is superior to frovatriptan 2.5 mg alone
      (Frova) in the acute treatment of migraine attacks in patients who took the drug
      within 30 min from the onset of pain (early use) or after (late use). A total of
      314 subjects with a history of migraine with or without aura were randomized into
      a double-blind, multicenter, parallel group, pilot study to Frova, FroDex25 or
      FroDex37.5 and were required to treat at least one migraine attack. In the
      present post hoc analysis, traditional migraine endpoints were compared across
      study drugs for subgroups of the 279 patients of the full analysis set according
      to early (n = 172) or late (n = 107) drug use. The proportion of patients pain
      free at 2 h in the early drug use subgroup was 33 % with Frova, 50 % with
      FroDex25 and 51 % with FroDex37.5 mg (p = NS combinations vs. monotherapy), while
      in the late drug use subgroup was 22, 51 and 50 % (p < 0.05 FroDex25 and
      FroDex37.5 vs. Frova), respectively. Pain-free episodes at 4 h were 54 % for
      early and 34 % for late use of Frova, 71 and 57 % with FroDex25 and 74 and 68 %
      with FroDex37.5 (p < 0.05 for early and p < 0.01 for late use vs. Frova). The
      proportion of sustained pain free at 24 h was 26 % under Frova, 43 % under
      FroDex25 mg and 40 % under FroDex37.5 mg (p = NS FroDex25 or 37.5 vs. Frova) in
      the early drug intake subgroup, while it was 19 % under Frova, 43 % under
      FroDex25 mg and 45 % under FroDex37.5 mg (p < 0.05 FroDex25 and FroDex37.5 vs.
      Frova) in the late drug intake subgroup. Risk of relapse at 48 h was similar (p =
      NS) among study drug groups (Frova: 25 %, FroDex25: 21 %, and FroDex37.5: 37 %)
      for the early as well as for the late drug use subgroup (14, 42 and 32 %). FroDex
      was found to be more effective than Frova taken either early or late. The
      intrinsic pharmacokinetic properties of the two single drug components made
      FroDex combination particularly effective within the 2-48-h window from the onset
      of the acute migraine attack. The efficacy does not seem to be influenced by the
      time of drug use relative to the onset of headache.

PMID- 24867848
TI  - Biofeedback and behavioral treatments: filling some gaps.
AB  - Biofeedback and related behavioral approaches have been employed for decades in
      the management of recurrent headache conditions, with ample evidence to support
      their clinical utility. Initially, these treatments were employed entirely in the
      office and required an extended number of face-to-face sessions. Researchers have
      entered a new era wherein they are focusing on ways to make these treatments less
      intensive on the part of therapists, less expensive on the part of patients, more
      widely available and accessible, and retain their level of effectiveness. Initial
      efforts have focused on PLOT, group, internet, and mass media delivery
      approaches. This article discusses further approaches being explored to continue
      to extend behavioral treatment options for patients, focusing on alternative
      approaches for managing headaches, discussing the value of exercise, addressing
      depression and sleep problems more directly, and incorporating techniques of
      motivational interviewing. The importance, role, and value of patient education
      are stressed throughout. 

PMID- 24867849
TI  - Effects of the acupoints PC 6 Neiguan and LR 3 Taichong on cerebral blood flow in
      normal subjects and in migraine patients.
AB  - Acupuncture has been proven to be effective in the treatment of various
      cardiovascular disorders; it acts both on the peripheral flow and on the cerebral
      flow. Our study aimed to evaluate the effects of the insertion of PC 6 Neiguan
      and LR 3 Taichong acupoints on the cerebral blood flow (CBF) in the middle
      cerebral artery (MCA). These effects were measured in a group of patients
      suffering from migraine without aura (Group M) and in a healthy control group
      (Group C). In the study, we included 16 patients suffering from migraine without
      aura, classified according to the criteria of the International Headache Society,
      and 14 healthy subjects as a control group. The subjects took part in the study
      on two different days, and on each day, the effect of a single acupoint was
      evaluated. Transcranial Doppler was used to measure the blood flow velocity (BFV)
      in the MCA. Our study showed that the stimulation of PC 6 Neiguan in both groups
      results in a significant and longlasting reduction in the average BFV in the MCA.
      After pricking LR 3 Taichong, instead, the average BFV undergoes a very sudden
      and marked increase; subsequently, it decreases and tends to stabilize at a
      slightly higher level compared with the baseline, recorded before needle
      insertion. Our data seem to suggest that these two acupoints have very different
      effects on CBF. The insertion of PC 6 Neiguan probably triggers a vasodilation in
      MCA, while the pricking of LR 3 Taichong determines a rapid and marked
      vasoconstriction.

PMID- 24867852
TI  - Complementary and alternative medicine (CAM) use in an Italian cohort of
      pediatric headache patients: the tip of the iceberg.
AB  - The use of complementary alternative medicine (CAM) in paediatric populations is
      considerably increased, especially for pain and chronic conditions, as
      demonstrated by epidemiological surveys both in Europe and in the USA. In our
      study, CAM was used in 76 % patients of a cohort of 124 children affected by
      headache (age 4-16 years; 67 % female; 70 % migraine without aura, 12 % migraine
      with aura, 18 % tensive headache according to IHS criteria) consecutively
      recruited at a Pediatric Headache University Center. CAM was used as preventive
      treatment in 80 % cases. The main reasons for seeking CAM were: the wish of
      avoiding chronic use of drugs with their related side effects, the desire of an
      integrated approach, the reported inefficacy of conventional medicine, and a more
      suitable children disposition to CAM than to pharmacological compound. Female
      gender, younger age, migraine without aura, parents' higher educational status,
      maternal use of CAM and other associated chronic conditions, correlated with CAM
      use (p < 0.05). 73 % patients chose CAM also to treat other diseases (i.e.
      allergies, colitis, asthma, insomnia, muscle-scheletric disorders and
      dysmenorrhoea). The most assumed CAM were: herbal remedies (64 %) such as
      Valeriana, Ginkgo biloba, Boswellia serrata, Vitex agnus-castus, passion flower,
      Linden tree; vitamins/minerals supplements (40 %) with magnesium, 5
      Hydroxytryptophan, vitamin B6 or B12, Multivitamin compounds; Homeopathy (47 %)
      with Silicea, Ignatia Amara, Pulsatilla, Aconitum, Nux Vomica, Calcarea
      phosphorica; physical treatment (45 %) such as Ayurvedic massage, shiatsu,
      osteopathy; yoga (33 %); acupuncture (11 %). CAM-often integrated with
      conventional care-was auto-prescribed in 30 % of the cases, suggested by non
      physician in 22 %, by the General Practitioner in 24 % and by paediatrician in 24
      %. Both general practitioners and neurologists were mostly unaware of their
      patients' CAM use. In conclusion, neurologists should inquire for CAM use and be
      prepared to learn about CAM therapies or to directly interact with CAM trained
      experts, in order to coordinate an integrative approach to health, as especially
      required in paediatric headache patients and their parents. Further studies are
      required to investigate safety and efficacy of CAM in pediatric headache, as a
      possible side-medicine to conventional pharmacological approach.

PMID- 24867853
TI  - Higher burden of migraine compared to other neurological conditions: results from
      a cross-sectional study.
AB  - Headache disorders are prevalent, burdensome and costly. However, it is difficult
      to get an idea of how much of a burden do they cause if they are not compared
      with other conditions. Using data from PARADISE project, we compared 80
      migraineurs and 80 patients similar for age, gender and work condition. Our
      results showed that the amount of psycho-social difficulties was higher among
      patients with migraine than among patients with epilepsy, stroke, multiple
      sclerosis or Parkinson's disease.

PMID- 24867850
TI  - Herbal therapy in migraine.
AB  - The use of herbal therapies is ancient and increasing worldwide. There is a
      growing body of evidence supporting the efficacy of various "complementary" and
      alternative medicine approaches in the management of headache disorders.
      Promising tools to treat migraine patients are herbal products. In particular
      constituents of Petasites hybridus, Tanacetum Parthenium and Ginkgo Biloba have
      shown antimigraine action in clinical studies. A miscellaneous of recreational
      drugs and other herbal remedies have been supposed to have a role in headache
      treatment but quality of clinical studies in this field is low and inconclusive.
      Further research is warranted in this area. 

PMID- 24867851
TI  - Riboflavin and migraine: the bridge over troubled mitochondria.
AB  - Brain energy metabolism has been found to be disturbed in migraine. A
      mitochondrial defect may reduce the threshold for migraine attacks both
      increasing neuronal excitability and leading migrainous brain to a hyper
      responsiveness to triggering stimuli. Riboflavin, a major co-factor in oxidative
      metabolism, may overcome this impairment. RCT studies in adult confirmed that
      riboflavin is safe and probably effective in migraine prophylaxis, based on level
      B evidence. Improving brain energy metabolism may reduce the susceptibility to
      migraine when brain energy demand increases due to both physiological and
      biopsychological factors. 

PMID- 24867854
TI  - Post-traumatic headaches: a clinical overview.
AB  - Headache attributed to head and/or neck trauma or injury, the so-called post
      traumatic headache (PTH), is the most common secondary headache disorder and one
      of the most controversial clinical entities in the headache field, due to its
      unclear pathophysiological mechanisms and the unsolved role of associated
      psychological and medico-legal aspects. PTH, as a significant cause of morbidity
      after traumatic brain injury, may occur as an isolated symptom or as one of a
      constellation of symptoms known as post-concussive syndrome. However, in many
      cases, PTH might also represent an accentuation of non-disabling, remote or
      infrequent pre-existing primary headaches rather than a new onset headache
      strictly related to the trauma. Recently, the International Classification of
      Headache Disorders attempted to classify PTH; however, many unsolved issues are
      still to be clarified. In this brief review, we will focus on PTH clinical
      aspects and diagnostic criteria. 

PMID- 24867855
TI  - Headache in a population of hospital workers.
AB  - Headache prevalence is very high, especially during working life. Hospital
      workers are expected to be particularly careful with health problems. Few data
      are available about the dimension of the headache-related problems among hospital
      workers, including disease awareness and diagnostic delay. 502 subjects employed
      in our hospital (doctors, nurses, technicians, administrative employees) were
      enrolled over a 3-month period and submitted to a questionnaire about the
      presence of headache, its characteristics and time spent from disease onset to
      diagnosis. We used the ID-migraine test, a validated tool, to obtain a correct
      migraine diagnosis based on a three-question test. Age and education were
      collected as continuous variables while the other variables (sex, presence of
      headache, presence of migraine, diagnosis put by the general practitioners) were
      encoded as binary. The difference of the distribution of the analyzed variables
      in tables was evaluated with chi (2) test. The data were analyzed with SPSS 13.0
      for Windows systems. In the analyzed population (mean age 40.15 +/- 11.0 years;
      males 60.7 %), 216 patients complained of headache (43.1 %) and 77 (15.4 %) were
      diagnosed as migraineous at the in-hospital evaluation. Among the 216 cephalalgic
      patients, the majority (59.7 %, p < 0.0001 at chi (2) test) did not refer to
      their general practitioner. Of the 77 patients affected by migraine, 55.8 %
      referred to their general practitioner, but only 27 (35.1 %) received a definite
      migraine diagnosis. Fifty subjects (64.9 %) were still undiagnosed and
      unevaluated at the moment of our survey (p < 0.0001 at chi (2) test). Headache
      prevalence was very high in this population of hospital workers. Diagnostic
      errors and delays were frequent. Unexpectedly, self-awareness of the headache was
      very low. Headache, particularly migraine, is a relevant cause of loss of working
      days and low productivity. Our findings suggest the necessity to program
      initiatives aimed to raise the awareness of headache in order to improve
      diagnostic and therapeutic possibilities.

PMID- 24867856
TI  - Relationship between primary headache and nutrition: a questionnaire about
      dietary habits of patients with headache.
AB  - The role of food associated with the headache has been the subject of scientific
      research since 1900, especially for migraine patients. A substantial proportion
      of patients (ranging from 12 to 60 %) report that their migraine attacks may be
      precipitated by dietary elements, certain eating habits (fasting) and abuse
      (caffeine and alcoholic beverages abuse and withdrawal). The biological mechanism
      by means of triggers in general and food in particular precipitate migraine
      attacks remains obscure. Based on the data in the literature, we performed an
      osservational study searching for possible correlations between nutrition and
      primary headaches. We enrolled 50 consecutive patients from the Headache Center
      of the Neurology Department of Hospital "Cardinal Massaia" of Asti and submitted
      them a 14-item questionnaire for the assessment of relationship between primary
      headache and food. Our preliminary data, although the follow up is still in
      progress, show that there are strong associations between the onset of the
      headache and dietary habits. It will be necessary to analyze a larger sample in
      order to draw more precise conclusions on this topic.

PMID- 24867857
TI  - The increased distensibility of the wall of cerebral arterial network may play a
      role in the pathogenic mechanism of migraine headache.
AB  - The aim was to evaluate whether patients with episodic migraine with (MA+) and
      without aura (MA-), during the interictal period of migraine would have an
      altered distensibility of the wall of cerebral arterial network and whether it
      would play a role in migraine headache. To evaluate the distensibility of the
      wall of cerebral arterial network, we measured the time-delay in milliseconds
      (ms) between the R-wave of an electrocardiogram and the arterial pulse wave of
      cerebral microcirculation (R-APWCMtd) on the frontal cortex detected by near
      infrared spectroscopy (NIRS) in 10 patients with MA+ (age 39.5 +/- 12.2 years),
      in 10 with MA- (age 40.3 +/- 10.2 years), according to ICHD-3 criteria 2012,
      during the interictal period of migraine, and in 15 age-, sex- and height-matched
      healthy control subjects. The patients with migraine had a significantly longer R
      APWCMtd than the control subjects F = 13.4, p < 0.001: MA+:+38.3 ms; MA-:+34.7 ms
      indicating an increased distensibility of the wall of cerebral arterial network.
      In multiple regression analysis, R-APWCMtd was significantly associated with
      migraine (R (2) = 0.50, p < 0.0001) but not with age, gender, height, migraine
      attack frequency and disease duration. The increased distensibility leads to an
      increased flow pulsatility into intracranial dural meningeal vessels that may
      lead to a mechanical stimulation of the nociceptors that innervate the dural
      vasculature. This condition may play a role in promoting the sensitization of
      trigeminovascular afferents and sterile inflammation within the dura mater that
      are fundamental to the pathogenesis of migraine headache.

PMID- 24867858
TI  - Is the brain of migraineurs "different" even in dreams?
AB  - Migraineurs brain is hyper-excitable and hypo-metabolic. Dreaming is a mental
      state characterized by hallucinatory features in which imagery, emotion, motor
      skills and memory are created de novo. To evaluate dreams in different kinds of
      headache. We included 219 controls; 148 migraineurs (66 with aura-MA, 82 without
      aura-MO); 45 tension type headache (TTH) patients. ICHD-II diagnostic criteria
      were used. Ad hoc questionnaire was used to evaluate oneiric activity. The
      Generalized Anxiety Disorder Questionnaire, and the Patient Health Questionnaire
      were administered to evaluate anxiety and mood. The prevalence of dreamers was
      similar in different groups. Frequency of visual and auditory dreams was not
      different between groups. Migraineurs, particularly MA, had an increased
      frequency of taste dreams (present in 19.6 % of controls, 40.9 % of MA, 23.2 % of
      MO, 11.1 % of TTH, p < 0.01), and of olfactory dreams (present in 20 % of
      controls, 36 % of MA, 35 % of MO and 20 % of TTH, p < 0.01). Anxiety and mood did
      not influence these results. The increased frequency of taste and olfactory
      dreams among migraineurs seems to be specific, possibly reflecting a particular
      sensitivity of gustative and olfactory brain structures, as suggested by
      osmofobia and nausea, typical of migraine. This may suggest the role of some
      cerebral structures, such as amygdala and hypothalamus, which are known to be
      involved in migraine mechanisms as well in the biology of sleep and dreaming.

PMID- 24867859
TI  - Evaluation of immune parameters in chronic migraine with medication overuse.
AB  - It has been postulated that chronic pain and chronic migraine in particular, can
      be connected to immunologic disturbances. Moreover the psychiatric comorbidity is
      often responsible of migraine chronification, but also of developing of
      particular immune function alterations. The role of the immune system in migraine
      precipitation is still under debate also if speculations about the evidence of
      infections in migraine patients has been performed, but not always corroborated
      by clinical and scientific explanations. In this report we present an evaluation
      of specific immune parameters in patients suffering from different forms of
      migraine respect to controls in order to determine possible alterations in immune
      function: speculations about the evidenced abnormalities are attempted. 

PMID- 24867860
TI  - Onabotulinumtoxin A for prophylaxis in chronic migraine: preliminary data from
      Headache Regional Centre of Aosta Valley.
AB  - Chronic migraine (CM) is a complex neurological disorder associated with
      substantial disability that affects approximately 2 % of general population.
      Onabotulinumtoxin A is employed for patients suffering from CM refractory to
      common therapeutic prophylaxis. Since May 2013, we have selected 22 patients
      referring to our headache centre with a history of CM which meets the diagnostic
      criteria of ICHD-3 beta (2013). The patients have been treated with
      onabotulinumtoxin A injection in 31 sites according to the protocol of the
      PREEMPT study at the total dosage of 155 U/treatment every 3 months. So far,
      eight patients have been subjected to three treatment sessions, five patients to
      two treatments and nine patients to one treatment. Three patients dropped for low
      compliance, but there were no serious adverse events. The frequency of headache
      days, the intensity of headache and the headache disability have been measured
      using headache diary, migraine disability assessment (MIDAS) questionnaire and
      headache impact test (HIT)-6 score. Data concerning the 13 patients who have been
      submitted to at least two treatment sessions have already shown a decrease of
      headache days of 20.64 % after the first treatment; MIDAS and HIT-6 scores have
      been significantly improved with a reduction of the scores, respectively, of
      38.45 % for MIDAS and of 6.95 % for HIT-6. These are preliminary results because
      the observation time, the number of treatment sessions and the number of patients
      treated are still few.

PMID- 24867861
TI  - Intracranial idiopathic hypertension: 1-year follow-up study.
AB  - Standard guidelines for ongoing management, as well as definitive data about the
      long-term course of idiopathic intracranial hypertension (IIH) are not available.
      The aim of this study was to compare several clinical and instrumental variables
      as assessed at the time of diagnosis and then after 1 year in a sample of IIH
      patients. A total of 21 patients were studied. Our results confirmed that
      headache and TVO are the most frequent symptoms in IIH patients, and that
      overweight is a very common feature. A trend towards a favorable outcome in
      patients followed for 1 year and treated by usual medical therapy was found:
      intracranial pressure was lower at follow-up; improvement of headache and
      transient visual obscurations, as well as of papilledema, was reported in most
      patients. On the other hand, neuroradiological findings (such as empty sella,
      perioptic subarachnoid space distension, narrowing of the transverse sinuses)
      were substantially stable at follow. These findings may be relevant for future
      research as far as understanding the role of different clinical and instrumental
      findings as diagnostic items as well as predictors of outcome in IIH.

PMID- 24867862
TI  - Recurrent epistaxis following stabbing headache responsive to acetazolamide.
AB  - The co-occurrence of epistaxis and headache is not uncommon in migraine patients,
      although only few case reports have been published. A trigeminovascular
      activation may be causally involved although the exact mechanisms linking
      epistaxis and migraine remain unclear. Significant dural sinus stenosis may
      sustain or worsen an increased cerebral venous pressure and is considered a
      radiological predictor of idiopathic intracranial hypertension. We report a 49
      year-old female patient with chronic migraine associated to stabbing headache
      like attacks followed by epistaxis and by the resolution or the significant
      improvement of pain. As she also reported adjunctive symptoms suggestive of
      raised intracranial pressure and showed a bilateral narrowing of transverse
      sinuses at MR-venography, a possible intracranial hypertension was hypothesized
      despite the lack of papilledema. Acetazolamide 250 mg twice/day was added to
      therapy and the patient reported sudden reduction of headache severity and
      frequency and complete resolution of both the stabbing pain and the recurrent
      epistaxis, maintained for 5 months. At treatment discontinuation she complained
      the worsening of migraine headache and the reoccurrence of the superimposed
      stabbing pain followed by epistaxis. The mechanism linking the sequential
      occurrence of painful stabs, epistaxis and relief from pain with raised
      intracranial pressure in our patients remains unclear. We speculate that the
      sudden reopening of collapsed collateral veins of the anterior venous circle,
      possibly prompted by periodic waves of central venous hypertension coupled with
      intracranial hypertensive peaks, could explain the unusual strict time succession
      of painful stabs, epistaxis, and subsequent resolution of pain.

PMID- 24867863
TI  - Prevalence and profile of obsessive-compulsive trait in patients with chronic
      migraine and medication overuse.
AB  - Patients with chronic migraine (CM) and medication overuse headache (MOH) have
      high frequency of psychiatric comorbidity or psychopathological traits, the
      presence of which can influence the clinical course. The presence of subclinical
      obsessive compulsive disorder (OCD) is underestimated in migraine patients. The
      aim of this study was to estimate the prevalence and profile of obsessive
      compulsive (OBS) trait in a sample of CM patients with MOH using the OBS
      questionnaire of Spectrum Collaborative Project. According to the new
      international classification of headache disorders (ICHD-III beta) criteria, 106
      patients (15 M, 91 F, mean age 47.3 years) were selected in a consecutive
      clinical series. Our results showed that 36 % of patients with CM and MOH were
      positive at OBS-questionnaire. As far as the profile of OBS trait, we performed
      an evaluation of prevalence of items separating the first part of the
      questionnaire (childhood/adolescence and doubts in lifetime) from the other five
      domains: 21 % of the patients showed prevalence of items in childhood/adolescence
      domain; 79 % in doubts in lifetime domain; as for other five domains, 10.5 % of
      patients had prevalence of pathological answers among hypercontrol, 5.2 % in
      spending time, 23.7 % in perfectionism, 29 % in repetition and automation, and
      31.5 % in specific themes (obsessive thoughts). The presence of subclinical OCD
      in migraine patients, and the link between progression to CM, particularly
      through MO, and OBS trait is still not well defined. The use of specific tools to
      assess this possible comorbidity should be encouraged in clinical and research
      settings.

PMID- 24867864
TI  - Ear acupuncture and fMRI: a pilot study for assessing the specificity of
      auricular points.
AB  - In recent years research explored different acupuncture stimulation techniques
      but interest has focused primarily on somatic acupuncture and on a limited number
      of acupoints. As regards ear Acupuncture (EA) there is still some criticism about
      the clinical specificity of auricular points/areas representing organs or
      structures of the body. The aim of this study was to verify through (Functional
      magnetic resonance imaging) fMRI the hypothesis of EA point specificity using two
      auricular points having different topographical locations and clinical
      significance. Six healthy volunteers underwent two experimental fMRI sessions:
      the first was dedicated to the stimulation of Thumb Auricular Acupoint (TAA) and
      the second to the stimulation of Brain Stem Auricular Acupoint (BSAA). The
      stimulation of the needle placed in the TAA of the left ear produced an increase
      in activation bilaterally in the parietal operculum, region of the secondary
      somatosensory area SII. Stimulation of the needle placed in the BSAA of the left
      ear showed a pattern that largely overlapped regions belonging to the pain
      matrix, as shown to be involved in previous somatic acupuncture studies but with
      local differences in the left amygdala, anterior cingulate cortex, and
      cerebellum. The differences in activation patterns between TAA and BSAA
      stimulation support the specificity of the two acupoints. Moreover, the
      peculiarity of the regions involved in BSAA stimulation compared to those
      involved in the pain matrix, is in accordance with the therapeutic indications of
      this acupoint that include head pain, dizziness and vertigo. Our results provide
      preliminary evidence on the specificity of two auricular acupoints; further
      research is warranted by means of fMRI both in healthy volunteers and in patients
      carrying neurological/psychiatric syndromes. 

PMID- 24867865
TI  - Acupuncture in cluster headache: four cases and review of the literature.
AB  - Although cluster headache (CH) is the most disabling form of primary headache,
      little evidences regarding alternative and complementary therapies are available.
      Only few dated studies and some isolated cases are described. We describe four
      patients with CH treated with acupuncture as a preventive treatment, combined
      with verapamil or alone. All patients received acupuncture treatment twice/week
      for 2 weeks, then once/week for 8 weeks, and then once/alternate weeks for 2
      weeks. According to Traditional Chinese Medicine the acupoints selected were: Ex
      HN-5 Taiyang, GB 14 Yangbai (both only on the affected side), GB 20 Fengchi (on
      both sides), LI 4 Hegu, LR 2 Xingjiang, SP 6 Sanyinjiao, ST 36 Zusanli (all on
      both sides). At each point, after the insertion of the needle, the feeling of "De
      Qi" was evoked; after obtaining this sensation the acupoints were not further
      stimulated for a period of 20 min, until their extraction. In all patients an
      interruption of cluster attacks was obtained. To our knowledge, this is the first
      report concerning acupuncture in CH patients which details the protocol approach,
      acupoints and duration of the treatment. Our results offer the opportunity to
      discuss the emerging role of acupuncture in the therapy of CH, assuming a
      possible influence on opioid system.

PMID- 24867866
TI  - Study of parafunctions in patients with chronic migraine.
AB  - The purpose of this paper is to present the results of a questionnaire
      investigating parafunctions (particularly clenching and grinding) in patients
      with chronic migraine presenting sign of temporomandibular disorder. The
      questionnaire was elaborated by the Dental Clinic of the University of Milano and
      completed by 125 patients experiencing chronic migraine and attending the
      Neurological Institute Carlo Besta for an inpatient withdrawal protocol to treat
      medication overuse. Our results showed high percentages of parafunctions, which
      were present in 80 % of patients. We note that patient information on possible
      behaviours and coexisting conditions which may be involved in the mechanisms of
      chronic headaches, as well as education about these factors, are crucial aspects
      in the management of chronic headache patients. We suggest that patients
      suffering from chronic migraine with medication overuse headache should be
      evaluated in relation to the possible presence of parafunctions, and as far as
      the need for interocclusal devices, in order to limit the role of
      temporomandibular dysfunctions as trigger factors or coexisting conditions
      favouring the development/maintaining of headache chronification.

PMID- 24867867
TI  - Post-traumatic headaches: an epidemiological overview.
AB  - Post-traumatic headache (PTH) is the most common secondary headache disorder,
      corresponding to approximately 4 % of all symptomatic headaches. PTH, a cardinal
      feature of the post-concussive syndrome, usually shows a phenotype similar to
      migraine or tension-type headache. However, rare cases of PTH similar to
      trigeminal autonomic cephalalgias have been described. Many studies have
      investigated PTH prevalence and potential risk factors for its development and
      maintenance. In general population, the majority of PTH patients is female and
      has been involved in vehicle-related accidents. Generally, headache gradually
      disappears over few weeks or months; however, PTH could become persistent and
      very disabling in a minority of patients. This brief review will focus on PTH
      epidemiological aspects.

PMID- 24867868
TI  - Sex-related differences in migraine.
AB  - This paper reviews sex-related differences in migraine epidemiology, symptoms,
      natural history and co-morbid disorders. Migraine is more than twice as common in
      females as in males, and women experience more frequent, longer lasting and more
      painful attacks, have more disability and a risk of transition from episodic to
      chronic migraine greater than men, but the mechanisms behind these differences
      are still poorly understood. The role of sex hormones, genes, and the differences
      in brain function and structure are discussed. Finally, we evaluate the many
      gender-related questions about treatment of migraine in women. In future research
      data should be analyzed separately for men and women to ensure that differences
      between the sexes could be identified. 

PMID- 24867871
TI  - Highly selective water adsorption in a lanthanum metal-organic framework.
AB  - We present a new metal-organic framework (MOF) built from lanthanum and pyrazine
      2,5-dicarboxylate (pyzdc) ions. This MOF, [La(pyzdc)1.5(H2O)2]?2 H2O, is
      microporous, with 1D channels that easily accommodate water molecules. Its
      framework is highly robust to dehydration/hydration cycles. Unusually for a MOF,
      it also features a high hydrothermal stability. This makes it an ideal candidate
      for air drying as well as for separating water/alcohol mixtures. The ability of
      the activated MOF to adsorb water selectively was evaluated by means of
      thermogravimetric analysis, powder and single-crystal X-ray diffraction and
      adsorption studies, indicating a maximum uptake of 1.2 mmol g(-1) MOF. These
      results are in agreement with the microporous structure, which permits only water
      molecules to enter the channels (alcohols, including methanol, are simply too
      large). Transient breakthrough simulations using water/methanol mixtures confirm
      that such mixtures can be separated cleanly using this new MOF.

PMID- 24867869
TI  - Development of spatial integration depends on top-down and interhemispheric
      connections that can be perturbed in migraine: a DCM analysis.
AB  - In humans, spatial integration develops slowly, continuing through childhood into
      adolescence. On the assumption that this protracted course depends on the
      formation of networks with slowly developing top-down connections, we compared
      effective connectivity in the visual cortex between 13 children (age 7-13) and 14
      adults (age 21-42) using a passive perceptual task. The subjects were scanned
      while viewing bilateral gratings, which either obeyed Gestalt grouping rules
      [colinear gratings (CG)] or violated them [non-colinear gratings (NG)]. The
      regions of interest for dynamic causal modeling were determined from activations
      in functional MRI contrasts stimuli > background and CG > NG. They were
      symmetrically located in V1 and V3v areas of both hemispheres. We studied a
      common model, which contained reciprocal intrinsic and modulatory connections
      between these regions. An analysis of effective connectivity showed that top-down
      modulatory effects generated at an extrastriate level and interhemispheric
      modulatory effects between primary visual areas (all inhibitory) are
      significantly weaker in children than in adults, suggesting that the formation of
      feedback and interhemispheric effective connections continues into adolescence.
      These results are consistent with a model in which spatial integration at an
      extrastriate level results in top-down messages to the primary visual areas,
      where they are supplemented by lateral (interhemispheric) messages, making
      perceptual encoding more efficient and less redundant. Abnormal formation of top
      down inhibitory connections can lead to the reduction of habituation observed in
      migraine patients.

PMID- 24867873
TI  - Sonographic findings and perinatal outcome of multiple pregnancies associating a
      complete hydatiform mole and a live fetus: a case series.
AB  - BACKGROUND: The aim of this case series was to present the ultrasonographic
      findings, clinical features, management, and outcome of multiple pregnancies with
      complete hydatidiform mole and coexisting fetus (CHMCF). METHODS: Sonographic
      features and obstetrical and perinatal outcomes of seven cases with CHMCF were
      analyzed retrospectively. RESULTS: A total of seven cases was included in the
      analysis. Six cases were twins and one case was quadruplet. The mean +/- SD
      maternal age was 25.3 +/- 1.9 years (median: 25; range: 23-29). The mean
      gestational age at diagnosis was 16.1 +/- 4.6 weeks (median: 17; range: 11-23).
      Two pregnancies were achieved by ovulation induction. Two couples opted for
      pregnancy termination. Four pregnancies resulted in fetal loss between the 11th
      and 23th week of gestation. One pregnancy ended with the preterm delivery of a
      live-born neonate at 34 weeks due to pre-eclampsia. One patient developed
      persistent trophoblastic disease, which was treated by hysterectomy. The mean +/-
      SD time for beta-human chorionic gonadotropin clearance was 3.7 +/- 0.5 weeks
      (median: 4; range: 3-4) in the six patients without persistent trophoblastic
      disease. CONCLUSIONS: Spontaneous fetal loss is the most likely outcome for
      CHMCF. However, on the basis of our experience, we recommend carefully monitored
      continuation of pregnancy as long as maternal complications are not present or
      are controllable.

PMID- 24867872
TI  - Gestational stage affects amniotic epithelial cells phenotype, methylation
      status, immunomodulatory and stemness properties.
AB  - Stem cells isolated from amniotic epithelium (AECs) have shown great potential in
      cell-based regenerative therapies. Because of their fetal origin, these cells
      exhibit elevated proliferation rates and plasticity, as well as, immune tolerance
      and anti-inflammatory properties. These inherent attitudes make AECs well-suited
      for both allogenic and xenogenic cellular transplants in animal models. Since in
      human only at term amnion is easily obtainable after childbirth, limited
      information are so far available concerning the phenotypic and functional
      difference between AECs isolated from early and late amnia. To this regard, the
      sheep animal model offers an undoubted advantage in allowing the easy collection
      of both types of AECs in large quantity. The aim of this study was to determine
      the effect of gestational age on ovine AECs (oAECs) phenotype, immunomodulatory
      properties, global DNA methylation status and pluripotent differentiation ability
      towards mesodermic and ectodermic lineages. The immunomodulatory property of
      oAECs in inhibiting lymphocyte proliferation was mainly unaffected by gestational
      age. Conversely, gestation considerably affected the expression of surface
      markers, as well the expression and localization of pluripotency markers. In
      detail, with progression of gestation the mRNA expression of NANOG and SOX2
      markers was reduced, while the ones of TERT and OCT4A was unaltered; but at the
      end of gestation NANOG, SOX2 and TERT proteins mainly localized outside the
      nuclear compartment. Regarding the differentiation ability, LPL (adipogenic
      specific gene) mRNA content significantly increased in oAECs isolated from early
      amnia, while OCN (osteogenic-specific gene) and NEFM (neurogenic-specific gene)
      mRNA content significantly increased in oAECs isolated from late amnia,
      suggesting that gestational stage affected cell plasticity. Finally, the degree
      of global DNA methylation increased with gestational age. All these results
      indicate that gestational age is a key factor capable of influencing
      morphological and functional properties of oAECs, and thus probably affecting the
      outcome of cell transplantation therapies. 

PMID- 24867875
TI  - Effects of restoring portal flow with anticoagulation and partial splenorenal
      shunt embolization.

PMID- 24867874
TI  - Myeloid-lymphoid ontogeny in the rhesus monkey (Macaca mulatta).
AB  - Establishment of a functional immune system has important implications for health
      and disease, yet questions remain regarding the mechanism, location, and timing
      of development of myeloid and lymphoid cell compartments. The goal of this study
      was to characterize the ontogeny of the myeloid-lymphoid system in rhesus monkeys
      to enhance current knowledge of the developmental sequence of B-cell (CD20,
      CD79), T-cell (CD3, CD4, CD8, FoxP3), dendritic cell (CD205), and macrophage
      (CD68) lineages in the fetus and infant. Immunohistochemical assessments
      addressed the temporal and spatial expression of select phenotypic markers in the
      developing liver, thymus, spleen, lymph nodes, gut-associated lymphoid tissue
      (GALT), and bone marrow with antibodies known to cross-react with rhesus cells.
      CD3 was the earliest lymphoid marker identified in the first trimester thymus
      and, to a lesser extent, in the spleen. T-cell markers were also expressed
      midgestation on cells of the liver, spleen, thymus, and in Peyer's patches of the
      small and large intestine, and where CCR5 expression was noted. A myeloid marker,
      CD68, was found on hepatic cells near blood islands in the late first trimester.
      B-cell markers were observed mid-second trimester in the liver, spleen, thymus,
      lymph nodes, bone marrow spaces, and occasionally in GALT. By the late third
      trimester and postnatally, secondary follicles with germinal centers were present
      in the thymus, spleen, and lymph nodes. These results suggest that immune
      ontogeny in monkeys is similar in temporal and anatomical sequence when compared
      to humans, providing important insights for translational studies.

PMID- 24867876
TI  - Trypanocidal drugs for chronic asymptomatic Trypanosoma cruzi infection.
AB  - BACKGROUND: Prevention of chronic chagasic cardiomyopathy (CCC) by treating
      infected populations with trypanocidal therapy (TT) remains a challenge. Despite
      a renewed enthusiasm for TT, uncertainty regarding its efficacy, concerns about
      its safety and limited availability remain barriers for a wider use of
      conventional drugs. We have updated a previous version of this review.
      OBJECTIVES: To systematically search, appraise, identify and extract data from
      eligible studies comparing the outcome of cohorts of seropositive individuals to
      Trypanosoma cruzi exposed to TT versus placebo or no treatment. SEARCH METHODS:
      We sought eligible studies in electronic databases (Cochrane Central Register of
      Controlled Trials (CENTRAL), Issue 1, 2014); MEDLINE (Ovid, 1946 to January week
      5 2014); EMBASE (Ovid, 1980 to 2014 week 6) and LILACS (up to 6 May 2010)) by
      combining terms related with the disease and the treatment. The search also
      included a Google search, handsearch for references in review or selected
      articles, and search of expert files. We applied no language restrictions.
      SELECTION CRITERIA: Review authors screened the retrieved references for
      eligibility (those dealing with human participants treated with TT) and then
      assessed the pre-selected studies in full for inclusion. We included randomised
      controlled trials (RCTs) and observational studies that provided data on either
      mortality or clinical progression of CCC after at least four years of follow-up.
      DATA COLLECTION AND ANALYSIS: Teams of two review authors independently carried
      out the study selection, data extraction and risk of bias assessment, with a
      referee resolving disagreement within the pairs. Data collection included study
      design, characteristics of the population and interventions or exposures and
      outcome measures. We defined categories of outcome data as parasite-related
      (positive serology, xenodiagnosis or polymerase chain reaction (PCR) after TT)
      and participant-related (including efficacy outcomes such as progression towards
      CCC, all-cause mortality and side effects of TT). We reported pooled outcome data
      as Mantel-Haenszel odds ratios (OR) or standardised mean differences (SMD) along
      with 95% confidence intervals (CI), using a random-effects model. I(2) statistics
      provided an estimate of heterogeneity across studies. We conducted an exploratory
      meta-regression analysis of the relationship between positive-serology and
      progression of CCC or mortality. MAIN RESULTS: We included 13 studies involving
      4229 participants (six RCTs, n = 1096, five RCTs of intermediate risk of bias,
      one RCT of high risk of bias; four non-randomised experiments, n = 1639 and three
      observational studies, n = 1494). Ten studies tested nitroderivative drugs
      nifurtimox or benznidazole (three exposed participants to allopurinol, one to
      itraconazole). Five studies were conducted in Brazil, five in Argentina, one in
      Bolivia, one in Chile and one in Venezuela.TT was associated with substantial,
      but heterogeneous reductions on parasite-related outcomes such as positive
      serology (9 studies, OR 0.21, 95% CI 0.10 to 0.44, I(2) = 76%), positive PCR (2
      studies, OR 0.50, 95% CI 0.27 to 0.92, I(2) = 0%), positive xenodiagnosis after
      treatment (6 studies, OR 0.35, 95% CI 0.14 to 0.86, I(2) = 79%), or reduction on
      antibody titres (3 studies, SMD -0.56, 95% CI -0.89 to -0.23, I(2) = 28%).
      Efficacy data on patient-related outcomes was largely from non-RCTs. TT with
      nitroderivatives was associated with potentially important, but imprecise and
      inconsistent reductions in progression of CCC (4 studies, 106 events, OR 0.74,
      95% CI 0.32 to 1.73, I(2) = 66%) and mortality after TT (6 studies, 99 events, OR
      0.55, 95% CI 0.26 to 1.14, I(2) = 48%). The overall median incidence of any
      severe side effects among 1475 individuals from five studies exposed to TT was
      2.7%, and the overall discontinuation of this two-month therapy in RCTs (5
      studies, 134 events) was 20.5% (versus 4.3% among controls) and 10.4% in other
      five studies (125 events). AUTHORS' CONCLUSIONS: Despite the evidence that TT
      reduced parasite-related outcomes, the low quality and inconsistency of the data
      for patient-important outcomes must be treated with caution. More geographically
      diverse RCTs testing newer forms of TT are warranted in order to 1. estimate
      efficacy more precisely, 2. explore factors potentially responsible for the
      heterogeneity of results and 3. increase knowledge on the efficacy/tolerance
      balance of conventional TT.

PMID- 24867877
TI  - The efficacy and safety of a chest pain protocol for short stay unit patients: A
      one year follow-up.
AB  - BACKGROUND: The Alfred Emergency Short Stay Unit initiated a chest pain protocol
      for patients presenting with chest pain to risk stratify for acute coronary
      syndrome (ACS). A 30-day follow-up of patients discharged with low-or
      intermediate risk of ACS demonstrated no deaths or ACS. AIMS: The purpose of this
      study was to evaluate the long-term safety of the chest pain protocol, a one year
      follow-up was undertaken. METHODS: A questionnaire was designed for the one-year
      follow-up and it was administered via a telephone interview by emergency nurses
      to document adverse cardiac events and health care utilisation. RESULTS: From 297
      patients, 224 (75%) were contacted 12 months following discharge. There was one
      death from stroke (0.4%; 95% confidence interval (CI): 0.01-2.5%) and another
      from an unknown cause. Five patients had been diagnosed with atrial fibrillation
      (2.2%; 95% CI: 0.7-5.1%), two patients had an acute myocardial infarction (0.9%;
      95% CI: 0.03-2.1%) and four were diagnosed with angina (1.8%; 95% CI: 0.9-3.2%).
      Nearly half (n=103, 46%; 95% CI: 39.5-52.5%) had returned to the emergency
      department (ED) for various conditions including 42 patients with further chest
      pain. Ninety-six patients (43%; 95% CI: 39.3-52.7%) had specialist referrals and
      124 investigations were performed. Thirty-four patients had cardiology referrals
      (15%; 95% CI: 10.7-20.5%) and 25 patients had gastroenterology referrals (11%;
      95% CI: 7.3-16.0%). Diagnostic cardiac tests were performed on 38 patients:
      coronary angiography (n=10), 24-hour Holter monitoring (n=17), 24-hour blood
      pressure (BP) monitoring (n=4), thallium scans (n=5), exercise stress test (n=1)
      and CT scan (n=1). CONCLUSION: Patients had a low risk of adverse events 12
      months after discharge but substantial continuing health care utilization was
      observed. Complete assessment by health care professionals prior to discharge may
      help mitigate representations.

PMID- 24867878
TI  - Sleep disturbance, symptoms, psychological distress, and health-related quality
      of life in pulmonary arterial hypertension.
AB  - BACKGROUND: Pulmonary arterial hypertension (PAH) is a devastating disease
      characterized by elevated pulmonary pressures that lead to right heart failure
      and premature mortality. Patients experience multiple symptoms including dyspnea,
      fatigue and chest pain, but little is known about sleep disturbance, PAH
      symptoms, psychological distress and health-related quality of life (HRQOL) in
      PAH. AIM: The purpose of this study was to describe the occurrence of sleep
      disturbance and compare PAH symptoms, psychological distress, and HRQOL across
      severity of sleep disturbance. METHODS: One hundred and ninety-one participants
      completed a socio-demographic and clinical data form, PAH Symptom Severity Scale,
      Profile of Mood States (POMS) short form and the Medical Outcomes Short Form-36
      (SF-36). Descriptive statistics were used to describe sleep disturbances;
      analysis of variance models were used to quantify differences in PAH symptoms,
      psychological distress and HRQOL by sleep disturbance groups. RESULTS: The
      majority of participants (n=162, 85%) were women with a mean age of 53 years.
      Sixty-five (34%) reported no sleep disturbance; 54 (28%) mild sleep disturbance;
      41 (22%) moderate sleep disturbance; and 31 (16%) severe sleep disturbance. Those
      reporting higher sleep disturbance severity reported worse PAH symptoms,
      psychological distress, and HRQOL. CONCLUSIONS: Sleep disturbance is a
      significant finding in PAH. Increasing levels of sleep disturbance are associated
      with worse PAH symptoms, psychological states, and health-related quality of
      life. Interventions that decrease sleep disturbances may improve symptoms and
      HRQOL.

PMID- 24867879
TI  - A novel molecular diagnostic marker for familial and early-onset coronary artery
      disease and myocardial infarction in the LRP8 gene.
AB  - BACKGROUND: Many single-nucleotide polymorphisms have been associated with
      coronary artery disease (CAD)/myocardial infarction (MI) by genome-wide
      association studies, but the diagnostic value of these variants is limited.
      Functional single-nucleotide polymorphism R952Q in LRP8 is associated with
      familial and early-onset CAD/MI. The objective of this study is to test whether
      fine mapping and haplotype analysis for single-nucleotide polymorphisms flanking
      R952Q may identify a haplotype that may serve as a molecular diagnostic marker
      for familial and early-onset CAD/MI. METHODS AND RESULTS: Five single-nucleotide
      polymorphisms (rs7546246, rs2297660, rs3737983, R952Q, and rs5177) were genotyped
      and analyzed in GeneQuest (381 patients with familial, early-onset CAD and 183
      patients with MI versus 560 controls) and the Italian population (248 patients
      with familial MI versus 308 controls). One novel risk haplotype, TACGC, was found
      only in patients with CAD and MI but not in controls. It was significantly
      associated with CAD (P=7.4*10(-7)) and MI (P=2.2*10(-9)) in GeneQuest. The
      finding was replicated in the Italian cohort (P=0.041). Sib-transmission
      disequilibrium test analysis showed a significant association between haplotype
      TACGC and CAD in GeneQuest II (P=0.039). Haplotype TACGC was not present in a
      South Korean population of 611 patients with CAD and 294 normal controls.
      TACGC/TACGC homozygotes tended to develop CAD/MI earlier and showed higher low
      density lipoprotein cholesterol levels than heterozygotes (P<0.05). CONCLUSIONS:
      The rare haplotype TACGC in LRP8 confers a significant risk of familial, early
      onset CAD/MI. Because the risk haplotype exists only in patients with familial
      and early-onset CAD/MI, we propose that it may be a molecular diagnostic marker
      for diagnosis of familial, early-onset CAD/MI in some white populations.

PMID- 24867880
TI  - Smokers still underestimate the risks posed by secondhand smoke: a repeated cross
      sectional study.
AB  - BACKGROUND: Little is known about risk perception of secondhand smoke (SHS) and
      its changes over time. The aim of the study was to examine the role of smoking
      status and demographics on perceiving a range of health risks of SHS exposure and
      their trends over time among a representative sample of the Irish general
      population. METHODS: This study included 2 repeated cross-sectional samples of
      Irish adults in 1999 (n = 1,240) and 2006 (n = 1,000), in addition to a
      representative sample of General Practitioners (2006: n = 248), sampled as a
      health care professional's view on SHS risk. Participants were asked to consider
      whether a nonsmoker, exposed to SHS, is at an increased risk of asthma, lung
      cancer, heart disease, bronchitis, diabetes, and ear infections in children.
      RESULTS: There was a significant increase in the general population's risk
      perception of SHS for asthma, lung cancer, heart disease, and bronchitis from
      1999 to 2006. Not even half of the general population in 1999 and in 2006
      perceived a risk for the development of ear infections in children with SHS
      exposure (45% in 1999, 46% in 2006). With the exception of ear infections in
      children in 2006, the risk perception of all diseases differed significantly by
      smoking status; smokers' risk perception of SHS was significantly lower.
      Encouraging results suggest that the differences in risk perception between
      smokers and nonsmokers have decreased. CONCLUSION: Risk perception of SHS
      exposure has improved as has the gap in perception between smokers and
      nonsmokers. This research points to a lack of awareness among the general
      population of the risk perception of SHS exposure to children.

PMID- 24867882
TI  - Combinatorial MAPLE gradient thin film assemblies signalling to human
      osteoblasts.
AB  - There is increased interest in smart bioactive materials to control tissue
      regeneration for the engineering of cell instructive scaffolds. We introduced
      combinatorial matrix-assisted pulsed laser evaporation (C-MAPLE) as a new method
      for the fabrication of organic thin films with a compositional gradient.
      Synchronized C-MAPLE of levan and oxidized levan was employed to assemble a two
      compound biopolymer film structure. The gradient of the film composition was
      validated by fluorescence microscopy. In this study, we investigated the cell
      response induced by the compositional gradient using imaging of early osteoblast
      attachment and analysis of signalling phosphoprotein expression. Cells attached
      along the gradient in direct proportion to oxidized levan concentration. During
      this process distinct areas of the binary gradient have been shown to modulate
      the osteoblasts' extracellular signal-regulated kinase signalling with different
      propensity. The proposed fabrication method results in the preparation of a new
      bioactive material, which could control the cell signalling response. This
      approach can be extended to screen new bioactive interfaces for tissue
      regeneration. 

PMID- 24867881
TI  - RARRES3 suppresses breast cancer lung metastasis by regulating adhesion and
      differentiation.
AB  - In estrogen receptor-negative breast cancer patients, metastatic relapse usually
      occurs in the lung and is responsible for the fatal outcome of the disease. Thus,
      a better understanding of the biology of metastasis is needed. In particular,
      biomarkers to identify patients that are at risk of lung metastasis could open
      the avenue for new therapeutic opportunities. Here we characterize the biological
      activity of RARRES3, a new metastasis suppressor gene whose reduced expression in
      the primary breast tumors identifies a subgroup of patients more likely to
      develop lung metastasis. We show that RARRES3 downregulation engages metastasis
      initiating capabilities by facilitating adhesion of the tumor cells to the lung
      parenchyma. In addition, impaired tumor cell differentiation due to the loss of
      RARRES3 phospholipase A1/A2 activity also contributes to lung metastasis. Our
      results establish RARRES3 downregulation as a potential biomarker to identify
      patients at high risk of lung metastasis who might benefit from a differentiation
      treatment in the adjuvant programme. 

PMID- 24867884
TI  - Ischemic burden by 3-dimensional myocardial perfusion cardiovascular magnetic
      resonance: comparison with myocardial perfusion scintigraphy.
AB  - BACKGROUND: The extent and severity of ischemia on myocardial perfusion
      scintigraphy (MPS) is commonly used to risk-stratify patients with coronary
      artery disease. Estimation of ischemic burden by cardiovascular magnetic
      resonance (CMR) with conventional 2-dimensional myocardial perfusion methods is
      limited by incomplete cardiac coverage. More recently developed 3-dimensional
      (3D) myocardial perfusion CMR, however, provides whole-heart coverage. The aim of
      this study was to compare ischemic burden on 3D myocardial perfusion CMR with
      (99m)Tc-tetrofosmin MPS. METHODS AND RESULTS: Forty-five patients who had
      undergone clinically indicated MPS underwent rest and adenosine stress 3D
      myocardial perfusion and late gadolinium enhancement CMR. Summed stress and rest
      scores were calculated for MPS and CMR using a 17-segment model and expressed as
      a percentage of the maximal possible score. Ischemic burden was defined as the
      difference between stress and rest scores. 3D myocardial perfusion CMR and MPS
      agreed in 38 of the 45 patients for the detection of any inducible ischemia. The
      mean ischemic burden for MPS and CMR was similar (7.5+/-8.9% versus 6.8+/-9.5%,
      respectively, P=0.82) with a strong correlation between techniques (rs=0.70,
      P<0.001). In a subset of 33 patients who underwent clinically indicated invasive
      coronary angiography, sensitivities and specificities of the 2 techniques to
      detect angiographic coronary artery disease were similar (McNemar P=0.45).
      CONCLUSIONS: 3D myocardial perfusion CMR is an alternative to MPS for detecting
      the presence and rating the severity of ischemia.

PMID- 24867883
TI  - Coatings and surface modifications imparting antimicrobial activity to orthopedic
      implants.
AB  - Bacterial colonization and biofilm formation on an orthopedic implant surface is
      one of the worst possible outcomes of orthopedic intervention in terms of both
      patient prognosis and healthcare costs. Making the problem even more vexing is
      the fact that infections are often caused by events beyond the control of the
      operating surgeon and may manifest weeks to months after the initial surgery.
      Herein, we review the costs and consequences of implant infection as well as the
      methods of prevention and management. In particular, we focus on coatings and
      other forms of implant surface modification in a manner that imparts some
      antimicrobial benefit to the implant device. Such coatings can be classified
      generally based on their mode of action: surface adhesion prevention,
      bactericidal, antimicrobial-eluting, osseointegration promotion, and combinations
      of the above. Despite several advances in the efficacy of these antimicrobial
      methods, a remaining major challenge is ensuring retention of the antimicrobial
      activity over a period of months to years postoperation, an issue that has so far
      been inadequately addressed. Finally, we provide an overview of additional
      figures of merit that will determine whether a given antimicrobial surface
      modification warrants adoption for clinical use.

PMID- 24867886
TI  - Factor Structure of the Spiritual Well-Being Scale: Cross-Cultural Comparisons
      Between Jordanian Arab and Malaysian Muslim University Students in Jordan.
AB  - This study reported the differences in factor structure of the Spiritual Well
      Being Scale (SWBS) among Jordanian Arab and Malaysian Muslim participants and
      further examined its validity and reliability. A convenience sample of 553
      Jordanian Arab and 183 Malaysian Malay Muslim university students was recruited
      from governmental universities in northern Jordan. The findings of this study
      revealed that this scale consists of two factors for the Jordanian Arab group,
      representing the "Religious Well-Being" and the "Existential Well-Being"
      subscales, and consists of three factors for the Malaysian group, representing
      the "Affiliation/Meaning and Purpose," "Positive Existential Well-Being/God
      Caring and Love," and "Alienation/Despair" subscales. In conclusion, the factor
      structure of the SWBS for both groups in this study was psychometrically sound
      with evidence of acceptable to good validity and reliability. Furthermore, this
      study supported the multidimensional nature of the SWBS and the earlier notion
      that ethnicity shapes responses to this scale. 

PMID- 24867887
TI  - Antheraea pernyi silk fibroin for targeted gene delivery of VEGF165-Ang-1 with
      PEI.
AB  - Vascularization is a crucial challenge in tissue engineering. One solution for
      this problem is to implant scaffolds that contain functional genes that promote
      vascularization by providing angiogenic growth factors via a gene delivery
      carrier. Poly(ethylenimine) (PEI) is a gene delivery carrier with high
      transfection efficiency but with cytotoxicity. To solve this problem, we utilized
      Antheraea pernyi silk fibroin (ASF), which has favorable cytocompatibility and
      biodegradability, RGD sequences and a negative charge, in conjunction with PEI,
      as the delivery vector for vascular endothelial growth factor (VEGF) 165
      angiopoietin-1 (Ang-1) dual gene simultaneous expression plasmid, creating an
      ASF/PEI/pDNA complex. The results suggested that the zeta potential of the
      ASF/PEI/pDNA complex was significantly lower than that of the PEI/pDNA complex.
      Decreased nitrogen and increased oxygen on the surface of the complex
      demonstrated that the ASF had successfully combined with the surface of the
      PEI/pDNA. Furthermore, the complexes resisted digestion by nucleic acid enzymes
      and degradation by serum. L929 cells were cultured and transfected in vitro and
      improved cytotoxicity was found when the cells were transfected with ASF/PEI/pDNA
      compared with PEI/pDNA. In addition, the transfection efficiency and VEGF
      secretion increased. In general, this study provides a novel method for
      decreasing the cytotoxicity of PEI gene delivery vectors and increasing
      transfection efficiency of angiogenesis-related genes. 

PMID- 24867888
TI  - Biochemical characterization of photosystem I-associated light-harvesting
      complexes I and II isolated from state 2 cells of Chlamydomonas reinhardtii.
AB  - Two photosystems, PSI and PSII, drive electron transfer in series for oxygenic
      photosynthesis using light energy. To balance the activity of the two
      photosystems under varying light conditions, mobile antenna complexes, light
      harvesting complex IIs (LHCIIs), shuttle between the two photosystems during
      state transitions. PSI forms a complex consisting of PSI core and its peripheral
      light-harvesting complex (LHCI) in plants and algae. In a previous study, we
      isolated a PSI-LHCI-LHCII supercomplex containing both LHCI and LHCII from state
      2 cells of Chlamydomonas reinhardtii. In the present study, we isolated a PSI
      LHCI-LHCII supercomplex associating with more LHCII complexes under a further
      optimized protocol. We determined its antenna size by three independent methods
      and revealed that the associated LHCIIs increased the antenna size by about 70
      Chls and transferred light energy to the PSI core. Uniform labeling of total
      cellular proteins with (14)C indicated that the PSI-LHCI-LHCII supercomplex
      contains 1.85 copies of LhcbM5 and CP29 and 1.29 copies of CP26. PSI-LHCI-LHCII
      also stably bound 0.4 copy of ferredoxin-NADP(+) oxidoreductase (FNR) that
      catalyzes light-induced electron transfer from PSI to NADP(+) in the presence of
      ferredoxin. We discuss the possible organization of these LHCIIs in the PSI-LHCI
      LHCII supercomplex. 

PMID- 24867890
TI  - Pharmacology and signaling of MAS-related G protein-coupled receptors.
AB  - Signaling by heptahelical G protein-coupled receptors (GPCR) regulates many vital
      body functions. Consequently, dysfunction of GPCR signaling leads to pathologic
      states, and approximately 30% of all modern clinical drugs target GPCR. One
      decade ago, an entire new GPCR family was discovered, which was recently named
      MAS-related G protein-coupled receptors (MRGPR) by the HUGO Gene Nomenclature
      Committee. The MRGPR family consists of ~40 members that are grouped into nine
      distinct subfamilies (MRGPRA to -H and -X) and are predominantly expressed in
      primary sensory neurons and mast cells. All members are formally still considered
      "orphan" by the Committee on Receptor Nomenclature and Drug Classification of the
      International Union of Basic and Clinical Pharmacology. However, several distinct
      peptides and amino acids are discussed as potential ligands, including beta
      alanine, angiotensin-(1-7), alamandine, GABA, cortistatin-14, and cleavage
      products of proenkephalin, pro-opiomelanocortin, prodynorphin, or proneuropeptide
      FF-A. The full spectrum of biologic roles of all MRGPR is still ill-defined, but
      there is evidence pointing to a role of distinct MRGPR subtypes in nociception,
      pruritus, sleep, cell proliferation, circulation, and mast cell degranulation.
      This review article summarizes findings published in the last 10 years on the
      phylogenetic relationships, pharmacology, signaling, physiology, and agonist
      promoted regulation of all MRGPR subfamilies. Furthermore, we highlight
      interactions between MRGPR and other hormonal systems, paying particular
      attention to receptor multimerization and morphine tolerance. Finally, we discuss
      the challenges the field faces presently and emphasize future directions of
      research. 

PMID- 24867889
TI  - sAPP modulates iron efflux from brain microvascular endothelial cells by
      stabilizing the ferrous iron exporter ferroportin.
AB  - A sequence within the E2 domain of soluble amyloid precursor protein (sAPP)
      stimulates iron efflux. This activity has been attributed to a ferroxidase
      activity suggested for this motif. We demonstrate that the stimulation of efflux
      supported by this peptide and by sAPPalpha is due to their stabilization of the
      ferrous iron exporter, ferroportin (Fpn), in the plasma membrane of human brain
      microvascular endothelial cells (hBMVEC). The peptide does not bind ferric iron
      explaining why it does not and thermodynamically cannot promote ferrous iron
      autoxidation. This peptide specifically pulls Fpn down from the plasma membrane
      of hBMVEC; based on these results, FTP, for ferroportin-targeting peptide,
      correctly identifies the function of this peptide. The data suggest that in
      stabilizing Fpn via the targeting due to the FTP sequence, sAPP will increase the
      flux of iron into the cerebral interstitium. This inference correlates with the
      observation of significant iron deposition in the amyloid plaques characteristic
      of Alzheimer's disease. 

PMID- 24867891
TI  - Optimization in stent implantation by manual thrombus aspiration in ST-segment
      elevation myocardial infarction: findings from the EXAMINATION trial.
AB  - BACKGROUND: Manual thrombus aspiration (TA) is effective to reduce the thrombus
      burden during primary percutaneous coronary intervention for ST-elevation
      myocardial infarction. The objective of this study is to assess the impact of
      manual TA on stent implantation during primary percutaneous coronary
      intervention. METHODS AND RESULTS: Population of the EXAMINATION trial (n=1498)
      was divided into 2 groups according to the use of TA. Immediate angiographic
      results, primary patient-oriented end point (combination of all-cause death,
      myocardial infarction, and any revascularization) and secondary device-oriented
      end point (combination of cardiac death, target vessel myocardial infarction, and
      clinically driven target lesion revascularization), definite/probable stent
      thrombosis, and major/minor bleeding were evaluated at 2 years. A total of 976
      (65.2%) patients were classified into TA group and 522 (34.8%) patients into
      nonthrombus aspiration group. Manual TA was most frequently used in patients with
      worse initial thrombolysis in myocardial infarction flow. The TA group received
      less number of stents implanted (1.35 +/- 0.62 versus 1.45 +/- 0.71, P = 0.005)
      with bigger size (3.25 +/- 0.44 versus 3.11 +/- 0.46 mm, P < 0.001) compared with
      the nonthrombus aspiration group. A higher rate of direct stenting (69.2% versus
      43.3%, P < 0.001) with lower rate of postdilatation (13.0% versus 18.0%, P <
      0.009) was also present in the TA group compared with the nonthrombus aspiration
      group. At 2-year follow-up, no differences in clinical end point were observed
      between groups. CONCLUSIONS: Manual TA during primary percutaneous coronary
      intervention is associated with a higher rate of direct stenting, a lower rate of
      postdilatation, and larger and less stents in comparison with conventional
      primary percutaneous coronary intervention. Conversely, manual TA had no apparent
      impact on clinical outcomes at long-term follow-up. CLINICAL TRIAL REGISTRATION:
      http://www.clinicaltrials.gov. Unique identifier: NCT00828087.

PMID- 24867892
TI  - Use and performance of the Melody Transcatheter Pulmonary Valve in native and
      postsurgical, nonconduit right ventricular outflow tracts.
AB  - BACKGROUND: Melody Transcatheter Pulmonary Valve (TPV) replacement therapy
      represents an important advance in congenital cardiovascular interventions. The
      off-label extension of the Melody TPV to patients with nonconduit outflow tracts
      (right ventricular outflow tract [RVOT]) has the potential to vastly expand the
      population of patients eligible to benefit from nonsurgical restoration of RVOT
      function. However, knowledge on the performance of the Melody TPV in this setting
      is limited. METHODS AND RESULTS: This is a multicenter, retrospective review of
      the Melody TPV when placed in nonconduit RVOTs, in which at least a portion of
      the circumference was composed of native tissue. Five centers contributed data on
      31 patients. The median age at implantation was 24 years (range, 7-66). At a
      median follow-up of 15 months, all patients were alive. No patient had greater
      than mild TPV insufficiency, and the median maximum instantaneous gradients
      across the RVOT was 23 mm Hg. Stent fracture occurred in 32%. Eight patients
      developed more than mild TPV obstruction, of whom 6 were associated with
      identified stent fracture. Three patients developed blood stream infections.
      There were 5 reinterventions in 3 patients, including 3 repeat TPV implantations
      and 2 TPV explantations. CONCLUSIONS: Melody TPV implantation is feasible in
      selected patients with RVOTs comprised solely or predominantly native tissue and
      has the potential to expand the population of patients eligible to benefit from
      nonsurgical restoration of RVOT function. In early follow-up, valve competency
      seems preserved. The dominant mechanism of valve dysfunction seems to be related
      to stent fracture with recurrent obstruction. Additional data are necessary to
      better understand how to safely expand TPV therapy to this population.

PMID- 24867893
TI  - Comparison between massage and routine physical therapy in women with sub acute
      and chronic nonspecific low back pain.
AB  - OBJECTIVE: The aim of this study was to investigate the comparison of massage
      therapy and routine physical therapy on patients with sub acute and chronic
      nonspecific low back pain. METHODS AND MATERIALS: Thirty volunteer female
      subjects with a sub acute or chronic nonspecific low back pain were randomly
      enrolled in two groups, massage therapy and routine physical therapy. After
      massage application, the hamstring and paravertebral muscles stretching and also
      stabilizing exercises were prescribed. In the routine physical therapy group,
      TENS, US and vibrator were used besides exercises. Pain intensity according to
      Numerical Rating Scale, functional disability level in accordance to Oswestry
      Disability Index, and modified Schober test, for measurement of flexion range of
      motion, before and after ten sessions of treatment were used to evaluate the
      effectiveness of the treatment. RESULTS: Pain intensity, Oswestry Disability
      Index and flexion range of motion had shown significant differences before and
      after intervention in both groups (p<0.001). The statistical analysis revealed
      that the massage therapy had significantly improved the pain intensity and
      Oswestry Disability Index compared to routine physical therapy (p=0.015, p=0.013
      respectively), but the range of motion changes were not significant between two
      groups (p=1.00). CONCLUSION: It can be concluded that both massage therapy and
      routine physical therapy are useful for sub acute and chronic nonspecific low
      back pain treatment especially if accompanied with exercise. However, massage is
      more effective than other electrotherapy modalities, and it can be used alone or
      with electrotherapy for the treatment of patients with low back pain.

PMID- 24867894
TI  - Maximum expiration activates the abdominal muscles during side bridge exercise.
AB  - BACKGROUND: Recent studies have indicated that maximum expiration could be a
      useful way of performing challenging exercises that include coactivation of the
      deep and superficial abdominal muscles. However, little is known about the effect
      of maximum expiration on the activity of the abdominal muscles during lumbar
      stabilizing exercise. OBJECTIVES: The purpose of our study was to quantify
      changes in the activities of the abdominal muscles during side bridge exercise in
      combination with maximum expiration. DESIGN: Experimental laboratory study.
      METHODS: The activities of the rectus abdominis (RA), external oblique (EO), and
      internal oblique (IO) muscles were measured using electromyography in 12 healthy
      men performing 3 tasks: holding the breath after maximum expiration in the prone
      position, holding the breath after resting expiration during side bridge
      exercise, and holding the breath after maximum expiration during side bridge
      exercise. RESULTS: Significant increases in the activities of the abdominal
      muscles (RA, EO, and IO) occurred with maximum expiration when compared with
      resting expiration during side bridge exercise (P < 0.05). CONCLUSION: This is
      the first study to demonstrate the effect of maximum expiration on abdominal
      muscle activities during a stabilizing exercise, thus contributing to existing
      knowledge about therapeutic exercise for alternative core training.

PMID- 24867895
TI  - Botulinum toxin type A and myofascial pain syndrome: a retrospective study of 301
      patients.
AB  - BACKGROUND: Botulinum toxin type A (BTX-A) intramuscular injections have been
      used for the treatment of myofascial pain syndrome (MPS), although its efficacy
      remains still unknown and its safety is controversial. OBJECTIVE: To analyze the
      effectiveness and safety of the injection protocol for BTX-A in the shoulder
      scapular and lumbar-pelvic girdles combined with physiotherapy in patients with
      primary and secondary MPS. METHODS: Retrospective descriptive study including 301
      medical files of patients with persistent MPS. Positive responses to treatment
      were considered to be a satisfactory level of effectiveness with 50% pain relief
      or a fully satisfactory level of effectiveness at 80%. RESULTS: Overall, 58.1% of
      patients obtained a positive result at 6 months. Differences in effectiveness
      were found between primary MPS (82.9% of patients) and secondary MPS (54.9%;
      p=0.002). In patients with secondary MPS, differences in effectiveness arose
      based on pathologies associated with MPS (p=0.03). In 23.9% of cases, mild and
      temporary adverse effects were observed post-infiltration. CONCLUSIONS: BTX-A
      injections and physiotherapy is an alternative to conventional treatment which
      should be considered when treating refractory MPS. Nonetheless, the differences
      in effectiveness based on diagnosis suggest the need to clarify the criteria used
      to select patients with MPS in future clinical trials and applications.

PMID- 24867896
TI  - Relationship between neck disability and mandibular range of motion.
AB  - BACKGROUND AND OBJECTIVE: There is a close interaction between the mandibular and
      cervical systems due to the existing neurological and biomechanical
      communications. This study aimed to evaluate the relationship between neck
      disability and mandibular range of motion (ROM). MATERIALS AND METHODS: Fifty-two
      women aged between 18 and 40 years were recruited and allocated to four groups
      using two outcome measures: the Neck Disability Index (NDI) and the Research
      Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD): Group I (n=13),
      healthy volunteers; Group II (n=13), volunteers with TMD and neck disability;
      Group III (n=13), volunteers with TMD and without neck disability; and Group IV
      (n=13), volunteers with neck disability and without TMD. Mandibular ROM was
      evaluated as part of the RDC/TMD clinical examination. Statistical analysis
      involved one-way ANOVA followed by Tukey's test for comparisons between groups.
      Spearman's correlation coefficients were calculated to determined correlations
      among the variables. RESULTS: Significant differences were found in the
      mandibular ROM of functional opening in the comparisons between Groups I and III
      (p=0.009) and between Groups III and IV (p=0.024). No significant association was
      found between mandibular ROM and the NDI score (p > 0.05). CONCLUSION: Based on
      the methodology employed, there is no association between mandibular ROM and neck
      disability in university women. In this sense, clinical interventions focusing on
      the flexibility of the temporomandibular joint does not have repercussions on the
      neck disability and vice versa.

PMID- 24867897
TI  - The role of the descending inhibitory pain mechanism in musculoskeletal pain
      following high-velocity, low amplitude thrust manipulation: a review of the
      literature.
AB  - BACKGROUND: Although the antinociceptive effect of high-velocity, low amplitude
      thrust manipulation (HVLAM) has been recognized by numerous systematic reviews,
      the underlying mechanism for manipulation-related pain relief remains poorly
      understood. An increasing number of studies have explored its analgesic mechanism
      suggesting that the excitation of the descending inhibitory pain mechanism (DIPM)
      might play the most important role for musculoskeletal pain relief. OBJECTIVE:
      The objective of this review is to investigate the role of the DIPM in
      musculoskeletal pain following HVLAM as well as to identify the pain-relieving
      importance of this technique within clinical practice. METHODOLOGY: English
      literature databases were searched to find studies related to the objective of
      the present review. RESULTS AND CONCLUSIONS: Findings from current literature
      support that HVLAM has a profound influence on nociceptive stimulus via the
      possible activation of the DIPM. It seems that the application of this technique
      activates the periaqueductal gray region area of the midbrain, stimulates the
      noradrenergic descending system and at the level of the spinal cord, the
      nociceptive afferent barrage is reduced and mechanical hypoalgesia is induced.
      However, the literature on HVLAM induced-analgesia is still problematic regarding
      the methodological design of the existing research. Despite these limitations,
      the clinical importance of the activation of the DIPM should not be ignored since
      the resulted analgesic effect of this technique can provide a window of
      opportunity to restore impaired physical performance and disability.

PMID- 24867898
TI  - Single level anterior interbody fusion and fixation in the treatment of
      thoracolumbar fractures.
AB  - BACKGROUND: Many surgical methods are available for repairing thoracolumbar
      fractures including short-segment internal fixation with posterior pedicle screws
      and anterior decompression and reduction. However, most methods are associated
      with significant surgical trauma and long postoperative recovery. The purpose of
      this study was to describe anterior single level interbody fusion and fixation
      for the repair of thoracolumbar fractures which may reduce surgical trauma and
      help speed recovery. METHODS: A group of 21 patients who underwent single level
      anterior interbody fusion and fixation from June 2006 to June 2011 were compared
      with a group of 21 patients who underwent double level anterior interbody fusion
      and fixation during the same period. The groups were compared with regard to
      operation time, intraoperative blood loss, fracture healing time, ratio of pre-
      to postoperative endplate height between adjacent vertebrae, Cobb angle in the
      sagittal plane, recovery of neural function, and internal fusion failure.
      RESULTS: The 2 groups were similar with the exception of fracture location
      (P=0.017). The patients who underwent the single level procedure had a shorter
      operation time (P < 0.001), less blood loss (P < 0.001), and shorter follow-up (P
      < 0.001). Both groups had significant improvement in Cobb angle at 1 week and 1
      year after surgery, but there was no significant difference between the groups.
      Both groups also exhibited improvement in neurological function, and the
      difference in improvement between the groups was not significant. CONCLUSIONS:
      Single level intervertebral fusion and internal fixation for thoracolumbar
      fractures provides as satisfactory an outcome as the traditional approach, double
      level anterior interbody fusion and fixation, and reduces the degree of surgical
      trauma.

PMID- 24867899
TI  - Comparison of quality of life in low back pain patients and healthy subjects by
      using WHOQOL-BREF.
AB  - BACKGROUND AND OBJECTIVES: Low back pain and consequence disability is one of the
      most prevalence musculoskeletal disorders that human being ever had involved.
      Quality of life is a multidimensional concept and is beyond absolute physical
      health. In this study, we compared QOL between low back pain patients and healthy
      people using WHOQOL-BREF which is a generic and overall instrument. METHODS: This
      descriptive-analytic study was carried out on 256 low back pain patients and
      healthy people in Shahid Beheshti Hospital, Babol. They filled out the
      questionnaires personally and the scores of different domains in two groups were
      compared. WHOQOL-BREF has four domains of physical health, psychological health,
      social relations and environment health. The range of scores in each of these
      domains is from 4-20. The two questions are about the general quality of life and
      general health. Overall, a higher score indicates better quality of life.
      RESULTS: The participants' age range was from 18 to 63 with the mean +/- SD of
      36.63 +/- 10.99. The scores of these four domains and general quality of life and
      general health of WHOQOL-BREF were lower in low back pain patients. These
      differences were statistically significant in physical health and environmental
      health. CONCLUSIONS: Lower QOL in low back pain patients necessitate doing some
      interventions such as education and rehabilitation in this group. This indicates
      the importance of more attention to these patients to plan future treatments in
      order to reinforce these domains.

PMID- 24867900
TI  - Association between bone scintigraphy    features of spinal degeneration and  
      anthropometric and demographic variables.
AB  - BACKGROUND AND OBJECTIVES: Bone scintigraphy is a molecular imaging technique
      routinely used for the evaluation of benign and malignant bone abnormalities.
      This study aimed at evaluating spinal degenerative changes detected by bone
      scintigraphy and determining associations between image features and patients'
      anthropometric and demographic variables. MATERIAL AND METHOD: In a cross
      sectional study, 64 men and 52 women underwent bone scintigraphy. Experts
      identified all image regions suggesting degenerative joint disease (DJD) and
      classified region intensity on a 3-point scale. Image characteristics were
      correlated to the patients' body mass index (BMI), age, weight, height, activity
      level, and sex. Data analysis included descriptive statistics and association
      coefficients. RESULTS: DJD was found in 53 patients (46%). In men, there was weak
      but statistically significant correlation between DJD and activity level, and DJD
      and age, but not BMI or weight. In women, only a weak, not statistically
      significant, linear correlation was found between DJD and BMI, and DJD and
      weight. CONCLUSION: Molecular imaging with bone scintigraphy showed that spinal
      degenerations are associated with different anthropometric and demographic
      features in men and women. Interestingly, no association was found between DJD
      and increased body weight in men while a weak association may exist in women. The
      results prompt for additional studies to better determine the risk factors for
      DJD and low back pain in male and female patients. LEVEL OF EVIDENCE: Diagnostic
      study, Level II (retrospective study).

PMID- 24867901
TI  - Anteroposterior curvatures of the spine in adolescent athletes.
AB  - OBJECTIVE: To assess the shape of anteroposterior vertebral curvatures in
      adolescents who practice team sports. MATERIAL AND METHODS: 57 females and 104
      males aged 14-17 years, playing volleyball, basketball or handball, and 63
      females and 99 males as a control group. A Rippstein plurimeter was used to
      measure the angles of thoracic kyphosis and lumbar lordosis. RESULTS: The study
      has revealed significant differences in lumbar lordosis in male athletes compared
      to the control (p=0.01). Male volleyball players had greater thoracic kyphosis
      (p=0.002) than basketball players. Female athletes had lower thoracic kyphosis
      than the control group (p < 0.01). Normal values of thoracic kyphosis were more
      frequent in female athletes and male handball players whereas normal lumbar
      lordosis was more frequently seen in female volleyball players and male control
      group. Our investigations revealed significant (p < 0.05) correlations between
      the anteroposterior curvature of the spine and somatic parameters. CONCLUSION:
      Differences in thoracic kyphosis or lumbar lordosis among the athletes and the
      control group might be due to postural muscles strengthening as a result of
      regular engagement in intensive exercise. The variability of anteroposterior
      spine curvatures may not only be associated with directional physical activity;
      some contribution of the somatic structure is also possible.

PMID- 24867902
TI  - Normal postural responses preceding shoulder flexion: co-activation or asymmetric
      activation of transverse abdominis?
AB  - BACKGROUND AND OBJECTIVES: It is suggested that activation of the transverse
      abdominis muscle has a stabilizing effect on the lumbar spine by raising intra
      abdominal pressure without added disc compression. However, its feedforward
      activity has remained a controversial issue. In addition, research regarding
      bilateral activation of trunk muscles during a unilateral arm movement is
      limited. The aim of this study was to evaluate bilateral anticipatory activity of
      trunk muscles during unilateral arm flexion. MATERIALS AND METHODS: Eighteen
      healthy subjects (aged 25 +/- 3.96 years) participated in this study and
      performed 10 trials of rapid arm flexion in response to a visual stimulus. The
      electromyographic activity of the right anterior deltoid (AD) and bilateral trunk
      muscles including the transverse abdominis/internal oblique (TA/IO), superficial
      lumbar multifidus (SLM) and lumbar erector spine (LES) was recorded. The onset
      latency and anticipatory activity of the recorded trunk muscles were calculated.
      RESULTS: The first muscle activated in anticipation of the right arm flexion was
      the left TA/IO. The right TA/IO activated significantly later than all other
      trunk muscles (P < 0.0005). In addition, anticipatory activity of the right TA/IO
      was significantly lower than all other trunk muscles (P < 0.0005). There was no
      significant difference in either onset latency or anticipatory activity among
      other trunk muscles (P > 0.05). CONCLUSION: Healthy subjects showed no bilateral
      anticipatory co-activation of TA/IO in unilateral arm elevation. Further
      investigations are required to delineate normal muscle activation pattern in
      healthy subjects prior to prescribing bilateral activation training of transverse
      abdominis for subjects with chronic low back pain.

PMID- 24867903
TI  - Effectiveness of massage therapy as co-adjuvant treatment to exercise in
      osteoarthritis of the knee: a randomized control trial.
AB  - BACKGROUND: The effectiveness of exercise therapy in the treatment of
      osteoarthritis of the knee (KOA) is widely evidenced. The current study aims to
      compare the effectiveness of massage therapy as a co-adjuvant treatment for KOA.
      METHODS: A blind, randomized controlled trial design was used. Eighteen women
      were randomly allocated to two different groups. Group A was treated with massage
      therapy and an exercise program, and Group B was treated with the exercise
      program alone. The intervention lasted for 6 weeks. Outcomes were assessed using
      a verbal analogue scale (VAS), the WOMAC index, and the Get-Up and Go test.
      Baseline, post-treatment, and 1- and 3- month follow-up data were collected.
      Values were considered statistically significant at a p < 0.05. The Mann-Whitney
      U test was applied in order to find out the differences between groups, and to
      verify the existence of such differences, the Friedman Test for repeated measures
      complemented with multiple comparisons tests was carried out. RESULTS: In both
      groups, significant differences were found in the three variables between the
      baseline measurement and three months after treatment, with the exception of the
      WOMAC variable in group B (p=0.064) No significant differences were found between
      both groups in the WOMAC index (p=0.508) and VAS (p=0.964) variables and the Get
      Up and Go test (p=0.691). CONCLUSION: Combining exercise-based therapy with
      massage therapy may lead to clinical improvement in patients with KOA. The use of
      massage therapy combined with exercise as a treatment for gonarthrosis does not
      seem to have any beneficial effects.

PMID- 24867904
TI  - Upper trapezius relaxation induced by TENS   and interferential current in
      computer users   with chronic nonspecific neck discomfort:   An electromyographic
      analysis.
AB  - BACKGROUND: Recent studies have shown that a transcutaneous electrical nerve
      stimulation (TENS) and interferential current (IFC) application reduces pain in
      subjects with musculoskeletal disorders. However there are no clinical trials
      evaluating or comparing the muscle relaxation generated for these devices.
      PURPOSE: To compare the muscle relaxation of the upper trapezius induced by the
      application of TENS and IFC in females with chronic nonspecific neck discomfort.
      METHODS: Sixty-four females between 18 and 40 years of age and a history of
      nonspecific neck discomfort were randomly assigned to a TENS or an IFC group. The
      women in the TENS (N = 32; mean age 22 years) and IFC (N = 32, mean age 23 years)
      group were submitted to current application during 3 consecutive days and were
      assessed by electromyography (EMG) in different times aiming to quantify the
      muscular tension of the upper trapezius. A visual analogue scale (VAS) was used
      as pain measure at baseline (before TENS or IFC application) and at the end of
      the study. RESULTS: At baseline, demographic, pain, and EMG assessment data were
      similar between groups. Those in the IFC group had a significant trapezius
      relaxation after 3 IFC applications when compared to baseline and intermediate
      evaluations (P < 0.05). In contrast, the same analysis showed no significant
      difference between all assessments in the TENS group (P >0.05). In relation to
      pain relief, both groups showed an improvement at the end of the study when
      compared to baseline (both,P <0.05). The between-group analysis showed no
      difference for the subjects who received such IFC as TENS application (P <0.05).
      CONCLUSION: IFC induced the upper trapezius relaxation after 3 sessions in
      females with neck discomfort, but the TENS application did not change the
      muscular tension. However, these results should be carefully interpreted due to
      the lack of differences between groups. A significant pain decrease was found in
      the subjects of both groups, however, only the IFC application presented a
      clinically important improvement.

PMID- 24867905
TI  - Taping for plantar fasciitis.
AB  - BACKGROUND: Plantar fasciitis is considered the most common cause of foot pain.
      Numerous non-surgical treatments have been used to relieve symptoms. Taping is
      one of the most widespread treatments, with several techniques utilized in
      clinical practice. OBJECTIVE: To evaluate, based on existing literature, the
      efficacy of different taping techniques in relieving symptoms and dysfunction
      caused by plantar fasciitis. METHODS: PubMed, CINAHL, PEDro, ISIWeb of Science,
      and Google Scholar databases were searched from inception until December 2012,
      using a predefined search strategy. Controlled trials of any methodological
      quality were included, without any language restrictions. The methodological
      quality of interventional studies was evaluated inter alia by the PEDro score.
      RESULTS: Five randomized control trials, one cross-over study and two single
      group repeated measures studies met the inclusion criteria. Two studies were high
      quality; two were moderate quality and four were of poor methodological quality.
      All eight studies favored the use of different taping techniques. The most common
      technique was low dye taping. CONCLUSION: We found that in the short-term, taping
      is beneficial in treating plantar fasciitis. The best evidence exists for low dye
      taping and calcaneal taping. More research is needed to investigate long-term
      effect and effectiveness of specific taping techniques.

PMID- 24867906
TI  - How effective is a modified exercise program on its own or with back school in
      chronic low back pain? A randomized-controlled clinical trial.
AB  - BACKGROUND AND OBJECTIVES: The aim of this trial is to search effectiveness of
      specifically adapted exercise programs on its own and with low back school on
      pain, disability, trunk and quadriceps muscle strength, walking performance,
      spinal mobility, quality of life (QOL), and depression in the patients with
      chronic low back pain (CLBP). MATERIAL AND METHOD: A total of 121 patients with
      definite CLBP were included in this study. The patients were randomized into two
      groups. Group 1 (n=60) was given exercises only and accepted as the control
      group. Group 2 (n=61) received back school program and exercises. The exercise
      treatment was performed 3 days a week, for 3 months. The pain (visual analog
      scale, VAS), disability (Oswestry Disability Questionnaire, ODQ), walking
      performance (6 minute walking test, 6MWT), depression (Beck Depression Inventory
      scores, BDI), and QOL (Short Form 36, SF-36) of all participants were evaluated.
      The trunk and knee muscle strength were measured with a handheld dynamometer.
      Patients were assessed at baseline (BT), at the end of treatment (AT), and at the
      six month follow-up (F). RESULTS: Statistically significant improvements were
      found between groups regarding all of the clinical parameters over time. Pain,
      disability, muscle strength, endurance, 6MWT, mobility, QOL, and depression of
      both groups also showed improvements AT. These improvements persisted at 6-months
      follow-ups (P < 0.05). There were statistically significant differences between
      the groups for pain, disability, muscle strength, endurance, 6MWT, QOL, and
      depression regarding the change scores between AT-BT test and F-BT test (P <
      0.05). Group 2 improved more than group 1 except for mobility. CONCLUSION:
      Exercise programs can be modified and used successfully in CLBP and this effect
      can be increased with addition of back school further. LEVEL OF EVIDENCE:
      Diagnostic study Level-I-I (prospective study).

PMID- 24867907
TI  - Low back pain in adolescents. An assessment   of the quality of life in terms of
      qualitative   and quantitative pain variables.
AB  - BACKGROUND: Information concerning low back pain in adolescents with scoliosis is
      rather limited in literature. While the epidemiology of back pain at the age of
      adolescence has been described extensively, studies evaluating the effects of
      therapeutic interventions are still sparse. MATERIAL AND METHOD: The study was
      conducted in two groups with juvenile idiopathic scoliosis Io. The clinical group
      was 21 persons with low back pain and the control group was 11 persons without
      pain. In order to assess the quality of life and the level of pain We used the
      abridged version of WHOQOL (World Human Organizations Quality of Life
      questionnaire) and MPQSF (Short Form of McGill Pain questionnaire). The treatment
      consisted of a combination of manual therapy and rehabilitation exercises.
      RESULTS: We obtained a significant improvement in the area of the physical
      health: 7.17 in the clinical group (p = 0.000613); 6.12 for females (p =
      0.015400); 9.19 for males (p = 0.022311). The assessment of the quality of life
      was different between the clinical and the control groups. The decrease in pain
      in the clinical group was 5.71 (p = 0.000132), 5.93 for females (p = 0.001474)
      and 5.29 for males (p = 0.027709). Data represents more than a double decrease in
      strong and moderate pain. CONCLUSION: A combination of rehabilitation exercises
      and soft manual therapy is effective in reducing the low back pain in adolescents
      and enhancing the somatic facet of the quality of life.

PMID- 24867908
TI  - Evaluation of restless legs syndrome in fibromyalgia syndrome: an analysis of
      quality of sleep and life.
AB  - BACKGROUND AND OBJECTIVE: The aim of this study is to find prevalence and
      severity of restless legs syndrome (RLS) in patients with fibromyalgia syndrome
      (FMS) and detect effect of FMS and RLS coexistance on quality of sleep and life.
      METHODS: In this study, presence and severity of RLS were detected in patients
      with FMS and Pitsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS)
      and Fibromyalgia Impact Questionnaire (FIQ) scores of all patients were measured.
      RESULTS: One hundred and fifteen female patients with median age 49 (39.0
      57.0)[median (25-75{?%} interquartile range)] were included in the study. In
      42.6% of patients RLS coexisting with FMS was found. RLS was classified as
      moderate in 42.9% of patients and as severe in 49.0% of patients. In patients
      with FMS ans RLS sleep quality, daytime sleepiness and quality of life were more
      severely impaired (PSQI scores were 9.0 +/- 4.4 vs 7.8 +/- 4.3, p=0.003; ESS
      scores were 5.0(3.0-7.5) vs 3.0(1.0-4.3), p=0.036 and FIQ scores were 68.1 +/-
      9.8 vs 59.4 +/- 16.9, p=0.027) compared to patients with only FMS. Prevalence of
      RLS was found higher in FMS than normal population and quality of sleep and
      quality of life were worse in patients with RLS. CONCLUSIONS: Presence of RLS
      should be investigated in every patient with FMS and treatment plans should also
      cover RLS in case of coexistance with FMS. Prospective cohort studies are needed
      for better explanation of FMS and RLS coexistance.

PMID- 24867910
TI  - Retaining clinician-scientists: nature versus nurture.
AB  - In their IOVS article "Rejuvenating Clinician-Scientist Training" (published
      March 28, 2014), Balamurali Ambati and Judd Cahoon rightly point out the dearth
      of new clinician-scientists in ophthalmology. Within the context of their
      suggestions for increasing the number of successful clinician-scientists, they
      claim that the traditional MD-PhD training programs and K awards have failed to
      produce individuals who will carry on the important work of clinically relevant
      research that will improve patients' lives and sight. In this response we present
      data, including information on the career paths of graduates of the Washington
      University ophthalmology residency, that call into question the presumed failure
      of MD-PhD and K award programs and show that, in fact, graduates of these
      programs are more likely to succeed as clinician-scientists than are their peers
      who have not trained in such scientifically rigorous environments. We propose
      that, rather than a failure of early training programs, it may be obstacles that
      arise later in training and among junior faculty that prevent promising careers
      from reaching maturity. Funding, one rather large obstacle, takes the form of
      imbalanced start-up monies, less National Institutes of Health (NIH) funding
      awarded to young investigators, and study section composition that may work
      against those with clinically driven questions. We also explore the challenges
      faced in the culture surrounding residency and fellowship training. We agree with
      Ambati and Cahoon that there needs to be more innovation in the way training
      programs are structured, but we believe that the evidence supports supplementing
      the current model rather than scrapping it and starting over with unproven
      initiatives. The data on training programs supports the contention that those who
      have already made substantial investment and commitment to the clinician
      scientist pathway through participation in MSTP or K training programs are the
      most likely to succeed on this career trajectory. To muffle the siren song of
      private practice and retain those best prepared for the clinician-scientist
      pathway requires additional investment as their careers mature through protected
      research time, mentorship, and advocacy. 

PMID- 24867909
TI  - Physiological responses to psychological stress: importance of adiposity in men
      aged 50-70 years.
AB  - We tested the hypothesis that overweight/obese men aged 50-70 years will have a
      greater salivary cortisol, salivary alpha amylase and heart rate (HR) responses
      to psychological stress compared with age matched lean men. Lean (BMI=20-25
      kg/m(2); n=19) and overweight/obese (BMI=27-35 kg/m(2); n=17) men (50-70 years)
      were subjected to a well-characterised psychological stress (Trier Social Stress
      Test, TSST) at 1500 h. Concentrations of cortisol and alpha amylase were measured
      in saliva samples collected every 7-15 min from 1400 to 1700 h. HR was recorded
      using electrocardiogram. Body weight, BMI, percentage body fat, resting systolic
      and diastolic blood pressure and mean arterial pressure were significantly higher
      (P<0.05) in overweight/obese men compared with lean men. Both groups responded to
      the TSST with a substantial elevation in salivary cortisol (372%), salivary alpha
      amylase (123%) and HR (22%). These responses did not differ significantly between
      the groups (time*treatment interaction for salivary cortisol, salivary alpha
      amylase and HR; P=0.187, P=0.288, P=0.550, respectively). There were no
      significant differences between the groups for pretreatment values, peak height,
      difference between pretreatment values and peak height (reactivity) or area under
      the curve for salivary cortisol, salivary alpha amylase or HR (P>0.05 for all).
      The results showed that, for men with a moderate level of overweight/obesity who
      were otherwise healthy, the response of salivary cortisol, salivary alpha amylase
      and HR to acute psychological stress was not impaired. 

PMID- 24867911
TI  - Microcysts in the inner nuclear layer, a nonspecific SD-OCT sign of cystoid
      macular edema.
AB  - Recently, many authors have propagated the notion that a specific form of
      "microcystic macular edema" occurs in patients with optic neuritis and optic
      atrophy of various etiology and is due to retrograde synaptic degeneration. The
      finding is isolated to the inner nuclear layer on spectral-domain optical
      coherence tomography in most cases, and is present in a parafoveal,
      circumferential, and central macular distribution. This perspective critically
      reviews the evidence and suggests that inner nuclear layer cystoid changes are an
      early and nonspecific indicator of typical cystoid macular edema of any cause,
      and that the finding is likely not a distinct entity. 

PMID- 24867912
TI  - Splicing-correcting therapeutic approaches for retinal dystrophies: where
      endogenous gene regulation and specificity matter.
AB  - Splicing is an important and highly regulated step in gene expression. The
      ability to modulate it can offer a therapeutic option for many genetic disorders.
      Antisense-mediated splicing-correction approaches have recently been successfully
      exploited for some genetic diseases, and are currently demonstrating safety and
      efficacy in different clinical trials. Their application for the treatment of
      retinal dystrophies could potentially solve a vast panel of cases, as illustrated
      by the abundance of mutations that could be targeted and the versatility of the
      technique. In this review, we will give an insight of the different therapeutic
      strategies, focusing on the current status of their application for retinal
      dystrophies. 

PMID- 24867913
TI  - Is tau a prion-like protein?

PMID- 24867914
TI  - Lester (Skip) Binder (1949-2013): in the beginning was tau.

PMID- 24867916
TI  - Measuring shared decision making: a review of constructs, measures, and
      opportunities for cardiovascular care.

PMID- 24867917
TI  - Check it! A randomized pilot of a positive psychology intervention to improve
      adherence in adolescents with type 1 diabetes.
AB  - PURPOSE: The purpose of the current study was to pilot-test a positive psychology
      intervention to improve adherence to diabetes management in adolescents with type
      1 diabetes. METHODS: A total of 39 adolescents (ages, 13-17 years) with type 1
      diabetes and their caregivers were randomized to a positive psychology
      intervention (n = 20) or an attention control (education) intervention (n = 19).
      The intervention condition used positive psychology exercises (eg, gratitude,
      self-affirmation), small gifts, and parent affirmations to boost positive affect.
      Outcomes included frequency of blood glucose monitoring, quality of life, and
      glycemic control. RESULTS: No main effects for treatment were observed at the 6
      month follow-up. However, there was a significant association between
      adolescents' levels of positive affect and measures of adherence, including self
      report and meter downloads of glucose monitoring. CONCLUSIONS: The results from
      the current study support the assertion that positive affect in the context of
      diabetes education is an important factor to consider in adolescents with type 1
      diabetes.

PMID- 24867915
TI  - Mechanisms for the adverse effects of late gestational increases in maternal
      cortisol on the heart revealed by transcriptomic analyses of the fetal septum.
AB  - We have previously shown in sheep that 10 days of modest chronic increase in
      maternal cortisol resulting from maternal infusion of cortisol (1 mg/kg/day)
      caused fetal heart enlargement and Purkinje cell apoptosis. In subsequent studies
      we extended the cortisol infusion to term, finding a dramatic incidence of
      stillbirth in the pregnancies with chronically increased cortisol. To investigate
      effects of maternal cortisol on the heart, we performed transcriptomic analyses
      on the septa using ovine microarrays and Webgestalt and Cytoscape programs for
      pathway inference. Analyses of the transcriptomic effects of maternal cortisol
      infusion for 10 days (130 day cortisol vs 130 day control), or ~25 days (140 day
      cortisol vs 140 day control) and of normal maturation (140 day control vs 130 day
      control) were performed. Gene ontology terms related to immune function and
      cytokine actions were significantly overrepresented as genes altered by both
      cortisol and maturation in the septa. After 10 days of cortisol, growth factor
      and muscle cell apoptosis pathways were significantly overrepresented, consistent
      with our previous histologic findings. In the term fetuses (~25 days of cortisol)
      nutrient pathways were significantly overrepresented, consistent with altered
      metabolism and reduced mitochondria. Analysis of mitochondrial number by
      mitochondrial DNA expression confirmed a significant decrease in mitochondria.
      The metabolic pathways modeled as altered by cortisol treatment to term were
      different from those modeled during maturation of the heart to term, and thus
      changes in gene expression in these metabolic pathways may be indicative of the
      fetal heart pathophysiologies seen in pregnancies complicated by stillbirth,
      including gestational diabetes, Cushing's disease and chronic stress. 

PMID- 24867920
TI  - Recent trends in convergence-based smart healthcare service.

PMID- 24867918
TI  - "We are all gonna get diabetic these days": the impact of a living legacy of type
      2 diabetes on Hispanic young adults' diabetes care.
AB  - PURPOSE: The purpose of this study was to investigate how an intergenerational
      legacy of type 2 diabetes affected the knowledge, attitudes, and treatment
      strategies of Hispanic young adults with diabetes. METHODS: Eight Hispanic young
      adults (ages 18-30 years) participated in a series of in-home longitudinal
      qualitative interviews, and 11 of their family members completed single in-home
      interviews, regarding their diabetes management practices. Interview transcripts
      were analyzed thematically by a team of researchers. RESULTS: Five themes emerged
      that characterized the influence of an intergenerational legacy of diabetes on
      young adults: food and family (how meal preparation and eating are shared within
      families), doing together (activity participation is contingent on others'
      participation), knowledge and expectations (expectations for the future and
      understandings of diabetes are shaped by family members), miscarried helping
      (well-intentioned actions have negative consequences), and reciprocal support
      (children and parents support each other's diabetes care). CONCLUSIONS: Hispanic
      young adults' knowledge, attitudes, and self-care practices related to diabetes
      are strongly influenced by the diabetes management practices of family members
      with diabetes, which often depart from current standards of diabetes care. Care
      providers should consider family members as a potentially significant influence,
      either positive or negative, on the diabetes self-care practices of this
      population.

PMID- 24867921
TI  - The Importance of Being Absent: Auxin Minima Are Required for Axillary Meristem
      Formation.

PMID- 24867919
TI  - Sleep dysfunction and EEG alterations in mice overexpressing alpha-synuclein.
AB  - BACKGROUND: Sleep disruptions occur early and frequently in Parkinson's disease
      (PD). PD patients also show a slowing of resting state activity. Alpha-synuclein
      is causally linked to PD and accumulates in sleep-related brain regions. While
      sleep problems occur in over 75% of PD patients and severely impact the quality
      of life of patients and caregivers, their study is limited by a paucity of
      adequate animal models. OBJECTIVE: The objective of this study was to determine
      whether overexpression of wildtype alpha-synuclein could lead to alterations in
      sleep patterns reminiscent of those observed in PD by measuring sleep/wake
      activity with rigorous quantitative methods in a well-characterized genetic mouse
      model. METHODS: At 10 months of age, mice expressing human wildtype alpha
      synuclein under the Thy-1 promoter (Thy1-aSyn) and wildtype littermates underwent
      the subcutaneous implantation of a telemetry device (Data Sciences International)
      for the recording of electromyograms (EMG) and electroencephalograms (EEG) in
      freely moving animals. Surgeries and data collection were performed without
      knowledge of mouse genotype. RESULTS: Thy1-aSyn mice showed increased non-rapid
      eye movement sleep during their quiescent phase, increased active wake during
      their active phase, and decreased rapid eye movement sleep over a 24-h period, as
      well as a shift in the density of their EEG power spectra toward lower
      frequencies with a significant decrease in gamma power during wakefulness.
      CONCLUSIONS: Alpha-synuclein overexpression in mice produces sleep disruptions
      and altered oscillatory EEG activity reminiscent of PD, and this model provides a
      novel platform to assess mechanisms and therapeutic strategies for sleep
      dysfunction in PD.

PMID- 24867922
TI  - SAUR19 Links Auxin and Plasma Membrane H+-ATPases in Cell Expansion.

PMID- 24867925
TI  - Response to letter regarding article, "Archetypal Arg169Cys mutation in NOTCH3
      does not drive the pathogenesis in cerebral autosomal dominant arteriopathy with
      subcortical infarcts and leucoencephalopathy via a loss-of-function mechanism".

PMID- 24867924
TI  - Is more better? Using metadata to explore dose-response relationships in stroke
      rehabilitation.
AB  - BACKGROUND AND PURPOSE: Neurophysiological models of rehabilitation and recovery
      suggest that a large volume of specific practice is required to induce the
      neuroplastic changes that underlie behavioral recovery. The primary objective of
      this meta-analysis was to explore the relationship between time scheduled for
      therapy and improvement in motor therapy for adults after stroke by (1) comparing
      high doses to low doses and (2) using metaregression to quantify the dose
      response relationship further. METHODS: Databases were searched to find
      randomized controlled trials that were not dosage matched for total time
      scheduled for therapy. Regression models were used to predict improvement during
      therapy as a function of total time scheduled for therapy and years after stroke.
      RESULTS: Overall, treatment groups receiving more therapy improved beyond control
      groups that received less (g=0.35; 95% confidence interval, 0.26-0.45).
      Furthermore, increased time scheduled for therapy was a significant predictor of
      increased improvement by itself and when controlling for linear and quadratic
      effects of time after stroke. CONCLUSIONS: There is a positive relationship
      between the time scheduled for therapy and therapy outcomes. These data suggest
      that large doses of therapy lead to clinically meaningful improvements,
      controlling for time after stroke. Currently, trials report time scheduled for
      therapy as a measure of therapy dose. Preferable measures of dose would be active
      time in therapy or repetitions of an exercise.

PMID- 24867923
TI  - OPT3 Is a Phloem-Specific Iron Transporter That Is Essential for Systemic Iron
      Signaling and Redistribution of Iron and Cadmium in Arabidopsis.
AB  - Iron is essential for both plant growth and human health and nutrition. Knowledge
      of the signaling mechanisms that communicate iron demand from shoots to roots to
      regulate iron uptake as well as the transport systems mediating iron partitioning
      into edible plant tissues is critical for the development of crop
      biofortification strategies. Here, we report that OPT3, previously classified as
      an oligopeptide transporter, is a plasma membrane transporter capable of
      transporting transition ions in vitro. Studies in Arabidopsis thaliana show that
      OPT3 loads iron into the phloem, facilitates iron recirculation from the xylem to
      the phloem, and regulates both shoot-to-root iron signaling and iron
      redistribution from mature to developing tissues. We also uncovered an aspect of
      crosstalk between iron homeostasis and cadmium partitioning that is mediated by
      OPT3. Together, these discoveries provide promising avenues for targeted
      strategies directed at increasing iron while decreasing cadmium density in the
      edible portions of crops and improving agricultural productivity in iron
      deficient soils.

PMID- 24867926
TI  - Loss of venous integrity in cerebral small vessel disease: a 7-T MRI study in
      cerebral autosomal-dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy (CADASIL).
AB  - BACKGROUND AND PURPOSE: Previous pathological studies in humans or in animal
      models have shown alterations of small arteries and veins within white matter
      lesions in cerebral small vessel disease. We aimed to evaluate in vivo, the
      integrity of the cerebral venous network using high-resolution MRI both within
      and outside white matter hyperintensities in cerebral autosomal-dominant
      arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).
      METHODS: High-resolution T2*-weighted images were obtained at 7-T in 13 CADASIL
      patients with no or only mild symptoms and 13 age- and sex-matched controls.
      Macroscopic veins were automatically counted in the centrum semiovale and
      compared between patients and controls. In addition, T2* was compared between
      groups in the normal-appearing white matter. RESULTS: Vein density was found
      lower in CADASIL patients compared with that in controls (-14.6% in patients,
      P<0.001). This was detected both within and outside white matter
      hyperintensities. Mean T2*, that is presumably inversely related to the venous
      density, was also found increased in normal-appearing white matter of patients
      (+7.2%, P=0.006). All results were independent from the extent of white matter
      hyperintensities. CONCLUSIONS: A significant reduction in the number of visible
      veins was observed in the centrum semiovale of CADASIL patients both within and
      outside white matter hyperintensities, together with an increase of T2* in the
      normal-appearing white matter. Additional studies are needed to decipher the
      exact implication of such vasculature changes in the appearance of white matter
      lesions.

PMID- 24867927
TI  - Letter by Moccia et al regarding article, "Archetypal Arg169Cys mutation in
      NOTCH3 does not drive the pathogenesis in cerebral autosomal dominant
      arteriopathy with subcortical infarcts and leucoencephalopathy via a loss-of
      function mechanism".

PMID- 24867928
TI  - Influence of Miles City Line 1 on the United States Hereford population.
AB  - The goal of this research was to document the influence of Line 1 (L1) Hereford
      cattle, developed by the USDA at its research facility in Miles City, MT, on the
      U.S. Hereford population. The L1 Hereford population originated in 1934 and has
      been thereafter maintained as a closed herd at that location. Dissemination of
      germplasm began in 1948. Pedigree data for approximately 14 million cattle
      recorded by the American Hereford Association (AHA) were used. A preliminary
      experiment was conducted to establish sample size necessary to estimate the
      pedigree relationship between L1 and the recorded Hereford population. Five
      random samples of 100, 400, 500, and 3,000 calves were drawn from the sets of
      calves born in 1980, 1990, and 2000. Sampled calves were pseudo mated to L1 sires
      from the decades 1968 to 1978, 1978 to 1988, and 1988 to 1998, respectively.
      Inbreeding coefficients were calculated for the resulting "offspring" and the
      relationship of each sampled animal to L1 was taken to be twice the maximum
      inbreeding coefficient for the set of L1 sires used in the pseudo matings. Based
      on the results of this experiment, it was decided that a sample size of 400
      animals per replicate was sufficient to estimate the relationship between L1 and
      the general Hereford population recorded by the AHA. In a second experiment, 5
      sets of 400 animals were drawn from the AHA herdbook representing each year from
      1980 to 2008 and pseudo mated to L1 sires and their relationship to L1 calculated
      as described above. Over the period, the number of animals recorded by the AHA
      that were related to L1 increased by 1.69 +/- 0.07% per year. The L1 Hereford
      population was ancestral to 79% of Hereford cattle recorded in 2006 through 2008.
      The greatest concentration of animals related to L1 was in the Great Plains and
      eastern Corn Belt of the United States, but animals related to L1 were found in
      48 states. In a third experiment, 240 L1 Hereford cattle and 311 sires
      representative of the Hereford breed in the United States were genotyped using
      the Illumina BovineSNP50 BeadChip. Resulting genotypes were used to assess the
      probability that the animals sampled from the U.S. population were members of L1.
      The average probability of membership in L1 was 0.20 and the regression of
      genomic probability of membership on pedigree relationship was 1.73 +/- 0.11 (r =
      0.65). These results document the far-reaching and profound impact of a long-term
      research program. 

PMID- 24867929
TI  - The length of productive life can be modified through selection: an experimental
      demonstration in the rabbit.
AB  - The objective of this study was to assess the feasibility of selecting for
      functional longevity in rabbits, defined as an ability to delay involuntary
      culling. Functional longevity was measured as the total number of AI performed
      after the first kindling. Breeding values were estimated using a discrete
      survival model. Male parents were selected on the basis of their progeny test
      results, and the efficiency of selection was estimated in the second generation,
      as was the correlated response on reproduction traits. A total of 48 males were
      progeny tested, based on the longevity of 10 daughters bred in 2 different farms.
      Based on their estimated genetic merit, 5 "high longevity" (HL) and 5 "low
      longevity" (LL) males were selected divergently and produced a new generation (5
      bucks/sires and 10 daughters/bucks). A difference in longevity (+0.75 AI, i.e.,
      32 d) was observed between the 2 lines. In farm 1, the differences were mainly
      due to culling (26% in the LL line vs. 14% in the HL line) whereas mortality was
      similar in the 2 lines. In farm 2, mortality and culling were both higher in the
      LL line than in the HL line (33 vs. 15% and 19 vs. 7%, respectively). There was
      no difference between the 2 lines in terms of the reproduction traits recorded
      for each kindling. Nevertheless, because of the difference in the litter number
      between the 2 lines, the sum of young rabbits born alive per doe over her
      lifetime and the sum of young rabbits weaned per doe were higher in the HL line
      (+5 kits; P < 0.01). Selection for functional longevity using survival analysis
      is feasible for modifying lifetime reproduction traits. 

PMID- 24867930
TI  - Effect of essential fatty acid and zinc supplementation during pregnancy on birth
      intervals, neonatal piglet brain myelination, stillbirth, and preweaning
      mortality.
AB  - Omega fatty acids and zinc contribute to physiological pathways that could affect
      the farrowing process, stillbirth, preweaning mortality, and postweaning return
      to estrus. To determine effects of omega fatty acids and zinc on these
      reproductive traits, gilts were mated and fed either a control diet, a diet
      supplemented with 1.09% Gromega, a diet supplemented with 0.07% zinc sulfate, or
      a diet supplemented with both Gromega and zinc sulfate from d 80 of gestation
      until farrowing. Farrowings were video recorded to obtain birth intervals for
      each piglet, and the number of live and stillborn piglets was recorded. On d 1
      after farrowing, piglets were weighed, and the smallest piglet in each litter was
      sacrificed. A blood sample was collected to measure the immunoglobulin immunocrit
      ratio, and brain, cerebellum, brain stem, full and empty stomach (to calculate
      stomach content weight), and heart weights were recorded. Because myelination of
      specific brain regions may affect preweaning mortality, brain stem, cerebellum,
      and spinal cord tissues were measured for content of myelin basic proteins and
      myelin lipids. For remaining piglets, survival to weaning and weaning weights
      were recorded. Results indicated a weak positive correlation (r = 0.23, P < 0.05)
      between immunocrit values and brain stem high molecular weight myelin basic
      protein. There was also a Gromega * zinc supplementation interaction (P < 0.05)
      on brain stem high molecular weight myelin basic protein in which the combined
      treatment was greater than the control or each supplement alone. Zinc treatment
      decreased stillbirth rate during prolonged farrowing and subsequent preweaning
      survival of low birth weight piglets. Gromega increased overall stillbirth rate
      and increased the stillbirth rate during prolonged farrowing. There were no
      relationships between myelin measurements and preweaning survival. In conclusion,
      combined Gromega and zinc supplementation appeared to improve myelination, but
      zinc alone improved stillbirth and preweaning survival. 

PMID- 24867931
TI  - Measures of the ovaries and uterus during development of gilts selected for
      differences in uterine capacity.
AB  - Direct selection for uterine capacity (UC) increased the number of live pigs
      born. A method to indirectly estimate UC in developing gilts is needed for this
      trait to be incorporated into commercial selection strategies. We tested the
      hypothesis that selection for UC alters phenotypic characteristics of the
      reproductive tract of prepubertal gilts and that these changes could be estimated
      in live animals using transrectal ultrasound (TRU). Gilts from lines selected for
      UC and a randomly selected control (CO) line were submitted for TRU at 130, 150,
      or 170 d of age and harvested 24 h later (n = 10 gilts/line per age). Diameter of
      the uterine horn was measured (2 to 4 measurements per animal) at TRU. At
      harvest, measurements of the ovary (height, width, length, weight, and number of
      visible follicles >1 mm) and uterine horn (weight, length, diameter, and
      endometrial diameter) were taken. There was no line * age interaction for any of
      the traits. All ovarian traits increased (P < 0.03) with age. Weight and length
      of the uterine horn was not different at 130 or 150 d but were increased (P <
      0.01) at 170 d of age. Diameter of the uterine horn tended (P = 0.06) to be
      increased at 170 d compared with 130 or 150 d, but age did not affect (P = 0.38)
      endometrial diameter. Ovarian weight and width were increased (P < 0.01) and
      ovarian length and height tended (P = 0.07) to be greater for UC than CO gilts,
      but the number of visible follicles did not differ. The UC gilts had increased (P
      < 0.02) weight of uterine horns, which tended (P = 0.09) to be longer than in the
      CO gilts. Diameter of the uterine horn and the endometrium were greater (P <
      0.01) for UC gilts than for CO gilts. Uterine horn diameter measured with TRU was
      not affected by age or line and was not highly correlated with any of the
      measured traits. Selection for increased UC results in larger ovaries and uterine
      horns, but TRU was not useful for estimating these traits in gilts of the age
      studied. 

PMID- 24867932
TI  - In vitro hydrolytic digestion, glycemic response in dogs, and true metabolizable
      energy content of soluble corn fibers.
AB  - The objective of this research was to measure in vitro hydrolytic digestion,
      glycemic and insulinemic responses in dogs, and true ME (TMEn) content of select
      soluble corn fibers (SCF) in roosters. The first generation (G1) SCF included
      hydrochloric acid-treated corn syrup (G1-CS-HCl), an SCF with an increased total
      dietary fiber (TDF) content (G1-SCF-HCl), an SCF that was spray-dried (G1-SCF
      SD), and a hydrogenated SCF (G1-SCF-hydrog). The second generation (G2) SCF
      included those prepared using phosphoric acid catalyzation in both a liquid [G2
      SCF-phos (Lq)] and powder [G2-SCF-phos (Pw)] form, and SCF that were prepared
      using hydrochloric acid catalyzation in both a liquid [G2-SCF-HCl (Lq)] and
      powder [G2-SCF-HCl (Pw)] form. Also, in the G2 set of samples were SCF prepared
      using the same method, but in 3 separate batches, all of which contained 70% TDF
      and 15% sugars. Two were in liquid form [G2-SCF-phos+HCl (Lq1)] and [G2-SCF
      phos+HCl (Lq2)], and one in powder form ([G2-SCF-phos+HCl (Pw)]. A lower sugar
      form (80% TDF and 5% sugar) of SCF was also evaluated (G2-SCF-low sugar). Glucose
      was the major free sugar and bound monosaccharide in all SCF except for G1-SCF
      hydrog that had greater concentrations of sorbitol. All SCF had intermediate to
      low amounts of monosaccharides released as a result of in vitro hydrolytic
      digestion, with glucose being the primary sugar component released. The G1-SCF
      were more digestible in vitro (approximately 50%) compared to G2-SCF
      (approximately 32%). All SCF had attenuated glycemic responses in adult dogs
      compared to a maltodextrin control (P < 0.05). The G2-SCF, on average, had lower
      glycemic responses and TMEn values in roosters than G1-SCF. All SCF had low free
      sugar concentrations with varying degrees of resistance to digestion, reduced
      caloric content, and attenuated glycemic and insulinemic responses in adult dogs.
      These ingredients are potential candidates for inclusion in reduced calorie and
      low glycemic canine diets. 

PMID- 24867933
TI  - Energy and nutrient deposition and excretion in the reproducing sow: model
      development and evaluation.
AB  - Air and nutrient emissions from swine operations raise environmental concerns.
      During the reproduction phase, sows consume and excrete large quantities of
      nutrients. The objective of this study was to develop a mathematical model to
      describe energy and nutrient partitioning and predict manure excretion and
      composition and methane emissions on a daily basis. The model was structured to
      contain gestation and lactation modules, which can be run separately or
      sequentially, with outputs from the gestation module used as inputs to the
      lactation module. In the gestating module, energy and protein requirements for
      maintenance, and fetal and maternal growth were described. In the lactating
      module, a factorial approach was used to estimate requirements for maintenance,
      milk production, and maternal growth. The priority for nutrient partitioning was
      assumed to be in the order of maintenance, milk production, and maternal growth
      with body tissue losses constrained within biological limits. Global sensitivity
      analysis showed that nonlinearity in the parameters was small. The model outputs
      considered were the total protein and fat deposition, average urinary and fecal N
      excretion, average methane emission, manure carbon excretion, and manure
      production. The model was evaluated using independent data sets from the
      literature using root mean square prediction error (RMSPE) and concordance
      correlation coefficients. The gestation module predicted body fat gain better
      than body protein gain, which was related to predictions of body fat and protein
      loss from the lactation model. Nitrogen intake, urine N, fecal N, and milk N were
      predicted with RMSPE as percentage of observed mean of 9.7, 17.9, 10.0, and 7.7%,
      respectively. The model provided a framework, but more refinements and
      improvements in accuracy of prediction (particularly urine N) are required before
      the model can be used to assess environmental mitigation options from sow
      operations. 

PMID- 24867934
TI  - Standardized total tract digestibility of phosphorus in copra meal, palm kernel
      expellers, palm kernel meal, and soybean meal fed to growing pigs.
AB  - Sixty-six barrows (initial BW: 27.4 +/- 2.8 kg) were used to determine the
      standardized total tract digestibility (STTD) of P in copra meal (CM), palm
      kernel expellers from Indonesia (PKE-IN), palm kernel expellers from Costa Rica
      (PKE-CR), palm kernel meal from Costa Rica (PKM), and soybean meal (SBM) without
      or with exogenous phytase. Pigs were housed individually in metabolism cages and
      allotted to 11 diets with 6 replicate pigs per diet in a generalized randomized
      block design. Five diets were formulated by mixing cornstarch and sugar with CM,
      PKE-IN, PKE-CR, PKM, or SBM. Five additional diets, which were identical to the
      initial 5 diets but supplemented with 800 units of phytase, were also formulated.
      A P-free diet was used to measure basal endogenous losses of P by the pigs. Feces
      were collected for 5 d using the marker to marker approach after a 5-d adaptation
      period. Analyzed total P in CM, PKE-IN, PKE-CR, PKM, and SBM was 0.52, 0.51,
      0.53, 0.54, and 0.67%, respectively. Phytate P was 0.22, 0.35, 0.38, 0.32, and
      0.44% in CM, PKE-IN, PKE-CR, PKM, and SBM, respectively. Addition of phytase
      increased (P < 0.05) the apparent total tract digestibility (ATTD) of P from 60.6
      to 80.8, 27.3 to 56.5, 32.6 to 59.9, 48.9 to 64.1, and 41.1 to 72.2% in CM, PKE
      IN, PKE-CR, PKM, and SBM, respectively. The ATTD of P in CM was greater (P <
      0.05) than in any of the other ingredients. The ATTD of P in SBM and PKM was
      greater (P < 0.05) than in PKE-IN, with PKE-CR being intermediate. The STTD of P
      increased (P < 0.05) from 70.6 to 90.3, 37.6 to 66.4, 43.2 to 69.9, 57.9 to 73.5,
      and 49.6 to 81.1% in CM, PKE-IN, PKE-CR, PKM, and SBM, respectively, when
      microbial phytase was added to the diets. When expressed as a percentage of total
      P, phytate P concentration in the ingredient negatively affected (P < 0.05) the
      ATTD of P (107.09 - 1.0564 * % phytate P; R(2) = 87.1) and the STTD of P (116.3 -
      1.0487 * % phytate P; R(2) = 89.4). In conclusion, microbial phytase increased P
      digestibility of CM, PKM, PKE-CR, PKE-IN, and SBM when fed to growing pigs, and
      the concentration of phytate P affects the response to microbial phytase. 

PMID- 24867935
TI  - Poor weaning transition average daily gain in pigs is not correlated with
      pathological or immunological markers of enteric disease during a porcine
      reproductive and respiratory syndrome virus outbreak.
AB  - Previous research suggests that enteric disease and poor gut health interact to
      decrease pig performance. Our objective was to determine if light birth weight
      pigs or those from the bottom 10th percentile of transition ADG (tADG) have a
      higher incidence of pathogen presence or enteric lesions than heavier or faster
      growing contemporaries. A total of 1,500 pigs were weighed at birth and divided
      into 5 birth weight (BRW) categories: <1, 1 to 1.25, 1.26 to 1.5, 1.51 to 1.75,
      and >1.76 kg. At weaning, 1,054 random pigs were moved to a commercial wean-to
      finish barn. Pigs were weighed individually at 0 and 3 wk postweaning. Transition
      ADG was calculated as the ADG between wk 0 and 3 postweaning. One pig from each
      of the 10th, 30th, and 70th percentiles of tADG was used to create 1 set of 3
      pigs with the same litter size and from the same parity sow. Forty pigs from each
      of the 3 tADG percentiles were matched for sex, litter size, and sow parity but
      not BRW to create 20 matched sets of 60 pigs. This allowed for the main effects
      of BRW and tADG to be studied as a 5 * 3 factorial design. At 3 and 22 wk
      postweaning, pigs were euthanized for organ system tissue evaluation. Lung, lymph
      node, and digesta were analyzed for presence of pathogens and for severity of
      microscopic lesions (0 = not present, 1 = present, with slight erosion, 2 =
      present, with moderate erosion, and 3 = present and severe erosion). Data were
      analyzed using PROC GENMOD and GLIMMIX, where pig served as the experimental
      unit. The fixed effects were BRW and tADG and the random effects were pen and
      set. There were no BRW * tADG interactions (P = 0.16). There was no correlation
      (P = 0.12) between tADG and pathogen presence at either 3 or 22 wk postweaning.
      Incidence and severity of microscopic lesions in the large intestine at 3 wk
      postweaning decreased linearly with increasing tADG (P = 0.01). Lesion incidence
      and severity were also affected (P < 0.04) by tADG at 22 wk postweaning, with
      greater stomach incidence in the 10th percentile. Birth weight affected (P =
      0.02) haemolytic Escherichia coli and Salmonella spp. B (includes Salmonella
      typhimurium) isolation at 3 wk postweaning as well as Brachyspira spp. isolation
      at 22 wk postweaning (P = 0.05) but in mixed directions. There were no effects (P
      = 0.21) of BRW or tADG on serum or ileum mucosa immune markers. In summary, it is
      apparent from this research that neither BRW nor tADG are likely causes of
      pathogen or lesion incidence. 

PMID- 24867936
TI  - Effect of vaccination against foot-and-mouth disease on growth performance of
      Korean native goat (Capra hircus coreanae).
AB  - The objectives of this study were 1) to evaluate the effects of vaccination
      against foot-and-mouth disease (FMD) on growth performance, nutrient
      digestibility, hematological parameters, and behavior in a ruminant animal and 2)
      to investigate a possible strategy for reducing its adverse effect. A total of 12
      Korean native goats (Capra hircus coreanae; 19.8 +/- 2.9 kg) were used in a
      crossover design with 3 experimental periods and 3 treatments, randomized and
      balanced for counteracting possible carry-over effects. The treatments were 1)
      control, 2) co-injection with a commercially available dipyrone (CADI), and 3)
      supplementation with gamma-amino butyric acid (GABA) at 10 g/kg in concentrate
      mix. Each period lasted 4 wk, and the vaccination against FMD was performed at 2
      wk after the start of each period. The goats were individually housed in a
      metabolic cage and fed ad libitum with a diet consisting of bermuda grass and
      commercial concentrate mix (6:4, wt/wt). Dry matter intake, ADG, nutrients
      digestibility, hematological parameters, and behavioral activities of the goats
      were measured before and after vaccination. Although DMI was not decreased (P >
      0.05), ADG was decreased by the vaccination to the goats (P < 0.01). The total
      number of leukocytes was increased while that of erythrocytes was decreased by
      the FMD vaccination (P < 0.01). The vaccination shortened standing time while
      extended lying time and the time spent in drinking (P < 0.05). The treatment by
      CADI reduced the adverse effect of vaccination on ADG and goat behavior compared
      with control and GABA treatment (P < 0.05). We concluded that the FMD vaccination
      decreased ADG of the goats without depression of diet intake, and CADI may
      attenuate the adverse effect of the FMD vaccination. 

PMID- 24867937
TI  - Effects of trace mineral injections on measures of performance and trace mineral
      status of pre- and postweaned beef calves.
AB  - Three experiments were conducted to examine the effects of injectable trace
      minerals (ITM) on measures of trace mineral status and performance in pre- and
      postweaned Brangus-crossbred beef calves. In Exp. 1, calves were assigned to
      treatments in alternating birth order (n = 150; 75/treatment), consisting of a 1
      mL subcutaneous injection of ITM (MultiMin 90; MultiMin USA, Inc., Fort Collins,
      CO) or sterile saline. The ITM formulation consisted of 60, 10, 15, and 5 mg/mL
      of Zn, Mn, Cu, and Se. Treatments were readministered at 100 and 200 d of age.
      Calf BW was recorded at birth and on d 100, 150, 200, and 250 (weaning). Trace
      mineral status was assessed in liver biopsy samples (n = 12/treatment) collected
      on d 150, 200, and 250. Administration of ITM had no impact on BW gain (P >=
      0.55) but did result in greater (P <= 0.02) concentrations of liver Cu and Se and
      lesser (P = 0.05) liver Fe concentrations compared to saline-injected calves. In
      Exp. 2, 24 heifers were selected from the weaned calves of Exp. 1 (n =
      12/treatment) and transported 1,600 km. Remaining on their original treatments,
      heifers were administered 5 mL of ITM or saline following transport (d 0). Blood
      samples, for acute phase protein (APP) analysis, were collected on d 0, 1, 3, 6,
      9, and 13 and liver biopsy samples for assessment of trace mineral status on d
      13. Plasma APP concentrations increased in all calves following weaning and
      transport but concentrations were greatest (P < 0.05) in ITM- vs. saline-injected
      heifers on d 6 and 9. Liver concentrations of Cu, Se, and Zn were greater (P <=
      0.04) but ADG lesser (P = 0.05) for heifers receiving ITM vs. saline. In Exp. 3,
      34 heifers, without previous exposure to ITM, were enrolled in a 177-d
      development study (n = 17/treatment). Treatments consisted of 2.5-mL injections
      of ITM or sterile saline on d 0, 51, and 127. Humoral immune response to an
      injection of porcine red blood cells (PRBC) was evaluated on d 51. Trace mineral
      status was evaluated in liver biopsy samples collected on d 177. Overall heifer
      ADG, PRBC antibody titers, and liver Se concentrations were greatest (P <= 0.06)
      for ITM vs. control heifers. Collectively, these studies demonstrate an increased
      trace mineral status, a greater humoral response to novel antigen, and a
      heightened APP response to weaning and transport stress in pre- and postweaned
      beef calves administered ITM. 

PMID- 24867938
TI  - Predicting dry matter intake by growing and finishing beef cattle: evaluation of
      current methods and equation development.
AB  - The NRC (1996) equation for predicting DMI by growing-finishing beef cattle,
      which is based on dietary NEm concentration and average BW(0.75), has been
      reported to over- and underpredict DMI depending on dietary and animal
      conditions. Our objectives were to 1) develop broadly applicable equations for
      predicting DMI from BW and dietary NEm concentration and 2) evaluate the
      predictive value of using NE requirements and dietary NE concentrations to
      determine the DMI required (DMIR) by feedlot cattle. Two new DMI prediction
      equations were developed from a literature data set, which represented treatment
      means from published experiments from 1980 to 2011 that covered a wide range of
      dietary NEm concentrations. Dry matter intake predicted from the 2 new equations,
      which were based on NEm concentration and either the ending BW for a feeding
      period or the DMI per unit of average BW (End BW and DMI/BW, respectively),
      accounted for 61 and 58% of the variation in observed DMI, respectively, vs. 48%
      for the 1996 NRC equation. When validated with 4 independent data sets that
      included 7,751 pen and individual observations of DMI by animals of varying BW
      and feeding periods of varying length, DMI predicted by the 1996 NRC equation,
      the End BW and DMI/BW equations, and the DMIR method accounted for 13.1 to 82.9%
      of the variation in observed DMI, with higher r(2) values for 2 feedlot pen data
      sets and lower values for pen and individual data sets that included animals on
      lower-energy, growing diets as well as those in feedlot settings. The DMIR method
      yielded the greatest r(2) values and least prediction errors across the 4 data
      sets; however, mean biases (P < 0.01) were evident for all the equations across
      the data sets, ranging from as high as 1.01 kg for the DMIR method to -1.03 kg
      for the 1996 NRC equation. Negative linear bias was evident in virtually all
      cases, suggesting that prediction errors changed as DMI increased. Despite the
      expanded literature database for equation development, other than a trend for
      lower standard errors of prediction with the DMI/BW equation, the 2 new equations
      did not offer major advantages over the 1996 NRC equation when applied to the
      validation data sets. Because the DMIR approach accounted for the greatest
      percentage of variation in observed DMI and had the least root mean square error
      values in all data sets evaluated, this approach should be considered as a means
      of predicting DMI by growing-finishing beef cattle. 

PMID- 24867940
TI  - Methodological aspects of whole-genome bisulfite sequencing analysis.
AB  - The combination of DNA bisulfite treatment with high-throughput sequencing
      technologies has enabled investigation of genome-wide DNA methylation beyond CpG
      sites and CpG islands. These technologies have opened new avenues to understand
      the interplay between epigenetic events, chromatin plasticity and gene
      regulation. However, the processing, managing and mining of this huge volume of
      data require specialized computational tools and statistical methods that are yet
      to be standardized. Here, we describe a complete bisulfite sequencing analysis
      workflow, including recently developed programs, highlighting each of the crucial
      analysis steps required, i.e. sequencing quality control, reads alignment,
      methylation scoring, methylation heterogeneity assessment, genomic features
      annotation, data visualization and determination of differentially methylated
      cytosines. Moreover, we discuss the limitations of these technologies and
      considerations to perform suitable analyses. 

PMID- 24867941
TI  - MIPgen: optimized modeling and design of molecular inversion probes for targeted
      resequencing.
AB  - Molecular inversion probes (MIPs) enable cost-effective multiplex targeted gene
      resequencing in large cohorts. However, the design of individual MIPs is a
      critical parameter governing the performance of this technology with respect to
      capture uniformity and specificity. MIPgen is a user-friendly package that
      simplifies the process of designing custom MIP assays to arbitrary targets. New
      logistic and SVM-derived models enable in silico predictions of assay success,
      and assay redesign exhibits improved coverage uniformity relative to previous
      methods, which in turn improves the utility of MIPs for cost-effective targeted
      sequencing for candidate gene validation and for diagnostic sequencing in a
      clinical setting. AVAILABILITY AND IMPLEMENTATION: MIPgen is implemented in C++.
      Source code and accompanying Python scripts are available at
      http://shendurelab.github.io/MIPGEN/.

PMID- 24867942
TI  - keeSeek: searching distant non-existing words in genomes for PCR-based
      applications.
AB  - The search for short words that are absent in the genome of one or more organisms
      (neverwords, also known as nullomers) is attracting growing interest because of
      the impact they may have in recent molecular biology applications. keeSeek is
      able to find absent sequences with primer-like features, which can be used as
      unique labels for exogenously inserted DNA fragments to recover their exact
      position into the genome using PCR techniques. The main differences with respect
      to previously developed tools for neverwords generation are (i) calculation of
      the distance from the reference genome, in terms of number of mismatches, and
      selection of the most distant sequences that will have a low probability to
      anneal unspecifically; (ii) application of a series of filters to discard
      candidates not suitable to be used as PCR primers. KeeSeek has been implemented
      in C++ and CUDA (Compute Unified Device Architecture) to work in a General
      Purpose Computing on Graphics Processing Units (GPGPU) environment. AVAILABILITY
      AND IMPLEMENTATION: Freely available under the Q Public License at
      http://www.medcomp.medicina.unipd.it/main_site/doku.php?id=keeseek.

PMID- 24867943
TI  - CWig: compressed representation of Wiggle/BedGraph format.
AB  - MOTIVATION: BigWig, a format to represent read density data, is one of the most
      popular data types. They can represent the peak intensity in ChIP-seq, the
      transcript expression in RNA-seq, the copy number variation in whole genome
      sequencing, etc. UCSC Encode project uses the bigWig format heavily for storage
      and visualization. Of 5.2 TB Encode hg19 database, 1.6 TB (31% of the total
      space) is used to store bigWig files. BigWig format not only saves a lot of space
      but also supports fast queries that are crucial for interactive analysis and
      browsing. In our benchmark, bigWig often has similar size to the gzipped raw
      data, while is still able to support ~ 5000 random queries per second. RESULTS:
      Although bigWig is good enough at the moment, both storage space and query time
      are expected to become limited when sequencing gets cheaper. This article
      describes a new method to store density data named CWig. The format uses on
      average one-third of the size of existing bigWig files and improves random query
      speed up to 100 times. AVAILABILITY AND IMPLEMENTATION:
      http://genome.ddns.comp.nus.edu.sg/~cwig.

PMID- 24867945
TI  - Stroke in young women: An interpretative phenomenological analysis.
AB  - Stroke among adults of working age is increasing. We aimed to explore the
      experience of stroke among young women in Ireland. In total, 12 women (aged
      between 18 and 50 years) participated in semi-structured interviews. Data were
      analysed using interpretative phenomenological analysis. Four super-ordinate
      themes were identified: stroke as an illness of later life ('obviously it's for
      older people'), post-stroke selves, a desire for peer support and the impact of
      stroke on relationships. Findings indicate the importance of addressing the
      specific needs of younger stroke patients from admission to recovery through
      provision of inclusive all-age acute stroke services with tailored
      rehabilitation.

PMID- 24867944
TI  - Impact of ultraviolet radiation treatments on the physicochemical properties,
      antioxidants, enzyme activity and microbial load in freshly prepared hand pressed
      strawberry juice.
AB  - Freshly prepared, hand-pressed strawberry fruit juice was exposed to ultraviolet
      radiation (254 nm) at room temperature (25 C +/- 1 C) for 15, 30 and 60 min with
      0 min serving as control. Results revealed decrease in pH, total soluble solids
      and titratable acidity, while colour parameters (L*, a* and b* values) and
      clarity of juice (% transmittance) increased significantly. All the results
      corresponded to exposure time to ultraviolet radiation. Bioactive compounds
      (total phenolics, ascorbic acid and anthocyanins) decreased along with a recorded
      reduction in polyphenol oxidase enzyme and 1,1-diphenyl-2-picryl hydrazyl radical
      scavenging activities, which were again dependent on exposure time. Results on
      the microbial studies showed significant reduction by 2-log cycles in aerobic
      plate count as well as in total yeast and mould counts. Though negative results
      were observed for certain parameters, this is the first time it was endeavoured
      to demonstrate the impact of ultraviolet radiation radiation on freshly prepared,
      hand-pressed strawberries juice. 

PMID- 24867946
TI  - Wanderings in biochemistry.
AB  - My Ph.D. thesis in the laboratory of Severo Ochoa at New York University School
      of Medicine in 1962 included the determination of the nucleotide compositions of
      codons specifying amino acids. The experiments were based on the use of random
      copolyribonucleotides (synthesized by polynucleotide phosphorylase) as messenger
      RNA in a cell-free protein-synthesizing system. At Yale University, where I
      joined the faculty, my co-workers and I first studied the mechanisms of protein
      synthesis. Thereafter, we explored the interferons (IFNs), which were discovered
      as antiviral defense agents but were revealed to be components of a highly
      complex multifunctional system. We isolated pure IFNs and characterized IFN
      activated genes, the proteins they encode, and their functions. We concentrated
      on a cluster of IFN-activated genes, the p200 cluster, which arose by repeated
      gene duplications and which encodes a large family of highly multifunctional
      proteins. For example, the murine protein p204 can be activated in numerous
      tissues by distinct transcription factors. It modulates cell proliferation and
      the differentiation of a variety of tissues by binding to many proteins. p204
      also inhibits the activities of wild-type Ras proteins and Ras oncoproteins. 

PMID- 24867947
TI  - Epigenetic modifications and canonical wingless/int-1 class (WNT) signaling
      enable trans-differentiation of nonosteogenic cells into osteoblasts.
AB  - Mesenchymal cells alter and retain their phenotype during skeletal development
      through activation or suppression of signaling pathways. For example, we have
      shown that Wnt3a only stimulates osteoblast differentiation in cells with
      intrinsic osteogenic potential (e.g. MC3T3-E1 pre-osteoblasts) and not in fat
      cell precursors or fibroblasts (3T3-L1 pre-adipocytes or NIH3T3 fibroblasts,
      respectively). Wnt3a promotes osteogenesis in part by stimulating autocrine
      production of the osteoinductive ligand Bmp2. Here, we show that the promoter
      regions of the genes for Bmp2 and the osteoblast marker Alp are epigenetically
      locked to prevent their expression in nonosteogenic cells. Both genes have
      conserved CpG islands that exhibit increased CpG methylation, as well as
      decreased acetylation and increased methylation of histone H3 lysine 9 (H3-K9)
      specifically in nonosteogenic cells. Treatment of pre-adipocytes or fibroblasts
      with the CpG-demethylating agent 5'-aza-2'-deoxycytidine or the histone
      deacetylase inhibitor trichostatin-A renders Bmp2 and Alp responsive to Wnt3a.
      Hence, drug-induced epigenetic activation of Bmp2 gene expression contributes to
      Wnt3a-mediated direct trans-differentiation of pre-adipocytes or fibroblasts into
      osteoblasts. We propose that direct conversion of nonosteogenic cells into
      osteoblastic cell types without inducing pluripotency may improve prospects for
      novel epigenetic therapies to treat skeletal afflictions. 

PMID- 24867948
TI  - FIH-1-Mint3 axis does not control HIF-1 transcriptional activity in nucleus
      pulposus cells.
AB  - The objective of this study was to determine the role of FIH-1 in regulating HIF
      1 activity in the nucleus pulposus (NP) cells and the control of this regulation
      by binding and sequestration of FIH-1 by Mint3. FIH-1 and Mint3 were both
      expressed in the NP and were shown to strongly co-localize within the cell
      nucleus. Although both mRNA and protein expression of FIH-1 decreased in hypoxia,
      only Mint3 protein levels were hypoxiasensitive. Overexpression of FIH-1 was able
      to reduce HIF-1 function, as seen by changes in activities of hypoxia response
      element-luciferase reporter and HIF-1-C-TAD and HIF-2-TAD. Moreover, co
      transfection of either full-length Mint3 or the N terminus of Mint3 abrogated FIH
      1-dependent reduction in HIF-1 activity under both normoxia and hypoxia. Nuclear
      levels of FIH-1 and Mint3 decreased in hypoxia, and the use of specific nuclear
      import and export inhibitors clearly showed that cellular compartmentalization of
      overexpressed FIH-1 was critical for its regulation of HIF-1 activity in NP
      cells. Interestingly, microarray results after stable silencing of FIH-1 showed
      no significant changes in transcripts of classical HIF-1 target genes. However,
      expression of several other transcripts, including those of the Notch pathway,
      changed in FIH-1-silenced cells. Moreover, co-transfection of Notch-ICD could
      restore suppression of HIF-1-TAD activity by exogenous FIH-1. Taken together,
      these results suggest that, possibly due to low endogenous levels and/or
      preferential association with substrates such as Notch, FIH-1 activity does not
      represent a major mechanism by which NP cells control HIF-1-dependent
      transcription, a testament to their adaptation to a unique hypoxic niche.

PMID- 24867949
TI  - Neutrophils generate microparticles during exposure to inert gases due to
      cytoskeletal oxidative stress.
AB  - This investigation was to elucidate the mechanism for microparticle (MP)
      formation triggered by exposures to high pressure inert gases. Human neutrophils
      generate MPs at a threshold of ~186 kilopascals with exposures of 30 min or more.
      Murine cells are similar, but MP production occurs at a slower rate and continues
      for ~4 h, whether or not cells remain under pressure. Neutrophils exposed to
      elevated gas but not hydrostatic pressure produce MPs according to the potency
      series: argon ? nitrogen > helium. Following a similar pattern, gases activate
      type-2 nitric-oxide synthase (NOS-2) and NADPH oxidase (NOX). MP production does
      not occur with neutrophils exposed to a NOX inhibitor (Nox2ds) or a NOS-2
      inhibitor (1400W) or with cells from mice lacking NOS-2. Reactive species cause S
      nitrosylation of cytosolic actin that enhances actin polymerization. Protein
      cross-linking and immunoprecipitation studies indicate that increased
      polymerization occurs because of associations involving vasodilator-stimulated
      phosphoprotein, focal adhesion kinase, the H(+)/K(+) ATPase beta (flippase), the
      hematopoietic cell multidrug resistance protein ABC transporter (floppase), and
      protein-disulfide isomerase in proximity to short actin filaments. Using chemical
      inhibitors or reducing cell concentrations of any of these proteins with small
      inhibitory RNA abrogates NOS-2 activation, reactive species generation, actin
      polymerization, and MP production. These effects were also inhibited in cells
      exposed to UV light, which photoreverses S-nitrosylated cysteine residues and by
      co-incubations with the antioxidant ebselen or cytochalasin D. The autocatalytic
      cycle of protein activation is initiated by inert gas-mediated singlet O2
      production. 

PMID- 24867950
TI  - Directed expression of a chimeric type II keratin partially rescues keratin 5
      null mice.
AB  - The crucial role of structural support fulfilled by keratin intermediate
      filaments (IFs) in surface epithelia likely requires that they be organized into
      cross-linked networks. For IFs comprised of keratins 5 and 14 (K5 and K14), which
      occur in basal keratinocytes of the epidermis, formation of cross-linked bundles
      is, in part, self-driven through cis-acting determinants. Here, we targeted the
      expression of a bundling-competent KRT5/KRT8 chimeric cDNA (KRT8bc) or bundling
      deficient wild type KRT8 as a control to the epidermal basal layer of Krt5-null
      mice to assess the functional importance of keratin IF self-organization in vivo.
      Such targeted expression of K8bc rescued Krt5-null mice with a 47% frequency,
      whereas K8 completely failed to do so. This outcome correlated with lower than
      expected levels of K8bc and especially K8 mRNA and protein in the epidermis of
      E18.5 replacement embryos. Ex vivo culture of embryonic skin keratinocytes
      confirmed the ability of K8bc to form IFs in the absence of K5. Additionally,
      electron microscopy analysis of E18.5 embryonic skin revealed that the striking
      defects observed in keratin IF bundling, cytoarchitecture, and mitochondria are
      partially restored by K8bc expression. As young adults, viable KRT8bc replacement
      mice develop alopecia and chronic skin lesions, indicating that the skin
      epithelia are not completely normal. These findings are consistent with a
      contribution of self-mediated organization of keratin IFs to structural support
      and cytoarchitecture in basal layer keratinocytes of the epidermis and underscore
      the importance of context-dependent regulation for keratin genes and proteins in
      vivo. 

PMID- 24867951
TI  - Activated hepatic stellate cells are dependent on self-collagen, cleaved by
      membrane type 1 matrix metalloproteinase for their growth.
AB  - Stellate cells are distributed throughout organs, where, upon chronic damage,
      they become activated and proliferate to secrete collagen, which results in organ
      fibrosis. An intriguing property of hepatic stellate cells (HSCs) is that they
      undergo apoptosis when collagen is resolved by stopping tissue damage or by
      treatment, even though the mechanisms are unknown. Here we disclose the fact that
      HSCs, normal diploid cells, acquired dependence on collagen for their growth
      during the transition from quiescent to active states. The intramolecular RGD
      motifs of collagen were exposed by cleavage with their own membrane type 1 matrix
      metalloproteinase (MT1-MMP). The following evidence supports this conclusion.
      When rat activated HSCs (aHSCs) were transduced with siRNA against the collagen
      specific chaperone gp46 to inhibit collagen secretion, the cells underwent
      autophagy followed by apoptosis. Concomitantly, the growth of aHSCs was
      suppressed, whereas that of quiescent HSCs was not. These in vitro results are
      compatible with the in vivo observation that apoptosis of aHSCs was induced in
      cirrhotic livers of rats treated with siRNAgp46. siRNA against MT1-MMP and
      addition of tissue inhibitor of metalloproteinase 2 (TIMP-2), which mainly
      inhibits MT1-MMP, also significantly suppressed the growth of aHSCs in vitro. The
      RGD inhibitors echistatin and GRGDS peptide and siRNA against the RGD receptor
      alphaVbeta1 resulted in the inhibition of aHSCs growth. Transduction of siRNAs
      against gp46, alphaVbeta1, and MT1-MMP to aHSCs inhibited the survival signal of
      PI3K/AKT/IkappaB. These results could provide novel antifibrosis strategies. 

PMID- 24867952
TI  - Calcium entry in Toxoplasma gondii and its enhancing effect of invasion-linked
      traits.
AB  - During invasion and egress from their host cells, Apicomplexan parasites face
      sharp changes in the surrounding calcium ion (Ca(2+)) concentration. Our work
      with Toxoplasma gondii provides evidence for Ca(2+) influx from the extracellular
      milieu leading to cytosolic Ca(2+) increase and enhancement of virulence traits,
      such as gliding motility, conoid extrusion, microneme secretion, and host cell
      invasion. Assays of Mn(2+) and Ba(2+) uptake do not support a canonical store
      regulated Ca(2+) entry mechanism. Ca(2+) entry was blocked by the L-type Ca(2+)
      channel inhibitor nifedipine and stimulated by the increase in cytosolic Ca(2+)
      and by the specific L-type Ca(2+) channel agonist Bay K-8644. Our results
      demonstrate that Ca(2+) entry is critical for parasite virulence. We propose a
      regulated Ca(2+) entry mechanism activated by cytosolic Ca(2+) that has an
      enhancing effect on invasion-linked traits. 

PMID- 24867953
TI  - Identification of receptor binding-induced conformational changes in non-visual
      arrestins.
AB  - The non-visual arrestins, arrestin-2 and arrestin-3, belong to a small family of
      multifunctional cytosolic proteins. Non-visual arrestins interact with hundreds
      of G protein-coupled receptors (GPCRs) and regulate GPCR desensitization by
      binding active phosphorylated GPCRs and uncoupling them from heterotrimeric G
      proteins. Recently, non-visual arrestins have been shown to mediate G protein
      independent signaling by serving as adaptors and scaffolds that assemble
      multiprotein complexes. By recruiting various partners, including trafficking and
      signaling proteins, directly to GPCRs, non-visual arrestins connect activated
      receptors to diverse signaling pathways. To investigate arrestin-mediated
      signaling, a structural understanding of arrestin activation and interaction with
      GPCRs is essential. Here we identified global and local conformational changes in
      the non-visual arrestins upon binding to the model GPCR rhodopsin. To detect
      conformational changes, pairs of spin labels were introduced into arrestin-2 and
      arrestin-3, and the interspin distances in the absence and presence of the
      receptor were measured by double electron electron resonance spectroscopy. Our
      data indicate that both non-visual arrestins undergo several conformational
      changes similar to arrestin-1, including the finger loop moving toward the
      predicted location of the receptor in the complex as well as the C-tail release
      upon receptor binding. The arrestin-2 results also suggest that there is no clam
      shell-like closure of the N- and C-domains and that the loop containing residue
      136 (homolog of 139 in arrestin-1) has high flexibility in both free and receptor
      bound states. 

PMID- 24867954
TI  - Structural basis for dimerization and catalysis of a novel esterase from the
      GTSAG motif subfamily of the bacterial hormone-sensitive lipase family.
AB  - Hormone-sensitive lipases (HSLs) are widely distributed in microorganisms,
      plants, and animals. Microbial HSLs are classified into two subfamilies, an
      unnamed new subfamily and the GDSAG motif subfamily. Due to the lack of
      structural information, the detailed catalytic mechanism of the new subfamily is
      not yet clarified. Based on sequence analysis, we propose to name the new
      subfamily as the GTSAG motif subfamily. We identified a novel HSL esterase E25, a
      member of the GTSAG motif subfamily, by functional metagenomic screening, and
      resolved its structure at 2.05 A. E25 is mesophilic (optimum temperature at 50 
      degrees C), salt-tolerant, slightly alkaline (optimum pH at 8.5) for its
      activity, and capable of hydrolyzing short chain monoesters (C2-C10). E25 tends
      to form dimers both in the crystal and in solution. An E25 monomer contains an N
      terminal CAP domain, and a classical alpha/beta hydrolase-fold domain. Residues
      Ser(186), Asp(282), and His(312) comprise the catalytic triad. Structural and
      mutational analyses indicated that E25 adopts a dimerization pattern distinct
      from other HSLs. E25 dimer is mainly stabilized by an N-terminal loop
      intersection from the CAP domains and hydrogen bonds and salt bridges involving
      seven highly conserved hydrophilic residues from the catalytic domains. Further
      analysis indicated that E25 also has some catalytic profiles different from other
      HSLs. Dimerization is essential for E25 to exert its catalytic activity by
      keeping the accurate orientation of the catalytic Asp(282) within the catalytic
      triad. Our results reveal the structural basis for dimerization and catalysis of
      an esterase from the GTSAG motif subfamily of the HSL family. 

PMID- 24867955
TI  - Insulin receptor activation with transmembrane domain ligands.
AB  - Complementary surfaces are buried when peptide hormones, growth factors, or
      cytokines bind and activate cellular receptors. Although these extended surfaces
      provide high affinity and specificity to the interactions, they also present
      great challenges to the design of small molecules that might either mimic or
      antagonize the process. We show that the insulin receptor (IR) and downstream
      signals can be activated by targeting a site outside of its ligand-binding
      domain. A 24-residue peptide having the IR transmembrane (TM) domain sequence
      activates IR, but not related growth factor receptors, through specific
      interactions with the receptor TM domain. Like insulin-dependent activation, IR
      TM requires that IR have a competent ATP-binding site and kinase activation loop.
      IR-TM also activates mutated receptors from patients with severe insulin
      resistance, which do not respond to insulin. These results show that IR can be
      activated through a pathway that bypasses its canonical ligand-binding domain. 

PMID- 24867956
TI  - The mitochondrial protein NLRX1 controls the balance between extrinsic and
      intrinsic apoptosis.
AB  - NLRX1 is a mitochondrial Nod-like receptor (NLR) protein whose function remains
      enigmatic. Here, we observed that NLRX1 expression was glucose-regulated and
      blunted by SV40 transformation. In transformed but not primary murine embryonic
      fibroblasts, NLRX1 expression mediated resistance to an extrinsic apoptotic
      signal, whereas conferring susceptibility to intrinsic apoptotic signals, such as
      glycolysis inhibition, increased cytosolic calcium and endoplasmic reticulum
      stress. In a murine model of colorectal cancer induced by azoxymethane, NLRX1-/-
      mice developed fewer tumors than wild type mice. In contrast, in a colitis
      associated cancer model combining azoxymethane and dextran sulfate sodium, NLRX1
      /- mice developed a more severe pathology likely due to the increased sensitivity
      to dextran sulfate sodium colitis. Together, these results identify NLRX1 as a
      critical mitochondrial protein implicated in the regulation of apoptosis in
      cancer cells. The unique capacity of NLRX1 to regulate the cellular sensitivity
      toward intrinsic versus extrinsic apoptotic signals suggests a critical role for
      this protein in numerous physiological processes and pathological conditions. 

PMID- 24867957
TI  - N-glycosylation is required for matriptase-2 autoactivation and ectodomain
      shedding.
AB  - Matriptase-2 is a hepatic membrane serine protease that regulates iron
      homeostasis. Defects in matriptase-2 cause iron deficiency anemia. In cells,
      matriptase-2 is synthesized as a zymogen. To date, how matriptase-2 expression
      and activation are regulated remains poorly understood. Here we expressed human
      matriptase-2 in HEK293 and hepatic BEL-7402, SMMC-7721, and QGY-7703 cells. By
      labeling cell surface proteins and Western analysis, we examined matriptase-2
      cell surface expression, zymogen activation, and ectodomain shedding. Our results
      show that matriptase-2 was activated on the cell surface but not intracellularly.
      Activated matriptase-2 underwent ectodomain shedding, producing soluble fragments
      in the conditioned medium. By testing inactive mutants, R576A and S762A, we found
      that matriptase-2 activation and shedding were mediated by its own catalytic
      activity and that the one-chain form of matriptase-2 had little activity in
      ectodomain shedding. We made additional matriptase-2 mutants, N136Q, N184Q,
      N216Q, N338Q, N433Q, N453Q, and N518Q, in which each of the predicted N
      glycosylation sites was mutated. All of these mutants were expressed on the cell
      surface. However, mutants N216Q, N453Q, and N518Q, but not the other mutants, had
      impaired zymogen activation and ectodomain shedding. Our results indicate that N
      glycans at specific sites are critical for matriptase-2 activation. Together,
      these data provide new insights into the cell surface expression, zymogen
      activation, and ectodomain shedding of matriptase-2. 

PMID- 24867958
TI  - NHERF2/NHERF3 protein heterodimerization and macrocomplex formation are required
      for the inhibition of NHE3 activity by carbachol.
AB  - NHERF1, NHERF2, and NHERF3 belong to the NHERF (Na(+)/H(+) exchanger regulatory
      factor) family of PSD-95/Discs-large/ZO-1 (PDZ) scaffolding proteins.
      Individually, each NHERF protein has been shown to be involved in the regulation
      of multiple receptors or transporters including Na(+)/H(+) exchanger 3 (NHE3).
      Although NHERF dimerizations have been reported, results have been inconsistent,
      and the physiological function of NHERF dimerizations is still unknown. The
      current study semiquantitatively compared the interaction strength among all
      possible homodimerizations and heterodimerizations of these three NHERF proteins
      by pulldown and co-immunoprecipitation assays. Both methods showed that NHERF2
      and NHERF3 heterodimerize as the strongest interaction among all NHERF
      dimerizations. In vivo NHERF2/NHERF3 heterodimerization was confirmed by FRET and
      FRAP (fluorescence recovery after photobleach). NHERF2/NHERF3 heterodimerization
      is mediated by PDZ domains of NHERF2 and the C-terminal PDZ domain recognition
      motif of NHERF3. The NHERF3-4A mutant is defective in heterodimerization with
      NHERF2 and does not support the inhibition of NHE3 by carbachol. This suggests a
      role for NHERF2/NHERF3 heterodimerization in the regulation of NHE3 activity. In
      addition, both PDZ domains of NHERF2 could be simultaneously occupied by NHERF3
      and another ligand such as NHE3, alpha-actinin-4, and PKCalpha, promoting
      formation of NHE3 macrocomplexes. This study suggests that NHERF2/NHERF3
      heterodimerization mediates the formation of NHE3 macrocomplexes, which are
      required for the inhibition of NHE3 activity by carbachol. 

PMID- 24867960
TI  - Beyond androgen deprivation: ancillary integrative strategies for targeting the
      androgen receptor addiction of prostate cancer.
AB  - The large majority of clinical prostate cancers remain dependent on androgen
      receptor (AR) activity for proliferation even as they lose their responsiveness
      to androgen deprivation or antagonism. AR activity can be maintained in these
      circumstances by increased AR synthesis--often reflecting increased NF-kappaB
      activation; upregulation of signaling pathways that promote AR activity in the
      absence of androgens; and by emergence of AR mutations or splice variants lacking
      the ligand-binding domain, which render the AR constitutively active. Drugs
      targeting the N-terminal transactivating domain of the AR, some of which are now
      in preclinical development, can be expected to inhibit the activity not only of
      unmutated ARs but also of the mutant forms and splice variants selected for by
      androgen deprivation. Concurrent measures that suppress AR synthesis or boost AR
      turnover could be expected to complement the efficacy of such drugs. A number of
      nutraceuticals that show efficacy in prostate cancer xenograft models--including
      polyphenols from pomegranate, grape seed, and green tea, the crucifera metabolite
      diindolylmethane, and the hormone melatonin--have the potential to suppress AR
      synthesis via downregulation of NF-kappaB activity; clinical doses of salicylate
      may have analogous efficacy. The proteasomal turnover of the AR is abetted by
      diets with a high ratio of long-chain omega-3 to omega-6 fatty acids, which are
      beneficial in prostate cancer xenograft models; berberine and sulforaphane, by
      inhibiting AR's interaction with its chaperone Hsp90, likewise promote AR
      proteasomal degradation and retard growth of human prostate cancer in nude mice.
      Hinge region acetylation of the AR is required for optimal transactivational
      activity, and low micromolar concentrations of the catechin epigallocatechin-3
      gallate (EGCG) can inhibit such acetylation--possibly explaining the ability of
      EGCG administration to suppress androgenic activity and cell proliferation in
      prostate cancer xenografts. Hence, it is proposed that regimens featuring an N
      terminal domain-targeting drug, various nutraceuticals/drugs that downregulate NF
      kappaB activity, and/or supplemental intakes of fish oil, berberine,
      sulforaphane, and EGCG have potential for blocking proliferation of prostate
      cancer by targeting its characteristic addiction to androgen receptor activity.

PMID- 24867961
TI  - Intravenous Vitamin C and Cancer: A Systematic Review.
AB  - BACKGROUND: Intravenous vitamin C (IVC) is a contentious adjunctive cancer
      therapy, widely used in naturopathic and integrative oncology settings. We
      conducted a systematic review of human interventional and observational studies
      assessing IVC for use in cancer patients. METHODS: We searched MEDLINE, EMBASE,
      The Cochrane Library, CINAHL, and AMED from inception to April 2013 for human
      studies examining the safety, effectiveness, or pharmacokinetics of IVC use in
      cancer patients. RESULTS: Of 897 records, a total of 39 reports of 37 studies
      were included: 2 randomized controlled trials (RCTs), 15 uncontrolled trials, 6
      observational studies, and 14 case reports. IVC dosing ranged from 1 g to more
      than 200 g ascorbic acid per infusion, typically administered 2 to 3 times
      weekly. IVC does not appear to increase toxicity or interfere with antitumor
      effects of gemcitabine/erlotinib therapy or paclitaxel and carboplatin. Based on
      1 RCT and data from uncontrolled human trials, IVC may improve time to relapse
      and possibly enhance reductions in tumor mass and improve survival in combination
      with chemotherapy. IVC may improve quality of life, physical function, and
      toxicities associated with chemotherapy, including fatigue, nausea, insomnia,
      constipation, and depression. Case reports document several instances of tumor
      regression and long-term disease-free survival associated with use of IVC.
      CONCLUSION: There is limited high-quality clinical evidence on the safety and
      effectiveness of IVC. The existing evidence is preliminary and cannot be
      considered conclusive but is suggestive of a good safety profile and potentially
      important antitumor activity; however, more rigorous evidence is needed to
      conclusively demonstrate these effects. IVC may improve the quality of life and
      symptom severity of patients with cancer, and several cases of cancer remission
      have been reported. Well-designed, controlled studies of IVC therapy are needed.

PMID- 24867959
TI  - A pilot study of acupuncture in treating bortezomib-induced peripheral neuropathy
      in patients with multiple myeloma.
AB  - BACKGROUND: Peripheral neuropathy is the dose limiting toxicity of bortezomib in
      patients with multiple myeloma (MM). OBJECTIVES: To examine the safety,
      feasibility and efficacy of acupuncture in reducing bortezomib-induced peripheral
      neuropathy (BIPN) symptoms. METHODS: Patients with MM experiencing persistent
      BIPN >=grade 2 despite adequate medical intervention and discontinuation of
      bortezomib received 10 acupuncture treatments for 10 weeks (2*/week for 2 weeks,
      1*/week for 4 weeks, and then biweekly for 4 weeks). Responses were assessed by
      the Clinical Total Neuropathy Score (TNSc), Functional Assessment of Cancer
      Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) questionnaire,
      and the Neuropathy Pain Scale (NPS). Repeated-measures analysis of variance was
      used to test for monotonic decline in scores on each of the measures. Serial
      serum levels of proinflammatory and neurotrophic cytokines were obtained at
      baseline and weeks 1, 2, 4, 8, and 14. RESULTS: Twenty-seven patients with MM
      were enrolled in the trial. There were no adverse events associated with the
      acupuncture treatments. TNSc data were deemed invalid and therefore were not
      reported. At weeks 10 and 14, FACT/GOG-Ntx and NPS showed significant reduction
      suggesting decreased pain, and improved function (P values were <.0001 for both
      FACT/GOG-Ntx and NPS at weeks 10 and 14). However, nerve conduction studies did
      not significantly change between baseline assessment and end of study. There was
      no correlation in serum cytokines for responders versus none responders.
      CONCLUSIONS: Acupuncture is safe, feasible and produces subjective improvements
      in patients' symptoms. A follow-up randomized controlled trial is warranted.

PMID- 24867962
TI  - Gastrointestinal colonization with a cephalosporinase-producing bacteroides
      species preserves colonization resistance against vancomycin-resistant
      enterococcus and Clostridium difficile in cephalosporin-treated mice.
AB  - Antibiotics that are excreted into the intestinal tract may disrupt the
      indigenous intestinal microbiota and promote colonization by health care
      associated pathogens. beta-Lactam, or penicillin-type, antibiotics are among the
      most widely utilized antibiotics worldwide and may also adversely affect the
      microbiota. Many bacteria are capable, however, of producing beta-lactamase
      enzymes that inactivate beta-lactam antibiotics. We hypothesized that prior
      establishment of intestinal colonization with a beta-lactamase-producing anaerobe
      might prevent these adverse effects of beta-lactam antibiotics, by inactivating
      the portion of antibiotic that is excreted into the intestinal tract. Here, mice
      with a previously abolished microbiota received either oral normal saline or an
      oral cephalosporinase-producing strain of Bacteroides thetaiotaomicron for 3
      days. Mice then received 3 days of subcutaneous ceftriaxone, followed by either
      oral administration of vancomycin-resistant Enterococcus (VRE) or sacrifice and
      assessment of in vitro growth of epidemic and nonepidemic strains of Clostridium
      difficile in murine cecal contents. Stool concentrations of VRE and ceftriaxone
      were measured, cecal levels of C. difficile 24 h after incubation were
      quantified, and denaturing gradient gel electrophoresis (DGGE) of microbial 16S
      rRNA genes was performed to evaluate the antibiotic effect on the microbiota. The
      results demonstrated that establishment of prior colonization with a beta
      lactamase-producing intestinal anaerobe inactivated intraintestinal ceftriaxone
      during treatment with this antibiotic, allowed recovery of the normal microbiota
      despite systemic ceftriaxone, and prevented overgrowth with VRE and epidemic and
      nonepidemic strains of C. difficile in mice. These findings describe a novel
      probiotic strategy to potentially prevent pathogen colonization in hospitalized
      patients. 

PMID- 24867963
TI  - Bordetella pertussis lipid A glucosamine modification confers resistance to
      cationic antimicrobial peptides and increases resistance to outer membrane
      perturbation.
AB  - Bordetella pertussis, the causative agent of whooping cough, has many strategies
      for evading the human immune system. Lipopolysaccharide (LPS) is an important
      Gram-negative bacterial surface structure that activates the immune system via
      Toll-like receptor 4 and enables susceptibility to cationic antimicrobial
      peptides (CAMPs). We show modification of the lipid A region of LPS with
      glucosamine increased resistance to numerous CAMPs, including LL-37. Furthermore,
      we demonstrate that this glucosamine modification increased resistance to outer
      membrane perturbation. 

PMID- 24867964
TI  - Whole-genome analyses of Enterococcus faecium isolates with diverse daptomycin
      MICs.
AB  - Daptomycin (DAP) is a lipopeptide antibiotic frequently used as a "last-resort"
      antibiotic against vancomycin-resistant Enterococcus faecium (VRE). However, an
      important limitation for DAP therapy against VRE is the emergence of resistance
      during therapy. Mutations in regulatory systems involved in cell envelope
      homeostasis are postulated to be important mediators of DAP resistance in E.
      faecium. Thus, in order to gain insights into the genetic bases of DAP resistance
      in E. faecium, we investigated the presence of changes in 43 predicted proteins
      previously associated with DAP resistance in enterococci and staphylococci using
      the genomes of 19 E. faecium with different DAP MICs (range, 3 to 48 MUg/ml).
      Bodipy-DAP (BDP-DAP) binding to the cell membrane assays and time-kill curves
      (DAP alone and with ampicillin) were performed. Genetic changes involving two
      major pathways were identified: (i) LiaFSR, a regulatory system associated with
      the cell envelope stress response, and (ii) YycFGHIJ, a system involved in the
      regulation of cell wall homeostasis. Thr120 -> Ala and Trp73 -> Cys substitutions
      in LiaS and LiaR, respectively, were the most common changes identified. DAP
      bactericidal activity was abolished in the presence of liaFSR or yycFGHIJ
      mutations regardless of the DAP MIC and was restored in the presence of
      ampicillin, but only in representatives of the LiaFSR pathway. Reduced binding of
      BDP-DAP to the cell surface was the predominant finding correlating with
      resistance in isolates with DAP MICs above the susceptibility breakpoint. Our
      findings suggest that genotypic information may be crucial to predict response to
      DAP plus beta-lactam combinations and continue to question the DAP breakpoint of
      4 MUg/ml.

PMID- 24867965
TI  - New amphiphilic neamine derivatives active against resistant Pseudomonas
      aeruginosa and their interactions with lipopolysaccharides.
AB  - The development of novel antimicrobial agents is urgently required to curb the
      widespread emergence of multidrug-resistant bacteria like colistin-resistant
      Pseudomonas aeruginosa. We previously synthesized a series of amphiphilic neamine
      derivatives active against bacterial membranes, among which 3',6-di-O-[(2"
      naphthyl)propyl]neamine (3',6-di2NP), 3',6-di-O-[(2"-naphthyl)butyl]neamine (3',6
      di2NB), and 3',6-di-O-nonylneamine (3',6-diNn) showed high levels of activity and
      low levels of cytotoxicity (L. Zimmermann et al., J. Med. Chem. 56:7691-7705,
      2013). We have now further characterized the activity of these derivatives
      against colistin-resistant P. aeruginosa and studied their mode of action;
      specifically, we characterized their ability to interact with lipopolysaccharide
      (LPS) and to alter the bacterial outer membrane (OM). The three amphiphilic
      neamine derivatives were active against clinical colistin-resistant strains
      (MICs, about 2 to 8 MUg/ml), The most active one (3',6-diNn) was bactericidal at
      its MIC and inhibited biofilm formation at 2-fold its MIC. They cooperatively
      bound to LPSs, increasing the outer membrane permeability. Grafting long and
      linear alkyl chains (nonyl) optimized binding to LPS and outer membrane
      permeabilization. The effects of amphiphilic neamine derivatives on LPS micelles
      suggest changes in the cross-bridging of lipopolysaccharides and disordering in
      the hydrophobic core of the micelles. The molecular shape of the 3',6-dialkyl
      neamine derivatives induced by the nature of the grafted hydrophobic moieties
      (naphthylalkyl instead of alkyl) and the flexibility of the hydrophobic moiety
      are critical for their fluidifying effect and their ability to displace cations
      bridging LPS. Results from this work could be exploited for the development of
      new amphiphilic neamine derivatives active against colistin-resistant P.
      aeruginosa.

PMID- 24867966
TI  - Effects of the W153L substitution in HIV reverse transcriptase on viral
      replication and drug resistance to multiple categories of reverse transcriptase
      inhibitors.
AB  - A W153L substitution in HIV-1 reverse transcriptase (RT) was recently identified
      by selection with a novel nucleotide-competing RT inhibitor (NcRTI) termed
      compound A that is a member of the benzo[4,5]furo[3,2,d]pyrimidin-2-one NcRTI
      family of drugs. To investigate the impact of W153L, alone or in combination with
      the clinically relevant RT resistance substitutions K65R (change of Lys to Arg at
      position 65), M184I, K101E, K103N, E138K, and Y181C, on HIV-1 phenotypic
      susceptibility, viral replication, and RT enzymatic function, we generated
      recombinant RT enzymes and viruses containing each of these substitutions or
      various combinations of them. We found that W153L-containing viruses were
      impaired in viral replicative capacity and were hypersusceptible to tenofovir
      (TFV) while retaining susceptibility to most nonnucleoside RT inhibitors. The
      nucleoside 3TC retained potency against W153L-containing viruses but not when the
      M184I substitution was also present. W153L was also able to reverse the effects
      of the K65R substitution on resistance to TFV, and K65R conferred
      hypersusceptibility to compound A. Biochemical assays demonstrated that W153L
      alone or in combination with K65R, M184I, K101E, K103N, E138K, and Y181C impaired
      enzyme processivity and polymerization efficiency but did not diminish RNase H
      activity, providing mechanistic insights into the low replicative fitness
      associated with these substitutions. We show that the mechanism of the TFV
      hypersusceptibility conferred by W153L is mainly due to increased efficiency of
      TFV-diphosphate incorporation. These results demonstrate that compound A and/or
      derivatives thereof have the potential to be important antiretroviral agents that
      may be combined with tenofovir to achieve synergistic results. 

PMID- 24867968
TI  - In vitro and in vivo assessment of dermatophyte acquired resistance to
      efinaconazole, a novel triazole antifungal.
AB  - Efinaconazole is a novel triazole antifungal drug for the topical treatment of
      onychomycosis, a nail infection caused mainly by dermatophytes. We assessed the
      potential of efinaconazole to induce resistance in dermatophytes by continuous
      exposure of Trichophyton rubrum strains to efinaconazole in vitro (12 passages)
      and in a guinea pig onychomycosis model (8 weeks). There was no evidence of
      efinaconazole resistance development in the tested strains under the experimental
      conditions used. 

PMID- 24867967
TI  - Emergence of resistance to atovaquone-proguanil in malaria parasites: insights
      from computational modeling and clinical case reports.
AB  - The usefulness of atovaquone-proguanil (AP) as an antimalarial treatment is
      compromised by the emergence of atovaquone resistance during therapy. However,
      the origin of the parasite mitochondrial DNA (mtDNA) mutation conferring
      atovaquone resistance remains elusive. Here, we report a patient-based stochastic
      model that tracks the intrahost emergence of mutations in the multicopy mtDNA
      during the first erythrocytic parasite cycles leading to the malaria febrile
      episode. The effect of mtDNA copy number, mutation rate, mutation cost, and total
      parasite load on the mutant parasite load per patient was evaluated. Computer
      simulations showed that almost any infected patient carried, after four to seven
      erythrocytic cycles, de novo mutant parasites at low frequency, with varied
      frequencies of parasites carrying varied numbers of mutant mtDNA copies. A large
      interpatient variability in the size of this mutant reservoir was found; this
      variability was due to the different parameters tested but also to the relaxed
      replication and partitioning of mtDNA copies during mitosis. We also report seven
      clinical cases in which AP-resistant infections were treated by AP. These
      provided evidence that parasiticidal drug concentrations against AP-resistant
      parasites were transiently obtained within days after treatment initiation.
      Altogether, these results suggest that each patient carries new mtDNA mutant
      parasites that emerge before treatment but are killed by high starting drug
      concentrations. However, because the size of this mutant reservoir is highly
      variable from patient to patient, we propose that some patients fail to eliminate
      all of the mutant parasites, repeatedly producing de novo AP treatment failures. 

PMID- 24867969
TI  - Interspecies mixed-effect pharmacokinetic modeling of penicillin G in cattle and
      swine.
AB  - Extralabel drug use of penicillin G in food-producing animals may cause an excess
      of residues in tissue which will have the potential to damage human health. Of
      all the antibiotics, penicillin G may have the greatest potential for producing
      allergic responses to the consumer of food animal products. There are, however,
      no population pharmacokinetic studies of penicillin G for food animals. The
      objective of this study was to develop a population pharmacokinetic model to
      describe the time-concentration data profile of penicillin G across two species.
      Data were collected from previously published pharmacokinetic studies in which
      several formulations of penicillin G were administered to diverse populations of
      cattle and swine. Liver, kidney, and muscle residue data were also used in this
      study. Compartmental models with first-order absorption and elimination were fit
      to plasma and tissue concentrations using a nonlinear mixed-effect modeling
      approach. A 3-compartment model with extra tissue compartments was selected to
      describe the pharmacokinetics of penicillin G. Typical population parameter
      estimates (interindividual variability) were central volumes of distribution of
      3.45 liters (12%) and 3.05 liters (8.8%) and central clearance of 105 liters/h
      (32%) and 16.9 liters/h (14%) for cattle and swine, respectively, with peripheral
      clearance of 24.8 liters/h (13%) and 9.65 liters/h (23%) for cattle and 13.7
      liters/h (85%) and 0.52 liters/h (40%) for swine. Body weight and age were the
      covariates in the final pharmacokinetic models. This study established a robust
      model of penicillin for a large and diverse population of food-producing animals
      which could be applied to other antibiotics and species in future analyses. 

PMID- 24867970
TI  - In vitro and in vivo evidence for amphotericin B as a P-glycoprotein substrate on
      the blood-brain barrier.
AB  - Amphotericin B (AMB) has been a mainstay therapy for fungal infections of the
      central nervous system, but its use has been limited by its poor penetration into
      the brain, the mechanism of which remains unclear. In this study, we aimed to
      investigate the role of P-glycoprotein (P-gp) in AMB crossing the blood-brain
      barrier (BBB). The uptake of AMB by primary brain capillary endothelial cells in
      vitro was significantly enhanced after inhibition of P-gp by verapamil. The
      impact of two model P-gp inhibitors, verapamil and itraconazole, on brain/plasma
      ratios of AMB was examined in both uninfected CD-1 mice and those intracerebrally
      infected with Cryptococcus neoformans. In uninfected mice, the brain/plasma
      ratios of AMB were increased 15 min (3.5 versus 2.0; P < 0.05) and 30 min (5.2
      versus 2.8; P < 0.05) after administration of verapamil or 45 min (6.0 versus
      3.9; P < 0.05) and 60 min (5.4 versus 3.8; P < 0.05) after itraconazole
      administration. The increases in brain/plasma ratios were also observed in
      infected mice treated with AMB and P-gp inhibitors. The brain tissue fungal CFU
      in infected mice were significantly lower in AMB-plus-itraconazole or verapamil
      groups than in the untreated group (P < 0.005), but none of the treatments
      protected the mice from succumbing to the infection. In conclusion, we
      demonstrated that P-gp inhibitors can enhance the uptake of AMB through the BBB,
      suggesting that AMB is a P-gp substrate. 

PMID- 24867971
TI  - Deletion of the uracil permease gene confers cross-resistance to 5-fluorouracil
      and azoles in Candida lusitaniae and highlights antagonistic interaction between
      fluorinated nucleotides and fluconazole.
AB  - We characterized two additional membrane transporters (Fur4p and Dal4p) of the
      nucleobase cation symporter 1 (NCS1) family involved in the uptake transport of
      pyrimidines and related molecules in the opportunistic pathogenic yeast Candida
      lusitaniae. Simple and multiple null mutants were constructed by gene deletion
      and genetic crosses. The function of each transporter was characterized by
      supplementation experiments, and the kinetic parameters of the uptake transport
      of uracil were measured using radiolabeled substrate. Fur4p specifically
      transports uracil and 5-fluorouracil. Dal4p is very close to Fur4p and transports
      allantoin (glyoxyldiureide). Deletion of the FUR4 gene confers resistance to 5
      fluorouracil as well as cross-resistance to triazoles and imidazole antifungals
      when they are used simultaneously with 5-fluorouracil. However, the nucleobase
      transporters are not involved in azole uptake. Only fluorinated pyrimidines, not
      pyrimidines themselves, are able to promote cross-resistance to azoles by both
      the salvage and the de novo pathway of pyrimidine synthesis. A reinterpretation
      of the data previously obtained led us to show that subinhibitory doses of 5
      fluorocytosine, 5-fluorouracil, and 5-fluorouridine also were able to trigger
      resistance to fluconazole in susceptible wild-type strains of C. lusitaniae and
      of different Candida species. Our results suggest that intracellular fluorinated
      nucleotides play a key role in azole resistance, either by preventing azoles from
      targeting the lanosterol 14-alpha-demethylase or its catalytic site or by acting
      as a molecular switch for the triggering of efflux transport. 

PMID- 24867972
TI  - Association between pncA gene mutations, pyrazinamidase activity, and
      pyrazinamide susceptibility testing in Mycobacterium tuberculosis.
AB  - We determined MICs for, confirmed the presence of pncA mutations in, and
      performed pyrazinamidase testing on colonies (subclones) obtained from seven
      isolates that exhibited differential pyrazinamide (PZA) susceptibility. Six of
      the seven strains were found to exhibit characteristics resulting from the
      mixture of strains possessing different properties. In addition, our analysis
      revealed large pncA-spanning deletions (1,565 bp, 4,475 bp, and 6,258 bp) in
      three strains that showed high PZA resistance. 

PMID- 24867974
TI  - Decreased ceftriaxone susceptibility in emerging (35B and 6C) and persisting
      (19A) Streptococcus pneumoniae serotypes in the United States, 2011-2012:
      ceftaroline remains active in vitro among beta-lactam agents.
AB  - Totals of 8.7% (103/1,190) and 21.0% (249/1,190) of the Streptococcus pneumoniae
      isolates recovered from specimens collected in the United States during the 2011
      2012 AWARE (Assessing Worldwide Antimicrobial Resistance Evaluation) Surveillance
      Program were ceftriaxone nonsusceptible according to the CLSI (<= 1 MUg/ml for
      susceptible) and EUCAST (<= 0.5 MUg/ml for susceptible) criteria, respectively.
      Decreased susceptibility to ceftriaxone (MIC, 1 MUg/ml) was frequently observed
      among serotypes 19 A (51.4%; 128/249) and 35 B (29.7%; 74/249), which were most
      often observed in the East South Central and South Atlantic U.S. Census regions.
      Ceftaroline (MIC50/90, 0.12/0.25 MUg/ml) remained active (>= 96.8% susceptible)
      when tested against these less susceptible isolates.

PMID- 24867973
TI  - SAMHD1 has differential impact on the efficacies of HIV nucleoside reverse
      transcriptase inhibitors.
AB  - Sterile alpha motif- and histidine/aspartic acid domain-containing protein 1
      (SAMHD1) limits HIV-1 replication by hydrolyzing deoxynucleoside triphosphates
      (dNTPs) necessary for reverse transcription. Nucleoside reverse transcriptase
      inhibitors (NRTIs) are components of anti-HIV therapies. We report here that
      SAMHD1 cleaves NRTI triphosphates (TPs) at significantly lower rates than dNTPs
      and that SAMHD1 depletion from monocytic cells affects the susceptibility of HIV
      1 infections to NRTIs in complex ways that depend not only on the relative
      changes in dNTP and NRTI-TP concentrations but also on the NRTI activation
      pathways. 

PMID- 24867975
TI  - Extended-Infusion versus standard-infusion piperacillin-tazobactam for sepsis
      syndromes at a tertiary medical center.
AB  - Piperacillin-tazobactam (PTZ) is frequently used as empirical and targeted
      therapy for Gram-negative sepsis. Time-dependent killing properties of PTZ
      support the use of extended-infusion (EI) dosing; however, studies have shown
      inconsistent benefits of EI PTZ treatment on clinical outcomes. We performed a
      retrospective cohort study of adult patients who received EI PTZ treatment and
      historical controls who received standard-infusion (SI) PTZ treatment for
      presumed sepsis syndromes. Data on mortality rates, clinical outcomes, length of
      stay (LOS), and disease severity were obtained. A total of 843 patients (662 with
      EI treatment and 181 with SI treatment) were available for analysis. Baseline
      characteristics of the two groups were similar, except for fewer female patients
      receiving EI treatment. No significant differences between the EI and SI groups
      in inpatient mortality rates (10.9% versus 13.8%; P = 0.282), overall LOS (10
      versus 12 days; P = 0.171), intensive care unit (ICU) LOS (7 versus 6 days; P =
      0.061), or clinical failure rates (18.4% versus 19.9%; P = 0.756) were observed.
      However, the duration of PTZ therapy was shorter in the EI group (5 versus 6
      days; P < 0.001). Among ICU patients, no significant differences in outcomes
      between the EI and SI groups were observed. Patients with urinary or intra
      abdominal infections had lower mortality and clinical failure rates when
      receiving EI PTZ treatment. We did not observe significant differences in
      inpatient mortality rates, overall LOS, ICU LOS, or clinical failure rates
      between patients receiving EI PTZ treatment and patients receiving SI PTZ
      treatment. Patients receiving EI PTZ treatment had a shorter duration of PTZ
      therapy than did patients receiving SI treatment, and EI dosing may provide cost
      savings to hospitals. 

PMID- 24867976
TI  - Flow cytometry-based analysis of artemisinin-resistant Plasmodium falciparum in
      the ring-stage survival assay.
AB  - The ring-stage survival assay (RSA) is a powerful tool for phenotyping
      artemisinin-resistant Plasmodium falciparum but requires experienced
      microscopists to count viable parasites among 10,000 erythrocytes in Giemsa
      stained thin blood smears. Here we describe a rapid flow cytometric assay that
      accurately counts viable parasites among 250,000 erythrocytes in suspension. This
      method performs as well as light microscopy and can be used to standardize the
      collection of RSA data between research groups in laboratory and field settings. 

PMID- 24867977
TI  - Plasmodium falciparum founder populations in western Cambodia have reduced
      artemisinin sensitivity in vitro.
AB  - Reduced Plasmodium falciparum sensitivity to short-course artemisinin (ART)
      monotherapy manifests as a long parasite clearance half-life. We recently defined
      three parasite founder populations with long half-lives in Pursat, western
      Cambodia, where reduced ART sensitivity is prevalent. Using the ring-stage
      survival assay, we show that these founder populations have reduced ART
      sensitivity in vitro at the early ring stage of parasite development and that a
      genetically admixed population contains subsets of parasites with normal or
      reduced ART sensitivity. 

PMID- 24867979
TI  - Antifungal resistance to fluconazole and echinocandins is not emerging in yeast
      isolates causing fungemia in a Spanish tertiary care center.
AB  - Accurate knowledge of fungemia epidemiology requires identification of strains to
      the molecular level. Various studies have shown that the rate of resistance to
      fluconazole ranges from 2.5% to 9% in Candida spp. isolated from blood samples.
      However, trends in antifungal resistance have received little attention and have
      been studied only using CLSI M27-A3 methodology. We assessed the fungemia
      epidemiology in a large tertiary care institution in Madrid, Spain, by
      identifying isolates to the molecular level and performing antifungal
      susceptibility testing according to the updated breakpoints of European Committee
      for Antimicrobial Susceptibility Testing (EUCAST) definitive document (EDef) 7.2.
      We studied 613 isolates causing 598 episodes of fungemia in 544 patients admitted
      to our hospital (January 2007 to December 2013). Strains were identified after
      amplification and sequencing of the ITS1-5.8S-ITS2 region and further tested for
      in vitro susceptibility to amphotericin B, fluconazole, posaconazole,
      voriconazole, micafungin, and anidulafungin. Resistance was defined using EUCAST
      species-specific breakpoints, and epidemiological cutoff values (ECOFFs) were
      applied as tentative breakpoints. Most episodes were caused by Candida albicans
      (46%), Candida parapsilosis (28.7%), Candida glabrata (9.8%), and Candida
      tropicalis (8%). Molecular identification enabled us to better detect cryptic
      species of Candida guilliermondii and C. parapsilosis complexes and episodes of
      polyfungal fungemia. The overall percentage of fluconazole-resistant isolates was
      5%, although it was higher in C. glabrata (8.6%) and non-Candida yeast isolates
      (47.4%). The rate of resistance to echinocandins was 4.4% and was mainly due to
      the presence of intrinsically resistant non-Candida species. Resistance mainly
      affected non-Candida yeasts. The rate of resistance to fluconazole and
      echinocandins did not change considerably during the study period. 

PMID- 24867978
TI  - In vitro and in vivo evaluation of 28DAP010, a novel diamidine for treatment of
      second-stage African sleeping sickness.
AB  - African sleeping sickness is a neglected tropical disease transmitted by tsetse
      flies. New and better drugs are still needed especially for its second stage,
      which is fatal if untreated. 28DAP010, a dipyridylbenzene analogue of DB829, is
      the second simple diamidine found to cure mice with central nervous system
      infections by a parenteral route of administration. 28DAP010 showed efficacy
      similar to that of DB829 in dose-response studies in mouse models of first- and
      second-stage African sleeping sickness. The in vitro time to kill, determined by
      microcalorimetry, and the parasite clearance time in mice were shorter for
      28DAP010 than for DB829. No cross-resistance was observed between 28DAP010 and
      pentamidine on the tested Trypanosoma brucei gambiense isolates from melarsoprol
      refractory patients. 28DAP010 is the second promising preclinical candidate among
      the diamidines for the treatment of second-stage African sleeping sickness. 

PMID- 24867982
TI  - Novel multiple mutations in the topoisomerase gene of Haitian variant Vibrio
      cholerae O1.

PMID- 24867981
TI  - Selective pharmacologic inhibition of a PASTA kinase increases Listeria
      monocytogenes susceptibility to beta-lactam antibiotics.
AB  - While beta-lactam antibiotics are a critical part of the antimicrobial arsenal,
      they are frequently compromised by various resistance mechanisms, including
      changes in penicillin binding proteins of the bacterial cell wall. Genetic
      deletion of the penicillin binding protein and serine/threonine kinase-associated
      protein (PASTA) kinase in methicillin-resistant Staphylococcus aureus (MRSA) has
      been shown to restore beta-lactam susceptibility. However, the mechanism remains
      unclear, and whether pharmacologic inhibition would have the same effect is
      unknown. In this study, we found that deletion or pharmacologic inhibition of the
      PASTA kinase in Listeria monocytogenes by the nonselective kinase inhibitor
      staurosporine results in enhanced susceptibility to both aminopenicillin and
      cephalosporin antibiotics. Resistance to vancomycin, another class of cell wall
      synthesis inhibitors, or antibiotics that inhibit protein synthesis was
      unaffected by staurosporine treatment. Phosphorylation assays with purified
      kinases revealed that staurosporine selectively inhibited the PASTA kinase of L.
      monocytogenes (PrkA). Importantly, staurosporine did not inhibit a L.
      monocytogenes kinase without a PASTA domain (Lmo0618) or the PASTA kinase from
      MRSA (Stk1). Finally, inhibition of PrkA with a more selective kinase inhibitor,
      AZD5438, similarly led to sensitization of L. monocytogenes to beta-lactam
      antibiotics. Overall, these results suggest that pharmacologic targeting of PASTA
      kinases can increase the efficacy of beta-lactam antibiotics. 

PMID- 24867980
TI  - UPC2A is required for high-level azole antifungal resistance in Candida glabrata.
AB  - Candida glabrata, the second most common cause of Candida infections, is
      associated with high rates of mortality and often exhibits resistance to the
      azole class of antifungal agents. Upc2 and Ecm22 in Saccharomyces cerevisiae and
      Upc2 in Candida albicans are the transcriptional regulators of ERG11, the gene
      encoding the target of azoles in the ergosterol biosynthesis pathway. Recently
      two homologs for these transcription factors, UPC2A and UPC2B, were identified in
      C. glabrata. One of these, UPC2A, was shown to influence azole susceptibility. We
      hypothesized that due to the global role for Upc2 in sterol biosynthesis in S.
      cerevisiae and C. albicans, disruption of UPC2A would enhance the activity of
      fluconazole in both azole-susceptible dose-dependent (SDD) and -resistant C.
      glabrata clinical isolates. To test this hypothesis, we constructed mutants with
      disruptions in UPC2A and UPC2B alone and in combination in a matched pair of
      clinical azole-SDD and -resistant isolates. Disruption of UPC2A in both the SDD
      and resistant isolates resulted in increased susceptibility to sterol
      biosynthesis inhibitors, including a reduction in fluconazole MIC and minimum
      fungicidal concentration, enhanced azole activity by time-kill analysis, a
      decrease in ergosterol content, and downregulation of baseline and inducible
      expression of several sterol biosynthesis genes. Our results indicate that Upc2A
      is a key regulator of ergosterol biosynthesis and is essential for resistance to
      sterol biosynthesis inhibitors in C. glabrata. Therefore, the UPC2A pathway may
      represent a potential cotherapeutic target for enhancing azole activity against
      this organism. 

PMID- 24867983
TI  - In vitro activity and resistance profile of samatasvir, a novel NS5A replication
      inhibitor of hepatitis C virus.
AB  - The hepatitis C virus (HCV) nonstructural 5A (NS5A) protein is a clinically
      validated target for drugs designed to treat chronic HCV infection. This study
      evaluated the in vitro activity, selectivity, and resistance profile of a novel
      anti-HCV compound, samatasvir (IDX719), alone and in combination with other
      antiviral agents. Samatasvir was effective and selective against infectious HCV
      and replicons, with 50% effective concentrations (EC50s) falling within a tight
      range of 2 to 24 pM in genotype 1 through 5 replicons and with a 10-fold EC50
      shift in the presence of 40% human serum in the genotype 1b replicon. The
      EC90/EC50 ratio was low (2.6). A 50% cytotoxic concentration (CC50) of >100 MUM
      provided a selectivity index of >5 * 10(7). Resistance selection experiments
      (with genotype 1a replicons) and testing against replicons bearing site-directed
      mutations (with genotype 1a and 1b replicons) identified NS5A amino acids 28, 30,
      31, 32, and 93 as potential resistance loci, suggesting that samatasvir affects
      NS5A function. Samatasvir demonstrated an overall additive effect when combined
      with interferon alfa (IFN-alpha), ribavirin, representative HCV protease, and
      nonnucleoside polymerase inhibitors or the nucleotide prodrug IDX184. Samatasvir
      retained full activity in the presence of HIV and hepatitis B virus (HBV)
      antivirals and was not cross-resistant with HCV protease, nucleotide, and
      nonnucleoside polymerase inhibitor classes. Thus, samatasvir is a selective low
      picomolar inhibitor of HCV replication in vitro and is a promising candidate for
      future combination therapies with other direct-acting antiviral drugs in HCV
      infected patients. 

PMID- 24867984
TI  - Different interaction profiles of direct-acting anti-hepatitis C virus agents
      with human organic anion transporting polypeptides.
AB  - Simeprevir (SMV), asunaprevir (ASV), daclatasvir (DCV), and sofosbuvir (SFV),
      which are newly developed direct-acting antiviral agents (DAAs) against hepatitis
      C virus (HCV) infection, are among the key components of anti-HCV regimens.
      Preclinical studies have identified inhibitory properties for some of these DAAs
      against organic anion transporting polypeptide 1B (OATP1B) functions. However,
      their details remain mostly uncharacterized. Because OATP1B1 and OATP1B3 play
      determinant roles in the pharmacokinetics of various drugs via their uptake into
      human hepatocytes, it is plausible that the inhibition of these OATP1Bs by a DAA
      would create a potential risk of drug-drug interaction, which has been an
      emerging concern in anti-HCV therapy. Accordingly, in the present study, we
      intended to clarify the inhibitory characteristics of newly developed DAAs toward
      OATP1B1 and -1B3 functions. The results of our coincubation inhibition assays
      have shown that all tested DAAs could inhibit OATP1B1 functions and that SMV,
      ASV, and DCV (to a lesser extent), but not SFV, exhibited long-lasting
      preincubation inhibitory effects on OATP1B1 functions. It was also found that the
      preincubation inhibitory effects of SMV and ASV could augment their coincubation
      inhibition potency. Furthermore, significant, but differential, inhibitory
      effects of the DAAs on the OATP1B3 function were identified. To summarize, our
      results clearly show that the newly developed DAAs are newly identified OATP1B1
      and OATP1B3 inhibitors with distinctive interaction properties. It is believed
      that these inhibition profiles will provide essential information to all
      concerned parties with respect to the clinical significance of DAA-mediated
      inhibition of OATP1Bs in anti-HCV therapy. 

PMID- 24867985
TI  - A new clone sweeps clean: the enigmatic emergence of Escherichia coli sequence
      type 131.
AB  - Escherichia coli sequence type 131 (ST131) is an extensively antimicrobial
      resistant E. coli clonal group that has spread explosively throughout the world.
      Recent molecular epidemiologic and whole-genome phylogenetic studies have
      elucidated the fine clonal structure of ST131, which comprises multiple ST131
      subclones with distinctive resistance profiles, including the (nested) H30, H30
      R, and H30-Rx subclones. The most prevalent ST131 subclone, H30, arose from a
      single common fluoroquinolone (FQ)-susceptible ancestor containing allele 30 of
      fimH (type 1 fimbrial adhesin gene). An early H30 subclone member acquired FQ
      resistance and launched the rapid expansion of the resulting FQ-resistant
      subclone, H30-R. Subsequently, a member of H30-R acquired the CTX-M-15 extended
      spectrum beta-lactamase and launched the rapid expansion of the CTX-M-15
      containing subclone within H30-R, H30-Rx. Clonal expansion clearly is now the
      dominant mechanism for the rising prevalence of both FQ resistance and CTX-M-15
      production in ST131 and in E. coli generally. Reasons for the successful
      dissemination and expansion of the key ST131 subclones remain undefined but may
      include increased transmissibility, greater ability to colonize and/or persist in
      the intestine or urinary tract, enhanced virulence, and more-extensive
      antimicrobial resistance compared to other E. coli. Here we discuss the
      epidemiology and molecular phylogeny of ST131 and its key subclones, possible
      mechanisms for their ecological success, implications of their widespread
      dissemination, and future research needs. 

PMID- 24867986
TI  - Population pharmacokinetics and clinical response for artemether-lumefantrine in
      pregnant and nonpregnant women with uncomplicated Plasmodium falciparum malaria
      in Tanzania.
AB  - Artemether-lumefantrine (AL) is the first-line treatment for uncomplicated
      malaria in the second and third trimesters of pregnancy. Its efficacy during
      pregnancy has recently been challenged due to altered pharmacokinetic (PK)
      properties in this vulnerable group. The aim of this study was to determine the
      PK profile of AL in pregnant and nonpregnant women and assess their therapeutic
      outcome. Thirty-three pregnant women and 22 nonpregnant women with malaria were
      treated with AL (80/480 mg) twice daily for 3 days. All patients provided five
      venous plasma samples for drug quantification at random times over 7 days. Inter-
      and intraindividual variability was assessed, and the effects of covariates were
      quantified using a nonlinear mixed-effects modeling approach (NONMEM). A one
      compartment model with first-order absorption and elimination with linear
      metabolism from drug to metabolite fitted the data best for both arthemether (AM)
      and lumefantrine (LF) and their metabolites. Pregnancy status and diarrhea showed
      a significant influence on LF PK. The relative bioavailability of lumefantrine
      and its metabolism rate into desmethyl-lumefantrine were, respectively, 34% lower
      and 78% higher in pregnant women than in nonpregnant patients. The overall PCR
      uncorrected treatment failure rates were 18% in pregnant women and 5% in
      nonpregnant women (odds ratio [OR] = 4.04; P value of 0.22). A high median day 7
      lumefantrine concentration was significantly associated with adequate clinical
      and parasitological response (P = 0.03). The observed reduction in the relative
      bioavailability of lumefantrine in pregnant women may explain the higher
      treatment failure in this group, mostly due to lower posttreatment prophylaxis.
      Hence, a modified treatment regimen of malaria in pregnancy should be considered.

PMID- 24867987
TI  - In vivo and in vitro acquisition of resistance to voriconazole by Candida krusei.
AB  - Candida krusei is an important agent of opportunistic infections that often
      displays resistance to several antifungals. We describe here the in vivo
      acquisition of resistance to voriconazole (VRC) by C. krusei isolates recovered
      from a leukemia patient during a long period of VRC therapy. In order to mimic
      the in vivo development of VRC resistance, a susceptible C. krusei isolate was
      exposed daily to 1 MUg/ml of VRC in vitro. Interestingly, after 5 days of
      exposure to VRC, a MIC of 4 MUg/ml was achieved; this value remained constant
      after 25 additional days of treatment with VRC and also after 30 consecutive days
      of incubation in VRC-free medium. Our objective was to determine the associated
      molecular resistance mechanisms, such as expression of efflux pump genes and
      ERG11 gene mutations, among the resistant strains. Synergistic effects between
      the efflux blocker tacrolimus (FK506) and VRC were found in all of the resistant
      strains. Moreover, ABC1 gene expression increased over time in both the in vivo-
      and in vitro-induced resistant strains, in contrast to the ABC2 and ERG11 genes,
      whose expression was invariably lower and constant. ERG11 gene sequencing showed
      two different types of mutations, i.e., heterozygosity at T1389T/C, corresponding
      to synonymous mutations, in C. krusei strains and a missense mutation at position
      T418C, resulting in a change from Tyr to His, among resistant C. krusei clinical
      isolates. This study highlights the relevance of ATP-dependent efflux pump
      (namely, Abc1p) activity in VRC resistance and describes new mutations in the
      ERG11 gene among resistant C. krusei clinical isolates. 

PMID- 24867988
TI  - Carbapenem-resistant Klebsiella pneumoniae strains exhibit diversity in
      aminoglycoside-modifying enzymes, which exert differing effects on plazomicin and
      other agents.
AB  - We measured in vitro activity of plazomicin, a next-generation aminoglycoside,
      and other aminoglycosides against 50 carbapenem-resistant Klebsiella pneumoniae
      strains from two centers and correlated the results with the presence of various
      aminoglycoside-modifying enzymes (AMEs). Ninety-four percent of strains were
      sequence type 258 (ST258) clones, which exhibited 5 ompK36 genotypes; 80% and 10%
      of strains produced Klebsiella pneumoniae carbapenemase 2 (KPC-2) and KPC-3,
      respectively. Ninety-eight percent of strains possessed AMEs, including AAC(6')
      Ib (98%), APH(3')-Ia (56%), AAC(3)-IV (38%), and ANT(2")-Ia (2%). Gentamicin,
      tobramycin, and amikacin nonsusceptibility rates were 40, 98, and 16%,
      respectively. Plazomicin MICs ranged from 0.25 to 1 MUg/ml. Tobramycin and
      plazomicin MICs correlated with gentamicin MICs (r = 0.75 and 0.57,
      respectively). Plazomicin exerted bactericidal activity against 17% (1* MIC) and
      94% (4* MIC) of strains. All strains with AAC(6')-Ib were tobramycin-resistant;
      16% were nonsusceptible to amikacin. AAC(6')-Ib combined with another AME was
      associated with higher gentamicin, tobramycin, and plazomicin MICs than AAC(6')
      Ib alone (P = 0.01, 0.0008, and 0.046, respectively). The presence of AAC(3)-IV
      in a strain was also associated with higher gentamicin, tobramycin, and
      plazomicin MICs (P = 0.0006, P < 0.0001, and P = 0.01, respectively). The
      combination of AAC(6')-Ib and another AME, the presence of AAC(3)-IV, and the
      presence of APH(3')-Ia were each associated with gentamicin resistance (P =
      0.0002, 0.003, and 0.01, respectively). In conclusion, carbapenem-resistant K.
      pneumoniae strains (including ST258 clones) exhibit highly diverse antimicrobial
      resistance genotypes and phenotypes. Plazomicin may offer a treatment option
      against strains resistant to other aminoglycosides. The development of molecular
      assays that predict antimicrobial responses among carbapenem-resistant K.
      pneumoniae strains should be a research priority.

PMID- 24867989
TI  - Alternative strategies for proof-of-principle studies of antibacterial agents.
AB  - The proof that a new antibacterial agent is not only active in vitro but also
      effective in vivo under clinically relevant conditions is currently provided (i)
      by using appropriate nonclinical models of infection and pharmacokinetic
      pharmacodynamic (PK-PD) analysis providing evidence of the likelihood of clinical
      efficacy and (ii) by examining the study drug in exploratory clinical trials, as
      well as dose and schedule finding during phase II of clinical development. This
      approach is both time-consuming and costly. Furthermore, PK-PD targets for any
      novel antibacterial agent cannot be derived from studies with experimental
      animals. Therefore, alternative strategies have to be identified to prove the
      principle that a novel antibacterial agent is active under clinically relevant
      conditions. This review summarizes evidence that the quantitative analysis of
      shifts in the viable counts of pathogens in infected patients or the evaluation
      of the PD effect of an investigational agent on indicator organisms of the human
      resident microflora or colonizers of healthy volunteers, if paralleled with PK
      monitoring of serum and the target site, provides an alternative to a classical
      proof-of-principle study in the course of a phase II study program. 

PMID- 24867990
TI  - beta-Lactam resistance in methicillin-resistant Staphylococcus aureus USA300 is
      increased by inactivation of the ClpXP protease.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) has acquired the mecA gene
      encoding a peptidoglycan transpeptidase, penicillin binding protein 2a (PBP2a),
      which has decreased affinity for beta-lactams. Quickly spreading and highly
      virulent community-acquired (CA) MRSA strains recently emerged as a frequent
      cause of infection in individuals without exposure to the health care system. In
      this study, we found that the inactivation of the components of the ClpXP
      protease substantially increased the beta-lactam resistance level of a CA-MRSA
      USA300 strain, suggesting that the proteolytic activity of ClpXP controls one or
      more pathways modulating beta-lactam resistance. These pathways do not involve
      the control of mecA expression, as the cellular levels of PBP2a were unaltered in
      the clp mutants. An analysis of the cell envelope properties of the clpX and clpP
      mutants revealed a number of distinct phenotypes that may contribute to the
      enhanced beta-lactam tolerance. Both mutants displayed significantly thicker cell
      walls, increased peptidoglycan cross-linking, and altered composition of
      monomeric muropeptide species compared to those of the wild types. Moreover,
      changes in Sle1-mediated peptidoglycan hydrolysis and altered processing of the
      major autolysin Atl were observed in the clp mutants. In conclusion, the results
      presented here point to an important role for the ClpXP protease in controlling
      cell wall metabolism and add novel insights into the molecular factors that
      determine strain-dependent beta-lactam resistance. 

PMID- 24867992
TI  - Eight more ways to deal with antibiotic resistance.
AB  - The fight against antibiotic resistance must be strengthened. We propose actions
      that U.S. government agencies and private sector entities can take to build a
      more comprehensive effort. These actions can increase the viability of investing
      in new antibiotics, ensure the quality and stewardship of all antibiotics, and
      make responses to emerging resistance more informed. Success requires the
      thoughtful exercise of federal authority and a firm commitment to share data and
      reward developers for the value generated with new, life-saving antibiotics. 

PMID- 24867991
TI  - Antagonism between bacteriostatic and bactericidal antibiotics is prevalent.
AB  - Combination therapy is rarely used to counter the evolution of resistance in
      bacterial infections. Expansion of the use of combination therapy requires
      knowledge of how drugs interact at inhibitory concentrations. More than 50 years
      ago, it was noted that, if bactericidal drugs are most potent with actively
      dividing cells, then the inhibition of growth induced by a bacteriostatic drug
      should result in an overall reduction of efficacy when the drug is used in
      combination with a bactericidal drug. Our goal here was to investigate this
      hypothesis systematically. We first constructed time-kill curves using five
      different antibiotics at clinically relevant concentrations, and we observed
      antagonism between bactericidal and bacteriostatic drugs. We extended our
      investigation by performing a screen of pairwise combinations of 21 different
      antibiotics at subinhibitory concentrations, and we found that strong
      antagonistic interactions were enriched significantly among combinations of
      bacteriostatic and bactericidal drugs. Finally, since our hypothesis relies on
      phenotypic effects produced by different drug classes, we recreated these
      experiments in a microfluidic device and performed time-lapse microscopy to
      directly observe and quantify the growth and division of individual cells with
      controlled antibiotic concentrations. While our single-cell observations
      supported the antagonism between bacteriostatic and bactericidal drugs, they
      revealed an unexpected variety of cellular responses to antagonistic drug
      combinations, suggesting that multiple mechanisms underlie the interactions. 

PMID- 24867994
TI  - Alternative screening approaches for discovery of Middle East respiratory
      syndrome coronavirus inhibitors.
AB  - Two coronaviruses causing severe respiratory disease and high mortality rates
      emerging within the past dozen years reinforces the need for clinically
      efficacious antivirals targeting coronaviruses. Alternative screening approaches
      for antivirals against the recently emergent Middle East respiratory syndrome
      coronavirus (MERS-CoV) may provide lead compounds to address this need. Two
      Antimicrobial Agents and Chemotherapy (AAC) papers screened libraries of approved
      compounds that may potentially be repurposed as MERS-CoV antivirals. A third AAC
      paper showed that a previously described severe acute respiratory syndrome
      coronavirus (SARS-CoV) helicase inhibitor also has activity against MERS-CoV. 

PMID- 24867993
TI  - Activity of daptomycin or linezolid in combination with rifampin or gentamicin
      against biofilm-forming Enterococcus faecalis or E. faecium in an in vitro
      pharmacodynamic model using simulated endocardial vegetations and an in vivo
      survival assay using Galleria mellonella larvae.
AB  - Enterococci are the third most frequent cause of infective endocarditis. A high
      inoculum stationary-phase in vitro pharmacodynamic model with simulated
      endocardial vegetations was used to simulate the human pharmacokinetics of
      daptomycin at 6 or 10 mg/kg of body weight/day or linezolid at 600 mg every 12 h
      (q12h), alone or in combination with gentamicin at 1.3 mg/kg q12h or rifampin at
      300 mg q8h or 900 mg q24h. Biofilm-forming, vancomycin-susceptible Enterococcus
      faecalis and vancomycin-resistant Enterococcus faecium (vancomycin-resistant
      enterococcus [VRE]) strains were tested. At 24, 48, and 72 h, all daptomycin
      containing regimens demonstrated significantly more activity (decline in CFU/g)
      than any linezolid-containing regimen against biofilm-forming E. faecalis. The
      addition of gentamicin to daptomycin (at 6 or 10 mg/kg) in the first 24 h
      significantly improved bactericidal activity. In contrast, the addition of
      rifampin delayed the bactericidal activity of daptomycin against E. faecalis, and
      the addition of rifampin antagonized the activities of all regimens against VRE
      at 24 h. Also, against VRE, the addition of gentamicin to linezolid at 72 h
      improved activity and was bactericidal. Rifampin significantly antagonized the
      activity of linezolid against VRE at 72 h. In in vivo Galleria mellonella
      survival assays, linezolid and daptomycin improved survival. Daptomycin at 10
      mg/kg improved survival significantly over that with linezolid against E.
      faecalis. The addition of gentamicin improved the efficacy of daptomycin against
      E. faecalis and those of linezolid and daptomycin against VRE. We conclude that
      in enterococcal infection models, daptomycin has more activity than linezolid
      alone. Against biofilm-forming E. faecalis, the addition of gentamicin in the
      first 24 h causes the most rapid decline in CFU/g. Of interest, the addition of
      rifampin decreased the activity of daptomycin against both E. faecalis and VRE. 

PMID- 24867996
TI  - A noncompaction reaction.

PMID- 24867998
TI  - Type A aortic dissection mimicking a saddle pulmonary embolus on computed
      tomographic angiography.

PMID- 24867999
TI  - Left atrial rhabdomyosarcoma.

PMID- 24867995
TI  - Epidemiology and pathophysiology of mitral valve prolapse: new insights into
      disease progression, genetics, and molecular basis.

PMID- 24868000
TI  - Dual antiplatelet therapy for heart disease.

PMID- 24868001
TI  - Letter by Heidrich et al regarding article, "Inositol 1,4,5-trisphosphate
      receptors and human left ventricular myocytes".

PMID- 24868004
TI  - An additional case of breast tumor resembling the tall cell variant of papillary
      thyroid carcinoma.
AB  - A type of breast tumor histopathologically similar to the papillary thyroid
      carcinoma has been described and named "Breast tumor resembling the tall cell
      variant of papillary thyroid carcinoma." Because breast is not an uncommon site
      for metastasis and about 5% of all such cases are of the thyroid origin, it is
      important to be aware of the existence of mammary tumors that can closely mimic a
      thyroid tumor representing a dangerous diagnostic pitfall that can also lead to
      unnecessary clinical investigations. Here, we describe a singular case of "Breast
      tumor resembling the tall cell variant of papillary thyroid carcinoma" showing an
      amazing macroscopic and microscopic resemblance with thyroid tissue harboring a
      papillary carcinoma. 

PMID- 24868002
TI  - Response to letter regarding article "Inositol 1,4,5-trisphosphate receptors and
      human left ventricular myocytes".

PMID- 24868005
TI  - Anaplastic lymphoma kinase-positive large B-cell lymphoma: description of a case
      with an unexpected clinical outcome.
AB  - Anaplastic lymphoma kinase-positive (ALK-positive) large B-cell lymphoma is a
      rare and aggressive variant of large B-cell lymphoma (LBCL), first reported by
      Delsol et al in 1997, showing distinctive morphologic, immunophenotypic and
      cytogenetic features. The latest 2008 World Health Organization Classification of
      Tumours of Haematopoietic and Lymphoid tissues recognizes ALK-positive LBCL as a
      separate entity. Here, we report a case of ALK-positive large B-cell lymphoma in
      a 53-year-old man with diffuse abdominal and mediastinal lymph-nodes involvement.
      According to the Ann Arbor staging system, the patient had a stage IIIB lymphoma.
      The age-adjusted International Prognostic Index was 2 (stage III and elevated
      lactate dehydrogenase), so the disease was considered high risk. The patient
      underwent chemotherapy, radiotherapy, and an autologous stem cell
      transplantation. The patient is alive and free of disease 35 months after
      diagnosis. 

PMID- 24868008
TI  - Spectrum of neurodevelopmental disabilities: a cohort study in hungary.
AB  - The spectrum of neurodevelopmental disabilities was studied in a cohort of
      patients in Hungary. A search for etiologies and assessment of the degree of
      intellectual disability were carried out. The study included 241 (131 boys)
      patients. Disability occurred without any prenatal, perinatal, and/or neonatal
      adverse events in 167 patients. They were classified into the following
      subgroups: genetic syndromes with recognized etiology, global developmental
      delay/intellectual disability in association with dysmorphic features but unknown
      etiology, global developmental delay/intellectual disability without dysmorphic
      features and recognized etiology, brain malformations, inborn errors of
      metabolism, leukoencephalopathies, epileptic syndromes, developmental language
      impairment, and neuromuscular disorders. Adverse events occurred in 74 children
      classified into subgroups such as cerebral palsy after delivery preterm or at
      term, and disabilities without cerebral palsy. The etiology was identified in
      66.4%, and genetic diagnosis was found in 19.5%. Classification of
      neurodevelopmental disorders contribute to etiological diagnosis, proper
      rehabilitation, and genetic counseling. 

PMID- 24868009
TI  - A potential wound-healing-promoting peptide from salamander skin.
AB  - Although it is well known that wound healing proceeds incredibly quickly in
      urodele amphibians, such as newts and salamanders, little is known about skin
      wound healing, and no bioactive/effector substance that contributes to wound
      healing has been identified from these animals. As a step toward understanding
      salamander wound healing and skin regeneration, a potential wound-healing
      promoting peptide (tylotoin; KCVRQNNKRVCK) was identified from salamander skin of
      Tylototriton verrucosus. It shows comparable wound-healing-promoting ability
      (EC50=11.14 MUg/ml) with epidermal growth factor (EGF;
      NSDSECPLSHDGYCLHDGVCMYIEALDKYACNCVVGYIGERCQYRDLKWWELR) in a murine model of full
      thickness dermal wound. Tylotoin directly enhances the motility and proliferation
      of keratinocytes, vascular endothelial cells, and fibroblasts, resulting in
      accelerated reepithelialization and granulation tissue formation in the wound
      site. Tylotoin also promotes the release of transforming growth factor beta1 (TGF
      beta1) and interleukin 6 (IL-6), which are essential in the wound healing
      response. Gene-encoded tylotoin secreted in salamander skin is possibly an
      effector molecule for skin wound healing. This study may facilitate understanding
      of the cellular and molecular events that underlie quick wound healing in
      salamanders.

PMID- 24868010
TI  - Feedforward activation of endothelial ENaC by high sodium.
AB  - Kidney epithelial sodium channels (ENaCs) are known to be inactivated by high
      sodium concentrations (feedback inhibition). Recently, the endothelial sodium
      channel (EnNaC) was identified to control the nanomechanical properties of the
      endothelium. EnNaC-dependent endothelial stiffening reduces the release of nitric
      oxide, the hallmark of endothelial dysfunction. To study the regulatory impact of
      sodium on EnNaC, endothelial cells (EA.hy926 and ex vivo mouse endothelium) were
      incubated in aldosterone-free solutions containing either low (130 mM) or high
      (150 mM) sodium concentrations. By applying atomic force microscopy-based
      nanoindentation, an unexpected positive correlation between increasing sodium
      concentrations and cortical endothelial stiffness was observed, which can be
      attributed to functional EnNaC. In particular, an acute rise in sodium
      concentration (+20 mM) was sufficient to increase EnNaC membrane abundance by 90%
      and stiffening of the endothelial cortex by 18%. Despite the absence of exogenous
      aldosterone, these effects were prevented by the aldosterone synthase inhibitor
      FAD286 (100 nM) or the mineralocorticoid receptor (MR)-antagonist spironolactone
      (100 nM), indicating endogenous aldosterone synthesis and MR-dependent signaling.
      Interestingly, in the presence of high-sodium concentrations, FAD286 increased
      the transcription of the MR by 69%. Taken together, a novel feedforward
      activation of EnNaC by sodium is proposed that contrasts ENaC feedback inhibition
      in kidney.

PMID- 24868011
TI  - Mannan-binding lectin-associated serine protease 2 is critical for the
      development of renal ischemia reperfusion injury and mediates tissue injury in
      the absence of complement C4.
AB  - Mannan-binding lectin-associated serine protease 2 (MASP-2) has been described as
      the essential enzyme for the lectin pathway (LP) of complement activation. Since
      there is strong published evidence indicating that complement activation via the
      LP critically contributes to ischemia reperfusion (IR) injury, we assessed the
      effect of MASP-2 deficiency in an isogenic mouse model of renal transplantation.
      The experimental transplantation model used included nephrectomy of the remaining
      native kidney at d 5 post-transplantation. While wild-type (WT) kidneys grafted
      into WT recipients (n=7) developed acute renal failure (control group), WT grafts
      transplanted into MASP-2-deficient recipients (n=7) showed significantly better
      kidney function, less C3 deposition, and less IR injury. In the absence of donor
      or recipient complement C4 (n=7), the WT to WT phenotype was preserved,
      indicating that the MASP-2-mediated damage was independent of C4 activation. This
      C4-bypass MASP-2 activity was confirmed in mice deficient for both MASP-2 and C4
      (n=7), where the protection from postoperative acute renal failure was no greater
      than in mice with MASP-2 deficiency alone. Our study highlights the role of LP
      activation in renal IR injury and indicates that injury occurs through MASP-2
      dependent activation events independent of C4.

PMID- 24868012
TI  - Hydrocarbon Deposition Attenuates Osteoblast Activity on Titanium.
AB  - Although the reported percentage of bone-implant contact is far lower than 100%,
      the cause of such low levels of bone formation has rarely been investigated. This
      study tested the negative biological effect of hydrocarbon deposition onto
      titanium surfaces, which has been reported to be inevitable. Osteogenic MC3T3-E1
      cells were cultured on titanium disks on which the carbon concentration was
      experimentally regulated to achieve carbon/titanium (C/Ti) ratios of 0.3, 0.7,
      and 1.0. Initial cellular activities such as cell attachment and cell spreading
      were concentration-dependently suppressed by the amount of carbon on the titanium
      surface. The osteoblastic functions of alkaline phosphatase activity and calcium
      mineralization were also reduced by more than 40% on the C/Ti (1.0) surface.
      These results indicate that osteoblast activity is influenced by the degree of
      hydrocarbon contamination on titanium implants and suggest that hydrocarbon
      decomposition before implant placement may increase the biocompatibility of
      titanium. 

PMID- 24868013
TI  - Selective beta2-adrenergic Antagonist Butoxamine Reduces Orthodontic Tooth
      Movement.
AB  - Recently, involvement of the sympathetic nervous system in bone metabolism has
      attracted attention. beta2-Adrenergic receptor (beta2-AR) is presented on
      osteoblastic and osteoclastic cells. We previously demonstrated that beta-AR
      blockers at low dose improve osteoporosis with hyperactivity of the sympathetic
      nervous system via beta2-AR blocking, while they may have a somewhat inhibitory
      effect on osteoblastic activity at high doses. In this study, the effects of
      butoxamine (BUT), a specific beta2-AR antagonist, on tooth movement were examined
      in spontaneously hypertensive rats (SHR) showing osteoporosis with hyperactivity
      of the sympathetic nervous system. We administered BUT (1 mg/kg) orally, and
      closed-coil springs were inserted into the upper-left first molar. After
      sacrifice, we calculated the amount of tooth movement and analyzed the trabecular
      microarchitecture and histomorphometry. The distance in the SHR control was
      greater than that in the Wistar-Kyoto rat group, but no significant difference
      was found in the SHR treated with BUT compared with the Wistar-Kyoto rat control.
      Analysis of bone volume per tissue volume, trabecular number, and osteoclast
      surface per bone surface in the alveolar bone showed clear bone loss by an
      increase of bone resorption in SHR. In addition, BUT treatment resulted in a
      recovery of alveolar bone loss. Furthermore, TH-immunoreactive nerves in the
      periodontal ligament were increased by tooth movement, and BUT administration
      decreased TH-immunoreactive nerves. These results suggest that BUT prevents
      alveolar bone loss and orthodontic tooth movement via beta2-AR blocking. 

PMID- 24868015
TI  - Transcription of nuclear organellar DNA in a model plant system.
AB  - Endosymbiotic gene transfer from cytoplasmic organelles (chloroplasts and
      mitochondria) to the nucleus is an ongoing process in land plants. Although the
      frequency of organelle DNA migration is high, functional gene transfer is rare
      because a nuclear promoter is thought necessary for activity in the nucleus. Here
      we show that a chloroplast promoter, 16S rrn, drives nuclear transcription,
      suggesting that a transferred organellar gene may become active without obtaining
      a nuclear promoter. Examining the chromatin status of a known de novo chloroplast
      integrant indicates that plastid DNA inserts into open chromatin and that this
      relaxed condition is maintained after integration. Transcription of nuclear
      organelle DNA integrants was explored at the whole genome level by analyzing RNA
      seq data of Oryza sativa subsp. japonica, and utilizing sequence polymorphisms to
      unequivocally discriminate nuclear organelle DNA transcripts from those of bona
      fide cytoplasmic organelle DNA. Nuclear copies of organelle DNA that are
      transcribed show a spectrum of transcriptional activity but at comparatively low
      levels compared with the majority of other nuclear genes. 

PMID- 24868014
TI  - Low Concentration H(2)O(2)/TiO_N in Office Bleaching: A Randomized Clinical
      Trial.
AB  - OBJECTIVES: The purpose of this randomized double-blinded clinical trial was to
      test the efficacy and tooth sensitivity promoted by the use of an in-office 15%
      H(2)O(2) bleaching agent containing nanoparticles of TiO_N photocatalyzed with
      LED/laser light (HP15) and a control of 35% H2O2 (HP35). METHODS: Forty healthy
      volunteers, both sexes, aged 18 to 25 yr, were randomly distributed in 2 groups:
      HP15 (n = 20) was treated in 3 sessions of 48 min each, and HP35 (n = 20) was
      treated in 3 sessions of 45 min each. The efficacy (E) was evaluated by DeltaE
      values measured via reflectance spectroscopy. The tooth sensitivity (S) was
      analyzed by visual analog scale (low, average, high, very high). The absolute
      risk reduction and the number needed to treat index were calculated. The data
      were analyzed by mixed repeated measures analysis of variance with Bonferroni
      correction t test (alpha = 0.05). RESULTS: For the efficacy, significant
      differences were found for number of bleaching sessions (p = .0001; [Formula: see
      text] = 0.73 and pi = 1.000) and for the interaction of number of sessions and
      bleaching protocols (p = .0001; [Formula: see text] = 0.319 and pi = 1.000. The
      tooth sensitivity level showed significant differences only between the bleaching
      protocols. Absolute risk reduction calculated was 52% and number needed to treat,
      1.92. CONCLUSIONS: The bleaching agent with the lower concentration (HP15)
      promoted lower levels of tooth sensitivity and presented greater efficacy
      compared to the control (HP35) in patients between 18 and 25 yr old. The
      limitation of short-term evaluation did not provide information about the
      longevity of the tooth bleaching (Brazilian Clinical Trials Registry Re Bec no.
      U1111-1150-4466).

PMID- 24868017
TI  - In the United States, a Mother's Plans for Infant Feeding Are Associated with Her
      Plans for Employment.
AB  - BACKGROUND: The American Academy of Pediatrics recommends 6 months of exclusive
      breastfeeding, however, only 16% of US infants meet this recommendation. Shorter
      exclusive/predominant breastfeeding durations have been observed from women who
      return to work early and/or full-time. OBJECTIVE: We assessed the relationship
      between prenatal plans for maternity leave duration and return to full-time/part
      time status and plans for exclusive breastfeeding. METHODS: This study included
      2348 prenatally employed women from the Infant Feeding Practices Study II (2005
      2007) who planned to return to work in the first year postpartum. Bivariate
      analysis and logistic regression were used to describe the association of
      maternity leave duration and return status with plans for infant feeding.
      RESULTS: Overall, 59.5% of mothers planned to exclusively breastfeed in the first
      few weeks. Mothers planning to return to work within 6 weeks had 0.60 times the
      odds (95% confidence interval [CI], 0.46-0.77) and mothers planning to return
      between 7 and 12 weeks had 0.72 times the odds (95% CI, 0.56-0.92) of planning to
      exclusively breastfeed compared with mothers who were planning to return after 12
      weeks. Prenatal plans to return full-time (>= 30 hours/week vs part-time) were
      also associated with lower odds of planning to exclusively breastfeed (adjusted
      odds ratio = 0.61; 95% CI, 0.51-0.77). CONCLUSION: Mothers planning to return to
      work before 12 weeks and/or full-time were less likely to plan to exclusively
      breastfeed. Longer maternity leave and/or part-time return schedules may increase
      the proportion of mothers who plan to exclusively breastfeed.

PMID- 24868018
TI  - Critical appraisal of locoregional failure and systemic disease progression after
      preoperative chemoradiation of esophageal adenocarcinoma. Reply to R. Gertler et
      al.

PMID- 24868016
TI  - Recurrent horizontal transfers of Chapaev transposons in diverse invertebrate and
      vertebrate animals.
AB  - Horizontal transfer (HT) of a transposable element (TE) into a new genome is
      regarded as an important force to drive genome variation and biological
      innovation. In addition, HT also plays an important role in the persistence of
      TEs in eukaryotic genomes. Here, we provide the first documented example for the
      repeated HT of three families of Chapaev transposons in a wide range of animal
      species, including mammals, reptiles, jawed fishes, lampreys, insects, and in an
      insect bracovirus. Multiple alignments of the Chapaev transposons identified in
      these species revealed extremely high levels of nucleotide sequence identity (79
      99%), which are inconsistent with vertical evolution given the deep divergence
      time separating these host species. Rather, the discontinuous distribution
      amongst species and lack of purifying selection acting on these transposons
      strongly suggest that they were independently and horizontally transferred into
      these species lineages. The detection of Chapaev transposons in an insect
      bracovirus indicated that these viruses might act as a possible vector for the
      horizontal spread of Chapaev transposons. One of the Chapaev families was also
      shared by lampreys and some of their common hosts (such as sturgeon and
      paddlefish), which suggested that parasite-host interaction might facilitate HTs.

PMID- 24868019
TI  - Critical appraisal of locoregional failure and systemic disease progression after
      preoperative chemoradiation of esophageal adenocarcinoma.

PMID- 24868020
TI  - Multigene panel testing: planning the next generation of research studies in
      clinical cancer genetics.

PMID- 24868021
TI  - Acute Radiation Skin Toxicity Associated With BRAF Inhibitors.

PMID- 24868022
TI  - Risk of hospitalization according to chemotherapy regimen in early-stage breast
      cancer.
AB  - PURPOSE: To compare the risk of hospitalization between patients with early-stage
      breast cancer who received different chemotherapy regimens. PATIENT AND METHODS:
      We identified 3,567 patients older than age 65 years from the SEER/Texas Cancer
      Registry-Medicare database and 9,327 patients younger than age 65 years from the
      MarketScan database who were diagnosed with early-stage breast cancer between
      2003 and 2007. The selection was nonrandomized and nonprospectively collected. We
      categorized patients according to the regimens they received: docetaxel (T) and
      cyclophosphamide (C), doxorubicin (A) and C, TAC, AC + T, dose-dense AC +
      paclitaxel (P) or AC + weekly P. We compared the rates of chemotherapy-related
      hospitalizations that occurred within 6 months of chemotherapy initiation and
      used multivariable logistic regression analysis to identify the factors
      associated with these hospitalizations. RESULTS: Among patients younger than age
      65 years, the hospitalization rates ranged from 6.2% (dose-dense AC + P) to 10.0%
      (TAC), and those who received TAC and AC + T had significantly higher rates of
      hospitalization than did patients who received TC. Among patients older than age
      65 years, these rates ranged from 12.7% (TC) to 24.2% (TAC) and the rates of
      hospitalization of patients who received TAC, AC + T, AC, or AC + weekly P were
      higher than those of patients who received TC. CONCLUSION: TAC and AC + T were
      associated with the highest risk of hospitalization in patients younger than age
      65 years. Among patients older than age 65 years, all regimens (aside from dose
      dense AC + P) were associated with a higher risk of hospitalization than TC.
      Results may be affected by selection biases where less aggressive regimens are
      offered to frailer patients.

PMID- 24868023
TI  - Adjuvant endocrine therapy for women with hormone receptor-positive breast
      cancer: american society of clinical oncology clinical practice guideline focused
      update.
AB  - PURPOSE: To update the ASCO clinical practice guideline on adjuvant endocrine
      therapy on the basis of emerging data on the optimal duration of treatment,
      particularly adjuvant tamoxifen. METHODS: ASCO convened the Update Committee and
      conducted a systematic review of randomized clinical trials from January 2009 to
      June 2013 and analyzed three historical trials. Guideline recommendations were
      based on the Update Committee's review of the evidence. Outcomes of interest
      included survival, disease recurrence, and adverse events. RESULTS: This
      guideline update reflects emerging data on duration of tamoxifen treatment. There
      have been five studies of tamoxifen treatment beyond 5 years of therapy. The two
      largest studies with longest reported follow-up show a breast cancer survival
      advantage with 10-year durations of tamoxifen use. In addition to modest gains in
      survival, extended therapy with tamoxifen for 10 years compared with 5 years was
      associated with lower risks of breast cancer recurrence and contralateral breast
      cancer. RECOMMENDATIONS: Previous ASCO guidelines recommended treatment of women
      who have hormone receptor-positive breast cancer and are premenopausal with 5
      years of tamoxifen, and those who are postmenopausal a minimum of 5 years of
      adjuvant therapy with an aromatase inhibitor or tamoxifen followed by an
      aromatase inhibitor (in sequence). If women are pre- or perimenopausal and have
      received 5 years of adjuvant tamoxifen, they should be offered 10 years total
      duration of tamoxifen. If women are postmenopausal and have received 5 years of
      adjuvant tamoxifen, they should be offered the choice of continuing tamoxifen or
      switching to an aromatase inhibitor for 10 years total adjuvant endocrine
      therapy.

PMID- 24868024
TI  - Lapatinib plus paclitaxel versus paclitaxel alone in the second-line treatment of
      HER2-amplified advanced gastric cancer in Asian populations: TyTAN--a randomized,
      phase III study.
AB  - PURPOSE: In Asian countries, paclitaxel once per week is used as second-line
      treatment in advanced gastric cancer, including human epidermal growth factor
      receptor 2 (HER2) -positive tumors. The role of anti-HER2 agents, including
      lapatinib, in this setting and population is unclear. PATIENTS AND METHODS: TyTAN
      was a two-part, parallel-group, phase III study in Asian patients. An open-label,
      dose-optimization phase (n = 12) was followed by a randomized phase (n = 261), in
      which patients who were HER2 positive by fluorescence in situ hybridization
      (FISH) received lapatinib 1,500 mg once per day plus once-per-week paclitaxel 80
      mg/m(2) or paclitaxel alone. The primary end point was overall survival (OS).
      Secondary end points included progression-free survival (PFS), time to
      progression (TTP), overall response rate (ORR), time to response, response
      duration, and safety. Analyses were based on immunohistochemistry (IHC) and
      gastrectomy status, prior trastuzumab therapy, and regional subpopulations.
      RESULTS: Median OS was 11.0 months with lapatinib plus paclitaxel versus 8.9
      months with paclitaxel alone (P = .1044), with no significant difference in
      median PFS (5.4 v 4.4 months) or TTP (5.5 v 4.4 months). ORR was higher with
      lapatinib plus paclitaxel versus paclitaxel alone (odds ratio, 3.85; P < .001).
      Better efficacy with lapatinib plus paclitaxel was demonstrated in IHC3+ compared
      with IHC0/1+ and 2+ patients and in Chinese compared with Japanese patients. A
      similar proportion of patients experienced adverse events with each treatment
      (lapatinib plus paclitaxel, 100% v paclitaxel alone, 98%). CONCLUSION: Lapatinib
      plus paclitaxel demonstrated activity in the second-line treatment of patients
      with HER2 FISH-positive IHC3+ advanced gastric cancer but did not significantly
      improve OS in the intent-to-treat population.

PMID- 24868025
TI  - Letter to cancer center directors: Progress in quantitative imaging as a means to
      predict and/or measure tumor response in cancer therapy trials.

PMID- 24868027
TI  - Enhancing therapeutic decision making when options abound: toxicities matter.

PMID- 24868028
TI  - Familial GI Stromal Tumor With Loss of Heterozygosity and Amplification of Mutant
      KIT.

PMID- 24868026
TI  - Two dimensions in targeting HER2.

PMID- 24868029
TI  - Longitudinal assessment of chemotherapy-induced alterations in brain activation
      during multitasking and its relation with cognitive complaints.
AB  - PURPOSE: To examine whether cognitive complaints after treatment for breast
      cancer are associated with detectable changes in brain activity during
      multitasking. PATIENTS AND METHODS: Eighteen patients who were scheduled to
      receive chemotherapy performed a functional magnetic resonance imaging
      multitasking task in the scanner before the start of treatment (t1) and 4 to 6
      months after finishing treatment (t2). Sixteen patients who were not scheduled to
      receive chemotherapy and 17 matched healthy controls performed the same task at
      matched intervals. Task difficulty level was adjusted individually to match
      performance across participants. Statistical Parametric Mapping 8 (SPM8) software
      was used for within-group, between-group, and group-by-time interaction image
      analyses. RESULTS: Voxel-based paired t tests revealed significantly decreased
      activation (P < .05) from t1 to t2 at matched performance in the multitasking
      network of chemotherapy-treated patients, whereas no changes were noted in either
      of the control groups. At baseline, there were no differences between the groups.
      Furthermore, in contrast to controls, the chemotherapy-treated patients reported
      a significant increase in cognitive complaints (P < .05) at t2. Significant (P <
      .05) correlations were found between these increases and decreases in
      multitasking-related brain activation. Moreover, a significant group-by-time
      interaction (P < .05) was found whereby chemotherapy-treated patients showed
      decreased activation and healthy controls did not. CONCLUSION: These results
      suggest that changes in brain activity may underlie chemotherapy-induced
      cognitive complaints. The observed changes might be related to chemotherapy
      induced damage to the brain or reduced connectivity between brain regions rather
      than to changes in effort or changes in functional strategy. To the best of our
      knowledge, this is the first longitudinal study providing evidence for a
      relationship between longitudinal changes in cognitive complaints and changes in
      brain activation after chemotherapy.

PMID- 24868030
TI  - Adjuvant chemotherapy in older women with breast cancer: who and what?
AB  - A 73-year-old woman has been diagnosed with a mammographically detected grade 3,
      2.2-cm invasive ductal carcinoma that is sentinel lymph node negative, estrogen
      receptor positive (80%), progesterone receptor negative, and human epidermal
      growth factor receptor 2 negative (0 by immunohistochemistry). A gene expression
      assay (Oncotype DX, Genomic Health, Redwood City, CA) showed a recurrence score
      of 28. Except for well-controlled hypertension and some aches and pains in her
      hands and knees, she has no other major illnesses. Her medications include an
      antihypertensive, vitamin D, and calcium. She discontinued cigarette smoking 20
      years ago and has an occasional glass of wine. She describes her health as good,
      is fully functional, drives, has had no falls, and provides the majority of care
      for her sick husband. Her blood pressure is 146/88, her body mass index is 29.7,
      and her physical examination is normal. She is aware of the benefits and risks of
      adjuvant endocrine therapy and has been referred to discuss the role of
      chemotherapy.

PMID- 24868031
TI  - Lenalidomide and rituximab for the initial treatment of patients with chronic
      lymphocytic leukemia: a multicenter clinical-translational study from the chronic
      lymphocytic leukemia research consortium.
AB  - PURPOSE: Lenalidomide is an immunomodulatory agent with therapeutic activity in
      chronic lymphocytic leukemia (CLL). In preclinical models, lenalidomide acted
      synergistically with rituximab. The CLL Research Consortium initiated a phase II
      study to evaluate this combination in treatment-naive patients. PATIENTS AND
      METHODS: Lenalidomide was initiated at 2.5 mg/day and was escalated based on
      treatment tolerability to a maximum of 10 mg/day, for 21 days/cycle, for a
      maximum of seven cycles. Rituximab was administered at the end of cycle 1 and was
      continued for seven cycles. Patients received allopurinol and aspirin for
      prophylaxis. RESULTS: Sixty-nine patients enrolled onto one of two age-specific
      strata; patients' median age was 56 and 70 years for arms A and B, respectively.
      Patients in the older-patient stratum more frequently had elevated serum beta-2
      microglobulin levels, high-risk Rai stage, and were less likely to complete the
      maximum planned therapy. Adverse events were similar in the two arms.
      Nonhematologic toxicity was predominantly at grade 1/2, and neutropenia was the
      most common hematologic adverse event. The response rate for arm A was 95%, with
      20% complete responses (CRs) and 20% nodular partial responses. Of arm B
      patients, 78% achieved a response, of which 11% were CRs. Median progression-free
      survival (PFS) was 19 months for the younger cohort and 20 months for the older
      cohort. CONCLUSION: Intrapatient dose-escalation was safe. The majority of
      patients reached the maximum lenalidomide dose and experienced a response to a
      defined seven-cycle course of lenalidomide and rituximab therapy. Despite
      differences in baseline characteristics and the response rate between the two
      strata, the PFS did not differ.

PMID- 24868033
TI  - Suppression of Photosynthetic Gene Expression in Roots Is Required for Sustained
      Root Growth under Phosphate Deficiency.
AB  - Plants cope with inorganic phosphate (Pi) deficiencies in their environment by
      adjusting their developmental programs and metabolic activities. For Arabidopsis
      (Arabidopsis thaliana), the developmental responses include the inhibition of
      primary root growth and the enhanced formation of lateral roots and root hairs.
      Pi deficiency also inhibits photosynthesis by suppressing the expression of
      photosynthetic genes. Early studies showed that photosynthetic gene expression
      was also suppressed in Pi-deficient roots, a nonphotosynthetic organ; however,
      the biological relevance of this phenomenon remains unknown. In this work, we
      characterized an Arabidopsis mutant, hypersensitive to Pi starvation7 (hps7),
      that is hypersensitive to Pi deficiency; the hypersensitivity includes an
      increased inhibition of root growth. HPS7 encodes a tyrosylprotein
      sulfotransferase. Accumulation of HPS7 proteins in root tips is enhanced by Pi
      deficiency. Comparative RNA sequencing analyses indicated that the expression of
      many photosynthetic genes is activated in roots of hps7. Under Pi deficiency, the
      expression of photosynthetic genes in hps7 is further increased, which leads to
      enhanced accumulation of chlorophyll, starch, and sucrose. Pi-deficient hps7
      roots also produce a high level of reactive oxygen species. Previous research
      showed that the overexpression of GOLDEN-like (GLK) transcription factors in
      transgenic Arabidopsis activates photosynthesis in roots. The GLK overexpressing
      (GLK OX) lines also exhibit increased inhibition of root growth under Pi
      deficiency. The increased inhibition of root growth in hps7 and GLK OX lines by
      Pi deficiency was completely reversed by growing the plants in the dark. Based on
      these results, we propose that suppression of photosynthetic gene expression is
      required for sustained root growth under Pi deficiency.

PMID- 24868032
TI  - Hairy root transformation using Agrobacterium rhizogenes as a tool for exploring
      cell type-specific gene expression and function using tomato as a model.
AB  - Agrobacterium rhizogenes (or Rhizobium rhizogenes) is able to transform plant
      genomes and induce the production of hairy roots. We describe the use of A.
      rhizogenes in tomato (Solanum spp.) to rapidly assess gene expression and
      function. Gene expression of reporters is indistinguishable in plants transformed
      by Agrobacterium tumefaciens as compared with A. rhizogenes. A root cell type-
      and tissue-specific promoter resource has been generated for domesticated and
      wild tomato (Solanum lycopersicum and Solanum pennellii, respectively) using
      these approaches. Imaging of tomato roots using A. rhizogenes coupled with laser
      scanning confocal microscopy is facilitated by the use of a membrane-tagged
      protein fused to a red fluorescent protein marker present in binary vectors.
      Tomato-optimized isolation of nuclei tagged in specific cell types and
      translating ribosome affinity purification binary vectors were generated and used
      to monitor associated messenger RNA abundance or chromatin modification. Finally,
      transcriptional reporters, translational reporters, and clustered regularly
      interspaced short palindromic repeats-associated nuclease9 genome editing
      demonstrate that SHORT-ROOT and SCARECROW gene function is conserved between
      Arabidopsis (Arabidopsis thaliana) and tomato. 

PMID- 24868034
TI  - Constitutive production of nitric oxide leads to enhanced drought stress
      resistance and extensive transcriptional reprogramming in Arabidopsis.
AB  - Nitric oxide (NO) is involved in plant responses to many environmental stresses.
      Transgenic Arabidopsis lines that constitutively express rat neuronal NO synthase
      (nNOS) were described recently. In this study, it is reported that the nNOS
      transgenic Arabidopsis plants displayed high levels of osmolytes and increased
      antioxidant enzyme activities. Transcriptomic analysis identified 601 or 510
      genes that were differentially expressed as a consequence of drought stress or
      nNOS transformation, respectively. Pathway and gene ontology (GO) term enrichment
      analyses revealed that genes involved in photosynthesis, redox, stress, and
      phytohormone and secondary metabolism were greatly affected by the nNOS
      transgene. Several CBF genes and members of zinc finger gene families, which are
      known to regulate transcription in the stress response, were changed by the nNOS
      transgene. Genes regulated by both the nNOS transgene and abscisic acid (ABA)
      treatments were compared and identified, including those for two ABA receptors
      (AtPYL4 and AtPYL5). Moreover, overexpression of AtPYL4 and AtPYL5 enhanced
      drought resistance, antioxidant enzyme activity, and osmolyte levels. These
      observations increase our understanding of the role of NO in drought stress
      response in Arabidopsis. 

PMID- 24868036
TI  - Enhancing the productivity of grasses under high-density planting by engineering
      light responses: from model systems to feedstocks.
AB  - The successful commercialization of bioenergy grasses as lignocellulosic
      feedstocks requires that they be produced, processed, and transported
      efficiently. Intensive breeding for higher yields in food crops has resulted in
      varieties that perform optimally under high-density planting but often with high
      input costs. This is particularly true of maize, where most yield gains in the
      past have come through increased planting densities and an abundance of
      fertilizer. For lignocellulosic feedstocks, biomass rather than grain yield and
      digestibility of cell walls are two of the major targets for improvement.
      Breeding for high-density performance of lignocellulosic crops has been much less
      intense and thus provides an opportunity for improving the feedstock potential of
      these grasses. In this review, we discuss the role of vegetative shade on growth
      and development and suggest targets for manipulating this response to increase
      harvestable biomass under high-density planting. To engineer grass architecture
      and modify biomass properties at increasing planting densities, we argue that new
      model systems are needed and recommend Setaria viridis, a panicoid grass, closely
      related to major fuel and bioenergy grasses as a model genetic system. 

PMID- 24868035
TI  - Overexpression of pigeonpea stress-induced cold and drought regulatory gene
      (CcCDR) confers drought, salt, and cold tolerance in Arabidopsis.
AB  - A potent cold and drought regulatory protein-encoding gene (CcCDR) was isolated
      from the subtractive cDNA library of pigeonpea plants subjected to drought
      stress. CcCDR was induced by different abiotic stress conditions in pigeonpea.
      Overexpression of CcCDR in Arabidopsis thaliana imparted enhanced tolerance
      against major abiotic stresses, namely drought, salinity, and low temperature, as
      evidenced by increased biomass, root length, and chlorophyll content. Transgenic
      plants also showed increased levels of antioxidant enzymes, proline, and reducing
      sugars under stress conditions. Furthermore, CcCDR-transgenic plants showed
      enhanced relative water content, osmotic potential, and cell membrane stability,
      as well as hypersensitivity to abscisic acid (ABA) as compared with control
      plants. Localization studies confirmed that CcCDR could enter the nucleus, as
      revealed by intense fluorescence, indicating its possible interaction with
      various nuclear proteins. Microarray analysis revealed that 1780 genes were up
      regulated in CcCDR-transgenics compared with wild-type plants. Real-time PCR
      analysis on selected stress-responsive genes, involved in ABA-dependent and 
      independent signalling networks, revealed higher expression levels in transgenic
      plants, suggesting that CcCDR acts upstream of these genes. The overall results
      demonstrate the explicit role of CcCDR in conferring multiple abiotic stress
      tolerance at the whole-plant level. The multifunctional CcCDR seems promising as
      a prime candidate gene for enhancing abiotic stress tolerance in diverse plants. 

PMID- 24868037
TI  - Cell-autonomous-like silencing of GFP-partitioned transgenic Nicotiana
      benthamiana.
AB  - We previously reported the novel partitioning of regional GFP-silencing on leaves
      of 35S-GFP transgenic plants, coining the term "partitioned silencing". We set
      out to delineate the mechanism of partitioned silencing. Here, we report that the
      partitioned plants were hemizygous for the transgene, possessing two direct
      repeat copies of 35S-GFP. The detection of both siRNA expression (21 and 24 nt)
      and DNA methylation enrichment specifically at silenced regions indicated that
      both post-transcriptional gene silencing (PTGS) and transcriptional gene
      silencing (TGS) were involved in the silencing mechanism. Using in vivo
      agroinfiltration of 35S-GFP/GUS and inoculation of TMV-GFP RNA, we demonstrate
      that PTGS, not TGS, plays a dominant role in the partitioned silencing,
      concluding that the underlying mechanism of partitioned silencing is analogous to
      RNA-directed DNA methylation (RdDM). The initial pattern of partitioned silencing
      was tightly maintained in a cell-autonomous manner, although partitioned-silenced
      regions possess a potential for systemic spread. Surprisingly, transcriptome
      profiling through next-generation sequencing demonstrated that expression levels
      of most genes involved in the silencing pathway were similar in both GFP
      expressing and silenced regions although a diverse set of region-specific
      transcripts were detected.This suggests that partitioned silencing can be
      triggered and regulated by genes other than the genes involved in the silencing
      pathway. 

PMID- 24868039
TI  - Molecular interaction of jasmonate and phytochrome A signalling.
AB  - The phytochrome family of red (R) and far-red (FR) light receptors (phyA-phyE in
      Arabidopsis) play important roles throughout plant development and regulate
      elongation growth during de-etiolation and under light. Phytochromes regulate
      growth through interaction with the phytohormones gibberellin, auxin, and
      brassinosteroid. Recently it has been established that jasmonic acid (JA), a
      phytohormone for stress responses, namely wounding and defence, is also important
      in inhibition of hypocotyl growth regulated by phyA and phyB. This review focuses
      on recent advances in our understanding of the molecular basis of the interaction
      between JA and phytochrome signalling particularly during seedling development in
      Arabidopsis. Significantly, JA biosynthesis genes are induced by phyA. The
      protein abundance of JAR1/FIN219, an enzyme for the final synthesis step to give
      JA-Ile, an active form of JA, is also determined by phyA. In addition,
      JAR1/FIN219 directly interacts with an E3-ligase, COP1, a master regulator for
      transcription factors regulating hypocotyl growth, suggesting a more direct role
      in growth regulation. There are a number of points of interaction in the
      molecular signalling of JA and phytochrome during seedling development in
      Arabidopsis, and we propose a model for how they work together to regulate
      hypocotyl growth. 

PMID- 24868038
TI  - Linking chlorophyll a fluorescence to photosynthesis for remote sensing
      applications: mechanisms and challenges.
AB  - Chlorophyll a fluorescence (ChlF) has been used for decades to study the
      organization, functioning, and physiology of photosynthesis at the leaf and
      subcellular levels. ChlF is now measurable from remote sensing platforms. This
      provides a new optical means to track photosynthesis and gross primary
      productivity of terrestrial ecosystems. Importantly, the spatiotemporal and
      methodological context of the new applications is dramatically different compared
      with most of the available ChlF literature, which raises a number of important
      considerations. Although we have a good mechanistic understanding of the
      processes that control the ChlF signal over the short term, the seasonal link
      between ChlF and photosynthesis remains obscure. Additionally, while the current
      understanding of in vivo ChlF is based on pulse amplitude-modulated (PAM)
      measurements, remote sensing applications are based on the measurement of the
      passive solar-induced chlorophyll fluorescence (SIF), which entails important
      differences and new challenges that remain to be solved. In this review we
      introduce and revisit the physical, physiological, and methodological factors
      that control the leaf-level ChlF signal in the context of the new remote sensing
      applications. Specifically, we present the basis of photosynthetic acclimation
      and its optical signals, we introduce the physical and physiological basis of
      ChlF from the molecular to the leaf level and beyond, and we introduce and
      compare PAM and SIF methodology. Finally, we evaluate and identify the challenges
      that still remain to be answered in order to consolidate our mechanistic
      understanding of the remotely sensed SIF signal. 

PMID- 24868040
TI  - Editor's briefing.

PMID- 24868041
TI  - Time to put patients first by investing in general practice.

PMID- 24868042
TI  - The future of general practice in China: from 'barefoot doctors' to GPs?

PMID- 24868043
TI  - Boost or burden? Issues posed by short placements in resource-poor settings.

PMID- 24868044
TI  - RCGP Continuity of Care Toolkit: promoting relational continuity [corrected].

PMID- 24868046
TI  - What did the questionnaire say?

PMID- 24868048
TI  - Assessment of risk communication.

PMID- 24868047
TI  - Authors' response.

PMID- 24868049
TI  - Communicating risk.

PMID- 24868050
TI  - In general practice, doctors record higher blood pressures in the presence of
      students.

PMID- 24868051
TI  - White coat hypertension: is it all just in the look?

PMID- 24868052
TI  - The effect of clinical inertia on the management of blood pressure.

PMID- 24868054
TI  - Viewpoint: Is our profession in need of occupational therapy?

PMID- 24868055
TI  - Palestine: a week in November.

PMID- 24868056
TI  - RCGP Junior International Committee: a global approach to primary care.

PMID- 24868057
TI  - How disability can win England the World Cup.

PMID- 24868058
TI  - Yonder: Grandparenthood, rural health, diabetes, & perinatal psychiatry.

PMID- 24868059
TI  - Is the 'scandal' of diabetes care in general practice fact or fiction?

PMID- 24868061
TI  - An A-Z of medical philosophy: R is for Realism--is our knowledge real or all in
      the mind?

PMID- 24868062
TI  - Fyi ....

PMID- 24868063
TI  - William Pickles Lecture 2013: For they are born for another time.

PMID- 24868064
TI  - Just stick to the facts: remember Goodhart's law.

PMID- 24868065
TI  - Research into practice: acutely ill children.

PMID- 24868066
TI  - Diagnosis and management of varicose veins in the legs: NICE guideline.

PMID- 24868067
TI  - Side effects of compression stockings: a case report.

PMID- 24868068
TI  - Attitudes towards domestic violence in Lebanon: a qualitative study of primary
      care practitioners.
AB  - BACKGROUND: Domestic violence (DV) is highly prevalent in the developing and
      developed world. Healthcare systems internationally are still not adequately
      addressing the needs of patients experiencing violence. AIM: To explore
      physicians' attitudes about responding to DV, their perception of the physician's
      role, and the factors that influence their response. DESIGN AND SETTING:
      Qualitative study using individual interviews among primary care practitioners
      working in Lebanon. METHOD: Primary care clinicians practising for >5 years and
      with >100 patient consultations a week were interviewed. Physicians were asked
      about their practice when encountering women disclosing abuse, their opinion
      about the engagement of the health services with DV, their potential role, and
      the anticipated reaction of patients and society to this extended role. RESULTS:
      Physicians felt that they were well positioned to play a pivotal role in
      addressing DV; yet they had concerns related to personal safety, worry about
      losing patients, and opposing the norms of a largely conservative society.
      Several physicians justified DV or blamed the survivor rather than the
      perpetrator for triggering the violent behaviour. Moreover, religion was
      perceived as sanctioning DV. CONCLUSION: Perceived cultural norms and religious
      beliefs seem to be major barriers to physicians responding to DV in Lebanon, and
      possibly in the Arab world more generally. Financial concerns also need to be
      addressed to encourage physicians to address DV.

PMID- 24868069
TI  - The inverse primary care law in sub-Saharan Africa: a qualitative study of the
      views of migrant health workers.
AB  - BACKGROUND: Many low-income and middle-income countries globally are now pursuing
      ambitious plans for universal primary care, but are failing to deliver adequate
      care quality because of intractable human resource problems. AIM: To understand
      why migrant nurses and doctors from sub-Saharan Africa did not wish to take up
      available posts in primary and first-contact care in their home countries. DESIGN
      AND SETTING: Qualitative study of migrant health workers to Europe (UK, Belgium,
      and Austria) or southern Africa (Botswana and South Africa) from sub-Saharan
      Africa. METHOD: Semi-structured interviews with 66 health workers (24 nurses and
      42 doctors) from 18 countries between July 2011 and April 2012. Transcripts were
      analysed thematically using a framework approach. RESULTS: The reasons given for
      choosing not to work in primary care were grouped into three main analytic
      streams: poor working environment, difficult living experiences, and poor career
      path. Responders described a lack of basic medicines and equipment, an
      unmanageable workload, and lack of professional support. Many had concerns about
      personal security, living conditions (such as education for children), and poor
      income. Primary care was seen as lower status than hospital medicine, with lack
      of specialist training opportunities and more exposure to corruption.
      CONCLUSIONS: Clinicians are reluctant to work in the conditions they currently
      experience in primary care in sub-Saharan Africa and these conditions tend to get
      worse as poverty and need for primary care increases. This inverse primary care
      law undermines achievement of universal health coverage. Policy experience from
      countries outside Africa shows that it is not immutable.

PMID- 24868070
TI  - Making short-term international medical volunteer placements work: a qualitative
      study.
AB  - BACKGROUND: International medical volunteering has grown in recent decades. It
      has the potential to benefit and harm the volunteer and host countries; but there
      is a paucity of literature on the impacts of international medical volunteering
      and a need to find ways to optimise the benefits of such placements. AIM: In this
      study, one example of international medical volunteering was examined involving
      British GPs on short-term placements in Nepal. The intention was to explore the
      expectations and experiences of the local health workers, volunteers, and host
      organisation to try and understand what makes volunteer placements work. DESIGN:
      Qualitative study of key informant interviews. SETTING: Stakeholders of a short
      term international medical volunteer (IMV) placement programme in Nepal. METHOD:
      Key informant interviews were carried out via face-to-face or telephone/internet
      interviews with five previous volunteers, three representatives from a non
      governmental organisation providing placements, and five local health workers in
      Nepal who had had contact with the IMVs. Interviews were recorded, transcribed,
      and analysed using standard thematic framework approaches. RESULTS: All the
      stakeholders had their own specific motives for participating in the IMV
      programme. The relationship between volunteers and the Nepalese health workers
      was complex and characterised by discrepant and occasionally unrealistic
      expectations. Managing these different expectations was challenging. CONCLUSION:
      Contextual issues and cultural differences are important considerations in
      medical volunteer programmes, and this study highlights the importance of robust
      preparation pre-placement for the volunteer and host to ensure positive outcomes.

PMID- 24868071
TI  - Undergraduate teaching in UK general practice: a geographical snapshot.
AB  - BACKGROUND: Learning in general practice is an essential component of
      undergraduate medical education; currently, on average, 13% of clinical
      placements in the UK are in general practice. However, whether general practice
      can sustainably deliver more undergraduate placements is uncertain. AIM: To
      identify the geographical distribution of undergraduate teaching practices and
      their distance from the host medical school. DESIGN AND SETTING: National survey
      of all medical schools in the UK. METHOD: All 33 UK medical schools were invited
      to provide the postcodes of their undergraduate teaching practices. These were
      collated, de-duplicated, and mapped. The distance in kilometres and journey times
      by car and public transport between each medical school and its teaching
      practices was estimated using Transport Direct (www.transportdirect.info). The
      postcodes of every practice in the UK were obtained from the UK's health
      departments. RESULTS: All 33 UK medical schools responded; 4392 practices
      contributed to teaching, with a median (minimum-maximum) of 142 (17-385)
      practices per school. The median (minimum-maximum) distance between a school and
      a teaching practice was 28 km (0-1421 km), 41 (0:00-23:26) minutes' travel by car
      and 1 hour 12 (0:00-17:29) minutes' travel by public transport. All teaching
      practices were accessible by public transport in one school and 90-99% were in a
      further four schools; 24 schools had >20% of practices that were inaccessible by
      public transport. CONCLUSION: The 4392 undergraduate teaching general practices
      are widely distributed and potentially any practice, no matter how isolated,
      could contribute to undergraduate education. However, this is, at the price of a
      considerable travel burden.

PMID- 24868072
TI  - Predictive values of GPs' suspicion of serious disease: a population-based follow
      up study.
AB  - BACKGROUND: Knowledge is sparse on the prevalence of suspicion of cancer and
      other serious diseases in general practice. Likewise, little is known about the
      possible implications of this suspicion on future healthcare use and diagnoses.
      AIM: To study the prevalence of GPs' suspicions of cancer or other serious
      diseases and analyse how this suspicion predicted the patients' healthcare use
      and diagnoses of serious disease. DESIGN AND SETTING: Prospective population
      based cohort study of 4518 patients consulting 404 GPs in a mix of urban, semi
      urban and rural practices in Central Denmark Region during 2008-2009. METHOD: The
      GPs registered consultations in 1 work day, including information on their
      suspicion of the presence of cancer or another serious disease. The patients were
      followed up for use of healthcare services and new diagnoses through the use of
      national registers. RESULTS: Prevalence of suspicion was 5.7%. Suspicion was
      associated with an increase in referrals (prevalence ratio [PR] = 2.56, 95%
      confidence interval [CI] = 2.22 to 2.96), especially for diagnostic imaging (PR =
      3.95, 95% CI = 2.80 to 5.57), increased risk of a new diagnosis of cancer or
      another serious disease within 2 months (hazard ratio [HR] = 2.98, 95% CI = 1.93
      to 4.62)--especially for cancer (HR = 7.55, 95% CI = 2.66 to 21.39)--and
      increased use of general practice (relative risk [RR] = 1.14, 95% CI = 1.06 to
      1.24) and hospital visits (RR = 1.90, 95% CI = 1.62 to 2.23). The positive
      predictive value of a GP suspicion was 9.8% (95% CI = 6.4 to 14.1) for cancer or
      another serious disease within 2 months. CONCLUSION: A GP suspicion of serious
      disease warrants further investigation, and the organisation of the healthcare
      system should ensure direct access from the primary sector to specialised tests.

PMID- 24868073
TI  - Using a patient-generated mental-health measure 'PSYCHLOPS' to explore problems
      in patients with coronary heart disease.
AB  - BACKGROUND: Patients with coronary heart disease (CHD) who are depressed have an
      increased risk of further cardiac events and higher mortality. AIM: To use a
      patient generated instrument (PSYCHLOPS) to define categories of concerns in
      patients with CHD. To define the psychometric characteristics of patients in each
      category. DESIGN AND SETTING: Cross-sectional study set in general practices in
      south London. METHOD: Of 3325 patients on the CHD registers in 15 general
      practices, 655 completed six baseline psychometric and functional instruments:
      PSYCHLOPS, HADS-Depression, HADS-Anxiety, Clinical Interview Schedule-Revised,
      SF12-Mental and SF12-Physical. Content analysis was used to categorise patients
      based on their main problem, as elicited by PSYCHLOPS. Mean psychometric scores
      were adjusted for confounding by age, sex, deprivation and ethnicity and
      calculated for each response category. RESULTS: Response categories were:
      physical problems, both non-cardiac (23.2%) and cardiac (6.0%); social problems:
      relationship/family (18.2%), money (7.5%), work (3.1%); functional (9.8%);
      psychological (6.9%); miscellaneous (7.3%); 'no problem' (18.2%). The highest
      psychological distress scores were found in 'physical, cardiac' and
      'psychological' categories. The 'no problem' category had significantly lower
      psychological distress and higher functional capacity than other categories.
      CONCLUSIONS: PSYCHLOPS enabled the identification of subtypes of CHD patients,
      based on a classification of self-reported problems. A high proportion of CHD
      patients report social problems. Psychological distress was highest in those
      reporting cardiac or psychological symptoms. Services should be aligned to the
      reported needs of patients.

PMID- 24868076
TI  - Primary care in Asia: a call for compulsory vocational training.

PMID- 24868075
TI  - Increasing awareness of gynaecological cancer symptoms: a GP perspective.
AB  - BACKGROUND: In the UK there has been an effort, through the National Awareness
      and Early Diagnosis Initiative (NAEDI), to increase early stage diagnoses and
      ultimately cancer survival. Encouraging early symptom presentation through
      awareness-raising activities in primary care is one method to achieve this goal.
      Understanding GPs' views about this type of activity, however, is crucial prior
      to implementation. AIM: To describe GPs' attitudes to raising public awareness of
      gynaecological cancers, and their views about the potential impact on primary
      care services. DESIGN AND SETTING: An online survey with a convenience sample
      recruited from 1860 UK general practices. METHOD: An invitation was emailed to
      GPs via practice managers and included a weblink to a draft education leaflet and
      an online survey about the impact of sending a leaflet giving information about
      symptoms associated with gynaecological cancers to all women on GPs' lists.
      Participants could offer additional free text comments which were coded using
      content analysis. RESULTS: A total of 621 GPs participated. Most (77%, 477) felt
      that raising awareness of cancers was important. Only half (50%, 308), however,
      indicated that they would distribute such a leaflet from their practice. Barriers
      to implementation included concerns about financial costs; emotional impact on
      patients; increased demand for appointments and diagnostic services, such as
      ultrasound. CONCLUSIONS: GPs were generally positive about an intervention to
      improve patients' awareness of gynaecological cancers, but had concerns about
      increasing rates of presentation. There is a need for research quantifying the
      benefits of earlier diagnosis against resource costs such as increased
      consultations, investigations, and referrals.

PMID- 24868074
TI  - How users of indwelling urinary catheters talk about sex and sexuality: a
      qualitative study.
AB  - BACKGROUND: An indwelling urinary catheter can solve the problem of incontinence
      and may be life-saving in individuals with retention, but it can cause problems
      such as infection and may have a negative impact on body image, sex, and
      sexuality. AIM: To explore the individual's perceptions of how a long-term
      urinary catheter can affect body image, sex, and sexuality; and to help GPs to
      discuss the subject in consultations. DESIGN AND SETTING: Qualitative study of a
      diverse sample of individuals living with a long-term urinary catheter.
      Interviews took place all over the UK, usually in the individuals' homes. METHOD:
      Narrative interviews were audiorecorded, transcribed, and analysed thematically,
      using the constant comparative method. RESULTS: Some individuals said that sex
      was not an important part of their lives because of old age, illness, or the
      catheter. Others talked about how their catheter and their disability affected
      their sexual self-esteem, feelings of masculinity or femininity, and how the
      catheter caused pain, discomfort, or unexpected symptoms during sex. Many noted
      the lack of information on the subject and also said that health professionals
      were reluctant to talk about sex. For a minority a catheter was not a major
      problem in relation to sex. CONCLUSION: Some individuals using a urinary catheter
      would benefit from information on how to have a sexual relationship with a
      catheter in place and a chance to discuss the subject with their doctors. GPs
      need to be aware that sex may matter to a person with a catheter and how illness,
      disability, and a catheter may affect sexuality.

PMID- 24868077
TI  - Paraneoplastic thrombocytosis: the secrets of tumor self-promotion.
AB  - Paraneoplastic thrombocytosis is associated with many solid tumors and often
      correlates with reduced survival. Recent studies suggest that a pathogenic feed
      back loop may be operative between platelets and tumor cells, with reciprocal
      interactions between tumor growth/metastasis and thrombocytosis/platelet
      activation. Specific molecular pathways have been identified in which tumors can
      stimulate platelet production and activation; activated platelets can, in turn,
      promote tumor growth and metastasis. Taken together, these findings provide
      exciting new potential targets for therapeutic intervention. 

PMID- 24868079
TI  - The behavior of Turkish cancer patients in fasting during the holy month of
      Ramadan.
AB  - OBJECTIVE: Fasting during the holy month of Ramadan is one of the major
      obligations for all adult Muslims. We performed a survey of Turkish Muslim cancer
      patients to examine the extent of their fasting status and to compare various
      clinical characteristics of fasting and non-fasting cancer patients during the
      month of Ramadan. METHODS: This study was conducted on 701 adult cancer patients
      who attended ambulatory patient care units answered the questionnaires. RESULTS:
      The population comprised 445 women (63.5%), and the median age was 54 years.
      Before diagnosis of cancer, 93.1% of the patients used fast consists of
      completely (78.3%) and partial (14.8%). However, 15% of cases were fasting on the
      day of interview, either partially (7.4%) or completely (7.6%) with equal
      distributions. Patients who were females, those with good performance status,
      those without any comorbid disease, who had non-metastatic disease, those with
      history of surgery, those treated with radiotherapy and those being treated with
      oral chemotherapeutic agents were more likely to be fasting than others. The
      fasting ones had more prevalent among patients with lymphoma, urogenital cancer
      and breast cancer; conversely, the rate of fasting status among patients with
      lung and gastrointestinal cancer was quite low. Only 20.8% of all patients asked
      their physician whether it was alright for them to fast and physicians generally
      had a negative attitude towards fasting (83.2%). CONCLUSIONS: Majority of cancer
      patients are not fasting during the month of Ramadan, and a small part of
      patients consult this situation to their physician.

PMID- 24868081
TI  - Keyhole surgery at Maidstone hospital raised "serious concerns," finds review.

PMID- 24868078
TI  - Validation of ZAP-70 methylation and its relative significance in predicting
      outcome in chronic lymphocytic leukemia.
AB  - ZAP-70 methylation 223 nucleotides downstream of transcription start (CpG+223)
      predicts outcome in chronic lymphocytic leukemia (CLL), but its impact relative
      to CD38 and ZAP-70 expression or immunoglobulin heavy chain variable region
      (IGHV) status is uncertain. Additionally, standardizing ZAP-70 expression
      analysis has been unsuccessful. CpG+223 methylation was quantitatively determined
      in 295 untreated CLL cases using MassARRAY. Impact on clinical outcome vs CD38
      and ZAP-70 expression and IGHV status was evaluated. Cases with low methylation
      (<20%) had significantly shortened time to first treatment (TT) and overall
      survival (OS) (P < .0001). For TT, low methylation defined a large subset of ZAP
      70 protein-negative cases with significantly shortened TT (median, 8.0 vs 3.9
      years for high vs low methylation; hazard ratio [HR] = 0.43; 95% confidence
      interval [CI], 0.25-0.74). Conversely, 16 ZAP-70 protein-positive cases with high
      methylation had poor outcome (median, 1.1 vs 2.3 years for high vs low
      methylation; HR = 1.62; 95% CI, 0.87-3.03). For OS, ZAP-70 methylation was the
      strongest risk factor; CD38 and ZAP-70 expression or IGHV status did not
      significantly improve OS prediction. A pyrosequencing assay was established that
      reproduced the MassARRAY data (kappa coefficient > 0.90). Thus, ZAP-70 CpG+223
      methylation represents a superior biomarker for TT and OS that can be feasibly
      measured, supporting its use in risk-stratifying CLL. 

PMID- 24868080
TI  - A phase I study of split-dose cisplatin and etoposide with concurrent accelerated
      hyperfractionated thoracic radiotherapy in elderly patients with limited-disease
      small cell lung cancer.
AB  - OBJECTIVE: The optimal treatment for elderly patients with limited-disease small
      cell lung cancer has not been defined. We therefore performed a Phase I study for
      split-dose cisplatin plus etoposide combined with early concurrent accelerated
      hyperfractionated thoracic radiotherapy in elderly (70 years of age or older)
      patients with limited-disease small cell lung cancer. METHODS: Chemotherapy
      consisted of cisplatin at 20 or 25 mg/m(2) and etoposide at 80 mg/m(2), both
      administered on Days 1-3 of a 28-day cycle. Radiotherapy was initiated at the
      onset of chemotherapy and administered at a dose of 1.5 Gy twice daily over 3
      weeks up to a total dose of 45 Gy. RESULTS: Twelve patients with a median age of
      76 years (range, 70-85) were enrolled. Dose-limiting toxicities occurred in two
      (hyponatremia of Grade 4 or cardiac ischemia of Grade 3) of the six patients
      treated at dose Level 1 as well as in three (perforation of the sigmoid colon of
      Grade 3, febrile neutropenia of Grade 3, or hyponatremia of Grade 3) of the six
      patients treated at dose Level 2. The most frequent non-hematologic adverse
      events included anorexia, fatigue, esophagitis and pneumonitis, but most of these
      events were of Grade 1 or 2. CONCLUSIONS: The recommended dose for cisplatin and
      etoposide chemotherapy administered on Days 1-3 was determined to be 20 and 80
      mg/m(2), respectively. Our results indicate that split-dose cisplatin plus
      etoposide chemotherapy combined with early concurrent accelerated
      hyperfractionated thoracic radiotherapy is well tolerated by elderly patients
      with limited-disease small cell lung cancer. CLINICAL TRIALS REGISTRATION NO:
      UMIN Clinical Trials Registry (UMIN-CTR) C000000143.

PMID- 24868082
TI  - A woman with a sore spot on her leg.

PMID- 24868084
TI  - Fixed dose combinations of cardiovascular drugs.

PMID- 24868083
TI  - Effect of fixed dose combination treatment on adherence and risk factor control
      among patients at high risk of cardiovascular disease: randomised controlled
      trial in primary care.
AB  - OBJECTIVE: To evaluate whether provision of fixed dose combination treatment
      improves adherence and risk factor control compared with usual care of patients
      at high risk of cardiovascular disease in primary care. DESIGN: Open label
      randomised control trial: IMPACT (IMProving Adherence using Combination Therapy).
      SETTING: 54 general practices in the Auckland and Waikato regions of New Zealand,
      July 2010 to August 2013. PARTICIPANTS: 513 adults (including 257 indigenous
      Maori) at high risk of cardiovascular disease (established cardiovascular disease
      or five year risk >= 15%) who were recommended for treatment with antiplatelet,
      statin, and two or more blood pressure lowering drugs. 497 (97%) completed 12
      months' follow-up. INTERVENTIONS: Participants were randomised to continued usual
      care or to fixed dose combination treatment (with two versions available: aspirin
      75 mg, simvastatin 40 mg, and lisinopril 10 mg with either atenolol 50 mg or
      hydrochlorothiazide 12.5 mg). All drugs in both treatment arms were prescribed by
      their usual general practitioners and dispensed by local community pharmacists.
      MAIN OUTCOME MEASURES: Primary outcomes were self reported adherence to
      recommended drugs (antiplatelet, statin, and two or more blood pressure lowering
      agents) and mean change in blood pressure and low density lipoprotein cholesterol
      at 12 months. RESULTS: Adherence to all four recommended drugs was greater among
      fixed dose combination than usual care participants at 12 months (81% v 46%;
      relative risk 1.75, 95% confidence interval 1.52 to 2.03, P<0.001; number needed
      to treat 2.9, 95% confidence interval 2.3 to 3.7). Adherence for each drug type
      at 12 months was high in both groups but especially in the fixed dose combination
      group: for antiplatelet treatment it was 93% fixed dose combination v 83% usual
      care (P<0.001), for statin 94% v 89% (P=0.06), for combination blood pressure
      lowering 89% v 59% (P<0.001), and for any blood pressure lowering 96% v 91%
      (P=0.02). Self reported adherence was highly concordant with dispensing data
      (dispensing of all four recommended drugs 79% fixed dose combination v 47% usual
      care, relative risk 1.67, 95% confidence interval 1.44 to 1.93, P<0.001). There
      was no statistically significant improvement in risk factor control between the
      fixed dose combination and usual care groups over 12 months: the difference in
      systolic blood pressure was -2.2 mm Hg (-4.5 v -2.3, 95% confidence interval -5.6
      to 1.2, P=0.21), in diastolic blood pressure -1.2 mm Hg (-2.1 v -0.9, -3.2 to
      0.8, P=0.22) and in low density lipoprotein cholesterol -0.05 mmol/L (-0.20 v 
      0.15, -0.17 to 0.08, P=0.46). The number of participants with cardiovascular
      events or serious adverse events was similar in both treatment groups (fixed dose
      combination 16 v usual care 18 (P=0.73), 99 v 93 (P=0.56), respectively). Fixed
      dose combination treatment was discontinued in 94 participants (37%). The most
      commonly reported reason for discontinuation was a side effect (54/75, 72%).
      Overall, 89% (227/256) of fixed dose combination participants' general
      practitioners completed a post-trial survey, and the fixed dose combination
      strategy was rated as satisfactory or very satisfactory for starting treatment
      (206/227, 91%), blood pressure control (180/220, 82%), cholesterol control
      (170/218, 78%), tolerability (181/223, 81%), and prescribing according to local
      guidelines (185/219, 84%). When participants were asked at 12 months how easy
      they found taking their prescribed drugs, most responded very easy or easy
      (224/246, 91% fixed dose combination v 212/246, 86% usual care, P=0.09). At 12
      months the change in other lipid fractions, difference in EuroQol-5D, and
      difference in barriers to adherence did not differ significantly between the
      treatment groups. CONCLUSIONS: Among this well treated primary care population,
      fixed dose combination treatment improved adherence to the combination of all
      recommended drugs but improvements in clinical risk factors were small and did
      not reach statistical significance. Acceptability was high for both general
      practitioners and patients, although the discontinuation rate was high. TRIAL
      REGISTRATION: Australian New Zealand Clinical Trial Registry ACTRN12606000067572.

PMID- 24868085
TI  - Online restaurant reviews identify outbreaks of undetected foodborne illness.

PMID- 24868086
TI  - Scottish independence could threaten medical research, warn scientists.

PMID- 24868087
TI  - The Cebpa +37-kb enhancer directs transgene expression to myeloid progenitors and
      to long-term hematopoietic stem cells.
AB  - C/EBPalpha is expressed preferentially in myeloid compared with lymphoid or
      erythroid cells and directs myeloid lineage specification. C/EBPalpha is also
      expressed at lower levels in HSCs and in several nonhematopoietic tissues. The
      Cebpa gene has a conserved, 450-bp segment at +37 kb that harbors enhancer
      specific epigenetic marks and is activate in a myeloid cell line. Herein, we
      characterize transgenic C57BL/6 mice, in which the Cebpa enhancer and 845-bp
      promoter regulate a hCD4 reporter. FACS analysis, in vitro colony assays, and in
      vivo competitive and secondary transplantation revealed that myeloid but not MEPs
      or lymphoid progenitors and also functional LT-HSCs are found almost exclusively
      in the Cebpa-hCD4(+) compared with hCD4(-) marrow population. hCD4(+) CMP yielded
      predominantly myeloid, whereas hCD4(-) CMP generated mainly Meg/E colonies.
      Providing insight into control of CMP maturation, Cebpa and Pu.1 RNAs were
      preferentially expressed in hCD4(+) CMP, Scl, Gata2, Gata1, Klf1, Ets1, and Fli1
      predominated in hCD4(-) CMP, and Runx1, Myb, HoxA9, and Erg levels were similar
      in both. Cebpa-hCD4 transgene expression was lacking in multiple nonhematopoietic
      tissues. In summary, the +37-kb Cebpa enhancer and promoter are sufficient for
      marrow myeloid progenitor and LT-HSC-specific expression. 

PMID- 24868088
TI  - Phagosome maturation in polarized macrophages.
AB  - Macrophages are capable of assuming distinct, meta-stable, functional phenotypes
      in response to environmental cues-a process referred to as macrophage
      polarization. The identity and plasticity of polarized macrophage subsets as well
      as their functions in the maintenance of homeostasis and the progression of
      various pathologies have become areas of intense interest. Yet, the mechanisms by
      which they achieve subset-specific functions at the cellular level remain
      unclear. It is becoming apparent that phagocytosis and phagosome maturation
      differ depending on the polarization of macrophages. This minireview summarizes
      recent progress in this field, highlighting developing trends and discussing the
      molecular mechanisms that underlie subset-specific functions. 

PMID- 24868090
TI  - Record 5 million UK children expected to be living in poverty by 2020.

PMID- 24868091
TI  - Novel drug combination for tuberculosis to be tested across 50 sites.

PMID- 24868092
TI  - Statins for primary prevention of cardiovascular disease.

PMID- 24868089
TI  - At the Bench: Helicobacter pylori, dysregulated host responses, DNA damage, and
      gastric cancer.
AB  - Helicobacter pylori infection is the strongest known risk factor for the
      development of gastric cancer. Given that ~50% of the global population is
      infected with this pathogen, there is great impetus to elucidate underlying
      causes that mediate progression from infection to cancer. Recent evidence
      suggests that H. pylori-induced chronic inflammation and oxidative stress create
      an environment conducive to DNA damage and tissue injury. DNA damage leads to
      genetic instability and eventually, neoplastic transformation. Pathogen-encoded
      virulence factors induce a robust but futile immune response and alter host
      pathways that lower the threshold for carcinogenesis, including DNA damage
      repair, polyamine synthesis and catabolism, antioxidant responses, and cytokine
      production. Collectively, such dysregulation creates a protumorigenic
      microenvironment within the stomach. This review seeks to address each of these
      aspects of H. pylori infection and to call attention to areas of particular
      interest within this field of research. This review also seeks to prioritize
      areas of translational research related to H. pylori-induced gastric cancer based
      on insights garnered from basic research in this field. See related review by
      Dalal and Moss, At the Bedside: H. pylori, dysregulated host responses, DNA
      damage, and gastric cancer. 

PMID- 24868094
TI  - Lipidomics identifies a requirement for peroxisomal function during influenza
      virus replication.
AB  - Influenza virus acquires a host-derived lipid envelope during budding, yet a
      convergent view on the role of host lipid metabolism during infection is lacking.
      Using a mass spectrometry-based lipidomics approach, we provide a systems-scale
      perspective on membrane lipid dynamics of infected human lung epithelial cells
      and purified influenza virions. We reveal enrichment of the minor peroxisome
      derived ether-linked phosphatidylcholines relative to bulk ester-linked
      phosphatidylcholines in virions as a unique pathogenicity-dependent signature for
      influenza not found in other enveloped viruses. Strikingly, pharmacological and
      genetic interference with peroxisomal and ether lipid metabolism impaired
      influenza virus production. Further integration of our lipidomics results with
      published genomics and proteomics data corroborated altered peroxisomal lipid
      metabolism as a hallmark of influenza virus infection in vitro and in vivo.
      Influenza virus may therefore tailor peroxisomal and particularly ether lipid
      metabolism for efficient replication.

PMID- 24868093
TI  - High confidence proteomic analysis of yeast LDs identifies additional droplet
      proteins and reveals connections to dolichol synthesis and sterol acetylation.
AB  - Accurate protein inventories are essential for understanding an organelle's
      functions. The lipid droplet (LD) is a ubiquitous intracellular organelle with
      major functions in lipid storage and metabolism. LDs differ from other organelles
      because they are bounded by a surface monolayer, presenting unique features for
      protein targeting to LDs. Many proteins of varied functions have been found in
      purified LD fractions by proteomics. While these studies have become increasingly
      sensitive, it is often unclear which of the identified proteins are specific to
      LDs. Here we used protein correlation profiling to identify 35 proteins that
      specifically enrich with LD fractions of Saccharomyces cerevisiae Of these
      candidates, 30 fluorophore-tagged proteins localize to LDs by microscopy,
      including six proteins, several with human orthologs linked to diseases, which we
      newly identify as LD proteins (Cab5, Rer2, Say1, Tsc10, YKL047W, and YPR147C).
      Two of these proteins, Say1, a sterol deacetylase, and Rer2, a cis-isoprenyl
      transferase, are enzymes involved in sterol and polyprenol metabolism,
      respectively, and we show their activities are present in LD fractions. Our
      results provide a highly specific list of yeast LD proteins and reveal that the
      vast majority of these proteins are involved in lipid metabolism.

PMID- 24868095
TI  - Critical role of neutral cholesteryl ester hydrolase 1 in cholesteryl ester
      hydrolysis in murine macrophages.
AB  - Hydrolysis of intracellular cholesteryl ester (CE) is the rate-limiting step in
      the efflux of cholesterol from macrophage foam cells. In mouse peritoneal
      macrophages (MPMs), this process is thought to involve several enzymes: hormone
      sensitive lipase (Lipe), carboxylesterase 3 (Ces3), neutral CE hydrolase 1
      (Nceh1). However, there is some disagreement over the relative contributions of
      these enzymes. To solve this problem, we first compared the abilities of several
      compounds to inhibit the hydrolysis of CE in cells overexpressing Lipe, Ces3, or
      Nceh1. Cells overexpressing Ces3 had negligible neutral CE hydrolase activity. We
      next examined the effects of these inhibitors on the hydrolysis of CE and
      subsequent cholesterol trafficking in MPMs. CE accumulation was increased by a
      selective inhibitor of Nceh1, paraoxon, and two nonselective inhibitors of Nceh1,
      (+)-AS115 and (-)-AS115, but not by two Lipe-selective inhibitors, orlistat and
      76-0079. Paraoxon inhibited cholesterol efflux to apoA-I or HDL, while 76-0079
      did not. These results suggest that Nceh1 plays a dominant role over Lipe in the
      hydrolysis of CE and subsequent cholesterol efflux in MPMs. 

PMID- 24868097
TI  - What should we die from?

PMID- 24868096
TI  - Development and validation of sensitive LC-MS/MS assays for quantification of HP
      beta-CD in human plasma and CSF.
AB  - 2-Hydroxypropyl-beta-cyclodextrin (HP-beta-CD), a widely used excipient for drug
      formulation, has emerged as an investigational new drug for the treatment of
      Niemann-Pick type C1 (NPC1) disease, a neurodegenerative cholesterol storage
      disorder. Development of a sensitive quantitative LC-MS/MS assay to monitor the
      pharmacokinetics (PKs) of HP-beta-CD required for clinical trials has been
      challenging owing to the dispersity of the HP-beta-CD. To support a phase 1
      clinical trial for ICV delivery of HP-beta-CD in NPC1 patients, novel methods for
      quantification of HP-beta-CD in human plasma and cerebrospinal fluid (CSF) using
      LC-MS/MS were developed and validated: a 2D-LC-in-source fragmentation-MS/MS (2D
      LC-IF-MS/MS) assay and a reversed phase ultra performance LC-MS/MS (RP-UPLC
      MS/MS) assay. In both assays, protein precipitation and "dilute and shoot"
      procedures were used to process plasma and CSF, respectively. The assays were
      fully validated and in close agreement, and allowed determination of PK
      parameters for HP-beta-CD. The LC-MS/MS methods are ~100-fold more sensitive than
      the current HPLC assay, and were successfully employed to analyze HP-beta-CD in
      human plasma and CSF samples to support the phase 1 clinical trial of HP-beta-CD
      in NPC1 patients.

PMID- 24868099
TI  - Phase II study of Afatinib as third-line treatment for patients in Korea with
      stage IIIB/IV non-small cell lung cancer harboring wild-type EGFR.
AB  - BACKGROUND: This phase II single-arm trial evaluated afatinib, an irreversible
      inhibitor of the ErbB receptor family as third-line treatment of Korean patients
      with advanced non-small cell lung cancer (NSCLC) and tumors with wild-type EGFR.
      Currently, no standard therapy exists for these patients. METHODS: Eligible
      patients had stage IIIB/IV wild-type EGFR lung adenocarcinoma and had failed to
      benefit from two previous lines of chemotherapy but had not received anti-EGFR
      treatment. Patients received oral afatinib at 40 mg per day until disease
      progression or occurrence of intolerable adverse events (AEs). The primary
      endpoint was confirmed objective tumor response (OR) rate (confirmed complete
      response [CR] or partial response [PR]). Secondary endpoints included disease
      control rate (DCR; OR or stable disease for >=6 weeks), progression-free survival
      (PFS), and safety. RESULTS: Forty-two patients received afatinib treatment, and
      38 of those were included in efficacy analyses. No confirmed CRs or PRs were
      reported. DCR was 24% (9 of 38 patients), with a median disease control duration
      of 19.3 weeks. Median PFS was 4.1 weeks (95% confidence interval: 3.9-8.0).
      Frequently reported AEs (mainly grades 1 and 2) were rash/acne (88%), diarrhea
      (62%), and stomatitis (57%). CONCLUSION: Heavily pretreated patients with wild
      type EGFR NSCLC treated with afatinib monotherapy did not experience an objective
      response and only 24% had disease stabilization lasting more than 6 weeks. AEs
      were manageable and consistent with the expected safety profile.

PMID- 24868101
TI  - Noncoding RNAs: 'our turn' to join the p53 network.

PMID- 24868098
TI  - U.S. Food and Drug Administration approval summary: Erlotinib for the first-line
      treatment of metastatic non-small cell lung cancer with epidermal growth factor
      receptor exon 19 deletions or exon 21 (L858R) substitution mutations.
AB  - On May 14, 2013, the U.S. Food and Drug Administration approved erlotinib
      (Tarceva, Astellas Pharma Inc., Northbrook, IL, http://www.us.astellas.com/) for
      the first-line treatment of patients with metastatic non-small cell lung cancer
      (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19
      deletions or exon 21 (L858R) substitution mutations. This indication for
      erlotinib was approved concurrently with the cobas EGFR Mutation Test (Roche
      Molecular Systems, Inc., Basel, Switzerland, http://www.molecular.roche.com), a
      companion diagnostic test for patient selection. The approval was based on
      clinically important improvements in progression-free survival (PFS) and
      objective response rate (ORR) and an acceptable toxicity profile demonstrated in
      a multicenter, open label trial enrolling 174 patients with metastatic NSCLC
      whose tumors had EGFR mutations as determined by a laboratory-developed test.
      Patients were randomized (1:1) to receive erlotinib (150 mg/day) or platinum
      based doublet chemotherapy. The primary endpoint was investigator-assessed PFS.
      Secondary endpoints included overall survival (OS) and ORR. Superior PFS (hazard
      ratio [HR] 0.34; 95% confidence interval [CI]: 0.23, 0.49; p < .001) and ORR (65%
      vs. 16%) were observed in the erlotinib arm. Median PFS was 10.4 months and 5.2
      months in the erlotinib and chemotherapy arms, respectively. There was no
      difference in OS (HR 0.93; 95% CI: 0.64, 1.35) with median OS of 22.9 months and
      19.5 months in the erlotinib and chemotherapy arms, respectively. The most
      frequent (>=30%) adverse reactions in the erlotinib-treated patients were rash,
      diarrhea, asthenia, cough, dyspnea, and decreased appetite. The most frequent
      (>=5%) grade 3 and 4 adverse reactions were rash and diarrhea. 

PMID- 24868100
TI  - Patterns of storage, use, and disposal of opioids among cancer outpatients.
AB  - PURPOSE: Improper storage, use, and disposal of prescribed opioids can lead to
      diversion or accidental poisoning. Our objective was to determine the patterns of
      storage, utilization, and disposal of opioids among cancer outpatients. PATIENTS
      AND METHODS: We surveyed 300 adult cancer outpatients receiving opioids in our
      supportive care center and collected information regarding opioid use, storage,
      and disposal, along with scores on the CAGE (cut down, annoyed, guilty, eye
      opener) alcoholism screening questionnaire. Unsafe use was defined as sharing or
      losing opioids; unsafe storage was defined as storing opioids in plain sight.
      RESULTS: The median age was 57 years. CAGE was positive in 58 of 300 patients
      (19%), and 26 (9%) had a history of illicit drug use. Fifty-six (19%) stored
      opioids in plain sight, 208 (69%) kept opioids hidden but unlocked, and only 28
      (9%) locked their opioids. CAGE-positive patients (p = .007) and those with a
      history of illicit drug use (p = .0002) or smoking (p = .03) were more likely to
      lock their opioids. Seventy-eight (26%) reported unsafe use by sharing (9%) or
      losing (17%) their opioids. Patients who were never married or single (odds
      ratio: 2.92; 95% confidence interval: 1.48-5.77; p = .006), were CAGE positive
      (40% vs. 21%; p = .003), or had a history of illicit drug use (42% vs. 23%; p =
      .031) were more likely to use opioids unsafely. Overall, 223 of 300 patients
      (74%) were unaware of proper opioid disposal methods, and 138 (46%) had unused
      opioids at home. CONCLUSION: A large proportion of cancer patients improperly and
      unsafely use, store, and dispose of opioids, highlighting the need for
      establishment of easily accessed patient education and drug take-back programs.

PMID- 24868103
TI  - Molecular evolution of GPCRs: What we know and what the future holds.

PMID- 24868102
TI  - microRNAs and Alu elements in the p53-Mdm2-Mdm4 regulatory network.
AB  - p53 is a transcription factor that governs numerous stress response pathways
      within the cell. Maintaining the right levels of p53 is crucial for cell survival
      and proper cellular homeostasis. The tight regulation of p53 involves many
      cellular components, most notably its major negative regulators Mdm2 and Mdm4,
      which maintain p53 protein amount and activity in tight check. microRNAs (miRNAs)
      are small non-coding RNAs that target specific mRNAs to translational arrest and
      degradation. miRNAs are also key components of the normal p53 pathway, joining
      forces with Mdm2 and Mdm4 to maintain proper p53 activity. Here we review the
      current knowledge of miRNAs targeting Mdm2 and Mdm4, and their importance in
      different tissues and in pathological states such as cancer. In addition, we
      address the role of Alu sequences-highly abundant retroelements spread throughout
      the human genome, and their impact on gene regulation via the miRNA machinery.
      Alus occupy a significant portion of genes' 3'UTR, and as such they have the
      potential to impact mRNA regulation. Since Alus are primate-specific, they
      introduce a new regulatory layer into primate genomes. Alus can influence and
      alter gene regulation, creating primate-specific cancer-preventive regulatory
      mechanisms to sustain the transition to longer life span in primates. We review
      the possible influence of Alu sequences on miRNA functionality in general and
      specifically within the p53 network. 

PMID- 24868104
TI  - Molecular evolution of GPCRs: Secretin/secretin receptors.
AB  - In mammals, secretin is a 27-amino acid peptide that was first studied in 1902 by
      Bayliss and Starling from the extracts of the jejunal mucosa for its ability to
      stimulate pancreatic secretion. To date, secretin has only been identified in
      tetrapods, with the earliest diverged secretin found in frogs. Despite being the
      first hormone discovered, secretin's evolutionary origin remains enigmatic, it
      shows moderate sequence identity in nonmammalian tetrapods but is highly
      conserved in mammals. Current hypotheses suggest that although secretin has
      already emerged before the divergence of osteichthyans, it was lost in fish and
      retained only in land vertebrates. Nevertheless, the cognate receptor of secretin
      has been identified in both actinopterygian fish (zebrafish) and sarcopterygian
      fish (lungfish). However, the zebrafish secretin receptor was shown to be
      nonbioactive. Based on the present information that the earliest diverged
      bioactive secretin receptor was found in lungfish, and its ability to interact
      with both vasoactive intestinal peptide and pituitary adenylate cyclase
      activating polypeptide potently suggested that secretin receptor was descended
      from a VPAC-like receptor gene before the Actinopterygii-Sarcopterygii split in
      the vertebrate lineage. Hence, secretin and secretin receptor have gone through
      independent evolutionary trajectories despite their concurrent emergence post-2R.
      A functional secretin-secretin receptor axis has probably emerged in the
      amphibians. Although the pleiotropic actions of secretin are well documented in
      the literature, only limited information of its physiological functions in
      nonmammalian tetrapods have been reported. To decipher the structural and
      functional divergence of secretin and secretin receptor, functional
      characterization of the ligand-receptor pair in nonmammals would be the next
      perspective for investigation. 

PMID- 24868105
TI  - Molecular evolution of GPCRs: Melanocortin/melanocortin receptors.
AB  - The melanocortin receptors (MCRs) are a family of G protein-coupled receptors
      that are activated by melanocortin ligands derived from the proprotein,
      proopiomelanocortin (POMC). During the radiation of the gnathostomes, the five
      receptors have become functionally segregated (i.e. melanocortin 1 receptor
      (MC1R), pigmentation regulation; MC2R, glucocorticoid synthesis; MC3R and MC4R,
      energy homeostasis; and MC5R, exocrine gland physiology). A focus of this review
      is the role that ligand selectivity plays in the hypothalamus/pituitary/adrenal
      interrenal (HPA-I) axis of teleosts and tetrapods as a result of the exclusive
      ligand selectivity of MC2R for the ligand ACTH. A second focal point of this
      review is the roles that the accessory proteins melanocortin 2 receptor accessory
      protein 1 (MRAP1) and MRAP2 are playing in, respectively, the HPA-I axis (MC2R)
      and the regulation of energy homeostasis by neurons in the hypothalamus (MC4R) of
      teleosts and tetrapods. In addition, observations are presented on trends in the
      ligand selectivity parameters of cartilaginous fish, teleost, and tetrapod MC1R,
      MC3R, MC4R, and MC5R paralogs, and the modeling of the HFRW motif of ACTH(1-24)
      when compared with alpha-MSH. The radiation of the MCRs during the evolution of
      the gnathostomes provides examples of how the physiology of endocrine and
      neuronal circuits can be shaped by ligand selectivity, the intersession of
      reverse agonists (agouti-related peptides (AGRPs)), and interactions with
      accessory proteins (MRAPs). 

PMID- 24868106
TI  - Use of Fc-Engineered Antibodies as Clearing Agents to Increase Contrast During
      PET.
AB  - Despite promise for the use of antibodies as molecular imaging agents in PET,
      their long in vivo half-lives result in poor contrast and radiation damage to
      normal tissue. This study describes an approach to overcome these limitations.
      METHODS: Mice bearing human epidermal growth factor receptor type 2 (HER2)
      overexpressing tumors were injected with radiolabeled ((124)I, (125)I) HER2
      specific antibody (pertuzumab). Pertuzumab injection was followed 8 h later by
      the delivery of an engineered, antibody-based inhibitor of the receptor, FcRn.
      Biodistribution analyses and PET were performed at 24 and 48 h after pertuzumab
      injection. RESULTS: The delivery of the engineered, antibody-based FcRn inhibitor
      (or Abdeg, for antibody that enhances IgG degradation) results in improved tumor
      to-blood ratios, reduced systemic exposure to radiolabel, and increased contrast
      during PET. CONCLUSION: Abdegs have considerable potential as agents to
      stringently regulate antibody dynamics in vivo, resulting in increased contrast
      during molecular imaging with PET.

PMID- 24868107
TI  - Quantification of 18F-Fluoride Kinetics: Evaluation of Simplified Methods.
AB  - (18)F-fluoride PET is a promising noninvasive method for measuring bone
      metabolism and bone blood flow. The purpose of this study was to assess the
      performance of various clinically useful simplified methods by comparing them
      with full kinetic analysis. In addition, the validity of deriving bone blood flow
      from K1 of (18)F-fluoride was investigated using (15)O-H2O as a reference.
      METHODS: Twenty-two adults (mean age +/- SD, 44.8 +/- 25.2 y), including 16
      patients scheduled for bone surgery and 6 healthy volunteers, were studied. All
      patients underwent dynamic (15)O-H2O and (18)F-fluoride scans before surgery. Ten
      of these patients had serial PET measurements before and at 2 time points after
      local bone surgery. During all PET scans, arterial blood was monitored
      continuously. (18)F-fluoride data were analyzed using nonlinear regression (NLR)
      and several simplified methods (Patlak and standardized uptake value [SUV]). SUV
      was evaluated for different time intervals after injection and after normalizing
      to body weight, lean body mass, and body surface area, and simplified
      measurements were compared with NLR results. In addition, changes in SUV and
      Patlak-derived fluoride influx rate (Ki) after surgery were compared with
      corresponding changes in NLR-derived Ki. Finally, (18)F-fluoride K1 was compared
      with bone blood flow derived from (15)O-H2O data, using the standard single
      tissue-compartment model. RESULTS: K1 of (18)F-fluoride correlated with measured
      blood flow, but the correlation coefficient was relatively low (r = 0.35, P <
      0.001). NLR resulted in a mean Ki of 0.0160 +/- 0.0122, whereas Patlak analysis,
      for the interval 10-60 min after injection, resulted in an almost-identical mean
      Ki of 0.0161 +/- 0.0117. The Patlak-derived Ki, for 10-60 min after injection,
      showed a high correlation with the NLR-derived Ki (r = 0.976). The highest
      correlation between Ki and lean body mass-normalized SUV was found for the
      interval 50-60 min (r = 0.958). Finally, changes in SUV correlated significantly
      with those in Ki (r = 0.97). CONCLUSION: The present data support the use of both
      Patlak and SUV for assessing fluoride kinetics in humans. However, (18)F-fluoride
      PET has only limited accuracy in monitoring bone blood flow.

PMID- 24868108
TI  - Effect of Platinum-Based Chemoradiotherapy on Cellular Proliferation in Bone
      Marrow and Spleen, Estimated by (18)F-FLT PET/CT in Patients with Locally
      Advanced Non-Small Cell Lung Cancer.
AB  - Historically, it has been difficult to monitor the acute impact of anticancer
      therapies on hematopoietic organs on a whole-body scale. Deeper understanding of
      the effect of treatments on bone marrow would be of great potential value in the
      rational design of intensive treatment regimens. 3'-deoxy-3'-(18)F
      fluorothymidine ((18)F-FLT) is a functional radiotracer used to study cellular
      proliferation. It is trapped in cells in proportion to thymidine-kinase 1 enzyme
      expression, which is upregulated during DNA synthesis. This study investigates
      the potential of (18)F-FLT to monitor acute effects of chemotherapy on cellular
      proliferation and its recovery in bone marrow, spleen, and liver during treatment
      with 2 different chemotherapy regimens. METHODS: Sixty patients with non-small
      cell lung cancer underwent concurrent radical chemoradiotherapy to 60 Gy in 6 wk
      with either cisplatin/etoposide (C/E, n = 28) weeks 1 and 5 or weekly
      carboplatin/paclitaxel (C/P, n = 32) regimens. (18)F-FLT and (18)F-FDG PET with
      CT were performed at baseline, week 2 (day 9 for (18)F-FLT and day 10 for (18)F
      FDG PET), and week 4 (day 23 for (18)F-FLT and day 24 for (18)F-FDG PET). Visual
      and semiquantitative standardized uptake value (SUV) measurements were performed
      in bone marrow outside the radiotherapy field, liver, spleen, and small bowel.
      These were correlated to blood counts and smears in a subset of patients.
      RESULTS: The C/E group exhibited a drop in bone marrow (18)F-FLT uptake at week 2
      (median SUVmax [maximum SUV] decrease to 31%, 8.7-6.0, P < 0.001), with recovery
      at week 4, reflecting the absence of chemotherapy between these times. By
      contrast, the weekly C/P group showed gradually declining bone marrow uptake (P >
      0.05). Spleen uptake in both cohorts decreased at week 2, with intense rebound
      activity at week 4 (SUVmax week 4 at 58% above baseline: 2.4-3.8, for C/E,
      respectively, 30% for C/P: 2.7-3.5, P < 0.001). Liver uptake changed little.
      (18)F-FLT changes preceded neutrophil count reductions. (18)F-FDG uptake in
      marrow liver and spleen changed much less than (18)F-FLT. CONCLUSION: (18)F-FLT
      imaging may be used to quantify impairment and recovery of bone marrow by
      specific chemotherapy regimens and may also enable imaging of organ-specific
      processes such as spleen activation. (18)F-FLT is superior to (18)F-FDG for this
      purpose. This technology may support novel treatment planning and monitoring
      approaches in oncology patients.

PMID- 24868109
TI  - Clinical implication of PET/MR imaging in preoperative esophageal cancer staging:
      comparison with PET/CT, endoscopic ultrasonography, and CT.
AB  - This was a study to compare the diagnostic efficacies of endoscopic
      ultrasonography (EUS), CT, PET/MR imaging, and PET/CT for the preoperative local
      and regional staging of esophageal cancer, with postoperative pathologic stage
      used as the reference standard. METHODS: During 1 y, 19 patients with resectable
      esophageal cancer were enrolled and underwent preoperative EUS, CT, PET/CT, and
      PET/MR imaging. A chest radiologist and nuclear medicine physician
      retrospectively reviewed the images and assigned tumor and lymph node stages
      according to the seventh version of the TNM system and the American Joint
      Committee on Cancer staging system. Four patients who were treated nonsurgically
      were excluded from data analysis. The efficacies of EUS, CT, PET/CT, and PET/MR
      imaging were compared. RESULTS: Primary tumors were correctly staged in 13
      (86.7%), 10 (66.7%), and 5 (33.3%) patients at EUS, PET/MR imaging, and CT,
      respectively (P value ranging from 0.021 to 0.375). The accuracy of determining
      T1 lesions was 86.7%, 80.0%, and 46.7% for EUS, PET/MR imaging, and CT,
      respectively. For distinguishing T3 lesions, the accuracy was 93.3% for EUS and
      86.7% for both PET/MR imaging and CT. For lymph node staging, the accuracy was
      83.3%, 75.0%, 66.7%, and 50.0% for PET/MR imaging, EUS, PET/CT, and CT,
      respectively. In addition, area-under-the-curve values were 0.800, 0.700, 0.629,
      and 0.543 for PET/MR imaging, EUS, PET/CT, and CT, respectively. CONCLUSION:
      PET/MR imaging demonstrated acceptable accuracy for T staging compared with EUS
      and, although not statistically significant, even higher accuracy than EUS and
      PET/CT for prediction of N staging. With adjustments in protocols, PET/MR imaging
      may provide an important role in preoperative esophageal cancer staging in the
      future.

PMID- 24868111
TI  - Metabolic profiling in diabetes.
AB  - Metabolic profiling, or metabolomics, has developed into a mature science in
      recent years. It has major applications in the study of metabolic disorders. This
      review addresses issues relevant to the choice of the metabolomics platform,
      study design and data analysis in diabetes research, and presents recent advances
      using metabolomics in the identification of markers for altered metabolic
      pathways, biomarker discovery, challenge studies, metabolic markers of drug
      efficacy and off-target effects. The role of genetic variance and intermediate
      metabolic phenotypes and its relevance to diabetes research is also addressed. 

PMID- 24868110
TI  - Inactivation of the adrenergic receptor beta2 disrupts glucose homeostasis in
      mice.
AB  - Three types of beta adrenergic receptors (ARbeta1-3) mediate the sympathetic
      activation of brown adipose tissue (BAT), the key thermogenic site for mice which
      is also present in adult humans. In this study, we evaluated adaptive
      thermogenesis and metabolic profile of a mouse with Arbeta2 knockout (ARbeta2KO).
      At room temperature, ARbeta2KO mice have normal core temperature and, upon acute
      cold exposure (4  degrees C for 4 h), ARbeta2KO mice accelerate energy
      expenditure normally and attempt to maintain body temperature. ARbeta2KO mice
      also exhibited normal interscapular BAT thermal profiles during a 30-min infusion
      of norepinephrine or dobutamine, possibly due to marked elevation of
      interscapular BAT (iBAT) and of Arbeta1, and Arbeta3 mRNA levels. In addition,
      ARbeta2KO mice exhibit similar body weight, adiposity, fasting plasma glucose,
      cholesterol, and triglycerides when compared with WT controls, but exhibit marked
      fasting hyperinsulinemia and elevation in hepatic Pepck (Pck1) mRNA levels. The
      animals were fed a high-fat diet (40% fat) for 6 weeks, ARbeta2KO mice doubled
      their caloric intake, accelerated energy expenditure, and induced Ucp1 expression
      in a manner similar to WT controls, exhibiting a similar body weight gain and
      increase in the size of white adipocytes to the WT controls. However, ARbeta2KO
      mice maintain fasting hyperglycemia as compared with WT controls despite very
      elevated insulin levels, but similar degrees of liver steatosis and
      hyperlipidemia. In conclusion, inactivation of the ARbeta2KO pathway preserves
      cold- and diet-induced adaptive thermogenesis but disrupts glucose homeostasis
      possibly by accelerating hepatic glucose production and insulin secretion.
      Feeding on a high-fat diet worsens the metabolic imbalance, with significant
      fasting hyperglycemia but similar liver structure and lipid profile to the WT
      controls. 

PMID- 24868112
TI  - FT-IR analysis of urinary stones: a helpful tool for clinician comparison with
      the chemical spot test.
AB  - BACKGROUND: Kidney stones are a common illness with multifactorial
      etiopathogenesis. The determination of crystalline and molecular composition and
      the quantification of all stone components are important to establish the
      etiology of stones disease but it is often laborious to obtain using the chemical
      method. The aim of this paper is to compare chemical spot test with FT-IR
      spectroscopy, for a possible introduction in our laboratory. METHODS: We analyzed
      48 calculi using Urinary Calculi Analysis kit in accordance with the
      manufacturer's instructions. The same samples were analyzed by FT-IR using the
      Perkin Elmer Spectrum One FT-IR Spectrometer. All FT-IR spectra of kidney stones
      were then computer matched against a library of spectra to generate a report on
      the various components. RESULTS: On the basis of FT-IR analysis, the 48 calculi
      were divided into three groups: pure stone, mixed stone, and pure stone with
      substances in trace. Results of each group were compared with those obtained with
      chemical spot test. A general disagreement between methods was observed.
      CONCLUSIONS: According to our data, the introduction of the FT-IR technique in
      clinical chemistry laboratory may be more responsive to clinician expectations.

PMID- 24868113
TI  - Haptoglobin 2-2 genotype is associated with TNF- alpha and IL-6 levels in
      subjects with obesity.
AB  - OBJECTIVE: To evaluate the association between Haptoglobin (HP) gene
      polymorphisms with inflammatory status in obese subjects. MATERIALS AND METHODS:
      A cross-sectional study was carried out. A total of 276 apparently healthy men
      and nonpregnant obese women were enrolled and allocated according to the HP
      genotype into the HP (1)/HP (1), HP (2)/HP (1), and HP (2)/HP (2) groups.
      Distribution of HP genotypes was 49, 87, and 140 for the HP (1)/HP (1), HP (2)/HP
      (1), and HP (2)/HP (2), respectively. The HP genotype was determined using the
      polymerase chain reaction method. A multiple linear regression analysis adjusted
      by age, sex, waist circumference, and total body fat was used to determine the
      association between HP genotypes with TNF- alpha , IL-6, and high-sensitivity C
      reactive protein (hsCRP) levels. RESULTS: A multiple linear regression analysis
      adjusted by sex, waist circumference, and total body fat was performed showing a
      significant association between the HP (2)/HP (2) genotype and TNF- alpha ( beta
      = 0.180; 95% CI 14.41-159.64, P = 0.01) and IL-6 ( beta = 0.188; 95% CI 1.53
      12.72, P = 0.01) levels, but not with hsCRP ( beta = -0.008; 95% CI -1.64-1.47, P
      = 0.914) levels, whereas the HP (2)/HP (1) genotype showed no association
      compared with the HP (1)/HP (1) genotype (control group). CONCLUSION: Results of
      our study show that the HP (2)/HP (2) genotype is associated with elevated TNF-
      alpha and IL-6, but not with hsCRP, levels in obese subjects.

PMID- 24868114
TI  - Does aerobic exercise training promote changes in structural and biomechanical
      properties of the tendons in experimental animals? A systematic review.
AB  - To develop a systematic review to evaluate, through the best scientific evidence
      available, the effectiveness of aerobic exercise in improving the biomechanical
      characteristics of tendons in experimental animals. Two independent assessors
      conducted a systematic search in the databases Medline/PUBMED and Lilacs/BIREME,
      using the following descriptors of Mesh in animal models. The ultimate load of
      traction and the elastic modulus tendon were used as primary outcomes and
      transverse section area, ultimate stress and tendon strain as secondary outcomes.
      The assessment of risk of bias in the studies was carried out using the following
      methodological components: light/dark cycle, temperature, nutrition, housing,
      research undertaken in conjunction with an ethics committee, randomization,
      adaptation of the animals to the training and preparation for the mechanical
      test. Eight studies, comprising 384 animals, were selected; it was not possible
      to combine them into one meta-analysis due to the heterogeneity of the samples.
      There was a trend to increasing ultimate load without changes in the other
      outcomes studied. Only one study met more than 80% of the quality criteria.
      Physical training performed in a structured way with imposition of overloads
      seems to be able to promote changes in tendon structure of experimental models by
      increasing the ultimate load supported. However, the results of the influence of
      exercise on the elastic modulus parameters, strain, transverse section area and
      ultimate stress, remain controversial and inconclusive. Such a conclusion must be
      evaluated with reservation as there was low methodological control in the studies
      included in this review. 

PMID- 24868116
TI  - Training-induced changes in drag-flick technique in female field hockey players.
AB  - The penalty corner is one of the most important goal plays in field hockey. The
      drag-flick is used less by women than men in a penalty corner. The aim of this
      study was to describe training-induced changes in the drag-flick technique in
      female field hockey players. Four female players participated in the study. The
      VICON optoelectronic system (Oxford Metrics, Oxford, UK) measured the kinematic
      parameters of the drag-flick with six cameras sampling at 250 Hz, prior to and
      after training. Fifteen shots were captured for each subject. A Wilcoxon test
      assessed the differences between pre-training and post-training parameters. Two
      players received specific training twice a week for 8 weeks; the other two
      players did not train. The proposed drills improved the position of the stick at
      the beginning of the shot (p < 0.05), the total distance of the shot (p < 0.05)
      and the rotation radius at ball release (p < 0.01). It was noted that all players
      had lost speed of the previous run. Further studies should include a larger
      sample, in order to provide more information on field hockey performance. 

PMID- 24868115
TI  - Effect of exercise on the level of immunoglobulin a in saliva.
AB  - The aim of this paper is to describe the structure, production and function of
      secretory immunoglobulin A (sIgA) as well as changes of its concentration caused
      by exercise of various intensity and duration. Immunoglobulin A is the main class
      of antibodies present in the body secreted fluids such as saliva, tears or mucus
      from the intestines. It is generally recognized that IgA, due to its dominance in
      the immune system of mucous membranes, is the first line of defence against
      harmful environmental factors. The secretion and composition of saliva depends on
      the activity of the sympathetic and parasympathetic nervous systems. Physical
      activity, stimulating the autonomous nervous system, may reduce the amount of
      saliva and/or inhibit its secretion. The relationship between physical activity
      and the suppression of the immune system is not fully understood, but it is known
      that moderate intensity exercise can improve immune defences, while extreme
      effort can reduce them by creating an increased risk of upper respiratory tract
      inflammation (URTI). In athletes, the lowest risk of upper tract infection was
      connected with the case of moderate intensity exercise. It is now believed that
      the relationship between exercise volume and the risk of URTI has the shape of
      the letter "J". This means that both too little and too much physical activity
      may increase the risk of upper respiratory tract infection. Training optimization
      and correct balance between exercise and rest periods may reduce the risk of
      adverse changes in the immune system and decrease the frequency of URTI. 

PMID- 24868118
TI  - Physical fitness and nutritional status of polish ground force unit recruits.
AB  - The purpose of the work was to conduct an examination of the physical fitness and
      nutritional status of recruits (221 men beginning military service in the
      infantry unit). Soldiers' physical efficiency was estimated using 4 tests:
      standing long jump, pull-ups on bar, 30-second sit-ups and 1000-metre run. The
      nutritional status assessment was done based on anthropometric measurements
      including measurements of body height, body mass and selected skin fold
      thickness. The study group of soldiers were the best at sit-ups (46.33 points).
      They got over 40 points for the 1000-metre run (43.68 points) and for pull-ups on
      bar (41.69 points). They obtained the lowest scores for standing long jumps
      (30.77 points). About 14% of recruits were overweight and 4.1% underweight.
      Recruits enrolling in the infantry unit present a low physical fitness level.
      Overweight and obesity occurrence, and particularly underweight, in recruits
      testify to improper nutrition before beginning military service. 

PMID- 24868117
TI  - Different recovery methods and muscle performance after exhausting exercise:
      comparison of the effects of electrical muscle stimulation and massage.
AB  - In this study we assessed the influence of the three different recovery
      interventions massage (MSG), electrical muscle stimulation (EMS), and passive
      rest (PR) on lactate disappearance and muscle recovery after exhausting exercise
      bouts. Twelve healthy male sport students participated in the study. They
      attended the laboratory on five test days. After measurement of [Formula: see
      text]O2max and a baseline Wingate test (WGb), the three recovery interventions
      were tested in random counterbalanced order. High intensity exercise, which
      consisted of six exhausting exercise bouts (interspersed with active recovery),
      was followed by MSG, EMS or PR application (24 minutes); then the final Wingate
      test (WGf) was performed. Lactate, heart rate, peak and mean power, rating of
      perceived exertion (RPE), and total quality of recovery (TQR) were recorded. In
      WGf mean power was significantly higher than in WGb for all three recovery
      modalities (MSG 6.29%, EMS 5.33%, PR 4.84% increase, p < 0.05), but no
      significant differences in mean and peak power were observed between the three
      recovery modes (p > 0.05). The heart rate response and the changes in blood
      lactate concentration were identical in all three interventions during the entire
      protocol (p = 0.817, p = 0.493, respectively). RPE and TQR scores were also not
      different among the three interventions (p > 0.05). These results provide further
      evidence that MSG and EMS are not more effective than PR in the process of
      recovery from high intensity exercise. 

PMID- 24868119
TI  - Validity of the standing spike test as a monitoring protocol for female
      volleyball players.
AB  - THE PURPOSE OF THIS PAPER WAS: a) to provide reference values for the standing
      spike test for female volleyball players and b) to study whether the standing
      spike test is valid for assessing the theoretical differences between female
      volleyball players. The sample included 83 players from the first nine teams of
      the Spanish women's first volleyball division (52 Spanish players and 31 from
      other nationalities). The variables studied were the ball speed of the standing
      spike test, the age of the players, the player's role (outside hitter, opposite,
      middle-blocker, libero, or setter), height, and nationality of the players
      (Spanish or foreign). The results demonstrate the ranges for the standing spike
      among female performance volleyball players (70-82 km . h(-1)). The differences
      regarding nationality, player role, height, and age seem to indicate that the
      test is a valid instrument for monitoring the performance of female volleyball
      players.

PMID- 24868120
TI  - Mapping remote subcortical ramifications of injury after ischemic strokes.
AB  - BACKGROUND: The extent of brain damage in chronic stroke patients is
      traditionally defined as the necrotic tissue observed on magnetic resonance image
      (MRI). However, patients often exhibit symptoms suggesting that functional
      impairment may affect areas beyond the cortical necrotic lesion, for example,
      when cortical symptoms ensue after subcortical damage. This observation suggests
      that disconnection or diaschisis can lead to remote cortical dysfunction that can
      be functionally equivalent to direct cortical lesions. Objective. To directly
      measure subcortical disconnection after stroke. METHODS: We describe a principled
      approach utilizing the whole brain connectome reconstructed from diffusion MRI to
      evaluate the reduction of apparent white matter fiber density in the hemisphere
      affected by the stroke compared with the spared hemisphere. RESULTS: In eight
      chronic stroke patients, we observed subcortical disconnection extending beyond
      the location of tissue necrosis and affecting major white matter pathways
      underlying the necrotic area. CONCLUSIONS: We suggest that it is possible to
      detect and quantify previously unappreciated areas of subcortical and cortical
      disconnection. Specifically, this method can be used to evaluate the relationship
      between lesion location and symptoms, with emphasis on a connectivity-based
      approach.

PMID- 24868121
TI  - Executive and language control in the multilingual brain.
AB  - Neuroimaging studies suggest that the neural network involved in language control
      may not be specific to bi-/multilingualism but is part of a domain-general
      executive control system. We report a trilingual case of a Cantonese (L1),
      English (L2), and Mandarin (L3) speaker, Dr. T, who sustained a brain injury at
      the age of 77 causing lesions in the left frontal lobe and in the left temporo
      parietal areas resulting in fluent aphasia. Dr. T's executive functions were
      impaired according to a modified version of the Stroop color-word test and the
      Wisconsin Card Sorting Test performance was characterized by frequent
      perseveration errors. Dr. T demonstrated pathological language switching and
      mixing across her three languages. Code switching in Cantonese was more prominent
      in discourse production than confrontation naming. Our case suggests that
      voluntary control of spoken word production in trilingual speakers shares neural
      substrata in the frontobasal ganglia system with domain-general executive control
      mechanisms. One prediction is that lesions to such a system would give rise to
      both pathological switching and impairments of executive functions in trilingual
      speakers. 

PMID- 24868123
TI  - A family-centered cesarean birth story.
AB  - This is the family-centered cesarean birth story of my twin grandchildren.
      Because of good prenatal education; a well-chosen, dedicated care provider; and
      parents with focus, I am able to share a beautiful birth story. I hope relating
      this story encourages other childbirth educators to present various options for
      cesarean in their classes, thereby educating the public about this beautiful
      opportunity if a cesarean birth is necessary. 

PMID- 24868124
TI  - Expert workshop assesses the significance of birth location on maternal and
      infant outcomes.
AB  - On March 6-7, 2013, some of the greatest minds in research and the provision of
      maternity care came together for a workshop on "Research Issues in the Assessment
      of Birth Settings," hosted by the prestigious Institute of Medicine (IOM) and
      sponsored by the W.K. Kellogg Foundation. 

PMID- 24868125
TI  - Women's Perceptions Using the CenteringPregnancy Model of Group Prenatal Care.
AB  - A qualitative nonexperimental thematic analysis was conducted at a hospital-based
      midwifery practice to explore the views of participants in group prenatal care
      and its impact on pregnancy, birth, and postnatal care. Ten women and three
      support people, recruited through purposive sampling, shared their feedback on
      the program. The findings conveyed three broad themes: program experience,
      midwife relationship, and support. Women enjoyed the opportunity for in-depth
      learning, and peer-group support led to normalizing of pregnancy concerns. Having
      support people as participants also helped during pregnancy, birth, and child
      care. The findings showed the enhanced opportunity for education, learning, and
      interpersonal support provided by CenteringPregnancy to expectant mothers had a
      positive impact on their pregnancy experiences. 

PMID- 24868122
TI  - Preclinical polymodal hallucinations for 13 years before dementia with Lewy
      bodies.
AB  - OBJECTIVE: We describe a case of dementia with Lewy bodies (DLB) that presented
      long-lasting preclinical complex polymodal hallucinations. BACKGROUND: Few
      studies have deeply investigated the characteristics of hallucinations in DLB,
      especially in the preclinical phase. Moreover, the clinical phenotype of mild
      cognitive impairment-(MCI-) DLB is poorly understood. METHODS: The patient was
      followed for 4 years and a selective phenomenological and cognitive study was
      performed at the predementia stage. RESULTS: The phenomenological study showed
      the presence of hypnagogic and hypnopompic hallucinations that allowed us to make
      a differential diagnosis between DLB and Charles Bonnet syndrome (CBS). The
      neuropsychological evaluation showed a multiple domain without amnesia MCI
      subtype with prefrontal dysexecutive, visuoperceptual, and visuospatial
      impairments and simultanagnosia, which has not previously been reported in MCI
      DLB. CONCLUSIONS: This study extends the prognostic value of hallucinations for
      DLB to the preclinical phases. It supports and refines the MCI-DLB concept and
      identifies simultanagnosia as a possible early cognitive marker. Finally, it
      confirms an association between hallucinations and visuoperceptual impairments at
      an intermediate stage of the disease course and strongly supports the hypothesis
      that hallucinations in the earliest stages of DLB may reflect a narcolepsy-like
      REM-sleep disorder.

PMID- 24868126
TI  - Supporting maternal transition: continuity, coaching, and control.
AB  - The transition from maternity services to community child health services on
      discharge from hospital occurs at a potentially vulnerable time for women in
      their transition through the childbearing/early parenting continuum. Their
      experiences contribute to their developing maternal efficacy and parenting skill.
      The ideal attributes of services that aim to support women and their families
      during this time include continuity of care, service integration, and birth in
      accessible, community-based contexts. The purpose of this study was to
      investigate aspects of maternal experience of mothers attending with their
      infants a publicly funded drop-in postnatal health-care service, as well as their
      reasons for attending and their perceptions of its usefulness to them as a
      mechanism of continuity and a source of support. 

PMID- 24868129
TI  - Choice? Factors That Influence Women's Decision Making for Childbirth.
AB  - This article reports the findings from a mixed-methods study on factors that
      influence women's decisions about birth, with the view that women's decision
      making about birth can affect the use of cesarean surgery. Data was collected
      from focus groups and structured postpartum interviews and was analyzed using the
      Consensual Qualitative Research method. The findings relate specifically to the
      factors reported as influential in making decisions about birth including how the
      women categorized, prioritized, and/or favored certain types of knowledge about
      modes of birth. Four major information categories were identified but only
      stories about birth and/or attending a birth appeared to have a lasting effect on
      birth choices. These findings have implications for prenatal and perinatal
      education and nursing practice. 

PMID- 24868127
TI  - Fetal monitoring: creating a culture of safety with informed choice.
AB  - The dominant culture in labor and birth is the medical model, not the midwifery
      model of woman-centered care. Consensus among professional and governmental
      groups is that, based on the evidence, intermittent auscultation is safer to use
      in healthy women with uncomplicated pregnancies than electronic fetal monitoring
      (EFM). Barriers impact the laboring woman's ability to give informed choice
      regarding fetal monitoring. Lack of informed choice denies a woman her right to
      be in control of her birth experience, and is in opposition to a woman's right to
      autonomy and self-determination. 

PMID- 24868130
TI  - The birth of joseph gabriel.
AB  - In this column, a mother shares the story of the birth of her first child. With
      confidence in the process of birth and in her ability to give birth, and with the
      support, confidence, and encouragement of her mother and sisters, Anne manages to
      cope with strong contractions through a busy day. Finally, her husband realizes
      how fast labor is progressing. Baby Joseph was born less than 2 hours after
      arrival at the hospital. 

PMID- 24868128
TI  - Self-efficacy and postpartum teaching: a replication study.
AB  - Postpartum depression (PPD) occurs in 13% of new mothers internationally, but
      many do not receive treatment. In the Western world, hospital-based perinatal
      nurses have extended contact with new mothers and are in a unique position to
      teach them to recognize symptoms of and seek treatment for PPD. In this
      replication study framed by self-efficacy theory, teaching new mothers about PPD
      was predicted by a nurse's self-efficacy related to PPD teaching, expectations
      for teaching from supervisor, PPD continuing education, teaching experience on
      other topics, and experience with observing other nurses teaching patients about
      PPD. The results of the study demonstrate the importance of the climate created
      by the nursing supervisor in which teaching about PPD is expected and
      facilitators of effective patient teaching are available. 

PMID- 24868131
TI  - Don't Rush Me . . . Go the Full 40: AWHONN's Public Health Campaign Promotes
      Spontaneous Labor and Normal Birth to Reduce Overuse of Inductions and Cesareans.
AB  - Don't Rush Me . . . Go the Full 40 is a grassroots public health campaign from
      the Association of Women's Health, Obstetric and Neonatal Nursing (AWHONN) that
      educates women about the physiologic benefits of full-term pregnancy for
      themselves and their babies. GoTheFull40.com seeks to increase the percentage of
      women who complete at least 40 weeks of pregnancy, decrease the percentage of
      women who choose elective induction or elective cesarean surgery, and increase
      nurses' and other pregnancy-care providers' effectiveness in reducing the number
      of elective inductions and cesarean surgeries. Childbirth educators and other
      pregnancy providers are asked to share the campaign with women in preconception
      and prenatal settings to encourage waiting for spontaneous labor leading to full
      term births when all is healthy and well with the mother and fetus. 

PMID- 24868132
TI  - Effect of intermittent kangaroo mother care on weight gain of low birth weight
      neonates with delayed weight gain.
AB  - OBJECTIVE: To evaluate intermittent Kangaroo Mother Care (KMC) with additional
      opportunities to breastfeed on weight gain of low birth weight (LBW) neonates
      with delayed weight gain. METHODS: 40 LBW neonates were followed to see whether
      KMC with additional opportunities to breastfeed improved weight gain. RESULTS: In
      the KMC group, the mean age of regaining birth weight was significantly less
      (15.68 vs. 24.56 days) and the average daily weight gain was significantly higher
      (22.09 vs. 10.39 g, p < .001) than controls. CONCLUSION: KMC with additional
      opportunities to breastfeed was found to be an effective intervention for LBWs
      with delayed weight gain and should be considered to be an effective strategy.

PMID- 24868133
TI  - Childrearing among thai first-time teenage mothers.
AB  - The aim of this study is to explore and describe the experiences of being a
      teenage mother and taking care of infants less than 6 months of age. Ten teenage
      mothers were interviewed. Latent content analysis was used to analyze interview
      transcripts with the teenage mothers. It was found that previous childrearing
      experiences and social support were important factors in determining how teenage
      mothers adapted to being a mother and how they practiced infant care. Becoming a
      mother created feelings of responsibility in the maternal role and led to
      affection toward their babies. Nevertheless, teenage mothers appreciated the help
      they received from their families and health-care providers. Instruction and
      assistance with infant care built self-confidence in the maternal role and in
      childrearing. 

PMID- 24868134
TI  - The cesarean decision survey.
AB  - A descriptive study design was used to describe the decision of women having a
      cesarean surgery. The Cesarean Birth Decision Survey was used to collect data
      from 101 postpartum women who underwent a cesarean. Most of the surgeries were to
      primipara women who reported doctor recommendation and increased safety for the
      baby as the main reasons for the cesarean. Those women who had repeat cesarean
      surgery all cited their previous cesarean as the main reason for the current
      surgery. Women's knowledge of cesarean surgery needs to be assessed early in
      pregnancy so that appropriate education may be provided. Accurate and ongoing
      information may decrease the number of women choosing a cesarean surgery. 

PMID- 24868135
TI  - Vicarious birth experiences and childbirth fear: does it matter how young
      canadian women learn about birth?
AB  - In our secondary analysis of a cross-sectional survey, we explored predictors of
      childbirth fear for young women (n = 2,676). Young women whose attitudes toward
      pregnancy and birth were shaped by the media were 1.5 times more likely to report
      childbirth fear. Three factors that were associated with reduced fear of birth
      were women's confidence in reproductive knowledge, witnessing a birth, and
      learning about pregnancy and birth through friends. Offering age-appropriate
      birth education during primary and secondary education, as an alternative to mass
      mediated information about birth, can be evaluated as an approach to reduce young
      women's childbirth fear. 

PMID- 24868136
TI  - Evidence-based maternity care: can new dogs learn old tricks?
AB  - In this article, a Lamaze Certified Childbirth Educator describes her efforts to
      change the culture of birth in a community hospital in a small Midwestern town.
      Her experience highlights the challenges and the frustrations involved in
      creating change. The authors reflect on ways to enhance the success of change and
      advocacy strategies. 

PMID- 24868137
TI  - Pharmacokinetics and retinal toxicity of various doses of intravitreal
      triamcinolone acetonide in rabbits.
AB  - PURPOSE: To compare the pharmacokinetics and retinal toxicity of various doses of
      intravitreal triamcinolone acetonide (TA) in rabbits. METHODS: The rabbits
      received intravitreal injections of 4 mg and 8 mg TA. The drug concentrations
      were determined with high-performance liquid chromatography after extraction from
      the vitreous at various time points. The main pharmacokinetics parameters were
      calculated with 3p97 pharmacokinetics software. The intraocular pressure,
      electroretinography, and pathological examinations were evaluated before and
      after intravitreal injection of different doses of TA. RESULTS: The half-life of
      intravitreal injection of 4 mg and 8 mg TA was 24 days and 34 days, respectively.
      No significant differences were found in intraocular pressure (p>0.05) and the
      electroretinography b-wave amplitudes (p>0.05) among the rabbits before and after
      intravitreal injection of 4 mg and 8 mg TA. Light and electron microscopy did not
      show any retinal damage in any group. CONCLUSIONS: Intravitreal injection of 4 mg
      and 8 mg TA are safe for the rabbit retina. The injection of 8 mg TA produced a
      longer vitreous half-life and had a prolonged effect on the retina. This
      conclusion may be referenced in the clinical application of TA in retinal
      diseases.

PMID- 24868138
TI  - Three-dimensional architecture of collagen type VI in the human trabecular
      meshwork.
AB  - PURPOSE: Type VI collagen is a primary component of the extracellular matrix of
      many connective tissues. It can form distinct aggregates depending on tissue
      structure, chemical environment, and physiology. In the current study we examine
      the ultrastructure and mode of aggregation of type VI collagen molecules in the
      human trabecular meshwork. METHODS: Trabecular meshwork was dissected from donor
      human eyes, and three-dimensional transmission electron microscopy of type VI
      collagen aggregates was performed. RESULTS: Electron-dense collagen structures
      were detected in the human trabecular meshwork and identified as collagen type VI
      assemblies based on the three-dimensional spatial arrangement of the type VI
      collagen molecules, the 105-nm axial periodicity of the assemblies themselves,
      and their characteristic double bands, which arose from the globular domains of
      the type VI collagen molecules. Sulfated proteoglycans were also seen to
      associate with the assemblies either with the globular domain or the inner rod
      like segments of the tetramers. CONCLUSIONS: No extended structural regularity in
      the organization of type VI collagen assemblies within the trabecular meshwork
      was evident, and the lateral separation of the tetramers forming the assemblies
      varied, as did the angle formed by the main axes of adjacent tetramers. This is
      potentially reflective of the specific nature of the trabecular meshwork
      environment, which facilitates aqueous outflow from the eye, and we speculate
      that extracellular matrix ions and proteins might prevent a more tight packing of
      type VI collagen tetramers that form the assemblies.

PMID- 24868139
TI  - The proliferation of malignant melanoma cells could be inhibited by ranibizumab
      via antagonizing VEGF through VEGFR1.
AB  - PURPOSE: Angiogenesis is an important mediator in tumor progression. Vascular
      endothelial growth factor (VEGF) is one of the major cytokines that can influence
      angiogenesis. However, the potential mechanism of tumor growth inhibition through
      anti-VEGF agents is still unclear. This study was performed to examine whether
      ranibizumab could inhibit malignant melanoma growth in vitro and to determine the
      safety of ranibizumab on human adult retinal pigment epithelium cell line (ARPE
      19 cells). METHODS: Malignant melanoma cells obtained from a clinic were cultured
      in vitro. VEGF concentrations secreted by malignant melanoma cells and the ARPE
      19 cells were examined by enzyme-linked immunosorbent assay (ELISA). The two
      kinds of cells were both treated with VEGF and its antagonist, ranibizumab. The
      dynamic changes of the two types of cells were monitored by real-time cell
      electronic sensing (RT-CES) assay. The effect of ranibizumab on both types of
      cells was verified by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl (MTT) assay. The
      expression of VEGF receptor 1 (VEGFR1) RNA in uveal melanoma was further
      investigated through the PCR technique. RESULTS: The levels of VEGF secreted by
      malignant melanoma cells were much higher than those of ARPE-19 cells, and were
      markedly decreased in the action of 0.1 mg/ml ranibizumab. However, there was no
      obvious reduction of VEGF in the presence of ranibizumab for ARPE-19 (p>0.05).
      Meanwhile, RT-CES showed that the viability of malignant melanoma cells increased
      greatly in the presence of VEGF. When VEGF was 20 ng/ml, viability of the
      malignant melanoma cells increased by 40% compared with the negative control.
      There was no evident effect on proliferation of ARPE-19 (p>0.05). Furthermore,
      the growth of malignant melanoma cells was obviously inhibited after ranibizumab
      intervention. When ranibizumab was administered at 0.25 mg/ml, the survival rate
      of the malignant melanoma cells decreased to 57.5%. Nevertheless, low-dose
      exposure to ranibizumab had only a slight effect on the growth of ARPE-19, and
      PCR result demonstrated that VEGFR1 plays a role in this tumor tissue rather than
      VEGFR2. CONCLUSIONS: Ranibizumab can selectively inhibit malignant melanoma cell
      proliferation by decreasing the expression of VEGF; the possible mechanism of the
      inhibitory effect may involve VEGFR1 antagonism.

PMID- 24868141
TI  - Fenton Oxidation Kinetics and Intermediates of Nonylphenol Ethoxylates.
AB  - Removal of nonylphenol ethoxylates (NPEOs) in aqueous solution by Fenton
      oxidation process was studied in a laboratory-scale batch reactor. Operating
      parameters, including initial pH temperature, hydrogen peroxide, and ferrous ion
      dosage, were thoroughly investigated. Maximum NPEOs reduction of 84% was achieved
      within 6 min, under an initial pH of 3.0, 25 degrees C, an H2O2 dosage of 9.74*10
      3 M, and a molar ratio of [H2O2]/[Fe2+] of 3. A modified pseudo-first-order
      kinetic model was found to well represent experimental results. Correlations of
      reaction rate constants and operational parameters were established based on
      experimental data. Results indicated that the Fenton oxidation rate and removal
      efficiency were more dependent on the dosage of H2O2 than Fe2+, and the apparent
      activation energy (DeltaE) was 17.5 kJ/mol. High-performance liquid
      chromatography and gas chromatograph mass spectrometer analytical results
      indicated degradation of NPEOs obtained within the first 2 min stepwise occurred
      by ethoxyl (EO) unit shortening. Long-chain NPEOs mixture demonstrated a higher
      degradation rate than shorter-chain ones. Nonylphenol (NP), short-chain NPEOs,
      and NP carboxyethoxylates were identified as the primary intermediates, which
      were mostly further degraded.

PMID- 24868142
TI  - A UPLC-MS Method for the Determination of Ofloxacin Concentrations in Aqueous
      Humor.
AB  - A rapid, simple, and specific method based on ultra performance liquid
      chromatography (UPLC) with mass spectrometry detection has been developed for
      quantitative analysis of ofloxacin in human aqueous humor using tobramycin as
      internal standard (IS). Chromatographic separation was achieved on a Waters
      Acquity UPLC BEH C18 Shield column (150 * 2.1 mm, 1.7 MUm) eluted with 95:5
      water: acetonitrile (v/v) containing 0.1% formic acid and a flow rate of 0.3
      mL/minute. The total analysis time was three minutes with ofloxacin eluting at
      1.67 +/- 0.03 minutes. The linearity of the method ranged from 0.1 to 8 MUg/mL
      with r2 = 0.998. The method was validated according to FDA guidelines with
      respect to linearity, accuracy, precision, specificity, and stability. The limits
      of detection and quantification were 0.03 and 0.10 MUg/mL, respectively. The
      developed method was successfully applied to the analysis of samples that have
      been obtained from patients. 

PMID- 24868140
TI  - Polymorphisms of DNA repair genes OGG1 and XPD and the risk of age-related
      cataract in Egyptians.
AB  - PURPOSE: To analyze the association of the polymorphisms of xeroderma pigmentosum
      complementation group D (XPD) and 8-oxoguanine glycosylase-1 (OGG1) genes with
      the risk of age-related cataract (ARC) in an Egyptian population. METHODS: This
      case-control study included 150 patients with ARC and 50 controls. Genotyping of
      XPD Asp312Asn was performed by amplification refractory mutation system PCR assay
      and genotyping of OGG1 Ser326Cys was carried out by PCR including confronting two
      pair primers. RESULTS: The Asn/Asn genotype of XPD gene was significantly
      associated with increased risk of ARC (odds ratio [OR] = 2.74, 95% confidence
      interval [CI] = 1.01-7.43, p = 0.04) and cortical cataract (OR = 5.06, 95% CI =
      1.70-15.05, p = 0.002). The Asn312 allele was significantly associated with an
      increased risk of ARC (OR = 1.75, 95% CI 1.06-2.89, p = 0.03) and cortical
      cataract (OR = 2.81, 95% CI = 1.56-5.08, p<0.001). The OGG1 Cys/Cys genotype
      frequency was significantly higher in ARC (OR = 4.13, 95% CI = 0.93-18.21, p =
      0.04) and the Cys(326 allele (OR = 1.85, 95% CI = 1.07-3.20, p = 0.03). Moreover,
      the Cys/Cys genotype of the OGG1 gene was significantly higher in cortical
      cataract (OR = 6.00, 95% CI = 1.24-28.99, p = 0.01) and the Cys326 allele was
      also significantly associated with cortical cataract (OR = 2.45, 95% CI = 1.30
      4.63, p = 0.005). CONCLUSIONS: The results suggest that the Asn/Asn genotype and
      Asn312 allele of XPD polymorphism, as well as the Cys/Cys genotype and Cys326
      allele of the OGG1 polymorphism, may be associated with increased risk of the
      development of ARC, particularly the cortical type, in the Egyptian population.

PMID- 24868143
TI  - Visual and optical performance of diffractive multifocal intraocular lenses with
      different haptic designs: 6 month follow-up.
AB  - PURPOSE: To evaluate and compare the visual acuity outcomes and optical
      performances of eyes implanted with two diffractive multifocal intraocular lens
      (IOL) models with either a plate haptic design or a modified-C design. METHODS:
      This retrospective study comprised cataract patients who were implanted with
      either a plate haptic multifocal IOL model (Acriva(UD) Reviol BB MFM 611 [VSY
      Biotechnology, Amsterdam, the Netherlands], group 1) or a modified-C haptic
      multifocal IOL model (Acriva(UD) Reviol BB MF 613 [VSY Biotechnology, Amsterdam,
      the Netherlands], group 2) between June 2012 and May 2013. The 6 month
      postoperative visual acuity, refraction, defocus curve, contrast sensitivity, and
      wave-front aberration were evaluated and compared between these eyes, using
      different IOL models. RESULTS: One hundred fifty-eight eyes of 107 patients were
      included in this study. Significant improvement in visual acuities and refraction
      was found in both groups after cataract surgery (P<0.01). The visual acuity and
      contrast sensitivity were statistically better in group 1 than in group 2
      (P<0.01). No statistically significant difference in the corneal higher-order
      aberrations was found between the two groups (P>0.05). However, the ocular higher
      order aberrations in group 2 were significantly greater than in group 1 (P<0.05).
      CONCLUSION: At 6 months postoperatively, both Acriva(UD) Reviol BB MFM 611 IOL
      and Acriva(UD) Reviol BB MF 613 IOL achieved excellent visual and refractive
      outcomes. The multifocal IOL model with plate haptic design resulted in better
      optical performances than that with the modified-C haptic design.

PMID- 24868144
TI  - Patient adherence and persistence with topical ocular hypotensive therapy in real
      world practice: a comparison of bimatoprost 0.01% and travoprost Z 0.004%
      ophthalmic solutions.
AB  - BACKGROUND: Effective control of intraocular pressure is predicated upon patient
      compliance with pharmacotherapy. We compared patient adherence and persistence
      with two new ocular hypotensive formulations, using real-world utilization data.
      METHODS: This observational cohort study employed pharmacy claims data from the
      Source((r)) Lx (Wolters Kluwer Pharma Solutions) database. Patients with an
      initial (index) prescription for topical bimatoprost 0.01% or travoprost Z (April
      to June 2011) and no claim for ophthalmic prostaglandin or prostamide analogs
      within the previous 18 months were identified. Treatment adherence was expressed
      as proportion of days covered with study medication during the first 365 days
      after the index prescription. Treatment persistence with study medication was
      assessed over the first 12 months using Kaplan-Meier survival analyses, allowing
      a maximum 30-day gap for prescription refill. Treatment status was determined
      monthly over this period. RESULTS: A total of 12,985 patients were assessed for
      treatment adherence, and 10,470 for treatment persistence. Adherence was better
      with bimatoprost 0.01% than with travoprost Z (mean proportion of days covered
      0.540 versus [vs] 0.486, P<0.001), and more patients showed high adherence
      (proportion of days covered >0.80) with bimatoprost 0.01% than travoprost Z
      (29.1% vs 22.3%, P<0.001). Continuous 12-month persistence was higher with
      bimatoprost 0.01% than with travoprost Z (29.5% vs 24.2%, P<0.001). At month 12,
      more patients were on treatment with bimatoprost 0.01% than travoprost Z (48.8%
      vs 45.7%, P<0.01). Similar findings were demonstrated in cohorts of ocular
      hypotensive treatment-naive patients, branded latanoprost switchers, and older
      patients (age >=65 years), and after inclusion of patient characteristics as
      covariates. CONCLUSION: For patients with glaucoma or ocular hypertension,
      bimatoprost 0.01% offers compliance advantages over travoprost Z.

PMID- 24868145
TI  - Fornix-based versus limbal-based conjunctival flaps in trabeculectomy with
      mitomycin C in high-risk patients.
AB  - PURPOSE: To compare the surgical outcomes of limbal-based and fornix-based
      trabeculectomy in eyes with a history of ocular incisional surgery. METHODS:
      Twenty-six eyes underwent limbal-based trabeculectomy (group LB), and were
      condition matched with 26 eyes that received fornix-based trabeculectomy (group
      FB). Surgical failure was recorded retrospectively if the intraocular pressure
      value was either >=21, >=18, and >=15 mmHg (conditions A, B, and C, respectively)
      or <4 mmHg or if the patient required additional glaucoma surgery. Kaplan-Meier
      survival curve analysis was used to assess surgical failure. RESULTS: For
      condition A, the 2 year surgical success probabilities were 75.0% and 63.9% in
      groups FB and LB, respectively (P=0.124). The corresponding values were 55.0% and
      61.7% (P=0.638) in condition B, and 55.0% and 57.0% (P=0.454) in condition C. The
      rates of bleb leakage, hypotony, choroidal detachment, and bleb-related infection
      were 11.5%, 26.9%, 50.0%, and 7.7% in group LB, respectively. The corresponding
      values in group FB were 30.8%, 23.1%, 46.2%, and 0.0%, which were not
      statistically different between the two groups. CONCLUSION: No significant
      differences in surgical outcomes were observed between limbal-based and fornix
      based trabeculectomy for patients with a history of incisional ocular surgeries.

PMID- 24868146
TI  - Effect of MMX(r) mesalamine coadministration on the pharmacokinetics of
      amoxicillin, ciprofloxacin XR, metronidazole, and sulfamethoxazole: results from
      four randomized clinical trials.
AB  - BACKGROUND: MMX((r)) mesalamine is a once daily oral 5-aminosalicylic acid
      formulation, effective in induction and maintenance of ulcerative colitis
      remission. Patients on long-term mesalamine maintenance may occasionally require
      concomitant antibiotic treatment for unrelated infections. AIM: To evaluate the
      potential for pharmacokinetic interactions between MMX mesalamine and
      amoxicillin, ciprofloxacin extended release (XR), metronidazole, or
      sulfamethoxazole in four open-label, randomized, placebo-controlled, two-period
      crossover studies. METHODS: In all four studies, healthy adults received placebo
      once daily or MMX mesalamine 4.8 g once daily on days 1-4 in one of two treatment
      sequences. In studies 1 and 2, subjects also received a single dose of
      amoxicillin 500 mg (N=62) or ciprofloxacin XR 500 mg (N=30) on day 4. In studies
      3 and 4, subjects received metronidazole 750 mg twice daily on days 1-3 and once
      on day 4 (N=30); or sulfamethoxazole 800 mg/trimethoprim 160 mg twice daily on
      days 1-3 and once on day 4 (N=44). RESULTS: MMX mesalamine had no significant
      effects on systemic exposure to amoxicillin, ciprofloxacin, or metronidazole; the
      90% confidence intervals (CIs) around the geometric mean ratios (antibiotic + MMX
      mesalamine: antibiotic + placebo) for maximum plasma concentration (Cmax) and
      area under the plasma concentration-time curve (AUC) fell within the predefined
      equivalence range (0.80-1.25). Sulfamethoxazole exposure increased by a
      statistically significant amount when coadministered with MMX mesalamine;
      however, increased exposure (by 12% in Cmax at steady state; by 15% in AUC at
      steady state) was not considered clinically significant, as the 90% CIs for each
      point estimate fell entirely within the predefined equivalence range. Adverse
      events in all studies were generally mild. CONCLUSION: MMX mesalamine may be
      coadministered with amoxicillin, ciprofloxacin, metronidazole, or
      sulfamethoxazole, without affecting pharmacokinetics or safety of these
      antibiotics. CLINICALTRIALSGOV IDENTIFIERS: NCT01442688, NCT01402947,
      NCT01418365, and NCT01469637.

PMID- 24868148
TI  - i Engaging as an innovative approach to engage patients in their own fall
      prevention care.
AB  - Decreasing patient fall injuries during hospitalization continues to be a
      challenge at the bedside. Empowering patients to become active participants in
      their own fall prevention care could be a solution. In a previous study, elderly
      patients recently discharged from a United States hospital expressed a need for
      nurses to give and repeat directives about fall prevention; when the nurse left a
      brochure on the topic, but did not provide any (or limited) verbal explanations
      about the content or the importance of the information, the patient felt that the
      information was insufficient. To address patients' needs, we developed "i
      Engaging", a Web-based software application for use at the bedside. i Engaging is
      an innovative approach that is used to engage patients in their own fall
      prevention care during hospital stays. The application was designed based on the
      assumption that patients are the best and most critical sources of information
      about their health status. i Engaging has not yet been tested in clinical trials.

PMID- 24868147
TI  - Protective effect of picroside II on myocardial ischemia reperfusion injury in
      rats.
AB  - The aim of this study was to determine the effect of picroside II on myocardial
      ischemia reperfusion injury in rats and to explore its underlying mechanism.
      Isolated rat hearts underwent 30 minutes of global ischemia followed by 120
      minutes of reperfusion. Different doses of picroside II (1 MUM, 10 MUM, and 100
      MUM) were given 20 minutes before ischemia. Phosphoinositide 3-kinase inhibitor
      (wortmannin) and nitric oxide synthase (NOS) inhibitor (L-N(G)-nitroarginine
      methyl ester) were given 10 minutes before picroside II treatment. The cardiac
      function, myocardial infarct size, apoptosis, myocardial nitric oxide content,
      the expressions of Bcl-2 and Bax, and the activation of the phosphoinositide 3
      kinase/Akt/endothelial NOS pathway were evaluated. Treatment with 10 MUM and 100
      MUM picroside II significantly improved postischemic myocardial function, reduced
      myocardial infarct size, inhibited apoptosis, increased myocardial NO content,
      upregulated Bcl-2, downregulated Bax, and increased the phosphorylation of Akt
      and endothelial NOS, but cardioprotection was not shown in the 1 MUM picroside II
      treatment group and was abrogated by wortmannin and L-N(G)-nitroarginine methyl
      ester. Furthermore, cardioprotection in the 100 MUM picroside II treatment group
      was superior to that in the 10 MUM picroside II treatment group. In conclusion,
      the data reveals that picroside II has a significant protective effect on
      myocardial ischemia reperfusion injury in a dose-dependent manner, which was
      mediated by upregulating the phosphoinositide 3-kinase/Akt/endothelial NOS
      pathway to increase nitric oxide production and regulating the expressions of Bcl
      2 and Bax to inhibit apoptosis. 

PMID- 24868149
TI  - Approaches to improve adherence to pharmacotherapy in patients with
      schizophrenia.
AB  - PURPOSE: In patients with schizophrenia, nonadherence to prescribed medications
      increases the risk of patient relapse and hospitalization, key contributors to
      the costs associated with treatment. The objectives of this review were to
      evaluate the impact of nonadherence to pharmacotherapy in patients with
      schizophrenia as it relates to health care professionals, particularly social
      workers, and to identify effective team approaches to supporting patients based
      on studies assessing implementation of assertive community treatment teams.
      MATERIALS AND METHODS: A systematic review of the medical literature was
      conducted by searching the Scopus database to identify articles associated with
      treatment adherence in patients with schizophrenia. Articles included were
      published from January 1, 2003, through July 15, 2013, were written in English,
      and reported findings concerning any and all aspects of nonadherence to
      prescribed treatment in patients with schizophrenia. RESULTS: Of 92 unique
      articles identified and formally screened, 47 met the inclusion criteria for the
      systematic review. The burden of nonadherence in schizophrenia is significant.
      Factors with the potential to affect adherence include antipsychotic drug class
      and formulation, patient-specific factors, and family/social support system.
      There is inconclusive evidence suggesting superior adherence with an atypical
      versus typical antipsychotic or with a long-acting injectable versus an oral
      formulation. Patient-specific factors that contribute to adherence include
      awareness/denial of illness, cognitive issues, stigma associated with taking
      medication, substance abuse, access to health care, employment/poverty, and
      insurance status. Lack of social or family support may adversely affect
      adherence, necessitating the assistance of health care professionals, such as
      social workers. Evidence supports the concept that an enhanced team-oriented
      approach to managing patients with schizophrenia improves adherence and supports
      corresponding reductions in relapse rates, inpatient admissions, and associated
      costs. CONCLUSION: Optimization of medication and involvement of caregivers are
      important to promoting adherence. A multidisciplinary team approach may be
      invaluable in identifying barriers to adherence and helping schizophrenia
      patients overcome them.

PMID- 24868150
TI  - Comparison of factors influencing patient choice of community pharmacy in Poland
      and in the UK, and identification of components of pharmaceutical care.
AB  - BACKGROUND: Several factors, which are components of pharmaceutical care, can
      influence a patient's choice of a community pharmacy store and contribute to
      frequent visits to the same pharmacy. OBJECTIVES: To compare factors that
      influence a patient's choice of pharmacy in Poland and in the UK, to identify
      which of them are components of pharmaceutical care, and to relate them to
      patient loyalty to the same pharmacy. METHODS: A self-administered, anonymous
      questionnaire was distributed to clients visiting pharmacies in Poland and the UK
      January-August 2011. Comparisons were performed using chi-square tests and
      logistic regression. All statistical analyses were performed using SPSS 20.0.
      RESULTS: The response rate was 55.6% (n=417/750; 36 pharmacies) and 54.0%
      (n=405/750; 56 pharmacies) in Poland and in the UK, respectively. The most
      frequently reported factors, as defined by a percentage of responders, were in
      Poland: 1) location (84%); 2) professional and high-quality of service (82%); 3)
      good price of medicines (78%); and 4) promotions on medicines (66%). In the UK,
      the most commonly reported factors were: 1) professional and high quality of
      service (90%); 2) location (89%); 3) good advice received from the pharmacist
      (86%); and 4) option of discussing and consulting all health issues in a
      consultation room (80%). Good advice and an option of discussing personal
      concerns with a pharmacist are components of pharmaceutical care. Thirty-eight
      percent of patients in Poland and 61% in the UK declared visiting the same
      pharmacy. CONCLUSION: Components of pharmaceutical care are important factors
      influencing the patient's choice of pharmacy in the UK and, to a lesser degree,
      in Poland. Additionally, more patients in the UK than in Poland are committed to
      a single pharmacy. Therefore, implementing the full pharmaceutical care in Poland
      may contribute to an increase in patient loyalty and thus strengthen
      competitiveness of pharmacy businesses.

PMID- 24868151
TI  - Development of comorbidity-adapted exercise protocols for patients with knee
      osteoarthritis.
AB  - BACKGROUND: Exercise therapy is generally recommended for patients with
      osteoarthritis (OA) of the knee. Comorbidity, which is highly prevalent in OA,
      may interfere with exercise therapy. To date, there is no evidence-based protocol
      for the treatment of patients with knee OA and comorbidity. Special protocols
      adapted to the comorbidity may facilitate the application of exercise therapy in
      patients with knee OA and one or more comorbidities. PURPOSE: The purpose of this
      study was to develop comorbidity-adapted exercise protocols for patients with
      knee OA and comorbidity. METHOD: Several steps were undertaken to develop
      comorbidity-adapted protocols: selection of highly prevalent comorbidities in OA,
      a literature search to identify restrictions and contraindications for exercise
      therapy for the various comorbid diseases, consultation of experts on each
      comorbid disease, and field testing of the protocol in eleven patients with knee
      OA and comorbidity. RESULTS: Based on literature and expert opinion, comorbidity
      adapted protocols were developed for highly prevalent comorbidities in OA. Field
      testing showed that the protocols provided guidance in clinical decision making
      in both the diagnostic and the treatment phase. Because of overlap, the number of
      exercise protocols could be reduced to three: one for physiological adaptations
      (coronary disease, heart failure, hypertension, diabetes type 2, chronic
      obstructive pulmonary diseases, obesity), one for behavioral adaptations (chronic
      a-specific pain, nonspecific low back pain, depression), and one for
      environmental adaptations (visual or hearing impairments). Evaluation of patient
      outcome after treatment showed significant (P<0.05) and clinically relevant
      improvements in activity limitations and pain. CONCLUSION: Comorbidity-adapted
      exercise protocols for patients with knee OA were developed, providing guidance
      in clinical reasoning with regard to diagnostics and treatment. To evaluate the
      effectiveness of treatment in line with our protocols, a randomized clinical
      trial should be performed.

PMID- 24868152
TI  - Efficacy of treatment for hyperglycemic crisis in elderly diabetic patients in a
      day hospital.
AB  - BACKGROUND: The purpose of this prospective cohort study was to compare the costs
      of day hospital (DH) care for hyperglycemic crisis in elderly diabetic patients
      with those of conventional hospitalization (CH). Secondary objectives were to
      compare these two clinical scenarios in terms of glycemic control, number of
      emergency and outpatient visits, readmissions, hypoglycemic episodes, and
      nosocomial morbidity. METHODS: The study population comprised diabetic patients
      aged >74 years consecutively admitted to a tertiary teaching hospital in Spain
      for hyperglycemic crisis (sustained hyperglycemia [>300 mg/dL] for at least 3
      days with or without ketosis). The patients were assigned to DH or CH care
      according to time of admission and were followed for 6 months after discharge.
      Exclusion criteria were ketoacidosis, hyperosmolar crisis, hemodynamic
      instability, severe intercurrent illness, social deprivation, or Katz index >D.
      RESULTS: Sixty-four diabetic patients on DH care and 36 on CH care were included,
      with no differences in baseline characteristics. The average cost per patient was
      1,345.1+/-793.6 ? in the DH group and 2,212.4+/-982.5 ? in the CH group
      (P<0.001). There were no differences in number of subjects with mild hypoglycemia
      during follow-up (45.3% DH versus 33.3% CH, P=0.24), nor in the percentage of
      patients achieving a glycated hemoglobin (HbA(1c)) <8% (67.2% DH versus 58.3% CH,
      P=0.375). Readmissions for hyperglycemic crisis and pressure ulcer rates were
      significantly higher in the CH group. CONCLUSION: DH care for hyperglycemic
      crises is more cost-effective than CH care, with a net saving of 1,418.4 ? per
      case, lower number of readmissions and pressure ulcer rates, and similar short
      term glycemic control and hypoglycemia rates.

PMID- 24868153
TI  - Efficacy of bronchoscopic lung volume reduction: a meta-analysis.
AB  - BACKGROUND: Over the last several years, the morbidity, mortality, and high costs
      associated with lung volume reduction (LVR) surgery has fuelled the development
      of different methods for bronchoscopic LVR (BLVR) in patients with emphysema. In
      this meta-analysis, we sought to study and compare the efficacy of most of these
      methods. METHODS: ELIGIBLE STUDIES WERE RETRIEVED FROM PUBMED AND EMBASE FOR THE
      FOLLOWING BLVR METHODS: one-way valves, sealants (BioLVR), LVR coils, airway
      bypass stents, and bronchial thermal vapor ablation. Primary study outcomes
      included the mean change post-intervention in the lung function tests, the 6
      minute walk distance, and the St George's Respiratory Questionnaire. Secondary
      outcomes included treatment-related complications. RESULTS: Except for the airway
      bypass stents, all other methods of BLVR showed efficacy in primary outcomes.
      However, in comparison, the BioLVR method showed the most significant findings
      and was the least associated with major treatment-related complications. For the
      BioLVR method, the mean change in forced expiratory volume (in first second) was
      0.18 L (95% confidence interval [CI]: 0.09 to 0.26; P<0.001); in 6-minute walk
      distance was 23.98 m (95% CI: 12.08 to 35.88; P<0.01); and in St George's
      Respiratory Questionnaire was -8.88 points (95% CI: -12.12 to -5.64; P<0.001).
      CONCLUSION: The preliminary findings of our meta-analysis signify the importance
      of most methods of BLVR. The magnitude of the effect on selected primary outcomes
      shows noninferiority, if not equivalence, when compared to what is known for
      surgical LVR.

PMID- 24868154
TI  - Does the duration of smoking cessation have an impact on hospital admission and
      health-related quality of life amongst COPD patients?
AB  - BACKGROUND: Lack of awareness among ex-smokers on the benefits of sustaining
      smoking cessation may be the main cause of their smoking relapse. This study
      explored health-related quality of life (HRQoL) and hospital admission amongst
      chronic obstructive pulmonary disease (COPD) patients according to the duration
      of smoking cessation. MATERIALS AND METHODS: This study recruited COPD patients
      from a chest clinic who agreed to participate in a medication therapy-adherence
      program from January to June 2013. They were interviewed during their visits to
      obtain information regarding their smoking history and HRQoL. They were divided
      into three groups according to smoking status (sustained quitters, quit >=5
      years; quitters, quit <5 years; and smokers, smoking at least one cigarette/day).
      The effects of the duration of cessation on HRQoL and hospital admission were
      analyzed using a multinomial logistic model. RESULTS: A total of 117 participants
      with moderate COPD met the inclusion criteria, who were comprised of 41 sustained
      quitters, 40 quitters, and 36 smokers. Several features were similar across the
      groups. Most of them were married elderly men (aged >64 years) with low-to-middle
      level of education, who smoked more than 33 cigarettes per day and had high
      levels of adherence to the medication regimen. The results showed that sustained
      quitters were less likely to have respiratory symptoms (cough, phlegm and
      dyspnea) than smokers (odds ratio 0.02, confidence interval 0-0.12; P<0.001). The
      hospital admission rate per year was increased in quitters compared to smokers
      (odds ratio 4.5, confidence interval 1.91-10.59; P<0.005). CONCLUSION: A longer
      duration of quitting smoking will increase the benefits to COPD patients, even if
      they experience increased episodic respiratory symptoms in the early period of
      the cessation. Thus, the findings of this study show the benefits of early
      smoking cessation.

PMID- 24868156
TI  - Factors associated with body image distortion in Korean adolescents.
AB  - PURPOSE: Body image incorporates cognitive and affective components as well as
      behaviors related to own body perception. This study evaluated the occurrence of
      body image distortion and its correlates in Korean adolescents. METHODS: In a
      school-based cross-sectional survey, a total of 2,117 adolescents were recruited.
      They filled out self-completing questionnaires on body image distortion, eating
      attitudes, and behaviors (Eating Attitude Test-26) and related factors. RESULTS:
      Body image distortions were found in 51.8 percent of adolescents. Univariate
      analyses showed that boys and older adolescents had higher rates of body image
      distortion. In the multivariate analyses, body image distortion was associated
      with high risk for eating disorders (odds ratio [OR] =1.69; 95% confidence
      interval [CI] 1.11-2.58; P=0.015) and being over weight (OR =33.27; 95% CI 15.51
      71.35; P<0.001) or obese (OR =9.37; 95% CI 5.06-17.34; P<0.001). CONCLUSION:
      These results suggest that body image distortion is relatively common in Korean
      adolescents, which has implications for adolescents at risk of developing eating
      disorders.

PMID- 24868155
TI  - Biological augmentation of rotator cuff repair using bFGF-loaded electrospun
      poly(lactide-co-glycolide) fibrous membranes.
AB  - Clinically, rotator cuff tear (RCT) is among the most common shoulder
      pathologies. Despite significant advances in surgical techniques, the re-tear
      rate after rotator cuff (RC) repair remains high. Insufficient healing capacity
      is likely the main factor for reconstruction failure. This study reports on a
      basic fibroblast growth factor (bFGF)-loaded electrospun poly(lactide-co
      glycolide) (PLGA) fibrous membrane for repairing RCT. Implantable biodegradable
      bFGF-PLGA fibrous membranes were successfully fabricated using emulsion
      electrospinning technology and then characterized and evaluated with in vitro and
      in vivo cell proliferation assays and repairs of rat chronic RCTs. Emulsion
      electrospinning fabricated ultrafine fibers with a core-sheath structure which
      secured the bioactivity of bFGF in a sustained manner for 3 weeks. Histological
      observations showed that electrospun fibrous membranes have excellent
      biocompatibility and biodegradability. At 2, 4, and 8 weeks after in vivo RCT
      repair surgery, electrospun fibrous membranes significantly increased the area of
      glycosaminoglycan staining at the tendon-bone interface compared with the control
      group, and bFGF-PLGA significantly improved collagen organization, as measured by
      birefringence under polarized light at the healing enthesis compared with the
      control and PLGA groups. Biomechanical testing showed that the electrospun
      fibrous membrane groups had a greater ultimate load-to-failure and stiffness than
      the control group at 4 and 8 weeks. The bFGF-PLGA membranes had the highest
      ultimate load-to-failure, stiffness, and stress of the healing enthesis, and
      their superiority compared to PLGA alone was significant. These results
      demonstrated that electrospun fibrous membranes aid in cell attachment and
      proliferation, as well as accelerating tendon-bone remodeling, and bFGF-loaded
      PLGA fibrous membranes have a more pronounced effect on tendon-bone healing.
      Therefore, augmentation using bFGF-PLGA electrospun fibrous membranes is a
      promising treatment for RCT. 

PMID- 24868157
TI  - Risk factors for an anxiety disorder comorbidity among Thai patients with bipolar
      disorder: results from the Thai Bipolar Disorder Registry.
AB  - BACKGROUND: The aim of the study was to determine in a clinical setting the risk
      factors for current anxiety disorder (AD) comorbidity among Thai patients with
      bipolar disorder (BD), being treated under the Thai Bipolar Disorder Registry
      Project (TBDR). METHODS: The TBDR was a multisite naturalistic study conducted at
      24 psychiatric units (ie, at university, provincial mental, and government
      general hospitals) between February 2009 and January 2011. Participants were in-
      or out-patients over 18 years of age who were diagnosed with BD according to the
      Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition.
      Instruments used in this study included the Thai Mini International
      Neuropsychiatric Interview version 5; Thai Montgomery-Asberg Depression Rating
      Scale (MADRS); Thai Young Mania Rating Scale; Clinical Global Impression of
      Bipolar Disorder-Severity (CGI-BP-S), CGI-BP-S-mania, CGI-BPS-depression, and CGI
      BP-S-overall BP illness; and the Thai SF-36 quality of life questionnaire.
      RESULTS: Among the 424 BD patients, 404 (95.3%) had BD type I. The respective
      mean +/- standard deviation of age of onset of mood disturbance, first diagnosis
      of BD, and first treatment of BD was 32.0+/-11.9, 36.1+/-12.2, and 36.2+/-12.2
      years. The duration of illness was 10.7+/-9.0 years. Fifty-three (12.5%) of the
      424 participants had a current AD while 38 (9%) had a substance use disorder
      (SUD). The univariate analysis revealed 13 significant risks for current AD
      comorbidity, which the multivariate analysis narrowed to age at first diagnosis
      of BD (odds ratio =0.95, P<0.01), family history of SUD (odds ratio =2.18,
      P=0.02), and having a higher current MADRS score (odds ratio =1.11, P<0.01).
      CONCLUSION: A diagnosis of AD comorbid with BD is suggested by early-age onset of
      BD together with a higher MADRS score and a family history of SUD. The likelihood
      of AD comorbidity decreases by 5% with each passing year; early-age onset of BD
      is a risk while later age onset is protective. Our results underscore how SUD
      within the family significantly contributes to the risk of an AD comorbidity.

PMID- 24868158
TI  - The association between suicide risk and self-esteem in Japanese university
      students with major depressive episodes of major depressive disorder.
AB  - BACKGROUND: The suicide risk among young adults is related to multiple factors;
      therefore, it is difficult to predict and prevent suicidal behavior. AIM: We
      conducted the present study to reveal the most important factors relating to
      suicidal ideation in Japanese university students with major depressive episodes
      (MDEs) of major depressive disorder (MDD). METHODS: The subjects were 30 Japanese
      university students who had MDEs of MDD, and were aged between 18 and 26 years
      old. They were divided into two groups - without suicide risk group (n=15), and
      with suicide risk group (n=15) - based on the results of the Mini-International
      Neuropsychiatric Interview. Additionally, healthy controls were recruited from
      the same population (n=15). All subjects completed the self-assessment scales
      including the Beck Depression Inventory 2nd edition (BDI-II), the Beck
      Hopelessness Scale (BHS), Rosenberg's Self-Esteem Scale (RSES), and SF-36v2TM
      (The Medical Outcomes Study 36-item short-form health survey version 2), and they
      were all administered a battery of neuropsychological tests. RESULTS: The RSES
      score of the suicide risk group was significantly lower than the RSES score of
      the without suicide risk group, whereas the BDI-II score and the BHS score were
      not significantly different between the two groups. The mean social functioning
      score on the SF-36v2 of the with suicide risk group was significantly lower than
      that of the without suicide risk group. CONCLUSION: The individual's self-esteem
      and social functioning may play an important role in suicide risk among young
      adults with MDEs of MDD.

PMID- 24868159
TI  - Nerve growth factor variations in patients with mood disorders: no changes in
      eight weeks of clinical treatment.
AB  - BACKGROUND: Nerve growth factor (NGF) has received much attention for its role in
      mood disorders. The primary objective of the present study was to examine serum
      NGF levels in Chinese inpatients with depressive or manic episodes in the acute
      phase and to explore the changes in NGF levels after effective clinical
      treatments. METHODS: One hundred and seven consecutive inpatients and outpatients
      with mood disorders (30 with unipolar depression, 23 with bipolar depression, and
      54 with bipolar mania), and 50 healthy controls were recruited. The serum NGF
      levels were detected by enzyme-linked immunosorbent assay. RESULTS: Patients with
      bipolar mania presented higher serum NGF levels compared to those of healthy
      controls. After 8 weeks of medical treatment, there were significant improvements
      in symptoms in patients, but no significant changes in NGF levels. CONCLUSION:
      The present findings may help to strengthen and expand the understanding of the
      role of NGF in the acute stages of mood disorders.

PMID- 24868160
TI  - Udenafil for the treatment of erectile dysfunction.
AB  - Erectile dysfunction (ED) is often perceived by both patients and sexual partners
      as a serious problem that can jeopardize quality of life, psychosocial or
      emotional well-being, and the partnership in the long term. Since their
      introduction, oral phosphodiesterase type 5 inhibitors (PDE5Is) have been found
      to be highly effective and well tolerated, and are available as the first-line
      therapy for the treatment of ED. Udenafil is one of the selective PDE5Is made
      available in recent years for the treatment of ED. Udenafil has clinical
      properties of both relatively rapid onset and long duration of action due to its
      pharmacokinetic profile, thereby providing an additional treatment option for ED
      men to better suit individual needs. There is positive evidence that udenafil is
      effective and well tolerated in the treatment of ED of a broad spectrum of
      etiologies or severity. Udenafil is as effective in the treatment of diabetes
      mellitus-associated ED as other PDE5Is. Due to the clinical property of
      relatively long duration of action, udenafil may be another option in daily
      dosing treatment for ED, as suggested by its favorable efficacy and safety
      profile. Most adverse effects reported from clinical trials are mild or moderate
      in severity, without any serious adverse event, with headache and flushing being
      the most common. Also, the concomitant use of anti-hypertensive drugs or alpha-1
      blockers does not significantly affect the efficacy and safety profile of
      udenafil. However, additional studies with larger cohorts including prospective,
      multicenter, comparative studies with patients of different ethnicities are
      needed to further validate the favorable findings of udenafil in the treatment of
      ED. 

PMID- 24868161
TI  - Management of malignant hyperthermia: diagnosis and treatment.
AB  - Malignant hyperthermia is a potentially lethal inherited disorder characterized
      by disturbance of calcium homeostasis in skeletal muscle. Volatile anesthetics
      and/or the depolarizing muscle relaxant succinylcholine may induce this
      hypermetabolic muscular syndrome due to uncontrolled sarcoplasmic calcium release
      via functionally altered calcium release receptors, resulting in hypoxemia,
      hypercapnia, tachycardia, muscular rigidity, acidosis, hyperkalemia, and
      hyperthermia in susceptible individuals. Since the clinical presentation of
      malignant hyperthermia is highly variable, survival of affected patients depends
      largely on early recognition of the symptoms characteristic of malignant
      hyperthermia, and immediate action on the part of the attending anesthesiologist.
      Clinical symptoms of malignant hyperthermia, diagnostic criteria, and current
      therapeutic guidelines, as well as adequate management of anesthesia in patients
      susceptible to malignant hyperthermia, are discussed in this review. 

PMID- 24868162
TI  - Validation of the custo screen 400 ambulatory blood pressure-monitoring device
      according to the European Society of Hypertension International Protocol revision
      2010.
AB  - OBJECTIVE: The aim of the present study was to validate the custo screen 400
      ambulatory blood pressure-monitoring (ABPM) device according to the 2010
      International Protocol revision of the European Society of Hypertension (ESH-IP).
      The device can be used for ABPM for up to 72 hours. MATERIALS AND METHODS:
      Systolic and diastolic blood pressure (SBP and DBP, respectively) were
      sequentially measured in 33 adult subjects (13 males and 20 females) and compared
      with a standard mercury sphygmomanometer (two observers). A total of 99
      comparison pairs were obtained. RESULTS: The custo screen 400 met the
      requirements of parts 1 and 2 of the ESH-IP revision 2010. The mean difference
      between the device and reference sphygmomanometer readings was -0.5+/-4.5 mmHg
      for SBP and -0.1+/-3.3 mmHg for DBP. All but one measurement were within the
      absolute difference of 10 mmHg between the device and the observers for SBP and
      DBP. The number of absolute differences between the device and the observers
      within a range of 5 mmHg was 84 of 99 readings for SBP, and 93 of 99 readings for
      DBP. CONCLUSION: The custo screen 400 ABPM device met the requirements of the
      2010 ESH-IP revision, and hence can be recommended for ABPM in adults. To our
      knowledge, the custo screen 400 is the first device to pass the revised ESH-IP
      2010.

PMID- 24868163
TI  - Blood and urine levels of heavy metal pollutants in female and male patients with
      coronary artery disease.
AB  - BACKGROUND: Heavy metal pollutants such as cadmium (Cd), lead (Pb), and mercury
      (Hg) are rarely the subjects of cardiovascular research although they have been
      suspected for decades to negatively impact the circulatory system. METHODS: Apart
      from detailed anamnestic data, urinary levels of Cd and full blood levels of Pb
      and Hg were measured in 53 female (mean age: 68.04+/-7.03 years) and 111 male
      (mean age: 60.68+/-11.43 years) nonsmoking or never-smoking patients with
      angiographically verified and precisely quantified coronary artery disease (CAD).
      RESULTS: Although Cd was quantifiable in 68.3% of subjects, only 34.1% of these
      patients exceeded the critical 1 MUg/L Human Biomonitoring (HBM)-I level. Median
      Pb (20 MUg/L) and Hg (0.55 MUg/L) levels were lower than the HBM-I, as well as
      reference levels of Pb. Wine consumption was the main source for Pb, fish and
      wine consumption for Hg, and previous nicotine abuse for Cd. There was no
      correlation between Cd, Pb, or Hg and severity of CAD although severity
      correlated positively with atherosclerosis parameters (uric acid, creatinine,
      triglycerides, blood urea nitrogen, C-reactive protein) and negatively with high
      density lipoprotein cholesterol. CONCLUSION: Cd levels detected in CAD patients
      were high compared to German and European reference levels but it could not be
      proven that urine levels of Cd and blood levels of Hg or Pb played a major role
      in the genesis of CAD, particularly when compared to well-known biomarkers such
      as blood pressure, glucose, and lipids.

PMID- 24868165
TI  - The community-based Health Extension Program significantly improved contraceptive
      utilization in West Gojjam Zone, Ethiopia.
AB  - BACKGROUND: Ethiopia has implemented a nationwide primary health program at
      grassroots level (known as the Health Extension Program) since 2003 to increase
      public access to basic health services. This study was conducted to assess
      whether households that fully implemented the Health Extension Program have
      improved current contraceptive use. METHODS: A cross-sectional community-based
      survey was conducted to collect data from 1,320 mothers using a structured
      questionnaire. A multivariate logistic regression was used to identify the
      predictors of current contraceptive utilization. A propensity score analysis was
      used to determine the contribution of the Health Extension Program "model
      households" on current contraceptive utilization. RESULT: Mothers from households
      which fully benefited from the Health Extension Program ("model households") were
      3.97 (adjusted odds ratio, 3.97; 95% confidence interval, 3.01-5.23) times more
      likely to use contraceptives compared with mothers from non-model households.
      Model household status contributed to 29.3% (t=7.08) of the increase in current
      contraceptive utilization. CONCLUSION: The Health Extension Program when
      implemented fully could help to increase the utilization of contraceptives in the
      rural community and improve family planning.

PMID- 24868164
TI  - Rivaroxaban in patients with a recent acute coronary syndrome event: integration
      of trial findings into clinical practice.
AB  - Despite significant advances in the management of acute coronary syndrome (ACS)
      and long-term antiplatelet therapy after an ACS event, patients continue to be at
      risk of further cardiovascular events. There is evidence that recurrent events
      are at least partly attributed to the persistent activation of the coagulation
      system after ACS. Various anticoagulants, including vitamin K antagonists (VKAs)
      and non-VKA oral anticoagulants, have been evaluated in patients post-ACS, in
      combination with antiplatelet therapy. The desired outcome would be a further
      reduction of recurrent cardiovascular events with low or acceptable levels of
      bleeding complications. Here, we provide an overview of the current clinical
      trial data of non-VKA oral anticoagulants, focusing on rivaroxaban in particular,
      for secondary prevention in patients with a recent ACS event. 

PMID- 24868166
TI  - IL-17A (-197G/A) and IL-17F (7488T/C) gene polymorphisms and cancer risk in Asian
      population: a meta-analysis.
AB  - Interleukin (IL)-17 has been shown to play an important role in the pathogenesis
      of inflammation and cancer. The IL-17A (-197G/A) and IL-17F (7488T/C)
      polymorphisms have been extensively investigated with cancer risk, but
      individually published results have been inconclusive. The aim of this study was
      to clarify the effects of the IL-17A (-197G/A) and IL-17F (7488T/C) polymorphisms
      on cancer risk in Asian populations. Relevant studies were identified by
      searching databases extensively. The association between the IL-17A (-197G/A) and
      IL-17F (7488T/C) polymorphisms and cancer risk was assessed by odds ratios (ORs)
      together with their 95% confidence intervals (CIs). A total of 12 articles with
      adequate information satisfied our inclusion criteria; these included 12 studies,
      with 4,540 cases and 5,875 controls, of IL-17A (-197G/A) polymorphism and seven
      studies, with 1,960 cases and 3,226 controls, of IL-17F (7488T/C) polymorphism.
      In the overall analysis, the IL-17A (-197G/A) polymorphism was significantly
      associated with increased cancer risk (P<0.05), for all genetic models. However,
      there was no statistically significant association between IL-17F (7488T/C) and
      cancer risk (P>0.05), for any genetic models. Furthermore, stratification by
      cancer type revealed a significant correlation between the IL-17A (-197G/A)
      polymorphism and cancer risk for all cancer types. When stratified by source of
      controls, a significant correlation was observed between the IL-17A (-197G/A)
      polymorphism and cancer risk in the population-based control subgroup but not in
      hospital-based control subgroup. In conclusion, our meta-analysis provides
      evidence that the IL-17A (-197G/A) polymorphism might be associated with cancer
      risk, while no evidence suggested a significant association between IL-17F
      (7488T/C) polymorphism and cancer risk. 

PMID- 24868167
TI  - Prognostic value of pretreatment serum levels of lactate dehydrogenase in
      nonmetastatic nasopharyngeal carcinoma: single-site analysis of 601 patients in a
      highly endemic area.
AB  - BACKGROUND: Numerous studies have generated promising but incomplete evidence for
      the prognostic value of pretreatment serum levels of lactate dehydrogenase (S
      LDH) in nasopharyngeal carcinoma (NPC). METHODS: Pretreatment serum levels of S
      LDH in 601 patients with NPC were measured before treatment, and their
      associations with overall survival and tumor-free survival were studied.
      Univariate and multivariate analysis of subgroups was used to evaluate the
      prognostic value of S-LDH in early-stage and late-stage NPC separately. RESULTS:
      Pretreatment S-LDH levels were significantly lower in T1+2 patients than in T3+4
      patients, lower in N0+1 patients than in N2+3 ones, and lower in stage I + II
      patients than in III + IV ones. Multivariate analysis showed that among patients
      with late-stage NPC, high pretreatment S-LDH levels >225 U/L were an independent
      predictor of poor overall survival and tumor-free survival. Among patients with
      early-stage NPC, pretreatment S-LDH levels >171 U/L, which overlap with the
      normal range, were an independent predictor of shorter overall survival and tumor
      free survival. CONCLUSION: Pretreatment S-LDH levels may be a reliable biomarker
      for predicting the long-term prognosis of patients with early-stage or late-stage
      NPC.

PMID- 24868170
TI  - Calcium supplementation after parathyroidectomy in dialysis and renal transplant
      patients.
AB  - BACKGROUND: Data on the risk factors and clinical course of hungry bone syndrome
      are lacking in dialysis and renal transplant patients who undergo
      parathyroidectomy. In this study, we aimed to assess the risks and clinical
      course of hungry bone syndrome and calcium repletion after parathyroidectomy in
      dialysis and renal transplant patients. METHODS: We performed a retrospective
      review of parathyroidectomies performed at The Nebraska Medical Center. RESULTS:
      We identified 41 patients, ie, 30 (73%) dialysis and eleven (27%) renal
      transplant patients. Dialysis patients had a significantly higher pre-surgery
      intact parathyroid hormone (iPTH, P<0.001) and a larger iPTH drop after surgery
      (P<0.001) than transplant recipients. Post-surgery hypocalcemia in dialysis
      patients was severe and required aggressive and prolonged calcium replacement (11
      g) versus a very mild hypocalcemia requiring only brief and minimal replacement
      (0.5 g) in transplant recipients (P<0.001). Hypophosphatemia was not detected in
      the dialysis group. Phosphorus did not increase immediately after surgery in
      transplant recipients. The hospital stay was significantly longer in dialysis
      patients (8.2 days) compared with transplant recipients (3.2 days, P<0.001).
      CONCLUSION: The clinical course of hungry bone syndrome is more severe in
      dialysis patients than in renal transplant recipients. Young age, elevated
      alkaline phosphatase, elevated pre-surgery iPTH, and a large decrease in post
      surgical iPTH are risk factors for severe hungry bone syndrome in dialysis
      patients.

PMID- 24868169
TI  - Renal artery stenosis: epidemiology and treatment.
AB  - Renal artery stenosis (RAS) is a frequently encountered problem in clinical
      practice. The disease encompasses a broad spectrum of pathophysiologies and is
      associated with three major clinical syndromes: ischemic nephropathy,
      hypertension, and destabilizing cardiac syndromes. The two most common etiologies
      are fibromuscular dysplasia and atherosclerotic renal artery disease with
      atherosclerotic disease accounting for the vast majority of cases.
      Atherosclerotic renovascular disease has considerable overlap with
      atherosclerotic disease elsewhere and is associated with a poor prognosis. A wide
      range of diagnostic modalities and treatment approaches for RAS are available to
      clinicians, and with the advent of endovascular interventions, selecting the best
      course for a given patient has only grown more challenging. Several clinical
      trials have demonstrated some benefit with revascularization but not to the
      extent that many had hoped for or expected. Furthermore, much of the existing
      data is only marginally useful given significant flaws in study design and
      inherent bias. There remains a need for further identification of subgroups and
      appropriate indications in hopes of maximizing outcomes and avoiding unnecessary
      procedures in patients who would not benefit from treatment. In recent decades,
      the study of RAS has expanded and evolved rapidly. In this review, we will
      attempt to summarize the amassed body of literature with a focus on the
      epidemiology of RAS including prevalence, overlap with other atherosclerotic
      disease, and prognosis. We will also outline existing diagnostic and treatment
      approaches available to clinicians as well as summarize the findings of several
      major clinical trials. Finally, we will offer our perspective on future
      directions in the field. 

PMID- 24868171
TI  - Possible impact of the CYP2D6*10 polymorphism on the nonlinear pharmacokinetic
      parameter estimates of paroxetine in Japanese patients with major depressive
      disorders.
AB  - It has been suggested that the reduced function allele with reduced cytochrome
      P450 (CYP) 2D6 activity, CYP2D6*10, is associated with the interindividual
      differences in the plasma paroxetine concentrations, but there is no data
      presently available regarding the influence of the CYP2D6*10 polymorphism on the
      pharmacokinetic parameters, eg, Michaelis-Menten constant (Km) and maximum
      velocity (Vmax), in Asian populations. The present study investigated the effects
      of the CYP2D6 polymorphisms, including CYP2D6*10, on the pharmacokinetic
      parameters of paroxetine in Japanese patients with major depressive disorders.
      This retrospective study included 15 Japanese patients with major depressive
      disorders (four males and eleven females) who were treated with paroxetine. The
      CYP2D6*2, CYP2D6*4, CYP2D6*5, CYP2D6*10, CYP2D6*18, CYP2D6*39, and CYP2D6*41
      polymorphisms were evaluated. A total of 56 blood samples were collected from the
      patients. The Km and Vmax values of paroxetine were estimated for each patient.
      The allele frequencies of CYP2D6*2, CYP2D6*4, CYP2D6*5, CYP2D6*10, CYP2D6*18,
      CYP2D6*39, and CYP2D6*41 were 6.7%, 0%, 10.0%, 56.7%, 0%, 26.7%, and 0%,
      respectively. The mean values of Km and Vmax were 50.5+/-68.4 ng/mL and 50.6+/
      18.8 mg/day, respectively. Both the Km and Vmax values were significantly smaller
      in CYP2D6*10 allele carriers than in the noncarriers (24.2+/-18.3 ng/mL versus
      122.5+/-106.3 ng/mL, P=0.008; 44.2+/-16.1 mg/day versus 68.3+/-15.0 mg/day,
      P=0.022, respectively). This is the first study to demonstrate that the CYP2D6*10
      polymorphism could affect the nonlinear pharmacokinetic parameter estimates of
      paroxetine in Asian populations. The findings of this study suggest that the
      CYP2D6*10 polymorphism may be associated with the smaller values of both the Km
      and Vmax in Japanese patients with major depressive disorders, and these results
      need to be confirmed in further investigations with a larger number of patients. 

PMID- 24868168
TI  - State of the art in advanced endoscopic imaging for the detection and evaluation
      of dysplasia and early cancer of the gastrointestinal tract.
AB  - Ideally, endoscopists should be able to detect, characterize, and confirm the
      nature of a lesion at the bedside, minimizing uncertainties and targeting
      biopsies and resections only where necessary. However, under conventional white
      light inspection - at present, the sole established technique available to most
      of humanity - premalignant conditions and early cancers can frequently escape
      detection. In recent years, a range of innovative techniques have entered the
      endoscopic arena due to their ability to enhance the contrast of diseased tissue
      regions beyond what is inherently possible with standard white-light endoscopy
      equipment. The aim of this review is to provide an overview of the state-of-the
      art advanced endoscopic imaging techniques available for clinical use that are
      impacting the way precancerous and neoplastic lesions of the gastrointestinal
      tract are currently detected and characterized at endoscopy. The basic
      instrumentation and the physics behind each method, followed by the most
      influential clinical experience, are described. High-definition endoscopy, with
      or without optical magnification, has contributed to higher detection rates
      compared with white-light endoscopy alone and has now replaced ordinary equipment
      in daily practice. Contrast-enhancement techniques, whether dye-based or
      computed, have been combined with white-light endoscopy to further improve its
      accuracy, but histology is still required to clarify the diagnosis. Optical
      microscopy techniques such as confocal laser endomicroscopy and endocytoscopy
      enable in vivo histology during endoscopy; however, although of invaluable
      assistance for tissue characterization, they have not yet made transition between
      research and clinical use. It is still unknown which approach or combination of
      techniques offers the best potential. The optimal method will entail the ability
      to survey wide areas of tissue in concert with the ability to obtain the degree
      of detailed information provided by microscopic techniques. In this respect, the
      challenging combination of autofluorescence imaging and confocal endomicroscopy
      seems promising, and further research is awaited. 

PMID- 24868173
TI  - Advances in evaluating the fetal skeleton.
AB  - In this review, we discuss aspects of the prenatal diagnosis of fetal skeletal
      malformations, concentrating on the advantages offered by different imaging
      techniques and the approaches that are of value in evaluating a suspected
      skeletal dysplasia. We also briefly address the findings in some of the commoner
      malformations of the fetal skeleton that may be encountered. 

PMID- 24868172
TI  - Seroprevalence of human papillomavirus immunoglobulin G antibodies among women
      presenting at the reproductive health clinic of a university teaching hospital in
      Nigeria.
AB  - BACKGROUND: Human papillomavirus (HPV) is the cause of 90%-95% of squamous cell
      cancers. Persistent infection with high-risk HPV can lead to development of
      precancerous lesions of the cervix in 5%-10% of infected women, and can progress
      to invasive cervical cancer 15-20 years later. This study was conducted to
      determine the seroprevalence of HPV immunoglobulin G (IgG) antibodies among women
      of reproductive age attending a reproductive health clinic at Ahmadu Bello
      University Teaching Hospital, Zaria, Nigeria. METHODS: The study was descriptive,
      cross-sectional, and experimental, combining the use of a structured
      questionnaire and analysis of serum samples obtained from 350 consecutive
      consenting women. The serum samples were analyzed for IgG antibodies to HPV by
      enzyme-linked immunosorbent assay. RESULTS: We found a seroprevalence of 42.9%
      (150/350) for IgG antibodies to HPV in these women. Women aged 45-49 years and
      those who had their sexual debut aged 20-23 years had the highest HPV
      seroprevalence, ie, 50% (57/114) and 51.1% (46/90), respectively. Presence of
      antibodies varied according to sociodemographic factors, but was significantly
      associated with educational status, tribe, and religion (P<0.05). Human
      papillomavirus infection was not significantly associated with the reproductive
      characteristics and sexual behavior of the women. Antibodies to HPV were detected
      in 50.0% (9/18) of women with a family history of cervical cancer and in 30.8%
      (4/13) of those with a history or signs of WHIM (warts, hypogammaglobulinemia,
      immunodeficiency, myelokathexis) syndrome as a genetic disorder (P>0.05).
      CONCLUSION: Further studies are needed to determine the HPV serotypes and
      evaluate the risk of natural development of HPV-related malignancies among women
      in the study area.

PMID- 24868174
TI  - The value of 3D and 4D assessments of the fetal heart.
AB  - The objective of this review was to demonstrate the main tools of three- and four
      dimensional ultrasonography, using the spatiotemporal image correlation software
      and its respective applications for assessing the fetal heart and its vascular
      connections, along with its potential contribution towards screening for
      congenital heart diseases. Today, conventional, two-dimensional, echocardiography
      continues to be the gold standard for diagnosing congenital heart diseases.
      However, recent studies have demonstrated that spatiotemporal image correlation
      offers some advantages that boost two-dimensional accuracy in detecting
      congenital heart diseases, given that the fetal heart assessment can be completed
      in the absence of the patient (offline) and be discussed by different examiners.
      Additionally, data volumes can be sent for analysis in reference centers via
      internet links. Spatiotemporal image correlation also enables direct measurement
      of heart structures in rendering mode, such as the interventricular septum and
      the annulus of the atrioventricular valves. Furthermore, it enables assessment of
      cardiac function when used in association with the virtual organ computer-aided
      analysis software, thus making it possible to calculate the total systolic
      function, ejection fraction, and cardiac output. 

PMID- 24868175
TI  - Evaluation of a minimally invasive procedure for sacroiliac joint fusion - an in
      vitro biomechanical analysis of initial and cycled properties.
AB  - INTRODUCTION: Sacroiliac (SI) joint pain has become a recognized factor in low
      back pain. The purpose of this study was to investigate the effect of a minimally
      invasive surgical SI joint fusion procedure on the in vitro biomechanics of the
      SI joint before and after cyclic loading. METHODS: SEVEN CADAVERIC SPECIMENS WERE
      TESTED UNDER THE FOLLOWING CONDITIONS: intact, posterior ligaments (PL) and pubic
      symphysis (PS) cut, treated (three implants placed), and after 5,000 cycles of
      flexion-extension. The range of motion (ROM) in flexion-extension, lateral
      bending, and axial rotation was determined with an applied 7.5 N . m moment using
      an optoelectronic system. Results for each ROM were compared using a repeated
      measures analysis of variance (ANOVA) with a Holm-Sidak post-hoc test. RESULTS:
      Placement of three fusion devices decreased the flexion-extension ROM. Lateral
      bending and axial rotation were not significantly altered. All PL/PS cut and post
      cyclic ROMs were larger than in the intact condition. The 5,000 cycles of flexion
      extension did not lead to a significant increase in any ROMs. DISCUSSION: In the
      current model, placement of three 7.0 mm iFuse Implants significantly decreased
      the flexion-extension ROM. Joint ROM was not increased by 5,000 flexion-extension
      cycles.

PMID- 24868176
TI  - "Brain drain" and "brain waste": experiences of international medical graduates
      in Ontario.
AB  - BACKGROUND: "Brain drain" is a colloquial term used to describe the migration of
      health care workers from low-income and middle-income countries to higher-income
      countries. The consequences of this migration can be significant for donor
      countries where physician densities are already low. In addition, a significant
      number of migrating physicians fall victim to "brain waste" upon arrival in
      higher-income countries, with their skills either underutilized or not utilized
      at all. In order to better understand the phenomena of brain drain and brain
      waste, we conducted an anonymous online survey of international medical graduates
      (IMGs) from low-income and middle-income countries who were actively pursuing a
      medical residency position in Ontario, Canada. METHODS: Approximately 6,000
      physicians were contacted by email and asked to fill out an online survey
      consisting of closed-ended and open-ended questions. The data collected were
      analyzed using both descriptive statistics and a thematic analysis approach.
      RESULTS: A total of 483 IMGs responded to our survey and 462 were eligible for
      participation. Many were older physicians who had spent a considerable amount of
      time and money trying to obtain a medical residency position. The top five
      reasons for respondents choosing to emigrate from their home country were:
      socioeconomic or political situations in their home countries; better education
      for children; concerns about where to raise children; quality of facilities and
      equipment; and opportunities for professional advancement. These same reasons
      were the top five reasons given for choosing to immigrate to Canada. Themes that
      emerged from the qualitative responses pertaining to brain waste included
      feelings of anger, shame, desperation, and regret. CONCLUSION: Respondents
      overwhelmingly held the view that there are not enough residency positions
      available in Ontario and that this information is not clearly communicated to
      incoming IMGs. Brain waste appears common among IMGs who immigrate to Canada and
      should be made a priority for Canadian policy-makers.

PMID- 24868177
TI  - Effect of shortened Integrated Management of Childhood Illness training on
      classification and treatment of under-five children seeking care in Rwanda.
AB  - BACKGROUND: Integrated Management of Childhood Illness (IMCI) is an effective 11
      day standard training; however, due to budgetary expenses and human resource
      constraints, many health professionals cannot take 11 days off work. As a result,
      shortened training curriculums (6-day) have been proposed. We used a cross
      sectional study to evaluate the effect of this shortened training on appropriate
      IMCI classification and treatment of under-five childhood illness management in
      Rwanda. METHODS: A cross-sectional study was conducted in 22 health centers in
      Rwanda, comparing data from 121 nurses, where 55 nurses completed the 11-day and
      66 nurses completed the 6-day training. Among 768 children, we evaluated clinical
      outcomes from May 2011 to April 2012. Descriptive statistics were used to display
      the sociodemographic characteristics of health providers; including level of
      education, sex, age, and professional experiences. Bivariable and multivariable
      analyses were used to test for differences between nurses in the 6-day versus 11
      day training on the appropriate classification and treatment of childhood
      illness. RESULTS: Our findings show that at the bivariable level and after
      controlling for confounders in the multivariable analysis, the only significant
      differences detected between nurses in the long and short training was the
      classification of fever (adjusted odds ratio [aOR] 0.7, 95% confidence interval
      [CI] 0.64-0.75) and treatment of pneumonia (aOR 0.8, 95% CI 0.70-0.89). Nurses in
      the short training had lower odds of inappropriate misclassification and
      treatment for these two conditions. CONCLUSION: There was no difference in
      classification and treatment of childhood illness among nurses who completed the
      standard and short IMCI training courses. Short-training could be a more cost
      saving option for health facilities without compromising the key outcomes related
      to case management.

PMID- 24868178
TI  - A survey of the attitudes and beliefs about the use of TENS for pain management
      by physiotherapists working in two cities in Sri Lanka.
AB  - INTRODUCTION: Transcutaneous electrical nerve stimulation (TENS) is a
      noninvasive, inexpensive, self-administered technique used throughout the world
      to relieve pain. In Sri Lanka, physiotherapists may use TENS for their patients
      as they receive a small amount of education about the principles and practice of
      TENS in their undergraduate training. To date, there have been no data gathered
      about the use of TENS by physiotherapists in Sri Lanka. The aim of this study was
      to assess attitudes and beliefs of physiotherapists working in Sri Lanka about
      their use of TENS for pain management. METHODS: A postal survey was undertaken
      using a 12-item questionnaire developed by the investigators to gather
      information about attitudes, beliefs and use of TENS in clinical practice. The
      questionnaire was distributed to 100 physiotherapists working in three government
      hospitals and six private hospitals in the cities of Kandy and Colombo. A
      descriptive analysis of data was performed. RESULTS: Sixty-seven completed
      questionnaires were returned (67% response rate). Over half of the respondents
      (58.2%) reported that they used TENS to treat pain "often" or "very often", with
      use for musculoskeletal/orthopedic (61.3%) and neuropathic/neuralgic (79.1%) pain
      being most common. TENS was used less for postsurgical pain and rarely for cancer
      pain. Most (95.5%) respondents reported that their patients benefitted
      "considerably" from TENS. 76.1% of the respondents reported that they did not
      recommend and/or prescribe TENS for patients to use at home. CONCLUSION:
      Physiotherapists value TENS as a treatment option to manage musculoskeletal and
      neuropathic pain. However, there is a need for systems and resources to enable to
      patients to self-administer TENS rather than having to visit clinics.

PMID- 24868179
TI  - Fatal carboplatin-induced immune hemolytic anemia in a child with a brain tumor.
AB  - Drug-induced immune hemolytic anemia (DIIHA) is an uncommon side effect of
      pharmacologic intervention. A rare mediator of DIIHA, carboplatin is an agent
      used to treat many pediatric cancers. We describe here, the first case of fatal
      carboplatin induced DIIHA in a pediatric patient and a brief review of the
      literature. Our patient developed acute onset of multi-organ failure with
      evidence of complement activation, secondary to a drug induced red cell antibody.
      Early recognition of the systemic insult associated with carboplatin induced
      hemolytic anemia may allow for future affected patients to receive
      plasmapheresis, a potentially effective therapy. 

PMID- 24868180
TI  - The Picmonic((r)) Learning System: enhancing memory retention of medical
      sciences, using an audiovisual mnemonic Web-based learning platform.
AB  - BACKGROUND: Medical students are required to retain vast amounts of medical
      knowledge on the path to becoming physicians. To address this challenge,
      multimedia Web-based learning resources have been developed to supplement
      traditional text-based materials. The Picmonic((r)) Learning System (PLS;
      Picmonic, Phoenix, AZ, USA) is a novel multimedia Web-based learning platform
      that delivers audiovisual mnemonics designed to improve memory retention of
      medical sciences. METHODS: A single-center, randomized, subject-blinded,
      controlled study was conducted to compare the PLS with traditional text-based
      material for retention of medical science topics. Subjects were randomly assigned
      to use two different types of study materials covering several diseases. Subjects
      randomly assigned to the PLS group were given audiovisual mnemonics along with
      text-based materials, whereas subjects in the control group were given the same
      text-based materials with key terms highlighted. The primary endpoints were the
      differences in performance on immediate, 1 week, and 1 month delayed free-recall
      and paired-matching tests. The secondary endpoints were the difference in
      performance on a 1 week delayed multiple-choice test and self-reported
      satisfaction with the study materials. Differences were calculated using unpaired
      two-tailed t-tests. RESULTS: PLS group subjects demonstrated improvements of 65%,
      161%, and 208% compared with control group subjects on free-recall tests
      conducted immediately, 1 week, and 1 month after study of materials,
      respectively. The results of performance on paired-matching tests showed an
      improvement of up to 331% for PLS group subjects. PLS group subjects also
      performed 55% greater than control group subjects on a 1 week delayed multiple
      choice test requiring higher-order thinking. The differences in test performance
      between the PLS group subjects and the control group subjects were statistically
      significant (P<0.001), and the PLS group subjects reported higher overall
      satisfaction with the material. CONCLUSION: The data of this pilot site
      demonstrate marked improvements in the retention of disease topics when using the
      PLS compared with traditional text-based materials. The use of the PLS in medical
      education is supported.

PMID- 24868181
TI  - Factors associated with clinical inertia: an integrative review.
AB  - Failure to initiate or intensify therapy according to evidence-based guidelines
      is increasingly being acknowledged as a phenomenon that contributes to inadequate
      management of chronic conditions, and is referred to as clinical inertia.
      However, the number and complexity of factors associated with the clinical
      reasoning that underlies the decision-making processes in medicine calls for a
      critical examination of the consistency of the concept. Indeed, in the absence of
      information on and justification of treatment decisions that were made, clinical
      inertia may be only apparent, and actually reflect good clinical practice. This
      integrative review seeks to address the factors generally associated with
      clinical inaction, in order to better delineate the concept of true clinical
      inertia. 

PMID- 24868182
TI  - Laser therapy in bone repair in rats: analysis of bone optical density.
AB  - OBJECTIVE: To investigate, by digital radiology, the bone regeneration process in
      rats submitted to femoral osteotomy and treated with low power laser therapy.
      METHODS: Forty-five Wistar rats were subjected to transverse osteotomy of the
      right femur and divided randomly into three experimental groups (n = 15): animals
      not treated with laser therapy G (C), animals that received laser therapy with
      lambda: 660nm G (660nm) and animals that received laser therapy with lambda:
      830nm G (830nm). Animals were sacrificed after 7, 14 and 21 days. The bone
      calluses were evaluated by digital X-ray at 65 kVp, 7mA and 0.032 s exposures.
      RESULTS: The values obtained were submitted to variance analysis (ANOVA) followed
      by the Tukey-Kramer test. The significance level adopted was 5%. The groups G
      (C), G (660nm), and G (830nm) at the 7(th) day showed a significant bone
      development, with p <0.0116; the groups G (C), G (660nm), and G (830nm) at the
      14(th) day showed values of p <0.0001; at the 21(st) day,a higher degree of bone
      repair were observed in group G (830nm), and G (660nm), with p <0.0169.
      CONCLUSION: Based on the radiographic findings, G (830nm) showed more complete
      bone regeneration, as shown in the gray shades of the images. Level of Evidence
      II, Individual Study With Experimental Design.

PMID- 24868183
TI  - A manual method to obtain platelet rich plasma.
AB  - OBJECTIVE: This study is to report a manual method to obtain platelet rich plasma
      (PRP). METHODS: For this study 61 ml of peripheral blood was obtained and
      submitted to centrifugation at 541g for 5 min. The centrifugation separates the
      blood into three components: red blood cells, buffy coat and platelet rich
      plasma. Blood and platelet rich plasma samples were sent to the Hospital's
      Laboratory and platelets and leukocytes were measured. RESULTS: A sample of 637
      blood donors was evaluated. The platelet yield efficiency was 86.77% and the
      increase in platelet concentration factor was 2.89 times. The increase in
      leukocyte concentration factor was 1.97 times. CONCLUSION: The method described
      here produces leukocyte-rich and platelet-rich plasma with a high platelet and
      leukocyte increased factor. Level of Evidence IV, Controlled Laboratory Study.

PMID- 24868184
TI  - Comparison between different radiographic methods for evaluating the flexibility
      of scoliosis curves.
AB  - OBJECTIVE: To compare different radiographic methods of spine evaluation to
      estimate the reducibility and flexibility of the scoliosis curves. METHODS:
      Twenty one patients with Lenke types I and III adolescent idiopathic scoliosis
      (AIS) were included. Radiographic evaluations were made preoperatively on the
      orthostatic, supine decubitus with lateral inclination to the right and left and
      supine positions with manual reduction, with support in the apex of each curve on
      the X-ray table. On the day of surgery, when the patient was anesthetized,
      radiography was taken with longitudinal traction through divergent forces,
      holding under the arms and ankles, and with translational force at the apex of
      the deformity for curve correction. After one week, a post-operative radiography
      was performed in orthostatic position. RESULTS: The correction and flexibility of
      the main thoracic and thoracic/lumbar curves were statistically different between
      the supine radiographs, manual reduction, modified traction under general
      anesthesia, lateral inclination and postoperatively. The modified maneuver for
      traction under general anesthesia is the one which showed greater flexibility,
      besides presenting higher radiographic similarity to postoperative aspects.
      CONCLUSION: Among the radiographic modalities evaluated the study under
      anesthesia with traction and reduction showed better correlation with
      postoperative radiographic appearance. Level of Evidence IV, Case Series.

PMID- 24868185
TI  - Influence of exercises on patellar height in women with patellofemoral pain
      syndrome.
AB  - OBJECTIVE: To evaluate the patellar height of volunteers with and without
      patellofemoral pain syndrome (PPS) during maximal voluntary isometric contraction
      (MVIC) in open kinetic chain (OKC) and closed kinetic chain (CKC) exercises.
      METHODS: Twenty healthy women, and nineteen women with patellofemoral pain
      syndrome were evaluated and subjected to nuclear magnetic resonance imaging
      during rest and MVIC in OKC and CKC at 15 degrees , 30 degrees , and 45 degrees 
      knee flexion. The patellar height was assessed by the K-Pacs program,using the
      Insall-Salvati index. For each exercise and knee position, patellar height was
      measured three times and the procedure was repeated after seven days. RESULTS:
      These data did not confirm our hypothesis that OKC exercises promote increased
      patellar height. CONCLUSION: Patellar height is not associated with PPS and
      suggests that CKC exercises lead an increased patellar height during knee
      position at 15o and 45o flexion for the PPS group. Level of Evidence II,
      Comparative Prospective.

PMID- 24868186
TI  - Extensor digitorum brevis flap on the treatment of lower limb injuries.
AB  - OBJECTIVE: To describe our pioneer national experience with 11 patients with soft
      tissue defects in the distal 1/3 of the leg, ankle and forefoot treated with
      extensor digitorum brevis muscle flap (EDB). METHODS: Between November 2009 and
      July 2012 11 patients were operated with the flap technique. We operated nine men
      and two women aged between 10 and 66 years. The surgical indications were acute
      trauma in four patients and post-traumatic osteomyelitis in seven patients. The
      small defects were covered ranging from 3x3 to 6x3 cm. The patch was applied with
      proximal stalk in most cases. RESULTS: Complete healing and infectious cure were
      obtained in all cases, despite one loss. CONCLUSION: The EDB flap is a feasible
      and safe technique to repair foot, ankle and distal leg losses. Suffering,
      dehiscence and delayed healing of the EDB end flap donor area may, however,
      occur. L-shaped incisions should be avoided for muscle lifting. Level of Evidence
      IV, Case series.

PMID- 24868187
TI  - Epidemiologic study of ankle fractures in a tertiary hospital.
AB  - OBJECTIVES: To evaluate the epidemiology of ankle fractures surgically treated at
      the Instituto de Ortopedia e Traumatologia do Hospital das Clinicas da
      Universidade de Sao Paulo. METHODS: Medical records of patients admitted with
      foot and ankle fractures between 2006 and 2011 were revised. Seventy three ankle
      fractures that underwent surgical treatment were identified. The parameters
      analyzed included age, gender, injured side, AO and Gustilo & Anderson
      classification, associated injuries, exposure, need to urgent treatment, time to
      definitive treatment and early post-operative complications. STUDY DESIGN:
      retrospective epidemiological study. RESULTS: Male gender was predominant among
      subjects and the mean age was 27.5 years old. Thirty nine fractures resulted from
      traffic accidents and type B fracture according to AO classification was the most
      common. Twenty one were open fractures and 22 patients had associated injuries.
      The average time to definitive treatment was 6.5 days. Early post-operative
      complications were found in 21.3% of patients. CONCLUSIONS: Ankle fractures
      treated in a tertiary hospital of a large city in Brazil affect young people
      victims of high-energy accidents and present significant rates of associated
      injuries and post-operative complications. Level of Evidence IV, Cases Series.

PMID- 24868188
TI  - Minimal invasive ostheosintesis for treatment of diaphiseal transverse humeral
      shaft fractures.
AB  - OBJECTIVE: To evaluate patients with transverse fractures of the shaft of the
      humerus treated with indirect reduction and internal fixation with plate and
      screws through minimally invasive technique. METHODS: Inclusion criteria were
      adult patients with transverse diaphyseal fractures of the humerus closed,
      isolated or not occurring within 15 days of the initial trauma. Exclusion
      criteria were patients with compound fractures. RESULTS: In two patients,
      proximal screw loosening occurred, however, the fractures consolidated in the
      same mean time as the rest of the series. Consolidation with up to 5 degrees of
      varus occurred in five cases and extension deficit was observed in the patient
      with olecranon fracture treated with tension band, which was not considered as a
      complication. There was no recurrence of infection or iatrogenic radial nerve
      injury. CONCLUSION: It can be concluded that minimally invasive osteosynthesis
      with bridge plate can be considered a safe and effective option for the treatment
      of transverse fractures of the humeral shaft. Level of Evidence III, Therapeutic
      Study.

PMID- 24868189
TI  - Prevalence of acute diseases in the elderly assisted in emergency department of
      orthopedics.
AB  - OBJECTIVE: To make an analysis of the care of elderly in an Emergency Department
      of Orthopedics with the primary objective to know the percentage of elderly
      treated, their conditions of origin and level of accidental conditions, and
      examine possible comorbidities, evolution and mortality rate. METHODS:
      Retrospective observational epidemiological study based on survey records of a
      tertiary hospital during one year (January to December 2006). RESULTS: In the
      year 2006 (January to December) 12,916 calls to patients older than 60 were
      performed. CONCLUSION: Massive attendance of the elderly population was observed,
      however, the vast majority related to chronic problems that do not require urgent
      attention. Patients requiring urgent attention suffer from trauma related to
      falls and are between the seventh and ninth decades of life, mostly female and
      requiring hospitalization for longer periods. Level of Evidence VI, Cases Series.

PMID- 24868190
TI  - Health economics and health preference concepts to orthopedics practitioners.
AB  - The aim of this study was to describe concepts of health economics in order to
      update and provide the orthopedic practitioner decision making parameters based
      on preferences. Four basic types of studies of economical evaluation were
      presented (cost minimization analysis, cost-benefit, cost-effectiveness and cost
      utility), as well as the origin, the concept, advantages and disadvantages of
      using QALY and utility. It was discussed the importance of costs and of SF-6D, an
      instrument able to get through the utility data from the Medical Outcomes Study
      36-item Short Form Health Survey (SF-36). Physicians, especially orthopedic
      practitioners, are increasingly using technologies which are progressively
      expensive, thus, they should be able to understand health economics concepts, the
      importance of utility in clinical decision making process and economic analysis
      in health.09+ 

PMID- 24868192
TI  - Collaborative agency to support integrated care for children, young people and
      families: an action research study.
AB  - INTRODUCTION: Collaboration was legislated in the delivery of integrated care in
      the early 2000s in the UK. This research explored how the reality of practice met
      the rhetoric of collaboration. THEORY: The paper is situated against a
      theoretical framework of structure, agency, identity and empowerment.
      Collectively and contextually these concepts inform the proposed model of
      'collaborative agency' to sustain integrated care. The paper brings sociological
      theory on structure and agency to the dilemma of collaboration. METHODS:
      Participative action research was carried out in collaborative teams that aspired
      to achieve integrated care for children, young people and families between 2009
      and 2013. It was a part time, PhD study in collaborative practice. RESULTS: The
      research established that people needed to be able to be jointly aware of their
      context, to make joint decisions, and jointly act in order to deliver integrated
      services, and proposes a model of collaborative agency derived from
      practitioner's experiences and integrated action research and literature on
      agency. The model reflects the effects of a range of structures in shaping
      professional identity, empowerment, and agency in a dynamic. The author proposes
      that the collaborative agency model will support integrated care, although this
      is, as yet, an untested hypothesis.

PMID- 24868193
TI  - Care transitions for frail, older people from acute hospital wards within an
      integrated healthcare system in England: a qualitative case study.
AB  - INTRODUCTION: Frail older people experience frequent care transitions and an
      integrated healthcare system could reduce barriers to transitions between
      different settings. The study aimed to investigate care transitions of frail
      older people from acute hospital wards to community healthcare or community
      hospital wards, within a system that had vertically integrated acute hospital and
      community healthcare services. THEORY AND METHODS: The research design was a
      multimethod, qualitative case study of one healthcare system in England; four
      acute hospital wards and two community hospital wards were studied in depth. The
      data were collected through: interviews with key staff (n = 17); focus groups (n
      = 9) with ward staff (n = 36); interviews with frail older people (n = 4). The
      data were analysed using the framework approach. FINDINGS: THREE THEMES ARE
      PRESENTED: Care transitions within a vertically integrated healthcare system,
      Interprofessional communication and relationships; Patient and family involvement
      in care transitions. DISCUSSION AND CONCLUSIONS: A vertically integrated
      healthcare system supported care transitions from acute hospital wards through
      removal of organisational boundaries. However, boundaries between staff in
      different settings remained a barrier to transitions, as did capacity issues in
      community healthcare and social care. Staff in acute and community settings need
      opportunities to gain better understanding of each other's roles and build
      relationships and trust.

PMID- 24868194
TI  - Hospital discharge of elderly patients to primary health care, with and without
      an intermediate care hospital - a qualitative study of health professionals'
      experiences.
AB  - INTRODUCTION: Intermediate care is an organisational approach to improve the
      coordination of health care services between health care levels. In Central
      Norway an intermediate care hospital was established in a municipality to improve
      discharge from a general hospital to primary health care. The aim of this study
      was to investigate how health professionals experienced hospital discharge of
      elderly patients to primary health care with and without an intermediate care
      hospital. METHODS: A qualitative study with data collected through semi
      structured focus groups and individual interviews. RESULTS: Discharge via the
      intermediate care hospital was contrasted favourably compared to discharge
      directly from hospital to primary health care. Although increased capacity to
      receive patients from hospital and prepare them for discharge to primary health
      care was viewed as a benefit, professionals still requested better communication
      with the preceding care level concerning further treatment and care for the
      elderly patients. CONCLUSIONS: The intermediate care hospital reduced the
      coordination challenges during discharge of elderly patients from hospital to
      primary health care. Nevertheless, the intermediate care was experienced more
      like an extension of hospital than an included part of primary health care and
      did not meet the need for communication across care levels.

PMID- 24868195
TI  - Breakdown in informational continuity of care during hospitalization of older
      home-living patients: a case study.
AB  - INTRODUCTION: The successful transfer of an older patient between health care
      organizations requires open communication between them that details relevant and
      necessary information about the patient's health status and individual needs. The
      objective of this study was to identify and describe the process and content of
      the patient information exchange between nurses in home care and hospital during
      hospitalization of older home-living patients. METHODS: A multiple case study
      design was used. Using observations, qualitative interviews and document reviews,
      the total patient information exchange during each patient's episode of
      hospitalization (n = 9), from day of admission to return home, was captured.
      RESULTS: Information exchange mainly occurred at discharge, including a discharge
      note sent from hospital to home care, and telephone reports from hospital nurse
      to home care nurse, and meetings between hospital nurse and patient coordinator
      from the municipal purchaser unit. No information was provided from the home care
      nurses to the hospital nurses at admission. Incompleteness in the content of both
      written and verbal information was found. Information regarding physical care was
      more frequently reported than other caring dimensions. Descriptions of the
      patients' subjective experiences were almost absent and occurred only in the
      verbal communication. CONCLUSIONS: The gap in the information flow, as well as
      incompleteness in the content of written and verbal information exchanged,
      constitutes a challenge to the continuity of care for hospitalized home-living
      patients. In order to ensure appropriate nursing follow-up care, we emphasize the
      need for nurses to improve the information flow, as well as to use a more
      comprehensive approach to older patients, and that this must be reflected in the
      verbal and written information exchange.

PMID- 24868196
TI  - Quality in transitional care of the elderly: Key challenges and relevant
      improvement measures.
AB  - INTRODUCTION: Elderly people aged over 75 years with multifaceted care needs are
      often in need of hospital treatment. Transfer across care levels for this patient
      group increases the risk of adverse events. The aim of this paper is to establish
      knowledge of quality in transitional care of the elderly in two Norwegian
      hospital regions by identifying issues affecting the quality of transitional care
      and based on these issues suggest improvement measures. METHODOLOGY: Included in
      the study were elderly patients (75+) receiving health care in the municipality
      admitted to hospital emergency department or discharged to community health care
      with hip fracture or with a general medical diagnosis. Participant observations
      of admission and discharge transitions (n = 41) were carried out by two
      researchers. RESULTS: SIX MAIN CHALLENGES WITH BELONGING DESCRIPTIONS HAVE BEEN
      IDENTIFIED: (1) next of kin (bridging providers, advocacy, support, information
      brokering), (2) patient characteristics (level of satisfaction, level of
      insecurity, complex clinical conditions), (3) health care personnel's competence
      (professional, system, awareness of others' roles), (4) information exchange
      (oral, written, electronic), (5) context (stability, variability, change
      incentives, number of patient handovers) and (6) patient assessment (complex
      clinical picture, patient description, clinical assessment). CONCLUSION: Related
      to the six main challenges, several measures have been suggested to improve
      quality in transitional care, e.g. information to and involvement of patients and
      next of kin, staff training, standardisation of routines and inter-organisational
      staff meetings.

PMID- 24868197
TI  - The French Society of Geriatrics and Gerontology position paper on the concept of
      integration.
AB  - INTRODUCTION: The concept of integration, although dating from the 1990s, has
      only recently appeared in French public health policy. It must be linked with
      'coordination', which is the base of most French public policies applied to
      geriatrics since the 1960s. Herein, we report the French Society of Geriatrics
      and Gerontology working group's findings according to three axes: definition of
      integration, objectives of this organisational approach and the means needed to
      achieve them. DISCUSSION: Integration is a process that aims to overcome the
      fragmentation of services for vulnerable people. This process requires a
      multilevel approach, particularly concerning how to modify public policies and
      financing systems. Notably, all relevant levels need to develop shared processes,
      tools, resources, financing, interventions and action-reports on the latter.
      Integration must be accompanied by a local dedicated professional (the 'pilot').
      Results of recent experiments showed that it is possible to implement integrative
      dynamics in France.

PMID- 24868198
TI  - Integrated care in France: dream or reality?

PMID- 24868199
TI  - A sequential Monte Carlo framework for haplotype inference in CNV/SNP genotype
      data.
AB  - Copy number variations (CNVs) are abundant in the human genome. They have been
      associated with complex traits in genome-wide association studies (GWAS) and
      expected to continue playing an important role in identifying the etiology of
      disease phenotypes. As a result of current high throughput whole-genome single
      nucleotide polymorphism (SNP) arrays, we currently have datasets that
      simultaneously have integer copy numbers in CNV regions as well as SNP genotypes.
      At the same time, haplotypes that have been shown to offer advantages over
      genotypes in identifying disease traits even though available for SNP genotypes
      are largely not available for CNV/SNP data due to insufficient computational
      tools. We introduce a new framework for inferring haplotypes in CNV/SNP data
      using a sequential Monte Carlo sampling scheme 'Tree-Based Deterministic Sampling
      CNV' (TDSCNV). We compare our method with polyHap(v2.0), the only currently
      available software able to perform inference in CNV/SNP genotypes, on datasets of
      varying number of markers. We have found that both algorithms show similar
      accuracy but TDSCNV is an order of magnitude faster while scaling linearly with
      the number of markers and number of individuals and thus could be the method of
      choice for haplotype inference in such datasets. Our method is implemented in the
      TDSCNV package which is available for download at
      http://www.ee.columbia.edu/~anastas/tdscnv. 

PMID- 24868200
TI  - A novel single neuron perceptron with universal approximation and XOR computation
      properties.
AB  - We propose a biologically motivated brain-inspired single neuron perceptron (SNP)
      with universal approximation and XOR computation properties. This computational
      model extends the input pattern and is based on the excitatory and inhibitory
      learning rules inspired from neural connections in the human brain's nervous
      system. The resulting architecture of SNP can be trained by supervised excitatory
      and inhibitory online learning rules. The main features of proposed single layer
      perceptron are universal approximation property and low computational complexity.
      The method is tested on 6 UCI (University of California, Irvine) pattern
      recognition and classification datasets. Various comparisons with multilayer
      perceptron (MLP) with gradient decent backpropagation (GDBP) learning algorithm
      indicate the superiority of the approach in terms of higher accuracy, lower time,
      and spatial complexity, as well as faster training. Hence, we believe the
      proposed approach can be generally applicable to various problems such as in
      pattern recognition and classification. 

PMID- 24868201
TI  - The prognostic value of lymph nodes dissection number on survival of patients
      with lymph node-negative gastric cancer.
AB  - Objective. The study was designed to explore the prognostic value of examined
      lymph node (LN) number on survival of gastric cancer patients without LN
      metastasis. Methods. Between August 1995 and January 2011, 300 patients who
      underwent gastrectomy with D2 lymphadenectomy for LN-negative gastric cancer were
      reviewed. Patients were assigned to various groups according to LN dissection
      number or tumor invasion depth. Some clinical outcomes, such as overall survival,
      operation time, length of stay, and postoperative complications, were compared
      among all groups. Results. The overall survival time of LN-negative GC patients
      was 50.2 +/- 30.5 months. Multivariate analysis indicated that LN dissection
      number (P < 0.001) and tumor invasion depth (P < 0.001) were independent
      prognostic factors of survival. The number of examined LNs was positively
      correlated with survival time (P < 0.05) in patients with same tumor invasion
      depth but not correlated with T1 stage or examined LNs >30. Besides, it was not
      correlated with operation time, transfusion volume, length of postoperative stay,
      or postoperative complication incidence (P > 0.05). Conclusions. The number of
      examined lymph nodes is an independent prognostic factor of survival for patients
      with lymph node-negative gastric cancer. Sufficient dissection of lymph nodes is
      recommended during surgery for such population. 

PMID- 24868202
TI  - Proanthocyanidin from grape seed extracts protects indomethacin-induced small
      intestinal mucosal injury.
AB  - Proanthocyanidin (grape seed proanthocyanidin extracts, GSPEs) is an antioxidant
      and scavenges free radicals. Excessive oxidative stress and free radical
      production are major components in the pathogenesis of NSAID-induced small
      intestinal injury. We investigated the effect of GSPEs on indomethacin-induced
      intestinal mucosal injury in the rat. Rats were allocated into four groups: the
      null control group, the indomethacin control group, the low-dose GSPEs group, and
      the high-dose GSPEs group. GSPEs were administered for 4 days. Then indomethacin
      and GSPEs were coadministered for the following 2 days by oral route. The dose of
      indomethacin was 200 mg/Kg. The doses of GSPEs were 100 mg/Kg for low-dose group
      and 300 mg/Kg for high-dose group. Luminal bleeding was solely observed in one of
      5 rats from indomethacin control group. The number of ulcer count was reduced to
      0.1 +/- 0.3 per rat in GSPEs treated group compared to 1.4 +/- 0.5 per rat in
      indomethacin control group. Submucosal inflammatory cell infiltration was also
      reduced to 50% in GSPEs treated group. The tissue level of prostaglandin E2 was
      not affected by GSPEs treatment. GSPEs attenuated the indomethacin-induced small
      intestinal injury irrespective of the tissue PGE2 depletion and glutathione
      consumption. 

PMID- 24868203
TI  - Transjugular intrahepatic portosystemic shunt for the treatment of portal
      hypertension in noncirrhotic patients with portal cavernoma.
AB  - Background. The purpose of this study was to evaluate the safety and efficacy of
      transjugular intrahepatic portosystemic shunt (TIPS) placement in the management
      of portal hypertension in noncirrhotic patients with portal cavernoma. Methods.
      We conducted a single institution retrospective analysis of 15 noncirrhotic
      patients with portal cavernoma treated with TIPS placement. 15 patients (4 women
      and 11 men) were evaluated via the technical success of TIPS placement,
      procedural complications, and follow-up shunt patency. Results. TIPS placement
      was technically successful in 11 out of 15 patients (73.3%). Procedure-related
      complications were limited to a single instance of hepatic encephalopathy in one
      patient. In patients with successful shunt placement, the portal pressure
      gradient decreased from 25.8 +/- 5.7 to 9.5 +/- 4.2 mmHg (P < 0.001). TIPS
      dysfunction occurred in two patients during a median follow-up time of 45.2
      months. Revision was not performed in one patient due to inadequate inflow. The
      other patient died of massive gastrointestinal bleeding in a local hospital. The
      remaining nine patients maintained functioning shunts through their last
      evaluation. Conclusions. TIPS is a safe and effective therapeutic treatment for
      noncirrhotic patients with symptomatic portal hypertension secondary to portal
      cavernoma. 

PMID- 24868204
TI  - Cyanoacrylate injection compared with band ligation for acute gastric variceal
      hemorrhage: a meta-analysis of randomized controlled trials and observational
      studies.
AB  - Background. Cyanoacrylate injection (GVO) and band ligation (GVL) are effective
      treatments for gastric variceal hemorrhage. However, data on the optimal
      treatment are still controversial. Methods. For our overall analysis, relevant
      studies were identified from several databases. For each outcome, data were
      pooled using a fixed-effect or random-effects model according to the result of a
      heterogeneity test. Results. Seven studies were included. Compared with GVL, GVO
      was associated with increased likelihood of hemostasis of active bleeding (odds
      ratio [OR] = 2.32; 95% confidence interval [CI] = 1.19-4.51) and a longer gastric
      variceal rebleeding-free period (hazard ratio = 0.37; 95% CI = 0.24-0.56). No
      significant differences were observed between GVL and GVO for mortality (hazard
      ratio = 0.66; 95% CI = 0.43-1.02), likelihood of variceal obliteration (OR =
      0.89; 95% CI = 0.52-1.54), number of treatment sessions required for complete
      variceal eradication (weighted mean difference = -0.45; 95% CI = -1.14-0.23), or
      complications (OR = 1.02; 95% CI = 0.48-2.19). Conclusion. GVO may be superior to
      GVL for achieving hemostasis and preventing recurrence of gastric variceal
      rebleeding but has no advantage over GVL for mortality and complications.
      Additional studies are warranted to enable definitive conclusions. 

PMID- 24868205
TI  - Vitamin D Binding Protein Impact on 25-Hydroxyvitamin D Levels under Different
      Physiologic and Pathologic Conditions.
AB  - There is a high prevalence of vitamin D deficiency worldwide, but how to define
      vitamin D deficiency is controversial. Currently, the plasma concentration of
      total 25-hydroxyvitamin D [25(OH)D] is considered an indicator of vitamin D
      status. The free hormone hypothesis states that protein-bound hormones are
      inactive while unbound hormones are free to exert biological activity. The
      majority of circulating 25(OH)D and 1,25(OH)2D is tightly bound to vitamin D
      binding protein (DBP), 10-15% is bound to albumin, and less than 1% of
      circulating vitamin D exists in an unbound form. While DBP is relatively stable
      in most healthy populations, a recent study showed that there are gene
      polymorphisms associated with race and ethnicity that could alter DBP levels and
      binding affinity. Furthermore, in some clinical situations, total vitamin D
      levels are altered and knowing whether DBP is also altered may have treatment
      implications. The aim of this review is to assess DBP concentration in different
      physiological and pathophysiological conditions. We suggest that DBP should be
      considered in the interpretation of 25(OH)D levels. 

PMID- 24868207
TI  - Preparation of Starch/Gelatin Blend Microparticles by a Water-in-Oil Emulsion
      Method for Controlled Release Drug Delivery.
AB  - Information on the preparation and properties of starch/gelatin blend
      microparticles with and without crosslinking for drug delivery is presented. The
      blend microparticles were prepared by the water-in-oil emulsion solvent diffusion
      method. Glutaraldehyde and methylene blue were used as the crosslinker and the
      water-soluble drug model, respectively. The blend microparticles were
      characterized by scanning electron microscopy (SEM), Fourier transform infrared
      (FTIR) spectroscopy, and UV-Vis spectroscopy. The functional groups of the starch
      and gelatin blend matrices were determined from the FTIR spectra. Blend
      microparticles with a nearly spherical shape and internal porous structure were
      observed from SEM images. The average particle size of the gelatin microparticles
      depended on the crosslinker ratio but not on the starch/gelatin blend ratio. The
      in vitro drug release content significantly decreased as the crosslinker ratio
      increased and the starch blend ratio decreased. The results demonstrated that the
      starch/gelatin blend microparticles should be a useful controlled release
      delivery carrier for water-soluble drugs. 

PMID- 24868206
TI  - Bisphosphonate-related osteonecrosis of the jaw: a review of the literature.
AB  - Bisphosphonates (BPs) are a class of drugs used to treat osteoporosis and
      malignant bone metastasis. BPs show high binding capacity to the bone matrix,
      especially in sites of active bone metabolism. The American Society for Bone and
      Mineral Research defines BRONJ as "an area of exposed bone in the maxillofacial
      region that has not healed within 8 weeks after identification by a healthcare
      provider in a patient who is receiving or has been exposed to a bisphosphonate
      and has not had radiation therapy to the craniofacial region." Bisphosphonate
      related osteonecrosis of the jaw (BRONJ) can adversely affect quality of life, as
      it may produce significant morbidity. The American Association of Oral and
      Maxillofacial Surgeons (AAOMS) considers as vitally important that information on
      BRONJ be disseminated to other dental and medical specialties. The purpose of
      this work is to offer a perspective on how dentists should manage patients on
      BPs, to show the benefits of accurately diagnosing BRONJ, and to present
      diagnostic aids and treatments strategies for the condition. 

PMID- 24868208
TI  - Occult Hepatitis B Virus Infection among HIV Positive Patients in Nigeria.
AB  - HIV has been known to interfere with the natural history of hepatitis B virus
      (HBV) infection. In this study we investigate the prevalence of occult hepatitis
      B virus infection (OBI) among HIV-infected individuals in Nigeria. Overall, 1200
      archived HIV positive samples were screened for detectable HBsAg using rapid
      technique, in Ikole Ekiti Specialist Hospital. The HBsAg negative samples were
      tested for HBsAg, anti-HBc, and anti-HCV by ELISA. Polymerase chain reaction was
      used for HBV DNA amplification and CD4 counts were analyzed by cytometry. Nine
      hundred and eighty of the HIV samples were HBsAg negative. HBV DNA was detected
      in 21/188 (11.2%) of patients without detectable HBsAg. CD4 count for the
      patients ranged from 2 to 2,140 cells/ MU L of blood (mean = 490 cells/ MU L of
      blood). HCV coinfection was detected only in 3/188 (1.6%) of the HIV-infected
      patients (P > 0.05). Twenty-eight (29.2%) of the 96 HIV samples screened were
      positive for anti-HBc. Averagely the HBV viral load was <50 copies/mL in the OBI
      samples examined by quantitative PCR. The prevalence of OBI was significantly
      high among HIV-infected patients. These findings highlight the significance of
      nucleic acid testing in HBV diagnosis in HIV patients. 

PMID- 24868209
TI  - Do maternal quality of life and breastfeeding difficulties influence the
      continuation of exclusive breastfeeding?
AB  - Objectives. This study was conducted to determine whether maternal quality of
      life (QOL) and breastfeeding difficulties influence the continuation of exclusive
      breastfeeding (EBF). Methods. In a survey, 358 consecutive pregnant women filled
      out a quality of life questionnaire in the third trimester of pregnancy and the
      breastfeeding experience scale at 4 weeks postpartum. We assessed breastfeeding
      practices every month up to 6 months postpartum. Results. Only 11.8% of women
      continued EBF at six months. Mothers who continued EBF at 2 and 4 months
      postpartum had better QOL in late pregnancy than mothers who discontinued it (P <
      0.05). There were no significant differences between the two groups in QOL scores
      at 6 months postpartum. Mothers who continued EBF at 2 months postpartum
      experienced less breastfeeding difficultties during one month postpartum than
      mothers who discontinued it (P < 0.05). Conclusion. In attempts to promote EBF,
      mothers with poor QOL or breastfeeding difficulties in early postpartum should be
      identified and helped. 

PMID- 24868210
TI  - Utility of gastric lavage in vigorous neonates delivered with meconium stained
      liquor: a randomized controlled trial.
AB  - Objective. To determine the incidence of feed intolerance in vigorous babies with
      meconium stained liquor (MSL) who received prophylactic gastric lavage as
      compared to those who were not subjected to this procedure. Design. Randomized
      controlled trial. Setting. Tertiary care teaching hospital.
      Participants/Intervention. 330 vigorous babies delivered with MSL and satisfying
      the predefined inclusion criteria were randomized either to receive gastric
      lavage (group A, n = 165) or to not receive gastric lavage (group B, n = 153).
      Clinical monitoring was subsequently performed and recorded in prestructured
      proforma. Results. There was no significant statistical difference (P > 0.05) in
      incidence of feed intolerance in "lavage" and "no lavage" groups. Secondary
      Outcome. There was no evidence of secondary respiratory distress in either group.
      None of the patients in the lavage group exhibited adverse effects owing to the
      procedure. Conclusions. There is no role of prophylactic gastric lavage in
      neonates born with MSL. 

PMID- 24868211
TI  - Critical Analysis of PIM2 Score Applicability in a Tertiary Care PICU in Western
      India.
AB  - Objective. Children have limited physiological reserve that deteriorates rapidly.
      Present study profiled patients admitted to PICU and determined PIM2 score
      applicability in Indian setting. Patients and Methods. Prospective observational
      study. Results. In 742 consecutive admissions, male : female ratio was 1.5 : 1,
      35.6% patients were ventilated, observed mortality was 7%, and 26.4% were <1
      year. The profile included septicemia and septic shock (29.6%), anemia (27.1%),
      pneumonia (19.6%), and meningitis and encephalitis (17.2%). For the first year,
      sensitivity of PIM2 was 65.8% and specificity was 71% for cutoff value at 1.9 by
      ROC curve analysis. The area under the curve was 0.724 (95% CI: 0.69, 0.76). This
      cutoff was validated for second year data yielding similar sensitivity (70.6%)
      and specificity (65%). Logistic regression analysis (LRA) over entire data
      revealed various variables independently associated with mortality along with
      PIM2 score. Another logistic model with same input variables except PIM2 yielded
      the same significant variables with Nagelkerke R square of 0.388 and correct
      classification of 78.5 revealing contribution of PIM2 in predicting mortality is
      meager. Conclusion. Infectious diseases were the commonest cause of PICU
      admission and mortality. PIM2 scoring did not explain the outcome adequately,
      suggesting need for recalibration. Following PALS/GEM guidelines was associated
      with better outcome. 

PMID- 24868214
TI  - The relationship between eosinophilia and bronchopulmonary dysplasia in premature
      infants at less than 34 weeks' gestation.
AB  - PURPOSE: Eosinophilia is common in premature infants, and its incidence increases
      with a shorter gestation period. We investigated the clinical significance of
      eosinophilia in premature infants born at <34 weeks gestation. METHODS: We
      analyzed the medical records of premature infants born at <34 weeks gestation who
      were admitted to the neonatal intensive care unit at Ewha Womans University
      Mokdong Hospital between January 2003 and September 2010. Eosinophilia was
      defined as an eosinophil percentage of >3% of the total leukocytes. Perinatal
      parameters and clinical parameters were also analyzed. RESULTS: Of the 261
      infants born at <34 weeks gestation, 22.4% demonstrated eosinophilia at birth.
      The eosinophil percentage peaked in the fourth postnatal week at 7.5%. The
      incidence of severe eosinophilia increased after birth up to the fourth postnatal
      week when 8.8% of all patients had severe eosinophilia. Severity of eosinophilia
      was positively correlated with a lower gestational age, birth weight, and Apgar
      score. Respiratory distress syndrome, bronchopulmonary dysplasia,
      nephrocalcinosis, intraventricular hemorrhage, and sepsis were associated with a
      higher eosinophil percentage. The eosinophil percentage was significantly higher
      in infants with bronchopulmonary dysplasia from the first postnatal week and the
      percentage was the highest in the fourth postnatal week, with the maximal
      difference being 4.1% (P<0.001). CONCLUSION: Eosinophilia is common in premature
      infants and reaches peak incidence and severity in the fourth postnatal week. The
      eosinophil percentage was significantly higher in bronchopulmonary dysplasia
      patients from the first postnatal week. Severe eosinophilia was significantly
      associated with the incidence of bronchopulmonary dysplasia even after adjusting
      for other variables.

PMID- 24868212
TI  - Genetic risk factors associated with respiratory distress syndrome.
AB  - Respiratory distress syndrome (RDS) among preterm infants is typically due to a
      quantitative deficiency of pulmonary surfactant. Aside from the degree of
      prematurity, diverse environmental and genetic factors can affect the development
      of RDS. The variance of the risk of RDS in various races/ethnicities or
      monozygotic/dizygotic twins has suggested genetic influences on this disorder. So
      far, several specific mutations in genes encoding surfactant-associated molecules
      have confirmed this. Specific genetic variants contributing to the regulation of
      pulmonary development, its structure and function, or the inflammatory response
      could be candidate risk factors for the development of RDS. This review
      summarizes the background that suggests the genetic predisposition of RDS, the
      identified mutations, and candidate genetic polymorphisms of pulmonary surfactant
      proteins associated with RDS. 

PMID- 24868215
TI  - Blood culture contamination in hospitalized pediatric patients: a single
      institution experience.
AB  - PURPOSE: Blood culture is the most important tool for detecting bacteremia in
      children with fever. However, blood culture contamination rates range from 0.6%
      to 6.0% in adults; rates for young children have been considered higher than
      these, although data are limited, especially in Korea. This study determined the
      contamination rate and risk factors in pediatric patients visiting the emergency
      room (ER) or being admitted to the ward. METHODS: We conducted a retrospective
      chart review of blood cultures obtained from children who visited Yonsei
      Severance Hospital, Korea between 2006 and 2010. Positive blood cultures were
      labeled as true bacteremia or contamination according to Centers for Disease
      Control and Prevention/National Healthcare Safety Network definitions for
      laboratory-confirmed bloodstream infection, after exclusion of cultures drawn
      from preexisting central lines only. RESULTS: Among 40,542 blood cultures, 610
      were positive, of which 479 were contaminations and 131 were true bacteremia
      (overall contamination rate, 1.18%). The contamination rate in the ER was
      significantly higher than in the ward (1.32% vs. 0.66%, P<0.001). The rate was
      higher in younger children (2.07%, 0.94%, and 0.61% in children aged <1 year, 1-6
      years, and >6 years, respectively). CONCLUSION: Overall, contamination rates were
      higher in younger children than in older children, given the difficulty of
      performing blood sampling in younger children. The contamination rates from the
      ER were higher than those from the ward, not accounted for only by overcrowding
      and lack of experience among personnel collecting samples. Further study to
      investigate other factors affecting contamination should be required.

PMID- 24868213
TI  - Effectiveness and safety of seasonal influenza vaccination in children with
      underlying respiratory diseases and allergy.
AB  - Influenza causes acute respiratory infections and various complications. Children
      in the high-risk group have higher complication and hospitalization rates than
      high-risk elderly individuals. Influenza prevention in children is important, as
      they can be a source infection spread in their communities. Influenza vaccination
      is strongly recommended for high-risk children with chronic underlying
      circulatory and respiratory disease, immature infants, and children receiving
      long-term immunosuppressant treatment or aspirin. However, vaccination rates in
      these children are low because of concerns regarding the exacerbation of
      underlying diseases and vaccine efficacy. To address these concerns, many
      clinical studies on children with underlying respiratory diseases have been
      conducted since the 1970s. Most of these reported no differences in
      immunogenicity or adverse reactions between healthy children and those with
      underlying respiratory diseases and no adverse effects of the influenza vaccine
      on the disease course. Further to these studies, the inactivated split-virus
      influenza vaccine is recommended for children with underlying respiratory
      disease, in many countries. However, the live-attenuated influenza vaccine (LAIV)
      is not recommended for children younger than 5 years with asthma or recurrent
      wheezing. Influenza vaccination is contraindicated in patients with severe
      allergies to egg, chicken, or feathers, because egg-cultivated influenza vaccines
      may contain ovalbumin. There has been no recent report of serious adverse events
      after influenza vaccination in children with egg allergy. However, many experts
      recommend the trivalent influenza vaccine for patients with severe egg allergy,
      with close observation for 30 minutes after vaccination. LAIV is still not
      recommended for patients with asthma or egg allergy. 

PMID- 24868216
TI  - Predictive value of C-reactive protein in response to macrolides in children with
      macrolide-resistant Mycoplasma pneumoniae pneumonia.
AB  - PURPOSE: The prevalence of macrolide-resistant Mycoplasma pneumoniae (MRMP) has
      increased worldwide. The aim of this study was to estimate the proportion of MRMP
      in a tertiary hospital in Korea, and to find potential laboratory markers that
      could be used to predict the efficacy of macrolides in children with MRMP
      pneumonia. METHODS: A total of 95 patients with M. pneumoniae pneumonia were
      enrolled in this study. Detection of MRMP was based on the results of specific
      point mutations in domain V of the 23S rRNA gene. The medical records of these
      patients were reviewed retrospectively and the clinical course and laboratory
      data were compared. RESULTS: The proportion of patients with MRMP was 51.6% and
      all MRMP isolates had the A2063G point mutation. The MRMP group had longer
      hospital stay and febrile period after initiation of macrolides. The levels of
      serum C-reactive protein (CRP) and interleukin-18 in nasopharyngeal aspirate were
      significantly higher in patients who did not respond to macrolide treatment. CRP
      was the only significant factor in predicting the efficacy of macrolides in
      patients with MRMP pneumonia. The area under the curve for CRP was 0.69 in
      receiver operating characteristic curve analysis, indicating reasonable
      discriminative power, and the optimal cutoff value was 40.7 mg/L. CONCLUSION: The
      proportion of patients with MRMP was high, suggesting that the prevalence of MRMP
      is rising rapidly in Korea. Serum CRP could be a useful marker for predicting the
      efficacy of macrolides and helping clinicians make better clinical decisions in
      children with MRMP pneumonia.

PMID- 24868217
TI  - Baseline heart rate variability in children and adolescents with vasovagal
      syncope.
AB  - PURPOSE: This study aimed to evaluate the autonomic imbalance in syncope by
      comparing the baseline heart rate variability (HRV) between healthy children and
      those with vasovagal syncope. METHODS: To characterize the autonomic profile in
      children experiencing vasovagal syncope, we evaluated the HRV of 23 patients aged
      7-18 years and 20 healthy children. These children were divided into
      preadolescent (<12 years) and adolescent groups. The following time-domain
      indices were calculated: root mean square of the successive differences (RMSSD);
      standard deviation of all average R-R intervals (SDNN); and frequency domain
      indices including high frequency (HF), low frequency (LF), normalized high
      frequency, normalized low frequency, and low frequency to high frequency ratio
      (LF/HF). RESULTS: HRV values were significantly different between healthy
      children and those with syncope. Student t test indicated significantly higher
      SNDD values (60.46 ms vs. 37.42 ms, P=0.003) and RMSSD (57.90 ms vs. 26.92 ms,
      P=0.000) in the patient group than in the control group. In the patient group,
      RMSSD (80.41 ms vs. 45.89 ms, P=0.015) and normalized HF (61.18 ms vs. 43.19 ms,
      P=0.022) were significantly higher in adolescents, whereas normalized LF (38.81
      ms vs. 56.76 ms, P=0.022) and LF/HF ratio (0.76 vs. 1.89, P=0.041) were
      significantly lower in adolescents. In contrast, the control group did not have
      significant differences in HRV values between adolescents and preadolescents.
      CONCLUSION: The results of this study indicated that children with syncope had a
      decreased sympathetic tone and increased vagal tone compared to healthy children.
      Additionally, more severe autonomic imbalances possibly occur in adolescents than
      in preadolescents.

PMID- 24868218
TI  - Percutaneous ultrasound-guided thrombin injection is effective even in infants
      with external iliac artery pseudoaneurysms.
AB  - Iatrogenic pseudoaneurysms are extremely rare in children. Conventional
      management of pseudoaneurysms in adults has included surgical repair, ultrasound
      guided compression, and more recently, endovascular embolization. However, in
      infants and children, there is little information regarding the applicability of
      such treatment modalities, which have been effective in adults, because of its
      rarity. Here, we present the case of a 6-month-old infant who developed a
      postprocedural pseudoaneurysm of the external iliac artery, which was
      successfully treated with ultrasound-guided percutaneous thrombin injection. 

PMID- 24868219
TI  - Pulmonary hemorrhage in pediatric lupus anticoagulant hypoprothrombinemia
      syndrome.
AB  - Lupus anticoagulant-hypoprothrombinemia syndrome (LAHPS), a very rare disease
      that is caused by the presence of antifactor II antibodies, is usually
      counterbalanced by the prothrombotic effect of lupus anticoagulant (LAC).
      Patients with LAHPS are treated using fresh frozen plasma, steroids,
      immunosuppressive agents, and immunoglobulins for managing the disease and
      controlling hemorrhages. Notably, steroids are the important treatment for
      treating hypoprothrombinemia and controlling the bleeding. However, some patients
      suffer from severe, life-threatening hemorrhages, when factor II levels remain
      very low in spite of treatment with steroids. Here, we report a case of LAHPS in
      a 15-year-old girl who experienced pulmonary hemorrhage with rapid progression.
      She was referred to our hospital owing to easy bruising and prolonged bleeding.
      She was diagnosed with LAHPS that presented with pancytopenia, positive
      antinuclear antibody, proloned prothrombin time, activated partial thromboplastin
      time, positive LAC antibody, and factor II deficiency. Her treatment included
      massive blood transfusion, high-dose methylprednisolone, vitamin K, and
      immunoglobulin. However, she died due to uncontrolled pulmonary hemorrhage. 

PMID- 24868220
TI  - Current concepts in primary effusion lymphoma and other effusion-based lymphomas.
AB  - Primary effusion lymphoma (PEL) is a human herpes virus 8 (HHV8)-positive large B
      cell neoplasm that presents as an effusion with no detectable tumor in
      individuals with human immunodeficiency virus infection or other immune
      deficiencies. PEL is an aggressive neoplasm with a poor prognosis. PEL cells show
      diverse morphologies, ranging from immunoblastic or plasmablastic to anaplastic.
      The immunophenotype of PEL is distinct, but its lineage can be misdiagnosed if
      not assessed thoroughly. PEL cells usually express CD45, lack B- and T-cell
      associated antigens, and characteristically express lymphocyte activation
      antigens and plasma cell-associated antigens. Diagnosis of PEL often requires the
      demonstration of a B-cell genotype. HHV8 must be detected in cells to diagnose
      PEL. In most cases, PEL cells also harbor the Epstein-Barr virus (EBV) genome.
      Similar conditions associated with HHV8 but not effusion-based are called
      "extracavitary PELs." PELs should be differentiated from HHV8-negative, EBV
      positive, body cavity-based lymphomas in patients with long-standing chronic
      inflammation; the latter can occur in tuberculous pleuritis, artificial
      pneumothorax, chronic liver disease and various other conditions. Despite their
      morphological similarity, these various lymphomas require different therapeutic
      strategies and have different prognostic implications. Correct diagnosis is
      essential to manage and predict the outcome of patients with PEL and related
      disorders. 

PMID- 24868221
TI  - Pleural mesothelioma: an institutional experience of 66 cases.
AB  - BACKGROUND: Malignant mesothelioma of the pleura is an aggressive tumor known to
      be associated with asbestos. Histological diagnosis of mesothelioma is
      challenging and is usually aided by immunohistochemical markers. METHODS: During
      an 18-year period (1995-2012), 66 patients with pleural mesothelioma were
      diagnosed at the Samsung Medical Center in Seoul. We reviewed hematoxylin and
      eosin and immunohistochemical slides of pleural mesothelioma and evaluated their
      pathological and clinical features. RESULTS: The male-to-female ratio was 1.75:1,
      and age of patients ranged from 28 to 80 years with an average age of 56.84
      years. Twenty-two out of 66 patients underwent curative pneumonectomy. Follow-up
      data was available in 60 patients (90.9%), and 50 of them (83.3%) died from the
      disease. The average overall survival was 15.39 months. Histologically, the
      epithelioid type was the most common, followed by the sarcomatoid and the
      biphasic types. Epidemiologic information was not available in most cases, and
      only one patient was confirmed to have a history of asbestos exposure.
      CONCLUSIONS: Malignant mesothelioma of the pleura is a fatal tumor, and the
      therapeutic benefit of pneumonectomy remains unproven. The combination of
      calretinin, Wilms tumor 1, HMBE-1, and thyroid transcription factor-1 may provide
      high diagnostic accuracy in diagnosing mesothelioma.

PMID- 24868222
TI  - KRAS Mutation Detection in Non-small Cell Lung Cancer Using a Peptide Nucleic
      Acid-Mediated Polymerase Chain Reaction Clamping Method and Comparative
      Validation with Next-Generation Sequencing.
AB  - BACKGROUND: KRAS is one of commonly mutated genetic "drivers" in non-small cell
      lung cancers (NSCLCs). Recent studies indicate that patients with KRAS-mutated
      tumors do not benefit from adjuvant chemotherapy, so there is now a focus on
      targeting KRAS-mutated NSCLCs. A feasible mutation detection method is required
      in order to accurately test for KRAS status. METHODS: We compared direct Sanger
      sequencing and the peptide nucleic acid (PNA)-mediated polymerase chain reaction
      (PCR) clamping method in 134 NSCLCs and explored associations with
      clinicopathological factors. Next-generation sequencing (NGS) was used to
      validate the results of discordant cases. To increase the resolution of low-level
      somatic mutant molecules, PNA-mediated PCR clamping was used for mutant
      enrichment prior to NGS. RESULTS: Twenty-one (15.7%) cases were found to have the
      KRAS mutations using direct sequencing, with two additional cases by the PNA
      mediated PCR clamping method. The frequencies of KRAS mutant alleles were 2% and
      4%, respectively, using conventional NGS, increasing up to 90% and 89%, using
      mutant-enriched NGS. The KRAS mutation occurs more frequently in the tumors of
      smokers (p=.012) and in stage IV tumors (p=.032). CONCLUSIONS: Direct sequencing
      can accurately detect mutations, but, it is not always possible to obtain a tumor
      sample with sufficient volume. The PNA-mediated PCR clamping can rapidly provide
      results with sufficient sensitivity.

PMID- 24868223
TI  - IMP3, a Promising Prognostic Marker in Clear Cell Renal Cell Carcinoma.
AB  - BACKGROUND: Insulin-like growth factor II mRNA-binding protein 3 (IMP3) has been
      reported as a prognostic biomarker in various cancers. To validate IMP3 as a
      prognostic biomarker in renal cell carcinoma (RCC), we investigated the
      expression of IMP3, p53, and Ki-67, and their associations with clinicopathologic
      outcomes. METHODS: We studied 148 clear cell RCCs (CCRCCs) from patients who
      underwent radical nephrectomy. The expression levels of IMP3, p53, and Ki-67 were
      assessed by immunohistochemical staining and the clinical and pathologic
      parameters were retrospectively reviewed. RESULTS: Twenty-nine percent of CCRCCs
      expressed IMP3. Forty-one percent of IMP3-immunopositive tumors developed
      metastases, while only 11.4% of IMP3-negative tumors developed metastases
      (p<.001). A Kaplan-Meier curve showed that patients with IMP3-immunopositive
      tumors had lower metastasis-free survival and cancer-specific survival than did
      those with IMP3-immunonegative tumors (p<.001 and p<.001, respectively).
      Expression of high Ki-67 proliferation index was also associated with a higher
      metastatic rate. In the multivariate Cox regression analysis, pT stage and IMP3
      positivity were independently associated with disease-specific survival.
      CONCLUSIONS: IMP3 is an independent prognostic biomarker for patients with CCRCC
      to predict metastasis and poor outcome.

PMID- 24868224
TI  - Tumor sprouting in papillary thyroid carcinoma is correlated with lymph node
      metastasis and recurrence.
AB  - BACKGROUND: Identification of poor prognostic factors in papillary thyroid
      carcinoma (PTC) patients is important for the patients' care and follow-up. We
      can sometimes see small tumor clusters without desmoplasia and no evidence of
      lymphatic emboli around the main tumor mass of PTC. We termed this form of tumor
      clustering, 'tumor sprouting,' and determined whether these tumors correlate with
      lymphovascular invasion, lymph node metastasis, and recurrence. METHODS: We
      analyzed a total of 204 cases of papillary thyroid macrocarcinoma. Number, size
      and distance from the main tumor of the tumor sprouting were observed and
      analyzed with clinicopathologic characteristics. RESULTS: Tumor sprouting was
      observed in 101 patients. Presence of tumor sprouting was significantly
      associated with positive resection margin (p=.002), lymphovascular invasion
      (p=.001), lymph node metastasis (p<.001), and recurrence (p=.004). Univariate
      analysis of recurrence-free survival revealed that tumor multiplicity (p=.037),
      positive resection margin (p=.007), lymphovascular invasion (p=.004), lymph node
      metastasis (p<.001), and tumor sprouting (p=.004) were poor prognostic factors.
      In multivariate analysis, positive resection margin was an independent poor
      prognostic factor of recurrence. CONCLUSIONS: In conclusion, tumor sprouting is
      significantly correlated with lymph node metastasis and recurrence. Evaluation of
      tumor sprouting in PTC patients could be helpful in predicting tumor recurrence
      or lymph node metastasis.

PMID- 24868225
TI  - Characteristics of Cutaneous Lymphomas in Korea According to the New WHO-EORTC
      Classification: Report of a Nationwide Study.
AB  - BACKGROUND: Previously, cutaneous lymphomas were classified according to either
      the European Organization for the Research and Treatment of Cancer (EORTC) or the
      World Health Organization (WHO) classification paradigms. The aim of this study
      was to determine the relative frequency of Korean cutaneous lymphoma according to
      the new WHO-EORTC classification system. METHODS: A total of 517 patients were
      recruited during a recent 5 year-period (2006-2010) from 21 institutes and
      classified according to the WHO-EORTC criteria. RESULTS: The patients included
      298 males and 219 females, and the mean age at diagnosis was 49 years. The
      lesions preferentially affected the trunk area (40.2%). The most frequent
      subtypes in order of decreasing prevalence were mycosis fungoides (22.2%),
      peripheral T-cell lymphoma (17.2%), CD30+ T-cell lymphoproliferative disorder
      (13.7%), and extranodal natural killer/T (NK/T) cell lymphoma, nasal type
      (12.0%). Diffuse large B-cell lymphoma accounted for 11.2% of cases, half of
      which were secondary cutaneous involvement; other types of B-cell lymphoma
      accounted for less than 1% of cases. CONCLUSIONS: In comparison with data from
      Western countries, this study revealed relatively lower rates of mycosis
      fungoides and B-cell lymphoma in Korean patients, as well as higher rates of
      subcutaneous panniculitis-like T-cell lymphoma and NK/T cell lymphoma.

PMID- 24868226
TI  - Incidence and malignancy rates of diagnoses in the bethesda system for reporting
      thyroid aspiration cytology: an institutional experience.
AB  - BACKGROUND: The Bethesda System for Reporting Thyroid Cytopathology (BSRTC) uses
      six diagnostic categories to standardize communication of thyroid fine-needle
      aspiration (FNA) interpretations between clinicians and cytopathologists. Since
      several studies have questioned the diagnostic accuracy of this system, we
      examined its accuracy in our hospital. METHODS: We calculated the incidences and
      malignancy rates of each diagnostic category in the BSRTC for 1,730 FNAs that
      were interpreted by four cytopathologists in Gangnam Severance Hospital between
      October 1, 2011, and December 31, 2011. RESULTS: The diagnostic incidences of
      categories I-VI were as follows: 13.3%, 40.6%, 9.1%, 0.4%, 19.3%, and 17.3%,
      respectively. Similarly, the malignancy rates of these categories were as
      follows: 35.3%, 5.6%, 69.0%, 50.0%, 98.7%, and 98.9%, respectively. In categories
      II, V, and VI, there were no statistically significant differences in the ranges
      of the malignancy rates among the four cytopathologists. However, there were
      significant differences in the ranges for categories I and III. CONCLUSIONS: Our
      findings suggest that institutions that use the BSRTC should regularly update
      their diagnostic criteria. We also propose that institutions issue an annual
      report of incidences and malignancy rates to help other clinicians improve the
      case management of patients with thyroid nodules.

PMID- 24868227
TI  - Follicular Dendritic Cell Sarcoma of the Inflammatory Pseudotumor-like Variant
      Presenting as a Colonic Polyp.
AB  - Follicular dendritic cell (FDC) sarcoma is rare and is classified either as
      conventional type or inflammatory pseudotumor (IPT)-like variant. Extranodal
      presentation is uncommon and nearly all gastrointestinal FDC tumors are of the
      conventional type. IPT-like variant tumors occur almost exclusively in the liver
      and spleen and are consistently associated with Epstein-Barr virus (EBV). Here we
      report the case of a 78-year-old woman with an IPT-like FDC sarcoma presenting as
      a pedunculated colonic polyp. Histologically, scanty atypical ovoid to spindle
      cells were mixed with a background of florid lymphoplasmacytic infiltrate, which
      led to an initial misdiagnosis of pseudolymphoma. These atypical cells expressed
      CD21, CD23, CD35, and D2-40, and were positive for EBV by in situ hybridization,
      confirming the diagnosis. The patient was free of disease five months after
      polypectomy without adjuvant therapy. Although extremely rare, the differential
      diagnosis for colonic polyp should include FDC sarcoma to avoid an erroneous
      diagnosis. A review of the 24 cases of IPT-like FDC sarcoma reported in the
      literature reveal that this tumor occurs predominantly in females with a
      predilection for liver and spleen, and has a strong association with EBV. 

PMID- 24868228
TI  - Multifocal osteosarcoma of the skull: multiple primary or metastatic? A case
      report.
AB  - Osteosarcoma of the skull is a very rare condition. Moreover, it is extremely
      rare for osteosarcoma to present as multiple lesions confined to the skull. A 58
      year-old woman was admitted with two masses in the parietal area of the skull,
      accompanied by mild headache and tenderness. Imaging revealed two masses with a
      heterogeneous consistency in the cranial bones. Excision craniectomy was
      performed and the pathology was consistent with osteoblastic osteosarcoma. Two
      nodules in the heart were found on routine follow-up imaging while the patient
      was undergoing chemotherapy. The nodules were biopsied and found to be metastatic
      osteosarcoma. 

PMID- 24868229
TI  - Different Protein Expressions between Peripheral Ameloblastoma and Oral Basal
      Cell Carcinoma Occurred at the Same Mandibular Molar Area.
AB  - Peripheral ameloblastoma (PA) in gingiva is rare and often confused with oral
      basal cell carcinoma (OBCC). The tissues of one case of PA and one case of OBCC
      with the same mandibular molar area affected were compared via an
      immunohistochemical examination using 50 antisera. The PA and OBCC showed similar
      proliferation of basaloid epithelial strands, but toluidine blue staining
      revealed that the PA had pinkish juxta-epithelial myxoid tissue, whereas the OBCC
      was infiltrated by many mast cells. Immunohistochemical comparisons showed that
      the PA was strongly positive for ameloblastin, KL1, p63, carcinoembryonic
      antigen, focal adhesion kinase, and cathepsin K, and slightly positive for
      amelogenin, Krox-25, E-cadherin, and PTCH1, whereas the OBCC was not. On the
      other hand, the OBCC was strongly positive for EpCam, matrix metalloprotease
      (MMP)-1, alpha1-antitrypsin, cytokeratin-7, p53, survivin, pAKT1, transforming
      growth factor-beta1, NRAS, TGase-1, and tumor nescrosis factor-alpha, and
      consistently positive for beta-catenin, MMP-2, cathepsin G, TGase-2, SOS-1, sonic
      hedgehog, and the beta-defensins-1, -2, -3, while the PA was not. These data
      suggest that the tumorigeneses of PA and OBCC differ, and that PAs undergo
      odontogenic differentiation and generate oncogenic signals for infiltrative
      growth and bone resorption, whereas OBCCs undergo basaloid epidermal
      differentiation as a result of growth factor/cytokine-related oncogenic signals. 

PMID- 24868230
TI  - Adenocarcinoma arising in gastric duplication cyst.

PMID- 24868231
TI  - Esophageal squamous cell carcinoma in situ overlying leiomyoma mimicking invasive
      cancer: a brief case report.

PMID- 24868232
TI  - Simultaneous Occurrence of Ductal Carcinoma In Situ within Juvenile Fibroadenoma
      in Both Breasts: A Brief Case Report.

PMID- 24868233
TI  - An unusual case of pulmonary mucous gland adenoma with fibromyxoid stroma and
      cartilage islands in 68-year-old woman.

PMID- 24868234
TI  - Fine Needle Aspiration Cytology of Warthin-like Papillary Thyroid Carcinoma: A
      Brief Case Report.

PMID- 24868235
TI  - Complementary and alternative medicine for the treatment of central nervous
      system disorders.

PMID- 24868236
TI  - The effects of wenxin keli on left ventricular ejection fraction and brain
      natriuretic Peptide in patients with heart failure: a meta-analysis of randomized
      controlled trials.
AB  - Objective. To evaluate the beneficial and adverse effects of Wenxin Keli (WXKL),
      either alone or in combination with Western medicine, on the left ventricular
      ejection fraction (LVEF) and plasma brain natriuretic peptide (BNP) in the
      treatment of heart failure (HF). Methods. Seven major electronic databases were
      searched to retrieve potential randomized controlled trials (RCTs) designed to
      evaluate the clinical effectiveness of WXKL, either alone or in combination with
      Western medicine, for HF, with the LVEF or BNP after eight weeks of treatment as
      main outcome measures. The methodological quality of the included studies was
      assessed using criteria from the Cochrane Handbook for Systematic Review of
      Interventions, Version 5.1.0, and analyzed using RevMan 5.1.0 software. Results.
      Eleven RCTs of WXKL were included. The methodological quality of the trials was
      generally evaluated as low. The risk of bias was high. The results of the meta
      analysis showed that WXKL, either alone or in combination with Western medicine,
      was more effective in LVEF and BNP, compared with no medicine or Western medicine
      alone, in patients with HF or HF complicated by other diseases. Five of the
      trials reported adverse events, while the others did not mention them, indicating
      that the safety of WXKL remains uncertain. Conclusions. WXKL, either alone or in
      combination with Western medicine, appears to be more effective in improving the
      LVEF and BNP in patients with HF and HF complications. 

PMID- 24868237
TI  - Color distribution differences in the tongue in sleep disorder.
AB  - Introduction. According to traditional East Asian medicine (TEAM) theory, the
      tongue represents conditions of qi and blood. In the present study, the
      relationship between the tongue and the qi and blood in conditions with no
      apparent disease was investigated. Methods. A total of 454 elderly people with no
      apparent disease were recruited. Two Korean oriental medicine doctors classified
      subjects into a normal group (n = 402) and a sleep disorder group (n = 52). Three
      to five weeks after the experiment, 153 subjects were rerecruited for a second
      experiment. Two-dimensional color histograms, whose seven variables represent the
      color distribution in Commission Internationale de l'Eclairage 1976 (L*, a*, b*)
      color space, were produced from tongue images. Results. The color of the tongue
      body in the sleep disorder group appeared paler than that in the normal group,
      and the tongue coating in the normal group was less widely distributed compared
      with that in the sleep disorder group. The differences in tongue color between
      the normal at first experiment and sleep disorder at second experiment conditions
      were similar to the differences between the normal and the sleep disorder groups.
      Conclusions. The tongue states in the sleep disorder group indicate a qi and
      blood deficiency according to TEAM theory. 

PMID- 24868238
TI  - Traditional medicine in a global environment.

PMID- 24868239
TI  - Potential Protein Phosphatase 2A Agents from Traditional Chinese Medicine against
      Cancer.
AB  - Protein phosphatase 2A (PP2A) is an important phosphatase which regulates various
      cellular processes, such as protein synthesis, cell growth, cellular signaling,
      apoptosis, metabolism, and stress responses. It is a holoenzyme composed of the
      structural A and catalytic C subunits and a regulatory B subunit. As an
      environmental toxin, okadaic acid, is a tumor promoter and binds to PP2A
      catalytic C subunit and the cancer-associated mutations in PP2A structural A
      subunit in human tumor tissue; PP2A may have tumor-suppressing function. It is a
      potential drug target in the treatment of cancer. In this study, we screen the
      TCM compounds in TCM Database@Taiwan to investigate the potent lead compounds as
      PP2A agent. The results of docking simulation are optimized under dynamic
      conditions by MD simulations after virtual screening to validate the stability of
      H-bonds between PP2A- alpha protein and each ligand. The top TCM candidates,
      trichosanatine and squamosamide, have potential binding affinities and
      interactions with key residues Arg89 and Arg214 in the docking simulation. In
      addition, these interactions were stable under dynamic conditions. Hence, we
      propose the TCM compounds, trichosanatine and squamosamide, as potential
      candidates as lead compounds for further study in drug development process with
      the PP2A- alpha protein. 

PMID- 24868240
TI  - The analysis of surface EMG signals with the wavelet-based correlation dimension
      method.
AB  - Many attempts have been made to effectively improve a prosthetic system
      controlled by the classification of surface electromyographic (SEMG) signals.
      Recently, the development of methodologies to extract the effective features
      still remains a primary challenge. Previous studies have demonstrated that the
      SEMG signals have nonlinear characteristics. In this study, by combining the
      nonlinear time series analysis and the time-frequency domain methods, we proposed
      the wavelet-based correlation dimension method to extract the effective features
      of SEMG signals. The SEMG signals were firstly analyzed by the wavelet transform
      and the correlation dimension was calculated to obtain the features of the SEMG
      signals. Then, these features were used as the input vectors of a Gustafson
      Kessel clustering classifier to discriminate four types of forearm movements. Our
      results showed that there are four separate clusters corresponding to different
      forearm movements at the third resolution level and the resulting classification
      accuracy was 100%, when two channels of SEMG signals were used. This indicates
      that the proposed approach can provide important insight into the nonlinear
      characteristics and the time-frequency domain features of SEMG signals and is
      suitable for classifying different types of forearm movements. By comparing with
      other existing methods, the proposed method exhibited more robustness and higher
      classification accuracy. 

PMID- 24868243
TI  - International Women's Day 2014: women's health equity is progress for all.

PMID- 24868242
TI  - Identification of alternative topological domains in chromatin.
AB  - Chromosome conformation capture experiments have led to the discovery of dense,
      contiguous, megabase-sized topological domains that are similar across cell types
      and conserved across species. These domains are strongly correlated with a number
      of chromatin markers and have since been included in a number of analyses.
      However, functionally-relevant domains may exist at multiple length scales. We
      introduce a new and efficient algorithm that is able to capture persistent
      domains across various resolutions by adjusting a single scale parameter. The
      ensemble of domains we identify allows us to quantify the degree to which the
      domain structure is hierarchical as opposed to overlapping, and our analysis
      reveals a pronounced hierarchical structure in which larger stable domains tend
      to completely contain smaller domains. The identified novel domains are
      substantially different from domains reported previously and are highly enriched
      for insulating factor CTCF binding and histone marks at the boundaries. 

PMID- 24868241
TI  - Sparse-view ultrasound diffraction tomography using compressed sensing with
      nonuniform FFT.
AB  - Accurate reconstruction of the object from sparse-view sampling data is an
      appealing issue for ultrasound diffraction tomography (UDT). In this paper, we
      present a reconstruction method based on compressed sensing framework for sparse
      view UDT. Due to the piecewise uniform characteristics of anatomy structures, the
      total variation is introduced into the cost function to find a more faithful
      sparse representation of the object. The inverse problem of UDT is iteratively
      resolved by conjugate gradient with nonuniform fast Fourier transform. Simulation
      results show the effectiveness of the proposed method that the main
      characteristics of the object can be properly presented with only 16 views.
      Compared to interpolation and multiband method, the proposed method can provide
      higher resolution and lower artifacts with the same view number. The robustness
      to noise and the computation complexity are also discussed. 

PMID- 24868244
TI  - Working after cancer diagnosis: should I? shouldn't I?

PMID- 24868245
TI  - International Clinical Trials Day 2014-ancient and modern needs.

PMID- 24868247
TI  - Involvement and continuity in "Initiation, Evolution, Excellency".

PMID- 24868248
TI  - Primary total knee arthroplasty in severe valgus knee.
AB  - AIM: Outcome of primary total arthroplasty for osteoarthritis of the knee with
      valgus deformity. MATERIALS AND METHODS: Between 2005 and 2007, 28 primary total
      knee replacements were performed for osteoarthritis of the knee with valgus
      deformity. 21 cases were women and 7 men with a mean age of 66.6 years (extremes
      54-81). The clinical and radiological evaluations were done considering the knee
      range of motion, Knee Society Score (KSS) and femorotibial angle measured on the
      frontal standing long leg X-rays. Preoperatively, the knee valgus deformity angle
      was 6 to 15 degrees in 14 cases, 15 to 25 degrees in 10 cases and over 25 degrees
      in 4 cases. RESULTS: After a mean follow-up time of 14 months (extremes 7-29),
      the knee range of motion improved from a mean of 71 degrees (extremes 52-87)
      preoperatively to a mean of 95 degrees (extremes 78-110) postoperatively. The KSS
      value improved from 21.3 points (extremes 1-33) preoperatively to 80.7 points
      (extremes 70-92) postoperatively and the frontal femorotibial angle from a mean
      value of 21 degrees (extremes 11-39) of valgus before surgery, to a mean of 9
      degrees (extremes 0-12) of valgus after surgery. CONCLUSIONS: Long leg AP view X
      ray examination in standing position is mandatory. The standard medial
      parapatellar approach is appropriate in this type of arthroplasty even if
      significant knee valgus deviations are present because it avoids the lateral
      approach complications. Postoperatively, one can get an aligned and stable knee
      if a judicious and progressive periarticular soft tissues balancing is achieved,
      in both flexion and extension position.

PMID- 24868249
TI  - Intraoperative cholangiography still a current investigation.
AB  - Laparoscopic cholecystectomy is the standard treatment for patients requiring
      gallbladder removal. Although the advantages of the laparoscopic technique are
      widely accepted, the introduction of this technique has doubled the rate of
      iatrogenic lesions of extrahepatic bile ducts. Research methods for biliary tree
      also evolved, but intraoperative cholangiography, the traditional exploring
      method used for the biliary tree in classic cholecystectomy remains a valuable
      investigation in the laparoscopic technique. We performed a retrospective study
      on a group of patients who underwent cholecystectomy (laparoscopic or classic).
      Of these, intraoperative cholangiography was performed on a total of 108
      patients. Patients who underwent cholangiography motivated by preoperative
      investigations were excluded from the group and the study operates on patients in
      whom the decision to perform cholangiography was taken during surgery (45 cases).
      We have analyzed the criteria that led to the motivation investigation (dilated
      cystic duct, suspected biliary duct stones, suspicion of iatrogenic biliary
      injury) results and subsequent therapeutic conduct. The results showed that in
      90% of the patients, the suspected diagnosis was confirmed by cholangiography (10
      cases with normal cholangiography aspect, oddita 9 cases, 11 cases with bile duct
      stones, 2 cases with biliary tumor and 13 cases of iatrogenic biliary injury). In
      conclusion, the decision to perform intraoperative cholangiography proved
      salutary, the suspected diagnosis was confirmed and the course of treatment was
      adjusted accordingly. 

PMID- 24868246
TI  - Supervised extensions of chemography approaches: case studies of chemical
      liabilities assessment.
AB  - Chemical liabilities, such as adverse effects and toxicity, play a significant
      role in modern drug discovery process. In silico assessment of chemical
      liabilities is an important step aimed to reduce costs and animal testing by
      complementing or replacing in vitro and in vivo experiments. Herein, we propose
      an approach combining several classification and chemography methods to be able
      to predict chemical liabilities and to interpret obtained results in the context
      of impact of structural changes of compounds on their pharmacological profile. To
      our knowledge for the first time, the supervised extension of Generative
      Topographic Mapping is proposed as an effective new chemography method. New
      approach for mapping new data using supervised Isomap without re-building models
      from the scratch has been proposed. Two approaches for estimation of model's
      applicability domain are used in our study to our knowledge for the first time in
      chemoinformatics. The structural alerts responsible for the negative
      characteristics of pharmacological profile of chemical compounds has been found
      as a result of model interpretation. 

PMID- 24868250
TI  - Genetic and epigenetic alterations in differentiated thyroid carcinoma.
AB  - Differentiated thyroid carcinoma (DTC) has a favorable prognosis, but it is
      important to identify those patients who have a high risk of progressive disease
      and DTC-related death at the time of diagnosis. Analyzing genetic and epigenetic
      alterations in thyroid cancer may play a role in tumor diagnosis, prognostic and
      therapeutic strategies. 

PMID- 24868252
TI  - Local drug delivery agents as adjuncts to endodontic and periodontal therapy.
AB  - In the treatment of intracanal and periodontal infections, the local application
      of antibiotics and other therapeutic agents in the root canal or in periodontal
      pockets may be a promising approach to achieve sustained/controlled drug release,
      high antimicrobial activity and low systemic side effects. The conventional
      method for the elimination of subgingival microbial infection includes mechanical
      debridement, irrigation with antimicrobial agents or surgical access. But, the
      effectiveness of conventional nonsurgical treatment is limited by lack of
      accessibility to bacteria in deeper periodontal pockets, and/or does not
      completely eliminate intracanal microorganisms. Surgical intervention may be
      beneficial but cannot be done in all cases, medically compromised cases and also
      in patients not willing to be subjected to surgical therapy. Development of local
      drug delivery systems provides an answer to all such difficulties. This
      comprehensive review tries to cover the detailed information about the latest
      advances in the various local drug delivery systems, their indications,
      contraindications and their advantages over systemic drug therapy. 

PMID- 24868251
TI  - Physiopathological aspects of the subclinical alterations of thyroid function
      associated with acute coronary syndromes.
AB  - The subclinical modification of thyroid function represents an important risk
      factor for the development of acute coronary syndromes, neglected up to this day.
      Knowledge of the physiopathological processes implicated in the alteration of
      thyroid function that induces cardiovascular dysfunction is a necessity for the
      understanding of the phenomena and for the finding of the adequate therapeutic
      solutions. While recognizing the thyroid dysfunction as a modifiable risk factor
      for the acute coronary syndrome, we encountered a new challenge for the clinical
      research regarding its implications. The ability to manage the altered thyroid
      homeostasis may represent a new stage of prevention at a population level for the
      reduction of the cardiac risk, a stage which implies a risk factor that may
      remain clinically mute for a long period of time if left undiagnosed, however
      influencing the development of the acute coronary syndromes. 

PMID- 24868253
TI  - Colic anastomotic leakage risk factors.
AB  - BACKGROUND: Anastomotic leakage is a dreaded complication of colorectal surgery,
      as it greatly increases the morbidity, mortality and has been associated with
      augmented local recurrence and diminished survival. The frequency of this
      complication is high in emergency colorectal surgery, especially for bowel
      occlusion, (13% for emergency vs. 4% in elective), due to visceral distension
      and, therefore, an incongruence in the size of each of the stumps, combined with
      the lack of mechanical preparation and risk of fecal contamination during
      operation. METHODS: We studied the incidence of anastomotic fistula in the
      surgery clinic of the "Sf. Pantelimon" Emergency Hospital, between 2006 and 2010,
      on a lot of 251 patients who underwent different types of colic resection. Apart
      from the anatomic location of the disease, and the level of anastomosis, we
      included in our database the following criteria: the patient's age and gender,
      type of colic pathology, surgical technique, emergency or elective surgery,
      comorbidities. RESULTS: An ileocolic anastomosis was performed for 84 patients
      (33,46 %), for 114 patients (45,41%) a colo-colic anastomosis was carried out, 2
      patients (0,79%) had ileorectal anastomosis and 51 patients (20,31%) underwent a
      colorectal anastomosis. From the comparative analysis of risk factors (the
      emergency interventions, the anastomosis location, the age and gender of the
      patient), a significantly increased value of the relative risk of anastomotic
      fistula was registered for the cases with emergency intervention (x 6,61) and for
      the colorectal anastomosis following the left hemi colectomies (x 2,23).
      DISCUSSIONS: In our study, among the clinical and biological factors analyzed,
      emergency intervention was the most significant factor associated with
      anastomotic leakage. Surgery performed in emergency settings, on debilitated
      patients without adequate preoperative preparation, has an increased risk for
      anastomotic dehiscence.

PMID- 24868254
TI  - Proinsulin and age in general population.
AB  - OBJECTIVE: The objective of this study was to assess the relationship between
      fasting proinsulin (PI) and age in general population and to determine whether
      there are differences regarding this association in obese and non-obese persons.
      METHODS: A random population-based sample (n=656) of Romanians (26-80 years)
      living in Bucharest, Romania was studied; 432 persons had diabetes and they were
      not analyzed in this paper. Circulating levels of fasting plasma glucose (FPG),
      fasting plasma insulin (FPI), fasting plasma proinsulin (FPP), fasting plasma C
      peptide, HbA1c, lipid profile, creatinine, urea were measured. The homeostasis
      model assessment of insulin resistance (HOMA-IR), HOMA-B, and Quicki index were
      also calculated. RESULTS: For all participants proinsulin was the highest in the
      third quartile of the age group (59-67 years), with a median proinsulin of 5.8
      pmol/L. Subsequently, proinsulin increased with age, from 2.6 pmol/L for
      participants aged 20-51 years, to 4.7 pmol/L for participants aged 51-59 years;
      proinsulin levels decreased in the upper quartile 4.8 pmol/L for those aged over
      67 years. In sex-specific analyses, proinsulin increased with age for both men
      and women, except for those in the upper quartile. The prevalence of the obesity
      was 30.4% (n=68); obesity prevalence did not increase with age (p=0.26). Fasting
      proinsulin levels significantly increased with body mass index (BMI) category
      from lean (n=67, 2.9 pmol/L) to overweight (n=89, 4.5 pmol/L) and obese (n=69,
      6.63 pmol/L) (p<0.0001). CONCLUSIONS: Our study has demonstrated a close
      association between age and elevated proinsulin and proinsulin/insulin ratio in
      general population.

PMID- 24868255
TI  - Fat graft, laser CO2 and platelet-rich-plasma synergy in scars treatment.
AB  - RATIONALE: Many treatments have been proposed for cosmetic or functional
      improvement of scars. It is known that fat grafts and laser treatment can have
      beneficial effects on the remodeling of scar tissue, and platelet-rich plasma
      (PRP) can be effective during the wound-healing process. We hypothesized that
      laser and PRP can enhance fat graft survival and the combination would be
      effective in improving scars appearance. OBJECTIVE: The purpose of this study was
      to evaluate the efficacy of these combinations in the treatment of atrophic and
      contractile scars. METHODS AND RESULTS: From 2008-2013, we treated with this
      combination 64 patients affected by atrophic and contractile scars involving
      different body parts. At 6 months the patients' overall satisfaction rate was
      excellent for over 50% of the patients. DISCUSSION: The association of an
      ablative laser CO2 with PRP and autologous fat graft seems to be a promising and
      effective therapeutic approach for atrophic and contractile scars. ABBREVIATIONS:
      PRP platelet-rich plasma, OTI orotracheal intubation, HLLT high level laser
      therapy, LLLT low level laser therapy.

PMID- 24868256
TI  - Probiotics--a helpful additional therapy for bacterial vaginosis.
AB  - BACKGROUND: Bacterial vaginosis is a condition of unknown etiology, associated
      with an imbalance of the normal vaginal microbiota, characterized by a high
      recurrence rate despite of classical therapy solutions. Probiotics are
      microorganisms, which taken in adequate amounts, are proven to bring health
      benefits in human and animal bodies, by re-establishing the normal flora at
      different levels. OBJECTIVE: The present article studies the possibility of using
      probiotic treatment as an adjuvant therapy for nonspecific vaginosis and reducing
      its recurrence rate. METHODS: We have evaluated the evolution of patients with
      bacterial vaginosis who received the classical antibiotic therapy and a probiotic
      product. The study group consisted of 173 non-pregnant, sexually active patients,
      20-45 years old, with no additional health problems and no contraceptive
      undergoing treatment, which have been admitted to the department of Obstetrics
      and Gynecology of the Bucharest Emergency University Hospital between 1.01.2012
      31.12.2012.The bacteriological evaluation was made on cervical and vaginal
      cultures. RESULTS: From a total of 173 patients, those who used probiotics oral
      capsules while taking an antibiotic had lower recurrence rates. More than a half
      of women who did not use any probiotic product had 3 or more relapse episodes per
      year. Vaginal capsules with probiotics have also proven to be useful in lowering
      the recurrence rate, but research is still needed. CONCLUSION: Probiotic products
      are proven to be a helpful adjuvant therapy for bacterial vaginosis, with no
      adverse outcomes.

PMID- 24868257
TI  - Cerebral microbleeds (CMBs) - relevance for mechanisms of cerebral hemorrhage-
      analysis of 24 MRI evaluated patients.
AB  - INTRODUCTION: The new MRI techniques introduced in the last decade allowed the
      detection of cerebral microbleeds (CMBs) in different groups of diseases: stroke,
      Alzheimer disease, vascular dementia or healthy people of advanced age. CMBs are
      radiologically defined as small, rounded, homogeneous, hypointense lesions on T2*
      weighed gradient-recalled echo (T2*-GRE) sequences. OBJECTIVE AND METHOD: We
      evaluated the prevalence, number and location of CBMs in a cohort of 26
      consecutive cerebral hemorrhage patients admitted in the National Institute of
      Neurology and Neurovascular Diseases. We also assessed the association between
      CMB, classical vascular risk factors and small vessel disease. RESULTS AND
      CONCLUSIONS: From the 26 patients, 2 patients had secondary intracerebral
      hemorrhage (ICH) (hemorrhage in metastasis, respectively a cavernoma). From the
      24 ICH patients 12 have had at least 1 CMB lesion. The average volume of the
      cerebral hemorrhage was larger in patients with CMBs, with a relative increase of
      42%. Small vessel disease was associated with a significant increase in the
      presence of CMBs (relative increase of 86%). In both cases, however, since the
      number of patients enrolled was small, the correlations did not reach statistical
      significance.

PMID- 24868258
TI  - Clinical, biological, echocardiographic and therapeutic determinants of the
      length of hospital stay of patients with acute heart failure.
AB  - HYPOTHESIS: The length of hospital stay (LOS) is a unanimously accepted measure
      of risk and treatment efficacy for in-patients. PURPOSE: Our aim was to identify
      the parameters with predictive value for the LOS of patients with acute heart
      failure (AHF). METHODS: We analyzed 125 patients consecutively admitted to our
      clinic with a slight male predominance (54.4%) and a mean age of 71.54 years.
      Patients were divided into groups according to the clinical form at presentation
      and left ventricular function. Mean LOS was of 8.74 days. RESULTS: Patients with
      LVEF<30% had a significantly higher LOS compared to those with LVEF>30%
      (F(2)=6.54, p<0.05). The same difference was discovered for those who received
      inotropic support (p<0.001), i.v. loop diuretic>140mg (p<0.001) as well as for
      those with QRS>160ms (p<0.05) or LBBB. The linear regression equation exposed a
      single significant statistical model indicating that the need for vasopressor
      amines, mean diuretic dose and PAAT<90msec explain 56% of the variance of LOS
      F(3.46)=20.55, p<0.001. The highest contribution to the model was achieved by the
      need for vasopressor amines (beta=0.66), with a unique contribution of 42% to the
      variance of the number of days of stay. The mean dose of diuretic had beta=0.27
      and a unique contribution to the model of 7.2%, followed by PAAT<90 msec with
      beta=0.26 and a unique contribution to the model of 7%. CONCLUSIONS: LOS is
      influenced by numerous parameters, some specific to certain clinical forms of AHF
      while others are independent, which is why evaluations on larger groups of
      patients are further needed.

PMID- 24868260
TI  - Schmidt's syndrome presenting as a generalised anxiety disorder: a case report.
AB  - Schmidt's syndrome or autoimmune polyglandurar syndrome type 2 represents an
      uncommon endocrine disorder composed by Addison's disease with autoimmune thyroid
      disease and/or type 1 diabetes mellitus. The syndrome usually affects women in
      the fourth decade of their lives. Prompt diagnosis and treatment can prevent
      serious complications. We present the case of a 64-year-old woman with
      generalised anxiety, facing socio-economic problems. Her symptoms attributed to
      stress led to a late diagnosis. Physicians involved have to be aware about
      endocrine disorders of which first manifestations may have atypical components
      mimicking mental health problems. 

PMID- 24868259
TI  - An Utstein style based on a reporting system of the emergency department's
      cardiopulmonary resuscitation in an emergency hospital in Romania.
AB  - RATIONALE: Different Utstein based reporting systems are used for research
      purpose in resuscitative medicine worldwide and resuscitation attempts data are
      available from different countries. In Romania, the only data available has been
      from the previous work in the Emergency Department of "Sf. Pantelimon" Emergency
      Hospital, since 2006. OBJECTIVE: This study was conducted to describe the
      characteristics of the cardiac arrest event in our Emergency Department (ED) and
      to identify factors associated with the outcome and the event itself. METHODS AND
      RESULTS: This descriptive study refers to the resuscitation attempts performed in
      the ED of our hospital between January 1st 2011 and December 31st 2011, following
      the Guidelines of the European Resuscitation Council 2010. The data used were
      gathered from the observational sheets. The reporting form used is Utstein-based,
      referring to the patient characteristics, event and outcome. A number of 81 cases
      have been analyzed; in 33 cases (40.74%), the cardiac arrest occurred out of the
      hospital. The return of the spontaneous circulation (ROSC) occurred in 25
      patients (30.86%), with 12% discharged alive. The most common cause of arrest was
      the myocardial infarction. The first rhythm monitored was non-shockable in 92.59%
      of the cases. However, 24 patients developed a shockable rhythm at some point
      during the resuscitation and 37.5% of these experienced ROSC. DISCUSSION: The
      Utstein- based reporting system used provides a standardized, comprehensive
      method for data collection. Further research is needed in order to obtain
      valuable data with statistic relevance. Conclusions related to the aspects of the
      population in the area the hospital serves can be drawn.

PMID- 24868261
TI  - Clinical, evolution and therapeutical considerations upon a case of
      fibrodysplasia ossificans progressiva (FOP).
AB  - Fibrodysplasia ossificans progressiva (FOP) is an autosomal dominant genetic
      transmitted disease, with a rare incidence (1-2 cases/million persons) and it
      usually affects female patients. Its manifestations include acute pain episodes
      that tend to repeat, involving the soft tissue and the axial muscles with later
      appearance of ectopic bone tissue in ligaments, joints and tendons. In the great
      majority of times, the skeletal modifications are observed at birth but the first
      clinical symptoms occur at 2-4 years old. The clinical symptoms include pain and
      inflammation of the soft tissue, sometimes associated with fever and cutaneous
      erythema, joint symptoms--pain, stiffness most frequently concerning the scapular
      and pelvic girdle, bone malformations--short hallux, microdactilia,
      kyphoscoliosis, thorax malformations. The diagnosis is established based on the
      clinical symptoms and the imagistic investigations: CT, MRI - which indicate the
      joint modification and the ectopic bone tissue. Muscular biopsy is not indicated
      as it leads to new lesions in the already traumatized areas.

PMID- 24868262
TI  - Is antibiotic prophylaxis mandatory after the insertion of levonorgestrel
      releasing intrauterine systemin order to decrease the risk of pelvic inflammatory
      disease?
AB  - OBJECTIVE: This study was undertaken in order to determine if antibiotic
      prophylaxis is mandatory, after the insertion of levonorgestrel-releasing
      intrauterine system in order to decrease the risk of pelvic inflammatory disease.
      MATERIALS AND METHODS: We prospectively evaluated 44 patients, admitted in the
      Bucharest Emergency Hospital between the 1i of February 2012 and the 1i of
      October 2012, in whom the levonorgestrel-releasing intrauterine system was
      inserted. The patients enrolled were divided into two groups. In group A, a
      number of 22 patients, received, after the insertion of levonorgestrel-releasing
      intrauterine system, 875mg Amoxicillin Trihydrate + 125 mg Potassium Clavulanate,
      a dose every 12 hours for 5 days. Group B was represented by the other 22
      patients who did not receive antibiotic prophylaxis. All patients were
      reevaluated at 4 and 12 weeks after the insertion of levonorgestrel-releasing
      intrauterine system. RESULTS: During the first 4 weeks after the insertion of
      levonorgestrel-releasing intrauterine system only two patients, one from group A
      and one from group B were diagnosed with pelvic inflammatory disease. At a second
      follow up visit - 12 weeks after the insertion of levonorgestrel-releasing
      intrauterine system, no other patient was diagnosed with pelvic inflammatory
      disease. CONCLUSION: Antibiotic prophylaxis is not mandatory, after the insertion
      of levonorgestrel-releasing intrauterine system in order to decrease the risk of
      pelvic inflammatory disease.

PMID- 24868263
TI  - Prediction factors for breast reconstruction postoperative complications.
AB  - Breast cancer is a major health problem that requires multiple forms of
      treatment, including surgery, adjuvant chemotherapy and radiotherapy and more
      recently, reconstructive surgery. The aim of this study is to determine the
      factors that can predict the chances of a patient having postoperative
      complications after breast reconstruction. 

PMID- 24868264
TI  - Correlations of hematological parameters with bone marrow findings in chronic
      lymphoproliferative disorders associated with hepatitis viruses.
AB  - BACKGROUND: Hepatitis B and C viruses' infections are often associated with
      hematological disorders in evolution, suggesting that these viruses have a
      tropism for peripheral blood and/or bone marrow cells. AIM: To analyze the
      hematological parameters and bone marrow findings in a group of patients
      diagnosed with chronic lymphoproliferative disorders (CLD) and hepatitis viruses
      B, C, D infections, which were included in the research grant (acronym LIMFO-VIR)
      between December 2007 and May 2010 in the Hematology Department of the Emergency
      University Hospital of Bucharest. METHODS AND RESULTS: Patients were diagnosed by
      using immunopathology according to the WHO criteria. The analyzed group included
      42 patients (both sexes), with the mean age of 60,35 years. The most frequent
      hematologic disease was non-Hodgkin's lymphoma 30/42 (71,42%), followed by
      chronic lymphocytic leukemia (16,66%) and Hodgkin's lymphoma (7,14%). Hepatitis
      viruses were distributed: 17/42 (40,47%) patients with HBV, 22/42 (52,38%) with
      HCV and 3/42 (7,14%) had a double/triple association of viruses. Most of the
      patients had an indolent type of disease - 27/42 (64,28%), whereas 15/42 (35,71%)
      had an aggressive one, pattern found both in the HBV and HCV infected groups. An
      abnormal bone marrow result was revealed in 32/42 (76,19%) patients, 19 (59,37%)
      of them being HCV infected. Myelodysplasia was found in 6/42(14,28%) patients,
      the majority being HCV infected, all having an indolent form of CLD. The
      antiviral therapy did not influence the hematological parameters (no significant
      differences were found between the groups with/without an antiviral therapy).
      DISCUSSIONS: Patients with hepatitis virus infections may associate neutropenia
      and thrombocytopenia; the mechanisms are thought to involve hypersplenism,
      autoimmune processes and antiviral therapy. We excluded the influence of
      chemotherapy, as the study was performed before the treatment. In our group,
      patients whether HBV or HCV infected, presented an isolated cytopenia. The
      abnormal bone marrow cellularity (increased or decreased) and dysplasia were
      found especially in the HCV group. There are studies showing no association
      between myelodysplasia and hepatitis viruses; others found a strong relation of
      these. One of the mechanisms of myelodysplasia could be a dysregulation of the
      immune system. Conclusions. Bone marrow/peripheral blood features correlate with
      the type of viral infection and HCV is more prone to develop additional
      hematological changes than HBV. The degree of bone marrow involvement by CLDs
      influences these features. We considered mandatory to perform a bone marrow
      analysis at the diagnosis of CLDs to stage and to establish if other bone marrow
      changes were present, a crucial aspect for therapy and outcome of the disease.
      The association between the hepatitis viruses - myelodysplasia- autoimmunity
      seems to have a role in the lymphoproliferative disorders etiology.
      ABBREVIATIONS: CLD - chronic lymphoproliferative disorders; NHL- non-Hodgkin's
      lymphoma, CLL- chronic lymphocytic leukemia, HL- Hodgkin's lymphoma, MDS -
      myelodysplastic syndrome, AML - acute myeloid leukemia.

PMID- 24868266
TI  - Increased prevalence of malignancy in adult mitochondrial disorders.
AB  - OBJECTIVES: there are indications that patients with a mitochondrial disorder
      (MID) develop malignomas or benign tumors more frequently than the general
      population. The aims of the study were to find out if the prevalence of tumors is
      actually increased in MID-patients and which of the malignomas or benign tumors
      are the most frequent. METHODS: The charts of MID-patients were retrospectively
      evaluated for the presence of malign or benign tumors. MID was diagnosed
      according to the modified Walker-criteria. RESULTS: Among the 475 MID-patients
      screened for tumors, at least a single malignoma was found in 65 patients
      (13.7%), and at least a single benign tumor in 35 patients (7.4%). Among those
      with malignancy, 22 were men and 43 women. Among those with a malignancy, 1 had
      definite MID, 9 probable MID, and 55 possible MID. The most common of the
      malignancies was breast cancer, followed by dermatological, gynecological, and
      gastrointestinal malignancies. The most frequent of the benign tumors was lipoma,
      followed by pituitary adenoma, meningeomas, carcinoids, and suprarenal adenomas.
      Compared to the general population, the prevalence of malignancies and of benign
      tumors was markedly increased. The female preponderance was explained by the
      frequent maternal inheritance of MIDs. CONCLUSIONS: Adult patients with a MID,
      particularly females, carry an increased risk to develop a malignancy or a benign
      tumor. Since malignancy is an important determinant for their outcome, these
      patients should be more accurately screened for neoplasms, not to overlook the
      point, at which an effective treatment can no longer be provided.

PMID- 24868267
TI  - The impact of modern endourological techniques in the treatment of a century old
      disease--medullary sponge kidney with associated nephrolithiasis.
AB  - The remarkable progresses of imagistic and interventional techniques that have
      been implemented during the last decades facilitated the diagnostic and allowed
      the treatment indication changes for numerous renal disorders. The purpose of the
      present lecture was to outline a data review concerning a renal anomaly first
      described one century ago as well as to evaluate the impact of endourologic
      technical progresses over the therapeutic management of the respective disease.
      The medullary sponge kidney (MSK) or Cacchi-Ricci disorder represents a
      disturbance in the renal development characterized by the cystic type dilation
      and diffuse precalyceal ducts ectasias. The disease is also known as precalyceal
      tubular ectasia, pyramidal sponge kidney or cystic dilation of the renal
      collecting ducts MSK patients are most often asymptomatic, the diagnosis being
      emphasized in light of the investigations imposed by related complications such
      as renal stones, urinary tract infections (pyelonephritis), renal tubes acidosis
      or urine concentration defects. 

PMID- 24868265
TI  - Predictive value of POSSUM score in surgery of acute abdomen in cirrhotic
      patients.
AB  - INTRODUCTION: As liver cirrhosis has an increasing incidence in the general
      population and the life expectancy for these patients has increased, surgery
      procedures practiced for acute abdomen in such category of patients are more
      frequent. AIM: To evaluate the predictive value of POSSUM score in cirrhotic
      patients undergoing abdominal surgery in emergency cases. MATERIAL AND METHOD: A
      prospective study based on 115 consecutive patients with liver cirrhosis
      hospitalized and operated in the first 24 hours from admission for acute abdomen.
      The patients' stratification was done by using Child Pugh score for liver
      cirrhosis. POSSUM score was calculated for each patient and postoperative
      outcomes were compared with prediction based on this score. Statistical data
      analysis was made by using the chi-square test and a p value of less than 0,05
      was considered to be statistically significant. RESULTS: There were 33 patients
      in stage Child A of cirrhosis, 54 in stage Child B and 28 in stage Child C. For
      Child A group, the POSSUM score had a satisfactory prediction in terms of
      morbidity and mortality. In advanced stages of liver cirrhosis, Child B and C,
      mortality had high rate and the observed outcomes were outside the area of POSSUM
      score prediction. CONCLUSIONS: POSSUM score offers a satisfactory prediction for
      morbidity and mortality in emergency abdominal surgery for patients in
      compensated stages of liver cirrhosis. In advanced stages of cirrhosis high
      levels of mortality cannot be predicted by using POSSUM score.

PMID- 24868268
TI  - Treatment in severe acute pancreatitis--still a reason of debate.
AB  - Surgical therapy in severe acute pancreatitis significantly evolved in the last
      10 to 20 years. The aim was to present the experience of the First Surgery Clinic
      within the University Emergency Hospital Bucharest, in the management of severe
      acute pancreatitis, following major etiopathogenic, diagnostic and treatment
      aspects. Our study was retrospective, longitudinal and descriptive, including a
      seven years period, between 2004 and 2010. 42 patients diagnosed with severe
      acute pancreatitis have been admitted and operated. 25 were male, representing
      59,52% and 17 female, respectively 40,47%. 55% of the patients were operated more
      than 11 days after the hospitalization, 25% were operated in the 4 to 10 days
      interval and 20% were operated in emergency conditions: immediate emergency
      (first 24 hours) or delayed emergency (24-72 hours). Mortality reported to the
      moment of surgery was 60% for the patients operated in the first 24 hours, 66,67%
      for the 24-72 hours operation interval, 30% for the patients operated between 4
      10 days from the admission and 18,18% for operations performed after more than 11
      days . CONCLUSION: mortality significantly decreased when the surgical moment was
      postponed by using intensive therapy, over 11 days from admission. We reconfirm
      the optimal temporization attitude of surgery, until the infection of necrosis or
      appearance of pancreatic abscess.

PMID- 24868270
TI  - Zenker's diverticulum: aetiopathogenesis, symptoms and diagnosis. Comparison of
      operative methods.
AB  - Zenker's diverticulum is an alimentary tract pouch localized in the area of the
      upper esophageal sphincter. Treatment procedure complications and coexisting
      diseases constitute a serious diagnostic and therapeutic problem. Characteristic
      symptoms and signs facilitate differential diagnosis, simultaneously being real
      patient maladies. There are many treatment procedures leading to pouch septum
      reduction and decrease of upper esophageal sphincter pressure. After years of
      experience in operating and endoscopic treatments we found it necessary to
      compare these different methods. 

PMID- 24868269
TI  - Biomarkers in management of inflammatory bowel disease.
AB  - In recent years the use of faecal and serologic biomarkers has been evaluated in
      the diagnosis and management of inflammatory bowel disease (IBD). Faecal
      calprotectin (FC) has been proposed as a surrogate marker for intestinal
      inflammation; elevated concentrations in IBD patients have been confirmed in
      numerous studies. Already available rapid calprotectin tests help to
      differentiate between IBD and irritable bowel syndrome. Faecal calprotectin
      greatly correlates with endoscopic activity scales and reflects the mucosal
      healing; thus in patients in clinical remission high levels of it correlate with
      increased risk of disease relapse in the following 12 months. Adapting the
      calprotectin assay as a screening test before colonoscopy enables a significant
      reduction in endoscopic procedures. ANCA/ASCA antibodies have been used in IBD
      diagnosis and to distinguish CD from ulcerative colitis (UC). Lactoferrin and
      S100A12 protein were also used to assess the disease activity. This review aims
      to present the actual potential of biomarker assays for faster diagnosis of IBD
      and their ability to monitor the disease course, predict exacerbations and
      improve the way IBD is managed. 

PMID- 24868271
TI  - Aetiopathogenesis of liver changes in the course of cystic fibrosis, considering
      disturbances of the bile acid profile as well as genetic and immunological
      factors.
AB  - Liver changes observed in the course of cystic fibrosis comprise a group of
      complex processes of fibrosis, inflammation, remodelling, apoptosis and
      cholestasis as a result of abnormal functioning of the cystic fibrosis
      transmembrane conductance regulator (CFTR) protein, immunological reactions and
      response to oxidation stress. Liver lesions are only observed in 5-20% of
      patients with diagnosed cystic fibrosis; however, they increase mortality, reduce
      the lifespan and deteriorate the quality of life. Liver diseases are the most
      common extrapulmonary causes of death in patients with cystic fibrosis. The aim
      of the study was to analyse the hitherto performed studies on the
      aetiopathogenesis of liver changes in the course of cystic fibrosis considering
      disturbances of the bile acid profile as well as genetic and immunological
      factors. 

PMID- 24868272
TI  - Butyric acid in functional constipation.
AB  - Butyric acid, a short-chain fatty acid, is a major energy source for colonocytes.
      It occurs in small quantities in some foods, and in the human body, it is
      produced in the large intestine by intestinalkacteria. This production can be
      reduced in some cases, for which butyric acid supplementation may be useful. So
      far, the use of butyric acid in the treatment of gastrointestinal disorders has
      been limited because of its specific characteristics such as its rancid smell and
      rapid absorption in the upper gastrointestinal tract. In the Polish market,
      sodium butyrate has been recently made available, produced by the modern
      technology of microencapsulation, which allows the active substance to reach the
      small and large intestines, where butyrate easily dissociates into butyric acid.
      This article presents the potential beneficial mechanisms of action of butyric
      acid in defecation disorders, which are primarily associated with reductions in
      pain during defecation and inflammation in the gut, among others. 

PMID- 24868273
TI  - Treatment results of gastrointestinal perforation after endoscopic retrograde
      cholangiopancreatography.
AB  - INTRODUCTION: Duodenal perforation, damage to common bile duct or ampulla of
      Vater complicates from 0.7% to 10% of endoscopic retrograde
      cholangiopancreatography (ERCP) procedures. This complication is associated with
      high risk of contracting fatal diseases and death. As the endoscopic and
      minimally invasive treatment methods develop and gain popularity, it becomes
      increasingly important to determine the correct procedure in the event of
      gastrointestinal perforation after ERCP. AIM: To present the results of treatment
      of gastrointestinal perforation after ERCP and indicate the correct procedure for
      such cases. MATERIAL AND METHODS: The material includes 19 patients who underwent
      ERCP in the years 2008-2011 and were subsequently diagnosed with duodenal
      perforation (except for duodenal bulb) and common bile duct (CBD). Women
      accounted for 68% of patients (13/19), while men constituted 32% (6/19). The mean
      age of patients was 66.6 years old. Indications for ERCP included cholelithiasis
      in 95% of cases and bile duct strictures in the remaining 5%. Treatment was
      conditional on the result of X-ray examination of the abdominal cavity, followed
      by computed tomography with aqueous contrast medium administered orally. RESULTS:
      Four patients were diagnosed with intraperitoneal perforation and 15 patients
      with retroperitoneal perforation. In the patient group with retroperitoneal
      perforation the contrast media leakage (10 patients) required surgical
      intervention - the perforation site was located in 5 cases; in the other 5 the
      site could not be found. With the absence of active contrast media leakage in
      computed tomography (CT) (5 patients) conservative treatment was applied. Four
      patients with intraperitoneal perforation were referred for operative treatment.
      In patients under conservative treatment no complications were observed and the
      average hospitalization time was 9 days. Among patients with retroperitoneal
      perforation, who had undergone surgical treatment, complications occurred in 3
      cases. The average hospitalization time in the group in which the perforation
      site was located was 16 days, while in the group with an unidentified perforation
      site it was 17 days. Patients with intraperitoneal perforation were given
      operative treatment, with the average hospitalization time of 12 days.
      CONCLUSIONS: Each patient with suspected post-ERCP perforation should undergo CT
      of the abdominal cavity with aqueous contrast medium administered orally. In the
      event of no contrast leak in patients with retroperitoneal duodenal perforation,
      conservative treatment should be applied. In the case of retroperitoneal
      perforation with active contrast media leakage outside the gastrointestinal
      tract, and in the case of intraperitoneal perforation, an immediate surgical
      intervention is recommended.

PMID- 24868274
TI  - Bowel preparation for colorectal surgery: with and without mannitol.
AB  - INTRODUCTION: In our country due to some limitations, mannitol is widely used for
      bowel preparation. Bowel preparation with mannitol has several side effects. AIM:
      To compare complication of mechanical bowel preparation with and without
      mannitol. MATERIAL AND METHODS: This case control study was carried out in Imam
      Khomeini and Abuzar children's hospitals. Sixty cases of patients who underwent
      colorectal surgery were included in this study. Pull-through, colostomy closure,
      and anorectoplasty were the surgical procedures. Subjects were randomly placed in
      the case or control group. Infection, electrolyte disturbances, fever, and
      leukocytosis were recorded. Multivariate analysis was done using PRISM. Odds
      ratio was calculate with CI = 95%. RESULTS: Fourteen boys and 16 girls were
      included in group I. Ten boys and 20 girls were included in group II. Twenty
      colostomies, 6 pull-throughs, and 4 anorectoplasties were performed in group I.
      Twenty-one colostomies, 5 pull-throughs, and 4 anorectoplasties were done in
      group II. Mean age of the patients was 2.63 +/-1.9 and 2.66 +/-1.68 for group I
      and group II respectively (p = 0.262). Following bowel preparation with mannitol,
      14 patients had mild fever with mean body temperature of 38.1 degrees C. Three
      subjects had postsurgical fever within 48 h of surgery. In group II,
      postoperative fever was found in 2 subjects. CONCLUSIONS: Hypernatremia,
      hypokalemia, and leukocytosis were more common in patients who underwent bowel
      preparation with mannitol.

PMID- 24868275
TI  - Insulin, insulin-like growth factor 1 and insulin-like growth factor binding
      protein 3 serum concentrations in patients with adenomatous colon polyps.
AB  - INTRODUCTION: Insulin stimulates colonic mucosal cells proliferation directly and
      by influencing the concentration of insulin-like growth factor 1 (IGF-1) and
      insulin-like growth factor binding protein 3 (IGFBP-3). AIM: To estimate serum
      concentrations of insulin, IGF-1, and IGFBP-3 and to determine the relationships
      between them and colorectal adenoma location, dysplasia grading, histological
      type, and size. MATERIAL AND METHODS: The study included 60 patients with
      colorectal adenomatous polyps found on colonoscopy and confirmed pathologically.
      The control group consisted of 30 individuals with no positive findings on
      colonoscopy. All patients had their blood drawn for assessment of insulin, IGF-1,
      and IGFBP-3 serum concentrations. RESULTS: One hundred and nine adenomas (6-40 mm
      in size) were found in 60 study patients. The average age of patients with
      multiple polyps was significantly higher than that of patients with single
      pathologies (61.1 vs. 56.7 years respectively (p < 0.05)). A higher adenoma
      incidence rate was observed in the distal portion of the colon than the proximal
      one (50 vs. 10 polyps respectively (p < 0.01)). Higher serum levels of IGF-1 and
      IGFBP-3 were found in patients with adenomatous polyps than in the control group.
      The average IGF-1 concentration in patients with adenomas located proximally was
      also significantly higher compared to those located distally (p < 0.05). The
      insulin concentration was similar in both groups and not related to clinical data
      of patients. CONCLUSIONS: The results indicate the role of IGF-1 and IGFBP-3 in
      early carcinogenesis of the large intestine, and IGF-1 particularly in malignant
      transformation in the proximal part of the organ.

PMID- 24868276
TI  - Laparoscopic versus open management of duodenal perforation: a comparative study
      at a District General Hospital.
AB  - INTRODUCTION: Duodenal perforation is one of the common pathologies in patients
      presenting in emergency with acute abdominal pain in an emergency ward and
      requires prompt surgery as life saving and curative intervention. The present
      study was conducted to determine whether the minimal access approach by
      laparoscopy was equally feasible as the open method. AIM: To compare laparoscopic
      vs. open management duodenal perforation in all aspects. MATERIAL AND METHODS: 
      INCLUSION CRITERIA: patients presenting to the emergency ward with acute pain in
      the abdomen with clinical signs of peritonitis and air under the diaphragm on X
      ray abdomen standing were selected. Exclusion criteria were: patient age < 15
      years and > 70 years, presentation > 2 days, shock with systolic blood pressure <
      90 mm Hg which did not improve after hydration with 2000 ml of Ringer lactate
      solution, respiratory distress, history of cardiac disorder or respiratory
      disorders such as ischemic heart disease, arrhythmias, chronic obstructive
      pulmonary disease or asthma, bleeding and clotting disorders, pregnancy in
      females, previous upper abdominal surgery, and intra-operatively patients having
      perforation other than duodenal perforation. After excluding patients fitting the
      above criteria, two groups - test and control - were formed. RESULTS: We found
      that complications both early and late were significantly fewer in patients
      treated by laparoscopy. Thus laparoscopy was both feasible and had comparable
      mortality and leakage rate. CONCLUSIONS: Laparoscopic management of perforated
      duodenal ulcer is feasible, effective and decreases morbidity and overall
      treatment time and cost if performed in properly selected patients.

PMID- 24868277
TI  - Retrospective analysis of clinical problems concerning acute pancreatitis in one
      treatment center.
AB  - INTRODUCTION: Severe acute pancreatitis is still a difficult clinical problem, it
      is a challenge for medical teams, which should include the strategy of
      personalized medicine. In clinical observations, among patients with the
      fulminating course of acute pancreatitis developed during the first hours leading
      to irreversible multiorgan failure and death. AIM: To evaluate the frequency of
      occurrence and analyze the progression and treatment of severe acute pancreatitis
      (AP) in patients hospitalized during the years 2004-2010 at the Clinical Surgery
      Ward. MATERIAL AND METHODS: One thousand and fifty patients treated for AP were
      included in the study; 97 patients with severe AP were subjected to a detailed
      clinical analysis. RESULTS: The average age of the patients was 52.8 years.
      Relapses occurred in 14.9% of patients. The severe form of acute pancreatitis was
      diagnosed in 97 patients, which accounts for 9.2% of all the illnesses, and
      occurred significantly more often in male patients (p < 0.01). The most frequent
      etiological factors were cholelithiasis (46.4%), and idiopathic pancreatitis
      (27.8%); alcohol consumption was responsible for 22.7% of the cases; the
      occurrence of both a bile-derivative and alcoholic factor was found in 3.1% of
      the cases. A worsening clinical state resulted in laparotomy in 26 patients
      (26.8%), and re-laparotomy in 5 patients. Necrosectomy was performed on 15
      patients, of whom 33.3% died due to complications. The total mortality in severe
      AP was 38.1%. The average age of the deceased was 66.5. Early deaths within 14
      days were noted in 78.4% of patients (n = 29) who died due to severe AP.
      CONCLUSIONS: Severe AP in spite of implementing modern diagnosis and treatment
      methods is still associated with a high risk of death. Constant clinical
      observation and use of available prognostic scales are essential in improving AP
      prognoses.

PMID- 24868278
TI  - Choledochal or hydatid cyst: a clinical pitfall.

PMID- 24868279
TI  - The giant in the stomach - trichobezoar.

PMID- 24868280
TI  - Etiology, diagnosis and treatment of infectious esophagitis.
AB  - Infectious esophagitis may be caused by fungal, viral, bacterial or even
      parasitic agents. Risk factors include antibiotics and steroids use, chemotherapy
      and/or radiation therapy, malignancies and immunodeficiency syndromes including
      acquired immunodeficiency syndrome. Acute onset of symptoms such as dysphagia and
      odynophagia is typical. It can coexist with heartburn, retrosternal discomfort,
      nausea and vomiting. Abdominal pain, anorexia, weight loss and even cough are
      present sometimes. Infectious esophagitis is predominantly caused by Candida
      species. Other important causes include cytomegalovirus and herpes simplex virus
      infection. 

PMID- 24868282
TI  - Achievements of Polish doctors in gastrodiaphanoscopy at the turn of the 19(th)
      and 20(th) centuries.
AB  - Diaphanoscopy/transillumination, the method of shining a bright light through
      tissues, was devised in the mid-19(th) century and developed after the invention
      of the light bulb by T.A. Edison. Benjamin Milliot was the first to examine the
      stomach by means of an incandescent platinum wire. The experiments conducted by
      Max Einhorn using a device consisting of a Nelaton catheter with an inserted
      light bulb, were valuable. In Poland the method of gastrodiaphanoscopy was
      popularized by Teodor Heryng, Mikolaj Rejchman and by Warsaw doctors. They used a
      diaphanoscope consisting of a gutta-percha probe distally equipped with a metal
      attachment with a light bulb hidden in it and with a so-called cooling device.
      The examination would usually be conducted in the standing position after the
      stomach had been filled with water. Light patches corresponding to the stomach's
      lower and side boundaries would be obtained. Rejchman's observation, that such a
      contractile and flexible organ as the stomach, changing its volume and position,
      is bound to change its light image, was correct. Heryng's and Rejchman's research
      inspired the foreign researchers Renvier, Leopold Kuttner and John Jacobson.
      Extensive research was subsequently conducted by C.A. Meltzing and Wilhelm
      Schwartz. Diaphanoscopy would also be performed by Walery Jaworski, the pioneer
      of gastrology. He was particularly interested in transillumination of the
      stomach, peritoneum and omentum tumours. Eugeniusz Kozierowski, a practicing
      physician from Gorlice, diagnosed neoplastic pylorostenosisusing this method.
      Gastrodiaphanoscopy is a historical method, now of no value against
      gastroendoscopy and the state-of-the-art methods of image diagnostics. 

PMID- 24868281
TI  - Pragmatically on the sense of taste - a short treatise based on culinary art.
AB  - The sense of taste is essential for proper functioning of the organism. The
      authors describe, in an accessible way, the complex mechanisms of taste
      perception. The structure of particular taste receptors, variants of their
      activation, as well as physical and chemical factors modifying the sensation of
      taste, are presented. Exquisite culinary examples are given in order to
      facilitate the reader with the understanding of why, at the level of the cerebral
      cortex, a virtually infinite number of combinations of taste sensations can be
      perceived. The discourse is spiced up by reflections of the eminent philosopher
      of taste, J.A. Brillat-Savarin, who convinces us that food intake should be not
      only a physiological act, but also a refined pleasure. 

PMID- 24868283
TI  - Butyric acid in irritable bowel syndrome.
AB  - Butyric acid (butanoic acid) belongs to a group of short-chain fatty acids and is
      thought to play several beneficial roles in the gastrointestinal tract. Butyric
      anion is easily absorbed by enteric cells and used as a main source of energy.
      Moreover, butyric acid is an important regulator of colonocyte proliferation and
      apoptosis, gastrointestinal tract motility and bacterial microflora composition
      in addition to its involvement in many other processes including immunoregulation
      and anti-inflammatory activity. The pathogenesis of irritable bowel syndrome
      (IBS), the most commonly diagnosed functional gastrointestinal condition, is
      complex, and its precise mechanisms are still unclear. This article describes the
      potential benefits of butyric acid in IBS. 

PMID- 24868284
TI  - Socio-demographic characteristics of patients with diagnosed functional
      dyspepsia.
AB  - INTRODUCTION: The term "dyspepsia" comes from the Greek words "dys' and 'peptin",
      which maen "ill digestion" or indigestion, although this set of symptoms in the
      adult clinic has little to do with the digestion or absorption process, and
      refers more to ailments related to the upper section of the gastrointestinal
      tract. AIM: Assessment of the frequency of functional dyspepsia diagnosis, the
      characteristics of the group and an attempt to identify the accompanying
      symptoms, assessment of histological lesions and an attempt to answer question
      about the efficiency of anti-secretory and eradication therapy. MATERIAL AND
      METHODS: The study involved patients reporting for gastrofiberscopic examination
      due to dyspeptic ailments. A total of 230 patients were examined, including 140
      women and 90 men, above 18 years of age. They underwent endoscopic examination,
      and a selected group with functional dyspepsia (FD), analysed using the 'Gast'
      questionnaire, underwent eradication therapy or proton pump inhibitors.
      Statistical analysis involved chi(2) and Fischer's test. RESULTS: The study
      involved 230 individuals with dyspeptic disorders. The largest age group was 46
      60 years. These patients reported due to their ailments mostly in autumn and
      winter. The differentiated group with FD included 53 patients (23% of the
      clinical population). 69.8% of the FD group was infected with Helicobacter pylori
      (with 81.2% of the whole population, respectively). Individuals with FD reported
      improvement more often after being administered drugs to decrease gastric
      secretion, more often declared post-elementary education and suffered from non
      gastric ailments yet still described their state of health as good. No positive
      therapeutic effect of eradication was noticed during the 6-month observation.
      CONCLUSIONS: Due to the very high ratio of subjects with functional dyspepsia,
      also observed in the study sample, and the influence of civilization progress, we
      should expect increasing frequency of occurrence of this problem.

PMID- 24868285
TI  - Do intestinal parasitic infestations in patients with clinically acute
      appendicitis increase the rate of negative laparotomy? Analysis of 3863 cases
      from Turkey.
AB  - INTRODUCTION: Acute appendicitis is the most frequently observed disease
      requiring emergency surgery. The role of parasites in its pathogenesis has long
      been discussed. The signs of the parasitic infestations can mimic the signs of
      acute appendicitis. Therefore, it can cause a negative laparotomy. AIM: To
      evaluate the parasitic infestations of the appendix vermiformis whether increas
      the rate of negative laparotomy. MATERIAL AND METHODS: The histopathology results
      of a total of 3863 patients who underwent appendectomy with clinically acute
      appendicitis were evaluated retrospectively. All appendectomy materials in which
      parasites were observed were evaluated with respect to the nature of the
      parasites and the findings of inflammation. Cases in which parasite tissue
      fragments and/or eggs as well as findings of inflammation were
      histopathologically observed in the appendix lumen were diagnosed with parasitic
      appendicitis. RESULTS: Evidence of parasites was observed in 19 (0.49%) of the
      evaluated appendectomy materials. In 9 (47.3%) of these specimens that had
      evidence for parasites, findings for acute appendicitis and localized peritonitis
      were identified. Findings of acute appendicitis had not been identified in the
      other ten (52.7%) of the specimens. Enterobius vermicularis was the most
      frequently identified parasite. CONCLUSIONS: In parasitic acute appendicitis,
      appendectomy in itself is not sufficient for treatment. Pharmacological treatment
      should also be administered after surgery. Patients should be evaluated prior to
      surgery for parasites, and diagnosis of acute appendicitis should be considered
      more cautiously in order to avoid negative laparotomies.

PMID- 24868286
TI  - Occurrence of autoantibodies for gastrointestinal autoimmune diseases in children
      with common variable immune deficiency and selected IgA deficiency.
AB  - INTRODUCTION: Selected IgA deficiency (IgAD) and common variable immune
      deficiency (CVID) are humoral immunity deficiencies frequent in children. In both
      these types of immunodeficiency, autoimmune diseases are present in 20-30% of
      patients, but the disease profiles are different between adults and children.
      Autoimmune diseases of the gastrointestinal tract (IBD) and celiac disease are
      typical for children with IgAD and CVID. Diagnosis is based on clinical symptoms,
      histology of jejunum and antibodies often preceding the onset of disease.
      However, the diagnosis of IBD and celiac disease is difficult in immune
      deficiency patients due to weaker or absent production of antibodies, and
      different jejunum histology, particular in CVID patients. AIM: Detection of
      antibodies for autoimmune diseases in children with diagnosis of CVID and IgAD.
      MATERIAL AND METHODS: The study included 43 children with CVID and 63 children
      with IgAD diagnosis. Antibodies typical for celiac disease (for endomysium,
      tissue transglutaminase and gliadin) were tested in IgA class (CVID patients),
      IgG class (IgAD, CVID patients) and found in 16 patients (3 - CVID, 13 - IgAD).
      RESULTS: Antibodies for IBD (for Saccharomyces cerevisiae antigen - ASCA, goblet
      cells - Gab, neutrophil's cytoplasm - ANCA, pancreatic cells - Pab) were noted in
      17 patients (7 - CVID, 10 - IgAD). Celiac disease was diagnosed in two children
      with mild and unspecific clinical symptoms followed by introduction of a gluten
      free diet. The remaining children with present antibodies but without clinical
      symptoms involving the gastrointestinal tract are under careful clinical
      observation with antibody assay every 6 months. CONCLUSIONS: The antibodies are
      produced despite impaired humoral immunity but the level might be low so the
      lower limit of positive results is postulated.

PMID- 24868287
TI  - An analysis of the correlation of clinical, endoscopic and histological
      classifications in Crohn's disease.
AB  - INTRODUCTION: The precise evaluation of Crohn's disease (CD) activity is
      difficult mainly due to the complex symptoms of the disease. Establishing
      correlations between the most widely used scales of CD clinical, endoscopic and
      histopathological activity might help to identify the most accurate scale in the
      assessment of the course of CD. AIM: Comparison of the results of clinical,
      endoscopic and histological scales of CD activity, i.e. (Crohn's Disease Activity
      Index (CDAI) score, Montreal Classification, Crohn's Disease Endoscopic Index of
      Severity (CDEIS) and D'Haens classification). MATERIAL AND METHODS: A group of 62
      patients with CD was examined. All individuals underwent medical interview and
      physical examination. All patients had colonoscopy, at which the extent of the
      disease was analysed according to Montreal Classification and intensity of
      mucosal lesion described by CDEIS scale. Biopsy samples were taken during
      colonoscopy. Crohn's disease activity was evaluated by clinical scales (Montreal
      Classification - A and B, CDAI), endoscopic scales (Montreal Classification - L,
      CDEIS) and histopathological classification by D'Haens. RESULTS: The results of
      histopathological activity scale of CD by D'Haens correlated only with the
      results of endoscopic classification CDEIS. The results of CDEIS correlated also
      with parameter B of Montreal Classification. The analysis of Montreal
      Classification parameters showed correlations between the age of disease onset
      (A) and localization of the disease (L). Additionally, correlation of parameter A
      (age of onset) and B (behaviour of the disease) of Montreal Classification was
      observed. The values of clinical CDAI scale correlated only with parameter B of
      Montreal Classification (behaviour of the disease). CONCLUSIONS: There was a
      significant correlation between the histological (D'Haens) classification and
      endoscopic scale (CDEIS), but their results did not correlate with clinical
      scales. There was no consistent correlation between the clinical scales
      themselves however the correlations concerned only some parameters assessed,
      which may be the result of subjective clinicians evaluation of CD activity.

PMID- 24868288
TI  - Fasting and postprandial levels of ghrelin, leptin and insulin in lean, obese and
      anorexic subjects.
AB  - INTRODUCTION: Ghrelin, leptin and insulin are involved in neurohormonal
      regulation of energetic homeostasis. AIM: We investigated the correlation between
      nutritional status and plasma levels of leptin, ghrelin and insulin in lean,
      obese and anorexic subjects. MATERIAL AND METHODS: Nineteen obese and 18 anorexic
      adults were enrolled in the study. Seventeen adults with normal body mass index
      (BMI) served as controls. Blood samples were taken twice: before breakfast and 2
      h after breakfast. Fasting and postprandial ghrelin, leptin and insulin were
      examined. The following correlations were estimated: between BMI and basal level
      of tested hormones, between insulin and ghrelin, and between insulin and leptin.
      The threshold level of significance was p <= 0.05 for all calculations. RESULTS:
      Basal insulin level was lowest in anorexic patients and greatest in obese
      subjects. Fasting plasma ghrelin was lower in obesity and higher in anorexia as
      compared with the controls. Comparing with controls, fasting leptin levels were
      higher in obese and lower in anorexic subjects. There was positive correlation
      between BMI and basal leptin level in obesity. A significant postprandial
      increase was noted for insulin in all studied groups. Increased leptin and
      decreased ghrelin levels were detected 2 h after a meal in the control group. In
      obese patients, postprandial leptin was lower than before food intake, and
      fasting leptin showed positive correlation with basal insulin level. CONCLUSIONS:
      Basal plasma ghrelin, leptin and insulin levels differ according to nutritional
      status. Impaired ghrelin and leptin secretion and insulin sensitivity may be
      involved in the pathogenesis of eating disorders.

PMID- 24868289
TI  - Family recognition of celiac disease.
AB  - Celiac disease is a permanent intolerance to gluten that leads to small-bowel
      mucosal villous atrophy during autoimmune processes in genetically predisposed
      individuals. At present the diagnosis of celiac disease is based on
      characteristic clinical symptoms, the results of serological investigations
      (tissue transglutaminase ten times the upper limit of normal, presence of
      antiendomysial antibodies - EMA) and positive results of genetic examinations.
      The aim of this study is to present a medical history of a family in which the
      mother and younger son were diagnosed with celiac disease (confirmed by genotype
      examination). Before the genetic examination, the father and the elder son were
      also suspected of suffering from this disease (they were on gluten-free diets).
      The authors emphasize the usefulness of HLA-DQ2/DQ8 determination in first-degree
      relatives of celiac patients. 

PMID- 24868290
TI  - Exercise-induced vomiting.

PMID- 24868291
TI  - Biosimilar medicines - their use in the treatment of inflammatory bowel diseases.
      Position statement of the Working Group of the Polish National Consultant in
      Gastroenterology.
AB  - Biological medical products are drugs whose active components are produced only
      by living, genetically modified organisms or live cell cultures. Patents and
      exclusivity for most biopharmaceuticals has either expired or will expire soon,
      which enables biotechnological companies to introduce similar biological
      products. The problem of replacing a biological medicine with a biosimilar in the
      course of therapy remains open. In this statement, the Working Group of the
      Polish National Consultant in Gastroenterology, in the absence of data regarding
      bioequivalence in patients with inflammatory bowel disease, does not recommend
      switching from original biological medicine to its biosimilar analogue in the
      course of treatment in inflammatory disease patients; however, this may change
      after receiving the results of controlled studies regarding bioequivalence in
      this group. 

PMID- 24868292
TI  - The influence of natural feeding on human health: short- and long-term
      perspectives.
AB  - Breastfeeding is the most appropriate way to nourish infants. It promotes proper
      physical and intellectual development of the child. Human milk is unique and
      impossible to replicate with any other kind of food. However, using maternal milk
      not only has beneficial effects on the infant's health but it can also help to
      prevent illnesses in adulthood. Breastfeeding improves immunity and consequently
      decreases the occurrence of infections, especially those of the gastrointestinal
      tract and respiratory tract. Moreover, it helps to reduce the risk of some
      disorders such as allergies, diabetes mellitus type 1, obesity and arterial
      hypertension. 

PMID- 24868294
TI  - Dietary recommendations for patients with nonalcoholic fatty liver disease.
AB  - Changes to patients' lifestyle, especially a modified dietary approach, play a
      key role in the treatment of nonalcoholic fatty liver disease (NAFLD). A
      balanced, limiting and individually tailored nutritional scheme enables weight
      loss and an improvement in the clinical picture of NAFLD. According to
      nutritional recommendations for patients with NAFLD, carbohydrates should
      comprise 40-50% of total dietary energy. It is advisable to increase the amount
      of complex carbohydrates rich in dietary fibre. A major role in the aetiology of
      NAFLD is played by excessive intake of fructose, which is related to the rise in
      consumption of nonalcoholic beverages among subjects in developed countries. Fat
      intake should comprise < 30% of daily calories. It is essential to increase
      consumption of food products rich in mono- and polyunsaturated fatty acids.
      Ingestion of protein should constitute 15-20% of total energy. 

PMID- 24868295
TI  - Oral health and liver function in children and adolescents with cirrhosis of the
      liver.
AB  - INTRODUCTION: People with cirrhosis of the liver are predisposed to developing
      oral lesions. The occurrence and type of lesion depend on the degree of liver
      function impairment and its type, and on the severity and duration of systemic
      diseases. In children, the age at which the early symptoms of liver disease are
      experienced is also of great importance. AIM: To assess the prevalence of oral
      pathological lesions in children and adolescents with cirrhosis of the liver, and
      their correlation with the degree of liver function impairment. MATERIAL AND
      METHODS: Clinical and laboratory results of liver function tests (Model of End
      Stage Liver Disease/Score of Paediatric End-Stage Liver Disease, Child-Pugh
      score) were assessed in 35 patients with cirrhosis of the liver. The average age
      of the patients was 10.7 +/-4.74 years. All patients also had their oral cavities
      examined (mucosa, gingiva - GI, hygiene - PLI, teeth - dmft/dmfs and DMFt/DMFs,
      DDE Index and Candida spp. presence) and this was then correlated to the degree
      of liver function impairment. RESULTS: According to the Child-Pugh scale, 16
      patients were class A and 19 were class B/C. Jaundice during the first 3 years of
      life occurred in 9 patients. Mucosal lesions were found in 26 out of 35 patients
      (74%), including 10 out of 16 (63%) in Child-Pugh group A, and 16 out of 19 (84%)
      in group B/C (NS - non significant). Oral candidiasis occurred more often in
      class B/C than in class A (47.4% vs. 12.5%; p < 0.05). The GI index (Gingival
      Index) and PLI index (Dental Plaque Index) did not differ between the groups (A
      vs. B/C) but correlated in the whole group (R = 0.58) as well as in subgroups A
      (R = 0.65) and B/C (R = 0.59). Dmft/dmfs and DMFt/DMFs indexes did not differ
      between groups A and B/C, and neither did the DMFt/DMFs in patients with/without
      enamel defects. CONCLUSIONS: Oral mucosal lesions are commonly found in children
      with cirrhosis of the liver. Advanced liver disease promotes oral candidiasis.
      Severity of gingivitis correlates with the presence of dental plaque.

PMID- 24868293
TI  - Coexistence of coeliac disease and type 1 diabetes.
AB  - There is a selective review of the literature concerning the coexistence of
      coeliac disease and type 1 diabetes mellitus. This review focuses on the
      principles of serological tests towards coeliac disease in patients with type 1
      diabetes mellitus and metabolic control measures as a result of a gluten-free
      diet. 

PMID- 24868296
TI  - Evaluation of HLA-DQ2/DQ8 genotype in patients with celiac disease hospitalised
      in 2012 at the Department of Paediatrics.
AB  - INTRODUCTION: Celiac disease (CD) is a permanent intolerance to gluten that
      occurs in genetically predisposed individuals and leads to small intestinal
      mucosa damage. According to ESPGHAN guidelines from 2012, CD can be diagnosed in
      a patient with characteristic clinical symptoms, in whom, anti-tissue
      transglutaminase antibodies (> 10 times the upper limit) are found, endomysial
      antibodies (EMA) is confirmed and a positive genetic test is obtained. In these
      conditions no small-bowel biopsies are required. AIM: Evaluation of the presence
      of HLA-DQ2 and HLA-DQ8 haplotypes in children with previously diagnosed CD,
      hospitalised in 2012 at the Department of Paediatrics and Immunology and/or the
      Gastroenterological Outpatient Clinic, and their relatives. MATERIAL AND METHODS:
      Blood samples of 22 subjects, including 9 children with CD diagnosed on the basis
      of clinical symptoms, serological investigations and small-intestine biopsy, 7
      diagnosed on the basis of clinical symptoms and serological investigations, 2
      with the suspicion of CD on the basis of clinical symptoms and 4 relatives of a
      child with CD. METHODS: HLA-DQ2/DQ8 test, automatic evaluation by EUROArrayScan.
      RESULTS: The presence of HLA-DQ2 and/or HLA-DQ8 genotype was confirmed in 16
      children with CD diagnosed on the basis of clinical symptoms and serological
      tests with/without intestinal biopsy, in 2 with the suspicion of CD and in 1
      relative of a celiac child. CONCLUSIONS: The evaluation of HLA-DQ2/DQ8 haplotype
      confirms the genetic predisposition to CD in subjects with the disease diagnosed
      previously on the basis of clinical symptoms, serological tests or intestinal
      biopsy. Genetic testing is particularly indicated for the diagnosis of CD in
      infants consuming gluten for a short time and in small amounts.

PMID- 24868297
TI  - Distribution of haematological indices among subjects with Blastocystis hominis
      infection compared to controls.
AB  - INTRODUCTION: Some studies suggest Blastocystis hominis is a potentially
      pathogenic protozoa. Blastocystis hominis contributed to anaemia in children aged
      8-10 years old in one study. AIM: To compare haematological indices in cases with
      blastocystis hominis infection with healthy controls. MATERIAL AND METHODS: From
      2001 to 2012, 97600 stool examinations were done in 4 university hospitals.
      Parasites were observed in 46,200 specimens. Of these cases, subjects with
      complete laboratory investigation (complete blood count - CBC, ferritin, total
      iron binding capacity - TIBC, and serum) and blastocystis hominis infection were
      included in this study as the case group. Of these cases, 6851 cases had only B.
      hominis infection. In the control group, 3615 subjects without parasite
      infestation were included. Age, haemoglobin (Hb), serum iron, TIBC, white blood
      cell (WBC), platelet (PLT), mean corpuscular volume (MCV), haematocrit (HCT) and
      erythrocyte sedimentation rate (ESR) were recorded for cases and controls. SPSS
      software version 13.0 was used for analysis. Independent sample t-test and chi(2)
      tests were used for comparison. RESULTS: Erythrocyte sedimentation rate level was
      significantly higher in cases with B. hominis infection (p < 0.05). C-reactive
      protein level was positive in 1.46% of cases and 0.5% of controls, which was
      statistically significant (p < 0.05). Frequency of serum iron < 120 was
      significantly higher in cases with B. hominis infection compared to controls.
      Occult blood was positive in 0.93% of cases and in none of the controls (p <
      0.05). CONCLUSIONS: The ESR, CRP and occult blood was significantly higher in
      cases with B. hominis infection.

PMID- 24868298
TI  - Treatment with ginkgo biloba extract protects rats against acute pancreatitis
      associated lung injury by modulating alveolar macrophage.
AB  - INTRODUCTION: Acute pancreatitis (AP) protease release induces lung parenchymal
      destruction via inflammatory mediators. Ginkgo biloba has been reported to have
      anti-inflammatory effects. AIM: To evaluate the effect of ginkgo biloba extract
      on experimental acute pancreatitis-associated lung injury in the rat and to
      investigate the underlying mechanisms. MATERIAL AND METHODS: Acute pancreatitis
      was induced in rats by injection of 5% sodium taurocholate into the biliary
      pancreatic duct. Ginkgo biloba extract (GBE) was administered and pancreas and
      lung injury were assessed by histological examination. Alveolar macrophages were
      harvested by bronchoalveolar lavage. Specificity fluorescent probe DAF-FM-DA was
      applied to observe nitric oxide (NO) bioavailability in alveolar macrophage. The
      expression of tumour necrosis factor alpha (TNF-alpha) and macrophage migration
      inhibitory factor (MIF) protein in alveolar macrophage was studied by ELISA.
      RESULTS: In sodium taurocholate-induced acute pancreatitis, treatment with GBE
      significantly protected rats against lung injury associated with pancreatitis in
      histological sections. Ginkgo biloba extract had a tendency to down-regulate NO
      bioavailability compared with the AP group, but without statistical significance.
      Moreover, TNF-alpha and MIF at protein levels in alveolar macrophage with GBE
      treatment were decreased compared with the AP group. CONCLUSIONS: These results
      suggest that GBE could effectively protect rats against acute pancreatitis
      associated lung injury. The GBE may inhibit excessive activation of alveolar
      macrophages from acute pancreatitis-associated lung injury through down
      regulation of generation of NO, TNF-alpha and MIF. These findings suggest that
      ginkgo biloba extract is a suitable candidate as an effective strategy against
      acute pancreatitis-associated lung injury.

PMID- 24868299
TI  - Functional dyspepsia symptom resolution after Helicobacter pylori eradication
      with two different regimens.
AB  - INTRODUCTION: Functional dyspepsia (FD), a common functional gastrointestinal
      disorder, has a complex underlying pathophysiological mechanism that involves
      changes in gastric motility, visceral hypersensitivity, genetic susceptibility,
      psychosocial factors and Helicobacter pylori infection. Although there are
      several H. pylori eradication treatments, there is not enough data that compare
      these different eradication treatments for FD symptom resolution. Most previous
      studies have focused on the eradication rates of H. pylori rather than symptom
      relief in FD. AIM: In this regard, we aimed to clarify if there is any difference
      between standard triple therapy and sequential therapy for symptom resolution of
      FD patients with H. pylori, using a validated health quality index. MATERIAL AND
      METHODS: A total of 194 patients were included in this study. The patients were
      randomly assigned to receive standard triple therapy (omeprazole, amoxicilline
      and clarithromycin for 14 days) or sequential therapy (omeprazole plus
      amoxicilline for 7 days and omeprazole twice daily, metronidazole and
      clarithromycin for a subsequent 7 days) by a blind physician for H. pylori
      status. Outcome measures were based on symptomatic improvement at 12 months using
      a validated measure of subjective well-being (Gastrointestinal Symptom Rating
      Scale - GSRS). RESULTS: We observed significant symptom resolution at 12 months
      in both treatment groups. On the other hand, there was no difference between the
      sequential or standard triple therapy groups regarding the alleviation of
      symptoms. CONCLUSIONS: No difference for symptom relief exists between sequential
      and triple therapy in patients with FD.

PMID- 24868300
TI  - Haemorrhage in the course of subcardial gastrointestinal stromal tumor - a case
      description.
AB  - This paper is a discussion of the case of a 51-year-old female patient admitted
      urgently for haemorrhage from the upper gastrointestinal tract and increased
      dysphagia. After preliminary treatment, the patient was qualified for surgery,
      during which a large lesion was discovered in the shape of a stromal tumor
      closely connected with the oesophago-gastric junction. A resection of the tumor
      and part of the oesophagus was carried out, and a cervical fistula was formed.
      After a 4-month period, the continuity of the gastrointestinal tract was restored
      by forming a substitute organ out of the ascending colon and the end of the small
      intestine, anastomosed on the cervix. The patient was discharged in good overall
      condition. 

PMID- 24868301
TI  - Hepatomegaly, weight loss and general malaise - the first manifestations of
      primary systemic amyloidosis.
AB  - Amyloidosis is characterised by the accumulation of poorly soluble fibrous
      proteins in the extracellular space of various bodily organs. Light chain
      amyloidosis (AL) is recognised as the most common form of systemic amyloidosis.
      Light chains are deposited in the majority of bodily organs, and accumulation of
      them in the liver produces hepatomegaly. We report a case of AL-systemic
      amyloidosis with liver involvement in a 71-year-old woman. Hepatomegaly, weight
      loss and general malaise were the first manifestations of the disease. Liver
      biopsy found amyloid deposits along the sinusoids as well as in the space of
      Disse, inside the vascular wall and in connective tissue of the portal tracts,
      which showed a positive reaction in Congo Red stain. Further diagnosis showed the
      presence of systemic amyloidosis. The patient was put on cyclophosphamide and
      steroid therapy. 

PMID- 24868302
TI  - USEFUL: Ultrasound Exam for Underlying Lesions incorporated into physical exam.
AB  - INTRODUCTION: The Ultrasound Screening Exam for Underlying Lesions (USEFUL) was
      developed in an attempt to establish a role for bedside ultrasound in the primary
      and preventive care setting. It is the purpose of our pilot study to determine if
      students were first capable of performing all of the various scans required of
      our USEFUL while defining such an ultrasound-assisted physical exam that would
      supplement the standard hands-on physical exam in the same head-to-toe structure.
      We also aimed to assess the time needed for an adequate exam and analyze if times
      improved with repetition and previous ultrasound training. METHODS: Medical
      students with ranging levels of ultrasound training received a 25-minute
      presentation on our USEFUL followed by a 30-minute hands-on session. Following
      the hands-on session, the students were asked to perform a timed USEFUL on 2-3
      standardized subjects. All images were documented as normal or abnormal with the
      understanding that an official detailed exam would be performed if an abnormality
      were to be found. All images were read and deemed adequate by board eligible
      emergency medicine ultrasound fellows. RESULTS: Twenty-six exams were performed
      by 9 students. The average time spent by all students per USEFUL was 11 minutes
      and 19 seconds. Students who had received the University of California, Irvine
      School of Medicine's integrated ultrasound curriculum performed the USEFUL
      significantly faster (p< 0.0025). The time it took to complete the USEFUL ranged
      from 6 minutes and 32 seconds to 17 minutes, and improvement was seen with each
      USEFUL performed. The average time to complete the USEFUL on the first
      standardized patient was 13 minutes and 20 seconds, while 11 minutes and 2
      seconds, and 9 minutes and 20 seconds were spent performing the exam on the
      second and third patient, respectively. CONCLUSION: Students were able to
      effectively complete all scans required by the USEFUL in a timely manner.
      Students who have been a part of the integrated ultrasound in medicine curriculum
      performed the USEFUL significantly faster than students who had not. Students
      were able to significantly improve upon the time it took them to complete the
      USEFUL with successive attempts. Future endpoints are aimed at assessing the
      feasibility and outcomes of an ultrasound-assisted physical exam in a primary
      care setting and the exam's effect on doctor-patient satisfaction. [West J Emerg
      Med. 2014;15(3):260-266.].

PMID- 24868303
TI  - Does prolonged length of stay in the emergency department affect outcome for
      stroke patients?
AB  - INTRODUCTION: Conflicting data exist regarding the association between the length
      of stay (LOS) of critically ill patients in the emergency department (ED) and
      their subsequent outcome. However, such patients are an overall heterogeneous
      group, and we therefore sought to study the association between EDLOS and
      outcomes in a specific subgroup of critically ill patients, namely those with
      acute ischemic stroke/transient ischemic attack (AIS/TIA). METHODS: This was a
      retrospective review of adult patients with a discharge diagnosis of AIS/TIA
      presenting to an ED between July 2009 and February 2010. We collected
      demographics, EDLOS, arrival stroke severity (National Institutes of Health
      Stroke Scale - NIHSS), intravenous tissue plasminogen activator (IV tPA) use,
      functional outcome at discharge, discharge destination and hospital-LOS. We
      analyzed relationship between EDLOS, outcomes and discharge destination after
      controlling for confounders. RESULTS: 190 patients were included in the cohort.
      Median EDLOS was 332 minutes (Inter-Quartile Range -IQR: 250.3-557.8). There was
      a significant inverse linear association between EDLOS and hospital-LOS
      (p=0.049). Patients who received IV tPA had a shorter median EDLOS (238 minutes,
      IQR: 194-299) than patients who did not (median: 387 minutes, IQR: 285-588
      minutes; p<0.0001). There was no significant association between EDLOS and poor
      outcome (p=0.40), discharge destination (p=0.20), or death (p=0.44). This
      remained true even after controlling for IV tPA use, NIHSS and hospital-LOS; and
      did not change even when analysis was restricted to AIS patients alone.
      CONCLUSION: There was no significant association between prolonged EDLOS and
      outcome for AIS/TIA patients at our institution. We therefore suggest that EDLOS
      alone is an insufficient indicator of stroke care in the ED, and that the ED can
      provide appropriate acute care for AIS/TIA patients. [West J Emerg Med.
      2014;15(3):267-275.].

PMID- 24868305
TI  - Skin infections and antibiotic stewardship: analysis of emergency department
      prescribing practices, 2007-2010.
AB  - INTRODUCTION: National guidelines suggest that most skin abscesses do not require
      antibiotics, and that cellulitis antibiotics should target streptococci, not
      community-associated MRSA (CA-MRSA). The objective of this study is to describe
      antimicrobial treatment of skin infections in U.S. emergency departments (EDs)
      and analyze potential quality measures. METHODS: The National Hospital Ambulatory
      Medical Care Survey (NHAMCS) is a 4-stage probability sample of all non-federal
      U.S. ED visits. In 2007 NHAMCS started recording whether incision and drainage
      was performed at ED visits. We conducted a retrospective analysis, pooling 2007
      2010 data, identified skin infections using diagnostic codes, and identified
      abscesses by performance of incision and drainage. We generated national
      estimates and 95% confidence intervals using weighted analyses; quantified
      frequencies and proportions; and evaluated antibiotic prescribing practices. We
      evaluated 4 parameters that might serve as quality measures of antibiotic
      stewardship, and present 2 of them as potentially robust enough for
      implementation. RESULTS: Of all ED visits, 3.2% (95% confidence interval 3.1
      3.4%) were for skin infection, and 2.7% (2.6-2.9%) were first visits for skin
      infection, with no increase over time (p=0.80). However, anti-CA-MRSA antibiotic
      use increased, from 61% (56-66%) to 74% (71-78%) of antibiotic regimens
      (p<0.001). Twenty-two percent of visits were for abscess, with a non-significant
      increase (p=0.06). Potential quality measures: Among discharged abscess patients,
      87% were prescribed antibiotics (84-90%, overuse). Among antibiotic regimens for
      abscess patients, 84% included anti-CA-MRSA agents (81-89%, underuse).
      CONCLUSION: From 2007-2010, use of anti-CA-MRSA agents for skin infections
      increased significantly, despite stable visit frequencies. Antibiotics were over
      used for discharged abscess cases, and CA-MRSA-active antibiotics were underused
      among regimens when antibiotics were used for abscess. [West J Emerg Med.
      2014;15(3):282-289.].

PMID- 24868304
TI  - Follow up for emergency department patients after intravenous contrast and risk
      of nephropathy.
AB  - INTRODUCTION: Contrast-induced nephropathy (CIN), defined as an increase in serum
      creatinine (SCr) greater than 25% or >=0.5 mg/dL within 3 days of intravenous
      (IV) contrast administration in the absence of an alternative cause, is the third
      most common cause of new acute renal failure in hospitalized patients. It is
      known to increase in-hospital mortality up to 27%. The purpose of this study was
      to investigate the rate of outpatient follow up and the occurrence of CIN in
      patients who presented to the emergency department (ED) and were discharged home
      after computed tomography (CT) of the abdomen and pelvis (AP) with IV contrast.
      METHODS: We conducted a single center retrospective review of charts for patients
      who required CT of AP with IV contrast and who were discharged home. Patients'
      clinical data included the presence of diabetes mellitus, hypertension, chronic
      kidney disease (CKD) and congestive heart failure (CHF). RESULTS: Five hundred
      and thirty six patients underwent CT of AP with IV contrast in 2011 and were
      discharged home. Diabetes mellitus was documented in 96 patients (18%).
      Hypertension was present in 141 patients (26.3%), and 82 patients (15.3%) were on
      angiotensin-converting-enzyme inhibitors (ACEI). Five patients (0.9%) had
      documented CHF and all of them were taking furosemide. Seventy patients (13%) had
      a baseline SCr >1.2 mg/dL. One hundred fifty patients (28%) followed up in one of
      the clinics or the ED within one week after discharge, but only 40 patients
      (7.5%) had laboratory workup. Out of 40 patients who followed up within 1 week
      after discharge, 9 patients (22.5%) developed CIN. One hundred ninety patients
      (35.4%) followed up in one of the clinics or the ED after 7 days and within 1
      month after discharge, but only 71 patients (13.2%) had laboratory workup
      completed. Out of 71 patients who followed up within 1 month, 11 patients (15%)
      developed CIN. The overall incidence of CIN was 15.3% (17 out of 111 patients).
      CONCLUSION: There was a poor outpatient follow up after CT of AP with IV contrast
      and biochemically CIN appears to be present in some patients. Unlike previous
      reports that CKD is the major risk factor for CIN, our results demonstrated that
      risk factors such as advanced age, DM and hypertension seem to predispose
      patients to CIN rather than abnormal baseline SCr. [West J Emerg Med.
      2014;15(3):276-281.].

PMID- 24868306
TI  - Survey of publications and the H-index of Academic Emergency Medicine Professors.
AB  - INTRODUCTION: The number of publications and how often these have been cited play
      a role in academic promotion. Bibliometrics that attempt to quantify the relative
      impact of scholarly work have been proposed. The h-index is defined as the number
      (h) of publications for an individual that have been cited at least h times. We
      calculated the h-index and number of publications for academic emergency
      physicians at the rank of professor. METHODS: We accessed the Society for
      Academic Emergency Medicine professor list in January of 2012. We calculated the
      number of publications through Web of Science and PubMed and the h-index using
      Google scholar and Web of Science. RESULTS: We identified 299 professors of
      emergency medicine. The number of professors per institution ranged from 1 to 13.
      Median h-index in Web of Science was 11 (interquartile range [IQR] 6-17, range 0
      51), in Google Scholar median h-index was 14 (IQR 9-22, range 0-63) The median
      number of publications reported in Web of Science was 36 (IQR 18-73, range 0-359.
      Total number of publications had a high correlation with the h-index (r=0.884).
      CONCLUSION: The h-index is only a partial measure of academic productivity. As a
      measure of the impact of an individual's publications it can provide a simple way
      to compare and measure academic progress and provide a metric that can be used
      when evaluating a person for academic promotion. Calculation of the h-index can
      provide a way to track academic progress and impact. [West J Emerg Med.
      2014;15(3):290-292.].

PMID- 24868307
TI  - Study of medical students' malpractice fear and defensive medicine: a "hidden
      curriculum?".
AB  - INTRODUCTION: Defensive medicine is a medical practice in which health care
      providers' primary intent is to avoid criticism and lawsuits, rather than
      providing for patients' medical needs. The purpose of this study was to
      characterize medical students' exposure to defensive medicine during medical
      school rotations. METHODS: We performed a cross-sectional survey study of medical
      students at the beginning of their third year. We gave students Likert scale
      questionnaires, and their responses were tabulated as a percent with 95%
      confidence interval (CI). RESULTS: Of the 124 eligible third-year students, 102
      (82%) responded. Most stated they rarely worried about being sued (85.3% [95%
      CI=77.1% to 90.9%]). A majority felt that faculty were concerned about
      malpractice (55.9% [95% CI=46.2% to 65.1%]), and a smaller percentage stated that
      faculty taught defensive medicine (32.4% [95% CI=24.1% to 41.9%]). Many students
      believed their satisfaction would be decreased by MC and lawsuits (51.0% [95%
      CI=41.4% to 60.5%]). Some believed their choice of medical specialty would be
      influenced by MC (21.6% [95% CI=14.7% to 30.5%]), and a modest number felt their
      enjoyment of learning medicine was lessened by MC (23.5% [95% CI=16.4% to
      32.6%]). Finally, a minority of students worried about practicing and learning
      procedures because of MC (16.7% [95% CI=10.7% to 25.1%]). CONCLUSION: Although
      third-year medical students have little concern about being sued, they are
      exposed to malpractice concerns and taught considerable defensive medicine from
      faculty. Most students believe that fear of lawsuits will decrease their future
      enjoyment of medicine. However, less than a quarter of students felt their
      specialty choice would be influenced by malpractice worries and that malpractice
      concerns lessened their enjoyment of learning medicine. [West J Emerg Med.
      2014;15(3):293-298.].

PMID- 24868308
TI  - Scholar quest: a residency research program aligned with faculty goals.
AB  - INTRODUCTION: The ACGME requires that residents perform scholarly activities
      prior to graduation, but this is difficult to complete and challenging to
      support. We describe a residency research program, taking advantage of
      environmental change aligning resident and faculty goals, to become a contributor
      to departmental cultural change and research development. METHODS: A research
      program, Scholar Quest (SQ), was developed as a part of an Information Mastery
      program. The goal of SQ is for residents to gain understanding of scholarly
      activity through a mentor-directed experience in original research. This
      curriculum is facilitated by providing residents protected time for didactics,
      seed grants and statistical/staff support. We evaluated total scholarly activity
      and resident/faculty involvement before and after implementation (PRE-SQ; 2003
      2005 and POST-SQ; 2007-2009). RESULTS: Scholarly activity was greater POST-SQ
      versus PRE-SQ (123 versus 27) (p<0.05) with an incidence rate ratio (IRR)=2.35.
      Resident and faculty involvement in scholarly activity also increased PRE-SQ to
      POST-SQ (22 to 98 residents; 10 to 39 faculty, p<0.05) with an IRR=2.87 and 2.69,
      respectively. CONCLUSION: Implementation of a program using department
      environmental change promoting a resident longitudinal research curriculum
      yielded increased resident and faculty scholarly involvement, as well as an
      increase in total scholarly activity. [West J Emerg Med. 2014;15(3):299-305.].

PMID- 24868309
TI  - Experience with emergency ultrasound training by Canadian emergency medicine
      residents.
AB  - INTRODUCTION: Starting in 2008, emergency ultrasound (EUS) was introduced as a
      core competency to the Royal College of Physicians and Surgeons of Canada (Royal
      College) emergency medicine (EM) training standards. The Royal College accredits
      postgraduate EM specialty training in Canada through 5-year residency programs.
      The objective of this study is to describe both the current experience with and
      the perceptions of EUS by Canadian Royal College EM senior residents. METHODS:
      This was a web-based survey conducted from January to March 2011 of all 39
      Canadian Royal College postgraduate fifth-year (PGY-5) EM residents. Main outcome
      measures were characteristics of EUS training and perceptions of EUS. RESULTS:
      Survey response rate was 95% (37/39). EUS was part of the formal residency
      curriculum for 86% of respondents (32/37). Residents most commonly received
      training in focused assessment with sonography for trauma, intrauterine
      pregnancy, abdominal aortic aneurysm, cardiac, and procedural guidance. Although
      the most commonly provided instructional material (86% [32/37]) was an ultrasound
      course, 73% (27/37) of residents used educational resources outside of residency
      training to supplement their ultrasound knowledge. Most residents (95% [35/37])
      made clinical decisions and patient dispositions based on their EUS
      interpretation without a consultative study by radiology. Residents had very
      favorable perceptions and opinions of EUS. CONCLUSION: EUS training in Royal
      College EM programs was prevalent and perceived favorably by residents, but there
      was heterogeneity in resident training and practice of EUS. This suggests
      variability in both the level and quality of EUS training in Canadian Royal
      College EM residency programs. [West J Emerg Med. 2014;15(3):306-311.].

PMID- 24868310
TI  - Assessment of the acute psychiatric patient in the emergency department: legal
      cases and caveats.

PMID- 24868311
TI  - Informed consent documentation for lumbar puncture in the emergency department.
AB  - INTRODUCTION: Informed consent is a required process for procedures performed in
      the emergency department (ED), though it is not clear how often or adequately it
      is obtained by emergency physicians. Incomplete performance and documentation of
      informed consent can lead to patient complaints, medico-legal risk, and
      inadequate education for the patient/guardian about the procedure. We undertook
      this study to quantify the incidence of informed consent documentation in the ED
      setting for lumbar puncture (LP) and to compare rates between pediatric (<18
      years) and adult patients. METHODS: In this retrospective cohort study, we
      reviewed the ED electronic health records (EHR) for all patients who underwent
      successful LPs in 3 EDs between April 2010 and June 2012. Specific elements of
      informed consent documentation were reviewed. These elements included the
      presence of general ED and LP-specific consent forms, signatures of
      patient/guardian, witness, and physician, documentation of purpose, risks,
      benefits, alternatives, and explanation of the LP. We also reviewed the use of
      educational material about the LP and LP-specific discharge information. RESULTS:
      Our cohort included 937 patients; 179 (19.1%) were pediatric. A signed general ED
      consent form was present in the EHR for 809 (86%) patients. A consent form for
      the LP was present for 524 (56%) patients, with signatures from 519 (99%)
      patients/guardians, 327 (62%) witnesses, and 349 (67%) physicians. Documentation
      rates in the EHR were as follows: purpose (698; 74%), risks (742; 79%), benefits
      (605; 65%), alternatives (635; 68%), and explanation for the LP (57; 6%).
      Educational material about the LP was not documented as having been given to any
      of the patients and LP-specific discharge information was documented as given to
      21 (2%) patients. No significant differences were observed in the documentation
      of informed consent elements between pediatric and adult patients. CONCLUSION:
      General ED consent was obtained in the vast majority of patients, but use of a
      specific LP consent form and documentation of the elements of informed consent
      for LP in the ED were suboptimal, though comparable between pediatric and adult
      patients. There is significant opportunity for improvement in many aspects of
      documenting informed consent for LP in the ED. [West J Emerg Med. 2014;15(3):318
      324.].

PMID- 24868312
TI  - Depression is associated with repeat emergency department visits in patients with
      non-specific abdominal pain.
AB  - INTRODUCTION: Patients with abdominal pain often return multiple times despite no
      definitive diagnosis. Our objective was to determine if repeat emergency
      department (ED) use among patients with non-specific abdominal pain might be
      associated with a diagnosis of moderate to severe depressive disorder. METHODS:
      We screened 987 ED patients for major depression during weekday daytime hours
      from June 2011 through November 2011 using a validated depression screening tool,
      the PHQ-9. Each subject was classified as either no depression, mild depression
      or moderate/severe depression based on the screening tool. Within this group, we
      identified 83 patients with non-specific abdominal pain by either primary or
      secondary diagnosis. Comparing depressed patients versus non-depressed patients,
      we analyzed demographic characteristics and number of prior ED visits in the past
      year. RESULTS: In patients with non-specific abdominal pain, 61.9% of patients
      with moderate or severe depression (PHQ9>=10) had at least one visit to our ED
      for the same complaint within a 365-day period, as compared to 29.2% of patients
      with no depression (PHQ9<5), (p=0.013). CONCLUSION: Repeat ED use among patients
      with non-specific abdominal pain is associated with moderate to severe depressive
      disorder. Patients with multiple visits for abdominal pain may benefit from
      targeted ED screening for depression. [West J Emerg Med. 2014;15(3):325-328.].

PMID- 24868313
TI  - Epidemiology of the Systemic Inflammatory Response Syndrome (SIRS) in the
      emergency department.
AB  - INTRODUCTION: Consensus guidelines recommend sepsis screening for adults with
      systemic inflammatory response syndrome (SIRS), but the epidemiology of SIRS
      among adult emergency department (ED) patients is poorly understood. Recent
      emphasis on cost-effective, outcomes-based healthcare prompts the evaluation of
      the performance of large-scale efforts such as sepsis screening. We studied a
      nationally representative sample to clarify the epidemiology of SIRS in the ED
      and subsequent category of illness. METHODS: This was a retrospective analysis of
      ED visits by adults from 2007 to 2010 in the National Hospital Ambulatory Medical
      Care Survey (NHAMCS). We estimated the incidence of SIRS using initial ED vital
      signs and a Bayesian construct to estimate white blood cell count based on test
      ordering. We report estimates with Bayesian modified credible intervals (mCIs).
      RESULTS: We used 103,701 raw patient encounters in NHAMCS to estimate 372,844,465
      ED visits over the 4-year period. The moderate estimate of SIRS in the ED was
      17.8% (95% mCI: 9.7 to 26%). This yields a national moderate estimate of
      approximately 16.6 million adult ED visits with SIRS per year. Adults with and
      without SIRS had similar demographic characteristics, but those with SIRS were
      more likely to be categorized as emergent in triage (17.7% versus 9.9%, p<0.001),
      stay longer in the ED (210 minutes versus 153 minutes, p<0.0001), and were more
      likely to be admitted (31.5% versus 12.5%, p<0.0001). Infection accounted for
      only 26% of SIRS patients. Traumatic causes of SIRS comprised 10% of
      presentations; other traditional categories of SIRS were rare. CONCLUSION: SIRS
      is very common in the ED. Infectious etiologies make up only a quarter of adult
      SIRS cases. SIRS may be more useful if modified by clinician judgment when used
      as a screening test in the rapid identification and assessment of patients with
      the potential for sepsis. [West J Emerg Med. 2014;15(3):329-336.].

PMID- 24868315
TI  - Lentivirus-mediated Nox4 shRNA invasion and angiogenesis and enhances
      radiosensitivity in human glioblastoma.
AB  - Radioresistance remains a significant therapeutic obstacle in glioblastoma.
      Reactive oxygen species (ROS) are associated with multiple cellular functions
      such as cell proliferation and apoptosis. Nox4 NADPH oxidase is abundantly
      expressed and has proven to be a major source of ROS production in glioblastoma.
      Here we investigated the effects of Nox4 on GBM tumor cell invasion,
      angiogenesis, and radiosensitivity. A lentiviral shRNA vector was utilized to
      stably knockdown Nox4 in U87MG and U251 glioblastoma cells. ROS production was
      measured by flow cytometry using the fluorescent probe DCFH-DA. Radiosensitivity
      was evaluated by clonogenic assay and survival curve was generated. Cell
      proliferation activity was assessed by a cell counting proliferation assay and
      invasion/migration potential by Matrigel invasion assay. Tube-like structure
      formation assay was used to evaluate angiogenesis ability in vitro and VEGF
      expression was assessed by MTT assay. Nox4 knockdown reduced ROS production
      significantly and suppressed glioblastoma cells proliferation and invasion and
      tumor associated angiogenesis and increased their radiosensitivity in vitro. Our
      results indicate that Nox4 may play a crucial role in tumor invasion,
      angiogenesis, and radioresistance in glioblastoma. Inhibition of Nox4 by
      lentivirus-mediated shRNA could be a strategy to overcome radioresistance and
      then improve its therapeutic efficacy for glioblastoma. 

PMID- 24868314
TI  - Isoprostanes and neuroprostanes as biomarkers of oxidative stress in
      neurodegenerative diseases.
AB  - Accumulating data shows that oxidative stress plays a crucial role in
      neurodegenerative disorders. The literature data indicate that in vivo or
      postmortem cerebrospinal fluid and brain tissue levels of F2-isoprostanes (F2
      IsoPs) especially F4-neuroprotanes (F4-NPs) are significantly increased in some
      neurodegenerative diseases: multiple sclerosis, Alzheimer's disease, Huntington's
      disease, and Creutzfeldt-Jakob disease. Central nervous system is the most
      metabolically active organ of the body characterized by high requirement for
      oxygen and relatively low antioxidative activity, what makes neurons and glia
      highly susceptible to destruction by reactive oxygen/nitrogen species and
      neurodegeneration. The discovery of F2-IsoPs and F4-NPs as markers of lipid
      peroxidation caused by the free radicals has opened up new areas of investigation
      regarding the role of oxidative stress in the pathogenesis of human
      neurodegenerative diseases. This review focuses on the relationship between F2
      IsoPs and F4-NPs as biomarkers of oxidative stress and neurodegenerative
      diseases. We summarize the knowledge of these novel biomarkers of oxidative
      stress and the advantages of monitoring their formation to better define the
      involvement of oxidative stress in neurological diseases. 

PMID- 24868317
TI  - Curcumin inhibits mitochondrial injury and apoptosis from the early stage in EAE
      mice.
AB  - The exact pathophysiological change concerning mitochondrial injury and
      oligodendrocyte apoptosis in MS and EAE model is still unknown. Whether curcumin
      is able to inhibit mitochondrial injury and suppress the apoptosis in the early
      stages of MS/EAE is still unclear. We first explored mitochondrial injury and
      apoptosis at different time points p.i. in C57 BL/6 EAE mice. We then explored
      the effects of curcumin on mitochondria and apoptosis. Results showed that
      mitochondrial injury can be observed 3 days p.i. Apoptosis in the spinal cord
      occurred 3 days p.i. and the apoptotic cells were shown to be oligodendrocytes
      and neuronal cells. Curcumin significantly reduced the number of apoptotic cells
      and inhibited the upregulation of cyt-c, caspase-9, and caspase-3 at 7 days p.i.
      in the EAE mice. These observations demonstrate that mitochondrial injury and
      oligodendrocyte/neuronal apoptosis occur in the early stages of EAE. Curcumin can
      inhibit apoptosis in EAE mice which maybe act through protection of mitochondrial
      injury and inhibition of the intrinsic apoptotic pathway. 

PMID- 24868316
TI  - Leucocyte telomere shortening in relation to newly diagnosed type 2 diabetic
      patients with depression.
AB  - The goal of this study is to investigate the association between oxidative stress
      and telomere length shortening in the comorbid depression and diabetes.
      Therefore, 71 patients with newly diagnosed type 2 diabetes (T2D) and 52 subjects
      with normal glycemic level (control, Ctrl) were enrolled. Depressive status was
      identified with the Depression Subscale of Hospital Anxiety and Depression Scale
      (HADS-D). Leukocyte telomere length ratio (T/S ratio) was determined with
      quantitative PCR. Oxidative stress status was evaluated with 8-hydroxy
      desoxyguanosine (8-OHdG) assay kit. Some other biochemical blood testing was also
      performed. The data showed that T2D patients had higher proportion of depression
      evaluated by the HADS-D (x(2) = 4.196, P = 0.041). T/S ratio was significantly
      negatively correlated with 8-OHdG, HADS-D, age, HbA1c, FPG, and HOMA-IR. In
      addition, HADS-D was significantly positively correlated with HbA1c, FPG, HOMA
      IR, and 8-OHdG. Both HADS-D and 8-OHdG were the major independent predictors for
      T/S ratio. This study indicates that oxidative stress contributes to both
      telomere length shortening and depression development in newly diagnosed type 2
      diabetic patients, while in depression status, some other mechanisms besides
      oxidative stress may also affect the telomere length.

PMID- 24868318
TI  - Lipid peroxidation in psychiatric illness: overview of clinical evidence.
AB  - The brain is known to be sensitive to oxidative stress and lipid peroxidation.
      While lipid peroxidation has been shown to contribute to many disease processes,
      its role in psychiatric illness has not been investigated until recently. In this
      paper, we provide an overview of lipid peroxidation in the central nervous system
      as well as clinical data supporting a link between lipid peroxidation and
      disorders such as schizophrenia, bipolar disorder, and major depressive disorder.
      These data support further investigation of lipid peroxidation in the effort to
      uncover therapeutic targets and biomarkers of psychiatric disease. 

PMID- 24868319
TI  - Salidroside stimulates mitochondrial biogenesis and protects against H2O2-induced
      endothelial dysfunction.
AB  - Salidroside (SAL) is an active component of Rhodiola rosea with documented
      antioxidative properties. The purpose of this study is to explore the mechanism
      of the protective effect of SAL on hydrogen peroxide- (H2O2-) induced endothelial
      dysfunction. Pretreatment of the human umbilical vein endothelial cells (HUVECs)
      with SAL significantly reduced the cytotoxicity brought by H2O2. Functional
      studies on the rat aortas found that SAL rescued the endothelium-dependent
      relaxation and reduced superoxide anion (O2(?-)) production induced by H2O2.
      Meanwhile, SAL pretreatment inhibited H2O2-induced nitric oxide (NO) production.
      The underlying mechanisms involve the inhibition of H2O2-induced activation of
      endothelial nitric oxide synthase (eNOS), adenosine monophosphate-activated
      protein kinase (AMPK), and Akt, as well as the redox sensitive transcription
      factor, NF-kappa B (NF- kappa B). SAL also increased mitochondrial mass and
      upregulated the mitochondrial biogenesis factors, peroxisome proliferator
      activated receptor gamma-coactivator-1alpha (PGC-1 alpha ), and mitochondrial
      transcription factor A (TFAM) in the endothelial cells. H2O2-induced
      mitochondrial dysfunction, as demonstrated by reduced mitochondrial membrane
      potential (Delta psi m) and ATP production, was rescued by SAL pretreatment.
      Taken together, these findings implicate that SAL could protect endothelium
      against H2O2-induced injury via promoting mitochondrial biogenesis and function,
      thus preventing the overactivation of oxidative stress-related downstream
      signaling pathways. 

PMID- 24868320
TI  - Obesity and non-alcoholic fatty liver disease: Disparate associations among Asian
      populations.
AB  - Obesity is a global epidemic contributing to an increasing prevalence of obesity
      related systemic disorders, including nonalcoholic fatty liver disease. The
      rising prevalence of nonalcoholic steatohepatitis (NASH) will in the near future
      lead to end-stage liver disease in a large cohort of patients with NASH-related
      cirrhosis and NASH is predicted to be a leading indication for liver
      transplantation in the coming decade. However, the prevalence of obesity and the
      progression of hepatic histological damage associated with NASH exhibit
      significant ethnic disparities. Despite a significantly lower body mass index and
      lower rates of obesity compared to other ethnic groups, Asians continue to
      demonstrate a significant prevalence of hypertension, diabetes, metabolic
      syndrome and NASH. Ethnic disparities in central adiposity and visceral fat
      distribution have been hypothesized to contribute to these ethnic disparities.
      The current review focuses on the epidemiology of obesity and NASH among Asian
      populations. 

PMID- 24868321
TI  - Gender and racial differences in nonalcoholic fatty liver disease.
AB  - Due to the worldwide epidemic of obesity, nonalcoholic fatty liver disease
      (NAFLD) has become the most common cause of elevated liver enzymes. NAFLD
      represents a spectrum of liver injury ranging from simple steatosis to
      nonalcoholic steatohepatitis (NASH) which may progress to advanced fibrosis and
      cirrhosis. Individuals with NAFLD, especially those with metabolic syndrome, have
      higher overall mortality, cardiovascular mortality, and liver-related mortality
      compared with the general population. According to the population-based studies,
      NAFLD and NASH are more prevalent in males and in Hispanics. Both the gender and
      racial ethnic differences in NAFLD and NASH are likely attributed to interaction
      between environmental, behavioral, and genetic factors. Using genome-wide
      association studies, several genetic variants have been identified to be
      associated with NAFLD/NASH. However, these variants account for only a small
      amount of variation in hepatic steatosis among ethnic groups and may serve as
      modifiers of the natural history of NAFLD. Alternatively, these variants may not
      be the causative variants but simply markers representing a larger body of
      genetic variations. In this article, we provide a concise review of the gender
      and racial differences in the prevalence of NAFLD and NASH in adults. We also
      discuss the possible mechanisms for these disparities. 

PMID- 24868322
TI  - Chronic hepatitis B: Advances in treatment.
AB  - Treatment of chronic hepatitis B (CHB) has markedly improved in the last 15 years
      due to the availability of direct antivirals which greatly increase therapeutic
      options. Currently, there are two classes of agents licensed for CHB treatment:
      standard or pegylated interferon alpha (IFN or Peg-IFN) and five
      nucleoside/nucleotide analogues (NAs). Long-term treatment with NAs is the
      treatment option most often used in the majority of CHB patients. Entecavir and
      tenofovir, the most potent NAs with high barrier to resistance, are recommended
      as first-line monotherapy by all major treatment guidelines and can lead to long
      lasting virological suppression, resulting in histological improvement or
      reversal of advanced fibrosis and reduction in disease progression and liver
      related complications. In this review, we focus on current treatment strategies
      of chronic hepatitis B and discuss the most recent efficacy and safety data from
      clinical trials and real life clinical practice. Recent findings of response
      guided approaches are also discussed. 

PMID- 24868324
TI  - Metabolic syndrome and non-alcoholic fatty liver disease in liver surgery: The
      new scourges?
AB  - The aim of this topic highlight is to review relevant evidence regarding the
      influence of the metabolic syndrome (MS) and its associated liver manifestation,
      non-alcoholic fatty liver disease (NAFLD), on the development of liver cancer as
      well as their impact on the results of major liver surgery. MS and NAFLD, whose
      incidences are significantly increasing in Western countries, are leading to a
      changing profile of the patients undergoing liver surgery. A MEDLINE search was
      performed for relevant articles using the key words "metabolic syndrome", "liver
      resection", "liver transplantation", "non alcoholic fatty liver disease", "non
      alcoholic steatohepatitis" and "liver cancer". On one hand, the MS favors the
      development of primary liver malignancies (hepatocellular carcinoma and
      cholangiocarcinoma) either through NAFLD liver parenchymal alterations
      (steatosis, steatohepatitis, fibrosis) or in the absence of significant
      underlying liver parenchyma changes. Also, the existence of NAFLD may have a
      specific impact on colorectal liver metastases recurrence. On the other hand, the
      postoperative period following partial liver resection and liver transplantation
      is at increased risk of both postoperative complications and mortality. These
      deleterious effects seem to be related to the existence of liver specific
      complications but also higher cardio-vascular sensitivity in a setting of
      MS/NAFLD. Finally, the long-term prognosis after curative surgery joins that of
      patients operated on with other types of underlying liver diseases. An increased
      rate of patients with MS/NAFLD referred to hepatobiliary units has to be
      expected. The higher operative risk observed in this subset of patients will
      require specific improvements in their perioperative management. 

PMID- 24868323
TI  - Cystic echinococcosis of the liver: A primer for hepatologists.
AB  - Cystic echinococcosis (CE) is a complex, chronic and neglected disease with a
      worldwide distribution. The liver is the most frequent location of parasitic
      cysts. In humans, its clinical spectrum ranges from asymptomatic infection to
      severe, potentially fatal disease. Four approaches exist in the clinical
      management of CE: surgery, percutaneous techniques and drug treatment for active
      cysts, and the "watch and wait" approach for inactive cysts. Allocation of
      patients to these treatments should be based on cyst stage, size and location,
      available clinical expertise, and comorbidities. However, clinical decision
      algorithms, efficacy, relapse rates, and costs have never been properly
      evaluated. This paper reviews recent advances in classification and diagnosis and
      the currently available evidence for clinical decision-making in cystic
      echinococcosis of the liver. 

PMID- 24868326
TI  - NS3 protease inhibitors for treatment of chronic hepatitis C: Efficacy and
      safety.
AB  - A new treatment paradigm for hepatitis C is that the treatment must include an
      existing direct-acting antiviral agent, namely, a protease inhibitor (PI)
      combined with PEGylated interferon-alpha and ribavirin. The currently marketed
      PIs and PIs in clinical trials have different mechanisms of action. The
      development of new PIs aims for an improved safety profile and higher
      effectiveness. This article reviews NS3/4A protease inhibitors, focusing on major
      criteria such as their effectiveness and safety. Specific attention is paid to
      dosing regimens and adverse event profiles of PIs administered in clinical
      settings. 

PMID- 24868327
TI  - CYP2E1 immunoglobulin G4 subclass antibodies after desflurane anesthesia.
AB  - AIM: To investigate CYP2E1 IgG4 autoantibody levels and liver biochemical markers
      in adult patients after anesthesia with desflurane. METHODS: Forty patients who
      were > 18 years old and undergoing elective surgery under general anesthesia with
      desflurane were studied. Alpha-glutathione-S-transferase (alphaGST) and IgG4
      antibodies against CYP2E1 were measured preoperatively and 96 h postoperatively,
      as well as complete blood count, prothrombin time (PT), activated partial
      thromboplastin time (aPTT), international normalized ratio (INR), aspartate
      aminotransferase (SGOT), alanine aminotransferase (SGPT), g-glutamyl
      transpeptidase (gGT), alkaline phosphatase, total serum proteins, albumin and
      bilirubin. A separate group of 8 patients who received regional anesthesia was
      also studied for calibration of the methodology used for CYP2E1 IgG4 and alphaGST
      measurements. Student's t-test and the Mann-Whitney U test were used for
      comparison of the continuous variables, and Fisher's exact test was used for the
      categorical variables. All tests were two-tailed, with statistical significance
      set as P < 0.05. RESULTS: None of the patients developed postoperative liver
      dysfunction, and all patients were successfully discharged from the hospital. No
      statistically significant difference was observed regarding liver function tests
      (SGOT, SGPT, gammaGT, bilirubin, INR), alphaGST and CYP2E1 IgG4, before and after
      exposure to desflurane. After dividing patients into two subgroups based on
      whether or not they had received general anesthesia in the past, no significant
      difference in the levels of CYP2E1 IgG4 was observed at baseline or 96 h after
      desflurane administration (P = 0.099 and P = 0.051, respectively). Alpha-GST
      baseline levels and levels after the intervention also did not differ
      significantly between these two subgroups (P > 0.1). The mean alphaGST
      differences were statistically elevated in men by 2.15 ng/mL compared to women
      when adjusted for BMI, duration of anesthesia, number of times anesthesia was
      administered previously and length of hospital stay. No significant difference
      was observed between patients who received desflurane and those who received
      regional anesthesia at any time point. CONCLUSION: There was no difference in
      CYP2E1 IgG4 or alphaGST levels after desflurane exposure; further research is
      required to investigate their role in desflurane-induced liver injury.

PMID- 24868325
TI  - MUanagement of patients with hepatitis B and C before and after liver and kidney
      transplantation.
AB  - New nucleos(t)ide analogues (NAs) with high genetic barrier to hepatitis B virus
      (HBV) resistance (such as entecavir, tenofovir) have improved the prognosis of
      patients with HBV decompensated cirrhosis and have prevented HBV recurrence after
      liver transplantation (LT). NAs are considered the most proper approach for HBV
      infection in patients under renal replacement therapy but their doses should be
      adjusted according to the patient's creatinine clearance. In addition, physicians
      should be aware of the potential nephrotoxicity. However, patients with chronic
      hepatitis C and decompensated cirrhosis can receive only one therapeutic option
      before LT, as well as for Hepatitis C virus (HCV) recurrence after LT, which is
      the combination of subcutaneous Peg-IFN and ribavirin. Generally, therapy for HCV
      after renal transplantation should be avoided. Although the optimal antiviral
      therapy for HCV infection has not been established, attention has turned to a
      new, oral direct acting antiviral treatment which marks a promising strategy in
      prognosis and in amelioration of these diseases. 

PMID- 24868328
TI  - Central hepatectomy for centrally located malignant liver tumors: A systematic
      review.
AB  - AIM: To study whether central hepatectomy (CH) can achieve similar overall
      patient survival and disease-free survival rates as conventional major
      hepatectomies or not. METHODS: A systematic literature search was performed in
      MEDLINE for articles published from January 1983 to June 2013 to evaluate the
      evidence for and against CH in the management of central hepatic malignancies and
      to compare the perioperative variables and outcomes of CH to lobar/extended
      hemihepatectomy. RESULTS: A total of 895 patients were included from 21 relevant
      studies. Most of these patients who underwent CH were a sub-cohort of larger
      liver resection studies. Only 4 studies directly compared Central vs hemi
      /extended hepatectomies. The range of operative time for CH was reported to be
      115 to 627 min and Pringle's maneuver was used for vascular control in the
      majority of studies. The mean intraoperative blood loss during CH ranged from 380
      to 2450 mL. The reported morbidity rates ranged from 5.1% to 61.1%, the most
      common surgical complication was bile leakage and the most common cause of
      mortality was liver failure. Mortality ranged from 0.0% to 7.1% with an overall
      mortality of 2.3% following CH. The 1-year overall survival (OS) for patients
      underwent CH for hepatocellular carcinoma ranged from 67% to 94%; with the 3-year
      and 5-year OS having a reported range of 44% to 66.8%, and 31.7% to 66.8%
      respectively. CONCLUSION: Based on current literature, CH is a promising option
      for anatomical parenchymal-preserving procedure in patients with centrally
      located liver malignancies; it appears to be safe and comparable in both
      perioperative, early and long term outcomes when compared to patients undergoing
      hemi-/extended hepatectomy. More prospective studies are awaited to further
      define its role.

PMID- 24868329
TI  - Ductal paucity and Warkany syndrome in a patient with congenital extrahepatic
      portocaval shunt.
AB  - An eleven-year-old clinically dysmorphic and developmentally retarded male child
      presenting with complaints of 5 episodes of recurrent cholestatic jaundice since
      3 years of age was evaluated. Imaging revealed features consistent with
      congenital extrahepatic portocaval shunt (Abernethy type 1b), multiple
      regenerative liver nodules and intrahepatic biliary radical dilatation. The
      presence of ductal paucity and trisomy 8 were confirmed on liver biopsy and
      karyotyping. The explanation for unusual and previously unreported features in
      the present case has been proposed. 

PMID- 24868330
TI  - Rare cause of abdominal incidentaloma: Hepatoduodenal ligament teratoma.
AB  - The occurrence of a hepatoduodenal ligament teratoma is extremely rare, with only
      a few cases reported in the literature. This case report describes the discovery
      of a hepatoduodenal ligament lesion revealed during abdominal ultrasonography for
      cholelithiasis-related abdominal pain in a 27-year-old female. Cross-sectional
      imaging identified a 5 cm * 4 cm heterogeneous mass of fat tissue with irregular
      calcification located in the posterior-superior aspect of the head of the
      pancreas. An encapsulated lesion showing no invasion to the common bile duct or
      adjacent organs and vessels was exposed during laparotomy and resected.
      Intraoperative cholangiography during the cholecystectomy showed no
      abnormalities. The postoperative course was uneventful. Pathological analysis of
      the resected mass indicated hepatoduodenal ligament teratoma. This case report
      demonstrates that cross-sectional imaging, such as computed tomography, can
      reveal suspected incidences of this rare type of teratoma, which can then be
      confirmed after pathologic analysis of the specimen. The prognosis after complete
      surgical resection of lesions presenting with benign pathological features is
      excellent. 

PMID- 24868331
TI  - Single-incision laparoscopic cecectomy for low-grade appendiceal mucinous
      neoplasm after laparoscopic rectectomy.
AB  - In this case report, we discuss single-incision laparoscopic cecectomy for low
      grade appendiceal neoplasm after laparoscopic anterior resection for rectal
      cancer. The optimal surgical therapy for low-grade appendiceal neoplasm is
      controversial; currently, the options include appendectomy, cecectomy, right
      hemicolectomy, and open or laparoscopic surgery. Due to the risk of pseudomyxoma
      peritonei, complete resection without rupture is necessary. We have encountered 5
      cases of low-grade appendiceal neoplasm and all 5 patients had no lymph node
      metastasis. We chose the appendectomy or cecectomy without lymph node dissection
      if preoperative imaging studies did not suspect malignancy. In the present case,
      we performed cecectomy without lymph node dissection by single-incision
      laparoscopic surgery (SILS), which is reported to be a reduced port surgery
      associated with decreased invasiveness and patient stress compared with
      conventional laparoscopic surgery. We are confident that SILS is a feasible
      alternative to traditional surgical procedures for borderline tumors, such as low
      grade appendiceal neoplasms. 

PMID- 24868332
TI  - Penile low-intensity shock wave therapy: a promising novel modality for erectile
      dysfunction.
AB  - Penile extracorporeal low-intensity shock wave therapy (LIST) to the penis has
      recently emerged as a novel and promising modality in the treatment of erectile
      dysfunction (ED). LIST has angiogenic properties and stimulates
      neovascularization. If applied to the corpora cavernosa, LIST can improve penile
      blood flow and endothelial function. In a series of clinical trials, including
      randomized double-blind sham-controlled studies, LIST has been shown to have a
      substantial effect on penile hemodynamics and erectile function in patients with
      vasculogenic ED. LIST is effective in patients who are responsive to
      phosphodiesterase 5 inhibitors (PDE5i) and can also convert PDE5i nonresponders
      to responders. The response to LIST wanes gradually over time, and after 2 years,
      about half of the patients maintain their function. Extensive research is needed
      to understand the effect of LIST on erectile tissue, to modify the treatment
      protocol to maximize its outcomes, and to identify the patients who will benefit
      the most from this treatment. 

PMID- 24868333
TI  - Epidemiology of lower urinary tract symptoms: emphasis on the status in Korea.
AB  - A comprehensive and correct understanding of epidemiologic finding about lower
      urinary tract symptoms (LUTS) is important for several reasons. First, LUTS are
      highly prevalent in both genders all around the world and are expected to be a
      major concern to physicians in the near future because of the rapid rise in the
      elderly population. Second, it is crucial to observe trends in prevalence when
      national health care policy is established. By using a Medline search with
      various terms related to LUTS and prevalence, a review of epidemiologic studies
      was undertaken with an emphasis on the status in Korea. Despite the suggestions
      made by the International Continence Society, the lack of uniform definitions and
      the lack of a unified threshold of symptoms are the biggest obstacles in
      epidemiologic study with regard to LUTS. Most Korean epidemiologic studies on
      LUTS have been reported since 2000 and reveal that the prevalences of specific
      clinical conditions, such as LUTS, benign prostatic hyperplasia, overactive
      bladder, and detrusor underactivity, are in line with prevalences in Western
      counties. However, the prevalence of nocturia is somewhat different from that in
      Western countries. Many epidemiologic studies of LUTS have provided us with
      valuable information and a better understanding of the clinical conditions. Given
      that the impact of these clinical conditions on quality of life and health care
      cost will be emphasized more in the near future, more studies on optimal
      management approaches to LUTS are needed on the basis of this knowledge. 

PMID- 24868334
TI  - Pulmonary metastases after low-dose-rate brachytherapy for localized prostate
      cancer.
AB  - PURPOSE: To analyze unusual events and focus discussion on pulmonary metastasis
      in particular after low-dose-rate brachytherapy (LDR-BT) for prostate cancer
      (PCa). MATERIALS AND METHODS: A total of 616 consecutive patients who had
      undergone LDR-BT for clinically localized PCa at Jikei University Hospital
      between October 2003 and April 2010 were enrolled in this study. Follow-up
      information was summarized, and patterns of biochemical recurrence and clinical
      outcome were investigated. RESULTS: Disease risk was stratified as low-risk in
      231 patients, intermediate-risk in 365, and high-risk in 20, respectively. Of
      these patients, 269 (43.7%) had received hormonal therapy (HT) in combination
      with LDR-BT, and 80 (13.0%) had received external beam radiotherapy (EBRT).
      Average dosimetric parameter values with and without EBRT were 95.3% and 94.2%
      for V100, 132.8 Gy and 164.2 Gy for D90, and 180.6 Gy2 and 173.7 Gy2 for the
      biologically effective dose. Biochemical recurrence was noted in 14 patients
      (6.1%) in the low-risk group, 25 patients (6.8%) in the intermediate-risk group,
      and 6 patients (30.0%) in the high-risk group, respectively. In these cases of
      biochemical recurrence, 9 (64.3%), 13 (52.0%), and 4 patients (66.7%) in each
      respective risk group showed signs of clinical recurrence. Five patients (19.2%)
      with clinical recurrence developed pulmonary metastases, of which 4 were isolated
      lesions. All tumors responded favorably to subsequent HT. CONCLUSIONS: LDR-BT for
      biologically aggressive PCa may be linked to possible pulmonary metastasis owing
      to tumor dissemination during seed implantation. This information is important in
      planning adequate treatment for these patients.

PMID- 24868335
TI  - Efficacy of Bicalutamide 150-mg Monotherapy Compared With Combined Androgen
      Blockade in Patients With Locally Advanced Prostate Cancer.
AB  - PURPOSE: We compared the efficacy, survival rate, and adverse events between
      bicalutamide 150-mg monotherapy and combined androgen blockade (CAB) in men with
      locally advanced prostate cancer. MATERIALS AND METHODS: From March 2003 to July
      2012, we retrospectively included 74 patients who were treated for more than 3
      months and were followed up for more than 6 months. 25 men were treated with
      bicalutamide 150-mg only (group 1) and 49 men received CAB (group 2). Serum
      prostate-specific antigen (PSA) change, survival rate, and adverse events were
      compared between the 2 groups. RESULTS: The PSA levels before and after treatment
      were 37.0+/-32.8 ng/mL and 9.5+/-27.0 ng/mL in group 1 (p<0.001) and 50.2+/-40.0
      ng/mL and 20.0+/-35.8 ng/mL in group 2 (p<0.001). Mean survival rates were 78.9%
      in group 1 and 52.3% in group 2 (p=0.055). There were no statistically
      significant differences in adverse events between the 2 groups (p=0.304). The
      International Index of Erectile Function 5 (IIEF-5) score before treatment was
      19.3+/-5.9 in group 1 and 18.3+/-5.8 in group 2 (p=0.487). The IIEF-5 score after
      treatment was 17.1+/-6.3 in group 1 and 14.0+/-6.1 in group 2, which was a
      statistically significant difference (p=0.036). CONCLUSIONS: The PSA change, mean
      survival rate, and adverse events in patients with locally advanced prostate
      cancer treated with bicalutamide 150-mg and CAB did not differ significantly.
      However, sexual function was better in the bicalutamide 150-mg group. Therefore,
      bicalutamide 150-mg monotherapy could be considered as a treatment for locally
      advanced prostate cancer in patients concerned about sexual function.

PMID- 24868336
TI  - Predictive value of the cancer of the prostate risk assessment score for
      recurrence-free survival after radical prostatectomy in Korea: a single-surgeon
      series.
AB  - PURPOSE: To evaluate the validity of the cancer of the prostate risk assessment
      (CAPRA) score, a newly developed nomogram for preoperative prediction of
      recurrence after radical prostatectomy, in a single institution in Korea.
      MATERIALS AND METHODS: We retrospectively studied 115 men who had undergone
      radical prostatectomy as the first treatment for localized prostate cancer. The
      validity of the CAPRA score for the prediction of recurrence-free survival (RFS)
      and pathologic outcome was evaluated by using Kaplan-Meier analysis and a
      proportional hazards regression model. A seven-group model and a three-group
      model were used for the results. RESULTS: None of the variables of the CAPRA
      score was favorable compared with the previously reported data. The three-group
      model was significantly related with 3- and 5-year RFS (p<0.05), but the seven
      group model was not. The concordance indices of the CAPRA score were 0.74 and
      0.77. Of four components excluding the clinical T stage, three independently
      predicted RFS (age, Gleason sum, and percentage of positive biopsies). The CAPRA
      score was significantly related to the margin status, extracapsular extension,
      and seminal vesicle invasion in both the seven- and three-group models. In the
      three-group model, pathologic outcomes were more strongly related, especially a
      higher risk of seminal vesicle invasion. CONCLUSIONS: The CAPRA score showed high
      accuracy for predicting RFS. In particular, the three-group model was more useful
      for predicting RFS and pathologic outcomes. Therefore, the CAPRA score may be a
      useful prediction model for risk stratification and may help clinicians to
      develop localized prostate cancer treatment.

PMID- 24868337
TI  - Prognosis of prostate cancer with other primary malignancies.
AB  - PURPOSE: The objective was to investigate the clinicopathological characteristics
      and the prognosis of prostate cancer patients affected by other primary
      malignancies. MATERIALS AND METHODS: From 1990 to 2008, we retrospectively
      reviewed the medical records of 1,317 patients who underwent radical
      prostatectomy (RP) for prostate cancer. We assessed the effect of other primary
      malignancies on clinicopathological features, biochemical recurrence (BCR)-free
      survival, cancer-specific survival (CSS), and overall survival (OS). RESULTS: Of
      1,317 patients, at least one additional other primary malignancy was detected in
      187 patients (14.2%). A comparison of patient groups according to the presence or
      absence of other primary malignancies showed no significant differences in
      preoperative serum prostate-specific antigen concentrations, pathological Gleason
      scores, or pathological staging. Prostate cancer patients with other primary
      malignancies were older than patients without other primary malignancies
      (p<0.001). No significant differences in 5-year BCR-free survival (80.2% compared
      with 77.7%; p=0.656) or CSS (98.9% compared with 98.5%; p=0.733) were found
      between these groups, respectively. Five-year OS was significantly lower in
      prostate cancer patients with than in those without other primary malignancies
      (89.3% compared with 95.4%; p<0.001). Multivariate analysis showed that other
      primary malignancies diagnosed after RP for prostate cancer were independent
      predictors of OS (hazard ratio, 4.10; p<0.001) but not of BCR-free survival or
      CSS. Conversely, other primary malignancies diagnosed before RP for prostate
      cancer did not independently predict BCR-free survival, OS, or CSS. CONCLUSIONS:
      Prostate cancer prognosis after RP is not dependent on the presence or absence of
      other primary malignancies. However, other primary malignancies diagnosed after
      RP for prostate cancer negatively affect OS.

PMID- 24868338
TI  - Efficacy and Safety of the Selective alpha1A-Adrenoceptor Blocker Silodosin for
      Severe Lower Urinary Tract Symptoms Associated With Benign Prostatic Hyperplasia:
      A Prospective, Single-Open-Label, Multicenter Study in Korea.
AB  - PURPOSE: To evaluate the efficacy and safety of silodosin 8 mg once daily in a 12
      week treatment of subjects with severe lower urinary tract symptoms (LUTS)
      associated with benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: A
      total of 100 subjects from 10 urology centers in Korea were included in this
      study. The inclusion criteria were as follows: age >=50 years, International
      Prostate Symptom Score (IPSS) >=20, quality of life (QoL) score >=3, urine volume
      >=120 mL and maximal urinary flow rate (Qmax) <15 mL/s, and postvoid residual
      volume (PVR) <100 mL. We assessed the improvement of LUTS with change in IPSS,
      QoL score, Qmax, PVR, and adverse events at baseline and 4 and 12 weeks after
      treatment with silodosin 8 mg once daily. RESULTS: The IPSS values were 23.27+/
      3.34, 15.89+/-6.26, and 13.80+/-6.31 at baseline, 4, and 12 weeks, respectively,
      with significant improvements (p<0.0001, p=0.0214, respectively). QoL scores were
      4.44+/-0.85, 3.38+/-1.20, and 3.04+/-1.20 at baseline, 4, and 12 weeks,
      respectively, and the differences were statistically significant (p<0.0001).
      There was a significant difference in Qmax between baseline and 12 weeks
      (p<0.0001) but not in PVR (p=0.9404) during the clinical trial. The most frequent
      adverse event in this study was ejaculation failure with 13 cases. However, no
      subject dropped out because of ejaculation failure, and in 12 of the 13 cases it
      was fully resolved without further treatment. CONCLUSIONS: Silodosin 8 mg once
      daily may be effective and safe in Korean patients with severe LUTS associated
      with BPH.

PMID- 24868339
TI  - Chronic lower urinary tract symptoms in young men without symptoms of chronic
      prostatitis: urodynamic analyses in 308 men aged 50 years or younger.
AB  - PURPOSE: We investigated the etiologies of lower urinary tract symptoms (LUTS)
      and compared urodynamic characteristics between different diagnostic groups in
      young men with chronic LUTS. MATERIALS AND METHODS: We reviewed the medical
      records of 308 men aged 18 to 50 years who had undergone a urodynamic study for
      chronic LUTS (>=6 months) without symptoms suggestive of chronic prostatitis.
      RESULTS: The men's mean age was 40.4 (+/-10.1) years and their mean duration of
      symptoms was 38.8 (+/-49.2) months. Urodynamic evaluation demonstrated voiding
      phase dysfunction in 62.1% of cases (primary bladder neck dysfunction [PBND] in
      26.0%, dysfunctional voiding [DV] in 23.4%, and detrusor underactivity
      [DU]/acontractile detrusor [AD] in 12.7%) and a single storage phase dysfunction
      in 36.4% of cases (detrusor overactivity [DO] in 13.3%, small cystometric
      capacity in 17.9%, and reduced bladder sensation in 5.2%). Most of the
      demographic characteristics and clinical symptoms did not differ between these
      diagnostic groups. Whereas 53.9% of patients with voiding dysfunction had
      concomitant storage dysfunction, 69.6% of those with storage dysfunction had
      concomitant voiding dysfunction. Men with DV or DU/AD exhibited lower maximum
      cystometric capacity than did those with normal urodynamics. Low bladder
      compliance was most frequent among patients with PBND (10.0%, p=0.025). In
      storage dysfunctions, men with DO exhibited higher detrusor pressure during
      voiding than did those with other storage dysfunctions (p<0.01). CONCLUSIONS:
      Because clinical symptoms are not useful for predicting the specific urodynamic
      etiology of LUTS in this population, urodynamic investigation can help to make an
      accurate diagnosis and, potentially, to guide appropriate treatment.

PMID- 24868340
TI  - Unexpected Multidrug Resistance of Methicillin-Resistant Staphylococcus aureus in
      Urine Samples: A Single-Center Study.
AB  - PURPOSE: Infections of methicillin-resistant Staphylococcus aureus (MRSA) are
      becoming an increasingly concerning clinical problem. The aim of this study was
      to assess the development of MRSA in urine cultures in a major public university
      affiliated hospital and the therapeutical and hygiene-related possibilities for
      reducing resistance. MATERIALS AND METHODS: This study included 243 samples from
      patients diagnosed with MRSA infection over a period of 6 years. An agar
      diffusion test measured the effects of antimicrobial agents against bacteria
      grown in culture. The analyses were based on the guidelines of the Clinical and
      Laboratory Standards Institute. RESULTS: A regression analysis was performed,
      which showed 100% resistance to the following antibiotics throughout the entire
      testing period: carbapenem, cephalosporin (1st-4th generation), penicillin G,
      aminopenicillin, beta-lactamase, and isoxazolyl penicillin. However, a
      significant decrease in resistance was found for amikacin, gentamicin,
      clindamycin, levofloxacin, erythromycin, and mupirocin. CONCLUSIONS: MRSA showed
      a decreasing trend of antimicrobial resistance, except against carbapenem,
      cephalosporin (1st-4th generation), penicillin G, aminopenicillin, beta
      lactamase, and isoxazolyl penicillin, for which complete resistance was observed.

PMID- 24868341
TI  - Instillation of Hyaluronic Acid via Electromotive Drug Administration Can Improve
      the Efficacy of Treatment in Patients With Interstitial Cystitis/Painful Bladder
      Syndrome: A Randomized Prospective Study.
AB  - PURPOSE: In the treatment of interstitial cystitis, intravesical hyaluronic acid
      application may be suggested as a treatment option. In this randomized
      prospective study, the authors aimed to identify whether instilling the
      hyaluronic acid with electromotive drug administration (EMDA) would increase the
      tissue uptake and improve the efficacy. MATERIALS AND METHODS: The data of 31
      patients who had been diagnosed with bladder pain syndrome/interstitial cystitis
      (BPS/IC) between 2004 and 2005 were examined. The patients were randomized to two
      groups: patients in group A received hyaluronic acid directly with a catheter and
      patients in group B received hyaluronic acid with EMDA. The patients were
      followed for 24 months and the two groups were compared at certain time
      intervals. The primary end points of the study were visual analogue scale (VAS)
      score, global response assessment, and micturition frequency in 24 hours.
      RESULTS: There were 6 males and 25 females. The two groups were similar in
      baseline parameters. The decrease in VAS score and the micturition frequency in
      24 hours were significantly lower with EMDA at months 6 and 12. The difference
      between the two groups was not significant at months 1 and 24. Also, treatment
      with EMDA, positive KCl test, and pretreatment voiding frequency >17 were
      associated with higher response rates. CONCLUSIONS: Hyaluronic acid installation
      is an effective glycosaminoglycan substitution therapy in patients with BPS/IC.
      Instillation of hyaluronic acid via EMDA can improve the efficacy of the
      treatment; however, lack of long-term efficacy is the major problem with this
      glycosaminoglycan substitution therapy.

PMID- 24868342
TI  - Misplacement or migration? Extremely rare case of cardiac migration of a ureteral
      j stent.
AB  - A 29-year-old woman with mild back pain when coughing and suprapubic discomfort
      after voiding was admitted to Pusan National University Hospital. Two weeks
      earlier, she had undergone a hysterectomy and right-sided ureteroneocystostomy
      for uterine atony and right ureteral injury with bladder rupture. Computed
      tomography showed that a ureteral J stent extended from the right ovarian vein to
      the right cardiac chamber. The stent was retrieved via both femoral veins with a
      snare loop and pigtail catheter. Computed tomography showed that the urinary and
      vascular tracts were normal 5 months after the procedure. 

PMID- 24868343
TI  - Large bilateral adrenal leiomyomas presenting as calcified adrenal masses: a rare
      case report.
AB  - We report the case of a 55-year-old woman with bilateral, large, calcified
      adrenal tumors who was treated by laparoscopic adrenalectomy. The patient
      presented with upper abdominal discomfort for the past 5 years. Her imaging
      showed bilateral enlarged adrenal glands up to 10-cm size with punctate
      calcifications. Positron emission tomography scan demonstrated moderate
      fluorodeoxyglucose avidity in the left adrenal mass. Bilateral laparoscopic
      adrenalectomy was performed through a transperitoneal approach. The postoperative
      period was uneventful, and the patient was discharged on the third postoperative
      day. Histology findings were consistent with adrenal leiomyomatosis. 

PMID- 24868345
TI  - Dopamine agonist therapy in advanced Parkinson's disease.

PMID- 24868344
TI  - Apomorphine and levodopa infusion therapies for advanced Parkinson's disease.
AB  - Continuous infusion of levodopa or apomorphine provide constant dopaminergic
      stimulations are good alternatives to deep brain stimulation to control motor
      fluctuations in patients with advanced Parkinson's disease (PD). Apomorphine
      provides motor benefit similar to dopamine, but its long-term use is limited by
      compliance, mostly injection site skin reactions. Administration of
      levodopa/carbidopa by continuous duodenal infusion allows replacement of all oral
      medications and permits achievement of a satisfactory therapeutic response
      paralleled by a reduction in motor complication severity. However, this procedure
      is more invasive than apomorphine as it requires a percutaneous endoscopic
      gastrostomy Clinical experience with infusions shows that continuous dopaminergic
      stimulation of dopaminergic medications reduces dyskinesia and widens the
      therapeutic window in advanced PD. 

PMID- 24868346
TI  - Electrophysiologic assessments of involuntary movements: tremor and myoclonus.
AB  - Tremor is defined as a rhythmical, involuntary oscillatory movement of a body
      part. Although neurological examination reveals information regarding its
      frequency, regularity, amplitude, and activation conditions, the
      electrophysiological investigations help in confirming the tremor, in
      differentiating it from other hyperkinetic disorders like myoclonus, and may
      provide etiological clues. Accelerometer with surface electromyogram (EMG) can be
      used to document the dominant frequency of a tremor, which may be useful as
      certain frequencies are more characteristic of specific etiologies than others
      hyperkinetic disorders. It may show rhythmic bursts, duration and activation
      pattern (alternating or synchronous). Myoclonus is a quick, involuntary movement.
      Electrophysiological studies may helpful in the evaluation of myoclonus, not only
      for confirming the clinical diagnosis but also for understanding the underlying
      physiological mechanisms. Electroencephalogram (EEG)-EMG correlates can give us
      important information about myoclonus. Jerk-locked back-averaging and evoked
      potentials with recording of the long-latency, long-loop reflexes are currently
      available to study the pathophysiology of myoclonus. 

PMID- 24868347
TI  - The occurrence of fatigue in independent and clinically stable filipino patients
      with idiopathic Parkinson's disease.
AB  - BACKGROUND: Fatigue is a multidimensional problem affecting patients suffering
      from Parkinson's disease (PD). It is ranked as one of the most bothersome symptom
      of patients with Parkinson's disease. The study primarily aims to determine the
      presence of fatigue among clinically stable and independent Filipino patients
      suffering from idiopathic PD. METHODS: This study is a prospective cross
      sectional study. Recruited patients and control group were all Filipinos. Only
      independent patients with idiopathic, stable and non-fluctuating PD were included
      in the study. Those eligible underwent a multitude of screening tests to rule out
      presence of dementia (Mini Mental Status Examination, MMSE), depression
      (Montgomery-Asberg Depression Rating Scale, MADRS), anxiety (Hamilton Anxiety
      Scale, HAM-A) and sleep disturbance. Disease severity was assessed using the
      Unified Parkinson's Disease Rating Scale (UPDRS) and fatigue severity using both
      the Multicomponent Fatigue Index (MFI) and Fatigue Severity Inventory (FSI).
      RESULTS: Twenty-eight patients underwent the study. The mean Hoehn and Yahr
      staging was 1.79. Patients with PD scored higher on both FSI and MFI (individual
      dimension scores and total score) as compared to the normal controls.
      CONCLUSIONS: The outcome of the study confirmed the presence of fatigue (general,
      physical, mental), even in clinically stable and independent patients suffering
      from idiopathic PD, when compared with age-matched healthy controls.

PMID- 24868348
TI  - Comparison of Cerebral Glucose Metabolism between Possible and Probable Multiple
      System Atrophy.
AB  - BACKGROUND: To investigate the relationship between presenting clinical
      manifestations and imaging features of multisystem neuronal dysfunction in MSA
      patients, using (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG
      PET). METHODS: We studied 50 consecutive MSA patients with characteristic brain
      MRI findings of MSA, including 34 patients with early MSA-parkinsonian (MSA-P)
      and 16 with early MSA-cerebellar (MSA-C). The cerebral glucose metabolism of all
      MSA patients was evaluated in comparison with 25 age-matched controls. (18)F-FDG
      PET results were assessed by the Statistic Parametric Mapping (SPM) analysis and
      the regions of interest (ROI) method. RESULTS: The mean time from disease onset
      to (18)F-FDG PET was 25.9+/-13.0 months in 34 MSA-P patients and 20.1+/-11.1
      months in 16 MSA-C patients. Glucose metabolism of the putamen showed a greater
      decrease in possible MSA-P than in probable MSA-P (p=0.031). Although the Unified
      Multiple System Atrophy Rating Scale (UMSARS) score did not differ between
      possible MSA-P and probable MSA-P, the subscores of rigidity (p=0.04) and
      bradykinesia (p= 0.008) were significantly higher in possible MSA-P than in
      probable MSA-P. Possible MSA-C showed a greater decrease in glucose metabolism of
      the cerebellum than probable MSA-C (p=0.016). CONCLUSIONS: Our results may
      suggest that the early neuropathological pattern of possible MSA with a
      predilection for the striatonigral or olivopontocerebellar system differs from
      that of probable MSA, which has prominent involvement of the autonomic nervous
      system in addition to the striatonigral or olivopontocerebellar system.

PMID- 24868349
TI  - Unilateral standing leg tremor as the initial manifestation of Parkinson disease.
AB  - BACKGROUND: The aim of this study was to analyze the different forms of leg
      tremors exhibited while standing in patients with Parkinson disease (PD), and to
      determine if the type of leg tremor exhibited is indicative of prognosis or
      treatment response in PD patients. METHODS: We studied the clinical
      characteristics of five PD patients (all women; mean age, 59 years, range, 53-64
      years) with unilateral standing leg tremor as the initial manifestation of PD,
      including their electrophysiological findings and the results of long-term follow
      up. RESULTS: For each patient, parkinsonism either existed at the time of onset
      of the initial symptoms or developed later. Patient responses to drugs were
      generally good, but one patient showed a poor response to drugs, even though she
      had only a low frequency leg tremor. For two patients whom we could observe
      during the 10-year follow-up period, neither the leg tremor nor parkinsonism was
      aggravated. CONCLUSIONS: There are two forms of unilateral standing leg tremor in
      PD. One form is high frequency, similar to the primary orthostatic tremor. The
      other is low frequency and similar to the parkinsonian resting tremor. Based on
      these observations, it appears that progression might be slow if PD patients have
      standing leg tremor as the initial manifestation.

PMID- 24868350
TI  - Hyperhomocysteinemia in patients with Parkinson's disease and relationship to
      vitamin B level.
AB  - BACKGROUND: Plasma homocysteine (Hcy) levels are increased in patients with
      Parkinson's disease (PD) undergoing levodopa treatment. We measured the Hcy
      levels in PD patients and assessed the relationship between Hcy level and
      features of PD, cognitive function and vitamin B status. METHODS: Concentrations
      of Hcy, vitamin B12 and folate were measured in 33 PD patients and 41 normal
      control individuals. Mini-mental Status Examination (MMSE) was assessed in all
      subjects. In PD patients, Hoehn & Yahr stage and Unified Parkinson Disease Rating
      Scale (UPDRS) motor scores were also examined. RESULTS: Plasma Hcy levels were
      lower in PD patients than in control individuals. Hcy level was inversely
      correlated with vitamin B12 and folate levels in the PD group but not in control
      individuals. Age, symptom duration, UPDRS motor scores, MMSE score, levodopa dose
      and duration of treatment did not differ between patients with Hcy >14 MUmol/L
      and those with Hcy <14 MUmol/L. CONCLUSIONS: Plasma Hcy levels were increased in
      PD patients with levodopa treatment and were related to vitamin B level. These
      results indicate that vitamin supplementation may be beneficial in levodopa
      treated PD patients, although hyperhomocysteinemia did not affect the motor and
      cognitive status of PD patients.

PMID- 24868352
TI  - Painless legs and moving toes as an initial presentation of ischemic stroke.
AB  - Painless legs and moving toes is an unusual syndrome, which has not previously
      been reported as an initial presentation of ischemic stroke. We encountered a 78
      year-old woman who developed dysarthria and involuntary movement of her left toes
      that was clinically regarded as painless legs and moving toes. These symptoms
      appeared abruptly and simultaneously as the initial symptoms of stroke, and
      improved gradually with conservative management by intravenous hydration for a
      month. We suggest that, in our case, a cortical brain lesion caused by ischemic
      stroke might be associated with the development of painless legs and moving toes.

PMID- 24868351
TI  - Generalized chorea induced by an unilateral anterior cerebral artery territorial
      infarction.
AB  - Generalized chorea caused by unilateral cerebral infarction has rarely been
      reported. A 58-year-old woman presented involuntary movement in her all
      extremities after acute cerebral infarction on her right anterior cerebral artery
      territory. The involuntary movements were diagnosed as generalized chorea. We
      didn't find any cause of generalized chorea except the acute cerebral infarction.
      Here, we described the case of generalized chorea after unilateral cerebral
      infarction discussing the possible mechanisms. 

PMID- 24868353
TI  - Parkinsonsim due to a Chronic Subdural Hematoma.
AB  - Subdural hematoma is a rare cause of parkinsonism. We present the case of a 78
      year-old man with right-side dominant parkinsonism about 3 months after a minor
      head injury. MRI reveals a chronic subdural hematoma on the left side with mildly
      displaced midline structures. The parkinsonian features were almost completely
      disappeared after neurosurgical evacuation of the hematoma without any anti
      parkinson drug. 

PMID- 24868354
TI  - Novel compound heterozygous mutations in the pantothenate kinase 2 gene in a
      korean patient with atypical pantothenate kinase associated neurodegeneration.
AB  - Pantothenate kinase-associated neurodegeneration (PKAN) is an autosomal recessive
      disorder that is characterized by mutations in the pantothenate kinase 2 gene
      (PANK2) and typical magnetic resonance imaging findings. We report a case of
      atypical PKAN presenting with generalized dystonia. Our patient had compound
      heterozygous mutations in the PANK2 gene, including mutation in exon 3 (p.D268G)
      and exon 4 (p.R330P). To our knowledge, this patient is the first to have the
      p.R330P mutation and the second to have the p.D268G mutation. 

PMID- 24868355
TI  - Oculogyric crisis associated with disulfiram-induced pallidonigral lesion.
AB  - We report a man who developed oculogyric crisis one month after disulfiram
      intoxication. Brain MRI showed lesions involving bilateral globus pallidus and
      left substantia nigra. In our patient, neuronal discharges from pathologically
      reorganized basal ganglia circuit to the mid-brain ocular motor center might lead
      to tonic deviation of the eyes. 

PMID- 24868356
TI  - Adult onset familial cherry-red spot myoclonus.
AB  - We report a case of a 36-year-old woman with progressive generalized myoclonus
      that first became apparent 9 years ago. Her younger brother had similar problems.
      Examination of her eyes revealed cherry-red spots. Hexosaminidase A, beta
      galactosidase and neuraminidase activity were normal. Although the laboratory
      findings were negative, cherry-red spots, progressive myoclonus and autosomal
      recessive inheritance pattern suggested that she had an unknown type of lysosomal
      storage disease. 

PMID- 24868357
TI  - Positron emission tomography in the differential diagnosis of parkinsonism.
AB  - Positron emission tomography (PET) studies on presynaptic dopaminergic function
      can reveal hypofunction in early Parkinson's disease (PD) which may help in the
      early diagnosis especially in patients with mild symptoms. This hypofunction can
      be detected with fluorodopa (reflecting mainly aromatic amino acid decarboxylase
      activity of nigrostriatal terminals) or dopamine transporter ligands. These
      studies can also help to distinguish PD from essential tremor. However,
      investigations of presynaptic dopaminergic function are not useful in the
      differential diagnosis of parkinsonian syndromes. PET ligands, such as
      fluorodeoxyglucose (reflecting glucose metabolism) and dopamine receptor ligands,
      reflecting striatal neuronal function are better in this respect. Cardiac
      sympathetic function studies represent a new and interesting approach to improve
      differential diagnosis of parkinsonian syndromes but more studies are needed in
      larger patient populations with longer follow-up to evaluate the usefulness of
      these investigations. Multitracer approach combining ligands reflecting different
      aspects of dopaminergic neurotransmission and other physiological function will
      increase differential diagnostic accuracy. 

PMID- 24868358
TI  - Secondary dystonia-clinical clues and syndromic associations.
AB  - BACKGROUND: Dystonia is a hyperkinetic movement disorder defined by involuntary
      sustained muscle spasms and unusual postures. Etiologically, dystonic syndromes
      can be broadly divided into primary and secondary forms, dystonia-plus syndromes
      and heredodegenerative forms. In particular, diagnosis of secondary dystonic
      syndromes can be challenging in view of the variety of causes. PURPOSE: The
      purpose of this article is to highlight some clinical clues and syndromic
      associations as well as investigational findings which may be helpful in the
      approach to a patient with suspected secondary dystonia. METHODS: We outline
      characteristic clinical and neuroimaging findings which may be directive in the
      diagnostic process of dystonia patients and facilitate making the correct
      diagnosis, thus allowing initiating the best treatment. RESULTS: Secondary causes
      of dystonia include, among others, strategic brain lesions of various origins,
      metabolic disease, neurodegenerative conditions, and previous exposure to drugs
      or toxins. Presence of clinical signs including prominent oromandibular
      involvement, eye movement disorders, retinitis pigmentosa, deafness, peripheral
      neuropathy, parkinsonism or progressive dementia should alert the clinician to
      consider a secondary cause. Strategic lesions within the basal ganglia, but also
      within the brainstem, cerebellum or cortical areas may underlie dystonia and
      should thus be excluded. CONCLUSIONS: When thorough clinical examination reveals
      features atypical of primary dystonia, syndromic associations may help the
      clinician to narrow down the list of differential diagnosis. Directive
      investigations like neuroimaging may confirm the clinical suspicion.

PMID- 24868359
TI  - Usefulness of Diffusion-Weighted MRI for Differentiation between Parkinson's
      Disease and Parkinson Variant of Multiple System Atrophy.
AB  - BACKGROUND AND PURPOSE: Several studies have reported that diffusion-weighted
      imaging (DWI) is able to help discriminate a Parkinson variant of multiple system
      atrophy (MSA-p) from Parkinson's disease (PD) on the basis of the increased
      regional apparent diffusion coefficient (rADC). We analyzed the usefulness of DWI
      by using the rADC for differential diagnosis between MSA-p and PD and
      investigated the correlation between the rADC value and clinical features of MSA
      p and PD. METHODS: Twelve patients with PD and 10 with MSA-p were studied. The
      rADC value was determined in different brain regions, including the dorsal
      putamen (DP) and middle cerebellar peduncles (MCP). RESULTS: The rADC values of
      the DP showed a greater increase in MSA-p patients than in PD patients (p=0.03).
      MSA-p patients also presented increased rADC values of the MCP compared with PD
      patients (p=0.0001). In particular, the sensitivity, specificity and positive
      predictive values of the MCP rADC were higher than those of the DP rADC. However,
      DP and MCP rADC values were not correlated with clinical features in either MSA
      or PD patients. CONCLUSIONS: DWI discriminated between PD and MSA-p based on rADC
      values in DP and MCP. The MCP rADC value, in particular, could better
      discriminate MSA-p from PD.

PMID- 24868360
TI  - Anticholinergic agents can induce oromandibular dyskinesia.
AB  - BACKGROUND AND PURPOSE: Oromandibular dyskinesia (OMD) can occur spontaneously or
      they can be induced by the conventional dopamine receptor antagonists.
      Anticholinergic medications have rarely been reported to cause OMD in
      parkinsonian or non-parkinsonian patients. METHODS: We analyzed the clinical
      features of two parkinsonian and one non-parkinsonian patients who experienced
      OMD after anticholinergic medication. RESULTS: Each patient of our cases
      developed oromandibular symptoms in the temporal regions that were related to the
      addition of anticholinergic agents, and the symptoms were relieved following the
      discontinuation of the causative anticholinergic drugs. In one of our case,
      levodopa alone did not cause dyskinesia but augmented dyskinesia associated with
      anticholinergics. CONCLUSIONS: Here we report two parkinsonian and one non
      parkinsonian patients with OMD induced by the use of anticholinergic agents. In
      our cases, we could not find any other precipitating or actual secondary causes
      for the OMD symptoms in our patients. Furthermore, the fact that the OMD in our
      cases were ameliorated with cessation of anticholinergics suggests that it may be
      anticholinergic-induced.

PMID- 24868362
TI  - Paroxysmal chorea as a relapse of myelopathy in a patient with neuromyelitis
      optica.
AB  - Movement disorders secondary to intrinsic spinal cord disease are rare.
      Paroxysmal chorea has not yet been reported in the neuromyelitis optica (NMO). We
      report a 43-year-old woman with relapsing-remitting cervical myelopathy who
      developed paroxysmal chorea during clinical exacerbation of NMO. MRI scan of the
      cervical spine revealed a long segmental enhancing lesion, but brain MRI did not
      show any responsible abnormalities. Acute exacerbation of recurrent myelopathy in
      NMO may be associated with transient movement disorder. 

PMID- 24868361
TI  - Autonomic dysfunctions in parkinsonian disorders.
AB  - BACKGROUND AND PURPOSE: Symptoms of autonomic dysfunctions are common in the
      patients with parkinsonian disorders. Because clinical features of autonomic
      dysfunctions are diverse, the comprehensive evaluation is essential for the
      appropriate management. For the appreciation of autonomic dysfunctions and the
      identification of differences, patients with degenerative parkinsonisms are
      evaluated using structured questionnaire for autonomic dysfunction (ADQ).
      METHODS: Total 259 patients, including 192 patients with [idiopathic Parkinson's
      disease (IPD, age 64.6 +/- 9.6 years)], 37 with [multiple system atrophy (MSA,
      62.8 +/- 9.1)], 9 with [dementia with Lewy body (DLB, 73.9 +/- 4.3)], and 21 with
      [progressive supranuclear palsy (PSP, 69.4 +/- 9.6)]. The ADQ was structured for
      evaluation of the presence of symptoms and its severity due to autonomic
      dysfunction, covering gastrointestinal, urinary, sexual, cardiovascular and
      thermoregulatory domains. Patients were also evaluated for the orthostatic
      hypotension. RESULTS: Although dementia with Lewy body (DLB) patients were oldest
      and duration of disease was longest in IPD, total ADQ scores of MSA and PSP (23.9
      +/- 12.6 and 21.1 +/- 7.8) were significantly increased than that of IPD (15.1 +/
      10.6). Urinary and cardiovascular symptom scores of MSA and gastrointestinal
      symptom score of PSP were significantly worse than those of IPD. The ratio of
      patient with orthostatic hypotension in IPD was 31.2% and not differed between
      groups (35.1% in MSA, 33.3% in DLB and 33.3% in PSP). But the systolic blood
      pressure dropped drastically after standing in patients with MSA and DLB than in
      patients with IPD and PSP. CONCLUSIONS: Patients with degenerative parkinsonism
      showed widespread symptoms of autonomic dysfunctions. The severity of those
      symptoms in patients with PSP were comparing to that of MSA patients and worse
      than that of IPD.

PMID- 24868363
TI  - A case of vascular hemichorea responding to topiramate.
AB  - Although vascular chorea often comes into remission spontaneously, a few patients
      may remain with persistent movement disorder. Most movements respond well to
      neuroleptics as well as other antidopaminergic drugs, but some patients show poor
      responses to those neuroleptics. Topiramate is a widely used of broad-spectrum
      anticonvulsant possessing a complex mechanism of action. It has been proven to
      enhance gamma-aminobutyrate acid activity and to be effective in the control of
      other movement disorders. We describe a 63-year-old woman with intractable
      vascular hemichorea which was controlled with anti-convulsant, topiramate. 

PMID- 24868364
TI  - Hemidystonia as an initial manifestation of leptomeningeal metastasis.
AB  - A 76-year-old woman gradually developed action dystonia of the left hand and
      foot. Leptomeningeal metastasis of the right fronto-parietal area associated with
      gastric adenocarcinoma was found on the brain magnetic resonance imaging (MRI)
      and positron emission tomography (PET) studies. We discuss the mechanisms
      involved in the development of secondary hemidystonia and review dystonia
      associated with cortical lesions. 

PMID- 24868365
TI  - Disabling Head Tremor in a Patient with DYT1 Mutation.
AB  - Dystonic head tremor is known to be a feature in some patients with DYT1
      mutation. However, isolated tremor of the head without relevant cervical dystonia
      has rarely been described. We report here a patient with the three-bp GAG
      deletion in the DYT1 gene (904_906delGAG) who had severe head tremor in the frame
      of a generalized limb dystonia. 

PMID- 24868366
TI  - A cerebellar tremor in a patient with human immunodeficiency virus-1 associated
      with progressive multifocal leukoencephalopathy.
AB  - Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of
      the central nervous system (CNS) caused by JC virus infection in
      oligodendrocytes, especially in patients with acquired immunodeficiency syndrome
      (AIDS). Movement disorders associated with PML are very rare. Here, we report a
      case of PML in an AIDS patient who presented with a cerebellar tremor, caused by
      lesions in the cerebellar outflow tract. A cerebellar tremor can be a rare
      clinical manifestation in patients with PML. 

PMID- 24868368
TI  - A case of painful hemimasticatory spasm with masseter muscle hypertrophy
      responsive to botulinum toxin.
AB  - Hemimasticatory spasm (HMS) is a rare disorder of the trigeminal nerve
      characterized by paroxysmal involuntary contractions of the unilateral jaw
      closing muscles. HMS has been frequently described in association with facial
      hemiatrophy or localized scleroderma. A 42-year-old female presented with
      involuntary paroxysmal spasms of the left face, of 6 months duration. Her lower
      face on the left was markedly hypertrophied without skin lesions. An
      electrophysiological study indicated that the masseter reflexes and masseteric
      silent period were attenuated on the affected side. Surface electromyography
      demonstrated irregular bursts of motor unit potentials at high frequencies up to
      200 Hz. Magnetic resonance imaging of the head showed marked hypertrophy of the
      left masseter muscle. Biopsy of the hypertrophied masseter muscle was normal.
      Repeated local injections of botulinum toxin noticeably reduced the size of the
      hypertrophied muscle as well as improved the patient's symptoms. 

PMID- 24868367
TI  - A case of adrenoleukodystrophy presenting as progressive cerebellar dysfunction.
AB  - X-linked adrenoleukodystrophy (X-ALD) is a hereditary neurological disorder
      affecting the nervous system and adrenal cortex. The phenotype of X-ALD ranges
      from the rapidly progressive cerebral form to milder adrenomyeloneuropathy.
      However, cerebellar manifestations are rare. We report a case of
      adrenoleukodystrophy presenting as progressive cerebellar dysfunction resembling
      olivopontocerebellar degeneration, with a review of the literature. 

PMID- 24868369
TI  - Chorea in the both lower limbs associated with nonketotic hyperglycemia.
AB  - Hemichorea-hemiballism (HC-HB) is a complication of non-ketotic hyperglycemia
      (NKH); in NKH patients, the frequency of occurrence of HC-HB is greater than that
      of bilateral chorea. We report the case of a hyperglycemic patient who showed
      chorea in both the lower limbs. Magnetic resonance imaging (MRI) of the brain
      revealed high signal intensity on T1-weighted images of the bilateral
      dorsolateral putamen. The abnormal involuntary movements disappeared after oral
      administration of haloperidol. Our case report that chorea associated with NKH is
      correlated with the topography of the basal ganglia. 

PMID- 24868370
TI  - Human genetic variation and Parkinson's disease.
AB  - Parkinson's disease (PD) is a chronic neurodegenerative disorder with
      multifactorial etiology. In the past decade, the genetic causes of monogenic
      forms of familial PD have been defined. However, the etiology and pathogenesis of
      the majority of sporadic PD cases that occur in outbred populations have yet to
      be clarified. The recent development of resources such as the International
      HapMap Project and technological advances in high-throughput genotyping have
      provided new basis for genetic association studies of common complex diseases,
      including PD. A new generation of genome-wide association studies will soon offer
      a potentially powerful approach for mapping causal genes and will likely change
      treatment and alter our perception of the genetic determinants of PD. However,
      the execution and analysis of such studies will require great care. 

PMID- 24868371
TI  - Comparing Cerebral White Matter Lesion Burdens between Parkinson's Disease with
      and without Dementia.
AB  - Cerebral white matter lesions (CWMLs) have been suggested to be associated with
      an increased risk of dementia, disability, and death. CWMLs are more common in
      individuals with Alzheimer's disease (AD) than in normal elderly individuals of
      comparable age. Only a few studies have been done to determine whether CWMLs may
      influence cognitive decline in Parkinson's disease (PD). Fully developed PD with
      concurrent AD was reported to likely cause impaired cognition in spite of
      accumulating evidence suggesting that PD with dementia (PDD) is more closely
      associated with Lewy body (LB) pathology. Currently, contradictory data on the
      neuropathology of dementia in PD require further prospective clinicopathological
      studies in larger cohorts to elucidate the impact of AD and alpha-synuclein
      (SCNA) pathologies on the cognitive status in these disorders. Previous reports
      did not suggest CWMLs to be associated with an increased risk of PDD. After
      adjusting for age at death, age at onset of PD, and duration of PD, our recent
      study investigating CWMLs in PDD via autopsy has shown a positive correlation
      between the burden of CWMLs and PDD. The frequent co-existence of both LB and AD
      lesions suggests that both pathologies independently or synergistically
      contribute to both movement disorders and cognitive impairment. The individual
      and cumulative burden of CWMLs, LB lesions, and AD lesions may synergistically
      contribute to cognitive decline in LB disorders such as PDD. 

PMID- 24868373
TI  - Psychogenic gait disorders after mass school vaccination of influenza a.
AB  - BACKGROUND AND PURPOSE: Psychogenic movement disorders (PMD) after war or mass
      vaccination was reported and well known disease entity already. However, we have
      seldom been met those patients because we don't have any chance to experience of
      those events. Recently, influenza A (H1N1) spreads around world, and many
      countries have a program of mass vaccination of H1N1. Although PMD in adult is
      well characterized, childhood-onset PMD has not been extensively studied. CASE
      REPORTS: We present four children of psychogenic gait disorders (PGDs) after mass
      school vaccination of H1N1. They had fluctuating weakness and their prognosis was
      good. We confirmed all patients as PGD by placebo. CONCLUSIONS: Our four cases
      have two common characteristics. One is that all were young and their prognosis
      was good. And the other is that all were induced their abnormal gait symptoms
      after mass school vaccination. We observed that mass PMD has a different
      characteristics comparing to personal PMD, and PMD in children is differ from
      adult onset PMD.

PMID- 24868374
TI  - Action tremor associated with lamotrigine monotherapy.
AB  - Lamotrigine (LTG) is associated with a tremor when given in combination with
      valproic acid; however, a tremor associated with lamotrigine monotherapy is rare.
      Here, we report a case of positional and action tremor associated with
      lamotrigine use. Based on the temporal relationship, it is conceivable that
      lamotrigine increases serotonin transmission or affects basal ganglia dopamine
      activity, thereby causing the tremor. 

PMID- 24868372
TI  - Clinicopathological correlates of lewy body disease: fundamental issues.
AB  - Lewy body pathology (LBP) is the pathological hallmark of Lewy body diseases,
      such as Parkinson's disease and Lewy body dementia. Recent studies have shed new
      light on the role of LBP, the interactions of LBP with concomitant pathologies,
      and the propagation of LBP from the olfactory bulb and enteric nervous system to
      the central nervous system. The intrinsic difficulty with identifying
      clinicopathological correlates could be overcome by improving our understanding
      of the pathological evolution of LBP. 

PMID- 24868375
TI  - Hemichorea-hemiballism with a diabetic patient.
AB  - Chorea and ballism are movement disorders that result from a variety of
      conditions. They are an uncommon manifestation of diabetes mellitus. We report a
      52-year-old diabetic man who presented with acute onset chorea-ballism with a
      putaminal high-signal-intensity lesion on T1-weighted magnetic resonance imaging
      (MRI). 

PMID- 24868376
TI  - Restlessness with Manic Episodes due to Right Parietal Infarction.
AB  - Mood disorders following acute stroke are relatively common. However,
      restlessness with manic episodes has rarely been reported. Lesions responsible
      for post-stroke mania can be located in the thalamus, caudate nucleus, and
      temporal and frontal lobes. We present a patient who exhibited restlessness with
      manic episodes after an acute infarction in the right parietal lobe, and
      summarize the case reports involving post-stroke mania. The right parietal stroke
      causing mania in our case is a novel observation that may help us to understand
      the mechanisms underlying restlessness with mania following acute stroke. 

PMID- 24868377
TI  - Leucine-rich repeat kinase 2-linked Parkinson's disease: clinical and molecular
      findings.
AB  - Mutations in Leucine-rich repeat kinase 2 (LRRK2) gene are the most common cause
      of sporadic and familial late onset Parkinson's disease (PD). The G2019S common
      mutation has been identified about 1% of sporadic cases and 4-7% of familial
      cases. Over 50 variants have since been identified in LRRK2, and at least 7 of
      these are confirmed to be pathogenic. In addition to pathogenic mutations,
      several common polymorphisms in the LRRK2 gene (G2385R and R1628P) have been
      identified that may explain up to 10% of sporadic PD in Asian populations. LRRK2
      is a large complex multidomain protein with 2,527-amino-acid and the molecular
      weight is 286 kDa. LRRK2 multidomain protein consists of a catalytic core domain,
      kinase domain and a number of putative protein-protein interaction domains. LRRK2
      mutations found in PD families, including the G2019S and I2020T mutations show
      increased intrinsic kinase activity, when assessed with myelin basic protein as
      substrate. The modification of LRRK2 GTPase and kinase activity affecting
      residues in the ROC, COR and mitogen-activated protein kinase kinase kinases
      domains is believed to lead to neuronal cell death, but the pathways involved
      remain unclear. A number of in vivo models in C. elegans, D. melanogaster and
      mice have been developed to study the patho/physiological function of LRRK2.
      Based on current literature, a toxic gain of function in LRRK2 kinase activity is
      a possible pathophysiologic mechanism and thus inhibition of kinase activity in
      experimental models offers a potential therapeutic strategy for LRRK2-linked PD. 

PMID- 24868378
TI  - X-linked dystonia parkinsonism: clinical phenotype, genetics and therapeutics.
AB  - The clinical phenotype of X-Linked Dystonia Parkinsonism (XDP) is typically one
      that involves a Filipino adult male whose ancestry is mostly traced in the
      Philippine island of Panay. Dystonia usually starts focally in the lower limbs or
      oromandibular regions, then spreads to become generalized eventually.
      Parkinsonism sets in later into the disease and usually in combination with
      dystonia. /DYT3/ and /TAF1/ are the two genes associated with XDP. An SVA
      retrotransposon insertion in an intron of /TAF1/ may reduce neuron-specific
      expression of the /TAF1/ isoform in the caudate nucleus, and subsequently
      interfere with the transcription of many neuronal genes. Polypharmacy with oral
      benzodiazepines, anticholinergic agents and muscle relaxants leaves much to be
      desired in terms of efficacy. The medications to date that may appear beneficial,
      especially in disabling dystonias, are zolpidem, muscle afferent block with
      lidocaine-ethanol and botulinum toxin type A. Despite the few cases undergoing
      deep brain stimulation, this functional surgery has shown the greatest promise in
      XDP. An illustrative case of XDP in a family depicts the variable course of
      illness, including a bout of "status dystonicus," challenges in therapy,
      reckoning with the social impact of the disease, and eventual patient demise.
      Indeed, there remains some gaps in understanding some phenomenological, genetic
      and treatment aspects of XDP, the areas upon which future research directions may
      be worthwhile. 

PMID- 24868379
TI  - Four cases with peripheral trauma induced involuntary movements.
AB  - BACKGROUND AND PURPOSE: Although peripheral trauma induced movement disorders
      have been rarely reported, diagnostic criteria for peripherally induced movement
      disorders (PIMD) have been established. Because preexisting subclinical movement
      disorders, or secondary gain for compensation and legal purposes are difficult to
      confirm, differential diagnosis for physicians still remains difficult. CASE
      REPORTS: We present four patients developed movement disorders after relatively
      various intervals after traffic accident. Three patients of them showed tremor
      and one patient presented propriospinal myoclonus. In this report, we investigate
      whether peripheral trauma can lead to movement disorders and describe the
      relationship between peripheral injury and movement disorders in four cases.
      CONCLUSIONS: Injury was serious enough to develop involuntary abnormal movements
      with pain and the latency between injury and the onset of movements in all of
      cases was less than 1 year. Thus, our cases showed temporal and anatomical
      correlation between injury and the onset of movement disorder, strongly
      supporting the cause-and-effect relationship by previous diagnostic criteria for
      peripherally induced movement disorders.

PMID- 24868380
TI  - Cardiac (123)I-metaiodobenzylguanidine Scintigraphy in a Patient with Familial
      Parkinsonism with Parkin Gene Mutation.
AB  - A decreased cardiac (123)I-metaiodobenzylguanidine ((123)I-MIBG) uptake has been
      used as a powerful tool to identify Lewy body disease, such as idiopathic
      parkinson's disease (IPD). We performed cardiac (123)I-MIBG scintigraphy in
      patient with autosomal recessive juvenile parkinsonism (ARJP) with parkin gene
      mutation (PARK2). The findings showed normal cardiac (123)I-MIBG uptake.
      Therefore, although the clinical features of ARJP are sometimes quite similar to
      those of late-onset IPD, cardiac (123)I-MIBG scintigraphy may be used as a
      valuable tool to identify patients with IPD and to distinguish them from patients
      with other parkinsonian syndromes. 

PMID- 24868381
TI  - A case of juvenile huntington disease in a 6-year-old boy.
AB  - Huntington disease is a neurodegenerative disorder distinguished by the triad of
      dominant inheritance, choreoathetosis and dementia, usually with onset in the
      fourth and fifth decades. It is caused by an unstable cytosine-adenine-guanine
      (CAG) trinucleotide repeat expansion in the gene IT15 in locus 4p16.3. Juvenile
      HD that constitutes about 3% to 10% of all patients is clinically different from
      adult-onset form and characterized by a larger number of CAG repeats typically
      exceeding 60. We report a case of a 6-year-old boy with myoclonic seizure and 140
      CAG repeats confirmed by molecular genetic analysis. 

PMID- 24868382
TI  - A Case of Action-Induced Clonus that Mimicked Action Tremors and was Associated
      with Cervical Schwannoma.
AB  - Clonus is the rhythmic muscle contraction which usually occurs in patients with
      lesions involving descending motor pathways. Sometimes, rhythmic oscillation of
      action induced clonus could be confused to action tremor. We report a case of
      action induced clonus associated with cervical schwannoma which was misdiagnosed
      as essential tremor. The patient had spasticity in all limbs with exaggerated
      tendon reflexes, and passive stretch-induced clonus. Imaging and histological
      examinations revealed a schwannoma extending from C2 to C7. The lesion was
      partially removed by surgery. Even though essential tremor is a common disease,
      clinician have to do sufficient neurologic examination considering differential
      diagnosis. 

PMID- 24868383
TI  - Preserved glucose metabolism of deep cerebellar nuclei in a case of multiple
      system atrophy with predominant cerebellar ataxia: f-18 fluorodeoxyglucose
      positron emission tomography study.
AB  - The cerebellar glucose metabolism of multiple system atrophy with predominant
      cerebellar ataxia (MSA-C) is known to be decreased but is not defined among areas
      of cerebellum. We encountered a 54-year-old man who developed dizziness and
      progressive ataxia followed by urinary incontinence and orthostatic hypotension,
      all of those symptoms progressed relentlessly and the symptoms responded poorly
      to levodopa therapy. Visual analysis and statistical parametric mapping analysis
      of F-18 fluorodeoxyglucose positron emission tomography showed hypometabolism of
      both cerebellar hemisphere, severe at cortical area, and pons. There was clear
      sparing of deep cerebellar nuclei. Our report, as we know, shows the first case
      of preserved glucose metabolism of deep cerebellar nuclei relative to cerebellar
      cortex in an MSA-C patient. 

PMID- 24868384
TI  - Syndrome of inappropriate antidiuretic hormone secretion associated with
      pramipexole in a patient with Parkinson's disease.
AB  - The syndrome of inappropriate antidiuretic hormone secretion (SIADH) can be
      caused by a variety of drugs. Dopaminergic drugs might enhance the secretion of
      the antidiuretic hormone arginine vasopressin by reducing gamma-amino butyric
      acid release through the dopaminergic receptor in supraoptic nucleus. A 75-year
      old woman with Parkinson's disease developed asthenia, delirium, aggravated
      parkinsonian symptoms, and hypotonic hyponatremia along with the diagnostic
      criteria for SIADH during dose escalation of pramipexole. After pramipexole
      withdrawal, these symptoms disappeared, and sodium levels returned to normal
      values. The serum sodium levels of patients receiving pramipexole should be
      monitored, especially during dose escalation. 

PMID- 24868385
TI  - Rationale for therapeutic silencing of alpha-synuclein in Parkinson's disease.
AB  - The purpose of this paper is to provide the rationale for therapeutic silencing
      of the alpha-synuclein gene (SNCA) in Parkinson's disease (PD). The paper reviews
      the public health significance of PD; the causal links between rare SNCA variants
      and familial PD; the association of common SNCA variants and PD susceptibility;
      the association of SNCA variants also with age at onset and motor and cognitive
      outcomes in PD; therapeutic strategies targeting SNCA in PD; and preliminary
      findings and considerations on small interfering RNA-based therapies and PD. 

PMID- 24868386
TI  - Electrophysiological evidences of organization of cortical motor information in
      the Basal Ganglia.
AB  - During the last two decades, the many developments in the treatment of movement
      disorders such as Parkinson disease and dystonia have enhanced our understanding
      on organization of the basal ganglia, and this knowledge has led to other
      advances in the field. According to many electrophysiological and anatomical
      findings, it is considered that motor information from different cortical areas
      is processed through several cortico-basal ganglia loops principally in a
      parallel fashion and somatotopy from each cortical area is also well preserved in
      each loop. Moreover, recent studies suggest that not only the parallel processing
      but also some convergence of information occur through the basal ganglia.
      Information from cortical areas whose functions are close to each other tends to
      converge in the basal ganglia. The cortico-basal ganglia loops should be
      comprehended more as a network rather than as separated subdivisions. However,
      the functions of this convergence still remain unknown. It is important even for
      clinical doctors to be well informed about this kind of current knowledge because
      some symptoms of movement disorders may be explained by disorganization of the
      information network in the basal ganglia. 

PMID- 24868387
TI  - One View of the Current State of Understanding in Basal Ganglia Pathophysiology
      and What is Needed for the Future.
AB  - Deep Brain Stimulation (DBS), arguably, is the most dramatic development in
      movement disorders since the levodopa for Parkinson's disease. Yet, its
      mechanisms of action of DBS are unknown. However, DBS related research already
      has demonstrated that current concepts of basal ganglia pathophysiology are
      wrong. Specifically, the notion that over-activity of the globus pallidus interna
      causes parkinsonism, the basis for the most current theories, is no longer
      tenable. The development of any new theory will be aided by an understanding of
      how current theories are wrong and why have these flawed theories persist. Many
      of the problems of current theories are more matters of inference, assumptions,
      presumptions, and the accepted level of ambiguity than they are of fact.
      Consequently, it is imperative that these issues be addressed. Just as the
      inappropriate use of a tool or method is grounds for criticism, methods of
      reasoning are tools that can be used inappropriately and should be subject to
      discussion just as misuse of any other tool. Thorough criticism can provide very
      important lesions though the process could be mistaken as harsh or personal;
      neither is the case here. At the least, such analyzes can point to potential
      pitfalls that could be avoided in the development of new theories. As will be
      discussed, theories are important for the development of therapies but perhaps
      most important, for the acceptance of new therapies, as was the case for the
      recent resurgence of interest in surgical therapies. 

PMID- 24868388
TI  - Electrophysiologic evaluation of psychogenic movement disorders.
AB  - Psychogenic movement disorders (PMD) are a group of disorders which are in the
      border zone between neurology and psychiatry. All necessary laboratory
      investigations should be done to rule out an underlying organic disorder. While
      clinical acumen of a trained movement disorder specialist may be sufficient to
      diagnose most PMD, there are clinical situations where electrophysiological tests
      are required either to rule out an organic movement disorder or even diagnose a
      PMD. Current electrophysiological test are most useful for tremor, followed by
      jerks and least for spasms or dystonia. Commonly used electrophysiologic tests
      include multichannel surface electromyography (EMG), accelerometry,
      electroencephalography time locked with EMG, premovement potential
      (Bereitschaftspotential), and somatosensory evoked potentials. Psychogenic tremor
      is a low frequency tremor with variable frequency and duration of EMG bursts,
      entrainable, has a high coherence with voluntary movements, and presence of
      coactivation sign. Patients with psychogenic jerks have well organized triphasic
      pattern of activation of agonist and antagonist muscles. The jerks are associated
      with EMG bursts of long duration (usually > 70 ms), long and variable latencies
      in stimulus induced jerks, absence of craniocaudal pattern of muscle recruitment
      in apparent startle response, and often a Breitschaftspotential (premovement
      potential) precedes the jerk. Electrophysiological characterization of
      psychogenic dystonia is difficult and the tests are usually performed to rule out
      organic dystonia with characteristic findings. Finally, caution should be exerted
      in interpreting the electrophysiological tests as both false positive and false
      negative diagnosis of PMD may still occur. 

PMID- 24868389
TI  - Orthostatic hypotension in drug-naive patients with Parkinson's disease.
AB  - BACKGROUND AND PURPOSE: Orthostatic hypotension (OH) is known to be present even
      in patients with early Parkinson's disease (PD). To affirm the presence of OH and
      find correlation between OH and other dysautonomic symptoms in PD, this study has
      done in newly-diagnosed PD patients. METHODS: Forty-five non-demented patients
      with no prior history of treatment for PD were recruited (17 men, 63.8 +/- 10.1
      years of age). All the patients were evaluated for OH before starting
      medications. Autonomic symptoms were evaluated with structured questionnaires.
      Clinical characteristics of PD were evaluated (median Hoehn and Yahr stage 2.0 (1
      3), 1.3 +/- 1.1 years of disease duration), and comorbid medical conditions that
      could affect blood pressure were also recorded. RESULTS: OH was prevalent, and
      eighteen patients (40%) showed orthostatic hypotension, and twenty-seven (60%)
      did not (normotensive group). There was no significant difference in demographic
      and clinical characteristics between groups. The presence or severity of symptoms
      of autonomic dysfunction in the OH group also not differed from those of the
      normotensive group. CONCLUSIONS: OH was prevalent even in the early stage of PD,
      and was not related to presence or severity of any other symptoms of autonomic
      dysfunction. Our findings suggest that clinicians should pay attention to OH from
      the early stage of disease.

PMID- 24868390
TI  - The sequence effect in de novo Parkinson's disease.
AB  - BACKGROUND AND PURPOSE: The sequence effect (SE) in Parkinson's disease (PD)
      denotes progressive slowness in speed or progressive decrease in amplitude of
      repetitive movements. It is a well-known feature of bradykinesia and is
      considered unique in PD. Until now, it was well-documented in advanced PD, but
      not in drug-naive PD. The aim of this study is to know whether the SE can also be
      measured in drug-naive PD. METHODS: We measured the SE with a computer-based,
      modified Purdue pegboard in 4 drug-naive PD patients, which matched our previous
      study with advanced PD patients. RESULTS: We observed progressive slowness during
      movement, that is, SE. Statistical analysis showed a strong statistical trend
      toward the SE with the right hand, but no significance with the left hand. There
      was no statistical significance of SE with either the more or less affected
      hands. CONCLUSIONS: These results indicate that the SE can be identified in drug
      naive PD, as well as in advanced PD, with objective measurements and support the
      idea that the SE is a feature in PD observed during the early stage of the
      disease without medication.

PMID- 24868391
TI  - Cognitive impairments in multiple system atrophy of the cerebellar type.
AB  - BACKGROUND AND PURPOSE: We investigated the cognitive profiles in a large sample
      of patients with multiple system atrophy-cerebellar ataxia (MSA-C) and compared
      directly them in patients with clinical diagnosis of probable MSA-C without
      dementia and control subjects with intact cognition. METHODS: We prospectively
      enrolled 26 patients with clinical diagnosis of probable MSA-C. All patients
      underwent a standardized neuropsychological test of the Seoul Neuropsychological
      Screening Battery. RESULTS: The score of Korean version of the Mini- Mental State
      Examination was significantly lower in patients with MSA-C (27.2 +/- 2.5) than in
      control subjects (28.9 +/- 1.0, p = 0.003). Patients with MSA-C showed a
      significantly worse performance in visuospatial function, 3 words recall, verbal
      immediate, delayed and recognition memory, visual delayed memory, phonemic and
      sementic Controlled Oral Word Association Test, and ideomotor praxis (p < 0.05).
      CONCLUSIONS: Patients with MSA-C show more severe and more widespread cognitive
      dysfunctions than controls. Our results also indicate that cognitive dysfunction
      in patients with MCA-C is suggestive of disruption of the cerebellocortical
      circuits.

PMID- 24868392
TI  - Syndrome of inappropriate antidiuretic hormone secretion associated with
      pramipexole in a patient with Parkinson's disease.
AB  - The syndrome of inappropriate antidiuretic hormone secretion (SIADH) can be
      caused by a variety of drugs. Dopaminergic drugs might enhance the secretion of
      the antidiuretic hormone arginine vasopressin by reducing gamma-amino butyric
      acid release through the dopaminergic receptor in supraoptic nucleus. A 75-year
      old woman with Parkinson's disease developed asthenia, delirium, aggravated
      parkinsonian symptoms, and hypotonic hyponatremia along with the diagnostic
      criteria for SIADH during dose escalation of pramipexole. After pramipexole
      withdrawal, these symptoms disappeared, and sodium levels returned to normal
      values. The serum sodium levels of patients receiving pramipexole should be
      monitored, especially during dose escalation. 

PMID- 24868393
TI  - Unilateral negative myoclonus caused by herpes simplex virus encephalitis.
AB  - Various neurologic manifestations of herpes simplex virus (HSV) encephalitis have
      been reported on the literatures. Chorea, ballism, choreoathetosis and myoclonus
      were reported as movement disorders which might be related with brain lesion by
      HSV encephalitis, but negative myoclonus (NM) has never been reported before. NM
      can be characterized as a shock-like involuntary jerky movement caused by a
      sudden, brief interruption of muscle activity. We experienced a case of HSV
      encephalitis with NM in unilateral arm and leg. In polygraphic monitoring,
      electroencephalography (EMG) silent periods are 50-250 ms in duration with no
      detectable EMG correlate. 

PMID- 24868394
TI  - A case with improvement of blepharospasm by zolpidem.
AB  - Zolpidem is usually used for the treatment of insomnia as a hypnotic drug. It was
      also suggested to be effective in the treatment of dystonia in some studies. A 74
      year-old woman had been suffering from frequent and intense bilateral spasms of
      the eyelids for 20 years. She has been treated with botulinum toxin injection and
      taken some medications. But, she experienced a little effect and was not
      satisfied with those treatments. Her symptom was improved after taking Zolpidem
      which had been prescribed for insomnia by her primary physician. She did not show
      any improvement after placebo injection and neostigmine test. This is the first
      report which shows improvement of isolated blepharospasm by Zolpidem in Korea.
      Zolpidem can be one of useful alternative pharmacological treatments for
      blepharospasm. Further randomized, blinded, placebo-controlled studies are needed
      to validate this finding. 

PMID- 24868395
TI  - MicroRNAs in Experimental Models of Movement Disorders.
AB  - MicroRNAs (miRNAs) are small RNAs comprised of 20-25 nucleotides that regulates
      gene expression by inducing translational repression or degradation of target
      mRNA. The importance of miRNAs as a mediator of disease pathogenesis and
      therapeutic targets is rapidly emerging in neuroscience, as well as oncology,
      immunology, and cardiovascular diseases. In Parkinson's disease and related
      disorders, multiple studies have identified the implications of specific miRNAs
      and the polymorphisms of miRNA target genes during the disease pathogenesis. With
      a focus on Parkinson's disease, spinocerebellar ataxia, hereditary spastic
      paraplegia, and Huntington's disease, this review summarizes and interprets the
      observations, and proposes future research topics in this field. 

PMID- 24868396
TI  - Putaminal hypointensity in the parkinsonian variant of multiple system atrophy:
      simple visual assessment using susceptibility-weighted imaging.
AB  - BACKGROUND AND PURPOSE: Susceptibility-weighted imaging (SWI) has been shown to
      be superior in its ability to demonstrate brain mineralization than other
      conventional MR imaging. The goal of our study was therefore to assess the
      frequency and extent of putaminal hypointensity in parkinsonian variant MSA using
      SWI. METHODS: 11 patients with multiple system atrophy-parkinsonian type (MSA-p),
      30 patients with Parkinson's disease (PD), and age matched 30 controls were
      investigated using 3 Tesla MRI. The pattern of putaminal hypointensity was
      measured using a visual grading scale and scored from 0 to 3. RESULTS: Hemi- or
      bilateral putaminal hypointensity (a score of >= 2) and hyperintense rim were
      recognized in 81.8% and 54.5% of 11 MSA-p, respectively. The scores of putaminal
      hypointensity of MSA-p were significantly higher than other groups (p < 0.001), a
      score of >= 2 differentiated MSA-p from other groups. And all five patients with
      early disease stage also showed these characteristic findings. CONCLUSIONS: SWI
      appears to be useful for depicting putaminal hypointensity even in early stage of
      MSA-p. This finding suggests that iron deposition associated putaminal
      degeneration can occur early in the disease process.

PMID- 24868397
TI  - Lateralized effects of unilateral thalamotomy and thalamic stimulation in
      patients with essential tremor.
AB  - BACKGROUND AND PURPOSE: Stereotactic thalamotomy has been an effective surgical
      procedure in the treatment of medically refractory essential tremor (ET),
      however, little is known about the bilateral effects of unilateral ventralis
      intermedius (Vim) thalamotomy and Vim deep brain stimulation (DBS). We studied
      the lateralized effects of unilateral Vim thalamotomy and Vim DBS in ET patients.
      METHODS: Vim thalamotomy was performed in 6 patients and Vim DBS in 6. Patients
      were evaluated preoperatively and at 3 and 6 months postoperatively using the
      Clinical Rating Scale for Tremor (CRST). RESULTS: The contralateral Part A
      (tremor localization/severity rating) and Part B (specific motor tasks/function
      rating) subscores, and axial subscores of CRST significantly improved after
      unilateral Vim thalamotomy or Vim DBS. On the side ipsilateral to surgery, ET
      patients demonstrated no significant improvements in the Part A and Part B
      subscores of CRST. The Part C (functional disabilities resulting from tremor)
      subscores and total scores of CRST were significantly improved after surgery.
      CONCLUSIONS: Vim thalamotomy and DBS may be equally effective for the management
      of contralateral and axial tremor in ET patients, but both interventions may not
      improve tremor on the side ipsilateral to surgery.

PMID- 24868398
TI  - Analysis of the substantia innominata volume in patients with Parkinson's disease
      with dementia, dementia with lewy bodies, and Alzheimer's disease.
AB  - BACKGROUND AND PURPOSE: The substantia innominata (SI) contains the nucleus
      basalis of Meynert, which is the major source of cholinergic input to the
      cerebral cortex. We hypothesized that degeneration of the SI and its relationship
      to general cognitive performance differs in amyloidopathy and synucleinopathy.
      METHODS: We used magnetic resonance imaging (MRI)-based volumetric analysis to
      evaluate the SI volume in patients with amnestic mild cognitive impairment
      (aMCI), Alzheimer's disease (AD), Parkinson's disease-mild cognitive impairment
      (PD-MCI), PD with dementia (PDD), dementia with Lewy bodies (DLB), and healthy
      elderly controls. The correlation between SI volume and general cognitive
      performance, measured using the Korean version of the Mini-Mental State
      Examination (K-MMSE), was examined. RESULTS: Compared to control subjects, the
      mean normalized SI volume was significantly decreased in all of the other groups.
      The normalized SI volume did not differ between the subjects with PDD and DLB,
      whereas it was significantly smaller in subjects with PDD (p = 0.029) and DLB (p
      = 0.011) compared with AD. In subjects with PD-related cognitive impairment (PD
      MCI, PDD, or DLB), there was a significant positive correlation between the SI
      volume and K-MMSE score (r = 0.366, p < 0.001), whereas no correlation was seen
      in subjects with AD-related cognitive impairment (aMCI or AD). CONCLUSIONS: Our
      data suggest that the SI loss is greater in synucleinopathy-related dementia (PDD
      or DLB) than in AD and that the contribution of the SI to cognitive performance
      is greater in synucleinopathy than in amyloidopathy.

PMID- 24868399
TI  - Neuroleptic malignant syndrome in a patient with corticobasal degeneration.
AB  - Parkinson's disease is a principal underlying disease of neuroleptic malignant
      syndrome (NMS) occurring in parkinsonian disorders, but NMS may occur in patients
      with progressive supranuclear palsy and multiple system atrophy. We report first
      patient with corticobasal degeneration (CBD) who developed NMS after abrupt
      reduction of antiparkinsonian medication and concurrent infection. It should be
      kept in mind that the prevention of infectious illness, which is common
      complication in parkinson-plus syndrome, is important, and dose reduction or
      withdrawal of anti-parkinsonian medications should be carefully performed even in
      the patients with CBD who are expected to be unresponsive to levodopa treatment. 

PMID- 24868400
TI  - Oromandibular dyskinesia as the initial manifestation of late-onset huntington
      disease.
AB  - Huntington's disease (HD) is a neurodegenerative disorder characterized by a
      triad of choreoathetosis, dementia and dominant inheritance. The cause of HD is
      an expansion of CAG trinucleotide repeats in the HD gene. Typical age at onset of
      symptoms is in the 40s, but the disorder can manifest at any time. Late-onset (>=
      60 years) HD is clinically different from other adult or juvenile onset HD and
      characterized by mild motor problem as the initial symptoms, shorter disease
      duration, frequent lack of family history, and relatively low CAG repeats
      expansion. We report a case of an 80-year-old female with oromandibular
      dyskinesia as an initial manifestation of HD and 40 CAG repeats. 

PMID- 24868401
TI  - Concomitant appearance of pisa syndrome and striatal hand in Parkinson's disease.
AB  - Pisa syndrome is (PS) usually seen in patients receiving antipsychotic drugs and
      characterised by lateral flexion of trunk and axial dystonia. It is believed that
      antipsychotic drugs lead to dopamine blockage causing PS. We describe a
      Parkinson's disease patient who was doing well with levodopa/carbidopa for 3
      years and developed lateral flexion of trunk. His abnormal posture used to
      completely improve upon lying down position. He also had striatal hand deformity
      suggestive of focal dystonia. 

PMID- 24868402
TI  - Vocal polyps in tourette syndrome.
AB  - Hoarseness and dysphonia are often a result of vocal cord polyps which in turn,
      are linked to vocal trauma. We report the case of vocal polyps in the setting of
      a 27-year old male with a history only remarkable for Tourette syndrome. We
      review the literature regarding etiology and pathophysiology of vocal cord
      lesions and propose vocal tics in Tourette syndrome as an under-recognized
      etiology. In this way, we also review therapies that may aid in treating not only
      the vocal cord lesions but also particularly in the setting of vocal tics. 

PMID- 24868403
TI  - Dopa responsive slow orthostatic tremor in Parkinson's disease.
AB  - Slow orthostatic tremor (OT) occurred to longer and lower frequency regular
      rhythmic bursts in leg muscle upon standing. The slow OT was often able to
      clinically confused with orthostatic myoclonus. We described a Parkinson's
      disease patient with levodopa responsive slow OT. She showed abnormal movements
      of more regular rhythms and stable frequency on both legs on standing. These
      symptoms were aggravated at off state and improved by increasing levodopa. 

PMID- 24868405
TI  - Reorganization of the human somatosensory cortex in hand dystonia.
AB  - BACKGROUND AND PURPOSE: Abnormalities of finger representations in the
      somatosensory cortex have been identified in patients with focal hand dystonia.
      Measuring blood flow with positron emission tomography (PET) can be use to
      demonstrate functional localization of receptive fields. METHODS: A vibratory
      stimulus was applied to the right thumb and little finger of six healthy
      volunteers and six patients with focal hand dystonia to map their receptive
      fields using H2 (15)O PET. RESULTS: The cortical finger representations in the
      primary somatosensory cortex were closer to each other in patients than in normal
      subjects. No abnormalities were found in secondary somatosensory cortex, but the
      somatotopy there is less well distinguished. CONCLUSIONS: These data confirm
      prior electrophysiological and functional neuroimaging observations showing
      abnormalities of finger representations in somatosensory cortex of patients with
      focal hand dystonia.

PMID- 24868404
TI  - Preliminary study of intravenous amantadine treatment for ataxia management in
      patients with probable multiple system atrophy with predominant cerebellar
      ataxia.
AB  - BACKGROUND AND PURPOSE: Multiple system atrophy with predominant cerebellar
      ataxia is a disabling neurologic disease. However, effective management has not
      yet been established. We conducted a short-term, open-label preliminary study to
      assess the benefits of intravenous amantadine treatment in patients with probable
      multiple system atrophy with predominant cerebellar ataxia. METHODS: Twenty
      patients (10 male, 10 female) with probable multiple system atrophy with
      predominant cerebellar ataxia received 400 mg of amantadine by intravenous per
      day for 5 days. Ataxia severity was evaluated by the International Cooperative
      Ataxia Rating Scale before and after intravenous amantadine therapy and all
      subjects reported subjective improvement after intravenous amantadine treatment
      using a patient global impression scale. We analyzed the total and subscale
      scores by the ataxia scale and patient global impression scale. RESULTS: The mean
      age was 57.4 years (range: 47-72) and the mean disease duration was 30.8 months
      (range: 11-79). The ataxia severity significantly decreased after intravenous
      amantadine therapy from 42.5 to 37.3 (p < 0.001). The mean patient global
      impression scale for improvement was 2.9 and there were no side effects of
      intravenous amantadine treatment observed. When we assessed responders, the
      duration of intravenous amantadine effect was more than 1 month in 4 subjects of
      7 responders. CONCLUSIONS: Our findings suggest that intravenous amantadine
      treatment can be a safe management option in cerebellar ataxia, although the
      mechanism is unclear. Thus, further double-blind, long-term studies with a larger
      sample size are needed.

PMID- 24868406
TI  - Botulinum toxin clinic-based epidemiologic survey of adults with primary dystonia
      in East china.
AB  - BACKGROUND AND PURPOSE: Primary focal or segmental dystonia is a rare clinical
      condition. The clinical features of dystonia have not been evaluated in China. We
      performed a study to investigate the epidemiology of primary dystonia and its
      clinical variants in an adult population. METHODS: A Botulinum Toxin Clinic-based
      study was conducted in the period 18 May through 8 October 2010 in East China. We
      identified 523 dystonia patients from the Movement disorders and Botulinum Toxin
      clinic Cases. RESULTS: The most common focal dystonia were blepharospasm (59%),
      cervical dystonia (35%), limb dystonia (3%), oromandibular dystonia (2%) and
      laryngeal dystonia (1%). Males with primary dystonia were noted to have earlier
      age of onset. A female predominance was noted for most of the primary dystonias
      with a male to female ratio (M : F) ranging from 1 : 1.48 to 1 : 3. CONCLUSIONS:
      The epidemiological features of dystonia in East China we collected were similar
      to the report in Japan which contrasts partly with that reported in Europe.

PMID- 24868407
TI  - Hypomania induced by subthalamic nucleus stimulation in a Parkinson's disease
      patient: does it suggest a dysfunction of the limbic circuit?
AB  - The aim of this report was to describe a case of hypomania after deep brain
      stimulation of the subthalamic nucleus (STN DBS) in a Parkinson's disease (PD)
      patient. 59-year-old man with a 15-year history of PD underwent bilateral
      implantation of electrodes to the STN. Immediately after surgery, his motor
      function was markedly improved and his mood was elevated to hypomania. Fusion
      images of the preoperative MRI and postoperative CT scan showed that the
      electrodes were located in the medial portion of the STN. In this case,
      behavioral mood change was related to the deep brain stimulation. Moreover, the
      anatomical location and the functional alteration of the STN after the DBS
      surgery might be related to the regulatory system of the associative and limbic
      cortico-subcortical circuits. 

PMID- 24868408
TI  - Apparently ipsilateral parkinsonism in a patient with chronic subdural hematoma.
AB  - Symptomatic parkinsonism secondary to ipsilateral lesion is rarely reported.
      Although the contribution of the contralateral lesions was assumed in some cases,
      the pathomechanism remains undetermined. Herein we report a patient with a
      subdural hematoma, who developed parkinsonism in the ipsilateral hemibody.
      Structural and functional imaging suggests the contralateral dopaminergic
      dysfunction as the major culprit of apparently ipsilateral parkinsonism. 

PMID- 24868409
TI  - An elderly case of acute cerebellitis after alleged vaccination.
AB  - Acute cerebellitis (AC) is a benign and self-limiting inflammatory disease. It
      typically occurs as a primary infectious or postinfectious disorder. Although AC
      mostly presents in early childhood, it can appear in adult. A 66-year-old man
      admitted to our hospital because of limb and gait ataxia. Three weeks ago, he
      took an influenza vaccination. There was no abnormality on brain MRI with
      contrast enhancement, but Technetium-99m hexamethyl propylene amine oxime-single
      photon emission computed tomography (HMPAO-SPECT) showed markedly cerebellar
      asymmetry, suggesting hypoperfusion in the right cerebellum. Influenza
      vaccination can cause AC in the elderly and brain HMPAO-SPECT imaging is more
      useful than MRI in identifying patients with AC. 

PMID- 24868410
TI  - Psychogenic balance disorders: is it a new entity of psychogenic movement
      disorders?
AB  - The various reported psychogenic dyskinesias include tremor, dystonia, myoclonus,
      gait disorder, Parkinsonism, tics, and chorea. It is not easy to diagnose
      psychogenic movement disorders, especially in patients with underlying organic
      disease. We describe three patients with balance and/or posture abnormalities
      that occur when they stand up, start to move, or halt from walking, although
      their gaits are normal. One had an underlying unilateral frontal lobe lesion. All
      patients improved dramatically after receiving a placebo-injection or medication.
      These abnormal features differ from the previously reported features of astasia
      without abasia and of psychogenic gait disorders, including recumbent gait. We
      describe and discuss the patients' unique clinical characteristics. 

PMID- 24868411
TI  - Levodopa-induced facial dystonia in a case of progressive supranuclear palsy.
AB  - Progressive supranuclear palsy (PSP) is frequently misdiagnosed as other
      Parkinsonism because of clinical heterogeneity of PSP. We present here a case of
      a 67-year-old male patient with frontotemporal dementia-like cognitive impairment
      including language difficulties and abnormal behaviors. He showed severe facial
      dystonia after the levodopa treatment. Herein, we describe an unusual case of a
      patient presenting with PSP which, we believe could contribute to our knowledge
      about atypical leveodopa-induced facial dystonia in PSP. 

PMID- 24868413
TI  - Clinical features and disability milestones in multiple system atrophy and
      progressive supranuclear palsy.
AB  - Multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) are an
      adult-onset progressive neurodegenerative disorder that are known to display
      diverse clinical features and disease progression. We aim to characterize the
      clinical features and disease progression in patients with MSA and PSP by using a
      number of relevant disability milestones in Koreans. Forty-one patients with MSA
      and 14 patients with PSP had been enrolled. The mean age at onset of MSA-C, MSA-P
      and PSP was 56.7 +/- 7.8, 62.5 +/- 8.0, 68.9 +/- 6.1 years respectively. The most
      commonly reported symptom at disease onset is disequilibrium/dizziness in MSA-C,
      tremor in MSA-P and frequent falling in PSP. The mean duration of reaching
      milestones after disease onset in MSA-C were as followings: 20.8 (urinary
      incontinence), 22.9 (frequent falling), 27.8 (wheelchair bound), 31.8
      (dysarthria) and 35.8 months (diagnosis). The mean duration of reaching
      milestones after disease onset were 22.0 (urinary incontinence), 32.6 (frequent
      falling and diagnosis), 41.2 (dysarthria), 61.4 months (wheelchair bound) in MSA
      P and 16.8 (dysarthria), 21.6 (diagnosis), 21.7 (frequent falling), 24.0 months
      (wheel chair bound) in PSP. In the case of MSA, dizziness may occur for the first
      time. Thus, when the patient complains of non-specific dizziness, a follow-up
      examination to distinguish it from MSA can be helpful. There was a trend for
      patients with MSA-C to reach more disability milestones than in MSA-P and PSP
      before diagnosis. It may explain why patients with MSA-C are required more detail
      history taking and neurologic examination at an earlier stage. 

PMID- 24868414
TI  - A case of multiple system atrophy-cerebellar type preceded by dementia.
AB  - Multiple system atrophy (MSA) is a sporadic, adult-onset disease characterized by
      progressive degeneration of nervous systems including cerebellar, pyramidal,
      extrapyramidal, and autonomic system. Although a few recent studies reported that
      cognitive impairments could occur in patients with MSA, prominent dementia with
      progressive decline is not a typical clinical manifestation of MSA. In
      particular, dementia with MSA-cerebellar type is very rare. We have experienced a
      patient with 2-year history of severe cognitive impairment, who was finally
      diagnosed as MSA-cerebellar type. 

PMID- 24868415
TI  - Attention in Parkinson's disease mimicking suggestion in psychogenic movement
      disorder.
AB  - The various reported psychogenic movement disorders (PMDs) include tremor,
      dystonia, myoclonus, gait disorder, Parkinsonism, tics, and chorea. Although it
      is not easy to diagnose PMDs, several features such as distractibility,
      entrainment, suggestion and placebo trial are quite helpful to diagnose.
      Especially, distractibility or suggestion is a good tool to do in outpatient
      clinic easily. We describe a patient with parkinsonian features which were
      improved by internal suggestion to focusing attention. Initially, we suspected
      her diagnosis as PMDs; however she was confirmed with organic Parkinson's disease
      later. 

PMID- 24868412
TI  - Genetics of Parkinson's disease - a clinical perspective.
AB  - Discovering genes following Medelian inheritance, such as autosomal dominant
      synuclein and leucine-rich repeat kinase 2 gene, or autosomal recessive Parkin, P
      TEN-induced putative kinase 1 gene and Daisuke-Junko 1 gene, has provided great
      insights into the pathogenesis of Parkinson's disease (PD). Genes found to be
      associated with PD through investigating genetic polymorphisms or via the whole
      genome association studies suggest that such genes could also contribute to an
      increased risk of PD in the general population. Some environmental factors have
      been found to be associated with genetic factors in at-risk patients, further
      implicating the role of gene-environment interactions in sporadic PD. There may
      be confusion for clinicians facing rapid progresses of genetic understanding in
      PD. After a brief review of PD genetics, we will discuss the insight of new
      genetic discoveries to clinicians, the implications of ethnic differences in PD
      genetics and the role of genetic testing for general clinicians managing PD
      patients. 

PMID- 24868416
TI  - A case of intractable psychogenic essential palatal tremor.
AB  - Essential palatal tremor (EPT) is a rare disorder which shows rhythmic
      involuntary movement of the muscles of soft palate, especially tensor veli
      palatini muscle. EPT is classified by two subtypes, which is primary and
      secondary EPT. Secondary EPT includes psychogenic type. We describe a case of
      intractable psychogenic EPT. 

PMID- 24868418
TI  - Ventricular bigeminy after subcutaneous administration of apomorphine in a
      patient with refractory Parkinson's disease: a case report.
AB  - Apomorphine is a well established treatment for the management of sudden,
      unexpected and refractory levodopa-induced "off" states in fluctuating
      Parkinson's disease either as bolus injections or as continuous infusions.
      Incidents of atrial fibrillation associated with the administration of the drug
      have been reported in the past but no incidents of ventricular arrhythmias. We
      report a case of ventricular bigeminy recorded in a female patient after the
      administration of apomorphine. 

PMID- 24868419
TI  - A case of isolated middle cerebral artery stenosis with hemichorea and moyamoya
      pattern collateralization.
AB  - Isolated middle cerebral artery (MCA) stenosis in young patients with no other
      medical condition may be a unique pathologic entity with a benign long-term
      course. Generally, moyamoya disease shows a progression of stenosis from internal
      cerebral artery (ICA) to other intracranial vessel. A 26-year-old woman was
      admitted for choreic movements of the right arm and leg. Brain magnetic resonance
      imaging showed no stroke. Conventional angiography revealed 48% stenosis of the
      left M1 without ICA stenosis. Single photon emission computed tomography revealed
      perfusion asymmetry after acetazolamide injection, suggesting decreased uptake in
      the left basal ganglia and the cerebral cortex. Her hemichorea was mildly
      decreased with risperidone. One year later, follow-up angiography showed complete
      occlusion of the left M1 with neovascularization suggestive of moyamoya disease.
      The patient underwent bypass surgery and her hemichorea disappeared. This may be
      an atypical presentation of moyamoya disease. The bypass surgery was an effective
      measure for restoring the vascular insufficiency and, resultantly, controlling
      her hemichorea. 

PMID- 24868420
TI  - Acute hemichorea as an unusual presentation of internal carotid artery stenosis.
AB  - Involuntary movement associated with deep watershed ischemic lesions has been
      rarely reported. A 67-year-old woman presented with acute hemichorea on the left
      side. Magnetic resonance imaging showed acute infarcts in the anterior border
      zone. On perfusion studies, impaired cerebral blood flow was observed on the
      subcortical region sparing the basal ganglia. Cerebral angiogram confirmed severe
      stenosis in the right internal carotid artery. Her hemichorea gradually improved
      along with normalization of perfusion after carotid artery stenting with
      angioplasty. We suggest that impaired cerebral blood flow in critical watershed
      territories may be an important contributing factor in hemichorea associated with
      carotid occlusive disease. 

PMID- 24868421
TI  - Thrombocytopenia associated with levodopa treatment.
AB  - There were few cases of thrombocytopenia associated with levodopa. Herein, we
      report a patient with Parkinson's disease, who suffered thrombocytopenia related
      to long-term use of levodopa. 

PMID- 24868417
TI  - New perspective on parkinsonism in frontotemporal lobar degeneration.
AB  - Frontotemporal dementia (FTD) is the second most common type of presenile
      dementia. Three clinical prototypes have been defined; behavioral variant FTD,
      semantic dementia, and progressive nonfluent aphasia. Progressive supranuclear
      palsy, corticobasal degeneration, and motor neuron disease may possess clinical
      and pathological characteristics that overlap with FTD, and it is possible that
      they may all belong to the same clinicopathological spectrum. Frontotemporal
      lobar degeneration (FTLD) is a clinicopathological syndrome that encompasses a
      heterogenous group of neurodegenerative disorders. Owing to the advancement in
      the field of molecular genetics, diagnostic imaging, and pathology, FTLD has been
      the focus of great interest. Nevertheless, parkinsonism in FTLD has received
      relatively less attention. Parkinsonism is found in approximately 20-30% of
      patients in FTLD. Furthermore, parkinsonism can be seen in all FTLD subtypes, and
      some patients with familial and sporadic FTLD can present with prominent
      parkinsonism. Therefore, there is a need to understand parkinsonism in FTLD in
      order to obtain a better understanding of the disease. With regard to the
      clinical characteristics, the akinetic rigid type of parkinsonism has
      predominantly been described. Parkinsonism is frequently observed in familial
      FTD, more specifically, in FTD with parkinsonism linked to chromosome 17q (FTDP
      17). The genes associated with parkinsonism are microtubule associated protein
      tau (MAPT), progranulin (GRN or PGRN), and chromosome 9 open reading frame 72
      (C9ORF72) repeat expansion. The neural substrate of parkinsonism remains to be
      unveiled. Dopamine transporter (DAT) imaging revealed decreased uptake of DAT,
      and imaging findings indicated atrophic changes of the basal ganglia.
      Parkinsonism can be an important feature in FTLD and, therefore, increased
      attention is needed on the subject. 

PMID- 24868422
TI  - Orthostatic and supine blood pressures are associated with white matter
      hyperintensities in Parkinson disease.
AB  - BACKGROUND AND PURPOSE: Several reports on the elderly population have suggested
      that orthostatic hypotension is associated with white matter hyperintensities
      (WMH); however, little information is available on patients with Parkinson's
      disease (PD). METHODS: We analyzed the association blood pressure profiles during
      tilt table testing with WMH scores in 117 patients with PD. WMH were rated using
      the semiquantitative visual rating system proposed by Scheltens et al. RESULTS:
      The presence of orthostatic hypotension was associated with increasing tendency
      of WMH score and the blood pressure changes during tilting and supine blood
      pressure were positively correlated with increasing WMH score. CONCLUSIONS: This
      finding indicates that hemodynamic changes associated with orthostatic
      hypotension may be associated with white matter changes in patients with PD.

PMID- 24868423
TI  - Growth Hormone Deteriorates the Functional Outcome in an Experimental Model of
      Huntington's Disease Induced by 3-Nitropionic Acid.
AB  - BACKGROUND AND PURPOSE: Growth hormone (GH) has been frequently used to control
      the aging process in healthy individuals, probably due to its slowing effect on
      senescence-associated degeneration. Mitochondrial dysfunction is related to the
      aging process, and one of the chemical models of Huntington's disease is that it
      can be induced by mitochondrial toxin. To investigate the potential application
      of GH to modify the progression of Huntington's disease (HD), we examined whether
      GH can protect the functional deterioration by striatal damage induced by 3
      nitropropionic acid (3NP). METHODS: 3NP (63 mg/kg/day) was delivered to Lewis
      rats by osmotic pumps for five consecutive days, and the rats received
      intraperitoneal administration of GH or vehicle (saline) throughout the
      experiment. Neurological deficits and body weight were monitored. A 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test was performed to
      further determine the mitochondrial activity in cultured N18TG2 neuroblastoma
      cells in vitro. RESULTS: 3NP-treated rats showed progressive neurologic deficits
      with striatal damage. Application of GH accelerated behavioral deterioration,
      particularly between day 3 and day 5, resulting in reduced survival outcome. The
      body weights of rats given 3NP were decreased, but GH did not affect such
      decrease compared to the non-treated control group. The effect of GH on cultured
      neuronal cells was a decrease in the MTT absorbance, suggesting a lower number of
      cells in a dose dependent pattern. CONCLUSIONS: Those results suggest that
      application of GH to a 3NP-induced experimental model of HD deteriorates the
      progress of functional deficits, possibly disturbing mitochondrial activities.

PMID- 24868424
TI  - Amantadine induced corneal edema in a patient with primary progressive freezing
      of gait.
AB  - Amantadine is commonly used for Parkinsonism. However amantadine can induce
      adverse corneal reaction. Here we report a patient with primary progressive
      freezing of gait who had severe corneal edema associated with amantadine, which
      was reversible after discontinuation of the amantadine. This report alerts
      neurologists for this reversible but potentially critical corneal edema in
      patients with Parkinsonism who are receiving amantadine. 

PMID- 24868425
TI  - Hot cross bun sign following bilateral pontine infarction: a case report.
AB  - The hot cross bun sign is characterized by cruciform T2 signal hyperintensity in
      the pons and has been reported to be a specific but not pathognomic for multiple
      system atrophy. It reflects degeneration of pontine neurons and transverse
      pontocerebellar fibers, regardless of the underlying pathogenic process. Here, we
      report a case of hot cross bun sign following bilateral pontine infarction due to
      Wallerian degeneration of the pontocerebellar fibers. 

PMID- 24868426
TI  - Common sports-related infections: a review on clinical pictures, management and
      time to return to sports.
AB  - There is a relationship between exercise and changes in immunity. So athletes are
      prone to different medical problems such as injuries and infections. Infection is
      an important medical problem which could be a reason for athletes' absence from
      training. The relationship between physical activity and immune system,
      characteristics of different types of infections in athletes with emphasis on
      special clinical presentations or complications, time to return to physical
      activity and training and strategies to prevent development and transmission of
      infections in athletes or physically active people are the main topics of this
      review. 

PMID- 24868427
TI  - A Comparison of Anthropometric and Training Characteristics between Female and
      Male Half-Marathoners and the Relationship to Race Time.
AB  - PURPOSE: Lower limb skin-fold thicknesses have been differentially associated
      with sex in elite runners. Front thigh and medial calf skin-fold appear to be
      related to 1,500m and 10,000m time in men but 400m time in women. The aim of the
      present study was to compare anthropometric and training characteristics in
      recreational female and male half-marathoners. METHODS: The association between
      both anthropometry and training characteristics and race time was investigated in
      83 female and 147 male recreational half marathoners using bi- and multi-variate
      analyses. RESULTS: In men, body fat percentage (beta=0.6), running speed during
      training (beta=-3.7), and body mass index (beta=1.9) were related to half
      marathon race time after multi-variate analysis. After exclusion of body mass
      index, r (2) decreased from 0.51 to 0.49, but body fat percentage (beta=0.8) and
      running speed during training (beta=-4.1) remained predictive. In women, body fat
      percentage (beta=0.75) and speed during training (beta=-6.5) were related to race
      time (r (2) =0.73). For women, the exclusion of body mass index had no
      consequence on the predictive variables for half-marathon race time. CONCLUSION:
      To summarize, in both female and male recreational half-marathoners, both body
      fat percentage and running speed during training sessions were related to half
      marathon race times when corrected with co-variates after multi-variate
      regression analyses.

PMID- 24868428
TI  - Physiological Responses and Performance Analysis Difference between Official and
      Simulated Karate Combat Conditions.
AB  - PURPOSE: This study aimed to compare physiological responses and time-motion
      analysis between official and simulated karate combat. METHODS: Ten high-level
      karatekas participated in this study, which included official and simulated
      karate combat. RESULTS: Karatekas used more upper-limb attack techniques during
      official combat compared to simulated ones (6+/-3 vs 3+/-1; P=0.05,
      respectively). For official and simulated karate matches, the numbers of high
      intensity actions (i.e. offensive and defensive fighting activity) were 14+/-6
      and 18+/-5, respectively (P>0.05), lasting from <1s to 5s each. Total fighting
      activity phase was lower during official compared to simulated matches (21.0+/
      8.2s vs 30.4+/-9.9s, P<0.01, respectively). Effort (10.0+/-2.8s) to rest (11.9+/
      2.7s) ratio (E:R) was 1:1 and high-intensity actions (1.6+/-0.3s) to rest (11.9+/
      2.7s) ratio was higher than 1:7 during simulated combat. During official karate
      match, the activity and rest duration were 10.0+/-3.4s and 16.2+/-4.1s,
      respectively (E:R ratio 1:1.5), while high-intensity actions were 1.5+/-0.3s,
      resulting in an E:R ratio of 1:11. Blood lactate concentration was higher during
      official (11.14+/-1.82 mmol.l(-1)) compared to simulated karate combat (7.80+/
      2.66 mmol.l(-1)) (P<0.05). Subjective perceived exertion differed significantly
      between official and simulated combat (14+/-2 vs. 12+/-2; P<0.05, respectively).
      The majority of karatekas' perceived exertion was higher in the lower limb muscle
      groups irrespective of the karate combat condition. CONCLUSION: Official and
      simulated matches differ considerably, therefore coaches should create new
      strategies during training sessions to achieve the same effort and pause profile
      of competitive matches and/or that athletes should be submitted to frequent
      competitions to adapt themselves to the profile of this event.

PMID- 24868429
TI  - Neuromuscular and metabolic responses to three different resistance exercise
      methods.
AB  - PURPOSE: The aim of this study was to compare the effect of resistance exercise
      with three different methods on integrated electromyography (IEMG) and metabolic
      responses in recreational athletes. METHODS: Twenty four males (mean 23.59+/-0.87
      years) were randomly assigned to three experimental groups. Participants
      performed knee extension exercises: Slow (SL: 3-3, 3s for each concentric and
      eccentric action with 50% of 1 RM), Normal (NH: 1-1, 1 s for each concentric and
      eccentric action 80% of 1 RM) and Traditional (TH: 2-4, 2s for concentric and 4s
      for eccentric action with 80% of 1 RM). Plasma lactate, glucose and triglyceride
      concentration and IEMG was measured before and immediately after performing four
      sets of resistance exercise. RESULTS: Each method significantly decreased IEMG
      (P<0.05), but there was no significant difference between groups. Lactate was
      increased following TH and NH more than SL method (P<0.05). Each method
      significantly increased plasma glucose (P<0.05). Work considering time under
      tension (workTUT) was higher (P<0.05) during TH method than the other methods and
      during SL it was higher than NH method (P<0.05). Volume load was higher (P<0.05)
      during NH than the other two methods and during TH it was higher than SL method
      (P<0.05). CONCLUSION: These results indicate that exercise intensity during the
      resistance exercise is important for the enhancement of lactate responses, but
      the slow resistance exercise method could induce acute neuromuscular response as
      much as high intensity methods. It seems that this method will be advantageous
      for those who want to increase acute neuromuscular changes with low exercise
      intensity and volume.

PMID- 24868430
TI  - Association of ambient air quality with pulmonary function of youngster
      footballers.
AB  - PURPOSE: Air pollution has remained a major health concern in Kolkata. The
      present study was carried out to analyze the association between the levels of
      air pollutants and pulmonary function of youngster footballers living in two
      different air pollutant zones of Kolkata, West Bengal. METHODS: Air pollution
      data of the two ambient air quality-monitoring stations located at
      Rabindrabharati and Victoria Memorial was collected for the period from January
      2012 to March 2012. Study was conducted on two hundred and twenty boys of the age
      range 14-16 years living within 3km radius of the two monitoring stations. Sample
      consisted of 60 footballers (30 from Rabindrabharati and 30 from Victoria
      Memorial) and 160 sedentary boys (80 from Rabindrabharati and 80 from Victoria
      Memorial). They were investigated for their spirometric lung functions by the
      method and technique recommended by American Thoracic Society. Results were
      expressed as mean +/- SD and independent samples T test was conducted to compare
      between two groups. RESULTS: Results revealed that particulate matter (PM10),
      oxides of sulfur (SO2) concentrations were significantly higher in
      Rabindrabharati zone, whereas no significant differences were noted in oxides of
      nitrogen (NO2) and carbon monoxide (CO) concentrations though values were higher
      at Rabindrabharati than Victoria Memorial. Forced vital capacity (FVC), forced
      expiratory volume in 1 second (FEV1), forced mid expiratory flow (FEF25-75%),
      maximum voluntary ventilation (MVV) were significantly lower both in footballers
      (P<0.05) and sedentary boys (P<0.01) of Rabindrabharati zone. CONCLUSION:
      Exposure to high air pollutant concentration might be associated with reduced
      pulmonary function in both sedentary and trained boys in spite of the fact that
      regular participation in training program may improve pulmonary function.

PMID- 24868431
TI  - Physical Activity during a Prolonged Congested Period in a Top-Class European
      Football Team.
AB  - PURPOSE: The aim of the present study was to examine the variation in physical
      activity of elite soccer players within successive prolonged periods of fixture
      congestion over 5 months of competition during the competitive season 2011-2012.
      METHODS: Sixteen international players, classified into 6 positions (central
      defenders: CD; full-backs: FB; central defensive midfielders: CDM; wide
      midfielders: WM; central attacking midfielders: CAM; forwards: FW), were examined
      during the French First League, French Cup, and UEFA Champion's League matches.
      The total distance covered at light (<12 km.h(-1)), sustained-cruising (>18-21
      km.h(-1)), high (>21-23 km.h(-1)), very high (>23-25 km.h(-1)), sub-maximal (>25
      27 km.h(-1)), and maximal (>27 km.h(-1)) intensity running (IR) were measured and
      analysed using a semi-automatic match analysis system (Amisco ProTM). RESULTS: No
      differences were observed between congested and non-congested periods (two vs.
      one match a week, respectively) for the total distance covered at all the speed
      thresholds over 18 km.h(-1), with no variation in physical fitness over the 5
      studied months. Specifically to the playing positions, regardless of the
      congestion periods, FB and WM covered more distance than CDM over 21km.h(-1); FB,
      WM and FW covered similar distances for all running intensities; and CD and CDM
      covered shorter distance during non-congested compared to congested periods
      (P<0.05) at light-IR. CONCLUSION: The present study reveals that prolonged
      congested match fixture did not affect the high-intensity physical activity of
      top-class soccer players during official games during a 5 months fixture period.

PMID- 24868434
TI  - Exercise therapy for total tear of rotator cuff: a case report.
AB  - BACKGROUND: Shoulder pain is one of the most common problems in ages older than
      60 years of age. Rotator cuff pathology is the most common etiology of shoulder
      pain. Most of rotator cuff pathologies are treated conservatively in old ages and
      exercise therapy is not an accepted intervention for management of rotator cuff
      tear yet. CASE PRESENTATION: The case was a man of 53 years age with shoulder
      pain who had total tear of supraspinatus tendon and biceps tendinitis in the
      right shoulder. He had regularly gone swimming, mountain climbing and running in
      the last 10 years. The case was managed by exercise therapy for 3 months and
      physical modalities for 20 sessions. Shoulder pain and his function and right
      shoulder range of motion increased after 3 months. Para clinical findings did not
      change after treatment, though. The improvements continued 15 months after the
      beginning of the treatment. CONCLUSION: Exercise therapy was very effective for
      improving pain and function in total tear of supraspinatus tendon and tendinitis
      of biceps.

PMID- 24868433
TI  - Repeated Acceleration Ability (RAA): A New Concept with Reference to Top-Level
      Field and Assistant Soccer Referees.
AB  - PURPOSE: To perform an exploratory characterization of repeated sprint sequences
      (RSS) and repeated acceleration sequences (RAS) in top level soccer referees.
      METHODS: 7 field and 7 assistant referees were monitored during 2007 America's
      Soccer Cup with GPS technology. Sprints of >18 km.h(-1) and accelerations of >1.5
      m.s(-2) were considered as high intensity activities. RSS and RAS were defined as
      a minimum of 3 consecutive bouts interspersed with a maximum of 45 s. RESULTS:
      Field and assistant referees performed substantially more accelerations than
      sprints. Neither field nor assistant referees recorded any RSS. In contrast,
      total distance performing RAS amounted to ~37% and ~20% of the total distance
      covered by accelerations during the entire match for field and assistant
      referees, respectively. Only field referees exhibited fatigue-related reductions
      in RAS characteristics between halves. CONCLUSION: The results of the present
      study would appear to support the appropriateness of a repeated acceleration
      ability (RAA) concept, instead of the repeated sprint ability (RSA) concept, in
      soccer referees. Further studies should assess RAS in referees and athletes of
      different team sports for designing better training exercises and physiological
      testing.

PMID- 24868432
TI  - Surface Electromyography Assessments of the Vastus medialis and Rectus femoris
      Muscles and Creatine Kinase after Eccentric Contraction Following Glutamine
      Supplementation.
AB  - PURPOSE: L-glutamine is the most abundant amino acid found in human muscle and
      plays an important role in protein synthesis and can reduce the levels of
      inflammation biomarkers and creatine kinase (CK) after training sessions. Delayed
      onset muscle soreness (DOMS) develops after intense exercise and is associated
      with an inflammatory response. The purpose of this study was to investigate the
      effect of glutamine supplementation on surface electromyography activity of the
      vastus medialis muscle (VMM) and rectus femoris muscle (RFM) and levels of
      creatine kinase after an eccentric contraction. METHODS: SEVENTEEN HEALTHY MEN
      (AGE: 22.35+/-2.27yr; body mass: 69.91+/- 9.78kg; height: 177.08+/-4.32cm) were
      randomly assigned to experimental (n=9) and control groups (n=8) in a double
      blind manner. In both groups, subjects were given L-glutamine supplementation
      (0.1g.kg(-1)) or placebo three times a week for 4 weeks. Median frequency (MDF)
      and mean power frequency (MPF) for VMM and RFM muscles and also CK measurements
      were performed before, 24h and 48 h after a resistance training session. The
      resistance training included 6 sets of eccentric leg extensions to exhaustion
      with 75% of 1RM. RESULTS: There was no significant difference between groups for
      MDF or MPF in VMM and RFM. The difference of CK level between the groups was also
      not significant. CONCLUSION: The results of this study indicate that glutamine
      supplementation has no positive effect on muscle injury markers after a
      resistance training session.

PMID- 24868435
TI  - Benign paroxysmal positional vertigo caused by swimming.

PMID- 24868436
TI  - European perspectives in thoracic surgery.
AB  - Europe, the old Continent, has been the cradle of thoracic surgery from the
      beginning of the last century. The structure and the activities of the European
      Society of Thoracic Surgeons (ESTS) activities are directed to enlighten the
      path, provide the tools and set the standards for a quality inspired practice in
      thoracic surgery. 

PMID- 24868437
TI  - VATS anatomic lung resections-the European experience.
AB  - Video-assisted thoracoscopic surgery (VATS) has undergone significant evolution
      over several decades. Although endoscopic instruments continued to improve, it
      was not until 1992 that the first VATS lobectomy for lung cancer was performed.
      Despite significant seeding of such procedure in several thoracic units globally,
      the uptake was slow and frustrating. Many surgeons considered it complex and
      unsafe being skeptic about its oncological validity. The last decade has
      witnessed significant change of practice in many thoracic units with a new
      generation of VATS thoracic surgeons. Additionally the technique has been
      refined, standardized and proved its validity and superiority in lung cancer
      treatment. 

PMID- 24868438
TI  - Robotic thoracic surgery: from the perspectives of European chest surgeons.
AB  - Although thoracic surgery is one of the fastest growing programs, the results of
      robotic thoracic surgery reports are presented very rarely. In this manuscript,
      the development of robotic thoracic surgery programs in Europe and the initial
      results are discussed. Several European countries lead the development of robotic
      surgery in the world, especially for lung cancer surgery and for thymus-thymoma
      surgery. Yet, we may not recognize any major advantage in the outcome when
      compared to video-assisted thoracic surgery (VATS). But, certainly, the superior
      capabilities of the intraoperative instrumentation of robotic surgery will be
      beneficial. More experience in robotic surgery may provide superior results in
      oncological, physiological and life quality measurements. 

PMID- 24868440
TI  - Adjuvant or neoadjuvant chemotherapy for NSCLC.
AB  - In functionally fit patients with localized disease surgical resection remains
      the treatment of choice. There is also good evidence to support the use of
      chemotherapy in stages II-III. However, whether to use neoadjuvant or adjuvant
      therapy has been the topic of much debate. With its strong evidence base,
      adjuvant chemotherapy has been adopted in the European Society of Medical
      Oncology clinical practice guidelines for early and locally advanced stages II
      III non-small-cell lung cancer (NSCLC), with consideration of adjuvant therapy in
      those with stage IB but with tumours >4 cm in size. There are fewer trials
      comparing neoadjuvant therapy plus surgery with surgery alone. Even less has been
      carried out directly comparing neoadjuvant with adjuvant therapy. The NATCH trial
      demonstrated no difference in survival between adjuvant and neoadjuvant arms,
      whilst others have yet to be completed. Meta-analysis also demonstrates no
      appreciable difference between the two methods. With such a strong body of
      evidence, however, postoperative delivery of chemotherapy remains the timing of
      choice in NSCLC. 

PMID- 24868439
TI  - Surgical management of advanced non-small cell lung cancer.
AB  - More than 75% of the cases of non-small cell lung cancer (NSCLC) are diagnosed in
      advanced stages (IIIA-IV). Although in these patients the role of surgery is
      unclear, complete tumor resection can be achieved in selected cases, with good
      long-term survival. In this review, current indications for surgery in advanced
      NSCLC are discussed. In stage IIIA (N2), surgery after induction chemotherapy
      seems to be the best option. The indication of induction chemotherapy plus
      radiotherapy is debatable due to potential postoperative complications but
      recently reported experiences have not shown a higher postoperative risk in
      patients after chemo and radiotherapy induction even if pneumonectomy is
      performed. In cases of unexpected N2 found during thoracotomy, lobectomy plus
      systematic nodal dissection is recommended mostly for patients with single
      station disease. In stage IIIB, surgery is only the choice for resectable T4N0-1
      cases and should not be indicated in cases of N2 disease. Favorable outcomes are
      reported after extended resections to the spine and mediastinal structures.
      Thorough and individualized discussion of each stage IIIB case is encouraged in
      the context of a multidisciplinary team. For stage IV oligometastatic cases,
      surgery can still be included when planning multimodality treatment. Brain and
      adrenal gland are the two most common sites of oligometastases considered for
      local ablative therapy. 

PMID- 24868441
TI  - Management of thymic tumors: a European perspective.
AB  - Thymic tumors are rare mediastinal tumors, which are considered as orphan
      diseases due to their low prevalence. The most recent histologic classification
      divides thymic tumors into thymomas, thymic carcinomas (TC) and neuroendocrine
      thymic tumors (NETT). Until recently, clinical research on thymic tumors has been
      primarily represented by single-institution experiences usually scattered over a
      long time period in order to accumulate a sufficient number of patients for
      clinical analysis. Europe has played a pivotal role in the advancement of the
      clinical research on thymus in the past years. In the last decade, there has been
      an increased interest in thymic malignancies in the scientific community. The
      European Society of Thoracic Surgeons (ESTS), the most representative society of
      general thoracic surgeons in the world, established a dedicated thymic working
      group in 2010 with the intent to provide a platform among ESTS members with a
      specific interest in thymic malignancies. The present review is intended to
      provide, through the description of the activity of the ESTS thymic working group
      and its published results, an overview of the European contribution to the thymic
      research. A brief overview of the state-of-the-art of clinical presentation,
      diagnosis, staging and histologic classification of thymic tumors is also
      provided, along with the most recent therapeutic advancements. 

PMID- 24868442
TI  - Management of malignant pleural mesothelioma-The European experience.
AB  - Management of malignant pleural mesothelioma (MPM) remains a clinical challenge
      and the incidence of the disease will continue to increase worldwide. Several
      aspects of mesothelioma treatment are discussed controversially, in particular,
      regarding extent and best type of surgery, radiotherapy, and the role of
      neoadjuvant or adjuvant treatment. However, best survival data is reported from
      groups using multimodality treatment including macroscopic complete resection
      (MCR) achieved by either extrapleural pneumonectomy (EPP) or (extended)
      pleurectomy/decortication for patients qualifying from the tumor biology, stage,
      and patient's performance status and comorbidities. Several aspects have to be
      considered during surgery but morbidity and mortality have been reduced at
      experienced centres. The final analysis of extended selection algorithms is
      pending. 

PMID- 24868443
TI  - Current management of esophageal cancer.
AB  - Management of esophageal cancer has evolved since the two last decades.
      Esophagectomy remains the primary treatment for early stage esophageal cancer
      although its specific role in superficial cancers is still under debate since the
      development of endoscopic mucosal treatment. To date, there is strong evidence to
      consider that locally advanced cancers should be recommended for a multimodal
      treatment with a neoadjuvant chemotherapy or a combined chemoradiotherapy (CRT)
      followed by surgery. For locally advanced squamous cell carcinoma or for a part
      of adenocarcinoma, some centers have proposed treating with definitive CRT to
      avoid related-mortality of surgery. In case of persistent or recurrent disease, a
      salvage esophagectomy remains a possible option but this procedure is associated
      with higher levels of perioperative morbidity and mortality. Despite the debate
      over what constitutes the best surgical approach (transthoracic versus
      transhiatal), the current question is if a minimally procedure could reduce the
      periopertive morbidity and mortality without jeopardizing the oncological results
      of surgery. Since the last decade, minimally invasive esophagectomy (MIE) or
      hybrid operations are being done in up to 30% of procedures internationally.
      There are some consistent data that MIE could decrease the incidence of the
      respiratory complications and decrease the length of hospital-stay. Nowadays,
      oncologic outcomes appear equivalent between open and minimally invasive
      procedures but numerous phase III trials are ongoing. 

PMID- 24868445
TI  - The European general thoracic surgery database project.
AB  - The European Society of Thoracic Surgeons (ESTS) Database is a free registry
      created by ESTS in 2001. The current online version was launched in 2007. It runs
      currently on a Dendrite platform with extensive data security and frequent
      backups. The main features are a specialty-specific, procedure-specific,
      prospectively maintained, periodically audited and web-based electronic database,
      designed for quality control and performance monitoring, which allows for the
      collection of all general thoracic procedures. Data collection is the "backbone"
      of the ESTS database. It includes many risk factors, processes of care and
      outcomes, which are specially designed for quality control and performance audit.
      The user can download and export their own data and use them for internal
      analyses and quality control audits. The ESTS database represents the gold
      standard of clinical data collection for European General Thoracic Surgery. Over
      the past years, the ESTS database has achieved many accomplishments. In
      particular, the database hit two major milestones: it now includes more than 235
      participating centers and 70,000 surgical procedures. The ESTS database is a
      snapshot of surgical practice that aims at improving patient care. In other
      words, data capture should become integral to routine patient care, with the
      final objective of improving quality of care within Europe. 

PMID- 24868444
TI  - The biomolecular era for thoracic surgeons: the example of the ESTS Biology Club.
AB  - Understanding basic mechanisms of lung disease may help to move forward the
      management of our patients. Molecular biology has affected our diagnostic and
      therapeutic pathways in the direction of personalized medicine not only for
      thoracic malignancies. Accordingly, thoracic surgeons are becoming increasingly
      aware that specific knowledge of genetic and epigenetic alterations may influence
      their clinical behavior-from the ward to the operating room (OR). In this
      continuously evolving scenario, surgical societies have perceived the increasing
      relevance of biomolecular medicine in the practice of modern thoracic surgery.
      More recently, in the spirit of mutual collaboration between sister societies,
      the European Society of Thoracic Surgeons (ESTS) has adopted the concept of the
      American Association for Thoracic Surgery (AATS) incorporating one session
      dedicated to the Biology Club within the Annual Meeting Program. The aim of the
      ESTS Biology Club is to outline and sponsor the new profile of the surgeon
      scientist during the only world meeting exclusively focused on general thoracic
      surgery. The following article will summarize the significance of this and give
      an update on molecular biology tools for thoracic malignancies. 

PMID- 24868446
TI  - The European educational platform on thoracic surgery.
AB  - As the largest scientific organisation world-wide exclusively dedicated to
      general thoracic surgery (GTS), the European Society of Thoracic Surgeons (ESTS)
      recognized that one of its priorities is education. The educational platform
      designed ESTS addresses not only trainees, but also confirmed thoracic surgeons.
      The two main aims are (I) to prepare trainees to graduation and to the
      certification by the European Board of Thoracic Surgery and (II) to offer
      opportunities for continuous medical education in the perspective of life-long
      learning and continuous professional development to certified thoracic surgeons.
      It is likely that recertification will become an obligation during the coming
      decade. At its inception, the platform differentiated two different events. A 6
      day course emphasizing on theoretic knowledge was created in Antalya in 2007. The
      same year, a 2-day school oriented to practical issues with hands-on in the
      animal lab was launched in Antalya. These two teaching tracks need further
      development. In the knowledge track, we intend to organize highly specialized 2
      day courses to deepen insight into theoretical questions. The skill track will be
      implemented by specialized courses for high technology such as tracheal surgery,
      ECMO, robotics or chest wall reconstruction. In order to promote tomorrows'
      leadership, we created an academic competence track giving an insight into
      medical communication, methodology and management. We also had to respond to an
      increasing demand from the Russian speaking countries, where colleagues may face
      problems to attend western meetings, and where the language bareer may be a major
      impediment. We initiated a Russian school with three events yearly in 2012.
      Contemporary teaching must be completed with an e-learning platform, which is
      currently under development. The school activities are organized by the
      educational committee, which is headed by the ESTS Director of Education,
      assisted by coordinators of the teaching tracks and e-learning platform. Ongoing
      discussions concern development of contemporary teaching techniques and measure
      of outcome. The major challenge for the coming years is harmonisation of training
      and certification in thoracic surgery in the European space. 

PMID- 24868447
TI  - European institutional accreditation of general thoracic surgery.
AB  - To improve standardization of general thoracic surgery (GTS) practice across
      Europe, the European Society of Thoracic Surgeons (ESTS) has implemented a
      program of Institutional Accreditation. We reviewed the methods and rules of
      engagement of this program. A composite performance score (CPS) including outcome
      and process indicators is used to measure institutional performance and assess
      eligibility for accreditation. Eligible units are invited to participate and
      accept a local audit performed by an external auditors team composed by data
      inspectors and thoracic surgeons. In addition to data quality, a series of
      structural, procedural and qualification characteristics are inspected. Once the
      visit is complete, the team will produce an audit report to be sent to the
      members of the database committee for deliberation on the institutional
      accreditation of that unit. The Database committee will send an executive report
      to the ESTS Executive Committee for their final decision on the accreditation. 

PMID- 24868448
TI  - An Association between BK Virus Replication in Bone Marrow and Cytopenia in
      Kidney-Transplant Recipients.
AB  - The human polyomavirus BK (BKV) is associated with severe complications, such as
      ureteric stenosis and polyomavirus-associated nephropathy (PVAN), which often
      occur in kidney-transplant patients. However, it is unknown if BKV can replicate
      within bone marrow. The aim of this study was to search for BKV replication
      within the bone marrow of kidney-transplant patients presenting with a
      hematological disorder. Seventy-two kidney-transplant patients underwent bone
      marrow aspiration for cytopenia. At least one virus was detected in the bone
      marrow of 25/72 patients (35%), that is, parvovirus B19 alone (n = 8), parvovirus
      plus Epstein-Barr virus (EBV) (n = 3), cytomegalovirus (n = 4), EBV (n = 2), BKV
      alone (n = 7), and BKV plus EBV (n = 1). Three of the eight patients who had BKV
      replication within the bone marrow had no detectable BKV replication in the
      blood. Neutropenia was observed in all patients with BKV replication in the bone
      marrow, and blockade of granulocyte maturation was observed. Hematological
      disorders disappeared in all patients after doses of immunosuppressants were
      reduced. In conclusion, an association between BKV replication in bone marrow and
      hematological disorders, especially neutropenia, was observed. Further studies
      are needed to confirm these findings. 

PMID- 24868449
TI  - Attitudes to medication after kidney transplantation and their association with
      medication adherence and graft survival: a 2-year follow-up study.
AB  - Background. Nonadherence to medication is a common problem after kidney
      transplantation. The aim of this study was to explore attitudes towards
      medication, adherence, and the relationship with clinical outcomes. Method.
      Kidney recipients participated in a Q-methodological study 6 weeks after
      transplantation. As a measure of medication adherence, respondents completed the
      Basel Assessment of Adherence to Immunosuppressive Medications Scale (BAASIS((c))
      interview). Moreover, the intrapatient variability in the pharmacokinetics of
      tacrolimus was calculated, which measures stability of drug intake. Data on graft
      survival was retrieved from patient records up to 2 years after transplantation.
      Results. 113 renal transplant recipients (19-75 years old) participated in the
      study. Results revealed three attitudes towards medication adherence-attitude 1:
      "confident and accurate," attitude 2: "concerned and vigilant," and attitude 3:
      "appearance oriented and assertive." We found association of attitudes with
      intrapatient variability in pharmacokinetics of tacrolimus, but not with self
      reported nonadherence or graft survival. However, self-reported nonadherence
      immediately after transplantation was associated with lower two-year graft
      survival. Conclusion. These preliminary findings suggest that nonadherence
      shortly after kidney transplantation may be a risk factor for lower graft
      survival in the years to follow. The attitudes to medication were not a risk
      factor. 

PMID- 24868450
TI  - Provider Education about Glaucoma and Glaucoma Medications during Videotaped
      Medical Visits.
AB  - Objective. The purpose of this study was to examine how patient, physician, and
      situational factors are associated with the extent to which providers educate
      patients about glaucoma and glaucoma medications, and which patient and provider
      characteristics are associated with whether providers educate patients about
      glaucoma and glaucoma medications. Methods. Patients with glaucoma who were newly
      prescribed or on glaucoma medications were recruited and a cross-sectional study
      was conducted at six ophthalmology clinics. Patients' visits were videotape
      recorded and patients were interviewed after visits. Generalized estimating
      equations were used to analyze the data. Results. Two hundred and seventy-nine
      patients participated. Providers were significantly more likely to educate
      patients about glaucoma and glaucoma medications if they were newly prescribed
      glaucoma medications. Providers were significantly less likely to educate African
      American patients about glaucoma. Providers were significantly less likely to
      educate patients of lower health literacy about glaucoma medications. Conclusion.
      Eye care providers did not always educate patients about glaucoma or glaucoma
      medications. Practice Implications. Providers should consider educating more
      patients about what glaucoma is and how it is treated so that glaucoma patients
      can better understand their disease. Even if a patient has already been educated
      once, it is important to reinforce what has been taught before. 

PMID- 24868451
TI  - Emerging therapies for noninfectious uveitis: what may be coming to the clinics.
AB  - Corticosteroids along with other immunomodulatory therapies remain as the
      mainstay of treatment tor all patients with noninfectious uveitis (NIU). However,
      the systemic side effects associated with the long-term use of these drugs has
      encouraged the development of new therapeutic agents in recent times. This review
      article discusses upcoming therapeutic agents and drug delivery systems that are
      currently being used to treat patients with NIU. These agents mediate their
      actions by blocking specific pathways involved in the inflammatory process.
      Agents discussed in this review include full or recombinant monoclonal antibodies
      against interleukins such as IL-17 (secukinumab), IL-l (gevokizumab), and IL-6
      (tocilizumab and sarilumab), antibody fragments against inflammatory cytokines
      such as TNF- alpha (ESBA 105) and T-cell inhibitors such as fusion proteins
      (abatacept), and next generation calcineurin inhibitors (voclosporin). In
      addition, administration of immune modulatory therapies using methods such as
      iontophoresis (EGP-437) and intravitreal injection (sirolimus) for the treatment
      of NIU' uveitis has also been discussed. 

PMID- 24868452
TI  - Clinical efficacy of intravitreal ranibizumab in early and mid-idiopathic
      choroidal neovascularization.
AB  - Background. To compare visual outcomes and spectral-domain optical coherence
      tomography results following intravitreal ranibizumab treatment for early and mid
      idiopathic choroidal neovascularization (ICNV). Methods. This retrospective, case
      controlled study examined 44 patients with ICNV in one eye initially treated with
      intravitreal ranibizumab (0.5 mg). Further intravitreal treatments were
      administered as necessary. Patients were divided into two groups according to
      disease duration, that is, <=3 months or 3-6 months (early and mid-groups), and
      the data were compared. Results. All patients completed at least 12 months of
      follow-up. Significant differences were observed between the groups in best
      corrected visual acuity and in central macular thickness (CMT) reduction at all
      five follow-up visits. At the last follow-up (12 months), 19 early group eyes
      (79.1%) and 10 mid group eyes (50.0%) had statistically significant visual gains
      of >15 early treatment diabetic retinopathy study (ETDRS) letters (chi (2) =
      4.130, P = 0.042). The mean number of injections was significantly higher  (P =
      0.0001) in the mid group (2.53 +/- 1.76) than in the early group (1.22 +/- 1.01).
      Conclusions. Early intravitreal ranibizumab for ICNV can result in better visual
      prognoses, more obvious decreases in CMT, and fewer injections. 

PMID- 24868453
TI  - Suppression of Face Perception during Saccadic Eye Movements.
AB  - Lack of awareness of a stimulus briefly presented during saccadic eye movement is
      known as saccadic omission. Studying the reduced visibility of visual stimuli
      around the time of saccade-known as saccadic suppression-is a key step to
      investigate saccadic omission. To date, almost all studies have been focused on
      the reduced visibility of simple stimuli such as flashes and bars. The extension
      of the results from simple stimuli to more complex objects has been neglected. In
      two experimental tasks, we measured the subjective and objective awareness of a
      briefly presented face stimuli during saccadic eye movement. In the first task,
      we measured the subjective awareness of the visual stimuli and showed that in
      most of the trials there is no conscious awareness of the faces. In the second
      task, we measured objective sensitivity in a two-alternative forced choice (2AFC)
      face detection task, which demonstrated chance-level performance. Here, we
      provide the first evidence of complete suppression of complex visual stimuli
      during the saccadic eye movement. 

PMID- 24868454
TI  - Management of uveitis-related choroidal neovascularization: from the pathogenesis
      to the therapy.
AB  - Inflammatory choroidal neovascularization is a severe but uncommon complication
      of uveitis, more frequent in posterior uveitis such as punctate inner
      choroidopathy, multifocal choroiditis, serpiginous choroiditis, and Vogt-Koyanagi
      Harada syndrome. Its pathogenesis is supposed to be similar to the wet age
      related macular degeneration: hypoxia, release of vascular endothelial growth
      factor, stromal cell derived factor 1-alpha, and other mediators seem to be
      involved in the uveitis-related choroidal neovascularization. A review on the
      factors implicated so far in the pathogenesis of inflammatory choroidal
      neovascularization was performed. Also we reported the success rate of single
      studies concerning the therapies of choroidal neovascularization secondary to
      uveitis during the last decade: photodynamic therapy, intravitreal bevacizumab,
      and intravitreal ranibizumab, besides steroidal and immunosuppressive therapy.
      Hereby a standardization of the therapeutic approach is proposed. 

PMID- 24868455
TI  - Vision related quality of life in patients with keratoconus.
AB  - Purpose. The purpose of this study is to evaluate the vision related quality of
      life in patients with keratoconus by using the National Eye Institute Visual
      Function Questionnaire-25 (NEI-VFQ-25). Methods. Thirty patients presented with
      keratoconus (keratoconus group) and 30 healthy patients (control group) were
      included in this study. Twenty patients were using rigid gas permeable and 10
      patients were not using contact lenses in keratoconus group. High and low
      contrast visual acuity and mean K values of the patients were recorded. Each
      subject completed the 25-item NEI-VFQ-25. Results. All subscales of NEI-VFQ-25
      were lower in the keratoconus patients. The difference was more evident in the
      subscales of general vision, ocular pain, near vision, vision-specific mental
      health, vision-specific role difficulties, and peripheral vision (P < 0.05).
      Overall composite score was 75.2 +/- 17.2 in the keratoconus group and 93.2 +/-
      5.6 in the control group (P = 0.00). Contact lens wearers had higher best
      corrected visual acuity in comparison with noncontact lens wearers (P = 0.028).
      Patients with low visual acuity (logMAR > 0.4) in the better eye had lower
      distance vision, social functioning, mental health, and role difficulties.
      Meanwhile, patients with low visual acuity (logMAR > 0.4) in the worse eye had
      lower general health scores (P < 0.05). Conclusions. Vision related quality of
      life was worse in keratoconus patients. Success in the contact lens usage and
      maintaining higher visual acuity may improve vision related quality of life. 

PMID- 24868456
TI  - Long term followup of photorefractive keratectomy with adjuvant use of mitomycin
      C.
AB  - Purpose. To study the long term refractive and visual outcomes of photorefractive
      keratectomy (PRK) with intraoperative application of mitomycin C (MMC). Methods.
      This study included 37 eyes who received myopic PRK; after photoablation, a
      sponge soaked in 0.02% MMC solution was applied in all corneas for 2 minutes.
      Efficacy, safety, predictability, and stability of PRK MMC were evaluated.
      Endothelial cell density was evaluated at the last postoperative interval.
      Results. Mean preoperative spherical equivalent (SEQ) was -6.03 +/- 1.87 D
      (diopters) and reduced to -0.09 +/- 0.53 D at the last postoperative examination.
      Mean followup was 44.73 +/- 18.24 months. All the eyes were in the +/-1.00 D of
      attempted versus achieved SEQ at the one-year follow-up interval. Furthermore,
      95% of the eyes did not lose lines or gained 1 to 2 lines of CDVA, while 5% lost
      1 line. At the third postoperative month, 89% of the eyes either were clear or
      had trace haze, while 4 eyes had mild haze; by the 12-month postoperative
      interval, none of the eyes demonstrated haze. Mean endothelial cell density (ECD)
      at the last postoperative interval was 2658 +/- 153 cells/mm(2). Conclusions.
      PRK, with intraoperative use of MMC, demonstrates stable refractive and visual
      outcomes up to 44 months after surgery. 

PMID- 24868457
TI  - Nd:YAG Capsulotomy after Phacoemulsification in Vitrectomized Eyes: Effects of
      Pars Plana Vitrectomy on Posterior Capsule Opacification.
AB  - To compare the progression of posterior capsule opacification (PCO) in patients
      who required Nd:YAG laser capsulotomy following either combined cataract surgery
      with pars plana vitrectomy (PPV; C-CV), sequential cataract surgery after PPV (S
      CV), or cataract surgery alone (CA). The medical records of 321 patients (408
      eyes) who underwent Nd:YAG capsulotomy were retrospectively evaluated. The CA
      group had a significantly longer time interval from cataract surgery to
      capsulotomy than that of both the CV group (P = 0.006) and the S-CV (P = 0.013)
      and C-CV (P = 0.042) subgroups when age-matched comparisons were used. CV
      patients who implanted a hydrophobic acrylic IOL had shorter time intervals than
      those of CA patients (P = 0.028). CV patients had larger hazard of earlier
      capsulotomy than CA patients (hazard ratio (HR) = 1.337; 95% confidence interval
      (CI) 1.100-1.625; P = 0.004). C-CV and S-CV patients both had larger hazard than
      CA patients in earlier capsulotomy (HR = 1.304; 95% CI = 1.007-1.688; P = 0.044,
      HR = 1.361; 95%  CI = 1.084-1.709; P = 0.008, resp.). PCO progresses more rapidly
      in patients undergoing combined or sequential cataract surgery and PPV than in
      patients undergoing CA. 

PMID- 24868458
TI  - A 2-Year, Phase IV, Multicentre, Observational Study of Ranibizumab 0.5 mg in
      Patients with Neovascular Age-Related Macular Degeneration in Routine Clinical
      Practice: The EPICOHORT Study.
AB  - Purpose. To assess the safety profile of ranibizumab 0.5 mg in patients with
      neovascular age-related macular degeneration (nAMD) in routine clinical practice.
      Methods. This 2-year, multicentre, observational study was conducted to capture
      real-world early practice and outcomes across Europe, shortly after European
      licensing of ranibizumab for nAMD. Being observational in nature, the study did
      not impose diagnostic/therapeutic interventions/visit schedule. Patients were to
      be treated as per the EU summary of product characteristics (SmPC) in effect
      during the study. Key outcome measures were incidence of selected adverse events
      (AEs), treatment exposure, bilateral treatment, compliance to the EU SmPC, and
      best-corrected visual acuity (BCVA) over 2 years. Results. 755 of 770 patients
      received treatment. Ranibizumab was generally well tolerated with low incidence
      of selected AEs (0%-1.9%). Patients received 6.2 (mean) injections and 133
      patients received bilateral treatment over 2 years. Protocol deviation to
      treatment compliance was reported in majority of patients. The observed decline
      in mean BCVA (Month 12, +1.5; Month 24, -1.3 letters) may be associated with
      undertreatment as suggested by BCVA subgroup analysis. Conclusion. The EPICOHORT
      study conducted in routine clinical practice reinforces the well-established
      safety profile of ranibizumab in nAMD. In early European practice it appeared
      that the nAMD patients were undertreated. 

PMID- 24868459
TI  - Evaluation of the Macular, Peripapillary Nerve Fiber Layer and Choroid Thickness
      Changes in Behcet's Disease with Spectral-Domain OCT.
AB  - Purpose. To assess the macular, choroid, and peripapillary nerve fiber layer
      thickness (RNFL) in Behcet's disease (BD) patients with and without ocular
      involvement by means of optical coherence tomography (OCT) and compare these
      findings with healthy controls. Design. Eighty patients with BD and 40 healthy
      controls who were followed up at the Uveitis and Retina Clinic of the Kayseri
      Research and Education Hospital in Turkey were enrolled in this prospective
      study. Subjects and Controls. The patients with BD were divided into two groups
      according to the presence of ocular involvement. Group 1 consisted of 40 eyes of
      40 patients with ocular involvement and group 2 consisted of 40 eyes of 40
      patients without ocular involvement. Methods. All of the patients and controls
      underwent macular, choroid, and peripapillary nerve fiber layer thickness
      analysis with Spectralis domain OCT (Spectralis OCT Heidelberg Engineering,
      Dossenheim, Germany). Main Outcome Measures. The differences in macular, choroid,
      and peripapillary nerve fiber layer thicknesses between groups were analyzed
      statistically. Results. Macular thickness was thinner in patients with BD than in
      the control group; this result was statistically significant (P = 0.05). There
      was no statistically significant difference in thickness between RNFL analysis of
      the patients with BD and control subjects. However, the BD patients with ocular
      involvement had statistically significant thinning in RNFL compared with BD
      patients without ocular involvement. Although the choroid was thicker in patients
      with BD than in the control group, it did not reach a statistically significant
      level (P = 0.382). Conclusions. BD with ocular involvement may be associated with
      decreased macular and RNFL thickness measured with spectral-domain OCT. 

PMID- 24868460
TI  - Platelet Consumption and Filter Clotting Using Two Different Membrane Sizes
      during Continuous Venovenous Haemodiafiltration in the Intensive Care Unit.
AB  - Background. The aim of this study was to investigate whether different
      haemofilter surface areas affect clotting and platelet consumption in critically
      ill patients undergoing continuous venovenous haemodiafiltration (CVVHDF).
      Methods. CVVHDF was performed in postdilution technique using a capillary
      haemofilter with two different membrane sizes, Ultraflux AV 1000S (n = 17,
      surface 1.8 m(2), volume 130 mL), and the smaller AV 600S (n = 16, surface 1.4
      m(2), volume 100 mL), respectively. Anticoagulation was performed with heparin.
      Results. No significant differences were found when the two filters were
      compared. CVVHDF was performed for 33 (7-128) hours with the filter AV 1000S and
      39 (7-97) hours with AV 600S (P = 0.68). Two (1-4) filters were utilised in both
      groups over this observation period (P = 0.94). Platelets dropped by 52,000 (0
      212,000) in AV 1000S group and by 89,500 (0-258,000) in AV 600S group (P = 0.64).
      Haemoglobin decreased by 1.2 (0-2.8) g/dL in AV 1000S group and by 1.65 (0-3.9)
      g/dL in AV 600S group (P = 0.51), leading to the transfusion of 1 (0-4) unit of
      blood in 19 patients (10 patients with AV 1000S and 9 with AV 600S). Filter
      observation was abandoned due to death (12.1%), need for systemic anticoagulation
      (12.1%), repeated clotting (36.4%), and recovery of renal function (39.4%).
      Conclusion. Our study showed that a larger filter surface area did neither reduce
      the severity of thrombocytopenia and anaemia, nor decrease the frequency of
      clotting events. 

PMID- 24868461
TI  - Childhood Adversities are Associated with Diabetes Management in Working Age in
      Finland.
AB  - Backgrounds. Research findings suggest that the mind can cause physical disease.
      To plan the best quality of care, general practitioner needs to understand an
      individual's health problems in physical, social, and psychological dimensions.
      This study sought to establish whether adverse life events occurring in childhood
      and adolescence are associated with diabetes. Methods. The cohort was collected
      from the health and social support (HeSSup) study-a postal follow-up survey of
      randomized working-aged Finns initiated in 1998. The response rate was 40.0% and
      the final cohort size 24057. Data on reimbursed diabetes medication during the
      years 1998-2006 were obtained from the Social Insurance Institute of Finland
      registers. Subjects were divided into insulin, tablet, combination therapy, and
      drug-naive groups together with a control group without diabetes. The prevalence
      of childhood adversities was assessed based on answers to six survey questions.
      Results. Childhood adversities showed predominant linkage to diabetes type 2
      groups, especially to the combination therapy group requiring combined insulin
      and tablet treatment. No connection was found between childhood adversities and
      insulin use. Cumulative adversities did not markedly increase the association.
      Conclusions. Stressful events in childhood are associated with diabetes
      combination therapy in working age. The meaning of the relationship remains
      unsolved. 

PMID- 24868462
TI  - Expression of tight junction protein claudin-1 in human crescentic
      glomerulonephritis.
AB  - The origin of crescent forming cells in human glomerulonephritis (GN) remains
      unknown. Some animal studies demonstrated that parietal epithelial cells of
      Bowman's capsule (PECs) were the main component of proliferating cells and PEC
      specific tight junction protein claudin-1 was expressed in crescentic lesions. We
      investigated the expression of claudin-1 in human GN. Immunohistochemistry for
      claudin-1 was performed on 17 kidney biopsy samples with crescent formation.
      Colocalization of claudin-1 with intracellular tight junction protein ZO-1 was
      also evaluated by immunofluorescence double staining. Claudin-1 is expressed
      mainly at the cell to cell contact site of proliferating cells in cellular
      crescentic lesions in patients with these forms of human GN. Small numbers of
      crescent forming cells showed extrajunctional localization of claudin-1.
      Colocalization of claudin-1 with ZO-1 was found at cell to cell contact sites of
      adjacent proliferating cells. In control samples, staining of claudin-1 was
      positive in PECs, but not in podocytes. Our findings suggest that claudin-1
      contributes to crescent formation as a component of the tight junction protein
      complex that includes ZO-1. Co-localization of claudin-1 with ZO-1 implies the
      formation of functional tight junction complexes in crescentic lesions to prevent
      the interstitial damage caused by penetration of filtered molecules from Bowman's
      space. 

PMID- 24868463
TI  - Comparison of CKD-EPI Cystatin C and Creatinine Glomerular Filtration Rate
      Estimation Equations in Asian Indians.
AB  - Background. Chronic kidney disease (CKD) is identified in the general population
      using estimated glomerular filtration rates (eGFR) calculated from a serum
      creatinine-based equation, the chronic kidney disease-epidemiology collaboration
      (CKD-EPI) equation. Using serum cystatin C in combination may improve eGFR
      accuracy. We evaluated the new CKD-EPI equations incorporating cystatin C in a
      population of Asian Indians in classifying CKD across body mass index, diabetes,
      and hypertension status. Methods. We retrieved standardized serum creatinine and
      serum cystatin C data from a cohort of 2877 Asian Indians aged 40-80 years from
      the Singapore Indian Eye Study and calculated eGFR (in mL/min/1.73 m(2)) with the
      new CKD-EPI equations and serum creatinine only equation. Results. The creatinine
      only equation mean eGFR (88 +/- 17) was similar to using spline Log cystatin C
      (88 +/- 22). The lowest mean eGFR (81 +/- 21) was obtained with the spline Log
      cystatin C-age, sex, and weight equation. The creatinine only equation had the
      fewest participants (7.1%) with eGFR <60 and spline Log cystatin C-age, sex, and
      weight equation had the most (16.1%). Conclusions. Using serum cystatin C
      resulted in widely varying eGFR which significantly affected the classification
      of chronic kidney disease. 

PMID- 24868464
TI  - Enhanced Photosynthesis and Carbon Metabolism Favor Arsenic Tolerance in
      Artemisia annua, a Medicinal Plant as Revealed by Homology-Based Proteomics.
AB  - This paper provides the first proteomic evidence of arsenic (As) tolerance and
      interactive regulatory network between primary and secondary metabolism in the
      medicinal plant, Artemisia annua. While chlorophyll fluorescence and
      photosynthetic rate depicted mild inhibition, there was a significant enhancement
      in PSI activity, whole chain, ATP, and NADPH contents in 100  MU M As treatments
      compared to the control plants. However, a decrease in the above variables was
      recorded under 150  MU M treatments. Proteomic decoding of the survival strategy
      of A. annua under As stress using 2-DE followed by MALDI-MS/MS revealed a total
      of 46 differentially expressed protein spots. In contrast to other plants where
      As inhibits photosynthesis, A. annua showed appreciable photosynthetic CO2
      assimilation and allocation of carbon resources at 100  MU M As concentration.
      While an increased accumulation of ATP synthase, ferredoxin-NADP(H)
      oxidoreductase, and FeS-rieske proteins supported the operation of cyclic
      electron transport, mdr ABC transporter protein and pcs gene might be involved in
      As detoxification. The most interesting observation was an increased accumulation
      of LEAFY like novel protein conceivably responsible for an early onset of
      flowering in A. annua under As stress. This study not only affirmed the role of
      energy metabolism proteins but also identified potential candidates responsible
      for As tolerance in plants. 

PMID- 24868465
TI  - Effects of a new patient safety-driven oxytocin dosing protocol on postpartum
      hemorrhage.
AB  - Objective. To determine if there was an increase in postpartum (PP) hemorrhage
      after decreasing the PP oxytocin dose from 40 to 30 units. Study Design.
      Retrospective cohort study comparing 8 months before to 8 months after the
      change. PP day 1 hemoglobin was subtracted from admission hemoglobin. Mean change
      was compared by Student's t-test. The best fit polynomial was analyzed for trends
      between the two time frames. Women who received blood transfusions were excluded.
      Results. 73/3564 (2.0%) women received blood transfusions in the pre group and
      64/3295 (1.9%) women in the post group, P = 0.8. Mean hemoglobin change +/-
      standard deviation was 1.53 +/- 0.03 g/dL for pre versus 1.52 +/- 0.05 g/dL for
      post, P = 0.68. 1003/3114 (32.2%) in the pre group had a hemoglobin decrease of
      >=2 g/dL compared to 918/2895 (31.7%) in the post group, P = 0.7. 261/3114 (8.4%)
      in the pre group had a hemoglobin decrease of >=3 g/dL compared to 252/2895
      (8.7%), P = 0.7. There were no significant trends between the two time frames.
      Conclusion. The change in the dose of PP oxytocin did not result in an increase
      in postpartum hemorrhage or an increase in the need for blood transfusion. 

PMID- 24868466
TI  - Expectant management of miscarriage in view of NICE Guideline 154.
AB  - Objective. To find out the success rate of conservative management of complete
      two weeks for miscarriage in view of NICE Guideline 154. Design. Prospective
      observational study. Setting. Early pregnancy assessment units of District
      General Hospital in the United Kingdom. Participants. Women of less than 14
      weeks' gestation, with a diagnosis of miscarriage (missed miscarriage/anembryonic
      or incomplete miscarriage). Interventions. Expectant management for two weeks.
      Main Outcome Measure. (1) Efficacy of 2-week expectant management, that is,
      complete resolution of miscarriage based either on self-reporting of patient
      after passing products of conception at home between D0 and D14 of expectant
      management or confirmation on scan at D14, and (2) short-term complications
      needing strong analgesia, blood transfusion, and antibiotics. Results. Expectant
      management of miscarriage for 2 weeks from the day of diagnosis was successful in
      58% (64 /111) and failed in 42% (47/111). Conclusions. Expectant management
      success rate is consistent with the results from the longitudinal studies and
      RCTs published in the past. It is a safe option as none of the patients on
      expectant/medical management needed strong analgesia/antibiotics or blood
      transfusion. 

PMID- 24868467
TI  - Evaluating Cytotoxicity of Hyaluronate Targeted Solid Lipid Nanoparticles of
      Etoposide on SK-OV-3 Cells.
AB  - The epithelial ovarian carcinoma is one of the most fatal gynecological cancers.
      Etoposide is used in treating platinum-resistant ovarian cancer. Sodium
      hyaluronate is a substance that binds to the CD44 receptors overexpressed in SK
      OV-3 cells of epithelial ovarian carcinoma. The aim of the present work was to
      study the cytotoxicity effect of hyaluronate targeted solid lipid nanoparticles
      (SLNs) of etoposide on SK-OV-3 cells. The cytotoxicity of the targeted and
      nontargeted SLNs of etoposide was compared to free drug on the SK-OV-3 cells by
      MTT assay method. The cellular uptake of the targeted and nontargeted
      nanoparticles containing sodium fluorescein was also studied. The difference of
      cell vitality between nontargeted nanoparticles and also targeted nanoparticles
      with free drug was significant. Targeted nanoparticles also caused more toxicity
      than nontargeted nanoparticles (P < 0.05). After 4 hours of incubating, the
      fluorescence was remarkably higher in the cells treated by targeted SLNs rather
      than nontargeted ones, and there was no observable fluorescence in cells
      incubated with pure sodium fluorescein. Hyaluronate targeted SLNs containing
      etoposide increased the cytotoxicity of etoposide on SK-OV-3 cells which may be a
      worthwhile potential method for reducing the prescribed dose and systemic side
      effects of this drug in epithelial ovarian carcinoma. 

PMID- 24868468
TI  - Increased aPKC Expression Correlates with Prostatic Adenocarcinoma Gleason Score
      and Tumor Stage in the Japanese Population.
AB  - Background. Levels of the protein kinase aPKC have been previously correlated
      with prostate cancer prognosis in a British cohort. However, prostate cancer
      incidence and progression rates, as well as genetic changes in this disease, show
      strong ethnic variance, particularly in Asian populations. Objective. The aim of
      this study was to validate association of aPKC expression with prostatic
      adenocarcinoma stages in a Japanese cohort. Methods. Tissue microarrays
      consisting of 142 malignant prostate cancer cases and 21 benign prostate tissues
      were subject to immunohistological staining for aPKC. aPKC staining intensity was
      scored by three independent pathologists and categorized as absent (0), dim (1+),
      intermediate (2+), and bright (3+). aPKC staining intensities were correlated
      with Gleason score and tumor stage. Results. Increased aPKC staining was observed
      in malignant prostate cancer, in comparison to benign tissue. Additionally, aPKC
      staining levels correlated with Gleason score and tumor stage. Our results extend
      the association of aPKC with prostate cancer to a Japanese population and
      establish the suitability of aPKC as a universal prostate cancer biomarker that
      performs consistently across ethnicities. 

PMID- 24868469
TI  - Parametric Optimization of Cultural Conditions for Carboxymethyl Cellulase
      Production Using Pretreated Rice Straw by Bacillus sp. 313SI under Stationary and
      Shaking Conditions.
AB  - Carboxymethyl cellulase (CMCase) provides a key opportunity for achieving
      tremendous benefits of utilizing rice straw as cellulosic biomass. Out of total
      80 microbial isolates from different ecological niches one bacterial strain,
      identified as Bacillus sp. 313SI, was selected for CMCase production under
      stationary as well as shaking conditions of growth. During two-stage
      pretreatment, rice straw was first treated with 0.5 M KOH to remove lignin
      followed by treatment with 0.1 N H2SO4 for removal of hemicellulose. The maximum
      carboxymethyl cellulase activity of 3.08 U/mL was obtained using 1% (w/v)
      pretreated rice straw with 1% (v/v) inoculum, pH 8.0 at 35 degrees C after 60 h
      of growth under stationary conditions, while the same was obtained as 4.15 U/mL
      using 0.75% (w/v) pretreated substrate with 0.4% (v/v) inoculum, pH 8.0 at 30
      degrees C, under shaking conditions of growth for 48 h. For maximum titre of
      CMCase carboxymethyl cellulose was optimized as the best carbon source under both
      cultural conditions while ammonium sulphate and ammonium nitrate were optimized
      as the best nitrogen sources under stationary and shaking conditions,
      respectively. The present study provides the useful data about the optimized
      conditions for CMCase production by Bacillus sp. 313SI from pretreated rice
      straw. 

PMID- 24868471
TI  - Targeting interleukin-4 receptor alpha by hybrid Peptide for novel biliary tract
      cancer therapy.
AB  - It is known that the interleukin-4 receptor alpha (IL-4R alpha ) is highly
      expressed on the surface of various human solid tumors. We previously designed
      novel IL-4R alpha -lytic hybrid peptide composed of binding peptide to IL-4R
      alpha and cell-lytic peptide and reported that the designed IL-4R alpha -lytic
      hybrid peptide exhibited cytotoxic and antitumor activity both in vitro and in
      vivo against the human pancreatic cancer cells expressing IL-4R alpha . Here, we
      evaluated the antitumor activity of the IL-4R alpha -lytic hybrid peptide as a
      novel molecular targeted therapy for human biliary tract cancer (BTC). The IL-4R
      alpha -lytic hybrid peptide showed cytotoxic activity in six BTC cell lines with
      a concentration that killed 50% of all cells (IC50) as low as 5  MU M. We also
      showed that IL-4R alpha -lytic hybrid peptide in combination with gemcitabine
      exhibited synergistic cytotoxic activity in vitro. In addition, intravenous
      administration of IL-4R alpha -lytic hybrid peptide significantly inhibited tumor
      growth in a xenograft model of human BTC in vivo. Taken together, these results
      indicated that the IL-4R alpha -lytic hybrid peptide is a potent agent that might
      provide a novel therapy for patients with BTC. 

PMID- 24868472
TI  - A case of comorbid myxoma and chronic lymphocytic leukemia: not just a
      coincidence?
AB  - Background. It is unclear why cardiac myxomas develop. We describe a case of
      comorbid myxoma and chronic lymphocytic leukemia (CLL) to offer insights into the
      tumor's pathophysiology. Case. A 56-year-old female with recurrent venous
      thromboembolism developed embolic stroke. Transesophageal echocardiogram showed a
      1.7 * 1 cm sessile left atrial mass at the interatrial septum. Histopathology
      revealed myxoma with a B cell lymphocytic infiltrate suggestive of a low grade
      lymphoproliferative disorder. Bone marrow biopsy and flow cytometry of blood and
      the cardiac infiltrate supported the diagnosis of atypical CLL. She was followed
      clinically in the absence of symptoms, organ infiltration, or cytopenia. After
      eighteen months, she developed cervical and axillary lymphadenopathy. Biopsy
      confirmed B cell CLL/small lymphocytic lymphoma. She elected to undergo
      chemotherapy with fludarabine, cyclophosphamide, and rituximab, with clinical
      remission. Conclusions. The coexistence of two neoplastic processes may be
      coincidental, but the cumulative likelihood is estimated at 0.002 per billion
      people per year. A shared pathogenic mechanism is more likely. Possibilities
      include chronic inflammation, vascular endothelial growth factor A, shared
      genetic mutations, changes in posttranslational regulation, or alterations in
      other cellular signaling pathways. Additional studies could expand our current
      understanding of the molecular biology of both myxomas and CLL. 

PMID- 24868473
TI  - Huge cavernous hemangiomas enveloping the optic nerve successfully removed by a
      vertical lid split orbitotomy.
AB  - A 63-year-old woman presented with a 15-year history of gradually increasing
      proptosis of right eye. Ocular examination revealed proptosis of 9 mm with
      decreased visual acuity in her right eye. CT scan showed a well-circumscribed and
      enhancing orbital mass filling almost the entire right orbit. The tumor occupied
      the superolateral, superomedial, and inferomedial intraconal space, enveloping
      the optic nerve. Complete excision of two large intraconal tumors was performed
      successfully via a vertical lid split orbitotomy. Histopathologic examination
      confirmed the diagnosis of cavernous hemangioma. There were no intraoperative or
      postoperative complications. The patient achieved a satisfactory cosmetic outcome
      1 year after surgery. 

PMID- 24868470
TI  - New Insights into the Pathogenesis of Alcohol-Induced ER Stress and Liver
      Diseases.
AB  - Alcohol-induced liver disease increasingly contributes to human mortality
      worldwide. Alcohol-induced endoplasmic reticulum (ER) stress and disruption of
      cellular protein homeostasis have recently been established as a significant
      mechanism contributing to liver diseases. The alcohol-induced ER stress occurs
      not only in cultured hepatocytes but also  in vivo  in the livers of several
      species including mouse, rat, minipigs, zebrafish, and humans. Identified causes
      for the ER stress include acetaldehyde, oxidative stress, impaired one carbon
      metabolism, toxic lipid species, insulin resistance, disrupted calcium
      homeostasis, and aberrant epigenetic modifications. Importance of each of the
      causes in alcohol-induced liver injury depends on doses, duration and patterns of
      alcohol exposure, genetic disposition, environmental factors, cross-talks with
      other pathogenic pathways, and stages of liver disease. The ER stress may occur
      more or less all the time during alcohol consumption, which interferes with
      hepatic protein homeostasis, proliferation, and cell cycle progression promoting
      development of advanced liver diseases. Emerging evidence indicates that long
      term alcohol consumption and ER stress may directly be involved in hepatocellular
      carcinogenesis (HCC). Dissecting ER stress signaling pathways leading to
      tumorigenesis will uncover potential therapeutic targets for intervention and
      treatment of human alcoholics with liver cancer. 

PMID- 24868474
TI  - Subconjunctival and orbital silicone oil granuloma (siliconoma) complicating
      intravitreal silicone oil tamponade.
AB  - A 30-year-old male, who underwent previous pars plana vitrectomy and silicone oil
      tamponade due to endogenous endophthalmitis originated from Klebsiella liver
      abscess, was referred for evisceration. At 2 months after vitrectomy with silicon
      oil tamponade, conjunctival chemosis and ocular pain were aggravated. Diffuse
      eyelid swelling and large subconjunctival mass with lipid droplets were noted. On
      MRI examination, subconjunctival mass and intra- and extraconal orbital mass
      around superior rectus muscle were observed. Excision of subconjunctival and
      orbital mass was performed. Histopathologic examination showed multiple silicone
      oil vacuoles surrounded by foreign body giant cells and fibrosis, which confirmed
      silicone oil granuloma. In a patient with suspicious melting sclera in diseases
      such as endophthalmitis, large silicone oil granuloma may be complicated in a
      rapid fashion after intravitreal silicone oil tamponade due to silicone oil
      leakage. 

PMID- 24868475
TI  - Isolated enteric cyst in the neck.
AB  - We report an extremely rare case of isolated enteric cyst in the neck region
      which was diagnosed on the histopathological examination. It was suspected to be
      duplication cyst on radiology. We have also evaluated the differential diagnosis
      and management issues. 

PMID- 24868476
TI  - A pitfall in transrectal prostate biopsy: malakoplakia evaluation of two cases
      based on the literature review.
AB  - Malakoplakia is a rarely seen inflammatory condition that is considered to
      develop secondary to a chronic Escherichia coli infection. Although malakoplakia
      usually affects the genitourinary tract, it may also be observed in the colon,
      stomach, lungs, liver, bones, uterus, and skin. Malakoplakia of the genitourinary
      system usually involves the bladder, whereas it may also affect the prostate
      along with the bladder. Malakoplakia of the prostate is very rare, and it may be
      clinically mistaken for prostatic malignancies. Definitive diagnosis is only
      possible through histopathological examination. This study elaborates on two
      patients who presented to our hospital in 2013 with high PSA levels. The primary
      clinical consideration was prostate carcinoma. However, these two cases were
      diagnosed as malakoplakia based on the results of histopathological analysis of
      the transrectal prostate biopsy specimen. 

PMID- 24868477
TI  - Extranodal Marginal Zone Lymphoma Presenting within the Meckel Diverticulum as
      Diverticulitis: A Case Report.
AB  - Meckel diverticulum is the most common congenital defect of the gastrointestinal
      tract. It can be asymptomatic or mimic appendicitis and may be complicated by
      bleeding, diverticulitis, obstruction, and, rarely, neoplasia. We report the
      first case of extranodal marginal zone lymphoma occupying a Meckel diverticulum.
      A 44-year-old man with history of colonic diverticulitis presented to the
      emergency department for evaluation of acute abdominal pain. Radiography showed
      enteric obstruction, prompting diagnostic laparoscopy. Above the level of mid
      ileum an intact Meckel diverticulum was identified. Microscopy showed extensive
      infiltration of sheets of small lymphocytes with abundant cytoplasm (monocytoid B
      cells) prominently in submucosa and focally transmural involving serosal adipose
      tissue with multiple reactive germinal centers. The immunostains showed
      positivity for CD20, BCL-2, and CD43 (weak) and negativity for CD3, CD5, BCL-1,
      CD10, and BCL-6 in monocytoid B-cells. Fluorescence in situ hybridization studies
      revealed API2-MALT1 fusion signals consistent with t(11;18)(q21;q21), which
      confirmed the diagnosis of extranodal marginal zone lymphoma, also known as
      mucosa associated lymphoid tissue lymphoma. 

PMID- 24868478
TI  - Burkitt lymphoma of thyroid gland in an adolescent.
AB  - Burkitt Lymphoma is a highly aggressive form of non-Hodgkin's lymphoma that in
      nonendemic areas has abdominal primary sites. We report a very rare case of
      Burkitt lymphoma of the thyroid gland presenting as a rapidly growing thyroid
      swelling in a 14-year-old white Caucasian British male with no preexisting
      thyroid or medical problems. The diagnosis was confirmed by an open wedge biopsy
      following a fine needle aspiration. The patient was treated according to the
      Children's Cancer and Leukaemia Group guidelines for BL-Group B protocol and
      currently is in remission. 

PMID- 24868479
TI  - Regional Cerebral Blood-Flow with 99mTc-ECD Brain Perfusion SPECT in Landau
      Kleffner Syndrome: Report of Two Cases.
AB  - Landau-Kleffner syndrome (LKS) is a rare childhood disorder characterized by
      acquired aphasia and epilepsy. 99mTc-ECD SPECT imaging was performed in two right
      handed children with LKS. A relative decrease in perfusion was found in the left
      frontal-temporal cortices of both patients as well as in the left and right
      parietal cortices of one patient with aphasia, without clinical epilepsy. The
      degree of regional cerebral perfusion impairment did not correlate with the
      severity of the clinical and EEG abnormalities, but the area of hypoperfusion was
      compatible with the speech area of the brain. Overall, although asymmetrical
      temporoparietal perfusion appears as a common finding in LKS, SPECT findings in
      LKS alone cannot elucidate the pathogenic features of the disorder in the brain.
      Here, we present two cases of LKS in which we investigated SPECT perfusion scans.

PMID- 24868480
TI  - Circular Abscess Formation of the Inner Preputial Leaf as a Complication of a
      Penile Mondor's Disease: The First Case Report.
AB  - Introduction. Mondor's disease of the penis is an uncommon condition
      characterized by thrombosis or thrombophlebitis involving the superficial dorsal
      veins. An accompanied lymphangitis is discussed. There is typical self-limiting
      clinical course. Case Presentation. This paper firstly reports a secondary
      abscess formation of the preputial leaf two weeks after penile Mondor's disease
      and subcutaneous lymphangitis as complication of excessive sexual intercourse of
      a 44-year-old man. Sexual transmitted diseases could be excluded. Lesions healed
      up completely under abscess drainage, antibiotic, and anti-inflammatory
      medication. Conclusion. Previous reports in the literature include several
      entities of the penile Mondor's disease. Our patient is very unusual in that he
      presented with a secondary preputial abscess formation due to superficial
      thrombophlebitis, subcutaneous lymphangitis, and local bacterial colonisation.
      Abscess drainage plus antiphlogistic and antibiotic medication is the treatment
      of choice. 

PMID- 24868481
TI  - Mortality Trends in Patients Hospitalized with the Initial Acute Myocardial
      Infarction in a Middle Eastern Country over 20 Years.
AB  - We aimed to define the temporal trend in the initial Acute Myocardial Infarction
      (AMI) management and outcome during the last two decades in a Middle Eastern
      country. A total of 10,915 patients were admitted with initial AMI with mean age
      of 53 +/- 11.8 years. Comparing the two decades (1991-2000) to (2001-2010), the
      use of antiplatelet drugs increased from 84% to 95%, beta -blockers increased
      from 38% to 56%, and angiotensin converting enzyme inhibitors (ACEI) increased
      from 12% to 36% (P < 0.001 for all). The rates of PCI increased from 2.5% to
      14.6% and thrombolytic therapy decreased from 71% to 65% (P < 0.001 for all).
      While the rate of hospitalization with Initial MI increased from 34% to 66%, and
      the average length of hospital stay decreased from 6.4 +/- 3 to 4.6 +/- 3, all
      hospital outcomes parameters improved significantly including a 39% reduction in
      in-hospital Mortality. Multivariate logistic regression analysis showed that
      higher utilization of antiplatelet drugs, beta -blockers, and ACEI were the main
      contributors to better hospital outcomes. Over the study period, there was a
      significant increase in the hospitalization rate in patients presenting with
      initial AMI. Evidence-based medical therapies appear to be associated with a
      substantial improvement in outcome and in-hospital mortality. 

PMID- 24868483
TI  - Serum leptin concentrations in Turkish Parkinson's disease population.
AB  - Objectives. To investigate leptin levels and their relationship to body
      composition and demographic and clinical characteristics of Turkish patients with
      Parkinson's disease (PD). Patients and Methods. Forty eligible PD patients and 25
      healthy controls were included in the study. Body composition measurements
      (height, weight, waist circumference (WC), and body mass index (BMI)) of the
      whole sample and clinical findings of PD patients were evaluated in the on-state.
      A single 5 mL fasting blood sample was obtained from each participant in the
      morning. Severity of PD was evaluated using the Hoehn and Yahr scale and the
      Unified Parkinson's Disease Rating Scale. Results. The mean age of the patients
      and controls was 60.8 +/- 9.4 and 61.8 +/- 5.8 years, while the mean BMI was
      30.17 +/- 5.10 and 28.03 +/- 3.23 and the mean leptin levels were 6.8 +/- 6.9 and
      3.9 +/- 3.8 ng/mL, respectively. Only age and gender were correlated with leptin
      levels. There was a significant difference (P < 0.001) in leptin levels between
      male (3.6 +/- 3.1 ng/mL) and female (14.3 +/- 7.7 ng/mL) PD patients. Among the
      male PD patients, older age and higher BMI and WC values were associated with
      higher mean leptin levels. There was not any significant relationship between
      leptin levels and clinical findings in PD patients. Conclusion. These results may
      suggest that leptin levels have no determinative role in the follow-up of PD
      patients with regard to the severity and clinical prognosis of PD. 

PMID- 24868482
TI  - Electroencephalogram and Alzheimer's disease: clinical and research approaches.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder that is characterized by
      cognitive deficits, problems in activities of daily living, and behavioral
      disturbances. Electroencephalogram (EEG) has been demonstrated as a reliable tool
      in dementia research and diagnosis. The application of EEG in AD has a wide range
      of interest. EEG contributes to the differential diagnosis and the prognosis of
      the disease progression. Additionally such recordings can add important
      information related to the drug effectiveness. This review is prepared to form a
      knowledge platform for the project entitled "Cognitive Signal Processing Lab,"
      which is in progress in Information Technology Institute in Thessaloniki. The
      team tried to focus on the main research fields of AD via EEG and recent
      published studies. 

PMID- 24868485
TI  - Endoscopic ultrasonography: Challenges and opportunities in the developing world.
AB  - Endoscopic ultrasonography (EUS) has become a vital diagnostic modality for the
      evaluation of mediastinal lymphadenopathy, pancreatic cysts and masses, anorectal
      pathology, subepithelial gastrointestinal lesions, and for the staging of many
      gastrointestinal and pulmonary malignancies. Establishing a EUS program in a
      developing country presents many challenges. Doing so in Pakistan has led to the
      identification of the following challenges: initial investment, ongoing costs
      (particularly fine needle aspiration needle costs), awareness and cytopathology.
      Endoscopic ultrasonography has revolutionized aspects of the practice of
      gastroenterology and oncology in the West. This technique is becoming
      increasingly available in the developing world, where it poses unique challenges
      to its practice. These challenges include those relating to service initiation
      and maintenance costs, physician awareness, and on-site cytopathology access. If
      these issues are anticipated and addressed in ways appropriate to local
      circumstances, obstacles to the institution of EUS programs can be overcome. 

PMID- 24868484
TI  - Colonoscopy preparation-induced disorders in renal function and electrolytes.
AB  - Colonoscopy and flexible sigmoidoscopy are commonly used mainly for colon cancer
      screening and detection, but also in several other situations such as
      inflammatory bowel disease (for diagnosis and follow up) and gastrointestinal
      hemorrhage. Bowel cleansing preparations mainly include polyethylene glycol and
      oral sodium phosphate solutions, with the later being most frequently used due to
      better toleration from patients. Despite their favourable safety profile these
      agents have been associated with renal function deterioration and electrolyte
      disorders, some of which were serious or even fatal. The present paper discusses
      the complications associated with colonoscopy preparation agents. 

PMID- 24868486
TI  - Histamine2-receptor antagonists: Rapid development of tachyphylaxis with repeat
      dosing.
AB  - Histamine2-receptor antagonists (H2RAs) are available over-the-counter (OTC) for
      the treatment and prevention of heartburn, but more than occasional, single-dose
      use can lead to rapid development of tachyphylaxis. The aim of this review is to
      assess the published evidence regarding the development of tachyphylaxis with
      repeat usage of H2RAs. PubMed and SCOPUS were searched across all years to
      identify clinical studies that examined the development of tachyphylaxis with
      repeated dosing of H2RAs. Although a single (first) dose of an H2RA can be
      effective for controlling gastric acid and preventing or relieving food-related
      heartburn, numerous studies confirm that tachyphylaxis, also known as tolerance,
      is consistently detected at the first time point assessed after the first dose,
      including the second day and/or second dose. Even if symptom relief is achieved
      with an H2RA, it may be due to desensitization of the esophagus to acid exposure,
      potentially providing symptom relief without significantly decreasing esophageal
      acid exposure. When recommending OTC drugs for treatment of frequent heartburn,
      clinicians should be aware of the potential for rapid development of
      tachyphylaxis in patients who use H2RAs for 2 or more consecutive days. Even if
      symptom relief is achieved, it may be due to desensitization of the esophagus to
      acid by the H2RA, potentially providing symptom relief without significantly
      decreasing esophageal acid exposure. Other strategies, such as an OTC proton pump
      inhibitor, may be needed to optimize management of frequent heartburn. 

PMID- 24868490
TI  - EVS vs TIPS shunt for gastric variceal bleeding in patients with cirrhosis: A
      meta-analysis.
AB  - AIM: To evaluate the clinical effects of transjugular intrahepatic portosystemic
      shunt (TIPS) vs endoscopic variceal sclerotherapy (EVS) in the management of
      gastric variceal (GV) bleeding in terms of variceal rebleeding, hepatic
      encephalopathy (HE), and survival by meta-analysis. METHODS: Medline, Embase, and
      CNKI were searched. Studies compared TIPS with EVS in treating GV bleeding were
      identified and included according to our predefined inclusion criteria. Data were
      extracted independently by two of our authors. Studies with prospective
      randomized design were considered to be of high quality. Hazard ratios (HRs) or
      odd ratios (ORs) were calculated using a fixed-effects model when there was no
      inter-trial heterogeneity. Oppositely, a random-effects model was employed.
      RESULTS: Three studies with 220 patients who had at least one episode of GV
      bleeding were included in the present meta-analysis. The proportions of patients
      with viral cirrhosis and alcoholic cirrhosis were 39% (range 0%-78%) and 36%
      (range 12% to 41%), respectively. The pooled incidence of variceal rebleeding in
      the TIPS group was significantly lower than that in the EVS group (HR = 0.3,
      0.35, 95%CI: 0.17-0.71, P = 0.004). However, the risk of the development of any
      degree of HE was significantly increased in the TIPS group (OR = 15.97, 95%CI:
      3.61-70.68). The pooled HR of survival was 1.26 (95%CI: 0.76-2.09, P = 0.36). No
      inter-trial heterogeneity was observed among these analyses. CONCLUSION: The
      improved effect of TIPS in the prevention of GV rebleeding is associated with an
      increased risk of HE. There is no survival difference between the TIPS and EVS
      groups. Further studies are needed to evaluate the survival benefit of TIPS in
      cirrhotic patients with GV bleeding.

PMID- 24868488
TI  - Understanding and treating refractory constipation.
AB  - Chronic constipation is a frequently encountered disorder in clinical practice.
      Most constipated patients benefit from standard medical approaches. However,
      current therapies may fail in a proportion of patients. These patients deserve
      better evaluation and thorough investigations before their labeling as refractory
      to treatment. Indeed, several cases of apparent refractoriness are actually due
      to misconceptions about constipation, poor basal evaluation (inability to
      recognize secondary causes of constipation, use of constipating drugs) or
      inadequate therapeutic regimens. After a careful re-evaluation that takes into
      account the above factors, a certain percentage of patients can be defined as
      being actually resistant to first-line medical treatments. These subjects should
      firstly undergo specific diagnostic examination to ascertain the subtype of
      constipation. The subsequent therapeutic approach should be then tailored
      according to their underlying dysfunction. Slow transit patients could benefit
      from a more robust medical treatment, based on stimulant laxatives (or their
      combination with osmotic laxatives, particularly over the short-term),
      enterokinetics (such as prucalopride) or secretagogues (such as lubiprostone or
      linaclotide). Patients complaining of obstructed defecation are less likely to
      show a response to medical treatment and might benefit from biofeedback, when
      available. When all medical treatments prove to be unsatisfactory, other
      approaches may be attempted in selected patients (sacral neuromodulation, local
      injection of botulinum toxin, anterograde continence enemas), although with
      largely unpredictable outcomes. A further although irreversible step is surgery
      (subtotal colectomy with ileorectal anastomosis or stapled transanal rectal
      resection), which may confer some benefit to a few patients with refractoriness
      to medical treatments. 

PMID- 24868487
TI  - Use of thiopurines in inflammatory bowel disease: Safety issues.
AB  - Thiopurines are widely used for maintenance treatment of inflammatory bowel
      disease. Inter-individual variability in clinical response to thiopurines may be
      attributed to several factors including genetic polymorphisms, severity and
      chronicity of disease, comorbidities, duration of administration, compliance
      issues and use of concomitant medication, environmental factors and clinician and
      patient preferences. The purpose of this review is to summarise the current
      evidence on thiopurine safety and toxicity, to describe adverse drug events and
      emphasise the significance of drug interactions, and to discuss the relative
      safety of thiopurine use in adults, elderly patients, children and pregnant
      women. Thiopurines are safe to use and well tolerated, however dose adjustment or
      discontinuation of treatment must be considered in cases of non-response, poor
      compliance or toxicity. Drug safety, clinical response to treatment and short to
      long term risks and benefits must be balanced throughout treatment duration for
      different categories of patients. Treatment should be individualised and
      stratified according to patient requirements. Enzymatic testing prior to
      treatment commencement is advised. Surveillance with regular clinic follow-up and
      monitoring of laboratory markers is important. Data on long term efficacy, safety
      of thiopurine use and interaction with other disease modifying drugs are lacking,
      especially in paediatric inflammatory bowel disease. High quality, collaborative
      clinical research is required so as to inform clinical practice in the future. 

PMID- 24868491
TI  - Naturalistic Effects of Five Days of Bedtime Caffeine Use on Sleep, Next-Day
      Cognitive Performance, and Mood.
AB  - Background: Disruptive effects of caffeine on sleep have previously been
      reported, although measures of next-day mood and performance have rarely been
      included. The present study aims to evaluate the effects of caffeine on sleep and
      associated next-day effects in a naturalistic field setting. Methods: Nineteen
      participants (daily caffeine intake 0-141 mg), assessed as good sleepers, took
      part in a randomized, placebo-controlled, double-blind, 2-week crossover study to
      assess the effects of bedtime caffeine use (250 mg) on sleep and next-day
      cognitive performance and mood, which were assessed on a mobile phone in the
      morning and afternoon. Sleep was assessed objectively (actiwatch) and
      subjectively (sleep diary). Results: Caffeine's effects on sleep were largely
      restricted to the first day of administration, with actigraphically measured
      reduced sleep efficiency, increased activity score and fragmentation index,
      decreased self-rated sleep quality, and an increased occurrence of participants
      waking early; only decreased sleep efficiency remained over the week. Effects on
      next-day performance and mood were evident over the whole week, although despite
      disrupting sleep, accuracy on a working memory task was higher after caffeine
      than placebo administration. Conclusions: Caffeine disrupted sleep, although when
      assessing next-day performance, which may have been affected by the presence of
      residual caffeine, performance appeared better after caffeine compared to
      placebo, although this was most likely due to prevention of the effects of
      overnight withdrawal from caffeine rather than representing a net benefit.
      Furthermore, partial tolerance developed to the effects of caffeine on sleep.

PMID- 24868492
TI  - Eveningness Chronotype, Daytime Sleepiness, Caffeine Consumption, and Use of
      Other Stimulants Among Peruvian University Students.
AB  - Objectives: The aims of this study were to evaluate patterns of circadian
      preferences and daytime sleepiness, and to examine the extent to which the
      consumption of stimulant beverages is associated with daytime sleepiness and
      evening chronotype among Peruvian college-age students. Methods: A total of 2,581
      undergraduate students completed a self-administered comprehensive questionnaire
      that gathered information about sleep habits, sociodemographic and lifestyle
      characteristics, and the use of caffeinated beverages. The Morningness
      Eveningness Questionnaire (MEQ) and Epworth Sleepiness Scale (ESS) were used to
      assess chronotype and daytime sleepiness. We used multivariable linear and
      logistic regression procedures to estimate odds ratios (OR) and 95% confidence
      intervals (95% CI) for the associations of sleep disorders with sociodemographic
      and behavioral factors. Results: The prevalence of daytime sleepiness was 35%
      [95% CI 32.7-36.4] and eveningness chronotype was 10% [95% CI 8.8-11.1%]. Age,
      sex, cigarette smoking, and alcohol consumption were significantly associated
      with an evening chronotype. After adjusting for age, sex, smoking, body mass
      index, and physical activity, students who reported consumption of any stimulant
      beverages had 1.25 increased odds of excessive daytime sleepiness (OR=1.25 [95%
      CI 1.03-1.53]) compared with students who did not consume stimulant beverages.
      Consumption of any stimulant beverages was not statistically significantly
      associated with being an evening chronotype (OR=1.30 [95% CI 0.86-1.96]).
      Conclusions: Excessive daytime sleepiness and eveningness chronotype are common
      among Peruvian college students. MEQ scores were associated with age, sex,
      smoking, and alcohol consumption. Regular stimulant beverage consumption tended
      to be positively associated with excessive daytime sleepiness.

PMID- 24868489
TI  - Esophageal motility abnormalities in gastroesophageal reflux disease.
AB  - Esophageal motility abnormalities are among the main factors implicated in the
      pathogenesis of gastroesophageal reflux disease. The recent introduction in
      clinical and research practice of novel esophageal testing has markedly improved
      our understanding of the mechanisms contributing to the development of
      gastroesophageal reflux disease, allowing a better management of patients with
      this disorder. In this context, the present article intends to provide an
      overview of the current literature about esophageal motility dysfunctions in
      patients with gastroesophageal reflux disease. Esophageal manometry, by recording
      intraluminal pressure, represents the gold standard to diagnose esophageal
      motility abnormalities. In particular, using novel techniques, such as high
      resolution manometry with or without concurrent intraluminal impedance
      monitoring, transient lower esophageal sphincter (LES) relaxations, hypotensive
      LES, ineffective esophageal peristalsis and bolus transit abnormalities have been
      better defined and strongly implicated in gastroesophageal reflux disease
      development. Overall, recent findings suggest that esophageal motility
      abnormalities are increasingly prevalent with increasing severity of reflux
      disease, from non-erosive reflux disease to erosive reflux disease and Barrett's
      esophagus. Characterizing esophageal dysmotility among different subgroups of
      patients with reflux disease may represent a fundamental approach to properly
      diagnose these patients and, thus, to set up the best therapeutic management.
      Currently, surgery represents the only reliable way to restore the
      esophagogastric junction integrity and to reduce transient LES relaxations that
      are considered to be the predominant mechanism by which gastric contents can
      enter the esophagus. On that ground, more in depth future studies assessing the
      pathogenetic role of dysmotility in patients with reflux disease are warranted. 

PMID- 24868493
TI  - How long is enough to detect terrestrial animals? Estimating the minimum trapping
      effort on camera traps.
AB  - Camera traps is an important wildlife inventory tool for estimating species
      diversity at a site. Knowing what minimum trapping effort is needed to detect
      target species is also important to designing efficient studies, considering both
      the number of camera locations, and survey length. Here, we take advantage of a
      two-year camera trapping dataset from a small (24-ha) study plot in Gutianshan
      National Nature Reserve, eastern China to estimate the minimum trapping effort
      actually needed to sample the wildlife community. We also evaluated the relative
      value of adding new camera sites or running cameras for a longer period at one
      site. The full dataset includes 1727 independent photographs captured during
      13,824 camera days, documenting 10 resident terrestrial species of birds and
      mammals. Our rarefaction analysis shows that a minimum of 931 camera days would
      be needed to detect the resident species sufficiently in the plot, and c. 8700
      camera days to detect all 10 resident species. In terms of detecting a diversity
      of species, the optimal sampling period for one camera site was c. 40, or long
      enough to record about 20 independent photographs. Our analysis of evaluating the
      increasing number of additional camera sites shows that rotating cameras to new
      sites would be more efficient for measuring species richness than leaving cameras
      at fewer sites for a longer period. 

PMID- 24868496
TI  - Blood-brain barrier regulation: Environmental cues controlling the onset of
      barrier properties.
AB  - The existence of a barrier between the central nervous system (CNS) and the
      systemic circulation has been described over one hundred years ago. Since the
      discovery that this barrier was instigated by the barrier properties of the brain
      endothelial cells, research has focused on the identification of pathways how the
      brain endothelial cells are instructed to form the highly specialized blood-brain
      barrier (BBB). Even though our current understanding of BBB development is far
      from complete, recent literature shows a rise in knowledge of CNS-specific cues
      that can drive BBB development.   In this commentary, we will provide a brief
      overview of brain selective factors that are critical in the development of
      barrier properties in the brain endothelium; in particular the role of retinoic
      acid will be discussed. 

PMID- 24868494
TI  - Phosphatase regulation of intercellular junctions.
AB  - Intercellular junctions represent the key contact points and sites of
      communication between neighboring cells. Assembly of these junctions is
      absolutely essential for the structural integrity of cell monolayers, tissues and
      organs. Disruption of junctions can have severe consequences such as diarrhea,
      edema and sepsis, and contribute to the development of chronic inflammatory
      diseases. Cell junctions are not static structures, but rather they represent
      highly dynamic micro-domains that respond to signals from the intracellular and
      extracellular environments to modify their composition and function. This review
      article will focus on the regulation of tight junctions and adherens junctions by
      phosphatase enzymes that play an essential role in preserving and modulating the
      properties of intercellular junction proteins. 

PMID- 24868495
TI  - JNK is a novel regulator of intercellular adhesion.
AB  - c-Jun N-terminal Kinase (JNK) is a family of protein kinases, which are activated
      by stress stimuli such as inflammation, heat stress and osmotic stress, and
      regulate diverse cellular processes including proliferation, survival and
      apoptosis. In this review, we focus on a recently discovered function of JNK as a
      regulator of intercellular adhesion. We summarize the existing knowledge
      regarding the role of JNK during the formation of cell-cell junctions. The
      potential mechanisms and implications for processes requiring dynamic formation
      and dissolution of cell-cell junctions including wound healing, migration, cancer
      metastasis and stem cell differentiation are also discussed. 

PMID- 24868500
TI  - Celebrate participating in the PubMed Central.

PMID- 24868498
TI  - The role of Haptoglobin and its related protein, Zonulin, in inflammatory bowel
      disease.
AB  - Crohn's disease (CD) and ulcerative colitis (UC), collectively called
      inflammatory bowel disease (IBD), are immune-mediated conditions characterized by
      a chronic inflammation of the gut. Their precise etiology is unknown, although an
      increased intestinal permeability has been shown to play a central role in the
      pathogenesis of IBD. The intestinal epithelium provides the largest interface
      between the external environment and the host, and is thus a crucial regulation
      site of innate and adaptive immunity. Zonulin is one of the few known
      physiological mediators of paracellular intestinal permeability. It was found
      upregulated in different immune diseases like Celiac disease and Type 1 Diabetes
      (T1D). Recently, human zonulin was identified as prehaptoglobin-2 (pre-HP2) which
      before only had been regarded as the inactive precursor for HP2. Haptoglobin (HP)
      is a hemoglobin-binding protein with immunomodulatory properties. Its gene
      harbors a common polymorphism with 2 different alleles: HP1 and HP2. Allele HP2
      and genotype HP22 has been shown to be overrepresented in different immune
      diseases like Rheumatoid Arthritis (RA), Systemic Lupus Erythematosus (SLE) and
      T1D, and has also been found to be more frequent in patients with IBD (UC and CD)
      than in healthy controls.   In order to get some clues about the mechanism of
      action of HP(2) in IBD pathogenesis, we here review the current state of
      knowledge about zonulin and haptoglobin structure and function, and their
      plausible role in immune mediated diseases with an emphasis on IBD. 

PMID- 24868497
TI  - Small GTPases of the Ras superfamily regulate intestinal epithelial homeostasis
      and barrier function via common and unique mechanisms.
AB  - The intestinal epithelium forms a stable barrier protecting underlying tissues
      from pathogens in the gut lumen. This is achieved by specialized integral
      membrane structures such as tight and adherens junctions that connect neighboring
      cells and provide stabilizing links to the cytoskeleton. Junctions are constantly
      remodeled to respond to extracellular stimuli. Assembly and disassembly of
      junctions is regulated by interplay of actin remodeling, endocytotic recycling of
      junctional proteins, and various signaling pathways. Accumulating evidence
      implicate small G proteins of the Ras superfamily as important signaling
      molecules for the regulation of epithelial junctions. They function as molecular
      switches circling between an inactive GDP-bound and an active GTP-bound state.
      Once activated, they bind different effector molecules to control cellular
      processes required for correct junction assembly, maintenance and remodelling.
      Here, we review recent advances in understanding how GTPases of the Rho, Ras, Rab
      and Arf families contribute to intestinal epithelial homeostasis. 

PMID- 24868499
TI  - Pediatric lupus nephritis: Management update.
AB  - Childhood-onset systemic lupus erythematosus (cSLE) is a severe multisystem
      autoimmune disease. Renal involvement occurs in the majority of cSLE patients and
      is often fatal. Renal biopsy is an important investigation in the management of
      lupus nephritis. Treatment of renal lupus consists of an induction phase and
      maintenance phase. Treatment of childhood lupus nephritis using steroids is
      associated with poor outcome and excess side-effects. The addition of
      cyclophosphamide to the treatment schedule has improved disease control. In view
      of treatment failure using these drugs and a tendency for non-adherence, many
      newer agents such as immune-modulators and monoclonal antibodies are being tried
      in patients with cSLE. Trials of these novel agents in the pediatric population
      are still lacking making a consensus in the management protocol of pediatric
      lupus nephritis difficult. 

PMID- 24868502
TI  - Comparison of the reproducibility of results of a new peri-implantitis assessment
      system (implant success index) with the Misch classification.
AB  - OBJECTIVES: The present study was conducted to determine the reproducibility of
      peri-implant tissue assessment using the new implant success index (ISI) in
      comparison with the Misch classification. MATERIALS AND METHODS: In this
      descriptive study, 22 cases of peri-implant soft tissue with different conditions
      were selected, and color slides were prepared from them. The slides were shown to
      periodontists, maxillofacial surgeons, prosthodontists and general dentists, and
      these professionals were asked to score the images according to the Misch
      classification and ISI. The intra- and inter-observer reproducibility scores of
      the viewers were assessed and reported using kappa and weighted kappa (WK) tests.
      RESULTS: Inter-observer reproducibility of the ISI technique between the
      prosthodontists-periodontists (WK=0.85), prosthodontists-maxillofacial surgeons
      (WK=0.86) and periodontists-maxillofacial surgeons (WK=0.9) was better than that
      between general dentists and other specialists. In the two groups of general
      dentists and maxillofacial surgeons, ISI was more reproducible than the Misch
      classification system (WK=0.99 versus WK non-calculable, WK=1 and WK=0.86). The
      intra-observer reproducibility of both methods was equally excellent among
      periodontists (WK=1). For prosthodontists, the WK was not calculable via any of
      the methods. CONCLUSION: The intra-observer reproducibility of both the ISI and
      Misch classification techniques depends on the specialty and expertise of the
      clinician. Although ISI has more classes, it also has higher reproducibility than
      simpler classifications due to its ability to provide more detail.

PMID- 24868501
TI  - Current trends in dental implants.
AB  - Tooth loss is very a very common problem; therefore, the use of dental implants
      is also a common practice. Although research on dental implant designs, materials
      and techniques has increased in the past few years and is expected to expand in
      the future, there is still a lot of work involved in the use of better
      biomaterials, implant design, surface modification and functionalization of
      surfaces to improve the long-term outcomes of the treatment. This paper provides
      a brief history and evolution of dental implants. It also describes the types of
      implants that have been developed, and the parameters that are presently used in
      the design of dental implants. Finally, it describes the trends that are employed
      to improve dental implant surfaces, and current technologies used for the
      analysis and design of the implants. 

PMID- 24868504
TI  - A follow-up study on extracorporeal fixation of condylar fractures using vertical
      ramus osteotomy.
AB  - OBJECTIVES: The aim of this study is to report the results of extracorporeal
      fixation in patients with mandibular condylar fractures and compare them with the
      clinical results of conservative treatment. MATERIALS AND METHODS: The medical
      records of 92 patients (73 male [M] : 19 female [F], age 13-69 years, mean 33.1
      years) treated for condylar fractures at the Department of Oral and Maxillofacial
      Surgery in Sun Dental Hospital (Daejeon, Korea) from 2007 to 2012 were reviewed.
      Patients were divided into three groups: group A (23 patients; M : F=18 : 5, age
      21-69 years, mean 32.6 years), treated with extracorporeal fixation; group B (30
      patients; M : F=24 : 6, age 16-57 years, mean 21.1 years), treated by
      conventional open reduction; and group C (39 patients; M : F=31 : 8, age 16-63
      years, mean 34.4 years), treated with the conservative method ('closed'
      reduction). Clinical and radiographic findings were evaluated and analyzed
      statistically. RESULTS: Occurrence of postoperative condylar resorption
      correlated with certain locations and types of fracture. In this study, patients
      in group A (treated with extracorporeal fixation) did not demonstrate significant
      postoperative complications such as malocclusion, mandibular hypomobility,
      temporomandibular disorder, or complete resorption of condyle fragments.
      CONCLUSION: In superiorly located mandibular condyle fractures, exact
      reconstruction of condylar structure with the conventional open reduction
      technique can be difficult due to the limited surgical and visual fields. In such
      cases, extracorporeal fixation of the condyle using vertical ramus osteotomy may
      be a better choice of treatment because it results in anatomically accurate
      reconstruction and low risk of complications.

PMID- 24868503
TI  - The seven-year cumulative survival rate of Osstem implants.
AB  - OBJECTIVES: This study was performed to analyze the cumulative survival rate of
      Osstem implants (Osstem Implant Co., Ltd.) over a seven-year period. MATERIALS
      AND METHODS: A total of 105 patients who had 467 Osstem implants that were placed
      at the Section of Dentistry, Seoul National University Bundang Hospital
      (Seongnam, Korea) from June 2003 through December 2005 were analyzed. The life
      table method and a cross-tabulation analysis were performed to evaluate the
      cumulative survival rate. The log rank test was used to evaluate the survival
      curve. The influence that the prognostic factors had on the survival rate was
      determined with a Cox proportional hazard model based on logistic regression
      analysis [corrected]. RESULTS: The seven-year cumulative survival rate of Osstem
      implants was 95.37%. The Cox proportional hazard model revealed that the
      following factors had a significant influence on survival rate; increased
      diameter, reduced prosthetic loading period and performance of bone grafting.
      CONCLUSION: The osstem implants showed satisfactory results over the seven-year
      study period.

PMID- 24868505
TI  - Mandibular condyle and infratemporal fossa reconstruction using vascularized
      costochondral and calvarial bone grafts.
AB  - There are some difficulties in approaching and removing the lesion in
      infratemporal fossa because of its anatomical location. After wide excision of
      tumor lesion, it is also difficult for reconstruction of mandibular condyle and
      cranium base on infratemporal fossa. Besides, there are some possibilities of
      cerebrospinal fluid leakage, intracranial infection and bone resorption. It is
      also challenging for functional reconstruction that allows normal mandibular
      movement, preventing mandibular condyle from invaginating into the skull. In this
      report, we present 14-month follow-up results of a patient who had undergone
      posterior segmental mandibulectomy including condyle and infratemporal calvarial
      bone and mandible reconstruction with free vascularized costochondral rib and
      calvarial bone graft to restoration of the temporomandibular joint area. 

PMID- 24868506
TI  - Treatment of dental implant-related maxillary sinusitis with functional
      endoscopic sinus surgery in combination with an intra-oral approach.
AB  - The present report describes the case of a patient who underwent maxillary
      sinusitis right after dental implant installation with sinus lifting. Computed
      tomography scan revealed a dental implant (#16) was protruded inside the right
      maxillary sinus and confirmed the obstruction of ostium. A symptom remission was
      gained with the dual approaches combined by functional endoscopic sinus surgery
      and an intra-oral approach. Fully recovered function and healing of sinus were
      identified after 10 months follow-up. We report the case of sinusitis caused by
      protrusion of implants with sinus floor lift procedures and propose that
      practitioners should be aware of the possible its complications and management. 

PMID- 24868507
TI  - The treatment of malocclusion after open reduction of maxillofacial fracture: a
      report of three cases.
AB  - The posttraumatic complications of jaw fractures related to jaw function and
      facial deformity include nonunion, malunion, malocclusion, temporomandibular
      joint dysfunction and facial asymmetry. This report presents cases referred to
      our department for revision of malunion and malocclusion following inadequate
      reduction of jaw fractures. Three patients with posttraumatic malocclusions
      caused by malunion were treated with a LeFort I osteotomy in one case and re
      fracture in two cases. All of the patients exhibited stable results without
      further complications (e.g., malunion or malocclusion). Accurate preoperative
      diagnosis and proper anatomical reduction of the fracture segments are essential
      to preventing post-surgical malunion and malocclusion. 

PMID- 24868508
TI  - Commentary to "Survival rate of Astra Tech implants with maxiilary sinus lift".

PMID- 24868509
TI  - The current problem with journal review systems.

PMID- 24868510
TI  - Nutritional deficiencies in the pediatric age group in a multicultural developed
      country, Israel.
AB  - Nutrient deficiencies are prevalent worldwide. Diseases and morbid conditions
      have been described to result from nutritional deficiencies. It is essential to
      address nutrient deficiencies as these may lead to chronic long-term health
      problems such as rickets, iron deficiency anemia, goiter, obesity, coronary heart
      disease, type 2 diabetes, stroke, cancer and osteoporosis. In the present review
      we surveyed the extent and severity of nutritional deficiencies in Israel through
      a selective and comprehensive Medline review of previous reports and studies
      performed during the last 40 years. Israeli populations have multiple nutritional
      deficiencies, including iron, calcium, zinc, folic acid, and vitamins B12, C, D
      and E, spanning all age groups, several minorities, and specific regions. In
      Israel, some of the nutrients are mandatorily implemented and many of them are
      implemented voluntarily by local industries. We suggest ways to prevent and treat
      the nutritional deficiencies, as a step to promote food fortification in Israel. 

PMID- 24868512
TI  - Cesarean scar endometrioma: Case series.
AB  - AIM: To evaluate endometrioma located at cesarean scatrix. METHODS: Medical data
      of 6 patients who presented to our institution with abdominal wall endometrioma
      were evaluated retrospectively and reviewed literature in this case series. The
      diagnostic approaches and treatment is discussed. RESULTS: All patients had a
      painful mass located at abdominal scars with history of cesarean section. The
      ages ranged from 31 to 34 and Doppler ultrasonography (US) detected hypoechoic
      mass with a mean diameter of 30 mm. Initial diagnosis was endometrioma in 4 and
      incisional hernia in 2 of 6 patients. Treatment was achieved with surgical
      excision in 5 patients, and one is followed by hormone suppression therapy with
      gonadotropin. CONCLUSION: Malignant or benign tumors of abdominal wall and
      incisional hernias should be kept in mind for diagnosis of endometrioma. Imaging
      methods like doppler US, computed tomography and magnetic resonance imaging
      should be used for differential diagnosis. Definitive diagnosis can only be made
      histopathologically. The treatment should be complete surgical excision and take
      care against intraoperative auto-inoculation of endometrial tissue in order to
      prevent recurrences.

PMID- 24868511
TI  - Animal models of atherosclerosis.
AB  - In this mini-review several commonly used animal models of atherosclerosis have
      been discussed. Among them, emphasis has been made on mice, rabbits, pigs and non
      human primates. Although these animal models have played a significant role in
      our understanding of induction of atherosclerotic lesions, we still lack a
      reliable animal model for regression of the disease. Researchers have reported
      several genetically modified and transgenic animal models that replicate human
      atherosclerosis, however each of current animal models have some limitations.
      Among these animal models, the apolipoprotein (apo) E-knockout (KO) mice have
      been used extensively because they develop spontaneous atherosclerosis.
      Furthermore, atherosclerotic lesions developed in this model depending on
      experimental design may resemble humans' stable and unstable atherosclerotic
      lesions. This mouse model of hypercholesterolemia and atherosclerosis has been
      also used to investigate the impact of oxidative stress and inflammation on
      atherogenesis. Low density lipoprotein (LDL)-r-KO mice are a model of human
      familial hypercholesterolemia. However, unlike apo E-KO mice, the LDL-r-KO mice
      do not develop spontaneous atherosclerosis. Both apo E-KO and LDL-r-KO mice have
      been employed to generate other relevant mouse models of cardiovascular disease
      through breeding strategies. In addition to mice, rabbits have been used
      extensively particularly to understand the mechanisms of cholesterol-induced
      atherosclerosis. The present review paper details the characteristics of animal
      models that are used in atherosclerosis research. 

PMID- 24868513
TI  - Systematic review of noninvasive treatments to arrest dentin non-cavitated caries
      lesions.
AB  - AIM: To systematically review the literature on the efficacy of noninvasive
      methods of arresting the progression of non-cavitated occlusal carious lesions in
      dentin. METHODS: The Medline/PubMed, LILACS, SciELO and Scopus databases were
      searched to identify relevant publications through to November 2013. Only
      clinical trials evaluating the ability of noninvasive methods to arrest the
      progression of occlusal non-cavitated carious lesions in dentin were included.
      Screening, data extraction and quality assessment were conducted independently
      and in duplicate. RESULTS: Of 167 citations identified, nine full text articles
      were screened and five were included in the analysis. All papers reported on
      occlusal fissure sealing using a self-curing glass ionomer (n = 1) or resin-based
      (n = 4) sealant. Only the use of resin-based sealant to obliterate occlusal
      fissures arrested the progression of non-cavitated occlusal carious lesions in
      dentin. CONCLUSION: Occlusal fissure sealing with a resin-based sealant may
      arrest the progression of non-cavitated occlusal dentinal caries. Further
      clinical trials with longer follow-up times should be performed to increase
      scientific evidence.

PMID- 24868514
TI  - Atrium of stone: A case of confined left atrial calcification without hemodynamic
      compromise.
AB  - Dystrophic cardiac calcification is often associated with conditions causing
      systemic inflammation and when present, is usually extensive, often encompassing
      multiple cardiac chambers and valves. We present an unusual case of dystrophic
      left atrial calcification in the setting of end stage renal disease on
      hemodialysis diagnosed by echocardiography and computed tomography. Significant
      calcium deposition is confined within the walls of the left atrium with no
      involvement of the mitral valve, and no hemodynamic effects. 

PMID- 24868515
TI  - Primary colonic lymphoma: An incidental finding in a patient with a gallstone
      attack.
AB  - We report a case of primary colonic lymphoma incidentally diagnosed in a patient
      presenting a gallbladder attack making particular attention on the diagnostic
      findings at ultrasound (US) and total body computed tomography (CT) exams that
      allowed us to make the correct final diagnosis. A 85-year-old Caucasian male
      patient was referred to our department due to acute pain at the upper right
      quadrant, spreaded to the right shoulder blade. Patient had nausea and mild fever
      and Murphy's maneuver was positive. At physical examination a large bulky mass
      was found in the right flank. Patient underwent to US exam that detected a big
      stone in the lumen of the gallbladder and in correspondence of the palpable mass,
      an extended concentric thickening of the colic wall. CT scan was performed and
      confirmed a widespread and concentric thickening of the wall of the ascending
      colon and cecum. In addition, revealed signs of microperforation of the colic
      wall. Numerous large lymphadenopathies were found in the abdominal, pelvic and
      thoracic cavity and there was a condition of splenomegaly, with some ischemic
      outcomes in the context of the spleen. No metastasis in the parenchimatous organs
      were found. These imaging findings suggest us the diagnosis of lymphoma. Patient
      underwent to surgery, and right hemicolectomy and cholecystectomy was performed.
      Histological examination confirmed our diagnosis, revealing a diffuse large B
      cell lymphoma. The patient underwent to Cyclophosphamide, Hydroxydaunorubicin,
      Oncovin, Prednisone chemotherapy showing only a partial regression of the
      lymphadenopathies, being in advanced stage at the time of diagnosis. 

PMID- 24868516
TI  - Parathyroid carcinoma in pregnancy.
AB  - A 24-year-old female patient with parathyroid carcinoma, the rarest endocrine
      malignancy, had two pregnancies. In the first pregnancy, she had severe nausea
      and fatigue. Hypercalcemia and hyperparathyroidism were diagnosed in the
      postpartum period. Hyperemesis gravidarum masked a diagnosis of hypercalcemia.
      Neck ultrasound and Tc-99m sestamibi found an enlarged lower right parathyroid
      gland. The gland was surgically removed, and an initial pathology report
      described atypical adenoma. Shortly afterward, she became pregnant again. During
      the second pregnancy, her calcium level was frequently controlled but was always
      in the normal range. Normocalcemia is explained by the specific physiology of
      pregnancy accompanied by hemodilution, hypoalbuminemia and maternal
      hypercalciuria (mediated by increased glomerular filtration). During lactation,
      calcium levels rose, and a new neck ultrasound showed a solitary mass in the area
      of prior surgery and an enlarged pretracheal lymph node. Fine needle aspiration
      of the solitary mass and node showed parathyroid carcinoma cells. The tumor mass
      was resected en bloc with the contiguous tissues and surrounding lymph nodes
      (pathology report; parathyroid carcinoma with metastases). Over the next five
      years, four consecutive surgeries were performed to remove malignant parathyroid
      tissue, lymph nodes and local metastases. Following the surgical procedures, no
      hypocalcemia was observed. More serious hypercalcemia recurred; the calcium level
      was difficult to control with a combination of pamidronate, cinacalcet and loop
      diuretic. No elements of multiple endocrine neoplasia were present. 

PMID- 24868517
TI  - X-ray diagnosis with a bloating agent for foreign object ingestion.
AB  - The location of an ingested foreign object is often difficult to determine by X
      ray if gastric air bubbles are not clear in the image. Methods that provide
      negative contrast can facilitate precise object localization, which is important
      for object retrieval and treatment of the patient. This case report describes a
      male child, 2 years and 2 mo of age, who accidentally swallowed a lithium battery
      while playing at home. A plain X-ray showed that the battery was in the abdomen,
      but it was unclear whether the object was still inside the stomach. A second X
      ray examination performed after oral administration of a bloating agent to
      produce expansion of the stomach and provide negative contrast confirmed that the
      ingested battery was still in the stomach. The battery was then carefully removed
      using magnetic and balloon catheters under fluoroscopic guidance. This case
      report describes the successful use of an orally administered bloating agent
      without pain to the child in order to determine the precise location of a foreign
      object in the abdomen. 

PMID- 24868519
TI  - Pancreatic tuberculosis mimicking pancreatic carcinoma during anti-tuberculosis
      therapy: A case report.
AB  - Pancreatic tuberculosis (TB) is a rare condition, even in immunocompetent hosts.
      A case is presented of pancreatic TB that mimicked pancreatic head carcinoma in a
      40-year-old immunocompetent male patient. The patient was admitted to our
      hospital after suffering for nine days from epigastralgia and obstructive
      jaundice. Computed tomography revealed a pancreatic mass that mimicked a
      pancreatic head carcinoma. The patient had undergone an operation four months
      prior for thoracic TB and was undergoing anti-TB therapy. A previous abdominal
      ultrasound was unremarkable with the exception of gallbladder steroid deposits.
      The patient underwent surgery due to the progressive discomfort of the upper
      abdomen and a mass that resembled a pancreatic malignancy. A biopsy of the
      pancreas and lymph nodes was performed, revealing TB infection. The patient
      received a cholecystostomy tube and recovered after being administered standard
      anti-TB therapy for 15 mo. This case is reported to emphasize the rare
      contribution of pancreatic TB to pancreatic masses and obstructive jaundice. 

PMID- 24868518
TI  - Vasculitis with renal involvement in essential mixed cryoglobulinemia: Case
      report and mini-review.
AB  - The discovery of a strong association between hepatitis C virus (HCV) infection
      and mixed cryoglobulinemia (MC) has led to an increasingly rare diagnosis of
      idiopathic essential MC (EMC). The incidence of EMC is high in regions where
      there is a comparatively low HCV infection burden and low in areas of high
      infection prevalence, including HCV. The diagnosis of EMC requires an extensive
      laboratory investigation to exclude all possible causes of cryoglobulin
      formation. In addition, although cryoglobulin testing is simple, improper testing
      conditions will result in false negative results. Here, we present a 46-year-old
      female patient with a case of EMC with dermatological and renal manifestations,
      highlighting the importance of extensive investigation to reach a proper
      diagnosis. We review the need for appropriate laboratory testing, which is often
      neglected in clinical practice and which can result in false negative results.
      This review also emphasizes the significance of an extended testing repertoire
      necessary for better patient management. Despite a strong association of MC with
      HCV infection and other causes that lead to cryoglobulin formation, EMC remains a
      separate entity. Correct diagnosis requires proper temperature regulation during
      sample handling, as well as characterization and quantification of the
      cryoprecipitate. Inclusion of rheumatoid factor activity and complement levels in
      the cryoglobulin test-panel promotes better patient management and monitoring.
      Consensus guidelines should be developed and implemented for cryoglobulin
      detection and the diagnosis of cryoglobulinemic syndrome, which will reduce
      variability in inter-laboratory reporting. 

PMID- 24868520
TI  - Pneumomediastinum after acute lymphoblastic leukemia and chemotherapy?
AB  - Pneumomediastinum, pneumorachis and subcutaneous emphysema are frequently benign
      and most commonly result from air escaping from the upper respiratory tract,
      intrathoracic airways, or gastrointestinal tract. Gas can also be generated by
      certain infections or reach the mediastinal space from outside air after trauma
      or surgery. In the article presented by Showkat et al a 14-year-old male patient
      with acute lymphoblastic leukemia (ALL) under chemotherapy developed
      pneumomediastinum, pneumorachis and subcutaneous emphysema. In the author's
      opinion, these complications were caused by ALL or chemotherapy that progressed
      to severe respiratory failure until the patient finally died in the intensive
      care unit. I would like to underline some important points, which have been
      raised following a paper published in the October issue of World Journal of
      Clinical Cases. 

PMID- 24868522
TI  - Retracted: Downregulation of ADAM10 expression inhibits metastasis and
      invasiveness of human hepatocellular carcinoma HepG2 cells.

PMID- 24868521
TI  - Hyperammonemia associated with valproic acid concentrations.
AB  - Valproic acid, a branched short-chain fatty acid, has numerous action mechanisms
      which turn it into a broad spectrum anticonvulsant drug and make its use possible
      in some other pathologies such as bipolar disorder. It is extensively metabolized
      in liver, representing beta -oxidation in the mitochondria one of its main
      metabolic route (40%). Carnitine is responsible for its entry into the
      mitochondria as any other fatty acid. Long-term high-dose VPA therapy or acute
      VPA overdose induces carnitine depletion, resulting in high levels of ammonia in
      blood. As a high correlation between salivary valproic acid levels and plasma
      ultrafiltrate levels was found in humans, saliva becomes a promising monitoring
      fluid in order to study valproic acid pharmacokinetics and its toxic effect.
      Extended-release (twice daily) formulations of valproic acid or carnitine
      supplementation are the proposed two therapeutic strategies in order to reverse
      hyperammonemia. 

PMID- 24868523
TI  - The osteogenesis of bone marrow stem cells on mPEG-PCL-mPEG/hydroxyapatite
      composite scaffold via solid freeform fabrication.
AB  - The study described a novel bone tissue scaffold fabricated by computer-aided,
      air pressure-aided deposition system to control the macro- and microstructure
      precisely. The porcine bone marrow stem cells (PBMSCs) seeded on either mPEG-PCL
      mPEG (PCL) or mPEG-PCL-mPEG/hydroxyapatite (PCL/HA) composite scaffold were
      cultured under osteogenic medium to test the ability of osteogenesis in vitro.
      The experimental outcomes indicated that both scaffolds possessed adequate pore
      size, porosity, and hydrophilicity for the attachment and proliferation of PBMSCs
      and the PBMSCs expressed upregulated genes of osteogensis and angiogenesis in
      similar manner on both scaffolds. The major differences between these two types
      of the scaffolds were the addition of HA leading to higher hardness of PCL/HA
      scaffold, cell proliferation, and VEGF gene expression in PCL/HA scaffold.
      However, the in vivo bone forming efficacy between PBMSCs seeded PCL and PCL/HA
      scaffold was different from the in vitro results. The outcome indicated that the
      PCL/HA scaffold which had bone-mimetic environment due to the addition of HA
      resulted in better bone regeneration and mechanical strength than those of PCL
      scaffold. Therefore, providing a bone-mimetic scaffold is another crucial factor
      for bone tissue engineering in addition to the biocompatibility, 3D architecture
      with high porosity, and interpored connection. 

PMID- 24868524
TI  - Vastus medialis obliquus muscle morphology in primary and recurrent lateral
      patellar instability.
AB  - The morphology of the vastus medialis obliquus (VMO) muscle in the anatomical
      setting of an unstable patella has not been described. Therefore, the purpose of
      this study was to investigate the morphological parameters of the VMO muscle that
      delineate its importance in the maintenance of patellofemoral joint stability.
      Eighty-two consecutive subjects were prospectively enrolled in this study. The
      groups were composed of thirty patients with an acute primary patellar
      dislocation, thirty patients with recurrent patellar dislocation, and twenty-two
      controls. Groups were adjusted according to sex, age, body mass index, and
      physical activity. Magnetic resonance imaging was used to measure the VMO cross
      sectional area, muscle-fiber angulation, and the craniocaudal extent of the
      muscle in relation to the patella. No significant difference was found with
      respect to all measured VMO parameters between primary dislocation, recurrent
      dislocation, and control subjects with a trend noted for only the VMO cross
      sectional area and the VMO muscle-fiber angulation. This finding is notable in
      that atrophy of the VMO has often been suggested to play an important role in the
      pathophysiology of an unstable patellofemoral joint. 

PMID- 24868525
TI  - New insights into c-Ret signalling pathway in the enteric nervous system and its
      relationship with ALS.
AB  - The receptor tyrosine kinase Ret (c-Ret) transduces the glial cell line-derived
      neurotrophic factor (GDNF) signal, one of the neurotrophic factors related to the
      degeneration process or the regeneration activity of motor neurons in amyotrophic
      lateral sclerosis (ALS). The phosphorylation of several tyrosine residues of c
      Ret seems to be altered in ALS. c-Ret is expressed in motor neurons and in the
      enteric nervous system (ENS) during the embryonic period. The characteristics of
      the ENS allow using it as model for central nervous system (CNS) study and being
      potentially useful for the research of human neurological diseases such as ALS.
      The aim of the present study was to investigate the cellular localization and
      quantitative evaluation of marker c-Ret in the adult human gut. To assess the
      nature of c-Ret positive cells, we performed colocalization with specific markers
      of cells that typically are located in the enteric ganglia. The colocalization of
      PGP9.5 and c-Ret was preferentially intense in enteric neurons with oval
      morphology and mostly peripherally localized in the ganglion, so we concluded
      that the c-Ret receptor is expressed by a specific subtype of enteric neurons in
      the mature human ENS of the gut. The functional significance of these c-Ret
      positive neurons is discussed. 

PMID- 24868526
TI  - Stereotactic ablative radiotherapy for oligometastatic disease in liver.
AB  - Liver metastasis in solid tumors, including colorectal cancer, is the most
      frequent and lethal complication. The development of systemic therapy has led to
      prolonged survival. However, in selected patients with a finite number of
      discrete lesions in liver, defined as oligometastatic state, additional local
      therapies such as surgical resection, radiofrequency ablation, cryotherapy, and
      radiotherapy can lead to permanent local disease control and improve survival.
      Among these, an advance in radiation therapy made it possible to deliver high
      dose radiation to the tumor more accurately, without impairing the liver
      function. In recent years, the introduction of stereotactic ablative radiotherapy
      (SABR) has offered even more intensive tumor dose escalation in a few fractions
      with reduced dose to the adjacent normal liver. Many studies have shown that SABR
      for oligometastases is effective and safe, with local control rates widely
      ranging from 50% to 100% at one or two years. And actuarial survival at one and
      two years has been reported ranging from 72% to 94% and from 30% to 62%,
      respectively, without severe toxicities. In this paper, we described the
      definition and technical aspects of SABR, clinical outcomes including efficacy
      and toxicity, and related parameters after SABR in liver oligometastases from
      colorectal cancer. 

PMID- 24868527
TI  - Evaluation of three automated nucleic acid extraction systems for identification
      of respiratory viruses in clinical specimens by multiplex real-time PCR.
AB  - A total of 84 nasopharyngeal swab specimens were collected from 84 patients.
      Viral nucleic acid was extracted by three automated extraction systems: QIAcube
      (Qiagen, Germany), EZ1 Advanced XL (Qiagen), and MICROLAB Nimbus IVD (Hamilton,
      USA). Fourteen RNA viruses and two DNA viruses were detected using the Anyplex II
      RV16 Detection kit (Seegene, Republic of Korea). The EZ1 Advanced XL system
      demonstrated the best analytical sensitivity for all the three viral strains. The
      nucleic acids extracted by EZ1 Advanced XL showed higher positive rates for virus
      detection than the others. Meanwhile, the MICROLAB Nimbus IVD system was
      comprised of fully automated steps from nucleic extraction to PCR setup function
      that could reduce human errors. For the nucleic acids recovered from
      nasopharyngeal swab specimens, the QIAcube system showed the fewest false
      negative results and the best concordance rate, and it may be more suitable for
      detecting various viruses including RNA and DNA virus strains. Each system showed
      different sensitivity and specificity for detection of certain viral pathogens
      and demonstrated different characteristics such as turnaround time and sample
      capacity. Therefore, these factors should be considered when new nucleic acid
      extraction systems are introduced to the laboratory. 

PMID- 24868528
TI  - Experience of preimplantation genetic diagnosis with HLA matching at the
      University Hospital Virgen del Rocio in Spain: technical and clinical overview.
AB  - Preimplantation genetic diagnosis (PGD) of genetic diseases, combined with HLA
      matching (PGD-HLA), is an option for couples at risk of transmitting a genetic
      disease to select unaffected embryos of an HLA tissue type compatible with that
      of an existing affected child. Here we present the results of our PGD-HLA program
      at the Department of Genetics, Reproduction and Fetal Medicine of the University
      Hospital Virgen del Rocio in Seville. Seven couples have participated in our
      program because of different indications. Overall, 26 cycles were performed,
      providing a total of 202 embryos. A conclusive molecular diagnosis and HLA-typing
      could be assured in 96% of the embryos. The percentage of transfers per cycle was
      26.9% and the birth rate per cycle was 7.7% per transfer. Our PGD-HLA program
      resulted in the birth of 2 healthy babies, HLA-identical to their affected
      siblings, with successful subsequent haematopoietic stem cell (HSC)
      transplantations. Both HSC-transplanted children are currently doing well 48 and
      21 months following transplantation, respectively. All the procedures, including
      HSCs umbilical cord transplantation, were performed in our hospital. 

PMID- 24868530
TI  - The significance of serum phosphate level on healing index and its relative
      effects in skeletally immature and mature patients with hypophosphatemic rickets.
AB  - The aim of this study was to find out the ideal cut-off level of phosphate for
      safe healing when deformity correction and concomitant lengthening are indicated
      in the two different skeletal maturity groups of patients with rickets. Thirty
      nine hypophosphatemic rickets patients were selected for the study and were
      divided into two groups: 27 skeletally immature (group IM) and 12 skeletally
      mature (group M). The outcomes were evaluated with respect to the healing index
      (HI), laboratory findings, and complications with the mean follow-up of 5.1 years
      (range, 3.1-7.9). The healing index (HI) of group IM was 1.44 month/cm and HI of
      group M was 1.68 month/cm. The negative correlation between the level of serum
      phosphate and HI in group M (coefficient=-0.94) was evaluated to be less than the
      correlation in group IM (coefficient=-0.50), indicating that the HI is more
      likely to be affected by serum phosphate in group M than in group IM.
      Preoperative serum phosphate levels of 2.3 mg/dL and 2.6 mg/dL were analyzed to
      be the cut-off values of group IM and group M, respectively, in which the cut-off
      points divided the series into two groups having the most significantly different
      HI.

PMID- 24868532
TI  - Fenugreek seed extract inhibit fat accumulation and ameliorates dyslipidemia in
      high fat diet-induced obese rats.
AB  - This study investigated the inhibitory effect of aqueous extract of Trigonella
      foenum-graecum seeds (AqE-TFG) on fat accumulation and dyslipidemia in high fat
      diet- (HFD-) induced obese rats. Female Wistar rats were fed with HFD ad libitum,
      and the rats on HFD were treated orally with AqE-TFG or orlistat ((HFD for 28
      days+AqE-TFG (0.5 and 1.0 g/kg) or orlistat (10 mg/kg) from day 8 to 28),
      respectively. Treatment with AqE-TFG produced significant reduction in body
      weight gain, body mass index (BMI), white adipose tissue (WAT) weights, blood
      glucose, serum insulin, lipids, leptin, lipase, and apolipoprotein-B levels and
      elevation in adiponectin levels. AqE-TFG improved serum aspartate amino
      transferase (AST), alanine amino transferase (ALT), and lactate dehydrogenase
      (LDH) levels. AqE-TFG treatment reduced the hepatic and cardiac thiobarbituric
      acid reactive substances (TBARS) and elevated the antioxidant enzyme (glutathione
      (GSH), superoxide dismutase (SOD), and catalase (CAT)) levels. In addition, liver
      and uterine WAT lipogenic enzyme (fatty acid synthetase (FAS) and glucose-6
      phosphate dehydrogenase (G6PD)) activities were restored towards normal levels.
      These findings demonstrated the preventive effect of AqE-TFG on fat accumulation
      and dyslipidemia, due to inhibition of impaired lipid digestion and absorption,
      in addition to improvement in glucose and lipid metabolism, enhancement of
      insulin sensitivity, increased antioxidant defense, and downregulation of
      lipogenic enzymes.

PMID- 24868531
TI  - Oral and intraperitoneal administration of quercetin decreased lymphocyte DNA
      damage and plasma lipid peroxidation induced by TSA in vivo.
AB  - Our previous study showed that quercetin enhances the anticancer effect of
      trichostatin A (TSA) in xenograft mice given quercetin intraperitoneally (10
      mg/kg, 3 times/week). Herein, we investigate whether quercetin administered
      orally exerts such an effect and prevents the cytotoxic side effects of TSA. We
      found that quercetin given orally (20 and 100 mg/kg, 3 times/week) failed to
      enhance the antitumor effect of TSA although it increased the total quercetin
      concentration more than quercetin administered intraperitoneally in the plasma.
      The compound quercetin-3-glucuronide (Q3G) increased the most. However, quercetin
      administered intraperitoneally increased the total quercetin level in tumor
      tissues more than oral quercetin. Oral and intraperitoneal administration of
      quercetin similarly decreased lymphocyte DNA damage and plasma lipid peroxidation
      level induced by TSA. Furthermore, we found that the enhancing effect of Q3G on
      the antitumor effect of TSA and the incorporation of Q3G was less than that of
      quercetin in A549 cells. However, we found that A549 cells possessed the ability
      to convert Q3G to quercetin. In conclusion, different from quercetin administered
      intraperitoneally, quercetin administered orally failed to enhance the antitumor
      effect of TSA because of its metabolic conversion. However, it prevented TSA
      induced DNA damage and lipid peroxidation. 

PMID- 24868533
TI  - Prevalence of HIV and syphilis infection among men who have sex with men in
      China: a meta-analysis.
AB  - OBJECTIVES: To figure out the most current prevalence of HIV and syphilis in MSM
      in China. METHODS: A meta-analysis was conducted on the studies searched through
      PubMed, CNKI, and Wanfang published between 1 January 2009 and 11 April 2013.
      RESULTS: Eighty-four eligible studies, either in Chinese or in English, were
      included in this review. The pooled prevalence of HIV and syphilis infection in
      MSM in China was 6.5% and 11.2%, respectively. The subgroup analyses indicated
      that the prevalence of HIV infection was higher in the economically less
      developed cities than that in the developed cities (7.5% versus 6.1%, P<0.05). In
      contrast, the prevalence of syphilis infection was lower in less developed cities
      than in developed cities (8.6% versus 15.1%). Studies with a sample size smaller
      than 500 had a lower prevalence of HIV and syphilis infection than those with a
      sample size greater than 500 (5.9% versus 7.2% for HIV; 11.0% versus 11.5% for
      syphilis, respectively). CONCLUSIONS: HIV and syphilis infection are prevalent in
      MSM in China. The different prevalence of HIV and syphilis infection between
      developing and developed cities underscores the need to target prevention
      strategies based on economic conditions.

PMID- 24868534
TI  - Taking bacteriophage therapy seriously: a moral argument.
AB  - The excessive and improper use of antibiotics has led to an increasing incidence
      of bacterial resistance. In Europe the yearly number of infections caused by
      multidrug resistant bacteria is more than 400.000, each year resulting in 25.000
      attributable deaths. Few new antibiotics are in the pipeline of the
      pharmaceutical industry. Early in the 20th century, bacteriophages were described
      as entities that can control bacterial populations. Although bacteriophage
      therapy was developed and practiced in Europe and the former Soviet republics,
      the use of bacteriophages in clinical setting was neglected in Western Europe
      since the introduction of traditional antibiotics. Given the worldwide antibiotic
      crisis there is now a growing interest in making bacteriophage therapy available
      for use in modern western medicine. Despite the growing interest, access to
      bacteriophage therapy remains highly problematic. In this paper, we argue that
      the current state of affairs is morally unacceptable and that all stakeholders
      (pharmaceutical industry, competent authorities, lawmakers, regulators, and
      politicians) have the moral duty and the shared responsibility towards making
      bacteriophage therapy urgently available for all patients in need. 

PMID- 24868529
TI  - The three genetics (nuclear DNA, mitochondrial DNA, and gut microbiome) of
      longevity in humans considered as metaorganisms.
AB  - Usually the genetics of human longevity is restricted to the nuclear genome
      (nDNA). However it is well known that the nDNA interacts with a physically and
      functionally separated genome, the mitochondrial DNA (mtDNA) that, even if
      limited in length and number of genes encoded, plays a major role in the ageing
      process. The complex interplay between nDNA/mtDNA and the environment is most
      likely involved in phenomena such as ageing and longevity. To this scenario we
      have to add another level of complexity represented by the microbiota, that is,
      the whole set of bacteria present in the different part of our body with their
      whole set of genes. In particular, several studies investigated the role of gut
      microbiota (GM) modifications in ageing and longevity and an age-related GM
      signature was found. In this view, human being must be considered as
      "metaorganism" and a more holistic approach is necessary to grasp the complex
      dynamics of the interaction between the environment and nDNA-mtDNA-GM of the host
      during ageing. In this review, the relationship between the three genetics and
      human longevity is addressed to point out that a comprehensive view will allow
      the researchers to properly address the complex interactions that occur during
      human lifespan. 

PMID- 24868535
TI  - Low perceived social support is associated with CD8+CD57+ lymphocyte expansion
      and increased TNF-alpha levels.
AB  - Social support has been supposed to have a positive impact on the function of the
      immune system. However, the relationship between perceived social support and
      immune function has not yet been fully investigated. In this cross-sectional
      study, we investigated the link between perceived social support and lymphocyte
      subpopulations and cytokines. 232 healthy subjects provided a blood sample and
      completed the Multidimensional Scale of Perceived Social Support (MSPSS)
      questionnaire. Lymphocyte immunophenotypes and cytokines were determined.
      Significantly increased CD8+CD57+ lymphocytes and TNF-alpha levels were found in
      group with low perceived social support. Multivariate linear regression corrected
      for possible confounders confirmed a significant role of perceived social support
      in predicting the number of CD8+CD57+ lymphocyte and TNF-alpha levels. This study
      supports the association between perceived social support and immune function. In
      particular, poor social support may be related to a state of chronic inflammation
      sustained by CD8+CD57+ lymphocyte expansion and increased TNF-alpha levels.

PMID- 24868536
TI  - Kinematic analysis of the upper limb motor strategies in stroke patients as a
      tool towards advanced neurorehabilitation strategies: a preliminary study.
AB  - Advanced rehabilitation strategies of the upper limb in stroke patients focus on
      the recovery of the most important daily activities. In this study we analyzed
      quantitatively and qualitatively the motor strategies employed by stroke patients
      when reaching and drinking from a glass. We enrolled 6 hemiparetic poststroke
      patients and 6 healthy subjects. Motion analysis of the task proposed (reaching
      for the glass, bringing it to the mouth, and putting it back on the table) with
      the affected limb was performed. Clinical assessment using the Fugl-Meyer
      Assessment for Upper Extremity was also included. During the reaching for the
      glass the patients showed a reduced arm elongation and trunk axial rotation due
      to motor deficit. For this reason, as observed, they carried out compensatory
      strategies which included trunk forward displacement and head movements. These
      preliminary data should be considered to address rehabilitation treatment.
      Moreover, the kinematic analysis protocol developed might represent an outcome
      measure of upper limb rehabilitation processes. 

PMID- 24868537
TI  - Reliability in the parameterization of the functional reach test in elderly
      stroke patients: a pilot study.
AB  - BACKGROUND: Postural instability is one of the major complications found in
      stroke survivors. Parameterising the functional reach test (FRT) could be useful
      in clinical practice and basic research. OBJECTIVES: To analyse the reliability,
      sensitivity, and specificity in the FRT parameterisation using inertial sensors
      for recording kinematic variables in patients who have suffered a stroke. DESIGN:
      Cross-sectional study. While performing FRT, two inertial sensors were placed on
      the patient's back (lumbar and trunk). PARTICIPANTS: Five subjects over 65 who
      suffer from a stroke. MEASUREMENTS: FRT measures, lumbosacral/thoracic maximum
      angular displacement, maximum time of lumbosacral/thoracic angular displacement,
      time return initial position, and total time. Speed and acceleration of the
      movements were calculated indirectly. RESULTS: FRT measure is  12.75+/-2.06 cm.
      Intrasubject reliability values range from 0.829 (time to return initial position
      (lumbar sensor)) to 0.891 (lumbosacral maximum angular displacement).
      Intersubject reliability values range from 0.821 (time to return initial position
      (lumbar sensor)) to 0.883 (lumbosacral maximum angular displacement). FRT's
      reliability was 0.987 (0.983-0.992) and 0.983 (0.979-0.989) intersubject and
      intrasubject, respectively. CONCLUSION: The main conclusion could be that the
      inertial sensors are a tool with excellent reliability and validity in the
      parameterization of the FRT in people who have had a stroke.

PMID- 24868538
TI  - Analysis of the associations between vitamin D and albuminuria or beta-cell
      function in Chinese type 2 diabetes.
AB  - OBJECTIVE: To investigate the associations of 25-(OH)D and beta -cell function or
      insulin resistance or albuminuria in Chinese type 2 diabetic patients. METHODS:
      In total, 1408 type 2 diabetic patients without vitamin D supplement were
      included in this retrospective study. RESULTS: Comparison between patients with
      and without 25-(OH)D deficiency indicated that, compared with patients with 25
      (OH)D>=50 nmol/L, patients with 25-(OH)D<50 nmol/L showed a higher level of urine
      albumin-creatinine ratio (ACR) (90.15+/-10.30 mg/g versus 52.79+/-14.97 mg/g).
      Multiple regression analysis indicated that 25-(OH)D was independently and
      negatively correlated with urine ACR (OR=0.985, 95%CI 0.972-0.999, P=0.03),
      adjusted by age, diabetic duration, HBP duration, SBP, HbA1c, creatinine, LDL-C,
      triglyceride, total cholesterol, and HDL-C. Compared with patients with normal
      level of urine ACR, patients with higher level of urine ACR showed a significant
      lower level of 25-(OH)D (34.49+/-13.52 nmol/L versus 37.46+/-13.6 nmol/L,
      P=0.00). Analysis of the associations of 25-(OH)D and beta-cell function or
      insulin resistance showed that 25-(OH)D may not correlate with beta-cell function
      or insulin resistance. CONCLUSION: 25-(OH)D was independently associated with
      albuminuria in Chinese type 2 diabetic patients but was not associated with beta
      cell function or insulin resistance.

PMID- 24868539
TI  - Computational prediction of protein function based on weighted mapping of domains
      and GO terms.
AB  - In this paper, we propose a novel method, SeekFun, to predict protein function
      based on weighted mapping of domains and GO terms. Firstly, a weighted mapping of
      domains and GO terms is constructed according to GO annotations and domain
      composition of the proteins. The association strength between domain and GO term
      is weighted by symmetrical conditional probability. Secondly, the mapping is
      extended along the true paths of the terms based on GO hierarchy. Finally, the
      terms associated with resident domains are transferred to host protein and real
      annotations of the host protein are determined by association strengths. Our
      careful comparisons demonstrate that SeekFun outperforms the concerned methods on
      most occasions. SeekFun provides a flexible and effective way for protein
      function prediction. It benefits from the well-constructed mapping of domains and
      GO terms, as well as the reasonable strategy for inferring annotations of protein
      from those of its domains. 

PMID- 24868540
TI  - IDH1/IDH2 but not TP53 mutations predict prognosis in Bulgarian glioblastoma
      patients.
AB  - Mutations in genes encoding isocitrate dehydrogenase isoforms 1 (IDH1) and 2
      (IDH2) have been associated with good prognosis for patients with brain
      neoplasias and have been commonly found together with mutated TP53 gene. To
      determine the prevalence of IDH1, IDH2, and TP53 mutations and their impact on
      overall survival 106 glioblastoma patients were analysed. IDH1 mutations were
      detected in 13 and IDH2 mutation in one patient. Two homozygous samples with
      R132H mutation in IDH1 gene and a novel aberration K129R in IDH2 gene were found.
      Sixty-four percent of IDH1/IDH2 mutated tumours harboured also a mutation in TP53
      gene. Genetic aberrations in TP53 were present in 37 patients. Statistical
      analysis of the impact of the studied factors on the overall survival showed that
      the mutations in IDH1/IDH2, but not the ones in TP53, were associated with longer
      survival. Also, the impact of age on prognosis was confirmed. This is the first
      comprehensive study on glioblastomas in Bulgaria. Our results suggest that
      IDH1/IDH2 but not TP53 mutations together with other prognostic factors such as
      age might be applied in clinical practice for prediction of outcome in patients
      with glioblastomas. 

PMID- 24868541
TI  - Emergent bacteria in cystic fibrosis: in vitro biofilm formation and resilience
      under variable oxygen conditions.
AB  - Concurrent to conventional bacterial pathogens, unusual microbes are emerging
      from cystic fibrosis (CF) airways. Nonetheless, little is known about the
      contribution of these newly microbes to the resilience of CF-associated biofilms,
      particularly under variable-oxygen concentrations that are known to occur in vivo
      in the mucus of CF patients. Two CF-emergent bacterial species, Inquilinus
      limosus and Dolosigranulum pigrum, and the major pathogen Pseudomonas aeruginosa
      were studied in terms of biofilm development and antibiotic susceptibilities
      under in vitro atmospheres with different oxygen availabilities. All species were
      able to develop in vitro biofilms under different oxygen-available environments,
      with D. pigrum accumulating high amounts of biomass and respiratory activities.
      When established, biofilms were of difficult eradication, with antibiotics losing
      their effectiveness in comparison with the corresponding planktonic populations.
      Surprisingly, biofilms of each emergent organism displayed multidrug resistance
      under aerobic environments, enduring even in low-oxygen atmospheres. This study
      suggests a potential prospect on the impact of nonconventional organisms I.
      limosus and D. pigrum on CF lung infections, demonstrating capacity to adapt to
      biofilm mode of life under restricted-oxygen atmospheres resembling CF airways,
      which may ultimately endanger the efficacy of currently used antibiotic regimens.

PMID- 24868542
TI  - Nuclear distribution of RNA polymerase II and mRNA processing machinery in early
      mammalian embryos.
AB  - Spatial distribution of components of nuclear metabolism provides a significant
      impact on regulation of the processes of gene expression. While distribution of
      the key nuclear antigens and their association with the defined nuclear domains
      were thoroughly traced in mammalian somatic cells, similar data for the
      preimplantation embryos are scanty and fragmental. However, the period of
      cleavage is characterized by the most drastic and dynamic nuclear reorganizations
      accompanying zygotic gene activation. In this minireview, we try to summarize the
      results of studies concerning distribution of major factors involved in RNA
      polymerase II-dependent transcription, pre-mRNA splicing mRNA export that have
      been carried out on early embryos of mammals. 

PMID- 24868543
TI  - Amelioration of paracetamol-induced hepatotoxicity in rat by the administration
      of methanol extract of Muntingia calabura L. leaves.
AB  - Muntingia calabura L. is a tropical plant species that belongs to the
      Elaeocarpaceae family. The present study is aimed at determining the
      hepatoprotective activity of methanol extract of M. calabura leaves (MEMC) using
      two models of liver injury in rats. Rats were divided into five groups (n=6) and
      received 10% DMSO (negative control), 50 mg/kg N-acetylcysteine (NAC; positive
      control), or MEMC (50, 250, and 500 mg/kg) orally once daily for 7 days and on
      the 8th day were subjected to the hepatotoxic induction using paracetamol (PCM).
      The blood and liver tissues were collected and subjected to biochemical and
      microscopical analysis. The extract was also subjected to antioxidant study using
      the 2,2-diphenyl-1-picrylhydrazyl-(DPPH) and superoxide anion-radical scavenging
      assays. At the same time, oxygen radical antioxidant capacity (ORAC) and total
      phenolic content were also determined. From the histological observation,
      lymphocyte infiltration and marked necrosis were observed in PCM-treated groups
      (negative control), whereas maintenance of hepatic structure was observed in
      group pretreated with N-acetylcysteine and MEMC. Hepatotoxic rats pretreated with
      NAC or MEMC exhibited significant decrease (P<0.05) in ALT and AST enzymes level.
      Moreover, the extract also exhibited good antioxidant activity. In conclusion,
      MEMC exerts potential hepatoprotective activity that could be partly attributed
      to its antioxidant activity and, thus warrants further investigations.

PMID- 24868545
TI  - Amarogentin, a secoiridoid glycoside, abrogates platelet activation through PLC
      gamma 2-PKC and MAPK pathways.
AB  - Amarogentin, an active principle of Gentiana lutea, possess antitumorigenic,
      antidiabetic, and antioxidative properties. Activation of platelets is associated
      with intravascular thrombosis and cardiovascular diseases. The present study
      examined the effects of amarogentin on platelet activation. Amarogentin treatment
      (15~60  MUM) inhibited platelet aggregation induced by collagen, but not
      thrombin, arachidonic acid, and U46619. Amarogentin inhibited collagen-induced
      phosphorylation of phospholipase C (PLC) gamma2, protein kinase C (PKC), and
      mitogen-activated protein kinases (MAPKs). It also inhibits in vivo thrombus
      formation in mice. In addition, neither the guanylate cyclase inhibitor ODQ nor
      the adenylate cyclase inhibitor SQ22536 affected the amarogentin-mediated
      inhibition of platelet aggregation, which suggests that amarogentin does not
      regulate the levels of cyclic AMP and cyclic GMP. In conclusion, amarogentin
      prevents platelet activation through the inhibition of PLC gamma2-PKC cascade and
      MAPK pathway. Our findings suggest that amarogentin may offer therapeutic
      potential for preventing or treating thromboembolic disorders.

PMID- 24868544
TI  - Guidelines on vaccinations in paediatric haematology and oncology patients.
AB  - OBJECTIVE: Vaccinations are the most important tool to prevent infectious
      diseases. Chemotherapy-induced immune depression may impact the efficacy of
      vaccinations in children. PATIENTS AND METHODS: A panel of experts of the
      supportive care working group of the Italian Association Paediatric Haematology
      Oncology (AIEOP) addressed this issue by guidelines on vaccinations in paediatric
      cancer patients. The literature published between 1980 and 2013 was reviewed.
      RESULTS AND CONCLUSION: During intensive chemotherapy, vaccination turned out to
      be effective for hepatitis A and B, whilst vaccinations with toxoid, protein
      subunits, or bacterial antigens should be postponed to the less intensive phases,
      to achieve an adequate immune response. Apart from varicella, the administration
      of live-attenuated-virus vaccines is not recommended during this phase. Family
      members should remain on recommended vaccination schedules, including toxoid,
      inactivated vaccine (also poliomyelitis), and live-attenuated vaccines
      (varicella, measles, mumps, and rubella). By the time of completion of
      chemotherapy, insufficient serum antibody levels for vaccine-preventable diseases
      have been reported, while immunological memory appears to be preserved. Once
      immunological recovery is completed, usually after 6 months, response to booster
      or vaccination is generally good and allows patients to be protected and also to
      contribute to herd immunity.

PMID- 24868546
TI  - Efficacy of physiotherapy for urinary incontinence following prostate cancer
      surgery.
AB  - The study enrolled 81 with urinary incontinence following radical prostate-only
      prostatectomy for prostatic carcinoma. The patients were divided into two groups.
      The patients in Group I were additionally subdivided into two subgroups with
      respect to the physiotherapeutic method used. The patients of subgroup IA
      received a rehabilitation program consisting of three parts. The patients of
      subgroup IB rehabilitation program consist of two parts. Group II, a control
      group, had reported for therapy for persistent urinary incontinence following
      radical prostatectomy but had not entered therapy for personal reasons. For
      estimating the level of incontinence, a 1-hour and 24-hour urinary pad tests, the
      miction diary, and incontinence questionnaire were used, and for recording the
      measurements of pelvic floor muscles tension, the sEMG (surface electromyography)
      was applied. The therapy duration depended on the level of incontinence and it
      continued for not longer than 12 months. Superior continence outcomes were
      obtained in Group I versus Group II and the difference was statistically
      significant. The odds ratio for regaining continence was greater in the
      rehabilitated Group I and smaller in the group II without the rehabilitation. A
      comparison of continence outcomes revealed a statistically significant difference
      between Subgroups IA versus IB. The physiotherapeutic procedures applied on
      patients with urine incontinence after prostatectomy, for most of them, proved to
      be an effective way of acting, which is supported by the obtained results. 

PMID- 24868547
TI  - Correlation between urothelial differentiation and sensory proteins P2X3, P2X5,
      TRPV1, and TRPV4 in normal urothelium and papillary carcinoma of human bladder.
AB  - Terminal differentiation of urothelium is a prerequisite for blood-urine barrier
      formation and enables normal sensory function of the urinary bladder. In this
      study, urothelial differentiation of normal human urothelium and of low and high
      grade papillary urothelial carcinomas was correlated with the expression and
      localization of purinergic receptors (P2X3, and P2X5) and transient receptor
      potential vanilloid channels (TRPV1, and TRPV4). Western blotting and
      immunofluorescence of uroplakins together with scanning electron microscopy of
      urothelial apical surface demonstrated terminal differentiation of normal
      urothelium, partial differentiation of low grade carcinoma, and poor
      differentiation of high grade carcinoma. P2X3 was expressed in normal urothelium
      as well as in low grade carcinoma and in both cases immunolabeling was stronger
      in the superficial cells. P2X3 expression decreased in high grade carcinoma. P2X5
      expression was detected in normal urothelium and in high grade carcinoma, while
      in low grade carcinoma its expression was diminished. The expression of TRPV1
      decreased in low grade and even more in high grade carcinoma when compared with
      normal urothelium, while TRPV4 expression was unchanged in all samples. Our
      results suggest that sensory proteins P2X3 and TRPV1 are in correlation with
      urothelial differentiation, while P2X5 and TRPV4 have unique expression patterns.

PMID- 24868548
TI  - Repeatability of ocular measurements with a dual-Scheimpflug analyzer in healthy
      eyes.
AB  - PURPOSE: To assess the repeatability of the Galilei dual Scheimpflug analyzer
      (GDSA) in anterior segment examination. METHODS: Fifty-two eyes from 52 healthy
      volunteers were prospectively and consecutively recruited. Anatomic, axial,
      refractive, and instantaneous parameters were measured with GDSA to provide a
      complete characterization of the anterior segment. Repeatability was assessed
      calculating intraclass correlation coefficient (ICC), and coefficient of
      variation (COV). RESULTS: Correlation among repeated measurements showed almost
      perfect reliability (ICC>0.81) for all parameters except thinnest central corneal
      thickness (CCT) (0.78), corneal thickness average out (0.79), and posterior axial
      curvature average out (0.60). Repeatability was excellent (COV<10%) for all
      parameters except anterior chamber volume and, superior iridocorneal angle and
      eccentricities. In these last three parameters, repeatability limits were
      excessively high compared to the mean. CONCLUSIONS: GDSA in healthy young persons
      had an almost perfect correlation in measuring anatomic, axial, instantaneous,
      and refractive parameters with greater variability for peripheral terms.
      Repeatability of anatomical parameters like pachymetry, anterior chamber, or
      iridocorneal angle and eccentricity were limited. In healthy young persons, the
      other evaluated parameters had very good repeatability and their limits of
      agreement showed excellent clinical results for this device.

PMID- 24868549
TI  - Different bleeding patterns with the use of levonorgestrel intrauterine system:
      are they associated with changes in uterine artery blood flow?
AB  - OBJECTIVE: Evaluate if different bleeding patterns associated with the use of the
      levonorgestrel intrauterine system (LNG-IUS) are associated with different
      uterine and endometrial vascularization patterns, as evidenced by ultrasound
      power Doppler analysis. METHODOLOGY: A longitudinal study, with each subject
      acting as its own control was conducted between January 2010 and December 2012.
      Healthy volunteers with a history of heavy but cyclic and regular menstrual
      cycles were enrolled in the study. Ultrasonographic examination was performed
      before and after six months of LNG-IUS placement: uterine volume, endometrial
      thickness, and subendometrial and myometrial Doppler blood flow patterns have
      been evaluated. RESULTS: A total of 32 women were enrolled out of 186 initially
      screened. At six months of follow-up, all subjects showed a reduction in
      menstrual blood loss; for analysis, they were retrospectively divided into 3
      groups: normal cycling women (Group I), amenorrheic women (Group II), and women
      with prolonged bleedings (Group III). Intergroup analysis documented a
      statistically significant difference in endometrial thickness among the three
      groups; in addition, mean pulsatility index (PI) and resistance index (RI) in the
      spiral arteries were significantly lower in Group I and Group III compared to
      Group II. This difference persisted also when comparing--within subjects of Group
      III--mean PI and RI mean values before and after insertion. CONCLUSIONS: The LNG
      IUS not only altered endometrial thickness, but--in women with prolonged
      bleedings--also significantly changed uterine artery blood flow. Further studies
      are needed to confirm these results and enable gynecologists to properly counsel
      women, improving initial continuation rates.

PMID- 24868551
TI  - Clusters of adolescent and young adult thyroid cancer in Florida counties.
AB  - BACKGROUND: Thyroid cancer is a common cancer in adolescents and young adults
      ranking 4th in frequency. Thyroid cancer has captured the interest of
      epidemiologists because of its strong association to environmental factors. The
      goal of this study is to identify thyroid cancer clusters in Florida for the
      period 2000-2008. This will guide further discovery of potential risk factors
      within areas of the cluster compared to areas not in cluster. METHODS: Thyroid
      cancer cases for ages 15-39 were obtained from the Florida Cancer Data System.
      Next, using the purely spatial Poisson analysis function in SaTScan, the
      geographic distribution of thyroid cancer cases by county was assessed for
      clusters. The reference population was obtained from the Census Bureau 2010,
      which enabled controlling for population age, sex, and race. RESULTS: Two
      statistically significant clusters of thyroid cancer clusters were found in
      Florida: one in southern Florida (SF) (relative risk of 1.26; P value of <0.001)
      and the other in northwestern Florida (NWF) (relative risk of 1.71; P value of
      0.012). These clusters persisted after controlling for demographics including
      sex, age, race. CONCLUSION: In summary, we found evidence of thyroid cancer
      clustering in South Florida and North West Florida for adolescents and young
      adult.

PMID- 24868550
TI  - Tumor and endothelial cell hybrids participate in glioblastoma vasculature.
AB  - BACKGROUND: Recently antiangiogenic therapy with bevacizumab has shown a high but
      transient efficacy in glioblastoma (GBM). Indeed, GBM is one of the most
      angiogenic human tumors and endothelial proliferation is a hallmark of the
      disease. We therefore hypothesized that tumor cells may participate in
      endothelial proliferation of GBM. MATERIALS AND METHODS: We used EGFR FISH Probe
      to detect EGFR amplification and anti-CD31, CD105, VE-cadherin, and vWF to
      identify endothelial cells. Endothelial and GBM cells were grown separately,
      labeled with GFP and DsRed lentiviruses, and then cocultured with or without
      contact. RESULTS: In a subset of GBM tissues, we found that several tumor
      endothelial cells carry EGFR amplification, characteristic of GBM tumor cells.
      This observation was reproduced in vitro: when tumor stem cells derived from GBM
      were grown in the presence of human endothelial cells, a fraction of them
      acquired endothelial markers (CD31, CD105, VE-cadherin, and vWF). By transduction
      with GFP and DsRed expressing lentiviral vectors, we demonstrate that this
      phenomenon is due to cell fusion and not transdifferentiation. CONCLUSION: A
      fraction of GBM stem cells thus has the capacity to fuse with endothelial cells
      and the resulting hybrids may participate in tumor microvascular proliferation
      and in treatment resistance.

PMID- 24868553
TI  - In vitro larvicidal and antioxidant activity of dihydrophenanthroline-3
      carbonitriles.
AB  - Many naturally occurring and synthetic compounds containing dihydrocyanopyridine
      and cyanopyran moiety show pharmacological properties. The aim of this study is
      to investigate the larvicidal and antioxidant potential of dihydrophenanthroline
      3-carbonitrile derivatives 4a-f. A novel series of 2-amino-10-chloro-4,12
      diphenyl-1,4,5,6-tetrahydrobenzo[j][1,7]phenanthroline-3-carbonitrile derivatives
      were synthesized by reacting different substituted acridine chalcones through
      Michel addition. The compounds were synthesized in excellent yields and the
      structures were corroborated on the basis of FT-IR, 1H NMR, 13C NMR, and ESI Mass
      analysis data. All the synthesized compounds were evaluated for larvicidal
      activity against Aedes aegypti and Culex quinquefasciatus larvae. Furthermore,
      the antioxidant activity was studied by the 1,1-diphenyl-2-picrylhydrazyl (DPPH)
      assay method. From the antioxidant assay, the compound 4c was reported with
      profound antioxidant potential.

PMID- 24868552
TI  - The multifaceted functions of CXCL10 in cardiovascular disease.
AB  - C-X-C motif ligand 10 (CXCL10), or interferon-inducible protein-10, is a small
      chemokine belonging to the CXC chemokine family. Its members are responsible for
      leukocyte trafficking and act on tissue cells, like endothelial and vascular
      smooth muscle cells. CXCL10 is secreted by leukocytes and tissue cells and
      functions as a chemoattractant, mainly for lymphocytes. After binding to its
      receptor CXCR3, CXCL10 evokes a range of inflammatory responses: key features in
      cardiovascular disease (CVD). The role of CXCL10 in CVD has been extensively
      described, for example for atherosclerosis, aneurysm formation, and myocardial
      infarction. However, there seems to be a discrepancy between experimental and
      clinical settings. This discrepancy occurs from differences in biological actions
      between species (e.g. mice and human), which is dependent on CXCL10 signaling via
      different CXCR3 isoforms or CXCR3-independent signaling. This makes translation
      from experimental to clinical settings challenging. Furthermore, the overall
      consensus on the actions of CXCL10 in specific CVD models is not yet reached. The
      purpose of this review is to describe the functions of CXCL10 in different CVDs
      in both experimental and clinical settings and to highlight and discuss the
      possible discrepancies and translational difficulties. Furthermore, CXCL10 as a
      possible biomarker in CVD will be discussed. 

PMID- 24868555
TI  - Biomarkers of type II synthetic pyrethroid pesticides in freshwater fish.
AB  - Type II synthetic pyrethroids contain an alpha-cyano group which renders them
      more neurotoxic than their noncyano type I counterparts. A wide array of
      biomarkers have been employed to delineate the toxic responses of freshwater fish
      to various type II synthetic pyrethroids. These include hematological, enzymatic,
      cytological, genetic, omic and other types of biomarkers. This review puts
      together the applications of different biomarkers in freshwater fish species in
      response to the toxicity of the major type II pyrethroid pesticides and assesses
      their present status, while speculating on the possible future directions. 

PMID- 24868554
TI  - The E3 ligase CHIP: insights into its structure and regulation.
AB  - The carboxy-terminus of Hsc70 interacting protein (CHIP) is a cochaperone E3
      ligase containing three tandem repeats of tetratricopeptide (TPR) motifs and a C
      terminal U-box domain separated by a charged coiled-coil region. CHIP is known to
      function as a central quality control E3 ligase and regulates several proteins
      involved in a myriad of physiological and pathological processes. Recent studies
      have highlighted varied regulatory mechanisms operating on the activity of CHIP
      which is crucial for cellular homeostasis. In this review article, we give a
      concise account of our current knowledge on the biochemistry and regulation of
      CHIP. 

PMID- 24868557
TI  - Splanchnicectomy for pancreatic cancer pain.
AB  - Persistent pain is a serious problem that often contributes to a poor quality of
      life in pancreatic cancer patients. Medical management by opioid analgesics is
      often accompanied by side effects and incomplete pain relief. A celiac plexus
      block is a simple treatment which relieves pain, but the procedure demands a
      certain degree of proficiency and the duration of the effects obtained can be
      rather limited. Transhiatal bilateral splanchnicectomy achieves a certain
      denervation of splanchnic nerves, but it requires a laparotomy. Unilateral
      thoracoscopic splanchnicectomy is a minimally invasive procedure to cause
      definite denervation. Bilateral thoracoscopic splanchnicectomy is recommended for
      unsatisfactory cases or recurrent pain occurring after the initial unilateral
      splanchnicectomy. It is important to select the most suitable treatment depending
      on patients' actual medical state and the predicted outcomes. 

PMID- 24868556
TI  - Recent concepts of ovarian carcinogenesis: type I and type II.
AB  - Type I ovarian tumors, where precursor lesions in the ovary have clearly been
      described, include endometrioid, clear cell, mucinous, low grade serous, and
      transitional cell carcinomas, while type II tumors, where such lesions have not
      been described clearly and tumors may develop de novo from the tubal and/or
      ovarian surface epithelium, comprise high grade serous carcinomas,
      undifferentiated carcinomas, and carcinosarcomas. The carcinogenesis of
      endometrioid and clear cell carcinoma (CCC) arising from endometriotic cysts is
      significantly influenced by the free iron concentration, which is associated with
      cancer development through the induction of persistent oxidative stress. A subset
      of mucinous carcinomas develop in association with ovarian teratomas; however,
      the majority of these tumors do not harbor any teratomatous component. Other
      theories of their origin include mucinous metaplasia of surface epithelial
      inclusions, endometriosis, and Brenner tumors. Low grade serous carcinomas are
      thought to evolve in a stepwise fashion from benign serous cystadenoma to a
      serous borderline tumor (SBT). With regard to high grade serous carcinoma, the
      serous tubal intraepithelial carcinomas (STICs) of the junction of the fallopian
      tube epithelium with the mesothelium of the tubal serosa, termed the "tubal
      peritoneal junction" (TPJ), undergo malignant transformation due to their
      location, and metastasize to the nearby ovary and surrounding pelvic peritoneum.
      Other theories of their origin include the ovarian hilum cells. 

PMID- 24868559
TI  - The associations between VEGF gene polymorphisms and diabetic retinopathy
      susceptibility: a meta-analysis of 11 case-control studies.
AB  - AIMS. Published data on the associations of VEGF polymorphisms with diabetic
      retinopathy (DR) susceptibility are inconclusive. A systematic meta-analysis was
      undertaken to clarify this topic. METHODS. Data were collected from the following
      electronic databases: PubMed, Embase, OVID, Web of Science, Elsevier Science
      Direct, Excerpta Medica Database (EMBASE), and Cochrane Library with the last
      report up to January 10, 2014. ORs and 95% CIs were calculated for VEGF-2578C/A
      (rs699947), -1154G/A (rs1570360), -460T/C (rs833061), -634G>C (rs2010963), and
      +936C/T (rs3025039) in at least two published studies. Meta-analysis was
      performed in a fixed/random effect model by using the software STATA 12.0.
      RESULTS. A total of 11 studies fulfilling the inclusion criteria were included in
      this meta-analysis. A significant relationship between VEGF+936C/T (rs3025039)
      polymorphism and DR was found in a recessive model (OR = 3.19, 95% CI = 1.20
      8.41, and P(z) = 0.01) in Asian and overall populations, while a significant
      association was also found between -460T/C (rs833061) polymorphism and DR risk
      under a recessive model (OR = 2.12, 95% CI = 1.12-4.01, and P(z) = 0.02).
      CONCLUSIONS. Our meta-analysis demonstrates that +936C/T (rs3025039) is likely to
      be associated with susceptibility to DR in Asian populations, and the recessive
      model of -460T/C (rs833061) is associated with elevated DR susceptibility.

PMID- 24868558
TI  - Data mining for identifying novel associations and temporal relationships with
      Charcot foot.
AB  - INTRODUCTION. Charcot foot is a rare and devastating complication of diabetes.
      While some risk factors are known, debate continues regarding etiology.
      Elucidating other associated disorders and their temporal occurrence could lead
      to a better understanding of its pathogenesis. We applied a large data mining
      approach to Charcot foot for elucidating novel associations. METHODS. We
      conducted an association analysis using ICD-9 diagnosis codes for every patient
      in our health system (n = 1.6 million with 41.2 million time-stamped ICD-9
      codes). For the current analysis, we focused on the 388 patients with Charcot
      foot (ICD-9 713.5). RESULTS. We found 710 associations, 676 (95.2%) of which had
      a P value for the association less than 1.0 * 10-5 and 603 (84.9%) of which had
      an odds ratio > 5.0. There were 111 (15.6%) associations with a significant
      temporal relationship (P < 1.0 * 10-3). The three novel associations with the
      strongest temporal component were cardiac dysrhythmia, pulmonary eosinophilia,
      and volume depletion disorder. CONCLUSION. We identified novel associations with
      Charcot foot in the context of pathogenesis models that include neurotrophic,
      neurovascular, and microtraumatic factors mediated through inflammatory
      cytokines. Future work should focus on confirmatory analyses. These novel areas
      of investigation could lead to prevention or earlier diagnosis.

PMID- 24868560
TI  - Regulatory lymphocytes are key factors in MHC-independent resistance to EAE.
AB  - BACKGROUND AND OBJECTIVES: Resistant and susceptible mouse strains to
      experimental autoimmune encephalomyelitis (EAE), an inducible demyelinating
      experimental disease serving as animal model for multiple sclerosis, have been
      described. We aimed to explore MHC-independent mechanisms inducing resistance to
      EAE. METHODS: For EAE induction, female C57BL/6 (susceptible strain) and CD1
      (resistant outbred strain showing heterogeneous MHC antigens) mice were immunized
      with the 35-55 peptide of myelin oligodendrocyte glycoprotein (MOG35-55). We
      studied T cell proliferation, regulatory and effector cell subpopulations,
      intracellular and serum cytokine patterns, and titers of anti-MOG serum
      antibodies. RESULTS: Upon immunization with MOG35-55, T lymphocytes from
      susceptible mice but not that of resistant strain were capable of proliferating
      when stimulated with MOG35-55. Accordingly, resistant mice experienced a rise in
      regulatory B cells (P=0.001) and, to a lower extent, in regulatory T cells
      (P=0.02) compared with C57BL/6 susceptible mice. As a consequence, MOG35-55
      immunized C57BL/6 mice showed higher percentages of CD4+ T cells producing both
      IFN-gamma (P=0.02) and IL-17 (P=0.009) and higher serum levels of IL-17 (P=0.04)
      than resistant mice. CONCLUSIONS: Expansion of regulatory B and T cells
      contributes to the induction of resistance to EAE by an MHC-independent
      mechanism.

PMID- 24868561
TI  - Predicting alloreactivity in transplantation.
AB  - Human leukocyte Antigen (HLA) mismatching leads to severe complications after
      solid-organ transplantation and hematopoietic stem-cell transplantation. The
      alloreactive responses underlying the posttransplantation complications include
      both direct recognition of allogeneic HLA by HLA-specific alloantibodies and T
      cells and indirect T-cell recognition. However, the immunogenicity of HLA
      mismatches is highly variable; some HLA mismatches lead to severe clinical B-cell
      and T-cell-mediated alloreactivity, whereas others are well tolerated.
      Definition of the permissibility of HLA mismatches prior to transplantation
      allows selection of donor-recipient combinations that will have a reduced chance
      to develop deleterious host-versus-graft responses after solid-organ
      transplantation and graft-versus-host responses after hematopoietic stem-cell
      transplantation. Therefore, several methods have been developed to predict
      permissible HLA-mismatch combinations. In this review we aim to give a
      comprehensive overview about the current knowledge regarding HLA-directed
      alloreactivity and several developed in vitro and in silico tools that aim to
      predict direct and indirect alloreactivity. 

PMID- 24868564
TI  - Prospective randomized contralateral eye evaluation of subjective quality of
      vision after wavefront-guided or wavefront- optimized photorefractive
      keratectomy.
AB  - PURPOSE: To compare the effect of wavefront-guided (WFG) and wavefront-optimized
      (WFO) photorefractive keratectomy (PRK) on patient perceived quality of vision.
      METHODS: Seventy-one patients (142 eyes) were enrolled in this prospective,
      randomized, fellow eye controlled study. One eye was randomized to undergo WFG
      PRK treatment by the AMO Visx CustomVue S4 IR excimer laser system (Abbott
      Medical Optics, Inc., Santa Clara, CA) and the fellow eye received WFO PRK
      treatment by the Alcon Allegretto Wave Eye-Q 400 Hz excimer laser system (Alcon
      Laboratories, Inc., Fort Worth, TX). Patients answered questionnaires on their
      visual symptoms and quality of vision preoperatively and at 1, 3, 6, and 12
      months after surgery. RESULTS: Patients in both groups reported better vision
      compared to baseline from 3 months onward (mean change in score of 1.56 to 2.51
      in the WFO group and 1.54 to 2.28 in the WFG group, P ? .003). Both groups
      experienced less nighttime glare from 6 months onward (P ? .030). Halos, double
      vision, and visual clarity were initially worse (P ? .025) but not significantly
      different after 1 month. Haze and fluctuating vision resolved after 3 months.
      Visual symptoms were similar between the two groups at all times (P ? .059)
      except at 6 months, when patients felt their WFG eyes had more excellent vision
      (P = .029). A composite of all symptoms was also similar between the groups until
      12 months when patients had fewer symptoms in their WFO eye (P = .044).
      CONCLUSIONS: One year after surgery, patient self-reported visual symptoms were
      not significantly different in eyes receiving WFG or WFO PRK. However, the
      average of all symptoms was lower in eyes receiving wavefront-optimized
      treatment.

PMID- 24868562
TI  - Selective depletion of regulatory T cell subsets by docetaxel treatment in
      patients with nonsmall cell lung cancer.
AB  - Regulatory T (Treg) cells are potent suppressors that maintain immune
      homeostasis. Accumulation of Treg can inhibit effective immune responses in
      cancer patients, leading to tumor development and progression. Despite direct
      cytotoxicity, several chemotherapeutic drugs have been reported to deplete Treg
      cells for better prognosis for cancer patients. Treg cells are a heterogenous
      population with at least three different subsets, nonsuppressive, resting, and
      activated Treg cells. However, the characteristics of Treg cell subsets in lung
      cancer patients and how chemotherapy affects Treg cells remain elusive. In this
      study, we first analyzed Treg cell subsets in peripheral blood samples from 40
      nonsmall cell lung cancer (NSCLC) patients and 20 healthy donors. Treg cells,
      specifically activated Treg cell subset, significantly increased in patients with
      NSCLC. Compared to nonsuppressive Treg cells, activated Treg cells expressed
      higher level of CD39 and predominantly produced inhibitory cytokines. In vitro
      assay showed that docetaxel reduced all three subsets of Treg cells. More
      importantly, we found docetaxel-based chemotherapy significantly decreased all
      three Treg subsets after 4 cycles of treatment in 17 NSCLC patients. Taken
      together, this study revealed dynamic changes of various Treg cell subsets in
      NSCLC patients before and after chemotherapy, providing activated Treg cells as a
      potential target for chemotherapy. 

PMID- 24868565
TI  - Citrate content of bone for time since death estimation: results from burials
      with different physical characteristics and known PMI.
AB  - A recently introduced method to determine the postmortem interval (PMI) based on
      quantification of the citrate content in bone was applied on the temporal bones
      and femora of 20 individuals buried in wooden coffins (WO) and body bags (BB),
      respectively. Concerning known vs. calculated PMI, a significant difference
      between the temporal and the femur bone samples of the same individuals was
      observed in the BB group (p = 0.012). In contrast, differences were insignificant
      for the WO group (p = 0.400). Moreover, similar levels of underestimation of PMIs
      resulted from the analysis of the femora for both burial groups (p = 0.247).
      Also, there was consistently less citrate preserved in the flat temporal bones as
      compared to the femora, indicating that the cortical layer of the long bones
      should be preferentially employed for citrate-based PMI estimations. The results
      call for additional research on subsurface-buried and surface-deposited remains
      to enhance the accuracy of the published PMI equation.

PMID- 24868566
TI  - MERS-CoV enigma deepens as reported cases surge.

PMID- 24868567
TI  - Reply to Desai and   Gillett-Heacock.

PMID- 24868568
TI  - Kidney disease in farming communities remains a mystery.

PMID- 24868569
TI  - Profile: KEMRI-Wellcome Trust Programme celebrates 25 years.

PMID- 24868563
TI  - Current concepts and future directions for the assessment of autoantibodies to
      cellular antigens referred to as anti-nuclear antibodies.
AB  - The detection of autoantibodies that target intracellular antigens, commonly
      termed anti-nuclear antibodies (ANA), is a serological hallmark in the diagnosis
      of systemic autoimmune rheumatic diseases (SARD). Different methods are available
      for detection of ANA and all bearing their own advantages and limitations. Most
      laboratories use the indirect immunofluorescence (IIF) assay based on HEp-2 cell
      substrates. Due to the subjectivity of this diagnostic platform, automated
      digital reading systems have been developed during the last decade. In addition,
      solid phase immunoassays using well characterized antigens have gained widespread
      adoption in high throughput laboratories due to their ease of use and open
      automation. Despite all the advances in the field of ANA detection and its
      contribution to the diagnosis of SARD, significant challenges persist. This
      review provides a comprehensive overview of the current status on ANA testing
      including automated IIF reading systems and solid phase assays and suggests an
      approach to interpretation of results and discusses meeting the problems of assay
      standardization and other persistent challenges. 

PMID- 24868570
TI  - When kidneys fail.

PMID- 24868571
TI  - Richard John Cremer.

PMID- 24868572
TI  - Obituary: Professor Roger Nordmann.

PMID- 24868574
TI  - The Transactions in transition.

PMID- 24868573
TI  - Projected inhibition of  platelet aggregation with  ticagrelor twice daily vs. 
      clopidogrel once daily based  on patient adherence data  (the TWICE project).
AB  - AIM: Twice daily dosing is often perceived as inferior to once daily dosing due
      to a higher likelihood of missing a dose. However, more important is the extent
      to which drug action is maintained when doses are delayed or missed. We compared
      the estimated inhibition of platelet aggregation (eIPA) for ticagrelor twice
      daily and clopidogrel once daily, based on their pharmacokinetic/ pharmacodynamic
      relationships and patient dosing history data. METHODS: Drug dosing histories of
      5014 patients prescribed cardiovascular medications (primarily antihypertensive
      medicines) were extracted from an electronically compiled dosing history
      database. eIPA levels were simulated for 677 twice daily and 677 once daily
      dosing histories over a 30 day period, based on published onset/offset models for
      ticagrelor and clopidogrel IPA characteristics. RESULTS: While many patients
      treated twice daily missed at least one dose in 30 days, only 25.7% missed two
      consecutive doses. By comparison, 46.8% of patients treated once daily missed at
      least one dose. Simulations based on patient adherence over time showed that the
      average mean eIPA for ticagrelor twice daily remained significantly higher than
      for clopidogrel once daily (81.1% vs. 55.0%, P < 0.001). Ticagrelor twice daily
      patients had an eIPA below 10% for 0.20% of the 30 day period compared with 2.05%
      for clopidogrel once daily (P = 0.0001). CONCLUSIONS: The projected level of
      platelet inhibition remained higher for ticagrelor twice daily than clopidogrel
      once daily, mainly due to the higher eIPA level achieved with ticagrelor and the
      relatively low likelihood of missing two consecutive twice daily doses. This
      modelling and simulation study suggests a therapeutic benefit of ticagrelor over
      clopidogrel when taking into account the most common dosing omissions.

PMID- 24868575
TI  - Defining a therapeutic window for the novel TGF-beta inhibitor LY2157299
      monohydrate based on a pharmacokinetic/pharmacodynamic model.
AB  - AIMS: To identify prospectively a safe therapeutic window for administration of a
      novel oral transforming growth factor beta (TGF-beta) inhibitor, LY2157299
      monohydrate, based on a pharmacokinetic/pharmacodynamic (PK/PD) model.
      Simulations of population plasma exposures and biomarker responses in tumour were
      performed for future trials of LY2157299 in glioblastoma and other cancer
      populations. METHODS: The model was updated after completion of each cohort
      during the first-in-human dose (FHD) study. The flexible design allowed
      continuous assessment of PK variability by recruiting the required number of
      patients in each cohort. Based on 30% inhibition of TGF-beta RI kinase
      phosphorylates (pSMAD), biologically effective exposures were anticipated to be
      reached from 160 mg onwards. The therapeutic window was predicted, based on
      animal data, to be between 160 and 360 mg. RESULTS: No medically significant
      safety issues were observed and no dose limiting toxicities were established in
      this study. Observed plasma exposures (medians 2.43 to 3.7 mg l-1 h,
      respectively) with doses of 160 mg to 300 mg were within the predicted
      therapeutic window. Responses, based on the MacDonald criteria, were observed in
      these patients. CONCLUSIONS: A therapeutic window for the clinical investigation
      of LY2157299 in cancer patients was defined using a targeted PK/PD approach,
      which integrated translational biomarkers and preclinical toxicity. The study
      supports using a therapeutic window based on a PK/PD model in early oncology
      development.

PMID- 24868577
TI  - Response by authors of the original article.

PMID- 24868576
TI  - Epidemiology and potential risk factors of drug-related problems in Hong Kong
      paediatric wards.
AB  - AIMS: A drug-related problem (DRP) is 'an event or circumstance involving drug
      therapy that actually or potentially interferes with the desired health outcome'.
      The extent and characteristics of DRPs in children in Hong Kong are unknown. The
      aim of this study was to determine the epidemiology of and identify riskf actors
      for DRPs in hospitalized children in Hong Kong. METHODS: This was a prospective
      cohort study in children aged 0-18 years who were admitted to a medical ward,
      paediatric intensive care unit or neonatal intensive care unit of seven Hong Kong
      hospitals, during a 3 month period. Patients' charts, medical records and
      laboratory data were reviewed daily to identify DRPs; their preventability and
      severity were assessed. Logistic regression was used to analyse potential risk
      factors associated with the incidence of DRPs. RESULTS: Three hundred and twenty
      nine children (median age, 2 years; interquartile range, 0 months to 9 years)
      were included. In total, 82 DRPs were experienced by 69 patients. The overall
      incidence of DRPs was 21.0% (95% confidence interval, 16.7-25.8%). The incidence
      was higher in neonatal and paediatric intensive care units than medical wards.
      Dosing problems were the most frequently reported DRPs (n = 35; 42.7%), followed
      by drug choice problems (n = 19; 23.2%) and adverse drug reactions (n = 11;
      13.4%). Sixty-seven (81.7%) DRP cases were assessed as preventable, 42 (51.2%) as
      minor and 40 (48.8%) as moderate. The number of prescribed drugs and 'certain
      infectious and parasitic diseases' were potential risk factors for occurrence of
      DRPs. CONCLUSIONS: Drug-related problems were common in hospitalized children in
      this study in Hong Kong; the most frequent were dosing and drug choice problems,
      and the majority of them were preventable. Polypharmacy and 'certain infectious
      and parasitic diseases' were potential risk factors.

PMID- 24868579
TI  - Reply by the authors of the original article.

PMID- 24868578
TI  - Association between  Clostridium difficile infection  and antimicrobial usage in 
      a large group of English  hospitals.
AB  - AIMS: This study aimed to determine the association between the reduction in the
      number of Clostridium difficile infection (CDI) cases reported by the English
      National Health Service (NHS) hospitals and concurrent antimicrobial use.
      METHODS: A retrospective ecological study for January 2005 to December 2008 was
      conducted using data from 26 of the 29 NHS trusts (i.e. a trust manages one or
      more hospitals) located in the North West Strategic Health Authority of England.
      Antimicrobial use data, for patients of all ages, were provided by IMS Health,
      and CDI case data for patients aged >=65 years were provided by the Health
      Protection Agency. Antimicrobial use was converted into defined daily doses
      (DDDs). The overall association between antimicrobial use and CDI for the trusts
      was investigated using multilevel models. RESULTS: Our study shows a positive
      significant association between the CDI cases and the use of the following
      antimicrobials: 'third-generation cephalosporins' [11.62 CDI cases per 1000 DDDs;
      95% confidence interval (CI), 5.92-17.31]; 'fluoroquinolones' (4.79 CDI cases per
      1000 DDDs; 95% CI, 2.83-6.74); and 'second-generation cephalosporins' (4.25 CDI
      cases per 1000 DDDs; 95% CI, 1.66-6.83). The strength of this association was not
      significantly different (95% CI) among the antimicrobial groups. CONCLUSIONS:
      This study shows that the reduction in the number of CDI cases reported by the
      English NHS hospitals is associated with concurrent reductions in antimicrobial
      use. This means that the number of CDI cases over time decreased in a similar
      fashion to the usage of various antimicrobials.

PMID- 24868580
TI  - [Especially vulnerable  workers: a proposal for action].

PMID- 24868581
TI  - A new snapshot hyperspectral imaging system to image optic nerve head tissue.

PMID- 24868582
TI  - Intra-arterial chemotherapy for retinoblastoma. Challenges of a prospective
      study.
AB  - PURPOSE: To report the efficacy and complications of intra-ophthalmic artery
      melphalan (IAM) for treatment of patients with advanced intra-ocular
      retinoblastoma. METHODS: Patients with newly diagnosed, unilateral, group D
      retinoblastoma were included in a phase II protocol. Children with relapsed
      refractory disease after systemic chemoreduction were later treated under the
      same guidelines.Melphalan (3-5 mg/procedure) was injected through a 1.2 F
      microcatheter placed into the ophthalmic artery every 21 days. RESULTS: Eleven
      patients (12 eyes, eight as primary treatment) received 33 IAM procedures. The
      phase II protocol closed prematurely because of low accrual. The IAM technique
      was overall safe and could be performed successfully in 31 of 33(94%) attempts.
      After the second administration of IAM, very good partial response was achieved
      in all treated eyes. With a median follow-up time of 29.5 months (range 6-57),
      ocular salvage was achieved in 7 of 12 (58%) eyes. No systemic adverse events
      were observed. Two patients developed diffuse arteriolar sclerosis,
      hyperpigmentation of the retinal pigment epithelium and partial retinal atrophy
      after the second IAM. Both eyes were preserved with no tumour activity, good
      motility and perception of light, 56 and 30 months after the last IAM treatment.
      Multinucleated macrophages with intracytoplasmic foreign material were found in
      the choroid and the retina in 2 of 5 enucleated eyes. CONCLUSION: Our study
      reports the activity and reproducibility of IAM in advanced retinoblastoma but
      also underlines the challenges of performing prospective studies on this
      treatment modality. Toxicity was limited to only ocular vascular events.

PMID- 24868583
TI  - Therapeutic efficacy of topical unoprostone isopropyl in retinitis pigmentosa.
AB  - PURPOSE: To evaluate the therapeutic effect of topical unoprostone isopropyl
      (unoprostone) on patients with retinitis pigmentosa (RP). METHODS: Forty patients
      with typical forms of RP were included in the study.Seventeen of 40 patients were
      treated with 0.12% topical unoprostone twice daily in a randomly selected eye.
      Patients underwent follow-up examinations every 3 months after treatment. The
      efficacy of the treatment was monitored by visual acuity and visual field
      measurement testing using the Humphrey Field Analyzer (HFA: the central 10-2
      programme). Moreover, 12 RP patients who were included this study and 12 normal
      subjects were evaluated in terms of their macular blood flow of both eyes after
      instillation of unoprostone using the laser speckle method. RESULTS: One year
      after treatment, the 'macular sensitivity', calculated by HFA as the average
      sensitivity of the central 12 points, was preserved in the fellow eyes as well as
      the unoprostone-treated eyes. On the other hand, that in the eyes of the control
      RP patient was significantly decreased. Moreover, there were significantly
      greater improvements of the 'macular sensitivity' in the unoprostone-treated eyes
      than the fellow eyes. The change ratios of macular blood flow obtained from both
      RP patients and normal subjects were significantly increased in both the treated
      and the fellow eyes. No severe side-effects were observed. CONCLUSIONS: These
      results demonstrate that topical unoprostone might have a therapeutic efficacy in
      patients with RP as a consequence of the macular bloodflow improvement as well as
      its direct neuroprotective effect.

PMID- 24868584
TI  - HCO3- secretion by SLC26A3 and mucosal defence in the colon.

PMID- 24868585
TI  - pH-regulated formation of side products in the reductive amination approach for
      differential labeling of peptides in relative quantitative experiments.
AB  - Among the most common stable-isotope labeling strategies, the reaction of
      formaldehyde with peptides in the presence of NaCNBH3 features many attractive
      aspects that are conducive to its employment in quantitation experiments in
      proteomics. Reductive amination, with formaldehyde and d(2)-formaldehyde, is
      reported to be a fast, easy, and specific reaction, undoubtedly inexpensive if
      compared with commercially available kits for differential isotope coding.
      Acetaldehyde and d(4)-acetaldehyde could be employed as well without a
      substantial increase in terms of cost, and should provide a wider spacing between
      the differentially tagged peptides in the mass spectrum. Nevertheless, only a
      single paper reports about a diethylation approach for quantitation. We undertook
      a systematic analytical investigation on the reductive amination of some standard
      peptides pointing out the occasional occurrence of side reactions in dependence
      of pH or reagents order of addition, particularly observing the formation of
      cyclic adducts ascribable to rearrangements involving the generated Schiff-base
      and all the nucleophilic sites of its chemical environment. We also tried to
      evaluate how much this side-products amount may impair isotope coded relative
      quantitation.

PMID- 24868586
TI  - Buffer salt effects in off-line coupling of capillary electrophoresis and mass
      spectrometry.
AB  - In this work, the impact of buffer salts/matrix effects on the signal in direct
      injection MS with an electrospray interface (DI-ESI-MS) following pITP
      fractionation of the sample was studied. A range of buffers frequently used in CE
      analyses (pH 3-10) was prepared containing 10, 50, and 90% v/v of ACN,
      respectively. The sets of calibration solutions of cetirizine (an antihistaminic
      drug with an amphiprotic character) within a 0.05-2.0 mg/L concentration range
      were prepared in different buffers. The greatest enhancements in the MS signal
      (in terms of change in the slope of the calibration line) were obtained for the
      beta-alanine buffer (pH 3.5) in positive ionization and for the borate buffer (pH
      9.2) in negative ionization, respectively. The procedure was successfully applied
      to the analysis of buserelin (a peptidic drug). The slope of the calibration line
      for solutions containing the beta-alanine buffer with 50% of ACN was 4 times
      higher than for water or urine, respectively. This study clearly demonstrates
      that the buffer salt/matrix effects in an offline combination of pITP and DI-ESI
      MS can also play a positive role, as they can enhance the signal in MS. A similar
      influence of the above effects can also be presumed in the CE techniques combined
      on-line with ESI-MS.

PMID- 24868587
TI  - Impact of interdisciplinary treatment on physical and psychosocial parameters in
      patients with fibromyalgia: results of a randomised trial.
AB  - AIM: Fibromyalgia (FM) is a persistent disorder that can have a devastating
      effect on patients' lives. The purpose of the study was to assess the effects of
      an interdisciplinary treatment for FM on patients' physical and psychosocial
      parameters. METHODS: A randomised controlled clinical trial carried out among 153
      patients. The control group (CG) received standard pharmacological therapy. The
      experimental group (EG) received an interdisciplinary treatment. At baseline and
      6 months after the intervention, participants completed assessment for impact of
      FM in the quality of life, anxiety, depression, coping with pain, social support
      and satisfaction with the treatment. RESULTS: A total of 110 participants
      completed the trial. Six months after the intervention, statistically significant
      improvements in quality of life (p = 0.04), pain (p = 0.03), self-assertiveness
      (p = 0.01), mental self-control (p = 0.05), social support (p = 0.02) and
      satisfaction (p = 0.0001) were observed in the EG. Randomisation to the EG was
      identified as a predictor for improvement. CONCLUSION: An interdisciplinary
      intervention may be appropriate for patients referred to a hospital pain
      management unit.

PMID- 24868588
TI  - [Blunt versus sharp suture needles for preventing percutaneous exposure incidents
      in surgical staff].

PMID- 24868589
TI  - [An interview with Joan Boada].

PMID- 24868590
TI  - [Interventions to promote the wearing of hearing protection].

PMID- 24868592
TI  - [Pre-employment examinations for preventing occupational injury and disease in
      workers].

PMID- 24868591
TI  - [Work-related musculoskeletal diseases: a workshop summary (Menorca Statement
      2011) Centre for Occupational Research in Occupational Health (CiSAL)].

PMID- 24868593
TI  - [An interview with Javier Montero].

PMID- 24868594
TI  - Essential role for the SLK protein kinase in embryogenesis and placental tissue
      development.
AB  - BACKGROUND: Over the past decade, the Ste20-like kinase SLK, has been implicated
      in several signaling processes. SLK repression has been shown to impair cell
      cycle kinetics and inhibit FAK-mediated cell migration. Here, using a gene
      trapped allele, we have generated mice expressing a truncated form of the SLK
      kinase. RESULTS: Our results show that an SLK-LacZ fusion protein is expressed in
      embryonic stem cells and in embryos throughout development. We find that the SLK
      LacZ fusion protein is less efficient at phosphorylating substrates resulting in
      reduced cell proliferation within the embryos and angiogenic defects in the
      placentae of the homozygous mutant animals at embryonic day (E) 12.5. This
      results in marked developmental defects and apoptotic lesions in the embryos by
      E14.5. CONCLUSIONS: Homozygotes expressing the SLK-LacZ fusion protein present
      with an embryonic lethal phenotype occurring between E12.5 and E14.5. Overall, we
      demonstrate a requirement for SLK kinase activity in the developing embryo and
      placenta.

PMID- 24868597
TI  - The author response.

PMID- 24868598
TI  - Narrow band imaging: application for early-stage gastrointestinal neoplasia.
AB  - Narrow-band imaging (NBI) is an imaging technique for endoscopy using optical
      filters to narrow the bandwidth of spectral transmittance. Through this narrow
      spectrum, NBI contrasts surface structure and microvascular architecture of
      various lesions. In this article we focus on the application of NBI for early
      stage neoplasia in the esophagus, stomach and colon with a three-step strategy of
      endoscopic diagnosis: (i) the detection of abnormality; (ii) the differentiation
      between non-neoplasia and neoplasia; and (iii) staging for tumor extension and
      depth of invasion.

PMID- 24868596
TI  - Expression of actin-binding proteins and requirement for actin-depolymerizing
      factor in chick neural crest cells.
AB  - BACKGROUND: Neural crest cells are multipotent cells that migrate extensively
      throughout vertebrate embryos to form diverse lineages. Cell migration requires
      polarized, organized actin networks that provide the driving force for motility.
      Actin-binding proteins that regulate neural crest cell migration are just
      beginning to be defined. RESULTS: We recently identified a number of actin
      associated factors through proteomic profiling of methylated proteins in
      migratory neural crest cells. Here, we report the previously undocumented
      expression pattern of three of these proteins in chick early neural crest
      development: doublecortin (DCX), tropomyosin-1 (TPM-1), and actin depolymerizing
      factor (ADF). All three genes are expressed with varying degrees of specificity
      and intensity in premigratory and migratory neural crest cells, and their
      resulting proteins exhibit distinct subcellular localization in migratory neural
      crest cells. Morpholino knock down of ADF reveals it is required for Sox10 gene
      expression, but minimally important during neural crest migration. CONCLUSIONS:
      Neural crest cells express DCX, TPM-1, and ADF. ADF is necessary during neural
      crest specification, but largely dispensable for migration.

PMID- 24868599
TI  - FTY720 enhances chemosensitivity of colon cancer cells to  doxorubicin and
      etoposide via the modulation of  P-glycoprotein and multidrug resistance protein
      1.
AB  - OBJECTIVE: This study aimed to investigate the effects of FTY720 on inducing cell
      growth inhibition and enhancing the cytotoxicity of anti-cancer drugs in the
      human colon cancer cell line HCT-8 and its multidrug-resistant cell line HCT-8/5
      fluorouracil (HCT-8/5-Fu). METHODS: Cell viability and apoptosis after being
      treated with FTY720 alone or in combination with doxorubicin (DOX) and etoposide
      (VP16) were tested in HCT-8 and HCT-8/5-Fu cells. The changes in P-glycoprotein
      (P-gp) and multidrug resistance protein 1 (MRP1) were determined at the mRNA and
      functional levels. RESULTS: FTY720 showed anti-proliferative activity against
      cancer cells in a dose-dependent and time-dependent manner and could enhance the
      cytotoxicity of DOX and VP16 in both HCT-8 and HCT-8/5-Fu cell lines. In
      addition, treatment with FTY720 resulted in the promotion of VP16-induced cell
      apoptosis and an increased accumulation of intracellular DOX and two specific
      fluorescent substrates of P-gp and MRP1 through the inhibition of efflux and the
      suppression of gene expression. CONCLUSION: FTY720 exerts its chemosensitization
      effect in HCT-8 and HCT-8/5-Fu cell lines by promoting cell apoptosis and
      inhibiting P-gp and MRP1, which could be applied as a potential co-adjuvant
      therapeutic modality.

PMID- 24868595
TI  - Left atrial ligation alters intracardiac flow patterns and the biomechanical
      landscape in the chick embryo.
AB  - BACKGROUND: Hypoplastic left heart syndrome (HLHS) is a major human congenital
      heart defect that results in single ventricle physiology and high mortality.
      Clinical data indicate that intracardiac blood flow patterns during cardiac
      morphogenesis are a significant etiology. We used the left atrial ligation (LAL)
      model in the chick embryo to test the hypothesis that LAL immediately alters
      intracardiac flow streams and the biomechanical environment, preceding
      morphologic and structural defects observed in HLHS. RESULTS: Using fluorescent
      dye injections, we found that intracardiac flow patterns from the right common
      cardinal vein, right vitelline vein, and left vitelline vein were altered
      immediately following LAL. Furthermore, we quantified a significant ventral shift
      of the right common cardinal and right vitelline vein flow streams. We developed
      an in silico model of LAL, which revealed that wall shear stress was reduced at
      the left atrioventricular canal and left side of the common ventricle.
      CONCLUSIONS: Our results demonstrate that intracardiac flow patterns change
      immediately following LAL, supporting the role of hemodynamics in the progression
      of HLHS. Sites of reduced WSS revealed by computational modeling are commonly
      affected in HLHS, suggesting that changes in the biomechanical environment may
      lead to abnormal growth and remodeling of left heart structures.

PMID- 24868600
TI  - Providers need to boost efforts to prevent abuse of narcotics.

PMID- 24868601
TI  - Pharmacy benefit management in the new world of ACOs.

PMID- 24868602
TI  - Thoughts on the future of peer-run services: part 1.

PMID- 24868603
TI  - Sizing up 'superfoods' for heart health. Many foods--from the everyday to the
      exotic--are rich in nutrients that may help keep your arteries clear and your
      heartbeat stable.

PMID- 24868604
TI  - Ask the doctor. The June 2013 issue states on page 3 that "it's important to
      increase potassium intake, particularly if you take a diuretic." But on page 5,
      it says that if you take spironolactone (which I do), you should avoid high
      potassium foods. I'm confused--should I be eating bananas and other potassium
      rich foods or not?

PMID- 24868605
TI  - Ask the doctor. I was having occasional chest pains, and my primary care
      physician recommended a stress test. Because I have bad knees, the cardiologist
      had me take a stress test using a medication instead of doing exercise.
      Fortunately, the results were normal. But it made me wonder: is one type better
      than the other?

PMID- 24868606
TI  - 5 action steps for early heart failure. Early heart failure may be mild but can
      worsen quickly. Learn what you can do to keep symptoms in check.

PMID- 24868607
TI  - New techniques for treating Afib. New devices and treatments can help prevent
      irregular atrial heart rhythms and related risks.

PMID- 24868608
TI  - Borderline hypertension. When do you need treatment? Many people develop high
      blood pressure during their lifetime. These steps may delay your need to take
      medicines.

PMID- 24868609
TI  - Understanding angioplasty: When you need it--and when you may not. Angioplasty
      can save lives, but it isn't always urgent. For some people, optimal medical
      therapy makes sense.

PMID- 24868610
TI  - Stroke and migraine: What's the link?

PMID- 24868611
TI  - Vitamin supplements no help against heart disease.

PMID- 24868612
TI  - Memory loss from statins unlikely.

PMID- 24868613
TI  - Taking steps to avoid heart disease.

PMID- 24868614
TI  - Using acetaminophen safely.

PMID- 24868615
TI  - Mending spinal compression fractures. Johns Hopkins experts compare surgical and
      nonsurgical fixes.

PMID- 24868616
TI  - Tinnitus treatments: breaking through the noise.

PMID- 24868617
TI  - [Diabetic mycosis intertrigo and onychomycosis].

PMID- 24868618
TI  - [An interview with Oriana Ramirez-Rubio].

PMID- 24868619
TI  - [European agency for safety and health at work].

PMID- 24868620
TI  - [News from the Generalitat of Catalonia].

PMID- 24868622
TI  - [European agency for safety and health at work].

PMID- 24868621
TI  - [News from the Generalitat of Catalonia].

PMID- 24868623
TI  - [News from the Generalitat of Catalonia].

PMID- 24868624
TI  - Case law update. Cruz-Vazquez v Mennonite General Hospital, No. 11-2297  (1st Cir
      May 29, 2013).

PMID- 24868625
TI  - Case law update. Kowalski v St. Francis Hospital & Health Centers , 2013 NY Slip
      Op 04756 (NY June 26, 2013).

PMID- 24868626
TI  - Case law update. United States v Gonzales-Ramos , Case No. 2:13-cr-00105  (SD W
      Va September 3, 2013).

PMID- 24868627
TI  - Case law update. Torres v Santa Rosa Memorial Hospital , No. C 12-6364  PJH (ND
      Calif August 20, 2013).

PMID- 24868628
TI  - Your pension, your pay, your NHS.

PMID- 24868629
TI  - The pivotal role of workplace representatives.

PMID- 24868630
TI  - When things go boom.

PMID- 24868631
TI  - Zero tolerance needed to wipe out FGM.

PMID- 24868632
TI  - Meet the president.

PMID- 24868633
TI  - Are you involved?

PMID- 24868634
TI  - Mistakes spotted on Call the Midwife.

PMID- 24868635
TI  - Acupuncture treatment for hyperemesis gravidarum.

PMID- 24868636
TI  - Blackburn Birth Centre.

PMID- 24868637
TI  - Keeping up the pace.

PMID- 24868638
TI  - Hand expression versus breast pumping.

PMID- 24868639
TI  - ...Encourage a woman to remain active in labour.

PMID- 24868640
TI  - Weathering the storm. Birth forecasting in turbulent times.

PMID- 24868641
TI  - Money matters.

PMID- 24868642
TI  - Another questionable procedure for maternity services?

PMID- 24868643
TI  - Trusted allies.

PMID- 24868644
TI  - Kangaroo care on the postnatal ward.

PMID- 24868646
TI  - NMC hikes annual fee to pound100.

PMID- 24868645
TI  - Serving our members.

PMID- 24868647
TI  - Momentum gains in numbers.

PMID- 24868648
TI  - Midwives and disciplinary proceedings.

PMID- 24868649
TI  - Calculating the risk.

PMID- 24868650
TI  - A rounded education.

PMID- 24868651
TI  - NMC registration.

PMID- 24868652
TI  - A brave voice.

PMID- 24868653
TI  - Lost in translation.

PMID- 24868654
TI  - Fear of childbirth and duration of labour.

PMID- 24868655
TI  - How to ... test for glucose intolerance.

PMID- 24868657
TI  - Safety in service.

PMID- 24868656
TI  - Facing the future. What will the NHS look like under Hunt?

PMID- 24868658
TI  - Tackling the deficiency.

PMID- 24868659
TI  - Hitting performance targets.

PMID- 24868660
TI  - An evolving role.

PMID- 24868661
TI  - Under the spotlight.

PMID- 24868662
TI  - Branching out.

PMID- 24868663
TI  - Making the right choices.

PMID- 24868664
TI  - Privatisation of midwifery?

PMID- 24868665
TI  - Times have changed... for the worse.

PMID- 24868666
TI  - Midwife memoirs hit the small screen.

PMID- 24868667
TI  - Midwife-led care is safe in Ireland.

PMID- 24868668
TI  - How to... perform a stretch and sweep.

PMID- 24868669
TI  - All part of the equation.

PMID- 24868670
TI  - The age of virtual learning.

PMID- 24868671
TI  - Travelling into the unknown.

PMID- 24868672
TI  - For the record.

PMID- 24868673
TI  - Core strength.

PMID- 24868674
TI  - Delivering in the age of super-diversity.

PMID- 24868675
TI  - Down with the kids.

PMID- 24868676
TI  - Maternity matters in Camden.

PMID- 24868677
TI  - A day in the life of... a labour ward coordinator.

PMID- 24868678
TI  - Picking up the pieces.

PMID- 24868679
TI  - Next on the agenda.

PMID- 24868680
TI  - Wales focuses on maternity issues.

PMID- 24868681
TI  - 'Midwives are angels'.

PMID- 24868682
TI  - Not 'just a student'.

PMID- 24868683
TI  - Reality check.

PMID- 24868684
TI  - One poor depiction.

PMID- 24868685
TI  - Changes in labour patterns over 50 years.

PMID- 24868686
TI  - How to... 'listen' for fetal wellbeing.

PMID- 24868687
TI  - Home birth: a universal fear?

PMID- 24868688
TI  - A binding issue.

PMID- 24868689
TI  - Childbirth myths around the world.

PMID- 24868690
TI  - Raising awareness of group B Strep.

PMID- 24868691
TI  - The fear factor.

PMID- 24868692
TI  - Fathers at birth and beyond.

PMID- 24868693
TI  - Cutting corners.

PMID- 24868694
TI  - Update on postpartum haemorrhage.

PMID- 24868695
TI  - [A look at the bigger picture].

PMID- 24868696
TI  - [An employee unable to provide night care nursing is not generally disabled. The
      Federal Labor Court decides in favor of a nurse].

PMID- 24868697
TI  - [The new nursing care eligibility concept comes to fruition. MDK, GKV and
      scientists start with the new trial phase].

PMID- 24868698
TI  - [The Kohlhammer Forum at the Nursing and Rehabilitation Congress is dedicated to
      selective nursing topics. From music sound massage and acupressure].

PMID- 24868699
TI  - [A nurse reports one year following the end of her education, what her
      professional role is and how she feels about it. "I need time to adjust"
      (interview by Alexander Rose)].

PMID- 24868700
TI  - [Experiences of German nursing students in a health project in Kenya. "Hakuna
      Matata" and reality].

PMID- 24868701
TI  - [Nursing science and nursing research in Germany profit from international
      contacts. Looking at the big picture].

PMID- 24868702
TI  - [Many students and trainees consider spending a few months overseas. An ERASMUS
      representative clarifies what is expected. Global study].

PMID- 24868703
TI  - [Nursing education in Brazil: perspectives and challenges. Autonomy and
      approval].

PMID- 24868704
TI  - [How a Denmark excursion during the master's study curriculum broadens the
      horizon. Across the borders toward the North ].

PMID- 24868705
TI  - [In focus: the Educational Center for Health Sciences & Management at the dual
      Baden-Wurttemberg University. From theory to practice].

PMID- 24868707
TI  - [Communication training in oncology results in more empathy].

PMID- 24868706
TI  - [Polemic pamphlet on the training concept in nursing. No real recognition].

PMID- 24868709
TI  - [First experiments in the possible integration of electric vehicles in urban and
      rural nursing servics. As far as the batteries last].

PMID- 24868708
TI  - [Mentorship in geriatric and patient nursing. Creating practical training].

PMID- 24868711
TI  - [In focus: allocation in health care. Ideal distribution of resources].

PMID- 24868710
TI  - [Welcome to the Jungle].

PMID- 24868712
TI  - [Why the history of nursing as a research field is so important. Reconstructing
      and analyzing].

PMID- 24868713
TI  - The gemini effect.

PMID- 24868714
TI  - A return to regional pay?

PMID- 24868715
TI  - Time for a big push.

PMID- 24868716
TI  - Behind the scenes.

PMID- 24868717
TI  - Men delivering for television.

PMID- 24868718
TI  - US versus UK.

PMID- 24868719
TI  - Mistakes spotted on Call the Midwife.

PMID- 24868720
TI  - Language barrier: my interpretation.

PMID- 24868721
TI  - Positive role of breastfeeding during the first six weeks.

PMID- 24868722
TI  - How to...set up an infusion.

PMID- 24868723
TI  - The impact of a drama.

PMID- 24868724
TI  - Support for those most at need.

PMID- 24868725
TI  - Marketing in maternity.

PMID- 24868726
TI  - Reducing mortality from cervical cancer.

PMID- 24868727
TI  - Balancing the maternity books.

PMID- 24868728
TI  - Seamless service?

PMID- 24868729
TI  - Leadership. What's that got to do with me?

PMID- 24868730
TI  - Staying positive.

PMID- 24868732
TI  - A united fight against FGM.

PMID- 24868731
TI  - Changing childbirth. Challenges the same, 20 years on.

PMID- 24868733
TI  - Presenting the facts.

PMID- 24868735
TI  - A cutting edge experience.

PMID- 24868734
TI  - Hitting the ground running.

PMID- 24868736
TI  - Shocking myths.

PMID- 24868737
TI  - Breech possibilities.

PMID- 24868738
TI  - Embracing mentorship.

PMID- 24868739
TI  - Top 10 tips for qualified midwives.

PMID- 24868740
TI  - Continuity of care vs fragmented care.

PMID- 24868741
TI  - How to... conduct active management of the third stage of labour.

PMID- 24868742
TI  - Removing the risk.

PMID- 24868743
TI  - Engaging hearts and minds.

PMID- 24868744
TI  - Pearls of wisdom.

PMID- 24868745
TI  - Preventing pelvic flaws.

PMID- 24868746
TI  - A risky business.

PMID- 24868747
TI  - Reinventing and engaging.

PMID- 24868748
TI  - The chancellor's tactics.

PMID- 24868749
TI  - FGM helpline. RCM supports charity launch.

PMID- 24868750
TI  - Detention of pregnant immigrants.

PMID- 24868751
TI  - 12-hour shifts: friend or foe?

PMID- 24868752
TI  - The knowledge exchange.

PMID- 24868753
TI  - Left-handed midwifery.

PMID- 24868754
TI  - Timing of initiation of antenatal care.

PMID- 24868755
TI  - How to... undertake a postnatal examination.

PMID- 24868756
TI  - Out of the shadows.

PMID- 24868757
TI  - A united front.

PMID- 24868758
TI  - A dramatic solution.

PMID- 24868759
TI  - Supporting the supervisors.

PMID- 24868760
TI  - MIdwives: the next generation.

PMID- 24868761
TI  - Stop the clot.

PMID- 24868762
TI  - Journey into Africa.

PMID- 24868763
TI  - Student life.

PMID- 24868764
TI  - Risk under the spotlight.

PMID- 24868765
TI  - A year of opportunity.

PMID- 24868766
TI  - Vitamin D study. 'improves muscle strength'.

PMID- 24868767
TI  - 'Let's keep up the pressure'.

PMID- 24868768
TI  - Reflecting on the figures.

PMID- 24868769
TI  - Vital statistics.

PMID- 24868770
TI  - Resolving the fear factor.

PMID- 24868771
TI  - Third stage debate.

PMID- 24868772
TI  - Karen Baker's response.

PMID- 24868773
TI  - Breech delivery.

PMID- 24868774
TI  - Stop the unnecessary suffering.

PMID- 24868775
TI  - A strong foundation.

PMID- 24868776
TI  - Cultural exploration.

PMID- 24868777
TI  - Nut consumption and childhood allergies.

PMID- 24868778
TI  - How to... keep a reflective journal.

PMID- 24868780
TI  - Screening update.

PMID- 24868779
TI  - A cinderella story.

PMID- 24868781
TI  - Natural born killer.

PMID- 24868782
TI  - Community midwives on the go.

PMID- 24868783
TI  - Worth its salt.

PMID- 24868784
TI  - it's in the genes.

PMID- 24868785
TI  - Counting midwives.

PMID- 24868786
TI  - Cutting C-sections.

PMID- 24868787
TI  - A welcome return.

PMID- 24868788
TI  - Religious midwives appeal abortion ruling.

PMID- 24868789
TI  - Changes on the agenda.

PMID- 24868790
TI  - Myth busting.

PMID- 24868791
TI  - Educational value.

PMID- 24868792
TI  - A valuable service.

PMID- 24868793
TI  - Bank midwives.

PMID- 24868795
TI  - Feedback needed.

PMID- 24868796
TI  - Are you involved?

PMID- 24868797
TI  - Children of older mothers.

PMID- 24868798
TI  - ...Suture correctly.

PMID- 24868799
TI  - Outstanding supporting role.

PMID- 24868801
TI  - MSWs and antenatal screening.

PMID- 24868800
TI  - Brand new commission.

PMID- 24868802
TI  - A matter of life or death?

PMID- 24868803
TI  - A lesson learned.

PMID- 24868804
TI  - Smoking ban.

PMID- 24868805
TI  - 'A fundamental culture change is needed'.

PMID- 24868806
TI  - Call the 70-year-old midwife?

PMID- 24868807
TI  - A broader view.

PMID- 24868808
TI  - Sisterly love.

PMID- 24868809
TI  - Religious education.

PMID- 24868810
TI  - Are you involved? Abortion scene controversy.

PMID- 24868811
TI  - Maternal and fetal risk factors for stillbirth.

PMID- 24868812
TI  - How to... provide postnatal perineal care.

PMID- 24868813
TI  - Setting the standard.

PMID- 24868814
TI  - Experiencing induction.

PMID- 24868815
TI  - Measuring results.

PMID- 24868816
TI  - A fine line.

PMID- 24868817
TI  - A meeting of minds.

PMID- 24868819
TI  - Clarity in screening.

PMID- 24868818
TI  - Beyond the pale.

PMID- 24868820
TI  - Spreading the global message.

PMID- 24868821
TI  - Global report on mothers. Congolese mothers have toughest deal.

PMID- 24868823
TI  - Protecting our members.

PMID- 24868822
TI  - The consortium crumbles.

PMID- 24868824
TI  - Selfless dedication.

PMID- 24868825
TI  - The long road to midwifery.

PMID- 24868826
TI  - Fathers reaching out.

PMID- 24868827
TI  - Mutual appreciation.

PMID- 24868828
TI  - Bridge of life.

PMID- 24868829
TI  - Managing perceptions.

PMID- 24868830
TI  - Are you involved?

PMID- 24868831
TI  - Intrapartum interventions and breastfeeding duration.

PMID- 24868832
TI  - How to ... take a newborn blood spot sample.

PMID- 24868833
TI  - Food for thought. The impact of obesity in pregnancy.

PMID- 24868834
TI  - A sustainable service.

PMID- 24868835
TI  - A close comparison.

PMID- 24868836
TI  - Healthy babies, hopeful hearts.

PMID- 24868837
TI  - A world of difference.

PMID- 24868838
TI  - Access Nepal.

PMID- 24868839
TI  - Looking forward. Trends in operating room procedures in the U.S.

PMID- 24868840
TI  - Liability reforms needed to provide timely care to disaster victims.

PMID- 24868841
TI  - International Guest Scholarships: an investment in surgical training around the
      globe.

PMID- 24868842
TI  - Implementation of the ACA: turning federal law into state-level reality.

PMID- 24868843
TI  - Vascular practice develops night float call system to improve attending well
      being without decreasing productivity.

PMID- 24868844
TI  - Billing for services performed by nonphysician practitioners.

PMID- 24868845
TI  - Reporting patient safety indicator-15.

PMID- 24868846
TI  - Remembering Hank.

PMID- 24868848
TI  - Physicians play important role in on-site survey process.

PMID- 24868847
TI  - Patient quality of life: vitally important.

PMID- 24868849
TI  - NTDB data points: residential institutions.

PMID- 24868850
TI  - Activation of cell-mediated immunity by Morinda citrifolia fruit extract and its
      constituents.
AB  - Morinda citrifolia, commonly known as noni, is a traditional natural medicine in
      French Polynesia and Hawaii. Functional foods derived from M. citrifolia fruit
      have been marketed to help prevent diseases and promote good health. The
      objective of this study was to assess the effects of M. citrifolia fruit on cell
      mediated immunity. In the picryl chloride-induced contact dermatitis test, M.
      citrifolia fruit extract (Noni-ext) inhibited the suppression of cell-mediated
      immunity by immunosuppressive substances isolated from freeze-dried ascites of
      Ehrlich carcinoma-bearing mice (EC-sup). In addition, Noni-ext inhibited
      reduction of IL-2 production in EC-sup-treated mice and activated natural killer
      cells in normal mice. These results suggest that Noni-ext has multiple effects on
      the recovery of cell-mediated immunity. Furthermore, we investigated the active
      principles of Noni-ext and identified an iridoid glycoside, deacetylasperulosidic
      acid. Oral administration of deacetylasperulosidic acid inhibited the reduction
      of ear swelling, and also cancelled the suppression of IL-2 production along with
      the activation of natural killer cells in the same manner as that of Noni-ext.

PMID- 24868851
TI  - A new pyrrolosesquiterpene from the terrestrial Streptomyces sp. Hd7-21.

PMID- 24868852
TI  - Structure-activity relationships of tanshinones in activating Nrf2. A DFT study
      and implications for multifunctional antioxidant discovery.
AB  - A series of recent studies reveal that tanshinones, derived from the traditional
      Chinese herbal medicine Salvia miltiorrhiza Bunge, are promising multifunctional
      antioxidants by activating nuclear factor (erythroid-derived 2) - like 2 (Nrf2).
      It is thus of great interest to elucidate their structure-activity relationships
      (SAR) for Nrf2 activation. In this study, two theoretical parameters
      characterizing the electron-abstracting potential, namely, electron affinity (EA)
      and energy level of the lowest unoccupied molecular orbital (ELUMO), are
      calculated by a density functional theory (DFT) method. By these parameters, we
      provide a satisfactory explanation to the SAR oftanshinones for activating Nrf2,
      which is helpful to find new multifunctional antioxidants.

PMID- 24868853
TI  - Chemical modifications of cinchona alkaloids lead to enhanced inhibition of human
      butyrylcholinesterase.
AB  - Butyrylcholinesterase (BChE) inhibitors were identified from a collection
      containing cinchonine, cinchonidine and synthetic derivatives, and further
      characterized using cytotoxicity and molecular docking studies. The most active
      ones were: (10 triple bond)-10,11-dibromo-10,11-dihydrocinchonidine (11), a
      competitive inhibitor with Ki = 3.45 +/- 0.39 microM, and IC50 BChE = 9.83 +/-
      0.30 microM/human (h)BChE = 34.47 +/- 4.63 and O-(trimethylsilyl)cinchonine (15),
      a mixed inhibitor with Kiuc = 1.73 +/- 0.46 microM and Kic = 0.85 +/- 0.26
      microM, and IC50 BChE = 0.56 +/- 0.14 microM/hBChE = 0.24 +/- 0.04. In
      cytotoxicity experiments, > or = 80% of the cells remained viable when exposed to
      concentrations of up to 80 microM of both inhibitors in four different cell
      lines, including neurons. Due to the bulkier trimethylsilyl side group of 15, it
      covered the active site of hBChE better than 11 with an OH-group while not being
      able to fit into the active site gorge of hAChE, thus explaining the selectivity
      of 15 towards hBChE.

PMID- 24868854
TI  - Alkaloids from marine sponges as stimulators of initial stages of development of
      agricultural plants.
AB  - Damirone A (1), damirone B (2), makaluvamine G (3), debromohymenialdisine (4),
      and dibromoagelaspongin (5) were examined for their ability to stimulate growth
      of seedling roots of barley (Hordeum vulgare L.), buckwheat (Fagopyrum esculentum
      Moench), corn (Zea mays L.), soy (Glycine max (L.) Merr.}, and wheat (Triticum
      aestivum L.). It was shown that the stimulatory effects depend on the chemical
      structure of the alkaloids and on the plant species. Compounds 1, 3, and 4 are
      efficient for growth of seedling roots of barley, compounds 2-5, at different
      concentrations, stimulate growth of buckwheat roots, and compound 5 stimulates
      growth of wheat roots. These compounds can be recommended for field study as
      plant growth stimulators.

PMID- 24868855
TI  - Crinane alkaloids of the amaryllidaceae with cytotoxic effects in human cervical
      adenocarcinoma (HeLa) cells.
AB  - The family Amaryllidaceae has a long history of usage in the traditional
      medicinal practices of the indigenous peoples of South Africa, with three of its
      species known to be used for cancer treatment. Furthermore, the Amaryllidaceae is
      widely recognized for its unique alkaloid constituents, several of which exhibit
      potent and selective cytotoxic activities. In this study, several crinane
      alkaloids derived from local Amaryllidaceae species were examined for cytotoxic
      effects against the human cervical adenocarcinoma cell line, of which
      distichamine was the most potent (IC50 2.2 microM).

PMID- 24868856
TI  - Alkaloids from Xylariaceae sp., a marine-derived fungus.
AB  - A new pyridine derivative, 5-(2'-hydroxypropyl)pyridin-3-ol (1), with seven known
      alkaloids, 3-hydroxy-5-methyl-5,6-dihydro-7H-cyclopenta[b]pyridin-7-one (2),
      penicillenol A1 (3), penicillenol A2 (4), a mixture of quinolactacin AI (5a) and
      quinolactacin A2 (5b), and a mixture of quinolactacin C1 (6a) and quinolactacin
      C2 (6b), were isolated from the culture broth of a marine-derived fungus
      Xylariaceae sp. SCSGAF0086. Their structures were elucidated by spectroscopic
      methods. Compound 2 showed weak antimicrobial activity against Bacillus subtilis,
      and a mixture of 6a and 6b exhibited strong antifouling activity toward Bugula
      neritina larval settlement.

PMID- 24868858
TI  - Two new thyminenol derivatives from the marine sponge Haliclona sp.
AB  - Investigation of the marine sponge Haliclona sp. led to the isolation of two new
      thyminenol derivatives, named cis-thyminenol (1) and trans-thyminenol (2). The
      structures of the new isolates were elucidated on the basis of extensive
      spectroscopic analysis.

PMID- 24868857
TI  - Occurrence of a taurine derivative in an antarctic glass sponge.
AB  - The n-butanol extract of an Antarctic hexactinellid sponge, Anoxycalyx
      (Scolymastra) joubini, was found to contain a taurine-conjugated anthranilic
      acid, never reported so far either as a natural product or by synthesis. The
      compound was inactive against human cancer cells in an in vitro growth inhibitory
      test, and also showed no antibacterial activity.

PMID- 24868859
TI  - Decorosides A and B, cytotoxic flavonoid glycosides from the leaves of
      Rhododendron decorum.
AB  - Bioassay and NMR-guided fractionation of the methanolic extract of Rhododendron
      decorum leaves resulted in the isolation of two new flavonoid glycosides, 5,7
      dihydroxy-6,8-dimethyldihydroflavanone-7-O-alpha-L-arabinopyranosyl(1-->6)-beta-D
      glucopyranoside (decoroside A, 1) and its 3-hydroxy congener (decoroside B, 2),
      along with five known compounds myricitrin (3), afzelin (4), (-)-epicatechin (5),
      (+)-catechin (6), and ampeloptin (7). The structures of the isolated compounds
      were elucidated by extensive interpretation of their spectral data. Biological
      evaluation using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
      (MTT) assay revealed promising cytotoxic activities of these compounds against
      different cancer cell lines.

PMID- 24868861
TI  - In vitro antioxidant activity and phenolic content of Cedrus brevifolia bark.
AB  - A raw extract and four extractive fractions were obtained from Cedrus brevifolia
      (Cyprus cedar) bark. They were all studied regarding the phenolic content and
      profile using spectrophotometry and HPLC-DAD-ESI-MS. The antioxidant activity was
      investigated using in vitro assays: DPPH and ABTS radicals scavenging and
      reducing power assays. The ethyl acetate fraction had the highest total phenolic
      and proanthocyanidin contents; a taxifolin-O-hexoside, catechin, epicatechin and
      procyanidin oligomers (three dimers, two trimers) were identified in this
      fraction. The ethyl acetate fraction was found to possess the highest DPPH and
      ABTS radicals scavenging effects (EC50 = 13.9 +/- 0.3 and 2.3 +/- 0.0 microg/mL,
      respectively) and reducing capacity (EC50 = 9.1 +/- 0.1 microg/mL). Antioxidant
      effects were highly correlated with total phenolic and proanthocyanidin contents
      (r = 0.89-0.99). These results suggest that Cedrus brevifolia bark is a new
      source of antioxidants.

PMID- 24868860
TI  - In vitro cultures of Bituminaria bituminosa: pterocarpan, furanocoumarin and
      isoflavone production and cytotoxic activity evaluation.
AB  - Bituminaria bituminosa L. is known for producing several compounds with
      considerable pharmaceutical interest, such as phenylpropanoids, furanocoumarins
      and pterocarpans. In vitro cultures of seedlings, shoots, and callus have been
      produced to obtain plant materials useful for the production of these
      metabolites. The secondary metabolite profile was evaluated by HPLC-DAD. The
      extracts of all the in vitro material contained the flavonoid daidzein, while
      plicatin B, erybraedin C and bitucarpin A were found only in the extracts of the
      in vitro shoots and in wild shoots. The furanocoumarins angelicin and psoralen
      were found in in vivo and in vitro plants, but in the callus were not detectable.
      The extracts were also tested for cytotoxic activity in HeLa cell culture; the
      highest level of cytotoxicity was found in in vitro shoot extracts.

PMID- 24868863
TI  - A new coumarin and cytotoxic activities of constituents from Cinnamomum cassia.
AB  - A new coumarin derivative, coumacasia (1) and eight known compounds, coumarin
      (2), cinnamaldehyde (3), 2-methoxycinnamaldehyde (4), 2-hydroxycinnamaldehyde
      (5), coniferaldehyde (6), cinnamic acid (7), 2-hydroxycinnamic acid (8), and
      cinnamic alcohol (9), were isolated from the methanol extract of Cinnamomum
      cassia. Their structures were elucidated by spectral data and by comparison with
      the reported literature. The cytotoxic activities of compounds 1-9 were evaluated
      with two human cancer cell lines, HL-60 and A-549. Compound 1 showed growth
      inhibitory effects in the HL-60 and A-549 cell lines with IC50 values of 8.2 +/-
      0.5 and 11.3 +/- 1.1 microM, respectively. Compounds 3-6, and 8 exhibited
      moderate cytotoxicity with IC50 values ranging from 20.5 to 65.6 microM.

PMID- 24868862
TI  - Evaluation of bioactive components and antioxidant and anticancer properties of
      citrus wastes generated during bioethanol production.
AB  - In the bioethanol production process employing citrus peels, a large amount of
      enzymatic hydrolyzed residues is generated as waste material. The bioactive
      compounds, and antioxidant and anticancer activities of these residues were
      investigated in the present study. Hydrolyzed citrus residues exhibited similar
      antioxidant activity as the unhydrolyzed control, which was positively correlated
      to the contents of total phenols, flavonoids and total carotenoid. Some
      flavonoids (naringin, naringenin, hesperetin and neohesperidin) and two high
      value co-products (D-limonene and galacturonic acid) were detected only in
      hydrolyzed residues. In addition, hydrolyzed residues showed antiproliferative
      activity and sub-G1 arrest in human melanoma A375 and colon cancer HCT116 cells.
      These results provide an alternative use for hydrolyzed citrus residues in the
      functional food, cosmetic and pharmaceutical industries.

PMID- 24868864
TI  - Coumarin compounds in Coronilla scorpioides callus cultures.
AB  - Coronilla scorpioides (L.) W.D.J. Koch is known for producing several compounds
      with pharmaceutical interest, such as the hydroxycoumarins umbelliferone,
      scopoletin and daphnoretin, the dihydrofuranocoumarin marmesin, and the
      furocoumarin psoralen. In vitro callus cultures of C. scorpioides were
      established from hypocotyl, leaf, stem internode and root explants in order to
      evaluate the possibility of in vitro production of these active secondary
      metabolites. Calli were obtained with high frequency from all the explant types
      both in B5 and MS medium. However, after the third subculture, B5 medium, giving
      the best results, was selected for subsequent transfers. Homogeneous calli were
      kept either in darkness or in light. Chemical analyses showed that scopoletin and
      the intermediate products of the biogenetic pathway of psoralen, umbelliferone
      and marmesin, were always present in the calli and excreted into the media, while
      daphnoretin was never detected. Light seems to be a prerequisite for psoralen
      biosynthesis. Root-derived calli produced a significantly higher amount of
      psoralen (137.5 microg g(-1) DW). Principal component analysis showed that
      umbelliferone, marmesin and psoralen contents are related to variables associated
      with different explant types.

PMID- 24868865
TI  - A new isocoumarin from Cajanus cajan (Fabaceae).
AB  - A new isocoumarin, 3-phenyl-8-hydroxy-6-methoxy-5-gamma,gamma-dimethylallyl
      isocoumarin, named cajavilmina (1) and eight known compounds: a-amirenone (2),
      beta-amirenone (3), lupenone (4), 5-hydroxy-7-methoxydihydroflavone (5),
      longistilin C (6), 3-hydroxy-5-methoxystilbene (7), beta-sitosterol (8) and
      stigmasterol (9) were identified in a dichloromethane fraction from Cajanus cajan
      leaves. Structures were elucidated by analysis of spectral data, mainly those
      afforded by 1H, NOEDIFF and 13C NMR (1D and 2D NMR HMQC, HMBC and COSY) and mass
      spectra.

PMID- 24868866
TI  - Styryllactones and acetogenins from the fruits of Goniothalamus macrocalyx.
AB  - Two new styryllactones, macrocalactone (1) and 3-deoxycardiobutanolide (2), were
      isolated from the fruits of Goniothalamus macrocalyx Ban (Annonaceae), together
      with seven known compounds including four acetogenins, annonacin (3), solamin
      (4), isoannonacin (5), trans-murisolinone (6), and three other compounds, 7
      acetylaltholactone (7), beta-caryophyllene-8R,9R-oxide (8) and 2-(2'
      hydroxytetracosanoylamino)-octadecane-1,3,4-triol (9). Their structures were
      determined by spectroscopic and MS analysis. The absolute configuration of 1 was
      determined by X-ray crystallographic analysis. The structures of the acetogenins
      were confirmed by liquid chromatography coupled to a hybrid quadrupole-time of
      flight mass spectrometer, using post-column lithium infusion. The results were
      compared with the fragmentation obtained with a hybrid linear trap-orbitrap mass
      spectrometer. Compound 7 had cytotoxicity against KB, HepG2, Lu, and MCF7 cell
      lines with IC50 values of 13.1, 23.7, 26.3 and 60.2 microM, respectively, whereas
      annonacin (3) was selectively active against KB cells (IC50 value of 6.5 microM).
      The discovery of 3-deoxycardiobutanolide (2) from the fruits of this plant
      revealed that G. macrocalyx could be a valuable natural resource to obtain this
      compound as it has been previously reported to have a significant cytotoxicity
      against different cancer cell lines, especially HL-60 cells.

PMID- 24868867
TI  - Potent acetylcholinesterase inhibitory compounds from Myristica fragrans.
AB  - The anti-cholinesterase activity was evaluated of the ethyl acetate fraction of
      the methanol extract of Myristica fragrans Houtt (Myristicaceae) seeds and of
      compounds isolated from it by various chromatographic techniques. The chemical
      structures of the compounds were determined from spectroscopic analyses (NMR
      data). Thirteen compounds (1-13) were isolated and identified. Compound 8 { [(7S)
      8'-(4'-hydroxy-3'-methoxyphenyl)-7-hydroxypropyl]benzene-2,4-diol) showed the
      most effective activity with an IC50 value of 35.1 microM, followed by compounds
      2 [(8R,8'S)-7'-(3',4'-methylenedioxyphenyl)-8,8'-dimethyl-7-(3,4-dihydroxyphenyl)
      butane] and 11 (malabaricone C) with IC50 values of 42.1 and 44.0 pM,
      respectively. This is the first report of significant anticholinesterase
      properties of M. fragrans seeds. The findings demonstrate that M. fragrans could
      be used beneficially in the treatment of Alzheimer's disease.

PMID- 24868868
TI  - Clastogenic effect of atranorin, evernic acid, and usnic acid on human
      lymphocytes.
AB  - Three lichen secondary metabolites atranorin (1), evernic acid (2), and usnic
      acid (3), were evaluated for their in vitro clastogenic and antiproliferative
      effects on human lymphocytes using the cytochalasin-B blocked micronucleus (CBMN)
      assay at concentrations of 2 microg/mL, 4 microg/mL and 6 microg/mL of final
      culture solution. The frequency of micronucleus (MN) was scored in binucleated
      cells, and cytokinesis-block proliferation index (CBPI) was calculated. Among the
      tested compounds, 3 exhibited the most prominent effect decreasing the frequency
      of MN in the range of 42.5% - 48.9%, that is about double of the positive control
      amifostin WR-2721 that reduces MN frequency for 22.0%. The effect of evernic acid
      was approximately equal to action of amifostin (23.2% -32.9%). Atranorin at
      concentrations of 2 microg/mL and 4 microg/mL decreasing the frequency of MN only
      for 11.1% and 1.8%, while in concentration of 6 microg/mL increases the frequency
      of MN for 9.6 %. The comparable CBPI values of the investigated compounds and
      control suggested that they did not show a statistically significant inhibitory
      effect on lymphocyte cell proliferation at applied concentrations.

PMID- 24868869
TI  - MAO-A inhibition profiles of some benzophenone glucosides from Gentiana verna
      subsp. pontica.
AB  - Gentiana verna L. subsp. pontica (Soltok.) Hayek, G. pyrenaica L., and G. verna
      L. subsp. balcanica Pritchard from Turkey were tested for their MAO-A inhibitory
      effects. A photometric peroxidase linked MAO-A bioassay performed on the H20
      extracts prepared from the methanolic extracts of the title plants revealed the
      potential effect of G. verna subsp. pontica and three benzophenone glucosides;
      2,3'-dihydroxy-4-methoxy-benzophenone-6-O-beta-glucopyranoside (1), 2,4,3',4'
      tetrahydroxy-benzophenone-6-O-beta-glucopyranoside (maclurin-6-O-f
      glucopyranoside) (2) and 2,4,3'-trihydroxy-benzophenone-6-O-beta-glucopyranoside
      (3) isolated from G. verna subsp. pontica. Among the benzophenone glucosides 1
      and 2 exhibited significant inhibition of MAO-A (IC50 = 31.3 +/- 4 microM and 41
      +/- 4.7 microM resp.).

PMID- 24868870
TI  - Phytochemical investigations of Lonchocarpus bark extracts from Monteverde, Costa
      Rica.
AB  - The acetone bark extracts of three species of Lonchocarpus from Monteverde, Costa
      Rica, L. atropurpureus, L. oliganthus, and L. monteviridis, were screened for
      antibacterial, cytotoxic, and antioxidant activities. L. orotinus extract was
      antibacterial against Bacillus cereus (MIC = 39 microg/mL), while L. monteviridis
      exhibited the most antioxidant activity. None of the Lonchocarpus extracts showed
      cytotoxic activity against MCF-7 cells. Fatty acids and atraric acid were
      isolated and purified from L. atropurpureus bark, fatty acids and loliolide from
      L. oliganthus bark, and leonuriside A and beta-D-glucopyranos-1-yl N
      methylpyrrole-2-carboxylate from L. monteviridis bark. Atraric acid showed
      cytotoxic and antimicrobial activities.

PMID- 24868871
TI  - Immune enhancing effects of Echinacea purpurea root extract by reducing
      regulatory T cell number and function.
AB  - Echinacea purpurea preparations (EPs) have been traditionally used for the
      treatment of various infections and also for wound healing. Accumulating evidence
      suggests their immunostimulatory effects. Regulatory T cells (Tregs) are known to
      play a key role in immune regulation in vivo. However, there have been no reports
      so far on the effects of EP on the frequency or function of Tregs in vivo.
      Therefore, in the present study, we investigated the quantitative and functional
      changes in Tregs by in vivo administration with EP. The frequencies of CD4+FoxP3+
      and CD4+CD25+ Tregs in the spleens of BALB/c mice administered with EP for 3
      weeks were investigated by flow cytometry. The suppressive function of CD4CD25+
      Tregs in association with the proliferative activity of CD4+CD25 effector T cells
      (Teffs) and the feeder function of CD4 antigen-presenting cells (APCs) were
      analyzed by carboxyfluorescein succinimidyl ester-dilution assay. The results
      showed a lowered frequency of CD4+FoxP3+ and CD4+CD25+ Tregs and attenuated
      suppressive function of CD4+CD25+ Tregs, while the feeder function of APCs was
      enhanced in the EP-administered mice. On the other hand, the proliferative
      activity of Teffs was not significantly different in the EP-administered mice.
      The results suggest that decreased number and function of Tregs, in association
      with the enhanced feeder function of APCs, may contribute to the enhancement of
      immune function by EP.

PMID- 24868872
TI  - Isocorilagin, a cholinesterase inhibitor from Phyllanthus niruri.
AB  - Drugs that have dual inhibition of acetylcholinesterase (AChE) and
      butyrylcholinesterase (BChE) produce better clinical efficacy against Alzheimer's
      disease (AD) than those that selectively inhibit one enzyme. A dual
      cholinesterase inhibitory-guided fractionation of Phyllanthus niruri leaves
      afforded isocorilagin, a bioactive tannin possessing good inhibitory activities
      against AChE (IC50: 0.49 microM) and BChE (IC50: 4.20 microM). Interestingly,
      isocorilagin was relatively 2- to 3-fold more potent than galanthamine, the
      clinically used inhibitor. The kinetic analyses suggested that isocorilagin was a
      non-competitive inhibitor for AChE and an uncompetitive inhibitor for BChE, with
      calculated Ki values of 1.49 microM and 2.86 microM, respectively. In silico
      molecular docking revealed that isocorilagin effectively blocked the substrate
      entry by forming hydrogen bonding with residues at the entrance of the AChE
      active site. With BChE, the compound completely docked inside and occupied the
      active site of the enzyme. This study demonstrated for the first time the potent
      cholinesterase inhibitory activities of isocorilagin, a promising lead that is
      worthy of further investigation.

PMID- 24868873
TI  - Antioxidant activity and phenolic content of Bergenia crassifolia, B. x ornata
      and B. ciliata.
AB  - This study focused on a phytochemical analysis of Bergenia crassifolia (L.)
      Fritsch., B. ciliata (Haw.) Sternb., and B. x ornata Stein. and evaluation of
      their free radical scavenging properties. Arbutin and total tannin contents of
      the leaves of the Bergenia species were determined during different seasons. The
      present study also aimed at analyzing, for the first time, environmental
      influence on concentrations of phenolic metabolites in Bergenia leaves. The
      highest total tannin content was found in the leaves of B. crassifolia (24.9-48.7
      mg x g(-1) DW) and B. x ornata (36.9 mg.g(-1) DW). The highest amount of arbutin
      was in the leaves of B. x ornata (35.8-51.0 mg.g(-1) DW) and B. crassifolia (24.6
      41.7 mg x g(-1) DW). Autumn was better than spring for the collection of Bergenia
      leaves for the highest amount of arbutin (B. x ornata: 51.0 mg x g(-1) DW). Free
      radical scavenging potential, in DPPH and ABTS assays, of the water leaf extracts
      revealed that extracts of B. crassifolia and B. x ornata are the most active
      radical scavengers. Antioxidant activity correlated well with the content of
      total tannin, especially in the ABTS assay, which suggests an important role for
      these compounds in antioxidant activity. It was shown that phenolic
      concentrations in Bergenia leaves are affected by seasonal factors. A significant
      correlation was found between arbutin and tannin contents and the average
      humidity.

PMID- 24868874
TI  - Antioxidant activity and total phenolic contents of three Bupleurum taxa.
AB  - Bupleuri Radix (Bupleurum spp. root) is one of the most important crude drugs in
      Korea, China and Japan. We investigated the total phenolic content and
      antioxidant activity of three Bupleurum taxa (B. falcatum, B. falcatum 'Mishima'
      and B. latissimum). The highest total phenolic content was found in B. latissimum
      (18.6 +/- 1.7 mg/g) and the least in B. falcatum 'Mishima' (9.4 +/- 0.5 mg/g).
      The ethyl acetate fractions obtained from B. falcatum and B. falcatum 'Mishima'
      showed higher DPPH radical scavenging activity than the other fractions. In the
      case of B. latissimum, the DPPH radical scavenging activity of the diethyl ether
      fraction was higher than that of the other fractions. These results suggest that
      the three Bupleurum plants may be used as a food additive as a natural
      antioxidant.

PMID- 24868875
TI  - Quantification of gamma-aminobutyric acid in Sri Lankan tea by means of ultra
      performance tandem mass spectrometry.
AB  - Gamma-Aminobutyric acid (GABA), an important bioactive component of tea, acts as
      a major inhibitory neurotransmitter and is considered to influence other
      physiological processes in human as well as in planta. In the hereby presented
      study, the content of this valuable metabolite was investigated in two novel
      types of Ceylon Tea, explicitly "Silver Tips" and "White Tea", originating from
      minimally processed buds of the unique cultivar, "TRI 2043". The samples were
      subjected to hot water infusion, equivalent to the traditional beverage
      preparation procedure, and analyzed by means of hydrophilic interaction ultra
      performance liquid chromatography coupled to tandem mass spectrometry (HILIC LC
      MS/MS). The registered GABA levels were compared with those obtained for the
      classic "Black Tea" and "Green Tea" samples from Sri Lanka. A high variation of
      GABA content was observed among the different tea types, especially in the case
      of "Silver Tips" and "White Tea", indicating the crucial influence of the
      manufacturing procedure (processing extent) on the final abundance of the
      bioactive component of interest. Furthermore, "White Tea" samples boasted the
      highest GABA concentration reported for this type of tea so far, reaching up to
      50% of that characteristic of the high-priced "GABA Tea". Therefore, "White Tea"
      and "Silver Tips" were proved to be high quality tea with amounts of gamma
      aminobutyric acid comparable with those described for similar types before. To
      our knowledge, this is the first report on HILIC LC-MS/MS application for the
      quantification of GABA and for in-depth characterization of teas from Sri Lanka.

PMID- 24868876
TI  - 5-(Hydroxymethyl)-2-furaldehyde inhibits adipogenic and enhances osteogenic
      differentiation of rat bone mesenchymal stem cells.
AB  - Eucommiae Cortex (Eucommia ulmoides Oliver Bark) has been used for anti
      osteoporosis usually as an ethnic drug for hundred years in China. In this study,
      a bioactive compound, 5-(hydroxymethyl)-2-furaldehyde (5-HMF), was isolated from
      Eucommiae Cortex. We found that after rat bone mesenchymal stem cells (bMSCs)
      were induced by 5-HMF at the concentration of 0.05, 0.10 and 0.20 microg/mL in
      the normal medium for 7 and 14 days, the mRNA expression of ALP, COL1alpha1 (7
      days only), OCN and OPN increased. However, in the adipogenic induction medium
      (AIM), the mRNA expression of PPARgamma, FABP4, C/EBPalpha and LPL decreased with
      the 5-HMF treatment. Mineralized nodule formations were enhanced after bMSCs were
      induced by 5-HMF for 14 and 21 days in normal medium. In the AIM medium, 5-HMF
      not only inhibited the formation of adipose cells obviously, but also stimulated
      the mineralized nodule formation after induced for 21 days. These results
      indicated that 5-HMF was a powerful inhibitor of adipogenesis and enhancer of
      osteoblastogenesis. It may be one of the constituents contributing to anti
      osteoporosis in Eucommiae Cortex.

PMID- 24868877
TI  - Variation of glucosinolate accumulation and gene expression of transcription
      factors at different stages of Chinese cabbage seedlings under light and dark
      conditions.
AB  - Chinese cabbage is one of the most important leafy vegetables widely used in East
      Asian cuisines. The glucosinolate (GSL) accumulation and transcript levels of 7
      transcription factors (Dof1.1, IQD1-1, MYB28, MYB29, MYB34, MYB51, and MYB122,
      and their isoforms) involved in the biosynthesis of aliphatic and indolic
      glucosinolates (GSLs) were analyzed at different stages of Chinese cabbage
      (Brassica rapa ssp. pekinensis) seedlings under light and dark conditions using
      high performance liquid chromatography and quantitative real time PCR. During
      seedling development, transcription of almost all transcription factors under
      light conditions was higher expressed than under dark conditions. Five aliphatic
      GSLs (progoitrin, sinigrin, glucoalyssin, gluconapin, and glucobrassicanapin) and
      four indolic GSLs (4-hydroxyglucobrassicin, glucobrassicin, 4
      methoxyglucobrassicin, and neoglucobrasscin) were detected. Total GSL contents
      under light conditions 6, 8, and 10 days after sowing (DAS) were 3.2-, 3.9-, and
      6.9-fold higher, respectively than those of dark conditions. Interestingly, total
      GSL contents 2 {85.4 micromol/g dry weight (DW)} to 10 (7.74 micromol/g DW) DAS
      under dark conditions were gradually decreased. In this study, our results
      suggest that light affects the levels of GSL in Chinese cabbage seedlings. These
      results could be useful for obtaining cabbage varieties rich in GSLs.

PMID- 24868878
TI  - Identification of the hydroxamate siderophore ferricrocin in Cladosporium
      cladosporioides.
AB  - The hydroxamate siderophore ferricrocin was identified in Cladosporium
      cladosporioides growth medium by solid phase extraction and ultra high pressure
      liquid chromatography coupled to a time of flight mass spectrometer (UHPLC/QTOF
      MS). Both desferricrocin and ferricrocin were detected in the extracellular
      medium assisted by high resolution mass spectrometry. This is the first
      identification of a hydroxamate siderophore in Cladosporium cladosporioides. This
      finding emphasizes the common meaning of ferricrocin in fungi.

PMID- 24868879
TI  - Structure characterization and adhesive ability of a polysaccharide from tendrils
      of Parthenocissus heterophylla.
AB  - In order to reveal the structure of the polysaccharide and its contribution to
      the biological adhesion system of Parthenocissus heterophylla, a water-soluble
      polysaccharide (PT-A) was isolated from tendrils using DEAE-cellulose and
      Sephadex G-100 columns. PT-A mainly consisted of a backbone of (1-->3)-linked
      beta-D-Galp residues and substituted at 0-6 with side chains of (1-->5)-linked
      alpha-L-Araf residues and glucomannopyranosyl residues. Individual polysaccharide
      chains of PT-A with the approximately height of 0.75 nm were observed by AFM. The
      analysis of force curves indicated that PT-A was a kind of elastic polysaccharide
      with a maximum adhesion force of 279.98 nN, which could be applied as a potential
      bio-adhesive.

PMID- 24868880
TI  - Two peptides, cycloaspeptide A and nazumamide A from a sponge associated marine
      actinobacterium Salinispora sp.
AB  - Marine sponges are a major component of benthic communities and act as a
      reservoir for microbial species. In terms of biomass, they are the richest source
      of secondary metabolite production, with the potential to influence both benthic
      and pelagic systems. In most cases it is the sponge-associated microbes that
      account for many of the secondary metabolites assigned to the host. Here we
      report the occurrence of cycloaspeptide A, a fungus-derived cyclic peptide, in a
      culturable bacterium Salinispora arenicola. We have also identified nazumamide A,
      a sponge-derived linear tetrapeptide currently used as a thrombin inhibitor, in
      Salinispora pacifica. Their structures were determined using an integrated
      approach consisting of: (1) HPLC-UV-Vis-QToF-MS analysis with multimode
      ionization (ESI and APCI) and fast polarity switching; (2) database searching and
      matching of monoisotopic masses, retention times, mass spectra of the precursor
      and product ions of the compounds of interest and the authentic reference
      standards thereof.

PMID- 24868881
TI  - Full assignments of the 1H, 13C and 15N magnetic resonance spectra of two
      porphyrin compounds.
AB  - Two chlorin derivatives, rhodochlorin dimethyl ester (7) and chlorin-e6 trimethyl
      ester (8), were prepared from methyl pheophobide a (6) through base-degradation
      of the E ring and methylation of the carboxylic acids. Full assignments of the
      1H, 13C and 15N magnetic resonance spectra of compounds 7 and 8 were made by 2D
      NMR techniques (1H-1H COSY, 1H-13C HMQC, 1H-13C HMBC, 1H-15N HMBC).

PMID- 24868882
TI  - The effects of Salacia reticulata on anti-cellular oxidants and melanogenesis
      inhibition in alpha-MSH-stimulated and UV irradiated B16 melanoma cells.
AB  - The purposes of this study were to investigate the inhibitory effects of Salacia
      reticulata Tul. root extract on cellular oxidants and melanogenesis in B16
      melanoma cells. Cells treated with non-toxic doses of S. reticulata root extract
      were investigated for their effects on melanogenesis, cellular tyrosinase
      activity and cellular oxidant scavenging activity. The results indicated that S.
      reticulata extract inhibited melanin synthesis and tyrosinase activity in alpha
      MSH-induced or UV-irradiated B16 melanoma cells in a dose dependent manner.
      Additionally, the extract also exhibited anti-cellular oxidants in UV-induced
      radical melanoma cells. Altogether, these results suggested that S. reticulata
      root extract has roles in suppression of melanogenesis and oxidant inhibition. S.
      reticulata root extract may be a potential source for the development of
      pharmaceutical products for treatment of skin hyperpigmentation disorders.

PMID- 24868883
TI  - Korean propolis suppresses angiogenesis through inhibition of tube formation and
      endothelial cell proliferation.
AB  - Propolis, a sticky material that honeybees collect from living plants, has been
      used for its pharmaceutical properties since ancient times. In this study, we
      examined the effects of ethanol extracts of Korean propolis (EEKP) from various
      geographic regions on the inhibition of angiogenesis, both in vitro and in vivo.
      The effects of EEKP were tested on in vitro models of angiogenesis, that is, tube
      formation and proliferation of human umbilical vein endothelial cells (HUVECs).
      All EEKP samples exhibited significant inhibitory effects on tube formation of
      HUVECs in a concentration-dependent manner (6.25-25 microg/mL). In addition, two
      EEKP samples, prepared from Uijeongbu and Pyoseon propolis, significantly
      suppressed the proliferation of HUVECs in a concentration-dependent manner (3.13
      25 microg/mL). Furthermore, in an in vivo angiogenesis assay using the chick
      embryo chorioallantoic membrane (CAM) system, we found that the two EEKP samples
      significantly reduced the number of newly formed vessels. These results indicate
      that Korean propolis may have potential applications in the prevention and
      treatment of angiogenesis-related diseases such as cancer.

PMID- 24868884
TI  - ETAS, an enzyme-treated asparagus extract, attenuates amyloid beta-induced
      cellular disorder in PC12 cells.
AB  - One of the pathological characterizations of Alzheimer's disease (AD) is the
      deposition of amyloid beta peptide (Abeta) in cerebral cortical cells. The
      deposition of Abeta in neuronal cells leads to an increase in the production of
      free radicals that are typified by reactive oxygen species (ROS), thereby
      inducing cell death. A growing body of evidence now suggests that several plant
      derived food ingredients are capable of scavenging ROS in mammalian cells. The
      purpose of the present study was to investigate whether enzyme-treated asparagus
      extract (ETAS), which is rich in antioxidants, is one of these ingredients. The
      pre-incubation of differentiated PC 12 cells with ETAS significantly recovered
      Abeta-induced reduction of cell viability, which was accompanied by reduced
      levels of ROS. These results suggest that ETAS may be one of the functional food
      ingredients with anti-oxidative capacity to help prevent AD.

PMID- 24868885
TI  - An integrated approach to the evaluation of a metabolomic fingerprint for a
      phytocomplex. Focus on artichoke [Cynara cardunculus subsp. scolymus] leaf.
AB  - The availability of reliable herbal formulations is essential in order to assure
      the maximal activity and to limit unwanted side-effects. The correct
      concentration of declared components of herbal products is a matter of health
      legislation and regulation, but is still a topic under debate in the field of
      quality control assessment. In the present work specific constituents of
      artichoke leaf extracts, considered as a test herbal product, were measured by
      standard spectrophotometric and HPLC methods (for quantitative determination of
      some components only), and results were correlated with the ESI-MS (showing the
      full metabolomic fingerprint). Phytocomplex stability over time was also
      investigated in batches submitted to different storage conditions. The results
      indicated excellent agreement between the two approaches in the measurement of
      total caffeoylquinic acids and chlorogenic acid contents, but the metabolomic ESI
      MS method approach provides a more complete evaluation and monitoring of the
      composition of a herbal product, without focusing only on a single/few compound
      measurements. Therefore, the ESI-MS method can be proposed for the evaluation of
      the quality of complex matrices, such as those in a phytocomplex. Another aspect
      lies in the possibility to obtain a broad-spectrum stability control of herbal
      formulations, requiring minimal sample pre-processing procedures.

PMID- 24868886
TI  - Cytotoxicity and antimicrobial activity of the essential oil from Satureja
      montana subsp. pisidica (Lamiceae).
AB  - The antimicrobial and cytotoxic activities of the essential oil of Satureja
      montana ssp. pisidica from two localities (mountains Korab and Galicica) were
      studied. Forty-nine components were identified in the each sample. Oxygenated
      monoterpene hydrocarbons were the major compounds: carvacrol, thymol, carvacrol
      methyl ether and beta-linalool. Both tested essential oils showed very high and
      similar antimicrobial activity. Minimal inhibitory concentrations ranged from
      12.5 microg/mL against S. epidermidis to 50 microg/mL against P. aeruginosa and
      C. albicans. The cytotoxic effect of the essential oils was tested against MDA-MB
      361, MDA-MB-453, HeLa, LS174 and MRC5 cells. The essential oil from Korab
      demonstrated significantly better results than the oil from Galicica,
      particularly against HeLa and MDA-MB-453 cell lines, with IC50 values of 63.5 and
      72.3 microg/mL, while the oil from Galicica was the most active on the human
      epithelial cervical cancer HeLa cells (IC50 99.7 microg/mL).

PMID- 24868887
TI  - Chemical composition of essential oils of Grindelia squarrosa and G. hirsutula.
AB  - The essential oils of Grindelia squarrosa (Pursh) Dunal and G. hirsutula Hook. &
      Am. cultivated in Romania were isolated by hydrodistillation. The essential oils
      were analyzed by a combination of GC-FID and GC-MS. The identification of the
      constituents was achieved from their retention indices and comparison of their MS
      data with computer library database and literature data. The fifty-six identified
      constituents accounted for 72.1-81.3% of the oils. The oils were found to contain
      a-pinene, beta-pinene, limonene, borneol, bornyl acetate and germacrene D as main
      constituents. The oils obtained from the two species showed small differences in
      chemical composition. However, menthol, menthone and pulegone were detected only
      in the essential oil of G. hirsutula.

PMID- 24868888
TI  - Seasonal influence on the essential oil of Eucalyptus microcorys.
AB  - The chemical composition of the essential oil, phenolic contents, and foliar
      nutrients of Eucalyptus microcorys leaves, cultivated in Brazil, was analysed on
      a monthly basis for one year. Canonical redundancy analysis correlated results
      with climate conditions (rainfall, humidity, and mean temperature), allowing
      three groups to be distinguished as regards temperature, flavonoids, and the
      content of some metals. Strong correlations between Mn, Cu, Zn, Ca, P, and K with
      some monoterpenes and phenolic compounds were observed. Oxygenated monoterpenes
      were predominant in all sampling months. Oil chemovariation may be influenced by
      climatic factors as well as by foliar nutrient variation.

PMID- 24868889
TI  - Composition of the essential oil of wild grown caraway in meadows of the Vienna
      region (Austria).
AB  - The essential oil compositions of the different plant parts of wild growing
      caraway (Carum carvi, Apiaceae) were analyzed by GC/MS and GC/FID. The plants
      came from two meadows in the Vienna region, Austria. The oils from young fruits
      had a high proportion of limonene (61-83%), and those from inflorescences
      limonene (39-62%) and germacrene D (23-41%). The carvone contents of fruits,
      inflorescences and leaves varied greatly. Leaves and stems, low in volatiles,
      were dominated by germacrene D and germacrene A. Therefore, wild caraway appears
      as a valuable aromatic herb in meadows.

PMID- 24868890
TI  - Volatile compounds from roots, stems and leaves of Angelica acutiloba growing in
      Taiwan.
AB  - The present study analyzed and compared the volatile compounds in fresh Angelica
      acutiloba roots, stems and leaves both qualitatively and quantitatively. The
      volatile compounds were isolated by either steam distillation (SD) or headspace
      solid phase microextraction (HS-SPME). A total of 61 compounds were identified
      using gas chromatography/mass spectrometry (GC/MS). All 61 compounds were
      verified by SD, with 3n-butyl phthalide, gamma-terpinene, p-cymene and cis-beta
      ocimene as the main compounds. Thirty-three compounds were verified by HS-SPME,
      with gamma-terpinene and p-cymene as the main compounds. The leaf samples
      contained the highest essential oil content. Compared with SD, HS-SPME sampling
      resulted in relatively higher amounts of highly volatile monoterpenes and lower
      amounts of less volatile compounds such as 3n-butyl phthalide. These findings
      demonstrate that A. acutiloba roots, stems and leaves have high 3n-butyl
      phthalide contents; thus, all parts of A. acutiloba may be used for further
      application and development.

PMID- 24868891
TI  - Anti-oxidant, anti-inflammatory and anti-proliferative activities of Moroccan
      commercial essential oils.
AB  - Essential oils (EO) possess antimicrobial, anti-inflammatory, insect repellent,
      anti-cancer, and antioxidant properties, among others. In the present work, the
      antioxidant, anti-inflammatory and anti-proliferative activities of Moroccan
      commercial EOs (Citrus aurantium, C. limon, Cupressus sempervirens, Eucalyptus
      globulus, Foeniculum vulgare and Thymus vulgaris) were evaluated and compared
      with their main constituents. T. vulgaris EO showed the best free radicals
      scavenging capacity. This EO was also the most effective against lipid
      peroxidation along with C. limon and F. vulgare EOs. C. sempervirens EO was the
      most effective in scavenging NO free radicals, whereas C. limon EO showed the
      best chelating power. Not all of the major compounds of the EO were responsible
      for the whole activity of the EOs. T. vulgaris EO showed the best anti
      proliferative activity against THP-1 cells in contrast to that of F. vulgare. The
      antioxidant and anti-inflammatory activities of the EOs were plant species
      dependent and not always attributable to the EOs main components. Nevertheless,
      the EOs anti-proliferative activities were more related to their main components,
      as with T. vulgaris, C. limon, E. globulus and C. sempervirens.

PMID- 24868892
TI  - [How to safely and effectively administer aminoglycoside antibiotics].
AB  - Aminoglycoside antibiotics (AA) are drugs with a narrow therapeutic window and
      cause severe and often irreversible side effects. They are often used in
      combination with other antibiotics to treat serious infections caused by aerobic
      Gram-negative rods. Irreversibly combined with rRNA (16S) subunit of the
      bacterial 30S ribosomal aminoacyl acceptor site interaction disrupting codon
      (mRNA) of the anticodon (in tRNA). For the bactericidal effect of AA correspond
      mainly oxygen free radicals, the concentration of drug in serum and post
      antibiotic effect. Studies show that the C max./MIC > 8-12 are associated with
      higher efficacy. AA can be served in the traditional manner or consolidated. In
      the course of treatment is necessary to monitor drug concentrations (C max, C
      min). A limitation in the use of AA is the othotoxicity and nephrotoxicity.
      Despite the limitations of AA remain a significant group of antibacterial agents.

PMID- 24868893
TI  - [Genetic predisposition to ischemic heart disease in patients with obstructive
      sleep apnea syndrome (OSAS)].
AB  - The incidence of ischemic heart disease (IHD) in patients with OSAS is estimated
      at around 20%. This greatly affect a common risk factors for both diseases: male
      gender, obesity, age and diabetes and hypertension. Attention is drawn to the
      possibility of genetic determinants of IHD. The aim of study was to answer the
      question whether the presence of polymorphisms of selected genes possibly related
      to IHD may be useful to isolate the group of patients with OSAS, especially
      vulnerable as a complication of IHD. Materials and methods. The study included
      600 people with OSAS, which was isolated in patients with IHD (127 people). The
      remaining 473 individuals were observed as a control group. The polymorphism of
      three genes were evaluated to find possible influence on the occurrence of IHD or
      myocardial infarction as follows: SREBF1 (sterol regulatory element binding
      transcription factor 1), REBF2 (sterol regulatory element binding transcription
      factor 2) and HIF1 (hypoxia inducible factor 1, alpha subunit). Results. Analysis
      of relationship between polymorphisms of selected genes and the diagnosis of IHD
      in the whole group of patients with OSAS showed a relationship only for the gene
      SREBF1 finding the lowest frequency of its occurrence in AA homozygotes (at
      13.6%) and twice with GG homozygotes (26.1%). Conclusions. Rating polymorphisms
      studied genes did not reveal their relationship to the occurrence of IHD in
      patients with OSAS, both in the whole group as well as separate subgroups.

PMID- 24868894
TI  - [The effect of 7-ketocholesterol on surface ICAM-1 and PECAM-1 expression in
      human aortic endothelial cells].
AB  - Proatherogenic factors lead to activation of endothelial cells, which symptom is
      an increased expression of surface adhesion molecules enabling the initiation of
      a local inflammatory response. 7-ketocholesterol (7-KCH) is a product of
      oxidation of cholesterol with proven pro-apoptotic effect on the cells of the
      vessel wall. So far, however, the impact of 7-KCH on surface expression of
      adhesion molecules has not been assessed. The aim of this study was to evaluate
      the influence of 7-KCH on the surface expression of adhesion molecules-
      intracellular adhesion molecule 1 (ICAM-1, CD 54) and .platelet endothelial cell
      adhesion molecule 1 (PECAM-1, CD31) on human aortic endothelial cells (HAECs).
      MATERIAL AND METHODS: After treatment with 7-KCH surface expression of adhesion
      molecules on HAEC was measured with antihuman CD31 and anti-human CD54 antibodies
      using flow cytometer. RESULTS: 7-KCH significantly increases percentages of CD 54
      on viable HEAC, but does not affect expression of CD 31. CONCLUSION: 7-KCH may
      enhance the initiation of a local inflammatory response in atherosclerosis by
      increasing the expression of ICAM-1.

PMID- 24868895
TI  - [In the search for effective and safe dose of amikacin in patients with chronic
      kidney disease].
AB  - The aim of the study was to asses safe and effective amikacin (AMK) doses in
      patients with different stages of chronic kidney disease. MATERIAL AND METHODS:
      The study included 25 patients, among them was 12 (48%) men and 13 (52%) women,
      aged 73.1 +/- 11.9 (38-89) years. AMK was applied in intravenous infusion during
      10 days. The dosage was dependent on the stage of chronic kidney disease (CKD).
      Patients in stage 3A CKD (GFR 59--40 ml/min/1.73 m2) received 7.5 mg/kg/day, in
      stage 3B (GFR 39--30 ml/min/1.73 m2) received 4 mg/ kg m.c./day, in stage 4 (GFR
      29--15 ml/min/1,73 m2) received 4 mg/ kg/day or 6.0 mg/kg every two days, in
      stage 5 treated with hemodialysis received 5 mg/kg every two days, in stage 5
      treated with continuous ambulatory peritoneal dialysis received 4 mg/kg every two
      days. Trough levels of the drug (minimal level, before the next dose) and maximal
      levels (one hour after beginning of the infusion) were measured on day 3, 5, 9.
      Hearing tests were done twice, on day 1 and 9. Urine cultures were tested on day
      1 and 5. Complicated urinary tract infections were the reasons of antibiotic
      treatment in 22 patients (88%). Other reasons were: sepsis (2 patients) and
      neutropenic fever (1 patient). RESULTS: Average maximal level of the drug was
      25.5 +/- 8.8 (9.6-50.4) microg/ml, average trough level was 3.1 +/- 2.9 (0.4
      14.1) microg/ml. Bacterial eradication confirmed by negative culture was observed
      in 14 patients (56%). In patients with stage 4 CKD eradication was observed more
      often when AMK was used every day than every two days. Mean trough level was 6.9
      +/- 5.5 microg/ml for every day dosage in comparison with 1.9 +/- 0.5 microg/ml
      for dosage every two days. Mean maximal level was 24.1 +/- 7.2 microg/ml for
      every day dosage and 21.8 +/- 5.8 microg/ml for every two days dosage.
      CONCLUSION: Amikacin usage in described, lowered doses with prolonged interval
      between them is safe in terms of ototoxicity and nephrotoxicity in patients with
      chronic kidney disease. Every two days dosage is less effective than every day
      dosage in patients with stage 4 CKD. It can be a result of too lower minimal
      (trough) levels of the drug in serum. AMK trough levels are associated with
      effective therapy in patients with chronic kidney disease.

PMID- 24868896
TI  - [Assessment of the clinical symptoms and treatment tolerance in patients with non
      small cell lung cancer (NSCLC) undergoing first-line chemotherapy and pulmonary
      rehabilitation].
AB  - In Poland lung cancer is the most commonly occurring cancer type, both in men and
      women. Among the most important concerns related to this disease are clinical
      symptoms caused by deteriorating physical condition and intolerance to
      chemotherapy. The aim of this work was the assessment of the clinical symptoms
      and treatment tolerance in patients with non-small cell lung cancer (NSCLC)
      undergoing first-line chemotherapy and pulmonary rehabilitation. MATERIALS AND
      METHODS: 90 patients with inoperable NSCLC have undergone the examination. This
      included 69 men and 21 women aged between 46-75 years (average age 61.5 +/- 8.2
      years). These were divided into 3 groups: group 1--30 patients undergoing
      standard chemotherapy; group II--30 patients undergoing standard chemotherapy and
      pulmonary rehabilitation; group Ill--30 patients undergoing standard chemotherapy
      and pulmonary rehabilitation with additional vitamin C supplementation. Clinical
      symptoms intensification was assessed using the ESAS scale (Edmonton Symptom
      Assessment System), by comparing the initial score with that after 6 weeks of
      chemotherapy in each individual. RESULTS: In groups II and III, where pulmonary
      rehabilitation was carried out, the intensification of the clinical symptoms and
      lowering of the tolerance for the treatment after 6 weeks of first-line
      chemotherapy were significantly lower (p < 0.05) than in group I. CONCLUSIONS.
      Pulmonary rehabilitation significantly limits the side effects of chemotherapy
      and the deterioration of the state of patients with NSCLC. Simultaneous
      supplementation with ascorbic acid increases the positive effects of pulmonary
      rehabilitation in those patients.

PMID- 24868897
TI  - Blood gas analysis, blood saturation and chosen parameters of spirometric
      examination in NSCLC patients undergoing chemotherapy and pulmonary
      rehabilitation.
AB  - In industrialized countries lung cancer is associated with highest mortality
      among carcinoma. Progression of the disease is associated with diminished
      tolerance for physical activities, aggravated dyspnea and lowering of life
      quality. The aim of study was the evaluation of blood gas, blood saturation and
      chosen parameters of spirometric examination in NSCLC patients undergoing
      chemotherapy and pulmonary rehabilitation. Analysis of capillary blood was done
      using RapidPoint 405 Siemens device. Spirometric examination was done using
      PNEUMO abcMED device. MATERIAL AND METHODS: Forty-nine patients with inoperable
      NSCLC were subjected to the examination. This included 38 men and 11 women aged
      between 46-75 years (mean age 63 +/- 7.5 years) who were separated into two
      groups: group I--25 patients undergoing standard chemotherapy (group C); group II
      -24 patients undergoing standard chemotherapy and pulmonary rehabilitation (group
      CK). All patients were subjected to blood gas analysis, blood saturation analysis
      and spirometric examination twice, before and after first-line chemotherapy
      RESULTS: Increase of pO2 and SaO2 in blood, and FEV1 and FVC in spirometric
      examination was significantly higher in patients undergoing pulmonary
      rehabilitation and chemotherapy (group II) (p < 0.05) in comparison to NSCLC
      patients undergoing only chemotherapy (group I). CONCLUSIONS: Pulmonary
      rehabilitation of NSCLC patients undergoing first-line chemotherapy results in
      improvement of indicators of blood gas, blood saturation analysis and chosen
      parameters of spirometric analysis. Pulmonary rehabilitation in patients with
      lung cancer seems to be an important form of supplementary treatment.

PMID- 24868898
TI  - [The epidemiology of suicide in bipolar disorder in the manic episode-
      preliminary reports].
AB  - Suicide is among ten leading causes of death in each country and the third most
      common cause of death in the age group 16-35. The presence of mental illness is
      the most important risk factor for suicide. Affective disorders contribute to 15
      25% of deaths due to suicide attempts. Depression is the most likely cause of the
      patients attempt on his life. Contrary to popular opinion, manic episode can also
      increase the risk of suicide, especially if the patient dominates by productive
      symptoms in the form of delusions. The aim of study was to determine the
      frequency of suicide attempts and their determinants in an episode of mania in
      bipolar disorder. MATERIALS AND METHODS: The study included 16 people with a
      diagnosed bipolar disorder, hospitalized with manic episode at the age of 28-76.
      Patients hospitalized in the Department of Adult Psychiatry were selected
      randomly. The number of suicide attempts, comorbid conditions, and basic
      epidemiological data were estimated. RESULTS: Five patients declared suicide
      attempt, one of which wanted to make more than one attempt at suicide. 3 people
      took it during an episode of depression, two in an episode of mania. The methods
      of suicide were associated with an overdose of medication and this was
      accompanied by a greater amount of alcohol intake. 11 persons did not declare any
      willingness to attempt suicide. CONCLUSIONS: A mania episode did not increase the
      risk of suicide in bipolar disorder compared to an episode of depression in the
      study conducted. The importance of somatic illness in patients with bipolar
      disorder is increased if the suicide attempt occurs in an episode of depression.
      Alcohol abuse showed no negative effects on suicidal behavior of patients. During
      abuse was the most common way of commit suicide.

PMID- 24868899
TI  - [Isolated tricuspid valve infective endocarditis in a patient with a urological
      history].
AB  - Infective endocardits of the tricuspid valve (TVIE) occurs mainly in addicted
      intravenous drug users, in the presence of intracardiac electrodes or central
      venous catheters, and in some congenital heart diseases; rarely, in other
      conditions. The authors present a case of a 61-year-old male with TVIE as a
      result of complicated transurethral resection of bladder papilloma. The onset of
      TVIE was insidious, with low back pain, followed by pulmonary symptoms.
      Echocardiography showed large vegetations on the tricuspid valve; blood culture
      was positive for methycylin-resistant, coagulase-negative staphylococcus. Fever
      remission and negative bacteriological blood examination results were achieved
      following treatment with linezolid; however, because of advanced tricuspid valve
      destruction, valve replacement was necessary.

PMID- 24868900
TI  - [Refractory hypercalcemia in patient with lung cancer].
AB  - Hypercalcemia is a common complication of malignancy which recognition is usually
      delayed. Severe hypercalcemia can lead to death. Mechanisms of hypercalcemia of
      malignancy include excessive production of parathyroid hormone related protein
      (PTHrP), local osteolysis, absorptive hypercalcemia due to overproduction of
      calcitriol and ectopic parathormone (PTH) production. Volume expansion with
      normal saline solution, loop diuretics and intravenous bisphosphonates are
      mainstays of therapy for hypercalcemia. As an adjunctive therapy calcitonin and
      corticosteroids are used. In refractory cases gallium nitrate and denosumab can
      be an option. In patients with severe acute kidney disease hemodialysis with a
      low-calcium bath is an alternative treatment. In this paper we present a case of
      severe, refractory hypercalcemia in 53-years old patient with squamous cell
      carcinoma of the lung and multiple metastases to bones. Despite intensive
      treatment, that included also intravenous bisphosphonates, patient relapsed on
      therapy and didn't respond to subsequent doses. Patient received subcutaneous
      denosumab with good hypocalcemic effect. In this paper we present pathogenesis
      and treatment of hypercalcemia, including advantages and limitations of
      denosumab.

PMID- 24868901
TI  - [Pancreatic solid pseudopapillary tumor--report of three cases].
AB  - Three cases of young females with pancreatic solid pseudopapillary tumor (SPT)
      were reported. They were referred to Department of Gastroenterology, because of
      the ultrasonographical finding of the pancreatic tale tumor. In all presented
      cases, proper diagnosis was made preoperatively. The patients underwent surgical
      treatment, and remain symptoms-free with no features of recurrence of the disease
      (follow-up from 6 to 36 months).

PMID- 24868902
TI  - [Impact Reimbursement Act on the pharmaceutical market in Poland].
AB  - According to 12 may 2011 Reimbursement Act, the new regulations were introduced
      related to changes in so far in force rules on refunds of official prices and
      margins for drugs, foodstuffs of special purpose and medical products. After year
      of functioning of this regulation, in evaluation of the government, law gave
      measurable financial effects for public payer, sometimes through drastic actions,
      connected the of reduction of existing profits of manufacturers sector and
      importers drugs, as well wholesale and retail, both in treatment open and closed.
      Parallel to research and analysis of effects introduction in life act refund,
      conducted by government, to target current regulation possible negative phenomena
      can to be after-effects to regulation, systematically there are conducted
      analogous study to reputable companies specialized in evaluation and updating
      market Polish pharmaceutical, such as IMS Health Polska, Pharma Expert, Kamsoft,
      WHO and European a law firm. In their opinion to reimbursement act is the most
      serious regulation control system to introduced into Polish order legal, and
      first time for many years on such a large scale. Thoroughly changed policy of
      drugs State have important influence for all participants Polish pharmaceutical
      market, both those directly related to the drug trade, as the functioning doctors
      and health condition and financial Polish patient. Change in the way prices of
      drugs is determined as flexible to price formation mechanism, combining drugs
      similar profile pharmacological in so group limits and dependence of the level of
      refunds from application drug accordingly characteristics medicinal product,
      adaptation solutions to new law refund to the existing law about health services,
      gave measurable financial effect for the public payer. Rationalization expenses
      to NFZ, as main premise introduction refund act, created to broader than so far
      possibility to use new molecules of drugs, and the latest medical technology,
      even if in the revised or new drug programs. Important implications for even
      Polish image in Europe, especially from the point of view of cohesion policy and
      application to directive transparency EU have introduction refund act in context
      to introduction clear, transparent and verifiable procedures used with creating
      drug pricing mechanisms, foodstuffs of special purpose and medical product.

PMID- 24868903
TI  - [Actual diagnosis, treatment and prevention of human granulocytic anaplasmosis].
AB  - Ixodes ricinus tick is widely known as a reservoir and vector for many dangerous
      pathogens. One of them is gram-negative bacteria called Anaplasma
      phagocytophilum, that may cause human granulocytic anaplasmosis (formerly called
      granulocytic ehrlichiosis). Development of modem diagnostics, which allows the
      implementation of effective pharmacotherapy, caused that this disease can be
      effectively detected only for last couple years. Human granulocytic anaplasmosis
      in most cases is not a severe ailment, but in some patients, especially
      improperly diagnosed and treated, it can lead to serious complications or even
      death. Due to non-specific clinical symptoms and a small number of laboratories
      proceeding specialized tests, human granulocytic anaplasmosis constitutes
      clinical and diagnostic problem. A significant increase in tick-borne diseases
      needs to increase public and physicians awareness of these issues.

PMID- 24868904
TI  - [Clostridium difficile infecion--diagnostics, prevention and treatment].
AB  - Clostridium difficile is the most common cause of an antibiotic-associated
      diarrhoea. Frequency of Clostridium difficile infections (CDI) increased in the
      last decade. This study presents current preventive measure i.e. hand washing,
      disposable gloves. Additionally, the article presents diagnostic methods:
      detection glutamine dehydrogenase (GDH), toxins A and B, cytotoxicity
      neutralization test, polymerase chain reaction methods (PCR) i.e. nucleic acid
      amplification test (NAAT) and stool culture. Moreover available methods of
      treatment were presented depending on severity of CDI e.i. metronidazole,
      vancomycin, fidaxomicin, rifaximin. Furthermore, the review provides information
      about alternative methods of treatment in view of new hypervirulent strains of C.
      difficile and increasing resistance to commonly used antibiotics, including:
      fuscid acid, bacitracin, probiotics, non-toxigenic strains, immunoglobulins,
      monoclonal antibodies, vaccines, toxins binders and fecal transplant.

PMID- 24868905
TI  - [Methods of preparation of the platelet-rich plasma used in medicine as an
      accelerator of tissue regeneration].
AB  - Platelet rich plasma is being increasingly used in the modem medicine as a
      material, stimulating regeneration and accelerating tissue healing. Platelet rich
      plasma is an autologous platelet concentrate, which is obtained from the
      peripheral blood of the patient. The method of extraction is based on the
      isolation of platelets during centrifugation of the whole blood, drew on
      anticoagulant. With the difference in density between the various cellular
      components of blood, such as red blood cells, buffy coat and platelet poor
      plasma, the separation into individual fractions is possible. At the present
      moment no optimal method of preparation of the platelet rich plasma has been
      found. On the market there are a number of commercial collection systems
      available, differing from each other in centrifugation parameters, type of
      container to which blood is collected and anticogulant used. Unfortunately, this
      can lead to obtaining platelet rich plasma with a varying number of platelets,
      leukocytes and resulting in a different concentration of growth factors. This is
      important, because the studies show, that a positive clinical effect depends on
      the quality of the used platelet-rich plasma.

PMID- 24868906
TI  - [Dairy products as source of folates].
AB  - Dairy products, especially yoghurts and blue cheeses, are underestimated source
      of folates in human diet. Though foliates content in dairy products is lower than
      in vegetables and cereals, nevertheless their bioavailability and stability is
      much better. High folate stability results from presence of hydro- and lipophylic
      antioxidants efficiently protecting folates and other bioactive compounds against
      oxidation processes on synergic way. On the other hand, high bioavailability is a
      consequence of folic appearing in milk mainly in form of mono glutamates and also
      of a presence of a protein ready to bind folates (FBP--folic binding protein).
      FBP makes easier folates transport through cell membranes. Moreover, present in
      milk sphingolipids and cholesterol stimulate activity of FBP. Mould cheeses and
      milk fermented beverages contain the highest amount of folates. However, cottage
      cheese contain considerable amount of folic binding protein. Regular consumption
      of milk fermented beverages and eating them together with vegetables and fruits
      rich in folates is a chance to increase covering of folic demand.

PMID- 24868907
TI  - [Long non-coding RNAs--"tuning fork" in regulation of cell processes].
AB  - Most of RNA transcripts, instead of serving templates for protein synthesis,
      perform different functions such as control of embryogenesis, differentiation,
      imprinting, X-chromosome inactivation, immune response, and stress reactions. A
      large portion of these RNAs are denoted as long non-coding RNAs (lncRNAs) which
      function as signaling molecules, navigating systems and platforms for ribonucleic
      complexes assembly. They also participate in the organization of specific
      cellular domains. Moreover, they are able to bind regulatory proteins and micro
      RNAs, and serve as precursors for small RNAs. It was shown that lncRNAs
      participate in transcription regulation; they are also involved in alternative
      splicing, RNA editing, traffic, translation and degradation of RNA. The three
      dimensional structure of lncRNAs plays a crucial role in processes of chromatin
      remodeling and transcription regulation. In this review we discuss various
      aspects of lncRNAs functioning.

PMID- 24868908
TI  - [Mechanisms of electron transfer to insoluble terminal acceptors in
      chemoorganotrophic bacteria].
AB  - The mechanisms of electron transfer of association of chemoorganotrophic bacteria
      to the anode in microbial fuel cells are summarized in the survey. These
      mechanisms are not mutually exclusive and are divided into the mechanisms of
      mediator electron transfer, mechanisms of electron transfer with intermediate
      products of bacterial metabolism and mechanism of direct transfer of electrons
      from the cell surface. Thus, electron transfer mediators are artificial or
      synthesized by bacteria riboflavins and phenazine derivatives, which also
      determine the ability of bacteria to antagonism. The microorganisms with
      hydrolytic and exoelectrogenic activity are involved in electron transfer
      mechanisms that are mediated by intermediate metabolic products, which are low
      molecular carboxylic acids, alcohols, hydrogen etc. The direct transfer of
      electrons to insoluble anode is possible due to membrane structures (cytochromes,
      pili, etc.). Association of microorganisms, and thus the biochemical mechanisms
      of electron transfer depend on the origin of the inoculum, substrate composition,
      mass transfer, conditions of aeration, potentials and location of electrodes and
      others, that are defined by technological and design parameters.

PMID- 24868909
TI  - [The effect of ATP-dependent K(+)-channel opener on transmembrane potassium
      exchange and reactive oxygen species production upon the opening of mitochondrial
      pore].
AB  - The effect of mitochondrial ATP-dependent K(+)-channel (K(+)ATP-channel) opener
      diazoxide (DZ) on transmembrane potassium exchange and reactive oxygen species
      (ROS) formation under the opening of mitochondrial permeability transition pore
      (MPTP) was studied in rat liver mitochondria. The activation of K(+)-cycling
      (K(+)-uptake and K(+)/H(+)-exchange) by DZ was established with peak effect at <
      or = 500 nM. It was shown that MPTP opening as well resulted in the activation of
      K(+)-cycling together with simultaneous activation of Ca(2+)-cycle in
      mitochondria. In the absence of depolarization Ca(2+)-cycle is supported by MPTP
      and Ca(2+)-uniporter. The stimulation of K(+)/H(+)-exchange by MPTP opening led
      to the activation of K(+)-cycle, but further activation of K(+)/H(+)-exchange
      resulted in MPTP inhibition. Under the same conditions the decrease in
      mitochondrial ROS production was observed. It was proposed that the decrease in
      ROS formation together with K(+)/H(+)-exchange activation could be the
      constituents of the complex effect of MPTP inhibition induced by K(+)ATP-channel
      opener.

PMID- 24868910
TI  - [Quantitative changes of main components of erythrocyte membranes which define
      architectonics of cells under pttg gene knockout].
AB  - A pttg gene knockout affects the functional state of erythron in mice which could
      be associated with structural changes in the structure of erythrocyte membranes.
      The pttg gene knockout causes a significant modification of fatty acids
      composition of erythrocyte membrane lipids by reducing the content of palmitic
      acid and increasing of polyunsaturated fatty acids amount by 18%. Analyzing the
      erythrocyte surface architectonics of mice under pttg gene knockout, it was found
      that on the background of reduction of the functionally complete biconcave discs
      population one could observe an increase of the number of transformed cells at
      different degeneration stages. Researches have shown that in mice with a pttg
      gene knockout compared with a control group of animals cytoskeletal protein--beta
      spectrin was reduced by 17.03%. However, there is a reduction of membrane protein
      band 3 by 33.04%, simultaneously the content of anion transport protein band 4.5
      increases by 35.2% and protein band 4.2 by 32.1%. The lectin blot analysis has
      helped to reveal changes in the structure of the carbohydrate determinants of
      erythrocyte membrane glycoproteins under conditions of directed pttg gene
      inactivation, accompanied by changes in the type of communication, which joins
      the terminal residue in carbohydrate determinant of glycoproteins. Thus, a
      significant redistribution of protein and fatty acids contents in erythrocyte
      membranes that manifested in the increase of the deformed shape of red blood
      cells is observed underpttg gene knockout.

PMID- 24868911
TI  - [Interaction of DNA nucleotide bases with anticancer drug ThioTEPA: molecular
      docking and quantum-mechanical analysis].
AB  - Using modern methods of molecular docking, quantum chemistry and quantum theory
      of atoms in molecules the interaction of anticancer drug ThioTEPA with isolated
      nucleotide bases and deoxyribonucleosidemonophosphates of DNA has been studied.
      Physical properties and some trends of binding have been established for the
      complexes of "nucleotide base + ThioTEPA" and "deoxyribonucleosidemonophosphate +
      ThioTEPA" types. It has been shown that strong hydrogen bonds of NH...N type are
      the key factor responsible for high selectivity of binding of ThioTEPA to the
      guanine-containing units of the DNA.

PMID- 24868912
TI  - [Stoichiometry of cytochromes and oxygen tension in skeletal muscles of marine
      fish].
AB  - The character of oxygen tension distribution and peculiarities of cytochromes
      stoichiometry in skeletal muscles of bottom and pelagic species of marine fish
      were compared. It is shown, that the limitation of muscle activity increases the
      number of hypoxic zones in the muscle tissue. The mitochondrial electron
      transporting chain then obtain the uncompensated type of organization, expressed
      in the increase of the share of the terminal complex aa3 on the background of
      general reduction of cytochromes content in the muscles. The reaction is of an
      adaptive character and can be implemented by pelagic fish species in conditions
      of experimental hypokinesia.

PMID- 24868913
TI  - [Comparison of bioactive aldehydes modifying action on human albumin].
AB  - Protein's postsynthetic modifications are a cause and a consequence of many
      diseases. Endogenous aldehydes are one of the main factors of these modifications
      formation. The human albumin's modification under some aldehydes influence in in
      vitro experiment has been investigated. Human albumin (20 mM) was incubated with
      following aldehydes: ribose, glyoxal, methylglyoxal and formaldehyde (20 mM each)
      and their combinations in 0.1 M Na-phosphate buffer (pH 7.4) with 0.02% sodium
      azide at 37 degrees C in the dark for up to 30 days. We have determined the
      fluorescent properties of the samples, the content of protein's carbonyl groups
      and the redistribution of protein's molecular weight. The following ratings of
      aldehydes from the lowest to the highest effect have been obtained. Fluorescent
      albumin adducts formation: formaldehyde, methylglyoxal, ribose, glyoxal;
      carbonylation of the protein: ribose, formaldehyde, glyoxal, methylglyoxal;
      polymerization of albumin--the formation of intermolecular crosslinks: ribose,
      methylglyoxal, glyoxal, formaldehyde. The results indicate that these aldehydes
      have different capability for protein's modifications. For example, formaldehyde,
      having the lowest ability to form fluorescent adducts, shows the highest ability
      to form protein's intermolecular crosslinks. Therefore, methods and parameters in
      order to evaluate the protein postsynthetic modification intensity have to be
      chosen correctly according to carbonyl stress peculiarity in order to evaluate
      the protein's postsynthetic modification intensity.

PMID- 24868915
TI  - [Idiotype-antiidiotypic interaction of antibodies in the bloodstream].
AB  - A problem of "prozone" formation in agglutination of corpuscular antibodies by
      bivalent antibodies was considered. Using a new coordinate system, which was
      proposed by us earlier, we analyzed theoretical and experimental curves that
      describe relations between bivalent antibody concentration and some blocking
      factors. It was shown that occupation of antibody paratopes by a blocking factor
      or by antiidiotypic antibodies can induce "prozone" formation. It was also
      demonstrated that experimental titration curves for a mixture of antibodies and
      corresponding antigens coincide with theoretical curves that were calculated
      according to our theory. Our data also demonstrate that major part of serum
      antibodies are blocked by antiidiotypic antibodies when maximum of antibody
      formation is over and antibody titers come down.

PMID- 24868916
TI  - [Identification of small RNA in polyhedra of Bombyx mori nuclear polyhedrosis
      virus].
AB  - It has been shown by bioinformatic methods that regions of the Bombyx mori viral
      nuclear polyhedrosis genome encoded two small RNA--snc RNA-1 and snc RNA-2, which
      could perform a structural function in polyhedra crystals formation. The aim of
      this work was identification of the nucleotide sequence of small non-coding RNAs,
      predicted by bioinformatic methods in B. mori polyhedra. The following methods
      have been used: polymerase chain reaction, agarose gel electrophoresis, the
      cloning of PCR products, sequencing. There were first determined nucleotide
      sequences of snc RNA-1 and snc RNA-2 ofpolyhedrin mRNA complementary regions
      which are included in B. mori polyhedra. These RNAs have 100% identity with
      bioinformatic predicted sequences. These results confirmed our bioinformatic
      approach to the search for small RNAs encoded in B. mori nuclear polyhedrosis
      virus genome.

PMID- 24868914
TI  - [Proteolytic activity of IgG-antibodies of mice, immunized by calf thymus
      histones].
AB  - The main goal of the study was to determine the ability of histones to induce
      production of the proteolytically active IgG-antibodies in BALB/c mice. In order
      to perform this study 8 mice were immunized with the fraction of total calf
      thymus histones. IgGs were isolated from the serum of the immunized and not
      immunized animals by means of precipitation with 33% ammonium sulfate, followed
      by affinity chromatography on protein G-Sepharose column. Histones, myelin basic
      protein (MBP), lysozyme, BSA, ovalbumin, macroglobulin, casein and cytochrome c
      served as substrates for determining the proteolytic activity. It was found that
      IgGs from the blood serum of immunized mice are capable of hydrolyzing histone
      H1, core histone and MBP. On the contrary, the proteolytic activity of IgGs from
      the blood serum of not immunized mice was not detected. The absence of
      proteolytical enzymes in the fraction of IgGs was proven by HPLC chromatography.
      High levels of proteolytic activity toward histones have been also detected in
      affinity purified IgGs from blood serum of patients with rheumatoid arthritis,
      but not in healthy donors. These data indicate that eukaryotic histones may
      induce production of protabzymes in mammals. The possible origin of these
      protabzymes and their potential biological role in mammalians is discussed.

PMID- 24868917
TI  - [Vitamin D3 availability and functional activity of peripheral blood phagocytes
      in experimental type 1 diabetes].
AB  - The study was devoted to identifying the relation between vitamin D3 availability
      (assessed by the level of circulatory 25OHD3), content of vitamin D3 25
      hydroxylase isozymes CYP27A1 and CYP2R1 in hepatic tissue and functional activity
      of peripheral blood phagocytes in mice with experimental type 1 diabetes. It has
      been shown that diabetes is accompanied by the development of vitamin D3
      deficiency which is characterized by decreased 25OHD3 content in blood serum and
      determined by changes in tissue expression of the major isoforms of vitamin D3 25
      hydroxylase. The level of hepatic CYP27A1 was revealed to be markedly reduced
      with a concurrent significant augmentation of CYP2R1. Cholecalciferol
      administration resulted in normalization of tissue levels of both isoforms of
      vitamin D3 25-hydroxylase and blood serum 25OHD3 content. Diabetes-associated
      vitamin D3 deficiency correlated with a decrease in phagocytic activity of
      granulocytes and monocytes, and their ability to produce antibacterial
      biooxidants such as reactive oxygen and nitrogen forms. Vitamin D3 efficacy to
      attenuate these abnormalities of immune function was established, indicating an
      important immunoregulatory role of cholecalciferol in the phagocytic mechanism of
      antigens elimination implemented by granulocytes and monocytes.

PMID- 24868918
TI  - [Comparative analysis of gene expression in normal and cancer human prostate cell
      lines].
AB  - Prostate cancer is one of the main causes of mortality in men with malignant
      tumors. The urgent problem was a search for biomarkers of prostate cancer, which
      would allow distinguishing between aggressive metastatic and latent tumors. The
      aim of this work was to search for differentially expressed genes in normal
      epithelial cells PNT2 and prostate cancer cell lines LNCaP, DU145 and PC3,
      produced from tumors with different aggressiveness and metastatic ability. Such
      genes might be used to create a panel of prognostic markers for aggressiveness
      and metastasis. Relative gene expression of 65 cancer-related genes was
      determined by the quantitative polymerase chain reaction (Q-PCR). Expression of
      29 genes was changed in LNCaP cells, 20 genes in DU145 and 16 genes in PC3 cell
      lines, compared with normal line PNT2. The obtained data make it possible to
      conclude that the epithelial-mesenchymal cell transition took place, which
      involved the loss of epithelial markers, reduced cell adhesion and increased
      migration. We have also found few differentially expressed genes among 3 prostate
      cancer cell lines. We have found that genes, involved in cell adhesion (CDH1),
      invasiveness and metastasis (IL8, CXCL2) and cell cycle control (P16, CCNE1)
      underwent most changes. These genes might be used for diagnosis and prognosis of
      invasive metastatic prostate tumors.

PMID- 24868921
TI  - [Scientists all over the world keep up with the developments in Ukraine].

PMID- 24868919
TI  - [Effect of C60 fullerene on metabolic and proliferative activity of PKE cell
      line].
AB  - The effect of C60 fullerene aqueous colloid solution (C60 FAS) on activity of
      redox and proliferative processes in PKE (transplantable cell line of pig kidney
      embryo) cells has been studied. In particular, it was established that the
      presence of C60 fullerene (127 microM) in culturing medium of PKE cells during 48
      h did not change their ability to reduce non-toxic AlamarBlue redox indicator and
      proliferative activity.

PMID- 24868920
TI  - [Laureates of the Palladin Prize of the National Academy of Sciences of Ukraine
      (1995-1996)].

PMID- 24868922
TI  - The marijuana debate.

PMID- 24868923
TI  - Opioid prescribing primer. Doctors urged to become knowledgeable about risk.

PMID- 24868924
TI  - Reversing tragedy. Proposed legislation will increase access to an antidote to
      opioid overdose.

PMID- 24868925
TI  - Rocky Mountain reality (interview by Kim Kiser).

PMID- 24868926
TI  - Taking a stand. What physicians are saying about legalizing marijuana.

PMID- 24868928
TI  - MMA not support of medical marijuana legislation.

PMID- 24868929
TI  - March madness.

PMID- 24868927
TI  - Medicine or menace? What we know about medical marijuana.

PMID- 24868930
TI  - We need to reschedule cannabis. A sane solution to an irrational standoff.

PMID- 24868931
TI  - Why we need to legalize medical marijuana. One more potential therapy.

PMID- 24868932
TI  - Why we need to be cautious about medical marijuana. Reefer sadness.

PMID- 24868933
TI  - Why the medical community needs to be educated. Medical marijuana--are we ready?

PMID- 24868934
TI  - Medical marijuana--coming soon to a medicine cabinet near you? Where the nation
      stands in terms of legalizing medical cannabis.

PMID- 24868935
TI  - A protocol for addressing acute pain and prescribing opioids.
AB  - Physicians across the country are re-examining their role in the prescription
      opioid abuse problem. In response to growing public awareness about the dangers
      of opioids, the Minnesota Medical Association formed a Prescription Opioid
      Management Advisory Task Force. As part of its work, the task force partnered
      with the Institute for Clinical Systems Improvement (ICSI) to develop a protocol
      for prescribing opioids for acute pain. This article describes the development of
      the new ICSI Acute Pain Assessment and Appropriate Opioid Prescribing Protocol
      and highlights key aspects of the protocol, which emphasizes shared decision
      making and careful, conservative prescribing.

PMID- 24868936
TI  - Forcing a pause. Finding gratitude on our life's journey is an intentional act.

PMID- 24868937
TI  - A call to annual conference.

PMID- 24868938
TI  - Obesity research.

PMID- 24868939
TI  - The baby boom continues.

PMID- 24868940
TI  - Sharps directive.

PMID- 24868941
TI  - The return of the doctor.

PMID- 24868942
TI  - Co awareness.

PMID- 24868943
TI  - Request for good practice examples.

PMID- 24868944
TI  - Ultrasound practioners.

PMID- 24868945
TI  - Screening tests.

PMID- 24868946
TI  - Supporting choice.

PMID- 24868947
TI  - Speaking up.

PMID- 24868948
TI  - Dietary protein intake and risk of GDM.

PMID- 24868950
TI  - A multi-agency approach.

PMID- 24868949
TI  - How to... promote a physiological third stage of labour.

PMID- 24868952
TI  - A lesson learned.

PMID- 24868951
TI  - Spontaneous intrapartum vulvar haematoma.

PMID- 24868953
TI  - Childbirth: a professional struggle.

PMID- 24868954
TI  - C. difficile in pregnancy: an emerging problem.

PMID- 24868955
TI  - [Unresolved issues in the evaluation of research projects involving induced
      pluripotent stem cells (iPS)].
AB  - This paper identifies problems and analyzes those conflicts posed by the
      evaluation of research projects involving the collection and use of human induced
      pluripotent stem cells (iPS) in Spain. Current legislation is causing problems of
      interpretation, circular and unnecessary referrals, legal uncertainty and undue
      delays. Actually, this situation may cause a lack of control and monitoring, and
      even some paralysis in regenerative medicine and cell therapy research, that is a
      priority nowadays. The analysis of the current legislation and its bioethical
      implications, led us to conclude that the review of iPS research projects cannot
      be assimilated to the evaluation of research projects that involve human
      embryonic stem cell (hESC). In this context, our proposal is based on the review
      by the Research Ethics Committees and the checkout by the Spanish Comission of
      Guarantees for Donation and Use of Human Cells and Tissues (CGDUCTH) of human iPS
      cells research projects. Moreover, this article claims for a more transparent
      research system, by effectively articulating the Registry on Research Projects.
      Finally, a model of verification protocol (checklist) for checking out biomedical
      research projects involving human iPS cells is suggested.

PMID- 24868956
TI  - The use of genetic information in the insurance sector--a German perspective.
AB  - The following paper offers an introduction to the legal framework concerning the
      use of genetic information in the insurance sector in Germany. The main contents
      and the controversial issues of the key regulation are examined. The aim of this
      rule being to secure human dignity by respecting the right to informational self
      determination regarding genetic data, including the individual's right not to
      know about their genetic characteristics, there are a number of open issues which
      are being addressed. For instance, the influence of the prohibition to ask for
      genetic testing and to use the results of any such testing by the insurer is
      examined. This examination leads to some explicit results, such as the assumption
      that in addition to the ban on the use of genetic testing no questions about
      family medical history are admissible. The authors embark on the definition of
      genetic testing and the question to what extent the results of diagnostic genetic
      testing may still be made use of in the context of the insured person's
      obligation to display pre-existing conditions and diseases when the contract is
      concluded. In this respect distinctions between diagnostic and predictive genetic
      testing as well as between disease and disposition are drawn. Furthermore, the
      exceptions from the prohibition to use results of genetic testing are examined,
      and the scope of the prohibition of acceptance of results of genetic testing even
      if performed at the instigation of the insured is explored. Finally the
      consequences, encompassing criminal liability and private law ramifications, of
      the violation of the prohibition are presented. In this context, a narrow
      understanding of the aggravated criminal offence of using results of genetic
      testing with the intent to personal enrichment or in return for payments is
      developed. Finally the effects on the validity of the insurance contract and the
      question whether the insurer may be forced to conclude a contract are examined.

PMID- 24868957
TI  - [Incidence of the characteristics of induced pluripotent stem cells in vitro in
      administrative regime of their lines].
AB  - Recently achieved techniques in the field of stem cell research have permitted
      the development of human induced pluripotent stem cells (hiPSCs). The
      characteristics of these cells and their appearance after the passage of Order
      SCO/393/2006, of 8 February, on Functioning and Organization of a National Bank
      of Cell Lines and Act 14/2007, of 3 July, on Biomedical Research raise the
      questions of the legal regime of their deposition at the National Bank of Cell
      Lines and their control by the Commission of Guarantees for the Donation and Use
      of Human Cells and Tissues. Drawing on a wider legal frame, the author defends
      these requirements on the grounds that the legal classification comes from the
      origin and potentiality of the cells rather than from the techniques employed to
      obtain them.

PMID- 24868958
TI  - [Patentability of DNA sequences: the debate remains open].
AB  - The patentability of human genes was from the beginning of the discussion
      concerning the Directive on the legal protection of biotechnological inventions,
      an issue that provoked debates among politicians, scientists, lawyers and civil
      society itself. Although Directive 98/44 tried to settle the matter by stating
      that to support the patentability of human genes, it should know what role they
      fulfill, which protein they encode, all of this as an essential requirement to
      test its industrial application. However, following the judgment of 13 June 2013
      (Supreme Court of the United States of America in the case of Association for
      Molecular Pathology et al. versus Myriad Genetics Inc.) the debate on this issue
      has been reopened. There are several issues to be considered, taking into account
      that the patents on DNA & Gene Sequences have played an important incentive to
      increase the interest in biotechnology applied to human health. On the other
      hand, this is a paradigm shift in the R & D of biopharmaceutical companies, and
      it has moved from an in house research model to a model of open innovation, a
      model of collaboration between large corporations with biotech SMEs and public
      and private research centers. This model of innovation, impacts on the issue of
      the industrial property, and therefore it will be necessary to clearly define
      what each party brings to the relationship and how they are expected to share the
      results. But all of this, with the ultimate goal that the patients have access to
      treatments and medications most innovative, safe and effective.

PMID- 24868959
TI  - [U.S. Supreme Court ruling on patentability of genes].
AB  - This paper involves a critical commentary concerning the judgment of the U.S.
      Supreme Court 13/06/2013 on the patentability of human genes. In the author's
      opinion, the judgment reaffirms a favorable position to a current school of
      thought whereby protecting "biotechnological innovations" distorts the patent
      law.

PMID- 24868960
TI  - [Comment on the Maryland vs King ruling of the Federal Supreme Court of the
      United States of America (3-VI-2013)].
AB  - In the present work, the opinion of the Supreme Court of the United States (June
      3, 2013) on the constitutionality of the mandatory DNA testing of offenders is
      analyzed, on the basis of Maryland vs. King Case. This case reveals the
      increasing complexity involving genetics and the handling of personal
      information. On the one hand, the possibility of solving complex crimes is
      facilitated by this way. In this sense, genetic testing has proved particularly
      valuable in determining forms of participation in crime, to help identify the
      coincidence or not of a DNA sample taken from the individual with genetic traces
      which are present at the crime scene. But on the other hand, privacy is at stake
      with the possibility of an abuse of this information.

PMID- 24868961
TI  - [Accessing medical records for research purposes].
AB  - The Organic Law 15/1999 of 13 December on the Protection of Personal Data and the
      Law 41/2002 of 14 November regulating patient autonomy and rights and obligations
      of information and clinical documentation are the basic rules which govern the
      medical history in Spain. However, the lack of development of these laws
      regarding data protection in clinical research, particularly in terms of access
      to the medical history, repeatedly causes doubts about its construction by the
      Research Ethics Committees. Therefore, the aim of this paper is to analyze the
      rules which govern the access to the medical history for research purposes, with
      particular emphasis on the common problems that arise in the Committees for the
      ethical evaluation of these projects and finally setting a series of
      recommendations. The use for research purpose of genetic personal data contained
      in the medical history is also addressed in this paper. In this sense, a key
      contribution of the Law on Biomedical Research is relating to the specific
      regulation of the genetic personal data, both with respect to their production
      and access to the data as a support and regarding to its use for research
      purpose.

PMID- 24868962
TI  - [Update of the work of the ethics research in evaluating genetic research and its
      role as an external ethics committee biobank].
AB  - Research on human genome and its applications open great perspectives to improve
      human beings' health. However, these advances must never endanger the respect of
      dignity, freedom and rights of the participants in medical research, assuring
      prohibition of any way of discrimination because of genetic features. The
      Independent Research Boards (IRB), responsible for safeguarding rights, safety
      and well-being of the subjects taking part in the biomedical research, assess
      independently submitted genetic studies, clinical trials whose primary objective
      is obtaining genetic information and genetic sub-studies of clinical trials with
      drugs. Biobanks, as safeguarding means to preserve biological samples in suitable
      quality conditions, must be assigned to two external committees, a scientific one
      and an ethics one. External ethics committees of biobanks have to make the
      ethical assessment of the submissions of samples transfers and associated data,
      in order to carry out research projects. On the other hand, they have to advise
      biobanks on the compliance of ethical and legal principles, which, in many
      committees, has turned into the performance of informed consent forms which are
      in accordance with current laws.

PMID- 24868963
TI  - Supreme Court of the United States Syllabus: Maryland v. King Certiorari to the
      Court of Appeals of Maryland.

PMID- 24868964
TI  - [Evaluation on the iron absorption of prepubertal children using stable isotopic
      tracer].
AB  - OBJECTIVE: To investigate the iron absorption of prepubertal children using
      stable isotopic tracer. METHODS: 57 subjects were orally given 57FeSO4, in
      conventional diet mode, before breakfast and supper and totally for 5 days. All
      the fecal during the specified time were collected, pre-conducted and determined
      by AAS and MC-ICP-MS to evaluation the iron absorption of prepubertal children.
      RESULTS: The iron absorption rate of male and female were (26.71 +/- 2.94)% and
      (29.76 +/- 2.20)%, and the correction absorption rate of iron were (27.45 +/-
      2.83)% and (31.01 +/- 2.48)%, absorption of female were higher than that of male
      (P < 0.05). CONCLUSION: In the condition of fasting oral SI, there is a high iron
      absorption rate of prepubertal children, and absorption rate of female is higher.

PMID- 24868965
TI  - [Rapid detection of Listeria monocytogenes in pork samples by real-time PCR with
      Taqman probe].
AB  - OBJECTIVE: To develop a real-time PCR method for detection Listeria monocytogenes
      in pork samples. METHODS: Listeria monocytogenes specific primers and Taqman
      probe were chosen on the basis of hlyA gene. Real-time PCR method was developed
      and its specificity was proved. Serial 10-fold diluted pure suspension culture of
      CMCC 540004 were detected by real-time PCR, and standard curve was constructed.
      Artificially contaminated experiment was done, six artificially-inoculated
      samples containing final concentration of Listeria monocytogenes CMCC 540004 (1.3
      x 10(0), 1.3 x 10(1), 1.3 x 10(2), 1.3 x 10(3), 1.3 x 10(4), 1.3 x 10(5) and 1.3
      x 10(6) CFU per 25 g pork samples) were preparated respectively, meanwhile one
      sample without inoculation was as control of background value. All the samples
      were incubated in LB1 enrichment for 24 h and then take 0.1 ml culture solutions
      to 10 ml LB2 enrichment for 18 - 24 h. All the samples were incubated for 0, 4,
      8, 12, 18, 24, 30, 36 and 46 h, and detected Listeria monocytogenes bacteria by
      PCR, respectively. Twenty-four samples of retail pork were collected from markets
      in Beijing and detected by the above three methods. RESULTS: Real-time PCR method
      established was specific for the detection of Listeria monocytogenes. The
      sensitivity was 1.3 x 10(3) CFU/ml for pure culture without enrichment. Real-time
      PCR detection limit for artificially contaminated samples after enriching for 24
      h was 1.3 CFU/ 25 g, which is the same with the limit of PCR and traditional
      method after enrichment for 46 h. Standard curve of sample after enrichment for
      24 h was established. The positive rate out of total 24 samples was 70.83%
      (17/24) by real-time PCR, which is the same with the result of PCR and
      traditional method. The positive ones were quantitative analyzed using standard
      curve of sample and determined the initial Listeria monocytogenes numbers of
      CFU/25 g. CONCLUSION; The established real-time PCR technology was simple, rapid,
      sensitive and specific, which was suitable to rapid detect Listeria monocytogenes
      in pork samples and the process was finished in 27 h.

PMID- 24868966
TI  - [Effects of octreotide on fatty infiltration of the pancreas in high-fat diet
      induced obesity rats].
AB  - OBJECTIVE: To investigate effects of octreotide on fatty infiltration of the
      pancreas in high-fat diet induced obesity rats. METHODS: SD rats were divided
      into control group (n = 14) and high-fat diet group (n = 36). Obese rats from the
      high-fat diet group were further divided into 2 groups: the obese group (n = 14)
      and the octreotide-treated group (n = 16). Rats in the octreotide-treated group
      were subcutaneously injected with octreotide per 12 h (40 mg/kg BW) for 8 days.
      Body weight, fasting plasma glucose (FPG), fasting serum insulin, triglyceride
      (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C)
      levels, pancreatic TG and FFA content were measured. Homeostatic model assessment
      (HOMA) index was calculated. Somatostatin (SST) and the expression of adipose
      differentiation-related protein (ADFP) in pancrea were measured. Pathological
      changes of pancreas were examined with light microscopy. RESULTS: Body weight,
      Lee's index, FPG, fasting serum insulin, TG, TC levels and HOMA index in the
      obese group were higher than those in the control group (P < 0.05), while the
      level of HDL-C in the obese group was lower than that in the control group (P <
      0.05). Pancreatic TG, FFA contents and expression of ADFP in the obese group were
      significantly higher than those in the control group (P < 0.05), while pancreatic
      SST level in the obese group was lower than that in the control group (P < 0.05).
      Obvious pancreatic intra-lobular fatty infiltration was observed in the obese
      group. After treatment of octreotide, body weight, HOMA index, as well as other
      plasma parameters as above showed decrease as compared with those in the obese
      group (P < 0.05). In addition, pancreatic TG, FFA contents and the expression of
      ADFP in the octreotide treated group were also significantly decreased compared
      with those in the obese group (P < 0.05), pancreatic SST level was increased in
      the octreotide treated group than that in the obese group (P < 0.05), and
      pancreatic intra-lobular fatty infiltration was alleviated. CONCLUSION:
      Octreotide might improve pancreatic fatty infiltration, lipid disorder, insulin
      resistance and alleviate pancreatic injury by down-regulating the expression of
      ADFP in pancreas, and lowering the levels of plasma glucose and lipid in the high
      fat diet induced obesity rats.

PMID- 24868967
TI  - [Roles of p53 in the interaction of p21 and cell cycle proteins induced by benzo
      [a] pyrene].
AB  - OBJECTIVE: To investigate the roles of p53 in the interaction of p21, cyclin D1
      and CDK4 in human embryonic lung fibroblasts (HELFs) induced by benzo (a) pyrene.
      METHODS: p53-H group (cells transfected with p53 small interference RNA plasmid,
      p53 siRNA) and HELF/CMV group (cells transfected with CMV vector) were treated
      with 2 micromol/L B [a] P for 24 h, and HELF/CMV + PFT-alpha group (HELF/CMV
      cells were treated with p53 chemical inhibitor, Pifithrin-alpha) was treated with
      2 micromol/L B [a] P and 20 micromol/L PFT-alpha for 24 h. The above three groups
      set up control groups, respectively. Western blot assay was used to check the
      levels of p53, phosphorylated p53 at 20 site (p53-ser20), p21, cyclin D1 and
      CDK4. Immunoprecipitation assay was used to investigate the roles of p53 in the
      interaction of p21, cyclin D1 and CDK4. RESULTS: After inhibition of p53 using
      PFT-alpha or siRNA, the high levels of p53, p53-ser 20 and p21 induced by B [a] P
      were markedly decreased. The change of cyclin D1 level was not obsevered and the
      level CDK4 was free of B [a] P. The combination of p21 and CDK 4 was increased
      after HELFs exposed to B [a] P, which can not be observed after inhibition p53.
      The combination of p21 and cyclin D1 was increased with or without the expression
      of p53 after HELFs exposed to B [a] P. The combination of cyclin D1 and CDK 4 was
      not affected by B [a] P. CONCLUSION: p53 can affect the combination of p21 and
      CDK4 in HELFs induced by B [a] P.

PMID- 24868968
TI  - [Roles of ceruloplasmin in silica-induced JNK/ERK/AP-1 cell signaling pathway
      change].
AB  - OBJECTIVE: To investigate the roles of ceruloplasmin (Cp) in JNK/ERK/ AP-1 cell
      signaling pathway change in human embryonic lung fibroblasts (HELFs) induced by
      silica. METHODS: Cp stimulated HELFs in different time points (before 1 h,
      accompanied with or after 1 h of silica-adding). HELFs were divided into these
      groups: control group, silica(100 microg/ml for 24 h) group, Cp (30 microg/ml for
      24 h) group and silica plus Cp (100 microg/ml silica plus 30 microg/ml Cp) group.
      DN-JNK cells and DN-ERK cells (cells were transfected with dominant negative
      mutant plasmid) contained these groups: control group, silica group, silica plus
      Cp group. MTT assay was used to detect the effects of Cp on silica-induced cell
      proliferation. Western blot assay was performed to detect the levels of JNK, ERK,
      c-Jun, c-Fos and their phosphorylated levels. RESULTS: Cp promoted cell
      proliferation induced by silica when silica stimulated HELFs 1 h then adding to
      Cp. Cp significantly increased silica-induced the high levels of JNK, ERK and
      phosphorylated JNK (p-JNK), p-ERK, p-c-Jun and p-c-fos protein. After inhibition
      of JNK or ERK, silica-and-Cp-induced cell proliferation was markedly decreased.
      When suppressing JNK protein, the increased levels of p-JNK, p-c-Jun and p-c-fos
      protein was not observed. The high levels of p-ERK, p-c-Jun and p-c-fos protein
      were decreased when inhibiting ERK protein. CONCLUSION: Cp could further
      strengthen silica-induced cell proliferation by JNK/c-Jun/c-Fos and ERK/c-Jun
      cell signaling pathway.

PMID- 24868970
TI  - [Optimization of culture condition for cultivation of influenza virus A on MDCK
      cell].
AB  - OBJECTIVE: To optimize the cultivation condition of influenza virus A on MDCK
      cells and to improve the separation rate and the inspected effect of influenza
      virus. METHODS: The virus specimens which came from three kinds of the influenza
      virus A, swine-origin H1N1, seasonal H1N1 and seasonal H3N2, were cultivated by
      MDCK cells. It will make the most suitable condition by means of comparing the
      different inoculum size (25, 50, 75, 100, 125 and 150 microl/cm2), the different
      concentration of TPCK-Trypsin (1.0, 1.5, 2.0, 2.5, 3.0 and 3.5 microg/ml) as an
      addition and the different susceptibility of cell generations for serial passage
      culture of four generations of these three influenza virus. RESULTS: Throughout
      the comparison the three kinds of the influenza virus, swine-origin H1N1,
      seasonal H1N1 and seasonal H3N2, which had the most suitable inoculum size
      100,75, 75 microl/cm2 and the most suitable concentration of TPCK-Trypsin as an
      addition 2.5, 2.0, 2.0 microg/ml and the most suitable generations of cell 1, 2,
      2 respectively. Earlier generations of MDCK cells of the swine-origin H1N1 were
      more susceptible than the other influenza virus A. The hemagglutination
      inhibition (HI) of swine-origin H1N1 after cultivated was lower than the other of
      seasonal H1N1 and seasonal H3N2. CONCLUSION: The separating effect of the swine
      origin H1N1 virus in the MDCK cell was inferior to the seasonal H1N1 and seasonal
      H3N2. The culture condition of seasonal H1N1 and seasonal H3N2 were roughly
      similar.

PMID- 24868969
TI  - [Research on the sodium arsenite and arsenic trioxide induced proliferation and
      apoptosis effects on human hepatocyte].
AB  - OBJECTIVE: To explore the proliferation and apoptosis effects induced by sodium
      arsenite and arsenic trioxide on human hepatocyte L02 and provide evidence for
      the paradox effects of arsenic. METHODS: Human hepatocyte L02 was treated by a
      series of concentration of sodium arsenite or arsenic trioxide, respectively.
      Cytotoxicity were tested by MTT assay and colony formation assay, cellular
      apoptosis and cell cycle were detected by flow cytometry, chromosomal breakage
      were measured by micronucleus test and reactive oxygen species level and GSH
      contents were detected with commercial kits. RESULTS: With the increase of sodium
      arsenite or arsenic trioxide concentrations, cellular viability, colony formation
      rate and GSH contents decreased; inhibition of colony formation, cellular
      apoptotic rate, reactive oxygen species level and frequency of micronuclei
      increased, and dosed cells were both arrested in G2/M phase of cell cycle.
      CONCLUSION: Both sodium arsenite and arsenic trioxide could induce oxidative
      stress in human hepatocyte L02 and result in chromosomal damage, apoptosis, cell
      cycle arrest and cellular proliferation inhibition, suggesting that oxidative
      stress induction might be the common molecular mechanism of malignant
      transformation induced by sodium arsenite and therapeutic effects exhibited by
      arsenic trioxide.

PMID- 24868971
TI  - [The inherent toxicity of organic extracts in the effluents treated by present
      treatment and the new process].
AB  - OBJECTIVE: Evaluate the inherent toxicity of organic extracts in the effluents
      treated by present treatment and the new process find the scientific evidences of
      the new wastewater treatment technique to compare the removal efficiency of trace
      organic pollutants. METHODS: The Solid Phase Extraction was adopted to enrich the
      trace organic pollutants in the water samples with resin adsorbing, then detected
      the inherent toxicity of them by using Vicia faba root-tip micronucleus test and
      single cell gel electropheorsis test. RESULTS: After concentrated 100 times, the
      organic extracts enriched from the water samples showed some positive reactions.
      The micronuclear rates of root-tip cells were of significantly difference between
      all groups (F = 42.526, P < 0.001). Compared with each other, the group of DMSO
      and the group of new technique were not significantly different from the negative
      control (P > 0.05), but the group of secondary effluent and the group of influent
      were significantly different from the new technique (P < 0.05), at last, there
      was significant difference between the secondary effluent and the influent (P <
      0.05). After exposed with DMSO and the organic extracts, the length of comet
      tails and the tailing ratio were obviously different between all groups (F =
      243.535 and 148.623 correspodingly, P < 0.001). Compared with negative control,
      the length of comet tails and the tailing ratio of the influent group and the
      secondary effluent group were significantly different (P < 0.01). Compared with
      the influent group, the comet tail length of the secondary effluent group and the
      tertiary effluent group were both shorter (P < 0.01), and the tailing ratio were
      both smaller (P < 0.01). The tailing ratio of the tertiary effluent group was
      significantly smaller than the secondary effluent group. CONCLUSION: The inherent
      toxicity of urban sewage in Zhengzhou was significantly decreased after treated
      but it still possesses potential hazard to environment. And the trace organic
      pollutants in wastewater were removed by the new technique more efficiently than
      by the present treatment.

PMID- 24868972
TI  - [Study on the prevalence of childhood overweight and underweight, and the
      association with family socio-economic status (SES)].
AB  - OBJECTIVE: To analysis the prevalence of childhood overweight and underweight,
      and the association with family socio-economic status (SES) over years. METHODS:
      Children aged under 18 years in nine province of China were analyzed from the
      datasets of 1991 - 2009 China Health and Nutrition Survey. SES were indicated bu
      per capita family income and parental tertiary education. The time trends of the
      associations between SES and childhood overweight and underweight were analyzed
      by Logistic regression, and the correlation between SES and childhood BMI were
      estimated by Quantile regression. RESULTS: The prevalence of overweight and
      underweight have increased by 1.22 times and 0.39 times, respectively. Logistic
      regression results show that family income per capita changed from a protective
      factor for childhood overweight into a risk factor over almost two decades, while
      parental tertiary education increased the odds more prominent. For childhood
      underweight, the SES indicators show no statistically significant effect.
      Estimations from Quantile regression also show the same pattern with Logistic
      results. CONCLUSION: Both of childhood overweight and underweight were affected
      by family income and parental tertiary education. A comprehensive prevention and
      control measures of family intervention should be taken.

PMID- 24868973
TI  - [Analysis on the iron deficiency and the rate of anemia of 3-11 year old children
      in 7 cities and 2 countryside in China].
AB  - OBJECTIVE: To investigate the status of iron deficiency and the rate of anemia of
      3 - 11 year-old children in Chinese cities and countryside and explore the
      possible related influencing factors. METHODS: The multistage stratified cluster
      random sampling was used to select one kindergarten and one primary school in
      seven cities (Beijing, Shenyang, Suzhou, Zhengzhou, Chengdu, Lenzhou and
      Guangzhou) and two countryside randomly in Hebei Province one bottom class,
      middle class, top class in one kindergarten and one second grade and fifth grade
      in one primary school were selected randomly. All of the healthful students of
      these classes were investigated and the element iron and the parameters of red
      blood cell were detected. RESULTS: 1863 students in 7 cities and 2 countryside
      were investigated in the research. The incidence of iron deficiency of different
      ages had statistical significance and with the age increasing, the incidence
      showed a decreasing trend. The incidences of iron deficiency were 47.1% and 38.2%
      in 3 -4 year-old children and 4 - 5 year-old children, respectively. The
      incidence of anemia of different ages had statistical significance. The
      incidences of anemia of 3 - 4 year-old children and 4 -5 year-old children were
      significantly higher than those of 5 - 6 year-old children. The incidences of
      anemia were 4.0% and 7.1% in 3 - 4 year-old children and 4 -5 year-old children,
      respectively. No statistical significance for different sex of the same age was
      found for iron deficiency and anemia incidence. The incidence (12%) of anemia of
      the children in countryside area was significantly higher than those in first
      tier cities and second-tier cities. CONCLUSION: The status of iron deficiency and
      the rate of anemia of 3 - 11 year-old children in Chinese cities and countryside
      were improved recently, but still serious. It should be paid more attention to
      the children with lower serum iron content and the children in rural areas.

PMID- 24868974
TI  - [Study on the correlation between serum lipid and serum carnitine palmitoyl
      transferase 1A in rural adults over 40 years in Tianjin].
AB  - OBJECTIVE: To explore the status of serum lipids and analyze its relationship
      with carnitine palmitoyl transferase 1A (CPT1 A) in rural people over 40 in
      Tianjin, China. METHODS: By cluster multi-stratified sample of 719 people over 40
      was investigated with a questionnaire from rural areas in Tianjin. And finally
      draw a conclusion based on data analysis from fasting blood and measured total
      cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C)
      and CPT1 A. RESULTS: In this research, the rate of dyslipidemia was 46.73%, in
      which 48.22 percent male and 45.41 percent female, a nonsignificant difference.
      CPT1 A correlated with TC, LDL-C were 0.123 and 0.130, with simple linear
      regression, and there was only significant difference between LDL-C and CPT1 A by
      multiple regression analysis. CONCLUSION: There is a high rate of dyslipidemia
      among the rural people over the age of 40 in Tianjin, and the CPT1 A is closely
      associated with serum lipid.

PMID- 24868975
TI  - [Study on the association between diet, nutrient and attention deficit
      hyperactivity disorder among children in Shanghai, Kunshan, Wuxi three
      kindergarten].
AB  - OBJECTIVE: To explore the correlation between nutrition and children with
      attention deficit hyperactivity disorder (ADHD). METHODS: For 417 students from
      Shanghai and Jiangsu Province, Conners Parent Symptom Questionnaire was used to
      investigate learning disorders and Food Frequency Questionnaire was used to
      evaluate the dietary and nutrient intake. Correlation between ADHD and Diet was
      analyzed. RESULTS: The rate of the ADHD abnormalities was 3.2%, there was no
      statistical difference between both the various regions and the genders. Partial
      correlation analysis showed that there was a positive correlation between diet
      intake (processed meat, salty snacks) and hyperactivity index (P < 0.05); A
      negative correlation was found between vegetables, coarse cereals, aquatic
      products, beef, mutton, milk and hyperactivity index (P < 0.05). The regression
      showed that there was a negative correlation between calcium and hyperactivity
      index (P < 0.05). CONCLUSION: Children's diet pattern is an important
      environmental impact foctor for ADHD.

PMID- 24868976
TI  - [Research on relations among self-esteem, self-harmony and interpersonal-harmony
      of university students].
AB  - OBJECTIVE: To learn characteristics and their mutual relations of self-esteem,
      self-harmony and interpersonal-harmony of university students, in order to
      provide the basis for mental health education. METHODS: With a stratified cluster
      random sampling method, a questionnaire survey was conducted in 820 university
      students from 16 classes of four universities, chosen from 30 universities in
      Anhui Province. Meanwhile, Rosenberg Self-esteem Scale, Self-harmony Scale and
      Interpersonal-harmony Diagnostic Scale were used for assessment. RESULTS: Self
      esteem of university students has an average score of (30.71 +/- 4.77), higher
      than median thoery 25, and there existed statistical significance in the
      dimensions of gender (P = 0.004), origin (P = 0.038) and only-child (P = 0.005).
      University students' self-harmony has an average score of (98.66 +/- 8.69), among
      which there were 112 students in the group of low score, counting for 13.7%, 442
      in that of middle score, counting for 53.95%, 265 in that of high score, counting
      for 32.33%. And there existed no statistical significance in the total-score of
      self-harmony and score differences from most of subscales in the dimention of
      gender and origin, but satistical significance did exist in the dimention of only
      child (P = 0.004). It was statistically significant (P = 0.006) on the
      "stereotype" subscales, on the differences between university students from urban
      areas and rural areas. Every dimension of self-esteem and self -harmony and
      interpersonal harmony was correlated and statistically significant. Multiple
      regression analysis found that when there was a variable in self-esteem, the
      amount of the variable of self-harmony for explaination of interpersonal
      conversation dropped from 22.6% to 12%, and standard regression coefficient
      changing from 0.087 to 0.035. The trouble of interpersonal dating fell from 27.6%
      to 13.1%, the standard regression coefficient changing from 0.104 to 0.019. The
      bother of treating people fell from 30.9% to 15%, and the standard regression
      coefficient changing from 0.079 to 0.020. The problem of heterosexual contact
      fell from 23.4% to 17.3%, and the standard regression coefficient changing from
      0.095 to 0.024. CONCLUSION: Self-esteem was a mediator variable between self
      harmony and interpersonal-harmony. By cultivating university students' level of
      self-esteem to achieve their self-harmony and interpersonal-harmony, university
      students' mental health level can be improved.

PMID- 24868977
TI  - [Investigation research of occupational stress and job burnout for oil field
      workers in Xinjiang].
AB  - OBJECTIVE: To provide scientific basis for further intervention, the association
      between occupational stress and job burnout among oil field workers of Xinjiang
      was discussed. METHODS: A random sample and research on Xinjiang oil-field
      outdoor workers who will finish occupation Stress Inventory-Revised questionnaire
      and Maslash Burnout Survey. RESULTS: The scoring of each OSI-R dimension and each
      MBI dimension varied significantly between different individual characterizations
      (age, gender and education). Multiple linear regression analysis showed:
      occupation task, physical strain, work environment, subjective support, self
      health care are the main factors influencing occupation burnout. CONCLUSION:
      Different individual characteristics effect the occurrence of occupation stresses
      and job burnout, reduce the occupation task, strengthen social support and self
      health care consciousness, strive to build and improve the enterprise culture
      atmosphere can prevent occupation burnout.

PMID- 24868978
TI  - [Status and trend for sodium content of Chinese per-packaged foods].
AB  - OBJECTIVE: To collect the data on the sodium content of Chinese per-packaged
      foods, and to analyze the variation trend of sodium content. METHODS: 1279 data
      on the sodium content of per-packaged foods in all were recorded and analyzed
      through the investigation of per-packaged food nutrition labels, and were
      categorized into 31 varieties. Median sodium content and variation were
      calculated for each variety and compared with 2004 sodium content data on China
      Food Composition. RESULTS: There are 6 per-packaged foods varieties has the
      median sodium content more than 500 mg/100 g. The food varieties with the highest
      mean sodium content were ready-to-eat food(2500 mg/100 g), followed by instant
      noodles (1900 mg/100 g). Compared with 1991 -2004 per-packaged foods sodium
      content, 13 varieties had medium sodium content that increased, and 5 varieties
      increased significantly, such as cake, liquid milk, instant noodles etc.
      CONCLUSION: The survey show that sodium content of some per-packaged food
      increased.

PMID- 24868979
TI  - [MTHFR C677T polymorphism and genetic susceptibility of esophageal cancer and
      esophageal precancerous lesions].
AB  - OBJECTIVE: To study the association between methylene tetrahydrofolate reductase
      (MTHFR) C677T polymorphism and esophageal cancer risk. METHODS: esophageal cancer
      cases, 150 esophageal precancerous lesions cases and 207 healthy controls were
      selected in a high esophageal cancer incidence region in Huai'an, China. MTHFR
      genotypes at the C677T site were analyzed by polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) methods. Chi-square test was
      used to estimate MTHFR genotype frequency distribution in the control, esophageal
      precancerous lesions (mild, moderate and severe) and esophageal cancer groups.
      RESULTS: MTHFR C677T genotype distributions in the control and esophageal cancer
      groups had no significant differences. There was a significant difference in the
      frequency distribution of MTHFR 677TT genotype and T allele between the
      esophageal precancerous lesions group and the control group (P < 0.05). Compared
      with the mild group, the MTHFR 677TT genotype distribution in the moderate or
      severe esophageal precancerous lesions groups and T allele in the moderate group
      had significant differences (P < 0.05). CONCLUSION: There may be no correlation
      between the MTHFR C677T gene polymorphism and susceptibility to esophageal
      cancer, but it had correlation with susceptibility to esophageal precancerous
      lesions. Individuals with MTHFR 677TT variant genotypes and T allele were at
      higher risk of esophageal precancerous lesions.

PMID- 24868980
TI  - [Combined effects of sub-chronic exposure to lead and cadmium on physiological
      and biochemical indexes of blood in SD rats].
AB  - OBJECTIVE: The combined subchronic effects of exposure to lead acetate [Pb
      (NO3)2] and cadmium chloride [CdCl2 x 2.5H2O] on blood physiological and
      biochemical indexes of rats were detected to investigate the hazards of
      environmentally relevant, low-dose exposure to these compounds. METHODS: 80 SD
      rats were randomly divided into three experiment groups and one control group.
      The rats in the three experiment groups were orally administrated with Pb(NO3)2
      and CdCl2 x 2.5H2O combined solution at the doses of 29.96, 89.88 and 269.65
      mg/kg for 90 days respectively, and the rats in control group were orally
      administrated with water. Blood were collected every 30 days to determine
      physiological and biochemical indexes. RESULTS: In each poisoning groups, WBC,
      RBC and HGB increased during early experiment period and then decreased. ALT, AST
      and BU increased all the experiment time. GLU decreased in the experiment time.
      Compared with control group, TC increase at high-dose poisoning group and TG
      decrease at low-dose poisoning group. The TP, ALB, GLO and CRE in the poisoning
      groups were not significantly different from those in the control group. And the
      hepatic cells and renal tubule epithelial cells showed granular degeneration,
      vacuolar degeneration and necrosis in poisoning groups. CONCLUSION: Low-dose Pd
      Cd combined exposure could significantly change physiological and biochemical
      indexes of blood and cause hepatic and renal pathological injury of SD rats.

PMID- 24868981
TI  - [Reproductive toxicity of ethylparaben on male Drosophila melanogaster].
AB  - OBJECTIVE: To investigate the reproductive toxicity of different concentration of
      ethylparaben (EP) on male Drosophila. METHODS: New eclosion flies within 8h in
      the basal medium were collected and male Drosophila among them were put into
      control group and EP treating groups with different concentration (0.03%, 0.07%
      and 0.10%) by random selection. Female Drosophila was all put into control group.
      After cultured for 5 days by one pair in one tube and 10 times of repetition for
      each group, the egg laying amount and maximum egg laying amount of 10d parental
      generation (F0) and first filial generation (F1), the emergence rate and
      emergence amount of F1 and second finial generation (F2), the duration time of
      eggs-arvae, larvae-pupa, and pupa-adult flies, and the total duration time of
      emergence were counted. RESULTS: The egg laying amount, emergence rate and
      emergence amount of EP treated parental Drosophila were significantly lower than
      those of the control group (P < 0.01). The total duration time of emergence of F1
      prolongs with the increase of EP concentration. The egg laying amount of F1 and
      emergence rate of F2 in high EP concentration group had remarkable different
      compared to those of control group (P < 0.01). And the total duration time of F2
      had also shortened significantly compared to that of control group (P < 0.05),
      while there was no remarkable difference in 0.03% and 0.07% concentration group.
      CONCLUSION: EP has a certain reproductive toxicity to F0 male Drosophila and EP
      of high concentration can impact sustainable to offspring which has some
      facilitation effect on F1 Drosophila.

PMID- 24868982
TI  - [Effect of rich-D-transallethrin on amino acid neurotransmitters in rat brain].
AB  - OBJECTIVE: To discuss the effect of rich-D-transallethrin on amino acid
      neurotransmitters in rats central nerves system and pathological examination of
      brain tissues, hypophysis and sciatic nerve. METHODS: Ninety-six male and female
      Wistar rats were randomly divided into four groups according to body weight,
      which were exposed to rich-d-transallthrin aerosol at different dose (0, 9.6,
      45.8, 166 mg/m3) for 6 h/d, 7 d/week for 28 consecutive days. Neurobehavior were
      observed, gait and grip strength were measured during exposure. At the end of
      treatment the rats in all groups were sacrificed. The content of glutamate (Glu)
      and glycine (Gly) in brain tissues were determined and the pathological
      examination of brain tissues, hypophysis and sciatic nerve were conducted.
      RESULTS: The grip strength in 166.0 mg/m3 exposure group was significantly
      decreased (P < 0.05) compared with control group. The level of glutamate and
      glycine in female rats brain tissues was also significantly reduced (P < 0.05)
      after treatment with rich-d-transallethrin aerosol for 4 weeks. The result of
      pathological examination showed that cerebral cortex, hippocampus and cerebellum
      appeared neuron degeneration and slight axon swelling and myelin sheath
      destruction in sciatic nerve induced by 166.0 mg/m3 rich-d-transallethrin
      aerosol. CONCLUSION: The changes of Glu, Gly and pathological examination could
      be related to treatment with rich-d-transallethrin, in the meanwhile the major
      effect on nervous system appeared to be the cerebral cortex, hippocampal neuron
      and peripheral motor nerve.

PMID- 24868983
TI  - [Intervention effect of probiotic bifidobacterium on type 2 diabetes mellitus
      rats].
AB  - OBJECTIVE: To observe the influences of bifidobacterium on glucose and lipid
      metabolism and intestinal flora in type 2 diabetes mellitus rats. METHODS: Rats
      were randomly divided into 4 groups, the blank control group was fed with basic
      forage, the other 3 groups were fed with high fat diet. Meanwhile the high-dose
      and low-dose groups were gavage administrated with 12 and 4 ml/(kg x d) probiotic
      bifidobacterium for 6 weeks, then, injected with low dose of streptozotocin (20
      mg/kg). All rats were sacrificed 2 weeks later, blood and feces samples were
      collected to analyse. RESULTS: Compared with rats of type 2 diabetes model,
      glucose concentrations and serum concentrations of FFA, TG, LDL-C of 2
      experimental groups were significantly lower, serum concentrations of HDL-C were
      higher, insulin sensitivity index was higher, content of bifidobacterium was
      higher, but there were no significant differences in other 5 bacteria.
      CONCLUSION: The probiotic bifidobacterium could significantly ameliorate the
      disorder of glucose and lipid metabolism, increase the amount of bifidobacterium
      of type 2 diabetes rats.

PMID- 24868984
TI  - [Effect of curcumin on antioxidant function in the mice with acute alcoholic
      liver injury].
AB  - OBJECTIVE: To study the effect of curcumin on antioxidant function in the mice
      with acute alcoholic liver injury. METHODS: 50 male KM mices were randomly
      divided into 5 groups according to the weight, i. e. the normal control group,
      model control group, and curcumin low-dose group, middle-dose group, high-dose
      group (50, 100 and 200 mg/kg BW). After a 14-day administration, the relative
      liver weight, the content of MDA, the activity of SOD, GSH-Px, T-AOC in the liver
      tissue and the content of serum AST, ALT were determined. RESULTS: Compared with
      the normal control group, all indexes of model control group were significantly
      different (P < 0.05). The content of serum AST and ALT at high-dose group were
      significantly decreased compared with model control group (P < 0.05). Meanwhile,
      the activity of SOD, GSH-Px and T-AOC in the liver tissue were increased
      significantly (P < 0.05), and the content of MDA decreased significantly (P <
      0.05). CONCLUSION: Curcumin can improve the antioxidant activity of the mice with
      acute alcoholism, and has good protective effects on acute alcoholic liver injury
      in mice.

PMID- 24868985
TI  - [Experimental study on adsorption effect of activated carbon to abamectin].
AB  - OBJECTIVE: To investigate the adsorbability of activated charcoals for abamectin
      in vitro at various pH and concentrations. METHODS: Three concentrations of
      abamectin solutions (10, 5 and 2.5 g/L) with different pH value ( pH1.9 and
      pH6.8, respectively) were mixed with activated charcoal and control,
      respectively. The concentrations of abamectin were measured by UV-visible
      spectrophotometry after vibrated, incubated and centrifuged on different time
      points. Calculate the residue rate of abamectin and adsorption rate of activated
      carbon for avermectins. RESULTS: The abamectin was significantly decreased in
      activated charcoal group compared with control group and the absorption ability
      of activated charcoal was higher on low concentration of abamectin. CONCLUSION:
      In vitro experiment showed that activated charcoal can significantly adsorb
      abamectin.

PMID- 24868986
TI  - [Effect of salicylic acid on polysaccharide and microcystin contents in
      Microcystis aeruginosa PCC7806].
AB  - OBJECTIVE: To study the variation of polysaccharide (PS), which can be classified
      as capsule polysaccharide (EPS) and extracellular polysaccharide (EPS), and
      microcystin-RR (MC-RR) content of Microsystis aeruginosa under the stress of
      salicylic acid (SA). METHODS: 0, 0.25, 0.50, 0.75 and 1.00 mmol/L SA were added
      into the culture of M. aeruginosa at logarithmic phase and the contents of PS and
      MC-RR were quantified by phenol-sulfuric acid method and high performance liquid
      chromatography (HPLC) method in the 6th and 12th day. Meanwhile the effect of SA
      on PS and MC-RR contents were discussed at both the level of single cell and that
      of whole culture medium. RESULTS: CPS contents were increased with the increasing
      concentration of SA on the 6th day and decreases on the 12th day. The content of
      EPS and intracellular MC-RR first increases and then decreases with the
      increasing SA concentration in the whole stage. CONCLUSION: The contents of CPS
      and MC-RR increase for the stress of SA in early days, and then the contents of
      MC-RR both inside and outside the cell are decrease.

PMID- 24868987
TI  - [Simultaneous determination of 12 trace elements in children plasma sample by
      high resolution inductively coupled plasma mass spectrometry].
AB  - OBJECTIVE: To establish a method of determination of 12 trace elements (B, V, Cr,
      Mn, Fe, Co, Cu, Zn, Se, Rb, Sr, Mo) in children plasma for the fast,direct
      dilution by HR-ICP-MS. METHODS: The plasma samples were reconstituted,
      centrifuged for 15 minutes, then were added the internal elements of Ga and Y,
      diluted with 0.5% HNO3 by 1 : 20 (V/V). HR-ICP-MS was optimized and applied for
      the analysis. RESULTS: Detection limits were 0.001 - 0.035 microg/L, method
      detection limits of trace elements were 0.012 - 0.702 microg/L, coefficient of
      determination (R2) ranged from 0.9983 to 1. 0000 and the 3 levels of spiked
      recovery were between 85.86% and 121.34%, intra-day and inter-day precision were
      0.52% - 5.62% and 1.21% - 10.21%, as well as bovine serum certified samples
      further verified the accuracy. 12 trace elements in plasma of the children aged 3
      -12 years from poor rural in 2002 CNNHS, had been determined by Optimized HR-ICP
      MS. CONCLUSION: Preparation of plasma samples with 0.5% HNO3 combined with HR-ICP
      MS were applied for a large scale of sample analysis.

PMID- 24868988
TI  - The molecular biology of human iron metabolism.
AB  - Iron is one of the most important nonorganic substances that make life possible.
      Iron plays major roles in oxygen transport (eg, hemoglobin; -67% of total body
      iron [TBI]), short-term oxygen storage (eg, myoglobin; -3.5% of TBI), and energy
      generation (eg, cytochromes; -3% of TBI). Iron also serves vital roles in various
      nonheme-containing enzymes (-2% of TBI). Figure 1 lists heme-containing and
      nonheme iron-containing proteins. TBI is controlled by the rate of iron
      absorption; there are no physiologic mechanisms to excrete excess iron. Iron
      deficiency has many adverse consequences, including anemia, and in children,
      behavioral and learning disorders. Iron excess is toxic to the body, harming the
      heart, liver, skin, pancreatic islet beta cells, bones, joints, and pituitary
      gland. Maintaining proper iron balance is essential for maintaining homeostasis
      and health. TBI in adults normally ranges between 3.5 and 5.0 g. A total of 75%
      of TBI is functional, and 25% is stored within cells as ferritin or hemosiderin.
      Ferritin contains 24 subunits of light chains (L chains; 19.7 kDa) and heavy
      chains (H chains; 21.1 kDa). The L chains are encoded on chromosome 19q13.33 and
      are 175 amino acids long. The H chains are encoded on chromosome 11q1 and are 183
      amino acids long. Each ferritin molecule can contain as many as approximately
      4500 ferric ions. Because the major role of iron is in hemoglobin synthesis, this
      review will focus on iron, iron transport, and hematopoiesis.

PMID- 24868989
TI  - Cloning and expression of retinoic acid-induced gene-I and its effect on
      hepatitis C virus replication.
AB  - OBJECTIVE: To explore the influence of the retinoic acid indicible gene-I (RIG-I)
      on hepatitis C virus (HCV) replication and the molecular mechanism of action of
      RIG-I. METHODS: We constructed an RIG-I expression vector and co-transfected it
      into Huh-7 cells along with HCV-replicon RNA. We assayed HCV replication and NS5A
      protein synthesis via real-time polymerase chain reaction (RT-PCR) and western
      blotting. Also, we performed an enzyme-linked immunosorbent assay (ELISA) to
      measure the level of interferon (IFN)-alpha/-beta secretion. Additionally, we
      examined, via western blotting, the phosphorylation state of p38, Erk1/2, and
      nuclear factor (NF)-kappaB p65. RESULTS: Overexpression of RIG-1 in Huh-7 cells
      co-transfected with an HCV-replicon RNA significantly inhibited HCV replication
      and NS5A protein synthesis. Co-transfected cells had increased production of IFN
      alpha/-beta production and had higher levels of phosphorylated p38, Erk1/2, and
      NF-kappaB p65. CONCLUSIONS: RIG-I significantly inhibits HCV replication and NS5A
      protein synthesis by inducing type I IFN production. The underlying molecular
      mechanism for this effect appears to be mediated by increased phosphorylation of
      NF-kappaB p65, p38-mitogen-activated protein kinases (MAPK), and Erk1/2.

PMID- 24868990
TI  - The possible advantages of cryoprecipitate prepared from fresh frozen plasma from
      blood stored for 24 hours.
AB  - BACKGROUND: To compare the coagulation-factor profile of cryoprecipitate produced
      from fresh frozen plasma from whole blood (WB) stored for 24 hours at room
      temperature (24CP) with that of standard cryoprecipitate (CP). METHODS: We
      collected 80 units of WB from healthy volunteers, of which 20 units were of each
      blood group. Each unit of blood was divided into 2 parts. One part was used for
      preparation and quality-control evaluation of CP within 8 hours of collection;
      the other part was stored at room temperature for 24 hours and then subjected to
      CP preparation. Coagulation studies were carried out on each batch of CP after
      production. Fibrinogen, Factor VIII (FVII), and von Willibrand factor (vWF) were
      measured, and the blood groups were determined. We used the Student's t-test to
      perform comparisons and considered results to be significant at P < .005.
      RESULTS: Overall, all 3 clotting factors were increased in 24CP compared with CP,
      with a statistically significant increase in the level of FVIII. Blood group AB
      had significantly increased levels of fibrinogen and vWF in 24CP compared with
      CP. CONCLUSION: Our study showed that 24CP has equal or greater levels of
      coagulation factors compared with CP. His indicates that our alternate approach
      for preparation of CP may enable more efficient use of blood collected in
      satellite blood collection centers and during blood drives.

PMID- 24868991
TI  - Effects of lubricants and wash solutions on semen evaluation in a fertility
      clinic laboratory.
AB  - OBJECTIVE: The complex nature of semen components and the various collection
      procedures make standardization of semen analysis (SA) challenging. Therefore,
      the main goal of this study was to optimize and improve the quality and utility
      of the SA report. METHODS: Semen samples (n = 20) were split into 2 aliquots to
      compare 2 isolation gradients. Samples incubated in the different wash medium
      were evaluated for motility, forward progression, morphology, and suitability for
      intrauterine insemination (IUI). Another group (n = 20) was evaluated for IUI
      utility without and with a lubricant to compare motility and sperm count.
      RESULTS: There were no significant differences in motility, forward progression,
      or morphology with or without a lubricant. With respect to gradient types,
      PureSperm 40/80 isolated significantly higher yields of motile sperm than the
      isolate. In comparing wash media, at 2 hours PureSperm was significantly higher
      in both motility and count compared to Irvine culture media. CONCLUSION: This
      study represents a significant advance toward improved applications and methods
      for SA testing. Continued standardization and improvements in SA will require
      additional evaluation of lab testing methods.

PMID- 24868992
TI  - Prefixation of neutrophils for neutrophil antibody testing.
AB  - OBJECTIVE: The granulocyte immunofluorescence test based on flow cytometry is
      still the most commonly used method for detecting antineutrophil antibodies. We
      questioned whether neutrophil prefixation is necessary for this test. METHODS:
      Three pretreatment methods using paraformaldehyde were compared: unfixed, short
      fixed (3 minutes 40 seconds), and long-fixed (10 minutes) leukocytes. The mean
      fluorescence intensity (MFI) of a test sample was divided by the average of
      negative controls, and this MFI ratio of gated neutrophils or lymphocytes was
      assessed for its discriminatory value based on the pretreatment method used.
      RESULTS: In neutrophil antibody positive (Ab+) sera (n = 7), the MFI ratio of
      unfixed neutrophils (1.97) was higher than that of short- (1.60, P = 0.004) or
      long- (1.71, P = 0.203) fixed neutrophils. In HLA Ab+ sera (n = 10), the MFI
      ratio of short-fixed lymphocytes (8.85) was higher than that of unfixed (6.52, P
      = 0.120) or long-fixed (3.86, P = 0.055) lymphocytes. In antinuclear Ab+ sera (n
      = 4), the MFI ratio of unfixed neutrophils (2.04) was higher than that of short-
      (1.23, P = 0.047) or long- (1.14, P = 0.044) fixed neutrophils. CONCLUSION: The
      benefit of a prefixation step depends on the diagnostic purpose. Unfixed
      neutrophils are more sensitive, but the prefixed neutrophils are more specific.
      For the diagnosis of autoimmune neutropenia of childhood, prefixation can be
      omitted to enhance sensitivity.

PMID- 24868993
TI  - Hemolytic anemia and metastatic carcinoma: case report and literature review.
AB  - Hemolytic anemia can complicate the development of a variety of solid tumors and
      hematologic malignancies. Although patients may have an established diagnosis
      with documented metastases, microangiopathic hemolytic anemia (MAHA) can be a
      presenting feature of an occult malignancy. Prompt diagnosis is essential because
      conditions that mimic the symptoms of MAHA, including thrombotic thrombocytopenic
      purpura, have different prognoses and therapeutic options. Although the exact
      pathogenesis is not yet delineated, we present herein a case of cancer-associated
      MAHA and discuss the known pathways that can contribute to the initiation and
      propagation of hemolytic anemia in patients with cancer. The patient is a 69-year
      old woman with breast carcinoma that had metastasized to her rectum, urinary
      bladder, and brain. She eventually developed progressive decline in her
      functional status, with intermittent epistaxis and melena. The results of
      laboratory studies revealed hemolytic anemia and thrombocytopenia; results of a
      bone-marrow biopsy confirmed the involvement by metastatic carcinoma. The patient
      received red blood cell and platelet transfusions and was discharged to hospice
      care after clinical stabilization. She died soon thereafter.

PMID- 24868994
TI  - Primary body cavity-based large B-cell lymphoma in an HIV and HHV-8 negative, HCV
      positive patient: a case report and literature review.

PMID- 24868995
TI  - Fine needle aspiration of an unusual malignant mixed tumor in the parotid gland.
AB  - OBJECTIVE: The use of fine needle aspiration (FNA) biopsy in the triage of
      salivary gland tumors has been well established. The sensitivity and specificity
      of FNA biopsy for tumor diagnosis is generally very good. However, the diagnosis
      can be challenging due to the limited amount of tissue sampled, the occasional
      overlapping tumor morphology, and the presence of a malignant counterpart of a
      benign tumor. METHODS: FNA biopsy was performed with ultrasound guidance. Air
      dried slides and alcohol-fixed slides were made for Diff-Quik staining and
      Papanicolaou staining, respectively. The syringes were rinsed and a cell block
      was prepared. The resected specimen was fixed in 10% formalin and processed by
      routine histology techniques. RESULTS: We report a rare case of a salivary gland
      neoplasm with 2 distinct components: adenoid cystic carcinoma and pleomorphic
      adenoma. These 2 components are clearly identifiable in both cytological
      materials from fine needle aspiration and histological analysis of surgical
      resection. CONCLUSION: Pleomorphic adenoma is the most common salivary gland
      tumor for patients in all age groups. The characteristic cytological feature is
      fibrillary extracellular matrix intermixed with epithelial cells. Malignant
      transformation occurs in 5% to 10% of cases. Rarely, pleomorphic adenoma exists
      as one component of a hybrid tumor. The surgical resection will be needed in
      those cases. The final diagnosis relies on the combination of the clinical
      information, histological findings and molecular study.

PMID- 24868996
TI  - Hypercalcemic crisis due to vitamin D toxicity.

PMID- 24868997
TI  - Fine needle aspiration of a metastatic germ cell tumor to supraclavicular lymph
      node.
AB  - OBJECTIVE: Germ cell tumors are the most common tumors in men in their second
      decade. According to the National Comprehensive Cancer Network, the management of
      germ cell tumors depends on whether the tumor is diagnosed as a seminoma or a
      nonseminoma. Fine needle aspiration biopsy, compared to incisional biopsy, is
      relatively safe and facilitates rapid assessment of these tumors. METHODS: An
      ultrasound guided FNA biopsy was performed, and air-dried slides and alcohol
      fixed slides were made for Diff-Quik staining and Papanicolaou staining,
      respectively. The syringes were rinsed and cell block was prepared. The resected
      specimen was fixed in 10% formalin and processed by routine histology techniques.
      RESULTS: We report a case of a 22-year-old male with an enlarged scrotal mass and
      a supraclavicular nodule. A superficial fine needle aspiration biopsy was
      performed on the nodule and the correct diagnosis was made via cytomorphology and
      immunohistochemistry. The cytologic diagnosis was correlated with the incisional
      biopsy results. CONCLUSION: Fine needle aspiration biopsy is very helpful in the
      initial triage of germ cell tumors. When the aspirate contains sufficient
      diagnostic material, a specific diagnosis may be reached. Likewise, as different
      germ cell tumors have characteristic immunohistochemical profiles, a cell block
      from an aspirate may be critical for correct diagnosis. However, because germ
      cell tumors often contain mixed elements, cytologic diagnosis may not be entirely
      representative due to incomplete sampling. Thus, it is important to correlate
      cytologic diagnosis with the excisional tissue biopsy results.

PMID- 24868998
TI  - A rare case of chondroma of the parotid gland.

PMID- 24868999
TI  - Autoimmune hepatitis in a 20-year-old African American man.

PMID- 24869000
TI  - Blood collection from intravenous lines: is one drawing site better than others?
AB  - OBJECTIVE: Establish whether hemolysis in samples collected from intravenous
      lines is influenced by catheterization site. METHODS: Blood was collected from
      all patients (67 total) admitted to the emergency department the same morning,
      through a 20-gauge catheter placed in a vein of the upper limb directly into an
      evacuated blood tube. Serum was tested for hemolysis index by multi-wavelength
      photometric readings. RESULTS: The frequency of hemolyzed specimens was 30%
      (20/67). Hemolysis rate in median cephalic and basilic veins (17%) was comparable
      to that of median anterobrachial vein but lower than cephalic vein (29%; P =
      0.01), basilic vein (33%; P < 0.01), and metacarpal plexus veins (75%; P < 0.01).
      Compared with median basilic and cephalic veins, the relative risk of hemolysis
      was 1.4 from median anterobrachial vein, 1.6 from cephalic vein, 1.9 from basilic
      vein, and 4.3 from metacarpal plexus veins. CONCLUSION: Drawing blood from
      catheters placed distally from median veins carries higher hemolysis risk.

PMID- 24869001
TI  - Abbott ARCHITECT iPhenytoin assay versus similar assays for measuring free
      phenytoin concentrations.
AB  - OBJECTIVE: To measure free phenytoin (FP) concentrations in filtered specimens
      using the Abbott ARCHITECT iPhenytoin assay and to compare results from this
      method with results from the Abbott TDx/FLx assays. METHODS: We verified
      accuracy, analytic measurement range, and precision for FP measurements. For
      correlation and therapeutic interval studies, we used filtered calibrators,
      controls, proficiency-testing materials, and surplus clinical samples. After
      implementation, we determined proficiency testing results. RESULTS: The analytic
      measurement range was 2.0 to 25.0 micromol/L. Quality control materials (6.1,
      12.6, and 20.1 micromol/L) provided mean (SD) recoveries of 96.1 (5.0%), 99.2
      (5.0%), and 99.3 (5.7%), respectively, and coefficients of variation of 5.2%,
      5.0%, and 5.8%, respectively. Clinical specimens produced mean (SD) FP recovery
      levels of 103.7 (10.6%) (bias, 0.1 [0.3] micromol/L). Altering the FP therapeutic
      range (4.0-8.0 micromol/L) was unnecessary. Proficiency testing yielded
      consistently acceptable results. CONCLUSION: Our accuracy, precision, and
      correlation results were similar for the TDx/FLx and ARCHITECT assays, which
      demonstrates that the ARCHITECT iPhenytoin assay is acceptable for clinical FP
      measurements.

PMID- 24869419
TI  - Diffusion barrier and adhesion properties of SiO(x)N(y) and SiO(x) layers between
      Ag/polypyrrole composites and Si substrates.
AB  - This paper describes the interface reactions and diffusion between
      silver/polypyrrole (Ag/PPy) composite and silicon substrate. This composite
      material can be used as a novel technique for 3D-LSI (large-scale integration) by
      the fast infilling of through-silicon vias (TSV). By immersion of the silicon
      wafer with via holes into the dispersed solution of Ag/PPy composite, the holes
      are filled with the composite. It is important to develop a layer between the
      composite and the Si substrate with good diffusion barrier and adhesion
      characteristics. In this paper, SiOx and two types of SiOxNy barrier layers with
      various thicknesses were investigated. The interface structure between the Si
      substrate, the barrier, and the Ag/PPy composite was characterized by
      transmission electron microscopy. The adhesion and diffusion properties of the
      layers were established for Ag/PPy composite. Increasing thickness of SiOx proved
      to permit less Ag to transport into the Si substrate. SiOxNy barrier layers
      showed very good diffusion barrier characteristics; however, their adhesion
      depended strongly on their composition. A barrier layer composition with good
      adhesion and Ag barrier properties has been identified in this paper. These
      results are useful for filling conductive metal/polymer composites into TSV. 

PMID- 24869420
TI  - Determination of diffusion profiles in altered wellbore cement using X-ray
      computed tomography methods.
AB  - The development of accurate, predictive models for use in determining wellbore
      integrity requires detailed information about the chemical and mechanical changes
      occurring in hardened Portland cements. X-ray computed tomography (XRCT) provides
      a method that can nondestructively probe these changes in three dimensions. Here,
      we describe a method for extracting subvoxel mineralogical and chemical
      information from synchrotron XRCT images by combining advanced image segmentation
      with geochemical models of cement alteration. The method relies on determining
      "effective linear activity coefficients" (ELAC) for the white light source to
      generate calibration curves that relate the image grayscales to material
      composition. The resulting data set supports the modeling of cement alteration by
      CO2-rich brine with discrete increases in calcium concentration at reaction
      boundaries. The results of these XRCT analyses can be used to further improve
      coupled geochemical and mechanical models of cement alteration in the wellbore
      environment. 

PMID- 24869423
TI  - Bulk heterojunction solar cells: morphology and performance relationships.

PMID- 24869425
TI  - Diastereoselective three-component vinylogous Mannich reaction of nitrogen
      heterocycles, acyl/sulfonyl chlorides, and silyloxyfurans/pyrroles.
AB  - A one-step, 3-component vinylogous Mannich reaction of trimethylsilyloxyfuran or
      N-protected tert-butyldimethylsilyloxypyrrole with a variety of nitrogen
      containing heterocycles in the presence of diverse electrophiles is described.
      The reaction products were generally obtained in high yields and as a single
      diastereoisomer having the (R*,R*) relative configuration based on
      crystallographic studies of several derivatives. Several azaheterocycles were
      successfully used for this reaction, such as isoquinolines, quinoline,
      phenanthridine, quinazoline, phthalazine, and beta-carboline, and electrophiles
      included acetyl chloride, methyl chloroformate, methyl chloromalonate, 2
      bromobutanoyl chloride, and arylsulfonyl chlorides. The products of the
      vinylogous Mannich reactions were subjected to further transformations, leading
      to highly functionalized and stereochemically defined tetracyclic derivatives
      that are valuable building blocks for the preparation of natural products or
      medicinal agents. 

PMID- 24869428
TI  - Iranian and English women's use of religion and spirituality as resources for
      coping with infertility.
AB  - The study reported in this paper explores how infertile women cope with
      infertility using their religious and spiritual beliefs. In total, 30 infertile
      women affiliated to different denominations of Christianity and Islam were
      interviewed in the UK and Iranian fertility clinics using grounded theory. The
      categories which emerged included governing ones' 'Self' through gaining control
      of emotions, adopting religious coping strategies, and handling the burden of
      infertility peacefully, which all related to the core category of 'relying on a
      higher being'. We argue that infertile women employ a variety of religious and
      spiritual coping strategies which are associated with adaptive health outcomes.
      Further scientific inquiry is required to investigate how religion and
      spirituality promote adaptation to infertility.

PMID- 24869429
TI  - 11th European Symposium on Pediatric Cochlear Implantation (ESPCI).

PMID- 24869430
TI  - An image-guided robot system for direct cochlear access.
AB  - The aim of direct cochlear access (DCA) is to replace the standard mastoidectomy
      with a small diameter tunnel from the lateral bone surface to the cochlea for
      electrode array insertion. In contrast to previous attempts, the approach
      described in this work not only achieves an unprecedented high accuracy, but also
      contains several safety sub-systems. This paper provides a brief description of
      the system components, and summarizes accuracy results using the system in a
      cadaver model over the past two years. 

PMID- 24869427
TI  - Activation of the phase II enzymes for neuroprotection by ginger active
      constituent 6-dehydrogingerdione in PC12 cells.
AB  - The cellular endogenous antioxidant system plays pivotal roles in counteracting
      or retarding the pathogenesis of many neurodegenerative diseases. Molecules with
      the ability to enhance the antioxidant defense thus are promising candidates for
      neuroprotective drugs. 6-Dehydrogingerdione (6-DG), one of the major components
      of dietary ginger, has received increasing attention due to its multiple
      pharmacological activities. However, how this pleiotropic molecule works on the
      neuronal system has not been studied. This paper reports that 6-DG efficiently
      scavenges various free radicals in vitro and displays remarkable cytoprotection
      against oxidative stress-induced neuronal cell damage in the neuron-like rat
      pheochromocytoma cell line, PC12 cells. Pretreatment of PC12 cells with 6-DG
      significantly up-regulates a panel of phase II genes as well as the corresponding
      gene products, such as glutathione, heme oxygenase, NAD(P)H: quinone
      oxidoreductase, and thioredoxin reductase. Mechanistic study indicates that
      activation of the Keap1-Nrf2-ARE pathway is the molecular basis for the
      cytoprotection of 6-DG. This is the first revelation of this novel mechanism of 6
      DG as an Nrf2 activator against oxidative injury, providing the potential
      therapeutic use of 6-DG as neuroprotective agent.

PMID- 24869431
TI  - Comparisons of the pitch perception abilities of adults and children using
      cochlear implants or hearing aids.

PMID- 24869432
TI  - Electric-acoustic stimulation in adults: localization and speech perception.
AB  - This paper reports findings from a study that was aimed at investigating how best
      to prescribe devices that provide electric-acoustic stimulation. The localization
      and speech perception of adults who use electric-acoustic stimulation in one ear
      and acoustic amplification in the opposite ear were evaluated. Results indicated
      localization benefits when acoustic amplification was used in both ears.
      Systematic adjustments of the relative output and cross-over frequencies were
      implemented to determine the settings that optimized outcomes. Results from a
      case study indicated benefits for localization and speech perception when
      electric-acoustic stimulation in one ear was combined with a hearing aid in the
      opposite ear, after acoustic-to-electric levels and cross-over frequencies were
      optimized. 

PMID- 24869434
TI  - Long-term results of partial deafness treatment.
AB  - Treatment of the partial deafness is a great challenge in terms of preserving the
      preoperative hearing and complementing this hearing ability with an implant. It
      concerns the situations when hearing in low frequency range is normal or fully
      functional and it is only necessary to complement it electrically in the medium
      and high frequency ranges. The first in the world surgery during which an
      existing normal hearing had been electrically complemented was performed in 2002.
      It has shown a fresh direction in treatment of various partial hearing
      impairments. This achievement was possible due to our previous works on hearing
      preservation in the group of patients with marginal residual hearing. The long
      term observation (almost 15 years) and large material allow us to present the
      strategy of the partial deafness treatment and its results. During the ESPCI
      conference in Warsaw in 2009, PDT concept was announced, indicating groups for
      Acoustic Stimulation (AS) and Electric Stimulation (ES). ES patients can be
      divided on the following groups: Electrical Complement (PDT-EC), Electric
      Acoustic Stimulation (PDT-EAS), Electric Modified Stimulation (PDT-EMS), Electric
      Stimulation (PDT-ES). The differentiation between the groups is very important,
      because the groups are not equal and their goals in treatment and therapy are
      different. Concluding we can say that hearing was preserved in over 94% of cases,
      however, the results differ between the groups. Implementation of the partial
      deafness treatment (PDT) is connected with development and elaboration of special
      rehabilitation program for the specific groups of patients. 

PMID- 24869435
TI  - Results of SRA Nucleus Freedom CI in population of children with functional
      residual hearing.

PMID- 24869436
TI  - Phonological awareness and early reading skills in children with cochlear
      implants.
AB  - This paper summarizes findings from a population study on outcomes of children
      with hearing loss in Australia, the Longitudinal Outcomes of Children with
      Hearing Impairment ( http://www.outcomes.nal.gov.au ) study. Children were
      evaluated at several intervals using standardized tests, and the relationship
      between a range of predictors and the outcomes was examined. This paper reports
      the performance of children with cochlear implants at 5 years of age together
      with factors predicting word reading ability. Earlier age at cochlear
      implantation was significantly associated with better word reading ability, after
      controlling for the effects of language, receptive vocabulary, nonverbal
      cognitive ability, and device configuration. 

PMID- 24869437
TI  - European young people with cochlear implants: developing confidence and
      communication.

PMID- 24869438
TI  - Age at implantation and auditory memory in cochlear implanted children.
AB  - Early cochlear implantation, before the age of 3 years, provides the best outcome
      regarding listening, speech, cognition an memory due to maximal central nervous
      system plasticity. Intensive postoperative training improves not only auditory
      performance and language, but affects auditory memory as well. The aim of this
      study was to discover if the age at implantation affects auditory memory function
      in cochlear implanted children. A total of 50 cochlear implanted children aged 4
      to 8 years were enrolled in this study: early implanted (1-3y) n = 27 and late
      implanted (4-6y) n = 23. Two types of memory tests were used: Immediate Verbal
      Memory Test and Forward and Backward Digit Span Test. Early implanted children
      performed better on both verbal and numeric tasks of auditory memory. The
      difference was statistically significant, especially on the complex tasks. Early
      cochlear implantation, before the age of 3 years, significantly improve auditory
      memory and contribute to better cognitive and education outcomes. 

PMID- 24869439
TI  - LEAPing on with language: An on-line language programme to support classroom
      teachers and parents of primary school children (aged 5-11 years).
AB  - The Leaping on with Language programme provides a combination of strategies and
      activities to accelerate children's spoken language use from simple sentences to
      complex language. Using a conversational philosophy it expands the building
      blocks of language (vocabulary, grammar, speech), whilst emphasising the
      importance of developing independent social communication and acknowledging a
      child's developing self esteem and self identity between the ages of 4-11. Three
      pilot projects evaluated the programme with a total of 51 delegates. The outcomes
      were hugely positive. Changes in behaviour were reported from the 3rd pilot 1
      month later. Comments regarding the length of training, practical strategies and
      more film clips were implemented. Leaping on with language is now a free to
      access resource available on line. 

PMID- 24869440
TI  - LittlEARS((r)) early speech production questionnaire validation in hearing
      Turkish infants.
AB  - AIM: The LEESPQ validated on hearing, German infants is a standardized tool
      examining preverbal speech development. This study aims to validate the LEESPQ on
      hearing, Turkish infants. MATERIALS AND METHODS: This is a prospective, cross
      sectional validation study using the LEESPQ in Turkish. The LEESPQ was filled in
      once for each hearing infant. Data for >=10 infants was collected at 19 test
      intervals, >= 0-1, >= 1-2......, >=18-19 months. Psychometric validation was
      performed through confirmatory factor analysis, item response analysis, item
      analysis, and analysis of reliability and validity. RESULTS: The LEESPQ was found
      to be gender independent, have high predictive accuracy and almost exclusively
      assess speech production ability. A very high correlation between total score and
      chronological age means score can be interpreted as child's speech production
      developmental age. Expected and minimum scores were defined for each monthly
      interval. CONCLUSION: The LEESPQ (Turkish) has clinical value to confirm typical
      speech production development and detect potential problems.

PMID- 24869441
TI  - Deep insertion - round window approach by using SRA electrode.
AB  - Hearing preservation surgery requires specially a traumatic technique. Having
      some preoperative anatomical data of the size of patient's cochlea surgeon can
      design his or her insertion depth. In the study we have evaluated a relation
      between hearing preservation rate and angular insertion depth estimated
      intraoperatively and postoperatively having measured insertion angle from
      radiological assessment and calculations given by Escude. There has not been no
      statistically significant difference between insertion depth angle, either
      estimated intraoperatively and measured and calculated post-operatively, and
      hearing preservation rate in the group. This analysis confirms a traumaticy of
      insertion in hearing preservation surgery. 

PMID- 24869442
TI  - Language and speech perception of young children with bimodal fitting or
      bilateral cochlear implants.
AB  - OBJECTIVES: This paper compares language development and speech perception of
      children with bimodal fitting (a cochlear implant in one ear and a hearing aid in
      the opposite ear) or bilateral cochlear implantation. METHODS: Participants were
      children enrolled in the Longitudinal Outcomes of Children with Hearing
      Impairment study. Language development was assessed at 3 years of age using
      standardized tests. Speech perception was evaluated at 5 years of age. Speech was
      presented from a frontal loudspeaker, and babble noise was presented either from
      the front or from both sides. RESULTS: On average, there was no significant
      difference in language outcomes between 44 children with bimodal fitting and 49
      children with bilateral cochlear implants; after controlling for a range of
      demographic variables. Earlier age at cochlear implant activation was associated
      with better outcomes. Speech perception in noise was not significantly different
      between children with bimodal fitting and those with bilateral cochlear implants.
      Compared to normal-hearing children, children with cochlear implants required a
      better signal-to-noise ratio to perform at the same level, but demonstrated
      spatial release from masking of a similar magnitude. CONCLUSIONS: This population
      based study found that language scores for children with bilateral implants were
      higher than those with bimodal fitting or those with unilateral implants, but
      neither reached significance level.

PMID- 24869443
TI  - Is complex signal processing for bone conduction hearing aids useful?
AB  - OBJECTIVES: To establish whether complex signal processing is beneficial for
      users of bone anchored hearing aids. METHODS: Review and analysis of two studies
      from our own group, each comparing a speech processor with basic digital signal
      processing (either Baha Divino or Baha Intenso) and a processor with complex
      digital signal processing (either Baha BP100 or Baha BP110 power). The main
      differences between basic and complex signal processing are the number of
      audiologist accessible frequency channels and the availability and complexity of
      the directional multi-microphone noise reduction and loudness compression
      systems. RESULTS: Both studies show a small, statistically non-significant
      improvement of speech understanding in quiet with the complex digital signal
      processing. The average improvement for speech in noise is +0.9 dB, if speech and
      noise are emitted both from the front of the listener. If noise is emitted from
      the rear and speech from the front of the listener, the advantage of the devices
      with complex digital signal processing as opposed to those with basic signal
      processing increases, on average, to +3.2 dB (range +2.3 ... +5.1 dB, p <=
      0.0032). DISCUSSION: Complex digital signal processing does indeed improve speech
      understanding, especially in noise coming from the rear. This finding has been
      supported by another study, which has been published recently by a different
      research group. CONCLUSIONS: When compared to basic digital signal processing,
      complex digital signal processing can increase speech understanding of users of
      bone anchored hearing aids. The benefit is most significant for speech
      understanding in noise.

PMID- 24869444
TI  - Cochlear implantation in children with auditory neuropathy spectrum disorders.
AB  - AIM: To present the outcomes of cochlear implantation (CI) in children with
      auditory neuropathy spectrum disorders (ANSD). MATERIALS AND METHODS: The pre-
      and post-CI hearing outcomes in children with ANSD were retrospectively
      evaluated. Performance was assessed with categories of auditory performance (CAP)
      and the Manchester spoken language development scale (MSLDS). RESULTS: Full data
      were available in 27 implanted children with ANSD with average age at
      implantation 35.4 months (range 19-68 months). Nine children were implanted
      bilaterally, while 13 were bimodal. The pre-CI CAP and MSLDS scores were 2.5
      (range 0-5) and 2.5 (range 0-6), while the post-CI scores 5.8 (range 2-9) and 7.7
      (range 3-10), respectively. CONCLUSIONS: Although the outcome of CI in children
      with ANSD might vary, it is favourable in most of the cases. CI seems a justified
      hearing rehabilitation option for children with ANSD and limited benefits from
      conventional hearing aids.

PMID- 24869445
TI  - Cross-modal perception of rhythm in music and dance by cochlear implant users.
AB  - Two studies examined adult cochlear implant (CI) users' ability to match auditory
      rhythms occurring in music to visual rhythms occurring in dance (Cha Cha, Slow
      Swing, Tango and Jive). In Experiment 1, adults CI users (n = 10) and hearing
      controls matched a music excerpt to choreographed dance sequences presented as
      silent videos. In Experiment 2, participants matched a silent video of a dance
      sequence to music excerpts. CI users were successful in detecting timing
      congruencies across music and dance at well above-chance levels suggesting that
      they were able to process distinctive auditory and visual rhythm patterns that
      characterized each style. However, they were better able to detect cross-modal
      timing congruencies when the reference was an auditory rhythm than when the
      reference was a visual rhythm. Learning strategies that encourage cross-modal
      learning of musical rhythms may have applications in developing novel
      rehabilitative strategies to enhance music perception and appreciation outcomes
      of child implant users. 

PMID- 24869446
TI  - Cochlear's unique electrode portfolio now and in the future.
AB  - OBJECTIVES: To review Cochlear's electrode portfolio and discuss the merits of
      current and future straight and perimodiolar electrode arrays. To present an
      update on implant reliability. METHODS: Performance and hearing preservation data
      from studies involving the Slim Straight (CI422), Hybrid L24 and Contour Advance
      electrode array were reviewed. RESULTS: While several studies in past found
      little difference in performance outcomes between subjects implanted with
      perimodiolar and straight arrays, recent studies demonstrated that proximity to
      the modiolus is correlated with better performance. Hearing threshold increase
      was lowest with the Hybrid L24, closely followed by the slim straight array and
      was largest with the Contour Advance array. The CI24RE receiver-stimulator used
      for the three arrays had a cumulative survival of 99% at eight years post
      implantation. CONCLUSIONS: Combining the hearing preservation benefits of slim
      straight arrays with perimodiolar proximity is the design objective of Cochlear's
      next generation electrodes.

PMID- 24869447
TI  - First functional rehabilitation via vestibular implants.

PMID- 24869448
TI  - Evaluation of cost-utility in middle ear implantation in the 'Nordic School': a
      multicenter study in Sweden and Norway.

PMID- 24869449
TI  - Neuroelectrical imaging study of music perception by children with unilateral and
      bilateral cochlear implants.
AB  - OBJECTIVE: To investigate by means of non-invasive neuroelectrical imaging the
      differences in the perceived pleasantness of music between children with cochlear
      implants (CI) and normal-hearing (NH) children. METHODS: 5 NH children and 5
      children who received a sequential bilateral CI were assessed by means of High
      Resolution EEG with Source Reconstruction as they watched a musical cartoon.
      Implanted children were tested before and after the second implant. For each
      subject the scalp Power Spectral Density was calculated in order to investigate
      the EEG alpha asymmetry. RESULTS: The scalp topographic distribution of the EEG
      power spectrum in the alpha band was different in children using one CI as
      compared to NH children (see figure). With two CIs the cortical activation
      pattern changed significantly, becoming more similar to the one observed in NH
      children. CONCLUSIONS: The findings support the hypothesis that bilateral CI
      users have a closer-to-normal perception of the pleasantness of music than
      unilaterally implanted children.

PMID- 24869450
TI  - A computed tomographic data-based vibrant bonebridge visualization tool.
AB  - AIM: Information about the temporal bone size and variations of anatomical
      structures are crucial for a safe positioning of the Vibrant Bonebridge B-FMT. A
      radiological based preoperative planning of the surgical procedure decreases the
      surgical time and minimizes the risk of complications. MATERIALS AND METHODS: We
      developed a software tool, which allows a catch up of foreign DICOM data based CT
      temporal bone scans. The individual CT scan is transmitted into a 3D
      reconstructed pattern of the temporal bone. In this 3D reconstruction the
      individually favored position of the B- FMT should be found. RESULTS: The
      software allows a determination of a safe B-FMT position by identifying the
      individual relation of middle fossa, jugular bulb and external auditory canal.
      Skull thickness and screw length are contained parameters for the surgical
      planning. CONCLUSION: An easy to handle software tool allows a radiologically
      data based safe and fast surgical positioning of the B-FMT.

PMID- 24869451
TI  - Impact of auditory cortical asymmetry in cochlear implantation.
AB  - OBJECTIVE: Is there a cochlear implant ear advantage for speech perception?
      Patients A total number of 68 cochlear implant recipients were evaluated
      retrospectively. They were 20 adults implanted in right ear, 20 matched adults
      implanted in left ear while 14 children implanted in right ear and 14 matched
      children implanted in left ear. METHODS: Behavioral responses & age based speech
      perception tests were evaluated at 6 months and 1 year post implantation.
      RESULTS: Adult showed no statistical difference in all tests at 6 months
      evaluation while 1 year evaluation showed significant better performance for
      right implanted group in monosyllabic discrimination test. Children showed
      statistical significant performance in monosyllabic identification and minimal
      pairs testes at 6 months evaluation; and in monosyllabic identification only at 1
      year evaluation. CONCLUSION: The present data support that right ear implantation
      would fasten the development of auditory skills especially in young children, an
      issue to be considered in unilateral implantation.

PMID- 24869452
TI  - FS4 for partial deafness treatment.

PMID- 24869453
TI  - Does cochleostomy location influence electrode trajectory and intracochlear
      trauma?

PMID- 24869454
TI  - The importance of matrix metalloproteinase-3 in respiratory disorders.
AB  - The matrix metalloproteinases (MMPs) encompass a family of zinc-dependent
      endopeptidases that are secreted into the extracellular environment or remain
      bound to the cell surface. While MMPs were initially identified based on their
      ability to degrade collagen and other components of the extracellular matrix,
      recent studies indicate that their non-degradative functions are physiologically
      paramount. In particular, MMPs are now known to participate in diverse
      physiological processes that control key aspects of inflammatory and immune
      responses and neoplasia, in part by selective triggering of cellular signaling
      pathways via limited proteolytic processing of extracellular and membrane
      associated proteins, including cytokines and cell surface receptors. Herein, we
      focus on the unique roles of MMP-3 (stromelysin-1) in acute lung injury and
      repair, pulmonary fibrosis, and lung cancer. 

PMID- 24869455
TI  - Paradigms of public policies for licit and illicit drugs in Brazil.
AB  - Brazil is a country of continental dimensions that, over the last 3 decades, has
      been making increased efforts to develop effective public policies for
      controlling the use of both licit and illicit psychoactive substances. In the
      case of licit drugs, Brazil was a pioneer in following the guidance of the World
      Health Organization for tobacco control and has witnessed surprising results
      relating to reduction of smoking prevalence and correlated morbidity and
      mortality. Today, Brazil has a national structure for organizing, applying, and
      monitoring laws relating to tobacco. However, in the field of illicit drugs, with
      crack consumption as a paradigm, the situation is the opposite: its use has been
      increasing year by year and is being consumed at increasingly young ages and by
      all social classes. Thus, it is becoming an enormous challenge for public
      policies relating to prevention and treatment. In this context, the aim of this
      article is to present a review of the epidemiological data relating to tobacco
      and crack use in Brazil, with an analysis on the impact of public policies for
      controlling consumption over recent years. Despite the efforts made over the last
      3 decades, Brazil still has a long way to go in order to construct a consistent
      and effective national drugs policy.

PMID- 24869459
TI  - One-step synthesis of xanthones catalyzed by a highly efficient copper-based
      magnetically recoverable nanocatalyst.
AB  - A versatile and highly efficient strategy to construct a xanthone skeleton via a
      ligand-free intermolecular catalytic coupling of 2-substituted benzaldehydes and
      a wide range of phenols has been developed. For this purpose, a novel and
      magnetically recoverable catalyst consisting of copper nanoparticles on nanosized
      silica coated maghemite is presented. The reaction proceeds smoothly with easy
      recovery and reuse of the catalyst. The methodology is compatible with various
      functional groups and provides an attractive protocol for the generation of a
      small library of xanthones in very good yield. 

PMID- 24869464
TI  - Reading pulmonary vascular pressure tracings. How to handle the problems of zero
      leveling and respiratory swings.
AB  - The accuracy of pulmonary vascular pressure measurements is of great diagnostic
      and prognostic relevance. However, there is variability of zero leveling
      procedures, and the current recommendation of end-expiratory reading may not
      always be adequate. A review of physiological and anatomical data, supported by
      recent imaging, leads to the practical recommendation of zero leveling at the
      cross-section of three transthoracic planes, which are, respectively midchest
      frontal, transverse through the fourth intercostal space, and midsagittal. As for
      the inevitable respiratory pressure swings, end-expiratory reading at functional
      residual capacity allows for minimal influence of elastic lung recoil on
      pulmonary pressure reading. However, hyperventilation is associated with changes
      in end-expiratory lung volume and increased intrathoracic pressure, eventually
      exacerbated by expiratory muscle contraction and dynamic hyperinflation, all
      increasing pulmonary vascular pressures. This problem is amplified in patients
      with obstructed airways. With the exception of dynamic hyperinflation states, it
      is reasonable to assume that negative inspiratory and positive expiratory
      intrathoracic pressures cancel each other out, so averaging pulmonary vascular
      pressures over several respiratory cycles is most often preferable. This
      recommendation may be generalized for the purpose of consistency and makes sense,
      as pulmonary blood flow measurements are not corrected for phasic inspiratory and
      expiratory changes in clinical practice. 

PMID- 24869461
TI  - Use of ulipristal acetate and levonorgestrel for emergency contraception: a
      follow-up study.
AB  - OBJECTIVES: Previously we showed that increasing the choice of emergency
      contraception (EC) guided by medical eligibility did not result in wholesale
      large-scale usage of ulipristal acetate (UPA). This further 12-month study aimed
      to answer three questions. (1) Does offering choice of EC lead to change in
      methods used? (2) Are women who choose UPA more likely than those who choose
      levonorgestrel (LNG) to continue using condoms for subsequent contraception or to
      decline any ongoing contraception? (3) Do more women choosing LNG 'quick start'
      hormonal contraception? METHODS: A retrospective study of EC episodes (1 April
      2012 to 31 March 2013) by quarters. Among women offered all three methods of EC
      (49.1%) we noted the method chosen, and decisions on ongoing contraception among
      those choosing either LNG or UPA. Differences were tested for statistical
      significance. RESULTS: In 6110 episodes of EC, LNG was issued in 69.2%, UPA in
      26.0%, and a copper intrauterine device (Cu-IUD) was fitted in 4.8%. Quarter by
      quarter, the data show a small decline in LNG use, suggesting plateauing by the
      last quarter, and a significant increase in UPA use between the first and the
      other three quarters (p<0.001). Use of the Cu-IUD remained static. The percentage
      of women offered three methods rose to 54.2%. In women offered full choice (3000;
      49.1%) we saw a significant increase in choice of UPA, from 39.3% to 48.6%
      (p<0.001). Women who chose LNG were more likely to quick start (p=0.02) or be
      continuing contraception already used (p<0.001). Overall, those choosing UPA were
      more likely to use condoms (p<0.001) but were no more likely to decline ongoing
      contraception (p=0.13). CONCLUSIONS: There was a significant increase in women
      using UPA for EC compared with our previous study, particularly among those
      wishing to use condoms for continuing contraception. Women choosing LNG were more
      likely to quick start pills or to continue current hormonal contraception.
      Detailed attention to continuing contraception following EC may be an important
      factor in the prevention of unwanted pregnancy.

PMID- 24869465
TI  - Design and execution of clinical trials in orthopaedic surgery.
AB  - High-quality randomised controlled trials (RCTs) evaluating surgical therapies
      are fundamental to the delivery of evidence-based orthopaedics. Orthopaedic
      clinical trials have unique challenges; however, when these challenges are
      overcome, evidence from trials can be definitive in its impact on surgical
      practice. In this review, we highlight several issues that pose potential
      challenges to orthopaedic investigators aiming to perform surgical randomised
      controlled trials. We begin with a discussion on trial design issues, including
      the ethics of sham surgery, the importance of sample size, the need for patient
      important outcomes, and overcoming expertise bias. We then explore features
      surrounding the execution of surgical randomised trials, including ethics review
      boards, the importance of organisational frameworks, and obtaining adequate
      funding. Cite this article: Bone Joint Res 2014;3:161-8. 

PMID- 24869466
TI  - Clinical trial networks in orthopaedic surgery.
AB  - The aim of this study was to review the role of clinical trial networks in
      orthopaedic surgery. A total of two electronic databases (MEDLINE and EMBASE)
      were searched from inception to September 2013 with no language restrictions.
      Articles related to randomised controlled trials (RCTs), research networks and
      orthopaedic research, were identified and reviewed. The usefulness of trainee-led
      research collaborations is reported and our knowledge of current clinical trial
      infrastructure further supplements the review. Searching yielded 818 titles and
      abstracts, of which 12 were suitable for this review. Results are summarised and
      presented narratively under the following headings: 1) identifying clinically
      relevant research questions; 2) education and training; 3) conduct of multicentre
      RCTs and 4) dissemination and adoption of trial results. This review confirms
      growing international awareness of the important role research networks play in
      supporting trials in orthopaedic surgery. Multidisciplinary collaboration and
      adequate investment in trial infrastructure are crucial for successful delivery
      of RCTs. Cite this article: Bone Joint Res 2014;3:169-74. 

PMID- 24869467
TI  - Nocturnal systemic hypotension increases the risk of glaucoma progression.
AB  - OBJECTIVE: The objective of this prospective, longitudinal study of patients with
      normal-tension glaucoma (NTG) was to determine whether patients with nocturnal
      hypotension are at greater risk for visual field (VF) loss over 12 months than
      those without nocturnal hypotension. DESIGN: Prospective, longitudinal study.
      PARTICIPANTS: Consecutive patients with NTG with at least 5 prior VF tests were
      screened for eligibility. METHODS: The baseline evaluation assessed demographic
      and clinical characteristics, covering systemic comorbid conditions, including
      systemic hypertension. All oral and ophthalmologic medications were recorded. A
      complete ophthalmological examination was performed at baseline and follow-up.
      Patients had their blood pressure (BP) monitored every 30 minutes for 48 hours
      with an ambulatory recording device at baseline and 6 and 12 months. MAIN OUTCOME
      MEASURES: The primary outcome was based on the global rates of VF progression by
      linear regression of the mean VF threshold sensitivity over time (decibels/year).
      RESULTS: Eighty-five patients with NTG (166 eyes; mean age, 65 years; 67% were
      women) were included. Of the 85 patients, 29% had progressed in the 5 VFs
      collected before study enrollment. The nocturnal mean arterial pressure (MAP) was
      compared with the daytime MAP. Multivariate analysis showed that the total time
      that sleep MAP was 10 mmHg below the daytime MAP was a significant predictor of
      subsequent VF progression (P<0.02). CONCLUSIONS: Cumulative nocturnal hypotension
      predicted VF loss in this cohort. Our data suggest that the duration and
      magnitude of decrease in nocturnal blood pressure below the daytime MAP,
      especially pressures that are 10 mmHg lower than daytime MAP, predict progression
      of NTG. Low nocturnal blood pressure, whether occurring spontaneously or as a
      result of medications, may lead to worsening of VF defects.

PMID- 24869471
TI  - Anxieties of communication: the limits of narrative in the medical humanities.
AB  - This paper aims to provide an initial response to Angela Woods's endeavour to
      '(re)ignite critical debates around this topic' in her recent essay 'The limits
      of narrative: provocations for the medical humanities' (Medical Humanities 2011).
      Woods's essay challenges the validity of the notion of the narrative self through
      her discussion and use of Galen Strawson's seminal 'Against narrativity' (2004).
      To some extent in dialogue with Woods, this article will examine three
      exploratory concepts connected with the topic. First, it will explore ways in
      which we might seek to re-place narrative at the centre of the philosophy of good
      medicine and medical practice by reassessing the role of the narratee in the
      narrative process. Second, it will reconsider the three alternative forms of
      expression Woods puts forward as non-narrative--metaphor, phenomenology and
      photography--as narrative. Finally, and connected to the first two areas of
      discussion, it will reflect on ways in which narrative might be used to interpret
      illness and suffering in medical humanities contexts. What I hope to show, in
      relation to Woods's work on this subject, is that in order to be interpreted
      (indeed interpretable) the types of non-narrative representation and
      communication she discusses in fact require a narrative response. We employ
      narratology to engage with illness experience because narrative is so fundamental
      to meaning-making that it is not just required, it is an inherent human response
      to creative outputs we encounter. This is a quite different approach to the
      question of narrativity in the medical humanities, and it is therefore related
      to, but not entirely hinged upon, the work that Woods has done, but it is
      intended to spark further discussion across the emergent discipline.

PMID- 24869475
TI  - Visualizing individual carbon nanotubes with optical microscopy.
AB  - This paper reports a high-throughput, label-free technique to visualize
      individual carbon nanotubes (CNTs) on a silicon wafer using a conventional
      optical microscope. We show that individual CNTs can locally enhance the rate of
      vapor-phase HF etching of SiO2 to produce a SiO2 trench that is several to
      several tens of nanometers in depth. The trench is visible under an optical
      microscope due to a change in the optical interference in the SiO2 layer,
      allowing the location of an individual CNT to be determined. With this technique,
      we demonstrate high-throughput Raman characterization and reactivity studies on
      individual CNTs. 

PMID- 24869470
TI  - Genotyping of Yersinia enterocolitica biotype 1A strains from clinical and
      nonclinical origins by pulsed-field gel electrophoresis.
AB  - Yersinia enterocolitica biotype 1A (B1A) strains are considered mainly
      nonpathogenic. However, some studies considered strains of this biotype to be the
      causal agents of infections in humans and animals. In South America, there are no
      studies that have compared clinical and nonclinical strains of B1A typed by
      pulsed-field gel electrophoresis (PFGE) and none that have compared the
      capability of different enzymes on typing these strains. This study typed 51 Y.
      enterocolitica B1A strains isolated in Brazil and Chile by PFGE, testing the
      enzymes XbaI, NotI, and XhoI. The resulting dendrograms discriminated the strains
      in 47, 40, and 49 pulsotypes generated by the cleavage with the enzymes XbaI,
      NotI, and XhoI, respectively. The majority of the strains were grouped
      independently of their clinical or nonclinical origins. The high discriminatory
      power of PFGE confirmed the heterogeneity of B1A strains but could not divide the
      strains studied into clusters that differed in the frequency of some virulence
      genes as observed in studies using other methodologies. 

PMID- 24869477
TI  - Transfer of pre-assembled block copolymer thin film to nanopattern unconventional
      substrates.
AB  - In this work, we demonstrate that a preassembled block copolymer (BCP) thin film
      can be floated, transferred, and utilized to effectively nanopattern
      unconventional substrates. As target substrates, we chose Cu foil and graphene/Cu
      foil since they cannot be nanopatterned via conventional processes due to the
      high surface roughness and susceptibility to harsh processing chemicals and
      etchants. Perpendicular hexagonal PMMA cylinder arrays in diblock copolymer
      poly(styrene-block-methyl methacrylate) [P(S-b-MMA)] thin films were preassembled
      on sacrificial SiO2/Si substrates. The BCP thin film was floated at the air/water
      interface off of a SiO2/Si substrate and then collected with the target
      substrate, leading to well-defined nanoporous PS templates on these uneven
      surfaces. We further show that the nanoporous template can be used for a
      subtractive process to fabricate nanoperforated graphene on Cu foil in sub-20 nm
      dimension, and for an additive process to create aluminum oxide nanodot arrays
      without any polymeric residues or use of harsh chemicals and etchants. 

PMID- 24869479
TI  - Thermodynamics of dissolution of calcium hydroxycarboxylates in water.
AB  - Aqueous solubility of calcium l-lactate, calcium d-gluconate, and calcium d
      lactobionate increases with temperature (10-30  degrees C investigated), most
      significantly for the least soluble d-gluconate, while the calcium ion activity
      of the saturated solutions decreases with temperature, as measured
      electrochemically, most significantly for the most soluble d-lactobionate. This
      unusual behavior is discussed in relation to dairy processing and explained by
      endothermic binding of calcium to hydroxycarboxylate anions determined to have
      DeltaH degrees ass = (31 +/- 3) kJ.mol(-1) for l-lactate, (34 +/- 2) kJ.mol(-1)
      for d-gluconate, and (29 +/- 3) kJ.mol(-1) for d-lactobionate in 1:1 complexes
      with thermodynamic binding constants at 25  degrees C of Kass = 49 (l-lactate),
      88 (d-gluconate), and 140 (d-lactobionate). Quantum mechanical calculations
      within density functional theory (DFT) confirm the ordering of strength of
      binding. The complex formation is entropy driven with DeltaS degrees ass > 0,
      resulting in decreasing calcium ion activity in aqueous solutions for increasing
      temperature, even for the saturated solutions despite increasing solubility. 

PMID- 24869480
TI  - Analysis of plant Pb tolerance at realistic submicromolar concentrations
      demonstrates the role of phytochelatin synthesis for Pb detoxification.
AB  - Lead (Pb) ranks first among metals with respect to tonnage produced and released
      into the environment. It is highly toxic and therefore an important pollutant of
      worldwide concern. Plant Pb uptake, accumulation, and detoxification mobilize Pb
      into food webs. Still, knowledge about the underlying mechanisms is very limited.
      This is largely due to serious experimental challenges with respect to Pb
      availability. In most studies, Pb(II) concentrations in the millimolar range have
      been used even though the toxicity threshold is in the nanomolar range. We
      therefore developed a low-phosphate, low-pH assay system that is more realistic
      with respect to soil solution conditions. In this system the growth of
      Arabidopsis thaliana seedlings was significantly affected by the addition of only
      0.1 MUM Pb(NO3)2. Involvement of phytochelatins in the detoxification of Pb(II)
      could be demonstrated by investigating phytochelatin synthase mutants. They
      showed a stronger inhibition of root growth and a lack of Pb-activated
      phytochelatin synthesis. In contrast, other putative Pb hypersensitive mutants
      were unaffected under these conditions, further supporting the essential role of
      phytochelatins for Pb detoxification. Our findings demonstrate the need to
      monitor plant Pb responses at realistic concentrations under controlled
      conditions and provide a strategy to achieve this. 

PMID- 24869481
TI  - Electrical burns.

PMID- 24869483
TI  - Melatonin enhances the in vitro maturation and developmental potential of bovine
      oocytes denuded of the cumulus oophorus.
AB  - This study was designed to determine the effect of melatonin on the in vitro
      maturation (IVM) and developmental potential of bovine oocytes denuded of the
      cumulus oophorus (DOs). DOs were cultured alone (DOs) or with 10-9 M melatonin
      (DOs + MT), cumulus-oocyte complexes (COCs) were cultured without melatonin as
      the control. After IVM, meiosis II (MII) rates of DOs, and reactive oxygen
      species (ROS) levels, apoptotic rates and parthenogenetic blastocyst rates of MII
      oocytes were determined. The relative expression of ATP synthase F0 Subunit 6 and
      8 (ATP6 and ATP8), bone morphogenetic protein 15 (BMP-15) and growth
      differentiation factor 9 (GDF-9) mRNA in MII oocytes and IFN-tau (IFN-tau),
      Na+/K+-ATPase, catenin-beta like 1 (CTNNBL1) and AQP3 mRNA in parthenogenetic
      blastocysts were quantified using real-time polymerase chain reaction (PCR). The
      results showed that: (1) melatonin significantly increased the MII rate of DOs
      (65.67 +/- 3.59 % vs. 82.29 +/- 3.92%; P < 0.05), decreased the ROS level (4.83
      +/- 0.42 counts per second (c.p.s) vs. 3.78 +/- 0.29 c.p.s; P < 0.05) and
      apoptotic rate (36.99 +/- 3.62 % vs. 21.88 +/- 2.08 %; P < 0.05) and moderated
      the reduction of relative mRNA levels of ATP6, ATP8, BMP-15 and GDF-9 caused by
      oocyte denudation; (2) melatonin significantly increased the developmental rate
      (24.17 +/- 3.54 % vs. 35.26 +/- 4.87%; P < 0.05), and expression levels of IFN
      tau, Na+/K+-ATPase, CTNNBL1 and AQP3 mRNA of blastocyst. These results indicated
      that melatonin significantly improved the IVM quality of DOs, leading to an
      increased parthenogenetic blastocyst formation rate and quality. 

PMID- 24869485
TI  - Large-scale identification of phosphorylation sites for profiling protein kinase
      selectivity.
AB  - Protein kinase selectivity is largely governed by direct binding to the target
      site(s) on the substrate. Thus, substrate determinants identified from sequences
      around phosphorylation sites are desirable resources for matching kinases to
      their substrates. In this study, we tried to identify kinase-selective substrate
      determinants, including motif sequences, based on large-scale discovery of
      kinase/substrate pairs. For this purpose, we employed a combination strategy of
      in vitro kinase reaction followed by LC-MS/MS analysis and applied it to three
      well-studied kinases: c-AMP regulated protein kinase A (PKA), extracellular
      signal-regulated kinase 1 (ERK1), and RAC-alpha serine/threonine-protein kinase
      (AKT1). Cellular proteins were fractionated, dephosphorylated with
      thermosensitive alkaline phosphatase, phosphorylated with the target kinase, and
      digested with Lys-C/trypsin, and then phosphopeptides were enriched using TiO2
      based hydroxy acid-modified metal oxide chromatography (HAMMOC) and subjected to
      LC-MS/MS. As a result, 3585, 4347, and 1778 in vitro phosphorylation sites were
      identified for PKA, ERK1, and AKT1, respectively. As expected, these extensive
      identifications of phosphorylation sites enabled extraction of both known and
      novel motif sequences, and this in turn permitted fine discrimination of the
      specificities of PKA and AKT1, which both belong to the AGC kinase family. Other
      unique features of the kinases were also characterized, including phospho
      acceptor preference (Ser or Thr) and bias ratio of singly/multiply phosphorylated
      peptides. More motifs were found with this methodology as compared with target
      kinase phosphorylation of peptides obtained by predigestion of proteins with Lys
      C/trypsin. Thus, this approach to characterization of kinase substrate
      determinants is effective for identification of kinases associated with
      particular phosphorylation sites. 

PMID- 24869484
TI  - Accelerated postero-lateral spinal fusion by collagen scaffolds modified with
      engineered collagen-binding human bone morphogenetic protein-2 in rats.
AB  - Bone morphogenetic protein-2 (BMP-2) is a potent osteoinductive cytokine that
      plays a critical role in bone regeneration and repair. However, its distribution
      and side effects are major barriers to its success as therapeutic treatment. The
      improvement of therapy using collagen delivery matrices has been reported. To
      investigate a delivery system on postero-lateral spinal fusion, both engineered
      human BMP-2 with a collagen binding domain (CBD-BMP-2) and collagen scaffolds
      were developed and their combination was implanted into Sprague-Dawley (SD) rats
      to study Lumbar 4-5 (L4-L5) posterolateral spine fusion. We divided SD rats into
      three groups, the sham group (G1, n = 20), the collagen scaffold-treated group
      (G2, n = 20) and the BMP-2-loaded collagen scaffolds group (G3, n = 20). 16 weeks
      after surgery, the spines of the rats were evaluated by X-radiographs, high
      resolution micro-computed tomography (micro-CT), manual palpation and hematoxylin
      and eosin (H&E) staining. The results showed that spine L4-L5 fusions occurred in
      G2(40%) and G3(100%) group, while results from the sham group were inconsistent.
      Moreover, G3 had better results than G2, including higher fusion efficiency (X
      score, G2 = 2.4+/-0.163, G3 = 3.0+/-0, p<0.05), higher bone mineral density (BMD,
      G2: 0.3337+/-0.0025g/cm3, G3: 0.4353+/-0.0234g/cm3. p<0.05) and more bone
      trabecular formation. The results demonstrated that with site-specific collagen
      binding domain, a dose of BMP-2 as low as 0.02mg CBD-BMP-2/cm3 collagen scaffold
      could enhance the posterolateral intertransverse process fusion in rats. It
      suggested that combination delivery could be an alternative in spine fusion with
      dramatically decreased side effects caused by high dose of BMP-2. 

PMID- 24869486
TI  - Grids in topographic maps reduce distortions in the recall of learned object
      locations.
AB  - To date, it has been shown that cognitive map representations based on
      cartographic visualisations are systematically distorted. The grid is a
      traditional element of map graphics that has rarely been considered in research
      on perception-based spatial distortions. Grids do not only support the map reader
      in finding coordinates or locations of objects, they also provide a systematic
      structure for clustering visual map information ("spatial chunks"). The aim of
      this study was to examine whether different cartographic kinds of grids reduce
      spatial distortions and improve recall memory for object locations. Recall
      performance was measured as both the percentage of correctly recalled objects
      (hit rate) and the mean distance errors of correctly recalled objects (spatial
      accuracy). Different kinds of grids (continuous lines, dashed lines, crosses)
      were applied to topographic maps. These maps were also varied in their type of
      characteristic areas (LANDSCAPE) and different information layer compositions
      (DENSITY) to examine the effects of map complexity. The study involving 144
      participants shows that all experimental cartographic factors (GRID, LANDSCAPE,
      DENSITY) improve recall performance and spatial accuracy of learned object
      locations. Overlaying a topographic map with a grid significantly reduces the
      mean distance errors of correctly recalled map objects. The paper includes a
      discussion of a square grid's usefulness concerning object location memory,
      independent of whether the grid is clearly visible (continuous or dashed lines)
      or only indicated by crosses. 

PMID- 24869489
TI  - Total synthesis of GEX1Q1, assignment of C-5 stereoconfiguration and evaluation
      of spliceosome inhibitory activity.
AB  - An enantioselective total synthesis of GEX1Q1 has been accomplished in a
      convergent manner. The C-5 asymmetric center has now been assigned through
      synthesis. GEX1Q1 displayed slightly better spliceosome inhibitory activity over
      its C-5 epimer. The salient features of this synthesis include an asymmetric
      hetero-Diels-Alder reaction to construct the tetrahydropyran ring and a Suzuki
      cross-coupling to assemble the key segments. 

PMID- 24869490
TI  - Reactivity of C-terminal cysteines with HNO.
AB  - Nitroxyl (HNO), a potential heart failure therapeutic, is known to target
      cysteine residues to form sulfinamides and/or disulfides. Because HNO-derived
      modifications may depend on their local environment, we have investigated the
      reactivity of HNO with cysteine derivatives and C-terminal cysteine-containing
      peptides at physiological pH and temperature. Our findings indicate that the
      nature of HNO-derived modifications of C-terminal cysteines is affected by the C
      terminal carboxylate. Apart from the lack of sulfinamide formation, these studies
      have revealed the presence of new products, a sulfohydroxamic acid derivative
      (RS(O)2NHOH) and a thiosulfonate (RS(O)2SR), presumably produced under our
      experimental conditions via the intermediacy of a cyclic structure that is
      hydrolyzed to give a sulfenic acid (RSOH). Moreover, these modifications are
      formed independent of oxygen. 

PMID- 24869492
TI  - Qigong Effects on Heart Rate Variability and Peripheral Vasomotor Responses.
AB  - Population aging is occurring worldwide, and preventing cardiovascular event in
      older people is a unique challenge. The aim of this study was to examine the
      effects of a 12-week qigong (eight-form moving meditation) training program on
      the heart rate variability and peripheral vasomotor response of middle-aged and
      elderly people in the community. This was a quasi-experimental study that
      included the pre-test, post-test, and nonequivalent control group designs.
      Seventy-seven participants (experimental group = 47; control group = 30) were
      recruited. The experimental group performed 30 min of eight-form moving
      meditation 3 times per week for 12 weeks, and the control group continued their
      normal daily activities. After 12 weeks, the interaction effects indicated that
      compared with the control group, the experimental group exhibited significantly
      improved heart rate variability and peripheral vasomotor responses. 

PMID- 24869488
TI  - Investigating the relation between stochastic differentiation, homeostasis and
      clonal expansion in intestinal crypts via multiscale modeling.
AB  - Colorectal tumors originate and develop within intestinal crypts. Even though
      some of the essential phenomena that characterize crypt structure and dynamics
      have been effectively described in the past, the relation between the
      differentiation process and the overall crypt homeostasis is still only partially
      understood. We here investigate this relation and other important biological
      phenomena by introducing a novel multiscale model that combines a morphological
      description of the crypt with a gene regulation model: the emergent dynamical
      behavior of the underlying gene regulatory network drives cell growth and
      differentiation processes, linking the two distinct spatio-temporal levels. The
      model relies on a few a priori assumptions, yet accounting for several key
      processes related to crypt functioning, such as: dynamic gene activation
      patterns, stochastic differentiation, signaling pathways ruling cell adhesion
      properties, cell displacement, cell growth, mitosis, apoptosis and the presence
      of biological noise. We show that this modeling approach captures the major
      dynamical phenomena that characterize the regular physiology of crypts, such as
      cell sorting, coordinate migration, dynamic turnover, stem cell niche correct
      positioning and clonal expansion. All in all, the model suggests that the process
      of stochastic differentiation might be sufficient to drive the crypt to
      homeostasis, under certain crypt configurations. Besides, our approach allows to
      make precise quantitative inferences that, when possible, were matched to the
      current biological knowledge and it permits to investigate the role of gene-level
      perturbations, with reference to cancer development. We also remark the
      theoretical framework is general and may be applied to different tissues, organs
      or organisms. 

PMID- 24869493
TI  - Multi-level model of missed nursing care in the context of hospital merger.
AB  - The aim of this study was to delineate the multi-level relationships of
      individual registered nurse (RN) and nursing unit factors on missed nursing care.
      This was a quantitative model-building study using a descriptive, cross-sectional
      design. Surveys (N = 553) and administrative unit records from nurses in one
      hospital system undergoing merger were included. The results showed that 36% of
      the variation in missed nursing care is due to the unit context, with a
      corresponding 64% due to individual nurse differences. At the unit level,
      workload, skill mix, and critical unit type affected the amount of missed nursing
      care. At the individual nurse level, more experience, supplies problems,
      communication problems, and involvement in errors of commission all increased the
      perception of the amount of missed nursing care. Education level was not related
      to the amount of missed nursing care. The findings highlight the importance of
      unit- and individual-level interventions to redesign hospital nursing care. 

PMID- 24869498
TI  - Treat-and-repair approach to Eisenmenger syndrome.

PMID- 24869502
TI  - Energetics and solvation structure of a dihalogen dopant (I2) in (4)He clusters.
AB  - The energetics and structure of small HeNI2 clusters are analyzed as the size of
      the system changes, with N up to 38. The full interaction between the I2 molecule
      and the He atoms is based on analytical ab initio He-I2 potentials plus the He-He
      interaction, obtained from first-principle calculations. The most stable
      structures, as a function of the number of solvent He atoms, are obtained by
      employing an evolutionary algorithm and compared with CCSD(T) and MP2 ab initio
      computations. Further, the classical description is completed by explicitly
      including thermal corrections and quantum features, such as zero-point-energy
      values and spatial delocalization. From quantum PIMC calculations, the binding
      energies and radial/angular probability density distributions of the thermal
      equilibrium state for selected-size clusters are computed at a low temperature.
      The sequential formation of regular shell structures is analyzed and discussed
      for both classical and quantum treatments. 

PMID- 24869505
TI  - Taxonomic revision of the southern African genus Pachyphymus Uvarov, 1922
      (Orthoptera: Acridoidea: Euryphyminae).
AB  - The southern African endemic genus, Pachyphymus Uvarov, 1922 (Orthoptera:
      Acrididae: Euryphyminae), is the only genus in the Euryphyminae subfamily with
      enlarged and hump-shaped pronotal crests. Here, we redescribe two species using
      newly evaluated diagnostic characters: P. carinatus Dirsh, 1956 and P.
      cristulifer (Serville, 1838); and describe two new species: P. samwaysi n. sp.
      and P. namaquensis n. sp. Of the 23 genera of Euryphyminae, Pachyphymus is
      arguably the most morphologically distinct. However, the species of Pachyphymus,
      like those of the other Euryphyminae, are difficult to distinguish
      morphologically because of a high degree of intraspecific variation. Height and
      shape of the pronotal crests and rugosity of the pronotum were previously
      considered diagnostic but are strongly variable within species. Degree of
      infumation of the hind wing is strongly conserved and is the single best
      diagnostic character in most cases. However, one population of P. cristulifer,
      which is isolated from the mainland population by a mountain range, shows very
      little conservation in this character. Additionally, one population of P.
      namaquensis and one population of P. cristulifer, both from outlying regions of
      their geographic range have intermediate wing infumation as well as other
      morphological characters. This may indicate recent or ongoing hybridization or
      divergence of the geographically overlapping species. This study emphasizes the
      need for molecular analysis to complement detailed morphological diagnosis of the
      species of Euryphyminae, a notoriously under-studied and taxonomically
      problematic group.  

PMID- 24869503
TI  - Resting-state slow wave power, healthy aging and cognitive performance.
AB  - Cognitive functions and spontaneous neural activity show significant changes over
      the life-span, but the interrelations between age, cognition and resting-state
      brain oscillations are not well understood. Here, we assessed performance on the
      Trail Making Test and resting-state magnetoencephalographic (MEG) recordings from
      53 healthy adults (18-89 years old) to investigate associations between age
      dependent changes in spontaneous oscillatory activity and cognitive performance.
      Results show that healthy aging is accompanied by a marked and linear decrease of
      resting-state activity in the slow frequency range (0.5-6.5 Hz). The effects of
      slow wave power on cognitive performance were expressed as interactions with age:
      For older (>54 years), but not younger participants, enhanced delta and theta
      power in temporal and central regions was positively associated with perceptual
      speed and executive functioning. Consistent with previous work, these findings
      substantiate further the important role of slow wave oscillations in
      neurocognitive function during healthy aging. 

PMID- 24869506
TI  - A comparative study of populations of Ectopleura crocea and Ectopleura ralphi
      (Hydrozoa, Tubulariidae) from the Southwestern Atlantic Ocean.
AB  - Ectopleura crocea (L. Agassiz, 1862) and Ectopleura ralphi (Bale, 1884) are two
      of the nominal tubulariid species recorded for the Southwestern Atlantic Ocean
      (SWAO), presumably with wide but disjunct geographical ranges and similar
      morphologies. Our goal is to bring together data from morphology, histology,
      morphometry, cnidome, and molecules (COI and ITS1+5.8S) to assess the taxonomic
      identity of two populations of these nominal species in the SWAO. We have
      observed no significant difference or distributional patterns between the so
      called Brazilian E. ralphi and Argentine E. crocea for both morphological and
      molecular data. Therefore, SWAO populations of Ectopleura belong to the same
      species. In a broader view, it is difficult to find decisive character
      distinguishing E. crocea from E. ralphi, and both species have indeed recently
      been synonymized, with the binomen E. crocea having nomenclatural priority.
      Geographically broader genetic analysis should be carried out in order to test
      the validity of this synonymy because taxonomical procedures such as studying
      type specimens and documenting broad phenotypic variability have not yet been
      conducted. 

PMID- 24869507
TI  - A new Leptolalax from the mountains of Sabah, Borneo (Amphibia, Anura,
      Megophryidae).
AB  - A new species of Leptolalax is described from Kinabalu National Park in western
      Sabah, Malaysian Borneo. The new species had been assigned to L. dringi, L.
      gracilis, or L. fritinniens in the past. It differs from all congeners, including
      these species, by a unique combination of morphological characters, including
      small body size, rounded snout, narrower interorbital than upper eyelid, basal
      toe webbing, smooth skin with tiny tubercles on dorsum and dorsal side of head,
      small pectoral glands, absence of supraaxillary glands and ventrolateral
      glandular ridges, spotted venter, advertisement call consisting of long series of
      1-149 notes, each composed of three or four pulses, and dominant frequency at
      6.90-7.35 kHz, without prominent frequency modulation. 

PMID- 24869508
TI  - A new species of pine anole from the Sierra Madre del Sur in Oaxaca, Mexico
      (Reptilia, Squamata, Dactyloidae: Anolis).
AB  - We describe the new species Anolis peucephilus sp. nov. from the Pacific versant
      of southern Mexico. Anolis peucephilus differs from all congeners by having a
      combination of (1) smooth ventral scales; (2) usually a patch of three greatly
      enlarged supraocular scales; (3) extremely short hind legs, longest toe of
      adpressed hind leg reaching to a point between levels of axilla and ear opening,
      ratio shank length/snout-vent length 0.18-0.21; (4) circumnasal usually in
      contact with first supralabial; and (5) a large yellowish orange dewlap in males
      and a very small to small white dewlap in females. In external morphology, A.
      peucephilus is most similar to A. omiltemanus from which it differs by having
      even shorter hind legs with the longest toe of adpressed hind leg reaching to a
      point between levels of axilla and ear opening (versus usually to ear opening,
      occasionally to slightly beyond ear opening or to a point between shoulder and
      ear opening in A. omiltemanus), a slightly larger dewlap in females, to 64 mm2
      (versus to 41 mm2 in A. omiltemanus), the circumnasal usually in contact with the
      first supralabial (versus those scales separated by the presence of a subnasal in
      A. omiltemanus), and 4-6 internasal scales in the new species (versus usually 6-7
      in A. omiltemanus). Furthermore, A. peucephilus differs from A. omiltemanus in
      hemipenial morphology (no finger-like processus on asulcate side in A.
      peucephilus versus such a processus present in A. omiltemanus). Also, in a
      preliminary molecular genetic analysis of the mitochondrial CO1 gene fragment, A.
      peucephilus has a genetic distance of 11.5% from A. omiltemanus. Anolis
      peucephilus was collected at night while the lizards were sleeping in pine trees,
      2-10 m above the ground.

PMID- 24869509
TI  - Neotropical genera of Naucoridae (Hemiptera: Heteroptera: Nepomorpha): new
      species of Placomerus and Procryphocricos from Guyana and Venezuela.
AB  - The Neotropical fauna of saucer bugs (Naucoridae) currently includes four
      monotypic genera. Recent extensive collecting in Venezuela has produced three new
      species in two of these genera. In addition, undetermined Guyanan specimens of
      one of the new species were found in the United States National Museum of Natural
      History. Thus, described here are Placomerus obscuratus n. sp. from Guyana and
      Venezuela with brachypterous and macropterous hindwing forms, and two species of
      Procryphocricos from Venezuela. Procryphocricos quiu n. sp. is described from the
      brachypterous forewing form and Procryphocricos macoita n. sp. from both
      brachypterous and macropterous forms. Previously described species also are
      discussed. 

PMID- 24869510
TI  - A new species of Choerophryne (Anura, Microhylidae) from the central cordillera
      of Papua New Guinea.
AB  - We describe a new species of very small microhylid frog in the genus Choerophryne
      from the upper Strickland River area, Western and Southern Highlands Provinces,
      Papua New Guinea. Choerophryne gracilirostris sp. nov. can be distinguished from
      congeners by the following combination of characters: small size (SUL 13.5-14.7
      mm), moderately long and narrow snout, first finger without expanded disk and
      advertisement call consisting of 3-5 distinctly pulsed notes repeated in long
      sequences. Males in the type series were calling from within leaf litter in
      primary hill rainforest (213-1368 m a.s.l.). The new species is the third
      Choerophryne known from the southern side of New Guinea's central cordillera.
      Measurements of a juvenile specimen (rare because most Choerophryne collected are
      calling males) demonstrate that the distinctive rostral projection of this genus
      exhibits pronounced positive allometry. 

PMID- 24869511
TI  - A new species of Orthosia Ochsenheimer, 1816 from North-East Kazakhstan
      (Lepidoptera, Noctuidae).
AB  - Orthosia Ochsenheimer, 1816 is a Holarctic-Oriental noctuid genus comprising more
      than 60 described species, with most distributed in the eastern and southeastern
      Palaearctic and Oriental regions. Many species have recently been described from
      Asia (Hreblay 1991, 1993, 1994; Yoshimoto 1993; Hreblay & Plante 1994; Hreblay &
      Ronkay 1998, 1999; Ronkay et al. 2010, Saldaitis et al. 2011, etc.). The O.
      incerta species-group includes 10 described species (see Ronkay et al. 2001), and
      during the course of faunistic studies on the Noctuidae of North-East Kazakhstan,
      a new member of this species-group was found; it is described herein as new.  

PMID- 24869512
TI  - Hydrellia Robineau-Desvoidy (Diptera: Ephydridae) from Brazil with an emphasis on
      the faunas from the states of Parana and Rio de Janeiro.
AB  - With more than 200 species worldwide, Hydrellia Robineau-Desvoidy is the largest
      genus of the family Ephydridae (Diptera). However, knowledge of this genus is
      much reduced in Brazil and throughout the Neotropical Region, where only 8
      species are known, including one from Brazil (H. xanthocera Cresson). The
      objective of this study is to review the species of Hydrellia from Brazil, with
      an emphasis on the faunas of Parana and Rio de Janeiro states. Six new species
      are described: H. bocaiuvensis sp. nov. (Brazil, Parana, Bocaiuva do Sul, 25
      degrees 14.9'S, 49 degrees 8.9'W, 890 m), H. longiseta sp. nov. (Brazil, Parana,
      Parque Iguacu, 25 degrees 33.4'S, 49 degrees 13.6'W, 880 m),H. vilelai sp. nov.
      (Brazil, Parana, Bocaiuva do Sul, 25 degrees 16.6'S, 48 degrees 58.5'W, 770 m),
      H. simplex sp. nov. (Brazil, Parana, Parque Iguacu, 25 degrees 33.4'S, 49 degrees
      13.6'W, 880 m) e H. schneiderae sp. nov. (Brazil, Parana, Parque Iguacu (25
      degrees 33.4'S, 49 degrees 13.6'W, 880 m), H. similis sp. nov. (Brazil, Parana,
      Bocaiuva do Sul, 25 degrees 14.9'S, 49 degrees 8.9'W, 890 m). Seven new registers
      are recorded: H. agitator (Para), H. apalachee (Parana and Rio de Janeiro), H.
      calverti (Amazonas and Parana), H. cavator (Rio de Janeiro), H. tibialis
      (Amazonas, Parana and Rio de Janeiro), H. vulgaris (Parana, Sao Paulo, Santa
      Catarina and Rio de Janeiro), H. wirthi (Para, Parana and Santa Catarina).
      Together with H. xanthocera, Hydrellia now includes 14 species from Brazil.

PMID- 24869514
TI  - New species and records of the earthworm genus Ramiellona (Annelida, Oligochaeta,
      Acanthodrilidae) from southern Mexico and Guatemala.
AB  - Three new species from the Mexican states of Tabasco and Chiapas are added to the
      acanthodrilid earthworm genus Ramiellona, R. microscolecina sp. nov., R.
      tojolabala sp. nov. and R. teapaensis sp. nov. They belong to a group of species
      with penial setae and last pair of hearts in segment 12. All are holandric and
      the spermathecae have either a flat circular diverticle in a segment anterior to
      that of the ampulla (R. microscolecina sp. nov. and R. tojolabala sp. nov.) or
      two ovoidal and sessile diverticles on opposite sides in the same segment of the
      ampulla (R. teapaensis sp. nov.). Ramiellona americana (Gates) is re-described
      from a single specimen from central Guatemala, and the diagnosis of Ramiellona
      lasiura (Graff) from El Salvador is emended after reinvestigating a paratype
      specimen from the Senckenberg Naturmuseum Frankfurt. On the basis of several
      individuals from different populations of the Mexican states of Chiapas and
      Tabasco, the morphological variation of Ramiellona strigosa setosa Righi is
      described and its relationship with the Guatemalan Ramiellona strigosa strigosa
      Gates and Ramiellona eiseni (Michaelsen) is discussed. Finally, the position of
      Ramiellona within Acanthodrilidae and its relation to genera of the doubtful
      Octochaetidae is discussed. 

PMID- 24869515
TI  - Two new species of the genus Timia (Diptera: Ulidiidae) with a key to species
      with microtrichose black scutellum.
AB  - Two new species of Timia are described and figured. Timia (Empyelocera) altaica
      Galinskaya sp. nov. from Altai (Russia), Timia (Empyelocera) mokhnata Galinskaya
      sp. nov. from Eastern Pamir (Tajikistan) and T. (E.) nigrimana (Loew, 1866)
      differ from all other species of Timia in having scutellum flattened superiorly,
      microtrichose only superiorly; anepisternum shining along the whole surface,
      without microtrichosity; wing entirely transparent, without spots. Timia
      (Empyelocera) altaica Galinskaya sp. nov. differs from both of them by the
      posteroapical extension of cell bcu short, 0.8 times as long as transverse
      section of vein Cu. Timia (Empyelocera) mokhnata Galinskaya sp. nov. is similar
      to T. (E.) nigrimana (Loew, 1866) in having posteroapical extension of cell bcu
      long, more than 2 times as long as transverse section of vein Cu; the new species
      differs by the frons, scutum and pleura with long (about 0.6-0.8 times as long as
      setae) hairs; the orbit of frons with whitish microtrichose triangular spot at
      its anterior margin. A key to the five species with black microtrichose
      scutellum, descriptions and illustrations are provided. 

PMID- 24869513
TI  - A new paper wasp from Late Eocene of France (Hymenoptera: Vespidae: Polistinae).
AB  - The new vespid genus and species Palaeopolistes jattioti gen. et. sp. nov. is
      described from the Late Eocene of Monteils (Gard, France). The new taxon has
      clear features of the Polistinae but its tribal assignment is uncertain. 

PMID- 24869516
TI  - A new species of Desmopachria Babington (Coleoptera: Dytiscidae) from Cuba with a
      prediction of its geographic distribution and notes on other Cuban species of the
      genus.
AB  - A new species, Desmopachria andreae sp. n. is described from Cuba. Diagnostic
      characters including illustrations of male genitalia are provided and illustrated
      for the five species of the genus occurring on the island. For these five species
      both a simple key to adults and maps of their known distribution in Cuba are also
      provided. Using a Maximun Entropy method (MaxEnt), a distribution model was
      developed for D. andreae sp.n. Based on the model's predictions, this species has
      a higher probability of occurring in high altitude forests (above 1000 m a.s.l.),
      characterised by relatively low temperatures especially during the hottest and
      wettest seasons, specifically, the mountainous areas of the Macizo de Guamuhaya
      (Central Cuba), Sierra Maestra (S Cuba) and Nipe-Sagua-Baracoa (NE Cuba). In some
      of these areas the species has not yet been recorded, and should be searched for
      in future field surveys. 

PMID- 24869517
TI  - Sustaining the development of world's foremost journal in biodiversity discovery
      and inventory: Zootaxa editors and their contributions.

PMID- 24869518
TI  - Evaluation of patients' questions to identify gaps in information provision to
      infertile patients.
AB  - The objective of this observational study was to identify gaps in written patient
      information at an infertility clinic, by systematically analysing the questions
      raised by infertile patients in a forum or during 'phone and group consultations.
      This was done (1) by identifying themes raised by patients undergoing Medically
      Assisted Reproduction and (2) by determining to what extent the questions asked
      by patients were absent from information leaflets provided by the clinic. A total
      of 193 questions were included and 24 different themes identified (e.g. blood
      loss during treatment, use of and side-effects of medication). Half of the
      patients' questions could not or could only partially be answered using the
      conventional patient information leaflets (51%). Healthcare providers should be
      aware that the information they provide does not necessarily cover all
      information needs. The involvement of patients in the creation of information,
      for instance through an approach such as that described in the paper, can provide
      insight into the informational needs of patients, and help healthcare providers
      keep their information up-to-date and patient-centred.

PMID- 24869519
TI  - Adult immunization.

PMID- 24869520
TI  - New species of the deep-sea munnopsid genus Tytthocope (Crustacea, Isopoda,
      Asellota) from the South Atlantic and the Southern Ocean.
AB  - In the benthic samples collected during the deep-sea expeditions ANDEEP from the
      Weddell Sea and DIVA from the Argentine Basin the isopod family Munnopsidae was
      the most specious and numerous. Among the collected munnopsids three new species
      of Tytthocope Wilson & Hessler, 1981 have been discovered. Tytthocope is one of
      six genera of the subfamily Eurycopinae. It differs from other genera of the
      Eurycopinae by having a strongly reduced pereonite 7 and inflated pleotelson.
      Until now the genus consisted of five described species: four of them are known
      from the northern Atlantic and only one species, T. sulcifrons (Barnard, 1920)
      was described from the southern Atlantic off the South Africa coast. The five
      known species of Tytthocope have been recorded from depths less than 1461 m.
      Descriptions of three new species of Tytthocope collected in the South Atlantic
      and Southern Ocean at depths between 1530-4608 m, T. divae sp. nov., T. fahrbachi
      sp. nov. and T. longitelson sp. nov. are presented in the paper. T. sulcifrons is
      redescribed herein based on the type material. 

PMID- 24869521
TI  - Indonesian species of Dilatognathus Kluge 2012 (Ephemeroptera, Leptophlebiidae,
      Choroterpes s.l.) and species-specific sexual dimorphism in development of
      maxilla.
AB  - Larvae, subimagoes and imagoes of both sexes reared from larvae of a new species
      Choroterpes (Dilatognathus) bogori sp.n. from Java are described. Formerly this
      species was described by Ulmer (1939) under the wrong name "Choroterpides exiguus
      (Eaton 1884)". In all species of Dilatognathus, maxilla of last instar larva has
      the same structure, but in Ch. (D.) cataractae its structure is different in
      previous instars, being different in males and females.  

PMID- 24869522
TI  - New quill mites (Cheyletoidea: Syringophilidae) parasitizing the black-headed
      paradise-flycatcher Terpsiphone rufiventer (Passeriformes: Monarchidae) in Gabon.
AB  - A new genus of quill mites (Cheyletoidea: Syringophilidae) and two new species
      Pipicobia terpsiphoni gen. nov. and sp. nov. and Syringophiloidus furthi sp. nov.
      parasitizing the black-headed paradise-flycatcher Terpsiphone rufiventer
      (Swainson) (Passeriformes: Monarchidae) in Gabon are described. Three species of
      the Neopicobia Skoracki, 2011 are moved to the newly established genus: Pipicobia
      locustella (Skoracki, Bochkov and Wauthy, 2004) comb. nov., Pipicobia
      pyrrholaemus (Skoracki and Glowska, 2008) comb.nov., and Pipicobia glossopsitta
      (Skoracki, Glowska and Sikora, 2008) comb.nov. Syringophilids are recorded on
      hosts of the family Monarchidae and in Gabon for the first time. A key to the
      genera of the subfamily Picobiinae is proposed. 

PMID- 24869523
TI  - A new Cleotomiris species (Hemiptera: Heteroptera: Miridae: Phylinae) from North
      Korea.
AB  - Cleotomiris josifovi is described from the vicinity of Pyong Kang, North Korea.
      The description of this new species is provided with scanning micrographs of
      selected structures, and digital microscopic images of habitus and genitalia. 

PMID- 24869524
TI  - A new genus and species of myrmecophilous brentid beetle (Coleoptera: Brentidae)
      inhabiting the myrmecophytic epiphytes in the Bornean rainforest canopy.
AB  - Pycnotarsobrentus inuiae Maruyama & Bartolozzi, gen. nov. and sp. nov.
      (Brentinae: Eremoxenini) is described from the Lambir Hills National Park, Borneo
      (Sarawak, Malaysia) based on specimens collected from Crematogaster difformis F.
      Smith, 1857 ant nests in the myrmecophytic epiphytic ferns Platycerium crustacea
      Copel. and Lecanopteris ridleyi H. Christ. A second species of Pycnotarsobrentus
      is known from Malaysia but is represented by only one female and consequently not
      yet described pending discovery of a male. Pycnotarsobrentus belongs to the tribe
      Eremoxenini and shares some character states with the African genus Pericordus
      Kolbe, 1883. No species of Eremoxenini with similar morphological modifications
      are known from the Oriental region. 

PMID- 24869525
TI  - Revision of the Oriental leafhopper genus Destinoides Cai & He (Hemiptera:
      Cicadellidae: Ledrinae), with a new synonym and two new combinations.
AB  - The leafhopper genus Destinoides Cai & He is revised to include two species D.
      latifrons (Walker 1851, Ledra) n. comb. and D. conspicuus (Distant 1907,
      Petalocephala) n. comb. Destinoides fasciata Cai & He, 2000 is placed as a junior
      synonym of D. latifrons, syn. nov. These two species are redescribed and
      illustrated in detail and a key is given based on the males. 

PMID- 24869526
TI  - Foveocrotaphus gen. n. and F. burmanicus sp. n.: a new genus and species of
      Physocrotaphini from Myanmar (Coleoptera: Carabidae: Anthiinae).
AB  - Foveocrotaphus gen. nov. and new species F. burmanicus from Myanmar is described.
      The new genus is similar to Physocrotaphus Parry, with respect to shape and
      structure of ligula and paraglossae. The two genera can be diagnosed easily by
      median tooth of mentum, bifid in Physocrotaphus, i.e. Foveocrotaphus gen. n. has
      simple, narrow and pointed. Is distinguishable from all other known
      Physocrotaphini genera by narrower pronotum, very stout ligula combined with long
      and simple median tooth of mentum and by male sternites 2 and 3 with one big
      shared median depression. 

PMID- 24869527
TI  - The genus Emitrombidium Lombardini, 1949 (Actinotrichida: Trombidiidae)
      resurrected.
AB  - Emitrombidium giocondi sp. nov., a second species of Emitrombidium is described
      based on postlarval forms originating from Turkey. The history of the genus is
      retraced. The previous conjectures about the uncertain family affiliation of
      Emitrombidium are clarified and the genus is reinstated as a member of
      Trombidiidae. Hitherto records suggest the Mediterranean and Pontic distribution
      of the genus. 

PMID- 24869528
TI  - A taxonomic note on Homorosoma horridulum Voss, 1958 (Coleoptera: Curculionidae),
      with new records from Taiwan.
AB  - Homorosoma horridulum Voss 1958 (Curculionidae: Ceutorhynchinae) was described
      from Kuatun, China, based on two specimens in the J. Klapperich collection. Since
      that time it has been uninvestigated for more than half a century, except by
      Colonnelli (2004), who listed it in his world catalogue of the subfamily. The
      recent examination of the holotype of H. horridulum revealed that it should be
      placed in the genus Scleropteroides Colonnelli 1979. In addition, Scleropteroides
      specimens from Taiwan agree well with the holotype of H. horridulum not only in
      general appearance but also in male genital structures. Here we transfer
      Homorosoma horridulum Voss 1958 to the genus Scleropteroides Colonnelli 1979 as
      Scleropteroides horridulus (Voss 1958) and record the species from Taiwan for the
      first time. Depositories of specimens examined are abbreviated as follows: CMNC:
      Canadian Museum of Nature, Ottawa; CWOB: C.W. O'Brien collection, Green Valley,
      Arizona, USA; EUMJ: Laboratory of Environmental Entomology, Faculty of
      Agriculture, Ehime University, Matsuyama, Japan; NIAES: National Institute for
      Agro-Environmental Sciences, Tsukuba, Japan; SMNH: Swedish Museum of Natural
      History, Stockholm, Sweden; and ZIN: Zoological Institute, Russian Academy of
      Sciences, St. Petersburg, Russia. Before going further, we wish to express our
      cordial thanks to R. S. Anderson, Francois Genier (CMNC), H. Kojima (Tokyo
      University of Agriculture), M. Sakai (Ehime University), C.W. O'Brien, and B.
      Viklund (SMNH) for the loan or donation of specimens examined. The first author
      thanks the late P. Lindskog (SMNH) for the help during his first visit to
      Stockholm. The study by the first author was supported by Grant No 13-04-01002
      from the Russian Foundation for Basic Research. 

PMID- 24869529
TI  - Four new species of Cladorhizidae (Porifera, Demospongiae, Poecilosclerida) from
      the Northeast Pacific.
AB  - Interest in cladorhizid sponges has grown rapidly in the past 19 years since a
      unique feeding strategy, carnivory, was described by Vacelet and Boury-Esnault in
      1995. Since that time, 31% of the 133 extant cladorhizids have been described.
      Previously, seven species of cladorhizid sponges were known from the Northeast
      Pacific. Here we describe four additional species, including two species of
      Asbestopluma and two species of Cladorhiza. We report on species ranges, habitat,
      and ecology, including one from a chemosynthetic environment that appears to be
      using methane-oxidizing bacteria as a nutrient source. In fact, three of the four
      species described here were found in chemosynthetic habitats. The presence of
      small crustacean prey was also documented for three of these species.  

PMID- 24869530
TI  - On the identity of Cancer urania Herbst, 1801 (Crustacea: Decapoda: Brachyura:
      Leucosiidae).
AB  - Cancer urania Herbst, 1801, is the type species of the leucosiid genus Coleusia
      Galil, 2006. Its identity has been a subject of confusion due to various
      taxonomical and nomenclatural issues. We redescribe the species, discuss its
      complex history and taxonomy, and a female syntype is designated as the lectotype
      of the species to clarify any lingering ambiguities concerning the type material
      of Cancer urania Herbst, 1801. 

PMID- 24869531
TI  - A new species of Coleusia Galil, 2006 (Decapoda: Brachyura: Leucosiidae) from
      southern Asia.
AB  - A new species of leucosiid crab of the genus Coleusia Galil, 2006, is described
      from South and Southeast Asia. Coleusia huilianae n. sp. is distinguished from
      the superficially similar C. urania (Herbst, 1801) in the shape of the apical
      process of the first male gonopod which is digitate and curved laterally in the
      former (beak-like and curved interiorly in the latter); possessing smaller and
      sparser granulation on the posterior and lower margin of the cheliped and
      ambulatory meri; and the granulation is entirely missing from the lower external
      surface of the palm. 

PMID- 24869532
TI  - Taxonomic assessment of Alligator Snapping Turtles (Chelydridae: Macrochelys),
      with the description of two new species from the southeastern United States.
AB  - The Alligator Snapping Turtle, Macrochelys temminckii, is a large, aquatic turtle
      limited to river systems that drain into the Gulf of Mexico. Previous molecular
      analyses using both mitochondrial and nuclear DNA suggested that Macrochelys
      exhibits significant genetic variation across its range that includes three
      distinct genetic assemblages (western, central, and eastern = Suwannee). However,
      no taxonomic revision or morphological analyses have been conducted previously.
      In this study, we test previous hypotheses of distinct geographic assemblages by
      examining morphology, reanalyzing phylogeographic genetic structure, and
      estimating divergence dating among lineages in a coalescent framework using
      Bayesian inference. We reviewed the fossil record and discuss phylogeographic and
      taxonomic implications of the existence of three distinct evolutionary lineages.
      We measured cranial (n=145) and post-cranial (n=104) material on field-captured
      individuals and museum specimens. We analyzed 420 base pairs (bp) of
      mitochondrial DNA sequence data for 158 Macrochelys. We examined fossil
      Macrochelys from ca. 15-16 million years ago (Ma) to the present to better assess
      historical distributions and evaluate named fossil taxa. The morphological and
      molecular data both indicate significant geographical variation and suggest three
      species-level breaks among genetic lineages that correspond to previously
      hypothesized genetic assemblages. The holotype of Macrochelys temminckii is from
      the western lineage. Therefore, we describe two new species as Macrochelys
      apalachicolae sp. nov. from the central lineage and Macrochelys suwanniensis sp.
      nov. from the eastern lineage (Suwannee River drainage). Our estimates of
      divergence times suggest that the most recent common ancestor (MRCA) of M.
      temminckii (western) and M. apalachicolae (central) existed 3.2-8.9 Ma during the
      late Miocene to late Pliocene, whereas M. temminckii-M. apalachicolae and M.
      suwanniensis last shared a MRCA 5.5-13.4 Ma during the mid-Miocene to early
      Pliocene. Examination of fossil material revealed that the fossil taxon M.
      floridana is actually a large Chelydra. Our taxonomic revision of Macrochelys has
      conservation and management implications in Florida, Georgia, and Alabama. 

PMID- 24869533
TI  - New species of Hybos Meigen from Northwest China (Diptera: Empidoidea,
      Hybotinae).
AB  - The species of the genus Hybos Meigen from Northwest China are reviewed. The
      following five species are described as new to science: Hybos elongatus sp. nov.,
      H. flavitibialis sp. nov., H. projectus sp. nov., H. qinlingensis sp. nov., and
      H. xii sp. nov. A key to the 17 species of the genus Hybos from Northwest China
      is provided.  

PMID- 24869534
TI  - Schistura phamhringi, a new stone loach from Chindwin Basin in Manipur, India
      (Cypriniformes: Nemacheilidae).
AB  - Schistura phamhringi, new stone loach, is described from Dutah Stream, tributary
      of the Yu River (Chindwin basin), near Larong Village, Chandel District, Manipur,
      India. It is distinguished from all its congeners by a unique combination of
      characters: 6-7 black saddles, each continued on both flanks forming broad
      diamond-shaped black bars with narrow ventral margin; bars superimposed on a grey
      stripe along lateral line; upper lip with numerous melanophores; black basicaudal
      bar arc-shaped; complete lateral line; and prominent oar-like suborbital flap on
      male. 

PMID- 24869535
TI  - A new species of arboreal forest-dwelling gecko (Hemidactylus: Squamata:
      Gekkonidae) from coastal Kenya, East Africa.
AB  - A new species of Hemidactylus, H. mrimaensis sp. nov., is described from coastal
      kaya forests of Kenya. This small-sized, arboreal gecko may be distinguished from
      its probable close relative, the sympatric H. mabouia, by its more slender
      habitus, golden color, small adult body length (maximum SVL 50 mm in females) and
      features of scalation including keeled dorsal tubercles in 11-14 longitudinal
      rows, pointed tubercles on tail larger than those on the dorsum, and 32-34
      precloacal pores in males. This gecko may be endemic to the coastal forests and
      given the ongoing threats to this habitat, the species is of high conservation
      concern. 

PMID- 24869537
TI  - Two new species of the tooth-carp Aphanius (Teleostei: Cyprinodontidae) and the
      evolutionary history of the Iranian inland and inland-related Aphanius species .
AB  - Two new species of Aphanius are described from the Kol drainage in southern Iran
      (Aphanius darabensis n. sp.) and the endorheic Kavir Basin in northern Iran (A.
      kavirensis n. sp.), and compared with eight closely related species. Aphanius
      darabensis n. sp. is sister to A. shirini, from which it is distinguished by
      molecular characters (cytochrome b) and the combination of three morphological
      characters: 9-18 flank bars in males (vs. 7-10), females with irregular vertical
      patches of brown color on the flank (vs. prominent dark brown blotches of round
      or irregular shape), and symmetrically-shaped triangular to trapezoid otoliths
      with a rostrum distinctly longer than the antirostrum (vs. quadrangular to
      trapezoid otoliths with short and equally sized rostrum and antirostrum).
      Aphanius kavirensis n. sp. is closely related to a group containing A. sophiae,
      A. mesopotamicus and A. pluristriatus, from which it is distinguished by
      cytochrome b characters and the combination of three morphological characters:
      females with irregularly arranged large blotches of dark brown color on the
      flank, short pectoral fin in both sexes (13.4-18.1% SL in males, 11.2-18.3% SL in
      females), and asymmetrically shaped triangular to trapezoid otoliths with a
      pronounced predorsal region. Our tree based on the cytochrome b data demonstrates
      that the Iranian inland and inland-related Aphanius species (IIRAS) form a
      monophyletic clade with three subclades (A. vladykovi -, A. shirini -, A. sophiae
      subclades). The A. sophiae subclade, which is the most diverse of the three
      subclades, can be further divided into three lineages (A. isfahanensis -, A.
      farsicus -, A. sophiae lineages). The temporal diversification of the IIRAS clade
      is discussed and two evolutionary groups of Aphanius are depicted. Aphanius
      vladykovi, together with A. shirini, A. darabensis n. sp. and A. isfahanensis
      characterize the "old" evolutionary group. Their divergences may have happened 10
      5 m.y. ago (Late Miocene-Early Pliocene). Aphanius farsicus, A. arakensis, A.
      sophiae, A. mesopotamicus, and A. pluristriatus, together with Aphanius
      kavirensis n. sp., represent the "young" evolutionary group, which developed in
      the Late Pleistocene (100,000-11,700 y. ago) and Early to Middle Holocene (c.
      11,700-4,000 y. ago). 

PMID- 24869536
TI  - Spionidae (Polychaeta: Canalipalpata: Spionida) from seamounts in the NE
      Atlantic.
AB  - Spionidae (Polychaeta) collected from seamounts in the Atlantic Ocean were
      studied. Altogether six species were found of which two are new to science and
      one belongs to a new genus. Aonidella cf. dayi Maciolek in Lopez-Jamar, 1989 and
      Glandulospio orestes gen. et sp. nov. were the most common species and occurred
      on both the Great and Little Meteor Seamount, the Irving Seamount and the Hyeres
      Seamount. Laonice norgensis Sikorski, 2003 and Malacoceros jirkovi Sikorski, 1992
      have a wider distribution in the North Atlantic, including the Mediterranean Sea
      in case of L. norgensis. Aonides selvagensis Brito, Nunez and Riera, 2006 is only
      known from the Macaronesian Region. Dipolydora paracaulleryi sp. nov. has been
      collected from both the Great and Little Meteor Seamounts. All species are
      compared with morphological similar species and their taxonomy is discussed.
      Detailed descriptions are provided for the species new to science and
      descriptions of the previously known species are amended. Accompanying
      histological studies revealed the presence of very strong dorsoventral
      musculature in A. cf. dayi and for G. orestes gen. et sp. nov. the presence of
      glandular organs in the middle body region. Laonice maciolekae Aguirrezabalaga &
      Ceberio, 2005 was found to be a junior synonym of L. appellofi Soderstrom, 1920
      and is formally synonymised. Molecular data suggest gene flow between seamounts
      and autochthonous as well as allochthonous larval recruitment for different
      species. The results of previous studies by other authors, that polychaete
      communities of the North Atlantic Seamounts are characterized by low diversity,
      low rates of endemism, and the predominance of widely distributed (and
      cosmopolitan) species is not corroborated by our results.  

PMID- 24869538
TI  - More than 35 years of studies on marine nematodes from Tunisia: a checklist of
      species and their distribution.
AB  - This work provides an inventory of species of free-living nematodes from Tunisian
      waters, based on samples collected from September 1977 until March 2013. Sediment
      samples were taken from 8 ecosystems: the Lagoons of Bizerte, Ghar El Melh and
      Bou Ghrara, Northern and Southern Lakes of Tunis, Old Harbor of Bizerte, Bizerte
      Bay and Ichkeul Lake. A total of 31 families, 133 genera, and 249 species of
      marine nematodes are currently known from Tunisia. The Xyalidae (with 30
      species), Cyatholaimidae (25), Chromadoridae and Linhomoeidae (each 21) and
      Comesomatidae (20) are the richest families. Among them, Daptonema (with 9
      species), Pomponema and Sabatieria (with 7 each) are the most species-rich
      genera. Some species were recovered only from a specific type of ecosystem. In
      detail, 109 species were recovered from lagoons, 56 species from sandy beaches
      and 6 species from mudflats. The 78 remaining species were widely distributed in
      Tunisian waters and four of these (Terschellingia longicaudata, Oncholaimus
      campylocercoides, Sabatieria pulchra and Theristus flevensis) were present in
      most of the 8 ecosystems studied.

PMID- 24869539
TI  - Testing the validity of Northern European species in the Chrysis ignita species
      group (Hymenoptera: Chrysididae) with DNA barcoding.
AB  - Containing more than a hundred species, the Chrysis ignita species group is the
      largest and one of the most taxonomically challenging groups in its genus. It has
      not been possible to resolve the taxonomy of the group using traditional methods
      due to the lack of robust diagnostic morphological characters. Here we present
      the results of a molecular analysis designed to delimit species in the Chrysis
      ignita group for the first time; using mitochondrial sequence data for 364 in
      group specimens consisting of all 18 species known to occur in Northern Europe.
      Two mitochondrial loci were analysed: a COI gene fragment, and a continuous DNA
      sequence consisting of 16S rRNA, tRNA<sup>Val</sup>, 12S rRNA and ND4. Two
      approaches were employed for delimiting species: (1) genetic distance analysis
      based on the standard COI barcode sequences and; (2) phylogenetic analysis of the
      COI fragment together with rRNA genes. Both analyses yielded trees with similar
      topology, but support values for nodes were higher using the second approach.
      Fifteen species were distinguished in all analyses: Chrysis angustula Schenck,
      1856, C. brevitarsis Thomson, 1870, C. clarinicollis Linsenmaier, 1951, C.
      corusca Valkeila, 1971, C. fulgida Linnaeus, 1761, C. ignita (Linnaeus, 1758), C.
      impressa Schenck, 1856, C. iris Christ, 1791, C. leptomandibularis Niehuis, 2000,
      C. longula Abeille de Perrin, 1879, C. ruddii Shuckard, 1837, C. schencki
      Linsenmaier, 1968, C. subcoriacea Linsenmaier, 1959, C. terminata Dahlbom, 1854
      and C. vanlithi Linsenmaier, 1959. The specific status of C. mediata Linsenmaier,
      1951 and C. solida Haupt, 1957 was not resolved. Included unidentified specimens
      grouped in three clusters, two of which are distinctly delimited and apparently
      represent cryptic species. The specific status of the unidentified samples in the
      third cluster remained unclear. Moreover, our data suggest the existence of
      additional cryptic species currently lumped under the names C. pseudobrevitarsis
      Linsenmaier, 1951 and C. schencki Linsenmaier, 1968. In conclusion, our results
      derived from analysis of mitochondrial loci strongly support the specific status
      of the majority of currently recognised species in the Chrysis ignita species
      group, and suggest the existence of additional cryptic species in Northern
      Europe. Thus, considering the difficulties that often arise during species
      determination based on morphological characters, the mtDNA loci used here appear
      highly suitable for assisting species delimitation in this group as well as
      identification of specimens.  

PMID- 24869540
TI  - Carabid (Coleoptera) type collection at National Forest Insect Collection (NFIC),
      Forest Research Institute, Dehradun (India).
AB  - Members of family Carabidae (Insecta: Coleoptera) are a dominant group of
      terrestrial predators. National Forest Insect Collection (NFIC) of Forest
      Research Institute, Dehradun (India) has a good collection of carabids rich in
      type material. Here we report the details of the type specimens of 139 species
      included in 49 genera, 24 tribes and 14 subfamilies. Colour automontaged
      photographs of each type along with its original labels are also included. 

PMID- 24869541
TI  - The phylogenetic relationships of three new species of the Cyrtodactylus
      pulchellus complex (Squamata: Gekkonidae) from poorly explored regions in
      northeastern Peninsular Malaysia.
AB  - An integrative taxonomic analysis of three newly discovered populations of the
      gekkonid genus Cyrtodactylus Gray from Merapoh, Pahang; Gunung Stong, Kelantan;
      and Gunung Tebu, Terengganu indicate they are part of the C. pulchellus complex
      and each is a new species and thusly named Cyrtodactylus sharkari sp. nov., C.
      jelawangensis sp. nov., and C. timur sp. nov., respectively. Each species bears a
      unique suite of morphological and color pattern characters separating them from
      each other and all other nominal species in the C. pulchellus complex. Their
      phylogenetic relationships to each other and other species in the C. pulchellus
      complex were unexpected in that they are not in accordance with the general
      distribution of the species in this complex, underscoring the intricate
      historical biogeography of the Thai-Malay Peninsula. These descriptions highlight
      our current lack of knowledge concerning the herpetological diversity and
      distribution of species in northeastern Peninsular Malaysia. 

PMID- 24869542
TI  - First fossil occurrence of a filefish (Tetraodontiformes; Monacanthidae) in Asia,
      from the Middle Miocene in Nagano Prefecture, central Japan.
AB  - A new fossil filefish, Aluterus shigensis sp. nov., with a close resemblance to
      the extant Aluterus scriptus (Osbeck), is described from the Middle Miocene
      Bessho Formation in Nagano Prefecture, central Japan. It is characterized by: 21
      total vertebrae; very slender and long first dorsal spine with tiny anterior
      barbs; thin and lancet-shaped basal pterygiophore of the spiny dorsal fin, with
      its ventral margin separated from the skull; proximal tip of moderately slender
      first pterygiophore of the soft dorsal fin not reaching far ventrally; soft
      dorsal-fin base longer than anal-fin base; caudal peduncle having nearly equal
      depth and length; and tiny, fine scales with slender, straight spinules. The
      occurrence of this fossil filefish from the Bessho Formation is consistent with
      the influence of warm water currents suggested by other fossils, but it is
      inconsistent with the deep-water sedimentary environment of this Formation. This
      is the first fossil occurrence of a filefish in Asia; previously described fossil
      filefishes are known from the Pliocene and Pleistocene of Italy, the Pliocene of
      Greece, and the Miocene and Pliocene of North America. These fossil records
      suggest that the genus Aluterus had already been derived and was widely
      distributed during the Middle Miocene with taxa closely resembling Recent
      species. 

PMID- 24869543
TI  - A reappraisal of Notohypshilophodon comodorensis (Ornithischia: Ornithopoda) from
      the Late Cretaceous of Patagonia, Argentina.
AB  - The Bajo Barreal Formation (Cenomanian, Late Cretaceous; central Patagonia,
      Argentina) preserves an important and rich fossil record. Among the dinosaurs
      described, a small ornithischian, Notohypsilophon comodorensis, was named in the
      1990s. This small-bodied dinosaur, the most complete representative of the group
      discovered in that formation, was described as a "hypsilophodontid" ornithopod
      based on close morphological affinities with other members of that group, which
      is currently regarded as paraphyletic. Within this context, we present a restudy
      of Notohypsilophodon. This dinosaur is considered a basal ornithopod, probably
      more basal than Gasparinisaura. Likewise, this analysis emends and provides
      additional unique anatomical characters that support its taxonomic validity and
      position. On the basis of weak evidence, Notohypsilophodon might share the
      presence of gastroliths with other basal ornithopods (Gasparinisaura and Haya),
      which could suggest a specific behavior in response to its food ingestion.
      Finally, this study increases our knowledge of the evolutionary dynamics of South
      American Cretaceous ornithopods, and therefore broadens our knowledge of the
      early Late Cretaceous continental vertebrate assemblages of central Patagonia and
      of the Southern Hemisphere in general.

PMID- 24869544
TI  - Larval masquerade: a new species of paedomorphic salamander (Caudata:
      Plethodontidae: Eurycea) from the Ouachita Mountains of North America.
AB  - Species with truncated developmental patterns may go undetected if they resemble
      the juveniles of their close relatives. Herein we present an example of this
      phenomenon with the description of a highly divergent, relict species of stream
      dwelling plethodontid salamander from the Ouachita Mountains of North America.
      Both mitochondrial and nuclear sequence data show that this new species is most
      closely related to its syntopic relative, Eurycea multiplicata. Interestingly, E.
      multiplicata exhibits the ancestral biphasic (metamorphic) life cycle, whereas
      the new species maintains an aquatic larval form throughout life (paedomorphic)
      and superficially resembles larval E. multiplicata. The new species is the first
      known paedomorphic plethodontid from the Ouachita Mountains, and the most
      divergent paedomorphic salamander discovered in over seventy years. This species
      represents an independent instance of the evolution of paedomorphosis associated
      with a porous streambed, which may facilitate vertical seasonal movements. This
      new species currently has an extremely limited known distribution and is of
      immediate conservation concern. 

PMID- 24869545
TI  - Revision of the acutidens group of Mago (Araneae: Salticidae: Amycinae).
AB  - Of all the amycines, the acutidens group of species of Mago is one of the most
      commonly collected groups throughout the Amazon. Redescriptions of M. acutidens
      Simon and M. longidens Simon by Galiano initially helped separating the two
      species, but then it became clear that we were dealing with a group of several
      similar species demanding revision. In order to make identification possible, we
      present here a revision of this newly proposed group of species, providing
      illustrations of the male palp and epigyne for all the recognized species. The
      female of M. longidens Simon is described for the first time. Besides the new
      records for both M. acutidens and M. longidens, we present M. jurutiensis sp.
      nov. and M. similis sp. nov. from Juruti, Para, Brazil, M. delicatus sp. nov.
      from several localities in the Brazilian states of Amazonas and Para, and M.
      balbina sp. nov. from Presidente Figueiredo, Amazonas. Maps with collecting
      records for all species of the group are presented. 

PMID- 24869546
TI  - The first Amazonian species of Andranthobius Kuschel (Coleoptera: Curculionidae),
      with records of new host palms for the genus.
AB  - Andranthobius setirostris sp. nov. is the first species of Andranthobius Kuschel
      described from the Amazon. It is distinguished from other species within the
      genus by an anterior obtuse tubercle on the lateral margin of the pronotum, the
      rostrum of the males with a lateroventral row of tubercles and comb of setae, and
      a much larger body. Adult specimens were originally collected in flowers of the
      palms Syagrus vermicularis Noblick and Syagrus cocoides Mart., and additional
      collections suggest that this association is specific. Both species of palms are
      recorded for the first time as host plants of Andranthobius. 

PMID- 24869547
TI  - Discovery of a third species of Lamproptera Gray, 1832 (Lepidoptera:
      Papilionidae).
AB  - A newly discovered, third species of the genus Lamproptera (Lepidoptera:
      Papilionidae) is described, 183 years after the second currently recognised
      species was first named. Lamproptera paracurius Hu, Zhang & Cotton sp. n., from
      N.E. Yunnan, China, is based on marked differences in external morphology and
      male genital structure. The species is confirmed as a member of the genus, and
      detailed comparisons are made with other taxa included in the genus. Keys to
      Lamproptera species based on external characters and male genitalia are included.

PMID- 24869548
TI  - A new species, Procloeon monilistylus sp. n. (Ephemeroptera, Baetidae), from the
      Russian Far East.
AB  - A new, two-winged species Procloeon monilistylus sp. n. is described from the
      Russian Far East based on male and female imagoes reared from larvae. The larva
      differs from other species of Procloeon by having a deeply separated incisor and
      kinetodontium of the mandibles. The imago differs from all Baetidae (and mayflies
      in general) by the shape of the gonostyli. Formerly this species was known as
      "Cloeon (Centroptilum) sp. 1" sensu Kluge & Novikova 1992. 

PMID- 24869549
TI  - New taxa, notes and new synonymy in Neoibidionini (Cerambycidae, Coleoptera).
AB  - New taxa, notes, and new synonymy in Neoibidionini (Cerambycidae, Coleoptera) are
      given. New taxa are described from Ecuador: Compsibidion inflatum sp. nov.,
      Bezarkia gen. nov. and B. suturalis sp. nov., Corimbion antennatum sp. nov. and
      Neocompsa muira sp. nov.; from Mexico: Neocompsa chiapensis sp. nov., and from
      French Guyana: Kunaibidion giesberti sp. nov. Pygmodeon maculatum Martins &
      Galileo, 2012 is considered a new synonym of Heterachthes xyleus Martins, 1974
      which is transferred to the genus Pygmodeon as a new combination. Notes on
      variability and new records of Asynapteron equatorianum (Martins, 1960) are
      presented. 

PMID- 24869550
TI  - The advertisement call of the Cape Melville Treefrog Litoria andiirrmalin (Anura:
      Hylidae).

PMID- 24869551
TI  - Relicts from Tertiary Australasia: undescribed families and subfamilies of
      songbirds (Passeriformes) and their zoogeographic signal.
AB  - A number of hitherto unrecognized, deeply divergent taxa of Australasian
      songbirds have been revealed by DNA sequence studies in the last decade.
      Differentiation among them is at levels equivalent to family and subfamily rank
      among songbirds generally. Accordingly, the purpose of this paper is to name and
      describe eleven of them formally under Articles 13.1, 13.2, 16.1 and 16.2 of the
      International Code of Zoological Nomenclature so that they are made available for
      use in zoology. The taxa are: families Oreoicidae, Eulacestomatidae,
      Rhagologidae, Ifritidae and Melampittidae, and subfamilies Pachycareinae,
      Oreoscopinae, Toxorhamphinae, Oedistomatinae, Peltopsinae and Lamproliinae. The
      families to which the subfamilies belong are documented. Morphological and
      behavioural traits of the new family-group taxa are discussed; reasons for
      taxonomic rankings are summarized; and grounds for the geographic origin of
      corvoid songbirds, to which all the new families belong, are briefly addressed.
      One new genus,Megalampitta in Melampittidae, is also described. 

PMID- 24869553
TI  - Aquatic Empididae (Diptera: Hemerodromiinae and Clinocerinae) of the Sierra
      Nevada, Spain, with the description of five new species .
AB  - In total 24 species of aquatic Empididae (Clinocerinae and Hemerodromiinae) are
      known from the Sierra Nevada Mountains of Spain, including five new species
      (Hemerodromia planti Ivkovic & Sinclair sp. nov., Kowarzia nevadensis Sinclair &
      Ivkovic sp. nov., Wiedemannia darioi Sinclair & Ivkovic sp. nov., W. horvati
      Ivkovic & Sinclair sp. nov. and W. vedranae Ivkovic & Sinclair sp. nov.). The new
      species are described, illustrated and distribution of all species listed.
      Wiedemannia (Philolutra) angelieri Vaillant and W. (Roederella) ouedorum Vaillant
      are newly recorded in Sierra Nevada and nine species are endemic to this region.
      A key to all 24 species of aquatic empidids is presented. 

PMID- 24869552
TI  - Ectopsocidae (Psocodea: 'Psocoptera') from Valle del Cauca and NNP Gorgona,
      Colombia.
AB  - The results of a survey of the psocid family Ectopsocidae in Valle del Cauca and
      NNP Gorgona, are here presented. Fifteen species were identified, in the genera
      Ectopsocus (14 species), and Ectopsocopsis (one species); four of the Ectopsocus
      species are new to science and are here described and illustrated. The male of E.
      thorntoni Garcia Aldrete is here described. Records of Ectopsocopsis cryptomeriae
      (Enderlein), Ectopsocus briggsi McLachlan, E. californicus Banks, E. columbianus
      Badonnel, E. maindroni Badonnel, E. meridionalis Ribaga, E. pilosus Badonnel, E.
      richardsi Pearman, E. titschacki Jentsch, and E. vilhenai Badonnel, are provided.
      Ten species were found only in Valle del Cauca, two species were found only in
      the NNP Gorgona, and three species were found at both sites. The specimens
      studied are deposited in the Entomological Museum, Universidad del Valle,
      Santiago de Cali, Colombia (MUSENUV). 

PMID- 24869554
TI  - On the systematics of Trimeresurus labialis Fitzinger in Steindachner, 1867, a
      pitviper from the Nicobar Islands (India), with revalidation of Trimeresurus
      mutabilis Stoliczka, 1870 (Squamata, Viperidae, Crotalinae).
AB  - The Asian pitviper currently identified as Trimeresurus labialis Fitzinger in
      Steindachner, 1867 is revised on the basis of morphological data obtained from 37
      preserved specimens originating from seven islands of the Nicobar Islands.
      Multivariate analyses shows that these specimens can be divided into two clusters
      of populations which differ by a series of constant taxonomically informative
      morphological characters. The first cluster, which includes the name-bearing
      types of Trimeresurus labialis Fitzinger in Steindachner, 1867, is present only
      on Car Nicobar Island. The second cluster, which includes the name-bearing types
      of Trimeresurus mutabilis Stoliczka, 1870, is distributed on the Central Nicobar
      Islands. We regard these clusters as distinct species, which are morphologically
      diagnosable and isolated from each other. As a consequence, Trimeresurus
      mutabilis, long considered a synonym of T. labialis, is here resurrected to
      specific level. A lectotype is designated for Trimeresurus mutabilis. 

PMID- 24869555
TI  - Two new species of Caenohalictus Cameron, 1903 (Hymenoptera: Halictidae) from
      Colombia.
AB  - This paper describes and illustrates females and males of two species of
      Caenohalictus Cameron, 1903: C. sabanaensis n.sp. and C. alexandrei n.sp. Both
      species are commonly collected in the Savanna of Bogota, a high plateau in the
      central region of the Eastern Andes of Colombia. Notes on morphological
      variations within and among the species, as well as comments on some biological
      aspects and images of diagnostic structures are provided. 

PMID- 24869556
TI  - Rediscovery of Lophiodes triradiatus (Lloyd, 1909), a senior synonym of L.
      infrabrunneus Smith and Radcliffe (Lophiiformes: Lophiidae).
AB  - Examination of the holotype and three recently collected additional specimens
      from the Indian Ocean has revealed that Lophius triradiatus Lloyd, 1909 (now
      under Lophiodes)  is a valid species and a senior synonym of Lophiodes
      infrabrunneus Smith & Radcliffe, 1912 and Lophiodes abdituspinus Ni, Wu & Li,
      1990. A detailed description of the additional specimens is provided. 

PMID- 24869557
TI  - A new species of Neotraginops Prado (Diptera: Odiniidae) from Mexico and Belize,
      with additional records for Odinia coronata Sabrosky in Mesoamerica.
AB  - Neotraginops mexicanus n. sp. is described and illustrated based on specimens
      from Mexico and Belize, representing the second known species for the genus.
      Additional records for Odinia coronata Sabrosky from Mexico and Nicaragua are
      provided. 

PMID- 24869559
TI  - The chemistry of transition metals with three-membered ring heterocycles.

PMID- 24869560
TI  - What is the importance of classifying Aspergillus disease in cystic fibrosis
      patients?
AB  - Aspergillus species are commonly isolated from lower respiratory tract samples of
      patients with cystic fibrosis (CF) and markers of immunological sensation to
      Aspergillus are frequently encountered in this group of patients; however, the
      contribution of Aspergillus to CF lung disease outside of the typical
      complications of ABPA and aspergilloma formation remains largely unclear.
      Patients with CF show discretely different responses to Aspergillus, though the
      underlying reasons for this variation are unknown. Recent work has begun to allow
      us to categorize patient responses to Aspergillus based upon molecular markers of
      infection and immune sensitization. Aspergillus sensitization and/or airway
      infection is associated with worse FEV1, in CF and other patients (asthma,
      chronic obstructive pulmonary disease, bronchiectasis). Classification of
      different clinical phenotypes of Aspergillus will enable future studies to
      determine the natural history of different manifestations of Aspergillus disease
      and evaluate the effects of intervention with antifungal therapy. 

PMID- 24869561
TI  - Controlled translocation of palladium(II) within a 22 ring atom macrocyclic
      ligand.
AB  - Double aza-Michael addition of n-butylamine to the two acrylamide groups of
      acyclic N(2),N(6)-bis(6-acrylamidopyridin-2-yl)pyridine-2,6-dicarboxamide gives
      the corresponding macrocycle, H4L. H4L has potential coordination pockets
      associated with the 2,6-dicarboxamide (head) and the butylamine (tail) regions of
      the macrocycle. Depending on the conditions employed, macrocyclic complexes with
      palladium(II) coordinated to either the tail or the head of the macrocycle can be
      isolated. Thus, treatment of H4L with [PdCl2(NCPh)2] and sodium acetate, or
      [Pd(OAc)2] gives the closely related "tail-coordinated" complexes [PdCl(H3L)]
      (3a) or [Pd(OAc)(H3L)] (3b), respectively. However, employment of the bases 1,8
      diazabicyclo[5.4.0]undec-7-ene (DBU) or pyridine during the treatment of H4L with
      [Pd(OAc)2] results in the "head-coordinated" complexes [Pd(NH2R)(H2L)] (NH2R = N
      (3-aminopropyl)caprolactam, which is formed by hydrolysis of DBU) (5) or
      [Pd(OH2)(H2L)] (6), respectively. Translocation of the palladium ion from the
      macrocycle tail in 3b to the head occurs on treatment with either DBU or N-(3
      aminopropyl)caprolactam. In both cases the product 5 is formed. The aqua ligand
      in 6 is labile and easily displaced by the N-donor ligands n-butylamine, N-(3
      aminopropyl)caprolactam or DBU to give the corresponding complexes
      [Pd(NH2(n)Bu)(H2L)] (4), (5), or [Pd(DBU)(H2L)] (7). The data suggest that
      hydrolysis of DBU to produce the N-(3-aminopropyl)caprolactam ligand in 5 is
      catalysed by the acetic acid formed during ligand metallation rather than by
      coordination to palladium. The X-ray crystal structures of H4L, 5, and 6 are
      reported.

PMID- 24869562
TI  - Building on nursing's legacy.

PMID- 24869563
TI  - Mental illness myths.

PMID- 24869564
TI  - RN staffing.

PMID- 24869565
TI  - On writing.

PMID- 24869566
TI  - Whatever happened to the clinical DNP?
AB  - Are current doctor of nursing practice programs a good fit for NPs in direct
      patient care? 

PMID- 24869569
TI  - Health care reform expands many services for women.
AB  - Restrictions and controversy continue to surround some preventive care services. 

PMID- 24869573
TI  - Not getting through: vaccination message is ineffective.
AB  - Scare tactics can backfire; subtler messaging might be more useful. 

PMID- 24869570
TI  - Don't limit APRNs, says the FTC.
AB  - More marketplace competition can lower costs and improve the quality of care. 

PMID- 24869576
TI  - Fight the fakes.

PMID- 24869577
TI  - Are you financially prepared for retirement?
AB  - Many nurses aren't, but it's never too late to start saving. 

PMID- 24869579
TI  - New approved indication for ibrutinib.

PMID- 24869580
TI  - Effective and safe analgesia for forceps delivery.
AB  - This is a summary of a nursing care-related systematic review from the Cochrane
      Library.

PMID- 24869584
TI  - JBI's Systematic Reviews: Study selection and critical appraisal.
AB  - This article is the fourth in a series on the systematic review from the Joanna
      Briggs Institute, an international collaborative supporting evidence-based
      practice in nursing, medicine, and allied health fields. The purpose of the
      series is to describe how to conduct a systematic review-one step at a time. This
      article focuses on the study selection and critical appraisal steps in the
      process. These steps ensure that the review produces valid results capable of
      providing a useful basis for informing policy, clinical practice, and future
      research. 

PMID- 24869589
TI  - The ethics of denying smokers employment in health care.
AB  - Such policies send a powerful message, but are the underlying assumptions
      defensible? 

PMID- 24869591
TI  - Multicultural web resources.
AB  - To assist nurses in providing culturally acceptable care. 

PMID- 24869590
TI  - Developing new nursing leaders.
AB  - This is the fourth article in a series on leadership, coordinated by the American
      Organization of Nurse Executives (AONE), highlighting topics of interest to nurse
      managers and emerging nurse leaders. The AONE provides leadership, professional
      development, advocacy, and research to advance nursing practice and patient care,
      promote nursing leadership excellence, and shape public policy for health care. 

PMID- 24869592
TI  - Treating depression with transcranial direct current stimulation.
AB  - When medication is not enough-will this experimental treatment present a cure? 

PMID- 24869593
TI  - Making it fit.
AB  - A new NP on a psych unit finds her professional identity must be redefined. 

PMID- 24869595
TI  - Clinicians' involvement in capital punishment--constitutional implications.

PMID- 24869594
TI  - Juzen-Taiho-to, an herbal medicine, promotes the differentiation of transplanted
      bone marrow cells into microglia in the mouse brain injected with fibrillar
      amyloid beta.
AB  - Microglia are the main immunocompetent and phagocytic cells in Alzheimer's
      disease (AD). Bone marrow-derived microglia have been demonstrated to be more
      effective in antigen presentation and phagocytosis than inherent microglia in AD.
      Thus, microglia have received much attention in the pathogenesis of AD. The
      herbal medicine Juzen-taiho-to (JTT) has been reported to reduce beta-amyloid
      (Abeta) burden in the mouse brain of an AD model. In this study, we explored the
      effects of JTT on the migration and differentiation of bone marrow-derived cells
      in the mouse brain of acutely induced AD. To chase bone marrow-derived cells, we
      made a chimeric mouse line in C57BL/6 by transplanting fresh bone marrow cells,
      isolated from the transgenic mice expressing enhanced green fluorescent protein
      gene. The chimeric mice were orally administrated with JTT or distilled water,
      and were left untreated or given intrahippocampal injection of fibrillar Abeta 1
      42 (fAbeta42) or vehicle. In the hippocampus of the vehicle-injected mouse, JTT
      treatment for 37 days caused a significant increase in the number of microglial
      cells. In the fAbeta42-injected mouse hippocampus, a larger number of bone marrow
      derived cells were detected in JTT-treated mice than control mice in the non
      neighboring regions of the fAbeta42-injected site but not around the injected
      site. These results suggest that JTT might contribute to the reduction of Abeta
      burden and the immune surveillance in non-pathological as well as pathological
      brain regions. The results also implicate the therapeutic potential of JTT in AD.

PMID- 24869596
TI  - Caution advised: Medicare's physician-payment data release.

PMID- 24869597
TI  - Ibrutinib resistance in chronic lymphocytic leukemia.

PMID- 24869599
TI  - The Medicare physician-data release--context and rationale.

PMID- 24869600
TI  - Mechanism of strain-influenced quantum well thickness reduction in GaN/AlN short
      period superlattices.
AB  - We report on the mechanism of strain-influenced quantum well (QW) thickness
      reduction in GaN/AlN short-period superlattices grown by plasma-assisted
      molecular beam epitaxy. Density functional theory was used to support the idea of
      a thermally activated exchange mechanism between Al adatoms and Ga surface atoms
      that is influenced by the strain state of the GaN QWs. These ab initio
      calculations support our experimentally observed reduction in QW thickness for
      different intrinsic strains. 

PMID- 24869601
TI  - Meta-analysis of efficacy and safety of the new anticoagulants versus warfarin in
      patients with atrial fibrillation.
AB  - OBJECTIVE: To assess the efficacy and safety of the new oral anticoagulants
      versus warfarin in patients with atrial fibrillation by the meta-analyses
      performed for 5 studies ARISTOTLE, ENGAGE AF-TIMI 48, RE-LY, ROCKET-AF, and J
      ROCKET. METHODS: The events including primary efficacy endpoint (stroke and
      systemic embolism), ischemic stroke, hemorrhagic stroke, all-cause mortality, and
      myocardial infarction were used for efficacy analysis and those including major
      bleeding, intracranial hemorrhage, and gastrointestinal bleeding were used for
      safety analysis. Instead of combining both doses to 1 meta-analysis, the high
      dose groups of RE-LY (150 mg twice daily) and ENGAGE AF-TIMI 48 (60 mg twice
      daily) were combined with the single dose studies ARISTOTLE, ROCKET-AF, and J
      ROCKET. A separate meta-analysis was done for the low-dose groups of RE-LY (110
      mg twice daily) and ENGAGE AF-TIMI 48 (30 mg twice daily). RESULTS: The high-dose
      regimen had better performance than low dose in efficacy. In addition, low-dose
      regimen demonstrated to significantly reduce the risk of hemorrhagic stroke, all
      cause mortality, and intracranial hemorrhage. CONCLUSIONS: The new oral
      anticoagulants demonstrated promising alternatives to warfarin in prevention of
      stroke in patients with atrial fibrillation.

PMID- 24869598
TI  - Resistance mechanisms for the Bruton's tyrosine kinase inhibitor ibrutinib.
AB  - BACKGROUND: Ibrutinib is an irreversible inhibitor of Bruton's tyrosine kinase
      (BTK) and is effective in chronic lymphocytic leukemia (CLL). Resistance to
      irreversible kinase inhibitors and resistance associated with BTK inhibition have
      not been characterized. Although only a small proportion of patients have had a
      relapse during ibrutinib therapy, an understanding of resistance mechanisms is
      important. We evaluated patients with relapsed disease to identify mutations that
      may mediate ibrutinib resistance. METHODS: We performed whole-exome sequencing at
      baseline and the time of relapse on samples from six patients with acquired
      resistance to ibrutinib therapy. We then performed functional analysis of
      identified mutations. In addition, we performed Ion Torrent sequencing for
      identified resistance mutations on samples from nine patients with prolonged
      lymphocytosis. RESULTS: We identified a cysteine-to-serine mutation in BTK at the
      binding site of ibrutinib in five patients and identified three distinct
      mutations in PLCgamma2 in two patients. Functional analysis showed that the C481S
      mutation of BTK results in a protein that is only reversibly inhibited by
      ibrutinib. The R665W and L845F mutations in PLCgamma2 are both potentially gain
      of-function mutations that lead to autonomous B-cell-receptor activity. These
      mutations were not found in any of the patients with prolonged lymphocytosis who
      were taking ibrutinib. CONCLUSIONS: Resistance to the irreversible BTK inhibitor
      ibrutinib often involves mutation of a cysteine residue where ibrutinib binding
      occurs. This finding, combined with two additional mutations in PLCgamma2 that
      are immediately downstream of BTK, underscores the importance of the B-cell
      receptor pathway in the mechanism of action of ibrutinib in CLL. (Funded by the
      National Cancer Institute and others.).

PMID- 24869602
TI  - Choosing wisely (and carefully) Canada.

PMID- 24869604
TI  - Review of a medical student-run surgery lecture series and skills lab curriculum.
AB  - Evidence suggests that early exposure to surgical techniques, surgical knowledge
      and mentors strongly correlates with students' interest, knowledge and confidence
      in general surgery as a postgraduate career choice. Preclerkship exposure to
      surgery and implementation of a formal surgical curriculum is often restricted
      owing to attending surgeon time commitments and cost limitations. To promote
      earlier exposure to surgery, a group of senior medical students at McMaster
      University, Hamilton, Ont., developed and implemented a novel pilot program with
      a surgical lecture series and a surgical skills laboratory for preclerkship
      students. This commentary discusses the effectiveness of these initiatives.

PMID- 24869605
TI  - Single incision laparoscopic surgery in Canadian children.
AB  - As minimally invasive surgery progresses, there have been attempts to modify the
      technique to minimize both the number and visibility of incisions. These newer
      techniques are known by multiple acronyms, including single incision laparoscopic
      surgery (SILS). The SILS technique has gained popularity in the United States,
      particularly owing to its perceived improved cosmesis. The SILS technique has
      been primarily used in adults, and the number of pediatric publications on the
      topic is underwhelming. We have begun to evaluate SILS at our centre to determine
      its applicability in both a Canadian and pediatric practice, and this commentary
      discusses our initial application of the procedure.

PMID- 24869606
TI  - Factors affecting the relative age effect in NHL athletes.
AB  - BACKGROUND: The relative age effect (RAE) has been reported for a number of
      different activities. The RAE is the phenomena whereby players born in the first
      few months of a competition year are advantaged for selection to elite sports.
      Much of the literature has identified elite male athletics, such as the National
      Hockey League (NHL), as having consistently large RAEs. We propose that RAE may
      be lessened in the NHL since the last examination. METHODS: We examined
      demographic and selection factors to understand current NHL selection biases.
      RESULTS: We found that RAE was weak and was only evident when birth dates were
      broken into year halves. Players born in the first half of the year were
      relatively advantaged for entry into the NHL. We found that the RAE is smaller
      than reported in previous studies. Intraplayer comparisons for multiple factors,
      including place of birth, country of play, type of hockey played, height and
      weight, revealed no differences. Players who were not drafted (e.g., free agents)
      or who played university hockey in North America had no apparent RAE. CONCLUSION:
      We found little evidence of an RAE in the current NHL player rosters. A larger
      study of all Canadian minor hockey intercity teams could help determine the
      existence of an RAE.

PMID- 24869607
TI  - Does ultrasonography accurately diagnose acute cholecystitis? Improving
      diagnostic accuracy based on a review at a regional hospital.
AB  - BACKGROUND: Acute cholecystitis is one of the most common diseases requiring
      emergency surgery. Ultrasonography is an accurate test for cholelithiasis but has
      a high false-negative rate for acute cholecystitis. The Murphy sign and
      laboratory tests performed independently are also not particularly accurate. This
      study was designed to review the accuracy of ultrasonography for diagnosing acute
      cholecystitis in a regional hospital. METHODS: We studied all emergency
      cholecystectomies performed over a 1-year period. All imaging studies were
      reviewed by a single radiologist, and all pathology was reviewed by a single
      pathologist. The reviewers were blinded to each other's results. RESULTS: A total
      of 107 patients required an emergency cholecystectomy in the study period; 83 of
      them underwent ultrasonography. Interradiologist agreement was 92% for
      ultrasonography. For cholelithiasis, ultrasonography had 100% sensitivity, 18%
      specificity, 81% positive predictive value (PPV) and 100% negative predictive
      value (NPV). For acute cholecystitis, it had 54% sensitivity, 81% specificity,
      85% PPV and 47% NPV. All patients had chronic cholecystitis and 67% had acute
      cholecystitis on histology. When combined with positive Murphy sign and elevated
      neutrophil count, an ultrasound showing cholelithiasis or acute cholecystitis
      yielded a sensitivity of 74%, specificity of 62%, PPV of 80% and NPV of 53% for
      the diagnosis of acute cholecystitis. CONCLUSION: Ultrasonography alone has a
      high rate of false-negative studies for acute cholecystitis. However, a higher
      rate of accurate diagnosis can be achieved using a triad of positive Murphy sign,
      elevated neutrophil count and an ultrasound showing cholelithiasis or
      cholecystitis.

PMID- 24869608
TI  - Minimally displaced clavicle fracture after high-energy injury: are they likely
      to displace?
AB  - BACKGROUND: Nondisplaced or minimally displaced clavicle fractures are often
      considered to be benign injuries. These fractures in the trauma patient
      population, however, may deserve closer follow-up than their low-energy
      counterparts. We sought to determine the initial assessment performed on these
      patients and the rate of subsequent fracture displacement in patients sustaining
      high-energy trauma when a supine chest radiograph on initial trauma survey
      revealed a well-aligned clavicle fracture. METHODS: We retrospectively reviewed
      the cases of trauma alert patients who sustained a midshaft clavicle fracture
      (AO/OTA type 15-B) with less than 100% displacement treated at a single level 1
      trauma centre between 2005 and 2010. We compared fracture displacement on initial
      supine chest radiographs and follow-up radiographs. Orthopedic consultation and
      the type of imaging studies obtained were also recorded. RESULTS: Ninety-five
      patients with clavicle fractures met the inclusion criteria. On follow-up, 57
      (60.0%) had displacement of 100% or more of the shaft width. Most patients
      (63.2%) in our study had an orthopedic consultation during their hospital
      admission, and 27.4% had clavicle radiographs taken on the day of admission.
      CONCLUSION: Clavicle fractures in patients with a high-energy mechanism of injury
      are prone to fracture displacement, even when initial supine chest radiographs
      show nondisplacement. We recommend clavicle films as part of the initial
      evaluation for all patients with clavicle fractures and early follow-up within
      the first 2 weeks of injury.

PMID- 24869609
TI  - Intraoperative systemic lidocaine for pre-emptive analgesics in subtotal
      gastrectomy: a prospective, randomized, double-blind, placebo-controlled study.
AB  - BACKGROUND: Pre-emptive intravenous lidocaine infusion is known to improve
      postoperative pain in abdominal surgery. We assessed the effect of intravenous
      lidocaine infusion in patients who underwent subtotal gastrectomy. METHODS: We
      conducted a double-blind, placebo-controlled study with patients undergoing
      subtotal gastrectomy for early gastric cancer divided into 2 groups: 1 group
      received intravenous lidocaine infusion preoperatively and throughout surgery,
      and the other received normal saline infusion (placebo). We assessed
      postoperative outcomes, including pain scores on a visual analogue scale (VAS),
      administration frequency of patient-controlled analgesia (PCA) and the amount of
      consumed fentanyl. Postoperative nausea and vomiting, length of hospital stay
      (LOS), time to return to regular diet and patient satisfaction at discharge were
      evaluated. RESULTS: There were 36 patients in our study. Demographic
      characteristics were similar between the groups. The VAS pain scores and
      administration frequency of PCA were significantly lower in the lidocaine group
      until 24 hours after surgery, and fentanyl consumption was significantly lower in
      this group until 12 hours postoperatively compared with the placebo group. The
      total amount of consumed fentanyl and the total administration frequency of PCA
      were significantly lower in the lidocaine than the control group. No significant
      differences were detected in terms of nausea and vomiting, return to regular
      diet, LOS and patient satisfaction, and there were no reported side-effects of
      lidocaine. CONCLUSION: Intravenous lidocaine infusion reduces pain during the
      postoperative period after subtotal gastrectomy.

PMID- 24869610
TI  - The effects on oxidative DNA damage of laparoscopic gastric band applications in
      morbidly obese patients.
AB  - BACKGROUND: Obesity may induce oxidative stress, causing oxidative damage of DNA.
      We examined associations between decreasing serum and urinary 8-hydroxy-2'
      deoxyguanosine (8-OHdG) levels and weight loss in morbidly obese patients before
      and 6 months after laparoscopic adjustable gastric banding (LAGB). METHODS: We
      compared patients who had surgery for morbid obesity with healthy, nonobese
      controls. Urine and fasting blood samples were collected once from the controls
      and from the morbidly obese patients before and 6 months after the LAGB. The
      serum and urinary 8-OHdG levels were evaluated in these groups using an enzyme
      linked immunosorbent assay kit. RESULTS: We included 20 patients who had surgery
      for morbid obesity (8 men, 12 women, mean body mass index [BMI] 46.82 +/- 4.47)
      and 20 healthy, nonobese people (10 men, 10 women, mean BMI 22.52 +/- 2.08) in
      our study. There was no significant difference in serum 8-OHdG levels between the
      groups, whereas urinary 8- OHdG levels were significantly higher in morbidly
      obese patients than in controls. Weight, BMI and serum and urinary 8-OHdG levels
      were significantly decreased in morbidly obese patients 6 months after LAGB.
      CONCLUSION: The LAGB provides efficient weight loss in patients with morbid
      obesity. The systemic oxidative DNA damage was increased by the morbid obesity,
      but this increase was not related to weight gain, and it was more evident in
      serum than urine samples. After LAGB for morbid obesity, the oxidative DNA damage
      declined both in serum and urine.

PMID- 24869611
TI  - A comparison of the modified Tokuhashi and Tomita scores in determining prognosis
      for patients afflicted with spinal metastasis.
AB  - BACKGROUND: The prognosis of patients with spinal metastasis is not very
      promising and hard to predict. It is for this reason that scoring systems, such
      as the modified Tokuhashi and Tomita scores, have been created. We sought to
      determine the effectiveness of these scores in predicting patient survival.
      METHODS: We retrospectively reviewed the data of all patients treated for spinal
      metastasis between March 2003 and March 2012 in our centre. We computed the
      Tokuhashi and Tomita scores and compared them with documented patient survival.
      The 2 scores were also compared with one another. RESULTS: We identified 128
      patients with spinal metastasis. The average survival of patients with predicted
      poor, average and good prognosis was 5, 17 and 25 months, respectively for the
      modified Tokuhashi score and 3, 16 and 19 months, respectively, for the Tomita
      score. Poor, average and good prognosis predictions differed significantly from
      one another for all 3 categories for the Tokuhashi score (all p < 0.05). There
      was no significant difference in the moderate and good prognoses for the Tomita
      score (p = 0.15). When comparing both scores, we obtained a weighted kappa of
      0.4489 (standard deviation 0.0568, 95% confidence interval 0.3376-0.5602),
      demonstrating moderate agreement between scores. CONCLUSION: Both scores have
      merit for use in a clinical setting and can be used as tools to help determine
      treatment choice. The modified Tokuhashi score had better accuracy in determining
      actual survival.

PMID- 24869612
TI  - The impact of an acute care surgery clinical care pathway for suspected
      appendicitis on the use of CT in the emergency department.
AB  - BACKGROUND: The natural evolution of an acute care surgery (ACS) service is to
      develop disease-specific care pathways aimed at quality improvement. Our primary
      goal was to evaluate the implementation of an ACS pathway dedicated to suspected
      appendicitis on patient flow and the use of computed tomography (CT) in the
      emergency department (ED). METHODS: All adults within a large health care system
      (3 hospitals) with suspected appendicitis were analyzed during our study period,
      which included 3 time periods: pre- and postimplementation of the disease
      specific pathway and at 12-month follow-up. RESULTS: Of the 1168 consultations
      for appendicitis that took place during our study period, 349 occurred
      preimplementation, 392 occurred postimplementation, and 427 were follow-up
      visits. In all, 877 (75%) patients were admitted to the ACS service. Overall, 83%
      of patients underwent surgery within 6 hours. The mean wait time from CT request
      to obtaining the CT scan decreased with pathway implementation at all sites (197
      v. 143 min, p < 0.001). This improvement was sustained at 12-month followup (131
      min, p < 0.001). The pathway increased the number of CTs completed in under 2
      hours from 3% to 42% (p < 0.001). No decrease in the total number of CTs or the
      pattern of ultrasonography was noted (p = 0.42). Wait times from ED triage to
      surgery were shortened (665 min preimplementation, 633 min postimplementation,
      631 min at the 12-month follow-up, p = 0.040). CONCLUSION: A clinical care
      pathway dedicated to suspected appendicitis can decrease times to both CT scan
      and surgical intervention.

PMID- 24869614
TI  - Outcomes following surgical treatment of periprosthetic femur fractures: a single
      centre series.
AB  - BACKGROUND: Periprosthetic femoral fracture after total hip arthroplasty (THA) is
      an increasing clinical problem and a challenging complication to treat
      surgically. The aim of this retrospective study was to review the treatment of
      periprosthetic fractures and the complication rate associated with treatment at
      our institution. METHODS: We reviewed the cases of patients with periprosthetic
      femoral fractures treated between January 2004 and June 2009. We used the
      Vancouver classification to assess fracture types, and we identified the surgical
      interventions used for these fracture types and the associated complications.
      RESULTS: We treated 45 patients with periprosthetic femoral fractures during the
      study period (15 men, 30 women, mean age 78 yr). Based on Vancouver
      classification, 2 patients had AL fractures, 9 had AG, 15 had B1, 24 had B2, 2
      had B3 and 4 had C fractures. Overall, 82% of fractures united with a mean time
      to union of 15 (range 2-64) months. Fourteen patients (31%) had complications; 11
      of them had a reoperation: 6 to treat an infection, 6 for nonunion and 2 for
      aseptic femoral component loosening. CONCLUSION: Periprosthetic fractures are
      difficult to manage. Careful preoperative planning and appropriate intraoperative
      management in the hands of experienced surgeons may increase the chances of
      successful treatment. However, patients should be counselled on the high risk of
      complications when presenting with this problem.

PMID- 24869613
TI  - Differences in telomerase activity between colon and rectal cancer.
AB  - BACKGROUND: Colorectal cancer is one of the most common cancers and the third
      leading cause of cancer death in both sexes. The disease progresses as a
      multistep process and is associated with genetic alterations. One of the
      characteristic features of cancer is telomerase activation. We sought to evaluate
      the differences in telomerase activity between colon cancer and adjacent normal
      tissue and to correlate the differences in telomerase activity between different
      locations with clinicopathological factors and survival. METHODS: Matched colon
      tumour samples and adjacent normal mucosa samples 10 cm away from the tumour were
      collected during colectomy. We assessed telomerase activity using real time
      polymerase chain reaction. Several pathological characteristics of tumours,
      including p53, Ki-67, p21, bcl2 and MLH1 expression were also studied. RESULTS:
      We collected samples from 49 patients. There was a significantly higher
      telomerase activity in colon cancer tissue than normal tissue. Adenocarcinomas of
      the right colon express significantly higher telomerase than left-side cancers.
      Colon cancers and their adjacent normal tissue had significantly more telomerase
      and were more positive to MLH1 than rectal cancers. The expression of p53
      negatively correlated to telomerase activity and was linked to better patient
      survival. CONCLUSION: Colon and rectal cancers seem to have different telomerase
      and MLH1 profiles, and this could be another factor for their different biologic
      and clinical behaviour and progression. These results support the idea that the
      large bowel cannot be considered a uniform organ, at least in the biology of
      cancer.

PMID- 24869615
TI  - CAGS and ACS evidence based reviews in surgery. Is a diverting loop ileostomy and
      colonic lavage an alternative to colectomy for the treatment of severe
      Clostridium difficile-associated disease?
AB  - The term "evidence-based medicine" was first coined by Sackett and colleagues as
      "the conscientious, explicit and judicious use of current best evidence in making
      decisions about the care of individual patients."1 The key to practising
      evidencebased medicine is applying the best current knowledge to decisions in
      individual patients. Medical knowledge is continually and rapidly expanding. For
      clinicians to practise evidence-based medicine, they must have the skills to read
      and interpret the medical literature so that they can determine the validity,
      reliability, credibility and utility of individual articles. These skills are
      known as critical appraisal skills, and they require some knowledge of
      biostatistics, clinical epidemiology, decision analysis and economics, and
      clinical knowledge. Evidence Based Reviews in Surgery (EBRS) is a program jointly
      sponsored by the Canadian Association of General Surgeons (CAGS) and the American
      College of Surgeons (ACS). The primary objective of EBRS is to help practising
      surgeons improve their critical appraisal skills. During the academic year, 8
      clinical articles are chosen for review and discussion. They are selected for
      their clinical relevance to general surgeons and because they cover a spectrum of
      issues im -port ant to surgeons, including causation or risk factors for disease,
      natural history or prognosis of disease, how to quantify disease, diagnostic
      tests, early diagnosis and the effectiveness of treatment. A methodological
      article guides the reader in critical appraisal of the clinical article.
      Methodological and clinical reviews of the article are performed by experts in
      the relevant areas and posted on the EBRS website, where they are archived
      indefinitely. In addition, a listserv allows participants to discuss the monthly
      article. Surgeons who participate in the monthly packages can obtain Royal
      College of Physicians and Surgeons of Canada Maintenance of Certification credits
      and/or continuing medical education credits for the current article only by
      reading the monthly articles, participating in the listserv discussion, reading
      the methodological and clinical reviews and completing the monthly online
      evaluation and multiple choice questions. We hope readers will find EBRS useful
      in improving their critical appraisal skills and in keeping abreast of new
      developments in general surgery. Four reviews are published in condensed versions
      in the Canadian Journal of Surgery, 4 are published in the Journal of the
      American College of Surgeons and 4 are published in Diseases of the Colon and
      Rectum. For further information about EBRS, please refer to the CAGS or ACS
      websites. Questions and comments can be directed to the program administrator,
      Marg McKenzie, at mmckenzie@mtsinai.on.ca.

PMID- 24869616
TI  - Low-intensity pulsed ultrasonography versus electrical stimulation for fracture
      healing: a systematic review and network meta-analysis.
AB  - BACKGROUND: To best inform evidence-based patient care, it is often desirable to
      compare competing therapies. We performed a network meta-analysis to indirectly
      compare low intensity pulsed ultrasonography (LIPUS) with electrical stimulation
      (ESTIM) for fracture healing. METHODS: We searched the reference lists of recent
      reviews evaluating LIPUS and ESTIM that included studies published up to 2011
      from 4 electronic databases. We updated the searches of all electronic databases
      up to April 2012. Eligible trials were those that included patients with a fresh
      fracture or an existing delayed union or nonunion who were randomized to LIPUS or
      ESTIM as well as a control group. Two pairs of reviewers, independently and in
      duplicate, screened titles and abstracts, reviewed the full text of potentially
      eligible articles, extracted data and assessed study quality. We used standard
      and network meta-analytic techniques to synthesize the data. RESULTS: Of the 27
      eligible trials, 15 provided data for our analyses. In patients with a fresh
      fracture, there was a suggested benefit of LIPUS at 6 months (risk ratio [RR]
      1.17, 95% confidence interval [CI] 0.97-1.41). In patients with an existing
      nonunion or delayed union, ESTIM had a suggested benefit over standard care on
      union rates at 3 months (RR 2.05, 95% CI 0.99-4.24). We found very low-quality
      evidence suggesting a potential benefit of LIPUS versus ESTIM in improving union
      rates at 6 months (RR 0.76, 95% CI 0.58-1.01) in fresh fracture populations.
      CONCLUSION: To support our findings direct comparative trials with safeguards
      against bias assessing outcomes important to patients, such as functional
      recovery, are required.

PMID- 24869617
TI  - Impact of perioperative acute ischemic stroke on the outcomes of noncardiac and
      nonvascular surgery: a single centre prospective study.
AB  - BACKGROUND: Although ischemic stroke is a well-known complication of
      cardiovascular surgery it has not been extensively studied in patients undergoing
      noncardiac surgery. The aim of this study was to assess the predictors and
      outcomes of perioperative acute ischemic stroke (PAIS) in patients undergoing
      noncardiothoracic, nonvascular surgery (NCS). METHODS: We prospectively evaluated
      patients undergoing NCS and enrolled patients older than 18 years who underwent
      an elective, non-daytime, open surgical procedure. Electrocardiography and
      cardiac biomarkers were obtained 1 day before surgery, and on postoperative days
      1, 3 and 7. RESULTS: Of the 1340 patients undergoing NCS, 31 (2.3%) experienced
      PAIS. Only age (odds ratio [OR] 2.5, 95% confidence interval [CI] 1.01-3.2, p <
      0.001) and preoperative history of stroke (OR 3.6, 95% CI 1.2-4.8, p < 0.001)
      were independent predictors of PAIS according to multivariate analysis. Patients
      with PAIS had more cardiovascular (51.6% v. 10.6%, p < 0.001) and
      noncardiovascular complications (67.7% v. 28.3%, p < 0.001). In-hospital
      mortality was 19.3% for the PAIS group and 1% for those without PAIS (p < 0.001).
      CONCLUSION: Age and preoperative history of stroke were strong risk factors for
      PAIS in patients undergoing NCS. Patients with PAIS carry an elevated risk of
      perioperative morbidity and mortality.

PMID- 24869618
TI  - The "weekend warrior": fact or fiction for major trauma?
AB  - BACKGROUND: The "weekend warrior" engages in demanding recreational sporting
      activities on weekends despite minimal physical activity during the week. We
      sought to identify the incidence and injury patterns of major trauma from
      recreational sporting activities on weekends versus weekdays. METHODS: We
      performed a retrospective cohort study using the Alberta Trauma Registry
      comparing all adults who were severely injured (injury severity score [ISS] >=
      12) while engaging in physical activity on weekends versus weekdays between 1995
      and 2009. RESULTS: Among the 351 identified patients (median ISS 18; median
      hospital stay 6 d; mortality 6.6%), significantly more were injured on the
      weekend than during the week (54.8% v. 45.2%, p = 0.016). Common mechanisms were
      motocross (23.6%), hiking or mountain/rock climbing (15.4%), skateboarding or
      rollerblading (12.3%), hockey/ice-skating (10.3%) and aircraft- (9.9%) and water
      related (7.7%) activities. This distribution was similar regardless of the day of
      the week. Most patients were injured as a result of a ground-level (21.9%) or
      higher fall while hiking, mountain climbing or rock climbing (25.9%); motocross
      related incidents (24.2%); or collision with a tree, person, man-made object or
      moving vehicle (14.0%). Injury patterns were similar across both groups (all p >
      0.05): head (55.8%), spine (35.1%), chest (35.0%), extremities (31.1%), face
      (17.4%), abdomen (13.1%). Surgical intervention was required in 41% of patients:
      15.1% required open reduction and internal fixation, 8.3% spinal fixation, 7.4%
      craniotomy, 5.1% facial repair and 4.3% laparotomy. CONCLUSION: The weekend
      warrior concept may be a validated entity for major trauma.

PMID- 24869619
TI  - Does regional variation impact decision-making in the management and palliation
      of pancreatic head adenocarcinoma? Results from an international survey.
AB  - BACKGROUND: Management and palliation of pancreatic head adenocarcinoma is
      challenging. End-of-life decision-making is a variable process involving multiple
      factors. METHODS: We conducted a qualitative, physician-based, 40-question
      international survey characterizing the impact of medical, religious, social,
      training and system factors on care. RESULTS: A total of 258 international
      clinicians completed the survey. Respondents were typically fellowship-trained
      (78%), with a mean of 16 years' experience in a university-affiliated (93%)
      hepato-pancreato-biliary group (96%) practice. Most (91%) believed resection is
      potentially curative. Most patients were discussed preoperatively by
      multidisciplinary teams (94%) and medical assessment clinics (68%), but rarely
      critical care (21%). Intraoperative surgical palliation included double bypass or
      no intervention for locally advanced nonresectable tumours (41% and 49% v. 14%
      and 85%, respectively, for patients with hepatic metastases). Postoperative
      admission to the intensive care unit was frequent (58%). Severe postoperative
      complications were often treated with aggressive cardiopulmonary resuscitation,
      intubation and critical care (96%), with no defined time points for futility
      (74%). Admitting surgeons guided most end-of-life decisions (97%). Formal medical
      futility laws were rarely available (26%). Insurance status did not alter
      treatment (97%) or palliation (95%) in non-universal care regions. Clinician
      experience, regional culture and training background impacted treatment (all p <
      0.05). CONCLUSION: Despite remarkable overall agreement, geographic and training
      differences are evident in the treatment and palliation of pancreatic head
      adenocarcinoma.

PMID- 24869620
TI  - Clinical outcomes of minimally invasive endoscopic and conventional sternotomy
      approaches for atrial septal defect repair.
AB  - BACKGROUND: Concerns remain that minimally invasive atrial septal defect (ASD)
      repair may compromise patient outcomes. We compared clinical outcomes of adult
      patients undergoing ASD repair via a minimally invasive endoscopic approach
      versus a "gold standard" sternotomy. METHODS: We retrospectively reviewed the
      clinical outcomes of consecutive patients who underwent ASD patch repair at our
      institution between 2002 and 2012. We compared in-hospital/30-day mortality,
      postoperative complications, length of stay in hospital and in the intensive care
      unit and blood product requirements between patients who underwent right mini
      thoracotomy (MT) and those who underwent conventional sternotomy. RESULTS: During
      the study period, 73 consecutive patients underwent ASD patch repair at our
      institution: 51 (age 47 +/- 16 yr, 66.7% women) in the MT group and 22 (age 46 +/
      21 yr, 59.1% women) in the sternotomy group. In-hospital mortality was similar
      between the 2 groups (MT 0% v. sternotomy 4.5%, p = 0.30). There were no
      significant differences in any postoperative complications or blood product
      requirements. No patients in the MT group suffered stroke, retrograde aortic
      dissection or leg ischemia. Mean intensive care unit (MT 1.2 +/- 1.2 d v.
      sternotomy 1.7 +/- 2.2 d, p = 0.26) and hospital length of stays (MT 5.1 +/- 2.2
      d v. sternotomy 6.3 +/- 3.6 d, p = 0.17) were similar between the groups;
      however, there was a trend toward fewer patients requiring prolonged hospital
      stays (> 10 d) in the MT group (3.9% v. 18.2%, p = 0.06). CONCLUSION: Repair of
      ostium secundum and sinus venosus ASD can be performed safely via MT endoscopic
      approach with similar outcomes as sternotomy. Patient preference for a more
      cosmetically appealing incision may be considered without concern of compromised
      outcomes.

PMID- 24869621
TI  - Attempting primary closure for all open fractures: the effectiveness of an
      institutional protocol.
AB  - BACKGROUND: Immediate primary closure of open fractures has been historically
      believed to increase the risk of wound infection and fracture nonunion. Recent
      literature has challenged this belief, but uncertainty remains as to whether
      primary closure can be used as routine practice. This study evaluates the impact
      of an institutional protocol mandating primary closure for all open fractures.
      METHODS: We retrospectively reviewed all open fractures treated in a single level
      1 trauma centre in a 5-year period. Prior to the study, a protocol was adopted
      standardizing management of open fractures and advocating primary closure of all
      wounds as a necessary goal of operative treatment. Patient and fracture
      characteristics, type of wound closure and development of infectious and bone
      healing complications were evaluated from time of injury to completion of
      outpatient follow-up. RESULTS: A total of 297 open fractures were treated, 255
      (85.8%) of them with immediate primary closure. Type III open injuries accounted
      for 24% of all injuries. Wounds that were immediately closed had a superficial
      infection rate of 11% and a deep infection rate of 4.7%. Both proportions are
      equivalent to or lower than historical controls for delayed closure. Fracture
      classification, velocity of trauma and time to wound closure did not correlate
      significantly with infection, delayed union or nonunion. CONCLUSION: Attempting
      primary closure for all open fractures is a safe and efficient practice that does
      not increase the postoperative risk of infection and delayed union or nonunion.

PMID- 24869622
TI  - Single-incision versus conventional laparoscopic appendectomy in 688 patients: a
      retrospective comparative analysis.
AB  - BACKGROUND: Laparoscopic surgery has become the standard for treating
      appendicitis. The cosmetic benefits of using single-incision laparoscopy are well
      known, but its duration, complications and time to recovery have not been well
      documented. We compared 2 laparoscopic approaches for treating appendicitis and
      evaluated postoperative pain, complications and time to full recovery. METHODS:
      We retrospectively reviewed the cases of consecutive patients with appendicitis
      and compared those who underwent conventional laparoscopic appendectomy (CLA)
      performed using 3 incisions and those who underwent single-incision laparoscopic
      appendectomy (SILA). During SILA, the single port was prepared to increase
      visibility of the operative site. RESULTS: Our analysis included 688 consecutive
      patients: 618 who underwent CLA and 70 who underwent SILA. Postsurgical
      complications occurred more frequently in the CLA than the SILA group (18.1% v.
      7.1%, p = 0.018). Patients who underwent SILA returned to oral feeding sooner
      than those who underwent CLA (median 12 h v. 22 h, p < 0.001). These between
      group differences remained significant after controlling for other factors.
      Direct comparison of only nonperforated cases, which was determined by
      pathological examination, revealed that SILA was significantly longer than CLA
      (60 min v. 50 min, p < 0.001). Patients who underwent SILA had longer in-hospital
      stays than those who underwent CLA (72 v. 55 h, p < 0.001); however, they had
      significantly fewer complications (3.0% v. 14.4%, p = 0.006). CONCLUSION: In
      addition to its cosmetic advantages, SILA led to rapid recovery and no increase
      in postsurgical pain or complications.

PMID- 24869624
TI  - Mimicking the 2-oxoglutaric acid signalling function using molecular probes:
      insights from structural and functional investigations.
AB  - 2-Oxoglutaric acid (2-OG) has gained considerable attention because of its newly
      discovered signalling role in addition to its established metabolic functions.
      With the aim of further exploring the signalling function of 2-OG, here we
      present a structure-activity relationship study using 2-OG probes bearing
      different carbon chain lengths and terminal groups. Our results highlight the
      importance of the five-membered carbon molecular skeleton and of the two
      carboxylic terminals in maintaining the signalling functions of the parent
      molecule 2-OG. These findings provide valuable information for designing new,
      effective molecular probes able to dissect and discriminate the newly discovered,
      complex signalling role of 2-OG from its canonical activity in metabolism. 

PMID- 24869623
TI  - A comparison of pain scores and medication use in patients undergoing single
      bundle or double-bundle anterior cruciate ligament reconstruction.
AB  - BACKGROUND: No gold standard exists for the management of postoperative pain
      following anterior cruciate ligament reconstruction (ACLR). We compared the pain
      scores and medication use of patients undergoing single-bundle (SB) or double
      bundle (DB) ACLR in the acute postoperative period. Pain and medication use was
      also analyzed for spinal versus general anesthesia approaches within both surgery
      types. METHODS: We assessed 2 separate cohorts of primary ACLR patients, SB and
      DB, for 14 days postoperatively. We used a standard logbook to record self
      reported pain scores and medication use. Pain was assessed using a 100 mm visual
      analogue scale (VAS). Medications were divided into 3 categories: oral opioids,
      oral nonsteroidal anti-inflammatories and acetaminophen. RESULTS: A total of 88
      patients undergoing SB and 41 undergoing DB ACLR were included in the study. We
      found no significant difference in VAS pain scores between the cohorts. Despite
      similar VAS pain scores, the DB cohort consumed significantly more opioid and
      analgesia medication (p = 0.011). Patients who underwent DB with spinal
      anesthesia experienced significantly less pain over the initial 14-day
      postoperative period than those who received general anesthesia (p < 0.001).
      CONCLUSION: Adequate pain relief was provided to all ACLR patients in the initial
      postoperative period. Patients in the DB cohort experienced more pain, as
      evidenced by the significant diffrence in consumption of opioids and
      acetaminophen, than the SB cohort. Patients who underwent spinal anesthesia
      experienced less pain in the acute postoperative period than those who received
      general anesthesia.

PMID- 24869626
TI  - A high efficiency CoCr2O4/carbon nanotubes nanocomposite electrocatalyst for dye
      sensitised solar cells.
AB  - A CoCr2O4/carbon nanotubes (CoCr2O4/CNTs) nanocomposite was successfully
      synthesised by a facile solution route, and used as an electrocatalyst for dye
      sensitised solar cells (DSSCs) for the first time, exhibiting a comparable power
      conversion efficiency of 8.40% to Pt-based DSSCs (eta = 8.68%) owing to the
      superior electrocatalytic activity of the nanocomposite. 

PMID- 24869627
TI  - Quantification of historical livestock importation into New Zealand 1860-1979.
AB  - AIMS: To quantify the numbers of live cattle, sheep and poultry imported into New
      Zealand and, where possible, their country of origin from 1860 to 1979. METHODS:
      Information on the origin and number of live animal importations into New Zealand
      was collected for cattle, sheep and poultry for the period 1868-1979 from the
      annual reports compiled by the New Zealand Registrar General's Office, Government
      Statistician's Office, Census and Statistics Office, Census and Statistics
      Department, Customs Department and Department of Statistics. Census data from
      1851 to 1871 were also used to estimate the livestock population during this
      period. The number of animals imported and the mean population for each species
      in a decade were determined, and the major countries of origin were identified.
      RESULTS: A large number of cattle (53,384) and sheep (604,525) were imported in
      the 1860s, and then there was a marked reduction in importations. Live poultry
      were imported in relatively small numbers (20,701) from 1880 to 1939, then
      1,564,330 live poultry were imported between 1960 and 1979. Australia was the
      predominant country of origin for sheep between 1868 and 1959 (51,347/60,918;
      84.3%) and of cattle between 1868 and 1979 (10,080/15,157; 66.5%). Only 6,712
      (11.0%) sheep and 3,909 (25.8%) cattle were imported from the United Kingdom over
      the same periods, and even fewer from other countries. CONCLUSIONS: The collated
      data and historical reports show that from 1860 to 1979 Australia has been the
      main source of livestock introduced into New Zealand. The pattern of importation
      showed that large numbers of cattle and sheep were initially imported in the
      1860s, probably in response to rapid agricultural expansion. Thereafter
      importations continued at much reduced numbers. In contrast, relatively small
      numbers of poultry were introduced until the 1960s when large numbers were
      imported as part of the development of a modern high-production industry. The
      overall pattern for both cattle and sheep was of a bottleneck event, as initially
      a relatively limited number of animals arrived from outside populations, followed
      by population expansion with ongoing but limited immigration (admixture).
      Investigation into the genetic population structure of New Zealand's cattle and
      sheep, as well as their host-associated microorganisms, could reflect the impact
      of these early historical events.

PMID- 24869629
TI  - Supercritical N2 processing as a route to the clean dehydrogenation of porous
      Mg(BH4)2.
AB  - Compounds of interest for chemical hydrogen storage at near ambient conditions
      are specifically tailored to be relatively unstable and thereby desorb H2 upon
      heating. Their decomposition must be performed in the absence of impurities to
      achieve clean dehydrogenation products, which is particularly challenging for an
      emerging class of microporous complex hydride materials, such as gamma-phase
      Mg(BH4)2, which exhibits high surface area and readily adsorbs (sometimes
      undesired) molecular species. We present a novel strategy toward the purification
      of gamma-Mg(BH4)2 using supercritical nitrogen drying techniques, (1) showing
      that clean hydrogen can be released from Mg(BH4)2 under mild conditions and (2)
      clarifying the origin of diborane among the decomposition products of stable
      borohydrides, a topic of critical importance for the reversibility and practical
      applicability of this class of hydrogen storage compounds. This technique is also
      widely applicable in the pursuit of the high-purity synthesis of other porous,
      reactive compounds, an exciting future class of advanced functional materials. 

PMID- 24869625
TI  - Impact of GeneXpert MTB/RIF on patients and tuberculosis programs in a low-burden
      setting. a hypothetical trial.
AB  - RATIONALE: Guidelines recommend routine nucleic-acid amplification testing in
      patients with presumed tuberculosis (TB), but these tests have not been widely
      adopted. GeneXpert MTB/RIF (Xpert), a novel, semiautomated TB nucleic-acid
      amplification test, has renewed interest in this technology, but data from low
      burden countries are limited. OBJECTIVES: We sought to estimate Xpert's potential
      clinical and public health impact on empiric treatment, contact investigation,
      and housing in patients undergoing TB evaluation. METHODS: We performed a
      prospective, cross-sectional study with 2-month follow-up comparing Xpert with
      standard strategies for evaluating outpatients for active pulmonary TB at the San
      Francisco Department of Public Health TB Clinic between May 2010 and June 2011.
      We calculated the diagnostic accuracy of standard algorithms for initial empiric
      TB treatment, contact investigation, and housing in reference to three
      Mycobacterium tuberculosis sputum cultures, as compared with that of a single
      sputum Xpert test. We estimated the incremental diagnostic value of Xpert, and
      the hypothetical reductions in unnecessary treatment, contact investigation, and
      housing if Xpert were adopted to guide management decisions. MEASUREMENTS AND
      MAIN RESULTS: A total of 156 patients underwent Xpert testing. Fifty-nine (38%)
      received empiric TB treatment. Thirteen (8%) had culture-positive TB. Xpert
      guided management would have hypothetically decreased overtreatment by 94%,
      eliminating a median of 44 overtreatment days (interquartile range, 43-47) per
      patient and 2,169 total overtreatment days (95% confidence interval, 1,938-2,400)
      annually, without reducing early detection of TB patients. We projected similar
      benefits for contact investigation and housing. CONCLUSIONS: Xpert could greatly
      reduce the frequency and impact of unnecessary empiric treatment, contact
      investigation, and housing, providing substantial patient and programmatic
      benefits if used in management decisions.

PMID- 24869630
TI  - Morphology controlled bulk synthesis of disc-shaped WO3 powder and evaluation of
      its photocatalytic activity for the degradation of phenols.
AB  - The surfactant assisted synthesis of disc-shaped WO3 powder and its
      photocatalytic performance in sunlight exposure is reported. UV-vis DRS, XRD and
      FESEM characterized the synthesized WO3. The synthesized powder exhibited a
      bandgap of ~2.55eV with cubic lattice and high crystallinity. The photocatalytic
      activity of the synthesized WO3 was examined for the degradation of phenol,
      resorcinol, 2-chlorophenol and 2-nitrophenol in complete spectrum and visible
      segment of sunlight. The highly efficient degradation/mineralization of 2-chloro
      and 2-nitrophenol compared to that of phenol and resorcinol, under identical
      experimental conditions, suggested the regulatory role of substituents attached
      to the aromatic ring in degradation/mineralization process. The time-scale HPLC
      degradation profiles, identification of intermediates by GC-MS and removal of
      organic carbon during the course of reaction were utilized to approximate the
      possible route of degradation/mineralization of phenolic substrates. The
      measurement of the anions released during the photocatalytic process was used to
      identify the nature of the major oxidants (O2(*-), OH(*)) and the possible
      interaction sites. A significant decrease in the photocatalytic activity of
      synthesized WO3, ~50%, was observed in visible portion of sunlight however, a
      sustained activity was observed in the repeated exposures. 

PMID- 24869632
TI  - Prodromal symptoms and early detection of Parkinson's disease in general
      practice: a nested case-control study.
AB  - BACKGROUND: Timely diagnosis of Parkinson's disease (PD), facilitating early
      intervention, depends largely on the GP's awareness of early symptomatology. For
      general practice, it is unknown which prodromal symptoms (symptoms preceding the
      typical motor symptoms of PD) demand the GP's alertness. OBJECTIVE: To assess
      prodromal symptoms that should alert the GP to the possibility of PD in primary
      care patients. METHODS: A nested case-control study was carried out in a
      population of approximately 12000 patients registered in the Continuous Morbidity
      Registration database affiliated with the University of Nijmegen in the
      Netherlands. The database pools subject data from four primary care practices.
      The subjects comprised all 86 patients diagnosed with PD between 1972 and 2007,
      and 78 controls, matched by sex, age, socioeconomic status and primary care
      practice. The primary measures of outcome were the prodromal symptoms presenting
      in the two years prior to the diagnosis of PD. The number (and type) of referrals
      and diagnostic tests were also assessed. RESULTS: In the two-year period prior to
      diagnosis, PD patients more often presented with functional somatic symptoms,
      constipation, hyperhidrosis and sleep disorders than controls. Patients also more
      frequently experienced more than one prodromal symptom and were more often
      referred within the primary care team or to a medical specialist. CONCLUSIONS:
      Prodromal symptoms of PD are encountered in general practice. GPs should be alert
      when patients present with multiple prodromal symptoms in a two-year period,
      especially considering the benefits of early intervention, and the future
      possibilities for disease-modifying therapy.

PMID- 24869631
TI  - Diagnostic value of FDG-PET/(CT) in children with fever of unknown origin and
      unexplained fever during immune suppression.
AB  - PURPOSE: Fever of unknown origin (FUO) and unexplained fever during immune
      suppression in children are challenging medical problems. The aim of this study
      is to investigate the diagnostic value of fluorine-18 fluorodeoxyglucose positron
      emission tomography (FDG-PET) and FDG-PET combined with computed tomography (FDG
      PET/CT) in children with FUO and in children with unexplained fever during immune
      suppression. METHODS: All FDG-PET/(CT) scans performed in the Radboud university
      medical center for the evaluation of FUO or unexplained fever during immune
      suppression in the last 10 years were reviewed. Results were compared with the
      final clinical diagnosis. RESULTS: FDG-PET/(CT) scans were performed in 31
      children with FUO. A final diagnosis was established in 16 cases (52 %). Of the
      total number of scans, 32 % were clinically helpful. The sensitivity and
      specificity of FDG-PET/CT in these patients was 80 % and 78 %, respectively. FDG
      PET/(CT) scans were performed in 12 children with unexplained fever during immune
      suppression. A final diagnosis was established in nine patients (75 %). Of the
      total number of these scans, 58 % were clinically helpful. The sensitivity and
      specificity of FDG-PET/CT in children with unexplained fever during immune
      suppression was 78 % and 67 %, respectively. CONCLUSIONS: FDG-PET/CT appears a
      valuable imaging technique in the evaluation of children with FUO and in the
      diagnostic process of children with unexplained fever during immune suppression.
      Prospective studies of FDG-PET/CT as part of a structured diagnostic protocol are
      warranted to assess the additional diagnostic value.

PMID- 24869633
TI  - Overexpression of the putative extracytoplasmic function sigma (sigma) factor
      FujE enhances FK506 production in Streptomyces sp. strain KCCM 11116P.
AB  - The role of the putative extracytoplasmic function sigma (sigma) factor FujE,
      which has not been characterized as a member of the FK506 biosynthetic gene
      cluster, on FK506 production was identified by gene deletion, overexpression, and
      transcription analysis experiments in Streptomyces sp. strain KCCM 11116P.
      Inactivation of fujE had no effect on FK506 production, growth, or morphological
      differentiation. Overexpression of fujE with integrative vectors increased FK506
      production by 2.87-fold (24.5 +/- 1.4 mg.L(-1)) compared with the wild type (8.5
      +/- 0.5 mg.L(-1)). Semiquantitative reverse transcription-polymerase chain
      reaction analysis indicated that the overexpression of fujE stimulates the
      transcription of the FK506 biosynthetic genes. These results demonstrated that
      fujE is a new member of the FK506 biosynthetic gene cluster.

PMID- 24869634
TI  - Identification of a bioactive Bowman-Birk inhibitor from an insect-resistant
      early maize inbred.
AB  - Breeding of maize, Zea mays, has improved insect resistance, but the genetic and
      biochemical basis of many of these improvements is unknown. Maize oligonucleotide
      microarrays were utilized to identify differentially expressed genes in leaves of
      three maize inbreds, parents Oh40B and W8 and progeny Oh43, developed in the
      1940s. Oh43 had enhanced leaf resistance to corn earworm larvae, Helicoverpa zea,
      and fall armyworm larvae, Spodoptera frugiperda, compared to one or both parents.
      Among ca. 100 significantly differentially expressed genes, expression of a
      Bowman-Birk trypsin inhibitor (BBI) gene was at least ca. 8-fold higher in Oh43
      than in either parent. The Oh43 BBI gene was expressed as a recombinant protein.
      Purified BBI inhibited trypsin and the growth of fall armyworm larvae when added
      to insect diet. These experiments indicate that comparative gene expression
      analysis combined with insect resistance measurements of early inbreds can
      identify previously unrecognized resistance genes. 

PMID- 24869635
TI  - Dissociation rates of H2 on a Ni(100) surface: the role of the physisorbed state.
AB  - The dissociation and recombination rates of physisorbed H2, and the total
      dissociation rate of gas phase H2 on the rigid Ni(100) surface, as well as the
      corresponding kinetic isotope effects, are calculated by using the quantum
      instanton method, together with path integral Monte Carlo and adaptive umbrella
      sampling techniques. Both the dissociation and recombination rates of physisorbed
      H2 are dramatically enhanced by the quantum motions of H2 at low temperatures,
      for instance, the quantum rates are 43 and 7.5 times larger than the classical
      ones at 200 K, respectively. For the dissociation of gas phase H2, at high
      temperatures, the H2 can fly over the physisorbed state and dissociate directly,
      however, at low temperatures, the H2 is first physisorbed and then dissociates
      under steady state approximation. The total dissociation rate of gas phase H2 can
      be expressed as a combination of the direct and steady state dissociation rates.
      It has the form of an inverted bell with a minimum value at about 400 K, and
      detailed analysis shows that the dissociation of gas phase H2 is dominated by a
      steady state process below 400 K, however, both the steady state and direct
      processes are important above 400 K. The calculated kinetic isotope effects
      reveal that H2 always has larger rates than D2 no matter which dissociative
      process they undergo. 

PMID- 24869636
TI  - p-MoO3 nanostructures/n-TiO2 nanofiber heterojunctions: controlled fabrication
      and enhanced photocatalytic properties.
AB  - In this work, p-MoO3 nanostructures/n-TiO2 nanofiber heterojunctions (p-MoO3/n
      TiO2-NF-HJs) were obtained by a two-step fabrication route. First, MoO2
      nanostructures were hydrothermally grown on electrospun TiO2 nanofibers. Second,
      by thermal treatment of the obtained MoO2 nanostructures/TiO2 nanofibers, p
      MoO3/n-TiO2-NF-HJs were obtained due to the phase transition of MoO2 to MoO3.
      With increasing the concentration of molybdenum precursor in hydrothermal
      process, the morphologies of MoO2 changed from nanoparticles to nanosheets, and
      then fully covered shells with an increased loading on TiO2 nanofibers. After
      calcination, the obtained p-MoO3/n-TiO2-NF-HJs possessed similar morphology to
      that without thermal treatment. X-ray photoelectron spectra showed that both Ti
      2p and OTi-O 1s peaks of p-MoO3/n-TiO2-NF-HJs shifted to higher binding energies
      than that of TiO2 nanofibers, suggesting electron transfer from TiO2 to MoO3 in
      the formation of p-n nanoheterojunctions. The p-n nanoheterojunctions decreased
      photoluminescence intensity, suppressed photogenerated electrons and holes
      recombinations, and enhanced charge separation and photocatalytic efficiencies.
      The apparent first-order rate constant for the degradation of RB by p-MoO3/n-TiO2
      NF-HJs with nanosheets surface morphology was two times that of TiO2 nanofibers.
      For the core/shell structure of p-MoO3/n-TiO2-NF-HJs, the internal electric field
      of p-n junction forced the photogenerated electrons transferring to TiO2 cores,
      then decreased the surface photocatalytic reactions and led to the lowest
      photocatalytic activity among the p-MoO3/n-TiO2-NF-HJs. 

PMID- 24869637
TI  - Effects of jacalin and follicle-stimulating hormone on in vitro goat primordial
      follicle activation, survival and gene expression.
AB  - This study aims to investigate the effects of jacalin and follicle-stimulating
      hormone (FSH) on activation and survival of goat primordial follicles, as well as
      on gene expression in cultured ovarian tissue. Ovarian fragments were cultured
      for 6 days in minimum essential medium (MEM) supplemented with jacalin (10, 25,
      50 or 100 MUg/ml - Experiment 1) or in MEM supplemented with jacalin (50 MUg/ml),
      FSH (50 ng/ml) or both (Experiment 2). Non-cultured and cultured tissues were
      processed for histological and ultrastructural analysis. Cultured tissues from
      Experiment 2 were also stored to evaluate the expression of BMP-15, KL (Kit
      ligand), c-kit, GDF-9 and proliferating cell nuclear antigen (PCNA) by real-time
      polymerase chain reaction (PCR). The results of Experiment 1 showed that,
      compared with tissue that was cultured in control medium, the presence of 50
      MUg/ml of jacalin increased both the percentages of developing follicles and
      viability. In Experiment 2, after 6 days, higher percentages of normal follicles
      were observed in tissue cultured in presence of FSH, jacalin or both, but no
      synergistic interaction between FSH and jacalin was observed. These substances
      had no significant effect on the levels of mRNA for BMP-15 and KL, but FSH
      increased significantly the levels of mRNA for PCNA and c-kit. On the other hand,
      jacalin reduced the levels of mRNA for GDF-9. In conclusion, jacalin and FSH are
      able to improve primordial follicle activation and survival after 6 days of
      culture. Furthermore, presence of FSH increases the expression of mRNA for PCNA
      and c-kit, but jacalin resulted in lower GDF-9 mRNA expression. 

PMID- 24869638
TI  - Emission of isothiazolinones from water-based paints.
AB  - The isothiazolinone preservatives methylisothiazolinone (MI),
      methylchloroisothiazolinone (MCI), and benzisothiazolinone (BIT) are used in a
      wide variety of products including paint and cosmetics, and they are known to
      cause allergic contact dermatitis. Among painters they are one of the most common
      causes of contact dermatitis. Furthermore, they are all volatile, and severe
      reactions caused by emissions of especially MI from paint have been reported
      recently. In this study the concentrations of MI, BIT, and MCI in water-based
      paint were analyzed by LC-MS-MS, and the emissions from the paints were measured
      in climate chambers and in an apartment. Nineteen paints were analyzed for the
      content of MI, MCI, and BIT. All 19 paints contained MI, 16 contained BIT, and 4
      contained MCI. In the chamber experiment emission of MI peaked within hours of
      application but then continued at a slow rate for more than 42 days. MCI was
      emitted more slowly and peaked after several days. BIT emissions were all around
      the limit of detection. In the apartment we were able to detect emission of MI
      several days after application. Long lasting evaporation and thus chronic
      exposure give credibility to the clinical observations that MI can be an
      important cause of airborne contact dermatitis among painters and consumers. 

PMID- 24869641
TI  - Canine sperm cryopreservation using glucose in glycerol-free Tris.
AB  - OBJECTIVE: The study is to develop a glycerol-free extender using glucose for
      canine sperm cryopreservation,. METHODS: Tris [hydroxymethyl] aminomethane (TRIS)
      extender. Canine sperm were cooled to 4 degree C in TRIS containing 44.4 mM
      glucose for 100 min, and then cooled at 4 degree C in TRIS with glucose
      concentrations of 0 mM, 44.4 mM, 100 mM, 200 mM, or 300 mM for 30 min followed by
      cryopreservation. After thawing at 37 degree C for 25 sec, sperm motility,
      viability, and morphological abnormalities were evaluated. In addition, 300 mM
      glucose-TRIS was compared to TRIS extenders with a final concentration of 5 %
      glycerol. Sperm phosphatidylserine (PS) translocation after freezing and thawing
      was assayed by flow cytometry using Annexin V-FITC apoptosis detection kit.
      RESULTS: Progressive motility and viability (42% and 41%, respectively) were
      significantly higher in the 300mM group than the other groups with lower
      concentrations of glucose (P < 0.05). PS translocation index was significantly
      lower in 300mM glucose-TRIS than those in extenders with glycerol (85 vs 93, P <
      0.05). CONCLUSION: These results indicate that cryopreservation of canine sperm
      using glycerol-free 300 mM glucose-TRIS is feasible and yields more motile sperm
      with lower PS translocation compared with extenders containing glycerol.

PMID- 24869642
TI  - Development of a method of vitrification, thawing, and transfer of mammalian
      blastocysts using a single closed cryo-straw.
AB  - BACKGROUND: There are different methods for cryopreservation of mammalian embryos
      with variable degrees of success. These methods require specific vessels for
      embryo vitrification, thawing, and transfer. OBJECTIVE: Here, we report a simple
      and inexpensive way to vitrify, thaw and transfer mammalian blastocysts in one
      straw. METHODS: This in-straw vitrification solution with microdrop (ISVDM) was
      compared with EM grid and normal 0.25 mL straw methods. RESULTS: There were no
      differences in the rates of re-expanded and hatching-to-hatched murine and bovine
      blastocysts exposed to 1, 0.5, and 0.3 M of sucrose in the diluent that was
      loaded into the straw. Low re-expanded and hatching-to-hatched rates of murine
      and bovine blastocysts were observed with PBS only. The pregnancy rates of
      control murine blastocysts (57.1%) and blastocysts exposed to 0.3 M sucrose in
      diluent and ISVDM (71.4%) were significantly higher (p < 0.05) than those exposed
      to 1, 0.5, and 0 M sucrose and those loaded into 0.25 mL straws. The rate of
      offspring delivery was highest in the control group. There was no significant
      difference (p < 0.05) in the rate of offspring delivery among ISVDM, 0.25 mL
      straw, and EM grid groups. CONCLUSION: Our results indicate that vitrified
      embryos can be warmed and diluted in a single straw and that this one-step method
      enables farm animal embryo transfer without a microscope or other laboratory
      equipment.

PMID- 24869644
TI  - Cryopreservation of Thymus lotocephalus shoot tips and assessment of genetic
      stability.
AB  - BACKGROUND: Thymus lotocephalus is a rare endemic species from the Algarve,
      Portugal, and is legally protected by Portuguese and European legislation.
      OBJECTIVE: The aim is to develop a cryopreservation protocol for T. lotocephalus
      shoot tips, as an alternative approach for the long-term conservation of this
      species. METHODS: Several methods (droplet-vitrification, vitrification and
      encapsulation-dehydration) were tested. Conditions regarding the subculture
      period, cold-hardening and preculture were optimized. Cryopreserved shoot tips
      were also assessed for their genetic stability using RAPD markers. RESULTS:
      Droplet-vitrification presented the best results. The best regrowth of
      cryopreserved shoot tips obtained eight weeks after rewarming was 67%. This was
      accomplished with four weeks subculture period of in vitro-donor plants at 25
      degree C, preculture of excised shoot tips for one day on MS medium containing
      0.3 M sucrose, treatment in PVS2 for 60 min, and MS supplemented with 0.2 mg per
      L zeatin as recovery medium. The assessment using RAPD markers observed variation
      at a low frequency and shoots regenerated from cryopreserved apices showed normal
      development compared to the regular in vitro-grown shoots. CONCLUSION: Droplet
      vitrification is thus a viable method for the cryopreservation of T. lotocephalus
      shoot tips.

PMID- 24869643
TI  - Freeze-thawing induced structural and functional changes in glucose oxidase.
AB  - BACKGROUND: Glucose oxidase enzyme may be a suitable model for studying the
      effect of low temperatures on structural and functional properties of
      biomacromolecules. OBJECTIVE: The research aim was to study the freeze-thawing
      effect on glucose oxidase isolated and immobilized by cross-linking with
      glutaraldehyde METHODS: Effects of freezing rates on conformation and activity of
      glucose oxidase isolated and cross-linked in solution with gluteraldehyde was
      studied. RESULTS: Freezing with slow rate (2 degree C per min) induces
      significant protein aggregation, activity reduction and conformational changes in
      polar and hydrophobic regions. Freezing at 100 degree C per min, however, causes
      conformational changes primarily in polar regions, insignificant aggregation,
      depending on the number of freeze-thawing cycles and increases enzyme activity.
      CONCLUSION: With the rise in glucose oxidase concentration in solution the low
      temperature-induced destabilization effect is reduced both during low and rapid
      freezing. At the slow cooling rate, cross-linking with glutaraldehyde results in
      more conformation alterations in polar regions of proteins, accompanied with an
      increase in enzyme activity.

PMID- 24869645
TI  - Cryopreservation of protocorm-like body-derived shoot tips of Calanthe davidii by
      droplet-vitrification.
AB  - BACKGROUND: Evaluation of the conservation status of Calanthe plants in China
      indicated that 18 species were endangered or critically endangered. Comprehensive
      conservation solutions including ex situ methods, are urgently required to
      protect Calanthe species in China. OBJECTIVE: The study aims to develop a simple
      and efficient cryopreservation protocol using droplet-vitrification for Calanthe
      davidii. METHODS: Protocorm-like bodies (PLBs) were induced from nodal sections
      of in vitro shoots, and their proliferation was promoted by a thin cell layer
      culture procedure. Shoot tips excised from three leaf-stage PLBs were used in
      cryopreservation experiments. Key factors of the droplet-vitrification procedure
      including sucrose preculture, treatment with PVS2 solution and post-rewarming
      culture conditions were optimized to achieve a high level of regeneration.
      RESULTS: When the optimized procedure was applied, 77.8 +/- 3.9% of cryopreserved
      shoot tips withstood liquid nitrogen exposure and regenerated into new PLBs.
      CONCLUSION: These results highlighted the importance of post-rewarming osmo
      conditioning for regeneration of cryopreserved shoot tips.

PMID- 24869646
TI  - Development of vitrification protocol in Rubia akane (nakai) hairy roots using a
      systematic approach.
AB  - BACKGROUND: A solution-based vitrification protocol is a process of sequentially
      changing-solutions from which both influx of cryoprotectants (loading) and efflux
      of water (dehydration) were accomplished before cryo-exposure. Hence, we need to
      properly control the concentration /composition of the cryoprotectant solutions.
      OBJECTIVE: The study was, using a systematic approach, to develop a protocol for
      Rubia akane hairy roots, a very sensitive material to cytotoxicity of
      vitrification solutions. METHODS: Due to the poor response of 10-year in vitro
      maintained R. akane hairy roots to already established cryopreservation
      protocols, the following sets of experiments were designed: 1) combinational
      effect of preculture, osmoprotection and cryoprotection with PVS2-based (A3-70%)
      and PVS3-based (B5-80%) vitrification solutions; 2) different cooling/warming
      rates and warming temperature; 3) varying unloading solutions (25%, 35%and 45%
      sucrose) and durations (7 min and 30 min) with or without changing the unloading
      solutions. RESULTS: Preculture and osmoprotection treatments were necessary to
      acquire cytotoxicity tolerance in both vitrification solutions tested and
      osmoprotection treatment was more critical, especially in B5-80%. A sequential
      osmoprotection treatment (C10-50%) following conventional osmoprotection (C4-35%)
      was needed to increase the post-cryopreservation regrowth. Aluminum foil strips
      were superior to cryovials, but the warming temperature tested (20 degree C and
      40 degree C) did not affect post-cryopreservation recovery. In the unloading
      procedure, a longer duration (30 min) with a higher sucrose solution (S-45%) was
      harmful, possibly due to osmotic stress. CONCLUSION: R. akane hairy roots are
      very sensitive to cytotoxicity (both osmotic stress and chemical toxicity) and
      thus a proper process (preculture, osmoprotection, cryoprotection and unloading)
      is necessary for higher post-cryopreservation recovery.

PMID- 24869648
TI  - Pre and post lipocryolysis thermic conditioning enhances rat adipocyte
      destruction.
AB  - BACKGROUND: New knowledge about crystallization vs. lipid-to-gel transition has
      surfaced recently, since some of the latest publications on lipocryolysis have
      focused on its action mechanism. As a result, new opportunities for technical
      improvements and clinical outcome optimization have opened up. The food industry
      has been working with lipid crystal polymorphisms for decades, and tempering
      seems to be the easiest method of external conditioning, in addition to being
      harmless. OBJECTIVE: Evaluate if pre and post lipocryolyisis thermic conditioning
      enhances rat adipocyte destruction. METHODS: Several temperature treatment
      patterns (TTP) were applied to isolated rat adipocytes. The survival of the
      adipocytes exposed to the different TTPs and the formation of crystals in the
      surviving adipocytes were assessed and analyzed. RESULT: Pre and post
      lipocryolysis thermic conditioning changed lipocryolyisis crystallization process
      and showed an enhancement in adipocyte destruction that could represent an
      important step in improving clinical results. CONCLUSIONS: pre and post
      lipocryolyisis thermic conditioning enhances rat adipocyte destruction.

PMID- 24869647
TI  - IVF recovery of mutant mouse lines using sperm cryopreserved with mtg in
      cryovials.
AB  - BACKGROUND: Modification of cryoprotective medium (CPM) R18S3 (18% raffinose and
      3% skim milk) by addition of monothioglycerol (MTG) or L-glutamine (Glu) has been
      shown to improve in vitro fertilization (IVF) using mouse sperm cryopreserved in
      cryostraws. However, whether these CPMs can be applied effectively to sperm
      cryopreserved in cryovials is unknown. OBJECTIVE: The study was to determine the
      comparative effectiveness of using R18S3, R18S3+Glu (100mM and 87 mM), or
      R18S3+MTG (477 uM) to cryopreserve various sample volumes of mouse sperm in
      cryovials and cryostraws. METHODS: This study compared the effects of different
      CPMs on motility of fresh and frozen-thawed C57BL/6J sperm and on IVF rate of
      C57BL/6J sperm cryopreserved in different CPMs and containers with different
      volumes, and then used technologies developed to cryopreserve and recover sperm
      of knockout mouse lines on inbred C57BL/6 backgrounds. RESULTS: Glutamine at 100
      mM inhibited, but MTG at 477 uM protected, fresh sperm motility significantly (P
      < 0.05). Sperm cryopreserved in R18S3+MTG had significantly better (P < 0.05)
      post-thaw progressive motility and IVF rate than when cryopreserved in R18S3
      alone, R18S3+Glu (100 mM), or RSGlu87 (15.7% raffinose, 2.6% skim milk, and 87 mM
      L-glutamine). There was no significant difference in IVF rates among sperm
      cryopreserved with R18S3+MTG in cryovials or in cryostraws (P > 0.05). Sperm from
      63 knockout mouse lines on C57BL/6 backgrounds cryopreserved using R18S3+MTG in
      cryovials were all recovered successfully to genotypically-confirmed offspring.
      CONCLUSION: Mouse sperm on C56BL/6 backgrounds can be successfully cryopreserved
      in cryovials using R18S3+MTG.

PMID- 24869649
TI  - Cryopreservation of native Kazakhstan apricot (Prunus armeniaca l) seeds and
      embryonic axes.
AB  - BACKGROUND: Preserving the genetic diversity of Central Asia includes conserving
      wild apricots found in the foothills of several mountain ranges. These include
      primitive and genetically diverse populations with important characteristics for
      crop improvement. Apricot seeds have a short storage life, so cryopreservation of
      the seeds of wild populations is important for conserving the genetic diversity.
      OBJECTIVE: This study was to determine a suitable protocol for long-term storage.
      METHODS: This study tested a range of protocols using embryos and embryonic axes
      for storage of an important population of wild apricots and to determine if seed
      size and the distribution of moisture in the seed play a role in successful
      cryopreservation. RESULTS: Germination of scarified whole seed from trees in the
      Jungar population of Prunus armeniaca varied from 63 to 90 percent after 1 h in
      liquid nitrogen (LN) and was generally better at 7 % moisture content (MC) than
      at the original 14 percent MC. Embryos (4 percent MC) from stratified seed had
      only 33 % germination after LN exposure. Isolated embryonic axes from non
      stratified seed germinated at 86 to 100 % following drying to 4 % or 7 % MC.
      Examination of three seed sizes determined that the MC of whole seed, embryos and
      isolated axes varied with the seed size and shape. MC of whole seeds and embryos
      decreased as size decreased, however, the axis MC did not. MC of medium-size seed
      was more evenly distributed between the axis and endosperm than in the larger or
      smaller samples. Cryopreservation of axes from medium-sized seed was good at any
      moisture content and a 1-h drying time was significantly better than 90 min. for
      axes of all seed sizes. Cryopreservation of axes using vitrification protocols
      initially designed for shoot tips produced germination similar to or lower than
      seed and axis drying techniques. CONCLUSION: We recommend storing apricot
      germplasm as unstratified seed dried to 7 % MC or as isolated embryonic axes.

PMID- 24869650
TI  - Vitrification of equine oocytes with a polyvinyl alcohol after in vitro
      maturation with equine growth hormone and insulin-like growth factor-I.
AB  - BACKGROUND: In vitro fertilization (IVF) procedures are limited by the inability
      to mature equine oocytes on in vitro methods. OBJECTIVE: The aim of this study
      was to evaluate structural integrity of equine oocytes subjected to vitrification
      with a synthetic polymer (PVA). METHODS: The effect of eGH and its relationship
      with IGF-I on in vitro maturation (IVM) were evaluated. Compact cumulus oocytes
      complexes (n=122) were cultured in TCM-199 with eGH, IGF-I or eGH+IGF-I for 30h
      at 38.5C in air with 5 % CO2. Oocytes were fixed after IVM or subjected to the
      vitrification protocol. Cryopreserved oocytes were exposed to 1.4M DMSO+1.8M EG+1
      percent PVA for 3min, and then transfer to 2.8M DMSO+3.6M EG+0.6M sucrose+1 % PVA
      for 1min. After rewarming, oocytes were evaluated by confocal microscopy.
      RESULTS: Maturation rates of oocytes were not significant different among groups
      (P > 0.05), however eGH+IGF-I group can develop the assessment of resumption of
      meiosis (MI+MII = 86.7 %). CONCLUSION: The oocyte did not show morphological
      alterations. The use of PVA-copolymer may represent a potential alternative for
      vitrification of equine oocytes after IVM.

PMID- 24869652
TI  - Widespread ulcerated and vegetative plaques with an unusual rhinophymatous nose.

PMID- 24869651
TI  - Effect of vascular network and nanoparticles on heat transfer and intracellular
      ice formation in tumor tissues during cryosurgery.
AB  - BACKGROUND: Cryosurgery is a physical therapy of tumor treatment which is welcome
      in clinics for its minimally invasive advantage. However, the high recurrence
      rate makes the conventional cryosurgery unsatisfactory, which needs adjuvant
      treatment such as introduction of nanoparticles. OBJECTIVE: This study is to
      examine the effects of vascular network and MgO nanoparticles on heat transfer
      and intracellular ice formation in tumor tissues during cryosurgery. METHOD: We
      developed a multi-scale model to study the efficiency of cryosurgery, including
      the macro-level (mass tumor tissue) heat transfer and the micro-level (tumor
      cells) probability of intracellular ice formation (PIF). The model is used to
      examine the effects of fractal vascular network (VN) and nanoparticles with
      different concentration on heat transfer and PIF during cryosurgery in the breast
      cancer tissue (MCF-7 cells). The nucleation rate kinetic parameter and the
      thermodynamic parameter of MCF-7 cells are determined by nonlinear curve-fitting
      the published experimental data, and then the probability of intracellular ice
      formation of the picked points in the tumor tissue are determined using the
      classic model for intracellular ice nucleation with the simulated thermal
      profiles at those points during cryosurgery. RESULTS AND CONCLUSION: The
      introduction of nanoparticles have significantly enhanced the heat transfer in
      the mass tumor tissue and increased the PIF of tumor cells, indicating the
      nanocryosurgery is more efficient than conventional cryosurgery.

PMID- 24869653
TI  - Anion receptors based on highly fluorinated aromatic scaffolds.
AB  - Mono-, di-, and tri-pentafluorobenzyl-substituted hexafluorobenzene (HFB)
      scaffolds, viz., R(I), R(II), and R(III) are proposed as promising receptors for
      molecules of chemical, biological, and environmental relevance, viz., N2, O3,
      H2O, H2O2, F(-), Cl(-), BF4(-), NO3(-), ClO(-), ClO2(-), ClO3(-), ClO4(-), and
      SO4(2-). The receptor-guest complexes modeled using M06L/6-311++G(d,p) DFT show a
      remarkable increase in the complexation energy (E(int)) with an increase in the
      number of fluorinated aromatic moieties in the receptor. Electron density
      analysis shows that fluorinated aromatic moieties facilitate the formation of
      large number of lone pair-pi interactions around the guest molecule. The lone
      pair strength of the guest molecules quantified in terms of the absolute minimum
      (V(min)) of molecular electrostatic potential show that E(int) strongly depends
      on the electron deficient nature of the receptor as well as strength of lone
      pairs in the guest molecule. Compared to HFB, R(I) exhibits 1.1-2.5-fold, R(II)
      shows 1.6-3.6-fold, and the bowl-shaped R(III) gives 1.8-4.7-fold increase in the
      magnitude of E(int). For instance, in the cases of HFB...F(-), R(I)...F(-),
      R(II)...F(-), and R(III)...F(-) the E(int) values are -21.1, -33.7, -38.1, and 
      50.5 kcal/mol, respectively. The results strongly suggest that tuning lone pair
      pi interaction provides a powerful strategy to design receptors for small
      molecules and anions.

PMID- 24869654
TI  - Rhodium-catalyzed regio- and stereoselective oxyamination of dienes via tandem
      aziridination/ring-opening of dienyl carbamates.
AB  - The reaction of dienyl carbamates with PhI(OR)2 in the presence of rhodium
      catalysts affords vinyl aziridines which are in situ regio- and stereoselectively
      opened to afford oxyamination products resulting from a selective S(N)2
      (Rh2(OAc)4/PhI(OPiv)2) or S(N)2' (Rh2(OPiv)4/PhI(OAc)2) opening. The scope and
      limitations of this tandem process are described.

PMID- 24869658
TI  - Protein kinase inhibitor beta enhances the constitutive activity of G-protein
      coupled zinc receptor GPR39.
AB  - GPR39 is a G-protein-coupled zinc receptor that protects against diverse
      effectors of cell death. Its protective activity is mediated via constitutive
      activation of Galpha13 and the RhoA pathway, leading to increased SRE (serum
      response element)-dependent transcription; the zinc-dependent immediate
      activation of GPR39 involves Gq-mediated increases in cytosolic Ca2+ and Gs
      coupling leading to increased cAMP levels. We used the cytosolic and soluble C
      terminus of GPR39 in a Y2H (yeast-2-hybrid) screen for interacting proteins, thus
      identifying PKIB (protein kinase A inhibitor beta). Co-expression of GPR39 with
      PKIB increased the protective activity of GPR39 via the constitutive, but not the
      ligand-mediated, pathway. PKIB inhibits protein kinase A by direct interaction
      with its pseudosubstrate domain; mutation of this domain abolished the inhibitory
      activity of PKIB on protein kinase A activity, but had no effect on the
      interaction with GPR39, cell protection and induction of SRE-dependent
      transcription. Zinc caused dissociation of PKIB from GPR39, thereby liberating it
      to associate with protein kinase A and inhibit its activity, which would result
      in a negative-feedback loop with the ability to limit activation of the Gs
      pathway by zinc. 

PMID- 24869660
TI  - Sequential direct SNAr reactions of pentafluorobenzenes with azole or indole
      derivatives.
AB  - Sequential regioselective N-arylations through high-yielding catalyst-free direct
      SNAr reactions of pentafluorobenzene derivatives with azole or indole derivatives
      are described. The N-arylated derivatives were further functionalized through a
      microwave-assisted cross-coupling reaction via C-H bond activation or Suzuki
      conditions. The order of the reactions could be reversed, proving full
      orthogonality between the reactions which led to well-defined fully substituted
      benzene derivatives. 

PMID- 24869662
TI  - Real-time fluorescence visualization of slow tautomerization of single free-base
      phthalocyanines under ambient conditions.
AB  - The emission transition dipole moments of single-molecule free-base
      phthalocyanines at an air/glass interface were visualized using defocused wide
      field fluorescence microscopy at a temporal resolution of 100-200 ms. Isolated
      molecules showed slow proton tautomerization, which is consistent with previous
      theoretical calculations in the gas phase, which predicted large activation
      energies. 

PMID- 24869661
TI  - Identification and expression analysis of a doublesex1 gene in Daphnia pulex
      during different reproductive stages.
AB  - The gene doublesex (dsx) has shown deep conservation in the sex determination in
      many organisms. Environmental stimuli initiate a switch in the reproductive
      strategy of Daphnia pulex from asexual to sexual reproduction; however,
      occasionally, changes in environmental conditions will not lead to this
      transition. So study genetic responses to environmental stimuli and the molecular
      basis for the switch of reproductive stages are urgently needed. Therefore, we
      isolated and sequenced a D. pulex doublesex1 gene (Dpdsx1) and analyzed its
      expression and location by quantitative polymerase chain reaction (qPCR) and
      whole-mount in situ hybridization in D. pulex during different stages of
      reproduction. The predicted amino acid sequence has 335 amino acids that
      contained one DM domain and one dimerization domain, which is characteristic of
      insect orthologs of Dsx. Real-time PCR showed that Dpdsx1 expression decreased
      significantly (P < 0.05) in different reproductive stages in the following order:
      male, parthenogenetic female, ephippial female, resting egg, and juvenile female.
      Whole-mount in situ hybridization revealed that Dpdsx1 is expressed in the first
      antennae, first thoracic limb and compound eye in males, whereas expression
      levels in the corresponding sites of parthenogenetic and ephippial females were
      relatively weak. Dpdsx1 could not be detected in the gonads of males or ephippial
      and parthenogenetic females. Taken together, these different reproductive stages'
      and sex specific expression patterns are regulated temporally and spatially. We
      speculate that Dpdsx1 may involve in switching different stages of reproduction
      and in sexual differentiation in D. pulex.

PMID- 24869663
TI  - In vitro design of a novel lytic bacteriophage cocktail with therapeutic
      potential against organisms causing diabetic foot infections.
AB  - In patients with diabetes mellitus, foot infections pose a significant risk.
      These are complex infections commonly caused by Staphylococcus aureus,
      Pseudomonas aeruginosa and Acinetobacter baumannii, all of which are potentially
      susceptible to bacteriophages. Here, we characterized five bacteriophages that we
      had determined previously to have antimicrobial and wound-healing potential in
      chronic S. aureus, P. aeruginosa and A. baumannii infections. Morphological and
      genetic features indicated that the bacteriophages were lytic members of the
      family Myoviridae or Podoviridae and did not harbour any known bacterial
      virulence genes. Combinations of the bacteriophages had broad host ranges for the
      different target bacterial species. The activity of the bacteriophages against
      planktonic cells revealed effective, early killing at 4 h, followed by bacterial
      regrowth to pre-treatment levels by 24 h. Using metabolic activity as a measure
      of cell viability within established biofilms, we found significant cell
      impairment following bacteriophage exposure. Repeated treatment every 4 h caused
      a further decrease in cell activity. The greatest effects on both planktonic and
      biofilm cells occurred at a bacteriophage : bacterium input multiplicity of 10.
      These studies on both planktonic cells and established biofilms allowed us to
      better evaluate the effects of a high input multiplicity and a multiple-dose
      treatment protocol, and the findings support further clinical development of
      bacteriophage therapy. 

PMID- 24869670
TI  - FcgammaRIIB regulates T-cell autoreactivity, ANCA production, and neutrophil
      activation to suppress anti-myeloperoxidase glomerulonephritis.
AB  - Anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis
      involves innate and adaptive immune cells in the induction of autoimmunity and in
      autoimmune effector responses. Most Fcgamma receptors (FcgammaRs) activate immune
      cells, but FcgammaRIIB, found in humans and mice on B cells and innate cells, is
      an inhibitory receptor. Here we tested whether endogenous FcgammaRIIB negatively
      regulates autoreactivity and effector responses in experimental anti
      myeloperoxidase (MPO) glomerulonephritis, using wild-type and FcgammaRIIB(-/-)
      mice. After MPO immunization, FcgammaRIIB(-/-) mice developed higher MPO-ANCA
      titers and increased anti-MPO T-cell responses. Transfer of FcgammaRIIB-deficient
      dendritic cells loaded with a nephritogenic MPO peptide (MPO409-428) into wild
      type mice induced stronger autoimmunity than dendritic cells derived from wild
      type mice. Transferring anti-MPO antibodies into lipopolysaccharide-primed mice
      resulted in increased glomerular neutrophil accumulation and injury in
      FcgammaRIIB(-/-) mice, showing a role for FcgammaRIIB in suppressing neutrophil
      activation. Inducing active autoimmunity to MPO followed by triggering T cell
      mediated glomerular injury by transfer of sub-nephritogenic doses of
      lipopolysaccharide and anti-MPO antibodies resulted in more disease in
      FcgammaRIIB(-/-) mice. Thus, endogenous FcgammaRIIB negatively regulates anti-MPO
      autoimmunity and glomerulonephritis by dendritic cells, B cells, and neutrophils
      to limit MPO-ANCA production, T-cell responses, and neutrophil activation. 

PMID- 24869669
TI  - Impact of platelet transfusion on survival of patients with intracerebral
      hemorrhage after administration of anti-platelet agents at a tertiary emergency
      center.
AB  - This study examined the impact of platelet transfusion (PLT) on the survival of
      intracerebral hemorrhage (ICH) patients who had been administered anti-platelet
      agents (APA). This retrospective cohort analysis investigated 432 patients (259
      men, 60%) who were newly diagnosed with ICH between January 2006 and June 2011 at
      the tertiary emergency center of Kitasato University Hospital. Median age on
      arrival was 67.0 years (range, 40-95 years). ICH was subcortical in 72 patients
      (16.7%), supratentorial in 233 (53.9%), and infratentorial in 133 (30.8%). PLT
      was performed in 16 patients (3.7%). Within 90 days after admission to the
      center, 178 patients (41.2%) had died due to ICH. Before the onset of ICH, 66
      patients had been prescribed APA because of atherosclerotic diseases.
      Multivariate regression analysis indicated APA administration was an independent
      risk factor for death within 7 days (odds ratio, 5.12; P = 0.006) and within 90
      days (hazard ratio, 1.87; P = 0.006) after arrival. Regarding the effect of a PLT
      in ICH patients with APA, no patient with PLT died. PLT had a survival benefit on
      patients with ICH, according to our analysis. Further prospective analysis is
      necessary to confirm the effects of PLT on survival in ICH with APA. 

PMID- 24869671
TI  - The clinical significance of medial arterial calcification in end-stage renal
      disease in women.
AB  - Medial arterial calcification is common in advanced kidney disease but its impact
      on cardiovascular disease is uncertain because imaging techniques used to date
      cannot reliably distinguish it from atherosclerotic calcification. We have
      previously shown that breast arterial calcification (BAC) is exclusively medial
      and is a marker of generalized medial calcification in end-stage renal disease
      (ESRD). Therefore, the presence of BAC on mammograms in 202 women with ESRD (mean
      duration 4.1 years) was correlated with cardiovascular events to determine the
      clinical significance of medial arterial calcification. BAC was found in 58% of
      the study participants and was significantly associated with age, diabetes, and
      ESRD duration. Both coronary artery (27 vs. 15%) and peripheral arterial disease
      (PAD; 19 vs. 4%) were more likely in patients with BAC but only the latter
      persisted after accounting for other factors (odds ratio 4.6; 95% confidence
      interval 1.2-15). In 142 women without clinical events before mammography, BAC
      was associated with a greater incidence of new PAD events (13 vs. 3%) but not
      coronary artery disease events (11 vs. 11%). Thus, BAC is strongly and
      independently associated with PAD in women with ESRD and may be predictive of
      clinical events. This suggests that medial arterial calcification is a clinically
      significant lesion that may contribute to the accelerated PAD in ESRD. 

PMID- 24869675
TI  - Deep data analysis of conductive phenomena on complex oxide interfaces: physics
      from data mining.
AB  - Spatial variability of electronic transport in BiFeO3-CoFe2O4 (BFO-CFO) self
      assembled heterostructures is explored using spatially resolved first-order
      reversal curve (FORC) current voltage (IV) mapping. Multivariate statistical
      analysis of FORC-IV data classifies statistically significant behaviors and maps
      characteristic responses spatially. In particular, regions of grain, matrix, and
      grain boundary responses are clearly identified. k-Means and Bayesian demixing
      analysis suggest the characteristic response be separated into four components,
      with hysteretic-type behavior localized at the BFO-CFO tubular interfaces. The
      conditions under which Bayesian components allow direct physical interpretation
      are explored, and transport mechanisms at the grain boundaries and individual
      phases are analyzed. This approach conjoins multivariate statistical analysis
      with physics-based interpretation, actualizing a robust, universal, data-driven
      approach to problem solving, which can be applied to exploration of local
      transport and other functional phenomena in other spatially inhomogeneous
      systems. 

PMID- 24869673
TI  - Do unto others: doctors' personal end-of-life resuscitation preferences and their
      attitudes toward advance directives.
AB  - OBJECTIVE: High-intensity interventions are provided to seriously-ill patients in
      the last months of life by medical sub-specialists. This study was undertaken to
      determine if doctors' age, ethnicity, medical sub-specialty and personal
      resuscitation and organ donation preferences influenced their attitudes toward
      Advance Directives (AD) and to compare a cohort of 2013 doctors to a 1989 (one
      year before the Patient Self Determination Act in 1990) cohort to determine any
      changes in attitudes towards AD in the past 23 years. DESIGN: Doctors in two
      academic medical centers participated in an AD simulation and attitudes survey in
      2013 and their responses were compared to a cohort of doctors in 1989. OUTCOMES:
      Resuscitation and organ donation preferences (2013 cohort) and attitudes toward
      AD (1989 and 2013 cohorts). RESULTS: In 2013, 1081 (94.2%) doctors of the 1147
      approached participated. Compared to 1989, 2013 cohort did not feel that
      widespread acceptance of AD would result in less aggressive treatment even of
      patients who do not have an AD (p<0.001, AUC = 0.77); had greater confidence in
      their treatment decisions if guided by an AD (p<.001, AUC = 0.58) and were less
      worried about legal consequences of limiting treatment when following an AD
      (p<.001, AUC  = 0.57). The gender (p = 0.00172), ethnicity (chi2 14.68, DF = 3,p
      = .0021) and sub-specialty (chi2 28.92, p = .004, DF = 12) influenced their
      attitudes towards AD. 88.3% doctors chose do-not-resuscitate status and wanted to
      become organ donors. Those less supportive of AD were more likely to opt for
      "full code" even if terminally ill and were less supportive of organ donation.
      CONCLUSIONS: Doctors' attitudes towards AD has not changed significantly in the
      past 23 years. Doctors' gender, ethnicity and sub-specialty influence their
      attitudes towards AD. Our study raises questions about why doctors continue to
      provide high-intensity care for terminally ill patients but personally forego
      such care for themselves at the end of life.

PMID- 24869676
TI  - A new and fast characterization of multiple encoding properties of auditory
      neurons.
AB  - The functional properties of auditory cortex neurons are most often investigated
      separately, through spectrotemporal receptive fields (STRFs) for the frequency
      tuning and the use of frequency sweeps sounds for selectivity to velocity and
      direction. In fact, auditory neurons are sensitive to a multidimensional space of
      acoustic parameters where spectral, temporal and spatial dimensions interact. We
      designed a multi-parameter stimulus, the random double sweep (RDS), composed of
      two uncorrelated random sweeps, which gives an easy, fast and simultaneous access
      to frequency tuning as well as frequency modulation sweep direction and velocity
      selectivity, frequency interactions and temporal properties of neurons. Reverse
      correlation techniques applied to recordings from the primary auditory cortex of
      guinea pigs and rats in response to RDS stimulation revealed the variety of
      temporal dynamics of acoustic patterns evoking an enhanced or suppressed firing
      rate. Group results on these two species revealed less frequent suppression areas
      in frequency tuning STRFs, the absence of downward sweep selectivity, and lower
      phase locking abilities in the auditory cortex of rats compared to guinea pigs. 

PMID- 24869674
TI  - Risk factors for suicidal behaviour in individuals on disability pension due to
      common mental disorders - a nationwide register-based prospective cohort study in
      Sweden.
AB  - BACKGROUND: Common mental disorders (CMD) have become one of the leading causes
      for disability pension (DP). Studies on predictors of adverse health outcome
      following DP are sparse. This study aimed to examine the association of different
      socio-demographic factors and health care consumption with subsequent suicidal
      behaviour among individuals on DP due to CMD. METHOD: This is a population-based
      prospective cohort study based on register data. All individuals aged 18-64
      years, living in Sweden on 31-Dec-2004 who in 2005 were on DP due to CMD (N = 46
      745) were followed regarding suicide attempt and suicide (2006-10). Univariate
      and multivariate hazard ratios (HR) and 95% confidence intervals (CI) for
      suicidal behaviour were estimated by Cox regression. RESULTS: During the five
      year follow-up, 1 046 (2.2%) and 210 (0.4%) individuals attempted and committed
      suicide, respectively. Multivariate analyses showed that young age (18-24 years)
      and low education predicted suicide attempt, while living alone was associated
      with both higher suicide attempt and suicide (range of HRs 1.23 to 1.68).
      Combined prescription of antidepressants with anxiolytics during 2005 and
      inpatient care due to mental diagnoses or suicide attempt (2001-05) were strongly
      associated with suicide attempt and suicide (range of HRs 1.3 to 4.9), while
      inpatient care due to somatic diagnoses and specialized outpatient care due to
      mental diagnoses during 2001-05 only predicted suicide attempt (HR 1.45; 95% CI:
      1.3-1.7; HR 1.30; 95% CI: 1.1-1.7). CONCLUSIONS: Along with socio-demographic
      factors, it is very important to consider type of previous healthcare use and
      medication history when designing further research or intervention aiming at
      individuals on DP due to CMD. Further research is warranted to investigate both
      characteristics of disability pension due to CMD, like duration, diagnoses and
      grade as well as mechanisms to subsequent suicidal behavior, taking potential
      gender differences into consideration.

PMID- 24869678
TI  - Amphipoda (Crustacea) from the Chagos Archipelago.
AB  - Thirteen species of amphipods are recorded from the Chagos archipelago in the
      Indian Ocean. Of these, six species are new to science. A further four families
      (and four species) are represented, but were too incomplete to identify. 

PMID- 24869677
TI  - Aberrant protamine content in sperm and consequential implications for
      infertility treatment.
AB  - Human sperm express two types of protamine: protamine 1 (P1) and the family of
      protamine 2 (P2) proteins, with P1 and P2 normally existing in a ratio of
      approximately 1:1. Both the elevation and reduction of this ratio have been
      linked with male infertility suggesting that abnormalities in protamine
      expression, processing and replacement may be responsible for effects on semen
      parameters observed in infertile males affected by deficient protamination, along
      with abnormalities in associated regulatory processes. Abnormal protamination may
      result in insufficient condensation in the sperm nucleus, thus rendering paternal
      DNA susceptible to damage, which could have detrimental consequences upon
      embryogenesis. Consequently, it is imperative that Assisted Reproductive
      Technologies (ARTs) endeavour to utilise sperm devoid of protamine abnormalities,
      especially because retained histones are present in imprinted gene clusters.
      Emerging evidence indicates that abnormalities in protamine content may influence
      epigenetic signals transmitted via paternal DNA. Indeed, an increase in rare
      imprinting disorders has been observed in children conceived via in vitro
      fertilisation (IVF). This review examines the links between male infertility,
      abnormal protamine expression and replacement, the implications of abnormal sperm
      DNA packaging on fertility treatments and the potential iatrogenic effects of ART
      procedures on sperm function.

PMID- 24869679
TI  - A revision of the Pediacus Shuckard 1839 (Coleoptera: Cucujidae) of Asia and
      Australasia.
AB  - The Pediacus Shuckard fauna of Asia and Australasia is revised. Eighteen species
      are recorded, described and illustrated from the regions and a key to species is
      provided. Nine new species are described: Pediacus australis sp. nov. (Australia,
      Papua New Guinea, Philippines, Thailand), P. carinatus sp. nov. (Indonesia,
      Malaysia, Thailand), P. fujianensis sp. nov. (China), P. japonicoides sp. nov.
      (Taiwan); P. leei sp. nov. (Taiwan), P. pendleburyi sp. nov. (Malaysia), P.
      sinensis sp. nov. (China), P. taiwanensis sp. nov. (Taiwan) and P. thomasi sp.
      nov. (Taiwan). A checklist of the Pediacus fauna of the world is given, listing a
      total of 31 species.  

PMID- 24869680
TI  - Co-authorship networks (and other contextual factors) behind the growth of
      taxonomy of South American Ephemeroptera: a scientometric approach.
AB  - Science carried out in South America has experienced a major rise in the levels
      of productivity and impact during the last decade. The continuity of this process
      depends upon strong policy decisions of personnel training and of increasing
      investments. We study the effects of a new regional paradigm, specifically, an
      increasing international visibility through knowledge support, using the
      particular case of taxonomy of an ancient group of insects (Ephemeroptera) in
      South America. We tracked the number of new species described in scholarly papers
      along a period of two centuries. We have also mined patterns of connections from
      the respective co-authorship network. A quantitative framework to analyze
      historical sequences of scientific output is also proposed. Our results point out
      three stages of taxonomic development: (i) a pioneering stage (1800's-1970's)
      where foreign authors coming from Europe and North America account for almost the
      totality of described species, (ii) a transitional stage (1980's-1990's) where
      new species are described by both foreign and regional authors, and (iii) an
      autonomous stage (1999-present) where the bulk of scientific output is performed
      by regional authors. Remarkably, the transitional stage coincides with the advent
      of democracy in the region. We hypothesize that conjunction of funding and
      interactions between researchers act synergistically to foster an autochthonous
      taxonomy in South America. 

PMID- 24869681
TI  - Mites of the superfamily Pygmephoroidea (Acari: Heterostigmata: Neopygmephoridae,
      Pygmephoridae) associated with Trox cadaverinus (Coleoptera: Trogidae) from the
      Far East of Russia, with description of a new genus and two new species.
AB  - Three species of the superfamily Pygmephoroidea (Neopygmephoridae:
      Pygmephoridae), phoretic on Trox cadaverinus Illiger (Coleoptera: Trogidae) are
      recorded from the Far East of Russia. A new genus, Troxodania Khaustov and Trach
      gen. nov. (Neopygmephoridae), and 2 new species, Troxodania magnifica Khaustov
      and Trach sp. nov. and Pseudopygmephorellus troxi Khaustov and Trach sp. nov.
      (Pygmephoridae), are described. Bakerdania sinanii Sevastianov and Zahida Al
      Douri, 1989 (Neopygmephoridae) is considered as a junior synonym of Troxodania
      decumanus (Krczal, 1959) comb. nov. The key to genera of neopygmephorid females
      which have median genital sclerites is provided. The taxonomic significance of
      the median genital sclerite in females of the family Neopygmephoridae is
      discussed. 

PMID- 24869682
TI  - A new species of Nemacerota Hampson, [1893] (Lepidoptera, Thyatiridae) from
      Tibet, China.
AB  - The genus Nemacerota Hampson, [1893] includes 14 species worldwide, which are
      mainly distributed from Pakistan along the main Himalayan chain, the eastern
      frontier of the Tibetan plateau and the Central Chinese mountains to the northern
      Pacific regions. Ten species have been recorded from China. Among them, only N.
      tancrei (Graeser, 1888) occurs in NE China, whereas all other taxa inhabit
      mountainous areas in Central China, the eastern frontier of the Tibetan plateau
      or Tibet. N. igorkostjuki Laszlo, Ronkay, Ronkay & Witt, 2007 is found only in
      the southern edge of Tibet (Nyalam = Nielamu); N. mandibulata Laszlo, Ronkay,
      Ronkay & Witt, 2007, N. taurina Laszlo, Ronkay, Ronkay & Witt, 2007, N. stueningi
      Laszlo, Ronkay, Ronkay & Witt, 2007, N. pectinata (Houlbert, 1921), N. inouei
      Laszlo, Ronkay, Ronkay & Witt, 2007 and N. owadai Laszlo, Ronkay, Ronkay & Witt,
      2007 are known from Mt. Taibaishan, Shaanxi Province; N. griseobasalis (Sick,
      1941), N. decorata (Sick, 1941) and N. pectinata (Houlbert, 1921) occur in the
      northwestern parts of Yunnan Province (and, possibly, also in southern Sichuan).
      Here we describe a new species from the Linzhi area, Autonomous Region Xizang
      (Tibet), China. Specimens were dissected and examined using standard methods;
      adult photographs were photographed with a Nikon D700; genitalic slides were
      photographed using the Qcapture pro system, and processed in Adobe Photoshop CS5
      software. 

PMID- 24869684
TI  - Revision of African Neaspasia Diakonoff, 1989 and the related Conaspasia, n. gen.
      (Lepidoptera, Tortricidae).
AB  - The six species of Neaspasia Diakonoff present in mainland Africa are described
      and illustrated. Niphadophylax albonigra Razowski & Wojtusiak and N. sophrona
      Razowski & Wojtusiak are transferred to Conaspasia, new genus. Four new species
      are described: Neaspasia coronana Aarvik, new species, N. karischi Aarvik, new
      species, N. malamigambo Aarvik, new species, and Conaspasia congolana Aarvik, new
      species. Argyroploce orthacta Meyrick, Argyroploce brevisecta Meyrick, and
      Penthina brevibasana Walsingham are transferred to Neaspasia. Neaspasia rhodesiae
      Razowski & Brown is a junior synonym of Neaspasia orthacta (Meyrick), new
      combination. Genetancylis homalota Razowski and Rhopobota cornuta Razowski, both
      described from Oman, are transferred to Neaspasia. Genetancylis Razowski is
      synonymised with Neaspasia. 

PMID- 24869683
TI  - Three new species of Alburnoides (Teleostei: Cyprinidae) from Euphrates River,
      Eastern Anatolia, Turkey.
AB  - Three new species of Alburnoides, Alburnoides emineae sp. n., Alburnoides
      velioglui sp. n., Alburnoides recepi sp. n., are described from the Euphrates
      River drainages (Persian Gulf basin) in eastern Anatolia, Turkey. Alburnoides
      emineae, from Beyazsu Stream (south-eastern Euphrates River drainage), is
      distinguished from all species of Alburnoides in Turkey and adjacent regions by a
      combination of the following characters (none unique to the species): a well
      developed ventral keel between pelvic and anal fins, commonly scaleless or very
      rarely 1-2 scales covering the anterior portion of the keel; a deep body (depth
      at dorsal-fin origin 31-36% SL); 37-43 + 1-2 lateral-line scales, 131/2-151/2
      branched anal-fin rays; number of total vertebrae 41-42, modally 41, comprising
      20-21 abdominal and 20-21 caudal vertebrae. Alburnoides velioglui, from Sirli,
      Karasu, Divrigi and Sultansuyu streams (northern and northeastern Euphrates River
      drainages), is distinguished by a poorly developed ventral keel, completely
      scaled; a moderately deep body (depth at dorsal-fin origin 24-29% SL); 45-53 + 1
      2 lateral-line scales, 111/2 -131/2 branched anal-fin rays; number of total
      vertebrae 41-42, modally 42, comprising 20-22 abdominal and 20-21 caudal
      vertebrae. Alburnoides recepi, from Merzimen Stream (southern Euphrates River
      drainage), is distinguished by a well developed ventral keel, completely
      scaleless; a deep body (depth at dorsal-fin origin 29-34% SL); 47-56 + 2-3
      lateral-line scales; 131/2-161/2 branched anal-fin rays; number of total
      vertebrae 38-40, comprising 19-21 abdominal and 18-20 caudal vertebrae. 

PMID- 24869685
TI  - Additions to Japanagallia ishihara (Hemiptera, Cicadellidae, Megophthalminae)
      from Guizhou, and Yunnan provinces, and Guangxi autonomous region, Southwest
      China.
AB  - The (nine) valid species of Japanagallia Ishihara, 1955 from Guizhou, and Yunnan
      Provinces, and Guangxi Autonomous Region of Southwest China are reviewed and four
      new species J. gracilenta sp. nov., J. neohamata sp. nov., J. trifurcata sp. nov.
      and J. viraktamathi sp. nov. are described and illustrated. These species can be
      distinguished by unique features of the aedeagus. J. hamata Zhang & Li, 1999 is
      redescribed and illustrated based on the holotype and material from Guizhou
      Province and Guangxi Autonomous Region. A checklist and a key for identification
      of species of the genus Japanagallia are provided along with a map showing the
      distribution of Japanagallia in Guizhou, and Yunnan Provinces, and Guangxi
      Autonomous Region. 

PMID- 24869687
TI  - Descriptions of immature stages of the weevil Lixus punctiventris Boheman, 1835
      (Coleoptera, Curculionidae, Lixini).
AB  - Last instar larva of Lixus punctiventris Boheman is redescribed and illustrated,
      its pupa is described and illustrated for the first time. Biology of this species
      is analyzed in association with larval morphology and feeding habits. Overall
      larval and pupal morphological diagnoses of the genus Lixus and larval diagnosis
      of the tribe Lixini are updated. 

PMID- 24869686
TI  - Katianna maryae n. sp. (Collembola: Katiannidae), a southern Appalachian species
      of a Gondwanan genus.
AB  - Katianna maryae n. sp. is described from turf and grassy fields in eastern
      Tennessee, USA. This species is the first of its genus to be noted from temperate
      North America. It is distinguished from other described Katianna spp. by a
      combination of the following characters: color pattern of body an intricate
      mosaic of purple-brown, yellow-orange and white; copper-brown median stripe
      between eye patches; fourth antennal segment annuliform but not subsegmented;
      region between interantennal and clypeal region devoid of setae, clypeal region
      with six rows of setae; fore and middle feet with 8 clavate tenent hairs, hind
      foot with 6; apical filament of unguiculus long on fore and middle tibiotarsi,
      short on hind tibiotarsus; unguis with intricate multidentate pseudonychia;
      posterior face of dens with one proximal seta and a pair of subapical setae. 

PMID- 24869688
TI  - Two new tardigrade species from Sicily.
AB  - Two new species of tardigrades are described from Sicilian moss samples:
      Macrobiotus insuetus sp. nov. and Diphascon (Diphascon) procerum sp. nov.
      Macrobiotus insuetus sp. nov. is a species of the harmsworthi-group characterized
      by both posterior and anterior claws of the hind legs, which are different in
      shape from those of the first three leg pairs. The IV claws have extended basal
      tract where the branches are joined and the secondary branch breaks at near right
      angle to the primary branch and is clearly shorter than the main branch and the
      secondary branch of claws I-III. The eggs are not areolated and have conical
      processes with a reticular ornamentation. Diphascon (D.) procerum sp. nov. has a
      delicate cuticular ornamentation of very small tubercles, almost dots; two
      macroplacoids and septulum are present; thin accessory points are present on the
      main branches of the slender claws; lunules are absent but the base of the
      external claws of the hind legs are enlarged and slightly indented; a cuticular
      bar is present near the internal claw of the first three leg pairs and two
      cuticular bars are present on the hind legs between the base of the claws and
      near the base of the anterior claw.  

PMID- 24869689
TI  - Three new species of the genus Scaphoideus (Hemiptera: Cicadellidae) with notes
      on the female of Scaphoideus varna from India.
AB  - Three new species of leafhoppers, Scaphoideus ramamurthyi sp. nov. (from
      Meghalaya: Barapani), Scaphoideus menoni sp. nov. (from Kerala: Valluvady) and
      Scaphoideus viraktamathi sp. nov. (from Kerala: Kannavam) from India, are
      described and illustrated. Also, the female of S. varna Viraktamath & Mohan,
      previously known only from Myanmar is described with a new record for India.
      Taxonomic notes on the few cryptic species of Scaphoideus also provided. 

PMID- 24869690
TI  - Correcting the disconnect between phylogenetics and biodiversity informatics.
AB  - Rich collections of biodiversity data are now synthesized in publically available
      databases and phylogenetic knowledge now provides a sound understanding of the
      origin of organisms and their place in the tree of life. However, these knowledge
      bases are poorly linked, leading to underutilization or worse, an incorrect
      understanding of biodiversity because there is poor evolutionary context. We
      address this problem by integrating biodiversity information aggregated from many
      sources onto phylogenetic trees. PhyloJIVE connects biodiversity and phylogeny
      knowledge bases by providing an integrated evolutionary view of biodiversity data
      which in turn can improve biodiversity research and the conservation decision
      making process. Biodiversity science must assert the centrality of evolution to
      provide effective data to counteract global change and biodiversity loss. 

PMID- 24869691
TI  - Large carpenter bees in Argentina: systematics and notes on the biology of
      Xylocopa subgenus Neoxylocopa (Hymenoptera: Apidae).
AB  - A systematic revision of the species of the genus Xylocopa subgenus Neoxylocopa
      in Argentina is provided. Seven species are included: X. atamisquensis Lucia &
      Abrahamovich, X. augusti Lepeletier, X. eximia Perez, X. frontalis (Olivier), X.
      mendozana Enderlein, X. nigrocincta Smith and X. tacanensis Moure. The males of
      X. eximia and X. nigrocincta are described for the first time. Xylocopa
      jujuyensis Brethes is a new junior synonym of X. nigrocincta. Photographs,
      occurrence maps, and identification keys for the species are presented.
      Information on the nest architecture and substratum preference are also given. 

PMID- 24869692
TI  - Lost and found: the Eocene family Pyramimitridae (Neogastropoda) discovered in
      the recent fauna of the Indo-Pacific.
AB  - Most neogastropod families have a continuous record from the Cretaceous or
      Paleogene to the Recent. However, the fossil record also contains a number of
      obscure nominal families with unusual shell characters that are not adequately
      placed in the current classification. Some of these are traditionally regarded as
      valid, and some have been "lost" in synonymy. One such "lost" family is the
      Pyramimitridae, established by Cossmann in 1901 for the Eocene genus Pyramimitra,
      and currently included in the synonymy of Buccinidae. Examination of several
      species of inconspicuous, small turriform gastropods has revealed a radula type
      so far unknown in Neogastropoda, and their shell characters identify them as
      members of the "extinct" family Pyramimitridae. Neither the radular morphology
      nor the anatomy reveal the relationships of this enigmatic, "living fossil"
      family. Molecular data (12S, 16S, 28S, COI) confirm the recognition of
      Pyramimitridae as a distinct family, but no sister group was identified in the
      analysis. The family Pyramimitridae Cossmann, 1901, is thus restored as a valid
      family of Neogastropoda that includes the genera Pyramimitra Conrad, 1865,
      Endiatoma Cossmann, 1896, Vaughanites Woodring, 1928, Hortia Lozouet, 1999, and
      Teremitra new genus. Pyramimitrids occur in the Recent fauna at bathyal depths of
      the Indo-Pacific from Taiwan to Madagascar and New Zealand, with three genera and
      nine species (all but one new). 

PMID- 24869693
TI  - Redescription of the stygobitic shrimp Troglocaris (Xiphocaridinella)
      jusbaschjani Birstein, 1948 (Decapoda: Caridea: Atyidae) from Agura River, Sochi,
      Russia, with remarks on other representatives of the genus from Caucasus.
AB  - The complete re-description of Caucasian local endemic stygobitic atyid shrimp
      Troglocaris (Xiphocaridinella) jusbaschjani Birstein, 1948 is firstly presented
      after its original description given by Dr. Ya. A. Birstein (1948) under the name
      Troglocaris schmidti jusbaschjani. The species is still known exclusively from
      the type locality, hydrogen sulfide bathes of the small Agura River, Sochi area,
      Russian Federation. Remarks on morphology, coloration of both females and males
      and data on ecology of Troglocaris (Xiphocaridinella) jusbaschjani Birstein, 1948
      as well as remarks on morphology of relative congeneric species from Caucassus,
      Troglocaris (Xiphocaridinella) kutaissiana (Sadowsky, 1930) (type species of the
      subgenus) and Troglocaris (Xiphocaridinella) fagei Birstein, 1939, are provided.
      Discussion on the validity of some subgenera within the genus Troglocaris s. str.
      Dormitzer, 1853 are also presented. 

PMID- 24869694
TI  - Invalid usage of Pyrrhulopsis Reichenbach as the generic name for the Fijian
      shining parrots, Prosopeia Bonaparte, and its consequences.

PMID- 24869695
TI  - Catalogue of the world genera and subgenera of the superfamilies Derodontoidea
      and Bostrichoidea (Coleoptera: Derodontiformia, Bostrichiformia).
AB  - A catalogue of all the known genera and subgenera of the Coleoptera series
      Derodontiformia and Bostrichiformia, each with a single superfamily
      (Derodontoidea and Bostrichoidea, respectively), is provided. The following new
      tribes are established and type genera are designated: Apphianini Hava trib.
      nov., Ranolini Hava trib. nov. (all Dermestidae); Ochinini Zahradnik trib. nov.,
      Phanerochilini Zahradnik trib. nov. (all Ptinidae). The subgenus Paranovelsis has
      been removed as a synonym and has been reelevated to generic rank. The following
      new synonymies are proposed: Megatoma Herbst, 1791 (= Perimegatoma Horn, 1875
      syn. nov., Caucasotoma Mroczkowski, 1967 syn. nov.); Trinodes Dejean, 1821 (=
      Trinodus Gistl, 1856 syn. nov.); Nosodendron Latreille, 1804 (= Nosodendrium
      Gistl, 1856 syn. nov.); Casapus Wollaston, 1862 (= Pithodes Wollaston, 1862 syn.
      nov.). 

PMID- 24869696
TI  - Study of the genus Bracon Fabricius, 1804 (Hymenoptera: Braconidae) of Southern
      Iran with description of a new species.
AB  - A survey on the genus Bracon Fabricius, 1804 was conducted in Hormozgan province,
      Southern Iran, during February 2011-July 2012. In all, 19 species belonging to
      seven subgenera were collected and identified, of which seven species and the
      subgenus Asiabracon Tobias, 1957 are recorded for first time from Iran. Bracon
      (Orthobracon) persiangulfensis Ameri, Beyarslan & Talebi sp. n. is newly
      described and illustrated from the Queshm island of Persian Gulf. Morphological
      characters of the new species were compared with the congeneric species. The
      newly recorded species from Iran were as follow: B. (Asiabracon) quardrimaculatus
      Telenga, 1936; B. (Bracon) kozak Telenga, 1936; B. (Glabrobracon) immutator Nees;
      B. (Habrobracon) telengai (Mulyarskaya, 1955); B. (Habrobracon) variegator
      Spinola, 1808; B. (Orthobracon) epitriptus Marshall, 1885 and B. (Orthobracon)
      exhilarator Nees, 1834. A key is presented for identification of Bracon species
      collected in Hormozgan province as well as an updated checklist of all Bracon
      species occurring in Iran. 

PMID- 24869697
TI  - Reproductive biology of galatheoid and chirostyloid (Crustacea: Decapoda) squat
      lobsters from the Gulf of Mexico.
AB  - Reproductive timing, fecundity, and average egg sizes were examined for
      galatheoid and chirostyloid squat lobster collections from the Gulf of Mexico.
      While congeners did not always significantly differ in egg size or timing, each
      genus had a unique average egg diameter size which may indicate whether the
      developing embryos will be lecithotrophic or planktotrophic larvae. The eggs of
      Eumunididae, Galatheidae, and Munididae were more numerous and smaller than the
      larger and less abundant eggs of Chirostylidae and Munidopsidae. With the
      exception of members of the Munididae, members of genera within the same family
      had distinct egg diameters. Ovigerous females were significantly larger than non
      ovigerous females in some species (i.e., Uroptychus nitidus, Munida forceps,
      Galacantha spinosa, Munidopsis abbreviata, M. alaminos, M., erinacea, M. robusta,
      M. sigsbei, and M. simplex). Munidopsis erinacea and Munida affinis males were
      significantly larger than females; the reverse was true for Munidopsis robusta
      and Munidopsis simplex. All other species studied did not have a significant
      difference between males and females. The spatial and bathymetric ranges for many
      species are extended in this study from prior reports. Seasonality of
      reproduction was evident in few species, but this may be a result of limited
      sample sizes. 

PMID- 24869698
TI  - Review of south temperate New World Coelocybinae (Hymenoptera: Pteromalidae).
AB  - The Coelocybinae (Hymenoptera: Pteromalidae) of the southern parts of the New
      World are reviewed. Ariasina Heydon n. gen. is described for Ar. adusta Heydon n.
      sp. and Ar. gigas Heydon n. sp. Other new species described are Ambogaster karooi
      Heydon n. sp., Lanthanomyia bockleri Heydon n. sp. and L. pardos Heydon n. sp.
      Updated information on distributional records, new host plant information, and a
      key to all included genera and species of the Coelocybinae of Chile and Argentina
      are presented.  

PMID- 24869699
TI  - Taxonomy, distribution, natural history and conservation of the Russet-mantled
      Foliage-gleaner Syndactyla dimidiata (Pelzeln, 1859) (Aves: Furnariidae).
AB  - Russet-mantled Foliage-gleaner is an extremely poorly known species, the range of
      which is centered in the Brazilian Cerrado, where it inhabits riparian forests.
      Two subspecies are recognized, but the limits of their ranges are controversial.
      Furthermore, it was recently suggested that the species is one of the few in the
      family Furnariidae to show sexual dichromatism. In this paper we examined the
      plumage coloration and morphometrics of 33 study skins (85% of the available
      specimens). We conclude that the geographic variation and sexual dichromatism
      reported for S. dimidiata originated from misinterpretation of the plumage
      variation observed in this species, which is best considered monotypic. We also
      present natural history data on Russet-mantled Foliage-gleaners and suggest
      considering it a globally Vulnerable species. 

PMID- 24869700
TI  - A new Loewia Egger (Diptera: Tachinidae) from Turkey, with taxonomic and
      nomenclatural remarks on congeners.
AB  - The new species Loewia papei sp. nov. from southern Anatolia (Turkey) is
      described, illustrated and compared with congeners. A brief diagnosis of Loewia
      Egger is provided and the systematics of the genus are discussed. Loewia nudigena
      Mesnil, 1972 is fixed as the type species of Fortisia Rondani, 1861 (junior
      synonym of Loewia). A full list of previously known valid species of Loewia is
      provided along with information on primary types, type repositories (where
      known), and type localities. A lectotype is designated for Thrychogena brevifrons
      Rondani, 1856 (= Loewia brevifrons (Rondani, 1856)). 

PMID- 24869701
TI  - Periclimenaeus species (Crustacea: Decapoda: Pontoniinae) from Hawaii.
AB  - Two specimens of an undescribed species of pontoniine shrimp of the genus
      Periclimenaeus Borradaile 1915 from Maui Island, Hawaiian Islands, are described
      and illustrated, raising to three the number of species known from the Hawaiian
      Islands. The new species is remarkable for the greatly reduced molar process and
      sharp lateral cutting edge on the major second pereiopod dactyl and most closely
      resembles P. tchesunovi Duris, 1990. Host animals not identified. Periclimenaeus
      devaneyi Bruce, 2010 also has its colouration described for the first time. 

PMID- 24869702
TI  - A checklist of the millipedes (Diplopoda) of Laos.
AB  - At the present, the millipede fauna of Laos comprises only 34 species from 20
      genera, 13 families and 7 orders. These counts certainly represent but a minor
      fraction of the country's real diversity of Diplopoda even at the ordinal level,
      let alone at lower ones. Based on the available information from the adjacent
      parts of China, Thailand, Myanmar, Vietnam and/or Cambodia, the orders
      Polyxenida, Sphaerotheriida, Chordeumatida, Julida and Polyzoniida must occur in
      Laos, may be also Glomeridesmida, Siphonocryptida and Stemmiulida, but none has
      been recorded there yet. Moreover, even some ubiquitous "tramp" species, such as
      Glyphiulus granulatus (Gervais, 1847), Trigoniulus corallinus (Gervais, 1847),
      Desmoxytes planata (Pocock, 1895) or Oxidus gracilis (C. L. Koch, 1847), have
      hitherto not been found in Laos. This shows that a lot more collecting efforts,
      which have heretofore been rather strongly biased to caves, are required to amass
      a representative material of Diplopoda of Laos and make it available for study. 

PMID- 24869703
TI  - New subgenus and new species Nousia (Araucophlebia) latifolia subgen. n. et sp.
      n. (Ephemeroptera: Leptophlebiidae) from Chile.
AB  - A new subgenus and new species, Nousia (Araucophlebia) latifolia subgen. et
      sp.n., are described from the Maule and Araucania regions in Chile, based on male
      and female imagos reared from larvae. This species has unusual shapes of larval
      tergalii, male imaginal genitalia and flat eggs. 

PMID- 24869704
TI  - Apterogyninae (Hymenoptera: Bradynobaenidae) from Saudi Arabia, with description
      of a new species.
AB  - Eleven species in three genera from Saudi Arabia are listed. Macroocula riyadha
      Gadallah & Pagliano, spec. nov. is described and figured. Apterogyna mateui Giner
      Mari, 1945, Macroocula nitida nitida (Bischoff, 1920) are newly recorded from
      Arabian Peninsula and Saudi Arabia, Macroocula magna (Invrea, 1965) is newly
      recorded from Saudi Arabia. 

PMID- 24869705
TI  - Nomenclature, lectotype designation and type locality restriction for
      Amietophrynus mauritanicus (Schlegel, 1841) (Anura, Bufonidae).

PMID- 24869706
TI  - The subgenus Choeras Mason, 1981 of genus Apanteles Foerster, 1862 (Hymenoptera,
      Braconidae, Microgastrinae) from China, with descriptions of eighteen new
      species.
AB  - The subgenus Choeras Mason, 1981 of genus Apanteles Foerster, 1862 (Hymenoptera,
      Braconidae, Microgastrinae) from China is revised with 18 new species described
      and illustrated, and one known species redescribed. A key to the Chinese species
      of this subgenus is provided. 

PMID- 24869707
TI  - Four Pseudopoda species (Araneae: Sparassidae) from Southern China.
AB  - Four species of the genus Pseudopoda are recorded from southern China. Three new
      species are described: Pseudopoda bicruris sp. nov. (male, female; Hainan
      Province), Pseudopoda mediana sp. nov. (male, female; Hainan Province),
      Pseudopoda tiantangensis sp. nov. (male, female; Hubei Province). The female of
      Pseudopoda lushanensis (Wang, 1990) from Jiangxi Province is described for the
      first time. 

PMID- 24869708
TI  - Three new species and new records of the orb-weaving spider genus Philoponella
      (Araneae, Uloboridae) from Brazil and Ecuador.
AB  - Three new species of the spider genus Philoponella Mello-Leitao, 1917 are
      described: Philoponella opelli n. sp. from Brazil and Ecuador, and Philoponella
      fluviidulcifis n. sp. , and Philoponella duopunctata n. sp. from Brazil. New
      records for Philoponella vittata (Keyserling, 1881), P. republicana (Simon,
      1891), P. fasciata (Mello-Leitao, 1917) and P. divisa Opell, 1979 are provided
      for Brazil and Ecuador. 

PMID- 24869709
TI  - Sedlacekvia kinchegaensis, a new species of a charismatic genus from Australia,
      with notes on its systematics (Coleoptera, Cleridae).
AB  - Sedlacekvia kinchegaensis sp. nov., a new member of the hitherto monotypic genus
      Sedlacekvia Winkler, 1989 is described from an arid region of New South Wales,
      Australia. As the genus has not been associated with any subfamily of Cleridae
      yet, its classification within Clerinae and phylogenetic relation with
      Odontophlogistus Elston, 1923 (Cleridae: Clerinae) is proposed. 

PMID- 24869710
TI  - A pictorial key to the species of Aedes (Ochlerotatus and Coetzeemyia) in the
      Afrotropical Region (Diptera: Culicidae).
AB  - Six species of the subgenus Ochlerotatus and one species of the subgenus
      Coetzeemyia of the genus Aedes in the Afrotropical Region are treated in a
      pictorial key based on diagnostic morphological features. Brief remarks on the
      new reclassification of the genus Aedes are also included. 

PMID- 24869712
TI  - Man-made cytotoxic steroids: exemplary agents for cancer therapy.

PMID- 24869713
TI  - Apremilast (otezla) for psoriatic arthritis.

PMID- 24869714
TI  - Eslicarbazepine acetate (aptiom) for epilepsy.

PMID- 24869711
TI  - A meta-analysis of cognitive functions in children and adolescents with major
      depressive disorder.
AB  - The cumulative prevalence rates of major depressive disorders (MDD) in children
      and adolescents averages 9.5 %. The majority of adults with MDD suffer from
      significant cognitive deficits, but the available neuropsychological data on the
      cognitive performance of children and adolescents with MDD yielded mixed results.
      Meta-analytic methods were used to assess the severity of cognitive deficits in
      children and adolescents with MDD as compared to healthy children and
      adolescents. We identified 17 studies comparing the intelligence, executive
      functions, verbal memory and attention of 447 patients with DSM-IV MDD and 1,347
      healthy children and adolescents. Children and adolescents with MDD performed
      0.194-0.772 (p < 0.001) standard mean differences worse than healthy control
      subjects in neuropsychological test procedures. The most pronounced deficits of
      children and adolescents with MDD were seen in inhibition capacity (STD = 0.772;
      p = 0.002), phonemic verbal fluency (STD = 0.756; p = 0.0001), sustained
      attention (STD = 0.522; p = 0.000), verbal memory (STD = 0.516; p = 0.0009) and
      planning (STD = 0.513; p = 0.014). We revealed cognitive deficits of children and
      adolescents with MDD in various cognitive domains. Long-term studies should
      investigate how the cognitive deficits of depressed youth affect their academic
      and social functioning, and whether age, comorbidity and depression severity play
      a role in this process.

PMID- 24869716
TI  - In brief: heptavalent botulism antitoxin.

PMID- 24869715
TI  - Sorafenib (Nexavar) for thyroid cancer.

PMID- 24869718
TI  - Risk of serious opportunistic infections after solid organ transplantation:
      interleukin-2 receptor antagonists versus polyclonal antibodies. A meta-analysis.
AB  - BACKGROUND: We aimed to evaluate and quantify the risk of serious opportunistic
      infections after induction with polyclonal antibodies versus IL-2 receptor
      antagonists (IL-2RAs) in randomized clinical trials. METHODS: PRISMA guidelines
      were followed and random-effects models were performed. RESULTS: 70 randomized
      clinical trials (10,106 patients) were selected: 36 polyclonal antibodies (n =
      3377), and 34 IL-2RAs (n = 6729). Compared to controls, polyclonal antibodies
      showed higher risk of serious opportunistic infections (OR: 1.93, 95% CI: 1.34
      2.80; p < 0.0001); IL-2RAs were associated with lower risk of serious
      opportunistic infections (OR: 0.80, 95% CI: 0.68-0.94; p = 0.009). Polyclonal
      antibodies were associated with higher risk of bacterial (OR: 1.58, 95% CI: 1.00
      2.50; p = 0.049) and viral infections (OR: 2.37, 95% CI: 1.60-3.49; p < 0.0001),
      while IL-2RAs were associated with lower risk of cytomegalovirus (CMV) disease
      (OR: 0.73, 95% CI: 0.56-0.97; p = 0.032). Adjusted indirect comparison: compared
      to polyclonal antibodies, IL-2RAs were associated with lower risk of serious
      opportunistic infections (OR: 0.41, 95% CI: 0.34-0.49; p < 0.0001), bacterial
      infections (OR: 0.51, 95% CI: 0.39-0.67; p < 0.0001) and CMV disease (OR: 0.58,
      95% CI: 0.34-0.98; p = 0.043). Results remained consistent across allografts.
      CONCLUSION: The risk of serious opportunistic infections, bacterial infections
      and CMV disease were all significantly decreased with IL-2RAs compared to
      polyclonal antibodies.

PMID- 24869719
TI  - Breakdown of Richardson's law in electron emission from individual self-Joule
      heated carbon nanotubes.
AB  - Probing the validity of classical macroscopic physical laws at the nanoscale is
      important for nanoscience research. Herein, we report on experimental evidence
      that electron emission from individual hot carbon nanotubes (CNTs) heated by self
      Joule-heating does not obey Richardson's law of thermionic emission. By using an
      in-situ multi-probe measurement technique, electron emission density (J) and
      temperature (T) of individual self-Joule-heated CNTs are simultaneously
      determined. Experimental ln(J/T(2)) - 1/T plots are found to exhibit an upward
      bending feature deviating from the straight lines in Richardson plots, and the
      measured electron emission density is more than one order of magnitude higher
      than that predicted by Richardson's law. The breakdown of Richardson's law
      implies a much better electron emission performance of individual CNTs as
      compared to their macroscopic allotropes and clusters, and the need of new
      theoretical descriptions of electron emission from individual low-dimensional
      nanostructures. 

PMID- 24869717
TI  - Efficacy and safety of cilostazol based triple antiplatelet treatment versus dual
      antiplatelet treatment in patients undergoing coronary stent implantation: an
      updated meta-analysis of the randomized controlled trials.
AB  - The aim of this study was to obtain best estimates of the efficacy and safety of
      cilostazol-based triple antiplatelet therapy (TAPT: aspirin, clopidogrel and
      cilostazol) compared with dual antiplatelet therapy (DAPT: aspirin and
      clopidogrel) in patients undergoing coronary stent implantation. We searched the
      literature to identify all randomized clinical trials examining efficacy and
      safety of TAPT versus DAPT in patients undergoing coronary stent implantation.
      Major efficacy outcomes were death, non-fatal myocardial infarction (MI),
      ischemic stroke and stent thrombosis (ST) and the safety outcome was bleeding.
      Data were analyzed using the Review Manager 5.0.0 software. A total of 19 trials
      involving 7,464 patients were included. TAPT and DAPT were associated with
      similar rates of death, non-fatal MI, ischemic stroke and ST, but compared with
      DAPT, TAPT had lower rates of target lesion revascularization (TLR) (RR 0.67, 95
      % CI 0.56-0.82, P < 0.0001) and target vessel revascularization (TVR) (RR 0.65,
      95 % CI 0.55-0.77, P < 0.00001), as well as less late loss of minimal lumen
      diameter (mean difference -0.14, 95 % CI -0.17--0.11, P < 0.00001), and less
      binary angiographic restenosis (RR 0.54, 95 % CI 0.45-0.65, P < 0.00001). TAPT
      and DAPT had similar rates of bleeding, but TAPT had significantly higher rates
      of headache, palpitation, rash and gastrointestinal side-effects. Cilostazol
      based TAPT compared with DAPT is associated with improved angiographic outcomes
      and decreased risk of TLR and TVR but does not reduce major cardiovascular events
      and is associated with an increase in minor adverse events. 

PMID- 24869720
TI  - Embracing oral cholera vaccine--shifting response to cholera.

PMID- 24869721
TI  - Use of Vibrio cholerae vaccine in an outbreak in Guinea.
AB  - BACKGROUND: The use of vaccines to prevent and control cholera is currently under
      debate. Shanchol is one of the two oral cholera vaccines prequalified by the
      World Health Organization; however, its effectiveness under field conditions and
      the protection it confers in the first months after administration remain
      unknown. The main objective of this study was to estimate the short-term
      effectiveness of two doses of Shanchol used as a part of the integrated response
      to a cholera outbreak in Africa. METHODS: We conducted a matched case-control
      study in Guinea between May 20 and October 19, 2012. Suspected cholera cases were
      confirmed by means of a rapid test, and controls were selected among neighbors of
      the same age and sex as the case patients. The odds of vaccination were compared
      between case patients and controls in bivariate and adjusted conditional logistic
      regression models. Vaccine effectiveness was calculated as (1-odds ratio)*100.
      RESULTS: Between June 8 and October 19, 2012, we enrolled 40 case patients and
      160 controls in the study for the primary analysis. After adjustment for
      potentially confounding variables, vaccination with two complete doses was
      associated with significant protection against cholera (effectiveness, 86.6%; 95%
      confidence interval, 56.7 to 95.8; P=0.001). CONCLUSIONS: In this study, Shanchol
      was effective when used in response to a cholera outbreak in Guinea. This study
      provides evidence supporting the addition of vaccination as part of the response
      to an outbreak. It also supports the ongoing efforts to establish a cholera
      vaccine stockpile for emergency use, which would enhance outbreak prevention and
      control strategies. (Funded by Medecins sans Frontieres.).

PMID- 24869722
TI  - Traumatic intracranial hypertension.

PMID- 24869723
TI  - Images in clinical medicine. Metastasis from thyroid carcinoma.

PMID- 24869724
TI  - Case records of the Massachusetts General Hospital. Case 17-2014. A 64-year-old
      man with chest pain and a pleural effusion.

PMID- 24869725
TI  - When cancer co-opts the vasculature.

PMID- 24869726
TI  - Sentinel-node biopsy in melanoma.

PMID- 24869727
TI  - Sentinel-node biopsy in melanoma.

PMID- 24869728
TI  - Sentinel-node biopsy in melanoma.

PMID- 24869729
TI  - Management of early prostate cancer.

PMID- 24869730
TI  - Management of early prostate cancer.

PMID- 24869731
TI  - Management of early prostate cancer.

PMID- 24869732
TI  - Management of early prostate cancer.

PMID- 24869733
TI  - Bleeding and coagulopathies in critical care.

PMID- 24869734
TI  - Bleeding and coagulopathies in critical care.

PMID- 24869735
TI  - Bleeding and coagulopathies in critical care.

PMID- 24869736
TI  - Bleeding and coagulopathies in critical care.

PMID- 24869737
TI  - PICC placement in the neonate.

PMID- 24869738
TI  - PICC placement in the neonate.

PMID- 24869739
TI  - Pulmonary fibrosis associated with aluminum trihydrate (Corian) dust.

PMID- 24869740
TI  - Pulmonary fibrosis associated with aluminum trihydrate (Corian) dust.

PMID- 24869741
TI  - Images in clinical medicine. Gastric emphysema.

PMID- 24869742
TI  - Role of microRNAs in biotic and abiotic stress responses in crop plants.
AB  - MicroRNAs (miRNAs) are small non-coding endogenous RNAs (18-24 nucleotides) which
      regulate gene expression at posttranscriptional level either by degrading the
      target mRNA (plants) or by blocking the protein translation through binding with
      3' UTR of the target mRNA (animals). Though miRNAs are known to play key roles in
      animal development, miRNAs that are involved in plant developmental timing, cell
      proliferation, and several other physiological functions need to be investigated.
      In addition, plant miRNAs have been shown to be involved in various biotic
      (bacterial and viral pathogenesis) and abiotic stress responses such as
      oxidative, mineral nutrient deficiency, drought, salinity, temperature, cold
      (chilling), and other abiotic stress. miRNA expression profiling reveals that
      miRNAs which are involved in the progression of plant growth and development are
      differentially expressed during abiotic stress responses. The high-throughout
      techniques can provide genome-wide identification of stress-associated miRNAs
      under various abiotic stresses in plants. Various web-based and non-web-based
      computational tools facilitate in the identification and characterization of
      biotic/abiotic stress associated miRNAs and their target genes. In the future,
      miRNA-mediated RNA interference (RNAi) approach might help in developing
      transgenic crop plants for better crop improvement by conferring resistance
      against biotic (pathogens) as well as abiotic stress responses. 

PMID- 24869743
TI  - Classification of DNA minor and major grooves binding proteins according to the
      NLSs by data analysis methods.
AB  - High-mobility group proteins are a superfamily of DNA-binding proteins that bind
      to the DNA minor groove and bend it, whereas most of the transcription factors
      such as centromere protein B (CENP-B), octamer (Oct)-1, growth factor
      independence 1 (Gfi-1), and WRKY bind to the major groove of DNA. Classification
      of proteins using their DNA-binding features is the aim of this study. Nuclear
      localization signals play more important roles in entering DNA-binding proteins
      to nucleus and doing their functions; therefore, they have been considered as a
      feature which is important for DNA-binding manner in proteins. Nuclear
      localization signals (NLSs) were predicted by two prediction web servers, and
      then, their sequence ordered features were extracted by Chou's pseudo amino acid
      composition (PseAAC) and ProtParam. Multilayer perceptron was used as an
      artificial neural network for analyzing the features by calculating the
      correlation coefficient and 30-fold cross-validation. Another used data-analyzing
      program was principal component analysis of the Minitab software. By calculating
      the eigenvalues and considering five principal components, the sequence length of
      NLSs was known as the best feature for classifying DNA-binding proteins. Minimum
      mean squared error (MSE) (0.1098) and the highest R (2) (0.963) mean that there
      is a significant difference between the NLS length of the DNA major groove and
      minor groove binder proteins. Results showed that it is possible to classify DNA
      major groove and minor groove binder proteins by their NLS sequences as a
      feature. 

PMID- 24869744
TI  - Response of gelatin modified electrode towards sensing of different metabolites.
AB  - In this study, a very thin film of biocompatible gelatin B (GB) fabricated onto
      indium tin oxide (ITO)-coated glass substrate for electrochemical catalytic
      activity towards different metabolites has been investigated. The optical and
      electrochemical properties of bare GB/ITO electrode and with different
      metabolites were characterized by scanning electron microscopy (SEM), Fourier
      transform infrared spectroscopy (FTIR) and electrochemical techniques. The
      optical properties clearly indicate the structural and surface morphological
      changes on electrode surface. FTIR spectra showed displacement of the IR peaks
      towards smaller wave numbers, indicating possible existence of hydrogen bonding
      between the GB and metabolites. The catalytic behaviour of GB/ITO electrode
      towards ascorbic acid (AA), citric acid (CA), oxalic acid (OA), glucose (Glu),
      sucrose (Suc), lactose (Lac) and fructose (Fru) has been investigated by cyclic
      voltammetry (CV). The electrochemical response studies of GB/ITO electrode have
      been monitored with different metabolites in the range of 10-500 mg/dl. The
      sensitivity of GB/ITO electrode for AA and OA was found as 0.156 and 0.108
      MUA/(mg/dl cm(-2)) respectively. The results indicate that the GB/ITO electrode
      has higher specificity towards the AA and OA. The attractive properties of GB/ITO
      electrode provide the potential applications in the simultaneous detection of AA
      and OA. The excellent electrocatalytic behaviour of GB/ITO electrode may be
      useful towards the construction of electrochemical biosensors. 

PMID- 24869745
TI  - Revision of the genus Polymerus (Heteroptera: Miridae) in the Eastern Hemisphere.
      Part 1: Subgenera Polymerus, Pachycentrum subgen. nov. and new genus
      Dichelocentrum gen. nov.
AB  - The paper represents the first part of a series dealing with the Eastern
      Hemisphere species of the genus Polymerus Hahn, 1831 and includes a redescription
      of the genus and the nominative subgenus, and descriptions of Pachycentrum
      subgen. nov., P. (Polymerus) russatus sp. nov. and P. (Pachycentrum) unciniger
      sp. nov. The specific name P. funestus Reuter, 1906 is transferred from the
      subgenus Poeciloscytus Fieber, 1858 to the nominative subgenus and synonymised
      with P. pekinensis Horvath, 1901. New combinations for seven African, Indian, and
      Australian species are proposed: Charagochilus aureus (Ballard, 1927) comb. nov.,
      Ch. bimaculatus (Poppius, 1910) comb. nov., Ch. consanguineus (Distant, 1904)
      comb. nov., Ch. flavipes (Distant, 1904) comb. nov., Ch. madagascariensis
      (Poppius, 1914) comb. nov., Ch. obscuratus (Poppius, 1914) comb. nov.,
      Proboscidocoris solitus (Walker, 1873) comb. nov. The species Polymerus nitidus
      (Odhiambo, 1959) is returned to the genus Proboscidocoris. Five African and
      Arabian species are included in the new genus Dichelocentrum gen. nov.: D.
      alkadanum (Linnavuori & van Harten, 2005) comb. nov., D. flora (Linnavuori & van
      Harten, 2005) comb. nov., D. longirostre (Reuter, 1905) comb. nov., D.
      ornatifrons (Odhiambo, 1959) comb. nov. and D. transvaalicum sp. nov. The
      specific name Polymerus xerophilus Linnavuori, 1975 syn. nov. is synonymised with
      D. ornatifrons comb. nov. Key, diagnoses, data on distribution, and illustrations
      of the parameres, entirely inflated vesica and the gynatrium are provided for all
      recognised species from the subgenera Polymerus, Pachycentrum subgen. nov. and
      the genus Dichelocentrum gen. nov. 

PMID- 24869746
TI  - A taxonomic monograph of the genus Tylodinus Champion (Coleoptera: Curculionidae:
      Cryptorhynchinae: Tylodina) of Chiapas, Mexico.
AB  - The species of the genus Tylodinus from the Mexican state of Chiapas are revised.
      We examined 989 specimens representing 36 species; 23 species are grouped into
      eight species groups with 13 species considered as Incertae sedis. A total of 32
      species are described as new and one species is a new record for Mexico. Species
      groups  (numbers of species in parentheses) and species are: Tylodinus buchanani
      species group (6) T. buchanani new species (type locality: Chiapas, Union Juarez,
      Volcan Tacan), T. exiguus new species (type locality: Chiapas, Motozintla, 7 km
      SSW Motozintla de Mendoza), T. ixchel new species (type locality: Chiapas, Union
      Juarez, Volcan Tacan), T. jonesi new species (type locality: Chiapas, Angel
      Albino Corzo, Reserva de la Biosfera el Triunfo, Campamento el Quetzal), T.
      variabilis new species (type locality: Chiapas, San Cristobal de las Casas, Cerro
      Huitepec), T. wibmeri new species (type locality: Chiapas, Motozintla, 7 km SSW
      Motozintla de Mendoza); Tylodinus canaliculatus species group (3) T.
      canaliculatus Champion (Chiapas, Union Juarez, Volcan Tacan, new record for 
      Mexico), T. sepulturaensis new species (Type locality: Chiapas, Villa Corzo,
      Ejido Sierra Morena), T. triumforium new species (Type locality: Chiapas, La
      Concordia, 4 km SE Custepec); Tylodinus cavicrus species group (3) T. cavicrus
      Champion, T. pseudocavicrus new species (type locality: Chiapas, San Cristobal de
      las Casas, Cerro Huitepec), T. rugosus new species (type locality: Chiapas, Villa
      Flores, Sierra Morena); Tylodinus coapillensis species group (2) T. coapillensis
      new species (type locality: Chiapas, Coapilla, ca. 10.5 km NE Coapilla), T.
      leoncortesi new species (type locality: Chiapas, Pueblo Nuevo Solistahuacan, La
      Yerbabuena); Tylodinus mutabilis species group (2) Tylodinus mutabilis new
      species (type locality: Chiapas, Villa Corzo, Ejido Sierra Morena), T. parvus new
      species (type locality: Chiapas, Trinitaria, Lagunas de Montebello); Tylodinus
      nodulosus species group (3) T. andersoni new species (Chiapas, Angel Albino
      Corzo, Reserva El Triunfo, Poligono 1), T. nodulosus (Boheman), T. zilchi
      Kuschel; Tylodinus pusillus species group (2) T. porvenirensis new species (type
      locality: Chiapas, El Porvenir, El Porvenir (2 km NE)), T. pusillus new species
      (type locality: Chiapas, 4 km SE Custepec); Tylodinus spiniventris species group
      (2) T. lum new species (Chiapas, San Cristobal de las Casas, Cerro Huitepec), and
      T. spiniventris new species (type locality: Chiapas, San Cristobal de las Casas,
      Reserva Huitepec); Incertae sedis (13) T. pinguis new species (type locality:
      Chiapas, Angel Albino Corzo, Reserva El Triunfo, Poligono 1) , T. kissingeri new
      species (type locality: Chiapas, Tapalapa, ca. 14 km NE Coapilla), T. complicatus
      new species (type locality: Chiapas, Pueblo Nuevo Solistahuacan, La Yerbabuena),
      T. dominicus new species (type locality: Chiapas, Villa Corzo, Reserva de la
      Biosfera La Sepultura), T. noctis new species (type locality: Chiapas, Coapilla,
      ca. 10.5 km NE Coapilla), T. rufus new species (type locality: Chiapas, San
      Cristobal de las Casas, Cerro Huitepec); T. branstetteri new species (type
      locality: Chiapas, La Concordia, 4 km SE Custepec), T. kuscheli new species (type
      locality: Chiapas, Villa Flores, Ejido Sierra Morena), T. pappi new species (type
      locality: Chiapas, Union Juarez, Volcan Tacan), T. gibbosus new species (type
      locality: Chiapas, Pueblo Nuevo Solistahuacan, Yerbabuena Reserve), T. immundus
      new species (type locality: Chiapas, San Cristobal de las Casas Cerro Huitepec),
      T. intzin new species (type locality: Chiapas, Tenejapa, Yashanal), T. elongatus
      new species (type locality: Chiapas, Angel Albino Corzo, Reserva El Triunfo,
      Poligono 1). Three species (T. nodulosus (Boheman), T. zilchi Kuschel and T.
      cavicrus Champion) are not known to occur in Chiapas but were included in this
      study to be more representative of inter- and intraspecific variation and to
      provide a better definition of the taxonomic limits of species and species
      groups. Species groups are characterized and taxonomic composition and general
      distribution and ecological correlates summarized. Diagnoses and distributions
      are given for all species and ecological information is presented where
      available. Immature stages, life history and food habits are not known for any of
      the species.  

PMID- 24869747
TI  - Euophryine jumping spiders of the Afrotropical Region-new taxa and a checklist
      (Araneae: Salticidae: Euophryinae).
AB  - Two new genera, Rumburak gen. nov. and Yimbulunga gen. nov., of euophryine
      jumping spiders are established from the Afrotropical Region. Thirty three new
      species included in this subfamily are diagnosed and described: Chinophrys
      trifasciata sp. nov. (?, South Africa), Euophrys bifida sp. nov. (??, South
      Africa), E. cochlea sp. nov. (??, South Africa), E. elizabethae sp. nov. (??,
      South Africa), E. falciger sp. nov. (??, South Africa), E. gracilis sp. nov. (??,
      Lesotho, South Africa), E. griswoldi sp. nov. (?, Namibia), E. limpopo sp. nov.
      (?, South Africa), E. maseruensis sp. nov. (?, Lesotho), E. meridionalis sp. nov.
      (??, South Africa), E. miranda sp. nov. (?, South Africa), E. nana sp. nov. (?,
      South Africa), E. recta sp. nov. (?, South Africa), E. subtilis sp. nov. (??,
      South Africa), Rumburak bellus sp. nov. (?, South Africa), R. hilaris sp. nov.
      (??, South Africa), R. lateripunctatus sp. nov. (??, South Africa), R. mirabilis
      sp. nov. (??, South Africa), R. tuberatus (?, South Africa), R. virilis (??,
      South Africa), Tanzania parvulus sp. nov. (??, South Africa), T. striatus sp.
      nov. (??, South Africa), Thyenula alotama sp. nov. (??, South Africa), T.
      cheliceroides sp. nov. (?, South Africa), T. clarosignata sp. nov. (??, South
      Africa), T. dentatidens sp. nov. (?, South Africa), T. haddadi (??, South
      Africa), T. montana sp. nov. (?, Lesotho), T. rufa sp. nov. (??, South Africa),
      T. tenebrica sp. nov. (?, South Africa), T. virgulata sp. nov. (?, South Africa),
      T. vulnifica sp. nov. (??, South Africa) and Yimbulunga foordi sp. nov. (?, South
      Africa). Two species names are newly synonymized: Thyenula hortensis Wesolowska &
      Cumming, 2008 with T. munda (Peckham & Peckham, 1903) and Thyenula nelshoogte
      Zhang & Maddison, 2012 with T. laxa Zhang & Maddison, 2012.  Three new
      combinations are proposed: Heliophanus kittenbergeri (Caporiacco, 1947) (ex
      Euophrys), Rumburak laxus (Zhang & Maddison, 2012) (ex Thyenula) and Thyenula
      munda (Peckham & Peckham, 1903) (ex Saitis). Two names are recognized as nomina
      dubia: Euophrys nigrescens Caporiacco, 1940 and Saitis magnus Caporiacco, 1947.
      The first member of the genus Chinophrys Zhang & Maddison, 2012 is reported from
      Africa. The males of Euophrys leipoldti Peckham & Peckham, 1903 and Thyenula
      sempiterna Wesolowska, 2000 are described for the first time. Tanzania minutus
      (Wesolowska & Russell-Smith, 2000) is recorded from South Africa for the first
      time. A list of valid species of Afrotropical Euophryinae with data on their
      distribution in the region is provided. A key is supplied for the known genera of
      the region (based on males).  

PMID- 24869748
TI  - Ethnic differences in ATP-binding cassette transporter, sub-family G, member 2
      (ABCG2/BCRP): genotype combinations and estimated functions.
AB  - ATP-binding cassette transporter, sub-family G, member 2 (ABCG2/BCRP) is a
      xenobiotic transporter and also regulates serum uric acid levels as a urate
      transporter. We have shown that the severity of ABCG2 dysfunction can be
      estimated by simple genotyping of two dysfunctional variants, Q126X (rs72552713)
      and Q141K (rs2231142). This genotyping method is widely accepted for the risk
      analysis of hyperuricemia/gout, but there is no report on ethnic differences in
      ABCG2 dysfunctions. Here, we estimated ABCG2 dysfunctions by its genotype
      combination (Q126X and Q141K) and compared them in three different ethnic groups
      (500 Japanese, 200 Caucasians and 100 African-Americans). The minor allele
      frequencies of Q126X and Q141K in Japanese (0.025 and 0.275, respectively) were
      significantly higher than those in Caucasians (0.005 and 0.085, respectively) and
      African-Americans (0 and 0.090, respectively). Additionally, the rates of mild,
      moderate and severe ABCG2 dysfunctions in Japanese (35.4%, 12.4% and 1.6%,
      respectively) were higher than those in Caucasians (14.0%, 2.5% and 0%,
      respectively) and African-Americans (14.0%, 2.0% and 0%, respectively). Because
      ABCG2 dysfunctional diplotypes were commonly observed in both Caucasians (16.5%)
      and African-Americans (16.0%), the genotyping of the two ABCG2 dysfunctional
      variants is useful for evaluating individual differences in the ABCG2 dysfunction
      which affect the pharmacokinetics of substrate drugs and hyperuricemia risk in
      all three ethnic groups.

PMID- 24869749
TI  - Urinary zearalenone measured with ELISA as a biomarker of zearalenone exposure in
      pigs.
AB  - The suitability to assess zearalenone (ZEA) exposure in pigs of a commercial
      ELISA kit for ZEA analysis in urine was tested. A daily dose of 0, 5, 10, 20 and
      40 MUg synthetic ZEA per kilogram BW was administered via the feed to four gilts
      per dose group, and after 3 and after 7 days of ZEA intake, urine samples were
      assayed with the ELISA which has a relative cross-reactivity of 42% with alpha
      zearalenol. The concentration of urinary ZEA equivalents (ZEA plus 42% of alpha
      zearalenol present) did not differ between day 4 and day 8 (P = 0.50) within each
      dose group. The urinary ZEA equivalent/creatinine ratio was tightly correlated
      with ZEA intake (r = 0.95). The urinary ZEA equivalent/creatinine values at 0 and
      40 MUg/kg BW were distinctly different from those of the intermediate dose
      levels, whereas there was some overlapping of the individual values at the dose
      levels 5, 10 and 20 MUg/kg BW. The urinary ZEA equivalent/creatinine ratio can be
      used as a biomarker for ZEA exposure in pigs provided that urine samples of
      several animals receiving the same diet are assayed, either separately or after
      pooling.

PMID- 24869750
TI  - Blood pressure-lowering efficacy of monotherapy with thiazide diuretics for
      primary hypertension.
AB  - BACKGROUND: Hypertension is a modifiable cardiovascular risk factor. Although it
      is established that low-dose thiazides reduce mortality as well as cardiovascular
      morbidity, the dose-related effect of thiazides in decreasing blood pressure has
      not been subject to a rigorous systematic review. It is not known whether
      individual drugs within the thiazide diuretic class differ in their blood
      pressure-lowering effects and adverse effects. OBJECTIVES: To determine the dose
      related decrease in systolic and/or diastolic blood pressure due to thiazide
      diuretics compared with placebo control in the treatment of patients with primary
      hypertension. Secondary outcomes included the dose-related adverse events leading
      to patient withdrawal and adverse biochemical effects on serum potassium, uric
      acid, creatinine, glucose and lipids. SEARCH METHODS: We searched the Cochrane
      Central Register of Controlled Trials (CENTRAL 2014, Issue 1), Ovid MEDLINE (1946
      to February 2014), Ovid EMBASE (1974 to February 2014) and ClinicalTrials.gov.
      SELECTION CRITERIA: We included double-blind, randomized controlled trials (RCTs)
      comparing fixed-dose thiazide diuretic monotherapy with placebo for a duration of
      3 to 12 weeks in the treatment of adult patients with primary hypertension. DATA
      COLLECTION AND ANALYSIS: Two authors independently screened articles, assessed
      trial eligibility, extracted data and determined risk of bias. We combined data
      for continuous variables using a mean difference (MD) and for dichotomous
      outcomes we calculated the relative risk ratio (RR) with 95% confidence interval
      (CI). MAIN RESULTS: We included 60 randomized, double-blind trials that evaluated
      the dose-related trough blood pressure-lowering efficacy of six different
      thiazide diuretics in 11,282 participants treated for a mean duration of eight
      weeks. The mean age of the participants was 55 years and baseline blood pressure
      was 158/99 mmHg. Adequate blood pressure-lowering efficacy data were available
      for hydrochlorothiazide, chlorthalidone and indapamide. We judged 54 (90%)
      included trials to have unclear or high risk of bias, which impacted on our
      confidence in the results for some of our outcomes.In 33 trials with a baseline
      blood pressure of 155/100 mmHg, hydrochlorothiazide lowered blood pressure based
      on dose, with doses of 6.25 mg, 12.5 mg, 25 mg and 50 mg/day lowering blood
      pressure compared to placebo by 4 mmHg (95% CI 2 to 6, moderate-quality
      evidence)/2 mmHg (95% CI 1 to 4, moderate-quality evidence), 6 mmHg (95% CI 5 to
      7, high-quality evidence)/3 mmHg (95% CI 3 to 4, high-quality evidence), 8 mmHg
      (95% CI 7 to 9, high-quality evidence)/3 mmHg (95% CI 3 to 4, high-quality
      evidence) and 11 mmHg (95% CI 6 to 15, low-quality evidence)/5 mmHg (95% CI 3 to
      7, low-quality evidence), respectively.Direct comparison of doses did not show
      evidence of dose dependence for blood pressure-lowering for any of the other
      thiazides for which RCT data were available: bendrofluazide, chlorthalidone,
      cyclopenthiazide, metolazone or indapamide.In seven trials with a baseline blood
      pressure of 163/88 mmHg, chlorthalidone at doses of 12.5 mg to 75 mg/day reduced
      average blood pressure compared to placebo by 12.0 mmHg (95% CI 10 to 14, low
      quality evidence)/4 mmHg (95% CI 3 to 5, low-quality evidence).In 10 trials with
      a baseline blood pressure of 161/98 mmHg, indapamide at doses of 1.0 mg to 5.0
      mg/day reduced blood pressure compared to placebo by 9 mmHg (95% CI 7 to 10, low
      quality evidence)/4 (95% CI 3 to 5, low-quality evidence).We judged the maximal
      blood pressure-lowering effect of the different thiazides to be similar. Overall,
      thiazides reduced average blood pressure compared to placebo by 9 mmHg (95% CI 9
      to 10, high-quality evidence)/4 mmHg (95% CI 3 to 4, high-quality
      evidence).Thiazides as a class have a greater effect on systolic than on
      diastolic blood pressure, therefore thiazides lower pulse pressure by 4 mmHg to 6
      mmHg, an amount that is greater than the 3 mmHg seen with angiotensin-converting
      enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs) and renin
      inhibitors, and the 2 mmHg seen with non-selective beta-blockers. This is based
      on an informal indirect comparison of results observed in other Cochrane reviews
      on ACE inhibitors, ARBs and renin inhibitors compared with placebo, which used
      similar inclusion/exclusion criteria to the present review.Thiazides reduced
      potassium, increased uric acid and increased total cholesterol and triglycerides.
      These effects were dose-related and were least for hydrochlorothiazide.
      Chlorthalidone increased serum glucose but the evidence was unclear for other
      thiazides. There is a high risk of bias in the metabolic data. This review does
      not provide a good assessment of the adverse effects of these drugs because there
      was a high risk of bias in the reporting of withdrawals due to adverse effects.
      AUTHORS' CONCLUSIONS: This systematic review shows that hydrochlorothiazide has a
      dose-related blood pressure-lowering effect. The mean blood pressure-lowering
      effect over the dose range 6.25 mg, 12.5 mg, 25 mg and 50 mg/day is 4/2 mmHg, 6/3
      mmHg, 8/3 mmHg and 11/5 mmHg, respectively. For other thiazide drugs, the lowest
      doses studied lowered blood pressure maximally and higher doses did not lower it
      more. Due to the greater effect on systolic than on diastolic blood pressure,
      thiazides lower pulse pressure by 4 mmHg to 6 mmHg. This exceeds the mean 3 mmHg
      pulse pressure reduction achieved by ACE inhibitors, ARBs and renin inhibitors,
      and the 2 mmHg pulse pressure reduction with non-selective beta-blockers as shown
      in other Cochrane reviews, which compared these antihypertensive drug classes
      with placebo and used similar inclusion/exclusion criteria.Thiazides did not
      increase withdrawals due to adverse effects in these short-term trials but there
      is a high risk of bias for that outcome. Thiazides reduced potassium, increased
      uric acid and increased total cholesterol and triglycerides.

PMID- 24869751
TI  - Robotic giant hiatal hernia repair: 3 year prospective evaluation and review of
      the literature.
AB  - BACKGROUND: While conventional laparoscopic repair for giant hiatal hernias is
      considered difficult, robotic technology is likely to result in an improved
      postoperative course. METHODS: We prospectively analysed patients with giant
      hiatal hernias who underwent robotic repair during a 3 year period. Preoperative
      data, operative variables, complications, clinical outcomes and anatomical
      recurrence after 1 year were evaluated. RESULTS: Six patients with giant hiatal
      hernias underwent robotic repair using the Da Vinci surgical system. The mean
      operative time was 182 min. The mean hospital stay was 6 days. No patients
      required reoperation for disease recurrence, and all claimed the absence of
      postoperative symptoms. CONCLUSIONS: Robotic approaches can minimize surgical
      trauma in patients with giant hiatal hernias and result in favourable outcomes in
      terms of anatomical recurrence and quality of life. With the availability of the
      da Vinci System, all patients with giant hiatal hernias can be offered a
      minimally invasive surgical option.

PMID- 24869752
TI  - Diving medicine.
AB  - Exposure to the undersea environment has unique effects on normal physiology and
      can result in unique disorders that require an understanding of the effects of
      pressure and inert gas supersaturation on organ function and knowledge of the
      appropriate therapies, which can include recompression in a hyperbaric chamber.
      The effects of Boyle's law result in changes in volume of gas-containing spaces
      when exposed to the increased pressure underwater. These effects can cause middle
      ear and sinus injury and lung barotrauma due to lung overexpansion during ascent
      from depth. Disorders related to diving have unique presentations, and an
      understanding of the high-pressure environment is needed to properly diagnose and
      manage these disorders. Breathing compressed air underwater results in increased
      dissolved inert gas in tissues and organs. On ascent after a diving exposure, the
      dissolved gas can achieve a supersaturated state and can form gas bubbles in
      blood and tissues, with resulting tissue and organ damage. Decompression sickness
      can involve the musculoskeletal system, skin, inner ear, brain, and spinal cord,
      with characteristic signs and symptoms. Usual therapy is recompression in a
      hyperbaric chamber following well-established protocols. Many recreational diving
      candidates seek medical clearance for diving, and healthcare providers must be
      knowledgeable of the environmental exposure and its effects on physiologic
      function to properly assess individuals for fitness to dive. This review provides
      a basis for understanding the diving environment and its accompanying disorders
      and provides a basis for assessment of fitness for diving.

PMID- 24869753
TI  - Epidemiology of vaginal prolapse in mixed-age ewes in New Zealand.
AB  - AIMS: Identify environmental, animal, and management factors associated with risk
      of vaginal prolapse in ewes, to enable farmers and advisors to make pragmatic
      decisions based on empirical observations for control of the condition. METHODS:
      Two longitudinal studies conducted over 2 years to identify factors associated
      with incidence of prolapse in (i) cohorts of 200 individually identified mixed
      age (MA) ewes, and (ii) all MA ewes, on voluntarily participating sheep-breeding
      farms in Hawkes Bay (HB) and Southland regions of New Zealand. RESULTS: The
      overall annual incidences of prolapse on 113 farms in 2000 and 88 in 2001 were
      1.21 and 0.82 per 100 MA ewes, respectively, and 1.05 for both years combined. A
      total of 406 prolapses were recorded among 36,695 individually identified cohort
      ewes. Individual farm incidences for both years varied from 0-5.9 (mean=1.56,
      median=1.39) on Southland and 0-3.9 (mean=0.75, median=0.54) per 100 ewes on HB
      farms. The crude relative risk of a prolapse occurring in a MA ewe was 5.31 times
      higher for ewes carrying twins and 11.3 times higher for ewes carrying triplets,
      than single lambs. Flocks made up of predominantly pure or crossbred Perendale
      ewes appeared to be at lower risk than flocks with other breeds. Shearing in the
      3 months leading up to mating appeared to be protective, as was shearing in the
      second half of pregnancy. The risk was higher on farms with moderate to steep
      terrain than on farms with flat terrain. The identified risk factors in the
      individually identified cohorts were: access to salt and feeding of swedes in the
      latter part of pregnancy, moderate to steep lambing paddocks, multiple lambs
      detected at scanning, and weight gain between start of mating and scanning. The
      condition recurred in 2001 in six (35%) of 17 study ewes that had prolapsed
      during 2000. Culling policies for female offspring of affected ewes did not
      influence incidence at the farm level; nor did feeding hay or grain in late
      pregnancy. Furthermore, there was no association between incidence and body
      condition scores measured prior to and after mating, at scanning, or at time of
      set stocking. CLINICAL SIGNIFICANCE: Vaginal prolapse is an inevitable
      consequence of sheep reproduction and its incidence is expected to increase as
      reproductive rates increase. This study provides some firm leads as to the
      relative importance of risk factors and gives guidance for risk reduction, e.g.
      by identification and separate management of ewes carrying twins or triplets,
      using flat paddocks for lambing, and guarding against gain in weight between the
      start of mating and scanning.

PMID- 24869755
TI  - Multi-wall effects on the thermal transport properties of nanotube structures.
AB  - Understanding the role of inter-layer interactions in multi-walled carbon
      nanotubes is one of the challenges in the design of potential materials because
      of their large impact on the physical properties of carbon nanotubes. We focused
      on the thermal properties of double-walled carbon nanotubes (DWCNTs), which are
      promising materials due to their high durability and thermal efficiency. We
      investigated the thermal conductance of DWCNTs by using the nonequilibrium
      Green's function method, and found that the quadratic temperature dependence of
      the thermal conductance at low temperatures consisted of three regions with
      different tendencies. Based on analysis of the transmission coefficients and the
      distribution of the normal modes, the three nonuniform regions were attributed to
      the energy shifts of the normal modes at the low-energy region. We examined the
      mechanism of these energy shifts using the coupled vibration model with the
      parameters from our simulations, and elucidated the multi-wall effects on the
      thermal transport properties of the nanotube structures. The effects we found
      demonstrated the significance of tailoring thermal properties to obtain the
      desired applications.

PMID- 24869754
TI  - In vivo metabolic fingerprinting of neutral lipids with hyperspectral stimulated
      Raman scattering microscopy.
AB  - Metabolic fingerprinting provides valuable information on the physiopathological
      states of cells and tissues. Traditional imaging mass spectrometry and magnetic
      resonance imaging are unable to probe the spatial-temporal dynamics of
      metabolites at the subcellular level due to either lack of spatial resolution or
      inability to perform live cell imaging. Here we report a complementary metabolic
      imaging technique that is based on hyperspectral stimulated Raman scattering
      (hsSRS). We demonstrated the use of hsSRS imaging in quantifying two major
      neutral lipids: cholesteryl ester and triacylglycerol in cells and tissues. Our
      imaging results revealed previously unknown changes of lipid composition
      associated with obesity and steatohepatitis. We further used stable-isotope
      labeling to trace the metabolic dynamics of fatty acids in live cells and live
      Caenorhabditis elegans with hsSRS imaging. We found that unsaturated fatty acid
      has preferential uptake into lipid storage while saturated fatty acid exhibits
      toxicity in hepatic cells. Simultaneous metabolic fingerprinting of deuterium
      labeled saturated and unsaturated fatty acids in living C. elegans revealed that
      there is a lack of interaction between the two, unlike previously hypothesized.
      Our findings provide new approaches for metabolic tracing of neutral lipids and
      their precursors in living cells and organisms, and could potentially serve as a
      general approach for metabolic fingerprinting of other metabolites. 

PMID- 24869756
TI  - Expanding emergency department capacity: a multisite study.
AB  - OBJECTIVES: The aims of the present study were to identify predictors of
      admission and describe outcomes for patients who arrived via ambulance to three
      Australian public emergency departments (EDs), before and after the opening of 41
      additional ED beds within the area. METHODS: The present study was a
      retrospective comparative cohort study using deterministically linked health data
      collected between 3 September 2006 and 2 September 2008. Data included ambulance
      offload delay, time to see doctor, ED length of stay (LOS), admission
      requirement, access block, hospital LOS and in-hospital mortality. Logistic
      regression analysis was undertaken to identify predictors of hospital admission.
      RESULTS: Almost one-third of all 286037 ED presentations were via ambulance
      (n=79196) and 40.3% required admission. After increasing emergency capacity, the
      only outcome measure to improve was in-hospital mortality. Ambulance offload
      delay, time to see doctor, ED LOS, admission requirement, access block and
      hospital LOS did not improve. Strong predictors of admission before and after
      increased capacity included age >65 years, Australian Triage Scale (ATS) Category
      1-3, diagnoses of circulatory or respiratory conditions and ED LOS >4h. With
      additional capacity, the odds ratios for these predictors increased for age >65
      years and ED LOS >4h, and decreased for ATS category and ED diagnoses.
      CONCLUSIONS: Expanding ED capacity from 81 to 122 beds within a health service
      area impacted favourably on mortality outcomes, but not on time-related service
      outcomes such as ambulance offload time, time to see doctor and ED LOS. To
      improve all service outcomes, when altering (increasing or decreasing) ED bed
      numbers, the whole healthcare system needs to be considered.

PMID- 24869757
TI  - Screw insertion in osteoporotic bone: turn-of-the-nut and torque-based techniques
      provide similar resistance to bone plate slippage.
AB  - OBJECTIVES: To measure the resistance to plate slippage provided by a screw
      inserted to various torsional and rotational endpoints. MATERIALS AND METHODS: A
      7-hole, 3.5-mm narrow dynamic compression plate was affixed to an osteoporotic
      humeral shafts using screws inserted: (1) to 90 degrees after plate contact, (2)
      to 180 degrees after plate contact, (3) by the 1.4-N.m torque limit method, and
      (4) by the "2-fingers tight" method. The resistance of the plate to sliding
      against the bone was measured using a materials testing machine. We checked for
      an effect of screw insertion method on bone-plate slippage with a general
      linearized latent and mixed model, controlling for bone mineral density, sex, and
      specimen clustering. Significance was set at P < 0.05. RESULTS: The force
      required to slip the plate for 180 degrees of screw rotation was not
      significantly greater than that of the other insertion groups. CONCLUSIONS:
      Inserting screws 180 degrees after seating can be expected to yield plate contact
      to bone similar to that of the "2-fingers tight" standard.

PMID- 24869758
TI  - Potential infection risk from thyroid radiation protection.
AB  - OBJECTIVES: Thyroid shields that are worn for personal radiation protection in
      the operating room are often exposed above the sterile gown and are likely a
      bacterial source of wound infections. We would like to determine what bacteria
      may be present on the portion of the thyroid shield, which is facing the
      operative table. METHODS: Community thyroid shields were collected from around
      the operative rooms. The shields were then cultured on the side, which faces the
      patient and operative table. The shields where then cleaned with a readily
      available cleaner and again cultured to evaluate the reduction of bacterial load.
      Samples were cultured on nonselective media for 72 hours. RESULTS: Thirty-two
      total thyroid shields were cultured before and after cleaning. Before cleaning,
      81% of thyroid shields grew out at least 1 type of bacteria with 90% being
      coagulase negative staphylococcus. Postcleaning culturable contamination was
      reduced by 70% (P < 0.05). CONCLUSIONS: The thyroid shield that is often visible
      above the neckline is contaminated with strains of bacteria that are commonly
      implicated in postoperative infections. Cleaning the thyroid shield with readily
      available cleaners can significantly reduce the bacterial burden as detectable by
      culture. Based on the primary research question, this article is a basic science
      article.

PMID- 24869759
TI  - TCF4 silencing sensitizes the colon cancer cell line to oxaliplatin as a common
      chemotherapeutic drug.
AB  - Colon cancer is among the most prevalent cancers worldwide. Although the main
      modality of treatment is surgery, resistance to chemoradiotherapy raises
      concerns. Hence, we aimed to determine the effect of RNA-mediated silencing of
      tcf4, the downstream effector of the wnt signaling pathway, on the response of
      the SW480 cell line to oxaliplatin, a common chemotherapeutic drug. For this, two
      different silencing sequences against TCF4 mRNA were selected and cloned into
      pSilencer neo2.1. The SW480 cell line was stably transfected with the silencing
      constructs (namely p1396, p1874, and p silencer containing a scrambled sequence)
      and labeled SW1396, SW1874, and SW-Sc, respectively. Subsequently, the effect of
      oxaliplatin (from 0 to 11.25 MUmol/l) on these cells was studied using 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide proliferation assay.
      Suppression of tcf4 expression in stable transfected cells with p1396 and p1874
      was confirmed by quantitative reverse transcription-PCR and western blot
      analysis. Although oxaliplatin was not toxic to SW480 and SW-sc in the range
      tested, in SW1396 and SW1874 cells, a toxic effect was evident at 3.75 and 4.375
      MUmol/l. Also, SW1396 and SW1874 cells appeared to have a round shape in
      comparison with SW480 and SW-Sc cells. Only for SW1396, the number of apoptotic
      cells was significantly different before and after the addition of oxaliplatin
      (LC50 of oxaliplatin). The proliferating cells in SW480, SW1874, and SW-Sc
      increased after treatment with oxaliplatin; however, this was not observed in
      SW1396. Although silencing the tcf4 gene would confer sensitivity to oxaliplatin
      in SW1874 and especially SW1396, in SW480 and SW-Sc, the lethal effect of
      oxaliplatin was compensated by its effect in increasing the proliferation of
      cells. This sensitization effect may be because of different mechanisms including
      TCF4 motifs in the ABCB1 promoter or defects in nucleotide excision repair or
      double-strand break repair systems after tcf4 silencing. 

PMID- 24869760
TI  - Effects of oxymatrine on the apoptosis and proliferation of gallbladder cancer
      cells.
AB  - Gallbladder carcinoma is the most common malignancy of the biliary tract and is
      associated with a very poor outcome. The aim of the present study was to
      investigate the effects of oxymatrine (OM) on gallbladder cancer cells and the
      possible mechanism of its effects. The effects of OM on the proliferation of
      gallbladder cancer cells (GBC-SD and SGC-996) were investigated using cell
      counting kit-8 and colony formation assays. Annexin V/propidium iodide double
      staining was performed to investigate whether OM could induce apoptosis in
      gallbladder cancer cells. The mitochondrial membrane potential (DeltaPsim) and
      expression of apoptosis-associated proteins were evaluated to identify a
      mechanism for the effects of OM. In addition, the RNA expression of relevant
      genes was measured by qRT-PCR using the SYBR Green method. Finally, a
      subcutaneous implantation model was used to verify the effects of OM on tumor
      growth in vivo. We found that OM inhibited the proliferation of gallbladder
      cancer cells. In addition, Annexin V/propidium iodide double staining showed that
      OM induced apoptosis after 48 h and the DeltaPsim decreased in a dose-dependent
      manner after OM treatment. Moreover, the activation of caspase-3 and Bax and
      downregulation of Bcl-2 and nuclear factor kappaB were observed in OM-treated
      cells. Finally, OM potently inhibited in-vivo tumor growth following subcutaneous
      inoculation of SGC-996 cells in nude mice. In conclusion, OM treatment reduced
      proliferation and induced apoptosis in gallbladder cancer cells, which suggests
      that this drug may serve as a novel candidate for adjuvant treatment in patients
      with gallbladder cancer. 

PMID- 24869761
TI  - A systematic review of raltitrexed-based first-line chemotherapy in advanced
      colorectal cancer.
AB  - Raltitrexed is a thymidylate synthase inhibitor belonging to the antimetabolite
      class of cytotoxic drugs. It is also effective in colorectal cancer (CRC) both as
      a single agent and in combination with other drugs, in particular in those
      patients with cardiologic risk factors or previous cardiotoxicity. The efficacy
      of first-line raltitrexed-based chemotherapy containing oxaliplatin (TOMOX) and
      irinotecan (TOMIRI) was investigated in this systematic review. Studies that
      enrolled advanced CRC patients for first-line therapy with TOMOX/TOMIRI
      combinations were identified using electronic databases (Pubmed, SCOPUS, Web of
      Science, EMBASE, and the Cochrane Library). A systematic analysis was carried out
      using Comprehensive Meta Analysis (version 2.2.064) software to calculate the
      pooled response rate and 95% confidence limits. The median pooled overall
      survival and progression-free survival were also calculated. Results for TOMOX
      and TOMIRI studies were compared using the two-sided Student's t-test. We tested
      for significant heterogeneity using Cochran's chi-test and I index. Twelve
      studies published between 2001 and 2012 were eligible for this analysis and a
      total of 735 patients were enrolled in these studies. The overall response rate
      was 40% (95% confidence interval 34-46%): 43.9% for TOMOX and 34.1% for TOMIRI
      arms. The weighted median overall survival and progression-free survival times
      were 14.6 and 6.7 months, respectively. Neutropenia and liver toxicity were more
      frequent with TOMOX, whereas neutropenia and diarrhea were more frequent with
      TOMIRI. However, compared with historical FOLFOX and FOLFIRI trials, raltitrexed
      based doublets are associated with less neutropenia and gastrointestinal toxicity
      and uncommon cardiotoxicity. TOMOX and TOMIRI doublets are active as first-line
      chemotherapy for advanced CRC and seem useful in particular when the use of 5
      fluorouracil is contraindicated for cardiac comorbidity. 

PMID- 24869762
TI  - Factors contributing to adverse perioperative events in adults with congenital
      heart disease: a structured analysis of cases from the closed claims project.
AB  - OBJECTIVE: Prior investigations have suggested that the rapidly growing
      population of adults with congenital heart disease is at increased risk of
      perioperative morbidity and mortality, but information is limited on the nature
      of those perioperative factors that may relate to adverse outcomes. We sought to
      use a national claims database to describe the contribution of perioperative
      factors to adverse outcomes and compare contributing factors in cardiac vs.
      noncardiac operations. DESIGN: The study is a retrospective in-depth structured
      analysis of cases from the Anesthesia Closed Claims Project database. SETTING: We
      examined the largest national anesthesia malpractice claims database. PATIENTS:
      We included all claims cases involving adult patients with congenital heart
      disease (CHD). INTERVENTIONS: Patients in this retrospective analysis were
      classified by type of surgery (cardiac or noncardiac). OUTCOME MEASURES:
      Perioperative factors contributing to an adverse event were assessed by an expert
      panel of cardiac anesthesiologists. RESULTS: Of 21 confirmed cases, 11 (52%)
      involved cardiac procedures and 10 (48%) noncardiac procedures. The most common
      factors contributing to the adverse event in cardiac cases were surgical
      technique (73% of cases) and intraoperative anesthetic care (55%), whereas in
      noncardiac cases, postoperative monitoring/care (50%), CHD (50%) and preoperative
      assessment or optimization (40%) were most common. The factors contributing to
      the patient injury differed similarly: in cardiac cases, the most common factors
      were intraoperative anesthetic care (55%) and surgical technique (45%) compared
      with postoperative monitoring/care (50%) and CHD (50%) in noncardiac cases.
      CONCLUSIONS: Within the limitations of a small number of events in a claims-based
      database, this study offers advantages of being a national, structured analysis
      of real cases to provide detailed information on phenomena that are otherwise
      abstract and hypothesized by expert opinion. These results should help affirm the
      role of anesthesiologists in acquiring and executing expertise as consultants in
      perioperative medicine for adults with congenital heart disease patients.

PMID- 24869763
TI  - The risk of recurrent IgA nephropathy in a steroid-free protocol and other
      modifying immunosuppression.
AB  - Recurrent glomerulonephritis is an important cause of kidney allograft failure.
      The effect of immunosuppression on recurrent IgA nephropathy (IgAN) is unclear.
      We analyzed the impact of steroids and other immunosuppression on the risk of
      recurrent IgAN post-kidney transplantation. Between June 1989 and November 2008,
      3311 kidney transplants were performed at our center. IgAN was the primary
      disease in 124 patients; of these, 75 (60.5%) patients received steroid-based
      immunosuppression (15 undergoing late steroid withdrawal), and 49 (39.5%) were
      maintained on steroid-free immunosuppression. Recurrent IgAN was diagnosed in 27
      of 124 (22%) patients in clinically indicated kidney allograft biopsies over a
      median follow-up of 6.86 +/- 5.4 yr. On cox proportional hazards model
      multivariate analysis, the hazard risk (HR) of IgAN recurrence was significantly
      higher in patients managed with steroid-free (HR 8.59: 3.03, 24.38, p < 0.001)
      and sirolimus-based (HR = 3.00:1.16, 7.75, p = 0.024) immunosuppression without
      antilymphocyte globulin induction (HR = 4.5: 1.77, 11.73, p = 0.002).
      Mycophenolate use was associated with a lower risk (HR = 0.42: 0.19, 0.95, p =
      0.036), whereas cyclosporine did not have a significant impact on the risk of
      IgAN recurrence (p = 0.61). These results warrant future prospective studies
      regarding the role of steroids and other immunosuppression drugs in reducing
      recurrence of IgAN and other glomerulonephritis post-transplant.

PMID- 24869765
TI  - Dammarane-type triterpenoids as 11beta-HSD1 inhibitors from Homonoia riparia.
AB  - An exploration for 11beta-HSD1 inhibitors from Homonoia riparia returned eight
      new dammarane-type triterpenoids, horipenoids A-H (1-8), and a known oleanane
      type triterpenoid (9). Their structures were elucidated on the basis of
      comprehensive analysis of spectroscopic data, and the absolute configuration of
      horipenoid E (5) was established by single crystal X-ray crystallography.
      Compounds 1-4 represent a rare class of octanortriterpenoids. Horipenoids C (3)
      and E (5) showed potent inhibition against mouse 11beta-HSD1 with IC50 values of
      0.810 +/- 0.058 and 0.898 +/- 0.215 MUM, respectively.

PMID- 24869766
TI  - Autonomous motion and temperature-controlled drug delivery of Mg/Pt-poly(N
      isopropylacrylamide) Janus micromotors driven by simulated body fluid and blood
      plasma.
AB  - In this work, we have demonstrated the autonomous motion of biologically-friendly
      Mg/Pt-Poly(N-isopropylacrylamide) (PNIPAM) Janus micromotors in simulated body
      fluids (SBF) or blood plasma without any other additives. The pit corrosion of
      chloride anions and the buffering effect of SBF or blood plasma in removing the
      Mg(OH)2 passivation layer play major roles for accelerating Mg-H2O reaction to
      produce hydrogen propulsion for the micromotors. Furthermore, the Mg/Pt-PNIPAM
      Janus micromotors can effectively uptake, transport, and temperature-control
      release drug molecules by taking advantage of the partial surface-attached
      thermoresponsive PNIPAM hydrogel layers. The PNIPAM hydrogel layers on the
      micromotors can be easily replaced with other responsive polymers or antibodies
      by the surface modification strategy, suggesting that the as-proposed micromotors
      also hold a promising potential for separation and detection of heavy metal ions,
      toxicants, or proteins. 

PMID- 24869767
TI  - Effects of maternal ageing on ICSI outcomes and embryo development in relation to
      oocytes morphological characteristics of birefringent structures.
AB  - The aim of this study was to determine the morphological characteristics of the
      older reproductive aged women's oocytes and to reveal the influence of these
      characteristics on intra-cytoplasmic sperm injection (ICSI) outcomes. The oocytes
      of women older than 35 years of age were evaluated retrospectively. Non-invasive
      polarization microscopy (PolScope) examinations of mature oocytes were performed
      by measurement of meiotic spindles' length, area and retardance and zona
      pellucida thickness and retardance. Fertilization and conception competence and
      the correlation with the birefringent structures were assessed. Two hundred and
      thirteen mature oocytes from 54 women were evaluated with a PolScope. Length of
      the meiotic spindle was shown to be related to fertilization success of women
      with advanced maternal age. In conclusion, the PolScope is a useful device used
      to identify the oocyte quality. Quantitative measurements of meiotic spindle
      parameters may be valuable for the selection of high-quality oocytes that have
      the potential for embryo development in the in vitro fertilization (IVF)
      laboratory of women older than 35 years of age who are mostly poor responders. 

PMID- 24869768
TI  - Using model-based screening to help discover unknown environmental contaminants.
AB  - Of the tens of thousands of chemicals in use, only a small fraction have been
      analyzed in environmental samples. To effectively identify environmental
      contaminants, methods to prioritize chemicals for analytical method development
      are required. We used a high-throughput model of chemical emissions, fate, and
      bioaccumulation to identify chemicals likely to have high concentrations in
      specific environmental media, and we prioritized these for target analysis. This
      model-based screening was applied to 215 organosilicon chemicals culled from
      industrial chemical production statistics. The model-based screening prioritized
      several recognized organosilicon contaminants and generated hypotheses leading to
      the selection of three chemicals that have not previously been identified as
      potential environmental contaminants for target analysis. Trace analytical
      methods were developed, and the chemicals were analyzed in air, sewage sludge,
      and sediment. All three substances were found to be environmental contaminants.
      Phenyl-tris(trimethylsiloxy)silane was present in all samples analyzed, with
      concentrations of ~50 pg m(-3) in Stockholm air and ~0.5 ng g(-1) dw in sediment
      from the Stockholm archipelago. Tris(trifluoropropyl)trimethyl-cyclotrisiloxane
      and tetrakis(trifluoropropyl)tetramethyl-cyclotetrasiloxane were found in
      sediments from Lake Mjosa at ~1 ng g(-1) dw. The discovery of three novel
      environmental contaminants shows that models can be useful for prioritizing
      chemicals for exploratory assessment. 

PMID- 24869770
TI  - Syntheses, structures and photocatalytic properties of five new praseodymium
      antimony oxochlorides: from discrete clusters to 3D inorganic-organic hybrid
      racemic compounds.
AB  - Five novel praseodymium-antimony oxochloride (Pr-Sb-O-Cl) cluster-based
      compounds, namely (2-MepyH)2[Fe(1,10-phen)3]2[Pr4Sb12O18Cl14.6(OH)2.4(Hsal)].H2O
      (1), (2-MepyH)2[Fe(1,10
      phen)3]4{[Pr4Sb12O18Cl13.5(OH)0.5](bcpb)2[Pr4Sb12O18Cl13.5(OH)0.5]}.42H2O (2), (3
      MepyH)2[Fe(1,10-phen)3]{[Pr4Sb12O18Cl13(H2O)2](bcpb)}.2(3-Mepy).3H2O (3),
      [Fe(1,10-phen)3]2{[Pr4Sb12O18Cl10(H2O)2](bcpb)2}.3(3-Mepy).13H2O (4), and (2
      MepyH)6[Fe(1,10
      phen)3]10{[Pr4Sb12O18Cl13(OH)2]2[Pr4Sb12O18Cl9][Pr4Sb12O18Cl9(OH)2]2(Hpdc)10(pdc)
      }.110H2O (5) (2-Mepy = 2-methylpyridine, 3-Mepy = 3-methylpyridine, 1,10-phen =
      1,10-phenanthroline, H2sal = salicylic acid, H3bcpb = 3,5-bis(4
      carboxyphenoxy)benzoic acid, H3pdc = 3,5-pyrazoledicarboxylic acid) have been
      solvothermally synthesized and structurally characterized. Compound 1 is the
      first zero-dimensional (0D) Pr-Sb-O-Cl cluster decorated by an organic ligand.
      Compounds 2-4 are constructed from the same H3bcpb ligands but adopt different
      structures: 2 represents a rare example of a one-dimensional (1D) nanotubular
      structure based on high-nuclearity clusters; 3 exhibits a two-dimensional (2D)
      mono-layered structure, in which left-handed and right-handed helical chains are
      alternately arranged, while 4 features a double-layered structure with an
      unprecedented (3,3,6)-connected 3-nodal topological net. Compound 5 is a unique
      three-dimensional (3D) 2-fold interpenetrating racemic compound, simultaneously
      containing three kinds of Pr-Sb-O-Cl-pdc clusters. UV-light photocatalytic H2
      evolution activity was observed for compound 3 with Pt as a co-catalyst and MeOH
      as a sacrificial electron donor. In addition, the magnetic properties of
      compounds 1 and 5 are also studied. 

PMID- 24869769
TI  - Selenium speciation in malt, wort, and beer made from selenium-biofortified two
      rowed barley grain.
AB  - Selenium (Se) biofortification of barley is a suitable strategy to increase the
      Se concentration in grain. In the present paper, the suitability of this Se
      biofortified grain for making Se-enriched beer is analyzed. The aim of the
      present study was to evaluate the effect of different Se fertilizer doses (0, 10,
      and 20 g of Se ha(-1)) and forms (sodium selenate or sodium selenite) on the Se
      loss during the malting and brewing processes and Se speciation in grain, malt,
      wort, and beer. Samples were analyzed using inductively coupled plasma-mass
      spectrometry (ICP-MS) and high-performance liquid chromatography (HPLC)-ICP-MS
      for total Se and speciation. Mashing-lautering was the process with the greatest
      Se loss (83.8%). After malting and brewing, only 7.3% of the initial Se was
      retained in beer, mainly in selenite form. Even so, the fertilizer application of
      sodium selenate at 20 g ha(-1) increased the total Se concentration almost 6-fold
      in the final beer in comparison to the use of grain derived from unfertilized
      barley. The present paper provides evidence that the use of Se-biofortified
      barley grain as a raw material to produce Se-enriched beer is possible, and the
      results are comparable to other methods in terms of efficiency. 

PMID- 24869771
TI  - Zinc-mediated CH-activation of tetrahydrofuran under mild conditions for the
      regioselective addition to aryl-propiolates.
AB  - The CH-activation of THF is realized in a zinc-mediated process using a
      dibromocyclopropane as a crucial additive. The highly regioselective addition to
      aryl-substituted propiolates as well as the regio- and stereoselective addition
      to diynes are described. 

PMID- 24869774
TI  - N-heterocyclic carbene-palladium(II)-1-methylimidazole complex-catalyzed direct C
      H bond arylation of (benz)imidazoles with aryl chlorides.
AB  - (Benz)imidazoles can be efficiently functionalized by (hetero)aryl chlorides via
      direct C-H bond arylation in the presence of a well-defined NHC-Pd(II)-Im
      complex. Under the optimal conditions, various activated, unactivated, and
      deactivated (hetero)aryl chlorides were successfully applied as the arylating
      reagents to achieve the 2-(hetero)aryl (benz)imidazoles in acceptable to high
      yields, giving a facile and alternative methodology for the direct C-H bond
      arylation of (benz)imidazoles. 

PMID- 24869775
TI  - Gas-phase generation and matrix isolation of the methylsulfonyl radical CH3SO2
      from allylmethylsulfone.
AB  - The atmospherically highly relevant methylsulfonyl radical (CH3SO2(*)) was
      generated by high-vacuum flash pyrolysis (HVFP) of allylmethylsulfone and
      isolated in an argon matrix at 10 K; the allyl radical formed as the cofragment.
      Upon thermolysis, the methylsulfonyl radical undergoes partial decomposition,
      leading to substantial amounts of sulfur dioxide in the matrix. The title
      compound was characterized through the assignment of eight fundamental IR bands
      of its CD3 and (13)CH3 isotopologues and the excellent agreement with the B3LYP/6
      311+G(3df,3pd) computed harmonic vibrational frequencies. The two most intense
      absorptions were found at 1267.1 and 1067.6 cm(-1). In extension of this study S
      methyl methanethiosulfonate was found to be another suitable, although less
      efficient, precursor for the gas-phase generation of the methylsulfonyl radical. 

PMID- 24869777
TI  - Sorting particles with nanoscale thermophoretic devices: how efficient is it?
AB  - We investigate particle separation driven by thermal gradients across solid state
      nanopores using a combined molecular dynamics simulation, non-equilibrium
      thermodynamics theory and a kinetic model approach. The thermophoretic device, a
      thermal nanopump, exploits thermal gradients to sort particles of different mass,
      which accumulate preferentially in hot or cold reservoirs. We show that the large
      amount of energy dissipated by the thermal nanopump during the transport process
      leads in general to very low efficiencies, 0.01-0.15%. We find that the nanopump
      thermal conductivity and structure plays a crucial role in determining the
      efficiency and a route to enhance it. Doubling the pore radius, from 0.5-1 nm
      radius, leads to a large increase in the mass diffusion and to a 20 fold increase
      in the efficiency. Addition of nanoscale defects, without modification of the
      nanopore structure, leads to a large reduction of the nanopump thermal
      conductivity and to a large enhancement of the thermodynamic efficiency. We find
      that nanopumps with nanoscale defects are >3 times more efficient than those
      without defects. Finally, we identify the microscopic variables responsible for
      the enhancement of thermally induced transport across nanopores and discuss
      strategies to tune these variable in order to regulate transport efficiency. 

PMID- 24869776
TI  - Highly stable photoresponsive complex framework formation involves unusual
      selective hydrogenation of a pyridine derivative.
AB  - A unique hydrothermal selective hydrogenation process is carried out effectively
      in a simple and friendly way without adding any precious metal catalysts and
      hydrogen gas from outside. The self-assembly of the hydrogenated product 3-(4
      (pyridin-4-yl)piperidin-1-yl) benzoate (PYPDB) with the zinc ion produces a
      highly stable photoactive complex Zn(PYPDB)2 displaying interesting long range
      electron transfer behavior in the conjugated ring system. 

PMID- 24869773
TI  - Lysine methylation is an endogenous post-translational modification of tau
      protein in human brain and a modulator of aggregation propensity.
AB  - In Alzheimer's disease, the microtubule-associated protein tau dissociates from
      the neuronal cytoskeleton and aggregates to form cytoplasmic inclusions. Although
      hyperphosphorylation of tau serine and threonine residues is an established
      trigger of tau misfunction and aggregation, tau modifications extend to lysine
      residues as well, raising the possibility that different modification signatures
      depress or promote aggregation propensity depending on site occupancy. To
      identify lysine residue modifications associated with normal tau function,
      soluble tau proteins isolated from four cognitively normal human brains were
      characterized by MS methods. The major detectable lysine modification was found
      to be methylation, which appeared in the form of mono- and di-methyl lysine
      residues distributed among at least 11 sites. Unlike tau phosphorylation sites,
      the frequency of lysine methylation was highest in the microtubule-binding repeat
      region that mediates both microtubule binding and homotypic interactions. When
      purified recombinant human tau was modified in vitro through reductive
      methylation, its ability to promote tubulin polymerization was retained, whereas
      its aggregation propensity was greatly attenuated at both nucleation and
      extension steps. These data establish lysine methylation as part of the normal
      tau post-translational modification signature in human brain, and suggest that it
      can function in part to protect against pathological tau aggregation.

PMID- 24869778
TI  - Significance of beta-dehydrogenation in ethanol electro-oxidation on platinum
      doped with Ru, Rh, Pd, Os and Ir.
AB  - In the exploration of highly efficient direct ethanol fuel cells (DEFCs), how to
      promote the CO2 selectivity is a key issue which remains to be solved. Some
      advances have been made, for example, using bimetallic electrocatalysts, Rh has
      been found to be an efficient additive to platinum to obtain high CO2 selectivity
      experimentally. In this work, the mechanism of ethanol electrooxidation is
      investigated using the first principles method. It is found that CH3CHOH* is the
      key intermediate during ethanol electrooxidation and the activity of beta
      dehydrogenation is the rate determining factor that affects the completeness of
      ethanol oxidation. In addition, a series of transition metals (Ru, Rh, Pd, Os and
      Ir) are alloyed on the top layer of Pt(111) in order to analyze their effects.
      The elementary steps, alpha-, beta-C-H bond and C-C bond dissociations, are
      calculated on these bimetallic M/Pt(111) surfaces and the formation potential of
      OH* from water dissociation is also calculated. We find that the active metals
      increase the activity of beta-dehydrogenation but lower the OH* formation
      potential resulting in the active site being blocked. By considering both beta
      dehydrogenation and OH* formation, Ru, Os and Ir are identified to be unsuitable
      for the promotion of CO2 selectivity and only Rh is able to increase the
      selectivity of CO2 in DEFCs. 

PMID- 24869779
TI  - Cluster solvation models of carbon nanostructures: extension to fullerenes,
      tubes, and buds.
AB  - Carbon nanobud (CNB), a hybrid material consisting of single-wall C-nanotubes
      (CNTs) (SWNTs) with covalently attached fullerenes, in cluster form is discussed
      in organic solvents. Theories are developed based on bundlet and droplet models
      describing size-distribution functions. Phenomena present a unified explanation
      in bundlet model in which free energy of CNBs involved in cluster is combined
      from two parts: a volume one proportional to the number of molecules n in
      aggregate and a surface one, to n(1/2). Bundlet model enables describing
      distribution function of CNB clusters by size. From purely geometrical
      considerations bundlet (SWNT/CNB) and droplet (fullerene) models predict
      dissimilar behaviors. Interaction-energy parameters of CNBs are taken from C60. A
      C60/SWNT in-between behavior is expected; however, properties of CNBs result
      closer to SWNTs. Smaller CNB clusters result less stable but greater ones are
      more stable than SWNT bundles. The solubility decays with temperature result
      smaller for SWNT/CNB than C60 in agreement with lower number of units in
      aggregates. Discrepancy between the experimental data of heat of solution of
      fullerenes and CNT/CNBs is ascribed to sharp concentration dependence of heat of
      solution. Diffusion coefficient decays with temperature and results greater for
      CNB than SWNT or C60. Clusters (C60)13 and SWNT/CNB7 are representative of
      droplet and bundlet models.

PMID- 24869780
TI  - Effect of explicit water molecules on ligand-binding affinities calculated with
      the MM/GBSA approach.
AB  - We tested different approaches to including the effect of binding-site water
      molecules for ligand-binding affinities within the MM/GBSA approach (molecular
      mechanics combined with generalised Born and surface-area solvation). As a test
      case, we studied the binding of nine phenol analogues to ferritin. The effect of
      water molecules mediating the interaction between the receptor and the ligand can
      be studied by considering a few water molecules as a part of the receptor. We
      extended previous methods by allowing for a variable number of water molecules in
      the binding site. The effect of displaced water molecules can also be considered
      within the MM/GBSA philosophy by calculating the affinities of binding-site water
      molecules, both before and after binding of the ligand. To obtain proper
      energies, both the water molecules and the ligand need then to be converted to
      non-interacting ghost molecules and a single-average approach (i.e., the same
      structures are used for bound and unbound states) based on the simulations of
      both the complex and the free receptor can be used to improve the precision. The
      only problem is to estimate the free energy of an unbound water molecule. With an
      experimental estimate of this parameter, promising results were obtained for our
      test case. 

PMID- 24869781
TI  - Structural/electronic properties and reaction energies of a series of mono- and
      bis-uranyl dihalides equatorially coordinated by N/O ligands.
AB  - Monometallic (UO2)(X)2(L)3 (L = pyridine (py), X = F (1), Cl (2), Br (3) and I
      (4); L = tetrahydrofuran (thf), X = Cl (5); L = pyrrole (pl), X = Cl (6)) as well
      as bimetallic [(UO2)(MU2-X)(X)(L)2]2 (L = py, X = F (7), Cl (8), Br (9) and I
      (10); L = thf, X = Cl (11); L = pl, X = Cl (12); MU 2 = doubly bridged) were
      examined using relativistic density functional theory. With changing from F, Cl,
      Br to I irregardless of in mono- or bis-uranyl complexes, bond lengths of U = O
      were calculated to be decreasing, resulting from strengthening of axial U = O
      bonds while weakening equatorial X -> U coordination. This is further evidenced
      by calculated bond orders of U = O and stretching vibrational frequencies. A
      similar situation was is found in 2, 5 and 6 as well as in 8, 11 and 12, where
      N/O ligands are varied but the chlorine atoms are retained. The present study
      reveals that all these complexes have U(f)-character low-lying unoccupied
      orbitals, and their pi*(U = O) antibonds are located on higher-energy orbitals.
      Complex 1 was calculated to show sigma(U = O) bonding character for HOMO, and
      pyridine-character for other occupied orbitals; the fluorine ligand occurs in a
      relatively low-energy region. In contrast, the pi(p) characters of heavier
      halogen atoms significantly contribute to most frontier molecular orbitals of 2,
      3 and 4. Unlike this electronic feature of 2, complexes 5 and 6 exhibit mainly
      thf and pyrrole characters, respectively, for their high-lying occupied orbitals.
      Electronic structures of bisuranyl complexes 7-12, albeit a little more
      complicated, are revealed to be similar to those of the corresponding monouranyl
      complexes. Finally, energies of formation reactions of the above complexes were
      calculated and compared with available experimental results. 

PMID- 24869782
TI  - Theoretical prediction of the mechanisms for defect healing or oxygen doping in a
      hexagonal boron nitride (h-BN) sheet with nitrogen vacancies by NO2 molecules.
AB  - Healing defects in hexagonal boron nitride (h-BN sheet) or doping it with oxygen
      can modify or restore its physical properties, which would increase its range of
      potential applications. Thus, it is very important to find an efficient method of
      healing or a BN sheet or doping it with oxygen. In this work, using density
      functional theory (DFT) calculations, we identified a mechanism for healing h-BN
      sheets with nitrogen vacancies (VN) or doping BN sheets with oxygen using NO2
      molecules. The results indicate that such reactions involve three steps: (1) the
      chemisorption of NO2, (2) the incorporation of the N or O atom of NO2 into the
      defective h-BN sheet, and (3) the removal of the adsorbed O atom or NO molecule.
      We found that the proposed mechanism is theoretically possible and has the
      following advantages. First, the barrier is about 0.60 eV for the formation of
      the O-doped h-BN sheet. For the healing process, because the energy released
      during NO2 chemisorption (-4.94 eV) completely offsets the subsequent barrier
      (1.17 eV), a perfect h-BN sheet can easily be achieved by using NO2 and an h-BN
      sheet with VB defects as reactants. Second, no catalyst is needed, and thus there
      is no need for a purification step to remove the catalyst. Third, NO2, a toxic
      gas, can be used as a reactant and will then be reduced to O2 or NO. Fourth, NO2
      shows high selectivity for vacancy defect sites. Our findings show that this is
      an effective theoretical method of synthesizing O-doped h-BN sheets or of healing
      defective h-BN sheets, which should prove useful in the design of h-BN sheet
      based devices. 

PMID- 24869784
TI  - Total synthesis of indole alkaloid (+/-)-subincanadine E.
AB  - The first total synthesis of indole alkaloid (+/-)-subincanadine E has been
      accomplished. Ni(COD)2-mediated intramolecular Michael addition and zinc-mediated
      fragmentation reaction served as two key transformations. 

PMID- 24869783
TI  - Exposure to 1800 MHz radiofrequency radiation impairs neurite outgrowth of
      embryonic neural stem cells.
AB  - A radiofrequency electromagnetic field (RF-EMF) of 1800 MHz is widely used in
      mobile communications. However, the effects of RF-EMFs on cell biology are
      unclear. Embryonic neural stem cells (eNSCs) play a critical role in brain
      development. Thus, detecting the effects of RF-EMF on eNSCs is important for
      exploring the effects of RF-EMF on brain development. Here, we exposed eNSCs to
      1800 MHz RF-EMF at specific absorption rate (SAR) values of 1, 2, and 4 W/kg for
      1, 2, and 3 days. We found that 1800 MHz RF-EMF exposure did not influence eNSC
      apoptosis, proliferation, cell cycle or the mRNA expressions of related genes. RF
      EMF exposure also did not alter the ratio of eNSC differentiated neurons and
      astrocytes. However, neurite outgrowth of eNSC differentiated neurons was
      inhibited after 4 W/kg RF-EMF exposure for 3 days. Additionally, the mRNA and
      protein expression of the proneural genes Ngn1 and NeuroD, which are crucial for
      neurite outgrowth, were decreased after RF-EMF exposure. The expression of their
      inhibitor Hes1 was upregulated by RF-EMF exposure. These results together
      suggested that 1800 MHz RF-EMF exposure impairs neurite outgrowth of eNSCs. More
      attention should be given to the potential adverse effects of RF-EMF exposure on
      brain development.

PMID- 24869786
TI  - Multiplex fluorophore systems on DNA with new diverse fluorescence properties and
      ability to sense the hybridization dynamics.
AB  - We developed a multiplexed fluorophore system on a DNA scaffold (MFD) that
      produced new and diverse fluorescence properties depending on the mixing pattern
      and sequence that could not be obtained from each monomer fluorophore. Our
      approach for producing new fluorescence properties is relatively facile: simply
      mixing fluorophores on a DNA scaffold provides large variations in the color and
      intensity using only one excitation wavelength with high "Stokes shifts" (~190
      nm). Furthermore these special fluorescence properties could be controlled by the
      hybridization pattern and were therefore dependent on the structural changes in
      DNA.

PMID- 24869785
TI  - Has work replaced home as a haven? Re-examining Arlie Hochschild's Time Bind
      proposition with objective stress data.
AB  - Using innovative data with objective and subjective measures of stress collected
      from 122 employed men and women, this paper tests the thesis of the Time Bind by
      asking whether people report lower stress levels at work than at home. The study
      finds consistent support for the Time Bind hypothesis when examining objective
      stress data: when participants were at work they had lower values of the stress
      hormone cortisol than when they were at home. Two variables moderated this
      association - income and children at home - such that the work as haven effect
      was stronger for those with lower incomes and no children living at home.
      Participants also, however, consistently reported higher subjective stress levels
      on work days than on non-work days, which is in direct contrast to the Time Bind
      hypothesis. Although our overall findings support Hochschild's hypothesis that
      stress levels are lower at work, it appears that combining work and home
      increases people's subjective experience of daily stress. 

PMID- 24869787
TI  - Limited role for histopathological examination of re-excision specimens of
      completely excised melanomas.
AB  - The Dutch melanoma guideline advises to examine one central block of the re
      excision scar in case of a complete primary excision. To increase the evidence
      for this recommendation, we re-evaluated how often residual melanoma was found in
      re-excision specimens of a large series of completely excised melanomas. Of 1,209
      Dutch melanoma cases, pathology reports of primary excisions were reviewed.
      Presence of melanoma in the margins was scored. All melanomas with a complete
      primary excision were included and pathology reports of re-excisions were
      reviewed. Presence of residual melanoma in the re-excision specimen and the
      number of blocks were scored. Slides of re-excision specimens containing residual
      melanoma were reviewed. Eventually, in four out of 812 melanomas (0.5 %) with a
      complete primary excision, residual melanoma was found in the re-excision
      specimen. The free margins of the primary melanomas in these cases ranged from
      0.5-3.5 mm. In one case, the margin for melanoma in situ was 0.2 mm. In <1 % of
      initially completely excised melanomas, residual melanoma was found in the re
      excision specimen. Histopathological examination of these re-excision specimens
      may not be cost-efficient. Our findings even imply that a re-excision could
      safely be omitted in selected cases of completely excised melanomas.

PMID- 24869788
TI  - Inter-rater agreement in the characterization of cystic renal lesions on contrast
      enhanced MRI.
AB  - PURPOSE: To evaluate inter-observer agreement of MRI features and classification
      of cystic renal masses among radiologist and radiology trainees. METHODS: Four
      readers (two radiologists and two radiology trainees) retrospectively reviewed
      100 cystic renal lesions on gadolinium enhanced MRI and assigned each a Bosniak
      classification (1, 2, 2F, 3, and 4). Lesions were also assessed on their
      individual features including size, presence of nodules, septations, and
      enhancement. Readers ranked their level of confidence regarding Bosniak
      classifications. Inter-observer variability of lesion classification and features
      was evaluated between raters at both radiologist and radiology trainee levels as
      well as the level of agreement of all four readers using weighted Kappa and
      intraclass correlation coefficient (ICC). RESULTS: One hundred cystic renal
      lesions were evaluated. There was moderate and substantial classification
      agreement between trainees and radiologists (ICC 0.59 and 0.63, respectively).
      There was substantial classification agreement among all four readers (0.66) with
      the lowest level of agreement for Bosniak 2F lesions (ICC 0.14). There was
      moderate-substantial agreement for the presence of nodular component, septations,
      and enhancement. Staff demonstrated highest agreement when assessing for nodular
      components (0.73). Agreement for the presence of enhancement was lowest (0.37 and
      0.42 for radiologists and trainees, respectively). Reported confidence was higher
      among radiologists compared with trainees. CONCLUSION: There is substantial
      overall inter-observer agreement in the MRI classification of cystic renal
      lesions. Confidence increases as rater experience increases.

PMID- 24869789
TI  - Correlation of CT patterns of primary intrahepatic cholangiocarcinoma at the time
      of presentation with the metastatic spread and clinical outcomes: retrospective
      study of 92 patients.
AB  - OBJECTIVE: To study the CT appearance and histopathology of mass-forming
      intrahepatic cholangiocarcinoma (IHCC) at presentation and correlate these
      features with metastatic disease and patient survival. MATERIALS AND METHODS: In
      this IRB-approved, HIPAA compliant retrospective study, we reviewed pathology
      database of 459 patients with cholangiocarcinoma seen from 2004 through 2013 to
      identify 92 patients with IHCC (48 women, 44 men, mean age 61 years) who had CT
      scans of primary tumor available for review. All baseline and follow-up CT's were
      reviewed by two radiologists in consensus to record imaging characteristics and
      metastatic patterns. Clinical and histopathology data were obtained from
      electronic medical records. Imaging patterns and histopathology were analyzed for
      associations with metastatic spread and survival. RESULTS: Three distinct CT
      patterns of IHCC at presentation were identified: solitary dominant mass (type I
      IHCC, n = 34), dominant mass with satellite nodules in same segment (type II
      IHCC, n = 19), and multiple scattered hepatic lesions (type III IHCC, n = 39).
      Distant metastases developed in 49/92 patients (53%); 39 (42%) of which were
      present at diagnosis. Lungs (22/92; 24%), peritoneum (17/92; 18%), and bones
      (13/92; 14%) were most common metastatic sites. Type I IHCC had smaller size,
      lowest incidence of metastases at presentation, and best overall survival, while
      type III IHCC had shortest survival (p < 0.017). Poorly differentiated IHCC had
      higher proportion of osseous metastases (p = 0.042) and worse survival (p =
      0.027). CONCLUSION: IHCC has three distinct CT patterns at presentation with
      different prognoses. Knowledge of these patterns can help radiologists to detect
      the extrahepatic disease and predict prognosis.

PMID- 24869790
TI  - Histological grade of hepatocellular carcinoma correlates with arterial
      enhancement on gadoxetic acid-enhanced and diffusion-weighted MR images.
AB  - PURPOSE: To retrospectively determine the correlation between heptic tumor signal
      intensity on gadoxetic acid-enhanced and diffusion-weighted MR images and
      histopathological grading of hepatocellular carcinoma (HCC). METHODS: We
      retrospectively reviewed the MR images of 79 patients with 141 surgically
      resected HCCs. The signal intensity and its relationship with histopathological
      grade were assessed. We measured the apparent diffusion correlation (ADC) values
      and calculated arterial enhancement ratios, washout ratios, and relative
      intensity ratios of HCCs relative to the surrounding liver parenchyma in
      gadoxetic-enhanced MR images in order to determine their relationship to the
      histological grade. RESULTS: Morphological evaluation showed that larger tumor
      size and extrahepatic extension were associated with higher histologic grade (p <
      0.01). Multivariate logistic regression showed that low ADC value and low
      relative intensity ratio in the arterial phase (RIRa) predict high histological
      grade. ADC value (cut-off 1.7 * 10(-3) mm(2)/s, sensitivity 82.4%, specificity
      83.2%) was the best predictor of well-differentiated HCC, and RIRa (cut-off 0.93,
      sensitivity 81.4%, specificity 93.9%) was superior to ADC for predicting poorly
      differentiated HCC. CONCLUSION: Relative low arterial enhancement on gadoxetic
      acid-enhanced MR images and low ADC are predictive of worse histological grades
      of HCC.

PMID- 24869793
TI  - Photoinduced superwetting single-walled carbon nanotube/TiO(2) ultrathin network
      films for ultrafast separation of oil-in-water emulsions.
AB  - A SWCNT/TiO2 nanocomposite ultrathin film that has superhydrophilic and
      underwater superoleophobic properties after UV-light irradiation is successfully
      prepared by coating TiO2 via the sol-gel process onto an SWCNT ultrathin network
      film. The robust and flexible SWCNT/TiO2 nanocomposite films with a thickness and
      pore size of tens of nanometers can separate both surfactant-free and surfactant
      stabilized oil-in-water emulsions in an ultrafast manner with fluxes up to 30 000
      L m(-2) h(-1) bar(-1), which is 2 orders of magnitude higher than commercial
      filtration membranes with similar separation performance, and with high
      separation efficiency. Most importantly, the films exhibit excellent antifouling
      and self-cleaning performance during multiple cycles with the aid of the
      photocatalytic property of TiO2 nanoparticles. This work provides a route for
      designing ultrathin and superwetting films for effective separation of oil-in
      water emulsions. The SWCNT/TiO2 ultrathin film is potentially useful in treating
      emulsified wastewater produced in industry and daily life and for purification of
      crude oil and fuel. 

PMID- 24869792
TI  - Applications of memory alloy stent in vertebral fractures.
AB  - BACKGROUND: The aim of this study was to evaluate the feasibility of treating
      vertebral compression fractures using an autonomously developed nitinol memory
      alloy vertebral stent. MATERIAL AND METHODS: Thoracolumbar vertebral specimens
      from adult human cadavers were made into models of compression fractures. The
      models were divided into group A, which received percutaneous kyphoplasty (PKP),
      balloon dilation, and nitinol memory alloy vertebral stent implantation (PKP +
      nitinol stent group); group B, which received percutaneous vertebroplasty (PVP)
      and direct implantation of a nitinol memory alloy vertebral stent (PVP + nitinol
      stent group); and group C, which received PKP, balloon dilation, and bone cement
      vertebroplasty (PKP + polymethylmethacrylate (PMMA) group). Vertebral heights
      were measured before and after the surgery and the water bath incubation to
      compare the impact of the 3 different surgical approaches on reducing vertebral
      compression. RESULTS: The 3 surgical groups could all significantly restore the
      heights of compressed vertebral bodies. The vertebral heights of the PKP +
      nitinol stent group, PVP + nitinol stent group, and PKP + PMMA group were changed
      from the preoperative levels of (1.59+/-0.08) cm, (1.68+/-0.08) cm, and (1.66+/
      0.11) cm to the postoperative levels of (2.00+/-0.09) cm, (1.87+/-0.04) cm, and
      (1.99+/-0.09) cm, respectively. After the water bath, the vertebral heights of
      each group were changed to (2.10+/-0.07) cm, (1.98+/-0.09) cm, and (2.00+/-0.10)
      cm, respectively. Pairwise comparison of the differences between the preoperative
      and postoperative vertebral heights showed that group A and group B differed
      significantly (P=0.000); group B and group C differed significantly (P=0.003);
      and group A and group C had no significant difference (P=0.172). Pairwise
      comparison of the differences in the vertebral heights before and after the water
      bath showed that group A and group C differed significantly (P=0.000); group B
      and group C differed significantly (P=0.000); and group A and group B had no
      significant difference (P=0.157). CONCLUSIONS: The nitinol memory alloy stents
      can effectively support and reduce the compression of vertebral endplates and can
      be used to treat vertebral compression fractures without neurological symptoms.

PMID- 24869795
TI  - Revised Choi imaging criteria correlate with clinical outcomes in patients with
      metastatic renal cell carcinoma treated with sunitinib.
AB  - PURPOSE: To compare revised Choi criteria that incorporate concurrent size and
      attenuation changes at early follow-up imaging with Response Evaluation Criteria
      in Solid Tumors ( RECIST Response Evaluation Criteria in Solid Tumors ) 1.1 and
      original Choi criteria in stratification of clinical outcomes in patients with
      metastatic renal cell carcinoma ( mRCC metastatic renal cell carcinoma ) treated
      with sunitinib. MATERIALS AND METHODS: Institutional review board approved this
      retrospective study and waived informed consent. Baseline and first follow-up
      computed tomographic scans in 69 patients (50 men, 19 women; mean age, 60.3
      years; range, 19-83 years) with mRCC metastatic renal cell carcinoma treated with
      sunitinib from October 1, 2008, to March 1, 2013, were evaluated for tumor
      response by using RECIST Response Evaluation Criteria in Solid Tumors 1.1,
      original Choi criteria, and revised Choi criteria. Correlations with overall
      survival ( OS overall survival ) and progression-free survival ( PFS progression
      free survival ) were compared and stratified according to each radiologic
      criteria with Kaplan-Meier and multivariate Cox regression analysis. RESULTS:
      Median follow-up time was 29.7 months (95% confidence interval [ CI confidence
      interval ]: 18.9, 45.9). Response according to revised Choi criteria was
      independently correlated with OS overall survival (hazard ratio, 0.47 [95% CI
      confidence interval : 0.23, 0.99]; P = .046) and PFS progression-free survival
      (hazard ratio, 0.53 [95% CI confidence interval : 0.29, 0.99]; P = .047).
      Response according to RECIST Response Evaluation Criteria in Solid Tumors was not
      significantly correlated with OS overall survival (hazard ratio, 0.65 [95% CI
      confidence interval : 0.27, 1.58]; P = .344) or PFS progression-free survival
      (hazard ratio, 0.89 [95% CI confidence interval : 0.42, 1.91]; P = .768).
      Response according to original Choi criteria was not significantly correlated
      with OS overall survival (hazard ratio, 0.60 [95% CI confidence interval : 0.32,
      1.11]; P = .106) or PFS progression-free survival (hazard ratio, 0.59 [95% CI
      confidence interval : 0.34, 1.02]; P = .060). Median OS overall survival and PFS
      progression-free survival in responders according to revised Choi criteria was
      39.4 months (95% CI confidence interval : 9.1, upper limit not estimated) and
      13.7 months (95% CI confidence interval : 6.4, 24.6), respectively, compared with
      12.8 months (95% CI confidence interval : 8.7, 18.0) and 5.3 months (95% CI
      confidence interval : 3.9, 8.4), respectively, in nonresponders. CONCLUSION:
      Contemporaneous reduction in tumor size and attenuation were correlated with
      favorable clinical outcomes. Response according to revised Choi criteria showed
      better correlation with clinical outcomes compared with that according to RECIST
      Response Evaluation Criteria in Solid Tumors or original Choi criteria in
      patients with mRCC metastatic renal cell carcinoma treated with sunitinib.

PMID- 24869796
TI  - A prospective study of Romanian agriculture workers for zoonotic influenza
      infections.
AB  - BACKGROUND: In this prospective study we sought to examine seroepidemiological
      evidence for acute zoonotic influenza virus infection among Romanian agricultural
      workers. METHODS: Sera were drawn upon enrollment (2009) and again at 12 and 24
      months from 312 adult agriculture workers and 51 age-group matched controls.
      Participants were contacted monthly for 24 months and queried regarding episodes
      of acute influenza-like illnesses (ILI). Cohort members meeting ILI criteria
      permitted respiratory swab collections as well as acute and convalescent serum
      collection. Serologic assays were performed against 9 avian, 3 swine, and 3 human
      influenza viruses. RESULTS: During the two-year follow-up, a total of 23 ILI
      events were reported. Two subjects' specimens were identified as influenza A by
      rRT-PCR. During the follow-up period, three individuals experienced elevated
      microneutralization antibody titers >=1?80 against three (one each) avian
      influenza viruses: A/Teal/Hong Kong/w312/97(H6N1), A/Hong Kong/1073/1999(H9N2),
      or A/Duck/Alberta/60/1976(H12N5). However, none of these participants met the
      criteria for poultry exposure. A number of subjects demonstrated four-fold
      increases over time in hemagglutination inhibition (HI) assay titers for at least
      one of the three swine influenza viruses (SIVs); however, it seems likely that
      two of these three responses were due to cross-reacting antibody against human
      influenza. Only elevated antibody titers against A/Swine/Flanders/1/1998(H3N2)
      lacked evidence for such confounding. In examining risk factors for elevated
      antibody against this SIV with multiple logistic regression, swine exposure
      (adjusted OR = 1.8, 95% CI 1.1-2.8) and tobacco use (adjusted OR = 1.8; 95% CI
      1.1-2.9) were important predictors. CONCLUSIONS: While Romania has recently
      experienced multiple incursions of highly pathogenic avian influenza among
      domestic poultry, this cohort of Romanian agriculture workers had sparse evidence
      of avian influenza virus infections. In contrast, there was evidence, especially
      among the swine exposed participants, of infections with human and one swine H3N2
      influenza virus.

PMID- 24869797
TI  - The role of isoflavone metabolism in plant protection depends on the
      rhizobacterial MAMP that triggers systemic resistance against Xanthomonas
      axonopodis pv. glycines in Glycine max (L.) Merr. cv. Osumi.
AB  - Glycine max (L.) Merr. plays a crucial role in both the field of food and the
      pharmaceutical industry due to their input as plant protein and to the benefits
      of isoflavones (IF) for health. In addition, IF play a key role in nodulation and
      plant defense and therefore, an increase in IF would be desirable for better
      field performance. IF are secondary metabolites and therefore, inducible, so
      finding effective agents to increase IF contents is interesting. Among these
      agents, plant growth promoting rhizobacteria (PGPR) have been used to trigger
      systemic induction of plant's secondary metabolism through their microbe
      associated molecular patterns (MAMPs) that fit in the plant's receptors to start
      a systemic response. The aim of this study was to evaluate the ability of 4 PGPR
      that had a contrasted effect on IF metabolism, to protect plants against biotic
      stress and to establish the relation between IF profile and the systemic response
      triggered by the bacteria. Apparently, the response involves a lower sensitivity
      to ethylene and despite the decrease in effective photosynthesis, growth is only
      compromised in the case of M84, the most effective in protection. All strains
      protected soybean against Xanthomonas axonopodis pv. glycines (M84 > N5.18 >
      Aur9>N21.4) and only M84 and N5.18 involved IF. N5.18 stimulated accumulation of
      IF before pathogen challenge. M84 caused a significant increase on IF only after
      pathogen challenge and N21.4 caused a significant increase on IF content
      irrespective of pathogen challenge. Aur9 did not affect IF. These results point
      out that all 4 strains have MAMPs that trigger defensive metabolism in soybean.
      Protection induced by N21.4 and Aur9 involves other metabolites different to IF
      and the role of IF in defence depends on the previous metabolic status of the
      plant and on the bacterial MAMP. 

PMID- 24869798
TI  - Polyamine biosynthesis and degradation are modulated by exogenous gamma
      aminobutyric acid in root-zone hypoxia-stressed melon roots.
AB  - We detected physiological change and gene expression related to PA metabolism in
      melon roots under controlled and hypoxic conditions with or without 5 mM GABA.
      Roots with hypoxia treatment showed a significant increase in glutamate
      decarboxylase (GAD) activity and endogenous GABA concentration. Concurrently, PA
      biosynthesis and degradation accelerated with higher gene expression and enzymes
      activity. However, endogenous GABA concentrations showed a large and rapid
      increase in Hypoxia + GABA treated roots. This led to a marked increase in Glu
      concentration by feedback inhibition of GAD activity. Hypoxia + GABA treatment
      enhanced arginine (Arg), ornithine (Orn) and methionine (Met) levels, promoting
      enzyme gene expression levels and arginine decarboxylase (ADC), ornithine
      decarboxylase (ODC) and S-adenosylmethionine decarboxylase (SAMDC) activities in
      roots. Hypoxia + GABA treatment significantly increased concentrations of free
      putrescine (Put), spermidine (Spd) and spermine (Spm) from day two to eight,
      promoting the PA conversion to soluble conjugated and insoluble bound forms.
      However, PA degradation was significantly inhibited in hypoxia + GABA treated
      roots by significantly decreasing gene expression and activity of diamine oxidase
      (DAO) and polyamine oxidase (PAO). However, exogenous GABA showed a reduced
      effect in control compared with hypoxic conditions. Our data suggest that
      alleviating effect of exogenous GABA to hypoxia is closely associated with
      physiological regulation of PA metabolism. We propose a potential negative
      feedback mechanism of higher endogenous GABA levels from combined effects of
      hypoxia and exogenous GABA, which alleviate the hypoxia damage by accelerating PA
      biosynthesis and conversion as well as preventing PA degradation in melon plants.

PMID- 24869799
TI  - Body mass index, diabetes, and triple-negative breast cancer prognosis.
AB  - Higher body mass index (BMI) and diabetes are associated with worse breast cancer
      prognosis. However, few studies have focused on triple-negative breast cancer
      (TNBC). The goal of this study is to examine this association in a cohort of
      patients with TNBC. We retrospectively reviewed 501 consecutive patients with
      TNBC seen at the Washington University Breast Oncology Clinic. Cox proportional
      hazard models were used to determine the relationship between BMI and diabetes at
      diagnosis with overall survival (OS) and disease free survival (DFS). Four
      hundred and forty-eight patients had BMI recorded and 71 patients had diabetes.
      The median age at diagnosis was 53 (23-98) years and follow-up was 40.1 months
      (IQR 25.2-62.9). Baseline BMI and diabetes were not associated with OS or DFS. OS
      hazard ratios (HRs) for patients who were overweight (BMI 25.0-29.99), with class
      I obesity (BMI 30-34.99), or BMI >=35 were 1.22 (CI 0.78-1.91), 0.92 (CI 0.59
      1.43), and 1.16 (CI 0.70-1.90), respectively. The HRs for DFS in patients who
      were overweight, with class I obesity, or BMI >=35 were 1.01 (CI 0.65-1.56), 0.94
      (CI 0.60-1.47), and 0.99 (CI 0.63-1.57), respectively. Similarly, the HRs for
      diabetics were 1.27 (CI 0.82-1.96) for OS and 0.98 (CI 0.64-1.51) for DFS.
      Obesity and diabetes did not significantly affect survival for patients with TNBC
      in this study. 

PMID- 24869800
TI  - Application of the intermediate derivatization approach in agrochemical
      discovery.

PMID- 24869801
TI  - Identification of clinical features and autoantibodies associated with calcinosis
      in dermatomyositis.
AB  - IMPORTANCE: Prior studies have estimated that up to 20% of adults with
      dermatomyositis (DM) have calcinosis, which can lead to significant morbidity.
      Identification of risk factors may provide a better understanding of the
      pathogenesis and ultimately therapy for this difficult clinical problem. Risk
      factors for calcinosis in adults with DM have not been extensively studied.
      OBJECTIVES: To determine the prevalence of calcinosis and to identify associated
      clinical features in a cohort of extensively phenotyped adults with DM. DESIGN,
      SETTING, AND PARTICIPANTS: A cross-sectional study of 126 patients diagnosed as
      having DM from January 1, 2006, through January 1, 2013, was performed. Patients
      were adults (>=18 years of age) attending the Stanford University Medical Center
      clinic. MAIN OUTCOMES AND MEASURES: Calcinosis, defined as the presence of
      calcium deposition in the skin and subcutaneous tissues on physical examination.
      RESULTS: Fourteen patients (11.1%) had calcinosis, with the extremities most
      commonly involved. Patients with vs those without calcinosis had a longer disease
      duration (median, 6.9 years; range, 2.4-18.1; vs median, 3.9 years; range, 0.2
      19.2 years; P = .003) and more fingertip ulcers (50.0% vs 9.3%, P < .001). An
      association between calcinosis and both interstitial lung disease and anti-MDA-5
      autoantibodies was identified, but this association did not persist in
      multivariate models that adjusted for fingertip ulcers. Fingertip ulcers and
      disease duration were strongly associated with calcinosis in all multivariate
      models, independent of the underlying autoantibody present. Autoantibodies to NXP
      2 were associated with calcinosis (odds ratio, 15.52; 95% CI, 2.01-119.90),
      whereas anti-transcriptional intermediary factor 1-gamma antibodies were
      protective (odds ratio, 0.2; 95% CI, 0.01-0.99) in multivariate analyses that
      adjusted for fingertip ulcers and other covariates. CONCLUSIONS AND RELEVANCE:
      Calcinosis was a relatively uncommon clinical feature in our cohort of adults
      with DM. Our data suggest that calcinosis is positively associated with longer
      disease duration, fingertip ulcers, and NXP-2 autoantibodies and negatively
      associated with transcriptional intermediary factor 1-gamma antibodies. A common
      vascular mechanism may underlie the development of both calcinosis and fingertip
      ulcers in patients with DM.

PMID- 24869802
TI  - Fluoride in the bones of foxes (Vulpes vulpes Linneaus, 1758) and raccoon dogs
      (Nyctereutes procyonoides Gray, 1834) from North-Western Poland.
AB  - Assessment of exposure to fluoride (F(-)) is increasingly focused on mineralized
      tissues, mainly bones. Their periodic growth and continuous reconstruction make
      them a good material for studying long-term F(-) accumulation. In this study, F(
      )concentrations were determined in the bones of foxes and raccoon dogs from north
      western Poland and relationships between bone F(-) and the age categories of the
      animals were attempted to be identified. Bone samples were collected from femurs
      of 32 foxes (15 males and 17 females) and 18 raccoon dogs (10 males and 8
      females) from polluted, medium-polluted, and unpolluted by F(-) areas. Bone F(-)
      was determined by potentiometric method, and results were expressed per dry
      weight (dw); they ranged from 176 to 3,668 mg/kg dw in foxes and from 84 to 1,190
      mg/kg dw in raccoon dogs. Foxes from north-western Poland accumulated much more
      F(-) in their bones than raccoon dogs. Our study shows that the assessment of
      hazards created by industrial emitters can be conducted conveniently by the
      measurements of fluorine content in hard tissues of wild animals. Due to
      availability of such type of material for studies, it seems that the analysis of
      fluoride content in bones can be a good tool in the development of ecotoxicology.

PMID- 24869803
TI  - Distribution of graphene oxide and TiO2-graphene oxide composite in A549 cells.
AB  - Graphene and its derivatives are increasingly applied in nanoelectronics,
      biosensing, drug delivery, and biomedical applications. However, the information
      about its cytotoxicity remains limited. Herein, the distribution and cytotoxicity
      of graphene oxide (GO) and TiO2-graphene oxide composite (TiO2-GO composite) were
      evaluated in A549 cells. Cell viability and cell ultrastructure were measured.
      Our results indicated that GO could enter A549 cells and located in the cytoplasm
      and nucleus without causing any cell damage. TiO2 nanoparticles and GO would be
      separated after TiO2-GO composite entered A549 cells. TiO2-GO composite could
      induce cytotoxicity similar to TiO2 nanoparticles, which was probably attributed
      to oxidative stress. These results should be considered in the development of
      biological applications of GO and TiO2-GO composite. 

PMID- 24869804
TI  - An oncogenic kinase: putting PAK5 forward.
AB  - INTRODUCTION: Overexpression of p21-activated kinase 5 (PAK5) is discovered in
      many tumors, probably due to its regulation in cytoskeleton, antiapoptosis and
      proliferation. A better understanding of the modulation mechanisms of PAK5 is
      needed for the development of tumor treatment where current therapeutics is
      inadequate. AREAS COVERED: This review discusses the current understanding of
      PAK5 functions as an oncogenic kinase in tumor cellular regulation. Mechanisms of
      action and molecular pathways involved in cytoskeleton regulation, antiapoptosis
      and proliferation of tumors are discussed. EXPERT OPINION: PAKs are
      serine/threonine kinases and downstream effectors for Cdc42 and Rac, the
      subfamilies of Rho small GTPases. PAK5 shares sequence identities in p21-GTPase
      binding domain and kinase domain and is completely different in other regions
      compared with other PAKs. Overexpression of PAK5 has been found in several
      tumors, probably due to its contribution to proliferation, cytoskeleton and anti
      apoptosis. Additional regulation mechanisms which are independent of Rho GTPases
      also indicate that PAK5 functions as a special signal molecule in cellular
      signaling pathways of tumor progression.

PMID- 24869806
TI  - Simple methods of determining confidence intervals for functions of estimates in
      published results.
AB  - Often, the reader of a published paper is interested in a comparison of
      parameters that has not been presented. It is not possible to make inferences
      beyond point estimation since the standard error for the contrast of the
      estimated parameters depends upon the (unreported) correlation. This study
      explores approaches to obtain valid confidence intervals when the correlation
      [Formula: see text] is unknown. We illustrate three proposed approaches using
      data from the National Health Interview Survey. The three approaches include the
      Bonferroni method and the standard confidence interval assuming [Formula: see
      text] (most conservative) or [Formula: see text] (when the correlation is known
      to be non-negative). The Bonferroni approach is found to be the most
      conservative. For the difference in two estimated parameter, the standard
      confidence interval assuming [Formula: see text] yields a 95% confidence interval
      that is approximately 12.5% narrower than the Bonferroni confidence interval;
      when the correlation is known to be positive, the standard 95% confidence
      interval assuming [Formula: see text] is approximately 38% narrower than the
      Bonferroni. In summary, this article demonstrates simple methods to determine
      confidence intervals for unreported comparisons. We suggest use of the standard
      confidence interval assuming [Formula: see text] if no information is available
      or [Formula: see text] if the correlation is known to be non-negative. 

PMID- 24869807
TI  - Taxonomic status of the subgenus Conoblasta Forster 1869 of the genus Glypta
      Gravenhorst 1829 with revision of Japanese species (Hymenoptera, Ichneumonidae,
      Banchinae).
AB  - The Japanese species of subgenus Conoblasta Forster 1869 sensu Aubert (1978) and
      Kuslitzky (1974, 2007) of the genus Glypta Gravenhorst 1829 are reviewed. No
      reliable synapomorphies are found for the species of Conoblasta after all and
      thus we conclude that they should be treated as a tentative species group.
      Eighteen species of the Conoblasta species group, including 11 new species (G.
      cognata sp. nov., G. daisetsuzana sp. nov., G. densepunctata sp. nov., G.
      flavitarsus sp. nov., G. ichitai sp. nov., G. karasawensis sp. nov., G. nipponica
      sp. nov., G. shigaensis sp. nov., G. suwai sp. nov., G. touyaensis sp. nov., G.
      zenibakoensis sp. nov.) and two newly recorded species (G. chinensis (Uchida
      1956) and G. extincta Ratzeberg 1852), are recognized from Japan. A key to the
      Japanese species is provided.

PMID- 24869809
TI  - An illustrated key to the New World genera of Philonthina Kirby (Coleoptera:
      Staphylinidae), with morphological, taxonomical and distributional notes.
AB  - An illustrated key to the 29 genera of Philonthina currently known in the New
      World is provided, based on adult morphological characters. Updated information
      on the morphology, taxonomic history, bionomics and distribution of the
      Philonthina in the study area is also provided. 

PMID- 24869808
TI  - Stone loaches of Choman River system, Kurdistan, Iran (Teleostei: Cypriniformes:
      Nemacheilidae).
AB  - For the first time, we present data on species composition and distributions of
      nemacheilid loaches in the Choman River basin of Kurdistan province, Iran. Two
      genera and four species are recorded from the area, of which three species are
      new for science: Oxynoemacheilus kurdistanicus, O. zagrosensis, O. chomanicus
      spp. nov., and Turcinoemacheilus kosswigi Ban. et Nalb. Detailed and illustrated
      morphological descriptions and univariate and multivariate analysis of
      morphometric and meristic features are for each of these species. Forty
      morphometric and eleven meristic characters were used in multivariate analysis to
      select characters that could discriminate between the four loach species.
      Discriminant Function Analysis revealed that sixteen morphometric measures and
      five meristic characters have the most variability between the loach species. The
      dendrograms based on cluster analysis of Mahalanobis distances of morphometrics
      and a combination of both characters confirmed two distinct groups:
      Oxynoemacheilus spp. and T. kosswigi. Within Oxynoemacheilus, O. zagrosensis and
      O. chomanicus are more similar to one other rather to either is to O.
      kurdistanicus. 

PMID- 24869805
TI  - Attitudes of people in the UK with HIV who Are Antiretroviral (ART) Naive to
      starting ART at high CD4 counts for potential health benefit or to prevent HIV
      transmission.
AB  - OBJECTIVE: To assess if a strategy of early ART to prevent HIV transmission is
      acceptable to ART naive people with HIV with high CD4 counts. DESIGN: ASTRA is a
      UK multicentre, cross sectional study of 3258 HIV outpatients in 2011/12. A self
      completed questionnaire collected sociodemographic, behavioral and health data,
      and attitudes to ART; CD4 count was recorded from clinical records. METHODS: ART
      naive participants with CD4 >=350 cells/uL (n = 281) were asked to
      agree/disagree/undecided with the statements (i) I would want to start treatment
      now if this would slightly reduce my risk of getting a serious illness, and (ii)
      I would want to start treatment now if this would make me less infectious to a
      sexual partner, even if there was no benefit to my own health. RESULTS:
      Participants were 85% MSM, 76% white, 11% women. Of 281 participants, 49.5% and
      45.2% agreed they would start ART for reasons (i) and (ii) respectively; 62.6%
      agreed with either (i) or (ii); 12.5% agreed with neither; 24.9% were uncertain.
      Factors independently associated (p<0.1) with agreement to (i) were: lower CD4,
      more recent HIV diagnosis, physical symptoms, not being depressed, greater
      financial hardship, and with agreement to (ii) were: being heterosexual, more
      recent HIV diagnosis, being sexually active. CONCLUSIONS: A strategy of starting
      ART at high CD4 counts is likely to be acceptable to the majority of HIV
      diagnosed individuals. Almost half with CD4 >350 would start ART to reduce
      infectiousness, even if treatment did not benefit their own health. However a
      significant minority would not like to start ART either for modest health benefit
      or to reduce infectivity. Any change in approach to ART initiation must take
      account of individual preferences. Transmission models of potential benefit of
      early ART should consider that ART uptake may be lower than that seen with low
      CD4 counts.

PMID- 24869810
TI  - A new species of Brevipalpus Donnadieu (Acari: Tenuipalpidae) and key to the
      Egyptian species.
AB  - A new species, Brevipalpus noranae sp. nov. (Acari: Tenuipalpidae) is described
      and illustrated from females collected on Malus domestica Borkh and Citrus
      aurantium L. A key to the species of the genus Brevipalpus present in Egypt is
      provided. 

PMID- 24869811
TI  - New data on the morphology and distribution of the enigmatic Schouteden's sun
      snake, Helophis schoutedeni (de Witte, 1922) from the Congo Basin.

PMID- 24869812
TI  - On some Vetigastropoda (Mollusca, Gastropoda) from the Plio-Pleistocene of the
      Philippines with descriptions of three new species.
AB  - We studied representatives of seven vetigastropod families in an extremely well
      preserved Plio-Pleistocene mollusc fauna found in relatively deep water sediments
      (c. 200-300 m paleodepth) from the north-western Philippines. The fauna is
      systematically described and its paleoenvironmental and paleobiogeographical
      character is explored. Twenty-six species of gastropods were studied, three of
      which are described as new: Halystina conoidea n. sp., Calliotropis arenosa n.
      sp. and Ethminolia wareni n. sp. Four new combinations are proposed:
      Pseudotalopia taiwanensis (Chen, 2006), Solariella segersi (Poppe, Tagaro &
      Dekker, 2006), Zetela tabakotanii (Poppe, Tagaro & Dekker, 2006) and Ilanga konos
      (Vilvens, 2009). Fourteen species are known living. Most extant species nowadays
      occur around the Philippines. Two of the species also occur in Neogene deposits
      from western Pacific islands. The new fauna offers insights into the character of
      relatively deep water Indo-West Pacific mollusc faunas prior to the onset of the
      late Quaternary ice ages.

PMID- 24869813
TI  - Identification and character analysis of the Acerentomidae (Protura) of the
      northeastern Palearctic (Protura: Acerentomidae).
AB  - This paper is a summary of proturan fauna from Siberia and the Russian Far East,
      collectively termed the northeastern Palearctic. Special attention is given to
      the analysis of Acerentomidae, which is extraordinarily diverse in these regions
      (31 species). A key to species and a brief exposition of distribution of each
      genus are provided. A redescription of Imadateiella sharovi is presented,
      additional morphological characters are added for Nipponentomon khabarovskense,
      N. bidentatum, Yamatentomon yamato and Callientomon chinensis, and additional
      collection data are given for Y. yamato, C. chinensis, Nipponentomon jaceki and
      N. nippon. A cladistic analysis is presented of hypothetical relationships among
      the discussed acerentomid taxa. A scheme for ventral porotaxy is proposed, and
      the taxonomic importance of porotaxic characters within Acerentomata is
      discussed. Some biogeographical and phylogenetic considerations are given.

PMID- 24869814
TI  - A revision of the genus Protarchanara Beck, 1999 with description of a new genus
      and three new species (Lepidoptera, Noctuidae, Xyleninae).
AB  - The genus Protarchanara Beck, 1999 is revised. The new genus Hydredes gen. n.
      (type species Hydredes yakobsoni sp. n.) is described. Three new species,
      Hydredes yakobsoni sp. n., H. shchetkini sp. n. and Protarchanara mythimnoida sp.
      n. are described from Central Asia. Two species, Arenostola delattini Wiltshire,
      1953 and Hydraecia praecipua Hacker & Nekrasov, 2001 are transferred to the genus
      Hydredes gen. n. Protarchanara brevilinea impudica (Staudinger, 1892) stat. n. is
      upgraded to subspecific level. Lectotypes for Namangana contumax Pungeler, 1902,
      Sidemia (Luperina) johni Pungeler, 1914 and Nonagria impudica Staudinger, 1892
      are designated. The adults and male and female genitalia are illustrated.

PMID- 24869816
TI  - Two new species of Mesostrix Mazur, 1994 (Coleoptera: Histeridae) from Southeast
      Asia.

PMID- 24869815
TI  - Additional morphological information on Dipteropeltis hirundo Calman, 1912, and a
      description of Dipteropeltis campanaformis n. sp. (Crustacea: Branchiura) from
      two characiform benthopelagic fish hosts from two Northern rivers of the
      Brazilian Amazon.
AB  - Dipteropeltis is a monotypic genus of the Branchiura and endemic to South
      America. Twelve specimens of Dipteropeltis sp. and micrographs of a thirteenth
      specimen were obtained from four institutions. Measurements and light micrographs
      were taken of all the specimens. The specimens were compared to all known
      descriptions of D. hirundo and sorted into two groups, those that conformed to
      the description of D. hirundo; and those that differed morphologically. Two
      specimens, one from each group  were stained with lignin pink and subsequently
      prepared for Scanning Electron Microscopy. The differences observed in the
      specimens indicated that a new species exists. Thus, Dipteropeltis campanaformis
      n. sp. is described from seven specimens collected from two characiform
      benthopelagic fish species and compared to D. hirundo. Dipteropeltis
      campanaformis n. sp. differs from D. hirundo in the head shape, the length and
      shape of the carapace lobes, the membrane composition of the maxillules, the
      shape of the maxillae, the shape of the mouth, and the shape of the natatory
      lobes. 

PMID- 24869817
TI  - Review of the grassland leafhopper genus Nephotettix Matsumura (Hemiptera:
      Cicadellidae: Deltocephalinae: Chiasmini) from the Chinese mainland.
AB  - The Chinese mainland species of the leafhopper genus Nephotettix Matsumura
      (Hemiptera: Cicadellidae: Deltocephalinae: Chiasmini) (Nephotettix cincticeps
      (Uhler), Nephotettix malayanus Ishihara & Kawase, Nephotettix nigropictus (Stal),
      Nephotettix parvus Ishihara & Kawase rec. n., and Nephotettix virescens
      (Distant)) are reviewed. This genus is redescribed. Variation is described and
      illustrated. Keys for their separation are provided together with a worldwide
      checklist. 

PMID- 24869818
TI  - Spazigasteroides a new genus from China with a black face and scutellum in the
      Syrphini (Diptera: Syrphidae).
AB  - In the present paper, the genus Spazigasteroides gen. nov. (Diptera, Syrphidae),
      with Spazigasteroides caeruleus sp. nov. as type species, is described from
      China. The new genus bears the following characters: Head strongly concave
      posteriorly and closely appressed to thorax so that the bare postpronota are
      entirely hidden. Face black in ground colour. Antennae short, with
      basoflagellomeres slightly longer than wide. Scutellum black. Postmetacoxal
      bridge <a name="RTF4f004c0045005f004c004900" incomplete. Legs simple, slender.
      Wing vein R 4+5 straight, vein r-m at basal third of cell dm. Abdomen petiolate,
      longer than head and thorax together. Male aedeagus two segmented. Based on the
      subdivision of Syrphinae by Vockeroth (1992), the new genus belongs to the tribe
      Syrphini, it is separated from the genera of the tribe Syrphini by both the face
      and scutellum black. In appearance the new genus is also similar to the genus
      Spazigaster Rondani, the tribe Bacchini, but it is differentiated from the genera
      of the tribe Bacchini by the two segmented aedeagus.

PMID- 24869819
TI  - Cottus schitsuumsh, a new species of sculpin (Scorpaeniformes: Cottidae) in the
      Columbia River basin, Idaho-Montana, USA.
AB  - Fishes of the genus Cottus have long been taxonomically challenging because of
      morphological similarities among species and their tendency to hybridize, and a
      number of undescribed species may remain in this genus. We used a combination of
      genetic and morphological methods to delineate and describe Cottus schitsuumsh,
      Cedar Sculpin, a new species, from the upper Columbia River basin, Idaho-Montana,
      USA. Although historically confused with the Shorthead Sculpin (C. confusus), the
      genetic distance between C. schitsuumsh and C. confusus (4.84-6.29%) suggests
      these species are distant relatives. Moreover, the two species can be
      differentiated on the basis of lateral-line pores on the caudal peduncle, head
      width, and interpelvic width. Cottus schitsuumsh is also distinct from all other
      Cottus in this region in having a single small, skin-covered, preopercular spine.
      Haplotypes of mtDNA cytochrome oxidase c subunit 1 of C. schitsuumsh differed
      from all other members of the genus at three positions, had interspecific genetic
      distances typical for congeneric fishes (1.61-2.74% to nearest neighbors), and
      were monophyletic in maximum-likelihood trees. Microsatellite analyses confirmed
      these taxonomic groupings for species potentially sympatric with C. schitsuumsh
      and that fish used in morphological comparisons were unlikely to be introgressed.
      Its irregular distribution, in the Spokane River basin in Idaho and portions of
      the Clark Fork River basin in Montana, may have resulted from human-assisted
      translocation. 

PMID- 24869820
TI  - A new genus with six new species of Typhlopolycystidinae Evdonin, 1977
      (Platyhelminthes, Kalyptorhynchia, Polycystididae).
AB  - Five new species of the new taxon Brunetorhynchus n. gen. are described: B.
      deconincki n. sp., B. microstylis n. sp. and B. complicatus n. sp. are from the
      Mediterranean, B. canariensis n. sp. is from the Canary Island Lanzarote, B.
      cannoni n. sp. is from the Australian East coast and one species from the
      Galapagos, formerly described as Limipolycystis spec., is transferred to the new
      genus as B. dubius n. sp.. As in Limipolycystis, these species have a single
      stylet, (accessory stylet type II), an accessory secretion vesicle (type II) and
      a prostate vesicle (type III) in the male atrium, although the latter vesicle is
      absent in some species. Unlike the species of Limipolycystis, where the seminal
      receptacle is a sclerotized tubule, the species of the new taxon have a pear
      shaped seminal receptacle on the oviduct.  

PMID- 24869821
TI  - Cnemaspis rammalensis sp. nov., Sri Lanka's largest day-gecko (Sauria:
      Gekkonidae: Cnemaspis) from Rammalakanda Man and Biosphere Reserve in southern
      Sri Lanka.
AB  - A new species of rock dwelling gecko belonging to the genus Cnemaspis is
      described from Sri Lanka based on a suite of morphological features. The species
      is the largest of its genus described from Sri Lanka so far (snout-vent length 52
      54 mm) and is the second largest of the Western Ghats-Sri Lanka Biodiversity
      Hotspot. It may be diagnosed in details of both scalation (ventrals186-207; mid
      subcaudals large; absence of precloacal pores; 15 femoral pores on each side; 22
      23 and 23-25 subdigital lamellae on finger IV and on toe IV, respectively; smooth
      scales on tail dorsum) and colouration (five prominent trilobate shaped cream
      markings pointing towards head and extending from neck to vent).The species is
      found in a unique habitat in the Rammalakanda Forest, where it is threatened by
      deforestation. 

PMID- 24869822
TI  - A new species of Grapholita Treitschke (Lepidoptera: Tortricidae) from the
      midwestern USA.
AB  - Grapholita orbexilana, new species, is described from Illinois, Kentucky, and
      Ohio, USA. The larvae feed exclusively on Orbexilum onobrychis (Fabaceae), a
      plant of conservation interest in the Midwest. The moth is univoltine; its
      complete annual life cycle is detailed. Adult morphology readily distinguishes G.
      orbexilana from all other midwestern species of Grapholita; diagnostic
      information is provided. Observations on morphology, larval host plant
      preference, and pheromone attraction are presented to support the assignment of
      G. orbexilana to the jungiella species group of the subgenus Grapholita. 

PMID- 24869823
TI  - Eviota piperata, a new gobiid species from Palau (Teleostei: Gobiidae).
AB  - A new species of dwarfgoby, Eviota piperata is described from Palau. It belongs
      to the cephalic sensory-pore system Group II (lacking only the IT pore); has a
      dorsal/anal-fin formula of 8/8; has some pectoral-fin rays branched; no dark spot
      over the ural centrum; the male genital papilla is not fimbriate; and the cheek
      and body are heavily peppered with chromatophores. 

PMID- 24869824
TI  - A revision of the subgenus Bessobates of the genus Netelia from Japan
      (Hymenoptera, Ichneumonidae, Tryphoninae).
AB  - Japanese species of the genus Netelia of the subgenus Bessobates are revised.
      Fourteen species are recognized. Four new species, N. (B.) longipad, N. (B.)
      nigridorsalis, N. (B.) nodai and N. (B.) yakushimensis, are described. Six
      species, N. (B.) comitor Tolkanitz, 1974, N. (B.) frenata Tolkanitz, 1981, N.
      (B.) gansuana (Kokujev, 1906), N. (B.) kiuhabona (Uchida, 1928), N. (B.) nanaki
      Kaur & Jonathan, 1979 and N. (B.) pallescens (Schmiedeknecht, 1910) are recorded
      from Japan for the first time and redescribed based on Japanese specimens. Male
      genitalia of N. (B.) yamatoensis (Uchida, 1934) are figured and described for the
      first time. Netelia (Bessobates) odaiensis (Uchida, 1934) is removed from synonym
      with virgata and treated as species incertae sedis. Three species, N. (B.)
      cristata (Thomson, 1888), N. (B.) latungula (Thomson, 1888) and N. (B.) virgata
      (Geoffroy, 1785) are redescribed based on Japanese specimens. A key to 14
      Japanese species is given.

PMID- 24869825
TI  - Checklist of the New Zealand Heteroptera (Insecta: Hemiptera): an update based on
      the 2004 to 2013 literature.
AB  - An updated checklist of the New Zealand Heteroptera (Insecta: Hemiptera) is
      provided as a supplement to the "Heteroptera (Insecta: Hemiptera): catalogue" of
      Lariviere and Larochelle (2004: Fauna of New Zealand 50). A total of 142 genera
      and 319 species belonging to 28 families are recorded for New Zealand. Changes to
      the 2004 catalogue are documented. The synonymy and primary type information of
      taxa described between 2004 and July 2013 are also given. The presence of the
      anthocorid Macrotrachelia nigronitens in New Zealand is confirmed. 

PMID- 24869826
TI  - A new species of Palpomyia Meigen (Diptera: Ceratopogonidae) described in all
      life stages from Shillong plateau, India .
AB  - Life stages of Palpomyia sohraensis sp. n. is described and illustrated with bio
      ecological notes. Key to the adult of the all species from India of the genus
      Palpomyia Meigen is also provided. The complete life stages of any Palpomyia are
      described for the first time from the Oriental Region. 

PMID- 24869827
TI  - Description of Dociostaurus biskrensis sp. nov. and male allotypes of four
      species: Pamphagulus bodenheimeri dumonti, P. uvarovi, Sphingonotus ebneri and
      Notopleura pygmaea (Orthoptera: Acridoidea) in the region of Biskra, Algeria.
AB  - The new species Dociostaurus biskrensis Moussi & Petit 2013 was collected in the
      region of Biskra, at the arido-Saharan limit of Eastern Algerian. We also
      describe the males of four species for which only females were known: Pamphagulus
      bodenheimeri dumonti, P. uvarovi, Notopleura pygmaea and Sphingonotus ebneri. The
      key to the genus Dociostaurus in North Africa is given. The species P. uvarovi
      and Notopleura pygmaea are new for the Algeria. The diets and life cycles of D.
      biskrensis and of the two species of Pamphagulus are defined. 

PMID- 24869828
TI  - Glesirhanis bercioi, a new genus and species from Baltic amber (Coleoptera:
      Endomychidae: Leiestinae) with a checklist and nomenclatural notes regarding
      fossil Endomychidae.
AB  - A new genus and species of handsome fungus beetle, Glesirhanis bercioi gen. nov.,
      sp. nov. (Coleoptera: Endomychidae: Leiestinae) is described from Baltic amber.
      The newly described genus is compared with all known extant and extinct genera of
      the subfamily. A key to the genera of Leiestinae including fossils and a
      checklist of fossil Endomychidae are provided. The status of two taxa previously
      placed in Endomychidae, Palaeoendomychus gymnus Zhang and Tetrameropsis mesozoica
      Kirejtshuk & Azar, is discussed, and a new status for the latter, elevating it to
      the family-level as Tetrameropseidae status nov., is proposed. 

PMID- 24869829
TI  - Description of two new species of Microhyla (Anura: Microhylidae) from
      Bangladesh.
AB  - Two new frog species belonging to genus Microhyla from the southeast, central and
      northeast regions of Bangladesh are described. Based on a molecular phylogeny
      derived from mitochondrial DNA sequences, one of the new species forms a clade
      with M. fissipes, while the second new species is sister to this clade. The DNA
      sequences of the mitochondrial cytochrome b gene from these new species are
      substantially diverged from M. fissipes (8.9 and 10.2% [3.6 and 4.2% for 16S
      ribosomal RNA gene] uncorrected pairwise divergence, respectively), and the
      estimated phylogenetic splits from their closest relative is in the Pliocene (3.4
      Mya) and middle Miocene (10.5 Mya). The first new species (Microhyla mukhlesuri
      sp. nov.) can be diagnosed from its nearest congener (M. fissipes) by the
      following characteristics: SVL: 16.5-21.0 mm, finger length 1 < 4 < 2 < 3, tips
      of finger and toes not swollen, subarticular tubercles distinct, an inverse U
      shaped mark on the anus, and a distinct X-shaped marking on the dorsum. Although
      the second new species (M. mymensinghensis sp. nov.) shares some morphological
      characteristics with the first new species, it can be readily diagnosed from its
      close congeners by its longer hindlimbs (HLL/SVL), tibia (TIL/SVL) and forearm
      width (FAW/SVL), in addition to a combination of the following characteristics:
      SVL: 14.2-21.3 mm, snout truncate, a crescent-shaped marking on the anus, and an
      X-shaped marking on the dorsum. The tibio-tarsal articulation extends to the eye
      in M. fissipes but ranges from the eye to the tip of the snout in the two new
      species.  

PMID- 24869830
TI  - Chewing lice (Phthiraptera: Amblycera and Ischnocera) from wild birds in southern
      Vietnam, with descriptions of two new species.
AB  - A total of 239 individuals of 50 bird species were examined for chewing lice
      (Insecta: Phthiraptera) in southern Vietnam. Fifty-six birds of 20 species were
      parasitised by 15 species of lice belonging to 10 genera from two suborders,
      Amblycera: Menacanthus, Meromenopon, Myrsidea, and Ischnocera: Alcedoecus,
      Brueelia, Cuculicola, Meropoecus, Penenirmus, Philopteroides and Philopterus.
      Thirteen louse samples from Passeriformes were identified to genus only because
      they contain inadequate material. A total of 29 host-louse associations were
      found, of which nine are new, including: (1) two new species of the genus
      Brueelia, which are described and named in this paper: Brueelia binhchauensis
      from Megalaima lineata (Vieillot, 1816) (Piciformes: Megalaimidae), and Brueelia
      malacocincla from Malacocincla abbotti Blyth, 1845 (Passeriformes: Pellorneidae);
      (2) first records of lice from Cyornis hainanus (Ogilvie-Grant, 1900); and (3)
      the first record of Myrsidea claytoni Hellenthal & Price, 2003 from Cymbirhynchus
      macrorhynchos (Gmelin, 1788) (Passeriformes: Eurylaimidae), here regarded as a
      case of natural host-switching. A portion of the mitochondrial cytochrome oxidase
      I (COI) gene for some species of chewing lice was sequenced in order to assess
      their genetic divergences. 

PMID- 24869831
TI  - A new species of karst forest-adapted Bent-toed Gecko (genus Cyrtodactylus Gray,
      1827) belonging to the C. sworderi complex from a threatened karst forest in
      Perak, Peninsular Malaysia.
AB  - A new species of Bent-toed Gecko Cyrtodactylus guakanthanensis sp. nov. of the C.
      sworderi complex is described from a limestone forest in Perak, Peninsular
      Malaysia whose karst formations at the type locality are within an active quarry.
      Cyrtodactylus guakanthanensis sp. nov. can be distinguished from all other
      Sundaland species by having the following suite of character states: adult SVL
      77.7-82.2 mm; moderately sized, conical, weakly keeled, body tubercles; tubercles
      present on occiput, nape, and limbs, and extend posteriorly beyond base of tail;
      37-44 ventral scales; no transversely enlarged, median, subcaudal scales;
      proximal subdigital lamellae transversely expanded; 19-21 subdigital lamellae on
      fourth toe; abrupt transition between posterior and ventral femoral scales;
      enlarged femoral scales; no femoral or precloacal pores; precloacal groove
      absent; wide, dark postorbital stripes from each eye extending posteriorly to the
      anterior margin of the shoulder region thence forming a transverse band across
      the anterior margin of the shoulder region; and body bearing five (rarely four)
      wide, bold, dark bands. Destruction of the karst microhabitat and surrounding
      limestone forest will extirpate this new species from the type locality and
      perhaps drive it to complete extinction given that it appears to be restricted to
      the particular microhabitat structure of the type locality and is not widely
      distributed throughout the karst formations. As with plants and invertebrates,
      limestone forests are proving to be significant areas of high herpetological
      endemism and should be afforded special conservation status rather than turned
      into cement. 

PMID- 24869832
TI  - A new species of insular Rock Gecko (Genus Cnemaspis Strauch, 1887) from the
      Bidong Archipelago, Terengganu, Peninsular Malaysia.
AB  - A new insular species Cnemaspis bidongensis sp. nov. (Squamata: Gekkonidae), is
      described from Pulau Bidong, Terengganu, Peninsular Malaysia and bears a unique
      suite of morphological and color pattern characters that differentiate it from
      all other congeners. Cnemaspis bidongensis sp. nov. is the sister species to C.
      kendallii (Gray) and represents the fifth insular endemic species of Cnemaspis on
      archipelagos along the east coast of Peninsular Malaysia. This species survived
      massive deforestation of the small island of Bidong (260 ha) from the mid 1970s
      to the early 1990s when the island served as a Vietnamese refugee camp and
      harbored as many as 40,000 people at one time. We hypothesize that this species'
      generalized lifestyle contributed to its survival, allowing it to seek refuge in
      rocky microhabitats. 

PMID- 24869833
TI  - A review of Drilini (Coleoptera: Elateridae: Agrypninae) of the Northern Levant,
      with description of a new species from Syria and a key to Levantine species.
AB  - The species of the elaterid soft-bodied tribe Drilini from the Levant are
      reviewed. All known species are redescribed and Drilus nemethi sp. nov. is
      described. Drilus adustus (Chevrolat, 1854), comb. nov. and D. akbesianus
      (Fairmaire, 1895), comb. nov. are transferred from Malacogaster Bassi, 1834 to
      Drilus Olivier, 1790. Drilus posticus Schaufuss, 1867, syn. nov. is a junior
      subjective synonym of Drilus adustus (Chevrolat, 1854). All Levantine species are
      keyed and diagnostic characters are illustrated. Their distribution,
      morphological diversity and the statuses of type specimens of Drilus reitteri
      Bourgeois, 1908 and Cydistus reitteri Bourgeois, 1885 are discussed. 

PMID- 24869834
TI  - A new species of Bilyjomyia Niitsuma et Watson from Japan, with keys to species
      of the genus (Diptera: Chironomidae).
AB  - Descriptions of the male, female imagos, pupa and larva are given for Bilyjomyia
      parallela n. sp. collected from Japan. This is the third known species belonging
      to the genus Bilyjomyia. Keys to species of the genus are provided. 

PMID- 24869835
TI  - DNA barcoding assessment of genetic variation in two widespread skinks from
      Madagascar, Trachylepis elegans and T. gravenhorstii (Squamata: Scincidae).
AB  - Trachylepis elegans and T. gravenhorstii are two of the most widespread reptiles
      in Madagascar, inhabiting a wide variety of habitats. Previous studies have
      indicated a considerable mitochondrial DNA (mtDNA) variation within these
      species, but the geographic distribution of the major haplotype lineages is
      poorly known. Herein we analyse the phylogeography of these lizards based on 107
      sequences of the mitochondrial cytochrome oxidase subunit I gene, 101 of which
      newly determined. As in previous mtDNA assessments, T. elegans and T.
      gravenhorstii were not reciprocally monophyletic, although recent analyses
      including nuclear markers indicated their probable monophyly, respectively. The
      main lineages within T. gravenhorstii were found in strict allopatry and could be
      divided into a subclade of roughly northern and eastern distribution (lineages 1
      and 2) and a subclade of roughly southern and western distribution (lineages 3,
      4a, 4b, and 5, plus T. elegans). Our data serve to identify more precisely the
      probable contact zones among T. gravenhorstii lineages. The two main mtDNA clades
      (represented by lineages 2 and 3, respectively) can be expected to come into
      close contact in the area of the upper Mangoro river and Alaotra Lake, and
      (lineages 2 and 4a) in the Southern Central East between Mananjary and
      Ranomafana. Future studies intensively sampling these contact zones have the
      potential to assess hybridization and admixture among these lineages, and to test
      whether they are deep conspecific lineages of T. gravenhorstii as currently
      understood, or might represent distinct species. 

PMID- 24869836
TI  - Sexual morphs and biology of Aphis verbasci Schrank (Hemiptera: Aphididae).
AB  - The oviparous female and wingless male of Aphis verbasci from Poland and the
      United Kingdom are described and illustrated in detail for the first time, with
      notes on biology, distribution and host plants.  

PMID- 24869837
TI  - Gymnoxenisthmus tigrellus, new genus and species of gobioid fish from the Red Sea
      (Gobioidei: Xenisthmidae).
AB  - Gymnoxenisthmus tigrellus is described from the 15.2 mm SL holotype collected
      from the Farasan Archipelago, southern Red Sea. It is distinguished from other
      xenisthmid genera in having the following combination of characters: head pores
      absent; no scales; first dorsal fin with five spines; at least some dorsal-, anal
      and pectoral-fin rays branched; pelvic fin with a spine and five unbranched
      rays. Evaluation of available (mostly external) characters suggests the new genus
      is the sister group of a clade consisting of Rotuma, Tyson and Allomicrodesmus. 

PMID- 24869838
TI  - A new species of the leafhopper genus Multiformis Li & Li (Hemiptera:
      Cicadellidae: Evacanthinae) from China.
AB  - The species of the Oriental leafhopper genus Multiformis Li & Li are reviewed. A
      new species, Multiformis ramosus sp. nov., from Yunnan Province, China is
      described and a key to all known species of Multiformis is provided. 

PMID- 24869839
TI  - Revision of the checkered beetle genus Erymanthus Spinola, 1841 (Coleoptera,
      Cleridae, Clerinae).
AB  - The  genus  Erymanthus  Spinola,  1841  is  taxonomically  revised  to  include 
      sixteen  species.  The species E. transversopustulatus n. sp. is described as
      new. Erymanthus concoloripennis Pic, 1932, n. syn. is placed in synonymy with E.
      bicolor Chapin, 1924, E. horridus var. semirufus Kuwert, 1893 is recognized as a
      distinct and valid species E. semirufus; E. variegatus Pic, 1950 n. syn. is
      synonymized with E. pustulosus Quedenfeldt, 1888. A key to the species, color
      photographs, genital figures and distribution maps are provided. Erymanthus
      ampliatus Hintz, 1902 is transferred to the genus Gyponyx Gorham, 1883 (= Gyponyx
      amplicatus (Hintz, 1902) n. comb.). 

PMID- 24869840
TI  - Updated list and community structure of Tettigonioidea and Acridoidea (Insecta:
      Orthoptera) of the Alta Murgia plateau (Italy).
AB  - Alta Murgia calcareous plateau (southeast Italy) is thought to represent one of
      the most important area for Orthoptera in southern Italy, both due to its
      biogeographical concern and its unique richness in semi-natural dry grasslands.
      Since the half of the last century, no recent synthesis has been proposed for the
      Orthopterofauna of this area and a revision of old observations was still needed.
      This paper propose a reviewed list of Tettigonioidea and Acridoidea species from
      the Alta Murgia plateau, also providing information on local community structure
      and ecology. Based on the revision of previously published lists of species and
      on data collected during recent field works, a number of 37 species of
      grasshoppers and katydids is reported. The majority of species found in
      literature were confirmed, and six species were recorded as new for the area.
      Data collected during recent field works also enable to provide information about
      community structure, with particular focus on grassland habitat. This study also
      gives suggestions for replicable monitoring of Orthoptera assemblages in this
      area, as it is a valuable information for habitat surveillance purposes and
      ecosystem conservation strategies. 

PMID- 24869841
TI  - A new genus and new bromelicolous species of Cicadellini (Insecta: Hemiptera:
      Cicadellidae) from Southeastern Brazil.
AB  - A new genus, Cavichiana, is described for a new species of Cicadellini, C.
      bromelicola, from Southeastern Brazil (states of Rio de Janeiro and Sao Paulo).
      The new genus can be distinguished from other genera of the Cicadellini by the
      following combination of features: (1) head deltoid, strongly produced
      anteriorly; (2) ocelli located distinctly anterad of anterior eye angles; (3)
      aedeagus tubular, elongate, its apex with a conspicuous crown of spines; (4)
      paraphyses with both stalk and rami elongate, rami slender and each with
      basidorsal dentiform projection. The new species has a distinctive color pattern.
      The dorsum is dark brown to black with contrasting blue to white spots. The
      anterior half of the fore wings has a large, circular transcommissural yellow
      macula bordered by a blue to white border, the anterior portion of this macula
      covering the scutellum. Specimens of the new species were found on leaves of
      bromeliads in areas of restinga (sand dune vegetation) of the Atlantic Forest of
      Southeastern Brazil. Other cases of association between hemipterans and
      bromeliads are listed and briefly discussed. 

PMID- 24869842
TI  - Cyrtodactylus samroiyot, a new limestone-dwelling Bent-toed Gecko (Squamata:
      Gekkonidae) from Prachuap Khiri Khan Province, peninsular Thailand.
AB  - We describe Cyrtodactylus samroiyot sp. nov. from a limestone relief in Sam Roi
      Yot District, Prachuap Khiri Khan Province, peninsular Thailand. It is
      characterized by a maximal known SVL of 66.9 mm; 17-18 longitudinal rows of
      dorsal tubercles; 33-34 longitudinal rows of ventrals across the abdomen between
      the ventrolateral skin folds; a continuous series of seven precloacal pores in
      males (six shallow precloacal pits in females); a series of slightly enlarged,
      poreless and pitless femoral scales; no precloacal groove nor depression; median
      row of transversely enlarged subcaudal scales; a complete nuchal loop; and a
      dorsal pattern consisting of three long dark brown bands, one above shoulders and
      two above abdomen.  

PMID- 24869843
TI  - Cyrtodactylus khelangensis, a new cave-dwelling Bent-toed Gecko (Squamata:
      Gekkonidae) from Lampang Province, northern Thailand.
AB  - We describe Cyrtodactylus khelangensis sp. nov. from a limestone cave in Pratu
      Pha, Mae Mo District, Lampang Province, northern Thailand. It is characterized by
      a maximal known SVL of 95.3 mm; 16-20 longitudinal rows of dorsal tubercles; a
      continuous series of 37-40 enlarged femoroprecloacal scales, including six-seven
      pitted or pore-bearing scales (males) or one or two pitted scales (females) on
      each femur separated by a diastema from 2-6 pore-bearing precloacal scales (males
      and females); no precloacal groove nor depression; transversely enlarged
      subcaudal scales; and four irregular brown dorsal bands between nuchal loop and
      hind limb insertions. 

PMID- 24869844
TI  - New generic synonyms in the Palaeotropical genus Urothrips (Thysanoptera:
      Phlaeothripinae) with one new species from Seychelles.
AB  - Urothrips kobroi sp. n. is described from Seychelles, and reasons are given for
      considering Biconothrips Stannard and Coxothrips Bournier as new synonyms of
      Urothrips Bagnall. This genus now includes nine species, distributed between
      Africa and Australia, and a key to these species is provided. 

PMID- 24869845
TI  - Allopachria longyanensis sp. n. from China (Coleoptera: Dytiscidae).

PMID- 24869846
TI  - War traumas in the Mediterranean area.
AB  - INTRODUCTION: The purpose is to explore the consequences of war and its impact on
      mental health with attention to the Mediterranean area. METHODS: Narrative review
      of consequences of war on mental health and on the mental health of the
      communities in the current crises in the Mediterranean region. RESULTS: A series
      of outbreaks of war are still raging in the Mediterranean region and producing
      horrible effects with a considerable number of refugees with unsatisfied needs.
      Studies relating to conflicts of the past suggest that the mental health
      consequences of these wars may affect future generations for many years. While
      violations of human rights are not new, what is new are attacks on medical
      institutions perceived to be traditionally Western. CONCLUSION: The scientific
      community has to fight violence through mediation of conflicts. The idea that
      science can improve lives is a concept that is found in the history of all
      Mediterranean cultures. The Greek and Roman medical tradition was saved thanks to
      doctors of the Arab courts when Christian fundamentalism fought science in the
      Middle Ages. Health institutions are the product of the great Islamic medical
      tradition as well as Western culture.

PMID- 24869847
TI  - Mental health interventions for traumatized asylum seekers and refugees: What do
      we know about their efficacy?
AB  - BACKGROUND: The prevalence of trauma-related problems among refugees and asylum
      seekers is extremely high due to adverse experiences associated with forced
      migration. Although the literature presents a considerable number of guidelines
      and theoretical frameworks for working with traumatized refugees and asylum
      seekers, the efficacy, feasibility and applicability of these interventions have
      little empirical evidence. AIMS: The purpose of this article is to critically
      review the literature to provide a rationale for developing culturally sensitive,
      evidence-based interventions for refugees and asylum seekers. METHODS: A
      literature review integrating research findings on interventions designed
      especially for traumatized asylum seekers and refugees was conducted. Retained
      studies had to use some quantitative measurements of post-traumatic stress and to
      have pre- and post-measurements to evaluate the efficacy of the intervention.
      Studies included in this review cover a wide variety of interventions, including
      trauma-focused interventions, group therapy, multidisciplinary interventions and
      pharmacological treatments. RESULTS: The majority of studies with traumatized
      refugees and asylum seekers reported positive outcomes of the intervention in
      reducing trauma-related symptoms. There is evidence to support the suitability of
      cognitive-behavioral therapy (CBT) and narrative exposure therapy (NET) in
      certain populations of refugees. Other intervention studies are limited by
      methodological considerations, such as lack of randomization, absence of control
      group and small samples. CONCLUSIONS: This review has again highlighted the
      shortage of guiding frameworks available to investigators and clinicians who are
      interested in tailoring interventions to work with refugees and asylum seekers.
      Theoretical, ethical and methodological considerations for future research are
      discussed.

PMID- 24869849
TI  - 'We didn't have a clue': Family caregivers' experiences of the communication of a
      diagnosis of schizophrenia.
AB  - BACKGROUND: Despite widespread acceptance of the principle that patients should
      be informed about their diagnosis, many clinicians are reluctant to provide a
      diagnosis of schizophrenia. This study examines family caregivers' experiences of
      the communication of a schizophrenia diagnosis and related information. METHODS:
      A generic qualitative methodological approach was used. In all, 13 family
      caregivers were recruited in regional New South Wales, Australia. Semi-structured
      interviews were used to explore their experiences and perceptions of discussing
      the diagnosis, prognosis and treatment of schizophrenia with mental health
      professionals. Interviews were recorded, transcribed, codes generated and
      thematic analysis undertaken. RESULTS: Family caregivers described long and
      difficult pathways to being given a diagnosis, haphazard means of finding out the
      diagnosis, high unmet needs for information, exclusion from the medical care
      process and problematic communication and general interactions with mental health
      clinicians. Caregivers were unanimous about the importance of receiving a timely
      diagnosis, for them and their relative with schizophrenia. CONCLUSION: Family
      caregivers are an integral part of the mental health-care system, and they should
      be included early in discussions of diagnosis and treatment of a person with
      schizophrenia. Their perspectives on communicating a diagnosis of schizophrenia
      provide important information for communication skills training of psychiatrists
      and other mental health professionals.

PMID- 24869850
TI  - Patterns of non-suicidal self-injurious behaviours among college students in
      India.
AB  - BACKGROUND: Non-suicidal self-injurious behaviour (NSSI) is a growing concern
      among youth and rarely reaches the attention of mental health and medical
      services. AIMS: The study explored the occurrence, methods, characteristics and
      reported reasons for NSSI among a sample of college students in India. METHODS: A
      total of 470 participants from undergraduate and postgraduate colleges completed
      the Functional Assessment of Self Mutilation (FASM) questionnaire. RESULTS:
      Results indicated that 31.2% of the participants reported NSSI in the past year,
      with the mean age of onset being 15.9 years. Moderate/severe forms of NSSI were
      reported by 19.8% of the sample. The most common method was self-hitting (15.2%)
      followed by cutting or carving skin (13.2%). A majority of self-injurers endorsed
      multiple methods of NSSI, and there were no significant gender differences in
      NSSI rates. The NSSI was performed both to regulate internal emotional states
      (automatic reinforcement) and to influence others in the environment (social
      reinforcement).The most commonly endorsed reasons for NSSI were 'to feel relaxed'
      and 'to get control of the situation', while the least frequently endorsed
      reasons were 'to make others angry' and 'to avoid college, work, or other
      activities'. CONCLUSION: The findings underscore the need to increase the
      awareness and understanding of NSSIs and to plan targeted interventions among
      college youth.

PMID- 24869851
TI  - Logistic regression analysis of psychosocial correlates associated with recovery
      from schizophrenia in a Chinese community.
AB  - BACKGROUND AND AIMS: More mental health services are adopting the recovery
      paradigm. This study adds to prior research by (a) using measures of stages of
      recovery and elements of recovery that were designed and validated in a non
      Western, Chinese culture and (b) testing which demographic factors predict
      advanced recovery and whether placing importance on certain elements predicts
      advanced recovery. METHOD: We examined recovery and factors associated with
      recovery among 75 Hong Kong adults who were diagnosed with schizophrenia and
      assessed to be in clinical remission. Data were collected on socio-demographic
      factors, recovery stages and elements associated with recovery. Logistic
      regression analysis was used to identify variables that could best predict stages
      of recovery. Receiver operating characteristic curves were used to detect the
      classification accuracy of the model (i.e. rates of correct classification of
      stages of recovery). RESULTS: Logistic regression results indicated that stages
      of recovery could be distinguished with reasonable accuracy for Stage 3 ('living
      with disability', classification accuracy = 75.45%) and Stage 4 ('living beyond
      disability', classification accuracy = 75.50%). However, there was no sufficient
      information to predict Combined Stages 1 and 2 ('overwhelmed by disability' and
      'struggling with disability'). It was found that having a meaningful role and age
      were the most important differentiators of recovery stage. CONCLUSION:
      Preliminary findings suggest that adopting salient life roles personally is
      important to recovery and that this component should be incorporated into mental
      health services.

PMID- 24869848
TI  - Identification of the hikikomori syndrome of social withdrawal: Psychosocial
      features and treatment preferences in four countries.
AB  - BACKGROUND: Hikikomori, a form of social withdrawal first reported in Japan, may
      exist globally but cross-national studies of cases of hikikomori are lacking.
      AIMS: To identify individuals with hikikomori in multiple countries and describe
      features of the condition. METHOD: Participants were recruited from sites in
      India, Japan, Korea and the United States. Hikikomori was defined as a 6-month or
      longer period of spending almost all time at home and avoiding social situations
      and social relationships, associated with significant distress/impairment.
      Additional measures included the University of California, Los Angeles (UCLA)
      Loneliness Scale, Lubben Social Network Scale (LSNS-6), Sheehan Disability Scale
      (SDS) and modified Cornell Treatment Preferences Index. RESULTS: A total of 36
      participants with hikikomori were identified, with cases detected in all four
      countries. These individuals had high levels of loneliness (UCLA Loneliness Scale
      M = 55.4, SD = 10.5), limited social networks (LSNS-6 M = 9.7, SD = 5.5) and
      moderate functional impairment (SDS M = 16.5, SD = 7.9). Of them 28 (78%) desired
      treatment for their social withdrawal, with a significantly higher preference for
      psychotherapy over pharmacotherapy, in-person over telepsychiatry treatment and
      mental health specialists over primary care providers. Across countries,
      participants with hikikomori had similar generally treatment preferences and
      psychosocial features. CONCLUSION: Hikikomori exists cross-nationally and can be
      assessed with a standardized assessment tool. Individuals with hikikomori have
      substantial psychosocial impairment and disability, and some may desire
      treatment.

PMID- 24869852
TI  - Depictions of auditory verbal hallucinations in news media.
AB  - BACKGROUND: The characterization of auditory verbal hallucinations (AVH) in the
      Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V),
      diverges from recent research literature, which demonstrates the occurrence of
      AVH in individuals who are psychologically healthy. This discrepancy raises the
      question of how the public perceives AVH. Public perceptions are important
      because they could potentially affect how individuals with AVH interpret these
      experiences and how people view voice hearers. AIMS: Because media portrayals can
      provide a window into how phenomena are viewed by the public, an archival study
      of newspaper articles was carried out to examine depictions of AVH. METHODS: A
      sample of 181 newspaper articles originating in the United States was analyzed
      using a content analysis approach. RESULTS: The majority of articles examined
      contained no suggestion that AVH are possible in psychologically healthy
      individuals. Most articles suggested that AVH were a symptom of mental illness,
      and many suggested that AVH were associated with criminal behavior, violence and
      suicidality. CONCLUSION: The news media examined tended to present a misleading
      and largely pathologizing view of AVH. More research is needed to shed light on
      how, and to what extent, public perceptions may influence those who experience
      AVH.

PMID- 24869855
TI  - Establishing homology between mitochondrial calcium uniporters, prokaryotic
      magnesium channels and chlamydial IncA proteins.
AB  - Mitochondrial calcium uniporters (MCUs) (TC no. 1.A.77) are oligomeric channel
      proteins found in the mitochondrial inner membrane. MCUs have two well-conserved
      transmembrane segments (TMSs), connected by a linker, similar to bacterial MCU
      homologues. These proteins and chlamydial IncA proteins (of unknown function; TC
      no. 9.B.159) are homologous to prokaryotic Mg(2+) transporters, AtpI and AtpZ,
      based on comparison scores of up to 14.5 sds. A phylogenetic tree containing all
      of these proteins showed that the AtpZ proteins cluster coherently as a subset
      within the large and diverse AtpI cluster, which branches separately from the
      MCUs and IncAs, both of which cluster coherently. The MCUs and AtpZs share the
      same two TMS topology, but the AtpIs have four TMSs, and IncAs can have either
      two (most frequent) or four (less frequent) TMSs. Binary alignments, comparison
      scores and motif analyses showed that TMSs 1 and 2 align with TMSs 3 and 4 of the
      AtpIs, suggesting that the four TMS AtpI proteins arose via an intragenic
      duplication event. These findings establish an evolutionary link interconnecting
      eukaryotic and prokaryotic Ca(2+) and Mg(2+) transporters with chlamydial IncAs,
      and lead us to suggest that all members of the MCU superfamily, including IncAs,
      function as divalent cation channels. 

PMID- 24869857
TI  - Effects of pulsed electromagnetic fields on the expression of NFATc1 and CAII in
      mouse osteoclast-like cells.
AB  - BACKGROUND AND AIMS: Pulsed electromagnetic fields (PEMF) have proven to be an
      effective noninvasive method in the prevention and treatment of osteoporosis.
      This study evaluated the effects of PEMF on the expression of the NFATc1, CAII
      and RANK genes in mouse osteoclast-like cells. METHODS: Bone marrow from
      bilateral tibiae and femurs was cultured in differentiation medium in the
      presence of soluble macrophage colony stimulating factor (M-CSF) and receptor
      activator of nuclear factor kappa-B ligand (RANKL). After 5 days, the osteoclast
      like cells were confirmed by both tartrate-resistant acid phosphatase (TRAP)
      staining and bone resorption assays. The osteoclast-like cells were divided into
      five groups and exposed to the following treatments for 3 days: M-CSF; M-CSF +
      RANKL; M-CSF + RANKL + osteoprotegerin (OPG), M-CSF + RANKL + premarin (E2); and
      M-CSF + RANKL + PEMF. The numbers of multinucleated, TRAP-positive osteoclast
      like cells and resorption pits formed were determined. The expression of NFATc1,
      CAII and RANK mRNA was determined with real-time fluorescent quantitative
      polymerase chain reaction. RESULTS: PEMF substantially reduced the number of
      osteoclast-like cells in the culture with M-CSF + RANKL. The level of NFATc1,
      CAII, and RANK mRNA expression was decreased in the M-CSF + RANKL + PEMF group
      compared to the M-CSF + RANKL group (p = 0.007, p = 0.039, p = 0.001,
      respectively). The mRNA expression of NFATc1, CAII, and RANK was not higher in
      the M-CSF + RANKL + OPG group compared to the M-CSF + RANKL + PEMF group (p =
      0.682, p = 0.200, p = 0.924, respectively). In addition, there was no difference
      in the expression of mRNA from NFATc1, CAII, and RANK between the M-CSF + RANKL +
      PEMF group and the M-CSF + RANKL + E2 group (p = 0.853, p = 0.509, p = 0.664,
      respectively). CONCLUSIONS: These data suggest that PEMF might modulate the
      process of osteoclastogenesis and subsequent bone resorption, at least partially,
      through NFATc1, CAII and RANK.

PMID- 24869858
TI  - Early recognition of acquired hemophilia in elderly: case report of two
      consecutive patients.

PMID- 24869856
TI  - Extensive expansion of A1 family aspartic proteinases in fungi revealed by
      evolutionary analyses of 107 complete eukaryotic proteomes.
AB  - The A1 family of eukaryotic aspartic proteinases (APs) forms one of the 16 AP
      families. Although one of the best characterized families, the recent increase in
      genome sequence data has revealed many fungal AP homologs with novel sequence
      characteristics. This study was performed to explore the fungal AP sequence space
      and to obtain an in-depth understanding of fungal AP evolution. Using a
      comprehensive phylogeny of approximately 700 AP sequences from the complete
      proteomes of 87 fungi and 20 nonfungal eukaryotes, 11 major clades of APs were
      defined of which clade I largely corresponds to the A1A subfamily of pepsin
      archetype APs. Clade II largely corresponds to the A1B subfamily of nepenthesin
      archetype APs. Remarkably, the nine other clades contain only fungal APs, thus
      indicating that fungal APs have undergone a large sequence diversification. The
      topology of the tree indicates that fungal APs have been subject to both "birth
      and death" evolution and "functional redundancy and diversification." This is
      substantiated by coclustering of certain functional sequence characteristics. A
      meta-analysis toward the identification of Cluster Determining Positions (CDPs)
      was performed in order to investigate the structural and biochemical basis for
      diversification. Seven CDPs contribute to the secondary structure of the enzyme.
      Three other CDPs are found in the vicinity of the substrate binding cleft. Tree
      topology, the large sequence variation among fungal APs, and the apparent
      functional diversification suggest that an amendment to update the current A1 AP
      classification based on a comprehensive phylogenetic clustering might contribute
      to refinement of the classification in the MEROPS peptidase database. 

PMID- 24869859
TI  - A taxonomic review of the wolf spider genus Agalenocosa Mello-Leitao (Araneae,
      Lycosidae).
AB  - The lycosid genus Agalenocosa Mello-Leitao, 1944 comprises at least eight species
      from northern and eastern Argentina and neighbouring countries: Agalenocosa velox
      (Keyserling, 1891) comb. nov. (from southern Brazil and Argentina), transferred
      here from Pirata Sundevall, 1833, A. tricuspidata (Tullgren, 1905) comb. nov.
      (from northwestern Argentina), transferred here from Pardosa C.L. Koch, 1847, A.
      luteonigra (Mello-Leitao, 1945) (from Argentina and Uruguay), A. punctata Mello
      Leitao, 1944 (from Buenos Aires and Entre Rios, Argentina),  A. gentilis Mello
      Leitao, 1944 (from Buenos Aires, Argentina), and three new species: A. pirity sp.
      nov., A. gamas sp. nov. (from eastern Argentina), and A. grismadoi sp. nov. (from
      eastern Argentina and Paraguay). Agalenocosa singularis Mello-Leitao (type
      species of the genus) is considered a junior synonym of A. velox. Agalenocosa
      fimbriata Mello-Leitao, 1944 is considered species inquirenda; Agalenocosa
      bryantae (Roewer, 1951), A. chacoensis (Mello-Leitao, 1942), A. denisi
      (Caporiacco, 1947), A. kolbei (Dahl, 1908), A. melanotaenia (Mello-Leitao, 1941),
      A. pickeli (Mello-Leitao, 1937), A. yaucensis (Petrunkevitch, 1929), A. fallax
      (L. Koch, 1877), A. helvola (C. L. Koch, 1847), A. subinermis (Simon, 1897) are
      considered misplaced species. The subfamily placement of Agalenocosa is briefly
      discussed, and it could be placed in either Piratinae Zyuzin, 1993 or Venoniinae
      Lehtinen & Hippa, 1979.  

PMID- 24869860
TI  - Revision of Acrochordonoposthia Reisinger, 1924 (Rhabditophora, Typhloplanidae,
      Protoplanellinae) with the description of one new species.
AB  - An overview of the morphology, taxonomy and distribution of all known species of
      the rhabdocoel taxon Acrochordonoposthia is provided. One new species A.
      vandeputae n. sp. is described from Graz (Austria). This new species can easily
      be distinguished from its congeners by the morphology of its copulatory organ,
      which contains a straight cirrus lined with spines. All species of
      Acrochordonoposthia are compared with one another, and an updated identification
      key is provided. 

PMID- 24869861
TI  - The genus Clathria from the Gulf of Mexico and Mexican Caribbean, with
      redescription and resurrection of Clathria carteri (Poecilosclerida:
      Microcionidae).
AB  - The present study deals with the morphologic variability of eight Clathria
      species from the southern Gulf of Mexico and Mexican Caribbean. Clathria
      (Clathria) foliacea, C. (C.) carteri, C. (Microciona) calla, C. (M.) echinata, C.
      (M.) spinosa, C. (Thalysias.) venosa, and C. (T.) virgultosa were collected by
      scuba diving and dredging from the southern Gulf of Mexico (Veracruz, Campeche
      Bank, Yucatan) to the Caribbean coast (Quintana Roo) from shoreline to 120 m
      depth. The population of Clathria seems to be neither abundant nor diverse in the
      studied area. However, the seven species considered here are presumed to have a
      slight morphologic variability, and the interspecific relationships had not been
      fully resolved. The present study focuses on their differentiation through
      comparison of external morphology, skeletal architecture, spiculation and
      measurements of characters as well as scanning electronic microscopy.   
      Comparisons were made among intra- and interspecific material and with the
      available type material. In particular, C. carteri Topsent (1889), previously
      synonymized with C. foliacea, is resurrected by establishing a neotype from
      material from the type locality, Campeche Bank; this has not been studied since
      its original description and is here redescribed for the first time. Another
      neotype is assigned for C. foliacea from Campeche also, since the original
      material is no longer available, and this species is redescribed also.
      Significant differences in spiculation between C. foliacea and C. carteri were
      found by one-way ANOVA. Although C. (T.) venosa resembles C. (T.) raraechelae in
      spiculation, these two species differ in measurements and skeletal organization.
      C. (T.) virgultosa is typified by a peculiar acanthostyle that is markedly spined
      on distal parts of the shaft, and by two types of tiny microscleres. This study
      has extended the known geographic distribution of each of these Clathria spp.
      within the lower Gulf of Mexico. 

PMID- 24869862
TI  - Taxonomic assessment of Chirosiomima Hennig (Diptera: Anthomyiidae), with
      proposal of a new genus for Hylemyia curtigena Ringdahl.
AB  - The four nominal species currently included in the anthomyiid genus Chirosiomima
      Hennig, 1966 are critically assessed and redescribed. It is shown that the type
      species of Chirosiomima was originally misidentified. Chirosiomima obscurinervis
      (Emden, 1941) is resurrected from synonymy of C. gestroi (Seguy, 1930).
      Chirosiomima collini Ackland, 1968 is transferred to Botanophila Lioy (comb.
      nov.) and C. curtigena (Ringdahl, 1935) to Ringdahlia gen. nov. (comb. nov.). The
      previously unknown male of C. gestroi and female of R. curtigena (Ringdahl) are
      described. 

PMID- 24869863
TI  - The type specimens of sawflies (Hymenoptera: Symphyta) of the Museo Nacional de
      Ciencias Naturales, Madrid.
AB  - The type specimens of sawflies (Hymenoptera: Symphyta) housed in the Museo
      Nacional de Ciencias Naturales, Madrid, were examined. Lectotypes are designated
      and illustrated for the following 32 nominal taxa (preserved in the MNCN
      collection if not stated otherwise): Tenthredo acutiscutis Konow, 1908; Tenthredo
      aericeps Konow, 1907; Allantus albipectus Konow, 1907; Athalia bolivari Dusmet,
      1896; Tristactus punctatus var. candidatus Konow, 1899; Tenthredo capistrata
      Konow, 1907; Megalodontes capitalatus Konow 1904 (coll. SDEI); Tenthredo casta
      Konow, 1908; Clydostomus cestatus Konow, 1908; Miocephala chalybea Konow, 1907
      (coll. SDEI); Peus cupreiceps Konow, 1907; Metallopeus cupreolus Malaise, 1945
      (coll. NHRS); Allantus dusmeti Konow, 1894 (coll. SDEI); Megalodontes dusmeti
      Enslin, 1914 (coll. ZSM); Megalodontes escalerai Konow, 1899; Tenthredo
      flavitarsis Konow, 1908; Sciopteryx galerita Konow, 1907; Tenthredo habenata
      Konow, 1907; Allantus inguinalis Konow, 1908; Clydostomus merceti Konow, 1908;
      Megalodontes merceti Konow 1904 (coll. SDEI); Tenthredo mordax Konow, 1908;
      Megalodontes mundus Konow, 1904; Tenthredo nimbata Konow, 1906; Tenthredo
      oculissima Konow, 1907; Peus pannulosus Konow, 1907; Tenthredo podagrica Konow,
      1907; Arge segmentaria var. rufiventris Konow, 1899; Tenthredo rugiceps Konow,
      1908; Tenthredo segrega Konow, 1908; Peus splendidus Konow 1907; Tenthredo suta
      Konow, 1906. Peus cupreiceps Konow, 1907, is considered to be a valid species.
      New synonymy is proposed for Tenthredo (Metallopeus) cupreiceps (Konow, 1907),
      comb. nov., spec. rev. (=Metallopeus cupreolus Malaise, 1945, syn. nov.;
      =Metallopeus inermis Malaise, 1945, syn. nov.).  

PMID- 24869864
TI  - Taxonomy of fungus gnats allied to Neoempheria ferruginea (Brunetti, 1912)
      (Diptera: Mycetophilidae), with descriptions of 11 new species from Japan and
      adjacent areas.
AB  - Specimens of Neoempheria previously considered to be N. ferruginea (Brunetti,
      1912) are studied and revised. Eleven new species are described from Japan,
      Nepal, Philippines, and Thailand; N. biceltisuta sp. n., N. bifurcata sp. n., N.
      bisecuriata sp. n., N. brevispathulata sp. n., N. carinata sp. n., N. cuneata sp.
      n., N. dilatata sp. n., N. denticulata sp. n., N. forficulata sp. n., N.
      latisternata sp. n., and N. muticata sp. n. Neoempheria sakhalinensis Zaitzev,
      2001, is recorded from Japan for the first time. Male genitalia of these 12
      species are illustrated. A key to the species is provided. A lectotype of Mycomya
      ferruginea Brunetti, 1912 is designated (deposited in the Zoological Survey of
      India, Kolkata) and the species redescribed. Morphological similarities and
      differences among N. ferruginea and allied species are discussed. The usefulness
      of the male gonocoxite and associated structures, and the gonapophysis of the
      female 8th and 9th abdominal sternites for taxonomy are discussed.  

PMID- 24869865
TI  - Rhodeus albomarginatus, a new bitterling (Teleostei: Cyprinidae:
      Acheilognathinae) from China.
AB  - Rhodeus albomarginatus, new species, is described from the Lvjiang River, a
      tributary flowing into Poyang Lake of Yangtze River basin, in Anhui Province,
      China. It is distinguished from all congeneric species by unique combination of
      characters: branched dorsal-fin rays 10; branched anal-fin rays 10-11; longest
      simple rays of dorsal and anal fins strong and stiff, distally segmented; pelvic
      fin rays i 6; longitudinal scale series 34-36; transverse scale series 11; pored
      scales 4-7; vertebrae 33-34; colour pattern of adult males (iris black, belly
      reddish-orange, central part of caudal fin red, dorsal and anal fins of males
      edged with white margin). 

PMID- 24869866
TI  - Agaporomorphus sharynae, a new species of diving beetle (Coleoptera: Dytiscidae:
      Copelatinae) from Venezuela.
AB  - Agaporomorphus sharynae sp. n. is described from Amazonas, Venezuela.
      Agaporomorphus Zimmermann, 1921 now includes nine known species. The new species
      is part of the A. knishi species group since it has similarly convoluted male
      genitalia with rows of setae on the dorsal surface. Males can be separated from
      those of other members of the genus by the structure of the abdominal ventrites,
      shape of the antennae, and shape of the male median lobe. The cladistic analysis
      of K.B. Miller & Wheeler (2008) is modified to include the new species. The
      habitus and male and female genitalia are illustrated, and male genitalia of
      other species of the A. knishi species group are illustrated for comparison. 

PMID- 24869867
TI  - A new species of Atanatolica Mosely 1936 (Trichoptera: Leptoceridae) from Serra
      Bonita, Bahia, Brazil.
AB  - The Neotropical genus Atanatolica includes 17 species distributed from Costa Rica
      to Brazil, but only two, A. brasiliana and A. flinti, have been recorded from
      Brazil, both occurring in Rio de Janeiro and Sao Paulo States. A new species,
      Atanatolica bonita n. sp., is described and illustrated based on males and
      females from the Atlantic Forest in Bahia State in northeastern Brazil. The new
      species can be diagnosed by the following characters: Apicomesal and apicolateral
      processes of segment X of same length, long and digitate; and second article of
      each inferior appendage well developed, long, and thumb-shaped. Notes on
      demographic changes and correlations with seasonal variation and precipitation
      are also given. 

PMID- 24869868
TI  - Checklist of Braconinae species of Turkey (Hymenoptera: Braconidae).
AB  - The Braconinae (Hymenoptera: Braconidae) species recorded from Turkey are listed,
      the present total number being 195. Changes with respect to the previous Turkish
      fauna are briefly annotated and the distributions for all the species in each of
      the 68 biogeographical provinces are presented. After the publication of our
      previous fauna, 173 species have been recorded as new to Turkey. Of these, 96
      species are distributed only in Asian Turkey and 14 species are distributed only
      in European Turkey, while 85 species occure in both. The presented checklist
      covers synonyms, zoogeographical region(s), hosts, host plants of host species
      and parasitoid data for the species. In total, 195 species belonging 9 genera are
      reported for the studied regions of Turkey. The number of species of each genus
      is represented by: Atanycolus Foester, 1862: 4, Baryproctus Ashmead, 1900: 1,
      Bracon Fabricius, 1804: 149, Ceratobracon Telenga, 1936: 1, Coeloides
      Wesmael,1838: 2, Glyptomorpha Holmgren, 1868: 7, Iphiaulax Foerster, 1862: 9,
      Pseudovipio Szepligeti, 1896: 9, Vipio Latreille, 1804: 13 species. Bracon
      (Asiabracon) amaculatus Beyarslan, 1988 is synonymized with B. (A.)
      quadrimaculatus Telenga, 1936.  

PMID- 24869869
TI  - Revision of the Antarctic species of Halecium Oken, 1815 (Cnidaria, Hydrozoa,
      Haleciidae).
AB  - A revision of the known Antarctic species of the genus Halecium has been carried
      out, based on the study of both type and non-type material. For each species a
      list of synonyms, a diagnosis, a broad description (with the exception of the
      recently described H. frigidum and H. exaggeratum), a discussion of its
      relationship with other members of the genus, and an account of its autecological
      data are given. Thirteen Antarctic species of the genus, including H.
      pseudodelicatulum sp. nov. and H. pseudoincertus sp. nov., are considered valid.
      Halecium tubatum is considered as species inquirenda. Halecium ovatum and H.
      macrocaulus are considered to be junior synonyms of H. interpolatum and H.
      incertus, respectively. The presence of H. delicatulum and H. tenellum in
      Antarctic waters is questioned. All Antarctic records found in the literature
      have been checked. The cnidome proved to be a useful tool for species
      identification in some cases. Finally, a general survey of the geographical and
      bathymetric distribution of the species is presented. 

PMID- 24869870
TI  - A review of the natural history of adult Cetoniinae (Coleoptera: Scarabaeidae)
      from Argentina and adjacent countries.
AB  - A compilation of the known natural history of adult Cetoniinae (Coleoptera:
      Scarabaeidae) from Argentina and adjacent countries is provided. Food items of
      adult Cetoniinae include pollen and/or nectar (flower visitors), sap and/or slime
      flux, ripened fruits on plants, green tissues and leaves, and honey. Of the 36
      species of Cetoniinae from Argentina, food items are known only for 11 species
      (30.5%). Attraction to light and bait-traps, adult activity periods, vertebrate
      predators, and the occurrence in bird nests are presented and discussed. Other
      insects that share the same food sources and bait-traps with Cetoniinae are
      mentioned. 

PMID- 24869871
TI  - Cebrennus Simon, 1880 (Araneae: Sparassidae): a revisionary up-date with the
      description of four new species and an updated identification key for all
      species.
AB  - The spider genus Cebrennus Simon, 1880 is revised again after thirteen years.
      Four new species are described: Cebrennus atlas spec. nov. from Morocco (female),
      C. flagellatus spec. nov. from Afghanistan (male), C. laurae spec. nov. from
      Canary Islands (male), and C. rechenbergi spec. nov. from Morocco (male and
      female). Cebrennus clercki (Audouin, 1826) comb. nov. is transferred from
      Philodromidae to Sparassidae and considered a nomen dubium. The holotype of C.
      aethiopicus Simon, 1880 is illustrated for the first time. Cebrennus tunetanus
      Simon, 1885 is re-described by illustrating its copulatory organs and some
      somatic characters, the internal duct system is shown for the first time
      supporting its placement in Cebrennus. An updated identification key for all
      species is provided. New records of Cebrennus species are listed: C. wagae
      (Simon, 1874) is recorded from Libya and Malta for the first time, the latter
      representing the first record for the entire genus from Europe. C. kochi (O.
      Pickard-Cambridge, 1872) is recorded from Syria, C. aethiopicus from Sudan for
      the first time. Records from the Canary Islands and from Afghanistan extend the
      known generic distribution range further to the West and East. Behavioural
      aspects (burrowing, escaping, mating) of C. rechenbergi and partly of C. villosus
      (Jezequel & Junqua, 1966) are described. Photographs of this behaviour as well as
      of the habitus of several species are provided. 

PMID- 24869872
TI  - Tardigrades from Peru (South America), with descriptions of three new species of
      Parachela.
AB  - In four samples of mosses and mosses mixed with lichens collected in the Peruvian
      region of Cusco, 344 tardigrades, 78 free-laid eggs and six simplexes were found.
      In total, nine species were identified: Cornechiniscus lobatus, Echiniscus
      dariae, E. ollantaytamboensis, Isohypsibius condorcanquii sp. nov., Macrobiotus
      pisacensis sp. nov., Milnesium krzysztofi, Minibiotus intermedius,
      Paramacrobiotus intii sp. nov. and Pseudechiniscus ramazzottii ramazzottii.
      Isohypsibius condorcanquii sp. nov. is most similar to I. baldii, but differs
      mainly by the absence of ventral sculpture, the presence of the oral cavity
      armature, a different macroplacoid length sequence and a different shape of
      macroplacoids. The new species also differs from other congeners by a different
      dorsal sculpture, the absence of cuticular bars under the claws and the absence
      of eyes. Macrobiotus pisacensis sp. nov. differs from the most similar M.
      ariekammensis and M. kirghizicus by a different oral cavity armature, the
      presence of cuticular pores, details of egg morphology and some morphometric
      characters of both animals and eggs. Paramacrobiotus intii sp. nov. differs from
      most similar species of the genus by a different type of the oral cavity
      armature, details of egg morphology and some morphometric characters of both
      animals and eggs. In addition, we briefly discuss the tardigrade fauna of Peru,
      and propose a simple and economic system of describing relative lengths of
      pharyngeal macroplacoids. The system is especially useful in interspecific
      comparisons and differential diagnoses. 

PMID- 24869873
TI  - Description of immatures of the genus Tropisternus Solier, subgenus Pristoternus
      Orchymont (Coleoptera: Hydrophilidae), with emphasis on the chaetotaxy and
      morphometry of larval forms.
AB  - The egg cases, larvae, and pupae of Tropisternus (Pristoternus) latus (Brulle,
      1837), T. (P.) ovalis Castelnau, 1840, and T. (P.) laevis (Sturm, 1826) are
      illustrated and described for the first time. The egg cases are built with or
      without a mast, which can be ribbon-like or globular; all larval instars have
      seven anterior denticles in the anterior margin of nasale, and the antennal seta
      AN8 is present; the pupae bear 6 or 8 styli on the abdominal segments II-VI, the
      pleural styli can be either short or very long, and horn-like projections may be
      present on the abdominal segments II-VI. A comparison of the morphology of the
      egg cases, pupae and larval chaetotaxic and morphometric characters within the
      genus Tropisternus is presented. 

PMID- 24869874
TI  - Correction of the type species of the South American genus Gromphas Brulle, 1837
      (Coleoptera: Scarabaeidae: Scarabaeinae: Phanaeini).
AB  - Recently, we (Cupello & Vaz-de-Mello, 2013) presented a taxonomic revision of the
      dung beetle genus Gromphas Brulle, 1837 in which we recognized the validity of
      five species: Gromphas aeruginosa (Perty, 1830), G. amazonica Bates, 1870, G.
      dichroa Blanchard, 1846, G. inermis Harold, 1869, and G. lemoinei Waterhouse,
      1891. In that work, we also confirmed that Gromphas was described by Brulle
      (1837) without any included species and that the widely cited name "Gromphas
      lacordairei Brulle" was never formally described or cited by Brulle and, in fact,
      all citations to this name refer to G. lacordairii Burmeister, 1874, a junior
      synonym of G. inermis Harold, 1869. Thus, the question of the identity of the
      type species of Gromphas remained open.  

PMID- 24869875
TI  - Cryptic speciation of Greek populations of the freshwater shrimp genus Atyaephyra
      de Brito Capello, 1867 (Crustacea, Decapoda), evidence from mitochondrial DNA.
AB  - The freshwater shrimp genus Atyaephyra de Brito Capello, 1867 is a complex of
      cryptic species with morphologically overlapping features, which has led to
      invalid identifications until recently. The genus is distributed around the
      entire Mediterranean Basin and surrounding areas. In 2009 we used a molecular
      approach with 16S and Cox1 genes to identify the European and African populations
      and to show the existence of different species and groups of haplotypes (Garcia
      Munoz et al. 2009). Christodoulou et al. (2012) recently identified four species
      in Greece (Atyaephyra stankoi, A. thyamisensis, A. strymonensis and A.
      acheronensis) based on morphology and some partial sequences of Cox1. In the
      present study we analyse several Greek populations of Atyaephyra spp. using
      morphology and two mitochondrial markers (16S and Cox1). Our molecular data
      confirm the taxonomic validity of A. stankoi, A. thyamisensis and A. strymonensis
      but show that A. acheronensis should be considered a synonym of A. desmarestii.
      The limited distribution of A. desmarestii in only a few rivers in the Ionian
      region is probably the result of a posterior introduction from neighbouring
      European areas. After the genetic identification and as a consequence of the high
      variability observed within species and between rivers, mainly in A.
      thyamisensis, we re-describe this species and provide morphological data for the
      other species. We also give information on the chromatophore pattern in larvae,
      which could be very useful in the future for recognizing species and their
      distribution. The distribution of Greek Atyaephyra species seems to be related to
      the very complex paleogeographical history of the Paratethys and Mediterranean
      Sea in the Balkan Peninsula. Three areas can be recognized in relation to the
      distribution of these species: a global region, a western region separated from
      the eastern region by the Pindos Mountains, and a Macedonia-Thracian region.  

PMID- 24869876
TI  - Chalinochromis cyanophleps, a new species of cichlid fish (Teleostei: Cichlidae)
      from Lake Tanganyika.
AB  - Chalinochromis cyanophleps is described from nine specimens, the largest 129 mm
      SL, from Namansi. It differs from other species of Chalinochromis in plain trunk
      colouration, absence of black stripes on the head, relatively narrow lips,
      presence of tricuspid jaw teeth, and presence of five rather than four dentary
      lateralis foramina. The blue iridescent stripe below the eye is shared with other
      lamprologin cichlids, but is broader and more conspicuous in C. cyanophleps.
      Chalinochromis cyanophleps occurs at depths between 6 and 45 m in rocky habitats
      along the Tanzanian coast of Lake Tanganyika, from Mvuna Island south to Kalala
      Island, a stretch of about 90 km. Field observations were made of specimens up to
      18 cm total length. The COI DNA barcode sequence differs by 1.8% from that of C.
      popelini. 

PMID- 24869877
TI  - A new species of bunchgrass lizard (Squamata: Phrynosomatidae) from the southern
      sky islands of the Sierra Madre Occidental, Mexico.
AB  - A new species of bunchgrass lizard in the Sceloporus scalaris group is described
      from the southern portion of the Sierra Madre Occidental in Mexico. The new
      species, Sceloporus aurantius sp. nov., was previously confused with S. brownorum
      but differs from this and all but one species within the S. scalaris group by a
      lack of blue belly patches in males. It shares with S. chaneyi an absence of blue
      belly patches, but differs from this species in size, number of dorsal scales,
      number of scales around midbody, and presence of an un-patterned morph. The new
      species further differs from S. chaneyi, and all other species in the S. scalaris
      species group, by unique phylogenetic position revealed through species
      delimitation based on multi-locus nuclear DNA. Principal component analyses of 24
      traditional morphological characters used to describe previous S. scalaris group
      taxa indicate that these characters may be of limited use to delineate species in
      this species group. However, male lateral and ventral coloration may still be an
      important character for diagnosing species. 

PMID- 24869878
TI  - Description of three new species of Ooencyrtus (Hymenoptera: Encyrtidae) from
      China.
AB  - Hymenoptera parasitoids of Megaloptera, particularly the family Corydalidae, are
      rarely found. Ooencyrtus Ashmead is a genus that attacks eggs of many orders of
      Insecta, including Megaloptera. Here, three species, O. longicauda sp. n., O.
      noyesi sp. n. and O. protohermeasis sp. n. are described. Two of them, O.
      longicauda and O. protohermesis were reared from eggs of corydalids (Megaloptera:
      Corydalidae). The three new species and O. yoshidai Noyes & Hirose are included
      in the newly established protohermesis species-group of Ooencyrtus because of
      shared similar morphological characters and what is apparently a shared host
      family (unknown for O. noyesi). 

PMID- 24869879
TI  - A new species of Ituglanis from the Rio Xingu Basin, Brazil, and the evolution of
      pelvic fin loss in trichomycterid catfishes (Teleostei: Siluriformes:
      Trichomycteridae).
AB  - A new species of the trichomycterid catfish genus Ituglanis is described from the
      Rio Curua, Rio Xingu basin, Rio Amazonas drainage, Brazil. Ituglanis apteryx, new
      species, is promptly distinguished from congeners, except some specimens of I.
      parahybae (Eigenmann), by the absence of pelvic fins, girdle, and muscles. The
      new species differs from I. parahybae in the pattern of the cephalic
      laterosensory system; the absence of a posterior cranial fontanel; the presence
      of an epural; and the number of branchiostegal rays, ribs, and vertebrae.
      Ituglanis apteryx is one among the several trichomycterids lacking pelvic fins.
      Analysis reveals that pelvic fin loss independently evolved several times during
      the trichomycterid radiation. 

PMID- 24869880
TI  - Description of Chlorogomphus auripennis spec. nov. from Guangdong Province, with
      new records of Chlorogomphidae from Yunnan Province, China (Odonata:
      Chlorogomphidae).
AB  - A new chlorogomphid, Chlorogomphus (Orogomphus) auripennis spec. nov. (holotype
      male; Mt Nankunshan, Longmen County, Guangdong Province, China, 20. V. 2008) is
      described and illustrated. It is the first species belonging to the subgenus
      Orogomphus recorded from mainland China. The holotype will be deposited in the
      Collection of Aquatic Animals, Institute of Hydrobiology, Chinese Academy of
      Sciences, Wuhan City, Hubei Province, China. Chlorogomphus auratus Martin, 1910
      and Chloropetalia selysi (Fraser, 1929) are recoded from Chinese territory for
      the first time. The total number of Chlorogomphidae in China reaches 20.
      Description of the hitherto unknown female of Chlorogomphus yokoii Karube, 1995
      is provided. 

PMID- 24869881
TI  - Description of the larva and biological notes on Vermiophis taihangensis Yang &
      Chen, 1993 (Diptera: Vermileonidae) from China.
AB  - Unmixed colonies of larval antlions and wormlions in similar pits were found in
      the Xiaolongmen National Forest Park in the Taihang Shan, China. A male of
      Vermiophis taihangensis Yang & Chen, 1993 was reared from a larva and a
      morphological description of the third instar larval wormlion is presented. The
      larva of Vermiophis taihangensis differs from the related species V. ganquanensis
      Yang, 1979 in the well developed sclerotized stigmata on abdominal segment 4, but
      is similar in the structure of the lateral row of setae and the same number of
      spines (6) on the pseudopod on the abdominal segment 1.  

PMID- 24869884
TI  - The genus Exogone (Polychaeta: Syllidae) from the Brazilian coast, with the
      description of a new species.
AB  - A new species of Exogone, E. gigas sp. n., is described herein, together with E.
      africana, E. arenosa, E. dispar, E. naidinoides, E. rolani, and E. simplex,
      collected along the Brazilian coast, including new morphological details. The
      distribution of E. breviantennata is expanded to include the states of Espirito
      Santo, Paraiba and Pernambuco. Exogone gigas sp. n. is characterized by having a
      large median antenna, the absence of dorsal cirri on chaetiger 2, and having a
      triangular process and minute spines on the shaft of the spiniger-like chaetae on
      chaetiger 2. The Brazilian specimens are compared to the morphologically most
      similar congeners. A key for the species described in this paper is provided. 

PMID- 24869882
TI  - Publication and dating of Parts IV-VII of Brauer & Bergenstamm's Die Zweiflugler
      des Kaiserlichen Museums zu Wien (1889-1894).
AB  - Based on new evidence, the dates of publication of the journal and separate
      versions of parts IV-VII of Brauer & Bergenstamm's Die Zweiflugler des
      Kaiserlichen Museums zu Wien are given, correcting those dates previously
      published. 

PMID- 24869885
TI  - Two new species of Selitrichodes (Hymenoptera: Eulophidae: Tetrastichinae)
      inducing galls on Casuarina (Casuarinaceae).
AB  - Two new species of gall-inducing wasps, Selitrichodes casuarinae Fisher & La
      Salle sp. n. and Selitrichodes utilis Fisher & La Salle sp. n., are described
      from Micronesia (Guam, Rota and Palau Islands) and Australia respectively. These
      species induce galls on Casuarina and can cause extensive damage to the trees.
      Their status as pest or beneficial species is discussed. 

PMID- 24869887
TI  - Revision of Lepidonopsis humilis (Augener, 1922) and description of L. barnichae
      sp. nov. (Annelida: Polychaeta: Polynoidae) based upon morphological and
      molecular characters.
AB  - Lepidonopsis humilis (Augener, 1922) has been considered as an amphiamerican
      species, widely recorded in both the Grand Caribbean region and the Tropical
      Eastern Pacific. Based on type material and additional materials, L. humilis is
      redescribed herein and its distribution clarified and restricted. Furthermore,
      the identity of specimens from the Mexican Pacific is clarified and a new species
      L. barnichae sp. nov. is described. This species is characterized by conical
      macrotubercles with slightly curved tips; all elytra with a tuft of papillae on
      the surface, isolated from the marginal papillae; and the second segment dorsally
      projecting over the prostomium as a small lobe. Additionally, there is a 17.6%
      genetic divergence in the nucleotide sequence variation of COI between L. humilis
      and L. barnichae sp. nov., which supports the morphological differences observed.
      Thus, L. humilis does not have an amphiamerican distribution but is restricted to
      the Gran Caribbean region; whereas the specimens from the Tropical Eastern
      Pacific belong to the newly described species L. barnichae sp. nov. A key to the
      three known species of Lepidonopsis is included. 

PMID- 24869886
TI  - Garra waensis, a new cyprinid fish (Actinopterygii: Cypriniformes) from the Nan
      River Basin of the Chao Phraya River system, northern Thailand.
AB  - A new cyprinid fish, Garra waensis, is described from the Wa River, a tributary
      of the Nan River of the Chao Phraya River system in northern Thailand. The
      species is distinguishable from its congeners by the combination of the following
      characters: the absence of barbels; 7 branched dorsal fin rays; 31-37 lateral
      line scales; 10-12 circumpeduncular scales; a small and broad head (head length
      [HL] 22.7-26.1% in standard length, head depth 56.1-64.9% HL, head width 74.0
      85.0 % HL); a weakly developed proboscis in front of nostrils; the presence of
      reddish-orange spots (white or dull yellowish white in preserved specimens) on
      the side of the body; and a dark mid-lateral stripe running from the upper edge
      of the gill opening to the caudal peduncle and expanding into a large anteriorly
      pointed triangular blotch at the end of the body (in preserved condition). A
      vomero-palatine organ of the species is also described in detail for the first
      time for Asian species of Garra. The genus Placocheilus is treated as a junior
      synonym of Garra.  

PMID- 24869888
TI  - Chewing lice (Phthiraptera: Amblycera, Ischnocera) from Red Sea gulls with new
      host-parasite records.
AB  - Knowledge about chewing lice from marine birds of the Red Sea is minimal. Five
      species of gulls were examined for chewing lice in three different localities of
      the Saudi Arabian Red Sea coast. Two gull species were examined for lice for the
      first time (Larus armenicus Buturlin, 1934 and Larus michahellis Naumann, 1840)
      and their lice represent new host-louse associations. Four species and two
      subspecies of lice were identified from 159 specimens collected. Actornithophilus
      piceus lari (Packard, 1870) and Austromenopon transversum (Denny, 1842)
      (suborder: Amblycera), and Quadraceps punctatus (Burmeister, 1838) and
      Saemundssonia lari (O. Fabricius, 1780) (suborder: Ischnocera) were recorded for
      the first time from Saudi Arabia and Red Sea birds. Taxonomic and ecological
      notes, type hosts, data on specimens examined, collecting localities, an
      identification key, and photographs of each species and subspecies are given.  

PMID- 24869889
TI  - Ultrastructure of antennal sensilla in Hydrotaea armipes (Fallen) (Diptera:
      Muscidae): new evidence for taxonomy of the genus Hydrotaea.
AB  - The morphology and ultrastructure of the antennal sensilla of male Hydrotaea
      (Hydrotaea) armipes (Fallen) are examined via scanning electron microscopy in
      order to highlight the importance of antennal sensilla as a source of
      morphological characters for taxonomy and phylogeny of Hydrotaea. Antennal scape
      and pedicel have only one type of sensilla, the sharp-tipped chaetic sensilla,
      whereas antennal funiculus possesses several types of sensilla, including
      trichoid sensilla, two subtypes of basiconic sensilla, coeloconic sensilla and
      clavate sensilla. These results are compared with previously published studies on
      other fly species, especially on H. (H.) irritans (Fallen) and H. (Ophyra)
      chalcogaster (Wiedemann), and there are possible uniquely derived characters or
      diagnostic characters examined on antennal pedicel and antennal funiculus, which
      suggests either affinities and divergence between species at subgenus level.
      Thus, new morphological evidence is provided, which might help to develop the
      much disputed taxonomy of genus Hydrotaea Robineau-Desvoidy in future. 

PMID- 24869890
TI  - Redescription of 'Polyzonium' malagassum, a new synonym of Rhinotus purpureus
      (Pocock, 1894), with notes about the occurrence of the order Polyzoniida on
      Madagascar (Diplopoda).
AB  - Polyzonium malagassum de Saussure & Zehntner, 1902, the only indigenous record of
      the order Polyzoniida from Madagascar, is redescribed after a study of the type
      specimens. The only male specimen is selected as the lectotype and illustrated.
      P. malagassum is discovered to be a synonym of the widespread tropical tramp
      species Rhinotus purpureus (Pocock, 1894). A mapping of additional locality data
      of R. pupureus shows that the species is widespread in Malagasy rainforests and
      montane rainforests, and occurs locally in high densities. Seven potentially
      indigenous Polyzoniida morphospecies also occur on Madagascar, but these
      undescribed species are more localized and show a lower abundance than R.
      purpureus. Brief notes, locality data, and Museum acronyms are given for the
      undescribed Polyzoniida species, which will hopefully assist future studies on
      Malagasy representatives of this little-known but biogeographically interesting
      order. With the discovery of the ubiquitous presence of R. purpureus on
      Madagascar, the similarity of the defense secretions of South American and of
      endemic Malagasy poison dart frogs (family Mantellidae) might derive from the
      fact that both groups prey on and sequester alkaloids from the same species of
      millipede.  

PMID- 24869891
TI  - A new Rhagovelia (Hemiptera: Heteroptera: Veliidae) from the Brazilian Amazon,
      with a key to species of the robusta group known from the country.
AB  - Rhagovelia zecai sp. nov., from the Brazilian Amazon, is described, illustrated,
      compared with similar species, and included in a key to species of the robusta
      group recorded from the country. 

PMID- 24869892
TI  - Nomenclatural notes on the Eurytomids (Chalcidoidea: Eurytomidae) described by
      Jean Brethes housed in Museo Argentino de Ciencias Naturales "Bernardino
      Rivadavia".
AB  - Ten Eurytomidae (Hymenoptera) parasitic wasp species described by Jean Brethes
      and deposited in the Museo Argentino de Ciencias Naturales in Buenos Aires are
      treated and their nomenclature stabilized. The condition of the type material is
      described. Lectotypes are designated for Decatoma cecidosiphaga Brethes,
      Prodecatoma parodii Brethes, Eudecatoma opposita Brethes, and Eurytoma caridei
      Brethes. One new generic synonymy, Xanthosomodes Brethes with Tetramesa Walker,
      n. syn., and five new combinations are proposed: Tetramesa albiangulata
      (Brethes), n. comb.; Phylloxeroxenus caridei (Brethes), n. comb.; Aximopsis
      vulgata (Brethes), n. comb.; Proseurytoma parodii (Brethes), n. comb.; and
      Bruchophagus opposita (Brethes), n. comb. Sycophila paranensis Brethes is
      declared incertae sedis. 

PMID- 24869894
TI  - Accidents at work and costs analysis: a field study in a large Italian company.
AB  - Accidents at work are still a heavy burden in social and economic terms, and
      action to improve health and safety standards at work offers great potential
      gains not only to employers, but also to individuals and society as a whole.
      However, companies often are not interested to measure the costs of accidents
      even if cost information may facilitate preventive occupational health and safety
      management initiatives. The field study, carried out in a large Italian company,
      illustrates technical and organisational aspects associated with the
      implementation of an accident costs analysis tool. The results indicate that the
      implementation (and the use) of the tool requires a considerable commitment by
      the company, that accident costs analysis should serve to reinforce the
      importance of health and safety prevention and that the economic dimension of
      accidents is substantial. The study also suggests practical ways to facilitate
      the implementation and the moral acceptance of the accounting technology. 

PMID- 24869895
TI  - Electrochemical quartz crystal microbalance (EQCM) study of ion dynamics in
      nanoporous carbons.
AB  - Electrochemical quartz crystal microbalance (EQCM) and cyclic voltammetry (CV)
      measurements were used to characterize ion adsorption in carbide-derived carbon
      (CDC) with two different average pore sizes (1 and 0.65 nm), from neat and
      solvated 1-Ethyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide (EMI
      TFSI) electrolytes. From the electrode mass change in neat EMI-TFSI, it was shown
      that one net charge stored corresponds almost to one single ion at high
      polarization; in that case, no ion-pairing or charge screening by co-ions were
      observed. In 2 M EMI-TFSI in acetonitrile electrolyte, experimental solvation
      numbers were estimated for EMI(+) cation, showing a partial desolvation when
      cations were adsorbed in confined carbon pores. The extent of desolvation
      increased when decreasing the carbon pore size (from 1 down to 0.65 nm). The
      results also suggest that EMI(+) cation owns higher mobility than TFSI(-) anion
      in these electrolytes. 

PMID- 24869893
TI  - Psychosocial work factors, blood pressure and psychological strain in male bus
      operators.
AB  - The research aim was to predict the bus operators' blood pressure (BP) and
      psychological strain using a combination of the Job-Demand Control (JDC) and
      Effort-Reward Imbalance (ERI) models. The study was conducted with a sample of
      139 bus operators in the city of Bogota (Colombia), who answered a questionnaire
      that included the Job Content Questionnaire (JCQ), the ERI Questionnaire, and the
      General Health Questionnaire (GHQ). Four consecutive BP readings taken in the
      workplace were averaged to calculate an estimation of the bus operators' BP. By
      conducting multiple linear regressions it was found that, taken together, JDC and
      ERI models explain 10% (F(11,139)=2,502; p=0.00) of systolic BP variance, and 34%
      (F(6,139)=8,638; p=0.00) of psychological strain variance. These results suggest
      that the JDC and ERI predictors provide complementary information which increases
      the probability of accurately model the bus operators' health. 

PMID- 24869896
TI  - Postoperative apnea and hypercapnia due to intentional breath holding in a
      freediver.

PMID- 24869897
TI  - Can we keep our mothers happy and our babies safe?

PMID- 24869898
TI  - Photothermal laser microsintering of nanoporous gold.
AB  - Photothermal processing of nanoporous gold using a microfocused continuous-wave
      laser at a wavelength of 532 nm and a 1/e(2) spot diameter of 2.9 MUm has been
      studied. In addition, complementary experiments have been carried out via
      conventional annealing. Scanning electron microscopy has been used for
      characterization. Local laser irradiation at distinct laser powers and pulse
      lengths results in coarsening of the porous gold structures. During laser
      processing the pore size of the native nanoporous gold increases to maximum
      values in the range of 0.25-3 MUm. The affected areas exhibit lateral dimensions
      in the range of 2-10 MUm. Overall two regions are distinguished. An inner region,
      where large pores and ligaments are formed and an outer region, where the pore
      size and ligament size gradually change and approach the feature sizes of the
      native material. A qualitative thermokinetic model allows one to reproduce the
      experimentally observed dependence of the laser-induced morphologies on the laser
      parameters. On the basis of this model the underlying processes are attributed to
      sintering and melting of the gold structures. The presented results demonstrate
      the prospects of photothermal laser processing in engineering porous gold with
      spatially varying porosities on micrometer to nanometer length scales. 

PMID- 24869899
TI  - A survey of public attitudes towards barking dogs in New Zealand.
AB  - AIMS: To investigate public attitudes towards barking dogs in New Zealand in
      order to quantify the extent to which people perceive barking dogs to be a
      problem, to compare tolerance of barking with that of other common suburban
      noises, to assess the level of public understanding about the function of
      barking, to determine risk factors for intolerance of barking and to assess
      knowledge of possible strategies for the investigation and management of problem
      barking. METHODS: A 12-page questionnaire was sent to 2,000 people throughout New
      Zealand randomly selected from the electoral roll. Risk factors for being
      bothered by barking were examined using logistic regression analysis. RESULTS: A
      total of 1,750 questionnaires were successfully delivered; of these, 727 (42%)
      were returned. Among respondents, 356/727 (49.0%) indicated that frequent barking
      during the day would bother them while 545/727 (75.0%) would be bothered by
      barking at night. Barking and howling were ranked above other suburban noises as
      a cause of annoyance. Risk factors for being bothered by daytime barking were not
      being home during the day, not owning a dog, and considering a dog bite to be a
      serious health risk. Risk factors for being bothered by night-time barking were
      not being home during the day, marital status, considering dog bites to pose a
      serious health risk, and having been frightened by a dog. Overall, 510/699 (73%)
      respondents understood that barking was a form of communication. Action likely to
      be taken by 666 respondents hearing frequent barking included notifying and
      offering to help the owner (119; 17.8%), complaining to the owner (127; 19.1%) or
      the authorities (121; 18.2%), or doing nothing (299; 48%). Possible responses by
      211 dog owners if they had a barking dog included seeking help from dog trainers
      (59; 28%) or behaviourists (54; 26%), buying an anti-barking device (33; 15%) or
      getting rid of the dog (20; 10%). CONCLUSIONS: Barking was considered to be
      potentially disturbing by respondents to this survey. Attitudes towards barking
      were most influenced by age, dog ownership, past experience with dogs and
      attitude towards dog bites. Public understanding of the possible reasons for
      barking and appropriate methods of managing the behaviour when it becomes a
      problem could be improved by better education and the provision of information
      through veterinary clinics and social media.

PMID- 24869900
TI  - Fracture resistance of commonly used self-drilling orthodontic mini-implants.
AB  - OBJECTIVE: To investigate the fracture resistance of six commonly used self
      drilling orthodontic mini-implants by comparing their respective fracture torques
      during insertion. MATERIALS AND METHODS: Ninety self-drilling mini-implants from
      six manufacturers (Aarhus, Dual-Top, OrthoEasy, Tomas-pin, Unitek, and
      VectorTAS), with diameters ranging from 1.4 to 1.8 mm, were inserted into acrylic
      blocks using a custom-made insertion device. Insertion torques were measured
      using a 6-degree-of-freedom load cell fixed to the base of the acrylic blocks,
      and peak torques experienced at the time of fracture for each of the mini
      implants were recorded. One-way analysis of variance (alpha  =  .05) was used to
      compare the fracture torques among the six different groups. RESULTS: Statistical
      analysis revealed significant differences (P < .05) in the peak fracture torques
      among mini-implant groups. Mean fracture torques ranked as follows: Unitek (72
      Ncm) > Tomas-pin (36 Ncm) > Dual-Top (32 Ncm) ~ VectorTAS (31 Ncm) > OrthoEasy
      (28 Ncm) > Aarhus (25 Ncm), with significant differences found between all
      manufacturers, except for Dual-Top and VectorTAS. CONCLUSIONS: Mini-implants
      tested showed a wide range of torque at fracture depending on the manufacturer,
      with only a weak correlation between mini-implant diameter and fracture
      resistance. This torque should be considered at the time of mini-implant
      insertion to minimize the risk of implant fracture, especially in areas of high
      density bone without predrilling.

PMID- 24869901
TI  - Patient compliance with Hawley retainers fitted with the SMART((r)) sensor: a
      prospective clinical pilot study.
AB  - OBJECTIVE: To evaluate the compliance of patients while wearing maxillary Hawley
      retainers embedded with SMART microsensors. METHODS: The sample population
      consisted of 22 patients who were divided into an experimental (group A) and a
      control group (group B). Group A was informed that they would be monitored
      through the use of SMART microsensors, while group B was not informed that they
      would be monitored. After the delivery of the retainers (T0), the patients were
      evaluated at T1 and T2, represented by 6- and 12-week follow-up visits,
      respectively. At T1, group B was informed of our ability to monitor their
      compliance. Both groups continued wearing their retainers during T1 to T2.
      RESULTS: During T0-T1, Group A wore their retainers for an average of 16.3 hours
      (SD 4.39), while group B wore their appliances for an average of 10.6 hours (SD
      5.36, t  =  2.426, P  =  .027). Although group B increased their retainer wear by
      0.5 hours/day from T1 to T2, this increase was not statistically significant.
      CONCLUSIONS: Despite significant differences being noted between the two groups
      at T1, group B did not show significant mean changes in their wear time before
      and after becoming aware of the use of the SMART microsensor.

PMID- 24869904
TI  - Treatment of late-presenting Monteggia variant with an isolated, simple flexion
      ulnar osteotomy.
AB  - Radial head dislocation in children is usually associated with complete elbow
      dislocation or occurs as a part of a Monteggia injury. In patients without an
      obvious fracture of the ulna, recognizing that plastic deformation of the ulna
      leads to pathological bowing is a key concept in the management of this injury.
      Although good results have been published using osteotomy of the ulna to maintain
      stability after open reduction, we hypothesize that ulnar osteotomy alone may be
      enough to enable stable enlocation of an irreducible radial head in patients who
      are identified early. We present two cases of irreducible radial head
      dislocation, treated with ulnar osteotomy and closed radial head reduction. Both
      osteotomies united and both patients had an excellent functional outcome with the
      absence of pain or deformity and early return to function. We explain the
      surgical technique and compare the outcomes with alternative surgical treatments.

PMID- 24869902
TI  - Carbon nanotube electron field emitters for x-ray imaging of human breast cancer.
AB  - For imaging human breast cancer, digital breast tomosynthesis (DBT) has been
      shown to improve image quality and breast cancer detection in comparison to two
      dimensional (2D) mammography. Current DBT systems have limited spatial resolution
      and lengthy scan times. Stationary DBT (s-DBT), utilizing an array of carbon
      nanotube (CNT) field emission x-ray sources, provides increased spatial
      resolution and potentially faster imaging than current DBT systems. This study
      presents the results of detailed evaluations of CNT cathodes for x-ray breast
      imaging tasks. The following were investigated: high current, long-term stability
      of CNT cathodes for DBT; feasibility of using CNT cathodes to perform a 2D
      radiograph function; and cathode performance through several years of imaging.
      Results show that a breast tomosynthesis system using CNT cathodes could run far
      beyond the experimentally tested lifetime of one to two years. CNT cathodes were
      found capable of producing higher currents than typical DBT would require,
      indicating that the s-DBT imaging time can be further reduced. The feasibility of
      using a single cathode of the s-DBT tube to perform 2D mammography in 4 s was
      demonstrated. Over the lifetime of the prototype s-DBT system, it was found that
      both cathode performance and transmission rate were stable and consistent.

PMID- 24869905
TI  - Unilateral versus bilateral clubfoot: an analysis of severity and correlation.
AB  - This study compares the severity of unilateral and bilateral clubfoot, and the
      correlation between right and left feet of bilateral cases. Sixty-six unilateral
      and 75 bilateral clubfoot patients were assessed for severity using the Pirani
      score at an average age of 12.9 days (SD 9 days). In bilateral cases, the
      severity of right and left feet was highly correlated (r=0.68). The odds of being
      very severe were 2.6 (95% confidence interval 1.3-5.1) times higher in bilateral
      cases (P=0.007). Bilateral and unilateral clubfeet present with differing
      severity. Right and left feet from bilateral cases are highly correlated.
      Researchers need to address these issues during study design and analysis. 

PMID- 24869906
TI  - Influence of exposure factors on the variability of CBCT voxel values: a phantom
      study.
AB  - OBJECTIVES: To assess the influence of milliamperage and kilovolt peak (kVp) on
      the variability of cone beam CT (CBCT) voxel values. METHODS: CBCT scans were
      obtained from radiographic phantoms in varying concentrations of dipotassium
      hydrogen phosphate solutions (200-1200 mg ml(-1)) under different protocols of
      milliamperage and kVp. In addition, scans were performed with and without a
      dental implant and exo-mass. The variability of CBCT voxel values was measured on
      each scan, and factorial analysis of variance and the post hoc Tukey test were
      performed (alpha = 0.05). Linear regression was performed to assess the
      relationship between voxel value variability and dipotassium hydrogen phosphate
      concentration. RESULTS: milliamperage and the presence of a dental implant did
      not produce significant interference (p = 0.28 and 0.87, respectively) in voxel
      value variability. Scans at the highest kVp value presented a significant
      reduction (p <= 0.0001) in voxel value variability when only exo-mass was not
      present. Voxel value variability was not influenced by exo-mass in scans at the
      highest levels of milliamperage and kVp. The presence of exo-mass produced a
      significant reduction (p <= 0.0001) in voxel value variability in most of the
      scans. Higher concentrations yielded greater variations in voxel values in all
      scans, except for those operating at the highest levels of mAs and kVp.
      CONCLUSIONS: mAs did not influence the variability of CBCT voxel values; higher
      kVp reduced such variability when only the object was smaller than the field of
      view.

PMID- 24869907
TI  - Low-dose 5-aza-2'-deoxycytidine pretreatment inhibits experimental autoimmune
      encephalomyelitis by induction of regulatory T cells.
AB  - Forkhead box P3 (Foxp3) is the major transcription factor controlling the
      development and function of regulatory T (Treg) cells. Previous studies have
      indicated epigenetic regulation of Foxp3 expression. Here, we investigated
      whether the deoxyribonucleic acid (DNA) methyltransferase inhibitor 5-aza-2'
      deoxycytidine (5-Aza) applied peripherally could modulate central nervous system
      (CNS) inflammation, by using a mouse experimental autoimmune encephalomyelitis
      (EAE) model. We found that disease activity was inhibited in a myelin
      oligodendrocyte glycoprotein (MOG) peptide-induced EAE mouse briefly pretreated
      with low-dose (0.15 mg/kg) 5-Aza, ameliorating significant CNS inflammatory
      responses, as indicated by greatly decreased proinflammatory cytokines. On the
      contrary, control EAE mice expressed high levels of IFN-gamma and interleukin
      (IL)-17. In addition, 5-Aza treatment in vitro increased GFP expression in
      CD4(+)GFP(-) T cells isolated from GFP knock-in Foxp3 transgenic mice.
      Importantly, 5-Aza treatment increased Treg cell numbers, in EAE mice, at both
      disease onset and peak. However, Treg inhibition assays showed 5-Aza treatment
      did not enhance per-cell Treg inhibitory function, but did maintain a lower
      activation threshold for effector cells in EAE mice. In conclusion, 5-Aza
      treatment prevented EAE development and suppressed CNS inflammation, by
      increasing the number of Treg cells and inhibiting effector cells in the
      periphery. 

PMID- 24869909
TI  - Intravascular device use, management, documentation and complications: a point
      prevalence survey.
AB  - OBJECTIVE: To examine the use, management, documentation and complications for
      intravascular devices in cardiac, medical and surgical inpatients. METHODS: A
      point prevalence survey was undertaken in a large tertiary hospital in
      Queensland. Descriptive statistics were used to analyse data. RESULTS: Of the 327
      patients assessed, 192 (58.7%) had one or more devices in situ. Of the 220
      devices, 190 (86.4%) were peripheral venous catheters, 25 (11.4%) were
      peripherally inserted central catheters and five (2.3%) were central venous
      catheters. Sixty-two of 220 devices (28.2%) were in situ without a clear purpose,
      whereas 54 (24.7%) had one or more complications, such as redness, pain,
      tracking, oedema or oozing. There was no documentation on the daily patient care
      record to indicate that a site assessment had occurred within the past 8h for 25%
      of the devices in situ. CONCLUSIONS: The present study identified several
      problems and highlighted areas for improvement in the management and
      documentation for intravascular devices. Ongoing education, promoting good
      clinical practice and reauditing, can be applied to improve the management of
      devices.

PMID- 24869908
TI  - Correlation between PDZK1, Cdc37, Akt and breast cancer malignancy: the role of
      PDZK1 in cell growth through Akt stabilization by increasing and interacting with
      Cdc37.
AB  - PDZ domain containing 1 (PDZK1) is a scaffold protein that plays a role in the
      fate of several proteins. Estrogen can induce PDZK1 gene expression; however, our
      recent report showed that PDZK1 expression in the breast cancer cell line MCF-7
      is indirect and involves insulin-like growth factor (IGF)-1 receptor function.
      Such a relationship was established in cell culture systems and human breast
      cancer tissues. Here we show that overexpression of PDZK1 promoted an increase in
      cyclin D1 and enhanced anchorage-independent growth of MCF-7 cells in the absence
      of 17beta-estradiol, suggesting that PDZK1 harbors oncogenic activity. Indeed,
      PDKZ1 overexpression enhanced epidermal growth factor receptor (EGFR)-stimulated
      MEK/ERK1/2 signaling and IGF-induced Akt phosphorylation. PDZK1 appeared to play
      this role, in part, by stabilizing the integrity of the growth promoting factors
      Akt, human epidermal growth factor receptor 2 (Her2/Neu) and EGFR. Increased Akt
      levels occurred via a decrease in the ubiquitination of the kinase. PDZK1
      overexpression was associated with resistance to paclitaxel/5
      fluorouracil/etoposide only at low concentrations. Although the increased
      stability of Akt was sensitive to heat shock protein 90 (HSP90) inhibition,
      increased levels of the cochaperone cell division cycle 37 (Cdc37), as well as
      its ability to bind PDZK1, appear to play a larger role in kinase stability.
      Using human tissue microarrays, we show strong positive correlation between
      PDZK1, Akt and Cdc37 protein levels, and all correlated with human breast
      malignancy. There were no positive correlations between PDZK1 and Cdc37 at the
      mRNA levels, confirming our in vitro studies. These results demonstrate a
      relationship between PDZK1, Akt and Cdc37, and potentially Her2/Neu and EGFR, in
      breast cancer, representing a new axis that can be targeted therapeutically to
      reduce the burden of human breast cancer. 

PMID- 24869910
TI  - A case of unprovoked venous thromboembolism in a marathon athlete presenting
      atypical sequelae: What are the chances?
AB  - Marathon runners are exposed to multiple thrombogenic risk factors including
      dehydration and hemoconcentration, injury and inflammation, long-distance travel
      between events, and contraceptive usage. However, despite awareness about
      thromboembolism and several case reports detailing life-threatening
      hypercoagulopathies in athletes, the prevalence of venous thromboembolism in
      marathon runners remains uncharted. There is a lack of data and evidence-based
      guidelines for these athletes and for healthcare providers, including general
      medical practitioners and sports physicians. We present an episode of unprovoked
      deep vein thrombosis (DVT) and pulmonary embolism (PE) in a female marathon
      athlete who presented with atypical sequelae over the course of 8 months, and
      identify some "easy-to-miss" warning signs and symptoms. Through dialogue with
      the patient regarding their personal questions and anxieties surrounding
      idiopathic DVT-PE, we identify a clear need for more accessible information and
      comprehensive research concerning the detection, prevalence, and long-term
      management of venous thromboembolism in athletes. We discuss the possibility that
      being an athlete might constitute a more significant risk factor for venous
      thromboembolism than is currently estimated by commonly used diagnostic protocols
      and conclude that there is quite possibly a need for more specific clinical
      guidelines for athletes in this area. 

PMID- 24869914
TI  - Magnetic anisotropy in a spin 1/2 quasi-one-dimensional antiferromagnetic
      copper(II) complex CuCl2(pdz) with a staggered g-tensor.
AB  - We report an unusual magnetic anisotropy in a S = 1/2 1D antiferromagnetic (AF)
      compound CuCl2(pdz) (pdz = pyridazine). The magnetic susceptibility for H//a* and
      H//c showed characteristic behavior in the S = 1/2 1D Heisenberg AF system,
      whereas that for H//b exhibited a 1/T contribution. The origin of such an
      anomalous anisotropy in the magnetic susceptibility is explained by the staggered
      g-tensor of this compound. 

PMID- 24869912
TI  - Nano-petri-dish array assisted glancing angle sputtering for Ag-NP assembled bi
      nanoring arrays as effective SERS substrates.
AB  - Nano-petri-dish array assisted glancing angle Ag-sputtering was reported to
      synthesize Ag-nanoparticle (Ag-NP) assembled bi-nanoring arrays as surface
      enhanced Raman scattering (SERS) substrates. By manipulating the sputtering-Ag
      duration, the gaps between the Ag-NPs in the bi-nanorings are tunable to acquire
      optimal electromagnetic field enhancement, and the ordered bi-nanoring arrays
      ensure excellent reproducibility for Raman measurement. Such as-fabricated Ag-NPs
      assembled nanoring arrays exhibit excellent SERS performance, not only 1 * 10(
      12) M rhodamine 6G has been identified, but also polychlorinated biphenyls with a
      low concentration down to 1 * 10(-9) M has been recognized, showing great
      potential in the detection of trace organic pollutants in the environment. 

PMID- 24869911
TI  - Comparison of echocardiographic and pressure-volume loop indices of systolic
      function in patients with single ventricle physiology: a preliminary report.
AB  - BACKGROUND: Differences in ventricular geometry and physiology of patients with
      single ventricle anatomy complicate the application of traditional, noninvasive
      measurements of systolic function. We compared noninvasive measures of
      ventricular systolic function in single ventricle patients with invasive measures
      to evaluate their validity in this population. METHODS: A secondary analysis of
      patients with single ventricle physiology enrolled in the multi-institutional
      research project, "multi-scale modeling of single ventricle hearts," was
      performed. Pressure-volume loops (PVLs) were recorded using microconductance
      catheters. Transthoracic echocardiogram and cardiac magnetic resonance imaging
      were performed on the same day. PVL indices of systolic function including end
      systolic elastance (Ees), maximal rate of pressure increase (dP/dTmax), and
      stroke work indexed to end-diastolic volume (SW/EDV) were compared with
      noninvasive measures, including echocardiographic myocardial performance index
      (MPI), rate of pressure rise (AV valve dP/dT), isovolumic acceleration,
      longitudinal shortening fraction (longSF), and fractional area change (FAC).
      RESULTS: Fifteen patients had PVLs available for analysis. Eleven had a dominant
      right ventricle, three were status poststage 1 repair, five had superior
      cavopulmonary anastomosis, and seven had a total cavopulmonary anastomosis. FAC
      correlated with Ees (r = 0.69, P < .01), SW/EDV (r = 0.64, P = .01), and dP/dTmax
      (r = 0.59, P = .03). LongSF correlated with dP/dTmax (r = 0.61, P = .02) MPI, AV
      valve dP/dT, and isovolumic acceleration did not correlate with pressure-volume
      loop indices of systolic function. CONCLUSIONS: Obtaining PVLs via
      microconductance catheters can reliably be performed in the single ventricle
      population and serve as a method to validate echocardiographic indices in this
      high-risk population. Of the echocardiographic variables, FAC showed the best
      correlation with PVL indices. Future studies controlling for stage of palliation
      should be performed to further validate echocardiographic measures of systolic
      function in this patient population.

PMID- 24869915
TI  - A comparison of the medium-term impact and recovery of the Pakistan floods and
      the Haiti earthquake: objective and subjective measures.
AB  - INTRODUCTION: The 2010 Haiti earthquake and Pakistan floods were similar in their
      massive human impact. Although the specific events were very different, the
      humanitarian response to disasters is supposed to achieve the same ends. This
      paper contrasts the disaster effects and aims to contrast the medium-term
      response. METHODS: In January 2011, similarly structured population-based surveys
      were carried out in the most affected areas using stratified cluster designs
      (80*20 in Pakistan and 60*20 in Haiti) with probability proportional to size
      sampling. RESULTS: Displacement persisted in Haiti and Pakistan at 53% and 39% of
      households, respectively. In Pakistan, 95% of households reported damage to their
      homes and loss of income or livelihoods, and in Haiti, the rates were 93% and
      85%, respectively. Frequency of displacement, and income or livelihood loss, were
      significantly higher in Pakistan, whereas disaster-related deaths or injuries
      were significantly more prevalent in Haiti. CONCLUSION: Given the rise in
      disaster frequency and costs, and the volatility of humanitarian funding streams
      as a result of the recent global financial crisis, it is increasingly important
      to measure the impact of humanitarian response against the goal of a return to
      normalcy.

PMID- 24869916
TI  - Modeling the effect of phase II conjugations on topoisomerase I poisoning: pilot
      study with luteolin and quercetin.
AB  - Topoisomerases are targeted by several drugs in cancer chemotherapy acting as key
      enzymes in cell viability. Some flavonoids and their glycosides may exert health
      protective effects through the poisoning of topoisomerases. However, previous
      studies did not consider the substantial modifications taking place after
      ingestion neglecting that only metabolites can interact with the internal
      compartments of the human body. Since the high number of possible metabolites
      hinders their systematic analysis, an in silico approach can be a valuable tool
      to prioritize compounds by identifying candidates for further characterization.
      Specifically focusing on luteolin and quercetin, among the most ubiquitous
      flavonoids in the human diet, this work reports a computational procedure to
      model the effect of hepatic phase II conjugative metabolism on poisoning of human
      Topoisomerase I. As a general effect, glucuronidation and sulphation might
      enhance and quench poisoning activity, respectively. Among all, quercetin-3-O
      glucuronide represents a promising candidate to be analyzed more thoroughly. 

PMID- 24869917
TI  - Hydrogen atom transfer from 1,n-alkanediamines to the cumyloxyl radical.
      Modulating C-H deactivation through acid-base interactions and solvent effects.
AB  - A time-resolved kinetic study on the effect of trifluoroacetic acid (TFA) on the
      hydrogen atom transfer (HAT) reactions from 1,n-alkanediamines (R2N(CH2)nNR2, R =
      H, CH3; n = 1-4), piperazine, and 1,4-dimethylpiperazine to the cumyloxyl radical
      (CumO(*)), has been carried out in MeCN and DMSO. Very strong deactivation of the
      alpha-C-H bonds has been observed following nitrogen protonation and the results
      obtained have been explained in terms of substrate basicity, of the distance
      between the two basic centers and of the solvent hydrogen bond acceptor ability.
      At [substrate] <= 1/2 [TFA] the substrates exist in the doubly protonated form
      HR2N(+)(CH2)nN(+)R2H, and no reaction with CumO(*) is observed. At 1/2 [TFA] <
      [substrate] <= [TFA], HAT occurs from the C-H bonds that are alpha to the
      nonprotonated nitrogen in R2N(CH2)nN(+)R2H. At [substrate] > [TFA], HAT occurs
      from the alpha-C-H bonds of R2N(CH2)nNR2, and the mesured kH values are very
      close to those obtained in the absence of TFA. Comparison between MeCN and DMSO
      clearly shows that in the monoprotonated diamines R2N(CH2)nN(+)R2H remote C-H
      deactivation can be modulated through solvent hydrogen bonding. 

PMID- 24869918
TI  - Energy efficiency and greenhouse gas emission intensity of petroleum products at
      U.S. refineries.
AB  - This paper describes the development of (1) a formula correlating the variation
      in overall refinery energy efficiency with crude quality, refinery complexity,
      and product slate; and (2) a methodology for calculating energy and greenhouse
      gas (GHG) emission intensities and processing fuel shares of major U.S. refinery
      products. Overall refinery energy efficiency is the ratio of the energy present
      in all product streams divided by the energy in all input streams. Using linear
      programming (LP) modeling of the various refinery processing units, we analyzed
      43 refineries that process 70% of total crude input to U.S. refineries and cover
      the largest four Petroleum Administration for Defense District (PADD) regions (I,
      II, III, V). Based on the allocation of process energy among products at the
      process unit level, the weighted-average product-specific energy efficiencies
      (and ranges) are estimated to be 88.6% (86.2%-91.2%) for gasoline, 90.9% (84.8%
      94.5%) for diesel, 95.3% (93.0%-97.5%) for jet fuel, 94.5% (91.6%-96.2%) for
      residual fuel oil (RFO), and 90.8% (88.0%-94.3%) for liquefied petroleum gas
      (LPG). The corresponding weighted-average, production GHG emission intensities
      (and ranges) (in grams of carbon dioxide-equivalent (CO2e) per megajoule (MJ))
      are estimated to be 7.8 (6.2-9.8) for gasoline, 4.9 (2.7-9.9) for diesel, 2.3
      (0.9-4.4) for jet fuel, 3.4 (1.5-6.9) for RFO, and 6.6 (4.3-9.2) for LPG. The
      findings of this study are key components of the life-cycle assessment of GHG
      emissions associated with various petroleum fuels; such assessment is the
      centerpiece of legislation developed and promulgated by government agencies in
      the United States and abroad to reduce GHG emissions and abate global warming. 

PMID- 24869920
TI  - 3D visualization of inhomogeneous multi-layered structure and Young's modulus of
      the solid electrolyte interphase (SEI) on silicon anodes for lithium ion
      batteries.
AB  - The microstructure and mechanical properties of the solid electrolyte interphase
      (SEI) in non-aqueous lithium ion batteries are key issues for understanding and
      optimizing the electrochemical performance of lithium batteries. In this report,
      the three-dimensional (3D) multi-layered structures and the mechanical properties
      of the SEI formed on a silicon anode material for next generation lithium ion
      batteries have been visualized directly for the first time, through a scanning
      force spectroscopy method. The coverage of the SEI on silicon anodes is also
      obtained through 2D projection plots. The effects of temperature and the function
      of additives in the electrolyte on the SEI can be understood accordingly. A
      modified model about dynamic evolution of the SEI on the silicon anode material
      is also proposed, which aims to explain why the SEI is very thick and how the
      multi-layered structure is formed and decomposed dynamically. 

PMID- 24869921
TI  - Reactivity of silver clusters anions with ethanethiol.
AB  - We have investigated the gas-phase reactivity of silver clusters with ethanethiol
      in a fast-flow tube reactor. The primary cluster products observed in this
      reaction are AgnSH(-) and AgnSH2(-), indicating C-S bond activation, together
      with interesting byproducts H3S(-) and (H3S)2(-). Agn(-) clusters with an odd
      number of valence electrons (n = even) were observed to be more reactive than
      those with an even number of electrons-a feature previously only observed in the
      reactivity of Agn(-) with triplet oxygen, indicating that radical active sites
      play a role in their reactivity. Furthermore, the reactivity dramatically
      increases with large flow rate of ethanethiol being introduced in the flow tube.
      Theoretical investigations on the reactivity of Ag13(-) and Ag8(-) with
      ethanethiol indicate that both Ag13(-) and Ag8(-) face significant barriers to
      reactivity with a single ethanethiol molecule. However, Ag8(-) reacts readily in
      a cooperative reaction with two ethanethiol molecules, consistent with the
      dramatic increase in reactivity with a large flow rate. Further hydrogen-transfer
      reactions may then release an ethylene molecule or an ethyl radical resulting in
      the observed AgnSH(-) species. 

PMID- 24869919
TI  - N-terminus of the protein kinase CLK1 induces SR protein hyperphosphorylation.
AB  - SR proteins are essential splicing factors that are regulated through multisite
      phosphorylation of their RS (arginine/serine-rich) domains by two major families
      of protein kinases. The SRPKs (SR-specific protein kinases) efficiently
      phosphorylate the arginine/serine dipeptides in the RS domain using a conserved
      docking groove in the kinase domain. In contrast, CLKs (Cdc2-like kinases) lack a
      docking groove and phosphorylate both arginine/serine and serine-proline
      dipeptides, modifications that generate a hyperphosphorylated state important for
      unique SR protein-dependent splicing activities. All CLKs contain long flexible N
      terminal extensions (140-300 residues) that resemble the RS domains present in
      their substrate SR proteins. We showed that the N-terminus in CLK1 contacts both
      the kinase domain and the RS domain of the SR protein SRSF1 (SR protein splicing
      factor 1). This interaction not only is essential for facilitating
      hyperphosphorylation, but also induces co-operative binding of SRSF1 to RNA. The
      N-terminus of CLK1 enhances the total phosphoryl contents of a panel of
      physiological substrates including SRSF1, SRSF2, SRSF5 and Tra2beta1 (transformer
      2beta1) by 2-3-fold. These findings suggest that CLK1-dependent
      hyperphosphorylation is the result of a general mechanism in which the N-terminus
      acts as a bridge connecting the kinase domain and the RS domain of the SR
      protein. 

PMID- 24869922
TI  - Evolution of fairness in the not quite ultimatum game.
AB  - The Ultimatum Game (UG) is an economic game where two players (proposer and
      responder) decide how to split a certain amount of money. While traditional
      economic theories based on rational decision making predict that the proposer
      should make a minimal offer and the responder should accept it, human subjects
      tend to behave more fairly in UG. Previous studies suggested that extra
      information such as reputation, empathy, or spatial structure is needed for
      fairness to evolve in UG. Here we show that fairness can evolve without
      additional information if players make decisions probabilistically and may
      continue interactions when the offer is rejected, which we call the Not Quite
      Ultimatum Game (NQUG). Evolutionary simulations of NQUG showed that the
      probabilistic decision making contributes to the increase of proposers' offer
      amounts to avoid rejection, while the repetition of the game works to responders'
      advantage because they can wait until a good offer comes. These simple extensions
      greatly promote evolution of fairness in both proposers' offers and responders'
      acceptance thresholds. 

PMID- 24869923
TI  - Singlet oxygen-mediated synthesis of bis-spiroketals found in azaspiracids.
AB  - Conversion of a simple furan into the ABCD-ring skeleton of the azaspiracids via
      a singlet oxygen-initiated one-pot process has been accomplished. 

PMID- 24869924
TI  - Nerve proximity during bicortical drilling for subpectoral biceps tenodesis: a
      cadaveric study.
AB  - PURPOSE: The long head of the biceps can develop tendonitis and tendinosis, which
      can lead to pain in the bicipital groove. The use of bicortical button fixation
      allows for a smaller defect in the humerus compared with tenodesis screws,
      reducing the risk of fracture. Our objective is to evaluate the exit location of
      our bicortical button and its relation to relevant posterior nervous structures.
      METHODS: We performed anatomic dissection of 6 fresh-frozen cadaveric upper
      extremities. At the level of the inferior border of the pectoralis major tendon,
      the musculotendinous junction of the long head of the biceps was identified. At
      the base of the bicipital groove, a 3.2-mm guidewire was advanced perpendicularly
      through both the anterior and posterior cortex. Posteriorly, the radial and
      axillary nerves were carefully dissected. For each dissection, we recorded the
      closest distance from the posterior cortical hole created by our drill to both
      the axillary and radial nerves using digital calipers. RESULTS: The mean distance
      from the axillary nerve to the posterior drill hole was 25.1 mm (95% confidence
      interval, 21.6 to 28.6 mm). The mean distance from the radial nerve to the
      posterior drill hole was 30.3 mm (95% confidence interval, 27.2 to 33.4 mm).
      CONCLUSIONS: With placement of the tenodesis at the inferior aspect of the
      bicipital groove in conjunction with the musculotendinous junction, open
      subpectoral tenodesis of the long head of the biceps can be performed using
      bicortical button fixation without risk to the posterior nervous structures.
      CLINICAL RELEVANCE: This cadaveric study suggests that posterior proximal humerus
      nervous structures can be avoided with proper tenodesis placement.

PMID- 24869927
TI  - Efficient synthesis of fluorescent-PET probes based on [18F]BODIPY dye.
AB  - We report the direct conversion of fluorescent probes to PET/fluorescent probes
      after efficient [(19)F]/[(18)F] exchange at the BODIPY motif. The radiolabeling
      of a NIR BODIPY dye was also established, which was conjugated with the RGD
      peptide for PET/fluorescence imaging of integrin expression in vivo. 

PMID- 24869926
TI  - Incidence and management of hip dislocation in tumour patients with a modular
      prosthesis of the proximal femur.
AB  - PURPOSE: Little data is available about the incidence and especially the
      management of hip dislocation following the implantation of modular tumor
      prostheses of the proximal femur. In this retrospective single-centre study we
      assessed the incidence of hip dislocation following implantation of a proximal
      femoral modular prosthesis as well as the success of the subsequent surgical or
      non-surgical treatment in tumor patients. METHODS: Between 1982 and 2008, 166
      tumor patients received a modular prosthesis of the proximal femur at our
      institution. The average age at the time of surgery was 50 +/- 20 years (range,
      six to 84 years). An additional pelvic reconstruction was done in 14 patients. An
      artificial band for soft tissue reconstruction of the hip was used in 19
      patients. The average time of follow-up was 46 +/- 64 months (range, one to 277
      months). RESULTS: The overall dislocation rate after proximal femoral replacement
      was 13% after a mean time of seven +/- eight months (range, 0.3-33 months) after
      surgery. Between 1982 and 1986 the dislocation rate was 33% and declined to 9% in
      subsequent years (1987-2008). Patients who had received an additional pelvic
      reconstruction had a three fold higher dislocation rate (p <0.05). Patients with
      closed reduction had a 58% (eight of 12) re-dislocation rate compared to 11% (one
      of nine) for open reduction (p = 0.0357). CONCLUSIONS: Dislocation of a modular
      prosthesis of the proximal femur is a common complication, especially in cases
      with additional pelvic resection with extensive bone and soft-tissue defects.
      Open surgical management may be more effective in preventing re-dislocation than
      closed reduction and bracing alone.

PMID- 24869928
TI  - i-motif-driven Au nanomachines in programmed siRNA delivery for gene-silencing
      and photothermal ablation.
AB  - The present work illustrates unique design, construction and operation of an i
      motif-based DNA nanomachine templated on gold nanoparticles (AuNPs), which
      utilizes pH-responsive dynamic motion of i-motif DNA strands and aggregational
      behavior of AuNPs to elicit programmed delivery of therapeutic siRNA. The pH
      sensitive nucleic acids immobilized on the AuNPs consisted of three functional
      segments, i.e., an i-motif DNA, an overhanging linker DNA and a therapeutic
      siRNA. At neutral pH, the i-motif DNA is hybridized with the overhanging linker
      DNA segment of the therapeutic siRNA. However, in endosomal acidic pH, the i
      motif DNA forms interstrand tetraplex, which could induce cluster formation of
      AuNPs resulting in endosomal escape of AuNP clusters, and produce a high gene
      silencing efficiency by releasing siRNA in the cytosol. Furthermore, the cluster
      formation of AuNPs accelerated photothermal ablation of cells when irradiated
      with laser. Precise and synchronized biomechanical motion in subcellular
      microenvironment is realized through judicious integration of pH-responsive
      behavior of the i-motif DNA and AuNPs, and meticulous designing of DNA. 

PMID- 24869925
TI  - Neural networks related to dysfunctional face processing in autism spectrum
      disorder.
AB  - One of the most consistent neuropsychological findings in autism spectrum
      disorders (ASD) is a reduced interest in and impaired processing of human faces.
      We conducted an activation likelihood estimation meta-analysis on 14 functional
      imaging studies on neural correlates of face processing enrolling a total of 164
      ASD patients. Subsequently, normative whole-brain functional connectivity maps
      for the identified regions of significant convergence were computed for the task
      independent (resting-state) and task-dependent (co-activations) state in healthy
      subjects. Quantitative functional decoding was performed by reference to the
      BrainMap database. Finally, we examined the overlap of the delineated network
      with the results of a previous meta-analysis on structural abnormalities in ASD
      as well as with brain regions involved in human action observation/imitation. We
      found a single cluster in the left fusiform gyrus showing significantly reduced
      activation during face processing in ASD across all studies. Both task-dependent
      and task-independent analyses indicated significant functional connectivity of
      this region with the temporo-occipital and lateral occipital cortex, the inferior
      frontal and parietal cortices, the thalamus and the amygdala. Quantitative
      reverse inference then indicated an association of these regions mainly with face
      processing, affective processing, and language-related tasks. Moreover, we found
      that the cortex in the region of right area V5 displaying structural changes in
      ASD patients showed consistent connectivity with the region showing aberrant
      responses in the context of face processing. Finally, this network was also
      implicated in the human action observation/imitation network. In summary, our
      findings thus suggest a functionally and structurally disturbed network of
      occipital regions related primarily to face (but potentially also language)
      processing, which interact with inferior frontal as well as limbic regions and
      may be the core of aberrant face processing and reduced interest in faces in ASD.

PMID- 24869929
TI  - Current status of gene expression profiling to assist decision making in stage II
      colon cancer.
AB  - The decision regarding adjuvant therapy for patients with stage II colon cancer
      remains a challenge. In contrast to stage III colon cancer, for which compelling
      clinical data support the use of adjuvant chemotherapy, the clinical benefit of
      systemic therapy in unselected patients with stage II disease is modest at best.
      Risk stratification based on clinicopathologic features and DNA mismatch repair
      status is commonly used in adjuvant therapy decisions, but these factors do not
      have a desired level of precision in identifying patients at high risk. Recently,
      gene expression platforms have been developed to further define risk and to
      assist in therapeutic decision making for patients with stage II disease. This
      review describes those platforms that are furthest along in clinical development,
      in an effort to place their potential clinical application in context. 

PMID- 24869930
TI  - Prognostic value of interim positron emission tomography in patients with
      peripheral T-cell lymphoma.
AB  - The definition of the role of positron emission tomography (PET) in peripheral T
      cell lymphomas (PTCLs) is still under investigation. The purpose of the present
      observational retrospective study was to assess the early prognostic value of PET
      after the first three cycles of therapy (PET+3), evaluating visual data in de
      novo PTCL patients treated in first line with standard chemotherapy and followed
      by both PET and computed tomography scan. Of 27 PET+3-negative patients, 19 also
      had a negative PET at the end of treatment (PET+6), whereas 8 of 27 had a
      positive final one; 6 of 7 PET+3-positive patients had a positive PET+6, whereas
      only 1 patient had a negative PET+6. Estimated overall survival plotted according
      to PET+3 results showed 78.6% for negative patients and 21.4% for positive
      patients at 88.7 months with a significant difference. Patients with negative
      PET+3 had superior progression-free survival of 72.6% compared with 16.7% of
      PET+3-positive patients. At the time of this analysis, 17 of 19 (89.5%) patients
      with negative PET+3 are in continuous complete response (CCR) and only 1 of 7
      (14.2%) patients with positive PET+3 is still in CCR. In conclusion, our results
      indicate that positive PET+3 is predictive of a worse outcome in PTCL, and this
      significant statistical difference between the two curves could be clinically
      informative. Larger and prospective studies and harmonization of PET reading
      criteria are needed. 

PMID- 24869931
TI  - Safety profile of Pertuzumab with Trastuzumab and Docetaxel in patients from Asia
      with human epidermal growth factor receptor 2-positive metastatic breast cancer:
      results from the phase III trial CLEOPATRA.
AB  - INTRODUCTION: We report detailed safety analyses by geographic region from the
      phase III study CLEOPATRA with pertuzumab, trastuzumab, and docetaxel in patients
      with human epidermal growth factor receptor 2 (HER2)-positive first-line
      metastatic breast cancer. PATIENTS AND METHODS: Patients received
      pertuzumab/placebo at 840 mg in cycle 1 and 420 mg in subsequent cycles, and
      trastuzumab at 8 mg/kg in cycle 1 and 6 mg/kg in subsequent cycles; docetaxel was
      initiated at 75 mg/m(2). All study drugs were given intravenously, 3 times
      weekly. RESULTS: Docetaxel dose reductions below 75 mg/m(2) were more common in
      patients from Asia (47.0%) than other regions (13.4%); docetaxel dose escalations
      to 100 mg/m(2) were less frequent in Asia (2.4%) than other regions (18.7%).
      Rates of edema (26.1% and 5.4% for Asia and other regions, respectively), myalgia
      (42.3%, 14.7%), nail disorder (39.9%, 15.1%), febrile neutropenia (18.6%, 7.1%),
      upper respiratory tract infection (25.7%, 10.2%), decreased appetite (47.0%,
      19.1%), and rash (44.3%, 22.0%) were at least twice as high in Asia as in other
      regions. Adverse events did not result in a reduction in the median number of
      study treatment cycles administered in patients from Asia. Efficacy analyses per
      region showed hazard ratios similar to those of the whole intention-to-treat
      (ITT) population for progression-free survival (ITT: 0.63; Asia: 0.68; other
      regions: 0.61) and overall survival (ITT: 0.66; Asia: 0.64; other regions: 0.66).
      CONCLUSION: Despite a higher proportion of docetaxel dose reductions in patients
      from Asia, survival benefits were comparable between regions. The benefit-risk
      profile of pertuzumab, trastuzumab, and docetaxel supports this regimen as the
      first-line therapy for patients with HER2-positive metastatic breast cancer from
      all geographic regions.

PMID- 24869932
TI  - Dual-regulated lentiviral vector for gene therapy of X-linked chronic
      granulomatosis.
AB  - Regulated transgene expression may improve the safety and efficacy of
      hematopoietic stem cell (HSC) gene therapy. Clinical trials for X-linked chronic
      granulomatous disease (X-CGD) employing gammaretroviral vectors were limited by
      insertional oncogenesis or lack of persistent engraftment. Our novel strategy,
      based on regulated lentiviral vectors (LV), targets gp91(phox) expression to the
      differentiated myeloid compartment while sparing HSC, to reduce the risk of
      genotoxicity and potential perturbation of reactive oxygen species levels.
      Targeting was obtained by a myeloid-specific promoter (MSP) and
      posttranscriptional, microRNA-mediated regulation. We optimized both components
      in human bone marrow (BM) HSC and their differentiated progeny in vitro and in a
      xenotransplantation model, and generated therapeutic gp91(phox) expressing LVs
      for CGD gene therapy. All vectors restored gp91(phox) expression and function in
      human X-CGD myeloid cell lines, primary monocytes, and differentiated myeloid
      cells. While unregulated LVs ectopically expressed gp91(phox) in CD34(+) cells,
      transcriptionally and posttranscriptionally regulated LVs substantially reduced
      this off-target expression. X-CGD mice transplanted with transduced HSC restored
      gp91(phox) expression, and MSP-driven vectors maintained regulation during BM
      development. Combining transcriptional (SP146.gp91-driven) and
      posttranscriptional (miR-126-restricted) targeting, we achieved high levels of
      myeloid-specific transgene expression, entirely sparing the CD34(+) HSC
      compartment. This dual-targeted LV construct represents a promising candidate for
      further clinical development. 

PMID- 24869933
TI  - Overcoming the cystic fibrosis sputum barrier to leading adeno-associated virus
      gene therapy vectors.
AB  - Gene therapy has not yet improved cystic fibrosis (CF) patient lung function in
      human trials, despite promising preclinical studies. In the human CF lung,
      inhaled gene vectors must penetrate the viscoelastic secretions coating the
      airways to reach target cells in the underlying epithelium. We investigated
      whether CF sputum acts as a barrier to leading adeno-associated virus (AAV) gene
      vectors, including AAV2, the only serotype tested in CF clinical trials, and
      AAV1, a leading candidate for future trials. Using multiple particle tracking, we
      found that sputum strongly impeded diffusion of AAV, regardless of serotype, by
      adhesive interactions and steric obstruction. Approximately 50% of AAV vectors
      diffused >1,000-fold more slowly in sputum than in water, with large patient-to
      patient variation. We thus tested two strategies to improve AAV diffusion in
      sputum. We showed that an AAV2 mutant engineered to have reduced heparin binding
      diffused twice as fast as AAV2 on average, presumably because of reduced adhesion
      to sputum. We also discovered that the mucolytic N-acetylcysteine could markedly
      enhance AAV diffusion by altering the sputum microstructure. These studies
      underscore that sputum is a major barrier to CF gene delivery, and offer
      strategies for increasing AAV penetration through sputum to improve clinical
      outcomes. 

PMID- 24869934
TI  - Carotid artery intima-media thickness and erectile dysfunction in patients with
      metabolic syndrome.
AB  - BACKGROUND: Metabolic syndrome (MS) has become a pandemic in Turkey, as is the
      case globally. Increase in carotid artery intima-media thickness (CIMT) and
      erectile dysfunction (ED) may be evident before the clinical signs of
      cardiovascular disease appear. We aimed to investigate the prevalence of
      increased CIMT and ED as markers of atherosclerotic disease in patients with MS.
      MATERIAL AND METHODS: Thirty-two patients with MS and 29 healthy controls were
      included. Anthropometric and biochemical parameters, along with total
      testosterone (TT), high sensitive C-reactive protein (hs-CRP), were recorded.
      Carotid artery intima-media thickness was measured. Erectile dysfunction was
      assessed with International Index of Erectile Function. RESULTS: Patients with MS
      had higher BMI, fasting plasma glucose, post-prandial plasma glucose, insulin,
      HOMA-IR, total cholesterol, triglycerides, hs-CRP, and CIMT, whereas TT levels
      were lower (p<0.0001). The prevalence and severity of erectile dysfunction were
      higher in patients with MS (p<0.0001). Erectile dysfunction scores correlated
      inversely with CIMT. MS patients with ED were older and had higher CIMT compared
      to those without ED. Increase in age and HOMA and decrease in TT increased the
      risk of ED. When KIMT exceeding the 95th percentile of healthy controls was
      accepted as a risk factor for CVD, presence of ED was the only determinant for
      this increase. CONCLUSIONS: Erectile dysfunction was more prevalent and severe in
      patients with MS and correlated with subclinical endothelial dysfunction. Total
      testosterone deficiency was prominent among MS patients. Presence of ED points to
      an increased risk of cardiovascular disease when MS is present.

PMID- 24869935
TI  - Muscleblind-like 1 (Mbnl1) regulates pre-mRNA alternative splicing during
      terminal erythropoiesis.
AB  - The scope and roles of regulated isoform gene expression during erythroid
      terminal development are poorly understood. We identified hundreds of
      differentiation-associated isoform changes during terminal erythropoiesis.
      Sequences surrounding cassette exons of skipped exon events are enriched for
      motifs bound by the Muscleblind-like (MBNL) family of splicing factors. Knockdown
      of Mbnl1 in cultured murine fetal liver erythroid progenitors resulted in a
      strong block in erythroid differentiation and disrupted the developmentally
      regulated exon skipping of Ndel1 mRNA, which is bound by MBNL1 and critical for
      erythroid terminal proliferation. These findings reveal an unanticipated scope of
      the alternative splicing program and the importance of Mbnl1 during erythroid
      terminal differentiation. 

PMID- 24869936
TI  - New insights into the spatiotemporal localization of prothrombinase in vivo.
AB  - The membrane-dependent interaction of factor Xa (FXa) with factor Va (FVa) forms
      prothrombinase and drives thrombin formation essential for hemostasis. Activated
      platelets are considered to provide the primary biological surface to support
      prothrombinase function. However, the question of how other cell types may
      cooperate within the biological milieu to affect hemostatic plug formation
      remains unaddressed. We used confocal fluorescence microscopy to image the
      distribution of site-specific fluorescent derivatives of FVa and FXa after laser
      injury in the mouse cremaster arteriole. These proteins bound to the injury site
      extend beyond the platelet mass to the surrounding endothelium. Although bound
      FVa and FXa may have been present on the platelet core at the nidus of the
      injury, bound proteins were not evident on platelets adherent even a small
      distance from the injury site. Manipulations to drastically reduce adherent
      platelets yielded a surprisingly modest decrease in bound FXa and FVa with little
      impact on fibrin formation. Thus, platelets adherent to the site of vascular
      injury do not play the presumed preeminent role in supporting prothrombinase
      assembly and thrombin formation. Rather, the damaged/activated endothelium and
      possibly other blood cells play an unexpectedly important role in providing a
      procoagulant membrane surface in vivo. 

PMID- 24869938
TI  - How we evaluate and treat neutropenia in adults.
AB  - Isolated neutropenia is a common clinical problem seen by primary care physicians
      and hematologists. The evaluation of neutropenia is dictated by the acuity of the
      clinical presentation and the duration, age, and clinical status of the patient.
      In this review, we provide a practical approach to the evaluation of the adult
      patient with neutropenia, with the major focus on the evaluation of neutropenia
      in the outpatient setting. 

PMID- 24869937
TI  - Dissection of vertebrate hematopoiesis using zebrafish thrombopoietin.
AB  - In nonmammalian vertebrates, the functional units of hemostasis are thrombocytes.
      Thrombocytes are thought to arise from bipotent thrombocytic/erythroid
      progenitors (TEPs). TEPs have been experimentally demonstrated in avian models of
      hematopoiesis, and mammals possess functional equivalents known as
      megakaryocyte/erythroid progenitors (MEPs). However, the presence of TEPs in
      teleosts has only been speculated. To identify and prospectively isolate TEPs, we
      identified, cloned, and generated recombinant zebrafish thrombopoietin (Tpo). Tpo
      mRNA expanded itga2b:GFP(+) (cd41:GFP(+)) thrombocytes as well as hematopoietic
      stem and progenitor cells (HSPCs) in the zebrafish embryo. Utilizing Tpo in
      clonal methylcellulose assays, we describe for the first time the prospective
      isolation and characterization of TEPs from transgenic zebrafish. Combinatorial
      use of zebrafish Tpo, erythropoietin, and granulocyte colony stimulating factor
      (Gcsf) allowed the investigation of HSPCs responsible for erythro-, myelo-, and
      thrombo-poietic differentiation. Utilizing these assays allowed the visualization
      and differentiation of hematopoietic progenitors ex vivo in real-time with time
      lapse and high-throughput microscopy, allowing analyses of their clonogenic and
      proliferative capacity. These studies indicate that the functional role of Tpo in
      the differentiation of thrombocytes from HSPCs is well conserved among vertebrate
      organisms, positing the zebrafish as an excellent model to investigate diseases
      caused by dysregulated erythro- and thrombo-poietic differentiation. 

PMID- 24869940
TI  - Stable long-term mixed chimerism achieved in a canine model of allogeneic in
      utero hematopoietic cell transplantation.
AB  - Evidence supporting the efficacy of in utero hematopoietic cell transplantation
      (IUHCT) in a valid large animal model is needed prior to clinical application.
      The objective of this study was to establish clinically relevant levels of
      hematopoietic chimerism in a canine model of maternal-to-fetal IUHCT. We first
      assessed immune and hematopoietic ontogeny relevant to IUHCT in the canine model
      and identified 40 days' gestation (term 63 days) as a time point at the
      initiation of thymic selection, and prior to bone marrow hematopoiesis, that
      might be optimal for IUHCT. We next determined that intravascular administration
      of donor cells via intracardiac injection was far more efficient and resulted in
      much higher levels of donor cell engraftment than intraperitoneal injection. By
      applying these findings, we achieved stable long-term multilineage engraftment in
      21 of 24 surviving recipients with an average level of initial chimerism of 11.7%
      (range 3% to 39%) without conditioning or evidence of graft-versus-host disease.
      Donor cell chimerism remained stable for up to 2 years and was associated with
      donor-specific tolerance for renal transplantation. The levels of donor cell
      chimerism achieved in this study would be therapeutic for many hematopoietic
      disorders and are supportive of a clinical trial of IUHCT. 

PMID- 24869939
TI  - The orally bioavailable MDM2 antagonist RG7112 and pegylated interferon alpha 2a
      target JAK2V617F-positive progenitor and stem cells.
AB  - The Philadelphia chromosomal-negative chronic myeloproliferative neoplasms (MPNs)
      originate at the level of the hematopoietic stem cell (HSC). The protracted
      clinical course of the MPNs has limited the use of potentially toxic treatment
      modalities, which may eliminate the responsible malignant clone. Treatment with
      low doses of RG7112, an orally available small-molecule inhibitor of p53-MDM2,
      both alone and combined with pegylated interferon alpha 2a (Peg-IFNalpha 2a),
      significantly decreased MPN colony-forming unit-granulocyte macrophage and burst
      forming unit-erythroid numbers and preferentially eliminated the total number of
      JAKV617F(+) MPN hematopoietic progenitor cells. The effects of RG7112 and Peg
      IFNalpha 2a on MPN progenitor cells were dependent on blocking p53-MDM2
      interactions and activating the p53 pathway, thereby increasing MPN CD34(+) cell
      apoptosis. Treatment of polycythemia vera (PV) and primary myelofibrosis (PMF)
      CD34(+) cells with low doses of RG7112 and Peg-IFNalpha 2a before their
      transplantation into immune-deficient mice decreased the degree of donor-derived
      chimerism as well as the JAK2V617F allele burden, indicating that these drugs can
      each alone or in combination deplete MPN HSCs. These results provide a rationale
      for the use of combinations of low doses of RG7112 and Peg-IFNalpha 2a for the
      treatment of PV or PMF patients with the intent of altering their natural
      history. 

PMID- 24869941
TI  - Preemptive rituximab infusions after remission efficiently prevent relapses in
      acquired thrombotic thrombocytopenic purpura.
AB  - In acquired thrombotic thrombocytopenic purpura (TTP), the persistence of severe
      ADAMTS13 deficiency (<10%) during remission is associated with more relapse.
      Preemptive (ie, after remission) administration of rituximab in these patients to
      prevent relapses remains controversial. We performed a cross-sectional analysis
      of 12-year follow-up data to compare the relapse incidence with or without
      preemptive rituximab infusion. Among 48 patients who experienced at least one
      episode of acquired TTP followed by severe ADAMTS13 deficiency during remission,
      30 received preemptive rituximab (group 1); the other 18 did not (group 2). After
      a median of 17 months (interquartile range [IQR], 11-29) following rituximab, the
      relapse incidence decreased from 0.57 episodes/year (IQR, 0.46-0.7) to 0
      episodes/year (IQR, 0-0.81) (P < .01) in group 1. ADAMTS13 activity 3 months
      after the first rituximab infusion increased to 46% (IQR, 30%-68%). Nine patients
      required additional courses of rituximab. In 5 patients, ADAMTS13 activity failed
      to increase durably. Four patients experienced manageable adverse effects. In
      group 2, the relapse incidence was higher (0.5 relapses/year; IQR, 0.12-0.5; P <
      .01). Relapse-free survival was longer in group 1 (P = .049). A persistent severe
      ADAMTS13 deficiency during TTP remission should prompt consideration of
      preemptive rituximab to prevent relapses. 

PMID- 24869942
TI  - HLA-haploidentical stem cell transplantation after removal of alphabeta+ T and B
      cells in children with nonmalignant disorders.
AB  - Twenty-three children with nonmalignant disorders received HLA-haploidentical
      hematopoietic stem cell transplantation (haplo-HSCT) after ex vivo elimination of
      alphabeta(+) T cells and CD19(+) B cells. The median number of CD34(+),
      alphabeta(+)CD3(+), and B cells infused was 16.8 * 10(6), 40 * 10(3), and 40 *
      10(3) cells/kg, respectively. No patient received any posttransplantation
      pharmacologic prophylaxis for graft-versus-host disease (GVHD). All but 4
      patients engrafted, these latter being rescued by a second allograft. Three
      patients experienced skin-only grade 1 to 2 acute GVHD. No patient developed
      visceral acute or chronic GVHD. Cumulative incidence of transplantation-related
      mortality was 9.3%. With a median follow-up of 18 months, 21 of 23 children are
      alive and disease-free, the 2-year probability of disease-free survival being
      91.1%. Recovery of gammadelta(+) T cells was prompt, but alphabeta(+) T cells
      progressively ensued over time. Our data suggest that this novel graft
      manipulation strategy is safe and effective for haplo-HSCT. This trial was
      registered at www.clinicaltrials.gov as #NCT01810120. 

PMID- 24869943
TI  - Pre-referral rectal artesunate for severe malaria.
AB  - BACKGROUND: Severe or complicated malaria is a medical emergency and people die
      as a result of delays in starting treatment. Most patients need parenteral
      treatment, and in primary healthcare facilities, where intravenous therapy is not
      available but intramuscular injections can be given, intramuscular quinine,
      artesunate, and artemether have been used before transporting patients to
      hospital.However, in rural settings with limited access to health care,
      intramuscular injections may also be unavailable. In these situations, rectal
      artesunate given prior to transfer to hospital by volunteers with little medical
      training, may be a feasible option. OBJECTIVES: To evaluate the effects of pre
      referral treatment with rectal artesunate on mortality and morbidity in people
      with severe malaria. SEARCH METHODS: We searched the Cochrane Central Register of
      Controlled Trials (CENTRAL) published in The Cochrane Library; MEDLINE; EMBASE
      and LILACS up to 21 May 2014. We also searched the WHO clinical trial registry
      platform and the metaRegister of Controlled Trials (mRCT) for ongoing trials.
      SELECTION CRITERIA: Individual or cluster-randomized controlled trials comparing
      pre-referral rectal artesunate with placebo or injectable antimalarials in
      children and children with severe malaria. DATA COLLECTION AND ANALYSIS: Two
      authors independently screened titles and abstracts for potentially eligible
      trials, and extracted data from the included trials. Dichotomous outcomes were
      summarized using risk ratios (RR) and presented with 95% confidence intervals
      (95% CI). Where data allowed, we conducted subgroup analyses by age, trial region
      and whether participants were included in the trial analysis. We assessed the
      quality of evidence for the most important outcomes using the GRADE approach.
      MAIN RESULTS: One trial met the inclusion criteria; a placebo-controlled trial of
      17,826 children and adults living in rural villages in Ghana and Tanzania
      (Africa) and Bangladesh (Asia). Villagers with no previous medical training were
      trained to recognize the symptoms of severe malaria, administer rectal artesunate
      and refer patients to hospital. The trained villagers were supervised during the
      trial period. In the African sites only children aged 6 to 72 months were
      enrolled, whereas in Bangladesh, older children and adults were also enrolled.In
      young children (aged 6 to 72 months) there were fewer deaths following rectal
      artesunate than with placebo (RR 0.74; 95% CI 0.59 to 0.93; one trial; 8050
      participants; moderate quality evidence), while in older children and adults
      there were more deaths in those given rectal artesunate (RR 2.21; 95% CI 1.18 to
      4.15; one trial; 4018 participants; low quality evidence).In Africa, only 56% of
      participants reached a secondary healthcare facility within six hours compared to
      over 90% in Asia. There were no differences between the intervention and control
      groups in the proportion of participants reaching a healthcare facility within
      six hours (RR 0.99; 95% CI 0.98 to 1.01; 12,068 participants), or in the
      proportion with parasitaemia (RR 1.00; 95% CI 0.98 to 1.02; 17,826 participants),
      or with coma or convulsions on arrival (RR 1.01; 95% CI 0.90 to 1.14; 12,068
      participants).There are no existing trials that compare rectal versus
      intramuscular artesunate. AUTHORS' CONCLUSIONS: In rural areas without access to
      injectable antimalarials rectal artesunate provided before transfer to a referral
      facility probably reduces mortality in severely ill young children compared to
      referral without treatment. However, the unexpected finding of possible higher
      mortality in older children and adults has to be taken into account in forming
      any national or local policies about pre-referral rectal artesunate.

PMID- 24869944
TI  - Determination of domperidone in human plasma using high performance liquid
      chromatography with fluorescence detection for clinical application.
AB  - A simple and reliable method for the determination of domperidone in human plasma
      has been developed. Plasma samples (1mL) were pre-purified by a solid-phase
      extraction with Bond Elut((r)) C18. The separation was achieved with XBridgeTM
      C18 column (150mm*4.6mm i.d., 5MUm) at 40 degrees C. The mobile phase was a
      mixture of acetonitrile and 10mM ammonium acetate buffer (36:64, v/v), adjusted
      to pH 9.4 with 20% ammonium solution at a flow rate of 1.0mL/min. The peak was
      detected using fluorescence detector at excitation 282nm and emission 328nm.
      Retention times for domperidone and internal standard (propranolol) were 8.3min
      and 11.2min, respectively. The method showed a good linearity (r>0.999),
      precision (relative standard deviations <10.6%), and extraction recovery (85.7
      99.7%) over a concentration of 1-100ng/mL. The lower limit of quantification
      (LLOQ) was 1.0ng/mL. This proposed method was successfully applied to a
      pharmacokinetic interaction study of domperidone in healthy Japanese volunteers. 

PMID- 24869945
TI  - Highly sensitive, selective and rapid LC-MS method for simultaneous
      quantification of diadenosine polyphosphates in human plasma.
AB  - BACKGROUND: Diadenosine polyphosphates (ApnAs) are endogenous mediators involved
      in large number of physiologic and pathophysiologic processes. The quantification
      of diadenosine polyphosphates in plasma and biological matrices is still
      challenging. Therefore, there is an urgent need for a simple and reliable
      quantification method suitable for clinical studies. The classical quantification
      of diadenosine polyphosphates is based on chromatographic separation and UV
      adsorption of the resulting fractions. These procedures are associated with low
      selectivity due to co-eluting plasma components. Therefore, we developed and
      validated a highly sensitive, selective and rapid LC-ESI-MS method for
      simultaneous quantification of ApnAs (with n=3-6) in human plasma within this
      study. The identities of the endogenous ApnAs (with n=3-6) were revealed by
      comparison of ESI-MS/MS fragment spectra of isolated endogenous compounds with
      those of authentic ApnAs. METHODS: Diadenosine polyphosphates were extracted from
      100MUl human plasma using weak anion-exchange extraction cartridges. The
      separation of ApnAs was achieved using capillary C18 columns. ESI-HCT mass
      spectrometer (Bruker Daltonik, Germany) operated in negative ion mode was used
      for detection and quantification of ApnAs. RESULTS: A calibration curve was
      established for diadenosine polyphosphate free plasma in the concentration range
      1.9-125nM (r(2)>0.998) for all analytes. The intra- and inter-day accuracies were
      in the range of 91.4% and 110.9%. The intra- and inter-day precisions were
      determines as 0.1% and 11.4%, respectively. The mean plasma concentrations of
      ApnAs were quantified as 31.9+/-5.9nM for Ap3A, 40.4+/-6.6nM for Ap4A, 10.7+/
      1.5nM for Ap5A and 10.0+/-18.9nM for Ap6A. DISCUSSION: The developed and
      validated ESI MS-based method for quantification of diadenosine polyphosphates in
      human plasma was successfully evaluated within the study. Conclusion Since the
      quantification is based on a volume of 100MUl plasma, this method is highly
      applicable for clinical applications aiming at the validation of the impact of
      highly physiological and pathophysiological active diadenosine polyphosphates.

PMID- 24869946
TI  - Cytotoxicity of cadmium-free quantum dots and their use in cell bioimaging.
AB  - The use of quantum dots (QDots) as bright and photostable probes for long-term
      fluorescence imaging is gaining more interest. Thus far, (pre)clinical use of
      QDots remains limited, which is primarily caused by the potential toxicity of
      QDots. Most QDots consist of Cd2+ ions, which are known to cause high levels of
      toxicity. In order to overcome this problem, several strategies have been tested,
      such as the generation of cadmium-free QDots. In the present study, two types of
      cadmium-free QDots, composed of ZnSe/ZnS (QDotZnSe) and InP/ZnS (QDotInP), were
      studied with respect to their cytotoxicity and cellular uptake in a variety of
      cell types. A multiparametric cytotoxicity approach is used, where the QDots are
      studied with respect to cell viability, oxidative stress, cell morphology, stem
      cell differentiation, and neurite outgrowth. The data reveal slight differences
      in uptake levels for both types of QDots (maximal for QDotZnSe), but clear
      differences in cytotoxicity and cell functionality effects exist, with highest
      toxicity for QDotZnSe. Differences between cell types and between both types of
      QDots can be explained by the intrinsic sensitivity of certain cell types and
      chemical composition of the QDots. At concentrations at which no toxic effects
      can be observed, the functionality of the QDots for fluorescence cell
      visualization is evaluated, revealing that the higher brightness of QDotZnSe
      overcomes most of the toxicity issues compared to that of QDotInP. Comparing the
      results obtained with common Cd2+-containing QDots tested under identical
      conditions, the importance of particle functionality is demonstrated, revealing
      that cadmium-free QDots tested in this study are not significantly better than
      Cd2+-containing QDots for long-term cell imaging and that more work needs to be
      performed in optimizing the brightness and surface chemistry of cadmium-free
      QDots for them to replace currently used Cd2+-containing QDots.

PMID- 24869947
TI  - The synthesis and structure of chiral enamine N-oxides.
AB  - Chiral enamine N-oxides have been synthesised by a diastereoselective
      intermolecular reverse-Cope cycloaddition reaction between chiral hydroxylamines
      and activated acetylenes. Their structures have been investigated by NMR, X-ray
      crystallography and computational methods. 

PMID- 24869948
TI  - Assessment of bioavailable fraction of POPS in surface water bodies in
      Johannesburg City, South Africa, using passive samplers: an initial assessment.
AB  - In this study, the semipermeable membrane device (SPMD) passive samplers were
      used to determine freely dissolved concentrations of polycyclic aromatic
      hydrocarbons (PAHs), polychlorinated biphenyls (PCBs) and organochlorine
      pesticides (OCPs) in selected water bodies situated in and around Johannesburg
      City, South Africa. The devices were deployed for 14 days at each sampling site
      in spring and summer of 2011. Time weighted average (TWA) concentrations of the
      water-borne contaminants were calculated from the amounts of analytes accumulated
      in the passive samplers. In the area of interest, concentrations of analytes in
      water ranged from 33.5 to 126.8 ng l(-1) for PAHs, from 20.9 to 120.9 pg l(-1)
      for PCBs and from 0.2 to 36.9 ng l(-1) for OCPs. Chlorinated pesticides were
      mainly composed of hexachlorocyclohexanes (HCHs) (0.15-36.9 ng l(-1)) and
      dichlorodiphenyltrichloromethane (DDT) with its metabolites (0.03-0.55 ng l(-1)).
      By applying diagnostic ratios of certain PAHs, identification of possible sources
      of the contaminants in the various sampling sites was performed. These ratios
      were generally inclined towards pyrogenic sources of pollution by PAHs in all
      study sites except in the Centurion River (CR), Centurion Lake (CL) and Airport
      River (AUP) that indicated petrogenic origins. This study highlights further need
      to map up the temporal and spatial variations of these POPs using passive
      samplers.

PMID- 24869949
TI  - Management of groundwater in farmed pond area using risk-based regulation.
AB  - Blackfoot disease (BFD) had occurred seriously in the Yichu, Hsuehchia, Putai,
      and Peimen townships of Chia-Nan District of Taiwan in the early days. These four
      townships are the districts of fishpond cultivation domestically in Taiwan.
      Groundwater becomes the main water supply because of short income in surface
      water. The problems of over pumping in groundwater may not only result in land
      subsidence and seawater intrusion but also be harmful to the health of human
      giving rise to the bioaccumulation via food chain in groundwater with arsenic
      (As). This research uses sequential indicator simulation (SIS) to characterize
      the spatial arsenic distribution in groundwater in the four townships. Risk
      assessment is applied to explore the dilution ratio (DR) of groundwater
      utilization, which is defined as the ratio showing the volume of groundwater
      utilization compared to pond water, for fish farming in the range of target
      cancer risk (TR) especially on the magnitude of 10(-4)~10(-6). Our study results
      reveal that the 50th percentile of groundwater DRs served as a regulation
      standard can be used to perform fish farm groundwater management for a TR of 10(
      6). For a TR of 5 * 10(-6), we suggest using the 75th percentile of DR for
      groundwater management. For a TR of 10(-5), we suggest using the 95th percentile
      of the DR standard for performing groundwater management in fish farm areas. For
      the TR of exceeding 5 * 10(-5), we do not suggest establishing groundwater
      management standards under these risk standards. Based on the research results,
      we suggest that establishing a TR at 10(-5) and using the 95th percentile of DR
      are best for groundwater management in fish farm areas.

PMID- 24869951
TI  - Determination of traces of copper and zinc in honeys by the solid phase
      extraction pre-concentration followed by the flame atomic absorption spectrometry
      detection.
AB  - A simple and fast solid phase extraction procedure was developed to pre
      concentrate traces of Cu and Zn prior to their determination in honey samples by
      flame atomic absorption spectrometry. The sample preparation included dissolution
      of honey samples and the passage (at 20 ml/min) of resulting 10% m/v solutions
      (100 ml) through Dowex 50W * 8-400 resin beds in order to quantitatively retain
      Cu and Zn and separate them from the glucose and fructose matrix. Enriched Cu and
      Zn traces were recovered with 5.0 ml of a 3.0 mol/l HCl solution and quantified
      by flame atomic absorption spectrometry. The procedure proposed was used to
      analyze sixty nine commercially available and freshly ripened honey samples
      coming from the Lower Silesia region (Poland). It enabled to measure Cu and Zn
      within the range of 0.01-1.42 and 0.03-15.38 MUg/g, respectively, with precision
      better than 4%. Accuracy, assessed on the basis of the recovery test and the
      comparison of results with those obtained using wet digestion and inductively
      coupled plasma optical emission spectrometry, was ranged from -4% to +6%.
      Detection limits of Cu and Zn achieved with this method were 5 and 7 ng/g,
      respectively.

PMID- 24869950
TI  - Water quality change in dam reservoir and shallow aquifer: analysis on trend,
      seasonal variability and data reduction.
AB  - Change of water quality in dam reservoir and aquifer complicates safe drinking
      water supply. Few parameters are monitored to control water quality in these
      sources. Adequate knowledge on the correlation structure, interaction effect,
      trends and seasonal variability of these parameters is essential to control water
      quality. This study applied time series and multivariate analyses on 15 water
      quality parameters, collected from the King Fahd dam reservoir (L1) and aquifer
      (L2) in Saudi Arabia during April 2010 to February 2012. Moderate to strong
      correlations were observed between sulfate, hardness, fluoride, chloride,
      magnesium, conductivity, turbidity and total dissolved solids (TDS), while
      separate clusters were visible for TDS-chloride-magnesium-conductivity; fluoride
      turbidity; chloride-hardness; ammonia-nitrate; and calcium-magnesium-hardness.
      Four major principal components explained 81.1% and 83.2% of the overall
      variances in L1 and L2, respectively. The factor analysis showed that 53% and 67%
      of the data were necessary to explain 81.3% and 83.2% of total variances for L1
      and L2, respectively, indicating the possibility of data reduction. Possible
      degradation of water quality in these sources was highlighted, while such
      degradation may require enhanced treatment for producing drinking water in
      future.

PMID- 24869953
TI  - Multisource emission retrieval within a biogas plant based on inverse dispersion
      calculations--a real-life example.
AB  - Open digestate storage tanks were identified as one of the main methane (CH4)
      emitters of a biogas plant. The main purpose of this paper is to determine these
      emission rates using an inverse dispersion technique in conjunction with open
      path tunable diode laser spectroscopy (OP-TDLS) concentration measurements for
      multisource reconstruction. Since the condition number, a measure of "ill
      conditioned" matrices, strongly influences the accuracy of source reconstruction,
      it is used as a diagnostic of error sensitivity. The investigations demonstrate
      that the condition number for a given source-sensor configuration in the highly
      disturbed flow field within the plant significantly depends on the meteorological
      conditions (e.g., wind speed, stratification, wind direction, etc.). The CH4
      emissions are retrieved by removing unrepresentative periods with high condition
      numbers, which indicate uncertainty in recovering the individual sources. In a
      final step, the CH4 emissions are compared with the maximum biological methane
      potential (BMP) in the digestate analyzed under laboratory conditions. The
      retrieved methane emission rates represent an average of 50% of the maximum BMP
      of the stored digestate in the winter months, while they comprised an average of
      85% during the measurement campaigns in the summer months. The results indicate
      that the open tanks have the potential to represent a substantial emission source
      even during colder periods.

PMID- 24869952
TI  - Seasonal dynamics of Vibrio cholerae and its phages in riverine ecosystem of
      Gangetic West Bengal: cholera paradigm.
AB  - The Gangetic delta is a century-old cholera endemic belt where the role of
      riverine-estuarine ecosystem in cholera transmission has never been elucidated.
      Seasonality, distribution, and abundance of environmental Vibrio cholerae O1/O139
      and vibriophage in Hooghly riverine-estuarine environment and their correlation
      with cholera incidence pattern in West Bengal, India, have been analyzed for the
      first time across summer, monsoon, and winter months. A total of 146 water
      samples collected from two sites of the Hooghly River (Howrah and Diamond
      Harbour) were analyzed physicochemically along with cultivable Vibrio count
      (CVC), V. cholerae O1/O139, and vibriophages. V. cholerae O1 was detected in 56
      (38.3%) samples, while 66 (45.2%) were positive for V. cholerae O1 phages. Flood
      tide, water temperature (31 +/- 1.6  degrees C), and turbidity (>=250
      nephelometric turbidity unit (NTU)) significantly stimulated V. cholerae and
      vibriophage abundance in riverine ecosystem. Solitary existence of V. cholerae O1
      and phages (p < 0.0001) in aquatic environment divulges the dominance of either
      of the entity (V. cholerae O1 or V. cholerae O1 Phi) on the other. Significant
      association (p < 0.05) between Kolkata cholera cases and V. cholerae O1 in
      aquatic environment implies the role of riverine-estuarine ecosystem in cholera
      transmission. A "biomonitoring tool" of physicochemical stimulants, tidal, and
      climatic variants has been proposed collating V. cholerae and phage dynamics that
      can forewarn any impending cholera outbreak.

PMID- 24869954
TI  - Effect of repeated applications of buprofezin and acephate on soil cellulases,
      amylase, and invertase.
AB  - The impact of repeated applications of buprofezin and acephate, at concentrations
      ranging from 0.25 to 1.0 kg ha(-1), on activities of cellulases, amylase, and
      invertase in unamended and nitrogen, phosphorous, and potassium (NPK) fertilizer
      amended soil planted with cotton was studied. The nontarget effect of selected
      insecticides, when applied once, twice, or thrice on soil enzyme activities, was
      dose-dependent; the activities decreased with increasing concentrations of
      insecticides. However, there was a rapid decline in activities of enzymes after
      three repeated applications of insecticides in unamended or NPK-amended soil. Our
      data clearly suggest that insecticides must be applied judiciously in pest
      management in order to protect the enzymes largely implicated in soil fertility.

PMID- 24869955
TI  - Monitoring of pesticide residues levels in fresh vegetable form Heibei Province,
      North China.
AB  - In this study, 226 samples of seven types of domestic vegetables collected from
      several vegetable-growing regions in Hebei Province of China were tested for the
      presence of 38 different agricultural pesticides using a gas chromatograph
      equipped with electron capture and nitrogen phosphorus detectors. The aim of this
      study was to investigate the distribution of pesticides in main vegetables from
      Hebei Province. Results showed that, in 65.93% of the samples, no residues were
      found, 31.42% of the samples contained pesticide residues at or below the maximum
      residue levels (MRLs), and 2.65% of the samples contained pesticide residues
      above MRL. The most frequently detected pesticides were acephate (31), followed
      by cyhalothrin (15), bifenthrin (8), omethoate (6), isazophos (6), dimethoate
      (5), chlorpyrifos (2), and malathion (1). Some (1.33%) of the samples contained
      multiple residues. The results provide useful information on the current
      contamination status of a key agricultural area in North China, and points to the
      continuous monitoring and strict regulation of pesticide use on vegetables are
      necessary.

PMID- 24869956
TI  - Extraction of the metagenomic DNA and assessment of the bacterial diversity from
      the petroleum-polluted sites.
AB  - The assessment of the microbial diversity of the entire community of a given
      habitat requires the extraction of the total environmental DNA. Metagenomic
      investigations of a petroleum-polluted habitat have its unique challenges. The
      specific methods were developed for the extraction of high-quality metagenome in
      good quantity from the petroleum-polluted saline and non-saline sites in Gujarat
      (India). The soil samples were washed to remove the toxic, hazardous organic
      pollutants which might interfere with the recovery of the metagenomic DNA. The
      metagenomic DNA extraction results were encouraging with the mechanical bead
      beating, soft lysis, and combination of both. The extracted DNA was assessed for
      its purity and yield followed by its application in the amplification of the 16S
      rRNA region. The amplicons were used for judging the molecular diversity by the
      denaturing gradient gel electrophoresis (DGGE). The microbial diversity was also
      analyzed statistically by calculating various diversity indices and principal
      component analysis (PCA). The results on the metagenomic diversity of the
      bacterial population among the three cohorts based on the culture-independent
      technique exhibited significant difference among the PAH sites and Okha-Madhi and
      Porbandar Madhavpur habitats. 

PMID- 24869957
TI  - Influenza A virus and TLR7 activation potentiate NOX2 oxidase-dependent ROS
      production in macrophages.
AB  - Influenza A virus infects resident alveolar macrophages in the respiratory tract
      resulting in Toll like receptor 7 (TLR7) activation that triggers an inflammatory
      response to resolve the infection. Macrophages are also major sources of reactive
      oxygen species (ROS) via the NOX2-containing NADPH oxidase. Although ROS are
      crucial for pathogen clearance, in response to influenza A virus, ROS are touted
      as being culprit mediators of the lung tissue injury. The aim of the present
      study was to determine whether influenza A virus infection and TLR7 activation of
      macrophages, results in alterations in their ROS production. Here we demonstrate
      using immunofluorescence that influenza A virus (Hong Kong X-31 strain; H3N2)
      internalizes in RAW264.7 cells and mouse alveolar macrophages within 1 h,
      resulting in a significant enhancement in the stimulated NOX2 oxidase-dependent
      oxidative burst, although virus had no effect on basal ROS. The specific TLR7
      agonist imiquimod (10 MUg/ml) elevated basal superoxide production and, in a
      similar fashion to influenza A virus, enhanced NOX2 oxidase-dependent oxidative
      burst. By contrast, the TLR3 agonist, poly I:C (1-100 MUg/ml) failed to influence
      the oxidative burst to NOX2 oxidase. A peptide corresponding to the region 337
      348 on p47phox conjugated to a HIV-tat, designed to inhibit the phosphorylation
      of Ser346 on p47phox suppressed the influenza A virus- and imiquimod-induced
      enhancement in the oxidative burst. In conclusion, this study demonstrates for
      the first time that influenza A virus and TLR7 activation enhance the NOX2
      oxidase-dependent oxidative burst in macrophages, which might underpin the acute
      lung injury to influenza A virus infection.

PMID- 24869959
TI  - Intrinsic and extrinsic risk factors for sagging eyelids.
AB  - IMPORTANCE: Sagging eyelids, or dermatochalasis, are a frequent concern in older
      adults. It is considered a feature of skin aging, but risk factors other than
      aging are largely unknown. OBJECTIVE: To study nongenetic and genetic risk
      factors for sagging eyelids. DESIGN: Upper eyelid sagging was graded in 4
      categories of severity using digital photographs. Dermatochalasis was defined as
      the eyelid hanging over the eyelashes. Age, sex, skin color, tanning ability,
      hormonal status in women, current smoking, body mass index, and sun protection
      behavior were analyzed in a multivariable multinomial logistic regression model.
      Genetic predisposition was assessed using heritability analysis and a genome-wide
      association study. SETTING AND PARTICIPANTS: The study was performed in 2
      independent population-based cohorts. The Rotterdam Study included older adults
      from one district in Rotterdam, the Netherlands, and the UK Adult Twin Registry
      (TwinsUK) included twins from all over the United Kingdom. Participants were 5578
      unrelated Dutch Europeans (mean age, 67.1 years; 44.0% male) from the Rotterdam
      Study and 2186 twins (mean age, 53.1 years; 10.4% male) from the TwinsUK. MAIN
      OUTCOMES AND MEASURES: Sagging eyelid severity levels, ranging from 1 (normal
      control) to 4 (severe sagging). RESULTS: Among 5578 individuals from the
      Rotterdam Study, 17.8% showed dermatochalasis (moderate and severe sagging
      eyelids). Significant and independent risk factors for sagging eyelids included
      age, male sex, lighter skin color, and higher body mass index. In addition,
      current smoking was borderline significantly associated. Heritability of sagging
      eyelids was estimated to be 61% among 1052 twin pairs from the TwinsUK (15.6%
      showed dermatochalasis). A meta-analysis of genome-wide association study results
      from 5578 Rotterdam Study and 1053 TwinsUK participants showed a genome-wide
      significant recessive protective effect of the C allele of rs11876749 (P = 1.7 *
      10(-8)). This variant is located close to TGIF1 (an inducer of transforming
      growth factor beta), which is a known gene associated with skin aging.
      CONCLUSIONS AND RELEVANCE: This is the first observational study to date
      demonstrating that other risk factors (male sex, genetic variants, lighter skin
      color, high body mass index, and possibly current smoking) in addition to aging
      are involved in the origin of sagging eyelids.

PMID- 24869958
TI  - Advances in mesenchymal stem cell-based strategies for cartilage repair and
      regeneration.
AB  - Significant research efforts have been undertaken in the last decade in the
      development of stem cell-based therapies for cartilage repair. Among the various
      stem cell sources, mesenchymal stem cells (MSCs) demonstrate great promise and
      clinical efficacy in cartilage regeneration. With a deeper understanding of stem
      cell biology, new therapeutics and new bioengineering approaches have emerged and
      showed potential for further developments. Of note, there has been a paradigm
      shift in applying MSCs for tissue regeneration from the use of stem cells for
      transplantation to the use of stem cell-derived matrix and secretome components
      as therapeutic tools and agents for cartilage regeneration. In this review, we
      will discuss the emerging role of MSCs in cartilage regeneration and the most
      recent advances in development of stem cell-based therapeutics for cartilage
      regeneration. 

PMID- 24869962
TI  - The types of Anthomyiidae (Diptera) in the Shanghai Entomological Museum, Chinese
      Academy of Science, China.
AB  - An annotated list of the type-specimens of Anthomyiidae deposited in the Shanghai
      Entomological Museum, China, is presented. A total of 196 holotypes and 479
      paratypes representing 212 nominal species (207 valid, 5 synonyms) were
      recognized and are listed alphabetically. Bibliographical data of the original
      description, labels and condition of the type-specimens and the current name of
      the species are provided. At the end, a nomenclatural summary and a geographic
      summary are provided. 

PMID- 24869960
TI  - Swimming with predators and pesticides: how environmental stressors affect the
      thermal physiology of tadpoles.
AB  - To forecast biological responses to changing environments, we need to understand
      how a species's physiology varies through space and time and assess how changes
      in physiological function due to environmental changes may interact with
      phenotypic changes caused by other types of environmental variation. Amphibian
      larvae are well known for expressing environmentally induced phenotypes, but
      relatively little is known about how these responses might interact with changing
      temperatures and their thermal physiology. To address this question, we studied
      the thermal physiology of grey treefrog tadpoles (Hyla versicolor) by determining
      whether exposures to predator cues and an herbicide (Roundup) can alter their
      critical maximum temperature (CTmax) and their swimming speed across a range of
      temperatures, which provides estimates of optimal temperature (Topt) for swimming
      speed and the shape of the thermal performance curve (TPC). We discovered that
      predator cues induced a 0.4 degrees C higher CTmax value, whereas the herbicide
      had no effect. Tadpoles exposed to predator cues or the herbicide swam faster
      than control tadpoles and the increase in burst speed was higher near Topt. In
      regard to the shape of the TPC, exposure to predator cues increased Topt by 1.5
      degrees C, while exposure to the herbicide marginally lowered Topt by 0.4 degrees
      C. Combining predator cues and the herbicide produced an intermediate Topt that
      was 0.5 degrees C higher than the control. To our knowledge this is the first
      study to demonstrate a predator altering the thermal physiology of amphibian
      larvae (prey) by increasing CTmax, increasing the optimum temperature, and
      producing changes in the thermal performance curves. Furthermore, these plastic
      responses of CTmax and TPC to different inducing environments should be
      considered when forecasting biological responses to global warming. 

PMID- 24869961
TI  - Characterization of aging-associated cardiac diastolic dysfunction.
AB  - AIMS: Diastolic dysfunction is common in geriatric heart failure. A reliable
      parameter to predict myocardium stiffness and relaxation under similar end
      diastolic pressure is being developed. We propose a material and mathematical
      model for calculating myocardium stiffness based on the concept of linear
      correlation between [Formula: see text] and wedge pressure. METHODS AND RESULTS:
      We enrolled 919 patients (male: [Formula: see text][Formula: see text]). Compared
      with the younger population of controls (mean age: [Formula: see text] years;
      [Formula: see text]; male: [Formula: see text] [Formula: see text]), the elderly
      (mean age: [Formula: see text]; [Formula: see text]; male: [Formula: see text]
      [Formula: see text]) had a greater prevalence of hypertension, diabetes mellitus,
      and coronary artery disease (all [Formula: see text]). We collected their M-mode
      and 2-D echocardiographic volumetric parameters, intraventricular filling
      pressure, and speckle tracking images to establish a mathematical model. The
      feasibility of this model was validated. The average early diastolic velocity of
      the mitral annulus assessed using tissue Doppler imaging was significantly
      attenuated in the elderly ([Formula: see text]: [Formula: see text] vs. [Formula:
      see text]; [Formula: see text]) and corresponded to the higher estimated wedge
      ([Formula: see text]) pressure ([Formula: see text] vs. [Formula: see text];
      [Formula: see text]) in that cohort. E (Young's modulus) was calculated to
      describe the tensile elasticity of the myocardium. With the same intraventricular
      filling pressure, E was significantly higher in the elderly, especially those
      with [Formula: see text] values [Formula: see text]. Compared with diastolic
      dysfunction parameters, E also presented sentinel characteristics more sensitive
      for detecting early myocardial relaxation impairment, which indicates stiffer
      myocardium in aging hearts. CONCLUSION: Our material and geometric mathematical
      model successfully described the stiffer myocardium in aging hearts with higher
      intraventricular pressure. Additional studies that compare individual
      differences, especially in health status, are needed to validate its application
      for detecting diastolic heart failure.

PMID- 24869963
TI  - On two reports associated with James Wood-Mason and Alfred William Alcock
      published by the Indian Museum and the Indian Marine Survey between 1890 and
      1891: implications for malacostracan nomenclature.
AB  - Two rare documents associated with the Indian Museum and the Indian Marine Survey
      for the administrative year April 1890 to March 1891 have been examined and found
      to have nomenclatural consequences for malacostracan crustaceans. Even though
      they constitute available published works according to the International Code for
      Zoological Nomenclature, these reports have rarely been cited. Dating these two
      publications is of importance as they make decapod scientific names available
      and, in a few instances, describe the same taxa. After searching the collections
      deposited in the Asian and African Room, British Library, the Administration
      Report of the Indian Marine for the year April 1890 to March 1891 could be dated
      with some degree of certainty as 25 August 1891. In contrast, dating the Indian
      Museum Annual Report proved more difficult because after examination of copies
      held by the General Library in the Natural History Museum, London, it was evident
      that not all of these reports were consistently published on time to meet an end
      of year deadline. However, the publication of volume XXII of the Indian Museum
      Annual Report for the year April 1890 to March 1891 appeared to be contemporary
      with the year printed at the bottom of the title page. As no exact date could be
      established with confidence, the publication date for this volume was fixed as 31
      December 1891 in accordance with ICZN Art. 21.3.2. Therefore the Administration
      Report of the Indian Marine (published 25 August 1891) is considered to take
      precedence over the Indian Museum Annual Report (published 31 December 1891) and
      as such the names made available in the former take priority. As original copies
      of the Administration Report of the Indian Marine are not readily available in
      most libraries and few scientists have actually had access to these publications,
      the relevant Appendix No. XIII, in which the names of several malacostracan taxa
      are made available, is reproduced here. Since the appendix is not conclusively
      attributable to a specific author, it is considered to be written anonymously and
      should therefore be cited as Anonymous (1891). A number of names in Appendix No.
      XIII are available since they are accompanied by a brief description of the taxa
      they denote, and are either attributable to James Wood-Mason or remain with
      anonymous authorship; others are nomina nuda without a diagnosis or indication,
      or have been diagnosed previously in the "Natural History Notes from H.M. Indian
      Marine Survey Steamer Investigator". The nomenclatural implications for eight
      names made available in Anonymous (1891) are discussed: Glyphocrangon caeca,
      Glyphocrangon sculptus var. coecescens, Psalidopodidae, Psalidopus, Psalidopus
      mirabilis, Psathyrocaris, Psathyrocaris fragilis and Psopheticus crepitans. The
      nomenclatural history of various other taxa, initially denoted by unavailable
      names in Anonymous (1891), is also documented. The authorships of the various
      crustacean taxa collected by the Indian Marine Survey Steamer Investigator during
      the seasons 1889-1890 and 1890-1891, and published in two series of connected
      parts in the Annals and Magazine of Natural History, are also re-assessed and
      summarised. A rare document containing the list of R.I.M.S. Investigator stations
      for the period 1884-1913 is reproduced for the future benefit of the scientific
      community.  

PMID- 24869964
TI  - A revision of the water beetle genus Hydraena Kugelann for southern Africa
      (Coleoptera: Hydraenidae).
AB  - The southern African species of the water beetle genus Hydraena Kugelann, 1794,
      are revised. Twenty-eight new species are described, and redescriptions and new
      collection records are given for three previously described species, based on the
      examination and databasing of 11,534 specimens from 488 localities/events. Male
      genitalia are illustrated, and high resolution habitus images of the holotypes
      are provided. Distribution maps are given for the 31 species of Hydraena now
      known from southern Africa, including Namibia, South Africa, Lesotho, Botswana,
      Zimbabwe, and the extreme southern part of Angola. New species of Hydraena are:
      H. armatura (Zimbabwe: Tributary stream of the Mutoragundu River); H. biseptosa
      (South Africa: Mpumalanga Province, Soutpansberg, Entabeni); H. capensis (South
      Africa: Eastern Cape Province, Chapman's Bay); H. caprivica (Namibia: East
      Caprivi: Katima Mulilo); H. clavicula (South Africa: Mpumalanga Province,
      Uitsuk); H. cooperoides (Namibia: Naukluft River); H. duodecimata (South Africa:
      Northern Cape Province, Richtersveld, Oemsberg); H. elephanta (Angola: Altoplano,
      Ongueria); H. favulosa (Zimbabwe: Matapos National Park); H. genumorpha (South
      Africa: KwaZulu-Natal Province, Karkloof Grassveld); H. habitiva (South Africa:
      Mpumalanga Province, Nelshoogte); H. humanica (South Africa: Mpumalanga Province,
      Blyderiver Canyon); H. injectiva (South Africa: Mpumalanga Province, Nelshoogte);
      H. mpumalanga (South Africa: Mpumalanga Province, Soutpansberg, Entabeni); H.
      multimurata (South Africa: Mpumalanga Province, Kruger Nat. Pk., Letaba River);
      H. namibiensis (Namibia: C. Namib desert, Numis Wasser); H. natiforma (South
      Africa: Free State Province, Kruger Nat'l Park, Pretariuskop); H. neoaccurata
      (South Africa: Mpumalanga Province, Nelshoogte); H. nomenipes (South Africa:
      Eastern Cape Province, S. coast, Dwesa forest reserve); H. pisciforma (South
      Africa: Mpumalanga Province, Kruger National Park, Skukuza, Sabie River); H.
      profunda (South Africa: Mpumalanga Province, God's Window); H. reflectiva (South
      Africa: Eastern Cape Province, S. coast, Dwesa forest reserve); H. sebastiani
      (South Africa: Western Cape Province, Groot Toren farm); H. tiara (South Africa:
      Mpumalanga Province, Vaal River where crossed by Ermelo-Lake Chrissie Road); H.
      uniforma (Namibia: Brandberg, Wasserfallflache); H. vadosa (South Africa: Eastern
      Cape Province, Amatole, Pirie Forest); H. zimbabwensis (Zimbabwe: Matapos
      National Park). 

PMID- 24869965
TI  - Abelisauridae (Dinosauria: Theropoda) from the Late Jurassic of Portugal and
      dentition-based phylogeny as a contribution for the identification of isolated
      theropod teeth.
AB  - Theropod dinosaurs form a highly diversified clade, and their teeth are some of
      the most common components of the Mesozoic dinosaur fossil record. This is the
      case in the Lourinha Formation (Late Jurassic, Kimmeridgian-Tithonian) of
      Portugal, where theropod teeth are particularly abundant and diverse. Four
      isolated theropod teeth are here described and identified based on morphometric
      and anatomical data. They are included in a cladistic analysis performed on a
      data matrix of 141 dentition-based characters coded in 60 taxa, as well as a
      supermatrix combining our dataset with six recent datamatrices based on the whole
      theropod skeleton. The consensus tree resulting from the dentition-based data
      matrix reveals that theropod teeth provide reliable data for identification at
      approximately family level. Therefore, phylogenetic methods will help identifying
      theropod teeth with more confidence in the future. Although dental characters do
      not reliably indicate relationships among higher clades of theropods, they
      demonstrate interesting patterns of homoplasy suggesting dietary convergence in
      (1) alvarezsauroids, therizinosaurs and troodontids; (2) coelophysoids and
      spinosaurids; (3) compsognathids and dromaeosaurids; and (4) ceratosaurids,
      allosauroids and megalosaurids. Based on morphometric and cladistic analyses, the
      biggest tooth from Lourinha is referred to a mesial crown of the megalosaurid
      Torvosaurus tanneri, due to the elliptical cross section of the crown base, the
      large size and elongation of the crown, medially positioned mesial and distal
      carinae, and the coarse denticles. The smallest tooth is identified as
      Richardoestesia, and as a close relative of R. gilmorei based on the weak
      constriction between crown and root, the "eight-shaped" outline of the base crown
      and, on the distal carina, the average of ten symmetrically rounded denticles per
      mm, as well as a subequal number of denticles basally and at mid-crown. Finally,
      the two medium-sized teeth belong to the same taxon and exhibit pronounced
      interdenticular sulci between distal denticles, hooked distal denticles for one
      of them, an irregular enamel texture, and a straight distal margin, a combination
      of features only observed in abelisaurids. They provide the first record of
      Abelisauridae in the Jurassic of Laurasia and one of the oldest records of this
      clade in the world, suggesting a possible radiation of Abelisauridae in Europe
      well before the Upper Cretaceous. 

PMID- 24869966
TI  - Circulating levels of soluble MICB in infants with symptomatic primary dengue
      virus infections.
AB  - Dengue is the most prevalent arthropod-borne viral illness in humans. A MHC class
      I polypeptide-related sequence B (MICB) single nucleotide polymorphism (SNP) was
      previously associated with symptomatic dengue compared to non-dengue causes of
      acute febrile illnesses in infants. We measured circulating levels of soluble
      (s)MICB in the sera of infants with symptomatic primary dengue virus infections.
      We found that serum levels of sMICB increased between pre-infection and acute
      illness among infants with symptomatic primary dengue virus infections. The
      likelihood of being hospitalized with an acute primary DENV infection during
      infancy also tended to be higher with increasing acute illness sMICB levels. The
      elevation of sMICB during acute primary DENV infections in infants likely
      represents an immune evasion strategy and contributes to the severity of the
      acute illness. 

PMID- 24869967
TI  - Traumatic testicular dislocation.
AB  - INTRODUCTION: Traumatic testicular dislocation is a rare entity. It occurs after
      a direct blunt scrotal trauma causing the testicle to migrate outside the
      scrotum, most frequently to the superficial inguinal region. MATERIALS AND
      METHODS: A review of the diagnostic database of our two institutions was
      performed searching for complex genital trauma between 1990 and 2012. RESULTS:
      Seven cases of traumatic testicular dislocation were identified (four on the left
      side; one on the right side and two bilateral) for a total of nine testicles. Six
      were motorcycle accidents, and the other case suffered a pelvic crush injury. All
      victims had significant associated injuries, one case had an open dislocation and
      two were killed by the accident. The testicle was located at the inguinal region
      in four cases at the suprapubic area in four, and the other was an open
      dislocation. Diagnosis was suspected with the physical examination and confirmed
      by Doppler ultrasound; however, in one case, the diagnosis was missed during
      several weeks. In one case, the testicle was reduced into the scrotum immediately
      at the emergency department. Two cases were operated shortly after admission,
      performing testicular reduction into the scrotum and standard orchidopexy. Two
      other cases underwent delayed intervention, and both needed release of peri
      testicular adhesions. Two cases (both bilateral) died at the accident site and
      were diagnosed by autopsy. In all surviving cases, it was possible to obtain a
      satisfactory orchidopexy with gonadal preservation. CONCLUSIONS: Traumatic
      testicular dislocation is rare and diagnosis can be elusive. It should be
      suspected in motorcycle and high-energy accidents around the groin area and
      depends on a careful physical examination. With proper management, prognosis is
      excellent.

PMID- 24869968
TI  - Morning blood pressure surge is associated with death in hypertensive patients.
AB  - BACKGROUND: Morning blood pressure surge (MS), defined as the difference between
      the mean blood pressure (BP) 2 h after waking up and the mean of the three lowest
      BP values during sleep, has been correlated with increased cardiovascular risk.
      We sought to evaluate its association with cardiovascular events and death.
      METHODS: We retrospectively analyzed data from 632 hypertensive patients [median
      age 58 years (50-67 years), 37% men] who underwent ambulatory BP monitoring
      between January 2005 and December 2006. Patients were divided into two groups
      according to MS (>=41 mmHg and <41 mmHg), and mortality from any cause was
      retrieved after a median time of 50 months (46-54 months). RESULTS: Patients with
      MS of 41 mmHg or higher were older, had a higher daytime systolic BP, as well as
      a higher systolic and diastolic dipping, and a lower night-time diastolic BP.
      During follow-up, there were 19 deaths and MS of 41 mmHg or higher was associated
      with a higher hazard for death in the crude model [hazard ratio: 3.47 (95%
      confidence interval: 1.25-9.65)], as well as after adjustments for age and the
      presence of diabetes [hazard ratio: 3.35 (95% confidence interval: 1.18-9.49)].
      CONCLUSION: An increased BP surge is associated with higher hazard for death.
      Future studies specifically designed to evaluate the real impact of MS on
      outcomes, as well as to define its optimal cutoff value, are required.

PMID- 24869969
TI  - Cancer cachexia and diabetes: similarities in metabolic alterations and possible
      treatment.
AB  - Cancer cachexia is a metabolic syndrome featuring many alterations typical of
      type 2 diabetes (T2D). While muscle wasting is a hallmark of cachexia,
      epidemiological evidence also supports an accelerated age-related muscle loss in
      T2D. Insulin resistance manifests in both conditions and impairs glucose disposal
      and protein anabolism by tissues. A greater contribution of gluconeogenesis to
      glucose production may limit amino acid availability for muscle protein
      synthesis, further aggravating muscle loss. In the context of inter-dependence
      between glucose and protein metabolism, the present review summarizes the current
      state of knowledge on alterations that may lead to muscle wasting in human
      cancer. By highlighting the similarities with T2D, a disease that has been more
      extensively studied, the objective of this review is to provide a better
      understanding of the pathophysiology of cancer cachexia and to consider potential
      treatments usually targeted for T2D. Nutritional approaches aimed at stimulating
      protein anabolism might include specially formulated food with optimal protein
      and amino acid composition. Because the gradual muscle loss in T2D may be
      attenuated by diabetes treatment, anti-diabetic drugs might be considered in
      cachexia treatment. Metformin emerges as a choice candidate as it acts both on
      reducing gluconeogenesis and improving insulin sensitivity, and has demonstrated
      tumour suppressor properties in multiple cancer types. Such a multimodal approach
      to slow or reverse muscle wasting in cachexia warrants further investigation. 

PMID- 24869970
TI  - Role of n-3 fatty acids in muscle loss and myosteatosis.
AB  - Image-based methods such as computed tomography for assessing body composition
      enables quantification of muscle mass and muscle density and reveals that low
      muscle mass and myosteatosis (fat infiltration into muscle) are common in people
      with cancer. Myosteatosis and low muscle mass have emerged as independent risk
      factors for mortality in cancer; however, the characteristics and pathogenesis of
      these features have not been resolved. Muscle depletion is associated with low
      plasma eicosapentaenoic (20:5n-3) and docosahexaenoic (22:6n-3) in cancer and
      supplementation with n-3 fatty acids has been shown to ameliorate muscle loss and
      myosteatosis in clinical studies, suggesting a relationship between n-3 fatty
      acids and muscle health. Since the mechanisms by which n-3 fatty acids alter body
      composition in cancer remain unknown, related literature from other conditions
      associated with myosteatosis, such as insulin resistance and obesity is
      considered. In these noncancer conditions, it has been reported that n-3 fatty
      acids act by increasing insulin sensitivity, reducing inflammatory mediators, and
      altering adipokine profiles and transcription factors; therefore, the
      plausibility of these mechanisms of action in the neoplastic state are
      considered. The aim of this review is to summarize what is known about the
      effects of n-3 fatty acids with regards to muscle condition and to discuss
      potential mechanisms for effects of n-3 fatty acids on muscle health. 

PMID- 24869971
TI  - Flaxseed and its lignan and oil components: can they play a role in reducing the
      risk of and improving the treatment of breast cancer?
AB  - Flaxseed (FS), rich in the phytoestrogen lignans and alpha-linolenic acid-rich
      oil, has been suggested to have an anticancer effect. Questions remain whether FS
      and its lignan and oil components are effective in reducing breast cancer risk
      and tumour growth, and can interact beneficially with breast cancer drugs. To
      find answers, in vitro, animal, observational, and clinical studies on FS and its
      lignan and oil components were reviewed. The majority of studies in various
      rodent models show that 2.5%-10% FS diet or the equivalent amount of lignan or
      oil reduces tumour growth. Ten percent FS and equivalent lignans do not interfere
      with but rather increase the effectiveness of tamoxifen (80 mg/day) while the 4%
      FS oil increases trastuzumab/Herceptin (2.5 mg/kg) effectiveness. Observational
      studies show that FS and lignan intake, urinary excretion, or serum levels are
      associated with reduced risk, particularly in postmenopausal women. Lignans
      reduce breast cancer and all-cause mortality by 33%-70% and 40%-53%,
      respectively, without reducing tamoxifen effectiveness. Clinical trials show that
      FS (25 g/day with 50 mg lignans; 32 days) reduces tumour growth in breast cancer
      patients and lignans (50 mg/day; 1 year) reduces risk in premenopausal women.
      Mechanisms include decreased cell proliferation and angiogenesis and increased
      apoptosis through modulation of estrogen metabolism and estrogen receptor and
      growth factor receptor signalling pathways. More clinical trials are needed but
      current overall evidence indicates that FS and its components are effective in
      the risk reduction and treatment of breast cancer and safe for consumption by
      breast cancer patients. 

PMID- 24869972
TI  - Association of total adiposity and computed tomographic measures of regional
      adiposity with incident cancer risk: a prospective population-based study of
      older adults.
AB  - Obesity is associated with increased risk of many types of cancer. Less is known
      regarding associations between adipose depots and cancer risk. We aimed to
      explore relationships between adipose depots, risk of cancer, and obesity-related
      cancer (per NCI definition) in participants initially aged 70-79 years without
      prevalent cancer (1179 men, 1340 women), and followed for incident cancer for 13
      years. Measures included body mass index (BMI), total adipose tissue from dual
      energy X-ray absorptiometry, and computed tomography measures of visceral adipose
      tissue (VAT), abdominal subcutaneous adipose tissue, thigh intermuscular adipose
      tissue, and thigh muscle attenuation (Hounsfield unit, HU), where low HU
      indicates fatty infiltration. Hazard ratios (HR) and 95% confidence intervals
      (CIs) were estimated by Cox proportional hazards models adjusted for
      demographics, lifestyle variables, and medical conditions. During follow-up, 617
      participants developed cancer of which 224 were obesity-related cancers. Total
      adipose tissue and VAT were positively associated with cancer risk among women
      (HR 1.14, 95% CI 1.01-1.30 per SD increase; HR 1.15, 95% CI 1.02-1.30 per SD
      increase). There were no associations with cancer risk among men. Total adipose
      tissue was positively associated with obesity-related cancer risk among women (HR
      1.23, 95% CI 1.03-1.46 per SD increase). VAT was positively associated with
      obesity-related cancer risk among men (HR 1.30, 95% CI 1.06-1.60 per SD increase)
      and remained associated even with adjustment for BMI (HR 1.40, 95% CI 1.08-1.82
      per SD increase). These findings provide insight into relationships between
      specific adipose depots and cancer risk and suggest differential relationships
      among men and women. 

PMID- 24869973
TI  - The association between body composition and toxicities from the combination of
      Doxil and trabectedin in patients with advanced relapsed ovarian cancer.
AB  - Emerging research suggests that body composition can predict toxicity of certain
      chemotherapeutic agents. We used data from a clinical study to investigate
      associations between body composition and combined DOXIL (pegylated liposomal
      doxorubicin; PLD) and trabectedin (Yondelis) treatment, an effective treatment
      for ovarian cancer that shows high interpatient variation in toxicity profile.
      Patients (n = 74) participating in a phase III randomized trial of relapsed
      advanced ovarian cancer receiving PLD (30 mg/m(2)) and trabectedin (1.1 mg/m(2))
      were included. Muscle tissue was measured by analysis of computerized tomography
      images, and an extrapolation of muscle and adipose tissue to lean body mass (LBM)
      and fat mass (FM) were employed. Toxicity profile after cycle 1 was used and
      graded according to the National Cancer Institute Common Toxicity Criteria
      (version 3). Patients presented with a wide range of body composition. In
      overweight and obese patients (body mass index (BMI) >= 25 kg/m(2), n = 48)
      toxicity was more prevalent in those with lower BMI (p = 0.028) and a lower FM (n
      = 43, p = 0.034). Although LBM alone was not predictive of toxicity, a lower
      FM/LBM ratio was the most powerful variable associated with toxicity (p = 0.006).
      A different pattern emerged among normal weight patients (n = 26) where toxicity
      was rare among patients with smaller BMI (<21 kg/m(2)). A clear association
      between both FM and LBM (primarily driven by FM) in explaining PLD plus
      trabectedin toxicity emerged, but only in individuals with excess body weight,
      with a lower ratio predicting higher exposure and risk for toxicity. 

PMID- 24869974
TI  - Dietary changes and food intake in the first year after breast cancer treatment.
AB  - Understanding dietary habits of women after breast cancer is a critical first
      step in developing nutrition guidelines that will support weight management and
      optimal health in survivorship; however, limited data are available. The
      objective of this study was to describe changes in diet among breast cancer
      survivors in the first year after treatment, and to evaluate these changes in the
      context of current dietary intake. Changes in diet were assessed in 28 early
      stage breast cancer survivors, using a self-reported survey in which women
      identified changes in food intake since their diagnosis. Current dietary intake
      was estimated from 3-day food records and described relative to current
      recommendations. The majority of women reported changes in diet after diagnosis,
      most common being an increase in vegetables/fruit and fish, lower intake of red
      meat, and reduced alcohol. Many women reported that these changes were initiated
      during active treatment. Dietary changes were largely consistent with current
      recommendations for cancer prevention; however, some women were still above the
      guidelines for total and saturated fat, and many were below recommendations for
      vegetables/fruit, milk/alternatives, calcium, and vitamin D. Evidence that some
      women are willing and able to initiate positive changes in diet early in the
      treatment trajectory suggests that early intervention may be effective in
      promoting dietary habits that will assist with weight management and overall
      health. Data on current dietary intake highlights several possible targets for
      dietary intervention in this population. 

PMID- 24869975
TI  - Feasibility and efficacy of a 12-week supervised exercise intervention for
      colorectal cancer survivors.
AB  - Exercise training improves health-related physical fitness and patient-reported
      outcomes in cancer survivors, but few interventions have targeted colorectal
      cancer (CRC) survivors. This investigation aimed to determine the feasibility and
      efficacy of a 12-week supervised exercise training program for CRC survivors.
      Feasibility was assessed by tracking participant recruitment, loss to follow-up,
      assessment completion rates, participant evaluation, and adherence to the
      intervention. Efficacy was determined by changes in health-related physical
      fitness. Over a 1-year period, 72 of 351 (21%) CRC survivors screened were
      eligible for the study and 29 of the 72 (40%) were enrolled. Two participants
      were lost to follow-up (7%) and the completion rate for all study assessments was
      >=93%. Mean adherence to the exercise intervention was 91% (standard deviation =
      +/-18%), with a median of 98%. Participants rated the intervention positively
      (all items >= 6.6/7) and burden of testing low (all tests <= 2.4/7). Compared
      with baseline, CRC survivors showed improvements in peak oxygen uptake (mean
      change (MC) = +0.24 L.min(-1), p < 0.001), upper (MC = +7.0 kg, p < 0.001) and
      lower (MC = +26.5 kg, p < 0.001) body strength, waist circumference (MC = -2.1
      cm, p = 0.005), sum of skinfolds (MC = -7.9 mm, p = 0.006), and trunk forward
      flexion (MC = +2.5 cm, p = 0.019). Exercise training was found to be feasible and
      improved many aspects of health-related physical fitness in CRC survivors that
      may be associated with improved quality of life and survival in these
      individuals. 

PMID- 24869977
TI  - The effects of a 6-month resistance training and dried plum consumption
      intervention on strength, body composition, blood markers of bone turnover, and
      inflammation in breast cancer survivors.
AB  - The purpose of this study was to examine the effects of resistance training (RT)
      and dried plum (DP) consumption on strength, body composition, blood markers of
      bone, and inflammation in breast cancer survivors (BCS). Twenty-three BCS (RT, n
      = 12; RT+DP, n = 11), aged 64 +/- 7 years, were evaluated at baseline and after 6
      months of intervention on the following: muscular strength (chest press and leg
      extension) via 1-repetition maximums (1RMs); body composition, specifically bone
      mineral density (BMD) by dual energy X-ray absorptiometry; biochemical markers of
      bone turnover (bone-specific alkaline phosphatase (BAP), tartrate resistant acid
      phosphatase (TRAP-5b)); and inflammation (C-reactive protein (CRP)). Target RT
      prescription was 2 days/week of 10 exercises, including 2 sets of 8-12
      repetitions at ~60%-80% of 1RM. RT+DP also consumed 90 g of DP daily. There were
      no baseline differences between groups or any group-by-time interactions for any
      of the variables. BCS increased upper (p < 0.05) (RT: 64 +/- 14 to 80 +/- 17 kg;
      RT+DP: 72 +/- 23 to 91 +/- 20 kg) and lower (p < 0.05) (RT: 69 +/- 20 to 87 +/-
      28 kg; RT+DP: 78 +/- 19 to 100 +/- 21 kg) body strength. Body composition and BMD
      improvements were not observed. TRAP-5b decreased in the RT group (p < 0.05)
      (4.55 +/- 1.57 to 4.04 +/- 1.63 U/L) and the RT+DP group (p = 0.07) (5.10 +/-
      2.75 to 4.27 +/- 2.03 U/L). Changes in BAP and CRP were not observed. RT was
      effective for improving biochemical markers of bone turnover and muscular
      strength in BCS. A longer and higher intensity intervention may be needed to
      reveal the true effects of RT and DP on body composition and biochemical markers
      of inflammation. 

PMID- 24869976
TI  - Relationship between exercise behavior, cardiorespiratory fitness, and cognitive
      function in early breast cancer patients treated with doxorubicin-containing
      chemotherapy: a pilot study.
AB  - The purpose of this study was to examine the relationship between self-reported
      exercise behavior, cardiorespiratory fitness (CRF), and cognitive function in
      early breast cancer patients. Thirty-seven breast cancer patients following
      completion of chemotherapy (median 16 months) and 14 controls were studied.
      Cognitive function was assessed using the Central Nervous System (CNS) Vital
      Signs software (CNS Vital Signs, LLC, Morrisville, N.C., USA), a computerized
      test battery consisting of 9 cognitive subtests. Exercise behavior was evaluated
      using the Godin Leisure Time Exercise Questionnaire, and CRF was assessed via a
      cardiopulmonary exercise test to assess peak oxygen consumption. Patients' mean
      total exercise was 184 +/- 141 min.week(-1) compared with 442 +/- 315 min.week(
      1) in controls (p < 0.001). Significantly fewer patients (32%) were meeting
      exercise guidelines (i.e., >=150 min of moderate-intensity or vigorous exercise
      per week) compared with 57% of controls (p = 0.014). Patients' peak oxygen
      consumption averaged 23.5 +/- 6.3 mL.kg(-1).min(-1) compared with 30.6 +/- 7.0
      mL.kg(-1).min(-1) in controls (p < 0.01). Scores on the cognitive subdomains were
      generally lower in patients compared with controls, although only the difference
      in verbal memory was significant (unadjusted p = 0.041). In patients, weak to
      moderate correlations were indicated between exercise, peak oxygen consumption,
      and the majority of cognitive subdomain scores; however, there was a significant
      positive correlation between exercise and visual memory (r = 0.47, p = 0.004). In
      conclusion, breast cancer patients following the completion of primary adjuvant
      chemotherapy exhibit, in general, worse cognitive performance than healthy women
      from the general population, and such performance may be related to their level
      of exercise behavior. 

PMID- 24869979
TI  - Special Issue: The role of diet, body composition, and physical activity on
      cancer prevention, treatment, and survivorship.

PMID- 24869980
TI  - Relationship between nutritional profile, measures of adiposity, and bone mineral
      density in postmenopausal Saudi women.
AB  - BACKGROUND: Osteoporosis remains a major health problem in all developed
      countries and is a condition in which several dietary factors have been
      implicated. OBJECTIVE: To assess the nutritional status and levels of adiposity
      of postmenopausal women in relation to bone mineral density. DESIGN: A cross
      sectional study in which dietary intake was estimated by a food frequency
      questionnaire in 300 Saudi postmenopausal women aged 46-88 years. Bone profile
      biochemistry (serum calcium, phosphate, parathyroid hormone [PTH], vitamin D) and
      bone mineral density (BMD) in 3 skeletal sites were determined for all
      participants. RESULTS: Overweight and obesity were highly prevalent among the
      study population. No significant correlation was found between dietary calcium
      and vitamin D and bone mass at any site. Dietary intake of calcium and vitamin D
      was significantly less than the recommended levels for a large proportion of the
      cohort. Energy-adjusted intakes of carbohydrates, fat, protein, and unsaturated
      fatty acids were associated with BMD in the postmenopausal women. Age, body
      weight, and residency type were predictors of BMD at all sites. Serum-intact PTH
      was a predictor of BMD at lumbar spine and femoral neck. Waist : hip ratio (WHR)
      was a predictor for BMD at femoral neck. CONCLUSIONS: These results suggest that
      BMD is influenced by dietary factors other than calcium and vitamin D. However,
      nondietary factors such as age, WHR, PTH, and body weight may be important
      determinants of BMD in postmenopausal women.

PMID- 24869981
TI  - Subchronic toxicity and immunotoxicity of MeO-PEG-poly(D,L-lactic-co-glycolic
      acid)-PEG-OMe triblock copolymer nanoparticles delivered intravenously into rats.
AB  - Although monomethoxy(polyethyleneglycol)-poly (D,L-lactic-co-glycolic acid)
      monomethoxy (PELGE) nanoparticles have been widely studied as a drug delivery
      system, little is known about their toxicity in vivo. Here we examined the
      subchronic toxicity and immunotoxicity of different doses of PELGE nanoparticles
      with diameters of 50 and 200 nm (PELGE50 and PELGE200) in rats. Neither size of
      PELGE nanoparticles showed obvious subchronic toxic effects during 28 d of
      continuous intravenous administration based on clinical observation, body weight,
      hematology parameters and histopathology analysis. PELGE200 nanoparticles showed
      no overt signs of immunotoxicity based on organ coefficients, histopathology
      analysis, immunoglobulin levels, blood lymphocyte subpopulations and splenocyte
      cytokines. Conversely, PELGE50 nanoparticles were associated with an increased
      organ coefficient and histopathological changes in the spleen, increased serum
      IgM and IgG levels, alterations in blood lymphocyte subpopulations and enhanced
      expression of spleen interferon-gamma. Taken together, these results suggest that
      PELGE nanoparticles show low subchronic toxicity but substantial immunotoxicity,
      which depends strongly on particle size. These findings will be useful for safe
      application of PELGE nanoparticles in drug delivery systems.

PMID- 24869982
TI  - Carbohydrate-protein interactions that drive processive polysaccharide
      translocation in enzymes revealed from a computational study of cellobiohydrolase
      processivity.
AB  - Translocation of carbohydrate polymers through protein tunnels and clefts is a
      ubiquitous biochemical phenomenon in proteins such as polysaccharide synthases,
      glycoside hydrolases, and carbohydrate-binding modules. Although static snapshots
      of carbohydrate polymer binding in proteins have long been studied via
      crystallography and spectroscopy, the molecular details of polysaccharide chain
      processivity have not been elucidated. Here, we employ simulation to examine how
      a cellulose chain translocates by a disaccharide unit during the processive cycle
      of a glycoside hydrolase family 7 cellobiohydrolase. Our results demonstrate that
      these biologically and industrially important enzymes employ a two-step mechanism
      for chain threading to form a Michaelis complex and that the free energy barrier
      to chain threading is significantly lower than the hydrolysis barrier. Taken with
      previous studies, our findings suggest that the rate-limiting step in enzymatic
      cellulose degradation is the glycosylation reaction, not chain processivity.
      Based on the simulations, we find that strong electrostatic interactions with
      polar residues that are conserved in GH7 cellobiohydrolases, but not in GH7
      endoglucanases, at the leading glucosyl ring provide the thermodynamic driving
      force for polysaccharide chain translocation. Also, we consider the role of
      aromatic-carbohydrate interactions, which are widespread in carbohydrate-active
      enzymes and have long been associated with processivity. Our analysis suggests
      that the primary role for these aromatic residues is to provide tunnel shape and
      guide the carbohydrate chain to the active site. More broadly, this work
      elucidates the role of common protein motifs found in carbohydrate-active enzymes
      that synthesize or depolymerize polysaccharides by chain translocation mechanisms
      coupled to catalysis. 

PMID- 24869983
TI  - An imaging study of the compressed area, bony fragment area, and the total
      fracture-involved area in thoracolumbar burst fractures.
AB  - STUDY DESIGN: Imaging study. SUMMARY OF BACKGROUND DATA: X-ray and computed
      tomography (CT) sagittal reconstruction images are used to evaluate the stability
      of the spine. However, we did not know the extent of difference between them.
      OBJECTIVE: The aim of the study was to compare the differences seen in
      thoracolumbar burst fractures on lateral radiographs and CT sagittal
      reconstruction images and investigate their clinical relevance. MATERIALS AND
      METHODS: Lateral radiographs and CT sagittal reconstruction images of 45 patients
      with thoracolumbar burst fractures were used to record the following
      measurements: the compressed area of the fractured vertebrae, from lateral
      radiographs, and the sagittal compressed area, bony fragment area, and total
      fracture-involved area, from CT sagittal reconstruction images. RESULTS: The
      percentage of compressed area of fractured vertebrae was 29.32+/-13.80% on
      lateral radiographs and 27.93+/-12.21% on CT sagittal reconstruction images;
      there was no significant difference between them (P>0.05). The percentage of
      total fracture-involved area was 53.20+/-20.64% on CT sagittal reconstruction
      images, higher than the compressed area measured on lateral radiographs (P<0.01)
      and CT sagittal reconstruction images (P<0.01). The percentage of bony fragment
      area was 25.27+/-15.18% on CT sagittal reconstruction images; there was no
      significant relationship between bony fragment area and the compressed area
      (r=0.1258, P>0.05). CONCLUSIONS: The compressed area of fractured vertebrae on
      lateral radiographs could not represent the fracture-involved area and
      underestimated the total fracture-involved area. We suggested that the above 3
      parameters could be easily obtained on CT sagittal reconstruction images, which
      might be better for assessing the potential instability of the thoracolumbar
      burst fracture and could become a valuable and indispensable examination for
      therapeutic decision making.

PMID- 24869984
TI  - Surgical anatomy of the diaphragm in the anterolateral approach to the spine: a
      cadaveric study.
AB  - STUDY DESIGN: Laboratory cadaveric study. OBJECTIVE: To delineate the pertinent
      surgical anatomy of the diaphragm during access to the anterolateral
      thoracolumbar junction. SUMMARY OF BACKGROUND DATA: The general anatomy of the
      thoracic diaphragm is well described. The specific surgical anatomy as it
      pertains to the lateral and thoracoabdominal approaches to the thoracolumbar
      junction is not well described. METHODS: Dissections were performed on adult
      fresh cadaveric specimens. Special attention was paid to the diaphragmatic
      attachments to the lower rib cage and to the spinal thoracolumbar junction.
      RESULTS: The pertinent diaphragmatic attachments to the rib cage are at the 11th
      and 12th ribs. Whether the diaphragm is incised or mobilized ventrally, the
      pertinent spinal attachments are the lateral and medial arcuate ligaments.
      Identifying and sectioning these structures allows for direct access to the
      thoracolumbar junction, particularly the L1 vertebral body. CONCLUSIONS: An
      understanding of the diaphragmatic-costal and diaphragmatic-spinal attachments is
      key for the safe and effective implementation of diaphragm mobilization during
      the lateral and thoracoabdominal approaches to the spine.

PMID- 24869985
TI  - Biomechanical analysis of various footprints of transforaminal lumbar interbody
      fusion devices.
AB  - STUDY DESIGN: A biomechanical finite element modeling study of the human lumbar
      spine. OBJECTIVE: To evaluate the effects of a transforaminal interbody device's
      footprint on lumbar spine biomechanics to further examine the potential subtle
      biomechanical differences not captured in previous studies. SUMMARY OF BACKGROUND
      DATA: In recent years, the evolution of interbody fusion devices has provided the
      surgeons with a multitude of options. An articulating transforaminal lumbar
      interbody fusion (TLIF) device is developed to overcome the surgical challenges
      associated with insertion of a large footprint interbody device through a small
      incision. METHODS: A finite element model of the L3-S1 lumbar segment was
      modified to simulate replacement of various TLIF constructs with different cage
      designs including an articulating vertebral interbody (AVID) TLIF device and a
      generic TLIF device placed in different configurations. The instrumented models
      were subjected to a 400 N follower load along with a 10 N m bending moment at
      different physiological planes. The kinematics, loads, and stresses were compared
      among various models. RESULTS: Simulated cage designs provided similar
      kinematical stability within the treated segments. However, the articulating and
      double TLIF implants allowed for better load sharing through the anterior column.
      These implants resulted in lower endplate and pedicle screw stresses and in more
      homogenous stress distribution across the peripheral region of the endplate.
      CONCLUSIONS: An articulating, large footprint, peripherally placed TLIF device
      affords substantial biomechanical advantages. This device may be able to reduce
      the incidence of subsidence because of its ability to reduce and distribute the
      endplate stresses in the stronger peripheral region. It may also reduce the
      posterior hardware failure incidence owing to its ability to reduce the screw
      stresses as compared with traditional TLIF. Although double TLIF has been
      demonstrated to have similar biomechanical advantages as the AVID, complications
      associated with double TLIF (ie, larger surgical incision, longer surgical
      procedure, placement and alignment challenges) support AVID as a better optimized
      alternative.

PMID- 24869986
TI  - MRI evaluation of lumbar endplate and facet erosion in rheumatoid arthritis.
AB  - STUDY DESIGN: A cross-sectional study. OBJECTIVE: This study was aimed to
      quantify the extent of lumbar endplate and facet joint erosion in patients with
      rheumatoid arthritis (RA) using magnetic resonance imaging, to calculate the
      prevalence of erosion, and sought correlated factors. SUMMARY OF BACKGROUND DATA:
      Few studies have examined the lumbar spine in RA, especially the relationship
      between endplate and facet joint erosions and lumbar lesions induced by RA.
      METHODS: A total of 201 patients with RA were enrolled. Lumbar endplate and facet
      joint erosion were defined as irregularities and low-intensity change on magnetic
      resonance imaging, and graded utilizing the Rheumatoid Arthritis Magnetic
      Resonance Imaging Score. Lumbar lesions were defined as scoliosis,
      spondylolisthesis, and vertebral fracture on plain x-ray. Multivariable logistic
      regression analysis was used to seek correlations between the erosion and spinal
      level, RA-related factors and x-ray findings. RESULTS: Lumbar endplate and facet
      erosion were detected in 70.6% and 76.6% of individuals, respectively, and at
      33.8% and 38.7% of lumbar intervertebral levels, respectively. The severity of
      erosion in individual patients correlated with lumbar lesions. Endplate and facet
      erosion at each level correlated with high disease activity, and were most common
      at mid-lumbar and lower-lumbar levels. Strong correlations were observed between
      endplate erosion and adjacent vertebral body fracture or disk degeneration, and
      between facet erosion and spondylolisthesis. CONCLUSIONS: Lumbar endplate and
      facet erosion are common in RA, and are observed more frequently at mid-low
      levels and when RA is poorly controlled. This pattern of erosion may play a
      crucial role in the generation of lumbar lesions in RA.

PMID- 24869987
TI  - Quantification of changes in gait characteristics associated with intermittent
      claudication in patients with lumbar spinal stenosis.
AB  - STUDY DESIGN: Cross-sectional observational study. OBJECTIVE: To quantify changes
      in gait characteristics associated with claudication after continuous walking,
      and to investigate the relationship between walking capacity and gait
      characteristics in patients with lumbar spinal stenosis (LSS). SUMMARY OF
      BACKGROUND DATA: Walking difficulty due to pain or neurological symptoms
      accompanied by continuous walking may have negative effects on gait
      characteristics in patients with LSS. However, there are few detailed reports on
      the association of these changes with intermittent claudication and their
      relationship with walking capacity. METHODS: For this study, 11 LSS patients with
      intermittent claudication were recruited. The subjects continued walking until
      they expressed a difficulty in continuing further. Postural sway, autocorrelation
      peak (AC), stride frequency (SF), and coefficient of variance (CV) were analyzed
      using accelerometers. To detect changes in gait parameters, we compared
      acceleration at the start and at the end of the walking task. RESULTS: Walking
      difficulty during the test increased from 4 (interquartile range, 1-5) to 9
      (interquartile range, 7-10). The postural sway significantly increased after the
      onset of maximum walking difficulty. AC, SF, or CV did not show significant
      change. Maximum walking distance significantly correlated with postural sway at
      the cervical sensor (r=-0.64), and CV (rho=-0.66), an index of gait variability,
      at the beginning of the walking task. CONCLUSIONS: The change in gait parameters
      associated with claudication during continuous walking is detectable using
      accelerometers. Postural sway increases after the provocation of walking
      difficulty due to pain or neurological symptoms. In addition, walking capacity
      correlated with postural sway of the upper trunk and gait variability during
      walking initiation. This methodology warrants further studies to confirm its
      usefulness as an assessment tool for patients with LSS.

PMID- 24869988
TI  - Liver developed entirely outside the abdominal cavity in adult omphalocele.

PMID- 24869989
TI  - Large "pedunculated" colonic lipoma: a word of caution while cutting into fat!

PMID- 24869990
TI  - Knowledge and attitudes of students towards viral hepatitis B and C at the
      University of Lome.

PMID- 24869991
TI  - Four cases of adenocarcinoma of esophagus with co-existing hydatid cyst of liver
      which caused delayed management of carcinoma esophagus.

PMID- 24869992
TI  - The classic melanosis coli.

PMID- 24869993
TI  - Factors relating to stages of change in walking exercise behavior among older
      adults living in a hilly, mountainous area.
AB  - OBJECTIVES: We sought to identify factors relating to stages of change in walking
      exercise behavior among older adults living in a hilly, mountainous area in
      search of effective interventions to aid transitions. METHODS: An anonymous self
      administered questionnaire survey was conducted with all older adults aged
      between 60 and 74 years (n=752) living in Takahashi City in the district of
      Kawakami, Okayama Prefecture. Questionnaires were distributed by local volunteer
      staff to 752 older adults, who completed and mailed the questionnaires to the
      principal investigator. Data on participants' demographic characteristics
      (gender, age, family structure, etc.), stages of change in walking exercise
      behavior, self-efficacy, perceived physical environment, and perceived social
      environment were collected through the survey. The participants were divided into
      non-walking, preparation, and walking subgroups. The chi(2), Kruskal-Wallis, Mann
      Whitney U, and Bonferroni's multiple comparison tests were performed.
      Significance was set at 0.05. RESULTS: of 325 returned questionnaires (response
      rate, 43.2%), 164 completed questionnaires were analyzed. Females were
      significantly more likely to be physically active than were males. The
      preparation group had the largest number of participants (n=69, 42.1%), while the
      walking group had the smallest (n=43, 26.2%). The Kruskal-Wallis test revealed
      differences between stages of change in walking exercise behavior in terms of
      self-efficacy, perceived physical environment (landscape), and perceived social
      environment (all items). Multiple comparisons revealed that there were
      significant differences between the non-walking and preparation groups in self
      efficacy, landscape, and advice/guidelines, while there were significant
      differences between the preparation and walking groups in self-efficacy and
      understanding/empathy. CONCLUSION: Moving through the stages of change in walking
      exercise behavior was associated with gender, self-efficacy, the physical
      environment (landscape), and all components of the social environment. These
      findings suggest that in order to help older adults transition successfully
      through these stages of change, it is necessary to implement individualized
      interventions with due regard to landscape preservation, social environment, and
      self-efficacy, as well as participants' current stage of change.

PMID- 24869994
TI  - Exploring the link between standard lifestyle questionnaires administered during
      specific medical check-ups and incidence of metabolic syndrome in Chiba
      Prefecture.
AB  - OBJECTIVES: The aim of this study was to clarify the relationship between
      standard lifestyle questionnaires and the development of metabolic syndrome
      (MetS). METHODS: We analyzed the data on 278,989 people (111,524 males and
      167,465 females) living in Chiba Prefecture who underwent consecutive medical
      check-ups in 2008 and 2009. The standard lifestyle questionnaire administered
      during the check-ups consisted of 10 items, including three on exercise
      behaviors, four on dietary behaviors, and one each on drinking, smoking, and
      sleeping behaviors. An individual was assigned to the "developing MetS" category
      if there was no diagnosis of MetS in 2008, followed by a diagnosis of MetS or pre
      MetS in 2009. We calculated the odds ratios for developing MetS adjusted for
      gender and age. Developing MetS was the dependent factor in a multiple logistic
      regression analysis used to examine its relationship to responses on the
      lifestyle questionnaire. RESULTS: In men, the odds of developing MetS were
      significantly lower for participants who exercised regularly ("walking fast,"
      OR=0.88, 95% CI [0.83-0.93]; and "higher physical activity," 0.85, [0.80-0.90]),
      but were significantly higher for those who engaged in _ dietary behaviors and
      drinking ("eating fast," 1.49, [1.40-1.59]; "having a habit of eating late-night
      snacks," 1.15, [1.05-1.27]; "having a late night meal," 1.15, [1.08-1.23]; and
      "drinking every night," 1.08, [1.02-1.14]). In women, the odds of developing MetS
      were significantly lower for subjects who reported engaging in regular exercise
      and drinking ("walking fast," 0.74, [0.70-0.78]; "higher physical activity,"
      0.92, [0.87-0.98]; and "drinking every night," 0.80, [0.71-0.90]), but were
      significantly higher for those who had such dietary behaviors as "eating fast"
      (1.48, [1.39-1.58]), "having a habit of eating late-night snacks" (1.15, [1.05
      1.26]), "having a late night meal" (1.19, [1.10-1.29]), and "not having
      breakfast" (1.21, [1.07-1.36]). CONCLUSION: These results show that poor dietary
      or exercise habits as determined by the standard lifestyle questionnaire were
      associated with the development of MetS.

PMID- 24869995
TI  - Development of a health literacy scale for women of reproductive age: an
      examination of reliability and validity in a study of female workers.
AB  - OBJECTIVES: This study aimed to develop a Health Literacy Scale for women of
      reproductive age by creating an original scale based on a concept analysis of
      health literacy. METHODS: A 30-item scale was created through an examination of
      their content validity and face validity based on attributes derived from concept
      analysis conducted in previous research. The main survey consisted of a self
      administered questionnaire distributed to 1,030 female workers between the ages
      of 20 and 39 residing in the Kinki and Tokai regions of Japan. An additional
      survey was administered to 424 participants, from whom written informed consent
      was obtained. The reliability of the scale was examined using Cronbach's alpha
      and by assessing the significance of the correlation coefficient with the
      additional survey. Validity was examined through a comparison with the Japanese
      version of the Health Promoting Lifestyle Profile (JLV-HPLP II) and by examining
      correlations with subscale scores of the Social Skills Self-Rating Scale for
      adults as well as scale scores for cervical cancer screening behaviors. RESULTS:
      For the main survey, 632 out of 1,030 (61.4%) responded, of which 622 (98.4%)
      were valid responses. For the additional survey, 86 out of 424 (20.3%) responded,
      of which 86 (100%) were valid responses. The original 30 items were reduced to 21
      across four factors through item and factor analysis using the principal
      extraction method and promax rotation. The coefficient of determination was
      0.537. These four factors were labeled: "Women's choice for adopting health
      information and practice," "Self-care during menstruation," "Knowledge of the
      female body," and "Sexual discussion with partner." Cronbach's alpha for each
      factor ranged from 0.72 to 0.83, and the overall value was 0.88. For the
      additional survey, the correlation on the overall scale was significant (r=0.85,
      P<0.01). Moreover, the new scale was significantly correlated with the JLV-HPLP
      II and the Social Skills Self-Rating Scale for adults (ps<0.01). The correlation
      with scale scores for cervical cancer screening behaviors was highly significant
      among those who had been screened (P<0.001). CONCLUSION: The reliability and
      validity of this particular Health Literacy Scale were largely confirmed. The
      significant relationship observed between cervical cancer screening behaviors and
      the various scale scores suggests the practical applicability of health literacy
      education aimed at the prevention, early detection, and treatment of female
      specific diseases.

PMID- 24869996
TI  - The Madagascan endemic myrmicine ants related to Eutetramorium (Hymenoptera:
      Formicidae): taxonomy of the genera Eutetramorium Emery, Malagidris nom. n.,
      Myrmisaraka gen. n., Royidris gen. n., and Vitsika gen. n.
AB  - The monophyletic group of myrmicine ant genera related to Eutetramorium is
      described and its taxonomy is documented. The group is endemic in Madagascar and
      contains five genera: Eutetramorium Emery, 1899 (3 species, 1 of which is new);
      Malagidris nom. n., a replacement name for Brunella Forel, 1917, junior homonym
      of Brunella Smith, G.W. 1909 (Crustacea) (6 species, 5 of which are new);
      Myrmisaraka gen. n. (2 species, both new); Royidris gen. n. (15 species, 11 of
      which are new); Vitsika gen. n. (14 species, all of which are new). Keys to the
      worker caste are provided for all genera, and provisional keys to known males are
      given for Malagidris and Vitsika. 

PMID- 24869997
TI  - Dryinidae of the Neotropical region (Hymenoptera: Chrysidoidea).
AB  - An updated revision of Neotropical Dryinidae is presented. Seven subfamilies, 23
      genera and 502 species are treated. Descriptions, geographic distribution, known
      hosts, natural enemies and type material of each species are presented, together
      with illustrations of the main morphological characters and keys to the
      subfamilies, genera and species. Complete lists of references concerning the
      Neotropical Dryinidae and their hosts are given. A new genus Peckius Olmi &
      Virla, gen. nov. (type species Peckius insularis Olmi & Virla, sp. nov.)
      (subfamily Apodryininae) is described. The following eleven new species are
      described: Anteon xochipalense Olmi & Virla, sp. nov. (Mexico, Guerrero),
      Deinodryinus levigatus Olmi & Virla, sp. nov. (Peru, Lamabayeque), Deinodryinus
      xanthonotatus Olmi & Virla, sp. nov. (French Guiana), Dryinus semiruber Olmi &
      Virla, sp. nov. (Argentina, Corrientes), Dryinus valens Olmi & Virla, sp. nov.
      (Dominican Republic, Pedernales), Dryinus xanthopus Olmi & Virla, sp. nov.
      (French Guiana), Megadryinus cacaonis Olmi & Virla, sp. nov. (Brazil, Sao Paulo),
      Gonatopus isabelensis Olmi & Virla, sp. nov. (Ecuador, Galapagos Islands),
      Gonatopus villamilensis Olmi & Virla, sp. nov. (Ecuador, Galapagos Islands),
      Neodryinus mayanus Olmi & Virla, sp. nov. (Honduras), and Peckius insularis Olmi
      & Virla, sp. nov. (Ecuador, Galapagos Islands). The following new synonymies are
      presented: Deinodryinus kawensis Olmi 2011b (April) (=D. caxiuana Coelho, Aguiar
      & Engel, 2011 (June), syn. nov.); Dryinus gibbosus Olmi, 1984 (=D. multicarinatus
      Coelho, Aguiar & Engel, 2011, syn. nov.); Dryinus striatus (Fenton, 1927) (=D.
      sinopensis Olmi, 1984, syn. nov.; =D. cerrensis Olmi, 2004a, syn. nov.);
      Gonatopus Ljungh, 1810 (=Trichogonatopus Kieffer, 1909, syn. nov.); Eucamptonyx
      dromedarius (Cameron 1888) (=E. hansoni Olmi, 1991, syn. nov.); Haplogonatopus
      hernandezae Olmi, 1984 (=H. crucianus Olmi, 1986, syn. nov.). The following new
      combinations are proposed: Eucamptonyx dromedarius (Cameron, 1888), comb. nov.
      (from Gonatopus); Gonatopus goiasensis (Olmi 1991), comb. nov. (from
      Trichogonatopus); G. hispidus (Olmi 1984), comb. nov. (from Trichogonatopus); G.
      longinoi (Olmi, 1998d), comb. nov. (from Trichogonatopus); G. marinoae (Virla,
      1997), comb. nov. (from Trichogonatopus); G. neotropicus (Olmi, 1984), comb. nov.
      (from Trichogonatopus); G. raptor (Fenton, 1927), comb. nov. (from
      Chalcogonatopus); G. rubriceps (Kieffer, 1909), comb. nov. (from
      Trichogonatopus); G. stellaris (Virla, 1997), comb. nov. (from Trichogonatopus).
      The male of Crovettia brasiliana Olmi 1984, is described for the first time.

PMID- 24870000
TI  - Lightweight, highly compressible, noncrystalline cellulose capsules.
AB  - We demonstrate how to prepare extraordinarily deformable, gas-filled, spherical
      capsules from nonmodified cellulose. These capsules have a low nominal density,
      ranging from 7.6 to 14.2 kg/m(3), and can be deformed elastically to 70%
      deformation at 50% relative humidity. No compressive strain-at-break could be
      detected for these dry cellulose capsules, since they did not rupture even when
      compressed into a disk with pockets of highly compressed air. A quantitative
      constitutive model for the large deformation compression of these capsules is
      derived, including their high-frequency mechanical response and their low
      frequency force relaxation, where the latter is governed by the gas barrier
      properties of the dry capsule. Mechanical testing corroborated these models with
      good accuracy. Force relaxation measurements at a constant compression rendered
      an estimate for the gas permeability of air through the capsule wall, calculated
      to 0.4 mL MUm/m(2) days kPa at 50% relative humidity. These properties taken
      together open up a large application area for the capsules, and they could most
      likely be used for applications in compressible, lightweight materials and also
      constitute excellent model materials for adsorption and adhesion studies. 

PMID- 24870001
TI  - [Inequality in primary care interventions in maternal and child health care in
      Mexico].
AB  - OBJECTIVE: To analyze the principal indicators associated with maternal mortality
      and mortality in children under 1 year of age and evaluate coverage levels and
      variability among the federative entities of Mexico. METHODS: Eight interventions
      in maternal and child primary health care (variables) were studied: complete
      vaccination series, measles vaccine, and pentavalent vaccine in children under 1
      year of age; early breast-feeding; prenatal care with at least one check-up by
      trained staff; prevalence of contraceptive use among married women of
      reproductive age; obstetric care in delivery by trained staff; and the
      administration of tetanus toxoid (TT) to pregnant women. The average and standard
      deviation of national coverage for each variable was calculated. Within each
      federative entity the proportion of municipalities with high, medium, and low
      marginalization was determined. States were ranked by the proportion of
      municipalities with high marginalization (highest to lowest) and divided into
      quintiles. Absolute inequality was measured using the observed difference and
      relative inequality, using the ratio of each variable studied. RESULTS: The
      average national coverage for the eight variables studied ranged from 86.5% to
      97.5%, with administration of TT to pregnant women the lowest and administration
      of measles vaccine to children under 1 year of age the highest. Obstetric care in
      delivery, prevalence of contraceptive use, and prenatal checkup were the
      variables with less equitable coverage. In states with higher levels of
      marginalization, activities dependent on a structured health system-e.g.,
      obstetric care in delivery-showed lower levels of coverage compared to preventive
      activities not requiring costly inputs or infrastructure-e.g., early breast
      feeding. CONCLUSIONS: Interventions exhibiting greater inequity are associated
      with the lack of medical infrastructure and are more accentuated in federative
      entities with higher levels of marginalization. Greater public health expenditure
      is urgently needed to implement feasible, effective alternatives in terms of
      access and health care. Intersectoral policies and activities should be
      implemented to create synergies that will equitably improve the health of Mexican
      mothers and children.

PMID- 24869998
TI  - Retinal chromophore structure and Schiff base interactions in red-shifted
      channelrhodopsin-1 from Chlamydomonas augustae.
AB  - Channelrhodopsins (ChRs), which form a distinct branch of the microbial rhodopsin
      family, control phototaxis in green algae. Because ChRs can be expressed and
      function in neuronal membranes as light-gated cation channels, they have rapidly
      become an important optogenetic tool in neurobiology. While channelrhodopsin-2
      from the unicellular alga Chlamydomonas reinhardtii (CrChR2) is the most commonly
      used and extensively studied optogenetic ChR, little is known about the
      properties of the diverse group of other ChRs. In this study, near-infrared
      confocal resonance Raman spectroscopy along with hydrogen-deuterium exchange and
      site-directed mutagenesis were used to study the structure of red-shifted ChR1
      from Chlamydomonas augustae (CaChR1). These measurements reveal that (i) CaChR1
      has an all-trans-retinal structure similar to those of the light-driven proton
      pump bacteriorhodopsin (BR) and sensory rhodopsin II but different from that of
      the mixed retinal composition of CrChR2, (ii) lowering the pH from 7 to 2 or
      substituting neutral residues for Glu169 or Asp299 does not significantly shift
      the ethylenic stretch frequency more than 1-2 cm(-1) in contrast to BR in which a
      downshift of 7-9 cm(-1) occurs reflecting neutralization of the Asp85 counterion,
      and (iii) the CaChR1 protonated Schiff base (SB) has stronger hydrogen bonding
      than BR. A model is proposed to explain these results whereby at pH 7 the
      predominant counterion to the SB is Asp299 (the homologue to Asp212 in BR) while
      Glu169 (the homologue to Asp85 in BR) exists in a neutral state. We observe an
      unusual constancy of the resonance Raman spectra over the broad range from pH 9
      to 2 and discuss its implications. These results are in accord with recent
      visible absorption and current measurements of CaChR1 [Sineshchekov, O. A., et
      al. (2013) Intramolecular proton transfer in channelrhodopsins. Biophys. J. 104,
      807-817; Li, H., et al. (2014) Role of a helix B lysine residue in the
      photoactive site in channelrhodopsins. Biophys. J. 106, 1607-1617]. 

PMID- 24870002
TI  - [Construction of a development index for young people aged 14 - 26 in Medellin,
      Colombia].
AB  - OBJECTIVE: To construct and validate a Medellin youth development index (IDJM,
      for its Spanish acronym) covering young people aged 14 - 26 residing in the
      city's comunas and corregimientos, thus contributing scientific evidence for the
      development of intervention strategies. METHODS: A cross-sectional study of a
      random representative sample of 8 001 young people residing in Medellin,
      Colombia, was conducted, to whom a validated instrument was applied whose
      dimensions provide information on youth development. The Prinqual method for
      processing qualitative variables through optimal quantification was used. The
      first main component, the IDJM, was selected by means of a categorical analysis
      of the main components. The index was validated and disaggregated by sex, age
      group, and each dimension studied. RESULTS: The average IDJM score was 74.4
      (SD=9.8; CI95%: 74.2 - 74.6). The 14 - 17-year-old age group had the highest
      score, with females exhibiting slightly higher scores than their male
      counterparts. The analysis likewise showed that scores increased with
      socioeconomic level and decreased as the age of the study population increased.
      Education was the dimension that contributed the most to the index, followed by
      Goods and Services, while Democracy and Participation and Labor contributed the
      least across all age groups. CONCLUSIONS: A Medellin youth development index was
      constructed and validated. It should prove to be a very useful tool, especially
      for decision-making regarding public policies that target young people. It is
      essential that the IDJM be updated regularly to ensure accurate assessment of the
      interventions' impact, especially in the dimensions that contributed lower
      scores.

PMID- 24870003
TI  - Contribution of Mexico's Universal Immunization Program to the Fourth Millennium
      Development Goal.
AB  - OBJECTIVE: To identify and describe 1) progress achieved thus far in meeting the
      commitments of the Fourth Millennium Development Goal (MDG 4) in Mexico, mainly
      the contribution of the Universal Immunization Program (UIP) over the last 20
      years, and 2) new opportunities for further reducing mortality among children
      under 5 years old. METHODS: An observational, descriptive, retrospective study
      was carried out to examine registered causes of death in children under 5 between
      1990 and 2010. Indicators were built according to the recommendations of the
      United Nations. RESULTS: In 2010, deaths among children under 5 decreased 64.3%
      compared to the baseline (1990) figure. Of the total deaths of the children under
      5, the neonatal period was the most affected (52.8%), followed by the 1 to 11
      months (30.9%), and the 12 to 59 months (16.2%) groups. A 34% overall mortality
      reduction was observed after the universalization of immunization against
      influenza, rotavirus, and pneumococcus in children under 5. CONCLUSIONS: Despite
      a significant reduction in under-5 mortality in Mexico over the last 20 years,
      largely due to the successes of the UIP, several challenges remain, particularly
      in improving preventive and curative services during pre- and postnatal care.

PMID- 24870004
TI  - [Depression in former slave communities in Brazil: screening and associated
      factors].
AB  - OBJECTIVE: To assess the prevalence and the factors associated with positive
      screening for major depressive episode (MDE) in former slave communities in the
      state of Bahia, Brazil. METHODS: In this population-based, cross-sectional study,
      764 participants were randomly selected from five former slave communities in
      Vitoria da Conquista, Bahia, Brazil. Depression was defined as a cutoff score of
      10 or more points and the presence of five or more symptoms according to the
      Patient Health Questionnaire (PHQ-9). Poisson regression was used to assess
      prevalence ratios (PR), with a 95% confidence interval (95%CI). RESULTS:
      Screening for MDE was positive in 12% of participants (95%CI: 10 - 14%), but only
      2.3% reported a previous diagnosis. Depression was associated with self-reported
      poor or very poor health status (PR = 1.14; 95%CI: 1.04 - 1.26), chronic disease
      (PR = 1.08; 95%CI: 1.04 - 1.13), no physical activity (PR = 1.06; 95%CI: 1.01 -
      1.11), and reasonable (PR = 1.07; 95%CI: 1.01 - 1.13) or poor access to health
      services (PR = 1.07; 95%CI: 1.02 - 1.12). CONCLUSIONS: The prevalence of MDE in
      this population was similar to that of the general Brazilian population. The
      association between MDE and poor access to health services indicates a missed
      opportunity for early diagnosis. Public measures against social and health
      inequalities are necessary to ensure equity in these communities.

PMID- 24870005
TI  - [How to reduce health inequities by targeting social determinants: the role of
      the health sector in Mexico].
AB  - OBJECTIVE: To study lines of action implemented in Mexico by the health sector
      from 2007 to 2012 in order to combat health inequities by targeting social
      determinants. To contribute to better understanding and knowledge of how health
      system inequalities in the Region of the Americas can be reduced. To formulate
      recommendations for designing a future public policy agenda to address the social
      determinants associated with health inequities in Mexico. METHODS: The policies
      and programs established in the National Health Program (PRONASA) 2007 - 2012
      were reviewed, and those that met four criteria were selected: i) they affected
      the social determinants of health (SDH); ii) they developed specific lines of
      action aimed at reducing health inequities; iii) they set concrete goals; and iv)
      they had been evaluated to determine whether those goals had been met. Three
      programs were selected: Seguro Popular, Programa de Desarrollo Humano
      Oportunidades (PDHO), and Caravanas de la Salud. Once each program's specific
      lines of action targeting SDH had been identified, the monitoring and evaluation
      indicators established in PRONASA 2007 - 2012, along with other available
      evaluations and empirical evidence, were used to measure the extent to which the
      goals were met. RESULTS: The findings showed that Seguro Popular had had a
      positive impact in terms of the financial protection of lower-income households.
      Moreover, the reduction in the gap between workers covered by the social security
      system and those who were not was more evident. By reducing poverty among its
      beneficiaries, the PDHO also managed to reduce health inequities. The indicators
      for Caravanas de la Salud, on the other hand, did not show statistically
      significant differences between the control localities and the localities covered
      by the program, except in the case of Pap tests. CONCLUSIONS: These findings have
      important public policy implications for designing an agenda that promotes
      continued targeting of SDH and heightening its impact in terms of reducing
      inequities. Guaranteeing the effective exercise of social rights, without
      socioeconomic, employment, ethnic, or gender-based exclusion, will be key. Action
      to provide comprehensive, inclusive, equitable, effective, and quality coverage,
      supported by a preventive and remedial model of primary health care, are
      recommended. Strategies should be centered on primary health services, because at
      that level, more comprehensive care focusing on the person rather than the
      disease can be provided. It will also be necessary to include periodic monitoring
      and evaluation phases to offer the comprehensive social protection system
      scientific armor and guarantee its effectiveness.

PMID- 24870006
TI  - [Tuberculosis and social inequity in health: an ecological study using
      multivariate statistical techniques, Sao Paulo, Brazil].
AB  - OBJECTIVE: To identify the patterns of Sao Paulo state municipalities, in Brazil,
      regarding the relationship between tuberculosis and indicators of health care
      services, health care service availability, context, and social inequality.
      METHODS: This ecological study covered all 645 municipalities of Sao Paulo and
      eight variables belonging to three dimensions: health care service availability,
      context, and social inequality. Data were analyzed using hierarchical and non
      hierarchical clustering, principal components analysis, and geoprocessing.
      RESULTS: The analysis revealed five groups of municipalities: group 1 (117
      municipalities), with similar directly observed treatment (DOT) and family health
      strategy (FHS) coverage, high tuberculosis incidence and death coefficients, and
      a low human development index (HDI); group 2 (142 municipalities), with low DOT
      and FHS coverage; group 3 (36 municipalities), with medium DOT and FHS coverage
      and high tuberculosis incidence, high demand for anti-HIV testing, and treatment
      dropout; group 4 (186 municipalities) with lower HDI as compared to groups 2, 3,
      and 5, but high FHS coverage and the lowest numbers of anti-HIV testing,
      tuberculosis incidence, and DOT coverage; and group 5 (164 municipalities), with
      better social conditions as compared to the other groups, medium FHS coverage,
      and higher DOT coverage. Together, the first two components selected for the
      study-health service availability in terms of DOT coverage indicator and social
      inequality indicator-explained 76.96% of the variance. In municipalities with
      high DOT coverage there was evidence of better organized tuberculosis control
      services. CONCLUSIONS: Municipalities with the highest social inequality had FHS
      coverage. However, without DOT, FHS seem less efficient to control tuberculosis.

PMID- 24870007
TI  - [What we know about men who commit violence against their intimate partners: a
      systematic review].
AB  - OBJECTIVE: To analyze the profile of men who commit violence against their female
      intimate partners. METHODS: A systematic review of the international literature
      published between 2000 and 2010 was conducted in the LILACS, MEDLINE, and SciELO
      databases. The search retrieved 3 452 articles, 33 of which were selected
      according to inclusion and exclusion criteria. The selected articles were
      analyzed for bibliometric data and socioeconomic characteristics of the men
      accused of committing violence against their partners. RESULTS: Most articles
      were published between 2000 and 2010, in English, based on data reported by the
      victims. Some variables were associated with domestic violence, such as
      educational attainment and employment status of the offender. These variables did
      not include the duration of the relationships. CONCLUSIONS: There is a
      significant gap in literature regarding the study of motivations and conditioning
      factors behind perpetrators of domestic violence. Investigating these factors is
      important in order to establish measures against this type of violence.

PMID- 24870008
TI  - [Health inequality among vulnerable groups in Mexico: older adults, indigenous
      people, and migrants].
AB  - Health vulnerability refers to a lack of protection for specific population
      groups with specific health problems, as well as the disadvantages they face in
      solving them in comparison with other population groups. This major public health
      problem has multiple and diverse causes, including a shortage of trained health
      care personnel and the lack of family, social, economic, and institutional
      support in obtaining care and minimizing health risks. Health vulnerability is a
      dynamic condition arising from the confluence of multiple social determinants.
      This article attempts to describe the health situation of three vulnerable groups
      in Mexico-older adults, indigenous people, and migrants-and, after defining the
      needs of each, explore measures that could contribute to the design and
      implementation of public health policies better tailored to their respective
      needs. 

PMID- 24870009
TI  - The other social capital: a needed look at Latin America.

PMID- 24870010
TI  - [Implicit value judgments in the measurement of health inequalities].
AB  - CONTEXT: Quantitative estimates of the magnitude, direction, and rate of change
      of health inequalities play a crucial role in creating and assessing policies
      aimed at eliminating the disproportionate burden of disease in disadvantaged
      populations. It is generally assumed that the measurement of health inequalities
      is a value-neutral process, providing objective data that are then interpreted
      using normative judgments about whether a particular distribution of health is
      just, fair, or socially acceptable. METHODS: We discuss five examples in which
      normative judgments play a role in the measurement process itself, through either
      the selection of one measurement strategy to the exclusion of others or the
      selection of the type, significance, or weight assigned to the variables being
      measured. FINDINGS: Overall, we find that many commonly used measures of
      inequality are value laden and that the normative judgments implicit in these
      measures have important consequences for interpreting and responding to health
      inequalities. CONCLUSIONS: Because values implicit in the generation of health
      inequality measures may lead to radically different interpretations of the same
      underlying data,we urge researchers to explicitly consider and transparently
      discuss the normative judgments underlying their measures. We also urge
      policymakers and other consumers of health inequalities data to pay close
      attention to the measures on which they base their assessments of current and
      future health policies.

PMID- 24870011
TI  - [Explaining racial disparities in infant health in Brazil].
AB  - OBJECTIVES: We sought to quantify how socioeconomic, health care, demographic,
      and geographic effects explain racial disparities in low birth weight (LBW) and
      preterm birth (PTB) rates in Brazil. METHODS: We employed a sample of 8 949
      infants born between 1995 and 2009 in 15 cities and 7 provinces in Brazil. We
      focused on disparities in LBW (< 2 500 g) and PTB (< 37 gestational weeks)
      prevalence between infants of African ancestry alone or African mixed with other
      ancestries, and European ancestry alone. We used a decomposition model to
      quantify the contributions of conceptually relevant factors to these disparities.
      RESULTS: The model explained 45% to 94% of LBW and 64% to 94% of PTB disparities
      between the African ancestry groups and European ancestry. Differences in
      prenatal care use and geographic location were the most important contributors,
      followed by socioeconomic differences. The model explained the majority of the
      disparities for mixed African ancestry and part of the disparity for African
      ancestry alone. CONCLUSIONS: Public policies to improve children's health should
      target prenatal care and geographic location differences to reduce health
      disparities between infants of African and European ancestries in Brazil.

PMID- 24870012
TI  - Strength in unity: the power of redesign to align the hospital team.
AB  - OBJECTIVE: The aim of Queen Elizabeth II Jubilee Hospital (QEII) redesign project
      (QEII United) was to enhance timely access to an inpatient bed and maximise
      opportunities to value add during the inpatient episode of care. METHODS: A
      tripartite relationship between the hospital team, system manager and external
      consultants. The team, QEII United, was formed to 'diagnose, solve and implement'
      change under the unifying metaphorical banner of a football team. A marketing
      strategy and communication plan targeted the key 'players' and outlined the 'game
      plan'. Baseline data were collected, analysed and reported in keeping with key
      aims. Strategies for systems improvement implementation were attached to key
      performance indicators (KPIs). RESULTS: Thematic KPIs were developed to embed
      internal process change to reflect the contributions made towards the National
      Emergency Access Target (NEAT) at each stage of the patient journey. As such,
      access block of under 20%, morning discharge rates of 50% before midday, reduced
      length of stay for selected elective orthopaedic and general medical diagnostic
      related groupings (DRGs; i.e. relative stay index <=1) and hospital in the home
      (HITH) utilisation rates 1.5% of all admissions were all met. Key to
      sustainability was the transfer of clinical redesign skills to hospital staff and
      the fostering of emergent ground up leadership. CONCLUSIONS: QEII United's
      success has been underpinned by the development of themed solution areas
      developed by the hospital staff themselves. Robust baseline data analysis used in
      combination with nationally available benchmarking data provided a quantitative
      starting point for the work. The collaborative elements of the program re
      energised the hospital team, who were kept informed by targeted communications,
      to establish quick wins and build trust and momentum for the more challenging
      areas.

PMID- 24870013
TI  - Denser fluids of charge-stabilized colloids form denser sediments.
AB  - Granular matter, where solid-like elasticity emerges in the absence of
      crystalline order, has been actively studied over the last few decades, targeting
      fundamental physical understanding of granular packings and glasses, abundant in
      everyday life and technology. We employ charge-stabilized sub-micron particles in
      a solvent, known as colloids, to form granular packings through a well-controlled
      process, where initially homogeneous and thermodynamically equilibrated colloidal
      fluids form solid sediments, when subjected to an effective gravity in a
      centrifuge. We demonstrate that particles' volume fraction phij in these
      sediments increases linearly with that in the initial fluid phi0, setting an
      upper limit phiRCP~ 0.64 on both phij and phi0, where phiRCP coincides with the
      well-known, yet highly controversial, 'random close packing' density of spheres,
      providing new insight into the physics of granular packings. The observed
      phij(phi0) dependence is similar to the one recently reported for colloidal hard
      spheres, sterically stabilized by surface-linked polymer combs (S. R. Liber, et
      al., Proc. Natl. Acad. Sci. U. S. A., 2013, 110, 5769-5773). However, the lower
      limit on sediment densities drops to phij~ 0.49 in the present work, suggesting
      that sedimented charge-stabilized silica are able to overcome mutual
      electrostatic repulsions, forming gel-like structures stabilized by occasional
      van der Waals contacts. Finally, by introducing particle size polydispersity,
      which significantly modifies fluid structure and sedimentation dynamics, we
      almost completely diminish the phij(phi0) dependence, bringing phij(0) close to
      its value in frictionless systems. 

PMID- 24870015
TI  - Covalent grafting of chitosan onto stainless steel through aryldiazonium self
      adhesive layers.
AB  - Although the conventional methods for strong attachment of chitosan onto
      stainless steel require many steps in different solvents, it has been
      demonstrated in this work that covalent grafting of chitosan on a steel surface
      can be easily achieved through the formation of a self-adhesive surface based on
      aryldiazonium seed layers. Initially, a polyaminophenyl layer is grafted on a
      stainless steel surface by means of the one-step GraftFast(TM) process (diazonium
      induced anchoring process). The grafted aminophenyl groups are then converted to
      an aryldiazonium seed layer by simply dipping the substrate in a sodium nitrite
      acidic solution. That diazonium-rich grafted layer can be used as a self-adhesive
      surface for subsequent spontaneous coating of chitosan onto the steel surface. X
      ray photoelectron and impedance electrochemical spectroscopies were used to
      characterize the pristine and modified steel samples. As evidenced from impedance
      and linear polarization results, the primary polyaminophenyl layer characterized
      by a high charge transfer resistance contributed to better protection against
      corrosion of the resulting chitosan-coated steel in sulfuric acid medium. 

PMID- 24870014
TI  - Effects of pitavastatin on the expression of VCAM-1 and its target gene miR-126
      in cultured human umbilical vein endothelial cells.
AB  - OBJECTIVES: Reducing the expression of endothelial cell adhesion molecules is
      conducive to the decrease of inflammation-induced vascular complications. In this
      study, we observed pitavastatin on expression of vascular cell adhesion molecule
      1 (VCAM-1) and its influence on VCAM-1's target gene miR-126 in endothelial
      cells. The purpose of this study is to explore the mechanism of pitavastatin in
      prevention and treatment of atherosclerosis. METHODS: HUVEC were cultured in
      M1640 and passages 2-5 were used in experiments. The cells were randomly divided
      into three groups, control, TNF-alpha and pitavastatin group. Cells of TNF-alpha
      group were co-incubated with different concentrations (10, 20, 30 MUg/L) of TNF
      alpha for 24 h. Cells of pitavastatin group were firstly coincubated with (0.01,
      0.1, 1 MUmol/L) pitavastatin, respectively, for 1 h, then coincubated with 30
      MUg/L TNF-alpha for 24 h. VCAM-1 and miR-126 mRNA were detected by RT-PCR, and
      Western blotting was used to detect protein expression of VCAM-1. RESULTS: Both
      detection methods have showed that TNF-alpha stimulation significantly increased
      the mRNA and protein expression of VCAM-1 in a dose-dependent manner, and miR-126
      mRNA expression exhibited a decreasing trend. The increase of VCAM-1 mRNA and
      protein expression induced by TNF-alpha was inhibited by pitavastatin in a dose
      dependent manner, too. However, there were no differences of the expression of
      miR-126 among three groups. CONCLUSIONS: These effects may explain the ability of
      pitavastatin to reduce the progression of atherosclerosis. The findings further
      suggest that inhibitory effect of pitavastatin on VCAM-1 is not related to miR
      126 but depends on other ways.

PMID- 24870017
TI  - High-throughput fluorescence-based screening assays for tryptophan-catabolizing
      enzymes.
AB  - Indoleamine 2,3-dioxygenase (IDO1) and tryptophan 2,3-dioxygenase (TDO) are two
      structurally different enzymes that have a different tissue distribution and
      physiological roles, but both catalyze the conversion of tryptophan to N
      formylkynurenine (NFK). IDO1 has been clinically validated as a small-molecule
      drug target for cancer, while preclinical studies indicate that TDO may be a
      target for cancer immunotherapy and neurodegenerative disease. We have developed
      a high-throughput screening assay for IDO1 and TDO based on a novel chemical
      probe, NFK Green, that reacts specifically with NFK to form a green fluorescent
      molecule with an excitation wavelength of 400 nm and an emission wavelength of
      510 nm. We provide the first side-by-side comparison of a number of published
      inhibitors of IDO1 and TDO and reveal that the preclinical IDO1 inhibitor
      Compound 5l shows significant cross-reactivity with TDO, while the relative
      selectivity of other published inhibitors was confirmed. The suitability for high
      throughput screening of the assays was demonstrated by screening a library of
      87,000 chemical substances in 384- or 1536-well format. Finally, we demonstrate
      that the assay can also be used to measure the capacity of cells to metabolize
      tryptophan and to measure the cellular potency of IDO1 and TDO inhibitors. 

PMID- 24870018
TI  - Monomer emission and aggregate emission of an imidazolium macrocycle based on
      bridged tetraphenylethylene and their quenching by C60.
AB  - A novel imidazolium macrocycle based on bridged tetraphenylethylene (TPE) was
      synthesized. Because it bears the bridged TPE units, this macrocycle not only
      displays an aggregation-induced emission (AIE) effect but also exhibits monomer
      emission, which is very rare in AIE compounds. With aggregation of the
      macrocycle, the aggregate emission increases while the monomer emission
      decreases. It was found that this imidazolium macrocycle can form a stable 2:1
      complex with C60, which gives rise to quenching of both the aggregate emission
      and the monomer emission. Unexpectedly, the aggregate emission exhibited a higher
      quenching efficiency than the monomer emission, probably because one adsorbed C60
      molecule could affect more macrocycle molecules in the aggregate. 

PMID- 24870016
TI  - Ultra-High-Throughput Screening of Natural Product Extracts to Identify
      Proapoptotic Inhibitors of Bcl-2 Family Proteins.
AB  - Antiapoptotic Bcl-2 family proteins are validated cancer targets composed of six
      related proteins. From a drug discovery perspective, these are challenging
      targets that exert their cellular functions through protein-protein interactions
      (PPIs). Although several isoform-selective inhibitors have been developed using
      structure-based design or high-throughput screening (HTS) of synthetic chemical
      libraries, no large-scale screen of natural product collections has been
      reported. A competitive displacement fluorescence polarization (FP) screen of
      nearly 150,000 natural product extracts was conducted against all six
      antiapoptotic Bcl-2 family proteins using fluorochrome-conjugated peptide ligands
      that mimic functionally relevant PPIs. The screens were conducted in 1536-well
      format and displayed satisfactory overall HTS statistics, with Z'-factor values
      ranging from 0.72 to 0.83 and a hit confirmation rate between 16% and 64%.
      Confirmed active extracts were orthogonally tested in a luminescent assay for
      caspase-3/7 activation in tumor cells. Active extracts were resupplied, and
      effort toward the isolation of pure active components was initiated through
      iterative bioassay-guided fractionation. Several previously described altertoxins
      were isolated from a microbial source, and the pure compounds demonstrate
      activity in both Bcl-2 FP and caspase cellular assays. The studies demonstrate
      the feasibility of ultra-high-throughput screening using natural product sources
      and highlight some of the challenges associated with this approach. 

PMID- 24870019
TI  - Warning! fire in the ICU.
AB  - At 5:30 pm on December 17, 2010, shortly after a power failure, smoke filled the
      Intensive Care Unit (ICU) of Federico II University Hospital in Naples, Italy,
      triggering the hospital emergency alarm system. Immediately, staff began
      emergency procedures and alerted rescue teams. All patients were transferred
      without harm. The smoke caused pharyngeal and conjunctival irritation in some
      staff members. After a brief investigation, firefighters discovered the cause of
      the fire was a failure of the Uninterruptible Power Supply (UPS).

PMID- 24870020
TI  - U.S. refinery efficiency: impacts analysis and implications for fuel carbon
      policy implementation.
AB  - In the next two decades, the U.S. refining industry will face significant changes
      resulting from a rapidly evolving domestic petroleum energy landscape. The rapid
      influx of domestically sourced tight light oil and relative demand shifts for
      gasoline and diesel will impose challenges on the ability of the U.S. refining
      industry to satisfy both demand and quality requirements. This study uses results
      from Linear Programming (LP) modeling data to examine the potential impacts of
      these changes on refinery, process unit, and product-specific efficiencies,
      focusing on current baseline efficiency values across 43 existing large U.S.
      refineries that are operating today. These results suggest that refinery and
      product-specific efficiency values are sensitive to crude quality, seasonal and
      regional factors, and refinery configuration and complexity, which are determined
      by final fuel specification requirements. Additional processing of domestically
      sourced tight light oil could marginally increase refinery efficiency, but these
      benefits could be offset by crude rebalancing. The dynamic relationship between
      efficiency and key parameters such as crude API gravity, sulfur content, heavy
      products, residual upgrading, and complexity are key to understanding possible
      future changes in refinery efficiency. Relative to gasoline, the efficiency of
      diesel production is highly variable, and is influenced by the number and
      severity of units required to produce diesel. To respond to future demand
      requirements, refiners will need to reduce the gasoline/diesel (G/D) production
      ratio, which will likely result in greater volumes of diesel being produced
      through less efficient pathways resulting in reduced efficiency, particularly on
      the marginal barrel of diesel. This decline in diesel efficiency could be offset
      by blending of Gas to Liquids (GTL) diesel, which could allow refiners to uplift
      intermediate fuel streams into more efficient diesel production pathways, thereby
      allowing for the efficient production of incremental barrels of diesel without
      added capital investment for the refiner. Given the current wide range of
      refinery carbon intensity values of baseline transportation fuels in LCA models,
      this study has shown that the determination of refinery, unit, and product
      efficiency values requires careful consideration in the context of specific
      transportation fuel GHG policy objectives. 

PMID- 24870021
TI  - How to find a leucine in a haystack? Structure, ligand recognition and regulation
      of leucine-aspartic acid (LD) motifs.
AB  - LD motifs (leucine-aspartic acid motifs) are short helical protein-protein
      interaction motifs that have emerged as key players in connecting cell adhesion
      with cell motility and survival. LD motifs are required for embryogenesis, wound
      healing and the evolution of multicellularity. LD motifs also play roles in
      disease, such as in cancer metastasis or viral infection. First described in the
      paxillin family of scaffolding proteins, LD motifs and similar acidic LXXLL
      interaction motifs have been discovered in several other proteins, whereas 16
      proteins have been reported to contain LDBDs (LD motif-binding domains).
      Collectively, structural and functional analyses have revealed a surprising
      multivalency in LD motif interactions and a wide diversity in LDBD architectures.
      In the present review, we summarize the molecular basis for function, regulation
      and selectivity of LD motif interactions that has emerged from more than a decade
      of research. This overview highlights the intricate multi-level regulation and
      the inherently noisy and heterogeneous nature of signalling through short protein
      protein interaction motifs.

PMID- 24870022
TI  - Exploring the roles of PALB2 at the crossroads of DNA repair and cancer.
AB  - PALB2 [partner and localizer of BRCA2 (breast cancer early-onset 2)] [corrected]
      has emerged as a key player in the maintenance of genome integrity. Biallelic
      mutations in PALB2 cause FA (Fanconi's anaemia) subtype FA-N, a devastating
      inherited disorder marked by developmental abnormalities, bone marrow failure and
      childhood cancer susceptibility, whereas monoallelic mutations predispose to
      breast, ovarian and pancreatic cancer. The tumour suppressor role of PALB2 has
      been intimately linked to its ability to promote HR (homologous recombination)
      mediated repair of DNA double-strand breaks. Because PALB2 lies at the crossroads
      between FA, HR and cancer susceptibility, understanding its function has become
      the primary focus of several studies. The present review discusses a current
      synthesis of the contribution of PALB2 to these pathways. We also provide a
      molecular description of FA- or cancer-associated PALB2 mutations.

PMID- 24870025
TI  - Switching on ubiquitylation by phosphorylating a ubiquitous activator.
AB  - The dysfunction of the E3 ubiquitin ligase Parkin is a key contributor to the
      development of early-onset Parkinson's disease. Parkin is responsible for the
      labelling of outer mitochondrial membrane proteins with the small modifier
      protein ubiquitin in response to oxidative stress. This ubiquitylation signals
      the clearance of the damaged mitochondria to preserve overall cell health. Recent
      structural and biochemical experiments have shown that native Parkin exists in an
      autoinhibited state that must be activated in order to unmask its full
      ubiquitylation potential. In a recent article in the Biochemical Journal (vol.
      460, pp. 127-139), Kazlauskaite and co-workers identified that the Parkinson's
      disease-associated kinase PINK1 [PTEN (phosphatase and tensin homologue deleted
      on chromosome 10)-induced putative kinase 1] can phosphorylate ubiquitin in
      response to mitochondrial depolarization. Furthermore, the authors demonstrated
      that phosphorylated ubiquitin can activate Parkin's E3 ligase activity and
      promote both increased autoubiquitylation and substrate ubiquitylation of the
      mitochondrial protein Miro1. The study provides exciting initial insights that
      show how PINK1 might activate ubiquitin through phosphorylation, and how this
      important regulatory step might switch on Parkin-mediated ubiquitylation.

PMID- 24870026
TI  - Exploiting level anti-crossings (LACs) in the rotating frame for transferring
      spin hyperpolarization.
AB  - A method of transferring hyperpolarization among scalar-coupled nuclear spins is
      proposed, which is based on spin mixing at energy Level Anti-Crossing (LAC)
      regions. To fulfill LAC conditions a resonant RF-field was applied with properly
      set frequency and amplitude. In this situation LACs occur between the nuclear
      spin levels in the rotating doubly tilted reference frame. The validity of the
      approach is demonstrated by taking as an example the transfer of para-hydrogen
      induced polarization in a symmetric molecule, whose coupled spin network can be
      modeled as a four-spin AA'MM'-system with two pairs of 'isochronous' spins. For
      this spin system LAC positions have been identified; rules for the sign of spin
      polarization have been established. The dependence of the polarization transfer
      efficiency on the RF-field parameters and on the time profile of switching off
      the RF-field has been studied in detail; experimental results are in excellent
      agreement with the theory developed. In general, exploiting LACs in the rotating
      doubly tilted frame is a powerful tool for manipulating hyperpolarization in
      multispin systems. 

PMID- 24870023
TI  - Kinetic characterization of human butyrylcholinesterase mutants for the
      hydrolysis of cocaethylene.
AB  - It is known that the majority of cocaine users also consume alcohol. Alcohol can
      react with cocaine to produce a significantly more cytotoxic compound,
      cocaethylene. Hence a truly valuable cocaine-metabolizing enzyme as treatment for
      cocaine abuse/overdose should be efficient for not only cocaine itself, but also
      cocaethylene. The catalytic parameters (kcat and KM) of human BChE
      (butyrylcholinesterase) and two mutants (known as cocaine hydrolases E14-3 and
      E12-7) for cocaethylene are characterized in the present study, for the first
      time, in comparison with those for cocaine. On the basis of the obtained kinetic
      data, wild-type human BChE has a lower catalytic activity for cocaethylene
      (kcat=3.3 min(-1), KM=7.5 MUM and kcat/KM=4.40 * 10(5) M(-1).min(-1)) compared
      with its catalytic activity for (-)-cocaine. E14-3 and E12-7 have a considerably
      improved catalytic activity against cocaethylene compared with the wild-type
      BChE. E12-7 is identified as the most efficient enzyme for hydrolysing
      cocaethylene in addition to its high activity for (-)-cocaine. E12-7 has an 861
      fold improved catalytic efficiency for cocaethylene (kcat=3600 min(-1), KM=9.5
      MUM and kcat/KM=3.79 * 10(8) M(-1).min(-1)). It has been demonstrated that E12-7
      as an exogenous enzyme can indeed rapidly metabolize cocaethylene in rats.
      Further kinetic modelling has suggested that E12-7 with an identical
      concentration as that of the endogenous BChE in human plasma can effectively
      eliminate (-)-cocaine, cocaethylene and norcocaine in simplified kinetic models
      of cocaine abuse and overdose associated with the concurrent use of cocaine and
      alcohol.

PMID- 24870027
TI  - Comprehensive study of ultrafast excited-state proton transfer in water and D2O
      providing the missing RO(-)...H(+) ion-pair fingerprint.
AB  - Steady-state and time-resolved optical techniques were employed to study the
      photoprotolytic mechanism of a general photoacid. Previously, a general scheme
      was suggested that includes an intermediate product that, up until now, had not
      been clearly observed experimentally. For our study, we used quinone cyanine 7
      (QCy7) and QCy9, the strongest photoacids synthesized so far, to look for the
      missing intermediate product of an excited-state proton transfer to the solvent.
      Low-temperature steady-state emission spectra of both QCy7 and QCy9 clearly show
      an emission band at T < 165 K in H2O ice that could be assigned to ion-pair RO(
      )*...H3O(+), the missing intermediate. Room-temperature femtosecond pump-probe
      spectroscopy transient spectra at short times (t < 4 ps) also shows the existence
      of transient absorption and emission bands that we assigned to the RO(
      )*...H3O(+) ion pair. The intermediate dissociates on a time scale of 1 ps and
      about 1.5 ps in H2O and D2O samples, respectively. 

PMID- 24870028
TI  - Childhood adversity, midlife generativity, and later life well-being.
AB  - OBJECTIVES: Prior studies confirm that after experiencing childhood adversity,
      resilient adults can recover and engage in generative growth. This study explored
      the long-term effects of childhood adversity (assessed as harsh parenting and/or
      childhood poverty) on successful aging for individuals who either achieved or
      failed to achieve Erikson's psychosocial developmental stage of generativity in
      midlife. METHOD: The study utilized a sample of 636 men from the Harvard Sample
      and Inner City Cohort of the 73-year longitudinal Study of Adult Development.
      Nested ordinary least squares regression models were used to test the mediating
      and moderating effects of midlife generativity on later life health and
      adjustment to aging. RESULTS: Men who experienced childhood adversity were less
      likely than men with no childhood adversity to achieve generativity in midlife.
      Although achievement of generativity was associated with better later life health
      and adjustment to aging, it neither mediated nor moderated the negative relation
      between childhood poverty and later life health outcomes. However, for men who
      experienced an adversarial childhood, achievement of generativity mediated and
      moderated adjustment to aging. DISCUSSION: Results suggest that psychosocial
      growth in adulthood can compensate for the long-term negative effects of an
      adversarial childhood on adjustment to aging, but not for later life health.

PMID- 24870029
TI  - Age Differences in Reactions to Social Rejection: The Role of Cognitive Resources
      and Appraisals.
AB  - OBJECTIVES: Social rejection is a negative social experience individuals of all
      ages may encounter in everyday life. It is unclear whether social rejection
      affects older adults more or less than younger adults. This study investigated
      age differences in reactions following a direct rejection and the moderating
      effects of cognitive resources and appraisals. METHOD: Eighty-three younger (18
      26 years) and 53 older (60-86 years) adults engaged in an online interview during
      which they were either accepted or rejected seemingly by another participant. We
      examined participants' self-reported mood before and after the interview as well
      as verbal self-complexity. RESULTS: Older adults reported greater increases in
      hurt feelings following rejection than younger adults. The age difference was
      further moderated by cognitive resources and appraisals. Among older rejected
      adults, those who were poorer in processing speed and those who appraised the
      rejection more negatively felt more hurt feelings. Older rejected adults were
      also rated lower in self-complexity than older accepted adults, whereas younger
      rejected adults and accepted adults did not differ. DISCUSSION: The findings are
      largely consistent with life-span developmental theories and highlight the
      importance of cognitive processes when examining age differences in experiencing
      social rejection.

PMID- 24870030
TI  - Make Mine Home: Spatial Modification With Physical and Social Implications in
      Older Adulthood.
AB  - OBJECTIVE: The process of moving in older adulthood, intertwined with loss and
      anticipation, is grounded in material commodities that include one's residence
      and its contents. This article emphasizes the role of material culture in housing
      transitions. METHODS: Based on an ethnographic study (January 2009-May 2012) of
      older Americans (n = 81) relocating, this study utilized interviews, participant
      observation, and review of documents. RESULTS: Personalization is both a
      reflection of a previous self as a homeowner and a projection of a future self as
      extensions of temporality intertwine with commodification processes. Through
      creative appropriations of their housing, residences are personalized to promote
      physical or social functionality or because of preference. DISCUSSION: Given the
      findings, the transitions involved in relocation must be supported by greater
      understanding and facilitation of key issues of personalization and its
      importance to older adults' decisions to relocate.

PMID- 24870031
TI  - Aflatoxins of type B and G affect porcine dendritic cell maturation in vitro.
AB  - The toxic effects of highly carcinogenic mycotoxins, especially aflatoxins (AF),
      on key antigen-presenting cells, such as dendritic cells (DC), are largely
      unknown. To elucidate the effect of AF on DC function, porcine monocyte-derived
      DC (MoDC) were treated with a mixture of several AF (i.e., AFB1, AFB2, AFG1, and
      AFG2) and the phagocytic capacity, the membrane expression level of several DC
      activation markers, the T-cell proliferation-inducing capacity, and the cytokine
      secretion pattern were assessed. As compared to untreated MoDC, AF significantly
      up-regulated the expression of the co-stimulatory molecules CD25 and CD80/86.
      However, the phagocytic activity of MoDC was not affected by AF treatment. While
      the cytokine secretion pattern of AF-treated MoDC was similar to control MoDC,
      the T-cell proliferation-inducing capacity of MoDC was increased upon aflatoxin
      treatment. The results indicate that a mixture of naturally occurring AF enhances
      the antigen-presenting capacity of DC, which could explain the observed
      immunotoxicity of AF by breaking down tolerance and further emphasizes the need
      to reduce the admissible level of AF in agricultural commodities.

PMID- 24870032
TI  - Role of TGF-beta receptor III localization in polarity and breast cancer
      progression.
AB  - The majority of breast cancers originate from the highly polarized luminal
      epithelial cells lining the breast ducts. However, cell polarity is often lost
      during breast cancer progression. The type III transforming growth factor-beta
      cell surface receptor (TbetaRIII) functions as a suppressor of breast cancer
      progression and also regulates the process of epithelial-to-mesenchymal
      transition (EMT), a consequence of which is the loss of cell polarity. Many cell
      surface proteins exhibit polarized expression, being targeted specifically to the
      apical or basolateral domains. Here we demonstrate that TbetaRIII is
      basolaterally localized in polarized breast epithelial cells and that disruption
      of the basolateral targeting of TbetaRIII through a single amino acid mutation of
      proline 826 in the cytosolic domain results in global loss of cell polarity
      through enhanced EMT. In addition, the mistargeting of TbetaRIII results in
      enhanced proliferation, migration, and invasion in vitro and enhanced tumor
      formation and invasion in an in vivo mouse model of breast carcinoma. These
      results suggest that proper localization of TbetaRIII is critical for maintenance
      of epithelial cell polarity and phenotype and expand the mechanisms by which
      TbetaRIII prevents breast cancer initiation and progression. 

PMID- 24870033
TI  - FHIP and FTS proteins are critical for dynein-mediated transport of early
      endosomes in Aspergillus.
AB  - The minus end-directed microtubule motor cytoplasmic dynein transports various
      cellular cargoes, including early endosomes, but how dynein binds to its cargo
      remains unclear. Recently fungal Hook homologues were found to link dynein to
      early endosomes for their transport. Here we identified FhipA in Aspergillus
      nidulans as a key player for HookA (A. nidulans Hook) function via a genome-wide
      screen for mutants defective in early-endosome distribution. The human homologue
      of FhipA, FHIP, is a protein in the previously discovered FTS/Hook/FHIP (FHF)
      complex, which contains, besides FHIP and Hook proteins, Fused Toes (FTS).
      Although this complex was not previously shown to be involved in dynein-mediated
      transport, we show here that loss of either FhipA or FtsA (A. nidulans FTS
      homologue) disrupts HookA-early endosome association and inhibits early endosome
      movement. Both FhipA and FtsA associate with early endosomes, and interestingly,
      while FtsA-early endosome association requires FhipA and HookA, FhipA-early
      endosome association is independent of HookA and FtsA. Thus FhipA is more
      directly linked to early endosomes than HookA and FtsA. However, in the absence
      of HookA or FtsA, FhipA protein level is significantly reduced. Our results
      indicate that all three proteins in the FtsA/HookA/FhipA complex are important
      for dynein-mediated early endosome movement. 

PMID- 24870035
TI  - Fatigue assessment and its impact in the quality of life of patients with
      ankylosing spondylitis.
AB  - The most frequently reported symptoms by patients with ankylosing spondylitis
      (AS) are pain, stiffness, and fatigue. Previous studies have estimated a 63%
      prevalence of fatigue in AS, with a low correlation of fatigue with pain and
      functional capacity. The objective of this study is to assess fatigue prevalence
      in AS patients and establish the main associated factors. A case-control study
      including AS patients according to New York modified criteria was carried out.
      The control group included individuals of the general population without
      rheumatic conditions, matched by gender, age, and socioeconomic level. Disease
      related variables were recorded. Functional capacity, disease activity, and
      quality of life were assessed using Bath Ankylosing Spondylitis Funcional Index
      (BASFI), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and
      ankylosing spondylitis quality of life (ASQoL). CES-D questionnaire was used to
      evaluate depression and fatigue severity scale (FSS) to evaluate fatigue. Sixty
      four consecutive AS patients and 95 controls were included. Patients' median age
      was 44 years (interquartile range (IQR), 33.25-53), 89.1% were male, and had a
      median disease duration of 17 years (IQR, 10.3-25). Fatigue prevalence in AS was
      73.4% compared to 30.5% in the control group (p < 0.001; OR, 2.08 (95% CI, 1.53
      2.83)). Furthermore, fatigue in AS correlated with ASQoL (r = 0.65), BASFI (r =
      0.52), BASDAI (r = 0.52), and depression (r = 0.51), whereas no correlation with
      age or disease duration was found. In the linear regression analysis using
      fatigue as the dependent variable, depression was the only associated variable (p
      = 0.01). No association with age, gender, disease duration, BASDAI, BASFI, or
      presence of comorbidities was found. Finally, BASDAI fatigue question correlated
      with the FSS (r = 0.55). Fatigue was significantly more prevalent in AS than in
      healthy controls. The main determinant factor of fatigue was the presence of
      depression, explaining 30% of its variability. Recognizing these factors could
      have important therapeutic implications.

PMID- 24870036
TI  - Does osteophytosis at the knee predict health-related quality of life decline? A
      3-year follow-up of the ROAD study.
AB  - The objective of the present longitudinal study was to clarify whether
      osteophytosis and joint space narrowing predict quality of life (QOL) decline
      using a longitudinal population-based cohort of the Research on
      Osteoarthritis/osteoporosis Against Disability (ROAD) study. The present study
      analyzed 1,525 participants who completed the radiographic examination at
      baseline and questionnaires regarding QOL at a 3-year follow-up (546 men and 979
      women; mean age, 67.0 +/- 11.0 years). This study examined the associations of
      osteophyte area (OPA) and minimum joint space width (mJSW) in the medial
      compartment of the knee at baseline with pain and physical functional disability
      measured by the Western Ontario and McMaster Universities Osteoarthritis Index
      (WOMAC). OPA and mJSW in the medial compartment of the knee were measured using a
      knee osteoarthritis (OA) computer-aided diagnosis system. Overall, OPA
      independently predicted physical functional disability after 3 years of follow
      up. When analyzed in men and women separately, OPA, rather than mJSW, was an
      independent predictor for pain and physical functional disability after 3 years
      of follow-up in men. OPA, rather than mJSW, also predicted worsening of pain in
      men during the 3-year follow-up, whereas in women, mJSW, rather than OPA,
      predicted worsening of pain. In conclusion, the present longitudinal study using
      a large-scale population from the ROAD study found gender differences in the
      association of osteophytosis and joint space narrowing with pain and physical
      functional disability.

PMID- 24870037
TI  - Nymphalid eyespot serial homologues originate as a few individualized modules.
AB  - Serial homologues are repeated traits that share similar development but occur in
      different parts of the body. Variation in number of repeats accounts for
      substantial diversity in animal form and considerable work has focused on
      identifying the factors accounting for this variation. Little is known, however,
      about how serial homologues originally become repeated, or about the relative
      timing of repeat individuation relative to repeat origin. Here, we show that the
      serially repeated eyespots on nymphalid butterfly wings most likely arose as a
      small cluster of units on the ventral hindwing that were later co-opted to the
      dorsal and anterior wing surfaces. Based on comparative analyses of over 400
      species, we found support for a model of eyespot origin followed by redeployment,
      rather than by the conventional model, where eyespots arose as a complete row of
      undifferentiated units that later gained individuation. In addition, eyespots
      most likely evolved from simpler pattern elements, single-coloured spots, which
      were already individuated among different wing sectors. Finally, the late
      appearance of eyespots on the dorsal, hidden wing surface further suggests that
      these novel complex traits originally evolved for one function (thwarting
      predator attacks) and acquired a second function (sexual signalling) when moved
      to a different body location. This broad comparative analysis illustrates how
      serial homologues may initially evolve as a few units serving a particular
      function and subsequently become repeated in novel body locations with new
      functions. 

PMID- 24870034
TI  - Genome-wide analysis of Saccharomyces cerevisiae identifies cellular processes
      affecting intracellular aggregation of Alzheimer's amyloid-beta42: importance of
      lipid homeostasis.
AB  - Amyloid-beta (Abeta)-containing plaques are a major neuropathological feature of
      Alzheimer's disease (AD). The two major isoforms of Abeta peptide associated with
      AD are Abeta40 and Abeta42, of which the latter is highly prone to aggregation.
      Increased presence and aggregation of intracellular Abeta42 peptides is an early
      event in AD progression. Improved understanding of cellular processes affecting
      Abeta42 aggregation may have implications for development of therapeutic
      strategies. Abeta42 fused to green fluorescent protein (Abeta42-GFP) was
      expressed in ~4600 mutants of a Saccharomyces cerevisiae genome-wide deletion
      library to identify proteins and cellular processes affecting intracellular
      Abeta42 aggregation by assessing the fluorescence of Abeta42-GFP. This screening
      identified 110 mutants exhibiting intense Abeta42-GFP-associated fluorescence.
      Four major cellular processes were overrepresented in the data set, including
      phospholipid homeostasis. Disruption of phosphatidylcholine, phosphatidylserine,
      and/or phosphatidylethanolamine metabolism had a major effect on intracellular
      Abeta42 aggregation and localization. Confocal microscopy indicated that Abeta42
      GFP localization in the phospholipid mutants was juxtaposed to the nucleus, most
      likely associated with the endoplasmic reticulum (ER)/ER membrane. These data
      provide a genome-wide indication of cellular processes that affect intracellular
      Abeta42-GFP aggregation and may have important implications for understanding
      cellular mechanisms affecting intracellular Abeta42 aggregation and AD disease
      progression. 

PMID- 24870038
TI  - Chimaeric load among sympatric social bacteria increases with genotype richness.
AB  - The total productivity of social groups can be determined by interactions among
      their constituents. Chimaeric load--the reduction of group productivity caused by
      antagonistic within-group heterogeneity--may be common in heterogeneous microbial
      groups due to dysfunctional behavioural interactions between distinct
      individuals. However, some instances of chimaerism in social microbes can
      increase group productivity, thus making a general relationship between
      chimaerism and group-level performance non-obvious. Using genetically similar
      strains of the soil bacterium Myxococcus xanthus that were isolated from a single
      centimetre-scale patch of soil, we tested for a relationship between degree of
      chimaerism (genotype richness) and total group performance at social behaviours
      displayed by this species. Within-group genotype richness was found to correlate
      negatively with total group performance at most traits examined, including
      swarming in both predatory and prey-free environments and spore production during
      development. These results suggest that interactions between such neighbouring
      strains in the wild will tend to be mutually antagonistic. Negative correlations
      between group performance and average genetic distance among group constituents
      at three known social genes were not found, suggesting that divergence at other
      loci that govern social interaction phenotypes is responsible for the observed
      chimaeric load. The potential for chimaeric load to result from co-aggregation
      among even closely related neighbours may promote the maintenance and
      strengthening of kin discrimination mechanisms, such as colony-merger
      incompatibilities observed in M. xanthus. The findings reported here may thus
      have implications for understanding the evolution and maintenance of diversity in
      structured populations of soil microbes.

PMID- 24870039
TI  - Zebra finches are sensitive to prosodic features of human speech.
AB  - Variation in pitch, amplitude and rhythm adds crucial paralinguistic information
      to human speech. Such prosodic cues can reveal information about the meaning or
      emphasis of a sentence or the emotional state of the speaker. To examine the
      hypothesis that sensitivity to prosodic cues is language independent and not
      human specific, we tested prosody perception in a controlled experiment with
      zebra finches. Using a go/no-go procedure, subjects were trained to discriminate
      between speech syllables arranged in XYXY patterns with prosodic stress on the
      first syllable and XXYY patterns with prosodic stress on the final syllable. To
      systematically determine the salience of the various prosodic cues (pitch,
      duration and amplitude) to the zebra finches, they were subjected to five tests
      with different combinations of these cues. The zebra finches generalized the
      prosodic pattern to sequences that consisted of new syllables and used prosodic
      features over structural ones to discriminate between stimuli. This strong
      sensitivity to the prosodic pattern was maintained when only a single prosodic
      cue was available. The change in pitch was treated as more salient than changes
      in the other prosodic features. These results show that zebra finches are
      sensitive to the same prosodic cues known to affect human speech perception. 

PMID- 24870041
TI  - Social learning in cooperative dilemmas.
AB  - Helping is a cornerstone of social organization and commonplace in human
      societies. A major challenge for the evolutionary sciences is to explain how
      cooperation is maintained in large populations with high levels of migration,
      conditions under which cooperators can be exploited by selfish individuals.
      Cultural group selection models posit that such large-scale cooperation evolves
      via selection acting on populations among which behavioural variation is
      maintained by the cultural transmission of cooperative norms. These models assume
      that individuals acquire cooperative strategies via social learning. This
      assumption remains empirically untested. Here, I test this by investigating
      whether individuals employ conformist or payoff-biased learning in public goods
      games conducted in 14 villages of a forager-horticulturist society, the Pahari
      Korwa of India. Individuals did not show a clear tendency to conform or to be
      payoff-biased and are highly variable in their use of social learning. This
      variation is partly explained by both individual and village characteristics. The
      tendency to conform decreases and to be payoff-biased increases as the value of
      the modal contribution increases. These findings suggest that the use of social
      learning in cooperative dilemmas is contingent on individuals' circumstances and
      environments, and question the existence of stably transmitted cultural norms of
      cooperation. 

PMID- 24870040
TI  - The effect of epistasis on sexually antagonistic genetic variation.
AB  - There is increasing evidence of segregating sexually antagonistic (SA) genetic
      variation for fitness in laboratory and wild populations, yet the conditions for
      the maintenance of such variation can be restrictive. Epistatic interactions
      between genes can contribute to the maintenance of genetic variance in fitness
      and we suggest that epistasis between SA genes should be pervasive. Here, we
      explore its effect on SA genetic variation in fitness using a two locus model
      with negative epistasis. Our results demonstrate that epistasis often increases
      the parameter space showing polymorphism for SA loci. This is because selection
      in one locus is affected by allele frequencies at the other, which can act to
      balance net selection in males and females. Increased linkage between SA loci had
      more marginal effects. We also show that under some conditions, large portions of
      the parameter space evolve to a state where male benefit alleles are fixed at one
      locus and female benefit alleles at the other. This novel effect of epistasis on
      SA loci, which we term the 'equity effect', may have important effects on
      population differentiation and may contribute to speciation. More generally,
      these results support the suggestion that epistasis contributes to population
      divergence. 

PMID- 24870042
TI  - Host ecotype generates evolutionary and epidemiological divergence across a
      pathogen metapopulation.
AB  - The extent and speed at which pathogens adapt to host resistance varies
      considerably. This presents a challenge for predicting when--and where--pathogen
      evolution may occur. While gene flow and spatially heterogeneous environments are
      recognized to be critical for the evolutionary potential of pathogen populations,
      we lack an understanding of how the two jointly shape coevolutionary trajectories
      between hosts and pathogens. The rust pathogen Melampsora lini infects two
      ecotypes of its host plant Linum marginale that occur in close proximity yet in
      distinct populations and habitats. In this study, we found that within-population
      epidemics were different between the two habitats. We then tested for pathogen
      local adaptation at host population and ecotype level in a reciprocal inoculation
      study. Even after controlling for the effect of spatial structure on infection
      outcome, we found strong evidence of pathogen adaptation at the host ecotype
      level. Moreover, sequence analysis of two pathogen infectivity loci revealed
      strong genetic differentiation by host ecotype but not by distance. Hence,
      environmental variation can be a key determinant of pathogen population genetic
      structure and coevolutionary dynamics and can generate strong asymmetry in
      infection risks through space.

PMID- 24870043
TI  - Macroecological and macroevolutionary patterns of leaf herbivory across vascular
      plants.
AB  - The consumption of plants by animals underlies important evolutionary and
      ecological processes in nature. Arthropod herbivory evolved approximately 415 Ma
      and the ensuing coevolution between plants and herbivores is credited with
      generating much of the macroscopic diversity on the Earth. In contemporary
      ecosystems, herbivory provides the major conduit of energy from primary producers
      to consumers. Here, we show that when averaged across all major lineages of
      vascular plants, herbivores consume 5.3% of the leaf tissue produced annually by
      plants, whereas previous estimates are up to 3.8* higher. This result suggests
      that for many plant species, leaf herbivory may play a smaller role in energy and
      nutrient flow than currently thought. Comparative analyses of a diverse global
      sample of 1058 species across 2085 populations reveal that models of stabilizing
      selection best describe rates of leaf consumption, and that rates vary
      substantially within and among major plant lineages. A key determinant of this
      variation is plant growth form, where woody plant species experience 64% higher
      leaf herbivory than non-woody plants. Higher leaf herbivory in woody species
      supports a key prediction of the plant apparency theory. Our study provides
      insight into how a long history of coevolution has shaped the ecological and
      evolutionary relationships between plants and herbivores. 

PMID- 24870044
TI  - Low ecological disparity in Early Cretaceous birds.
AB  - Ecological divergence is thought to be coupled with evolutionary radiations, yet
      the strength of this coupling is unclear. When birds diversified ecologically has
      received much less attention than their hotly debated crown divergence time.
      Here, we quantify how accurately skeletal morphology can predict ecology in
      living and extinct birds, and show that the earliest known assemblage of birds
      (=pygostylians) from the Jehol Biota (~125 Ma) was substantially impoverished
      ecologically. The Jehol avifauna has few representatives of highly preservable
      ecomorphs (e.g. aquatic forms) and a notable lack of ecomorphological overlap
      with the pterosaur assemblage (e.g. no large or aerially foraging pygostylians).
      Comparisons of the Jehol functional diversity with modern and subfossil avian
      assemblages show that taphonomic bias alone cannot explain the ecomorphological
      impoverishment. However, evolutionary simulations suggest that the constrained
      ecological diversity of the Early Cretaceous pygostylians is consistent with what
      is expected from a relatively young radiation. Regardless of the proximate
      biological explanation, the anomalously low functional diversity of the Jehol
      birds is evidence both for ecological vacancies in Cretaceous ecosystems, which
      were subsequently filled by the radiation of crown Aves, and for discordance
      between taxonomic richness and ecological diversity in the best-known Mesozoic
      ecosystem.

PMID- 24870045
TI  - Transitions in social complexity along elevational gradients reveal a combined
      impact of season length and development time on social evolution.
AB  - Eusociality is taxonomically rare, yet associated with great ecological success.
      Surprisingly, studies of environmental conditions favouring eusociality are often
      contradictory. Harsh conditions associated with increasing altitude and latitude
      seem to favour increased sociality in bumblebees and ants, but the reverse
      pattern is found in halictid bees and polistine wasps. Here, we compare the life
      histories and distributions of populations of 176 species of Hymenoptera from the
      Swiss Alps. We show that differences in altitudinal distributions and development
      times among social forms can explain these contrasting patterns: highly social
      taxa develop more quickly than intermediate social taxa, and are thus able to
      complete the reproductive cycle in shorter seasons at higher elevations. This
      dual impact of altitude and development time on sociality illustrates that
      ecological constraints can elicit dynamic shifts in behaviour, and helps explain
      the complex distribution of sociality across ecological gradients. 

PMID- 24870046
TI  - A desert ant's memory of recent visual experience and the control of route
      guidance.
AB  - Insects such as desert ants learn stereotyped visual routes between their nests
      and reliable food sites. Studies here reveal an important control element for
      ensuring that the route memories are used appropriately. They find that visual
      route memories can be disengaged, so that they do not provide guidance, even when
      all appropriate visual cues are present and when there are no competing guidance
      cues. Ants were trained along a simple route dominated by a single isolated
      landmark. If returning ants were caught just before entering the nest and
      replaced at the feeder, then they often interrupted the recapitulation of their
      homeward route with a period of apparent confusion during which the route
      memories were ignored. A series of experiments showed that this confusion
      occurred in response to the repetition of the route, and that the ants must
      therefore maintain some kind of a memory of their visual experience on the
      current trip home. A conceptual model of route guidance is offered to explain the
      results here. It proposes how the memory might act and suggests a general role
      for disengagement in regulating route guidance. 

PMID- 24870047
TI  - Experimental evolution of bet hedging under manipulated environmental uncertainty
      in Neurospora crassa.
AB  - All organisms are faced with environmental uncertainty. Bet-hedging theory
      expects unpredictable selection to result in the evolution of traits that
      maximize the geometric-mean fitness even though such traits appear to be
      detrimental over the shorter term. Despite the centrality of fitness measures to
      evolutionary analysis, no direct test of the geometric-mean fitness principle
      exists. Here, we directly distinguish between predictions of competing fitness
      maximization principles by testing Cohen's 1966 classic bet-hedging model using
      the fungus Neurospora crassa. The simple prediction is that propagule dormancy
      will evolve in proportion to the frequency of 'bad' years, whereas the prediction
      of the alternative arithmetic-mean principle is the evolution of zero dormancy as
      long as the expectation of a bad year is less than 0.5. Ascospore dormancy
      fraction in N. crassa was allowed to evolve under five experimental selection
      regimes that differed in the frequency of unpredictable 'bad years'. Results were
      consistent with bet-hedging theory: final dormancy fraction in 12 genetic
      lineages across 88 independently evolving samples was proportional to the
      frequency of bad years, and evolved both upwards and downwards as predicted from
      a range of starting dormancy fractions. These findings suggest that selection
      results in adaptation to variable rather than to expected environments. 

PMID- 24870048
TI  - Genetic mapping of the rice resistance-breaking gene of the brown planthopper
      Nilaparvata lugens.
AB  - Host plant resistance has been widely used for controlling the major rice pest
      brown planthopper (BPH, Nilaparvata lugens). However, adaptation of the wild BPH
      population to resistance limits the effective use of resistant rice varieties.
      Quantitative trait locus (QTL) analysis was conducted to identify resistance
      breaking genes against the anti-feeding mechanism mediated by the rice resistance
      gene Bph1. QTL analysis in iso-female BPH lines with single-nucleotide
      polymorphism (SNP) markers detected a single region on the 10th linkage group
      responsible for the virulence. The QTL explained from 57 to 84% of the total
      phenotypic variation. Bulked segregant analysis with next-generation sequencing
      in F2 progenies identified five SNPs genetically linked to the virulence. These
      analyses showed that virulence to Bph1 was controlled by a single recessive gene.
      In contrast to previous studies, the gene-for-gene relationship between the major
      resistance gene Bph1 and virulence gene of BPH was confirmed. Identified markers
      are available for map-based cloning of the major gene controlling BPH virulence
      to rice resistance. 

PMID- 24870049
TI  - Fairy wrasses perceive and respond to their deep red fluorescent coloration.
AB  - Fluorescence enables the display of wavelengths that are absent in the natural
      environment, offering the potential to generate conspicuous colour contrasts. The
      marine fairy wrasse Cirrhilabrus solorensis displays prominent fluorescence in
      the deep red range (650-700 nm). This is remarkable because marine fishes are
      generally assumed to have poor sensitivity in this part of the visual spectrum.
      Here, we investigated whether C. solorensis males can perceive the fluorescence
      featured in this species by testing whether the presence or absence of red
      fluorescence affects male-male interactions under exclusive blue illumination.
      Given that males respond aggressively towards mirror-image stimuli, we quantified
      agonistic behaviour against mirrors covered with filters that did or did not
      absorb long (i.e. red) wavelengths. Males showed significantly fewer agonistic
      responses when their fluorescent signal was masked, independent of brightness
      differences. Our results unequivocally show that C. solorensis can see its deep
      red fluorescent coloration and that this pattern affects male-male interactions.
      This is the first study to demonstrate that deep red fluorescent body coloration
      can be perceived and has behavioural significance in a reef fish. 

PMID- 24870050
TI  - Adenoviral vector delivery of RNA-guided CRISPR/Cas9 nuclease complexes induces
      targeted mutagenesis in a diverse array of human cells.
AB  - CRISPR/Cas9-derived RNA-guided nucleases (RGNs) are DNA targeting systems, which
      are rapidly being harnessed for gene regulation and gene editing purposes in
      model organisms and cell lines. As bona fide gene delivery vehicles, viral
      vectors may be particularly fit to broaden the applicability of RGNs to other
      cell types including dividing and quiescent primary cells. Here, the suitability
      of adenoviral vectors (AdVs) for delivering RGN components into various cell
      types is investigated. We demonstrate that AdVs, namely second-generation fiber
      modified AdVs encoding Cas9 or single guide RNA (gRNA) molecules addressing the
      Cas9 nuclease to the AAVS1 "safe harbor" locus or to a recombinant model allele
      can be produced to high-titers (up to 20 * 10(10) transducing units/ml).
      Importantly, AdV-mediated transduction of gRNA:Cas9 ribonucleoprotein complexes
      into transformed and non-transformed cells yields rates of targeted mutagenesis
      similar to or approaching those achieved by isogenic AdVs encoding TALENs
      targeting the same AAVS1 chromosomal region. RGN-induced gene disruption
      frequencies in the various cell types ranged from 18% to 65%. We conclude that
      AdVs constitute a valuable platform for introducing RGNs into human somatic cells
      regardless of their transformation status. This approach should aid investigating
      the potential and limitations of RGNs in numerous experimental settings. 

PMID- 24870051
TI  - Ozonolysis of methyl oleate monolayers at the air-water interface: oxidation
      kinetics, reaction products and atmospheric implications.
AB  - Ozonolysis of methyl oleate monolayers at the air-water interface results in
      surprisingly rapid loss of material through cleavage of the C=C bond and
      evaporation/dissolution of reaction products. We determine using neutron
      reflectometry a rate coefficient of (5.7 +/- 0.9) * 10(-10) cm(2) molecule(-1) s(
      1) and an uptake coefficient of ~3 * 10(-5) for the oxidation of a methyl ester
      monolayer: the atmospheric lifetime is ~10 min. We obtained direct experimental
      evidence that <2% of organic material remains at the surface on atmospheric
      timescales. Therefore known long atmospheric residence times of unsaturated fatty
      acids suggest that these molecules cannot be present at the interface throughout
      their ageing cycle, i.e. the reported atmospheric longevity is likely to be
      attributed to presence in the bulk and viscosity-limited reactive loss. Possible
      reaction products were characterized by ellipsometry and uncertainties in the
      atmospheric fate of organic surfactants such as oleic acid and its methyl ester
      are discussed. Our results suggest that a minor change to the structure of the
      molecule (fatty acid vs. its methyl ester) considerably impacts on reactivity and
      fate of the organic film.

PMID- 24870052
TI  - General route for preparing beta-nitrocarbonyl compounds using copper thermal
      redox catalysis.
AB  - Using a simple copper catalyst, the alkylation of nitroalkanes with alpha
      bromocarbonyls is now possible. This method provides a general, functional group
      tolerant route to beta-nitrocarbonyl compounds, including nitro amides, esters,
      ketones, and aldehydes. The highly sterically dense, functional group rich
      products from these reactions can be readily elaborated into a range of complex
      nitrogen-containing molecules, including highly substituted beta-amino acids. 

PMID- 24870053
TI  - Height dependent molecular trapping in stacked cyclic porphyrin nanorings.
AB  - Stacked layers of cyclic porphyrin nanorings constitute nanoscale receptacles
      with variable height and diameter which preferentially adsorb sublimed molecules.
      Using scanning tunnelling microscopy we determine the filling capacity of these
      nanoring traps, and the dependence of adsorbate capture on stack height and
      diameter. 

PMID- 24870054
TI  - Clinical roundtable monograph: CD30 in lymphoma: its role in biology, diagnostic
      testing, and targeted therapy.
AB  - CD30, a member of the tumor necrosis factor receptor superfamily, is a
      transmembrane glycoprotein receptor consisting of an extracellular domain, a
      transmembrane domain, and an intracellular domain. CD30 has emerged as an
      important molecule in the field of targeted therapy because its expression is
      generally restricted to specific disease types and states. The major cancers with
      elevated CD30 expression include Hodgkin lymphoma and anaplastic large T-cell
      lymphoma, and CD30 expression is considered essential to the differential
      diagnosis of these malignancies. Most commonly, CD30 expression is detected and
      performed by immunohistochemical staining of biopsy samples. Alternatively, flow
      cytometry analysis has also been developed for fresh tissue and cell aspiration
      specimens, including peripheral blood and bone marrow aspirate. Over the past
      several years, several therapeutic agents were developed to target CD30, with
      varying success in clinical trials. A major advance in the targeting of CD30 was
      seen with the development of the antibody-drug conjugate brentuximab vedotin,
      which consists of the naked anti-CD30 antibody SGN-30 conjugated to the synthetic
      antitubulin agent monomethyl auristatin E. In 2011, brentuximab vedotin was
      approved by the US Food and Drug Administration for use in Hodgkin lymphoma and
      anaplastic large cell lymphoma based on clinical trial data showing high response
      rates in these indications. Ongoing trials are examining brentuximab vedotin
      after autologous stem cell transplantation, as part of chemotherapy combination
      regimens, and in other CD30-expressing malignancies, including primary
      mediastinal large B-cell lymphomas, diffuse large B-cell lymphoma, lymphoma
      positive for Epstein-Barr virus, peripheral T-cell lymphoma not otherwise
      specified, and cutaneous anaplastic large cell lymphoma.

PMID- 24870059
TI  - Intentional thought dynamics during exercise performed until volitional
      exhaustion.
AB  - Using a non-linear approach, intentional dynamics of thoughts were examined
      during constant cycling performed until volitional exhaustion. Participants (n =
      12) completed two sessions at 80% Wmax. Their (1) intrinsic thought dynamics
      (i.e., no-imposed thoughts condition) and (2) intentional thought dynamics (i.e.,
      imposed task-unrelated thoughts condition; TUT) were recorded and then classified
      into four categories: internal and external TUT (TUT-I, TUT-E) and external and
      internal task-related thoughts (TRT-E, TRT-I). The probability estimates for
      maintaining each thought category stable, the rate of switching from one category
      to another, and the entropy dynamics along the testing procedure were assessed
      and compared through time phase. Friedman ANOVA tests revealed a significant
      effect of effort increase on thought contents only in the imposed TUT test. While
      TUT-I probabilities decreased significantly (P < .001) as effort increased, TRT-I
      probabilities increased (P < .05). Moreover, the entropy to the entire thought
      dynamics increased at the outset of task performance and decreased upon
      approaching volitional exhaustion (P < .001). As time spent in constant effort
      increased, and volitional exhaustion approached, task relatedness (TUT, TRT),
      direction (internal, external), and entropy of thought contents changed
      unintentionally providing further evidence for a nonlinear dynamics of attention
      focus.

PMID- 24870058
TI  - Remarkable reductions of PAKs in the brain tissues of scrapie-infected rodent
      possibly linked closely with neuron loss.
AB  - Prion diseases are irreversible progressive neurodegenerative diseases
      characterized in the brain by PrP(Sc) deposits, neuronal degeneration, gliosis
      and by cognitive, behavioral and physical impairments, leading to severe
      incapacity and inevitable death. Proteins of the p21-activated kinase (PAK)
      family are noted for roles in gene transcription, cytoskeletal dynamics, cell
      cycle progression and survival signaling. In the present study, we aimed to
      identify the potential roles of PAKs during prion infection, utilizing the brains
      of scrapie agent-infected hamsters. Western blots and immunohistochemical assays
      showed that brain levels of PAK3 and PAK1, as well as their upstream activator
      Rac/cdc42 and downstream substrate Raf1, were remarkably reduced at terminal
      stage. Double-stained immunofluorescent assay demonstrated that PAK3 was
      expressed mainly in neurons. Dynamic analyses of the brain samples collected at
      the different time points during the incubation period illustrated successive
      decreases of PAK3, PAK1 and Raf1, especially phosphor Raf1, which correlated well
      with neuron loss. Rac/cdc42 in the brain tissues increased at early stage and
      reached to the top at mid-late stage, but diminished at final stage. Unlike the
      alteration of PAKs in vivo, PAK3 and PAK1, as well as Rac/cdc42 and Raf1 in the
      prion-infected cell line SMB-S15 remained unchanged compared with those of its
      normal cell line SMB-PS. Our data here indicate that the functions of PAKs and
      their associated signaling pathways are seriously affected in the brains of prion
      disease, which appear to associate closely with the extensive neuron loss. 

PMID- 24870060
TI  - Prenatal polybrominated diphenyl ether exposures and neurodevelopment in U.S.
      children through 5 years of age: the HOME study.
AB  - BACKGROUND: Polybrominated diphenyl ethers (PBDEs) are persistent chemicals that
      have been widely used as flame retardants in furniture, carpet padding, car
      seats, and other consumer products during the past three decades. OBJECTIVE: We
      examined whether in utero exposure to PBDEs is associated with child cognitive
      function and behavior in a U.S. study sample. METHODS: In a prospective birth
      cohort, we measured maternal serum concentrations of BDE-47 and other PBDE
      congeners in 309 women at 16 weeks of gestation during 2003-2006 and followed
      their children in Cincinnati, Ohio. We measured cognitive and motor abilities
      using the Bayley Scales of Infant Development-II at ages 1, 2, and 3 years;
      intelligence using the Wechsler Preschool and Primary Scale of Intelligence-III
      at age 5 years; and children's behaviors using the Behavioral Assessment System
      for Children-2 annually at ages 2-5 years. We used linear mixed models or
      generalized estimating equations with adjustment for potential confounders to
      estimate associations between these outcomes and log10-transformed PBDE
      concentrations. RESULTS: The geometric mean of BDE-47 in maternal serum (20.1
      ng/g lipid) was comparable with U.S. adult national reference values. Prenatal
      BDE-47 was not significantly associated with Bayley Mental or Psychomotor
      Development Indices at 1-3 years, but a 10-fold increase in prenatal BDE-47 was
      associated with a 4.5-point decrease (95% CI: -8.8, -0.1) in Full-Scale IQ and a
      3.3-point increase (95% CI: 0.3, 6.3) in the hyperactivity score at age 5 years.
      CONCLUSIONS: Prenatal exposure to PBDEs was associated with lower IQ and higher
      hyperactivity scores in children.

PMID- 24870061
TI  - Comparison of gold nanoparticle mediated photoporation: vapor nanobubbles
      outperform direct heating for delivering macromolecules in live cells.
AB  - There is a great interest in delivering macromolecular agents into living cells
      for therapeutic purposes, such as siRNA for gene silencing. Although substantial
      effort has gone into designing nonviral nanocarriers for delivering
      macromolecules into cells, translocation of the therapeutic molecules from the
      endosomes after endocytosis into the cytoplasm remains a major bottleneck. Laser
      induced photoporation, especially in combination with gold nanoparticles, is an
      alternative physical method that is receiving increasing attention for delivering
      macromolecules in cells. By allowing gold nanoparticles to bind to the cell
      membrane, nanosized membrane pores can be created upon pulsed laser illumination.
      Depending on the laser energy, pores are created through either direct heating of
      the AuNPs or by vapor nanobubbles (VNBs) that can emerge around the AuNPs.
      Macromolecules in the surrounding cell medium can then diffuse through the pores
      directly into the cytoplasm. Here we present a systematic evaluation of both
      photoporation mechanisms in terms of cytotoxicity, cell loading, and siRNA
      transfection efficiency. We find that the delivery of macromolecules under
      conditions of VNBs is much more efficient than direct photothermal disturbance of
      the plasma membrane without any noticeable cytotoxic effect. Interestingly, by
      tuning the laser energy, the pore size could be changed, allowing control of the
      amount and size of molecules that are delivered in the cytoplasm. As only a
      single nanosecond laser pulse is required, we conclude that VNBs are an
      interesting photoporation mechanism that may prove very useful for efficient high
      throughput macromolecular delivery in live cells. 

PMID- 24870062
TI  - Induction of ganoderic acid biosynthesis by Mn2+ in static liquid cultivation of
      Ganoderma lucidum.
AB  - Metal ions affect cell physiology and metabolism significantly, but the role of
      Mn(2+) in the secondary metabolism of mushrooms is yet unclear. In static liquid
      cultivation of Ganoderma lucidum for producing antitumor ganoderic acids (GAs),
      the Mn(2+) addition was performed. Addition of 10 mM Mn(2+) at the start of the
      static liquid cultivation resulted in 2.2-fold improvement of total GAs
      production. The expression levels of GA biosynthetic and Ca(2+) sensors' genes
      were up-regulated with Mn(2+) induction while down-regulated by adding
      cyclosporin A (calcineurin inhibitor), suggesting that higher GA production might
      result from calcineurin signal regulation. Intracellular Ca(2+) imaging and
      calcineurin inhibitor study revealed that addition of Mn(2+) led to Ca(2+) influx
      from medium to the cells to trigger calcineurin signals. Mn(2+) addition was
      therefore an efficient induction strategy for improving GAs production, whose
      regulation mechanism was via calcineurin signaling transduction.

PMID- 24870063
TI  - The anchoring effect on the spin transport properties and I-V characteristics of
      pentacene molecular devices suspended between nickel electrodes.
AB  - Spin-polarized transport properties are determined for pentacene sandwiched
      between Ni surface electrodes with various anchoring ligands. These calculations
      are carried out using spin density functional theory in tandem with a non
      equilibrium Green's function technique. The presence of a Se atom at the edge of
      the pentacene molecule significantly modifies the transport properties of the
      device because Se has a different electronegativity than S. Our theoretical
      results clearly show a larger current for spin-up electrons than for spin-down
      electrons in the molecular junction that is attached asymmetrically across the Se
      linker at one side of the Ni electrodes (in an APL magnetic orientation).
      Moreover, this molecular junction exhibits pronounced NDR as the bias voltage is
      increased from 0.8 to 1.0 V. However, this novel NDR behavior is only detected in
      this promising pentacene molecular device. The NDR in the current-voltage (I-V)
      curve results from the narrowness of the density of states for the molecular
      states. The feasibility of controlling the TMR is also predicted in these
      molecular device nanostructures. Spin-dependent transmission calculations show
      that the sign and strength of the current-bias voltage characteristics and the
      TMR could be tailored for the organic molecule devices. These molecular junctions
      are joined symmetrically and asymmetrically between Ni metallic probes across the
      S and Se atoms (at the ends of the edges of the pentacene molecule). Our
      theoretical findings show that spin-valve phenomena can occur in these
      prototypical molecular junctions. The TMR and NDR results show that nanoscale
      junctions with spin valves could play a vital role in the production of novel
      functional molecular devices. 

PMID- 24870064
TI  - Topical corticosteroids do not revert the activated phenotype of eosinophils in
      eosinophilic esophagitis but decrease surface levels of CD18 resulting in
      diminished adherence to ICAM-1, ICAM-2, and endothelial cells.
AB  - Swallowed topical corticosteroids are the standard therapy for eosinophilic
      esophagitis (EoE) in adults. Eosinophils in the blood of untreated EoE patients
      have an activated phenotype. Our aim was to determine if corticosteroids restore
      the phenotype of eosinophils to a healthy phenotype and if certain cell-surface
      molecules on blood eosinophils correlate with eosinophilic infiltration of the
      esophagus. Levels of eight surface markers on eosinophils from treated and
      untreated EoE patients were determined by flow cytometry and analyzed using
      multivariate methods of pattern recognition. Corticosteroid-treated EoE patients'
      eosinophils had decreased levels of CD18 compared to both untreated patients and
      healthy controls, but maintained their activated phenotype. CD18 expression
      correlated positively with eosinophil numbers in the esophagus and promoted the
      adherence of eosinophils to ICAM-1, ICAM-2, and to endothelial cells. The
      diminished expression of CD18 may be one mechanism behind the reduced entry of
      eosinophils into the esophagus in corticosteroid-treated EoE patients. 

PMID- 24870066
TI  - Binding of human serum albumin to single-walled carbon nanotubes activated
      neutrophils to increase production of hypochlorous acid, the oxidant capable of
      degrading nanotubes.
AB  - Previous studies have shown that carboxylated single-walled carbon nanotubes
      (SWCNTs) can be catalytically biodegraded by hypochlorite (OCl-) and reactive
      radical intermediates of the human neutrophil enzyme myeloperoxidase (MPO).
      However, the importance of protein-SWCNT interactions in the biodegradation of
      SWCNTs was not stressed. Here, we used both experimental and theoretical
      approaches to investigate the interactions of SWCNTs with human serum albumin
      (HSA, one of the most abundant proteins in blood circulation) and found that the
      binding was involved in the electrostatic interactions of positively charged Arg
      residues of HSA with the carboxyls on the nanotubes, along with the pi-pi
      stacking interactions between SWCNTs and aromatic Tyr residues in HSA. Compared
      with SWCNTs, the binding of HSA could result in a reduced effect for OCl- (or the
      human MPO system)-induced SWCNTs degradation in vitro. However, the HSA-SWCNT
      interactions would enhance cellular uptake of nanotubes and stimulate MPO release
      and OCl- generation in neutrophils, thereby creating the conditions favorable for
      the degradation of the nanotubes. Upon zymosan stimulation, both SWCNTs and HSA
      SWCNTs were significantly biodegraded in neutrophils, and the degree of
      biodegradation was more for HSA-SWCNTs under these relevant in vivo conditions.
      Our findings suggest that the binding of HSA may be an important determinant for
      MPO-mediated SWCNT biodegradation in human inflammatory cells and therefore shed
      light on the biomedical and biotechnological applications of safe carbon
      nanotubes by comprehensive preconsideration of their interactions with human
      serum proteins.

PMID- 24870065
TI  - Shellfish Allergy: a Comprehensive Review.
AB  - Shellfish allergy is of increasing concern, as its prevalence has risen in recent
      years. Many advances have been made in allergen characterization. B cell epitopes
      in the major allergen tropomyosin have been characterized. In addition to
      tropomyosin, arginine kinase, sarcoplasmic calcium-binding protein, and myosin
      light chain have recently been reported in shellfish. All are proteins that play
      a role in muscular contraction. Additional allergens such as hemocyanin have also
      been described. The effect of processing methods on these allergens has been
      studied, revealing thermal stability and resistance to peptic digestion in some
      cases. Modifications after Maillard reactions have also been addressed, although
      in some cases with conflicting results. In recent years, new hypoallergenic
      molecules have been developed, which constitute a new therapeutic approach to
      allergic disorders. A recombinant hypoallergenic tropomyosin has been developed,
      which opens a new avenue in the treatment of shellfish allergy. Cross-reactivity
      with species that are not closely related is common in shellfish-allergic
      patients, as many of shellfish allergens are widely distributed panallergens in
      invertebrates. Cross-reactivity with house dust mites is well known, but other
      species can also be involved in this phenomenon.

PMID- 24870068
TI  - The role of mitochondria-derived reactive oxygen species in the pathogenesis of
      non-steroidal anti-inflammatory drug-induced small intestinal injury.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) have been implemented in clinical
      settings for a long time for their anti-inflammatory effects. With the number of
      NSAID users increasing, gastroenterological physicians and researchers have
      worked hard to prevent and treat NSAID-induced gastric mucosal injury, an effort
      that has for the large part being successful. However, the struggle against NSAID
      induced mucosal damage has taken on a new urgency due to the discovery of NSAID
      induced small intestinal mucosal injury. Although the main mechanism by which
      NSAIDs induce small intestinal mucosal injury has been thought to depend on the
      inhibitory effect of NSAIDs on cyclooxygenase (COX) activity, recent studies have
      revealed the importance of mitochondria-derived reactive oxygen species (ROS)
      production, which occurs independently of COX-inhibition. ROS production is an
      especially important factor in the increase of small intestinal epithelial cell
      permeability, an early stage in the process of small intestinal mucosal injury.
      By clarifying the precise mechanism, together with its clinical features using
      novel endoscopy, effective strategies for preventing NSAID-induced small
      intestinal damage, especially targeting mitochondria-derived ROS production, may
      be developed.

PMID- 24870069
TI  - An integrative appraisal of the diversification in the Atlantic forest genus
      Delomys (Rodentia: Cricetidae: Sigmodontinae) with the description of a new
      species.
AB  - Recent taxonomic studies on Neotropical mammals have benefited from the use of
      genetic data to unravel and recognize species diversity in a number of genera,
      including the Atlantic forest endemic genus Delomys. However, the success of this
      approach depends on ability to link genetically identified lineages to species
      names based on voucher specimens that lack genetic data. Cytogenetic studies in
      the Atlantic forest endemic rodent genus Delomys have revealed two widespread
      karyotypes, 2n=72/FN=90 and 2n=82/FN=80, which have been respectively ascribed to
      Delomys sublineatus (Thomas, 1903) and D. dorsalis (Hensel, 1872). More recently,
      a third karyotype, 2n=82/FN=86, reported from specimens collected on two
      montaintops in southeastern Brazil, was interpreted as evidence for a third
      species, D. collinus Thomas, 1917. This nominal form had originally been
      described as a subspecies of D. dorsalis from Itatiaia, one of the mountain
      ranges where the third karyotype was later detected. The detection of two
      sympatric karyotypes at the type locality of D. collinus in the Itatiaia mountain
      range, Southeastern Brazil, prompted a reevaluation of the association of
      karyomorphs and species names. In this paper, we assessed the congruence of
      molecular (cytochrome b), cytogenetic and morphological characters, to diagnose
      the species in the genus, including data from recently collected series and type
      specimens. Our results indicate that the genetic and morphological patterns are
      largely congruent with the recognition of three species, each of which is
      karyotypically and morphologically diagnosable. Our morphological analyses of
      sympatric samples from Itatiaia refute the former association of the 2n=82/FN=86
      karyotype with the holotype of D. dorsalis collinus (which is more similar to D.
      dorsalis with 2n=82/FN=80). Instead, we recognize and describe a new species for
      the 2n=82/FN=86 populations from the highest altitudinal zones of the Itatiaia
      and Caparao mountains. The geographical variation in D. dorsalis is also explored
      and the status of D. d. collinus is discussed in the light of the molecular and
      morphological evidence. Finally, we discuss biogeographic hypotheses concerning
      the disjunct distributions of D. dorsalis and the new species.

PMID- 24870070
TI  - Charletonia cameroonensis Haitlinger & Kekeunou sp. nov. and the first record of
      C. justynae Haitlinger, 1987 (Acari: Erythraeidae) from Cameroon with
      redescription of the species.
AB  - Charletonia cameroonensis Haitlinger & Kekeunou sp. nov. is described and
      illustrated from larvae obtained from Zonocerus variegatus (Linnaeus, 1758)
      (Orthoptera: Pyrgomorphidae) in Cameroon. For the first time C. justynae
      Haitlinger, 1987 is reported from Cameroon and from Z. variegatus and Eupezus
      rufipes Quedenfeldt, 1885 (Coleoptera: Tenebrionidae). This paper also presents
      new morphological data and a range of metric and meristic data for C. justynae.
      Distribution and hosts of Charletonia found on Orthoptera are given.

PMID- 24870071
TI  - A new species of Cyrtodactylus (Squamata: Gekkonidae) from Khammouane Province,
      Laos.
AB  - We describe a new species of the genus Cyrtodactylus based on two adult specimens
      from Khammouane Province, Laos. Cyrtodactylus jaegeri sp. nov. is distinguished
      from the remaining Indochinese bent-toed geckos by a combination of the following
      characters: a moderately sized Cyrtodactylus with a maximum SVL reaching 68.5 mm;
      dorsal pattern consisting of a dark nuchal loop and four narrow brown body bands
      between limb insertions; dorsal tubercles in 15-17 irregular rows; ventrals in 31
      32 longitudinal rows at midbody; lateral skin folds present with interspersed
      tubercles; precloacal-femoral pores 44 in the male, in a continuous series;
      enlarged femoral scales and precloacal scales present; postcloacal tubercles 3-6;
      subcaudals transversely enlarged. Cyrtodactylus jaegeri sp. nov. is the ninth
      species of Cyrtodactylus known from Laos.

PMID- 24870072
TI  - A new species of Hemiphyllodactylus Bleeker, 1860 (Squamata: Gekkonidae) from
      northwestern Thailand.
AB  - A new species of gekkonid, Hemiphyllodactylus chiangmaiensis sp. nov., from
      northwestern Thailand is separated from all other species of Hemiphyllodactylus
      by a set of features including: a maximum SVL of 41.2 mm; 8-12 chin scales
      extending transversely from unions of second and third infralabials and posterior
      margin of mental; lamellar formula on hand 3-3-3-3 or 3-4-3-3; lamellar formula
      on foot 3-3-3-3 or 3-4-4-4; continuous precloacal and femoral pores; a unique
      dorsal color pattern; and caecum and oviducts pigmented. These characters place
      this species in the speciose H. typus group. Hemiphyllodactylus chiangmaiensis
      sp. nov. fills a biogeographical hiatus in the distribution of this genus across
      northern Indochina. 

PMID- 24870067
TI  - Minimum information about a spinal cord injury experiment: a proposed reporting
      standard for spinal cord injury experiments.
AB  - The lack of reproducibility in many areas of experimental science has a number of
      causes, including a lack of transparency and precision in the description of
      experimental approaches. This has far-reaching consequences, including wasted
      resources and slowing of progress. Additionally, the large number of laboratories
      around the world publishing articles on a given topic make it difficult, if not
      impossible, for individual researchers to read all of the relevant literature.
      Consequently, centralized databases are needed to facilitate the generation of
      new hypotheses for testing. One strategy to improve transparency in experimental
      description, and to allow the development of frameworks for computer-readable
      knowledge repositories, is the adoption of uniform reporting standards, such as
      common data elements (data elements used in multiple clinical studies) and
      minimum information standards. This article describes a minimum information
      standard for spinal cord injury (SCI) experiments, its major elements, and the
      approaches used to develop it. Transparent reporting standards for experiments
      using animal models of human SCI aim to reduce inherent bias and increase
      experimental value.

PMID- 24870073
TI  - The genus Homaloxestis Meyrick (Lepidoptera: Lecithoceridae) from China, with
      descriptions of two new species.
AB  - Five species of the genus Homaloxestis Meyrick are recorded from China.
      Homaloxestis aciformis sp. nov. from Chongqing and H. ellipsoidea sp. nov. from
      Yunnan are described as new. Homaloxestis plocamandra (Meyrick, 1907), H.
      australis Park, 2004 and H. saitoi Park, 2004 are newly recorded from China.
      Photographs of adults and genital structures are provided. All the known species
      in China are listed.

PMID- 24870074
TI  - Benthodytes violeta, a new species of a deep-sea holothuroid (Elasipodida:
      Psychropotidae) from Mar del Plata Canyon (south-western Atlantic Ocean).
AB  - A new species of elasipodid holothuroid, Benthodytes violeta sp. nov., is
      described from the Mar del Plata Canyon off Buenos Aires Province (around 38oS
      54oW). It was taken at four locations at depths ranging from 1500 to 1950 m. This
      new species has a violet gelatinous body of up to 200 mm in length, with eight
      pairs of dorsal appendages, lateral festooned edges and four rows of tube feet
      ventrally. Body wall ossicles comprise rods and crosses with three or four arms
      and a central bipartite apophysis borne on the primary cross; tentacles and gonad
      deposits comprise rods and crosses with three and four arms. This is the first
      report of a holothuroid from the Mar del Plata Canyon area. 

PMID- 24870075
TI  - Isospora pitiguari n. sp. (Apicomplexa: Eimeriidae) from the rufous-browed
      peppershrike (Aves: Passeriformes: Vireonidae) Cyclarhis gujanensis Gmelin, 1789.
AB  - In the current study, a new coccidian species (Protozoa: Apicomplexa:
      Eimeriidae), collected from the rufous-browed peppershrike Cyclarhis gujanensis
      Gmelin, 1789, is reported from Brazil. Isospora pitiguari n. sp. has oocysts,
      which are spherical to sub-spherical, 26.8 * 25.7 MUm, with smooth, bilayered
      wall ~1.5 MUm thick. Micropyle, oocyst residuum, and polar granule are absent.
      Sporocysts are rounded to slightly ovoidal, 14.4 * 11.6 um. Stieda body flattened
      and substieda body prominent and rounded. Sporocyst residuum is composed of
      granules of different sizes. Sporozoites are vermiform with one refractile body
      and a nucleus. This is the first description of an isosporoid coccidium infecting
      a New World vireo. 

PMID- 24870076
TI  - Revision of the genus Phyrella (Holothuroidea: Dendrochirotida) with the
      description of a new species from Guam.
AB  - Recently collected material from Australia, Japan and Guam allowed us to revise
      Phyrella and describe Phyrella mookiei sp. nov. We redefine the genus based on
      combined morphological and molecular analyses. Phyrella unlike most
      dendrochirotids eviscerate posteriorly. The number of tentacles is variable (14
      20), as is the degree of fragmentation of the calcareous ring, calling into
      question the separation of Phyllophorinae and Semperiellinae, and suggest that
      Semperiella and Thyonidiella are synonymous with Phyrella. We recognize five
      species in Phyrella (Phyllophorus trapezus Clark, 1932, Phyllophorus fragilis
      Mitsukuri & Ohshima, 1912 (synonymized with Thyonidiella oceana Heding & Panning,
      1954), Phyllophorus thyonoides Clark, 1938, Semperiella drozdovi Levin &
      Stepanov, 1999, and Phyrella mookiei), assign three others provisionally
      (Lipotrapeza ambigua Cherbonnier, 1988 (synonymized with Phyllophorus contractura
      Cherbonnier, 1988 and Thyonidiella cherbonnieri Rowe & Richmond, 2004),
      Phyllophorus bedoti Koehler, 1895, and Orcula tenera Ludwig, 1875), considering
      the last two species inquirenda. Phyrella aculeatus (Ludwig, 1894), is
      transferred to Euthyonidiella. Orcula (Phyllophorus?) dubia Bedford, 1899,
      Thyonidiella exigua Cherbonnier, 1988 and Thyonidiella kungi O'Loughlin, 2012 are
      provisionally transferred to Phyllophorus sensu lato, the first is considered
      species inquirenda. Molecular phylogenetic analysis recovers a well-supported
      Phyrella, but suggests that some genera and subfamilies of Phyllophoridae are not
      monophyletic.

PMID- 24870077
TI  - New and rare sponges from the deep shelf of the Alboran Island (Alboran Sea,
      Western Mediterranean).
AB  - The sponge fauna from the deep shelf (70 to 200 m) of the Alboran Island (Alboran
      Sea, Western Mediterranean) was investigated using a combination of ROV surveys
      and collecting devices in the frame of the EC LIFE+ INDEMARES Grant aimed to
      designate marine areas of the Nature 2000 Network within Spanish territorial
      waters. From ROV surveys and 351 examined specimens, a total of 87 sponge species
      were identified, most belonging in the Class Demospongiae, and one belonging in
      the Class Hexactinellida. Twenty six (29%) species can be regarded as either
      taxonomically or faunistically relevant. Three of them were new to science
      (Axinella alborana nov. sp.; Axinella spatula nov. sp.; Endectyon filiformis nov.
      sp.) and 4 others were Atlantic species recorded for the first time in the
      Mediterranean Sea (Jaspis eudermis Levi & Vacelet, 1958; Hemiasterella elongata
      Topsent, 1928; Axinella vellerea Topsent, 1904; Gelliodes fayalensis Topsent,
      1892). Another outstanding finding was a complete specimen of Rhabdobaris
      implicata Pulitzer-Finali, 1983, a species only known from its holotype, which
      had entirely been dissolved for its description. Our second record of the species
      has allowed a neotype designation and a restitution of the recently abolished
      genus Rhabdobaris Pulitzer-Finally, 1983, also forcing a slight modification of
      the diagnosis of the family Bubaridae. Additionally, 12 species were recorded for
      the first time from the shelf of the Alboran Island, including a few individuals
      of the large hexactinellid Asconema setubalense Kent, 1877 that provided the
      second Mediterranean record of this "North Atlantic" hexactinellid. ROV
      explorations also revealed that sponges are an important component of the deep
      shelf benthos, particularly on rocky bottoms, where they make peculiar sponge
      gardens characterized by a wide diversity of small, erect species forming a dense
      "undergrowth" among a scatter of large sponges and gorgonians. The great
      abundance and the taxonomic singularities of the sponge fauna occurring in these
      deep-shelf bottoms strongly suggest these habitats to be considered within the
      environmental protection of the Nature 2000 Network. 

PMID- 24870078
TI  - Rhynchelmis subgenus Sutroa Eisen new rank, with two new species from western
      North America (Annelida, Clitellata, Lumbriculidae).
AB  - The lumbriculid Rhynchelmis subgenus Sutroa Eisen, 1888 new rank is defined for a
      group of Nearctic species having multiple diverticula originating at the
      spermathecal ducts and eversible penial bulbs. Characters are confirmed in
      specimens of the type species, Rhynchelmis (Sutroa) rostrata (Eisen, 1888),
      collected from the type locality. Rhynchelmis (Sutroa) klamathensis Fend n. sp.
      is described from open water benthic habitats in Upper Klamath Lake, Oregon, USA.
      It resembles other R. (Sutroa) species in the paired spermathecal diverticula,
      the spermathecal and penial bulbs, the histological structure of the atria, the
      nonfunctional anterior male funnels, and the arrangement of blood vessels.
      Rhynchelmis klamathensis differs from all Nearctic Rhynchelmis in lacking a
      filiform proboscis. The combination of large body size, the elongate spermathecal
      ducts with paired and usually unbranched diverticula, the highly contorted atria,
      and the complex male pores with conical penes also distinguish typical R.
      klamathensis from other Rhynchelmis species. Smaller specimens with otherwise
      similar morphology, from the Sacramento River Delta, California, are also
      assigned to this species. Rhynchelmis (Sutroa) diespluviae Fend n. sp. is
      described from several stream sites, mostly in northern Idaho, USA. Rhynchelmis
      diespluviae differs from closely related species in morphology of the conical
      penes, and in the structure and anterolateral position of the paired
      spermathecae. 

PMID- 24870079
TI  - Revision of the Old World Sobarocephala (Diptera: Clusiidae).
AB  - The Old World Sobarocephala Czerny, 1903 are revised, with 16 of the 29 known
      species described here as new: S. anonymos spec. nov., S. apoxys spec. nov., S.
      cycla spec. nov., S. doryphoros spec. nov., S. insolata spec. nov., S. kapnikos
      spec. nov., S. laticrinis spec. nov., S. magna spec. nov., S. myllolabis spec.
      nov., S. nebulosa spec. nov., S. nimbipennis spec. nov., S. orientalis spec.
      nov., S. paksana spec. nov., S. recava spec. nov., S. secaperas spec. nov., and
      S. triangula spec. nov. Species are mostly Oriental and Afrotropical in
      distribution, but species also occur in Japan, Nepal and northern Australia.
      Species mostly belong to the exclusively Old World S. plumicornis species group,
      but there are also representatives from the predominantly New World S. flava and
      S. flaviseta groups. Sobarocephala is described for the first time from
      Australia, China, Laos, Sri Lanka, Madagascar and West Africa. A key and
      illustrations are provided. 

PMID- 24870080
TI  - Four new species of Andricus Hartig oak gallwasp from Turkey (Hymenoptera:
      Cynipidae, Cynipini).
AB  - Four new species of oak gallwasps, Andricus ahmeti, A. anatolicus, A. bakrachus
      and A. turcicus (Hymenoptera: Cynipidae: Cynipini) are described from Turkey. All
      four species are known only from asexual females and induce galls on twigs and
      young shoots on Q. infectoria, Q. macranthera and Q. petraea. Data on the
      diagnosis, distribution and biology of the four new species are given. Andricus
      stonei and Aphelonyx kordestanica are listed for the first time for the Turkish
      oak gallwasp fauna. 

PMID- 24870081
TI  - Three new species of Coecobrya (Collembola: Entomobryidae) from southern and
      northwest China.
AB  - Three new species of Coecobrya are described from southern and northwest China.
      C. draconis sp. nov. from Guangxi cave shows some troglomorphic features, such as
      the inner ungual teeth inserted basally. C. xui sp. nov. is similar to C. huangi
      and differs from the latter by head and tergal chaetotaxy. C. qin sp. nov. is the
      second member of the genus with 3+3 eyes, but cannot be assigned to either the
      tenebricosa- or boneti-groups because it has eyes and a large outer tooth on
      unguiculus.

PMID- 24870082
TI  - Review of the millipede genus Epanerchodus Attems, 1901 in continental China,
      with descriptions of new species (Diplopoda: Polydesmidae).
AB  - Four new species of Epanerchodus are described from mainland China: E. jaegeri
      sp. nov. and E. martensi sp. nov., both sympatric and even partly syntopic in
      Shaanxi, E. schawalleri sp. nov., from Sichuan, and E. yunnanensis sp. nov., from
      Yunnan. In addition, E. koreanus Verhoeff, 1937 is formally new to the fauna of
      China due to fresh samples from Jilin. A key is presented to all 14 unquestioned
      species of Epanerchodus currently known from mainland China.

PMID- 24870083
TI  - A striking new genus and species of tiger-moth (Lepidoptera: Erebidae, Arctiinae,
      Arctiini) from the Caribbean, with molecular and morphological analysis of its
      systematic placement.
AB  - Westindia Vincent, a new genus, is proposed for W. haxairei Vincent, a new
      species of Neotropical tiger-moth described from Dominican Republic. Habitus,
      male and female genitalia are described and figured. The systematic position of
      the new genus within Arctiinae is discussed in light of a comparative morphology
      and a molecular phylogeny derived from the DNA barcode fragment of the
      mitochondrial COI gene and of the D2 region of the 28S rDNA gene. 

PMID- 24870084
TI  - Nomenclatural notes on some checkered beetle (Coleoptera: Cleridae) types of the
      Natural History Museum, London (BMNH).
AB  - Lectotypes were designated (and holotypes and paralectotypes recognized) for 44
      species of Hydnocerinae, including the type species for Isolemidia, Parmius,
      Paupris, Allelidea, Blaesiopthalmus and Lemidia, four species of Enoclerus
      (Clerinae), and 14 species of Cymatodera (Tillinae). Annotations include comments
      on additional type material, new type locality, previous (type series) locality,
      and questionable or mysterious types. Phyllobaenus pallipes (Gorham) and P.
      rufithorax (Gorham) are synonymized with P. flavifemoratus (Gorham), P. chapini
      (Wolcott) is synonymized under P. lateralis (Gorham), and P. villosus
      (Schenkling) is synonymized under P. longus (LeConte), new synonymies.
      Phyllobaenus longus (LeConte) is discovered in New Mexico, new state record.

PMID- 24870085
TI  - Steinernema poinari sp. n. (Nematoda: Steinernematidae) a new entomopathogenic
      nematode from the Czech Republic.
AB  - A new steinernematid nematode, herein described as Steinernema poinari sp. n.,
      was recovered by baiting soil samples with the last instar wax moth larvae
      Galleria mellonella in three localities of southwest Bohemia, Czech Republic.
      Morphological and molecular data confirmed this nematode as a new species which
      belongs to the affine/intermedium group. S. poinari sp. n. was characterized by
      male, female and infective juvenile morphological observations. Male spicules are
      robust with a pointed tip, SW% = 109 (98-123) and GS% = 70 (58-87). The tail
      terminus of the first generation have a papillated mucron, whereas in the second
      generation a short filamentous mucron sometimes develops. Females of the first
      generation have a moderately protruding vulva, postanal swelling absent or
      slightly developed. Second generation females have a long filamentous mucron on
      the tail tip. Infective juvenile have a body length of 768 um, lateral field
      formula 2, 5, 6, 5, 2, 1, ratio D% of 46 (40-55), E% of 84 (76-95) and H% of 50
      (43-56). The new species was characterized by sequences of ITS and D2D3 regions
      of ribosomal DNA. S. poinari sp. n. can also be separated from S. affine and S.
      intermedium by cross-breeding tests.

PMID- 24870086
TI  - Taxonomic study of Chinese species of the genus Macropsis Lewis, 1836 (Hemiptera:
      Cicadellidae: Macropsinae) III: a review of oak-dwelling species.
AB  - The group of Chinese Macropsis species dwelling on oak (Quercus spp.) is reviewed
      and nine species are recognized. Among them, three new species, Macropsis
      huangbana sp. nov. from Shaanxi and Yunnan Provinces, M. latiprocessa sp. nov.
      from Guizhou Province and M. longiprocessa sp. nov. from Yunnan Province, are
      described and illustrated; M. irenae Viraktamath, 1981 (= M. irrorata Tishechkin,
      2002, nec Matsumura, 1912) is recorded from China and Japan for the first time;
      M. meifengensis Huang & Viraktamath, 1993 and M. jozankeana (Matsumura, 1912) are
      redescribed based on examination of specimens from mainland China and adjacent
      territories of Russia respectively; translation of the original description of M.
      rubrosternalis Kuoh, 1992 from Chinese is provided, also a key to species of Oak
      dwelling Macropsis from China is present.

PMID- 24870087
TI  - First stage zoeal morphology of four ghost crabs Ocypode ceratophthalmus (Pallas,
      1772), O. cordimanus Latreille, 1818, O. sinensis Dai, Song & Yang, 1985 and O.
      stimpsoni Ortmann, 1897 (Crustacea, Decapoda, Ocypodidae).
AB  - Light and scanning electron microscopy (SEM) were used to examine the first zoeal
      stage of four ghost crabs, Ocypode ceratophthalmus (Pallas, 1772), O. cordimanus
      Latreille, 1818, O. sinensis Dai, Song & Yang, 1985 and O. stimpsoni Ortmann,
      1897. Finding diagnostic characters to distinguish between the four species
      proved difficult because their setal appendage patterns were identical. However
      the rectangular and pockmarked patterns on the ventral carapace are rather
      pronounced in O. ceratophthalmus and O. stimpsoni but weak in O. cordimanus and
      O. sinensis. The spinulation on the furca of the telson is less in O. cordimanus
      than in the other three species.

PMID- 24870088
TI  - Ancyronyx reticulatus and A. pulcherrimus, two new riffle beetle species from
      Borneo, and discussion about elmid plastron structures (Coleoptera: Elmidae).
AB  - Two new species of Ancyronyx Erichson, 1847 (Coleoptera: Elmidae) are described
      from Borneo: A. pulcherrimus (Brunei) and A. reticulatus (Sabah). Habitus views,
      illustrations of important characters as well as plastron structures of Ancyronyx
      reticulatus are presented and discussed.

PMID- 24870089
TI  - A new stygobitic species of Stygocarididae (Crustacea: Anaspidacea) from South
      America.
AB  - The only South American Anaspidacean families are the Stygocarididae Noodt and
      the monotipic Patagonaspididae Grosso & Peralta. I describe a new Stygocarididae,
      Parastygocaris luisgrossoi n. sp. from the hyporheic zone of a stream in Sierra
      de San Luis, Argentina. The main characters of the new species include: antennula
      outer flagellum with 9-10 articles, sexual dimorphism in flagella; antenna with 4
      segmented peduncle and 5-articulate flagellum; maxilla with row of 8 setae along
      inner margin of proximal endite; uropod: inner margin of protopod with 7-8 setae
      and distal segment of exopod lined by 7 setae; pereopod 6 female with 1 long
      plumose seta on basis. The morphology and chaetotaxy of the new taxon is compared
      with congeneric species. The long evolutionary history of the Gondwanan
      Anaspidacea and the accompanying fauna of the new species, suggest the probable
      existence of an ancient groundwater basin in western Argentina, south of 28oS
      that would have harboured interstitial fauna of great and diverse antiquity.

PMID- 24870090
TI  - Geometric morphometry and molecular analysis clarified the identity of Opius sp.
      aff. bellus (Hymenoptera, Braconidae), a fruit fly parasitoid in Brazil.
AB  - The aim of this study was to clarify the identity of specimens designated as
      Opius sp. aff. bellus using geometric morphometry and analysis of the ITS2 region
      of the ribosomal DNA (rDNA) and region D2 of the 28S rDNA. Opius bellus Gahan is
      a koinobiont endoparasitoid of fruit fly larvae (Diptera: Tephritidae)
      exclusively found in the Neotropical region, but widely distributed from Mexico
      to Argentina. Opius sp. aff. bellus is morphologically similar to Opius bellus
      but exhibits yellowish, instead of dark-brown, posterior tibiae. Twenty
      anatomical landmarks on the wings from these two taxa sampled from three
      Brazilian states were analyzed. Multivariate morphometric analysis showed a large
      amount of morphological similarity between the specimens, indicating they are the
      same species. Sequence analysis of the ITS2 showed that intrapopulation
      variability was similar to interpopulation variability and that the morphotypes
      were also highly similar. In addition, the D2 region of the 28S rDNA displayed
      high similarity between sequences. Therefore, based on morphometric and molecular
      analyses, specimens thought to be Opius sp. aff. bellus actually belong to O.
      bellus.  

PMID- 24870091
TI  - Trimma helenae (Pisces; Gobioidei), a new species of gobiid fish from Indonesia.
AB  - A new species of Trimma, T. helenae, is described from the southeastern lagoon at
      Penemu Island off the southwest coast of Waigeo, Raja Ampat, Indonesia. The new
      species has a unique colour pattern when alive, consisting of a yellow anterior
      half and red posterior half, with four small white spots along the midline of the
      dorsal and ventral surfaces of the caudal peduncle. It is also the only species
      of the genus to have a nasal sac that is flush with the snout surface (not raised
      above the level of the snout or only represented by a nasal pit), and which lacks
      a raised rim to the posterior nasal pore. Trimma helenae belongs to a group of 12
      valid nominal species defined by having a broad bony interorbital region (width
      80-100% of pupil diameter), but differs from all of but three of these in having
      only cycloid scales in the midline and on the sides of the nape. The other
      members of the group have mostly ctenoid scales in this region. 

PMID- 24870092
TI  - On taxonomy of Hydrobaenus fries, 1830 (Diptera: Chironomidae: Orthocladiinae)
      from the Russian Far East, with a key to species.
AB  - Additions and corrections to the diagnosis of the genus Hydrobaenus, a
      redescription for adult male and immature stages of H. distinctus (Makarchenko et
      Makarchenko) comb. n. , a taxonomic notes to H. jacuticus Makarchenko et
      Makarchenko and identification keys of adult males, pupae and larvae of
      Hydrobaenus species from the Russian Far East are given. 

PMID- 24870093
TI  - Five new species of Qadria Mahmood (Hemiptera: Cicadellidae: Typhlocybinae) from
      China.
AB  - Five new leafhopper species, Qadria bannaensis, Q. daliensis, Q. dongfanga, Q.
      guiyanga and Q. cucullata spp. nov. from Yunnan, Hainan and Guizhou Prov. of
      China are described and illustrated, and a key to all species of the genus Qadria
      is provided.

PMID- 24870094
TI  - A new species of Psorodonotus (Orthoptera, Tettigoniidae) from Anatolia, Turkey.
AB  - Descriptions of a new species of Tettigoniinae; Psorodonotus suphani sp. n. from
      Turkey were given. The relationships between the new species and closest taxa
      (morphologically and geographically) were evaluated by using morphological
      characters. Ultimately, some remarkable points of the distribution pattern of the
      species were presented. 

PMID- 24870096
TI  - Four new species of Tonnoira Enderlein (Diptera: Psychodidae: Psychodinae) from
      the Brazilian Atlantic forest.
AB  - Four species of Tonnoira from the Brazilian Atlantic forest are described and
      illustrated: Tonnoira brisolaii sp. nov, Tonnoira ferreirai sp. nov., Tonnoira
      andradei sp. nov. and Tonnoira galatiae sp. nov.  

PMID- 24870095
TI  - Record of Natula matsuurai Sugimoto (Orthoptera: Gryllidae: Trigonidiinae) and
      other sword-tailed crickets from India.
AB  - The genus Natula is a new record from the state of Rajasthan, India. Description
      of the species has been supported with photographs and line drawings leading to
      its identification. The other common sword-tailed crickets of the sub-family
      Trigonidiinae have also been described. 

PMID- 24870097
TI  - Description of Conchyliurus dispar n. sp. (Copepoda, Cyclopoida, Clausidiidae)
      associated with the bivalve Barnea manilensis (Philippi) from the Yellow Sea with
      a discussion of the male morphotypes in the genus.
AB  - Conchyliurus dispar, a new species associated with the bivalve Barnea manilensis
      (Philippi), is described from the intertidal zone of the Yellow Sea. The new
      species is distinguished from its congeners by a combination of the following
      characters: the absence of posterolateral processes on the male genital somite,
      the absence of a dorsal lobe on the female genital double-somite, and the
      presence of proximal spinules on the ventral surface of the anal somite. Based on
      a review of the literature on Conchyliurus, we also argue that the male of the
      new species and possibly all other known species of Conchyliurus consist of two
      distinct morphotypes, a large male and a small male.  

PMID- 24870098
TI  - New short-horned flies (Diptera: Eremochaetidae) from the Early Cretaceous of
      China.
AB  - Eremochaetidae is a rare family found from the Late Jurassic to the Early
      Cretaceous. So far, only 8 genera with 12 species have been recorded. Herein, we
      describe a new species, Dissup clausus sp. nov., and the first male of Eremomukha
      (E.) tsokotukha Mostovski, 1996, from the Yixian Formation, the Early Cretaceous
      of Northeastern China. Additionally, E. (E.) insidiosa Mostovski, 1996 is
      considered as a new synonym of E. (E.) tsokotukha. An updated list of all known
      Eremochaetidae is presented. 

PMID- 24870099
TI  - Review of the genus Andrioplecta Obraztsov (Lepidoptera: Tortricidae:
      Olethreutinae) from China.
AB  - The Chinese species of Andrioplecta Obraztsov, 1968 are reviewed. Six species are
      treated, including one new species (A. angusticuculla, sp. nov.) and three
      species newly recorded from China (A. phuluangensis, A. shoreae and A.
      suboxystaura). Images and descriptions of adults and genitalia are provided,
      along with a key to the species in China. 

PMID- 24870100
TI  - Taxonomic note: the fossil clawed lobster, Metanephrops elongatus Hu & Tao, 2000
      (Nephropidae), is a nomen dubium but definitely not a Metanephrops.

PMID- 24870101
TI  - Baeotingis Drake & Poor, 1939 and Coleopterodes Philippi, 1864 (Hemiptera:
      Heteroptera: Tingidae): first genera records for Brazil from Pampa.

PMID- 24870102
TI  - An annotated and revised checklist of pleurostome ciliates (Protista: Ciliophora:
      Litostomatea) from Slovakia, Central Europe.
AB  - Pleurostomatids are predatory ciliates, living especially in the periphyton and
      benthos of various freshwater and marine habitats. In the present work, we
      provide an annotated and revised checklist of this ciliate group from the
      territory of Slovakia. Altogether 29 pleurostome species belonging to five genera
      have been reported there: Acineria incurvata, Ac. punctata, Ac. uncinata,
      Amphileptus claparedii, Am. falcatus, Am. fusiformis, Am. parafusidens, Am.
      pleurosigma, Am. procerus, Am. punctatus, A. rotundus, Litonotus alpestris, Li.
      anguilla, Li. carinatus, Li. crystallinus, Li. cygnus, Li. fasciola, Li.
      fusidens, Li. hirundo, Li. lamella, Li. minisculus, Li. muscorum, Li. obtusus,
      Li. triqueter, Li. varsaviensis, Loxophyllum helus, Lo. meleagris, Lo. rostratum,
      and Siroloxophyllum utriculariae. We have catalogued these records providing the
      following data for each species: (1) author(s) and date of publication; (2)
      name(s) of the species as appeared in the publication(s) followed by
      chronologically listed references including relevant page(s) in literature; (3)
      nomenclatural and taxonomic notes if needed; (4) main morphological characters;
      (5) morphological data on Slovak populations if available; and (6) all faunistic
      records. 

PMID- 24870103
TI  - New Oriental tribe Iscini, new non-dilatognathan species of Notophlebia Peters &
      Edmunds 1970 and independent origin of Dilatognathus-type mouth apparatus in
      Atalophlebiinae (Ephemeroptera: Leptophlebiidae).
AB  - A new tribe, Iscini tr. n., comprising the Oriental genera Isca Gillies 1951 and
      Notophlebia Peters & Edmunds 1970, is established. A new species, Notophlebia
      ganeshi sp. n., is described based on male and female imagos reared from larvae.
      The new species markedly differs from N. jobi Sivaramakrishnan & Peters 1984 by
      its non-specialized larval mouth apparatus. The larva of N. jobi has a highly
      specialized mouth apparatus of the "Dilatognathus-type"; this type of mouth
      apparatus has evolved independently in several non-related leptophlebiid taxa. 

PMID- 24870104
TI  - A new species of Hemiphyllodactylus Bleeker, 1860 (Squamata: Gekkonidae) from Ba
      Na-Nui Chua Nature Reserve, Central Vietnam.
AB  - A new species of the gekkonid Hemiphyllodactylus banaensis sp. nov. is described
      from Ba Na-Nui Chua Nature Reserve in central Vietnam. Previously included within
      H. yunnanensis, the new species is distinguished from all other congeners by
      having the unique combination of a maximum SVL of 48.2 mm in males and 51.0 mm in
      females; seven chin scales extending transversely from the union of the first and
      second infralabials and posterior margin of mental; enlarged postmental scales; 9
      12 supralabials; 9-11 infralabials; 18-20 longitudinally arranged dorsal scales
      at midbody contained within one eye diameter; 20-21 precloacal and femoral pore
      bearing scales contiguous in males and 0-20 contiguous pore-bearing precloacal
      scales in females; dorsal pattern on body composed of transverse blotches and two
      whitish stripes across shoulder extending to sacrum; postsacral mark whitish
      brown and bearing anteriorly projecting arms; and caecum and oviducts
      unpigmented. 

PMID- 24870105
TI  - A new species of eriophyoid mite, Aceria tripuraensis sp. n. (Acari:
      Eriophyoidea), on Hibiscus macrophyllus from India.
AB  - A new species of Eriophyidae (Acari: Prostigmata: E riophyoidea) mite, Aceria
      tripuraensis n. sp., is described from the closed bud galls of Hibiscus
      macrophyllus Roxb. ex Hornem. (Malvaceae) in India. Aceria tripuraensis n. sp. is
      distinguished by having a prodorsal shield with distinct rounded lobes on the
      postero-lateral margins and two pairs of submedian lines. The tarsal solenidia
      with unusual transverse sculptures, are 2.5x longer than the empodia. Twenty
      Aceria species are now known to inhabit malvaceous plant hosts and those are
      listed here along with type localities and host plant details. A key to all known
      species of Aceria recorded from Hibiscus spp. is also provided. 

PMID- 24870106
TI  - Taxonomic notes on some species and subspecies of aphids (Hemiptera: Aphididae).
AB  - Subspecies Dysaphis pavlovskiana indica Chakrabarti & Medda, 1993 is given
      species status (Dysaphis indica Chakrabarti & Medda, 1993, new status). Aphis
      plantaginis asiatica Daniyarova, 1979 is a synonym of Aphis taraxacicola (Borner,
      1940). The nomen nudum Uroleucon (Uromelan) lehri Zaitzev, Lelej, Storozhenko &
      Kurzenko, 2006 is recognized as referring to Uroleucon (Uromelan) campanulae
      (Kaltenbach, 1843). 

PMID- 24870107
TI  - Two new species of Thraulodes Ulmer, 1920 (Ephemeroptera: Leptophlebiidae:
      Atalophlebiinae) from Southeast Brazil.
AB  - Two new species of Thraulodes Ulmer, 1920 are described from Rio de Janeiro and
      Sao Paulo, Southeastern Brazil, based on male and female imagos. Thraulodes
      luisae sp. nov. differs from all other species of the genus by the short and wide
      penes spines, turning up to apex; triangular shape of styliger plate with median
      projection abrupt and short with rounded apex; abdominal and legs color pattern;
      and presence of 2-3 weakly marked cross veins basal to bullae. Thraulodes pinga
      sp. nov. differs from all other species of the genus by the wide shape of
      styliger plate with median projection short with wide base and truncated apex;
      abdominal and legs color pattern; and presence of 1 weakly marked cross vein
      basal to bullae.  

PMID- 24870108
TI  - Potamalpheops tyrymembe sp. n.: the first southwestern Atlantic species of the
      shrimp genus Potamalpheops Powell, 1979 (Caridea: Alpheidae).
AB  - A new species of the alpheid shrimp genus Potamalpheops Powell, 1979, P.
      tyrymembe sp. n., is described based on several specimens collected from burrows
      of the ucidid crab Ucides cordatus (Linnaeus, 1763) and other, unknown burrowing
      decapods, on a mangrove flat between the Baiano and Serra rivers, Povoado de
      Tremembe, Marau, state of Bahia, Brazil (14o08'51.9"S, 39o05'04.4"W). The new
      species belongs to the P. monodi (Sollaud, 1932) species group, based on the
      presence of two pairs of spiniform setae on the distal margin of the telson and
      non-enlarged male chelipeds. It is characterized by a short rostrum and absence
      of setae on the pterygostomial angle of the carapace. 

PMID- 24870109
TI  - Three new species in the leafhopper genus Pedionis Hamilton (Hemiptera:
      Cicadellidae: Macropsinae) from China, with a key to Chinese species.
AB  - Three new species, Pedionis (Pedionis) tribrachyblasta, P. (P.) dentiforma and P.
      (P.) dinghuensis spp. nov. are recorded from China. Images of adults and
      genitalia of the three species are provided, with a key to distinguish all male
      species in this genus from China.  

PMID- 24870110
TI  - Designation of type genus for the holothuroid family Cucumellidae (Echinodermata
      : Holothuroidea : Dendrochirotida) with re-examination of the holotype of
      Cucumella decaryi Cherbonnier.
AB  - Thandar & Arumugam (2011), in their erection of the new dactylochirotid family
      Cucumellidae, inadvertently omitted to designate its type genus. This error is
      here rectified and Cucumella Heding (in Ludwig & Heding, 1935) is designated the
      type genus of the new family Cucumellidae to comply with the requirements of
      Article 61 of the International Code. Following Smirnov (2012), in his revised
      classification of the Holothuroidea, the new family is now classified in the
      order Dendrochirotida. In addition, the holotype of Cucumella decaryi Cherbonnier
      is re-examined to confirm its synonymy with Neostichopus grammatus (H.L. Clark). 

PMID- 24870112
TI  - Association between nocturnal hypoxia and liver injury in the setting of
      nonalcoholic fatty liver disease.
AB  - PURPOSE: Obstructive sleep apnea (OSA) is suggested as a potential risk factor of
      nonalcoholic fatty liver disease (NAFLD). However, the underlying mechanism is
      still far from clear. The aim of this observational study was to investigate the
      influence of OSA-related hypoxia on severity of liver injury in patients with
      NAFLD. METHODS: Consecutive patients with ultrasound-diagnosed NAFLD who
      underwent standard polysomnography were enrolled. Fasting blood samples were
      obtained from all patients for biological profile measurements, and demographic
      data were collected. Subjects were divided into control, moderate, and severe
      groups. RESULTS: A total of 85 subjects with 73 males and 12 females were
      included (mean age, 44.67 +/- 1.28 years; mean body mass index, 27.28 +/- 0.33
      kg/m(2)). Alanine aminotransferase (ALT), aspartate aminotransferase (AST),
      ALT/AST, gamma glutamyltransferase, total cholesterol, low density lipoprotein
      cholesterol, fasting glucose, and high-sensitivity C-reactive protein
      significantly increased with the aggravation of OSA. In multivariate analysis,
      oxygen desaturation index was the major contributing factor for elevated ALT
      (beta = 0.435, p = 0.000), average O2 saturation was the major independent
      predictor of elevated AST (beta = -0.269, p = 0.020). CONCLUSIONS: OSA-related
      hypoxia was independently associated with the biochemical evidence of liver
      injury in the presence of NAFLD.

PMID- 24870114
TI  - Many double mastectomies are not clinically indicated, study finds.

PMID- 24870113
TI  - Oral appliance effectively reverses Muller's maneuver-induced upper airway
      collapsibility in obstructive sleep apnea and hypopnea syndrome.
AB  - OBJECTIVES: To verify the effects of oral appliance (OA) on upper airway
      morphology under intraluminal pressure, identify specific sites of upper airway
      collapsibility that can be reversed by OAs, and determine the relationship
      between OA efficacy and dynamic upper airway changes using computed tomography
      (CT) with Muller's maneuver. MATERIALS AND METHODS: Nineteen adult Chinese
      patients with symptomatic mild-to-moderate sleep apnea were recruited from our
      sleep center. Each patient was fitted with a two-piece OA. Dynamic changes in the
      retropalatal and retroglossal airway were evaluated using CT at end-expiration
      and during Muller's maneuver, both with and without an OA. RESULTS: Upper airway
      changes in the end-expiration phase before OA placement did not significantly
      differ from those after OA placement. However, under intraluminal pressure
      induced by Muller's maneuver, OA effectively expanded the upper airway at
      multiple levels. In addition, OA counteracted negative intraluminal pressure more
      effectively in the retropalatal region than in the retroglossal region, with
      95.65, 68.75, 72.41, and 78.38 % improvements in the collapsibility index of the
      anteroposterior dimension, transverse dimension, minimum cross-sectional area,
      and volume of the retropalatal region, respectively. Both nonresponders and
      responders to OA treatment were sensitive to the intraluminal pressure induced by
      Muller's maneuver. However, the collapsibility of the retropalatal airway
      improved significantly only in the responders, not in the nonresponders.
      CONCLUSIONS: OA effectively treats OSAHS by improving upper airway
      collapsibility.

PMID- 24870117
TI  - Applying the precautionary principle to nutrition and cancer.
AB  - PRIMARY OBJECTIVE: Research has identified certain foods and dietary patterns
      that are associated with reduced cancer risk and improved survival after cancer
      diagnosis. This research has formed the basis for dietary guidance issued by
      cancer organizations. Unfortunately, gaps within nutrition research have made it
      difficult to make recommendations in some areas. This review specifies suggested
      dietary guidance in which evidence of a dietary influence on cancer risk is
      substantial, even if not conclusive. Evidence summaries within the review are
      based on the 2007 report of the World Cancer Research Fund/American Institute for
      Cancer Research. This review also describes advantages and disadvantages of
      following the suggested dietary guidance and includes putative mechanisms
      involved in cancer progression. MAIN OUTCOMES AND RESULTS: Suggested dietary
      guidance where evidence is sufficiently compelling include (1) limiting or
      avoiding dairy products to reduce the risk of prostate cancer; (2) limiting or
      avoiding alcohol to reduce the risk of cancers of the mouth, pharynx, larynx,
      esophagus, colon, rectum, and breast; (3) avoiding red and processed meat to
      reduce the risk of cancers of the colon and rectum; (4) avoiding grilled, fried,
      and broiled meats to reduce the risk of cancers of the colon, rectum, breast,
      prostate, kidney, and pancreas; (5) consumption of soy products during
      adolescence to reduce the risk of breast cancer in adulthood and to reduce the
      risk of recurrence and mortality for women previously treated for breast cancer;
      and (6) emphasizing fruits and vegetables to reduce risk of several common forms
      of cancer. CONCLUSION: By adopting the precautionary principle for nutrition
      research, this review aims to serve as a useful tool for practitioners and
      patients.

PMID- 24870115
TI  - Cardiac structure and function improvements in coronary artery disease combined
      with severe obstructive sleep apnea/hypopnea syndrome patients via noninvasive
      positive pressure ventilation therapy.
AB  - OBJECTIVE: The aim of this study was to investigate the effects of a noninvasive
      positive pressure ventilation therapy on cardiac structure and function in
      patients with coronary heart disease combined with obstructive sleep
      apnea/hypopnea syndrome (OSAHS). PATIENTS AND METHODS: Eighty patients with
      coronary heart disease OSAHS were divided randomly into treatment (n=40) and
      control (n=40) groups. Both groups received standard medications. The treatment
      group received additional noninvasive mechanical ventilation support for at least
      3 h (3-6 h) every night. On the first day after selection and 3 months
      afterwards, participants were examined with echocardiograms, 24-h ambulatory
      blood pressure monitoring, and blood analyses. Primary endpoints were left
      ventricular end-diastolic diameter, left ventricular end-systolic diameter, left
      ventricular ejection fraction, left atrial diameter as well as serum
      concentrations of N-terminal prohormone of brain natriuretic peptide, and high
      sensitive C-reactive protein. Secondary endpoints included cardiac death,
      nonfatal myocardial infarction, and hospitalization. RESULTS: After the 3-month
      study period, patients in the treatment group showed significantly improved left
      ventricular end-diastolic diameter (P=0.02), left ventricular end-systolic
      diameter (P=0.035), left ventricular ejection fraction (P=0.05), and left atrial
      diameter (P=0.02) values, and their serum N-terminal prohormone of brain
      natriuretic peptide (P=0.01) and high-sensitive C-reactive protein (P=0.04)
      concentrations were significantly improved compared with the control group.
      During the 3 months, three cardiovascular complications occurred in the treatment
      group versus nine in the control group (P<0.05). CONCLUSION: For patients with
      coronary heart disease combined with OSAHS, noninvasive mechanical ventilation
      therapy can significantly improve heart functions and reduce the occurrence of
      cardiovascular complications.

PMID- 24870119
TI  - Relationship Between Percutaneous Procedures and Lumbar Infections Based on Data
      From The National Health Insurance Review & Assessment Service of Korea.
AB  - STUDY DESIGN: A study from the National health insurance database. OBJECTIVE: To
      investigate the relationship between percutaneous procedures or open surgeries
      and spinal infections using the 5-year large unit national dataset. SUMMARY OF
      BACKGROUND DATA: There is no nation-based research data on the relationship
      between percutaneous procedures and spinal infections in Korea. MATERIALS AND
      METHODS: This study used disease codes (ICD-10: International Classification of
      Disease) and operation fee codes (national medical insurance) registered in the
      National Health Insurance Review & Assessment Service for the 5 years from 2007
      to 2011. Using the above disease codes, the number of each percutaneous
      procedure, open surgery, and the number of lumbar infections were investigated by
      the regional and national units, and the relationship between procedures or open
      surgeries and lumbar infection was compared statistically. RESULTS: Lumbar
      infection showed a gradual growing annual trend, with a 3-fold increase in 2011
      compared with 2007. Percutaneous procedures (nerve blocks) increased by
      approximately 2.6 times over 4 years. Kyphoplasty tended to decrease each year.
      Open surgeries (posterior fusion, discectomy, and laminectomy) were at a similar
      level each year. Lumbar infection and percutaneous procedures were positively
      correlated, and a negative correlation was observed between kyphoplasty and open
      surgeries. The incidence of lumbar infection was higher in large cities than
      provinces and increased 2-3 times in 2011 compared with 2007 in all regions.
      CONCLUSIONS: There was no significant difference in the number of open surgeries
      for the 5-year study, but the number of percutaneous procedures (nerve blocks)
      increased each year, showing an approximate 4-fold increase in 4 years. Lumbar
      infection showed a positive correlation with percutaneous procedures, and
      kyphoplasty and open surgeries were negatively correlated. Therefore, as
      selective nerve block procedure is also considered an important factor affecting
      the growing trend of lumbar infections, unnecessary procedures should be avoided
      to reduce the absolute number of infections.

PMID- 24870120
TI  - Cost-Utility Analysis of 1- and 2-Level Dorsal Lumbar Fusions With and Without
      Recombinant Human Bone Morphogenic Protein-2 at 1-Year Follow-Up.
AB  - STUDY DESIGN: A retrospective 1-year cost-utility analysis. OBJECTIVE: To
      determine the cost-effectiveness of using recombinant human bone morphogenic
      protein (rhBMP-2) in addition to autograft for 1- and 2-level lumbar fusions.
      SUMMARY OF BACKGROUND DATA: rhBMP-2 has been studied extensively to identify its
      benefits, risks, patient outcomes, and costs relative to autograft [local bone or
      iliac crest bone graft (ICBG)]. This study seeks to analyze the cost
      effectiveness of adding rhBMP-2 to autograft versus without rhBMP-2 in lumbar
      fusions. METHODS: Thirty-three patients receiving rhBMP-2 in addition to either
      local bone autograft or ICBG (rhBMP-2 cohort) and 42 patients receiving only
      local bone autograft or ICBG (control cohort) for 1- or 2-level dorsal lumbar
      fusion were analyzed. This included posterolateral fusion, posterior lumbar
      interbody fusion, and transforaminal lumbar interbody fusion. One-year
      postoperative health outcomes were assessed based on Visual Analogue Scale, Pain
      Disability Questionnaire, Patient Health Questionnaire, and EuroQol-5 Dimensions
      questionnaires. Direct medical costs were estimated using Medicare national
      payment amounts and indirect costs were based on patient missed work days and
      patient income. Postoperative 1-year cost-utility ratios and the incremental cost
      effectiveness ratio (ICER) were calculated to assess for cost-effectiveness using
      a threshold of $100,000/QALY gained. RESULTS: The 1-year cost-utility ratio
      (total cost/DeltaQALY) for the control cohort was significantly lower
      ($143,251/QALY gained) than that of the rhBMP-2 cohort ($272,414/QALY gained)
      (P<0.01). At 1-year follow-up, the control group dominated the ICER compared with
      the rhBMP-2 group. CONCLUSIONS: Statistically significant and clinically relevant
      improvements (through minimum clinically important differences) were seen for
      both cohorts. In the ICER analysis, the control cohort dominated the rhBMP-2
      group. Assuming durable per year gains in QALY, by 2 years fusion with autograft
      but without rhBMP-2 would be considered cost-effective ($71,625/QALY gained),
      whereas fusion with both autograft and rhBMP-2 would not be cost-effective
      ($136,207/QALY gained).

PMID- 24870124
TI  - Light harvesting in a fluctuating antenna.
AB  - One of the major players in oxygenic photosynthesis, photosystem II (PSII),
      exhibits complex multiexponential fluorescence decay kinetics that for decades
      has been ascribed to reversible charge separation taking place in the reaction
      center (RC). However, in this description the protein dynamics is not taken into
      consideration. The intrinsic dynamic disorder of the light-harvesting proteins
      along with their fluctuating dislocations within the antenna inevitably result in
      varying connectivity between pigment-protein complexes and therefore can also
      lead to nonexponential excitation decay kinetics. On the basis of this
      presumption, we propose a simple conceptual model describing excitation diffusion
      in a continuous medium and accounting for possible variations of the excitation
      transfer rates. Recently observed fluorescence kinetics of PSII of different
      sizes are perfectly reproduced with only two adjustable parameters instead of the
      many decay times and amplitudes required in standard analysis procedures; no
      charge recombination in the RC is required. The model is also able to provide
      valuable information about the structural and functional organization of the
      photosynthetic antenna and in a straightforward way solves various contradictions
      currently existing in the literature. 

PMID- 24870123
TI  - Beat processing is pre-attentive for metrically simple rhythms with clear
      accents: an ERP study.
AB  - The perception of a regular beat is fundamental to music processing. Here we
      examine whether the detection of a regular beat is pre-attentive for metrically
      simple, acoustically varying stimuli using the mismatch negativity (MMN), an ERP
      response elicited by violations of acoustic regularity irrespective of whether
      subjects are attending to the stimuli. Both musicians and non-musicians were
      presented with a varying rhythm with a clear accent structure in which
      occasionally a sound was omitted. We compared the MMN response to the omission of
      identical sounds in different metrical positions. Most importantly, we found that
      omissions in strong metrical positions, on the beat, elicited higher amplitude
      MMN responses than omissions in weak metrical positions, not on the beat. This
      suggests that the detection of a beat is pre-attentive when highly beat inducing
      stimuli are used. No effects of musical expertise were found. Our results suggest
      that for metrically simple rhythms with clear accents beat processing does not
      require attention or musical expertise. In addition, we discuss how the use of
      acoustically varying stimuli may influence ERP results when studying beat
      processing. 

PMID- 24870126
TI  - Electronic confinement in graphene ruled by N doped extended defects.
AB  - We investigate by means of ab-initio simulations the formation energy and the
      electronic properties of substitutional N doping in graphene with distinct grain
      boundary defects as a function of the N concentration. Our results show that the
      presence of substitutional N atoms along the defective regions is quite likely
      for several N concentrations. Also, we find either semiconducting or metallic
      structures, depending on the N concentration. Confinement effects were also
      investigated for the semiconducting structures. We find that the distance between
      the defect lines can modulate the band structure of those semiconducting N doped
      lines. This opens an interesting possibility to produce two-dimensional
      heterojunctions composed by N doped grain boundaries with different distances
      between the defect lines. 

PMID- 24870127
TI  - From the phenotype to the genotype via bioinformatics.
AB  - Moving a project from the status of observing a trait of interest to identifying
      the underlying causal variant is a challenging task requiring a series of
      bioinformatics procedures and ideally the availability of a suitable reference
      genome sequence and its associated resources. We visit common practices for
      discovering the biology underlying observed traits in mammals. 

PMID- 24870128
TI  - Production and analytic bioinformatics for next-generation DNA sequencing.
AB  - The bioinformatics requirements within the clinical environment are very
      specific, and analytic techniques need to be fit for purpose, robust, and
      predictable. At the same time, the bewildering amount of information produced
      during these analyses needs to be carefully managed, used and interpreted
      correctly. The challenge for clinical laboratories now is to implement production
      analytical processes that are capable of handling different experimental
      approaches on current equipment, as well as to incorporate ways for these systems
      to evolve to take account of developments likely to make impacts in the near
      future. This is complicated by the many options available at each of the critical
      processing steps and a clear method needs to be developed to assemble appropriate
      pipelines. Here, I discuss the issues relevant to the development of an
      informatics pipeline that meets these criteria that should allow individual
      laboratories to assess their proposed strategies. 

PMID- 24870129
TI  - Analyzing the metabolome.
AB  - Metabolites, the chemical entities that are transformed during metabolism,
      provide a functional readout of cellular biochemistry that offers the best
      prediction of the phenotype and the nature of a disease. Mass spectrometry now
      allows thousands of metabolites to be quantitated. The targeted or untargeted
      data from metabolic profiling can be combined with either supervised or
      unsupervised approaches to improve interpretation. These sophisticated
      statistical techniques are computationally intensive. This chapter reviews
      techniques applicable to metabolomics approaches to disease. 

PMID- 24870125
TI  - Dissemination of periodontal pathogens in the bloodstream after periodontal
      procedures: a systematic review.
AB  - BACKGROUND: To date, there is no compilation of evidence-based information
      associating bacteremia and periodontal procedures. This systematic review aims to
      assess magnitude, duration, prevalence and nature of bacteremia caused by
      periodontal procedures. STUDY DESIGN: Systematic Review. TYPES OF STUDIES
      REVIEWED: MEDLINE, EMBASE and LILACS databases were searched in duplicate through
      August, 2013 without language restriction. Observational studies were included if
      blood samples were collected before, during or after periodontal procedures of
      patients with periodontitis. The methodological quality was assessed in duplicate
      using the modified Newcastle-Ottawa scale (NOS). RESULTS: Search strategy
      identified 509 potentially eligible articles and nine were included. Only four
      studies demonstrated high methodological quality, whereas five were of medium or
      low methodological quality. The study characteristics were considered too
      heterogeneous to conduct a meta-analysis. Among 219 analyzed patients, 106
      (49.4%) had positive bacteremia. More frequent bacteria were S. viridans, A.
      actinomycetemcomitans P. gingivalis, M. micros and species Streptococcus and
      Actinomyces, although identification methods of microbiologic assays were
      different among studies. CLINICAL IMPLICATIONS: Although half of the patients
      presented positive bacteremia after periodontal procedures, accurate results
      regarding the magnitude, duration and nature of bacteremia could not be
      confidentially assessed.

PMID- 24870130
TI  - Statistical perspectives for genome-wide association studies (GWAS).
AB  - In this chapter we consider some key elements in conducting a successful genome
      wide association study or GWAS. The first step is to design the study well
      (Subheading 3.1), paying particular attention to case and control selection and
      achieving adequate sample size to deal with the large burden of multiple testing.
      Second, we focus on the crucial step of applying stringent quality control
      (Subheading 3.2) to genotyping results. The most crucial potential confounding
      factor in GWAS is population stratification, and we describe methods for
      accounting for this in study design and analysis (Subheading 3.3). The primary
      association analysis is relatively straightforward, and we describe the main
      approaches to this, including evaluation of results (Subheading 3.4). More
      comprehensive coverage of the genome can be achieved by using an external
      reference panel to estimate genotypes at untyped variants using imputation
      (Subheading 3.5), which we consider in some detail. We finish with some
      observations on following up a GWAS (Subheading 3.6).

PMID- 24870131
TI  - Bioinformatics challenges in genome-wide association studies (GWAS).
AB  - Genome-wide association studies (GWAS) are a powerful tool for investigators to
      examine the human genome to detect genetic risk factors, reveal the genetic
      architecture of diseases and open up new opportunities for treatment and
      prevention. However, despite its successes, GWAS have not been able to identify
      genetic loci that are effective classifiers of disease, limiting their value for
      genetic testing. This chapter highlights the challenges that lie ahead for GWAS
      in better identifying disease risk predictors, and how we may address them. In
      this regard, we review basic concepts regarding GWAS, the technologies used for
      capturing genetic variation, the missing heritability problem, the need for
      efficient study design especially for replication efforts, reducing the bias
      introduced into a dataset, and how to utilize new resources available, such as
      electronic medical records. We also look to what lies ahead for the field, and
      the approaches that can be taken to realize the full potential of GWAS.

PMID- 24870132
TI  - Studying cancer genomics through next-generation DNA sequencing and
      bioinformatics.
AB  - Cancer is a complex disease driven by multiple mutations acquired over the
      lifetime of the cancer cells. These alterations, termed somatic mutations to
      distinguish them from inherited germline mutations, can include single-nucleotide
      substitutions, insertions, deletions, copy number alterations, and structural
      rearrangements. A patient's cancer can contain a combination of these
      aberrations, and the ability to generate a comprehensive genetic profile should
      greatly improve patient diagnosis and treatment. Next-generation sequencing has
      become the tool of choice to uncover multiple cancer mutations from a single
      tumor source, and the falling costs of this rapid high-throughput technology are
      encouraging its transition from basic research into a clinical setting. However,
      the detection of mutations in sequencing data is still an evolving area and
      cancer genomic data requires some special considerations. This chapter discusses
      these aspects and gives an overview of current bioinformatics methods for the
      detection of somatic mutations in cancer sequencing data. 

PMID- 24870133
TI  - Using bioinformatics tools to study the role of microRNA in cancer.
AB  - High-throughput sequencing (HTS) has emerged as a promising method to study gene
      expression in neoplastic and normal tissues. Using HTS, many research groups have
      described transcript variants as well as discovering new transcribed loci and
      noncoding RNAs, including microRNAs. In oncology, expression profiling of
      microRNAs in matched tumor and normal tissues has been used to detect
      differential expression of microRNAs in cancer. We present one approach for
      laboratories with few bioinformatics support to assist in the analysis of
      microRNA HTS data focused in oncology. This approach can also be adapted to study
      other systems. 

PMID- 24870134
TI  - Chromosome microarrays in diagnostic testing: interpreting the genomic data.
AB  - DNA-based Chromosome MicroArrays (CMAs) are now well established as diagnostic
      tools in clinical genetics laboratories. Over the last decade, the primary
      application of CMAs has been the genome-wide detection of a particular class of
      mutation known as copy number variants (CNVs). Since 2010, CMA testing has been
      recommended as a first-tier test for detection of CNVs associated with
      intellectual disability, autism spectrum disorders, and/or multiple congenital
      anomalies...in the post-natal setting. CNVs are now regarded as pathogenic in 14
      18 % of patients referred for these (and related) disorders.Through consideration
      of clinical examples, and several microarray platforms, we attempt to provide an
      appreciation of microarray diagnostics, from the initial inspection of the
      microarray data, to the composing of the patient report. In CMA data
      interpretation, a major challenge comes from the high frequency of clinically
      irrelevant CNVs observed within "patient" and "normal" populations. As might be
      predicted, the more common and clinically insignificant CNVs tend to be the
      smaller ones <100 kb in length, involving few or no known genes. However, this
      relationship is not at all straightforward: CNV length and gene content are only
      very imperfect indicators of CNV pathogenicity. Presently, there are no reliable
      means of separating, a priori, the benign from the pathological CNV classes.This
      chapter also considers sources of technical "noise" within CMA data sets. Some
      level of noise is inevitable in diagnostic genomics, given the very large number
      of data points generated in any one test. Noise further limits CMA resolution,
      and some miscalling of CNVs is unavoidable. In this, there is no ideal solution,
      but various strategies for handling noise are available. Even without solutions,
      consideration of these diagnostic problems per se is informative, as they afford
      critical insights into the biological and technical underpinnings of CNV
      discovery. These are indispensable to any clinician or scientist practising
      within the field of genome diagnostics.

PMID- 24870135
TI  - Bioinformatics approach to understanding interacting pathways in neuropsychiatric
      disorders.
AB  - Bioinformatics-based applications have been incorporated into several medical
      disciplines, including cancer, neuroscience, and recently psychiatry. Both the
      increasing interest in the molecular aspect of neuropsychiatry and the
      availability of high-throughput discovery and analysis tools have encouraged the
      incorporation of bioinformatics and neurosystems biology techniques into
      psychiatry and neuroscience research. As applied to neuropsychiatry, systems
      biology involves the acquisition and processing of high-throughput datasets to
      infer new information. A major component in bioinformatics output is pathway
      analysis that provides an insight into and prediction of possible underlying
      pathogenic processes which may help understand disease pathogenesis. In addition,
      this analysis serves as a tool to identify potential biomarkers implicated in
      these disorders. In this chapter, we summarize the different tools and algorithms
      used in pathway analysis along with their applications to the different layers of
      molecular investigations, from genomics to proteomics.

PMID- 24870136
TI  - Pathogen genome bioinformatics.
AB  - Recent advances in DNA sequencing technology have made the whole-genome
      sequencing of pathogens in a clinically relevant turn-around time both
      technically and economically feasible. The DNA sequencing of pathogens with
      epidemic potential offers new and exciting opportunities for high-resolution
      public health surveillance. This chapter outlines major methods and
      bioinformatics tools for pathogen genome characterization, the identification of
      infectious disease clusters, as well as for genomics-guided biosurveillance.
      Existing challenges are also considered. 

PMID- 24870137
TI  - Setting up next-generation sequencing in the medical laboratory.
AB  - The introduction of next-generation sequencing (NGS) technologies in research has
      proven to be very successful in the past 8 years. Now, there is considerable
      demand to apply these technologies for clinical diagnosis. The translation of
      research-to-clinical practice brings with it a unique set of challenges,
      particularly when it comes to setting up NGS in the medical laboratory. The
      practical issues related to infrastructure, selecting which NGS platform, and
      dealing with informatics requirements are discussed. Application of NGS for
      clinical diagnosis requires robust quality assurance at multiple levels including
      sample assessment, library preparation, template generation, and sequencing data
      which need to be generated, analyzed, and stored. The requirements for data
      generation, analysis, and storage are considerable. 

PMID- 24870138
TI  - Managing incidental findings in exome sequencing for research.
AB  - Exome sequencing for research has become available for broadly based genomic
      studies as well as smaller targeted investigations. New exome research projects
      being considered will intentionally process a large amount of common and rare DNA
      variation for the purpose of finding specific links between genotype and
      phenotype. However, the risks of uncovering a clinically relevant incidental
      finding are not uniform across projects but are highly dependent on the question
      being asked and exactly how it is intended to be answered.Factors that influence
      the possibility of revealing a clinically relevant incidental DNA variation
      include the following: The overall design of the study and the number of
      participants involved, the mode of inheritance of the phenotype including whether
      the phenotype is likely to have a monogenic or a complex inheritance, whether the
      study is assessing a known list of genes or not, and whether the causative DNA
      variation is likely to be rare or common. Importantly, differing bioinformatics
      DNA variant filtering strategies strongly influence the odds of discovering an
      incidental finding. This chapter provides a framework for understanding and
      assessing the likelihood of discovering clinically relevant, incidental DNA
      variations that are not directly related to the question being addressed in a
      particular exome research project. It also outlines DNA variant filtering and
      functional informatics approaches that can investigate specific genomic questions
      while minimizing the risks of uncovering an incidental finding. 

PMID- 24870139
TI  - Approaches for classifying DNA variants found by Sanger sequencing in a medical
      genetics laboratory.
AB  - Diagnostic applications of DNA sequencing technologies present a powerful tool
      for the clinical management of patients. Applications range from better
      diagnostic classification to identification of therapeutic options, prediction of
      drug response and toxicity, and carrier testing. Although the advent of massively
      parallel sequencing technologies has increased the complexity of clinical
      interpretation of sequence variants by an order of magnitude, the annotation and
      interpretation of the clinical effects of identified genomic variants remain a
      challenge regardless of the sequencing technologies used to identify them. Here,
      we survey methodologies which assist in the diagnostic classification of DNA
      variants and propose a practical decision analytic protocol to assist in the
      classification of sequencing variants in a clinical setting. The methods include
      database queries, software tools for protein consequence, evolutionary
      conservation and pathogenicity prediction, familial segregation, case-control
      studies, and literature review. These methods are deliberately pragmatic as
      diagnostic constraints of clinically useful turnaround times generally preclude
      obtaining evidence from in vivo or in vitro functional experiments for variant
      assessment. Clinical considerations require that variant classification is
      stringent and rigorous, as misinterpretation may lead to inappropriate clinical
      consequences; thus, multiple parameters and lines of evidence are considered to
      determine potential biological significance. 

PMID- 24870140
TI  - Designing algorithms for determining significance of DNA missense changes.
AB  - Humans differ from each other in their genomes by <1 %. This determines the
      difference in susceptibility to disease, phenotypes, and traits. Predominantly,
      when looking for causal disease mutations, protein-coding sequences are screened
      first since those have the highest probability of affecting the function of a
      protein. Recent technological advances have seen a rise in the number of
      experiments being conducted to study a variety of diseases from monogenic to
      complex traits. Several computational approaches have been developed to extract
      putative functional missense variants. In this chapter we review some of these
      approaches and describe a standard step-by-step procedure that can be used to
      classify variants for the purpose of clinical care. We also provide two examples
      demonstrating this approach, one for a patient with a dilated cardiomyopathy
      diagnosis, and the other for a patient with an unknown etiology undergoing whole
      genome sequencing (WGS). 

PMID- 24870141
TI  - DNA variant databases: current state and future directions.
AB  - In this chapter we aim to provide an overview of DNA variant databases, commonly
      known as Locus-Specific Databases (LSDBs), or Gene-Disease Specific Databases
      (GDSDBs), but the term variant database will be used for simplicity. We restrict
      this overview to germ-line variants, particularly as related to Mendelian
      diseases, which are diseases caused by a variant in a single gene. Common
      difficulties associated with variant databases and some proposed solutions are
      reviewed. Finally, systems where technical solutions have been implemented are
      discussed. This work will be useful for anyone wishing to establish their own
      variant database, or to learn about the global picture of variant databases, and
      the technical challenges to be overcome.

PMID- 24870142
TI  - Natural language processing in biomedicine: a unified system architecture
      overview.
AB  - In contemporary electronic medical records much of the clinically important data
      signs and symptoms, symptom severity, disease status, etc.-are not provided in
      structured data fields but rather are encoded in clinician-generated narrative
      text. Natural language processing (NLP) provides a means of unlocking this
      important data source for applications in clinical decision support, quality
      assurance, and public health. This chapter provides an overview of representative
      NLP systems in biomedicine based on a unified architectural view. A general
      architecture in an NLP system consists of two main components: background
      knowledge that includes biomedical knowledge resources and a framework that
      integrates NLP tools to process text. Systems differ in both components, which we
      review briefly. Additionally, the challenge facing current research efforts in
      biomedical NLP includes the paucity of large, publicly available annotated
      corpora, although initiatives that facilitate data sharing, system evaluation,
      and collaborative work between researchers in clinical NLP are starting to
      emerge.

PMID- 24870143
TI  - Candidate gene discovery and prioritization in rare diseases.
AB  - A rare or orphan disorder is any disease that affects a small percentage of the
      population. Most genes and pathways underlying these disorders remain unknown.
      High-throughput techniques are frequently applied to detect disease candidate
      genes. The speed and affordability of sequencing following recent technological
      advances while advantageous are accompanied by the problem of data deluge.
      Furthermore, experimental validation of disease candidate genes is both time
      consuming and expensive. Therefore, several computational approaches have been
      developed to identify the most promising candidates for follow-up studies. Based
      on the guilt by association principle, most of these approaches use prior
      knowledge about a disease of interest to discover and rank novel candidate genes.
      In this chapter, a brief overview of some of the in silico strategies for
      candidate gene prioritization is provided. To demonstrate their utility in rare
      disease research, a Web-based computational suite of tools that use integrated
      heterogeneous data sources for ranking disease candidate genes is used to
      demonstrate how to run typical queries using this system. 

PMID- 24870144
TI  - Computer-aided drug designing.
AB  - Computer-aided drug designing has emerged as a cost-effective and rapid tool for
      the discovery of newer therapeutic agents. Several algorithms have been developed
      to analyze protein structure and function, to identify interacting ligands,
      active site residues, and to study protein-ligand interactions, which can
      eventually lead to the identification of new drugs. In silico drug designing
      involves identification of the target protein which is responsible for the
      development of the disease under study. The three-dimensional structure of the
      protein can be predicted using homology modeling, while molecular docking is
      applied to study the interaction of a drug molecule with the protein. The best
      orientation of the ligand-protein docked structure which has overall minimum
      energy needs to be obtained. In silico methods can be used to identify potential
      drugs for various diseases. Thus, computer-aided drug designing has become an
      indispensible and integral part of the drug discovery process. 

PMID- 24870147
TI  - Diffusion and dissemination of a family peer-education program on mental
      disorders: a case study of the Omotenashi--Family Experiences Learning Program.
AB  - OBJECTIVES: The families of people with mental illnesses need sufficient
      opportunities to learn about such illnesses. Therefore, a family peer-education
      program about mental disorders, the Omotenashi - Family Experiences Learning
      Program, has been developed in Japan following the design of similar programs in
      the U.S. and Hong Kong. We aimed to clarify the factors related to the diffusion
      and dissemination of the program and to identify areas for improvement in its
      dissemination strategies. METHODS: This report was a case study based on the
      conceptual framework of the diffusion and dissemination of innovation in a health
      care organization. The conceptual framework incorporates the adoption and
      routinization of the innovations by individuals and organizations in the external
      context. Interview data from fifteen family members in three family groups that
      had adopted the program were analyzed. They were interviewed about their
      backgrounds, the adoption of the program, and their experiences with the program
      implementation. We extracted descriptions based on the conceptual framework from
      the transcribed interview data and classified them into the framework components.
      We also compared the processes of adoption and routinization employed by the
      three family groups. RESULTS: Adoption processes were affected by the sense of
      crisis caused by decreased membership, member aging, and the necessity of policy
      change in family groups as well as the anticipation that the program may solve
      problems and the strength of the leader's intention to change and sustain the
      family group. Cooperative families and sufficient funding were necessary for the
      adoption of the program. Support from relevant organizational staff encouraged
      the family groups to adopt the program. Adopters encountered difficulties in
      gaining program participants but continued to take part in the program after
      realizing their anticipated positive results and receiving positive feedback from
      program participants. CONCLUSION: Our results suggest that the following may be
      effective for further dissemination of the program: an explanation about the
      ripple effects of the program on family groups and obtaining assistance from the
      relevant organizational staff in consulting for funding of the program and
      referring program participants.

PMID- 24870146
TI  - Results of an intervention to support adolescents with developmental disabilities
      through cooperation between the school and community health services: the
      necessity for preventive measures for mental disorders in adolescents.

PMID- 24870145
TI  - Differences in PGE2 production between primary human monocytes and differentiated
      macrophages: role of IL-1beta and TRIF/IRF3.
AB  - Prostaglandin E2 (PGE2) is induced in vivo by bacterial products including TLR
      agonists. To determine whether PGE2 is induced directly or via IL-1beta, human
      monocytes and macrophages were cultured with LPS or with Pam3CSK4 in presence of
      caspase-1 inhibitor, ZVAD, or IL-1R antagonist, Kineret. TLR agonists induced
      PGE2 in macrophages exclusively via IL-1beta-independent mechanisms. In contrast,
      ZVAD and Kineret reduced PGE2 production in LPS-treated (but not in Pam3CSK4
      treated) monocytes, by 30-60%. Recombinant human IL-1beta augmented COX-2 and
      mPGES-1 mRNA and PGE2 production in LPS-pretreated monocytes but not in un-primed
      or Pam3CSK4-primed monocytes. This difference was explained by the finding that
      LPS but not Pam3CSK4 induced phosphorylation of IRF3 in monocytes suggesting
      activation of the TRIF signaling pathway. Knocking down TRIF, TRAM, or IRF3 genes
      by siRNA inhibited IL-1beta-induced COX-2 and mPGES-1 mRNA. Blocking of TLR4
      endocytosis during LPS priming prevented the increase in PGE2 production by
      exogenous IL-1beta. Our data showed that TLR2 agonists induce PGE2 in monocytes
      independently from IL-1beta. In the case of TLR4, IL-1beta augments PGE2
      production in LPS-primed monocytes (but not in macrophages) through a mechanism
      that requires TLR4 internalization and activation of the TRIF/IRF3 pathway. These
      findings suggest a key role for blood monocytes in the rapid onset of fever in
      animals and humans exposed to bacterial products and some novel adjuvants. 

PMID- 24870148
TI  - Food choice motives in male workers: a study using the laddering method.

PMID- 24870150
TI  - ATP-induced dimerization of the F0F1 epsilon subunit from Bacillus PS3: a
      hydrogen exchange-mass spectrometry study.
AB  - F0F1 ATP synthase harnesses a transmembrane electrochemical gradient for the
      production of ATP. When operated in reverse, this multiprotein complex catalyzes
      ATP hydrolysis. In bacteria, the epsilon subunit is involved in regulating this
      ATPase activity. Also, epsilon is essential for coupling ATP hydrolysis (or
      synthesis) to proton translocation. The epsilon subunit consists of a beta
      sandwich and two C-terminal helices, alpha1 and alpha2. The protein can switch
      from a compact fold to an alternate conformation where alpha1 and alpha2 are
      separated, resulting in an extended structure. epsilon from the thermophile
      Bacillus PS3 (Tepsilon) binds ATP with high affinity such that this protein may
      function as an intracellular ATP level sensor. ATP binding to isolated Tepsilon
      triggers a major conformational transition. Earlier data were interpreted in
      terms of an ATP + Tepsilonextended -> ATP.Tepsiloncompact transition that may
      mimic aspects of the regulatory switching within F0F1 (Yagi et al. (2007) Proc.
      Natl. Acad. Sci. U.S.A., 104, 11233-11238). In this work, we employ complementary
      biophysical techniques for examining the ATP-induced conformational switching of
      isolated Tepsilon. CD spectroscopy confirmed the occurrence of a large-scale
      conformational transition upon ATP binding, consistent with the formation of
      stable helical structure. Hydrogen/deuterium exchange (HDX) mass spectrometry
      revealed that this transition is accompanied by a pronounced stabilization in the
      vicinity of the ATP-binding pocket. Surprisingly, dramatic stabilization is also
      seen in the beta8-beta9 region, which is remote from the site of ATP interaction.
      Analytical ultracentrifugation uncovered a previously unrecognized feature of
      Tepsilon: a high propensity to undergo dimerization in the presence of ATP.
      Comparison with existing crystallography data strongly suggests that the
      unexpected beta8-beta9 HDX protection is due to newly formed protein-protein
      contacts. Hence, ATP binding to isolated Tepsilon proceeds according to 2ATP +
      2Tepsilonextended -> (ATP.Tepsiloncompact)2. Implications of this dimerization
      propensity for the possible role of Tepsilon as an antibiotic target are
      discussed.

PMID- 24870151
TI  - Advanced molecular self-assemblies facilitated by simple molecules.
AB  - Advanced materials are often based on smart molecular self-assemblies that either
      respond to external stimuli or have hierarchical structures. Approaches to this
      goal usually stem from complicated molecular design and difficult organic
      synthesis. In this invited feature article, we demonstrate that desired molecular
      self-assemblies can be made conveniently by introducing simple functional
      molecules into amphiphilic systems. We show that upon introducing specific small
      molecules which serve as responders, modulators, or even building blocks, smart
      supramolecular architectures can be achieved which avoid complicated organic
      synthesis. We expect that this could be a general and economical way to produce
      advanced materials in the near future. 

PMID- 24870149
TI  - Development of an activity-directed selection system enabled significant
      improvement of the carboxylation efficiency of Rubisco.
AB  - Photosynthetic CO(2) fixation is the ultimate source of organic carbon on earth
      and thus is essential for crop production and carbon sequestration. Ribulose-1,5
      bisphosphate carboxylase/oxygenase (Rubisco) catalyzes the first step of
      photosynthetic CO(2) fixation. However, the extreme low carboxylation efficiency
      of Rubisco makes it the most attractive target for improving photosynthetic
      efficiency. Extensive studies have focused on re-engineering a more efficient
      enzyme, but the effort has been impeded by the limited understanding of its
      structure-function relationships and the lack of an efficient selection system
      towards its activity. To address the unsuccessful molecular engineering of
      Rubisco, we developed an Escherichia coli-based activity-directed selection
      system which links the growth of host cell solely to the Rubisco activity
      therein. A Synechococcus sp. PCC7002 Rubisco mutant with E49V and D82G
      substitutions in the small subunit was selected from a total of 15,000 mutants by
      one round of evolution. This mutant showed an 85% increase in specific
      carboxylation activity and a 45% improvement in catalytic efficiency towards
      CO(2). The small-subunit E49V mutation was speculated to influence holoenzyme
      catalysis through interaction with the large-subunit Q225. This interaction is
      conserved among various Rubisco from higher plants and Chlamydomonas reinhardtii.
      Knowledge of these might provide clues for engineering Rubisco from higher
      plants, with the potential of increasing the crop yield.

PMID- 24870152
TI  - Encyrtidae (Hymenoptera: Chalcidoidea) from the Kingdom of Saudi Arabia.
AB  - This is the first major contribution to the fauna of the family Encyrtidae
      (Hymenoptera: Chalcidoidea) of the Kingdom of Saudi Arabia. The following new
      genus and 15 new species are described: Anagyrus azolus Hayat, sp. nov., A.
      raidahensis Hayat, sp. nov., Arabencyrtus qahtanii Hayat, gen. et sp. nov.,
      Cerchysiella arabia Hayat, sp. nov., C. azeeza Hayat, sp. nov., Cheiloneurus
      arabiacus Hayat, sp. nov., Leptomastidea abyad Hayat, sp. nov., Mahencyrtus
      asirensis Hayat, sp. nov., Metaphycus albidus Hayat, sp. nov., Microterys axonis
      Hayat, sp. nov., Neastymachus bolus Hayat, sp. nov., N. ceelus Hayat, sp. nov.,
      Ooencyrtus likinis Hayat, sp. nov., O. seronis Hayat, sp. nov., Zaomma astera
      Hayat, sp. nov. The following 27 genera are newly recorded from Saudi Arabia:
      Achalcerinys Girault, Aphycus Mayr, Apoleptomastix Kerrich, Callipteroma
      Motschulsky, Cerchysiella Girault, Cerchysius Westwood, Charitopus Foerster,
      Cheiloneurus Westwood, Coelopencyrtus Timberlake, Copidosoma Ratzeburg,
      Helegonatopus Perkins, Homalotylus Mayr, Lamennaisia Girault, Leptomastidea
      Mercet, Leptomastix Foerster, Mahencyrtus Masi, Mayridia Mercet, Microterys
      Thomson, Neastymachus Girault, Ooencyrtus Ashmead, Paraclausenia Hayat,
      Prionomastix Mayr, Prochiloneurus Silvestri, Rhopus Foerster, Syrphophagus
      Ashmead, Tyndarichus Howard, Zaomma Ashmead. The following 27 species are newly
      recorded from Saudi Arabia: Achalcerinys lindus (Mercet), Anagyrus gracilis
      (Hayat), A. shahidi Hayat, Aphycus secundus (Mercet), Apoleptomastix
      bicoloricornis (Girault), Callipteroma sexguttata Motschulsky, C. testacea
      Motschulsky, Cerchysius ugandensis Kerrich, Charitopus andalusicus Mercet,
      Cheiloneurus elegans (Dalman), C. quadricolor (Girault), Coelopencyrtus
      krishnamurtii (Mahdihassan), Comperiella aspidiotiphaga Subba Rao, Copidosoma
      floridanum (Ashmead), Habrolepis obscura Compere & Annecke, Helegonatopus
      formosus (Mercet), Homalotylus flaminius (Dalman), Lamennaisia ambigua (Nees), L.
      nobilis (Nees), Leptomastix dactylopii Howard, L. tsukumiensis Tachikawa,
      Mayridia pulchra Mercet, Paraclausenia herbicola Hayat, Prochiloneurus
      aegyptiacus (Mercet), P. pulchellus Silvestri, Rhopus nigroclavatus (Ashmead),
      Syrphophagus aphidivorus (Mayr). Eleven species belonging to the genera Anagyrus
      Howard, Charitopus, Helegonatopus, Mayridia, Metaphycus Mercet, Ooencyrtus,
      Prionomastix, Syrphophagus, and Tyndarichus, were not identified to species for
      the reasons given in the text. The known species treated in this paper, except
      for some well known species, are illustrated with suitable figures, and some
      species are either diagnosed or redescribed.  

PMID- 24870153
TI  - Biogeography and taxonomic status of Myotis keaysi pilosatibialis LaVal 1973
      (Chiroptera: Vespertilionidae) .
AB  - We document the first confirmed Colombian records of Myotis keaysi pilosatibialis
      LaVal, 1973 from various localities on the Colombian Caribbean and the Eastern
      Cordillera of the Colombian Andes. These records confirm geographic overlap
      between M. k. pilosatibialis and the nominate subspecies M. k. keaysi J. A.
      Allen, 1914, in northeastern Colombia, questioning the subspecific status of M.
      k. pilosatibialis. Models of potential distribution, produced for the two taxa by
      the application of the Maxent algorithm, show a potential geographic overlap in
      the northeastern portion of the Andes of Colombia and Venezuela. In order to
      clarify the taxonomic status of putative M. keaysi variants, we analyzed the
      variation of Colombian representatives of M. keaysi through a Principal
      Components Analysis (PCA), and a Discriminant Function Analysis (DFA) performed
      on 18 cranio-dental measurements, as well as the analysis of discrete characters.
      The morphological independence between M. k. keaysi and M. k. pilosatibialis was
      supported statistically in our PCA and DFA, as well as by the presence of unique
      discrete characters, lending support to the recognition of M. k. pilosatibialis
      as full species. Herein, we include new discrete characters setting apart M.
      pilosatibialis from the morphologically similar species M. keaysi.  

PMID- 24870154
TI  - The genus Zambedania Mahunka 1972 (Acari: Heterostigmatina: Pygmephoridae)
      redescription of the type species Z. africana and descriptions of two new species
      from Africa and South America.
AB  - The type species of the genus Zambedania Mahunka, 1972 (Z. africana Mahunka,
      1972) is redescribed based on the holotype collected from soil in Zimbabwe. Two
      new species are described and illustrated herewith: Z. madagascariana from
      Madagascar and Z. argentiniana from Argentina. The generic diagnosis of
      Zambedania is amended, and the key to its species is supplied. Morphology,
      taxonomy and biology of included species are briefly discussed. The first record
      of the genus being phoretic on a South American nemesiid spider is presented. 

PMID- 24870155
TI  - A new lizard of the Phymaturus genus (Squamata: Liolaemidae) from Sierra Grande,
      northeastern Patagonia, Argentina.
AB  - A new species of lizard of the saxicolous and viviparous genus Phymaturus from
      Patagonia is described. The new species is a member of the Phymaturus patagonicus
      species group distributed on volcanic plateaus, mountains or rocky outcrops of
      southern Argentina. Phymaturus yachanana sp. nov. differs from the other members
      of the patagonicus group by a dorsal pattern of small and medium-sized white
      spots on a brown background, the number of scales around the midbody, genetic
      differences in mitochondrial and nuclear markers, and allopatric geographic
      distribution in an isolated group of hills. As other species of the group, the
      new species is viviparous and herbivorous.  

PMID- 24870156
TI  - A new species of Pinnixa (Crustacea: Decapoda: Brachyura: Pinnotheridae)
      associated with a tube worm, Chaetopterus cautus (Annelida: Polychaeta), from
      Tokyo Bay, Japan.
AB  - A new species of the pea crab genus Pinnixa White, 1846 (Pinnotheridae), P. banzu
      n. sp., is described and illustrated on the basis of four specimens from Banzu,
      an estuary of the Obitsu River, Kisarazu, Chiba Prefecture, Japan. All the
      specimens examined were associated with the polychaete tube worm Chaetopterus
      cautus Marenzeller, 1879 (Chaetopteridae). The new species is very similar to P.
      chaetopterana Stimpson, 1860 from the western Atlantic, P. occidentalis Rathbun,
      1894 from northwest North America, and P. rathbuni Sakai, 1934 from East Asia. It
      is distinguished from the latter three species by characters of the carapace,
      ambulatory legs, male abdomen, and male first gonopod. It is suggested that
      previous records reporting on the association of P. rathbuni with Chaetopterus
      tube worms might be actually referred to the new species. 

PMID- 24870157
TI  - Eviota brahmi n. sp. from Papua New Guinea, with a redescription of Eviota
      nigriventris (Teleostei: Gobiidae).
AB  - Greenfield & Randall (2011) described the gobiid fishes Eviota dorsogilva from
      Fiji and E. dorsopurpurea from Papua New Guinea as new species in what they
      termed the Eviota nigriventris complex. They also extended the range of E.
      nigriventris, type locality Banda Sea, to Milne Bay, Papua New Guinea. In the
      present paper, we describe their misidentified E. nigriventris from Papua New
      Guinea as a new species, E. brahmi, and redescribe E. nigriventris based on new
      material from near the type locality. The four species of this complex differ
      mainly in coloration, but are also shown to be distinct using mitochondrial and
      nuclear DNA. 

PMID- 24870158
TI  - Two new species of Seira Lubbock (Collembola, Entomobryidae, Seirini) from South
      Brazil.
AB  - Two new species of Seira, Seira tinguira sp. nov. and Seira paulae sp. nov. from
      Atlantic Rainforest Phytogeographic Domain in Parana State, southern Brazil, are
      described and illustrated, with dorsal chaetotaxy labeled in detail. The general
      morphology of S. tinguira sp. nov. resembles S. frater (Bonet) and S. oceanica
      Yosii, however differs by chaeta Pa4 present in head, three extra macrochaetae
      (m1i2, p1i2 and one extranumerary) in mesothorax; four (a3, p2e, p2ea and a4) in
      metathorax; one (m3ep) in the second abdominal segment , among other
      morphological features. Seira paulae sp. nov. is similar to S. atrolutea (Arle)
      in body colour, however dorsal chaetoxy resembles S. mendoncea Bellini &
      Zeppelini and S. ritae Bellini & Zeppelini. On the other hand, the new species
      clearly differs from other similar taxa by the presence of cephalic macrochaeta
      M2; three macrochaetae (M2, M1 and M2i) in mesothorax and p2p as microchaeta; one
      extra macrochaeta (p1i) in metathorax and two (a1 and p2ea) as macro or
      microchaetae; macrochaeta m3ep missing in the second abdominal segment;
      macrochaeta am6 present in the third abdominal segment among other features.
      Seira tinguira sp. nov. was found in different habitats of Parana State while S.
      paulae sp. nov. was recorded only in its type locality. A distribution map is
      provided for both species. With the presented description there are now four
      recorded species of Seira from south Brazil. 

PMID- 24870159
TI  - The status of Leptopelis barbouri Ahl, 1929 and eleven other nomina of the
      current tree-frog genus Leptopelis (Arthroleptidae) described from East Africa,
      with a redescription of Leptopelis grandiceps Ahl, 1929.
AB  - An investigation of name-bearing types and other relevant type specimens of
      twelve nominal Leptopelis taxa described from or distributed in the Eastern Arc
      Mountains in East Africa was carried out. Our aim was to clarify their status and
      where necessary revise respective nomina. We suggest several nomenclatural and
      taxonomic actions: 1) Leptopelis barbouri Ahl, 1929 is transferred to the
      synonymy of Leptopelis flavomaculatus (Gunther, 1864) as a junior subjective
      synonym; 2) Leptopelis grandiceps Ahl, 1929 is resurrected from the synonymy of
      Leptopelis uluguruensis Barbour & Loveridge, 1928 as a valid species conforming
      to the tree frogs which have been known as 'L. barbouri' and a lectotype is
      designated; 3) Leptopelis usambarae Ahl, 1929 is transferred from the synonymy of
      L. uluguruensis Barbour & Loveridge, 1928 to the synonymy of L. grandiceps Ahl,
      1929 as a subjective synonym; 4) a lectotype of Leptopelis amaniensis Ahl, 1929
      (synonym of L. uluguruensis), Hylambates johnstoni Boulenger, 1897 (synonym of L.
      flavomaculatus) and Leptopelis signifer Ahl, 1929 (synonym of L. vermiculatus) is
      designated to stabilize identity of the nomina; and 5) the type locality of
      Leptopelis martiensseni Ahl, 1929 and Leptopelis tanganus Ahl, 1929 is corrected.

PMID- 24870160
TI  - The millipede genus Riukiaria Attems, 1938 in continental China, with
      descriptions of new species (Diplopoda: Polydesmida: Xystodesmidae).
AB  - Fresh collections of Diplopoda from China contain five new species of the large,
      East Asian, warm temperate to subtropical genus Riukiaria: R. martensi sp. nov.,
      from Shaanxi Province, as well as R. belousovi sp. nov., R. kabaki sp. nov., R.
      korolevi sp. nov. and R. davidiani sp. nov. from Sichuan Province. A key is given
      to all eight Riukiaria species currently known to occur in mainland China,
      including R. tianmu (Tanabe, Ishii & Yin, 1996), comb. nov. ex Sinoria Tanabe,
      Ishii & Yin, 1996, the latter genus a new junior subjective synonym of Riukiaria,
      syn. nov. 

PMID- 24870161
TI  - The man who loved flies: a biographical profile of Nelson Papavero .
AB  - Nelson Papavero is one of the major Brazilian zoologists. His contribution to the
      field began in the second half of the twentieth century, when he started
      publishing in the areas of entomology, systematics, biogeography, and history of
      science, while working at graduate courses and training teachers and students.
      Papavero was one of the earliest Brazilian advocates of Hennig's phylogenetic
      systematics. In his entomological work, his first widely recognised works were
      the Catalogue of South American Diptera and his essays on the history of
      Neotropical Dipterology. Papavero's greatest contribution however, is in his
      Special Courses on Zoological Systematics, as well as his numerous administrative
      positions during his academic career. All these were fundamental to the
      development of zoology and comparative biology in Brazil and other Latin American
      countries. Here we present a biography of Nelson Papavero, along with several
      personal anecdotes, and his role in the development of Brazilian biological
      systematics over the last 50 years.  

PMID- 24870162
TI  - Two new species and three new records of the genus Aphelocheirus (Hemiptera:
      Heteroptera: Aphelocheiridae) from China.
AB  - Two new species of the genus Aphelocheirus (Hemiptera: Heteroptera:
      Aphelocheiridae), A. longlingensis sp. nov. from Yunnan and A. motuoensis sp.
      nov. from Xizang (Tibet) Autonomous Region are described in this paper. A.
      similaris Polhemus & Polhemus, 1989, A. nawae Nawa, 1905 and A. tuberculipes
      Zettel & Tran, 2009 are reported from China for the first time. A key to Chinese
      species of Aphelocheirus is given. Dorsal habitus photographs of the species are
      provided, accompanied by illustrations of male genitalic structures, inner
      projection and female ventral aspect of posterior abdominal segments.  

PMID- 24870163
TI  - Revision of the Neotropical burrowing water beetle genus Liocanthydrus Guignot
      (Coleoptera: Noteridae: Noterinae: Noterini) with the description of two new
      species.
AB  - The burrowing water beetle genus Liocanthydrus Guignot, 1957 is redefined and its
      species are revised. Of the four current species, three are recognized as
      belonging to the genus and redescribed: L. angustus (Guignot, 1957), L.
      octoguttatus (Zimmermann, 1921) and L. uniformis (Zimmermann, 1921). The fourth
      species, L. buqueti (Laporte, 1835) is found to not be a member of Liocanthydrus,
      but of an undescribed genus. The noterid genus Siolius J. Balfour-Browne, 1969,
      is synonymized with Liocanthydrus (new synonymy) based on comparison of type
      specimens in both groups. Two of the three species described in Siolius, S.
      bicolor J. Balfour-Browne, 1969 and S. clayae J. Balfour-Browne, 1969, are
      recognized as valid, transferred to Liocanthydrus, and redescribed. The third, S.
      amazonicus J. Balfour- Browne, 1969, is synonymized with L. uniformis (new
      synonymy). Two new species from South America, L. armulatus sp. n. and L. nanops
      sp. n. are also recognized and described. A lectotype is designated for
      Canthydrus octoguttatus Zimmermann, 1921. After this revision, there are seven
      valid species of Liocanthydrus. Habitus photos are provided, diagnostic
      characters of all recognized species are illustrated, distributions are provided,
      and a key to the species is included. 

PMID- 24870164
TI  - A new genus and species of Schizogyniidae (Acari: Mesostigmata) associated with
      carabid beetles (Coleoptera: Carabidae) from Ukraine.
AB  - A new genus and species of Schizogyniidae (Acari: Mesostigmata: Celaenopsoidea),
      Euroschizogynium calvum gen. nov. and sp. nov., associated with Scarites
      terricola Bonelli, 1813 (Coleoptera: Carabidae) is described from Ukraine,
      representing the first record of the family from the Palaearctic. Fusura civica
      Valle & Fox, 1966 is moved out of the Schizogyniidae and placed into the
      Megacelaenopsidae. A new diagnosis for the family Schizogyniidae and a key to
      genera are provided. 

PMID- 24870165
TI  - Albistyla, a new genus of Neotropical Limosininae (Diptera: Sphaeroceridae) .
AB  - The genus Albistyla is described for a group of similar, highly distinctive
      Neotropical species that key out at couplet 55 of the key to Neotropical
      Sphaeroceridae in Marshall and Buck (2010). Albistyla is diagnosed by the
      combination of a single pair of strongly cruciate interfrontal bristles, two
      dorsocentral bristles, and the costa ending at the tip of R4+5. It is defined as
      a monophyletic group primarily on the basis of the unusually modified male
      sternite 5 and the distinctive white surstylus with broad apical scales. The
      genus is infrequently collected and only the type species is known from good
      series. Many of the specimens examined were taken in association with tree falls
      or similar habitats rich in green leaf litter.

PMID- 24870166
TI  - Psilorhynchus khopai, a new fish species (Teleostei: Psilorhynchidae) from
      Mizoram, northeastern India.
AB  - Psilorhynchus khopai, a new species of Psilorhynchidae, is described from Tuisi
      River, a tributary of Kaladan River, in Mizoram, India. The species is proposed
      to be a member of the Psilorhynchus homaloptera species group and can be
      distinguished from its congeners in having a forked caudal-fin with 9 + 9
      principal caudal rays, 14-17 predorsal scale rows, 39-41 lateral-line scale rows,
      mid-lateral body with 9-12 indistinct small dark brown round markings forming a
      lateral stripe and, in life, a faint gold stripe along dorsal midline with 4-5
      black spots between dorsal fin and caudal fin base. 

PMID- 24870167
TI  - Two new species of Haliclona Grant, 1836 (Haplosclerida: Chalinidae) from Sergipe
      State, Brazil.
AB  - Haliclona is one of the most species-rich genera among Demospongiae, but with
      only 11 species recorded for the Brazilian coast. Here we describe two new
      species of Haliclona collected by trawling at Sergipe State (Northeastern
      Brazil). Haliclona (Halichoclona) dura sp. nov. is distinguished by the
      combination of confused choanosome with dense reticulation, oxeas with stepped
      and mucronate points, color dark brown externally and light beige internally,
      consistency firm and incompressible. Haliclona (Soestella) brassica sp. nov. is
      set apart by the combination of a choanosomal skeleton with rounded meshes,
      strongyles, raphides, color beige and consistency soft. 

PMID- 24870168
TI  - Third instars larvae of Gepus gibbosus Holzel, 1968 (Neuroptera:
      Myrmeleontindae).
AB  - The third instar larva of Gepus gibbosus Holzel, 1968 are described and figured
      for the first time using light and scanning electron microscopy. The females were
      collected from Derik, Mardin Province, Turkey and maintained in the laboratory.
      The morphology of different parts of the larva such as head, mandibles, and
      antennae are described and illustrated. G. gibbosus is new for the Turkish fauna.

PMID- 24870169
TI  - One new genus and two new species of the tribe Meconematini (Orthoptera:
      Tettigoniidae: Meconematinae) from Yunnan, China.
AB  - One new genus, Paraphlugiolopsis Bian & Shi gen. nov., and two new species,
      Paraphlugiolopsis jiangi Bian & Shi sp. nov. and Paraphlugiolopsis lobocera Bian
      & Shi sp. nov., are described in the tribe Meconematini. The two new species have
      similar habitat in Yunnan, China, but live in different altitudes. All material
      examined is deposited in the Museum of Hebei University. 

PMID- 24870170
TI  - Description of a new species of Aegosoma Audinet-Serville, 1832 from Vietnam
      (Coleoptera: Cerambycidae: Prioninae) .

PMID- 24870171
TI  - A new species of Afroarabiella Yakovlev, 2008 (Lepidoptera, Cossidae) from the
      Republic of South Africa, including a world catalogue of the genus.
AB  - The genus Afroarabiella Yakovlev, 2008 (Lepidoptera: Cossidae) was established
      for Cossus tahamae Wiltshire, 1949 by Yakovlev (2008). Currently, seven species
      are included in the genus (Yakovlev 2008). Yakovlev (2011) added an additional
      new species, A. tanzaniae Yakovlev from Tanzania. Members of the genus are
      widespread from the southwestern Arabian Peninsula and throughout much of Africa
      (Fig. 1). During the studies of Lepidoptera by Petr Ustjuzhanin (Novosibirsk,
      Russia) and Vasilij Kovtunovich (Moscow), a new species of the genus
      Afroarabiella was discovered and the  description is given below.  

PMID- 24870172
TI  - A review of the genus Pempheris (Perciformes, Pempheridae) of the Red Sea, with
      description of a new species.
AB  - Four species of the fish genus Pempheris are recognized for the Red Sea: P.
      adusta Bleeker, 1877; P. mangula Cuvier, 1829; P. nesogallica Cuvier in Cuvier &
      Valenciennes, 1831; and a new species P. tominagai. All are wide-ranging in the
      western Indian Ocean, and P. mangula has migrated via the Suez Canal to the
      eastern Mediterranean Sea. Morphological and genetic analysis of 15 species in
      this genus show that P. adusta, a widely distributed species, that can't be
      divided into different species, because of the continuity of morphologies and
      distribution, and lack of variance in genetics between Indian Ocean, Red Sea, and
      Pacific Ocean populations. This confirms that the two subspecies described by
      Randall et al. (2013) are both synonyms of P. adusta. Pempheris adusta is
      distinguished from other species by a blackish spot on pectoral fin base, pored
      lateral-line scales 56-64, scale rows above lateral line 4 1/2-6 1/2, distinct
      blackish band on outer edge of anal fin, and blackish band on posterior edge of
      caudal fin. Pempheris mangula was named by Cuvier (1829) in a footnote making
      reference to a drawing and short description in Russell (1803) of a Pempheris
      from southeast India, giving only the native name ''Mangula-Kutti'', and listing
      no specimen. The wide distribution of this species, from the Indian Ocean to the
      Red Sea is also demonstrated by morphological and genetic analysis. Thus, the
      specimen collected from southern India is herein designated as the neotype. This
      species is distinguished from other species by its huge eye, deep body, blackish
      tip of the dorsal fin, pored lateral-line scales 49-60, and scale rows above
      lateral line 4 1/2-5 1/2. The extant syntype of Kossmann & Rauber's P. rhomboidea
      is designated as the lectotype of the species; however, P. rhomboidea is a
      synonym of P. mangula. In addition, Kossmann & Rauber's Pempheris erythraea and
      P. russellii Day, 1888 are also synonyms of P. mangula. Of two existing syntypes
      of P. nesogallica from Mauritius, one is designated as the lectotype, the other
      is re-identified as P. mangula; P. nesogallica is presently known only from the
      southern Red Sea. This species has a similar morphology to P. mangula, but can be
      distinguished by a smaller eye than P. mangula, and lack irregular faint
      longitudinal light stripes on the body side. Pempheris tominagai are
      distinguished from P. schwenkii Bleeker 1855, formerly misidentified, by the form
      of posterior nostril, scale counts, color of caudal fin, and by a 2.1%
      mitochondrial DNA sequence divergence.  

PMID- 24870173
TI  - Four new species of pholcine spiders (Araneae: Pholcidae) from Southeast Asia.
AB  - Four new species belonging to four genera of the subfamily Pholcinae are reported
      from Southeast Asia: Belisana protumida spec. nov. (male, female), Khorata bayeri
      spec. nov. (male), Pholcus schawalleri spec. nov. (male), and Uthina khaosokensis
      spec. nov. (male). 

PMID- 24870174
TI  - Studies of Madagascan Ptiliidae (Coleoptera) 2: the genus Ptenidium including
      three new species .
AB  - This is the second report detailing Ptiliidae collected from forest leaf litter
      by the Moravian Museum expeditions to Madagascar 2010-2012. 3 new species are
      described and figured: Ptenidium azafady sp. n., P. lambdai sp. n., and P.
      tanalai sp.n., and the criteria for assessing subgeneric status discussed. 

PMID- 24870175
TI  - Taxonomic review of the genus Spatulignatha Gozmany, 1978 (Lepidoptera:
      Lecithocerinae), with descriptions of two new species in China.
AB  - The genus Spatulignatha Gozmany is reviewed. Two new species are described based
      on the Chinese material: S. arcuata sp. nov. from Guangdong, Hunan and Yunnan,
      and S. longizonalis sp. nov. from Guangxi. The female genitalia of S. hemichrysa
      (Meyrick, 1910) and the female of S. idiogena Wu, 1994 are described for the
      first time, and the previously described female of S. hemichrysa by Gozmany
      (1978) is considered to be the female of S. olaxana Wu, 1994. Images of adults
      and genitalia are provided. 

PMID- 24870176
TI  - A new species of Sphaeronemoura (Plecoptera: Nemouridae) from Henan Province of
      China, with additions to generic characters of the female and larva.
AB  - A new species of the genus Sphaeronemoura (Plecoptera: Nemouridae:
      Amphinemurinae), S. separata sp. n. is described from the male, female, and
      larvae collected in Henan Province of China. The internal genitalia of the female
      adult is described for the first time for the genus, and additional generic
      characters for the larva are also given. The known distributions of all
      Sphaeronemoura species is presented. 

PMID- 24870177
TI  - Stenorynchoacrum xijiangensis, a new genus and a new species of Labeoninae fish
      from Guangxi, China (Teleostei: Cyprinidae.
AB  - Stenorynchoacrum xijiangensis, a new genus and a new species of Cyprinidae, is
      described from a tributary of the Zhujiang River (Pearl River) in Guangxi
      Province, China. It can be distinguished from other genera of Labeoninae by the
      following characters: middle part of rostral cap undeveloped, narrow, only
      covering the base of the upper jaw, both sides of rostral cap well developed and
      extending upward, rostral cap connected the lower lip with free lateral margin,
      the median part of lower lip protruded to form a round fleshy pad, whose
      posterior margin continuous with the mental region. 

PMID- 24870178
TI  - Notes on the genus Napialus Chu & Wang (Lepidoptera: Hepialidae), with
      description of a new species from China.
AB  - Napialus spinosus Li & Wei, sp. nov. is described as new based on a male specimen
      collected in Jiangxi Province of China. Image of the adult, illustrations of the
      antenna, venation, and eighth abdomeninal segment as well as male genitalia are
      presented. A species checklist and key to the species of Napialus are provided
      and the known distribution of each species is mapped with respect to temperature
      gradients.

PMID- 24870179
TI  - Dina sketi n. sp., a new erpobdellid leech (Hirudinida: Erpobdellidae) from
      Bosnia and Herzegovina.

PMID- 24870180
TI  - Further notes on South American species of Baetidae (Ephemeroptera) assigned to
      Moribaetis Waltz & McCafferty, 1985.
AB  - The types of the remaining two South American species classified in Moribaetis
      Waltz & McCafferty, 1985 were studied. Moribaetis comes (Navas, 1912) is
      designated as a nomen dubium based on the lack of information in the original
      description, the damaged type and the resultant improbability of assigning
      specimens to this species. The type-material of M. aneto (Traver, 1971), on the
      other hand, is well-preserved. Based on the morphology of males and females, we
      propose a new combination, Camelobaetidius aneto. In conclusion, we consider the
      genus Moribaetis to be absent from South America. 

PMID- 24870181
TI  - The syrphids of Serra do Courel, Northern Spain and description of a new
      Cheilosia Meigen species (Diptera: Syrphidae).
AB  - The syrphids (Syrphidae) of Serra do Courel, a mountainous locality of just over
      20,000ha at the west end of the Cantabrian Mountains, northern Spain are poorly
      known. The Scottish based, Malloch Society visited the locality in May 2012 and
      collected a total of 462 specimens of 98 syrphid species and 36 genera. These
      represent the first syrphid records from Serra do Courel. The area has many
      meadows and small woodlands or 'soutos' and these habitats combined were the most
      productive, 69 spp. recorded. Cheilosia lucense Ricarte sp. nov. is described
      from Courel and compared with other species of the alpina group. Six other
      syrphid species were new to the Iberian Peninsula, three of which belong to the
      saproxylic genus, Brachyopa. In common with studies elsewhere in the Cantabrian
      Mountains, Cheilosia was the most diverse genus and 21 species were recorded. The
      syrphid fauna of the Cantabrian Mountains includes 203 species of which 24 are
      here added and a species checklist provided.  

PMID- 24870182
TI  - Revision of the Embolemidae of Japan (Hymenoptera: Chrysidoidea), with
      description of a new genus and two new species.
AB  - Seven species of Embolemidae are recognized in Japan. They belong to two genera:
      Embolemus Westwood 1833 and Trogloembolemus Olmi, Mita et Guglielmino, gen. nov.
      (type species T. fujiei Olmi, Mita et Guglielmino, sp. nov.) Embolemus
      honshuensis Olmi, Mita et Guglielmino, sp. nov. (Japan, Honshu) and
      Trogloembolemus fujiei Olmi, Mita & Guglielmino, sp. nov. (Japan, Honshu) are
      described and figured. A key to the genera and species of Japan is presented.
      Trogloembolemus fujiei sp. nov., collected in the soil at a depth of two metres
      and almost blind, is the first species of Embolemidae with troglobitic habitus.  

PMID- 24870183
TI  - A new species of predaceous mite of the genus Neoseiulus Hughes (Acari,
      Phytoseiidae), with redescriptions of N. magnanalis (Thor) and N. ellesmerei
      (Chant & Hansell), from Svalbard, High Arctic.
AB  - A new species of phytoseiid mite of the genus Neoseiulus (Acari, Phytoseiidae)
      found in Svalbard is described and illustrated. Redescriptions, drawings,
      measurements, and diagnosis of two related species, N. magnanalis (Thor) and N.
      ellesmerei (Chant & Hansell) are given. A neotype is designated for N.
      magnanalis. 

PMID- 24870184
TI  - A new species of Didogobius (Teleostei: Gobiidae) from the Canary Islands.
AB  - Didogobius helenae is described from the Canary Islands. It has a sensory
      papillae pattern that is consistent with the current diagnosis for Didogobius,
      but lacks all head canals and pores that are present in other members of the
      genus. Pores, in general, are replaced by large papillae.  The species is defined
      by first dorsal fin VI; second dorsal fin I,10; anal fin I,9; pectoral fin 16-17;
      pelvic fin I,5 and disk shaped; lateral scales 28-30, cycloid at anterior,
      becoming ctenoid posteriorly; cycloid scales present on belly and posterior
      breast; predorsal region, cheek, operculum and base of pectoral fin without
      scales; lower most scale on the caudal fin-base with elongate, thickened ctenii
      along the upper and lower posterior edges. Color in life consists of four
      mottled, wide brown-orange bars separated by narrower white bars on the trunk,
      the cheek whitish with 5 more or less circular blotches of orange, outlined in
      dark brown and a black spot on ventral operculum. A key to the species is
      provided.  

PMID- 24870185
TI  - Revision of the subgenus Diphaomyia Vargas of Culicoides Latreille from India
      with description of a new species (Diptera: Ceratopogonidae).
AB  - Indian species of Culicoides Latreille, subgenus Diphaomyia Vargas are revised.
      The Clavipalpis group sensu Wirth & Hubert is transferred to the subgenus
      Diphaomyia with revised diagnoses of the subgenus and species groups. One
      species, C. peculiaris has been removed from the subgenus Diphaomyia, the
      remaining species are freshly reviewed with description of a new one, Culicoides
      (Diphaomyia) soleamaculatus sp. n. A key to the Indian species of Diphaomyia is
      presented here. 

PMID- 24870186
TI  - Studies in Mexican Grasshoppers: Liladownsia fraile, a new genus and species of
      Dactylotini (Acrididae: Melanoplinae) and an updated molecular phylogeny of
      Melanoplinae.
AB  - Liladownsia fraile gen. nov. sp. nov. Fontana, Marino-Perez, Woller & Song (Lila
      Downs' friar grasshopper) of the tribe Dactylotini (Orthoptera: Acrididae:
      Melanoplinae) is described from the pine-oak forest of the Sierra Madre del Sur
      Mountain Range in Oaxaca, Mexico. Taxonomic placement of this new genus is
      justified based on morphological characters as well as a molecular phylogeny.
      Information about the probable host plant, phenology, and known localities is
      also presented. We also present an updated molecular phylogeny of Melanoplinae,
      which includes representatives of five of the seven recognized tribes. The
      monophyly of the subfamily and the included tribes is tested and we find
      Dactylotini to be paraphyletic because of the placement of Hesperotettix Scudder,
      1876. We also recover strong close relationships between the new genus and
      Perixerus Gerstaecker, 1873 and Dactylotum Charpentier, 1845.   

PMID- 24870187
TI  - Asprothrips bimaculatus sp.n. (Thripidae, Dendrothripinae) from Martinique.
AB  - Asprothrips bimaculatus sp. n. is described from Martinique. It is unique among
      the five species now recognised in this genus in having the body sharply
      bicoloured, with the head and thorax dark but the abdomen white. 

PMID- 24870188
TI  - Gobduntaulepis, a new generic name for Acantholepis Pianovskij, 1989 (Conodonta)
      non Kroyer, 1846 (Actinopterygii).

PMID- 24870189
TI  - Revision of Trachelissa Aurivillius, 1912 (Insecta: Coleoptera: Cerambycidae).
AB  - A revision of the genus Trachelissa Aurivillius, 1912, based on a study of
      external morphology and terminalia, is presented. The genus and its species are
      redescribed. Five species are recognized, two of which are described as new: T.
      bella sp. nov. from Bolivia and T. opaca sp. nov. from Argentina. A new host
      plant for T. maculicollis Audinet-Serville, 1834 is recorded. A key to all
      species, and their photographs and distribution maps are provided.  

PMID- 24870190
TI  - New additions to the genus Kisaura Ross (Trichoptera: Philopotamidae) from the
      Indian Himalaya.
AB  - Four new species of genus Kisaura Ross are added to the philopotamid fauna of
      India. The newly described species are K. holiensis sp. nov., K. holzenthali sp.
      nov., K. morsei sp. nov. (all from Uttarakhand) and K. golitarensis sp. nov. from
      Sikkim. 

PMID- 24870191
TI  - Transisthmian differentiation in the tree-climbing mangrove crab Aratus H. Milne
      Edwards, 1853 (Crustacea, Brachyura, Sesarmidae), with description of a new
      species from the tropical eastern Pacific.
AB  - The tree-climbing mangrove crab Aratus pisonii (H. Milne Edwards, 1837)
      (Brachyura, Sesarmidae) is considered to have a transisthmian distribution, due
      to its presence in mangroves of the Western Atlantic as well as the Eastern
      Pacific. We here present evidence, based on the morphologies of male gonopods and
      on genetic data, that populations from these two coastlines are morphologically
      and genetically distinct and require the description of a new species, Aratus
      pacificus n. sp., as the sister-species of Aratus pisonii. The corresponding
      speciation event can be regarded as the outcome of differentiation following the
      closure of the Isthmus of Panama. As these coastal brackish species were probably
      among the last ones to become separated, the speciation can thus be dated to a
      time frame of no more than 3.1 million years. 

PMID- 24870192
TI  - Atrocalopteryx auco spec. nov. from Vietnam, with taxonomic notes on its
      congeners (Odonata: Calopterygidae).
AB  - Atrocalopteryx auco Hamalainen, spec. nov. (holotype ?, from Vietnam, Lang Son
      province, Huu Lien, Tan Lai, alt. 260 m, 9 June 2008, deposited at RMNH, Leiden,
      The Netherlands) is described and illustrated for both sexes and compared with
      other species in the genus. The new combination Atrocalopteryx laosica (Fraser,
      1933), comb. nov. is made. An annotated list of Atrocalopteryx species and keys
      to both sexes are presented. Male of A. auco differs from the other two
      completely opaque-winged species (A. atrata and A. atrocyana) by having yellowish
      crossveins on the under surface of the wings and by having the underside of
      abdominal segments 8-10 strikingly yellowish. The female of A. auco can be easily
      separated from A. atrata  and A. atrocyana  by the presence of whitish
      pseudopterostigma in both wings. Problems in the definition of the genus
      Atrocalopteryx are discussed. 

PMID- 24870193
TI  - Review of the Gasteruptiidae (Hymenoptera: Evanioidea) from the territory of the
      former Yugoslavia, with three newly reported species.
AB  - The results of more than 120 years of investigation of the fauna of
      Gasteruptiidae for the territory of former Yugoslavia (including Bosnia and
      Herzegovina, Croatia, FYR of Macedonia, Montenegro, Serbia and Slovenia) are
      summarized. Results from recently collected material and from unidentified
      specimens in collections are combined with those of published records. The total
      number of valid species of the genus Gasteruption Latreille for the area of
      former Yugoslavia is 22, which is more than in any country represented in Fauna
      Europaea database. One species is firstly recorded for the mainland Europe (G.
      syriacum Szepligeti), two more species are newly recorded for the investigated
      area and there are 23 first country-records for the involved countries (based on
      17 species). 

PMID- 24870194
TI  - A new species of crinoid-associated Periclimenes from Honduras (Crustacea:
      Decapoda: Palaemonidae).
AB  - A new species of crinoid associated Periclimenes, P. rincewindi sp. nov. is
      described from the Bay Islands (Honduras) in the Caribbean. The species
      associates with the swimming crinoid, Analcidometra armata and displays a unique
      colour pattern. Morphologically, the new species is closely related to the other
      known crinoid associates in the Caribbean, specifically Periclimenes crinoidalis,
      from which it can be distinguished by a suite of relatively minor morphological
      features. 

PMID- 24870195
TI  - Cochabambia Piran, 1959 (Hemiptera: Heteroptera: Acanthosomatidae), a senior
      homonym of Cochabambia Marcuzzi, 1985 (Coleoptera: Tenebrionidae), with notes on
      the placement of Cochabambia Piran.
AB  - Cochabambia Marcuzzi (1985) (Coleoptera: Tenebrionidae) is a junior homonym of
      Cochabambia Piran, 1959 (Hemiptera: Heteroptera: Acanthosomatidae).
      Allotriocochabambia is proposed as a new name for the tenebrionid genus, and as
      result Allotriocochabambia kulzeri (1985) is proposed as new combination. The
      placement of Cochabambia Piran within the Acanthosomatidae is discussed.  

PMID- 24870196
TI  - First record of the genus Cladonema (medusae and polyps) in Colombia.

PMID- 24870198
TI  - Floating-bioadhesive gastroretentive Caesalpinia pulcherrima-based beads of
      amoxicillin trihydrate for Helicobacter pylori eradication.
AB  - CONTEXT: An oral dosage form containing floating bioadhesive gastroretentive
      microspheres forms a stomach-specific drug delivery system for the treatment of
      Helicobacter pylori. OBJECTIVES: To prepare and evaluate controlled release
      floating bioadhesive gastroretentive chitosan-coated amoxicillin trihydrate
      loaded Caesalpinia pulcherrima galactomannan (CPG)-alginate beads (CCA-CPG-A),
      for H. pylori eradication. MATERIALS AND METHODS: CCA-CPG-A beads were prepared
      by ionotropic gelation, using 2(3) factorial design with quantity of drug,
      combination of CPG with sodium alginate and concentration of calcium chloride as
      variables. Beads facilitated mucoadhesion to gastric mucosa with floating nature
      caused by chitosan coating for wide distribution throughout GIT. Developed beads
      were evaluated for characteristics like beads size-morphology, entrapment
      efficiency, DSC, XRD, FTIR, swelling ratio, in vitro mucoadhesion, in vitro drug
      release, in vitro floating and in vitro H. pylori growth inhibition studies. CCA
      CPG-A beads were studied in Wistar rats for in vivo gastric mucoadhesion, in vivo
      H. pylori growth inhibition studies using PCR amplification of isolated DNA,
      rapid urease test. RESULT: Developed beads possess drug release of 79-92%,
      entrapment efficiency of 65-89%, mucoadhesion of 61-89%. In vivo mucoadhesion
      study showed more than 85% mucoadhesion of beads even after 7th hour. In vitro-in
      vivo growth inhibition study showed complete eradication of H. pylori.
      DISCUSSION: CPG-alginate and chitosan in beads interacts with gastric
      mucosubstrate surface for prolonged gastric residence with floating bioadhesion
      mechanism for H. pylori eradication in rats. CONCLUSION: Floating bioadhesive CCA
      CPG-A beads offer a promising drug delivery system for H. pylori eradication at
      lower dose, reduced adverse effect and enhance bioavailability.

PMID- 24870199
TI  - The mechanism for increasing the oral bioavailability of poorly water-soluble
      drugs using uniform mesoporous carbon spheres as a carrier.
AB  - Uniform mesoporous carbon spheres (UMCS) were used as a carrier to improve the
      bioavailability of the model drug, celecoxib (CEL). Furthermore, we investigated
      the mechanism responsible for the improved bioavailability of CEL. The
      association, adhesion and uptake of UMCS by intestinal epithelial cells were
      studied by transmission electron microscopy (TEM), fluorescence-activated cell
      sorting (FACS) and laser confocal scanning microscopy (LCSM). UMCS was found to
      promote cellular uptake of CEL. Drug transport in Caco-2 cell monolayers proved
      that UMCS can significantly reduce the rate of drug efflux and improve CEL
      permeability. The dissolution rate of CEL from drug-loaded samples was markedly
      improved compared with pure crystalline CEL; moreover, oral bioavailability of
      CEL loaded into UMCS was also markedly improved compared with that of
      commercially available capsules. UMCS indicates the advantages and potential of
      this method to achieve improved oral absorption by increasing the dissolution
      rate, cellular uptake and permeability of the drug. 

PMID- 24870200
TI  - Influence of glycyrrhizin on permeability and elasticity of cell membrane:
      perspectives for drugs delivery.
AB  - Glycyrrhizin or glycyrrhizic acid (GA) - triterpene glycoside extracted from
      licorice root - has been intensively studied over the past decade and is
      considered to be a potential drug delivery system. Glycyrrhizin was found to
      enhance the therapeutic effect of various drugs; however the detailed mechanism
      of these effects is still unknown and attracts the attention of researchers. In
      this work, we have made an attempt to clarify the mechanism of Glycyrrhizin
      activity on molecular and cellular level. The influence of GA on the functional
      properties of biomembranes was investigated via NMR spectroscopy and atomic force
      microscopy (AFM) using human erythrocytes as a model system. GA was shown to
      increase the permeability (about 60%) and to decrease elasticity modulus of cell
      membranes (by an order of magnitude) even in micromolar concentrations. Changes
      on the erythrocyte surface were also detected by AFM. These results could provide
      a new insight on the mechanism of bioavailability enhancement of some drugs in
      the presence of glycyrrhizin, as well as the mechanism of its own biological
      activity. The role of cholesterol-glycyrrhizin binding in the observed effects is
      also discussed. 

PMID- 24870201
TI  - Antitumor activity of electrospun polylactide nanofibers loaded with 5
      fluorouracil and oxaliplatin against colorectal cancer.
AB  - The purpose of this study was to evaluate both in vitro and in vivo anticancer
      activities against colorectal cancer (CRC) of electrospun polylactide (PLA)
      nanofibers loaded with 5-fluorouracil (5-Flu) and oxaliplatin. For in vitro
      evaluation, human CRC HCT8 cells were directly exposed to the drug-loaded fiber
      mats, followed with MTT and flow cytometry (FCM) assay. For in vivo evaluation,
      the drug-loaded fiber mats were locally implanted into mouse colorectal CT26
      tumor-bearing mice, followed with histological analysis and detection of survival
      rate. The results showed that the drug-loaded fiber mats was similar to that of
      the combination of free 5-Flu and oxaliplatin in vitro cytotoxicity but was much
      superior to intravenous injection of free drug in vivo anticancer activities,
      presenting with suppressed tumor growth rate and prolonged survival time of mice.
      In conclusion, anticancer activities of 5-Flu and oxaliplatin against CRC can be
      significantly improved by using PLA electrospun nanofibers as local drug delivery
      system. 

PMID- 24870202
TI  - A novel electrospun membrane based on moxifloxacin hydrochloride/poly(vinyl
      alcohol)/sodium alginate for antibacterial wound dressings in practical
      application.
AB  - This study reports on the performance of sodium alginate (SA)/poly(vinyl alcohol)
      (PVA)/moxifloxacin hydrochloride (MH) nanofibrous membranes (NFM) capable of
      providing antibacterial agent delivery for wound-dressing applications. The aim
      of this work was to prepare antibacterial NFM with good permeability properties
      by employing PVA and SA as carriers. A group of 12% PVA/2% SA solutions blended
      in various ratios (8:2, 7:3, 6:4, 5:5 and 4:6, v/v) and containing 0.5, 1, 2 or 4
      wt% MH were studied for electrospinning into nanoscale fibermats. The optimum
      ratio found to form smooth fibers with uniform fibrous features was 6:4. The drug
      release behavior of the electrospun, the antibacterial effects on Pseudomonas
      aeruginosa and Staphylococcus aureus and the animal wound dressing capabilities
      were also investigated. As much as 80% of the MH was released from the
      electrospun after 10 h of incubation at 37  degrees C. In addition, the NFM with
      0.5 MH exhibited less activity, whereas those with higher concentrations of MH
      exhibited greater antibacterial effect. Furthermore, the MH-loaded electrospun
      accelerated the rate of wound dressing compared to other groups. The results of
      the in vitro and in vivo experiments suggest that MH/PVA/SA nanofibers might be
      an interesting bioactive wound dressing for clinical applications. 

PMID- 24870203
TI  - Development and characterization of spray-dried porous nanoaggregates for
      pulmonary delivery of anti-tubercular drugs.
AB  - Tuberculosis, MTB or tubercle bacillus (TB) is a lethal, infectious disease
      mainly caused by various strains of mycobacteria, usually Mycobacterium
      tuberculosis. In this study, guar gum-based porous nanoaggregates were formulated
      by precipitation technique with two frontline antitubercular drugs, i.e.
      isoniazid and rifampicin. The formulations were optimized on the basis of various
      evaluation parameters such as morphology, density, entrapment efficiency and in
      vitro drug release. The optimized formulations were administered by inhalable
      route to Wistar rats for the evaluation of drugs in different organs (lungs,
      liver and kidneys). High drug encapsulation efficiency was achieved in guar gum
      porous nanoaggregates, ranging from 50% to 60%. A single pulmonary dose resulted
      in therapeutic drug concentrations of 30%-50% in the lungs and in other organs
      (less than 5%) for 24 h. From this study, we can conclude that delivering drugs
      through pulmonary route is advantageous for local action in lungs. Furthermore,
      the formulation showed sustained drug release pattern, which could be beneficial
      for reducing the drug dose or frequency of dosing, thus helpful in improving
      patient compliance. 

PMID- 24870204
TI  - Preparation and in vitro evaluation of thienorphine-loaded PLGA nanoparticles.
AB  - Poly (d,l-lactic-co-glycolide) nanoparticles (PLGA-NPs) have attracted
      considerable interest as new delivery vehicles for small molecules, with the
      potential to overcome issue such as poor drug solubility and cell permeability.
      However, their negative surface charge decreases bioavailability under oral
      administration. Recently, cationically modified PLGA-NPs has been introduced as
      novel carriers for oral delivery. In this study, our aim was to introduce and
      evaluate the physiochemical characteristics and bioadhesion of positively charged
      chitosan-coated PLGA-NPs (CS-PLGA-NPs), using thienorphine as a model drug. These
      results indicated that both CS-PLGA-NPs and PLGA-NPs had a narrow size
      distribution, averaging less than 130 nm. CS-PLGA-NPs was positively charged
      (+42.1 +/- 0.4 mV), exhibiting the cationic nature of chitosan, whereas PLGA-NPs
      showed a negative surface charge (-2.01 +/- 0.3 mV). CS-PLGA-NPs exhibited
      stronger bioadhesive potency than PLGA-NPs. Furthermore, the transport of
      thienorphine-CS-PLGA-NPs by Caco-2 cells was higher than thienorphine-PLGA-NPs or
      thienorphine solution. CS-PLGA-NPs were also found to significantly enhance
      cellular uptake compared with PLGA-NPs on Caco-2 cells. An evaluation of
      cytotoxicity showed no increase in toxicity in either kind of nanoparticles
      during the formulation process. The study proves that CS-PLGA-NPs can be used as
      a vector in oral drug delivery systems for thienorphine due to its positive
      surface charge and bioadhesive properties. 

PMID- 24870205
TI  - Imaging diagnosis--disseminated peritoneal leiomyomatosis in a dog.
AB  - A 17-month-old male Labrador retriever presented for evaluation of an abdominal
      mass felt during abdominal palpation. Multiple variably sized cystic masses were
      identified on sonographic and radiographic images. Exploratory laparotomy
      revealed multiple peritoneal masses that exhibited atypical contractions and
      lacked an identifiable organ of origin. Histology and immunohistochemistry of
      multiple surgically excised masses was consistent with benign tumors of smooth
      muscle origin (leiomyomas). The presence of multiple peritoneal leiomyomas in
      this dog is consistent with disseminated peritoneal leiomyomatosis. Two years
      after diagnosis and multiple surgical interventions, continual insidious
      enlargement of leiomyomas was identified on ultrasound and CT. 

PMID- 24870206
TI  - Healthy People 2020: a report card on the health of the nation.

PMID- 24870207
TI  - Authors' response: Epithelial-mesenchymal Transition (EMT) is a common molecular
      programme in epithelial cells which can be triggered by injury.

PMID- 24870208
TI  - Innate immunity in paediatric viral wheezers is virus specific and not interferon
      dependent.

PMID- 24870209
TI  - Exploring in-hospital adverse drug events using ICD-10 codes.
AB  - OBJECTIVE: Adverse drug events (ADEs) during hospital admissions are a widespread
      problem associated with adverse patient outcomes. The 'external cause' codes in
      the International Statistical Classification of Diseases and Related Health
      Problems 10th Revision (ICD-10) provide opportunities for identifying the
      incidence of ADEs acquired during hospital stays that may assist in targeting
      interventions to decrease their occurrence. The aim of the present study was to
      use routine administrative data to identify ADEs acquired during hospital
      admissions in a suburban healthcare network in Melbourne, Australia. METHODS:
      Thirty-nine secondary diagnosis fields of hospital discharge data for a 1-year
      period were reviewed for 'diagnoses not present on admission' and assigned to the
      Classification of Hospital Acquired Diagnoses (CHADx) subclasses. Discharges with
      one or more ADE subclass were extracted for retrospective analysis. RESULTS: From
      57205 hospital discharges, 7891 discharges (13.8%) had at least one CHADx, and
      402 discharges (0.7%) had an ADE recorded. The highest proportion of ADEs was due
      to administration of analgesics (27%) and systemic antibiotics (23%). Other major
      contributors were anticoagulation (13%), anaesthesia (9%) and medications with
      cardiovascular side-effects (9%). CONCLUSION: Hospital data coded in ICD-10 can
      be used to identify ADEs that occur during hospital stays and also clinical
      conditions, therapeutic drug classes and treating units where these occur. Using
      the CHADx algorithm on administrative datasets provides a consistent and
      economical method for such ADE monitoring.

PMID- 24870210
TI  - Evidence-based practice competence: a concept analysis.
AB  - PURPOSE: To report an analysis of the concept of evidence-based practice
      competence for nurses using Walker and Avant's (2011) eight-step, iterative
      concept analysis process as a guide. DATA SOURCES: Cumulative Index to Nursing
      and Allied Health Literature, PubMed, OVID, PsycINFO, and Sociological Abstracts
      were searched. DATA SYNTHESIS: References were read and analyzed according to
      associated meanings, usages, attributes, antecedents, consequences, and empirical
      referents. CONCLUSION: An operational definition for the concept was developed.
      IMPLICATIONS FOR NURSING PRACTICE: A clear and operational definition of evidence
      based practice competence will help guide nurses at all levels of experience to
      use the best available evidence for improving the quality of care and maximizing
      patient outcomes.

PMID- 24870211
TI  - Benzo annulated cycloheptatriene PCP pincer iridium complexes.
AB  - The benzo annulated cycloheptatriene PCP pincer ligand was prepared in five
      steps. Treatment of with Ir(CO)3Cl gave the meridional cyclometalated
      chlorohydrido carbonyl iridium complexes which differ in their arrangement of the
      H, Cl, and CO ligands around iridium. Storing in THF led to isomerization
      processes. Hydrogen shifts from the sp(3)-CH carbon bound to iridium into the
      ligand backbone produced the three isomers . Reductive elimination of HCl from
      these complexes resulted in the square planar Ir(i) carbonyl complexes .
      Abstraction of the hydrogen from the sp(3)-CH-Ir fragment could be achieved
      either by treatment of with Ph3CBF4 or by the elimination of H2 which is
      initiated by CF3SO3H. The mass spectrometric characterisation of using fast atom
      bombardment reveals a complex fragmentation pattern. These different "fragment"
      ions were further investigated by electro-spray ionisation (tandem) mass
      spectrometry in high and low resolution. The identified compounds were attributed
      to structures by DFT calculations. 

PMID- 24870212
TI  - Two-chamber hydrogen generation and application: access to pressurized deuterium
      gas.
AB  - Hydrogen and deuterium gas were produced and directly applied in a two-chamber
      system. These gaseous reagents were generated by the simple reaction of metallic
      zinc with HCl in water for H2 and DCl in deuterated water for D2. The setup
      proved efficient in classical Pd-catalyzed reductions of ketones, alkynes,
      alkenes, etc. in near-quantitative yields. The method was extended to the
      synthesis and isotope labeling of quinoline and 1,2,3,4-tetrahydroquinoline
      derivatives. Finally, CX-546 and Olaparib underwent efficient Ir-catalyzed
      hydrogen isotope exchange reactions. 

PMID- 24870213
TI  - Primary repair or fecal diversion for colorectal injuries after blast: a medical
      review.
AB  - Blast injury is a frequent cause of injury during armed conflicts, and the force
      of a blast can cause closed colorectal injury and perforation.1 After
      identification of a blast-related colorectal injury, the surgical options are
      primary repair or fecal diversion with the option for secondary repair. This
      structured review was conducted to determine which patients could be treated with
      primary repair (PR) or with fecal diversion. The review method followed the
      Prisma Statement method for medical systematic review. All data from the relevant
      articles were collected in a single database. Articles took into account wars in
      Bosnia, Iraq and Afghanistan from January 1993 through November 2012. The review
      was limited due to lack of reported data, hence qualitative analysis was the main
      review method. The review showed that for patients who do not have associated
      intra-abdominal injuries (diaphragm, stomach, pancreas, spleen, or kidney) or
      hemodynamic instability, PR did not result in an increase of complications or
      mortality.

PMID- 24870215
TI  - Reply: To PMID 24841141.

PMID- 24870214
TI  - Phthalate exposure and risk assessment in California child care facilities.
AB  - Approximately 13 million U.S. children less than 6 years old spend some time in
      early childhood education (ECE) facilities where they may be exposed to
      potentially harmful chemicals during critical periods of development. We measured
      five phthalate esters in indoor dust (n = 39) and indoor and outdoor air (n = 40
      and 14, respectively) at ECE facilities in Northern California. Dust and airborne
      concentrations were used to perform a probabilistic health risk assessment to
      compare estimated exposures with risk levels established for chemicals causing
      reproductive toxicity and cancer under California's Proposition 65. Di(2
      ethylhexyl) phthalate (DEHP) and butyl benzyl phthalate (BBzP) were the dominant
      phthalates present in floor dust (medians = 172.2 and 46.8 MUg/g, respectively),
      and dibutyl phthalate (DBP), diethyl phthalate (DEP), and diisobutyl phthalate
      (DIBP) were the dominant phthalates in indoor air (medians = 0.52, 0.21, and 0.10
      MUg/m(3), respectively). The risk assessment results indicate that 82-89% of
      children in California ECE had DBP exposure estimates exceeding reproductive
      health benchmarks. Further, 8-11% of children less than 2 years old had DEHP
      exposure estimates exceeding cancer benchmarks. This is the largest study to
      measure phthalate exposure in U.S. ECE facilities and findings indicate wide
      phthalate contamination and potential risk to developing children. 

PMID- 24870216
TI  - All for one and one for all: accommodating an extra electron in C60.
AB  - Much like the neutral C60 fullerene, the C60(-) anion possesses certain unique
      properties which have attracted a great deal of research. One of these special
      properties, only recently fully uncovered, is that the C60(-) anion supports a
      substantial number of electronically stable excited states in contrast to other
      molecular anions with comparable electron affinity. In this work, we clarify how
      the C60(-) anion can support so many stable states by analyzing the radial and
      angular distributions of the excess electron bound to the anion. The analysis is
      based on ab initio calculations which are by far the most accurate on the C60(-)
      anion to date. Surprisingly, the radial distributions are highly similar for
      states of very different binding energies and the analysis stresses the
      importance of angular correlation in binding the excess electron. We further
      analyze the effect of the single excess electron on the electrons of the
      underlying neutral molecule. We demonstrate how this substantially modifies the
      actual distribution of the excess charge by shifting the underlying electron
      density. Implications of these findings are discussed. 

PMID- 24870217
TI  - Photodissociation dynamics of allyl chloride at 200 and 266 nm studied by time
      resolved mass spectrometry and photoelectron imaging.
AB  - The photodissociation dynamics of allyl chloride at 200 and 266 nm has been
      studied by femtosecond time-resolved mass spectrometry coupled with photoelectron
      imaging. The molecule was prepared to different excited states by selectively
      pumping with 400 or 266 nm pulse. The dissociated products were then probed by
      multiphoton ionization with 800 nm pulse. After absorbing two photons at 400 nm,
      several dissociation channels were directly observed from the mass spectrum. The
      two important channels, C-Cl fission and HCl elimination, were found to decay
      with multiexponential functions. For C-Cl fission, two time constants, 48 +/- 1
      fs and 85 +/- 40 ps, were observed. The first one was due to the fast
      predissociation process on the repulsive nsigma*/pisigma* state. The second one
      could be ascribed to dissociation on the vibrationally excited ground state which
      is generated after internal conversion from the initially prepared pipi* state.
      HCl elimination, which is a typical example of a molecular elimination reaction,
      was found to proceed with two time constants, 600 +/- 135 fs and 14 +/- 2 ps. We
      assigned the first one to dissociation on the excited state and the second one to
      the internal conversion from the pipi* state to the ground state and then
      dissociation on the ground state. As we excited the molecule with 266 nm light,
      the transient signals decayed exponentially with a time constant of ~48 fs, which
      is coincident with the time scale of C-halogen direct dissociation. Photoelectron
      images, which provided translational and angular distributions of the generated
      electron, were also recorded. Detailed analysis of the kinetic energy
      distribution strongly suggested that C3H4(+) and C3H5(+) were generated from
      ionization of the neutral radical. The present study reveals the dissociation
      dynamics of allyl chloride in a time-resolved way. 

PMID- 24870221
TI  - Neuroleptic malignant syndrome induced by phenytoin in a patient with drug
      induced Parkinsonism.

PMID- 24870222
TI  - Bilateral ptosis with wall-eyed bilateral internuclear ophthalmoplegia and
      vertical gaze paralysis.

PMID- 24870223
TI  - Guillain-Barre syndrome following measles infection: case report and review of
      the literature.

PMID- 24870220
TI  - Inhibition of GPR137 expression reduces the proliferation and colony formation of
      malignant glioma cells.
AB  - GPR137 are ubiquitously expressed in the central nervous system. However, the
      role o f GPR137 in human malignant glioma is still poorly known. In the present
      study, we firstly detected the expression of GPR137 in 29 human glioma tissue
      specimens by immunohistochemistry and in 5 malignant glioma cell lines by
      quantitative RT-PCR. The expression of GPR137 was much stronger in high-grade
      gliomas than in low-grade gliomas. Lentivirus-mediated small interfering RNAs
      (siRNAs) were employed to knock down GPR137 expression in glioma cells.
      Inhibition of GPR137 expression by RNAi significantly inhibited the proliferation
      and colony-forming capacity of U251, A172 and U373 cells. Moreover, flow
      cytometry analysis showed that knockdown of GPR137 led to the cell-cycle arrest
      at the S phase. Our results indicated that GPR137 is involved in the progression
      of human glioma, suggesting GPR137 as a potential oncogene of glioma cells.

PMID- 24870224
TI  - Identification of major zinc-binding proteins from a marine cyanobacterium:
      insight into metal uptake in oligotrophic environments.
AB  - Marine cyanobacteria make a significant contribution to primary production whilst
      occupying some of the most nutrient poor regions of the world's oceans. The low
      bioavailability of trace metals can limit the growth of phytoplankton in ocean
      waters, but only scarce data are available on the requirements of marine microbes
      for zinc. Recent genome mining studies suggest that marine cyanobacteria have
      both uptake systems for zinc and proteins that utilize zinc as a cofactor. In
      this study, the oligotrophic strain Synechococcus sp. WH8102 was grown at
      different zinc concentrations. Using metalloproteomics approaches, we demonstrate
      that even though this organism's growth was not affected by extremely low zinc
      levels, cells accumulated significant quantities of zinc, which was shown to be
      protein-associated by 2D liquid chromatography and ICP-MS. This indicates that
      the mechanisms for zinc uptake in Synechococcus sp. WH8102 are extremely
      efficient. Significantly, expression of SYNW2224, a putative porin, was up
      regulated during growth in zinc-depleted conditions. Furthermore, along with 30
      other proteins, SYNW2224 was captured by immobilised zinc affinity
      chromatography, indicating the presence of surface-exposed site(s) with metal
      binding capacity. It is proposed that this porin plays a role in high-affinity
      zinc uptake in this and other cyanobacteria. 

PMID- 24870226
TI  - Na+-functionalized carbon quantum dots: a new draw solute in forward osmosis for
      seawater desalination.
AB  - A new type of biocompatible draw solute, Na(+)-functionalized carbon quantum dots
      (Na_CQDs) with ultra-small size and rich ionic species, in forward osmosis (FO)
      is developed for seawater desalination. The aqueous dispersion of Na_CQDs
      demonstrates a high osmotic pressure, which allows high FO water flux and
      negligible reverse solute permeation. 

PMID- 24870227
TI  - Crystalline magnetic carbon nanoparticle assisted photothermal delivery into
      cells using CW near-infrared laser beam.
AB  - Efficient and targeted delivery of impermeable exogenous material such as small
      molecules, proteins, and plasmids into cells in culture as well as in vivo is of
      great importance for drug, vaccine and gene delivery for different therapeutic
      strategies. Though advent of optoporation by ultrafast laser microbeam has
      allowed spatial targeting in cells, the requirement of high peak power to create
      holes on the cell membrane is not practical and also challenging in vivo. Here,
      we report development and use of uniquely non-reactive crystalline magnetic
      carbon nanoparticles (CMCNPs) for photothermal delivery (PTD) of impermeable dyes
      and plasmids encoding light-sensitive proteins into cells using low power
      continuous wave near-infrared (NIR) laser beam. Further, we utilized the magnetic
      nature of these CMCNPs to localize them in desired region by external magnetic
      field, thus minimizing the required number of nanoparticles. We discovered that
      irradiation of the CMCNPs near the desired cell(s) with NIR laser beam leads to
      temperature rise that not only stretch the cell-membrane to ease delivery, it
      also creates fluid flow to allow mobilization of exogenous substances to the
      delivery. Due to significant absorption properties of the CMCNPs in the NIR
      therapeutic window, PTD under in vivo condition is highly possible. 

PMID- 24870228
TI  - Targeted genome editing in human repopulating haematopoietic stem cells.
AB  - Targeted genome editing by artificial nucleases has brought the goal of site
      specific transgene integration and gene correction within the reach of gene
      therapy. However, its application to long-term repopulating haematopoietic stem
      cells (HSCs) has remained elusive. Here we show that poor permissiveness to gene
      transfer and limited proficiency of the homology-directed DNA repair pathway
      constrain gene targeting in human HSCs. By tailoring delivery platforms and
      culture conditions we overcame these barriers and provide stringent evidence of
      targeted integration in human HSCs by long-term multilineage repopulation of
      transplanted mice. We demonstrate the therapeutic potential of our strategy by
      targeting a corrective complementary DNA into the IL2RG gene of HSCs from healthy
      donors and a subject with X-linked severe combined immunodeficiency (SCID-X1).
      Gene-edited HSCs sustained normal haematopoiesis and gave rise to functional
      lymphoid cells that possess a selective growth advantage over those carrying
      disruptive IL2RG mutations. These results open up new avenues for treating SCID
      X1 and other diseases. 

PMID- 24870229
TI  - Receptor binding by H10 influenza viruses.
AB  - H10N8 follows H7N9 and H5N1 as the latest in a line of avian influenza viruses
      that cause serious disease in humans and have become a threat to public health.
      Since December 2013, three human cases of H10N8 infection have been reported, two
      of whom are known to have died. To gather evidence relating to the epidemic
      potential of H10 we have determined the structure of the haemagglutinin of a
      previously isolated avian H10 virus and we present here results relating
      especially to its receptor-binding properties, as these are likely to be major
      determinants of virus transmissibility. Our results show, first, that the H10
      virus possesses high avidity for human receptors and second, from the crystal
      structure of the complex formed by avian H10 haemagglutinin with human receptor,
      it is clear that the conformation of the bound receptor has characteristics of
      both the 1918 H1N1 pandemic virus and the human H7 viruses isolated from patients
      in 2013 (ref. 3). We conclude that avian H10N8 virus has sufficient avidity for
      human receptors to account for its infection of humans but that its preference
      for avian receptors should make avian-receptor-rich human airway mucins an
      effective block to widespread infection. In terms of surveillance, particular
      attention will be paid to the detection of mutations in the receptor-binding site
      of the H10 haemagglutinin that decrease its avidity for avian receptor, and could
      enable it to be more readily transmitted between humans. 

PMID- 24870230
TI  - Analysis of orthologous groups reveals archease and DDX1 as tRNA splicing
      factors.
AB  - RNA ligases have essential roles in many cellular processes in eukaryotes,
      archaea and bacteria, including in RNA repair and stress-induced splicing of
      messenger RNA. In archaea and eukaryotes, RNA ligases also have a role in
      transfer RNA splicing to generate functional tRNAs required for protein
      synthesis. We recently identified the human tRNA splicing ligase, a multimeric
      protein complex with RTCB (also known as HSPC117, C22orf28, FAAP and D10Wsu52e)
      as the essential subunit. The functions of the additional complex components ASW
      (also known as C2orf49), CGI-99 (also known as C14orf166), FAM98B and the DEAD
      box helicase DDX1 in the context of RNA ligation have remained unclear. Taking
      advantage of clusters of eukaryotic orthologous groups, here we find that
      archease (ARCH; also known as ZBTB8OS), a protein of unknown function, is
      required for full activity of the human tRNA ligase complex and, in cooperation
      with DDX1, facilitates the formation of an RTCB-guanylate intermediate central to
      mammalian RNA ligation. Our findings define a role for DDX1 in the context of the
      human tRNA ligase complex and suggest that the widespread co-occurrence of
      archease and RtcB proteins implies evolutionary conservation of their functional
      interplay. 

PMID- 24870231
TI  - Immunology: When lymphocytes run out of steam.

PMID- 24870232
TI  - Millennial-scale variability in Antarctic ice-sheet discharge during the last
      deglaciation.
AB  - Our understanding of the deglacial evolution of the Antarctic Ice Sheet (AIS)
      following the Last Glacial Maximum (26,000-19,000 years ago) is based largely on
      a few well-dated but temporally and geographically restricted terrestrial and
      shallow-marine sequences. This sparseness limits our understanding of the
      dominant feedbacks between the AIS, Southern Hemisphere climate and global sea
      level. Marine records of iceberg-rafted debris (IBRD) provide a nearly continuous
      signal of ice-sheet dynamics and variability. IBRD records from the North
      Atlantic Ocean have been widely used to reconstruct variability in Northern
      Hemisphere ice sheets, but comparable records from the Southern Ocean of the AIS
      are lacking because of the low resolution and large dating uncertainties in
      existing sediment cores. Here we present two well-dated, high-resolution IBRD
      records that capture a spatially integrated signal of AIS variability during the
      last deglaciation. We document eight events of increased iceberg flux from
      various parts of the AIS between 20,000 and 9,000 years ago, in marked contrast
      to previous scenarios which identified the main AIS retreat as occurring after
      meltwater pulse 1A and continuing into the late Holocene epoch. The highest IBRD
      flux occurred 14,600 years ago, providing the first direct evidence for an
      Antarctic contribution to meltwater pulse 1A. Climate model simulations with AIS
      freshwater forcing identify a positive feedback between poleward transport of
      Circumpolar Deep Water, subsurface warming and AIS melt, suggesting that small
      perturbations to the ice sheet can be substantially enhanced, providing a
      possible mechanism for rapid sea-level rise. 

PMID- 24870233
TI  - Climate science: How Antarctic ice retreats.

PMID- 24870234
TI  - mTORC1 controls the adaptive transition of quiescent stem cells from G0 to
      G(Alert).
AB  - A unique property of many adult stem cells is their ability to exist in a non
      cycling, quiescent state. Although quiescence serves an essential role in
      preserving stem cell function until the stem cell is needed in tissue homeostasis
      or repair, defects in quiescence can lead to an impairment in tissue function.
      The extent to which stem cells can regulate quiescence is unknown. Here we show
      that the stem cell quiescent state is composed of two distinct functional phases,
      G0 and an 'alert' phase we term G(Alert). Stem cells actively and reversibly
      transition between these phases in response to injury-induced systemic signals.
      Using genetic mouse models specific to muscle stem cells (or satellite cells), we
      show that mTORC1 activity is necessary and sufficient for the transition of
      satellite cells from G0 into G(Alert) and that signalling through the HGF
      receptor cMet is also necessary. We also identify G0-to-G(Alert) transitions in
      several populations of quiescent stem cells. Quiescent stem cells that transition
      into G(Alert) possess enhanced tissue regenerative function. We propose that the
      transition of quiescent stem cells into G(Alert) functions as an 'alerting'
      mechanism, an adaptive response that positions stem cells to respond rapidly
      under conditions of injury and stress, priming them for cell cycle entry.

PMID- 24870235
TI  - Cntnap4 differentially contributes to GABAergic and   dopaminergic synaptic
      transmission.
AB  - Although considerable evidence suggests that the chemical synapse is a lynchpin
      underlying affective disorders, how molecular insults differentially affect
      specific synaptic connections remains poorly understood. For instance, Neurexin
      1a and 2 (NRXN1 and NRXN2) and CNTNAP2 (also known as CASPR2), all members of the
      neurexin superfamily of transmembrane molecules, have been implicated in
      neuropsychiatric disorders. However, their loss leads to deficits that have been
      best characterized with regard to their effect on excitatory cells. Notably,
      other disease-associated genes such as BDNF and ERBB4 implicate specific
      interneuron synapses in psychiatric disorders. Consistent with this, cortical
      interneuron dysfunction has been linked to epilepsy, schizophrenia and autism.
      Using a microarray screen that focused upon synapse-associated molecules, we
      identified Cntnap4 (contactin associated protein-like 4, also known as Caspr4) as
      highly enriched in developing murine interneurons. In this study we show that
      Cntnap4 is localized presynaptically and its loss leads to a reduction in the
      output of cortical parvalbumin (PV)-positive GABAergic (gamma-aminobutyric acid
      producing) basket cells. Paradoxically, the loss of Cntnap4 augments midbrain
      dopaminergic release in the nucleus accumbens. In Cntnap4 mutant mice, synaptic
      defects in these disease-relevant neuronal populations are mirrored by sensory
      motor gating and grooming endophenotypes; these symptoms could be
      pharmacologically reversed, providing promise for therapeutic intervention in
      psychiatric disorders.

PMID- 24870236
TI  - The sonic hedgehog factor GLI1 imparts drug resistance through inducible
      glucuronidation.
AB  - Drug resistance is a major hurdle in oncology. Responses of acute myeloid
      leukaemia (AML) patients to cytarabine (Ara-C)-based therapies are often short
      lived with a median overall survival of months. Therapies are under development
      to improve outcomes and include targeting the eukaryotic translation initiation
      factor (eIF4E) with its inhibitor ribavirin. In a Phase II clinical trial in poor
      prognosis AML, ribavirin monotherapy yielded promising responses including
      remissions; however, all patients relapsed. Here we identify a novel form of drug
      resistance to ribavirin and Ara-C. We observe that the sonic hedgehog
      transcription factor glioma-associated protein 1 (GLI1) and the UDP
      glucuronosyltransferase (UGT1A) family of enzymes are elevated in resistant
      cells. UGT1As add glucuronic acid to many drugs, modifying their activity in
      diverse tissues. GLI1 alone is sufficient to drive UGT1A-dependent
      glucuronidation of ribavirin and Ara-C, and thus drug resistance. Resistance is
      overcome by genetic or pharmacological inhibition of GLI1, revealing a potential
      strategy to overcome drug resistance in some patients. 

PMID- 24870237
TI  - Accurate design of co-assembling multi-component protein nanomaterials.
AB  - The self-assembly of proteins into highly ordered nanoscale architectures is a
      hallmark of biological systems. The sophisticated functions of these molecular
      machines have inspired the development of methods to engineer self-assembling
      protein nanostructures; however, the design of multi-component protein
      nanomaterials with high accuracy remains an outstanding challenge. Here we report
      a computational method for designing protein nanomaterials in which multiple
      copies of two distinct subunits co-assemble into a specific architecture. We use
      the method to design five 24-subunit cage-like protein nanomaterials in two
      distinct symmetric architectures and experimentally demonstrate that their
      structures are in close agreement with the computational design models. The
      accuracy of the method and the number and variety of two-component materials that
      it makes accessible suggest a route to the construction of functional protein
      nanomaterials tailored to specific applications. 

PMID- 24870238
TI  - RLIM is dispensable for X-chromosome inactivation in the mouse embryonic
      epiblast.
AB  - In female mice, two forms of X-chromosome inactivation (XCI) ensure the selective
      silencing of female sex chromosomes during mouse embryogenesis. Beginning at the
      four-cell stage, imprinted XCI (iXCI) exclusively silences the paternal X
      chromosome. Later, around implantation, epiblast cells of the inner cell mass
      that give rise to the embryo reactivate the paternal X chromosome and undergo a
      random form of XCI (rXCI). Xist, a long non-coding RNA crucial for both forms of
      XCI, is activated by the ubiquitin ligase RLIM (also known as Rnf12). Although
      RLIM is required for triggering iXCI in mice, its importance for rXCI has been
      controversial. Here we show that RLIM levels are downregulated in embryonic cells
      undergoing rXCI. Using mouse genetics we demonstrate that female cells lacking
      RLIM from pre-implantation stages onwards show hallmarks of XCI, including Xist
      clouds and H3K27me3 foci, and have full embryogenic potential. These results
      provide evidence that RLIM is dispensable for rXCI, indicating that in mice an
      RLIM-independent mechanism activates Xist in the embryo proper. 

PMID- 24870239
TI  - Genomic divergence in a ring species complex.
AB  - Ring species provide particularly clear demonstrations of how one species can
      gradually evolve into two, but are rare in nature. In the greenish warbler
      (Phylloscopus trochiloides) species complex, a ring of populations wraps around
      Tibet. Two reproductively isolated forms co-exist in central Siberia, with a
      gradient of genetic and phenotypic characteristics through the southern chain of
      populations connecting them. Previous genetic evidence has proven inconclusive,
      however, regarding whether species divergence took place in the face of
      continuous gene flow and whether hybridization between the terminal forms of the
      ring ever occurred. Here we use genome-wide analyses to show that, although
      spatial patterns of genetic variation are currently mostly as expected of a ring
      species, historical breaks in gene flow have existed at more than one location
      around the ring, and the two Siberian forms have occasionally interbred.
      Substantial periods of geographical isolation occurred not only in the north but
      also in the western Himalayas, where there is now an extensive hybrid zone
      between genetically divergent forms. Limited asymmetric introgression has
      occurred directly between the Siberian forms, although it has not caused a
      blending of those forms, suggesting selection against introgressed genes in the
      novel genetic background. Levels of reproductive isolation and genetic
      introgression are consistent with levels of phenotypic divergence around the
      ring, with phenotypic similarity and extensive interbreeding across the
      southwestern contact zone and strong phenotypic divergence and nearly complete
      reproductive isolation across the northern contact zone. These results cast doubt
      on the hypothesis that the greenish warbler should be viewed as a rare example of
      speciation by distance, but demonstrate that the greenish warbler displays a
      continuum from slightly divergent neighbouring populations to almost fully
      reproductively isolated species. 

PMID- 24870240
TI  - Palladium-catalysed C-H activation of aliphatic amines to give strained nitrogen
      heterocycles.
AB  - The development of new chemical transformations based on catalytic
      functionalization of unactivated C-H bonds has the potential to simplify the
      synthesis of complex molecules dramatically. Transition metal catalysis has
      emerged as a powerful tool with which to convert these unreactive bonds into
      carbon-carbon and carbon-heteroatom bonds, but the selective transformation of
      aliphatic C-H bonds is still a challenge. The most successful approaches involve
      a 'directing group', which positions the metal catalyst near a particular C-H
      bond, so that the C-H functionalization step occurs via cyclometallation. Most
      directed aliphatic C-H activation processes proceed through a five-membered-ring
      cyclometallated intermediate. Considering the number of new reactions that have
      arisen from such intermediates, it seems likely that identification of distinct
      cyclometallation pathways would lead to the development of other useful chemical
      transformations. Here we report a palladium-catalysed C-H bond activation mode
      that proceeds through a four-membered-ring cyclopalladation pathway. The
      chemistry described here leads to the selective transformation of a methyl group
      that is adjacent to an unprotected secondary amine into a synthetically versatile
      nitrogen heterocycle. The scope of this previously unknown bond disconnection is
      highlighted through the development of C-H amination and carbonylation processes,
      leading to the synthesis of aziridines and beta-lactams (respectively), and is
      suggestive of a generic C-H functionalization platform that could simplify the
      synthesis of aliphatic secondary amines, a class of small molecules that are
      particularly important features of many pharmaceutical agents. 

PMID- 24870242
TI  - Seasonal not annual rainfall determines grassland biomass response to carbon
      dioxide.
AB  - The rising atmospheric concentration of carbon dioxide (CO2) should stimulate
      ecosystem productivity, but to what extent is highly uncertain, particularly when
      combined with changing temperature and precipitation. Ecosystem response to CO2
      is complicated by biogeochemical feedbacks but must be understood if carbon
      storage and associated dampening of climate warming are to be predicted.
      Feedbacks through the hydrological cycle are particularly important and the
      physiology is well known; elevated CO2 reduces stomatal conductance and increases
      plant water use efficiency (the amount of water required to produce a unit of
      plant dry matter). The CO2 response should consequently be strongest when water
      is limiting; although this has been shown in some experiments, it is absent from
      many. Here we show that large annual variation in the stimulation of above-ground
      biomass by elevated CO2 in a mixed C3/C4 temperate grassland can be predicted
      accurately using seasonal rainfall totals; summer rainfall had a positive effect
      but autumn and spring rainfall had negative effects on the CO2 response. Thus,
      the elevated CO2 effect mainly depended upon the balance between summer and
      autumn/spring rainfall. This is partly because high rainfall during cool, moist
      seasons leads to nitrogen limitation, reducing or even preventing biomass
      stimulation by elevated CO2. Importantly, the prediction held whether plots were
      warmed by 2  degrees C or left unwarmed, and was similar for C3 plants and total
      biomass, allowing us to make a powerful generalization about ecosystem responses
      to elevated CO2. This new insight is particularly valuable because climate
      projections predict large changes in the timing of rainfall, even where annual
      totals remain static. Our findings will help resolve apparent differences in the
      outcomes of CO2 experiments and improve the formulation and interpretation of
      models that are insensitive to differences in the seasonal effects of rainfall on
      the CO2 response. 

PMID- 24870241
TI  - CTP synthase 1 deficiency in humans reveals its central role in lymphocyte
      proliferation.
AB  - Lymphocyte functions triggered by antigen recognition and co-stimulation signals
      are associated with a rapid and intense cell division, and hence with metabolism
      adaptation. The nucleotide cytidine 5' triphosphate (CTP) is a precursor required
      for the metabolism of DNA, RNA and phospholipids. CTP originates from two
      sources: a salvage pathway and a de novo synthesis pathway that depends on two
      enzymes, the CTP synthases (or synthetases) 1 and 2 (CTPS1 with CTPS2); the
      respective roles of these two enzymes are not known. CTP synthase activity is a
      potentially important step for DNA synthesis in lymphocytes. Here we report the
      identification of a loss-of-function homozygous mutation (rs145092287) in CTPS1
      in humans that causes a novel and life-threatening immunodeficiency,
      characterized by an impaired capacity of activated T and B cells to proliferate
      in response to antigen receptor-mediated activation. In contrast, proximal and
      distal T-cell receptor (TCR) signalling events and responses were only weakly
      affected by the absence of CTPS1. Activated CTPS1-deficient cells had decreased
      levels of CTP. Normal T-cell proliferation was restored in CTPS1-deficient cells
      by expressing wild-type CTPS1 or by addition of exogenous CTP or its nucleoside
      precursor, cytidine. CTPS1 expression was found to be low in resting T cells, but
      rapidly upregulated following TCR activation. These results highlight a key and
      specific role of CTPS1 in the immune system by its capacity to sustain the
      proliferation of activated lymphocytes during the immune response. CTPS1 may
      therefore represent a therapeutic target of immunosuppressive drugs that could
      specifically dampen lymphocyte activation. 

PMID- 24870243
TI  - Gene therapy: Repair and replace.

PMID- 24870245
TI  - Variance-based sensitivity analysis of biological uncertainties in carbon ion
      therapy.
AB  - PURPOSE: Biological models to estimate the relative biological effectiveness
      (RBE) or the equivalent dose in 2 Gy fractions (EQD2) are needed for treatment
      planning and plan evaluation in carbon ion therapy. We present a model
      independent, Monte Carlo based sensitivity analysis (SA) approach to quantify the
      impact of different uncertainties on the biological models. METHODS AND
      MATERIALS: The Monte Carlo based SA is used for the evaluation of variations in
      biological parameters. The key property of this SA is the high number of
      simulation runs, each with randomized input parameters, allowing for a
      statistical variance-based ranking of the input variations. The potential of this
      SA is shown in a simplified one-dimensional treatment plan optimization. Physical
      properties of carbon ion beams (e.g. fragmentation) are simulated using the Monte
      Carlo code FLUKA. To estimate biological effects of ion beams compared to X-rays,
      we use the Local Effect Model (LEM) in the framework of the linear-quadratic (LQ)
      model. Currently, only uncertainties in the output of the biological models are
      taken into account. RESULTS/CONCLUSIONS: The presented SA is suitable for
      evaluation of the impact of variations in biological parameters. Major advantages
      are the possibility to access and display the sensitivity of the evaluated
      quantity on several parameter variations at the same time. Main challenges for
      later use in three-dimensional treatment plan evaluation are computational time
      and memory usage. The presented SA can be performed with any analytical or
      numerical function and hence be applied to any biological model used in carbon
      ion therapy.

PMID- 24870244
TI  - Cyclin D1-Cdk4 controls glucose metabolism independently of cell cycle
      progression.
AB  - Insulin constitutes a principal evolutionarily conserved hormonal axis for
      maintaining glucose homeostasis; dysregulation of this axis causes diabetes. PGC
      1alpha (peroxisome-proliferator-activated receptor-gamma coactivator-1alpha)
      links insulin signalling to the expression of glucose and lipid metabolic genes.
      The histone acetyltransferase GCN5 (general control non-repressed protein 5)
      acetylates PGC-1alpha and suppresses its transcriptional activity, whereas
      sirtuin 1 deacetylates and activates PGC-1alpha. Although insulin is a mitogenic
      signal in proliferative cells, whether components of the cell cycle machinery
      contribute to its metabolic action is poorly understood. Here we report that in
      mice insulin activates cyclin D1-cyclin-dependent kinase 4 (Cdk4), which, in
      turn, increases GCN5 acetyltransferase activity and suppresses hepatic glucose
      production independently of cell cycle progression. Through a cell-based high
      throughput chemical screen, we identify a Cdk4 inhibitor that potently decreases
      PGC-1alpha acetylation. Insulin/GSK-3beta (glycogen synthase kinase 3-beta)
      signalling induces cyclin D1 protein stability by sequestering cyclin D1 in the
      nucleus. In parallel, dietary amino acids increase hepatic cyclin D1 messenger
      RNA transcripts. Activated cyclin D1-Cdk4 kinase phosphorylates and activates
      GCN5, which then acetylates and inhibits PGC-1alpha activity on gluconeogenic
      genes. Loss of hepatic cyclin D1 results in increased gluconeogenesis and
      hyperglycaemia. In diabetic models, cyclin D1-Cdk4 is chronically elevated and
      refractory to fasting/feeding transitions; nevertheless further activation of
      this kinase normalizes glycaemia. Our findings show that insulin uses components
      of the cell cycle machinery in post-mitotic cells to control glucose homeostasis
      independently of cell division. 

PMID- 24870247
TI  - When aryldiazonium salts meet vinyl diazoacetates: a cobalt-catalyzed
      regiospecific synthesis of N-arylpyrazoles.
AB  - A cobalt-catalyzed C-N bond formation between aryl diazonium salts and vinyl
      diazoacetates has been developed under relatively mild conditions. The N
      arylpyrazoles have been prepared in moderate to high yields in a regiospecific
      way. 

PMID- 24870246
TI  - The effectiveness of gadolinium MRI to improve target delineation for
      radiotherapy in hepatocellular carcinoma: a comparative study of rigid image
      registration techniques.
AB  - To achieve consistent target delineation in radiotherapy for hepatocellular
      carcinoma (HCC), image registration between simulation CT and diagnostic MRI was
      explored. Twenty patients with advanced HCC were included. The median interval
      between MRI and CT was 11 days. CT was obtained with shallow free breathing and
      MRI at exhale phase. On each CT and MRI, the liver and the gross target volume
      (GTV) were drawn. A rigid image registration was taken according to point
      information of vascular bifurcation (Method[A]) and pixel information of volume
      of interest only including the periphery of the liver (Method[B]) and manually
      drawn liver (Method[C]). In nine cases with an indefinite GTV on CT, a virtual
      sphere was generated at the epicenter of the GTV. The GTV from CT (VGTV[CT]) and
      MRI (VGTV[MR]) and the expanded GTV from MRI (V+GTV[MR]) considering geometrical
      registration error were defined. The underestimation (uncovered V[CT] by V[MR])
      and the overestimation (excessive V[MR] by V[CT]) were calculated. Through a
      paired T-test, the difference between image registration techniques was analyzed.
      For method[A], the underestimation rates of VGTV[MR] and V+GTV[MR] were 16.4 +/-
      8.9% and 3.2 +/- 3.7%, and the overestimation rates were 16.6 +/- 8.7% and 28.4
      +/- 10.3%, respectively. For VGTV[MR] and V+GTV[MR], the underestimation rates
      and overestimation rates of method[A] were better than method[C]. The
      underestimation rates and overestimation rates of the VGTV[MR] were better in
      method[B] than method[C]. By image registration and additional margin, about 97%
      of HCC could be covered. Method[A] or method[B] could be recommended according to
      physician preference. 

PMID- 24870248
TI  - Dectin-1-CD37 association regulates IL-6 expression during Toxoplasma gondii
      infection.
AB  - Toxoplasma gondii can establish chronic infection and is characterized by the
      formation of tissue cysts in the brain. Although T. gondii can infect any kind of
      nucleated cells, macrophages and related mononuclear phagocytes are its preferred
      targets in vivo. Microglial cells are the resident macrophages in the central
      nervous system. It has been reported that CD37, a tetraspanin molecule, is
      expressed exclusively in the immune system; Dectin-1, an important pattern
      recognition receptor, is expressed on the surface of murine primary microglia.
      The Dectin-1-CD37 association can affect Dectin-1-mediated IL-6 secretion.
      However, there is no report concerning the relationship among the expressions of
      Dectin-1, IL-6, and CD37 during T. gondii infection. In the present study,
      Kunming outbred mice were infected with Prugniaud (Pru), a type II strain of T.
      gondii by oral gavage, and BV-2 murine microglial cells were cocultured with RH
      tachyzoites of T. gondii. By H&E and immunohistochemical staining, the results
      showed that marked inflammation and a significantly increased activation of Iba1
      positive microglial cells were observed in the brain tissues of mice infected
      with T. gondii Pru strain at 5 weeks postinfection (p.i.) in comparison of
      uninfected controls. Using quantitative real-time PCR detection, Dectin-1
      messenger RNA (mRNA) expressions were significantly upregulated in both brains at
      3 (P < 0.01), 5 (P < 0.01), 7 (P < 0.01), and 9 (P < 0.05) weeks p.i. and spleens
      at 3, 5, 7, and 9 weeks p.i. (P < 0.01). IL-6 expressions showed similar dynamic
      tendency as that of Dectin-1 in both the brains and spleens at the same times in
      comparison of uninfected controls; CD37 expressions were significantly increased
      in the brain tissues at all the times (P < 0.01) and no significant differences
      in the spleens at 3 weeks p.i. but significantly downregulated in the spleens at
      5, 7, and 9 weeks p.i. (P < 0.01). In vitro study showed that compared with
      uninfected controls, the mRNA expressions of Dectin-1 at 2, 4, 8, and 10 h (P <
      0.01); IL-6 at 8 and 10 h (P < 0.01); and CD37 at 4 (P < 0.05), 8 (P < 0.01), and
      10 h (P < 0.01) were significantly upregulated in BV-2 murine microglial cells
      stimulated with RH tachyzoites of T. gondii. Our data suggested that the
      expression of Dectin-1 was positively correlated with that of IL-6 in toxoplasmic
      encephalitis (TE) mouse model; Dectin-1 interaction with tetraspanin CD37
      regulated IL-6 expression in both the brain tissues of TE mouse model and in the
      T. gongdii-infected BV-2 murine microglial cells.

PMID- 24870251
TI  - Mitochondria-targeted colorimetric and fluorescent probes for hypochlorite and
      their applications for in vivo imaging.
AB  - Two mitochondria-targeted real-time probes were presented, which could
      selectively respond to hypochlorite over other ROS. Meanwhile, the "off-on"
      probes could be successfully applied in the in vivo imaging of hypochlorite in
      living mice. 

PMID- 24870249
TI  - Biochemical characterization and role of the proteasome in the oxidative stress
      response of adult Schistosoma mansoni worms.
AB  - The trematode Schistosoma mansoni, an important parasite of humans, is the
      principle agent of the disease schistosomiasis. In the human host, one of the
      most important stress factors of this parasite is the oxidative stress generated
      by both the metabolism of the worm and the immune system of the host. The
      proteasomal system is responsible for protein homeostasis during oxidative
      stress. The 26S proteasome is a multicatalytic protease formed by two
      compartments, a 20S core and regulatory particle 19S, and controls the
      degradation of intracellular proteins, hence regulating many cellular processes.
      In the present report, we describe the biochemical characterization and role of
      the 20S proteasome in the response of adult S. mansoni worms exposed to hydrogen
      peroxide. Characterization of the response to the oxidative stress included the
      evaluation of viability, egg production, mortality, tegument integrity, and both
      expression and activity of proteasome. We observed decreases in viability, egg
      production as well as 100% mortality at the higher concentrations of hydrogen
      peroxide tested. The main changes observed in the tegument of adult worms were
      peeling as well as the appearance of bubbles and a decrease of spines on the
      tubercles. Furthermore, there were increases in 26S activity to the same extent
      as 20S proteasome activity, although there was increase of 20S proteasome
      content, suggesting that degradation of protein oxidized in adult worms is due to
      the 20S proteasome. It was demonstrated that adult S. mansoni worms are sensitive
      to oxidative stress, and that a variety of processes in this parasite are altered
      under this condition. The work contributes to a better understanding of the
      mechanisms employed by S. mansoni to survive under oxidative stress.

PMID- 24870250
TI  - Mosquitoes (Diptera: Culicidae) of metropolitan Hamburg, Germany.
AB  - In Europe, mosquito-related public health concerns are growing due to the
      increasing spread of invasive mosquito species and the recent emergence of
      mosquito-borne arboviruses. A vital backbone in the assessment of these issues is
      detailed knowledge of the mosquito fauna, i.e. regional mosquito inventories. It
      was therefore decided to intensify nationwide investigations on the occurrence
      and distribution of mosquitoes in Germany in order to update old records and to
      detect possible faunal changes. This paper is focussing on a densely populated
      metropolitan region, the federal state of Hamburg and its adjacent environs,
      taking two historical baseline inventories into consideration, spanning almost
      100 years of mosquito research in Hamburg. In the period between 2010 and 2014,
      more than 10,000 juvenile, neonate and adult mosquito specimens were sampled and
      trapped at 105 sites in Hamburg and its environs, of which about 60% have been
      identified to species level, resulting in a total of 33 recorded species. Of
      these, Anopheles algeriensis, Culex modestus, Ochlerotatus caspius, Ochlerotatus
      nigrinus and Ochlerotatus sticticus are new to the area. The most common species
      in Hamburg are Culex pipiens/torrentium and Ochlerotatus annulipes/cantans. In
      contrast, two previously common species, Anopheles atroparvus and Ochlerotatus
      excrucians, were not detected. Despite substantial environmental changes due to
      reconstruction, urbanisation and renaturation in the Hamburg metropolitan region
      in recent decades, there has been remarkably little change within the mosquito
      fauna during the last century.

PMID- 24870252
TI  - Delayed isolated port-site metastasis of gallbladder cancer following
      laparoscopic cholecystectomy: report of two cases.

PMID- 24870253
TI  - Electrically tunable plasmonic behavior of nanocube-polymer nanomaterials induced
      by a redox-active electrochromic polymer.
AB  - We present a plasmon-active hybrid nanomaterial design with electrochemical
      tunability of the localized surface plasmon resonances. The plasmonic-active
      nanostructures are composed of silver nanocube aggregates embedded into an
      electrochromic polymer coating on an indium tin oxide electrode with the nanocube
      aggregation controlled by the surface pressure. Such polymer-nanocube hybrid
      nanomaterials demonstrated unique tunable plasmonic behavior under an applied
      electrochemical potential. A significant reversible experimental peak shift of 22
      nm at an electrical potential of 200 mV has been achieved in these measurements.
      Finite-difference time-domain (FDTD) simulations show that, under full oxidation
      potential, a maximal spectral shift of ca. 80 nm can be potentially achieved,
      which corresponds to a high sensitivity of 178 nm per refractive index unit.
      Furthermore, FDTD modeling suggests that the electrochemically controlled
      tunability of plasmonic peaks is caused by reversible changes in the refractive
      index of the electrochromic polymer coating caused by oxidation or reduction
      reactions under external electrical potential. Consequently, we define the
      orthogonal plasmonic resonance shift as a shift that is orthogonal to the redox
      process responsible for the refractive index change. On the basis of these
      results, we suggest that the combination of anisotropic nanostructures and
      electrochromic matrix has the potential to reversibly electrically tune plasmonic
      resonances over the full visible spectrum. 

PMID- 24870260
TI  - Highlights in advanced prostate cancer from the 2014 American Society of Clinical
      Oncology genitourinary cancers symposium: commentary.

PMID- 24870261
TI  - Assessment of goat activin receptor type IIB knockdown by short hairpin RNAs in
      vitro.
AB  - BACKGROUND: Targeted knockdown of ACVR2B, a receptor for TGF beta superfamily,
      has been seen as a potential candidate to enhance the muscle mass through RNAi
      approach. METHODS: We have evaluated the potential short hairpin RNAs targeting
      goat ACVR2B in human HEK293T cells and goat myoblasts cells by transient
      transfection and measured their knockdown efficiency and possible undesired
      interferon response by quantitative real-time PCR. RESULTS: We observed a
      significant silencing (64-81%) of ACVR2B in 293T cells with all seven shRNAs (sh1
      to sh7) constructs and 16-46% silencing with maximum of 46% by sh6 (p = 0.0318)
      against endogenous ACVR2B whereas up to 66% (p = 0.0002) silencing by sh6 against
      exogenously expressed ACVR2B in goat myoblasts cells. Transient knockdown of
      ACVR2B in goat myoblasts cells by shRNAs did not show significant correlation
      with the expression of MyoD (r = 0.547; p = 0.102), myogenin (r = 0.517; p =
      0.126) and Myf5 (r = 0.262; p = 0.465). As reported earlier, transfection of
      plasmid DNA induced potent interferon response in 293T and goat myoblasts cells.
      CONCLUSIONS: The present study demonstrates the targeted knockdown of ACVR2B by
      shRNAs in HEK293T and goat myoblasts cells in vitro. The transient knockdown of
      ACVR2B by shRNAs in goat myoblasts did not alter the myogenic gene expression
      program. However, shRNAs showing significant knockdown efficiency in our study
      may further be tested for long term and stable knockdown to assess their
      potential to use for enhancing muscle mass in vivo. As reported earlier,
      expression of shRNAs through plasmid expression vectors induces potent interferon
      response raising the concern of safety of its application in vivo.

PMID- 24870263
TI  - Does a global budget superimposed on fee-for-service payments mitigate hospitals'
      medical claims in Taiwan?
AB  - Taiwan's global budgeting for hospital health care, in comparison to other
      countries, assigns a regional budget cap for hospitals' medical benefits claimed
      on the basis of fee-for-service (FFS) payments. This study uses a stays-hospitals
      years database comprising acute myocardial infarction inpatients to examine
      whether the reimbursement policy mitigates the medical benefits claimed to a
      third-payer party during 2000-2008. The estimated results of a nested random
      effects model showed that hospitals attempted to increase their medical benefit
      claims under the influence of initial implementation of global budgeting. The
      magnitudes of hospitals' responses to global budgeting were significantly
      attributed to hospital ownership, accreditation status, and market
      competitiveness of a region. The results imply that the regional budget cap
      superimposed on FFS payments provides only blunt incentive to the hospitals to
      cooperate to contain medical resource utilization, unless a monitoring mechanism
      attached with the payment system. 

PMID- 24870262
TI  - Regional biases in mutation screening due to intratumoural heterogeneity of
      prostate cancer.
AB  - Intratumoural heterogeneity (ITH) leads to regional biases of the mutational
      landscape in a single tumour and may influence the single biopsy-based clinical
      diagnosis and treatment decision. To evaluate the extent of ITH in unifocal
      prostate cancers (PCAs), we analysed multiple regional biopsies from three PCAs,
      using whole-exome sequencing, DNA copy number and gene expression profiling
      analyses. A substantial level of ITH was identified, in that 0-61% and 18-71% of
      somatic variants were common or private, respectively, within a given cancer. The
      enhanced mutation detection rate in the combined sequencing dataset across
      intratumoural biopsies was demonstrated with respect to the total number of
      mutations identified in a given tumour. Allele frequencies of the mutations were
      positively correlated with the levels of intratumoural recurrence (private <
      shared < common), but some common mutations showed low allele frequency,
      suggesting that not all were clonally fixed. Regional biases in the presentation
      of a well-known TMPRSS2-ERG fusion was noted in one PCA and the somatic mutation-
      and copy number-based phylogenetic relationships between intratumoural biopsies
      were largely concordant. Genes showing intratumoural expression variability were
      commonly enriched in the molecular function of eicosanoid metabolism and PCA
      relevant clinical markers. Taken together, our analyses identified a substantial
      level of genetic ITH in unifocal PCAs at the mutation, copy number and expression
      levels, which should be taken into account for the identification of biomarkers
      in the clinical setting.

PMID- 24870264
TI  - Military Medicine Publications: What has Happened in the Past Two Decades?
AB  - BACKGROUND: Military medical personnel, like all other physician specialists,
      face the challenge of keeping updated with developments in their field of
      expertise, in view of the great amount of new medical information published in
      the literature. The availability of the Internet has triggered tremendous changes
      in publication characteristics, and in some fields, the number of publications
      has increased substantially. The emergence of electronic open access journals and
      the improvement in Web search engines has triggered a significant change in the
      publication processes and in accessibility of information. OBJECTIVE: The
      objective of this study was to characterize the temporal trends in the number and
      types of publications in military medicine in the medical literature. METHODS: We
      searched all PubMed-registered publications from January 1, 1990 to December 31,
      2010 using the keywords "military" or "army". We used the publication tag in
      PubMed to identify and examine major publication types. The trends were tested
      using the Mann-Kendall test for trend. RESULTS: Our search yielded 44,443
      publications in military medicine during the evaluation period. Overall, the
      number of publications showed two distinct phases over time: (1) a moderate
      increase from 1990 to 2001 with a mean annual increase of 2.78% (r(2)=.79,
      P<.002), and (2) a steeper mean annual increase of 11.20% (r(2)=.96, P<.002) from
      2002 to 2010. Most of the examined publication types showed a similar pattern.
      The proportion of high-quality-of-evidence publication types (randomized
      controlled trials, systematic reviews, and meta-analyses) increased from 2.91% to
      8.43% of the overall military medicine publications with a mean annual
      incremental increase of 14.20%. These publication types demonstrated a similar
      dual phase pattern of increase (10.01%, r(2)=.80, P<.002 for 1990-2001 and
      20.66%, r(2)=.88, P<.002 for 2002-2010). CONCLUSIONS: We conclude that over the
      past twenty years, scholarly work in the field of military medicine has shown a
      significant increase in volume, particularly among high quality publication
      types. However, practice guidelines remain rare, and meta-analyses are still
      limited in number.

PMID- 24870265
TI  - Effect of weak magnetic field on arsenate and arsenite removal from water by
      zerovalent iron: an XAFS investigation.
AB  - In this study, a weak magnetic field (WMF), superimposed with a permanent magnet,
      was utilized to improve ZVI corrosion and thereby enhance As(V)/As(III) removal
      by ZVI at pHini 3.0-9.0. The experiment with real arsenic-bearing groundwater
      revealed that WMF could greatly improve arsenic removal by ZVI even in the
      presence of various cations and anions. The WMF-induced improvement in
      As(V)/As(III) removal by ZVI should be primarily associated with accelerated ZVI
      corrosion, as evidenced by the pH variation, Fe(2+) release, and the formation of
      corrosion products as characterized with X-ray absorption fine structure
      spectroscopy. The arsenic species analysis in solution/solid phases at pHini 3.0
      revealed that As(III) oxidation to As(V) in aqueous phase preceded its subsequent
      sequestration by the newly formed iron (hydr)oxides. However, both As(V)
      adsorption following As(III) oxidation to As(V) in solution and As(III)
      adsorption preceding its conversion to As(V) in solid phase were observed at
      pHini 5.0-9.0. The application of WMF accelerated the transformation of As(III)
      to As(V) in both aqueous and solid phases at pHini 5.0-9.0 and enhanced the
      oxidation of As(III) to As(V) in solution at pHini 3.0. 

PMID- 24870266
TI  - Energy metabolism and methane production in llamas, sheep and goats fed high- and
      low-quality grass-based diets.
AB  - This study aimed to test whether the digestive and metabolic characteristics of
      pseudo ruminants provide superior ability to utilise low-quality diets compared
      to true ruminants. A total of 18 mature, non-pregnant, non-lactating female
      animals, including six llamas (Lama glama), six Danish Landrace goats and six
      Shropshire sheep, were used in a crossover design study. The experiment lasted
      for two periods of three weeks. Half of the animals were fed either high-quality
      grass hay (HP) or low-quality grass seed straw (LP) during each period. Animals
      were placed in metabolic cages during the last 5 d, and gaseous exchange was
      measured by open-circuit indirect calorimetry for 22 h. Metabolisable energy for
      maintenance (MEm) and fasting energy expenditure (FEExp) were estimated by
      regression approach. Dry matter (DM) intake per kg(0.75) was substantially
      reduced in llamas and sheep, but not in goats, on the LP compared to HP diet.
      Llamas had lower daily energy expenditure (324 kJ . kg(-0.75)) than sheep (416 kJ
      . kg(-0.75)) and goats (404 kJ . kg(-0.75)) on the LP diet. Llamas in comparison
      with sheep and goats had lower methane emission (0.83 vs 1.34 and 1.24 l . d(-1)
      . kg(-0.75), p < 0.05), lower MEm (328 vs 438 and 394 kJ . d(-1) . kg(-0.75), p <
      0.05) and lower FEExp (246 vs 333 and 414 kJ . d(-1) . kg(-0.75), p < 0.05),
      respectively. In conclusion, llamas had lower basal metabolic rate and hence
      maintenance requirements for energy.

PMID- 24870267
TI  - Effects of beta-conglycinin on growth performance, immunoglobulins and intestinal
      mucosal morphology in piglets.
AB  - One of the main causes of allergic reactions in young animals is beta
      conglycinin, an antigenic glycoprotein found in soya beans. Therefore, the
      objective of the study was to investigate the effects of a prior immunisation
      with beta-conglycinin on growth performance, serum immunoglobulin levels and
      intestinal histology in piglets. Forty piglets (7 d of age) were randomly divided
      into four groups of ten piglets each. Piglets of Groups Im and Im+S were
      immunised twice by hypodermic injection with beta-conglycinin at 500 MUg/kg body
      weight (BW) at day 7 and 21 of age. At day 23, Groups Im+S and S were
      intramuscularly injected with 5000 MUg beta-conglycinin per kg BW. The piglets of
      Group C received a physiological saline solution by hypodermic injection. All
      piglets were weaned at the age of 23 d and blood samples were taken on days 7, 21
      and 35. At the end of the trial, five piglets per group were slaughtered and the
      intestine was collected for evaluating mucosal histology. Compared to Group C, in
      Group S the average daily gain (ADG), feed intake and gain:feed ratio were
      decreased (p < 0.01), and serum levels of IgG and IgE were increased (p < 0.01).
      Furthermore, in this group the structure of duodenal and jejunal mucosa was
      severely damaged. But in Groups Im and Im+S the ADG was increased (p < 0.05),
      serum IgE levels were decreased (p < 0.01) and the intestinal mucosa was not
      damaged. The results suggest that prior immunisation with beta-conglycinin can
      increase ADG and serum IgG levels and decrease serum IgE levels. Therefore, this
      method is also potentially able to protect the structural integrity of the
      intestinal mucosal epithelia and alleviate allergic reactions in piglets.

PMID- 24870268
TI  - Determination and prediction of the energy content and amino acid digestibility
      of peanut meals fed to growing pigs.
AB  - Two experiments were conducted to determine the content of digestible energy (DE)
      and metabolisable energy (ME) as well as the apparent ileal digestibility (AID)
      and standardised ileal digestibility (SID) of amino acids in peanut meal (PNM)
      for growing pigs. In Experiment 1, 78 growing pigs (46.8 +/- 2.6 kg) were
      randomly allotted to 1 of 13 diets, including a corn-soya bean meal basal diet
      and 12 PNM test diets. In Experiment 2, 12 growing barrows (48.7 +/- 2.8 kg) were
      allotted to one of two 6 * 6 Latin squares. The treatments include a N-free diet
      and 10 PNM test diets. The results of Experiment 1 showed that the DE and ME
      differed (p < 0.05) among the 12 PNM samples. On a dry matter basis, the DE and
      ME content ranged from 14.5 to 16.4 MJ/kg (mean 15.6 MJ/kg) and from 12.7 to 15.5
      MJ/kg (mean 13.9 MJ/kg), respectively. The apparent total tract digestibility
      (ATTD) of gross energy (GE) was 82.2%. The DE of PNM could be precisely predicted
      by equations including NDF combined with GE or crude protein (CP) with an R(2)
      value of 0.91 and 0.92, respectively. For the AID and SID for lysine, the results
      of Experiment 2 indicated variations among PNM sources ranging from 59.6% to
      76.7% and 64.8% to 80.9%, respectively. However, for CP, variations for AID and
      SID were lower and ranged from 70.2% to 81.9% and 75.7% to 85.6%, respectively.
      The results indicate that the concentration of lysine was the best single
      predictor to estimate the digestibility of amino acids. However, further work is
      needed to investigate the reason for the variation in the digestibility of lysine
      and avoid processing procedures that are detrimental to lysine digestibility.

PMID- 24870269
TI  - Growth performance, gastrointestinal function and meat quality in growing
      finishing turkeys fed diets with different levels of yellow lupine (L. luteus)
      seeds.
AB  - The aim of this study was to evaluate the effects of a different dietary content
      of sweet yellow lupine seed meal (YLM) on gastrointestinal tract development and
      function, the growth performance (13-18 weeks of age) and meat quality of growing
      finishing turkeys. Control grower and finisher diets contained soybean meal
      (SBM), and in experimental diets, SBM was replaced with YLM at 6%, 12% and 18%
      (Groups L6, L12 and L18, respectively). The diets were formulated to be iso
      nitrogenous and iso-energetic. In the first phase of feeding, YLM tended to
      decrease feed intake (p = 0.087) and body weight gain (BWG, p = 0.078) linearly
      due to significant deterioration in feed conversion ratio (FCR, p = 0.030). An
      opposite trend was noted in the second phase of feeding: BWG increased (p =
      0.069) and FCR improved significantly (p = 0.004). Over the entire experiment,
      inclusion of YLM did not affect feed intake, BWG, FCR or excreta dry matter (DM)
      content. The highest YLM dietary level had no adverse effects on fermentation
      processes in the caeca. Positive changes, which were observed in turkeys fed YLM
      supplemented diets, included an increased gizzard weight, a decreased pH of
      gizzard contents and a decreased viscosity of small intestinal digesta. The
      inclusion of YLM at 18% had no effect on carcass quality, the pH and colour
      intensity of breast meat. The highest inclusion rate of YLM (18%) in turkey diets
      significantly (p < 0.05) intensified the fatty flavour of meat and increased its
      hardness, springiness and chewiness, whereas it had no effect on the appearance,
      aroma and overall acceptability of breast meat. It can be concluded that YLM at
      the highest dietary rate used in the present experiment (18% of the diet) had no
      adverse effects on the growth performance or the analysed physiological
      parameters of turkeys.

PMID- 24870270
TI  - Usability of rapeseed cake and wheat-dried distillers' grains with solubles in
      the feeding of growing Californian rabbits.
AB  - By-products of biofuels production such as rapeseed cake and dried distillers'
      grains with solubles (DDGS) may constitute valuable feedstuffs for livestock. The
      objectives of the study were to determine the usability of these components in
      the feeding of growing rabbits and to assess their impact on physiological
      changes in the gastrointestinal tract of the animals. Sixty-four rabbits were
      divided into four feeding groups: Control (5% soyabean meal [SBM] in the diet), R
      (5% rapeseed cake [RSC]), DDGS (5% wheat DDGS), and R/DDGS (2.5% RSC and 2.5%
      wheat DDGS). The study included a production experiment, a digestibility-balance
      experiment and physiological assessment of the functioning of animals'
      gastrointestinal tract (small intestine, caecum and colon). No statistically
      significant differences were determined in production results of the rabbits.
      Digestibility of nutrients and energy and nitrogen retention were the highest in
      the Control and the lowest in Group DDGS. Group DDGS was characterised by the
      highest relative weight of small intestine and digesta. In turn, Group R was
      characterised by the highest degree of caecal digesta hydration and bulking and
      by the highest pH value and the lowest concentration of VFA in caecum. The
      activity of selected bacterial enzymes released to the caecal environment was
      similar in all groups; however, the activity of alpha-arabinopyranosidase was
      significantly increased in Groups R and DDGS. Worthy of notice is the enhanced
      enzymatic activity of colonic microbiota in the R/DDGS group which has a positive
      effect upon increased utilisation of dietary nutrients compared to the DDGS
      group. The obtained results indicate that SBM from rabbit diets may be
      successfully replaced by 5% RSC as well as by 2.5% RSC + 2.5% wheat DDGS.

PMID- 24870271
TI  - Ileal, colonic and total tract nutrient digestibility in dogs (Canis familiaris)
      compared with total tract digestibility in mink (Neovison vison).
AB  - Mink (Neovison vison) was studied as a model for the determination of ileal crude
      protein (CP) and amino acid (AA) digestibility in dogs (Canis familiaris).
      Apparent ileal digestibility (AID) and apparent colonic digestibility (ACD) in
      dogs and apparent total tract digestibility (ATTD) in dogs and mink were measured
      for dry matter (DM), main nutrients and AA. Standardised ileal digestibility
      (SID) of CP and AA in dogs was calculated. Twelve dogs and 12 mink divided into
      three groups were fed one out of three diets differing in CP digestibility. In
      dogs, AID of CP was lower (74.4%) than ATTD (83.5%) (p < 0.001). The ATTD of CP
      in mink (77.8%) did not differ from AID, ACD (78.5%) and SID (79.6%) in dogs.
      Digestibility of AA followed the same pattern, and, except for Thr and Ser, ATTD
      in mink was very close to SID in dogs. Also, AID was close to ATTD in mink for
      several AA. High correlations were found between methods for digestibility of CP
      and most AA (p < 0.01) and for AA ranking with respect to digestibility level (p
      < 0.001). In dogs, ether extract digestibility was approximately 96% at all
      sites, while DM, starch and total carbohydrate digestibility increased from ileal
      to faecal level (p < 0.01). Mink ATTD of DM and main nutrients was closest to ACD
      in dogs. It was concluded that mink is a suitable model for the determination of
      AID and SID of CP and AA in dogs.

PMID- 24870272
TI  - Vesalius on the anatomy and function of the recurrent laryngeal nerves: medical
      illustration and reintroduction of a physiological demonstration from Galen.
AB  - The purpose of this article is to review the anatomical illustrations and
      physiological demonstrations of sixteenth-century Flemish-born anatomist and
      physician Andreas Vesalius concerning the recurrent laryngeal nerves. Although
      Vesalius was primarily an anatomist, he also used vivisection as a pedagogical
      device to help his students understand the function of structures within the
      fabric of the body that they had previously studied in anatomical detail.
      Vesalius's masterwork, De humani corporis fabrica or simply the Fabrica (1543,
      1555), was ostensibly an anatomy text, but Vesalius included textual and figural
      references to his use of vivisection to explicate the function of specific
      structures. Even as he began to criticize the errors in Galen's anatomical works,
      Vesalius nevertheless adopted some of Galen's classic physiological
      demonstrations, in particular the ligation (and subsequent release) of the
      recurrent laryngeal nerves of a pig to demonstrate their role in generating the
      pig's squeal. Vesalius's illustrations concerning the recurrent laryngeal nerve
      in the Fabrica were of two types: elegant anatomical woodcut plates-unsurpassed
      for their clarity, accuracy, and detail - and the distinctly inelegant
      historiated initial Q, depicting a throng of putti busily engaged in vivisecting
      a pig. Vesalius' anatomical plates were heavily plagiarized while the historiated
      initials, showing the rough work of an anatomist or surgeon, were largely ignored
      and remain little recognized today. While Vesalius' anatomical illustrations of
      the recurrent laryngeal nerves contained some errors, they were a dramatic
      departure from prior meager efforts at medical illustration and indeed far
      surpassed all contemporary published illustrations by others. Vesalius was also
      influential in reviving Galen's approach to vivisection, at least for pedagogical
      purposes, if not really then yet as a full-fledged investigative technique. 

PMID- 24870273
TI  - Noninvasive assessment of the risk of tobacco abuse in oral mucosa using
      fluorescence spectroscopy: a clinical approach.
AB  - Tobacco abuse and alcoholism cause cancer, emphysema, and heart disease, which
      contribute to high death rates, globally. Society pays a significant cost for
      these habits whose first demonstration in many cases is in the oral cavity. Oral
      cavity disorders are highly curable if a screening procedure is available to
      diagnose them in the earliest stages. The aim of the study is to identify the
      severity of tobacco abuse, in oral cavity, as reflected by the emission from
      endogenous fluorophores and the chromophore hemoglobin. A group who had no
      tobacco habits and another with a history of tobacco abuse were included in this
      study. To compare the results with a pathological condition, a group of
      leukoplakia patients were also included. Emission from porphyrin and the spectral
      filtering modulation effect of hemoglobin were collected from different sites.
      Multivariate analysis strengthened the spectral features with a sensitivity of
      60% to 100% and a specificity of 76% to 100% for the discrimination. Total
      hemoglobin and porphyrin levels of habitues and leukoplakia groups were
      comparable, indicating the alarming situation about the risk of tobacco abuse.
      Results prove that fluorescence spectroscopy along with multivariate analysis is
      an effective noninvasive tool for the early diagnosis of pathological changes due
      to tobacco abuse.

PMID- 24870274
TI  - A revision of the New World genus Aptilotella Duda (Sphaeroceridae: Limosininae).
AB  - The genus Aptilotella Duda (Diptera: Sphaeroceridae: Limosininae) is redefined
      and revised. The type species, Aptilotella borgmeieri Duda is redescribed, and
      twenty-seven species are described as new: Aptilotella andersoni sp. n., A.
      angela sp. n., A. caerulea sp. n., A. corona sp. n., A. diffisa sp. n., A. ebenea
      sp. n., A. erinacea sp. n., A. gemmula sp. n., A. germana sp. n., A. gladia sp.
      n., A. gloriosa sp. n., A. gracilis sp. n., A. hamata sp. n., A. involucris sp.
      n., A. macta sp. n., A. macula sp. n., A. pennifera sp. n., A. pichin chensis sp.
      n., A. pyropanda sp. n., A. quadrata sp. n., A. quatuorchela sp. n., A. radians
      sp. n., A. simplex sp. n., A. solaria sp. n., A. sphyra sp. n., A. umbracatus sp.
      n., and A. viva sp. n. A phylogenetic analysis and key to species are presented,
      with illustrations and distributional notes.

PMID- 24870275
TI  - The larvae of European Myrmeleontidae (Neuroptera).
AB  - The larvae of the European Myrmeleontidae are reviewed with the aim to ease their
      identification, covering 15 genera and 28 species. Diagnostic characters and
      illustrations are given for each taxon. Larvae of the genera Nemoleon and
      Macronemurus are described for the first time while Megistopus, Neuroleon and
      Myrmeleon are revised. The larvae of Dendroleon pantherinus (Fabricius),
      Macronemurus appendiculatus (Latreille), Megistopus lucasi (Navas), Nemoleon
      notatus (Rambur), Neuroleon arenarius (Navas), Neuroleon assimilis (Navas),
      Neuroleon nemausiensis (Borkhausen), Cueta lineosa (Rambur) and Myrmeleon
      gerlindae (Holzel) are described or accurately depicted for the first time.

PMID- 24870276
TI  - Annotated zoogeography of non-marine Tardigrada. Part I: Central America.
AB  - Dividing the world into nine regions, this first paper describes literature
      records of the limno-terrestrial tardigrades (Tardigrada) reported from Central
      America. Updating previously published species lists we have revised the taxonomy
      and provided additional habitat, geographic co-ordinates, and biogeographic
      comments. It is hoped this work will serve as a reference point and background
      for further zoogeographic studies. 

PMID- 24870277
TI  - Four new species of Rasbora of the Sumatrana group (Teleostei: Cyprinidae) from
      northern Sumatra, Indonesia.
AB  - Four new species of the minnow genus Rasbora of the Sumatrana group, R.
      arundinata, R. haru, R. maninjau, and R. bindumatoga, are described from northern
      Sumatra. Rasbora arundinata is distinguished from all congeners in the Sumatrana
      group by the black midlateral stripe overall forming a reed-leaf-like profile.
      Rasbora haru differs from its congeners in the Sumatrana group in having the
      black midlateral stripe overall forming a stamen-like profile. The new species
      endemic to Lake Maninjau in central west Sumatra, Rasbora maninjau, is unique
      among all the congeners in the Sumatrana group in having a combination of the
      black midlateral stripe extending from the midhumeral region of uniform width,
      the prominent acutely triangular basicaudal blotch, and the oval supra-anal
      pigmentation. Rasbora bindumatoga is distinguished from all congeners in the
      Sumatrana group by a combination of the black rectangular subdorsal blotch, the
      absence of supra-anal pigmentation, and the somewhat oval basicaudal blotch.
      Rasbora arundinata, R. maninjau, and R. bindumatoga occur allopatrically in the
      northwestern coastal region of Sumatra, while R. haru is known from northeastern
      coastal area of Sumatra. A new diagnostic character for the Sumatrana group is
      described: partial exposure of the upper lip due to a submedial contact between
      the maxilla and the lower lip, which is marked posteriorly by a lachrymal groove.

PMID- 24870278
TI  - A new species of Tiwaripotamon Bott, 1970, from northern Vietnam, with notes on
      T. vietnamicum (Dang & Ho, 2002) and T. edostilus Ng & Yeo, 2001 (Crustacea,
      Brachyura, Potamidae).
AB  - A new species of potamid freshwater crab, Tiwaripotamon vixuyenense sp. nov., is
      described from caves in Ha Giang, northern Vietnam. The new species can be
      distinguished from congeners by a suite of characters, including the relatively
      small epibranchial tooth, more slender ambulatory legs and a proportionately
      stout male first gonopod. Molecular data using the mitochondrial cytochrome
      oxidase subunit I (COI) supports its placement as a new species. The molecular
      data also supports the inclusion of another species, Geothelphusa vietnamica Dang
      & Ho, 2002, from Ninh Binh, south of Hanoi, Vietnam in Tiwaripotamon Bott, 1970.
      The live coloration of T. vietnamicum and T. edostilus Ng & Yeo, 2001 is provided
      to help field identification. 

PMID- 24870279
TI  - Seven new Spanish species of the genus Synaldis (Hymenoptera, Braconidae,
      Alysiinae) with mesoscutal pit.
AB  - Descriptions of seven new species of the alysiine genus Synaldis having
      mesoscutal pit from Spain are given: Synaldis berbegalae sp. nov., S. falcoi sp.
      nov., S. gilaberti sp. nov., S. jujisae sp. nov., S. lozanoae sp. nov., S.
      martinezae sp. nov., and S. navarroae sp. nov. 

PMID- 24870280
TI  - Redescription of Limnosida frontosa Sars, 1862 (Crustacea: Cladocera: Sididae),
      with evidence of possible incipient species differentiation.
AB  - Limnosida frontosa Sars, 1862 is redescribed based on the material from over its
      entire range, from Norway and Finland in the west to Yakutia in eastern Siberia
      and the Lower Amur River basin (Far East of Russia) in the east. Morphological
      analysis of the species has revealed a combination of advanced and evolutionary
      primitive features, latter characterizing Limnosida as the most primitive member
      of the order Ctenopoda. Investigation of intra- and interpopulational
      morphological variability, in particular of the post abdominal claws, led to a
      tentative separation of the species into two main forms, occurring regionally in
      the north-west and east of Northern Eurasia. Their taxonomic status as yet
      remains unclear. Some overlap in geographical distribution of these forms and the
      presence of populations with intermediate morphological features probably
      reflects irregularity of the diversification process in L. frontosa s.l. within
      its range. This diversification may be the result of both geographic disjunction
      and adaptation to waters of different trophic status. The low level of
      intraspecies differentiation and comparatively limited geographic distribution of
      this species imply its young age while the genus Limnosida itself is presumed
      ancient. 

PMID- 24870281
TI  - Four new species of Pauropoda (Brachypauropodidae, Eurypauropodidae,
      Pauropodidae) from the Sanqingshan Mountains, Jiangxi Province, China.
AB  - Among 46 pauropods collected from the Sanqingshan Mountains in southeastern
      China, four new species were identified: Borneopauropus acutifolius sp. n. in
      Brachypauropodidae, Samarangopus dilatare sp. n. in Eurypauropodidae, both
      families new to China, and two species in Pauropodidae, Decapauropus cutellatus
      sp. n. and D. biaristatus sp. n. 

PMID- 24870282
TI  - Description of a new species of the genus Sarasaeschna Karube & Yeh, with a key
      to the species of Taiwan (Odonata: Anisoptera: Aeshnidae).
AB  - Sarasaeschna chiangchinlii sp. nov. collected from Daxi, Taoyuan County in
      northern Taiwan is described and diagnosed. Judging from male penile structure,
      this species is considered to belong to the pryeri-group of its genus. It is
      easily distinguished from all known congeners in having peculiar sickle-shaped
      cerci in male. The habitats of S. chiangchinlii are mainly shaded brooks in
      lowland areas, which are exceptional for its Taiwanese relatives. Distributional
      maps and a key are also provided for the four species of Taiwanese Sarasaeschna. 

PMID- 24870283
TI  - Agro-industrial wastes as effective amendments for ecotoxicity reduction and soil
      health improvement in aided phytostabilization.
AB  - Aided phytostabilization is a technology that uses metal tolerant plants and
      organic and/or inorganic amendments to reduce soil metal bioavailability, while
      improving soil health. Our objective was to determine the effects of the
      application of amendments [sheep manure (SHEEP), poultry litter (POULTRY), cow
      slurry (COW), and paper mill sludge mixed with poultry litter (PAPER)], together
      with the growth of a metallicolous Festuca rubra L. population, on (i) chemical
      and microbial indicators of soil health and (ii) soil ecotoxicity, during the
      aided phytostabilization of a Zn/Pb contaminated mine soil. Amendment application
      led to an increase in soil pH, organic matter content, and inorganic salts,
      resulting in a decrease in Pb and Zn CaCl2-extractable concentrations in soil,
      which, in turn, contributed to lower ecotoxicity and a stimulation of plant
      growth and soil microbial communities. The factor most affecting the metal
      extractability was probably soil pH. POULTRY was the best amendment in terms of
      increasing plant growth, chlorophylls content, and soil microbial biomass and
      activity, but resulted in higher levels of phytoavailable Pb and Zn. SHEEP and
      PAPER were more effective at reducing metal CaCl2-extractability and,
      consequently, led to lower values of metal accumulation in plant tissues, thereby
      reducing the risk of metals entering into the food chain. When combined with the
      application of organic amendments, the metallicolous F. rubra population studied
      here appears an excellent candidate for aided phytostabilization. Our results
      indicate that the application of organic amendments is essential for the short
      term recovery of highly contaminated metalliferous soils during aided
      phytostabilization. 

PMID- 24870284
TI  - Accumulation and fraction distribution of Ni(II) in activated sludge treating Ni
      laden wastewater.
AB  - The accumulation and fraction distribution of Ni(II) in sludge was determined,
      and their effect on the performance of sequencing batch reactor (SBR) systems was
      evaluated at laboratory scale. The results showed that the removal efficiencies
      of substrates decreased significantly with increasing feeding concentration of
      Ni(II) into SBRs. The concentration of Ni(II) fed into the SBRs was significantly
      positively correlated with the Ni(II) contents accumulated in the sludge, while
      it was negatively correlated with the biomass in the SBRs. The accumulated Ni(II)
      in the sludge was distributed mainly in the available fraction, accounting for
      75.8-90.0 % of the total Ni(II) content. The accumulated content of Ni(II) in
      each sludge fraction could be predicted satisfactorily by the feeding Ni(II)
      concentrations in the solutions. As compared with the total contents and other
      chemical fractions, Ni(II) in the oxidizable fraction in sludge exhibited more
      important inhibition effects on sludge microorganisms in the SBRs.

PMID- 24870285
TI  - Europe-wide survey of estrogenicity in wastewater treatment plant effluents: the
      need for the effect-based monitoring.
AB  - A pan-European monitoring campaign of the wastewater treatment plant (WWTP)
      effluents was conducted to obtain a concise picture on a broad range of
      pollutants including estrogenic compounds. Snapshot samples from 75 WWTP
      effluents were collected and analysed for concentrations of 150 polar organic and
      20 inorganic compounds as well as estrogenicity using the MVLN reporter gene
      assay. The effect-based assessment determined estrogenicity in 27 of 75 samples
      tested with the concentrations ranging from 0.53 to 17.9 ng/L of 17-beta
      estradiol equivalents (EEQ). Approximately one third of municipal WWTP effluents
      contained EEQ greater than 0.5 ng/L EEQ, which confirmed the importance of cities
      as the major contamination source. Beside municipal WWTPs, some treated
      industrial wastewaters also exhibited detectable EEQ, indicating the importance
      to investigate phytoestrogens released from plant processing factories. No
      steroid estrogens were detected in any of the samples by instrumental methods
      above their limits of quantification of 10 ng/L, and none of the other analysed
      classes of chemicals showed correlation with detected EEQs. The study
      demonstrates the need of effect-based monitoring to assess certain classes of
      contaminants such as estrogens, which are known to occur at low concentrations
      being of serious toxicological concern for aquatic biota.

PMID- 24870286
TI  - Three major nucleolar proteins migrate from nucleolus to nucleoplasm and
      cytoplasm in root tip cells of Vicia faba L. exposed to aluminum.
AB  - Results from our previous investigation indicated that Al could affect the
      nucleolus and induce extrusion of silver-staining nucleolar particles containing
      argyrophilic proteins from the nucleolus into the cytoplasm in root tip cells of
      Vicia faba L. So far, the nucleolar proteins involved have not been identified.
      It is well known that nucleophosmin (B23), nucleolin (C23), and fibrillarin are
      three major and multifunctional nucleolar proteins. Therefore, effects of Al on
      B23, C23, and fibrillarin in root tip cells of V. faba exposed to 100 MUM Al for
      48 h were observed and analyzed using indirect immunofluorescence microscopy and
      Western blotting. The results from this work demonstrated that after 100 MUM of
      Al treatment for 48 h, B23 and C23 migrated from the nucleolus to the cytoplasm
      and fibrillarin from the nucleolus to the nucleoplasm. In some cells, fibrillarin
      was present only in the cytoplasm. Western blotting data revealed higher
      expression of the three major nucleolar proteins in Al-treated roots compared
      with the control and that the B23 content increased markedly. These findings
      confirmed our previous observations.

PMID- 24870287
TI  - Inhibition equivalency factors for microcystin variants in recombinant and wild
      type protein phosphatase 1 and 2A assays.
AB  - In this work, protein phosphatase inhibition assays (PPIAs) have been used to
      evaluate the performance of recombinant PP1 and recombinant and wild-type PP2As.
      The enzymes have been compared using microcystins-LR (MC-LR) as a model
      cyanotoxin. Whereas PP2ARec provides a limit of detection (LOD) of 3.1 MUg/L,
      PP1Rec and PP2AWild provide LODs of 0.6 and 0.5 MUg/L, respectively, lower than
      the guideline value proposed by the World Health Organization (1 MUg/L). The
      inhibitory potencies of seven MC variants (-LR, -RR, -dmLR, -YR, -LY, -LW and 
      LF) have been evaluated, resulting on 50 % inhibition coefficient (IC50) values
      ranging from 1.4 to 359.3 MUg/L depending on the MC variant and the PP. The PPIAs
      have been applied to the determination of MC equivalent contents in a natural
      cyanobacterial bloom and an artificially contaminated sample, with multi-MC
      profiles. The inhibition equivalency factors (IEFs) have been applied to the
      individual MC quantifications determined by liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) analysis, and the estimated MC-LR equivalent content has
      been compared to PPIA results. PPIAs have demonstrated to be applicable as MC
      screening tools for environmental applications and to protect human and animal
      health.

PMID- 24870288
TI  - Application of Fenton's reagent combined with sawdust on the dewaterability of
      oily sludge.
AB  - Fenton's reagent and sawdust were used on the dewaterability of the raw oily
      sludge in this study. The result shows that the combination of the two treatment
      processes is favorable, although the application of Fenton's reagent only is not
      so good. The capillary suction time (CST) and specific resistance to filtration
      (SRF) were used to evaluate the effect of dewaterability of the raw oily sludge,
      and the CST and SRF values are reduced from 1,760 s and 13.8 * 10(12) m/kg to 185
      s and 1.5 * 10(12) m/kg, respectively. The dry matter contents of sludge cakes
      and properties of the supernatant all gained when using only the Fenton's reagent
      and when using the combined treatment with Fenton's reagent and sawdust
      respectively were investigated. The results indicate that the oily sludge is more
      suitable for further treatment after combined process with Fenton's reagent and
      sawdust.

PMID- 24870289
TI  - Prevalence of liver diseases as referred by people living in the Santos and Sao
      Vicente Estuary.
AB  - The Santos and Sao Vicente Estuary has suffered extensively over the years from
      irregular industrial deposits. The present study aimed to evaluate liver disease
      prevalence and potential associated risk factors in four of the Estuary's areas
      (Piloes and Agua-Fria, Cubatao Center, Continental Sao Vicente, and Guaruja) and
      a reference area (Bertioga). This study consisted of a cross-sectional study
      design, in which a questionnaire was used to collect information in 820
      households at each of the study areas. The proportion of total liver diseases,
      hepatitis, cirrhosis, and cancer (liver, biliary tract, and pancreas) per area
      were estimated. Pearson's chi-square test and two proportion differences test
      were applied in order to evaluate associations between disease occurrence and
      areas and to test differences between two proportions, respectively. Single and
      multiple logistic regression models were applied to assess associations between
      disease prevalence and the different study areas. Liver disease prevalence was
      1.5 % among all inhabitants and 1.4 % among those without any type of exposure.
      Among those who reported the presence of liver disease, a higher percentage of
      the participants that reported hepatitis (27.7 %) or other liver disease (48.7 %)
      did not report occupational or alcohol exposures. Hepatitis (77.8 %) was the most
      reported disease, and a statistical association between living in Piloes and Agua
      Fria and the occurrence of hepatitis was observed (Pearson's chi (2): z = 18.1; p
      = 0.001). The consumption of locally-produced groceries (2.88; CI: 1.24-6.70) and
      water (5.88; CI: 2.24-15.45) were shown to be risk factors for the occurrence of
      liver disease. Thus, environmental exposure is still a public health problem
      present in the estuary region.

PMID- 24870290
TI  - Highly active photocatalytic coatings prepared by a low-temperature method.
AB  - Photocatalytic properties of titanium (IV) oxide (TiO2) in anatase form can be
      used for various purposes, including photocatalytic purification of water. For
      such an application, suspended or fixed photocatalytic reactors are used. Those
      with fixed phase seem to be preferred due to some advantages, one of which is the
      avoidance of photocatalyst filtration. To avoid leaching and exfoliation of the
      fixed phase, an immobilization procedure leading to a good adhesion of a catalyst
      to a substrate is crucial. Within this work, we present physical and
      photocatalytic characterization results of five commercially available TiO2
      photocatalysts (P25, P90, PC500, KRONOClean 7000, VPC-10) and one pigment
      (Hombitan LO-CR-S-M), which were successfully immobilized on glass slides by a
      "sol suspension" procedure. Different mechanical tests and characterization
      methods were used to evaluate the stability and morphology of the layers.
      Evaluation of photocatalytic activity was done by tests under UVA and UV-vis
      irradiation, using a method based on the detection of the fluorescent oxidation
      product of terephthalic acid (TPA), i.e., hydroxyterephthalic acid (HTPA).
      Aeroxide(r) P90 incorporated into the silica-titania binder was the most
      photocatalytically active layer and, unlike the others, showed significant
      increase of photocatalytic activity through the entire range of tested UVA
      irradiation intensities (2.3 mW/cm(2)-6.1 mW/cm(2)). The high mechanical
      stability of some photocatalytic layers allows using them in water photocatalytic
      purification reactions.

PMID- 24870291
TI  - Assessment of heavy metal and organic contaminants levels along the Libyan coast
      using transplanted mussels (Mytilus galloprovincialis).
AB  - Within the framework of the MYTIOR project in 2009, heavy metals and organic
      compounds contaminations were assessed in transplanted mussels in 16 different
      stations along the coasts of Libya. These stations were located at miles offshore
      industrial/urban sources but in open sea providing original results related to
      the background contamination rather than linked to a specific coastal source of
      pollutants. Results indicated mercury (Hg, 0.045-0.066 mg/kg dry weight (dw)),
      lead (Pb, 0.44-0, 71 mg/kg dw) and copper (Cu, 3.56-4.21 mg/kg dw) were in the
      same range or at lower value than control for all stations. Chromium (Cr) in
      Meleta (3.08 mg/kg dw) and Bomba (3.80 mg/kg dw) and Cadmium values in all
      stations (1.21-2.41 mg/kg dw) were above control. Meleta, stations from the gulf
      of Syrt and the three eastern stations were the most affected stations by nickel
      (max at 5.83 mg/kg dw in Syrt) when zinc was in the same range (141-197 mg/kg dw)
      and above the control (92 mg/kg dw) at all stations. Polycyclic aromatic
      hydrocarbon (PAH) levels were found in the range of 16.8-42.8 mg/kg (dry weight)
      indicating low levels along the Libyan coast with acenaphthene and benzo (a, b,
      k) pyrenes detected mainly in western Libya. The study of PAH ratios indicated a
      mixed petrogenic/pyrolytic origin. The only polychlorinated biphenyls (PCBs)
      found in Libya were PCB 101 in one location and PCB 153 in Tripoli, Garrapoli,
      Syrt, Ras Lanuf and Benghazi (1.2-1.9 MUg/kg dw). Insecticides were lower than
      control in all stations except DDT, only detected in Misratah (3.5 MUg/kg dw).
      Overall, the results indicated a low background contamination and a low pollution
      extent according to the environmental pressure occurring offshore the Libyan
      coast.

PMID- 24870292
TI  - National collegiate athletic association injury surveillance system: review of
      methods for 2004-2005 through 2013-2014 data collection.
AB  - BACKGROUND: Since 1982, the National Collegiate Athletic Association has used the
      Injury Surveillance System (ISS) to collect injury and athlete-exposure data from
      a representative sample of collegiate institutions and sports. At the start of
      the 2004-2005 academic year, a Web-based ISS replaced the paper-based platform
      previously used for reporting injuries and exposures. OBJECTIVE: To describe the
      methods of the Web-based National Collegiate Athletic Association ISS for data
      collection as implemented from the 2004-2005 to 2013-2014 academic years.
      DESCRIPTION: The Web-based ISS monitored National Collegiate Athletic Association
      sanctioned practices and competitions, the number of participating student
      athletes, and time-loss injuries during the preseason, regular season, and
      postseason in 25 collegiate sports. Starting in the 2009-2010 academic year, non
      time-loss injuries were also tracked. Efforts were made to better integrate ISS
      data collection into the workflow of collegiate athletic trainers. Data for the
      2004-2005 to 2013-2014 academic years are available to researchers through a
      standardized application process available at the Datalys Center Web site.
      CONCLUSIONS: As of February 2014, more than 1 dozen data sets have been provided
      to researchers. The Datalys Center encourages applications for access to the
      data.

PMID- 24870293
TI  - Washington State's Lystedt law in concussion documentation in Seattle public high
      schools.
AB  - CONTEXT: The Lystedt law requires high school athletes who have sustained a
      concussion to be removed from practice and play and not to be allowed to return
      until cleared by a medical professional. OBJECTIVE: To determine the effect of
      the Lystedt law on injury and concussion documentation in the Seattle public high
      schools. DESIGN: Cross-sectional study. SETTING: Seattle public high schools.
      PATIENTS OR OTHER PARTICIPANTS: The numbers of students, aged 13 to 19 years in
      the 2008-2009, 2009-2010, and 2010-2011 school years, were 4348, 4925, and 4806,
      respectively. MAIN OUTCOME MEASURE(S): All injuries documented in SportsWare by
      athletic trainers in Seattle public high schools. We evaluated all injuries,
      including concussions recorded during the 2008-2009 school year, before the
      Lystedt law, and during the 2 school years after the law took effect (2009-2010
      and 2010-2011). Incidence rates before and after the law were estimated and
      compared. RESULTS: The concussion rate was -1.09% in 2008-2009, 2.26% in 2009
      2010, and 2.26% in 2010-2011. A comparison of relative risks showed that the
      incidence rates of concussions were different before and 1 year after the Lystedt
      law (relative risk = 2.10; 95% confidence interval [CI] = 1.50, 2.93) and 2 years
      after the law (relative risk = 2.10; 95% CI = 1.49, 2.93). Overall, the mean
      number of days out of play after 2008-2009 was almost 7 days greater after the
      law took effect (difference = 6.9 days; 95% CI = 0.70, 13.1). For females, the
      mean number of days out of play after 2008-2009 was more than 17 days in 2009
      2010 (difference = 17.2 days; 95% CI = 4.81, 29.5) and was more than 6 days in
      2010-2011 (difference = 6.3 days; 95% CI = 1.62, 11.0). CONCLUSIONS: The number
      of documented concussions more than doubled after the institution of the Lystedt
      law, which may be attributed to heightened awareness and closer monitoring.

PMID- 24870295
TI  - Mucosal melanoma: correlation of clinicopathologic, prognostic, and molecular
      features.
AB  - Although the presence of the t(12;22)(q13;q12) translocation (the defining
      molecular feature of malignant melanoma of soft parts/clear cell sarcoma) in
      cutaneous melanoma has been investigated, no large-scale studies have been
      performed among mucosal melanoma (MucM). In this study we assessed the prevalence
      of the EWSR1 rearrangement in primary MucM, and analyzed gross and microscopic
      features with their potential impact on diagnosis and prognosis. Overall, 132
      specimens from 84 patients were included. A total of 55 cases had an intramucosal
      component. Survival of MucMs of the head and neck was associated with two
      independent factors: size and histology. Tumors more than 3 cm in greatest
      dimension had an average survival of 12.75 months; those 3 cm or less had an
      average survival of 38.3 months (P=0.035). Purely epithelioid tumors had an
      average worse survival of 16.8 months (P=0.028). A cut-off value of 1 mm for
      Breslow depth provided a statistically significant difference in survival at both
      3 and 5 years (P=-0.02) by multivariate analysis in the gynecologic tract. At the
      molecular level three cases had a EWSR1 rearrangement by fluorescent in-situ
      hybridization, but only one with an intramucosal component. None of the 58 cases
      tested by PCR showed the presence of the EWSR1 rearrangement. With the exception
      of vulvar melanomas, the prognosis of mucosal-associated melanomas was poor and
      there was a suggestion that spindle morphology may be more favorable. Our study
      also showed that the EWSR1 rearrangement was very uncommon among MucM. Though
      'clear cell sarcoma' is embedded in the sarcoma literature, the synonym 'melanoma
      of soft parts' has considerable justification in light of our evolving
      understanding of the molecular genetics in the family of malignant melanomas. 

PMID- 24870294
TI  - Frequency of fish intake and diabetes among adult Indians.
AB  - OBJECTIVES: Recent studies have shown that the choice of foods plays a role in
      diabetes prevention. However, little empirical evidence on this association
      exists in developing countries. We aimed to examine the association between
      frequency of fish intake and self-reported diabetes status among adult men and
      women in India. METHODS: Analysis of cross-sectional data from participants in
      India's third National Family Health Survey conducted during 2005-2006 was
      performed. Associations between fish intake, determined by frequency of
      consumption (daily, weekly, occasionally, and never), and self-reported diabetes
      were estimated using multivariable-adjusted models in 99,574 women, 56,742 men,
      and 39,257 couples aged 20-49 years after adjusting for frequency of consumption
      of other food items, body mass index (BMI) status, tobacco smoking, alcohol
      drinking, watching television, age, education, living standard of the household,
      and place of residence. RESULTS: After adjustment for other dietary, lifestyle,
      and socioeconomic and demographic characteristics, odds of diabetes were 2 times
      higher (odds ratio [OR]: 2.02; 95% confidence interval [CI], 1.59-2.57; p <
      0.0001) among those who reported consuming fish daily compared to those who never
      consumed fish. Weekly fish intake was also associated with a higher odds of
      having diabetes (OR: 1.55; 95% CI, 1.25-1.93; p < 0.0001). The adjusted effect of
      daily fish intake on diabetes was greater among men (OR: 2.46; 95% CI, 1.66-3.65)
      than among women (OR: 1.72; 95% CI, 1.26-2.33). In cross-spousal sensitivity
      analysis, the odds of a husband having diabetes was also associated with wife's
      daily/weekly consumption of fish (OR: 1.36; 95% CI, 0.92-2.01) and the odds of a
      wife having diabetes was also associated with husband's daily/weekly consumption
      of fish (OR: 1.21; 95% CI, 0.87-1.68). CONCLUSIONS: In a large nationally
      representative sample of adult men and women in India, daily or weekly fish
      intake was positively associated with the presence of diabetes. However, this is
      an observational finding and uncontrolled confounding cannot be excluded as an
      explanation for the association. More epidemiological research with better
      measures of food intake and clinical measures of diabetes is needed in a
      developing country setting to validate the findings.

PMID- 24870296
TI  - A macrocyclic chelator with unprecedented Th4+ affinity.
AB  - A novel macrocyclic octadentate ligand incorporating terephthalamide binding
      units has been synthesized and evaluated for the chelation of Th(4+). The thorium
      complex was structurally characterized by X-ray diffraction and in solution with
      kinetic studies and spectrophotometric titrations. Dye displacement kinetic
      studies show that the ligand is a much more rapid chelator of Th(4+) than
      prevailing ligands (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid and
      diethylenetriaminepentaacetic acid). Furthermore, the resulting complex was found
      to have a remarkably high thermodynamic stability, with a formation constant of
      10(54). These data support potential radiotherapeutic applications. 

PMID- 24870297
TI  - Magnetic force microscopy investigation of arrays of nickel nanowires and
      nanotubes.
AB  - The magnetic properties of arrays of nanowires (NWs) and nanotubes (NTs), 150 nm
      in diameter, electrodeposited inside nanoporous polycarbonate membranes are
      investigated. The comparison of the nanoscopic magnetic force microscopy (MFM)
      imaging and the macroscopic behavior as measured by alternating gradient force
      magnetometry (AGFM) is made. It is shown that MFM is a complementary technique
      that provides an understanding of the magnetization reversal characteristics at
      the microscopic scale of individual nanostructures. The local hysteresis loops
      have been extracted by MFM measurements. The influence of the shape of such
      elongated nanostructures on the dipolar coupling and consequently on the
      squareness of the hysteresis curves is demonstrated. It is shown that the
      nanowires exhibit stronger magnetic interactions than nanotubes. The non
      uniformity of the magnetization states is also revealed by combining the MFM and
      AGFM measurements.

PMID- 24870299
TI  - Differential diagnosis of colorectal polyps with narrow band imaging colonoscopy
      without magnification.
AB  - BACKGROUND/AIMS: Narrow band imaging (NBI) endoscopy can be used for gross
      differentiation between the types of colonic polyps. This study was conducted as
      a retrospective study for estimation of the interobserver and intra-observer
      agreement of the pit pattern of the mucosal surface and the accuracy of histology
      prediction. METHODS: A total of 159 patients underwent complete colonoscopy and
      219 polyps examined by NBI endoscopy without magnification were assessed.
      Interobserver and intra-observer agreement were calculated by investigators in
      each group for determination of the surface pattern and prediction of histology
      based on the modified Kudo's classification using intraclass correlation
      coefficient. RESULTS: Interobserver agreement for the surface pit pattern and
      prediction of polyp type was 0.84 and 0.73 in experienced endoscopists, and 0.86
      and 0.62 in trainees, respectively. Intra-observer agreement for the surface pit
      patterns and prediction of polyp type was 0.81, 0.83, 0.85, 0.83, 0.56, 0.84,
      0.51, 0.83, and 0.71; and 0.71, 0.70, 0.82, 0.54, 0.72, 0.37, 0.51, 0.34, and
      0.30, respectively. The diagnostic accuracy for prediction of polyp type was
      69.4% for experienced endoscopists and 72.9% for trainees. CONCLUSIONS: NBI
      endoscopy without magnification showed fairly good inter and intra-observer
      agreement for the pit pattern of the mucosal surface and the accuracy of
      histology prediction; however, it had some limitation for differentiation of
      colon polyp histologic type. Training and experience with NBI is needed for
      improvement of accuracy.

PMID- 24870298
TI  - The evolution of bowel preparation and new developments.
AB  - Bowel preparation is essential for successful colonoscopy examination, and the
      most important factor is the bowel preparation agent used. However, selection of
      a bowel preparation agent invariably involves compromise. Originally, bowel
      preparation was performed for radiologic and surgical purposes, when the process
      involved dietary limitations, cathartics, and enemas, which had many side
      effects. Development of polyethylene glycol (PEG) solution led to substantive
      advancement of bowel preparation; however, despite its effectiveness and safety,
      the large volume involved, and its salty taste and unpleasant odor reduce
      compliance. Accordingly, modified PEG solutions requiring consumption of lower
      volumes and sulfate-free solutions were developed. Aqueous sodium phosphate is
      more effective and better tolerated than PEG solutions; however, fatal
      complications have occurred due to water and electrolyte shifts. Therefore,
      aqueous sodium phosphate was withdrawn by the US Food and Drug Administration,
      and currently, only sodium phosphate tablets remain available. In addition, oral
      sulfate solution and sodium picosulfate/magnesium citrate are also available, and
      various studies have reported on adjunctive preparations, such as hyperosmolar or
      stimulant laxatives, antiemetics, and prokinetics, which are now in various
      stages of development.

PMID- 24870300
TI  - Risk factors of recurrent ischemic colitis: a multicenter retrospective study.
AB  - BACKGROUND/AIMS: Recurrence of ischemic colitis (IC) has not been studied
      extensively. The aim of this study was to investigate the characteristics of
      recurrent IC in the community setting and to identify any risk factors. METHODS:
      We conducted a retrospective study in two community hospitals. Medical records of
      patients with IC from January 2007 to January 2013 were reviewed. Demographic
      details, clinical features, co- morbidities, concomitant use of
      medications,laboratory studies, imaging findings, endoscopic and histological
      features, surgery, hospital stay, and death within 30 days were collected.
      Patients were divided into two groups (recurrent IC group, non-recurrent IC
      group). RESULTS: A total of 118 patients with IC were identified. IC recurred in
      10 patients (8.5%) during the study period. Half of the patients in the recurrent
      IC group were current smokers as compared to only 18.7% of patients in the non
      recurrent group. In the recurrent IC group, 20.0% of patients never smoked as
      compared to 61.7% in the non-recurrent group (p=0.027).Abdominal aortic aneurysm
      (AAA) was more frequent in the recurrent IC group (40.0% vs. 4.7%; p=0.003). No
      differences in other clinical symptoms, CT scan findings, comorbidities,
      endoscopic features, or use of concomitant medications were observed between the
      two groups. The need for surgical intervention, blood transfusion, intensive care
      unit stay, mechanical ventilation,length of hospital stay, and anatomic location
      of affected segments did not differ between the two groups. CONCLUSIONS: IC
      recurred in 8.5% of patients during the six-year study period. Current smoking
      status and presence of AAA were identifying risk factors for recurrence of IC.

PMID- 24870301
TI  - [Clinical features of non-alcoholic fatty liver disease in cryptogenic
      hepatocellular carcinoma].
AB  - BACKGROUND/AIMS: Nonalcoholic fatty liver disease (NAFLD) may be one of the
      important causes of cryptogenic hepatocellular carcinoma (HCC). The aim of this
      study was to evaluate whether patients with cryptogenic HCC share clinical
      features similar to that of NAFLD. METHODS: Cryptogenic HCC was defined as HCC
      that occurs in patients with the following conditions: HBsAg(-), anti-HCV(-), and
      alcohol ingestion of less than 20 g/day. All patients diagnosed with cryptogenic
      HCC from 2005 to 2012 (cryptogenic HCC group), and all patients diagnosed with
      HBV associated HCC between 2008 and 2012 (HBV-HCC group) were enrolled in the
      present study. Clinical features, BMI, lipid profiles, presence of diabetes
      mellitus, hypertension, and metabolic syndrome were compared between the two
      groups. RESULTS: Cryptogenic HCC group was composed of 35 patients (19 males and
      16 females) with a mean age of 70 +/- 11 years. HBV-HCC group was composed of 406
      patients (318 males and 88 females) with a mean age of 56 +/- 7 years. Patients
      in the cryptogenic HCC group were older (p=0.001) and female dominant (p=0.042)
      than those in the HBV-HCC group. There were no differences in the laboratory test
      results including lipid profiles and Child-Turcotte-Pugh class between the two
      groups. Patients in the cryptogenic HCC group had higher prevalence of diabetes
      (37% vs. 17%, p=0.015), hypertension (49% vs.27%, p=0.051), metabolic syndrome
      (37% vs. 16%, p=0.001), and higher BMI (25.3 kg/m(2) vs. 24.1 kg/m(2), p=0.042)
      than those in the HBV- HCC group. The tumor stage was more advanced (stage III
      and IV) at diagnosis in the cryptogenic HCC group than in the HBV-HCC group (60%
      vs. 37%, p=0.007). CONCLUSIONS: Cryptogenic HCC has clinical features similar to
      that of NAFLD and is diagnosed at a more advanced tumor stage.

PMID- 24870302
TI  - Changes in causative pathogens of acute cholangitis and their antimicrobial
      susceptibility over a period of 6 years.
AB  - BACKGROUND/AIMS: We evaluated changes of causative pathogen in acute cholangitis
      and their antimicrobial susceptibility over six years and differences between
      community-acquired and hospital-acquired acute cholangitis at our institution.
      METHODS: Medical records of 1,596 patients with acute cholangitis and biliary
      drainage between August 2006 and August 2012 were reviewed retrospectively. Cases
      were divided according to time: period 1 (August 2006-December 2008, n=645,
      40.4%), period 2 (January 2009-August 2012, n=951, 59.6%). Cases were divided
      according to community-acquired cholangitis (n=1,397, 87.5%) and hospital
      acquired cholangitis (n=199, 12.5%). Causative pathogens and antimicrobial
      susceptibility were investigated in each group. RESULTS: Causative pathogen was
      isolated from bile culture in 1,520 out of 1,596 cases (95.2%). The three most
      frequently isolated Gram-negative bacteria were extended-spectrum beta-lactamase
      (ESBL)-producing Escherichia coli (n=485, 30.4%), E. coli (n=237, 13.2%), and
      Citrobacter freundii (n=110, 6.9%). Between periods 1 and 2, prevalence of ESBL
      producing E. coli and Klebsiella pneumoniae did not show significant change
      (36.7% vs. 32.1%, p=0.073; 6.6% vs. 6.2%, p=0.732). C. freundii showed a
      significant increase from period 1 to period 2 (1.7% vs. 13.2%, p=0.000). In both
      time periods, imipenem was the antimicrobial agent showing the highest rate of
      susceptibility (93.3% vs. 93.9%, p=0.783). Higher prevalence of ESBL-producing E.
      coli and C. freundii was observed in the hospital-acquired cholangitis group
      (52.1% vs. 31.2%, p=0.000; 15.9% vs. 7.3%, p=0.001). CONCLUSIONS: The most common
      causative pathogen of acute cholangitis was ESBL-producing E. coli. Prevalence of
      C. freundii increased over the time period. Imipenem should be reserved as an
      alternative for resistant pathogens.

PMID- 24870303
TI  - A case of late onset-acute tubulointerstitial nephritis with infliximab and
      mesalazine treatment in a patient with Crohn's disease.
AB  - Infliximab is a chimeric anti-tumor necrosis factor-alpha monoclonal antibody.
      Infusion related reactions and infection are well known side effects of
      infliximab; however, renal complications have not been well recognized. We report
      on a patient with late onset-acute tubulointerstitial nephritis (ATIN) after
      treatment with infliximab and mesalazine for Crohn's disease. A 25-year-old woman
      was admitted with a purpuric rash on both lower extremities and arthralgia. She
      had been diagnosed with Crohn's disease 5.6 years previously and had been treated
      with mesalazine and infliximab. Serum creatinine level, last measured one year
      ago, was elevated from 0.6 mg/dL to 1.9 mg/dL. Results of urinalysis, ultrasound,
      and serologic examinations were normal. With a tentative diagnosis of Henoch
      Schonlein purpura, oral prednisolone was given, and serum creatinine decreased to
      1.46 mg/dL, but was elevated to 2.6 mg/dL again at two months after
      discontinuation of prednisolone. Renal biopsy indicated that ATIN was probably
      induced by drug, considering significant infiltration of eosinophils. Concomitant
      use of infliximab with mesalazine was supposed to trigger ATIN. Oral prednisolone
      was administered, and serum creatinine level showed partial recovery. Thus, ATIN
      should be suspected as a cause of renal impairment in Crohn's disease even after
      a long period of maintenance treatment with infliximab and mesalazine.

PMID- 24870304
TI  - Mesocolon laceration following colonoscopy.
AB  - Colonoscopic examination is a safe procedure, however, unexpected complications
      can sometimes occur. Bleeding and perforation of the colon have been reported as
      the most common complications. Hemoperitoneum after colonoscopy is an unusual
      complication, but it may be catastrophic. We report on a 20-year-old man who
      experienced left low quadrant pain after undergoing colonoscopy. Hemoperitoneum
      was diagnosed using abdominal CT. A laparoscopic exploration was urgently
      performed, revealing a lacerated mesocolon of the descending colon. Bleeding of
      the injured site was controlled without complication. The patient recovered fully
      without signs of recurrent bleeding. This report implies that if the patient has
      persistent abdominal pain after undergoing colonoscopy, we should consider
      hemoperitoneum as one of the causes. To the best of our knowledge, no case of
      isolated laceration of the mesocolon of the descending colon after colonoscopy
      has been reported.

PMID- 24870305
TI  - Solitary extramedullary plasmacytoma in the gastrointestinal tract: report of two
      cases and review of literature.
AB  - Solitary extramedullary plasmacytoma (EMP) is a plasma cell neoplasm without bone
      marrow involvement. EMPs are rare in the gastrointestinal (GI) tract. We report
      two cases of primary EMP, one in the transverse colon and the other in the
      stomach. In the first case, a mass on the transverse colon was found on
      colonoscopy. The patient underwent left hemicolectomy and has been followed-up
      for 3 years without recurrence postoperatively. The latter case had several
      masses in the stomach. The patient underwent bypass surgery and has received
      supportive care for 1 month. Histopathologic specimens of both the cases showed a
      monoclonal lambda chain EMP. Subsequent investigations included a bone marrow
      biopsy, serum IgA, IgG, IgM and serum protein electrophoresis, and the results
      were negative for multiple myeloma in both the cases. Solitary EMP in the GI
      tract can be mistaken for colon cancer or stomach cancer on endoscopy; therefore,
      a sufficient number of biopsy specimens can help diagnose solitary EMPs. Surgical
      resection alone or with radiation therapy in cases with positive surgical margin
      is currently the only treatment for solitary EMP in the GI tract. Further study
      is necessary to determine disease prognosis and to investigate other treatment
      methods.

PMID- 24870306
TI  - [Disappearance of intrahepatic bile duct hepatocellular carcinoma after
      endoscopic retrograde cholangiopancreatography and transarterial chemoinfusion: a
      case report].
AB  - Invasion of the bile duct by hepatocellular carcinoma (HCC), which is called
      intrahepatic bile duct HCC, is rare and has a poor prognosis. Early diagnosis and
      surgical resection is important for treatment. A 58-year-old man who underwent
      hepatic resection for HCC 4 years ago and received transarterial
      chemoembolization (TACE) 2 years after the operation for recurred HCC presented
      with jaundice. CT scan revealed a tumor in the common bile duct without
      intrahepatic lesion. Therefore, ERCP was done to perform biopsy and biliary
      drainage. Histological examination was compatible with hepatocellular carcinoma.
      However, the tumor could not be visualized at angiography and thus, only
      transarterial chemoinfusion was performed without embolization. The tumor had
      disappeared on follow-up CT scan, and the patient has been disease free for 23
      months without evidence of recurrence. Herein, we report a case of intrahepatic
      bile duct HCC which disappeared after ERCP.

PMID- 24870307
TI  - Variation in labor induction over the days of the week.
AB  - OBJECTIVE: To quantify the variation in induction of labor (IOL) over the days of
      the week for gravid women in the United States. STUDY DESIGN: Women who delivered
      singletons between 24 and 42 weeks' gestation were identified using birth
      certificate data from 2007 to 2010. Women with pregnancy-associated hypertension,
      fetal anomalies, previous cesarean delivery, or incomplete records were excluded.
      The primary outcome was IOL. Women were stratified into four gestational age
      groups: < 34, 34 to 36, 37 to 38, and >= 39 weeks. Frequencies of IOL were
      determined according to day of the week. Multivariable logistic regression
      estimated the association between weekend delivery and IOL, adjusting for
      maternal characteristics and year of delivery. RESULTS: There were 11.6 million
      eligible women. For each gestational age stratum, the frequency of IOL was
      increased on weekdays compared with weekends (8.0 vs. 7.4%, 16.5 vs. 13.2%, 25.0
      vs. 14.8%, and 33.2 vs. 19.3% at < 34, 34-36, 37-38, and >= 39 weeks,
      respectively; p < 0.01 for all). Multivariable analyses demonstrated that weekend
      IOL was inversely related to gestational age (odds ratios: 0.93, 0.77, 0.52, and
      0.48, respectively; p < 0.001 for all). CONCLUSION: The frequency of IOL varies
      according to the day of the week, with the odds of weekend IOL lowest at greater
      gestational ages.

PMID- 24870308
TI  - The role of the reduction of spiral artery remodeling and heme oxygenase 1 in
      mediating AT1-AA-induced hypertension and intrauterine growth restriction in
      pregnant rats.
AB  - INTRODUCTION: Recently, emerging evidence has indicated that preeclamptic women
      who have angiotensin receptor agonistic autoantibodies (AT1-AA), these antibodies
      contribute to features of the disease. AIM: The purpose of this study was to
      determine the role of spiral artery remodeling in mediating AT1-AA-induced
      hypertension and intrauterine growth restriction in pregnant rats. We
      hypothesized that AT1-AA-mediated heme oxygenase 1 (HO-1) reduction contributes
      to decreased spiral artery remodeling. Rat AT1-AA and an HO-1 inducer were
      administered to pregnant rats. RESULT: Mean arterial pressure (MAP) increased
      from 98 +/- 4 mm Hg in normal pregnant rats to 113 +/- 6 mm Hg in AT1-AA-infused
      rats (p < 0.05), which was significantly attenuated by the HO-1 inducer (103 +/-
      2 mm Hg). Fetal weight was also attenuated by HO-1 inducer, and kidney and liver
      development was adversely affected. Spiral artery remodeling was significantly
      reduced in AT1-AA-treated pregnant rats compared with that in normal pregnant
      rats, and this was significantly ameliorated by an HO-1 inducer. CONCLUSION: Our
      findings demonstrate that AT1-AA-mediated HO-1 reduction contributes to reduced
      spiral artery remodeling, and is one mechanism whereby AT1-AA mediates
      hypertension and intrauterine growth retardation.

PMID- 24870309
TI  - Roles of small laccases from Streptomyces in lignin degradation.
AB  - Laccases (EC 1.10.3.2) are multicopper oxidases that can oxidize a range of
      substrates, including phenols, aromatic amines, and nonphenolic substrates. To
      investigate the involvement of the small Streptomyces laccases in lignin
      degradation, we generated acid-precipitable polymeric lignin obtained in the
      presence of wild-type Streptomyces coelicolor A3(2) (SCWT) and its laccase-less
      mutant (SCDeltaLAC) in the presence of Miscanthus x giganteus lignocellulose. The
      results showed that strain SCDeltaLAC was inefficient in degrading lignin
      compared to strain SCWT, thereby supporting the importance of laccase for lignin
      degradation by S. coelicolor A3(2). We also studied the lignin degradation
      activity of laccases from S. coelicolor A3(2), Streptomyces lividans TK24,
      Streptomyces viridosporus T7A, and Amycolatopsis sp. 75iv2 using both lignin
      model compounds and ethanosolv lignin. All four laccases degraded a phenolic
      model compound (LM-OH) but were able to oxidize a nonphenolic model compound only
      in the presence of redox mediators. Their activities are highest at pH 8.0 with a
      low krel/Kapp for LM-OH, suggesting that the enzymes' natural substrates must be
      different in shape or chemical nature. Crystal structures of the laccases from S.
      viridosporus T7A (SVLAC) and Amycolatopsis sp. 75iv2 were determined both with
      and without bound substrate. This is the first report of a crystal structure for
      any laccase bound to a nonphenolic beta-O-4 lignin model compound. An additional
      zinc metal binding site in SVLAC was also identified. The ability to oxidize
      and/or rearrange ethanosolv lignin provides further evidence of the utility of
      laccase activity for lignin degradation and/or modification.

PMID- 24870310
TI  - Sugar additives improve signal fidelity for implementing two-phase resorufin
      based enzyme immunoassays.
AB  - Enzymatic signal amplification based on fluorogenic substrates is commonly used
      for immunoassays; however, when transitioning these assays to a digital format in
      water-in-mineral oil emulsions, such amplification methods have been limited by
      the leakage of small reporting fluorescent probes. In the present study, we used
      a microfluidic system to study leakage from aqueous droplets in a controlled
      manner and confirmed that the leakage of fluorescent resorufin derivatives is
      mostly due to the presence of the lipophilic surfactant Span80, which is commonly
      used to preserve emulsion stability. This leakage can be overcome by the addition
      of specific sugars that most strongly interfered with the surfactants ability to
      form micelles in water. The application of the microfluidic system to the
      quantitative analysis of droplets and the implementation of the described sugar
      additives would allow for alternatives to fluorinated surfactant-based platforms
      and improve the signal fidelity in enzyme immunoassays implemented through
      multiphase microfluidics. 

PMID- 24870311
TI  - Systematics of the Podarcis hispanicus complex (Sauria, Lacertidae) III: valid
      nomina of the western and central Iberian forms.
AB  - Recent genetic works have suggested that the Iberian wall lizard Podarcis
      hispanicus (Steindachner, 1870) sensu lato is a species complex. Several forms
      have already been elevated to species rank and linked to available nomina, but at
      least three still have to be formally named, including the western Iberian forms
      currently designated as Podarcis hispanicus "type 1A", "type 1B" and "type 2".
      The aim of the present work is to assign a valid nomen to these taxa. Using
      multivariate analyses, we first checked that the morphological differences
      reported in Portugal between type 1 and type 2 are maintained over their
      distribution range. We then investigated phenotypic differentiation between type
      1A and type 1B, which were found to be so similar that identification based on
      phenotype is currently not advisable. We propose to treat type 1 and type 2 as
      distinct species because of their level of genetic and phenotypic divergence,
      large area of distribution and ample evidence for reduced or absent introgression
      in contact zones. We maintain type 1A and 1B as subspecies for the time being,
      pending further analyses of their contact zone. The valid nomen for "Podarcis
      hispanica type 1 (sensu lato)" is Lacerta muralis guadarramae Bosca, 1916 which
      becomes Podarcis guadarramae (Bosca, 1916). Lineage type 1A is here described as
      a new taxon: P. guadarramae lusitanicus ssp. nov., inhabiting northern Portugal
      and northwestern Spain. The type 1B lineage corresponds to the nominotypical
      subspecies that inhabits Spain, mostly the Central Iberian Mountains. We were
      unable to locate an available nomen for "Podarcis hispanica type 2", which is
      here described as Podarcis virescens sp. nov. This species is widely distributed
      in the plains and plateaus of central and parts of south-western Spain as well as
      central and southern Portugal. 

PMID- 24870312
TI  - Differentiation among cave populations of the Eukoenenia spelaea species-complex
      (Arachnida: Palpigradi) in the southwestern Alps.
AB  - Current knowledge of the taxonomy and distribution of European cave palpigrades
      largely rests upon incidental records. Samples seldom comprise more than one or
      two specimens, and many regions have only been unevenly explored, if at all. The
      present study is the first to investigate morphological variability within, and
      differentiation between, subterranean palpigrade populations in a small,
      geographically coherent area. It is based on relatively abundant material from
      six localities in the SW Alps (Piedmont, Italy) and two non-Italian comparative
      localities. Discrete and continuous characters reveal, on the one hand, a close
      grouping within the Eukoenenia spelaea species-complex, and, on the other hand, a
      remarkable short-range endemism. The occurrence of five distinct morphologies in
      a SW Alpine area of just 2000 square kilometres or so indicates that subterranean
      biodiversity parallels the rich above-ground biodiversity there. The Cottian Alps
      in the North harbour E. roscia Christian sp. n., E. lanai Christian sp. n. and
      the widespread E. spelaea. Two caves in the Maritime and Ligurian Alps are
      populated by E. bonadonai, which was originally described from the Provence Alps,
      while the Bossea cave in the Ligurian Alps remains the only known locality for E.
      strinatii. We evaluate the traditionally employed morphological characters and
      those recently proposed for use in Eukoenenia systematics. Further, we provide
      data on the formerly undescribed females of E. strinatii and E. bonadonai, and
      provide comprehensive pictorial information on the SW Alpine cave palpigrades to
      set new benchmarks for the taxonomy of the E. spelaea species-complex. 

PMID- 24870313
TI  - Silbermann's "Revue entomologique": publication dates for nomenclatural purposes
      and bibliographic notes (Insecta, mainly Coleoptera).
AB  - The rare yet entomologically important scientific journal "Revue entomologique"
      was published in French language in five volumes during the first half of the
      nineteenth century. We provide some bibliographic notes which reveal, for
      example, the motivation and goals of the editor, Gustave Silbermann. He wanted to
      contribute to an exchange of entomological knowledge between French and German
      scientists, in particular by translating German articles into French and to
      inform his readers of new German and French entomological literature. The work
      deals with many taxa, mainly beetles, yet also moths, cicadas and other insects.
      The journal contains taxonomic notes and species descriptions for which correct
      dating is essential. Evidence inside the books indicates the partly wrong
      assignment of the publication dates printed on the title pages from 1833 to 1837.
      We found one depository holding the originally assembled and unbound fascicles of
      the first two volumes. Despite the month of publication being absent on all
      wrappers, their original composition allowed the detailed reconstruction of
      publication dates, as well as of unpaginated species descriptions. We analysed
      the work, attributed page numbers to single or merged fascicles and provided
      publication dates for all 30 fascicles, which were shown to have been published
      from 1833 to 1840. We also traced the enigmatic reference for the description of
      a longhorn beetle (Molorchus ulmi Chevrolat, 1838) and were able to demonstrate
      that its supposed association with the "Revue entomologique" is erroneous. 

PMID- 24870314
TI  - A new species of the Miniopterus schreibersii species complex (Chiroptera:
      Miniopteridae) from the Maghreb Region, North Africa.
AB  - We used an integrative approach combining cranio-dental characters, mitochondrial
      and nuclear data and acoustic data to show the presence in the genus Miniopterus
      of a cryptic species from the Maghreb region. This species was previously
      recognised as Miniopterus schreibersii (Kuhl, 1817). Miniopterus maghrebensis sp.
      nov. can be differentiated from M. schreibersii sensu stricto on the basis of
      cranial characters and from mitochondrial DNA and microsatellite evidence.
      Although slight external morphological and acoustic differences were noted
      between the two species, these criteria alone did not allow reliable species
      identification from live animals. Based on the specimens identified
      morphologically and/or genetically, the distribution range of M. maghrebensis sp.
      nov. extends from northern Morocco to south of the High Atlas Mountains and
      northern Tunisia. The new cryptic species is found in sympatry with M.
      schreibersii s.str. near coastal regions of North Africa. 

PMID- 24870315
TI  - Anolis boulengerianus Thominot, 1887, a senior synonym of Anolis isthmicus Fitch,
      1978 (Squamata: Dactyloidae).
AB  - For most of its history, the name Anolis boulengerianus Thominot, 1887 has been
      regarded as a junior synonym of Anolis nebulosus (Wiegmann, 1834) or Anolis
      nebuloides Bocourt, 1873. However, a comparison of the syntypes and additional
      topotypical specimens of A. boulengerianus with three topoparatypes and
      additional specimens of the species currently referred to as Anolis isthmicus
      Fitch, 1978 showed that these two names pertain to the same species. Because of
      the priority principle, A. isthmicus becomes a junior synonym of A.
      boulengerianus. We provide a redescription of the type series of A.
      boulengerianus and an updated diagnosis for this taxon relative to all other beta
      anoles. 

PMID- 24870316
TI  - On the identity of Chironius flavolineatus (Serpentes: Colubridae).
AB  - The snake genus Chironius Fitzinger, 1826 is endemic to the Neotropical region,
      occurring from Honduras to Uruguay and northeastern Argentina. Some species of
      the genus have taxonomic and/or nomenclatural problems, such as C. flavolineatus
      which lacks agreement in the literature about its authorship and type locality.
      Some researchers have been suggesting Jan (1863) as the author of the species
      since he first described C. flavolineatus based on two specimens. However, other
      researchers report that Jan's description is so incomplete that it is not
      possible to ascertain what snake he had in mind and therefore suggest Boettger
      (1885) as the author, since he was the first to provide a detailed description of
      the species. In the present study one of the syntypes of C. flavolineatus,
      supposedly destroyed in Second World War, was found. Thus, the taxonomic identity
      of C. flavolineatus was redefined, its lectotype was designated and the
      authorship of the taxa is attributed to Jan (1863). 

PMID- 24870317
TI  - Illustrated key for identification of the species included in the genus
      Leptoglossus (Hemiptera: Heteroptera: Coreidae: Coreinae: Anisoscelini), and
      descriptions of five new species and new synonyms.
AB  - Five new species of Leptoglossus are described: L.caicosensis from Turks and
      Caicos Island, L. egeri and L. impensus from Bolivia, L. franckei from Costa
      Rica, and L. polychromus from Ecuador, Cooperative Republic of Guiana (British
      Guiana), and French Guiana. Leptoglossus argentinus Bergroth is synonymized under
      L. chilensis chilensis (Spinola) and Narnia anaticula Brailovsky & Barrera under
      Leptoglossus occidentalis Heidemann. Dorsal view drawings and key to the 61 known
      species and 1 subspecies are included; a complete checklist, and the position of
      each species within the species-group defined herein, are given except for two
      species L. macrophylus Stal and L. polychromus sp.nov., that are insertae-sedis.
      The pronotal disk, hind legs, and male genital capsule of the new species here
      described are illustrated. 

PMID- 24870318
TI  - On the identity of two species of Proctophyllodidae (Acari: Astigmata:
      Analgoidea) described by Herbert F. Berla in Brazil, with a description of
      Lamellodectes gen. nov. and a new species.
AB  - Two proctophyllodid species described by Herbert F. Berla were studied, re
      described and their generic status was re-evaluated. A new genus, Lamellodectes
      gen. nov. (Proctophyllodidae: Pterodectinae), is erected to accommodate
      Pterodectes ocelatus Berla, 1960 from the White-collared Foliage-gleaner,
      Anabazenops fuscus (Vieillot) (Furnariidae), and a new species, L. distinctus sp.
      nov., from the Double-collared seedeater, Sporophila caerulescens (Emberizidae).
      Proctophyllodes minor Berla, 1959a is herein transferred to the genus Platyacarus
      Kudon, 1982a (Proctophyllodinae) and given a valid name Platyacarus minor (Berla)
      comb. nov. Updated keys to subfamilies and genera of the family Proctophyllodidae
      are presented. In addition, the known biogeographical distribution for each genus
      is summarized. 

PMID- 24870319
TI  - The genus Palaeagapetus Ulmer (Trichoptera, Hydroptilidae, Ptilocolepinae) in
      North America.
AB  - The genus Palaeagapetus Ulmer (Trichoptera, Hydroptilidae, Ptilocolepinae) is
      revised in North America. Descriptions of the western species, P. nearcticus
      Banks 1938, are provided with the first descriptions of the female, pupa, larva,
      egg and case and with notes on food, habitat and annual life cycle. The male and
      female of the eastern species, P. celsus Ross 1936, are described or redescribed
      with some ecological notes. Distributions of the two species are summarized. 

PMID- 24870320
TI  - Comparative morphology and taxonomy of Sciacharis s. str., Chathamaenus Franz and
      Maorinus Franz (Coleoptera: Staphylinidae: Scydmaeninae).
AB  - Sciacharis s. str. is redefined based on the morphology of its type species, S.
      fulva Broun, and compared with sympatric genera Chathamaenus Franz (endemic to
      New Zealand) and Maorinus Franz (known from New Zealand and Australia). As a
      result, Chathamaenus is placed as a junior synonym of Sciacharis s. str., and
      Maorinus, originally described as a subgenus of Euconnus Thomson (under a
      preoccupied name Maoria Franz), subsequently elevated in rank, is here reduced to
      a subgenus of Sciacharis. Forty six new combinations resulted from this action
      are listed and Sciacharis (Maorinus) rakiuraensis nom. n. is proposed as a
      replacement name for Euconnus australis Franz, 1975, a junior primary homonym of
      Euconnus australis Franz, 1967. 

PMID- 24870321
TI  - New species and new records of mites of the genus Stigmaeus(Acari: Prostigmata:
      Stigmaeidae) from Crimea.
AB  - Three new species of the genus Stigmaeus Koch, 1836 (Acari: Stigmaeidae) are
      described from various habitats in Crimea: Stigmaeus kuznetsovi sp. nov. from
      nests of Microtus socialis (Rodentia: Cricetidae); S. mitrofanovi sp. nov. from
      galleries of Pityogenes bistridentatus (Coleoptera: Curculionidae) under the bark
      of Pinus pallasiana, and S. silvestris sp. nov. from rotten log of Pinus
      pallasiana. Stigmaeus corticeus Kuznetsov and Wainstein, 1977 and S.
      maraghehiensis Bagheri and Ueckermann, 2012 are recorded for the first time in
      Crimea. A key to species of the genus Stigmaeus of Crimea is provided. 

PMID- 24870322
TI  - The phylogenetic position of the Critically Endangered Saint Croix ground lizard
      Ameiva polops: revisiting molecular systematics of West Indian Ameiva.
AB  - The phylogenetic position of the critically endangered Saint Croix ground lizard
      Ameiva polops is presently unknown and several hypotheses have been proposed. We
      investigated the phylogenetic position of this species using molecular
      phylogenetic methods. We obtained sequences of DNA fragments of the mitochondrial
      ribosomal genes 12S rDNA and 16S rDNA for this species. We aligned these
      sequences with published sequences of other Ameiva species, which include most of
      the Ameiva species from the West Indies, three Ameiva species from Central
      America and South America, and one from the teiid lizard Tupinambis teguixin,
      which was used as outgroup. We conducted Maximum Likelihood and Bayesian
      phylogenetic analyses. The phylogenetic reconstructions among the different
      methods were very similar, supporting the monophyly of West Indian Ameiva and
      showing within this lineage, a basal polytomy of four clades that are separated
      geographically. Ameiva polops grouped in a cluster that included the other two
      Ameiva species found in the Puerto Rican Bank: A. wetmorei and A. exsul. A sister
      relationship between A. polops and A. wetmorei is suggested by our analyses. We
      compare our results with a previous study on molecular systematics of West Indian
      Ameiva.  

PMID- 24870323
TI  - New records of the caridean shrimp genus Processa Leach, 1815 (Crustacea:
      Decapoda: Processidae) from Japan, with descriptions of two new species.
AB  - Three species of the processid shrimp genus Processa Leach, 1815, including two
      new species, are reported from shallow coastal waters in Okinawa Island, Ryukyu
      Islands, Japan: P. affinis Hayashi, 1975, P. filipes n. sp. and P. hayashii n.
      sp. The present specimens of P. affinis represent the rediscovery and range
      extension of this poorly known species, originally described from Indonesia. Male
      characteristics of P. affinis are documented for the first time. The two new
      species are referred to the P. aequimana Paulson, 1875 species group. Processa
      filipes n. sp. is characteristic in the greatly elongate fifth pereopod and the
      transverse ridge on thoracic sternite 8 consisting of soft cuticle. Processa
      hayashii n. sp. is characterized by the presence of a deep concavity on the
      anterolateral margin of the carapace just inferior to the antennal tooth. The
      number of species of Processa known from Japanese waters is raised from five to
      eight. 

PMID- 24870324
TI  - Gymnancyla (Gymnancyla) iranella (Lepidoptera: Pyralidae, Phycitinae),a new
      species from Iran.
AB  - A full description of Gymnancyla (Gymnancyla) iranella sp. n. is given; adult,
      head and appendages, male and female genitalia and the larva are described and
      illustrated, based on 15 males, 12 females and three last instar larvae collected
      in central Iran, Yazd Province, Abarkuh region. Larvae were found on Salsola sp.
      (family Chenopodiaceae). 

PMID- 24870326
TI  - The genus Ademon Haliday (Hymenoptera: Braconidae: Opiinae) from China, with
      descriptions of two new species.
AB  - The species of Ademon Haliday (Braconidae, Opiiinae) from China are studied. Two
      new species are described: A. lechrilophodes sp. nov. and A. xuthus sp. nov., and
      a key to the identification of Old World Ademon is provided. 

PMID- 24870325
TI  - First record of Hiroshia Laszlo, Ronkay & Ronkay from China, with description of
      a new species (Lepidoptera: Thyatiridae).
AB  - The monotypical genus Hiroshia and the type species, H. albinigra Laszlo, Ronkay
      & Ronkay, 2001 from North Vietnam are recorded for the first time from China,
      with description of a new species, H. nanlingana sp. n. Adults and genitalia are
      illustrated and a distribution map of Hiroshia is provided. 

PMID- 24870327
TI  - 'Googleology' revisited: an additional tool for preventing zoological homonymy.

PMID- 24870328
TI  - Reef sponges of the genus Agelas (Porifera: Demospongiae) from the Greater
      Caribbean.
AB  - The genus Agelas comprises a group of tropical and subtropical reef sponges that
      contains large, long-lived, often brightly colored and conspicuous species,
      distributed throughout the tropica l western Atlantic, temperate northern
      Atlantic (Mediterranean Sea), and western and central Indo-Pacific Realms. Among
      tropical sponge genera, Agelas is one with similar species richness in the
      Greater Caribbean in comparison to the Indo Pacific. The presence of
      verticillated acanthostyle spicules and a fibroreticulate skeleton of spongin
      fibres cored and/or echinated by spicules characterize this group. Taxonomic
      identification relies on a combination of characters, where external morphology
      and color play a key role, owing to the paucity of microscopical characters.
      Thus, there is still a great deal of taxonomic confusion, even for the more
      common species. We carried out a detailed revision of Agelas species throughout
      the Greater Caribbean area using classic taxonomic tools. Samples and
      observations covered Colombia, Belize, Jamaica, the Bahamas, Barbados, Curacao
      and Venezuela, and included type material from major museum collections.
      According to our results, the genus Agelas in the Caribbean has at least thirteen
      valid species, viz. Agelas sceptrum (Lamarck, 1815); A. dispar Duchassaing &
      Michelotti, 1864;  A. dilatata Duchassaing & Michelotti, 1864; A. clathrodes
      (Schmidt, 1870);  A. cervicornis (Schmidt, 1870); A. conifera (Schmidt, 1870); A.
      schmidti Wilson, 1902;   A. tubulata Lehnert & van Soest, 1996; A. wiedenmayeri
      Alcolado, 1984;  A. citrina Gotera & Alcolado, 1987; A. sventres Lehnert & van
      Soest, 1996; A. repens Lehnert & van Soest, 1998; and A. cerebrum Assmann et al.,
      2001. We found that variation of microscopic characteristics like skeleton
      arrangement, number of verticills and their spines, and spicule length and width,
      can be used as taxonomic tools, but only in a thorough comparison with other
      species in the same sub-regional context. Thus, a certain degree of familiarity
      with the genus' regional variation is often required. The richness and
      distribution of these species in the Caribbean area show north/south differences
      and other ecological patterns are evident.  

PMID- 24870329
TI  - Review of the genus Cratyna Winnertz (Diptera: Sciaridae) in Korea, including the
      description of a new species.
AB  - The genus Cratyna Winnertz, 1867 (Diptera: Sciaridae) is studied in the Korean
      peninsula. Cratyna (s. str.) suwonensis Shin, Menzel & Lee sp. nov. is described
      as new to science. Additionally, three species are redescribed and illustrated as
      new to Korea: C. (s. str.) ambigua (Lengersdorf, 1934), C. (s. str.) nigerrima
      (Mohrig & Krivosheina, 1979), and C. (Peyerimhoffia) vagabunda (Winnertz, 1867).
      A key to the Korean species is given.  

PMID- 24870330
TI  - Diversity and systematics of Haminoeidae gastropods (Heterobranchia:
      Cephalaspidea) in the tropical West Pacific Ocean: new data on the genera
      Aliculastrum, Atys, Diniatys and Liloa.
AB  - Four genera of Haminoeidae gastropods inhabiting the tropical West Pacific
      (Aliculastrum, Atys, Diniatys, and Liloa) were studied based on the combined
      analyses of live animals, external morphology, anatomy and shells aided by
      scanning electron microscopy and molecular sequencing. Eleven species are
      described including two new to Science, namely Atys pittmani sp. nov. and Atys
      ukulele sp. nov.. The putative synapomorphies of the genera Aliculastrum,
      Diniatys, and Liloa are discussed. High levels of morpho-anatomical variability
      were found among representatives of the genus Atys, which hampered the
      recognition of synapomorphies.  

PMID- 24870331
TI  - The hawkmoth fauna of Pakistan (Lepidoptera: Sphingidae).
AB  - This study represents the first complete modern account of the Sphingidae of
      Pakistan and takes the form of an annotated checklist, based on several national
      collections and those of a number of individuals. Of the 60 species and
      subspecies found, 14 are new records to the fauna of Pakistan, namely Agnosia
      orneus, Langia zenzeroides subsp. zenzeroides, Polyptychus trilineatus subsp.
      trilineatus, Dolbina inexacta, Ambulyx sericeipennis subsp. sericeipennis,
      Thamnoecha uniformis, Macroglossum belis, Macroglossum stellatarum, Cechetra
      scotti, Hippotion boerhaviae, Hyles euphorbiae subsp. euphorbiae, Rhagastis
      olivacea, Rethera brandti subsp. euteles and Theretra latreillii subsp. lucasii.
      Anambulyx elwesi subsp. kitchingi and Clanis deucalion subsp. thomaswitti are not
      recognised as valid subspecies and are synonymized with their respective
      nominotypical subspecies. An additional list is given of 30 taxa which may yet be
      found in Pakistan as they are present in neighbouring countries close to the
      border. Of the species/subspecies found, 24 are part of the Palaearctic fauna, 27
      are part of the Oriental fauna and nine are Palaeo-Oriental/Palaeotropical. This
      reconfirms the transitional biogeographical position of the Pakistan fauna. 

PMID- 24870332
TI  - A revision of Hoplasoma acuminatum and H. thailandicum species groups, and re
      definition of H. unicolor species group(Coleoptera: Chrysomelidae: Galerucinae).
AB  - Two species groups within the genus Hoplasoma Jacoby, 1884 are defined and
      revised. The Hoplasoma acuminatum species group is established for H. acuminatum
      Medvedev, 2000 and H. sumatranum Medvedev, 2000, and the Hoplasoma thailandicum
      species group for H. thailandicum Kimoto, 1989; H. vithala sp. nov. (Vietnam,
      Laos, Thailand) and H. andrewesi sp. nov. (Myanmar). Hoplasoma unicolor species
      group is re-defined. The male of H. acuminatum, to date unknown, is described.
      Colour photo of habitus and both male and female genitalia are provided for all
      the species revised. The checklist of all species currently classified in
      Hoplasoma is provided. 

PMID- 24870333
TI  - Antillipeltis, a new genus of Antillean Trogossitidae (Coleoptera: Cleroidea)
      with a key to the Cleroidea.
AB  - Antillipeltis gen. nov. is described based on the following six new extant
      species and two new fossil species from Hispaniola and Puerto Rico: A. alleni sp.
      nov. (Dominican Republic, Miocene), A. darlingtoni sp. nov. (Haiti), A. iviei sp.
      nov. (Dominican Republic, Miocene), A. maculata sp. nov. (Dominican Republic), A.
      minuta sp. nov. (Dominican Republic), A. nitida sp. nov. (Puerto Rico), A.
      portoricensis sp. nov. (Puerto Rico), and A. pubescens sp. nov. (Dominican
      Republic). The genus is placed in Cleroidea, as currently delimited, based on the
      presence of a distinctive type of aedeagus occurring primarily in this
      superfamily, plus a combination of features excluding it from other cucujiform
      superfamilies. Within Cleroidea, the genus is tenatively placed in the family
      Trogossitidae and subfamily Lophocaterinae, but it differs from all other
      Trogossitidae in the presence of ventral membranous lobes with adhesive setae on
      tarsomeres 1-4 and in a combination of 9-segmented antennae, weak 3-segmented
      antennal club consisting of slightly elongate antenomeres, lack of postcoxal
      processes on the pronotal hypomera, and unique leg modifications. A key is
      provided for major groups of Cleroidea and all described genera of Peltinae and
      Lophocaterinae, with the exception of Rentoniini, based in part on the literature
      and in part on dissections of adult males. Antillipeltis is one of three endemic
      West Indian genera of Coleoptera that is both extant and known from Dominican
      amber. 

PMID- 24870334
TI  - Pelagia benovici sp. nov. (Cnidaria, Scyphozoa): a new jellyfish in the
      Mediterranean Sea.
AB  - A bloom of an unknown semaestome jellyfish species was recorded in the North
      Adriatic Sea from September 2013 to early 2014. Morphological analysis of several
      specimens showed distinct differences from other known semaestome species in the
      Mediterranean Sea and unquestionably identified them as belonging to a new
      pelagiid species within genus Pelagia. The new species is morphologically
      distinct from P. noctiluca, currently the only recognized valid species in the
      genus, and from other doubtful Pelagia species recorded from other areas of the
      world. Molecular analyses of mitochondrial cytochrome c oxidase subunit I (COI)
      and nuclear 28S ribosomal DNA genes corroborate its specific distinction from P.
      noctiluca and other pelagiid taxa, supporting the monophyly of Pelagiidae. Thus,
      we describe Pelagia benovici sp. nov. Piraino, Aglieri, Scorrano & Boero. 

PMID- 24870335
TI  - Two new species of Hygronemobius Hebard, 1913 (Orthoptera, Grylloidea,
      Nemobiinae) from Brazilian Amazon.
AB  - Two new Neotropical species of Hygronemobius Hebard were described from Brazilian
      Amazon: Hygronemobius duckensis sp. nov. and Hygronemobius dialeucus sp. nov.
      Photographs of habitus, morphological characteristics and male genitalia were
      provided. Calling songs and spectrograms of the new species were characterized. 

PMID- 24870336
TI  - Obesoconnus gen. n., a new bizarre Neotropical genus of Cyrtoscydmini
      (Coleoptera: Staphylinidae: Scydmaeninae).
AB  - A new Neotropical genus of Cyrtoscydmini, Obesoconnus gen. n., is described to
      accommodate two new species: O. guyanensis sp. n. (the type species of
      Obesoconnus) from French Guyana and O. mexicanus sp. n. from Mexico. The
      morphology of the new taxon is described and illustrated in detail, and its
      possible affinities to other Cyrtoscydmini are discussed. Despite external
      dissimilarities, the aedeagus of Obesoconnus highly resembles copulatory organs
      of Alloraphes and Parastenichnaphes; all these genera share the basal pumping
      apparatus and apically located ostium with asymmetrical apical projections. 

PMID- 24870337
TI  - Astyanax douradilho, a new characid fish from the rio Tramandai system, southern
      Brazil (Characiformes: Characidae).
AB  - Astyanax douradilho, new species, is described from the rio Tramandai system,
      coastal drainage of Rio Grande do Sul State, Brazil. The new species is
      distinguished from its congeners by possessing 37-39 perforated scales along the
      lateral line, 3-5 maxillary tricuspid teeth, 22-24 branched anal-fin rays,
      absence of a conspicuous dark stripe from humeral region to caudal peduncle, two
      vertically elongated humeral spots, head length (26.0-29.9% of standard length),
      upper jaw length (43.8-50.6% of head length), and snout length (23.0-28.6% of
      HL). 

PMID- 24870338
TI  - A new species of Shaanxispira (Bovidae, Artiodactyla) from the upper Miocene of
      China.
AB  - A new species of the bovid Shaanxispira, from the upper Miocene deposits of the
      Linxia Basin, Gansu Province, China, is described here. Shaanxispira is endemic
      to Northern China and was previously known only from the Lantian area, Shaanxi
      Province, by two species, S. chowi and S. baheensis. The new species, S.
      linxiaensis nov. sp., is of early Bahean in age, slightly older than the species
      from the Lantian area. The horn-cores of the new species are more derived, with
      large wing-shaped antero-medial keels, suggesting the occurrence of a different
      lineage of Shaanxispira in the Linxia Basin. Although Shaanxispira has
      homonymously twisted horn-cores, it is not closely related to other late Miocene
      bovids with homonymously twisted horn-cores, like Oioceros and Samotragus. Its
      phylogenetic status is still in debate, but might be more closely related to the
      late Miocene "ovibovines."  

PMID- 24870339
TI  - A new species of land flatworm (Platyhelminthes: Continenticola) from areas of
      Araucaria Forest in southern Brazil.
AB  - The genus Cratera Carbayo et al. was proposed to encompass five species of
      Geoplaninae from southeastern Brazil that were mainly recorded in the state of
      Sao Paulo. Here we describe a new species of the genus, C. steffeni sp. nov.,
      that occurs in areas of Araucaria Forest in southern Brazil, which augments the
      known distribution of Cratera. The new species is distinguished from others of
      the genus by its characteristic colour pattern and a combination of internal
      morphological characters. 

PMID- 24870340
TI  - A review of the genus Syrastrenopsis Grunberg, 1914 (Lepidoptera, Lasiocampidae).
AB  - The genus Syrastrenopsis Grunberg, 1914 is revised and two new species, S. panga
      Zolotuhin & Saldaitis, sp. nov. and S. hun Zolotuhin & Saldaitis, sp. nov. are
      described from North Sichuan and Shaanxi Provinces of China, respectively. All
      species of the genus are illustrated including the male of S. imperiatus
      Zolotuhin, 2001 which is described for the first time.  

PMID- 24870341
TI  - Three new Afrotropical species of Tersilochinae (Hymenoptera: Ichneumonidae) from
      the Kibale National Park, Uganda.
AB  - Seven species of Tersilochinae (Hymenoptera: Ichneumonidae) have been found from
      Uganda in Equatorial Africa: Allophrys budongoana Khalaim, Diaparsis
      interstitialis Khalaim, D. kanyawara sp. nov., D. mostovskii Khalaim, D. sinuator
      sp. nov., D. umbrosa sp. nov. and Tersilochus moestus Holmgren. Two species of
      Diaparsis, described in this paper, possess a white banded flagellum, and a key
      to the group of four Afrotropical species having a white-banded flagellum is
      provided. Tersilochus moestus Holmgren, previously known only from a single
      female from South Africa, is recorded from the Kibale National Park, Uganda.
      Antennae and ovipositor of this species, broken in the type specimen, are
      described for the first time.  

PMID- 24870342
TI  - Anacampsis rhoifructella (Clemens): clarification of its identity and larval
      biology, and differentiation from a similar species, Anacampsis consonella
      (Zeller), revised status (Lepidoptera: Gelechiidae).
AB  - Anacampsis rhoifructella (Clemens) (Lepidoptera: Gelechiidae) was described from
      individuals reared from larvae collected in fruit racemes of staghorn sumac, Rhus
      typhina (Anacardiaceae). Rearing efforts in central Illinois, however, have
      established that A. rhoifructella actually feeds on leaves of Viburnum
      prunifolium (Caprifoliaceae). Furthermore, a second Anacampsis species also feeds
      on leaves of V. prunifolium. The second species is very similar to A.
      rhoifructella in external appearance of the adult and in larval feeding mode but
      is readily differentiated on basis of larval appearance, phenology, and genital
      morphology of both genders. Examination of type specimens of Gelechia consonella
      Zeller, G. quadrimaculella Chambers, and G. ochreocostella Chambers, all of which
      were previously designated as junior synonyms of A. rhoifructella, revealed that
      the valid name of the second species is Anacampsis consonella (Zeller, 1873),
      revised status; G. ochreocostella and G. quadrimaculella are assigned as junior
      synonyms of A. consonella. We provide descriptions and illustrations of
      characters that reliably differentiate A. rhoifructella from A. consonella. We
      conclude that Clemens' record of A. rhoifructella feeding on fruits of sumac is
      erroneous, and we offer an explanation of how the error probably occurred. 

PMID- 24870343
TI  - Three new species of Tuberepyris Lanes et Azevedo (Hymenoptera, Bethylidae), with
      amended diagnosis of the genus.
AB  - Three new species of the Afrotropical Tuberepyris are described and illustrated,
      T. nihilus Azevedo et Mugrabi, sp. nov. (Madagascar), T. codex Azevedo et
      Mugrabi, sp. nov. (South Africa), and T. hamus Azevedo et Mugrabi, sp. nov.
      (Central African Republic). The male of Tuberepyris is described for the first
      time. T. basibrevis Lanes et Azevedo from Tanzania is evaluated and the genus is
      redefined. A key to species of Tuberepyris is provided. 

PMID- 24870344
TI  - Two new species of Didicrum Enderlein (Diptera, Psychodidae, Psychodinae) from
      Argentinean Patagonia.
AB  - Two new species of Didicrum from Argentina are described and illustrated:
      Didicrum naimae and Didicrum letitiae, based on male and female specimens.
      Specimens were collected with Malaise traps located in Nahuel Huapi National
      Park, Patagonian region. Including the two new species of Didicrum, twelve are
      described from South America.  

PMID- 24870345
TI  - A new subgenus and species of Topomyia (Diptera: Culicidae: Sabethini) based on a
      remarkable male mosquito from Sabah, Malaysia.
AB  - Miyagiella Harbach, subgen. nov., is introduced as a new subgenus of Topomyia
      Leicester for a remarkable male mosquito, Topomyia discors Harbach, sp. nov.,
      from Sabah, Malaysia. A diagnosis of the subgenus is provided that features
      unique anatomical characters of the genitalia of the holotype male. Miyagiella is
      very distinct from the two previously recognised subgenera of Topomyia, but is
      perhaps more closely related to the nominotypical subgenus than to subgenus
      Suaymyia Thurman. Salient differences that distinguish the three subgenera are
      contrasted; the holotype male of To. discors is described and its unique
      genitalia are illustrated. 

PMID- 24870346
TI  - A new genus of Podonominae (Diptera: Chironomidae) in Late Eocene Rovno amber
      from Ukraine.
AB  - The genus Palaeoboreochlus Baranov et Andersen, n. gen. is erected based on P.
      inornatus Baranov et Andersen, n. sp. described from a male found in Late Eocene
      Rovno amber. The new genus groups with Boreochlus Edwards in the tribe
      "Boreochlini". 

PMID- 24870347
TI  - Concavocorona, a new genus of the leafhopper subfamily Evacanthinae (Hemiptera:
      Cicadellidae), with description of a new species.
AB  - Concavocorona, gen. n., is described and illustrated based on a new species C.
      supercilia sp. n. from Thailand. In addition, C. abbreviata (Jacobi, 1944), n.
      comb. from China is transferred to this genus from Cunedda Distant, and its male
      genitalia is described for the first time. 

PMID- 24870348
TI  - Mesodiplatys venado sp. nov. (Dermaptera: Diplatyidae), probable evidence of
      contact between Neotropical and Malagasy faunas.
AB  - A new earwig of the Malagasy genus Mesodiplatys stat. nov., M. venado sp. nov.
      (Dermaptera: Diplatyidae) is described from Peru (Departament Junin, Satipo
      Province). The diagnosis and composition of the genus Mesodiplatys stat. nov. are
      discussed. A detailed morphological description of the new species is given. The
      possible biogeographical significance of the find as evidence of link between
      South American and Malagasy fauna is briefly considered. 

PMID- 24870351
TI  - Superparamagnetic iron oxide nanoparticles for delivery of therapeutic agents:
      opportunities and challenges.
AB  - INTRODUCTION: Bearing in mind that many promising drug candidates have the
      problem of reaching their target site, the concept of advanced drug delivery can
      play a significant complementary role in shaping modern medicine. Among other
      nanoscale drug carriers, superparamagnetic iron oxide nanoparticles (SPIONs) have
      shown great potential in nanomedicine. The intrinsic properties of SPIONs, such
      as inherent magnetism, broad safety margin and the availability of methods for
      fabrication and surface engineering, pave the way for diverse biomedical
      applications. SPIONs can achieve the highest drug targeting efficiency among
      carriers, since an external magnetic field locally applied to the target organ
      enhances the accumulation of magnetic nanoparticles in the drug site of action.
      Moreover, theranostic multifunctional SPIONs make simultaneous delivery and
      imaging possible. In spite of these favorable qualities, there are some
      toxicological concerns, such as oxidative stress, unpredictable cellular
      responses and induction of signaling pathways, alteration in gene expression
      profiles and potential disturbance in iron homeostasis, that need to be carefully
      considered. Besides, the protein corona at the surface of the SPIONs may induce
      few shortcomings such as reduction of SPIONs targeting efficacy. AREAS COVERED:
      In this review, we will present recent developments of SPIONs as theranostic
      agents. The article will further address some barriers on drug delivery using
      SPIONs. EXPERT OPINION: One of the major success determinants in targeted in vivo
      drug delivery using SPIONs is the adequacy of magnetic gradient. This can be
      partially achieved by using superconducting magnets, local implantation of
      magnets and application of magnetic stents. Other issues that must be considered
      include the pharmacokinetics and in vivo fate of SPIONs, their biodegradability,
      biocompatibility, potential side effects and the crucial impact of protein corona
      on either drug release profile or mistargeting. Surface modification of SPIONs
      can open up the possibility of drug delivery to intracellular organelles, drug
      delivery across the blood-brain barrier, modifying metabolic diseases and a
      variety of other multimodal and/or theranostic applications.

PMID- 24870352
TI  - Fully automated artificial pancreas finally within reach.

PMID- 24870350
TI  - Assessing patients' and caregivers' perspectives on stability of factor VIII
      products for haemophilia A: a web-based study in the United States and Canada.
AB  - Haemophilia A is a rare inherited bleeding disorder characterized by an inability
      of the blood to clot normally. Patients can experience spontaneous or trauma
      induced joint and soft tissue bleeding and must keep coagulation factor VIII
      (FVIII) accessible at all times; thus, FVIII product storage and stability are
      critical. Our primary objective was to assess haemophilia A patients' and
      caregivers' experiences and preferences with FVIII product storage and stability.
      A secondary objective was to evaluate the use of the social media site Facebook
      in recruitment. In this cross-sectional study, 145 English-speaking adult
      patients and caregivers of children with haemophilia A were recruited through two
      state-based haemophilia organizations in the United States (US) and one national
      organization in Canada for a web-based survey assessing demographics and FVIII
      product ordering, usage, and storage practices. Of the 101 individuals who
      completed the survey, 60% resided in Canada; 57% were recruited through Facebook.
      Caregivers and patients responded similarly to questions about ordering practices
      and product usage, with some distinction between groups in storage practices. Two
      thirds of participants noted challenges with storing FVIII products, especially
      storage away from home. More than half preferred storing FVIII products at room
      temperature vs. in the refrigerator for long periods of time. FVIII product
      accessibility, usage and storage affect disease management. Results support the
      need for more convenient and accessible FVIII products for patients in daily life
      and while travelling. In addition, the use of social media has potential value in
      recruiting this population. 

PMID- 24870354
TI  - Sugar sweetened drinks should carry obesity warnings.

PMID- 24870355
TI  - Research governance as a facilitator for ethical and timely research? Learning
      from the experience of a large government-funded multisite research project.
AB  - OBJECTIVE: The processes of research ethics and research governance are core to
      the conduct of research in health. Each aims to facilitate research that is both
      ethical and practical in order to produce new knowledge about the health system
      and improve the lives of those who use it. However, our experience has
      demonstrated that the process of obtaining ethical approval for a low-risk and
      low-resource research project was severely confounded by the multiple layers of
      research governance in operation at hospitals in Queensland (Qld) and New South
      Wales (NSW). METHODS: We analysed our own experience of gaining research
      governance approval with the aim of improving governance processes for
      multicentre research projects. Our project aimed to interview and survey one
      person at each of 57 hospitals in NSW and 18 in Qld. We recorded and compared the
      steps, documents and time-frame related to research governance approval at each
      of these research sites. RESULTS: We found that the progress of our project was
      significantly impeded by the multiple steps related to research governance
      processes in hospitals. Research governance approval took an average of 160 days
      in NSW and 316 in Qld. There was inconsistency between hospitals regarding
      documentation and significant duplication of documentation already approved
      through ethical review processes. The necessity for separate research contracts
      for all Qld research sites also added to research delays. CONCLUSION: Based on
      our experiences we make recommendations about changes to research governance
      including clarification of responsibility, reform of areas of duplication and
      inconsistency, time limitations for approval and, in Qld, reform of financial and
      legal oversight.

PMID- 24870353
TI  - The potential biomarker panels for identification of Major Depressive Disorder
      (MDD) patients with and without early life stress (ELS) by metabonomic analysis.
AB  - OBJECTIVE: The lack of the disease biomarker to support objective laboratory
      tests still constitutes a bottleneck in the clinical diagnosis and evaluation of
      major depressive disorder (MDD) and its subtypes. We used metabonomic techniques
      to screen the diagnostic biomarker panels from the plasma of MDD patients with
      and without early life stress (ELS) experience. METHODS: Plasma samples were
      collected from 25 healthy adults and 46 patients with MDD, including 23 patients
      with ELS and 23 patients without ELS. Furthermore, gas chromatography/mass
      spectrometry (GC/MS) coupled with multivariate statistical analysis was used to
      identify the differences in global plasma metabolites among the 3 groups.
      RESULTS: The distinctive metabolic profiles exist either between healthy subjects
      and MDD patients or between the MDD patients with ELS experience (ELS/MDD
      patients) and the MDD patients without it (non-ELS/MDD patients), and some
      diagnostic panels of feature metabolites' combination have higher predictive
      potential than the diagnostic panels of differential metabolites. CONCLUSIONS:
      These findings in this study have high potential of being used as novel
      laboratory diagnostic tool for MDD patients and it with ELS or not in clinical
      application.

PMID- 24870356
TI  - Using a nursing theory or a model in nursing PhD dissertations: a qualitative
      study from Turkey.
AB  - PURPOSE: The aim of this study was to reveal experiences of nursing students and
      their advisors using theories and models in their PhD dissertations. METHODS: The
      study adopted a descriptive qualitative approach. This study was performed with
      10 PhD candidates and their five advisors from nursing faculty. RESULTS: The
      results of the study were categorized into four. These are reasons for using a
      theory/model in a PhD dissertation, reasons for preferring a given model, causes
      of difficulties in using models in PhD dissertations, and facilitating factors of
      using theories and models in PhD of dissertations. CONCLUSIONS: It was also
      reported to contribute to the methodology of research and professional
      development of the students and advisors.

PMID- 24870358
TI  - Pentacenobis(thiadiazole)dione, an n-type semiconductor for field-effect
      transistors.
AB  - A new heteroacenequinone, pentaceno[2,3-c:9,10-c']bis([1,2,5]thiadiazole)-6,13
      dione (PBTDQ), with two peripheral thiadiazole rings was synthesized, and its
      solid-state properties were characterized. The fused planar structure with a low
      lying LUMO and low reorganization energy facilitates electron transport,
      affording MUe values of up to 0.11 cm(2) V(-1) s(-1) in field-effect transistor
      devices. 

PMID- 24870359
TI  - Crown ether adducts of light alkali metal triphenylsilyls: synthesis, structure
      and hydrosilylation catalysis.
AB  - Alkali metal triphenylsilyls [Li(12-crown-4)SiPh3].(thf)0.5 (2), [Na(15-crown
      5)SiPh3].(thf)0.5 (3) and [K(18-crown-6)SiPh3(thf)] (4) were synthesized using
      1,1,1-trimethyl-2,2,2-triphenyldisilane (Ph3SiSiMe3) and isolated in high yields.
      Solid state structures were determined by single crystal X-ray diffraction. These
      alkali metal silyls catalyzed the regioselective hydrosilylation of 1,1
      diphenylethylene to give the anti-Markovnikov product. The presence of crown
      ethers enhanced the reactivity of the metal silyls in hydrosilylation catalysis.

PMID- 24870357
TI  - Gene expression profiles of human dendritic cells interacting with Aspergillus
      fumigatus in a bilayer model of the alveolar epithelium/endothelium interface.
AB  - The initial stages of the interaction between the host and Aspergillus fumigatus
      at the alveolar surface of the human lung are critical in the establishment of
      aspergillosis. Using an in vitro bilayer model of the alveolus, including both
      the epithelium (human lung adenocarcinoma epithelial cell line, A549) and
      endothelium (human pulmonary artery epithelial cells, HPAEC) on transwell
      membranes, it was possible to closely replicate the in vivo conditions. Two
      distinct sub-groups of dendritic cells (DC), monocyte-derived DC (moDC) and
      myeloid DC (mDC), were included in the model to examine immune responses to
      fungal infection at the alveolar surface. RNA in high quantity and quality was
      extracted from the cell layers on the transwell membrane to allow gene expression
      analysis using tailored custom-made microarrays, containing probes for 117 immune
      relevant genes. This microarray data indicated minimal induction of immune gene
      expression in A549 alveolar epithelial cells in response to germ tubes of A.
      fumigatus. In contrast, the addition of DC to the system greatly increased the
      number of differentially expressed immune genes. moDC exhibited increased
      expression of genes including CLEC7A, CD209 and CCL18 in the absence of A.
      fumigatus compared to mDC. In the presence of A. fumigatus, both DC subgroups
      exhibited up-regulation of genes identified in previous studies as being
      associated with the exposure of DC to A. fumigatus and exhibiting chemotactic
      properties for neutrophils, including CXCL2, CXCL5, CCL20, and IL1B. This model
      closely approximated the human alveolus allowing for an analysis of the host
      pathogen interface that complements existing animal models of IA. 

PMID- 24870361
TI  - Genotoxicity in earthworm after combined treatment of ionising radiation and
      mercury.
AB  - This study was performed to investigate the acute genotoxic effects of mercury
      and radiation on earthworms (Eisenia fetida). The levels of DNA damage and the
      repair kinetics in the coelomocytes of E. fetida treated with mercuric chloride
      (HgCl2) and ionising radiation (gamma rays) were analysed by means of the comet
      assay. For detection of DNA damage and repair, E. fetida was exposed to HgCl2 (0
      160 mg kg(-1)) and irradiated with gamma rays (0-50 Gy) in vivo. The increase in
      DNA damage depended on the concentration of mercury or dose of radiation. The
      results showed that the more the oxidative stress induced by mercury and
      radiation the longer the repair time that was required. When a combination of
      HgCl2 and gamma rays was applied, the cell damage was much higher than those
      treated with HgCl2 or radiation alone, which indicated that the genotoxic effects
      were increased after the combined treatment of mercury and radiation.

PMID- 24870360
TI  - Current situation and associated factors of withdrawing or withholding life
      support to patients in an intensive care unit of cancer center in China.
AB  - OBJECTIVES: To investigate the current situation and analyze the associated
      factors of withdrawing or withholding life support in the intensive care unit
      (ICU) of our cancer center. METHODS: Three hundred and twenty-two cancer patients
      in critical status were admitted to our ICU in 2010 and 2011. They were included
      in the study and were classified into two groups: withdrawing or withholding life
      support (WWLS), and full life support (FLS). Demographic information and clinical
      data were collected and compared between the two groups. Factors associated with
      withdrawing or withholding life support were analyzed with univariate and
      multivariate logistic regression analysis. RESULTS: Eighty-two of the 322 cases
      (25.5% of all) made the decisions to withdraw or withhold life support. Emergency
      or critical condition at hospital admission, higher scores of Acute Physiology
      and Chronic Health Evaluation II (APACHE II) in 12 hours after ICU admission,
      financial difficulties and humanistic care requirements are important factors
      associated with withdrawing or withholding life support. CONCLUSIONS: Withdrawing
      or withholding life support is not uncommon in critically ill cancer patients in
      China. Characteristics and associated factors of the decision-making are related
      to the current medical system, medical resources and traditional culture of the
      country.

PMID- 24870362
TI  - Dose and dose-rate response of lymphocyte chromosome aberrations in mice
      chronically irradiated within a low-dose-rate range after age adjustment.
AB  - The incidences of chromosome aberrations were analysed in splenic lymphocytes
      from mice that were continuously exposed to (137)Cs gamma rays within the low
      dose-rate (LDR) range to evaluate the dose-response and dose-rate effects.
      Chromosome aberrations were detected by fluorescence in situ hybridisation
      method, and these were found to increase in frequency up to 8000 mGy at 20 mGy
      for 22 h d(-1) and to 700 mGy at 1 mGy for 22 h d(-1). Translocations increased
      in a linear quadratic manner with age in non-exposed mice. The dose-response
      relationship for the frequency of translocations at each dose rate (20 and 1 mGy
      for 22 h d(-1)) was obtained using age-adjusted multiple linear regression
      analysis. Values of the linear term, shown as the slope, decreased as the dose
      rate was reduced from 20 to 1 mGy for 22 h d(-1), indicating a positive dose-rate
      effect in the LDR range. These results will be useful for estimating the risk of
      LDR radiation exposure and radiation protection. 

PMID- 24870363
TI  - Uptake, translocation, and transformation of quantum dots with cationic versus
      anionic coatings by Populus deltoides * nigra cuttings.
AB  - Manipulation of the organic coatings of nanoparticles such as quantum dots (QDs)
      to enhance specific applications may also affect their interaction and uptake by
      different organisms. In this study, poplar trees (Populus deltoides * nigra) were
      exposed hydroponically to 50-nM CdSe/CdZnS QDs coated with cationic
      polyethylenimine (PEI) (35.3 +/- 6.6 nm) or poly(ethylene glycol) of anionic
      poly(acrylic acid) (PAA-EG) (19.5 +/- 7.2 nm) to discern how coating charge
      affects nanoparticle uptake, translocation, and transformation within woody
      plants. Uptake of cationic PEI-QDs was 10 times faster despite their larger
      hydrodynamic size and higher extent of aggregation (17 times larger than PAA-EG
      QDs after 11-day incubation in the hydroponic medium), possibly due to
      electrostatic attraction to the negatively charged root cell wall. QDs cores
      aggregated upon root uptake, and their translocation to poplar shoots (negligible
      for PAA-EG-QDs and 0.7 ng Cd/mg stem for PEI-QDs) was likely limited by the
      endodermis. After 2-day exposure, PEI and PAA-EG coatings were likely degraded
      from the internalized QDs inside the plant, leading to the aggregation of the
      metallic cores and a "red-shift" of fluorescence. The fluorescence of PEI-QD
      aggregates was stable inside the roots through the 11-day exposure period. In
      contrast, the PAA-EG-QD aggregates lost fluorescence inside the plant after 11
      days probably due to destabilization of the coating, even though these QDs were
      stable in the hydroponic solution. Overall, these results highlight the
      importance of coating properties in the rate and extent to which nanoparticles
      are assimilated by plants and potentially introduced into food webs. 

PMID- 24870365
TI  - Investigation of the component processes involved in verbal declarative memory
      function in bipolar disorder: utility of the Hopkins Verbal Learning Test
      Revised.
AB  - Evidence suggests that standard learning and recall indexes are sensitive markers
      of verbal declarative memory ability in bipolar disorder (BD), but no study has
      examined performance across the full range of component process measures on the
      Hopkins Verbal Learning Test (HVLT-R) in a BD cohort. As the HVLT-R is part of a
      widely used battery of cognitive functioning backed by the U.S. Federal Drug
      Administration as the accepted battery for use in pro-cognitive trials assessing
      cognitive-enhancing drugs in the related disorder schizophrenia, estimating the
      utility of its measures in BD is important. Forty-nine BD patients and 51 healthy
      controls completed the HVLT-R, which was scored for 13 variables of interest,
      across 4 indices: recall and learning, recognition, strategic organization, and
      errors. BD patients had greater difficulty in learning the HVLT-R word list
      compared to controls. They also demonstrated impairment in delayed
      recall/recognition. There were no differences between the groups in terms of
      their slope of learning, retrieval index, retention percentage, semantic or
      serial clustering, errors, or level of retrieval. This pattern was consistent
      across symptomatic and euthymic patients. The HVLT-R has some utility in
      characterizing the component processes involved in memory function in BD, such
      that memory impairments appear to be attributable to deficient encoding processes
      during the acquisition phase of learning. In the case of planning pro-cognitive
      clinical trials, the encoding deficits in BD observed here may be sensitive
      enough to potentially respond to medications designed to enhance the verbal
      memory performance.

PMID- 24870364
TI  - A fragment-based method to discover irreversible covalent inhibitors of cysteine
      proteases.
AB  - A novel fragment-based drug discovery approach is reported which irreversibly
      tethers drug-like fragments to catalytic cysteines. We attached an electrophile
      to 100 fragments without significant alterations in the reactivity of the
      electrophile. A mass spectrometry assay discovered three nonpeptidic inhibitors
      of the cysteine protease papain. The identified compounds display the
      characteristics of irreversible inhibitors. The irreversible tethering system
      also displays specificity: the three identified papain inhibitors did not
      covalently react with UbcH7, USP08, or GST-tagged human rhinovirus 3C protease. 

PMID- 24870366
TI  - Unravelling spatiotemporal tree-ring signals in Mediterranean oaks: a variance
      covariance modelling approach of carbon and oxygen isotope ratios.
AB  - Identifying how physiological responses are structured across environmental
      gradients is critical to understanding in what manner ecological factors
      determine tree performance. Here, we investigated the spatiotemporal patterns of
      signal strength of carbon isotope discrimination (Delta(13)C) and oxygen isotope
      composition (delta(18)O) for three deciduous oaks (Quercus faginea (Lam.), Q.
      humilis Mill. and Q. petraea (Matt.) Liebl.) and one evergreen oak (Q. ilex L.)
      co-occurring in Mediterranean forests along an aridity gradient. We hypothesized
      that contrasting strategies in response to drought would lead to differential
      climate sensitivities between functional groups. Such differential sensitivities
      could result in a contrasting imprint on stable isotopes, depending on whether
      the spatial or temporal organization of tree-ring signals was analysed. To test
      these hypotheses, we proposed a mixed modelling framework to group isotopic
      records into potentially homogeneous subsets according to taxonomic or
      geographical criteria. To this end, carbon and oxygen isotopes were modelled
      through different variance-covariance structures for the variability among years
      (at the temporal level) or sites (at the spatial level). Signal-strength
      parameters were estimated from the outcome of selected models. We found striking
      differences between deciduous and evergreen oaks in the organization of their
      temporal and spatial signals. Therefore, the relationships with climate were
      examined independently for each functional group. While Q. ilex exhibited a large
      spatial dependence of isotopic signals on the temperature regime, deciduous oaks
      showed a greater dependence on precipitation, confirming their higher
      susceptibility to drought. Such contrasting responses to drought among oak types
      were also observed at the temporal level (interannual variability), with stronger
      associations with growing-season water availability in deciduous oaks. Thus, our
      results indicate that Mediterranean deciduous and evergreen oaks constitute two
      clearly differentiated functional groups in terms of their carbon and water
      economies, despite co-existing in a wide range of environments. In contrast,
      deciduous oaks form a rather homogeneous group in terms of climate sensitivity. 

PMID- 24870367
TI  - Innovation toward better living.

PMID- 24870368
TI  - A case of infantile neuroaxonal dystrophy of neonatal onset.
AB  - Infantile neuroaxonal dystrophy is a rare neurodegenerative disorder, with onset
      in the first or second year of life. Mutations in the PLA2G6 gene encoding iPLA2
      VI, a calcium-independent phospholipase, have been identified in these children.
      In classic infantile neuroaxonal dystrophy-affected children, psychomotor
      regression is the most frequent presentation, usually with ataxia and optic
      atrophy, followed by the development of tetraparesis. We report a child carrying
      a homozygous mutation in the PLA2G6 gene with neonatal onset of disease and
      somewhat different clinical phenotype such as severe congenital hypotonia, marked
      weakness, and bulbar signs suggesting that infantile neuroaxonal dystrophy can
      start at birth with atypical phenotype. 

PMID- 24870369
TI  - Quality of life in children with cerebral palsy: implications for practice.
AB  - The ability to assess the quality of life of children with cerebral palsy to
      inform and evaluate individual care plans, service planning, interventions, and
      policies is crucial. In this article, the recent evidence on quality of life in
      children with cerebral palsy is reviewed, with attention to the determinants of
      quality of life and role of this construct as a practical outcome indicator in
      clinical trials. Quality of life measurement advances for children with cerebral
      palsy are discussed with a focus on condition-specific quality of life measures,
      particularly, the Cerebral Palsy Quality of Life-Child, which is the first
      condition-specific quality of life measure for children with cerebral palsy. The
      article presents an overview for clinicians and researchers intending to use
      quality of life measures on children with cerebral palsy and provides
      recommendations for future research that will better inform practice in the
      field. 

PMID- 24870371
TI  - Electronic and structural study of Pt-modified Au vicinal surfaces: a model
      system for Pt-Au catalysts.
AB  - Two single crystalline surfaces of Au vicinal to the (111) plane were modified
      with Pt and studied using scanning tunneling microscopy (STM) and X-ray
      photoemission spectroscopy (XPS) in ultra-high vacuum environment. The vicinal
      surfaces studied are Au(332) and Au(887) and different Pt coverage (thetaPt) were
      deposited on each surface. From STM images we determine that Pt deposits on both
      surfaces as nanoislands with heights ranging from 1 ML to 3 ML depending on
      thetaPt. On both surfaces the early growth of Pt ad-islands occurs at the lower
      part of the step edge, with Pt ad-atoms being incorporated into the steps in some
      cases. XPS results indicate that partial alloying of Pt occurs at the interface
      at room temperature and at all coverage, as suggested by the negative chemical
      shift of Pt 4f core line, indicating an upward shift of the d-band center of the
      alloyed Pt. Also, the existence of a segregated Pt phase especially at higher
      coverage is detected by XPS. Sample annealing indicates that the temperature rise
      promotes a further incorporation of Pt atoms into the Au substrate as supported
      by STM and XPS results. Additionally, the catalytic activity of different PtAu
      systems reported in the literature for some electrochemical reactions is
      discussed considering our findings. 

PMID- 24870370
TI  - The contribution of histopathological examination to the diagnosis of cervico
      facial actinomycosis: a retrospective analysis of 68 cases.
AB  - Cervico-facial actinomycosis is an infectious, suppurative, and granulomatous
      disease due to Actinomyces species. Usually, the diagnosis is confirmed by
      microbiological cultures; however, the need for careful anaerobic handling of
      specimens often makes it difficult to obtain an effective microbial growth.
      Therefore, we conducted a retrospective study on biopsy samples from patients
      with a clinical suspicion of cervico-facial actinomycosis, in order to determine
      whether accurate histopathological examination could reliably confirm the
      diagnosis. A retrospective revision of formalin-fixed, paraffin-embedded archival
      material from 68 cases of cervico-facial lesions, with negative culture for
      anaerobic/microaerophilic microorganisms, was performed. Twelve serial sections
      for each case were cut from the paraffin blocks, individually collected on
      positively charged slides to obtain good section-to-slide adhesion, and stained
      with hematoxylin and eosin (H&E) and periodic acid-Schiff (PAS).
      Histopathological examination of the serial sections allowed the identification
      of bacterial colonies consistent with actinomycetes in 22 cases (32 %). The
      proposed histopathological examination allowed the retrospective diagnosis of
      cervical actinomycosis in one-third of clinical specimens that remained
      misdiagnosed following traditional H&E examination.

PMID- 24870373
TI  - Spin dynamics of radical pairs with restricted geometries and strong exchange
      coupling: the role of hyperfine coupling.
AB  - Subnanosecond radical pair (RP) formation by electron transfer from an excited
      singlet state or by bond breaking produces two correlated spins coupled by their
      spin-spin exchange (J) and magnetic dipole (D) interactions. In the high magnetic
      field limit, the two-spin system can be described by a singlet state (S) and
      three triplet states (T0, T(+1), T(-1)). When J is small relative to the electron
      Zeeman interaction, |T0? is the only triplet state that is populated by coherent
      spin mixing with the |S? state because the |T(+1)? and |T(-1)? states are well
      separated from |S? by a large energy gap. Herein, we describe the spin dynamics
      for RPs having restricted geometries in which J is similar in magnitude to the
      electron Zeeman interaction and does not fluctuate significantly. Under these
      circumstances, depending on the sign of J, the energies of |T(+1)? or |T(-1)? are
      close to that of |S? so that weak isotropic electron-nuclear hyperfine coupling
      leads to population of |T(+1)? or |T(-1)?. An approximate relationship for the
      triplet quantum yield is developed for a RP in the large J regime, where one or
      both electrons interact with nearby spin-1/2 nuclei. This relationship also
      yields the net spin polarization transfer to the nuclear spins.

PMID- 24870372
TI  - RF microalgal lipid content characterization.
AB  - Most conventional techniques for the determination of microalgae lipid content
      are time consuming and in most cases are indirect and require excessive sample
      preparations. This work presents a new technique that utilizes radio frequency
      (RF) for rapid lipid quantification, without the need for sample preparation.
      Tests showed that a shift in the resonance frequency of a RF open-ended coaxial
      resonator and a gradual increase in its resonance magnitude may occur as the
      lipids content of microalgae cells increases. These response parameters can be
      then calibrated against actual cellular lipid contents and used for rapid
      determination of the cellular lipids. The average duration of lipid
      quantification using the proposed technique was of about 1 minute, which is
      significantly less than all other conventional techniques, and was achieved
      without the need for any time consuming treatment steps. 

PMID- 24870374
TI  - Judge tells trust it can treat minor for paracetamol overdose against her wishes.

PMID- 24870375
TI  - Human leukocyte antigen-G (HLA-G) polymorphism and expression in breast cancer
      patients.
AB  - Human leukocyte antigen-G (HLA-G) is known to be implicated in a tumor-driven
      immune escape mechanism in malignancies. The purpose of this study was to
      investigate HLA-G polymorphism and expression in breast cancer. HLA-G alleles
      were determined by direct DNA sequencing procedures from blood samples of 80
      breast cancer patients and 80 healthy controls. Soluble HLA-G (sHLA-G) was
      measured by enzyme-linked immunosorbent assay (ELISA) from serum specimens. HLA-G
      expression in breast cancer lesions was also analyzed by immunohistochemistry
      staining. The presence of HLA-G 3' untranslated region (UTR) 14-bp sequence was
      analyzed and found to be associated with reduced risk of breast cancer
      susceptibility based on HLA-G expression in tissues (P = 0.0407). Levels of sHLA
      G were higher in the breast cancer group (median 117.2 U/mL) compared to the
      control group (median 10.1 U/mL, P<0.001). The area under the receiver operating
      characteristic curve (AU-ROC) values of sHLA-G for differentiating breast cancer
      from normal controls and for detecting metastasis from other stages of breast
      cancer were 0.89 and 0.79, respectively. HLA-G polymorphism and expression may be
      involved in breast carcinogenesis and sHLA-G concentrations could be used as a
      diagnostic marker for detecting breast cancer. 

PMID- 24870378
TI  - Pleomorphic liposarcoma of the hand.

PMID- 24870376
TI  - Isolation of a stable subpopulation of mobilized dental pulp stem cells (MDPSCs)
      with high proliferation, migration, and regeneration potential is independent of
      age.
AB  - Insights into the understanding of the influence of the age of MSCs on their
      cellular responses and regenerative potential are critical for stem cell therapy
      in the clinic. We have isolated dental pulp stem cells (DPSCs) subsets based on
      their migratory response to granulocyte-colony stimulating factor (G-CSF)
      (MDPSCs) from young and aged donors. The aged MDPSCs were efficiently enriched in
      stem cells, expressing high levels of trophic factors with high proliferation,
      migration and anti-apoptotic effects compared to young MDPSCs. In contrast,
      significant differences in those properties were detected between aged and young
      colony-derived DPSCs. Unlike DPSCs, MDPSCs showed a small age-dependent increase
      in senescence-associated beta-galactosidase (SA-beta-gal) production and
      senescence markers including p16, p21, Interleukin (IL)-1beta, -6, -8, and
      Groalpha in long-term culture. There was no difference between aged and young
      MDPSCs in telomerase activity. The regenerative potential of aged MDPSCs was
      similar to that of young MDPSCs in an ischemic hindlimb model and an ectopic
      tooth root model. These results demonstrated that the stem cell properties and
      the high regenerative potential of MDPSCs are independent of age, demonstrating
      an immense utility for clinical applications by autologous cell transplantation
      in dental pulp regeneration and ischemic diseases. 

PMID- 24870379
TI  - Designed cell penetrating peptide dendrimers efficiently internalize cargo into
      cells.
AB  - Redesigning linear cell penetrating peptides (CPPs) into a multi-branched
      topology with short dipeptide branches gave cell penetrating peptide dendrimers
      (CPPDs) with higher cell penetration, lower toxicity and hemolysis and higher
      serum stability than linear CPPs. Their use is demonstrated by delivering a
      cytotoxic peptide and paclitaxel into cells. 

PMID- 24870380
TI  - Thermodynamics of 4,4'-stilbenedicarboxylic acid monolayer self-assembly at the
      nonanoic acid-graphite interface.
AB  - A direct calorimetric measurement of the overall enthalpy change associated with
      self-assembly of organic monolayers at the liquid-solid interface is for most
      systems of interest practically impossible. In previous work we proposed an
      adapted Born-Haber cycle for an indirect assessment of the overall enthalpy
      change by using terephthalic acid monolayers at the nonanoic acid-graphite
      interface as a model system. To this end, the sublimation enthalpy, dissolution
      enthalpy, the monolayer binding enthalpy in vacuum, and a dewetting enthalpy are
      combined to yield the total enthalpy change. In the present study the Born-Haber
      cycle is applied to 4,4'-stilbenedicarboxylic acid monolayers. A detailed
      comparison of these two aromatic dicarboxylic acids is used to evaluate and
      quantify the contribution of the organic backbone for stabilization of the
      monolayer at the nonanoic acid-graphite interface. 

PMID- 24870377
TI  - Co-transplantation of human hematopoietic stem cells and human breast cancer
      cells in NSG mice: a novel approach to generate tumor cell specific human
      antibodies.
AB  - Humanized tumor mice (HTM) were generated by the co-transplantation of human
      hematopoietic stem cells and human breast cancer cells overexpressing HER2 into
      neonatal NOD-scid IL2Rgamma(null) (NSG) mice. These mice are characterized by the
      development of a human immune system in combination with human breast cancer
      growth. Due to concurrent transplantation into newborn mice, transfer of MHC
      mismatched tumor cells resulted in solid coexistence and immune cell activation
      (CD4(+) T cells, natural killer cells, and myeloid cells), but without evidence
      for rejection. Histological staining of the spleen of HTM revealed co
      localization of human antigen-presenting cells together with human T and B cells
      allowing MHC-dependent interaction, and thereby the generation of T cell
      dependent antibody production. Here, we investigated the capability of these mice
      to generate human tumor-specific antibodies and correlated immunoglobulin titers
      with tumor outgrowth. We found detectable IgM and also IgG amounts in the serum
      of HTM, which apparently controlled tumor development when IgG serum
      concentrations were above 10 ug/ml. Western blot analyses revealed that the tumor
      specific antibodies generated in HTM did not recognize HER2/neu antigens, but
      different, possibly relevant antigens for breast cancer therapy. In conclusion,
      HTM offer a novel approach to generate complete human monoclonal antibodies that
      do not require further genetic manipulation (e. g., humanization) for a potential
      application in humans. In addition, efficacy and safety of the generated
      antibodies can be tested in the same mouse model under human-like conditions.
      This might be of particular interest for cancer subtypes with no currently
      available antibody therapy. 

PMID- 24870382
TI  - Clinical roundtable monograph: unmet needs in the treatment of chronic
      lymphocytic leukemia: integrating a targeted approach.
AB  - Chronic lymphocytic leukemia (CLL) is the most frequently diagnosed hematologic
      malignancy in the United States. Although several features can be useful in the
      diagnosis of CLL, the most important is the immunophenotype.Two staging systems-
      the Binet system and the Rai classification--are used to assess risk. After
      diagnosis, the first major therapeutic decision is when to initiate therapy, as a
      watchful waiting approach is often appropriate for patients with asymptomatic
      disease. Once a patient has met the criteria for treatment, the choice of therapy
      is the next major decision. Younger patients (<65 years) often receive more
      aggressive treatment that typically consists of cytotoxic chemotherapy. There is
      a great unmet need concerning treatment of older patients with CLL, who often
      present with more comorbid conditions that can decrease their ability to tolerate
      particular regimens. The current standard of care for older patients with CLL is
      rituximab plus chlorambucil. The concept of targeted agents is currently an area
      of intense interest in CLL. The Bruton's tyrosine kinase inhibitor ibrutinib is
      the targeted agent that is furthest along in clinical development. It is
      associated with an overall survival rate of 83%. Idelalisib targets the
      phosphatidyl inositol 3-kinase and is under evaluation in pivotal trials.
      Targeted agents offer much promise in terms of efficacy, toxicity, and oral
      availability. They will change the management of patients with CLL.

PMID- 24870387
TI  - Vocal fry may undermine the success of young women in the labor market.
AB  - Vocal fry is speech that is low pitched and creaky sounding, and is increasingly
      common among young American females. Some argue that vocal fry enhances speaker
      labor market perceptions while others argue that vocal fry is perceived
      negatively and can damage job prospects. In a large national sample of American
      adults we find that vocal fry is interpreted negatively. Relative to a normal
      speaking voice, young adult female voices exhibiting vocal fry are perceived as
      less competent, less educated, less trustworthy, less attractive, and less
      hirable. The negative perceptions of vocal fry are stronger for female voices
      relative to male voices. These results suggest that young American females should
      avoid using vocal fry speech in order to maximize labor market opportunities. 

PMID- 24870388
TI  - Impact on liver cancer treatment of a first erroneous diagnosis of hemangioma.
AB  - BACKGROUND: Most liver hemangioma (HA) diagnoses are presumptive and based on
      radiological features and growth trend. The goal of this study was to analyze the
      impact of a false diagnosis of hemangioma upon the overall therapeutic course and
      upon the prognosis of a liver malignancy. METHODS: Twenty-eight patients with
      liver cancer who were observed in the period 2001-2007 after an initial erroneous
      diagnosis of HA were retrospectively evaluated. We studied their radiological
      workup after blind revision of the images by two radiologists with specific
      expertise in liver imaging, analyzing the relationship between overall management
      and center volume, mean delay from the first test to the curative treatment, and
      clinical consequences of this diagnostic mistake. RESULTS: The diagnosis of false
      HA occurred in a low-volume center (LVC) in 75 % of cases. A specific risk for
      liver cancer was present in 71.4 % of patients. US gave a false diagnosis of HA
      in 25/27 patients, a CT scan in 18/25 patients, and MRI in 6/16 patients. The
      final diagnosis was reached with a mean delay of 22 months. Liver resection was
      possible in 22 patients; in the 17 hepatocellular carcinoma cases, the survival
      rate was 69.4 % at 5 years after the first observation. CONCLUSIONS: A false
      diagnosis of HA in the presence of malignancy is not rare nowadays and
      significantly reduces the chances of cure. In situations at risk of having the
      error occur (poor technical quality of imaging, low specific experience, doubtful
      diagnosis, and high-cancer-risk patient), the rationale approach is to discuss
      the case with a multidisciplinary team skilled in the field of liver cancer.

PMID- 24870389
TI  - Safe negative margin width in breast conservative therapy: results from a
      population with a high percentage of negative prognostic factors.
AB  - BACKGROUND: There remains a controversy in the literature regarding adequate
      width of negative surgical margins in breast conservative therapy (BCT). It is
      now advocated that no tumor on an inked margin is a safe negative margin.
      Majority of studies on the outcomes of BCT had patients with favorable prognostic
      factors. Pakistani population has a high expression of unfavorable prognostic
      factors. The objective of this study was to determine a safe negative margin
      width in Pakistani population that undergoes BCT. METHODS: A total of 603
      patients with identifiable surgical margins underwent BCT from 1997 to 2009 in
      Shaukat Khanum Cancer Hospital. Patients were divided into close (<=2 mm), free
      (>2-10 mm), and wide (>10 mm) margin groups. Locoregional recurrence was defined
      as recurrence within the operated breast, ipsilateral axilla, or supraclavicular
      or internal mammary lymph nodes. Locoregional recurrence-free survival was
      calculated from the date of surgery to the date of locoregional recurrence. Five
      year locoregional recurrence-free survival was determined for margin groups.
      Univariate and multivariate Cox proportional hazard analyses were performed to
      determine independent predictors of locoregional recurrence. RESULTS: A total of
      415 (69 %) patients were <50 years of age. There were 82 (15 %) T3/T4, 337 (56 %)
      poorly differentiated, and 238 (39 %) ER/PR -ve tumors. Nodal positivity was
      present in 314 (52 %) patients. The actual number of locoregional recurrences was
      16 (12 %), 8 (3 %), and 10 (4.6 %), respectively (P = 0.002). Expected 5-year
      locoregional recurrence-free survival was 90, 97, and 96 %, respectively (P =
      0.002). On multivariate analysis, tumor size, nodal involvement, and negative
      margin width were independent predictors of locoregional recurrence. CONCLUSION:
      A negative margin width of 2 mm might represent an adequate negative margin width
      in the Pakistani population undergoing breast conservative therapy.

PMID- 24870391
TI  - Boy or girl's mendelian genetics with "precious" families.

PMID- 24870390
TI  - Enhanced recovery after surgery pathway in patients undergoing
      pancreaticoduodenectomy.
AB  - BACKGROUND: Enhanced recovery after surgery (ERAS((r))) pathways have reduced
      morbidity and length of hospital stay (LOS) in orthopedics, bariatric, and
      colorectal surgery. New perioperative care protocols have been tested in patients
      undergoing pancreaticoduodenectomy (PD), with controversial results on morbidity.
      Incomplete data about ERAS items compliance have been reported. The aim of this
      study was to assess compliance with an ERAS protocol and its impact on short-term
      outcome in patients undergoing PD. METHODS: A comprehensive ERAS protocol was
      applied in 115 consecutive patients undergoing PD. Each ERAS patient was matched
      with one patient who received standard perioperative care. Match criteria were
      age, gender, malignant/benign disease, and PD-specific prognostic score. RESULTS:
      No adverse effect related to ERAS items occurred. Compliance with postoperative
      items ranged between 38 and 66 %. The ERAS group had an earlier recovery of
      mobilization (p < 0.001), oral feeding (p < 0.001), gut motility (p < 0.001), and
      an earlier suspension of intravenous fluids (p = 0.041). No difference between
      ERAS and control group was found in mortality, overall morbidity, and major
      complication rates. Subgroup analysis showed that 43/60 (71 %) patients with
      early postoperative low compliance with the ERAS pathway had complications. The
      ERAS pathway significantly shortened LOS in uneventful patients or those with
      minor complications (11.2 vs. 13.7 days, p = 0.001). CONCLUSION: The ERAS pathway
      was feasible and safe, yielding an earlier postoperative recovery. An ERAS
      protocol should be implemented in patients undergoing PD; however, patients with
      early postoperative low compliance should be carefully managed.

PMID- 24870392
TI  - Polymer ligand exchange to control stabilization and compatibilization of
      nanocrystals.
AB  - We demonstrate polymer ligand exchange to be an efficient method to control
      steric stabilization and compatibilization of nanocrystals. A rational design of
      polymer binding groups and ligand exchange conditions allows to attach polymer
      brushes with grafting densities >1 nm(-2) to inorganic nanocrystals for nearly
      any nanocrystal/polymer combination using only a few types of binding groups. We
      demonstrate the potential of the method as an alternative to established grafting
      from and grafting-to routes in considerably increasing the stabilization of
      inorganic nanocrystals in solution, to prepare completely miscible polymer
      nanocomposites with a controllable distance between nanoparticles, and to induce
      and control aggregation into percolation networks in polymeric matrices for a
      variety of different nanocrystal/polymer combinations. A dense attachment of very
      short polymer ligands is possible enabling to prepare ordered nanoparticle
      monolayers with a distance or pitch of only 7.2 nm, corresponding to a potential
      magnetic storage density of 12.4 Tb/in(2). Not only end-functionalized
      homopolymers, but also commercially available copolymers with functional
      comonomers can be used for stable ligand exchange, demonstrating the versatility
      and broad potential of the method. 

PMID- 24870393
TI  - Older widowers and postdeath encounters: a qualitative investigation.
AB  - This study examined older widowers' descriptions and interpretations of their
      postdeath encounters, including sense of presence experiences and sensory
      experiences (e.g., saw the deceased, heard the deceased's voice). Six older
      widowers who had reported at least one postdeath encounter were interviewed.
      Their responses were interpreted within a constructivist perspective. Each
      widower's explanation of the encounters generally matched his individual
      religious/spiritual worldview. The participants used both internal (e.g., "My
      mind was tricking me") and external (e.g., a sign from heaven) sources to explain
      their postdeath encounters. The author presents implications for future research.

PMID- 24870394
TI  - Reaction-induced cluster ripening and initial size-dependent reaction rates for
      CO oxidation on Pt(n)/TiO2(110)-(1*1).
AB  - We determined the CO oxidation rates for size-selected Ptn (n ? {3,7,10})
      clusters deposited onto TiO2(110). In addition, we investigated the cluster
      morphologies and their mean sizes before and after the reaction. While the
      clusters are fairly stable upon annealing in ultrahigh vacuum up to 600 K,
      increasing the temperature while adsorbing either one of the two reactants leads
      to ripening already from 430 K on. This coarsening is even more pronounced when
      both reactants are dosed simultaneously, i.e., running the CO oxidation reaction.
      Since the ripening depends on the size initially deposited, there is nevertheless
      a size effect; the catalytic activity decreases monotonically with increasing
      initial cluster size. 

PMID- 24870395
TI  - Validation of an efficient method of assigning material properties in finite
      element analysis of pelvic bone.
AB  - Bone in the pelvis is a composite material with a complex anatomical structure
      that is difficult to model computationally. Rather than assigning material
      properties to increasingly smaller elements to capture detail in three
      dimensional finite element (FE) models, properties can be assigned to Gauss
      points within larger elements. As part of a validation process, we compared
      experimental and analytical results from a composite beam under four-point load
      to FE models with material properties assigned to refined elements and Gauss
      points within larger elements. Both FE models accurately predicted deformation
      and the analytical predictions of internal shear stress. 

PMID- 24870396
TI  - Quantitative analysis of the nonlinear displacement-load behavior of the lumbar
      spine.
AB  - There is currently no universal model or fitting method to characterize the visco
      elastic behavior of the lumbar spine observed in displacement versus load
      hysteresis loops. In this study, proposed methods for fitting these loops, along
      with the metrics obtained, were thoroughly analyzed. A spline fitting technique
      was shown to provide a consistent approximation of spinal kinetic behavior that
      can be differentiated and integrated. Using this tool, previously established
      metrics were analyzed using data from two separate studies evaluating different
      motion preservation technologies. Many of the metrics, however, provided no
      significant differences beyond range of motion analysis. Particular attention was
      paid to how different definitions of the neutral zone capture the high
      flexibility region often seen in lumbar hysteresis loops. As a result, the
      maximum slope was introduced and shown to be well defined. This new parameter
      offers promise as a descriptive measurement of spinal instability in vitro and
      may have future implications in clinical diagnosis and treatment of spinal
      instability. In particular, it could help in assigning treatments to specific
      stabilizing effects in the lumbar spine.

PMID- 24870397
TI  - Carbamoyl anion addition to nitrones.
AB  - The addition of carbamoyl anions derived from N,N-disubstituted formamides and
      LDA to N-tert-butyl nitrones is described. The reaction was demonstrated with a
      variety of formamides and nitrones and provided a direct route to alpha-(N
      hydroxy)amino amides. The use of a tert-leucinol derived chiral auxiliary on the
      nitrone provided products in good diastereoselectivity. Derivatization of the
      products by tert-butyl deprotection or N-deoxygenation was demonstrated. 

PMID- 24870398
TI  - Generation of low-valent tantalum species by reversible C-H activation in a
      cyclometallated tantalum hydride complex.
AB  - The cyclometallated tantalum(v) hydride complex {ArNC(Me)CHC(Me)N[2-(CHMeCH2)-6
      (i)Pr-C6H3]}Ta(N(t)Bu)H (2) was prepared from hydrogenolysis of (BDI)TaN(t)BuMe2
      (BDI = N,N'-diaryl-beta-diketiminate, aryl = 2,6-(i)Pr2-C6H3). Based on
      mechanistic studies, formation of 2 likely proceeds through a dihydride
      intermediate generated from successive sigma-bond metathesis steps. Compound 2
      was found to undergo reductive elimination under certain conditions to form
      trivalent tantalum species. Coordination of DMAP to 2, followed by gentle heating
      under H2, gives (MAD)Ta(N(t)Bu)(NAr)(DMAP), which is produced through reductive C
      N bond cleavage of the BDI ligand in a Ta(iii) intermediate. Ta(iii) dicarbonyl
      derivatives have been accessed by either introducing CO atmosphere to the DMAP
      adduct of 2 at room temperature, or by directly adding CO to 2 at low
      temperature. 

PMID- 24870400
TI  - Measuring Mental Health Recovery: An Application of Rasch Modeling to the
      Consumer Recovery Measure.
AB  - As the need for recovery-oriented outcomes increases, it is critical to
      understand how numeric recovery scores are developed. In the current article, the
      modern Rasch modeling techniques were applied to establish numeric scores of
      consumers' perceptions of recovery. A sample of 1,973 adult consumers at a
      community-based mental health center (57.5% male; average age of 47 years old)
      completed the 15-item Consumer Recovery Measure. A confirmatory factor analysis
      revealed the unidimensional nature of the Consumer Recovery Measure and provided
      construct validity evidence. The Rasch analysis displayed that the items produced
      acceptable model fit, reliability, and identified the difficulty of the items.
      The conclusion emphasizes the value of Rasch modeling regarding the measurement
      of recovery and its relevance to consumer-derived assessments in the clinical
      decision-making process. 

PMID- 24870399
TI  - The resilience activation framework: a conceptual model of how access to social
      resources promotes adaptation and rapid recovery in post-disaster settings.
AB  - A number of governmental agencies have called for enhancing citizens' resilience
      as a means of preparing populations in advance of disasters, and as a
      counterbalance to social and individual vulnerabilities. This increasing
      scholarly, policy, and programmatic interest in promoting individual and communal
      resilience presents a challenge to the research and practice communities: to
      develop a translational framework that can accommodate multidisciplinary
      scientific perspectives into a single, applied model. The Resilience Activation
      Framework provides a basis for testing how access to social resources, such as
      formal and informal social support and help, promotes positive adaptation or
      reduced psychopathology among individuals and communities exposed to the acute
      collective stressors associated with disasters, whether human-made, natural, or
      technological in origin. Articulating the mechanisms by which access to social
      resources activate and sustain resilience capacities for optimal mental health
      outcomes post-disaster can lead to the development of effective preventive and
      early intervention programs. 

PMID- 24870401
TI  - Genome-wide analysis and identification of stress-responsive genes of the CCCH
      zinc finger family in Solanum lycopersicum.
AB  - Zinc finger genes comprise a large and diverse gene family. Based on their
      individual finger structures and spacing, zinc finger proteins are further
      divided into different families according to their specific molecular functions.
      Genes in the CCCH family encode zinc finger proteins containing a motif with
      three cysteines and one histidine. They play important roles in plant growth and
      development, and in response to biotic and abiotic stresses. However, the limited
      analysis of the genome sequence has meant that there is no detailed information
      concerning the CCCH zinc finger family in tomato (Solanum lycopersicum). Here, we
      identified 80 CCCH zinc finger protein genes in the tomato genome. A complete
      overview of this gene family in tomato was presented, including the chromosome
      locations, gene duplications, phylogeny, gene structures and protein motifs.
      Promoter sequences and expression profiles of putative stress-responsive members
      were also investigated. These results revealed that, with the exception of four
      genes, the 80 CCCH genes are distributed over all 12 chromosomes with different
      densities, and include six segmental duplication events. The CCCH family in
      tomato could be divided into 12 groups based on their different CCCH motifs and
      into eight subfamilies by phylogenetic analysis. Analysis showed that almost all
      CCCH genes contain putative stress-responsive cis-elements in their promoter
      regions. Nine CCCH genes chosen for further quantitative real-time PCR analysis
      showed differential expression patterns in three representative tomato tissues.
      In addition, their expression levels indicated that these genes are mostly
      involved in the response to mannitol, heat, salicylic acid, ethylene or methyl
      jasmonate treatments. To the best of our knowledge, this is the first report of a
      genome-wide analysis of the tomato CCCH zinc finger family. Our data provided
      valuable information on tomato CCCH proteins and form a foundation for future
      studies of these proteins, especially for those members that may play important
      roles in stress responses. 

PMID- 24870402
TI  - Oblique orientation discrimination thresholds are superior in those with a high
      level of autistic traits.
AB  - Enhanced low-level perception, although present in individuals with autism, is
      not seen in individuals with high, but non-clinical, levels of autistic traits
      (Brock et al.in Percept Lond 40(6):739. doi: 10.1068/p6953 , 2011). This is
      surprising, as many of the higher-level visual differences found in autism have
      been shown to correlate with autistic traits in non-clinical samples. Here we
      measure vertical-oblique and, more difficult, oblique-oblique orientation
      discrimination thresholds in a non-clinical sample. As predicted, oblique-oblique
      thresholds provided a more sensitive test of orientation discrimination, and were
      negatively related to autistic traits (N = 94, r = -.356, p < .0001). We conclude
      that individual differences in orientation discrimination and autistic traits are
      related, and suggest that both of these factors could be mediated by increased
      levels of the inhibitory neurotransmitter GABA.

PMID- 24870403
TI  - Transformation of pristine and citrate-functionalized CeO2 nanoparticles in a
      laboratory-scale activated sludge reactor.
AB  - Engineered nanomaterials (ENMs) are used to enhance the properties of many
      manufactured products and technologies. Increased use of ENMs will inevitably
      lead to their release into the environment. An important route of exposure is
      through the waste stream, where ENMs will enter wastewater treatment plants
      (WWTPs), undergo transformations, and be discharged with treated effluent or
      biosolids. To better understand the fate of a common ENM in WWTPs, experiments
      with laboratory-scale activated sludge reactors and pristine and citrate
      functionalized CeO2 nanoparticles (NPs) were conducted. Greater than 90% of the
      CeO2 introduced was observed to associate with biosolids. This association was
      accompanied by reduction of the Ce(IV) NPs to Ce(III). After 5 weeks in the
      reactor, 44 +/- 4% reduction was observed for the pristine NPs and 31 +/- 3% for
      the citrate-functionalized NPs, illustrating surface functionality dependence.
      Thermodynamic arguments suggest that the likely Ce(III) phase generated would be
      Ce2S3. This study indicates that the majority of CeO2 NPs (>90% by mass) entering
      WWTPs will be associated with the solid phase, and a significant portion will be
      present as Ce(III). At maximum, 10% of the CeO2 will remain in the effluent and
      be discharged as a Ce(IV) phase, governed by cerianite (CeO2). 

PMID- 24870404
TI  - A novel pathway for arsenic elimination: human multidrug resistance protein 4
      (MRP4/ABCC4) mediates cellular export of dimethylarsinic acid (DMAV) and the
      diglutathione conjugate of monomethylarsonous acid (MMAIII).
AB  - Hundreds of millions of people worldwide are exposed to unacceptable levels of
      arsenic in drinking water. This is a public health crisis because arsenic is a
      Group I (proven) human carcinogen. Human cells methylate arsenic to
      monomethylarsonous acid (MMA(III)), monomethylarsonic acid (MMA(V)),
      dimethylarsinous acid (DMA(III)), and dimethylarsinic acid (DMA(V)). Although the
      liver is the predominant site for arsenic methylation, elimination occurs mostly
      in urine. The protein(s) responsible for transport of arsenic from the liver
      (into blood), ultimately for urinary elimination, are unknown. Human multidrug
      resistance protein 1 (MRP1/ABCC1) and MRP2 (ABCC2) are established arsenic efflux
      pumps, but unlike the related MRP4 (ABCC4) are not present at the basolateral
      membrane of hepatocytes. MRP4 is also found at the apical membrane of renal
      proximal tubule cells, making it an ideal candidate for urinary arsenic
      elimination. In the current study, human MRP4 expressed in HEK293 cells reduced
      the cytotoxicity and cellular accumulation of arsenate, MMA(III), MMA(V),
      DMA(III), and DMA(V) while two other hepatic basolateral MRPs (MRP3 and MRP5) did
      not. Transport studies with MRP4-enriched membrane vesicles revealed that the
      diglutathione conjugate of MMA(III), monomethylarsenic diglutathione
      [MMA(GS)(2)], and DMA(V) were the transported species. MMA(GS)(2) and DMA(V)
      transport was osmotically sensitive, allosteric (Hill coefficients of 1.4 +/- 0.2
      and 2.9 +/- 1.2, respectively), and high affinity (K0.5 of 0.70 +/- 0.16 and 0.22
      +/- 0.15 MUM, respectively). DMA(V) transport was pH-dependent, with highest
      affinity and capacity at pH 5.5. These results suggest that human MRP4 could be a
      major player in the elimination of arsenic.

PMID- 24870405
TI  - Molecular mechanisms of methoctramine binding and selectivity at muscarinic
      acetylcholine receptors.
AB  - Methoctramine (N,N'-bis[6-[[(2-methoxyphenyl)-methyl]hexyl]-1,8-octane] diamine)
      is an M(2)-selective competitive antagonist of muscarinic acetylcholine receptors
      and exhibits allosteric properties at high concentrations. To reveal the
      molecular mechanisms of methoctramine binding and selectivity we took advantage
      of reciprocal mutations of the M(2) and M(3) receptors in the second and third
      extracellular loops that are involved in the binding of allosteric ligands. To
      this end we performed measurements of kinetics of the radiolabeled antagonists N
      methylscopolamine (NMS) in the presence of methoctramine and its precursors,
      fluorescence energy transfer between green fluorescent protein-fused receptors
      and an Alexa-555-conjugated precursor of methoctramine, and simulation of
      molecular dynamics of methoctramine association with the receptor. We confirm the
      hypothesis that methoctramine high-affinity binding to the M(2) receptors
      involves simultaneous interaction with both the orthosteric binding site and the
      allosteric binding site located between the second and third extracellular loops.
      Methoctramine can bind solely with low affinity to the allosteric binding site on
      the extracellular domain of NMS-occupied M(2) receptors by interacting primarily
      with glutamate 175 in the second extracellular loop. In this mode, methoctramine
      physically prevents dissociation of NMS from the orthosteric binding site. Our
      results also demonstrate that lysine 523 in the third extracellular loop of the
      M(3) receptors forms a hydrogen bond with glutamate 219 of the second
      extracellular loop that hinders methoctramine binding to the allosteric site at
      this receptor subtype. Impaired interaction with the allosteric binding site
      manifests as low-affinity binding of methoctramine at the M(3) receptor.

PMID- 24870406
TI  - Complex pharmacology of novel allosteric free fatty acid 3 receptor ligands.
AB  - Analysis of the roles of the short chain fatty acid receptor, free fatty acid 3
      receptor (FFA3), has been severely limited by the low potency of its endogenous
      ligands, the crossover of function of these on the closely related free fatty
      acid 2 receptor, and a dearth of FFA3-selective synthetic ligands. From a series
      of hexahydroquinolone-3-carboxamides, we demonstrate that 4-(furan-2-yl)-2-methyl
      5-oxo-N-(o-tolyl)-1,4,5,6,7,8-hexahydroquinoline-3-carboxamide is a selective and
      moderately potent positive allosteric modular (PAM)-agonist of the FFA3 receptor.
      Modest chemical variations within this series resulted in compounds completely
      lacking activity, acting as FFA3 PAMs, or appearing to act as FFA3-negative
      allosteric modulators. However, the pharmacology of this series was further
      complicated in that certain analogs displaying overall antagonism of FFA3
      function actually appeared to generate their effects via a combined positive
      allosteric binding cooperativity and negative allosteric effect on orthosteric
      ligand maximal signaling response. These studies show that various PAM-agonist
      and allosteric modulators of FFA3 can be identified and characterized. However,
      within the current chemical series, considerable care must be taken to define the
      pharmacological characteristics of specific compounds before useful predictions
      of their activity and their use in defining specific roles of FFA3 in either in
      vitro and in vivo settings can be made. 

PMID- 24870407
TI  - Noise-induced hearing loss in Korean workers: co-exposure to organic solvents and
      heavy metals in nationwide industries.
AB  - BACKGROUND: Noise exposure is a well-known contributor to work-related hearing
      loss. Recent biological evidence suggests that exposure to ototoxic chemicals
      such as organic solvents and heavy metals may be additional contributors to
      hearing loss. However, in industrial settings, it is difficult to determine the
      risks of hearing loss due to these chemicals in workplaces accompanied by
      excessive noise exposure. A few studies suggest that the effect of noise may be
      enhanced by ototoxic chemicals. Therefore, this study investigated whether co
      exposure to organic solvents and/or heavy metals in the workplace modifies the
      risk of noise exposure on hearing loss in a background of excessive noise.
      METHODS: We examined 30,072 workers nationwide in a wide range of industries from
      the Korea National Occupational Health Surveillance 2009. Data on industry-based
      exposure (e.g., occupational noise, heavy metals, and organic solvents) and
      subject-specific health outcomes (e.g., audiometric examination) were collected.
      Noise was measured as the daily 8-h time-weighted average level. Air conduction
      hearing thresholds were measured from 0.5 to 6 kHz, and pure-tone averages (PTA)
      (i.e., means of 2, 3, and 4 kHz) were computed. RESULTS: In the multivariate
      linear model, PTA increment with occupational noise were 1.64-fold and 2.15-fold
      higher in individuals exposed to heavy metals and organic solvents than in
      unexposed individuals, respectively. CONCLUSION: This study provides nationwide
      evidence that co-exposure to heavy metals and/or organic solvents may exacerbate
      the effect of noise exposure on hearing loss in workplaces. These findings
      suggest that workers in industries dealing with heavy metals or organic solvents
      are susceptible to such risks.

PMID- 24870408
TI  - Prognostic significance of CD26 in patients with colorectal cancer.
AB  - BACKGROUND: CD26, dipeptidyl peptidase IV, was discovered firstly as a membrane
      associated peptidase on the surface of leukocyte. We previously demonstrated that
      a subpopulation of CD26+ cells were associated with the development of distant
      metastasis, enhanced invasiveness and chemoresistance in colorectal cancer (CRC).
      In order to understand the clinical impact of CD26, the expression was
      investigated in CRC patient's specimens. This study investigated the prognostic
      significance of tumour CD26 expression in patients with CRC. Examination of CD26+
      cells has significant clinical impact for the prediction of distant metastasis
      development in colorectal cancer, and could be used as a selection criterion for
      further therapy. METHODS: Tumour CD26 expression levels were studied by
      immunohistochemistry using Formalin-fixed paraffin embedded (FFPE) tissues in 143
      patients with CRC. Tumour CD26 expression levels were correlated with
      clinicopathological features of the CRC patients. The prognostic significance of
      tumour tissue CD26 expression levels was assessed by univariate and multivariate
      analyses. RESULT: CD26 expression levels in CRC patients with distant metastasis
      were significantly higher than those in non-metastatic. High expression levels of
      CD26 were significantly associated with advanced tumour staging. Patients with a
      high CD26 expression level had significantly worse overall survival than those
      with a lower level (p<0.001). CONCLUSIONS: The expression of CD26 was positively
      associated with clinicopathological correlation such as TNM staging, degree of
      differentiation and development of metastasis. A high CD26 expression level is a
      predictor of poor outcome after resection of CRC. CD26 may be a useful prognostic
      marker in patients with CRC.

PMID- 24870409
TI  - The meiosis-specific modification of mammalian telomeres.
AB  - During meiosis, rapid chromosome movements within the nucleus enable homologous
      chromosomes to acquire physical juxtaposition. In most organisms, chromosome
      ends, telomeres, tethered to the transmembrane LINC-complex mediate this movement
      by transmitting cytoskeletal forces to the chromosomes. While the majority of
      molecular studies have been performed using lower eukaryotes as model systems,
      recent studies have identified mammalian meiotic telomere regulators, including
      the LINC-complex SUN1/KASH5 and the meiosis-specific telomere binding protein
      TERB1. This review highlights the molecular regulations of mammalian meiotic
      telomeres in comparison with other model systems and discusses some future
      perspectives. 

PMID- 24870411
TI  - Near-infrared low-level laser stimulation of telocytes from human myometrium.
AB  - Telocytes (TCs) are a brand-new cell type frequently observed in the interstitial
      space of many organs (see www.telocytes.com ). TCs are defined by very long (tens
      of micrometers) and slender prolongations named telopodes. At their level,
      dilations-called podoms (~300 nm), alternate with podomers (80-100 nm). TCs were
      identified in a myometrial interstitial cell culture based on morphological
      criteria and by CD34 and PDGF receptor alpha (PDGFRalpha) immunopositivity.
      However, the mechanism(s) of telopodes formation and/or elongation and
      ramification is not known. We report here the low-level laser stimulation (LLLS)
      using a 1,064-nm neodymium-doped yttrium aluminum garnet (Nd:YAG) laser (with an
      output power of 60 mW) of the telopodal lateral extension (TLE) growth in cell
      culture. LLLS of TCs determines a higher growth rate of TLE in pregnant
      myometrium primary cultures (10.3 +/- 1.0 MUm/min) compared to nonpregnant ones
      (6.6 +/- 0.9 MUm/min). Acute exposure (30 min) of TCs from pregnant myometrium to
      1 MUM mibefradil, a selective inhibitor of T-type calcium channels, determines a
      significant reduction in the LLLS TLE growth rate (5.7 +/- 0.8 MUm/min) compared
      to LLLS per se in same type of samples. Meanwhile, chronic exposure (24 h)
      completely abolishes the LLLS TLE growth in both nonpregnant and pregnant
      myometria. The initial direction of TLE growth was modified by LLLS, the angle of
      deviation being more accentuated in TCs from human pregnant myometrium than in
      TCs from nonpregnant myometrium. In conclusion, TCs from pregnant myometrium are
      more susceptible of reacting to LLLS than those from nonpregnant myometrium.
      Therefore, some implications are emerging for low-level laser therapy (LLLT) in
      uterine regenerative medicine. 

PMID- 24870410
TI  - Achieving peptide binding specificity and promiscuity by loops: case of the
      forkhead-associated domain.
AB  - The regulation of a series of cellular events requires specific protein-protein
      interactions, which are usually mediated by modular domains to precisely select a
      particular sequence from diverse partners. However, most signaling domains can
      bind to more than one peptide sequence. How do proteins create promiscuity from
      precision? Moreover, these complex interactions typically occur at the interface
      of a well-defined secondary structure, alpha helix and beta sheet. However, the
      molecular recognition primarily controlled by loop architecture is not fully
      understood. To gain a deep understanding of binding selectivity and promiscuity
      by the conformation of loops, we chose the forkhead-associated (FHA) domain as
      our model system. The domain can bind to diverse peptides via various loops but
      only interact with sequences containing phosphothreonine (pThr). We applied
      molecular dynamics (MD) simulations for multiple free and bound FHA domains to
      study the changes in conformations and dynamics. Generally, FHA domains share a
      similar folding structure whereby the backbone holds the overall geometry and the
      variety of sidechain atoms of multiple loops creates a binding surface to target
      a specific partner. FHA domains determine the specificity of pThr by well
      organized binding loops, which are rigid to define a phospho recognition site.
      The broad range of peptide recognition can be attributed to different
      arrangements of the loop interaction network. The moderate flexibility of the
      loop conformation can help access or exclude binding partners. Our work provides
      insights into molecular recognition in terms of binding specificity and
      promiscuity and helpful clues for further peptide design. 

PMID- 24870412
TI  - Economic and environmental benefits of higher-octane gasoline.
AB  - We quantify the economic and environmental benefits of designing U.S. light-duty
      vehicles (LDVs) to attain higher fuel economy by utilizing higher octane (98 RON)
      gasoline. We use engine simulations, a review of experimental data, and drive
      cycle simulations to estimate the reduction in fuel consumption associated with
      using higher-RON gasoline in individual vehicles. Lifecycle CO2 emissions and
      economic impacts for the U.S. LDV fleet are estimated based on a linear
      programming refinery model, a historically calibrated fleet model, and a well-to
      wheels emissions analysis. We find that greater use of high-RON gasoline in
      appropriately tuned vehicles could reduce annual gasoline consumption in the U.S.
      by 3.0-4.4%. Accounting for the increase in refinery emissions from production of
      additional high-RON gasoline, net CO2 emissions are reduced by 19-35 Mt/y in 2040
      (2.5-4.7% of total direct LDV CO2 emissions). For the strategies studied, the
      annual direct economic benefit is estimated to be $0.4-6.4 billion in 2040, and
      the annual net societal benefit including the social cost of carbon is estimated
      to be $1.7-8.8 billion in 2040. Adoption of a RON standard in the U.S. in place
      of the current antiknock index (AKI) may enable refineries to produce larger
      quantities of high-RON gasoline. 

PMID- 24870414
TI  - Small falls in weight can improve health provided they are long term, says NICE.

PMID- 24870413
TI  - Evaluating a web-based clinical decision support system for language disorders
      screening in a nursery school.
AB  - BACKGROUND: Early and effective identification of developmental disorders during
      childhood remains a critical task for the international community. The second
      highest prevalence of common developmental disorders in children are language
      delays, which are frequently the first symptoms of a possible disorder.
      OBJECTIVE: This paper evaluates a Web-based Clinical Decision Support System
      (CDSS) whose aim is to enhance the screening of language disorders at a nursery
      school. The common lack of early diagnosis of language disorders led us to deploy
      an easy-to-use CDSS in order to evaluate its accuracy in early detection of
      language pathologies. This CDSS can be used by pediatricians to support the
      screening of language disorders in primary care. METHODS: This paper details the
      evaluation results of the "Gades" CDSS at a nursery school with 146 children, 12
      educators, and 1 language therapist. The methodology embraces two consecutive
      phases. The first stage involves the observation of each child's language
      abilities, carried out by the educators, to facilitate the evaluation of language
      acquisition level performed by a language therapist. Next, the same language
      therapist evaluates the reliability of the observed results. RESULTS: The Gades
      CDSS was integrated to provide the language therapist with the required clinical
      information. The validation process showed a global 83.6% (122/146) success rate
      in language evaluation and a 7% (7/94) rate of non-accepted system decisions
      within the range of children from 0 to 3 years old. The system helped language
      therapists to identify new children with potential disorders who required further
      evaluation. This process will revalidate the CDSS output and allow the
      enhancement of early detection of language disorders in children. The system does
      need minor refinement, since the therapists disagreed with some questions from
      the CDSS knowledge base (KB) and suggested adding a few questions about speech
      production and pragmatic abilities. The refinement of the KB will address these
      issues and include the requested improvements, with the support of the experts
      who took part in the original KB development. CONCLUSIONS: This research
      demonstrated the benefit of a Web-based CDSS to monitor children's
      neurodevelopment via the early detection of language delays at a nursery school.
      Current next steps focus on the design of a model that includes pseudo auto
      learning capacity, supervised by experts.

PMID- 24870415
TI  - Appraisals can build resilience.
AB  - One of the matters up for discussion at RCN congress this month concerns whether
      nurse managers and leaders have the necessary resilience to lead. We have taken
      the opportunity in this issue of Nursing Management to preview the debate ( page
      8 ). As you can read, some senior nurses think that having resilience is as
      important as having integrity and the ability to inspire. 

PMID- 24870416
TI  - Better results for NHS quality of care across whole of UK.
AB  - The nuffield Trust and Health Foundation have published their assessment of NHS
      quality of care in all four UK countries since devolution.

PMID- 24870417
TI  - NMC enters second stage of consultation.
AB  - Senior nurses have until the middle of August to respond to the latest
      consultation by the Nursing and Midwifery Council (NMC) on revising its code and
      implementing revalidation.

PMID- 24870420
TI  - Pride in Nightingale legacy shines at Westminster Abbey.
AB  - More than 2,000 people attended the annual Florence Nightingale commemoration
      service at Westminster Abbey, London, last month.

PMID- 24870419
TI  - Improvement in reporting of safety incidents revealed.
AB  - Staff in England are improving how they recognise and report patient safety
      incidents, according to figures from the National Reporting and Learning System
      (NRLS). The statistics cover the period between April 1 and September 30 last
      year, and show a 9% increase in the number of incidents reported compared to the
      same period in the previous year.

PMID- 24870421
TI  - Healthcare assistant certificate could include patients' views.
AB  - Patients could be asked their views on whether healthcare workers are fit to work
      unsupervised as part of a care certificate being launched this summer.

PMID- 24870422
TI  - At-a-glance tracking system speeds up information sharing.
AB  - Hospitals in Scotland are said to be benefitting from L2.2 million in additional
      funding to track patients digitally.

PMID- 24870423
TI  - What does it take to cope with the pressures of work?
AB  - Nursing leaders are always busy. Balancing pressures, demands and
      responsibilities is part of their work. How effectively they can cope is often
      described as how resilient they are.

PMID- 24870424
TI  - 'Being a nurse leader is a tough role'.
AB  - I often hear about the concerns of nurse leaders who work at ward manager level
      or equivalent in the NHS and independent sectors. They report feeling threatened
      and having difficulty meeting the diverse challenges of their roles.

PMID- 24870425
TI  - Compassionate care for women who miscarry.
AB  - Miscarriage specialist nurse Annmaria Ellard can still remember the exact date
      she started her nurse training at the now-closed Walton Hospital, Liverpool:
      September 13 1982.

PMID- 24870426
TI  - A positive culture brings success.
AB  - In today's complex healthcare environment, it is essential to support newly
      qualified nurses and those making the transition into new nursing roles, as well
      as nurses already in practice.

PMID- 24870428
TI  - International outlook - German and UK nurses can learn from each other.
AB  - The RCN recently hosted a colleague, Andrea Weskamm, from our counterpart
      organisation in Germany, Deutsche Berufsverband fur Pflegeberufe, who had come to
      the UK to look at advanced roles for nursing in this country.

PMID- 24870430
TI  - Vantage point - developing leaders.
AB  - For nursing to develop, leadership is the one constant factor that can influence
      the quality of outcomes such as patient care and job satisfaction.

PMID- 24870434
TI  - It's the skill mix not the numbers.
AB  - In the February issue of Nursing Management, chief nurse at Guy's and St Thomas'
      NHS Foundation Trust, London, Eileen Sills is reported as expressing fears that
      having staffing levels posted at ward entrances heightens patients' anxiety. Her
      concerns raise a number of issues. Anxiety about displaying nurse-to-patient
      ratios (NPRs) on the ward reminds me of similar discussions in the past about
      whether patients and their relatives should be told if they had cancer. Sometimes
      relatives were told, but not the patients, because 'they would not be able to
      cope'.

PMID- 24870436
TI  - Out for consultation.
AB  - Preventing falls A falls prevention strategy from the Scottish Government
      outlines a 'framework for action' in the prevention and management of falls in
      the community. The strategy describes in detail four actions required to meet the
      minimum standards for falls prevention: supporting health improvement and self
      management to reduce patients' risk of having a fall; identifying high risk
      individuals; responding to people who have fallen and require immediate
      assistance; and co-ordinated management and specialist assessment. The document
      also includes a measurement plan to support services and teams in tracking their
      progress at implementing the framework. To read and comment on the framework
      before June 16, go to tinyurl.com/p4e54ug. 

PMID- 24870439
TI  - A leadership framework to support the use of e-learning resources.
AB  - Recognition needs to be given to emerging postgraduate nursing students' status
      of 'consumer', and the challenge for nurse education is to remain relevant and
      competitive in a consumer-led market. An e-learning model has been suggested as a
      competitive and contemporary way forward for student consumers, but successful
      introduction of this requires leadership and strong organisational management
      systems. This article applies the NHS leadership framework to nurse education in
      relation to implementation of e-learning and describes and interprets each
      element for application in higher education settings. By applying a leadership
      framework that acknowledges the skills and abilities of staff and encourages the
      formation of collaborative partnerships in the wider university community,
      educators can begin to develop skills and confidence in teaching using e-learning
      resources. 

PMID- 24870438
TI  - Shadowing: a central component of patient and family-centred care.
AB  - Patient and family-centred care (PFCC), as distinct from patient-centred, or
      patient-focused, care, enables healthcare organisations to work collaboratively
      with patients and their families to enhance and improve their care experiences.
      Liverpool Heart and Chest Hospital NHS Foundation Trust has implemented a PFCC
      model that is supported by a number of strategies including 'shadowing', which
      involves closely following patients and their families throughout their care
      experiences. This article briefly describes PFCC and discusses how shadowing
      works and the benefits of the process. 

PMID- 24870440
TI  - Role development: barriers, enablers and the function of a national organisation.
AB  - Successful implementation of any role development relies on strong partnership
      working between employers, managers, education providers and clinicians in the
      short and longer term to ensure sustainability. Drawing on the experience of NHS
      Education for Scotland (NES), this article highlights how one national
      organisation has supported role development. The article also explores enablers
      and barriers to proposed workforce changes and the education and learning
      considerations required for role development. It then outlines the contribution
      made by NES in providing national guidance for role development to support
      managers and individual practitioners. 

PMID- 24870441
TI  - Serving up good care.
AB  - Broadcaster AND former BBC MasterChef TV show presenter Loyd Grossman and NHS
      England senior nurse Caroline Lecko share a surprising bond.

PMID- 24870443
TI  - In Alzheimer's disease, hypometabolism in low-amyloid brain regions may be a
      functional consequence of pathologies in connected brain regions.
AB  - In patients with Alzheimer's disease (AD), prominent hypometabolism has been
      observed in brain regions with minor amyloid load. These hypometabolism-only (HO)
      areas cannot be explained merely as a consequence of local amyloid toxicity. The
      aim of this multimodal imaging study was to explore whether such HO phenomenon
      may be related to pathologies in functionally connected, remote brain regions.
      Nineteen AD patients and 15 matched controls underwent examinations with
      [(11)C]PiB-PET and [(18)F]FDG-PET. Voxel-based statistical group comparisons were
      performed to obtain maps of significantly elevated amyloid burden and reduced
      cerebral glucose metabolism, respectively, in patients. An HO area was identified
      by subtraction of equally thresholded result maps (hypometabolism minus amyloid
      burden). To identify the network typically functionally connected to this HO
      area, it was used as a seed region for a functional connectivity analysis in
      resting-state functional magnetic resonance imaging data of 17 elderly healthy
      controls. The resulting intrinsic connectivity network (HO-ICN) was retransferred
      into the brains of AD patients to be able to analyze pathologies within this
      network in the positron emission tomography (PET) datasets. The most prominent HO
      area was detected in the left middle frontal gyrus of AD patients. The HO-ICN in
      healthy controls showed a major overlap with brain areas significantly affected
      by both amyloid deposition and hypometabolism in patients. This association was
      substantiated by the results of region-of-interest-based and voxel-wise
      correlation analyses, which revealed strong correlations between the degree of
      hypometabolism within the HO region and within the HO-ICN. These results support
      the notion that hypometabolism in brain regions not strongly affected by
      locoregional amyloid pathology may be related to ongoing pathologies in remote
      but functionally connected regions, that is, by reduced neuronal input from these
      regions.

PMID- 24870444
TI  - Neuraminidase substrate promiscuity permits a mutant Micromonospora viridifaciens
      enzyme to synthesize artificial carbohydrates.
AB  - Mutation of the nucleophilic amino acid residue tyrosine to the small nonpolar
      residue glycine (Y370G) in the active site of Micromonospora viridifaciens
      neuraminidase (MvNA) produces an efficient catalyst for the transfer of N
      acetylneuraminic acid from an artificial substrate (i.e., phenyl N-acetyl-beta-D
      neuraminide) to a sugar acceptor (e.g., D-lactose, D-glucose, D-mannose, D
      raffinose, D-allose, or D-fructose) to give N-acetyl-alpha-neuraminide coupled
      carbohydrate products. In addition, this mutant enzyme (MvNA Y370G) catalyzes the
      transfer of a sugar residue from the artificial substrate 2-fluorophenyl N-acetyl
      beta-D-neuraminide to methyl glycopyranoside acceptors. Interestingly, when trans
      glycosylation reactions are conducted in aqueous solutions containing 30% (v/v)
      acetonitrile, the alpha-anomeric acceptors of methyl glucopyranoside and
      galactopyranoside generate higher product yields than do their corresponding beta
      anomers. Specifically, a 64 h reaction with 2-fluorophenyl N-acetyl-beta-D
      neuraminide as the limiting reagent and the acceptors methyl alpha-d
      galactopyranoside, methyl alpha-D-glucopyranoside, or methyl alpha-D
      mannopyranoside gives trans-glycosylation product yields of 22%, 31%, or 34%,
      respectively. With methyl alpha-D-galactopyranoside as the acceptor, trans
      glycosylations catalyzed by both MvNA Y370G and a 2,6-sialyltransferase yield
      identical products, which we identified as methyl N-acetyl-alpha-D-neuraminyl-(2 
      > 6)-alpha-D-galactopyranoside. The MvNA Y370G-catalyzed coupling of N
      acetylneuraminic acid to these three methyl alpha-d-glycopyranoside acceptors is
      favored by factors of 18-27-fold over the competing hydrolysis reaction. These
      coupling efficiencies likely arise from nonselective interactions between the
      acceptor glycopyranoside and MvNA Y370G, which preferentially places a
      carbohydrate hydroxyl group rather than water in close proximity to the active
      site where this functionality intercepts the nascent neuraminyl oxacarbenium ion
      that is formed during cleavage of the glycosidic bond in the aryl N-acetyl-beta-D
      neuraminide donor. The ability to transfer N-acetylneuraminic acid from a stable
      and readily accessible donor to acceptor carbohydrates that are not substrates
      for sialyltransferases is one step on the path for the production of pseudohuman
      glycoproteins from nonmammalian cell lines.

PMID- 24870442
TI  - High-precision distribution of highly stable optical pulse trains with 8.8 * 10
      19 instability.
AB  - The high-precision distribution of optical pulse trains via fibre links has had a
      considerable impact in many fields. In most published work, the accuracy is still
      fundamentally limited by unavoidable noise sources, such as thermal and shot
      noise from conventional photodiodes and thermal noise from mixers. Here, we
      demonstrate a new high-precision timing distribution system that uses a highly
      precise phase detector to obviously reduce the effect of these limitations.
      Instead of using photodiodes and microwave mixers, we use several fibre Sagnac
      loop-based optical-microwave phase detectors (OM-PDs) to achieve optical
      electrical conversion and phase measurements, thereby suppressing the sources of
      noise and achieving ultra-high accuracy. The results of a distribution experiment
      using a 10-km fibre link indicate that our system exhibits a residual instability
      of 2.0 * 10(-15) at1 s and8.8 * 10(-19) at 40,000 s and an integrated timing
      jitter as low as 3.8 fs in a bandwidth of 1 Hz to 100 kHz. This low instability
      and timing jitter make it possible for our system to be used in the distribution
      of optical-clock signals or in applications that require extremely accurate
      frequency/time synchronisation.

PMID- 24870445
TI  - Effect of metal precursor on the growth and electrochemical sensing properties of
      Pt-Ag nanoboxes.
AB  - Pt-Ag nanoboxes prepared using a Pt(4+) versus Pt(2+) precursor show not only
      stoichiometric, but also catalytic effects on the nanobox growth, resulting in
      metal content and surface morphology differences. Electrochemical studies on
      these nanoboxes reveal the combined importance of composition and hollow, rough
      walled nanostructure for improved detection of electroactive molecules.

PMID- 24870446
TI  - Comparison of SGA oral medications and a long-acting injectable SGA: the
      PROACTIVE study.
AB  - Until relatively recently, long-acting injectable (LAI) formulations were only
      available for first-generation antipsychotics and their utilization decreased as
      use of oral second-generation antipsychotics (SGA) increased. Although registry
      based naturalistic studies show LAIs reduce rehospitalization more than oral
      medications in clinical practice, this is not seen in recent randomized clinical
      trials. PROACTIVE (Preventing Relapse Oral Antipsychotics Compared to Injectables
      Evaluating Efficacy) relapse prevention study incorporated efficacy and
      effectiveness features. At 8 US academic centers, 305 patients with schizophrenia
      or schizoaffective disorder were randomly assigned to LAI risperidone (LAI-R) or
      physician's choice oral SGAs. Patients were evaluated during the 30-month study
      by masked, centralized assessors using 2-way video, and monitored biweekly by on
      site clinicians and assessors who knew treatment assignment. Relapse was
      evaluated by a masked Relapse Monitoring Board. Differences between LAI-R and
      oral SGA treatment in time to first relapse and hospitalization were not
      significant. Psychotic symptoms and Brief Psychiatric Rating Scale total score
      improved more in the LAI-R group. In contrast, the LAI group had higher Scale for
      Assessment of Negative Symptoms Alogia scale scores. There were no other between
      group differences in symptoms or functional improvement. Despite the advantage
      for psychotic symptoms, LAI-R did not confer an advantage over oral SGAs for
      relapse or rehospitalization. Biweekly monitoring, not focusing specifically on
      patients with demonstrated nonadherence to treatment and greater flexibility in
      changing medication in the oral treatment arm, may contribute to the inability to
      detect differences between LAI and oral SGA treatment in clinical trials. 

PMID- 24870449
TI  - Clinical utility of antithrombotic prophylaxis in ART procedures: an Italian
      experience.
AB  - BACKGROUND: The usefulness of antithrombotic prophylaxis in management of
      Assisted Reproductive Technologies (ART) is questionable. OBJECTIVES: We
      prospectively examined the contribution of an antithrombotic prophylaxis in
      influencing clinical pregnancy and live-birth in an unselected cohort of women
      approaching ART. PATIENTS/METHODS: 1107 women with fertility problems and a valid
      indication for ART were recruited. Baseline and follow-up information of
      obstetric outcomes and antithrombotic treatment were collected. RESULTS AND
      CONCLUSIONS: Median follow-up time was 34.5 months (range: 2-143). During the
      follow-up period, 595 (53.8%) women underwent ART (total 1234 cycles); 202
      (33.9%) women achieved a pregnancy for a total of 255 clinical pregnancies. The
      concomitant use of LMWH and aspirin was significantly associated with a higher
      rate of clinical pregnancies (p: 0.003, OR: 4.9, 95% CI: 1.7-14.2). The pregnancy
      rate was also significantly increased by the use of LMWH alone (p: 0.005, OR:
      2.6, 95% CI: 1.3-5.0). Carriership of inherited or acquired thrombophilia did not
      affect clinical outcomes of the ART. The efficacy of antithrombotic treatment was
      confirmed when the outcome " live-birth" was considered. Present data suggest a
      potential benefit of antithrombotic prophylaxis during ART in improving the
      number of live-births.

PMID- 24870447
TI  - Neurodevelopmental and neurodegenerative models of schizophrenia: white matter at
      the center stage.
AB  - Schizophrenia is a disorder of cerebral disconnectivity whose lifetime course is
      modeled as both neurodevelopmental and neurodegenerative. The neurodevelopmental
      models attribute schizophrenia to alterations in the prenatal-to-early adolescent
      development. The neurodegenerative models identify progressive neurodegeneration
      as its core attribute. Historically, the physiology, pharmacology, and treatment
      targets in schizophrenia were conceptualized in terms of neurons,
      neurotransmitter levels, and synaptic receptors. Much of the evidence for both
      models was derived from studies of cortical and subcortical gray matter. We argue
      that the dynamics of the lifetime trajectory of white matter, and the consistency
      of connectivity deficits in schizophrenia, support white matter integrity as a
      promising phenotype to evaluate the competing evidence for and against
      neurodevelopmental and neurodegenerative heuristics. We develop this perspective
      by reviewing normal lifetime trajectories of white and gray matter changes. We
      highlighted the overlap between the age of peak of white matter development and
      the age of onset of schizophrenia and reviewed findings of white matter
      abnormalities prior to, at the onset, and at chronic stages of schizophrenia. We
      emphasized the findings of reduced white matter integrity at the onset and
      findings of accelerated decline in chronic stages, but the developmental
      trajectory that precedes the onset is largely unknown. We propose 4 probable
      lifetime white matter trajectory models that can be used as the basis for
      separation between the neurodevelopmental and neurodegenerative etiologies. We
      argue that a combination of the cross-sectional and longitudinal studies of white
      matter integrity in patients may be used to bridge the neurodevelopment and
      degeneration heuristics to advance schizophrenia research.

PMID- 24870448
TI  - Antitumor effects of a monoclonal antibody to human CCR9 in leukemia cell
      xenografts.
AB  - Tumor expression of certain chemokine receptors is associated with resistance to
      apoptosis, migration, invasiveness and metastasis. Because CCR9 chemokine
      receptor expression is very restricted in healthy tissue, whereas it is present
      in tumors of distinct origins including leukemias, melanomas, prostate and ovary
      carcinomas, it can be considered a suitable candidate for target-directed
      therapy. Here, we report the generation and characterization of 91R, a mouse anti
      human CCR9 IgG2b monoclonal antibody that recognizes an epitope within the CCR9 N
      terminal domain. This antibody inhibits the growth of subcutaneous xenografts
      from human acute T lymphoblastic leukemia MOLT-4 cells in immunodeficient Rag2(-/
      ) mice. Tumor size in 91R-treated mice was reduced by 85% compared with isotype
      matched antibody-treated controls. Tumor reduction in 91R-treated mice was
      concomitant with an increase in the apoptotic cell fraction and tumor necrotic
      areas, as well as a decrease in the fraction of proliferating cells and in tumor
      vascularization. In the presence of complement or murine natural killer cells,
      91R promoted in vitro lysis of MOLT-4 leukemia cells, indicating that this
      antibody might eliminate tumor cells via complement- and cell-dependent
      cytotoxicity. The results show the potential of the 91R monoclonal antibody as a
      therapeutic agent for treatment of CCR9-expressing tumors. 

PMID- 24870451
TI  - Scanning electron microscopy of scales and its taxonomic application in the fish
      genus Channa.
AB  - Scanning electron microscopy (SEM) of scales in six species of the fish genus
      Channa revealed certain features relevant to taxonomic significance. The location
      of focus, inter-radial distance and width of circuli, inter-circular space, width
      of radii, shape and size of lepidonts, etc. were found to be different in
      different species. The importance of SEM of scales in poorly understood taxonomy
      and phylogeny of the fish genus Channa is discussed with the help of relevant
      literature. Further, the role of SEM of fish scales for taxonomic applications is
      discussed in detail. 

PMID- 24870452
TI  - [Feedback on service provision in cancer patients using the Ward Satisfaction
      Questionnaire (WSQ)--testing a new tool].
AB  - BACKGROUND: Collecting information on patients' experiences and opinions is
      prerequisite to improving the quality of services at a ward. The Ward
      Satisfaction Questionnaire (WSQ) was developed for this purpose. We investigated
      its psychometric characteristics and percentage of missing values. METHODS: Over
      a period of 4 months, all patients at an interdisciplinary and an oncology ward
      were asked to complete the WSQ. Concordant validity was assessed using the
      Patient Involvement in Care Scales (PICS). RESULTS: 68 of 99 administered
      questionnaires were completed (response rate 69 %). The median of missing values
      per item was 6 % (0 -28 %). Internal consistency of the WSQ scales ranged from
      0.68 ("Accessibility of Doctors") to 0.94 ("Doctor Consultations"). Cronbach's
      Alpha of the total score was 0.94. Scaling errors were 0 % ("Ward Rounds",
      "Doctor Consulations", "Accessibility Nurses") to 17 % ("Accessibility Doctors").
      Variances of WSQ scales were relatively low. Correlation patterns of WSQ and PICS
      support the validity of WSQ. CONCLUSIONS: The WSQ facilitates systematic feedback
      on inpatient services. Psychometric characteristics are good and validation in a
      larger patient sample is warranted.

PMID- 24870450
TI  - Action imitation changes perceptual alternations in binocular rivalry.
AB  - Binocular rivalry is a visual phenomenon in which perception alternates between
      two different monocular images presented to each of the two eyes. Here, we
      propose using this phenomenon as a method to study the relation between action
      execution and action perception. In our experiment, a simple background (a
      checkerboard) was contrasted with a video representing a hand continuously
      grasping and releasing a ball. In Experiment 1, our subjects were asked to
      reproduce the perceived movement with their right hand whenever they became aware
      of it and to stop doing this when the checkerboard dominated. Our results
      revealed that motor imitation of the perceived action significantly increased the
      time spent perceiving the hand. Three control experiments showed that these
      effects were not due to a generic involvement of focused attention (Experiment 2
      and 3), to a verbal description of the performed action (Experiment 3) or to the
      execution of an unrelated movement of the hand (Experiment 4). Although an
      intrinsic connection between action execution and attention cannot be excluded
      with certainty, and the boundary between action imitation and unrelated action
      execution may vary along various degrees of similarity, on the whole, the present
      results seem to suggest, at least on a preliminary basis, that action imitation
      do play a relevant role in the perception of action. We discuss these findings in
      the frame of current theories concerning the relation between perception and
      action. 

PMID- 24870453
TI  - Additional records and descriptions of the ant-mimetic plant bug genus Pilophorus
      from Thailand (Hemiptera: Heteroptera: Miridae: Phylinae: Pilophorini).
AB  - Eleven species of the ant-mimetic plant bug genus Pilophorus Hahn from Thailand
      are documented, with photographic images of live individuals. Four new species
      with conventional, moderate antlike shape, Pilophorus meteorus, P. saovapruki, P.
      subparallelus and P. suwimonae, are described. Two known Thai species, P. alstoni
      Schuh and P. typicus (Distant), are further reported and diagnosed. Biological
      information including host association is provided for P. alstoni, P. meteorus,
      P. saovapruki and P. typicus. A checklist of all currently known species of
      Pilophorus in Thailand and a key to known Thai species are included. Pilophorus
      typicus is reported from Singapore for the first time. 

PMID- 24870454
TI  - A new genus and species of Cyproideidae (Crustacea: Peracarida: Amphipoda) from a
      tropical coral reef, SE Gulf of Mexico.
AB  - Sisalia carricarti new genus, new species, is described on specimens collected
      from the Sisal Coral Reef System, Southern Gulf of Mexico, Mexico. The new genus
      is most morphologically similar to the genus Paracyproidea, but can be
      distinguished by the article 2 of antenna 2 peduncle, the peduncle of the uropods
      and length of rami, and telson. Also, the new genus can be distinguished from the
      rest 18 genera of the family Cyproideidae by the following characteristics: 3
      articulate mandible palp, mandible molar big and triturative; palp on maxilla 2
      uniarticulate; article 2 of pereopods 3-7 rectilinear, and urosomites 1-3 not
      elongated. Sisalia carricarti new genus, new species, represents the second known
      genus and third species of cyproideid amphipods documented from the Inter
      American Sea (Gulf of Mexico and Caribbean Sea), and the 19th genus and 44th
      species of the world cyproideid fauna. The more significant morphological
      characters and the geographical distribution of the 19 known genera of cyproideid
      amphipods are also pointed out. 

PMID- 24870455
TI  - Taxonomic revision of Australian Platynectes Regimbart, 1879 (Part I)-four new
      species from Queensland (Coleoptera: Dytiscidae, Agabinae).
AB  - Four species of the genus Platynectes subgenus Gueorguievtes Vazirani, 1976 are
      described from Queensland, Australia: Platynectes brancuccii sp. n. (Atherton
      Tableland), P. larsoni sp. n. (Mulgrave Range and Windsor Tableland), P. ponderi
      sp. n. (Carnarvon Range) and Platynectes weiri sp. n. (White Mountains National
      Park and Hope Vale Mission). The latter two are the first species of the genus
      with striae on elytra and the informal P. weiri-species group is established for
      them. Platynectes brancuccii sp. n. and P. larsoni sp. n. belong to the P.
      decempunctatus-species group. All four species were collected from small rain
      forest streams or rest pools of intermittent creeks. Important species characters
      (median lobes, parameres and colour patterns) of all species are figured, and
      notes on their distribution and ecology are given. Altogether 17 species of the
      genus are now known from Australia. 

PMID- 24870456
TI  - Two new species of the genus Okinawepipona Yamane (Hymenoptera: Vespidae:
      Eumeninae) from Vietnam and China.
AB  - Two new species are described and figured: Okinawepipona nigra Nguyen & Xu, sp.
      nov. (northern Vietnam and southern China), and O. curcipunctura Nguyen & Xu, sp.
      nov. (southern China). A key to the three known species of the genus is provided.

PMID- 24870457
TI  - A new species of lizard in the genus Caledoniscincus (Reptilia: Scincidae) from
      far northwest New Caledonia.
AB  - A new species of skink in the genus Caledoniscincus is described from the far
      north-west region of New Caledonia. It is known from a single location, the
      isolated ultramafic massif of Dome de Tiebaghi, north of Koumac. The new species,
      Caledoniscincus pelletieri sp. nov., has a bold, white mid-lateral stripe on the
      body, a feature which distinguishes it from most other species of Caledoniscincus
      except the regionally sympatric Caledoniscincus haplorhinus (Gunther) and
      Caledoniscincus austrocaledonicus (Bavay), and the recently described
      Caledoniscincus constellatus Sadlier, Whitaker, Wood & Bauer just to the south.
      The new species can be distinguished from these taxa in features of scalation and
      colouration, most notably in lacking an extension of the pale midlateral stripe
      between the ear and forelimbs and in having more lamellae on the underside of the
      fourth toe. The differences in morphology between C. pelletieri sp. nov. and the
      other members of the genus are complemented by a high level of genetic
      differentiation, further supporting its distinctiveness as an independent
      evolutionary lineage warranting recognition as a distinct species. The DNA
      sequence data for the ND2 mitochondrial gene identifies the new species as the
      sister to C. constellatus and these two taxa as the sister to all
      Caledoniscincus. The species is of extremely high conservation concern given its
      restricted distribution in an area that is currently being heavily impacted by
      human activities, and it satisfies the IUCN criteria to be ranked as a Critically
      Endangered species. 

PMID- 24870458
TI  - New species of salamander (Caudata: Plethodontidae: Cryptotriton) from Quebrada
      Cataguana, Francisco Morazan, Honduras, with comments on the taxonomic status of
      Cryptotriton wakei.
AB  - We describe a new species of the plethodontid salamander genus Cryptotriton from
      Honduras after comparing morphological, molecular, and osteological data from the
      holotype to that of the other nominal forms of the genus. The new species differs
      from all of the known species of Cryptotriton in at least one character from all
      three datasets. We also suggest placing C. wakei in the synonymy of C. nasalis
      after examining the morphological and osteological characters of the single known
      specimen of C. wakei. 

PMID- 24870459
TI  - A new species of Magneuptychia Forster, 1964 (Lepidoptera: Nymphalidae:
      Satyrinae) from Brazilian Savanna.
AB  - A new species of Satyrinae butterfly from the Brazilian Savanna, Magneuptychia
      flavofascia n. sp., is described based on adult morphological characters with a
      discussion about its placement within the genus. 

PMID- 24870460
TI  - The Poaceae-associated genus Bamboosiella (Thysanoptera, Phlaeothripidae) from
      India with one new species.
AB  - Bamboosiella venkataramani sp. n. is described from India based on specimens
      collected on grass clumps from the Karnataka State of India. A key is provided
      for identification of seven Indian species of the genus Bamboosiella. 

PMID- 24870461
TI  - A new species of the genus Linoderus Sharp, 1885 (Coleoptera, Staphylinidae,
      Philonthina) from the Colombian Andes.
AB  - The monotypic genus Linoderus Sharp, 1885 was described based on a species from
      Panama and since the original description nearly nothing has been added to its
      taxonomical knowledge. The aim of the present paper is to describe a new species
      of the genus from Colombia and to report the genus for the first time from South
      America, adding some biological notes of the species. 

PMID- 24870462
TI  - A new genus and species of phytoseiid mite (Acari: phytoseiidae) from the
      Brazilian Atlantic Forest.
AB  - A new genus, Ingaseius nov. gen., and a new species, Ingaseius silvaticus nov.
      sp., Phytoseiidae, collected from Inga edulis Martius and Inga marginata Wild.
      (Fabaceae) are described from the Brazilian Atlantic Forest. This species is
      unique in the following characteristics: females and males with few teeth on
      fixed cheliceral digit and short Jv5, without J2, Z1 and leg macrosetae. In
      addition, females lack Jv3 and Zv3, and have a reduced ventrianal shield.  

PMID- 24870463
TI  - Correct authorship of the genus Pyrgilauda (Aves: Passeridae).

PMID- 24870464
TI  - The correct stems of family-group names citing Ortalis Merrem, 1786, as type
      genus (Aves: Cracidae).

PMID- 24870465
TI  - Gryporhynchidae (Cestoda: Cyclophyllidea) in Mexico: species list, hosts,
      distribution and new records.
AB  - As a result of this study, 8 new host (Botaurus lentiginosus for Glossocercus
      caribaensis and Valipora mutabilis; Egretta caerulea for Valipora minuta; Egretta
      thula for Glossocercus cyprinodontis; Egretta tricolor and Nycticorax nycticorax
      for Glossocercus caribaensis; Pelecanus occidentalis and Platalea ajaja for
      Paradilepis caballeroi) and 31 new locality records for gryporhynchid cestode
      species in Mexico are presented. With these data, the total number of species of
      this group of helminths in Mexico becomes 25 (19 named species and 6 unidentified
      taxa), which have been registered as parasites of fishes (47 host species) and
      (or) birds (20 host species). This information comes from 102 localities,
      pertaining to 20 of 32 Mexican states. Five of the 25 taxa have been exclusivelly
      collected in fishes, 7 in fish-eating birds, and 13 in both groups of hosts. The
      most frequent metacestodes found in Mexican fishes are the merocercoids of
      Cyclustera ralli, Valipora mutabilis, Parvitaenia cochlearii and Valipora
      campylancristrota; in adult stage, Glossocercus caribaensis was the species with
      the largest host spectrum, while Paradilepis caballeroi has the widest
      distribution range. The work includes parasite/host lists, as well as habitat,
      distribution, references and information on specimens' deposition. 

PMID- 24870466
TI  - New species and records of Trypetinae (Diptera: Tephritidae) from India.
AB  - Two new species of the subfamily Trypetinae, Acidoxantha galibeedu David &
      Ramani, sp. nov. (tribe Nitrariomyiini) and Philophylla lachung Singh & David,
      sp. nov. (tribe Trypetini) are described from India. Acidoxantha totoflava is
      documented as new record from India. Keys to the species of known Acidoxantha
      Hendel and Indian Philophylla Rondani are provided. 

PMID- 24870467
TI  - New species of Bryozoa from Madeira associated with rhodoliths.
AB  - Four new species of cheilostomate Bryozoa encrusting rhodoliths on Maerl beds are
      described from material collected at a single locality at Madeira Island. These
      are Coronellina atlantica n. sp., Hippothoa muripinnata n. sp., Chorizopora
      rosaria n. sp. and Hippoporella maderensis n. sp. A species of Schizomavella is
      left in open nomenclature. The genus Coronellina is transferred from the family
      Calescharidae and assigned to Microporidae. The close similarity of C. atlantica
      n. sp., a non-opesiulate species with deep depressions, to Coronellina fagei with
      opesiules, implies that the generally accepted evolutionary sequence from non
      opesiulate to opesiulate species might not be the rule. 

PMID- 24870468
TI  - An updated key to the species of Fannia Robineau-Desvoidy (Diptera: Fanniidae) of
      southern South America, and the description of a new species from Mendoza,
      Argentina.
AB  - The aim of this study is to describe Fannia puxcu sp. n., a new species of the
      genus Fannia Robineau-Desvoidy (Diptera: Fanniidae) that was collected in the
      Villavicencio Provincial Reserve in Mendoza, Argentina, and to present an updated
      key to the 27 species of Fannia Robineau-Desvoidy (Diptera: Fanniidae) of
      Southern South America. The male of F. puxcu sp. n. is described, and
      illustrations provided as well as distributional records and a discussion of its
      possible phylogenetic affinities. 

PMID- 24870469
TI  - Belesica madiba and Cremastus tutui (Ichneumonidae: Cremastinae), two
      entomological gems from South Africa.
AB  - The Afrotropical cremastine fauna (Hymenoptera: Ichneumonidae) is characterized
      by the near absence of the genus Cremastus, with a single species reported from
      Madagascar. The fauna is also characterized by the presence of several endemic
      genera. Among the latter is the exceptional monotypic genus Belesica. We describe
      two new species from these extremely rare Afrotropical genera, namely Belesica
      madiba sp. nov. and Cremastus tutui sp. nov.. Both are only known from South
      Africa. 

PMID- 24870470
TI  - Review of the Oriental genus Neunkanodes Yang (Hemiptera: Fulgoromorpha:
      Delphacidae) with descriptions of two new species.
AB  - The Oriental planthopper genus Neunkanodes Yang, 1989 (Hemiptera: Fulgoromorpha:
      Delphacidae: Delphacinae: Delphacini) is reviewed to include three species: N.
      bispinatus sp. nov. (China: Yunnan), N. formosana Yang, 1989 (China: Taiwan,
      Guizhou, Yunnan) and N. unispinatus sp. nov. (China: Yunnan). The generic
      characteristics are redefined. The main morphological characters and male
      genitalia of three species are described or redescribed and illustrated. A key to
      the known species in the genus is provided. 

PMID- 24870471
TI  - Onychogomphus marijanmatoki, a new species from Sarawak, Borneo (Odonata:
      Anisoptera: Gomphidae).
AB  - Onychogomphus marijanmatoki is described from a male from Gunung Mulu National
      Park, Miri Division, Sarawak, Malaysian Borneo. One of only two onychogomphine
      species known from Borneo, it differs from all others of the group in characters
      of the genital ligula and terminal appendages. 

PMID- 24870472
TI  - Two new species of Chelifera Macquart from China (Diptera: Empididae).
AB  - Two new Chelifera species, C. liuae sp. nov. from Sichuan and C. tibetensis sp.
      nov. from Tibet, are described. The genus Chelifera is recorded from Tibet for
      the first time. Cheliefera tibetensis is assigned to the C. rhombicercus-group.
      An updated key to the species of Chelifera from China is provided. 

PMID- 24870473
TI  - First record of Poemeniinae (Hymenoptera, Ichneumonidae) from Peru, with
      description of a new species and a key to the world species of Ganodes Townes.
AB  - The subfamily Poemeniinae (Hymenoptera, Ichneumonidae) is reported for the first
      time from Peru. We describe and illustrate a new species, Ganodes atayupanquii
      sp. n. Castillo & Saaksjarvi, which was collected from the Peruvian Andes at 1500
      m. A key to the species of Ganodes Townes and new distribution records of G.
      wahli Diaz and G. matai Gauld are provided. 

PMID- 24870474
TI  - A lectotype for Cyathophora richardi Michelin 1843.
AB  - The figured syntype of Cyathophora richardi Michelin 1843, type species of the
      genus Cyathophora Michelin 1843, was recovered from the collection of the Museum
      national d'Histoire naturelle (MNHN, Paris, France). It is herein designated as a
      lectotype in order to keep the traditional usage of the widely used genus
      Cyathophora.

PMID- 24870475
TI  - Revision of the African horntail genus Afrotremex (Hymenoptera: Siricidae).
AB  - Afrotremex is one of ten extant genera of Siricidae, known as horntails or
      woodwasps. Species are restricted to the central forested regions of Africa.
      Their biology and economic significance are unknown. However, the host of one
      species, A. xylophagus, is known. Their larvae are wood-boring insects. The genus
      consists of six species: Afrotremex hyalinatus (Mocsary), A. violaceus Pasteels,
      A. comatus Goulet, n. sp., A. opacus Goulet, n. sp., A. pallipennis Goulet, n.
      sp., and A. xylophagus Goulet, n. sp. The genus is characterized, its
      phylogenetic placement is discussed, and a key to species is provided. For each
      species (if pertinent), the following are included: synonymy, diagnosis,
      comparative diagnosis, description, type material, origin of specific epithet,
      taxonomic notes, and range. 

PMID- 24870476
TI  - New Neotropical Culicoides and redescription of Culicoides reticulatus Lutz
      (Diptera: Ceratopogonidae).
AB  - Seven new species of the Culicoides reticulatus species group are described and
      illustrated based on specimens from Colombia, Panama and Brazilian states of
      northern (Amazonas, Para and Roraima) and southeast region (Rio de Janeiro). The
      new species are compared with their similar congener, Culicoides reticulatus
      Lutz, and a systematic key, table with numerical characters to the females of the
      species are provided. Redescription of Culicoides reticulatus Lutz is given based
      on type series deposited in the Ceratopogonidae Collection of the Oswaldo Cruz
      Foundation, Brazil. The distribution of these species is presented in figure 9. 

PMID- 24870477
TI  - The spider genera Euthycaelus Simon and Schismatothele Karsch (Mygalomorphae,
      Theraphosidae).
AB  - The genus Euthycaelus Simon 1889 is diagnosed based on the examination of type
      material and additional material from Venezuela and Colombia. The genus now
      includes: Euthycaelus colonicus Simon 1889, E. norae sp. nov., E. amandae sp.
      nov.; Euthycaelus steini Simon 1889 is transferred to Psalistops comb. nov. The
      genus Schismatothele Karsch 1879 is considered a senior synonym of Hemiercus
      Simon 1903. Schismatothele includes S. lineata Karsch 1879, S. inflata (Simon
      1889) comb. nov., S. modesta (Simon 1889) comb. nov, and S. benedettii Panzera et
      al. 2011. Hemiercus proximus Mello-Leitao 1923, from Cubatao, Sao Paulo, Brazil,
      is transferred to Acanthoscurria proxima (Mello-Leitao 1923) comb. nov. Hemiercus
      kastoni Caporiacco 1955 is considered a species inquirenda pending the
      examination of the type material. 

PMID- 24870478
TI  - Identity of Baker's species described in the Oriental leafhopper genus Pythamus
      (Hemiptera: Cicadellidae) with description of a new genus.
AB  - Baker's (1915) species described in the Oriental leafhopper genus Pythamus
      Melichar are revised. One species, Pythamus melichari Baker 1915, is placed in a
      new genus, Pythochandra Wei & Webb, gen. n.. The four varieties of P. melichari
      described by Baker (1915, 1923) (borneensis, bilobatus, decoratus and
      singaporensis) are elevated to species level and placed in the new genus stat.
      n., comb. n.. All species are briefly described and a key is provided for their
      separation. Two other species, Pythamus productus Baker and P. decoratus Baker,
      known only from females, are retained in Pythamus pending further studies. 

PMID- 24870479
TI  - Review of the genus Tachytes Panzer (Hymenoptera: Crabronidae: Crabroninae) of
      South Korea, with description of one new species.
AB  - Korean species of the genus Tachytes Panzer are reviewed. Four previously known
      species are confirmed, and one new species, Tachytes gyusanus is described. The
      new species is very similar to T. modestus, but it differs critically in the form
      of male genitalic capsule. A revised key to South Korean species, a description
      of the new species, and digital images and line drawings of diagnostic
      characteristics are provided. 

PMID- 24870480
TI  - Taxonomic reassessment of Blanus strauchi (Bedriaga, 1884) (Squamata:
      Amphisbaenia: Blanidae), with the description of a new species from southeast
      Anatolia (Turkey).
AB  - The study of mitochondrial and nuclear DNA sequences reveals that the polytypic
      Blanus strauchi is a species complex including three well-defined allopatric
      clades, one of which consists of two sub-clades. Only the two sub-clades of the
      Western clade are morphologically diagnosable in the field, whereas obvious
      characters to distinguish the Central and the Eastern clades are lacking.
      However, all four clades show significant statistical differentiation on meristic
      traits, as well as in morphometric characters of the head when compared by means
      of the geometric morphometrics. The genetic distance between the three major
      mitochondrial clades is comparable to the p-distances for the same markers
      observed between Blanus species-pairs from Morocco and the Iberian Peninsula,
      respectively. The nuclear marker confirms the mitochondrial clades, and shows
      that the three major clades do not share any haplotypes, as an indication of
      restricted gene flow among them. On the basis of this evidence, the taxonomy of
      Blanus strauchi is re-assessed: the Western clade corresponds to B. strauchi,
      with two subspecies: B. s. strauchi and B. s. bedriagae. The Central clade
      corresponds to B. aporus, here elevated at the species rank. For the eastern
      clade there are no available names, and therefore it is described here as Blanus
      alexandri sp. nov. 

PMID- 24870481
TI  - New taxa and taxonomic revisions to the Poraniidae (Valvatacea; Asteroidea) with
      comments on feeding biology.
AB  - New molecular phylogenetic data and new specimens provide the basis for a
      revision of the family Poraniidae. We present molecular phylogenetic data for
      five out of 11 genera in the Poraniidae including a newly discovered taxon from
      the North Pacific. Bathyporania ascendens nov. gen., nov. sp., is described from
      Davidson Seamount (35o43'N, 122o43'W). Another newly discovered poraniid taxon,
      Clavaporania fitchorum nov. gen., nov. sp. is described from south of Macquarie
      Island (56o21'S, 158o 28'E) but was not included in the analysis. Revision of the
      Poraniidae has been undertaken. We present two new genera and reinstate the
      previously synonymized genus Glabraster and return Culcitopsis to genus level.
      The genus Porania sensu Clark (1993) and Clark and Downey (1992) is not
      monophyletic. Porania, Poraniomorpha and Poraniopsis are revised. In situ feeding
      observations of Bathyporania are described and compared with other poraniid
      feeding accounts. 

PMID- 24870482
TI  - A new species of Centruroides Marx (Scorpiones: Buthidae) from Panama and new
      distribution records for Centruroides bicolor (Pocock, 1898) and Centruroides
      granosus (Thorell, 1876).
AB  - A new species, Centruroides panamensis n. sp., from the foothills of Volcan Baru
      in the Province of Chiriqui, Panama is described with a extremely narrow
      distributional range. New distribution records of Centruroides bicolor (Pocock,
      1898) are also presented. 

PMID- 24870483
TI  - Review of Europiella Reuter (Hemiptera: Heteroptera: Miridae: Phylinae: Phylini)
      from Korea, with a description of a new genus.
AB  - Five species of Europiella (Phylinae: Phylini) including three newly reported
      species, E. artemisiae (Becker, 1864), E. kiritshenkoi Kulik, 1975, and E.
      miyamotoi (Kerzhner, 1988), are recognized for the first time from Korea, and
      Europiella albipennis (Fallen, 1829) is removed from the Korean list. A new genus
      Europiellomorpha Duwal n. gen., is proposed to accommodate Plagioganthus
      lividellus (Kerzhner, 1979) (= Europiella lividellus). A key to the Korean
      species of Europiella, diagnosis, and descriptions of both male and female
      genitalia are provided. 

PMID- 24870484
TI  - A new species of the hippolytid shrimp genus Thor Kingsley, 1878 (Crustacea:
      Decapoda: Caridea) from Hainan Island, China.
AB  - A new species of the caridean family Hippolytidae, Thor hainanensis sp. nov., is
      described and illustrated based on specimens from Hainan Island, China. The
      carpus of the second pereopod is six-segmented; the mandible has only the incisor
      process and the molar process; the third segment of antennular peduncle has one
      subtriangular dorsal scale. Those morphological characters easily classify this
      species into the genus Thor Kingsley, 1878. First pereopod with epipod
      distinguishes the present new species from the other members of the genus,
      because the existence of epipod among different pereopods is considered to be
      fixed at interspecific level and all the described species of this genus lack the
      epipod on the first pereopod. 

PMID- 24870485
TI  - A new subgenus and three new species of oribatid mites of the genus Yoshiobodes
      (Acari, Oribatida, Carabodidae) from Vietnam.
AB  - A new subgenus and three new species of oribatid mites of the genus Yoshiobodes,
      Yoshiobodes (Dongnaiobodes) subgen. nov., Y. (D.) hexasetosus sp. nov., Y. (D.)
      biconcavus sp. nov. and Y. (Yoshiobodes) neotrichorostralis sp. nov., are
      described from southern Vietnam. Yoshiobodes (Dongnaiobodes) subgen. nov. differs
      from the other subgenera, Yoshiobodes (Yoshiobodes) and Yoshiobodes
      (Berndobodes), by the presence of five to six pairs of genital setae (versus
      four). Yoshiobodes (D.) hexasetosus sp. nov. differs from Yoshiobodes (D.)
      biconcavus sp. nov. by the absence of two large concavities in humeral regions of
      the notogaster and the presence of short, clavate sensilli (versus concavities
      well developed, sensilli long, thickened, setiform). Yoshiobodes (Y.)
      neotrichorostralis sp. nov. differs from the other species of the subgenus by the
      presence of three additional pairs of setae on the lateral sides of the rostrum
      and the foveolate ornamentation on the notogaster (versus additional setae
      absent, surface tuberculate). The new generic diagnosis and an identification key
      to all known species of Yoshiobodes are given. Yoshiobodes ornatus Mahunka, 1987
      is proposed as "nomen nudum". Austrocarabodes (Austrocarabodes) polytrichus
      Balogh & Mahunka, 1978 combined in the subgenus Austrocarabodes (Uluguroides): A.
      (U.) polytrichus comb. nov.. 

PMID- 24870486
TI  - Phylogenetic affinities of Monarea Szepligeti, 1904 (Hymenoptera: Braconidae,
      Doryctinae, with description of a new species from Mexico.
AB  - The genus Monarea Szepligeti is recorded from Mexico for the first time. A new
      species, Monarea fridae sp. nov., is described and illustrated from the states of
      Morelos, Puebla and Jalisco, Mexico. The phylogenetic placement of the genus is
      investigated based on nuclear (28S) and mitochondrial (COI) DNA sequence data.
      Based on the relationships recovered, Monarea is transferred to the tribe
      Holcobraconini, which is also supported by features of the internal ovipositor
      structure and the venom glands and reservoir. A key to the four currently
      recognised species of Monarea is provided. 

PMID- 24870487
TI  - Description of Trichodorus iranicus sp. n. (Diphtherophorina, Trichodoridae) from
      Iran.
AB  - Trichodorus iranicus sp. n. is described and illustrated based on morphological
      and molecular characters and morphometric data. It belongs to the T. lusitanicus
      morphospecies group based on the shape of the spicules and vaginal sclerotised
      pieces. Males have a body length of 844-942 um, onchiostyle length of 59 um,
      three cervical papillae (CP), curved spicules, 28-30 um in length, with narrow
      mid-part, sometimes provided with a few bristles, and slightly developed
      manubrium. Females of the new species are 727-870 um long with secretory
      excretory pore located opposite anterior end of pharyngeal bulb, vagina length 46
      57% of corresponding body width, with triangular to triangular-rounded
      sclerotised pieces 3.5 um long, 1-2 um apart from each other, and vulva a
      transverse slit. In its morphology, the new species resembles T. andalusicus, T.
      asturanus, T. azorensis, T. beirensis, T. lusitanicus, T. velatus and T.
      viruliferus and the morphological and morphometric differences separating T.
      iranicus from these known species are discussed. The D2-D3 region of 28S rDNA for
      the new species was amplified and the 679 bp newly-obtained sequence was used in
      a Bayesian inference (BI) analysis which confirmed the close relationship of the
      new species with T. lusitanicus morphospecies group members and placed it as a
      sister taxon to T. andalusicus in a well-supported clade that also includes T.
      asturanus. 

PMID- 24870489
TI  - Description of two new species of the genus Megophrys (Amphibia: Anura:
      Megophryidae) from Heishiding Nature Reserve, Fengkai, Guangdong, China, based on
      molecular and morphological data.
AB  - Two new species, Megophrys acuta sp. nov. and Megophrys obesa sp. nov., are
      described based on a series of specimens collected from Heishiding Nature
      Reserve, Fengkai County, Guangdong Province, China. They can be distinguished
      from other known congeners occurred in southern and eastern China by
      morphological characters and molecular divergence in the mitochondrial 16S rRNA
      gene. M. acuta is characterized by small and slender body with adult females
      measuring 28.1-33.6 mm and adult males measuring 27.1-33.0 mm in snout-vent
      length; snout pointed, strongly protruding well beyond margin of lower jaw;
      canthus rostralis well developed and sharp; hindlimbs short, the heels not
      meeting, tibio-tarsal articulation reaching forward the pupil of eye. M. obesa is
      characterized by stout and slightly small body with adult females measuring 37.5
      41.2 mm, adult male measuring 35.6 mm in snout-vent length; snout round in dorsal
      view; canthus rostralis developed; hindlimbs short, the heels not meeting, tibio
      tarsal articulation reaching forward the posterior margin of eye. The discovery
      of these two new species further confirms that the diversity of this genus has
      been significantly underestimated. At present the genus Megophrys contains 56
      species of which 35 species are distributed in China. 

PMID- 24870488
TI  - A new species of Miroculis Edmunds, 1963 (Ephemeroptera: Leptophlebiidae) from
      northeastern Brazil.
AB  - Miroculis stenopterus, sp. nov., is described based on material from State of
      Pernambuco, Northeastern Brazil. The imago of the new species can be
      distinguished, among other characteristics, by an uncommon forewing shape, long
      and narrow, similar to species of genus Microphlebia. The tentatively associated
      nymph can be distinguished from other species of the genus mainly by the
      abdominal color pattern and the ratio of labial palp segment 2 to segment 1 (1.01
      1.04 x). 

PMID- 24870491
TI  - Additional dates of Sir Andrew Smith's Illustrations of the Zoology of South
      Africa.
AB  - We update the collation of the dates of publication of Smith's Illustrations of
      the Zoology of South Africa provided by Waterhouse (1880) and Barnard (1950,
      1952). In the case of nine parts, we are able to provide more accurate dates of
      publication (including day-dates for seven of these parts). For workers of
      invertebrate taxonomy, we provide an accurate date of publication for W. S.
      Macleay's volume on Annulosa.  

PMID- 24870490
TI  - A new genus of Conopidae from Europe (Diptera).
AB  - The monotypic genus Merziella gen. nov. (Palaearctic Region: Europe) is
      described. A key to the genera of the subfamily Myopinae is presented. 

PMID- 24870493
TI  - First record of Megacydnus secundus J. A. Lis, 2002, a representative of
      Afrotropical endemic burrower bug genus from Uganda, and an annotated checklist
      of Ugandan Cydnidae (Hemiptera: Heteroptera).
AB  - The Cydnidae (Hemiptera: Heteroptera: Pentatomoidea) is a true bug family with
      almost 700 species distributed worldwide (Lis 1996, 1999, 2006). These bugs
      usually dig in the ground (e.g., sand, soil, litter) and, therefore, are commonly
      known as the burrower bugs or burrowing bugs. Digging in the ground is possible
      because of several morphological adaptations, including well-developed tibial
      combs (Lis and Schaefer 2005), coxal combs (Lis 2010), and strong hair-like and
      peg-like setae on the head margins in larval and adult stages (Lis and Pluot
      Sigwalt 2002) (see: Fig. 1A). 

PMID- 24870492
TI  - Aeshna shennong sp. nov., a new species from Hubei Province, China (Odonata:
      Anisoptera: Aeshnidae).
AB  - Aeshna shennnong sp. nov. (holotype male: Dajiuhu national wetland park in
      Shennongjia National Nature Reserve, Shennongjia City, Hubei Province, China, 28.
      VIII. 2013) is described, illustrated and compared with its most similar
      congener, A. petalura Martin, 1908. The holotype will be deposited in the
      Collection of Aquatic Animals, Institute of Hydrobiology, Chinese Academy of
      Sciences, Wuhan City, Hubei Province, China. New distribution records of A.
      petalura from mainland China are also provided. 

PMID- 24870494
TI  - The dating of the ornithological section of Middendorff's Reise in den aussersten
      Norden und Osten Sibiriens, with comments on the nomenclature of Pallas's Bunting
      Emberiza pallasi Cabanis (Aves: Emberizidae).
AB  - Middendorff's work on the Saugethiere, Vogel und Amphibien, published as part 2
      of volume 2 of his Reise in den aussersten Norden und Osten Sibiriens, was
      variably dated from 1851, 1852 or 1853. I document that the work was published
      shortly before 15 December 1852 and I recommend using this date for the purposes
      of zoological nomenclature.Due to this, Emberiza polaris Middendorff, 1852 has
      precedence over Cynchramus pallasi Cabanis, 1853. This bunting species thus
      should be called Emberiza polaris and its four subspecies should be called
      Emberiza polaris polaris Middendorff, 1852, E. polaris minor Middendorff, 1852,
      E. polaris pallasi (Cabanis, 1853) and E. polaris lydiae Portenko, 1929.  

PMID- 24870495
TI  - Disentangling the Pelomedusa complex using type specimens and historical DNA
      (Testudines: Pelomedusidae).
AB  - Recent research has shown that the helmeted terrapin (Pelomedusa subrufa), a
      species that occurs throughout sub-Saharan Africa, in Madagascar and the
      southwestern Arabian Peninsula, consists of several deeply divergent genetic
      lineages. Here we examine all nominal taxa currently synonymized with Pelomedusa
      subrufa (Bonnaterre, 1789) and provide mitochondrial DNA sequences of type
      specimens or topotypic material for most taxa. Lectotypes are designated for
      Testudo galeata Schoepff, 1792, Pentonyx capensis Dumeril & Bibron, 1835,
      Pelomedusa nigra Gray, 1863, Pelomedusa galeata var. disjuncta Vaillant &
      Grandidier, 1910, and Pelomedusa galeata damarensis Hewitt, 1935. For Pelomedusa
      gasconi Rochebrune, 1884, a taxon without preserved type material, a neotype is
      designated. Type material of Pentonix americana Cornalia, 1849, a nominal species
      without credible type locality, is lost and its identity remains questionable.
      Also the holotype of Pelomedusa galeata orangensis Hewitt, 1935 is lost, but its
      allocation to the only genetic lineage occurring in South Africa is unambiguous.
      Phylogenetic analyses of type sequences or topotypic material reveal that the
      remaining nominal taxa represent three of the nine previously identified lineages
      of Pelomedusa. Among these three lineages is the South African one. Type
      specimens of Pentonyx gehafie Ruppell, 1835 correspond to an additional distinct
      lineage. The present study provides a sound basis for a subsequent integrative
      taxonomic revision of the Pelomedusa complex. 

PMID- 24870496
TI  - A revision of African helmeted terrapins (Testudines: Pelomedusidae: Pelomedusa),
      with descriptions of six new species.
AB  - Using nearly range-wide sampling, we analyze up to 1848 bp of mitochondrial DNA
      of 183 helmeted terrapins and identify a minimum of 12 deeply divergent species
      level clades. Uncorrected p distances of these clades equal or clearly exceed
      those between the currently recognized species of Pelusios, the genus most
      closely related to Pelomedusa. We correlate genetic discontinuities of Pelomedusa
      with data on morphology and endoparasites and describe six new Pelomedusa
      species. Moreover, we restrict the name Pelomedusa subrufa (Bonnaterre, 1789) to
      one genetic lineage and resurrect three further species from its synonymy, namely
      P. galeata (Schoepff, 1792), P. gehafie (Ruppell, 1835), and P. olivacea
      (Schweigger, 1812). In addition to these ten Pelomedusa species, we identify two
      further clades from Cameroon and Sudan with similar levels of genetic divergence
      that remain unnamed candidate species. We also note that some problematical
      terrapins from South Africa and Somalia may represent two additional candidate
      species. Some of the Pelomedusa species are morphologically distinctive, whilst
      others can only be identified by molecular markers and are therefore
      morphologically cryptic taxa. 

PMID- 24870497
TI  - A new species of Carnoya Gilson, 1898 (Rhigonematida: Carnoyidae) parasite of a
      spirobolid (Diplopoda: Spirobolida) from Cuba.
AB  - Carnoya isabelica n. sp. is described parasitizing Nesobolus piedra from Eastern
      Cuba. The new species is characterized by the presence of 13 copulatory papillae
      in males (the post-cloacal arranged in two trios, with two lateral papillae and
      one median papilla that can be laterally displaced), the presence of collars of
      spines in the both sexes and females with 23-25 collars of spines, cephalic end
      not swollen and lateral alae extending from the end of spines to the base of the
      tail. SEM images of both sexes are given. 

PMID- 24870498
TI  - Giesbertiolus curoei, a new species of flower chafer from Panama with
      transitional characters (Coleoptera: Scarabaeidae: Cetoniinae: Trichiini).
AB  - Giesbertiolus curoei, new species is described from a female specimen collected
      in northwestern Panama. This species is compared with the three known species of
      Giesbertiolus Howden and with the genus Dialithus Parry. The genera Dialithus and
      Giesbertiolus are redefined to include this new species, and new diagnostic
      characters are provided for both. Illustrations of diagnostic characters and an
      identification key for the species of Giesbertiolus are provided. 

PMID- 24870499
TI  - Flexitibia, a new genus of Harpactorinae (Hemiptera: Heteroptera: Reduviidae),
      with a discussion on the functional morphology of forelegs of the related genera.
AB  - Flexitibia, a new genus, in the division Euagorasaria of the assassin bug
      subfamily Harpactorinae from Yunnan Province of China is described. The type
      species, Flexitibia orientalis sp. nov., is described and illustrated. A key to
      the closely related genera is provided. The type specimens are kept in the
      Entomological Museum of China Agricultural University, Beijing. 

PMID- 24870500
TI  - Phytoseiidae database: a website for taxonomic and distributional information on
      phytoseiid mites (Acari).
AB  - This paper announces a database on the taxonomy and distribution of mites of the
      family Phytoseiidae Berlese, which is available online at
      http://www.lea.esalq.usp.br/phytoseiidae/. Synthesis of species diversity per
      genus, subfamily and country are given. Information about use of the database is
      provided. 

PMID- 24870501
TI  - A new genus, Neoschidium (Hemiptera: Reduviidae: Emesinae), with a redescription
      of the type genus, Neoschidium phasma (Distant) [Ghilianella phasma Distant and
      Schidium phasma (Distant)], recorded for the first time from India.
AB  - A new genus, Neoschidium was erected with the type genus, Neoschidium phasma
      (Distant). It was earlier described under Ghilianella Spinola 1850 as G. phasma
      Distant and later under Schidium Bergroth 1916 as Schidium phasma (Distant) by
      Bergroth (1916). Because it exhibits characters not only of Ghilianella and
      Schidium but also intermediate specific characters that are not found in both the
      genera, the type genus Neoschidium phasma (Distant) is redescribed with
      additional taxonomic details, morphometrics, and illustrations. It is also
      recorded for the first time from India. 

PMID- 24870502
TI  - A new species of Minagenia Banks, 1934 (Hymenoptera, Pompilidae) from China, with
      the key to species.
AB  - Minagenia fulvifemoralis Ji et Ma, sp. nov. (Yunnan) is described and figured.
      Key to five species of the genus Minagenia Banks is given. 

PMID- 24870503
TI  - A new species of Hoeneidia (Lepidoptera: Noctuidae, Noctuinae: Noctuini) from
      China.

PMID- 24870504
TI  - Onthophagus fragosus n.sp. a second endemic species of Onthophagus Latreille from
      Cuba (Coleoptera : Scarabaeidae, Scarabaeinae).
AB  - Onthophagus fragosus, a new species of Onthophagus, is described from Cienfuegos
      Province on the island of Cuba. Specimens were collected in leaf litter samples
      at elevations of 650-935 m. It appears to be most closely related to O.
      marginatus Castelnau, the only other Cuban endemic Onthophagus species. Images of
      habitus and of male genitalia are provided.  

PMID- 24870506
TI  - Redacted policy on sharing drug trial data in Europe.

PMID- 24870508
TI  - China must continue the momentum of green law.

PMID- 24870507
TI  - Effect of raw milk on allergic responses in a murine model of gastrointestinal
      allergy.
AB  - Epidemiological studies have shown an association between the consumption of raw
      farm milk and reduced incidence of allergy. In the present study, we fed
      untreated raw milk, gamma-sterilised milk, heat-treated milk or water to mice and
      compared their responses to allergen exposure and challenge treatment in a mouse
      model of gastrointestinal allergy. From weaning (3 weeks old), groups of BALB/c
      female mice (n 8) received raw milk, gamma-sterilised milk, heated milk or water
      via drink bottles, with the control group receiving water. All mice were fed a
      standard (dairy protein-free) rodent diet. At 6 and 8 weeks, groups were given
      intra-peritoneal injections with ovalbumin (OVA)/alum to sensitise them to the
      antigen. Controls were sham immunised. At week 10, mice were fasted and
      challenged four times on alternate days by intra-gastric administration with 50
      mg OVA or saline. Levels of bacteria and milk proteins were assessed in milk
      samples. Mouse serum levels of specific IgE, IgG1 and IgG2a antibodies and mouse
      mast cell protease-1 (MMCP-1) were determined. Cytokine responses to 48 h
      activation with OVA were measured in cultured splenocytes from mice. Sterilised
      and heated milks contained no viable bacteria and reduced detectable levels of
      many milk proteins, in contrast to raw milk. Mice drinking raw milk had highest
      serum MMCP-1 and specific-OVA IgE responses. Cultured splenocytes from OVA-primed
      mice produced similar levels of IL-4 in response to the antigen; however, IL-10
      levels were highest from mice drinking raw milk. Overall, the present study adds
      to the evidence that consuming different types of milk can affect allergic
      responses to a non-related dietary antigen.

PMID- 24870520
TI  - Old cancer drug gets fresh look.

PMID- 24870521
TI  - US Arctic research ship ready to cast off.

PMID- 24870522
TI  - Cloud computing beckons scientists.

PMID- 24870523
TI  - Biomedical institute opens its doors to physicists.

PMID- 24870524
TI  - Chicken project gets off the ground.

PMID- 24870527
TI  - Theoretical physics: Complexity on the horizon.

PMID- 24870526
TI  - Global health: Deadly dinners.

PMID- 24870530
TI  - Q&A: The space crusader.

PMID- 24870531
TI  - China: Tackle pollution from solar panels.

PMID- 24870532
TI  - Medical research: US patient network safeguards data.

PMID- 24870533
TI  - Public outreach: Industries depend on biodiversity too.

PMID- 24870534
TI  - Ecology: Stop Madagascar's toad invasion now.

PMID- 24870535
TI  - Douglas Coleman (1931-2014).

PMID- 24870536
TI  - Materials science: Energy storage wrapped up.

PMID- 24870538
TI  - Precision measurement: The magnetic proton.

PMID- 24870539
TI  - Cardiovascular biology: Switched at birth.

PMID- 24870540
TI  - Immunology: To affinity and beyond.

PMID- 24870544
TI  - Three regimes of extrasolar planet radius inferred from host star metallicities.
AB  - Approximately half of the extrasolar planets (exoplanets) with radii less than
      four Earth radii are in orbits with short periods. Despite their sheer abundance,
      the compositions of such planets are largely unknown. The available evidence
      suggests that they range in composition from small, high-density rocky planets to
      low-density planets consisting of rocky cores surrounded by thick hydrogen and
      helium gas envelopes. Here we report the metallicities (that is, the abundances
      of elements heavier than hydrogen and helium) of more than 400 stars hosting 600
      exoplanet candidates, and find that the exoplanets can be categorized into three
      populations defined by statistically distinct (~4.5sigma) metallicity regions. We
      interpret these regions as reflecting the formation regimes of terrestrial-like
      planets (radii less than 1.7 Earth radii), gas dwarf planets with rocky cores and
      hydrogen-helium envelopes (radii between 1.7 and 3.9 Earth radii) and ice or gas
      giant planets (radii greater than 3.9 Earth radii). These transitions correspond
      well with those inferred from dynamical mass estimates, implying that host star
      metallicity, which is a proxy for the initial solids inventory of the
      protoplanetary disk, is a key ingredient regulating the structure of planetary
      systems. 

PMID- 24870543
TI  - Mass-spectrometry-based draft of the human proteome.
AB  - Proteomes are characterized by large protein-abundance differences, cell-type-
      and time-dependent expression patterns and post-translational modifications, all
      of which carry biological information that is not accessible by genomics or
      transcriptomics. Here we present a mass-spectrometry-based draft of the human
      proteome and a public, high-performance, in-memory database for real-time
      analysis of terabytes of big data, called ProteomicsDB. The information assembled
      from human tissues, cell lines and body fluids enabled estimation of the size of
      the protein-coding genome, and identified organ-specific proteins and a large
      number of translated lincRNAs (long intergenic non-coding RNAs). Analysis of
      messenger RNA and protein-expression profiles of human tissues revealed conserved
      control of protein abundance, and integration of drug-sensitivity data enabled
      the identification of proteins predicting resistance or sensitivity. The proteome
      profiles also hold considerable promise for analysing the composition and
      stoichiometry of protein complexes. ProteomicsDB thus enables navigation of
      proteomes, provides biological insight and fosters the development of proteomic
      technology. 

PMID- 24870545
TI  - Direct high-precision measurement of the magnetic moment of the proton.
AB  - One of the fundamental properties of the proton is its magnetic moment, up. So
      far up has been measured only indirectly, by analysing the spectrum of an atomic
      hydrogen maser in a magnetic field. Here we report the direct high-precision
      measurement of the magnetic moment of a single proton using the double Penning
      trap technique. We drive proton-spin quantum jumps by a magnetic radio-frequency
      field in a Penning trap with a homogeneous magnetic field. The induced spin
      transitions are detected in a second trap with a strong superimposed magnetic
      inhomogeneity. This enables the measurement of the spin-flip probability as a
      function of the drive frequency. In each measurement the proton's cyclotron
      frequency is used to determine the magnetic field of the trap. From the
      normalized resonance curve, we extract the particle's magnetic moment in terms of
      the nuclear magneton: MUp = 2.792847350(9)MUN. This measurement outperforms
      previous Penning-trap measurements in terms of precision by a factor of about
      760. It improves the precision of the forty-year-old indirect measurement, in
      which significant theoretical bound state corrections were required to obtain up,
      by a factor of 3. By application of this method to the antiproton magnetic
      moment, the fractional precision of the recently reported value can be improved
      by a factor of at least 1,000. Combined with the present result, this will
      provide a stringent test of matter/antimatter symmetry with baryons. 

PMID- 24870546
TI  - Storm-induced sea-ice breakup and the implications for ice extent.
AB  - The propagation of large, storm-generated waves through sea ice has so far not
      been measured, limiting our understanding of how ocean waves break sea ice.
      Without improved knowledge of ice breakup, we are unable to understand recent
      changes, or predict future changes, in Arctic and Antarctic sea ice. Here we show
      that storm-generated ocean waves propagating through Antarctic sea ice are able
      to transport enough energy to break sea ice hundreds of kilometres from the ice
      edge. Our results, which are based on concurrent observations at multiple
      locations, establish that large waves break sea ice much farther from the ice
      edge than would be predicted by the commonly assumed exponential decay. We
      observed the wave height decay to be almost linear for large waves--those with a
      significant wave height greater than three metres--and to be exponential only for
      small waves. This implies a more prominent role for large ocean waves in sea-ice
      breakup and retreat than previously thought. We examine the wider relevance of
      this by comparing observed Antarctic sea-ice edge positions with changes in
      modelled significant wave heights for the Southern Ocean between 1997 and 2009,
      and find that the retreat and expansion of the sea-ice edge correlate with mean
      significant wave height increases and decreases, respectively. This includes
      capturing the spatial variability in sea-ice trends found in the Ross and
      Amundsen-Bellingshausen seas. Climate models fail to capture recent changes in
      sea ice in both polar regions. Our results suggest that the incorporation of
      explicit or parameterized interactions between ocean waves and sea ice may
      resolve this problem.

PMID- 24870547
TI  - Proteomics: An atlas of expression.

PMID- 24870542
TI  - A draft map of the human proteome.
AB  - The availability of human genome sequence has transformed biomedical research
      over the past decade. However, an equivalent map for the human proteome with
      direct measurements of proteins and peptides does not exist yet. Here we present
      a draft map of the human proteome using high-resolution Fourier-transform mass
      spectrometry. In-depth proteomic profiling of 30 histologically normal human
      samples, including 17 adult tissues, 7 fetal tissues and 6 purified primary
      haematopoietic cells, resulted in identification of proteins encoded by 17,294
      genes accounting for approximately 84% of the total annotated protein-coding
      genes in humans. A unique and comprehensive strategy for proteogenomic analysis
      enabled us to discover a number of novel protein-coding regions, which includes
      translated pseudogenes, non-coding RNAs and upstream open reading frames. This
      large human proteome catalogue (available as an interactive web-based resource at
      http://www.humanproteomemap.org) will complement available human genome and
      transcriptome data to accelerate biomedical research in health and disease. 

PMID- 24870549
TI  - Familial hypercholesterolaemia.
AB  - PURPOSE OF REVIEW: Familial hypercholesterolaemia is associated with lifelong
      elevated cholesterol levels and is an important cause of premature coronary heart
      disease (CHD). This condition is often underdiagnosed and undertreated. Awareness
      of this condition is poor among nonlipid specialists. Treatment of elevated
      cholesterol levels with statins reduces the risk for CHD. The review will
      increase the awareness of this condition among nonspecialists. RECENT FINDINGS:
      Recently, several guidelines have been produced by different countries, but a
      unified approach to this global problem is addressed through a recent guideline
      facilitated by the Familial Hypercholesterolaemia Foundation. Although the
      widespread use of statins has been successful in reducing the risk for CHD in
      familial hypercholesterolaemia, there have been difficulties in getting to
      targets, especially in those with established vascular disease. New therapies
      such as mipomersen, a second-generation antisense oligonucleotide, microsomal
      triglyceride transfer protein inhibitors that decrease the synthesis of
      apolipoprotein B-containing lipoproteins and proprotein convertase
      subtilisin/kexin type 9 inhibitors hold promise in reducing cholesterol levels in
      those patients in whom low density lipoprotein cholesterol (LDL-C) reduction is
      required beyond the use of statins, especially in those with severe heterozygous
      familial hypercholesterolaemia or homozygous familial hypercholesterolaemia.
      SUMMARY: Increased awareness and wider availability of guidance to treat familial
      hypercholesterolaemia will improve management of familial hypercholesterolaemia.
      New therapies, if they become available after appropriate outcome studies, will
      reduce LDL-C levels in both homozygous familial hypercholesterolaemia and severe
      heterozygous familial hypercholesterolaemia, thus reducing the risk for premature
      CHD.

PMID- 24870550
TI  - Selected natural phenolic compounds - potential treatment for peripheral
      neuropathy?
AB  - Neuropathic pain is a syndrome comprising pain caused by a lesion or dysfunction
      of the nervous system, or resulting from lesions or diseases of the somatosensory
      system. Neuropathic pain is often connected with adverse effects of chemotherapy
      administered because of cancer, infiltration of the nervous tissue with cancer
      cells, neurodegeneration and diabetes mellitus. Disbalance in the production of
      various cytokines plays an important role in the pathogenesis of many of the
      diseases connected with neuropathies. These cytokines comprise in particular
      interleukins IL-1beta, IL-15, and IL-6, tumour necrosis factors, and
      prostaglandins. The biochemistry of the production of cytokines is directed by
      nuclear factors, which affect the expression of the mRNA for the respective
      cytokines or enzymes metabolizing the cytokines. The main nuclear factor which
      regulates the expression of cytokines is NF-kappaB. Because of insufficient
      effectiveness or adverse effects of the pharmacological treatment of peripheral
      neuropathy, many patients seek supportive or adjuvant therapy. Natural compounds
      which modulate the production of inflammatory cytokines may reduce the symptoms
      of neuropathies. Many natural phenolic compounds belong to substances affecting
      the activity of NF-kappaB and consequently the activity of cytokines which are
      regulated by this substance. The aim of this mini-review is to present
      information about three natural phenols which are potentially usable for the
      treatment of neuropathies: curcumin, resveratrol and mangiferin, and bring
      attention to the practical usability thereof. Curcumin and mangiferin are active
      constituents of plants; they have been used for centuries in traditional
      medicine. Biological effects of resveratrol have been known for a relatively
      short time; since the discovery of the so-called French paradox, attention has
      been focused on resveratrol. This summary includes particularly the information
      related to the influence on the activity of NF-kappaB, expression of anti
      inflammatory cytokines, and antiradical activity, because imbalance between the
      creation and degradation of free radicals plays an important role in the
      activation of NF-kappaB and in inflammatory processes. It also briefly summarizes
      basic information concerning bioavailability, metabolism and practical
      application of the aforementioned substances. KEYWORDS: phenols curcumin
      mangiferin NF-kappaB peripheral neuropathy resveratrol.

PMID- 24870551
TI  - Active pharmaceutical ingredients available as substances for extemporaneous
      preparation in veterinary medicine in the Czech Republic.
AB  - In veterinary medicine, extemporaneously prepared drugs can be also used in
      therapy. In the recent four years the selection of suitable compounds for
      extemporaneous (magistral) preparation has been expanded and new possibilities
      for the creation of formulas have appeared. The paper reports on the substances
      available for compounding that can be used in veterinary medicine, in the
      pharmacotherapeutic classes antibiotics, antimycotics, antiseptics,
      corticosteroids, emollients and epithelizing agents, anti-inflammatory drugs,
      local anesthetics, decongestives, beta-blockers and calcium channel blockers,
      antiemetics and prokinetics, sedatives and hypnotics. The emphasis has been
      placed on newly available substances. Examples of suitable magistral formulas are
      presented that can replace mass-produced drug products which are not readily
      obtainable. The aim of the paper is to inform pharmacists and veterinarians about
      new possibilities of drug compounding. KEYWORDS: compounded preparations
      extemporaneous preparation compounding of drugs possibilities magistral formulas
      in veterinary medicine.

PMID- 24870552
TI  - [Possibilities of influencing the drug content and encapsulation efficiency of
      chitosan microspheres prepared by ionic gelation process].
AB  - This study aimed to prepare high molecular weight chitosan blank and drug-loaded
      microparticles using 5-aminosalicylic acid (5-ASA) as the model active substance
      by an external ionic gelation. Formulation and process variables included the
      chitosan concentration and presence of drug in the polymer solution, and/or in
      hardening solution during the microparticles preparation. The effect of different
      preparation conditions on the properties of the microparticles was observed with
      a view to increase drug content in microparticles. For both types of
      microparticles (with and without the drug), it was found that their sphericity
      and equivalent diameter increased with increasing chitosan concentration. The
      drug content of drug-loaded microparticles was the highest in the case of the
      sample prepared from 1.75% chitosan dispersion, when the drug was present both in
      the chitosan dispersion and the hardening solution. Maximum six times higher drug
      content was achieved by change of the placement of 5-ASA during preparation
      (1.25% chitosan concentration). KEYWORDS: microparticles external ionotropic
      gelation chitosan 5-ASA encapsulation efficiency.

PMID- 24870554
TI  - [History of the development and production of drugs in the firm Lachema in Brno].
AB  - Since the 1980 year Lachema Brno was ranked among the leading pharmaceutical
      companies in Czechoslovakia. Lachema was founded already in 1951 but the modern
      factory was built around the Research Institute in the 1970s. Although Lachema
      existed separately, it became the property of Chemapol after privatization. After
      bankruptcy of Chemapol, Lachema was purchased by the largest Eastern European
      generic company Pliva. In 2006 Pliva became part of the U.S. generic
      pharmaceutical company Barr Pharmaceuticals. Finally, in 2008, Barr was acquired
      by Teva and Lachema was subsequently shut down. Although in the Czech Republic
      Lachema was almost the monopoly producer of cytostatics and a developer of
      original drugs, there is no separate mention about it in The History of Pharmacy
      in the Czech Countries. This paper therefore briefly summarizes the period of its
      existence, describes the research and production of pharmaceuticals and mentions
      a few, but not all, key personalities in the development and production of
      drugs.Keyword: Lachema history research industry cytostatics. 

PMID- 24870553
TI  - [Medical and entrepreneurial character of the community pharmacy].
AB  - Community pharmacy provides citizens with pharmaceutical care and runs its health
      care business on the market with state regulatory interventions. These
      restrictions affect its stability and because of that it has to be constantly
      monitored. The convenient way of monitoring the financial health of a community
      pharmacy is the use of financial analysis and its outcomes that are
      profitability, liquidity, debt and productivity ratios. The aim of this paper was
      to determine the economic situation in the public pharmacy services in Slovakia.
      A representative set of community pharmacies was established that reflected the
      criteria of localization by regions in Slovakia, the size of the city or
      municipality and the legal form of the subject. The financial analysis for the
      years 2007-2012 showed a declining return on sales (in 2012 to 1.98 %), a
      decreasing current liquidity (in 2012 to 1.87 %), a declining quick ratio (in
      2012 to 1.08 %), a decrease in the time receivables turnover (in 2012 to 53.8
      days), a slight increase in the inventory turnover time - days sales in inventory
      (in 2012 to 36.5 days) and increased turnover time commitments - liabilities
      turnover (in 2012 to 86.3 days). KEYWORDS: community pharmacy financial health
      profitability liquidity productivity.

PMID- 24870555
TI  - Influence of the glass transition on rotational dynamics of dyes in thin polymer
      films: single-molecule and ensemble experiments.
AB  - We performed polarized fluorescence emission studies of Nile Red (NR) in
      poly(methyl methacrylate) (PMMA), poly(ethyl methacrylate) (PEMA), and poly(butyl
      methacrylate) (PBMA) at the single molecule (SM) and at the ensemble level to
      study the in cage movements of the ground-state molecule in polymer films of
      nanometric thickness at room temperature. Experiments were performed with wide
      field irradiation. At the ensemble level, the linearly polarized irradiation was
      used to induce a photoselection by bleaching, which is compensated by rotational
      diffusion. Both results show an appreciable difference in mobility of NR in the
      films that is correlated with the different glass-transition temperatures of the
      films, particularly in PEMA, which displays a clearly distinct behavior between
      the 200 nm films, representing a rigid environment, and the 25 nm ones, showing
      much higher mobility. We developed a model of broad application for polarized
      photobleaching that allows obtaining rotational diffusion coefficients and
      photobleaching quantum yields in an easy way from ensemble experiments. The
      parameters obtained from ensemble measurements correlate well with the results
      from SM experiments. 

PMID- 24870557
TI  - Resolving the electrospinnability zones and diameter prediction for the
      electrospinning of the gelatin/water/acetic acid system.
AB  - The development of suitable biomimetic scaffolds is a fundamental requirement of
      tissue engineering. Although electrospinning has emerged as an effective method
      for producing such scaffolds of nanometer-sized fibers, the influence of solution
      characteristics on the morphology of the resulting nanofibers depends on each
      polymer solution system. In this study, gelatin nanofibers and microfibers were
      prepared via electrospinning using mixtures of water and acetic acid at different
      ratios as solvents. The viscosities of gelatin solutions before electrospinning
      were analyzed and two different behaviors were found as a function of the solvent
      composition, taking into account classic models of polymer science. A power law
      relationship between viscosity and gelatin concentration was found for each
      solvent system, and an empirical model including the influence of acetic acid was
      obtained for aqueous systems. Moreover, a ternary diagram considering gelatin,
      water, and acetic acid mass fractions was constructed as a tool to establish the
      electrospinnability domains in terms of fiber occurrence and morphology. Also,
      the isodiametric curves were defined in the fibers region. Finally, in order to
      correlate the diameter of electrospun nanofibers and the electrospinnability
      zones, the Berry number was used. However, as its only allows the range of
      electrospinnability to be established for a fixed solvent composition, a new
      dimensionless parameter (Bemod) was suggested to take into account all the acetic
      acid aqueous solutions as a single solvent. 

PMID- 24870556
TI  - Breast cancer metastasis: demonstration that FOXP3 regulates CXCR4 expression and
      the response to CXCL12.
AB  - The X-linked transcription factor FOXP3 is expressed by epithelial cells of
      organs including the breast, where it is considered a tumour suppressor. The
      chemokine receptor CXCR4 also regulates the development of breast cancer by
      stimulating cell migration towards CXCL12-expressing sites of metastatic spread.
      During activation, human T cells show reciprocal regulation of FOXP3 and CXCR4.
      This study was designed to examine the role FOXP3 plays in metastatic breast
      cancer, with a particular focus on its potential to regulate CXCR4. Human breast
      cancer samples showed significantly decreased FOXP3 protein expression but an
      increased number of CXCR4 transcripts. In comparison with normal primary breast
      epithelial cells, FOXP3 was down-regulated at both transcript and protein levels
      in the breast cancer cell lines MCF-7 and MDA-MB-231. In the invasive MDA-MB-231
      cells, the remaining FOXP3 was located predominately within the cytoplasm.
      Following stable FOXP3 overexpression in MDA-MB-231 cells, significant decreases
      were observed in the expression of ErbB2/HER2, SKP2, c-MYC, and CXCR4. In
      contrast, an increase in p21 expression led to inhibition of cell proliferation,
      with a greater proportion in the G1 phase of the cell cycle suggesting the
      induction of senescence. Specific knockdown of FOXP3 in normal human breast
      epithelial cells with siRNA significantly increased ErbB2/HER2, SKP2, c-MYC, and
      CXCR4, and decreased p21 expression. These cells also showed a significantly
      increased chemotactic response towards CXCL12, consistent with a role for FOXP3
      in the regulation of cell migration. Results from this study are consistent with
      FOXP3 functioning as an important tumour suppressor in breast cancer. Indeed, the
      potential functions of FOXP3 in breast epithelium can now be extended to include
      regulation of CXCR4 expression and response to the pro-metastatic chemokine
      CXCL12.

PMID- 24870559
TI  - Afatinib in the treatment of breast cancer.
AB  - INTRODUCTION: Trastuzumab has dramatically improved outcomes for those diagnosed
      with human EGFR2 (HER2)-positive breast cancer. Resistance to trastuzumab,
      however, is an ongoing problem that has led to the development of a number of new
      HER2-targeted therapies. Afatinib is a novel, orally bioavailable irreversible
      pan-HER inhibitor that has been evaluated in multiple tumor types. It has also
      shown promise in NSCLC where it has earned FDA approval. Its activity in breast
      cancer is currently being evaluated. AREAS COVERED: This review briefly
      summarizes the current therapies available for HER2-positive metastatic disease.
      This article also describes the data available for afatinib in breast cancer from
      preclinical analyses, published Phase I and II trials to ongoing and upcoming
      Phase II and III studies. EXPERT OPINION: While Phase I and II studies have
      demonstrated promising activity in HER2-positive breast cancer, the Phase III
      randomized study of afatinib in trastuzumab-resistant metastatic breast cancer
      was halted early due to unfavorable risk-benefit analysis from the Independent
      Data Monitoring Committee (IDMC). The successful development of afatinib in
      breast cancer will thus depend on aggressively preventing and managing its
      associated toxicities.

PMID- 24870560
TI  - Categorical biases in perceiving spatial relations.
AB  - We investigate the effect of spatial categories on visual perception. In three
      experiments, participants made same/different judgments on pairs of
      simultaneously presented dot-cross configurations. For different trials, the
      position of the dot within each cross could differ with respect to either
      categorical spatial relations (the dots occupied different quadrants) or
      coordinate spatial relations (the dots occupied different positions within the
      same quadrant). The dot-cross configurations also varied in how readily the dot
      position could be lexicalized. In harder-to-name trials, crosses formed a "+"
      shape such that each quadrant was associated with two discrete lexicalized
      spatial categories (e.g., "above" and "left"). In easier-to-name trials, both
      crosses were rotated 45 degrees  to form an "*" shape such that quadrants were
      unambiguously associated with a single lexicalized spatial category (e.g.,
      "above" or "left"). In Experiment 1, participants were more accurate when
      discriminating categorical information between easier-to-name categories and more
      accurate at discriminating coordinate spatial information within harder-to-name
      categories. Subsequent experiments attempted to down-regulate or up-regulate the
      involvement of language in task performance. Results from Experiment 2 (verbal
      interference) and Experiment 3 (verbal training) suggest that the observed
      spatial relation type-by-nameability interaction is resistant to online language
      manipulations previously shown to affect color and object-based perceptual
      processing. The results across all three experiments suggest that robust biases
      in the visual perception of spatial relations correlate with patterns of
      lexicalization, but do not appear to be modulated by language online. 

PMID- 24870562
TI  - Radiation-induced DNA damage and the relative biological effectiveness of 18F-FDG
      in wild-type mice.
AB  - Clinically, the most commonly used positron emission tomography (PET) radiotracer
      is the glucose analog 2-[(18)F] fluoro-2-deoxy-D-glucose ((18)F-FDG), however
      little research has been conducted on the biological effects of (18)F-FDG
      injections. The induction and repair of DNA damage and the relative biological
      effectiveness (RBE) of radiation from (18)F-FDG relative to 662 keV gamma-rays
      were investigated. The study also assessed whether low-dose radiation exposure
      from (18)F-FDG was capable of inducing an adaptive response. DNA damage to the
      bone marrow erythroblast population was measured using micronucleus formation and
      lymphocyte gammaH2A.X levels. To test the RBE of (18)F-FDG, mice were injected
      with a range of activities of (18)F-FDG (0-14.80 MBq) or irradiated with Cs-137
      gamma-rays (0-100 mGy). The adaptive response was investigated 24h after the
      (18)F-FDG injection by 1 Gy in vivo challenge doses for micronucleated
      reticulocyte (MN-RET) formation or 1, 2 and 4 Gy in vitro challenges doses for
      gammaH2A.X formation. A significant increase in MN-RET formation above controls
      occurred following injection activities of 3.70, 7.40 or 14.80 MBq (P < 0.001)
      which correspond to bone marrow doses of ~35, 75 and 150 mGy, respectively. Per
      unit dose, the Cs-137 radiation exposure induced significantly more damage than
      the (18)F-FDG injections (RBE = 0.79 +/- 0.04). A 20% reduction in gammaH2A.X
      fluorescence was observed in mice injected with a prior adapting low dose of
      14.80 MBq (18)F-FDG relative to controls (P < 0.019). A 0.74 MBq (18)F-FDG
      injection, which gives mice a dose approximately equal to a typical human PET
      scan, did not cause a significant increase in DNA damage nor did it generate an
      adaptive response. Typical (18)F-FDG injection activities used in small animal
      imaging (14.80 MBq) resulted in a decrease in DNA damage, as measured by
      gammaH2A.X formation, below spontaneous levels observed in control mice. The
      (18)F-FDG RBE was <1.0, indicating that the mixed radiation quality and/or low
      dose rate from PET scans is less damaging than equivalent doses of gamma
      radiation.

PMID- 24870561
TI  - Dyrk1A induces pancreatic beta cell mass expansion and improves glucose
      tolerance.
AB  - Type 2 diabetes is caused by a limited capacity of insulin-producing pancreatic
      beta cells to increase their mass and function in response to insulin resistance.
      The signaling pathways that positively regulate functional beta cell mass have
      not been fully elucidated. DYRK1A (also called minibrain/MNB) is a member of the
      dual-specificity tyrosine phosphorylation-regulated kinase (DYRK) family. A
      significant amount of data implicates DYRK1A in brain growth and Down syndrome,
      and recent data indicate that Dyrk1A haploinsufficient mice have a low functional
      beta cell mass. Here we ask whether Dyrk1A upregulation could be a way to
      increase functional beta cell mass. We used mice overexpressing Dyrk1A under the
      control of its own regulatory sequences (mBACTgDyrk1A). These mice exhibit
      decreased glucose levels and hyperinsulinemia in the fasting state. Improved
      glucose tolerance is observed in these mice as early as 4 weeks of age.
      Upregulation of Dyrk1A in beta cells induces expansion of beta cell mass through
      increased proliferation and cell size. Importantly, mBACTgDyrk1A mice are
      protected against high-fat-diet-induced beta cell failure through increase in
      beta cell mass and insulin sensitivity. These studies show the crucial role of
      the DYRK1A pathway in the regulation of beta cell mass and carbohydrate
      metabolism in vivo. Activating the DYRK1A pathway could thus represent an
      innovative way to increase functional beta cell mass.

PMID- 24870563
TI  - Low-dose radiation from 18F-FDG PET does not increase cancer frequency or shorten
      latency but reduces kidney disease in cancer-prone Trp53+/- mice.
AB  - There is considerable interest in the health effects associated with low-level
      radiation exposure from medical imaging procedures. Concerns in the medical
      community that increased radiation exposure from imaging procedures may increase
      cancer risk among patients are confounded by research showing that low-dose
      radiation exposure can extend lifespan by increasing the latency period of some
      types of cancer. The most commonly used radiopharmaceutical for positron emission
      tomography (PET) scans is 2-[(18)F] fluoro-2-deoxy-d-glucose ((18)F-FDG), which
      exposes tissue to a low-dose, mixed radiation quality: 634 keV beta+ and 511 keV
      gamma-rays. The goal of this research was to investigate how modification of
      cancer risk associated with exposure to low-dose ionising radiation in cancer
      prone Trp53+/- mice is influenced by radiation quality from PET. At 7-8 weeks of
      age, Trp53+/- female mice were exposed to one of five treatments: 0 Gy, 10 mGy
      gamma-rays, 10 mGy (18)F-FDG, 4 Gy gamma-rays, 10 mGy (18)F-FDG + 4 Gy gamma-rays
      (n > 185 per group). The large 4-Gy radiation dose significantly reduced the
      lifespan by shortening the latency period of cancer and significantly increasing
      the number of mice with malignancies, compared with unirradiated controls. The 10
      mGy gamma-rays and 10 mGy PET doses did not significantly modify the frequency or
      latency period of cancer relative to unirradiated mice. Similarly, the PET scan
      administered prior to a large 4-Gy dose did not significantly modify the latency
      or frequency of cancer relative to mice receiving a dose of only 4 Gy. The
      relative biological effectiveness of radiation quality from (18)F-FDG, with
      respect to malignancy, is approximately 1. However; when non-cancer endpoints
      were studied, it was found that the 10-mGy PET group had a significant reduction
      in kidney lesions (P < 0.021), indicating that a higher absorbed dose (20 +/-
      0.13 mGy), relative to the whole-body average, which occurs in specific tissues,
      may not be detrimental.

PMID- 24870564
TI  - Dynamic knee joint mechanics after anterior cruciate ligament reconstruction.
AB  - PURPOSE: There is scarcity of information on the long-term adaptations in lower
      limb biomechanics during game-specific movements after anterior cruciate ligament
      (ACL) reconstruction. Particularly, variables such as knee abduction moments and
      transverse plane knee motion have not been studied during a game-specific landing
      and cutting task after ACL reconstruction. The purpose of this study was to
      compare the hip and knee mechanics between the ACL-reconstructed (ACLr) group and
      a healthy control group. METHODS: Thirty-eight reconstructed athletes (18 ACLr,
      18 control) participated in the study. Three-dimensional hip, knee, and ankle
      angles were calculated during a maximal drop jump land from a 0.30-m box and
      unanticipated cutting task at 45 degrees . RESULTS: During the landing phase,
      ACLr participants had increased hip flexion (P < 0.003) and transverse plane knee
      range of motion (P = 0.027). During the cutting phase, the ACLr participant's
      previously injured limb had increased internal knee abduction moment compared
      with that of the control group (P = 0.032). No significant differences were
      reported between the previously injured and contralateral uninjured limb.
      CONCLUSIONS: Previously injured participants demonstrated higher knee abduction
      moment and transverse plane range of motion when compared with those of control
      participants during a game-specific landing and cutting task.

PMID- 24870565
TI  - High twin resemblance for sensitivity to hypoxia.
AB  - PURPOSE: Physiological responses to hypoxia vary between individuals, and genetic
      factors are conceivably involved. Using a monozygotic twin design, we
      investigated the role of genetic factors in physiological responses to acute
      hypoxia. METHODS: Thirteen pairs of monozygotic twin brothers participated in two
      experimental sessions in a normobaric hypoxic facility with a 2-wk interval. In
      one session, fraction of inspired O2 (FiO2) was gradually reduced to 10.7%
      (approximately 5300 m altitude) over 5 h. During the next 3 h at 10.7%, FiO2
      subjects performed a 20-min submaximal exercise bout (EXSUB, 1.2 W.kg) and a
      maximal incremental exercise test (EXMAX). An identical control experiment was
      done in normoxia. Cardiorespiratory measurements were continuously performed, and
      8-h urine output was collected. RESULTS: Compared with normoxia, hypoxia
      decreased (P < 0.05) arterial O2 saturation (%SpO2) at rest (-22%) and during
      exercise (-28%). Furthermore, VO2max (-39%), HRmax (HR, -8%), maximal pulmonary
      ventilation (VEmax, -11%), and urinary norepinephrine excretion (-31%) were
      reduced (P < 0.05) whereas HR at rest (25%) and during EXSUB (16%) and VE at rest
      (38%) and during EXSUB (70%) were increased (P < 0.05). However, hypoxia-induced
      changes (Delta) were not randomly distributed between subjects. Between-pair
      variance was substantially larger than within-pair variance (P < 0.05) for
      Delta%SpO2 at rest (approximately threefold) and during exercise (approximately
      fourfold), DeltaVO2max (approximately fourfold), DeltaHR during exercise
      (approximately seven- to eightfold), hypoxic ventilatory response (approximately
      sixfold), and Delta urinary norepinephrine output (approximately threefold).
      Incidence of acute mountain sickness (AMS) also yielded significant twin
      similarity (P < 0.05). AMS subjects showed approximately 50% greater drop in
      urinary norepinephrine and lower hypoxic ventilator response than AMS
      individuals. CONCLUSIONS: Our data suggest that genetic factors regulate
      cardiorespiratory responses, exercise tolerance, and pathogenesis of AMS symptoms
      in acute severe hypoxia. Hypoxia-induced sympathetic downregulation was
      associated with AMS.

PMID- 24870566
TI  - Effect of rocker-soled shoes on parameters of knee joint load in knee
      osteoarthritis.
AB  - PURPOSE: This study evaluated the immediate effects of rocker-soled shoes on
      parameters of the knee adduction moment (KAM) and pain in individuals with knee
      osteoarthritis (OA). METHODS: Three-dimensional gait analysis was performed on 30
      individuals (mean (SD): age, 61 (7) yr; 15 (50%) male) with radiographic and
      symptomatic knee OA under three walking conditions in a randomized order: i)
      wearing rocker-soled shoes (Skechers Shape-ups), ii) wearing non-rocker-soled
      shoes (ASICS walking shoes), and iii) barefoot. Peak KAM and KAM angular impulse
      were measured as primary indicators of knee load distribution. Secondary measures
      included the knee flexion moment (KFM) and knee pain during walking. RESULTS:
      Peak KAM was significantly lower when wearing the rocker-soled shoes compared
      with that when wearing the non-rocker-soled shoes (mean difference (95%
      confidence interval), -0.27 (-0.42 to -0.12) N.m/BW * Ht%; P < 0.001). Post hoc
      tests revealed no significant difference in KAM impulse between rocker-soled and
      non-rocker-soled shoe conditions (P = 0.13). Both peak KAM and KAM impulse were
      significantly higher during both shoe conditions compared with those during the
      barefoot condition (P < 0.001). There were no significant differences in KFM (P =
      0.36) or knee pain (P = 0.89) between conditions. CONCLUSIONS: Rocker-soled shoes
      significantly reduced peak KAM when compared with non-rocker-soled shoes, without
      a concomitant change in KFM, and thus may potentially reduce medial knee joint
      loading. However, KAM parameters in the rocker-soled shoes remained significantly
      higher than those during barefoot walking. Wearing rocker-soled shoes did not
      have a significant immediate effect on walking pain. Further research is required
      to evaluate whether rocker-soled shoes can influence symptoms and progression of
      knee OA with prolonged wear.

PMID- 24870567
TI  - Inspiratory muscle training affects proprioceptive use and low back pain.
AB  - PURPOSE: We have shown that individuals with recurrent nonspecific low back pain
      (LBP) and healthy individuals breathing against an inspiratory load decrease
      their reliance on back proprioceptive signals in upright standing. Because
      individuals with LBP show greater susceptibility to diaphragm fatigue, it is
      reasonable to hypothesize that LBP, diaphragm dysfunction, and proprioceptive use
      may be interrelated. The purpose of this study was to investigate whether
      inspiratory muscle training (IMT) affects proprioceptive use during postural
      control in individuals with LBP. METHODS: Twenty-eight individuals with LBP were
      assigned randomly into a high-intensity IMT group (high IMT) and low-intensity
      IMT group (low IMT). The use of proprioception in upright standing was evaluated
      by measuring center of pressure displacement during local muscle vibration
      (ankle, back, and ankle-back). Secondary outcomes were inspiratory muscle
      strength, severity of LBP, and disability. RESULTS: After high IMT, individuals
      showed smaller responses to ankle muscle vibration, larger responses to back
      muscle vibration, higher inspiratory muscle strength, and reduced LBP severity (P
      < 0.05). These changes were not seen after low IMT (P > 0.05). No changes in
      disability were observed in either group (P > 0.05). CONCLUSIONS: After 8 wk of
      high IMT, individuals with LBP showed an increased reliance on back
      proprioceptive signals during postural control and improved inspiratory muscle
      strength and severity of LBP, not seen after low IMT. Hence, IMT may facilitate
      the proprioceptive involvement of the trunk in postural control in individuals
      with LBP and thus might be a useful rehabilitation tool for these patients.

PMID- 24870568
TI  - Improved arterial-ventricular coupling in metabolic syndrome after exercise
      training: a pilot study.
AB  - PURPOSE: The metabolic syndrome (MetS) is associated with threefold increased
      risk of cardiovascular (CV) morbidity and mortality, which is partly due to a
      blunted CV reserve capacity, reflected by a reduced peak exercise left
      ventricular (LV) contractility and aerobic capacity and a blunted peak arterial
      ventricular coupling. To date, no study has examined whether aerobic exercise
      training in MetS can reverse peak exercise CV dysfunction. Furthermore, examining
      how exercise training alters CV function in a group of individuals with MetS
      before the development of diabetes and/or overt CV disease can provide insights
      into whether some of the pathophysiological CV changes can be delayed/reversed,
      lowering their CV risk. The objective of this study was to examine the effects of
      8 wk of aerobic exercise training in individuals with MetS on resting and peak
      exercise CV function. METHODS: Twenty participants with MetS underwent either 8
      wk of aerobic exercise training (MetS-ExT, n = 10) or remained sedentary (MetS
      NonT, n = 10) during this period. Resting and peak exercise CV function was
      characterized using Doppler echocardiography and gas exchange. RESULTS: Exercise
      training did not alter resting LV diastolic or systolic function and arterial
      ventricular coupling in MetS. In contrast, at peak exercise, an increase in LV
      contractility (40%, P < 0.01), cardiac output (28%, P < 0.05), and aerobic
      capacity (20%, P < 0.01), but a reduction in vascular resistance (30%, P < 0.05)
      and arterial-ventricular coupling (27%, P < 0.01), were noted in the MetS-ExT but
      not in the MetS-NonT group. Furthermore, an improvement in lifetime risk score
      was also noted in the MetS-ExT group. CONCLUSIONS: These findings have clinical
      importance because they provide insight that some of the pathophysiological
      changes associated with MetS can be improved and can lower the risk of CV
      disease.

PMID- 24870570
TI  - Effect of segmental, localized lower limb cooling on dynamic balance.
AB  - PURPOSE: This study aimed to determine the effect of cooling progressively
      greater portions of the lower extremities on dynamic balance and neuromuscular
      activation. METHODS: Ten healthy males (22.8 +/- 3.4 yr, 76.5 +/- 9.1 kg)
      performed one room air temperature control (22.4 degrees C +/- 0.8 degrees C) and
      three trials of cold water immersion at 12 degrees C (lateral malleolus, ankle;
      lateral femoral epicondyle, knee; anterior superior iliac spine, hip) for 10 min
      before performing a unipedal balance test (Star Excursion Balance Test (SEBT))
      with their dominant limb. Muscle activation of the vastus lateralis, biceps
      femoris, tibialis anterior, and lateral gastrocnemius was measured with surface
      EMG during the SEBT. RESULTS: Core temperature remained euthermic throughout all
      trials. Gastrocnemius temperature decreased from control (30.4 degrees C +/- 0.5
      degrees C) with knee (23.7 degrees C +/- 1.7 degrees C) and hip immersion (22.4
      degrees C +/- 1.0 degrees C), whereas vastus lateralis temperature decreased from
      control (33.7 degrees C +/- 1.7 degrees C) with hip immersion (27.3 degrees C +/-
      2.0 degrees C) (P < 0.01 for all comparisons). Cold water immersion influenced
      mean anterior and posterior reach distance on the SEBT in a dose-dependent
      fashion. Compared with those in control, mean anterior and posterior SEBT reach
      distances were not decreased with ankle (-1.38% and -0.74%, respectively) and
      knee immersion (-2.48% and -2.74%), whereas hip immersion significantly reduced
      SEBT by 4.73% and 4.05% (P < 0.05, d = 0.52-0.58). Muscle activation was largely
      unaffected as the lower extremities were cooled, with only the lateral
      gastrocnemius during the anterior SEBT approaching a decrease (P = 0.059).
      CONCLUSIONS: Cooling larger portions of the lower extremities progressively
      affect dynamic balance, and thermal protection strategies should focus on
      maintaining temperature in the large muscle mass of the thigh.

PMID- 24870569
TI  - Effects of exercise and weight loss in older adults with obstructive sleep apnea.
AB  - PURPOSE: Obstructive sleep apnea (OSA) is prevalent among older individuals and
      is linked to increased cardiovascular disease morbidity. This study examined the
      change in OSA severity after exercise training and dietary-induced weight loss in
      older adults and the association of the changes in OSA severity, body
      composition, and aerobic capacity with arterial distensibility. METHODS: Obese
      adults (n = 25) with OSA, age 60 yr or older, were instructed to participate in
      supervised exercise (3 d.wk) and follow a calorie-restricted diet. Baseline
      assessments of OSA parameters, body weight and composition, aerobic capacity, and
      arterial distensibility were repeated at 12 wk. RESULTS: Nineteen participants
      completed the intervention. At 12 wk, there were reductions in body weight (-9%)
      and percentage of total body fat (-5%) and trunk fat (-8%) whereas aerobic
      capacity improved by 20% (all P < 0.01). The apnea-hypopnea index decreased by 10
      events per hour (P < 0.01) and nocturnal SaO2 (mean SaO2) improved from 94.9% at
      baseline to 95.2% after intervention (P = 0.01). Arterial distensibility for the
      group was not different from that at baseline (P = 0.99), yet individual changes
      in distensibility were associated with the change in nocturnal desaturations (r =
      -0.49, P = 0.03) but not with the change in body weight, apnea-hypopnea index, or
      aerobic capacity. CONCLUSIONS: The severity of OSA was reduced after an exercise
      and weight loss program among older adults, suggesting that this lifestyle
      approach may be an effective first-line nonsurgical and nonpharmacological
      treatment for older patients with OSA.

PMID- 24870571
TI  - Conditioned pain modulation predicts exercise-induced hypoalgesia in healthy
      adults.
AB  - INTRODUCTION: Conditioned pain modulation (CPM) is the concept that pain inhibits
      pain and has potential rehabilitation implications for exercise prescription. The
      purpose of this study was to determine whether changes in pressure pain
      perception after a thermal conditioning stimulus (i.e., CPM) was attenuated with
      aging and whether CPM predicted pain relief after exercise (exercise-induced
      hypoalgesia (EIH)) in healthy young and older adults. METHODS: Twenty young (21.9
      +/- 3.3 yr, 10 men) and 19 older (72.0 +/- 4.5 yr, 10 men) adults participated in
      three sessions: one familiarization and two experimental (EIH and CPM) sessions.
      Pressure pain perception was assessed using a weighted Lucite edge placed on the
      right index finger for 1 min. EIH was determined by measuring pressure pain
      perception before and after prolonged submaximal isometric contraction of the
      elbow flexors. CPM was assessed by measuring pressure pain perception at the
      finger while the foot was immersed in neutral water versus painful ice water.
      RESULTS: Young, but not older, adults reported a decrease in pressure pain at the
      finger while their foot was immersed in the ice water bath compared with the
      neutral bath (i.e., CPM, trial-age: P = 0.001). Pressure pain ratings decreased
      after exercise (P = 0.03) that was perceived as painful (peak arm pain, 7.0 +/-
      3.3) for both young and older adults. Regression analysis showed that after
      controlling for age and baseline pain, CPM predicted EIH (model adjusted R =
      0.23, P = 0.007). CONCLUSIONS: CPM was attenuated in older adults, as measured
      with a noxious pressure stimulus after a thermal conditioning stimulus, and
      adults with greater CPM were more likely to report greater EIH.

PMID- 24870572
TI  - Dose-response relation between exercise duration and cognition.
AB  - PURPOSE: The study aimed to provide evidence-based recommendations for the
      prescription of a single session of exercise to improve cognitive performance. In
      particular, the purpose was to determine the dose-response relation between
      exercise duration and cognitive performance for a moderate-intensity session of
      aerobic exercise. METHODS: Twenty-six healthy young men participated in a reading
      control treatment and three exercise treatments presented in a random order. The
      exercise treatments were designed on the basis of the American College of Sports
      Medicine guidelines and consisted of a 5-min warm-up, a 5-min cooldown, and
      cycling at moderate intensity (approximately 65% HR reserve) for 10, 20, or 45
      min. The Stroop test was administrated after completion of each assigned
      treatment. RESULTS: Exercise at moderate intensity for 20 min resulted in
      significantly better cognitive performance, as assessed by shorter response time
      and higher accuracy. This result was found regardless of the type of cognitive
      function assessed. In addition, a curvilinear dose-response relation between
      exercise duration and cognitive performance was observed. CONCLUSIONS: An
      exercise session consisting of a 5-min warm-up, 20 min of moderate-intensity
      exercise, and a 5-min cooldown improves cognition, whereas shorter or longer
      durations of moderate exercise have negligible benefits. This study provides the
      foundation for the prescription of a single session of moderate exercise to
      facilitate cognitive function in healthy younger adults.

PMID- 24870573
TI  - Association of y balance test reach asymmetry and injury in division I athletes.
AB  - PURPOSE: The Y balance test (YBT) is a screen of dynamic balance requiring stance
      leg balance while the contralateral leg reaches in anterior (ANT), posteromedial
      (PM), and posterolateral (PL) directions. YBT has been proposed as a screen for
      injury risk; however, limited research has examined the association between YBT
      and injury. The purpose of this study was to examine the association between YBT
      (asymmetry and composite score (CS)) and noncontact injury in a sample of
      Division I (DI) college athletes from multiple sports. METHODS: DI college
      athletes were screened with the YBT during the preparticipation examination to
      determine asymmetry (absolute difference between legs in ANT, PL, and PM) and CS
      (summed average of right/left ANT, PL, and PM normalized to leg length).
      Participants were followed throughout the sport season, and noncontact injuries
      requiring athletic training staff intervention were recorded for analysis.
      Demographic variables between injured and uninjured athletes were assessed with
      independent t-tests. Receiver operating characteristic (ROC) curves determined
      optimal cut points for predicting injury on the basis of CS and asymmetry. CS was
      analyzed as a continuous variable, as ROC curves were unable to maximize
      sensitivity and specificity. Logistic regression models adjusted for sport and
      previous injury determined the odds of injury on the basis of asymmetry and CS.
      RESULTS: One hundred and eighty-four participants were included in analysis; 81
      were injured. ROC curves determined asymmetry >4 cm (sensitivity, 59%;
      specificity, 72%) as the optimal cut point for predicting injury. Only ANT
      asymmetry was significantly associated with noncontact injury (odds ratio, 2.33;
      95% confidence interval, 1.15-4.76). CONCLUSIONS: ANT asymmetry >4 cm was
      associated with increased risk of noncontact injury. CS in this sample of DI
      athletes was not associated with increased risk of injury.

PMID- 24870574
TI  - Protein ingestion increases myofibrillar protein synthesis after concurrent
      exercise.
AB  - PURPOSE: We determined the effect of protein supplementation on anabolic
      signaling and rates of myofibrillar and mitochondrial protein synthesis after a
      single bout of concurrent training. METHODS: Using a randomized crossover design,
      eight healthy males were assigned to experimental trials consisting of resistance
      exercise (8 * 5 leg extension, 80% 1RM) followed by cycling (30 min at
      approximately 70% VO2peak) with either postexercise protein (PRO, 25-g whey
      protein) or placebo (PLA) ingestion. Muscle biopsies were obtained at rest and at
      1 and 4 h after exercise. RESULTS: Akt and mTOR phosphorylation increased 1 h
      after exercise with PRO (175%-400%, P < 0.01) and was different from PLA (150%
      300%, P < 0.001). Muscle RING finger 1 and atrogin-1 messenger RNA (mRNA) were
      elevated after exercise but were higher with PLA compared with those in PRO at 1
      h (50%-315%, P < 0.05), whereas peroxisome proliferator-activated receptor gamma
      coactivator 1-alpha mRNA increased 4 h after exercise (620%-730%, P < 0.001),
      with no difference between treatments. Postexercise rates of myofibrillar protein
      synthesis increased above rest in both trials (75%-145%, P < 0.05) but were
      higher with PRO (67%, P < 0.05), whereas mitochondrial protein synthesis did not
      change from baseline. CONCLUSIONS: Our results show that a concurrent training
      session promotes anabolic adaptive responses and increases metabolic/oxidative
      mRNA expression in the skeletal muscle. PRO ingestion after combined resistance
      and endurance exercise enhances myofibrillar protein synthesis and attenuates
      markers of muscle catabolism and thus is likely an important nutritional strategy
      to enhance adaptation responses with concurrent training.

PMID- 24870575
TI  - Effects of exercise in the cold on Ghrelin, PYY, and food intake in overweight
      adults.
AB  - PURPOSE: Exercise in cold water has been shown to simulate postexercise energy
      intake (EI) in normal-weight individuals. However, the effect of cold exercise on
      EI in overweight individuals has yet to be examined. The present study
      investigated the effect of brisk walking in a cold (8 degrees C) and neutral (20
      degrees C) environment on postexercise EI and appetite hormone responses.
      METHODS: Sixteen overweight participants (10 men and six women; age, 50.1 +/-
      11.6 yr; body mass index, 28.9 +/- 4.2 kg.m) completed a 45-min treadmill walk at
      8 degrees C and 20 degrees C in a randomized counterbalanced design. Participants
      were presented with an ad libitum buffet meal 45 min after exercise, and EI was
      covertly measured. Skin and rectal temperature were monitored throughout exercise
      and for 30 min after exercise, and concentrations of the appetite hormones total
      ghrelin, acylated ghrelin, and total peptide YY were assessed before and after
      exercise and before and after meal. RESULTS: EI was significantly greater after
      exercise in the cold (1299 +/- 657 kcal (mean +/- SD)) compared with that after
      exercise in the neutral environment (1172 +/- 537 kcal (mean +/- SD)) (P < 0.05).
      The change in the acylated ghrelin concentrations and the acylated ghrelin AUC
      values were significantly greater during walking in the cold versus those during
      walking in the neutral condition (P < 0.05). CONCLUSIONS: These findings show
      that in overweight individuals, exercise in the cold stimulates postexercise EI
      to a greater extent than exercise in a neutral environment.

PMID- 24870576
TI  - Heterogeneity of muscle damage induced by electrostimulation: a multimodal MRI
      study.
AB  - PURPOSE: Neuromuscular electrostimulation (NMES) leads to a spatially fixed,
      synchronous, and superficial motor unit recruitment, which could induce muscle
      damage. Therefore, the extent of muscle damage and its spatial occurrence were
      expected to be heterogeneous across and along the quadriceps femoris (QF)
      muscles. The aim of the present study was to characterize muscle spatial
      heterogeneity in QF damage after a single bout of isometric NMES using multimodal
      magnetic resonance imaging (MRI). METHODS: Twenty-five young healthy males
      participated in this study. MRI investigations consisted of the assessment of
      muscle volume, transverse relaxation time (T2), and diffusion tensor imaging
      (DTI) in muscles positioned near the stimulation electrodes (i.e., vastus
      lateralis (VL) and vastus medialis (VM)) and muscles located outside the
      stimulated regions (i.e., vastus intermedius and rectus femoris). These
      measurements were performed 6 d before, and 2 d and 4 d (D4) after the NMES
      session. RESULTS: For the muscles placed in direct contact with the stimulation
      electrodes, volume (VL, +8.5%; VM, +3.8%), T2 (VL, +19.5%; VM, +6.7%) and radial
      diffusivity (lambda3) (VL, + 7.3%; VM, +3.7%) significantly increased at D4.
      Whereas MRI parameter changes were larger for VL as compared with those for other
      QF muscles at D4, homogeneous alterations were found along all QF muscles.
      CONCLUSIONS: Isometric NMES induced specific and localized alterations in VL and
      VM, with heterogeneous damage amplitude among them. Potential effects of
      unaccustomed intermuscle shear stress during electrically evoked isometric
      contractions could be a key factor in the spatial occurrence and the extent of
      damage among QF muscles (especially in VL). The kinetics and extent of MRI
      changes varied between T2 and diffusion tensor imaging metrics, suggesting the
      involvement of different physiological processes.

PMID- 24870577
TI  - Comparability of measured acceleration from accelerometry-based activity
      monitors.
AB  - BACKGROUND: Accelerometers that provide triaxial measured acceleration data are
      now available. However, equivalence of output between brands cannot be assumed
      and testing is necessary to determine whether features of the acceleration signal
      are interchangeable. PURPOSE: This study aimed to establish the equivalence of
      output between two brands of monitor in a laboratory and in a free-living
      environment. METHODS: For part 1, 38 adults performed nine laboratory-based
      activities while wearing an ActiGraph GT3X+ and GENEActiv (Gravity Estimator of
      Normal Everyday Activity) at the hip. For part 2, 58 children age 10-12 yr wore a
      GT3X+ and GENEActiv at the hip for 7 d in a free-living setting. RESULTS: For
      part 1, the magnitude of time domain features from the GENEActiv was greater than
      that from the GT3X+. However, frequency domain features compared well, with
      perfect agreement of the dominant frequency for 97%-100% of participants for most
      activities. For part 2, mean daily acceleration measured by the two brands was
      correlated (r = 0.93, P < 0.001, respectively) but the magnitude was
      approximately 15% lower for the GT3X+ than that for the GENEActiv at the hip.
      CONCLUSIONS: Frequency domain-based classification algorithms should be
      transferable between monitors, and it should be possible to apply time domain
      based classification algorithms developed for one device to the other by applying
      an affine conversion on the measured acceleration values. The strong relation
      between accelerations measured by the two brands suggests that habitual activity
      level and activity patterns assessed by the GENE and GT3X+ may compare well if
      analyzed appropriately.

PMID- 24870578
TI  - Leukocyte IGF-1 receptor expression during muscle recovery.
AB  - INTRODUCTION: The insulin-like growth factor 1 (IGF-1) system plays a central
      role in anabolic cellular processes. Recently, a regulatory role of IGF-1 in the
      immune response for muscle repair has been suggested, but how it modulates the
      inflammatory process is largely unknown. We evaluated changes in leukocyte
      expression of IGF-1 receptors (IGF-1R) during recovery from resistance exercise
      to determine whether changes in the potential for IGF-1 interactions with
      leukocytes may mediate the role of IGF-1 in muscle repair. METHODS: Twenty
      resistance-trained men (18-35 yr) performed resistance exercise followed by cold
      water immersion (CWI) or control treatment (CON) on three consecutive days. Blood
      was sampled at baseline (PRE), immediately (IP), 30 min (30P), 24 h (24H), and 48
      h after (48H) exercise. Circulating IGF-1 was assayed, and IGF-1 receptor
      expression (CD221) on gated circulating leukocytes (monocytes, granulocytes, and
      lymphocytes) was measured by flow cytometry. Time and treatment effects were
      analyzed with ANCOVA. RESULTS: Circulating IGF-1 significantly increased from PRE
      to IP as a result of resistance exercise, but no differences between CON and CWI
      were observed. Mean fluorescence intensity of CD221 on monocytes and granulocytes
      and percent of CD221+ granulocytes significantly increased at 30P (P < 0.000) and
      returned to preexercise levels by 24H. No treatment effects on monocytes or
      granulocytes were observed. On lymphocytes, mean fluorescence intensity of CD221+
      significantly increased from PRE to 30P in CWI. CONCLUSIONS: Changes in IGF-1 and
      its receptor on monocytes and granulocytes seem to be part of the mechanism that
      facilitates recovery from resistance exercise during earlier stages of muscle
      recovery. In addition, CWI seems to alter IGF-mediated responses on slower-acting
      lymphocytes, suggesting that its effects may be seen in later stages of muscle
      repair.

PMID- 24870579
TI  - Effects of age and long-term endurance training on VO2 kinetics.
AB  - PURPOSE: This study examined the effects of age and training status on the
      pulmonary oxygen uptake (VO2p) kinetics of untrained and chronically trained
      young, middle-age, and older groups of men. METHODS: Breath-by-breath VO2p and
      near-infrared spectroscopy-derived muscle deoxygenation ([HHb]) were monitored
      continuously in young (20-39 yr) trained (YT, n = 8) and untrained (YuT, n = 8),
      middle-age (40-59 yr) trained (MT, n = 9) and untrained (MuT, n = 9), and older
      (60-85 yr) trained (OT, n = 9) and untrained (OuT, n = 8) men. On-transient VO2p
      and [HHb] responses to cycling exercise at 80% of the estimated lactate threshold
      (three repeats) were modeled as monoexponential. Data were scaled to a relative
      percentage of the response (0%-100%), the signals time aligned, and the
      individual [HHb]-to-VO2p ratio was calculated as the average [HHb]/VO2 during the
      20- to 120-s period after exercise onset. RESULTS: The time constant for the
      adjustment of phase II pulmonary VO2 (tauVO2p) was larger in OuT (42.0 +/- 11.3
      s) compared with that in YT (17.0 +/- 7.5 s), MT (18.1 +/- 5.3 s), OT (19.8 +/-
      5.4 s), YuT (25.7 +/- 6.6 s), and MuT (24.4 +/- 7.4 s) (P < 0.05). Similarly, the
      [HHb]/VO2 ratio was larger than 1.0 in OuT (1.30 +/- 0.13, P < 0.05) and this
      value was larger than that observed in YT (1.01 +/- 0.07), MT (1.04 +/- 0.05), OT
      (1.04 +/- 0.04), YuT (1.05 +/- 0.03), and MuT (1.02 +/- 0.09) (P < 0.05).
      CONCLUSIONS: This study showed that the slower VO2kinetics typically observed in
      older individuals can be prevented by long-term endurance training interventions.
      Although the role of O2 delivery relative to peripheral use cannot be elucidated
      from the current measures, the absence of age-related slowing of VO2 kinetics
      seems to be partly related to a preservation of the matching of O2 delivery to O2
      utilization in chronically trained older individuals, as suggested by the
      reduction in the [HHb]/VO2 ratio.

PMID- 24870580
TI  - Effect of blood flow restriction on tissue oxygenation during knee extension.
AB  - PURPOSE: Time-resolved near-infrared spectroscopy was used to quantify tissue oxy
      and deoxyhemoglobin concentrations ([HbO2] and [HbR]) and O2 saturation (stO2)
      in the oblique fibers of the vastus medialis muscle and brain prefrontal cortex
      during knee extension with and without blood flow restriction (BFR). METHODS: Six
      young healthy males performed three sets of knee extensions on a dynamometer (50%
      one-repetition maximum) separated by 90-s rest periods in three conditions: 1)
      until fatigue without BFR (fatigue), 2) until fatigue with BFR (100 mm Hg cuff
      constriction around thigh (BFR)), 3) same number of repetitions from condition 2
      without BFR (matched). Each condition was performed on a separate visit. RESULTS:
      BFR was associated with higher [HbR] at the oblique fibers of the vastus medialis
      muscle (rest 1: 57.8 (BFR) vs 35.0 MUM (matched); P < 0.0001) and a significantly
      lower stO2 during recovery periods between sets (7.5%-11.2 % lower than non-BFR
      conditions for rest 1 and 2, P < 0.0001). Using a piecewise linear spline method,
      a spike in [HbR] was observed before the onset of HbR clearance during recovery,
      causing HbR clearance to begin at a higher concentration (81 (BFR) vs 62 MUM
      (matched), P = 0.029). [HbO2] kinetics during recovery were also affected by BFR,
      with longer duration (BFR, 51 s; matched, 31 s; P = 0.047) but lower rate of
      increase (BFR, 58 MUM.min; matched, 89 MUM.min; P = 0.004) during recovery. In
      the prefrontal cortex, BFR was associated with increased [HbR], diminished
      increase in [HbO2], and higher subjective exertion. CONCLUSIONS: These findings
      yield insight into possible physiological mechanisms of BFR and suggest a role of
      time-resolved near-infrared spectroscopy in monitoring and optimization of BFR
      exercise on an individual basis.

PMID- 24870581
TI  - Physical fitness and depressive symptoms during army basic combat training.
AB  - INTRODUCTION: Mental health-related problems are a significant cause of attrition
      during basic combat training (BCT). Evidence in civilian populations suggests
      that physical fitness is associated with psychological benefits in civilians, but
      little is known about the association between physical fitness and psychological
      adjustment during BCT. METHODS: This study prospectively examined the association
      between physical fitness and depressive symptoms in 300 BCT soldiers from May to
      July 2012 at Fort Jackson, Columbia, SC. Soldiers completed a baseline Army
      Physical Fitness Test (APFT) and survey within 1 wk of arriving at BCT and an end
      of-cycle survey after 8 wk of BCT. Soldiers were assigned to the "high" fitness
      category if they had a passing score on the standard APFT of greater than or
      equal to 180 out of 300 points. Soldiers scoring less than 180 points on the APFT
      were assigned to the "low" fitness category. Depressive symptoms were measured
      using the 20-item Center for Epidemiologic Studies Depression scale. RESULTS: In
      multivariate analyses, adjusting for baseline demographics, self-reported sleep
      before BCT, BCT confidence, Army identification, and depressive symptoms, the
      odds of reporting depressive symptoms were 60% lower for soldiers in the high
      fitness category (odds ratio, 0.40; 95% confidence interval, 0.19-0.84) compared
      with soldiers in the low fitness category. CONCLUSIONS: Analogous to other
      positive outcomes of soldier fitness, improvement of soldier physical fitness
      before BCT might improve soldiers' psychological health outcomes.

PMID- 24870582
TI  - Tibialis anterior moment arm: effects of measurement errors and assumptions.
AB  - Accurate estimates of tibialis anterior (TA) muscle force are important in many
      contexts. Two approaches commonly used to estimate moment arms are the tendon
      excursion (TE) and geometric (GEO) methods. Previous studies report poor
      agreement between the two approaches. PURPOSE: The purposes of this study were to
      1) assess the effect of methodological variations in the two methods of moment
      arm estimation and 2) determine how these variations affect agreement between the
      methods. METHODS: TA moment arms were determined using TE and GEO. Errors
      associated with tendon stretch/hysteresis, talus rotation relative to the foot,
      and the location of the line of action were investigated. RESULTS: For TE, large
      errors in moment arm estimates across the range of motion were found when tendon
      length changes (P = 0.001) were not corrected for. For GEO, the estimated moment
      arm was reduced at an ankle angle of -15 degrees  when discrepancies between
      talus and foot rotations were accounted for or when an alternative tendon line of
      action was used either separately (effect size (ES), 0.46 and 0.58, respectively;
      P > 0.05) or together (ES, 0.89; P > 0.05). TE-derived moment arms were smaller
      than GEO-derived moment arms (ES, 0.68-4.86, varying by angle) before accounting
      for sources of error. However, these differences decreased after error correction
      (ES, 0.09-1.20, P > 0.05). Nonetheless, the shape of the moment arm-joint angle
      relation was curvilinear for TE but linear for GEO. CONCLUSIONS: Of all
      methodological modifications, accounting for tendon length changes had the
      largest effect on TA moment arm estimates. We conclude that the TE method is
      viable to determine TA moment arms as long as changes in tendon length are
      accounted for.

PMID- 24870583
TI  - Evaluation of ActiGraph's low-frequency filter in laboratory and free-living
      environments.
AB  - The ActiGraph (AG) is the most commonly used research-grade physical activity
      monitor. Although several investigators have examined the effects of the "low
      frequency extension" (LFE) on step counts in the free-living environment, a
      direct comparison with a valid criterion method is lacking. We sought to
      determine the accuracy of the AG's LFE to measure step counts during laboratory
      and free-living activities in two versions of the device (GT1M and GT3X).
      METHODS: Twenty-four participants wore the StepWatch 3 and two versions of the
      AG, with the LFE turned on (GT1M-LFE and GT3X-LFE) and the LFE turned off (GT1M-N
      and GT3X-N), on different days. Direct observation of steps and the ankle-worn
      StepWatch 3 served as the criterion methods for the treadmill and free-living
      condition, respectively. All statistical analyses were performed on the percent
      difference between the devices as [(measured - actual)/actual]. RESULTS: During
      treadmill walking, the GT1M-N and GT3X-N underestimated steps by approximately
      60% at 40 m.min (P < 0.001) and by 31% at 54 m.min (P < 0.001). With the LFE
      turned on, this underestimation was reduced to 7% and 4% for the GT1M and GT3X,
      respectively. Under free-living conditions, both the GT1M-LFE and GT3X-LFE
      overestimated steps by approximately 32% (P < 0.001) whereas the GT1M-N and GT3X
      N steps were underestimated by 30% and 25%, respectively (P < 0.001).
      CONCLUSIONS: Turning the LFE on lessens the underestimation of steps recorded at
      walking speeds <=54 m.min for both the GT3X and GT1M. However, the increased
      sensitivity provided by the AG's LFE results in overestimation of steps taken
      throughout the day, when compared with the criterion device. Meanwhile, failure
      to turn the LFE on results in an underestimation of steps taken throughout the
      day.

PMID- 24870584
TI  - Bone mineral density across a range of physical activity volumes: NHANES 2007
      2010.
AB  - INTRODUCTION: The association between aerobic physical activity volume and bone
      mineral density (BMD) is not completely understood. The purpose of this study was
      to clarify the association between BMD and aerobic activity across a broad range
      of activity volumes, particularly volumes between those recommended in the 2008
      Physical Activity Guidelines for Americans and those of trained endurance
      athletes. METHODS: Data from the 2007-2010 National Health and Nutrition
      Examination Survey were used to quantify the association between reported
      physical activity and BMD at the lumbar spine and proximal femur across the
      entire range of activity volumes reported by US adults. Participants were
      categorized into multiples of the minimum guideline-recommended volume based on
      reported moderate- and vigorous-intensity leisure activity. Lumbar and proximal
      femur BMD were assessed with dual-energy x-ray absorptiometry. RESULTS: Among
      women, multivariable-adjusted linear regression analyses revealed no significant
      differences in lumbar BMD across activity categories, whereas proximal femur BMD
      was significantly higher among those who exceeded the guidelines by 2-4 times
      than those who reported no activity. Among men, multivariable-adjusted BMD at
      both sites neared its highest values among those who exceeded the guidelines by
      at least 4 times and was not progressively higher with additional activity.
      Logistic regression estimating the odds of low BMD generally echoed the linear
      regression results. CONCLUSIONS: The association between physical activity volume
      and BMD is complex. Among women, exceeding guidelines by 2-4 times may be
      important for maximizing BMD at the proximal femur, whereas among men, exceeding
      guidelines by >=4 times may be beneficial for lumbar and proximal femur BMD.

PMID- 24870585
TI  - Whole-body heat exchange during heat acclimation and its decay.
AB  - PURPOSE: The purpose of this study was to quantify how much whole-body heat loss
      increases during heat acclimation and the decay in these improvements after heat
      acclimation. METHODS: Ten males underwent a 14-d heat acclimation protocol that
      consisted of 90 min of cycling in the heat (40 degrees C, 20% relative humidity)
      at approximately 50% of maximum oxygen consumption. Before (day 0), during (day
      7), and at the end (day 14) of the heat acclimation protocol as well as 7 and 14
      d after heat acclimation (days 21 and 28), whole-body heat exchange (evaporative
      and dry) was measured using direct calorimetry during three bouts of 30-min
      exercise at 300 (Ex1), 350 (Ex2), and 400 W.m (Ex3), each separated by 10 and 20
      min of recovery, respectively, at 35 degrees C and 16% relative humidity.
      Concurrent measurements of metabolic heat production (indirect calorimetry)
      allowed for the direct calculation of change in body heat content (DeltaHb).
      RESULTS: After accounting for an increase in net dry heat gain, increases in
      whole-body evaporative heat loss were evident for Ex2 and Ex3 on day 7 (Ex2, 4.9
      +/- 5.6%; Ex3, 9.0 +/- 6.0%; both P <= 0.05) and all heat loads on day 14 (Ex1,
      7.6 +/- 8.3%; Ex2, 7.7 +/- 5.5%; Ex3, 11.2 +/- 4.6%; all P <= 0.05) relative to
      day 0 (Ex1, 494 +/- 27 W; Ex2, 583 +/- 21 W; Ex3, 622 +/- 36 W). As a result, a
      lower cumulative DeltaHb was measured on day 7 (-18 +/- 8%, P <= 0.001) and day
      14 (-26 +/- 10%, P <= 0.001) compared with that measured on day 0 (1062 +/- 123
      kJ). Most of these improvements were retained after 2 wk of nonexposure to the
      heat. CONCLUSIONS: This is the first study to quantify how much 14 d of heat
      acclimation can increase whole-body evaporative heat loss, which can improve by
      as much as approximately 11%.

PMID- 24870586
TI  - Functional Analysis of KIF3A and KIF3B during Spermiogenesis of Chinese Mitten
      Crab Eriocheir sinensis.
AB  - BACKGROUND: Spermatogenesis represents the transformation process at the level of
      cellular development. KIF3A and KIF3B are believed to play some roles in the
      assembly and maintenance of flagella, intracellular transport of materials
      including organelles and proteins, and other unknown functions during this
      process. During spermatogenesis in Eriocheir sinensis, if the sperm shaping
      machinery is dependent on KIF3A and KIF3B remains unknown. METHODOLOGY/PRINCIPAL
      FINDINGS: The cDNA of KIF3A and KIF3B were obtained by designing degenerate
      primers, 3'RACE, and 5'RACE. We detected the genetic presence of kif3a and kif3b
      in the heart, muscle, liver, gill, and testis of E. sinensis through RT-PCR. By
      western blot analysis, the protein presence of KIF3A and KIF3B in heart, muscle,
      gill, and testis reflected the content in protein level. Using in situ
      hybridization and immunofluorescence, we could track the dynamic location of
      KIF3A and KIF3B during different developmental phases of sperm. KIF3A and KIF3B
      were found surrounding the nucleus in early spermatids. In intermediate
      spermatids, these proteins expressed at high levels around the nucleus and
      extended to the final phase. During the nuclear shaping period, KIF3A and KIF3B
      reached their maximum in the late spermatids and were located around the nucleus
      and concentrated in the acrosome to some extent. CONCLUSIONS/SIGNIFICANCE: Our
      results revealed that KIF3A and KIF3B were involved in the nuclear and cellular
      morphogenesis at the levels of mRNA and protein. These proteins can potentially
      facilitate the intracellular transport of organelles, proteins, and other
      cargoes. The results represent the functions of KIF3A and KIF3B in the
      spermatogenesis of Crustacea and clarify phylogenetic relationships among the
      Decapoda.

PMID- 24870587
TI  - Ethanolic extract of Astragali radix and Salviae radix prohibits oxidative brain
      injury by psycho-emotional stress in whisker removal rat model.
AB  - Myelophil, an ethanolic extract of Astragali Radix and Salviae Radix, has been
      clinically used to treat chronic fatigue and stress related disorders in South
      Korea. In this study, we investigated the protective effects of Myelophil on a
      whisker removal-induced psycho-emotional stress model. SD rats were subjected to
      whisker removal after oral administration of Myelophil or ascorbic acid for
      consecutive 4 days. Whisker removal considerably increased total reactive oxygen
      species in serum levels as well as cerebral cortex and hippocampal regions in
      brain tissues. Lipidperoxidation levels were also increased in the cerebral
      cortex, hippocampus regions, and brain tissue injuries as shown in histopathology
      and immunohistochemistry. However, Myelophil significantly ameliorated these
      alterations, and depletion of glutathione contents in both cerebral cortex and
      hippocampus regions respectively. Serum levels of corticosterone and adrenaline
      were notably altered after whisker removal stress, whereas these abnormalities
      were significantly normalized by pre-treatment with Myelophil. The NF-kappaB was
      notably activated in both cerebral cortex and hippocampus after whisker removal
      stress, while it was efficiently blocked by pre-treatment with Myelophil.
      Myelophil also significantly normalizes alterations of tumor necrosis factor
      alpha, interleukin (IL)-1beta, IL-6 and interferon-gamma in both gene expressions
      and protein levels. These results suggest that Myelophil has protective effects
      on brain damages in psycho-emotional stress, and the underlying mechanisms
      involve regulation of inflammatory proteins, especially NF-kappaB modulation. 

PMID- 24870588
TI  - Intravenous immunoglobulin preparation prevents the production of pro
      inflammatory cytokines by modulating NFkappaB and MAPKs pathways in the human
      monocytic THP-1 cells stimulated with procalcitonin.
AB  - OBJECTIVE: In the previous investigations, we showed that intravenous
      immunoglobulin (IVIG) prevented cytokine release in procalcitonin (PCT)
      stimulated monocytic cells. The aim of the present study was to investigate the
      underlying mechanisms of inhibition of IVIG on cytokine production in PCT
      stimulated THP-1 cells. METHODS: THP-1 cells treated with phorbol myristate
      acetate were stimulated with PCT. The protein levels of pro-inflammatory
      cytokines [tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and
      high-mobility group box 1 (HMGB1)] in the culture supernatants were determined
      using enzyme-linked immunosorbent assay kits. The mRNA level of TNF-alpha was
      determined by reverse transcription-polymerase chain reaction. The
      phosphorylations of nuclear factor kappa B (NFkappaB) and the mitogen-activated
      protein kinases (MAPKs) were determined by Western blotting. RESULTS: IVIG
      reduced mRNA expression and protein production of TNF-alpha in PCT-stimulated THP
      1 cells. Not only IVIG but also both the Fc fragment and the F(ab')2 fragment
      inhibited PCT-induced TNF-alpha, IL-6, and HMGB1 production. Furthermore, IVIG
      and its fragments suppressed PCT-induced phosphorylations of NFkappaB, p38 MAPK,
      and c-Jun N-terminal kinase. CONCLUSIONS: Our results indicate that IVIG prevents
      PCT-induced cytokine production mediated by not only the Fab region but also the
      Fc region. The activity of IVIG and its fragments might be regulated by
      inhibiting NFkappaB and MAPKs pathways in THP-1 cells.

PMID- 24870589
TI  - A Model for Art Therapy-Based Supervision for End-of-Life Care Workers in Hong
      Kong.
AB  - End-of-life care workers and volunteers are particularly prone to burnout given
      the intense emotional and existential nature of their work. Supervision is one
      important way to provide adequate support that focuses on both professional and
      personal competencies. The inclusion of art therapy principles and practices
      within supervision further creates a dynamic platform for sustained self
      reflection. A 6-week art therapy-based supervision group provided opportunities
      for developing emotional awareness, recognizing professional strengths, securing
      collegial relationships, and reflecting on death-related memories. The structure,
      rationale, and feedback are discussed. 

PMID- 24870590
TI  - Modeling of photoactive conjugated donor-acceptor copolymers: the effect of the
      exact HF exchange in DFT functionals on geometries and gap energies of oligomer
      and periodic models.
AB  - Conjugated copolymers with an alternating donor-acceptor (D-A) architecture are
      exploited as low-bandgap and high-hole-mobility materials in organic electronics.
      However, several of the presently available modeling methods predict different
      geometries and electronic properties for the same copolymer. In this work, the
      effect of the amount of exact Hartree-Fock (HF) exchange in density functionals
      on the planarity of the geometry and the electronic properties of the single
      oligomer chains of one benzodithiophene- and benzotriazole-based donor-acceptor
      copolymer and two fluorene-, thiophene-, and benzotriazole-based donor-acceptor
      copolymers is assessed. The functionals are B3LYP, PBE, PBE0, HSE06, LC-omegaPBE,
      omegaB97XD, M06, M06L, M062X, M06HF, and the optimally tuned OT-omegaB97X.
      Benchmarking of the methods is useful for understanding the results of a
      particular functional and allows, to a certain degree, comparison between results
      obtained with different functionals. Additionally, the applicability of the one
      dimensional periodic boundary condition (PBC) for modeling the D-A copolymers
      with long constitutional repeating units (CRUs) is evaluated. 

PMID- 24870591
TI  - Elevated expression of Cripto-1 correlates with poor prognosis in non-small cell
      lung cancer.
AB  - Human Cripto-1 (CR-1) plays an important oncogenic role during tumorigenesis and
      is overexpressed in a wide range of carcinomas, yet little is known about CR-1 in
      non-small cell lung cancer (NSCLC). The aims of this study were to detect CR-1
      expression in NSCLC and to analyze its association with prognosis of NSCLC
      patients. The expression of CR-1 messenger RNA (mRNA) and protein in 35 cases of
      NSCLC and corresponding noncancerous tissue samples was examined by quantitative
      real-time reverse transcription-polymerase chain reaction (qRT-PCR) and Western
      blotting. Immunohistochemistry was performed to detect the expression of CR-1 in
      128 NSCLC tissues. The expression levels of CR-1 mRNA and protein in NSCLC
      tissues were significantly higher than those in corresponding noncancerous
      tissues (P < 0.001). A high level of CR-1 expression was correlated with poor
      tumor differentiation (P = 0.002), tumor-node-metastasis (TNM) stage (P = 0.004),
      and lymph node metastasis (P = 0.001). The results of the Kaplan-Meier analysis
      indicated that a high expression level of CR-1 resulted in a significantly poor
      prognosis of NSCLC patients. Multivariate Cox regression analysis revealed that
      CR-1 expression level was an independent prognostic parameter for the overall
      survival rate of NSCLC patients. Our data suggest that the high expression of CR
      1 may play an important role in the progression of NSCLC, and CR-1 expression may
      offer a valuable marker for predicting the outcome of patients with NSCLC.

PMID- 24870592
TI  - The association between CD14-260C/T polymorphism and malignant tumor risk: a meta
      analysis of 5,603 participants.
AB  - The CD14-260C/T polymorphism has been implicated to be in association with
      malignant tumor. However, a number of studies have reported inconclusive results.
      The aim of this study was to investigate the relationship of CD14-260C/T
      polymorphism and malignant tumor risk by meta-analysis. A search was performed in
      PubMed, Embase, the Chinese Journals Full-text Database (CNKI), and Wanfang
      databases up to August 2013. Odds ratio (OR) and 95 % confidence interval (95 %
      CI) were used to assess the association. Statistical analysis was calculated by
      STATA 11.0 software. The polymorphism was identified from 11 articles (12 case
      control studies), involving 2,660 cases and 2,943 controls. Overall, no
      significant association between CD14-260C/T polymorphism and malignant tumor risk
      was found in the dominant model (TT + TC vs. CC: OR = 0.86, 95 % CI = 0.67-1.11).
      In the subgroup analysis by malignant tumor types, we found that the heterozygote
      model (TC vs. CC) might reduce the risk of malignant tumor, especially
      hematological malignance and prostate cancer (OR = 0.67, 95 % CI = 0.47-0.95),
      but not associated with gastrointestinal cancer susceptibility. In the subgroup
      analysis by ethnicity, no significant associations were found among different
      ethnicities. The study suggested that CD14-260C/T polymorphism might be a
      protective factor for hematological malignance and prostate tumor susceptibility
      but not an independent risk factor for gastrointestinal cancer susceptibility. To
      further evaluate the association between the polymorphism and malignant tumor
      susceptibility, more studies involving thousands of patients are required.

PMID- 24870593
TI  - The programmed cell death 6 interacting protein insertion/deletion polymorphism
      is associated with non-small cell lung cancer risk in a Chinese Han population.
AB  - It has been proposed that genetic factors contribute to the susceptibility of non
      small cell lung cancer (NSCLC). The programmed cell death 6 interacting protein
      (PDCD6IP) encodes for a protein that has been known to bind to the products of
      the PDCD6 gene, a required protein in apoptosis. The aim of this study is to
      investigate the relationship between PDCD6IP insertion/deletion (I/D)
      polymorphism (rs28381975) and NSCLC risk in a Chinese population. A population
      based case-control study was conducted in 449 NSCLC patients and 512 cancer-free
      controls. The genotype of the PDCD6IP gene was determined by using a polymerase
      chain reaction assay. The promoter activity was analyzed by luciferase reporter
      assay in A549 and H1299 cells. Statistically significant difference was observed
      when the patients and controls were compared according to ID + II versus DD (OR =
      1.72, 95 % CI 1.29-2.31, P < 0.01). The I allele was significantly associated
      with NSCLC risk (OR = 1.41, 95 % CI 1.18-1.69, P < 0.01). Compared to TNM stage I
      + II, PDCD6IP I/D polymorphism significantly increased advanced NSCLC risk (OR =
      2.06, 95 % CI 1.30-3.26, P < 0.01). Promoter reporter structures carrying the I
      allele displayed significantly higher promoter activity than the D allele in A549
      and H1299 cells (P = 0.001). The results from this study suggested that PDCD6IP
      I/D polymorphism was potentially related to NSCLC susceptibility in Chinese Han
      population.

PMID- 24870594
TI  - Increased MTHFD2 expression is associated with poor prognosis in breast cancer.
AB  - The aim of this study was to investigate the expression levels of
      methylenetetrahydrofolate dehydrogenase (NADP + -dependent) 2 (MTHFD2) and the
      associated clinical implications in breast cancer. MTHFD2 expression was measured
      by Western blot and immunohistochemistry in 698 tissue sections taken from breast
      cancer patients. The relationship between MTHFD2 expression, clinicopathological
      parameters, and the prognosis of breast cancer was subsequently determined. In
      comparison with para-carcinoma tissue specimens, an enhanced expression of MTHFD2
      was observed in breast cancer tissue specimens (P < 0.05). In total, 41.12 %
      (287/698) of breast cancer tissue specimens had high levels of MTHFD2. After
      universal and Spearman regression correlation analyses, MTHFD2 expression was
      found to correlate with tumor size, histological grade, lymph node metastasis,
      and distant metastases (P = 0.001, 0.002, 0.001, and 0.001, respectively).
      Furthermore, patients with MTHFD2-expressing tumors had a significantly poorer
      prognosis than those with no or low MTHFD2 expression. (P = 0.002). Using the Cox
      regression test, MTHFD2 was identified as an independent prognostic factor (P =
      0.001). MTHFD2 was differentially expressed in breast cancer tissue. Therefore,
      this protein may be an independent prognostic factor and a potential therapeutic
      target for future breast cancer treatments.

PMID- 24870595
TI  - The subsets of dendritic cells and memory T cells correspond to indoleamine 2,3
      dioxygenase in stomach tumor microenvironment.
AB  - The abnormal distributions of memory T cells (Tm) and dendritic cells (DC) in
      stomach cancer are not well understood. Indoleamine 2,3-dioxygenase (IDO),
      produced by DC, may be an important enzyme affecting function and proliferation
      of Tm. In this study, IDO expression was examined by immunohistochemical
      staining. The subsets of Tm and DC were counted by flow cytometry. The
      percentages of CD4 + Tm and CD4 + central Tm (Tcm) were lower in tumor tissues
      than in normal tissues (P < 0.05), while the CD4 + effector Tm (Tem) and CD8 +
      Tem percentages were higher in tumor tissues (P < 0.05). The ratio of myeloid DC
      (DC1)/plasmacytoid DC (DC2) was significantly lower in tumor tissues (P = 0.009).
      The high expression of IDO was more frequently observed in tumor tissues (P =
      0.001). The percentages of CD4 + Tm and CD8 + Tm were positively associated with
      DC1 percentage and ratio of DC1/DC2 (P < 0.05). The higher CD8 + Tcm percentage
      was associated with higher DC2 percentage (P = 0.025). The patients with high IDO
      expression had significantly lower CD4 + Tm (P = 0.012) and CD8 + Tm percentages
      (P = 0.033), but higher CD8 + Tem percentage (P < 0.01). Concerning on
      clinicopathologic features, the higher DC2 percentage was associated with larger
      tumor size (P = 0.019). The CD4 + Tm and CD8 + Tem percentages were significantly
      associated with clinical stage and lymph node metastasis; the high IDO
      expressions were significantly associated with deeper tumor invasion (P = 0.016)
      and lymph node metastasis (P = 0.038). Thus, DC subsets, Tm subsets, and IDO
      expression were correlated with each other. They were associated with the
      established clinicopathologic features, such as tumor size, depth of invasion,
      lymph node metastasis, and clinical stage.

PMID- 24870597
TI  - MicroRNA-520a-5p displays a therapeutic effect upon chronic myelogenous leukemia
      cells by targeting STAT3 and enhances the anticarcinogenic role of capsaicin.
AB  - Aberrant expression profiles of microRNAs (miRNAs) have been previously
      demonstrated for having essential roles in a wide range of cancer types including
      leukemia. Antiproliferative or proapoptotic effects of capsaicin have been
      reported in several cancers. We aimed to study miRNAs involved in the Janus
      kinase/signal transducers and activators of transcription (JAK/STAT) pathway in
      chronic myeloid leukemia cell model and the effects of the capsaicin treatment on
      cell proliferation and miRNA regulation. miR-520a-5p expression was extremely
      downregulated in capsaicin-treated cells. Repressing the level of miR-520a-5p by
      transient transfection with specific miRNA inhibitor oligonucleotides resulted in
      induced inhibition of proliferation in leukemic cells. According to
      bioinformatics analysis, STAT3 messenger RNA was predicted as a putative miR-520a
      5p target; which was confirmed by quantitative reverse transcriptase-polymerase
      chain reaction (qRT-PCR) and Western blot analysis. Cell proliferation inhibition
      was enhanced upon knockdown of STAT3 by RNA interference applications, but when
      miR-520a-5p inhibitor was additionally transfected onto STAT3 silenced cells,
      cell viability was dramatically decreased in leukemia cells. Finally, we observed
      the effects of capsaicin following miR-520a-5p inhibitor transfection upon cell
      proliferation, apoptosis, and STAT3 expression levels. We determined that,
      downregulation of miR-520a-5p affected the proliferation inhibition enhanced by
      capsaicin and reduced STAT3 mRNA and protein expression levels and increased
      apoptotic cell number. In summary, miR-520a-5p displays a therapeutic effect by
      targeting STAT3 and impacting the anticancer effects of capsaicin; whereas
      capsaicin, potentially through the miR-520a-5p/STAT3 interaction, induces
      apoptosis and inhibits K562 leukemic cell proliferation with need of further
      investigation.

PMID- 24870596
TI  - The prognostic value of ERCC1 expression in gastric cancer patients treated with
      platinum-based chemotherapy: a meta-analysis.
AB  - Numerous studies examined the association between excision repair complementation
      group 1 (ERCC1) expression and the prognosis of gastric cancer patients receiving
      platinum-based chemotherapy but yielded controversial results. We thus conducted
      a meta-analysis to quantitatively evaluate the prognostic value of ERCC1
      expression in gastric cancer patients receiving platinum-based chemotherapy. A
      systematic literature search was performed to identify relevant studies in
      PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge
      Infrastructure, Chinese Biomedical Literature Database, and WanFang Database up
      to December 17, 2013. Pooled hazard ratios (HRs) or odds ratios (ORs) with 95 %
      confidence intervals (CIs) were estimated. Moreover, meta-regression analysis and
      subgroup analysis were conducted according to ethnicity, HR extraction, detection
      methods, survival analysis, and quality score. A total of 1,409 patients from 21
      studies were subjected to final analysis. Positive/high ERCC1 expression was
      significantly associated with poorer overall survival (HR, 1.58; 95 % CI, 1.09
      2.28), especially in Asians (HR, 1.81; 95 % CI, 1.20-2.73), and lower response
      rate (OR, 0.26; 95 % CI, 0.18-0.36), but not with clinicopathological features,
      such as gender (OR, 1.01; 95 % CI, 0.68-1.51), grade (OR, 0.66; 95 % CI, 0.43
      1.01), and stage (OR, 1.05; 95 % CI, 0.58-1.90). This meta-analysis suggested
      that ERCC1 expression might be a useful biomarker to predict response and
      survival for gastric cancer patients receiving platinum-based chemotherapy,
      particularly in Asians.

PMID- 24870598
TI  - Melittin radiosensitizes esophageal squamous cell carcinoma with induction of
      apoptosis in vitro and in vivo.
AB  - Currently, unresectable esophageal squamous cell carcinoma (ESCC) is primarily
      treated by chemoradiotherapy. However, the outcome has not improved significantly
      because of radioresistance of cancer cells. This study aimed to determine the
      radiosensitizing effect of melittin, a novel component of bee venom, in ESCC.
      ESCC cell lines were irradiated with or without melittin. Cell proliferation was
      detected by Cell Counting Kit 8 assay. Radiosensitization was evaluated by
      clonogenic survival assay. Cell apoptosis was detected by flow cytometry. Results
      show that melittin potently sensitized ESCC cells to radiation with a
      sensitization enhancement ratio of 1.15-1.42. Radiosensitization was accompanied
      with enhanced apoptosis and regulated by apoptosis proteins. The results were
      confirmed by in vivo studies on tumor-bearing xenografts. In summary, these
      results provide support that melittin may be a potentially promising
      radiosensitizer in ESCC radiation therapy.

PMID- 24870599
TI  - Regulation of metastasis of pediatric multiple myeloma by MMP13.
AB  - The molecular mechanism underlying metastasis of pediatric multiple myeloma (MM)
      remains elusive. Here, we showed that the levels of MMP13 are significantly
      higher in MM from young patients than those from adult patients. Moreover, a
      strong correlation of the MMP13 and phosphorylated fibroblast growth factor
      receptor 4 (FGFR4) levels was detected in MM from young patients. To prove a
      causal link between activation of fibroblast growth factor receptors (FGFR)
      signaling pathway and MMP13 expression, we used a human MM line, RPMI-8226
      (8226), to study the underlying molecular basis. We found that FGF1-induced FGFR4
      phosphorylation in 8,226 cells resulted in significant activation of MMP13, and
      consequently, an increase in cancer invasiveness. FGFR4 inhibition in 8,226 cells
      abolished FGF1-stimulated MMP13 expression, suggesting that activation of FGFR
      signaling pathway in MM may promote cancer metastasis by inducing MMP13
      expression. To define the signaling cascades downstream of FGFR4 activation for
      MMP13 activation, we applied specific inhibitors for PI3K, Jun N-terminal kinase
      (JNK), and ERK/MAPK, respectively, to the FGF1-stimulated 8,226 cells. We found
      that only inhibition of ERK1/2 significantly decreased the activation of MMP13 in
      response to FGF stimulation, suggesting that activation of FGFR signaling may
      activate ERK/MAPK, rather than JNK or PI3K pathway to activate MMP13 expression
      in 8,226 cells. Our study thus highlights FGFR4 signaling pathway and MMP13 as
      novel therapeutic targets for MM.

PMID- 24870600
TI  - Selective laser sintered versus carbon fiber passive-dynamic ankle-foot orthoses:
      a comparison of patient walking performance.
AB  - Selective laser sintering (SLS) is a well-suited additive manufacturing technique
      for generating subject-specific passive-dynamic ankle-foot orthoses (PD-AFOs).
      However, the mechanical properties of SLS PD-AFOs may differ from those of
      commonly prescribed carbon fiber (CF) PD-AFOs. Therefore, the goal of this study
      was to determine if biomechanical measures during gait differ between CF and
      stiffness-matched SLS PD-AFOs. Subject-specific SLS PD-AFOs were manufactured for
      ten subjects with unilateral lower-limb impairments. Minimal differences in gait
      performance occurred when subjects used the SLS versus CF PD-AFOs. These results
      support the use of SLS PD-AFOs to study the effects of altering design
      characteristics on gait performance. 

PMID- 24870601
TI  - Clinical roundtable monograph: effective management of quality of life in
      metastatic breast cancer.
AB  - Quality of life is accepted as an important consideration in the management of
      patients with metastatic breast cancer, which remains incurable. Recent clinical
      trials of newer agents, such as eribulin and trastuzumab emtansine, have
      incorporated quality of life analyses. Quality of life is impacted by multiple
      patient-related, disease-related, and treatment-related factors. Therapies most
      beneficial for maintaining or improving quality of life include those that can
      effectively reduce tumor burden and tumor-related symptoms, but have toxicity
      profiles that are well tolerated and easily managed. Overall outcomes of patients
      with metastatic breast cancer improve when therapy is focused not only on the
      disease itself, but also on the goals of minimizing diseaserelated and treatment
      related symptoms. A paradigm shift now reflected in major guidelines is the
      incorporation of palliative care strategies earlier in the course of metastatic
      disease management. The selection and sequence of treatments should be made in
      cooperation with the patient and after consideration of her particular
      priorities.

PMID- 24870605
TI  - Silver-catalyzed decarboxylative acylfluorination of styrenes in aqueous media.
AB  - A mild catalytic decarboxylative acylfluorination of styrenes with alpha
      oxocarboxylic acids and Selectfluor is reported. This operationally simple and
      efficient method provides a fundamentally novel approach toward the synthesis of
      beta-fluorinated 3-aryl ketones with a wide range of substrate scope. 

PMID- 24870606
TI  - A flexible and inexpensive high-performance auditory evoked response recording
      system appropriate for research purposes.
AB  - Recording auditory evoked responses (AER) is done not only in hospitals and
      clinics worldwide to detect hearing impairments and estimate hearing thresholds,
      but also in research centers to understand and model the mechanisms involved in
      the process of hearing. This paper describes a high-performance, flexible, and
      inexpensive AER recording system. A full description of the hardware and software
      modules that compose the AER recording system is provided. The performance of
      this system was evaluated by conducting five experiments with both real and
      artificially synthesized auditory brainstem response and middle latency response
      signals at different intensity levels and stimulation rates. The results indicate
      that the flexibility of the described system is appropriate to record AER signals
      under several recording conditions. The AER recording system described in this
      article is a flexible and inexpensive high-performance AER recording system. This
      recording system also incorporates a platform through which users are allowed to
      implement advanced signal processing methods. Moreover, its manufacturing cost is
      significantly lower than that of other commercially available alternatives. These
      advantages may prove useful in many research applications in audiology.

PMID- 24870607
TI  - Amyloid beta in hereditary cerebral hemorrhage with amyloidosis-Dutch type.
AB  - Hereditary cerebral hemorrhage with amyloidosis - Dutch type is an autosomal
      dominant hereditary disease caused by a point mutation in the amyloid precursor
      protein gene on chromosome 21. The mutation causes an amino acid substitution at
      codon 693 (E22Q), the 'Dutch mutation'. Amyloid beta, the product after cleavage
      of the amyloid precursor protein, is secreted into the extracellular space. The
      Dutch mutation leads to altered amyloid beta cleavage and secretion, enhanced
      aggregation properties, higher proteolysis resistance, lowered brain efflux
      transporter affinity, and enhanced cell surfaces binding. All these result in
      amyloid beta accumulation in cerebral vessel walls, causing cell death and vessel
      wall integrity loss, making cerebral vessel walls in hereditary cerebral
      hemorrhage with amyloidosis-Dutch type more prone to rupture and obstruction,
      leading to hemorrhages and infarcts. Studying the effects of altered amyloid beta
      metabolism due to mutations like the 'Dutch' provides us with a better
      understanding of amyloid beta toxicity, also in other amyloid beta diseases like
      sporadic cerebral amyloid angiopathy and Alzheimer's disease.

PMID- 24870608
TI  - Effect of selective cyclooxygenase-2 inhibitor lumiracoxib on
      phenolsulfonphthalein disposition in rats.
AB  - Selective cyclooxygenase-2 inhibitor lumiracoxib was shown to have the strong
      inhibitory potencies on the renal organic anion transporter (OAT)1 and also on
      OAT3 from drug transport experiments. The purpose of this study was to examine
      the effect of lumiracoxib on disposition of phenolsulfonphthalein (PSP) - which
      is mainly excreted into urine via OATs - from in vivo experiments. After the
      intravenous injection of PSP and lumiracoxib into rats, pharmacokinetic analysis
      was performed. After the intravenous injection of PSP as a bolus, its plasma
      concentration decreased time-dependently. Until 60 min after the injection, 51.1%
      of the dose was recovered into urine. The simultaneous administration of
      lumiracoxib increased the plasma levels of PSP and reduced its urinary recovery
      to 23.6% of the dose. The pharmacokinetic analysis using a two-compartment model
      exhibited that lumiracoxib affected the parameters implying the elimination of
      PSP. The present study demonstrates that lumiracoxib interfered with urinary
      excretion of PSP in rats.

PMID- 24870609
TI  - Biochemical markers in early diagnosis and management of systemic amyloidoses.
AB  - Systemic amyloid diseases are characterized by widespread protein deposition as
      amyloid fibrils. Precise diagnostic framing is the prerequisite for a correct
      management of patients. This complex process is achieved through a series of
      steps, which include detection of the tissue amyloid deposits, identification of
      the amyloid type, demonstration of the amyloidogenic precursor, and evaluation of
      organ dysfunction/damage. Laboratory medicine plays a central role in the
      diagnosis and management of systemic amyloidoses, through the quantification of
      the amyloidogenic precursor and evaluation of end-organ damage using biomarkers.

PMID- 24870612
TI  - Iodocyclization of ethoxyethyl ethers to ynamides: an immediate construction to
      benzo[b]furans.
AB  - The iodocyclization of ethoxyethyl ethers to ynamides was completed within three
      seconds. The corresponding benzo[b]furans were obtained in high yields (84%
      quant.) under mild conditions. 

PMID- 24870611
TI  - Meek males and fighting females: sexually-dimorphic antipredator behavior and
      locomotor performance is explained by morphology in bark scorpions (Centruroides
      vittatus).
AB  - Sexual dimorphism can result from sexual or ecological selective pressures, but
      the importance of alternative reproductive roles and trait compensation in
      generating phenotypic differences between the sexes is poorly understood. We
      evaluated morphological and behavioral sexual dimorphism in striped bark
      scorpions (Centruroides vittatus). We propose that reproductive roles have driven
      sexually dimorphic body mass in this species which produces sex differences in
      locomotor performance. Poor locomotor performance in the females (due to the
      burden of being gravid) favors compensatory aggression as part of an alternative
      defensive strategy, while male morphology is coadapted to support a sprinting
      based defensive strategy. We tested the effects of sex and morphology on stinging
      and sprinting performance and characterized overall differences between the sexes
      in aggressiveness towards simulated threats. Greater body mass was associated
      with higher sting rates and slower sprinting within sexes, which explained the
      greater aggression of females (the heavier sex) and, along with longer legs in
      males, the improved sprint performance in males. These findings suggest females
      are aggressive to compensate for locomotor costs of reproduction while males
      possess longer legs to enhance sprinting for predator evasion and mate finding.
      Sexual dimorphism in the metasoma ("tail") was unrelated to stinging and
      sprinting performance and may best be explained by sexual selection. 

PMID- 24870613
TI  - Nanoplasmon-enabled macroscopic thermal management.
AB  - In numerous applications of energy harvesting via transformation of light into
      heat the focus recently shifted towards highly absorptive nanoplasmonic
      materials. It is currently established that noble metals-based absorptive
      plasmonic platforms deliver significant light-capturing capability and can be
      viewed as super-absorbers of optical radiation. Naturally, approaches to the
      direct experimental probing of macroscopic temperature increase resulting from
      these absorbers are welcomed. Here we derive a general quantitative method of
      characterizing heat-generating properties of optically absorptive layers via
      macroscopic thermal imaging. We further monitor macroscopic areas that are
      homogeneously heated by several degrees with nanostructures that occupy a mere 8%
      of the surface, leaving it essentially transparent and evidencing significant
      heat generation capability of nanoplasmon-enabled light capture. This has a
      direct bearing to a large number of applications where thermal management is
      crucial. 

PMID- 24870615
TI  - Traumatic hyphaema in a patient with severe haemophilia B.

PMID- 24870610
TI  - Impairment of nitric oxide synthase but not heme oxygenase accounts for
      baroreflex dysfunction caused by chronic nicotine in female rats.
AB  - We recently reported that chronic nicotine impairs reflex chronotropic activity
      in female rats. Here, we sought evidence to implicate nitric oxide synthase (NOS)
      and/or heme oxygenase (HO) in the nicotine-baroreflex interaction. Baroreflex
      curves relating changes in heart rate to increases (phenylephrine) or decreases
      (sodium nitroprusside) in blood pressure were generated in conscious female rats
      treated with nicotine or saline in absence and presence of pharmacological
      modulators of NOS or HO activity. Compared with saline-treated rats, nicotine (2
      mg/kg/day i.p., for 14 days) significantly reduced the slopes of baroreflex
      curves, a measure of baroreflex sensitivity (BRS). Findings that favor the
      involvement of NOS inhibition in the nicotine effect were (i) NOS inhibition
      (Nomega-Nitro-L-arginine methyl ester, L-NAME) reduced BRS in control rats but
      failed to do so in nicotine-treated rats, (ii) L-arginine, NO donor, reversed the
      BRS inhibitory effect of nicotine. Alternatively, HO inhibition (zinc
      protoporphyrin IX, ZnPP) had no effect on BRS in nicotine- or control rats and
      failed to reverse the beneficial effect of L-arginine on nicotine-BRS
      interaction. Similar to female rats, BRS was reduced by L-NAME, but not ZnPP, in
      male rats and the L-NAME effect was not accentuated after concomitant
      administration of nicotine. Baroreflex dysfunction caused by nicotine in female
      rats was blunted after supplementation with hemin (HO inducer) but not
      tricarbonyldichlororuthenium(II) dimer (CORM-2), a carbon monoxide (CO) releasing
      molecule, or bilirubin, the breakdown product of heme catabolism. The
      facilitatory effect of hemin was abolished upon simultaneous treatment with L
      NAME or 1H-[1], [2], [4] oxadiazolo[4,3-a] quinoxalin-1-one (inhibitor of soluble
      guanylate cyclase, sGC). The activities of HO and NOS in brainstem tissues were
      also significantly increased by hemin. Thus, the inhibition of NOS, but not HO,
      accounts for the baroreflex depressant of chronic nicotine. Further, hemin
      alleviates the nicotine effect through a mechanism that is NOS/sGC but not CO or
      bilirubin-dependent. 

PMID- 24870614
TI  - Allele compensation in tip60+/- mice rescues white adipose tissue function in
      vivo.
AB  - Adipose tissue is a key regulator of energy homestasis. The amount of adipose
      tissue is largely determined by adipocyte differentiation (adipogenesis), a
      process that is regulated by the concerted actions of multiple transcription
      factors and cofactors. Based on in vitro studies in murine 3T3-L1 preadipocytes
      and human primary preadipocytes, the transcriptional cofactor and
      acetyltransferase Tip60 was recently identified as an essential adipogenic
      factor. We therefore investigated the role of Tip60 on adipocyte differentiation
      and function, and possible consequences on energy homeostasis, in vivo. Because
      homozygous inactivation results in early embryonic lethality, Tip60+/- mice were
      used. Heterozygous inactivation of Tip60 had no effect on body weight, despite
      slightly higher food intake by Tip60+/- mice. No major effects of heterozygous
      inactivation of Tip60 were observed on adipose tissue and liver, and Tip60+/-
      displayed normal glucose tolerance, both on a low fat and a high fat diet. While
      Tip60 mRNA was reduced to 50% in adipose tissue, the protein levels were
      unaltered, suggesting compensation by the intact allele. These findings indicate
      that the in vivo role of Tip60 in adipocyte differentiation and function cannot
      be properly addressed in Tip60+/- mice, but requires the generation of adipose
      tissue-specific knock out animals or specific knock-in mice. 

PMID- 24870616
TI  - Recombinant deamidated mutants of Erwinia chrysanthemi L-asparaginase have
      similar or increased activity compared to wild-type enzyme.
AB  - The enzyme Erwinia chrysanthemi L-asparaginase (ErA) is an important
      biopharmaceutical product used in the treatment of acute lymphoblastic leukaemia.
      Like all proteins, certain asparagine (Asn) residues of ErA are susceptible to
      deamidation to aspartic acid (Asp), which may be a concern with respect to enzyme
      activity and potentially to pharmaceutical efficacy. Recombinant ErA mutants
      containing Asn to Asp changes were expressed, purified and characterised. Two
      mutants with single deamidation sites (N41D and N281D) were found to have
      approximately the same specific activity (1,062 and 924 U/mg, respectively) as
      the wild-type (908 U/mg). However, a double mutant (N41D N281D) had an increased
      specific activity (1261 U/mg). The N41D mutation conferred a slight increase in
      the catalytic constant (k cat 657 s(-1)) when compared to the WT (k cat 565 s(
      1)), which was further increased in the double mutant, with a k cat of 798 s(-1).
      Structural analyses showed that the slight changes caused by point mutation of
      Asn41 to Asp may have reduced the number of hydrogen bonds in this alpha-helical
      part of the protein structure, resulting in subtle changes in enzyme turnover,
      both structurally and catalytically. The increased alpha-helical content observed
      with the N41D mutation by circular dichroism spectroscopy correlates with the
      difference in k cat, but not K m. The N281D mutation resulted in a lower
      glutaminase activity compared with WT and the N41D mutant, however the N281D
      mutation also imparted less stability to the enzyme at elevated temperatures.
      Taken as a whole, these data suggest that ErA deamidation at the Asn41 and Asn281
      sites does not affect enzyme activity and should not be a concern during
      processing, storage or clinical use. The production of recombinant deamidated
      variants has proven an effective and powerful means of studying the effect of
      these changes and may be a useful strategy for other biopharmaceutical products. 

PMID- 24870617
TI  - Optimization of the immunogenicity of a DNA vaccine encoding a bacterial outer
      membrane lipoprotein.
AB  - Bacterial outer membrane lipoproteins represent potent immunogens for the design
      of recombinant subunit vaccines. However, recombinant lipoprotein production and
      purification could be a challenge notably in terms of expression yield, protein
      solubility, and post-translational acylation. Together with the cost
      effectiveness, facilitated production, and purification as well as good
      stability, DNA-based vaccines encoding lipoproteins could become an alternative
      strategy for antibacterial vaccinations. Although the immunogenicity and the
      efficacy of DNA-based vaccines can be demonstrated in small rodents, such vaccine
      candidates could request concrete optimization as they are weak immunogens in
      primates and humans and particularly when administered by conventional injection.
      Therefore, the goal of the present study was to optimize the immunogenicity of a
      DNA vaccine encoding an outer membrane lipoprotein. LipL32, the major outer
      membrane protein from pathogenic Leptospira, was selected as a model antigen. We
      evaluated the influence of antigen secretion, the in vivo DNA delivery by
      electroporation, the adjuvant co-administration, as well as the heterologous
      prime-boost regimen on the induction of anti-LipL32 specific immune responses.
      Our results clearly showed that, following transfections, a DNA construct based
      on the authentic full-length LipL32 gene (containing leader sequence and the N
      terminus cysteine residue involved in the protein anchoring) drives antigen
      secretion with the same efficiency as a plasmid-encoding anchor-less LipL32 and
      for which the bacterial leader sequence was replaced with a viral signal peptide.
      The in vivo DNA delivery by electroporation drastically enhanced the production
      of strong Th1 responses characterized by specific IgG2a antibodies and the
      IFNgamma secretion in a restimulation assay, regardless of the DNA constructs
      used. In comparison with the heterologous prime-boost regimen, the homologous
      prime-boost vaccinations with DNA co-administrated with polyinosinic
      polycytidylic acid (poly I:C) generated the highest specific IgG and IgG2a titers
      as well as the greatest IFNgamma production. Taken together, these data suggest
      that optimization of outer membrane lipoprotein secretion is not critical for the
      induction of antigen-specific responses through DNA vaccination. Moreover, the
      potent antibody response induced by DNA plasmid encoding lipoprotein formulated
      with poly I:C and delivered through electroporation provides the rationale for
      the design of new prophylactic vaccines against pathogenic bacteria. 

PMID- 24870618
TI  - Applications of TALENs and CRISPR/Cas9 in human cells and their potentials for
      gene therapy.
AB  - The newly developed TALENs and emerging CRISPR/Cas9 have spurred interests in the
      field of genome engineering because of their ease of customization and high
      efficient site-specific cleavages. Although these novel technologies have been
      successfully used in many types of cells, it is of great importance to apply them
      in human-derived cells to further observe and evaluate their clinical potentials
      in gene therapy. Here, we review the working mechanism of TALEN and CRISPR/Cas9,
      their effectiveness and specificity in human cells, and current methods to
      enhance efficiency and reduce off-target effects. Besides, CCR5 gene was chosen
      as a target example to illustrate their clinical potentials. Finally, some
      questions are raised for future research and for researchers to consider when
      making a proper choice bases on different purposes.

PMID- 24870619
TI  - SLX2 interacting with BLOS2 is differentially expressed during mouse oocyte
      meiotic maturation.
AB  - Gametogenesis is a complex biological process of producing cells for sexual
      reproduction. Xlr super family members containing a conserved COR1 domain play
      essential roles in gametogenesis. In the present study, we identified that Slx2,
      a novel member of Xlr super family, is specifically expressed in the meiotic
      oocytes, which is demonstrated by western blotting and immunohistochemistry
      studies. In the first meiotic prophase, SLX2 is unevenly distributed in the
      nuclei of oocytes, during which phase SLX2 is partly co-localized with SYCP3 in
      synaptonemal complex and gammaH2AX in the nucleus of oocytes. Interestingly, the
      localization of SLX2 was found to be switched into the cytoplasm of oocytes after
      prometaphase I during oocyte maturation. Furthermore, yeast two-hybrid and
      coimmunoprecipitation studies demonstrated that SLX2 interacts with BLOS2, which
      is a novel centrosome-associated protein, and co-localized with gamma-Tubulin,
      which is a protein marker of chromosome segregation in meiosis. These results
      indicated that SLX2 might get involved in chromosomes segregation during meiosis
      by interaction with BLOS2. In conclusion, SLX2 might be a novel gametogenesis
      related protein that could play multiple roles in regulation of meiotic processes
      including synaptonemal complex assembly and chromosome segregation. 

PMID- 24870621
TI  - Fluorescence virus-guided capturing system of human colorectal circulating tumour
      cells for non-invasive companion diagnostics.
AB  - BACKGROUND: Molecular-based companion diagnostic tests are being used with
      increasing frequency to predict their clinical response to various drugs,
      particularly for molecularly targeted drugs. However, invasive procedures are
      typically required to obtain tissues for this analysis. Circulating tumour cells
      (CTCs) are novel biomarkers that can be used for the prediction of disease
      progression and are also important surrogate sources of cancer cells. Because
      current CTC detection strategies mainly depend on epithelial cell-surface
      markers, the presence of heterogeneous populations of CTCs with epithelial and/or
      mesenchymal characteristics may pose obstacles to the detection of CTCs. METHODS:
      We developed a new approach to capture live CTCs among millions of peripheral
      blood leukocytes using a green fluorescent protein (GFP)-expressing attenuated
      adenovirus, in which the telomerase promoter regulates viral replication (OBP
      401, TelomeScan). RESULTS: Our biological capturing system can image epithelial
      and mesenchymal tumour cells with telomerase activities as GFP-positive cells.
      After sorting, direct sequencing or mutation-specific PCR can precisely detect
      different mutations in KRAS, BRAF and KIT genes in epithelial, mesenchymal or
      epithelial-mesenchymal transition-induced CTCs, and in clinical blood samples
      from patients with colorectal cancer. CONCLUSIONS: This fluorescence virus-guided
      viable CTC capturing method provides a non-invasive alternative to tissue biopsy
      or surgical resection of primary tumours for companion diagnostics.

PMID- 24870620
TI  - MicroRNA-29c mediates initiation of gastric carcinogenesis by directly targeting
      ITGB1.
AB  - OBJECTIVE: Gastric cancer (GC) remains difficult to cure due to heterogeneity in
      a clinical challenge and the molecular mechanisms underlying this disease are
      complex and not completely understood. Accumulating evidence suggests that
      microRNAs (miRNAs) play an important role in GC, but the role of specific miRNAs
      involved in this disease remains elusive. We performed next generation sequencing
      (NGS)-based whole-transcriptome profiling to discover GC-specific miRNAs,
      followed by functional validation of results. DESIGN: NGS-based miRNA profiles
      were generated in matched pairs of GCs and adjacent normal mucosa (NM).
      Quantitative RT-PCR validation of miR-29c expression was performed in 274 gastric
      tissues, which included two cohorts of matched GC and NM specimens. Functional
      validation of miR-29c and its gene targets was undertaken in cell lines, as well
      as K19-C2mE and K19-Wnt1/C2mE transgenic mice. RESULTS: NGS analysis revealed
      four GC-specific miRNAs. Among these, miR-29c expression was significantly
      decreased in GC versus NM tissues (p<0.001). Ectopic expression of miR-29c mimics
      in GC cell lines resulted in reduced proliferation, adhesion, invasion and
      migration. High miR-29c expression suppressed xenograft tumour growth in nude
      mice. Direct interaction between miR-29c and its newly discovered target, ITGB1,
      was identified in cell lines and transgenic mice. MiR-29c expression demonstrated
      a stepwise decrease in wild type hyperplasia-dysplasia cascade in transgenic mice
      models of GC. CONCLUSIONS: MiR-29c acts as a tumour suppressor in GC by directly
      targeting ITGB1. Loss of miR-29c expression is an early event in the initiation
      of gastric carcinogenesis and may serve as a diagnostic and therapeutic biomarker
      for patients with GC.

PMID- 24870622
TI  - Preliminary report: modulation of parasympathetic nervous system tone influences
      oesophageal pain hypersensitivity.
AB  - OBJECTIVES: Autonomic nervous system dysfunction has been implicated in visceral
      hypersensitivity. However, the specific contribution of the parasympathetic
      nervous system (PNS) is unclear. We aimed to determine whether physiological and
      pharmacological manipulation of parasympathetic tone influences the development
      of hypersensitivity in a validated model of acid-induced oesophageal pain.
      DESIGN: Prior to, and following, a 30-min distal oesophageal infusion of 0.15 M
      hydrochloric acid, pain thresholds to electrical stimulation were determined in
      the proximal non-acid exposed oesophagus in healthy subjects. Validated
      sympathetic (skin conductance response) and parasympathetic (cardiac vagal tone)
      parameters were measured at baseline and continuously thereafter. In study 1, 55
      subjects were randomised in a pragmatic blinded crossover design to receive deep
      breathing or un-paced breathing during acid infusion. In study 2, 32 subjects
      were randomised in a blinded, crossover design to receive intravenous atropine or
      placebo (saline) with deep breathing during acid infusion. RESULTS: Study 1: Deep
      breathing increased cardiac vagal tone (2.1+/-2.3 vs -0.3+/-2.3, p=0.0006) with
      concomitant withdrawal of skin conductance response (-0.6+/-4.9 vs 3+/-4.8,
      p=0.03) in comparison with un-paced breathing. Deep breathing prevented the
      development of acid-induced oesophageal hypersensitivity in comparison with sham
      breathing (p=0.0001). Study 2: Atropine, in comparison with placebo, blocked the
      attenuating effect of deep breathing on the development of acid-induced
      oesophageal hypersensitivity (p=0.046). CONCLUSIONS: The development of
      oesophageal hyperalgesia is prevented by physiologically increasing
      parasympathetic tone. This effect is pharmacologically blocked with atropine,
      providing evidence that the PNS influences the development of oesophageal pain
      hypersensitivity.

PMID- 24870623
TI  - Fever and right upper quadrant pain in a 24-year-old male. Caroli disease and
      splenomegaly suggesting portal hypertension.

PMID- 24870624
TI  - Screening for bile acid diarrhoea in suspected irritable bowel syndrome.

PMID- 24870625
TI  - Pd/NHC-catalyzed enantiospecific and regioselective Suzuki-Miyaura arylation of 2
      arylaziridines: synthesis of enantioenriched 2-arylphenethylamine derivatives.
AB  - A palladium-catalyzed stereospecific and regioselective cross-coupling of
      enantiopure 2-arylaziridines with arylboronic acids under mild conditions to
      construct a tertiary stereogenic center has been developed. N-heterocyclic
      carbene (NHC) ligands efficiently promote the coupling, suppressing beta-hydride
      elimination. The enantiospecific cross-coupling allowed us for preparation of a
      series of biologically important 2-arylphenethylamine derivatives in an
      enantiopure form. 

PMID- 24870626
TI  - Callogobius liolepis Bleeker, a senior synonym of Gobiopsis aporia Lachner and
      McKinney (Teleostei: Gobiidae: Gobiopsis).
AB  - Callogobius liolepis Bleeker in Koumans was briefly described from two specimens
      from Ambon. A later, more detailed description by Koumans was apparently based on
      Bleeker's unpublished description and specimens of C. okinawae (Snyder),
      considerably complicating the taxonomy of several species. Re-examination of the
      syntypes identifies C. liolepis as a species of the genus Gobiopsis Steindachner
      due to the absence of raised vertical ridges of papillae that characterise
      Callogobius and the presence of barbels in a pattern unique among gobiids to a
      subset of Gobiopsis. Gobiopsis liolepis (Bleeker) is determined as the senior
      synonym of G. aporia Lachner and McKinney based on the absence of head pores
      combined with the presence of a series of tightly spaced papillae over the eye,
      lateral scale counts of 36-42, pectoral-fin ray counts of 20-21, dorsal-fin ray
      counts VI+I,10 and anal-fin ray counts of I,9. The larger syntype is designated
      the lectotype and the smaller the paralectotype. Specimens identified as C.
      liolepis in museums or the literature are likely referable to C. okinawae
      (Snyder) or C. bifasciatus (Smith). 

PMID- 24870627
TI  - New genera of Afrotropical limosinine sphaerocerids (Diptera: Sphaeroceridae).
AB  - Eight new genera of the subfamily Limosininae are described from the Afrotropical
      region: Afrolimosina gen. n. (type species A. albitarsis sp. n.), Biphallapodema
      gen. n. (type species B. polydentata sp. n., additional species B. oligodentata
      sp. n.), Chelilimosina gen. n. (type species Ch. baloghi sp. n.), Mislocatus gen.
      n. (type species Ceroptera ealensis Vanschuytbroeck, 1951), Oligochaetosella gen.
      n. (type species O. inconspicua sp. n.), Permixtolimosina gen. n. (type species
      P. sexsetosa sp. n.), Preepiphallus gen. n. (type species P. nitidifacies sp. n.,
      additional species P. endrodyi sp. n.), Subacuminiseta gen. n. (type species S.
      minor sp. n.). Comparisons to the key for the identification of Old World genera
      of Limosininae (Papp 2008) are given. With 118 original figures. 

PMID- 24870629
TI  - Notes on the first instar larvae of Ctenophora and Nephrotoma (Diptera,
      Tipulidae).
AB  - 1830 egg-larvae of 7 species belonging to long palped crane flies (Tipulidae):
      Ctenophora guttata Meigen, Nephrotoma pratensis Linnaeus, N. dorsalis Fabricius,
      N. scurra Meigen, N. flavescens Linnaeus, N. submaculosa Edwards and N. crocata
      Linnaeus were obtained from 22 females captured in Lithuania in 2011-2012. It
      took from five days to more than three weeks for eggs to hatch. Crane flies have
      four instars of larvae. Second, third and the last instar larvae are very
      similar, when the first instar or egg-larvae differs radically. Descriptions and
      illustrations of external morphology, chaetotaxy of abdominal segments,
      characters of head capsules and last abdominal segments are given for the
      previously unknown first instar larvae of Ct. guttata, N. crocata, N. dorsalis,
      N. flavescens, N. pratensis, N. scurra and poorly known N. submaculosa. It was
      found out that difference of head capsule and last abdominal segment among the
      first instar larvae of above mentioned species of genus Nephrotoma are more
      obvious than in last instar. During this study it was found, that such characters
      as shape of apical teeth of mandible, shape of basal segment of antenna and
      number of sensillae, shape of hypostomium and arrangement of sensory structures
      on labrum, differ among egg-larvae of Nephrotoma. It was found, that pads on
      frontal part of prothorax and shape of lateral plates of egg-larvae labrum of
      Nephrotoma differ significantly from that of Ctenophora and could be used as
      genus separating characters.  

PMID- 24870628
TI  - Three new species of Seira Lubbock (Collembola, Entomobryidae) from Caatinga
      Domain, northeastern Brazil.
AB  - Three new species of Seira Lubbock, Seira jiboiensis sp.nov., Seira primaria sp.
      nov. and Seira harena sp.nov. from Neotropical Region are described and
      illustrated. All species were collected from humid areas of Caatinga
      Biogeographic Domain, northeastern Brazil. Seira jiboiensis sp.nov. shows some
      similarities with S. mendoncea Bellini & Zeppelini and S. ritae Bellini &
      Zeppelini, while S. primaria sp.nov. resembles S. pseudoannulata Bellini &
      Zeppelini and S. paraibensis Bellini & Zeppelini in dorsal chaetotaxy in some
      aspects. Seira harena sp.nov. belongs to a subgroup of Seira originally described
      in the subgenus Lepidocyrtinus Borner, which has modified macrochaetae on distal
      manubrium and proximal dens, like S. prodiga (Arle), S. xinguensis (Arle) and S.
      nigrans (Arle). 

PMID- 24870630
TI  - New species of Latreillopsis Henderson, 1888 (Brachyura: Homolidae) and
      Neopalicus Moosa & Serene, 1981 (Brachyura: Palicidae) from the Hawaiian Islands.
AB  - Two new species of brachyuran crabs belonging to Latreillopsis Henderson, 1888
      (Homolidae) and Neopalicus Moosa & Serene, 1981 (Palicidae) respectively are
      described from Maui, Hawai'i. The new species of Latreillopsis is distinguished
      from its nine congeners by a granular carapace and pereopods, a triangular G1,
      and by the distinctive ornamentation of its carapace and third maxillipeds; the
      new species of Neopalicus from its three congeners by the presence of three
      triangular anterolateral teeth, absence of extensions on the outer margins of the
      P3 and P4 propodi, dentate inner margins of the P3, P4 dactyli, and absence of
      ridges on the female abdomen. Also listed is Latreillia metanesa Williams, 1982
      (Latreilliidae), recorded for the first time from the archipelago since its
      description from Albatross material collected in 1902. 

PMID- 24870631
TI  - Morphological and genetic differentiation of heteromorphy in Labidocera rotunda
      (Copepoda, Calanoida, Pontellidae).
AB  - The pontellid calanoid Labidocera rotunda Mori, 1929 is relatively widespread in
      the inshore surface waters of East Asia. In this study, some heteromorphic
      specimens have been observed with extreme morphological discrepancies in the
      female, including the genital double-somite, the second urosomite, the caudal
      rami, and the fifth leg. To evaluate the validity of species assignment of the
      morphological variants, we analyzed the DNA sequences of two mitochondrial genes,
      16S rRNA and cytochrome oxidase subunit I (mtCOI). The specimens were collected
      in the Yellow Sea, the East China Sea and the East Sea (Sea of Japan) around
      Korea. They differed by <2.9% for mt16S rRNA and by 3.7%-4.7% for mtCOI,
      suggesting that they are conspecific despite their considerable morphological
      differences. In contrast, Labidocera japonica Mori, 1935, a morphologically
      similar species to L. rotunda, displayed interspecific variation of 6.1%-7.2% for
      mt16S rRNA and 15.1%-16.7% for mtCOI. 

PMID- 24870632
TI  - A new species of the Yelicones Cameron (Hymenoptera: Braconidae: Rogadinae) from
      Thailand.
AB  - Yelicones samaesanensis Butcher, new species, is described and illustrated based
      on a female and male specimens collected at light trap in Chonburi province,
      Thailand. This wasp is the tenth species of Yelicones described from the East
      Palaearctic and Oriental regions. Y. samaesanensis appears closest to Y.
      contractus Papp from Vietnam and India. A key is included to differentiate Y.
      samaesanensis from the similar species. 

PMID- 24870633
TI  - A new genus of Phaneropterinae (Orthoptera: Ensifera: Tettigoniidae) from Central
      Africa.
AB  - The new genus Pseudoplangia is described for Plangia laminifera Karsch, 1896. Its
      general aspect is similar to that of the genus Plangia Stal, 1873, but it differs
      remarkably in the vertex width, in the shape of eyes, that are oval and elongate,
      in the length of mid femora, that are shorter than pronotum length, in the shape
      of fore and mid legs that are very much laterally compressed, and in the presence
      of broad-based spines on the hind tibiae. 

PMID- 24870634
TI  - A review of the genus Rhipidia Meigen from China, with descriptions of seven new
      species (Diptera, Limoniidae).
AB  - The genus Rhipidia Meigen, 1818 from China is reviewed. Twenty-one species are
      presented, of which seven species, Rhipidia (Rhipidia) bilobata sp. nov., R. (R.)
      flava sp. nov., R. (R.) lobifera sp. nov., R. (R.) longa sp. nov., R. (R.) sejuga
      sp. nov., R. (R.) shennongjiensis sp. nov., and R. (R.) spinosa sp. nov., are
      described as new to science, and one species, R. (R.) reductispina Savchenko,
      1983, is recorded from China for the first time. A key to the species of the
      genus Rhipidia from China is given. 

PMID- 24870635
TI  - A new aetosaur from the Upper Triassic of the Santa Maria Formation, southern
      Brazil.
AB  - Aetosaurs are armored pseudosuchian archosaurs widespread in Upper Triassic
      units. In South America, four taxa were previously recorded: Aetosauroides
      scagliai, Neoaetosauroides engaeus, Aetobarbakinoides brasiliensis, and
      Chilenosuchus forttae. Herein we describe a new Late Triassic juvenile aetosaur
      from the Santa Maria Formation of southern Brazil, Polesinesuchus aurelioi gen.
      et sp. nov., increasing the paleobiodiversity of this interesting group to five
      taxa in Western Gondwana. The holotype is composed of cranial (parietal and
      braincase) and postcranial elements (cervical, dorsal, sacral, caudal vertebrae,
      both scapulae, a humerus, ilium, pubis, ischium, tibia, a partial right pes, and
      anterior and mid-dorsal paramedian osteoderms). It belongs to a juvenile
      individual, as its neurocentral sutures are open in all vertebrae, and also due
      to its small size. However, future paleohistological investigation is necessary
      to fully corroborate this assumption. This new taxon is distinguished from all
      other aetosaurs by the presence of an unique combination of character states (not
      controlled by ontogeny) such as: cervical vertebrae with prezygapophyses widely
      extending laterally through most of the anterior edge of the diapophyses; absence
      of hyposphene articulations in both cervical and mid-dorsal vertebrae; presence
      of a ventral keel in cervical vertebrae; anterior and mid-dorsal vertebrae
      without a lateral fossa in their centra; expanded proximal end of scapula;
      anteroposteriorly expanded medial portion of scapular blade; a short humerus with
      a robust shaft; and a dorsoventral and very low iliac blade with a long anterior
      process which slightly exceeds the pubic peduncle. Regarding its phylogenetic
      relationships, the present analysis placed Polesinesuchus as the sister taxon of
      Aetobarbakinoides and both as sister taxa of the unnamed monophyletic clade
      Desmatosuchinae plus Typothoracisinae.  

PMID- 24870636
TI  - Deep-Sea decapod crustaceans (Caridea, Polychelida, Anomura and Brachyura)
      collected from the Nikko Seamounts, Mariana Arc, using a remotely operated
      vehicle "Hyper-Dolphin".
AB  - Samples and images of deep-water benthic decapod crustaceans were collected from
      the Nikko Seamounts, Mariana Arc, at depths of 520-680 m, by using the remotely
      operate vehicle "Hyper-Dolphin", equipped with a high definition camera, digital
      camera, manipulators and slurp gun (suction sampler). The following seven species
      were collected, of which three are new to science: Plesionika unicolor n. sp.
      (Caridea: Pandalidae), Homeryon armarium Galil, 2000 (Polychelida: Polychelidae),
      Eumunida nikko n. sp. (Anomura: Eumunididae), Michelopagurus limatulus
      (Henderson, 1888) (Anomura: Paguridae), Galilia petricola n. sp. (Brachyura:
      Leucosiidae), Cyrtomaia micronesica Richer de Forges & Ng, 2007 (Brachyura:
      Inachidae), and Progeryon mus Ng & Guinot, 1999 (Brachyura: Progeryonidae).
      Affinities of these three new species are discussed. All but H. armarium are
      recorded from the Japanese Exclusive Economic Zone for the first time. Brief
      notes on ecology and/or behavior are given for each species.

PMID- 24870637
TI  - Redefinition of Cosmolaelaps Berlese (Acari: Laelapidae) and description of five
      new species from Brazil.
AB  - Cosmolaelaps Berlese, 1903 was originally described as a subgenus of Laelaps
      Koch. More recently, this group has been treated at the generic level or as a
      subgenus of Hypoaspis Canestrini, 1885. One of the objectives of the present
      paper is to provide a detailed characterisation of Cosmolaelaps, here considered
      at the generic level, a group that was poorly characterised in its original
      description as well as in subsequent publications. It is most closely related to
      Stratiolaelaps Berlese, from which it can usually be distinguished by the
      presence of extra paired and unpaired setae on the opisthonotal region of the
      dorsal shield, as well as by not having hypertrophied chelicerae or corniculi. A
      total of 108 species belong to Cosmolaelaps, including the new species described
      here. Five other species may also belong to this genus, but the available
      published information does not allow their conclusive placement. The Brazilian
      fauna of Hypoaspidinae is poorly known, but Cosmolaelaps seems to be well
      represented in Brazil. Thus, the second objective of this paper is to describe
      five new species of Cosmolaelaps from that country, namely C. barbatus sp. nov.,
      C. busolii sp. nov., C. confinisetarum sp. nov., C. jaboticabalensis sp. nov. and
      C. oliveirai sp. nov.

PMID- 24870638
TI  - A third new Cyrtodactylus (Squamata: Gekkonidae) from Ba Den Mountain, Tay Ninh
      Province, southern Vietnam.
AB  - We describe the third new species of the genus Cyrtodactylus from Ba Den
      Mountain, Tay Ninh Province, southern Vietnam based on a type series consisting
      of eleven specimens. Cyrtodactylus thuongae sp. nov. is distinguished from the
      remaining Indochinese Bent-toed Geckos by a combination of the following
      morphological characters: size medium, with a maximum SVL of 77.6 mm; dorsal
      pattern consisting of blotches between limbs and on occiput and a sometimes
      medially opened nuchal loop; dorsal tubercles in 16-18 irregular rows; ventrals
      in 29-44 longitudinal rows at midbody; lateral skin folds present, lacking
      tubercles; femoral pore series separated from precloacal pore series in males, 0
      3 on each side; precloacal pores in males absent or only one; enlarged femoral
      scales and precloacal scales present, separated by a series of 15-16 smaller
      scales; postcloacal spurs two or three; subcaudal scales slightly enlarged. This
      is the 32<sup>nd</sup> described Cyrtodactylus species from Vietnam. 

PMID- 24870639
TI  - A new species of Cardiodactylus (Orthoptera: Grylloidea: Eneopterinae) from
      Singapore.
AB  - Cardiodactylus is a speciose cricket genus belonging to the subfamily
      Eneopterinae. One new species of Cardiodactylus from Singapore is described:
      Cardiodactylus admirabilis Tan & Robillard n. sp. Acoustic analysis is also
      performed on the male calling song. A key to species of Eneopterinae from
      Singapore is provided. 

PMID- 24870640
TI  - A new troglobitic species of the spider genus Tengella Dahl (Araneae,
      Tengellidae) from Chiapas, Mexico.
AB  - A new species of troglobitic spider of the genus Tengella Dahl is described from
      Mexico: Tengella kalebi new species, from a limestone cave in Chiapas, Mexico.
      The species is described on the basis of adult male and females. This is the
      fifth species described for the genus Tengella, the third species described from
      Mexico, the first species that has notable troglomorphic modifications, and the
      first ecribellate Tengella species. 

PMID- 24870641
TI  - Further records of pseudoscorpions (Arachnida, Pseudoscorpiones) from Saudi
      Arabia.
AB  - Five species of pseudoscorpions are recorded from the southwestern mountains of
      the Kingdom of Saudi Arabia. Pseudochthonius arabicus Mahnert n. sp. is described
      as new to science; this genus was previously known only from sub-Saharan Africa
      and tropical South America and represents the first record of the family
      Chthoniidae from the Arabian Peninsula. Paratemnoides ellingseni (Beier, 1932), a
      widespread species in tropical Africa, and Withius piger (Simon, 1878) are added
      to the faunal list of Saudi Arabia. Minniza monticola Mahnert, 1991 and
      Rhacochelifer sonyae Mahnert, 1991 are apparently endemic to the southwestern
      mountains of Saudi Arabia. 

PMID- 24870642
TI  - On the identities of the molluscan names described in A Short Zoology of Tahiti
      in the Society Islands by Anthony Curtiss in 1938 (Mollusca: Cephalopoda,
      Gastropoda).
AB  - Anthony Curtiss described two species of cephalopod and nine species of gastropod
      molluscs from Tahiti. Herein, we discuss and determine the identities of these
      eleven names. Ten of these names are considered to be junior subjective synonyms
      of well-known taxa, and one an unavailable name. 

PMID- 24870643
TI  - New species and records of scale mites (Acari: Pterygosomatidae) from Arabian
      Agamid lizards (Squamata: Agamidae).
AB  - Two new species of pterygosomatid mites parasitizing lizards of the family
      Agamidae are described: Pterygosoma aqabensis sp. nov. from Pseudotrapelus
      aqabensis Melnikov et al. and Pterygosoma dhofarensis sp.nov. from Pseudotrapelus
      dhofarensis Melnikov and Pierson both from Arabian Peninsula. Pterygosoma
      aqabensis sp. nov. is most closely related to P. dhofarensis sp. nov. but differs
      by the presence of subcapitular setae n, setae vFI and vGIV, 14-21 pairs of the
      antero-dorsal setae, 4 pairs of dorso-median setae dm, 5-6 pairs of the postero
      lateral setae and 7 pairs of pseudoanal setae ps, palp setae dG and dF are
      subequal in the length and setae vm3 are slightly serrated. P. dhofarensis sp.
      nov. is similar to P. sinaita Jack, 1961 but in the new species setae dm1 are
      serrated and setae dm2 are filiform, 3 or 4 pairs of the medio-lateral setae and
      2 pairs of peripheral setae are present, setae dGI are absent. A redescription of
      Pterygosoma adramitana Jack, 1961 from the type host Acanthocercus adramitanus
      (Anderson) (Agamidae) is given.

PMID- 24870644
TI  - A new species of sponge-dwelling Oukuriella (Chironomidae) from Brazil.
AB  - Oukuriella Epler, 1986 is an exclusively Neotropical genus that comprises two
      well supported clades: inhabitants of freshwater sponges and inhabitants of
      immersed wood (saproxylophilic). In this work, males of a new chironomid species,
      Oukuriella froehlichi sp. n., are described and illustrated. Specimens were
      collected near stream in the Brazilian Atlantic Forest. Phylogenetic analyses
      performed in this study show that the newly discovered species belongs in the
      clade of freshwater sponge inhabitants.

PMID- 24870645
TI  - A new species of upland Stream Toad of the genus Ansonia Stoliczka, 1870 (Anura:
      Bufonidae) from northeastern Peninsular Malaysia.
AB  - A new species of Ansonia is described based on genetic and morphological
      differentiation. Ansonia lumut sp. nov. is most closely related to three other
      Peninsular Malaysian species, A. penangensis, A. malayana, and A. jeetsukumarani
      but differs from these and other congeners by at least 6.9% sequence divergence
      at the 12S, 16S rRNA and t-RNA-val genes and the following combination of
      morphological characters: (1) SVL 21.0-23.6 mm in males, 27.7-31.6 mm in females;
      (2) first finger shorter than second; (3) interorbital and tarsal ridges absent;
      (4) light interscapular spot absent; (5) presence of large, yellow rictal
      tubercle; (6) dorsum black with greenish-yellow reticulations; (7) flanks with
      small yellow spots; (8) fore and hind limbs with yellow cross-bars; and (9)
      venter light gray with fine, white spotting. 

PMID- 24870646
TI  - Neophyllobius lorestanicus sp. nov. and N. ostovani sp.nov. (Acari: Camerobiidae)
      from Iran.
AB  - Two new species of the genus Neophyllobius Berlese, 1886 are described:
      Neophyllobius lorestanicus sp. nov. collected from soil under Prunus domestica L.
      (Rosaceae) in Markazi province and Neophyllobius ostovani sp. nov. from soil and
      rotten leaves of oak trees in Fars province, Iran. A key to all known Iranian and
      Turkish species of Neophyllobius is provided. 

PMID- 24870647
TI  - Two new potamid crabs, Yuexipotamon arcophallus new genus, new species and
      Minutomon shanweiense new genus, new species, (Crustacea: Decapoda: Brachyura:
      Potamidae) from southern China.
AB  - Two new Chinese genera and species of freshwater crabs, Yuexipotamon arcophallus,
      new genus, new species, and Minutomon shanweiense, new genus, new species, are
      described from Zhaoqing City and Shanwei City, respectively. The former is
      superficially closest to Huananpotamon Dai & Ng, 1994, while the latter resembles
      Sinopotamon Bott, 1967, and Mediapotamon Dai, 1995. The two new genera, however,
      possess distinctive combinations of carapace, third maxilliped, male thoracic
      sternal and first gonopodal characters that easily distinguish them from other
      genera. Notes on the general biology of the two new species are also given. 

PMID- 24870648
TI  - Shortcrowna, a new genus of Evacanthinae (Hemiptera: Cicadellidae) from China.
AB  - The paper deals with a new leafhopper genus of Evacanthinae, Shortcrowna gen.
      nov., and four species of the genus, including three new combinations and one new
      species, Shortcrowna biguttata (Li & Wang, 2002) comb. nov., Shortcrowna
      flavocapitata (Kato, 1933) comb. nov., Shortcrowna nigrimargina (Li & Wang, 2002)
      comb. nov., Shortcrowna leishanensis sp. nov.. The differences between the new
      genus and the closely related genus Bundera Distant are discussed. A key to
      distinguish all species of the genus is given, and illustrations of genitalia are
      provided. The type specimens of new species are deposited in the Institute of
      Entomology, Guizhou University (GUGC). 

PMID- 24870649
TI  - A new species of Hetereleotris (Perciformes: Gobiidae) from the Red Sea.
AB  - A new species of the genus Hetereleotris is described from the Gulf of Aqaba, Red
      Sea, on the basis of two specimens. Hetereleotris psammophila sp. nov. is unique
      among the species of the genus Hetereleotris, except for H. diademata, in lacking
      scales and head pores. The new species differs from the morphologically similar
      H. diademata in having fewer rays in the second dorsal and anal fins, and in
      coloration. The habitat preference of the new species for open sand area close to
      coral reefs in 8-21 m and its nocturnal habits are unusual for species of the
      genus Hetereleotris. 

PMID- 24870650
TI  - Description of the final-instar larva of Heliogomphus selysi Fraser (Odonata:
      Gomphidae).
AB  - The final instar larva of Heliogomphus selysi Fraser, 1925, is described and
      illustrated for the first time based on specimens collected in Ratchaburi
      province, Thailand. Antennae, legs and paraprocts are similar morphologically to
      H. kelantanensis and H. scorpio but with a unique combination of dorsal hooks and
      lateral spines. 

PMID- 24870651
TI  - Lanzavecchia mangrovi sp. n. (Nematoda, Dorylaimida) from mangroves of Red River
      Estuary, Vietnam.
AB  - A new nematode species found in the Red River Estuary of Vietnam is described.
      Lanzavecchia mangrovi sp. n. is morphologically close to L. coomansi Nicholas,
      Stewart, 1984, but differs in its longer body (L = 2.71-3.76 um versus L = 2.2
      2.9 um), shorter spicules (63-65 mm versus 72-88), longer prerectum (500-675 mm
      versus 262-310 um) and shorter distal portion of tail in relation to the proximal
      portion (0.6-0.8 versus 0.9-2.3).

PMID- 24870653
TI  - The genus Hylebainosoma Verhoeff, 1899 (Diplopoda, Chordeumatida, Haaseidae):
      redescription of Hylebainosoma tatranum, description of a new troglobiont species
      and notes to the Hylebainosoma-Romanosoma species group.
AB  - A revision of the taxonomy, distribution and ecology of the millipedes of the
      genus Hylebainosoma Verhoeff, 1899 in the Carpathians is presented. Based on the
      study of numerous specimens, we consider the subspecies of the species
      Hylebainosoma tatranum Verhoeff, 1899 described in the past as overrated,
      reflecting simply intrapopulational variation attributable to the rather extended
      area of species distribution, different habitats of its occurrence (surface and
      cave habitats, soil, litter and stony debris) and wide altitudinal range from the
      forest zone in foothills to the alpine zone above timberline. Besides the
      redescription of males, the morphology of female vulvae is presented for the
      first time. Hylebainosoma tatranum is endemic to the extensive area of the
      Western and Eastern Carpathians, involving Slovakia, Hungary, the Czech Republic,
      Poland and highly probably Ukraine. A new troglobiont species from the karst area
      near the Tisovec Town (Muranska planina Mts., Central Slovakia), Hylebainosoma
      gulickai n. sp. is described, and is considered as stenoendemic for this small
      karstic region, with occurrence in few nearby caves. Hylebainosoma gulickai
      represents the first troglobiont chordeumatid millipede found in the northern
      territories of the Carpathians and the northernmost troglobiont in Central Europe
      in general. Morphological characteristics of both males and females are
      presented.Taxonomic relationships between the closely related genera
      Hylebainosoma and Romanosoma Ceuca, 1967 are discussed and replacement of the
      species Hylebainosoma cavernicola (Ceuca, 1967) n. comb., Hylebainosoma oltenica
      (Ceuca, 1967) n. comb. and Hylebainosoma odici (Ceuca, 1979) n. comb. into the
      genus Hylebainosoma is proposed. The fourth species described as Romanosoma (?)
      birtei Ceuca, 1967 we consider as invalid taxon. Romanosoma becomes a junior
      subjective synonym of the genus Hylebainosoma.  

PMID- 24870652
TI  - A new species of Aricoris Westwood, [1851] belonging to "chilensis" group
      (Lepidoptera: Riodinidae).
AB  - A new species of Riodinidae from the grasslands of South Brazil, Paraguay and
      Argentina, Aricoris schneideri sp. nov., is described. 

PMID- 24870654
TI  - Aquatic tardigrades in the Great Smoky Mountains National Park, North Carolina
      and Tennessee, U.S.A., with the description of a new species of Thulinius
      (Tardigrada, Isohypsibiidae).
AB  - As part of the All Taxa Biodiversity Inventory (http://www.dlia.org), an
      extensive survey of tardigrades has been conducted in the Great Smoky Mountains
      National Park (GSMNP) in Tennessee and North Carolina, U.S.A., by Bartels and
      Nelson. Freshwater tardigrades include three species in the aquatic genus
      Thulinius (Eutardigrada, Isohypsibiidae). A new species, Thulinius romanoi,
      described from stream sediment, is distinguished from all other congeners by
      having a sculptured cuticle. In addition, the presence of Thulinius augusti
      (Murray, 1907) was verified by combined morphological and molecular analysis, and
      nine specimens of a third species, Thulinius cf. saltursus, were also found.
      Thulinius augusti is a new record for the United States. Thulinius saltursus
      (Schuster, Toftner & Grigarick, 1978) was previously recorded in California and
      Ohio, but our specimens vary slightly in morphology. The list of tardigrades from
      streams in the GSMNP was updated to a total of 44 species, 22 of which were
      predominantly or exclusively aquatic. 

PMID- 24870655
TI  - Three new species of the genus Paraleucilla Dendy, 1892 (Porifera, Calcarea) from
      the coast of Bahia State, Northeastern Brazil.
AB  - Three new species of calcareous sponges from the coast of Bahia State, NE Brazil
      are described. All of them belong to the genus Paraleucilla (Calcaronea,
      Leucosolenida, Amphoriscidae): P. solangeae sp. nov., P. oca sp. nov., and P.
      incomposita sp. nov. The number of species recorded from the Bahia coast has thus
      increased from 10 to 13. Including these new species, there are now 50 calcareous
      sponge species known from the entire Brazilian coast. Paraleucilla is now
      composed of 11 species, six of them occurring along the southwestern Atlantic
      Ocean. The remaining species occur mainly in the Indian Ocean, and also in the
      Pacific Ocean, Red Sea and Mediterranean Sea. An identification key for all
      Paraleucilla species is provided. This paper is dedicated to the memory of
      Professor Solange Peixinho, to acknowledge her contribution to our understanding
      of the biodiversity of Calcarea from the Bahia coast in Brazil. 

PMID- 24870656
TI  - New earthworm records from Turkey, with description of three new species
      (Oligochaeta: Lumbricidae).
AB  - Identifying the earthworm material recently collected in different parts of
      Turkey (Marmara Region, Upper Mesopotamia, Hatay Province and East Anatolia)
      resulted in records of 29 earthworm species including three lumbricids new to
      science: Dendrobaena cevdeti, D. szalokii and Eisenia patriciae spp. nov. In
      addition, Dendrobaena cognettii is reported for the first time from the country.
      With this contribution, the number of earthworm species and subspecies registered
      in Turkey is raised to 80. 

PMID- 24870658
TI  - A second new species of Tyrrhenoleuctra discovered by means of molecular data:
      Tyrrhenoleuctra lusohispanica n. sp. (Plecoptera: Leuctridae).
AB  - Tyrrhenoleuctra lusohispanica sp. n., a new species of the leuctrid genus
      Tyrrhenoleuctra from the southern Iberian Peninsula (southern Portugal and Spain)
      is described solely on molecular characters. Molecular analyses clearly indicated
      the distinctness of this species and demonstrated the presence of cryptic species
      in the genus Tyrrhenoleuctra. We also describe the systematic affinities of T.
      lusohispanica sp. n. to other species in the genus. With all Tyrrhenoleuctra
      species, T. lusohispanica sp. n. exhibits marked phenotypic variability. 

PMID- 24870657
TI  - A remarkable new genus of Tettigarctidae (Insecta, Hemiptera, Cicadoidea) from
      the Middle Jurassic of northeastern China.
AB  - Tianyuprosbole zhengi, a remarkable new genus and species of Tettigarctidae
      (Insecta, Hemiptera, Cicadoidea), is described based on a whole-bodied fossil
      from the Middle Jurassic of Daohugou, northeastern China. The new species
      possesses a tegmen similar to that of Cicadoprosbole, the type genus of
      Cicadoprosbolinae, and has an exceedingly expanded pronotum as the extant genus
      Tettigarcta. This specimen provides new insights in the evolution and taxonomy of
      tettigarctids. 

PMID- 24870659
TI  - Paraphyly-again!? A plea against the dissociation of taxonomy and phylogenetics.

PMID- 24870660
TI  - A new species of Lasinus Sharp (Coleoptera: Staphylinidae: Pselaphinae) from East
      China.
AB  - Lasinus orientalis Yin & Bekchiev, new species, is described from the eastern
      Chinese provinces of Zhejiang and Jiangxi, with major diagnostic features
      illustrated. The new species is compared with, and distinguished from related
      congeners. 

PMID- 24870661
TI  - Practice nurse involvement in general practice clinical care: policy and funding
      issues need resolution.
AB  - In Australia, primary care-based funding initiatives have been implemented to
      encourage general practices to employ practice nurses. The aim of this paper is
      to discuss limitations of the current funding and policy arrangements in
      enhancing the clinical role of practice nurses in the management of chronic
      conditions. This paper draws on the results of a real-world economic evaluation,
      the Primary Care Services Improvement Project (PCSIP). The PCSIP linked routinely
      collected clinical and resource use data to undertake a risk-adjusted cost
      effectiveness analysis of increased practice nurse involvement in clinical-based
      activities for the management of diabetes and obesity. The findings of the PCSIP
      suggested that the active involvement of practice nurses in collaborative
      clinical-based activities is cost-effective, as well as addressing general
      practice workforce issues. Although primary healthcare organisations (e.g.
      Medicare Locals) can play a key role in supporting enhanced practice nurse roles,
      improvements to practice nurse funding models could further encourage more
      efficient use of an important resource. 

PMID- 24870663
TI  - A review of the Palaearctic Mniotype adusta (Esper, 1790) species-group with
      description of a new species and six new subspecies (Lepidoptera: Noctuidae).
AB  - Eighteen Palaearctic taxa of the Mniotype adusta species-group are reviewed. One
      new species (M. kobyakovi Volynkin, Matov & Behounek, sp. n.) and six new
      subspecies (M. lama kortka Volynkin, Matov & Behounek, ssp. n., M. lama etugen
      Volynkin, Matov & Behounek, ssp. n., M. lama ayubaevorum Volynkin, Matov &
      Behounek, ssp. n., M. adusta poltavskyi Volynkin, Matov & Behounek, ssp. n., M.
      adjuncta cineritia Volynkin, Matov & Behounek, ssp. n. and M. dubiosa amitayus
      Volynkin & Han, ssp. n.) are described. Two taxa, previously regarded as
      subspecies are restored to specific status: M. adjuncta (Moore, 1881) stat. n.
      and M. dubiosa (A. Bang-Haas, 1912) stat. n. A taxon previously regarded as a
      junior synonym is restored to specific status: M. juldussica (Draudt, 1934) stat.
      n. A new synonymy is introduced: M. bathensis (Lutzau, 1900) = Hadena adusta var.
      moesta Staudinger, 1897 syn. n. The synonymy of M. bathensis and Crino adusta
      subsp. urupino Bryk, 1942 syn. rev. is revised. The lectotypes for Hadena? lama
      Staudinger, 1900, Mamestra vicina Alpheraky, 1882, Hadena adusta var. moesta
      Staudinger, 1897 and Hadena lama var. dubiosa A. Bang-Haas, 1912 are designated.
      The neotype for Crino adusta juldussica Draudt, 1934 is designated. The adults,
      male and female genitalia of all reviewed species and subspecies are illustrated.

PMID- 24870664
TI  - Mud-packing frog: a novel breeding behaviour and parental care in a stream
      dwelling new species of Nyctibatrachus (Amphibia, Anura, Nyctibatrachidae).
AB  - Reproductive modes are diverse and unique in anurans. Selective pressures of
      evolution, ecology and environment are attributed to such diverse reproductive
      modes. Globally forty different reproductive modes in anurans have been described
      to date. The genus Nyctibatrachus has been recently revised and belongs to an
      ancient lineage of frog families in the Western Ghats of India. Species of this
      genus are known to exhibit mountain associated clade endemism and novel breeding
      behaviours. The purpose of this study is to present unique reproductive
      behaviour, oviposition and parental care in a new species Nyctibatrachus kumbara
      sp. nov. which is described in the paper. Nyctibatrachus kumbara sp. nov. is a
      medium sized stream dwelling frog. It is distinct from the congeners based on a
      suite of morphological characters and substantially divergent in DNA sequences of
      the mitochondrial 16S rRNA gene. Males exhibit parental care by mud packing the
      egg clutch. Such parental care has so far not been described from any other frog
      species worldwide. Besides this, we emphasize that three co-occurring congeneric
      species of Nyctibatrachus, namely N. jog, N. kempholeyensis and Nyctibatrachus
      kumbara sp. nov. from the study site differ in breeding behaviour, which could
      represent a case of reproductive character displacement. These three species are
      distinct in their size, call pattern, reproductive behaviour, maximum number of
      eggs in a clutch, oviposition and parental care, which was evident from the
      statistical analysis. The study throws light on the reproductive behaviour of
      Nyctibatrachus kumbara sp. nov. and associated species to understand the
      evolution and adaptation of reproductive modes of anurans in general, and
      Nyctibatrachus in particular from the Western Ghats. 

PMID- 24870665
TI  - Delimiting the distribution range of Indirana leithii (Boulenger, 1888) (Anura:
      Ranixalidae), an endemic threatened anuran of the Western Ghats, based on
      molecular and morphological analysis.
AB  - Indirana leithii (Boulenger, 1888) (Anura: Ranixalidae) is a frog species endemic
      to the Western Ghats and is categorized as Vulnerable according to IUCN red list.
      This species is currently considered to be widespread over the entire Western
      Ghats. Our study based on molecular data (using DNA sequence fragments of the
      mitochondrial 12S rRNA and 16S rRNA genes and the nuclear rhodopsin gene),
      morphological analysis of topotypic material as well as material collected from a
      wide range within the northern Western Ghats, suggests that the species has
      instead a restricted range in the state of Maharashtra. Specimens identified as
      I. leithii from the southern Western Ghats as well as from outside the Western
      Ghats probably belong to hitherto undescribed species. To facilitate future
      studies in understanding the nature of this species complex and provide better
      means for identification and delimitation of species we provide molecular,
      morphological and osteological characters of I. leithii from topotyic material. 

PMID- 24870666
TI  - Molecular parataxonomy as taxon description: examples from recently named
      Zoanthidea (Cnidaria: Anthozoa) with revision based on serial histology of
      microanatomy.
AB  - Current taxonomic practices require corroboration from multiple lines of evidence
      to provide sufficient rigor for species discovery and description. However, many
      recently named taxa (species-families) are defined by nucleotide sequence with
      little or no description of the features that traditionally define higher taxa
      and link nucleotide-based information to the existing taxonomic system. Without
      knowledge of form, it may be impossible to identify conspecifics, congeners, and
      confamiliars of new taxa among the hundreds of specimens and described species
      for which nucleotide sequencing is not now, and may never be, available.
      Additionally, some nucleotide sequences are invariant or inconsistently
      differentiated between congeners; severely limiting the utility of nucleotide
      based taxon definitions. Here we use serial histology of paratypes to reveal the
      microanatomy of internal structures and revise the definitions of the Zoanthidea
      taxa Corallizoanthus tsukaharai Reimer, Antipathozoanthus hickmani Reimer &
      Fujii, Parazoanthus darwini Reimer & Fujii, Terrazoanthus onoi Reimer & Fujii,
      Terrazoanthus sinnigeri Reimer & Fujii, Microzoanthus kagerou Fujii & Reimer, and
      Zoanthus kuroshio Reimer & Ono; examination of Mesozoanthus lilkweminensis Reimer
      & Sinniger failed to produce interpretable sections. The results described here,
      with individual measurements documented in Morphbank (collection 829724) and
      Encyclopedia of Life (by taxon name), indicate a notably rich diversity of form
      for an order that is often characterized as depauperate in morphological
      diversity. One prominent example is a novel marginal muscle structure (cyclically
      transitional) that is not observable without serial sections. These findings may
      renew interest in morphological characters and provide the foundation for
      revision of Zoanthidea higher taxa, particularly now that phylogenetic
      relationships for these taxa can be inferred. 

PMID- 24870667
TI  - A new species of Tityus (Scorpiones, Buthidae) from El Eden Cave, Colombia.
AB  - A new scorpion species, Tityus (Tityus) grottoedensis sp. nov., is herein
      described based on male and female specimens collected in El Eden Cave and its
      vicinities (Tolima department, Colombia). The new species, which becomes the
      first scorpion described from a Colombian cave, is probably a eutroglophile or
      subtroglophile element; however, additional studies are needed to determine the
      degree of association of the species to the cave. Among other features, the new
      species is characterized by having a relatively thin body, a yellow-to-chestnut
      coloration, sternites IV to VI with visible lateral longitudinal carinae, and the
      basal piece of the middle lamella of the pectines dilated in male and female. 

PMID- 24870668
TI  - A synopsis of the Neotropical genus Nephepeltia (Odonata: Libellulidae),
      including description of a new species, synonymies, and a key to males.
AB  - Nephepeltia flavipennis (Holotype: Brazil, Rondonia, Governador Jorge Teixeira
      Municipality, Fazenda Rancho Grande, 10 degrees 31'48''S, 62 degrees 48'0''W, 165
      m, J. Wiseman leg., in MNRJ) is described from the Amazon region of W Brazil,
      Ecuador, and N Peru. A lectotype is designated for N. aequisetis Calvert, 1909.
      Nephepeltia chalconota is considered to be a junior subjective synonym of N.
      flavifrons Karsch, 1889, and the subdivision of N. phryne into two subspecies is
      found to be unjustifiable. Diagnoses, illustrations, a key to males, and an
      updated map for all known members of the genus are provided. 

PMID- 24870669
TI  - Three new species of the genus Loxoconcha (Crustacea, Ostracoda, Podocopida) from
      the Okinawa Islands, southern Japan.
AB  - Three new species of Ostracoda, Loxoconcha noharai sp. nov., L. santosi sp. nov.
      and L. sesokoensis sp. nov., are described from the Okinawa Islands, southern
      Japan. The two species Loxoconcha noharai sp. nov. and L. santosi sp. nov. live
      in estuaries, whereas the species L. sesokoensis sp. nov. lives in coral reefs.
      These species can be easily distinguished from other previously described
      Loxoconcha species by their morphological differences, mainly in the male
      copulatory organ, and distribution pattern of their pore systems. In addition, L.
      sesokoensis sp. nov. is suggested to be phylogenetically apart from any other
      Loxoconcha species which have been reported so far from Japan and the adjacent
      seas. 

PMID- 24870670
TI  - Biodiversity and bionomics of the black flies (Diptera: simuliidae) of
      northeastern Algeria.
AB  - Black flies in the Seybouse River Basin in northeastern Algeria were sampled at
      31 sites along the main river and its tributaries across all seasons from 2011 to
      2013. Eight nominal species and species complexes in three genera were identified
      among more than 31,000 specimens. Urosimulium faurei (Bernard, Grenier & Bailly
      Choumara), Simulium (Eusimulium) mellah Giudicelli & Bouzidi, and Simulium
      (Nevermania) lundstromi (Enderlein) were recorded for the first time in
      northeastern Algeria. Three cytoforms of the Simulium (Eusimulium) velutinum
      complex and two morphoforms of Simulium (Nevermannia) ruficorne Macquart were
      found. The most abundant and ubiquitous taxon, Simulium (Wilhelmia) pseudequinum
      Seguy, representing nearly 80% of collected specimens, occupied the widest range
      of habitats, including those with anthropogenic influences. 

PMID- 24870671
TI  - A new species of broad-nosed bat Platyrrhinus Saussure, 1860 (Chiroptera:  
      Phyllostomidae) from the Guianan Shield.
AB  - A new species of broad-nosed bat Platyrrhinus Saussure, 1860 (Chiroptera:
      Phyllostomidae: Stenodermatinae) from the Guianan Shield is described based on
      molecular and morphological data. Previously confused with P. helleri and P.
      recifinus, the new taxon is currently known from only Guyana and Suriname and is
      most closely related to P. recifinus from eastern Brazil and not to the two
      sympatric species (P. fusciventris and P. incarum) also recently recognized as
      distinct from P. helleri. Morphometrically the new taxon overlaps with the
      smaller species of the genus (P. angustirostris, P. brachycephalus, P.
      fusciventris, P. helleri, P. incarum, and P. matapalensis), but forms a different
      cluster from the larger P. recifinus. Morphologically the new taxon is
      distinguished from its congeners by a combination of external and craniodental
      characteristics. Platyrrhinus now includes 21 species making it the most speciose
      genus in the Neotropical family Phyllostomidae. 

PMID- 24870672
TI  - Re-description of Medetera glaucella Kowarz, 1878 (Diptera, Dolichopodidae) based
      on type material.

PMID- 24870673
TI  - A new species of Aspidimorpha (Coleoptera: Chrysomelidae: Cassidinae:
      Aspidimorphini) from Uganda.
AB  - Aspidimorpha (Aspidimorpha) wagneri sp. nov. is described from Uganda. This
      species belongs to the nominotypical subgenus, together with several African
      species that are closely related to A. mutata Boheman, 1854. Its relative
      position within the genus is discussed. 

PMID- 24870674
TI  - A new mountain lizard from Montes de Leon (NW Iberian Peninsula): Iberolacerta
      monticola astur ssp. nov. (Squamata: Lacertidae).
AB  - Iberolacerta populations from the Northern Montes de Leon (NML) were studied by
      means of external morphology (scalation and biometry), osteology and genetics
      (mtDNA and microsatellites), searching for their homogeneity
      ("intrazonalanalysis") and, once verified, comparing them with Iberolacerta
      monticola s. str. (from Central Cantabrian Mountains)and/. gal ani (from Southern
      Montes de Leon) ("extrazonal analysis") from neighboring areas.Our "intrazonal
      analysis" revealed discordances between the different approaches, especially the
      patterns of variation of nuclear microsatellites (congruent with external
      morphology) and mtDNA, namely a very low nuclear differentiation between
      relatively highly differentiated mtDNA lineages. The morphological approach was
      unable to discriminate any of the populations as significantly different from the
      others in the NML. Mitochondrial DNA revealed a haplotype lineage closely related
      to I. galani (MNL-II in our text) in some specimens of Sierra de Villabandfn and
      Suspiron, but these populations are morphologically indistinguishable from the
      main part of the other populations that belong to lineage NML-1,phylogenetically
      closer to/. monticola. After a separation from I. manti cola ca. 1.8 Mya, the
      populations in this geographic region must have suffered at least two different
      waves of gene flow from I. gal ani, the second one not much later than 0.5 Mya.
      Microsatellite results indicate that all the NML populations are genetically
      similar in terms of their nuclear genomes,independently of their mitochondrial
      differentiation (NML-I vs. NML-II haplotype groups). Since all the morphological
      and microsatellite evidences point towards the fact that, independently of the
      mitochondrial haplotypes that they bear (NML-1 or NML-II), there is only one
      taxon in the area, we describe it as: Iberolacerta monticola astur ssp.
      nov.Concerning the relationships of I. m. astur ssp. nov. with I. monticola s.
      str. and I. gal ani ("extra zonal analysis"), in the female analyses the new
      taxon centroid is closer to I. monticola s. str. than to I. gal ani (more
      similarity with I manticolas.str.), whereas in the male analyses the relationship
      is just the contrary (closer to I. gal ani, paralleling the direction of the
      hypothesized past hybridization). Moreover, in both sexes' ANOVA, I. m. astur
      ssp. nov. results more similar (lessP<0.05 differences) to I. galani than to I.
      monticola s. str. Osteologically, I. m. astur ssp. nov. is slightly more similar
      toI. monticola s. str. than to I. galani, especially in the squamosal bone, which
      is regularly arched (primitive shape). Genetically,as indicated above, the NML
      populations can be subdivided in two groups according to their mitochondrial
      DNA,namely NML-I (bearing clearly differentiated haplotypes, phylogenetically
      closer to I. monticola) and NML-II (whose haplotypes could have been mistaken for
      those of an I. gal ani population). This mitochondrial subdivision has at most a
      subtle nuclear correlate, however. According to the nuclear microsatellite
      markers, all the NML populations belong to a single group(/. m. astur ssp. nov.),
      which would be more similar to I. gal ani than to I monticola, with NML-II
      populations lying closer to I. galani than those from the NML-I group and,
      correspondingly, more distant from I. monticola. The discordant phylogenetic
      signal of mitochondrial and nuclear markers is discussed in terms of past
      introgression events and sex-biases in phylopatry and dispersion in these
      species. Iberolacerta manti cola astur ssp. nov., inhabits the Northern Montes de
      Leon (Sierra de Gistreo sensu latissimo ): Gistredo,Catoute, Tambaron, Nevadfn,
      Villabandfn (or Macizo del Alto de Ia Canada), Arcos del Agua (or Fernan
      Perez),Tiendas and Suspiron, mainly in quartzite and slate rock substrates. Its
      current distribution, cornered in the NW of theNorthern part of the Montes de
      Leon, suggests a possible competitive exclusion between this taxon and/. galani,
      as the galani haplotypes (NML-II) appear cornered in the most harsh and
      continental areas, speaking also about a, even in the past, very limited presence
      of this species in the area that probably was soon absorbed by I. m. astur ssp.
      nov. (with NMLI haplotypes). Variation in watershed limits (especially with l
      montico/a s. str. in the North) and Pleistocene climatic oscillations(with I. gal
      ani in the South) probably played a crucial role in isolation of the different
      Iberolacerta colonizationwaves in this zone. These changes in the boundaries
      among watersheds limited the contact between the NML and the main Cantabrian
      Mountains, restricting to narrow points (different along time) the contact
      between the two ranges, and thus,the areas for possible contact between I. m.
      astur ssp. nov. and I. monticola s. str. (see Fig. lB). The origin of this tax on
      dates back to the end of Pliocene or Lower Pleistocene (around 1.8 Mya),
      according to mtDNA divergence. On the other side, climatic oscillations allowed
      expansion and contact with the more continental harsh climate-dwelling I. gal
      ani.

PMID- 24870675
TI  - The ANDEEP Tanaidacea (Crustacea: Peracarida) revisited III: the family
      Akanthophoreidae.
AB  - A restricted phylogenetic analysis is conducted to test if the family
      Akanthophoreidae is monophyletic. The family was found to be monophyletic with a
      Bremer support of 11 and is redefined to include the genera Akanthophoreus,
      Chauliopleona, Mimicarhaphura, Parakanthophoreus gen. nov., Paraleptognathia,
      Stenotanais, and Tumidochelia, while Gejavis is removed. Akanthophoreus and
      Paraleptognathia are redefined and now consist of only four and two species
      respectively. The remaining species previously assigned to these genera are
      transferred to a new genus Parakanthophoreus. A key to the genera of the family
      is presented. Two new species of Chauliopleona, C. ciimari and C. andeepi, and
      one of Parakanthophoreus, P. greenwichius, are described from the ANDEEP I-III
      and ANDEEP-SYSTCO material.  

PMID- 24870676
TI  - Review of the genus Thliptoceras Warren, 1890 (Lepidoptera: Crambidae:
      Pyraustinae) from the Oriental region of China.
AB  - The species of the genus Thliptoceras Warren, 1890 from the Oriental region of
      China are reviewed, and a description of the genus is given. Five new species, T.
      bicuspidatum sp. nov., T. semicirculare sp. nov., T. bisulciforme sp. nov., T.
      filamentosum sp. nov. and T. impube sp. nov. are described. T. fulvimargo
      (Warren, 1895) is newly recorded for China. A key to the species of the Oriental
      region of China is provided, along with diagnoses for previously described
      species. Illustrations of external features and genitalia are presented. 

PMID- 24870677
TI  - The larvae of European Ascalaphidae (Neuroptera).
AB  - The larvae of all the European genera of Ascalaphidae are compared for the first
      time, highlighting the differential characters for identification purposes. The
      larva of the genus Ascalaphus is described for the first time while those of
      Puer, Bubopsis and Deleproctophylla are deeply revised. Actually, the larvae of
      Ascalaphus festivus (Rambur), Puer maculatus (Olivier), Bubopsis agrionoides
      (Rambur), Deleproctophylla australis (Rambur), Libelloides latinus (Lefebvre),
      Libelloides corsicus (Rambur) and Libelloides siculus (Angelini) are described or
      accurately depicted for the first time. The known larvae of the genus Libelloides
      are reviewed. 

PMID- 24870678
TI  - Revision of the Megaloptera (Insecta: Neuropterida) of Madagascar.
AB  - The Megaloptera fauna of Madagascar comprise two endemic genera: Haplosialis
      Navas, 1927 (Sialidae) and Madachauliodes Paulian, 1951 (Corydalidae:
      Chauliodinae). Here the two genera are revised, with detailed descriptions and
      illustrations. A new species, Madachauliodes bicuspidatus Liu, Price & Hayashi,
      sp. nov., is described. Furthermore the phylogeny and biogeography of the
      Madagascan fauna is discussed. 

PMID- 24870679
TI  - Three new species of Protearomyia McAlpine, 1962 (Diptera: Lonchaeidae) with a
      key to males of the Palearctic species.
AB  - Three new species of Palearctic Protearomyia McAlpine, 1962 are described, P.
      iberica sp. nov., P. rameli sp. nov. and P. withersi sp. nov. These are compared
      with the three previously described species, a key is provided to the males of
      all the Palearctic species. 

PMID- 24870680
TI  - A new European species of Nevrorthus in the Iberian Peninsula(Insecta,
      Neuropterida).
AB  - A new species of Nevrorthus (Insecta, Neuropterida: Nevrorthidae) has been found
      in the south of the Iberian Peninsula (Spain, Malaga): N. reconditus Monserrat &
      Gavira n. sp. This new species represents the first record of this genus and this
      family in the Westernmost Mediterranean basin. A key to the known species of this
      genus is provided. 

PMID- 24870681
TI  - Myrmecophilous rove beetles (Coleoptera: Staphylinidae) associated with Aenictus
      hodgsoni (Hymenoptera: Formicidae) from Thailand, with description of two new
      genera and three new species.
AB  - Three species of rove beetles (subfamily Aleocharinae) were collected from
      colonies of Aenictus hodgsoni Forel, 1901 in Khao Yai National Park, Thailand.
      They are classified into three genera, including two new genera, and described
      herein as: Aenictobia siamensis Maruyama, sp. n. (tribe Aenictoteratini),
      Aenictosymbia cornuta Maruyama, gen. & sp. n. (tribe Lomechusini) and
      Aenictoxenides mirabilis Maruyama, gen. & sp. n. (tribe Pygostenini). The
      systematic positions of the new genera are discussed. 

PMID- 24870682
TI  - Taxonomy of European Damaeidae (Acari: Oribatida) VII. Redescription of Neobelba
      pseudopapillipes Bulanova-Zachvatkina, 1967 with comments on its generic status.
AB  - We redescribe Neobelba pseudopapillipes Bulanova-Zachvatkina, 1967, single known
      species of Neobelba Bulanova-Zachvatkina, 1967, based on the material collected
      in Russia and Slovakia. The species shares many important characters of Metabelba
      Grandjean, 1936, particularly of the subgenus M. (Pateribelba) Mourek, Miko et
      Bernini, 2011. It can be easily distinguished by presence of companion seta d,
      coupled with solenidion on tibia IV. As the original material of Bulanova
      Zachvatkina was lost, neotype and 14 paraneotypes from Voronezh region, Russia
      are newly designated. Based on the neotype redescription, Neobelba was re-defined
      and the new status was proposed. Synonymy with Metabelba s. str. as proposed by
      Subias (2013) is rejected, and Neobelba is considered to be a separate subgenus
      of Metabelba, as earlier proposed by Subias (2004). Present distribution of
      Metabelba (Neobelba) pseudopapillipes (Bulanova-Zachvatkina, 1967) and known
      ecological data on the species are provided.

PMID- 24870683
TI  - First record of the family Ithonidae (Neuroptera) from Baltic amber.
AB  - Elektrithone expectata gen. et sp. nov. (Neuroptera: Ithonidae) is described from
      Eocene Baltic amber and represents the first record of this family from Baltic
      amber. The forewing venation of the new genus is characterized by a small number
      of crossveins as found in some 'polystoechotid'-like genera, and by the absence
      of the distal nygma and the strong reduction of the anal area which are
      characteristic of 'rapismatid'-like ithonids. 

PMID- 24870684
TI  - Notes on two species of the cavernicolous subgenus Neobisium (Blothrus) Schiodte,
      1847 (Arachnida: Pseudoscorpiones) from Transylvania (Romania), with a key to the
      species of the Carpathian Mountains.
AB  - Redescriptions of Neobisium (Blothrus) minutum (Tomosvary, 1882) and N. (B.)
      brevipes (Frivaldszky, 1865) are given, accompanied by new illustrations.
      Neobisium (B.) brevipes montanum is elevated to full species rank as N. (B.)
      montanum Beier, 1939. New records of N. (B.) minutum and N. (B.) brevipes from
      Romania are presented. A key to the members of the subgenus Blothrus occurring in
      the Carpathian Mountains is provided. 

PMID- 24870685
TI  - Two new species of Kalophrynus Tschudi, 1838 (Anura: Microhylidae) from the
      Annamite mountains in southern Vietnam.
AB  - We describe two new mountain-dwelling microhylid species of the genus Kalophrynus
      from the southern part of the Annamite Mountains in Vietnam. The two new species
      differ from all known congeners in morphological characters and mtDNA;
      phylogenetically, they form a sister clade to the large-bodied K. interlineatus
      (1009 bp, 16S rRNA gene, mtDNA). Both species share the following
      characteristics: snout pointed in dorsal and lateral views, slightly sloping in
      profile; tympanum distinct, smaller than eye in diameter; toe webbing moderate;
      outer metatarsal tubercle present; light dorsolateral line absent. Kalophrynus
      cryptophonus sp. nov. from Loc Bao, Lam Dong Province is a small-sized species
      distinguishing from its congeners by a combination of: SVL 27.9-30.4 mm in males,
      23.4 mm in female; canthus rostralis indistinct; males with large sharp conical
      spines on the skin covering mandible margins and finely asperous nuptial pads on
      the dorsal surface of fingers I-III; dark ocelli in the inguinal region usually
      present, small, without a light border; anterior palatal dermal ridge short,
      restricted to medial part of palate. Kalophrynus honbaensis sp. nov. from Hon Ba,
      Khanh Hoa Province is a medium-sized Kalophrynus, distinguishing from its
      congeners by a combination of: SVL 26.7-36.8 mm in males; canthus rostralis
      distinct; males without distinguishable spines on the mandible margins nor the
      nuptial pads; dark ocelli in the inguinal region present, large, without a
      distinct light border, anterior palatal dermal ridge developed, parallel to
      posterior one. Kalophrynus cryptophonus sp. nov. reproduces in hollow bamboo
      stems; we describe larval morphology and bioacoustics of this species in relation
      to phytotelm breeding. A review of the distribution of the genus Kalophrynus in
      Indochina is provided. 

PMID- 24870686
TI  - Australia's deep-water octocoral fauna: historical account and checklist,
      distributions and regional affinities of recent collections.
AB  - The number of deep-water (>80 m) octocoral species recorded from Australian
      waters has more than tripled from 135 to 457 following six surveys undertaken
      between 1997 and 2008 on the deep continental margin of south-eastern, western
      and north-western Australia and the Tasman Sea.  This rapid increase in knowledge
      follows a slow accumulation of records since the earliest collections were made
      by vessels such as the Geographe and the Naturaliste in the early years of the 19
      century. Consistent identification and alpha-labelling of the octocoral fauna
      between surveys has permitted a multi-region description and comparison.  We
      detail the identities, distributions and regional affinities of 457 octocoral
      species in 131 genera and 28 families from the orders Alcyonacea and
      Pennatulacea, including 69 new species, 17 new genera and 43 first records for
      Australia. Five of the more common genera were widely distributed (present at 35
      and 66 sampling stations spanning all of the 4 survey regions), but two were
      restricted to south-eastern Australia-Pleurogorgia Versluys, 1902 and Tokoprymno
      Bayer, 1996-and were only sampled from depths below 700 m.  The great majority of
      species (81%) and nearly half of all genera (47%) were only sampled once or
      twice.  The highest average number of species per sampling station (3.2) was
      reported from the outer shelf. The proportion of new species was highest (22%) on
      the upper and lower slope bathomes, intermediate (13-15%) on the mid-slope
      bathome and lowest (8%) on the outer shelf bathome.  Species overlap between
      bathomes was low, but all families were shared across bathomes. Most described
      species (55 of 69) have an Indo-West Pacific affinity, 20 have an Indian Ocean
      affinity, while three were previously recorded from the Atlantic Ocean only; 20
      appear to be Australian endemics. Octocorals can now be added to an emerging set
      of taxon-specific data sets-including fishes, ophiuroids and galatheids-that
      permit regional-scale analysis of biodiversity distributions to support
      Australia's efforts in marine conservation management. However, because so much
      of the world octocoral literature is inadequate for accurate identifications to
      species level, there is a pressing need for taxonomic revisions using modern
      morphological and molecular techniques to fine-tune the current use of octocorals
      as indicators of vulnerable marine ecosystems in many national and high seas
      conservation initiatives. 

PMID- 24870687
TI  - World catalog of extant and fossil Corethrellidae (Diptera).
AB  - A world catalog of extant and fossil frog-biting midges (Diptera: Corethrellidae)
      provides full type information, known life stages, and distribution of each
      species. There are 105 extant and seven fossil species of Corethrellidae but
      unnamed species are known from Costa Rica, Colombia and Madagascar. New
      information on types and other important specimens are provided. 

PMID- 24870688
TI  - World catalog of extant and fossil Chaoboridae (Diptera).
AB  - A world catalog of extant and fossil Chaoboridae provides full type information,
      distribution of each species, references to keys, references to latest
      descriptions of each species, and summaries of bionomic information.  There are
      51 extant species in six genera and 41 fossil species (2 unplaced) in 19 genera,
      two of which are extant. Chaoborus lanei (Belkin, Heinemann & Page) is a new
      synonym of C. braziliensis (Theobald) and C. annulatus Cook is a new synonym of
      C. festivus Dyar & Shannon. 

PMID- 24870689
TI  - Podocoryna loyola, n. sp. (Hydrozoa, Hydractiniidae): a probably introduced
      species on artificial substrate from southern Brazil.
AB  - Podocoryna loyola, a new hydractiniid species, has been found on artificial
      substrates in Baia de Paranagua, southern coast of Brazil, since April 2007. Its
      main morphological characteristics are: (1) polymorphic colonies with reticular
      stolons or encrusting hydrorhiza not covered by periderm and smooth chitinous
      spines; (2) newly-released medusae with eight tentacles and small interradial
      gonads; (3) mature medusae with eight tentacles and unbranched oral lips; gastric
      peduncle absent. Molecular data show that P. loyola is distinct from all other
      examined species of Podocoryna, and from P. hayamaensis Hirohito (1988), its
      sister species from Japan. As the polyps having been noted only quite recently,
      and in having been found only on man-made objects in port areas and estuaries,
      the species is most likely exotic to the region. 

PMID- 24870690
TI  - A revision of the bathyal and abyssal necrophage genus Cyclocaris Stebbing, 1888
      (Crustacea: Amphipoda: Cyclocaridae) with the addition of two new species from
      the Atlantic Ocean.
AB  - Two new species of the deep-sea scavenging genus Cyclocaris (Crustacea:
      Amphipoda) are described from bathyal and abyssal depths in the North and
      tropical Atlantic Ocean, bringing the total number of species in the genus to
      four. An account of all four species is given and an updated key to the genus
      Cyclocaris is provided. 

PMID- 24870691
TI  - Three new species of chewing lice of the genus Emersoniella Tendeiro, 1965
      (Insecta: Phthiraptera: Ischnocera: Philopteridae) from Papua New Guinean
      kingfishers and kookaburras (Aves: Coraciiformes: Alcedinidae).
AB  - Three new species of the ischnoceran louse genus Emersoniella (Phthiraptera) are
      described from four species of New Guinean kingfishers and kookaburras
      (Coraciiformes: Alcedinidae: Halcyoninae). They are: Emersoniella crassicarina n.
      sp. ex Dacelo gaudichaud Quoy & Gaimard (rufous-bellied kookaburra) and Dacelo
      leachii intermedia Salvadori (blue-winged kookaburra); E. reninoda n. sp. ex
      Melidora macrorrhina macrorhina Lesson (hook-billed kingfisher); and E. persei n.
      sp. ex Tanysiptera danae Sharpe (brown-headed paradise-kingfisher). In addition,
      we illustrate Emersoniella regis Emerson & Price, Emersoniella halcyonis
      Tendeiro, and the male genitalia of Emersoniella galateae Emerson & Price, as
      well as provide a complete host-louse checklist, and an updated key to all seven
      species of this genus.  

PMID- 24870692
TI  - Five new species of Camelobaetidius Demoulin, 1966 (Ephemeroptera: Baetidae), and
      redescription of Camelobaetidius mexicanus (Traver & Edmunds, 1968).
AB  - The genus Camelobaetidius Demoulin, 1966 has 38 species distributed throughout
      the Neotropical Region, being one of the most studied genera of the family
      Baetidae. Based on material from Brazil, the aim of the present paper is to
      describe five new species of Camelobaetidius with the terminal filament as long
      as cerci, and to redescribe the nymph of C. mexicanus (Traver & Edmunds, 1968)
      based on a paratype from Mexico. 

PMID- 24870693
TI  - Description of Cephalotes specularis n. sp. (Formicidae: Myrmicinae)-the mirror
      turtle ant.
AB  - We describe here Cephalotes specularis n. sp. (Hymenoptera: Formicidae:
      Myrmicinae: Cephalotini) based on minor and major workers, gynes and larvae from
      Uberlandia, Minas Gerais state, Brazil. On morphological and molecular grounds,
      this new species belongs to the C. fiebrigi + C. bruchi species complex, of which
      there are 11 previously described species (one in C. bruchi group and 10 in the
      C. fiebrigi group). All members of these groups are found in, or are limited to
      the South American "arid diagonal", comprised of the Argentinian Chaco, the
      Cerrados of central South America, and the Brazilian northeastern caatingas.
      Workers of C. specularis n. sp. have an extremely shiny gaster which is mirror
      like, notwithstanding its sparse covering by minute hairs. This species engages
      in a form of resource-based social parasitism of the host ant Crematogaster ampla
      (Myrmicinae: Crematogastrini). Cephalotes specularis foragers move freely in the
      dense traffic of Crematogaster ampla foraging trails. They exhibit highly
      atypical body posturing for turtle ants, which makes them hard to distinguish
      from the Crematogaster foragers. 

PMID- 24870694
TI  - Seven new species of Chimarra (Trichoptera: Philopotamidae) from Malawi.
AB  - For the first time species of caddisflies in the genus Chimarra Stephens 1829 are
      reported from Malawi. The following new species are described: Chimarra
      zombaensis, C. flaviseta, C. chichewa, C. circumverta, C. mulanjae, C. psittacus
      and C. calidopectoris. The descriptions add to the knowledge of Afrotropical
      diversity in the order Trichoptera. 

PMID- 24870696
TI  - Fabrication of large-sized two-dimensional ordered surface array with well
      controlled structure via colloidal particle lithography.
AB  - Epoxy resin coated glass slides were used for colloidal particle lithography, in
      order to prepare well-defined 2D surface arrays. Upon the assistance of a large
      sized 2D colloidal single crystal as template, centimeter-sized ordered surface
      arrays of bowl-like units were obtained. Systematic studies revealed that the
      parameters of obtained surface arrays could be readily controlled by some
      operational factors, such as temperature, epoxy resin layer thickness, and
      template particle size. With epoxy resin substituting for normal linear polymer,
      the height/diameter ratio of bowls in the formed surface arrays can be largely
      increased. With further reactive plasma etching, the parameters of ordered
      surface arrays could be finely tuned through controlling etching time. This study
      provides a facile way to prepare large-sized 2D surface arrays with tunable
      parameters. 

PMID- 24870697
TI  - Postprandial inflammation is not associated with endoplasmic reticulum stress in
      peripheral blood mononuclear cells from healthy lean men.
AB  - The consumption of lipids and simple sugars induces an inflammatory response
      whose exact molecular trigger remains elusive. The aims of the present study were
      to investigate (1) whether inflammation induced by a single high-energy, high-fat
      meal (HFM) is associated with endoplasmic reticulum stress (ERS) in peripheral
      blood mononuclear cells (PBMC) and (2) whether these inflammatory and ERS
      responses could be prevented by the chemical chaperone ursodeoxycholic acid
      (UDCA). A total of ten healthy lean men were recruited to a randomised, blind,
      cross-over trial. Subjects were given two doses of placebo (lactose) or UDCA
      before the consumption of a HFM (6151 kJ; 47.4 % lipids). Blood was collected at
      baseline and 4 h after the HFM challenge. Cell populations and their activation
      were analysed using flow cytometry, and plasma levels of inflammatory cytokines
      were assessed by ELISA and Luminex technology. Gene expression levels of
      inflammatory and ERS markers were analysed in CD14+ and CD14- PBMC using
      quantitative RT-PCR. The HFM induced an increase in the mRNA expression levels of
      pro-inflammatory cytokines (IL-1beta, 2.1-fold; IL-8, 2.4-fold; TNF-alpha, 1.4
      fold; monocyte chemoattractant protein 1, 2.1-fold) and a decrease in the
      expression levels of miR181 (0.8-fold) in CD14+ monocytes. The HFM challenge did
      not up-regulate the expression of ERS markers (XBP1, HSPA5, EDEM1, DNAJC3 and
      ATF4) in either CD14+ or CD14- cell populations, except for ATF3 (2.3-fold). The
      administration of UDCA before the consumption of the HFM did not alter the HFM
      induced change in the expression levels of ERS or inflammatory markers. In
      conclusion, HFM-induced inflammation detectable on the level of gene expression
      in PBMC was not associated with the concomitant increase in the expression levels
      of ERS markers and could not be prevented by UDCA.

PMID- 24870698
TI  - Transarterial chemoembolization for hepatocellular carcinoma with a new
      generation of beads: clinical-radiological outcomes and safety profile.
AB  - PURPOSE: To evaluate the short-term safety and efficacy of the new generation of
      70-150 um drug-eluting beads (M1 DEB) in patients with hepatocellular carcinoma
      undergoing transarterial chemoembolization (TACE) as a primary therapy or as a
      bridge to liver transplantation (LT). METHODS: Forty-five consecutive patients
      underwent TACE with M1 DEB loaded with doxorubicin (DEBDOX/M1). Clinical data
      were recorded at 12, 24, and 48 h, 7 and 30 days after treatment. Response was
      assessed by computed tomographic scan according to the modified response
      evaluation criteria in solid tumors criteria, and a second DEBDOX/M1 TACE was
      scheduled within 6 weeks in case of a noncomplete response. RESULTS: All patients
      had well-compensated cirrhosis (97.7 % Child A, 44.4 % hepatitis C virus, median
      age 61 years). Twenty patients (44.4 %) had Barcelona Clinic for Liver Cancer
      class B disease; the median number of nodules and their sum of diameters were 2
      (range 1-6) and 43 mm (range 10-190), respectively. The mean number of TACE
      procedures per patient was 1.4. Objective response rate (complete + partial
      response) was 77.7 % with a median time to best response of 3 months (95 %
      confidence interval 2-4). In 13 patients, DEBDOX/M1 TACE served as a
      bridge/downstaging to LT/surgery. Pathology showed that more than 90 % necrosis
      was achieved in 10 of 28 nodules. DEBDOX/M1 TACE was well tolerated, and the
      grade 3/4 adverse event rate was low (1 of 65 procedures). CONCLUSION: DEBDOX/M1
      TACE is an effective procedure with a favorable safety profile and promising
      results in terms of objective response rate, tumor downstaging, and necrosis.

PMID- 24870699
TI  - Seventeen years' experience of late open surgical conversion after failed
      endovascular abdominal aortic aneurysm repair with 13 variant devices.
AB  - PURPOSE: To investigate the causes and results of late open surgical conversion
      (LOSC) after failed abdominal aortic aneurysm repair (EVAR) and to summarize our
      17 years' experience with 13 various endografts. METHODS: Retrospective data from
      August 1994 to January 2011 were analyzed at our center. The various devices'
      implant time, the types of devices, the rates and causes of LOSC, and the
      procedures and results of LOSC were analyzed and evaluated. RESULTS: A total of
      1729 endovascular aneurysm repairs were performed in our single center (Nuremberg
      South Hospital) with 13 various devices within 17 years. The median follow-up
      period was 51 months (range 9-119 months). Among them, 77 patients with
      infrarenal abdominal aortic aneurysms received LOSC. The LOSC rate was 4.5 % (77
      of 1729). The LOSC rates were significantly different before and after January
      2002 (p < 0.001). The reasons of LOSC were mainly large type I endoleaks (n = 51)
      that were hard to repair by endovascular techniques. For the LOSC procedure, 71
      cases were elective and 6 were emergent. The perioperative mortality was 5.2 % (4
      of 77): 1 was elective (due to septic shock) and 3 were urgent (due to
      hemorrhagic shock). CONCLUSION: Large type I endoleaks were the main reasons for
      LOSC. The improvement of devices and operators' experience may decrease the LOSC
      rate. Urgent LOSC resulted in a high mortality rate, while selective LOSC was
      relatively safe with significantly lower mortality rate. Early intervention, full
      preparation, and timely LOSC are important for patients who require LOSC.

PMID- 24870700
TI  - CT-guided irreversible electroporation in an acute porcine liver model: effect of
      previous transarterial iodized oil tissue marking on technical parameters, 3D
      computed tomographic rendering of the electroporation zone, and histopathology.
AB  - PURPOSE: To evaluate the effect of previous transarterial iodized oil tissue
      marking (ITM) on technical parameters, three-dimensional (3D) computed
      tomographic (CT) rendering of the electroporation zone, and histopathology after
      CT-guided irreversible electroporation (IRE) in an acute porcine liver model as a
      potential strategy to improve IRE performance. METHODS: After Ethics Committee
      approval was obtained, in five landrace pigs, two IREs of the right and left
      liver (RL and LL) were performed under CT guidance with identical electroporation
      parameters. Before IRE, transarterial marking of the LL was performed with
      iodized oil. Nonenhanced and contrast-enhanced CT examinations followed. One hour
      after IRE, animals were killed and livers collected. Mean resulting voltage and
      amperage during IRE were assessed. For 3D CT rendering of the electroporation
      zone, parameters for size and shape were analyzed. Quantitative data were
      compared by the Mann-Whitney test. Histopathological differences were assessed.
      RESULTS: Mean resulting voltage and amperage were 2,545.3 +/- 66.0 V and 26.1 +/-
      1.8 A for RL, and 2,537.3 +/- 69.0 V and 27.7 +/- 1.8 A for LL without
      significant differences. Short axis, volume, and sphericity index were 16.5 +/-
      4.4 mm, 8.6 +/- 3.2 cm(3), and 1.7 +/- 0.3 for RL, and 18.2 +/- 3.4 mm, 9.8 +/-
      3.8 cm(3), and 1.7 +/- 0.3 for LL without significant differences. For RL and LL,
      the electroporation zone consisted of severely widened hepatic sinusoids
      containing erythrocytes and showed homogeneous apoptosis. For LL, iodized oil
      could be detected in the center and at the rim of the electroporation zone.
      CONCLUSION: There is no adverse effect of previous ITM on technical parameters,
      3D CT rendering of the electroporation zone, and histopathology after CT-guided
      IRE of the liver.

PMID- 24870701
TI  - Pediatric in vitro and in silico models of deposition via oral and nasal
      inhalation.
AB  - Respiratory tract deposition models provide a useful method for optimizing the
      design and administration of inhaled pharmaceutical aerosols, and can be useful
      for estimating exposure risks to inhaled particulate matter. As aerosol must
      first pass through the extrathoracic region prior to reaching the lungs,
      deposition in this region plays an important role in both cases. Compared to
      adults, much less extrathoracic deposition data are available with pediatric
      subjects. Recently, progress in magnetic resonance imaging and computed
      tomography scans to develop pediatric extrathoracic airway replicas has
      facilitated addressing this issue. Indeed, the use of realistic replicas for
      benchtop inhaler testing is now relatively common during the development and in
      vitro evaluation of pediatric respiratory drug delivery devices. Recently, in
      vitro empirical modeling studies using a moderate number of these realistic
      replicas have related airway geometry, particle size, fluid properties, and flow
      rate to extrathoracic deposition. Idealized geometries provide a standardized
      platform for inhaler testing and exposure risk assessment and have been designed
      to mimic average in vitro deposition in infants and children by replicating
      representative average geometrical dimensions. In silico mathematical models have
      used morphometric data and aerosol physics to illustrate the relative importance
      of different deposition mechanisms on respiratory tract deposition. Computational
      fluid dynamics simulations allow for the quantification of local deposition
      patterns and an in-depth examination of aerosol behavior in the respiratory
      tract. Recent studies have used both in vitro and in silico deposition
      measurements in realistic pediatric airway geometries to some success. This
      article reviews the current understanding of pediatric in vitro and in silico
      deposition modeling via oral and nasal inhalation.

PMID- 24870702
TI  - Aerosol deposition in the human lung in reduced gravity.
AB  - The deposition of aerosol in the human lung occurs mainly through a combination
      of inertial impaction, gravitational sedimentation, and diffusion. For 0.5- to 5
      MUm-diameter particles and resting breathing conditions, the primary mechanism of
      deposition in the intrathoracic airways is sedimentation, and therefore the fate
      of these particles is markedly affected by gravity. Studies of aerosol deposition
      in altered gravity have mostly been performed in humans during parabolic flights
      in both microgravity (MUG) and hypergravity (~1.6G), where both total deposition
      during continuous aerosol mouth breathing and regional deposition using aerosol
      bolus inhalations were performed with 0.5- to 3-MUm particles. Although total
      deposition increased with increasing gravity level, only peripheral deposition as
      measured by aerosol bolus inhalations was strongly dependent on gravity, with
      central deposition (lung depth<200 mL) being similar between gravity levels. More
      recently, the spatial distribution of coarse particles (mass median aerodynamic
      diameter~5 MUm) deposited in the human lung was assessed using planar gamma
      scintigraphy. The absence of gravity caused a smaller portion of 5-MUm particles
      to deposit in the lung periphery than in the central region, where deposition
      occurred mainly in the airways. Indeed, 5-MUm-diameter particles deposit either
      by inertial impaction, a mechanism most efficient in the large and medium-sized
      airways, or by gravitational sedimentation, which is most efficient in the distal
      lung. On the contrary, for fine particles (~1 MUm), both aerosol bolus
      inhalations and studies in small animals suggest that particles deposit more
      peripherally in MUG than in 1G, beyond the reach of the mucociliary clearance
      system.

PMID- 24870704
TI  - Birth of a healthy boy after PGD for X-linked heterotaxy syndrome.

PMID- 24870705
TI  - Forgotten fluids of the reproductive tract.

PMID- 24870706
TI  - Catalytic transparency of hexagonal boron nitride on copper for chemical vapor
      deposition growth of large-area and high-quality graphene.
AB  - Graphene transferred onto h-BN has recently become a focus of research because of
      its excellent compatibility with large-area device applications. The requirements
      of scalability and clean fabrication, however, have not yet been satisfactorily
      addressed. The successful synthesis of graphene/h-BN on a Cu foil and DFT
      calculations for this system are reported, which demonstrate that a thin h-BN
      film on Cu foil is an excellent template for the growth of large-area and high
      quality graphene. Such material can be grown on thin h-BN films that are less
      than 3 nm thick, as confirmed by optical microscopy and Raman spectroscopy. We
      have evaluated the catalytic growth mechanism and the limits on the CVD growth of
      high-quality and large-area graphene on h-BN film/Cu by performing Kelvin probe
      force microscopy and DFT calculations for various thicknesses of h-BN. 

PMID- 24870703
TI  - Birth defects and congenital health risks in children conceived through assisted
      reproduction technology (ART): a meeting report.
AB  - PURPOSE: Assisted Reproduction Treatment (ART) is here to stay. This review
      addresses the parental background of birth defects, before, during and after
      conception and focuses both on the underlying subfertility and on the question
      whether ART as a treatment is an additional contributing factor. METHODS:
      Searches were performed in Medline and other databases. Summaries were discussed
      in a Delphi panel set-up by the European Society of Human Reproduction and
      Embryology (ESHRE). RESULTS: Several birth defects and adult diseases arise
      during the earliest stages of ovarian development and oocyte differentiation:
      this is the case of cleft palate disorders in offspring from female rat exposed
      to Dioxin during fetal life or the polycystic ovary diseases in female offspring
      (primates) exposed to elevated androgen concentration during fetal life. Human
      oocytes and embryos often fail to stop the propagation of aneuploid cells but
      maintain their ability to repair DNA damages including those introduced by the
      fertilizing sperm. There is a 29 % increased risk of birth defects in the
      newborns spontaneously conceived by subfertile couples and the risk is further
      increased (34 %) when conception is achieved by treating infertlity with ART
      (Danish IVF Registry). Periconceptional conditions are critical for ART babies:
      their birth weight is in general smaller (Norvegian Registry) but a more
      prolonged culture time doubled the number of large babies (Finnish Registry).
      CONCLUSION: The long-term developmental effects of ART on child and subsequent
      health as an adult remains a subject worthy of futher monitoring and
      investigation.

PMID- 24870707
TI  - Safety first: the case against oral sodium phosphate.

PMID- 24870709
TI  - Reply to Yamashita et al.

PMID- 24870708
TI  - Major bleeding after endoscopic biopsy in relation to use of antithrombotics.

PMID- 24870710
TI  - Follow-up after colonic polypectomy in 2014: is there a French paradox?

PMID- 24870711
TI  - Reply to Heresbach & Pienkowski.

PMID- 24870712
TI  - Hennekam syndrome: a rare and often ignored cause of intestinal lymphangiectasia.

PMID- 24870715
TI  - Place of colorectal stents in therapeutic management of malignant large bowel
      obstructions.

PMID- 24870716
TI  - Show me the skin! Does seeing the back enhance tactile acuity at the back?
AB  - A growing body of literature associates musculoskeletal disorders with cortical
      reorganisation. One condition in which reorganisation is established and
      treatments that 'train the brain' are being widely used is chronic back pain.
      Recent evidence suggests that treatments that involve tactile training are more
      effective if they incorporate multisensory mechanisms, most obviously vision.
      With regard to back pain however, we must first determine if tactile function is
      enhanced by incorporating other modalities. A series of three cross-over
      experiments were conducted in healthy pain-free subjects to determine whether
      tactile acuity is enhanced when participants can see the skin of their back
      during testing. An initial randomised cross-over experiment suggested tactile
      acuity was significantly enhanced when participants could see their backs (t(25)
      = -4.226, p < 0.001, r = 0.65). However, a second replication experiment was not
      corroborative. Both the second (F(3,66) = 1.00, p = 0.398) and third (t(9) =
      0.969, p = 0.358) experiments suggested that seeing the back did not
      significantly affect tactile acuity, confirming that our initial results were
      likely due to chance. The principle that visual feedback improves tactile acuity
      at the hand does not apply to the back. These results strongly suggest that
      attempts to enhance tactile training by incorporating vision will not offer the
      benefit to treatment of back pain that has been observed for treatment of hand
      pain. 

PMID- 24870717
TI  - Effects of external pelvic compression on trunk and hip muscle EMG activity
      during prone hip extension in females with chronic low back pain.
AB  - Many studies have reported higher trunk and hip muscle activity in patients with
      chronic low back pain (CLBP). Increased trunk and hip muscle activity could
      contribute to pain. Previous studies have shown that external pelvic compression
      (EPC) decreased back and hip muscle activity during physical tasks. In this
      study, we assessed the effects of EPC on the electromyography (EMG) activity of
      the latissimus dorsi (LD), elector spinae (ES), gluteus maximus (GM), and biceps
      femoris (BF) in a CLBP group and a healthy group during prone hip extension
      (PHE). Forty female volunteers (20 non-specific CLBP, 20 healthy) were recruited.
      Surface EMG data were collected from the LD, ES, GM, and BF muscles during a PHE
      task. Normalized EMG values were analyzed by separate repeated-measures analysis
      of variance (ANOVA) for each muscle. The normalized EMG activity in the left LD,
      bilateral ES, and right GM was significantly higher in the CLBP group than in the
      healthy group during PHE. In the CLBP group, the normalized EMG activity in the
      left LD, bilateral ES, and right GM was significantly lower with EPC than without
      (p < 0.05). This suggests that the application of EPC decreased trunk and hip
      extensor EMG activity in the CLBP group during PHE. 

PMID- 24870718
TI  - Altering the activation mechanism in Thermomyces lanuginosus lipase.
AB  - It is shown by rational site-directed mutagenesis of the lid region in
      Thermomyces lanuginosus lipase that it is possible to generate lipase variants
      with attractive features, e.g., high lipase activity, fast activation at the
      lipid interface, ability to act on water-soluble substrates, and enhanced calcium
      independence. The rational design was based on the lid residue composition in
      Aspergillus niger ferulic acid esterase (FAEA). Five constructs included lipase
      variants containing the full FAEA lid, a FAEA-like lid, an intermediate lid of
      FAEA and TlL character, and the entire lid region from Aspergillus terreus lipase
      (AtL). To investigate an altered activation mechanism for each variant compared
      to that of TlL, a combination of activity- and spectroscopic-based measurements
      were applied. The engineered variant with a lid from AtL displayed interfacial
      activation comparable to that of TlL, whereas variants with FAEA lid character
      showed interfacial activation independence with pronounced activity toward pNP
      acetate and pNP-butyrate below the critical micelle concentration. For variants
      with lipase and esterase character, lipase activity measurements further
      indicated a faster activation at the lipid interface. Relative to their activity
      toward pNP-ester substrates in calcium-rich buffer, all lid variants retained
      between 15 and 100% activity in buffer containing 5 mM EDTA whereas TlL activity
      was reduced to less than 2%, demonstrating the lid's central role in governing
      calcium dependency. For FAEA-like lid variants, accessible hydrophobic surface
      area measurements showed an approximate 10-fold increase in the level of binding
      of extrinsic fluorophores to the protein surface relative to that of TlL
      accompanied by a blue shift in emission indicative of an open lid in aqueous
      solution. Together, these studies report on the successful alteration of the
      activation mechanism in TlL by rational design creating novel lipases with new,
      intriguing functionalities. 

PMID- 24870720
TI  - The promise of dried fruits in cancer chemoprevention.
AB  - Chemoprevention is an attempt to use nontoxic natural and synthetic substances or
      their mixtures to intervene the relatively early stages of carcinogenesis, before
      invasive characteristics are manifested. The consumption of fruits is well known
      to reduce the risk of human cancers. Although most fruits are available only on a
      seasonal basis, recent advances in food processing technologies have made it
      possible to extend the shelf life of fruits and fruit-products. Fruits can be
      preserved by applying different drying processes to reduce the moisture content.
      Different varieties of dried fruits are now sold in supermarkets, thereby making
      them readily accessible to consumers. Since oxidative stress and chronic
      inflammation play important roles in cancer development, dried fruits with
      antioxidative and anti-inflammatory properties hold promise for cancer
      chemoprevention. The antioxidant, anti-inflammatory and chemopreventive
      activities of dried fruits are largely attributed to their polyphenols and
      vitamins. Dried fruits contain adequate amounts of bioactive principles, such as
      anthocyanins, acetogenins, catechins, coumarins, phenolic acids, terpenes,
      xanthones, and others. Since numerous health beneficial phytochemicals in fruits
      are conserved even after processing, regular intake of dried fruits can help
      prevent cancer. This review addresses the chemopreventive potential of
      representative dried fruits and their active constituents. 

PMID- 24870719
TI  - ImmunoPET and biodistribution with human epidermal growth factor receptor 3
      targeting antibody 89Zr-RG7116.
AB  - The humanized monoclonal antibody with high affinity for the human epidermal
      growth factor receptor (HER) 3, RG7116, is a glycoengineered, IgG1 class
      antibody. By labeling RG7116 with zirconium-89 ((89)Zr) we aimed to visualize in
      vivo HER3 expression and study the biodistribution of this antibody in human
      tumor-bearing mice. Biodistribution of (89)Zr-RG7116 was studied in
      subcutaneously xenografted FaDu tumor cells (HER3-positive). Dose-dependency of
      (89)Zr-RG7116 organ distribution and specific tumor uptake was assessed by
      administering doses ranging from 0.05 to 10 mg/kg RG7116 to SCID/Beige mice.
      Biodistribution was analyzed at 24 and 144 h after injection. MicroPET imaging
      was performed at 1, 3, and 6 days after injection of 1.0 mg/kg (89)Zr-RG7116 in
      the FaDu, H441, QG-56 and Calu-1 xenografts with varying HER3 expression. The
      excised tumors were analyzed for HER3 expression. Biodistribution analyses showed
      a dose- and time-dependent (89)Zr-RG7116 tumor uptake in FaDu tumors. The highest
      tumor uptake of (89)Zr-RG7116 was observed in the 0.05 mg/kg dose group with
      27.5%ID/g at 144 h after tracer injection. MicroPET imaging revealed specific
      tumor uptake of (89)Zr-RG7116 in FaDu and H441 models with an increase in tumor
      uptake over time. Biodistribution data was consistent with the microPET findings
      in FaDu, H441, QG56 and Calu-1 xenografts, which correlated with HER3 expression
      levels. In conclusion, (89)Zr-RG7116 specifically accumulates in HER3 expressing
      tumors. PET imaging with this tracer provides real-time non-invasive information
      about RG7116 distribution, tumor targeting and tumor HER3 expression levels.

PMID- 24870721
TI  - Breast cancer: major risk factors and recent developments in treatment.
AB  - Breast cancer is the most common in women worldwide, with some 5-10% of all cases
      due to inherited mutations of BRCA1 and BRCA2 genes. Obesity, hormone therapy and
      use of alcohol are possible causes and over-expression of leptin in adipose
      tissue may also play a role. Normally surgery, radiation therapy and chemotherapy
      allow a good prognosis where screening measures are in place. New hope in
      treatment measures include adjuvant therapy, neoadjuvant therapy, and
      introduction of mono-clonal antibodies and enzyme inhibitors. 

PMID- 24870722
TI  - Ovarian cancer: interplay of vitamin D signaling and miRNA action.
AB  - Increasing attention is being devoted to the mechanisms by which cells receive
      signals and then translate these into decisions for growth, death, or migration.
      Recent findings have presented significant breakthroughs in developing a deeper
      understanding of the activation or repression of target genes and proteins in
      response to various stimuli and of how they are assembled during signal
      transduction in cancer cells. Detailed mechanistic insights have unveiled new
      maps of linear and integrated signal transduction cascades, but the multifaceted
      nature of the pathways remains unclear. Although new layers of information are
      being added regarding mechanisms underlying ovarian cancer and how polymorphisms
      in VDR gene influence its development, the findings of this research must be
      sequentially collected and re-interpreted. We divide this multi-component review
      into different segments: how vitamin D modulates molecular network in ovarian
      cancer cells, how ovarian cancer is controlled by tumor suppressors and oncogenic
      miRNAs and finally how vitamin D signaling regulates miRNA expression.
      Intra/inter-population variability is insufficiently studied and a better
      understanding of genetics of population will be helpful in getting a step closer
      to personalized medicine. 

PMID- 24870723
TI  - Induction of microRNA-9 mediates cytotoxicity of curcumin against SKOV3 ovarian
      cancer cells.
AB  - BACKGROUND: Curcumin, a phenolic compound extracted from the rhizomes of Curcuma
      longa, has shown cytotoxic effects against a variety of cancers. The aim of this
      study was to identify potential microRNA (miRNA) mediators of the anticancer
      effects of curcumin in ovarian cancer cells. MATERIALS AND METHODS: SKOV3 ovarian
      cancer cells were treated with curcumin (10-60 MUM) and miR-9 expression, cell
      proliferation, and apoptosis were assessed. The effects of miR-9 depletion on
      curcumin-mediated growth suppression were also examined. Phosphorylation of Akt
      and forkhead box protein O1 (FOXO1) was measured in cells with miR-9
      overexpression or curcumin treatment. RESULTS: Curcumin caused a significant and
      dose-dependent increase of miR-9 expression in SKOV3 cells, while significantly
      impeding cell proliferation and stimulating apoptosis. Depletion of miR-9
      significantly (p<0.05) attenuated the growth-suppressive effects of curcumin on
      SKOV3 cells, coupled with reduced percentages of apoptotic cells. In contrast,
      overexpression of miR-9 significantly enhanced the cleavage of caspase-3 and
      poly(ADP-ribose) polymerase and promoted apoptotic death in SKOV3 cells. Western
      blot analysis showed that both miR-9 overexpression and curcumin similarly caused
      a significant (p<0.05) decline in the phosphorylation of Akt and FOXO1, compared
      to untreated cells. CONCLUSIONS: The present study provided evidence that
      curcumin exerts its cytotoxic effects against SKOV3 ovarian cancer cells largely
      through upregulation of miR-9 and subsequent modulation of Akt/FOXO1 axis.
      Further studies are needed to identify direct targets of miR-9 that mediate the
      anticancer effects of curcumin in ovarian cancer cells.

PMID- 24870724
TI  - Prognostic significance of C-reactive protein in urological cancers: a systematic
      review and meta-analysis.
AB  - BACKGROUND: C-reactive protein (CRP), considered as a prototypical inflammatory
      cytokine, has been proposed to be involved in tumor progression through
      inflammation. Recent studies have indicated CRP as a progostic predictor for
      urological cancers, but the results remain controversial. MATERIALS AND METHODS:
      A systematic search of Medline, Scopus and the Cochrane Library was performed to
      identify eligible studies published between Jan 1, 2001 and Sep 1, 2013. Outcomes
      of interest were collected from studies comparing overall survival (OS), cancer
      specific survival (CSS) and relapse-free survival (RFS) in patients with elevated
      CRP levels and those having lower levels. Studies were pooled, and combined
      hazard ratio (HR) of CRP with its 95% confidence interval (CI) for survival were
      used for the effect size estimate. RESULTS: A total of 43 studies (7,490
      patients) were included in this meta-analysis (25 for RCC, 10 for UC, and 8 for
      PC). Our pooled results showed that elevated serum CRP level was associated with
      poor OS (HR: 1.26, 95%CI: 1.22-1.30) and RFS (HR: 1.38 95%CI: 1.29-1.47),
      respectively. For CSS the pooled HR (HR: 1.33, 95%CI: 1.28-1.39) for higher CRP
      expression could strongly predict poorer survival in urological cancers.
      Simultaneously, elevated serum CRP was also significantly associated with poor
      prognosis in the subgroup analysis. CONCLUSIONS: Our pooled results demonstrate
      that a high serum level of CRP as an inflammation biomarker denotes a poor
      prognosis of patients with urological cancers. Further large prospective studies
      should be performed to confirm whether CRP, as a biomarker of inflammation, has a
      prognostic role in urological cancer progression.

PMID- 24870725
TI  - Serum 25-hydroxy vitamin D status is not related to osteopenia/osteoporosis risk
      in colorectal cancer survivors.
AB  - BACKGROUND: The incidence of colorectal cancer increases with vitamin D
      deficiency as shown in recently published studies. In addition, prospective
      investigations have indicated that low vitamin D levels may be associated with
      increased mortality of colorectal cancer, especially in stage III and IV cases.
      However, the exact incidence of vitamin D deficiency and the relation between
      vitamin D deficiency and osteopenia/osteporosis is still not known. The aim of
      this study is to identify severity of vitamin D deficiency and absolute risk
      factors of osteopenia/osteoporosis in colorectal cancer survivors. MATERIALS AND
      METHODS: A total of 113 colorectal cancer survivors treated with surgery and/or
      chemotherapy +/- radiotherapy were recruited from medical oncology outpatient
      clinics during routine follow-up visits in 2012-2013. Bone mineral densitometry
      (BMD) was performed, and serum 25-OH vitamin D levels were also checked on the
      same day of the questionnaire. The patients was divided into 2 groups, group A
      with normal BMD and group B with osteopenia/osteoporosis. RESULTS: The median age
      of the study population was 58 (40-76). Thirty (30.0%) were female, whereas 79
      (70.0%) were male. The median follow-up was 48 months (14-120 months). Vitamin D
      deficiency was found in 109 (96.5%); mild deficiency (20-30 ng/ml) in 19 (16.8%),
      moderate deficiency (10-20 ng/ml) in 54 (47.8%) and severe deficiency (<10 ng/ml)
      in 36 (31.9%). Osteopenia was evident in 58 (51.4%) patients whereas osteoporosis
      was noted in 17 (15.0%) . Normal BMD was observed in 38 (33.6%). No apparent
      effects of type of surgery, presence of stoma, chemotherapy, radiotherapy and TNM
      stage were found regarding the risk of osteopenia and osteoporosis. Also, the
      severity of the vitamin D deficiency had no effect in the risk of osteopenia and
      osteporosis (p=0.93). In female patients, osteopenia/osteoporosis were observed
      in 79.5% patients as compared to 60.7% of male patients (p=0.04). CONCLUSIONS: In
      our study, vitamin D deficiency and osteopenia/osteoporosis was observed in 96.5%
      and 66.4% of colorectal cancer survivors, respectively. There is no defined
      absolute risk factor of osteopenia and osteoporosis in colorectal cancer
      survivors. To our knowledge, in the literature, our study is the first to
      evaluate all the risk factors of osteopenia and osteoporosis in colorectal cancer
      survivors.

PMID- 24870726
TI  - Economic evaluation of prostate cancer screening test as a national cancer
      screening program in South Korea.
AB  - BACKGROUND: Prostate cancer is rapidly increasing in Korea and professional
      societies have requested adding prostate specific antigen (PSA) testing to the
      National Cancer Screening Program (NCSP), but this started a controversy in Korea
      and neutral evidence on this issue is required more than ever. The purpose of
      this study was to provide economic evidence to the decision makers of the NCSP.
      MATERIALS AND METHODS: A cost-utility analysis was performed on the adoption of
      PSA screening program among men aged 50-74-years in Korea from the healthcare
      system perspective. Several data sources were used for the cost-utility analysis,
      including general health screening data, the Korea Central Cancer Registry,
      national insurance claims data, and cause of mortality from the National
      Statistical Office. To solicit the utility index of prostate cancer, a face-to
      face interview for typical men aged 40 to 69 was conducted using a Time-Trade Off
      method. RESULTS: As a result, the increase of effectiveness was estimated to be
      very low, when adopting PSA screening, and the incremental cost effectiveness
      ratio (ICER) was analyzed as about 94 million KRW. Sensitivity analyses were
      performed on the incidence rate, screening rate, cancer stage distribution,
      utility index, and treatment costs but the results were consistent with the base
      analysis. CONCLUSIONS: Under Korean circumstances with a relatively low incidence
      rate of prostate cancer, PSA screening is not cost-effective. Therefore, we
      conclude that adopting national prostate cancer screening would not be beneficial
      until further evidence is provided in the future.

PMID- 24870727
TI  - Role of vitamin D deficiency and lack of sun exposure in the incidence of
      premenopausal breast cancer: a case control study in Sabzevar, Iran.
AB  - BACKGROUND: Vitamin D has been suggested as one of the critical factors for
      female reproductive health with protective activities against different cancers
      but there are conflicting facts regarding its role on breast cancer without any
      clear data on premenopausal cases. This study aimed to evaluate the role of
      vitamin D from dietary sources and sunlight exposure on the incidence of
      premenopausal breast cancer. MATERIALS AND METHODS: We conducted a case control
      study on 60 newly diagnosed premenopausal breast cancer patients and 116 normal
      women who lived in Sabzevar and surrounding villages in Razavi, Khorasan, a rural
      and conservative area of Iran. RESULTS: The mean concentrations of 25-OH vitamin
      D in cases and controls were 15.2 +/- 8.15 vs 15.5 +/- 7/45 ng/ml, both well
      below normal values elsewhere. In fact 50% of analyzed individuals showed very
      severe or severe vitamin D deficiency and the rest (25%) were detected in
      suboptimal levels. Although the lack of vitamin D and calcium supplementation
      increased slightly the risk of premenopausal breast cancer (p=0.009, OR=1.115, CI
      95%=1.049-1.187), higher prevalence of weekly egg consumption (86.66% vs 96.55%,
      p=0.023, OR=0.232, CI 95% 0.065-0.806) showed a slight protective role. The last
      but the most important risk factor was lack of sunlight exposure because the
      breast cancer patients had total body coverage from sun (p=0.007, OR=10.131, CI
      98% 0.314-78.102). CONCLUSION: This study pointed out the role of vitamin D and
      other possible risk factors on the development and growth of breast tumors in
      this special geographical region. Although this study has revealed the
      interactions between hormonal and environmental factors in this province of Iran,
      understanding the deficiency pattern and its contribution to other lifestyle
      factors elsewhere is also necessary.

PMID- 24870728
TI  - A new cell counting method to evaluate anti-tumor compound activity.
AB  - Determining cell quantity is a common problem in cytology research and anti-tumor
      drug development. A simple and low-cost method was developed to determine
      monolayer and adherent-growth cell quantities. The cell nucleus is located in the
      cytoplasm, and is independent. Thus, the nucleus cannot make contact even if the
      cell density is heavy. This phenomenon is the foundation of accurate cell-nucleus
      recognition. The cell nucleus is easily recognizable in images after fluorescent
      staining because it is independent. A one-to-one relationship exists between the
      nucleus and the cell; therefore, this method can be used to determine the
      quantity of proliferating cells. Results indicated that the activity of the
      histone deacetylase inhibitor Z1 was effective after this method was used. The
      nude-mouse xenograft model also revealed the potent anti-tumor activity of Z1.
      This research presents a new anti-tumor-drug evaluation method. 

PMID- 24870729
TI  - Risk of breast cancer and total malignancies in rheumatoid arthritis patients
      undergoing TNF-alpha antagonist therapy: a meta-analysis of randomized control
      trials.
AB  - CONTEXT: Interest exits in whether TNF-alpha antagonists increase the risk of
      breast cancer and total malignancies in patients with rheumatoid arthritis (RA).
      OBJECTIVES: To analyze the risk of malignancies, especially breast cancer, in
      patients with RA enrolled in randomized control trials (RCTs). METHODS: A
      systematic literature search for RCTs from 1 January 1998 to 1 July 2013 from
      online databases, such as PubMed, WILEY, EMBASE, ISI web of knowledge and
      Cochrane Library was conducted. Studies included RCTs that compared the safety of
      at least one dose of the five TNF-alpha antagonists with placebo or methotrexate
      (MTX) (or TNF-alpha antagonists plus MTX vs placebo plus MTX) in RA patients for
      more than 24 weeks and imported all the references into document management
      software EndNotex6. Two independent reviewers selected studies and extracted the
      data about study design, patients' characteristics and the type, number of all
      malignancies. RESULTS: 28 RCTs from 34 records with 11,741 patients were
      analyzed. Of the total, 97 developed at least one malignancy during the double
      blind trials, and breast cancer was observed in 17 patients (17.5% of total
      malignancies). However, there was no statistically significant increased risk
      observed in either the per protocol (PP) model (OR 0.65, 95%CI [0.22, 1.93]) or
      the modified intention to treat (mITT) model (OR 0.75, 95%CI [0.25, 2.21]). There
      were also no significant trend for increased risk of total malignancies on anti
      TNF-alpha therapy administered at approved doses in either model (OR, 1.06, 95%CI
      [0.64, 1.75], and OR, 1.30, 95%CI [0.80, 2.14], respectively). As to the two
      models, modified intention to treat model analysis led to higher estimation than
      per protocol model analysis. CONCLUSIONS: This study did not find a significantly
      increased risk of breast cancer and total malignancies in adults RA patients
      treated with TNF-alpha antagonists at approved doses. However, it cannot be
      ignored that more patients developed malignancies with TNF-alpha antagonists
      therapy compared with patients with placebo or MTX, in spite of the lack of
      statistical significance, so that more strict clinical trials and long-term
      follow-up are needed, and both mITT and PP analyses should be used in such safety
      analyses.

PMID- 24870730
TI  - Cytomorphologic patterns of breast lesions in Sudanese patients: lessons learned
      from fine needle aspiration cytology.
AB  - BACKGROUND: Cytology for breast lesions is a safe, rapid and cost-effective with
      a high specificity and sensitivity. OBJECTIVE: To determine the cytomorphologic
      patterns of breast lesions identified among a group of Sudanese patients.
      MATERIALS AND METHODS: This study included 759 patients undergoing either a fine
      needle aspiration FNA, nipple discharge (ND) smears or breast skin scraping (SS)
      at a cytology clinic in Khartoum. Clinical and demographic data were reviewed.
      Stained smears were categorized into: inadequate sample, normal breast, benign
      lesion, suspicious, or malignant neoplasm. RESULTS: of the 759 cases, 734
      (96.71%) were FNA, 18 (2.37%) ND and 7 cases (0.92%) SS. For 28 cases, FNA was
      done under ultrasound guidance. Females were 720 (94.86%). Benign lesions were
      423(55.75%) and 248 (32.67%) were malignant and 77 (10.14%) of smears were normal
      without any detected abnormality. Ten (1.31%) cases were suspicious for
      malignancy, and only one case (0.13%) was reported as inadequate. Most lesions
      were observed among the age group 30 years and above. CONCLUSION: Most patients
      investigated have benign lesions, one third of cytological smears were malignant.
      FNAC is a useful tool for investigating breast lesions in limited-resource
      settings.

PMID- 24870731
TI  - Lack of relation of AKAP12 with p53 and Bcl-2 in colorectal carcinoma.
AB  - BACKGROUND: AKAP12 inhibits oncogenic proliferation, invasion, chemotaxis and
      neovascularization. Bcl-2 and p53 are two important apoptotic markers that play
      roles in apoptotic processes. It has been found that AKAP12 blocks the cell cycle
      and induces apoptosis in fibrosarcoma cells. In our study we assessed the
      relationship of AKAP12 with apoptotic markers, Bcl-2 and p53. MATERIALS AND
      METHODS: Our study included 45 cases that were histopathologically diagnosed with
      colorectal carcinoma from the tissue samples acquired by surgical resection. AKAP
      12, Bcl-2, and p53 expression was examined by immunohistochemistry. RESULTS: A
      total of 45 colorectal adenocarcinoma patients - 17 (37.8%) females and 28
      (62.2%) males - were included in this study. AKAP12 expression was found to be
      negative in 8 patients (17.8%), and positive in 37 patients (82.2%). Bcl-2 was
      found positive in 6 patients (13.3%) and p53 in 29 patients (55.6%). AKAP12
      expression had no significant relation with Bcl-2 and p53 expression (p:0.939,
      p:0.079, respectively). CONCLUSIONS: Although various studies have pointed to
      apoptotic activity of AKAP12, the literature is limited regarding relations with
      p53 or Bcl-2 expression. In the present study, we found no relation in colorectal
      carcinomas.

PMID- 24870732
TI  - Effectiveness and safety of pemetrexed versus docetaxel as a treatment for
      advanced non-small cell lung cancer: a systematic review and meta-analysis.
AB  - BACKGROUND: Our aim was to conduct a meta-analysis to compare the efficacy and
      safety of pemetrexed and docetaxel for non-small cell lung cancer (NSCLC).
      MATERIALS AND METHODS: We systematically searched the Cochrane Library, PubMed,
      Embase, China Biology Medicine Database for randomized controlled trials (RCTs)
      comparing the efficacy and toxicities of pemetrexed versus docetaxel as a
      treatment for advanced NSCLC. We limited the languages to English and Chinese.
      Two reviewers independently screened articles to identify eligible trials
      according to the inclusion and exclusion criteria and assessed the methodological
      quality of included trials, and then extracted data. The meta-analysis was
      performed using STATA12.0. RESULTS: Six RCTs involving 1,414 patients were
      identified. We found that there was no statistically significant differences in
      overall response rate, survival time, progression-free survival, disease control
      rate, and 1-2 yr survival rate (p>0.050) but it is worthy of mention that
      patients in the pemetrexed arms had significantly higher 3-yr survival rate
      (P=0.002). With regard to the grade 3 or 4 hematological toxicity, compared with
      docetaxel, pemetrexed led to lower rate of grade 3-4 febrile neutropenia,
      neutropenia, and leukocyts toxicity (p<0.001). There was no significant
      difference in anemia between the two arms (p=0.08). In addition, pemetrexed led
      to higher rate of grade 3-4 thrombocytopenia toxicity (p=0.03). As for the non
      hematological toxicities, compared with docetaxel, pemetrexed group had lower
      rate of grade 3-4 diarrhea and alopecia. CONCLUSIONS: Pemetrexed was almost as
      effective as docetaxel in patients with advanced NSCLC. At the same time,
      pemetrexed might increase the 3-yr survival rate. As for safety, pemetrexed led
      to lower rate of grade 3-4 febrile neutropenia, neutropenia, leukocytes, diarrhea
      and alopecia toxicity. However, it was associated with a higher rate of grade 3-4
      thrombocytopenia.

PMID- 24870733
TI  - Application of computed tomography for differential diagnosis of glioma stoke and
      simple cerebral hemorrhage.
AB  - OBJECTIVE: To explore the value of computed tomography (CT) in the differential
      diagnosis of glioma stroke and simple cerebral hemorrhage. MATERIALS AND METHODS:
      A total of 45 patients with glioma stroke and stroke as the initial symptom in
      our hospital from Jun., 2009 to Oct., 2013 were selected along with 50
      individuals with simple cerebral hemorrhage in the same period randomly collected
      as a control group. The CT results in both groups were analyzed and compared.
      RESULTS: In the observation group, there were 25 patients with astrocytoma
      (55.6%), 11 with oligodendroglioma (24.4%), 8 with ependymoma (17.2%) and 1 with
      glioblastoma multiforma (GBM, 2.22%). Additionally, the major CT manifestation
      was coexistence of hemorrhage and tumor signs. By comparison, it could be found
      that the proportions of patients respectively with peripheral edema and space-
      occupying effect in the observation group were significantly higher than in the
      control group (P<0.01). CONCLUSIONS: Application of CT examination combined with
      medical history in patients has very important clinical value in the differential
      diagnosis of glioma stroke and simple cerebral hemorrhage.

PMID- 24870734
TI  - Effect of perceived social support on psychosocial adjustment of Turkish patients
      with breast cancer.
AB  - AIMS: To identify the psychosocial adjustment of Turkish patients with breast
      cancer and the effects of perceived social support on their adjustment. MATERIALS
      AND METHODS: The sample comprised 100 volunteering patients diagnosed with breast
      cancer in the last six months reporting to the Outpatient Chemotherapy Unit at
      the Medical Faculty Hospital in northern Turkey. The data for the study were
      collected through the Descriptive Information Form, the Psychosocial Adjustment
      to Illness Scale-Self-reflection (PAIS-SR) and the Cancer-Specific Social Support
      Scale and analyzed via SPSS 16.0 for Windows. Descriptive statistics, Chi square
      test, ANOVA and correlation were used to evaluate data. RESULTS: There was a
      negative significant correlation between mean scores in the sub-scales of the
      social support scale and the ones in the sub-scales of the psychosocial
      adjustment to illness scale (p<0.05). Similarly, there was a negative significant
      correlation between confidence support and health care orientation as well as
      adjustment to social environment. Likewise, emotional support was in a negative
      significant correlation with health care orientation, adjustment to domestic
      environment, extended family relationships and adjustment to social environment.
      CONCLUSIONS: It was concluded that social support for patients with breast cancer
      had an influence on their psychosocial adjustment to illness. Holistic care
      should be given to breast cancer patients by oncology nurses especially in the
      first six months of treatment. It could be concluded that patients should be
      accompanied by their family/relatives in treatment and care following their
      diagnosis with breast cancer, that their family should be made more aware of the
      fact that the patient should be physically and psychologically supported, that
      patients with breast cancer should be provided with domiciliary care, and that
      they should be encouraged to participate in social support groups.

PMID- 24870735
TI  - Long-term survival of women with locally advanced breast cancer with >= 10
      involved lymph nodes at diagnosis.
AB  - BACKGROUND: Axillary lymph node status at diagnosis remains the strongest
      predictor of long-term survival in breast cancer. Patients with more than ten
      axillary lymph nodes at diagnosis have a poor long-term survival. In this single
      institutional study, we set out to evaluate the prognosis of this high-risk group
      in the era of multimodality therapy. MATERIALS AND METHODS: In this retrospective
      study, we looked at all breast cancer patients with greater than ten axillary
      lymph nodes diagnosed at Mount Sinai Medical Center (MSMC) from January 1st 1990
      to December 31st 2007 (n=161). In the univariate analysis, descriptive
      frequencies, median survival, and 5- and 10-year survival rates were estimated
      for common prognostic factors. A multivariate prognostic analysis for time-to
      event data, using the extended Cox regression model was carried out. RESULTS:
      With a median and mean follow-up of 70 and 89.9 months, respectively, the overall
      median survival was estimated to be 99 months. The five-year disease-free
      survival (DFS) was 59.3% and the ten-year DFS was 37.9%, whereas the five- and
      ten-year overall survival (OS) was 66.6% and 43.9%, respectively. Multivariate
      analysis revealed a significant improvement in DFS among black patients compared
      to whites (p=0.05), improved DFS and OS among young patients (ages 21-45)
      compared to elderly patients (age greater than 70) (p=0.00176, p=0.0034,
      respectively), and improved DFS and OS among patients whose tumors were ER
      positive (p=0.049, p=0.0034). CONCLUSIONS: In this single institution study of
      patients with greater than 10 positive axillary nodes, black patients had a
      significantly improved DFS compared with white patients. Young age and ER tumor
      positivity was associated with improved outcomes. Using multivariate analysis,
      there were no other variables associated with statistically significant
      improvements in DFS or OS including date of diagnosis. Further work is needed to
      improve breast cancer survival in this subgroup of patients.

PMID- 24870736
TI  - Predictive factors for neutropenia after docetaxel-based systemic chemotherapy in
      Korean patients with castration- resistant prostate cancer.
AB  - The aim of this study was to determine predictive factors for neutropenia after
      docetaxel-based systemic chemotherapy in patients with castration-resistant
      prostate cancer (CRPC). The study included 40 Korean CRPC patients who were
      treated with several cycles of docetaxel plus prednisolone from May 2005 to May
      2012. Patients were evaluated for neutropenia risk factors and for the incidence
      of neutropenia. In this study, nine out of forty patients (22.5%) developed
      neutropenia during the first cycle of docetaxel-based systemic chemotherapy. Four
      experienced grade 2, three grade 3, and one grade 4 neutropenia. Multivariate
      analysis showed that pretreatment white blood cell (WBC) count (p=0.042),
      pretreatment neutrophil count (p=0.015), pretreatment serum creatinine level
      (p=0.027), and pretreatment serum albumin level (p=0.017) were significant
      predictive factors for neutropenia. In conclusion, pretreatment WBC counts,
      neutrophil counts, serum creatinine levels, and serum albumin levels proved to be
      significant independent risk factors for the development of neutropenia induced
      by docetaxel-based systemic chemotherapy in patients with CRPC. 

PMID- 24870737
TI  - Clinical efficacy of bevacizumab concomitant with pemetrexed in patients with
      advanced non-small cell lung cancer.
AB  - OBJECTIVE: To observe the clinical efficacy of bevacizumab concomitant with
      pemetrexed in patients with advanced non-small cell lung cancer (NSCLC).
      MATERIALS AND METHODS: A total of 72 patients were randomly divided into a
      combination group (pemetrexed+bevacizumab, n=36) and a pemetrexed group (n=36)
      and assessed for disease control (CR+PR+SD) after 4-cycles of first-line GP
      chemotherapy (gemcitabine+cisplatin). Clinical efficacy, progression-free
      survival time (PFS), overall survival time (OS), overall response rate (ORR),
      disease control rate (DCR) and rate of adverse responses between two groups were
      observed and compared. RESULTS: ORR and DCR were 27.8% and 83.4% in combination
      group, and 16.7% and 69.5% in the pemetrexed group, respectively, but there were
      no significant differences (P>0.05). PFS in combination group and pemetrexed
      group were 4.6 months and 3.9 months respectively (P=0.09), whereas OS in the
      combination group was 14 months, evidently higher than in the pemetrexed group
      (11 months, P=0.004). Adverse responses in both groups included high blood
      pressure, bleeding, thrombocytopenia, anemia, elevated transaminase, diarrhea,
      vomiting and proteinuria, but there were no significant differences (P>0.05).
      CONCLUSIONS: Bevacizumab concomitant with pemetrexed has better clinical efficacy
      and safety, giving rise to prolonged survival time in patients with advanced
      NSCLC.

PMID- 24870738
TI  - Analysis of CEA expression and EGFR mutation status in non-small cell lung
      cancers.
AB  - BACKGROUND: The serum carcinoembryonic antigen (CEA) level can reflect tumor
      growth, recurrence and metastasis. It has been reported that epidermal growth
      factor receptor (EGFR) mutations in exons 19 and 21 may have an important
      relationship with tumor cell sensitivity to EGFR -TKI therapy. In this study, we
      investigated the clinical value of EGFR mutations and serum CEA in patients with
      non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: The presence of
      mutations in EGFR exons 19 and 21 in the tissue samples of 315 patients with
      NSCLC was detected with real-time fluorescent PCR technology, while the serum CEA
      level in cases who had not yet undergone surgery, radiotherapy, chemotherapy and
      targeted therapy were assessed by electrochemical luminescence. RESULTS: The
      mutation rates in EGFR exons 19 and 21 were 23.2% and 14.9%, respectively, with
      the two combined in 3.81%. Measured prior to the start of surgery, radiotherapy,
      chemotherapy and targeted treatment, serum CEA levels were abnormally high in
      54.3% of the patients. In those with a serum CEA level <5 ng/mL, the EGFR
      mutation rate was 18.8%, while with 5~19 ng/mL and >= 20 ng/mL, the rates were
      36.4% and 62.5%. In addition, in the cohort of patients with the CEA level being
      20~49 ng/mL, the EGFR mutation rate was 85.7%, while in those with the CEA level
      >= 50 ng/mL, the EGFR mutation rate was only 20.0%, approximately the same as in
      cases with the CEA level<5 ng/mL. CONCLUSIONS: There is a positive correlation
      between serum CEA expression level and EGFR mutation status in NSCLC patients,
      namely the EGFR mutation-positive rate increases as the serum CEA expression
      level rises within a certain range (>= 20 ng/mL, especially 20~49 ng/mL). If
      patient samples are not suitable for EGFR mutation testing, or cannot be obtained
      at all, testing serum CEA levels might be a simple and easy screening method.
      Hence, for the NSCLC patients with high serum CEA level (>= 20 ng/mL, especially
      20~49 ng/mL), it is worthy of attempting EGFR-TKI treatment, which may achieve
      better clinical efficacy and quality of life.

PMID- 24870739
TI  - Molecular markers for patients with thymic malignancies: not feasible at present?
AB  - BACKGROUND: Thymomas and thymic carcinomas are rare malignancies and devising
      clinically effective molecular targeted therapies is a major clinical challenge.
      The aim of the study was to analyze BLC2 and vascular endothelial growth factor
      receptor (VEGFR) expression and KRAS and EGFR mutational status and to correlate
      them with the clinical characteristics of patients with thymomas and thymic
      carcinomas. MATERIALS AND METHODS: A total of 62 patients (mean age: 50.4 +/-
      13.2 years) with thymomas and thymic carcinomas were enrolled. The expression of
      BLC2 and VEGFR in tumor cells and normal tissues was evaluated by RT-PCR. The
      mutational status of the KRAS and EGFR genes was investigated by PCR with
      sequence specific primers. RESULTS: The BLC2 and VEGFR expression levels did not
      differ significantly between tumor and normal tissues. Moreover, there were no
      clearly pathogenic mutations in KRAS or EGFR genes in any tumor. None of the
      molecular markers were significantly related to clinical outcomes. CONCLUSIONS:
      Changes in levels of expression of BLC2 and VEGFR do not appear to be involved in
      thymic tumorigenesis. Moreover, our data suggest that KRAS and EGFR mutations do
      not play a major role in the pathogenesis of thymomas and thymic carcinomas.

PMID- 24870740
TI  - Diagnostic value of endocervical curettage for detecting dysplastic lesions in
      women with atypical squamous cells of undetermined significance (ASC-US) and low
      grade squamous intraepithelial lesion (LSIL) Papanicolaou smears.
AB  - BACKGROUND: To determine the frequency of dysplastic lesions in the endocervical
      curettage (ECC) specimens of women with ASC-US and LSIL Pap and to evaluate the
      possible factors associated with high grade dysplasia in those ECC specimens.
      MATERIALS AND METHODS: Two hundred and sixty patients with ASC-US and LSIL
      cytologic smears who underwent an ECC at the time of colposcopic examination
      during January 2010 and December 2012 were reviewed. Demographic and
      clinicopathologic data were collected. Multivariate analysis using binary
      logistic regression was used to identify factors that might be associated with
      high grade endocervical dysplasia. RESULTS: The frequency of endocervical
      dysplasia was 7.7% (20 out of 260 patients). Cervical intraepithelial neoplasia
      (CIN) 1 and CIN 2-3 lesions in the endocervical canal were observed in 12 and 8
      patients, respectively. No microinvasive or invasive cervical cancers were
      identified. There was no difference in the frequency of high grade endocervical
      dysplasia between the patients with satisfactory and unsatisfactory colposcopic
      examinations (1.4% vs 5.1%, respectively, p=0.087). A multivariate logistic
      regression analysis demonstrated a significant association between high grade CIN
      on ectocervical biopsy as well as LSIL cytologic smears and high grade dysplasia
      in endocervical canal (OR=0.046, 95%CI=0.007-0.288; p=0.001 and OR=0.154,
      95%CI=0.025-0.942; p=0.043, respectively). CONCLUSIONS: The frequency of high
      grade endocervical dysplasia in women with ASC-US and LSIL cytologic smears was
      low. Therefore, routine performance of ECC in those women is debatable. High
      grade ectocervical dysplasia and LSIL cytologic smears may be used as predictors
      for high grade dysplasia in endocervical canal and ECC in these patients is
      reasonable.

PMID- 24870741
TI  - Family history and survival of patients with gastric cancer: a meta-analysis.
AB  - BACKGROUND: Previous studies have generated conflicting evidence regarding
      associations between family history and survival after gastric cancer surgery. In
      this study, we investigated this question using a meta-analysis. MATERIALS AND
      METHODS: To identify relevant studies, PubMed and Embase databases were searched
      up to June 2013. Two reviewers independently assessed search results and data
      extraction of included studies. Hazard ratios (HRs) and 95% confidence intervals
      (CIs) for overall survival (OS) were calculated based on fixed- or random-
      effects models. Homogeneity of effects across studies was assessed using x2 test
      statistics and quantified by I2. RESULTS: A total of five studies were selected
      according to the inclusion criteria. The total number of patients included was
      2,030, which ranged from 145 to 598 per study. There was no significant
      difference in OS by family history of cancer (HR=0.83, 95%CIs=0.50-1.38), but
      subgroup analysis of patients with a first-degree family history of cancer
      (HR=0.74, 95%CIs=0.60-0.93) and gastric cancer family history (HR=0.56,
      95%CIs=0.41-0.76) tended to show better OS in these patients. CONCLUSIONS: This
      meta-analysis suggests that a first-degree family history of cancer or gastric
      cancer family history is associated with better survival of gastric cancer
      patients after surgery, after a systematic review of five previous studies. These
      results can be applied by clinicians when counselling patients regarding their
      risk of death from gastric cancer. Further study is needed to investigate the
      underlying mechanism between family history and survival in gastric cancer
      patients.

PMID- 24870743
TI  - Inflammatory bowel disease and risk of cholangiocarcinoma: evidence from a meta
      analysis of population-based studies.
AB  - OBJECTIVE: Patients with inflammatory bowel disease (IBD) have an increased risk
      of extra-intestinal cancer, whereas its impact on cholangiocarcinoma (CC) remains
      unknown. The aim of this study was to obtain a reliable estimate of the risk of
      CC in IBD patients through a meta-analysis of clinical observational studies.
      METHODS: Relevant studies were retrieved by searching PUBMED, EMBASE and Web of
      Science Databases up to Dec 2013. Four population-based case-control and two
      cohort studies with IBD were identified. Summary relative risk (RR) and its
      corresponding 95% confidence interval (CI) were calculated using a random-effects
      model. Potential sources of heterogeneity were detected using subgroup analyses.
      RESULTS: The pooled risk estimate indicated IBD patients were at increased risk
      of CC (RR = 2.63, 95%CI = 1.47-4.72). Moreover, the increased risk of CC was also
      associated with Crohn's disease (RR = 2.69, 95%CI = 1.59-4.55) and ulcerative
      colitis (RR = 3.40, 95%CI = 2.50-4.62). In addition, site-specific analyses
      revealed that IBD patients had an increased risk of intrahepatic CC (ICC) (RR =
      2.61, 95%CI = 1.72-3.95) and extrahepatic CC (ECC) (RR = 1.47, 95%CI = 1.10-
      1.97). CONCLUSIONS: This study suggests the risk of CC is significantly increased
      among IBD patients, especially in ICC cases. Further studies are warranted to
      enable definite conclusions to be drawn.

PMID- 24870742
TI  - Exosome-derived microRNA-29c induces apoptosis of BIU-87 cells by down regulating
      BCL-2 and MCL-1.
AB  - BACKGROUND: Aberrant expression of the microRNA-29 family is associated with
      tumorigenesis and cancer progression. As transport carriers, tumor-derived
      exosomes are released into the extracellular space and regulate multiple
      functions of target cells. Thus, we assessed the possibility that exosomes could
      transport microRNA- 29c as a carrier and correlations between microRNA-29c and
      apoptosis of bladder cancer cells. MATERIALS AND METHODS: A total of 28 cancer
      and adjacent tissues were examined by immunohistochemistry to detect BCL-2 and
      MCL-1 expression. Disease was Ta-T1 in 12 patients, T2-T4 in 16, grade 1 in 8, 2
      in 8 and 3 in 12. The expression of microRNA-29c in cancer tissues was detected
      by quantitative reverse transcriptase PCR (QRT- PCR). An adenovirus containing
      microRNA-29c was used to infect the BIU-87 human bladder cancer cell line.
      MicroRNA-29c in exosomes was measured by QRT-PCR. After BIU-87 cells were induced
      by exosomes-derived microRNA-29c, QRT-PCR was used to detect the level of
      microRNA-29c. Apoptosis was examined by flow cytometry and BCL-2 and MCL-1 mRNA
      expressions were assessed by reverse transcription-polymerase chain reaction.
      Western blotting was used to determine the protein expression of BCL-2 and MCL-1.
      RESULTS: The expressions of BCL-2 and MCL-1 protein were remarkably increased in
      bladder carcinoma (p<0.05), but was found mainly in the basal and suprabasal
      layers in adjacent tissues. The expression of microRNA-29c in cancer tissues was
      negatively correlated with the BCL-2 and MCL-1. The expression level of microRNA
      29c in exosomes and BIU-87 cells from the experiment group was higher than that
      in control groups (p<0.05). Exosome-derived microRNA-29c induced apoptosis
      (p<0.01). Although only BCL-2 was reduced at the mRNA level, both BCL-2 and MCL-1
      were reduced at the protein level. CONCLUSIONS: Human bladder cancer cells
      infected by microRNA- 29c adenovirus can transport microRNA-29c via exosomes.
      Moreover, exosome-derived microRNA29c induces apoptosis in bladder cancer cells
      by down-regulating BCL-2 and MCL-1.

PMID- 24870744
TI  - See-and-treat approach to cervical intraepithelial lesions in HRH Princess Maha
      Chakri Sirindhorn Medical Center.
AB  - BACKGROUND: To evaluate the overtreatment rate with the see and treat approach in
      the management of women with abnormal cervical cytology. MATERIALS AND METHODS: A
      retrospective review of patients with abnormal cervical cytology who underwent S
      and T at MSMC between January 2008 and December 2012 was conducted. Loop
      electrosurgical excision procedure (LEEP), histological results, cytology and
      colposcopic impression were analyzed to evaluate overtreatment rate, cyto
      histologic correlation and related factors. RESULTS: Average age of S and T cases
      was 42 years. Ninety seven percents were referred from affiliated health care
      providers. The study revealed 83.2% patients had HSIL or higher from cervical
      cytology. Correlation between HSIL and final histology was relatively low at 75%
      compared to other studies. Overtreatment rate was 28%. CONCLUSIONS: S and T was
      done in 197 patients in a tertiary care health facility with patient
      satisfaction. Overtreatment occurred, but the rate can be reduced with
      appropriate recommendations. HSIL Pap smears should be reexamined before S and T
      while low grade and lesser colposcopic impression groups should obtain
      conventional colposcopic approach for patient future reproductive benefit.

PMID- 24870745
TI  - Symptom frequency of children with cancer and parent quality of life in Turkey.
AB  - BACKGROUND: This research was planned with the aim of determining the effect of
      symptom frequency of children with cancer on the quality of life of their
      parents. MATERIALS AND METHODS: In gathering the research data, the Child and
      Parent Information Form, the Symptom Evaluation Form and the Family Version of
      Life Quality Scale in Cancer Patients were used. Evaluation was made by using
      percentage calculations, Kruskal Wallis test, Bonferroni adjusted t-test and
      Bonferroni adjusted Mann-Whitney U test. The significance level was accepted as
      0.005. RESULTS: Some 37.6% of the participant children were female and 62.4% were
      male, with an average age of 10.2 +/- 4.5. While 41.0% were newly diagnosed,
      46.2% were in remission and 12.8% was in relapse. Highly significant differences
      were detected according to the symptom frequency with parent physical and
      psychological health, social anxiety, and spiritual wellness sub-dimensions, as
      well as total point averages. CONCLUSIONS: It is thought that following up the
      symptoms that might develop depending on cancer diagnosis and treatment and
      implementing nursing initiatives aimed at reducing the symptoms, knowing the
      importance of life quality, maintaining measures aimed at life quality and
      planning initiatives to increase the life quality will play a key role in
      maintaining and developing the health of Turkish paediatric oncology patients and
      their parents.

PMID- 24870747
TI  - Correlations between serum IL33 and tumor development: a meta-analysis.
AB  - BACKGROUND: Interleukin-33 (IL-33) has recently been implicated in tumor
      development. METHODS: Data was obtained from PubMed, EMBASE, Clinical trial,
      Cochrane Library, Web of Science, CNKI and Wanfang databases. After quality
      assessment and data extraction, a meta-analysis was performed using Review
      Manager 5. 2 software. RESULTS: There were eight documents included in this meta
      analysis. The results showed IL33 levels to be higher in tumor patients than that
      in health people, but no correlations tumor stage, metastasis and survival time
      of tumor patients were evident. CONCLUSION: IL33 may be useful as an alarm factor
      in tumor detection and prognosis.

PMID- 24870746
TI  - MAGED4 expression in glioma and upregulation in glioma cell lines with 5-aza-2'
      deoxycytidine treatment.
AB  - Melanoma-associated antigen (MAGE) family genes have been considered as
      potentially promising targets for anticancer immunotherapy. MAGED4 was originally
      identified as a glioma-specific antigen. Current knowledge about MAGED4
      expression in glioma is only based on mRNA analysis and MAGED4 protein expression
      has not been elucidated. In the present study, we investigated this point and
      found that MAGED4 mRNA and protein were absent or very lowly expressed in various
      normal tissues and glioma cell line SHG44, but overexpressed in glioma cell lines
      A172,U251,U87-MG as well as glioma tissues, with significant heterogeneity.
      Furthermore, MAGED4 protein expression was positively correlated with the glioma
      type and grade. We also found that the expression of MAGED4 inversely correlated
      with the overall methylation status of the MAGED4 promoter CpG island.
      Furthermore, when SHG44 and A172 with higher methylation were treated with the
      DNA demethylating agent 5-aza-2'-deoxycytidine (5-AZA-CdR) reactivation of MAGED4
      mRNA was mediated by significant demethylation in SHG44 instead of A172. However,
      5-AZA-CdR treatment had no effect on MAGED4 protein in both SHG44 and A172 cells.
      In conclusion, MAGED4 is frequently and highly expressed in glioma and is partly
      regulated by DNA methylation. The results suggest that MAGED4 might be a
      promising target for glioma immunotherapy combined with 5-AZA-CdR to enhance its
      expression and eliminate intratumor heterogeneity.

PMID- 24870748
TI  - The prostaglandin synthase 2/cyclooxygenase 2 (PTGS2/ COX2) rs5277 polymorphism
      does not influence risk of colorectal cancer in an Iranian population.
AB  - BACKGROUND: The prostaglandin-endoperoxide synthase 2 [PTGS2, commonly known as
      cyclooxygenase-2 (COX-2)] is an enzyme induced by proinflammatory stimuli that is
      often overexpressed in malignant tissue and involved in the synthesis of
      prostaglandins and thromboxanes, regulators of processes such as inflammation,
      cell proliferation, and angiogenesis, all relevant for cancer development. We
      investigated whether a functional genetic polymorphism, rs5277, in COX-2 may have
      a risk-modifying effect on sporadic colorectal cancer in an Iranian population.
      MATERIALS AND METHODS: We conducted a case-control study on 167 patients with
      colorectal cancer and 197 cancer-free controls in Taleghani Hospital in Tehran,
      Iran, between 2007 and 2011. Peripheral blood samples of both groups were
      processed for DNA extraction and genotyping of the COX-2 gene polymorphism
      (rs5277) using PCR-RFLP. RFLP results were confirmed by direct sequencing.
      Logistic regression analysis was performed to calculate the adjusted odds ratio
      (OR) and 95% confidence interval (95% CI). RESULTS: There was no significant
      difference in the distribution of COX-2 gene rs5277 polymorphism genotype and the
      allelic form, among CRC patients compared with the healthy control group (p:
      0.867). CONCLUSIONS: Our results suggest that rs5277 polymorphism in COX2 could
      not be a good prognostic indicator for patients with CRC.

PMID- 24870749
TI  - Prognostic significance of 14-3-3gamma overexpression in advanced non-small cell
      lung cancer.
AB  - The 14-3-3 protein has been shown to be involved in the cancer process. However,
      there is no understanding of the relationship between 14-3-3gamma (14-3-3 gamma)
      expression and prognosis in advanced non-small cell lung cancer. In this study,
      we therefore investigated the association between protein levels by
      immunohistochemistry and clinicopathological features of advanced NSCLC patients.
      Survival curves were estimated using the Kaplan-Meier method and tested by log
      rank. Multivariate analysis was conducted with the Cox's regression model to
      determine independence of factors. p values less than 0.05 were considered
      significant. A total 153 patients were studied, with 54.3% being stage III and
      45.8% stage IV. Fifty-one cases (33.3%) were squamous cell carcinomas, and 98
      cases (64.1%) were adenocarcinomas. High 14-3-3gamma expression was seen in 59.5%
      and significantly correlated with lymph node metastasis (p=0.010) and distant
      metastasis (p=0.017). On Kaplan-Meier analysis, high 14-3-3gamma expression was
      associated with poorer survival with a marginal trend toward significance
      (p=0.055). On multivariate analysis, age, treatment, and 14-3-3gamma expression
      proved to be independent prognostic parameters. In vitro experiments indicated
      that 14-3-3gamma overexpression also played a potential role in cancer invasion.
      In conclusion, our data suggest that 14-3-3gamma overexpression is associated
      with invasion and a poor prognosis. Therefore, 14-3-3gamma may be a potential
      prognostic marker of advanced non-small cell lung cancer.

PMID- 24870750
TI  - Comparative analysis of Oct4 in different histological subtypes of esophageal
      squamous cell carcinomas in different clinical conditions.
AB  - BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a common cancer with
      poor prognosis. It has been hypothesized that Oct4 positive radioresistant stem
      cells may be responsible for tumor recurrence. Hence, we evaluated Oct4
      expression in ESCC in pre-treatment, post neo-adjuvant residual and post-surgical
      recurrent tumours. MATERIALS AND METHODS: Endoscopic mucosal biopsies were used
      to study Oct4 expression and the observations were correlated with histological
      tumor grades, patient data and clinical background. RESULTS: All patients
      presented with dysphagia with male predominance and a wide age range. Majority of
      the patients had intake of mixed diet, history of alcohol and tobacco intake was
      documented in less than half of the patients. Oct 4 expression was significantly
      higher in poorly differentiated (PDSCC) and basaloid (BSCC) subtypes than the
      other better differentiated tumor morphology. Oct4 was also expressed by
      adjoining esophageal mucosa showing low grade dysplasia and basal cell
      hyperplasia (BCH). Biopsies in PDSCC and BSCC groups were more likely to show a
      positive band for Oct4 by polymerase chain reaction (PCR). Dysplasia and BCH
      mucosa also showed Oct4 positivity by PCR. All mucosal biopsies with normal
      morphology were negative for Oct4. Number of tissue samples showing Oct4
      positivity by PCR was higher than that by the conventional immunohistochemistry
      (p>0.05). Oct4 expression pattern correlated only with tumor grading, not with
      other parameters including the clinical background or patient data. CONCLUSIONS:
      Our observations highlighted a possible role of Oct4 in identifying putative
      cancer stem cells in ESCC pathobiology and response to treatment. The
      implications are either in vivo existence of Oct4 positive putative cancer stem
      cells in ESCC or acquisition of cancer stem cell properties by tumor cells as a
      response to treatment given, resulting ultimately an uncontrolled cell
      proliferation and treatment failure.

PMID- 24870751
TI  - Diagnostic accuracy of 18F-FDG-PET in patients with testicular cancer: a meta
      analysis.
AB  - OBJECTIVE: Fluorine-18-fluorodeoxyglucose positron emission tomography (18F-FDG
      PET) is a new technique for identifying different malignant tumors using
      different uptake values between tumor cells and normal tissues. Here we assessed
      the diagnostic accuracy of 18F-FDG-PET in patients with testicular cancer by
      pooling data of existing trials in a meta-analysis. METHODS: PubMed/MEDLINE,
      Embase and Cochrane Central Trials databases were searched and studies published
      in English relating to the diagnostic value of FDG-PET for testicular cancer were
      collected. The summary receiver operating characteristic (SROC) curve was used to
      examine the FDG-PET accuracy. RESULTS: A total of 16 studies which included 957
      examinations in 807 patients (median age, 31.1 years) were analyzed. A meta
      analysis was performed to combine the sensitivity and specificity and their 95%
      confidence intervals (CIs), from diagnostic odds ratio (DOR), positive likelihood
      ratios (PLR), negative likelihood ratio (NLR). SROC were derived to demonstrate
      the diagnostic accuracy of FDG-PET for testicular cancer. The pooled sensitivity
      and specificity were 0.75 (95% confidence interval (CI), 0.70-0.80) and 0.87 (95%
      CI, 0.84-0.89), respectively. The pooled DOR was 35.6 (95% CI, 12.9-98.3). The
      area under the curve (AUC) was 0.88. The pooled PLR and pooled NLR were 7.80 (95%
      CI, 3.73-16.3) and 0.31 (95% CI, 0.23-0.43), respectively. CONCLUSION: In
      patients with testicular cancer, 18F-FDG-PET demonstrated a high SROC area, and
      could be a potentially useful tool if combined with other imaging methods such as
      MRI and CT. Nevertheless, the literature focusing on the use of 18F-FDG-PET in
      this setting still remains limited.

PMID- 24870752
TI  - Health-related quality of life in women with breast cancer: a literature-based
      review of psychometric properties of breast cancer-specific measures.
AB  - BACKGROUND: Breast cancer is one of the most common cancers in women in the
      world. Health-related quality of life (HRQL) at treatment endpoint in cancer
      clinical trials is widely considered to be increasingly important. The aim of
      this review was to provide a literature-based assessment of the validity,
      reliability and responsiveness of breast cancer-specific HRQL instruments in
      women breast cancer patients. MATERIALS AND METHODS: The databases consulted were
      Medline, PubMed, and Embase. The inclusion criteria required studies to: (1)
      involve use of HRQL measures; (2) cover women with breast cancer under standard
      treatment (surgery, radiation therapy, chemotherapy, hormone therapy, and
      targeted therapy); (3) involve the validity, reliability, or responsiveness of
      HRQL; (4) deal with validation of breast cancer-specific HRQL instruments.
      RESULTS: A total of 16 studies were identified through the literature search that
      met the 4 inclusion criteria. Some seven instruments were assessed among these 16
      studies: EORTC QLQ-BR23, FACT-B, FACT-ES, HFRDIS, LSQ- 32, QLICP-BR, and SLDS-BC.
      EORTC QLQ-BR23, FACT-B, LSQ-32, QLICP-BR, and SLDS-BC are more general breast
      cancer-specific HRQL instruments. FACT-EB is the endocrine subscale combined with
      FACT-B in order to measure the side effects and putative benefits of hormonal
      treatment administered in breast cancer patients. HFRDIS is the HRQL measure
      focusing on hot flash concerns. CONCLUSIONS: This paper provides an overall
      understanding on the currently available breast cancer-specific HRQL instruments
      in women breast cancer patients.

PMID- 24870753
TI  - Clinicopathologic features and prognosis of osteosarcoma in Turkish adults.
AB  - BACKGROUND: Osteosarcomas are the most common solid malignancies of bone. In the
      last two decades there have been no concrete developments in their systemic
      treatment. In this trial we aimed to present our osteosarcoma patient clinical
      and demographic outcomes. MATERIALS AND METHODS: Patients treated and followed up
      for osteosarcoma in Ankara Numune Education and Research Hospital from 2002 to
      2012 were reviewed retrospectively. RESULTS: A total of 21 patients (15 male, 6
      female) were diagnosed with osteosarcoma. The disease was located at extremities
      in 76% and in 14% was metastatic at the time of diagnosis. Median disease free
      survival (DFS) was 36 months in non-metastatic patients and median progression
      free survival (PFS) was 2 months in metastatic patients (p<0.0001). Median
      overall survival (OS) was 80 months and 4 months, respectively (p=0.012). There
      were no survival differences in terms of presentation with pathological fracture,
      tumor size, tumor grade, alkaline phosphatase and lactate dehydrogenase level and
      type of chemotherapy regimen. CONCLUSIONS: Tumor site and stages are the most
      important prognostic factors for osteosarcoma. Extremity primary tumors have
      beter survival rates than non-extremity tumors. As a result of the use of
      effective chemotherapy the long term survival rates have improved from 10-20% to
      60-70% in the last decades but we need more active agents, especially for
      metastatic cases.

PMID- 24870754
TI  - Molecular genetic studies on 167 pediatric ALL patients from different areas of
      Pakistan confirm a low frequency of the favorable prognosis fusion oncogene TEL
      AML1 (t 12; 21) in underdeveloped countries of the region.
AB  - TEL-AML1 fusion oncogene (t 12; 21) is the most common chromosomal abnormality in
      childhood acute lymphoblastic leukemia (ALL). This translocation is associated
      with a good prognosis and rarely shows chemotherapeutic resistance to 3-drug
      based remission induction phase of treatment as well as overall treatment. Thus,
      the higher the frequency of this fusion oncogene, the easier to manage childhood
      ALL in a given region with less intensive chemotherapy. Although global frequency
      of TEL-AML1 has been reported to be 20-30%, a very low frequency has been found
      in some geographical regions, including one study from Lahore, Punjab, Pakistan
      and others from India. The objective of present study was to investigate if this
      low frequency of TEL- AML1 in pediatric ALL is only in Lahore region or similar
      situation exists at other representative oncology centers of Pakistan. A total of
      167 pediatric ALL patients were recruited from major pediatric oncology centers
      situated in Lahore, Faisalabad, Peshawar and Islamabad. Patients were tested for
      TEL-AML1 using nested reverse transcription polymerase chain reaction (RT-PCR).
      Only 17 out of 167 (10.2%) patients were found to be TEL-AML1 positive. TEL
      AML1+ALL patients had favorable prognosis, most of them (82.4%, 14/17) showing
      early remission and good overall survival. Thus, our findings indicate an overall
      low frequency of TEL-AML1 in Pakistan pediatric ALL patients, in accordance with
      lower representation of this prognostically important genetic abnormality in
      other less developed countries, specifically in south Asia, thus associating it
      with poor living standards in these ethnic groups. It also indicates ethnic and
      geographical differences in the distribution of this prognostically important
      genetic abnormality among childhood ALL patients, which may have a significant
      bearing on ALL management strategies in different parts of the world. 

PMID- 24870755
TI  - Prognostic value of pretreatment serum alkaline phosphatase in nasopharyngeal
      carcinoma.
AB  - BACKGROUND: The prognostic value of serum alkaline phosphatase (S-ALP) has not
      been fully validated for nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: S
      ALP levels were measured in 601 patients newly diagnosed with NPC before radical
      treatment, and possible associations of these levels with 5-year overall survival
      (OS) and tumor-free survival (TFS) were explored using univariate and
      multivariate analyses. RESULTS: Elevated pretreatment S-ALP (>85 U/L) was
      significantly less frequent among patients classified as T1+2 or stage I+II than
      among those classified as T3+4 or stage III+IV. Multivariate analysis showed that
      elevated pretreatment S-ALP (>85 U/L), age, T classification and N stage were
      independent predictors of poor OS and TFS. CONCLUSIONS: Pretreatment S-ALP may be
      a reliable biomarker to evaluate the long-term prognosis of patients with NPC.

PMID- 24870756
TI  - Associations between mammography and ultrasound imaging features and molecular
      characteristics of triple-negative breast cancer.
AB  - BACKGROUND: The triple-negative breast cancer (TNBC) is an aggressive cancer
      characterized by the absence of estrogen receptor (ER), progesterone receptor
      (PR) and human epidermal growth factor receptor 2 (HER2). Preoperative
      mammography and ultrasound features of TNBC may potentially suggest
      characteristics of the disease and assist in treatment decisions. MATERIALS AND
      METHODS: The study covered 153 patients with TNBC from May 2011 to May 2012 who
      were confirmed by postoperative pathology results in our hospital. We compared
      the radiological findings among the patients and sought to determine the
      significant iconographic features. The biomarkers p53 and Ki-67 are regarded as
      significant factors in TNBC. They were therefore used to divide the TNBC into
      four groups for assessment of relationships with TNBC imaging features. RESULTS:
      On mammography, most TNBCs exhibit obscure (44.3%) masses. On ultrasound, the
      majority of masses (95.4%) were predominantly indistinct (50.7%), irregular
      (76.0%) or featuring posterior echo enhancement/shadowing. Color Doppler flow
      imaging (CDFI) emphasized hypervascular (32.9%) masses. Differences in CDFI by
      ultrasound among the four groups were statistically significant (p=0.009). There
      were obvious differences in the percentages of spiculated margin (p=0.049) and
      intensive posterior echo (p=0.006) with spotty flow imaging by ultrasound between
      the Ki-67 (+) p53 (+) and other groups. CONCLUSIONS: A combination of mammography
      and ultrasound revealed the imaging characteristics of TNBC included an obscure
      mass with less attenuated posterior echoes and some vascularity. A worse
      prognosis was associated with spiculated margin and intensive posterior echoes
      with spotty flow imaging.

PMID- 24870757
TI  - Reirradiation with robotic stereotactic body radiotherapy for recurrent
      nasopharyngeal carcinoma.
AB  - BACKGROUND: Recurrent nasopharyngeal carcinoma (NPC) after previous radiotherapy
      is challenging. There is no standard approach for salvage treatment. Here we
      present toxicity and treatment results for recurrent NFC patients who underwent
      fractionated stereotactic radiotherapy (FSRT) as second line radiotherapy (RT).
      MATERIALS AND METHODS: Between April 2009 and July 2012, 24 patients, with a male
      to female ratio of 3:1, were treated with CykerKnife(r) FSRT for recurrent NFC in
      our institution. Seven out of 24 patients had metastatic recurrent disease.
      Median age was 53 years (range, 20-70 years). Initial RT dose was 70Gy. The time
      period between initial RT and FSRT was a median of 33.2 months. The median
      prescription dose for FSRT was 30Gy (range, 24-30 Gy) in a median of 5 fractions
      (range, 4-6). RESULTS: The median follow-up for all patients was 19.5 months
      (IQR: 12.2. -29.2 months). The locoregional control; progression free survival
      and overall survival (OS) rates for 1-, 2- and 3-year were 64%, 38%, 21%; 60%,
      30%, 17% and 83%, 43%, 31%, respectively. Median OS for the entire cohort was 22
      months (95% CI: 16.5-27.5). On multivariate analysis recurrent tumor stage was
      the only prognostic factor for OS (p=0.004). One patient exhibited grade III
      temporal lobe necrosis. One died because of grade IV mucositis and overlapping
      infection. CONCLUSIONS: The treatment of recurrent NPC is controversial.
      Fractionated stereotactic radiotherapy is promising. However, the published
      trials are heterogeneous with respect to the selection criteria and treatment
      details. Prospective studies with long term follow-up data are warranted.

PMID- 24870759
TI  - Survival of brain metastatic patients in Yazd, Iran.
AB  - BACKGROUND: Brain metastasis occurs when cancerous cells come from a known (or
      sometimes an unknown) primary tumor to the brain and implant and grow there. This
      event is potentially lethal and causes neurologic symptoms and signs. These
      patients are treated in order to decrease their neurologic problems, increase
      quality of life and overall survival. MATERIALS AND METHODS: In this study we
      evaluated clinical characteristics of 206 patients with brain metastases referred
      to our center from 2004 to 2011. RESULTS: The mean age was 53.6 years. The
      primary tumors were breast cancer (32%), lung cancer (24.8%), lymphoma (4.4%),
      sarcoma (3.9%), melanoma (2.9%), colorectal cancer (2.4%) and renal cell
      carcinoma (1.5%). In 16.5% of the patients, brain metastasis was the first
      presenting symptom and the primary site was unknown. Forty two (20.4%) patients
      had a single brain metastasis, 18 patients (8.7%) had two or three lesions, 87
      (42.2%) patients had more than three lesions. Leptomeningeal involvement was seen
      in 49 (23.8%) patients. Thirty five (17%) had undergone surgical resection. Whole
      brain radiation therapy was performed for all of the patients. Overall survival
      was 10.1 months (95%CI; 8.65-11.63). One and two year survival was 27% and 12%
      respectively. CONCLUSIONS: Overall survival of patients who were treated by
      combination of surgery and whole brain radiation therapy was significantly better
      than those who were treated with whole brain radiation therapy only [13.8 vs 9.3
      months (p=0.03)]. Age, sex, primary site and the number of brain lesions did not
      show significant relationships with overall survival.

PMID- 24870758
TI  - Epidemiology and survival of hepatocellular carcinoma in the central region of
      Thailand.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common cancers in
      men and the third most common cancer in woman in Thailand. This retrospective
      study was designed to assess the prevalence, clinical manifestations, treatment
      outcomes and prognosis of HCC in the central region of Thailand. MATERIALS AND
      METHODS: The authors retrospectively reviewed all HCC patients aged more than 15
      years old in Thammasat university hospital (TUH) during the period from January
      2007 to December 2012. Clinical information, biochemical tests and radiologic
      findings were collected from review of medical records. RESULTS: There were 308
      patients with HCC, which accounted for the prevalence of 5.19% of all cancers
      diagnosed in TUH during the study period. Of these, 125 (40.5%) had complete
      information retrievable from their medical records and met the inclusion
      criteria, 99 (79.2%) were males. The mean age was 57.4 years. A quarter of HCC
      patients in this study presented without any symptom before diagnosis. The common
      clinical presentations in the remaining patients were hepatomegaly 64/125
      (51.2%), abdominal pain 56/125 (44.8%) and ascites 16/125 (20.8%). Cirrhosis was
      seen in almost all patients (92.8%). The most common causes of HCC in this study
      were chronic hepatitis B (49.6%) and C (19.2%). Based on Barcelona Clinic Liver
      Cancer staging, 75.4% presented at intermediate or late stage. Patients receiving
      curative therapy with either surgical treatment or radiofrequency ablation had
      significantly longer survival time after the HCC diagnosis than the palliative
      therapy group (11.0 months vs 4.0 months, p value= 0.004). The mean survival time
      after the HCC diagnosis was 10.5 months. CONCLUSIONS: The common causes of HCC in
      central region of Thailand were chronic hepatitis B and C. Surgical therapy or
      RFA seemed to provide better outcomes than other treatments but only in patients
      with early stage lesions. Most of the patients in this study presented with
      advanced diseases and had grave prognosis. Appropriate screening patients at risk
      for HCC might be an appropriate way to achieve early diagnosis and improve the
      treatment outcome.

PMID- 24870760
TI  - Staurosporine induced apoptosis rapidly downregulates TDP- 43 in glioma cells.
AB  - TDP-43 is a ubiquitously expressed DNA/RNA binding protein that has recently
      attracted attention for its involvement in neurodegenerative diseases. While TDP
      43 has been found to participate in various important cellular activities
      including stress and apoptosis, little is known about its role in cancer cells.
      Here we report that staurosporine (STS) induced apoptosis in U87 glioma cells is
      associated with rapid downregulation of TDP-43 at both mRNA and protein levels.
      The latter is dependent on activation of caspase 3. More importantly, we have
      shown that knockdown of TDP-43 by specific siRNA dramatically enhanced
      cytotoxicity of STS. These results suggest that normal level of TDP-43 may be
      protective for cancer cells under apoptotic insult. 

PMID- 24870761
TI  - Anti-proliferation effects and molecular mechanisms of action of
      tetramethypyrazine on human SGC-7901 gastric carcinoma cells.
AB  - AIM: To investigate the effects of tetramethypyrazine (TMP) on proliferation and
      apoptosis of the human gastric carcinoma cell line 7901 and its possible
      mechanism of action. METHODS: The viability of TMP-treated 7901 cells was
      measured with a 3-(4, 5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide
      assay (MTT) and cell apoptosis was analyzed by flow cytometry. The distribution
      of cells in different phases of cell cycle after exposure of TMPs was analyzed
      with flow cytometry. To investigate the molecular mechanisms of TMP-mediated
      apoptosis, the expression of NF-xBp65, cyclinD1 and p16 in SGC-7901 cells was
      analyzed by reverse transcription- polymerase chain reaction (RT-PCR) and western
      blotting. RESULTS: TMP inhibited the proliferation of human gastric carcinoma
      cell line 7901 in dose and time dependent manners. Cell growth was suppressed by
      TMP at different concentrations (0.25, 0.5, 1.0, 2.0 mg/ml), the inhibition rate
      is 0.46%, 4.36%, 14.8%, 76.1% (48h) and 15.5%, 18.5%, 41.2%, 89.8% (72h)
      respectively. When the concentration of TMPs was 2.0mg/ml, G1-phase arrest in the
      SGC-7901 cells was significant based on the data for cell cycle distribution. RT
      PCR demonstrated that NF-xBp65 and cyclin D1 mRNA expression was significantly
      down-regulated in 7901 cells treated with 2.0 mg/ml TMP for 72h (p<0.05), while
      the p16 mRNA level was up-regulated (p<0.05). The protein expression of NF-xBp65
      and cyclin D1 decreased gradually with the increase in TMP concentration,
      compared with control cells (p<0.05), while expression of protein p16 was up
      regulated (p<0.01). CONCLUSION: TMP exhibits significant anti-proliferative and
      pro-apoptotic effects on the human gastric carcinoma cell line SGC-7901. NF
      xBp65, cyclinD1 and p16 may also play important roles in the regulation
      mechanisms.

PMID- 24870763
TI  - Parents' and health-care providers' perspectives on side- effects of childhood
      cancer treatment in Indonesia.
AB  - BACKGROUND: Efficacy of childhood cancer treatment in low-income countries may be
      impacted by parents' and health-care providers' perspectives on chemotherapy
      related side-effects. This study explores prevalence and severity of side-effects
      in childhood cancer, and compares health beliefs about side-effects between
      parents and health-care providers, and between nurses and doctors in Indonesia.
      MATERIALS AND METHODS: Semi-structured questionnaires were filled in by 40
      parents and 207 health-care providers in an academic hospital. RESULTS: Parents
      exporessed a desire to receive more information about side-effects (98%) and
      worried about this aspect of treatment (90%), although side-effects were less
      severe than expected (66%). The most frequent was behavior alteration (98%) and
      the most severe was hair loss. Only 26% of parents consulted doctors about side
      effects. More parents, compared to health-care providers, believed that medicines
      work better when side-effects are more severe (p<0.001), and accepted severe side
      effects (p=0.021). More health-care providers, compared to parents, believed that
      chemotherapy can be stopped or the dosage altered when there are side-effects
      (p=0.011). More nurses, compared to doctors, stated that side-effects were
      unbearable (p=0.004) and made them doubt efficacy of treatment (p<0.001).
      CONCLUSIONS: Behavior alteration is the most frequent and hair loss the most
      severe side-effect. Apparent discrepancies in health beliefs about side-effects
      exist between parents and health-care providers. A sustainable parental education
      program about side-effects is recommended. Health-care providers need to update
      and improve their knowledge and communication skills in order to give appropriate
      information. Such measures may improve outcome of childhood cancer treatment in
      low-income countries, where adherence to therapy is a major issue.

PMID- 24870762
TI  - Hematologic toxicity in patients undergoing radical anti- cancer therapy: a cross
      sectional analysis of patients in an oncology ward in India.
AB  - Burden of cancer is progressively increasing in developing countries like India
      which has also led to a steep rise in toxicity due to anti-cancer therapy. A
      cross-sectional analysis was here conducted for patients with different
      malignancies (except leukaemia) who while undergoing radical anti-cancer therapy
      were admitted to our oncology ward from January-July 2013. In a total of 280
      patients, the total number of toxicity events was 473. Nine patients expired over
      this time period. Among the events, grade 2 anaemia the most common (n=189) while
      the most common grades of neutropenia and thrombocytopenia were grade 4 (n=114)
      and grade 2 (n=48), respectively. Among the tracable microbial etiologies, gram
      negative bacteria were the most commonly found pathogens. Treatment interruptions
      took place in 240 patients (median duration=8.8 days). Prolonged hospital
      admission, intensive care and artificial ventilation support was needed to be
      given in 48, 7 and 13 patients respectively. Advanced NSCLC, KPS <70,
      pancytopenia and artificial ventilation requirement were found to have a
      significant impact on death. Such studies show the prevailing practice from
      institutes of our country and may guide us formulating a guideline for managing
      such toxicities for this part of the world. 

PMID- 24870764
TI  - Inferring single nucleotide polymorphisms in microRNA binding sites of lung
      cancer-related inflammatory genes.
AB  - Single nucleotide polymorphisms located at microRNA (miRNA)-binding sites are
      likely to affect the expression of miRNA targets and may contribute to the
      susceptibility of humans to common diseases. Here 335 candidate lung cancer
      related inflammatory genes were selected according to the existing literature and
      database. We identified putative miRNA-binding sites of 149 genes by specialised
      algorithms and screened SNPs in the 3'UTRs of these genes. By calculating binding
      free energy, we sorted 269 SNPs on the basis of the possibility of prediction.
      The proposed approach could help to easy the identification of functionally
      relevant SNPs and minimize the workflow and the costs. 

PMID- 24870765
TI  - The CCND1 G870A gene polymorphism and brain tumor risk: a meta-analysis.
AB  - BACKGROUND: In recent years, numerous studies have been performed to investigate
      the CCND1 G870A gene polymorphism impact on brain tumors susceptibility.
      Unfortunately, the results of previous studies were inconsistent. Therefore, we
      performed a meta-analysis to derive a more precise estimation of any association.
      MATERIALS AND METHODS: We conducted a search in PubMed, Embase and CNKI covering
      all published papers up to November, 2013. Odds ratios (ORs) and their 95%
      confidence intervals (95%CIs) were applied to assess associations. RESULTS: A
      total of 6 publications including 9 case-control studies met the inclusion
      criteria. The pooled ORs for the total included studies showed significant
      association among comparison A vs G (OR= 1.246, 95%CI= 1.092-1.423, p= 0.001),
      homozygote comparison AA vs GG (OR= 1.566, 95%CI= 1.194-2.054, p= 0.001),
      heterozygote comparison AG vs GG (OR= 1.290, 95%CI= 0.934-1.782, p= 0.122),
      dominant model AA/GA vs GG (OR= 1.381, 95%CI= 1.048-1.821, p= 0.022) and
      recessive model AA vs GA/GG (OR= 1.323, 95%CI= 1.057- 1.657, p= 0.015) especially
      in glioma. CONCLUSIONS: CCND1 G870A polymorphism may increase brain tumor risk,
      especially for gliomas. However, more primary large scale and well-designed
      studies are still required to evaluate the interaction of CCND1 G870A
      polymorphism with brain tumor risk.

PMID- 24870766
TI  - Stathmin is a marker of progression and poor prognosis in esophageal carcinoma.
AB  - Stathmin, also called oncoprotein 18, is a founding member of the family of
      microtubule-destabilizing proteins that play a critical role in the regulation of
      mitosis. At the same time stathmin has been recognized as one of responsible
      factors in cancer cells. The aim of this study was to assess stathmin status, its
      correlations with clinicopathological parameters and its role as a progosnostic
      marker in EC patients. The protein and mRNA levels of stathmin were examined by
      immunohistochemistry (IHC) and in situ hybridization in 100EC tissues and
      adjacent noncancerous tissues. mRNA and protein expression of stathmin in three
      EC cell lines(EC9706, ECa109, EC1 commonly used in research) were also analyzed
      using immunocytochemistry, western blot and in situ hybridization. The prognostic
      value of Stathmin expression within the tumor tissues were assessed by Cox
      regression and Kaplan-Meier analysis. We showed that stathmin expression was
      significantly higher in EC tissues than in adjacent noncancerous tissues. High
      stathmin immunostaining score in the EC was positively correlated with tumor
      differentiation, Tumor invasion, Lymph node metastases, and TNM stage. In
      addition, we demonstrated that three EC cell lines examined, were constitutively
      expressing a high level of stathmin. Of those, EC-1 showed the strongest mRNA and
      protein expression for the stathmin analyzed. Kaplan-Meier analysis showed that
      significantly longer 5-year survival rate was seen in EC patients with high
      Stathmin expression, compared to those with low expression of Stathmin
      expression. Furthermore, multivariate Cox proportional hazard analyses revealed
      that Stathmin was an independent factors affecting the overall survival
      probability. In conclusion, our data provide a basis for the concept that
      stathmin might be associated with EC development and progression.. High levels of
      Stathmin expression in the tumor tissues may be a good prognostic marker for
      patients with EC.

PMID- 24870767
TI  - Vaginal dose, toxicity and sexual outcomes in patients of cervical cancer
      undergoing image based brachytherapy.
AB  - BACKGROUND: The aim of the study was to evaluate the vaginal dose and toxicity in
      patients of cervical cancer treated with image guided brachytherapy at our
      institute. MATERIALS AND METHODS: Thirty-five patients treated with image based
      brachytherapy for cervical cancer were included. Vaginal contouring was done on
      MRI at brachytherapy and with CT scans of subsequent brachytherapy fractions.
      Dose volume parameters (DVH) were reported in accordance with the GEC-ESTRO
      guidelines. These were correlated with vaginal toxicity (assessed by CTCAE
      version 3) and quality of sexual life assessed at one year of completion of
      treatment. RESULTS: Vaginal shortness was observed in 22 out of 30 (62.8%)
      patients, Nine (25.7%) had vaginal dryness and in 10 (28.5%) patients, there was
      contact bleeding. No association could be demonstrated between the dose volume
      parameters and vaginal toxicity in the present study. CONCLUSIONS: The lack of
      association between dose volume parameters of vagina with vaginal morbidity may
      be due to uncertainties involved in the delineation of vaginal wall and
      dosimetry. Future research is required to accurately define vaginal dose
      distribution to study its correlation with vaginal morbidity. Vaginal morbidity
      needs to be documented in order to improve the sexual outcome in these patients.

PMID- 24870769
TI  - CCDC26 gene polymorphism and glioblastoma risk in the Han Chinese population.
AB  - BACKGROUND: Glioblastoma (GBM) is an immunosuppressive tumor whose median
      survival time is only 12- 15 months, and patients with GBM have a uniformly poor
      prognosis. It is known that heredity contributes to formation of glioma, but
      there are few genetic studies concerning GBM. MATERIALS AND METHODS: We genotyped
      six tagging SNPs (tSNP) in Han Chinese GBM and control patients. We used
      Microsoft Excel and SPSS 16.0 statistical package for statistical analysis and
      SNP Stats to test for associations between certain tSNPs and risk of GBM in five
      different models. ORs and 95%CIs were calculated for unconditional logistic
      regression analysis with adjustment for age and gender. The SHEsis software
      platform was applied for analysis of linkage disequilibrium, haplotype
      construction, and genetic associations at polymorphism loci. RESULTS: We found
      rs891835 in CCDC26 to be associated with GBM susceptibility at a level of
      p=0.009. The following genotypes of rs891835 were found to be associated with GBM
      risk in four different models of gene action: i) genotype GT (OR=2.26; 95%CI,
      1.29-3.97; p=0.019) or GG (OR=1.33; 95%CI, 0.23-7.81; p=0.019) in the codominant
      model; ii) genotypes GT and GG (OR=2.18; 95%CI, 1.26-3.78; p=0.0061) in the
      dominant model; iii) GT (OR=2.24; 95%CI, 1.28-3.92; p=0.0053) in the overdominant
      model; iv) the allele G of rs891835 (OR=1.85; 95%CI, 1.14-3.00; p=0.015) in the
      additive model. In addition, "CG" and "CGGAG" were found by haplotype analysis to
      be associated with increased GBM risk. In contrast, genotype GG of CCDC26
      rs6470745 was associated with decreased GBM risk (OR=0.34; 95%CI, 0.12-1.01;
      p=0.029) in the recessive model. CONCLUSIONS: Our results, combined with those
      from previous studies, suggest a potential genetic contribution of CCDC26 to GBM
      progression among Han Chinese.

PMID- 24870768
TI  - Multicenter analysis of gestational trophoblastic neoplasia in Turkey.
AB  - BACKGROUND: To evaluate the incidence, diagnosis and management of GTN among 28
      centers in Turkey. MATERIALS AND METHODS: A retrospective study was designed to
      include GTN patients attending 28 centers in the 10-year period between January
      2003 and May 2013. Demographical characteristics of the patients,
      histopathological diagnosis, the International Federation of Gynecology and
      Obstetrics (FIGO) anatomical and prognostic scores, use of single-agent and multi
      agent chemotherapy, surgical interventions and prognosis were evaluated. RESULTS:
      From 2003-2013, there were 1,173,235 deliveries and 456 GTN cases at the 28
      centers. The incidence was calculated to be 0.38 per 1,000 deliveries. According
      to the evaluated data of 364 patients, the median age at diagnosis was 31 years
      (range, 15-59 years). A histopathological diagnosis was present for 45.1% of the
      patients, and invasive mole, choriocarcinoma and PSTTs were diagnosed in 22.3%
      (n=81), 18.1% (n=66) and 4.7% (n=17) of the patients, respectively. Regarding
      final prognosis, 352 (96.7%) of the patients had remission, and 7 (1.9%) had
      persistence, whereas the disease was mortal for 5 (1.4%) of the patients.
      CONCLUSIONS: Because of the differences between countries, it is important to
      provide national registration systems and special clinics for the accurate
      diagnosis and treatment of GTN.

PMID- 24870770
TI  - Induced abortion and breast cancer: results from a population-based case control
      study in China.
AB  - AIM: To determine whether induced abortion (IA) increases breast cancer (BC)
      risk. MATERIALS AND METHODS: A population-based case-control study was performed
      from Dec, 2000 to November, 2004 in Shanghai, China, where IA could be verified
      through the family planning network and client medical records. Structured
      questionnaires were completed by 1,517 cases with primary invasive epithelial
      breast cancer and 1,573 controls frequency- matched to cases for age group. The
      information was supplemented and verified by the family planning records.
      Statistical analysis was conducted with SAS 9.0. RESULTS: After adjusting for
      potential confounders, induced abortions were not found to be associated with
      breast cancer with OR=0.94 (95%CI= 0.79-1.11). Compared to parous women without
      induced abortion, parous women with 3 or more times induced abortion (OR=0.66,
      95%CI=0.46 to 0.95) and women with 3 or more times induced abortion after the
      first live birth (OR=0.66, 95%CI =0.45 to 0.97) showed a lower risk of breast
      cancer, after adjustment for age, level of education, annual income per capita,
      age at menarche, menopause, parity times, spontaneous abortion, age at first live
      birth, breast-feeding, oral contraceptives, hormones drug, breast disease, BMI,
      drinking alcohol, drinking tea, taking vitamin/calcium tablet, physical activity,
      vocation, history of breast cancer, eating the bean. CONCLUSIONS: The results
      suggest that a history of induced abortions may not increase the risk of breast
      cancer.

PMID- 24870771
TI  - Positive effects of oral beta-glucan on mucositis and leukopenia in colorectal
      cancer patients receiving adjuvant FOLFOX-4 combination chemotherapy.
AB  - The present study aimed to determine the effect of oral beta-glucan on mucositis
      and leukopenia in 62 consecutive patients with colorectal cancer treated with an
      adjuvant FOLFOX-4 regimen. The patients were retrospectively evaluated in 2
      groups: one group received beta-glucan and the other did not (control group).
      Leucocytes, neutrophils, and platelets were evaluated before and 1 week after
      chemotherapy and oral mucositis and diarrhea were noted. Leucocyte and neutrophil
      counts after chemotherapy in the beta-glucan group were 7,300/mm3 and 3,800/mm3,
      respectively, and the reductions, as compared to baseline, were not significant
      (p=0.673 and 0.784). The median platelet count was 264,000/mm3 after chemotherapy
      in the beta-glucan group and the reduction, as compared to baseline, was
      borderline significant (p=0.048). In the control group, reduction in leucocyte,
      neutrophil, and platelet counts was statistically significant. Oral mucositis and
      diarrhea were less common in the beta-glucan group. We conclude that beta-glucan
      can be used to reduce the adverse effects of chemotherapy. 

PMID- 24870772
TI  - Third-line hormonal therapy to treat prostate cancer relapse after initial and
      second-line hormonal therapy: report of 52 cases and literature review.
AB  - The aim of this study was to evaluate the efficacy of third-line combined
      androgen blockade (CAB) therapy for castration-resistant prostate cancer that
      relapsed after primary and second-line CAB. We retrospectively reviewed the
      medical records of 52 patients who received first-, second-, and third-line CAB
      therapy (medical or surgical castration, plus steroidal antiandrogen of
      chlormadinone acetate, or nonsteroidal antiandrogen of flutamide or
      bicalutamide). For cumulative analysis, we searched the PubMed database and
      identified a total of 50 cases published in English. Including our cases, this
      provided a total of 102 cases for analysis. In our study cohort, 11 cases (21.2%)
      achieved more than 50% reduction of serum prostate-specific antigen (PSA) on
      initiation of third-line CAB. We found that third-line CAB with nonsteroidal
      antiandrogen after second-line CAB with steroidal antiandrogen exhibited
      favorable results, with a positive response in six of 13 patients (46.2%).
      Cumulative analysis findings were comparable. Regarding the timing of third-line
      CAB administration, 15 patients had started at a PSA equal to or less than 4.0
      ng/ml, and eight of them (53.3%) showed a positive response to treatment,
      compared to only three of 37 patients (8.1%) whose PSA at the initiation of third
      line therapy was higher than 4.0 ng/ml (p<0.001). We conclude that third-line CAB
      with nonsteroidal antiandrogen would be particularly useful for patients whose
      cancer progressed after second-line CAB with steroidal antiandrogen. The timing
      of treatment seems to be important because the higher the PSA at the start of
      third-line therapy, the lower the PSA response rate. 

PMID- 24870773
TI  - Schedule-dependent effects of kappa-selenocarrageenan in combination with
      epirubicin on hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) has a relatively higher incidence in many
      countries of Asia. Globally, HCC has a high fatality rate and short survival.
      Epirubicin, a doxorubicin analogue, may be administered alone or in combination
      with other agents to treat primary liver cancer and metastatic diseases. However,
      the toxic effects of epirubicin to normal tissues and cells have been one of the
      major obstacles to successful cancer chemotherapy. Here, we investigated the
      effects of epirubicin in combination with kappa-selenocarrageenan on mice with
      H22 implanted tumors and HepG-2 cell proliferation, immune organ index,
      morphology, cell cycle and related protein expressions in vivo and in vitro with
      sequential drug exposure. The inhibitory rate of tumor growth in vivo was
      calculated. Drug sensitivity was measured by MTT assay, and the King's principle
      was used to evaluate the interaction of drug combination. Morphological changes
      were observed by fluorescent microscopy. Cell cycle changes were analyzed by flow
      cytometry. Expression of cyclin A, Cdc25A and Cdk2 were detected by Western
      blotting. In vivo results demonstrated that the inhibitory rate of EPI combined
      with KSC was higher than that of KSC or EPI alone, and the Q value indicated an
      additive effect. In addition, KSC could significantly raise the thymus and spleen
      indices of mice with H22 implanted tumors. In the drug sensitivity assay in
      vitro, exposure to KSC and EPI simultaneously was more effective than exposure
      sequentially in HepG-2 cells, while exposure to KSC prior to EPI was more
      effective than exposure to EPI prior to KSC. Q values showed an additive effect
      in the simultaneous group and antagonistic effects in the sequential groups.
      Morphological analysis showed similar results to the drug sensitivity assay. Cell
      cycle analysis revealed that exposure to KSC or EPI alone arrested the cells in S
      phase in HepG-2 cells, exposure to KSC and EPI simultaneously caused accumulation
      in the S phase, an effect caused by either KSC or EPI. Expression of cyclin A,
      Cdc25A and Cdk2 protein was down-regulated following exposure to KSC and EPI
      alone or in combination, exposure to KSC and EPI simultaneously resulting in the
      lowest values. Taken together, our findings suggest that KSC in combination with
      EPI might have potential as a new therapeutic regimen against HCC.

PMID- 24870774
TI  - Different immunology mechanisms of Phellinus igniarius in inhibiting growth of
      liver cancer and melanoma cells.
AB  - To assess inhibition mechanisms of a Phellinus igniarius (PI) extract on cancer,
      C57BL/6 mice were orally treated with PI extractive after or before implanting
      H22 (hepatocellular carcinoma ) or B16 (melanoma) cells. Mice were orally gavaged
      with different doses of PI for 36 days 24h after introduction of H22 or B16
      cells. Mice in another group were orally treated as above daily for 42 days and
      implanted with H22 cells on day 7. Then the T lymphocyte, antibody, cytokine,
      LAK, NK cell activity in spleen, tumor cell apoptosis status and tumor inhibition
      in related organs, as well as the expression of iNOS and PCNA in tumor tissue
      were examined. The PI extract could improve animal immunity as well as inhibit
      cancer cell growth and metastasis with a dose-response relationship. Notably,
      PI's regulation with the two kinds of tumor appeared to occur in different ways,
      since the antibody profile and tumor metastasis demonstrated variation between
      animals implanted with hepatocellular carcinoma and melanoma cells. 

PMID- 24870775
TI  - Novel mutations of the PARP-1 gene associated with colorectal cancer in the Saudi
      population.
AB  - BACKGROUND: Colorectal cancer (CRC) is the third most common type of cancers and
      the fourth leading cause of death worldwide. In Saudi Arabia, CRC accounts for
      8.5% of all tumors; it ranks first among all cancers in males and third among
      females. The aim of this study was to link between different PARP-1 mutations and
      risk of CRC in Saudi population and to determine common variants of PARP-1 in
      Saudi CRC patients and normal individuals. MATERIALS AND METHODS: DNA samples
      were isolated from fifty CRC patients and from a comparable number of control
      subjects then sequenced to detect different variations present in exons 3, 17,
      and 21 of the PARP-1 gene. RESULTS AND CONCLUSIONS: When comparing the genotype
      and allele frequencies of all detected SNPs in CRC patients with those in
      controls, we found none were significantly different for all variants even the
      most common SNP in PARP-1 gene (Val762Ala). However, two novel alterations in
      exon 21 were found to be associated with increased risk of CRC. The variants
      identified as (1) Lys933Asn [p-value 0.0318] and (2) Lys945Asn [p-value 0.0257].
      Our results suggest that PARP-1 Lys933Asn and Lys945Asn alterations could be
      associated with increased risk of CRC in the Saudi population.

PMID- 24870776
TI  - Population based study of the association between binge drinking and mortality
      from cancer of oropharynx and esophagus in Korean men: the Kangwha cohort study.
AB  - We assessed the association between frequency of heavy binge drinking and
      mortality from oropharynx and esophagus cancer after controlling for the total
      volume of alcohol intake among Korean men. The cohort comprised 2,677 male
      residents in Kangwha County, aged 55 or older in March 1985, for their upper
      digestive tract cancer mortality for 20.8 years up to December 31, 2005. For
      daily binge drinkers versus non-drinkers, the hazard ratios (95% Cls) for
      mortality were 4.82 (1.36, 17.1) and 6.75 (1.45, 31.4) for oropharyngeal and
      esophageal cancers, respectively. Even after adjusting for the volume of alcohol
      intake, we found the hazard ratios for frequency of binge drinking and mortality
      of oropharyngeal or esophageal cancer to not change appreciably: the hazard
      ratios were 4.90 (1.00, 27.0) and 7.17 (1.02, 50.6), respectively. For esophageal
      cancer, there was a strong dose-response relationship. The frequency of heavy
      binge drinking and not just the volume of alcohol intake may increase the risk of
      mortality from upper digestive tract cancer, particularly esophageal cancer in
      Korean men. These findings need to be confirmed in further studies with a larger
      sample size. 

PMID- 24870777
TI  - Preparation of selenium-enriched Bifidobacterium longum and its effect on tumor
      growth and immune function of tumor-bearing mice.
AB  - In this study, we demonstrated selenium (Se) accumulation in Bifidobacterium
      longum strain (B. longum) and evaluated the effect of Se-enriched B. longum (Se
      B. longum) on tumor growth and immune function in tumor-bearing mice. Analysis
      using high-performance liquid chromatography-inductively coupled plasma mass
      spectrometry (HPLC-ICP-MS) revealed that more than 99% of Se in Se-B. longum was
      organic, the main component of which was selenomethionine (SeMet). In the in vivo
      experiments, tumor-bearing mice (n=8) were orally administrated with different
      doses of Se-B. longum alone or combined with cyclophosphamide (CTX). The results
      showed that the middle and high dose of Se-B. longum significantly inhibited
      tumor growth. When Se-B. longum and CTX were combined, the antitumor effect was
      significantly enhanced and the survival time of tumor-bearing mice (n=12) was
      prolonged. Furthermore, compared with CTX alone, the combination of Se-B. longum
      and CTX stimulated the activity of natural killer (NK) cells and T lymphocytes,
      increasing the levels of interleukin-2 (IL-2) and tumor necrosis factor-alpha
      (TNF-alpha), and the leukocyte count of H22 tumor-bearing mice (n=12).

PMID- 24870778
TI  - How to explain the contradiction of microRNA 200c expression and survival in
      solid tumors? A meta-analysis.
AB  - MicroRNA 200c is a microRNA 200 family member that plays an important role in
      regulation of the epithelial- to-mesenchymal transition (EMT). The prognostic
      value of microRNA 200c in solid tumors remains controversial because of
      inconsistent data. Here, we report a meta-analysis of the association of microRNA
      200c expression and survival in patients with solid tumors. Pubmed was searched
      up to November 2013 for studies investigating microRNA 200c expression and
      overall survival (OS) in solid tumors. Hazard ratios (HRs) with 95% confidence
      intervals (CIs) for OS were extracted from each study. Pooled HR and CIs were
      calculated using the Mantel- Haenszel fixed-effects models. A total of five
      studies evaluating colorectal cancer, gastric cancer, ovarian cancer, pancreatic
      cancer and endometrial cancer were included in the analysis. Data were divided
      into tissue microRNA 200c expression group and serum microRNA 200c expression
      group. The combined HRs [95%CIs] estimated for OS were 0.62 [0.42-0.91] and 2.16
      [1.32-3.52] respectively. Low expression of microRNA 200c in tumor tissue and
      high expression of microRNA 200c in serum are associated with worse survival in
      solid tumors. Further study is needed to elucidate this contradiction. 

PMID- 24870779
TI  - Association between RASSF1A Ala133Ser polymorphism and cancer susceptibility: a
      meta-analysis involving 8,892 subjects.
AB  - BACKGROUND: Published studies on the association between the Ras Association
      Domain Family 1 isoform A (RASSF1A) Ala133Ser polymorphism and cancer
      susceptibility have yielded conflicting results. Thus, a meta- analysis was here
      performed to assess the possible association. MATERIALS AND METHODS: All eligible
      case-control studies published up to November 2013 on the association between
      RASSF1A Ala133Ser polymorphism and cancer susceptibility were identified by
      searching PubMed, Web of Science, Science Direct and hand search. Bothfixed-
      effect and random-effect models were used to calculate pooled odds ratios (ORs)
      with 95% confidence intervals (CIs) by using the Comprehensive Meta-Analysis
      software version 2.2. RESULTS: A total of 10 studies including 4,572 cancer cases
      and 4,320 controls were included in the meta-analysis. Overall, significantly
      increased cancer risk was associated with the variant Ser133 when all studies
      were pooled (Ser vs Ala: OR=1.51, 95% CI=1.08- 2.12, Pheterogeneity<=0.001;
      Ser/Ser+Ala/Ser vs Ala/Ala: OR=1.55, 95% CI=1.08-2.22, Pheterogeneity <= 0.001).
      Moreover, in subgroup analyses by cancer types, a significant association between
      RASSF1A Ala133Ser polymorphism and lung cancer risk was found (Ser vs Ala:
      OR=2.27, 95% CI=1.29-4.02, Pheterogeneity=0.61; Ser/Ser+Ala/ Ser vs Ala/Ala:
      OR=2.42, 95% CI=1.33-4.42, Pheterogeneity=0.75). In addition, in subgroup
      analyses by ethnicity, it was found that the RASSF1A Ala133Ser polymorphism was
      associated with overall cancer risk in Asians (Ser vs Ala: OR=1.37, 95% CI=1.06
      1.77, Pheterogeneity=0.06) and Caucasians (Ser/Ser+Ala/Ser vs Ala/Ala: OR=2.21,
      95% CI=1.01-4.82, Pheterogeneity<=0.001). CONCLUSIONS: This meta-analysis
      suggests, for the first time, that RASSF1A Ala133Ser polymorphism may contribute
      to cancer susceptibility, especially for lung cancer. Besides, additional well
      designed studies with larger sample size focusing on different ethnicities and
      cancer types are needed to confirm these findings.

PMID- 24870780
TI  - Knowledge, attitudes and beliefs about cervical cancer and human papilloma virus
      vaccination with related factors in Turkish university students.
AB  - BACKGROUND: This study aimed to determine knowledge, attitudes and believes about
      cervical cancer and human papilloma virus (HPV) vaccination with related factors
      in Turkish university students. MATERIALS AND METHODS: This descriptive and cross
      sectional study was conducted between June-July 2013 in Hitit University located
      in Corum, a rural area to the East of Ankara. The population consisted of 550
      university students who were training in first and last year from Faculties of
      Economics, Theology and Health. We reached 463 volunteer students without
      selection. The study of data was collected with a 44 item questionaire covering
      socio-demographic features, knowledge, attitudes and beliefs about cervical
      cancer, HPV and vaccination. Also for this study ethic committee report was taken
      from Bozok University. Data were evaluated with the SPSS 17.0 programme using the
      Ki kare test with P<0.05 accepted as statistically significant. RESULTS: It was
      seen that there was a statistically significant variation between classrooms and
      departments of students with knowledge about cervical cancer and human papilloma
      virus and vaccine (p<0.001; p<0.01; p<0.05). Also we found low attitudes to
      thinking about taking HPV vaccination of girls and their children in the future.
      CONCLUSIONS: In light of the study findings; it was concluded that knowledge
      levels, beliefs and attitudes of the university students about cervical cancer,
      HPV infection and HPV vaccination were low.

PMID- 24870781
TI  - Roles of E-cadherin (CDH1) genetic variations in cancer risk: a meta-analysis.
AB  - E-Cadherin (CDH1) genetic variations may be involved in invasion and metastasis
      of various cancers by altering gene transcriptional activity of epithelial cells.
      However, published studies on the association of CDH1 gene polymorphisms and
      cancer risk remain contradictory, owing to differences in living habits and
      genetic backgrounds. To derive a more better and comprehensive conclusion, the
      present meta-analysis was performed including 57 eligible studies of the
      association between polymorphisms of CDH1 gene promoter -160 C>A, -347 G>GA and
      3'-UTR +54 C>T and cancer risk. Results showed that these three polymorphisms of
      CDH1 were significantly associated with cancer risk. For -160 C>A polymorphism, 
      160A allele carriers (CA and CA+AA) had an increased risk of cancer compared with
      the homozygotes (CC), and the similar result was discovered for the -160A allele
      in the overall analyses. In the subgroup analyses, obvious elevated risk was
      found with -160A allele carriers (AA, CA, CA+AA and A allele) for prostate
      cancer, while a decreased colorectal cancer risk was shown with the AA genotype.
      For the -347 G>GA polymorphism, the GAGA genotype was associated with increased
      cancer risk in the overall analysis with homozygous and recessive models. In
      addition, results of subgroup analysis indicated that the elevated risks were
      observed in colorectal cancer and Asian descendants. For +54 C>T polymorphism, a
      decreased risk of cancer was found in heterozygous, dominant and allele models.
      Moreover, +54T allele carriers (CT, CT+TT genotype and T allele) showed a
      potential protective factor in gastric cancer and Asian descendants. 

PMID- 24870782
TI  - Lack of efficacy of Tai Chi in improving quality of life in breast cancer
      survivors: a systematic review and meta-analysis.
AB  - BACKGROUND: It is controversial whether Tai Chi (TC) benefits breast cancer
      survivors (BCS) on quality of life (QoL). We therefore undertook a meta-analysis
      to assess this question. MATERIALS AND METHODS: A computerized search through
      electronic databases was performed to identify relevant randomized controlled
      trials (RCTs). The primary outcome was QoL, while secondary outcomes included
      body mass index (BMI), bone mineral density (BMD), and muscle strength. RESULTS:
      Five RCTs involving 407 patients were included in the meta-analysis. The pooled
      standardized mean differences were 0.10 (95% confidence interval (CI): -0.35
      0.54) for physical well- being, 0.03 (95%CI: -0.18-0.25) for social/family well
      being, 0.24 (95%CI: 0.02-0.45) for emotional well-being, 0.23 (95%CI: -0.03-0.49)
      for functional well-being, and 0.09 (95%CI: -0.19-0.36) for additional concerns.
      TC failed to improve BMI, BMD, and muscle strength. CONCLUSIONS: There is
      currently lack of sufficient evidence to support TC improving QoL and other
      important clinical endpoints.

PMID- 24870783
TI  - Cancer: scenario and relationship of different geographical areas of the globe
      with special reference to North East-India.
AB  - BACKGROUND: Cancer is becoming the most important public health burden around the
      globe. As per the GLOBOCAN 2008 estimates, about 12.7 million cancer cases and
      7.6 million cancer deaths were estimated to have occurred in 2008. The burden of
      cancer cases for India in the year 2020 is calculated to be 1,148,757 (male
      534,353; female 614,404) compared to 979,786 in 2010. The pattern of cancer
      incidence is varying among geographical regions, esophageal cancer for example
      being high in China, lung cancer in USA, and gallbladder cancer in Chile. The
      question remains why? Is it due to the diversity in genome pool, food habits,
      risk factor association and role of genetic susceptibility or some other factors
      associated with it? In India, the North East (NE)-India region is seeing a marked
      increase in cancer incidence and deaths, with a very different cancer incidence
      pattern compared to mainland India. The genome pool of the region is also quite
      distinct from the rest of India. Northeastern tribes are quite distinct from
      other groups; they are more closely related to East Asians than to other Indians.
      In this paper an attempt was made to see whether there is any similarity among
      the pattern of cancer incidence cases for different sites of NE-India region to
      South or East-Asia. MATERIALS AND METHODS: Principal Component Analysis (PCA),
      Hierarchical Cluster Analysis (HCA), Pearson Correlation coefficient test was
      assessed to evaluate the linkage of North-East India region to other regions. A p
      value <0.05 was considered as statistically significant. RESULTS: The results
      clearly shows that there are similarities in occurrence of cancer incidence
      patterns for various cancer sites of NE-India with South and East-Asian regions,
      which may lead to the conclusion that there might be a genetic linkage between
      these regions.

PMID- 24870784
TI  - Rice bran phytic acid induced apoptosis through regulation of Bcl-2/Bax and p53
      genes in HepG2 human hepatocellular carcinoma cells.
AB  - Phytic acid (PA) has been reported to have positive nutritional benefits and
      prevent cancer formation. This study investigated the anticancer activity of rice
      bran PA against hepatocellular carcinoma (HepG2) cells. Cytotoxicty of PA (0.5 to
      4mM) was examined by MTT and LDH assays after 24 and 48 h treatment. Apoptotic
      activity was evaluated by expression analysis of apoptosis-regulatory genes [i.e.
      p53, Bcl-2, Bax, Caspase-3 and -9] by reverse transcriptase-PCR and DNA
      fragmentation assay. The results showed antioxidant activity of PA in Fe3+
      reducing power assay (p <= 0.03). PA inhibited the growth of HepG2 cells in a
      concentration dependent manner (p <= 0.04). After 48h treatment, cell viability
      was recorded 84.7, 74.4, 65.6, 49.6, 36.0 and 23.8% in MTT assay and 92.6, 77.0%,
      66.8%, 51.2, 40.3 and 32.3% in LDH assay at concentrations of 1, 1.5, 2.0, 2.5,
      3.0, and 3.5mM, respectively. Hence, treatment of PA for 24h, recorded viability
      of cells 93.5, 88.6, 55.5, 34.6 and 24.4% in MTT assay and 94.2, 86.1%, 59.7%,
      42.3 and 31.6%, in LDH assay at concentrations of 1, 2.2, 3.0, 3.6 and 4.0mM,
      respectively. PA treated HepG2 cells showed up-regulation of p53, Bax, Caspase-3
      and -9, and down- regulation of Bcl-2 gene (p <= 0.01). At the IC50 (2.49 mM) of
      PA, the p53, Bax, Caspase-3 and-9 genes were up- regulated by 6.03, 7.37, 19.7
      and 14.5 fold respectively. Also, the fragmented genomic DNA in PA treated cells
      provided evidence of apoptosis. Our study confirmed the biological activity of PA
      and demonstrated growth inhibition and induction of apoptosis in HepG2 cells with
      modulation of the expression of apoptosis-regulatory genes.

PMID- 24870785
TI  - Endometrial curettage in abnormal uterine bleeding and efficacy of progestins for
      control in cases of hyperplasia.
AB  - BACKGROUND: Abnormal uterine bleeding (AUB) is the most important symptom of
      endometrial hyperplasia and endometrial curettage (EC) is the gold standard
      diagnostic procedure. We present the results of patients who underwent EC for AUB
      and the efficacy of progestin administration in those with endometrial
      hyperplasia. MATERIALS AND METHODS: A total of 415 female patients who presented
      to Duzce Public Hospital in 2011-2012 for AUB and who underwent EC were included.
      We determined the reasons for AUB, and females with hyperplasia were treated with
      10 mg/day medroxyprogesterone acetate for 14 days/month or 160 mg/day megestrol
      acetate continuously for 3 months. We evaluated the efficacy of progestins for
      periods of three and/or six cycles by repeating EC. A statistical analysis of
      specific endometrial causes according to age of presentation was conducted using
      the chi-square test. RESULTS: Among the 415 females (average age, 53.5 years)
      followed for 6 months, 186 had physiological changes (44.8%), 89 had simple
      hyperplasia (21.44%), 1 had atypical hyperplasia (0.2%), 6 had (1.44%) complex
      hyperplasia, 3 had (0.72%) atypical complex hyperplasia, and 5 had adenocarcinoma
      (1.2%). Regression rates were 72.7-100%, and the optimum results were observed
      after 6 months of hormonal therapy. CONCLUSIONS: The main cause of AUB was
      physiological change. Progestin therapy resulted in significant regression even
      in females with atypical hyperplasia.

PMID- 24870786
TI  - Overexpression of platelet-derived growth factor-D as a poor prognosticator in
      endometrial cancer.
AB  - BACKGROUND: Emerging evidence implicates the platelet-derived growth factor-D
      (PDGF-D) in many types of human solid tumors. We investigated whether PDGF-D
      plays an important role in endometrial cancer (EC) in relation to
      clinicopathologic phenotype, angiogenesis, and patient prognosis. MATERIALS AND
      METHODS: We analyzed PDGF-D protein expression by Western blotting in twenty
      seven human endometrial cancer tissues, and matched normal endometrial controls
      collected at the third Affiliated hospital of Sun Yat-sen University during 2012
      2013 (n=27). Immunohistochemical staining was performed using a human PDGF-D
      antibody on the endometrial cancer patients collected in the same facility during
      January 2001 and October 2013 (n=152). Patients were followed from the time of
      primary surgery in 2001-2013 until death or last follow-up. We correlated the
      PDGF-D expression levels with clinicopathologic parameters and prognosis in human
      endometrial cancer patients. RESULTS: Compared with matched normal endometrial
      cases, PDGF-D was up-regulated in endometrial cancer. Expression of PDGF-D
      protein, found in 78% of the cases, was associated with nonendometrioid
      histologic type (p=0.028), FIGO stage III/IV (p=0.039), >50% solid tumor growth
      (p=0.048), pelvic LN metastasis (p=0.035) and ER and PR negativity (p=0.04 and
      0.002). PDGF-D expression was also significantly associated with expression of
      VEGF-A (p=0.021). In multivariate analysis, PDGF-D expression proved to be an
      independent prognostic factor in addition to histologic grade and FIGO stage.
      Patients with high expression levels of PDGF-D had a significantly poorer overall
      survival rate compared with patients with no expression. CONCLUSIONS: PDGF-D
      expression is frequently up-regulated in endometrial cancer, and is associated
      with aggressive features and poor prognosis.

PMID- 24870787
TI  - Establishment of and comparison between orthotopic xenograft and subcutaneous
      xenograft models of gallbladder carcinoma.
AB  - BACKGROUND: Gallbladder carcinoma (GBC) is the most common carcinoma of the
      biliary system. Among its research models, orthotopic xenograft models, important
      research tools, have been rarely reported in the literature however. AIM: To
      explore establishment of an orthotopic xenograft model and to evaluate the
      advantage and disadvantage as compared with other models. MATERIALS AND METHODS:
      Subcutaneous xenograft and orthotopic xenograft models of gallbladder carcinoma
      in nude mice were established and compared with human gallbladder carcinomas.
      RESULTS: For the orthotopic xenograft model and clinical gallbladder carcinomas,
      the lymph node metastatic rates were 69.2% and 53.3% (p>0.05); ascites generation
      rates, 38.5% and 11.7%(p<0.05); liver invasive rates, 100% and 61.7%(p<0.05); and
      lymphatic vessel densities (LVD), 10.4 +/- 3.02 and 8.77 +/- 2.92 (p>0.05),
      respectively. In the subcutaneous xenograft model, no evidence of ascites
      generation, lymph node metastasis and liver metastasis were found, and its LVD
      was lower (4.56 +/- 1.53, p<0.05). CONCLUSIONS: Compared with the subcutaneous
      xenograft model, the orthotopic xenograft model better simulates clinical
      gallbladder carcinoma in terms of metastasis and invasion, which may be
      attributed to the difference in microenvironment and LVD.

PMID- 24870789
TI  - Is the tumor infiltrating natural killer cell (NK-TILs) count in infiltrating
      ductal carcinoma of breast prognostically significant?
AB  - PURPOSE: The aim of this study was to investigate the prognostic significance of
      the CD56+NK-TIL count in infiltrating ductal carcinoma (IDC) of breast. MATERIAL
      AND METHODS: Immunohistochemistry (IHC) was performed using antibodies specific
      for CD56 on formalin-fixed and paraffin-embedded tissue sections of 175
      infiltrating ductal carcinomas (IDC) of breast. Distribution of intratumoral and
      stromal CD56+NK-TILs was assessed semi-quantitatively. RESULTS: A low
      intratumoral CD56+count showed significant and inverse associations with tumor
      grade, stage, and lymph node status, whereas it had significant and direct
      association with response to treatment indicating good prognosis. These patients
      had better survival (chi2=4.80, p<0.05) and 0.52 fold lower death rate (HR=0.52,
      95% CI=0.28-0.93) as compared to patients with high CD56+ intratumoral count. The
      association of survival was insignificant with low CD56 stromal count as compared
      to high CD56 stromal count (chi2=1.60, p>0.05). CONCLUSION: To conclude, although
      NK-TIL count appeared as a significant predictor of prognosis, it alone may not
      be sufficient for predicting the outcome considering the fact that there exists a
      crosstalk between NK-TILs and the other immune infiltrating TILs.

PMID- 24870788
TI  - Factors affecting cervical cancer screening uptake by Hmong hilltribe women in
      Thailand.
AB  - BACKGROUND: Cervical cancer is relatively common in Thai women, but the
      proportion of females receiving Pap smear screening is still low. OBJECTIVE: The
      purpose of this cross-sectional study was to study factors related to cervical
      cancer screening uptake by Hmong hilltribe women in Lomkao District, Phetchabun
      Province. MATERIALS AND METHODS: Interview data were collected from 547 of these
      women aged 30-60 years living in the study area and analyzed using multiple
      logistic regression. RESULTS: The results showed that 64.9% of the study sample
      had received screening, and that 47.2% had attended due to a cervical screening
      campaign. The most common reason given for not receiving screening was lack of
      time (21.4%). The factors found to be positively associated with uptake (p value
      <0.05) were as follows: number of years of school attendance (OR=1.56, 95%CI:1.02
      2.38), animistic religious beliefs (OR=0.55, 95%CI:0.33-0.91), a previous
      pregnancy (OR=6.20, 95%CI:1.36-28.35), receipt of information about cervical
      cancer screening (OR=2.25, 95%CI:1.35-3.76), and perceived risk of developing
      cervical cancer (OR=1.83, 95%CI:1.25-2.67). CONCLUSIONS: To promote the uptake of
      cervical screening, Hmong hilltribe women need to know more about cervical cancer
      and cervical cancer screening, and access to screening services should be
      provided in conjunction with existing everyday services, such as family planning
      and routine blood pressure monitoring or diabetes services.

PMID- 24870790
TI  - Analysis of different activation statuses of human mammary epithelial cells from
      young and old groups.
AB  - Human mammary epithelial cells have different proliferative statuses and
      demonstrate a close relationship with age and cell proliferation. Research on
      this topic could help understand the occurrence, progression and prognosis of
      breast cancer. In this article, using significance analysis of a microarray
      algorithm, we analyzed gene expression profiles of human mammary epithelial cells
      of different proliferative statuses and different age groups. The results showed
      there were significant differences in gene expression in the same proliferation
      status between elderly and young groups. Three common differentially expressed
      genes were found to dynamically change with the proliferation status and to be
      closely related to tumorigenesis. We also found elderly group had less status
      related differential genes from actively proliferating status to intermediate
      status and more status- related differential genes from intermediate status than
      the young group. Finally, functional enrichment analyses allowed evaluation of
      the detailed roles of these differentially-expressed genes in tumor progression. 

PMID- 24870792
TI  - HPV detection and genotyping in vulvar squamous cell carcinoma in northern
      Thailand.
AB  - BACKGROUND: The study was aimed to evaluate the prevalence and genotype
      distribution of HPV infection in vulvar squamous cell carcinoma (SCC) in northern
      Thailand and the clinicopathological difference with regard to HPV infection
      status. MATERIALS AND METHODS: Formalin-fixed paraffin-embedded tissue samples of
      vulvar SCC diagnosed between January 2006 and December 2012 were collected. HPV
      infection was detected by nested polymerase chain reaction (PCR) with primers
      MY09/11 and GP5+/6+. HPV genotyping was performed using the Linear Array
      Genotyping Test, followed by type-specific PCR targeting the E6/E7 region of
      HPV16/18/52 if the Linear Array test was negative. The histologic slides of
      vulvar lesions and the medical records were reviewed. RESULTS: There were 47
      cases of vulvar SCC included in the study (mean patient age 57.9 +/- 13.2 years).
      HPV infection was detected in 29 cases (62%), all of which had single HPV
      infections. HPV16 accounted for 23 (49%). The patients with HPV-positive SCC had
      a significantly younger mean age than those with HPV-negative tumors (52.7 years
      vs 66.2 years, p<0.001). There was no significant difference in tumor stage
      distribution with regard to the status of HPV infection. The presence of vulvar
      intraepithelial neoplasia (VIN) of usual type (basaloid or warty) was
      significantly more frequent in HPV-positive cases compared with HPV-negative
      cases (62% vs 6%, p<0.001), whereas differentiated-type VIN was more common in
      HPV-negative cases (24% vs 0%, p=0.019). CONCLUSIONS: HPV infection was detected
      in 62% of vulvar SCC in northern Thailand. HPV16 was the predominant genotype
      similar to the data reported from other regions. HPV-positive SCC occurred in
      younger patients compared with HPV-negative SCC, and was associated with usual
      type VIN. Vaccination against HPV16/18 may potentially prevent almost one half of
      vulvar SCC in northern Thailand.

PMID- 24870791
TI  - MiR-133b acts as a tumor suppressor and negatively regulates TBPL1 in colorectal
      cancer cells.
AB  - INTRODUCTION: MicroRNAs have emerged as post-transcriptional regulators that are
      critically involved in tumorigenesis. This study was designed to explore the
      effect of miRNA 133b on the proliferation and expression of TBPL1 in colon cancer
      cells. METHODS: Human colon cancer SW-620 cells and human colon adenocarcinoma HT
      29 cells were cultured. MiRNA 133b mimcs, miRNA 133b inhibitors, siRNA for TBPL1
      and scrambled control were synthesized and transfected into cells. MiR-133b
      levels in cells and CRC tumor tissue was measured by real-time PCR. TBPL1 mRNA
      was detected by RT-PCR. Cell proliferation was studied with MTT assay. Western
      blotting was applied to detect TBPL1 protein levels. Luciferase assays were
      conducted using a pGL3-promoter vector cloned with full length of 3'UTR of human
      TBPL1 or 3'UTR with mutant sequence of miR-133b target site in order to confirm
      if the putative binding site is responsible for the negative regulation of TBPL1
      by miR- 133b. RESULTS: Real time PCR results showed that miRNA 133b was lower in
      CRC tissue than that in adjacent tissue. After miR-133b transfection, its level
      was elevated till 48h, accompanied by lower proliferation in both SW-620 and HT
      29 cells. According to that listed in http://www.targetscan.org, the 3'-UTR of
      TBPL1 mRNA (NM_004865) contains one putative binding site of miR-133b. This site
      was confirmed to be responsible for the negative regulation by miR-133b with
      luciferase assay. Further, Western blotting and immunohistochemistry both
      indicated a higher TBPL1 protein expression level in CRC tissue. Finally, a siRNA
      for TBPL1 transfection obviously slowed down the cell proliferation in both SW
      620 and HT-29 cells. CONCLUSION: MiR-133b might act as a tumor suppressor and
      negatively regulate TBPL1 in CRC.

PMID- 24870793
TI  - Significance of the plasma lipid profile in cases of carcinoma of cervix: a
      tertiary hospital based study.
AB  - AIMS: To study alterations of plasma lipid profiles in carcinoma cervix and to
      assess significance compared with controls in different histological grades and
      stages. MATERIALS AND METHODS: Totals of 99 histopathologically diagnosed cases
      and 35 controls from a tertiary hospital situated in the southern part of India
      which caters the rural and semi-urban populations were considered for the study.
      Fasting blood samples were taken to analyze total cholesterol (TC), triglycerides
      (TG), high density lipoprotein cholesterol (HDL-C) and low density lipoproteins
      cholesterol (LDL-C), for comparison of cases, grouped according to histological
      grades and stages, and controls. One way ANOVA was used for multiple group
      comparisons and the Student's t test (unpaired) for group wise comparisons. For
      all tests a 'p' value of 0.05 or less was considered as significant. RESULTS: Out
      of 99 cases, most (n-39) were seen in the 40-49 year age group followed by 60-69
      years (n-22). Serum TG significantly differed between cases and controls but
      without any relation to differentiation grade. The lipid profile parameters in
      various grades of cervical cancer were not statistically significant.
      Statistically significant increase of TC and LDL-C values was observed with
      increase in stage of the disease. CONCLUSIONS: The study showed TG is elevated in
      cervical cancer, and that TC and LDL-C are proportional to the spread of cancer
      as it increases from stage I to stage IV. An in-depth study of molecular changes
      in lipid metabolism in cervical cancer patients, enzymes/ genes responsible and
      alterations in LDL receptors is necessary to provide information to decide
      whether the lipid profile has any diagnostic/prognostic role in cervical cancer.

PMID- 24870794
TI  - Retrograde analysis of clinical characteristics of bone metastasis in 1,031 cases
      of preliminarily diagnosed nasopharyngeal carcinoma.
AB  - PURPOSE: To explore the clinical characteristics of bone metastasis (BM) in a
      large sample of preliminarily diagnosed nasopharyngeal carcinomas (NPCs).
      METHODS: The sample consisted of 1,031 patients diagnosed with NPC at first
      visitg clinics between October 1989 and June 2012. Several parameters including
      metastasis locus, T/N staging, diagnosis, therapy and prognosis of BM were
      analyzed retrospectively. RESULTS: In 70 patients who had been preliminarily
      diagnosed with BM, the incidence of BM in N0, N1, N2 and N3 stage was 5.7%,
      17.2%, 50.2%, and 25.7%, respectively, while the incidence in T0, T1, T2 and T3
      stage was 0%, 23.8%, 47.6% and 28.6% respectively. BM occurred in most common in
      vertebral column, rib, sternum, ilium and femur. Positive rate of Epstein-Barr
      virus antibody was 77.6%. The median survival time was 12 months. CONCLUSION: The
      incidence of BM in NPC preliminarily diagnosed is about 7% and it is related to N
      classification but not T classification.

PMID- 24870795
TI  - Interactions between filamin A and MMP-9 regulate proliferation and invasion in
      renal cell carcinoma.
AB  - This study aimed to analyze the expression, clinical significance of filamin A
      (FLNA) in renal cell carcinoma (RCC) and biological effects in a cell line by
      regulating FLNA expression. Immunohistochemistry and Western blotting were used
      to analyze FLNA protein expression in 70 cases of RCC and normal tissues to study
      the relationship with clinical factors. FLNA lentiviral and empty vectors were
      transfected into RCC to study the influence of up-regulated expression of FLNA.
      FLNA siRNA was transiently transfected into ACHN kidney carcinoma cells by a
      liposome-mediated method and protein was detected by Western blotting. The level
      of expression was found to be significantly lower in RCC than normal tissues
      (p<0.05). No correlation was noted with gender, age, tumor size or pathological
      types (p>0.05), but links with lymph node metastasis, clinic stage and
      histological grade were noted (p<0.05). Loss of FLNA expression correlated
      significantly with poor overall survival time by Kaplan-Meier analysis (p<0.05).
      Results for biological function showed that ACHN cells transfected with FLNA had
      a lower survival fraction, significant decrease in migration and invasion, higher
      cell apoptosis, higher percentage of the G0/G1 phases, and lower MMP-9 protein
      expression compared with ACHN cells untransfected with FLNA (p<0.05). However,
      renal 786-0 cells transfected with FLNA siRNA had a higher survival fraction,
      significant increase in migration and invasion, and higher MMP-9 protein
      expression compared (p<0.05). In conclusion, FLNA expression was decreased in RCC
      and correlated significantly with lymph node metastasis, clinic stage,
      histological grade and poor overall survival, suggesting that FLNA may play
      important roles as a a tumor suppressor in RCC by promoting degradation of MMP-9.

PMID- 24870796
TI  - BMI1 and TWIST1 downregulated mRNA expression in basal cell carcinoma.
AB  - BACKGROUND: BMI1, TWIST1 and SNAI2/SLUG have been implicated in aggressive
      behavior of squamous cell carcinoma (SCC) and melanoma and BMI1 expression could
      identify subtypes of Merkel cell carcinoma (MCC). However, BMI1, TWIST1 and SNAI2
      expression levels in basal cell carcinomas (BCCs) have not been elucidated. We
      hypothesized BCC could be a good model system to decipher mechanisms which
      inhibit processes that drive tumor metastasis. The aim of this study was to
      examine the mRNA expression level of BMI1, TWIST1, and SNAI2 in BCCs. MATERIALS
      AND METHODS: Thirty-five fresh non-metastatic BCC tissue samples and seven fresh
      normal skin tissue samples were evaluated by real-time RT-PCR. RESULTS: BMI1 and
      TWIST1 demonstrated marked down-regulation (p<0.00l, p=0.00l respectively), but
      SNAI2 showed no significant change (p=0.12). CONCLUSIONS: Previous literature has
      clearly demonstrated a positive association between BMI1 and TWIST1 expression
      and metastatic BCC, aggressive SCC and melanoma. Here, we demonstrated a negative
      association between BMI1 and TWIST1 mRNA expression level and BCC.

PMID- 24870797
TI  - Prognostic value of hematologic parameters in patients with metastatic renal cell
      carcinoma using tyrosine kinase inhibitors.
AB  - BACKGROUND: The prognostic significance of the neutrophil-to-lymphocyte ratio for
      progression free survival in patients with metastatic renal cell carcinoma is
      unclear. MATERIALS AND METHODS: We retrospectively reviewed 45 patients diagnosed
      with metastatic RCC previously treated with tyrosine kinase inhibitors from two
      centers, Akdeniz University Hospital and Afyon Kocatepe University. The
      prognostic value of the pretreatment neutrophil- tolymphocyte ratio, and other
      clinical and laboratory parameters were assessed by univariate and multivariate
      analysis. RESULTS: Median progression free survival (PFS) was 13.9 months [95% CI
      for HR (6.88-20.91)] and overall survival figure of 16.6 months [95% CI for HR
      (7.23-26.03)] Univariate analysis revealed that PFS was significantly affected by
      hemoglobin level [p=0.013 (95% CI for HR (0.71-0.96))], eosinophil count [p=0.031
      (95% CI for HR (0.20-0.92))], ratio of neutrophil lymphocytes (NLR) [p=0.007 (95%
      CI for HR (1.47-11.74))] and calcium level [p=0.006 (95% CI for HR (0.15-0.73))].
      However, only NLR [p=0.031 (95% CI for HR (1.15- 18.1))] and calcium levels
      [p=0.018 (95% CI for HR (0.20-18.1))] retained significance with multivariate
      analysis. Median PFS was 23.9 vs 8.6 months in patients with NLR <= 2 vs NLR >2
      (Log rank; p= 0.040). CONCLUSIONS: This study showed that increased pretreatment
      NLR is an independent prognostic factor for patients with metastatic RCC using
      tyrosine kinase inhibitors.

PMID- 24870798
TI  - CYP3A4 expression in breast cancer and its association with risk factors in
      Mexican women.
AB  - BACKGROUND: In Mexico, breast cancer (BCa) is the leading type of cancer in
      women. Cytochrome P450 (CYP450) is a superfamily of major oxidative enzymes that
      metabolize carcinogens and many antineoplastic drugs. In addition, these enzymes
      have influence on tumor development and tumor response to therapy. In this
      report, we analyzed the protein expression in patients with BCa and in healthy
      women. Links with some clinic-pathological characteristic were also assessed.
      MATERIALS AND METHODS: Immunohistochemical analyses were conducted on 48 sets of
      human breast tumors and normal breast tissues enrolled in Hospital Militar de
      Especialidades de la Mujer y Neonatologia and Hospital Central Militar,
      respectively, during the time period from 2010 to 2011. Informed consent was
      obtained from all participants. Statistical analysis was performed using chi2 or
      Fisher exact tests to estimate associations and the Mann Whitney U test for
      comparison of group means. RESULTS: We found a significant CYP3A4 overexpression
      in BCa stroma and gland regions in comparison with healthy tissue. A significant
      association between protein expression with smoking, alcoholism and hormonal
      contraceptives use was also observed. Additionally, we observed estrogen receptor
      (ER) and progesterone receptor (PR) positive association in BCa. CONCLUSIONS: We
      suggest that CYP3A4 expression promotes BCa development and can be used in the
      prediction of tumor response to different treatments. One therapeutic approach
      may thus be to block CYP3A4 function.

PMID- 24870799
TI  - Nitric oxide synthase 3 gene variants and colorectal cancer: a meta-analysis.
AB  - BACKGROUND: Colorectal cancer (CRC) is the worldwide disease which causes
      enormous losses every year. Recent studies suggested that environmental and gene
      factors might be the etiologies in increasing the risk of morbidity. Nitric oxide
      synthase 3 (NOS3) gene polymorphisms are said to be associated with CRC risk but
      the conclusion is still controversial. MATERIALS AND METHODS: Pubmed and HuGENet
      databases up to December 2013 were used in this meta-analysis. Three different
      certain genotypic models were applied, namely dominant (AA+AC versus CC),
      recessive (AA versus AC+CC), per-allele analysis (A vs C). In addition,
      information on tumor sites and pathologic stages was collected. The strength of
      associations was assessed through combining odds ratio (OR) and 95% confidence
      interval (CI). RESULTS: Finally, five and three studies about the rs1799983 and
      rs2070744 were covered in the analysis with 2,745 cases and 2,478 controls. Three
      models were applied, but no significant association was found for NOS3
      G894T/rs1799983 (dominant: OR=0.999, 95%CI=0.797-1.253, I2=63.8%; recessive:
      OR=0.924, 95%CI=0.589-1.450, I2=59.3%; allele analysis: OR=0.979, 95%CI=0.788
      1.216, I2=74.9%) and T-786C/rs2070744 (dominant: OR=1.138, 95%CI=0.846-1.530,
      I2=67.9%; recessive: OR=0.956, 95%CI=0.708-1.291, I2=0.0%; allele analysis:
      OR=1.110, 95%CI=0.865-1.425, I2=69.4%). The same results were also obtained for
      tumor sites and pathologic stage subgroups. After further analyzing the NOS3
      gene, rs1799983 as the tag- and functional SNP was presented. CONCLUSIONS: On the
      basis of this meta-analysis and the characteristics of the NOS3 gene, we
      suggested rs1799983 might be a key locus associated with CRC risk. Further
      prospective studies were needed to make more comprehensive explanation of the
      associations.

PMID- 24870800
TI  - A functional SNP in the MDM2 promoter mediates E2F1 affinity to modulate cyclin
      D1 expression in tumor cell proliferation.
AB  - BACKGROUND: The MDM2 oncogene, a negative regulator of p53, has a functional
      polymorphism in the promoter region (SNP309) that is associated with multiple
      kinds of cancers including non-melanoma skin cancer. SNP309 has been shown to
      associate with accelerated tumor formation by increasing the affinity of the
      transcriptional activator Sp1. It remains unknown whether there are other factors
      involved in the regulation of MDM2 transcription through a trans-regulatory
      mechanism. METHODS: In this study, SNP309 was verified to be associated with
      overexpression of MDM2 in tumor cells. Bioinformatics predicts that the T to G
      substitution at SNP309 generates a stronger E2F1 binding site, which was
      confirmed by ChIP and luciferase assays. RESULTS: E2F1 knockdown downregulates
      the expression of MDM2, which confirms that E2F1 is a functional upstream
      regulator. Furthermore, tumor cells with the GG genotype exhibited a higher
      proliferation rate than TT, correlating with cyclin D1 expression. E2F1 depletion
      significantly inhibits the proliferation capacity and downregulates cyclin D1
      expression, especially in GG genotype skin fibroblasts. Notably, E2F1 siRNA
      effects could be rescued by cyclin D1 overexpression. CONCLUSION: Taken together,
      a novel modulator E2F1 was identified as regulating MDM2 expression dependent on
      SNP309 and further mediates cyclin D1 expression and tumor cell proliferation.
      E2F1 might act as an important factor for SNP309 serving as a rate-limiting event
      in carcinogenesis.

PMID- 24870801
TI  - Impact of an enhanced recovery program on colorectal cancer surgery.
AB  - Surgical outcomes of colorectal cancer treatment depend not only on good surgery
      and tumor biology but also on an optimal perioperative care. The enhanced
      recovery program (ERP) - a multidisciplinary and multimodal approach, or so
      called 'fast-track surgery' - has been designed to minimize perioperative and
      intraoperative stress responses, and to support the recovery of organ function
      aiming to help patients getting better sooner after surgery. Compared with
      conventional postoperative care, the enhanced recovery program results in quicker
      patient recovery, shorter length of hospital stay, faster recovery of
      gastrointestinal function, and a lower incidence of postoperative complications.
      Although not firmly established as yet, the enhanced recovery program after
      surgery could be of oncological benefit in colorectal cancer patients because it
      can enhance recovery, maintain integrity of the postoperative immune system,
      increase feasibility of postoperative chemotherapy, and shorten the time interval
      from surgery to chemotherapy. This commentary summarizes short-term outcomes and
      potential long-term benefits of enhanced recovery programs in the treatment of
      colorectal cancer. 

PMID- 24870802
TI  - Anatomy of beta-strands at protein-protein interfaces.
AB  - The development of inhibitors for protein-protein interactions frequently
      involves the mimicry of secondary structure motifs. While helical protein-protein
      interactions have been heavily targeted, a similar level of success for the
      inhibition of beta-strand and beta-sheet rich interfaces has been elusive. We
      describe an assessment of the full range of beta-strand interfaces whose high
      resolution structures are available in the Protein Data Bank. This analysis
      identifies complexes where a beta-stand or beta-sheet contributes significantly
      to binding. The results highlight the molecular recognition complexity in strand
      mediated interactions relative to helical interfaces and offer guidelines for the
      construction of beta-strand and beta-sheet mimics as ligands for protein
      receptors. The online data set will potentially serve as an entry-point to new
      classes of protein-protein interaction inhibitors. 

PMID- 24870804
TI  - CARP is a potential tumor suppressor in gastric carcinoma and a single-nucleotide
      polymorphism in CARP gene might increase the risk of gastric carcinoma.
AB  - BACKGROUND: The caspase-associated recruitment domain-containing protein (CARP)
      is expressed in almost all tissues. Recently, the tumor-suppressive function of
      CARP was discovered and attracted increasing attention. This study aimed to
      investigate the role of CARP in the carcinogenesis of human gastric carcinoma.
      METHODOLOGY/PRINCIPAL FINDINGS: Compared with normal gastric tissue, the
      downregulation of CARP expression was observed in gastric carcinoma tissue by
      cDNA array and tissue microarray assay. In vitro, the gastric carcinoma cell line
      (BGC-823) was stably transfected with pcDNA3.1B-CARP or plus CARP siRNA, and we
      used MTT, flow cytometry, cell migration on type I collagen, cell-matrix adhesion
      assay and western blot analysis to investigate the potential anti-tumor effects
      of CARP. The data showed that overexpressing CARP suppressed the malignancy of
      gastric carcinoma BGC-823 cell line, including significant increases in
      apoptosis, as well as obvious decreases in cell proliferation, migration,
      adhesion ability, and tumor growth. The tumor-suppressive effects of CARP were
      almost restored by siRNA-directed CARP silence. In addition, overexpression of
      CARP induced G1 arrest, decreased the expressions of cyclin E and CDK2, and
      increased the expressions of p27, p53 and p21. In vivo, the tumor-suppressive
      effect of CARP was also verified. A single-nucleotide polymorphism (SNP) genotype
      of CARP (rs2297882) was located in the Kozak sequence of the CARP gene. The
      reporter gene assay showed that rs2297882 TT caused an obvious downregulation of
      activity of CARP gene promoter in BGC-823 cells. Furthermore, the association
      between rs2297882 and human gastric carcinoma susceptibility was analyzed in 352
      cases and 889 controls. It displayed that the TT genotype of rs2297882 in the
      CARP gene was associated with an increased risk of gastric carcinoma.
      CONCLUSIONS/SIGNIFICANCE: CARP is a potential tumor suppressor of gastric
      carcinoma and the rs2297882 C>T phenotype of CARP may serve as a predictor of
      gastric carcinoma.

PMID- 24870805
TI  - Loss of gq/11 genes does not abolish melanopsin phototransduction.
AB  - In mammals, a subset of retinal ganglion cells (RGCs) expresses the photopigment
      melanopsin, which renders them intrinsically photosensitive (ipRGCs). These
      ipRGCs mediate various non-image-forming visual functions such as circadian
      photoentrainment and the pupillary light reflex (PLR). Melanopsin
      phototransduction begins with activation of a heterotrimeric G protein of unknown
      identity. Several studies of melanopsin phototransduction have implicated a G
      protein of the Gq/11 family, which consists of Gna11, Gna14, Gnaq and Gna15, in
      melanopsin-evoked depolarization. However, the exact identity of the Gq/11 gene
      involved in this process has remained elusive. Additionally, whether Gq/11 G
      proteins are necessary for melanopsin phototransduction in vivo has not yet been
      examined. We show here that the majority of ipRGCs express both Gna11 and Gna14,
      but neither Gnaq nor Gna15. Animals lacking the melanopsin protein have well
      characterized deficits in the PLR and circadian behaviors, and we therefore
      examined these non-imaging forming visual functions in a variety of single and
      double mutants for Gq/11 family members. All Gq/11 mutant animals exhibited PLR
      and circadian behaviors indistinguishable from WT. In addition, we show
      persistence of ipRGC light-evoked responses in Gna11-/-; Gna14-/- retinas using
      multielectrode array recordings. These results demonstrate that Gq, G11, G14, or
      G15 alone or in combination are not necessary for melanopsin-based
      phototransduction, and suggest that ipRGCs may be able to utilize a Gq/11
      independent phototransduction cascade in vivo. 

PMID- 24870808
TI  - Beyond policy analysis: the raw politics behind opposition to healthy public
      policy.
AB  - Despite evidence that public policy that equitably distributes the
      prerequisites/social determinants of health (PrH/SDH) is a worthy goal, progress
      in achieving such healthy public policy (HPP) has been uneven. This has
      especially been the case in nations where the business sector dominates the
      making of public policy. In response, various models of the policy process have
      been developed to create what Kickbusch calls a health political science to
      correct this situation. In this article I examine an aspect of health political
      science that is frequently neglected: the raw politics of power and influence.
      Using Canada as an example, I argue that aspects of HPP related to the
      distribution of key PrH/SDH are embedded within issues of power, influence, and
      competing interests such that key sectors of society oppose and are successful in
      blocking such HPP. By identifying these opponents and understanding why and how
      they block HPP, these barriers can be surmounted. These efforts to identify
      opponents of HPP that provide an equitable distribution of the PrH/SDH will be
      especially necessary where a nation's political economy is dominated by the
      business and corporate sector.

PMID- 24870809
TI  - The use of a Mitsunobu reagent for the formation of heterocycles: a simple method
      for the preparation of 3-alkyl-5-aryl-1,3,4-oxadiazol-2(3H)-ones from carboxylic
      acids.
AB  - The reaction of carboxylic acids with Mitsunobu reagents, prepared by the
      reaction of triphenylphosphine with dialkyl azodicarboxylates, followed by
      heating at 180-190  degrees C under solvent-free conditions, afforded 3-alkyl-5
      aryl-1,3,4-oxadiazol-2(3H)-ones. This facile and convenient method readily
      provides the 1,3,4-oxadiazolone ring systems in good yields using a one-pot
      protocol starting from the corresponding carboxylic acids. It was also
      demonstrated that the presence of a catalytic base facilitates the final ring
      closure forming the 1,3,4-oxadiazol-2(3H)-one. 

PMID- 24870806
TI  - Enhanced humoral immunity in mice lacking CB1 and CB2 receptors (Cnr1-/-/Cnr2-/-
      mice) is not due to increased splenic noradrenergic neuronal activity.
AB  - Peripheral sympathetic noradrenergic neurons originating in the celiac mesenteric
      plexus have axons that terminate in close proximity to antibody-producing B cells
      in the spleen. Norepinephrine (NE) released from these neurons is reported to
      augment antibody production in response to an immune challenge via an action at
      the beta2-adrenergic receptor (beta2AR). Cannabinoids are immunosuppressive, and
      mice lacking CB1 and CB2 receptors (Cnr1(-/-)/Cnr2(-/-) mice) have augmented cell
      mediated immune responses. The purpose of this study was to determine if Cnr1(-/
      )/Cnr2(-/-) mice also exhibit enhanced humoral immunity and if that is associated
      with corresponding changes in noradrenergic neurons terminating in the spleen.
      The results reveal that IgM and IgG are enhanced in Cnr1(-/-)/Cnr2(-/-) mice as
      compared to WT both in immunologically naive and lipopolysaccharide (LPS)-treated
      mice. While the elevated antibody production was correlated with increased
      expression of beta2AR on splenic B cells and increased splenic capsule NE
      concentrations, the activity of noradrenergic neurons was suppressed in spleens
      from Cnr1(-/-)/Cnr2(-/-) mice as compared with WT controls. Together, these
      results suggest that Cnr1(-/-)/Cnr2(-/-) mice exhibit enhanced NE vesicular
      storage in axon terminals in these neurons, which might limit the NE available to
      bind beta2AR on target cells, such as B cells. The results also demonstrate that
      enhanced antibody responses in the absence of CB1 and CB2 receptors are not due
      to increased sympathetic noradrenergic neuronal activity in the spleen.

PMID- 24870811
TI  - Whole cell cryo-electron tomography suggests mitochondria divide by budding.
AB  - Eukaryotes rely on mitochondrial division to guarantee that each new generation
      of cells acquires an adequate number of mitochondria. Mitochondrial division has
      long been thought to occur by binary fission and, more recently, evidence has
      supported the idea that binary fission is mediated by dynamin-related protein
      (Drp1) and the endoplasmic reticulum. However, studies to date have depended on
      fluorescence microscopy and conventional electron microscopy. Here, we utilize
      whole cell cryo-electron tomography to visualize mitochondrial division in frozen
      hydrated intact HeLa cells. We observe a large number of relatively small
      mitochondria protruding from and connected to large mitochondria or mitochondrial
      networks. Therefore, this study provides evidence that mitochondria divide by
      budding. 

PMID- 24870810
TI  - Identification of glutathione S-transferase genes responding to pathogen
      infestation in Populus tomentosa.
AB  - Stem blister canker, caused by Botryosphaeria dothidea, is becoming the most
      serious disease of poplar in China. The molecular basis of the poplar in response
      to stem blister canker is not well understood. To reveal the global
      transcriptional changes of poplar to infection by B. dothidea, Solexa paired-end
      sequencing of complementary DNAs (cDNAs) from control (NB) and pathogen-treated
      samples (WB) was performed, resulting in a total of 339,283 transcripts and
      183,881 unigenes. A total of 206,586 transcripts were differentially expressed in
      response to pathogen stress (false discovery rate <=0.05 and an absolute value of
      log2Ratio (NB/WB) >=1). In enrichment analysis, energy metabolism and redox
      reaction-related macromolecules were accumulated significantly in Gene Ontology
      and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analyses, indicating
      components of dynamic defense against the fungus. A total of 852 transcripts (575
      upregulated and 277 downregulated transcripts) potentially involved in plant
      pathogen interaction were also differentially regulated, including genes encoding
      proteins linked to signal transduction (putative leucine-rich repeat (LRR)
      protein kinases and calcium-binding proteins), defense (pathogenesis-related
      protein 1), and cofactors (jasmonate-ZIM-domain-containing proteins and heat
      shock proteins). Moreover, transcripts encoding glutathione S-transferase (GST)
      were accumulated to high levels, revealing key genes and proteins potentially
      related to pathogen resistance. Poplar RNA sequence data were validated by
      quantitative real-time PCR (RT-qPCR), which revealed a highly reliability of the
      transcriptomic profiling data. 

PMID- 24870812
TI  - Arsenic speciation in newberyite (MgHPO(4).3H(2)O) determined by synchrotron X
      ray absorption and electron paramagnetic resonance spectroscopies: implications
      for the fate of arsenic in green fertilizers.
AB  - Newberyite (MgHPO4.3H2O), a biomineral and common constituent in guano deposits,
      is an important decomposition product of struvite that is an increasingly popular
      green fertilizer recovered from wastewaters. Two samples of newberyite containing
      1099 and 25 ppm As have been obtained at pH = 6.4, by using Na2HAsO4.7H2O and
      NaAsO2 as the dopant, respectively (i.e., Synthesis 1 and Synthesis 2).
      Synchrotron arsenic K-edge X-ray absorption spectroscopic data of newberyite from
      Synthesis 1 show that As(5+) is dominant and has a local environment typical of
      the arsenate species. Single-crystal electron paramagnetic resonance (EPR)
      spectra of gamma-ray-irradiated newberyite from Synthesis 1 contain two arsenic
      associated oxyradicals: [AsO3](2-) and [AsO2](2-) derived from As(5+) and As(3+),
      respectively, at the P site. Quantitative analyses of powder EPR spectra allow
      determinations of the As(5+) and As(3+) contents in newberyite from Synthesis 1
      and Synthesis 2. Elevated concentrations of arsenic also occur in natural
      newberyite transformed from struvite in guano deposits and record the
      accumulation of this metalloid in the food chain. Therefore, newberyite, which
      sequesters As during crystallization and retains this metalloid during the
      transformation from struvite, can attenuate arsenic contamination from green
      fertilizers in moderately acidic soils. Also, the capacity for accommodating both
      As(5+) and As(3+) in the crystal lattice coupled with simple chemistry and easy
      crystallization at ambient conditions makes newberyite an attractive material for
      remediation of arsenic contamination in aqueous environments. 

PMID- 24870813
TI  - Polymorphisms for ghrelin with consequences on satiety and metabolic alterations.
AB  - PURPOSE OF REVIEW: To understand the current trend of ghrelin genetic variations
      on the control of satiety, eating behaviours, obesity, and metabolic alterations,
      and its development over the last 18 months. RECENT FINDINGS: Several
      polymorphisms of the ghrelin gene, its receptor gene and ghrelin's acylating
      enzyme, ghrelin O-acyl transferase, have been identified and studied over the
      last decade in relation to control of satiety, obesity, eating behaviours,
      metabolic syndrome, glucose homeostasis, and type 2 diabetes. However, the
      effects described are either small or nonsignificant and often subjected to
      contradictory conclusions between studies. In the last 18 months, several of
      these areas of investigations have been revisited under more controlled
      conditions or have been subjected to meta-analysis. SUMMARY: The effects of
      ghrelin gene polymorphism, is a complex area of investigation, due to ghrelin's
      interplay with a host of various factors part of an integrative network. However,
      taken together, results suggest that there are no or nonsignificant effects of
      the common genetic variants. A better understanding of the network, probably by a
      systems biology type approach, will be necessary to assign the exact role played
      by gene polymorphism of the component of the ghrelin axis.

PMID- 24870815
TI  - Regulation of mouse microglia activation and effector functions by bone marrow
      derived mesenchymal stem cells.
AB  - Mesenchymal stems or stromal cells (MSCs) are rare multipotent cells with potent
      regenerative and immunomodulatory properties. Microglial cells (MGs) are
      specialized tissue macrophages of the central nervous system (CNS) that
      continuously survey their environment with highly motile extensions. Recently,
      several studies have shown that MSCs are capable of reprogramming microglia into
      an "M2-like" phenotype characterized by increased phagocytic activity and
      upregulated expression of anti-inflammatory mediators in vitro. However, the
      precise polarization states of microglia in the presence of MSCs under
      physiological or under inflammatory conditions remain largely unknown. In this
      study, we found that MSCs induce a mixed microglia phenotype defined as Arg1
      high, CD86-high, CD206-high, IL-10-high, PGE2-high, MCP-1/CCL2-high, IL-1beta
      moderate, NALP-3-low, and TNF-alpha-low cells. These MSC-elicited MGs have high
      phagocytic activity and antigen-presenting ability. Lipopolysaccharide is able to
      shape this microglia phenotype quantitatively, but not qualitatively in the
      presence of MSCs. This unique polarization state resembles a novel regulatory
      microglia phenotype, which might contribute to the resolution of inflammation and
      to tissue repair in the CNS. 

PMID- 24870816
TI  - Podocyte autophagic activity plays a protective role in renal injury and delays
      the progression of podocytopathies.
AB  - The progression of podocytopathies is quite variable among patients and the
      underlying reason for this remains unclear. Here, we report that autophagic
      activity in podocytes plays a critical role in controlling the progression of
      podocytopathies. Morphological and biochemical studies on renal biopsies from
      patients with minimal change disease (MCD) or focal segmental glomerulosclerosis
      (FSGS) showed that glomeruli, and in particular podocytes, from MCD patients had
      higher levels of Beclin1-mediated autophagic activity than glomeruli from FSGS
      patients. Repeat renal biopsies of MCD patients enabled tracking of podocyte
      autophagic activity and confirmed that patients maintaining high podocyte
      autophagic activity retained MCD status, whereas patients with decreased podocyte
      autophagic activity progressed to FSGS. Inhibition of autophagic activity, by
      knocking down Beclin1 or by treating with 3-methyladenine (3-MA) or chloroquine,
      enhanced puromycin aminonucleoside (PAN)-induced apoptosis of podocytes. In
      contrast, rapamycin-mediated promotion of autophagic activity decreased this
      apoptosis. In PAN-treated rats, inhibition of autophagy with 3-MA or chloroquine
      resulted in earlier onset and greater proteinuria, more extensive foot-process
      effacement, and reduction in podocyte markers, whereas rapamycin-mediated
      stimulation of autophagy led to decreased proteinuria and less severe foot
      process effacement, but higher expression of podocyte markers. This study
      demonstrates that podocyte autophagic activity plays a critical protective role
      in renal injury and that maintaining podocyte autophagic activity represents a
      potential therapeutic strategy for controlling the progression of
      podocytopathies.

PMID- 24870818
TI  - Cancer.

PMID- 24870819
TI  - Statistics: Attacking an epidemic.

PMID- 24870817
TI  - MRI of CNS fungal infections: review of aspergillosis to histoplasmosis and
      everything in between.
AB  - Fungal infections of the central nervous system (CNS) represent a wide spectrum
      of diseases with some common magnetic resonance imaging (MRI) features. Risk
      factors include immunocompromise of any cause and living in endemic areas. CNS
      infection occurs through hematogenous spread, cerebrospinal fluid seeding, or
      direct extension. MRI features include heterogeneous or ring reduced diffusion
      and weak ring enhancement. Angioinvasive aspergillosis is characterized by
      multifocal hemorrhagic lesions with reduced diffusion. Cryptococcosis results in
      gelatinous pseudocyst formation in the basal ganglia. Mucormycosis is
      characterized by frontal lobe lesions with markedly reduced diffusion.
      Candidiasis is usually manifest by numerous microabscesses of less than 3 mm
      occurring at the corticomedullary junction, basal ganglia, or cerebellum.
      Coccidioidomycosis often results in meningitis with contrast enhancement of the
      basal cisterns. Blastomycosis and histoplasmosis are rare infections with
      parenchymal abscesses or meningitis. Recognizing the imaging features of CNS
      infections allows for early, aggressive treatment of these otherwise rapidly
      fatal infections. 

PMID- 24870820
TI  - Therapy: This time it's personal.

PMID- 24870822
TI  - Nanotechnology: Deliver on a promise.

PMID- 24870823
TI  - Comparative biology: Naked ambition.

PMID- 24870821
TI  - Clinical trials: More trials, fewer tribulations.

PMID- 24870825
TI  - Developing world: Global warning.

PMID- 24870826
TI  - Bioinformatics: Big data versus the big C.

PMID- 24870824
TI  - Prevention: Air of danger.

PMID- 24870827
TI  - Perspective: Learning to share.

PMID- 24870828
TI  - Biology: Three known unknowns.

PMID- 24870829
TI  - Metal complexes and metalloproteases: targeting conformational diseases.
AB  - In recent years many metalloproteases (MPs) have been shown to play important
      roles in the development of various pathological conditions. Although most of the
      literature is focused on matrix MPs (MMPs), many other MPs have been demonstrated
      to be involved in the degradation of peptides or proteins whose accumulation and
      dyshomeostasis are considered as being responsible for the development of
      conformational diseases, i.e., diseases where non-native protein conformations
      lead to protein aggregation. It seems clear that, at least in principle, it must
      be possible to control the levels of many aggregation-prone proteins not only by
      reducing their production, but also by enhancing their catabolism. Metal
      complexes that can perform this function were designed and tested according to at
      least two different strategies: (i) intervening on the endogenous MPs by directly
      or indirectly modulating their activity; (ii) acting as artificial MPs, replacing
      or synergistically functioning with endogenous MPs. These two different
      bioinorganic approaches are widely represented in the current literature and the
      aim of this review is to rationally organize and discuss both of them so as to
      give a critical insight into these approaches and highlighting their limitations
      and future perspectives. 

PMID- 24870831
TI  - [Bone metabolism by sex hormones and gonadotropins].
AB  - Pathophysiology of postmenopausal osteoporosis has been considered due to
      deficiency of estrogen. However, it has been reported that the rate of bone mass
      loss during perimenopause is greater than that in postmenopause, probably due to
      increased FSH. From the recent knowledge of basic research on FSH, FSH can
      directly stimulate osteoclast formation and accelerate bone resorption. In
      contrast, FSH transgenic mice exhibit increased bone mass dependent on ovarian
      function. In this review, the controversies on the function of FSH in bone mass
      regulation will be discussed. 

PMID- 24870830
TI  - Injury news coverage, relative concern, and support for alcohol-control policies:
      an impersonal impact explanation.
AB  - Research on the impersonal impact hypothesis suggests that news (especially
      print) coverage of health and safety risks primarily influences perceptions of
      risk as a societal issue, and not perceptions of personal risk. The authors
      propose that the impersonal impact of news-impact primarily on concerns about
      social-level risks-will mediate effects of news stories on support for public
      health policies; such effects substantively matter as evidence suggests health
      policies, in turn, have important effects on protective behaviors and health
      outcomes. In an experiment using 60 randomly selected violent crime and accident
      news stories manipulated to contain or not contain reference to alcohol use as a
      causative factor, the authors find that the effect of stories that mention
      alcohol as a causative factor on support for alcohol-control policies is mediated
      by social-level concern and not by personal-level concern. In so doing, the
      authors provide a theoretical explanation as well as empirical evidence regarding
      the potential for news coverage-including breaking or episodic news-to influence
      health-related public policy. 

PMID- 24870832
TI  - [Thyroid hormone and skeletal metabolism].
AB  - The role of the hypothalamic-pituitary-thyroid axis is important in normal
      skeletal development, gain of bone mass, and regulation of adult bone metabolism.
      Hypothyroidism in childhood causes delayed bone maturation and growth disturbance
      and thyroid dysfunction in adult induces altered bone remodeling and an increased
      risk of bone fracture. Thyroid hormone actions in skeletal cells are mainly
      mediated by thyroid hormone receptor alpha (TRalpha) . The responses to thyroid
      hormone are regulated by type 2 and 3 iodothyronine deiodinase (DIO2 and DIO3) ,
      which convert prohormone (T4) to active hormone (T3) . Euthyroid status is
      necessary for the homeostasis of human bone metabolism. 

PMID- 24870833
TI  - [Glucocorticoid and bone].
AB  - Oral glucocorticoids are prescribed for a wide variety of medical disorders.
      Reduced bone formation is the key process in glucocorticoid-induced osteoporosis.
      Glucocorticoid-induced osteoporosis is characterized by relative dissociation
      between the BMD values and the fracture risk, which is higher than expected based
      on the BMD values. 2014 revised Japanese guidelines indicated that Age, GC dose,
      lumbar BMD, and prior fragility fractures were identified as factors predicting
      future fracture and each factor was scored according to the category. Since an
      age of 65 years or older, prednisolone dose of 7.5mg/day or more, and a history
      of fragility fracture are independent risk for future fractures, initiation of
      drug therapy can be decided more easily without evaluation of BMD by DXA when one
      of these risk factors exists. Alendronate and risedronate were recommended as
      first-line treatment and teriparatide (rDNA origin) , ibandronate, alfacalcidol
      and calcitriol were recommended as alternative option. 

PMID- 24870834
TI  - [Cytokine-mediated bone resorption].
AB  - Osteoclasts, the multinucleated cells that resorb bone, originate from monocyte
      macrophage lineage cells. Various hormones, cytokines and growth factors are
      involved in osteoclastogenesis, via interaction with osteoblasts. In this review,
      we summarize the regulatory mechanism of bone resorption by various cytokines
      derived from osteoblasts and hematopoietic inflammatory cells. 

PMID- 24870835
TI  - [Cytokines and osteogenesis].
AB  - Many cytokines associate with proliferation, differentiation and activation of
      osteoblasts which have an important role in osteogenesis. TGF-beta, BMP, IGF,
      FGF, Hedgehog, Notch, IL and WNT signaling pathways and their inhibitors have
      been revealed to correlate to osteogenesis, and those gene mutations have been
      shown to cause various bone disorders. It has been suggested that there are
      common pathways or crosstalk in these cytokine signaling each other, but
      mechanism of their complicated regulation on osteogenesis has been unclear. It
      was expected that the knowledge about these cytokines will apply to clinical
      therapies of bone diseases. 

PMID- 24870836
TI  - [Coupling and communication between bone cells].
AB  - Bone is constantly renewed by the balanced action of osteoblastic bone formation
      and osteoclastic bone resorption both of which mainly occur at the bone surface.
      This restructuring process called "bone remodeling" is important not only for
      normal bone mass and strength, but also for mineral homeostasis. Coupling has
      been understood as a balanced induction of osteoblastic bone formation in
      response to osteoclastic bone resorption. An imbalance of this coupling is often
      linked to various bone diseases. TGF-beta and IGF released from bone matrix
      during osteoclastic bone resorption are the favored candidates as classical
      coupling factor. Recently, several reports suggest that osteoclast-derived
      molecules/cytokines (clastokine) mediate directional signaling between
      osteoblasts and osteoclasts into the bone microenvironment. Thus, the elucidation
      of the regulatory mechanisms involved in bone cell communication and coupling is
      critical for a deeper understanding of the skeletal system in health and disease.

PMID- 24870837
TI  - [Role for PTHrP in bone and cartilage metabolism].
AB  - PTH-related peptide (PTHrP) is a widely distributed cytokine, which shares the
      cognate receptor PTHR1 with PTH. Originally identified as a causal factor of
      humoral hypercalcemia of malignancy twenty years ago, PTHrP is now recognized as
      a critical physiological regulator of various biological processes, including
      bone and cartilage metabolism. 

PMID- 24870838
TI  - [Cytokines and myeloma bone disease].
AB  - Multiple myeloma (MM) develops and expands almost exclusively in the bone marrow,
      and generates devastating bone destruction. MM cells produce a variety of
      cytokines to stimulate RANK ligand-mediated osteoclastogenesis and suppress
      osteoblastic differentiation from bone marrow stromal cells, leading to extensive
      bone destruction with rapid loss of bone. MM cells alter through bone destruction
      the microenvironment in bone where they colonize, which in turn favors tumor
      growth and survival, thereby forming a progressive vicious cycle between tumor
      expansion and bone destruction in MM. 

PMID- 24870839
TI  - [FGF23 and skeletal metabolism].
AB  - FGF23 is an endocrine FGF produced by osteocytes, which increases excretion of
      phosphate and suppresses the production of 1,25 (OH) 2D. Excessive action of
      FGF23 causes various forms of hypophosphatemic rickets/osteomalacia, while the
      loss of function of FGF23 results in the condition called familial
      hyperphosphatemic tumoral calcinosis. 1,25 (OH) 2D stimulates the production of
      FGF23, and the interaction between FGF23 and 1,25 (OH) 2D plays a central role in
      mineral homeostasis. In addition to the its roles in mineral homeostasis, recent
      studies have suggested the direct action of FGF23 on osteoblasts and
      chondrocytes. 

PMID- 24870840
TI  - [Renin-aldosterone and bone metabolism].
AB  - Among the components of the renin-angiotensin-aldosterone (RAAS) system, which
      controls blood pressure as well as fluid and electrolyte balance, renin,
      angiotensin II and its receptors AT1/2, and aldosterone and the mineralocorticoid
      receptor have been exploited as targets of drug development. Accumulating
      evidence suggests that the RAAS is linked, through a systemic/endocrine as well
      as a local loop, to inflammation, oxidative stress, cardiovascular and renal
      injury, and calcium and bone metabolism. 

PMID- 24870841
TI  - [Treatment of osteoporosis with PTH].
AB  - Teriparatide is an only available bone anabolic drug in practice. It is a N
      terminal fragment of parathyroid hormone (PTH) . Mode of actions of teriparatide
      is pharmacological but not physiological as it is administered to patients with
      osteoporosis. Physicians need to understand the fact that treatment with
      teriparatide is not just like a hormone replacement. They also should administer
      teriparatide to their patients after rigorous evaluation of its clinical
      superiority to other anti-osteoprosis drugs, because it is not classified as a
      first-line drug. 

PMID- 24870842
TI  - [Effects of growth hormone replacement therapy on bone metabolism].
AB  - Growth hormone (GH) as well as insulin like growth factor-1 (IGF-1) are essential
      hormones to maintain homeostasis of bone turnover by activating
      osteoblastogenesis and osteoclastogenesis. Results from GH replacement therapy
      for primary osteoporosis and adult-onset GH deficiency (AGHD) suggest that one
      year or more treatment period by this agent is required to gain bone mineral
      density (BMD) over the basal level after compensating BMD loss caused by dominant
      increase in bone resorption which was observed at early phase of GH treatment. A
      recent meta-analysis demonstrates the efficacy of GH replacement therapy on
      increases in BMD in male patients with AGHD. Additional analyses are needed to
      draw firm conclusions in female patients with AGHD, because insufficient amounts
      of GH might be administrated to them without considerations of influence of
      estrogen replacement therapy on IGF-1 production. Further observational studies
      are needed to clarify whether GH replacement therapy prevent fracture risk in
      these patients. 

PMID- 24870843
TI  - [Biologic agents for the treatment of rheumatic diseases].
AB  - Rheumatoid arthritis (RA) is a systemic inflammatory disease characterized by
      chronic synovitis and bone damage. Bone homeostasis is maintained by a balance
      between bone resorption and bone formation. It is also involved by immune systems
      and imbalance in immune system often results in pathological processes such as
      joint destruction as well as secondary osteoporosis. Proinflammatory cytokines
      such as TNF and IL-6 cause an imbalance in bone metabolism via direct and/or
      indirect effects on osteoclasts. However, the combination of methotrexate and
      biologic DMARDs targeting TNF and IL-6 have revolutionized the treatment of RA,
      producing significant improvements in clinical, radiographic, and functional
      outcomes that were not previously observed. Such progress in the treatment of RA
      has been expanded to other joint diseases including psoriatic arthritis,
      spodylarthritis and so on. 

PMID- 24870844
TI  - [Biological therapy for osteoporosis].
AB  - Osteoporosis is a disorder of bone formation and resorption balance. Advances in
      our knowledge of the molecular mechanisms of bone formation and resorption led to
      promising therapeutic targets for osteoporosis. In the novel biological drugs,
      denosumab, a monoclonal antibody against receptor activator of nuclear factor
      kappaB ligand (RANKL) has been clinically applied by positive effect on bone
      mineral density, negative effect on bone resorption, preventive effect on
      fragility fractures and safety. Odanacatib, a cathepsin K inhibitor is drawing
      attention as an antiresorptive drug which has lower bone resorption potency than
      bisphosphoneate. On the other hand, BHQ-880, an anti-Dickkopf-1 (Dkk-1) antibody
      and romosozumab (AMG-785) , an anti-sclerostin antibody which activate Wnt/beta
      catenin signaling pathway are drawing attention as bone formation accelerators
      with no bone resorption acceleration. Clinical studies of these drugs are now
      ongoing and their clinical applications are expected. 

PMID- 24870845
TI  - Problem parental care and teenage deliberate self-harm in young community adults.
AB  - Deliberate self-harm (DSH) in young people is a clinical and social problem
      related to early maltreatment but with little specificity in type of care or
      abuse determined. A community sample of 160 high-risk young people (aged 16-30)
      were the offspring of mothers' previously interviewed as vulnerable to major
      depression. The youth were interviewed to determine DSH (both suicidal and
      nonsuicidal), childhood maltreatment (using the Childhood Experience of Care and
      Abuse interview) and major depression (using SCID for DSMIV) before age 17.
      Around one fifth reported DSH; equal proportions were suicidal and nonsuicidal
      with a fourth of these with both. DSH was highly related to family context
      (single mother upbringing and family discord) and poor parental care (including
      antipathy, neglect, inadequate supervision, and role reversal). Highest odds
      ratios were for role reversal (OR = 17) and neglect (OR = 11). DSH was unrelated
      to any type of abuse. Logistic regression showed that role reversal, inadequate
      supervision, and teenage depression all modeled DSH. There was some specificity,
      with single mother upbringing, role reversal, and inadequate supervision
      predicting nonsuicidal DSH, and neglect and role reversal alone predicting
      suicidal DSH. Role reversal remained a key predictor for both types of DSH when
      controls were applied. Poor childhood care, which has implications for
      problematic emotion regulation and empoverished social development, needs to be
      understood to improve interventions and treatment for DSH in young people.

PMID- 24870846
TI  - Personality vulnerabilities in adolescent suicidality: The mediating role of
      psychological distress.
AB  - The research literature consistently indicates that self-criticism is related to
      suicidality. Evidence for the role of dependency, however, is more controversial.
      This study examines the extent to which these personality vulnerabilities are
      mediated by psychological distress in the prediction of suicidality. As part of a
      study of adolescent psychopathology, a sample of 260 Portuguese adolescents (148
      [56.9 %] female and 112 [43.1%] male), ranging in age from 15 to 18 years (M =
      16.32, SD = 1.19) completed measures of personality, suicidal behavior, and
      current distress, in counterbalanced order. The measures were: self-criticism and
      dependency from the Depressive Experiences Questionnaire for Adolescents; two
      psychological distress scales, social withdrawal from the Youth Self Report and
      depression from the Center for Epidemiologic Studies of Depression Scale; and a
      measure of suicidality from the Suicide Behaviors Questionnaire Revised.
      Structural equation modeling indicated that self-criticism and dependency were
      both significantly associated with suicidality. Psychological distress, however,
      as measured by withdrawal and depression, fully mediated these relationships, but
      did not moderate them. The authors conclude that adolescents with higher levels
      of self-criticism and dependency are at greater risk for experiencing intense
      psychological distress-high levels of social withdrawal and depression-that
      account for their vulnerability to suicide risk.

PMID- 24870847
TI  - Perfectionism dimensions as predictors of symptom dimensions of obsessive
      compulsive disorder.
AB  - The correlation between obsessive-compulsive disorder (OCD) and perfectionism is
      well documented, yet it remains unclear if dimensions of perfectionism vary as a
      function of OCD symptom dimensions. To this end, the present study investigated
      the unique associations between dimensions of perfectionism (i.e., concern over
      mistakes, doubts about actions, personal standards, parental criticism, parental
      expectations, and organization) and OCD symptom dimensions (i.e., hoarding,
      washing, checking, ordering, obsessing, and neutralizing). The study included
      adult patients with OCD (N = 46) from a residential OCD treatment program.
      Consistent with previous research, doubts about actions was a significant
      predictor of overall OCD severity and OCD checking symptoms. The organization
      dimension of perfectionism was a significant predictor of OCD ordering symptoms.
      The current study provides evidence for the unique relationships between OCD
      symptoms and perfectionism dimensions that encourage a movement toward greater
      phenotypic specificity within existing models of OCD.

PMID- 24870848
TI  - Association between level of personality organization as assessed with theory
      driven profiles of the Dutch Short Form of the MMPI and outcome of inpatient
      treatment for personality disorder.
AB  - The association between level of personality organization as assessed by theory
      driven profile interpretation of the MMPI (Hathaway & McKinley, 1943) Dutch Short
      Form and treatment outcome was investigated in a naturalistic follow-up study
      among 121 psychotherapy inpatients who had been treated for their severe
      personality pathology. Treatment outcome was measured with the Brief Symptom
      Inventory (De Beurs & Zitman, 2006). Personality organization was associated with
      severity of psychopathology at baseline, the end of treatment, and 36 months
      after baseline. At 36 months after baseline, all patients except those with the
      high-level borderline organization profile and the psychotic borderline profile
      maintained their improvement. Contrary to expectations, (a) personality
      organization did not differentiate between patients with successful and
      unsuccessful out-comes, and (b) patients with a neurotic personality organization
      did not respond better than those with a borderline personality organization.
      Because of the small N, conclusions are tentative.

PMID- 24870849
TI  - Shame proneness in symptom dimensions of obsessive-compulsive disorder.
AB  - Although one study has noted that shame may play a significant role in anxiety
      disorders (Fergus, Valentiner, McGratch, & Jencius, 2010), the literature does
      not address the appearance of shame within specific dimensions of obsessive
      compulsive disorder (OCD). In this study, shame is assessed within four common
      symptom dimensions of OCD: contamination, harm, unacceptable thoughts, and
      symmetry. The authors hypothesized that shame would be significantly related to
      unacceptable thoughts and harm, but not other dimensions. Ninety-one individuals
      with OCD completed the Dimensional Obsessive-Compulsive Scale (measuring severity
      of OCD symptom dimensions) and the Test of Self-Conscious Affect (assessing shame
      proneness). Results indicated a positive significant relationship between shame
      and harm, but not unacceptable thoughts. Additionally, a significant correlation
      was found between shame and symmetry. This is possibly due to a relationship
      between perfectionism and symmetry (Wu & Cortesi, 2009). These findings suggest
      that shame is related to certain dimensions of OCD and may deserve consideration
      in relation to treatment.

PMID- 24870853
TI  - Editorial-a revived focus on the praying mantises (Insecta: Mantodea).

PMID- 24870854
TI  - Guest editorial.

PMID- 24870855
TI  - A historical review of nomenclature and high-level classification of praying
      mantises (Mantodea), including a provisional checklist of the names associated to
      suprageneric ranks.
AB  - The history of high-level classification of praying mantids is presented. The
      various historical stages that helped to construct our current knowledge on
      Mantodea taxonomy and systematic are highlighted through an extensive literature
      review, from pre-Linnaean times to the present. A provisional checklist of the
      names associated to suprageneric ranks (family, subfamily and tribe) is also
      provided, in addition to some remarks on the future efforts that need to be
      conducted in Mantodea research. 

PMID- 24870856
TI  - Four new species of Ciulfina Giglio-Tos, 1915 (Mantodea: Liturgusidae,
      Liturgusinae) from the Northern Territory, Australia .
AB  - The praying mantid genus Ciulfina Giglio-Tos includes many small, gracile tree
      trunk dwelling species found throughout northern Australia. Four new species of
      Ciulfina: C. annecharlotteae, C. herbersteinae, C. ianrichardi, and C.
      terrymariceae are formally described on the basis of male genital morphology. 

PMID- 24870857
TI  - A revision of Rhodomantis Giglio-Tos, 1917 (Mantodea: Mantidae: Mantinae).
AB  - The genus Rhodomantis Giglio-Tos is revised. A total of nine species are
      recognised. Seven new species, R. helenae, R. kimberley, R. macula, R.
      microptera, R. mitchell, R. napier, and R. rentzi are described. Rhodomantis
      carinicollis Werner and R. gracilis Tindale are new synonyms of R. queenslandica
      Sjostedt. 

PMID- 24870858
TI  - A revision of Apteromantis (Mantodea: Mantidae, Amelinae): a comprehensive
      approach to manage old taxonomic and conservation problems .
AB  - The genus Apteromantis Werner, 1931 comprises two species of wingless mantids,
      the Iberian A. aptera (Fuente, 1894) and the North African A. bolivari (Werner,
      1929). Although A. aptera and A. bolivari have been traditionally considered as
      separate and valid species, their external appearance is quite similar and no
      comprehensive taxonomic study has analyzed their morphological and genetic
      characteristics. This taxonomic uncertainty has important implications for
      conservation because A. aptera is considered an Iberian endemic and the only
      praying mantis protected by international laws. In this study, we apply a
      comprehensive approach, including quantitative morphological and molecular
      analyses, to shed new light on the taxonomic and conservation status of the genus
      Apteromantis and the putative species. We have found that the Iberian and North
      African specimens analyzed herein significantly differ in female head shape, male
      genitalia morphology and several other traits related to body size. Molecular
      data suggest the presence of two main lineages, with sequence divergence rates of
      approximately 4 %, which are within the range reported for other well defined
      insect species. Overall, this study supports that A. aptera and A. bolivari are
      valid species despite their ecological and morphological similarity and
      highlights the importance of comprehensive approaches to resolve old taxonomic
      and conservation problems. 

PMID- 24870859
TI  - A review of the research on Canary Islands praying mantises (Mantodea).
AB  - For many years researchers studying the fauna of the Canary Islands have only
      sparsely treated the charismatic insect order of praying mantises (Mantodea). By
      studying the known literature it becomes obvious that there are several
      inconsistencies regarding mantodean taxonomy as well as the number of actual
      species and their distribution within the archipelago. In the present
      contribution, the literature treating the Canary Island Mantodea fauna is
      thoroughly reviewed, and the distribution of the ten known Mantodea species is
      presented with additional comments on the taxonomic problems. The taxonomy and
      distribution of the Canary Island Amelinae has been causing some confusion in the
      literature and is therefore discussed for a better understanding of the
      composition of this group. So far, seven species of Amelinae (two species of
      Ameles Burmeister and five species of Pseudoyersinia Kirby) are recognized for
      the Canary Islands. A careful survey of the taxonomic literature indicates that
      there is a substantial degree of variability in this group, which may have led to
      frequent misidentifications. This is reflected by the inconsistent literature
      data on the distribution of several Pseudoyersinia species within the
      archipelago. A crucial amendment and clarification is provided regarding the date
      of description (1838) of Ameles gracilis (Brulle) and Ameles limbata (Brulle) as
      it varies in the literature. Nomenclatural changes regarding the homonymy of
      Mantis limbata Brulle and Mantis limbata Hahn, previously proposed by Kocak &
      Kemal (2008), are rejected and discussed in detail. One of the Mantodea species,
      Empusa pennata (Thunberg), is frequently mentioned in the literature to be
      present on the Canary Islands, but after carefully reviewing the literature data
      it is evident that this species has never actually been found on any of the
      islands. The aim of this publication is to lay a basis for future research on the
      Mantodea fauna of the Canary Islands, their phylogenetic placement and history of
      dispersal. This is even more important as the archipelago is a European endemism
      hot spot for praying mantises and these basic parameters are crucial for
      implementing plans regarding conservation strategies on the islands. 

PMID- 24870860
TI  - A case of the higher-level classification of praying mantises (Mantodea)
      obscuring the synonymy of Majangella Giglio-Tos, 1915 (Liturgusidae,
      Liturgusinae) and Ephippiomantis Werner, 1922 (Hymenopodidae, Acromantinae).
AB  - The praying mantis genus Majangella Giglio-Tos, 1915 is taxonomically treated
      with a re-description of the genus and the two included species, M. moultoni
      Giglio-Tos, 1915 and M. carli Giglio-Tos, 1915. The genus Ephippiomantis Werner,
      1922 is newly determined to be the junior synonym of Majangella Giglio-Tos, 1915
      based on morphology. The species for which the genus name Ephippiomantis was
      erected, E. ophirensis Werner, 1922, is re-described and now included within
      Majangella. This synonymy was determined herein as the direct result of erroneous
      higher-level placement of Majangella within the Majanginae by Giglio-Tos and was
      not recognized even after the genus was moved to within Liturgusidae. Action is
      now taken to move Majangella from within Liturgusidae to within the Hymenopodidae
      subfamily of Acromantinae, which is supported by morphological and molecular
      data. A key to the three species is provided along with habitus images, images of
      the head, pronotum, and foreleg, and illustrations of the male genitalia. Species
      distributions are presented and locality coordinates are provided in print as
      well as being available for download as a KML file viewable in Google Earth. 

PMID- 24870862
TI  - An annotated checklist of the praying mantises (Mantodea) of Borneo, including
      the results of the 2008 scientific expedition to Lanjak Entimau Wildlife
      Sanctuary, Sarawak .
AB  - We present the first checklist of praying mantids (Mantodea) of Borneo, with
      special reference to the specimens collected during the Scientific Expedition to
      Lanjak Entimau Wildlife Sanctuary 2008. With 118 confirmed species in 56 genera
      (including subgenera), Borneo is the island with the highest mantodean diversity
      known to date. In Lanjak Entimau 38 specimens representing 17 genera and 18
      species were collected around the station lights and in surrounding secondary and
      primary forest. A new synonymy in the genus Deroplatys is established. The
      observed diversity patterns among Bornean mantids are discussed with reference to
      the biogeographic history of the Sunda Shelf since the Miocene. 

PMID- 24870861
TI  - A remarkable new species of Mythomantis Giglio-Tos, 1916 from northern Borneo,
      with notes on the systematics of Deroplatyinae Westwood, 1889 (Mantodea:
      Mantidae).
AB  - A conspicuous new species of praying mantid, Mythomantis serrata sp. nov., from
      the Malaysian part of Borneo is described and illustrated. A key to the three
      known species of the genus Mythomantis and their known geographic distribution is
      provided. Several morphological characters, most notably those in the male
      genitals, suggest a close relationship between Mythomantis and the Southeast
      Asian genera Pseudempusa and Deroplatys. As a consequence, we propose to transfer
      Mythomantis from Angelinae to Deroplatyinae, and Pseudempusa from Miomantinae
      Rivetinini to Deroplatyinae, while removing Brancsikia from this subfamily. 

PMID- 24870863
TI  - A taxonomic revision of Otomantis Bolivar, 1890 (Mantodea: Hymenopodidae,
      Acromantinae) with description of five new species.
AB  - The African genus Otomantis Bolivar, 1890, is taxonomically treated via the re
      description of its species on the basis of new morphological features (pronotum
      and male genitalia). Five new species, O. centralis sp. n. from D. R. of Congo
      and Angola, O. gracilis sp. n. from D. R. of Congo, O. trimacula sp. n. from
      Zambia and Malawi, O. bolivari sp. n. from Kenya and Tanzania and O. minima sp.
      n. from South Africa are described. The taxonomic position of the syntypes of O.
      capirica Giglio-Tos is revised. A lectotype is designated for the female of O.
      capirica. The female of O. rendalli (Kirby) and the male of O. aurita (Saussure &
      Zehntner) are described for the first time. Also provided are many new localities
      for all nominal species.  A key to the species of Otomantis is included for both
      male and female, each key fully illustrated. Finally, observations on species
      distributions and relationships are presented. 

PMID- 24870864
TI  - A new genus and species of Mantoididae (Mantodea) from the Brazilian and
      Venezuelan Amazon, with remarks on Mantoida Newman, 1838 .
AB  - Paramantoida amazonica n. gen. & n. sp. is described from North Amazon. The new
      genus is characterized by having anterior femora without postero-ventral spines
      or with 1-2 spinules (small spines) at most. Additional remarks on the genus
      Mantoida, following the examination of several primary types, are also presented.
      As a result, the identity of Manti-llica beieri Kaltenbach, 1957 as a member of
      Mantoida is herein confirmed, whereas other synonyms previously established for
      other species of Mantillica in relation to Mantoida are discarded. 

PMID- 24870865
TI  - A revision of Miobantia Giglio-Tos, 1917 (Mantodea: Thespidae, Miobantiinae),
      with molecular association of dimorphic sexes and immature stages.
AB  - The Neotropical praying mantis genus Miobantia Giglio-Tos, 1917 currently
      includes six species with a complex taxonomic history. Although frequently found
      in the atlantic forest of Brazil, little is known about these species. Several
      obstacles make it difficult identifying these mantids, including high levels of
      sexual dimorphism and both sexes known only for one of the six currently known
      species. The taxonomic boundaries among the species of Miobantia are proposed in
      this work, through a cladistic analysis using 99 morphological characters, and
      the analysis of sequence variation of approximately 700 bp of the mithocondrial
      gene COI for association of dimorphic sexes and nymphs. Additionally, an
      investigation of intraspecific variation is conducted based on a large number of
      specimens of M. fuscata (Giglio-Tos) in oder to choose the most relevant features
      for the separation of the species to be used in taxonomic descriptions and
      identification keys. The male of M. aptera Giglio-Tos, and the females of M.
      ciliata (Stal) and M. fuscata are described for the first time, and redescription
      of the males of these and the female of M. aptera, are provided based on
      additional data. Miobantia nebulosa (Giglio-Tos) is herein redescribed (male
      genitalia included) and proposed as a junior synonym of M. rustica (Fabr.).
      Additionally, four new species are here described, totaling nine species for the
      genus: M. immanis n. sp. (Espirito Santo, Brazil), M. arctissima n. sp. (Espirito
      Santo, Brazil), M. sulista n. sp. (Santa Catarina and Rio Grande do Sul, Brazil;
      San Bernardino, Paraguay), and M. nordestina n. sp. (Bahia, Brazil); both sexes
      of all new species are described, except for M. arctissima, which remain known by
      males only. Identification keys and figures of diagnostic features are provided
      for both males and females of all valid species. The species distribution is
      mapped according to literature data and 50 new records. 

PMID- 24870866
TI  - On the identity and taxonomic status of the enigmatic mantid Thespoides bolivari
      Chopard, 1916 (Mantodea: Mantidae, Angelinae).
AB  - Chopard (1916) published a brief paper in which he cited and described a number
      of praying mantis species from the neotropics. The specimens he studied belonged
      to the prominent Spanish Entomologist Ignacio Bolivar y Urrutia (1850-1944),
      whose collection is now housed at the Museo Nacional de Ciencias Naturales in
      Madrid (MNCN), Spain (Izquierdo et al. 1997). In this publication Chopard
      described Thespoides bolivari Chopard, 1916 as a new genus and species, based on
      a single male obtained by French coleopterist Rene Oberthur in Cauca, Colombia.
      According to Chopard (1916) the specimen was remarkable for having, among other
      features, an abdomen that is markedly shorter than the rest of its body-certainly
      an unusual morphological trait among the Mantodea. Chopard assigned Thespoides to
      the Miopteryginae (Thespidae), but it was later reassigned (together with Angela
      Serville, 1839 as the "Angelae group") to the subfamily Schizocephalinae
      (Mantidae) by Giglio-Tos (1927). Current classifications consider the Angelinae
      to comprise a distinct subfamily of the Mantidae, with Thespoides and Angela as
      the only representatives of this subfamily with a Neotropical distribution (e.g.
      Ehrmann 2002). 

PMID- 24870867
TI  - The new Southeast Asian goblin spider genus Aposphragisma (Araneae, Oonopidae):
      diversity and phylogeny.
AB  - The new genus Aposphragisma (Araneae, Oonopidae, Oonopinae) comprising the new
      species A. baltenspergerae, A. borgulai, A. brunomanseri, A. confluens, A. dayak,
      A. dentatum, A. draconigenum, A. hausammannae, A. helvetiorum, A. kolleri, A.
      menzi, A. monoceros, A. nocturnum, A. retifer, A. rimba, A. salewskii, A.
      scimitar, A. sepilok and A. stannum is described. It is characterised by very
      hard bodied, strongly sclerotized species with completely armoured prosoma and
      strongly sclerotized ventral and dorsal abdominal scuta. Aposphragisma gen. nov.
      is placed within the Gamasomorpha-group sensu Saaristo (2001). Descriptions and
      illustrations are given for all new species. A phylogenetic analysis based on 40
      characters using Prethopalpus fosuma, Gamasomorpha asterobothros, G. cataphracta,
      G. seximpressa, Xestaspis biflocci, X. kandy and X. paulina as outgroup-taxa and
      Cortestina thaleri (Oonopidae, Sulsulinae) as the root is presented and
      discussed. Furthermore it is shown that females of Aposphragisma gen. nov.
      possess complex internal genitalia. The members of the new genus are ground
      dwelling litter inhabitants restricted to Southeast Asian lowland and montane
      forests, with more than 60% of the species only known from single localities.
      They are presumed to be negatively affected by the massive destruction of
      pristine forest habitats within their range. This work has been conducted within
      the framework of the Planetary Biodiversity Inventory (PBI) of Oonopidae (see
      http://research.amnh.org/oonopidae). 

PMID- 24870868
TI  - A world revision of the bee fly tribe Usiini (Diptera, Bombyliidae) Part 2: Usia
      sensu stricto.
AB  - This is the second part of a world revision of the genera Usia Latreille and
      Parageron Paramonov, of the tribe Usiini Becker, and covers the pale-haired
      species, the Usia sensu stricto group. Usia sensu stricto as defined here
      contains 24 species of which 16 species fall into two monophyletic groups, the U.
      lata group with 10 species and the U. florea group with six species. Eight
      species cannot be placed in either of these two groups, four of them form two
      pairs of sibling species while the remaining four species have no clear
      affinities. Of the 25 formerly available names that belong in Usia sensu stricto,
      U. putilla Becker stat. rev., previously synonymised under U. angustifrons, is
      reinstated as a full species. U. sicula Egger syn. nov., is synonymised under U.
      manca Loew, U. anus Becker syn. nov., is synonymised under U. vestita Macquart
      and U. claripennis Macquart syn. nov., is synonymised under U. atrata
      (Fabricius). Usia vicina Macquart, formerly placed as a synonym of U. atrata, is
      shown to be a junior synonym of U. aenea Rossi. Five new species are described,
      U. anatoliensis sp. nov., U. annetteae sp. nov., U. greatheadi sp. nov., U.
      maghrebensis sp. nov. and U. cornigera sp. nov. Both the male and female
      genitalia are illustrated in detail for 21 species, female only in the cases of
      U. calva Loew and U. notata Loew and male only for U. incognita Paramonov.

PMID- 24870869
TI  - Diversity, host association, and cocoon variability of reared Indian
      Microgastrinae (Hymenoptera: Braconidae).
AB  - Nearly 3,500 specimens of microgastrine wasps (Hymenoptera: Braconidae) were
      reared during caterpillar surveys undertaken in 2010-2013 across India, covering
      16 States and one Union Territory (Andaman & Nicobar islands), and deposited in
      the National Bureau of Agriculturally Important Insects, Bangalore, India. The
      caterpillar inventory recovered over two hundred morpho-species within 22
      families of Lepidoptera and yielded 90+ morpho-species of microgastrine wasps
      distributed among 13 genera: Apanteles Forster, Buluka de Saeger, Cotesia
      Cameron, Diolcogaster Ashmead, Distatrix Mason, Dolichogenidea Viereck, Fornicia
      Brulle, Glyptapanteles Ashmead, Microgaster Latreille, Microplitis Forster,
      Neoclarkinella Rema & Narendran, Parapanteles Ashmead, and Protapanteles Ashmead.
      Records of hyperparasitoids are also included: Mokrzeckia menzeli Subba Rao
      (Pteromalidae), Pachyneuron groenlandicum (Holmgren) (Pteromalidae), Pediobius
      foveolatus (Crawford) (Eulophidae), Trichomalopsis thekkadiensis Sureshan &
      Narendran (Pteromalidae), Eurytoma sp., and Pediobius sp. (Eurytomidae). The
      present study adds eight new host records and provides illustrations of 40
      species of wasps (including types). A comprehensive list of microgastrine genera,
      host caterpillar species, host plants, cocoon colour, structure and spinning
      pattern, and hyperparasitoids is provided. Numerous photographs of parasitized
      caterpillars, cocoons (number/arrangement), associated host plants, and adult
      wasps are also provided. The Indian species Deuterixys ruidus (Wilkinson, 1928)
      is transferred to the genus Cotesia based on the shape and sculpture of the first
      and second mediotergites: Cotesia ruidus (Wilkinson) comb. nov. Microgaster
      carinicollis Cameron is transferred to Microplitis, based on examination of first
      and second mediotergites, length of metatibia spurs, and size of metaxocoxa:
      Microplitis carinicollis (Cameron) stat. rev. 

PMID- 24870870
TI  - Revision of the Western Palaearctic Diplazontinae (Hymenoptera, Ichneumonidae).
AB  - I revise the subfamily Diplazontinae to include 99 Western Palaearctic species,
      review morphological characters useful for species delimitation and
      identification, and clarify the status of some morphologically similar taxa using
      molecular approaches. Illustrated, dichotomous keys to the Western Palaearctic
      genera and species of the subfamily are presented, and the utility of the
      molecular markers CO1 and ITS2 for species delimitation in Diplazontinae is
      discussed. Seven new species are described, Diplazon flixi sp. nov., Diplazon
      nordicus sp. nov., Diplazon parvus sp. nov., Diplazon zetteli sp. nov.,
      Eurytyloides umbrinus sp. nov., Sussaba roberti sp. nov., and Woldstedtius bauri
      sp. nov. The Nearctic Sussaba cultriformis (Ashmead), formerly a subspecies of
      Sussaba dorsalis (Holmgren), is raised to species rank. The following taxa are
      valid species and hereby removed from synonymy: Episemura ensata (Bauer), stat.
      rev.; Homotropus frontorius (Thunberg), stat. rev.; Syrphoctonus desvignesii
      (Marshall), stat. rev.; Syrphophilus scabriculus (Holmgren), stat. rev.; and
      Tymmophorus suspiciosus (Brischke), stat. rev. Nineteen new synonyms are
      established: Bioblapsis mallochi Rotheray of Bioblapsis cultiformis (Davis), syn.
      nov.; Bioblapsis tricincta Ashmead of Syrphophilus scabriculus (Holmgren), syn.
      nov.; Diplazon bachmaieri Diller of Diplazon angustus Dasch, syn. nov.; Diplazon
      fechteri Diller of Diplazon cascadensis Dasch, syn. nov.; Homocidus brevis Hedwig
      of Homotropus pictus (Gravenhorst); Homocidus rubiginosum Schmiedeknecht of
      Enizemum scutellare (Lange), syn. nov.; Homocidus simulans Stelfox of Homotropus
      collinus (Stelfox), syn. nov.; Homotropus crassicrus Thomson and Homotropus nudus
      Dasch of Homotropus dimidiatus (Schrank), syn. nov.; Homocidus asyntactus
      Schmiedeknecht of Homotropus crassicornis Thomson, syn. nov.; Homocidus subopacus
      Stelfox and Homotropus quadrangularis Dasch of Homotropus frontorius (Thunberg),
      syn. nov.; Homocidus impolitus Stelfox of Homotropus pallipes (Gravenhorst), syn.
      nov.; Homotropus incisus Thomson and Homotropus reflexus Morley of Homotropus
      pectoralis (Provancher), syn. nov.; Tryphon nigricornis Zetterstedt, a former
      synonym of H. dimidiatus Schrank, is a synonym of Homotropus pictus
      (Gravenhorst), syn. nov.; Homotropus fraudulentus Dasch and Homotropus neopulcher
      Horstmann of Syrphoctonus desvignesii (Marshall), syn. nov.; Homotropus eximius
      Habermehl of Syrphoctonus tarsatorius (Panzer), syn. nov. The following new
      combinations are established: Bioblapsis cultiformis (Davis), comb. nov.;
      Homotropus collinus (Stelfox), comb. nov.; Homotropus dimidiatus (Schrank), comb.
      nov.; Homotropus frontorius (Thunberg), comb. nov.; Homotropus pectoralis
      (Provancher), comb. nov.; Homotropus strigator (Fabricius), comb. nov.;
      Homotropus sundevalli (Holmgren), comb. nov. The present revision is the first
      comprehensive treatment of the Western Palaearctic Diplazontinae, provides the
      basis for taxonomic, faunistic, ecological and evolutionary studies in these
      hoverfly parasitoids, and exemplifies an integrative approach to systematics and
      taxonomy.

PMID- 24870871
TI  - A phase 2 study of brentuximab vedotin in patients with relapsed or refractory
      CD30-positive non-Hodgkin lymphomas: interim results in patients with DLBCL and
      other B-cell lymphomas.

PMID- 24870872
TI  - A phase I study of panobinostat in combination with ICE (Ifosfamide, Carboplatin
      and Etoposide) in patients with relapsed or refractory classical Hodgkin lymphoma
      (cHL).

PMID- 24870873
TI  - FDG-PET adapted sequential therapy with brentuximab vedotin and augmented ICE
      followed by autologous stem cell transplant for relapsed and refractory Hodgkin
      lymphoma.

PMID- 24870874
TI  - Mature response data from a phase 2 study of PI3K-delta inhibitor idelalisib in
      patients with double (rituximab and alkylating agent)-refractory indolent B-cell
      non-Hodgkin lymphoma (iNHL).

PMID- 24870875
TI  - Phase II trial of brentuximab vedotin for CD30+ cutaneous T-cell lymphomas and
      lymphoproliferative disorders.

PMID- 24870876
TI  - Lenalidomide in combination with R-CHOP (R2-CHOP) in patients with high burden
      follicular lymphoma: phase 2 study.

PMID- 24870877
TI  - Reduced-intensity conditioning (RIC) and allogeneic stem cell transplantation
      (allo-SCT) for relapsed/refractory Hodgkin lymphoma (HL) in the brentuximab
      vedotin era: favorable overall and progression-free survival (OS/PFS) with low
      transplant-related mortality (TRM).

PMID- 24870878
TI  - Combination biologic therapy without chemotherapy as initial treatment for mantle
      cell lymphoma: multi- center phase II study of lenalidomide plus rituximab.

PMID- 24870879
TI  - Commentary.

PMID- 24870880
TI  - Study of the effect of nickel heavy metals on some physiological parameters of
      Catharanthus roseus.
AB  - Plants, in their life cycle, are usually exposed to various kinds of non
      biological stresses including heavy metals. One of these heavy metals is nickel
      which affects many physiological processes of plants. Studies have shown that the
      changes in planting conditions can affect the qualitative and quantitative
      features of Catharanthus roseus; therefore, creating stressful conditions (e.g.
      NiCl2) can be an effective way to investigate the changes. In this research, we
      investigated the effect of 0, 2.5, 5, 10, 25 and 50 mM concentrations of NiCl2 on
      the degree of catalase enzyme activity, amount of proline aggregation and
      photosynthetic parameters on seeds of pink variety of C. roseus. The results
      indicated that the degree of catalase enzyme activity and the amount of proline
      aggregation increased in plants which were exposed to NiCl2 treatments,
      especially in high concentrations, while the total protein decreased. The stress
      of Ni also affected photosynthetic parameters, and decreased the amount of
      pigments, as well as the efficiency of photosystem II.

PMID- 24870881
TI  - A quick, simple, robust method to measure the acidity of ionic liquids.
AB  - Introduced here is a quick, simple, robust method to measure acidity in ionic
      liquid (IL) systems by the use of the NMR-probe mesityl oxide. Acidity
      corresponding to a Hammett acidity of -1 to -9 can be measured reliably using
      this technique, a range that vastly exceeds that of any single UV-vis probe. 

PMID- 24870882
TI  - New species of the genus Chydaeus from China, Nepal, Myanmar, and Thailand, with
      remarks on species previously described (Coleoptera: Carabidae: Harpalini).
AB  - Ten new species of the genus Chydaeus Chaudoir, 1854 are described: C. dissimilis
      sp. n. (the bedeli species group) from the Doi Inthanon Mountain, Chiang Mai
      Province, Thailand; C. shaanxiensis sp. n. (the kasaharai species group) from the
      Daba Shan Mountain Range, southern Shaanxi, China; C. kabaki sp. n. (the
      kasaharai species group) from southern Sichuan, China; C. weishanensis sp. n.
      (the kasaharai species group) from the northern part of Wuliang Shan, western
      Yunnan, China; C. belousovi sp. n. (the kasaharai species group) from the south
      western Yunnan, China; C. putaoensis sp. n. (the kasaharai species group) from
      the environments of Putao, the northernmost part of Myanmar; C. ganeshensis sp.
      n. (the irvinei species group) from the Ganesh Himal, Central Nepal; C.
      chuliensis sp. n. (the semenowi species group) from the Manaslu Himal, Central
      Nepal; C. wuliangensis sp. n. (the semenowi species group) from the northern part
      of Wuliang Shan, western Yunnan, China; C. luxiensis sp. n. (the semenowi species
      group) from the environments of Luxi, western Yunnan, China. New data about the
      distribution of the following species are provided: C. kasaharai Ito, 2002, C.
      shunichii Ito, 2006, C. semenowi (Tschitscherine, 1899), C. convexus Ito, 2002,
      C. baoshanensis Kataev & Liang, 2012, and C. obtusicollis Schauberger, 1932. The
      following taxa are reported for the first time: Chydaeus semenowi, C.
      obtusicollis and C. bedeli interjectus Kataev & Schmidt, 2002 from the Indian
      state Arunachal Pradesh, C. bedeli difficilis Kataev & Schmidt, 2002 from
      Myanmar, and C. similis Kataev & Schmidt, 2002 from the Chinese provinces Shaanxi
      and Chongqing. 

PMID- 24870883
TI  - The tadpoles of nine Cameroonian Leptodactylodon species (Amphibia, Anura,
      Arthroleptidae).
AB  - We describe and compare the tadpoles of nine Leptodactylodon species from
      Cameroon. The tadpoles of Leptodactylodon bicolor, L. mertensi, L. ovatus, L.
      perreti and L. ventrimarmoratus are herein reinvestigated, partly based on larger
      series than previously available. In addition we present first descriptions for
      the tadpoles of L. boulengeri, L. erythrogaster, L. ornatus, and L. cf.
      polyacanthus. The morphology of these exotrophic, lotic and neustonic tadpoles is
      discussed in comparison with other stream-dwelling tadpoles. Based on the assumed
      biology of these tadpoles, living in interstices of gravel or debris, the
      functioning of several special morphological features, in particular the funnel
      mouth of Leptodactylodon tadpoles, are interpreted. 

PMID- 24870884
TI  - Two new species of Simulium (Gomphostilbia) (Diptera: Simuliidae) from Cameron's
      Highlands, Peninsular Malaysia, with keys to 21 species of the Simulium asakoae
      species-group.
AB  - Two new black fly species, Simulium (Gomphostilbia) brinchangense and S. (G.)
      tanahrataense, are described on the basis of reared adult females, males, pupae
      and larvae from Cameron's Highlands, Peninsular Malaysia. These new species are
      assigned to the asakoae species-group within Simulium (Gomphostilbia) and
      taxonomic notes are given to distinguish each new species from six known species
      in Malaysia. Revised keys to identify all 21 species including 13 species from
      other countries are provided for females, males, pupae and mature larvae. The
      species diversity of the asakoae species-group in Cameron's Highlands is briefly
      noted. 

PMID- 24870886
TI  - Petalophthalmus papilloculatus sp. nov. (Crustacea: Mysida: Petalophthalmidae), a
      new bathyal suprabenthic mysid from the Galicia Bank (NE Atlantic Ocean).
AB  - A new species of the genus Petalophthalmus (Crustacea: Mysida: Petalophthalmidae)
      is described, based on specimens collected from the Galicia Bank (northeastern
      Atlantic Ocean). This species can be distinguished from the other species of the
      genus Petalophthalmus by the presence of an ocular papilla on its eyes. P.
      papilloculatus sp. nov. is morphologically close to the cosmopolitan species P.
      armiger Willemoes-Suhm, 1875, but can be easily distinguished by the presence of
      an ocular papilla, the longer antennal scales bearing an apical lobe, the unique
      chitinous ridge on the molar process, the outwards lengthening of the three
      cuspidate setae on the outer margin of the uropodal exopod and the armature of
      the telson. This new species lives on fine and very fine sandy bottoms at the
      bank flanks, between 1536 and 1809 m depths. Probably related to the special
      biogeographic characteristics of seamounts, the morphological affinity between
      the new species and P. armiger supports the hypothesis on a common ancestry and
      recent divergence between both deep sea mysids. An identification key to world
      species of Petalophthalmus is provided. 

PMID- 24870885
TI  - A new species of Siphonoecetes Kroyer, 1845 Siphonoecetes (Centraloecetes)
      bulborostrum sp. nov. (Crustacea, Amphipoda, Ischyroceridae) from the western
      Mediterranean, coast of Iberian Peninsula.
AB  - An undescribed species of Siphonoecetes Kroyer, 1845 was found on Mediterranean
      coast of Iberian Peninsula. It was collected at the depth of 10 and 15 m near
      Alicante. Though it was previously found in Chafarinas Islands, this new species
      was not named and fully described. In the present paper, Siphonoecetes
      (Centraloecetes) bulborostrum sp. nov. is described. The species belongs to
      Centroloecetes subgenus, since it possesses bulbous ventroapical projection on
      peduncle of uropod 1 in males and a row of long pectinate setae on distal margin
      of peduncle of uropod 3. Siphonoecetes (Centraloecetes) bulborostrum sp. nov.
      (Crustacea, Amphipoda, Ischyroceridae) is easily distinguishable from the other
      Siphonoecetes reported in Iberian Mediterranean coast by presence of bulbous
      subrostral projection. 

PMID- 24870887
TI  - A new species of Sangeeta Viraktamath from China (Hemiptera: Cicadellidae:
      Megophthalminae).

PMID- 24870888
TI  - Notes on the butterflies "described" in 1929 by Prof. Woon-Young Chun from Hainan
      Island, China (Lepidoptera, Papilionoidea).

PMID- 24870889
TI  - A new species of Arbomia Sato & Wang (Lepidoptera, Geometridae, Ennominae) from
      Guangxi, Southern China.

PMID- 24870890
TI  - The Black-tailed Antechinus, Antechinus arktos sp. nov.: a new species of
      carnivorous marsupial from montane regions of the Tweed Volcano caldera, eastern
      Australia.
AB  - We describe a new species of dasyurid marsupial within the genus Antechinus that
      was previously known as a northern outlier of Dusky Antechinus (A. swainsonii).
      The Black-tailed Antechinus, Antechinus arktos sp. nov., is known only from areas
      of high altitude and high rainfall on the Tweed Volcano caldera of far south-east
      Queensland and north-east New South Wales, Australia. Antechinus arktos formerly
      sheltered under the taxonomic umbrella of A. swainsonii mimetes, the widespread
      mainland form of Dusky Antechinus. With the benefit of genetic hindsight, some
      striking morphological differences are herein resolved: A. s. mimetes is more
      uniformly deep brown-black to grizzled grey-brown from head to rump, with
      brownish (clove brown-raw umber) hair on the upper surface of the hindfoot and
      tail, whereas A. arktos is more vibrantly coloured, with a marked change from
      greyish-brown head to orange-brown rump, fuscous black on the upper surface of
      the hindfoot and dense, short fur on the evenly black tail. Further, A. arktos
      has marked orange-brown fur on the upper and lower eyelid, cheek and in front of
      the ear and very long guard hairs all over the body; these characters are more
      subtle in A. s. mimetes. There are striking genetic differences between the two
      species: at mtDNA, A. s. mimetes from north-east New South Wales is 10% divergent
      to A. arktos from its type locality at Springbrook NP, Queensland. In contrast,
      the Ebor A. s. mimetes clades closely with conspecifics from ACT and Victoria. A.
      arktos skulls are strikingly different to all subspecies of A. swainsonii. A.
      arktos are markedly larger than A. s. mimetes and A. s. swainsonii (Tasmania) for
      a range of craniodental measures. Antechinus arktos were historically found at a
      few proximate mountainous sites in south-east Queensland, and have only recently
      been recorded from or near the type locality. Even there, the species is likely
      in low abundance. The Black-tailed Antechinus has plausibly been detrimentally
      affected by climate change in recent decades, and will be at further risk with
      increasing warming trends.  

PMID- 24870891
TI  - A new trans-Andean Stick Catfish of the genus Farlowella Eigenmann & Eigenmann,
      1889 (Siluriformes: Loricariidae) with the first record of the genus for the rio
      Magdalena Basin in Colombia.
AB  - A new species of Farlowella is described from El Carmen de Chucuri in the
      Departamento de Santander, western flank of the Cordillera Oriental, rio
      Magdalena Basin, Colombia. Farlowella yarigui n. sp. differs from its congeners
      in lateral body plate morphology, abdominal cover, cephalic hypertrophied
      odontodes, and details of coloration. This is the first verifiable record of the
      genus in the Magdalena drainage. Aspects of natural history and implications of
      this finding are provided concerning the state of knowledge of the fishes of the
      rio Magdalena Basin. Previous records of Farlowella gracilis in the rio Cauca
      basin are examined and herein considered erroneous, rendering the new species the
      only representative of the genus in the Magdalena-Cauca system. A key to species
      of Farlowella from Colombia is provided. 

PMID- 24870892
TI  - Nematodes from terrestrial, freshwater and brackish water habitats in Belgium: an
      updated list with special emphasis on compost nematodes.
AB  - A study of nematodes from a semi-artificial and controlled composting process in
      Eastern Flanders revealed 35 taxa, 21 of which were new records for Belgium. An
      updated checklist of free-living, plant-parasitic and entomopathogenic nematodes
      from terrestrial, freshwater and brackish water habitats in Belgium is presented.
      The Belgian non-marine nematofauna comprises 418 taxa, representing 4 subclasses,
      14 orders, and 76 families. In total 127 new records were added: i.e. 21 from the
      newly explored compost habitat, 7 from freshwater samples and 99 from published
      data in literature. 

PMID- 24870893
TI  - Palaearctic Hoplitis bees of the subgenera Chlidoplitis and Megahoplitis
      (Megachilidae, Osmiini): biology, taxonomy and key to species.
AB  - Chlidoplitis and Megahoplitis are closely related Palaearctic subgenera of the
      osmiine bee genus Hoplitis (Megachilidae) containing nine and two species,
      respectively. Analysis of female pollen loads and field observations suggest that
      all species are pollen specialists. Whereas the H. (Chlidoplitis) species are
      probably all narrowly oligolectic and exclusively collect pollen on Allium
      (Alliaceae), Haplophyllum (Rutaceae), Reseda (Resedaceae), Teucrium (Lamiaceae),
      Trifolium (Fabaceae) or Hedysareae (Fabaceae), the H. (Megahoplitis) species show
      a close affinity to Carduoideae (Asteraceae) as pollen hosts. The few data
      available suggest that the H. (Chlidoplitis) species nest in preexisting insect
      burrows in the ground and use either chewed leaves or mud as nesting material.
      The nesting biology of the subgenus Megahoplitis remains unknown. The taxonomic
      revision of the subgenera Chlidoplitis and Megahoplitis revealed the existence of
      two undescribed species: H. (Chlidoplitis) haplophylli spec. nov. from
      southeastern Central Asia and Hoplitis (Chlidoplitis) allii spec. nov. from the
      Levant. Identification keys for the species of both subgenera are given including
      the hitherto unknown male of H. (Megahoplitis) bombiformis.  

PMID- 24870894
TI  - Palaearctic osmiine bees of the genera Hofferia and Stenoheriades (Megachilidae,
      Osmiini): biology, taxonomy and key to species.
AB  - Hofferia and Stenoheriades are closely related, species-poor genera of the
      osmiine bees (Megachilidae). Analysis of female pollen loads and field
      observations indicate that species of both genera have a strong affinity to
      Asteraceae as pollen hosts. Both genera use insect burrows in dead wood as
      nesting site, and Hofferia schmiedeknechti was found to build cell walls and nest
      plug with resin partly mixed with small pebbles. The taxonomic revision of the
      Palaearctic Hofferia and Stenoheriades species revealed the existence of a still
      undescribed species in the Levant, Stenoheriades levantica spec. nov..
      Stenoheriades hofferi (Tkalcu, 1984) is synonymized with S. coelostoma (Benoist,
      1935), which is distinct from S. asiatica (Friese, 1921), and Heriades integra
      Benoist, 1934, formerly considered a Stenoheriades species, is synonymized with
      Osmia (Hoplosmia) scutellaris Morawitz, 1868. Keys for the delimitation of
      Hofferia and Stenoheriades from the other Palaearctic osmiine bee genera and for
      the identification of the Palaearctic species are given.  

PMID- 24870895
TI  - Two new combinations and a key to the species of the genus Earota Mulsant & Rey
      (Coleoptera: Staphylinidae: Aleocharinae).
AB  - Earota babai (Sawada, 1989), comb. nov. and Earota koreana (Pasnik, 2001), comb.
      nov. are transferred from the genera Pelioptera Kraatz, 1857 and Aloconota
      Thomson, 1858, respectively. Earota babai is recorded from the Korean Peninsula
      for the first time and E. koreana is a new addition to South Korea.
      Redescriptions, habitus photographs, illustrations of diagnostic characters of
      these two species and a key to the known species of the genus Earota Mulsant &
      Rey, 1874 are provided to facilitate identification. 

PMID- 24870896
TI  - Two new quill mite species of the family Syringophilidae (Acari: Prostigmata)
      parasitising the house sparrow Passer domesticus (L.) (Aves: Passeriformes).
AB  - Two new quill mite species of the family Syringophilidae, Picobia passeri sp.
      nov. and Krantziaulonastus dubinini sp. nov., are described from quills of the
      body feathers of the house sparrow Passer domesticus (L.) (Passeriformes:
      Passeridae) from the European part of Russia. 

PMID- 24870897
TI  - Systematic review of the firefly genus Amydetes Illiger, 1807 (Coleoptera:
      Lampyridae), with description of 13 new species.
AB  - A systematic review of Amydetes Illiger, 1807, based on examination of the type
      material. We fix A. fastigiata Illiger, 1807 as the type-species of the genus;
      redescribe the genus and six out of eight species; describe 13 new species; and
      provide illustrations and a key to species. We place A. vigorsi Westwood, 1830
      syn. n. and A. gorhami Kuntzen, 1912 syn. n. in synonymy with A. fastigiata; A.
      suturalis Pic, 1925 syn. n. and A. brasiliensis Pic, 1925 in synonymy with A.
      apicalis; and A. flavicollis Olivier, 1888 syn. n. in synonymy with A.
      lucioloides Olivier, 1888. We report the first record of Amydetes from Venezuela
      and Argentina, and establish more precise distributions of the studied species.
      We describe the circadian period of A. apicalis (diurnal), A. fastigiata and
      Amydetes bellorum sp. nov. (nocturnal) and discuss the circadian diversity of the
      genus. Fronto-clypeus, antenna, labrum, maxillary palpomere, prothorax,
      mesosternum, lanterns, abdominal segment VIII and terminalia were structures that
      provided important characters for delimitation and diagnosis of the species. 

PMID- 24870898
TI  - Potamotrygon limai, sp. nov., a new species of freshwater stingray from the upper
      Madeira River system, Amazon basin (Chondrichthyes: Potamotrygonidae).
AB  - Potamotrygon limai, sp. nov., is described from the Jamari River, upper Madeira
      River system (Amazon basin), state of Rondonia, Brazil. This new species differs
      from congeners by presenting unique polygonal or concentric patterns formed by
      small whitish spots better defined over the posterior disc and tail-base regions.
      Potamotrygon limai, sp. nov., can be further distinguished from congeners in the
      same basin by other characters in combination, such as two to three rows of
      midtail spines converging to a single irregular row at level of caudal sting
      origin, proportions of head, tail and disc, patterns of dermal denticles on
      rostral, cranial and tail regions, among other features discussed herein.
      Potamotrygon limai, sp. nov., is most similar to, and occurs sympatrically with,
      P. scobina, and is distinguished from it by lacking ocellated spots on disc, by
      its characteristic polygonal pattern on posterior disc, a comparatively much
      shorter and broader tail, greater intensity of denticles on disc, more midtail
      spine rows at tail-base, and other features including size at maturity and
      meristic characters. Potamotrygon limai, sp. nov., is also distinguished from
      other species of Potamotrygon occurring in the Amazon region, except P. scobina,
      by presenting three angular cartilages (vs. two or one). This new species was
      discovered during a detailed taxonomic and morphological revision of the closely
      related species P. scobina, and highlights the necessity for thorough and all
      embracing taxonomic studies, particularly in groups with pronounced endemism and
      morphological variability. 

PMID- 24870899
TI  - Thysanoptera intercepted in the Netherlands on plant products from Ethiopia, with
      description of two new species of the genus Thrips.
AB  - An overview is given of 18 Thysanoptera species found on Ethiopian cut flowers,
      cuttings and vegetables during import inspection in the Netherlands. Consignments
      consisted mostly of cut flowers, in total belonging to twelve plant genera.
      Details on geographical distribution and host plants of the thrips encountered
      are given, and two are newly described: T. cacuminis sp. n. and T. dezeeuwi sp.
      n. The results do not give any serious indication of increased invasiveness by
      Ethiopian Thysanoptera.  

PMID- 24870900
TI  - Two new species of Nyctelia Latreille (Coleoptera: Tenebrionidae) from
      Argentinean Patagonia with zoogeographical and ecological remarks.
AB  - Two new species of the genus Nyctelia Latreille (Pimeliinae: Nycteliini) from
      Argentinean Patagonia, N. sulcogranata sp. nov. and N. recteplicata sp. nov., are
      described. Distributional maps, habitus, photographs and illustrations of
      genitalic features for these two new species are included, with comparisons to
      other known species of the genus. A discussion is presented on distributional
      habitat records and biogeography. 

PMID- 24870901
TI  - New genus of the tribe Diestramimini (Orthoptera: Rhaphidophoridae) from
      Thailand.
AB  - Mimadiestra gen. nov. (type species: M. biloba sp. nov.) is described from
      Thailand. Megadiestramima Storozhenko et Gorochov, 1992 and Leodiestramima
      Storozhenko, 2009, stat. nov. are considered as separate genera, therefore, three
      new combinations are proposed: Leodiestramima exculta (Gorochov, 1998), comb.
      nov., L. lecta (Gorochov, 1998), comb. nov., L. orlovi (Gorochov, 1994), comb.
      nov. A key to genera of the tribe Diestramimini is given.  

PMID- 24870902
TI  - Two new species of the genus Gonioctena Chevrolat (Coleoptera, Chrysomelidae,
      Chrysomelinae) from Sichuan, China.
AB  - Two new species of Gonioctena Chevrolat, G. sichuana sp. n. and G. metallica sp.
      n., are described from Sichuan Province, China. Diagnostic characters and
      illustrations are provided. Ovoviviparity is recorded in G. metallica sp. n. 

PMID- 24870903
TI  - Palaearctic Hoplitis bees of the subgenus Stenosmia (Megachilidae, Osmiini):
      biology, taxonomy and key to species.
AB  - Hoplitis bees of the Palaearctic subgenus Stenosmia (Megachilidae) inhabit
      deserts and semideserts between southern Spain and eastern Asia. They nest in
      excavated burrows in the soil and collect pollen from plant taxa that typically
      grow in desert areas, such as Frankenia (Frankeniaceae), Peganum (Nitrariaceae),
      Tamarix (Tamaricaceae) or Zygophyllum (Zygophyllaceae). The taxonomic revision of
      the subgenus Stenosmia revealed the existence of four undescribed species:
      Hoplitis desertorum spec. nov. from the Levant, H. crassipunctata spec. nov. and
      H. dispersipunctata spec. nov. from Central Asia, and H. gobiensis spec. nov.
      from the Gobi desert. Hoplitis denticulata (Zanden, 1992) is synonymized with H.
      jordanica (Warncke, 1991), and Hoplitis xinjiangense (Wu, 2004), formerly
      considered a H. (Stenosmia) species, is removed from this subgenus. The type
      species of the subgenus Stenosmia Michener is fixed as H. crassipunctata spec.
      nov., which has been misidentified as H. flavicornis (Morawitz, 1877). Keys for
      the identification of the H. (Stenosmia) species are given. 

PMID- 24870904
TI  - The high-level classification of skinks (Reptilia, Squamata, Scincomorpha).
AB  - Skinks are usually grouped in a single family, Scincidae (1,579 species)
      representing one-quarter of all lizard species. Other large lizard families, such
      as Gekkonidae (s.l.) and Iguanidae (s.l.), have been partitioned into multiple
      families in recent years, based mainly on evidence from molecular phylogenies.
      Subfamilies and informal suprageneric groups have been used for skinks, defined
      by morphological traits and supported increasingly by molecular phylogenies.
      Recently, a seven-family classification for skinks was proposed to replace that
      largely informal classification, create more manageable taxa, and faciliate
      systematic research on skinks. Those families are Acontidae (26 sp.), Egerniidae
      (58 sp.), Eugongylidae (418 sp.), Lygosomidae (52 sp.), Mabuyidae (190 sp.),
      Sphenomorphidae (546 sp.), and Scincidae (273 sp.). Representatives of 125 (84%)
      of the 154 genera of skinks are available in the public sequence databases and
      have been placed in molecular phylogenies that support the recognition of these
      families. However, two other molecular clades with species that have long been
      considered distinctive morphologically belong to two new families described here,
      Ristellidae fam. nov. (14 sp.) and Ateuchosauridae fam. nov. (2 sp.).
      Morphological diagnoses and species content for all nine families of skinks
      (Scincomorpha) are presented. 

PMID- 24870905
TI  - A revision of the callipallenid genus Pseudopallene Wilson, 1878 (Pycnogonida,
      Callipallenidae).
AB  - Analysis of three northern hemisphere Boreal-Arctic species of Pseudopallene has
      shown that those species are morphologically distinguishable from their congeners
      in Australian waters. The holotypes of Australian species Pseudopallene laevis,
      Pseudopallene ambigua and Pseudopallene harrisi are compared with each other and
      with additional material from southern Australia. Sixteen species of
      Pseudopallene are assigned to a new genus Meridionale. Meridionale dubia is
      assigned to species inquirenda. The genus Cordylochele Sars, 1888 is resurrected.
      A diagnosis of each genus is provided along with additional figures. A brief
      summary of the systematic position of Pseudopallene up to the present time is
      provided. Three species are temporarily assigned to species incertae sedis
      pending further review. 

PMID- 24870906
TI  - Three new Nannastacidae (Crustacea: Cumacea) species from a Caribbean mesophotic
      ecosystem.
AB  - Examination of substrata from the mesophotic reefs of Mona Island, Puerto Rico
      yielded 3 new species of cumaceans, all from the family Nannastacidae: Cumella
      achimae sp. nov., C. victoriae sp. nov. and Nannastacus craciuni sp. nov. The 3
      new species bring the total of new cumacean taxa described from the mesophotic
      reefs of US Caribbean to 9, highlighting the potential of mesophotic reefs as a
      biodiversity hotspot. For the first time we report the genus Nannastacus from the
      Caribbean Sea.  

PMID- 24870907
TI  - A new species of Piaroa (Schizomida: Hubbardiidae) from Venezuela, with taxonomic
      notes on the genus.
AB  - A new species belonging to the schizomid genus Piaroa Villarreal, Giupponi and
      Tourinho, 2008 is described from north-western Venezuela. A complementary
      description of Piaroa guipongai Villarreal and Garcia, 2012 is provided including
      SEM pictures of relevant structures of both sexes. A key for males of Piaroa and
      Colombiazomus Armas and Delgado-Santa, 2012 is included. The presence of Dm3
      setae on Hubbardiidae is discussed. 

PMID- 24870908
TI  - Three new species of the genus Paederus Fabricius (Coleoptera: Staphylinidae:
      Paederinae) from China.
AB  - Three new species of the genus Paederus Fabricius from China are described:
      Paederus bilobus sp. nov. from Hainan, P. lateralis sp. nov. from Yunnan, and P.
      brunneolus sp. nov. from Xinjiang.  

PMID- 24870909
TI  - First record of genus Nabicerus Kwon (Hemiptera: Cicadellidae: Idiocerinae) from
      China, with descriptions of two new species.
AB  - Nabicerus Kwon is reported from China for the first time based on two new
      species, N. dentimus and N. baculatus spp. nov., and a new Chinese record of N.
      fuscescens (Anufriev, 1971). Species of this genus are described and illustrated.
      A redescription of the genus is provided together with a checklist and key to
      species for the separation of males.  

PMID- 24870910
TI  - The male of Sauris mouliniei (Legrand, 1971) comb. n. (Lepidoptera: Geometridae:
      Larentiinae: Trichopterygini), an endemic Inner Seychelles moth.

PMID- 24870911
TI  - Further records of Amphipoda from Baltic Eocene amber with first evidence of prae
      copulatory behaviour in a fossil amphipod and remarks on the taxonomic position
      of Palaeogammarus Zaddach, 1864.
AB  - Two pieces of Baltic amber with amphipod inclusions were studied. One of them
      contained approximately twenty individuals identified as belonging to the extinct
      genus Palaeogammarus and described as P. debroyeri sp. nov. Interestingly, among
      the individuals there are two pairs preserved in an evident prae-copula position.
      This is the first finding of such mating behaviour in fossil amphipods. Based on
      this behavioural trait and on the observed morphological features, we conclude
      that the genus Palaeogammarus should be placed in Gammaridae and not in
      Crangonyctidae. The second amber piece contains two individuals identified as
      belonging to the still extant genus Synurella and described as S. aliciae sp.
      nov.  

PMID- 24870912
TI  - Squat lobsters (Crustacea: Anomura) from Mauritanian waters (West Africa), with
      the description of a new species of Munidopsis.
AB  - This paper is the result of the study of a squat lobsters collection obtained
      along the Mauritanian coast, between 91 and 1867 m depth, during the 'MAURIT'
      surveys carried out in the period from 2007 to 2010. Eumunida bella de Saint
      Laurent & Macpherson, 1990 (Chirostyloidea) and six species of Munida and
      Munidopsis (Galatheoidea) are reported in the present work.A new species,
      Munidopsis anaramosae n. sp. collected off northwestern Banc d'Arguin at 1000
      1012 m depth, is described and illustrated. The presence of an eyespine that
      arises distally from the middle end of the cornea, walking legs merus spinose on
      dorsal and ventral margins and cheliped merus ventrally unarmed distinguish it
      from related species. Munida chunii Balss, 1913 is redescribed here and the new
      records of Munida guineae Miyake & Baba, 1970, M. speciosa von Martens, 1878 and
      Munidopsis chunii Balss, 1913 extend their geographical distribution northwards,
      and in the case of the last species, increase its bathymetric range. 

PMID- 24870913
TI  - The grandiculus- and metacarpalis-group of the genus Apanteles Foerster, 1862
      (Hymenoptera, Braconidae, Microgastrinae) from China, with descriptions of eight
      new species.
AB  - Two species groups (the grandiculus- and the metacarpalis-group) of genus
      Apanteles Foerster (Hymenoptera, Braconidae, Microgastrinae) from China are
      revised and keyed, with eight new species, namely, A. muticiculus Liu & Chen, sp.
      n., A. parvus Liu & Chen, sp. n. and A. flavicapus Liu & Chen, sp. n. of the
      grandiculus-group; A. transtergum Liu & Chen, sp. n., A. malleus Liu & Chen, sp.
      n., A. dumosus Liu & Chen, sp. n. A. cosmopterygivorus Liu & Chen, sp. n. and A.
      incurvus Liu & Chen, sp. n. of the metacarpalis-group, and two newly recorded
      species of the metacarpalis-group described and illustrated. Keys to the Chinese
      species of these two species-groups are provided. 

PMID- 24870914
TI  - A new species and notes on Perlidae (Plecoptera) from Parana and Santa Catarina
      States, southern Brazil.
AB  - Specimens of Perlidae (Plecoptera) deposited in the Entomological Collection
      "Padre Jesus S. Moure" of the Universidade Federal do Parana and additional
      material recently collected in Parana and Santa Catarina states, Brazil were
      studied. Six previously described species were identified, Anacroneuria debilis
      (Pictet, 1841), A. cathia Froehlich, 2002, A. polita (Burmeister, 1839), A.
      trimacula Jewett, 1959, Kempnyia neotropica (Jacoson and Bianchi, 1905) and K.
      colossica (Navas, 1934). Additionally, a new species, Anacroneuria iguazu n. sp
      is described. 

PMID- 24870915
TI  - A new species of the genus Rhabdophis Fitzinger, 1843 (Squamata: Colubridae) from
      Guangdong Province, southern China.
AB  - A new species, Rhabdophis guangdongensis sp. nov., is described from the
      Guangdong Province, China. It can be easily distinguished from other known
      congeners by cyt b and c-mos sequences, and by the following combination of
      morphological characters: body size small; head distinct from the neck; 20
      maxillary teeth, the three most posterior teeth strongly enlarged, and not
      separated by diastemata from other teeth; six supralabials, the third and fourth
      touching the eye; seven infralabials, the first four in contact with anterior
      chin shields; dorsal scales in 15 rows throughout the body, weakly keeled, the
      outer row smooth; 126 ventrals; 39 paired subcaudals; anal scale divided; 44
      pairs of narrow dorsolateral black cross-bars on body and 15 pairs on tail; body
      and tail with two dorsolateral longitudinal brownish-red lines, respectively with
      a series of white spots in cross-bars. The description of this new species brings
      the total number of described species of this genus to 21 and represents the
      tenth known Rhabdophis species in China. 

PMID- 24870916
TI  - Four new species and first nominal record of Chasmogenus Sharp, 1882 (Coleoptera:
      Hydrophilidae) from Brazil.
AB  - The genus Chasmogenus Sharp, 1882 (Hydrophilidae: Acidocerinae) is recorded from
      Brazil for the first time. Four new species are described and illustrated from
      the Southeastern Region of the country: C. fluminensis sp. nov. (Rio de Janeiro
      State), C. lilianae sp. nov. (Rio de Janeiro State), C. itatiaia sp. nov. (Minas
      Gerais and Rio de Janeiro States), and C. ubatuba sp. nov. (Sao Paulo State).
      Chasmogenus sapucay Fernandez, 1986 is recorded for the first time from Northern
      and Southeastern Brazil. Notes on morphology and an updated key for the South
      American species are provided. 

PMID- 24870917
TI  - New record and redescription of the monotypic genus Comefulvius Carvalho &
      Carpintero, 1985 (Hemiptera: Heteroptera: Miridae: Cylapinae) .
AB  - Comefulvius chingonus Carvalho & Carpintero, the only representative of the genus
      Comefulvius, previously known only from Cordoba Province, Argentina, is recorded
      from Ecuador. Redescription of Comefulvius is given along with color photographs
      of the adult and illustrations of the male genitalia. 

PMID- 24870918
TI  - A synoptic review of the genus Stagmomantis (Mantodea: Mantidae).
AB  - Stagmomantis is a remarkable genus within the Mantodea, being relatively species
      rich and geographically widespread.  Yet, the number of species within the genus
      remains curiously unresolved.  The present synoptic review surveys the literature
      on Stagmomantis to identify named species for which scientific consensus exists,
      as well as to summarize basic biological information for each species, including
      geographic distribution, morphological features, and sex-specific biometric data.
      The review identifies 23 consensus taxa within Stagmomantis:  22 separate
      species, with one of these species, S. montana, split into two subspecies (S. m.
      montana and S. m. sinaloae).   The review indicates morphological features that
      may prove to be diagnostic for a given species, particularly when examined in
      conjunction with male genitalia.  Such features include dark spots on the
      anterior femur (S. amazonica, S. centralis, S. marginata, S. nahua, S. venusta,
      S. vicina), spines or denticulations on the anterior coxa (S. colorata, S.
      montana montana, S. parvidentata, S. theophila), and dark bands on abdominal
      tergites (S. californica, S. colorata, S. domingensis).  Color variation of
      certain features with respect to body coloration, such as stigma coloration and
      body and leg markings, requires more attention. Information on life history,
      reproduction, and ecology are summarized, particularly for temperate populations
      of S. carolina and S. limbata.  While the 23 consensus taxa represent a robust
      appraisal of the existing literature, some taxonomic uncertainties remain.  The
      status of two species are somewhat unclear (S. marginata and S. tolteca), calling
      for taxonomic evaluation.  Furthermore, proposed within-genus groupings deserve
      examination, as do possible subdivisions within some species (e.g., S. limbata,
      S. parvidentata).  Information on basic morphology and biometry remains
      incomplete for nearly all species.  Extreme examples are S. amazonica, S.
      costalis, and S. paraensis, for which females have not been described.  Live
      animal research on life history, behavior, and ecology is needed for all species,
      with the possible exceptions of S. carolina and S. limbata.  By reconciling
      species assignments and consolidating biological information for the 23 consensus
      taxa, this synoptic review promises to guide subsequent systematic and
      phylogenetic investigations of the genus Stagmomantis.  

PMID- 24870919
TI  - Ultrastructural analysis and polymorphisms in Coarazuphium caatinga (Coleoptera:
      Carabidae: Zuphiini), a new Brazilian troglobitic beetle.
AB  - Coarazuphium caatinga sp. n. occurs in limestone caves located in Campo Formoso
      municipality, in the Brazilian Caatinga (Bahia, Brazil). The new species is close
      to C. formoso although they are morphologically distinct by the elytra sinuosity,
      which is more pronounced in C. caatinga; the aedeagus is more tapered at the tip
      in this last species. Important traits found in C. caatinga are the variable size
      presented by the eyes, and the remarkable variability of body pigmentation among
      specimens; both traits do not seem to be correlated. Coarazuphium Gnaspini, P.,
      Vanin, S.A. & Godoy, N.M., 1998, species exhibit advanced troglomorphic
      characters in comparison to other Brazilian cave beetles, as are increased extra
      optic sensory structures, presence of particular sensilla, and sensory and
      gustatory receptors. These characters are not detected under routine microscopy
      and thus require ultrastructural methods for their study.

PMID- 24870920
TI  - New taxa and notes of some described species of Agraeciini (Orthoptera:
      Tettigoniidae: Conocephalinae) from Malay Peninsula.
AB  - Four new species from three genera of Agraeciini from Malay Peninsula are
      described: Paragraecia temasek sp. n., Peracca mirzai sp. n., Peracca
      macritchiensis sp. n. from Singapore, and Lichnofugia malaya sp. n. from
      Peninsular Malaysia. The first records and descriptions of the female of Liara
      alata Ingrisch, 1998 and the male of Paragraecia gracilis Ingrisch, 1998 are
      given. 

PMID- 24870921
TI  - Redescription of a poorly known epialtid crab Pugettia pellucens Rathbun, 1932
      (Crustacea: Decapoda: Brachyura: Majoidea) and description of a new species from
      Sagami Bay, Japan.
AB  - A poorly known epialtid crab species, Pugettia pellucens Rathbun, 1932, is
      redescribed and a closely allied new species P. vulgaris n. sp. is described and
      illustrated on the basis of material from Sagami Bay, Japan. Pugettia pellucens
      was originally described as a subspecies of P. quadridens (De Haan, 1839), but it
      is confirmed that the taxon is distinct from P. quadridens. The superficially
      similar Pugettia vulgaris n. sp. can be distinguished from P. pellucens by
      several morphological characters. The new species is also similar to P. elongata
      Yokoya, 1933, and P. intermedia Sakai, 1938, but can also be separated by various
      carapace and gonopodal characters.

PMID- 24870922
TI  - New species of Creagrutus Gunther (Characiformes: Characidae) from rio Tapajos
      basin, Brazil, with comments on its phylogenetic position.
AB  - Creagrutus nigrotaeniatus n. sp. is described from the rio Juruena basin, upper
      rio Tapajos system, Mato Grosso State, Brazil. Creagrutus nigrotaeniatus differs
      from its congeners by having the dentigerous surface of the premaxilla
      longitudinally elongate from ventral view, 4-5 post-anal scales and 2-4 maxillary
      teeth. The new species also has the anterior margin of hyomandibula straight or
      slightly concave which is a unique condition within the genus, and possesses a
      series of non-exclusive osteological modifications (e.g. medial opening of the
      dentary foramen located distinctly anteroventral to the tip of Meckel's
      cartilage; anterior portion of the laterosensory canal segment in first
      infraorbital terminating distinctly posterior to the anterior margin of this
      bone; presence of the third posttemporal fossa within the epioccipital; one
      epural present). A comparison with Caiapobrycon tucurui is provided and the
      placement of the new species within Creagrutus and its close relationship with C.
      cracentis, C. gephyrus, and C. maxillaris are discussed.

PMID- 24870923
TI  - Revision of the genus Delenda Croissandeau, 1891 (Coleoptera: Staphylinidae:
      Pselaphinae).
AB  - The genus Delenda Croissandeau, 1891 is revised and redescribed. The taxonomic
      position of the Delenda frivaldszkyi Reitter, 1893 is discussed, and its species
      status is resurrected. Delenda carthago Croissandeau, 1891, and D. frivaldszkyi
      Reitter, 1893 are redescribed. One new species D. rhodopensis sp. n. is
      described.  

PMID- 24870924
TI  - Distribution of Acanthephyra brevicarinata Hanamura, 1984 and A. brevirostris
      Smith, 1885 (Crustacea: Decapoda: Caridea: Acanthephyridae), in Pacific Mexico.
AB  - Two species of the Acanthephyridae, Acanthephyra brevicarinata Hanamura, 1984,
      and A. brevirostris Smith, 1885, are reported for the Pacific coast of Mexico.
      The number of known localities for A. brevicarinata, a species endemic to the
      eastern Pacific, is increased from 24 to 70 and the number of specimens on
      records from 160 to 363. New distribution limits are provided for this species,
      from 25 degrees 02'N; 112 degrees 54'W to 16 degrees 58'N; 100 degrees 55'W,
      including the central and northern Gulf of California from 28 degrees 01'N; 112
      degrees 17'W southwards. Based on previous information related to its capture and
      the morphology of its first larval stage, A. brevicarinata is considered to be
      part of the nektobenthic fauna. New records for A. brevirostris confirm its
      presence within the Gulf of California.  

PMID- 24870926
TI  - Lead optimization of a novel series of imidazo[1,2-a]pyridine amides leading to a
      clinical candidate (Q203) as a multi- and extensively-drug-resistant anti
      tuberculosis agent.
AB  - A critical unmet clinical need to combat the global tuberculosis epidemic is the
      development of potent agents capable of reducing the time of multi-drug-resistant
      (MDR) and extensively-drug-resistant (XDR) tuberculosis therapy. In this paper,
      we report on the optimization of imidazo[1,2-a]pyridine amide (IPA) lead compound
      1, which led to the design and synthesis of Q203 (50). We found that the amide
      linker with IPA core is very important for activity against Mycobacterium
      tuberculosis H37Rv. Linearity and lipophilicity of the amine part in the IPA
      series play a critical role in improving in vitro and in vivo efficacy and
      pharmacokinetic profile. The optimized IPAs 49 and 50 showed not only excellent
      oral bioavailability (80.2% and 90.7%, respectively) with high exposure of the
      area under curve (AUC) but also displayed significant colony-forming unit (CFU)
      reduction (1.52 and 3.13 log10 reduction at 10 mg/kg dosing level, respectively)
      in mouse lung. 

PMID- 24870928
TI  - Impact of organisational characteristics on turnover intention among care workers
      in nursing homes in Korea: a structural equation model.
AB  - OBJECTIVE: The aim of the present study was to analyse the impact of
      organisational characteristics on the turnover intention of care workers working
      at nursing homes in Korea. METHODS: Study participants included 504 care workers
      working at 14 nursing homes in Korea. The variables measured were: high
      performance work practices, consisting of five subfactors (official training,
      employment stability, autonomy, employee participation and group-based payment);
      organisational commitment, consisting of three subfactors (affective, normative
      and continuance commitment); organisational support; and turnover intention. The
      inter-relationship between high-performance work practices, organisational
      support, organisational commitment and turnover intention and the fit of the
      hypothetical model were analysed using structural equation modelling. RESULTS:
      According to our analysis, high-performance work practices not only had a direct
      effect on turnover intention, but also an indirect effect by mediating
      organisational support and commitment. The factor having the largest direct
      influence on turnover intention was organisational commitment. CONCLUSIONS: The
      results of the present study suggest that to improve health conditions for frail
      elderly patients at nursing homes, as well as the efficiency of nursing homes
      through the continuance of nursing service and enhancement of quality of service,
      long-term care facilities should reduce the turnover intention of care workers by
      increasing their organisational commitment by actively implementing high
      performance work practices.

PMID- 24870927
TI  - Low-dose interleukin 2 to reverse alopecia areata.

PMID- 24870929
TI  - (2S,4R)- and (2S,4S)-perfluoro-tert-butyl 4-hydroxyproline: two conformationally
      distinct proline amino acids for sensitive application in 19F NMR.
AB  - (2S,4R)- and (2S,4S)-perfluoro-tert-butyl 4-hydroxyproline were synthesized (as
      Fmoc-, Boc-, and free amino acids) in 2-5 steps. The key step of each synthesis
      was a Mitsunobu reaction with perfluoro-tert-butanol, which incorporated a
      perfluoro-tert-butyl group, with nine chemically equivalent fluorines. Both amino
      acids were incorporated in model alpha-helical and polyproline helix peptides.
      Each amino acid exhibited distinct conformational preferences, with (2S,4R)
      perfluoro-tert-butyl 4-hydroxyproline promoting polyproline helix. Peptides
      containing these amino acids were sensitively detected by (19)F NMR, suggesting
      their use in probes and medicinal chemistry. 

PMID- 24870930
TI  - CUL4A contributes to the biology of basal-like breast tumors through modulation
      of cell growth and antitumor immune response.
AB  - The CUL4A E3 ubiquitin ligase is involved in the regulation of many cellular
      processes and its amplification and/or overexpression has been observed in breast
      cancer. The 13q34 amplification, which is associated with the basal-like breast
      cancer subtype, has been proposed as one of the mechanism behind CUL4A up
      regulation. However, the specific contribution of CUL4A to the biology of basal
      like breast tumors has not yet been elucidated. In this work, by using cellular
      models of basal phenotype, we show the inhibitory effect of CUL4A silencing in
      the proliferation and growth of breast cancer cells both, in vitro and in vivo.
      We also demonstrate the transforming capacity of CUL4A exogenous overexpression
      in the 184B5 human mammary epithelial cells in vitro. Our results suggest a
      synergistic effect between CUL4A high levels and the activation of the RAS
      pathway in the tumorigenesis of basal-like breast cancer tumors. In addition, by
      using a proteomics approach we have defined novel candidate proteins and pathways
      that might mediate the oncogenic effect of CUL4A. In particular, we report a
      putative role of CUL4A in bypassing the immune system in breast cancer through
      the down-regulation of several molecules involved in the immune surveillance.
      These findings provide insight into the oncogenic properties of CUL4A in basal
      like breast cancer and highlight the therapeutic opportunities to target CUL4A. 

PMID- 24870931
TI  - Parenclitic networks: uncovering new functions in biological data.
AB  - We introduce a novel method to represent time independent, scalar data sets as
      complex networks. We apply our method to investigate gene expression in the
      response to osmotic stress of Arabidopsis thaliana. In the proposed network
      representation, the most important genes for the plant response turn out to be
      the nodes with highest centrality in appropriately reconstructed networks. We
      also performed a target experiment, in which the predicted genes were
      artificially induced one by one, and the growth of the corresponding phenotypes
      compared to that of the wild-type. The joint application of the network
      reconstruction method and of the in vivo experiments allowed identifying 15
      previously unknown key genes, and provided models of their mutual relationships.
      This novel representation extends the use of graph theory to data sets hitherto
      considered outside of the realm of its application, vastly simplifying the
      characterization of their underlying structure. 

PMID- 24870932
TI  - Detection of endobronchial intubation by monitoring the CO2 level above the
      endotracheal cuff.
AB  - Early detection of accidental endobronchial intubation (EBI) is still an unsolved
      problem in anesthesia and critical care daily practice. The aim of this study was
      to evaluate the ability of monitoring above cuff CO2 to detect EBI (the working
      hypothesis was that the origin of CO2 is from the unventilated, but still
      perfused, lung). Six goats were intubated under general anesthesia and the ETT
      positioning was verified by a flexible bronchoscope. The AnapnoGuard system,
      already successfully used to detect air leak around the ETT cuff, was used for
      continuous monitoring of above-the-cuff CO2 level. When the ETT distal tip was
      located in the trachea, with an average cuff pressure of 15 mmHg, absence of CO2
      above the cuff was observed. The ETT was then deliberately advanced into one of
      the main bronchi under flexible bronchoscopic vision. In all six cases the
      immediate presence of CO2 above the cuff was identified. Further automatic
      inflation of the cuff, up to a level of 27 mmHg, did not affect the above-the
      cuff measured CO2 level. Withdrawal of the ETT and repositioning of its distal
      tip in mid-trachea caused the disappearance of CO2 above the cuff in a maximum of
      3 min, confirming the absence of air leak and the correct positioning of the ETT.
      Our results suggest that measurement of the above-the-cuff CO2 level could offer
      a reliable, on-line solution for early identification of accidental EBI. Further
      studies are planned to validate the efficacy of the method in a clinical setup. 

PMID- 24870933
TI  - Total and methylmercury in soft tissues of white-tailed eagle (Haliaeetus
      albicilla) and Osprey (Pandion haliaetus) collected in Poland.
AB  - Mercury (Hg) contamination in piscivorous birds, especially methylmercury (MeHg),
      has been drawing much attention worldwide in regard to its bioaccumulation and
      biomagnification in food chains. In this study on Hg in the soft tissues of white
      tailed eagles (n = 22) and ospreys (n = 2) from Poland, total Hg (THg) range was
      0.15-47.6 while MeHg range was 0.11-8.05 mg kg-1 dry weight. In both species,
      median THg and MeHg concentrations were lower in the muscle and brain than in the
      liver and kidney. Median nephric residues were just under 3 and 5 mgTHg kg-1 or
      0.9 and 3.7 mgMeHg kg-1 for white-tailed eagle and osprey, respectively. In
      Norwegian data from the 1970s and in our results, MeHg in the muscle of white
      tailed eagle was ~60 % THg (%MeHg = MeHg/THg * 100), lower than in other
      piscivorous birds. A clear similarity in THg tissue levels was found between
      Polish and German populations of white-tailed eagles.

PMID- 24870934
TI  - Maximizing legacy and impact of primary research: a call for better reporting of
      results.
AB  - Much of the scientific literature in existence today is based on model systems
      and case studies, which help to split research into manageable blocks. The impact
      of this research can be greatly increased in meta-analyses that combine
      individual studies published over time to identify patterns across studies;
      patterns that may go undetected by smaller studies and that may not be the main
      subject of investigation. However, many potentially useful studies fail to
      provide sufficient data (typically means, true sample sizes, and measures of
      variability) to permit meta-analysis. Authors of primary research studies should
      provide these summary statistics as a minimum, and editors should require them to
      do so. By putting policies in place that require these summary statistics to be
      included, or even those that require raw data, editors and authors can maximize
      the legacy and impact of the research they publish beyond that of their initial
      target audience. 

PMID- 24870936
TI  - Racial differences in the prevalence of severe aortic stenosis.
AB  - BACKGROUND: In an era of expanded treatment options for severe aortic stenosis,
      it is important to understand risk factors for the condition. It has been
      suggested that severe aortic stenosis is less common in African Americans, but
      there are limited data from large studies. METHODS AND RESULTS: The Synthetic
      Derivative at Vanderbilt University Medical Center, a database of over 2.1
      million de-identified patient records, was used to identify individuals who had
      undergone echocardiography. The association of race with severe aortic stenosis
      was examined using multivariable logistic regression analyses adjusting for
      conventional risk factors. Of the 272 429 eligible patients (mean age 45 years,
      44% male) with echocardiography, 14% were African American and 82% were
      Caucasian. Severe aortic stenosis was identified in 106 (0.29%) African-American
      patients and 2030 (0.91%) Caucasian patients (crude OR 0.32, 95% CI [0.26,
      0.38]). This difference persisted in multivariable-adjusted analyses (OR 0.41
      [0.33, 0.50], P<0.0001). African-American individuals were also less likely to
      have severe aortic stenosis due to degenerative calcific disease (adjusted OR
      0.47 [0.36, 0.61]) or congenitally bicuspid valve (crude OR 0.13 [0.02, 0.80],
      adjusted OR dependent on age). Referral bias against those with severe valvular
      disease was assessed by comparing the prevalence of severe mitral regurgitation
      in Caucasians and African Americans and no difference was found. CONCLUSIONS:
      These findings suggest that African Americans are at significantly lower risk of
      developing severe aortic stenosis than Caucasians.

PMID- 24870939
TI  - Delay in filling first clopidogrel prescription after coronary stenting is
      associated with an increased risk of death and myocardial infarction.
AB  - BACKGROUND: Patients frequently experience difficulties with medication
      compliance after hospital discharge. We investigated the effect of a delay in
      filling a first clopidogrel prescription after hospital discharge on clinical
      outcomes subsequent to coronary stenting. METHODS AND RESULTS: Hospital
      administrative, community pharmacy, and cardiac revascularization data were
      determined for all patients receiving a coronary stent in British Columbia 2004
      2006 with follow-up out to 2 years. Cox's proportional hazard regression
      analysis, adjusting for baseline demographics and procedural variables, was
      performed to examine the effects of delay in filling a clopidogrel prescription
      after hospital discharge on clinical outcomes.Of 15 629 patients treated with
      coronary stents, 3599 received at least 1 drug-eluting stent (DES), whereas 12
      030 received bare metal stents (BMS) alone. In total, 1064 (30%) and 3758 (31%)
      patients in the DES and BMS groups, respectively, failed to fill a prescription
      within 3 days of discharge (median, 1 day; interquartile range [IQR], 1 to 3).
      After regression analysis, a delay of >3 days was predictive of mortality and
      recurrent myocardial infarction (MI) irrespective of stent type (DES: hazard
      ratio [HR], 2.4; 95% confidence interval [CI], 1.7 to 3.4; and HR, 2.0; 95% CI,
      1.5 to 2.7, respectively, and BMS: HR, 2.2; 95% CI, 1.9 to 2.6; and HR, 1.8; 95%
      CI, 1.5 to 2.1, respectively). This excess hazard was greatest in the 30-day
      period immediately after hospital discharge (mortality: HR, 5.5; 95% CI, 3.5 to
      8.6; and MI: HR, 3.1; 95% CI, 2.4 to 4.0, for all patients). CONCLUSIONS: Delays
      in patients filling their first prescription for clopidogrel after coronary
      stenting are common and associated with adverse clinical outcomes, irrespective
      of stent type. Strategies to reduce delays have the potential to improve clinical
      outcomes.

PMID- 24870940
TI  - Prevalence of anemia among elderly inpatients and its association with
      multidimensional loss of function.
AB  - The purpose of this cross-sectional prospective study was to determine the
      prevalence of anemia among elderly hospitalized patients in Germany and to
      investigate its association with multidimensional loss of function (MLF). One
      hundred participants aged 70 years or older from two distinct wards (50 each from
      an emergency department and a medical ward, respectively) underwent a
      comprehensive geriatric assessment (CGA) consisting of the following six tools:
      Barthel Index, mini-mental state examination, clock-drawing test, timed up and go
      test, Esslinger transfer scale, and Daniels test. MLF as an aggregated outcome
      was diagnosed when three or more tests of the CGA showed an abnormal result.
      Anemia was defined according to WHO criteria as a hemoglobin (Hb) concentration
      of <13 g/dL for men and <12 g/dL for women. The prevalence of anemia was 60 %.
      Overall, 61 % of patients presented with three or more abnormal results in the
      six tests of the CGA and, thus, with MLF. Using logistic regression, we found a
      significant association of both anemia and low Hb concentrations with abnormal
      outcomes in five tests of the CGA and, therefore, with domain-specific deficits
      like mobility limitations, impaired cognition, and dysphagia. Furthermore, being
      anemic increased the odds of featuring MLF more than fourfold. This significant
      relationship persisted after adjustment for various major comorbidities. Both
      anemia and geriatric conditions are common in the hospitalized elderly. Given the
      association of anemia with MLF, Hb level might serve as a useful geriatric
      screening marker to identify frail older people at risk for adverse outcomes.

PMID- 24870941
TI  - Factors predicting haematopoietic recovery in patients undergoing autologous
      transplantation: 11-year experience from a single centre.
AB  - Engraftment outcomes following autologous transplantation correlate poorly to
      infused stem cell number. We evaluated 446 consecutive patients who underwent
      autologous transplantation at our centre between 2001 and 2012. The impact of pre
      transplant and collection factors together with CD34(+) dosing ranges on
      engraftment, hospital length of stay (LOS) and survival endpoints were assessed
      in order to identify factors which might be optimized to improve outcomes for
      patients undergoing autologous transplantation using haemopoietic progenitor
      cells-apheresis (HPC-A). Infused CD34(+) cell dose correlated to platelet but not
      neutrophil recovery. Time to platelet engraftment was significantly delayed in
      those receiving low versus medium or high CD34(+) doses. Non-remission status was
      associated with slower neutrophil and platelet recovery. Increasing neutrophil
      contamination of HPC-A was strongly associated with slower neutrophil recovery
      with infused neutrophil dose/kg recipient body weight >=3 * 10(8)/kg having a
      significant impact on time to neutrophil engraftment (p = 0.001). Higher
      neutrophil doses/kg in HPC-A were associated with days of granulocyte colony
      stimulation factor (G-CSF) use, HPC-A volumes >500 ml and higher NCC in HPC-A.
      High infused neutrophil dose/kg and age >65 years were associated with longer
      hospital LOS (p = 0.002 and 0.011 respectively). Only age, disease and disease
      status predicted disease-free survival (DFS) and overall survival (OS) in our
      cohort (p < 0.005). Non-relapse mortality was not affected by low dose of CD34(+)
      (<2 * 10(6)/kg). In conclusion, our study shows that CD34(+) remains a useful and
      convenient marker for assessing haemotopoietic stem cell content and overall
      engraftment capacity post-transplant. Neutrophil contamination of HPC-A appears
      to be a key factor delaying neutrophil recovery. Steps to minimize the degree of
      neutrophil contamination in HPC-A product may be associated with more rapid
      neutrophil engraftment and reduced hospital LOS.

PMID- 24870937
TI  - Self-rated health predicts healthcare utilization in heart failure.
AB  - BACKGROUND: Heart failure (HF) patients experience impaired functional status,
      diminished quality of life, high utilization of healthcare resources, and poor
      survival. Yet, the identification of patient-centered factors that influence
      prognosis is lacking. METHODS AND RESULTS: We determined the association of 2
      measures of self-rated health with healthcare utilization and skilled nursing
      facility (SNF) admission in a community cohort of 417 HF patients prospectively
      enrolled between October 2007 and December 2010 from Olmsted County, MN. Patients
      completed a 12-item Short Form Health Survey (SF-12). Low self-reported physical
      functioning was defined as a score <= 25 on the SF-12 physical component. The
      first question of the SF-12 was used as a measure of self-rated general health.
      After 2 years, 1033 hospitalizations, 1407 emergency department (ED) visits, and
      19,780 outpatient office visits were observed; 87 patients were admitted to a
      SNF. After adjustment for confounding factors, an increased risk of
      hospitalizations (1.52 [1.17 to 1.99]) and ED visits (1.48 [1.04 to 2.11]) was
      observed for those with low versus moderate-high self-reported physical
      functioning. Patients with poor and fair self-rated general health also
      experienced an increased risk of hospitalizations (poor: 1.73 [1.29 to 2.32];
      fair: 1.46 [1.14 to 1.87]) and ED visits (poor: 1.73 [1.16 to 2.56]; fair: 1.48
      [1.13 to 1.93]) compared with good-excellent self-rated general health. No
      association between self-reported physical functioning or self-rated general
      health with outpatient visits and SNF admission was observed. CONCLUSION: In
      community HF patients, self-reported measures of physical functioning predict
      hospitalizations and ED visits, indicating that these patient-reported measures
      may be useful in risk stratification and management in HF.

PMID- 24870944
TI  - Thermodynamic phase behavior of API/polymer solid dispersions.
AB  - To improve the bioavailability of poorly soluble active pharmaceutical
      ingredients (APIs), these materials are often integrated into a polymer matrix
      that acts as a carrier. The resulting mixture is called a solid dispersion. In
      this work, the phase behaviors of solid dispersions were investigated as a
      function of the API as well as of the type and molecular weight of the carrier
      polymer. Specifically, the solubility of artemisinin and indomethacin was
      measured in different poly(ethylene glycol)s (PEG 400, PEG 6000, and PEG 35000).
      The measured solubility data and the solubility of sulfonamides in
      poly(vinylpyrrolidone) (PVP) K10 and PEG 35000 were modeled using the perturbed
      chain statistical associating fluid theory (PC-SAFT). The results show that PC
      SAFT predictions are in a good accordance with the experimental data, and PC-SAFT
      can be used to predict the whole phase diagram of an API/polymer solid dispersion
      as a function of the kind of API and polymer and of the polymer's molecular
      weight. This remarkably simplifies the screening process for suitable API/polymer
      combinations. 

PMID- 24870943
TI  - Genetic diversity within Mycobacterium tuberculosis complex impacts on the
      accuracy of genotypic pyrazinamide drug-susceptibility assay.

PMID- 24870945
TI  - Development of Frequency of Stools over Time in Children with Hirschsprung
      Disease Posttransanal Endorectal One-Stage Pull-through.
AB  - BACKGROUND: The transanal endorectal one-stage pull-through (TERPT) procedure in
      children with Hirschsprung disease (HD) is frequently used worldwide. To give the
      children's families realistic expectations and to plan the medical care for the
      period after TERPT, the outcome is of great importance. AIM: The aim of this
      article is to collect information on the number of stools passed daily after one
      stage TERPT procedure for HD. Patients and METHODS: A prospective follow-up study
      for collecting information on the outcome of planned TERPT from 2005 through 2012
      was performed. A control group consisting of age and gender matched children was
      used. RESULTS: The results show an initial high frequency of daily stools, median
      12 stools/day (range, 3-30 stools/day), reaching an acceptable situation with
      median 4 stools/day (range, 0-10 stools/day) after 1 year. After 4 years, the
      number of stools did not differ significantly from healthy controls. CONCLUSION:
      This study shows that it takes 4 years after TERPT before the number of stools
      becomes normalized. To compare the long-term outcome, it would be desirable to
      have uniform regular reports on the daily frequency of passed stools,
      incontinence, and constipation during the years after TERPT.

PMID- 24870946
TI  - Effect of Meconium on the Contractility of the Superior Mesenteric Artery: A Clue
      to Intestinal Damage in Gastroschisis.
AB  - INTRODUCTION: Intestinal damage has been shown to occur when intra-amniotic
      meconium concentration exceeds threshold level. However, the mechanism of the
      meconium-induced intestinal damage is still unclear. Intestinal ischemia can
      cause intestinal damage in gastroschisis. This study was aimed to determine the
      effects of intra-amniotic meconium on the contractility of superior mesenteric
      artery (SMA). MATERIALS AND METHODS: Eighteen-day-old fertilized chick embryos
      (Gallus Domesticus) were extirpated and intestines were harvested. The SMA
      specimens were prepared as 4 mm segments in the organ bath with Krebs-Henseleit
      buffer. The isometric contraction responses of the SMA specimens were evaluated
      with norepinephrine, different meconium concentrations, and clear amniotic fluid.
      Maximum isometric contractions responses (MICR) of the SMA specimens were
      recorded with an amplifier system on a computer. RESULTS: In the norepinephrine
      group, MICR was found as 2.92 +/- 0.57 mN. While MICR of the 1/100 meconium group
      (highest meconium concentration) was found as 1.56 +/- 0.40 mN, MICR of the clear
      amniotic fluid group was 0.41 +/- 0.07 mN. The MICR of the norepinephrine group
      was significantly increased compared with the 1/100 meconium and clear amniotic
      fluid groups. MICR of the 1/100 meconium group was also found to be significantly
      increased compared with clear amniotic fluid group. No statistically significant
      difference was found among the meconium subgroups. CONCLUSION: Intra-amniotic
      meconium in fetuses with gastroschisis might cause ischemic intestinal damage by
      reducing the intestinal blood flow. Further studies are needed to show the
      outcomes of the vasoactive effect of meconium on the SMA blood flow.

PMID- 24870947
TI  - Enteric nervous system cell replacement therapy for Hirschsprung disease: beyond
      tissue-engineered intestine.
AB  - Hirschsprung disease (HD), a neurocristopathy characterized by failed migration
      of neural crest cells to the distal colon, requires surgical resection of the
      aganglionic segment. Advances in stem cell and regenerative medicine research
      have opened the possibility to treat HD less invasively using enteric nervous
      system (ENS) cell replacement therapy. This article reviews the progress to date
      of culturing and delivering ENS stem cells in various in vitro and in vivo
      models, as well as review the available evidence of functionality of the
      transplant-derived cells. Potential areas of future study are identified, and
      application of conditions other than HD is briefly discussed. 

PMID- 24870942
TI  - Diffuse large B cell lymphoma: using pathologic and molecular biomarkers to
      define subgroups for novel therapy.
AB  - Diffuse large B cell lymphoma (DLBCL) comprises specific subtypes, disease
      entities, and other not otherwise specified (NOS) lymphomas. This review will
      focus on DLBCL NOS because of their prevalence and their heterogeneity with
      respect to morphology, clinical presentation, biology, and response to treatment.
      Gene expression profiling of DLBCL NOS has identified molecular subgroups that
      correlate with prognosis and may have relevance for treatment based on signaling
      pathways. New technologies have revealed that the "activated B cell" subgroup is
      linked to activation of the nuclear factor kB (NF-kB) pathway, with mutations
      found in CD79A/B, CARD11, and MYD88, and loss of function mutations in TNFAIP3.
      The "germinal center B cell-like" subgroup is linked to mutational changes in
      EZH2 and CREBBP. Biomarkers that are related to pathways promoting tumor cell
      growth and survival in DLBCL have been recognized, although their predictive role
      requires clinical validation. Immunohistochemistry for detecting the expression
      of these biomarkers is a practical technique that could provide a rational for
      clinical trial design.

PMID- 24870948
TI  - Movements of individual digits in bimanual prehension are coupled into a grasping
      component.
AB  - The classic understanding of prehension is that of coordinated reaching and
      grasping. An alternative view is that the grasping in prehension emerges from
      independently controlled individual digit movements (the double-pointing model).
      The current study tested this latter model in bimanual prehension: participants
      had to grasp an object between their two index fingers. Right after the start of
      the movement, the future end position of one of the digits was perturbed. The
      perturbations resulted in expected changes in the kinematics of the perturbed
      digit but also in adjusted kinematics in the unperturbed digit. The latter
      effects showed up when the end position of the right index finger was perturbed,
      but not when the end position of the left index finger was perturbed. Because the
      absence of a coupling between the digits is the core assumption of the double
      pointing model, finding any perturbation effects challenges this account of
      prehension; the double-pointing model predicts that the unperturbed digit would
      be unaffected by the perturbation. The authors conclude that the movement of the
      digits in prehension is coupled into a grasping component. 

PMID- 24870951
TI  - Ordered BaAl4-type variants in the BaAu(x)Sn(4-x) system: a unified view on their
      phase stabilities versus valence electron counts.
AB  - Three ordered structures of the tetragonal BaAl4 type were identified in the Ba
      Au-Sn system, from which a unified view of the interplay between the valence
      electron counts (VECs) and phase stabilities of these three types of derivatives
      can be developed. The BaNiSn3 (I4mm), ThCr2Si2 (I4/mmm), and CaBe2Ge2 (P4/nmm)
      type BaAu(x)Sn(4-x) phases occurred respectively at x = 0.78(1)-1, 1.38(1)
      1.47(1), and 1.52(1)-2.17(1), consistent with theoretical atomic "coloring"
      analyses that reveal an optimal VEC of ~14 for the ThCr2Si2 type but larger and
      smaller values respectively for the BaNiSn3- and CaBe2Ge2-type structures.

PMID- 24870949
TI  - Metabolic health is a more important determinant for diabetes development than
      simple obesity: a 4-year retrospective longitudinal study.
AB  - BACKGROUND: Recent studies report the importance of metabolic health beyond
      obesity. The aim of this study is to compare the risk for diabetes development
      according to different status of metabolic health and obesity over a median
      follow-up of 48.7 months. METHODS: 6,748 non-diabetic subjects (mean age 43
      years) were divided into four groups according to the baseline metabolic health
      and obesity status: metabolically healthy non-obese (MHNO), metabolically healthy
      obese (MHO), metabolically unhealthy non-obese (MUHNO) and metabolically
      unhealthy obese (MUHO). Being metabolically healthy was defined by having less
      than 2 components among the 5 components, that is, high blood pressure, high
      fasting blood glucose, high triglyceride, low high-density lipoprotein
      cholesterol and being in the highest decile of homeostasis model assessment
      insulin resistance (HOMA-IR) index. Obesity status was assessed by body mass
      index (BMI) higher than 25 kg/m2. The development of diabetes was assessed
      annually from self-questionnaire, fasting glucose and HbA1c. RESULTS: At
      baseline, 45.3% of the subjects were MHNO, 11.3% were MHO, 21.7% were MUHNO, and
      21.7% were MUHO. During a median follow-up of 48.7 months, 277 subject (4.1%)
      developed diabetes. The hazard ratio for diabetes development was 1.338 in MHO
      group (95% CI 0.67-2.672), 4.321 in MUHNO group (95% CI 2.702-6.910) and 5.994 in
      MUHO group (95% CI 3.561-10.085) when MHNO group was considered as the reference
      group. These results were similar after adjustment for the changes of the risk
      factors during the follow-up period. CONCLUSION: The risk for future diabetes
      development was higher in metabolically unhealthy subgroups compared with those
      of metabolically healthy subjects regardless of obesity status.

PMID- 24870953
TI  - Degree of value alignment - a grounded theory of rural nurse resignations.
AB  - INTRODUCTION: The shortage of nurses willing to work in rural Australian
      healthcare settings continues to worsen. Australian rural areas have a lower
      retention rate of nurses than metropolitan counterparts, with more remote
      communities experiencing an even higher turnover of nursing staff. When retention
      rates are lower, patient outcomes are known to be poorer. This article reports a
      study that sought to explore the reasons why registered nurses resign from rural
      hospitals in the state of New South Wales, Australia. METHODS: Using grounded
      theory methods, this study explored the reasons why registered nurses resigned
      from New South Wales rural hospitals. Data were collected from 12 participants
      using semi-structured interviews; each participant was a registered nurse who had
      resigned from a rural hospital. Nurses who had resigned due to retirement,
      relocation or maternity leave were excluded. Interviews were transcribed verbatim
      and imported into NVivo software. The constant comparative method of data
      collection and analysis was followed until a core category emerged. RESULTS:
      Nurses resigned from rural hospitals when their personal value of how nursing
      should occur conflicted with the hospital's organisational values driving the
      practice of nursing. These conflicting values led to a change in the degree of
      value alignment between the nurse and hospital. The degree of value alignment
      occurred in three dynamic stages that nurses moved through prior to resigning.
      The first stage, sharing values, was a time when a nurse and a hospital shared
      similar values. The second stage was conceding values where, due to perceived
      changes in a hospital's values, a nurse felt that patient care became compromised
      and this led to a divergence of values. The final stage was resigning, a stage
      where a nurse 'gave up' as they felt that their professional integrity was
      severely compromised. The findings revealed that when a nurse and organisational
      values were not aligned, conflict was created for a nurse about how they could
      perform nursing that aligned with their internalised professional values and
      integrity. Resignation occurred when nurses were unable to realign their personal
      values to changed organisational values - the organisational values changed due
      to rural area health service restructures, centralisation of budgets and
      resources, cumbersome hierarchies and management structures that inhibited
      communication and decision making, out-dated and ineffective operating systems,
      insufficient and inexperienced staff, bullying, and a lack of connectedness and
      shared vision. CONCLUSIONS: To fully comprehend rural nurse resignations, this
      study identified three stages that nurses move through prior to resignation.
      Effective retention strategies for the nursing workforce should address
      contributors to a decrease in value alignment and work towards encouraging the
      coalescence of nurses' and hospitals' values. It is imperative that strategies
      enable nurses to provide high quality patient care and promote a sense of
      connectedness and a shared vision between nurse and hospital. Senior managers
      need to have clear ways to articulate and imbue organisational values and be
      explicit in how these values accommodate nurses' values. Ward-level nurse
      managers have a significant responsibility to ensure that a hospital's values
      (both explicit and implicit) are incorporated into ward culture.

PMID- 24870954
TI  - Personalised external aortic root support.

PMID- 24870950
TI  - Disease control and clinicopathological prognostic factors of total
      pharyngolaryngectomy for hypopharyngeal cancer: a single-center study.
AB  - BACKGROUND: Total pharyngolaryngectomy (TPL) is a conventional and standard
      surgical method for locoregional control of advanced hypopharyngeal cancer (HPC).
      This study aimed to define the clinicopathological prognostic factors of TPL by
      evaluating our surgical experience of TPL in the treatment of HPCs. METHODS: We
      retrospectively reviewed the clinical charts of patients with HPC who were
      treated between 1995 and 2011 at the University of Tokyo Hospital and enrolled
      119 patients who underwent TPL as an initial curative treatment. RESULTS: The
      mean follow-up period was 46 months (range, 2-164 months). The 5-year overall
      survival (OS), disease-specific survival (DSS), locoregional control rates, and
      relapse-free survival for all patients were 44, 53, 76, and 50 %, respectively.
      In multivariate analysis, the number of >=4 metastatic lymph nodes (LNs) was a
      significant poor prognostic factor for both OS and DSS (p = 0.03 and p = 0.01).
      Patients with moderate to severe comorbidities had poor prognoses for OS (p =
      0.002). In addition, patients with the number of >=4 metastatic LNs had a higher
      incidence of distant metastases (p < 0.0001). CONCLUSIONS: The locoregional
      control rate following TPL was acceptable and the number of metastatic LNs was
      associated with the incidence of distant metastases.

PMID- 24870955
TI  - Fluorescence-enabled electrochemical microscopy with dihydroresorufin as a
      fluorogenic indicator.
AB  - Recently, we introduced a new electrochemical imaging technique called
      fluorescence-enabled electrochemical microscopy (FFEM). The central idea of FEEM
      is that a closed bipolar electrode is utilized to electrically couple a redox
      reaction of interest to a complementary fluorogenic reaction converting an
      electrochemical signal into a fluorescent signal. This simple strategy enables
      one to use fluorescence microscopy to observe conventional electrochemical
      processes on very large electrochemical arrays. The initial demonstration of FEEM
      focused on the use of a specific fluorogenic indicator, resazurin, which is
      reduced to generate highly fluorescent resorufin. The use of resazurin has
      enabled the study of analyte oxidation reactions, such as the oxidation of
      dopamine and H2O2. In this report, we extend the capability of FEEM to the study
      of cathodic reactions using a new fluorogenic indicator, dihydroresorufin.
      Dihydroresorufin is a nonfluorescent molecule, which can be electrochemically
      oxidized to generate resorufin. The use of dihydroresorufin has enabled us to
      study a series of reducible analyte species including Fe(CN)6(3-) and
      Ru(NH3)6(3+). Here we demonstrate the correlation between the simultaneously
      recorded fluorescence intensity of resorufin and electrochemical oxidation
      current during potential sweep experiments. FEEM is used to quantitatively detect
      the reduction of ferricyanide down to a concentration of approximately 100 MUM on
      a 25 MUm ultramicroelectrode. We also demonstrate that dihydroresorufin, as a
      fluorogenic indicator, gives an improved temporal response and significantly
      decreases diffusional broadening of the signal in FEEM as compared to resazurin. 

PMID- 24870957
TI  - Identification of the binding site of the quinone-head group in mitochondrial
      Coq10 by photoaffinity labeling.
AB  - Mitochondrial Coq10 is a ubiquinone (UQ)-binding protein that is a member of the
      steroidogenic acute regulatory protein (StAR)-related lipid transfer (START)
      domain superfamily. Deletion of the COQ10 gene was previously shown to cause a
      marked respiratory defect in Saccharomyces cerevisiae and Schizosaccharomyces
      pombe, which indicated that Coq10 may support efficient electron transfer between
      the respiratory complexes; however, its physiological role remains elusive. To
      elucidate the role of Coq10, we attempted to identify the binding site of UQ in
      recombinant S. pombe Coq10 expressed in an Escherichia coli cell membrane through
      photoaffinity labeling with the photoreactive UQ probe, UQ-1, in combination with
      biotinylation of the labeled peptide by means of the so-called click chemistry.
      Comprehensive proteomic analyses revealed that the quinone-head ring of UQ-1
      specifically binds to the N-terminal region of Phe39-Lys45 of Coq10, which
      corresponds to the ligand-binding pocket of many proteins containing the START
      domain. The labeling was completely suppressed in the presence of an excess
      amount of artificial short-chain UQ analogues, such as UQ2. In the Phe39Ala and
      Pro41Ala mutants, the extents of labeling were ~40 and ~60%, respectively, of
      that of wild-type Coq10. While Coq10 has been thought to bind UQ, our work first
      provides the direct evidence of Coq10 accommodating the quinone-head ring of UQ
      in its START domain. On the basis of these results, the physiological role of
      Coq10 has been discussed.

PMID- 24870959
TI  - A systematic review of the effectiveness of interventions to prevent and respond
      to violence against persons with disabilities.
AB  - Persons with disabilities make up some 15% of the world's population and are at
      higher risk of violence. Yet there is currently no systematic review of the
      effectiveness of interventions to prevent violence against them. Thus the aim of
      this review was to systematically search for, appraise the quality of, and
      synthesize the evidence for the effectiveness of interventions to prevent and
      mitigate the consequences of all the main forms of interpersonal violence against
      people with all types of disabilities. The method used consisted of searches of
      eleven electronic databases, hand searches of three journals, scanning of
      reference lists of review articles, contact with experts, appraisal of risk of
      bias using the Quality Assessment Tool for Quantitative Studies, and narrative
      synthesis of results. This resulted in 736 titles being identified, 10 of which
      met the inclusion criteria and 6 and 2 addressed people with intellectual
      disabilities and developmental disabilities, respectively. Only one was from a
      low- and middle-income country. All studies received a weak rating on the quality
      assessment tool and none could be considered effective after taking risk of bias
      into account. In sum, the current evidence base offers little guidance to policy
      makers, program commissioners, and persons with disabilities for selecting
      interventions. More and higher quality research is required, particularly from
      low- and middle-income countries and on other forms of disability such as
      physical impairments, sensory impairments, and mental health conditions. 

PMID- 24870960
TI  - Sexual victimization of youth with a physical disability: an examination of
      prevalence rates, and risk and protective factors.
AB  - Children with disabilities have been shown to be at greater risk of victimization
      than those without. Although much of the research combines disability of any type
      into a single disability category, recent evidence suggests that not all types of
      disabilities are equally associated with victimization. To date, little knowledge
      exists about the victimization of youth with physical disabilities. This study
      used data from a national school-based survey of adolescents (n = 6,749, mean age
      = 15.41, SD = .66) in Switzerland to investigate sexual victimization (SV) among
      physically disabled youth. Two subtypes of SV were differentiated: contact SV,
      including penetration or touching/kissing, and non-contact SV, such as
      exhibitionism, verbal harassment, exposure to sexual acts, or cyber SV. A total
      of 360 (5.1%) youth self-identified as having a physical disability. Lifetime
      prevalence rates for contact SV were 25.95% for girls with a physical disability
      (odds ratio [OR] = 1.29 compared with able-bodied girls), 18.50% for boys with
      physical disability (OR = 2.78 compared with able-bodied boys), and 22.35% for
      the total sample with physical disability (OR = 1.74 compared with able-bodied
      youth). For non-contact SV, the lifetime prevalence was 48.11% for girls with a
      physical disability (OR = 1.44 compared with able-bodied girls), 31.76% for boys
      with physical disability (OR = 1.95 compared with able-bodied boys), and 40.28%
      for the total sample with physical disability (OR = 1.67 compared with able
      bodied youth). After controlling for other risk factors, physical disability was
      a significant predictor of contact and non-contact SV for boys, but not for
      girls. 

PMID- 24870961
TI  - Developing an evidence base for violent and disablist hate crime in Britain:
      findings from the life opportunities survey.
AB  - In the context of there being little robust U.K. data on disabled people's
      exposure to violent crime and hate crime, we examined self-reported rates of
      exposure over the preceding 12 months to violent crime, hate crime, and disablist
      hate crime in a newly established survey, the U.K.'s Life Opportunities Survey.
      Information was collected from a nationally representative sample of 37,513
      British adults (age 16 or older). Results indicated that (a) disabled adults were
      significantly more likely to have been exposed over the previous 12 months to
      violent crime (adjusted odds ratio [OR] = 2.33, 95% confidence interval [CI] =
      [2.08, 2.61]) and hate crime (adjusted OR = 2.58, 95% CI = [2.17, 3.07]) than
      their non-disabled peers, (b) the differential risk of exposure to violent crime
      was particularly elevated among disabled adults with mental health problems
      (adjusted OR = 6.26, 95% CI = [5.01, 7.82]), (c) the differential risk of
      exposure to hate crime was particularly elevated among disabled adults with
      mental health problems (adjusted OR = 10.70, 95% CI = [7.91, 14.47]) or cognitive
      impairments (adjusted OR = 6.66, 95% CI = [3.95, 11.22]), and (d) these effects
      were strongly moderated by poverty status with no increase in differential risk
      of exposure for disabled adults among more wealthy respondents. 

PMID- 24870962
TI  - Gender differences in recurrent mental health contact after a hospitalization for
      interpersonal violence: Western Australia, 1997 to 2008.
AB  - Interpersonal violence and mental illness are significant public health issues.
      This study aimed to determine gender differences in risk factors for recurrent
      mental health contacts after a hospitalization for interpersonal violence in
      Western Australia between 1997 and 2008. This population-based retrospective
      cohort study used linked hospital morbidity data and mental health records to
      identify individuals who were hospitalized due to interpersonal violence and had
      recurrent mental health contacts following hospitalization. A total of 1,969
      individuals had a first-ever mental health contact after their index
      hospitalization for violence. The most common reasons for a mental health contact
      after interpersonal violence hospitalization were anxiety and/or depression (n =
      396, 20.1%), neurotic disorders (n=338, 11.8%), schizophrenia (n=232, 11.8%), and
      psychoactive substance use (n = 206, 10.5%). Different risk factors for recurrent
      contact with mental health services emerged for males and females. For males,
      factors significantly associated with increased risk of recurrent mental health
      contacts included advancing age and not being married. However, for females, type
      of violence, Indigenous status, age, and living in rural or remote areas affected
      the risk of recurrent mental health contacts, whereas marital status did not.
      These findings have implications for the targeting of mental health prevention
      programs tailored specifically for males and females affected by violence. 

PMID- 24870963
TI  - Response to "Acquaintance molestation and youth-serving organizations" by Kenneth
      V. Lanning and Park Dietz.

PMID- 24870964
TI  - Research ethics and private harms.
AB  - This commentary addresses the emotionally powerful account of Nicole Taus
      Kluemper from the perspective of a psychologist familiar with the administrative
      operation of the American Psychological Association (APA) and the ethics of the
      profession. The application of the APA's Ethical Principles of Psychologists and
      Code of Conduct to the case is discussed, and alternative methods of response
      that researchers who have concerns about case studies might use are offered. The
      author concludes that existing ethical principles-the aspirational standards in
      particular-do bear upon the matter in question. However, the enforceable code of
      conduct is not sufficiently clear about obligations to those whom psychologists
      publicly discuss when the psychologist does not have a specific duty of care to
      an individual. 

PMID- 24870965
TI  - Introduction to the series.

PMID- 24870966
TI  - Anesthetic sevoflurane reduces levels of hippocalcin and postsynaptic density
      protein 95.
AB  - Sevoflurane, the commonly used inhalation anesthetic in children, has been shown
      to enhance cytosolic calcium levels and induce cognitive impairment in young
      mice. However, the downstream consequences of the sevoflurane-induced elevation
      in cytosolic calcium levels and the upstream mechanisms of the sevoflurane
      induced cognitive impairment remain largely to be determined. Hippocalcin is one
      of the neuronal calcium sensor proteins, and also binds to postsynaptic density
      protein 95 (PSD-95). We therefore set out to determine the effects of sevoflurane
      on the levels of hippocalcin and PSD-95 in vitro and in vivo. Hippocampus neurons
      from mice and 6-day-old mice were treated with 4.1% sevoflurane for 6 h or 3%
      sevoflurane 2 h daily for 3 days, respectively. We then measured the levels of
      hippocalcin and PSD-95, and assessed whether BAPTA, an intracellular calcium
      chelator, and memantine, a partial antagonist of the NMDA receptor, could inhibit
      the sevoflurane's effects. We found that sevoflurane decreased the levels of
      hippocalcin and PSD-95 in the neurons; and decreased the levels of hippocalcin
      and PSD-95 in the hippocampus of mice immediately after the anesthesia, but only
      the PSD-95 levels three weeks after the anesthesia. BAPTA inhibited the
      sevoflurane's effects in the neurons. Memantine attenuated the sevoflurane
      induced reductions in the levels of hippocalcin and PSD-95, as well as the
      sevoflurane-induced cognitive impairment in mice. These data suggested that
      sevoflurane decreased the levels of hippocalcin and PSD-95, which could serve as
      one of bridge mechanisms between the sevoflurane-induced elevation of cytosolic
      calcium levels and the sevoflurane-induced cognitive impairment.

PMID- 24870967
TI  - Oral administration of the milk casein-derived tripeptide Val-Pro-Pro attenuates
      high-fat diet-induced adipose tissue inflammation in mice.
AB  - Inflammation of adipose tissue triggers the metabolic syndrome, atherosclerosis
      and CHD. In the present study, we investigated whether the milk casein-derived
      tripeptide valine-proline-proline (VPP) has an anti-inflammatory effect on the
      adipose tissue of high-fat diet (HFD)-fed mice. Male C57BL/6J mice (7 weeks of
      age) were fed ad libitum with either a HFD and plain tap water (HFD group) or a
      HFD and water containing 0.3 mg VPP/ml (HFD+VPP group) for 10 weeks. The results
      showed that the expression level of CD18 in the peripheral blood monocytes of the
      HFD+VPP group was significantly decreased compared with the level observed in
      those of the HFD group. Activated monocytes and pro-inflammatory macrophages were
      accumulated in the stromal vascular fractions of the adipose tissue from HFD-fed
      mice, which were significantly decreased in those supplemented with VPP. The
      formation of crown-like structures rich in pro-inflammatory macrophages was also
      significantly reduced in the adipose tissue of mice administered with VPP. Real
      time PCR analysis revealed that the expression of monocyte chemoattractant
      protein-1 and that of the pro-inflammatory cytokine IL-6 in adipose tissue tend
      to be lower in the HFD+VPP group than in the HFD group. These observations
      indicate that oral administration of VPP exerts an anti-inflammatory effect on
      the adipose tissue of HFD-fed mice, which may eventually lead to the primary
      prevention of chronic inflammation-related diseases.

PMID- 24870969
TI  - D-amino acid mediated recruitment of endogenous antibodies to bacterial surfaces.
AB  - The number of antibiotic resistant bacterial strains has been continuously
      increasing over the last few decades. Nontraditional routes to combat bacteria
      may offer an attractive alternative to the ongoing problem of drug discovery in
      this field. Herein, we describe the initial framework toward the development of
      bacterial d-amino acid antibody recruitment therapy (DART). DART represents a
      promising antibiotic strategy by exploiting the promiscuity of bacteria to
      incorporate unnatural d-amino acids and subsequently recruit antibodies to the
      bacterial surface. The conjugation of 2,4-dinitrophenyl (DNP) to various d-amino
      acids led to the discovery of a d-amino acid that specifically tags the surface
      of Bacillus subtilis and Staphylococcus aureus for the recruitment of anti-DNP
      antibodies (a highly abundant antibody in human serum). This system represents a
      novel strategy as an antibacterial therapy that targets planktonic Gram-positive
      bacteria. 

PMID- 24870970
TI  - Graphene quantum dots-band-aids used for wound disinfection.
AB  - Herein, an antibacterial system combining the "safe" carbon nanomaterials,
      graphene quantum dots (GQDs), with a low level of H2O2 has been put forward. It
      has been found that the peroxidase-like activity of GQDs originates from their
      ability to catalyze the decomposition of H2O2, generating .OH. Since the .OH has
      a higher antibacterial activity, the conversion of H2O2 into .OH improves the
      antibacterial performance of H2O2, which makes it possible to avoid the toxicity
      of H2O2 at high levels in wound disinfection. All the experiments in vitro
      display that this intrinsic activity exerts a high enhancement of antibacterial
      activity of H2O2, and the designed system possessed broad spectrum of
      antibacterial activity against both Gram-negative (Escherichia coli) and Gram
      positive (Staphylococcus aureus) bacteria. More importantly, to assess the
      antibacterial efficacy of the designed system in actual wound disinfection, the
      GQD-Band-Aids are prepared and show excellent antibacterial property with the
      assistance of H2O2 at low dose in vivo. 

PMID- 24870968
TI  - The status of radioimmunotherapy in CD20+ non-Hodgkin's lymphoma.
AB  - Rituximab, the CD20-directed antibody, has become a standard component of
      treatment regimens for patients with B cell non-Hodgkin's lymphoma (NHL). The use
      of rituximab has resulted in greatly improved response and survival rates with
      less toxicity relative to standard chemotherapeutic regimes. However, relapse and
      recurrence is common, particularly in indolent varieties which remain incurable,
      requiring alternate therapeutic options. The subsequent coupling of beta-emitting
      isotopes such as (131)I and (90)Y to anti-CD20 monoclonal antibodies (mAbs),
      including rituximab, has been steadily growing over the last decade and
      demonstrates even greater therapeutic efficacy with more durable responses.
      (177)Lutetium-labelled rituximab offers a number of convenient advantages over
      (131)I and (90)Y anti-CD20 mAbs for treatment of NHL, and a number of alpha
      emitting isotopes lie at the frontier of consolidation therapy for residual,
      micrometastatic disease. 

PMID- 24870971
TI  - Physician race and treatment preferences for depression, anxiety, and medically
      unexplained symptoms.
AB  - OBJECTIVES: Studies have repeatedly shown racial and ethnic differences in mental
      health care. Prior research focused on relationships between patient preferences
      and ethnicity, with little attention given to the possible relationship between
      physicians' ethnicity and their treatment recommendations. DESIGN: A
      questionnaire was mailed to a national sample of US primary care physicians and
      psychiatrists. It included vignettes of patients presenting with depression,
      anxiety, and medically unexplained symptoms. Physicians were asked how likely
      they would be to advise medication, see the patient regularly for counseling,
      refer to a psychiatrist, or refer to a psychologist or licensed mental health
      counselor. RESULTS: The response rate was 896 of 1427 (63%) for primary care
      physicians and 312 of 487 (64%) for psychiatrists. Treatment preferences varied
      across diagnoses. Compared to whites (referent), black primary care physicians
      were less likely to use antidepressants (depression vignette), but more likely to
      see the patient for counseling (all vignettes), and to refer to a psychiatrist
      (depression vignette). Asian primary care physicians were more likely to see the
      patient for counseling (anxiety and medically unexplained symptoms vignettes) and
      to refer to a psychiatrist (depression and anxiety vignettes). Asian
      psychiatrists were more likely to recommend seeing the patient regularly for
      counseling (depression vignette). CONCLUSIONS: Overall, these findings suggest
      that physician race and ethnicity contributes to different patterns of treatment
      for basic mental health concerns.

PMID- 24870973
TI  - Two new lignans with antioxidative activities from Jatropha curcas.
AB  - Activity-guided isolation of dried seeds of Jatropha curcas L. led to the
      isolation of two new lignans along with eight known compounds. These compounds
      were determined by spectroscopic analysis to be jatrophasin C (1), jatrophasin D
      (2), beta-sitosterol (3), jatrophasin A (4), daucosterol (5), isoamericanol A
      (6), ( +/- )-3,3'-bisdemethylpinoresinol (7), 7'-epi-sesamin-dicatechol (8),
      isoprincepin (9) and americanol A (10), of which 1 and 2 were new compounds. The
      antioxidative activities along with peroxisome proliferator-activated receptor
      gamma exciting activity of these compounds were also determined. 

PMID- 24870974
TI  - Highlights in metastatic breast cancer from the 2013 San Antonio Breast Cancer
      Symposium (SABCS).

PMID- 24870972
TI  - MicroRNAs in the pathogenesis of myelodysplastic syndromes and myeloid leukaemia.
AB  - PURPOSE OF REVIEW: This review highlights recent insights into the roles of
      microRNAs (miRNAs) in pathogenesis of myeloid malignancies and tantalising
      prospects of miRNA therapy. RECENT FINDINGS: New roles for miRNAs in biological
      and disease processes are constantly being discovered. Although great effort has
      been put into identifying and cataloguing aberrantly expressed miRNAs in
      leukaemia, very little is known about the functional consequences of their
      deregulation in myeloid malignancies. This review will discuss the significance
      of powerful oncogenic miRNAs such as miR-22 in self-renewal and transformation of
      haematopoietic stem cells, as well as their ability to induce epigenetic
      alterations in the pathogenesis of the stem cell disorder myelodysplastic
      syndromes and myeloid leukaemia. SUMMARY: Improved understanding of biological
      roles of miRNAs in the pathogenesis of haematological malignancies will allow
      rational stratification of patients and provide new therapeutic entries for the
      treatment of myelodysplastic syndromes and leukaemia.

PMID- 24870976
TI  - Predicting young adults' intentions to get the H1N1 vaccine: an integrated model.
AB  - Young adults 19 through 24 years of age were among the populations that had the
      highest frequency of infection from the 2009 H1N1 pandemic. However, over the
      2009-2010 flu season, H1N1 vaccine uptake among college students nationwide was
      around 8%. To explore the social cognitive factors that influenced their
      intentions to get the H1N1 vaccine, this study compares the predictive power of
      the theory of planned behavior (TPB), the health belief model (HBM), and an
      integrated model. The final model shows that several HBM variables influenced
      behavioral intentions through the TPB variables. The results suggest that even
      though the TPB seemed a superior model for behavior prediction, the addition of
      the HBM variables could inform future theory development by offering health
      specific constructs that potentially enhance the predictive validity of TPB
      variables. 

PMID- 24870978
TI  - The receptor for advanced glycation end-products (RAGE) plays a key role in the
      formation of nanotubes (NTs) between peritoneal mesothelial cells and in murine
      kidneys.
AB  - The receptor for advanced glycation end-products (RAGE), a multiligand receptor
      of the immunoglobulin superfamily, takes part in various inflammatory processes.
      The role of this receptor in the context of intercellular communication, like
      nanotube (NT)-mediated interaction, is largely unknown. Here, we use cell
      cultures of human and murine peritoneal mesothelial cells as well as murine
      kidneys from wild-type and RAGE knockout mouse models to assess the role of RAGE
      in NT formation and function. We show that loss of RAGE function results in
      reduced NT numbers under physiological conditions and demonstrate the involvement
      of MAP kinase signaling in NT formation. Additionally, we show for the first time
      the existence of NTs in murine kidney tissue and confirm the correlation of RAGE
      expression and NT numbers. Under elevated oxidative stress conditions like renal
      ischemia or peritoneal dialysis, we demonstrate that RAGE absence does not
      prevent NT formation. Rather, increased NT numbers and attenuated kidney tissue
      damage could be observed, indicating that, depending on the predominant
      conditions, RAGE affects NT formation with implications for cellular
      communication. 

PMID- 24870977
TI  - Protein patterns of black fungi under simulated Mars-like conditions.
AB  - Two species of microcolonial fungi - Cryomyces antarcticus and Knufia perforans -
      and a species of black yeasts-Exophiala jeanselmei - were exposed to thermo
      physical Mars-like conditions in the simulation chamber of the German Aerospace
      Center. In this study the alterations at the protein expression level from
      various fungi species under Mars-like conditions were analyzed for the first time
      using 2D gel electrophoresis. Despite of the expectations, the fungi did not
      express any additional proteins under Mars simulation that could be interpreted
      as stress induced HSPs. However, up-regulation of some proteins and significant
      decreasing of protein number were detected within the first 24 hours of the
      treatment. After 4 and 7 days of the experiment protein spot number was increased
      again and the protein patterns resemble the protein patterns of biomass from
      normal conditions. It indicates the recovery of the metabolic activity under
      Martian environmental conditions after one week of exposure.

PMID- 24870979
TI  - Trivalent methylated arsenic metabolites induce apoptosis in human myeloid
      leukemic HL-60 cells through generation of reactive oxygen species.
AB  - Arsenic trioxide (As2O3) has remarkable therapeutic efficacy against leukemia.
      However, after As2O3 biotransformation, the role of arsenic metabolites in the
      clinical efficacy against leukemia still needs to be elucidated. Therefore, to
      explore the contribution of trivalent methylated arsenicals in the therapeutic
      effects, we investigated and compared the effects of arsenite (iAs(III)),
      monomethylarsonous acid (MMA(III)) and dimethylarsinous acid (DMA(III)) on HL-60
      cells. Methylated arsenic species MMA(III) and DMA(III) showed potentially
      reduced cell survival with IC50 values of 3 and 2 MUM, respectively. We found
      that methylated metabolites caused apoptosis through oxidative stress and loss of
      mitochondrial membrane potential. Furthermore, we found that the caspase-9 and -3
      were markedly activated by exposure to methylated metabolites, with cleavage of
      poly-ADP ribose polymerase (PARP). Conversely, cellular apoptosis, generation of
      ROS, activation of caspase-3, -9 as well as PARP cleavage were significantly
      attenuated by pretreatment with an antioxidant, N-acetylcysteine (NAC). DNA
      damage was also markedly observed in HL-60 cells exposed to either MMA(III) or
      DMA(III), while iAs(III) did not show any relevant effects in HL-60 cells.
      Likewise, phosphorylation of the histone H2A variant (gamma-H2AX), a biomarker of
      DNA damage, significantly occurred in cellular nuclei following exposure to two
      methylated species, which was reduced in the presence of NAC, suggesting that the
      induction of DNA damage was predominantly caused by the two metabolites via
      oxidative stress. In conclusion, we suggest that arsenic intermediate
      metabolites; MMA(III) and DMA(III) might prove to be of clinical relevance in
      future as such approaches may help in the treatment of leukemia and other types
      of cancers. 

PMID- 24870980
TI  - A disposable indium-tin-oxide sensor modified by gold nanorod-chitosan
      nanocomposites for the detection of H2O2 in cancer cells.
AB  - Integrating a disposable ITO electrode modified by gold nanorod-chitosan
      nanocomposites, a paper-based electroanalytical device for the real-time
      detection of H2O2 released from cancer cells has been developed. It provided a
      portable platform for biological and biomedical studies dealing with living
      cells. 

PMID- 24870981
TI  - Validation of FLOTAC for the detection and quantification of Troglodytella
      abrassarti and Neobalantidium coli in chimpanzees and pigs.
AB  - We carried out a calibration of FLOTAC for ciliates Troglodytella abrassarti and
      Neobalantidium coli based on the selection of a most appropriate flotation
      solutions, and we also tested its accuracy (i.e., number of detected stages out
      of known added number of stages to fecal samples) and sensitivity for
      trophozoites of both ciliates in chimpanzee feces and N. coli cysts in pig feces,
      compared the detection threshold of FLOTAC with MIF-based sedimentation, and,
      subsequently, tested the losses of ciliate stages during sample preparation. Nine
      flotation solutions were evaluated, and ZnSO4 solution (specific gravity [s.g.]
      1.2) showed to be the most suitable for trophozoite detection, while Sheather's
      solution (s.g. 1.33) was selected as most suitable for cysts. The FLOTAC
      sensitivity in detection of both stages varied: for trophozoites, we found all
      samples were positive when the intensity of infection 10 trophozoites per gram
      and higher, whereas for cysts the sensitivity was lower. The accuracy of FLOTAC
      negatively correlated with infection intensity, and the merthiolate-iodine
      formaldehyde sedimentation-based quantification had a lower detection threshold.
      We demonstrated additional losses of stages of T. abrassarti and N. coli due to
      their retention in the sediment, which is probably a major reason for
      discrepancies in the numbers of countable ciliates between both methods. In
      conclusion, the FLOTAC should not be considered as a gold standard for
      quantification of intestinal ciliates in primates; instead, we recommend the
      modified MIF method. 

PMID- 24870984
TI  - Anatomical location and somatotopic organization of the corticospinal tract in
      the corona radiata of the normal human brain: a diffusion tensor tractography
      study.
AB  - The anatomical location and somatotopic organization of the corticospinal tract
      (CST) in the corona radiata (CR) of the normal human brain have not been studied
      using diffusion tensor tractography so far. In this study, the anatomical
      location and somatotopic organization of the CST in the CR were evaluated by
      determining the highest probabilistic locations and distances between the upper
      and lower extremities in the slices of upper and lower CR in the brain. In the
      mediolateral direction, the average of the highest probabilistic locations for
      the upper and lower extremities were 40.27 and 37.16% at the upper CR level and
      38.19 and 37.14% at the lower CR level, respectively. In the anteroposterior
      direction, the average of the highest probabilistic locations for the upper and
      lower extremities were 62.52 and 75.65% at the upper CR level and 60.19 and
      68.12% at the lower CR level, respectively. The average distances between upper
      and lower extremities for the mediolateral direction were 2.41 mm at the upper CR
      level and 1.21 mm at the lower CR level. The average distances between upper and
      lower extremities for the anteroposterior direction were 5.23 mm at the upper CR
      level and 4.47 mm at the lower CR level, respectively. Our findings suggest that
      the anatomical location and somatotopic organization for the upper extremity are
      located anterolaterally to the lower extremity in the CR of a normal human brain
      and distances between the upper and lower extremities become decreased as the CST
      descends from the upper to the lower CR level. 

PMID- 24870983
TI  - Cultural differences in sensitivity to the relationship between objects and
      contexts: evidence from P3.
AB  - Cross-cultural differences in Easterners and Westerners have been observed in
      different cognitive domains. Differential sensitivity to the relationship between
      objects and contexts might be an underlying cognitive mechanism for these
      differences. Twenty-one Chinese and 22 Germans participated in a three-stimulus
      event-related potential oddball task. They were instructed to monitor geometrical
      forms filled in black (targets) that were presented among a series of blank
      geometrical forms (standards). Novel stimuli were colored images of common
      objects. Robust novelty P3 and target P3 over the entire scalp were observed in
      both groups. As compared with the German group, Chinese participants showed
      larger amplitudes of novelty P3 and target P3 over frontal regions and earlier
      peak latency for target P3. This indicates a higher sensitivity to the
      relationship between contexts and objects in the Chinese as compared with the
      German group, which might be an underlying mechanism for cross-cultural
      differences reported in many cognitive domains. 

PMID- 24870985
TI  - Hyperbaric oxygen preconditioning attenuates postoperative cognitive impairment
      in aged rats.
AB  - Cognitive decline after surgery in the elderly population is a major clinical
      problem with high morbidity. Hyperbaric oxygen (HBO) preconditioning can induce
      significant neuroprotection against acute neurological injury. We hypothesized
      that HBO preconditioning would prevent the development of postoperative cognitive
      impairment. Elderly male rats (20 months old) underwent stabilized tibial
      fracture operation under general anesthesia after HBO preconditioning (once a day
      for 5 days). Separate cohorts of animals were tested for cognitive function with
      fear conditioning and Y-maze tests, or euthanized at different times to assess
      the blood-brain barrier integrity, systemic and hippocampal proinflammatory
      cytokines, and caspase-3 activity. Animals exhibited significant cognitive
      impairment evidenced by a decreased percentage of freezing time and an increased
      number of learning trials on days 1, 3, and 7 after surgery, which were
      significantly prevented by HBO preconditioning. Furthermore, HBO preconditioning
      significantly ameliorated the increase in serum and hippocampal proinflammatory
      cytokines tumor necrosis factor-alpha, interleukin-1 beta (IL-1beta), IL-6, and
      high-mobility group protein 1 in surgery-challenged animals. Moreover, HBO
      preconditioning markedly improved blood-brain barrier integrity and caspase-3
      activity in the hippocampus of surgery-challenged animals. These findings suggest
      that HBO preconditioning could significantly mitigate surgery-induced cognitive
      impairment, which is strongly associated with the reduction of systemic and
      hippocampal proinflammatory cytokines and caspase-3 activity. 

PMID- 24870987
TI  - The relationships between the impact of alcoholic beverage control policies,
      selected contextual determinants, and alcohol drinking in Spain.
AB  - Alcohol prevention policies alone neither cause nor explain changes in alcohol
      consumption, nor in related harm. Alcohol consumption in Spain throughout the
      period 1962-2008 was analyzed considering selected contextual factors and alcohol
      policies. Increased urbanization was found to be associated with higher
      consumption, especially of beer. Restrictive policies regulating purchase age,
      advertising, and licensing premises to sell alcohol were associated with
      decreased alcohol consumption, while lower blood alcohol concentration limits
      were followed by an increase. Study limitations are noted. Changes in the
      evolution of socioeconomic, sociodemographic, and cultural factors should be
      carefully analyzed to inform alcohol policy planning and evaluation. 

PMID- 24870988
TI  - Loricaseius lepontinus gen. nov., sp. nov., a new genus and species of eviphidid
      mite from the Italian Alps (Acari: Mesostigmata), with an updated key to European
      genera of the family Eviphididae.
AB  - A new monotypic genus and a new free-living edaphic species of the family
      Eviphididae, Loricaseius lepontinus gen. nov., sp. nov., are described on the
      basis of adults and deutonymphs collected from litter detritus in the Italian
      Lepontine Alps (Piemonte, Val d'Ossola). The new genus is characterized by a
      widened and truncate idiosomal vertex with widely spaced setae j2, peritrematal
      shields extensively expanded laterally in adult stages, narrowed intercoxal
      region, tarsus I dorsally concave, and strong sexual dimorphism of some secondary
      sexual characters (dorsal sculpture, posteroventral sclerotization of soft
      integument, shape of anal shield, opisthogastric and posterodorsal chaetotaxy).
      Also, the female's anal shield is surrounded by a large area of strongly
      sclerotized skin that resembles a ventri-anal shield, with well-developed
      anterolateral extensions projecting between the dorsal and peritrematal shields,
      and posteriorly and laterally fused with the dorsal shield. We show that this may
      be an unusual type of age-related secondary sclerotization unknown in the family.
      An updated key to European genera of the family is presented. 

PMID- 24870986
TI  - Alcohol consumption and its related harms in The Netherlands since 1960:
      relationships with planned and unplanned factors.
AB  - AIM: to establish which unplanned (social developments) and planned (alcohol
      policy measures) factors are related to per capita consumption and alcohol
      related harms in the Netherlands. METHODS: linear regression was used to
      establish which of the planned and unplanned factors were most strongly connected
      with alcohol consumption and harms. Artificial Neural Analysis (ANN) was used to
      inspect the interconnections between all variables. RESULTS: mothers age at birth
      was most strongly associated with increase in consumption. The ban on selling
      alcoholic beverages at petrol station was associated with a decrease in
      consumption. The linear regression of harms did not show any relation between
      alcohol policy measures and harms. The ANN-analyses indicate a very high
      interconnectedness between all variables allowing no causal inferences.
      Exceptions are the relation between price of beer and wine and the consumption of
      these beverages and the relation between a decrease in transport mortality and
      the increased use of breathalyzers tests and a restriction of paracommercial
      selling. CONCLUSIONS: unplanned factors are most strongly associated with per
      capita consumption and harms. ANN-analysis indicates that price of alcoholic
      beverages, breath testing, and restriction of sales may have had some influence.
      The study's limitations are noted.

PMID- 24870989
TI  - Review of the genus Lasiochira Meyrick, 1931 (Lepidoptera: Oecophoridae).
AB  - The genus Lasiochira Meyrick, 1931 is reviewed, based on the specimens collected
      from China, Korea, and Vietnam. Of the eight species involved in this study, six
      are described as new: L. flavaterminata sp. nov., L. jianfengensis sp. nov., L.
      jiulongshana sp. nov., L. pallidiptera sp. nov., L. rosataenia sp. nov. and L.
      taiwanensis sp. nov. Photographs of adults and genital structures as well as the
      wing venation are provided, along with a key to all the known species. 

PMID- 24870990
TI  - Revision of the Afrotropical species of Gonatopus group 3 (Hymenoptera:
      Dryinidae), with description of a new species from Ghana.
AB  - The Afrotropical species of Gonatopus Ljungh, 1810 group 3 are revised. A new
      species is described from Ghana, Eastern Region: G. schwarzorum Guglielmino &
      Olmi, sp. nov. A new key to the females of the Afrotropical species of Gonatopus
      group 3 is presented. 

PMID- 24870991
TI  - Two new species of Tanaidacea (Crustacea, Peracarida) from Taiwan.
AB  - Two new species, representing the genus Aparatanais of the family Paratanaidae
      and the genus Tanais of the family Tanaidae (both families belonging to the
      suborder Tanaidomorpha), are described in the present study. The genus
      Aparatanais, the family Paratanaidae and the superfamily Paratanaoidea are
      recorded for the first time from Taiwan. Aparatanais lenoprimorum sp. nov.
      departs from its congeners by the lack of subdistal teeth on the superior margin
      of the right mandible and without serration on left mandible lacinia mobilis.
      Tanais nuwalianensis sp. nov. is distinguished from its most similar congener,
      Tanais tinhauae, by the presence of a much smaller right mandible lacinia
      mobilis, fewer carpal spines on pereopods 2-6, fewer leaf-like setae on the
      distal margin of the propodus of Pereopod 6, and fewer inner setae on the pleopod
      basis. Morphological comparisons between members of the genus Aparatanais, as
      well as the genus Tanais are tabulated. 

PMID- 24870992
TI  - To systematics of the genus Saetheria Jackson (Diptera, Chironomidae) from the
      Russian Far East.
AB  - The genus Saetheria Jackson from the Russian Far East is reviewed. The males of
      S. reissi Jackson, 1977, S. tamanipparai (Sasa, 1983) and S. tylus (Townes, 1945)
      are redescribed and figured. The pupa of S. reissi is redescribed and
      illustrated. The larva of S. reissi Jackson is described for the first time.
      Comments on the systematics and distribution of each species are provided.
      Paracladopelma kisopediformis Sasa, Kondo, 1993 is designated a new junior
      synonym of S. reissi Jackson, 1977. Keys to the males, pupae and larvae of the
      Russian Saetheria are given. 

PMID- 24870993
TI  - A new species of Streptocephalus (Crustacea: Anostraca: Streptocephalidae) from
      the Western Ghats, India, with a key to the Asian species.
AB  - We present and describe the fairy shrimp Streptocephalus sahyadriensis sp. nov.
      from the Western Ghats of India. This species is most similar to S. simplex
      Gurney, 1906 and S. dichotomus Baird, 1860 sharing similar basic antennal
      appendage morphology. However, S. sahyadriensis sp. nov. differs in the form of
      the ornamentation on the peduncle and the arrangement and form of spines on the
      antennal appendage. The three species also have different egg surface
      morphologies. The Asian species of Streptocephalus are discussed and a key to
      species is provided. 

PMID- 24870994
TI  - Vanmanenia maculata, a new species of hillstream loach from the Chang-Jiang
      Basin, South China (Teleostei: Gastromyzontidae).
AB  - Vanmanenia maculata, new species, is described from the middle and lower Chang
      Jiang basin in Hubei, Hunan, and Jiangxi provinces, South China. This new
      species, along with V. caldwelli, V. stenosoma, and V. striata, is distinguished
      from all other Chinese species of the genus by lacking secondary rostral barbels.
      It is distinct from V. caldwelli and V. striata in anus placement, rostral lobule
      shape, and body coloration, and from V. stenosoma in having a larger scaleless
      area on the ventral surface of the body and a shallower caudal-peduncle.
      Vanmanenia polylepis should be removed from the synonymy of V. pingchowensis and
      regarded as valid. 

PMID- 24870995
TI  - A new species of Neolebouria Gibson, 1976 (Opecoelidae: Plagioporinae) from the
      whitecheek monocle bream, Scolopsis vosmeri (Perciformes: Nemipteridae), from the
      Panjim coast at Goa, with a checklist of parasites previously reported from this
      fish.
AB  - Neolebouria capoori n. sp. (Opecoelidae: Plagioporinae) is described from the
      whitecheek monocle bream, Scolopsis vosmeri (Bloch) (Perciformes: Nemipteridae)
      from the Panjim coast on the central west coast of India at Goa. The new species
      differs from both Neolebouria cantherhini (Li, Qiu & Zhang, 1988) as originally
      described from Thamnaconus modestus (Gunther) (syn. Cantherines modestus Gunther
      ) and Neolebouria confusum (Overstreet, 1969) as originally described from
      Ocyurus chrysurus (Bloch) by having the cirrus sac surpassing the ventral sucker
      posteriorly in N. cantherhini and being entirely preacetabular in N. confusum
      compared to terminating near the midlevel of the ventral sucker in N. capoori n.
      sp. The new species is most similar to N. confusum, but it further differs from
      this species by having the vitelline fields terminating near the level of the
      esophageal bifurcation compared to terminating near the level of the posterior
      margin of the pharynx, a larger sucker ratio (1:1.7-1:2.0 compared to 1:1.4
      1:1.7), a somewhat shorter cirrus sac relative to body length (160-448,
      representing 9-18% of the body length compared to about 367, representing 22%),
      and the egg of the new species has a boss at the anopercular end that is not
      present in N. confusum. This study represents the first report on an opecoelid
      from S. vosmeri. A review of the parasites reported from S. vosmeri is included. 

PMID- 24870996
TI  - Phenotypic variation and identification of Phenacoccus solenopsis Tinsley
      (Hemiptera: Pseudococcidae) in China.
AB  - Phenacoccus solenopsis Tinsley (Hemiptera: Pseudococcidae) is an invasive
      mealybug that seriously damages cotton and other important crops. In previous
      studies in China, the presence of two submedian longitudinal lines of pigmented
      spots on the dorsum of adult females frequently has been used to identify this
      species. However, the present study records the occasional absence of pigmented
      spots in a sample from Guangxi province, China. Specimens without pigmented spots
      showed all the molecular and morphological characters that separate P. solenopsis
      from the similar species P. solani Ferris, especially the distribution of
      multilocular disc pores. In different geographic populations of P. solenopsis in
      China, mitochondrial COI and nuclear 28SrDNA genes are very similar (99.8-100%),
      indicating that they are conspecific. For COI, the genetic distance between P.
      solenopsis and P. solani is more than 3%. A map of the distribution of P.
      solenopsis in China is given. To help identify both pigmented and non-pigmented
      P. solenopsis accurately, an identification key to the 16 species of Phenacoccus
      found in China is provided. The key also identifies five potentially invasive
      Phenacoccus species not yet established in China, in case they get introduced
      there. 

PMID- 24870997
TI  - Monopelopia mongpuense sp. n., a phytotelmata midge from sub-Himalayan region of
      India (Diptera: Chironomidae: Tanypodinae).
AB  - Immature and adult stages of Monopelopia mongpuense sp. n. from phytotelmata of
      Cedrus deodara (Lamb.) in Darjeeling are described along with biological notes.
      Key to the adult males of all species of the genus Monopelopia Fittkau is also
      presented. This genus is recorded for the first from Indian subcontinent. 

PMID- 24870998
TI  - A review of the genus Paraleptomenes Giordani Soika, 1970 (Hymenoptera: Vespidae:
      Eumeninae: Odynerini) from the Indian subcontinent,with the description of a new
      species from the eastern Himalayas.
AB  - The genus Paraleptomenes Giordani Soika, 1970 is reviewed for the Indian
      subcontinent. A new species Paraleptomenes darugiriensis Kumar, Carpenter &
      Sharma, sp. nov. is described. The male of P. rufoniger Giordani Soika, 1994 is
      described for the first time. The distribution records of P. humbertianus (de
      Saussure, 1867), P. miniatus mephitis (Cameron, 1901), P. miniatus miniatus (de
      Saussure, 1855), and P. rufoniger Giordani Soika, 1994 in the Indian states are
      augmented. A key to species of the Indian subcontinent and a world checklist of
      species are provided. 

PMID- 24870999
TI  - Lissothuria caboblanquensis n. sp., a new species of sea cucumber (Holothuroidea:
      Dendrochirotida: Psolidae) from Costa Rica.
AB  - A new species of sea cucumber of the genus Lissothuria Verrill, 1867 is
      described. Lissothuria caboblanquensis n. sp. was found in the Costa Rican
      Pacific, at 17 m depth. The presence of towers with spiny apex and the elaborated
      shape of the hourglasses in the dorsal body wall, make this species unique among
      the species of this genus. This species is distinctive within the genus. The
      shape of the ossicles shows some similarities with L. nutriens H. L. Clark, 1901
      and L. hancocki (Deichmann, 1941). 

PMID- 24871000
TI  - New species and new records of eunicids (Polychaeta, Eunicidae) from Taiwan.
AB  - Seven species of eunicids were found from rocky intertidal and shallow subtidal
      habitats on the coasts of Taiwan. These polychaetous worms belong to two genera,
      Eunice Cuvier, 1817 and Nicidion Kinberg, 1865. Among them, five species are new
      to science, namely Eunice jihueiensis sp. nov., Eunice reticulata sp. nov.,
      Eunice shihmenensis sp. nov., Eunice taoi sp. nov., and Nicidion megabalanicola
      sp. nov., Eunice annulicirrata Miura, 1986 and Eunice dilatata Grube, 1877, are
      documented for the first time from this geographic region. A key to the genus and
      species of these eunicids is provided. 

PMID- 24871001
TI  - Check-list of Anteoninae R. Perkins, 1912 (Hymenoptera: Dryinidae) of South
      Korea, with description of a new species.
AB  - The subfamily Anteoninae (Hymenoptera: Dryinidae) was represented in South Korea
      by fifteen species belonging to the genus Anteon Jurine, 1807. In this paper,
      further eighteen species belonging to two genera are recognized for the first
      time from South Korea: Anteon worakense Kim & Lee, sp. nov., A. albonigrum Olmi,
      1995; A. autumnale Olmi, 1991; A. devriesi Olmi, 1998; A. exiguum (Haupt, 1941);
      A. gaullei Kieffer, 1905; A. hikense Olmi, 1995; A. ingenuum Olmi, 1984; A.
      japonicum Olmi, 1984; A. metuendum Olmi, 1987; A. nanlingense Xu, Olmi & He,
      2011; A. peterseni Olmi, 1984; A. songyangense Xu, He & Olmi, 1998; A.
      sulawesianum Olmi, 1991; A. wushense Olmi, 1991; A. yuani Xu, He & Olmi, 1998;
      Lonchodryinus infuscatus Xu, Olmi & He, 2009; L. ruficornis (Dalman, 1818). A.
      exiguum (Haupt, 1941) is also recorded from Russian Far East (new record). A
      check-list and a key to South Korean species of Anteoninae are presented. 

PMID- 24871002
TI  - What is Ecdyonurus sumatranus Ulmer, 1939? A contribution to the knowledge of the
      genus Rhithrogena in the Oriental Region (Ephemeroptera, Heptageniidae).
AB  - The species Ecdyonurus sumatranus Ulmer, 1939 was described from Sumatra based on
      a female imago and a single nymph. It was designated as the type-species of the
      genus Ecdyonuroides Dang, 1967, erected because of the peculiar morphology of the
      nymph. This genus was put into synonymy later and the species is currently known
      as Thalerosphyrus sumatranus (Ulmer, 1939). The female imago holotype of
      Ecdyonurus sumatranus Ulmer, 1939 is reinvestigated and revealed to belong to the
      genus Rhithrogena Eaton, 1881. The combination Rhithrogena sumatrana (Ulmer,
      1939) comb. nov. is thus proposed. The nymphs described by Ulmer (1939) from Java
      sub. nom. Rhithrogena parva (?) are associated to this species, and are
      redescribed with new material coming from Java and Lombok. Rhithrogena parva
      (Ulmer, 1912) is redescribed based on the syntype series from Taiwan and male
      genitalia are illustrated for the first time. Supplementary description is
      provided for the nymph of Rh. parva and for the one of Rh. ampla Kang & Yang,
      1994, also from Taiwan. The status of the subgenus Tumungula Zhou & Peters, 2004
      is briefly discussed. The nymph associated by Ulmer (1939) to Ecdyonurus
      sumatranus is renamed Thalerosphyrus lamuriensis sp. nov. The genus Ecdyonuroides
      Dang, 1967 is considered as a synonym of Rhithrogena syn. nov. 

PMID- 24871003
TI  - Trimma irinae, (Pisces; Gobioidei) a new species of gobiid fish from Milne Bay
      Province, Papua New Guinea.
AB  - A new species of Trimma, T. irinae, is described from 65 m off Lawadi, Milne Bay
      Province, Papua New Guinea. This colourful new species has red-orange spots on
      the head and anterior trunk, with a yellow to orange body posteriorly. The first
      dorsal fin has two dark basal spots, and the elongated section of the second
      dorsal spine is bright white to pale blue in life. There are 8-9 scales in the
      predorsal midline, usually cycloid scales present along the upper border of the
      opercle in up to three horizontal rows, no cheek scales, and the middle 9-11 rays
      of the pectoral fin are branched. The fifth pelvic fin ray branches once
      dichotomously and is 52-64% the length of the fourth ray, and the basal membrane
      connecting the inner margins of the fifth pelvic fins rays is less than 15% the
      length of the fifth ray. 

PMID- 24871004
TI  - New Sensiava species (Copepoda: Calanoida: Diaixidae) from the deep South
      Atlantic and first description of the female.
AB  - Females are described for the first time in the genus Sensiava Markhaseva &
      Schulz, 2006, that was known previously only from males. Four species of this
      genus are identified from samples collected in the vicinity of the abyssal sea
      bed. Two species, Sensiava secunda sp. nov. and S. peculiaris sp. nov. are named,
      and two species are not given names due to a poor condition of the examined
      specimens and their incomplete descriptions. Sensiava males have also been found
      in the samples. They share with their male congener Sensiava longiseta Markhaseva
      & Schulz, 2006 a geniculate right antennule, which is a plesiomorphy observed
      only in the benthopelagic Clausocalanoidea Giesbrecht, 1893. A differential
      diagnosis for the genus is given, based on both sexes. Sensiava was previously
      known only from the Antarctic waters between 63-64oS, but its distributional
      range now can be extended significantly further to the north, up to the Equator
      in the South Atlantic. 

PMID- 24871005
TI  - Descriptions of three new species of Cossidae (Lepidoptera) from Vietnam, with an
      updated annotated checklist.
AB  - Forty-two species of Cossidae representing 27 genera are reported for Socialist
      Republic of Vietnam. Three species (Paracossus zyaung Yakovlev sp. nov.,
      Phragmacossia laklong Yakovlev sp. nov., Butaya auko Yakovlev sp. nov.) are
      described as new to science. Five species (Paracossus indradit Yakovlev, 2009, P.
      griseatus Yakovlev, 2009, Aholcocerus ihleorum Yakovlev & Witt, 2009,
      Skeletophyllon puer Yakovlev, 2011, Azygophleps scalaris (Fabricius, 1775) are
      new country records. A brief biogegraphical overview of the Cossidae of Vietnam
      is given. 

PMID- 24871007
TI  - A new giant species of Deltochilum subgenus Deltohyboma (Coleoptera,
      Scarabaeidae, Scarabaeinae) from Colombia, with notes on D. spinipes Paulian,
      1938.
AB  - Deltochilum (Deltohyboma) gigante sp. nov., from Parque Nacional Las Cuevas de
      los Guacharos, Huila, Colombia is described based on differences in external and
      genital morphology. Its diagnostic characters are provided and illustrated.
      Lectotype and paralectotypes for D. spinipes, a close relative to the new
      species, are designated. 

PMID- 24871006
TI  - New species and new records of Tetranychidae (Acarina, Prostigmata) from
      Thailand.
AB  - Sampling efforts conducted in several provinces from Thailand disclosed three new
      species of tetranychid mites. Two of them belong to the genus Tetranychus, namely
      Tetranychus occultaspina sp. nov. and Tetranychus truncatissimus sp. nov. and the
      third species belongs to the genus Schizotetranychus, Schizotetranychus
      krungthepensis sp. nov. They were collected on Ipomoea aquatica, Bambusa
      multiplex and Saccharum officinarum, respectively. New records and new hosts are
      also mentioned.  

PMID- 24871008
TI  - Review of the genera Paulomanus Young, 1952 and Beamerana Young, 1952 (Hemiptera:
      Cicadellidae: Typhlocybinae: Empoascini) with description of a new species from
      Argentina.
AB  - The Neotropical microleafhopper genera Paulomanus and Beamerana are redescribed
      based on study of type material and newly collected specimens. Paulomanus is
      recorded for the first time from Argentina and a new species, P. falciformis n.
      sp., is described. Detailed morphological description and illustration of the new
      species and a key to males of the known species of Paulomanus are provided. A key
      to genera of the New World Empoascini is also provided. 

PMID- 24871009
TI  - A new species Chrysorithrum duda (Lepidoptera: Erebidae) from China.

PMID- 24871010
TI  - An exceptional event during the moulting process of an eutardigrade: two bucco
      pharyngeal apparatuses present.
AB  - A specimen of Diphascon (Diphascon) procerum with two bucco-pharyngeal
      apparatuses (one of which should have been expelled during moulting process) is
      described, and that anomalous condition is discussed. 

PMID- 24871011
TI  - Neotropical region: a shapefile of Morrone's (2014) biogeographical
      regionalisation.

PMID- 24871013
TI  - Revision of Trichiscus benoit, 1956 (Hymenoptera, Bethylidae).
AB  - The species of the Afrotropical genus Trichiscus are revised. Fourteen species
      are recognized, two previously described species, T. wittei Benoit and T.
      suzannae Benoit, and twelve new: T. noorti sp. nov., T. denisi sp. nov., T.
      briani sp. nov., T. copelandi sp. nov., T. mourei sp. nov., T. lynnae sp. nov.,
      T. normani sp. nov., T. luboi sp. nov., T. zuparkoi sp. nov., T. ohli sp. nov.,
      T. camargoi sp. nov. and T. jimi sp. nov.. A key to species is proposed. 

PMID- 24871012
TI  - The identity and genetic characterization of Simulium reptans (Diptera:
      Simuliidae) from central and northern Europe.
AB  - Although Simulium reptans Linnaeus is one of the first two blackfly species ever
      described its identity and taxonomy are still not precisely defined. S. reptans
      and closely related species from central and northern Europe were characterized
      based on genetic variability, haplotype number and haplotype distribution. S.
      galeratum can be considered a synonym of S. reptans, but despite this, two
      distinct species are present in Great Britain and central Europe. The available
      name S. reptantoides Carlsson can be used for the second species; earlier
      reported as S. reptans from Great Britain and central Europe. A total of 80
      mitochondrial cytochrome c oxidase I gene sequences were analyzed: 44 S. reptans,
      36 S. reptantoides; 38 from Great Britain, 19 from Slovakia, 8 from Lithuania, 3
      from Latvia and 12 from Sweden. In 73 individuals a 606 bp section (long
      sequences), and in all 80 individuals a fully overlapping 453 bp section (short
      sequences) were analyzed. Results confirmed that S. reptans and S. reptantoides
      are two genetically isolated species. The variation between these species is
      80.01% of total variation; approximately six times higher than the variation
      among the populations within species. The genetic divergence between species is
      7.02% in long sequences and 7.46% in short ones. The genetic divergence within
      species is 1.18% in S. reptans and 0.83% in S. reptantoides in long sequences,
      and 1.38% and 1.05% in short sequences. Maximum likelihood trees, maximum
      parsimony trees and the haplotype network constructed using TCS showed that each
      species consists of two units, labelled as A and B forms. The distribution of the
      S. reptans forms is not identical-in Slovakia and the Baltic area only S. reptans
      B was found, meanwhile both A and B forms were present in Great Britain and
      Sweden; with the A form clearly dominant. In contrast, both forms of S.
      reptantoides were present in Great Britain and Slovakia, and absent in
      Scandinavia and the Baltic area. Additional studies comprising more individuals
      from larger areas of Europe are required to verify the taxonomic position of
      these species' forms. 

PMID- 24871014
TI  - A new species of the sandperch genus Parapercis from the western Indian Ocean
      (Perciformes: Pinguipedidae).
AB  - Parapercis albiventer sp. nov., a new species of sandperch is described based on
      12 specimens collected from the western Indian Ocean. It can be distinguished
      from congeners by having a bright white ventral surface, without color markings
      on lower fourth of body; dorsal surface of head and body densely covered by small
      brown spots; a row of 10 faint reddish blotches on a paler background, along body
      axis; row of 10 deep reddish blotches, the lower part of each blotch with a solid
      black bar ventrally, below mid-lateral body axis; and combination of following
      characters: no palatine teeth; snout long; eye small; interorbital space broad;
      dorsal-fin rays V, 21; anal-fin rays I, 17; pectoral-fin rays 16-17; pored
      lateral-line scales 55-59; predorsal scales 9 or 10; scales on transverse row
      6/17-21; 3 pairs of canine teeth at front of lower jaw; and vertebrae 10 + 20 =
      30. 

PMID- 24871016
TI  - A new hypogean Trechus Clairville (Coleoptera, Carabidae, Trechini) discovered in
      a non-calcareous Superficial Subterranean Habitat of the Iberian System (Central
      Spain).
AB  - A new hypogean species of Trechus Clairville, Trechus arrecheai sp. nov., is
      described from the Iberian Peninsula. It was captured by subterranean pitfall
      traps in a non-calcareous Superficial Subterranean Habitat from the Moncayo
      Massif (Zaragoza, Spain). Data on the accompanying fauna are provided and the
      biogeographical implications of this discovery are discussed. A synthesis of the
      data about the known distribution of the Trechus angusticollis species group is
      provided. 

PMID- 24871015
TI  - Review of the leafhopper genus Coloana Dworakowska (Hemiptera: Cicadellidae:
      Typhlocybinae: Erythroneurini).
AB  - General characteristics of Coloana Dworakowska and a key to known species of the
      genus are provided. Six new species, Coloana accrescens, C. hainanensis, C.
      latiprocessa, C. orthoprocessa, C. recta and C. sinuata spp. nov. from China and
      Thailand are described and illustrated. C. cinerea Dworakowska is newly recorded
      from China. 

PMID- 24871017
TI  - Review of East Asian Heliosia (Ledidoptera: Erebidae: Arctiinae: Lithosiini)
      species, with description of a new genus.
AB  - Oriental species currently classified in the genus Heliosia Hampson, 1900 but in
      fact belonging to Nudariini are separated into the new genus Paraheliosia gen.
      nov.: Paraheliosia elegans (Reich, 1937) comb. nov. (type species) from South
      East China; P. rufa (Leech, 1890) comb. nov. from North China (nominotypical
      subspecies) and Primorskiy Kray of Russia (P. r. ussuriensis (O. Bang-Haas, 1927)
      comb. nov.); and P. novirufa (Fang, 1992) comb. nov. from Sichuan. Presence of
      two strong apical spines at juxta apex and basal costal valve processes looks to
      be well marked autapomorphic characters of the new genus. Heliosia punctata Fang,
      1992 is transferred into Elachistidae, Aeolanthinae but to unknown genus. 

PMID- 24871018
TI  - Kicking Triturus arntzeni when it's down: large-scale nuclear genetic data
      confirm that newts from the type locality are genetically admixed.
AB  - We collected nuclear DNA data (52 markers) with next-generation sequencing for
      nine Triturus newt specimens, including the holotype and two of the paratypes of
      T. arntzeni, from the type locality at Vrtovac in eastern Serbia. We compare
      these data to a reference set composed of the four crested newt species
      distributed in eastern Serbia namely T. cristatus, T. dobrogicus, T. ivanbureschi
      and T. macedonicus to determine to which of these species the newts from the type
      locality of T. arntzeni should be attributed. The majority of alleles in
      individuals from Vrtovac is derived from T. macedonicus, but a considerable
      number of T. ivanbureschi alleles is also present; alleles typical for T.
      cristatus and T. dobrogicus are found at low frequency. Accordingly, we interpret
      Vrtovac as a T. macedonicus - T. ivanbureschi hybrid population, albeit not
      composed of F1 hybrids but of genetically admixed individuals derived through
      multiple generations of backcrossing. The data support the notion that the name
      T. arntzeni should not be applied to a species newly distinguished in T.
      karelinii sensu lato (to which the name T. ivanbureschi has been given). We
      conclude that because of the hybrid nature of the individuals from Vrtovac, the
      name T. arntzeni should be placed not only in the synonymy of T. macedonicus but
      also in the synonymy of T. ivanbureschi. In this study we demonstrate that next
      generation sequencing can provide high quality data for type material with
      degraded DNA and therefore can play an important role in taxonomy. 

PMID- 24871019
TI  - A new species of the genus Ectagela Schmidt from Iran (Hemiptera, Heteroptera,
      Miridae, Phylinae).
AB  - A new species of the genus Ectagela Schmidt (Phylinae) from Iran, Ectagela
      kermanensis sp. nov. is described and illustrated. The type specimens are
      deposited in the insect collection of the Natural History Museum of University of
      Guilan, Rasht, Iran. 

PMID- 24871020
TI  - Two new species of Ochthebius Leach (Coleoptera: Hydraenidae) from Turkey.
AB  - Two new species of Ochthebius Leach (Coleoptera: Hydraenidae) are described from
      Turkey: O. (s.str.) halophilus (Kirikkale Province) and O. (Asiobates) arator
      (Kutahya and Usak Provinces). The former is the first member of the Ochthebius
      (s.str.) notabilis species group from Turkey, and the latter belongs to the O.
      (Asiobates) bicolon group. Both of the new species are characterized by a
      remarkable aedeagus and are very probably endemic to Turkey. 

PMID- 24871021
TI  - New substitute name for the genus Dayus Steiner & Amaral, 1999 (Annelida:
      Polychaeta: Histriobdellidae).

PMID- 24871022
TI  - The tardigrade fauna of Australian marine caves: with descriptions of nine new
      species of Arthrotardigrada.
AB  - Marine caves are known to support a rich macrofauna; however, few studies have
      focused on meiofauna. Marine cave meiofaunal tardigrades have been reported from
      Japan and the Mediterranean Sea and a preliminary list of species including a
      redescription of Actinarctus neretinus Grimaldi de Zio, D'Addabbo Gallo, Morone
      De Lucia, Vaccarella and Grimaldi, 1982 was reported from Fish Rock Cave and
      Jim's Cave on the coast of Australia. This study is the fourth in a series
      describing the unique meiofauna in two Australian submarine caves located off the
      coast of New South Wales, describing nine new species. Only 67 tardigrades were
      collected from the two caves, yet these contained a high diversity of at least 16
      different species which are quite different in the two caves. The fauna includes
      nine arthrotardigrade genera: Actinarctus, Batillipes, Dipodarctus,
      Halechiniscus, Raiarctus, Styraconyx, Tanarctus, Tholoarctus, and
      Wingstrandarctus. This fauna is different from that reported for the high energy
      beaches along the East Coast of Australia. We describe nine new species
      comprising a single batillipedid and eight halechiniscids: Batillipes solitarius
      nov. sp., Dipodarctus australiensis nov. sp., Dipodarctus susannae nov. sp.,
      Raiarctus jesperi nov. sp., Raiarctus katrinae nov. sp., Tanarctus
      hirsutospinosus nov. sp., Tholoarctus oleseni nov. sp., Wingstrandarctus stinae
      nov. sp. and Wingstrandarctus unsculptus nov. sp. 

PMID- 24871023
TI  - Two new sympatric species of Eusarsiella (Ostracoda: Myodocopida: Sarsiellidae)
      from the Florida Keys with a morphological phylogeny of Sarsiellinae.
AB  - We describe two new sympatric species of Sarsiellidae from coastal Florida, USA:
      Eusarsiella bryanjuarezi sp. nov. and Eusarsiella eli sp. nov. We also present a
      morphological character matrix and maximum likelihood phylogenetic analysis for
      Sarsiellinae based on original species descriptions, representing 139 sarsiellins
      (including E. bryanjuarezi and E. eli). While support values across the phylogeny
      are low, E. bryanjuarezi and E. eli form a sister group pair with 68 % bootstrap
      support. Our phylogeny also showed support for six other sympatric sister-species
      pairs, distributed across Sarsiellinae's range, which may be candidates for the
      study of speciation and niche differentiation. Similar to other analyses of
      myodocopids, our Sarsiellinae phylogeny recovered only three monophyletic genera:
      Anscottiella, Cymbicopia, and Chelicopia, indicating that characters used in
      taxonomy may often be homoplasious. Because of our finding of multiple
      polyphyletic genera, including the two most speciose genera in the subfamily
      (Eusarsiella and Sarsiella, the type genus) Sarsiellinae is a strong candidate
      for taxonomic revision. 

PMID- 24871024
TI  - Mixibius parvus sp. nov. and Diphascon (Diphascon) ziliense sp. nov., two new
      species of Eutardigrada from Sicily.
AB  - Two new species, Mixibius parvus sp. nov. and Diphascon (Diphascon) ziliense sp.
      nov. are described from Sicily. Mixibius parvus sp. nov. has three macroplacoids
      and a microplacoid and differs from M. tibetanus, the only other known species of
      the genus with those characteristics, in having a wrinkled cuticle without true
      small tubercles, a shorter microplacoid, smaller claw pt index values, and in
      lacking a cuticular bar on the first three pairs of the legs.Diphascon
      (Diphascon) ziliense sp. nov. lacks eye spots, has a pharyngeal bulb with two
      macroplacoids and a septulum, and possesses lunules and cuticular bars on the
      legs. It is similar to D. (D.) ramazzottii and D. (D.) procerum but differs from
      them in characters of the cuticular ornamentation and, in addition, from D. (D.)
      ramazzottii in having lunules and slightly longer claws in proportion to the body
      size and to the buccal tube. The new species differs from D. (D.) procerum in
      having stouter claws with a wider common portion and with the main branches
      shorter in proportion to the total length of the respective claws. 

PMID- 24871025
TI  - A revision of the subgenus Pedionis (Pedionis) Hamilton from China, with
      description of two new species (Hemiptera: Cicadellidae).
AB  - Twenty species of the subgenus Pedionis occurring in the Chinese fauna are
      recognized, including two new species, P. aculeata sp. nov., P. papillata sp.
      nov. from Guizhou Prov., China. And, P. nankunshanensis Li, Dai & Li, 2011 is
      here considered as a junior synonym of P. yunnana Zhang & Viraktamath, 2010. A
      key to Chinese species of subgenus Pedionis is also provided as well as a
      checklist. 

PMID- 24871026
TI  - Review of Baeolidia, the largest genus of Aeolidiidae (Mollusca: Nudibranchia),
      with the description of five new species.
AB  - This paper discusses the systematics of the aeolid genus Baeolidia Bergh, 1888.
      To date, this monophyletic genus is the most diverse within Aeolidiidae with
      sixteen valid species. Excluding Baeolidia cryoporos Bouchet, 1977, the genus is
      restricted to the Indo-Pacific and Eastern Pacific. Species of Baeolidia show a
      huge intrageneric variability in several morphological characters. Only oral
      glands, if present, may distinguish Baeolidia from other aeolidiids genera.
      Aeolidiella occidentalis Bergh, 1875, Aeolidiella faustina Bergh, 1900 and
      Spurilla orientalis Bergh, 1905 are transferred to Baeolidia but they are
      considered nomina dubia. Five new species, Baeolidia rieae sp. nov., Baeolidia
      variabilis sp. nov., Baeolidia lunaris sp. nov., Baeolidia gracilis sp. nov. and
      Baeolidia scottjohnsoni sp. nov. are described. 

PMID- 24871027
TI  - A review of the Nearctic Odontomachus (Hymenoptera: Formicidae: Ponerinae) with a
      treatment of the males.
AB  - The ant genus Odontomachus Latreille in the United States is reviewed. Six
      species are treated: O. brunneus (Patton), O. clarus Roger, O. desertorum Wheeler
      stat. nov., O. relictus Deyrup and Cover, O. ruginodis M.R. Smith, and O.
      haematodus (Linnaeus), a new record for North America. The spread of O.
      haematodus is documented, and its identity is clarified. The genus is diagnosed
      for species in the Nearctic region for all castes, and worker- and male-based
      keys are presented. The workers and males of all six species are described and
      figured, including the first male descriptions for O. haematodus and O.
      desertorum. This represents the first study of species-level variation in
      Odontomachus male genitalia, and one of the first of such studies of the
      Ponerinae for any biogeographic region. A discussion of the utility of the male
      sex for Odontomachus taxonomy is provided. 

PMID- 24871028
TI  - Eight new species of Australian stiletto flies in the genus Anabarhynchus
      Macquart (Diptera: Therevidae) from South East Queensland.
AB  - We describe, diagnose and illustrate eight new species in the genus Anabarhynchus
      Macquart, 1848 as follows: Anabarhynchus cretatus sp. n., Anabarhynchus darembal
      sp. n., Anabarhynchus iancommoni sp. n., Anabarhynchus longiseta sp. n.
      Anabarhynchus lyncurium sp. n., Anabarhynchus moretonensis sp. n., Anabarhynchus
      neboensis sp. n. and Anabarhynchus wintertoni sp. n. These represent all new
      species in collections from south east Queensland. These new species bring the
      total number of described Australian species in the genus to 112. 

PMID- 24871029
TI  - The family Hyalidae (Crustacea: Amphipoda: Talitroidea) from Korean waters. 1.
      Genus Ptilohyale Bousfield & Hendrycks, 2002.
AB  - Two species of the genus Ptilohyale were collected from shallow coastal waters of
      Korea. One species is identified as a new species: Ptilohyale brevicrus sp. nov.
      The morphology of gnathopod 2, pereopods, uropods and mandible are the major
      characteristics which differentiate the new species from its congeners. The
      remaining species, P. barbicornis (Hiwatari & Kajihara, 1981) is recorded for the
      first time from Korea. Both species are fully described and illustrated. A key to
      the family Hyalidae and species of Ptilohyale from Korea is also provided. 

PMID- 24871030
TI  - New synonymy in the wheat thrips, Haplothrips tritici (Thysanoptera:
      Phlaeothripidae).

PMID- 24871034
TI  - Highly sensitive fluorescence optode based on polymer inclusion membranes for
      determination of Al(III) ions.
AB  - This paper reports the use of a polymer inclusion membranes (PIMs) for direct
      determination of Al(III) ions in natural water by using a fluorescence based
      optode. The best composition of the PIMs consisted of 60 wt.% (m/m) poly (vinyl
      chloride) (PVC) as the base polymer, 20 wt.% (m/m) triton X-100 as an extractant,
      20 wt.% (m/m) dioctyl phthalate (DOP) as plasticizer and morin as the reagent,
      was used in this study. The inclusion of triton X-100 was used for enhancing the
      sorption of Al(III) ions from liquid phase into the membrane phase, thus
      increasing the optode fluorescence intensity. The optimized optode was
      characterized by a linear calibration curve in the range from 7.41 * 10(-7) to
      1.00 * 10(-4) molL(-1) of Al(III), with a detection limit of 5.19 * 10(-7) molL(
      1). The response of the optode was 4 min and reproducible results were obtained
      for eight different membranes demonstrated good membrane stability. The optode
      was applied to the determination of Al(III) in natural water samples. The result
      obtained is comparable to atomic absorption spectrometry method.

PMID- 24871033
TI  - Wnt/beta-catenin signalling maintains self-renewal and tumourigenicity of head
      and neck squamous cell carcinoma stem-like cells by activating Oct4.
AB  - Accumulating evidence suggests that a distinct subpopulation of cancer stem cells
      (CSCs) is responsible for tumour initiation and progression in head and neck
      squamous cell carcinoma (HNSCC). Wnt/beta-catenin signalling is essential for
      stem cell regulation and tumourigenesis, but its molecular mechanism in HNSCC
      CSCs remains unknown. We investigated whether Wnt/beta-catenin signalling
      regulates self-renewal and tumourigenicity of HNSCC stem-like cells in vitro and
      in vivo. Cytoplasmic/nuclear beta-catenin, a major effector of Wnt/beta-catenin
      signalling, was expressed in a subpopulation of tumour cells in primary HNSCC
      tissue but in none of normal head and neck tissues. Overexpression of beta
      catenin increased proliferation of HNSCC cells and induced dedifferentiation of
      these cells to cells with stem-like features. Knockdown of beta-catenin in HNSCC
      stem-like cells blocked their self-renewal capacity, stemness-associated gene
      expression, chemoresistance, and in vivo tumourigenicity. Furthermore, beta
      catenin directly regulates Oct4 transcription in HNSCC stem-like cells. In
      addition, the effect of shRNA-mediated repression of beta-catenin on CSC traits
      in HNSCC stem-like cells was reversed by overexpression of Oct4. In patients with
      HNSCC, higher levels of both cytoplasmic/nuclear beta-catenin and Oct4 correlated
      with the worst prognosis. These results suggest inhibition of Wnt/beta-catenin
      signalling as a novel therapeutic strategy for targeting HNSCC stem-like cells.

PMID- 24871032
TI  - A phase II study of metronomic paclitaxel/cyclophosphamide/capecitabine followed
      by 5-fluorouracil/epirubicin/cyclophosphamide as preoperative chemotherapy for
      triple-negative or low hormone receptor expressing/HER2-negative primary breast
      cancer.
AB  - PURPOSE: Better treatments for triple-negative breast cancer (TNBC) are needed.
      To address this need, we studied the effects of preoperative metronomic
      paclitaxel/cyclophosphamide/capecitabine (mPCX) followed by 5-fluorouracil
      (FU)/epirubicin/cyclophosphamide (FEC) as preoperative chemotherapy in TNBC
      patients. METHODS: Forty primary TNBC patients received four cycles of metronomic
      paclitaxel (80 mg/m(2) on Days 1, 8, and 15), cyclophosphamide (50 mg/body
      daily), and capecitabine (1,200 mg/m(2) daily), followed by four cycles of 5-FU
      (500 mg/m(2)), epirubicin (100 mg/m(2)), and cyclophosphamide (500 mg/m(2)) every
      3 weeks. The primary end point was the pathological complete response (pCR) rate.
      RESULTS: Forty patients formed the intent-to-treat population. The median dose
      intensities of paclitaxel, cyclophosphamide, and capecitabine were 89.7, 92.1,
      and 89.8%, respectively. Five patients discontinued mPCX and two discontinued
      FEC, primarily because of adverse events, resulting in a per-protocol population
      (PPS) of 33 patients. The pCR (ypT0/Tis ypN0) rate was 47.5% (19/40) in the
      intent-to-treat population and 54.5% (18/33) in the PPS. The clinical response
      rates were 36/40 (90.0%) and 31/33 (93.9%) in the intent-to-treat and PPS,
      respectively. The breast conservation rate was 72.7% (24/33), and 5/13 patients
      underwent partial resection instead of pre-planned total mastectomy. Grade 3-4
      adverse events included neutropenia (35%), leukopenia (25%), and hand-foot
      syndrome (8%). CONCLUSIONS: Metronomic PCX followed by FEC chemotherapy was
      associated with a high pCR rate and low toxicity in TNBC patients. Further
      studies of this regimen in larger numbers of patients are warranted.

PMID- 24871035
TI  - Influence of surface coating on structural and photoluminescent properties of
      CaMoO4:Pr nanoparticles.
AB  - CaMoO4:Pr(core), CaMoO4:Pr@CaMoO4 (core/shell) and CaMoO4:Pr@CaMoO4@SiO2
      (core/shell/shell) nanoparticles were synthesized using polyol method. X-ray
      diffraction (XRD), thermogravimatric analysis (TGA), UV-vis absorption, optical
      band gap energy analysis, Fourier transform infrared (FTIR), FT-Raman and
      photoluminescence (PL) spectroscopy were employed to investigate the structural
      and optical properties of the synthesized core and core/shell nanoparticles. The
      results of the XRD indicate that the obtained core, core/shell and
      core/shell/shell nanoparticles crystallized well at ~150  degrees C in ethylene
      glycol (EG) under urea hydrolysis. The growth of the CaMoO4 and SiO2 shell (~12
      nm) around the CaMoO4:Pr core nanoparticles resulted in an increase of the
      average size of the nanopaticles as well as in a broadening of their size
      distribution. These nanoparticles can be well-dispersed in distilled water to
      form clear colloidal solutions. The photoluminescence spectra of core, core/shell
      and core/shell/shell nanoparticles show the characteristic charge transfer
      emission band of MoO4 (2-) (533 nm) and Pr(3+) 4f(2) -> 4f(2), with multiple
      strong (3)H4 -> (3)P2, (1)D2 -> (3)H4 and (3)P0 -> (3) F2 transitions located at
      ~490, 605 and 652 nm, respectively. The emission intensity of the
      CaMoO4:Pr@CaMoO4 core/shell and CaMoO4:Pr@CaMoO4@SiO2 core/shell/shell
      nanoparticles increased ~4.5 and 1.7 times,respectively, with respect to those of
      CaMoO4:Pr core nanoparticles. This indicates that a significant amount of
      nonradiative centers existing on the surface of CaMoO4:Pr@CaMoO4 core/shell
      nanoparticles can be eliminated by the shielding effect of CaMoO4 shells.

PMID- 24870935
TI  - Severity of cardiovascular disease outcomes among patients with HIV is related to
      markers of inflammation and coagulation.
AB  - BACKGROUND: In the general population, raised levels of inflammatory markers are
      stronger predictors of fatal than nonfatal cardiovascular disease (CVD) events.
      People with HIV have elevated levels of interleukin-6 (IL-6), high-sensitivity C
      reactive protein (hsCRP), and D-dimer; HIV-induced activation of inflammatory and
      coagulation pathways may be responsible for their greater risk of CVD. Whether
      the enhanced inflammation and coagulation associated with HIV is associated with
      more fatal CVD events has not been investigated. METHODS AND RESULTS: Biomarkers
      were measured at baseline for 9764 patients with HIV and no history of CVD. Of
      these patients, we focus on the 288 that experienced either a fatal (n=74) or
      nonfatal (n=214) CVD event over a median of 5 years. Odds ratios (ORs) (fatal
      versus nonfatal CVD) (95% confidence intervals [CIs]) associated with a doubling
      of IL-6, D-dimer, hsCRP, and a 1-unit increase in an IL-6 and D-dimer score,
      measured a median of 2.6 years before the event, were 1.39 (1.07 to 1.79), 1.40
      (1.10 to 1.78), 1.09 (0.93 to 1.28), and 1.51 (1.15 to 1.97), respectively. Of
      the 214 patients with nonfatal CVD, 23 died during follow-up. Hazard ratios (95%
      CI) for all-cause mortality were 1.72 (1.28 to 2.31), 1.73 (1.27 to 2.36), 1.44
      (1.15 to 1.80), and 1.88 (1.39 to 2.55), respectively, for IL-6, D-dimer, hsCRP,
      and the IL-6 and D-dimer score. CONCLUSIONS: Higher IL-6 and D-dimer levels
      reflecting enhanced inflammation and coagulation associated with HIV are
      associated with a greater risk of fatal CVD and a greater risk of death after a
      nonfatal CVD event. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrial.gov
      Unique identifier: SMART: NCT00027352, ESPRIT: NCT00004978, SILCAAT: NCT00013611.

PMID- 24871037
TI  - Insects found in birds' nests from Argentina. Pseudoseisura lophotes Reichenbach,
      1853 and Anumbius annumbi (Vieillot, 1817) (Aves: Furnariidae), hosts of Triatoma
      platensis Neiva, 1913 (Hemiptera: Reduviidae: Triatominae).
AB  - The insect fauna of the nests of Pseudoseisura lophotes (Reichenbach, 1853)
      (Aves: Furnariidae) from Argentina was investigated. A total of 110 species (68
      identified to species, 22 identified to genus, 20 identified to family) in 40
      families of 10 orders of insects was found in these nests. Triatoma platensis
      Neiva, 1913 (Hemiptera: Reduviidae) was found again in nests of P. lophotes,
      corroborating after 73 years the first observations made by Mazza in 1936. The
      occurrence of the insects in nests of P. lophotes is compared with the previously
      known insect fauna in nests of A. annumbi, Furnarius rufus (Furnariidae), and
      Myiopsitta monachus (Psittacidae). The insect fauna in additional nests of
      Anumbius annumbi from the same and/or different localities is given, and used in
      comparisons. The first occurrence of Cuterebridae (Diptera) in birds' nests,
      their pupae as the overwintering stage, and the second simultaneous infestation
      by two species of Philornis (Diptera: Muscidae) on the same nestlings are
      presented. Other simultaneous infestations of different hematophagous arthropods
      (Hemiptera: Cimidae; Reduviidae: Triatominae, and Acari: Argasidae) are remarked
      and discussed.

PMID- 24871038
TI  - Names for Ixodidae (Acari: Ixodoidea): valid, synonyms, incertae sedis, nomina
      dubia, nomina nuda, lapsus, incorrect and suppressed names--with notes on
      confusions and misidentifications.
AB  - A major, but not exhaustive, literature revision has been made to compile the
      names of Ixodidae from Linnaeus to present. Names are classified as valid,
      synonyms, lapsus, incertae sedis, nomina dubia, nomina nuda, incorrect and
      suppressed. Notes are included fo<a href="http://dx.doi.org/10.1007/s11250-012
      0218-x">r </a>confusions and misidentifications among different tick species. The
      lists included in this study are neither aimed to be consensual nor focusing to
      stabilize nomenclature, but rather part of a discussion on the species forming
      Ixodidae and a potential aid for research on tick taxonomy and phylogeny. 

PMID- 24871036
TI  - 4-aminoquinolone piperidine amides: noncovalent inhibitors of DprE1 with long
      residence time and potent antimycobacterial activity.
AB  - 4-Aminoquinolone piperidine amides (AQs) were identified as a novel scaffold
      starting from a whole cell screen, with potent cidality on Mycobacterium
      tuberculosis (Mtb). Evaluation of the minimum inhibitory concentrations, followed
      by whole genome sequencing of mutants raised against AQs, identified
      decaprenylphosphoryl-beta-d-ribose 2'-epimerase (DprE1) as the primary target
      responsible for the antitubercular activity. Mass spectrometry and enzyme kinetic
      studies indicated that AQs are noncovalent, reversible inhibitors of DprE1 with
      slow on rates and long residence times of ~100 min on the enzyme. In general, AQs
      have excellent leadlike properties and good in vitro secondary pharmacology
      profile. Although the scaffold started off as a single active compound with
      moderate potency from the whole cell screen, structure-activity relationship
      optimization of the scaffold led to compounds with potent DprE1 inhibition (IC50
      < 10 nM) along with potent cellular activity (MIC = 60 nM) against Mtb.

PMID- 24871040
TI  - Correlation of intercalation potential with d-electron configurations for cathode
      compounds of lithium-ion batteries.
AB  - The d-electron localization is widely recognized as important to transport
      properties of transition metal compounds, but its role in the energy conversion
      of intercalation reactions of cathode compounds is still not fully explored. In
      this work, the correlation of intercalation potential with electron affinity, a
      key energy term controlling electron intercalation, then with d-electron
      configuration, is investigated. Firstly, we find that the change of the
      intercalation potential with respect to the transition metal cations within the
      same structure class is correlated in an approximately mirror relationship with
      the electron affinity, based on first-principles calculations on three typical
      categories of cathode compounds including layered oxides and polyoxyanions Then,
      by using a new model Hamiltonian based on the crystal-field theory, we reveal
      that the evolution is governed by the combination of the crystal-field splitting
      and the on-site d-d exchange interactions. Further, we show that the charge order
      in solid-solution composites and the compatibility of multi-electron redox steps
      could be inferred from the energy terms with the d-electron configuration
      alternations. These findings may be applied to rationally designing new chemistry
      for the lithium-ion batteries and other metal-ion batteries. 

PMID- 24871042
TI  - Proteoglycans, key regulators of cell-matrix dynamics.
AB  - In this special issue of Matrix Biology centered on proteoglycan biology we have
      assembled a blend of articles focused on the state-of-the-art of
      proteoglycanology. The field has greatly expanded in the past three decades and
      now encompasses all the areas of biology. This special issue is divided into five
      chapters describing hyaluronan metabolism, biosynthetic and catabolic pathways of
      proteoglycans and their roles in inflammation, cancer, repair and development. We
      hope that the new original work and the reviews from recognized leaders will
      stimulate investigations in this exciting and fertile field of research. 

PMID- 24871039
TI  - Pharmacokinetic drug interactions between apigenin, rutin and paclitaxel mediated
      by P-glycoprotein in rats.
AB  - The aim of present study was to investigate the effects of apigenin and rutin on
      the pharmacokinetics of paclitaxel after oral administration of paclitaxel with
      apigenin and rutin to rats. Paclitaxel (40 mg/kg) was administered orally alone
      and in combination with apigenin and rutin (10, 20, and 40 mg/kg) for 15
      consecutive days. In the single-dose pharmacokinetic study (SDS), blood samples
      were collected on 1st day whereas on 15th day in the multiple-dose
      pharmacokinetic study (MDS). The plasma concentrations of paclitaxel were
      increased dose-dependently in the combination of apigenin and rutin compared to
      that of paclitaxel control in SDS and MDS (p < 0.01). The areas under the plasma
      concentration-time curve (AUC) and the plasma peak concentrations (C max) of
      paclitaxel with apigenin and rutin were significantly higher (p < 0.01) than that
      of the control. The AUCs and C max of paclitaxel were increased with apigenin and
      rutin in the dose-dependent manner. The half-life (t 1/2) was significantly
      longer than that of the control. Non-everted sacs were filled with paclitaxel 100
      MUM in the presence and absence of verapamil (50 MUM), apigenin, and rutin (50,
      100 MUM) and incubated at 37 oC for 60 min. The absorption of paclitaxel was
      increased in the presence of apigenin, rutin, and verapamil, a typical P
      glycoprotein and Cyp3A4 inhibitor. If these results are confirmed in humans in a
      clinical setting, the paclitaxel dose should be adjusted when it is given
      concomitantly with apigenin and rutin.

PMID- 24871043
TI  - Prevalence of N-methyl-D-aspartate receptor autoantibodies in the peripheral
      blood: healthy control samples revisited.

PMID- 24871041
TI  - Direct observation of the three regions in alpha-synuclein that determine its
      membrane-bound behaviour.
AB  - alpha-synuclein (alphaS) is a protein involved in neurotransmitter release in
      presynaptic terminals, and whose aberrant aggregation is associated with
      Parkinson's disease. In dopaminergic neurons, alphaS exists in a tightly
      regulated equilibrium between water-soluble and membrane-associated forms. Here
      we use a combination of solid-state and solution NMR spectroscopy to characterize
      the conformations of alphaS bound to lipid membranes mimicking the composition
      and physical properties of synaptic vesicles. The study shows three alphaS
      regions possessing distinct structural and dynamical properties, including an N
      terminal helical segment having a role of membrane anchor, an unstructured C
      terminal region that is weakly associated with the membrane and a central region
      acting as a sensor of the lipid properties and determining the affinity of alphaS
      membrane binding. Taken together, our data define the nature of the interactions
      of alphaS with biological membranes and provide insights into their roles in the
      function of this protein and in the molecular processes leading to its
      aggregation. 

PMID- 24871044
TI  - Protective effect of chinonin in MPTP-induced C57BL/6 mouse model of Parkinson's
      disease.
AB  - The aims of this study were to investigate the effect of chinonin in preventing 1
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurodegeneration in
      C57BL/6 mice and to examine the possible mechanisms. The neurotoxin MPTP was
      employed to create a subacute Parkinson's disease (PD)-like model in C57BL/6
      mice. Chinonin (10, 20, 40 mg/kg body weight) was intraperitoneally administered
      0.5 h after MPTP (30 mg/kg) injection for 7 d consecutively. Chinonin showed
      neuroprotective effects in the MPTP-treated mice PD model by ameliorating motor
      impairment in the catwalk and open-field tests. Consistently, chinonin reduced
      loss of dopaminergic neurons in the substantia nigra and prevented depletion of
      dopamine and its metabolites 3-methoxy-4-hydroxy-phenylacetic acid and
      homovanillic acid in the striatum of mice. Compared with the MPTP group, in the
      chinonin plus MPTP groups significant increases of superoxide dismutase activity
      and glutathione levels were observed as well as a distinct reduction of lipid
      peroxidation product malondialdehyde in the striatum. Taken together, we propose
      that chinonin exerts neuroprotective effects in C57BL/6 mouse model of PD and
      these effects may be due to chinonin's antioxidative property.

PMID- 24871045
TI  - ACE in the hole.

PMID- 24871047
TI  - A Raman spectroscopic study of the carbon deposition mechanism on Ni/CGO
      electrodes during CO/CO2 electrolysis.
AB  - In situ and ex situ Raman analyses of porous Ni/CGO electrodes reveal differences
      in the amount, location and type of carbon formed during CO/CO2 electrolysis. The
      results demonstrate the limitations of optical in situ techniques applied to
      Solid Oxide Cells (SOCs) operated in electrolysis conditions. Increased carbon
      deposition close to the electrode-electrolyte interface is likely to be the
      result of high charge-transfer current in that area. The positive effect of a CGO
      interlayer on reducing carbon formation on the fuel electrode is demonstrated. 

PMID- 24871048
TI  - Hematite concave nanocubes and their superior catalytic activity for low
      temperature CO oxidation.
AB  - Hematite (alpha-Fe2O3) concave nanocubes bound by high-index {1344} and {1238}
      facets were synthesized and their catalytic activity for CO oxidation were also
      investigated.

PMID- 24871052
TI  - Near-infrared luminescent PMMA-supported metallopolymers based on Zn-Nd Schiff
      base complexes.
AB  - On the basis of self-assembly from the divinylphenyl-modified Salen-type Schiff
      base ligands H2L(1) (N,N'-bis(5-(3'-vinylphenyl)-3-methoxy-salicylidene)ethylene
      1,2-diamine) or H2L(2) (N,N'-bis(5-(3'-vinylphenyl)-3-methoxy
      salicylidene)phenylene-1,2-diamine) with Zn(OAc)2.2H2O and Ln(NO3)3.6H2O in the
      presence of pyridine (Py), two series of heterobinuclear Zn-Ln complexes
      [Zn(L(n))(Py)Ln(NO3)3] (n = 1, Ln = La, 1; Ln = Nd, 2; or Ln = Gd, 3 and n = 2,
      Ln = La, 4; Ln = Nd, 5; or Ln = Gd, 6) are obtained, respectively. Further,
      through the physical doping and the controlled copolymerization with methyl
      methacrylate (MMA), two kinds of PMMA-supported hybrid materials, doped
      PMMA/[Zn(L(n))(Py)Ln(NO3)3] and Wolf Type II Zn(2+)-Ln(3+)-containing
      metallopolymers Poly(MMA-co-[Zn(L(n))(Py)Ln(NO3)3]), are obtained, respectively.
      The result of their solid photophysical properties shows the strong and
      characteristic near-infrared (NIR) luminescent Nd(3+)-centered emissions for both
      PMMA/[Zn(L(n))(Py)Nd(NO3)3] and Poly(MMA-co-[Zn(L(n))(Py)Nd(NO3)3]), where
      ethylene-linked hybrid materials endow relatively higher intrinsic quantum yields
      due to the sensitization from both (1)LC and (3)LC of the chromorphore than those
      from only (1)LC in phenylene-linked hybrid materials, and the concentration self
      quenching of Nd(3+)-based NIR luminescence could be effectively prevented for the
      copolymerized hybrid materials in comparison with the doped hybrid materials. 

PMID- 24871049
TI  - Development of nutrition standards and therapeutic diet specifications for public
      hospitals in New South Wales.
AB  - In New South Wales (NSW), a new suite of nutrition standards for menus and
      specifications for therapeutic diets to be used in hospitals has been developed.
      These standards were required to facilitate centralised menu planning and food
      production, with the move to management of most hospital food services by
      HealthShare NSW, a state-wide business unit of NSW Health. The standards also aim
      to improve communication between health professionals, particularly with the
      increasing use of computerised meal-ordering systems. Nutrition standards have
      been developed for adult, paediatric and mental health inpatients, and
      specifications for 147 different adult and paediatric therapeutic diets. There is
      still significant variation in the nutrition standards for nutrition and
      therapeutic diets in hospitals across the Australian states, and a move to a more
      nationally harmonised approach would be welcome. Further research is required to
      examine the impact of these standards on operating efficiency and patient care
      outcomes. 

PMID- 24871046
TI  - TRPV1, TRPA1, and TRPM8 channels in inflammation, energy redirection, and water
      retention: role in chronic inflammatory diseases with an evolutionary
      perspective.
AB  - Chronic inflammatory diseases are accompanied by a systemic response of the body,
      necessary to redirect energy-rich fuels to the activated immune system and to
      induce volume expansion. The systemic response is switched on by two major
      pathways: (a) circulating cytokines enter the brain, and (b) signals via sensory
      nerve fibers are transmitted to the brain. Concerning item b, sensory nerve
      terminals are equipped with a multitude of receptors that sense temperature,
      inflammation, osmolality, and pain. Thus, they can be important to inform the
      brain about peripheral inflammation. Central to these sensory modalities are
      transient receptor potential channels (TRP channels) on sensory nerve endings.
      For example, TRP vanilloid 1 (TRPV1) can be activated by heat, inflammatory
      factors (e.g., protons, bradykinin, anandamide), hyperosmolality, pungent
      irritants, and others. TRP channels are multimodal switches that transmit
      peripheral signals to the brain, thereby inducing a systemic response. It is
      demonstrated how and why these TRP channels (TRPV1, TRP ankyrin type 1 (TRPA1),
      and TRP melastatin type 8 (TRPM8)) are important to start up a systemic response
      of energy expenditure, energy allocation, and water retention and how this is
      linked to a continuously activated immune system in chronic inflammatory
      diseases. 

PMID- 24871055
TI  - The demise of the minimum database.

PMID- 24871056
TI  - What is your diagnosis? Fungal osteomyelitis.

PMID- 24871057
TI  - What is your neurologic diagnosis? Vestibular disease.

PMID- 24871058
TI  - Diagnostic imaging in veterinary dental practice. Class II periodontic-endodontic
      lesion.

PMID- 24871059
TI  - ECG of the Month. Isorhythmic atrioventricular dissociation during hypothermia.

PMID- 24871061
TI  - Pathology in practice. Hepatic and splenic myelocytomatosis in an eastern screech
      owl.

PMID- 24871060
TI  - Pathology in practice. Necrotizing fasciitis, osteomyelitis, and streptococcal
      septicemia in a dog.

PMID- 24871062
TI  - Trends in veterinary medical board state disciplinary actions, 2005-2011.

PMID- 24871064
TI  - Comparison of the nutrient composition of commercial dog milk replacers with that
      of dog milk.
AB  - OBJECTIVE: To compare the nutrient composition of commercially available dog milk
      replacers with that of dog milk. DESIGN: Prospective, cross-sectional study.
      SAMPLE: 5 dog milk samples and 15 samples of commercial dog milk replacers.
      PROCEDURES: Dog milk and milk replacers were analyzed for concentrations of total
      protein, essential amino acids, sugars, total fat, essential fatty acids,
      calcium, and phosphorus. Energy density was calculated. Results from milk
      replacers were compared with the range of the concentration of each nutrient in
      milk samples from mature dogs as well as the National Research Council (NRC)
      recommendations for puppy growth. RESULTS: Milk replacers varied widely in
      caloric density and concentration of nutrients such as calcium, protein, and fat.
      Calcium concentration was lower in 14 of 15 milk replacers than in the dog milk
      samples. Docosahexaenoic acid was undetectable in 12 of 15 milk replacers but
      present in all dog milk samples. All milk replacers had numerous essential
      nutrients outside of the range of the dog milk samples, and many had
      concentrations of amino acids, essential fatty acids, calcium, and phosphorus
      less than the NRC minimal requirement or recommended allowance. Compared with NRC
      recommendations, some dog milk samples had concentrations of total protein,
      linoleic acid, calcium, or phosphorus less than the recommended allowance.
      CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that there was substantial
      variation in nutrient composition of 15 dog milk replacers and that some products
      were closer approximations of dog milk than others. Nearly all products would
      benefit from more appropriate calcium, amino acids, and essential fatty acids
      concentrations and better feeding directions.

PMID- 24871065
TI  - In vitro evaluation of three intravenous fluid line warmers.
AB  - OBJECTIVE: To determine in vitro output temperature differences of 3 IV fluid
      warmers. DESIGN: Prospective, randomized study. SAMPLE: 3 IV fluid warmers.
      PROCEDURES: Warming capabilities of a distance-dependent blood and fluid warmer
      marketed for human and veterinary use (product A) and a veterinary-specific
      distance-dependent fluid warmer (product B) were compared at 0, 4, 8, and 12 cm
      from the device to the test vein and at flow rates of 20, 60, 100, 140, 180, 220,
      260, and 300 mL/h with room temperature (approx 22 degrees C) fluids (phase 1).
      The superior warming device was compared against a distance-independent IV fluid
      warmer (product C) with room temperature fluids at the same flow rates (phase 2).
      The effect of prewarmed fluids (38 degrees C) versus room temperature fluids was
      evaluated with the superior warming device from phase 2 (phase 3). RESULTS: In
      phase 1, product B produced significantly warmer fluids than product A for all
      flow rates and distances. Both distance-dependent devices produced warmer fluid
      at 0 cm, compared with 4, 8, and 12 cm. In phase 2, product B produced warmer
      fluid than product C at 60, 100, 140, and 180 mL/h. In phase 3, there was no
      significant benefit to use of prewarmed fluids versus room temperature fluids.
      Output temperatures >= 36.4 degrees C were achieved for all rates >= 60 mL/h.
      CONCLUSIONS AND CLINICAL RELEVANCE: Product B had superior warming capabilities.
      Placing the fluid warmer close to the patient is recommended. Use of prewarmed
      fluids had no benefit. Lower IV fluid flow rates resulted in lower output fluid
      temperatures.

PMID- 24871067
TI  - Endoscopic mucosal resection and snare polypectomy for treatment of a colorectal
      polypoid adenoma in a dog.
AB  - CASE DESCRIPTION: An 11-year-old castrated male mixed-breed dog was examined for
      a 3-month history of hematochezia and tenesmus. Abdominal ultrasonography and
      rectal examination prior to referral had revealed a colorectal polyp, diagnosed
      as a benign colorectal polypoid adenoma after histologic examination of tissue
      samples. The patient was referred for treatment. CLINICAL FINDINGS: A 2-cm
      diameter sessile polypoid mass was located approximately 6 cm orad to the anus in
      the right dorsolateral region of the descending colon just caudal to the pubis.
      There was no evidence of metastasis on thoracic radiography or abdominal
      ultrasonography. Results of a CBC and serum biochemical analysis were within
      reference limits. TREATMENT AND OUTCOME: Endoscopic mucosal resection (EMR) and
      snare electrocautery were used to resect the mass and a definitive
      histopathologic diagnosis of a sessile colorectal polypoid adenoma was made. A
      9.9-mm gastroduodenoscope was used during colonoscopy to inspect the mass. To aid
      in EMR, a 25-gauge endoscopic injection needle was used to infuse sterile saline
      (0.9% NaCl) solution under the base of the polyp, into the submucosa to elevate
      the mucosa from the muscularis layer beneath the polyp prior to polypectomy. This
      was necessary because of the sessile, rather than pedunculated, base of the mass.
      The entire polyp was successfully removed with endoscopic guidance. The clinical
      signs of hematochezia and tenesmus resolved immediately, and serial rectal
      examinations were performed over the following 36 months with no palpable
      evidence of recurrence. CLINICAL RELEVANCE: The patient described in the present
      report underwent successful colonic EMR and snare polypectomy with no known
      evidence of mass recurrence during the following 36 months, suggesting that this
      minimally invasive procedure may be a valuable treatment option for sessile
      polyps. The advantage of this technique was that elevation of the mucosa via
      injection of saline solution improved visibility of the polyp and helped to
      separate the polyp base from the deeper submucosal colorectal tissue, making
      complete resection possible.

PMID- 24871066
TI  - Cutaneous lymphoma of the tarsus in cats: 23 cases (2000-2012).
AB  - OBJECTIVE: To determine features of lymphoma of the tarsus in cats. DESIGN: Multi
      institutional retrospective study. ANIMALS: 23 cats with cutaneous lymphoma of
      the tarsus. PROCEDURES: Veterinary oncologists were requested to submit cases
      fitting the following criteria: histologically or cytologically confirmed
      lymphoma with a location at or near the tarsus and described as subcutaneous or
      mass-like. Data regarding breed, sex, age, FeLV and FIV status, and reason for
      evaluation were collected. Results of staging tests, location of the tumor,
      immunophenotype, and histopathologic description were recorded. Type of
      treatments, outcome, survival time, presence or absence of progressive disease,
      and cause of death or reason for euthanasia were also recorded. RESULTS: Most
      cats were older, with a median age of 12 years (range, 7 to 18 years). No
      association with positive retroviral status was found. Popliteal lymph node
      involvement at diagnosis was reported in 5 cats, and a suspicion of lymphoma at a
      different site on the basis of results of abdominal ultrasonography was reported
      in 4 cats. Treatments were variable and included corticosteroids alone (n = 2),
      chemotherapy (9), radiation and chemotherapy (7), or surgery with or without
      chemotherapy (5). Thirteen cats were reported to have lymphoma at a different
      site at the time of last follow-up, death, or euthanasia. Median survival time
      for all cats in the study was 190 days (range, 17 to 1,011 days). CONCLUSIONS AND
      CLINICAL RELEVANCE: Results suggested that tarsal lymphoma is an uncommon
      manifestation of lymphoma in cats, and in this study was most commonly
      nonepitheliotropic and of high grade as determined on histologic evaluation.
      Systemic involvement was identified; therefore, thorough staging is recommended
      prior to initiating treatment. Future studies are warranted to evaluate effective
      treatment protocols.

PMID- 24871068
TI  - Racing performance of Thoroughbreds with superficial digital flexor tendonitis
      treated with desmotomy of the accessory ligament of the superficial digital
      flexor tendon: 332 cases (1989-2003).
AB  - OBJECTIVE: To assess postoperative probability of racing, career longevity, and
      convalescent time in Thoroughbred racehorses with moderate to severe superficial
      digital flexor tendonitis (SDFT) in the forelimbs treated by desmotomy of the
      accessory ligament of the superficial digital flexor tendon (ie, superior check
      ligament desmotomy [SCLD]). DESIGN: Retrospective case series. ANIMALS: 332
      Thoroughbred racehorses with SDFT consecutively treated by means of SCLD.
      PROCEDURES: Medical records and racing records were reviewed to assess return to
      racing, number of races completed, time to first race, and lifetime performance.
      The horses were categorized as raced or unraced prior to and after surgery.
      Descriptive statistics including age and treated limb were also recorded.
      RESULTS: Of 332 horses, 228 (69%) returned to racing following injury and
      treatment. Seventy-eight of 118 (66%) horses that had not raced prior to injury
      and 150 of 214 (70%) horses that had raced prior to injury raced after treatment.
      Seventeen of 39 (44%) horses >= 5 years old raced following injury and treatment
      and 211 of 293 (72%) horses <= 4 years old returned to racing. There was no
      difference in the percentages of horses returning to racing for 2-, 3-, or 4-year
      olds. Postoperative infections occurred in 6 of the 332 (2%) horses. Median time
      to first race for horses that raced after surgery was 302 days (range, 48 to
      1,120 days; mean +/- SD, 341 +/- 153 days), with a median of 8 starts/horse after
      surgery (range, 1 to 109 starts; mean +/- SD, 14 +/- 15.8 starts). Of 228 horses
      that returned to racing, 159 (70%) raced >= 5 times after surgery. Sex and
      treated limb did not have a significant effect on return to racing. However,
      horses >= 5 years old were significantly less likely to return to racing,
      compared with younger horses. In horses with unilateral SDFT and < 5 starts, the
      affected and contralateral limbs were both treated, but return to racing was not
      significantly different between horses treated bilaterally versus unilaterally.
      CONCLUSIONS AND CLINICAL RELEVANCE: 228 of 332 (69%) horses with SDFT of the
      forelimb treated with SCLD successfully returned to racing. Convalescent times
      were shorter, compared with previous recommendations, and treated horses had a
      longer racing career after surgery than has been described for other treatment
      modalities. The results of the present study support consideration of SCLD as
      part of a treatment plan for SDFT in Thoroughbred racehorses.

PMID- 24871069
TI  - Associations of health status and conformation with longevity and lifetime
      competition performance in young Swedish Warmblood riding horses: 8,238 cases
      (1983-2005).
AB  - OBJECTIVE: To determine associations of health status and conformation with
      competition longevity and lifetime performance in young Swedish Warmblood riding
      horses. DESIGN: Cohort study and genetic analysis. ANIMALS: 8,238 horses.
      PROCEDURES: Horses were examined for health, conformation, and performance from
      1983 to 2005, when they were 4 to 5 years old, and competition results from 1983
      to 2012 were evaluated. Associations between conformation, health, and talent
      scores of young horses and longevity (years in competition) and lifetime
      performance were analyzed. Odds ratios of competing later in life among horses
      with joint flexion test reactions were determined. Genetic correlations between
      young horse health, conformation, and talent scores and longevity and lifetime
      performance were determined. RESULTS: Good overall 4- to 5-year-old health,
      conformation, and talent scores for performance were phenotypically and
      genetically associated with greater longevity and lifetime performance. Good
      health was genetically correlated (rg = 0.3) to longevity and lifetime
      performance. Among conformation traits, body type and movements in the trot were
      most strongly associated with future longevity; these were genetically correlated
      (rg = 0.2 to 0.3) to longevity and lifetime performance. Intermediate-sized
      horses were associated with highest longevity and lifetime performance. Positive
      flexion test results were associated with lower ORs (OR, 0.59 for moderate to
      severe and 0.76 for minor reactions) of competing later in life, compared with no
      reaction, and were associated with lower longevity (0.4 years). CONCLUSIONS AND
      CLINICAL RELEVANCE: Horses with good health and conformation at a young age had
      better longevity in competitions than the mean. Positive correlations suggested
      that improvement of health and conformation of young horses will enhance their
      future athletic talent and performance.

PMID- 24871071
TI  - Heterogeneous electron transfer at nanoscopic electrodes: importance of
      electronic structures and electric double layers.
AB  - Heterogeneous electron-transfer (ET) processes at solid electrodes play key roles
      in molecular electronics and electrochemical energy conversion and sensing.
      Electrode nanosization and/or nanostructurization are among the major current
      strategies for performance promotion in these fields. Besides, nano
      sized/structured electrodes offer great opportunities to characterize
      electrochemical structures and processes with high spatial and temporal
      resolution. This review presents recent insights into the nanoscopic size and
      structure effects of electrodes and electrode materials on heterogeneous ET
      kinetics, by emphasizing the importance of the electric double-layer (EDL) at the
      electrode/electrolyte interface and the electronic structure of electrode
      materials. It is shown, by general conceptual analysis and recent example
      demonstrations of representative electrode systems including electrodes of
      nanometer sizes and gaps and of nanomaterials such as sp(2) hybridized
      nanocarbons and semiconductor quantum dots, how the heterogeneous ET kinetics,
      the electronic structures of electrodes, the EDL structures at the
      electrode/electrolyte interface and the nanoscopic electrode sizes and structures
      may be related. 

PMID- 24871072
TI  - Is the chronic use of Ferula harmonis to enhance mice erectile function effective
      and safe? A histopathological study.
AB  - Many studies are aimed towards a solution for erectile dysfunction which is a
      worldwide health problem. Medicinal and natural herbal medications have been
      prescribed but their long-term effects are not well known. This study aimed to
      investigate the impact of the chronic administration of F. hermonis root extract
      on the structure of the male mice reproductive organs and their fertility and to
      study the possible protective role of vitamin C. Sixty male albino mice were
      divided into 3 groups: the control, the experimental group that received F.
      hermonis root extract orally (6 mg/kg) for six weeks, and the treated group that
      received F. hermonis plus vitamin C for six weeks. Serum testosterone level and
      mice fertility were assessed. At the end of the experiment mice were sacrificed;
      testis, epididymis, and seminal vesicle were dissected and processed for routine
      histopathological and immunohistochemical examination. The chronic administration
      of F. hermonis extract significantly decreased the level of testosterone and
      partially impaired fertility. Histopathological degenerative changes and a
      significant reduction in estrogen receptor (ER)beta expression were observed in
      testes, epididymis, and seminal vesicle. Vitamin C administration did not
      completely protect the testis from these harmful effects. Although F. hermonis
      roots are recommended to improve erectile and fertility problems, it should be
      used for short periods and with extreme caution. Further clinical studies to
      assess safety and efficacy are needed.

PMID- 24871070
TI  - A new xanthine oxidase inhibitor: the uric acid reduction and additional efficacy
      in CKD patients.

PMID- 24871073
TI  - Mechanical characteristics of harbor seal (Phoca vitulina) vibrissae under
      different circumstances and their implications on its sensing methodology.
AB  - In this paper, the mechanical properties of harbor seal vibrissae immersed in
      various solutions are investigated. As there are no nerves along the length of
      the vibrissae, all the perturbations have to be transmitted to their bases for
      sensing. Hence, quantification and understanding of the mechanical properties of
      the vibrissae are essential in determining the perturbations transmitted to the
      base of the vibrissae. Two experimental setups are devised for measurements of
      the different properties of the vibrissae. The first experimental setup is
      performed with a dynamic mechanical analysis machine. The measured properties in
      these experiments are the modulus of elasticity and the damping of the vibrissae.
      Dry, saline water-immersed, water-immersed and Hanks' balanced salt solution
      (HBSS)-immersed vibrissae are tested to determine the effects of these solutions
      on the properties of the vibrissae. Tests on the duration of immersion are also
      performed with saline water-immersed vibrissae. The second experimental setup is
      performed with a mini-shaker connected to a clamp, which rigidly holds the
      vibrissae at their bases. The measured properties in these experiments are the
      natural frequencies of the vibrissae. The results indicate that the moduli of
      elasticity of the vibrissae are found to decrease along their lengths. However,
      their damping does not vary along the lengths. HBSS-immersed and saline water
      immersed vibrissae show similar characteristics on their properties. An
      analytical model for predicting the natural frequencies of the vibrissae is also
      derived. Strong agreement with previous studies on the underwater sensing
      principle of the harbor seal is also established. 

PMID- 24871075
TI  - Differential estimates of underweight-for-age and growth related morbidity
      according to different growth standards in Indian children.
AB  - OBJECTIVE: To compare the four different growth standards currently used in India
      [WHO (World Health Organization); NCHS (National Center for Health Statistics);
      ICDS (Integrated Child Development Scheme); IAP (Indian Academy of Pediatrics)]
      and determine which better predicts growth related morbidity in children after 3
      mo of follow-up. METHODS: The present cohort study was done at Indira Gandhi
      Government Medical College and Hospital, Nagpur, India. Eligible children were
      those who had; > 3 unformed stools in the prior 24 h, the duration of their
      diarrhea was up to 72 h; and they were able to accept oral fluids or feeds. Main
      outcome measures were classification of the malnutrition status as per each of
      the four growth standards by weight-for-age and weight-for-height z scores at
      three months follow-up. RESULTS: A total of 724 children were included. Mean age
      was 17.8 mo; 40.6 % were <= 12 mo and 59.1 % were males. Estimates of
      malnourished varied by the four standards, (NCHS, 62.2 % to IAP, 7.4 %). When
      separated into 'malnourished' and 'severely malnourished' categories, differences
      were greater, (NCHS, 27.9 % vs. ICDS, 1.9 %). Overall agreement was 'fair'
      (0.2435, z = 22.21, p = 0.0000). After follow-up, children who were 'severely
      malnourished' gained more weight than the 'malnourished'group; however, mean
      weight differed by the four charts [e.g., IAP 767 g (SD +/- 611 g), vs. ICDS
      884.7 g (SD +/- 778 g)]. CONCLUSIONS: Growth standards reported different rates
      of malnourished categories. The utility of the standards to detect children who
      are constitutionally vs. pathologically small is questionable. Monitoring the
      nutritional status of children at both the individual level and at population
      level has implications for clinical practice, policy development and resource
      allocation.

PMID- 24871074
TI  - Comparative analysis of the substrate specificity of trans- versus cis
      acyltransferases of assembly line polyketide synthases.
AB  - Due to their pivotal role in extender unit selection during polyketide
      biosynthesis, acyltransferase (AT) domains are important engineering targets. A
      subset of assembly line polyketide synthases (PKSs) are serviced by discrete,
      trans-acting ATs. Theoretically, these trans-ATs can complement an inactivated
      cis-AT, promoting introduction of a noncognate extender unit. This approach
      requires a better understanding of the substrate specificity and catalytic
      mechanism of naturally occurring trans-ATs. We kinetically analyzed trans-ATs
      from the disorazole and kirromycin synthases and compared them to a
      representative cis-AT from the 6-deoxyerythronolide B synthase (DEBS). During
      transacylation, the disorazole AT favored malonyl-CoA over methylmalonyl-CoA by
      >40000-fold, whereas the kirromycin AT favored ethylmalonyl-CoA over
      methylmalonyl-CoA by 20-fold. Conversely, the disorazole AT had broader
      specificity than its kirromycin counterpart for acyl carrier protein (ACP)
      substrates. The presence of the ACP had little effect on the specificity
      (k(cat)/K(M)) of the cis-AT domain for carboxyacyl-CoA substrates but had a
      marked influence on the corresponding specificity parameters for the trans-ATs,
      suggesting that these enzymes do not act strictly by a canonical ping-pong
      mechanism. To investigate the relevance of the kinetic analysis of isolated ATs
      in the context of intact PKSs, we complemented an in vitro AT-null DEBS assembly
      line with either trans-AT. Whereas the disorazole AT efficiently complemented the
      mutant PKS at substoichiometric protein ratios, the kirromycin AT was
      considerably less effective. Our findings suggest that knowledge of both
      carboxyacyl-CoA and ACP specificity is critical to the choice of a trans-AT in
      combination with a mutant PKS to generate novel polyketides.

PMID- 24871076
TI  - Burkholderia cepacia sepsis among neonates.
AB  - Burkholderia cepacia is a rare cause of sepsis in newborns and its transmission
      involves human contact with heavily contaminated medical devices and
      disinfectants. The authors aimed to determine epidemiology, clinical features,
      antibiotic sensitivity pattern, complications and outcome of blood culture proven
      B. cepacia infections in 12 neonates. All neonates were outborn, 5 preterm and 7
      term. B. cepacia was isolated from blood in all and concurrently from CSF in
      three neonates. Lethargy and respiratory distress (41.7 %) were major presenting
      features. Five newborns (41.7 %) required mechanical ventilation for 3-7 d.
      Highest bacterial susceptibility was observed for meropenem (100 %), followed by
      cefoperazone-sulbactam, piperacillin-tazobactam, sulfamethoxazole-trimethoprim
      (all 83 %), ceftazidime (75 %) and ciprofloxacin (42 %). Piperacillin-tazobactam,
      ciprofloxacin and cotrimoxazole either singly or in combination led to complete
      recovery of 11 (91.7 %) newborns; one developed hydrocephalus. Eight of nine
      infants who completed 6 mo follow up were normal. Prompt recognition and
      appropriate antibiotic therapy for B. cepacia infection results in complete
      recovery in majority.

PMID- 24871077
TI  - Rational management of epilepsy.
AB  - Management of epilepsies in children has improved considerably over the last
      decade, all over the world due to the advances seen in the understanding of the
      patho-physiology of epileptogenesis, availability of both structural and
      functional imaging studies along with better quality EEG/video-EEG recordings and
      the availability of a plethora of newer anti-epileptic drugs which are tailormade
      to act on specific pathways. In spite of this, there is still a long way to go
      before one is able to be absolutely rational about which drug to use for which
      type of epilepsy. There have been a lot of advances in the area of epilepsy
      surgery and is certainly gaining ground for specific cases. Better understanding
      of the genetic basis of epilepsies will hopefully lead to a more rational
      treatment plan in the future. Also, a lot of work needs to be done to dispel
      various misunderstandings and myths about epilepsy which still exists in our
      country. 

PMID- 24871078
TI  - Treatment of chronic phase chronic myeloid leukemia with imatinib.
AB  - OBJECTIVE: To report outcomes of Chronic Myeloid Leukemia (CML) treated with
      upfront imatinib. METHODS: Outcomes of children (<=18 y) with chronic phase CML
      (CML-CP) treated with imatinib over a 5 y (2003-2008) period were retrospectively
      analyzed to quantify responses, progression free survival (PFS) and overall
      survival (OS). RESULTS: Thirty-one patients (age range: 6-18 y) received therapy
      with imatinib 260-300 mg/m(2). Thirty (97 %) achieved complete hematological
      response at a median of 2 mo from start of treatment. Major and complete
      cytogenetic response rates at 2 y were 82 % and 70 % respectively. After a median
      follow up of 49.2 mo the 5 year PFS and OS were 68 % and 76 % respectively. Out
      of the 16 patients with documented Complete Cytogenetic Response (CCR) at 2 y,
      none progressed during subsequent follow up. There were no serious toxicities.
      Most patients who progressed, died of the disease. CONCLUSIONS: Imatinib is a
      reasonable first line therapy in pediatric CML-CP, which is effective and well
      tolerated. Outcomes are comparable to those reported from the West. Availability
      of second line agents and increased access to stem cell transplantation could
      further improve outcomes.

PMID- 24871079
TI  - Maternal perceptions of supervision in pre-school-aged children: a qualitative
      approach to understanding differences between families living in affluent and
      disadvantaged areas.
AB  - AIM: To explore maternal perceptions of supervision and childhood unintentional
      injury in order to develop understanding and explanation for differences in
      unintentional injury rates between an advantaged and disadvantaged area.
      BACKGROUND: Unintentional injury is the second cause of mortality and a
      significant cause of morbidity in the zero to four year age group. Children
      living in socio-economic disadvantage are at a greater risk of unintentional
      injury than their more affluent counter-parts. METHODS: Qualitative study using
      semi-structured interviews; content data analysis was undertaken. Participants
      included 37 mothers with a child aged less than five years; 16 living in an area
      of disadvantage (and high rate of childhood unintentional injury) and 21 living
      in an advantaged area (and low rate of childhood unintentional injury). FINDINGS:
      Parents in both areas described the importance of parental supervision in
      reducing child unintentional injury risks. Parents in both areas used listening
      as a supervision strategy. Parents in both areas described how 'when the child
      goes quiet' that is a cue for them to make a visual check on the child. Listening
      was used more for boys than girls in both areas, but parents in the advantaged
      area used listening as a supervision strategy more frequently than those in the
      disadvantaged area. Parents described supervision strategies as being shaped by
      child character and age rather than child gender. Parents in both areas described
      similar strategies for managing distractions. An important difference was found
      with regard to older siblings; parents living in the advantaged area described
      older siblings as an injury risk to younger children. Parents in the
      disadvantaged area described older siblings as providing some supervision for
      younger children. Parents living in disadvantaged circumstances may face greater
      challenges with regard to supervision than parents living in advantaged
      circumstances and this may partly explain differences in injury risk.

PMID- 24871080
TI  - Outcomes for patients with obstructing colorectal cancers treated with one-stage
      surgery using transanal drainage tubes.
AB  - BACKGROUND: Acute colorectal obstruction requires immediate surgical treatment.
      Although one-stage surgery with transanal drainage tubes (TDT) is reportedly safe
      and feasible, the long-term outcome of this procedure remains unclear. AIM: To
      assess the outcome of one-stage surgery using TDT in the acute left colon or
      rectal obstructions due to colorectal carcinomas. METHODS: Clinicopathological
      data were recorded from patients with colorectal cancer with acute obstructions
      between 2006 and 2013. RESULTS: A total of 43 patients were enrolled including 29
      males and 14 females. Among 39 patients, TDT was successful in 33 (84 %) and was
      incomplete in 6. Thus, 33 patients received one-stage surgery with TDT
      decompression, and 9 patients, including 6 with incomplete decompression,
      received one-stage surgery with no decompression. No significant differences in
      clinicopathological factors were observed between decompression and non
      decompression groups. Adjusted analyses revealed that decompression using TDT was
      significantly associated with OS (hazard ratio 0.24; 95 % confidence interval,
      0.08-0.72; p = 0.01). Furthermore, OS in the TDT decompression group was
      significantly longer than that in the non-decompression group (p = 0.01).
      CONCLUSIONS: One-stage surgery with decompression using TDT may be effective to
      avoid stomas and to improve overall survival in patients with obstructing
      colorectal cancers.

PMID- 24871081
TI  - Management of non-parasitic splenic cysts: does size really matter?
AB  - BACKGROUND: Splenic cysts are relatively rare clinical entities and are often
      diagnosed incidentally upon imaging conducted for a variety of clinical
      complaints. They can be categorized as primary or secondary based on the presence
      or absence of an epithelial lining. Primary cysts are further subdivided into
      those that are and are not secondary to parasitic infection. The treatment of non
      parasitic splenic cysts (NPSC) has historically been dictated by two primary
      factors: the presence of symptoms attributable to the cyst and cyst size greater
      or less than 5 cm. While it is appropriate to resect a symptomatic lesion, the
      premise of recommending operative intervention based on size is not firmly
      supported by the literature. METHODS: In the current study, we identified 115
      patients with splenic cysts and retrospectively reviewed their management that
      included aspiration, resection, or observation. RESULTS: Our data reveal a
      negative overall growth rate of asymptomatic cysts, a high recurrence rate after
      percutaneous drainage, as well as demonstrate the safety of observing
      asymptomatic lesions over time. CONCLUSION: We conclude that observation of
      asymptomatic splenic cysts is safe regardless of size and that aspiration should
      be reserved for those who are not surgical candidates or in cases of diagnostic
      uncertainty.

PMID- 24871082
TI  - Surgical resection is better than transarterial chemoembolization for
      hepatocellular carcinoma beyond Milan criteria independent of performance status.
AB  - BACKGROUND AND AIMS: Performance status is tightly linked with survival in
      patients with hepatocellular carcinoma (HCC). We investigated the impact of
      performance status on HCC patients beyond the Milan criteria receiving surgical
      resection (SR) or transarterial chemoembolization (TACE). METHODS: A total of 909
      patients with HCC beyond the Milan criteria were retrospectively analyzed by
      using propensity score analysis. RESULTS: The baseline characteristics were
      similar between the SR and TACE group for patients with performance status 0 in
      the propensity model. More patients in the TACE group with performance status >=1
      had Child-Turcotte-Pugh class A compared to the SR group (p = 0.044) in the
      propensity model. SR provided significantly better long-term overall survival
      than TACE in patients selected in the propensity model regardless of performance
      status (both p < 0.05). In the Cox proportional hazards model, TACE was
      associated with 2.279-fold and 3.066-fold increased risk of mortality in
      performance status 0 and performance status >=1 in the propensity model (95%
      confidence interval, 1.476-3.591 and 1.570-5.989), respectively. CONCLUSIONS: For
      either performance status 0 or >=1 HCC patients beyond the Milan criteria, SR
      provides significantly better long-term survival than TACE. SR should be
      considered a priority treatment in these patients independent of performance
      status.

PMID- 24871083
TI  - Abdominopelvic splenosis--an unusual cause of tenesmus.
AB  - Splenosis is a rare condition defined as seeding and autotransplantation of
      splenic tissue, typically after blunt abdominal trauma (e.g. from road traffic
      collision). Sites of splenosis ranging from intrathoracic to intrapelvic have
      been reported, and symptoms vary greatly depending on the site and size of
      lesions. We present the use of Tc-99m sulphur colloid SPECT/CT in diagnosing a
      case of multiple abdominopelvic splenosis as the cause of new-onset tenesmus and
      constipation, which was initially thought to be due to colorectal malignancy, 47
      years following the initial abdominal trauma.

PMID- 24871085
TI  - Regional variations in correlation between photopic negative response of focal
      electoretinograms and ganglion cell complex in glaucoma.
AB  - PURPOSE: To determine regional variations in a structure-function relationship,
      we correlated the the photopic negative response (PhNR) of the focal
      electoretinogram (ERG) with the ganglion cell complex (GCC) thickness in
      different retinal regions in patients with open angle glaucoma (OAG). METHODS:
      Fifty-one eyes of 51 OAG patients (OAG group) and 17 eyes of 17 normal volunteers
      (control group) were studied. The OAG patients had different degrees of glaucoma
      ranging from early to advanced stages. The focal ERGs were elicited by a white,
      15 degrees  hemispherical stimulus placed superior or inferior to the fovea.
      Focal ERGs were also elicited by a half annulus placed superior or inferior to
      the macular region. The diameter of the inner border of the annulus was 15
      degrees  and that of the outer border was 30 degrees . The average GCC thickness
      in areas corresponding to the location of the stimuli was measured in SD-OCT
      images. RESULTS: The PhNR amplitude and PhNR/b-wave amplitude ratio were
      significantly correlated with the GCC thickness in the superior and inferior
      hemispherical areas (p < 0.0001). These ERG parameters were weakly correlated
      with the GCC thickness in the superior and inferior semi-annular areas (p <
      0.05). There were significant differences in the slopes of the regression lines
      plotting the GCC thickness and the PhNR amplitude or the PhNR/b-wave amplitude
      ratio between the spherical and semi-annular areas (superior: p < 0.01, inferior:
      p < 0.0005). CONCLUSIONS: The thinning of the GCC affects the RGC function
      measured by the PhNR more strongly in the central retinal area than in the
      surrounding retinal areas.

PMID- 24871086
TI  - "Nano-oddities": unusual nucleic acid assemblies for DNA-based nanostructures and
      nanodevices.
AB  - CONSPECTUS: DNA is an attractive polymer building material for nanodevices and
      nanostructures due to its ability for self-recognition and self-assembly.
      Assembly relies on the formation of base-specific interactions that allow strands
      to adopt structures in a controllable fashion. Most DNA-based higher order
      structures such as DNA cages, 2D and 3D DNA crystals, or origamis are based on
      DNA double helices stabilized by Watson-Crick complementarity. A number of
      nonclassical pairing patterns are possible between or among DNA strands; these
      interactions result in formation of unusual structures that include, but are not
      limited to, G-quadruplexes, i-motifs, triplexes, and parallel-stranded duplexes.
      These structures create greater diversity of DNA-based building blocks for
      nanomaterials and have certain advantages over conventional duplex DNA, such as
      enhanced thermal stability and sensitivity to chemical stimuli. In this Account,
      we briefly introduce these alternative DNA structures and describe in detail
      their utilization in a variety of nanomaterials and nanomachines. The field of
      DNA "nano-oddities" emerged in the late 1990s when for the first time a DNA
      nanomachine was designed based on equilibrium between B-DNA and noncanonical,
      left-handed Z-DNA. Soon after, "proof-of-principle" DNA nanomachines based on
      several DNA "oddities" were reported. These machines were set in motion by the
      addition of complementary strands (a principle used by many B-DNA-based
      nanodevices), by the addition of selected cations, small molecules, or proteins,
      or by a change in pH or temperature. Today, we have fair understanding of the
      mechanism of action of these devices, excellent control over their performance,
      and knowledge of basic principles of their design. pH sensors and pH-controlled
      devices occupy a central niche in the field. They are usually based on i-motifs
      or triplex DNA, are amazingly simple, robust, and reversible, and create no waste
      apart from salt and water. G-quadruplex based nanostructures have unusually high
      stability, resist DNase and temperature, and display high selectivity toward
      certain cations. The true power of using these "nano-oddities" comes from
      combining them with existing nanomaterials (e.g., DNA origami, gold
      nanoparticles, graphene oxide, or mesoporous silica) and integrating them into
      existing mechanical and optoelectronic devices. Creating well-structured
      junctions for these interfaces, finding appropriate applications for the vast
      numbers of reported "nano-oddities", and proving their biological innocence
      comprise major challenges in the field. Our Account is not meant to be an all
      inclusive review of the field but should give a reader a firm grasp of the
      current state of DNA nanotechnology based on noncanonical DNA structures.

PMID- 24871087
TI  - HIV enteropathy and aging: gastrointestinal immunity, mucosal epithelial barrier,
      and microbial translocation.
AB  - PURPOSE OF REVIEW: Despite decreases in morbidity and mortality as a result of
      antiretroviral therapy, gastrointestinal dysfunction remains common in HIV
      infection. Treated patients are at risk for complications of 'premature' aging,
      such as cardiovascular disease, osteopenia, neurocognitive decline, malignancies,
      and frailty. This review summarizes recent observations in this field. RECENT
      FINDINGS: Mucosal CD4 lymphocytes, especially Th17 cells, are depleted in acute
      HIV and simian immune deficiency virus (SIV) infections, although other cell
      types also are affected. Reconstitution during therapy often is incomplete,
      especially in mucosa. Mucosal barrier function is affected by both HIV infection
      and aging and includes paracellular transport via tight junctions and uptake
      through areas of apoptosis; other factors may affect systemic antigen exposure.
      The resultant microbial translocation is associated with systemic immune
      activation in HIV and SIV infections. There is evidence of immune activation and
      microbial translocation in the elderly. The immune phenotypes of immunosenescence
      in HIV infection and aging appear similar. There are several targets for
      intervention; blockage of residual mucosal virus replication, preventing antigen
      uptake, modulating the microbiome, improving T cell recovery, combining therapies
      aimed at mucosal integrity, augmenting mucosal immunity, and managing traditional
      risk factors for premature aging in the general population. SUMMARY: Aging may
      interact with HIV enteropathy to enhance microbial translocation and immune
      activation.

PMID- 24871084
TI  - Lung macrophages "digest" carbon nanotubes using a superoxide/peroxynitrite
      oxidative pathway.
AB  - In contrast to short-lived neutrophils, macrophages display persistent presence
      in the lung of animals after pulmonary exposure to carbon nanotubes. While
      effective in the clearance of bacterial pathogens and injured host cells, the
      ability of macrophages to "digest" carbonaceous nanoparticles has not been
      documented. Here, we used chemical, biochemical, and cell and animal models and
      demonstrated oxidative biodegradation of oxidatively functionalized single-walled
      carbon nanotubes via superoxide/NO* -> peroxynitrite-driven oxidative pathways of
      activated macrophages facilitating clearance of nanoparticles from the lung. 

PMID- 24871088
TI  - The effects of HIV and aging on brain functions: proposing a research framework
      and update on last 3 years' findings.
AB  - PURPOSE OF REVIEW: The effect of HIV and aging on brain functions is an
      increasingly important topic of research: HIV-infected (HIV+) persons aged >=50
      represent a growing part of the HIV epidemic. Research is embracing this new
      axis, but there has been a lack of conceptualization of the factors that are at
      stake in both aging and HIV. To start to remedy this theoretical limitation, we
      are proposing a research framework in the hope that it will optimize how research
      questions and findings are formulated. Moreover, in the light of this proposed
      research framework, we review the last 3  years' research findings. RECENT
      FINDINGS: Our review highlights that as HIV+ persons are aging, there is some
      signal for acceleration of normal aging processes and facilitated expression of
      age-associated diseases. Evidence for dramatic neurodegeneration in aging HIV+
      persons remains limited and may be different in nature to typical
      neurodegenerative processes. Also, it should be kept in mind that most HIV+
      persons are still below age 60. The vast majority of studies are still cross
      sectional thereby underlining the critical importance of longitudinal studies to
      fully assess the effect of comorbidities. SUMMARY: The complex effects of aging
      and nonaging comorbidities and key HIV effects (as opposed to only HIV status)
      need to be taken into account in future research by increasing sample size and
      selecting the most appropriate control group(s). Ideally, life-span studies
      should be established using neuropsychological and neuroimaging outcomes that
      have a proven track record in both HIV-related brain injury and brain aging.
      These would be similar to those that exist in non-HIV aging research and would
      optimally account for comorbidity effects and survivor bias.

PMID- 24871090
TI  - Aging with HIV: osteoporosis and fractures.
AB  - PURPOSE OF REVIEW: Osteoporosis remains an important focus of contemporary
      research in HIV, with co-morbidities and mortality from non-AIDS illnesses now a
      major barrier to normal lifespan in many populations living with HIV. This review
      outlines the major recent advances in our understanding of osteoporosis and
      fractures in those living with HIV and identifies remaining gaps in our knowledge
      of this complex but increasingly important aspect of aging research in HIV.
      RECENT FINDINGS: Low bone mineral density (BMD), osteoporosis and fractures are
      all more common in those living with HIV, with recent data pointing for the first
      time to causal links between low BMD and fractures in those with HIV. The natural
      history and pathogenesis of osteoporosis in HIV and the epidemiology of fractures
      in this vulnerable population differ considerably from the general population,
      with both disease-related and treatment-related factors both contributing to its
      development through alterations in bone turnover and defects in bone
      architecture. SUMMARY: Only through a greater understanding of the pathogenesis
      can appropriate screening and preventive measures be taken in people living with
      HIV to preserve bone health as they age.

PMID- 24871089
TI  - Patient-centered care for people living with multimorbidity.
AB  - PURPOSE OF REVIEW: The purpose of this review is to consider a patient-centred
      approach to the care of people living with HIV (PLWH) who have multimorbidity,
      irrespective of the specific conditions. RECENT FINDINGS: Interdisciplinary care
      to achieve patient-centred care for people with multimorbidity is recognized as
      important, but the evaluation of models designed to achieve this goal are needed.
      Key elements of such approaches include patient preferences, interpretation of
      the evidence, prognosis as a tool to inform patient-centred care, clinical
      feasibility and optimization of treatment regimens. SUMMARY: Developing and
      evaluating the best models of patient-centred care for PLWH who also have
      multimorbidity is essential. This challenge represents an opportunity to leverage
      the lessons learned from the care of people with multimorbidity in general, and
      vice versa.

PMID- 24871091
TI  - Aging and HIV: an evolving understanding.

PMID- 24871092
TI  - Isolation, expansion and transplantation of postnatal murine progenitor cells of
      the enteric nervous system.
AB  - Neural stem or progenitor cells have been proposed to restore gastrointestinal
      function in patients suffering from congenital or acquired defects of the enteric
      nervous system. Various, mainly embryonic cell sources have been identified for
      this purpose. However, immunological and ethical issues make a postnatal cell
      based therapy desirable. We therefore evaluated and quantified the potential of
      progenitor cells of the postnatal murine enteric nervous system to give rise to
      neurons and glial cells in vitro. Electrophysiological analysis and BrdU uptake
      studies provided direct evidence that generated neurons derive from expanded
      cells in vitro. Transplantation of isolated and expanded postnatal progenitor
      cells into the distal colon of adult mice demonstrated cell survival for 12 weeks
      (end of study). Implanted cells migrated within the gut wall and differentiated
      into neurons and glial cells, both of which were shown to derive from
      proliferated cells by BrdU uptake. This study indicates that progenitor cells
      isolated from the postnatal enteric nervous system might have the potential to
      serve as a source for a cell based therapy for neurogastrointestinal motility
      disorders. However, further studies are necessary to provide evidence that the
      generated cells are capable to positively influence the motility of the diseased
      gastrointestinal tract. 

PMID- 24871093
TI  - Contrasting effects of geographical separation on the genetic population
      structure of sympatric species of mites in avocado orchards.
AB  - Oligonychus punicae and Oligonychus perseae (Acari: Tetranychidae) are the most
      important mite species affecting avocado orchards in Mexico. Here we used
      nucleotide sequence data from segments of the nuclear ribosomal internal
      transcribed spacers (ITS1 and ITS2) and mitochondrial cytochrome oxidase subunit
      I (COI) genes to assess the phylogenetic relationships between both sympatric
      mite species and, using only ITS sequence data, examine genetic variation and
      population structure in both species, to test the hypothesis that, although both
      species co-occur, their genetic population structures are different in both
      Michoacan state (main producer) and Mexico state. Phylogenetic analysis showed a
      clear separation between both species using ITS and COI sequence information.
      Haplotype network analysis done on 24 samples of O. punicae revealed low genetic
      diversity with only three haplotypes found but a significant geographical
      population structure confirmed by analysis of molecular variance (AMOVA) and
      Kimura-2-parameter (K2P) analyses. In addition, a Mantel test revealed that
      geographical isolation was a factor responsible for the genetic differentiation.
      In contrast, analyses of 22 samples of O. perseae revealed high genetic diversity
      with 15 haplotypes found but no geographical structure confirmed by the AMOVA,
      K2P and Mantel test analyses. We have suggested that geographical separation is
      one of the most important factors driving genetic variation, but that it affected
      each species differently. The role of the ecology of these species on our
      results, and the importance of our findings in the development of monitoring and
      control strategies are discussed.

PMID- 24871105
TI  - [Adolescent nutrition: the urgent need for acting immediately].

PMID- 24871104
TI  - Metamicrobiomics in herbivore beetles of the genus Cryptocephalus
      (Chrysomelidae): toward the understanding of ecological determinants in insect
      symbiosis.
AB  - The Cryptocephalus marginellus (Coleoptera: Chrysomelidae) complex is composed by
      six species that are supposed to have originated by events of allo- or parapatric
      speciation. In the present study we investigated the alternative hypotheses that
      the bacterial communities associated with six populations of this species complex
      are shaped by environmental factors, or reflect the proposed pattern of
      speciation. The microbiota associated with the six populations, from five species
      of the complex, have been characterized through 16S rRNA pyrotag sequencing.
      Based on a 97% sequence similarity threshold, data were clustered into 381 OTUs,
      which were analyzed using a variety of diversity indices. The microbiota of C.
      acquitanus and C. marginellus (Calanques) were the most diverse (over 100 OTUs),
      while that from C. zoiai yielded less bacterial diversity (45 OTUs). Taxonomic
      assignment revealed Proteobacteria, Tenericutes and Firmicutes as the dominant
      components of these beetles' microbiota. The most abundant genera were Ralstonia,
      Sphingomonas, Rickettsia, and Pseudomonas. Different strains of Rickettsia were
      detected in C. eridani and C. renatae. The analysis of beta-diversity revealed
      high OTU turnover among the populations of C. marginellus complex, with only few
      shared species. Hierarchical clustering taking into account relative abundances
      of OTUs does not match the phylogeny of the beetles, therefore we hypothesize
      that factors other than phylogenetic constraints play a role in shaping the
      insects' microbiota. Environmental factors that could potentially affect the
      composition of bacterial communities were tested by fitting them on the results
      of a multi-dimensional scaling analysis. No significant correlations were
      observed towards the geographic distances or the host plants, while the
      composition of the microbiota appeared associated with altitude. The metabolic
      profiles of the microbiotas associated with each population were inferred from
      bacterial taxonomy, and interestingly, the obtained clustering pattern was
      consistent with the host phylogeny. 

PMID- 24871103
TI  - Osteopontin deletion prevents the development of obesity and hepatic steatosis
      via impaired adipose tissue matrix remodeling and reduced inflammation and
      fibrosis in adipose tissue and liver in mice.
AB  - Osteopontin (OPN) is a multifunctional extracellular matrix (ECM) protein
      involved in multiple physiological processes. OPN expression is dramatically
      increased in visceral adipose tissue in obesity and the lack of OPN protects
      against the development of insulin resistance and inflammation in mice. We sought
      to unravel the potential mechanisms involved in the beneficial effects of the
      absence of OPN. We analyzed the effect of the lack of OPN in the development of
      obesity and hepatic steatosis induced by a high-fat diet (HFD) using OPN-KO mice.
      OPN expression was upregulated in epididymal white adipose tissue (EWAT) and
      liver in wild type (WT) mice with HFD. OPN-KO mice had higher insulin
      sensitivity, lower body weight and fat mass with reduced adipose tissue ECM
      remodeling and reduced adipocyte size than WT mice under a HFD. Reduced MMP2 and
      MMP9 activity was involved in the decreased ECM remodeling. Crown-like structure
      number in EWAT as well as F4/80-positive cells and Emr1 expression in EWAT and
      liver increased with HFD, while OPN-deficiency blunted the increase. Moreover,
      our data show for the first time that OPN-KO under a HFD mice display reduced
      fibrosis in adipose tissue and liver, as well as reduced oxidative stress in
      adipose tissue. Gene expression of collagens Col1a1, Col6a1 and Col6a3 in EWAT
      and liver, as well as the profibrotic cytokine Tgfb1 in EWAT were increased with
      HFD, while OPN-deficiency prevented this increase. OPN deficiency prevented
      hepatic steatosis via reduction in the expression of molecules involved in the
      onset of fat accumulation such as Pparg, Srebf1, Fasn, Mogat1, Dgat2 and Cidec.
      Furthermore, OPN-KO mice exhibited higher body temperature and improved BAT
      function. The present data reveal novel mechanisms of OPN in the development of
      obesity, pointing out the inhibition of OPN as a promising target for the
      treatment of obesity and fatty liver. 

PMID- 24871106
TI  - [Need for research collaboration between cardiologists and emergency service
      doctors].
AB  - Time is a key factor when tackling acute coronary diseases and syndromes. The
      current organization of health services means that the first minutes of care are
      not carried out in cardiology rooms and do not depend on cardiologists. Instead
      they take place in the pre-hospital setting of emergency medical services (EMS)
      and in hospital accident and emergency services (A&E) and in the first phase this
      attention is provided by emergency doctors. Therefore, to obtain the best
      possible result for the patient it is necessary that there should be extensive
      two-way collaboration between cardiologists and emergency service doctors. This
      article analyzes these needs and tries to identify areas of improvement in two of
      the most frequent acute coronary processes: acute coronary syndrome and acute
      cardiac insufficiency. 

PMID- 24871107
TI  - [Validity of clinical register of pressure ulcers].
AB  - BACKGROUND: To compare pressure ulcers (PU) found in this prospective
      observational study with PU recorded in the Electronic Medical Record (EHR).
      METHOD: We use a prospective observational study to record PU, with daily
      monitoring by an observer in the medical-surgical units of hospitalization, as
      well as a clinical record review of PU tracking. Patient monitoring was conducted
      between December 2008 and March 2009 at Fuenlabrada University hospital. We
      calculated the absolute and relative frequency of PU in the patients followed, as
      well as the association among qualitative variables and the validity of the
      registration in the EHR with regard to the reference standard, the observational
      study. RESULTS: Among the 1,001 patients followed-up in this study, 42 of them
      showed PU (4.2% of the total patients), compared to 25 (2.5%) patients who had
      registered PU in the Electronic Health Record, which means a statistically
      significant difference (p<0.001). The record of PU presents a Kappa index of
      0.548, with a sensitivity of 47.62 % and a specificity of 99.48 %, with regard to
      the reference standard, the observational study. CONCLUSION: The number of
      patients with pressure ulcers almost doubled if the observational data collection
      is done by an expert nurse compared to what was recorded in the EHR.

PMID- 24871108
TI  - [Variability in the implementation of health-promoting community activities in
      Spain].
AB  - BACKGROUND: To describe the variability in the application of community
      activities (CA) promoting health, in support received, in training, and in
      evaluation of the participation of professionals, administration and social
      partners in these. METHODS: Survey to key informants identified in each region
      with the help of the Spanish Society of Family and Community Medicine. The
      questionnaire included a definition of a health promotion community activity. The
      study was conducted in 2008. RESULTS: There was variability in community
      activities by region. The most involved professionals are nurses and social
      workers. Most of the regions (15 of 17) offer training in these issues to their
      professionals, especially in health education. It is less frequent to offer
      training to family medicine residents (10 of 17 regions) and to the different
      nursing specialties (6 of 17). The main institutional support comes from primary
      health care management, regional health services, municipalities, and public
      health services, and non-institutional support from scientific societies, civic
      associations and NGOs. On the evaluation of the involvement of different
      organizations and institutions in these activities, the only entities receiving
      pass grades were NGOs (3 out of 5) and primary health care (2.5 out of 5).
      CONCLUSIONS: There is a high variability in the ways of supporting and promoting
      community activities in each region and consequently in their dissemination and
      implementation by primary health care teams. Nurses and social workers are key
      players in this process.

PMID- 24871109
TI  - [Association of age and sex with intensity of exposure to bicycle use in Spain,
      1993-2009].
AB  - BACKGROUND: To estimate the association of age and sex with the intensity of
      exposure of cyclists in Spain, between 1993 and 2009, in a global way and for
      subtypes of use. METHODS: From the distribution of cyclists passively involved in
      collisions with other vehicles included in the register of the Spanish General
      Traffic Directorate between 1993 and 2009, we have estimated the increase in
      intensity of exposure by age groups and sex, for global exposure and for subtypes
      of exposure (e.g. riding with or without a helmet, or riding on an open road or
      in urban areas), using males aged 45-49 as a reference. RESULTS: Males have a
      greater exposure than females and this difference increases with age, although it
      has tended to decrease in recent years. In both sexes the exposure is greater in
      young people and goes down with age, while in males the excess in young people
      has disappeared in recent years. Regarding subtypes of use, female underexposure
      riding on an open road should be highlighted, as well as overexposure in both
      women and extreme age groups among non-helmet users. CONCLUSION: There is a close
      association of age and sex with the intensity of bicycle use, which changes
      depending on the type of use and the time period considered. Consequently,
      estimations of the effect of factors affecting the accident rate and the
      morbidity and mortality of cyclists in Spain have to be adjusted by the age and
      sex of the cyclist.

PMID- 24871110
TI  - [Food consumption patterns among adolescents].
AB  - BACKGROUND: Adolescence is a critical time for the establishment of healthy
      eating habits. The objective was to analyze food consumption patterns among
      adolescents and their relationship with family and social factors. METHODS:
      Multicentre observational cross-sectional descriptive study using a food
      frequency questionnaire for the last week. It was answered anonymously. The
      adolescent's age/gender, parents' studies/occupation and school's location/type
      were included. The population sample was composed of 1,095 adolescents in sixth
      grade at primary schools from an Andalusian region. They were chosen by
      polietapic random sampling that distinguished between public/private and
      capital/provincial schools. RESULTS: 1,005 surveys were analyzed. The mean age is
      11.45 (SD: 0.59). Fifty-three percent were male. The intake of dairy products
      (only two-thirds taken daily), pasta, fruit and vegetables (daily consumption of
      30%) is deficient. Sixty-four point five percent consume legumes weekly. Fish
      consumption is equal to meat, with a preference for poultry. More than half
      consume red meat daily. Olive oil is preferred. The intake of "empty calories"
      (fast food, candies, soft drink) is high. Through multivariate analysis the
      existence of clusters of healthy and unhealthy foods, related to the social
      status of the parents and the type of school, is proved. CONCLUSIONS: A healthy
      diet based on the nutritional pyramid is not the consumption pattern in the
      adolescents surveyed. There is a low consumption of diary products, legumes,
      fruits and vegetables. There is a relationship between the social class of the
      family and consumption patterns (healthy and unhealthy). Health strategies are
      needed to modify such inappropriate consumption.

PMID- 24871111
TI  - [Suspected diagnosis of cancer in hospital emergency services].
AB  - BACKGROUND: To measure the frequency, trends and distribution of cancers with
      suspected diagnosis in the Hospital Emergency Services (HES) in Asturias during
      2006-12. To describe the clinical characteristics of these cancers and to
      determine if they differ from those whose diagnosis is made in other services.
      METHODS: Population based descriptive study of cancers registered in the Hospital
      Tumour Registry of Asturias (Spain), which provided data of patient
      characteristics, cancer variables (site, histology, stage, metastasis and delay),
      the hospital and service of diagnosis. Patients with confirmed diagnosis of
      cancer (non-melanoma of skin excluded) in the study period were included
      (N=26,020). Differences of cancer cases according to the service that had
      performed the suspected diagnosis were analyzed. We performed regression analysis
      of the time between the first symptom and the suspected diagnosis, the definitive
      diagnosis and treatment, controlling main confounders. RESULTS: Seven point nine
      percent (n=2,056) of all cancer cases were suspected in a HES (annual minimum of
      5.3% and maximum 10.4%, with an upward trend). These patients were mainly men
      (60.6%), with a mean age of 67.7 years, and with lung (21.0%) and colon cancer
      (15.5%). The HES ranks 6th place in the list of services which diagnosed cancer.
      There was more diagnosis of advanced tumours (33.0%) and metastasis (29.5%) in
      the HES. The HES halved the time between the first symptom and the SD (-63.3
      days; p<0.001), and between definitive diagnosis and initiation of treatment (
      15.9 days; p<0.001) compared to the other services. CONCLUSIONS: The HES
      contribute significantly to suspected cancer diagnosis, mainly advanced and
      metastatic tumours in the respiratory and digestive system, whose symptoms escape
      accidental diagnosis conducted in primary care, and they start abruptly.

PMID- 24871112
TI  - [Key elements for patients and caregivers in the process of living with
      Parkinson's disease].
AB  - BACKGROUND: Parkinson's disease has a considerable impact on people's lives. It
      is necessary to identify the key elements that influence the process of living
      with Parkinson's disease so that health professionals can help patients and their
      relatives to live as well as possible with the changes and limitations produced
      by the disease. MATERIAL AND METHODS: A qualitative descriptive study was
      realized. This study corresponded to the first phase of a sequential, exploratory
      design (mixed method) that in turn included a quantitative phase. A multicentre
      project was carried out. Convenience sampling was applied to collect data, a semi
      structured interview was realized individually with patients and carer-relatives
      and two questionnaires with patients: the Hoehn & Yahr scale and the PDNMS
      questionnaire. Content analysis of the interviews and a statistical description
      of the questionnaires were used. RESULTS: The sample was made up of 46
      participants. Three key elements were identified in the process of living with
      Parkinson's disease: acceptance, adaptation and self-management. These elements
      conditioned the modes of living with Parkinson's disease: positive living,
      characterized by feelings of harmony, balance and naturalness; negative living
      characterized be feelings of frustration, loss of control and self-esteem.
      CONCLUSIONS: It is essential for health professionals to have a deep
      understanding of these elements, as well as of the factors that favor or hinder
      them. To the extent that research in this field progresses and effective
      interventions are identified, comprehensive patient care will be improved in
      consonance with the new directives for chronicity.

PMID- 24871113
TI  - [Spirometry quality in preschool children].
AB  - BACKGROUND: Carrying out quality spirometric maneuvers in preschool children in
      both the diagnosis and follow-up of respiratory diseases continues to be very
      scarce. This is due to several reasons, including a lack of consensus on quality
      criteria and the acceptability of the test. The purpose of this study is
      therefore to obtain reference norms from a population of healthy preschool
      children from the Autonomous Community of Navarre (Spain). METHOD: A total of 114
      healthy preschool children aged between 3 and 7 years of age, without prior
      experience in carrying out lung function tests, were included. RESULTS: A total
      of 76 were able to realize at least two acceptable spirometric maneuvers, and 60
      of them maneuvers that were acceptable and reproducible, according to ATS/ERS
      criteria. This represents a global success percentage of 59%. The most common
      failing was premature and brusque termination of the spirometric maneuver,
      followed by an inadequate peak in breathing. CONCLUSIONS: Over half of the
      preschool children were able to realize quality spirometric maneuvers. Our data
      make it possible to recommend the proposed quality criteria as being suitable for
      routine use, and to encourage the use of spirometry in regular clinical practice
      within the setting of specialized care.

PMID- 24871114
TI  - [Validity of airway predictors in outpatient medicine].
AB  - Isolation of the airway sometimes determines the survival or death of the
      patient. To anticipate the presence of a difficult airway (DA) there are a number
      of indicators that are validated for hospitals: Mallampati, sternum and
      thyromental distance, interdental distance and Cormack grade. The aim of this
      study is to evaluate the use of these indicators in the ambulatory setting and to
      know the incidence of DA. This data was collected from 324 intubations. Most
      patients were males (65.2%). The average age of the population was 63 years and
      no significant difference in age between DA and DA was found. A DA presence of
      20.7% was objectified and an alternative device utilization of 21.4%. The
      thyromental distance was abnormal in 59% of patients and sternomentonal distance
      in 56.4% but neither showed an association with the presence of DA (p = 0.681 and
      p = 0.415 respectively). Interdental distance was less than 3 cm if presence is
      associated with DA (p = 0.005). The sensitivity and specificity of all measures
      are low. According to our series the sternum and thyromental distance are not
      useful in the ambulatory setting, but interdental distance is useful for
      predicting a DA.

PMID- 24871115
TI  - [Acute poisoning in patients over 65 years of age].
AB  - BACKGROUND: There are few Spanish studies on acute poisoning in the elderly
      despite the associated risk factors of this group of patients. MATERIAL AND
      METHODS: Retrospective descriptive study of acute poisonings treated in the
      Emergency Service of the University Hospital of Zaragoza from 1995 to 2009 on
      patients 65 years old or older. RESULTS: A total of 762 patients were selected in
      the study (4.74% of all acute poisonings) with a mean age of 74.16 (SD +/- 6)
      years. Ingestion was the major route of exposure (85%) and alcohol overdose
      (28,7%) was the most frequent type of poisoning. A trend was also observed
      showing a lower emetic treatment and gastric lavage and an increase in activated
      charcoal. Benzodiazepines (14.3%) and toxic household products (11%) with caustic
      properties were also the main toxics found in the study. CONCLUSIONS: Acute
      poisonings in the elderly required more hospitalizations, have a higher mortality
      and more autolytic attempts which result in death.

PMID- 24871116
TI  - Diagnostic utility of oxidative damage markers for early rheumatoid arthritis in
      non-smokers and negative anti-CCP patients.
AB  - BACKGROUND: Besides the development of new markers and diagnostic criteria for
      rheumatoid arthritis (RA), many patients are still diagnosed after several years
      of symptoms. Oxidative stress markers are already increased at an early stage of
      RA. Our aim was to evaluate the additional diagnostic value of these markers.
      METHODS: A case-control study was performed. Patients met the 1987 RA ACR
      criteria, less than 2 years of symptoms and no previous treatment with disease
      modifying anti-rheumatic drugs (DMARD), steroids or vitamin E. Controls were
      selected from patient's relatives and matched (1:1) by gender, age, and current
      smoking habit. Oxidative damage markers were malonyldialdehyde (MDA), Lipid
      hydroperoxides (LOOH) and Carbonyl proteins (CP). Statistical analysis was
      performed in agreement with the STARD initiative. RESULTS: Sixty-five RA patients
      without treatment and 65 healthy controls were included. LOOH, CP, antibodies
      against citrullinated peptides (anti-CCP) and rheumatoid factor (RF) were
      significantly higher in patients, and MDA higher in controls. The same results
      were obtained in the subgroups of patients who smoke or not, and in anti-CCP
      positive or negative. The diagnosis performance of traditional markers showed
      good specificity but low sensitivity. The addition of LOOH and CP increased the
      sensitivity and the area under the receiving operating characteristic (ROC) curve
      especially in non-smoking (66%) and negative anti-CCP (51%) patients.
      CONCLUSIONS: The separate or combined addition of LOOH or CP to the traditional
      disease markers improved the diagnosis of RA, especially in non-smoking or
      negative anti-CCP patients.

PMID- 24871117
TI  - [Stroke mimics: a challenge for the emergency physician].
AB  - BACKGROUND: To study the number of patients diagnosed with a stroke in the
      emergency service of a first level hospital and the proportion of these patients
      who were finally stroke mimics, as well as to describe and analyze the variables
      that can help in differential diagnosis in hospital emergency services. METHOD:
      Nine month prospective study. All patients evaluated in emergency services and
      admitted with a diagnosis of stroke were included. Different clinical variables
      were analyzed that included prior history, history of the current event, general
      physical and neurological examination, NIHSS classification and Oxfordshire
      Community Stroke Project Classification. The final diagnosis was made by a panel
      of experts with access to clinical characteristics, image studies and other
      tests. The univariate and multivariate analysis determined the characteristics
      that help in distinguishing strokes from stroke mimics. RESULTS: One hundred and
      forty-four cases of stroke were registered; the final sample was made up of 140
      patients. The final diagnosis was stroke in 103 out of 140 (73.6%) and stroke
      mimic in the rest. Eleven variables predicted the diagnosis in patients with a
      suspected stroke: age over 70 years (p=0.012), NIHSS classification > 5, reaching
      a clinical classification (p=0.019) capable of determining the exact start
      (p=0.000), abnormal vascular findings (p=0.014), gaze deviation (p=0.042), sight
      loss (p=0.052) and extensor plantar response (p=0.025) favored diagnosis of
      stroke, while epileptic seizures (p=0.029), neurological symptoms not congruent
      with the vascular territory (p=0.022) and abnormal findings in other systems
      (p=0.14) favored diagnosis of stroke mimic. CONCLUSION: Stroke mimics constitute
      one-third of the patients admitted from emergency services as strokes, with a
      highly varied etiology. Achieving a suitable clinical history and a precise
      physical examination is of great importance and can help less experienced
      doctors.

PMID- 24871118
TI  - [Pluripotent stem cells on cell therapy].
AB  - Induced pluripotent stem (iPS) cells are a novel stem cell population derived
      from human somatic cells through reprogramming using a set of transcription
      factors. These iPS cells were shown to share the characteristics of embryonic
      stem cells, including the ability to give rise to differentiated cells of every
      tissue type of the body. In the shorter term, iPS cells will be useful for
      creating patient-identical disease model cells in which the pathological process
      can be studied and drugs can be tested. Despite critical attitudes, accumulating
      preclinical evidence supports the effectiveness of iPSC-based cell therapy on the
      selection of appropriate iPSC clones. The production of iPS cells has also
      spurred the development of other techniques, for example, transdifferentiation by
      researchers can now convert heart fibroblasts directly in vivo into myocytes by
      similar methods. This pluripotent cells is indeed of great value in medical
      research and it is opening new possibilities in cell therapy.

PMID- 24871119
TI  - [Paraganglioma of the cauda equina].

PMID- 24871120
TI  - [Variation of the characteristics and epidemiology of patients with pneumonia
      acquired in the community treated in hospital A and E services].

PMID- 24871121
TI  - [Variation of the characteristics and epidemiology of patients with pneumonia
      acquired in the community treated in hospital A and E services].

PMID- 24871122
TI  - [On carers of dependent people].

PMID- 24871123
TI  - [Cystic tumors in the retrorectal space. Do these two cases have something in
      common?].
AB  - Cystic lesions in the retrorectal or presacral space present a broad differential
      diagnosis. Rare but typical lesions at this site are those related to embryonic
      development, which are the most frequent presacral congenital lesions in adults.
      Amongst these tumors, epidermoid cysts and cystic hamartomas are the most common
      lesions. Cystic masses, which are asymptomatic in approximately 50% of the cases
      at diagnosis, may show complications such as infection or malignant degeneration.
      Initial diagnosis is based on imaging techniques although definite lesion
      characterization, essential due to their malignancy risk, is given by the
      pathological analysis of the surgical piece.

PMID- 24871124
TI  - [Chronic intestinal pseudo-obstruction due to intestinal neuronal dysplasia type
      B (IND B), concerning one case].
AB  - Intestinal neuronal dysplasia type B (IND B) is an infrequent disease due to
      hyperplasia of the parasympathetic submucous plexus which causes alteration of
      intestinal motility, giving rise to symptoms of constipation and subocclusive
      manifestations. The disease is difficult to diagnose. It requires high clinical
      suspicion and should include differential diagnosis of patients with repeated
      subocclusive manifestations in order to make an early and correct diagnosis and
      avoid complications derived from unnecessary surgery that worsens the prognosis.
      We present the case of a 33-year-old Moroccan male who was admitted to our
      hospital on 2 occasions in 11 months, requiring total parenteral nutrition (TPN)
      for five months. The immunohistochemical analysis of the ileostomy and colostomy
      stoma led to a diagnosis of IND B. Eighteen months later, the patients is leading
      a normal life and has recovered the 25 kilos lost following the dietary
      indications and with the enzymatic supplements.

PMID- 24871125
TI  - [Langerhans cell histiocytosis].
AB  - We describe the case of male diagnosed with histiocytosis of Langerhans cells.
      Histiocytosis X is an interstitial disease with a real incidence and an unknown
      prevalence that can be suspected due to epidemiological and radiological data.
      The diagnosis can be realized using BAL and/or anatomo-pathological study of a
      biopsy. The principal treatment is to give up the tobacco habit. Evolution can be
      favourable. 

PMID- 24871126
TI  - [Splenic disorders in internal medicines].
AB  - The spleen is the largest lymphopoietic organ, containing 25% of total lymphoid
      mass. It participates in cellular and humoral immunity and intervenes in the
      renovation of red cells and the elimination of bacteria. Splenic functions are
      reduced when the spleen is absent, which entails, amongst other complications,
      greater susceptibility to suffering from sepsis due to encapsulated organisms. We
      present 6 clinical cases admitted to the Internal Medicine serve with splenic
      pathology and we make a review of the approach to be used. The spectrum of
      splenic lesions in internal medicine is very wide. On occasions, a splenic
      pathology can be suspected due to clinical history, physical exploration or
      because of cytopenias in the analyses. Different complementary tests are
      available for completing study of these lesions. A splenectomy can be carried out
      in case of diagnostic doubt, with the most frequent diagnoses being hepatic
      cirrhosis and lymphoma/leukaemia.

PMID- 24871127
TI  - Characterisation and antimicrobial activity of the volatile components of the
      flowers of Magydaris tomentosa (Desf.) DC. collected in Sicily and Algeria.
AB  - The essential oils of the flowers of Magydaris tomentosa (Desf.) DC. (Apiaceae)
      collected in Sicily (MSi) and Algeria (MAl), respectively, were obtained by
      hydrodistillation, and their compositions were analysed. The analyses allowed the
      identification and quantification of 23 components in MSi and 60 compounds in
      MAl, respectively, showing a very different profile in the composition of the two
      populations. The main components of MSi were cembrene (28.2%), alpha-springene
      (17.5%) and beta-springene (14.8%), also present in MAl but in lesser amount
      (0.4%, 1.8% and 0.9%, respectively), whereas the principal constituents of MAl
      were (E)-nerolidol (35.4%), alpha-costol (13.3%) and beta-costol (6.8%). Both MSi
      and MAl exhibited a significant antibacterial activity against Staphylococcus
      epidermidis (minimum inhibitory concentration = 25 and 12.5 MUg/mL,
      respectively). The chemotaxonomy markers of the species were identified.

PMID- 24871128
TI  - Driving convergence with human diversity.
AB  - Convergent science will require human diversity-individuals with different
      backgrounds and life experiences-to drive it forward. 

PMID- 24871129
TI  - Tumor archaeology: tracking leukemic evolution to its origins.
AB  - Unearthing of the BRAF mutation in self-renewing hematopoietic stem cells reveals
      an unexpected origin for hairy cell leukemia-a mature B cell malignancy-and a
      potential new therapeutic target (Chung et al., this issue). 

PMID- 24871130
TI  - Photoactivation of endogenous latent transforming growth factor-beta1 directs
      dental stem cell differentiation for regeneration.
AB  - Rapid advancements in the field of stem cell biology have led to many current
      efforts to exploit stem cells as therapeutic agents in regenerative medicine.
      However, current ex vivo cell manipulations common to most regenerative
      approaches create a variety of technical and regulatory hurdles to their clinical
      translation, and even simpler approaches that use exogenous factors to
      differentiate tissue-resident stem cells carry significant off-target side
      effects. We show that non-ionizing, low-power laser (LPL) treatment can instead
      be used as a minimally invasive tool to activate an endogenous latent growth
      factor complex, transforming growth factor-beta1 (TGF-beta1), that subsequently
      differentiates host stem cells to promote tissue regeneration. LPL treatment
      induced reactive oxygen species (ROS) in a dose-dependent manner, which, in turn,
      activated latent TGF-beta1 (LTGF-beta1) via a specific methionine residue (at
      position 253 on LAP). Laser-activated TGF-beta1 was capable of differentiating
      human dental stem cells in vitro. Further, an in vivo pulp capping model in rat
      teeth demonstrated significant increase in dentin regeneration after LPL
      treatment. These in vivo effects were abrogated in TGF-beta receptor II (TGF
      betaRII) conditional knockout (DSPP(Cre)TGF-betaRII(fl/fl)) mice or when wild
      type mice were given a TGF-betaRI inhibitor. These findings indicate a pivotal
      role for TGF-beta in mediating LPL-induced dental tissue regeneration. More
      broadly, this work outlines a mechanistic basis for harnessing resident stem
      cells with a light-activated endogenous cue for clinical regenerative
      applications. 

PMID- 24871131
TI  - Improved survival with T cell clonotype stability after anti-CTLA-4 treatment in
      cancer patients.
AB  - Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) blockade can promote
      antitumor T cell immunity and clinical responses. The mechanism by which anti
      CTLA-4 antibodies induces antitumor responses is controversial. To determine the
      effects of CTLA-4 blockade on the T cell repertoire, we used next-generation deep
      sequencing to measure the frequency of individual rearranged T cell receptor beta
      (TCRbeta) genes, thereby characterizing the diversity of rearrangements, known as
      T cell clonotypes. CTLA-4 blockade in patients with metastatic castration
      resistant prostate cancer and metastatic melanoma resulted in both expansion and
      loss of T cell clonotypes, consistent with a global turnover of the T cell
      repertoire. Overall, this treatment increased TCR diversity as reflected in the
      number of unique TCR clonotypes. The repertoire of clonotypes continued to evolve
      over subsequent months of treatment. Whereas the number of clonotypes that
      increased with treatment was not associated with clinical outcome, improved
      overall survival was associated with maintenance of high-frequency clones at
      baseline. In contrast, the highest-frequency clonotypes fell with treatment in
      patients with short overall survival. Stably maintained clonotypes included T
      cells having high-avidity TCR such as virus-reactive T cells. Together, these
      results suggest that CTLA-4 blockade induces T cell repertoire evolution and
      diversification. Moreover, improved clinical outcomes are associated with less
      clonotype loss, consistent with the maintenance of high-frequency TCR clonotypes
      during treatment. These clones may represent the presence of preexisting high
      avidity T cells that may be relevant in the antitumor response. 

PMID- 24871133
TI  - CD4 T cells with effector memory phenotype and function develop in the sterile
      environment of the fetus.
AB  - The T cell compartment is considered to be naive and dedicated to the development
      of tolerance during fetal development. We have identified and characterized a
      population of fetally developed CD4 T cells with an effector memory phenotype
      (TEM), which are present in cord blood. This population is polyclonal and has
      phenotypic features similar to those of conventional adult memory T cells, such
      as CD45RO expression. These cells express low levels of CD25 but are distinct
      from regulatory T cells because they lack Foxp3 expression. After T cell receptor
      activation, neonatal TEM cells readily produced tumor necrosis factor-alpha (TNF
      alpha) and granulocyte-macrophage colony-stimulating factor (GM-CSF). We also
      detected interferon-gamma (IFN-gamma)-producing T helper 1 (TH1) cells and
      interleukin-4 (IL-4)/IL-13-producing TH2-like cells, but not IL-17-producing
      cells. We used chemokine receptor expression patterns to divide this TEM
      population into different subsets and identified distinct transcriptional
      programs using whole-genome microarray analysis. IFN-gamma was found in CXCR3(+)
      TEM cells, whereas IL-4 was found in both CXCR3(+) TEM cells and CCR4(+) TEM
      cells. CCR6(+) TEM cells displayed a genetic signature that corresponded to TH17
      cells but failed to produce IL-17A. However, the TH17 function of TEM cells was
      observed in the presence of IL-1beta and IL-23. In summary, in the absence of
      reported pathology or any major infectious history, T cells with a memory-like
      phenotype develop in an environment thought to be sterile during fetal
      development and display a large variety of inflammatory effector functions
      associated with CD4 TH cells at birth. 

PMID- 24871132
TI  - Hematopoietic stem cell origin of BRAFV600E mutations in hairy cell leukemia.
AB  - Hairy cell leukemia (HCL) is a chronic lymphoproliferative disorder characterized
      by somatic BRAFV600E mutations. The malignant cell in HCL has immunophenotypic
      features of a mature B cell, but no normal counterpart along the continuum of
      developing B lymphocytes has been delineated as the cell of origin. We find that
      the BRAFV600E mutation is present in hematopoietic stem cells (HSCs) in HCL
      patients, and that these patients exhibit marked alterations in hematopoietic
      stem/progenitor cell (HSPC) frequencies. Quantitative sequencing analysis
      revealed a mean BRAFV600E-mutant allele frequency of 4.97% in HSCs from HCL
      patients. Moreover, transplantation of BRAFV600E-mutant HSCs from an HCL patient
      into immunodeficient mice resulted in stable engraftment of BRAFV600E-mutant
      human hematopoietic cells, revealing the functional self-renewal capacity of HCL
      HSCs. Consistent with the human genetic data, expression of BRafV600E in murine
      HSPCs resulted in a lethal hematopoietic disorder characterized by splenomegaly,
      anemia, thrombocytopenia, increased circulating soluble CD25, and increased
      clonogenic capacity of B lineage cells-all classic features of human HCL. In
      contrast, restricting expression of BRafV600E to the mature B cell compartment
      did not result in disease. Treatment of HCL patients with vemurafenib, an
      inhibitor of mutated BRAF, resulted in normalization of HSPC frequencies and
      increased myeloid and erythroid output from HSPCs. These findings link the
      pathogenesis of HCL to somatic mutations that arise in HSPCs and further suggest
      that chronic lymphoid malignancies may be initiated by aberrant HSCs. 

PMID- 24871134
TI  - Variability in size-selective mortality obscures the importance of larval traits
      to recruitment success in a temperate marine fish.
AB  - In fishes, the growth-mortality hypothesis has received broad acceptance as a
      driver of recruitment variability. Recruitment is likely to be lower in years
      when the risk of starvation and predation in the larval stage is greater, leading
      to higher mortality. Juvenile snapper, Pagrus auratus (Sparidae), experience high
      recruitment variation in Port Phillip Bay, Australia. Using a 5-year (2005, 2007,
      2008, 2010, 2011) data set of larval and juvenile snapper abundances and their
      daily growth histories, based on otolith microstructure, we found selective
      mortality acted on larval size at 5 days post-hatch in 4 low and average
      recruitment years. The highest recruitment year (2005) was characterised by no
      size-selective mortality. Larval growth of the initial larval population was
      related to recruitment, but larval growth of the juveniles was not. Selective
      mortality may have obscured the relationship between larval traits of the
      juveniles and recruitment as fast-growing and large larvae preferentially
      survived in lower recruitment years and fast growth was ubiquitous in high
      recruitment years. An index of daily mortality within and among 3 years (2007,
      2008, 2010), where zooplankton were concurrently sampled with ichthyoplankton,
      was related to per capita availability of preferred larval prey, providing
      support for the match-mismatch hypothesis. In 2010, periods of low daily
      mortality resulted in no selective mortality. Thus both intra- and inter-annual
      variability in the magnitude and occurrence of selective mortality in species
      with complex life cycles can obscure relationships between larval traits and
      population replenishment, leading to underestimation of their importance in
      recruitment studies.

PMID- 24871135
TI  - Shrubs as ecosystem engineers across an environmental gradient: effects on
      species richness and exotic plant invasion.
AB  - Ecosystem-engineering plants modify the physical environment and can increase
      species diversity and exotic species invasion. At the individual level, the
      effects of ecosystem engineers on other plants often become more positive in
      stressful environments. In this study, we investigated whether the community
      level effects of ecosystem engineers also become stronger in more stressful
      environments. Using comparative and experimental approaches, we assessed the
      ability of a native shrub (Ericameria ericoides) to act as an ecosystem engineer
      across a stress gradient in a coastal dune in northern California, USA. We found
      increased coarse organic matter and lower wind speeds within shrub patches.
      Growth of a dominant invasive grass (Bromus diandrus) was facilitated both by
      aboveground shrub biomass and by growing in soil taken from shrub patches.
      Experimental removal of shrubs negatively affected species most associated with
      shrubs and positively affected species most often found outside of shrubs.
      Counter to the stress-gradient hypothesis, the effects of shrubs on the physical
      environment and individual plant growth did not increase across the established
      stress gradient at this site. At the community level, shrub patches increased
      beta diversity, and contained greater rarified richness and exotic plant cover
      than shrub-free patches. Shrub effects on rarified richness increased with
      environmental stress, but effects on exotic cover and beta diversity did not. Our
      study provides evidence for the community-level effects of shrubs as ecosystem
      engineers in this system, but shows that these effects do not necessarily become
      stronger in more stressful environments. 

PMID- 24871136
TI  - Coordination reaction between tetraphenylporphyrin and nickel on a TiO2(110)
      surface.
AB  - In situ metalation of tetraphenylporphyrin (2HTPP) (sub)monolayers with Ni on a
      TiO2(110) surface to nickel(II)-tetraphenylporphyrin (NiTPP) depends on
      temperature and order of deposition, and affects conformation and bonding
      geometry of the porphyrin.

PMID- 24871137
TI  - The reversible anomalous high lithium capacity of MnO2 nanowires.
AB  - MnO2 as a material for supercapacitors is generally predicted to insert only one
      cation per unit cell. However, it is shown here to reversibly insert more than
      one cation in an organic electrolyte; however, in an aqueous electrolyte, the
      insertion ion is actually shown to be a combination of protons and cations. 

PMID- 24871138
TI  - Minimal role of eastern fence lizards in Borrelia burgdorferi transmission in
      central New Jersey oak/pine woodlands.
AB  - The eastern fence lizard, Sceloporus undulatus , is widely distributed in eastern
      and central North America, ranging through areas with high levels of Lyme
      disease, as well as areas where Lyme disease is rare or absent. We studied the
      potential role of S. undulatus in transmission dynamics of Lyme spirochetes by
      sampling ticks from a variety of natural hosts at field sites in central New
      Jersey, and by testing the reservoir competence of S. undulatus for Borrelia
      burgdorferi in the laboratory. The infestation rate of ticks on fence lizards was
      extremely low (prevalence = 0.087, n = 23) compared to that on white-footed mice
      and other small mammals (prevalence = 0.53, n = 140). Of 159 nymphs that had fed
      as larvae on lizards that had previously been exposed to infected nymphs, none
      was infected with B. burgdorferi , compared with 79.9% of 209 nymphs that had fed
      as larvae on infected control mice. Simulations suggest that changes in the
      numbers of fence lizards in a natural habitat would have little effect on the
      infection rate of nymphal ticks with Lyme spirochetes. We conclude that in
      central New Jersey, S. undulatus plays a minimal role in the enzootic
      transmission cycle of Lyme spirochetes. 

PMID- 24871139
TI  - Surgical management of trigeminal neuralgia: use and cost-effectiveness from an
      analysis of the Medicare Claims Database.
AB  - BACKGROUND: Trigeminal neuralgia is a relatively common neurosurgical pathology
      with multiple management options. Microvascular decompression (MVD) is
      nonablative and is considered the gold standard. However, stereotaxic
      radiosurgery (SRS) and percutaneous stereotaxic rhizotomy (PSR) are 2 noninvasive
      but ablative options that have rapidly gained support. OBJECTIVE: To use Medicare
      claims data in conjunction with a literature review to assess the usage,
      effectiveness, and cost-effectiveness of the 3 different invasive treatments for
      trigeminal neuralgia. METHODS: All of the claims of trigeminal neuralgia
      treatment were extracted from the 2011 5% Inpatient and Outpatient Limited Data
      Set. Current Procedural Terminology, 4th Edition/International Classification of
      Diseases, Ninth Revision codes for the 3 different surgical treatment modalities
      were used to further classify these claims. Kaplan-Meier survival curves in key
      articles were used to calculate quality-adjusted life years and cost
      effectiveness for each procedure. RESULTS: A total of 1582 claims of trigeminal
      neuralgia were collected. Ninety-four (6%) patients underwent surgical
      intervention. Forty-eight (51.1%) surgical patients underwent MVD, 39 (41.5%)
      underwent SRS, and 7 (7.4%) underwent PSR. The average weighted costs for MVD,
      SRS, and PSR were $40 434.95, $38 062.27, and $3910.64, respectively. The quality
      adjusted life years were 8.2 for MVD, 4.9 for SRS, and 6.5 for PSR. The cost per
      quality-adjusted life year was calculated as $4931.1, $7767.8, and $601.64 for
      MVD, SRS, and PSR, respectively. CONCLUSION: This study shows that the most
      frequently used surgical management of trigeminal neuralgia is MVD, followed
      closely by SRS. PSR, despite being the most cost-effective, is by far the least
      utilized treatment modality.

PMID- 24871140
TI  - Pipeline embolization device for the treatment of intra- and extracranial
      fusiform and dissecting aneurysms: initial experience and long-term follow-up.
AB  - BACKGROUND: Flow-diverting stents offer a promising treatment option for complex
      aneurysms. OBJECTIVE: To evaluate the safety and efficacy of the Pipeline
      embolization device (PED) in the treatment of fusiform and dissecting aneurysms.
      METHODS: Sixty-five consecutive patients with 69 fusiform and dissecting
      aneurysms underwent endovascular treatment with the use of the PED. Target
      vessels included the internal carotid artery (n = 28), middle cerebral artery (n
      = 2), anterior cerebral artery (n = 1), vertebral artery (n = 20), basilar artery
      (n = 17), and posterior cerebral artery (n = 1). An average of 3.0 PEDs per
      target vessel were deployed. RESULTS: Exclusion of the aneurysm(s) immediately
      after PED deployment was not observed. Angiographic follow-up examinations were
      performed in 63/65 patients (67/69 lesions). They showed complete cure of the
      target lesion in the first follow-up angiography (3.4 months mean interval) in 24
      (36%) cases, partial elimination in 30 (45%), and no improvement in 13 (19%).
      After the latest follow-up (>1 digital subtraction angiography, n = 49, 27.4
      months mean interval) complete cure of the target lesion was observed in 33
      (67%), partial elimination in 14 (29%), and no change in 2 (4%). Taking all
      follow-up examinations together, 39/67 (58%) aneurysms were cured. The morbidity
      and mortality in the entire series were 5% and 8%, respectively. CONCLUSION: Flow
      diverters offer a promising treatment option in fusiform and dissecting
      aneurysms. The introduction of flow diverters with different densities might help
      to identify the optimal amount of coverage needed given different anatomic
      presentations of fusiform and dissecting aneurysms.

PMID- 24871141
TI  - Platinum-iridium subdermal magnetic resonance imaging-compatible needle
      electrodes are suitable for intraoperative neurophysiological monitoring during
      image-guided surgery with high-field intraoperative magnetic resonance imaging:
      an experimental study.
AB  - BACKGROUND: Neurosurgery aims to achieve maximal tumor resection while preserving
      neurological function. Tools such as neuronavigation, high-field intraoperative
      magnetic resonance imaging (iMRI), and intraoperative neurophysiological
      monitoring (IOM) have consistently helped to achieve this goal, but integration
      has often been difficult. Surgery of eloquent areas requires IOM, which in an
      operating theater equipped with high-field (1.5-T) iMRI could present several
      issues. OBJECTIVE: To identify the electrodes types more suitable for IOM in a
      high-field iMRI operating theater by performing an experimental study on
      phantoms, to report our experience with platinum-iridium (Pt/Ir) electrodes
      during surgery, and to prove that integration between IOM with Pt/Ir electrodes
      and high-field iMRI is safe and reliable. METHODS: Electrodes of different
      materials (gold, Pt/Ir, and stainless steel) were tested on jelly phantom and
      apples to evaluate their safety and compatibility. Subsequently, electrodes were
      tested on 5 healthy volunteers before being used on patients. RESULTS: None of
      the different electrodes presented thermal instability, and no damage to the
      volunteers' skin occurred. Stainless steel electrodes caused severe imaging
      distortion. Gold electrodes had no distortion, but their high cost makes their
      use in routine surgery unaffordable. Pt/Ir electrodes are significantly less
      expensive than gold electrodes and were completely safe, compatible, and suitable
      for use in an operating theater with high-field iMRI, providing excellent IOM and
      mild interference that did not affect the quality of intraoperative imaging.
      CONCLUSION: We suggest the use of Pt/Ir electrodes for IOM in 1.5-T iMRI suites.
      ABBREVIATIONS: DTI, diffusion tensor imagingiMRI, intraoperative magnetic
      resonance imagingIOM, intraoperative neurophysiological monitoring.

PMID- 24871142
TI  - Effects of an immunomodulatory therapy and chondroitinase after spinal cord
      hemisection injury.
AB  - BACKGROUND: Individually, immunomodulatory therapy and chondroitinases have
      demonstrated neuroprotective and potential neuroregenerative effects following
      spinal cord injury. OBJECTIVE: To investigate the therapeutic potential of
      combined immunomodulatory and chondroitin sulfate-glycosaminoglycan degradation
      therapy in spinal cord injury. METHODS: A combined immunomodulatory treatment
      using (1) liposome-encapsulated clodronate (selectively depletes peripheral
      macrophages), and (2) rolipram (a selective type 4 phosphodiesterase inhibitor),
      along with the chondroitin sulfate proteoglycan-glycosaminoglycan-degrading
      enzyme, chondroitinase ABC (ChABC), was assessed for its potential to promote
      axonal regrowth and improve locomotor recovery following midthoracic spinal cord
      hemisection injury in adult rats. RESULTS: We demonstrate that combined treatment
      with liposomal clodronate, rolipram, and ChABC attenuates macrophage accumulation
      at the site of injury, reduces axonal die-back of injured dorsal column axons,
      and produces the greatest improvement in locomotor recovery at 6 weeks postinjury
      compared with controls and noncombined therapy. Anterograde and retrograde
      tracing revealed that delivery of clodronate, rolipram, and ChABC did not promote
      substantial axonal regeneration through the site of injury, although the
      treatment did limit the extent of axonal die-back. Histological assessments
      revealed that combined treatment with clodronate/rolipram and/or ChABC resulted
      in a significant reduction in lesion size and cystic cavitation in comparison
      with injured controls. Combined clodronate, rolipram, and ChABC treatment reduced
      the accumulation of macrophages within the injured spinal cord 7 weeks after
      injury. CONCLUSION: The present data suggest that delivery of an immunomodulatory
      therapy consisting of clodronate and rolipram, in combination with ChABC, reduces
      axonal injury and enhances neuroprotection, plasticity, and hindlimb functional
      recovery after hemisection spinal cord injury in adult rats.

PMID- 24871144
TI  - Twenty-year follow-up of flow reversal and revascularization for a giant
      serpentine basilar artery aneurysm.
AB  - BACKGROUND AND IMPORTANCE: Current microsurgical and endovascular therapies have
      offered little advancement for the treatment of complex vertebrobasilar
      aneurysms. The outcome of patients with these rare lesions has remained poor,
      despite sometimes heroic measures. CLINICAL PRESENTATION: The authors report a
      case of a 65-year-old man who 20 years earlier had presented with symptoms
      suggestive of brainstem compression. Imaging at the time revealed a giant,
      serpentine aneurysm of the basilar artery. The patient was treated with
      superficial temporal artery to superior cerebellar artery bypass and
      decompression of the aneurysm contents. Twenty years after this treatment, the
      patient remains functionally intact with few sequelae from his treatment or the
      pathology. Follow-up imaging reveals thrombosis of the aneurysm without ischemic
      damage to the brainstem. CONCLUSION: This case demonstrates that good functional
      outcomes are possible for select complex posterior circulation aneurysms by using
      flow reversal and revascularization; however, at this time, we are unable to
      predict for which patients this strategy will be successful.

PMID- 24871143
TI  - Comparison of plan quality and delivery time between volumetric arc therapy
      (RapidArc) and Gamma Knife radiosurgery for multiple cranial metastases.
AB  - BACKGROUND: Volumetric modulated arc therapy (VMAT) has been shown to be feasible
      for radiosurgical treatment of multiple cranial lesions with a single isocenter.
      OBJECTIVE: To investigate whether equivalent radiosurgical plan quality and
      reduced delivery time could be achieved in VMAT for patients with multiple
      intracranial targets previously treated with Gamma Knife (GK) radiosurgery.
      METHODS: We identified 28 GK treatments of multiple metastases. These were
      replanned for multiarc and single-arc, single-isocenter VMAT (RapidArc) in
      Eclipse. The prescription for all targets was standardized to 18 Gy. Each plan
      was normalized for 100% prescription dose to 99% to 100% of target volume. Plan
      quality was analyzed by target conformity (Radiation Therapy Oncology Group and
      Paddick conformity indices [CIs]), dose falloff (area under the dose-volume
      histogram curve), as well as the V4.5, V9, V12, and V18 isodose volumes. Other
      end points included beam-on and treatment time. RESULTS: Compared with GK,
      multiarc VMAT improved median plan conformity (CIVMAT = 1.14, CIGK = 1.65; P <
      .001) with no significant difference in median dose falloff (P = .269), 12 Gy
      isodose volume (P = .500), or low isodose spill (P = .49). Multiarc VMAT plans
      were associated with markedly reduced treatment time. A predictive model of the
      12 Gy isodose volume as a function of tumor number and volume was also developed.
      CONCLUSION: For multiple target stereotactic radiosurgery, 4-arc VMAT produced
      clinically equivalent conformity, dose falloff, 12 Gy isodose volume, and low
      isodose spill, and reduced treatment time compared with GK. Because of its
      similar plan quality and increased delivery efficiency, single-isocenter VMAT
      radiosurgery may constitute an attractive alternative to multi-isocenter
      radiosurgery for some patients.

PMID- 24871146
TI  - The anterior transcallosal approach to a cerebral aqueduct tumor: a 3-dimensional
      operative video.

PMID- 24871145
TI  - Subtemporal-medial transpetrous (Kawase) approach for anterior inferior
      cerebellar artery aneurysm clipping: operative 3-dimensional video.

PMID- 24871147
TI  - Intracranial pressure modulates distortion product otoacoustic emissions: a proof
      of-principle study.
AB  - BACKGROUND: There is an important need to develop a noninvasive method for
      assessing intracranial pressure (ICP). We report a novel approach for monitoring
      ICP using cochlear-derived distortion product otoacoustic emissions (DPOAEs),
      which are affected by ICP. OBJECTIVE: We hypothesized that changes in ICP may be
      reflected by altered DPOAE responses via an associated change in perilymphatic
      pressure. METHODS: We measured the ICP and DPOAEs (magnitude and phase angle)
      during opening and closing in 20 patients undergoing lumbar puncture. RESULTS: We
      collected data on 18 patients and grouped them based on small (<4 mm Hg), medium
      (5-11 mm Hg), or large (>=15 mm Hg) ICP changes. A permutation test was applied
      in each group to determine whether changes in DPOAEs differed from zero when ICP
      changed. We report significant changes in the DPOAE magnitudes and angles,
      respectively, for the group with the largest ICP changes and no changes for the
      group with the smallest changes; the group with medium changes had variable DPOAE
      changes. CONCLUSION: We report, for the first time, systematic changes in DPOAE
      magnitudes and phase in response to acute ICP changes. Future studies are
      warranted to further develop this new approach. ABBREVIATIONS: DPOAE, distortion
      product otoacoustic emissionICP, intracranial pressureIIH, idiopathic
      intracranial hypertensionLP, lumbar punctureTBI, traumatic brain injury.

PMID- 24871149
TI  - Validity of International Classification of Diseases, Ninth Revision, Clinical
      Modification (ICD-9-CM) screening for sepsis in surgical mortalities.
AB  - BACKGROUND: Sepsis is among the leading causes of death in the United States. The
      Agency for Healthcare Research and Quality uses International Classification of
      Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) billing code screening
      for the identification of sepsis. We investigated the incidence of sepsis in
      mortality at our academic medical center through ICD-9-CM screening of billing
      codes corresponding to sepsis and compared this approach for accuracy using
      physician chart review as the gold-standard. METHODS: Two hundred forty-three
      surgical mortalities between January 2012 and January 2013 were reviewed by a
      Performance Improvement team. All mortalities were screened and evaluated for
      sepsis using physician chart review and ICD-9-CM codes for sepsis (995.91),
      severe sepsis (995.92), and septic shock (785.52). RESULTS: Unexpected
      mortalities were associated with higher rates of sepsis and expected mortalities
      than anticipated (p<0.0001). A total of 40.6% of patients with sepsis suffered
      from more than one infection; the most common infectious sources were intra
      abdominal (43.5%), blood stream (40.3%), and pulmonary (38.7%) infections.
      Screening by ICD-9-CM identified sepsis in 23.0% of mortalities, and physician
      review identified sepsis in 25.5% of mortalities. The sensitivity and specificity
      of ICD-9-CM screening were 82.3% and 78.3%, respectively. The positive and
      negative predictive values were 91.1% and 62.1%, respectively. CONCLUSION: Sepsis
      is a common concurrent condition in surgical patients who die unexpectedly.
      Screening by ICD-9-CM for sepsis is accurate in identifying patients with sepsis
      but misses the identification of all patients with sepsis. The diagnostic
      accuracy of ICD-9-CM screening for sepsis is currently not adequate for public
      reporting or benchmarking, and is useful only as a guide for institutional
      quality improvement.

PMID- 24871148
TI  - Symptomatic thoracic spinal cord herniation: case series and technical report.
AB  - BACKGROUND AND IMPORTANCE: Idiopathic spinal cord herniation (ISCH) is an
      uncommon condition located predominantly in the thoracic spine and often
      associated with a remote history of a major traumatic injury. ISCH has an
      incompletely described presentation and unknown etiology. There is no consensus
      on the treatment algorithm and surgical technique, and there are few data on
      clinical outcomes. CLINICAL PRESENTATION: In this case series and technical
      report, we describe the atypical myelopathy presentation, remote history of
      traumatic injury, radiographic progression, treatment, and outcomes of 5 patients
      treated at Washington University for symptomatic ISCH. A video showing surgical
      repair is presented. In contrast to classic compressive myelopathy
      symptomatology, ISCH patients presented with an atypical myelopathy,
      characterized by asymmetric motor and sensory deficits and early-onset urinary
      incontinence. Clinical deterioration correlated with progressive spinal cord
      displacement and herniation observed on yearly spinal imaging in a patient imaged
      serially because of multiple sclerosis. Finally, compared with compressive
      myelopathy in the thoracic spine, surgical treatment of ISCH led to rapid
      improvement despite a long duration of symptoms. CONCLUSION: Symptomatic ISCH
      presents with atypical myelopathy and slow temporal progression and can be
      successfully managed with surgical repair.

PMID- 24871150
TI  - Marine and inland fishes of St. Croix, U. S. Virgin Islands: an annotated
      checklist.
AB  - An historical account is given for the ichthyological research at St. Croix, U.
      S. Virgin Islands, followed by an annotated list of 544 species of mostly marine
      shore fishes known or reported from the island to depths of 200 m. Color
      photographs are included for 103 of these species. Collections made at Buck
      Island Reef National Monument with the ichthyocide rotenone in 2001 and 2005
      increased the known ichthyofauna by about 80 species. The rational for inclusion
      of each species in the checklist is given, with remarks for those species for
      which additional documentation or voucher specimens are needed. Reports of
      species known or presumed to have been based on misidentifications are discussed.
      Of the total marine fish fauna of the island, 404 species (75%) are restricted to
      the western Atlantic Ocean, (223 of these species are essentially Caribbean
      endemics that do not occur south of the Amazon River outflow), and no St. Croix
      endemic species are known. An additional 17 species (3.2%) also occur at mid
      Atlantic islands, 57 species (10.6 %) are limited to both sides of the Atlantic
      Ocean, and 40 species (7.4%) have circumtropical distributions. The four most
      species-rich families are the Gobiidae (47 species), Serranidae (groupers and sea
      basses, 41), Labridae (wrasses and parrotfishes, 31), and Labrisomidae (scaly
      blennies, 27). Literature reports of Mosquitofish, Gambusia sp., from St. Croix
      apparently were based on misidentifications of a different introduced poeciliid
      genus. Four species of the amphidromus goby genus Sicydium occur in St. Croix
      inland waters, together with three established introduced species (one cichlid
      and two poeciliids). Also included are one catfish (Ictaluridae) and three
      sunfishes (Centrarchidae) known only from ponds. The Lionfish, Pterois volitans,
      the only introduced marine species, was first reported from St. Croix in 2008 and
      is now common despite control efforts. 

PMID- 24871151
TI  - An illustrated catalogue of the scalpellid barnacles (Crustacea: Cirripedia:
      Scalpellidae) collected during the HMS "challenger" expedition and deposited in
      the Natural History Museum, London.
AB  - For the first time since 1883, the "Challenger" collection of scalpellids stored
      in the Natural History Museum (London) and studied by Hoek, has been reviewed. It
      comprises 40 species now assigned to 17 genera and three subfamilies within the
      family Scalpellidae. A checklist of published records, type status, sources of
      supplementary descriptive information, updated distributions and known depth
      records is given. New photographs are included which may be useful for species
      identification and for any future systematic rearrangement of the scalpellids.
      Trianguloscalpellum weltnerianum (Pilsbry, 1911) is recognised as a junior
      subjective synonym of Trianguloscalpellum album (Hoek, 1883). 

PMID- 24871152
TI  - Diversity of sponges (Porifera) from cryptic habitats on the Belize barrier reef
      near Carrie Bow Cay.
AB  - The Caribbean barrier reef near Carrie Bow Cay, Belize, has been a focus of
      Smithsonian Institution (Washington) reef and mangrove investigations since the
      early 1970s. Systematics and biology of sponges (Porifera) were addressed by
      several researchers but none of the studies dealt with cryptic habitats, such as
      the shaded undersides of coral rubble, reef crevices, and caves, although a high
      species diversity was recognized and samples were taken for future reference and
      study. This paper is the result of processing samples taken between 1972 and
      2012. In all, 122 species were identified, 14 of them new (including one new
      genus). The new species are Tetralophophora (new genus) mesoamericana, Geodia
      cribrata, Placospongia caribica, Prosuberites carriebowensis, Timea diplasterina,
      Timea oxyasterina, Rhaphidhistia belizensis, Wigginsia curlewensis, Phorbas
      aurantiacus, Myrmekioderma laminatum, Niphates arenata, Siphonodictyon occultum,
      Xestospongia purpurea, and Aplysina sciophila. We determined that about 75 of the
      122 cryptic sponge species studied (61%) are exclusive members of the sciophilic
      community, 47 (39 %) occur in both, light-exposed and shaded or dark habitats.
      Since we estimate the previously known sponge population of Carrie Bow reefs and
      mangroves at about 200 species, the cryptic fauna makes up 38 % of total
      diversity. 

PMID- 24871153
TI  - Taxonomy, bionomics and faunistics of the nominate subgenus of Mylabris
      Fabricius, 1775, with the description of five new species (Coleoptera: Meloidae:
      Mylabrini).
AB  - The nominate subgenus of the mylabrine genus Mylabris is revised: five new
      species, M. (M.) alpicola sp.n., M. (M.) cernyi sp.n., M. (M.) mediorientalis
      sp.n., and M. (M.) pseudoemiliae sp.n., are described and figured; M. (M.)
      apiceguttata sp.n., is provisionally refered to the nominate subgenus. M. (M.)
      rishwani Makhan, 2012 is synonymized with M. (M.) quadripunctata (Linnaeus,
      1767). The other 20 species are characterized by short descriptions and figures,
      and a key to the species is provided. Tentatively, M. barezensis  and M.
      batnensis are placed in the nominate subgenus. The bionomics of the species is
      summarized in tables including information on phenology, elevation, habitat
      preference, host plants, larval biology, and host insects. Zoogeographic analysis
      of the subgenus was carried out on the basis of all available faunistic records
      from literature and collections which are summarized in Appendix. 

PMID- 24871154
TI  - Conspectus of the Phlaeothripinae genera from China and Southeast Asia
      (Thysanoptera, Phlaeothripidae).
AB  - An illustrated identification key is provided to 100 genera of Phlaeothripinae
      from China and Southeast Asia, together with a diagnosis for each genus, and
      comments on the species diversity. One new genus with a new species, Akarethrips
      iotus gen.n. & sp.n., and two new species, Heliothripoides boltoni sp.n. and
      Terthrothrips strasseni sp.n., are described from specimens collected in
      Peninsular Malaysia and Java respectively. Three Phlaeothripinae genera are
      synonymised, Mychiothrips Haga & Okajima syn.n. of Veerabahuthrips Ramakrishna,
      Syringothrips Priesner syn.n. of GigantothripsZimmermann, and Sauridothrips
      Priesner syn.n. of Gynaikothrips Zimmermann. In addition, four nomenclatural
      changes are included, Adelphothrips ignotus (Reyes) comb.n. transferred from
      Mesothrips, Karnyothrips palmerae (Chen) comb.n from Xylaplothrips, Xylaplothrips
      bogoriensis (Karny) comb.n from Brachythrips, and Oidanothrips notabilisFeng, Guo
      & Duan considered as a new synonym of Oidanothrips frontalis (Bagnall). 

PMID- 24871155
TI  - Two new species of Zwicknia Muranyi, with molecular data on the phylogenetic
      position of the genus (Plecoptera, Capniidae).
AB  - Analyses of the nuclear DNA marker 28S confirm the distinctness of the recently
      erected stonefly genus Zwicknia Muranyi 2014, which encompasses the species until
      recently referred to as 'Capnia bifrons.' Two new species are described and
      illustrated with line drawings: Z. westermanni Boumans & Muranyi, sp. n. from
      Germany and France, and Z. komica Muranyi & Boumans, sp. n. from the Komi
      Republic in northwestern Russia. The intersexual communication of the former
      species is described in detail. A phylogenetic analysis of 87 sequences of the
      mitochondrial marker cytochrome c oxidase I (COI) representing the six described
      European species of Zwicknia and outgroup taxa reveals large genetic distances
      within the species Z. rupprechti and Z. bifrons, while the haploclade including
      all specimens of the latter species also includes Z. acuta and Z. westermanni.
      The mitochondrial phylogeny is assumed not to represent the species phylogeny. In
      contrast, a phylogeny of the nuclear markers 28S and ITS reveals that Z.
      rupprechti and Z. westermanni are more closely related to each other than either
      is to Z. bifrons. This finding is in line with the drumming patterns of the
      former two species being relatively similar. 

PMID- 24871156
TI  - Illustrated catalogue and type designations of the New Zealand Zopheridae
      (Coleoptera: Tenebrionoidea).
AB  - This paper provides a comprehensive catalogue of the New Zealand members of the
      family Zopheridae Solier (Coleoptera: Tenebrionoidea) in an effort to stabilize
      the nomenclature preceding extensive revisionary taxonomy within the group. A
      checklist of the 17 New Zealand zopherid genera and an account for each of the
      189 species (by current combination) is provided. Type material for nearly all
      species was examined, and type specimens are designated herein (90 confirmed
      holotypes, 3 confirmed paratypes, 102 lectotypes, 280 paralectotypes). Images of
      all primary type specimens and labels examined are provided. Pycnomerus
      sulcatissimus Sharp, 1886 is a junior synonym and secondary homonym of Pycnomerus
      sulcatissimus (Reitter, 1880). One replacement name is proposed, Chorasus
      buckleyi new name, for Chorasus subcaecus (Broun), and 23 new combinations are
      given. 

PMID- 24871157
TI  - A revision of the Neotropical species of Lucilia Robineau-Desvoidy (Diptera:
      Calliphoridae).
AB  - A key to 23 species of Neotropical Lucilia, including six new species is given.
      Information is provided on all known Lucilia species found in the region,
      including the West Indies, Galapagos Islands, and Central and South America. The
      following six new species are described based on the examination of over 2700
      adult specimens from Central and South America: Lucilia albofusca sp. nov. from
      southern Central America and northern South America, Lucilia nitida sp. nov. from
      Brazil, Peru and Venezuela, Lucilia pulverulenta sp. nov. from Central America
      (Honduras south to Panama) and South America (Colombia and Ecuador), Lucilia
      rognesi sp. nov. from Costa Rica, Honduras and Panama, Lucilia vulgata sp. nov.
      from South America (widespread from Venezuela to Argentina), and Lucilia woodi
      sp. nov. from Central America (Honduras south to Panama). The status of Phaenicia
      japuhybensis Mello, 1961 is clarified; it is considered a valid species of
      Lucilia. Musca ochricornis Wiedemann, 1830 is removed from its current synonymy
      with Musca eximia Wiedemann, 1819 and considered a valid species of Lucilia.
      Lucilia mera Shannon & Del Ponte, 1926 and L. primaveris Shannon & Del Ponte,
      1926 are synonymized with L. ochricornis, syn. nov. Lucilia littoralis Blanchard
      1938 is synonymized with L. eximia (Wiedemann, 1819), syn. nov. Lectotypes are
      designated for L. mera, L. primaveris, and L. ochricornis. 

PMID- 24871159
TI  - Clinimetric properties of WOMAC Index in Greek knee osteoarthritis patients:
      comparisons with both self-reported and physical performance measures.
AB  - This observational study aimed to examine the clinimetric properties of the Greek
      for Greece translation of the Western Ontario and McMaster Osteoarthritis Index
      (WOMAC((r))). One hundred and twenty-three patients with knee osteoarthritis
      (mean age 69.5 years) participated in the study. An extensive reliability study
      was carried out to assess WOMAC's internal consistency and repeatability (8-day
      interval). In addition, we examined the construct (convergent, nomological and
      known-groups) and criterion-related (concurrent and predictive) validity of the
      index against both self-report [SF-36 and combined visual analog/faces pain scale
      revised (VAS/FPS-R)] and physical performance measures [timed up and go test
      (TUG)]. The internal consistency of the WOMAC subscales ranged from high (0.804)
      to excellent (0.956). Intra-class correlation coefficients for test-retest
      reliability were excellent, ranging from 0.91 to 0.95. Partial correlation
      analysis, adjusted for age and use of an assistive device, showed that WOMAC
      scores were significantly associated with all validation criteria, presenting
      fair to strong (-0.33 to -0.86) correlation coefficients. WOMAC-function was
      strongly associated with SF36-function (-0.86) and TUG (0.71), WOMAC-pain to
      VAS/FPS-R (0.71) and SF36-pain (-0.67). Of all WOMAC outcomes, stiffness subscale
      had the lowest, though still significant, correlations with all validation
      criteria. Multiple linear regression analyses indicated that WOMAC-function was a
      significant factor for TUG, WOMAC-pain for VAS/FPS-R and both for SF36-function
      and SF36-pain. The WOMAC LK3.1 Greek for Greece Index is a reliable and valid
      assessment tool for the evaluation of individuals with knee osteoarthritis,
      showing excellent reliability and significant validity properties.

PMID- 24871158
TI  - Impact of morning stiffness on working behaviour and performance in people with
      rheumatoid arthritis.
AB  - Work disability remains a considerable problem for many patients with rheumatoid
      arthritis (RA). Morning stiffness is a symptom of RA associated with early
      retirement from work and with impaired functional ability. We aimed to explore
      the patient's perception of the impact of morning stiffness on the working life
      of patients with RA. A survey was conducted in 11 European countries. Patients of
      working age, with RA for >=6 months and morning stiffness >=3 mornings a week,
      were interviewed by telephone using a structured questionnaire. Responses were
      assessed in the total sample and in subgroups defined by severity and duration of
      morning stiffness and by country. A total of 1,061 respondents completed the
      survey, 534 were working, 224 were retired and the rest were, i.e. homemakers and
      unemployed. Among the 534 working respondents, RA-related morning stiffness
      affected work performance (47 %), resulted in late arrival at work (33 %) and
      required sick leave in the past month (15 %). Of the 224 retired respondents, 159
      (71 %) stopped working earlier than their expected retirement age, with 64 %
      giving RA-related morning stiffness as a reason. There was a differential impact
      of increasing severity and increasing duration of morning stiffness on the
      various parameters studied. There were notable inter-country differences in the
      impact of RA-related morning stiffness on ability to work and on retirement. This
      large survey showed that from the patient's perspective, morning stiffness
      reduces the ability to work in patients with RA and contributes to early
      retirement.

PMID- 24871160
TI  - Survival analysis and risk factors for mortality in connective tissue disease
      associated pneumomediastinum.
AB  - The aim of this study was to analyze the characteristics of patients with diffuse
      connective tissue diseases (CTDs) complicated by pneumomediastinum and identify
      the risk factors associated with increased mortality in these patients. Twenty
      eight patients with CTD-associated pneumomediastinum, who were admitted to our
      hospital from January 1997 to June 2012, were prospectively studied. Their
      demographic characteristics, time to death, and potential risk factors were
      assessed. Survival curves were depicted by the Kaplan-Meier method. Univariate
      and multivariate survival analyses were performed by Cox regression. Of the 28
      patients, 21 had dermatomyositis; two, polymyositis; three, systemic lupus
      erythematosus; one, polyarteritis nodosa; and one, undifferentiated CTD. The mean
      follow-up period was 1,461 days (54-5,264). The cumulative estimated Kaplan-Meier
      survival rate was 68 % at 1 week, 50 % at 1 month, and 43 % at 1 year. According
      to univariate analysis, higher serum albumin level (HR 0.87, 95 % CI 0.78-0.98),
      "slow air leak" (defined as time to progression of dyspnea [newly acquired
      respiratory failure, mechanical ventilation required, or decrease in PaO2 >30
      mmHg after pneumomediastinum]) >3 days (HR 0.07, 95 % CI 0.02-0.34), and early
      initiation of immunosuppressive agents (within 1 month of steroid therapy; HR
      0.27, 95 % CI 0.09-0.81) were associated with better prognosis. Final regression
      analysis revealed that slow air leak was associated with a lower mortality risk.
      We found that slow air leak was independently associated with better prognosis.
      Furthermore, most patients (86 %) who survived for at least 1 month following the
      pneumomediastinum event subsequently survived beyond 1 year.

PMID- 24871162
TI  - One-pot synthesis of vinca alkaloids-phomopsin hybrids.
AB  - Hybrids of vinca alkaloids and phomopsin A have been elaborated with the aim of
      interfering with the "vinca site" and the "peptide site" of the vinca domain in
      tubulin. They were synthesized by an efficient one-pot procedure that directly
      links the octahydrophomopsin lateral chain to the velbenamine moiety of 7'-homo
      anhydrovinblastine. In their modeled complexes with tubulin, these hybrids were
      found to superimpose nicely on the tubulin-bound structures of vinblastine and
      phomopsin A. This good matching can account for the fact that two of them are
      very potent inhibitors of microtubules assembly and are cytotoxic against four
      cancer cell lines. 

PMID- 24871161
TI  - Sociocultural factors influencing HIV disclosure among men in South Africa.
AB  - In South Africa, more than 2 million people living with HIV are men aged 15 years
      and older, and heterosexual intercourse remains the predominant mode of HIV
      transmission. Knowledge of the sociocultural factors that influence men's
      decisions about whether, when, or how to disclose seropositive status remains
      incompletely understood. Using the PEN-3 cultural model as a guide, this study
      explored the sociocultural factors influencing HIV disclosure among men in South
      Africa. Four focus group discussions with 27 participants were used to determine
      the perceptions, enabling and nurturing factors that influence how men chose to
      reveal or conceal knowledge of their seropositive status. The results revealed
      that notions of male identity in the South African context, family, and community
      factors contribute to disclosure and nondisclosure of seropositive status among
      men living with HIV/AIDS. Future interventions should work to address these
      factors, as they are necessary with supporting disclosure among men living with
      HIV.

PMID- 24871163
TI  - Zebragryllus Desutter-Grandcolas & Cadena-Castenada, n.gen. a new Gryllinae genus
      from Eastern and Western Amazonia, South America (Orthoptera, Grylloidea,
      Gryllidae).
AB  - We describe a new genus of grylline cricket, Zebragryllus Desutter-Grandcolas &
      Cadena-Castenada n. gen., from the Neotropical Region, using characters of
      morphology and male genitalia; genitalic characters clearly show that
      Zebragryllus n. gen. is closely related to Anurogryllus Saussure, 1878. Six
      species are described as new to science, origina<a
      href="http://dx.doi.org/10.1046/j.1463-6409.2003.00142.x">t</a>ing from western
      (Peru, Colombia) and eastern (French Guiana) Amazonia: Zebragryllus fuscus
      Desutter-Grandcolas, n. sp., Z. guianensis Desutter-Grandcolas, n. sp., Z.
      intermedius Desutter-Grandcolas, n. sp., Zebragryllus nauta Desutter-Grandcolas,
      n. sp., Zebragryllus nouragui Desutter-Grandcolas, n. sp., and Zebragryllus
      wittoto Desutter-Grandcolas and Cadena-Castenada, n. sp., type species of the
      genus. They are characterized by their size, coloration (shining black, most
      often with white patterns of coloration, hence the genus name), and male and
      female genitalia. The calling songs of Z. guianensis Desutter-Grandcolas, n. sp.,
      Z. intermedius Desutter-Grandcolas, n. sp., Z. nouragui Desutter-Grandcolas, n.
      sp., and Z. wittoto Desutter-Grandcolas and Cadena-Castenada, n. sp. are
      described. An identification key is proposed for both males and females. 

PMID- 24871164
TI  - Revision of the subgenus Parapterygotrigla (Pisces: Triglidae: Pterygotrigla) .
AB  - The subgenus Parapterygotrigla of the triglid genus Pterygotrigla is revised with
      a description of a new species. The subgenus comprises P. hoplites, P. jacad sp.
      nov., P. megalops, P. macrorhynchus, P. multiocellata, and P. robertsi. Two
      juvenile forms considered to be incertae sedis Dixiphichthys ferculum Whitley,
      and two larval triglids, are discussed together with Trigla brandesii (Bleeker).
      Members of the subgenus Parapterygotrigla are distributed in tropical waters of
      the western Pacific and Indian oceans. All species possess a nasal spine, have
      long and strong nuchal and cleithral spines and short opercular spines. A new
      species, P. jacad, found in the western Indian Ocean, has an unusually large eye.
      All members of the subgenus are rare in collections as they live on the bottom in
      deep water (>200 m) over rough terrain and are rarely taken by trawlers. 

PMID- 24871165
TI  - Two new species of Digamasellidae from Taiwan (Acari: Mesostigmata).
AB  - This paper reports the occurrence of two new species of Digamasellidae from
      Taiwan, Dendroseius vulgaris n. sp. and Dendrolaelaps (Foveodendrolaelaps)
      linjianzheni n. sp. Dendroseius vulgaris is described based on the morphology of
      adult females, adult males and deutonymph, and D. linjianzheni is based on the
      morphology of adult females and males. This is the first report on the mite
      species of Digamasellidae from Taiwan.  

PMID- 24871166
TI  - Two new species of Phareicranaus Roewer, 1913 (Opiliones: Laniatores: Cranaidae),
      with notes on gregarious behavior and maternal care in Phareicranaus manauara.
AB  - In this paper we describe two new species of Phareicranaus Roewer, 1913:
      Phareicranaus rohei sp. nov. from the state of Amazonas, Brazil and Phareicranaus
      tizana sp. nov., from the state of Zulia, Venezuela. The number of known species
      of this genus increases to 47. We discuss and suggest the possible relationships
      of these species with their relatives and assign them into the clades proposed by
      Pinto-da-Rocha & Bonaldo (2011). Additionally, we conducted field observations at
      the type locality of Phareicranaus manauara (Pinto-da-Rocha, 1994), provide the
      first descriptions of maternal care and gregarious behavior, and discuss the
      occurrence of this behavior in the genus. 

PMID- 24871167
TI  - New digeneans (Opecoelidae) from hydrothermal vent fishes in the south eastern
      Pacific Ocean, including one new genus and five new species.
AB  - A new genus and five new species of digeneans are reported from fishes at
      hydrothermal vent sites in the South East Pacific Rise region. Biospeedotrema n.
      gen. (Opecoelidae: Stenakrinae) is distinguished from other stenakrines by the
      more or less symmetrical testicular configuration, with the uterus passing
      between the testes, sometimes distinctly into the post-testicular region.
      Biospeedotrema jolliveti n. gen., n. sp. from Ventichthys biospeedoi (Ophidiidae)
      is distinguished by the vitelline fields which extend only slightly into the post
      testicular region, the intestinal bifurcation is dorsal to the ventral sucker,
      the genital pore is slightly dextrally submedian or median, the cirrus sac is
      short and the caeca are broad and overlap the testes, usually reaching into the
      post-testicular region. Biospeedotrema parajolliveti n. sp. from Thermichthys
      hollisi differs from Biospeedotrema jolliveti in being squat, always just wider
      than long, the tegument is wrinkled, the testes are lobate, and the caeca only
      just reach to the testes. Biospeedotrema biospeedoi n. sp. from T. hollisi
      differs from its congeners in its body-shape, uterine extent posterior to the
      testes and the small vitellarium. Caudotestis ventichthysi n. sp. (Opecoelidae:
      Stenakrinae) from V. biospeedoi is distinguished from its five congeners in
      various combinations of caecal length, cirrus sac length, internal seminal
      vesicle shape, vitelline extent and distribution, forebody length and egg-size.
      Buticulotrema thermichthysi n. sp. (Opecoelidae: Opecoelininae) from T. hollisi
      (Bythitidae) is distinguished from its only congener by its very long, very
      strongly muscular oesophagus, bifurcating dorsally to the posterior part of the
      ventral sucker, the long, narrow pars prostatica and distal male duct and the
      sinistral genital pore at the level of the pharynx. The phylogenetic position for
      three of these species, Buticulotrema thermichthysi, Biospeedotrema jolliveti and
      Biospeedotrema biospeedoi, is assessed based on ssrDNA and lsrDNA sequences,
      which verify the position of these species in the Opecoelidae.  

PMID- 24871169
TI  - Descriptions of two new species of Myrmedonota Cameron (Staphylinidae:
      Aleocharinae) from Mexico with comments on the genus taxonomy and behavior.
AB  - Two new species of Myrmedonota, M. shimmerale n. sp. and M. xipe n. sp., are
      described, and the genus is recorded from Mexico for the first time. Dorsal
      habitus photographs, illustrations of the median lobe and spermatheca are
      presented for diagnostic purposes. We suggest that Myrmedonota is in fact diverse
      in the New World and that its taxonomy is already in a state of confusion. New
      behavioral observations show that: (1) Myrmedonota species will aggregate towards
      agitated ants, possibly to prey on them; (2) Myrmedonota will form mating swarms,
      either with no apparent landmark or in the vicinity of ants. 

PMID- 24871168
TI  - A new species of the alpheid shrimp genus Triacanthoneus Anker, 2010 (Crustacea:
      Alpheidae) from Belize.
AB  - A new species of the alpheid shrimp genus Triacanthoneus Anker, 2010, is
      described based on material collected in a marine cave off Caye Chapel, Belize.
      Triacanthoneus chapelianus sp. nov. is the fifth species in the genus and can be
      distinguished from the other four species by the position of the dorsolateral
      teeth on the carapace, which in the new species have an anterior (= submarginal)
      position, and by the configuration of the posterior margin of the telson, with a
      notch in the middle portion and two pairs of spines and one pair of plumose
      setae. A key to the five species of Triacanthoneus is provided. 

PMID- 24871170
TI  - Comparative descriptions of non-adult stages of four genera of Gordiids (Phylum:
      Nematomorpha).
AB  - Freshwater hairworms infect terrestrial arthropods as larvae but are free-living
      in aquatic habitats as adults. Estimates suggest that only 18% of hairworm
      species have been described globally and biodiversity studies on this group have
      been hindered by unreliable ways of collecting adult free living worms over large
      geographical areas. However, recent work indicates that non-adult cyst stages of
      hairworms may be the most commonly encountered stages of gordiids in the
      environment, and can be used for discovering the hidden diversity of this group.
      Unfortunately, little information is available on the morphological
      characteristics of non-adult stages of hairworms. To address this problem, we
      describe and compare morphological characteristics of non-adult stages for nine
      species of African and North American gordiids from four genera (Chordodes,
      Gordius, Paragordius, and Neochordodes). Observations were made on the
      oviposition behavior of adult worms and morphological characteristics were
      recorded for egg strings, larvae and cysts using light and differential
      interference contrast microscopy and/or scanning electron microscopy. Our study
      indicates that three distinct types of oviposition behaviors and three distinct
      morphological types of egg string, larva, and cysts were present among the four
      genera of gordiids. Although species identification based on cyst characteristics
      was not always possible among different species of gordiids, cyst morphology was
      conserved among some genera and all clades of gordiids. More importantly, our
      work indicates that gordiid larval morphology can be used for predicting cyst
      morphology among other gordiid genera. The capability to identify and predict
      gordiid genera and/or clades based on cyst morphology will be useful for
      culturing gordiids in the laboratory from field collected cysts and these new
      techniques will undoubtedly allow others to discover new species of gordiids from
      around the world. 

PMID- 24871171
TI  - Six new species of the spider family Ochyroceratidae Fage 1912 (Arachnida:
      Araneae) from Southeast Asia.
AB  - Five new Althepus species and one new Psiloderces species of the family
      Ochyroceratidae are described from Southeast Asia: Althepus erectus spec. nov.
      (male) and A. nophaseudi spec. nov. (male, female) from Laos, A. flabellaris
      spec. nov. (male, female) from Thailand, A. reduncus spec. nov. (male) from
      Myanmar, A. spiralis spec. nov. (male) from Malaysia, and Psiloderces
      dicellocerus spec. nov. (male) from Indonesia. Primary types are deposited in the
      Senckenberg Research Institute in Frankfurt, Germany (SMF). 

PMID- 24871172
TI  - Molecular and morphological assessment of Varanus pilbarensis (Squamata:
      Varanidae), with a description of a new species from the southern Pilbara,
      Western Australia.
AB  - Varanus pilbarensis Storr, 1980 is a specialised saxicolous varanid endemic to
      the Pilbara region of Western Australia. We present genetic and morphological
      evidence confirming the existence of a divergent southern lineage, here described
      as V. hamersleyensis sp. nov.. The new species differs noticeably in having a
      darker colouration and a reduced pattern of small whitish ocelli on the dorsal
      surface of the limbs only with a largely unbanded tail. By contrast, V.
      pilbarensis which is redescribed and restricted to the northern lineage, is paler
      and more boldly patterned with large greyish ocelli on the dorsal and lateral
      surfaces of the body and a strongly banded tail. The two species have discrete
      distributions centred on the Chichester and Hamersley Ranges to the north and
      south of the Fortescue River Basin. This pattern of intraregional genetic
      structuring is similar to that found in a number of other saxicolous lizard
      lineages from the Pilbara. 

PMID- 24871173
TI  - Cryptic species diversity in marsupial frogs (Anura: Hemiphractidae: Gastrotheca)
      in the Andes of northern Peru.
AB  - Molecular phylogenetic analysis revealed the existence of two undescribed species
      of the hemiphractid genus Gastrotheca in the Andes in northern Peru. Both species
      are similar morphologically to Gastrotheca dysprosita and G. monticola, but they
      differ from these species and from one another in subtleties of coloration and
      minor variances in size and proportions. Gastrotheca aguaruna sp. nov. (610'50"S,
      7737'01"W, 2480 m) is from humid forested areas in the northern part of the
      Cordillera Central, whereas G. aratia sp. nov. (614'00"S, 7851'24"W, 2560 m ) is
      known from the northern part of the Cordillera Occidental.

PMID- 24871174
TI  - New taxa of the family Syringophilidae (Acari: Prostigmata) from African barbets
      and woodpeckers (Piciformes: Lybiidae, Picidae).
AB  - New taxa of quill mites (Acari: Syringophilidae) are described from African
      barbets and woodpeckers in the Ethiopian region. A new monotypic genus
      Picineoaulonastus gen. nov. is established for a new species Picineoaulonastus
      pogoniulus sp. nov., parasitising 2 lybiid species, Pogoniulus bilineatus
      (Sundevall) (type host) in Kenya and Tanzania and P. pusillus (Dumont)
      (Piciformes: Lybiidae) in Ethiopia. Additionally, 2 more new syringophilid
      species are described: Neosyringophilopsis lybidus sp. nov. from P. bilineatus in
      Kenya, and Syringophiloidus picidus sp. nov. from Dendropicos fuscescens
      (Vieillot) (Piciformes: Picidae) in Kenya, Uganda, and Tanzania. 

PMID- 24871175
TI  - A new species of the genus Ishikawatrechus (Coleoptera, Trechinae) from Japan.
AB  - A new species, Ishikawatrechus bidilatatus sp. nov., is described from the
      northwestern part of the Ishizuchi Range, Shikoku, Japan. The structure of the
      everted internal sac of the aedeagus in a fully inflated condition is observed
      and the taxonomic significance is discussed by comparing with a related species,
      I. ishiharai Ueno, 1994. 

PMID- 24871176
TI  - A new species of the genus Anthaxia Eschscholtz, 1829 from Spain (Coleoptera:
      Buprestidae: Buprestinae: Anthaxiini).
AB  - Anthaxia (Anthaxia) madridensis, sp. nov. from central Spain is described,
      illustrated and compared with the most similar species. The bionomy and the
      history of the discovery of the new species is briefly discussed. 

PMID- 24871177
TI  - Twenty seven new species of Orthocentrus (Hymenoptera: Ichneumonidae;
      Orthocentrinae) with a key to the Neotropical species of the genus.
AB  - We describe 27 new species of parasitoid wasps of the genus Orthocentrus
      (Ichneumonidae: Orthocentrinae) from the Neotropical region, where previously
      only one species of the genus (O. insularis Ashmead) was known, and provide a key
      to all described Orthocentrus species of the region. Based on previous studies
      and additional material that we have seen from the region, describing these
      species is only an initial attempt to document the Neotropical orthocentrine
      fauna. 

PMID- 24871178
TI  - One or two species? On the case of Hyperolius discodactylus Ahl, 1931 and H.
      alticola Ahl, 1931 (Anura: Hyperoliidae).
AB  - In 1931, Ernst Ahl described two species of reed frogs inhabiting montane forests
      of the Albertine Rift in East Africa, Hyperolius alticola and H. discodactylus,
      which were synonymized two decades later by Raymond Laurent. Since then, this
      revision has been questioned repeatedly, but taxonomists have been reluctant to
      make a conclusive decision on the matter, especially since the type material of
      H. alticola was reported as being lost. Here, we examine the rediscovered type
      material of H. alticola and reassess the validity of Laurent's synonymy using
      morphological data from historic and new collections including all available type
      material, call recordings and molecular data from animals collected on recent
      expeditions. We find evidence for a northern and southern genetic clade, a divide
      that is somewhat supported by diverging morphology as well. However, no
      distinction in advertisement calls could be recovered to support this split and
      both genetic and morphological differences between geographic units are marginal
      and not always congruent and thus more likely reflect population-level variation.
      We therefore conclude that H. alticola is not a valid taxon and should continue
      to be treated as a synonym of H. discodactylus. Finally, we also report on newly
      collected material from outside the species known range, with first records of
      this species from Burundi. 

PMID- 24871179
TI  - Faunistic survey of Hydromedusae (Cnidaria, Medusozoa) from the coast of Parana
      State, Southern Brazil.
AB  - This study is the first faunistic inventory of hydromedusae from the inner
      continental shelf of Parana State. We describe the composition of hydromedusae
      species, collected with bottom-trawl and Hensen nets, in campaigns carried out
      from 1997 to 2006. We analyzed 17,797 specimens from 578 samples, and provide
      descriptions, photographs, and information about the biology of the 22 species
      found. All species had previous records from the Brazilian coast; however, this
      is the first record of Bougainvillia frondosa, Ectopleura dumortieri,
      Cirrholovenia tetranema, Eucheilota maculata, Gossea brachymera, Solmaris corona,
      and Amphogona apsteini for the coast of Parana. Most species are typical of
      tropical and subtropical coastal waters from the South Brazilian Bight. However,
      Turritopsis nutricula, Niobia dendrotentaculata, Solmaris corona, and Aglaura
      hemistoma are abundant in oceanic waters, and Olindias sambaquiensis and Solmaris
      corona are associated with colder waters (<20 degrees C). The current number of
      species known for the state is 26. Additional collection effort is needed in
      regions not sampled in this work, such as bays and offshore waters. 

PMID- 24871180
TI  - New species and records of Asymmetrasca (Hemiptera: Cicadellidae: Typhlocybinae:
      Empoascini) from China and name changes in Empoasca (Matsumurasca).
AB  - Six new species of Asymmetrasca Dlabola are described from China: A.
      dahaituoensis, A. helica, A. hypercurvata, A. liaoensis, A. reflexilis, A. uncus
      spp. nov. In addition, A. cienka Dworakowska, 1982, n. comb.; A. decedens Paoli,
      1932 and A. sakaii Dworakowska 1971, n. comb., are recorded from China for the
      first time. The following additional new combinations from Empoasca are also
      proposed: A. cisiana (Dworakowska, 1971); A. kaicola (Dworakowska, 1982), A.
      lutowa (Dworakowska, 1971), A. mona (Dworakowska, 1994), A. nipponica
      (Dworakowska 1982), A. rybiogon (Dworakowska, 1971), and A. uniprossicae (Sohi,
      1977). Empoasca (Empoasca) kishtwarensis Sharma, 1984 is proposed as a new
      synonym of Asymmetrasca kaicola (Dworakowska, 1982). Habitus photos and
      illustrations of the male genitalia of the new species and a key to Chinese
      species are provided. New names are proposed to replace two junior homonyms in
      Empoasca (Matsumurasca). 

PMID- 24871181
TI  - External egg structure of the Pentatomidae (Hemiptera: Heteroptera) and the
      search for characters with phylogenetic importance.
AB  - The chorionic structure of sixteen pentatomid species is described. Morphological
      patterns in different taxonomic levels are discussed. In addition, egg characters
      useful in cladistic analyses are listed, and some of those characters are tested
      for congruence with two cladistic analyses previously conducted within
      Pentatomidae. Descriptive studies were conducted with Banasa induta, Capivaccius
      bufo, Catulona pensa, Chinavia armigera, Chinavia aseada, Chinavia brasicola,
      Chinavia runaspis, Dichelops furcatus, Euschistus heros, Euschistus
      riograndensis, Euschistus paranticus, Mormidea cornicollis, Podisus distinctus,
      Podisus nigrispinus, Serdia apicicornis, and Thoreyella maracaja. The eggs were
      examined and photographed under light and scanning electron microscopy. Based on
      literature data, a list of 40 egg characters with potential phylogenetic
      importance has been compiled. Some of these characters were included in the
      cladistic analyses of the genus Nezara (six characters) and of the Chinavia
      obstinata group (five characters). Both analyses were performed in TNT with equal
      weighting of characters. The eggs of most of the Neotropical species studied were
      barrel-shaped, chorion translucent and spinose, with aero-micropylar processes
      that were short and clubbed. The patterns of egg morphology could be identified
      in Carpocorini, Procleticini, and in the genera Banasa, Chinavia, Euschistus,
      Mormidea, and Podisus. In the cladistic analyses, the inclusion of egg characters
      did not affect the topology of the trees shown in the original papers. For the
      analyses, the egg characters were somewhat informative. At present, a total of
      286 Pentatomidae species have their egg stage described.  

PMID- 24871182
TI  - A new species of the subterranean amphipod genus Stygobromus (Amphipoda:
      Crangonyctidae) from two caves and a spring in western Maryland, USA with
      additional records of undescribed species from groundwater habitats in central
      Maryland.
AB  - A new species of the subterranean amphipod genus Stygobromus is described from
      two caves and a small spring on the Appalachian Plateau in Garrett County in
      western Maryland, USA. The description of this species brings to six the total
      number of species in the genus Stygobromus from the state of Maryland. The other
      five species are recorded from shallow groundwater habitats (e.g., seeps and
      springs) in the eastern and southeastern parts of the state. In addition, at
      least four new species of Stygobromus from central Maryland are recognized but
      remain undescribed to date. 

PMID- 24871183
TI  - Aradidae from Vietnam III. Trichosomaptera gibbosa n.gen., n.sp., an apterous
      Carventinae (Hemiptera: Heteroptera: Aradidae) .
AB  - A new apterous flat bug genus of the subfamily Carventinae, Trichosomaptera
      n.gen., is described and illustrated to accommodate gibbosa n. sp. from Vietnam.
      The species could not be placed in any known genus. 

PMID- 24871184
TI  - Revision of the Culicoides (Avaritia) Imicola complex Khamala & Kettle (Diptera:
      Ceratopogonidae) from the Australasian region.
AB  - The monophyly of the Imicola complex, a natural species complex within subgenus
      C. subgen. Avaritia Fox of the biting midge genus Culicoides Latreille, is
      supported using morphological and molecular analyses. A diagnosis for the group
      along with comparative redescriptions of the male and female of the species
      represented in Australasia, C. brevitarsis Kieffer and C. nudipalpis Delfinado
      and a description of C. asiatica Bellis sp. nov., are presented together with
      keys for their specific determination and molecular support for their status. 

PMID- 24871185
TI  - Morphology of the first zoeal stage of three deep-water pandalid shrimps,
      Heterocarpus abulbus Yang, Chan & Chu, 2010, H. hayashii Crosnier, 1988 and H.
      sibogae De Man, 1917 (Crustacea: Decapoda: Caridea).
AB  - The eggs of three deep-sea pandalid shrimps Heterocarpus abulbus, H. hayashii and
      H. sibogae are successfully hatched in the laboratory. The first zoeal stage of
      these shrimps are described, with those of H. abulbus and H. hayashii being
      reported for the first time. First zoeae of different Heterocarpus species can be
      distinguished by the spination at the anteroventral carapace, body size, rostral
      length and appendage setation.  

PMID- 24871186
TI  - The old-world Zygonini tr. nov. (Hemiptera, Cercopoidea, Clastopteridae), with
      new taxa from the related Machaerotinae.
AB  - Three new species of old-world Clastopteridae belonging to Machaerotinae are
      described, two in new monobasic genera: Allox transfigurata (Hindolini) from
      Borneo and Irridiculum deformatum (Machaerotini) from Sulawesi. One new species
      Machaeropsis dramatica (Hindolini) is described from Borneo. It is the first male
      known from the genus and shows that Machaeropsis Melichar is not synonymous with
      Metaenderleinia Lallemand. Five other new species are described, belonging to a
      new, related tribe Zygonini. Two of these new species (Ambonga lanceolata and
      Pseudomachaerota cucullata) belong to formerly monobasic genera from Madagascar
      incorrectly assigned to Cercopidae and Aphrophoridae respectively. These are
      related to 3 new genera: (1) from Madagascar, Pseudoclastoptera with new species
      P. irrubesco and P. invidia; from sub-Saharan Africa, (2) Zygon with 1 new
      species Z. desegregatum, and (3) Hemizygon, the latter with 2 new combinations
      from Pseudomachaerota: H. grande (Maa) and H. saturnus (Linnavuori). Zygon is
      possibly the most basal genus in Clastopteridae, according to its remarkable
      antennal characters with 5 different types of sensilla that show how basiconic
      and coeloconic sensilla are homodynamous. Genera related to Zygon are widely
      divergent from other spittlebugs as measured by mDNA "barcode" data from the COI
      gene. 

PMID- 24871187
TI  - The geometrid moths of Ethiopia I: tribes Pseudoterpnini and Comibaenini
      (Lepidoptera: Geometridae, Geometrinae).
AB  - In this paper we present a checklist for Ethiopian Geometridae, subfamily
      Geometrinae, tribes Pseudoterpnini and Comibaenini. Six species were found to
      belong to the tribe Pseudoterpnini, two species to the tribe Comibaenini. One
      species is described as new, Comibaena theodori sp. nov. Adults of all species
      are illustrated, genitalia are figured for the new species. 

PMID- 24871188
TI  - Revision of the Hylaea fasciaria (Linnaeus, 1758) species group in the western
      Palaearctic (Lepidoptera: Geometridae, Ennominae).
AB  - The Palaearctic Hylaea fasciaria (Linnaeus, 1758) species group is revised
      (Lepidoptera: Geometridae, Ennominae). Four taxa are considered valid at species
      level: H. fasciaria (Linnaeus, 1758), H. pinicolaria (Bellier, 1861), H.
      compararia (Staudinger, 1894) and one new species, H. mediterranea, from Italy:
      Sicily, Calabria and Molise. The following taxonomic changes are proposed:
      Ellopia cedricola Wehrli, 1919, from Turkey is downgraded to subspecies of Hylaea
      fasciaria (Linnaeus, 1758) (revised status), Hylaea fasciaria cleui Leraut, 1993,
      from France is downgraded from subspecies to synonymy with H. fasciaria fasciaria
      (Linnaeus, 1758) (new synonymy) and Ellopia compararia Staudinger, 1894, from
      Algeria is raised from subspecies of Hylaea fasciaria (Linnaeus, 1758) to species
      status (revised status). Hemithea squalidaria O. G. Costa, 1848 from southern
      Italy was placed in the genus Hylaea, but it is reverted to its original
      combination as its taxonomic status is uncertain. Adults, male and female
      genitalia and distribution maps are illustrated for all species. DNA barcodes are
      presented for most taxa studied. 

PMID- 24871189
TI  - The first discovery of the genus Meira Jacquelin du Val outside the western
      mediterranean area, with description of a new species (Coleoptera, Curculionidae,
      Entiminae).
AB  - A new species of Meira Jacquelin du Val, 1852 from northeast Italy is described:
      Meira mariaesilvanae sp. n. This is the first discovery of the genus Meira in the
      northeast of Italy outside the hitherto known distribution. Ecological and
      distributional data are provided for the new species. Photos of habitus, some
      morphological details, genitalia and of the type locality illustrate the work. 
      In addition we provide a dichotomous key to Italian species and a checklist to
      known Meira species. 

PMID- 24871190
TI  - Overestimation of molecular and modelling methods and underestimation of
      traditional taxonomy leads to real problems in assessing and handling of the
      world's biodiversity.
AB  - Since the 1992 Rio Convention on Biological Diversity, the earth's biodiversity
      is a matter of constant public interest, but the community of scientists who
      describe and delimit species in mega-diverse animal groups, i.e. the bulk of
      global biodiversity, faces ever-increasing impediments. The problems are rooted
      in poor understanding of specificity of taxonomy, and overestimation of
      quantitative approaches and modern technology. A high proportion of the animal
      species still remains to be discovered and studied, so a more balanced approach
      to the situation is needed. 

PMID- 24871191
TI  - The Tryphosa group (Crustacea: Amphipoda: Lysianassoidea: Lysianassidae:
      Tryphosinae).
AB  - The Tryphosa group is established within the tryphosine amphipods. It contains
      eight genera worldwide (Bruunosa Barnard & Karaman, 1987; Glorieusella gen. nov.;
      Gronella Barnard & Karaman, 1991; Metambasia Stephensen, 1923; Pseudonesimus
      Chevreux, 1926; Schisturella Norman, 1900; Thrombasia J.L. Barnard, 1966; and
      Tryphosa Boeck, 1871). As part of the Tryphosa group we describe the new genus
      Glorieusella from Madagascar and four new species (Schisturella rosa sp. nov.,
      Thrombasia evalina sp. nov., Thrombasia umina sp. nov., Thrombasia saros sp.
      nov.) from eastern Australia. 

PMID- 24871192
TI  - Description, DNA barcode and phylogeny of a new species, Macrobrachium abrahami
      (Decapoda: Palaemonidae) from Kerala, India.
AB  - Macrobrachium abrahami, new species is described from Vamanapuram River, Kerala,
      South India. DNA bar-coding using Cytochrome B gene sequences has elucidated the
      taxonomic status of the new species and the ML tree reveals that M. abrahami sp.
      nov., is phylogenetically close to M. prabhakarani, but morphologically more
      similar to M. scabriculum. However, the species shares certain morphological
      characters with M. scabriculum, M. prabhakarani and M. lanatum, but differs
      remarkably from these three species in distinctive diagnostic characters: rostrum
      moderately long, convex, distal end directed upwards, rostral formula 12-15/2-3
      with 5-6 postorbital teeth, and carapace glabrous. In larger second chelate leg,
      fingers stout, pubescence restricted to their base; proximal half of cutting edge
      with fifteen denticles. In smaller second chelate leg, cutting edge of both
      fingers carry six small denticles situated proximally, distal one comparatively
      larger. Delicate setae are seen throughout the palm. A row of dark chromatophores
      is present along the posterio-dorsal margin of uropodal exopods and endopods,
      close to the base of uropodal setae. The thickness of each band of the row is
      almost equal to the thickness of uropodal setae. 

PMID- 24871193
TI  - New species of Monodontocerus (Collembola: Tomoceridae) from southern China with
      diagnostic notes on the genus and introduction of new taxonomic characters.
AB  - Three new species of Monodontocerus are described from caves in southern China:
      M. absens sp. nov. is characterized by its cephalic chaetotaxy and the absence of
      chaetae from the tenaculum; M. mulunensis sp. nov. is characterized by a
      combination of characters including chaetotaxy, foot complex and furca; M.
      trigrandis sp. nov. is different from other species in the formula of dental
      spines and the reduction of the ungual teeth. A key to the species of
      Monodontocerus is provided. Potential diagnostic characters for this genus are
      proposed. Troglomorphy and interspecific variability are discussed. Pseudopores
      and the dorsal disto-lateral chaeta on the manubrium are introduced as new
      taxonomic characters for Tomocerinae.  

PMID- 24871194
TI  - A new species of Malayopotamon Bott, 1968 (Crustacea: Decapoda: Brachyura:
      Potamidae), a freshwater crab from northern Sumatra, Indonesia.
AB  - A new species of potamid freshwater crab, Malayopotamon weh sp. nov., is
      described from the island of Pulau Weh off northern Sumatra, Indonesia. The
      species superficially resembles three Sumatran species: M. batak Ng & Wowor,
      1991, M. tobaense (Bott, 1968), and M. turgeo Ng & Tan, 1999, but can easily be
      distinguished by various carapace as well as gonopod characters. 

PMID- 24871195
TI  - A new cavefish species from Southwest China, Sinocyclocheilus gracilicaudatus sp.
      nov. (Teleostei: Cypriniformes: Cyprinidae).
AB  - One new species is added to the genus Sinocyclocheilus, the largest cyprinid
      genus in China and the largest cavefish genus in the world. Sinocyclocheilus
      gracilicaudatus sp. nov. is similar to S. donglanensis but differs to other
      congeners in having normal eyes and scaled body, curved lateral line with 59-64
      lateral-line scale rows, half-hard dorsal fin spine, 8 gill rakers and 8
      predorsal vertebrae. Compared to S. donglanensis, the new species has a longer
      and more narrow caudal peduncle (caudal peduncle length 21.3-22.7% vs. 16.8-20.4%
      of SL; caudal peduncle depth 10.5-12.0% vs. 12.5-15.5% of SL), smaller eyes (eye
      diameter 5.8-8.3% vs. 6.5-10.9% of SL) and longer barbels (maxillary barbel
      length 16.6-24.3% vs. 11.1-21.1 % of SL; rictal barbel length 19.5-21.6% vs. 11.3
      21.1% of SL). The new species is distributed in a subterranean river, belonging
      to the Longjiang River system; S. donglanensis occurs in the Hongshuihe River
      system, a system separate from that where the former species occurs.  

PMID- 24871196
TI  - The first ibis fly in mid-Cretaceous amber of France (Diptera: Athericidae).
AB  - A new genus and species of ibis fly is described from an isolated wing in amber
      from the Late Albian-Early Cenomanian of Charentes, southwestern France.
      Galloatherix incompletus gen. et sp. n., is the first Athericidae fossilized in
      Cretaceous amber, and only the eighth Mesozoic species. It adds to the diverse
      aquatic and semiaquatic paleobiota already identified from Charentese amber.  

PMID- 24871197
TI  - A new genus for a Chilean species of Acanthosomatidae (Hemiptera: Heteroptera).
AB  - Sinopla canaliculus Reed, 1898 is revalidated and illustrated for first time.
      Pseudosinopla n. gen. (Blaudusinae: Lanopini) is erected to place S. canaliculus
      Reed, 1898. A key to Chilean Lanopini genera is included. 

PMID- 24871198
TI  - Genetic localization of a TetR-like transcriptional regulator gene in Pseudomonas
      fluorescens isolated from farmed fish.
AB  - Pseudomonas fluorescens isolates from Tanzanian tilapia ponds were found to
      possess a gene encoding a TetR-like transcriptional regulator protein.
      Phylogenetic analysis revealed close similarity to five previously reported
      GeneBank sequences which cluster separately from the other 70 members of this
      family. It is assumed that this TetR-like protein belongs to a new family of TetR
      like proteins that has no direct link to the class 1 integron.

PMID- 24871199
TI  - Fatty acid composition and desaturase gene expression in flax (Linum
      usitatissimum L.).
AB  - Little is known about the relationship between expression levels of fatty acid
      desaturase genes during seed development and fatty acid (FA) composition in flax.
      In the present study, we looked at promoter structural variations of six FA
      desaturase genes and their relative expression throughout seed development.
      Computational analysis of the nucleotide sequences of the sad1, sad2, fad2a,
      fad2b, fad3a and fad3b promoters showed several basic transcriptional elements
      including CAAT and TATA boxes, and several putative target-binding sites for
      transcription factors, which have been reported to be involved in the regulation
      of lipid metabolism. Using semi-quantitative reverse transcriptase PCR, the
      expression patterns throughout seed development of the six FA desaturase genes
      were measured in six flax genotypes that differed for FA composition but that
      carried the same desaturase isoforms. FA composition data were determined by
      phenotyping the field grown genotypes over four years in two environments. All
      six genes displayed a bell-shaped pattern of expression peaking at 20 or 24 days
      after anthesis. Sad2 was the most highly expressed. The expression of all six
      desaturase genes did not differ significantly between genotypes (P = 0.1400),
      hence there were no correlations between FA desaturase gene expression and
      variations in FA composition in relatively low, intermediate and high linolenic
      acid genotypes expressing identical isoforms for all six desaturases. These
      results provide further clues towards understanding the genetic factors
      responsible for FA composition in flax.

PMID- 24871200
TI  - Genome engineering empowers the diatom Phaeodactylum tricornutum for
      biotechnology.
AB  - Diatoms, a major group of photosynthetic microalgae, have a high biotechnological
      potential that has not been fully exploited because of the paucity of available
      genetic tools. Here we demonstrate targeted and stable modifications of the
      genome of the marine diatom Phaeodactylum tricornutum, using both meganucleases
      and TALE nucleases. When nuclease-encoding constructs are co-transformed with a
      selectable marker, high frequencies of genome modifications are readily attained
      with 56 and 27% of the colonies exhibiting targeted mutagenesis or targeted gene
      insertion, respectively. The generation of an enhanced lipid-producing strain (45
      fold increase in triacylglycerol accumulation) through the disruption of the UDP
      glucose pyrophosphorylase gene exemplifies the power of genome engineering to
      harness diatoms for biofuel production. 

PMID- 24871201
TI  - Recent advances in deep-sea natural products.
AB  - Covering: 2009 to 2013. This review covers the 188 novel marine natural products
      described since 2008, from deep-water (50->5000 m) marine fauna including
      bryozoa, chordata, cnidaria, echinodermata, microorganisms, mollusca and
      porifera. The structures of the new compounds and details of the source organism,
      depth of collection and country of origin are presented, along with any relevant
      biological activities of the metabolites. Where reported, synthetic studies on
      the deep-sea natural products have also been included. Most strikingly, 75% of
      the compounds were reported to possess bioactivity, with almost half exhibiting
      low micromolar cytotoxicity towards a range of human cancer cell lines, along
      with a significant increase in the number of microbial deep-sea natural products
      reported.

PMID- 24871203
TI  - Total flavonoids of litsea coreana enhance the cytotoxicity of oxaliplatin by
      increasing gap junction intercellular communication.
AB  - Oxaliplatin is widely used in the treatment of variety of cancers, including
      cancer of the testis and colorectum. Gap junctions (GJs) can amplify the
      cytotoxicity of antinoeoplastic drugs through the bystander effect in different
      cancer cells. In this study, we demonstrate that total flavonoids of litsea
      coreana (TFLC), one extract from the dried leaves of litsea coreana leve,
      increase the cytotoxicity of oxaliplatin in mouse testicular cancer I-10 cells.
      We found that cell survival was substantially decreased only when functional GJs
      formed in I-10 cells. TFLC increased oxaliplatin cytotoxity (inducing cell death
      and apoptosis) by enhancing gap junction intercellular communication (GJIC)
      through elevated Cx43 protein expression. Furthermore, apoptosis-related protein
      (Bax, Bcl-2, caspase-3/9) results showed that the Bax/Bcl-2 ratio and activated
      caspase-3/9 increased when TFLC was used compared with treatment with oxaliplatin
      alone, which suggests that the mechanism of increased oxaliplatin-induced
      apoptosis was through the mitochondrial pathway. These results demonstrate that
      TFLC can enhance the cytotoxicity of oxaliplatin, and that these processes may be
      regulated in testicular tumor cells through GJ-mediated regulation of tumor cell
      apoptosis. 

PMID- 24871202
TI  - Brain structure and functional connectivity associated with pornography
      consumption: the brain on porn.
AB  - IMPORTANCE: Since pornography appeared on the Internet, the accessibility,
      affordability, and anonymity of consuming visual sexual stimuli have increased
      and attracted millions of users. Based on the assumption that pornography
      consumption bears resemblance with reward-seeking behavior, novelty-seeking
      behavior, and addictive behavior, we hypothesized alterations of the
      frontostriatal network in frequent users. OBJECTIVE: To determine whether
      frequent pornography consumption is associated with the frontostriatal network.
      DESIGN, SETTING, AND PARTICIPANTS: In a study conducted at the Max Planck
      Institute for Human Development in Berlin, Germany, 64 healthy male adults
      covering a wide range of pornography consumption reported hours of pornography
      consumption per week. Pornography consumption was associated with neural
      structure, task-related activation, and functional resting-state connectivity.
      MAIN OUTCOMES AND MEASURES: Gray matter volume of the brain was measured by voxel
      based morphometry and resting state functional connectivity was measured on 3-T
      magnetic resonance imaging scans. RESULTS: We found a significant negative
      association between reported pornography hours per week and gray matter volume in
      the right caudate (P < .001, corrected for multiple comparisons) as well as with
      functional activity during a sexual cue-reactivity paradigm in the left putamen
      (P < .001). Functional connectivity of the right caudate to the left dorsolateral
      prefrontal cortex was negatively associated with hours of pornography
      consumption. CONCLUSIONS AND RELEVANCE: The negative association of self-reported
      pornography consumption with the right striatum (caudate) volume, left striatum
      (putamen) activation during cue reactivity, and lower functional connectivity of
      the right caudate to the left dorsolateral prefrontal cortex could reflect change
      in neural plasticity as a consequence of an intense stimulation of the reward
      system, together with a lower top-down modulation of prefrontal cortical areas.
      Alternatively, it could be a precondition that makes pornography consumption more
      rewarding.

PMID- 24871204
TI  - Orthopaedic triaging by podiatrists: a prospective study of patient satisfaction
      and service efficiency.
AB  - BACKGROUND: The Southern Adelaide Local Health Network is serviced by one
      orthopaedic surgeon specialising in foot and ankle surgery. In 2011, the waiting
      list to see the surgeon was expanding and the need for assistance was growing.
      The Department of Podiatry agreed to provide a podiatrist to assist in the
      management of the outpatient waiting list. Although patient outcome is an
      important outcome measure, we were interested in evaluating the service with
      respect to how satisfied patients were with seeing a podiatrist. Therefore, the
      primary aim of the study was to evaluate patient satisfaction with podiatry-led
      clinics for the orthopaedic outpatient waiting list. Secondary outcomes included
      discharge rate and efficiency of care. METHODS: We prospectively recruited a
      consecutive sample discharged from the Department of Podiatry between 1 May and 1
      November 2013 to complete the Client Satisfaction Survey (CSQ-8). This survey was
      used to evaluate the satisfaction of patients following discharge from the
      Department of Podiatry. RESULTS: There were 49 patients (16 men, 33 women)
      enrolled in the survey during the 6-month period. Of the 49 patients discharged,
      21 (43%) were discharged from the outpatient waiting list. Twenty-eight patients
      (57%) were referred on to the Department of Orthopaedic Surgery for opinion and
      management. The mean (+/- s.d.) number of appointments for each patient was 1.3+/
      0.6. Overall, patients were very satisfied with the assessment and/or treatment
      they received. CONCLUSION: A podiatrist, working at an extended scope of practice
      and in collaboration with an orthopaedic surgeon, can successfully and
      efficiently assess and treat patients on an orthopaedic outpatient waiting list.
      Patients generally reported a high level of satisfaction with the process and
      would return to the clinic again if necessary. Hospital networks wanting to
      efficiently reduce waiting lists may endorse task substitution for appropriately
      skilled podiatrists.

PMID- 24871205
TI  - Gastric dilatation and volvulus in a brachycephalic dog with hiatal hernia.
AB  - A brachycephalic dog was presented with an acute onset of retching and abdominal
      discomfort. The dog had a chronic history of stertor and exercise intolerance
      suggestive of brachycephalic airway obstructive syndrome. Radiographs were
      consistent with a Type II hiatal hernia. The dog was referred and within hours of
      admission became acutely painful and developed tympanic abdominal distension. A
      right lateral abdominal radiograph confirmed gastric dilatation and volvulus with
      herniation of the pylorus through the hiatus. An emergency exploratory coeliotomy
      was performed, during which the stomach was derotated, and an incisional
      gastropexy, herniorrhaphy and splenectomy were performed. A staphylectomy was
      performed immediately following the exploratory coeliotomy. The dog recovered
      uneventfully. Gastric dilatation and volvulus is a potentially life-threatening
      complication that can occur in dogs with Type II hiatal hernia and should be
      considered a surgical emergency. 

PMID- 24871206
TI  - Inhibitory effects of beta-chamigrenal, isolated from the fruits of Schisandra
      chinensis, on lipopolysaccharide-induced nitric oxide and prostaglandin E2
      production in RAW 264.7 macrophages [corrected].
AB  - Much is known about the bioactive properties of lignans from the fruits of
      Schisandra chinensis. However, very little work has been done to determine the
      properties of sesquiterpenes in the fruits of S. chinensis. The aim of the
      present study was to investigate the anti-inflammatory potential of new
      sesquiterpenes (beta-chamigrenal, beta-chamigrenic acid, alpha-ylangenol, and
      alpha-ylangenyl acetate) isolated from the fruits of S. chinensis and to explore
      their effect on macrophages stimulated with lipopolysaccharide. Of these four
      sesquiterpenes, beta-chamigrenal most significantly suppressed lipopolysaccharide
      induced nitric oxide and prostaglandin E2 production in RAW 264.7 macrophages
      (47.21 +/- 4.54 % and 51.61 +/- 3.95 % at 50 uM, respectively). Molecularly, the
      inhibitory activity of beta-chamigrenal on nitric oxide production was mediated
      by suppressing inducible nitric oxide synthase activity but not its expression.
      In the prostaglandin E2 synthesis pathway, beta-chamigrenal prevented the
      upregulation of inducible microsomal prostaglandin E synthase-1 expression after
      stimulation with lipopolysaccharide. Conversely, beta-chamigrenal had no effect
      on the expression and enzyme activity of cyclooxygenase-2. In addition, the
      expression of early growth response factor-1, a key transcription factor of
      microsomal prostaglandin E synthase-1 expression, was inhibited by beta
      chamigrenal. These results may suggest a possible anti-inflammatory activity of
      beta-chamigrenal which has to be proven in in vivo experiments.

PMID- 24871207
TI  - Anti-inflammatory and antinociceptive activities of azadirachtin in mice.
AB  - Azadirachta indica (Meliaceae) extracts have been reported to exhibit anti
      inflammatory and antinociceptive properties. However, the activities of
      azadirachtin, a limonoid and the major bioactive compound found in the extracts,
      have been poorly investigated in animal models. In the present study, we
      investigated the effects induced by azadirachtin in experimental models of pain
      and inflammation in mice. Carrageenan-induced paw edema and fibrovascular tissue
      growth induced by subcutaneous cotton pellet implantation were used to
      investigate the anti-inflammatory activity of azadirachtin in mice. Zymosan
      induced writhing and hot plate tests were employed to evaluate the
      antinociceptive activity. To explore putative mechanisms of action, the level of
      tumor necrosis factor-alpha in inflammatory tissue was measured and the effect
      induced by opioidergic and serotonergic antagonists was evaluated. Previous per
      os (p. o.) administration of azadirachtin (120 mg/kg) significantly reduced the
      acute paw edema induced by carrageenan. However, the concomitant increase of the
      paw concentration of tumor necrosis factor-alpha induced by this inflammatory
      stimulus was not reduced by azadirachtin. In addition to inhibiting the acute paw
      edema induced by carrageenan, azadirachtin (6, 60, and 120 mg/kg) inhibited the
      proliferative phase of the inflammatory response, as demonstrated by the reduced
      formation of fibrovascular tissue growth. Azadirachtin (120 mg/kg) also inhibited
      the nociceptive response in models of nociceptive (hot plate) and inflammatory
      (writhing induced by zymosan) pain. The activity of azadirachtin (120 mg/kg) in
      the model of nociceptive pain was attenuated by a nonselective opioid antagonist,
      naltrexone (10 mg/kg, i. p.), but not by a nonselective serotonergic antagonist,
      cyproheptadine. In conclusion, this study demonstrates the activity of
      azadirachtin in experimental models of nociceptive and inflammatory pain, and
      also in models of acute and chronic inflammation. Finally, multiple mechanisms,
      including the inhibition of the production of inflammatory mediators and
      activation of endogenous opioid pathways, may mediate azadirachtin activities in
      experimental models of inflammation and pain.

PMID- 24871209
TI  - Restricted open-shell configuration interaction cluster calculations of the L
      edge X-ray absorption study of TiO(2) and CaF(2) solids.
AB  - X-ray metal L-edge spectroscopy has proven to be a powerful technique for
      investigating the electronic structure of transition-metal centers in
      coordination compounds and extended solid systems. We have recently proposed the
      Restricted Open-Shell Configuration Interaction Singles (ROCIS) method and its
      density functional theory variant (DFT/ROCIS) as methods of general applicability
      for interpreting such spectra. In this work, we apply the ROCIS and DFT/ROCIS
      methods for the investigation of cluster systems in order to interpret the Ca and
      Ti L-edge spectra of CaF2 and TiO2 (rutile and anatase), respectively. Cluster
      models with up to 23 metallic centers are considered together with the hydrogen
      saturation and embedding techniques to represent the extended ionic and covalent
      bulk environments of CaF2 and TiO2. The experimentally probed metal coordination
      environment is discussed in detail. The influence of local as well as nonlocal
      effects on the intensity mechanism is investigated. In addition, the physical
      origin of the observed spectral features is qualitatively and quantitatively
      discussed through decomposition of the dominant relativistic states in terms of
      leading individual 2p-3d excitations. This contribution serves as an important
      reference for future applications of ROCIS and DFT/ROCIS methods in the field of
      metal L-edge spectroscopy in solid-state chemistry. 

PMID- 24871208
TI  - [Radiotherapy for solitary plasmacytoma and multiple myeloma].
AB  - Solitary plasmacytoma and multiple myeloma require a differentiated radiotherapy.
      The irradiation for plasmacytoma with an adequate total dose (medullary 40-50 Gy
      or extramedullary 50-60 Gy) leads to a high degree of local control with a low
      rate of side effects. In cases of multiple myeloma radiotherapy will achieve
      effective palliation, both in terms of recalcification as well as reduction of
      neurological symptoms and analgesia. In terms of analgesia the rule is the higher
      the single dose fraction the faster the reduction of pain. As part of a
      conditioning treatment prior to stem cell transplantation radiotherapy
      contributes to the establishment of a graft versus myeloma effect (GVM). 

PMID- 24871211
TI  - Molecular dynamics simulation of amorphous hydroxypropyl-methylcellulose acetate
      succinate (HPMCAS): polymer model development, water distribution, and
      plasticization.
AB  - Molecular models for HPMCAS polymer have been developed for molecular dynamics
      (MD) simulation that attempt to mimic the complex substitution patterns in HPMCAS
      observed experimentally. These molecular models were utilized to create amorphous
      HPMCAS solids by cooling of the polymeric melts at different water contents to
      explore the influence of water on molecular mobility, which plays a critical role
      in stability and drug release from HPMCAS-based solid matrices. The densities
      found for the simulated amorphous HPMCAS were 1.295, 1.287, and 1.276 g/cm(3) at
      0.7, 5.7, and 13.2% w/w water, indicating swelling of the polymer with increasing
      water content. These densities compare favorably with the experimental density of
      1.285 g/cm(3) for commercial HPMCAS-(AQOAT AS-MF) supporting the present HPMCAS
      models as a realistic representation of amorphous HPMCAS solids. Water molecules
      were observed to be mostly isolated from each other at a low water content (0.7%
      w/w), while clusters or strands of water were pervasive and broadly distributed
      in size at 13.2% w/w water. The average number of first-shell water molecules
      (n(w)) increased from 0.17 to 3.5, though the latter is still far below that
      (8.9) expected for the onset of a separate water phase. Increasing water content
      from 0.7 to 13.2% w/w was found to reduce the T(g) by ~81 K, similar to
      experimental observations. Plasticization with increasing water content resulted
      in increasing polymer mobility and water diffusivity. From 0.7 to 13.2% w/w
      water, the apparent water diffusivity increased from 1.1 * 10(-9) to 7.0 * 10(-8)
      cm(2)/s, though non-Einsteinian behavior persisted at all water contents
      explored. This and the water trajectories in the polymers suggest that water
      diffusion at 0.7% w/w water follows a "hopping" mechanism. At a higher water
      content (13.2% w/w) water diffusion follows dual diffusive processes: (1) fast
      water motions within water clusters; and (2) slower diffusion through the more
      rigid polymer matrix.

PMID- 24871212
TI  - Detection and molecular characterization of Mycobacterium microti isolates in
      wild boar from northern Italy.
AB  - Approximately 23,000 hunter-harvested wild boars from the pre-Alpine area of
      northern Italy were examined for tuberculosis over a 9-year period (2003 to
      2011). Retropharyngeal and mandibular lymph nodes from the wild boars were
      examined grossly, and 1,151 of the lymph nodes were analyzed in our laboratory by
      histology (728 samples) and culture isolation (819 samples). Mycobacterium
      tuberculosis complex (MTBC)-specific PCR (1,142 samples) was used for molecular
      level detection in tissue samples, as was a gyrB restriction fragment length
      polymorphism (RFLP) assay (322 samples). Lesions compatible with tuberculosis and
      indistinguishable from those described in cases of Mycobacterium bovis infection
      had been observed since 2003. Mycobacterium microti was identified directly in
      256 tissue samples by the adopted molecular approaches. However, only 26 M.
      microti strains were obtained by culture isolation due to the well-known
      difficulties in isolating this slow-growing mycobacterium. During 2006, a
      prevalence study was performed in two provinces of the area, and the diffusion of
      M. microti was calculated to be 5.8% (95% confidence intervals surrounding the
      estimated prevalences [CIP95%], 3.94 to 7.68%). Over the following years (2007 to
      2011), the presence of M. microti appeared to be stable. All isolates were
      genotyped by spoligotyping and exact tandem repeat analysis (ETR types A to F).
      In addition to the typical vole type (SB0118), a new spoligotype lacking the 43
      spacers was found. Spoligotyping was also applied directly to tissue samples, and
      a geographical cluster distribution of the two spoligotypes was observed. This is
      the first report studying the diffusion and genetic variability of M. microti in
      wild boar. 

PMID- 24871213
TI  - Impact of antimicrobial stewardship intervention on coagulase-negative
      Staphylococcus blood cultures in conjunction with rapid diagnostic testing.
AB  - Rapid diagnostic testing with matrix-assisted laser desorption ionization-time of
      flight (MALDI-TOF) decreases the time to organism identification by 24 to 36 h
      compared to the amount of time required by conventional methods. However, there
      are limited data evaluating the impact of MALDI-TOF with real-time antimicrobial
      stewardship team (AST) review and intervention on antimicrobial prescribing and
      outcomes for patients with bacteremia and blood cultures contaminated with
      coagulase-negative Staphylococcus (CoNS). A quasiexperimental study was conducted
      to analyze the impact of rapid diagnostic testing with MALDI-TOF plus AST review
      and intervention for adult hospitalized patients with blood cultures positive for
      CoNS. Antibiotic prescribing patterns and clinical outcomes were compared before
      and after implementation of MALDI-TOF with AST intervention for patients with
      CoNS bacteremia and CoNS contamination. A total of 324 patients with a positive
      CoNS blood culture were included; 246 were deemed to have contaminated cultures
      (117 in the preintervention group and 129 in AST the intervention group), and 78
      patients had bacteremia (46 in the preintervention group and 32 in the AST
      intervention group). No differences in demographics were seen between the groups,
      and similar rates of contamination occurred between the preintervention and AST
      intervention groups (64.3% versus 72.6%, P = 0.173). Patients with bacteremia
      were initiated on optimal therapy sooner in the AST intervention group (58.7
      versus 34.4 h, P = 0.030), which was associated with a similarly decreased
      mortality (21.7% versus 3.1%, P = 0.023). Patients with CoNS-contaminated
      cultures had similar rates of mortality, lengths of hospitalization, recurrent
      bloodstream infections, and 30-day hospital readmissions, but the AST
      intervention group had a decreased duration of unnecessary antibiotic therapy
      (1.31 versus 3.89 days, P = 0.032) and a decreased number of vancomycin trough
      assays performed (0.88 versus 1.95, P < 0.001). In patients with CoNS bacteremia,
      rapid pathogen identification integrated with real-time stewardship interventions
      improved timely organism identification and initiation of antibiotic therapy.
      Patients in the AST group with blood cultures contaminated with CoNS had
      decreased inappropriate antimicrobial prescribing and decreased unnecessary serum
      vancomycin trough assays. 

PMID- 24871214
TI  - Clinical utility of droplet digital PCR for human cytomegalovirus.
AB  - Human cytomegalovirus (CMV) has historically been the major infectious cause of
      morbidity and mortality among patients receiving hematopoietic cell or organ
      transplant. Standard care in a transplant setting involves frequent monitoring of
      CMV viral load over weeks to months to determine when antiviral treatment may be
      required. Quantitative PCR (qPCR) is the standard molecular diagnostic method for
      monitoring. Recently, digital PCR (dPCR) has shown promise in viral diagnostics,
      although current dPCR systems have lower throughput than qPCR systems. Here, we
      compare qPCR and droplet digital PCR (ddPCR) for CMV detection in patient plasma
      samples. Droplet digital PCR exhibits increased precision over qPCR at viral
      loads of >=4 log10 with equivalent sensitivity. However, retrospective analysis
      of longitudinal samples from transplant patients with CMV viral loads near
      therapeutic thresholds did not provide evidence that the improved precision of
      ddPCR would be of clinical benefit. Given the throughput advantages of current
      qPCR systems, a widespread switch to dPCR for CMV monitoring would appear
      premature. 

PMID- 24871216
TI  - Low vancomycin MICs and fecal densities reduce the sensitivity of screening
      methods for vancomycin resistance in Enterococci.
AB  - Active surveillance is part of a multifaceted approach used to prevent the spread
      of vancomycin-resistant enterococci (VRE). The impact of fecal density, the
      vancomycin MIC of the isolate, and the vancomycin concentration in liquid medium
      on test performance are uncertain. Using fecal specimens spiked with a collection
      of 18 VRE (predominantly vanB) with a wide vancomycin MIC range, we compared the
      performances of commercial chromogenic agars (CHROMagar VRE, chromID VRE,
      Brilliance VRE, and VRE Select) and 1 liquid medium (Enterococcosel enrichment
      broth) for VRE detection. The specificity of solid media was excellent; however,
      the sensitivity at 48 h varied from 78 to 94%. Screening using liquid medium was
      less sensitive than screening with solid media, particularly as the vancomycin
      content increased. Sensitivity declined (i) as the fecal VRE density decreased,
      (ii) when the media were assessed at 24 h (versus 48 h), and (iii) for isolates
      with a low vancomycin MIC (sensitivity, 25 to 75% versus 100% for isolates with
      vancomycin MIC of <16 mg/liter versus >32 mg/liter on solid medium using 10(6)
      CFU/ml of feces). Depending on local epidemiology and in particular VRE
      vancomycin MICs, the sensitivity of culture-based methods for VRE screening of
      stool or rectal specimens may be suboptimal, potentially facilitating secondary
      transmission. 

PMID- 24871215
TI  - The molecular bacterial load assay replaces solid culture for measuring early
      bactericidal response to antituberculosis treatment.
AB  - We evaluated the use of the molecular bacterial load (MBL) assay, for measuring
      viable Mycobacterium tuberculosis in sputum, in comparison with solid agar and
      liquid culture. The MBL assay provides early information on the rate of decline
      in bacterial load and has technical advantages over culture in either form. 

PMID- 24871217
TI  - Cluster of infections caused by methicillin-resistant Staphylococcus
      pseudintermedius in humans in a tertiary hospital.
AB  - The dog-associated Staphylococcus pseudintermedius is a rare pathogen in humans.
      Here we describe a cluster of infections caused by the methicillin-resistant S.
      pseudintermedius clone ST71-J-t02-II-III. It involved four elderly patients at a
      tertiary hospital. Three patients had wound infections, and the strain had a
      tendency to cause bullous skin lesions. 

PMID- 24871218
TI  - Detection of significant bacteriuria by use of the iQ200 automated urine
      microscope.
AB  - In the microbiology laboratory, there is an augmented need for rapid screening
      methods for the detection of bacteria in urine samples, since about two-thirds of
      these samples will not yield any bacteria or will yield insignificant growth when
      cultured. Thus, a reliable screening method can free up laboratory resources and
      can speed up the reporting of a negative urine result. In this study, we have
      evaluated the detection of leukocytes, bacteria, and a new sediment indicator,
      the "all small particles" (ASP), by an automated instrument, the iQ200 urine
      analyzer, to detect negative urine samples that can be excluded from culture. A
      coupled automated strip reader (iChem Velocity), enabling the detection of
      nitrite and leukocyte esterase, was tested in parallel. In total, 963 urine
      samples were processed through both conventional urine culture and the
      iQ200/iChem Velocity workstation. Using the data, a multivariate regression model
      was established, and the predicted specificity and the possible reduction in
      urine cultures were calculated for the indicators and their respective
      combinations (leukocytes plus bacteria plus ASP and leukocyte esterase plus
      nitrite). Among all options, diagnostic performance was best using the whole
      microscopic content of the sample (leukocytes plus bacteria plus ASP). By using a
      cutoff value of >= 10(4) CFU/ml for defining a positive culture, a given
      sensitivity of 95% resulted in a specificity of 61% and a reduction in urine
      cultures of 35%. By considering the indicators alone, specificity and the culture
      savings were both much less satisfactory. The regression model was also used to
      determine possible cutoff values for running the instrument as part of daily
      routine. By using a graphical representation of all combinations possible, we
      derived cutoff values for leukocyte, bacterial, and ASP count, which should
      enable the iQ200 microscope to screen out approximately one-third of the urine
      samples, significantly reducing the workload in the microbiology laboratory.

PMID- 24871219
TI  - Field study of dried blood spot specimens for HIV-1 drug resistance genotyping.
AB  - Dried blood spots (DBS) are an alternative specimen type for HIV drug resistance
      genotyping in resource-limited settings. Data relating to the impact of DBS
      storage and shipment conditions on genotyping efficiency under field conditions
      are limited. We compared the genotyping efficiencies and resistance profiles of
      DBS stored and shipped at different temperatures to those of plasma specimens
      collected in parallel from patients receiving antiretroviral therapy in Uganda.
      Plasma and four DBS cards from anti-coagulated venous blood and a fifth card from
      finger-prick blood were prepared from 103 HIV patients with a median viral load
      (VL) of 57,062 copies/ml (range, 1,081 to 2,964,191). DBS were stored at ambient
      temperature for 2 or 4 weeks or frozen at -80  degrees C and shipped from Uganda
      to the United States at ambient temperature or frozen on dry ice for genotyping
      using a broadly sensitive in-house method. Plasma (97.1%) and DBS (98.1%) stored
      and shipped frozen had similar genotyping efficiencies. DBS stored frozen (97.1%)
      or at ambient temperature for 2 weeks (93.2%) and shipped at ambient temperature
      also had similar genotyping efficiencies. Genotyping efficiency was reduced for
      DBS stored at ambient temperature for 4 weeks (89.3%, P = 0.03) or prepared from
      finger-prick blood and stored at ambient temperature for 2 weeks (77.7%, P <
      0.001) compared to DBS prepared from venous blood and handled similarly.
      Resistance profiles were similar between plasma and DBS specimens. This report
      delineates the optimal DBS collection, storage, and shipping conditions and opens
      a new avenue for cost-saving ambient-temperature DBS specimen shipments for HIV
      drug resistance (HIVDR) surveillances in resource-limited settings.

PMID- 24871220
TI  - A rapid and high-throughput screening approach for methicillin-resistant
      Staphylococcus aureus based on the combination of two different real-time PCR
      assays.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is an important pathogen that
      has been responsible for major nosocomial epidemics worldwide. For infection
      control programs, rapid and adequate detection of MRSA is of great importance. We
      developed a rapid and high-throughput molecular screening approach that consists
      of an overnight selective broth enrichment, followed by mecA, mecC, and S. aureus
      specific (SA442 gene) real-time PCR assays, with subsequent confirmation using a
      staphylococcal cassette chromosome mec element (SCCmec)-orfX-based real-time PCR
      assay (GeneOhm MRSA assay) and culture. Here, the results of the screening
      approach over a 2-year period are presented. During this period, a total of
      13,387 samples were analyzed for the presence of MRSA, 2.6% of which were
      reported as MRSA positive. No MRSA isolates carrying the mecC gene were detected
      during this study. Based on the results of the real-time PCR assays only, 95.2%
      of the samples could be reported as negative within 24 h. Furthermore, the
      performance of these real-time PCR assays was evaluated using a set of 104
      assorted MRSA isolates, which demonstrated high sensitivity for both the
      combination of mecA and mecC with SA442 and the BD GeneOhm MRSA assay (98.1% and
      97.1%, respectively). This molecular screening approach proved to be an accurate
      method for obtaining reliable negative results within 24 h after arrival at the
      laboratory and contributes to improvement of infection control programs,
      especially in areas with a low MRSA prevalence. 

PMID- 24871221
TI  - Disseminated Mycobacterium lentiflavum responsible for hemophagocytic
      lymphohistocytosis in a man with a history of heart transplantation.
AB  - Mycobacterium lentiflavum is a nontuberculous, slowly growing mycobacterium
      usually recognized as a contaminant. Here, we report a case of disseminated M.
      lentiflavum infection responsible for hemophagocytic lymphohistocytosis in a
      heart-transplanted man. 

PMID- 24871222
TI  - Pseudo-outbreak of pre-extensively drug-resistant (Pre-XDR) tuberculosis in
      Kinshasa: collateral damage caused by false detection of fluoroquinolone
      resistance by GenoType MTBDRsl.
AB  - Fluoroquinolones are the core drugs for the management of multidrug-resistant
      tuberculosis (MDR-TB). Molecular drug susceptibility testing methods provide
      considerable advantages for scaling up programmatic management and surveillance
      of drug-resistant TB. We describe here the misidentification of fluoroquinolone
      resistance by the GenoType MTBDRsl (MTBDRsl) (Hain Lifescience GmbH, Nehren,
      Germany) line probe assay (LPA) encountered during a feasibility and validation
      study for the introduction of this rapid drug susceptibility test in Kinshasa,
      Democratic Republic of Congo. The double gyrA mutation 80Ala and 90Gly
      represented 57% of all fluoroquinolone mutations identified from MDR-TB patient
      sputum samples, as confirmed by DNA sequencing. This double mutation was
      previously found to be associated with susceptibility to fluoroquinolones, yet it
      leads to absent hybridization of a wild-type band in the MTBDRsl and is thus
      falsely scored as resistance. Our findings suggest that MTBDRsl results must be
      interpreted with caution when the interpretation is based solely on the absence
      of a wild-type band without confirmation by visualization of a mutant band.
      Performance of the MTBDRsl LPA might be improved by replacing the gyrA wild-type
      probes by additional probes specific for well-documented gyrA mutations that
      confer clinically relevant resistance. 

PMID- 24871223
TI  - Lipid, fatty acid and energy density profiles of white sharks: insights into the
      feeding ecology and ecophysiology of a complex top predator.
AB  - Lipids are major sources of metabolic energy in sharks and are closely linked to
      environmental conditions and biological cycles, such as those related to diet,
      reproduction and migration. In this study, we report for the first time, the
      total lipid content, lipid class composition and fatty acid profiles of muscle
      and liver tissue of white sharks, Carcharodon carcharias, of various lengths (1.5
      3.9 m), sampled at two geographically separate areas off southern and eastern
      Australia. Muscle tissue was low in total lipid content (<0.9% wet mass, wm) and
      was dominated by phospholipids (>90% of total lipid) and polyunsaturated fatty
      acids (34+/-12% of total fatty acids). In contrast, liver was high in total lipid
      which varied between 51-81% wm and was dominated by triacylglycerols (>93%) and
      monounsaturated fatty acids (36+/-12%). With knowledge of total lipid and dry
      tissue mass, we estimated the energy density of muscle (18.4+/-0.1 kJ g-1 dm) and
      liver (34.1+/-3.2 kJ g-1 dm), demonstrating that white sharks have very high
      energetic requirements. High among-individual variation in these biochemical
      parameters and related trophic markers were observed, but were not related to any
      one biological or environmental factor. Signature fatty acid profiles suggest
      that white sharks over the size range examined are generalist predators with
      fish, elasmobranchs and mammalian blubber all contributing to the diet. The
      ecological applications and physiological influences of lipids in white sharks
      are discussed along with recommendations for future research, including the use
      of non-lethal sampling to examine the nutritional condition, energetics and
      dietary relationships among and between individuals. Such knowledge is
      fundamental to better understand the implications of environmental perturbations
      on this iconic and threatened species. 

PMID- 24871224
TI  - A phylogeny of the family Poritidae (Cnidaria, Scleractinia) based on molecular
      and morphological analyses.
AB  - The family Poritidae formerly included 6 genera: Alveopora, Goniopora,
      Machadoporites, Porites, Poritipora, and Stylaraea. Morphologically, the genera
      can be differentiated based on the number of tentacles, the number of septa and
      their arrangement, the length of the polyp column, and the diameter of the
      corallites. However, the phylogenetic relationships within and between the genera
      are unknown or contentious. On the one hand, Alveopora has been transferred to
      the Acroporidae recently because it was shown to be more closely related to this
      family than to the Poritidae by previous molecular studies. On the other hand,
      Goniopora is morphologically similar to 2 recently described genera,
      Machadoporites and Poritipora, particularly with regard to the number of septa
      (approximately 24), but they have not yet been investigated at the molecular
      level. In this study, we analyzed 93 samples from all 5 poritid genera and
      Alveopora using 2 genetic markers (the barcoding region of the mitochondrial COI
      and the ITS region of the nuclear rDNA) to investigate their phylogenetic
      relationships and to revise their taxonomy. The reconstructed molecular trees
      confirmed that Alveopora is genetically distant from all poritid genera but
      closely related to the family Acroporidae, whereas the other genera are
      genetically closely related. The molecular trees also revealed that
      Machadoporites and Poritipora were indistinguishable from Goniopora. However,
      Goniopora stutchburyi was genetically isolated from the other congeneric species
      and formed a sister group to Goniopora together with Porites and Stylaraea, thus
      suggesting that 24 septa could be an ancestral feature in the Poritidae. Based on
      these data, we move G. stutchburyi into a new genus, Bernardpora gen. nov.,
      whereas Machadoporites and Poritipora are merged with Goniopora. 

PMID- 24871227
TI  - The roles of cornea and axial length in corneal hysteresis among emmetropes and
      high myopes: a pilot study.
AB  - PURPOSE: To observe the roles of cornea and axial length (AL) in corneal
      hysteresis (CH) among emmetropes and high myopes. MATERIALS AND METHODS: The CH,
      corneal resistance factor (CRF) and corneal-compensated intraocular pressure
      (IOPcc) of 40 young emmetropes (spherical equivalent +/-0.50 D) and 40 age
      matched high myopes (-6D or more) were measured by the Ocular Response Analyzer.
      AL was measured using a partial coherence interferometer. The mean keratometry
      reading (meanK) and corneal volume (CV) in 4 zones were measured using the
      Pentacam. Full stromal thickness (FST) and epithelial and Bowman's thicknesses
      (Epi + BT) were evaluated using confocal microscopy. Valid confocal microscopic
      results from the more emmetropic eyes of 30 emmetropes and the more myopic eyes
      of 27 high myopes were studied. RESULTS: High myopes exhibited significantly
      longer AL (27.34 +/- 0.90 mm versus 23.71 +/- 0.79 mm), lower CH (10.17 +/- 1.38
      mmHg versus 11.11 +/- 1.25 mmHg), and higher IOPcc (16.50 +/- 3.05 mmHg versus
      13.91 +/- 2.49 mmHg) compared with emmetropes. The 2 groups showed similar CRF,
      CVs, meanK, FST and Epi + BT. By combining the results of both groups, CH and CRF
      were significantly correlated with FST (r(2)= 0.368 and r(2 )= 0.408,
      respectively), CVs (r(2)= 0.251-0.391 and r(2)= 0.201-0.346, respectively), but
      not with Epi + BT or meanK. Furthermore, AL and IOPcc were significantly
      correlated with CH (r(2)= 0.112 and r(2)= 0.161, respectively) but not with CRF.
      The multivariate analysis indicated that FST (standardized coefficients, beta =
      0.591) and CV (beta = 0.575) had stronger association than IOPcc and AL for CH.
      CONCLUSIONS: High myopes exhibited lower CH than emmetropes. Although CH had
      stronger correlation with FST than AL, it might contain the biomechanical
      properties of components other than the cornea.

PMID- 24871229
TI  - Hydrophobic radicals embedded in neutral surfactants for dynamic nuclear
      polarization of aqueous environments at 9.4 Tesla.
AB  - We show how large DNP enhancements of NMR signals can be obtained from several
      hydrophobic radicals that are solubilised in aqueous environments by a variety of
      biologically compatible neutral amphiphiles. In particular we show that the bi
      radical TEKPOL can be incorporated into micelles formed by the surfactant
      polysorbate 80 (Tween-80), where we obtain large DNP enhancements (~60) at 9.4 T
      and ~100 K. 

PMID- 24871228
TI  - Controlling health costs: physician responses to patient expectations for medical
      care.
AB  - BACKGROUND: Physicians have dual responsibilities to make medical decisions that
      serve their patients' best interests but also utilize health care resources
      wisely. Their ability to practice cost-consciously is particularly challenged
      when faced with patient expectations or requests for medical services that may be
      unnecessary. OBJECTIVE: To understand how physicians consider health care
      resources and the strategies they use to exercise cost-consciousness in response
      to patient expectations and requests for medical care. DESIGN: Exploratory,
      qualitative focus groups of practicing physicians were conducted. Participants
      were encouraged to discuss their perceptions of resource constraints, and
      experiences with redundant, unnecessary and marginally beneficial services, and
      were asked about patient requests or expectations for particular services.
      PARTICIPANTS: Sixty-two physicians representing a variety of specialties and
      practice types participated in nine focus groups in Michigan, Ohio, and Minnesota
      in 2012 MEASUREMENTS: Iterative thematic content analysis of focus group
      transcripts PRINCIPAL FINDINGS: Physicians reported making trade-offs between a
      variety of financial and nonfinancial resources, considering not only the
      relative cost of medical decisions and alternative services, but the time and
      convenience of patients, their own time constraints, as well as the logistics of
      maintaining a successful practice. They described strategies and techniques to
      educate patients, build trust, or substitute less costly alternatives when
      appropriate, often adapting their management to the individual patient and
      clinical environment. CONCLUSIONS: Physicians often make nuanced trade-offs in
      clinical practice aimed at efficient resource use within a complex flow of
      clinical work and patient expectations. Understanding the challenges faced by
      physicians and the strategies they use to exercise cost-consciousness provides
      insight into policy measures that will address physician's roles in health care
      resource use.

PMID- 24871230
TI  - Use of negative-pressure wound therapy in breast tissues: evaluation of the
      literature.
AB  - BACKGROUND: Negative-pressure wound therapy (NPWT) has been suggetsed to have a
      positive impact on the healing of sternal or extremity wounds. However, few data
      deriving from breast surgery have been published. We evaluated the available
      literature regarding the effectiveness of NPWT systems in the healing of breast
      tissues. METHODS: The PubMed and Scopus databases were searched systematically,
      and all studies that provided relevant data were considered eligible for
      inclusion in the review. Twenty studies (154 female patients) met the inclusion
      criteria (four cohort studies, one case series, and 15 case reports). RESULTS:
      The NPWT system was used alone in 17 patients and in combination with other
      techniques in the remaining 137. The lesion was secondary to plastic surgery in
      107 women, other operations in 40 women (38 of them for breast cancer), and
      primary breast infection in seven women. Infections (including necrotizing
      fasciitis), pyoderma gangrenosum, and necrosis were among the most common
      complications for which NPWT was used. In total, 150 of 154 patients receiving
      NPWT healed completely. Two patients died before complete closure for reasons
      unrelated to the wound, and NPWT failed in two patients who healed later with
      muscle flap coverage. CONCLUSION: The scant published evidence suggests that NPWT
      systems might be useful in the healing of complicated breast wounds. However,
      larger studies are needed to investigate the effectiveness of this system further
      before it is established in breast surgery.

PMID- 24871231
TI  - Banning the hiring of tobacco users: where's the fire?
AB  - This commentary addresses the article in this issue by Huddle and colleagues
      concerning the implementation of policies by the University of Alabama at
      Birmingham (UAB) School of Medicine and other academic health centers to not hire
      users of tobacco products. Huddle and colleagues explore the basis for such
      policies and find that even though institutions may be within their rights to
      implement such policies, the policies are inconsistent with the societal role of
      an academic health center as a caregiving institution. They see a potential for
      discrimination, as contemporary users of tobacco are more likely to have less
      education and lower incomes than nonusers.The authors of this commentary review
      the arguments for and against such policies and explore the complexities of the
      implementation of such a policy by a state institution. They express concern that
      a state institution has chosen not to hire state residents who use tobacco
      products, which are legal. The authors also explore the potentially
      discriminatory aspects of such policies and possible implications of these
      policies in the context of rights and legal frameworks.The academic medicine
      community must learn from the experience that will follow from such policies as
      well as from other state and nonstate institutions that have implemented similar
      employment policies. Huddle and colleagues have provided a thoughtful
      contribution to a complex and inevitably continuing discussion.

PMID- 24871232
TI  - Medical specialty boards can help measure graduate medical education outcomes.
AB  - U.S. graduate medical education (GME) training institutions are under increasing
      scrutiny to measure program outcomes as a demonstration of accountability for the
      sizeable funding they receive from the federal government. The Accreditation
      Council for Graduate Medical Education (ACGME) is a potential agent of measuring
      GME accountability but has no interaction with physicians after residency
      training is completed. American Board of Medical Specialty (ABMS) member boards
      interact with physicians throughout their careers through maintenance of
      certification (MOC) and are a potential source of valuable data on physician
      competency and quality of care, both of which could be used to measure GME
      accountability.The authors propose that ABMS boards and the ACGME deepen their
      existing relationship to better assess residency training outcomes. ABMS boards
      have a wealth of data on physicians collected as a by-product of MOC and business
      operations. Further, many ABMS boards collect practice demographics and scope-of
      practice information through MOC enrollment surveys or recertification
      examination questionnaires. These data are potentially valuable in helping
      residencies know what their graduates are doing in practice. Part 4 of MOC
      generally involves assessment of the quality of care delivered in practice, and
      ABMS boards could share these deidentified data with the ACGME and residency
      programs to provide direct feedback on the practice outcomes of graduates.ABMS
      member boards and the ACGME should broaden their long-standing relationship to
      further develop shared roles and data-sharing mechanisms to better inform
      residencies and the public about GME training outcomes. 

PMID- 24871233
TI  - Health care institutions should not exclude smokers from employment.
AB  - Some health care institutions, including academic health centers, have adopted
      policies excluding smokers from employment. Claims advanced on behalf of these
      policies include financial savings from reduced health costs and absenteeism as
      well as advantages consonant with their message of healthy living. The authors
      suggest that the institutional savings from these policies are speculative and
      unproven. Also, in settings where large medical schools operate, it is likely to
      be the poor, including members of minority groups, who, under an employee smoker
      ban, will lose the opportunity to work for an employer that offers health
      insurance and other benefits. In response to the incentives created by such bans,
      some will quit smoking, but most will not. Thus, at the community level, employee
      smoker bans are more likely to be harmful than beneficial.Although private
      businesses may rightly choose not to hire smokers in the 19 states where such
      policies are legal, health care institutions, including academic health centers,
      should consider hiring choices in light of the values they profess. The
      traditional values of medicine include service to all persons in need, even when
      illness results from addiction or unsafe behavior. Secular academic communities
      require a shared dedication to discovery without requiring strict conformity of
      private behavior or belief. The authors conclude that for health care
      institutions, policies of hiring smokers and helping them to quit are both
      prudent and expressive of the norms of medical care, such as inclusion,
      compassion, and fellowship, that academic health professionals seek to honor.

PMID- 24871234
TI  - Financial sustainability of academic health centers: identifying challenges and
      strategic responses.
AB  - Academic health centers (AHCs) play a vital role in the health care system. The
      training of health care personnel and delivery of health care services,
      especially to the most complex and financially challenged patients, has been a
      responsibility increasingly shouldered by AHCs over the years. Additionally, AHCs
      play a significant role in researching and developing new treatment protocols,
      including discovering and validating new health technologies. However, AHCs face
      unique financial challenges in fulfilling their social mission in the health care
      system. Reforms being implemented under the Affordable Care Act and shifting
      economic patterns are threatening the financial sustainability of AHCs.The
      authors review challenges facing AHCs, including training new health care
      professionals with fewer funding resources, disproportionate clinical care of
      complex and costly patients, charity care to uninsured and underinsured, and
      reduced research funding opportunities. Then, they provide a review of some
      potential solutions to these challenges, including new reimbursement methods,
      improvements in operational efficiency, price regulation, subsidization of
      education, improved decision making and communication, utilization of industrial
      management tools, and increasing internal and external cooperation. Devising
      solutions to the evolving problems of AHCs is crucial to improving health care
      delivery in the United States. Most likely, a combination of market, government,
      and system reforms will be needed to improve the viability of AHCs and assist
      them in fulfilling their social and organizational missions.

PMID- 24871235
TI  - Physician assistants and the disclosure of medical error.
AB  - Evolving state law, professional societies, and national guidelines, including
      those of the American Medical Association and Joint Commission, recommend that
      patients receive transparent communication when a medical error occurs.
      Recommendations for error disclosure typically consist of an explanation that an
      error has occurred, delivery of an explicit apology, an explanation of the facts
      around the event, its medical ramifications and how care will be managed, and a
      description of how similar errors will be prevented in the future. Although error
      disclosure is widely endorsed in the medical and nursing literature, there is
      little discussion of the unique role that the physician assistant (PA) might play
      in these interactions. PAs are trained in the medical model and technically
      practice under the supervision of a physician. They are also commonly integrated
      into interprofessional health care teams in surgical and urgent care settings. PA
      practice is characterized by widely varying degrees of provider autonomy. How PAs
      should collaborate with physicians in sensitive error disclosure conversations
      with patients is unclear. With the number of practicing PAs growing rapidly in
      nearly all domains of medicine, their role in the error disclosure process
      warrants exploration. The authors call for educational societies and accrediting
      agencies to support policy to establish guidelines for PA disclosure of error.
      They encourage medical and PA researchers to explore and report best-practice
      disclosure roles for PAs. Finally, they recommend that PA educational programs
      implement trainings in disclosure skills, and hospitals and supervising
      physicians provide and support training for practicing PAs.

PMID- 24871236
TI  - Pain medicine: The case for an independent medical specialty and training
      programs.
AB  - Over the last 30 years, pain has become one of the most dynamic areas of medicine
      and a public health issue. According to a recent Institute of Medicine report,
      pain affects approximately 100 million Americans at an estimated annual economic
      cost of $560 to $635 billion and is poorly treated overall. The American Board of
      Medical Specialties (ABMS) recognizes a pain subspecialty, but pain care delivery
      has struggled with increasing demand and developed in an inconsistent and
      uncoordinated fashion. Pain education is insufficient and highly variable.
      Multiple pain professional organizations have led to fragmentation of the field
      and lack of interdisciplinary agreement, resulting in confusion regarding who
      speaks for pain medicine. In this Perspective, the authors argue that ABMS
      recognition of pain medicine as an independent medical specialty would provide
      much needed structure and oversight for the field and would generate credibility
      for the specialty and its providers among medical peers, payers, regulatory and
      legislative agencies, and the public at large. The existing system, managed by
      three ABMS boards, largely excludes other specialties that contribute to pain
      care, fails to provide leadership from a single professional organization,
      provides suboptimal training exposure to pain medicine, and lengthens training,
      which results in inefficient use of time and educational resources. The creation
      of a primary ABMS conjoint board in pain medicine with its own residency programs
      and departments would provide better coordinated training, ensure the highest
      degree of competence of pain medicine specialists, and improve the quality of
      pain care and patient safety.

PMID- 24871237
TI  - Competencies and frameworks in interprofessional education: a comparative
      analysis.
AB  - Health professionals need preparation and support to work in collaborative
      practice teams, a requirement brought about by an aging population and increases
      in chronic and complex diseases. Therefore, health professions education has seen
      the introduction of interprofessional education (IPE) competency frameworks to
      provide a common lens through which disciplines can understand, describe, and
      implement team-based practices. Whilst an admirable aim, often this has resulted
      in more confusion with the introduction of varying definitions about similar
      constructs, particularly in relation to what IPE actually means.The authors
      explore the nature of the terms competency and framework, while critically
      appraising the concept of competency frameworks and competency-based education.
      They distinguish between competencies for health professions that are profession
      specific, those that are generic, and those that may be achieved only through
      IPE. Four IPE frameworks are compared to consider their similarities and
      differences, which ultimately influence how IPE is implemented. They are the
      Interprofessional Capability Framework (United Kingdom), the National
      Interprofessional Competency Framework (Canada), the Core Competencies for
      Interprofessional Collaborative Practice (United States), and the Curtin
      University Interprofessional Capability Framework (Australia).The authors
      highlight the need for further discussion about establishing a common language,
      strengthening ways in which academic environments work with practice
      environments, and improving the assessment of interprofessional competencies and
      teamwork, including the development of assessment tools for collaborative
      practice. They also argue that for IPE frameworks to be genuinely useful, they
      need to augment existing curricula by emphasizing outcomes that might be attained
      only through interprofessional activity.

PMID- 24871239
TI  - The clinician-educator track: training internal medicine residents as clinician
      educators.
AB  - PROBLEM: Although resident-as-teacher programs bring postgraduate trainees'
      teaching skills to a minimum threshold, intensive, longitudinal training is
      lacking for residents who wish to pursue careers in medical education. The
      authors describe the development, implementation, and preliminary assessment of
      the novel track for future clinician-educators that they introduced in the
      internal medicine residency program at Beth Israel Deaconess Medical Center in
      2010. APPROACH: Categorical medical interns with a career interest in medical
      education apply to participate in the clinician-educator track (CET) at the
      midpoint of their first postgraduate year. CET residents complete a 2.5-year
      curriculum in which they review foundations of medical education, design and
      assess new curricula, and evaluate learners and programs. They apply these skills
      in a variety of clinical settings and receive frequent feedback from faculty and
      peers. All CET residents design and implement at least one medical education
      research project. OUTCOMES: A comprehensive evaluation plan to assess the impact
      of the CET on resident teaching skills, scholarly productivity, career selection,
      and advancement is under way. A preliminary evaluation demonstrates high
      satisfaction with the track among the first cohort of CET residents, who
      graduated in 2012. Compared with residents in the traditional resident-as-teacher
      program, CET residents reported higher gains in their confidence in core medical
      education skills. NEXT STEPS: Although these preliminary data are promising, data
      will be collected over the next several years to explore whether the additional
      curricular time, faculty time, and costs and potential expansion to other
      institutions are justified.

PMID- 24871238
TI  - Development, implementation, and dissemination of the I-PASS handoff curriculum:
      A multisite educational intervention to improve patient handoffs.
AB  - Patient handoffs are a key source of communication failures and adverse events in
      hospitals. Despite Accreditation Council for Graduate Medical Education
      requirements for residency training programs to provide formal handoff skills
      training and to monitor handoffs, well-established curricula and validated skills
      assessment tools are lacking. Developing a handoff curriculum is challenging
      because of the need for standardized processes and faculty development, cultural
      resistance to change, and diverse institution- and unit-level factors. In this
      article, the authors apply a logic model to describe the process they used from
      June 2010 to February 2014 to develop, implement, and disseminate an innovative,
      comprehensive handoff curriculum in pediatric residency training programs as a
      fundamental component of the multicenter Initiative for Innovation in Pediatric
      Education-Pediatric Research in Inpatient Settings Accelerating Safe Sign-outs (I
      PASS) Study. They describe resources, activities, and outputs, and report
      preliminary learner outcomes using data from resident and faculty evaluations of
      the I-PASS Handoff Curriculum: 96% of residents and 97% of faculty agreed or
      strongly agreed that the curriculum promoted acquisition of relevant skills for
      patient care activities. They also share lessons learned that could be of value
      to others seeking to adopt a structured handoff curriculum or to develop large
      scale curricular innovations that involve redesigning firmly established
      processes. These lessons include the importance of approaching curricular
      implementation as a transformational change effort, assembling a diverse team of
      junior and senior faculty to provide opportunities for mentoring and professional
      development, and linking the educational intervention with the direct measurement
      of patient outcomes.

PMID- 24871240
TI  - Do medical school mission statements align with the nation's health care needs?
AB  - PROBLEM: To quantify the relative prevalence of traditional (education, research,
      service) and emerging (prevention, diversity, primary care, distribution, cost
      control) themes in medical school mission statements. APPROACH: In 2011, the
      authors obtained and analyzed the mission statements from 136 MD-granting and 34
      DO-granting medical schools. They read each for the presence of traditional and
      emerging themes and then compared the mission statements by category of school
      (MD-granting versus DO-granting, level of National Institutes of Health funding,
      public versus private, date of initial accreditation [before or during/after
      2000], and community-based versus non-community-based). OUTCOMES: Traditional
      themes were common in medical school mission statements-education (170; 100%),
      research (146; 86%), and service (150; 88%). Emerging themes were less common
      distribution (41; 24%), primary care (32; 19%), diversity (27; 16%), prevention
      (9; 5%), and cost control (2; 1%). DO-granting and community-based medical school
      mission statements cited the traditional theme of service and the emerging themes
      of primary care and distribution more frequently than those of MD-granting and
      non-community-based schools. NEXT STEPS: The traditional themes of education,
      research, and service dominate medical school mission statements. DO-granting and
      community-based medical schools, however, more often have incorporated the
      emerging themes of primary care and distribution. Although including emerging
      themes in a mission statement does not guarantee tangible results, omitting them
      suggests that the school has not embraced these issues. Without the engagement of
      established medical schools, the national health care problems represented by
      these emerging themes will not receive the attention they need.

PMID- 24871241
TI  - Perceptions of skill development of participants in three national career
      development programs for women faculty in academic medicine.
AB  - PURPOSE: The Association of American Medical Colleges (AAMC) and Drexel
      University College of Medicine have designed and implemented national career
      development programs (CDPs) to help women faculty acquire and strengthen skills
      needed for success in academic medicine. The authors hypothesized that skills
      women acquired in CDPs would vary by career stage and program attended. METHOD:
      In 2011, the authors surveyed a national cohort of 2,779 women listed in the AAMC
      Faculty Roster who also attended one of three CDPs (Early- and Mid-Career Women
      in Medicine Seminars, and/or Executive Leadership in Academic Medicine) between
      1988 and 2010 to examine their characteristics and CDP experiences. Participants
      indicated from a list of 16 skills whether each skill was newly acquired,
      improved, or not improved as a result of their program participation. RESULTS: Of
      2,537 eligible CDP women, 942 clicked on the link in an invitation e-mail, and
      879 (93%) completed the survey. Respondents were representative of women faculty
      in academic medicine. Participants rated the CDPs highly. Almost all reported
      gaining and/or improving skills from the CDP. Four skills predominated across all
      three programs: interpersonal skills, leadership, negotiation, and networking.
      The skills that attendees endorsed differed by respondents' career stages, more
      so than by program attended. CONCLUSIONS: Women participants perceived varying
      skills gained or improved from their attendance at the CDPs. Determining ways in
      which CDPs can support women's advancement in academic medicine requires a deeper
      understanding of what participants seek from CDPs and how they use program
      content to advance their careers.

PMID- 24871242
TI  - The gender gap in academic medicine: comparing results from a multifaceted
      intervention for stanford faculty to peer and national cohorts.
AB  - PURPOSE: To assess whether the proportion of women faculty, especially at the
      full professor rank, increased from 2004 to 2010 at Stanford University School of
      Medicine after a multifaceted intervention. METHOD: The authors surveyed gender
      composition and faculty satisfaction five to seven years after initiating a
      multifaceted intervention to expand recruitment and development of women faculty.
      The authors assessed pre/post relative change and rates of increase in women
      faculty at each rank, and faculty satisfaction; and differences in pre/post
      change and estimated rate of increase between Stanford and comparator cohorts
      (nationally and at peer institutions). RESULTS: Post intervention, women faculty
      increased by 74% (234 to 408), with assistant, associate, and full professors
      increasing by 66% (108 to 179), 87% (74 to 138), and 75% (52 to 91),
      respectively. Nationally and at peer institutions, women faculty increased by
      about 30% (30,230 to 39,200 and 4,370 to 5,754, respectively), with lower
      percentages at each rank compared with Stanford. Estimated difference (95% CI) in
      annual rate of increase was larger for Stanford versus the national cohort:
      combined ranks 0.36 (0.17 to 0.56), P = .001; full professor 0.40 (0.18 to 0.62),
      P = .001; and versus the peer cohort: combined ranks 0.29 (0.07 to 0.51), P =
      .02; full professor 0.37 (0.14 to 0.60), P = .003. Stanford women faculty
      satisfaction increased from 48% (2003) to 71% (2008). CONCLUSIONS: Increased
      satisfaction and proportion of women faculty, especially full professors, suggest
      that the intervention may ameliorate the gender gap in academic medicine.

PMID- 24871243
TI  - Predictors of physician performance on competence assessment: Findings from CPEP,
      the Center for Personalized Education for Physicians.
AB  - PURPOSE: To identify factors associated with physician performance in a
      comprehensive competence assessment. METHOD: The authors conducted a
      retrospective analysis of 683 physicians referred for assessment at the Center
      for Personalized Education for Physicians from 2000 to 2010, who were evaluated
      as either safe or unsafe to return to practice. Multivariate logistic regression
      was used to determine factors predictive of unsafe assessment outcome. Covariates
      included personal characteristics (e.g., age), practice context (e.g., solo
      practice), and referral information (e.g., previous board license action).
      RESULTS: Older physicians were more likely to have unsafe assessment outcomes
      (odds ratio [OR] = 1.07; P < .001). Board-certified individuals were less likely
      to have poor assessment outcomes (OR = 0.40; P = .003) than uncertified
      individuals. Physicians in solo practice were more likely (OR = 2.15; P = .037)
      to be deemed unsafe than physicians in other settings. Physicians with a practice
      scope that matched their training were less likely (OR = 0.29; P = .023) to have
      unsafe assessment outcomes than those whose did not. Physicians with current or
      previous board action (suspension, revocation, limitation, or stipulation) were
      more likely to be deemed unsafe (OR = 2.47; P = .003) than those without.
      CONCLUSIONS: Findings suggest that important predictors of physician performance
      on competence assessment include personal characteristics, practice context, and
      reasons for assessment referral. These findings have implications for development
      of policies and programs designed to assess risk of poor physician performance
      and quality of care improvement efforts through organizational/practice design or
      remedial education.

PMID- 24871244
TI  - The relationship between physician participation in continuing professional
      development programs and physician in-practice peer assessments.
AB  - PURPOSE: To investigate the relationship between physicians' performance, as
      evaluated through in-practice peer assessments, and their participation in
      continuing professional development (CPD). METHOD: The authors examined the
      predictive effects of participating in the CPD programs of the Royal College of
      Physicians and Surgeons of Canada and the College of Family Physicians of Canada
      one year before in-practice peer assessments conducted by the medical regulatory
      authority in Ontario, Canada, in 2008-2009. Two multivariate logistic regression
      models were used to determine whether physicians who reported participating in
      any CPD and group-based, assessment-based, and/or self-directed CPD activities
      were more or less likely to receive satisfactory assessments than physicians who
      had not. All models were adjusted for the effects of sex, age, specialty
      certification, practice location, number of patient visits per week, hours worked
      per week, and international medical graduate status. RESULTS: A total of 617
      physicians were included in the study. Analysis revealed that physicians who
      reported participating in any CPD activities were significantly more likely (odds
      ratio [OR] = 2.5; P = .021) to have satisfactory assessments than those who had
      not. In addition, physicians participating in group-based CPD activities were
      more likely to have satisfactory assessments than those who did not (OR = 2.4; P
      = .016). CONCLUSIONS: There is encouraging evidence supporting a positive
      predictive association between participating in CPD and performance on in
      practice peer assessments. The findings have potential implications for policies
      which require physicians to participate in programs of lifelong learning.

PMID- 24871245
TI  - The growth of learning communities in undergraduate medical education.
AB  - PURPOSE: To determine the presence and characteristics of learning communities
      (LCs) in undergraduate medical education. METHOD: The authors updated an earlier
      Web-based survey to assess LCs in medical education. Using a cross-sectional
      study design, they sent the survey to an LC leader or dean at each Association of
      American Medical Colleges member medical school (n = 151) between October 2011
      and March 2012. The first survey item asked respondents to indicate if their
      institution had LCs. Those with LCs were asked to provide details regarding the
      structure, governance, funding, space, curricular components, extracurricular
      activities, and areas addressed as part of the LCs. Those without LCs were asked
      only if they were considering developing them. The full survey instrument
      contained 35 items including yes/no, multiple-choice, and open-ended questions.
      The authors analyzed data using descriptive statistics and examined open-ended
      responses for recurrent themes. RESULTS: The response rate was 83.4% (126/151).
      Sixty-six schools (52.4%) had LCs. Of the 60 remaining schools without LCs, 29
      (48.3%) indicated that they were considering creating them. Of the 52 schools
      that provided the year their LCs were established, 27 (51.9%) indicated they
      began in 2007 or later. LC characteristics varied widely. CONCLUSIONS: The number
      of medical schools with LCs is increasing rapidly. LCs provide an opportunity to
      transform medical education through longitudinal relationships and mentoring.
      Further study is needed to document outcomes and best practices for LCs in
      medical education.

PMID- 24871246
TI  - Preceptors' understanding and use of role modeling to develop the CanMEDS
      competencies in residents.
AB  - PURPOSE: Role modeling by preceptors is a key strategy for training residents in
      the competencies defined within the CanMEDS conceptual framework. However, little
      is known about the extent to which preceptors are aware of the importance of role
      modeling or how they perceive and enact it in their daily interactions with
      residents. The purpose of this study was to describe how preceptors understand
      and use role modeling to develop CanMEDS competencies in residents. METHOD: In
      2010, the authors conducted a descriptive qualitative study with preceptors in
      medical, surgical, and laboratory specialties who supervised residents on a
      regular basis at the Universite Laval Faculty of Medicine (Quebec, Canada).
      Respondents participated in semistructured, individual interviews. An inductive
      thematic analysis of interview transcripts was conducted using triangulation.
      RESULTS: Most participants highlighted the importance of role modeling to support
      residents' development of the CanMEDS competencies, particularly communication,
      collaboration, and professionalism, which preceptors perceived as "less
      scientific" and the most difficult to teach. Although most participants reported
      using an implicit, unstructured role modeling process, some described more
      explicit strategies. Eight types of educational challenges in role modeling the
      CanMEDS competencies were identified, including encouraging reflective practice,
      understanding the competencies and their importance in one's specialty, and being
      aware of one's strengths and weaknesses as a clinical teacher. CONCLUSIONS:
      Preceptors are aware of the importance of role modeling competencies for
      residents, but many do so only implicitly. This study's findings are important
      for improving strategies for role modeling and for the professional development
      of preceptors.

PMID- 24871247
TI  - Searching for answers to clinical questions using google versus evidence-based
      summary resources: a randomized controlled crossover study.
AB  - PURPOSE: To compare the speed and accuracy of answering clinical questions using
      Google versus summary resources. METHOD: In 2011 and 2012, 48 internal medicine
      interns from two classes at Rutgers University Robert Wood Johnson Medical
      School, who had been trained to use three evidence-based summary resources,
      performed four-minute computer searches to answer 10 clinical questions. Half
      were randomized to initiate searches for answers to questions 1 to 5 using
      Google; the other half initiated searches using a summary resource. They then
      crossed over and used the other resource for questions 6 to 10. They documented
      the time spent searching and the resource where the answer was found. Time to
      correct response and percentage of correct responses were compared between groups
      using t test and general estimating equations. RESULTS: Of 480 questions
      administered, interns found answers for 393 (82%). Interns initiating searches in
      Google used a wider variety of resources than those starting with summary
      resources. No significant difference was found in mean time to correct response
      (138.5 seconds for Google versus 136.1 seconds for summary resource; P = .72).
      Mean correct response rate was 58.4% for Google versus 61.5% for summary resource
      (mean difference -3.1%; 95% CI -10.3% to 4.2%; P = .40). CONCLUSIONS: The authors
      found no significant differences in speed or accuracy between searches initiated
      using Google versus summary resources. Although summary resources are considered
      to provide the highest quality of evidence, improvements to allow for better
      speed and accuracy are needed.

PMID- 24871248
TI  - A tale of two cities: understanding the differences in medical professionalism
      between two Chinese cultural contexts.
AB  - PURPOSE: To compare stakeholders' constructs of medical professionalism in two
      Chinese cultural contexts. METHOD: Between November and December 2011, the
      authors adopted the nominal group technique (NGT) to elicit professional
      competencies valued by 97 medical education stakeholders at Peking Union Medical
      College (PUMC) in Beijing, China. Participants categorized the professional
      competencies according to an existing framework developed at National Taiwan
      University College of Medicine (NTUCM) in Taipei, Taiwan; they also modified and
      developed new categories for the framework. The authors analyzed NGT transcripts
      to construct a visual medical professionalism framework for PUMC and compared it
      with that of NTUCM. RESULTS: The Chinese stakeholders endorsed seven of the eight
      competencies identified in the Taiwanese framework: clinical competence,
      communication, ethics, humanism, excellence, accountability, and altruism. For
      the eighth competency, integrity, the Chinese participants preferred the term
      "morality." They also added the competencies of teamwork, self-management, health
      promotion, and economic considerations. Both frameworks differed from typical
      Western professionalism frameworks in emphasizing morality and the integration of
      social and personal roles. CONCLUSIONS: The resemblance between the Chinese and
      Taiwanese frameworks in the prominence of morality and integrity suggests the
      influence of Confucianism. The exclusively Chinese articulations of teamwork,
      health promotion, and economic considerations appear to derive from social,
      political, and economic factors unique to Mainland China. This study demonstrates
      the dynamic influence of cultural values, social history, and health care systems
      on the construction of medical professionalism frameworks and calls for further
      research to adapt global frameworks to fit specific local contexts.

PMID- 24871249
TI  - AM last page. History of medical licensure and regulation.

PMID- 24871250
TI  - Cigarette prices and smoking prevalence after a tobacco tax increase--Turkey,
      2008 and 2012.
AB  - Raising the price of tobacco products has been shown to reduce tobacco
      consumption in the United States and other high-income countries, and evidence of
      this impact has been growing for low- and middle-income countries as well. Turkey
      is a middle-income country surveyed by the Global Adult Tobacco Survey (GATS)
      twice in a 4-year period, in 2008 and 2012. During this time, the country
      introduced a policy raising its Special Consumption Tax on Tobacco and
      implemented a comprehensive tobacco control program banning smoking in public
      places, banning advertising, and introducing graphic health warnings. The higher
      tobacco tax took effect in early 2010, allowing sufficient time for subsequent
      changes in prices and smoking to be observed by the time of the 2012 GATS. This
      report uses data from GATS Turkey to examine how cigarette prices changed after
      the 2010 tax increase, describe the temporally associated changes in smoking
      prevalence, and learn whether this smoking prevalence changed more in some
      demographic groups than others. From 2008 to 2012, the average price paid for
      cigarettes increased by 42.1%, cigarettes became less affordable, and smoking
      prevalence decreased by 14.6%. The largest reduction in smoking was observed
      among persons with lower socioeconomic status (SES), highlighting the potential
      role of tax policy in reducing health disparities across socioeconomic groups. 

PMID- 24871251
TI  - Million hearts: prevalence of leading cardiovascular disease risk factors--United
      States, 2005-2012.
AB  - Each year, approximately 1.5 million U.S. adults have a heart attack or stroke,
      resulting in approximately 30 deaths every hour and, for nonfatal events, often
      leading to long-term disability. Overall, an estimated 14 million survivors of
      heart attacks and strokes are living in the United States. In 2011, the U.S.
      Department of Health and Human Services, in collaboration with nonprofit and
      private organizations, launched Million Hearts
      (http://www.millionhearts.hhs.gov), an initiative focused on implementing
      clinical and community-level evidence-based strategies to reduce cardiovascular
      disease (CVD) risk factors and prevent a total of 1 million heart attacks and
      strokes during the 5-year period 2012-2016. From 2005-2006 to the period with the
      most current data, analysis of the Million Hearts four "ABCS" clinical measures
      (for aspirin, blood pressure, cholesterol, and smoking) showed 1) no
      statistically significant change in the prevalence of aspirin use for secondary
      prevention (53.8% in 2009-2010), 2) an increase to 51.9% in the prevalence of
      blood pressure control (in 2011-2012), 3) an increase to 42.8% in the prevalence
      of cholesterol management (in 2011-2012), and 4) no statistically significant
      change in the prevalence of smoking assessment and treatment (22.2% in 2009
      2010). In addition, analysis of two community-level indicators found 1) a
      decrease in current tobacco product smoking (including cigarette, cigar, or pipe
      use) prevalence to 25.1% in 2011-2012 and 2) minimal change in mean daily sodium
      intake (3,594 mg/day in 2009-2010). Although trends in some measures are
      encouraging, further reductions of CVD risk factors will be needed to meet
      Million Hearts goals by 2017. 

PMID- 24871252
TI  - Progress toward polio eradication--Worldwide, 2013-2014.
AB  - In 1988, the World Health Assembly of the World Health Organization (WHO)
      resolved to interrupt wild poliovirus (WPV) transmission worldwide, and in 2012,
      the World Health Assembly declared the completion of global polio eradication a
      programmatic emergency for public health. By 2013, the annual number of WPV cases
      had decreased by >99% since 1988, and only three countries remained that had
      never interrupted WPV transmission: Afghanistan, Nigeria, and Pakistan. This
      report summarizes global progress toward polio eradication during 2013-2014 and
      updates previous reports. In 2013, a total of 416 WPV cases were reported
      globally from eight countries, an 86% increase from the 223 WPV cases reported
      from five countries in 2012. This upsurge in 2013 was caused by a 60% increase in
      WPV cases detected in Pakistan, and by outbreaks in five previously polio-free
      countries resulting from international spread of WPV. In 2014, as of May 20, a
      total of 82 WPV cases had been reported worldwide, compared with 34 cases during
      the same period in 2013. Polio cases caused by circulating vaccine-derived
      poliovirus (cVDPV) were detected in eight countries in 2013 and in two countries
      so far in 2014. To achieve polio eradication in the near future, further efforts
      are needed to 1) address health worker safety concerns in areas of armed conflict
      in priority countries, 2) to prevent further spread of WPV and new outbreaks
      after importation into polio-free countries, and 3) to strengthen surveillance
      globally. Based on the international spread of WPV to date in 2014, the WHO
      Director General has issued temporary recommendations to reduce further
      international exportation of WPV through vaccination of persons traveling from
      currently polio-affected countries. 

PMID- 24871253
TI  - Muscle metastasis from non-small cell lung cancer: two cases and literature
      review.
AB  - Non-small cell lung cancers (NSCLC) is the most commonly observed group among
      lung cancers. Adenocancers are histopathologically more common. Males are more
      affected than females, an effect which is directly related to smoking. They
      generally cause distant haematogenous and lymphatic metastasis. Distant
      haematogenous metastases are often seen in contralateral lung, brain, bone,
      adrenals, and liver. Muscle metastases from NSCLC are quite rare and male cases
      are more frequently affected compared to female cases. NSCLC cases with muscle
      metastasis are at the same time accompanied by distant organ metastases such as
      bone, brain, and liver. All treatment approaches are considered to be palliative
      in these cases, which are symptomatologically quite severe. In the present study,
      we presented the rarely observed cases of two male patients with muscle
      metastasis from NSCLC together with the related literature. 

PMID- 24871254
TI  - Views of general practitioners on the use of STOPP&START in primary care: a
      qualitative study.
AB  - BACKGROUND AND OBJECTIVE: STOPP (Screening Tool of Older Person's Prescriptions)
      and START (Screening Tool to Alert Doctors to Right Treatment) criteria aim at
      detecting potentially inappropriate prescribing in older people. The objective
      was to explore general practitioners' (GPs) perceptions regarding the use of the
      STOPP&START tool in their practice. DESIGN: We conducted three focus groups which
      were conveniently sampled. Vignettes with clinical cases were provided for
      discussion as well as a full version of the STOPP&START tool. Knowledge,
      strengths and weaknesses of the tool and its implementation were discussed. Two
      researchers independently performed content analysis, classifying quotes and
      creating new categories for emerging themes. RESULTS: Discussions highlighted
      incentives (e.g. systematic procedure for medication review) and barriers (e.g.
      time-consuming application) influencing the use of STOPP&START in primary care.
      Usefulness, comprehensiveness, and relevance of the tool were also questioned.
      Another important category emerging from the content analysis was the projected
      use of the tool. The GPs imagined key elements for the implementation in daily
      practice: computerized clinical decision support system, education, and
      multidisciplinary collaborations, especially at care transitions and in nursing
      homes. CONCLUSION: Despite variables views on the usefulness, comprehensiveness,
      and relevance of STOPP&START, GPs suggest the implementation of this tool in
      primary care within computerized clinical decision support systems, through
      education, and used as part of multidisciplinary collaborations.

PMID- 24871255
TI  - Nymphal antennae and antennal sensilla in Aleurodicus dispersus (Hemiptera:
      Aleyrodidae).
AB  - Whiteflies have distinct nymphal stages: their first stage is mobile, whereas the
      later immature stages are sessile. The developmental and structural changes of
      antennae and antennal sensilla in whiteflies during these stages have rarely been
      investigated. This paper describes the morphology of antennae and antennal
      sensilla in four nymphal stages of Aleurodicus dispersus based on scanning
      electron microscopy. There were significant differences found in shape and length
      of the antennae, and differences in type, number, morphological structure and
      distributional pattern of antennal sensilla in the four nymphal stages of A.
      dispersus. We found two types of sensilla on the antennae of first-instar nymph,
      three types on the third-instar nymphal antennae, four types on the second-instar
      and seven types on the fourth-instar nymphal antennae. Sensilla trichoidea (ST)
      and elevated sensilla placodea were found on the antennae of each nymphal stage,
      sensilla chaetica only occurred on the antennae of fourth-instar nymph. Sensilla
      furcatea occurred on the antennae of second- and third-instar nymphs, and
      sensilla basiconica were found on the antennae of second- and fourth-instar
      nymphs. In addition, there were sensilla campaniform and sensilla coeloconica
      found only on the antennae of fourth-instar nymph, whereas the ST of fourth
      instar nymphs included sensilla trichoidea 1 and sensilla trichoidea 2. The
      possible functions of antennal sensilla are discussed. Our results contribute to
      a better understanding of the development of the olfactory system of whitefly
      nymphal stages, and provide a basis for further exploration of chemical
      communication mechanisms between whiteflies and host plants.

PMID- 24871256
TI  - Comprehensive analysis of VQ motif-containing gene expression in rice defense
      responses to three pathogens.
AB  - KEY MESSAGE: Expression levels of rice VQ motif-containing genes in response to
      pathogen infection vary among pathogens, and some of the genes are co-expressed
      with defense-response WRKY genes. Recent studies have revealed that some VQ
      (FxxxVQxLTG) motif-containing proteins in plants partner with WRKY transcription
      factors to participate in their functions. Accumulating information suggests that
      WRKY proteins play important roles in the response of rice plants to pathogen
      infection. However, the functions of rice VQ motif-containing proteins are
      unknown. To explore whether VQ motif-containing proteins are involved in defense
      against pathogens in rice, we performed a comprehensive expression analysis of
      the genes for these proteins. The rice VQ motif-containing family consists of 40
      genes, all of which encode proteins harboring a 21-amino acid VQ-containing
      motif, which in turn contains the known VQ motif. On the basis of their
      phylogenetic relationships and tissue-specific and developmental stage-specific
      expression characteristics, we transcriptionally analyzed 13 representative genes
      in rice responses to three pathogens: Xanthomonas oryzae pv. oryzae, which causes
      bacterial blight disease; X. oryzae pv. oryzicola, which causes bacterial streak
      disease; and Magnaporthe oryzae, which causes fungal blast disease. The
      expression of some of the genes changed markedly in response to infection by at
      least one of the pathogen species, and some of the genes also showed markedly
      different expression in resistant and susceptible reactions. In addition, some
      defense-responsive VQ motif-containing genes were co-expressed with defense
      response WRKY genes. These results provide a new perspective on the putative
      roles of rice VQ motif-containing proteins and their putative WRKY partners in
      rice-pathogen interactions.

PMID- 24871258
TI  - Prevention of adolescent depression in the Spanish-speaking world.
AB  - This paper aims at presenting programs targeted at the prevention of adolescent
      depression applied with Spanish-speaking populations that have been developed in
      Spanish-speaking countries and are mostly published in Spanish. These programs
      have been developed under different cultural contexts in Spain and Latin-America.
      The main goal of this paper is to make the studies and movements of the Spanish
      speaking literature in this field accessible to the non-Spanish-speaking part of
      the research community. Therefore, after an introduction referring to possible
      cultural differences regarding depression in general and epidemiological basics,
      several programs are introduced. In total 11 programs will be shortly presented
      and discussed. After revising the programs it can be concluded that in the
      Spanish-speaking world many programs have been developed and conducted following
      current state of the art-approaches for adolescent depression prevention. Further
      research is needed especially targeting possible cultural and contextual aspects
      of prevention measures and their efficacy and efficiency. 

PMID- 24871257
TI  - The epidemiology of imported malaria in Taiwan between 2002-2013: the importance
      of sensitive surveillance and implications for pre-travel medical advice.
AB  - The purpose of this study was to assess the epidemiology of imported malaria in
      Taiwan between 2002 and 2013. We analyzed the national data recorded by the
      Taiwan Centers for Disease Control (Taiwan CDC). Malaria cases were diagnosed by
      blood films, polymerase chain reaction, or rapid diagnostic tests. The risk of re
      establishment of malarial transmission in Taiwan was assessed. A total of 229
      malaria cases were included in our analysis. All of the cases were imported. One
      hundred and ninety-two cases (84%) were diagnosed within 13 days of the start of
      symptoms/signs; 43% of these cases were acquired in Africa and 44% were acquired
      in Asia. Plasmodium falciparum was responsible for the majority (56%) of these
      cases. Travel to an endemic area was associated with the acquisition of malaria.
      The malaria importation rate was 2.36 per 1,000,000 travelers (range 1.20-5.74).
      The reproductive number under control (Rc) was 0. No endemic transmission of
      malaria in Taiwan was identified. This study suggests that a vigilant
      surveillance system, vector-control efforts, case management, and an educational
      approach focused on travelers and immigrants who visit malaria endemic countries
      are needed to prevent outbreaks and sustain the elimination of malaria in Taiwan.

PMID- 24871259
TI  - Engaging a chemical disaster community: lessons from Graniteville.
AB  - Community engagement remains a primary objective of public health practice. While
      this approach has been adopted with success in response to many community health
      issues, it is rarely adopted in chemical disaster response. Empirical research
      suggests that management of chemical disasters focuses on the emergency response
      with almost no community engagement for long-term recovery. Graniteville, an
      unincorporated and medically underserved community in South Carolina was the site
      of one of the largest chlorine exposures by a general US population. Following
      the immediate response, we sought community participation and partnered with
      community stakeholders and representatives in order to address community
      identified health and environmental concerns. Subsequently, we engaged the
      community through regular town hall meetings, harnessing community capacity,
      forming coalitions with existing local assets like churches, schools, health
      centers, and businesses, and hosting community-wide events like health picnics
      and screenings. Information obtained from these events through discussions,
      interviews, and surveys facilitated focused public health service which
      eventually transitioned to community-driven public health research. Specific
      outcomes of the community engagement efforts and steps taken to ensure
      sustainability of these efforts and outcomes will be discussed. 

PMID- 24871261
TI  - Studying children's religious knowledge: contributions of ethnography and the
      clinical-critical method.
AB  - We analyze different methodological and conceptual contributions of anthropology
      and psychogenetic theory to the research of children's religious knowledge. We
      argue that for the study of children's points of view it is possible to build an
      approach that links aspects studied by both disciplinary fields. With this aim,
      we revise some of their basic theoretical assumptions and recent reviews as well
      as their methodological proposals. Then we review the core characteristics of
      ethnography and the clinical-critical method-proposed by Piaget's psychogenetic
      theory-with the goal of stressing their potentialities as well as their
      limitations in research. We argue that within an ethnographic approach, we must
      establish certain restrictions on the clinical-critical method following basic
      premises of social anthropology. This approach lets us demonstrate the importance
      of understanding children's constructions by placing them within social relations
      that children produce and update in everyday interactions. 

PMID- 24871260
TI  - Effects of partially ionised medical oxygen, especially with O2*-, in vibration
      white finger patients.
AB  - A major symptom of hand-arm vibration syndrome is a secondary Raynaud's
      phenomenon-vibration white finger (VWF)-which results from a vasospasm of the
      digital arteries caused by work with vibration devices leading to occupational
      disease. Pharmacotherapy of VWF is often ineffective or has adverse effects. The
      aim of this work was to verify the influence of inhalation of partially ionized
      oxygen (O2*-) on peripheral blood vessels in the hands of patients with VWF.
      Ninety one (91)patients with VWF underwent four-finger adsorption
      plethysmography, and the pulse wave amplitude was recorded expressed in numeric
      parameters-called the native record. Next, a cold water test was conducted
      following with second plethysmography. The patients were divided in to the three
      groups. First and second inhaled 20-min of ionized oxygen O2*- or oxygen O2
      respectively. Thirth group was control without treatment. All three groups a
      follow-up third plethysmography-the post-therapy record. Changes in the pulse
      wave amplitudes were evaluated. Inpatients group inhaling O2*- a modest increase
      of pulse wave amplitude was observed compared to the native record; patients
      inhaling medical oxygen O2 and the control showed a undesirable decline of pulse
      wave amplitude in VWF fingers. Strong vasodilatation were more frequent in the
      group inhaling O2*- compare to O2 (p < 0.05). Peripheral vasodilatation achieved
      by inhalation of O2*- could be used for VWF treatment without undesirable side
      effect in hospital as well as at home environment. 

PMID- 24871262
TI  - PHOTO QUIZ. A 58-year-old renal transplant recipient with Fever and progressive
      dyspnea.

PMID- 24871266
TI  - Forty research issues for the redesign of animal production systems in the 21st
      century.
AB  - Agroecology offers a scientific and operational framework for redesigning animal
      production systems (APS) so that they better cope with the coming challenges.
      Grounded in the stimulation and valorization of natural processes to reduce
      inputs and pollutions in agroecosystems, it opens a challenging research agenda
      for the animal science community. In this paper, we identify key research issues
      that define this agenda. We first stress the need to assess animal robustness by
      measurable traits, to analyze trade-offs between production and adaptation traits
      at within-breed and between-breed level, and to better understand how group
      selection, epigenetics and animal learning shape performance. Second, we propose
      research on the nutritive value of alternative feed resources, including the
      environmental impacts of producing these resources and their associated non
      provisioning services. Third, we look at how the design of APS based on
      agroecological principles valorizes interactions between system components and
      promotes biological diversity at multiple scales to increase system resilience.
      Addressing such challenges requires a collection of theories and models (concept
      knowledge theory, viability theory, companion modeling, etc.). Acknowledging the
      ecology of contexts and analyzing the rationales behind traditional small-scale
      systems will increase our understanding of mechanisms contributing to the success
      or failure of agroecological practices and systems. Fourth, the large-scale
      development of agroecological products will require analysis of resistance to
      change among farmers and other actors in the food chain. Certifications and
      market-based incentives could be an important lever for the expansion of
      agroecological alternatives in APS. Finally, we question the suitability of
      current agriculture extension services and public funding mechanisms for scaling
      up agroecological practices and systems. 

PMID- 24871268
TI  - Applications of metal-organic frameworks in heterogeneous supramolecular
      catalysis.
AB  - This review summarizes the use of metal-organic frameworks (MOFs) as a versatile
      supramolecular platform to develop heterogeneous catalysts for a variety of
      organic reactions, especially for liquid-phase reactions. Following a background
      introduction about catalytic relevance to various metal-organic materials,
      crystal engineering of MOFs, characterization and evaluation methods of MOF
      catalysis, we categorize catalytic MOFs based on the types of active sites,
      including coordinatively unsaturated metal sites (CUMs), metalloligands,
      functional organic sites (FOS), as well as metal nanoparticles (MNPs) embedded in
      the cavities. Throughout the review, we emphasize the incidental or deliberate
      formation of active sites, the stability, heterogeneity and shape/size
      selectivity for MOF catalysis. Finally, we briefly introduce their relevance into
      photo- and biomimetic catalysis, and compare MOFs with other typical porous
      solids such as zeolites and mesoporous silica with regard to their different
      attributes, and provide our view on future trends and developments in MOF-based
      catalysis. 

PMID- 24871269
TI  - Fast vibrational imaging of single cells and tissues by stimulated Raman
      scattering microscopy.
AB  - Traditionally, molecules are analyzed in a test tube. Taking biochemistry as an
      example, the majority of our knowledge about cellular content comes from analysis
      of fixed cells or tissue homogenates using tools such as immunoblotting and
      liquid chromatography-mass spectrometry. These tools can indicate the presence of
      molecules but do not provide information on their location or interaction with
      each other in real time, restricting our understanding of the functions of the
      molecule under study. For real-time imaging of labeled molecules in live cells,
      fluorescence microscopy is the tool of choice. Fluorescent labels, however, are
      too bulky for small molecules such as fatty acids, amino acids, and cholesterol.
      These challenges highlight a critical need for development of chemical imaging
      platforms that allow in situ or in vivo analysis of molecules. Vibrational
      spectroscopy based on spontaneous Raman scattering is widely used for label-free
      analysis of chemical content in cells and tissues. However, the Raman process is
      a weak effect, limiting its application for fast chemical imaging of a living
      system. With high imaging speed and 3D spatial resolution, coherent Raman
      scattering microscopy is enabling a new approach for real-time vibrational
      imaging of single cells in a living system. In most experiments, coherent Raman
      processes involve two excitation fields denoted as pump at omegap and Stokes at
      omegas. When the beating frequency between the pump and Stokes fields (omegap -
      omegas) is resonant with a Raman-active molecular vibration, four major coherent
      Raman scattering processes occur simultaneously, namely, coherent anti-Stokes
      Raman scattering (CARS) at (omegap - omegas) + omegap, coherent Stokes Raman
      scattering (CSRS) at omegas - (omegap - omegas), stimulated Raman gain (SRG) at
      omegas, and stimulated Raman loss (SRL) at omegap. In SRG, the Stokes beam
      experiences a gain in intensity, whereas in SRL, the pump beam experiences a
      loss. Both SRG and SRL belong to stimulated Raman scattering (SRS), in which the
      energy difference between the pump and Stokes fields is transferred to the
      molecule for vibrational excitation. The SRS signal appears at the same
      wavelengths as the excitation fields and is commonly extracted through a phase
      sensitive detection scheme. The detected intensity change because of a Raman
      transition is proportional to Im[chi(3)]IpIs, where chi(3) represents the third
      order nonlinear susceptibility, Ip and Is stand for the intensity of the pump and
      Stokes fields. In this Account, we discuss the most recent advances in the
      technical development and enabling applications of SRS microscopy. Compared to
      CARS, the SRS contrast is free of nonresonant background. Moreover, the SRS
      intensity is linearly proportional to the density of target molecules in focus.
      For single-frequency imaging, an SRS microscope offers a speed that is ~1000
      times faster than a line-scan Raman microscope and 10,000 times faster than a
      point-scan Raman microscope. It is important to emphasize that SRS and
      spontaneous Raman scattering are complementary to each other. Spontaneous Raman
      spectroscopy covers the entire window of molecular vibrations, which allows
      extraction of subtleties via multivariate analysis. SRS offers the speed
      advantage by focusing on either a single Raman band or a defined spectral window
      of target molecules. Integrating single-frequency SRS imaging and spontaneous
      Raman spectroscopy on a single platform allows quantitative compositional
      analysis of objects inside single live cells.

PMID- 24871271
TI  - The use of videonystagmography head impulse test (VHIT) in the diagnostics of
      semicircular canal injuries in patients with vertigo.
AB  - OBJECTIVES: The aim of the study was to assess the function of semicircular canal
      in videonystagmography head impulse test (VHIT) in the patients with vertigo and
      balance disorders. MATERIAL AND METHODS: The study was performed in 135 patients
      (86 women and 49 men) aged 22-79 years, who were divided into 2 groups: I (study
      group) - 73 patients with vertigo of peripheral, central or mixed origin, II
      (control group) - 62 patients without vertigo (healthy individuals). The function
      of canal was determined on the basis of GAIN and expressed as DG/RH*100% (where
      DG is deviation of gaze and RH is rotation of head). RESULTS: In the study group
      the semicircular canal injuries were found in 37 (50.69%) patients, including 24
      (32.87%) patients with 1 injury and 13 (17.8%) patients with 2 or more injuries
      in semicircular canal. The injured anterior semicircular canal was reported 13
      times; the lateral - 9 times and the posterior - 31 times. CONCLUSIONS: In the
      study group, in the VHIT, injuries in semicircular canals were reported in
      peripheral vertigo, mixed vertigo with non-compensated and compensated function
      of the labyrinth in 50.68% cases, whereas in the caloric test dysfunction of the
      labyrinth was found in 58.49% cases.

PMID- 24871270
TI  - Solution structure and molecular determinants of hemoglobin binding of the first
      NEAT domain of IsdB in Staphylococcus aureus.
AB  - The human pathogen Staphylococcus aureus acquires heme iron from hemoglobin (Hb)
      via the action of a series of iron-regulated surface determinant (Isd) proteins.
      The cell wall anchored IsdB protein is recognized as the predominant Hb receptor,
      and is comprised of two NEAr transporter (NEAT) domains that act in concert to
      bind, extract, and transfer heme from Hb to downstream Isd proteins. Structural
      details of the NEAT 2 domain of IsdB have been investigated, but the molecular
      coordination between NEAT 2 and NEAT 1 to extract heme from hemoglobin has yet to
      be characterized. To obtain a more complete understanding of IsdB structure and
      function, we have solved the 3D solution structure of the NEAT 1 domain of IsdB
      (IsdB(N1)) spanning residues 125-272 of the full-length protein by NMR. The
      structure reveals a canonical NEAT domain fold and has particular structural
      similarity to the NEAT 1 and NEAT 2 domains of IsdH, which also interact with Hb.
      IsdB(N1) is also comprised of a short N-terminal helix, which has not been
      previously observed in other NEAT domain structures. Interestingly, the Hb
      binding region (loop 2 of IsdB(N1)) is disordered in solution. Analysis of Hb
      binding demonstrates that IsdB(N1) can bind metHb weakly and the affinity of this
      interaction is further increased by the presence of IsdB linker domain. IsdB(N1)
      loop 2 variants reveal that phenylalanine 164 (F164) of IsdB is necessary for Hb
      binding and rapid heme transfer from metHb to IsdB. Together, these findings
      provide a structural role for IsdB(N1) in enhancing the rate of extraction of
      metHb heme by the IsdB NEAT 2 domain. 

PMID- 24871272
TI  - Transfer printing of metal nanoring and nanodot arrays for use in catalytic
      reactions.
AB  - Nanoscale metal ring and dot catalyst arrays are printed over large substrate
      areas using vertically aligned carbon-based stamps with the ring- and dot-shaped
      tips. The fundamental nature of these ring and dot catalysts is successfully
      compared by applying them in diverse electrocatalytic reactions in acidic and
      alkaline media. 

PMID- 24871273
TI  - Public reporting of provider performance at a crossroads in the United States:
      summary of current barriers and recommendations on how to move forward.
AB  - Twenty-seven years after the first public release by the U.S. government of data
      on the quality of hospital care, public reporting for consumers has expanded
      substantially. Despite the growth in public reporting activities, there is
      limited evidence of their use by consumers in ways that significantly affect
      health care delivery. Support for public reporting continues, in part, because of
      the face value of transparency. The limited impact of reporting efforts is
      plausibly due to flaws in the content, design, and implementation of existing
      public reports rather than inherent limitations of reporting. Substantial work is
      still needed for public reports to achieve their potential for engaging and
      informing consumers. We present a vision statement and 10 recommendations to
      achieve this potential. 

PMID- 24871274
TI  - Use of extracts from oyster shell and soil for cultivation of Spirulina maxima.
AB  - Calcium ion and trace metals play important roles in various metabolisms of
      photosynthetic organisms. In this study, simple methods were developed to extract
      calcium ion and micronutrients from oyster shell and common soil, and the
      prepared extracts were tested as a replacement of the corresponding chemicals
      that are essential for growth of microalgae. The oyster shell and soil were
      treated with 0.1 M sodium hydroxide or with 10 % hydrogen peroxide, respectively.
      The potential application of these natural sources to cultivation was
      investigated with Spirulina maxima. When compared to standard Zarrouk medium, the
      Spirulina maxima cultivated in a modified Zarrouk media with elements from oyster
      shell and soil extract exhibited increases in biomass, chlorophyll, and
      phycocyanin by 17, 16, and 64 %, respectively. These results indicate that the
      extracts of oyster shell and soil provide sufficient amounts of calcium and trace
      metals for successful cultivation of Spirulina maxima. 

PMID- 24871275
TI  - Two-stage biogas production by co-digesting molasses wastewater and sewage
      sludge.
AB  - We evaluated the feasibility of co-digesting molasses wastewater and sewage
      sludge in a two-stage hydrogen- and methane-producing system. The highest energy
      was recovered at the 21-h hydraulic retention time (HRT) of the first hydrogenic
      reactor and at 56-h HRT of the secondary methanogenic reactor. Hence, the two
      stage system recovered 1,822 kJ from 1 L of the mixed wastes (19.7: hydrogenic
      reactor plus, 1,802 kJ L(-1): methanogenic reactor). Despite the overloaded VFA
      run with a short HRT of 56 h, the GAC-CH4 reactor increased methane production
      rate and yields due to enhanced pH buffer capacity. An RNA-based community
      analysis showed that the Ethanoligenens and Methanosaeta dominated the hydrogen
      and methane bioreactor, respectively. The two-stage system of co-digesting
      molasses and sewage sludge is particularly cost-effective due to non-pretreatment
      of sewage sludge. 

PMID- 24871276
TI  - Development of microalga Scenedesmus dimorphus mutant with higher lipid content
      by radiation breeding.
AB  - In this study, a high lipid-accumulating mutant strain of the microalgae
      Scenedesmus dimorphus was developed via radiation breeding. To induce mutant
      strain, S. dimorphus was gamma-irradiated at doses from 100 to 800 Gy, and then a
      mutant (Sd-Pm210) with 25 % increased lipid content was selected using Nile red
      staining methodology. Sd-Pm210 showed morphological changes and had higher growth
      rate compared to the wild type. From random amplified polymorphic DNA analysis,
      partial genetic modifications were also observed in Sd-Pm210. In comparisons of
      lipid content between wild type and Sd-Pm210 using thin-layer chromatography, the
      content of triacylglycerol was markedly higher in the Sd-Pm210 strain. The total
      peak area of fatty acid methyl ester was shown to have about 1.4-fold increase in
      Sd-Pm210, and major fatty acids were identified as palmitic acid, oleic acid,
      linoleic acid, and linolenic acid. To define the metabolic changes in the mutant
      strain, 2-dimensional electrophoresis was conducted. Several proteins related to
      lipid synthesis and energy metabolisms were overexpressed in the mutant strain.
      These results showed that radiation breeding can be utilized for the development
      of efficient microalgae strains for biofuel production. 

PMID- 24871277
TI  - The influence of floc size and hydraulic detention time on the performance of a
      dissolved air flotation (DAF) pilot unit in the light of a mathematical model.
AB  - The influence of floc size and hydraulic detention time on the performance of a
      dissolved air flotation (DAF) pilot unit was investigated in the light of a known
      mathematical model. The following design and operational parameters were
      considered: the hydraulic detention time (tdcz) and hydraulic loading rate in the
      contact zone, the down-flow loading rate in the clarification zone, the particle
      size distribution (d F), and the recirculation rate (p). As a reference for DAF
      performance analysis, the proposed beta.td parameter from the above mentioned
      mathematical model was employed. The results indicated that tdcz is an important
      factor in DAF performance and that d F and floc size are also determinants of DAF
      efficiency. Further, beta.td was sensitive to both design and operational
      parameters, which were varied in the DAF pilot plant. The performance of the DAF
      unit decreases with increasing beta.td values because a higher td (considering a
      fixed beta) or a higher beta (e.g., higher hydrophobicity of the flocs for a
      fixed td) would be necessary in the reaction zone to reach desired flotation
      efficiency. 

PMID- 24871278
TI  - Antiproliferative withanolides from several solanaceous species.
AB  - To date, our work on solanaceous species (Datura wrightii, Jaborosa caulescens,
      Physalis hispida, Physalis longifolia, Vassobia breviflora and Withania
      somnifera) has resulted in the isolation of 65 withanolides, 31 of which were
      new, as well as the semi-synthesis of a further 30 withanolides. Structure
      identification and MTS assay-based antiproliferative evaluation of these 95
      compounds revealed that a Delta(2)-1-oxo functionality in ring A, in conjunction
      with either a 5beta,6beta-epoxy or 5alpha-chloro-6beta-hydroxy moiety in ring B,
      is the minimum structural requirement for withanolides to produce potent
      cytotoxic activity. Such structure-activity relationship analysis also revealed
      that oxygenation (the -OH or -OR groups) at C-4, 7, 11 and 12, as well as C-14 to
      C-28, did not contribute towards the observed antiproliferative activity. Herein,
      we present a complete overview of our work as it relates to the withanolides
      reported from 1965 to 2013. 

PMID- 24871279
TI  - A taxonomic revision of genus Labrundinia Fittkau, 1962 (Diptera: Chironomidae:
      Tanypodinae).
AB  - The species of the genus Labrundinia (Diptera: Chironomidae: Tanypodinae:
      Pentaneurini) are revised, described and figured. Keys to known adult males,
      pupae and larvae are provided. Fourteen previously known species are redescribed,
      and 25 species from Neotropical region are diagnosed and described as new to
      science. These species treated are L. amandae sp. n., L. amazonica sp. n., L.
      becki Beck et Beck, L. carolae sp. n., L. costaricae sp. n., L. fera Roback, L.
      fiorelinii sp. n., L. fittkaui sp. n., L. fosteri Roback, L. hirsuta Roback, L.
      gregi sp. n., L. jasoni sp. n., L. johannseni Beck et Beck, L. kogilamae sp. n.,
      L. longipalpis Goetghebuer, L. mayaca sp. n., L. meta Roback, L. multidentata sp.
      n., L. nathani sp. n., L. neopilosella Beck et Beck, L. nicaraguensis sp. n., L.
      opela Roback, L. panamensis sp. n., L. parabecki Roback, L. parafittkaui sp. n.,
      L. parareniformis sp. n., L. paravirescens sp. n., L. paulae sp. n., L. pilosella
      Loew, L. reniformis sp. n., L. robacki sp. n., L. semicurvata sp. n., L. setosa
      sp. n., L. separata Edwards, L. sofiae sp. n., L. tenata Roback, L. trilucida sp.
      n., L. unicolor sp. n., L. virescens Beck et Beck. A diagnosis of the genus is
      presented and morphological differences to closely related genera are discussed. 

PMID- 24871280
TI  - Chilopoda Geophilomorpha of Europe: a revised list of species, with taxonomic and
      nomenclatorial notes.
AB  - An annotated list is provided for the genera and species of Chilopoda
      Geophilomorpha recorded from Europe, including Macaronesia. The list derives from
      a critical evaluation of all published information. All synonyms are also listed
      and all taxonomic and nomenclatorial novelties are discussed. Additionally, all
      available genus-group and species-group names are listed, together with type
      species and type localities respectively.To date, 452 available species-group
      names and 95 available genus-group names have been applied to European
      geophilomorphs, together with another 10 unavailable names. A total of 179
      species in 37 genera are provisionally recognized here, but the actual taxonomic
      identity of 84 of these species is uncertain because their morphology is in
      completely or imprecisely known. Another 5 species have been recorded from
      European localities but probably are not established in the wild, and another 8
      species have been reported probably only erroneously. We introduce the following
      116 new synonymies: Algerophilus hispanicus (Meinert, 1870) [= Geophilus arago
      nicus Daday, 1889], Bothriogaster signata (Kessler, 1874) [= Notiphilus taeniatus
      C.L. Koch, 1847, = N. sanguineus C.L. Koch, 1847, = B. affinis Sseliwanoff, 1879,
      = B. meinerti Sseliwanoff, 1879], Clinopodes C.L. Koch, 1847 [= Poabius C.L.
      Koch, 1847], Clinopodes carinthiacus (Latzel, 1880) [= Geophilus flavidus
      styriacus Attems, 1895, = G. trebevicensis poschiavensis Verhoeff, 1934], C.
      flavidus C.L. Koch, 1847 [= Geophilus flavidus pachypus Verhoeff, 1942, = G.
      flavidus faitanus Verhoeff, 1943, = G. flavidus improvisus Verhoeff, 1943, = G.
      flavidus karamani Verhoeff, 1943, = G. flavidus sorattinus Verhoeff, 1951],
      Dignathodon Meinert, 1870 [= Rhysonotum Attems, 1952], Escaryus retusidens
      Attems, 1904 [= E. retusidens pallidus Folkmanova, 1956], Geophilus Leach, 1814
      [= Homalarthrus Agassiz, 1846, = Esthiomenus Gistel, 1847, = Geophilus
      (Anadenophilus) Verhoeff, 1928], Geophilus aetnensis Verhoeff, 1928 [= G.
      insculptus debilis Brolemann, 1930, = G. evisensis Verhoeff, 1943, = G. henroti
      Manfredi, 1956, = G. aetnensis pollinensis Manfredi, 1957], G. alpinus Meinert,
      1870 [= G. impressus C.L. Koch, 1847, = G. palustris C.L. Koch, 1863, = G.
      insculptus tauerorum Verhoeff, 1928, = G. glacialis inermis Verhoeff, 1938, = G.
      glacialis unguiculatus Verhoeff, 1938, = G. proximus rhenanus Verhoeff, 1895, =
      G. anglicanus Bagnall, 1935, = G. langkofelanus Verhoeff, 1938], G. bobolianus
      Verhoeff, 1928 [= G. longicornis aternanus Verhoeff, 1934], G. carpophagus Leach,
      1815 [= Arthronomalus similis Newport, 1845, = G. pachymeropus Eisen & Stuxberg,
      1868, = G. luridus Meinert, 1870], G. easoni Arthur, Foddai, Kettle, Lewis,
      Luczynski & Minelli 2001 [= Arthronomalus crassicornis Parfitt, 1866], G.
      electricus (Linnaeus, 1758) [= Scolopendra phosphorica Fourcroy, 1785], G. flavus
      (De Geer, 1778) [= G. longicornis trisulcus Silvestri, 1895, = G. longicornis
      glaber Verhoeff, 1928, = G. pygmaeus styricus Verhoeff, 1895, = G. longicornis
      pseudotruncorum Verhoeff, 1896, = G. longicornis styricorum Verhoeff, 1934, = G.
      carnicus praedator Verhoeff, 1937, = Pachymerium flavum Folkmanova, 1949, = G.
      osquidatum  porosus Dobroruka, 1957, = Schizotaenia ornata Folkmanova &
      Dobroruka, 1960], G. fucorum Brolemann, 1909 [= G. longicornis taorminensis
      Verhoeff, 1928, = G. ruinarum Verhoeff, 1931, = Pachymerium dragani Capuse,
      1975], G. gavoyi Chalande, 1910 [= G. gavoyi elongatus Chalande, 1910], G.
      proximus C.L. Koch, 1847 [= G. ganonotus Attems, 1901, = G. eremophilus Lignau,
      1933], G. pygmaeus Latzel, 1880 [= G. cispadanus Silvestri, 1896, = G. carnicus
      Verhoeff, 1928], G. pyrenaicus Chalande, 1909 [= G. pyrenaicus elongatus
      Chalande, 1909], G. seurati Brolemann, 1924 [= G. litorivagus Verhoeff, 1943],
      Gnathoribautia Brolemann, 1909 [= Turkomerium Chamberlin, 1952], Haplophilus
      Cook, 1896 [= Bothrohaplophilus Verhoeff, 1908, = Nesoporogaster Verhoeff, 1924],
      Haplophilus dimidiatus (Meinert, 1870) [= Himantarium gestri Pocock, 1890, = Ital
      ophilus sorattinus Verhoeff, 1951], H. excavatus (Verhoeff, 1924) [=
      Nesoporogaster hispanica Matic & Darabantu, 1969], H. souletinus Brolemann, 1907
      [= H. souletinus lusitanus Verhoeff, 1925], H. subterraneus (Shaw, 1794) [= H.
      subterraneus elongatus Chalande & Ribaut, 1909], H. superbus (Meinert, 1870) [=
      Himantarium filum Meinert, 1870], Haploschendyla Verhoeff, 1900 [= Dalmatodyla
      Verhoeff, 1938, = Aporophilus Attems, 1903], Haploschendyla grantii (Pocock,
      1891) [= Geophilus barbaricus Meinert, 1870, = H. europaea latzeli Demange,
      1959], Henia bicarinata (Meinert, 1870) [= H. bicarinata elongata Brolemann,
      1930, = H. bicarinata lapadensis Verhoeff, 1938], H. illyrica (Meinert, 1870) [=
      Chaetechelyne herzegowinensis Verhoeff, 1938, = H. illyrica absoloni Dobroruka,
      1959], H. montana (Meinert, 1870) [= Chaetechelyne vesuviana pharyngealis
      Verhoeff, 1928], H. valida (Attems, 1927) [= Chaetechelyne osellai Matic &
      Darabantu, 1968], H. vesuviana (Newport, 1845) [= Scolopendra fusca Fourcroy,
      1785, = Chaetechelyne sorattina Verhoeff, 1951], Hydroschendyla submarina (Grube,
      1872) [= Arthronomalus littoralis Parfitt, 1874], Pachymerium coiffaiti Demange,
      1959 [= P. ferrugineum maderianum Demange, 1959], P. ferrugineum (C.L. Koch,
      1835) [= Geophilus caucasicus Attems, 1903, = P. tabacarui Capuse, 1968],
      Schendyla Bergsoe & Meinert, 1866 [= Astenoschendyla Brolemann, 1930, =
      Echinoschendyla Brolemann & Ribaut, 1912, = Microschendyla Brolemann & Ribaut,
      1912, = Schizoschendyla Brolemann & Ribaut, 1912], Schendyla carniolensis
      Verhoeff, 1902 [= Poabius bistriatus C.L. Koch, 1847, = S. nemorensis quarnerana
      Verhoeff, 1937, = S. carniolensis clausensis Verhoeff, 1938, = S. carniolensis
      nivalis Verhoeff, 1938, = S. tesselata Verhoeff, 1943], S. nemorensis (C.L. Koch,
      1837) [= S. nemorensis fountaini Turk, 1944, = Brachygeophilus sinionus Manfredi,
      1953], S. tyrolensis (Meinert, 1870) [= Brachyschendyla montana prominens Ribaut
      & Brolemann, 1927, = S. montana herculis Verhoeff, 1938, = Brachyschendyla
      montana balcanica Kaczmarek, 1969, = Brachyschendyla dobrogica Matic & Darabantu,
      1970], S. vizzavonae Leger & Duboscq, 1903 [= S. pellicensis Verhoeff, 1934, = S.
      incubationum Verhoeff, 1943], S. walachica Verhoeff, 1900 [= S. walachica rhodope
      nsis Kaczmarek, 1969], Stigmatogaster gracilis (Meinert, 1870) [= Himantarium
      laevipes C.L. Koch, 1847, = Geophilus ilicis Fabre, 1855, = S. gracilis robusta
      Attems, 1929, = Diadenoschisma gracile tyrrhenum Verhoeff, 1934, = D. gracile
      quarneranum Verhoeff, 1937, = S. gracilis aeserniana Attems, 1947], Strigamia
      acuminata (Leach, 1815) [ =Scolioplanes acuminatus brevidentatus Verhoeff, 1928,
      = Sc. acuminatus microdon Attems, 1904, = Sc. acuminatus pachypus Verhoeff, 1935,
      = Sc. italicus Verhoeff, 1928], S. crassipes (C.L. Koch, 1835) [= Scolioplanes
      variabilis carniolensis Verhoeff, 1895, = Sc. mediterraneus alsaticus Verhoeff,
      1928, = Sc. mediterraneus carynthiacus Verhoeff, 1928, = Sc. crassipes
      longaronensis Verhoeff, 1935, = Sc. crassipes pegliensis Verhoeff, 1935, = Sc.
      crassipes faitanus Verhoeff, 1943], Thracophilus bulgaricus Verhoeff, 1926 [= T.
      beroni Matic & Darabantu, 1974], T. subterraneus Verhoeff, 1943 [= T. monoporus
      Attems, 1947].We also propose 14 new generic combinations: Dignathodon gracilis
      (Attems, 1952) [from Rhysonotum], Escaryus haasei (Sseliwanoff, 1884) [from
      Geophilus], Geophilus ibericus (Attems, 1952) [from Brachygeophilus], Geophilus
      pauciporus (Machado, 1952) [from Orinophilus], Gnathoribautia syriaca (Attems,
      1903) [from Geophilus], Haplophilus excavatus (Verhoeff, 1924) [from
      Nesoporogaster], Haploschendyla splitensis (Verhoeff, 1938) [from Dalmatodyla],
      Henia duboscqui (Verhoeff, 1943) and H. ruffoi (Matic & Darabantu, 1968) [both
      from Chaetechelyne], Pachymerium minutum (Sseliwanoff, 1884) [from Geophilus],
      Schendyla capusei (Darabantu & Matic, 1969), S. hispanica (Attems, 1952) and S.
      verneri (Folkmanova & Dobroruka, 1960) [all from Brachyschendyla], Tuoba zograffi
      (Brolemann, 1900) [from Geophilus].Lectotypes have been selected for two species:
      Geophilus pusillus Meinert, 1870 and Himantarium mediterraneum Meinert, 1870.In
      seven cases we suggest to conserve currently used names over senior synonyms or
      homonyms: Geophilus alpinus Meinert, 1870 [over G. impressus C.L. Koch, 1847 and
      G. palustris C.L. Koch, 1863], Geophilus easoni Arthur, Foddai, Kettle, Lewis,
      Luczynski & Minelli 2001 [over Arthronomalus crassicornis Parfitt, 1866],
      Gnathoribautia bonensis (Meinert, 1870) [over Necrophloeophagus punctiventris
      Newport, 1844], Bothriogaster signata (Kessler, 1874) [over Notiphilus sanguineus
      C.L. Koch, 1847 and N. taeniatus C.L. Koch, 1847], Schendyla carniolensis
      Verhoeff, 1902 [over Poabius bistriatus C.L. Koch, 1847]. Corresponding
      applications have been submitted to the International Commission on Zoological
      nomenclature for a ruling under the Plenary Powers.  

PMID- 24871281
TI  - Agrotis Ochsenheimer (Lepidoptera, Noctuidae): a systematic analysis of South
      American species.
AB  - The genus Agrotis Ochsenheimer, 1816 (Lepidoptera, Noctuidae) contains about 300
      described species distributed worldwide, excepting the Poles. For South America
      93 species have been described. Different diagnostic characters have been
      proposed for species from the northern Hemisphere, mostly from male genitalia.
      Recently, numerous South American species of the genus have been transferred to
      other genera. In this work, a systematic revision was undertaken of the South
      American species of Agrotis, restricting to 20 the number of species of this
      genus for the region and transferring the other species to different genera
      and/or synonymizing with other species.Based on a detailed study of the external
      morphology and genitalia of both sexes, several nomen clatural changes are
      proposed. New generic synonymy: Mesembreuxoa Hampson = Feltia Walker. New Agrotis
      synonymies include: Scotia forsteri Kohler = A. propriens (Dyar); Agrotis
      peruviana hampsoni Draudt, Rhizagrotis triclava Draudt, and Euxoa andina Kohler =
      A. peruviana (Hampson); Lycophotia achromatica Hampson, Feltia malefida patagiata
      Aurivillius, Prout and Meyrick, Agrotis psammophila Kohler, and Scotia (Feltia)
      canietensis Kohler = A. malefida Guenee; Chorizagrotis benefida Draudt = A.
      experta (Walker); Agrotis livens Kohler and Agrotis capayana Kohler = A.
      araucaria (Hampson). Species transferred to Feltia Walker tent. include: Scotia
      aspersula Kohler, n. comb.; Porosagrotis brachystria Hampson, n. comb.; Agrotis
      carrascoi Kohler, n. comb.; Mesembreuxoa chilensis Hampson, n. comb.; Euxoa
      clavisigna Dognin, n. comb.; Euxoa conifrons Draudt, n. comb.; Agrotis
      consternans Hayes, n. comb.; Euxoa coquimbensis Hampson, n. comb.; Mesembreuxoa
      fasicola Dyar, n. comb.; Chorizagrotis forasmicans Kohler, n. comb.; Agrotis
      giselae Leon, n. comb.; Agrotis gypaetina Guenee, n. comb.; Agrotis hispidula
      Guenee, n. comb.; Euxoa incarum Cockerell, n. comb.; Agrotis india Kohler, n.
      comb.; Scotia mansa Kohler, n. comb.; Scotia picata Kohler, n. comb.; Agrotis
      rondanelli Leon, n. comb.; Euxoa senta Draudt, n. comb.; and Agrotis submontana
      Kohler, n. comb. New Feltia tent. synonymies include: Agrotis daguerrei Kohler,
      Porosagrotis atricentrica Hampson, and Agrotis llanoi Kohler = F. brachystria;
      Lycophotia baeckstroemi Aurivillius = F. deprivata (Walker); Agrotis raveni
      Kohler = F. fasicola; Agrotis gentilii Kohler = F. forasmicans; Scotia nyei
      Kohler, Euxoa australis Kohler, and Scotia liniclinans Kohler = F. hispidula;
      Euxoa bosqui Kohler and Euxoa griseosparsa Kohler = F. lutescens (Blanchard);
      Euxoa praeocupata Kohler, Agrotis andinicola Kohler, and Scotia songoensis Kohler
      = F. subandina (Kohler); Agrotis maldonadoi Kohler = F. submontana. New
      combinations of Agrotis species: Anicla albiorbis (Dyar), n. comb.;
      Noctubourgognea chimaera (Kohler), n. comb.; Noctubourgognea dissociata
      (Staudinger), n. comb.; Pseudoleucania nigrocollaris (Kohler), n. comb.; and P.
      wittmeri (Kohler), n. comb. One lectotype and one paralectotype are designated
      for A. edmondsi Butler. The 20 species of South American Agrotis are redescribed
      using characters of color pattern, external morphology of head and thorax, and
      internal morphology of male (including vesica) and female genitalia. This is the
      first time complete eversions and description of male genitalia (aedeagus and
      vesica) and female genitalia are done for almost all the South American species.
      Images of all described characters and dichotomous keys to identify South
      American species of Agrotis are included.  

PMID- 24871282
TI  - Radiation and decline of endodontid land snails in Makatea, French Polynesia.
AB  - The family Endodontidae Pilsbry, 1895 comprised one of the most diverse groups of
      indigenous land snails of Pacific Islands. However, due to anthropogenic
      degradation of their habitats and predation by or competition with introduced
      species, most members of the family are now extinct or severely endangered. Based
      on limited and sporadic collections, the endodontid fauna of the raised coral
      island of Makatea in the western Tuamotu Archipelago was known to consist of four
      valid species, Mautodontha (Mautodontha) daedalea (Gould, 1846), Kleokyphus
      callimus Solem, 1976, K. hypsus Solem, 1976 and Pseudolibera lillianae Solem,
      1976, the last three of which were endemic. To these, we add 18 new species based
      on a reappraisal of museum collections and analysis of abundant new material
      collected in 2005: M. (M.) domaneschii, M. (M.) virginiae, M. (M.) harperae, M.
      (Garrettoconcha) aurora, M. (G.) occidentalis, M. (G.) temaoensis, M. (G.)
      makateaensis, M. (G.) passosi, M. (G.) spelunca, K. cowiei, P. solemi, P.
      matthieui, P. cookei, P. aubertdelaruei, P. extincta, P. paraminderae, P.
      elieporoii, and P. parva. The recently collected material also revealed new
      information on the morphology, intraspecific variation and distribution of the
      four previously known species, which are here revised and re-described. With 22
      recognized taxa, the radiation of endodontids in Makatea is second in species
      richness only to that of Rapa Iti in the Austral Islands, from where 24
      endodontids have been described. Despite intensive field work in Makatea in 2005,
      only M. (M.) daedalea was found alive. All other Makatean endodontids were
      represented solely by empty and worn shells and are probably extinct.  

PMID- 24871283
TI  - Revision of the family Acidopsidae Stevcic, 2005, and the systematic position of
      Typhlocarcinodes Alcock, 1900, Caecopilumnus Borradaile, 1902, and Raoulia Ng,
      1987, with descriptions of two new genera and five new species (Crustacea:
      Brachyura: Goneplacoidea).
AB  - The family Acidopsidae Stevcic, 2005, is revised; and two subfamilies are
      recognised. The Acidopsinae Stevcic, 2005, is characterised by the coxal male
      opening, a quadrate basal antennal article and vulvae arranged near the median
      longitudinal thoracic sternal groove. Three genera are included in the
      Acidopsinae: Acidops Stimpson, 1871 (with two species), Parapilumnus Kossmann,
      1877 (with two species) and Crinitocinus gen. nov. (monotypic for Pilumnus
      alcocki Borradaile, 1902). The Raouliinae Stevcic, 2005 (= Typhlocarcinodidae
      Stevcic, 2005; Caecopilumnidae Stevcic, 2011), is characterised by its coxo
      sternal male opening, a short basal antennal article which is distinctly wider
      than long and vulvae arranged submedially on thoracic sternite 6. Four genera are
      included in the Raouliinae: Raoulia Ng, 1987 (with five species, three of which
      are described as new), Caecopilumnus Borradaile, 1902 (with three species of
      which one is described as new), Typhlocarcinodes Alcock, 1900 (monotypic) and
      Thecaplax gen. nov. (for one new species).  

PMID- 24871285
TI  - Breaking traditions with reciprocal mentoring.

PMID- 24871286
TI  - Academic partnerships: joining students and clinicians in research.

PMID- 24871287
TI  - Nursing informatics: a specialty on the rise.

PMID- 24871290
TI  - How to positively integrate internationally educated nurses.

PMID- 24871291
TI  - On the right side of cutting-edge education.

PMID- 24871292
TI  - Responding to an active shooter and other threats of violence.

PMID- 24871293
TI  - Resiliency and the nurse leader: the importance of equanimity, optimism, and
      perseverance.

PMID- 24871294
TI  - The 5 rights of a healthy team.

PMID- 24871295
TI  - Leadership q&a.

PMID- 24871297
TI  - Validation of the Gambling Motives Questionnaire in Emerging Adults.
AB  - People engage in gambling behaviour for a variety of different reasons, some of
      which are riskier than others in terms of associations with heavy and problem
      gambling. Stewart and Zack (Addiction 103:1110-1117, 2008) developed a measure
      called the Gambling Motives Questionnaire (GMQ) that assesses levels of three
      distinct gambling motives: enhancement (to increase positive emotions), coping
      (to decrease negative emotions), and social (to increase affiliation). While this
      measure has been validated in a community-recruited sample of middle-aged
      gamblers, the GMQ has yet to be validated in emerging adulthood (ages 18-25
      years)-a developmental period associated with increased risk for heavy and
      problematic gambling. The current project tested the psychometric properties of
      the GMQ in a community sample of emerging adult gamblers using archival data from
      the Manitoba Longitudinal Study of Young Adults. Participants (N = 487; 73.9%
      Caucasian; 52.6% female; mean age 22.23 years) completed the GMQ and
      questionnaire measures of gambling behaviour and problems. Exploratory factor
      analysis revealed that a three-factor model adequately fit the data; however,
      problematic items were identified. A modified 9-item version of the GMQ with the
      problem items removed fit the data well. Both the original 15-item and the 9-item
      versions had acceptable subscale alpha reliabilities (alphas >.78). While all
      three subscales (from both the 9-item and 15-item versions) were positively
      correlated with problem gambling, only enhancement motives emerged as a
      significant independent predictor when the other motives and gambling behaviours
      were entered as simultaneous predictors. These results suggest the GMQ is a valid
      measure for tapping motives in emerging adults, and that high enhancement motives
      are particularly predictive of gambling problems in this developmental period.
      Future intervention efforts might specifically target enhancement motives in
      emerging adults.

PMID- 24871298
TI  - Gambling Attitudes and Beliefs Predict Attentional Bias in Non-problem Gamblers.
AB  - Problem gambling has been identified as a public health concern in Australia, and
      a considerable proportion of regular gamblers may be at risk of developing
      gambling related problems. Attentional bias to salient cues has been observed in
      substance addictions, and to some extent, in problem gamblers. This bias appears
      to be indicative of an increase in sensitisation to salient cues as a result of
      continued reforcement of a related behaviour. To test for an attentional bias to
      gambling-related stimuli in non-problem gamblers, the relationships between
      gambling frequency, gambling attitudes and beliefs (GABS-23), and attentional
      bias were investigated. Participants (N = 38) viewed simultaneous pairs of
      gambling-related and neutral images and performed a dot probe task, during which
      their eye-movements were recorded. This enabled both direct and indirect measures
      of attentional bias to be obtained. Gambling frequency and GABS-23 scores
      predicted both direct and indirect measures of a bias in the maintenance of
      attention to gambling cues. No bias in attentional engagement was found. These
      results suggest that regular gamblers who have not yet developed any related
      problems show signs of sensitisation to gambling cues and may be at risk of
      progressing further towards problem gambling. 

PMID- 24871299
TI  - Jackpot Expiry: An Experimental Investigation of a New EGM Player-Protection
      Feature.
AB  - Given the evidence for the motivating influence of electronic gaming machines
      (EGM) jackpots on intensifying player behaviour (Rockloff and Hing in J Gambl
      Stud 1-7, 2013), there is good reason to explore consumer-protection features.
      Jackpot Expiry is a potential feature of a mandatory pre-commitment system or
      player identification system (e.g., loyalty program) whereby the availability of
      jackpots expires after a fixed interval of play. One hundred and thirty
      volunteers (males = 56, females = 74) played a laptop-simulated EGM with a
      starting $20 real-money stake. In the test condition, players were shown a
      "relevant" message stating that the promised jackpot had expired and could no
      longer be won by the participant (after the 20th trial). In the irrelevant
      message condition a similar pop-up message simply said to push the button to
      continue. Lastly, a control condition had no pop-up message about the jackpot
      expiring. The results showed that betting speeds (one indicator of gambling
      intensity) were significantly slowed by the relevant 'expiry' message. Most
      importantly, all wagers past the 20th trial were programmed as losses. Player
      receiving the 'expiry' message for a cash jackpot quit with significantly more
      money remaining on the machine. Therefore, jackpot expiry was effective in
      limiting player losses, while there was no evidence that jackpot expiry reduced
      self-rated player enjoyment of the simulated EGM experience. 

PMID- 24871301
TI  - Distinct effects of positive and negative music on older adults' auditory target
      identification performances.
AB  - Older adults, compared to younger adults, are more likely to attend to pleasant
      situations and avoid unpleasant ones. Yet, it is unclear whether such a
      phenomenon may be generalized to musical emotions. In this study, we investigated
      whether there is an age-related difference in how musical emotions are
      experienced and how positive and negative music influences attention performances
      in a target identification task. Thirty-one young and twenty-eight older adults
      were presented with 40 musical excerpts conveying happiness, peacefulness,
      sadness, and threat. While listening to music, participants were asked to rate
      their feelings and monitor each excerpt for the occurrence of an auditory target.
      Compared to younger adults, older adults reported experiencing weaker emotional
      activation when listening to threatening music and showed higher level of liking
      for happy music. Correct reaction times (RTs) for target identification were
      longer for threatening than for happy music in older adults but not in younger
      adults. This suggests that older adults benefit from a positive musical context
      and can regulate emotion elicited by negative music by decreasing attention
      towards it (and therefore towards the auditory target). 

PMID- 24871300
TI  - Microsatellite organization in the grasshopper Abracris flavolineata (Orthoptera:
      Acrididae) revealed by FISH mapping: remarkable spreading in the A and B
      chromosomes.
AB  - With the aim of acquiring deeper knowledge about repetitive DNAs chromosomal
      organization in grasshoppers, we used fluorescent in situ hybridization (FISH) to
      map the distribution of 16 microsatellite repeats, including mono-, di-, tri- and
      tetra-nucleotides, in the chromosomes of the species Abracris flavolineata
      (Acrididae), which harbors B chromosome. FISH revealed two main patterns: (i)
      exclusively scattered signals, and (ii) scattered and specific signals, forming
      evident blocks. The enrichment was observed in both euchromatic and
      heterochromatic areas and only the motif (C)30 was absent in heterochromatin. The
      A and B chromosomes were enriched with all the elements that were mapped, being
      observed in the B chromosome more distinctive blocks for (GA)15 and (GAG)10. For
      A complement distinctive blocks were noticed for (A)30, (CA)15, (CG)15, (GA)15,
      (CAC)10, (CAA)10, (CGG)10, (GAA)10, (GAC)10 and (GATA)8. These results revealed
      an intense spreading of microsatellites in the A. flavolineata genome that was
      independent of the A+T or G+C enrichment in the repeats. The data indicate that
      the microsatellites compose the B chromosome and could be involved in the
      evolution of this element in this species, although no specific relationship with
      any A chromosome was observed to discuss about its origin. The systematic
      analysis presented here contributes to the knowledge of repetitive DNA
      chromosomal organization among grasshoppers including the B chromosomes. 

PMID- 24871303
TI  - Comparison of Blood Loss in Laser Lipolysis vs Traditional Liposuction.
AB  - BACKGROUND: Laser-assisted liposuction has been associated with reduced blood
      loss. However, this clinical finding has not been evaluated objectively.
      OBJECTIVES: In this study, the authors objectively estimated the blood loss
      volume associated with laser lipolysis vs traditional liposuction in various
      anatomic regions. METHODS: In this prospective study, 56 patients underwent equal
      amounts of traditional and laser-assisted liposuction at 2 contralateral anatomic
      sites. Blood loss volumes were calculated from the lipoaspirates by measuring
      hemoglobin and red blood cell content. The data were analyzed statistically with
      repeated-measures analysis of variance and the Mann-Whitney U test. RESULTS:
      Laser lipolysis can reduce blood loss by more than 50% compared with traditional
      liposuction. Laser lipolysis resulted in significant reductions in mean blood
      loss volumes in the abdomen, flanks, back, and breast. CONCLUSIONS: The authors
      provide objective evidence that laser lipolysis significantly reduces blood loss
      compared with traditional liposuction. LEVEL OF EVIDENCE: 3.

PMID- 24871302
TI  - An integrated mRNA and microRNA expression signature for glioblastoma multiforme
      prognosis.
AB  - Although patients with Glioblastoma multiforme (GBM) have grave prognosis,
      significant variability in patient outcome is observed. The objective of this
      study is to identify a molecular signature for GBM prognosis. We subjected 355
      mRNA and microRNA expression profiles to elastic net-regulated Cox regression for
      identification of an integrated RNA signature for GBM prognosis. A prognostic
      index (PI) was generated for patient stratification. Survival comparison was
      conducted by Kaplan-Meier method and a general multivariate Cox regression
      procedure was applied to evaluate the independence of the PI. The abilities and
      efficiencies of signatures to predict GBM patient outcome was assessed and
      compared by the area under the curve (AUC) of the receiver-operator
      characteristic (ROC). An integrated RNA prognostic signature consisted by 4
      protective mRNAs, 12 risky mRNAs, and 1 risky microRNA was identified. Decreased
      survival was associated with being in the high-risk group (hazard ratio = 2.864,
      P<0.0001). The prognostic value of the integrated signature was validated in five
      independent GBM expression datasets (n = 201, hazard ratio = 2.453, P<0.0001).
      The PI outperformed the known clinical factors, mRNA-only, and miRNA-only
      prognostic signatures for GBM prognosis (area under the ROC curve for the
      integrated RNA, mRNA-only, and miRNA-only signatures were 0.828, 0.742, and 0.757
      at 3 years of overall survival, respectively, P<0.0001 by permutation test). We
      describe the first, to our knowledge, robust transcriptome-based integrated RNA
      signature that improves the current GBM prognosis based on clinical variables,
      mRNA-only, and miRNA-only signatures. 

PMID- 24871304
TI  - Computer-Aided Analysis of the "Beautiful" Umbilicus.
AB  - BACKGROUND: The position, shape, size, and depth of the umbilicus influence the
      overall aesthetics of the abdomen. Hence, umbilicoplasty is a common adjunct to
      aesthetic and reconstructive surgery of the abdominal wall. Delineation of the
      position and shape of the "beautiful" umbilicus can aid in the planning of
      abdominoplasty and lipoabdominoplasty. OBJECTIVES: The authors aimed to identify
      key parameters of the beautiful umbilicus. METHODS: Previously, the authors
      developed software (the Aesthetic Analyzer) for marking and analyzing parameters
      from images of the nose, breast, and umbilicus. In the present study, the
      Aesthetic Analyzer was utilized to determine parameters of the beautiful
      umbilicus from images of 37 Playboy playmates. The vertical position, horizontal
      position, length, and shape of the umbilicus were assessed. RESULTS: Based on
      these images, the beautiful umbilicus possesses the following properties: a
      vertical ratio of 46:54 (with respect to the xiphoid process and lower limit of
      the vulvar cleft), a midline horizontal position, a length that is 5% of the
      length from the xiphoid process to the lower limit of the vulvar cleft, and an
      oval shape with no hooding (29.8%) or superior hooding (21.6%). CONCLUSIONS:
      Awareness of the ideal position, shape, and size of the umbilicus can be useful
      for achieving successful reconstruction of the umbilicus during abdominoplasty
      and lipoabdominoplasty.

PMID- 24871305
TI  - Bulk metallic glass-like scattering signal in small metallic nanoparticles.
AB  - The atomic structure of Ni-Pd nanoparticles has been studied using atomic pair
      distribution function (PDF) analysis of X-ray total scattering data and with
      transmission electron microscopy (TEM). Larger nanoparticles have PDFs
      corresponding to the bulk face-centered cubic packing. However, the smallest
      nanoparticles have PDFs that strongly resemble those obtained from bulk metallic
      glasses (BMGs). In fact, by simply scaling the distance axis by the mean metallic
      radius, the curves may be collapsed onto each other and onto the PDF from a
      metallic glass sample. In common with a wide range of BMG materials, the
      intermediate range order may be fit with a damped single-frequency sine wave.
      When viewed in high-resolution TEM, these nanoparticles exhibit atomic fringes
      typical of those seen in small metallic clusters with icosahedral or decahedral
      order. These two seemingly contradictory results are reconciled by calculating
      the PDFs of models of icosahedra that would be consistent with the fringes seen
      in TEM. These model PDFs resemble the measured ones when significant atom
      position disorder is introduced, drawing together the two diverse fields of
      metallic nanoparticles and BMGs and supporting the view that BMGs may contain
      significant icosahedral or decahedral order. 

PMID- 24871307
TI  - Dimeric flavonoids from Arrabidaea brachypoda and assessment of their anti
      Trypanosoma cruzi activity.
AB  - The nonpolar fraction of an aqueous ethanol extract of the roots of Arrabidaea
      brachypoda, a Brazilian medicinal plant, demonstrated significant in vitro
      activity against Trypanosoma cruzi, the parasite responsible for Chagas disease.
      Targeted isolation of the active constituents led to the isolation of three new
      dimeric flavonoids (1-3), and their structures were elucidated using UV, NMR, and
      HRMS analysis, as well as by chemical derivatization. The anti-T. cruzi activity
      and cytotoxicity toward mammalian cells were determined for these substances.
      Compound 1 exhibited no activity toward T. cruzi, while flavonoids 2 and 3
      exhibited selective activity against these trypomastigotes. Compounds 2 and 3
      inhibited the parasite invasion process and its intracellular development in host
      cells with similar potencies to benznidazole. In addition, compound 2 reduced the
      blood parasitemia of T. cruzi-infected mice. This study has revealed that these
      two dimeric flavonoids represent potential anti-T. cruzi lead compounds for
      further drug development. 

PMID- 24871308
TI  - Investigating hypophosphataemia.

PMID- 24871309
TI  - All RCGP members should be balloted on assisted dying.

PMID- 24871310
TI  - Frailty related aspects of care are under-recognised in UK medical curriculums.

PMID- 24871311
TI  - Coercing women athletes with high androgen levels into medical interventions.

PMID- 24871312
TI  - Post all press releases online, and give them named authors.

PMID- 24871313
TI  - Responsible reporting of research in the media.

PMID- 24871314
TI  - Terence Stephenson: Leading by example.

PMID- 24871315
TI  - Sex testing in sport can ruin lives.

PMID- 24871316
TI  - Assisted dying is not the same as euthanasia.

PMID- 24871317
TI  - Tobacco control policies in South Asia are not tough enough on smokeless tobacco.

PMID- 24871318
TI  - US cancer center advertisements sell treatments using hope and fear, study finds.

PMID- 24871319
TI  - Deep 16S rRNA pyrosequencing reveals a bacterial community associated with Banana
      Fusarium Wilt disease suppression induced by bio-organic fertilizer application.
AB  - Our previous work demonstrated that application of a bio-organic fertilizer (BIO)
      to a banana mono-culture orchard with serious Fusarium wilt disease effectively
      decreased the number of soil Fusarium sp. and controlled the soil-borne disease.
      Because bacteria are an abundant and diverse group of soil organisms that
      responds to soil health, deep 16 S rRNA pyrosequencing was employed to
      characterize the composition of the bacterial community to investigate how it
      responded to BIO or the application of other common composts and to explore the
      potential correlation between bacterial community, BIO application and Fusarium
      wilt disease suppression. After basal quality control, 137,646 sequences and
      9,388 operational taxonomic units (OTUs) were obtained from the 15 soil samples.
      Proteobacteria, Acidobacteria, Bacteroidetes, Gemmatimonadetes and Actinobacteria
      were the most frequent phyla and comprised up to 75.3% of the total sequences.
      Compared to the other soil samples, BIO-treated soil revealed higher abundances
      of Gemmatimonadetes and Acidobacteria, while Bacteroidetes were found in lower
      abundance. Meanwhile, on genus level, higher abundances compared to other
      treatments were observed for Gemmatimonas and Gp4. Correlation and redundancy
      analysis showed that the abundance of Gemmatimonas and Sphingomonas and the soil
      total nitrogen and ammonium nitrogen content were higher after BIO application,
      and they were all positively correlated with disease suppression. Cumulatively,
      the reduced Fusarium wilt disease incidence that was seen after BIO was applied
      for 1-year might be attributed to the general suppression based on a shift within
      the bacteria soil community, including specific enrichment of Gemmatimonas and
      Sphingomonas. 

PMID- 24871320
TI  - Encoded expansion: an efficient algorithm to discover identical string motifs.
AB  - A major task in computational biology is the discovery of short recurring string
      patterns known as motifs. Most of the schemes to discover motifs are either
      stochastic or combinatorial in nature. Stochastic approaches do not guarantee
      finding the correct motifs, while the combinatorial schemes tend to have an
      exponential time complexity with respect to motif length. To alleviate the cost,
      the combinatorial approach exploits dynamic data structures such as trees or
      graphs. Recently (Karci (2009) Efficient automatic exact motif discovery
      algorithms for biological sequences, Expert Systems with Applications 36:7952
      7963) devised a deterministic algorithm that finds all the identical copies of
      string motifs of all sizes [Formula: see text] in theoretical time complexity of
      [Formula: see text] and a space complexity of [Formula: see text] where [Formula:
      see text] is the length of the input sequence and [Formula: see text] is the
      length of the longest possible string motif. In this paper, we present a
      significant improvement on Karci's original algorithm. The algorithm that we
      propose reports all identical string motifs of sizes [Formula: see text] that
      occur at least [Formula: see text] times. Our algorithm starts with string motifs
      of size 2, and at each iteration it expands the candidate string motifs by one
      symbol throwing out those that occur less than [Formula: see text] times in the
      entire input sequence. We use a simple array and data encoding to achieve
      theoretical worst-case time complexity of [Formula: see text] and a space
      complexity of [Formula: see text] Encoding of the substrings can speed up the
      process of comparison between string motifs. Experimental results on random and
      real biological sequences confirm that our algorithm has indeed a linear time
      complexity and it is more scalable in terms of sequence length than the existing
      algorithms. 

PMID- 24871323
TI  - Development of a bipartite ecdysone-responsive gene switch for the oomycete
      Phytophthora infestans and its use to manipulate transcription during axenic
      culture and plant infection.
AB  - Conditional expression systems have been proven to be useful tools for the
      elucidation of gene function in many taxa. Here, we report the development of the
      first useful inducible promoter system for an oomycete, based on an ecdysone
      receptor (EcR) and the ecdysone analogue methoxyfenozide. In Phytophthora
      infestans, the potato late blight pathogen, a monopartite transactivator
      containing the VP16 activation domain from herpes simplex virus, the GAL4 DNA
      binding domain from yeast and the EcR receptor domain from the spruce budworm
      enabled high levels of expression of a beta-glucuronidase (GUS) reporter gene,
      but unacceptable basal activity in the absence of the methoxyfenozide inducer.
      Greatly improved performance was obtained using a bipartite system in which
      transcription is activated by a heterodimer between a chimera of VP16 and the
      migratory locust retinoid X receptor, and a separate EcR-DNA-binding domain
      chimera. Transformants were obtained that exhibited >100-fold activation of the
      reporter by methoxyfenozide, with low basal levels of expression and induced
      activity approaching that of the strong ham34 promoter. Performance varied
      between transformants, probably as a result of position effects. The addition of
      methoxyfenozide enabled strong induction during hyphal growth, zoosporogenesis
      and colonization of tomato. No significant effects of the inducer or
      transactivators on growth, development or pathogenicity were observed. The
      technology should therefore be a useful addition to the arsenal of methods for
      the study of oomycete plant pathogens. 

PMID- 24871324
TI  - Atypical fatal entry wound to the thigh--a case report.
AB  - Stab wounds encountered in medico-legal practice are caused by sharp or blunt
      pointed weapons such as a kitchen knife, dagger, screwdriver, iron rod, etc.
      Atypical entry wounds may result from elasticity of skin, relative movement of
      the victim or the offending weapon or both. These are often described in the
      literature. We report an unusual incised stab injury of the thigh where a single
      atypical entry wound resulted in injury to the femoral vessels. The precise
      causation of such a peculiar entry wound cannot be explained, though it can be
      considered within the dynamic processes involved between victim, assailant and
      the offending weapon. It is recorded because of its academic curiosity. 

PMID- 24871322
TI  - Dietary gluten and the development of type 1 diabetes.
AB  - Gluten proteins differ from other cereal proteins as they are partly resistant to
      enzymatic processing in the intestine, resulting in a continuous exposure of the
      proteins to the intestinal immune system. In addition to being a disease
      initiating factor in coeliac disease (CD), gluten intake might affect type 1
      diabetes development. Studies in animal models of type 1 diabetes have documented
      that the pathogenesis is influenced by diet. Thus, a gluten-free diet largely
      prevents diabetes in NOD mice while a cereal-based diet promotes diabetes
      development. In infants, amount, timing and mode of introduction have been shown
      to affect the diabetogenic potential of gluten, and some studies now suggest that
      a gluten-free diet may preserve beta cell function. Other studies have not found
      this effect. There is evidence that the intestinal immune system plays a primary
      role in the pathogenesis of type 1 diabetes, as diabetogenic T cells are
      initially primed in the gut, islet-infiltrating T cells express gut-associated
      homing receptors, and mesenteric lymphocytes transfer diabetes from NOD mice to
      NOD/severe combined immunodeficiency (SCID) mice. Thus, gluten may affect
      diabetes development by influencing proportional changes in immune cell
      populations or by modifying the cytokine/chemokine pattern towards an
      inflammatory profile. This supports an important role for gluten intake in the
      pathogenesis of type 1 diabetes and further studies should be initiated to
      clarify whether a gluten-free diet could prevent disease in susceptible
      individuals or be used with newly diagnosed patients to stop disease progression.

PMID- 24871325
TI  - Medico-legal autopsy of 1355 unclaimed dead bodies brought to a tertiary care
      hospital in Delhi, India (2006-2012).
AB  - In India, it is estimated that about 13 million people are homeless. As these
      individuals have no close acquaintances, in the event of death, their bodies
      remain unclaimed. These unclaimed corpses pose a major challenge for the local
      law enforcement agencies in identification and thus become an obstacle in solving
      the cases of missing persons. We sought to review the autopsy characteristics and
      causes of death in the unclaimed/unidentified bodies autopsied at the All India
      Institute of Medical Sciences (AIIMS) from 2006 to 2012. Among the total of
      11,786 cases autopsied during the year 2006 to 2012, 1335 (11%) were unclaimed.
      Most of the cases were males (91%) with a male-to-female ratio of 9:1. Mean age
      of the cohort was 43 years (range, 1-85 years). Natural events were the foremost
      cause of death and were more commonly seen in males. While accidental, suicidal
      and homicidal modes were common in younger age groups; natural manner of death
      predominated in the elderly. Most of the cases were found dead on the roadside.
      This paper also compares with the previous study in the same set-up during the
      time period 2001 to 2005. The authors believe that knowledge about the existing
      healthcare facilities need to be reinforced and their utilisation promoted. 

PMID- 24871321
TI  - Novel genetic susceptibility loci for diabetic end-stage renal disease identified
      through robust naive Bayes classification.
AB  - AIMS/HYPOTHESIS: Diabetic nephropathy is a major diabetic complication, and
      diabetes is the leading cause of end-stage renal disease (ESRD). Family studies
      suggest a hereditary component for diabetic nephropathy. However, only a few
      genes have been associated with diabetic nephropathy or ESRD in diabetic
      patients. Our aim was to detect novel genetic variants associated with diabetic
      nephropathy and ESRD. METHODS: We exploited a novel algorithm, 'Bag of Naive
      Bayes', whose marker selection strategy is complementary to that of conventional
      genome-wide association models based on univariate association tests. The
      analysis was performed on a genome-wide association study of 3,464 patients with
      type 1 diabetes from the Finnish Diabetic Nephropathy (FinnDiane) Study and
      subsequently replicated with 4,263 type 1 diabetes patients from the Steno
      Diabetes Centre, the All Ireland-Warren 3-Genetics of Kidneys in Diabetes UK
      collection (UK-Republic of Ireland) and the Genetics of Kidneys in Diabetes US
      Study (GoKinD US). RESULTS: Five genetic loci (WNT4/ZBTB40-rs12137135, RGMA/MCTP2
      rs17709344, MAPRE1P2-rs1670754, SEMA6D/SLC24A5-rs12917114 and SIK1-rs2838302)
      were associated with ESRD in the FinnDiane study. An association between ESRD and
      rs17709344, tagging the previously identified rs12437854 and located between the
      RGMA and MCTP2 genes, was replicated in independent case-control cohorts.
      rs12917114 near SEMA6D was associated with ESRD in the replication cohorts under
      the genotypic model (p < 0.05), and rs12137135 upstream of WNT4 was associated
      with ESRD in Steno. CONCLUSIONS/INTERPRETATION: This study supports the
      previously identified findings on the RGMA/MCTP2 region and suggests novel
      susceptibility loci for ESRD. This highlights the importance of applying
      complementary statistical methods to detect novel genetic variants in diabetic
      nephropathy and, in general, in complex diseases.

PMID- 24871326
TI  - Comparative epigenetic analyses reveal distinct patterns of oncogenic pathways
      activation in breast cancer subtypes.
AB  - Breast cancer is a highly heterogeneous disease that is characterized by genetic
      and epigenetic aberrations; however, our knowledge of epigenetic alterations of
      breast cancer subtypes remains limited. Here, we portrayed and compared the
      alterations of six types of histone modifications and DNA methylation between two
      breast cancer subtypes, luminal and basal. Widespread subtype-specific epigenetic
      alterations were observed in both subtypes, which preferentially occurred within
      CpG islands (CGIs) and promoter regions. Specifically, aberrant DNA methylation
      was mostly located inside CGIs in luminal subtype, whereas in basal subtype it
      was principally located within CGI shores. Moreover, different types and
      combinatorial patterns of epigenetic alterations were found to occupy at promoter
      regions between these two subtypes. And these epigenetic alterations regulated
      corresponding gene expression in a synergetic way in both subtypes. Functional
      enrichment analysis highlighted that epigenetically dysregulated genes were
      significantly involved in the hallmarks of cancers, most of which were subtype
      specific. Even genes involved in the same hallmarks associated biological
      processes were affected by various types of epi-modifications in different
      subtypes. Finally, we revealed distinct patterns of oncogenic pathways activation
      in different subtypes and provided novel insights into subtype specific
      therapeutic opportunities. In addition, genes in the key signaling pathways were
      able to discriminate between disease phenotypes, and subtype-specific progression
      associated genes were identified. This study presents the aberrant epigenetic
      patterns of breast cancer subtypes at a genome-wide level, which will be a highly
      valuable resource for investigations at understanding epigenetic regulation of
      breast cancer subtypes. 

PMID- 24871329
TI  - Muskie Lunacy: does the lunar cycle influence angler catch of muskellunge (Esox
      masquinongy)?
AB  - We analyzed angling catch records for 341,959 muskellunge (Esox masquinongy) from
      North America to test for a cyclic lunar influence on the catch. Using periodic
      regression, we showed that the number caught was strongly related to the 29-day
      lunar cycle, and the effect was consistent across most fisheries. More
      muskellunge were caught around the full and new moon than at other times. At
      night, more muskellunge were caught around the full moon than the new moon. The
      predicted maximum relative effect was ~5% overall. Anglers fishing exclusively on
      the peak lunar day would, on average, catch 5% more muskellunge than anglers
      fishing on random days. On some lakes and at night, the maximum relative effect
      was higher. We obtained angler effort data for Wisconsin, Mille Lacs (MN), and
      Lake Vermilion (MN). For Lake Vermilion there was a significant effect of the
      lunar cycle on angler effort. We could therefore not conclude that the lunar
      effect on catch was due to an effect on fish behavior alone. Several factors
      affected the amount of variation explained by the lunar cycle. The lunar effect
      was stronger for larger muskellunge (>102 cm) than for smaller fish, stronger in
      midsummer than in June or October, and stronger for fish caught at high latitudes
      (>48 degrees N) than for fish caught further south. There was no difference in
      the lunar effect between expert and novice muskellunge anglers. We argue that
      this variation is evidence that the effect of the lunar cycle on catch is
      mediated by biological factors and is not due solely to angler effort and
      reflects lunar synchronization in feeding. This effect has been attributed to
      variation among moon phases in lunar illumination, but our results do not support
      that hypothesis for angler-caught muskellunge. 

PMID- 24871330
TI  - Spatial and temporal dynamics of primary and secondary metabolism in Phaseolus
      vulgaris challenged by Pseudomonas syringae.
AB  - Many defense mechanisms contribute to the plant immune system against pathogens,
      involving the regulation of different processes of the primary and secondary
      metabolism. At the same time, pathogens have evolved mechanisms to hijack the
      plant defense in order to establish the infection and proliferate. Localization
      and timing of the host response are essential to understand defense mechanisms
      and resistance to pathogens (Rico et al. 2011). Imaging techniques, such as
      fluorescence imaging and thermography, are a very valuable tool providing spatial
      and temporal information about a series of plant processes. In this study, bean
      plants challenged with two pathovars of Pseudomonas syringae have been
      investigated. Pseudomonas syringae pv. phaseolicola 1448A and P. syringae pv.
      tomato DC3000 elicit a compatible and incompatible interaction in bean,
      respectively. Both types of host-pathogen interaction triggered different changes
      in the activity of photosynthesis and the secondary metabolism. We conclude that
      the combined analysis of leaf temperature, chlorophyll fluorescence and green
      fluorescence emitted by phenolics allows to discriminate compatible from
      incompatible P. syringae-Phaseolus vulgaris interactions in very early times of
      the infection, prior to the development of symptoms. These can constitute disease
      signatures that would allow an early identification of emerging plagues in crops.

PMID- 24871327
TI  - The WWOX gene modulates high-density lipoprotein and lipid metabolism.
AB  - BACKGROUND: Low levels of high-density lipoprotein (HDL) cholesterol constitutes
      a major risk factor for atherosclerosis. Recent studies from our group reported a
      genetic association between the WW domain-containing oxidoreductase (WWOX) gene
      and HDL cholesterol levels. Here, through next-generation resequencing, in vivo
      functional studies and gene microarray analyses, we investigated the role of WWOX
      in HDL and lipid metabolism. METHODS AND RESULTS: Using next-generation
      resequencing of the WWOX region, we first identified 8 variants significantly
      associated and perfectly segregating with the low-HDL trait in 2
      multigenerational French Canadian dyslipidemic families. To understand in vivo
      functions of WWOX, we used liver-specific Wwox(hep-/-) and total Wwox(-/-) mice
      models, where we found decreased ApoA-I and Abca1 levels in hepatic tissues.
      Analyses of lipoprotein profiles in Wwox(-/-), but not Wwox(hep-/-) littermates,
      also showed marked reductions in serum HDL cholesterol concentrations, concordant
      with the low-HDL findings observed in families. We next obtained evidence of a
      sex-specific effect in female Wwox(hep-/-) mice, where microarray analyses
      revealed an increase in plasma triglycerides and altered lipid metabolic
      pathways. We further identified a significant reduction in ApoA-I and Lpl and an
      upregulation in Fas, Angptl4, and Lipg, suggesting that the effects of Wwox
      involve multiple pathways, including cholesterol homeostasis, ApoA-I/ABCA1
      pathway, and fatty acid biosynthesis/triglyceride metabolism. CONCLUSIONS: Our
      data indicate that WWOX disruption alters HDL and lipoprotein metabolism through
      several mechanisms and may account for the low-HDL phenotype observed in families
      expressing the WWOX variants. These findings thus describe a novel gene involved
      in cellular lipid homeostasis, which effects may impact atherosclerotic disease
      development.

PMID- 24871328
TI  - A pan-cancer proteomic perspective on The Cancer Genome Atlas.
AB  - Protein levels and function are poorly predicted by genomic and transcriptomic
      analysis of patient tumours. Therefore, direct study of the functional proteome
      has the potential to provide a wealth of information that complements and extends
      genomic, epigenomic and transcriptomic analysis in The Cancer Genome Atlas (TCGA)
      projects. Here we use reverse-phase protein arrays to analyse 3,467 patient
      samples from 11 TCGA 'Pan-Cancer' diseases, using 181 high-quality antibodies
      that target 128 total proteins and 53 post-translationally modified proteins. The
      resultant proteomic data are integrated with genomic and transcriptomic analyses
      of the same samples to identify commonalities, differences, emergent pathways and
      network biology within and across tumour lineages. In addition, tissue-specific
      signals are reduced computationally to enhance biomarker and target discovery
      spanning multiple tumour lineages. This integrative analysis, with an emphasis on
      pathways and potentially actionable proteins, provides a framework for
      determining the prognostic, predictive and therapeutic relevance of the
      functional proteome. 

PMID- 24871333
TI  - Test-retest reliability of automated whole body and compartmental muscle volume
      measurements on a wide bore 3T MR system.
AB  - PURPOSE: To measure the test-retest reproducibility of an automated system for
      quantifying whole body and compartmental muscle volumes using wide bore 3 T MRI.
      MATERIALS AND METHODS: Thirty volunteers stratified by body mass index underwent
      whole body 3 T MRI, two-point Dixon sequences, on two separate occasions. Water
      fat separation was performed, with automated segmentation of whole body, torso,
      upper and lower leg volumes, and manually segmented lower leg muscle volumes.
      RESULTS: Mean automated total body muscle volume was 19.32 L (SD9.1) and 19.28 L
      (SD9.12) for first and second acquisitions (Intraclass correlation coefficient
      (ICC) = 1.0, 95% level of agreement -0.32-0.2 L). ICC for all automated test
      retest muscle volumes were almost perfect (0.99-1.0) with 95% levels of agreement
      1.8-6.6% of mean volume. Automated muscle volume measurements correlate closely
      with manual quantification (right lower leg: manual 1.68 L (2SD0.6) compared to
      automated 1.64 L (2SD 0.6), left lower leg: manual 1.69 L (2SD 0.64) compared to
      automated 1.63 L (SD0.61), correlation coefficients for automated and manual
      segmentation were 0.94-0.96). CONCLUSION: Fully automated whole body and
      compartmental muscle volume quantification can be achieved rapidly on a 3 T wide
      bore system with very low margins of error, excellent test-retest reliability and
      excellent correlation to manual segmentation in the lower leg. KEY POINTS:
      Sarcopaenia is an important reversible complication of a number of diseases.
      Manual quantification of muscle volume is time-consuming and expensive. Muscles
      can be imaged using in and out of phase MRI. Automated atlas-based segmentation
      can identify muscle groups. Automated muscle volume segmentation is reproducible
      and can replace manual measurements.

PMID- 24871332
TI  - Dual-energy computed tomography for the assessment of early treatment effects of
      regorafenib in a preclinical tumor model: comparison with dynamic contrast
      enhanced CT and conventional contrast-enhanced single-energy CT.
AB  - OBJECTIVES: The potential diagnostic value of dual-energy computed tomography (DE
      CT) compared to dynamic contrast-enhanced CT (DCE-CT) and conventional contrast
      enhanced CT (CE-CT) in the assessment of early regorafenib treatment effects was
      evaluated in a preclinical setting. METHODS: A rat GS9L glioma model was examined
      with contrast-enhanced dynamic DE-CT measurements (80 kV/140 kV) for 4 min before
      and on days 1 and 4 after the start of daily regorafenib or placebo treatment.
      Tumour time-density curves (0-240 s, 80 kV), DE-CT (60 s) derived iodine maps and
      the DCE-CT (0-30 s, 80 kV) based parameters blood flow (BF), blood volume (BV)
      and permeability (PMB) were calculated and compared to conventional CE-CT (60 s,
      80 kV). RESULTS: The regorafenib group showed a marked decrease in the tumour
      time-density curve, a significantly lower iodine concentration and a
      significantly lower PMB on day 1 and 4 compared to baseline, which was not
      observed for the placebo group. CE-CT showed a significant decrease in tumour
      density on day 4 but not on day 1. The DE-CT-derived iodine concentrations
      correlated with PMB and BV but not with BF. CONCLUSIONS: DE-CT allows early
      treatment monitoring, which correlates with DCE-CT. Superior performance was
      observed compared to single-energy CE-CT. KEY POINTS: * Regorafenib treatment
      response was evaluated by CT in a rat tumour model. * Dual-energy contrast
      enhanced CT allows early treatment monitoring of targeted anti-tumour therapies.
      * Dual-energy CT showed higher diagnostic potential than conventional contrast
      enhanced single-energy CT. * Dual-energy CT showed diagnostic potential
      comparable to dynamic contrast-enhanced CT. * Dual-energy CT is a promising
      method for efficient clinical treatment response evaluation.

PMID- 24871334
TI  - Feasibility of high-resolution pituitary MRI at 7.0 tesla.
AB  - OBJECTIVES: Since the pituitary gland measures 3-8 mm, imaging with the highest
      possible spatial resolution is important for the detection of even smaller
      lesions such as those seen in Cushing's disease. In the current feasibility
      study, we tested a multi-sequence MRI protocol to visualize the pituitary gland
      in high resolution at 7.0 Tesla (7.0 T). METHODS: Ten healthy volunteers were
      examined with a 7.0 T pituitary gland protocol. The protocol consisted of a T1
      weighted magnetization-prepared inversion recovery (MPIR) turbo spin-echo (TSE)
      sequence and a T2-weighted TSE sequence. Additionally, this protocol was tested
      in five patients with clinical and biochemical suspicion of a microadenoma.
      RESULTS: The dedicated protocol was successful in visualizing normal pituitary
      anatomy. At 7.0 T compared to 1.5 T, four times as many slices covered the
      pituitary gland in sagittal and coronal direction. In three patients, a lesion
      was diagnosed at 7.0 T, and was confirmed by histopathology to be a microadenoma.
      CONCLUSION: Head-to-head comparisons of 7.0 T with 1.5 T and 3.0 T are needed
      with larger samples of patients and with imaging times feasible for clinical
      settings. However, the current study suggests that high-resolution 7.0 T MRI of
      the pituitary gland may provide new perspectives when used as a second-line
      diagnostic examination in the specific context of Cushing's disease. KEY POINTS:
      * 7.0 T MRI enables ultra-high-resolution imaging of the pituitary gland. * 7.0 T
      MRI is appropriate to visualize normal pituitary gland anatomy. * The pituitary
      protocol consists of a T 1 -MPIR-TSE and a T 2 -TSE sequence. * In four patients,
      a suspected ACTH-producing microadenoma was visualized at 7.0 T. * Histopathology
      confirmed three of four lesions to be ACTH-producing microadenomas.

PMID- 24871335
TI  - Diffusion-weighted MR imaging for differentiating borderline from malignant
      epithelial tumours of the ovary: pathological correlation.
AB  - OBJECTIVES: To investigate diffusion-weighted (DW) magnetic resonance (MR)
      imaging for differentiating borderline from malignant epithelial tumours of the
      ovary. METHODS: This retrospective study included 60 borderline epithelial
      ovarian tumours (BEOTs) in 48 patients and 65 malignant epithelial ovarian
      tumours (MEOTs) in 54 patients. DW imaging as well as conventional MR imaging was
      performed. Signal intensity on DW imaging was assessed and apparent diffusion
      coefficient (ADC) value was measured. The results were correlated with
      histopathology and cell density. RESULTS: The majority of MEOTs showed high
      signal intensity on DW imaging, whereas most BEOTs showed low or moderate signal
      intensity (P = 0.000). The mean ADC value of the solid components in BEOTs (1.562
      +/- 0.346 * 10(-3) mm(2)/s) was significantly higher than in MEOTs (0.841 +/-
      0.209 * 10(-3) mm(2)/s). A threshold value of 1.039 * 10(-3) mm(2)/s permitted
      the distinction with a sensitivity of 97.0%, a specificity of 92.2% and an
      accuracy of 96.4%. There was an inverse correlation between ADC value and cell
      density (r = -0.609; P = 0.0000) which was significantly lower in BEOTs than in
      MEOTs. CONCLUSIONS: DW imaging is useful for differentiating borderline from
      malignant epithelial tumours of the ovary. KEY POINTS: DW MR imaging is useful
      for differentiating BEOTs from MEOTs. Patients with BEOTs are treated differently
      from patients with MEOTs. Conservative fertility-sparing laparoscopic surgery can
      be performed in patients with BEOTs. BEOTs often affect young women of
      childbearing age.

PMID- 24871331
TI  - Speech sound processing deficits and training-induced neural plasticity in rats
      with dyslexia gene knockdown.
AB  - In utero RNAi of the dyslexia-associated gene Kiaa0319 in rats (KIA-) degrades
      cortical responses to speech sounds and increases trial-by-trial variability in
      onset latency. We tested the hypothesis that KIA- rats would be impaired at
      speech sound discrimination. KIA- rats needed twice as much training in quiet
      conditions to perform at control levels and remained impaired at several speech
      tasks. Focused training using truncated speech sounds was able to normalize
      speech discrimination in quiet and background noise conditions. Training also
      normalized trial-by-trial neural variability and temporal phase locking. Cortical
      activity from speech trained KIA- rats was sufficient to accurately discriminate
      between similar consonant sounds. These results provide the first direct evidence
      that assumed reduced expression of the dyslexia-associated gene KIAA0319 can
      cause phoneme processing impairments similar to those seen in dyslexia and that
      intensive behavioral therapy can eliminate these impairments. 

PMID- 24871336
TI  - Optimising the preoperative planning of deep inferior epigastric perforator flaps
      for breast reconstruction.
AB  - OBJECTIVES: Preoperative planning of deep inferior epigastric perforator (DIEP)
      flaps has become increasingly important in radiology services as multidetector CT
      angiography (CTA) has been proven to be the technique of choice. We aim to
      optimise the process, checking the value of the "Navarra criteria," assessing
      radiological and surgical concordance. METHODS: Preoperative CTA was obtained in
      105 DIEP flaps involving 101 women (mean age 49.1 years). A main perforator
      pedicle and an alternative were chosen, applying a modification of the "Navarra
      criteria," assessing the correlation between the main perforator chosen by the
      radiologist and the one that was ultimately used to perform the flap using the
      Kappa index. RESULTS: In 100 of the 105 DIEP flaps (95.2%), the perforator
      pedicles chosen were ultimately used to raise the flap. Four of the perforator
      pedicles that were not used were dismissed due to avoidable errors in the
      radiological approach. Concordance was very high, with a Kappa index of 0.93 (95%
      CI: 0.87-0.99). CT room time was less than 12 minutes, and reading time was 10
      minutes. CONCLUSIONS: The application of the "Navarra criteria" in preoperative
      planning of DIEP flaps improves radiological and surgical concordance as well as
      the reading process. KEY POINTS: DIEP flap is one of the best techniques for
      breast reconstruction. Preoperative planning is essential in DIEP flaps. CTA is
      the best option for the preoperative planning of DIEP flaps. "Navarra criteria"
      allow radiologists to choose the best perforator to form flaps. Modified "Navarra
      criteria" improves radiological and surgical concordance.

PMID- 24871337
TI  - Open pulled straw vitrification and slow freezing of sheep IVF embryos using
      different cryoprotectants.
AB  - The aim of the present study was to evaluate the post-thaw survival and hatching
      rates of sheep blastocysts using different cryoprotectants. In Experiment 1, Day
      6 sheep embryos were cryopreserved by a slow freezing protocol using 10% ethylene
      glycol (EG), 10% dimethyl sulfoxide (DMSO) or a mixture of 5% EG and 5% DMSO.
      Hatching rates were higher in the 10% EG group than in the 10% DMSO or EG + DMSO
      groups (30% vs 18% and 20%, respectively). In Experiment 2, embryos were
      cryopreserved by open pulled straw (OPS) vitrification using either 33% EG, 33%
      DMSO or a mixture of 16.5% EG + 16.5% DMSO. Re-expansion and hatching rates in
      the EG + DMSO group (79.16% and 52.74%, respectively) were higher than those in
      the EG group (64.28% and 30.02%, respectively), whereas the outcomes for the DMSO
      group were the lowest (45.18% and 8.6%, respectively). In Experiment 3, embryos
      were cryopreserved by OPS vitrification using either 40% EG, 40% DMSO or a
      mixture of 20% EG + 20% DMSO. Re-expansion and hatching rates were highest in the
      EG group than in the EG + DMSO and DMSO groups (92.16% vs 76.30% and 55.84% re
      expansion, respectively; and 65.78% vs 45.55% and 14.46% hatching, respectively).
      In conclusion, OPS vitrification was found to be more efficient for
      cryopreservation of in vitro-developed sheep embryos than traditional freezing. 

PMID- 24871338
TI  - First-order chiral to non-chiral transition in the angular dependence of the
      upper critical induction of the Scharnberg-Klemm p-wave pair state.
AB  - We calculate the temperature T and angular (theta, phi) dependencies of the upper
      critical induction Bc2(theta, phi, T) for parallel-spin superconductors with an
      axially symmetric p-wave pairing interaction pinned to the lattice and a dominant
      ellipsoidal Fermi surface (FS). For all FS anisotropies, the chiral Scharnberg
      Klemm (SK) state Bc2(theta, phi, T) exceeds that of the chiral Anderson-Brinkman
      Morel (ABM) state and exhibits a kink at theta = theta*(T, phi), indicative of a
      first-order transition from its chiral, nodal-direction behavior to its non
      chiral, antinodal-direction behavior. Applicabilities to Sr2RuO4, UCoGe and the
      candidate topological superconductor CuxBi2Se3 are discussed.

PMID- 24871339
TI  - A novel formulation of tigecycline has enhanced stability and sustained
      antibacterial and antileukemic activity.
AB  - Tigecycline is a broad-spectrum, first-in-class glycylcycline antibiotic
      currently used to treat complicated skin and intra-abdominal infections, as well
      as community-acquired pneumonia. In addition, we have demonstrated that
      tigecycline also has in vitro and in vivo activity against acute myeloid leukemia
      (AML) due to its ability to inhibit mitochondrial translation. Tigecycline is
      relatively unstable after reconstitution, and this instability may limit the use
      of the drug in ambulatory infusions for the treatment of infection and may
      prevent the development of optimal dosing schedules for the treatment of AML.
      This study sought to identify a formulation that improved the stability of the
      drug after reconstitution and maintained its antimicrobial and antileukemic
      activity. A panel of chemical additives was tested to identify excipients that
      enhanced the stability of tigecycline in solution at room temperature for up to
      one week. We identified a novel formulation containing the oxygen-reducing agents
      ascorbic acid (3 mg/mL) and pyruvate (60 mg/mL), in saline solution, pH 7.0, in
      which tigecycline (1 mg/mL) remained intact when protected from light for at
      least 7 days. This formulation also preserved the drug's antibacterial and
      antileukemic activity in vitro. Moreover, the novel formulation retained
      tigecycline's antileukemic activity in vivo. Thus, we identified and
      characterized a novel formulation for tigecycline that preserves its stability
      and efficacy after reconstitution. 

PMID- 24871340
TI  - Impact of observation on disposition of elderly patients presenting to emergency
      departments with non-specific complaints.
AB  - BACKGROUND: Emergency Departments (EDs) have to cope with an increasing number of
      elderly patients, often presenting with non-specific complaints (NSC), such as
      generalized weakness. Acute morbidity requiring early intervention is present in
      the majority of patients with NSC. Therefore, an early and optimal disposition
      plan is crucial. The objective of this study was to prospectively study the
      disposition process of patients presenting to the ED with NSC. METHODS: For two
      years, all patients presenting with NSC presenting to an urban ED were screened
      and consecutively included. The initial disposition plan was compared to the
      effective transfer after observation. Optimal disposition was defined as a high
      accuracy regarding disposition of patients with acute morbidity to an internal
      medicine ward. RESULTS: The final study population consisted of 669 patients with
      NSC. Admission to internal medicine increased from 297 (44%) planned admissions
      to 388 (58%) effective admissions after observation. Conversely, transfers to
      geriatric community hospitals and discharges decreased from the initially planned
      372 (56%) patients to 281 (42%) effectively transferred and discharged patients.
      The accuracy regarding disposition of patients with acute morbidity increased
      from 53% to 68% after observation. CONCLUSION: Disposition planning in patients
      with NSC improves after observation, if defined by the accuracy regarding
      hospitalization of patients with acute morbidity. Further research should focus
      on risk stratification tools for timely disposition planning in order to reduce
      high admission rates for patients without acute morbidity and high readmission
      rates for discharged patients with non-specific complaints.

PMID- 24871343
TI  - A sequential bioequivalence design with a potential ethical advantage.
AB  - This paper introduces a two-stage approach for evaluation of bioequivalence,
      where, in contrast to the designs of Diane Potvin and co-workers, two stages are
      mandatory regardless of the data obtained at stage 1. The approach is derived
      from Potvin's method C. It is shown that under circumstances with relatively high
      variability and relatively low initial sample size, this method has an advantage
      over Potvin's approaches in terms of sample sizes while controlling type I error
      rates at or below 5% with a minute occasional trade-off in power. Ethically and
      economically, the method may thus be an attractive alternative to the Potvin
      designs. It is also shown that when using the method introduced here, average
      total sample sizes are rather independent of initial sample size. Finally, it is
      shown that when a futility rule in terms of sample size for stage 2 is
      incorporated into this method, i.e., when a second stage can be abolished due to
      sample size considerations, there is often an advantage in terms of power or
      sample size as compared to the previously published methods.

PMID- 24871341
TI  - Simplification of complex physiologically based pharmacokinetic models of
      monoclonal antibodies.
AB  - Monoclonal antibodies (mAbs) exhibit biexponential profiles in plasma that are
      commonly described with a standard two-compartment model with elimination from
      the central compartment. These models adequately describe mAb plasma PK. However,
      these models ignore elimination from the peripheral compartment. This may lead to
      underestimation of the volume of distribution of the peripheral compartment and
      thus over-predicts concentration in the peripheral compartment. We developed a
      simple and physiologically relevant model that incorporates information on
      binding and dissociation rates between mAb and FcRn receptor, mAb uptake,
      reflection, and catabolic degradation. We employed a previously published PBPK
      model and, with assumptions regarding rates of processes controlling mAb
      disposition, reduced the complex PBPK model to a simpler circular model with
      central, peripheral, and lymph compartments specifying elimination from both
      central and peripheral. We successfully applied the model to describe the PK of
      an investigational mAb. Our model presents an improvement over standard two
      compartmental models in predicting whole-body average tissue concentrations while
      adequately describing plasma PK with minimal complexity and physiologically more
      meaningful parameters.

PMID- 24871342
TI  - Many approved drugs have bioactive analogs with different target annotations.
AB  - Close structural relationships between approved drugs and bioactive compounds
      were systematically assessed using matched molecular pairs. For structural
      analogs of drugs, target information was assembled from ChEMBL and compared to
      drug targets reported in DrugBank. For many drugs, multiple analogs were
      identified that were active against different targets. Some of these additional
      targets were closely related to known drug targets while others were not.
      Surprising discrepancies between reported drug targets and targets of close
      structural analogs were often observed. On one hand, the results suggest that
      hypotheses concerning alternative drug targets can often be formulated on the
      basis of close structural relationships to bioactive compounds that are easily
      detectable. It is conceivable that such obvious structure-target relationships
      are frequently not considered (or might be overlooked) when compounds are
      developed with a focus on a primary target and a few related (or undesired) ones.
      On the other hand, our findings also raise questions concerning database content
      and drug repositioning efforts.

PMID- 24871344
TI  - Telemedicine as a tool to provide family conferences and palliative care
      consultations in critically ill patients at rural health care institutions: a
      pilot study.
AB  - BACKGROUND: Many critically ill patients who transfer from rural hospitals to
      tertiary care centers (TCCs) have poor prognoses, and family members are unable
      to discuss patient prognosis and goals of care with TCC providers until after
      transfer. AIM: Our TCC conducted teleconferences prior to transfer to facilitate
      early family discussions. DESIGN/SETTING: We conducted a retrospective review of
      these telemedicine family conferences among critically ill patients requested for
      transfer which occurred from December 2008 to December 2009 at our TCC. Outcomes
      for each patient and detailed descriptions of the conference content were
      obtained. We also assessed limitations and attitudes and satisfaction with this
      intervention among clinicians. RESULTS: During the 12-month period, 12
      telemedicine consultations were performed. Of these patients, 10 (83%) died in
      the 30 days following the request for transfer. After the telemedicine
      consultation, 8 (67%) patients were transferred to our TCC from their respective
      hospitals, while 4 (33%) patients continued care at their regional hospital and
      did not transfer. Of the patients who transferred to TCC, 7 (88% of those
      transferred) returned to their community after a stay at the TCC. CONCLUSION:
      This study demonstrates that palliative care consultations can be provided via
      telemedicine for critically ill patients and that adequate preparation and
      technical expertise are essential. Although this study is limited by the nature
      of the retrospective review, it is evident that more research is needed to
      further assess its applicability, utility, and acceptability.

PMID- 24871345
TI  - The Use of Emergency Medication Kits in Community Palliative Care: An Exploratory
      Survey of Views of Current Practice in Australian Home-Based Palliative Care
      Services.
AB  - Improving symptom management for palliative care patients has obvious benefits
      for patients and advantages for the clinicians, as workload demands and work
      related stress can be reduced when the emergent symptoms of patients are managed
      in a timely manner. The use of emergency medication kits (EMKs) can provide such
      timely symptom relief. The purpose of this study was to conduct a survey of a
      local service to examine views on medication management before and after the
      implementation of an EMK and to conduct a nationwide prevalence survey examining
      the use of EMKs in Australia. Most respondents from community palliative care
      services indicated that EMKs were not being supplied to palliative care patients
      but believed such an intervention could improve patient care. 

PMID- 24871346
TI  - Delivery of twins following heterotopic grafting of frozen-thawed ovarian tissue.

PMID- 24871347
TI  - In vivo assessment of aortic aneurysm wall integrity using elastin-specific
      molecular magnetic resonance imaging.
AB  - BACKGROUND: The incidence of abdominal aortic aneurysms (AAAs) has increased
      during the last decades. However, there is still controversy about the management
      of medium-sized AAAs. Therefore, novel biomarkers, besides aneurysmal diameter,
      are needed to assess aortic wall integrity and risk of rupture. Elastin is the
      key protein for maintaining aortic wall tensile strength and stability. The
      progressive breakdown of structural proteins, in particular, medial elastin, is
      responsible for the inability of the aortic wall to withstand intraluminal
      hemodynamic forces. Here, we evaluate the usefulness of elastin-specific
      molecular MRI for the in vivo characterization of AAAs. METHODS AND RESULTS: To
      induce AAAs, ApoE(-/-) mice were infused with angiotensin-II. An elastin-specific
      magnetic resonance molecular imaging agent (ESMA) was administered after 1, 2, 3,
      and 4 weeks of angiotensin-II infusion to assess elastin composition of the aorta
      (n=8 per group). The high signal provided by ESMA allowed for imaging with high
      spatial resolution, resulting in an accurate assessment of ruptured elastic
      laminae and the compensatory expression of elastic fibers. In vivo contrast-to
      noise ratios and R1-relaxation rates after ESMA administration were in good
      agreement with ex vivo histomorphometry (Elastica van Gieson stain) and
      gadolinium concentrations determined by inductively coupled plasma mass
      spectroscopy. Electron microscopy confirmed colocalization of ESMA with elastic
      fibers. CONCLUSIONS: Changes in elastin content could be readily delineated and
      quantified at different stages of AAAs by elastin-specific molecular magnetic
      resonance imaging. ESMA-MRI offers potential for the noninvasive detection of the
      aortic rupture site prior to dilation of the aorta and the subsequent in vivo
      monitoring of compensatory repair processes during the progression of AAAs.

PMID- 24871348
TI  - The changing face of heroin use in the United States: a retrospective analysis of
      the past 50 years.
AB  - IMPORTANCE: Over the past several years, there have been a number of mainstream
      media reports that the abuse of heroin has migrated from low-income urban areas
      with large minority populations to more affluent suburban and rural areas with
      primarily white populations. OBJECTIVE: To examine the veracity of these
      anecdotal reports and define the relationship between the abuse of prescription
      opioids and the abuse of heroin. DESIGN, SETTING, AND PARTICIPANTS: Using a mixed
      methods approach, we analyzed (1) data from an ongoing study that uses
      structured, self-administered surveys to gather retrospective data on past drug
      use patterns among patients entering substance abuse treatment programs across
      the country who received a primary (DSM-IV) diagnosis of heroin use/dependence (n
      = 2797) and (2) data from unstructured qualitative interviews with a subset of
      patients (n = 54) who completed the structured interview. MAIN OUTCOMES AND
      MEASURES: In addition to data on population demographics and current residential
      location, we used cross-tabulations to assess prevalence rates as a function of
      the decade of the initiation of abuse for (1) first opioid used (prescription
      opioid or heroin), (2) sex, (3) race/ethnicity, and (4) age at first use.
      Respondents indicated in an open-ended format why they chose heroin as their
      primary drug and the interrelationship between their use of heroin and their use
      of prescription opioids. RESULTS: Approximately 85% of treatment-seeking patients
      approached to complete the Survey of Key Informants' Patients Program did so.
      Respondents who began using heroin in the 1960s were predominantly young men
      (82.8%; mean age, 16.5 years) whose first opioid of abuse was heroin (80%).
      However, more recent users were older (mean age, 22.9 years) men and women living
      in less urban areas (75.2%) who were introduced to opioids through prescription
      drugs (75.0%). Whites and nonwhites were equally represented in those initiating
      use prior to the 1980s, but nearly 90% of respondents who began use in the last
      decade were white. Although the "high" produced by heroin was described as a
      significant factor in its selection, it was often used because it was more
      readily accessible and much less expensive than prescription opioids. CONCLUSION
      AND RELEVANCE: Our data show that the demographic composition of heroin users
      entering treatment has shifted over the last 50 years such that heroin use has
      changed from an inner-city, minority-centered problem to one that has a more
      widespread geographical distribution, involving primarily white men and women in
      their late 20s living outside of large urban areas.

PMID- 24871349
TI  - Watermarking techniques used in medical images: a survey.
AB  - The ever-growing numbers of medical digital images and the need to share them
      among specialists and hospitals for better and more accurate diagnosis require
      that patients' privacy be protected. As a result of this, there is a need for
      medical image watermarking (MIW). However, MIW needs to be performed with special
      care for two reasons. Firstly, the watermarking procedure cannot compromise the
      quality of the image. Secondly, confidential patient information embedded within
      the image should be flawlessly retrievable without risk of error after image
      decompressing. Despite extensive research undertaken in this area, there is still
      no method available to fulfill all the requirements of MIW. This paper aims to
      provide a useful survey on watermarking and offer a clear perspective for
      interested researchers by analyzing the strengths and weaknesses of different
      existing methods. 

PMID- 24871350
TI  - Biologically inspired scene context for object detection using a single instance.
AB  - This paper presents a novel object detection method using a single instance from
      the object category. Our method uses biologically inspired global scene context
      criteria to check whether every individual location of the image can be naturally
      replaced by the query instance, which indicates whether there is a similar object
      at this location. Different from the traditional detection methods that only look
      at individual locations for the desired objects, our method evaluates the
      consistency of the entire scene. It is therefore robust to large intra-class
      variations, occlusions, a minor variety of poses, low-revolution conditions,
      background clutter etc., and there is no off-line training. The experimental
      results on four datasets and two video sequences clearly show the superior
      robustness of the proposed method, suggesting that global scene context is
      important for visual detection/localization. 

PMID- 24871351
TI  - Isomorphic Ti substitution into SBA-15 without Ti loss and with lower TiO2
      segregation.
AB  - A convenient method has been discovered to incorporate Ti atoms isomorphically
      into a SBA-15 lattice without Ti loss. By hydrolysis of a Ti precursor near
      neutral pH instead of conventional acidic conditions, Ti loss was almost
      eliminated and its segregation to form TiO2 particles was suppressed while the
      mesoporous structure remained intact. 

PMID- 24871353
TI  - Intravenous iron and vertical HIV transmission: any connection?

PMID- 24871354
TI  - Petasin activates AMP-activated protein kinase and modulates glucose metabolism.
AB  - Petasin (1), a natural product found in plants of the genus Petasites, has
      beneficial medicinal effects, such as antimigraine and antiallergy activities.
      However, whether or not 1 modulates metabolic diseases is unknown. In this study,
      the effects of 1 on AMP-activated protein kinase (AMPK), which is considered a
      pharmacological target for treating metabolic diseases, are described. It was
      found that an extract of Petasites japonicus produces an increase in the
      phosphorylation of AMPK in vitro, and the main active compound 1 was isolated.
      When this compound was administered orally to mice, activation of AMPK in the
      liver, skeletal muscle, and adipose tissue was observed. Moreover, pretreatment
      with 1 enhanced glucose tolerance following the administration of a glucose
      solution to normal mice. The mechanism by which 1 activates AMPK was subsequently
      investigated, and an increased intracellular AMP/ATP ratio in the cultured cells
      treated with 1 occurred. In addition, treatment with petasin inhibited
      mitochondrial respiratory chain complex I. Taken together, the present results
      indicated that 1 modulates glucose metabolism and activates AMPK through the
      inhibition of mitochondrial respiration. The preclinical data suggested that
      petasin (1) could be useful for the treatment of metabolic diseases in humans. 

PMID- 24871355
TI  - Evolving indications for Descemet's stripping automated endothelial keratoplasty.
AB  - PURPOSE OF REVIEW: Recent advances in the field of endothelial transplantation,
      including increasing acceptance of Descemet's membrane endothelial keratoplasty,
      may alter the indications for Descemet's stripping automated endothelial
      keratoplasty, to a procedure reserved for complex endothelial disorders. RECENT
      FINDINGS: Recent literature demonstrates that Descemet's membrane endothelial
      keratoplasty provides better and faster visual outcomes and decreased immunologic
      rejection compared to Descemet's stripping automated endothelial keratoplasty.
      However, Descemet's membrane endothelial keratoplasty may be more challenging in
      the management of a number of more complex endothelial disorders. While the
      literature on complex Descemet's membrane endothelial keratoplasty is limited,
      the utility of Descemet's stripping automated endothelial keratoplasty has been
      validated in the management of endothelial dysfunction in the setting of a number
      of comorbid conditions including prior penetrating keratoplasty, prior glaucoma
      surgery, iridocorneal endothelial syndrome, aniridia, aphakia, and anterior
      chamber intraocular lenses, among others. SUMMARY: The increasing adoption of
      Descemet's membrane endothelial keratoplast is changing the practice of
      endothelial keratoplasty. However, limitations of the Descemet's membrane
      endothelial keratoplasty procedure have also served to crystallize the essential
      role of Descemet's stripping automated endothelial keratoplasty in many complex
      endothelial keratoplasty scenarios. This article will review indications for
      endothelial keratoplasty, along with the current evidence for Descemet's
      stripping automated endothelial keratoplasty and Descemet's membrane endothelial
      keratoplasty in their management.

PMID- 24871356
TI  - Optimizing outcomes with Descemet's membrane endothelial keratoplasty.
AB  - PURPOSE OF REVIEW: To review recent advances in posterior lamellar keratoplasty
      and to describe strategies that enhance the outcome of Descemet's membrane
      endothelial keratoplasty (DMEK) and should lead to a more widespread use of this
      technique. RECENT FINDINGS: DMEK offers significant advantages over Descemet's
      stripping automated endothelial keratoplasty (DSAEK) such as less immune reaction
      and better visual acuity because of less higher order aberrations. Donor
      selection should exclude donors under 50 years because of tissue elasticity;
      several advanced techniques now allow donor preparation from both cold and organ
      cultured tissue in about 99% minimizing the risk of graft loss. Oversizing the
      area of Descemet's stripping in relationship to graft size enhances graft
      attachment and use of a standardized approach for graft delivery. Air bubble
      driven nontouch unfolding techniques and, possibly, gas tamponade in the anterior
      chamber further enhance graft attachment and reduce surgery-induced endothelial
      cell loss. Graft orientation is made earlier by marking, slit beam and optical
      coherence tomography. Novel understanding of the functional anatomy of Descemet's
      membrane as well as migration of endothelial cells will allow to further refine
      DMEK and improve its outcome. SUMMARY: Although the superiority of DMEK over
      Descemet's stripping automated endothelial keratoplasty in terms of safety and
      functionality had been further elucidated, remarkable progress has been made in
      the recent past regarding tissue preparation, insertion and intraoperative
      manipulation that will foster the more widespread use of DMEK among corneal
      surgeons.

PMID- 24871357
TI  - Evolution of a revolution in keratoplasty.

PMID- 24871358
TI  - Label-free Pb(II) whispering gallery mode sensing using self-assembled
      glutathione-modified gold nanoparticles on an optical microcavity.
AB  - An ultrasensitive assay for the detection of Pb(II) has been developed using
      whispering gallery mode (WGM) sensing. In this technique a photonic microcavity
      was decorated with glutathione (GSH)-modified gold nanoparticles (Au NPs). The
      resonator was functionalized using an aminosilane to promote adhesion of the GSH
      modified NPs creating a highly sensitive sensor specific to Pb(II). Upon
      introduction of Pb(II) solutions via a fluidic cell, Pb(II) ions bind to the GSH
      Au NP complex and induce a shift of the resonant wavelength. Using this detection
      strategy we show that we are able to detect Pb(II) concentrations down to 0.05 nM
      in the presence of alkaline and heavy metal interferences such as Mg(II), Mn(II),
      Ca(II), Ni(II), Cd(II), Cr(II), Fe(II), and Hg(II). The signal was found to be
      proportional to the Pb(II) concentration within the range of 2.40-48.26 nM and
      was found to have an association constant of 2.15 * 10(5) M(-1) s(-1). The
      sensitivity obtained shows unparalleled advantages over currently available
      technology and satisfies the exposure thresholds set out by world organizations
      such as International Agency for Research on Cancer (IARC) and the Environmental
      Protection Agency (EPA). We believe that this sensor has the potential to be made
      portable for applications in environmental monitoring and in-field applications. 

PMID- 24871360
TI  - beta-hCG and prediction of therapeutic success in ectopic pregnancies treated
      with methotrexate, results from a prospective observational study.
AB  - OBJECTIVE: To evaluate the diagnostic accuracy of different beta-human chorionic
      gonadotrophin (beta-hCG) levels measurement, for predicting success of medical
      treatment in cases diagnosed as tubal ectopic pregnancy (TEP). DESIGN: Five-year
      prospective observational study. SETTING: Prenatal Diagnosis Unit, Vall d'Hebron
      University Hospital - Barcelona. PATIENTS: TEP cases fulfilling criteria for
      medical treatment with Methotrexate. INTERVENTIONS: beta-hCG levels were measured
      on d 0, 4 and 7 of treatment. Results were compared by non-parametrical tests. A
      ROC curve was plotted to define cut-off points. Diagnostic accuracy of the
      different measurements was evaluated. MAIN OUTCOME MEASURE: Failure of treatment
      defined as need for surgical treatment or persistence of high beta-HCG levels
      despite treatment. RESULTS: 126 women were diagnosed as TEP, eligible for medical
      treatment. There were no differences in parity, age, previous TEP, or adnexal
      mass size. Success rate was 88%. beta-HCG decreased significantly more, between
      days 0-7 and 4-7, in the successful cases. LR for success prediction was 6.2 and
      7.8 for beta-HCG levels at days 4 and 7 respectively, 4.02 and 2.47 for decrement
      between days 0-7 (25%) and 4-7 (20%), respectively. CONCLUSION: beta-hCG cutoff
      values have a potential for predicting a successful medical treatment of TEP.

PMID- 24871361
TI  - Transfusion-associated graft versus host disease (TAGVHD)--with reference to
      neonatal period.
AB  - Transfusion-associated graft versus host disease [TAGVHD] results from the
      engraftment of transfused immuno-competent cells in blood transfusion recipients,
      whose immune system is unable to reject them. All blood products containing
      viable, immuno-competent T cells have been implicated in TAGVHD. Presence of a
      "one-way HLA match between donor and recipient" is associated with a
      significantly increased risk of TAGVHD. Though sharing of haplotype is the most
      probable explanation, it is far from adequate. Since TAGVHD is not seen in
      patients with AIDS, and an acute GVHD-like syndrome has been noted in some
      identical twins and autologous (self) transplants, some other processes, possibly
      of an "autoimmune" nature are responsible for TAGVHD. Most of the cases have been
      reported from Japan. This clustering in space and time is rather intriguing. We
      offer here alternative hypothesis. Foetal and then neonatal lymphocytes exhibit
      tolerance towards donor cytotoxic T lymphocytes; and consequently very few cases
      of TAGVHD have been reported in neonates than expected. This tolerance is a part
      of altered immunology of pregnancy. We feel that it is possible to use maternal
      blood for transfusion to her newborn baby by following certain protocol and
      procedure and TAGVHD is no barrier. 

PMID- 24871359
TI  - DNA as a powerful tool for morphology control, spatial positioning, and dynamic
      assembly of nanoparticles.
AB  - CONSPECTUS: Several properties of nanomaterials, such as morphologies (e.g.,
      shapes and surface structures) and distance dependent properties (e.g., plasmonic
      and quantum confinement effects), make nanomaterials uniquely qualified as
      potential choices for future applications from catalysis to biomedicine. To
      realize the full potential of these nanomaterials, it is important to demonstrate
      fine control of the morphology of individual nanoparticles, as well as precise
      spatial control of the position, orientation, and distances between multiple
      nanoparticles. In addition, dynamic control of nanomaterial assembly in response
      to multiple stimuli, with minimal or no error, and the reversibility of the
      assemblies are also required. In this Account, we summarize recent progress of
      using DNA as a powerful programmable tool to realize the above goals. First,
      inspired by the discovery of genetic codes in biology, we have discovered DNA
      sequence combinations to control different morphologies of nanoparticles during
      their growth process and have shown that these effects are synergistic or
      competitive, depending on the sequence combination. The DNA, which guides the
      growth of the nanomaterial, is stable and retains its biorecognition ability.
      Second, by taking advantage of different reactivities of phosphorothioate and
      phosphodiester backbone, we have placed phosphorothioate at selective positions
      on different DNA nanostructures including DNA tetrahedrons. Bifunctional linkers
      have been used to conjugate phosphorothioate on one end and bind nanoparticles or
      proteins on the other end. In doing so, precise control of distances between two
      or more nanoparticles or proteins with nanometer resolution can be achieved.
      Furthermore, by developing facile methods to functionalize two hemispheres of
      Janus nanoparticles with two different DNA sequences regioselectively, we have
      demonstrated directional control of nanomaterial assembly, where DNA strands with
      specific hybridization serve as orthogonal linkers. Third, by using functional
      DNA that includes DNAzyme, aptamer, and aptazyme, dynamic control of assemblies
      of gold nanoparticles, quantum dots, carbon nanotubes, and iron oxide
      nanoparticles in response to one or more stimuli cooperatively have been
      achieved, resulting in colorimetric, fluorescent, electrochemical, and magnetic
      resonance signals for a wide range of targets, such as metal ions, small
      molecules, proteins, and intact cells. Fourth, by mimicking biology, we have
      employed DNAzymes as proofreading units to remove errors in nanoparticle assembly
      and further used DNAzyme cascade reactions to modify or repair DNA sequences
      involved in the assembly. Finally, by taking advantage of different affinities of
      biotin and desthiobiotin toward streptavidin, we have demonstrated reversible
      assembly of proteins on DNA origami.

PMID- 24871362
TI  - The effect of placental abruption on the outcome of extremely premature infants.
AB  - OBJECTIVE: To determine the effect of placental abruption on the outcome of
      infants born between 22 and 26 weeks of gestation. METHODS: A retrospective study
      involving 32 cases of placental abruption. Controls were matched to cases
      according to gestational age and birth weight. Medical records were reviewed to
      confirm maternal background and neonatal outcome. We compared characteristics of
      maternal background and neonatal outcome between the two groups. RESULTS: There
      were no significant differences in the incidence of pregnancy-induced
      hypertension, low maternal fibrinogen (<200 mg/dl), premature rupture of
      membrane, intrauterine infection, ischemic changes of the placenta, or funisitis
      between the groups. Non-reassuring fetal heart rate patterns (NRFHRs) during
      intrapartum were frequently seen in the placental abruption group compared to
      controls (75% versus 51%, p = 0.02). However, no differences were found for the
      incidence of low umbilical artery pH (<7.1), cerebral palsy, or neonatal death.
      The incidence of chronic lung disease (CLD, 66% versus 43%, p = 0.04) and
      hemosiderin deposition on the placenta (16% versus 0%, p < 0.01) was higher in
      abruptions compared to controls. CONCLUSION: Placental abruption has a risk for
      the development of NRFHRs and CLD in infants born between 22 and 26 weeks of
      gestation, but shows no effect on neonatal mortality.

PMID- 24871363
TI  - Trends in birth asphyxia, obstetric interventions and perinatal mortality among
      term singletons: a nationwide cohort study.
AB  - OBJECTIVE: The objective of the present study is to investigate trends in birth
      asphyxia and perinatal mortality in the Netherlands over the last decade.
      METHODS: A nationwide cohort study among women with a term singleton pregnancy.
      We assessed trends in birth asphyxia in relation to obstetric interventions for
      fetal distress. Birth asphyxia was defined as a 5-minute Apgar score < 7 (any
      asphyxia) or 5-minute Apgar score < 4 (severe asphyxia). Perinatal mortality was
      defined as mortality during delivery or within 7 days after birth. Multivariable
      analyses were used to adjust for confounding factors. RESULTS: The prevalence of
      birth asphyxia was 0.85% and severe asphyxia 0.16%. Between 1999 and 2010 birth
      asphyxia decreased significantly with approximately 6% (p = 0.03) and severe
      asphyxia with 11% (p = 0.03). There was no significant change in perinatal
      mortality rate (0.98 per 1000 live births). Simultaneously the referral rate from
      primary to secondary care during labor increased from 20% to 24% (p < 0.0001) and
      the intervention rate for fetal distress from 5.9% to 7.7% (p < 0.0001).
      CONCLUSION: In the Netherlands, the risk of birth asphyxia among term singletons
      has slightly decreased over the last decade; without a significant change in
      perinatal mortality.

PMID- 24871364
TI  - Maternal plasma homocysteine levels in intrauterine growth retardation.
AB  - OBJECTIVE: To investigate a possible correlation between maternal plasma
      homocysteine (HC) concentrations and intrauterine growth retardation (IUGR).
      METHODS: The patients were divided into the IUGR group and controls. The IUGR
      group consisted of 40 women and their newborns with birth weight <the 10th
      percentile for gestational age, whereas 45 infants with birth weight >=the 10th
      percentile comprised the control group. Blood samples were obtained from the
      antecubital vein within 24 h after the delivery. RESULTS: No significant
      differences between the population characteristics in the two groups were found.
      There was a statistically significant difference in serum concentrations of HC:
      5.6 +/- 1.9 umol/L in the IUGR group and 4.6 +/- 1.2 umol/L in controls (p =
      0.01). ROC curve analysis demonstrated that pulsatility index (PI), resistance
      index (RI) and HC concentrations were discriminative markers in IUGR group.
      According to Pearson correlation analysis there was a possible association
      between HC concentrations and PI, RI and middle cerebral artery Doppler
      velocimetry (MCA). CONCLUSION: Higher maternal HC concentration and lower birth
      weight were observed in the IUGR group as compared to the control group. We are
      of the opinion that maternal plasma homocysteine concentration may be a
      prognostic marker in intrauterine growth retardation.

PMID- 24871365
TI  - MicroRNA function in the profibrogenic interplay upon chronic liver disease.
AB  - In chronic liver disease leading to fibrosis, hepatic stellate cells (HSC)
      differentiate into myofibroblasts. Myofibroblastic HSC have taken center stage
      during liver fibrogenesis, due to their remarkable synthesis of extracellular
      matrix proteins, their secretion of profibrogenic mediators and their
      contribution to hypertension, due to elevated contractility. MicroRNAs (miRNAs)
      are small, noncoding RNA molecules of 19-24 nucleotides in length. By either RNA
      interference or inhibition of translational initiation and elongation, each miRNA
      is able to inhibit the gene expression of a wide panel of targeted transcripts.
      Recently, it was shown that altered miRNA patterns after chronic liver disease
      highly affect the progression of fibrosis by their potential to target the
      expression of extracellular matrix proteins and the synthesis of mediators of
      profibrogenic pathways. Here, we underline the role of miRNAs in the interplay of
      the profibrogenic cell communication pathways upon myofibroblastic
      differentiation of hepatic stellate cells in the chronically injured liver. 

PMID- 24871366
TI  - Therapeutic effect of bone marrow mesenchymal stem cells on laser-induced retinal
      injury in mice.
AB  - Stem cell therapy has shown encouraging results for neurodegenerative diseases.
      The retina provides a convenient locus to investigate stem cell functions and
      distribution in the nervous system. In the current study, we investigated the
      therapeutic potential of bone marrow mesenchymal stem cells (MSCs) by systemic
      transplantation in a laser-induced retinal injury model. MSCs from C57BL/6 mice
      labeled with green fluorescent protein (GFP) were injected via the tail vein into
      mice after laser photocoagulation. We found that the average diameters of laser
      spots and retinal cell apoptosis were decreased in the MSC-treated group.
      Interestingly, GFP-MSCs did not migrate to the injured retina. Further
      examination revealed that the mRNA expression levels of glial fibrillary acidic
      protein and matrix metalloproteinase-2 were lower in the injured eyes after MSC
      transplantation. Our results suggest that intravenously injected MSCs have the
      ability to inhibit retinal cell apoptosis, reduce the inflammatory response and
      limit the spreading of damage in the laser-injured retina of mice. Systemic MSC
      therapy might play a role in neuroprotection, mainly by regulation of the
      intraocular microenvironment. 

PMID- 24871367
TI  - The transcriptomes of the crucian carp complex (Carassius auratus) provide
      insights into the distinction between unisexual triploids and sexual diploids.
AB  - Both sexual reproduction and unisexual reproduction are adaptive strategies for
      species survival and evolution. Unisexual animals have originated largely by
      hybridization, which tends to elevate their heterozygosity. However, the extent
      of genetic diversity resulting from hybridization and the genomic differences
      that determine the type of reproduction are poorly understood. In Carassius
      auratus, sexual diploids and unisexual triploids coexist. These two forms are
      similar morphologically but differ markedly in their modes of reproduction.
      Investigation of their genomic differences will be useful to study genome
      diversity and the development of reproductive mode. We generated transcriptomes
      for the unisexual and sexual populations. Genes were identified using homology
      searches and an ab initio method. Estimation of the synonymous substitution rate
      in the orthologous pairs indicated that the hybridization of gibel carp occurred
      2.2 million years ago. Microsatellite genotyping in each individual from the
      gibel carp population indicated that most gibel carp genes were not tri-allelic.
      Molecular function and pathway comparisons suggested few gene expansions between
      them, except for the progesterone-mediated oocyte maturation pathway, which is
      enriched in gibel carp. Differential expression analysis identified highly
      expressed genes in gibel carp. The transcriptomes provide information on genetic
      diversity and genomic differences, which should assist future studies in
      functional genomics. 

PMID- 24871368
TI  - Quantitative proteomics to characterize specific histone H2A proteolysis in
      chronic lymphocytic leukemia and the myeloid THP-1 cell line.
AB  - Proteome studies on hematological malignancies contribute to the understanding of
      the disease mechanism and to the identification of new biomarker candidates. With
      the isobaric tag for relative and absolute quantitation (iTRAQ) method we
      analyzed the protein expression between B-cells of healthy people and chronic
      lymphocytic leukemia (CLL) B-cells. CLL is the most common lymphoid cancer of the
      blood and is characterized by a variable clinical course. By comparing samples of
      patients with an aggressive vs. indolent disease, we identified a limited list of
      differentially regulated proteins. The enhanced sensitivity attributed to the
      iTRAQ labels led to the discovery of a previously reported but still not
      clarified proteolytic product of histone H2A (cH2A) which we further investigated
      in light of the suggested functional properties of this modification. In the
      exploratory proteome study the Histone H2A peptide was up-regulated in CLL
      samples but a more specific and sensitive screening of a larger patient cohort
      indicated that cH2A is of myeloid origin. Our subsequent quantitative analysis
      led to a more profound characterization of the clipping in acute monocytic
      leukemia THP-1 cells subjected to induced differentiation. 

PMID- 24871370
TI  - ONSET OF SEXUAL ACTIVITY AMONG ADOLESCENTS IN HIV/AIDS-AFFECTED HOUSEHOLDS IN SUB
      SAHARAN AFRICA.
AB  - This paper examines the effect of orphanhood and HIV status of adults in a
      household on onset of sexual activity among adolescent girls and boys aged 15-17
      years in sub-Saharan Africa. Multilevel logistic regression models were applied
      to pooled Demographic and Health Surveys data from nineteen countries of sub
      Saharan Africa where HIV test data were collected during 2003-2008 from
      nationally representative samples of men and women of reproductive age. The
      results highlight increased vulnerability among adolescent boys and girls living
      in households where an adult is infected with HIV, and adolescent boys who are
      paternal orphans. On average, adolescent boys and girls living in households
      where at least one adult is HIV-positive have about 25% higher odds of having
      initiated sexual activity compared with their counterparts of similar
      characteristics in households where no adult is HIV-positive. Furthermore,
      adolescent boys who are paternal orphans have about 25% higher odds of having
      initiated sexual activity than their non-orphan counterparts of similar
      individual characteristics. Further analysis reveals that household circumstances
      relating to living arrangements and poverty are important pathways through which
      household HIV/AIDS status is linked to adolescent sexual debut. The findings
      underscore the importance of international efforts in the sub-Saharan Africa
      region to address the plight of other children in HIV/AIDS-affected households,
      beyond orphans. 

PMID- 24871371
TI  - Low Levels of 25-Hydroxy Vitamin D are Independently Associated with the Risk of
      Bacterial Infection in Cirrhotic Patients.
AB  - OBJECTIVES: Low levels of vitamin D are associated with a higher mortality in
      cirrhotic patients, but the role of this deficiency is still unknown. The purpose
      of this study was to assess the levels of vitamin D in cirrhotic patients with
      and without bacterial infection. METHODS: 25-hydroxy (25-OH) vitamin D was
      assessed by immunoassay in 88 patients hospitalized in our hepatology unit.
      RESULTS: The causes of cirrhosis were mainly alcohol (70%), hepatitis C (10%), or
      both (9%). Infections (n=38) mainly included bacteriemia (21%), urinary tract
      infections (24%), and spontaneous bacterial peritonitis (29%). A severe
      deficiency in vitamin D (<10 ng/ml) was observed in 56.8% of patients. Infections
      were more frequent in patients with a severe deficiency compared with the others
      (54 vs. 29%, P=0.02). A severe deficiency in vitamin D was a predictive factor of
      infection (odds ratio=5.44 (1.35-21.97), P=0.017) independently of the Child-Pugh
      score (odds ratio=2.09 (1.47-2.97) P=0.00004) and the C-reactive protein level
      (odds ratio=1.03 (1.002-1.052), P=0.03) in a logistic regression also including
      the alanine amino transferase (not significant). By a Cox regression analysis,
      only the presence of an infection was significantly associated with mortality
      (relative risk=3.24 (1.20-8.76), P=0.02) in a model also associating the Child
      Pugh score (not significant) and the presence of a severe deficiency in vitamin D
      (not significant). CONCLUSIONS: Low levels of 25-OH vitamin D were independently
      associated with bacterial infections in cirrhotic patients. The impact of 25-OH
      vitamin D supplementation on the infection rate and death of cirrhotic patients
      should be assessed in randomized trials.

PMID- 24871372
TI  - Temporal changes in prosaposin expression in the rat dentate gyrus after birth.
AB  - Neurogenesis in the hippocampal dentate gyrus occurs constitutively throughout
      postnatal life. Adult neurogenesis includes a multistep process that ends with
      the formation of a postmitotic and functionally integrated new neuron. During
      adult neurogenesis, various markers are expressed, including GFAP, nestin, Pax6,
      polysialic acid-neural cell adhesion molecule (PSA-NCAM), neuronal nuclei (NeuN),
      doublecortin, TUC-4, Tuj-1, and calretinin. Prosaposin is the precursor of
      saposins A-D; it is found in various organs and can be excreted. Strong
      prosaposin expression has been demonstrated in the developing brain including the
      hippocampus, and its neurotrophic activity has been proposed. This study
      investigated changes in prosaposin in the dentate gyrus of young and adult rats
      using double immunohistochemistry with antibodies to prosaposin, PSA-NCAM, and
      NeuN. Prosaposin immunoreactivity was intense in the dentate gyrus at postnatal
      day 3 (P3) and P7, but decreased gradually after P14. In the dentate gyrus at
      P28, immature PSA-NCAM-positive neurons localized exclusively in the subgranular
      zone were prosaposin-negative, whereas mature Neu-N-positive neurons were
      positive for prosaposin. Furthermore, these prosaposin-negative immature neurons
      were saposin B-positive, suggesting that the neurons take up and degrade
      prosaposin. In situ hybridization assays showed that prosaposin in the adult
      dentate gyrus is dominantly the Pro+9 type, a secreted type of prosaposin. These
      results imply that prosaposin secreted from mature neurons stimulates
      proliferation and maturation of immature neurons in the dentate gyrus. 

PMID- 24871373
TI  - Factors related to participation in paid work after organ transplantation:
      perceptions of kidney transplant recipients.
AB  - PURPOSE: Following kidney transplantation, recipients often have difficulty
      returning to meaningful occupations, including paid employment. The purpose of
      the current study was to describe the sociodemographic profile of kidney
      transplant recipients at a major Canadian Transplant Centre and to identify
      factors perceived to affect participation in paid work post-transplant. METHODS:
      Of the 530 kidney recipients who had received a kidney transplant at our facility
      between 2003 and 2008, 144 recipients were randomly selected, and mailed a
      questionnaire. RESULTS: There were 60 returned questionnaires (41.7 % response
      rate). The average age of responders was 49.4 years and the majority were male
      (68.3 %). While the rate of employment decreased significantly (p = 0.00) from
      68.3 % pre- to 38.3 % post-transplant, retirement rates increased significantly
      (p = 0.00) from 8.3 % pre- to 18.3 % post-transplant. The responders, who were
      not working post-transplant, more likely lived alone (p = 0.05), had a lower
      level of education (p = 0.02), and had lower perceived emotional (p = 0.00) and
      physical (p = 0.00) health status compared to those who returned to work post
      transplant. Gender, donor type, age, and post-transplant complications did not
      differ (p > 0.05) between the working and not working groups. Both person- and
      work-related factors impacted on return to paid work post-transplant. Most
      responders (working and not working) reported feeling emotionally and physically
      ready to work after their transplant. Work-related enablers included positive
      employer attitude towards medical history and employer agreement that recipients
      could take time off for medical appointments. Of those returning to work, the
      nature of their jobs changed from heavy physical demands to sedentary work. There
      was a 20.0 % increase in reliance on government disability insurance post
      transplant. Responders recommended the development of a rehabilitation program
      focused on working and consulting with transplant recipients' employers to
      further enable successful reintegration into the workplace after transplantation.
      CONCLUSIONS: The ability to return to paid work after kidney transplant is a
      complex phenomenon, likely impacted by a combination of person- and work-related
      factors, which contributed to how individuals perceived their abilities to attain
      or return to paid work. It is important that in facilitating renal transplant
      recipients to resume valued life occupations such as paid work, the dynamic
      interactions between personals values, perception of one's abilities, skills, job
      requirements and employer characteristics be considered.

PMID- 24871375
TI  - Healing or harming? Healthcare provider interactions with injured workers and
      insurers in workers' compensation systems.
AB  - INTRODUCTION: Healthcare providers (HCPs) are influential in the injured worker's
      recovery process and fulfil many roles in the delivery of health services.
      Interactions between HCPs and insurers can also affect injured workers'
      engagement in rehabilitation and subsequently their recovery and return to work.
      Consideration of the injured workers' perceptions and experiences as consumers of
      medical and compensation services can provide vital information about the
      quality, efficacy and impact of such systems. The aim of this systematic review
      was to identify and synthesize published qualitative research that focused on the
      interactions between injured workers, HCPs and insurers in workers' compensation
      systems in order to identify processes or interactions which impact injured
      worker recovery. METHOD: A search of six electronic databases for literature
      published between 1985 and 2012 revealed 1,006 articles. Screening for relevance
      identified 27 studies which were assessed for quality against set criteria. A
      final 13 articles of medium and high quality were retained for data extraction.
      RESULTS: Findings were synthesized using a meta-ethnographic approach. Injured
      workers reported that HCPs could play both healing and harming roles in their
      recovery. Supportive patient-centred interaction with HCPs is important for
      injured workers. Difficult interactions between HCPs and insurers were
      highlighted in themes of adversarial relations and organisational pressures.
      Insurer and compensation system processes exerted an influence on the therapeutic
      relationship. Recommendations to improve relationships included streamlining
      administrative demands and increasing education and communication between the
      parties. CONCLUSION: Injured workers with long term complex injuries experience
      difficulties with healthcare in the workers' compensation context. Changes in
      insurer administrative demands and compensation processes could increase HCP
      participation and job satisfaction. This in turn may improve injured worker
      recovery. Further research into experiences of distinct healthcare professions
      with workers' compensation systems is warranted.

PMID- 24871377
TI  - Neutral CH and cationic CH donor groups as anion receptors.
AB  - The design and synthesis of anion selective receptors and chemosensors continues
      to attract considerable interest within the supramolecular community. In recent
      years, increasing attention has focused on the use of neutral and cationic CH
      hydrogen bond donors as anion recognition elements. Over the last five years,
      motifs that support CHX (X = anion) hydrogen bonds have been actively used in
      various shape persistent macrocycles, foldamers and "molecular machines". This
      tutorial review highlights recent developments in host-guest chemistry based on
      the use of neutral and cationic CH hydrogen bond donors. Also discussed are
      various structural classifications, including alkyl CH, phenyl CH, triazole-based
      CH, imidazolium (CH)(+) and triazolium (CH)(+) hydrogen bond donor systems. 

PMID- 24871376
TI  - Subphrenic abscess after appendiceal rupture in full-term pregnancy.

PMID- 24871378
TI  - Vascularization of coralline versus synthetic hydroxyapatite orbital implants
      assessed by gadolinium enhanced magnetic resonance imaging.
AB  - PURPOSE: To evaluate the fibrovascular in-growth of coralline and synthetic
      hydroxyapatite orbital implants by reporting the enhancement patterns on
      Gadolinium-Dietilen triamin penta acetic acid (Gad-DTPA) enhanced magnetic
      resonance imaging (MRI). METHODS: The medical records of 26 patients who had
      undergone primary or secondary orbital implantation between April 2008 and
      February 2011 were reviewed. T1 weighted Gad-DTPA MRI was performed between 5 and
      12 months (mean 9.2 +/- 5.9 months) after implantation and graded as follows to
      evaluate the fibrovascular in-growth of the implants; grade 1 (rim enhancement),
      grade 2 (peripheral foci of enhancement, not including the center), grade 3
      (central, non-homogenous enhancement), grade 4 (central, homogenous enhancement)
      and grade 5 (central, intense enhancement).Results were analysed according to
      vascularization patterns on Gad-DTPA MRI. RESULTS: Central vascularization
      patterns (grade 3, 4 or 5) were seen 62.5% of coralline orbital implants and
      46.1% of synthetic orbital implants. Central fibrovascular in-growth of the
      coralline implants were found significantly more than synthetic implants (p <
      0.05). Central vascularization of coralline implants with primary implantation
      was 75% and with secondary implantation was 50%. Synthetic orbital implantation
      with primary surgery demonstrated 66.6% and synthetic orbital implantation with
      secondary surgery demonstrated 26.6% central vascularization pattern. In both
      natural coralline and synthetic implants, primary orbital implantation was
      demonstrated significantly better fibrovascular in-growth than secondary
      implantation (p < 0.05). Two patients with synthetic orbital implants had
      dehiscence that was repaired by using autogenous fascia lata. CONCLUSIONS: In
      both coralline and synthetic orbital implants, central vascular in-growth was
      observed much more with primary orbital implantation. This study indicates that
      coralline HA orbital implants significantly supply more rapid and homogenous
      vascularization than synthetic implants.

PMID- 24871379
TI  - Rhodium-catalyzed intramolecular annulation via C-H activation leading to fused
      tricyclic indole scaffolds.
AB  - The rhodium(III)-catalyzed intramolecular annulation of alkyne-tethered
      acetanilides for the synthesis of fused tricyclic indole scaffolds via C-H
      activation has been developed, which has the potential for the synthesis of many
      indole alkaloids. This reaction proceeds under mild reaction conditions and with
      tolerance to a variety of functional groups.

PMID- 24871369
TI  - Novel aspects of the liver microenvironment in hepatocellular carcinoma
      pathogenesis and development.
AB  - Hepatocellular carcinoma (HCC) is a prevalent primary liver cancer that is
      derived from hepatocytes and is characterised by high mortality rate and poor
      prognosis. While HCC is driven by cumulative changes in the hepatocyte genome, it
      is increasingly recognised that the liver microenvironment plays a pivotal role
      in HCC propensity, progression and treatment response. The microenvironmental
      stimuli that have been recognised as being involved in HCC pathogenesis are
      diverse and include intrahepatic cell subpopulations, such as immune and stellate
      cells, pathogens, such as hepatitis viruses, and non-cellular factors, such as
      abnormal extracellular matrix (ECM) and tissue hypoxia. Recently, a number of
      novel environmental influences have been shown to have an equally dramatic, but
      previously unrecognized, role in HCC progression. Novel aspects, including diet,
      gastrointestinal tract (GIT) microflora and circulating microvesicles, are now
      being recognized as increasingly important in HCC pathogenesis. This review will
      outline aspects of the HCC microenvironment, including the potential role of GIT
      microflora and microvesicles, in providing new insights into tumourigenesis and
      identifying potential novel targets in the treatment of HCC. 

PMID- 24871380
TI  - Effects of root surface debridement using Er:YAG laser versus ultrasonic scaling 
      a SEM study.
AB  - OBJECTIVE: Despite promising results of Er:YAG laser in periodontal debridement,
      to date there is no consensus about the ideal settings for clinical use. This
      experimental clinical trial aimed to determine the effects of debridement using
      Er:YAG laser and to compare with ultrasonic treatment. MATERIALS AND METHODS:
      Sixty-four teeth were divided into two in vivo and in vitro subgroups. Each tooth
      received ultrasonic treatment on one side and Er:YAG laser debridement at either
      60, 100, 160 or 250 mJ pulse(-1) and at 10 Hz on the other side on a random
      basis. All samples were morphologically analyzed afterwards under scanning
      electron microscope for surface changes and dentinal tubules exposure. Treatment
      duration (d) was also recorded. RESULTS: Laser debridement produced an irregular,
      rough and flaky surface free of carbonization or meltdown while ultrasound
      produced a relatively smoother surface. The number of exposed dentinal tubules
      (n) followed an energy-dependent trend. The number of exposed tubules among the
      in vivo laser groups was n 60 mJ = n 100 mJ < n 160 mJ < n 250 mJ (P < 0.001).
      Also 160 and 250 mJ lasers led to significantly more dentinal exposure than
      ultrasound under in vivo condition. Within the in vitro laser groups, dentinal
      tubules exposure was n 60 mJ < n 100 mJ < n 160 mJ < n 250 mJ (P <= 0.0015).
      Furthermore, in vitro laser treatments at 100, 160 and 250 mJ led to
      significantly more dentinal denudation than ultrasound. Treatment duration (d)
      for the in vivo groups was d 60 mJ > d 100 mJ > d Ultrasound = d 160 mJ > d 250
      mJ (P <= 0.046), while for the in vitro groups it was d 60 mJ > d 100 mJ = d
      Ultrasound = d 160 mJ >d 250 mJ (P <= 0.046). CONCLUSIONS: Due to excessive
      treatment duration and surface damage, Er:YAG laser debridement at 60 and 250 mJ
      pulse(-1), respectively, is not appropriate for clinical use. Although laser
      debridement at 100 and 160 mJ pulse(-1) seems more suitable for clinical
      application, compared to ultrasound the former is more time-consuming and the
      latter is more aggressive. Using a feedback device or lower pulse energies are
      recommended when using laser in closed field.

PMID- 24871381
TI  - Case studies continue to illuminate the cognitive neuroscience of memory.
AB  - The current ubiquity of functional neuroimaging studies, and the importance they
      have had in elucidating brain function, obscures the fact that much of what we
      know about brain-behavior relationships derives largely from the study of single-
      and multiple-patient cases. A major goal of the present review is to describe how
      single cases continue to uniquely and critically contribute to cognitive
      neuroscience theory. With several recent examples from the literature, we
      demonstrate that single cases can both challenge accepted dogma and generate
      hypotheses and theories that steer the field in new directions. We discuss recent
      findings from case studies that specify critical functions of the hippocampus in
      episodic memory and recollection, and clarify its role in nonmnemonic abilities.
      Although we focus on the hippocampus, we discuss other regions and the occurrence
      of new associative learning, as well as the involvement of the ventromedial
      prefrontal and parietal cortices in memory encoding and retrieval. We also
      describe ways of dealing with the shortcomings of case studies, and emphasize the
      partnership of patient and neuroimaging methods in constraining neurocognitive
      models of memory. 

PMID- 24871383
TI  - Lipid oxidation induces structural changes in biomimetic membranes.
AB  - Oxidation can intimately influence and structurally compromise the levels of
      biological self-assembly embodied by intracellular and plasma membranes. Lipid
      peroxidation, a natural metabolic outcome of life with oxygen under light, is
      also a salient oxidation reaction in photomedicine treatments. However, the
      effect of peroxidation on the fate of lipid membranes remains elusive. Here we
      use a new photosensitizer that anchors and disperses in the membrane to achieve
      spatial control of the oxidizing species. We find, surprisingly, that the
      integrity of unsaturated unilamellar vesicles is preserved even for fully
      oxidized membranes. Membrane survival allows for the quantification of the
      transformations of the peroxidized bilayers, providing key physical and chemical
      information to understand the effect of lipid oxidation on protein insertion and
      on other mechanisms of cell function. We anticipate that spatially controlled
      oxidation will emerge as a new powerful strategy for tuning and evaluating lipid
      membranes in biomimetic media under oxidative stress. 

PMID- 24871384
TI  - Incidence of gestational diabetes and birth complications in Switzerland:
      screening in 1042 pregnancies.
AB  - To evaluate the incidence of gestational diabetes mellitus (GDM), gestational
      glucose intolerance (GGI), and birth major complications, a population of 1042
      pregnant women was screened after the end of the second trimester with a two-step
      screening method. Patients with a positive 50-g screening test (plasma glucose >=
      7.8 mmol/l at 1 h) underwent a 3-h standard 100-g oral glucose tolerance test.
      Clinical records of patients and newborns were analysed and compared to
      normotolerant patients group. GDM was found in 4.8% and GGI in 2.6% of all
      screened women of this study population. The patient group with GDM significantly
      differed from control, with a higher proportion of Asiatic women (32.0% versus
      2.9%, p = 0.001) and high prevalence of previous GDM (26.0% versus 0.0%, p <
      0.001). Major neonatal complications occurred more frequently in the dysmetabolic
      groups compared to normotolerant group. Macrosomia was not noted in our
      population. Asiatic origin and previous GDM were strongly associated with an
      increased incidence of GDM in multivariate analysis. This study represents the
      first epidemiological evaluation of GDM/GGI in Switzerland, with a two-step
      screening method. Incidence of GDM and GGI as well as birth complications
      resulted significant in our country.

PMID- 24871387
TI  - Surfactant-assisted direct electron transfer between multi-copper oxidases and
      carbon nanotube-based porous electrodes.
AB  - The effects of pre-treatment with surfactants on the electrocatalytic reaction of
      multi-copper oxidases were quantitatively evaluated using a well-structured
      carbon nanotube forest electrode. It was found that both the charge polarity of
      the head group and the aromatics in the tail part of the surfactants affect the
      efficiency of enzymatic electrocatalysis. 

PMID- 24871385
TI  - Influence of domain stability on the properties of human apolipoprotein E3 and E4
      and mouse apolipoprotein E.
AB  - The human apolipoprotein (apo) E4 isoform, which differs from wild-type apoE3 by
      the single amino acid substitution C112R, is associated with elevated risk of
      cardiovascular and Alzheimer's diseases, but the molecular basis for this
      variation between isoforms is not understood. Human apoE is a two-domain protein
      comprising an N-terminal helix bundle and a separately folded C-terminal region.
      Here, we examine the concept that the ability of the protein to bind to lipid
      surfaces is influenced by the stability (or readiness to unfold) of these
      domains. The lipid-free structures and abilities to bind to lipid and lipoprotein
      particles of a series of human and mouse apoE variants with varying domain
      stabilities and domain-domain interactions are compared. As assessed by urea
      denaturation, the two domains are more unstable in apoE4 than in apoE3. To
      distinguish the contributions of the destabilization of each domain to the
      greater lipid-binding ability of apoE4, the properties of the apoE4 R61T and
      E255A variants, which have the same helix bundle stabilities but altered C
      terminal domain stabilities, are compared. In these cases, the effects on lipid
      binding properties are relatively minor, indicating that the destabilization of
      the helix bundle domain is primarily responsible for the enhanced lipid-binding
      ability of apoE4. Unlike human apoE, mouse apoE behaves essentially as a single
      domain, and its lipid-binding characteristics are more similar to those of apoE4.
      Together, the results show that the overall stability of the entire apoE molecule
      exerts a major influence on its lipid- and lipoprotein-binding properties.

PMID- 24871388
TI  - [Peliosis hepatis: a rare differential diagnosis of focal liver lesions].

PMID- 24871389
TI  - [A 1st evaluation by the Ultrasound Professional Society, AGUS - ultrasound
      update radiology].

PMID- 24871390
TI  - [Judgment of the Federal Social Court - revision dismissed!].

PMID- 24871392
TI  - [New EU guideline - "These are not huge numbers"].

PMID- 24871393
TI  - [The Academy for graduate and continuing education in radiology in April
      implemented a new evaluation system... and why evaluation is so important!].

PMID- 24871394
TI  - [Fundraising for the birthplace of Wilhelm Conrad Rontgen].

PMID- 24871395
TI  - [Interview with genealogists, textile merchants, parish councils and Latin
      students - what is known about the Rontgens today].

PMID- 24871396
TI  - [Society of Southwest Germany Radiologists and Nuclear Medicine Specialists met
      on the 7th and 8th February 2014 in the Karlsruhe Congress Center].

PMID- 24871397
TI  - [Consensus meeting of course directors in breast imaging, 4 May 2013, in
      Frankfurt am Main - Topic: Standards in technique and reporting].

PMID- 24871398
TI  - [Competition restrictions in medical partnership contracts - requirements and
      limitations].

PMID- 24871400
TI  - Reported and predicted structures of Ba(Co,Nb)(1-delta)O3 hexagonal perovskite
      phases.
AB  - The Extended Module Materials Assembly computational method for structure
      solution and prediction has been implemented for close-packed lattices. Exploring
      the family of B-site deficient materials in hexagonal perovskite barium cobalt
      niobates, it is found that the EMMA procedure returns the experimental structures
      as the most stable for the known compositions of Ba3CoNb2O9, Ba5Nb4O15 and
      Ba8CoNb6O24. The unknown compositions Ba11Co2Nb8O33 and Ba13CoNb10O39, having
      longer stacking sequences, are predicted to form as intergrowths of Ba3CoNb2O9
      and Ba5Nb4O15, and are found to have similar stability to pure Ba3CoNb2O9 and
      Ba5Nb4O15, indicating that it is likely they can be synthesised. 

PMID- 24871399
TI  - Mechanism of myo-inositol hexakisphosphate sorption on amorphous aluminum
      hydroxide: spectroscopic evidence for rapid surface precipitation.
AB  - Inositol hexakisphosphates are the most abundant organic phosphates (OPs) in most
      soils and sediments. Adsorption, desorption, and precipitation reactions at
      environmental interfaces govern the reactivity, speciation, mobility, and
      bioavailability of inositol hexakisphosphates in terrestrial and aquatic
      environments. However, surface complexation and precipitation reactions of
      inositol hexakisphosphates on soil minerals have not been well understood. Here
      we investigate the surface complexation-precipitation process and mechanism of
      myo-inositol hexakisphosphate (IHP, phytate) on amorphous aluminum hydroxide
      (AAH) using macroscopic sorption experiments and multiple spectroscopic tools.
      The AAH (16.01 MUmol m(-2)) exhibits much higher sorption density than boehmite
      (0.73 MUmol m(-2)) and alpha-Al2O3 (1.13 MUmol m(-2)). Kinetics of IHP sorption
      and accompanying OH(-) release, as well as zeta potential measurements, indicate
      that IHP is initially adsorbed on AAH through inner-sphere complexation via
      ligand exchange, followed by AAH dissolution and ternary complex formation; last,
      the ternary complexes rapidly transform to surface precipitates and bulk phase
      analogous to aluminum phytate (Al-IHP). The pH level, reaction time, and initial
      IHP loading evidently affect the interaction of IHP on AAH. In situ ATR-FTIR and
      solid-state NMR spectra further demonstrate that IHP sorbs on AAH and transforms
      to surface precipitates analogous to Al-IHP, consistent with the results of XRD
      analysis. This study indicates that active metal oxides such as AAH strongly
      mediate the speciation and behavior of IHP via rapid surface complexation
      precipitation reactions, thus controlling the mobility and bioavailability of
      inositol phosphates in the environment. 

PMID- 24871401
TI  - Appendicitis secondary to metastatic melanoma: review of the National Institutes
      of Health experience.
AB  - IMPORTANCE: Malignant melanoma has an unusual propensity to metastasize to the
      small bowel; however, malignant melanoma with metastatic spread to the appendix
      presenting as acute appendicitis has rarely been reported. We describe cases of
      melanoma of the appendix presenting with appendicitis and review our
      institutional experience with this entity. OBSERVATIONS: Medical records were
      reviewed in patients with melanoma at the National Cancer Institute between
      January 1, 1953, and December 31, 2010, who underwent appendectomy. Of 5822 cases
      of melanoma treated at the National Institutes of Health, appendectomies were
      performed on 31 patients, 2 of whom had acute appendicitis secondary to malignant
      obstruction and presented with symptoms of vague abdominal pain. Both patients
      had been heavily pretreated for metastatic melanoma and had multiple sites of
      intraperitoneal and extraperitoneal disease. On exploratory laparotomy, both
      patients showed clinical evidence of acute appendicitis, and an appendectomy was
      performed. Both patients recovered fully from the operation and proceeded to
      further systemic therapy. CONCLUSIONS AND RELEVANCE: Although rare, the diagnosis
      of appendicitis should be considered in patients with melanoma and acute
      abdominal pain. Timely surgical intervention may allow palliation and the ability
      to pursue subsequent systemic treatment.

PMID- 24871402
TI  - The smallest Cyrtoscydmini of Australia: revision of Microscydmus Saulcy &
      Croissandeau and Penicillidmus gen. n.(Coleoptera, Staphylinidae, Scydmaeninae).
AB  - The Australian members of Microscydmus are revised, and a new subgenus
      Scydmomicrus subgen. n. is established to accommodate seven species: M. (Sc.)
      australiensis Franz (type species of Scydmomicrus), M. (Sc.) nasicornis Franz, M.
      (Sc.) capitiseboraci sp. n., M. (Sc.) queenslandicus sp. n., M. (Sc.) styxianus
      sp. n., M. (Sc.) edithensis sp. n., and M. (Sc.) tooloomensis sp. n. A new
      Microscydmus-like genus, Penicillidmus gen. n., is described to include
      Penicillidmus masseyensis sp. n. (type species of Penicillidmus) and P. unicolor
      sp. n. Species of Microscydmus and Penicillidmus are distributed along the
      eastern coast of Australia, from the northern Cape York to northeastern New South
      Wales, and females of an undescribed Microscydmus are recorded from southern New
      South Wales. The revised taxa comprise the smallest Australian Cyrtoscydmini,
      with body lengths of only 0.50-0.65 mm (Microscydmus) and 0.83-0.86 mm
      (Penicillidmus). For comparative purposes, morphological details of the type
      species of Microscydmus, M. nanus, are described, and structures of the new
      subgenus and new genus are illustrated. Variations of character states within
      Microscydmus found among Australian species are discussed. 

PMID- 24871403
TI  - The identity of the Sarawak freshwater crab Parathelphusa oxygona Nobili, 1901,
      with description of a new species, Parathelphusa nobilii, from Western
      Kalimantan, Indonesia, Borneo (Crustacea: Brachyura: Gecarcinucidae).
AB  - The identity of the common lowland freshwater crab in western Sarawak, Borneo,
      East Malaysia, Parathelphusa oxygona Nobili, 1901 (family Gecarcinucidae), is
      clarified. The species is redescribed and figured, and its taxonomy discussed.
      Specimens from western Kalimantan, Borneo, Indonesia, which have been referred to
      P. oxygona are here referred to a new species, Parathelphusa nobilii. The new
      species can be differentiated from congeners by its relatively more swollen
      branchial regions of the carapace, wider and lower external orbital tooth,
      relatively more slender male abdomen and a straight male first gonopod.  

PMID- 24871404
TI  - A new Andean lizard of the genus Potamites (Sauria, Gymnophthalmidae) from Manu
      National Park, southeastern Peru.
AB  - We describe a new lizard of the genus Potamites from elevations of 1000-2100 m in
      the montane forests of the Cordillera de Paucartambo and the upper Kosnipata
      valley, Region of Cusco, Peru. The new species differs from other species of
      Potamites by having scattered keeled scales on dorsum, an undivided frontonasal
      and absence of femoral pores in females. 

PMID- 24871405
TI  - The neotropical species of Xanthopimpla Saussure (Hymenoptera: Ichneumonidae:
      Pimplinae).
AB  - Xanthopimpla Saussure, 1892 is one of the largest and best studied genera of the
      family Ichneumonidae. It is most species rich in the Oriental and Afrotropical
      regions with only a few species occurring in Central and South America. The
      present study reviews the Neotropical species of the genus including descriptions
      of four new species from Amazonia and Northeast South America. We define a new
      species group: the amazonica species-group, to accommodate the following five
      species: X. amazonica Gomez, Saaksjarvi & Veijalainen, X. guianensis Gomez &
      Saaksjarvi sp. n., X. jussilai Veijalainen, Saaksjarvi & Broad, X. pucallpensis
      Gomez & Saaksjarvi sp. n. and X. vidali Gomez sp. n. The aurita species-group,
      which had hitherto been regarded as the only species-group in the Neotropical
      region, is currently represented by five species: X. allpahuaya Gomez &
      Saaksjarvi sp. n., X. aurita Krieger, X. craspedoptera Krieger, X. rhabdomera
      Townes and X. spiloptera Krieger. The Andean species X. peruana Krieger is
      established as an unplaced species outside of the amazonica and aurita species
      groups. A key to Neotropical species-groups and species of Xanthopimpla is
      provided. Xanthopimpla aurita is recorded for the first time from Ecuador and
      Colombia and its extensive distribution is discussed. Xanthopimpla amazonica, X.
      craspedoptera and X. jussilai are recorded for the first time from Brazil; X.
      amazonica is recorded for the first time from French Guiana; X. spiloptera is
      recorded for the first time from French Guiana and Peru, and X. rhabdomera is
      recorded for the first time from Peru.  

PMID- 24871406
TI  - New species of Atropacarus (Hoplophorella), (Acari, Oribatida, Phthiracaridae)
      from the Afrotropical region.
AB  - Four new species of the subgenus Hoplophorella are desccribed and identified from
      the Afrotropical region: Atropacarus (Hoplophorella) curtisetosus sp. nov. from
      Uluguru Mountains of Tanzania, Atropacarus (Hoplophorella) distinctus sp. nov.
      from Ambohitantely Special Reserve of Madagascar, Atropacarus (Hoplophorella)
      othneios sp. nov. from Ranomafana National Park of Masagascar, and Atropacarus
      (Hoplophorella) stenos sp. nov.  from Nguru and Uluguru Mountains of Tanzania. A
      comparison with the most closely related species of the subgenus Hoplophorella is
      also presented.  

PMID- 24871407
TI  - Monoxia obesula Blake, 1939, a species native to the U.S.A. and adventive to
      Sardinia, Italy (Coleoptera: Chrysomelidae: Galerucinae: Galerucini).
AB  - Monoxia obesula Blake, 1939, a species native to North America, is newly found in
      Sardinia, Italy. This discovery constitutes the first report of the species from
      Europe, as well as the first report from outside of the U.S.A. The species is
      redescribed and illustrated, and errors in the original description are
      corrected. Host plants are species of Atriplex and Chenopodium occurring in
      saline habitats. 

PMID- 24871408
TI  - A new species of troglobitic crab of the genus Stygothelphusa Ng, 1989, from
      Sarawak, Malaysia (Crustacea: Decapoda: Brachyura: Gecarcinucidae).
AB  - A new species of cave crab, Stygothelphusa antu new species, is described from
      limestone formations in Temurang, Sarawak, Malaysia. The new species is the most
      highly adapted to a cavericolous lifestyle among the four known species of
      Stygothelphusa, having a pale body pigmentation, reduced eyes and elongated
      pereopods. In contrast, the other three species have normal eyes that almost
      completely fill the orbits. The new species also differs from its congeners by a
      number of carapace, pereopod and gonopod characters. 

PMID- 24871409
TI  - Advertisement and courtship calls of Phyllodytes wuchereri (Peters, 1873) (Anura:
      Hylidae) .

PMID- 24871410
TI  - A survey of Eupithecia Curtis, 1825 (Lepidoptera, Geometridae, Larentiinae) in
      Mongolia with descriptions of two new species.
AB  - The Eupithecia fauna of Mongolia is surveyed in this paper, drawing on previous
      publications and newly collected material. In total 57 species are recorded. Two
      species Eupithecia anikini Mironov & Galsworthy, sp. n. and Eupithecia munguata
      Mironov & Galsworthy, sp. n. are described as new. Twelve species are recorded as
      new for the fauna of Mongolia, E. olgae, E. illaborata, E. bastelbergeri, E.
      pusillata, E. actaeata, E. vicariata, E. saisanaria, E. simpliciata, E. impolita,
      E. assimilata, E. thalictrata and E. exactata. Habitus and genitalia are
      illustrated for new species, and for little known older species where
      illustrations are not available in recent papers. A further 2 previously
      described species are synonymised, E. mongolica Vojnits of E. satyrata Hubner,
      and E. procera Vojnits of E. exactata Staudinger. 

PMID- 24871412
TI  - A new genus and species of felt scale (Hemiptera: Coccoidea: Eriococcidae) from
      New Caledonia.
AB  - A new genus of Eriococcidae, Choneochiton Hodgson, is introduced to take a new
      species, Choneochiton casuarinae     Hodgson, Mille & Cazeres, off Casuarina
      collina (Casuarinaceae) from New Caledonia.  All stages except the pupa and
      prepupa are described and illustrated.  The new species is thought to be endemic
      to New Caledonia. 

PMID- 24871411
TI  - New species of the feather mite genus Protolichus Trouessart, 1884 (Astigmata,
      Pterolichidae) from lories and lorikeets (Aves: Psittaciformes).
AB  - Five new species of the feather mite genus Protolichus Trouessart, 1884
      (Astigmata, Pterolichidae) are described from parrots of the subfamily Loriinae
      (Psittaciformes: Psittacidae): Protolichus ornatus sp. n. from Trichoglossus
      ornatus (Linnaeus, 1758), P. lorinus sp. n. from Lorius lory (Linnaeus, 1758), P.
      placentis sp. n. from Charmosyna placentis (Temminck, 1835), P. pulchellae sp. n.
      from C. pulchella (Gray GR, 1859), and P. rubiginosus sp. n. from T. rubiginosus
      (Bonaparte, 1850). Protolichus ornatus belongs to the brachiatus species group;
      the other new species belong to the crassior species group. 

PMID- 24871413
TI  - A new species of the genus Opisthotropis Gunther, 1872 from northern Laos
      (Squamata: Natricidae).
AB  - Two specimens, a male and a female, of the genus Opisthotropis Gunther, 1872 were
      collected in a karst formation of northern Louangphabang (or Luang Prabang)
      Province, North Laos. These specimens are assigned to the genus Opisthotropis on
      the basis of their morphology, dentition and cephalic scalation. However, they
      differ from all other known species of Opisthotropis by a combination of the
      following characters: (1) 21-19 scale rows on the fore part of the body, (2) 17
      scale rows at midbody, (3) 22/23 maxillary teeth, (4) 177-181 ventrals, (5) 1
      loreal on each side, in contact with internasal, (6) 7 supralabials, 4th entering
      orbit, (7) dorsum dark bronze-brown, with upper part of dorsum darker than
      lateral sides, without bands or crossbars, and (8) chin and throat blackish-brown
      with a sharp, transversal limit with the ventral colour crossing the posterior
      part of the throat. As a consequence, these specimens are here referred to a new
      species, Opisthotropis durandi spec. nov. The new species is compared with other
      species of the genus, especially the most similar species O. spenceri Smith, 1918
      and O. atra Gunther, 1872, the type species of the genus. An updated key to the
      genera Opisthotropis is provided. Opisthotropis durandi spec. nov. represents the
      first confirmed record of a species of Opisthotropis sensu stricto from Laos and
      it is the 108th snake species currently recorded from the Lao People's Democratic
      Republic.

PMID- 24871414
TI  - Two new species of the genus Khorata (Araneae: Pholcidae) from China.
AB  - Two new species of Khorata are described from China: K. ningyuan sp. nov. and K.
      sancai sp. nov. Both species were collected in caves. 

PMID- 24871415
TI  - A new species of the genus Anthaxia Eschscholtz, 1829 from southern Africa
      (Coleoptera: Buprestidae: Anthaxiini).
AB  - Anthaxia (Haplanthaxia) vlasta sp. nov. from the southern part of the Ethiopian
      Region (Malawi, Republic of South Africa, Rwanda, Tanzania, Zimbabwe) is
      described and illustrated. Its isolated position among the Ethiopian species
      groups is briefly discussed. 

PMID- 24871416
TI  - A new species of Admesturius Galiano, 1988 from north Chile (Araneae: Salticidae:
      Amycoida).

PMID- 24871417
TI  - Characters of external morphology used in Anolis taxonomy-definition of terms,
      advice on usage, and illustrated examples.
AB  - With the aim of establishing a reference for taxonomists, I describe and discuss
      characters of external morphology that have been used widely in descriptions of
      Anolis (sensu lato) species. For most characters, images are provided to
      illustrate the terms and definitions. Where appropriate, I give advice on how the
      counts and measurements should be done. 

PMID- 24871418
TI  - Periclimenaeus colemani sp. nov. (Crustacea; Palaemonidae; Pontoniinae) from
      Heron island, Queensland.
AB  - A further new species of Periclimenaeus (Crustacea: Pontoniinae) from Heron
      Island, Queensland, Australia, is described and illustrated. Periclimenaeus
      colemani sp. nov., an ascidian associate, was collected from coral reef spur and
      groove zone and increases to 30 the numbers of Periclimenaeus known from
      Australia and to 17 the number of species known from Heron Island. 

PMID- 24871419
TI  - Two new species of the family Niphatidae van Soest, 1980 from Northeastern Brazil
      (Haplosclerida: Demospongiae: Porifera).
AB  - This paper deals with niphatid sponges from the coast of the Bahia State,
      northeastern coast of the Brazilian shelf (southwestern Atlantic). Two new
      species are described, Amphimedon estelae sp. nov. and Niphates luizae sp. nov. A
      taxonomic study of those samples is given, including description and
      illustrations. Both species were compared with their congeners present in the
      Atlantic Ocean. 

PMID- 24871420
TI  - A new genus and species of edaphic mite (Acari: esostigmata: Eviphididae) from
      Iran.
AB  - The new genus Pedoniphis gen. nov. (Acari: Mesostigmata: Eviphididae) is
      described from soil detritus in Sabalan Mountains, northwest Iran, with P.
      persicus sp. nov. as type species. Among known eviphidid genera, the new genus is
      the most similar to Scamaphis Karg and Scarabacariphis Masan and it can be
      distinguished especially by the dorsal chaetotaxy (setae J2 absent, setae J5
      rudimentary) and the specific form of the peritrematal-dorsal scutal complex
      (peritrematal shields reduced; peritremes well developed, fused to lateral
      margins of dorsal shield). 

PMID- 24871421
TI  - New genus and species of Neotropical robber flies (Diptera, Asilidae, Asilinae).
AB  - A new genus and species of Papaverellus aureocingulatus from Brazil, belonging to
      the asilid subfamily, is described and illustrated. Photographs of the habitus of
      the male and female in lateral view, and male terminalia in ventral view are
      provided. The systematic position of Papaverellus gen. nov. is suggested and will
      be addressed in a future paper. 

PMID- 24871422
TI  - A new species of Symbiopsocus Li (Psocodea: "Psocoptera": Psocidae) from Taiwan,
      China, with a revised checklist and key to species.
AB  - Symbiopsocus yangminus sp. n. is described based on specimens collected from
      Taiwan, China. We provide an updated checklist and comprehensive geographic
      distribution of Symbiopsocus, including species from China described in
      Mecampsis. The genus Symbiopsocus now comprises 20 species from mainland China,
      two species from Taiwan and one species from Japan. Updated keys to males and
      females of species from China are provided. 

PMID- 24871423
TI  - On plant bugs of conifers in Xinjiang (Western China)  (Hemiptera: Heteroptera:
      Miridae).
AB  - In the northern and central part of Xinjiang (Western China) are distributed 14
      species of coniferous plant bugs of these, 10 species are recorded for the first
      time for China. In the Mongolian Altai are 9 species: 6 widely distributed in the
      Palearctic, Deraeocoris annulipes (Herrich-Schaeffer, 1842), Dichrooscytus
      intermedius Reuter, 1885, Pinalitus rubricatus (Fallen, 1807), Atractotomus morio
      J. Sahlberg, 1883, Plagiognathus vitellinus (Scholtz, 1847), Phoenicocoris
      obscurellus (Fallen, 1829), and 3 Siberian Psallus (Pityopsallus) laricinus
      Vinokurov, 1998, P. (P.) laticeps Reuter, 1878, P. (P.) sachaensis Vinokurov,
      1998. In Chinese Tian Shan and Jungar Alatau occur 5 mountain-Central Asian
      species: Dichrooscytus consorbinus Horvath, 1904, D. josifovi Kerzhner, 1997, D.
      kerzhneri Josifov, 1974 and D. pseudosabinae Reuter, 1896, and Compsidolon
      schrenkianum Konstantinov, Vinokurov, 2011. A key for 5 species of the subgenus
      Pithyopsallus Wagn. is given. 

PMID- 24871424
TI  - Urothelial carcinogen resistance driven by stronger Toll-like receptor 2 (TLR2)
      and Uroplakin III (UP III) defense mechanisms: a new model.
AB  - OBJECTIVE: The objective of the study was to illustrate the applicability and
      significance of the novel Lewis urothelial cancer model compared to the classic
      Fisher 344. METHODS: Fischer 344 and Lewis females rats, 7 weeks old, were
      intravesical instilled N-methyl-N-nitrosourea 1.5 mg/kg every other week for a
      total of four doses. After 15 weeks, animals were sacrificed and bladders
      analyzed: histopathology (tumor grade and stage), immunohistochemistry (apoptotic
      and proliferative indices) and blotting (Toll-like receptor 2-TLR2, Uroplakin III
      UP III and C-Myc). Control groups received placebo. RESULTS: There were
      macroscopic neoplastic lesions in 20 % of Lewis strain and 70 % of Fischer 344
      strain. Lewis showed hyperplasia in 50 % of animals, normal bladders in 50 %. All
      Fischer 344 had lesions, 20 % papillary hyperplasia, 30 % dysplasia, 40 %
      neoplasia and 10 % squamous metaplasia. Proliferative and apoptotic indices were
      significantly lower in the Lewis strain (p < 0.01). The TLR2 and UP III protein
      levels were significantly higher in Lewis compared to Fischer 344 strain (70.8
      and 46.5 % vs. 49.5 and 16.9 %, respectively). In contrast, C-Myc protein levels
      were significantly higher in Fischer 344 (22.5 %) compared to Lewis strain (13.7
      %). CONCLUSIONS: The innovative Lewis carcinogen resistance urothelial model
      represents a new strategy for translational research. Preservation of TLR2 and UP
      III defense mechanisms might drive diverse urothelial phenotypes during
      carcinogenesis in differently susceptible individuals.

PMID- 24871425
TI  - Does HistoScanningTM predict positive results in prostate biopsy? A retrospective
      analysis of 1,188 sextants of the prostate.
AB  - PURPOSE: The role of HistoScanningTM (HS) in prostate biopsy is still
      indeterminate. Existing literature is sparse and controversial. To provide more
      evidence according to that important clinical topic, we analyzed institutional
      data from the Martini-Clinic, Prostate Cancer Center, Hamburg. METHODS: Patients
      who received prostate biopsy and who also received HS were included in the study
      cohort. A single examiner, blinded to pathological results, re-analyzed all HS
      data in accordance with sextants of the prostate. Each sextant was considered as
      an individual case. Corresponding results from biopsy and HS were analyzed. The
      area under the receiver-operating characteristic curve (AUC) for the prediction
      of a positive biopsy by HS was calculated. Furthermore, sensitivity, specificity,
      positive predictive value (PPV) and negative predictive value (NPV) were assessed
      according to different HS signal volume cutoffs (>0, >0.2 and >0.5 ml). RESULTS:
      Overall, 198 men were identified and 1,188 sextants were analyzed. The AUC to
      predict positive biopsy results by HS was 0.58. Sensitivity, specificity, PPV and
      NPV for HS to predict positive biopsy results per sextant, depending on different
      HS signal volume cutoffs (>0, >0.2 and >0.5 ml) were 84.1, 27.7, 29.5 and 82.9 %,
      60.9, 50.6, 28.8 and 79.7 %, and 40.1, 73.3, 33.1 and 78.8 %, respectively.
      CONCLUSIONS: Positive HS signals do not accurately predict positive prostate
      biopsy results according to sextant analysis. We cannot recommend a variation of
      well-established random biopsy patterns or reduction of biopsy cores in
      accordance with HS signals at the moment.

PMID- 24871426
TI  - Manipulating cues in involuntary autobiographical memory: verbal cues are more
      effective than pictorial cues.
AB  - In two experiments, pictorial cues were compared with their verbal labels to
      assess their effectiveness in eliciting involuntary autobiographical memories.
      Cues were relatively complex in Experiment 1 (e.g., relaxing on a beach) and
      simple objects in Experiment 2 (e.g., a ball). In both experiments, participants
      went through a vigilance task in which they were presented with frequent
      nontarget and rare target visual stimuli. Pictures or their corresponding verbal
      labels were also displayed on both target and nontarget stimuli, but participants
      were told that these were irrelevant to the task. They were asked to interrupt
      the vigilance task whenever they became aware of task-unrelated mental contents
      and to report them. In both experiments, more involuntary memories were elicited
      in the verbal cue condition, rather than in the pictorial cue condition. This
      result is discussed in relation to previous work that highlighted the greater
      effectiveness of verbal cues in memory tasks. 

PMID- 24871427
TI  - Formation of ceramophilic chitin and biohybrid materials enabled by a genetically
      engineered bifunctional protein.
AB  - A bifunctional protein composed of a highly negatively charged oyster shell
      protein and a chitin-binding domain enabled the formation of biohybrid materials
      through non-covalent surface modification of chitin nanofibres. The results
      demonstrate that specific biomolecular interactions offer a route for the
      formation of biosynthetic materials. 

PMID- 24871428
TI  - Do the factors associated with female HIV infection vary by socioeconomic status
      in Cameroon?
AB  - One of the most consistent findings in social epidemiology is an inverse
      relationship between indicators of SES and most types of illness. However, a
      growing body of research on HIV in sub-Saharan Africa suggests an intriguing
      reversal of this pattern, particularly with respect to HIV among women. In
      Cameroon, specifically, high-SES women have higher rates of HIV infection
      compared with low-SES women. Using data from the 2004 Cameroon DHS, this study
      explored the relationships between SES and HIV and tested a multivariate model
      designed to highlight the distinctive factors associated with increased risk of
      HIV among women in different SES classes. The results revealed that high-SES
      women who reported engaging in riskier sexual behaviour had the highest levels of
      HIV infection. Surprisingly, among this group increased knowledge of HIV, more
      domestic decision-making authority and access to health care did not reduce
      vulnerability. Meanwhile, among low-SES women relative gender inequality was
      significantly related to HIV risk. Specifically, among this group of women,
      having a partner with higher education was strongly associated with greater HIV
      risk. The results suggest that different approaches targeting each sub-group are
      needed to effectively combat the disease.

PMID- 24871431
TI  - Hybrid functionals applied to perovskites.
AB  - After being used for years in the chemistry community to describe molecular
      properties, hybrid functionals have been increasingly and successfully employed
      for a wide range of solid state problems which are not accurately accessible by
      standard density functional theory. In particular, the upsurge of interest in
      transition metal perovskite-based compounds, motivated by their technological
      relevance and functional ductility, has incentivized the use of hybrid
      functionals for realistic applications, as hybrid functionals appear to be
      capable of capturing the complex correlated physics of this class of oxide
      material, characterized by a subtle coupling between several competing
      interactions (lattice, orbital, spin). Here we present a map of recent
      applications of hybrid functionals to perovskites, aiming to cover an ample
      spectra of cases, including the 'classical' 3d compounds (manganites, titanates,
      nickelates, ferrites, etc.), less conventional examples from the the 4d
      (technetiates) and 5d (iridates) series, and the (non-transition metal) sp
      perovskite BaBiO3. We focus our attention on the technical aspects of the hybrid
      functional formalism, such as the role of the mixing and (for range-separated
      hybrids) screening parameters, and on an extended array of physical phenomena:
      pressure- and doping-induced insulator-to-metal and structural phase transitions,
      multiferroism, surface and interface effects, charge ordering and localization
      effects, and spin-orbit coupling. 

PMID- 24871430
TI  - Environmental effects on stem water deficit in co-occurring conifers exposed to
      soil dryness.
AB  - We monitored dynamics of stem water deficit (DeltaW) and needle water potential
      (Psi) during two consecutive growing seasons (2011 and 2012) in a dry inner
      Alpine environment (750 m above sea level, Tyrol, Austria), where Pinus
      sylvestris, Picea abies and Larix decidua form mixed stands. DeltaW was extracted
      from stem circumference variations, which were continuously recorded by
      electronic band dendrometers (six trees per species) and correlations with
      environmental variables were performed. Results revealed that (i) DeltaW reached
      highest and lowest values in P. abies and L. decidua, respectively, while mean
      minimum water potential (Psi(ea)) amounted to -3.0 MPa in L. decidua and -1.8 MPa
      in P. abies and P. sylvestris. (ii) DeltaW and Psi(ea) were significantly
      correlated in P. abies (r = 0.630; P = 0.038) and L. decidua (r = 0.646; P =
      0.032). (iii) In all species, DeltaW reached highest values in late summer and
      was most closely related to temperature (P < 0.001). Results indicate that all
      species were undergoing water limitations as measured by increasing DeltaW
      throughout the growing season, whereby P. abies most strongly drew upon water
      reserves in the living tissues of the bark. Quite similar DeltaW developed in
      drought-sensitive L. decidua and drought-tolerant P. sylvestris indicate that
      various water storage locations are depleted in species showing different
      strategies of water status regulation, i.e. anisohydric vs. isohydric behavior,
      respectively, and/or water uptake efficiency differs among these species. Close
      coupling of DeltaW to temperature suggests that climate warming affects plant
      water status through its effect on atmospheric demand for moisture.

PMID- 24871432
TI  - Mindfulness: another tool in the case managers' toolbox.
AB  - Case managers and their patients/clients may benefit from the practice of
      mindfulness-based stress reduction. Recently, using MRI technology, science has
      found that the gray matters in specific areas of the brain increased from
      premindfulness training to postmindfulness training. The area affected improves
      regions involved with learning and memory processes, modulation of emotional
      control, and the process of awareness. This can be another tool in the case
      management toolbox. 

PMID- 24871429
TI  - Autoinducer-2 plays a crucial role in gut colonization and probiotic
      functionality of Bifidobacterium breve UCC2003.
AB  - In the present study we show that luxS of Bifidobacterium breve UCC2003 is
      involved in the production of the interspecies signaling molecule autoinducer-2
      (AI-2), and that this gene is essential for gastrointestinal colonization of a
      murine host, while it is also involved in providing protection against Salmonella
      infection in Caenorhabditis elegans. We demonstrate that a B. breve luxS
      insertion mutant is significantly more susceptible to iron chelators than the WT
      strain and that this sensitivity can be partially reverted in the presence of the
      AI-2 precursor DPD. Furthermore, we show that several genes of an iron starvation
      induced gene cluster, which are downregulated in the luxS-insertion mutant and
      which encodes a presumed iron-uptake system, are transcriptionally upregulated
      under in vivo conditions. Mutation of two genes of this cluster in B. breve
      UCC2003 renders the derived mutant strains sensitive to iron chelators while
      deficient in their ability to confer gut pathogen protection to Salmonella
      infected nematodes. Since a functional luxS gene is present in all tested members
      of the genus Bifidobacterium, we conclude that bifidobacteria operate a LuxS
      mediated system for gut colonization and pathogen protection that is correlated
      with iron acquisition. 

PMID- 24871433
TI  - Trauma-informed care: a paradigm shift needed for services with homeless
      veterans.
AB  - PURPOSE OF STUDY: Exposure to traumatic events is a highly prevalent, although
      often overlooked, aspect in the lives of homeless veterans. In this study, the
      prevalence and correlates of potentially traumatic events, including
      posttraumatic stress disorder, in the homeless veteran population are presented.
      FINDINGS/CONCLUSIONS: Presently, there exists a lack of trauma-informed case
      management services for homeless veterans. Failing to recognize the association
      between trauma and homelessness may lead to further victimization, exacerbate
      mental health symptomology, and hinder a provider's ability to effectively
      intervene on behalf of homeless veterans. IMPLICATIONS FOR CASE MANAGEMENT:
      Subgroups of homeless veterans such as those who served in the Vietnam and post
      Vietnam era, more recent returnees from Iraq and Afghanistan, women, rural
      residing veterans, and those who are justice involved, are discussed for unique
      trauma histories and service needs. Barriers to receiving trauma-informed care
      among homeless veterans are reviewed. Information to assist providers in
      assessing trauma histories and current best practices in the treatment of
      posttraumatic stress disorder are noted. Suggestions for how this document can be
      used in varied organizational settings are made.

PMID- 24871435
TI  - Reducing moral distress in case managers.
AB  - PURPOSE: Moral distress can be caused by ethical conflicts that are common in
      acute care settings. Hospital case managers are unique caregivers in hospital
      environments. Case managers are advocates who coordinate organizational,
      clinical, and personal standards. Ethical conflicts embedded in performing
      delegated responsibilities are burdensome, therefore creating a risk for moral
      distress. Mindfulness education is suggested as a meaningful process to mitigate
      moral distress for frontline caregivers. PRIMARY PRACTICE SETTING: Moral distress
      describes organizational, clinical, and personal ethical conflicts and
      constraints a caregiver experiences in acute care settings. FINDINGS/CONCLUSIONS:
      Theories and tools addressing moral distress continue to evolve. Researchers are
      revising and creating new tools defining moral distress, but triggers and
      responses vary among ethically conflicted nurses. Causes of moral distress
      include burden and frequency of ethical conflict and constraints leading to
      depression, anger, and impaired perception of competency. Little attention has
      been given to hospital case management as a caregiving profession at risk. The
      ethical dilemmas research defines as "risks" for moral distress are prevalent in
      the ethical responsibilities delegated to case management. IMPLICATIONS FOR CASE
      MANAGEMENT PRACTICE: The hospital case manager's responsibilities contain
      compelling and competing ethical priorities of patient advocate, organization
      representative, and competent professional. General suggestions to moderate moral
      distress have been inadequate in mitigating the problem, because they do not
      adequately offer the caregiver a way to identify and process moral distress.
      Causes and conditions describing moral distress due to ethical conflicts are
      similar to themes of suffering and awareness identified in mindfulness and other
      reflective exercises. A workshop series introducing reflective practices is an
      appropriate approach to reduce negative outcomes of moral distress in caregiver
      roles.

PMID- 24871437
TI  - It was the best of times, it was the worst of times: a difficult journey to the
      heartbeat of what matters in case management.

PMID- 24871438
TI  - HIPAA compliance practice tips.

PMID- 24871439
TI  - A valuable education: Teaching case management to tomorrow's clinicians.

PMID- 24871440
TI  - Why do we still eat our young?: strategies and interventions to decrease
      workplace bullying.

PMID- 24871441
TI  - Advances in some common chronic liver diseases. Preface.

PMID- 24871442
TI  - New perspective on the natural course of chronic HBV infection.
AB  - Chronic hepatitis B virus (HBV) infection is a significant threat to public
      health and an enormous burden on society. Mechanisms responsible for chronic HBV
      infection remain poorly understood. A better understanding of the natural course
      of chronic HBV infection may shed new light on the mechanisms underlying this
      disease and help in designing new antiviral strategies. Natural course of chronic
      HBV infection is conventionally viewed as an uninterrupted process that is
      usually marked by HBV e antigen (HBeAg) seroconversion or characterized by
      different phases associated with assumed host responses to HBV infection.
      However, none of these descriptions captures or highlights the core events that
      determine the natural course of chronic HBV infection. In this review, we briefly
      present the current knowledge on this subject and explain the significance and
      implication of events that occur during infection. A pre-core mutant becomes
      predominant in the viral population following elimination of the wild-type virus
      in duck hepatitis B virus-chronically infected animals. The coupled events in
      which first there is viral clearance that clears wild-type virus and then there
      is the reinfection of wild-type virus cleared livers with mutant virus are highly
      relevant to understanding of the natural course of chronic HBV infection under
      both treated and untreated conditions. In our new perspective, a general natural
      course of chronic HBV infection comprises cycles of viral clearance and
      reinfection, and such cycles prolong the chronic HBV infection course. Reviewing
      published data on the natural course of chronic HBV infection can reduce the
      possibility of missing important points in the initial data interpretation. 

PMID- 24871444
TI  - Current recommendations of managing HBV infection in preconception or pregnancy.
AB  - Hepatitis B remains a leading cause of cirrhosis, hepatocellular carcinoma and
      liver transplantation worldwide. Management of chronic hepatitis B during
      pregnancy is challenging. Transmission of hepatitis B to infants still occurs
      perinatally although immunoprophylaxis is widely available for infants born to
      mothers with chronic hepatitis B infection. The emerging data suggest that
      initiation of antiviral therapy in the beginning of the third trimester in highly
      viremic mothers can prevent immunoprophylaxis failure in their infants. The
      available drug safety data show that lamivudine, telbivudine and tenofovir are
      generally safe to be used during the pregnancy. In order to minimize the fetal
      exposure to the antiviral medication, antiviral therapy during the pregnancy
      should be limited to a selected group of patients with cirrhosis, high hepatitis
      B viral load, or prior history immunoprophylaxis failure. An elective Caesarean
      section may reduce the risk of perinatal transmission. For those females planning
      for pregnancy or in early stage of pregnancy, communication and follow-up among
      obstetrician, gastroenterologist, and primary care physician are important. In
      this article, we will review the features of hepatitis B infection before, during
      and after the pregnancy; the risk factors that increase mother-to-child
      transmission; safety data on antiviral drug use during pregnancy; and the
      potential role of Caesarean section in selected cases.

PMID- 24871445
TI  - Advances in newly developing therapy for chronic hepatitis C virus infection.
AB  - Chronic hepatitis C virus (HCV) infection afflicts a reported 170 million people
      worldwide and is often complicated by cirrhosis and hepatocellular carcinoma.
      Morbidity and mortality are decreased with the successful treatment of chronic
      HCV infection. Increased understanding of the HCV has allowed further development
      of new direct-acting antiviral (DAA) agents against the HCV and has also allowed
      the development of IFN-free oral treatment regimens. In late 2013 the first
      nucleotide polymerase inhibitor regimen with RBV alone for genotypes 2/3 and in
      combination with a 12-week regimen of PEG-IFN + RBV for genotypes 1, 4 was
      approved for use in the US. A number of promising new DAA regimens which are IFN
      free are in phase 3 development and the first will likely be approved for use in
      the US in 2014. The currently approved regimens are discussed in detail and
      currently available data on future regimens are reviewed herein. 

PMID- 24871443
TI  - Current hepatitis B treatment guidelines and future research directions.
AB  - Hepatitis B virus (HBV) infection causes a tremendous clinical burden across the
      world with more than half a million people dying annually from HBV related
      disease. Significant advances have been made in HBV treatment in the past decade
      and several guidelines have been published by professional societies and expert
      panels. Although these recommendations have been valuable to help optimize HBV
      treatment, there is discordance in treatment criteria and many patients infected
      with HBV may fall outside of these recommendations. This paper systematically
      reviews the natural history of the disease and compares and contrasts the
      recommendations for initiation of treatment from the various societies. There is
      also discussion of special groups that require particular consideration and some
      of the open research questions and future research directions within the field. 

PMID- 24871447
TI  - Preoperative fibrinogen and morbidity in patients with residual platelet
      inhibition undergoing off-pump coronary artery bypass grafting: cause or effect?

PMID- 24871446
TI  - Integrated strategy of pH-shift and glucose feeding for enhanced production of
      bioactive Antrodin C in submerged fermentation of Antrodia camphorata.
AB  - Antrodin C is one of the most potent bioactive components produced by the
      medicinal mushroom Antrodia camphorata. However, almost all studies in this field
      have focused on the biological activity of Antrodin C and relatively rare
      information has been reported regarding the biosynthetic process of Antrodin C.
      In this study, the strategies of pH-shift and glucose feeding for enhanced
      production of Antrodin C in submerged fermentation of A. camphorata were
      successfully applied in stirred bioreactors. The critical parameters for pH-shift
      and glucose feeding were systematically investigated. On one hand, the optimal
      culture pH for cell growth was distinct with Antrodin C biosynthesis and the
      maximum Antrodin C production was obtained by maintaining the first-stage culture
      at initial pH 4.5 and adjusted to 6.0 at day 8. On the other hand, it was
      beneficial for the Antrodin C accumulation with the initial glucose concentration
      of 40 g/L and feeding glucose to keep the residual sugar above 10 g/L. The
      maximum Antrodin C production (1,549.06 mg/L) was about 2.1-fold higher than that
      of control in 15-L stirred bioreactors by taking advantage of the integrated
      strategy of pH-shift and glucose feeding. These results would be helpful for the
      design of a highly efficient Antrodin C biosynthesis process.

PMID- 24871449
TI  - High prevalence of the SCN5A E1784K mutation in school children with long QT
      syndrome living on the Okinawa islands.
AB  - BACKGROUND: Genetic testing for long QT syndrome (LQTS) is now in clinical
      practice. We conducted molecular genetic analyses to definitively diagnose LQTS
      and to determine its subtypes for gene-specific treatment. We conducted a
      retrospective study to determine the characteristics of schoolchildren with LQTS
      living on the Okinawa Islands. METHODS AND RESULTS: The study population included
      children identified in a school-based electrocardiographic (ECG) screening
      program for cardiovascular diseases who were referred to Okinawa Children's
      Medical Center between 2007 and 2012; 23 children met the diagnostic criteria for
      LQTS. Of them, 17 were genotype-positive and 14 were found to harbor
      theSCN5AE1784K mutation exclusively among the LQTS genotype-positive children.
      The children were divided into genotype-positive and -negative groups. Clinical
      characteristics and ECG data were analyzed and compared. The median Schwartz
      score was 3. The median QT interval was 521 ms. CONCLUSIONS: The major finding is
      that the prevalent subtype of LQTS in Okinawa is discordant with other cohorts
      living in other regions of Japan or overseas. We cannot exclude the possibility
      of the presence of a specific founder mutation in this geographically clustered
      population, particularly considering that the hospital is the only tertiary heart
      center for children in Okinawa. However, this uniquely high prevalence of
      theSCN5AE1784K mutation serves as a compelling justification to conduct a larger
      study.

PMID- 24871450
TI  - Modular assembly of optical nanocircuits.
AB  - A key element enabling the microelectronic technology advances of the past
      decades has been the conceptualization of complex circuits with versatile
      functionalities as being composed of the proper combination of basic 'lumped'
      circuit elements (for example, inductors and capacitors). In contrast, modern
      nanophotonic systems are still far from a similar level of sophistication,
      partially because of the lack of modularization of their response in terms of
      basic building blocks. Here we demonstrate the design, assembly and
      characterization of relatively complex photonic nanocircuits by accurately
      positioning a number of metallic and dielectric nanoparticles acting as modular
      lumped elements. The nanoparticle clusters produce the desired spectral response
      described by simple circuit rules and are shown to be dynamically reconfigurable
      by modifying the direction or polarization of impinging signals. Our work
      represents an important step towards extending the powerful modular design tools
      of electronic circuits into nanophotonic systems. 

PMID- 24871451
TI  - Association between flavonoid-rich fruit and vegetable consumption and total
      serum bilirubin.
AB  - Emerging work demonstrates that serum bilirubin is a novel biomarker implicated
      in cardiovascular and metabolic diseases. However, we have a limited
      understanding of the influence of flavonoid-rich fruit and vegetable consumption
      on bilirubin levels, which was the purpose of this study. Data from the 2003 to
      2006 National Health and Nutrition Examination survey were used (n = 1783; 18-85
      years of age), with analyses performed in 2014. Total serum bilirubin was
      measured from a blood sample. Using a food frequency questionnaire (FFQ), a
      flavonoid index variable was created summing the frequency of consumption of
      flavonoid-rich foods. After adjustments, greater consumption of flavonoid-rich
      fruits and vegetables was positively associated with bilirubin levels. Our
      findings suggest an association between flavonoid-rich fruit and vegetable
      consumption and bilirubin levels. If confirmed by prospective and experimental
      studies, then regular consumption of flavonoid-rich fruits and vegetables should
      be promoted to increase levels of bilirubin. 

PMID- 24871452
TI  - Chemical composition, crystal structure, and their relationships with the
      intrinsic properties of spinel-type crystals based on bond valences.
AB  - Spinel-type crystals may possess complex and versatile chemical composition and
      crystal structure, which leads to difficulty in constructing relationships among
      the chemical composition, crystal structure, and intrinsic properties. In this
      work, we develop new empirical methods based on bond valences to estimate the
      intrinsic properties, namely, compressibility and thermal expansion of complex
      spinel-type crystals. The composition-weighted average of bond force constants in
      tetrahedral and octahedral coordination polyhedra is derived as a function of the
      composition-weighted average of bond valences, which can be calculated according
      to the experimental chemical composition and crystal structural parameters. We
      discuss the coupled effects of tetrahedral and octahedral frameworks on the
      aforementioned intrinsic properties. The bulk modulus could be quantitatively
      calculated from the composition-weighted average of bond force constants in
      tetrahedral and octahedral coordination polyhedra. In contrast, a quantitative
      estimation of the thermal expansion coefficient could be obtained from the
      composition-weighted average of bond force constants in octahedral coordination
      polyhedra. These empirical methods have been validated by the results obtained
      for a new complex quaternary spinel-type oxynitride Mg0.268Al2.577O3.733N0.267 as
      well as MgAl2O4 and Al2.85O3.45N0.55 from the literature. Further, these
      empirical methods have the potential to be extensively applied in other types of
      complex crystals. 

PMID- 24871453
TI  - HOF.CH3CN: probably the best oxygen transfer agent organic chemistry has to
      offer.
AB  - The complex HOF.CH3CN is readily obtained by bubbling dilute fluorine into
      aqueous acetonitrile solution. It does not have to be purified or isolated, and
      its solution can react as is, after the concentration has been establish by any
      iodometric method. It is the only reagent possessing a distinctive positive
      oxygen species. This enables electrophilic oxygen transfer with results no other
      reagent can match. HOF.CH3CN demonstrates its ability in epoxidations that either
      could not be performed before or could only obtained 5 orders of magnitude
      slower. This complex is also an excellent tool for oxygenation of compounds at
      the alpha position of a carbonyl, including the synthesis of some hard-to-come-by
      indanediones, which are important for fingerprint visualization on paper.
      HOF.CH3CN proves itself as a very efficient reagent for oxygenating tertiary
      nitrogen atoms both in aliphatic (including azides) and in aromatic amines, which
      could not be accomplished despite many attempts in the last 50 years. Oxygenation
      of two tertiary nitrogen atoms in the same molecule also becomes feasible as
      demonstrated for various phenanthrolines, bipyridines, diazafluorenones, and
      quinoxalines. It was also used to oxygenate primary amines, and because of the
      exceptionally mild conditions, it could transform vicinal aliphatic diamines to
      vicinal dinitro derivatives as well as amino acids to the corresponding nitro
      ones, practically unknown transformations before. Its ability to react with
      azines and hydrazones and convert them to the original carbonyls helped to
      establish these groups as good protecting tools for a variety of carbonyls.
      HOF.CH3CN excels in oxygenation of various sulfur and selenium compounds that
      could not be oxygenated in the past. The selectivity of the oxidation is quite
      good, and if there are alcohols, double bonds, and sulfides in the same molecule,
      usually the sulfur atom will be attacked first. Of special interest is the
      reaction with oligothiophenes resulting at will in either [all]-S,S
      dioxooligothiophenes or in partially oxygenated ones. Some of these last
      derivatives have the narrowest HOMO-LUMO gap of all oligothiophenes tested, a
      very desirable feature. This reagent can also oxidize thiols or disulfides to
      either sulfonic or sulfinic acids at will, all in seconds and in very high
      yields. Since the oxygen atom of HOF.CH3CN originates in water, it is very easy
      and relatively inexpensive to introduce the heavy oxygen isotope in many sites of
      a variety of molecules, some of them quite important. The (18)O tirapazamine and
      any desirable alcohol, R(Ar)(18)OH, are two examples.

PMID- 24871454
TI  - Is bone loss linked to chronic inflammation in antiretroviral-naive HIV-infected
      adults? A 48-week matched cohort study.
AB  - OBJECTIVE: Antiretroviral therapy (ART) has been implicated in bone loss in HIV.
      The role of inflammation and vitamin D is unclear and better investigated in ART
      naive individuals. DESIGN AND METHODS: This is a 48-week, prospective cohort
      study to compare baseline and change in hip and spine bone mineral density (BMD)
      measured by dual-energy X-ray absorptiometry in HIV-infected, ART-naive adults
      and healthy controls matched by age, sex, and race. We also studied associations
      between bone loss and inflammation markers and plasma 25-hydroxyvitamin D
      [25(OH)D] using logistic regression. RESULTS: Forty-seven HIV-infected adults and
      41 controls were included. Baseline 25(OH)D, BMD at total hip, trochanter, and
      spine, and prevalence of osteopenia and osteoporosis were similar between groups.
      In the HIV-infected group, total hip and trochanter, but not spine, BMD decreased
      over 48 weeks [hip -0.005 (-0.026-0.008) g/cm2, P = 0.02 within group; trochanter
      -0.013 (-0.03-0.003), P < 0.01]. BMD did not change at any site within controls.
      The HIV-infected group was more likely to have bone loss at the trochanter (P =
      0.03). This risk persisted after adjustment for age, sex, race, BMI, smoking, and
      hepatitis C (odds ratio 4, 95% confidence interval 1.2-15.8). In the HIV-infected
      group, higher interleukin-6 concentrations (P = 0.04) and Caucasian race (P <
      0.01) were independently associated with progression to osteopenia or
      osteoporosis, but not 25(OH)D levels. CONCLUSION: BMD at the total hip and
      trochanter sites decreased in the HIV-infected, ART-naive adults, but not
      controls, over this 48-week study. Higher serum interleukin-6 concentrations were
      associated with progression to osteopenia or osteoporosis status in the HIV
      infected group.

PMID- 24871456
TI  - High prevalence of subtype F in newly diagnosed HIV-1 persons in northwest Spain
      and evidence for impaired treatment response.
AB  - HIV-1 non-B subtype variants were found in 37.8% of 296 newly diagnosed persons
      in northwest Spain over the past 5 years. Subtype F was the most prevalent non-B
      subtype (29.6%) and displayed preferential transmission among MSM. Virologic
      response rates to antiretroviral therapy were lower among F subtypes compared to
      B subtypes at weeks 24 (31% vs. 78.3%), 48 (51.7% vs. 85.2%), and 96 (61.1% vs.
      94.3%) of therapy. Subtype F was independently associated with virological
      response at 24 weeks. 

PMID- 24871457
TI  - Chronopotentiometric carbonate detection with all-solid-state ionophore-based
      electrodes.
AB  - We present here for the first time an all-solid-state chronopotentiometric ion
      sensing system based on selective ionophores, specifically for the carbonate
      anion. A chronopotentiometric readout is attractive because it may allow one to
      obtain complementary information on the sample speciation compared to zero
      current potentiometry and detect the sum of labile carbonate species instead of
      only ion activity. Ferrocene covalently attached to the PVC polymeric chain acts
      as an ion-to-electron transducer and provides the driving force to initiate the
      sensing process at the membrane-sample interface. The incorporation of a
      selective ionophore for carbonate allows one to determine this anion in a
      background electrolyte. Various inner electrolyte and all-solid-state-membrane
      configurations are explored, and localized carbonate depletion is only observed
      for systems that do not contain ion-exchanger additives. The square root of the
      transition times extracted from the inflection point of the chronopotentiograms
      as a function of carbonate specie concentration follows a linear relationship.
      The observed linear range is 0.03-0.35 mM in a pH range of 9.50-10.05. By
      applying the Sand equation, the diffusion coefficient of carbonate is calculated
      as (9.03 +/- 0.91) 10(-6) cm(2) s(-1), which corresponds to the established
      value. The reproducibility of assessed carbonate is better than 1%. Additionally,
      carbonate is monitored during titrimetric analysis as a precursor to an in situ
      environmental determination. Based on these results, Fc-PVC membranes doped with
      ionophores may form the basis of a new family of passive/active all-solid-state
      ion selective electrodes interrogated by a current pulse. 

PMID- 24871455
TI  - Programmed death-1 expression on CD4+ and CD8+ T cells in treated and untreated
      HIV disease.
AB  - BACKGROUND: There is intense interest in the role of programmed death 1 (PD-1) in
      causing persistent T-cell dysfunction in HIV infection. However, the impact of
      HIV infection and antiretroviral treatment (ART) on the expression of PD-1 on T
      cells is still poorly defined. METHODS: PD-1 was measured longitudinally in a
      cohort of recently HIV-infected individuals (n = 121) who started ART early (<6
      months after infection) vs. later (>=2 years after infection). PD-1 was also
      measured cross-sectionally in a diverse cohort of chronically HIV-infected adults
      (n = 206). RESULTS: PD-1 expression levels were high on CD8+ T cells during early
      HIV infection. PD-1 levels increased on both CD4+ and CD8+ T cells populations in
      those who delayed therapy (11 and 10%/year, respectively). PD-1 levels declined
      and were similar in those treated early vs. late after 1 year of ART. In both
      cohorts, PD-1 expression on CD4+ T cells was associated with CD4+ T-cell
      activation (CD38+HLA-DR+) and inversely with CD4+ cell count. In contrast, PD-1
      expression on CD8+ T cells was most strongly associated with CD8+ T-cell
      activation and with plasma viral load in viremic individuals. CONCLUSION: Across
      two large cohorts of untreated and treated individuals, we found consistent
      associations between HIV RNA levels, CD8+ T-cell activation and PD-1 expression
      on CD8+ T cells. In contrast, CD4+ T-cell counts and CD4+ T-cell activation were
      more consistent correlates of PD-1 expression on CD4+ T cells. PD-1 expression
      appears to be driven by both direct antigen and homeostatic pathways.

PMID- 24871458
TI  - Maternal perception of fetal movement type: the effect of gestational age and
      maternal factors.
AB  - OBJECTIVE: To assess maternal perception of fetal movement types and its
      association with maternal factors in normal pregnancies with good pregnancy
      outcome. METHODS: This study was conducted on 729 normotensive singleton pregnant
      women with good pregnancy outcome who had referred for prenatal visit. After
      completing a questionnaire, the participants were asked to count fetal movements
      for 1 h/3 times/day. They were also asked to identify the type of fetal movement:
      general body movement (GBM) (rolling and stretching/strong), isolated limb
      movement (ILM; simple flutter or kicks/weak), trunk movement (TM) (strong jab,
      startle/strong), or hiccup movement (HM) (high frequency and rapid/weak). All the
      participants were followed till delivery to exclude pregnant women with preterm
      birth and/or small for gestational age from the study. RESULTS: 90.8% of
      participants perceived GBM, which was independently associated with maternal
      unemployment (OR = 2.28, 95% CI = 1.18-4.4). 74.2% of participants perceived TM,
      which was associated with multiparity (OR = 1.69, 95% CI = 1.18-2.4). 86.3%
      perceived ILM, which was independently associated with maternal unemployment (OR
      = 2.67, 95% CI = 1.53-4.68), lower gestational age (OR = 2.17, 95% CI = 1.28
      3.67), perception of fetal movements at night (OR = 2.05, 95% CI = 1.27-3.32),
      and multiparity (OR = 1.68, 95% CI = 1.04-2.72). 36.6% perceived HM, which was
      independently associated with higher gestational age (OR = 1.71, 95% CI = 1.2
      2.44). CONCLUSIONS: Most pregnant women could discriminate changes in fetal
      movement type that follow a general pattern through the third gestational
      trimester, however this can be affected by maternal employment, parity and time
      of perception.

PMID- 24871459
TI  - The effects of direct and indirect road transport consignment in combination with
      feed withdrawal in young dairy calves.
AB  - Male dairy calves may be transported from their farm of origin at a young age.
      This process may involve an extended period off feed and indirect consignment
      through an intermediate facility, prompting potential welfare concerns. To assess
      the impact of transport, 59 male Holstein-Friesian dairy calves (5-9 d old) were
      either (1) held in situ on farm (control); (2) transported for 6 h; (3)
      transported for 12 h; or (4) transported for 1 h to a holding facility where they
      were kept for 6 h and then transported for 5 h. All treatments included a 30-h
      period of feed (milk) withdrawal, and calf responses were measured over time from
      before their last feed until the completion of the study after the transport and
      feed withdrawal periods. Apart from increases in serum creatine kinase in calves
      transported for 12 h, transported calves generally did not differ in blood
      concentrations of glucose, beta-hydroxybutyrate, lactate, total protein or in
      packed cell volume, compared with controls (P>0.05). Calf responses to the
      indirect consignment treatment did not differ from those of other transported
      calves. Withdrawal of feed for 30 h caused calves to lose 6% of body weight;
      blood glucose varied from 3.96 mmol/l immediately before daily feeding to 5.46
      mmol/l at 3 h post feeding, and then declined to 3.43 mmol/l at 30 h. Calves lay
      down for 22-32% of the time during transport, and did not show a rebound effect
      in lying behaviour post arrival in comparison with controls. Best practice
      transport of 6-12 h duration, including indirect consignment via a holding
      facility, did not significantly affect calf blood biochemistry and metabolism in
      comparison with untransported animals. However, extending the time off feed
      beyond the daily feeding interval resulted in reduced blood glucose
      concentrations, suggesting that time off feed needs to be carefully managed in
      young transported dairy calves.

PMID- 24871460
TI  - Marine and semi-synthetic hydroxysteroids as new scaffolds for pregnane X
      receptor modulation.
AB  - In recent years many sterols with unusual structures and promising biological
      profiles have been identified from marine sources. Here we report the isolation
      of a series of 24-alkylated-hydroxysteroids from the soft coral Sinularia
      kavarattiensis, acting as pregnane X receptor (PXR) modulators. Starting from
      this scaffold a number of derivatives were prepared and evaluated for their
      ability to activate the PXR by assessing transactivation and quantifying gene
      expression. Our study reveals that ergost-5-en-3beta-ol (4) induces PXR
      transactivation in HepG2 cells and stimulates the expression of the PXR target
      gene CYP3A4. To shed light on the molecular basis of the interaction between
      these ligands and PXR, we investigated, through docking simulations, the binding
      mechanism of the most potent compound of the series, 4, to the PXR. Our findings
      provide useful functional and structural information to guide further
      investigations and drug design. 

PMID- 24871461
TI  - Nine new and five known polyketides derived from a deep sea-sourced Aspergillus
      sp. 16-02-1.
AB  - Nine new C9 polyketides, named aspiketolactonol (1), aspilactonols A-F (2-7),
      aspyronol (9) and epiaspinonediol (11), were isolated together with five known
      polyketides, (S)-2-(2'-hydroxyethyl)-4-methyl-gamma-butyrolactone (8),
      dihydroaspyrone (10), aspinotriol A (12), aspinotriol B (13) and chaetoquadrin F
      (14), from the secondary metabolites of an Aspergillus sp. 16-02-1 that was
      isolated from a deep-sea sediment sample. Structures of the new compounds,
      including their absolute configurations, were determined by spectroscopic
      methods, especially the 2D NMR, circular dichroism (CD), Mo2-induced CD and
      Mosher's 1H NMR analyses. Compound 8 was isolated from natural sources for the
      first time, and the possible biosynthetic pathways for 1-14 were also proposed
      and discussed. Compounds 1-14 inhibited human cancer cell lines, K562, HL-60,
      HeLa and BGC-823, to varying extents. 

PMID- 24871462
TI  - Coeliac disease-associated polymorphisms influence thymic gene expression.
AB  - Significant associations between coeliac disease (CD) and single nucleotide
      polymorphisms (SNPs) distributed over 40 genetic regions have been established.
      The majority of these SNPs are non-coding and 20 SNPs were, by expression
      quantitative trait loci (eQTL) analysis, found to harbour cis regulatory
      potential in peripheral blood mononuclear cells (PBMC). Almost all regions
      contain genes with an immunological relevant function, of which many act in the
      same biological pathways. One such pathway is T-cell development in the thymus, a
      pathway previously not explored in CD pathogenesis. The aim of our study was to
      explore the regulatory potential of the CD-associated SNPs (n=50) by eQTL
      analysis in thymic tissue from 42 subjects. In total, 43 nominal significant
      (P<0.05) eQTLs were found within 24 CD-associated chromosomal regions,
      corresponding to 27 expression-altering SNPs (eSNPs) and 40 probes (eProbes) that
      represents 39 unique genes (eGenes). Nine significant probe-SNP pairs
      (corresponding to 8 eSNPs and 7 eGenes) overlapped with previous findings in PBMC
      (rs12727642-PARK7, rs296547-DDX59, rs917997-IL18RAP, rs842647-AHSA2, rs13003464
      AHSA2, rs6974491-ELMO1, rs2074404-NSF (two independent probes) and rs2298428
      UBE2L3). When compared across more tissues, we found that 14 eQTLs could
      represent potentially novel thymus-specific eQTLs. This implies that CD risk
      polymorphisms could affect gene regulation in thymus. 

PMID- 24871463
TI  - GWAS identifies novel SLE susceptibility genes and explains the association of
      the HLA region.
AB  - In a genome-wide association study (GWAS) of individuals of European ancestry
      afflicted with systemic lupus erythematosus (SLE) the extensive utilization of
      imputation, step-wise multiple regression, lasso regularization and increasing
      study power by utilizing false discovery rate instead of a Bonferroni multiple
      test correction enabled us to identify 13 novel non-human leukocyte antigen (HLA)
      genes and confirmed the association of four genes previously reported to be
      associated. Novel genes associated with SLE susceptibility included two
      transcription factors (EHF and MED1), two components of the NF-kappaB pathway
      (RASSF2 and RNF114), one gene involved in adhesion and endothelial migration
      (CNTN6) and two genes involved in antigen presentation (BIN1 and SEC61G). In
      addition, the strongly significant association of multiple single-nucleotide
      polymorphisms (SNPs) in the HLA region was assigned to HLA alleles and serotypes
      and deconvoluted into four primary signals. The novel SLE-associated genes point
      to new directions for both the diagnosis and treatment of this debilitating
      autoimmune disease. 

PMID- 24871470
TI  - Diet pattern and longevity: do simple rules suffice? A commentary.
AB  - Nutritionism reduces dietary advice to statements about a few nutrients, with
      sometimes unintended implications for science, industry, and the public. Although
      reductionist questions about nutrition are legitimate scientifically, a nutrient
      focus in the public arena forces the food industry to compete with the use of
      nutrient statements. Consumers must interpret information that may not be correct
      or relevant. The theory of food synergy, which postulates that the many
      constituents of individual foods and dietary patterns act together on health,
      leads to the idea that dietary policy would be clearer if it focused on foods. To
      illustrate this method, the food-based A Priori Diet Quality Score was described
      in the Iowa Women's Health Study; a substantial total mortality reduction for
      increasing quartiles of the score was found. The simple food-based rules implied
      in this a priori score support minimizing meat, salt, added sugar, and heavily
      processed foods while emphasizing phytochemical-rich foods. These principles
      could help improve nutrition policy, help industry to supply better food, and
      help to focus future scientific research. Although an understanding of what foods
      are best for health is a step forward in nutrition, other major challenges
      remain, including getting high-quality food to the masses and food
      sustainability. 

PMID- 24871472
TI  - Protein production: planet, profit, plus people?
AB  - Food sustainability and food security are increasingly in the spotlight and
      increasingly intertwined. According to some projections we will need to nearly
      double food production in the next 4 decades. This article argues that protein
      production and consumption are pivotal to sustainability, because anthropogenic
      contributions to the nitrogen cycle are 100-200% compared with a contribution of
      1-2% to the carbon cycle by mineral fuel combustion, with biodiversity as the
      main casualty. Because 1 kg animal protein requires ~ 6 kg plant protein, its
      large-scale production by means of factory farming is a major driver of
      biodiversity loss, climate change, and freshwater depletion. Furthermore,
      intensive livestock production is associated with antibiotics resistance and
      increasing incidence of emerging diseases. Therefore, a "reversed" diet
      transition back to less animal protein could make a difference. Some European
      countries, such as the United Kingdom, Sweden, and The Netherlands, have
      published integrated policy reports addressing food security, sustainability, and
      health combined. The food industry is focusing on food safety and increasingly on
      sustainability. An important issue is consumer communication, because consumer
      "framing" is radically different from that of governmental and industrial policy
      makers. There is no "one size fits all." A huge range of differences exists
      between countries and between distinct groups of consumers within countries;
      getting consumers to change their diets in a more sustainable direction is likely
      to require much more than gentle nudging. National governments and the United
      Nations should assume their responsibilities and initiate a global strategy
      integrating sustainability, food security, nutrition, and equity. To date, the
      profit pillar of sustainability has taken precedence over planet and people. It
      is time to redress the balance.

PMID- 24871471
TI  - Genistein inhibits human prostate cancer cell detachment, invasion, and
      metastasis.
AB  - Prostate cancer (PCa) is the most commonly diagnosed cancer in men in the United
      States and the second leading cause of cancer death. Death is not caused by the
      primary tumor but rather by the formation of distinct metastatic tumors.
      Therefore, prevention of metastasis is of utmost importance. The natural product
      genistein, found in high amounts in soy products, has been implicated in
      preventing PCa formation and metastasis in men who consume high amounts of soy.
      In vitro studies and in vivo rodent models that used human PCa cells, as well as
      prospective human clinical trials, provide a mechanistic explanation directly
      supporting genistein as an antimetastatic agent. Specifically, our group showed
      that genistein inhibits cell detachment, protease production, cell invasion, and
      human PCa metastasis at concentrations achieved in humans with dietary intake.
      Finally, phase I and phase II clinical trials conducted by us and others showed
      that concentrations of genistein associated with antimetastatic efficacy in
      preclinical models are achievable in humans, and treatment with genistein
      inhibits pathways that regulate metastatic transformation in human prostate
      tissue. 

PMID- 24871464
TI  - The CLRX.1/NOD24 (NLRP2P) pseudogene codes a functional negative regulator of NF
      kappaB, pyrin-only protein 4.
AB  - Pseudogenes are duplicated yet defunct copies of functional parent genes.
      However, some pseudogenes have gained or retained function. In this study, we
      consider a functional role for the NLRP2-related, higher primate-specific,
      processed pseudogene NLRP2P, which is closely related to Pyrin-only protein 2
      (POP2/PYDC2), a regulator of nuclear factor-kappaB (NF-kappaB) and the
      inflammasome. The NLRP2P open-reading frame on chromosome X has features
      consistent with a processed pseudogene (retrotransposon), yet encodes a 45-amino
      acid, Pyrin-domain-related protein. The open-reading frame of NLRP2P shares 80%
      identity with POP2 and is under purifying selection across Old World primates.
      Although widely expressed, NLRP2P messenger RNA is upregulated by
      lipopolysaccharide in human monocytic cells. Functionally, NLRP2P impairs NF
      kappaB p65 transactivation by reducing activating phosphorylation of RelA/p65.
      Reminiscent of POP2, NLRP2P reduces production of the NF-kappaB-dependent
      cytokines tumor necrosis factor alpha and interleukin (IL)-6 following toll-like
      receptor stimulation. In contrast to POP2, NLRP2P fails to inhibit the ASC
      dependent NLRP3 inflammasome. In addition, beyond regulating cytokine production,
      NLRP2P has a potential role in cell cycle regulation and cell death.
      Collectively, our findings suggest that NLRP2P is a resurrected processed
      pseudogene that regulates NF-kappaB RelA/p65 activity and thus represents the
      newest member of the POP family, POP4. 

PMID- 24871473
TI  - The plausible health benefits of nuts: associations, causal conclusions, and
      informed decisions.

PMID- 24871474
TI  - Two more pieces to the 1000-piece carbohydrate puzzle.

PMID- 24871475
TI  - Cognition: the new frontier for nuts and berries.
AB  - The inclusion of nuts in the diet is associated with a decreased risk of coronary
      artery disease, hypertension, gallstones, diabetes, cancer, metabolic syndrome,
      and visceral obesity. Frequent consumption of berries seems to be associated with
      improved cardiovascular and cancer outcomes, improved immune function, and
      decreased recurrence of urinary tract infections; the consumption of nuts and
      berries is associated with reduction in oxidative damage, inflammation, vascular
      reactivity, and platelet aggregation, and improvement in immune functions.
      However, only recently have the effects of nut and berry consumption on the
      brain, different neural systems, and cognition been studied. There is growing
      evidence that the synergy and interaction of all of the nutrients and other
      bioactive components in nuts and berries can have a beneficial effect on the
      brain and cognition. Regular nut consumption, berry consumption, or both could
      possibly be used as an adjunctive therapeutic strategy in the treatment and
      prevention of several neurodegenerative diseases and age-related brain
      dysfunction. A number of animal and a growing number of human studies show that
      moderate-duration dietary supplementation with nuts, berry fruit, or both is
      capable of altering cognitive performance in humans, perhaps forestalling or
      reversing the effects of neurodegeneration in aging. 

PMID- 24871476
TI  - Nutritional and health benefits of dried beans.
AB  - Dried beans (often referred to as grain legumes) may contribute to some of the
      health benefits associated with plant-based diets. Beans are rich in a number of
      important micronutrients, including potassium, magnesium, folate, iron, and zinc,
      and are important sources of protein in vegetarian diets. In particular, they are
      among the only plant foods that provide significant amounts of the indispensable
      amino acid lysine. Commonly consumed dried beans are also rich in total and
      soluble fiber as well as in resistant starch, all of which contribute to the low
      glycemic index of these foods. They also provide ample amounts of polyphenols,
      many of which are potent antioxidants. Intervention and prospective research
      suggests that diets that include beans reduce low-density lipoprotein
      cholesterol, favorably affect risk factors for metabolic syndrome, and reduce
      risk of ischemic heart disease and diabetes. The relatively low bean intakes of
      North Americans and northern Europeans can be attributed to a negative culinary
      image as well as to intestinal discomfort attributable to the oligosaccharide
      content of beans. Cooking practices such as sprouting beans, soaking and
      discarding soaking water before cooking, and cooking in water with a more
      alkaline pH can reduce oligosaccharide content. Promotional efforts are needed to
      increase bean intake. 

PMID- 24871478
TI  - Nutritional adequacy of plant-based diets for weight management: observations
      from the NHANES.
AB  - Observational studies have shown that body mass indexes of vegetarians are lower
      than those of nonvegetarians and that caloric intake of vegetarians is typically
      lower than that of nonvegetarians, suggesting that a vegetarian diet could be an
      approach for weight management. However, vegetarians may be at risk of inadequate
      intakes of certain vitamins and minerals. Population-based studies indicate that
      vegetarians have lower mean intakes of vitamin B-12 and zinc and higher intakes
      of fiber, magnesium, and vitamins A, C, and E than do nonvegetarians. Usual
      intake data suggest a similar prevalence of inadequacy between vegetarians and
      nonvegetarians for magnesium and vitamins A, C, and E, with both groups at high
      risk of inadequate intakes of these nutrients. These same data report that
      vegetarians have a higher prevalence of inadequacy for iron, vitamin B-12,
      protein, and zinc than do nonvegetarians. Although mean intake data suggest that
      a vegetarian diet may be a useful approach for weight management, combined with
      energy restriction it may have a detrimental effect on diet quality. Mean intakes
      of fiber, vitamins A and C, magnesium, and iron were significantly lower for
      vegetarians with energy intakes >= 500 kcal below Estimated Energy Requirements
      than for vegetarians who did not restrict energy. Vegetarian diets should be
      recommended for weight management; however, care should be taken to optimize food
      intake to provide adequate intakes of nutrients of concern when energy
      restriction is used in conjunction with a vegetarian dietary pattern. At any
      caloric amount, vegetarians should optimize intakes of vitamin B-12, zinc, and
      protein; and both vegetarians and nonvegetarians need to increase intakes of
      calcium, magnesium, fiber, and vitamins A, C, and E.

PMID- 24871477
TI  - A provegetarian food pattern and reduction in total mortality in the Prevencion
      con Dieta Mediterranea (PREDIMED) study.
AB  - BACKGROUND: Vegetarian diets have been associated with reduced mortality. Because
      a pure vegetarian diet might not easily be embraced by many individuals,
      consuming preferentially plant-derived foods would be a more easily understood
      message. A provegetarian food pattern (FP) emphasizing preference for plant
      derived foods might reduce all-cause mortality. OBJECTIVE: The objective was to
      identify the association between an a priori-defined provegetarian FP and all
      cause mortality. DESIGN: We followed 7216 participants (57% women; mean age: 67
      y) at high cardiovascular risk for a median of 4.8 y. A validated 137-item
      semiquantitative food-frequency questionnaire was administered at baseline and
      yearly thereafter. Fruit, vegetables, nuts, cereals, legumes, olive oil, and
      potatoes were positively weighted. Added animal fats, eggs, fish, dairy products,
      and meats or meat products were negatively weighted. Energy-adjusted quintiles
      were used to assign points to build the provegetarian FP (range: 12-60 points).
      Deaths were confirmed by review of medical records and the National Death Index.
      RESULTS: There were 323 deaths during the follow-up period (76 from
      cardiovascular causes, 130 from cancer, 117 for noncancer, noncardiovascular
      causes). Higher baseline conformity with the provegetarian FP was associated with
      lower mortality (multivariable-adjusted HR for >= 40 compared with <30 points:
      0.59; 95% CI: 0.40, 0.88). Similar results were found with the use of updated
      information on diet (RR: 0.59; 95% CI: 0.39, 0.89). CONCLUSIONS: Among omnivorous
      subjects at high cardiovascular risk, better conformity with an FP that
      emphasized plant-derived foods was associated with a reduced risk of all-cause
      mortality. This trial was registered at www.controlled-trials.com as
      ISRCTN35739639.

PMID- 24871479
TI  - Is iron and zinc nutrition a concern for vegetarian infants and young children in
      industrialized countries?
AB  - Well-planned vegetarian diets are considered adequate for all stages of the life
      cycle, despite limited data on the zinc status of vegetarians during early
      childhood. The bioavailability of iron and zinc in vegetarian diets is poor
      because of their higher content of absorption inhibitors such as phytate and
      polyphenols and the absence of flesh foods. Consequently, children as well as
      adult vegetarians often have lower serum ferritin concentrations than omnivores,
      which is indicative of reduced iron stores, despite comparable intakes of total
      iron; hemoglobin differences are small and rarely associated with anemia.
      However, data on serum zinc concentrations, the recommended biomarker for
      identifying population groups at elevated risk of zinc deficiency, are sparse and
      difficult to interpret because recommended collection and analytic procedures
      have not always been followed. Existing data indicate no differences in serum
      zinc or growth between young vegetarian and omnivorous children, although there
      is some evidence of low serum zinc concentrations in vegetarian adolescents. Some
      vegetarian immigrants from underprivileged households may be predisposed to iron
      and zinc deficiency because of nondietary factors such as chronic inflammation,
      parasitic infections, overweight, and genetic hemoglobin disorders. To reduce the
      risk of deficiency, the content and bioavailability of iron and zinc should be
      enhanced in vegetarian diets by consumption of fortified cereals and milk, by
      consumption of leavened whole grains, by soaking dried legumes before cooking and
      discarding the soaking water, and by replacing tea and coffee at meals with
      vitamin C-rich drinks, fruit, or vegetables. Additional recommended practices
      include using fermented soy foods and sprouting at least some of the legumes
      consumed. Fortified foods can reduce iron deficiency, but whether they can also
      reduce zinc deficiency is less certain. Supplements may be necessary for
      vegetarian children following very restricted vegan diets. 

PMID- 24871481
TI  - Gender specific reproductive strategies of an arctic key species (Boreogadus
      saida) and implications of climate change.
AB  - The Arctic climate is changing at an unprecedented rate. What consequences this
      may have on the Arctic marine ecosystem depends to a large degree on how its
      species will respond both directly to elevated temperatures and more indirectly
      through ecological interactions. But despite an alarming recent warming of the
      Arctic with accompanying sea ice loss, reports evaluating ecological impacts of
      climate change in the Arctic remain sparse. Here, based upon a large-scale field
      study, we present basic new knowledge regarding the life history traits for one
      of the most important species in the entire Arctic, the polar cod (Boreogadus
      saida). Furthermore, by comparing regions of contrasting climatic influence
      (domains), we present evidence as to how its growth and reproductive success is
      impaired in the warmer of the two domains. As the future Arctic is predicted to
      resemble today's Atlantic domains, we forecast changes in growth and life history
      characteristics of polar cod that will lead to alteration of its role as an
      Arctic keystone species. This will in turn affect community dynamics and energy
      transfer in the entire Arctic food chain. 

PMID- 24871482
TI  - An improved technique for removing intramedullary antibiotic beads in
      osteomyelitis of the tibial shaft.
AB  - BACKGROUND: The intramedullary insertion of antibiotic-impregnated cement beads
      is used widely for the treatment of intramedullary infection. This report
      describes an improved technique for removing chains of antibiotic beads inserted
      into the intramedullary cavity. METHODS: We examined four cases in three patients
      of the intramedullary insertion of chains of antibiotic-impregnated cement beads
      for the treatment of osteomyelitis of the diaphysis of the tibia after the
      fixation of fractures with interlocking nails. During bead removal, the tip of an
      intramedullary guidewire was bent into a hook shape and was then engaged with the
      chain of impacted beads. The guidewire was removed from the intramedullary
      cavity, permitting the extraction of any beads adhering to the wire. RESULTS: As
      beads came into contact with the tip of the intramedullary guidewire, they could
      be extracted easily. No additional incision or bone fenestration was required.
      CONCLUSIONS: The use of a hook-shaped intramedullary guidewire simplifies the
      removal of chains of antibiotic-impregnated cement beads without the need for an
      invasive procedure. This technique makes the use of chains of cement beads a
      favorable choice for treating intramedullary infection.

PMID- 24871480
TI  - Molecular dynamics of thermoenzymes at high temperature and pressure: a review.
AB  - Lipases are known for their versatility in addition to their ability to digest
      fat. They can be used for the formulation of detergents, as food ingredients and
      as biocatalysts in many industrial processes. Because conventional enzymes are
      frangible at high temperatures, the replacement of conventional chemical routes
      with biochemical processes that utilize thermostable lipases is vital in the
      industrial setting. Recent theoretical studies on enzymes have provided numerous
      fundamental insights into the structures, folding mechanisms and stabilities of
      these proteins. The studies corroborate the experimental results and provide
      additional information regarding the structures that were determined
      experimentally. In this paper, we review the computational studies that have
      described how temperature affects the structure and dynamics of thermoenzymes,
      including the thermoalkalophilic L1 lipase derived from Bacillus
      stearothermophilus. We will also discuss the potential of using pressure for the
      analysis of the stability of thermoenzymes because high pressure is also
      important for the processing and preservation of foods. 

PMID- 24871483
TI  - Dexamethasone increases Cdc42 expression in human TM-1 cells.
AB  - PURPOSE: Changes in the cytoskeletal organization of the human trabecular
      meshwork (HTM) is thought to be responsible for primary open-angle glaucoma
      (POAG) pathologies. Cdc42 is a Rho GTPase; Rho GTPases are important modulatory
      agents of the cytoskeleton. This study aimed to investigate the effects of
      dexamethasone (DEX) on Cdc42 in a transformed HTM cell line, TM-1 to understand
      the molecular pathologies underlying POAG. METHODS: TM-1 cells were cultured in
      vitro. The cultures were treated with DEX at 10(-6) and 10(-7) M for 1-4 days.
      Cdc42 was silenced using small interfering RNA (siRNA). The expression levels of
      Cdc42 in the TM-1 cells were measured using reverse transcription (RT)-PCR,
      western blotting analysis and immunofluorescence. Its downstream effectors, p21
      activated kinase phosphorylation (phospho-PAK) and myosin light chain kinase
      (MLCK), were measured using western blotting analysis. In addition, the F-actin
      of TM-1 cells was stained using phalloidin. RESULTS: The mRNA and protein levels
      of Cdc42 showed an increase in TM-1 cells with DEX treatment and a decrease in TM
      1 cells transfected with Cdc42 siRNA. Moreover, phospho-PAK levels increased,
      whereas MLCK levels appeared to decrease, with DEX treatment. The F-actin of DEX
      treated TM-1 cells displayed a rearrangement. Cdc42 siRNA decreased the
      expression of Cdc42 and its related proteins, resulting in an attenuation of the
      effects of DEX on Cdc42 and F-actin organization in TM-1 cells. CONCLUSIONS: DEX
      increases Cdc42 expression in TM-1. This may represent a potential mechanism of
      DEX-induced HTM cytoskeletal rearrangement.

PMID- 24871484
TI  - The btp [2,6-bis(1,2,3-triazol-4-yl)pyridine] binding motif: a new versatile
      terdentate ligand for supramolecular and coordination chemistry.
AB  - Ligands containing the btp [2,6-bis(1,2,3-triazol-4-yl)pyridine] motif have
      appeared with increasing regularity over the last decade. This class of ligands,
      formed in a one pot 'click' reaction, has been studied for various purposes, such
      as for generating d and f metal coordination complexes and supramolecular self
      assemblies, and in the formation of dendritic and polymeric networks, etc. This
      review article introduces btp as a novel and highly versatile terdentate building
      block with huge potential in inorganic supramolecular chemistry. We will focus on
      the coordination chemistry of btp ligands with a wide range of metals, and how it
      compares with other classical pyridyl and polypyridyl based ligands, and then
      present a selection of applications including use in catalysis, enzyme
      inhibition, photochemistry, molecular logic and materials, e.g. polymers,
      dendrimers and gels. The photovoltaic potential of triazolium derivatives of btp
      and its interactions with anions will also be discussed.

PMID- 24871486
TI  - Molecular diversity in phenolic and polyphenolic precursors of tannin-inspired
      nanocoatings.
AB  - The strong interfacial properties of selected plant polyphenols were recently
      exploited in forming functionally versatile nanocoatings via dip-coating. Here,
      we screened a library of ~20 natural and synthetic phenols and polyphenols,
      identifying eight catechol-, gallol- and resorcinol-rich precursors capable of
      forming coatings. Several newly identified compounds expand the molecular
      diversity of tannin-inspired coatings.

PMID- 24871485
TI  - Association between the organoleptic scores, oral condition and salivary beta
      galactosidases in children affected by halitosis.
AB  - OBJECTIVES: The goal of this work is to evaluate the association between
      organoleptic scores, oral condition and salivary beta-galactosidases, to
      facilitate the differential diagnosis of halitosis in children. METHODS: Fifty
      systemically healthy children with a primary complaint of oral malodour were
      included in this cross-sectional study. The organoleptic evaluation was carried
      out by two judges, evaluating the intensity of malodour of the air exhaled 5 s
      through the mouth of the patients, at a distance of approximately 10 cm from
      their noses; the level of salivary beta-galactosidases was quantified
      spectrophotometrically after a chromatic reaction between a salivary sample of
      each patient and a specific chromatic substrate of the enzyme. Clinical
      conditions, such as visible plaque and gingival bleeding index, tongue coating
      score, localized food stagnation and other oral parameters, were evaluated by
      qualified dentists through an oral check-up. RESULTS: The beta-galactosidase
      level was significantly related to the organoleptic scores and clinical
      parameters, such as the tongue coating score and the visible plaque index.
      Stratifying results with respect to the different phase of the day at which
      parents complained halitosis in their children, statistical analysis showed that
      the organoleptic scores and the level of beta-galactosidases were significantly
      higher in children who suffered of halitosis during the whole day, A = 40%, with
      respect to those without this problem, N = 20% (P = 0.001 and P = 0.006,
      respectively). CONCLUSIONS: Certain oral parameters such as halitosis during the
      whole day, high tongue coating score and high visible plaque index were
      particularly associated with an increase in the salivary beta-galactosidase
      level.

PMID- 24871487
TI  - Giardia lamblia binding immunoglobulin protein triggers maturation of dendritic
      cells via activation of TLR4-MyD88-p38 and ERK1/2 MAPKs.
AB  - Much remains unknown about the mammalian immune response to Giardia lamblia, a
      protozoan pathogen that causes diarrhoeal outbreaks. We fractionated protein
      extracts of G. lamblia trophozoites by Viva-spin centrifugation, DEAE ion
      exchange and gel filtration chromatography. Resultant fractions were screened for
      antigenic molecules by western blots analysis using anti-G. lamblia antibodies
      (Abs), resulting in identification of G. lamblia binding immunoglobulin protein
      (GlBiP). Maturation of mouse dendritic cells (DCs) in response to recombinant
      GlBiP (rGlBiP) was detected by increased expression of surface molecules such as
      CD80, CD86 and MHC class II; these mature DCs, produced pro-inflammatory
      cytokines (TNF-alpha, IL-12 and IL-6). Especially, the truncated rGlBiP
      containing the heat-shock protein 70 domain-induced cytokine production from
      mouse DCs. rGlBiP-induced DC activation was initiated by TLR4 in a MyD88
      dependent way and occurred through activation of p38 and ERK1/2 MAPKs as well as
      increased activity of NF-kappaB and AP-1. Moreover, CD4(+) T cells stimulated
      with rGlBiP-treated DCs produced high levels of IL-2 and IFN-gamma. Together, our
      results suggest that GlBiP contributes to maturation of DCs via activation of
      TLR4-MyD88-p38, ERK1/2 MAPK, NF-kappaB and AP-1.

PMID- 24871488
TI  - Cheese 'refinement' with whey B-vitamin removal during precipitation potentially
      induces temporal 'functional' dietary shortage: homocysteine as a biomarker.
AB  - Cottage cheese 'refinement' with massive B-vitamin losses (~70-84%) through whey
      removal during precipitation may potentially induce an acute imbalance between
      protein/methionine load and temporal inadequacy/shortage of nutrients critical
      for their metabolism, i.e. B6 and B12. The temporal effect of cottage cheese
      consumption was evaluated using increased plasma homocysteine as a B-vitamin
      shortage marker. In a double-blind study, healthy, normal-weight (BMI = 22-27),
      premenopausal women aged 25-45 years were first given a methionine load (100 mg
      kg(-1), n = 15), then cottage cheese alone (500 g, ~50 g protein, ~1200 mg
      methionine, n = 49) at breakfast, and then with added B6 (2 mg, n = 8) and/or B6
      + folate (1 mg + 200 mcg, n = 7). Plasma homocysteine was measured preprandially
      (t0) and then postprandially 5 h (t5) and >=6-24 h. Cheese-induced homocysteine
      increased 28.7% (p <= 0.001), ~60% of the free methionine response, remaining
      higher through >=6-8 h. Co-supplementation with B6 reduced the Hcy increase by
      45.0% (to 14.9%, p = 0.025), and that with B6 + folate reduced the Hcy increase
      by 72.3% (to 7.5%, p = 0.556, NS). Homocysteine increased more in participants
      with lower baselines (<5 MUM vs. >=5 MUM, p <= 0.001) following cheese, ~3-fold
      (54.8% vs. 18.5%) or methionine, 47.3% (266.7% vs. 181.1%). Cheese B-vitamin
      depletion - i.e. to B6 ~ 2.0-4.0 MUg g(-1) protein, far below women's metabolic
      requirement (15-20 MUg g(-1)) - appeared to induce acute relative shortage
      compared to methionine/protein loads, exemplified by greater homocysteine
      increases than with other animal proteins (previous data), more so with lower
      baseline homocysteine. Smaller increases following re-supplementation
      demonstrated potential for 'functional fortification'/co-supplementation. Unnoted
      cheese 'refinement', like white bread, potentially induces episodic vitamin
      shortage effects, warranting consideration for acute/cumulative implications,
      alternative processing/supplementation technologies, and food combinations,
      especially for at-risk populations (i.e. with genetic, hormonal/gender, or aging
      related predispositions), and for cardiovascular, bone, and brain health. 

PMID- 24871490
TI  - Animal density and track counts: understanding the nature of observations based
      on animal movements.
AB  - Counting animals to estimate their population sizes is often essential for their
      management and conservation. Since practitioners frequently rely on indirect
      observations of animals, it is important to better understand the relationship
      between such indirect indices and animal abundance. The Formozov-Malyshev
      Pereleshin (FMP) formula provides a theoretical foundation for understanding the
      relationship between animal track counts and the true density of species.
      Although this analytical method potentially has universal applicability wherever
      animals are readily detectable by their tracks, it has long been unique to Russia
      and remains widely underappreciated. In this paper, we provide a test of the FMP
      formula by isolating the influence of animal travel path tortuosity (i.e.,
      convolutedness) on track counts. We employed simulations using virtual and
      empirical data, in addition to a field test comparing FMP estimates with
      independent estimates from line transect distance sampling. We verify that track
      counts (total intersections between animals and transects) are determined
      entirely by density and daily movement distances. Hence, the FMP estimator is
      theoretically robust against potential biases from specific shapes or patterns of
      animal movement paths if transects are randomly situated with respect to those
      movements (i.e., the transects do not influence animals' movements). However,
      detectability (the detection probability of individual animals) is not determined
      simply by daily travel distance but also by tortuosity, so ensuring that all
      intersections with transects are counted regardless of the number of individual
      animals that made them becomes critical for an accurate density estimate.
      Additionally, although tortuosity has no bearing on mean track encounter rates,
      it does affect encounter rate variance and therefore estimate precision. We
      discuss how these fundamental principles made explicit by the FMP formula have
      widespread implications for methods of assessing animal abundance that rely on
      indirect observations. 

PMID- 24871493
TI  - Nutrition Interventions to Optimize Pediatric Wound Healing: An Evidence-Based
      Clinical Pathway.
AB  - Background and Objective: There is no accepted nutrition approach for wound
      healing in children. Our aims were to determine optimal nutrition support for
      pediatric wound healing. Methods: We applied local methods to create evidence-
      and consensus-based recommendations, supported by implementation tools, including
      algorithms, clinical decision supports, and measures. We applied these
      recommendations to the care of 49 patients from December 5, 2011, to December 5,
      2012. Results: Six articles were found that addressed our clinical questions, and
      we formulated 5 clinical recommendations. Evidence supported evaluating patients
      for vitamin C, zinc, and protein deficiency. Of the patients where laboratory
      values were checked, 9 patients were zinc deficient (33%) and 12 patients were
      vitamin C deficient (48%). Discussion and Practical Application: The
      implementation of our recommendations has led to increased identification of
      micronutrient deficiencies and closer monitoring of nutrition status and intake.
      Online clinical decision supports can accelerate the adoption of clinical
      recommendations and reduce provider practice variation.

PMID- 24871489
TI  - Predicting Future Suicide Attempts Among Adolescent and Emerging Adult
      Psychiatric Emergency Patients.
AB  - The purpose of this study was to longitudinally examine specific characteristics
      of suicidal ideation in combination with histories of suicide attempts and non
      suicidal self-injury (NSSI) to best evaluate risk for a future attempt among high
      risk adolescents and emerging adults. Participants in this retrospective medical
      record review study were 473 (53% female; 69% Caucasian) consecutive patients,
      ages 15 to 24 years (M=19.4 years) who presented for psychiatric emergency
      services during a 9-month period. These patients' medical records, including a
      clinician-administered Columbia-Suicide Severity Rating Scale, were coded at the
      index visit and at future visits occurring within the next 18 months. Logistic
      regression models were used to predict suicide attempts during this period.
      Socioeconomic status, suicidal ideation severity (i.e., intent, method), suicidal
      ideation intensity (i.e., frequency, controllability), a lifetime history of
      suicide attempt, and a lifetime history of NSSI were significant independent
      predictors of a future suicide attempt. Suicidal ideation added incremental
      validity to the prediction of future suicide attempts above and beyond the
      influence of a past suicide attempt, whereas a lifetime history of NSSI did not.
      Sex moderated the relationship between the duration of suicidal thoughts and
      future attempts (predictive for male patients but not female). Results suggest
      value in incorporating both past behaviors and current thoughts into suicide risk
      formulation. Furthermore, suicidal ideation duration warrants additional
      examination as a potential critical factor for screening assessments evaluating
      suicide risk among high-risk samples, particularly for male patients.

PMID- 24871492
TI  - The Experiences of Patients With Advanced Head and Neck Cancer With a
      Percutaneous Endoscopic Gastrostomy Tube: A Qualitative Descriptive Study.
AB  - Background: While the percutaneous endoscopic gastrostomy (PEG) tube has become
      an established part of the management regimen for patients with head and neck
      cancer (HNCA) with impaired nutrition and functional status, limited research has
      explored the impact and experiences of living with a PEG tube from the patient's
      perspective. This qualitative study serves as a follow-up investigation
      undertaken to describe the experiences of patients with advanced HNCA living with
      a PEG tube. Materials and Methods: Eligible patients from convenience sampling
      were invited to participate until data saturation was reached. In-depth
      interviews were conducted with consenting participants. Qualitative descriptive
      design guided the content analysis of the interview transcripts. Results: Of the
      49 patients invited, a total of 15 participants' interviews were transcribed and
      analyzed. Each interview was 15-90 minutes in length. Four of 22 content codes
      were chosen to describe the overarching ideas of the progressive experience of a
      patient's journey from the initial decision-making process around tube insertion
      through to its removal. Difficulty swallowing and weight loss emerged as primary
      factors for PEG tube insertion, and all participants became accustomed to living
      with the tube. Resuming a complete oral diet was a gradual transition. All
      participants recognized the value of the tube, and most acknowledged its
      necessity for their survival. Conclusions: Results describe the overall PEG tube
      experience as a dichotomy. While there were issues with the PEG tube, all
      participants found the tube to be beneficial. This study provides invaluable
      insight from a practice perspective.

PMID- 24871495
TI  - Survival after major cardiac surgery: performance and comparison of predictive
      ability of EuroSCORE II and logistic EuroSCORE in a sample of Mediterranean
      population.
AB  - BACKGROUND: The European System for Cardiac Operative Risk Evaluation (EuroSCORE)
      II has been recently introduced to improve mortality prediction in cardiac
      surgery. We compare the predictive ability of the new EuroSCORE II with that of
      the original logistic EuroSCORE and we made an evaluation of a sample of our
      population submitted to major cardiac surgery in the context of a Mediterranean
      country. MATERIALS AND METHODS: Predicted and observed mortality were recorded in
      1,200 consecutive patients undergoing major cardiac surgery at our institution
      with both logistic EuroSCORE and EuroSCORE II. Patients were grouped according to
      type of surgery: isolated valvular (n = 538), isolated coronary (n = 322),
      combined (n = 192), and miscellaneous (n = 148). Predictive capacity of both
      scales was compared for overall population and for each group in terms of
      calibration and discrimination using the observed by expected mortality rate,
      Hosmer-Lemeshow test, and C-statistic. RESULTS: Overall mortality was 6.8%,
      whereas that predicted by logistic EuroSCORE and EuroSCORE II was 9.7 and 3.7%,
      respectively. Mortality in our population was higher than mortality expected
      according to the original EuroSCORE II database. For all groups included in our
      population, logistic EuroSCORE overestimated mortality and EuroSCORE II
      underestimated the outcome even more. However, EuroSCORE II showed better
      calibration than logistic EuroSCORE for overall, valvular, and combined surgery.
      In contrast, logistic EuroSCORE demonstrated better calibration for coronary
      surgery. Discrimination capacity was good for both risk scores, but it was
      superior for logistic EuroSCORE than for EuroSCORE II in all considered subgroups
      unless combined surgery. CONCLUSION: Mortality in our population was higher than
      the mortality that would have been expected by the new EuroSCORE II analysis.
      Although EuroSCORE II has good calibration and discrimination capacity, both are
      worse than those demonstrated by logistic EuroSCORE. Forthcoming evaluations are
      necessary when the new model will be widely used.

PMID- 24871496
TI  - Emissions from an international airport increase particle number concentrations 4
      fold at 10 km downwind.
AB  - We measured the spatial pattern of particle number (PN) concentrations downwind
      from the Los Angeles International Airport (LAX) with an instrumented vehicle
      that enabled us to cover larger areas than allowed by traditional stationary
      measurements. LAX emissions adversely impacted air quality much farther than
      reported in previous airport studies. We measured at least a 2-fold increase in
      PN concentrations over unimpacted baseline PN concentrations during most hours of
      the day in an area of about 60 km(2) that extended to 16 km (10 miles) downwind
      and a 4- to 5-fold increase to 8-10 km (5-6 miles) downwind. Locations of maximum
      PN concentrations were aligned to eastern, downwind jet trajectories during
      prevailing westerly winds and to 8 km downwind concentrations exceeded 75 000
      particles/cm(3), more than the average freeway PN concentration in Los Angeles.
      During infrequent northerly winds, the impact area remained large but shifted to
      south of the airport. The freeway length that would cause an impact equivalent to
      that measured in this study (i.e., PN concentration increases weighted by the
      area impacted) was estimated to be 280-790 km. The total freeway length in Los
      Angeles is 1500 km. These results suggest that airport emissions are a major
      source of PN in Los Angeles that are of the same general magnitude as the entire
      urban freeway network. They also indicate that the air quality impact areas of
      major airports may have been seriously underestimated. 

PMID- 24871497
TI  - Comment on "Pain in people living with HIV/AIDS: a systematic review (Parker et
      al. 2014)".

PMID- 24871498
TI  - Response to comment on "Pain in people living with HIV/AIDS: a systematic review
      (Parker et al. 2014)".

PMID- 24871499
TI  - Pelvic mass after prostatectomy. Pseudosarcomatous fibromyxoid tumor.

PMID- 24871502
TI  - Clinical significance of monitoring perfusion in non-vital organs.

PMID- 24871500
TI  - Tigecycline use in critically ill patients: a multicentre prospective
      observational study in the intensive care setting.
AB  - PURPOSE: This prospective observational study aimed at describing prescription
      patterns of tigecycline and patient outcomes in 26 French intensive care units
      (ICU). METHODS: Data of consecutive cases of adult patients treated with
      tigecycline were collected from the initiation until 7 days after the end of
      treatment. Response to treatment was classified as success, failure or
      undetermined and analyses were presented according to severity (SOFA score <7 or
      >=7). Survival was recorded at 28 days. RESULTS: A total of 156 patients were
      included (64% male, age 60 +/- 15 years). At inclusion, 53% had a SOFA score >=7;
      93% had received prior anti-infective agents. Tigecycline was given as first-line
      treatment in 47% of patients, mostly in combination (67%), for intra-abdominal
      (IAI 56%), skin and soft tissue (SSTI 19%) or other infections. A total of 76% of
      the treated infections were hospital-acquired. Bacteraemia was reported in 12% of
      patients. Median treatment duration was 9 days. Tigecycline was prematurely
      stopped in 42% patients. The global success rate was 60% at the end of treatment,
      and significantly higher with treatment duration more than 9 days (76 vs. 47%, P
      < 0.001). Success rate was 65% for patients alive at the end of treatment.
      Success rates tended to decrease with illness severity, immunosuppression,
      bacteraemia and obesity. Survival rate at day 28 was 85% in the whole cohort and
      significantly higher in the less severely ill patients (P < 0.001). CONCLUSIONS:
      Tigecycline success rates appear comparable to those reported in clinical studies
      in ICU with severe infections. Tigecycline could be an alternative in ICU
      patients.

PMID- 24871503
TI  - The first morphological description of the immature stages of Thiasophila Kraatz,
      1856 (Coleoptera; Staphylinidae) inhabiting ant colonies of the Formica rufa
      group.
AB  - This article for the first time presents the morphology of the egg, three larval
      instars, pupal cocoon, prepupa and pupa of myrmecophilous rove beetle Thiasophila
      angulata (Erichson, 1837) along with illustrations of structural features and
      chaetotaxy. Morphological comparisons are made between larval instars, and
      between the mature larva of T. angulata and other known larvae of Aleocharinae
      belonging to the tribes Athetini, Hoplandriini, Liparocephalini, Lomechusinii and
      Oxypodini. Pupae of T. angulata and two other species of Aleocharinae: Pella
      laticollis (Markell, 1844) and Haploglossa picipennis (Gyllenhal, 1827) are
      compared. The mature larvae of T. angulata were observed to vary morphologically
      depending on the ant host species (Formica polyctena, F. rufa or F. truncorum).
      Host-related variation was observed in median larval body length, head and
      pronotum width and structure of the antennae. 

PMID- 24871501
TI  - Is there a future for tigecycline?

PMID- 24871504
TI  - New species of earthworms belonging to the Metaphire formosae species group
      (Clitellata: Megascolecidae) in Taiwan.
AB  - The Metaphire formosae species group is a member of the Pheretima complex of the
      family Megascolecidae. It is composed of 12 nominal taxa, Metaphire bununa Tsai
      et al., 2000, Metaphire feijani Chang & Chen, 2004, Metaphire formosae
      (Michaelsen, 1922), Metaphire glareosa Tsai et al., 2000, Metaphire nanaoensis
      Chang & Chen, 2005, Metaphire paiwanna paiwanna Tsai et al., 2000, Metaphire
      paiwanna hengchunensis (James et al., 2005), Metaphire paiwanna liliumfordi Tsai
      et al., 2000, Metaphire tahanmonta Chang & Chen, 2005, Metaphire taiwanensis Tsai
      et al., 2004, Metaphire trutina Tsai et al., 2003, and Metaphire yuhsi (Tsai,
      1964). In this study, we describe a new species, Metaphire tengjhihensis sp.
      nov., and two new subspecies, Metaphire nanaoensis truku ssp. nov. and Metaphire
      taiwanensis tsaii ssp. nov., belonging to this species group. DNA barcodes
      (partial sequences of the mitochondrial cytochrome c oxidase subunit 1, COI) from
      type specimens of M. feijani, M. tengjhihensis sp. nov., M. nanaoensis truku ssp.
      nov., M. tahanmonta and M. taiwanensis tsaii ssp. nov. have been deposited in
      GenBank in previous studies and are explicitly linked to the type specimens for
      the first time, enabling unambiguous identification using both morphology and DNA
      barcodes. Finally, we comment on the systematics of the M. formosae species group
      and suggest an integrative taxonomic approach that combines morphology and DNA
      barcodes for future descriptions of new species of Amynthas and Metaphire.

PMID- 24871505
TI  - Review of the leafhopper genus Singapora Mahmood (Hemiptera: Cicadellidae:
      Typhlocybinae: Erythroneurini).
AB  - General characteristics of Singapora Dworakowska and a key to known species of
      the genus are provided. Six new species, Singapora candela, S. excedens, S.
      falcata, S. longiantrosa, S. triacantha and S. yingjiangica spp. nov. are
      described and illustrated, with two new records, S. shivae Dworakowska from China
      and S. bannaensis Song & Li from Thailand. 

PMID- 24871506
TI  - Two new feather mite species of the family Pteronyssidae (Acarina: Analgoidea)
      from Meghalaya (Northeast India).
AB  - Two new species of the feather mite family Pteronyssidae (Acariformes:
      Analgoidea) from passerines of the families Leiothrichidae and Pycnonotidae in
      India (Meghalaya, East Jaintia Hills District) are described: Timalinyssus
      actinodurae Constantinescu sp. nov. from Actinodura cyanouroptera (Hodgson)
      (Leiothrichidae) and Pteroherpus meghalayensis Constantinescu sp. nov. from
      Hemixos flavala Blyth (Pycnonotidae). Timalinyssus actinodurae differs from all
      of the other species of the genus due to a particular shape of the opisthosomal
      lobes in both sexes and having a strong sclerotised band in postero-median area
      of the hysteronotal shield in male. The male of Pteroherpus meghalayensis differs
      due to a very long genital apparatus and unusual length of the tips of epiandrum
      that extend the level of the genital apparatus.

PMID- 24871507
TI  - Water mites from caves of the Ha Giang province, northern Vietnam (Acari:
      Hydrachnidia).
AB  - Four species of water mites (Acari, Hydrachnidia) were collected in 2010 during
      an Italian speleological expedition to caves of the Ha Giang region in northern
      Vietnam from rimstone pools or other tiny accumulations of percolating water.
      Four taxa new to science are described, representing the families Torrenticolidae
      (Torrenticola anophthalma nov. sp., Stygotorrenticola coniseta nov. gen., nov.
      sp.), Limnesiidae (Raptorhydracarinae subfam. nov., Raptorhydracarus tomasini
      nov. gen., nov sp.) and Athienemanniidae (Africasia vietnamitica sp. nov.). Most
      of these taxa show striking morphological adaptations to subterranean life. 

PMID- 24871508
TI  - Cyrts in the city: a new Bent-toed Gecko (Genus Cyrtodactylus) is the only
      endemic species of vertebrate from Batu Caves, Selangor, Peninsular Malaysia.
AB  - Cyrtodactylus metropolis sp. nov. from Batu Caves massif, Selangor, Peninsular
      Malaysia is differentiated from all congeners by having a unique suite of
      morphological and color pattern characteristics. Remarkably, this species has
      been overlooked despite a plethora of field studies at Batu Caves from 1898 to
      the present and no specimens had ever been examined until now. As with all other
      limestone forest-adapted Cyrtodactylus in Peninsular Malaysia, C. metropolis sp.
      nov. is not a cave-adapted species but is far more common on the exterior
      surfaces of the Batu Caves limestone massif and its surrounding limestone
      vegetation. We suggest that researchers devote time exploring the exterior
      surfaces of limestone massifs as well the interiors of their caves. 

PMID- 24871509
TI  - A new genus and species of Mirini from Argentina (Hemiptera: Heteroptera:
      Miridae).
AB  - Mendozamiris chiquillanes is described as a new genus and species from Mendoza,
      Malargue Department, Argentina. 

PMID- 24871510
TI  - A preliminary study of the genus Nymphicula Snellen from Australia, New Guinea
      and the south Pacific (Lepidoptera: Pyraloidea: Crambidae: Acentropinae).
AB  - The species of Nymphicula occurring in Australia and south Pacific islands are
      described and illustrated. 22 new species are described: N. adelphalis, N.
      christinae, N. conjunctalis, N. edwardsi, N. hampsoni, N. ochrepunctalis, N.
      torresalis, N. beni, N. irianalis, N. michaeli, N. monticola, N. nokensis, N.
      plumbilinealis, N. submarginalis, N. susannae, N. tariensis, N. xanthocostalis,
      N. fionae, N. insulalis, N. lactealis, N. lifuensis, N. cheesmanae. A replacement
      name is proposed for Cataclysta dialitha Tams: Nymphicula samoensis. 

PMID- 24871511
TI  - Dulichiella celestun, a new species of amphipod (Crustacea: Amphipoda: Melitidae)
      from the Gulf of Mexico, with a key and zoogeographic remarks for the genus in
      the western Atlantic.
AB  - The discovery of a new melitid amphipod in the Celestun Biosphere Reserve
      (northern Yucatan peninsula, SE Gulf of Mexico) is reported. Dulichiella celestun
      sp. nov. differs from its congeners by an unique set of characteristics:
      truncated lateral cephalic lobe, mandibular palp article 1 having inner margin
      produced distally, carpus longer than the propodus of gnathopod 1, gnathopod 2
      propodus distolateral crown with four spines, pereopods 3-7 dactylar unguis
      anterior margin with two accessory spines, and urosomite 3 bearing four dorsal
      spines. A key to species and zoogeographical affinities among members of the
      genus in the western Atlantic are also provided. 

PMID- 24871512
TI  - Proposition of a new species group in Edessa Fabricius, 1803 (Hemiptera:
      Heteroptera: Pentatomidae: Edessinae).
AB  - The pudibunda group of Edessa is here proposed to include Edessa pudibunda Stal,
      1862, Edessa picticornis Stal, 1872, Edessa godmani Distant, 1881, Edessa
      punctata Santos & Fernandes sp. nov., Edessa luteomaculata Santos & Fernandes sp.
      nov., Edessa nigriventris Santos & Fernandes sp. nov. and Edessa nigridorsata sp.
      nov. This group is restricted to Central America. Descriptions, measurements and
      illustrations of the metasternal process, male and female external genitalia and
      distributional map are provided. Lectotypes of E. godmani and E. picticornis are
      here designated. 

PMID- 24871513
TI  - Three new species of Coccobius Ratzeburg (Hymenoptera, Aphelinidae) and
      redescription of C. abdominis Huang and C. furviflagellatus Huang from China.
AB  - Three new species of Coccobius Ratzeburg (Hymenoptera: Aphelinidae) are described
      from China, Coccobius bimaculatus Wang, Huang & Polaszek sp. nov., Coccobius
      jinshanensis Wang, Huang & Polaszek sp. nov. and Coccobius leptocerus Wang, Huang
      & Polaszek sp. nov. Coccobius abdominis Huang 1994 and Coccobius furviflagellatus
      Huang 1994, originally described in Chinese, are redescribed in English and
      illustrated by macrophotography based on newly collected material. All five
      species were reared from Diaspididae (Hemiptera) scale insects on bamboo. Both
      the male of C. furviflagellatus and the diaspidid host association of C.
      abdominis and C. furviflagellatus are recorded for the first time. 

PMID- 24871514
TI  - Two new species of the Simulium batoense species-group of Simulium
      (Gomphostilbia) (Diptera: Simuliidae) from Peninsular Malaysia.
AB  - Two new black fly species, Simulium (Gomphostilbia) tekamense and Simulium
      (Gomphostilbia) jerantutense, are described based on adult females emerged from
      pupae in Peninsular Malaysia, and assigned to the binuanense subgroup of the
      batoense species-group in the subgenus Gomphostilbia. Simulium (G.) tekamense sp.
      nov. is characterized in the female by the subcosta with 0-2 hairs, and presence
      of a  deep notch on the apex of the mediolongitudinal ridge of the cibarium, and
      in the pupa by one of two paired gill filaments of the middle triplet much
      thicker than the counter filament. Simulium (G.) jerantutense sp. nov. is
      characterized in the female by the short claw tooth 0.46 times the length of the
      claw, and in the pupa by the gill filaments arranged as [2+1+(1+2)]+2 filaments
      from dorsal to ventral. Taxonomic notes are given to distinguish these new
      species from related species. 

PMID- 24871515
TI  - Two new dwarfgobies of the genus Eviota from the Ryukyu Islands, Japan
      (Teleostei: Gobiidae).
AB  - Two species of dwarfgoby are described from the Ryukyu Islands, Japan. Eviota
      flebilis n. sp. belongs to cephalic sensory-pore system pattern 2 (lacking only
      IT pore), has a dorsal/anal fin-ray formula of 8/7, unbranched pectoral-fin rays,
      the 5th pelvic-fin ray 12.9% of the 4th, a distinctive narrow, red-orange line
      under the eye, and a dark vertical line at the caudal-fin base. Eviota specca n.
      sp. has a cephalic sensory-pore system pattern 1 (complete), has a dorsal/anal
      fin formula of 8/8, the body heavily sprinkled with chromatophores, and a single
      dark spot on the upper pectoral-fin base.

PMID- 24871516
TI  - A new species of Epania Pascoe (Coleoptera: Cerambycidae: Cerambycinae:
      Molorchini) from Papua New Guinea.
AB  - A new species, Epania gressitti sp. nov., is described. Specimens were
      intercepted from imported ebony timber (Diospyros sp., Ebenaceae) from Papua New
      Guinea. A key to Epania species in Papua New Guinea is presented. 

PMID- 24871517
TI  - Taxonomic notes on Ochlerus: revisiting Herrich-Schaffer's species (Hemiptera:
      Pentatomidae: Discocephalinae: Ochlerini).
AB  - The status of the three species of Ochlerus Spinola, 1837, described by Herrich
      Schaffer in 1844 is reviewed. Ochlerus coriaceus and O. lutosus are removed from
      the synonymy of O. cinctus Spinola, 1837, while O. sordidus is transferred to
      Paralincus sordidus. Lectotypes are designated, and photos for each type and new
      records for O. coriaceus are provided. 

PMID- 24871518
TI  - The family Diaphanidae (Gastropoda: Heterobranchia: Cephalaspidea) in Europe,
      with a redescription of the enigmatic species Colobocephalus costellatus M. Sars,
      1870.
AB  - Diaphanidae has traditionally been considered the basal family of the
      heterobranch gastropod clade Cephalaspidea with 14 species present in Europe
      ascribed to five genera. The monophyletic status of the family is controversial
      because of lack of sound synapomorphies. In this paper we present a review of the
      diversity of Diaphanidae in Europe and give new data on the morphology and
      anatomy of 50% of the species together with a synopsis of the relevant systematic
      characters to distinguish between all European species and genera. The rare
      species Colobocephalus costellatus is redescribed and shown alive for the first
      time.Further evidence supporting the non-monophyly of Diaphanidae is given; no
      synapomorphies were found to unite traditional Diaphanidae taxa, but three groups
      can be recognized: (1) Diaphaninae with genus Diaphana is united by a globose
      external, thin, and umbilicate shell and radulae with a bilobed rachidian tooth;
      (2) Toledoniinae, with genera Toledonia and Bogasonia share the presence of a
      shell with elevated spire and radulae with a unicuspid rachidian tooth; and (3)
      an unnamed group, with Colobocephalus and Colpodaspis which are the only genera
      with internal shells, sculptured and globose with short but protruding spires,
      and radulae lacking rachidian tooth and with smooth hook-shaped lateral teeth. 

PMID- 24871519
TI  - Notes on Lycocerus kiontochananus (Pic, 1921) and description of two new species
      of Lycocerus Gorham from China (Coleoptera, Cantharidae).
AB  - The Lycocerus kiontochananus species complex is revised; L. perroudi (Pic, 1937)
      stat. rev., originally in Cantharis, is resurrected from synonymy with L.
      kiontochananus (Pic, 1921); L. atropygidialis (Pic, 1937) stat. nov., originally
      in Cantharis, is upgraded from Cantharis perroudi var. atropygidialis Pic, 1937
      and resurrected from synonymy with L. kiontochananus; L. kejvali Svihla, 2004
      syn. nov. is considered as a junior synonym with L. kiontochananus. The male of
      L. perroudi and the female of L. jendeki Svihla, 2005 are described for the first
      time. Two new species are described under the names of L. metalliceps sp. nov.
      (China: Sichuan) and L. hainanus sp. nov. (China: Hainan). 

PMID- 24871520
TI  - Species of the subgenus Cantotrella (Orthoptera: Gryllidae: Podoscirtinae:
      Varitrella) from Singapore, Malaysia and Indonesia.
AB  - Ten species of the subgenus Cantotrella Gorochov, 2006 belonging to the genus
      Varitrella Gorochov, 2003 of the tribe Podoscirtini are recorded from Singapore,
      Malaysia and Indonesia. Eight of them are new and described here: V. (C.) orion
      sp. nov.; V. (C.) trusmadi sp. nov.; V. (C.) striata sp. nov.; V. (C.) robusta
      sp. nov., V. (C.) sukau sp. nov., V. (C.) tawau sp. nov., V. (C.) amoena sp.
      nov., V. (C.) manukan sp. nov. 

PMID- 24871521
TI  - Redescription of Odontozona edwardsi (Bouvier, 1908) (Decapoda: Stenopodidea:
      Stenopodidae) and description of a new species of Odontozona commensal on the
      deep-water coral, Lophelia pertusa (Linneaus, 1758).
AB  - Odontozona edwardsi, a rare stenopodid shrimp from deep waters of the northwest
      African coast off Morocco and Western Sahara is redescribed and figured based on
      type material and an additional 26 specimens including some from the Gulf of
      Cadiz and off Roscoff, France. Specimens of another Odontozona from the Gulf of
      Mexico, off Sapelo Island, Georgia, and off Rio de Janeiro, Brazil have been
      confused with O. edwardsi and O. spongicola. This Odontozona is associated with
      the deep sea hard coral Lophelia pertusa and is herewith designated as a new
      species. Both these Atlantic species of Odontozona are distinguished from the
      deep-water Pacific O. spongicola as well as the recently described southwestern
      Atlantic O. meloi by several morphological characters. A key to the Atlantic
      species of Odontozona is presented. 

PMID- 24871522
TI  - Two new species of Amemboa Esaki (Heteroptera: Gerridae) from West Bengal, India.
AB  - Amemboa mahananda sp. nov. and Amemboa bifurcata sp. nov. are described from
      Mahananda Wildlife Sanctuary, in the Darjeeling district and from Kalikhola, in
      the Jalpaiguri district of West Bengal, and compared with all allied species. A
      species checklist of the genus Amemboa Esaki, 1925  and Amemboides Polhemus &
      Andersen, 1984 from India and their distribution in India and elsewhere is
      provided. Amemboa kumari (Distant, 1910) is reported for the first time from West
      Bengal and Amemboa dentata Polhemus & Andersen, 1984 is newly recorded from
      Himachal Pradesh. 

PMID- 24871523
TI  - Spiders of the genus Utivarachna from China (Araneae: Corinnidae).
AB  - The spiders of the genus Utivarachna from China are reviewed. These species
      belong to the kinabaluensis species group. A total of five species are reported
      including three new species, Utivarachna arcuata sp. nov., Utivarachna fabaria
      sp. nov. and Utivarachna gongshanensis sp. nov. Descriptions of the new species
      and the differences between the new species and their related taxa in China are
      discussed. 

PMID- 24871524
TI  - Second species of Augochlorodes (Hymenoptera: Halictidae: Augochlorini) with
      known males and first record for the genus in Argentina.
AB  - The bee genus Augochlorodes Moure, up to now only known from Brazil, is recorded
      for the first time for Argentina. Augochlorodes politus Goncalves & Melo was
      found in the south of the province of Buenos Aires, mideastern Argentina, being
      the southernmost record for the genus. The female of A. politus is redescribed
      and the male described for the first time, being the second male known for this
      genus. The phylogenetic position of Augochlorodes among Augochlorini is briefly
      discussed. 

PMID- 24871525
TI  - Megadrymus brigalow n.sp. (Insecta: Hemiptera: Heteroptera: Rhyparochromidae:
      Drymini), a diminutive new species of seed bug from semi-evergreen vine thicket
      of the Queensland Brigalow Belt.
AB  - Megadrymus brigalow n. sp., a new species of seed bug, is described from semi
      evergreen vine thicket in the Brigalow Belt region of Queensland, Australia. This
      species has the smallest body in the genus Megadrymus Gross and has a number of
      vestigial characters. 

PMID- 24871526
TI  - Surgical approach to the palpable undescended testis.
AB  - An undescended testis may be associated with abnormal testicular development and
      function. A number of testes that are undescended at birth have been observed to
      descend spontaneously. The goal of orchidopexy remains to place those testes in
      the scrotum that would not have descended spontaneously. How long should the
      surgeon wait for spontaneous descent? By what age should the testis be positioned
      in the scrotum to avert further damage? Does earlier intervention result in a
      better functioning testis? Do different surgical techniques differ in their
      success in retaining the testis in the scrotum when dealing with the palpable
      undescended testis? This article reviews the current information on the timing
      and types of surgical intervention of the palpable undescended testes and their
      outcomes. 

PMID- 24871527
TI  - Constant heat stress reduces skeletal muscle protein deposition in broilers.
AB  - BACKGROUND: This experiment was conducted to evaluate the effects of constant
      heat stress on growth performance and protein metabolism in skeletal muscle of
      Arbor Acres broilers. RESULTS: Two hundred and seventy 21-day-old Arbor Acres
      broilers with similar body weight (1298 +/- 28 g) were selected for a 3-week
      trial (29-49 days of age). The broilers were randomly assigned to three groups
      including the control group, constant heat stress group and pair-fed group. Up
      regulation of the rectal temperature and the mRNA expression of heat shock
      protein 70 in liver indicate that the model for constant heat stress was success.
      The average daily gain, feed conversion ratio, breast and thigh muscle weight,
      percentage of breast muscle, crude protein content in breast and thigh muscle in
      constant heat stress group were significantly lower than in control group and
      pair-fed group. Serum uric acid content and the glutamic-oxaloacetic transaminase
      activity were significantly higher, while protein content and glutamic-pyruvate
      transaminase activity were significantly lower in liver of heat stress group than
      of the control and pair-fed groups. The expression of insulin-like growth factor
      1, phosphatidylinositol 3-kinase and p70S6 kinase associated with protein
      synthesis were lower in breast muscle but higher in thigh muscle in heat stress
      group compared to the control or fed-pair groups. In thigh muscles, the
      expression of muscle ring-finger protein-1 and MAFbx associated with protein
      degradation were higher in the heat stress group than in the control and pair-fed
      groups. CONCLUSION: Poor performance of the birds under heat stress may be due to
      lower synthesis and increased degradation of proteins.

PMID- 24871529
TI  - Development of a redox-free Mitsunobu reaction exploiting phosphine oxides as
      precursors to dioxyphosphoranes.
AB  - The development of the first redox-free protocol for the Mitsunobu reaction is
      described. This has been achieved by exploiting triphenylphosphine oxide--the
      unwanted by-product in the conventional Mitsunobu reaction--as the precursor to
      the active P(V) coupling reagent. Multinuclear NMR studies are consistent with
      hydroxyl activation via an alkoxyphosphonium salt.

PMID- 24871530
TI  - Grieving for Auntie Phyllis.

PMID- 24871531
TI  - Retrieval of trapped and broken guide wire with immediate rescue off-pump
      coronary bypass surgery.
AB  - The entrapment, fracture and dislodgement of diagnostic or therapeutic devices
      within the coronary circulation during a procedure are a rare complication
      occurring in 0.2-0.8% of cases. Despite technological improvements, this
      complication is still occurring because coronary angioplasty is often undertaken
      for complex anatomical situations. The complication of device fracture during the
      intervention procedure occurs due to entrapment, overcoiling and excessive
      traction of the guide wire. There has been no agreement as to whether and by
      which technique the immediate removal of the broken fragment of guide wire should
      be done. Here, we report a case of anterolateral myocardial infarction who
      underwent primary percutaneous coronary intervention. During the procedure, the
      guide wire was entrapped within the left anterior descending coronary artery.
      Despite many attempts, the wire could not be removed and even became fractured at
      the femoral insertion site; thus, urgent surgical removal of the wire with vessel
      grafting was done with a successful outcome. This gives a clear message about the
      importance of the ready availability of surgical backup and, particularly, the
      necessity for complex percutaneous interventions. 

PMID- 24871532
TI  - Effects of human adipose-derived stem cells on the regeneration of damaged
      visceral pleural mesothelial cells: a morphological study in a rabbit model.
AB  - OBJECTIVES: Although an alveolar air leak (AAL) after pulmonary resection is a
      troublesome complication that diminishes a patient's quality of life and
      increases medical costs, current treatment and preventive methods for AAL are not
      effective. Therefore, we transplanted adipose-derived stem cells (ASCs) to the
      damaged visceral pleura to facilitate the regeneration of mesothelial cells and
      investigated the possibility of cell therapy as a treatment option for AAL.
      METHODS: Stem cells were isolated and cultured from discarded fat tissues that
      were collected after liposuction procedures. Flow cytometry analysis was
      performed to evaluate their suitability as mesenchymal stem cells. Cultured stem
      cells were seeded onto polyglycolic acid (PGA) sheets and incubated for 5 days.
      Under general anaesthesia, 10 New Zealand rabbits underwent thoracotomies. After
      the visceral pleura was damaged, PGA sheets containing ASCs were transplanted
      into 5 rabbits (ASC group) and PGA sheets without cells were transplanted into
      the other 5 rabbits (control group). Rethoracotomies were performed after 4
      weeks, and the transplanted areas in the visceral pleura were excised for
      analysis. Haematoxylin and eosin and Azan staining were performed. In addition,
      electron microscopic examinations were performed to investigate the
      ultrastructure of the regenerating mesothelium. RESULTS: Cultured stem cells were
      positive for the surface proteins CD13, CD29, CD49d, CD90 and CD105, whereas they
      were negative for CD34, CD45 and human leukocyte antigen (HLA)-DR. The adhesions
      between the transplanted visceral pleura and parietal pleura were weaker in the
      ASC group than in the control group. On histological examination, the mesothelial
      cell monolayer of the visceral pleura was well preserved in the ASC group,
      whereas it was frequently lost in the control group. Electron microscopy
      demonstrated that the mesothelial cell monolayer and its abundant microvilli were
      well preserved in the ASC group, but were absent or disintegrated in the control
      group. CONCLUSIONS: Transplantation of ASCs to the damaged visceral pleura can
      contribute to the treatment and prevention of AAL by improving the regeneration
      of mesothelial cells.

PMID- 24871533
TI  - Who might benefit from early aspirin after coronary artery surgery?
AB  - A best evidence topic in cardiac surgery was written according to a structured
      protocol. The question addressed was whether early administration of aspirin
      might optimize vein graft patency. More than 250 papers were found using the
      reported search, of which 4 new papers in addition to the previous 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. Early postoperative aspirin administered
      within 6 h following coronary artery bypass grafting (CABG) has been shown to be
      optimal for prevention of vein graft occlusion. Early aspirin has significant
      benefit in reducing vein graft occlusion, mortality, myocardial infarction,
      stroke, renal failure and bowel infarction. The efficacy of early postoperative
      aspirin on vein graft patency diminishes the later it is administered. It has
      optimal benefit at 6 h, some benefit at 24 h and no benefit after 48 h post CABG.
      ACC/AHA, EACTS and ACCP have issued guidelines recommending administration of
      early aspirin or an alternative (clopidogrel, ticlopidine and indobufen) at 6 h
      or soon after bleeding has settled as the standard of care for optimization of
      vein graft patency. The ACCP guideline has also suggested that optimal prevention
      of cardiovascular complication should have higher value than prevention of
      postoperative bleeding. Several randomized, controlled studies, including a meta
      analysis, have shown that early administration of aspirin following CABG is not
      associated with increased blood loss or transfusion requirement. Postoperative
      bleeding has been identified as a significant reason for non administration of
      early aspirin in a prospective study. It is essential to define/quantify the
      postoperative blood loss that precludes administration of early aspirin. This
      will enhance prompt administration in some cases and guide judgement, especially
      in patients with high-risk factors for vein graft thrombosis. Administration at 6
      h is the optimal time to give aspirin as long as bleeding has settled. 

PMID- 24871534
TI  - Transcriptome assembly and analysis of Tibetan Hulless Barley (Hordeum vulgare L.
      var. nudum) developing grains, with emphasis on quality properties.
AB  - BACKGROUND: Hulless barley is attracting increasing attention due to its unique
      nutritional value and potential health benefits. However, the molecular biology
      of the barley grain development and nutrient storage are not well understood.
      Furthermore, the genetic potential of hulless barley has not been fully tapped
      for breeding. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we
      investigated the transcriptome features during hulless barley grain development.
      Using Illumina paired-end RNA-Sequencing, we generated two data sets of the
      developing grain transcriptomes from two hulless barley landraces. A total of
      13.1 and 12.9 million paired-end reads with lengths of 90 bp were generated from
      the two varieties and were assembled to 48,863 and 45,788 unigenes, respectively.
      A combined dataset of 46,485 All-Unigenes were generated from two transcriptomes
      with an average length of 542 bp, and 36,278 among were annotated with gene
      descriptions, conserved protein domains or gene ontology terms. Furthermore,
      sequences and expression levels of genes related to the biosynthesis of storage
      reserve compounds (starch, protein, and beta-glucan) were analyzed, and their
      temporal and spatial patterns were deduced from the transcriptome data of
      cultivated barley Morex. CONCLUSIONS/SIGNIFICANCE: We established a sequences and
      functional annotation integrated database and examined the expression profiles of
      the developing grains of Tibetan hulless barley. The characterization of genes
      encoding storage proteins and enzymes of starch synthesis and (1-3;1-4)-beta-D
      glucan synthesis provided an overview of changes in gene expression associated
      with grain nutrition and health properties. Furthermore, the characterization of
      these genes provides a gene reservoir, which helps in quality improvement of
      hulless barley.

PMID- 24871535
TI  - Identifying priority medicines policy issues for New Zealand: a general inductive
      study.
AB  - OBJECTIVES: To identify priority medicines policy issues for New Zealand.
      SETTING: Stakeholders from a broad range of healthcare and policy institutions
      including primary, secondary and tertiary care. PARTICIPANTS: Exploratory,
      semistructured interviews were conducted with 20 stakeholders throughout New
      Zealand. PRIMARY AND SECONDARY OUTCOME MEASURES: The interviews were digitally
      recorded, transcribed and coded into INVIVO 10, then compared and grouped for
      similarity of theme. Perceptions, experiences and opinions regarding New
      Zealand's medicines policy issues were recorded. RESULTS: A large proportion of
      stakeholders appeared to be unaware of New Zealand's (NZ) medicines policy. In
      general, the policy was considered to offer consistency to guide decision-making.
      In the context of Pharmaceutical Management Agency's (PHARMAC's) fixed budget for
      procuring and subsidising medicines, there was reasonable satisfaction with the
      range of medicines available-rare disorder medicines being the clear exception.
      Concerns raised were by whom and how decisions are made and whether desired
      health outcomes are being measured. Other concerns included inconsistencies in
      evidence and across health technologies. Despite attempts to improve the
      situation, lower socioeconomic groups (including rural residents) Maori and
      Pacific ethnicities and people with rare disorders face challenges with regards
      to accessing medicines. Other barriers include, convenience to and affordability
      of prescribers and the increase of prescription fees from NZ$3 to NZ$5. Concerns
      related to the PHARMAC of New Zealand included: a constraining budget; non
      transparency of in-house analysis; lack of consistency in recommendations between
      the Pharmacology and Therapeutics Advisory Committee. Constraints and
      inefficiencies also exist in the submission process to access high-cost
      medicines. CONCLUSIONS: The results suggest reasonable satisfaction with the
      availability of subsidised medicines. However, some of the major challenges
      include access to medicines in vulnerable groups, increasing costs and demand for
      new medicines, access to prescribers, budgetary constraints, cultural and health
      literacy, patient affordability and evidence requirement for gaining subsidy for
      medicines.

PMID- 24871536
TI  - Health inequalities in European cities: perceptions and beliefs among local
      policymakers.
AB  - OBJECTIVE: To describe the knowledge and beliefs of public policymakers on social
      inequalities in health and policies to reduce them in cities from different parts
      of Europe during 2010 and 2011. DESIGN: Phenomenological qualitative study.
      SETTING: 13 European cities. PARTICIPANTS: 19 elected politicians and officers
      with a directive status from 13 European cities. MAIN OUTCOME: Policymaker's
      knowledge and beliefs. RESULTS: Three emerging discourses were identified among
      the interviewees, depending on the city of the interviewee. Health inequalities
      were perceived by most policymakers as differences in life-expectancy between
      population with economic, social and geographical differences. Reducing health
      inequalities was a priority for the majority of cities which use surveys as
      sources of information to analyse these. Bureaucracy, funding and population
      beliefs were the main barriers. CONCLUSIONS: The majority of the interviewed
      policymakers gave an account of interventions focusing on the immediate
      determinants and aimed at modifying lifestyles and behaviours in the more
      disadvantaged classes. More funding should be put towards academic research on
      effective universal policies, evaluation of their impact and training
      policymakers and officers on health inequalities in city governments.

PMID- 24871537
TI  - Care seeking in tuberculosis: results from a countrywide cluster randomised
      survey in Bangladesh.
AB  - OBJECTIVES: To explore systematically the care seeking trajectories of
      tuberculosis (TB) cases up to four subsequent places of care and to assess the
      type of services provided at each place. METHODS: TB cases detected actively
      during the 2007-2009 national TB prevalence survey and passively under the
      routine programme in the same period were interviewed by administering a
      standardised questionnaire. Care seeking and services provided up to four
      subsequent points were explored. Care seeking was further explored by
      categorising the providers into formal, informal and 'self-care' groups. RESULTS:
      A total of 273 TB cases were included in this study, of which 33 (12%) were
      detected during the survey and 240 (88%) from the TB registers. Out of the 118
      passively detected cases who first sought care from an informal provider, 52
      (44.1%) remained in the informal sector at the second point of care. Similarly,
      out of the 52, 17 (32.7%) and out of the 17, 5 (29.4%) remained in the informal
      sector at the third and fourth subsequent points of care, respectively. All the
      33 actively detected cases had 'self-care' at the first point, and 27 (81.8%)
      remained with 'self-care' up to the fourth point of care. Prescribing drugs (59
      99%) was the major type of care provided by the formal and informal care
      providers at each point and was limited to the non-existent practice of
      investigation or referrals. CONCLUSIONS: Free TB services are still underutilised
      by TB cases and informal caregivers remained the major care providers for such
      cases in Bangladesh. In order to improve case detection, it is necessary that the
      National Tuberculosis Programme immediately takes effective initiatives to engage
      all types of care providers, particularly informal providers who are the first
      point of care for the majority of the TB suspects.

PMID- 24871538
TI  - Characterisations of adverse events detected in a university hospital: a 4-year
      study using the Global Trigger Tool method.
AB  - OBJECTIVES: To describe the level, preventability and categories of adverse
      events (AEs) identified by medical record review using the Global Trigger Tool
      (GTT). To estimate when the AE occurred in the course of the hospital stay and to
      compare voluntary AE reporting with medical record reviewing. DESIGN: Two-stage
      retrospective record review. SETTING: 650-bed university hospital. PARTICIPANTS:
      20 randomly selected medical records were reviewed every month from 2009 to 2012.
      PRIMARY AND SECONDARY OUTCOME MEASURES: AE/1000 patient-days. Proportion of AEs
      found by GTT found also in the voluntary reporting system. AE categorisation.
      Description of when during hospital stay AEs occur. RESULTS: A total of 271 AEs
      were detected in the 960 medical records reviewed, corresponding to 33.2 AEs/1000
      patient-days or 20.5% of the patients. Of the AEs, 6.3% were reported in the
      voluntary AE reporting system. Hospital-acquired infections were the most common
      AE category. The AEs occurred and were detected during the hospital stay in 65.5%
      of cases; the rest occurred or were detected within 30 days before or after the
      hospital stay. The AE usually occurred early during the hospital stay, and the
      hospital stay was 5 days longer on average for patients with an AE. CONCLUSIONS:
      Record reviewing identified AEs to a much larger extent than voluntary AE
      reporting. Healthcare organisations should consider using a portfolio of tools to
      gain a comprehensive picture of AEs. Substantial costs could be saved if AEs were
      prevented.

PMID- 24871539
TI  - Is there an association between disease ignorance and self-rated health? The HUNT
      Study, a cross-sectional survey.
AB  - OBJECTIVE: To explore whether awareness versus unawareness of thyroid
      dysfunction, diabetes mellitus or hypertension is associated with self-rated
      health. DESIGN: Large-scale, cross-sectional population-based study. The
      association between thyroid function, diabetes mellitus and blood pressure and
      self-rated health was explored by multiple logistic regression analysis. SETTING:
      The second survey of the Nord-Trondelag Health Study, HUNT2, 1995-1997.
      PARTICIPANTS: 33 734 persons aged 40-70 years. PRIMARY OUTCOME MEASURES: Logistic
      regression was used to estimate ORs for good self-rated health as a function of
      thyroid status, diabetes mellitus status and blood pressure status. RESULTS:
      Persons aware of their hypothyroidism, diabetes mellitus or hypertension reported
      poorer self-rated health than individuals without such conditions. Women with
      unknown and subclinical hypothyroidism reported better self-rated health than
      women with normal thyroid status. In women and men, unknown and probable diabetes
      as well as unknown mild/moderate hypertension was not associated with poorer
      health. Furthermore, persons with unknown severe hypertension reported better
      health than normotensive persons. CONCLUSIONS: People with undiagnosed but
      prevalent hypothyroidism, diabetes mellitus and hypertension often have good self
      rated health, while when aware of their diagnoses, they report reduced self-rated
      health. Use of screening, more sensitive tests and widened diagnostic criteria
      might have a negative effect on perceived health in the population.

PMID- 24871540
TI  - Material, psychosocial and sociodemographic determinants are associated with
      positive mental health in Europe: a cross-sectional study.
AB  - OBJECTIVES: To investigate the association between psychosocial, sociodemographic
      and material determinants of positive mental health in Europe. DESIGN: Cross
      sectional analysis of survey data. SETTING: 34 European countries. PARTICIPANTS:
      Representative Europe-wide sample consisting of 21 066 men and 22 569 women aged
      18 years and over, from 34 European countries participating in the third wave of
      the European Quality of Life Survey (2011-2012). OUTCOME: Positive mental health
      as measured by the WHO-5-Mental Well-being Index, while the lowest 25% centile
      indicated poor positive mental health. RESULTS: The prevalence of poor positive
      mental health was 30% in women and 24% in men. Material, as well as psychosocial,
      and sociodemographic factors were independently associated with poor positive
      mental health in a Europe-wide sample from 34 European countries. When studying
      all factors together, the highest OR for poor positive mental health was reported
      for social exclusion (men: OR=1.73, 95% CI 1.59 to 1.90; women: OR=1.69, 95% CI
      1.57 to 1.81) among the psychosocial factors. Among the material factors,
      material deprivation had the highest impact (men: OR=1.96, 95% CI 1.78 to 2.15;
      women: OR=1.93, 95% CI 1.79 to 2.08). CONCLUSIONS: This study gives the first
      overview on determinants of positive mental health at a European level and could
      be used as the basis for preventive policies in the field of positive mental
      health in Europe.

PMID- 24871542
TI  - Helium bubble nucleation and growth in alpha-Fe: insights from first-principles
      simulations.
AB  - We have carried out a first-principles study on the nucleation and early-stage
      growth of He bubbles in Fe. The energetics, atomic and electronic structure of He
      vacancy complexes, involving both a monovacancy and a nine-vacancy cluster, are
      examined. Based on the energetics, we then perform thermodynamics analysis to
      gain deeper insights into He bubble nucleation and growth. We have determined the
      energy cost for the nucleation of He bubbles and found that up to eight He atoms
      can be trapped at a single vacancy. In order to capture more He atoms, the
      vacancy has to emit Frenkel pairs to release the substantial stress building on
      the surrounding Fe lattice. Compared to the monovacancy, the nine-vacancy cluster
      has a lower energy cost for He bubble nucleation and growth. He atoms at the
      vacancy repel the surrounding electronic charge and redistribute it on the
      neighboring Fe atoms. The thermodynamic analysis reveals that He chemical
      potential provides a driving force for He bubble nucleation and growth. There are
      two critical He chemical potentials that are of particular importance: one of
      them marks the transition from single He occupation to multiple He occupation at
      a monovacancy while the other sets off He-induced superabundant vacancy
      formation. 

PMID- 24871541
TI  - STOP-Bang and the effect on patient outcome and length of hospital stay when
      patients are not using continuous positive airway pressure.
AB  - BACKGROUND: In patients undergoing surgical interventions under general
      anesthesia, obstructive sleep apnea syndrome (OSA) can cause serious
      perioperative cardiovascular or respiratory complications leading to fatal
      consequences, even sudden death. In this study we test the hypothesis that
      morbidly obese patients diagnosed by a polysomnography test and using continuous
      positive airway pressure (CPAP) therapy have fewer and less severe perioperative
      complications and a shorter hospital stay than patients who have a medical
      history that meets at least three STOP-Bang criteria and are not using CPAP
      therapy. METHODS: Postoperative hospital stay and pulmonary complications were
      analyzed in three groups of morbidly obese patients undergoing bariatric surgery
      (Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy) between January
      2009 and November 2013 (n = 693). Group A comprised 99 patients who were
      preoperatively diagnosed with OSA based on polysomnography results. These
      patients used CPAP therapy before and after surgery. Group B consisted of 182
      patients who met at least three STOP-Bang criteria but who were not diagnosed
      with OSA based on polysomnography results. These patients did not use CPAP. Group
      C, the reference group, comprised 412 patients who scored one to two items on the
      STOP-Bang. RESULTS: During the perioperative period, Group B patients had a
      significantly (p < 0.001) higher cumulative rate of pulmonary complications,
      worse oxygen saturation, respiratory rates, and increased length of stay in
      hospital. There was also two cases of sudden death in this group. CONCLUSION:
      Based on these results, we conclude that patients meeting at least three STOP
      BANG criteria have higher postoperative complications and an increased length of
      hospital stay than patients using CPAP.

PMID- 24871543
TI  - Glucose tolerance test before and after gastroplasty. Is it a secure measurement?

PMID- 24871544
TI  - Bacterial antigens and molecular mimicry: the bridging common problematic link in
      the pathogenesis of sarcoidosis and sarcoid-like reactions: Isn't it time to wake
      up?

PMID- 24871545
TI  - In vivo amphetamine action is contingent on alphaCaMKII.
AB  - Addiction to psychostimulants (ie, amphetamines and cocaine) imposes a major
      socioeconomic burden. Prevention and treatment represent unmet medical needs,
      which may be addressed, if the mechanisms underlying psychostimulant action are
      understood. Cocaine acts as a blocker at the transporters for dopamine (DAT),
      serotonin (SERT), and norepinephrine (NET), but amphetamines are substrates that
      do not only block the uptake of monoamines but also induce substrate efflux by
      promoting reverse transport. Reverse transport has been a focus of research for
      decades but its mechanistic basis still remains enigmatic. Recently, transporter
      interacting proteins were found to regulate amphetamine-triggered reverse
      transport: calmodulin kinase IIalpha (alphaCaMKII) is a prominent example,
      because it binds the carboxyl terminus of DAT, phosphorylates its amino terminus,
      and supports amphetamine-induced substrate efflux in vitro. Here, we investigated
      whether, in vivo, the action of amphetamine was contingent on the presence of
      alphaCaMKII by recording the behavioral and neurochemical effects of amphetamine.
      Measurement of dopamine efflux in the dorsal striatum by microdialysis revealed
      that amphetamine induced less dopamine efflux in mice lacking alphaCaMKII.
      Consistent with this observation, the acute locomotor responses to amphetamine
      were also significantly blunted in alphaCaMKII-deficient mice. In addition, while
      the rewarding properties of amphetamine were preserved in alphaCaMKII-deficient
      mice, their behavioral sensitization to amphetamine was markedly reduced. Our
      findings demonstrate that amphetamine requires the presence of alphaCaMKII to
      elicit a full-fledged effect on DAT in vivo: alphaCaMKII does not only support
      acute amphetamine-induced dopamine efflux but is also important in shaping the
      chronic response to amphetamine. 

PMID- 24871546
TI  - The role of GluN2A and GluN2B subunits on the effects of NMDA receptor
      antagonists in modeling schizophrenia and treating refractory depression.
AB  - Paradoxically, N-methyl-D-aspartate (NMDA) receptor antagonists are used to model
      certain aspects of schizophrenia as well as to treat refractory depression.
      However, the role of different subunits of the NMDA receptor in both conditions
      is poorly understood. Here we used biochemical and behavioral readouts to examine
      the in vivo prefrontal efflux of serotonin and glutamate as well as the
      stereotypical behavior and the antidepressant-like activity in the forced swim
      test elicited by antagonists selective for the GluN2A (NVP-AAM077) and GluN2B (Ro
      25-6981) subunits. The effects of the non-subunit selective antagonist, MK-801;
      were also studied for comparison. The administration of MK-801 dose dependently
      increased the prefrontal efflux of serotonin and glutamate and markedly increased
      the stereotypy scores. NVP-AAM077 also increased the efflux of serotonin and
      glutamate, but without the induction of stereotypies. In contrast, Ro 25-6981 did
      not change any of the biochemical and behavioral parameters tested.
      Interestingly, the administration of NVP-AAM077 and Ro 25-6981 alone elicited
      antidepressant-like activity in the forced swim test, in contrast to the
      combination of both compounds that evoked marked stereotypies. Our interpretation
      of the results is that both GluN2A and GluN2B subunits are needed to induce
      stereotypies, which might be suggestive of potential psychotomimetic effects in
      humans, but the antagonism of only one of these subunits is sufficient to evoke
      an antidepressant response. We also propose that GluN2A receptor antagonists
      could have potential antidepressant activity in the absence of potential
      psychotomimetic effects. 

PMID- 24871548
TI  - Group B betacoronavirus in rhinolophid bats, Japan.
AB  - We report group B Betacoronavirus infection in little Japanese horseshoe bats in
      Iwate prefecture. We then used reverse-transcription PCR to look for the
      coronavirus RNA-dependent RNA polymerase gene in fecal samples collected from 27
      little Japanese horseshoe bats and found eight were provisionally positive. We
      had a success in the nucleotide sequencing of six of the eight positive samples
      and compared them with those of authentic coronaviruses. We found that these six
      samples were positive in coronavirus infection, and they belonged to the group B
      Betacornavirus by phylogenetic analysis. Virus isolation using the Vero cell
      culture was unsuccessful. Pathogenic trait of these bat coronaviruses remained
      unexplored. 

PMID- 24871547
TI  - Memantine effects on verbal memory in fragile X-associated tremor/ataxia syndrome
      (FXTAS): a double-blind brain potential study.
AB  - Older FMR1 premutation carriers may develop fragile X-associated tremor/ataxia
      syndrome (FXTAS), a neurodegenerative disorder manifesting cognitive deficits
      that often subsequently progress to dementia. To date, there is no specific
      treatment available for FXTAS. Studies have demonstrated the premutation
      associated overactivation of glutamatergic receptors in neurons. Memantine, a
      NMDA receptor antagonist approved for treatment of Alzheimer's disease, thus was
      tested in the first placebo-controlled, double-blind, randomized clinical trial
      in FXTAS. Prior event-related brain potential (ERP) studies in FXTAS found
      reduced N400 repetition effect, a glutamate-related electrophysiological marker
      of semantic priming, and verbal memory processes. This substudy of the randomized
      clinical trial of memantine in FXTAS sought to use the N400 repetition effect to
      evaluate effects of chronic memantine treatment on verbal memory. Subsequent
      recall and recognition memory tests for the experimental stimuli were
      administered to characterize verbal memory. Data from 41 patients who completed
      the 1-year memantine trial (21 on memantine) and also completed longitudinal ERP
      studies were analyzed. Results showed treatment-associated benefits on both cued
      recall memory and N400 repetition effect amplitude. Importantly, improvement in
      cued recall was positively correlated with amplitude increase of the N400
      repetition effect. The placebo group, in contrast, displayed a significant
      reduction of the N400 repetition effect after 1 year. These results suggest that
      memantine treatment may have beneficial effects on verbal memory in FXTAS.
      Additional studies of memantine, perhaps in combination with other therapeutic
      agents, appear warranted, as symptomatic treatments and neuroprotective
      treatments are both needed for this recently recognized neurodegenerative
      disorder. 

PMID- 24871549
TI  - Unpredictable chronic stress-induced reproductive suppression associated with the
      decrease of kisspeptin immunoreactivity in male mice.
AB  - Environmental stress affects various parts of mammals typically through the
      circulation of stress hormones. It has been identified as one of the possible
      reasons for male reproductive difficulties, but the complex mechanisms
      responsible for stress-induced reproductive suppression are poorly understood.
      Here, we examined the relationship between chronic environmental stress and
      hypothalamic kisspeptin, a recently discovered upstream regulator of the
      reproductive endocrine feedback system. We studied male mice under an
      unpredictable chronic stress procedure to replicate the situation of animals
      under chronic stress. Histological and immunohistochemical analyses were
      performed focusing on kisspeptin neurons in the arcuate hypothalamic nucleus
      (ARC) and DNA fragmented cells in seminiferous tubules. Although the ARC was not
      morphologically altered in either the stressed or non-stressed group, granular
      kisspeptin immunoreactivities decreased slightly in the stress group. In the
      testes of the stress group, several signs of testicular degeneration were
      observed, including increased numbers of ssDNA-positive cells per seminiferous
      tubule, thinning, vacuoled seminiferous epithelia and multinucleated giant cells.
      The decreases in kisspeptin in the stress group might be due to other
      hypothalamic peptides, such as corticotropin-releasing hormone and leptin, whose
      receptors are known to coexpress in the ARC. In addition, environmental stress
      directly and indirectly affects testicular function through stress hormones and
      gonadotropins. In summary, our findings enhance the understanding of stress
      induced reproductive suppression possibly mediated by kisspeptin in the ARC. 

PMID- 24871550
TI  - The effect of polysorbate 20 on solubility and stability of candesartan cilexetil
      in dissolution media.
AB  - The addition of polysorbate 20 (T20) is required to achieve "sink" conditions
      during a dissolution test for tablets with candesartan cilexetil (CC).
      Polysorbate 20 (0.35%-0.7% w/w) added to 0.05 mol/L of phosphate buffer pH 6.5
      dramatically increased the apparent solubility of the drug from 0.8 MUg/ml even
      to 353 MUg/ml, while its effect in lower pH or in water was much smaller (20
      MUg/ml in pH 4.5). The increased concentration of phosphate salts (0.2 mol/l) at
      pH 6.5 in the presence of 0.7% of polysorbate 20, resulted in further increase of
      candesartan cilexetil solubility to 620 MUg/ml. The change of pH from 1.2 to 7.4
      resulted in a 1.5-fold increase of the activation energy and, depending on
      temperature, 8-14-fold decrease of the degradation rate. When polysorbate 20
      increased the activation energy 2-fold, independent of pH, it protected
      candesartan cilexetil from degradation; however, this effect was temperature
      dependent and was very small at 310 K-the degradation rate in pH 6.5 decreased by
      13% only. It was calculated that in the phosphate buffer pH 6.5 with polysorbate,
      one can expect during 24 h the degradation at the level of 9.3%, thus a flow
      through dissolution apparatus was recommended for testing prolonged release
      dosage forms. 

PMID- 24871551
TI  - Investigation of dry powder inhaler (DPI) resistance and aerosol dispersion
      timing on emitted aerosol aerodynamic particle sizing by multistage cascade
      impactor when sampled volume is reduced from compendial value of 4 L.
AB  - Compendial methods determining dry powder inhaler (DPI)-emitted aerosol
      aerodynamic particle size distribution (APSD) collect a 4-L air sample containing
      the aerosol bolus, where the flow, which propagates through the cascade impactor
      (CI) measurement system from the vacuum source, is used to actuate the inhaler. A
      previous article described outcomes with two CIs (Andersen eight-stage cascade
      impactor (ACI) and Next-Generation Pharmaceutical Impactor (NGI)) when the air
      sample volume was <=4 L with moderate-resistance DPIs. This article extends that
      work, examining the hypothesis that DPI flow resistance may be a factor in
      determining outcomes. APSD measurements were made using the same CI systems with
      inhalers representing low and high flow resistance extremes (Cyclohaler(r) and
      HandiHaler(r) DPIs, respectively). The ratio of sample volume to internal dead
      space (normalized volume (V*)) was varied from 0.25 to 1.98 (NGI) and from 0.43
      to 3.46 (ACI). Inhaler resistance was a contributing factor to the rate of bolus
      transfer; the higher resistance DPI completing bolus relocation to the NGI pre
      separator via the inlet when V* was as small as 0.25, whereas only ca. 50% of the
      bolus mass was collected at this condition with the Cyclohaler(r) DPI. Size
      fractionation of the bolus from either DPI was completed within the ACI at
      smaller values of V* than within the NGI. Bolus transfer from the Cyclohaler(r)
      capsule and from the HandiHaler(r) to the ACI system were unaffected by the
      different flow rise time observed in the two different flow controller systems,
      and the effects the ACI-based on APSD measurements were marginal. 

PMID- 24871556
TI  - Changing hafnium speciation in aqueous sulfate solutions: a high-energy X-ray
      scattering study.
AB  - The relationship of solution speciation and the structures of corresponding
      precipitates is examined for an aqueous Hf(4+) sulfate series. High-energy X-ray
      scattering (HEXS) and Raman spectroscopy data are used to probe atomic
      correlations in solutions. Hf(4+) in acidic perchlorate solution shows no
      evidence of a mononuclear metal species but instead has a peak in the pair
      distribution function (PDF), generated from the HEXS data, at 3.55 A, indicating
      Hf(4+)-Hf(4+) solution correlations. The peak intensity is consistent with
      clusters that are, on average, larger than the tetramic unit [M4(OH)8(H2O)16](8+)
      usually attributed to Zr(4+) and Hf(4+) solution speciation under these
      conditions. Addition of sulfate results in a breakup of hydroxo-bridged oligomers
      into sulfate-capped dimers and, for higher concentrations, Hf-sulfate monomers.
      The bidentate coordination mode of sulfate dominates the dissolved precursors,
      although it is not found in the structure of the final crystallized product,
      which instead is comprised of bridging-bidentate sulfate ligation. Neither the
      PDF patterns nor the Raman spectra show any evidence of the larger oligomers,
      such as the octadecameric metal clusters, found in similar Zr(4+) solutions. The
      oligomeric units found in solution provide insights into possible assembly routes
      for crystallization. In addition to expanding our understanding of synthesis
      science this study also reveals differences in the aqueous chemistries between Hf
      and Zr, two elements with ostensibly very similar chemical behavior. 

PMID- 24871552
TI  - The practicality of mesoporous silica nanoparticles as drug delivery devices and
      progress toward this goal.
AB  - Mesoporous silica nanoparticles (MSNs) have been proposed as drug delivery
      devices for approximately 15 years. The history of in vitro studies has been
      promising, demonstrating that MSNs have the capability for stimulus-responsive
      controlled release, good cellular uptake, cell specific targeting, and the
      ability to carry a variety of cargoes from hydrophobic drug molecules to imaging
      agents. However, the translation of the in vitro findings to in vivo conditions
      has been slow. Herein, we review the current state-of-the-art in the use of MSN
      for systemic drug delivery in vivo and provide critical insight into the future
      of MSNs as systemic drug delivery devices and directions that should be
      undertaken to improve their practicality. 

PMID- 24871553
TI  - A new lipid-based nano formulation of vinorelbine.
AB  - Vinorelbine (VLB) is a semi-synthetic Vinca alkaloid which is currently used in
      treatment of different cancer types mainly advanced breast cancer (ABC) and
      advanced/metastatic non-small cell lung cancer (NSCLC). However, its marketed
      formulation has been reported to have serious side effects, such as
      granulocytopenia, which is the major dose-limiting toxicity. Other unwanted
      effects include venous discoloration and phlebitis proximal to the site of
      injection, as well as localized rashes and urticaria, blistering, and skin
      sloughing. Our long-term aim in synthesizing a novel nanomicellar vinorelbine
      formulation is to reduce or even eliminate these side effects and increase drug
      activity by formulating the drug in a lipid-based system as a nanomedicine
      targeted to the site of action. To this end, the purpose of this study was to
      prepare, characterize, and determine the in vitro efficacy of vinorelbine-loaded
      sterically stabilized, biocompatible, and biodegradable phospholipid nanomicelles
      (SSM; size, ~15 nm). Our results indicated that vinorelbine incorporate at high
      quantities and within the interface between the core and palisade sections of the
      micelles. Incorporation ratio of drug within sterically stabilized micelles
      increased as the total amount of drug in the system increased, and no drug
      particles were formed at the highest drug concentrations tested. The nanomicellar
      formulation of vinorelbine was ~6.7-fold more potent than vinorelbine dissolved
      in DMSO on MCF-7 cell line. Collectively, these data indicate that vinorelbine
      loaded SSM can be developed as a new, safe, stable, and effective nanomedicine
      for the treatment of breast and lung cancers. 

PMID- 24871554
TI  - Investigation of the stabilizing effects of antioxidants and benzophenone-3 on
      desonide photostability.
AB  - Desonide is a topical corticoid used in the treatment of skin diseases and is
      marketed in different pharmaceutical dosage forms. Recently, the poor
      photostability of a commercially available hair solution after direct exposure to
      UVA light was verified. In this study, we investigated the ability of the
      antioxidants ascorbic acid, butylhydroxyanisole (BHA), butylhydroxytoluene (BHT),
      alpha-tocopherol, and the UV filter benzophenone-3 (BP-3) to prevent the
      photodegradation of desonide in hair solution (desonide 0.1%) and the stability
      of the proposed formulation under environmental conditions. The tested
      antioxidants were not able to prevent the photolysis of desonide, whereas the
      addition of 0.3% BP-3 enhanced the photostability of the drug. After 15 h of
      direct exposure to UVA radiation, the desonide remaining content in the hair
      solution with BP-3 was approximately 98%. Higher photostability was also verified
      under UVC radiation. Additionally, the results indicated that the formulation was
      stable under accelerated and room temperature conditions for 70 days,
      corresponding to the total period of the study. 

PMID- 24871558
TI  - RAD51 G135C gene polymorphism and risk of colorectal cancer in Kashmir.
AB  - RAD51 - a DNA double-strand breaks repair gene plays an important role in
      homologous recombination, a process frequently involved in cancer transformation.
      The aim of this study was to compare the distribution of the genotype of the
      RAD51 G135C polymorphism between colorectal cancer (CRC) patients and controls.
      We also tested the association between the G135C polymorphism of the RAD51 gene
      and the risk of CRC, and various clinicopathological parameters. Polymorphism was
      evaluated by restriction fragment length polymorphism PCR in 100 CRC patients and
      120 age-matched and sex-matched controls. There was a significant association
      between RAD51 genotypes and CRC cases (P<0.05). Also, the GC genotype was
      associated with an increased risk of CRC (odds ratio >3.84). Our results suggest
      that the G135C polymorphism of the RAD51 gene is associated with an increased
      risk of CRC in our population. 

PMID- 24871557
TI  - Inhibitory effects of Baccharis dracunculifolia on 1,2-dimethylhidrazine-induced
      genotoxicity and preneoplastic lesions in rat colon.
AB  - Baccharis dracunculifolia (Asteraceae), the main botanical source of green
      propolis, also known as 'alecrim-do-campo' and 'vassourinha', is a shrub of the
      Brazilian 'cerrado' and is native to the South and Southeast of Brazil. The
      effects of B. dracunculifolia ethyl acetate extract (Bd-EAE) were evaluated on
      the 1,2-dimethylhydrazine (DMH)-induced DNA damage and aberrant crypt foci (ACF)
      in the colon of male Wistar rats by the comet and ACF assays, respectively. The
      animals were treated by gavage with doses of 6, 12, and 24 mg/kg body weight/day.
      Animals were also administered a single subcutaneous injection of 40 mg/kg DMH
      and were killed after 4 h for evaluation of DNA damage. Also, two doses of 40
      mg/kg of DMH were administered weekly for 2 weeks, and animals were killed 2
      weeks after the last injection for evaluation of ACF development in the colon.
      The results showed a significant reduction in the frequency of DNA damage and ACF
      in the group treated with the Bd-EAE plus DMH in comparison with those treated
      with DMH alone, suggesting that Bd-EAE reduced DNA damage and suppressed the
      formation of ACF and also exerted a protective affect against colon
      carcinogenesis. 

PMID- 24871560
TI  - Breast cancer in low-resource settings: prioritizing the awareness and access
      programmes to overcome sociocultural and economic barriers for early detection
      and improved outcomes.

PMID- 24871559
TI  - Chemopreventive and chemotherapeutic effect of a novel histone deacetylase
      inhibitor, by specificity protein 1 in MDA-MB-231 human breast cancer cells.
AB  - Histone deacetylase inhibitors (HDACi) have been reported to have potent
      chemopreventive activity because of their effects on the inhibition of cell
      growth and apoptosis in human cancer cell lines. In the present study, we
      investigated the apoptotic effect of a novel HDACi, Ky2, and its molecular
      mechanism in MDA-MB-231 human breast cancer cells in vitro. The chemopreventive
      effects of Ky2 in MDA-MB-231 cells were evaluated using the MTS assay, anchorage
      independent cell transformation assay, DAPI staining, western blot analysis,
      reverse transcriptase-PCR, and small interfering RNA. Ky2 enhanced histone
      acetylation and decreased cell viability. Ky2 induced apoptosis evidenced by
      nuclear condensation and fragmentation, the accumulation of sub-G1 phase, and
      caspase-dependent PARP cleavage. In addition, Ky2 released cytochrome c from
      mitochondria to cytosol through the regulation of mitochondria-related proteins
      (Bid, Bim, and Bcl-xL). Ky2 markedly decreased the level of Sp1 protein
      expression through both the decrease of Sp1 mRNA level and proteasome-dependent
      protein degradation. Interestingly, the apoptotic effect of Ky2 is more potent
      than SAHA, a well-known HDACi. Furthermore, the knockdown of Sp1 protein by Sp1
      specific inhibitor, mithramycin A, and siRNA resulted in the alteration of
      truncated Bid and Bim to induce apoptosis. Furthermore, Ky2 significantly
      decreased TPA-induced or EGF-induced neoplastic cell transformation in JB6 cells.
      Our results suggest that Ky2 may be a potential chemopreventive and
      chemotherapeutic agent by modulating Sp1 in human breast cancer cells. 

PMID- 24871561
TI  - Acceptability of human papilloma virus vaccination among primary school girls in
      Minakulu sub-county, northern Uganda.

PMID- 24871562
TI  - Evaluation of a sun safety education programme for primary school students in
      Switzerland.
AB  - The incidence of skin cancer has increased worldwide, with rates being especially
      high in Switzerland compared with other European countries. Extensive sun
      exposure during childhood is considered a key factor for skin carcinogenesis. The
      aim of the study was to evaluate the impact of a school-based sun safety
      education programme developed by the Swiss Cancer Leagues on primary school
      students' sun-related knowledge, protective behaviours and sunburn rates. In
      summer 2011, 1-h sun safety education sessions were held at 33 primary schools
      throughout the Canton of Zurich (North-Eastern Switzerland). Children in the
      participating school classes (first, second and third graders) answered a
      questionnaire on their sun-related knowledge, behaviours and sunburn experience
      shortly before and 1 year after the intervention. Overall, 3110 completed pretest
      and 1738 post-test questionnaires were eligible for analysis. The evaluation of
      pretest data showed considerable room for improvement in terms of sun-related
      knowledge, considering that merely a good half of the children were conscious
      that the sun may present a hazard to health. Overall, more than 95% of students
      benefited from the protection of sunscreen (application by parents: 73%;
      application by child: 66%), but only 36% stated that they generally sought shade
      on sunny days. After the intervention, knowledge increased considerably and
      significantly (P<0.0001), but there was no change in sun-protective behaviours
      (use of sunscreen, seeking shade). However, we observed a nonsignificant trend
      towards decreased sunburn rates. The brief one-time sun safety education sessions
      were effective in sustainably improving children's sun-related knowledge and
      possibly to some extent in decreasing their sunburn rates. 

PMID- 24871563
TI  - Tobacco smoking patterns and differential food effects on prostate and breast
      cancers among smokers and nonsmokers in Cordoba, Argentina.
AB  - The aim of this study was to estimate the effect of diet on prostate and breast
      cancer (PC and BC) risks in smokers and nonsmokers and to explore the effect
      modification between smoking and dietary patterns. PC or BC incidence rates were
      assessed spatially according to tobacco exposure, age-adjusted standardization
      using lung cancer mortality as a proxy. Two case-control studies were carried out
      in Argentina (2008-2012). Participants were interviewed about their diet, smoking
      habits, and other lifestyle factors. Multilevel models were fitted including
      family history of cancer as the random intercept for the second level, and diet
      and lifestyle variables as covariates. Tobacco exposure was aggregated spatially.
      Family history of cancer significantly accounts for PC and BC. In smokers, high
      intake of fat meat increased PC and BC risks [odds ratio (OR) 1.56, 95%
      confidence interval (CI) 0.81-3.05 and OR 6.01, 95% CI 1.99-8.19, respectively].
      PC and BC risks were also greater in smokers with high intakes of fatty foods (OR
      1.95, 95% CI 1.09-3.50 and OR 24.2, 95% CI 0.82-7.21, respectively). Moderate
      intake of nonstarchy vegetables and risk of PC were inversely associated in
      nonsmokers (OR 0.55, 95% CI 0.20-1.48). In smoker women, BC risk was associated
      with sweet drink consumption (OR 2.96, 95% CI 1.10-7.92) and ethanol intake (OR
      5.15, 95% CI 1.88-14.16). Spatial distributions of cancer incidence rates match
      those of tobacco exposure. Differential effects of diet on PC and BC risks were
      found in smokers and nonsmokers. 

PMID- 24871565
TI  - Metal ions and intrinsically disordered proteins and peptides: from Cu/Zn amyloid
      beta to general principles.
AB  - The interaction of d-block metal ions (Cu, Zn, Fe, etc.) with intrinsically
      disordered proteins (IDPs) has gained interest, partly due to their proposed
      roles in several diseases, mainly neurodegenerative. A prominent member of IDPs
      is the peptide amyloid-beta (Abeta) that aggregates into metal-enriched amyloid
      plaques, a hallmark of Alzheimer's disease, in which Cu and Zn are bound to
      Abeta. IDPs are a class of proteins and peptides that lack a unique 3D structure
      when the protein is isolated. This disordered structure impacts their interaction
      with metal ions compared with structured metalloproteins. Metalloproteins either
      have a preorganized metal binding site or fold upon metal binding, resulting in
      defined 3D structure with a well-defined metal site. In contrast, for Abeta and
      likely most of the other IDPs, the affinity for Cu(I/II) and Zn(II) is weaker and
      the interaction is flexible with different coordination sites present.
      Coordination of Cu(I/II) with Abeta is very dynamic including fast Cu-exchange
      reactions (milliseconds or less) that are intrapeptidic between different sites
      as well as interpeptidic. This highly dynamic metal-IDP interaction has a strong
      impact on reactivity and potential biological role: (i) Due to the low affinity
      compared with classical metalloproteins, IDPs likely bind metals only at special
      places or under special conditions. For Abeta, this is likely in the neurons that
      expel Zn or Cu into the synapse and upon metal dysregulation occurring in
      Alzheimer's disease. (ii) Amino acid substitutions (mutations) on noncoordinating
      residues can change drastically the coordination sphere. (iii) Considering the
      Cu/Zn-Abeta aberrant interaction, therapeutic strategies can be based on removal
      of Cu/Zn or precluding their binding to the peptide. The latter is very difficult
      due to the multitude of metal-binding sites, but the fast koff facilitates
      removal. (iv) The high flexibility of the Cu-Abeta complex results in different
      conformations with different redox activity. Only some conformations are able to
      produce reactive oxygen species. (v) Other, more specific catalysis (like
      enzymes) is very unlikely for Cu/Zn-Abeta. (vi) The Cu/Zn exchange reactions with
      Abeta are faster than the aggregation process and can hence have a strong impact
      on this process. In conclusion, the coordination chemistry is fundamentally
      different for most of IDPs compared with the classical, structured
      metalloproteins or with (bio)-inorganic complexes. The dynamics is a key
      parameter to understand this interaction and its potential biological impact.

PMID- 24871564
TI  - Junctional cleft [Ca2+]i measurements using novel cleft-targeted Ca2+ sensors.
AB  - RATIONALE: Intracellular Ca(2+) concentration ([Ca(2+)]i) is regulated and
      signals differently in various subcellular microdomains, which greatly enhances
      its second messenger versatility. In the heart, sarcoplasmic reticulum Ca(2+)
      release and signaling are controlled by local [Ca(2+)]i in the junctional cleft
      ([Ca(2+)]Cleft), the small space between sarcolemma and junctional sarcoplasmic
      reticulum. However, methods to measure [Ca(2+)]Cleft directly are needed.
      OBJECTIVE: To construct novel sensors that allow direct measurement of
      [Ca(2+)]Cleft. METHODS AND RESULTS: We constructed cleft-targeted [Ca(2+)]
      sensors by fusing Ca(2+)-sensor GCaMP2.2 and a new lower Ca(2+)-affinity variant
      GCaMP2.2Low to FKBP12.6, which binds with high affinity and selectivity to
      ryanodine receptors. The fluorescence pattern, affinity for ryanodine receptors,
      and competition by untagged FKBP12.6 demonstrated that FKBP12.6-tagged sensors
      are positioned to measure local [Ca(2+)]Cleft in adult rat myocytes. Using
      GCaMP2.2Low-FKBP12.6, we showed that [Ca(2+)]Cleft reaches higher levels with
      faster kinetics than global [Ca(2+)]i during excitation-contraction coupling.
      Diastolic sarcoplasmic reticulum Ca(2+) leak or sarcolemmal Ca(2+) entry may
      raise local [Ca(2+)]Cleft above bulk cytosolic [Ca(2+)]i ([Ca(2+)]Bulk), an
      effect that may contribute to triggered arrhythmias and even transcriptional
      regulation. We measured this diastolic standing [Ca(2+)]Cleft-[Ca(2+)]Bulk
      gradient with GCaMP2.2-FKBP12.6 versus GCaMP2.2, using [Ca(2+)] measured without
      gradients as a reference point. This diastolic difference ([Ca(2+)]Cleft=194
      nmol/L versus [Ca(2+)]Bulk=100 nmol/L) is dictated mainly by the sarcoplasmic
      reticulum Ca(2+) leak rather than sarcolemmal Ca(2+) flux. CONCLUSIONS: We have
      developed junctional cleft-targeted sensors to measure [Ca(2+)]Cleft versus
      [Ca(2+)]Bulk and demonstrated dynamic differences during electric excitation and
      a standing diastolic [Ca(2+)]i gradient, which could influence local Ca(2+)
      dependent signaling within the junctional cleft.

PMID- 24871566
TI  - Benzyl alcohol increases voluntary ethanol drinking in rats.
AB  - The anabolic steroid nandrolone decanoate has been reported to increase voluntary
      ethanol intake in Wistar rats. In recent experiments we received opposite
      results, with decreased voluntary ethanol intake in both high drinking AA and low
      drinking Wistar rats after nandrolone treatment. The difference between the two
      studies was that we used pure nandrolone decanoate in oil, whereas in the
      previous study the nandrolone product Deca-Durabolin containing benzyl alcohol
      (BA) was used. The aims of the present study were to clarify whether the BA
      treatment could promote ethanol drinking and to assess the role of the
      hypothalamic-pituitary-adrenal-gonadal axes (HPAGA) in the potential BA effect.
      Male AA and Wistar rats received subcutaneously BA or vehicle oil for 14 days.
      Hereafter followed a 1-week washout and consecutively a 3-week voluntary alcohol
      consumption period. The median (+/- median absolute deviation) voluntary ethanol
      consumption during the drinking period was higher in BA-treated than in control
      rats (4.94 +/- 1.31 g/kg/day vs. 4.17 +/- 0.31 g/kg/day, p = 0.07 and 1.01 +/-
      0.26 g/kg/day vs. 0.38 +/- 0.27 g/kg/day, p = 0.05, for AA and Wistar rats,
      respectively; combined effect p < 0.01). The present results can explain the
      previous discrepancy between the two nandrolone studies. No significant BA
      effects on basal and ethanol-mediated serum testosterone and corticosterone
      levels were observed in blood samples taken at days 1, 8 and 22. However, 2h
      after ethanol administration significantly (p = 0.02) higher frequency of
      testosterone elevations was detected in high drinking AA rats compared to low
      drinking Wistars, which supports our previous hypotheses of a role of
      testosterone elevation in promoting ethanol drinking. Skin irritation and
      dermatitis were shown exclusively in the BA-treated animals. Altogether, the
      present results indicate that earlier findings obtained with Deca-Durabolin
      containing BA need to be re-evaluated.

PMID- 24871567
TI  - Protective effect of hesperetin in rat model of partial sciatic nerve ligation
      induced painful neuropathic pain: an evidence of anti-inflammatory and anti
      oxidative activity.
AB  - Behavioral, biochemical and gene expression changes were investigated in a rat
      model of partial sciatic nerve ligation (PSNL) after administration of hesperetin
      (20, 50mg/kg; p.o.), pregabalin (10mg/kg; p.o.) or vehicle (1 ml/kg, p.o.).
      Thirty-six animals were randomly divided into six groups. Left sciatic nerve was
      exposed and ligated, animals in the control and test groups were treated orally
      with respective drugs for fifteen days. Nociceptive threshold was assessed on 0
      day and thereafter every three days. Three weeks later, sciatic nerve tissue
      homogenate was prepared and subjected for estimation of oxidative markers namely
      total protein, nitric oxide, lipid peroxidase, interleukins (IL-1beta and IL-6)
      and TNF-alpha. Administration of hesperetin resulted in a dose dependent
      attenuation in PSNL-induced mechanical and thermal hyperalgesia, mechanical
      allodynia as well as down regulation of IL-1beta, IL-6 and TNF-alpha, and
      biochemical markers. Consequently, it can be concluded that anti-hyperalgesic
      effect of hesperetin in rats after PSNL may be attributed to various oxidative
      markers as well as the pro-inflammatory mediators secreted at the injury site.
      Hesperetin appears to be a promising candidate for the development as a novel
      therapeutic for the patients suffering from the neuropathic pain.

PMID- 24871568
TI  - Vasopressin Associated With an Increase in Return of Spontaneous Circulation in
      Acidotic Cardiopulmonary Arrest Patients.
AB  - BACKGROUND: During respiratory and metabolic acidosis, the vasoconstrictive
      effects of epinephrine may be blunted, whereas the response to vasopressin
      remains unchanged. The impact of this effect during advanced cardiac life support
      (ACLS) remains unclear. OBJECTIVE: Determine if vasopressin therapy in
      combination with epinephrine was associated with improved outcomes in patients
      with cardiac arrest compared to epinephrine alone. The primary outcome was
      difference in rate of return of spontaneous circulation (ROSC). Secondary
      outcomes included evaluation of rates of ROSC for patients with an initial pH
      <7.2 and by initial pulseless rhythm. METHODS: Single-center, retrospective
      review conducted from July 2010 to July 2012. Patients >=18 years of age with
      documented cardiac arrest requiring ACLS and vasopressor therapy were included.
      RESULTS: A total of 101 patients met inclusion criteria. There was no difference
      in rate of ROSC (56% vs 60%, P = 0.68) or survival to hospital discharge (9% vs
      5%, P = 0.46) between patients who received vasopressin in combination with
      epinephrine (n = 43) compared to epinephrine alone (n = 58). Subgroup analysis of
      ROSC in patients with an arterial pH of <7.2 (n = 35) showed an increased rate of
      ROSC (63% vs 37%, P = 0.01) in the vasopressin plus epinephrine group versus the
      epinephrine alone group, respectively. Subgroup analysis by initial cardiac
      rhythm showed no difference in rate of ROSC. CONCLUSIONS: Vasopressin in
      combination with epinephrine demonstrated improved ROSC in cardiac arrest
      patients with initial arterial pH <7.2 compared with epinephrine alone, without
      improving survival to hospital discharge.

PMID- 24871569
TI  - Teduglutide for the Treatment of Short Bowel Syndrome.
AB  - OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical efficacy, and
      safety of the newly approved drug, teduglutide, for the treatment of short bowel
      syndrome (SBS). DATA SOURCES: Literature was retrieved through PubMed (1966-March
      2014) using the search term teduglutide. The authors applied the filters Humans
      and English language, resulting in 47 publications. STUDY SELECTION AND DATA
      EXTRACTION: The authors reviewed the 47 citations to extract those that were
      published clinical trials. Bibliographies of recent review articles and
      editorials were evaluated for additional pertinent publications for inclusion.
      The methods and results from each of the trials were extracted. DATA SYNTHESIS:
      Teduglutide has been studied in SBS in 3 phase III trials. Teduglutide decreases
      parenteral nutrition (PN) volume requirements, with 1 study showing a reduction
      of 4.4 +/- 3.8 L/wk with teduglutide 0.05 mg/kg versus 2.3 +/- 2.7 L/wk with
      placebo; P < 0.001. In another study, teduglutide improved graded response
      scores, which are based on the intensity and duration of the reduction of PN use
      (16/35 assigned to teduglutide 0.05 mg/kg vs 1/16 assigned to placebo; P =
      0.007). The dosing range studies have indicated that the optimal dose of
      teduglutide is 0.05 mg/kg daily subcutaneously. There are a number of adverse
      effects reported in the trials, including abdominal pain or distention, injection
      site reactions, nausea, headaches, and fluid overload among others. There is also
      a concern for the development of malignancy with teduglutide, and therefore, it
      is not recommended in patients with active gastrointestinal malignancies.
      CONCLUSIONS: Overall, teduglutide appears to be a promising agent for the
      treatment of SBS.

PMID- 24871570
TI  - Outcome of singleton preterm small for gestational age infants born to mothers
      with pregnancy-induced hypertension. A population-based study.
AB  - BACKGROUND: Pregnancy-induced hypertension (PIH) has been associated with a
      decreased risk of infant mortality in small for gestational age (SGA) preterm
      infants. OBJECTIVE: To evaluate the influence of PIH on mortality and major
      neonatal morbidities in singleton preterm SGA infants, in the presence and
      absence of acute pregnancy complications. METHODS: Population-based observational
      study of singleton SGA infants, born at 24 to 32 weeks gestation in the period
      1995-2010 (n = 2139). Multivariable logistic regression analyses were used to
      assess the independent effect of PIH on mortality and neonatal morbidities. Acute
      pregnancy complications comprised premature labor, premature rupture of membranes
      >6 h, antepartum hemorrhage and clinical chorioamnionitis. RESULTS: In the
      absence of pregnancy complications, the odds ratio (95% confidence interval) for
      mortality (0.77; 0.50-1.16), survival without severe neurological morbidity
      (1.14; 0.79-1.65) and survival without bronchopulmonary dysplasia (BPD) (0.85;
      0.59-1.21) were similar in the PIH versus no-PIH groups. In the presence of
      pregnancy complications, mortality (0.76; 0.40-1.44), survival without severe
      neurological morbidity (1.16; 0.64-2.12) and survival without BPD (1.04; 0.58
      1.86) were also similar in the PIH versus no-PIH groups. CONCLUSIONS: PIH was not
      associated with improved outcome in preterm SGA infants, both in the presence and
      absence of acute pregnancy complications.

PMID- 24871571
TI  - Differences in peripartal plasma parameters related to calcium homeostasis of
      dairy sheep and goats in comparison with cows.
AB  - Recently it has been demonstrated that there are differences between sheep and
      goats in respect to adaptation to a calcium-restricted diet. It was the aim of
      the present study to evaluate whether species-specific peculiarities also occur
      when calcium homoeostasis is challenged by lactation. Therefore, we investigated
      the time courses of plasma parameters related to calcium homoeostasis (calcium,
      phosphate, calcitriol, the bone resorption marker CrossLaps and the bone
      formation marker osteocalcin) during the transition period in multiparous animals
      of both species and compared the results to data from a former study carried out
      with dairy cows. As in cows, plasma calcium and the ratio of bone formation to
      bone resorption decreased at parturition in goats while plasma calcitriol
      increased. On day 10 post partum the bone parameters of goats reached prepartum
      values again, which was not the case in cows. Sheep were found to experience a
      challenge of calcium homoeostasis already 10 d before parturition, reflected by a
      very low ratio of bone formation to bone resorption, which was not accompanied by
      an increase in plasma calcitriol. Additionally, sheep and goats which had been in
      milk for 3 months were sampled, dried-off and sampled again 6 weeks later. In
      dried-off animals there were no detectable differences in parameters of bone
      metabolism. In conclusion we could show that the contribution of bone
      mobilisation to the compensation for the enhanced calcium demand due to lactation
      differs between the three ruminant species.

PMID- 24871572
TI  - Anti-inflammatory and antipruritic effects of luteolin from Perilla (P.
      frutescens L.) leaves.
AB  - Perilla (Perilla frutescens L.) leaves have shown therapeutic efficacy in the
      treatment of inflammatory disorders, allergies, bronchial asthma, and systemic
      damage due to free radicals. In the present study we analyzed the active
      constituents in perilla leaves using high-performance liquid chromatography
      (HPLC) and isolated luteolin, a polyphenolic flavonoid. We investigated the anti
      inflammatory and antipruritic properties of luteolin. Luteolin inhibited the
      secretion of inflammatory cytokines such as interleukin-1beta (IL-1 beta) and
      tumor necrosis factor-alpha (TNF-alpha) from human mast cells (HMC-1) stimulated
      with phorbol myristate acetate plus calcium ionophore A23187 in a dose-dependent
      manner. Luteolin also significantly reduced the histamine release from rat
      peritoneal mast cells stimulated by compound 48/80, a potent histamine liberator.
      Furthermore, the administration of luteolin markedly inhibited the scratching
      behavior and vascular permeability induced by pruritogens, such as compound 48/80
      or serotonin, in ICR mice. These results suggested that luteolin has potential as
      a therapeutic agent against inflammation and itch-related skin diseases. 

PMID- 24871573
TI  - Optimized solid phase-assisted synthesis of dendrons applicable as scaffolds for
      radiolabeled bioactive multivalent compounds intended for molecular imaging.
AB  - Dendritic structures, being highly homogeneous and symmetric, represent ideal
      scaffolds for the multimerization of bioactive molecules and thus enable the
      synthesis of compounds of high valency which are e.g., applicable in radiolabeled
      form as multivalent radiotracers for in vivo imaging. As the commonly applied
      solution phase synthesis of dendritic scaffolds is cumbersome and time-consuming,
      a synthesis strategy was developed that allows for the efficient assembly of acid
      amide bond-based highly modular dendrons on solid support via standard Fmoc solid
      phase peptide synthesis protocols. The obtained dendritic structures comprised up
      to 16 maleimide functionalities and were derivatized on solid support with the
      chelating agent DOTA. The functionalized dendrons furthermore could be
      efficiently reacted with structurally variable model thiol-bearing bioactive
      molecules via click chemistry and finally radiolabeled with 68Ga. Thus, this
      solid phase-assisted dendron synthesis approach enables the fast and
      straightforward assembly of bioactive multivalent constructs for example
      applicable as radiotracers for in vivo imaging with Positron Emission Tomography
      (PET). 

PMID- 24871574
TI  - Novel gram-scale production of enantiopure R-sulforaphane from Tuscan black kale
      seeds.
AB  - Dietary R-sulforaphane is a highly potent inducer of the Keap1/Nrf2/ARE pathway.
      Furthermore, sulforaphane is currently being used in clinical trials to assess
      its effects against different tumour processes. This study reports an efficient
      preparation of enantiopure R-sulforaphane based on the enzymatic hydrolysis of
      its natural precursor glucoraphanin. As an alternative to broccoli seeds, we have
      exploited Tuscan black kale seeds as a suitable source for gram-scale production
      of glucoraphanin. The defatted seed meal contained 5.1% (w/w) of glucoraphanin
      that was first isolated through an anion exchange chromatographic process, and
      then purified by gel filtration. The availability of glucoraphanin (purity~95%,
      weight basis) has allowed us to develop a novel simple hydrolytic process
      involving myrosinase (EC 3.2.1.147) in a biphasic system to directly produce R
      sulforaphane. In a typical experiment, 1.09 g of enantiopure R-sulforaphane was
      obtained from 150 g of defatted Tuscan black kale seed meal.

PMID- 24871579
TI  - Prevention of hypoxic pulmonary hypertension by hypoxia-inducible expression of
      p27 in pulmonary artery smooth muscle cells.
AB  - Hypoxia-induced proliferation of pulmonary artery smooth muscle cells (SMCs) is
      important in the development of hypoxic pulmonary hypertension (HPH). We
      constructed a lentivirial vector containing a smooth muscle-specific promoter and
      six copies of hypoxia response element to co-drive the expression of p27, the key
      cyclin-dependent kinase inhibitor that blocks the G1 to S phase transition in
      cell cycle progression, in pulmonary artery SMCs in hypoxia. Then in vivo we
      examined the prevention effects of the vector on HPH in mice and in vitro the
      specificity on the hypoxia-inducible expression of p27 in pulmonary artery SMCs.
      Hypobaric hypoxia for 4 weeks resulted in significant increases in the right
      ventricular systolic pressure, the ratio of right ventricle to left ventricle
      plus septal weight and the muscularization of pulmonary vessels in mice.
      Administration of the vector before hypoxia significantly prevented the effects
      of hypoxia. In vitro, the vector exhibited hypoxic inducibility and relatively
      specific expression in pulmonary artery SMCs, inhibited the hypoxia-induced
      proliferation of pulmonary artery SMCs and arrested more cells at G0/G1 phase.
      These results demonstrate that the hypoxia-inducible p27 expression prevents the
      development of HPH in mice. 

PMID- 24871580
TI  - In vivo targeted delivery of CD40 shRNA to mouse intestinal dendritic cells by
      oral administration of recombinant Sacchromyces cerevisiae.
AB  - Short hairpin RNA (shRNA)-mediated gene regulation is a commonly used technique
      for gene manipulation. An efficient and safe delivery system is indispensable
      when shRNA is delivered into living organisms for gene therapy. Previous studies
      have proved that DNA and protein can be delivered into dendritic cells (DCs) by
      non-pathogenic Saccharomyces cerevisiae without being degraded. CD40 is closely
      related to apoptosis of tumor cells and some immune mechanisms. In this study, we
      demonstrated that recombinant yeast S. cerevisiae efficiently delivered the shRNA
      of immune-associated gene (CD40) into mouse intestinal DCs via oral
      administration. Western blot analysis of isolated intestinal DCs indicated that
      the inhibition of CD40 gene expression reached up to 56-91%. The secretion of
      cytokines such as interleukin-2 (IL-2), IL-6, IL-10, IL-12, tumor necrosis factor
      alpha and interferon-gamma in intestinal DCs had varying degrees of changes. In
      conclusion, we found that orally administered recombinant yeast can be used as an
      efficient shRNA delivery system for intestinal DC-specific gene silencing and
      immunomodulation in vivo. 

PMID- 24871582
TI  - Male breast cancer: clinical-epidemiological characteristics of 1189 Brazilian
      patients.
AB  - PURPOSE: To describe the clinical-epidemiological features of male patients with
      breast cancer in Brazil. METHODS: Data from male patients with breast cancer
      treated from 2000 through 2009 were obtained from the Brazilian Hospital Cancer
      Register databases. Descriptive statistics were performed. RESULTS: A total of
      1189 male patients were included. The mean age at diagnosis was 59.6 years (+/-
      13.6). Tumours were categorised as clinical stage I (14.3%), stage II (38.3%),
      stage III (34.1%) and stage IV (13.3%). The most frequent histological type was
      invasive ductal carcinoma (83.7%). The first course treatment (alone or combined)
      consisted of chemotherapy in 53.2%, surgery in 49.2, radiation therapy in 36.8
      and hormonal therapy in 21.0%; 3.4% of cases did not receive treatment. Treatment
      modality varies according to the tumor-node-metastasis (TNM) stage. The
      inadequate response rate was 15.9%, and 7.4% of patients died after the first
      course of treatment. Adequate response according to the first-course cancer
      treatment, after adjusted for clinical stage, was associated with being Caucasian
      (odds ratio (OR) = 2.50; 95% confidence interval (95% CI): 1.35-4.65) and
      submitted to chemotherapy (OR = 0.46; 95% CI: 0.28-0.74). CONCLUSIONS: Male
      breast cancer diagnosis is often made in the advanced stage. Consequently,
      patients were subjected to more aggressive treatments, with poorer clinical
      response.

PMID- 24871581
TI  - Long-term functional duration of immune responses to HCV NS3/4A induced by DNA
      vaccination.
AB  - We have investigated the ability of hepatitis C virus non-structural (NS) 3/4A
      DNA-based vaccines to activate long-term cell-mediated immune responses in mice.
      Wild-type and synthetic codon optimized (co) NS3/4A DNA vaccines have previously
      been shown to be immunogenic in mice, rabbits and humans, although we have very
      poor knowledge about the longevity of the immune responses primed. We therefore
      analyzed the functionality of primed NS3/4A-specific immune responses in BALB/c
      (H-2(d)) and/or C57BL/6J (H-2(b)) mice 1, 2, 3, 4, 6, 12 and 16 months after the
      last immunization. Mice were immunized one, two, three or four times using gene
      gun delivery to the skin or by intramuscular administration. Immunological
      responses after immunization were monitored by protection against in vivo
      challenge of NS3/4A-expressing syngeneic tumor cells. In addition, functionality
      of the NS3/4A-specific T cells was analyzed by a standard cytotoxicity assay.
      First, we identified a new unique murine H-2(d)-restricted NS3/4A cytotoxic T
      lymphocyte (CTL) epitope, which enabled us to study the epitope-specific immune
      responses. Our results show that the coNS3/4A vaccine was highly immunogenic by
      determination of interferon-gamma/tumor necrosis factor-alpha production and
      lytic cytotoxic T cells, which could efficiently inhibit in vivo tumor growth.
      Importantly, we showed that one to four monthly immunizations protected mice from
      tumor development when challenged up to 16 months after the last immunization.
      When determining the functionality of NS3/4A-specific T cells in vitro, we showed
      detectable lytic activity up to 12 months after the last immunization. Thus,
      NS3/4A-based DNA vaccines activate potent cellular immune responses that are
      present and function in both BALB/c and C57BL/6J mice up to 12-16 months after
      the last immunization. The induction of long-term immunity after NS3/4A DNA
      immunization has not been shown previously and supports the use of NS3/4A in
      hepatitis C virus vaccine compositions.

PMID- 24871583
TI  - The angiogenic biomarker endocan is upregulated in proliferative diabetic
      retinopathy and correlates with vascular endothelial growth factor.
AB  - PURPOSE/AIM: Endocan is a proteoglycan specifically secreted by endothelial
      cells, is a marker of angiogenesis and endothelial cell activation in response to
      proangiogenic signals. The aim of this study was to measure the levels of endocan
      in the vitreous fluid from patients with proliferative diabetic retinopathy (PDR)
      and to correlate its levels with clinical disease activity and the levels of the
      angiogenic biomarkers vascular endothelial growth factor (VEGF), soluble vascular
      endothelial-cadherin (sVE-cadherin) and soluble endoglin (sEng). In addition, we
      investigated the expression of endocan and correlated it with the level of
      vascularization in PDR epiretinal membranes. MATERIALS AND METHODS: Vitreous
      samples from 44 PDR and 29 non-diabetic patients were studied by enzyme-linked
      immunosorbent assay. Epiretinal membranes from 14 patients with PDR were studied
      by immunohistochemistry. RESULTS: Endocan, VEGF, sVE-cadherin and sEng levels
      were significantly higher in PDR patients than in non-diabetic patients (p <
      0.001; p = 0.002; p < 0.001; p = 0.001, respectively). Endocan levels were
      significantly higher in patients with active PDR than in patients with inactive
      PDR and non-diabetic patients (p < 0.001). There were significant positive
      correlations between endocan levels and the levels of VEGF (r = 0.574, p < 0.001)
      and sVE-cadherin (r = 0.498, p < 0.001). In epiretinal membranes, vascular
      endothelial cells and myofibroblasts expressed endocan. There was a significant
      positive correlation between the number of blood vessels expressing CD34 and the
      number of blood vessels expressing endocan (r = 0.933, p < 0.001). CONCLUSIONS:
      Our findings suggest that upregulation of endocan expression in PDR could be a
      reflection of endothelial cell activation associated with angiogenesis.

PMID- 24871584
TI  - Lipid nanocapsules functionalized with polyethyleneimine for plasmid DNA and drug
      co-delivery and cell imaging.
AB  - The paper reports on the preparation of lipid nanocapsules (LNCs) functionalized
      with poly(ethyleneimine) (PEI) moieties and their successful use as drug and gene
      delivery systems. The cationic LNCs were produced by a phase inversion process
      with a nominal size of 25 nm and subsequently modified with PEI chains using a
      transacylation reaction. The functionalization process allowed good control over
      the nanoscale particle size (26.2 +/- 3.9 nm) with monodisperse size
      characteristics (PI < 0.2) and positive surface charge up to +18.7 mV. The PEI
      modified LNCs (LNC25-T) displayed good buffering capacity. Moreover, the cationic
      LNC25-T were able to condense DNA and form complexes via electrostatic
      interactions in a typical weight ratio-dependent relationship. It was found that
      the mean diameter of LNC25-T/pDNA complexes increased to ~40-50 nm with the LNC25
      T/pDNA ratio from 1 to 500. Gel electrophoresis and cell viability experiments
      showed that the LNC25-T/pDNA complexes had high stability with no cytotoxicity
      due to the anchored PEI polymers on the surface of LNCs. Finally, the
      transfection efficiency of the LNC25-T/pDNA complexes was studied and evaluated
      on HEK cell lines in comparison with free PEI/pDNA polyplexes. The combination of
      cationic LNCs with pDNA exhibited more than a 2.8-fold increase in transfection
      efficiency compared to the standard free PEI/pDNA polyplexes at the same PEI
      concentrations. Moreover, we have demonstrated that LNC25-T/pDNA loaded with a
      hydrophobic drug, paclitaxel, showed high drug efficacy. The high transfection
      efficiency combined with the potential of simultaneous co-delivery of hydrophobic
      drugs, relatively small size of LNC25-T/pDNA complexes, and fluorescence imaging
      can be crucial for gene therapy, as small particle sizes may be more favorable
      for in vivo studies. 

PMID- 24871585
TI  - Dynamic rearrangement of bilayers of porphyrin hetero-dimers at a solid/liquid
      interface.
AB  - STM reveals that self-assembled bilayers of covalently linked Cu-Mn porphyrin
      dimers can dynamically rearrange at a solid/liquid interface by rapid exchange of
      molecules between the bilayer and the supernatant, or via a slower two
      dimensional translation of the whole top layer. 

PMID- 24871586
TI  - Acidic pH weakens the microhardness and microstructure of three tricalcium
      silicate materials.
AB  - AIM: To investigate the microhardness and microstructural features of three
      tricalcium silicate materials: mineral trioxide aggregate (MTA), Endosequence
      Root Repair Material Putty (ERRM Putty) and Endosequence Root Repair Material
      Paste (ERRM Paste), after exposure to a range of acidic environments in
      comparison with intermediate restorative material (IRM). METHODOLOGY:
      Endosequence Root Repair Material Putty (Brasseler, Savannah, GA, USA), ERRM
      Paste (Brasseler, Savannah, GA, USA), MTA (ProRoot; Dentsply Tulsa Dental,
      Johnson City, TN, USA) and IRM (Dentsply Caulk, Milford, DE, USA) were set in
      cylindrical rubber moulds as four groups containing twenty specimens each.
      Fifteen specimens per each material were randomly distributed into three groups
      (n = 5) to be exposed to butyric acid buffered at three different pH levels (5.4,
      6.4 and 7.4) for 7 days. The remaining five specimens were exposed to distilled
      water as a control group. The surface microhardness after exposure either to acid
      or to water was measured after 7-days at 37  degrees C. The morphology of the
      internal microstructure was observed using a scanning electron microscope (SEM).
      Two-way univariate analysis of variance (anova) was applied to evaluate the
      Vickers microhardness value (VHN). RESULTS: The microhardness values of the
      materials were significantly higher in the neutral environment of butyric acid at
      pH 7.4 compared to those in the acidic condition of pH 5.4 for all groups (P <
      0.001). MTA, ERRM Putty and ERRM Paste had higher microhardness values than IRM
      at all pH levels (P < 0.001). Specimens exposed to distilled water displayed
      significantly higher microhardness values than those values obtained in the
      presence of butyric acid buffered to all pH levels (P < 0.001). A more porous
      microstructure was observed following exposure to butyric acid at pH 5.4 than at
      pH 7.4. Several types of crystalline structures were formed by recrystallization,
      especially at pH 7.4 in all groups except for IRM. CONCLUSIONS: The microhardness
      values of ERRM Putty, ERRM Paste and MTA were reduced in an acidic environment,
      which resulted in these materials having more porous and less crystalline
      microstructures. MTA seems the most suitable material for application to an area
      of inflammation where a low pH value may exist.

PMID- 24871589
TI  - Cleavage of cytoplasm within the oligonucleate zoosporangia of allomyces
      macrogynus.
AB  - Allomyces macrogynus produces zoosporangia that discharge uninucleate zoospores
      after cleavage of multinucleate cytoplasm. Cleavage of cytoplasm within the
      oligonucleate zoosporangia of A. macrogynus was visualized by constructing three
      dimensional models based on electron micrographs and confocal images. In
      oligonucleate zoosporangia, three adjacent nuclei can form three cleavage planes
      with a line of intersection of the planes. The position and boundary of the
      cleavage planes are thought to be determined by the relative positions of the
      nuclei. The establishment of three cleavage planes by cleavage membranes occurred
      sequentially, and the nuclear axis connecting the centers of two nuclei affected
      the development of cleavage membranes on each cleavage plane. In multinucleate
      zoosporangia, groups of three neighboring nuclei near the cell cortex may
      initiate the sequential establishment of cleavage planes and then may interact
      with the nuclei further from the cortex until the interactions of nuclei are
      propagated to the central region of the cytoplasm. 

PMID- 24871590
TI  - Four new species in Magnaporthaceae from grass roots in New Jersey Pine Barrens.
AB  - Based on morphology and DNA sequences of SSU, ITS, LSU, MCM7, RPB1 and TEF1
      genes, we describe four new species in Magnaporthaceae that are associated with
      grass roots collected from New Jersey Pine Barrens. A new genus,
      Pseudophialophora, is erected to accommodate three species, which is
      characterized by slow growth on potato dextrose agar, curved conidiogenous cells
      without a conspicuous collarette at the apex and oblong ellipsoidal conidia.
      Pseudophialophora eragrostis, P. panicorum and P. schizachyrii are assigned to
      this genus. A new species of Magnaporthiopsis also is reported and named as M.
      panicorum. Distinctions between them and phylogenetic relationships with other
      Magnaporthaceae taxa are discussed. 

PMID- 24871587
TI  - Gingival abrasion and recession in manual and oscillating-rotating power brush
      users.
AB  - OBJECTIVE: To assess gingival recession (GR) in manual and power toothbrush users
      and evaluate the relationship between GR and gingival abrasion scores (GA).
      METHODS: This was an observational (cross-sectional), single-centre, examiner
      blind study involving a single-brushing exercise, with 181 young adult
      participants: 90 manual brush users and 91 oscillating-rotating power brush
      users. Participants were assessed for GR and GA as primary response variables.
      Secondary response variables were the level of gingival inflammation, plaque
      score reduction and brushing duration. Pearson correlation was used to describe
      the relationship between number of recession sites and number of abrasions.
      Prebrushing (baseline) and post-brushing GA and plaque scores were assessed and
      differences analysed using paired tests. Two-sample t-test was used to analyse
      group differences; ancova was used for analyses of post-brushing changes with
      baseline as covariate. RESULTS: Overall, 97.8% of the study population had at
      least one site of >=1 mm of gingival recession. For the manual group, this
      percentage was 98.9%, and for the power group, this percentage was 96.7% (P =
      0.621). Post-brushing, the power group showed a significantly smaller GA increase
      than the manual group (P = 0.004); however, there was no significant correlation
      between number of recession sites and number of abrasions for either group (P >=
      0.327). CONCLUSIONS: Little gingival recession was observed in either toothbrush
      user group; the observed GR levels were comparable. Lower post-brushing gingival
      abrasion levels were seen in the power group. There was no correlation between
      gingival abrasion as a result of brushing and the observed gingival recession
      following use of either toothbrush.

PMID- 24871591
TI  - Peltaster cerophilus is a new species of the apple sooty blotch complex from
      Europe.
AB  - Adopting the currently used concept for the genus Peltaster, the sooty blotch
      fungus Peltaster cerophilus is newly described from the cuticle of ripening or
      ripe apples. It forms a punctate phenotype consisting of superficially formed
      pycnothyria and a superficial mycelial mat consisting of a net of brown or
      brownish black hyphae. The pycnothyria are olivaceous brown to brown but have a
      spot in the center that is less strongly pigmented. Pycnothyria on the holotype
      of P. fructicola are homogeneously pigmented. On synthetic nutrient-poor agar, P.
      cerophilus is largely indistinguishable from P. fructicola. It forms delicate,
      spreading hyphae and intercalary conidiogenous cells with short, lateral,
      apically thick-walled conidiogenous necks forming blastic, unpigmented, one
      celled conidia in basipetal succession. Conidia can swell and become one-septate.
      The species has microcyclical conidiation in proximate parts of colonies. DNA
      sequence analyses based on the ITS and the partial nuclear small and large
      subunit ribosomal RNA genes, the partial mitochondrial small subunit rRNA gene
      and the partial translation elongation factor 1-alpha gene support the
      distinction of the European P. cerophilus from P. fructicola, which is known from
      North America and Europe. The nuclear small ribosomal RNA subunit gene sequences
      of P. cerophilus contain two group I introns at locations known to accommodate
      introns in certain other, unrelated taxa. One of these, for which the code "SSU
      1506 intron" was adopted, is 1459 base pairs long and located between the
      universal primer sites ITS5 and ITS1. Similar or positional-differing introns
      were encountered also in three currently undescribed Peltaster species.
      Representative strains of Peltaster fructicola did not accommodate introns in the
      nuclear small subunit ribosomal RNA gene. 

PMID- 24871592
TI  - Exobasidium maculosum, a new species causing leaf and fruit spots on blueberry in
      the southeastern USA and its relationship with other Exobasidium spp. parasitic
      to blueberry and cranberry.
AB  - Exobasidium leaf and fruit spot of blueberry (Vaccinium section Cyanococcus) is
      an emerging disease that has rapidly increased in prevalence throughout the
      southeastern USA. To determine whether this disease is caused by a new species of
      Exobasidium, we studied the morphology and phylogenetic relationship of the
      causal fungus compared with other members of the genus, including the type
      species E. vaccinii and other species that parasitize blueberry and cranberry (V.
      macrocarpon). Both scanning electron microscopy and light microscopy were used
      for morphological characterization. For phylogenetic analyses, we sequenced the
      large subunit of the rDNA (LSU) from 10 isolates collected from leaf or fruit
      spots of rabbiteye blueberry (V. virgatum), highbush blueberry (V. corymbosum)
      and southern highbush blueberry (Vaccinium interspecific hybrid) from Georgia and
      North Carolina and six isolates from leaf spots of lowbush blueberry (V.
      angustifolium) from Maine and Nova Scotia, Canada. LSU was sequenced from
      isolates causing red leaf disease of lowbush blueberry and red leaf spot (E.
      rostrupii) and red shoot (E. perenne) of cranberry. In addition, LSU sequences
      from GenBank, including sequences with high similarity to the emerging parasite
      and from Exobasidium spp. parasitizing other Vaccinium spp. and related hosts,
      were obtained. All sequences were aligned and subjected to phylogenetic analyses.
      Results indicated that the emerging parasite in the southeastern USA differs
      morphologically and phylogenetically from other described species and is
      described herein as Exobasidium maculosum. Within the southeastern USA,
      clustering based on host species, host tissue type (leaf or fruit) or geographic
      region was not detected; however, leaf spot isolates from lowbush blueberry were
      genetically different and likely represent a unique species. 

PMID- 24871593
TI  - Tranzschelia in the Americas revisited: two new species and notes on the
      Tranzschelia thalictri complex.
AB  - Two new species of Tranzschelia (Pucciniales) are described from the Americas.
      Tranzschelia pseudofusca is a microcyclic species on Anemone spp. (Ranunculaceae)
      with North American distribution. T. mexicana on Prunus salicifolia (Rosaceae) is
      found in Colombia, Ecuador and Mexico. It is assumed that T. mexicana is a
      macrocyclic host-alternating species. T. thalictri, a holarctic microcyclic
      species, has variable morphology and probably is an aggregate of related species.
      Specimens are documented with scanning electron microscopy (ESEM) and light
      microscopy including a simple new technique to illuminate urediniospore germ
      pores. Results are discussed with respect to similar species, distribution and
      life-cycle characters. A key for American species on telial hosts is provided. 

PMID- 24871595
TI  - Orphella intropus (Kickxellomycotina), a new insect endosymbiont with an unusual
      perforating holdfast system and other trichomycetes from Italy.
AB  - New data about trichomycetes (arthropod gut endosymbionts) from northern Italy
      (Piedmont [Piemonte] region) are reported, including the description of two new
      species of Harpellales: Glotzia distorta from mayfly nymphs and Orphella intropus
      from stonefly nymphs. The latter species is characterized by a cellular bulbous
      holdfast that perforates the gut lining of its host. Sixteen additional
      geographical records for Italy are provided, including from the Harpellales,
      Harpellomyces eccentricus, Graminella bulbosa, Orphella catalaunica, Pennella
      grassei, Smittium perforatum, Sm. elongatum, Stachylina nana, St. jujuyensis, St
      penetralis and Tectimyces leptophlebiidarum, and from the Amoebidiales,
      Paramoebidium chattoni, P. corpulentum, P. curvum, P. ecdyonuridae, P. hamatum
      and P. inflexum. We provide an emendation of Pennella grassei, a rare,
      incompletely described and poorly illustrated species that was recovered from
      Italy nearly 50 y after its last citation from France. 

PMID- 24871594
TI  - An elusive ectomycorrhizal fungus reveals itself: a new species of Geopora
      (Pyronemataceae) associated with Pinus edulis.
AB  - Species of the genus Geopora are important ectomycorrhizal associates that can
      dominate the communities of some plant taxa, such as pinyon pine (Pinus edulis),
      a widespread tree of the western United States. Several members of the genus
      Geopora are known only from ectomycorrhizal root tips and thus have not been
      described formally. The sporocarps of some Geopora species occur infrequently
      because they depend on wet years for sporulation. In addition, Geopora sporocarps
      can be small and may be hypogeous at some developmental stage, limiting the
      opportunities for describing their morphology. Using molecular and morphological
      data, we have described a new species of fungus, Geopora pinyonensis, which
      produced ascocarps after unusually high precipitation at a northern Arizona site
      in summer 2012. Based on analysis of the ITS and nuLSU regions of the rDNA, G
      pinyonensis is a new species of Geopora. It has small sporocarps and ascospores
      relative to other members of the genus; however, these morphological features
      overlap with other species. Using rDNA data from sporocarps and ectomycorrhizal
      root tips, we show that the sporocarps correspond to an abundant species of
      ectomycorrhizal fungus associated with pinyon pines that is increasing in
      abundance in drought-affected landscapes and may promote drought tolerance. 

PMID- 24871596
TI  - Xylochrysis lucida gen. et sp. nov., a new lignicolous ascomycete
      (Sordariomycetidae) with holoblastic conidiogenesis.
AB  - The monotypic genus Xylochrysis is introduced for a lignicolous perithecial
      ascomycete that possesses golden yellow ascomata with black glabrous necks, a
      three-layered ascomatal wall, persistent paraphyses, and cylindrical, long
      stipitate unitunicate asci with an inamyloid apical annulus, and hyaline,
      ellipsoidal, unicellular ascospores. In culture it produces hyaline conidiophores
      with terminally arranged branches bearing metulae, conidiogenous cells and
      holoblastic conidia. Phylogenetic analysis of two ribosomal (nc18S and nc28S
      rDNA) and one protein-coding (RPB2) gene position this species within the
      Sordariomycetidae but without close ordinal or familial affiliation.
      Morphological and molecular DNA data support the recognition of this new genus
      and suggest that Xylochrysis is most closely related to the genera Ceratolenta,
      Cyanoannulus and Woswasia. 

PMID- 24871597
TI  - PCR amplification of SNP loci from crude DNA for large-scale genotyping of
      oomycetes.
AB  - Similar to other eukaryotes, single nucleotide polymorphism (SNP) markers are
      abundant in many oomycete plant pathogen genomes. High resolution DNA melting
      analysis (HR-DMA) is a cost-effective method for SNP genotyping, but like many
      SNP marker technologies, is limited by the amount and quality of template DNA. We
      describe PCR preamplification of Phytophthora and Peronospora SNP loci from crude
      DNA extracted from a small amount of mycelium and/or infected plant tissue to
      produce sufficient template to genotype at least 10 000 SNPs. The approach is
      fast, inexpensive, requires minimal biological material and should be useful for
      many organisms in a variety of contexts. 

PMID- 24871598
TI  - The host ranges of conifer-associated Tricholoma matsutake, Fagaceae-associated
      T. bakamatsutake and T. fulvocastaneum are wider in vitro than in nature.
AB  - Tricholoma matsutake is the most commercially important edible mushroom in pine
      forests in Japan. Tricholoma bakamatsutake and T. fulvocastaneum, species closely
      related to T. matsutake, occur in Fagaceae forests. We examined ectomycorrhizal
      (EM) formation by these Tricholoma species by in vitro synthesis among seven
      strains (two of T. matsutake, four of T. bakamatsutake, one of T. fulvocastaneum)
      and axenic plants of pine (Pinus densiflora) and oak (Quercus serrata, Q.
      phillyraeoides). All strains, except for one of T. matsutake, formed EM
      associations with both pine and oak. Plant growth and mycelial development were
      differently affected by EM formation depending on the plant-fungus combination. 

PMID- 24871599
TI  - Phytophthora niederhauserii sp. nov., a polyphagous species associated with
      ornamentals, fruit trees and native plants in 13 countries.
AB  - A non-papillate, heterothallic Phytophthora species first isolated in 2001 and
      subsequently from symptomatic roots, crowns and stems of 33 plant species in 25
      unrelated botanical families from 13 countries is formally described here as a
      new species. Symptoms on various hosts included crown and stem rot, chlorosis,
      wilting, leaf blight, cankers and gumming. This species was isolated from
      Australia, Hungary, Israel, Italy, Japan, the Netherlands, Norway, South Africa,
      Spain, Taiwan, Turkey, the United Kingdom and United States in association with
      shrubs and herbaceous ornamentals grown mainly in greenhouses. The most prevalent
      hosts are English ivy (Hedera helix) and Cistus (Cistus salvifolius). The
      association of the species with acorn banksia (Banksia prionotes) plants in
      natural ecosystems in Australia, in affected vineyards (Vitis vinifera) in South
      Africa and almond (Prunus dulcis) trees in Spain and Turkey in addition to
      infection of shrubs and herbaceous ornamentals in a broad range of unrelated
      families are a sign of a wide ecological adaptation of the species and its
      potential threat to agricultural and natural ecosystems. The morphology of the
      persistent non-papillate ellipsoid sporangia, unique toruloid lobate hyphal
      swellings and amphigynous antheridia does not match any of the described species.
      Phylogenetic analysis based on sequences of the ITS rDNA, EF-1alpha, and beta-tub
      supported that this organism is a hitherto unknown species. It is closely related
      to species in ITS clade 7b with the most closely related species being P. sojae.
      The name Phytophthora niederhauserii has been used in previous studies without
      the formal description of the holotype. This name is validated in this manuscript
      with the formal description of Phytophthora niederhauserii Z.G. Abad et J.A.
      Abad, sp. nov. The name is coined to honor Dr John S. Niederhauser, a notable
      plant pathologist and the 1990 World Food Prize laureate. 

PMID- 24871600
TI  - Clarifying the butter Boletes: a new genus, Butyriboletus, is established to
      accommodate Boletus sect. Appendiculati, and six new species are described.
AB  - The butter boletes (Boletus s.l. sect. Appendiculati) are an economically
      important group of ectomycorrhizal fungi whose basidiocarps have a yellow tube
      layer that often bruises blue, yellow reticulate stipe, mild flavor and firm
      yellow-tinged flesh that may or may not turn blue when exposed. Morphological
      characters and molecular data (ITS and LSU) place this group in a separate
      phylogenetic clade from Boletus sensu stricto. Here we establish a new genus,
      Butyriboletus, to accommodate 14 species of butter boletes that range from Asia
      to Europe, north Africa and North America. We recombine eight previously
      described butter bolete species and we describe six new species: four from
      western USA (Bu. persolidus, Bu. primiregius, Bu. autumnigius, Bu. querciregius)
      and two from Yunnan, China (Bu. yicibus, Bu. sanicibus). 

PMID- 24871601
TI  - Validation of the trichomycete Paramoebidium chattoni (Amoebidiales,
      Mesomycetozoea), a common and cosmopolitan black fly endosymbiont.
AB  - Paramoebidium, along with Amoebidium, constitute the Amoebidiales, which is
      phylogenetically embedded within the protist clade Ichthyosporea
      (Mesomycetozoea). However, the order is conventionally included within the
      trichomycetes, an ecological and polyphyletic group of arthropod-gut
      endosymbionts. Paramoebidium chattoni (Leger and Duboscq) Duboscq et al. is
      regarded as nomen nudum because the species was incorrectly published, and its
      taxonomic situation has never been addressed. Thus, P. chattoni is validated here
      with a description and neotypification to formalize the species and to guarantee
      the maintenance and correct use of its name. This common species has a wide
      geographical range and inhabits the digestive system of aquatic black fly larvae,
      where it frequently appears together with other gut endosymbionts, including P.
      curvum. 

PMID- 24871602
TI  - Laboulbenia slackensis and L. littoralis sp. nov. (Ascomycota, Laboulbeniales),
      two sibling species as a result of ecological speciation.
AB  - Laboulbenia littoralis is described from the halobiont Cafius xantholoma
      (Coleoptera, Staphylinidae); it previously was misidentified and not properly
      documented. Morphologically the new species belongs to a group of carabidicolous
      taxa similar to Laboulbenia pedicellata and especially Laboulbenia slackensis. It
      is generally accepted that the specificity of Laboulbeniales is based on their
      need for substances from the host. In this relatively strict context, shifts
      between unrelated hosts are difficult to explain. We present morphological and
      ecological evidence supporting the hypothesis that these fungi are capable of
      shifting between unrelated hosts as long as they share the same habitat.
      Adaptation to a particular environment, combined with a reduced dependence from
      specific nutrients of the host, explains the proposed interfamilial host shift. 

PMID- 24871603
TI  - Aspergillus, its sexual states and the new International Code of Nomenclature.
AB  - The newly adopted International Code of Nomenclature for algae, fungi and plants
      (ICN) demands that dimorphic fungi, in particular those with both sexual and
      asexual names, now bear a single name. Although priority is no longer associated
      with the mode of reproduction, the ICN requires justification for choosing an
      asexual name over an existing sexual one. The phylogenetic approach that made
      dual nomenclature for fungi obsolete can be used to help choose names for large
      groups of fungi that are best known by asexual names. Here we apply this approach
      to one of the largest and most diverse asexual genera, the genus Aspergillus. We
      find that existing sexual names may be given to well supported clades of fungi
      with distinct phenotypes, which include sexual morphology as well as
      physiological attributes associated with xerophily, thermophily and mycotoxin
      production. One group of species important to food production and food safety,
      Aspergillus subgen. Circumdati, lacks a well supported clade; here we propose
      that the name Aspergillus be retained for this group. Recognizing that
      nomenclature has economic and social implications, particularly for old,
      important genera, we discuss the consequences of various scenarios to implement
      the new "one name for one fungus" article in the ICN, showing that our approach
      requires the fewest appeals to the ICN while retaining the name Aspergillus for
      many of the most economically and socially important species. 

PMID- 24871604
TI  - Some new and interesting taxa of Cortinarius subgenus Phlegmacium from the
      European Mediterranean Basin.
AB  - We clarify the taxonomy and nomenclature of several taxa of the genus Cortinarius
      subgenus Phlegmacium. To this aim, we have used a combination of morphological
      and molecular data. The evolutionary relationships of the species were inferred
      by comparison of the nuITS by means of weighted maximum parsimony, maximum
      likelihood and two different types of Bayesian methods (with and without a priori
      alignments). Phylogenetic resolution and support of all or most of the species
      included in this study and their relationships were possible only when including
      the phylogenetic signal from ambiguously aligned regions in weighted maximum
      parsimony analyses (recoded INAASE characters) and when the analysis
      simultaneously optimized alignment and phylogeny (with BAli-phy). Three species
      are described as new, Cortinarius mediterraneensis, C. cistoglaucopus and C.
      palazonianus, and C. olivaecodionysae is proposed for C. dionysae f. olivaceus.
      Descriptions are provided for these taxonomic and nomenclatural novelties, along
      with discussions of morphological and phylogenetic affinities to closely related
      taxa. Scanning microphotographs of the basidiospores are provided for the
      discussed taxa, and color pictures of the basidiomes in their natural habitat are
      provided for C. cistoglaucopus, C. mediterraneensis and C. palazonianus. 

PMID- 24871605
TI  - The effect of temperature on germination of chlamydospores of Phytophthora
      ramorum.
AB  - Mycelium-free chlamydospores of 12 isolates of P. ramorum representing three
      clonal lineages were produced with a method involving incubation in nonsterile
      sand at 20 C in darkness for 30 d. Chlamydospores were incubated on selective
      agar medium at 5, 10, 15, 20, 25 and 30 C and germination assessed after 1, 2, 4,
      6 and 8 d incubation. The optimal temperature for germination based on 8 d
      incubation was 20 C for all three clonal lineages tested (NA1, NA2, EU1). Mean
      germination rates were 2, 21, 44, 67, 32 and 0 percent at 5, 10, 15, 20, 25 and
      30 C respectively for all isolates combined. The highest mean germination rate
      was scored by isolates of the EU1 clonal lineage at 20 C (85%) after 8 d
      incubation However, substantial variation was observed among isolates within each
      clonal lineage. Overall temperatures and days of incubation on which germination
      was assessed isolates of the NA1 clonal lineage had the lowest mean germination,
      even though one isolate had the highest germination of any isolate in any
      lineage. The results indicate that 20 C is the optimal germination temperature
      for P. ramorum chlamydospores and that a great disparity in germination
      percentage can exist within isolates, even within a single clonal lineage. 

PMID- 24871606
TI  - Diversity of Penicillium section Citrina within the fynbos biome of South Africa,
      including a new species from a Protea repens infructescence.
AB  - During a survey of the fynbos biome in the Western Cape of South Africa, 61
      Penicillium species were isolated and nine belong to Penicillium section Citrina.
      Based on morphology and multigene phylogenies, section Citrina species were
      identified as P. cairnsense, P. citrinum, P. pancosmium, P. pasqualense, P.
      sanguifluum, P. sizovae, P. sumatrense and P. ubiquetum. One of the species
      displayed unique phenotypic characters and DNA sequences and is described here as
      P. sucrivorum. Multigene phylogenies consistently resolved the new species in a
      clade with P. aurantiacobrunneum, P. cairnsense, P. miczynksii, P. neomiczynskii
      and P. quebecense. However, ITS, beta-tubulin and calmodulin gene sequences are
      unique for P. sucrivorum and growth rates on various media, the ability to grow
      at 30 C, a positive Ehrlich reaction and the absence of sclerotia on all media
      examined, distinguish P. sucrivorum from all of its close relatives. 

PMID- 24871607
TI  - Phylogenetic relationships of five uncommon species of Lasiosphaeria and three
      new species in the Helminthosphaeriaceae (Sordariomycetes).
AB  - In an ongoing effort to monograph the genus Lasiosphaeria, it is desirable to
      obtain estimates of the phylogenetic relationships for five uncommon species, L.
      coacta, L. munkii, L. punctata, L. sphagnorum and L. stuppea. Three additional
      species previously placed in Lasiosphaeria, Echinosphaeria canescens, Hilberina
      caudata and Ruzenia spermoides, also were included in this study as well as three
      undescribed species. These species were believed to have relations elsewhere
      based on various ambiguous morphological characters, so an independent dataset
      from one or more genes was used to resolve their phylogenetic affinities.
      Sequences from the nuclear ribosomal 28S large subunit (LSU) and beta-tubulin
      genes were generated for these taxa. Maximum likelihood and Bayesian analyses
      indicated these taxa form a well supported monophyletic group with members of the
      Helminthosphaeriaceae and therefore, should be transferred out of Lasiosphaeria.
      Except for Helminthosphaeria gibberosa, Hilberina elegans, Ruzenia spermoides and
      Synaptospora plumbea, all taxa within this clade possess ascomata with distinct
      thick-walled setae. Based on a combination of morphological and molecular data,
      Helminthosphaeria tomaculum, Helminthosphaeria triseptata and Hilberina robusta
      are described as new and four new combinations are proposed: Helminthosphaeria
      ludens, Hel. stuppea, Hilberina punctata and H. sphagnorum. Ten new combinations
      are proposed based on morphological data: Echinosphaeria heterostoma,
      Helminthosphaeria flavocompta, Hel. gibberosa, Hel. heterotricha, Hilberina
      breviseta, H. elegans, H. foliicola, H. meznaensis, H. moseri and H.
      rhynchospora. Lasiosphaeria coacta is placed in synonymy with Hel. ludens and the
      previous transfer of Hilberina munkii is accepted. Synaptospora plumbea was found
      to belong in the family. Illustrations are provided for most
      Helminthosphaeriaceae taxa seen in this study. 

PMID- 24871608
TI  - A ruby-colored Pseudobaeospora species is described as new from material
      collected on the island of Hawaii.
AB  - Pseudobaeospora wipapatiae is described as new based on material collected in
      alien wet habitats on the island of Hawaii. Unique features of this beautiful
      species include deep ruby-colored basidiomes with two-spored basidia, amyloid
      cheilocystidia and a hymeniderm pileipellis with abundant pileocystidia that is
      initially deep ruby in KOH then changes to lilac gray. Phylogenetic analysis of
      nuclear large ribosomal subunit sequence data suggest a close relationship
      between Pseudobaeospora and Tricholoma. BLAST comparisons of internal transcribed
      spacer and 5.8S nuclear ribosomal subunit regions sequence data reveal greatest
      similarity with existing sequences of Pseudobaeospora species. A comprehensive
      description, color photograph, illustrations of salient micromorphological
      features and comparisons with phenetically similar taxa are provided. 

PMID- 24871610
TI  - The role of epigenetics in colorectal cancer.
AB  - Colorectal cancer (CRC) results from a stepwise accumulation of genetic and
      epigenetic alterations that transform the normal colonic epithelium into cancer.
      DNA methylation represents one of the most studied epigenetic marks in CRC, and
      three common epigenotypes have been identified characterized by high,
      intermediate and low methylation profiles, respectively. Combining DNA
      methylation data with gene mutations and cytogenetic alterations occurring in CRC
      is nowadays allowing the characterization of different CRC subtypes, but the
      crosstalk between DNA methylation and other epigenetic mechanisms, such as
      histone tail modifications and the deregulated expression of non-coding RNAs is
      not yet clearly defined. Epigenetic biomarkers are increasingly recognized as
      promising diagnostic and prognostic tools in CRC, and the potential of
      therapeutic applications aimed at targeting the epigenome is under investigation.

PMID- 24871609
TI  - Close Friends' Psychopathology as a Pathway From Early Adversity to Young
      Adulthood Depressive Symptoms.
AB  - Past research has highlighted the negative impact of early adverse experiences on
      childhood social functioning, including friendship selection, and later mental
      health. The current study explored the long-term effects of early adversity on
      young adults' close friends' psychological symptoms and the impact of these close
      friendships on later depressive symptoms. A prospective longitudinal design was
      used to examine 816 youth from a large community-based sample, who were followed
      from birth through age 25. Participants' mothers provided contemporaneous
      information about adversity exposure up to age 5, and participants completed
      questionnaires about their own depressive symptoms at age 20 and in their early
      20s. Youth also nominated a best friend to complete questionnaires about his or
      her own psychopathology at age 20. Individuals who experienced more early
      adversity by age 5 had best friends with higher rates of psychopathology at age
      20. Moreover, best friends' psychopathology predicted target youth depressive
      symptoms 2 to 5 years later. Results indicate that early adversity continues to
      affect social functioning throughout young adulthood and that best friendships
      marked by elevated psychopathology in turn negatively affect mental health.
      Findings have implications for clinical interventions designed to prevent the
      development of depressive symptoms in youth who have been exposed to early
      adversity. 

PMID- 24871611
TI  - Characterizing traditional and chlorine-shared halogen bonds in complexes of
      phosphine derivatives with ClF and Cl2.
AB  - Ab initio MP2/aug'-cc-pVTZ calculations have been carried out on the halogen
      bonded complexes H2XP:ClF and H2XP:Cl2, with X = F, Cl, OH, NC, CN, CCH, CH3, and
      H. H2XP:ClF complexes are stabilized by chlorine-shared halogen bonds with short
      P-Cl and significantly elongated Cl-F distances. H2XP:Cl2 complexes with X = OH
      and CH3 form only chlorine-shared halogen bonds, while those with X = H, NC, and
      CN form only traditional halogen bonds. On the H2FP:Cl2, H2(CCH)P:Cl2, and
      H2ClP:Cl2 potential surfaces small barriers separate two equilibrium structures,
      one with a traditional halogen bond and the other with a chlorine-shared bond.
      The binding energies of H2XP:ClF and H2XP:Cl2 complexes are influenced by the
      electron-donating ability of H2XP and the electron accepting ability of ClF and
      ClCl, the nature of the halogen bond, other secondary interactions, and charge
      transfer interactions. Changes in electron populations on P, F, and Cl upon
      complex formation do not correlate with changes in the chemical shieldings of
      these atoms. EOM-CCSD spin-spin coupling constants for complexes with chlorine
      shared halogen bonds do not exhibit the usual dependencies on distance. (2X)J(P
      F) and (2X)J(P-Cl) for complexes with chlorine-shared halogen bonds do not
      correlate with P-F and P-Cl distances, respectively. (1X)J(P-Cl) values for
      H2XP:ClF correlate best with the Cl-F distance, and approach the values of (1)J(P
      Cl) for the corresponding cations H2XPCl(+). Values of (1X)J(P-Cl) for complexes
      H2XP:ClCl with chlorine-shared halogen bonds correlate with the binding energies
      of these complexes. (1)J(F-Cl) and (1)J(Cl-Cl) for complexes with chlorine-shared
      halogen bonds correlate linearly with the distance between P and the proximal Cl
      atom. In contrast, (2X)J(P-Cl) and (1X)J(P-Cl) for complexes with traditional
      halogen bonds exhibit more normal distance dependencies. 

PMID- 24871612
TI  - Paediatric contrast-enhanced ultrasound (CEUS): a technique that requires co
      operation for rapid implementation into clinical practice.

PMID- 24871613
TI  - Ultrasound of the fetal veins part 1: the intrahepatic venous system.
AB  - Advances in high-resolution ultrasound combined with color Doppler and three
      dimensional (3 D) rendering have contributed to an increasing understanding of
      the fetal venous circulation in recent years. Still the sonographic evaluation of
      the venous system in the fetus remains difficult. This article reviews the normal
      and abnormal intrahepatic venous system. Normal anatomy and abnormal findings of
      the umbilical vein (UV), the ductus venosus (DV), portal veins, hepatic veins and
      the inferior vena cava are demonstrated by grayscale, color Doppler and 3D
      ultrasound and explained by numerous schemes. Typical variants and abnormalities
      such as agenesis of the DV and portal venous system, persistence of the right UV,
      UV varix are explained and the clinical value of normal and abnormal Doppler
      findings in the DV is discussed. Many of these abnormal findings can be detected
      by a targeted examination of the intrahepatic vasculature with means of color
      Doppler.

PMID- 24871615
TI  - Phosphorus removal by steel slag filters: modeling dissolution and precipitation
      kinetics to predict longevity.
AB  - This article presents an original numerical model suitable for longevity
      prediction of alkaline steel slag filters used for phosphorus removal. The model
      includes kinetic rates for slag dissolution, hydroxyapatite and monetite
      precipitation and for the transformation of monetite into hydroxyapatite. The
      model includes equations for slag exhaustion. Short-term batch tests using slag
      and continuous pH monitoring were conducted. The model parameters were calibrated
      on these batch tests and experimental results were correctly reproduced. The
      model was then transposed to long-term continuous flow simulations using the
      software PHREEQC. Column simulations were run to test the effect of influent P
      concentration, influent inorganic C concentration and void hydraulic retention
      time on filter longevity and P retention capacity. High influent concentration of
      P and inorganic C, and low hydraulic retention time of voids reduced the filter
      longevity. The model provided realistic P breakthrough at the column outlet.
      Results were comparable to previous column experiments with the same slag
      regarding longevity and P retention capacity. A filter design methodology based
      on a simple batch test and numerical simulations is proposed. 

PMID- 24871614
TI  - Developmental origins of pregnancy loss in the adult female common marmoset
      monkey (Callithrix jacchus).
AB  - BACKGROUND: The impact of the intrauterine environment on the developmental
      programming of adult female reproductive success is still poorly understood and
      potentially underestimated. Litter size variation in a nonhuman primate, the
      common marmoset monkey (Callithrix jacchus), allows us to model the effects of
      varying intrauterine environments (e.g. nutrient restriction, exposure to male
      womb-mates) on the risk of losing fetuses in adulthood. Our previous work has
      characterized the fetuses of triplet pregnancies as experiencing intrauterine
      nutritional restriction. METHODOLOGY/PRINCIPAL FINDINGS: We used over a decade of
      demographic data from the Southwest National Primate Research Center common
      marmoset colony. We evaluated differences between twin and triplet females in the
      number of pregnancies they produce and the proportion of those pregnancies that
      ended in fetal loss. We found that triplet females produced the same number of
      total offspring as twin females, but lost offspring during pregnancy at a
      significantly higher rate than did twins (38% vs. 13%, p = 0.02). Regardless of
      their own birth weight or the sex ratio of the litter the experienced as fetuses,
      triplet females lost more fetuses than did twins. Females with a male littermate
      experienced a significant increase in the proportion of stillbirths.
      CONCLUSIONS/SIGNIFICANCE: These striking findings anchor pregnancy loss in the
      mother's own fetal environment and development, underscoring a "Womb to Womb"
      view of the lifecourse and the intergenerational consequences of development.
      This has important translational implications for understanding the large
      proportion of human stillbirths that are unexplained. Our findings provide strong
      evidence that a full understanding of mammalian life history and reproductive
      biology requires a developmental foundation.

PMID- 24871617
TI  - Template-assisted nano-patterning of magnetic core-shell particles in gradient
      fields.
AB  - A method is proposed for controlling the assembly of colloidal magnetic core
      shell nanoparticles into patterned monolayer structures with nanoscale feature
      resolution. The method is based on magnetic field-directed self-assembly that is
      enhanced using soft-magnetic template elements. The elements are embedded in a
      nonmagnetic substrate and magnetized using a uniform bias field. A key feature of
      this approach is the combined use of a uniform field with induced gradient-fields
      produced by the template elements. This enables the customization of a force
      field with localized regions of attractive and repulsive magnetic forces that
      provide extraordinary control of particle motion during assembly. The method is
      demonstrated using a computational model that simulates the assembly process
      taking into account magnetic and hydrodynamic forces including interparticle
      interactions, Brownian diffusion, van der Waals force and effects of surfactants.
      The analysis shows that extended geometric patterns of particles can be assembled
      with nanoscale resolution, beyond that of the template elements, within
      milliseconds. This is achieved by tailoring key parameters including the template
      geometry to produce a force field that focuses the particles into prescribed
      patterns; the thickness of the dielectric particle shell to control the magnetic
      dipole-dipole force upon contact and the particle volume fraction to suppress
      undesired aggregation during assembly. The proposed method broadly applies to
      arbitrary template geometries and multi-layered core-shell particles with at
      least one magnetic component. It can enable the self-assembly of complex patterns
      of nanoparticles and open up opportunities for the scalable fabrication of
      multifunctional nanostructured materials for a broad range of applications. 

PMID- 24871616
TI  - Potential for Ultrasonography to Reduce the Cost and Cumulative Radiation Dose in
      Routine Incisional Hernias.

PMID- 24871618
TI  - The genus Cerithidea Swainson, 1840 (Gastropoda: Potamididae) in the Indo-West
      Pacific region.
AB  - Members of the genus Cerithidea are common components of the fauna of mangrove
      forests, tidal swamps and salt marshes in the Indo-West Pacific province, in
      marine and brackish conditions. The snails typically rest on the trunks of trees
      and other vegetation and migrate to the substrate to feed at low tide. In many
      areas mangrove habitats are under threat and some Cerithidea species are
      therefore considered to be endangered. In current taxonomic literature, ten
      species are recognized on the basis of shell morphology. A recently published
      molecular phylogenetic analysis has increased this to fifteen. The present study
      is a systematic account of these fifteen recognized species. Of these, two are
      newly described: C. houbricki and C. andamanensis. The species accounts include
      full synonymies, detailed descriptions of shells based on 621 museum samples,
      descriptions of living animals, distribution records and maps, reviews of habitat
      and ecology, and notes on conservation status. 

PMID- 24871619
TI  - Review of the mite family Pachylaelapidae (Acari: Mesostigmata).
AB  - The family Pachylaelapidae Berlese, 1913 (Acari: Mesostigmata) includes a total
      of 16 valid and adequately described genera, namely Chaetodellus Masan &
      Halliday, 2013, Elaphrolaelaps Berlese, 1910, Mirabulbus Liu & Ma, 2001,
      Neopachylaelaps Masan, 2007, Olopachys Berlese, 1910, Onchodellus Berlese, 1904,
      Pachydellus Masan, 2007, Pachyglobolaelaps Masan, new genus, Pachylaelaps
      Berlese, 1888, Pachylaelapsoides Masan, 2007, Pachyseiulus Moraza & Johnston,
      1990, Pachyseius Berlese, 1910, Pachysphaerolaelaps Masan, 2007, Paralaelaps
      Tragardh, 1908, Pseudopachys Berlese, 1916 and Sphaerolaelaps Berlese, 1903.
      Three of these genera include subgenera, namely Elaphrolaelaps (Incisosternum)
      Elsen, 1974, Olopachys (Olopachylaella) Masan, 2007 and Pachylaelaps
      (Longipachylaelaps) Masan, 2007.The family is classified here into three
      subfamilies, Pachyseiinae Karg, 1971 including Pachyseius and Mirabulbus;
      Pachyseiulinae Masan, 2007 including Pachyseiulus and Pseudopachys; and
      Pachylaelapinae Berlese, 1913, with all the other genera. Pachylaelapinae is
      further divided into three tribes, Pachylaelapini, Paralaelapini and
      Onchodellini. Almost half of the known genera are monotypic: Neopachylaelaps,
      Pachyglobolaelaps, Pachylaelapsoides, Pachyseiulus, Pachysphaerolaelaps,
      Pseudopachys and Sphaerolaelaps, while Onchodellus and Pachylaelaps are the
      largest genera in the family.Eleven genera that were provisionally classified as
      Pachylaelapidae cannot be reliably placed into a family on the basis of the
      available information, or have been incorrectly placed in the Pachylaelapidae:
      Actinoseius Berlese, 1916, Beaurieuia Oudemans, 1929, Brachylaelaps Berlese,
      1910, Bulbogamasus Gu, Wang & Duan, 1991, Megalolaelaps Berlese, 1892,
      Meliponapachys Turk, 1948, Neoparasitus Oudemans, 1901, Pachylaella Berlese,
      1916, Platylaelaps Berlese, 1905, Pseudolaelaps Berlese, 1916 and Zygoseius
      Berlese, 1916.New synonymies are established for Pseudoparasitus (Pseudopachys)
      parasitizans Berlese, 1916 (= Pseudopachyseiulus ignacii Moraza & Johnston, 1993)
      and Pseudopachys Berlese, 1916 (= Pseudopachyseiulus Moraza & Johnston, 1993).
      Brachylaelaps and Pachylaella are here considered as genera of Neoparasitidae and
      Macrochelidae respectively, rather than Pachylaelapidae. The genus Mirabulbus is
      redefined and transferred from Bulbogamasidae to Pachyseiinae. Paralaelaps and
      Elaphrolaelaps are provisionally placed together in the Pachylaelapinae and the
      new tribe Paralaelapini. Altogether 44 new combinations are proposed.Onchodellus
      slovacus Masan and Pachyglobolaelaps hallidayi Masan are introduced as new
      species. Masan (2007a) described these species but did not designate holotypes
      for them, so their names are not available from that date.Replacement names are
      proposed for five junior homonyms: (1) Onchodellus michaelcostai Masan &
      Halliday, replacement name for Pachylaelaps brevis Costa, 1971, junior homonym of
      Pachylaelaps brevis Berlese, 1920; (2) Onchodellus morazae Masan & Halliday,
      replacement name for Pachylaelaps minutus Moraza & Pena, 2005, junior homonym of
      Pachylaelaps minutus Oudemans, 1901; (3) Pachylaelaps atlanticus Masan &
      Halliday, replacement name for Pachylaelaps major Van Driel, Loots & Marais,
      1977, junior homonym of Pachylaelaps (Paralaelaps) major Berlese, 1918; (4)
      Pachylaelaps schweizeri Masan & Halliday, replacement name for Pachylaelaps latus
      Schweizer, 1961, junior homonym of Pachylaelaps (Platylaelaps) latus Berlese,
      1905; and (5) Pachylaelaps similis Masan & Halliday, replacement name for
      Pachylaelaps reticulata Hafez & Nasr, 1982, junior homonym of Pachylaelaps
      (Onchodellus) reticulatus Berlese, 1904.We provide a catalogue of the world
      species of Pachylaelapidae, which includes 253 named species (including
      synonyms), with details of their authorship, synonyms, nomenclatural and
      bibliographic details and generic placement.  

PMID- 24871620
TI  - A taxonomic revision of the genus Edosa Walker, 1886 from China (Lepidoptera,
      Tineidae, Perissomasticinae).
AB  - The genus Edosa Walker, 1886 is revised in China. Of the 31 recognized species,
      23 are described as new: Edosa aurea sp. nov., E. baculiformis sp. nov., E.
      bicolor sp. nov., E. bifurcata sp. nov., E. carinata sp. nov., E. conchata sp.
      nov., E. cornuta sp. nov., E. curvidorsalis sp. nov., E. dentata sp. nov., E.
      digitata sp. nov., E. duoprojecta sp. nov., E. elongata sp. nov., E. eminens sp.
      nov., E. hamata sp. nov., E. longicornis sp. nov., E. minuta sp. nov., E.
      robinsoni sp. nov., E. robustispina sp. nov., E. semicircularis sp. nov., E.
      torta sp. nov., E. truncatula sp. nov., E. uncusella sp. nov., and E. varians sp.
      nov.; Edosa gaedikei nom. nov. is proposed as a replacement name for Edosa
      spinosa Gaedike, 2012, a junior homonym of Edosa spinosa Gaedike, 1984; four
      species are newly recorded for China: E. hendrixella Robinson, 2008, E. crayella
      Robinson, 2008, E. orphnodes (Meyrick, 1911) and E. smithaella Robinson, 2008;
      the female of E. hendrixella is described for the first time. Phylogenetic
      relationships of the Chinese species, except E. malthacopis (Meyrick, 1936), are
      postulated based on 42 morphological characters. The phylogenetic analysis of the
      morphology matrix yielded one most parsimonious tree (length 121 steps, CI =
      0.56, RI = 0.81), based on which seven species-groups are proposed: the
      hemichrysella-group, the subochraceella-group, the pyrochra-group, the
      duoprojecta-group, the eminens-group, the crayella-group and the uncusella-group.
      The whole body structures of the genus are presented and photographs of adults
      and genitalia are provided, along with a key to all the known Chinese species and
      maps to show the distribution of Edosa in China. A world checklist of Edosa is
      given as an appendix, in which 41 new combinations are included. 

PMID- 24871621
TI  - Tenuipalpidae (Acari: Trombidiformes) from Casuarinaceae (Fagales).
AB  - The Tenuipalpidae associated with the Casuarinaceae are reviewed, including one
      new genus, Palpipalpus gen. nov., twelve new species, and seven redescriptions.
      Two new generic records for Australia are established, Pentamerismus and
      Philippipalpus. The new species are: Chaudhripalpus costacola Beard and Seeman
      sp. nov., Crossipalpus gersoni Beard and Seeman sp. nov., Crossipalpus raveni
      Beard and Seeman sp. nov., Magdalenapalpus caperatus Beard and Seeman sp. nov.,
      Magdalenapalpus forsteri Seeman and Beard sp. nov., Pentamerismus sititoris Beard
      and Seeman sp. nov., Pentamerismus hicklingorum Seeman and Beard sp. nov.,
      Pentamerismus wardo Seeman and Beard sp. nov., Palpipalpus hesperius Beard and
      Seeman sp. nov. gen. nov., Philippipalpus flumaquercus Beard and Seeman sp. nov.,
      Philippipalpus belah Beard and Seeman sp. nov., and Philippipalpus nigraquercus
      Seeman and Beard sp. nov.  Meyeraepalpus delfinadae Smiley et al., is reinstated
      based on new material and an analysis of its phylogenetic relationships.
      Crossipalpus muellerianae Smiley et al., Crossipalpus verticillatae Smiley et
      al., and Tegopalpus conicus Womersley are redescribed and rediagnosed from the
      original type specimens and newly collected material; and Chaudhripalpus creelae
      (Smiley et al.), Magdalenapalpus strandtmanni (Smiley et al.) and Philippipalpus
      agohoi Corpuz-Raros are redescribed and rediagnosed from type material only. All
      flat mite species were host-specific. Up to three species of flat mite were
      collected from a single she-oak species. Leg setation and ontogeny are reviewed
      for the taxa studied. A key to Tenuipalpidae from Casuarinaceae is provided. A
      phylogeny of the subfamily Tegopalpinae found the following relationships:
      Meyeraepalpus (Australopalpus, Crossipalpus, Palpipalpus (Magdalenapalpus
      (Philippipalpus (Chaudhripalpus + Tegopalpus)))). Our preliminary analysis of the
      Tegopalpinae suggested the group is monophyletic and its sister group is
      Phytoptipalpus. 

PMID- 24871622
TI  - ICD therapy for primary prevention of sudden cardiac death after Mustard repair
      for d-transposition of the great arteries.
AB  - BACKGROUND: Years and decades after the Mustard atrial switch repair for d
      Transposition of the great arteries, there is a subset of patients at increased
      risk for sudden cardiac death due to ventricular tachyarrhythmias. To date,
      little is known about indications, efficacy and benefit of internal cardioverter
      defibrillator (ICD) therapy indication in these patients. PATIENTS/METHODS: To
      characterize the Mustard patients already treated with an ICD, we conducted a
      single center case control study (n = 41). The charts of all patients after
      Mustard procedure at our institution were systematically reviewed for history,
      echocardiographic findings, arrhythmias, hemodynamics and medication as well as
      ICD discharges and complications. RESULTS: Significant differences between ICD (n
      = 12) and non-ICD patients (n = 29) were found regarding the stage of heart
      failure, need for heart failure medication, QRS duration and left ventricular
      diameter and performance. Inappropriate ICD discharges due to rapidly conducted
      atrial reentrant tachycardia and sensing failure were frequently observed. In 17
      % of our Mustard patients with an ICD, infection of the implantation site
      required surgical revision. All ICD patients were of male gender. CONCLUSION:
      Patients after ICD implantation represent a subgroup among our Mustard patients
      with a more advanced state of cardiac disease. Not only systemic right
      ventricular diameter and performance but also subpulmonary left ventricular
      performance was an important factor predicting the long-term course of these
      patients. Prevention of inappropriate discharges requires decent device
      programming, close monitoring of lead integrity and treatment of atrial
      tachycardias.

PMID- 24871623
TI  - Class-modeling approach to PTR-TOFMS data: a peppers case study.
AB  - BACKGROUND: Proton transfer reaction-mass spectrometry (PTR-MS), in its recently
      developed implementation based on time-of-flight mass spectrometry (PTR-TOFMS),
      was used to rapidly determine the volatile compounds present in fruits of
      Capsicum spp. RESULTS: We analyzed the volatile organic compounds emission
      profile of freshly cut chili peppers belonging to three species and 33 different
      cultivars. PTR-TOFMS data, analyzed with appropriate and advanced multivariate
      class-modeling approaches, perfectly discriminated among the three species (100%
      correct classification in validation set). VIP (variable importance in
      projection) scores were used to select the 15 most important volatile compounds
      in discriminating the species. The best candidates for Capsicum spp. were
      compounds with measured m/z of 63.027, 101.096 and 107.050, which were,
      respectively, tentatively identified as dimethyl sulfide, hexanal and
      benzaldehyde. CONCLUSIONS: Based on the promising results, the possibility of
      introducing multivariate class-modeling techniques, different from the
      classification approaches, in the field of volatile compounds analyses is
      discussed.

PMID- 24871625
TI  - Photochromic-fluorescent-plasmonic nanomaterials: towards integrated three
      component photoactive hybrid nanosystems.
AB  - Silica-coated gold nanorods functionalized with grafted fluorescent and
      photochromic derivatives were synthesized and characterized. Spectroscopic
      investigations demonstrated that cross-coupled interactions between plasmonic,
      photochromic, and fluorescence properties play a major role in such nanosystems,
      depending on the thickness of the silica spacer, leading to multi-signal
      photoswitchability. 

PMID- 24871626
TI  - Fatal Strongyloides hyper-infection in a patient with myasthenia gravis.
AB  - PURPOSE: We report a fatal case of Strongyloides hyper-infection as the result of
      corticosteroid therapy of a patient with myasthenia gravis. CASE PRESENTATION:
      Our patient was a farmer with a past history of living in an endemic area for
      Strongyloides stercoralis in Iran. Hyper-infection was diagnosed during the
      advanced-stage disease by demonstration of enormous number of larvae in the
      direct smears prepared from both the stool and tracheal secretions.
      Unfortunately, despite appropriate anti-parasite therapy, the patient died due to
      respiratory failure. CONCLUSION: We recommend the provision of more awareness in
      high-risk people prior to immunosuppressive therapy, through screening for S.
      stercoralis, even in non-endemic regions.

PMID- 24871627
TI  - Telmisartan exerts sustained blood pressure control and reduces blood pressure
      variability in metabolic syndrome by inhibiting sympathetic activity.
AB  - BACKGROUND: Accumulating evidence on blood pressure (BP) reduction with various
      angiotensin II receptor blockers (ARBs) show that the magnitudes and durations of
      BP control differ across ARBs. However, the mechanism of ARBs is unknown. This
      work was undertaken to compare telmisartan and valsartan in duration of BP
      control, BP variability, and effects on the autonomic nervous system. METHODS:
      Using radiotelemetry combined with spectral analysis with a fast Fourier
      transformation algorithm, we compared the effects of various doses of telmisartan
      and valsartan on BP and its variability during dark (active phase) and light
      (inactive phase) periods over 5 weeks in SHR/NDmcr-cp(+/+)(SHRcp) rats, a model
      of metabolic syndrome. We also compared the effects of these ARBs on autonomic
      nervous system, central oxidative stress, and inflammation in SHRcp rats.
      RESULTS: Telmisartan exerted a longer-lasting BP-lowering effect and greater
      attenuation of BP variability in SHRcp than valsartan. Telmisartan decreased low
      frequency power of systolic BP and increased spontaneous baroreflex gain in SHRcp
      during both the dark and light periods more than valsartan. Telmisartan reduced
      24-hour urinary norepinephrine excretion more than valsartan. Furthermore,
      telmisartan attenuated oxidative stress and the numbers of gp91(phox)-positive
      cells and activated microglia and astrocytes in the rostral ventrolateral medulla
      of SHRcp rats more than valsartan. CONCLUSIONS: The superiority of telmisartan
      over valsartan in sustained BP control and reduction of BP variability was
      attributed to more suppression of sympathetic activity and more improvement of
      baroreceptor reflex. The greater suppression of sympathetic activity by
      telmisartan appeared to be partially mediated by a stronger amelioration of
      central oxidative stress.

PMID- 24871624
TI  - A starring role for microglia in brain sex differences.
AB  - Microglia, the resident innate immune cells in the brain, have long been
      understood to be crucial to maintenance in the nervous system, by clearing
      debris, monitoring for infiltration of infectious agents, and mediating the
      brain's inflammatory and repair response to traumatic injury, stroke, or
      neurodegeneration. A wave of new research has shown that microglia are also
      active players in many basic processes in the healthy brain, including cell
      proliferation, synaptic connectivity, and physiology. Microglia, both in their
      capacity as phagocytic cells and via secretion of many neuroactive molecules,
      including cytokines and growth factors, play a central role in early brain
      development, including sexual differentiation of the brain. In this review, we
      present the vast roles microglia play in normal brain development and how
      perturbations in the normal neuroimmune environment during development may
      contribute to the etiology of brain-based disorders. There are notable
      differences between microglia and neuroimmune signaling in the male and female
      brain throughout the life span, and these differences may contribute to the vast
      differences in the incidence of neuropsychiatric and neurological disorders
      between males and females. 

PMID- 24871628
TI  - Prospective risk factors for increased central augmentation index in men and
      women.
AB  - BACKGROUND: Arterial wave reflections are important determinants of central
      pressure pulsatility and left ventricular afterload. The augmentation index (AIx)
      is the most widely used surrogate of arterial wave reflections. Despite multiple
      cross-sectional studies assessing the correlates of AIx, little prospective data
      exist regarding changes in AIx over time. We aimed to assess the predictors of
      changes in AIx over time in adults from the general population. METHODS: We
      performed radial arterial tonometry assessments a median of 3.18 +/- 0.4 years
      apart on 143 nondiabetic adult participants in the population-based PREVENCION
      study. Central AIx was obtained using the generalized transfer function of the
      Sphygmocor device. RESULTS: Predictors of the change in AIx over time were
      investigated. Among men (n = 67), the change in AIx was predicted by abdominal
      obesity (standardized beta for waist circumference = 0.34; P = 0.002), impaired
      fasting glucose (standardized beta = 0.24; P = 0.009), and the change in heart
      rate (standardized beta = -0.78; P < 0.001). Among women (n = 76), the change in
      AIx was predicted by non-high-density lipoprotein cholesterol (standardized beta
      = 0.33; P = 0.001), C-reactive protein levels (standardized beta = 0.24; P =
      0.02), change in mean arterial pressure (standardized beta = 0.33; P = 0.001),
      and change in heart rate (standardized beta = -0.52; P < 0.001). CONCLUSIONS:
      Metabolic and inflammatory factors predicted changes in AIx over time, with
      important sex differences. Metabolic factors, such as abdominal obesity and
      impaired fasting glucose, predicted changes in AIx in men, whereas C-reactive
      protein and non-high-density lipoprotein cholesterol levels predicted changes in
      women. Our findings highlight the impact of sex on arterial properties and may
      guide the design of interventions to favorably impact changes in late systolic
      pressure augmentation.

PMID- 24871629
TI  - Vascular induction of a disintegrin and metalloprotease 17 by angiotensin II
      through hypoxia inducible factor 1alpha.
AB  - BACKGROUND: A disintegrin and metalloprotease 17 (ADAM17) is a membrane-spanning
      metalloprotease overexpressed in various cardiovascular diseases such as
      hypertension and atherosclerosis. However, little is known regarding the
      regulation of ADAM17 expression in the cardiovascular system. Here, we test our
      hypothesis that angiotensin II induces ADAM17 expression in the vasculature.
      METHODS: Cultured vascular smooth muscle cells were stimulated with 100 nM
      angiotensin II. Mice were infused with 1 MUg/kg/minute angiotensin II for 2
      weeks. ADAM17 expression was evaluated by a promoter-reporter construct,
      quantitative polymerase chain reaction, immunoblotting, and immunohistochemistry.
      RESULTS: In vascular smooth muscle cells, angiotensin II increased ADAM17 protein
      expression, mRNA, and promoter activity. We determined that the angiotensin II
      response involves hypoxia inducible factor 1alpha and a hypoxia responsive
      element. In angiotensin II-infused mice, marked induction of ADAM17 and hypoxia
      inducible factor 1alpha was seen in vasculatures in heart and kidney, as well as
      in aortae, by immunohistochemistry. CONCLUSIONS: Angiotensin II induces ADAM17
      expression in the vasculatures through a hypoxia inducible factor 1alpha
      dependent transcriptional upregulation, potentially contributing to end-organ
      damage in the cardiovascular system.

PMID- 24871630
TI  - Renal nerves: time for reassessment of their role in hypertension?

PMID- 24871631
TI  - Impact of yeast strain on ester levels and fruity aroma persistence during aging
      of Bordeaux red wines.
AB  - The impact of yeast and lactic acid bacteria strains on the fruity aroma of red
      wines was investigated by sensory and analytical strategies. The ester
      composition of four different Bordeaux red wines was quantified by HS-SPME-GC/MS.
      These wines, made with selected yeast and bacteria strains, were investigated at
      the end of alcoholic fermentation and regularly until 12 months of aging, during
      2011 and 2012 vintages. Sensory analyses of wines after 3 and 12 months of aging
      revealed significant differences with regard to yeast strains. Bacteria seemed to
      have only a slight impact on changes in aromatic profile. Ester levels were
      strongly influenced by yeast strain and very little affected by malolactic
      fermentation and aging. Differences and similarities between sensory data and
      ester profile are discussed. This study highlights the importance of yeast
      strains in red winemaking. Their sensory impact remains despite the other
      vinification steps after alcoholic fermentation. 

PMID- 24871632
TI  - Improving tobacco-free advocacy on college campuses: a novel strategy to aid in
      the understanding of student perceptions about policy proposals.
AB  - OBJECTIVE: Tobacco-control policy proposals are usually met with opposition on
      college campuses. Research to understand students' viewpoints about health
      related policy proposals and messaging strategies, however, does not exist. This
      study investigated students' perceptions about a smoke-free policy proposal to
      help understand their positions of support and opposition and to inform the
      development of effective messaging strategies. PARTICIPANTS: In January 2012,
      1,266 undergraduate students from a midwestern university completed an online
      questionnaire about smoke-free campus policies. METHODS: Responses were coded and
      analyzed using Linguistic Inquiry and Word Count software and chi-square,
      independent-samples t tests, and binary logistic models. RESULTS: Most students
      who supported a smoke-free policy considered environmental or aesthetic
      conditions, whereas most opponents used personal freedom frames of thought.
      Supporters viewed smoking policies in personal terms, and opponents suggested
      means-ends policy reasoning. CONCLUSIONS: Taken together, points of reference and
      emotions about proposed policies provided insight about participants'
      perspectives to help inform effective policy advocacy efforts.

PMID- 24871635
TI  - Stability of Z2 topological order in the presence of vacancy-induced impurity
      band.
AB  - Although topological insulators (TIs) are known to be robust against non-magnetic
      perturbations and exhibit edge or surface states as their distinct feature,
      experimentally it is known that vacancies often occur in these materials and
      impose strong perturbations. Here, we investigate effects of vacancies on the
      stability of Z2 topological order using the Kane-Mele (KM) model as a prototype
      of topological insulators. It is shown that even though a vacancy is not
      classified as a topological defect in the KM model, it generally induces a pair
      of degenerate mid-gap bound states only in the TI phase. Hence mid-gap bound
      states due to vacancies arise from the same Z2 classification of topological
      insulators. Furthermore, we show that in the presence of many vacancies, an
      impurity band is induced and coexists with edge states until a phase transition
      occurs when the spectral weights of Dirac cones near Dirac points are depleted.
      Our analyses indicate that the same scenario holds for point vacancies or lines
      of vacancies in 3D TIs as well. 

PMID- 24871633
TI  - Recovery of severe motor deficit secondary to herniated lumbar disc prolapse: is
      surgical intervention important? A systematic review.
AB  - INTRODUCTION: The natural history of motor deficit due to lumbar disc herniation
      has been thought to be favourable. However, on closer analysis of seminal
      articles on this topic, this is not the case for patients with severe motor
      deficits (MRC grade <=3). The aim of this study is to answer the following
      questions: (1) Is surgical intervention beneficial in patients with severe motor
      weakness (defined by MRC grade of 3 or less) due to herniated lumbar nucleus
      pulposus? (2) Does time to surgery from onset of motor weakness influence the
      outcome? (3) Are there any other prognostic factors? MATERIALS AND METHODS: A
      comprehensive search was conducted in MEDLINE and EMBASE from 1970 upto July
      2013. Inclusion criteria for studies are: (1) minimum of three patients aged 18
      and older, who had symptomatic herniated lumbar disc prolapse and underwent
      surgery, (2) description of pre and post-operative muscle weakness utilising the
      Medical Research Council (MRC) muscle power grade or equivalent, such that both
      reviewers could confidently identify a cohort of patients with at least grade
      three motor weakness or worse, (3) a minimum of 6 months follow-up. RESULTS:
      Seven studies were identified with a total of 354 patients. Complete recovery was
      seen in 38.4% of patients following surgery and 32% following non-operative
      treatment. Age and grade of motor deficit were identified as significant
      prognostic factors in some of the studies. CONCLUSION: The current available
      evidence is not robust enough to address the questions posed. We have proposed a
      framework for future studies.

PMID- 24871637
TI  - Diagnostic performance of emergency transthoracic focus cardiac ultrasound in
      suspected acute type A aortic dissection.
AB  - Type A aortic dissection (AD) is a deadly disease. Rapid identification of
      patients requiring immediate advanced aortic imaging or transfer to specialized
      centers is needed to improve outcomes. We evaluated the diagnostic performance of
      transthoracic focus cardiac ultrasound (FOCUS) performed by emergency physicians,
      alone and in combination with the aortic dissection detection (ADD) risk score in
      suspected type A AD. This was a prospective study performed on patients with
      suspected type A AD. FOCUS evaluated the presence of intimal flap/intramural
      hematoma (direct signs of AD), ascending aorta dilatation, aortic valve
      insufficiency or pericardial effusion/tamponade (indirect signs of AD). The ADD
      risk score of each patient was calculated according to guidelines. The final
      diagnosis was established after review of complete clinical data. 50 (18%)
      patients of 281 had a final diagnosis of type A AD. Detection of any FOCUS sign
      (direct or indirect) of AD had a sensitivity of 88% (95% CI 76-95%) for the
      diagnosis of type A AD. Presence of ADD risk score > 0 or detection of any FOCUS
      sign increased diagnostic sensitivity to 96% (95% CI 86-99%). Detection of direct
      FOCUS signs had a specificity of 94% (95% CI 90-97%), while combination of ADD
      risk score > 1 with detection of direct FOCUS signs had a specificity of 98% (95%
      CI 96-99%). FOCUS demonstrated acceptable accuracy as a triage tool to rapidly
      identify patients with suspected type A AD needing advanced aortic imaging or
      transfer, but it cannot be used as a stand-alone test even if combined with ADD
      risk score classification.

PMID- 24871638
TI  - The value of inhibitors of factor Xa for the treatment of pulmonary embolism.
AB  - The introduction of factor Xa inhibitors advocated the initiation of clinical
      trials that addressed the value of anticoagulation in patients with
      hemodynamically stable primary pulmonary embolism (PE). In the Matisse trial in
      patients with PE, fondaparinux administered at therapeutic doses followed by
      vitamin K antagonists (VKA) has shown a comparable efficacy and safety profile to
      that seen with intravenous adjusted-dose unfractionated heparin/VKA. A long
      acting derivative of fondaparinux, idraparinux, failed to achieve similar
      results. On the other hand, the Cassiopea study revealed that once weekly
      injections of idrabiotaparinux, a slightly modified form of idraparinux, have
      similar efficacy and better safety profile compared to VKAs in the long-term
      treatment of patients with PE. However, the inconvenient parenteral
      administration of both fondaparinux and idrabiotaparinux limits their routine
      clinical use. The availability of antithrombotic compounds that can be
      administered orally in fixed dose, owing to their predictable pharmacokinetics
      and pharmacodynamics, and have a lower potential for drug and food interactions
      has opened new horizons for the treatment of patients with PE. The Einstein PE,
      Amplify and Hokusai studies, conducted with rivaroxaban, apixaban and edoxaban,
      respectively, showed that for the treatment of PE they possess a more favorable
      benefit-to-risk profile than the conventional antithrombotic drugs. In addition,
      rivaroxaban and apixaban make it possible to treat uncomplicated PE patients from
      the beginning, without the need for the parenteral administration of heparins or
      fondaparinux, and edoxaban allows the treatment of fragile patients with lower
      doses. All of them cover a wide spectrum of clinical presentations, including PE
      patients at intermediate risk. 

PMID- 24871636
TI  - Identification and management of invasive mycoses in internal medicine: a road
      map for physicians.
AB  - Invasive mycoses are a rising problem, not only in traditional categories of
      patients like hematologic or neutropenic ones, but also in elderly non
      neutropenic patients admitted to internal medicine wards. Patients being admitted
      to medical wards are usually older, have multiple comorbidities, e.g., liver
      cirrhosis or chronic obstructive respiratory disease, may be malnourished or
      receive peripheral or total parenteral nutrition, and frequently are undergoing
      chronic corticosteroid therapy, chemotherapy for cancer or monoclonal antibodies
      for autoimmune diseases. Such risk factors may be contemporarily present in a
      single patient increasing the risk for the development of invasive mycoses.
      Diagnosis of candidemia and invasive aspergillosis is particularly difficult in
      patients hospitalized on medical wards, since symptoms and signs have low
      specificity, and most diagnostic tests have been only validated in neutropenic
      hematologic patients, but not in those without neutropenia. Both candidemia and
      invasive aspergillosis carry significant morbidity and mortality. The aim of this
      paper is to provide a simple guide to physicians for a prompt identification and
      treatment of patients with possible or suspected invasive mycoses. 

PMID- 24871640
TI  - [Integration, chronicity and other winds of change in the "health universe":
      Tracks to advance].

PMID- 24871639
TI  - Repeatability of visual acuity testing using a psychometric function.
AB  - PURPOSE: To evaluate the repeatability of a new method of measurement of visual
      acuity by use of a psychometric function. METHODS: The visual acuity of 15
      healthy adults was measured by use of a psychometric function (PFVA) and by use
      of a conventional method using a decimal visual acuity chart (DeVA). We performed
      two tests. To evaluate intra-rater reliability, a tester measured the visual
      acuity three times for each subject, and the intraclass correlation coefficients,
      ICC (1,1), were calculated for PFVA and DeVA. Next, to evaluate inter-rater
      reliability, three testers measured the visual acuity for one subject, and the
      ICC (2,1) were calculated for PFVA and DeVA. The PFVA and DeVA of five subjects
      with ocular diseases were also measured. RESULTS: In the evaluation of intra
      rater reliability, the ICC (1,1) of the DeVA was 0.83 and the ICC (1,1) of the
      PFVA was 0.95. In the evaluation of inter-rater reliability, the ICC (2,1) of the
      DeVA was 0.88 and the ICC (2,1) of the PFVA was 0.93. In both tests the standard
      deviations of the PFVA were significantly lower than those of the DeVA. For four
      of the five subjects with ocular diseases, the PFVA was significantly improved by
      treatment. CONCLUSION: The repeatability of our method is better than that of the
      conventional method using a decimal visual acuity chart.

PMID- 24871642
TI  - Prevalence of antibody to Bordetella pertussis in neonates and prevalence of
      recent pertussis infection in pregnant women in Catalonia (Spain) in 2003 and
      2013.
AB  - BACKGROUND: Infections because of Bordetella pertussis still occur in infants and
      adults in European countries, despite vaccination coverage against pertussis
      being high. METHODS: IgG antibody titers to pertussis toxin (anti-PT) were
      assessed using an enzyme-linked immunosorbent assay test (Serion ELISA classic)
      in 353 cord blood samples from neonates of a representative sample of pregnant
      women obtained in Catalonia (Spain) in 2013. Neonates with anti-PT titers <= 40
      international units (IU)/mL were considered to be unprotected against pertussis.
      IgG-PT titers >100 IU/mL in umbilical cord samples were considered to be
      indicative of a current or recent pertussis infection (12 months) in pregnant
      women. The age-standardized prevalence of recent pertussis infection obtained in
      this study was compared with the prevalence obtained in 2003. RESULTS: The mean
      anti-PT titer in neonates was 10.8 IU/mL and 89.8% of neonates were unprotected
      against pertussis. The prevalence of unprotected neonates as defined by cord
      blood anti-PT <= 40 IU/mL was 90%. The prevalence of recent pertussis infection
      in pregnant women as defined by cord blood anti-PT >100 IU/mL was 2%. The
      diphtheria-tetanus-pertussis vaccination coverage during childhood in pregnant
      women was 75%. The age-standardized prevalence of recent pertussis infection in
      pregnant women observed in this study (2.2%) was slightly higher than the
      prevalence obtained in 2003 (1.5%), with an odds ratio = 1.45 (95% confidence
      intervals: 0.5-3.9), although differences were not statistically significant.
      CONCLUSIONS: Most neonates are unprotected against pertussis and pertussis
      infections are frequent in pregnant women in Catalonia. Infants and pregnant
      women should be the priority population groups for pertussis prevention programs
      in Catalonia.

PMID- 24871643
TI  - Inactivation of avian influenza virus, newcastle disease virus and goose
      parvovirus using solution of nano-sized scallop shell powder.
AB  - Scallop shell powder produced by calcination process - the average diameter of
      the powder particles being 20 um (SSP) - was further ground into nano-sized
      particles, with average diameter of 500 nm, here designated CaO-Nano. Solution of
      CaO-Nano could inactivate avian influenza virus within 5 sec, whereas the
      solution of SSP could not even after 1 hr incubation. CaO-Nano solution could
      also inactivate Newcastle disease virus and goose parvovirus within 5 sec and 30
      sec, respectively. The virus-inactivating capacity (neutralizing index: NI>3) of
      the solution was not reduced by the presence of 20% fetal bovine serum. CaO-Nano
      solution seems to be a good candidate of materials for enhancement of biosecurity
      in farms. 

PMID- 24871644
TI  - Development of a loop-mediated isothermal amplification method for detecting
      Streptococcus equi subsp. zooepidemicus and analysis of its use with three simple
      methods of extracting DNA from equine respiratory tract specimens.
AB  - Streptococcus equi subsp. zooepidemicus (S. zooepidemicus) is a dominant
      pathogenic bacterium in equine pneumonia. We developed a specific loop-mediated
      isothermal amplification (LAMP) method, which targets the gene encoding sorbitol
      6-phosphate 2-dehydrogenase (sorD), for detecting S. zooepidemicus and examined
      the clinical efficacies of its use in combination with each of 3 DNA extraction
      methods easily used by veterinary practitioners, namely the Loopamp PURE DNA
      Extraction Kit, InstaGene Matrix and a conventional boiling method. The LAMP
      method plus the Loopamp PURE DNA Extraction Kit gave higher rates of positivity
      than the other combinations in both clinical and spiked samples containing
      clinically significant concentrations (>1 * 10(4) CFU/ml) of S. zooepidemicus. 

PMID- 24871641
TI  - Congenital cytomegalovirus-related hospitalizations in infants <1 year of age,
      United States, 1997-2009.
AB  - BACKGROUND: An estimated 3600 infants born with congenital cytomegalovirus (cCMV)
      infection annually in the United States are symptomatic at birth. The proportion
      of infants with symptomatic cCMV infection who require hospitalization is unknown
      yet important for understanding the full disease and economic burdens of cCMV.
      METHODS: Data from the Healthcare Cost and Utilization Project Kids' Inpatient
      Databases were analyzed to determine numbers and rates of cCMV-related
      hospitalizations among infants for 1997, 2000, 2003, 2006 and 2009, the years the
      survey was conducted. A cCMV-related hospitalization was defined as a
      hospitalization with an International Classification of Diseases, 9th revision,
      Clinical Modification code of 771.1 in an infant without HIV or transplant
      related codes. After applying hospital type-specific cost-to-charge ratios and
      adjusting to 2012 US dollars, total medical costs associated with cCMV-related
      hospitalizations were assessed. Results were extrapolated to represent national
      estimates. RESULTS: Among infants <1 year of age in the United States, an
      estimated annual average of 747 cCMV-related hospitalizations (18.6/100,000 per
      year) were coded during the 5 study years; 408 (55%) were among infants <1 month
      of age (122.0/100,000 per year). Approximately 4% of hospitalizations among
      infants <1 year resulted in death. Total estimated annual cost associated with
      cCMV-related hospitalizations among the US infants <1 year was at least $14.3
      million. CONCLUSIONS: cCMV infection is associated with substantial numbers of
      hospitalizations, medical costs and mortality among the US infants. The true
      burden and costs of cCMV disease are likely much higher than our estimates when
      underascertainment of cCMV and total costs related to services and
      hospitalizations beyond the first year of life are considered.

PMID- 24871646
TI  - Diaschisis: past, present, future.
AB  - After a century of false hopes, recent studies have placed the concept of
      diaschisis at the centre of the understanding of brain function. Originally, the
      term 'diaschisis' was coined by von Monakow in 1914 to describe the
      neurophysiological changes that occur distant to a focal brain lesion. In the
      following decades, this concept triggered widespread clinical interest in an
      attempt to describe symptoms and signs that the lesion could not fully explain.
      However, the first imaging studies, in the late 1970s, only partially confirmed
      the clinical significance of diaschisis. Focal cortical areas of diaschisis (i.e.
      focal diaschisis) contributed to the clinical deficits after subcortical but only
      rarely after cortical lesions. For this reason, the concept of diaschisis
      progressively disappeared from the mainstream of research in clinical
      neurosciences. Recent evidence has unexpectedly revitalized the notion. The
      development of new imaging techniques allows a better understanding of the
      complexity of brain organization. It is now possible to reliably investigate a
      new type of diaschisis defined as the changes of structural and functional
      connectivity between brain areas distant to the lesion (i.e. connectional
      diaschisis). As opposed to focal diaschisis, connectional diaschisis, focusing on
      determined networks, seems to relate more consistently to the clinical findings.
      This is particularly true after stroke in the motor and attentional networks.
      Furthermore, normalization of remote connectivity changes in these networks
      relates to a better recovery. In the future, to investigate the clinical role of
      diaschisis, a systematic approach has to be considered. First, emerging imaging
      and electrophysiological techniques should be used to precisely map and
      selectively model brain lesions in human and animals studies. Second, the concept
      of diaschisis must be applied to determine the impact of a focal lesion on new
      representations of the complexity of brain organization. As an example, the
      evaluation of remote changes in the structure of the connectome has so far mainly
      been tested by modelization of focal brain lesions. These changes could now be
      assessed in patients suffering from focal brain lesions (i.e. connectomal
      diaschisis). Finally, and of major significance, focal and non-focal
      neurophysiological changes distant to the lesion should be the target of
      therapeutic strategies. Neuromodulation using transcranial magnetic stimulation
      is one of the most promising techniques. It is when this last step will be
      successful that the concept of diaschisis will gain all the clinical
      respectability that could not be obtained in decades of research. 

PMID- 24871647
TI  - Closing the controversies gap in prostate cancer?

PMID- 24871645
TI  - Increased globulin and its association with hemorrhagic transformation in
      patients receiving intra-arterial thrombolysis therapy.
AB  - Previous studies have identified a diverse set of predisposing factors for the
      occurrence of hemorrhagic transformation (HT), but the independent clinical
      predictors of HT after intraarterial thrombolysis have not been determined. In
      this retrospective study, we investigated the characteristics of patients with or
      without HT who had received intra-arterial thrombolysis therapy, using
      biochemical analysis, renal function test, routine blood test, blood lipid test,
      coagulation blood test, liver function test, random blood glucose test, time
      window for intra-arterial thrombolysis, recanalization, National Institutes of
      Health Stroke Scale (NIHSS) score and systolic blood pressure before intra
      arterial thrombolysis. The mortality rates were similar in the HT and non-HT
      groups (P = 0.944). In the single-factor analysis, patients with a higher
      globulin level (P <0.002), prothrombin time activity percentage (PTA; P = 0.026),
      and NIHSS score (P = 0.002), had a significantly increased risk of developing HT.
      In the multifactor logistic regression model involving globulin level, PTA, white
      blood cell count, and NIHSS score, the globulin level (P <0.001; OR, 1.185; 95%
      confidence interval [CI], 1.090-1.288), PTA (P = 0.018; OR, 1.016; 95% CI, 1.003
      1.029), white blood cell count (P = 0.025; OR, 1.097; 95% CI, 1.012-1.190) and
      NIHSS score (P = 0.003; OR, 1.097; 95% CI, 1.031-1.166) were significantly
      increased in the HT group. The increase in globulin level is an independent risk
      factor for HT in patients receiving intra-arterial thrombolysis. The possible
      mechanisms may involve inflammatory cytokines, matrix metalloproteinase 9, and
      positive acute-phase reactants synthesized by the liver.

PMID- 24871648
TI  - A systematic review on natural medicines for the prevention and treatment of
      Alzheimer's disease with meta-analyses of intervention effect of ginkgo.
AB  - We performed a systematic review to evaluate the efficacy of natural medicines
      for the treatment of Alzheimer's disease (AD) in randomized controlled trials
      (RCTs). Disease-specific and intervention terms were searched in MEDLINE, EMBASE,
      the Cochrane Library and PsycINFO to identify RCTs for the AD intervention of
      natural medicines, and searched for literatures in English language. The RCTs
      compared natural medicines and either placebo or orthodox medication in AD
      patients. The quality of literature was evaluated by Jadad's score and the
      Cochrane assessing tool to reduce the risk of bias. Meta-analysis and the
      heterogeneity of results across the trials were performed. Out of the
      literatures, 21 clinical reports were included in this review that satisfied the
      particular selection criteria. Apart from Ginkgo, other treatments we came across
      had minimal benefits and/or the methodological quality of the available trials
      was poor. The meta-analyses showed that Ginkgo had better outcomes than the
      placebo, with the standardized mean difference (SMD) between Ginkgo and the
      placebo on cognition being -1.62 (95% CI: -2.69 to -0.56) and on activities of
      daily living being -1.55 (95% CI: -2.55 to -0.55), with the existence of
      significant heterogeneity across studies. The meta-analysis for assessing the
      prevention effect of Ginkgo against AD suggested that risk ratio (RR) is 1.06
      (95% CI: 0.92 to 1.22) between Gingko and the placebo, with no significant
      heterogeneity across studies (test for heterogeneity, p = 0.49). Our results
      suggest that Ginkgo may help established AD patients with cognitive symptoms but
      cannot prevent the neurodegenerative progression of the disease. 

PMID- 24871649
TI  - Platycladus orientalis leaves: a systemic review on botany, phytochemistry and
      pharmacology.
AB  - Platycladus orientalis leaves (Cebaiye) have been used for thousands of years as
      traditional Chinese medicine (TCM). According to the theory of TCM, they are
      categorized as a blood-cooling and hematostatic herb. In clinical practice, they
      were usually prescribed with heat-clearing herbs to reinforce the efficacy of
      hemostasis. The review provides the up-to-date information from 1980 to present
      that is available on the botany, processing research, phytochemistry,
      pharmacology and toxicology of the leaves. The information is collected from
      scientific journals, books, theses and reports via library and electronic search
      (Google Scholar, Pubmed and CNKI). Through literature reports, we can find that
      the leaves show a wide spectrum of pharmacological activities, such as anti
      inflammatory, antioxidant, antimicrobial, disinsection, anticancer, diuretic,
      hair growth-promoting, neuroprotective and antifibrotic activities. Diterpene and
      flavonoids would be active constituents in P. orientalis leaves. Many studies
      have provided evidence for various traditional uses. However, there is a great
      need for additional studies to elucidate the mechanism of blood-cooling and
      hematostatic activity of the leaves. Therefore, the present review on the botany,
      traditional uses, phytochemistry and toxicity has provided preliminary
      information for further studies of this herb. 

PMID- 24871651
TI  - Effect of cantharidins in chemotherapy for hepatoma: a retrospective cohort
      study.
AB  - This study aimed to evaluate the effects of cantharidins, a traditional Chinese
      medicine, in chemotherapy for the treatment of hepatoma. From August 2011 to
      December 2012, 96 patients with hepatoma, who were eligible for transcatheter
      hepatic arterial chemoembolization and received cantharidins, were selected for
      comparison with the control group of 95 patients without cantharidins. The
      treatment effect, clinical symptoms and adverse effects were analyzed. The
      results of the study showed that the cantharidins group had a higher overall
      efficient rate than the control group (p < 0.001). The improvement rate of the
      Karnofsky score in the cantharidins group was significantly higher than that of
      the control group (p = 0.014). In the cantharidins group, there was a decrease in
      white blood cell (WBC) count and gastrointestinal response rates were lower than
      those of the control group (p < 0.05). Therefore, the traditional Chinese
      medicine cantharidins showed effects of easing the progress of liver cancer,
      relieving side effects of chemotherapy and improving the quality of life in the
      treatment of hepatoma. 

PMID- 24871650
TI  - Traditional Chinese medicine: a treasured natural resource of anticancer drug
      research and development.
AB  - To discover and develop novel natural compounds, active ingredients, single herbs
      and combination formulas or prescriptions in traditional Chinese medicine (TCM)
      with therapeutic selectivity that can preferentially kill cancer cells and
      inhibit the amplification of cancer without significant toxicity is an important
      area in cancer therapy. A lot of valuable TCMs were applied as alternative or
      complementary medicines in the United States and Europe. But these TCMs, as one
      of the main natural resources, were widely used to research and develop new drugs
      in Asia. In TCMs, some specific herbs, animals, minerals and combination formulas
      were recorded and exploited due to their active ingredients and specific natural
      compounds with antitumor activities. The article focused on the antitumor
      properties of natural compounds and combination formulas or prescriptions in
      TCMs, described its influence on tumor progression, angiogenesis, metastasis, and
      revealed its mechanisms of antitumor and inhibitory action. Among the nature
      compounds, triptolide, berberine, matrine, oxymatrine, kurarinone and
      deoxypodophyllotoxin (DPT) with specific molecular structures have been
      separated, purified, and evaluated their antitumor properties in vitro and in
      vivo. Cancer is a multifactorial and multistep disease, so the treatment effect
      of combination formulas and prescriptions in TCMs involving multi-targets and
      multi-signal pathways on tumor may be superior than that of agents targeting a
      single molecular target alone. Shi Quan Da Bu Tang and Yanshu injection, as well
      known combination formulas and prescriptions in TCMs, have shown an excellent
      therapeutic effect on cancer. 

PMID- 24871652
TI  - Clinical efficacy of acupuncture as an adjunct to methadone treatment services
      for heroin addicts: a randomized controlled trial.
AB  - Scant scientific evidence supports the efficacy of acupuncture in the treatment
      of opiate dependence. The purpose of this study was to examine the effectiveness
      of acupuncture for heroin addicts on methadone maintenance by measuring the daily
      consumption of methadone, variations in the 36-item Short Form Health Survey-36
      (SF-36) and Pittsburgh Sleep Quality Index (PSQI) scores, and heroin craving.
      Sixty heroin addicts were randomly assigned to true acupuncture
      (electroacupuncture at the Hegu [LI4] and Zusanli [ST36] acupoints, as well as
      acupuncture at the Ear Shenmen) or sham acupuncture (minimal acupuncture at the
      Hegu and Zusanli acupoints without electrical stimulation and superficial
      acupuncture at the Ear Shenmen), twice weekly for 4 weeks. From week 2 onwards,
      the daily dose of methadone was reduced by a significantly greater amount with
      true acupuncture compared with sham acupuncture. True acupuncture was also
      associated with a greater improvement in sleep latency at follow-up. All adverse
      events were mild in severity. Acupuncture appears to be a useful adjunct to
      methadone maintenance therapy (MMT) in heroin addiction. 

PMID- 24871653
TI  - Indispensable value of clinical trials in the modernization of traditional
      Chinese medicine: 12 years' experience at CUHK and future perspectives.
AB  - The last decade has seen a wealth of information reporting the beneficial effects
      of Chinese herbal medicines. While a lot more studies were done using in vitro
      and in vivo research platforms, much fewer investigations were conducted
      according to evidence-based requirements in clinical settings. The Institute of
      Chinese Medicine at the Chinese University of Hong Kong (CUHK) has had the
      opportunity to collaborate with clinicians over the years to initiate and conduct
      dozens of clinical trials investigating and verifying the therapeutic values of
      Chinese herbs in selected disease conditions. Of the many disorders, we chose to
      focus on those that are known for their difficulties achieving perfect results
      with conventional treatment methods. Examples include non-healing ulcers,
      allergic conditions, degenerative diseases and cancer. Protective effects of the
      herbs in such chronic diseases as coronary artery disease and osteoporosis were
      also part of our focus. Even in healthy individuals and those recovering from
      chemotherapy, Chinese herbs could help with the immune system and were studied in
      our clinical trials as well. This paper aims to highlight the important findings
      from these clinical studies while at the same time, stressing the indispensable
      value of clinical trials in modernizing the use of Chinese herbs in present-day
      medicine. 

PMID- 24871654
TI  - Blood pressure lowering effect of Korea ginseng derived ginseol K-g1.
AB  - We investigated the effect of Panax ginseng extract, which is rich in the
      ginsenoside protopanaxatriol (Ginseol K-g1), on blood pressure (BP). Adults over
      20 years old with a systolic BP (SBP) between 120 and 159 mm Hg or a diastolic BP
      (DBP) between 80 and 99 mm Hg were included. At the end of an initial 2-week
      washout period, the patients were divided into three groups: the control group
      (placebo), the low-dose Ginseol K-g1 group (100 mg), and the high-dose Ginseol K
      g1 (300 mg) group. The primary end point was the difference in seated SBP (seSBP)
      and seated DBP (seDBP) changes between the placebo and Ginseol K-g1 groups after
      8 weeks of treatment. A total of 90 subjects participated in the study (mean age;
      55.2 +/- 11.8 years, 43 males). At week 8, levels of seSBP and seDBP were
      significantly decreased from baseline in the high-dose Ginseol K-g1 group (-3.1
      mm Hg and -2.3 mm Hg, respectively, p < 0.05). In contrast, there was no
      significant decrease in seSBP or seDBP in the control or low-dose Ginseol K-g1
      groups. No significant difference of seSBP and seDBP was identified among the
      three treatment groups at week 8. In patients who had a seSBP >= 130 mm Hg or an
      seDBP >= 85 mm Hg, the high dose of Ginseol K-g1 decreased the BP compared with
      the control group at week 4; however, there was no significant difference at week
      8. The proportions of patients who experienced adverse events were comparable
      among the treatment groups. In conclusion, Ginseol K-g1 has a favorable effect on
      BP after 4 weeks of treatment, especially at a high dose. However, the effect is
      not maintained over 8 weeks. (Clinical trial registration information is
      available at http://www.clinicaltrials.gov , identifier: NCT01483430.). 

PMID- 24871655
TI  - Magnolol reduced TNF-alpha-induced vascular cell adhesion molecule-1 expression
      in endothelial cells via JNK/p38 and NF-kappaB signaling pathways.
AB  - Expression of cell adhesion molecules by the endothelium and the attachment of
      leukocytes to these cells play major roles in inflammation and cardiovascular
      disorders. Magnolol, a major active component of Magnolia officinalis, has
      antioxidative and anti-inflammatory properties. In the present study, the effects
      of magnolol on the expression of vascular cell adhesion molecule-1 (VCAM-1) in
      human aortic endothelial cells (HAECs) and the related mechanisms were
      investigated. TNF-alpha induced VCAM-1 protein expression and mRNA stability were
      significantly decreased in HAECs pre-treated with magnolol. Magnolol
      significantly reduced the phosphorylation of ERK, JNK, and p38 in TNF-alpha
      treated HAECs. The decrease in VCAM-1 expression in response to TNF-alpha
      treatment was affected by JNK and p38 inhibitors, not by an ERK inhibitor.
      Magnolol also attenuates NF-kappaB activation and the translocation of HuR (an
      RNA binding protein) in TNF-alpha-stimulated HAECs. The VCAM-1 expression was
      weaker in the aortas of TNF-alpha-treated apo-E deficient mice with magnolol
      treatment. These data demonstrate that magnolol inhibits TNF-alpha-induced
      JNK/p38 phosphorylation, HuR translocation, NF-kappaB activation, and thereby
      suppresses VCAM-1 expression resulting in reduced leukocyte adhesion. Taken
      together, these results suggest that magnolol has an anti-inflammatory property
      and may play an important role in the prevention of atherosclerosis and
      inflammatory responses. 

PMID- 24871656
TI  - Ixeris dentata decreases ER stress and hepatic lipid accumulation through
      regulation of ApoB secretion.
AB  - Nonalcoholic fatty liver disease (NAFLD) is caused by the hepatic accumulation of
      saturated fatty acids involving the ER stress mechanism. Secretion of apo lipid
      carrier proteins and their binding to hepatic TG and cholesterol are affected by
      ER stress. This study was designed to identify ER stress regulators with
      potential effects against hepatic lipid accumulation. Ixeris dentata (IXD) is a
      traditional herbal remedy for indigestion, hepatitis, and diabetes used in Korea,
      Japan, and China. To examine the regulatory effects of IXD against hepatic lipid
      accumulation and elucidate its suggested mechanism of ER stress, HepG2
      hepatocytes were treated with IXD extract in the presence of palmitate. While
      palmitate induced an ER stress response in hepatocytes, as indicated by the
      upregulation of PERK, increased eukaryotic initiation factor 2alpha (eIF2alpha)
      phosphorylation, enhanced expression of GADD153/C/EBP homologous protein (CHOP),
      and reduced secretion of apoB resulting in hepatic cellular accumulation of
      triglycerides (TG) and cholesterol, IXD extract significantly inhibited the lipid
      accumulation and PERK/eIF2alpha/CHOP-axis of the ER stress response. The
      inhibition of the PERK/eIF2alpha/CHOP signaling pathway by IXD in palmitate
      treated cells suggests that IXD regulates hepatic dyslipidemia through the
      regulation of ER stress. 

PMID- 24871658
TI  - Effects of Psoraleae fructus and its major component psoralen on Th2 response in
      allergic asthma.
AB  - This study is aimed to evaluate the effects of Psoraleae fructus (PF) on Th2
      responses in a rat model of asthma in vivo and psoralen, a major constituent in
      PF, on Th2 responses in vitro. A rat model of asthma was established by
      sensitization and challenged with ovalbumin (OVA). Airway hyperresponsiveness was
      detected by direct airway resistance analysis. Lung tissues were examined for
      cell infiltration and mucus hypersecretion. Bronchoalveolar lavage fluid (BALF)
      was assessed for cytokine levels. In vitro study, Th2 cytokine production was
      evaluated in the culture supernatant of D10.G4.1 (D10 cells) followed by the
      determination of cell viability, meanwhile Th2 transcription factor GATA-3
      expression in D10 cells was also determined. The oral administration of PF
      significantly reduced airway hyperresponsiveness (AHR) to aerosolized
      methacholine and decreased IL-4 and IL-13 levels in the BALF. Histological
      studies showed that PF markedly inhibited inflammatory infiltration and mucus
      secretion in the lung tissues. In vitro study, psoralen significantly suppressed
      Th2 cytokines of IL-4, IL-5 and IL-13 by ConA-stimulated D10 cells without
      inhibitory effect on cell viability. Furthermore, GATA-3 protein expression was
      also markedly reduced by psoralen. This study demonstrated that PF exhibited
      inhibitory effects on hyperresponsiveness and airway inflammation in a rat model
      of asthma, which was associated with the suppression of Th2 response. Psoralen, a
      major constituent of PF, has immunomodulatory properties on Th2 response in
      vitro, which indicated that psoralen might be a critical component of PF for its
      therapeutic effects. 

PMID- 24871657
TI  - Houttuynia cordata attenuates lipid accumulation via activation of AMP-activated
      protein kinase signaling pathway in HepG2 cells.
AB  - Houttuynia cordata (H. cordata) from the family Saururaceae is a perennial herb
      native to Southeast Asia. It possesses a range of medicinal properties to treat
      several disease symptoms including allergic inflammation and anaphylaxis. In the
      present investigation, we provided the molecular mechanisms underlying the role
      of H. cordata extract (HCE) in the prevention of high glucose-induced lipid
      accumulation in human HepG2 hepatocytes. HepG2 cells were pre-treated with
      various concentrations of HCE (0, 10, 20, 40, and 80 MUg/mL) and treated with
      serum-free medium with normal glucose (5 mM) for 1 h, followed by exposure to
      high glucose (25 mM D-glucose) for 24 h. HCE significantly and dose-dependently
      attenuated lipid accumulation in human HepG2 hepatocytes when exposed to high
      glucose (25 mM D-glucose) (p < 0.05, p < 0.01 and p < 0.001 at 20, 40, and 80
      MUg/mL concentrations, respectively). Further, HCE attenuated the expression of
      fatty acid synthase (FAS), sterol regulatory element-binding protein-1 and
      glycerol 3-phosphate acyltransferases (GPATs). The adenosine monophosphate
      activated protein kinase (AMPK) was also activated by HCE treatment when exposed
      to high glucose (25 mM D-glucose) in human HepG2 hepatocytes. This study suggests
      the hypolipidemic effects of HCE by the inhibition of lipid biosynthesis mediated
      through AMPK signaling, which may play an active role and can be developed as an
      anti-obesity agent. 

PMID- 24871659
TI  - Effects of cichoric acid extract from Echinacea purpurea on collagen-induced
      arthritis in rats.
AB  - Cichoric acid extract (CAE) from Echinacea purpurea L. was used to investigate
      the anti-arthritic effect by using collagen-induced arthritis (CIA) rat model.
      The hind paw swelling volume and the body weight were measured and recorded. All
      the drug solutions were administered orally to rats for a total of 28 days. On
      day 28, the rats were anaesthetized and decapitated. The thymus and spleen were
      weighed for the determination of the organ index. The concentration of tumor
      necrosis factor alpha (TNFalpha), interleukin-1 beta (IL-1beta) and prostaglandin
      E2 (PGE-2) in the serum was measured using commercially available ELISA kits.
      Total and phosphor-NF-kappaB and Cox-2 protein expression in synovial tissues
      were determined by histological slides quantification and western blot analysis.
      Our data showed that administration of all doses of CAE (8, 16, and 32 mg/kg)
      significantly decreased the paw swelling, restored body weight gain and decreased
      the organ index of the thymus and spleen compared with that of the CIA group. CAE
      (8, 16, and 32 mg/kg) treatment significantly reduced the levels of TNFalpha, IL
      1beta and PGE-2 in serum compared with the CIA group. Histopathological analysis
      demonstrated that CAE has obvious anti-arthritic activity. In addition, CAE (32
      mg/kg) significantly decreased the levels of nuclear factor-kappaB (NF-kappaB),
      TNFalpha and cyclooxygenase 2 (Cox-2) in synovium tissues of the ankle joint
      compared with the CIA group. Furthermore, CAE administration significantly
      decreased the protein expression of phosphor-NF-kappaB and Cox-2 in synovium
      tissues of the knee joint compared with the CIA group. The results suggest that
      the anti-inflammatory activity of CAE may account for its anti-arthritic effect,
      and CAE could be a potential therapeutic drug for the treatment of rheumatoid
      arthritis (RA). 

PMID- 24871660
TI  - S-allyl L-cysteine protects the retina against kainate excitotoxicity in the rat.
AB  - Excitotoxicity has been proposed to play a pivotal role in retinal ischemia.
      Retinal ischemia-associated ocular disorders are vision threatening. The aim was
      to also examine whether and how S-allyl L-cysteine (SAC) can protect the retina
      against kainate excitotoxicity. In vivo retinal excitotoxicity was induced by an
      intravitreous injection of 100 MUM kainate into a Wistar rat eye for 1 day. The
      management and mechanisms involved in the processes were evaluated by
      electrophysiology, immunohistochemistry, histopathology, and various biochemical
      approaches. In the present study, the cultured retinal cells were shown to
      possess kainate receptors. The defined retinal excitotoxic changes were
      characterized by a decrease in electroretinogram (ERG) b-wave amplitudes, a loss
      of the fluorogold retrograde labeled retinal ganglion cells (RGCs), an increase
      in the apoptotic cells in the RGC layer, and an increase in vimentin or glial
      fibrillary acidic protein (GFAP) immunoreactivity, a marker for Muller cells. An
      up-regulation in the mRNA levels of inducible nitric oxide synthase (iNOS) and
      matrix metalloproteinases-9 (MMPs-9) was also detected in the retina subjected to
      kainate excitoxicity. Importantly, the excitotoxicity-induced alterations were
      significantly blunted when 100 MUM SAC and/or the kainate receptor antagonist
      CNQX was applied. Conclusively, SAC would seem to protect the retina against
      kainate excitotoxicity via an inhibition of the up-regulation of iNOS and MMP-9
      as well as a modulation of glial activation and apoptosis. 

PMID- 24871661
TI  - Effects of baicalin against UVA-induced photoaging in skin fibroblasts.
AB  - Ultraviolet A (UVA) radiation contributes to skin photoaging. Baicalin, a plant
      derived flavonoid, effectively absorbs UV rays and has been shown to have anti
      oxidant and anti-inflammatory properties that may delay the photoaging process.
      In the current study, cultured human skin fibroblasts were incubated with 50
      MUg/ml baicalin 24 hours prior to 10 J/cm(2) UVA irradiation. In order to examine
      the efficacy of baicalin treatment in delaying UVA-induced photoaging, we
      investigated aging-related markers, cell cycle changes, anti-oxidant activity,
      telomere length, and DNA damage markers. UVA radiation caused an increased
      proportion of beta-Gal positive cells and reduced telomere length in human skin
      fibroblasts. In addition, UVA radiation inhibited TGF-beta1 secretion, induced G1
      phase arrest, reduced SOD and GSH-Px levels, increased MDA levels, enhanced the
      expression of MMP-1, TIMP-1, p66, p53, and p16 mRNA, reduced c-myc mRNA
      expression, elevated p53 and p16 protein expression, and reduced c-myc protein
      expression. Baicalin treatment effectively protected human fibroblasts from these
      UVA radiation-induced aging responses, suggesting that the underlying mechanism
      involves the inhibition of oxidative damage and regulation of the expression of
      senescence-related genes, including those encoding for p53, p66(Shc) and p16. 

PMID- 24871662
TI  - Bufalin induces cell death in human lung cancer cells through disruption of DNA
      damage response pathways.
AB  - Bufalin is a key component of a Chinese medicine (Chan Su) and has been proved
      effective in killing various cancer cells. Its role in inducing DNA damage and
      the inhibition of the DNA damage response (DDR) has been reported, but none have
      studied such action in lung cancer in detail. In this study, we demonstrated
      bufalin-induced DNA damage and condensation in NCI-H460 cells through a comet
      assay and DAPI staining, respectively. Western blotting indicated that bufalin
      suppressed the protein levels associated with DNA damage and repair, such as a
      DNA dependent serine/threonine protein kinase (DNA-PK), DNA repair proteins
      breast cancer 1, early onset (BRCA1), 14-3-3 sigma (an important checkpoint
      keeper of DDR), mediator of DNA damage checkpoint 1 (MDC1), O6-methylguanine-DNA
      methyltransferase (MGMT) and p53 (tumor suppressor protein). Bufalin could
      activate phosphorylated p53 in NCI-H460 cells. DNA damage in NCI-H460 cells after
      treatment with bufalin up-regulated its ATM and ATR genes, which encode proteins
      functioning as sensors in DDR, and also up-regulated the gene expression (mRNA)
      of BRCA1 and DNA-PK. But bufalin suppressed the gene expression (mRNA) of p53 and
      14-3-3 sigma, however, bufalin did not significantly affect the mRNA of MGMT. In
      conclusion, bufalin induced DNA damage in NCI-H460 cells and also inhibited its
      DNA repair and checkpoint function. 

PMID- 24871664
TI  - Starch nanocrystal stabilized Pickering emulsion polymerization for
      nanocomposites with improved performance.
AB  - Latex/starch nanocrystal (SNC) nanocomposite dispersions were successfully
      synthesized via a one-step surfactant-free Pickering emulsion polymerization
      route using SNC as the sole stabilizer. The effect of the SNC content, initiator
      type and comonomer on the particle size, colloidal stability, and film properties
      were investigated. Both HCl and H2SO4-hydrolysed starch nanocrystals, each
      bearing different surface charges, were used as Pickering emulsion stabilizing
      nanoparticles. SNCs from HCl hydrolysis were found to provide a better
      stabilization effect, giving rise to a polymer dispersion with a lower average
      particle size. The mechanistic aspects of the Pickering emulsion polymerization
      were also discussed. Nanocomposites formed by film-casting the polymer Pickering
      emulsions showed better mechanical properties and optical transparency than those
      obtained by blending the polymer emulsion with a nanocrystal dispersion, showing
      the one-pot route to nanocomposite precursors to be doubly advantageous.
      Therefore, this in situ polymerization technique not only facilitates the use of
      SNC nanoparticles, it also provides a valuable nanocomposite with enhanced
      mechanical properties and high transparency level. 

PMID- 24871663
TI  - Novel target genes responsive to apoptotic activity by Ocimum gratissimum in
      human osteosarcoma cells.
AB  - Osteosarcoma (OS) is a type of bone cancer. Eighty percent of this tumor will
      metastasize to the lungs or liver, and as a result, patients generally need
      chemotherapy to improve survival possibility. Recently, antitumor activity has
      been reported in Ocimum gratissimum aqueous extract (OGE), which has been the
      focus of recent extensive studies on therapeutic strategies due to its
      antioxidant properties. We performed pharmacogenomics analyses for the effect of
      OGE on human osteosarcoma U2-OS and HOS cell growth. Cell viability, Western blot
      and flow cytometry analysis were performed before performing pharmacogenomics
      analyses for the effect of OGE on human osteosarcoma U2-OS and HOS cell growth,
      including cDNA microarray and RT-PCR assays. Cell viability assays revealed that
      OGE significantly and dose-dependently decreased the viability of U2-OS and HOS
      cells. Increases in cell shrinkage, Sub-G1 fragments and the activation of
      caspase 3 indicated that OGE induced cell apoptosis in U2-OS and HOS cells. There
      was no change in human osteoblast hFOS cells. cDNA microarray assay demonstrated
      that the expression of cell cycle regulators, apoptosis-related factors and cell
      proliferation markers were all modified by OGE treatment. RT-PCR analysis also
      confirmed the down-regulation of SKA2 and BUB1B, and the up-regulation of
      PPP1R15A, SQSTM1, HSPA1B, and DDIT4 by OGE treatment. The finding of anticancer
      activity in OGE and the identification of some potential target genes raise the
      expectation that OGE may become a useful therapeutic drug for human OS. 

PMID- 24871665
TI  - Connecting optimism to our gastrointestinal passion.

PMID- 24871667
TI  - Everyday life, healthcare, and self-care management among people with irritable
      bowel syndrome: an integrative review of qualitative research.
AB  - Irritable bowel syndrome is a commonly recognized chronic disease in all
      healthcare settings. This integrative review investigated current knowledge about
      adults' illness-related experiences of this disease from the perspectives of
      everyday life, healthcare, and self-care management. The overarching findings
      related to everyday life with irritable bowel syndrome were life-limiting
      experiences of the body-self as unfamiliar and of the body and symptoms as
      shameful and unpredictable. The limitations manifested as lack of ability to move
      about freely, fulfill ambitions or commitments at work, maintain social
      activities, uphold or develop close and/or sexual relationships and parenting,
      and live a life with spontaneity. Physical condition, knowledge about
      disease/illness-related matters, and one's own perceived ability to find adequate
      strategies were significant for the ability of self-care management. Healthcare
      was experienced as being unsupportive and not providing information and guidance
      for enabling self-care management. These results suggest a need for controlled
      intervention trials of healthcare models that take as their point of departure
      the individual's experience of illness, needs, and life situation, and that
      enable learning and sharing of illness experiences, combined with the provision
      of scientific knowledge and advice from healthcare professionals.

PMID- 24871666
TI  - A high-fiber diet may improve bowel function and health-related quality of life
      in patients with Crohn disease.
AB  - Crohn disease is a chronic disorder characterized by episodes of epithelial
      inflammation in the gastrointestinal tract for which there is no cure. The
      prevalence of Crohn disease increased in civilized nations during the time period
      in which food sources were industrialized in those nations. A characteristic of
      industrialized diets is the conspicuous absence of cereal fiber. The purpose of
      this 2-group, randomized, controlled study was to investigate the effects of
      fiber-related dietary instructions specifying wheat bran consumption on health
      related quality of life and gastrointestinal function in individuals diagnosed
      with Crohn disease, as measured by the Inflammatory Bowel Disease Questionnaire
      and the partial Harvey Bradshaw Index, respectively. Results demonstrated that
      consuming a wheat bran-inclusive diet was feasible and caused no adverse effects,
      and participants consuming whole wheat bran in the diet reported improved health
      related quality of life (p = .028) and gastrointestinal function (p = .008)
      compared to the attention control group. The results of a secondary aim, to
      investigate differences in measures of systemic inflammation, found no group
      differences in C-reactive protein or erythrocyte sedimentation rates. This study
      suggests that diet modification may be a welcomed complementary therapy for
      individuals suffering gastrointestinal disruption associated with Crohn disease.

PMID- 24871668
TI  - Fast-track recovery after major liver and pancreatic resection from the nursing
      point of view.
AB  - Postoperative fast-track recovery protocols combine various methods to support
      immediate care of patients who undergo major surgery. These protocols include
      control of postoperative pain and early beginning of oral diet and mobilization.
      The combination of these approaches may reduce the rate of postoperative
      complications and facilitate hospital discharge. The aim of this study was to
      evaluate progress and parameters of fast-track recovery after major liver and
      pancreatic resection. A descriptive bibliographical review from 2001 to 2012 via
      electronic databases such as MEDLINE, PubMed, and Google Scholar was undertaken.
      Articles that focused on a fast-track protocol were studied. Reports focusing on
      the implementation of a fast-track protocol in the postoperative recovery of
      patients after major hepatectomy or pancreatectomy were selected. Fast-track
      protocols may be applicable to patients recovering after major liver or
      pancreatic resection. Future research should be focused on particular parameters
      of the fast-track protocol separately.

PMID- 24871670
TI  - A rare cause of gastrointestinal bleeding in a young female: jejunal
      gastrointestinal stromal tumor.

PMID- 24871669
TI  - Outpatient interventions for hepatology patients with fluid retention: a review
      and synthesis of the literature.
AB  - Cirrhosis of the liver was the 12th leading cause of death in the United States,
      according to the 2010 Vital Statistics Report. Cirrhosis is responsible for more
      than 150,000 hospitalizations each year. Similar to heart failure, severe fluid
      retention in cirrhotic patients leads to hospitalizations and increase in
      resource utilization. Outpatient interventions can be used to decrease
      preventable hospitalizations. The existing literature was explored to determine
      what interventions can be implemented in an outpatient setting that may reduce or
      prevent hospital admissions for cirrhotic patients with fluid retention.
      Seventeen articles were included in the review of the literature. There were 9
      randomized controlled trials that yielded a total of 1,694 patients. One meta
      analysis yielded 5 randomized controlled trials with 330 patients. Three cohort
      studies yielded 86 patients. One systematic review yielded 2,115 articles and 2
      literature reviews yielded 110 articles. One report from an expert committee was
      included in the review. Findings from the studies identified 6 main interventions
      that can be used for outpatient management of cirrhotic patients with fluid
      retention and may prevent related hospitalizations. These include dietary sodium
      restriction, diuretics, daily weights, albumin infusions and paracentesis,
      placement of a transjugular intrahepatic portosystemic shunt, and telephone
      management.

PMID- 24871671
TI  - Rectal route in the 21st Century to treat children.
AB  - The rectal route can be considered a good alternative to the oral route for the
      paediatric population because these dosage forms are neither to be swallowed nor
      need to be taste-masked. Rectal forms can also be administered in an emergency to
      unconscious or vomiting children. Their manufacturing cost is low with excipients
      generally regarded as safe. Some new formulation strategies, including
      mucoadhesive gels and suppositories, were introduced to increase patient
      acceptability. Even if recent paediatric clinical studies have demonstrated the
      equivalence of the rectal route with others, in order to enable the use of this
      promising route for the treatment of children in the 21st Century, some effort
      should be focused on informing and educating parents and care givers. This review
      is the first ever to address all the aforementioned items, and to list all drugs
      used in paediatric rectal forms in literature and marketed products in developed
      countries. 

PMID- 24871672
TI  - Ribozyme-based aminoglycoside switches of gene expression engineered by genetic
      selection in S. cerevisiae.
AB  - Systems for conditional gene expression are powerful tools in basic research as
      well as in biotechnology. For future applications, it is of great importance to
      engineer orthogonal genetic switches that function reliably in diverse contexts.
      RNA-based switches have the advantage that effector molecules interact
      immediately with regulatory modules inserted into the target RNAs, getting rid of
      the need of transcription factors usually mediating genetic control. Artificial
      riboswitches are characterized by their simplicity and small size accompanied by
      a high degree of modularity. We have recently reported a series of hammerhead
      ribozyme-based artificial riboswitches that allow for post-transcriptional
      regulation of gene expression via switching mRNA, tRNA, or rRNA functions. A more
      widespread application was so far hampered by moderate switching performances and
      a limited set of effector molecules available. Here, we report the re-engineering
      of hammerhead ribozymes in order to respond efficiently to aminoglycoside
      antibiotics. We first established an in vivo selection protocol in Saccharomyces
      cerevisiae that enabled us to search large sequence spaces for optimized
      switches. We then envisioned and characterized a novel strategy of attaching the
      aptamer to the ribozyme catalytic core, increasing the design options for
      rendering the ribozyme ligand-dependent. These innovations enabled the
      development of neomycin-dependent RNA modules that switch gene expression up to
      25-fold. The presented aminoglycoside-responsive riboswitches belong to the best
      performing RNA-based genetic regulators reported so far. The developed in vivo
      selection protocol should allow for sampling of large sequence spaces for
      engineering of further optimized riboswitches. 

PMID- 24871673
TI  - Characterization of carbapenem resistance mechanisms in Klebsiella pneumoniae and
      in vitro synergy of the colistin-meropenem combination.
AB  - In this prospective study, consecutive isolates of Klebsiella pneumoniae were
      tested for different mechanisms of carbapenem resistance using the modified Hodge
      test (MHT), Rosco Neo-Sensitabs (ROSCO). Phenylalanine arginine beta
      naphthylamide assay (PABN) inhibitor-based test was done on isolates in which the
      mechanism of resistance was not identifiable by the ROSCO. Among 105 selected
      isolates, carbapenemase production was noted in 100 (95%) by MHT and ROSCO showed
      97 (92.4%) inhibition with dipicolinic acid signifying the production of MBL. PCR
      amplification was positive in 90 (86%) isolates for bla(NDM-1) and 46 (44%)
      isolates for bla(OXA-48). 54 (51%) isolates were positive for bla(CTX-M) and all
      belonged to bla(CTX-M) group 1. Isolates co produced bla(OXA-48) (31/105, 30%)
      and bla(CTX-M) (40/105, 38%) in combination with the carbapenemase (bla(NDM-1))
      gene. Five colistin-resistant isolates were positive for bla(OXA-48). Eight
      isolates did not show inhibition with any of the inhibitor containing disks and
      found to be positive for bla(OXA-48). Isolates were tested for colistin-meropenem
      synergy and detection rate was higher by the checkerboard (48%) than E-test
      method (35%). Our study necessitates continuous surveillance to recognize the
      predominant machinery of resistance in a particular geographical region to
      formulate effective control measures.

PMID- 24871674
TI  - The Conqueror Worm: recent advances with cholinergic anthelmintics and techniques
      excite research for better therapeutic drugs.
AB  - The following account is based on a review lecture given recently at the British
      Society of Parasitology. We point out that nematode parasites cause very
      widespread infections of humans, particularly in economically underdeveloped
      areas where sanitation and hygiene are not adequate. In the absence of adequate
      clean water and effective vaccines, control and prophylaxis relies on
      anthelmintic drugs. Widespread use of anthelmintics to control nematode parasites
      of animals has given rise to the development of resistance and so there is a
      concern that similar problems will occur in humans if mass drug administration is
      continued. Recent research on the cholinergic anthelmintic drugs has renewed
      enthusiasm for the further development of cholinergic anthelmintics. Here we
      illustrate the use of three parasite nematode models, Ascaris suum,
      Oesophagostomum dentatum and Brugia malayi, microfluidic techniques and the
      Xenopus oocyte expression system for testing and examining the effects of
      cholinergic anthelmintics. We also show how the combination of derquantel, the
      selective nematode cholinergic antagonist and abamectin produce increased
      inhibition of the nicotinic acetylcholine receptors on the nematode body muscle.
      We are optimistic that new compounds and combinations of compounds can limit the
      effects of drug resistance, allowing anthelmintics to be continued to be used for
      effective treatment of human and animal helminth parasites. 

PMID- 24871680
TI  - Erratum to: The nature of epistemic virtues in the practice of medicine.

PMID- 24871675
TI  - Beyond meatless, the health effects of vegan diets: findings from the Adventist
      cohorts.
AB  - Vegetarians, those who avoid meat, and vegans, additionally avoiding dairy and
      eggs, represent 5% and 2%, respectively, of the US population. The aim of this
      review is to assess the effects of vegetarian diets, particularly strict
      vegetarian diets (i.e., vegans) on health and disease outcomes. We summarized
      available evidence from three prospective cohorts of Adventists in North America:
      Adventist Mortality Study, Adventist Health Study, and Adventist Health Study-2.
      Non-vegetarian diets were compared to vegetarian dietary patterns (i.e., vegan
      and lacto-ovo-vegetarian) on selected health outcomes. Vegetarian diets confer
      protection against cardiovascular diseases, cardiometabolic risk factors, some
      cancers and total mortality. Compared to lacto-ovo-vegetarian diets, vegan diets
      seem to offer additional protection for obesity, hypertension, type-2 diabetes,
      and cardiovascular mortality. Males experience greater health benefits than
      females. Limited prospective data is available on vegetarian diets and body
      weight change. Large randomized intervention trials on the effects of vegetarian
      diet patterns on neurological and cognitive functions, obesity, diabetes, and
      other cardiovascular outcomes are warranted to make meaningful recommendations. 

PMID- 24871679
TI  - Assessment of Mean Platelet Volume in men with vasculogenic and nonvasculogenic
      erectile dysfunction.
AB  - Mean platelet (PLT) activation has an important role in the development of
      vascular diseases. In this study, we aimed to investigate the PLT volume in
      patients with vasculogenic and nonvasculogenic erectile dysfunction (ED) and
      compare it with the control group. Mean PLT volume (MPV) levels were measured in
      50 patients with vasculogenic ED, in 30 patients who developed ED after radical
      prostatectomy (nonvasculogenic) and in 40 healthy controls. Ages were similar
      between the three groups. The diagnosis of ED was based on detailed sexual
      history, physical examination, laboratory assessment and color Doppler
      ultrasonography and is defined as the inability to attain or maintain a penile
      erection that is sufficient for successful vaginal intercourse. The results are
      given as mean +/- s.d. of the mean. The mean age of the patients with
      vasculogenic ED, of patients with ED after radical prostatectomy and of the
      control group were 53.70 +/- 12.39 (range 24-77), 54.60 +/- 11.40 (range 43-61)
      and 53.85 +/- 9.5 (range 30-73), respectively (P = 0.853). The MPV and PLT values
      were significantly higher in patients with vasculogenic ED than in patients with
      ED after radical prostatectomy and in control groups: 7.49 +/- 1.4, 6.43 +/- 1.19
      and 6.85 +/- 1.2 for MPV and 262.97 +/- 68, 251.77 +/- 78 and 252.89 +/- 82 for
      PLT values, respectively (P = 0.033). The MPV and PLT values were not
      statistically significant in postprostatectomy ED patients and in control groups
      (P = 0.663). There was no significant difference among the three groups in terms
      of white blood cells and hemoglobin levels. PLT count and mean PLT volume were
      detected to be increased in patients with vasculogenic ED. This finding may
      suggest a role for PLT volume in the pathogenesis of vasculogenic ED.

PMID- 24871682
TI  - The Potion: Reflections on Freud's "Observations on Transference-Love"
AB  - This essay treats Freud's "Observations on Transference-Love," written a hundred
      years ago, as the quintessential psychoanalytic document, defining the clinical
      setup, charting its dangers, and providing ethical precepts for guiding
      treatment. Above all, in the context of those ethical questions, Freud's paper
      confronts the immense power and necessary strangeness of the transference-that
      form of love, or erotic bond, that fuels the healing process. The "potion"-an
      artificial yet powerfully real attachment-is the agent of a temporary induced
      blindness that gives access to a region otherwise inaccessible. A dream is
      presented to demonstrate that process. Freud, in describing this incendiary
      arrangement, likens it to a fire in a theater. The fire, the author proposes, is
      in the script.

PMID- 24871681
TI  - Cystatin C for glomerular filtration rate estimation: coming of age.

PMID- 24871683
TI  - Tuning phase stability of complex oxide nanocrystals via conjugation.
AB  - Nanocrystals (NCs) attract tremendous research interests because of their unique
      properties to meet the demands of functionalities. To date, hybrid NCs with
      multiple components are developed to meet the rising demands that could be very
      difficult, or even impossible to be achieved by single-component NCs. Tuning
      properties by strain via conjugation could be an alternative solution. Strain
      engineering has been discovered and widely applied to many thin-film materials
      for tuning physical properties. Then, there is a further question to be addressed
      in this study: can we take the advantages we have learned in heteroepitaxy of
      thin films and transfer that into the NC conjugation? In order to demonstrate
      this possibility, we investigated NC conjugation of BiFeO3 and LaAlO3. We found
      that change in either LaAlO3-NC or BiFeO3-NC size would change the stability of
      rhombohedral-to-tetragonal phase transition. The present results show that strain
      engineering is possible to be realized in not only thin film but also NC
      conjugation. The same concept should be applicable to other complex oxide systems
      in order to broaden their practical applications for the rising demands of
      multifunctionalities. 

PMID- 24871684
TI  - Relationship of skin autofluorescence to severity of retinopathy in type 2
      diabetes.
AB  - PURPOSE: To evaluate the relationship between skin autofluorescence (SAF), which
      reflects the accumulation of advanced glycation end products (AGEs), and the
      severity of diabetic retinopathy (DR) in patients with type 2 diabetes. METHODS:
      Sixty-seven eyes of 67 patients with type 2 diabetes were enrolled. Sixty-seven
      age-matched non-diabetic subjects served as controls. Diabetic patients were
      classified by the severity of their DR: no DR (NDR), non-proliferative DR (NPDR),
      and proliferative DR (PDR). SAF was measured with an autofluorescence reader.
      RESULTS: SAF in the diabetes patients was significantly higher than in the
      controls (median 2.5 (interquartile range 2.3-2.7) and 1.8 (1.6-2.3) arbitrary
      unit (AU), respectively, p < 0.001). There was a statistically significant
      increase in SAF along with the increasing severity of DR (from NDR to NPDR: p =
      0.034; NPDR to PDR: p < 0.01). Logistic regression analysis revealed that SAF
      (OR, 17.2; p < 0.05) was an independent factor indicating the presence of PDR.
      CONCLUSIONS: SAF has an independent relationship with PDR in patients with type 2
      diabetes. SAF measurement with an autofluorescence reader is a non-invasive way
      to assess the risk of DR. SAF may, therefore, be a surrogate marker candidate for
      the non-invasive evaluation of DR.

PMID- 24871685
TI  - Diffusion and dynamics of gamma-globulin in crowded aqueous solutions.
AB  - Dynamics in protein solutions is essential for both protein function and cellular
      processes. The hierarchical complexity of global protein diffusion, side-chain
      diffusion, and microscopic motions of chemical groups renders a complete
      understanding challenging. We present results from quasi-elastic neutron
      scattering on protein solutions of gamma-globulin over a wide range of volume
      fractions. Translational and rotational diffusion can be self-consistently
      separated from internal motions. The global diffusion is consistent with
      predictions for effective spheres even though the branched molecular shape
      differs considerably from a colloidal sphere. The internal motions are
      characterized both geometrically and dynamically, suggesting a picture of methyl
      rotations and restricted diffusion of side chains. We show that the advent of new
      neutron spectrometers allows the study of current questions including the
      coupling of intracellular dynamics and protein function. 

PMID- 24871686
TI  - Insights into an intriguing gas sorption mechanism in a polar metal-organic
      framework with open-metal sites and narrow channels.
AB  - Simulations of H2 and CO2 sorption were performed in the metal-organic framework
      (MOF), [Cu(Me-4py-trz-ia)]. This MOF was recently shown experimentally to exhibit
      high uptake for H2 and CO2 sorption and this was reproduced and elucidated
      through the simulations performed herein. Consistent with experiment, the
      theoretical isosteric heat of adsorption, Q(st), values were nearly constant
      across all loadings for both sorbates. The simulations revealed that sorption
      directly onto the open-metal sites was not observed in this MOF, ostensibly a
      consequence of the low partial positive charges of the Cu(2+) ions as determined
      through electronic structure calculations. Sorption was primarily observed
      between adjacent carboxylate oxygen atoms (site 1) and between nearby methyl
      groups (site 2) of the organic linkers. In addition, saturation of the most
      energetically favorable sites (site 1) is possible only after filling a nearby
      site (site 2) first due to the MOF topology. This suggests that the lack of
      dependence on loading for the Q(st) is due to the concurrent filling of sites 1
      and 2, leading to an observed average Q(st) value.

PMID- 24871687
TI  - RNA-peptide conjugate synthesis by inverse-electron demand Diels-Alder reaction.
AB  - Here we report an efficient method for the synthesis of RNA-peptide conjugates by
      inverse-electron demand Diels-Alder reaction. Various dienophiles were
      enzymatically incorporated into RNA and reacted with a chemically synthesized
      diene-modified peptide. The Diels-Alder reaction proceeds with near-quantitative
      yields in aqueous solution with stoichiometric amounts of reactants, even at low
      micromolar concentrations. 

PMID- 24871688
TI  - Tb(3+)-containing supramolecular hydrogels: luminescence properties and
      reversible sol-gel transitions induced by external stimuli.
AB  - A dual-responsive green-light-emitting supramolecular metal hydrogel (G-gel) was
      prepared by the reaction of a simple hydrazide-functionalized benzimidazole
      ligand (L) with Tb(NO3)3. The green luminescence of gelator L is enhanced in the
      G-gel due to the coordination effect between L and Tb(3+). In addition, the G-gel
      shows different luminescence when in a semisolid state (gel) and in a solid state
      (xerogel). Remarkable reversible sol-gel transitions induced by temperature or pH
      were observed for this G-gel. 

PMID- 24871689
TI  - Intraoperative anaphylactic reaction IV degrees  to gelatin.

PMID- 24871690
TI  - Micro-computed tomography evaluation of the removal of calcium hydroxide
      medicament from C-shaped root canals of mandibular second molars.
AB  - AIM: To use micro-computed tomography (MU-CT) to evaluate the amount of calcium
      hydroxide [Ca(OH)2 ] remaining in the C-shaped root canals of mandibular second
      molars after attempting to remove it with passive ultrasonic and sonic
      irrigation. METHODOLOGY: Thirty mandibular second molars, 15 in C1 and 15 in C2
      configurations as first identified by MU-CT, were divided into three groups (five
      C1 and five C2 in each group) for the three irrigation methods. All teeth were
      prepared to ProTaper Universal F2 and filled with Ca(OH)2 paste. The Ca(OH)2 was
      removed with F2 files and irrigation without agitation or with agitation using
      either EndoActivator or ultrasonics. MU-CT was used to measure the initial amount
      of Ca(OH)2 present. After removal of Ca(OH)2, MU-CT imaging was used to assess
      the percentage of volume of residual Ca(OH)2 in the canal. Data were analysed
      using one-way anova test. RESULTS: There was no significant difference in the
      mean volume of the root canal systems after instrumentation amongst the three
      groups. The three irrigation techniques left 2-17% of Ca(OH)2 in the root canals
      after removal. The mean volume of the remaining Ca(OH)2 was higher in the group
      without agitation than in the groups with sonic or ultrasonic agitation (P <
      0.05). In the apical third, 68% of the canal space remained occupied by Ca(OH)2
      when no agitation was used, whereas 28% and 31% remained filled by Ca(OH)2 in the
      EndoActivator and ultrasonic groups, respectively. There was no significant
      difference in the amount of residual Ca(OH)2 between the EndoActivator and
      ultrasonic groups. The proportion of remaining Ca(OH)2 in the apical canals was
      higher than in the middle and coronal canals in all groups (P < 0.05).
      CONCLUSIONS: A considerable proportion of the apical canal space remained filled
      with Ca(OH)2 in the C-shaped root canals after instrumentation and conventional
      needle irrigation. Although combining rotary instrumentation and irrigation with
      sonic or ultrasonic agitation reduced the amount of residual Ca(OH)2 in the C
      shaped root canals, the large amount of calcium hydroxide in the critical apical
      area remains a concern. Alternative strategies should be considered in medication
      of the apical canal in C-shaped teeth.

PMID- 24871692
TI  - Comparing Client Outcomes for Two Evidence-Based Treatment Consultation
      Strategies.
AB  - Posttraining expert case consultation is a key component of transporting and
      scaling up evidence-based treatments, and hopefully retaining their efficacy.
      Live practice observation and in vivo coaching is a strategy used in academic
      training environments, but is rarely feasible in field settings. Post hoc
      telephone consultation is a substitute strategy but does not approximate many
      aspects of live coaching. Live video technology offers a closer approximation but
      has not yet been sufficiently tested. Using a roll-out experimental design, this
      study compared client outcomes across doses of two posttraining expert
      consultation strategies-standard telephone consultation and live video coaching.
      The study was conducted during a two-state, 30-agency implementation involving 80
      therapists and 330 cases receiving Parent-Child Interaction Therapy (PCIT). Child
      behavior problems fell from well above to below clinical cutoff values, with
      about a 1 standard deviation improvement in 14 sessions, which is within the
      range reported in laboratory efficacy trials. Symptom improvement was augmented
      by increased therapist dose of live video consultations. Phone consultation dose
      had no association with client level outcomes. PCIT benefits appear to be
      retained when the model is transported at scale into the field, and live video
      consultation appeared to offer small but significant advantages over telephone
      consultation as one element of an overall transport strategy. 

PMID- 24871693
TI  - Immunoregulatory activity of adenosine and its role in human cancer progression.
AB  - The adenosinergic pathway plays an important role in cancer progression. Aside
      from regulating functions of tumor cells and tissue cells present in the tumor
      microenvironment, extracellular adenosine is an autocrine or paracrine factor
      with powerful immunoregulatory activity. Adenosine signaling downregulates
      functions of most immune effector cells but enhances expansion and activity of
      immune cells responsible for suppression of anti-tumor immune responses.
      Adenosine is critical for limiting potential tissue-destructive effects of
      activated immune cells. It also facilitates tumor escape from the immune control.
      This review illustrates the involvement of adenosine and its four receptors, A1R,
      A2AR, A2BR and A3R, in the complex regulation of cellular and molecular cross
      talk that contributes to cancer progression. It also considers the potential of
      therapeutics targeting the adenosinergic pathway for benefiting cancer patients.

PMID- 24871695
TI  - Evaluation of portal hypertension and varices by acoustic radiation force impulse
      imaging of the liver compared to transient elastography and AST to platelet ratio
      index.
AB  - BACKGROUND: Acoustic radiation force impulse imaging (ARFI) is a new method of
      liver stiffness measurement (LSM). The aim was to compare ARFI, transient
      elastography (TE) and AST to platelet ratio index (APRI) for the noninvasive
      diagnosis of clinically significant portal hypertension (CSPH, hepatic venous
      pressure gradient; HVPG >= 10 mmHg) and esophageal varices (EV). MATERIALS AND
      METHODS: LSM via ARFI and TE was performed in 88 consecutive patients with
      cirrhosis prior to HVPG measurement. The mean liver stiffness for ARFI was
      calculated out of 5 measurements for each lobe. RESULTS: LSM by TE and ARFI was
      not successful in 22 (25%) patients and 1 (1 %) patient, respectively, due to
      ascites or obesity. Both TE (r = 0.765; p < 0.001) and ARFI (r = 0.646; p <
      0.001) correlated significantly with HVPG. At the optimal cut-off (16.8 kPa), TE
      (area under the curve, AUC 0.870) yielded a sensitivity and specificity of 89.7%
      and 75%, respectively, for predicting CSPH. At the optimal cut-off (2.58 m/s),
      the sensitivity and specificity for ARFI (AUC 0.855) were 71.4% and 87.5%,
      respectively. Using an APRI (AUC 0.838), the sensitivity and specificity were 69%
      and 87.5%, respectively. The AUC for the diagnosis of EV was 0.802 for TE (cut
      off: 27.9 kPa), 0.743 for ARFI (cut-off: 2.74 m/s), and 0.805 for APRI (cut-off:
      1.90). CONCLUSION: ARFI shows a higher applicability particularly in obese and
      ascitic patients. All three investigated methods show a high diagnostic accuracy
      for CSPH. Notably, APRI performed not significantly different compared to ARFI
      for the diagnosis of CSPH.

PMID- 24871694
TI  - Detection of microcalcifications in women with dense breasts and hypoechoic focal
      lesions: comparison of mammography and ultrasound.
AB  - PURPOSE: Microcalcifications in the breasts can point to breast cancer. However,
      there is great morphologic variety, and microcalcifications do not always
      correlate with malignancy. We conducted a prospective study to compare ultrasound
      and mammography in the detection of microcalcifications following sonographic
      diagnosis of a hypoechoic focal lesion in women with dense breast composition.
      MATERIALS AND METHODS: A total of 104 lesions potentially associated with
      microcalcifications (82 malignant and 23 benign lesions) were included in the
      study. The breast was examined by ultrasound (9 MHz, Aplio XG/500) with
      additional use of MicroPure imaging for the demonstration and evaluation of
      microcalcifications. The presence of a focal lesion was verified and
      microcalcifications were counted at ultrasound and mammography by blinded
      readers. The sensitivity and specificity were determined, and ROC analysis and
      AUC analysis were performed. RESULTS: The women had a median age of 51 years. The
      average number of microcalcifications detected by sonography (2.12 +/- 2.77) and
      mammography (3.59 +/- 6.35) was not significantly different (p > 0.05).
      Correlation of the techniques was adequate (Pearson's r = 0.616, p < 0.0001;
      Spearman's rho = 0.654, p < 0.0001). The intraclass correlation coefficient was K
      = 0.382 +/- 0.072 (p < 0.0001), also indicating adequate agreement of both
      techniques. The sensitivity and specificity were 70%/30% for MicroPure and
      45%/55% for mammography. The positive predictive value of mammography was
      superior to that of MicroPure (88% vs. 78%). CONCLUSION: The sonographic
      detection of microcalcifications with MicroPure imaging in breasts with a
      hypoechoic focal lesion correlates well with digital mammography.

PMID- 24871696
TI  - Molecular dynamics simulations of the structure of the graphene-ionic
      liquid/alkali salt mixtures interface.
AB  - We performed molecular dynamics simulations of mixtures of 1-butyl-3
      methylimidazolium tetrafluoroborate with lithium tetrafluoroborate and potassium
      tetrafluoroborate between two charged and uncharged graphene walls, in order to
      analyze the structure of the well-known formation of layers that takes place on
      liquids under confinement. For this purpose, we studied the molecular density
      profiles, free energy profiles for bringing lithium and potassium cations from
      the bulk mixture to the graphene wall and the orientational distributions of
      imidazolium rings within the first adsorbed layer as a function of salt
      concentration and electrode potential. The charge densities in the electrodes
      were chosen to be zero and +/-1 e nm(-2), and the salt molar percentages were
      %salt = 0, 10 and 25. We found that the layered structure extends up to 1-2 nm,
      where the bulk behaviour is recovered. In addition, whereas for the neutral
      surface the layers are composed of both ionic species, increasing the electrode
      potential, the structure changes to alternating cationic and anionic layers
      leading to an overcompensation of the charge of the previous layer. We also
      calculated the distribution of angles of imidazolium rings near neutral and
      charged graphene walls, finding a limited influence of the added salt. In
      addition, the average tilt of the imidazolium ring within the first layer goes
      from 36 degrees  with respect to a normal vector to the uncharged graphene wall
      to 62 degrees  in the presence of charged walls. The free energy profiles
      revealed that lithium and potassium ions are adsorbed on the negative surface
      only for the highest amount of salt, since the free energy barriers for
      approaching this electrode are considerably higher than kBT. 

PMID- 24871697
TI  - Flocculation of Escherichia coli using a quaternary ammonium salt grafted
      carboxymethyl chitosan flocculant.
AB  - Only few studies are available on bacteria removal efficiencies and antibacterial
      properties of flocculants, which is one of the important requirements in water
      treatment work. Escherichia coli (E. coli) was selected as an example of a Gram
      negative bacteria for testing the flocculating properties of a quaternary
      ammonium salt grafted chitosan (carboxymethyl chitosan-graft-poly[(2
      methacryloyloxyethyl) trimethylammonium chloride] copolymer; i.e., CMC-g-PDMC).
      The effect of various flocculation parameters, including flocculant dosage,
      initial bacterial density, nutrient medium content, and pH were successively
      investigated. The experimental results indicated that, besides flocculation
      effects, CMC-g-PDMC also exhibited a bactericidal effect (not requiring
      additional treatment facilities). Moreover, the flocculation mechanisms were
      investigated via zeta potential measurements, floc observation, and three
      dimensional excitation-emission matrix spectra analysis. Apart from its
      flocculating and settling effect, this chitosan-based material has bactericidal
      action through the breaking of bacterial cell walls by grafted quaternary
      ammonium salt. 

PMID- 24871698
TI  - The use of magnetic resonance imaging in the diagnosis of suspected appendicitis
      in pregnancy: shortened length of stay without increase in hospital charges.
AB  - IMPORTANCE: Making an accurate diagnosis of appendicitis in pregnancy is critical
      for maternal and fetal outcomes. OBJECTIVE: To determine whether magnetic
      resonance (MR) imaging in pregnant patients with suspected appendicitis improves
      outcomes, minimizes length of stay (LOS), and lowers hospital charges. DESIGN,
      SETTING, AND PARTICIPANTS: Retrospective review at a university tertiary referral
      center of all pregnant patients seen with abdominal pain and suspected
      appendicitis who were followed up through delivery during an 11-year period. MAIN
      OUTCOMES AND MEASURES: Time to operation, LOS, complications, nontherapeutic
      exploration, fetal outcomes, and hospital charges. RESULTS: Seventy-nine patients
      were included in this study, 34 of whom had pathology-confirmed appendicitis.
      Thirty-one patients underwent MR imaging. A trend toward fewer operations (odds
      ratio [OR], 0.45; 95% CI, 0.18-1.16; P = .07) was observed in the MR imaging
      group. Seven nontherapeutic explorations were performed in the non-MR imaging
      group and 1 nontherapeutic exploration in the MR imaging group (OR, 0.44; 95% CI,
      0.08-2.32; P = .13). Patients in the MR imaging group were more frequently
      discharged from the emergency department (OR, 0.35; 95% CI, 0.13-0.94; P = .04)
      and had shorter LOS (33.7 vs 64.8 hours, P < .001). Gestational age, time to
      operation, and the presence of perforated appendicitis were similar between
      groups. No patient discharged without operation returned with appendicitis in
      either group. On multivariable analysis, the receipt of MR imaging (P < .001) and
      the absence of operative intervention (P = .001) were associated with shorter
      LOS. The mean hospital charges were similar in those with vs without
      appendicitis. One fetal loss occurred in the non-MR imaging group. CONCLUSIONS
      AND RELEVANCE: Magnetic resonance imaging in pregnant patients with suspected
      appendicitis does not affect clinical outcomes or hospital charges. It allows
      safe discharge from the emergency department and improves resource use.

PMID- 24871699
TI  - NMDA receptor blockade in the prelimbic cortex activates the mesolimbic system
      and dopamine-dependent opiate reward signaling.
AB  - RATIONALE: N-Methyl-D-aspartate (NMDA) receptors in the medial prefrontal cortex
      (mPFC) are involved in opiate reward processing and modulate sub-cortical
      dopamine (DA) activity. NMDA receptor blockade in the prelimbic (PLC) division of
      the mPFC strongly potentiates the rewarding behavioural properties of normally
      sub-reward threshold doses of opiates. However, the possible functional
      interactions between cortical NMDA and sub-cortical DAergic motivational neural
      pathways underlying these effects are not understood. OBJECTIVE: This study
      examines how NMDA receptor modulation in the PLC influences opiate reward
      processing via interactions with sub-cortical DAergic transmission. We further
      examined whether direct intra-PLC NMDA receptor modulation may activate DA
      dependent opiate reward signaling via interactions with the ventral tegmental
      area (VTA). METHODS: Using an unbiased place conditioning procedure (CPP) in
      rats, we performed bilateral intra-PLC microinfusions of the competitive NMDA
      receptor antagonist, (2R)-amino-5-phosphonovaleric acid (AP-5), prior to
      behavioural morphine place conditioning and challenged the rewarding effects of
      morphine with DA receptor blockade. We next examined the effects of intra-PLC
      NMDA receptor blockade on the spontaneous activity patterns of presumptive VTA DA
      or GABAergic neurons, using single-unit, extracellular in vivo neuronal
      recordings. RESULTS: We show that intra-PLC NMDA receptor blockade strongly
      activates sub-cortical DA neurons within the VTA while inhibiting presumptive non
      DA GABAergic neurons. Behaviourally, NMDA receptor blockade activates a DA
      dependent opiate reward system, as pharmacological blockade of DA transmission
      blocked morphine reward only in the presence of intra-PLC NMDA receptor
      antagonism. CONCLUSIONS: These findings demonstrate a cortical NMDA-mediated
      mechanism controlling mesolimbic DAergic modulation of opiate reward processing.

PMID- 24871700
TI  - Quantification of ten neuroactive steroids in plasma in Withdrawal Seizure-Prone
      and -Resistant mice during chronic ethanol withdrawal.
AB  - RATIONALE: The rapid membrane actions of neuroactive steroids, particularly via
      an enhancement of gamma-aminobutyric acidA receptors (GABAARs), participate in
      the regulation of central nervous system excitability. Prior evidence suggests an
      inverse relationship between endogenous GABAergic neuroactive steroid levels and
      behavioral changes in excitability during ethanol withdrawal. OBJECTIVES:
      Previously, we found that ethanol withdrawal significantly decreased plasma
      allopregnanolone (ALLO) levels, a potent GABAergic neuroactive steroid, and
      decreased GABAAR sensitivity to ALLO in Withdrawal Seizure-Prone (WSP) but not in
      Withdrawal Seizure-Resistant (WSR) mice. However, the effect of ethanol
      withdrawal on levels of other endogenous GABAAR-active steroids is not known.
      METHODS: After validation of a gas chromatography-mass spectrometry method for
      the simultaneous quantification of ten neuroactive steroids, we analyzed plasma
      from control male WSP-1 and WSR-1 mice and during ethanol withdrawal. RESULTS: We
      quantified levels of nine neuroactive steroids in WSP-1 and WSR-1 plasma; levels
      of pregnanolone were not detectable. Basal levels of five neuroactive steroids
      were higher in WSR-1 versus WSP-1 mice. Ethanol withdrawal significantly
      suppressed five neuroactive steroids in WSP-1 and WSR-1 mice, including ALLO.
      CONCLUSIONS: Due to lower basal levels of some GABAAR-active steroids in WSP-1
      mice, a withdrawal-induced decrease in WSP-1 mice may have a greater
      physiological consequence than a similar decrease in WSR-1 mice. Because WSP-1
      mice also exhibit a reduction in GABAAR sensitivity to neuroactive steroids
      during withdrawal, it is possible that the combined decrease in neuroactive
      steroids and GABAAR sensitivity during ethanol withdrawal in WSP-1 mice
      represents a neurochemical substrate for severe ethanol withdrawal.

PMID- 24871702
TI  - Consideration of a comprehensive animal model of addiction: the limitations of
      modeling a counterfeit condition.

PMID- 24871701
TI  - A study of antioxidant activity in patients with schizophrenia taking atypical
      antipsychotics.
AB  - INTRODUCTION: Atypical antipsychotics have significantly improved the quality of
      life for schizophrenic patients. Despite their beneficial effects, these
      antipsychotics induce weight gain, diabetes, and dyslipidemia. The aims of this
      study were to investigate the antioxidative activity of paraoxonase and assess
      lipid profile as a cardiovascular risk factor in patients with schizophrenia
      under long-term clozapine or risperidone treatment. METHODS: The study included
      66 patients with schizophrenia under clozapine or risperidone treatment and 19
      healthy control subjects. Serum paraoxonase activities against paraoxon
      (PON(PO)), phenylacetate (PON(PA)), dihydrocoumarin (PON(DHC)), serum Trolox
      equivalent antioxidant activity (TEAC), antioxidant gap (GAP), and lipid profile
      were determined. RESULTS: PON(DHC) activity was reduced in both antipsychotic
      drug-treated groups (clozapine 43.46 +/- 1.06 U/ml, p < 0.001; risperidone 50.57
      +/- 1.54 U/ml, p < 0.01; control 52.27 +/- 1.34 U/ml). A similar pattern was
      observed for the PON(DHC)/HDL-cholesterol (HDLC) ratio. On the contrary, PON(PO)
      and PON(PA) were increased in the treated group, but the corresponding
      paraoxonase/HDLC ratios were not significantly different from controls, except
      for PON/HDLC in the clozapine group. TEAC and GAP were only decreased in the
      clozapine-treated group. CONCLUSIONS: In patients with schizophrenia, clozapine
      or risperidone treatment had different effects on various paraoxonase activities.
      The results of the present study suggest that patients with schizophrenia might
      be at increased risk for metabolic and cardiovascular disease related to reduced
      PON(DHC), TEAC, and GAP.

PMID- 24871704
TI  - The efficacy and safety of 5 mg/d Vortioxetine compared to placebo for major
      depressive disorder: A meta-analysis.
AB  - OBJECTIVE: This meta-analysis assessed the efficacy and safety of 5 mg/day
      vortioxetine compared to placebo for adult major depressive disorder. METHODS: We
      performed a meta-analysis of the double-blind, randomized, controlled clinical
      trials involving 5 mg/day vortioxetine in adult patients with major depressive
      disorder published on PubMed, EBSCO, and PsycINFO, and the Clinical Trials
      databases were searched from 2000 through October 2013. The abstracts for the
      Annual Meetings of the American Psychiatric Association (APA) and previous
      reviews were searched to identify additional studies. Results were expressed with
      odds ratios (ORs) with their 95 % confidence interval (CI). The effect size (ES)
      for the four studies was derived by computing the standardized mean difference
      (SMD). The data were pooled with a random effects model. RESULTS: Five RCTs met
      the selection criteria. Results of the meta-analysis showed the following: (1)
      The treatment response of 5 mg/day vortioxetine group was greater than placebo
      group (OR=1.84, 95 % CI=1.16-2.93, Z=2.59, P=0.010), and there was a significant
      antidepressant effect of vortioxetine (ES=2.98, P=0.001). However, there was no
      significant difference in remission (OR=1.47, 95 % CI=0.95-2.30, Z=1.71,
      P=0.090). (2) The common adverse effects included nausea, dizziness, headache,
      dry mouth, and diarrhea. There was a significant difference for nausea between
      the two groups (OR=3.01, 95 % CI=2.22-4.09, Z=7.08, P=0.00001), but no
      significant differences were observed for the other four adverse effects.
      CONCLUSIONS: For the treatment of major depressive disorder, our results show
      that a dose of 5 mg/day vortioxetine was more effective, but more easily induced
      nausea, compared to placebo.

PMID- 24871703
TI  - The beneficial effect of oxytocin on avoidance-related facial emotion recognition
      depends on early life stress experience.
AB  - RATIONALE: Previous studies have shown that oxytocin (OXT) enhances social
      cognitive processes. It has also been demonstrated that OXT does not uniformly
      facilitate social cognition. The effects of OXT administration strongly depend on
      the exposure to stressful experiences in early life. Emotional facial recognition
      is crucial for social cognition. However, no study has yet examined how the
      effects of OXT on the ability to identify emotional faces are altered by early
      life stress (ELS) experiences. Given the role of OXT in modulating social
      motivational processes, we specifically aimed to investigate its effects on the
      recognition of approach- and avoidance-related facial emotions. METHODS: In a
      double-blind, between-subjects, placebo-controlled design, 82 male participants
      performed an emotion recognition task with faces taken from the "Karolinska
      Directed Emotional Faces" set. We clustered the six basic emotions along the
      dimensions approach (happy, surprise, anger) and avoidance (fear, sadness,
      disgust). ELS was assessed with the Childhood Trauma Questionnaire (CTQ).
      RESULTS: Our results showed that OXT improved the ability to recognize avoidance
      related emotional faces as compared to approach-related emotional faces. Whereas
      the performance for avoidance-related emotions in participants with higher ELS
      scores was comparable in both OXT and placebo condition, OXT enhanced emotion
      recognition in participants with lower ELS scores. Independent of OXT
      administration, we observed increased emotion recognition for avoidance-related
      faces in participants with high ELS scores. CONCLUSIONS: Our findings suggest
      that the investigation of OXT on social recognition requires a broad approach
      that takes ELS experiences as well as motivational processes into account.

PMID- 24871707
TI  - Electronic publication in zoological nomenclature and taxonomy: problems,
      responses and solutions.

PMID- 24871706
TI  - Genomic and transcriptomic analyses match medulloblastoma mouse models to their
      human counterparts.
AB  - Medulloblastoma is a malignant embryonal brain tumor with highly variable
      outcome. In order to study the biology of this tumor and to perform preclinical
      treatment studies, a lot of effort has been put into the generation of
      appropriate mouse models. The usage of these models, however, has become
      debatable with the advances in human medulloblastoma subgrouping. This study
      brings together multiple relevant mouse models and matches genetic alterations
      and gene expression data of 140 murine tumors with 423 human medulloblastomas in
      a global way. Using AGDEX analysis and k-means clustering, we show that the Blbp
      cre::Ctnnb1(ex3)(Fl/+)Trp53 (Fl/Fl) mouse model fits well to human WNT
      medulloblastoma, and that, among various Myc- or Mycn-based mouse
      medulloblastomas, tumors in Glt1-tTA::TRE-MYCN/Luc mice proved to be most
      specific for human group 3 medulloblastoma. None of the analyzed models displayed
      a significant match to group 4 tumors. Intriguingly, mice with Ptch1 or Smo
      mutations selectively modeled SHH medulloblastomas of adulthood, although such
      mutations occur in all human age groups. We therefore suggest that the infantile
      or adult gene expression pattern of SHH MBs are not solely determined by specific
      mutations. This is supported by the observation that human medulloblastomas with
      PTCH1 mutations displayed more similarities to PTCH1 wild-type tumors of the same
      age group than to PTCH1-mutated tumors of the other age group. Together, we
      provide novel insights into previously unrecognized specificity of distinct
      models and suggest these findings as a solid basis to choose the appropriate
      model for preclinical studies on medulloblastoma.

PMID- 24871705
TI  - Methylnaltrexone: its pharmacological effects alone and effects on morphine in
      healthy volunteers.
AB  - RATIONALE: Methylnaltrexone bromide (MTNX) is a peripherally acting mu-opioid
      receptor antagonist, prescribed for the treatment of opioid-induced constipation
      in patients with advanced illness who are receiving palliative care. Studies have
      used this drug to determine if other opioid-induced effects besides constipation
      are altered by MTNX in humans and have suggested, based on their results, that
      these other effects are altered by peripheral opioid actions. OBJECTIVE: The
      primary objective of this report is to present results that provide indirect
      evidence that MTNX has centrally mediated effects, albeit slight, and secondarily
      to describe the effects of MTNX on psychopharmacological effects of morphine.
      METHODS: In a crossover, randomized, placebo-controlled, double-blind study, 29
      healthy volunteers received 0.45 mg/kg MTNX or saline subcutaneously, followed by
      saline intravenously. In three other conditions, 0.143 mg/kg of morphine sulfate
      administered intravenously was preceded by subcutaneous administration of 0,
      0.225, or 0.45 mg/kg MTNX. Before and after drug administration, subjective and
      physiological measures, including pupil diameter, were assessed. RESULTS: Two
      separate analyses confirmed that 0.45 mg/kg MTNX alone induced a slight degree of
      miosis, a centrally mediated opioid agonist effect. This dose had minimal
      subjective effects. MTNX at either or both the 0.225 and 0.45 mg/kg dose reduced
      some subjective effects of morphine without altering miosis. CONCLUSIONS: We
      present indirect evidence that MTNX crosses the blood-brain barrier in humans.
      Therefore, whether the reductions in subjective effects of morphine by MTNX that
      were observed in past studies and in this study can be attributed to peripheral
      mechanisms is open to question.

PMID- 24871708
TI  - Zoological Nomenclature and Electronic Publication-a reply to Dubois et al.
      (2013).

PMID- 24871709
TI  - Online-only publishers are here to stay, and will continue to work closely with
      the ICZN.

PMID- 24871710
TI  - Alafrasca sticta, a new genus and species of the tribe Empoascini (Hemiptera:
      Cicadellidae: Typhlocybinae) with a checklist of the tribe from China.
AB  - A new monotypic genus of empoascine leafhopper, Alafrasca gen. nov. is described
      and illustrated for A. sticta sp. nov. from Sichuan, China as its type species.
      Habitus photos and illustrations of male genitalia of the new species are given.
      A checklist of the tribe in China is also provided. 

PMID- 24871711
TI  - Review of the Diplazontinae (Hymenoptera, Ichneumonidae) of the Kuril islands,
      with descriptions of two new species.
AB  - A sample of 346 specimens of Diplazontinae parasitoid wasps from the Kuril
      islands was studied. Twenty-six species are reported, Tymmophorus gelidus Dasch
      for the first time for the Eastern Palaearctic. Two new species are described,
      Diplazon kurilensis sp. n. and Homotropus formosus sp. n. Diplazon urupensis
      Uchida is removed from synonymy (stat. rev.), and Promethes persulcatus Nakanishi
      is suggested as a synonym of Promethes bridgmani Fitton. Reasons are discussed
      for the large proportion of species with a Holarctic or even multi-regional
      distribution in the sample, which amounts to17 of the species or 65%. 

PMID- 24871712
TI  - First record of the genus Australonura Cassagnau 1980 (Collembola: Neanuridae) in
      the New World, with description of a new species from Paraguay.
AB  - The genus Australonura Cassagnau 1980 is newly recorded from South America. The
      Patagonian species Paleonura limnophila (Cassagnau & Rapoport, 1962) and
      Paleonura friasica Cassagnau & Oliveira, 1990 are redescribed from type material
      and recombined in Australonura. A new species, A. paraguayensis sp. nov., is
      described from Paraguay and assigned to Australonura for its head tubercle
      arrangement. It differs from other species of the genus by its adjacent but
      separate dorso-internal tubercles of Abd. V. 

PMID- 24871713
TI  - The genus Triozocera Pierce, 1909 (Insecta: Strepsiptera: Corioxenidae) in South
      America.
AB  - A new species of Triozocera from the Brazilian Amazon basin was found in a sample
      of male Strepsiptera from the collection of the Instituto Nacional de Pesquisas
      da Amazonia (INPA-Manaus, Amazonas, Brazil). Triozocera buehrheimi sp.n. is
      described and the status of T. paulistana Kogan, 1958, the first strepsipteran
      described from Brazil, is reviewed, with additional diagnostic characters used to
      reinstate the species based on comparative analyses to the other three species
      occurring in southern US, Mexico, and Central America: T. mexicana Pierce, 1909,
      T. tecpanensis Brailowsky and Marquez, 1974, and T. vernalis Kifune and
      Brailowsky, 1987. A key to those species is included. 

PMID- 24871714
TI  - The genus Cerithideopsis Thiele, 1929 (Gastropoda: Potamididae) in the Indo-West
      Pacific region.
AB  - The genus Cerithideopsis is most common in mangrove and salt marsh habitats of
      the New World tropics, but there is also a small radiation in the Indo-West
      Pacific region. Previously, these Indo-Pacific snails have generally been
      classified as Cerithidea largillierti (Philippi, 1848). Molecular phylogenetic
      analysis (partial sequences of mitochondrial COI and 16S rRNA, and nuclear 28S
      rRNA) of 15 specimens from 8 localities between Japan and Australia reveal three
      clades, among which there are small morphological differences and which show
      allopatric distributions. Cerithideopsis largillierti sensu stricto is restricted
      to Japan and China, while the two other species are described as new: C.
      australiensis occurs in tropical Australasia and C. malayensis is found from
      Malaysia to Java and the Philippines. All occur on mud and in pools with leaf
      litter, in the shaded landward and middle zones of mangrove forests, and do not
      climb the trees. The species accounts include full synonymies, detailed
      descriptions of shells based on 82 museum samples, descriptions of living
      animals, distribution records and maps, and notes on habitat and conservation
      status. 

PMID- 24871715
TI  - Stoneflies (Insecta: Plecoptera) from Serra Bonita, Bahia, Brazil: new species
      and updated records.
AB  - There are 176 species representing eight genera and two families of Plecoptera
      known from Brazil. However, only ten of these species are recorded from the State
      of Bahia. In this study, an inventory of stoneflies from the southern region of
      Bahia State, Serra Bonita, including the municipality of Camacan, was undertaken
      from 2007-2012. Stoneflies were collected using UV light pan traps, Malaise
      traps, and aerial nets. One new gripopterygid species, Tupiperla bispoi n. sp.,
      is described and illustrated. Four genera representing ten other species are
      recorded: Gripopteryx cancellata, G. clemira, G. garbei, G. pinima,
      Paragripopteryx sp., and Tupiperla tessellata (Gripopterygidae), Kempnyia
      alterosarum, K. gracilenta, K. jatim, and K. neotropica (Perlidae). With the
      present study, the number of known species of stoneflies recorded from Bahia
      State is 17, ten of these recorded from the Serra Bonita region.

PMID- 24871716
TI  - Larval morphology and advertisement call of Phyllodytes acuminatus Bokermann,
      1966 (Anura: Hylidae) from Northeastern Brazil.
AB  - This paper describes the tadpole and advertisement call of Phyllodytes
      acuminatus, based on specimens from the Parque Nacional do Catimbau, in the
      municipality of Buique, State of Pernambuco, Northeastern Brazil. The overall
      morphology of P. acuminatus tadpole is similar to that of most species of the
      genus. The presence of a double row of marginal papillae surrounding all the oral
      apparatus (except on most of the upper labium which has a dorsal gap) was a
      characteristic that differentiate P. acuminatus from the other species of the
      genus. Furthermore, the call structure of the species (unpulsed notes with
      harmonic structure) fits it in the group composed of P. kautskyi and P.
      melanomystax. 

PMID- 24871717
TI  - Complementary redescription of Anacanthobatis ori (Wallace, 1967) and its
      assignment to Indobatis n. g. (Elasmobranchii, Anacanthobatidae), with comments
      on other legskates.
AB  - Anacanthobatis ori is one of the least known species of the family
      Anacanthobatidae with only four juvenile specimens reported. The species remained
      assigned to the genus Anacanthobatis sensu lato due to the lack of an adult male
      as external and skeletal clasper characters are the essential diagnostic features
      for the differentiation of genera and subgenera within the family
      Anacanthobatidae. Since an adult male of A. ori became available, along with an
      adult female and six further juveniles, the authors reinvestigated the species
      and present its so far unknown diagnostic characters of clasper morphology and
      skeleton and scapulocoracoid. The clasper turned out to be the most complex one
      of all known anacanthobatids as the external components flag, slit, pseudosiphon
      like cavity, pecten, and two sentinas are not known from any other anacanthobatid
      species. Furthermore, a dorsal terminal 1 cartilage is present but displaced
      proximally of the terminal clasper skeleton, the outer edge of dorsal terminal 2
      is deeply serrated, the ventral terminal has a very long, curved, strap-like
      process, and the proximal part of accessory terminal 1 is embedded in the cavity
      of the baseball-glove-like head of accessory terminal 2. Due to the strong
      differences in external and internal clasper characters to all other known
      anacanthobatid species, A. ori is placed in its own, newly erected genus,
      Indobatis.  

PMID- 24871718
TI  - The centipedes (Arthropoda, Myriapoda, Chilopoda) from Colombia: Part I.
      Scutigeromorpha and Scolopendromorpha.
AB  - This study presents an updated list of centipedes of the orders Scutigeromorpha
      and Scolopendromorpha from Colombia based on data from the literature, the World
      Catalogue of Centipedes (CHILOBASE), and specimens examined in museum
      collections. Four families, nine genera, 37 species and four subspecies are
      listed. One species belongs to Scutigeromorpha, and 36 species and four
      subspecies to Scolopendromorpha. Eleven species and four subspecies of
      scolopendromorphs are recorded for the first time from Colombia. Newportia
      Gervais, 1847 is the most diverse genus with 12 species and three subspecies. Six
      species of Scolopendromorpha are endemic. Three species-Otostigmus inermis Porat,
      1876, O. scabricauda (Humbert & Saussure, 1870) and Cryptops iheringi Brolemann,
      1902-are deleted from the fauna of Colombia. The Andean Region in Colombia has
      the most records of Scutigeromorpha and Scolopendromorpha. Maps showing the
      geographical distribution are given for the orders, genera, and some species. 

PMID- 24871719
TI  - Neotropical Agromyzidae (Diptera) of the Mission Geodesique de l'Equateur: Becker
      (1920) revisited.
AB  - The Ecuadorian Agromyzidae described by Theodor Becker from the Mission du
      service geographique de l'armee pour la mesure d'un arc de meridien equatorial en
      Amerique du Sud are revised and several taxonomic changes are proposed. The eight
      named species identified by Becker actually comprise 14 species of Agromyzidae (3
      Melanagromyza, 4 Cerodontha, 6 Liriomyza, 1 Nemorimyza) and one species of
      Heleomyzidae. Three new species are described: Cerodontha (Cerodontha) angela
      Boucher sp. n.; Liriomyza biensis Boucher sp. n.; Melanagromyza pontis Boucher
      sp. n. New species records for Ecuador include Melanagromyza memoranda Spencer;
      M. lini Spencer; Cerodontha (C.) colombiensis Spencer; Liriomyza nigra Spencer
      and Nemorimyza fuscibasis (Malloch). Cerodontha (C.) nigricornis Becker is
      redescribed, including the first description of the male genitalia. Liriomyza
      biformata (Becker) is redescribed and two species are included as junior synonyms
      of L. biformata: Agromyza braziliensis Frost syn. n. and A. ecuadorensis Frost
      syn. n. Agromyza bipartita Becker is transferred to the family Heleomyzidae as
      Notomyza bipartita comb. n. 

PMID- 24871720
TI  - Comments on "the phylogeny of post-Palaeozoic Asteroidea (Neoasteroidea,
      Echinodermata)" by A.S. Gale and perspectives on the systematics of the
      Asteroidea.
AB  - A new, morphologically based classification of extant asteroids with comments on
      select fossils was published by A.S. Gale. Research approaches used limited
      sampling, and much literature treatment is not accurate and therefore misleading.
      We review these concerns, seeking to clarify argumentation on differing
      interpretations. 

PMID- 24871721
TI  - The Red Sea species of Cymo de Haan, 1833 (Decapoda, Brachyura, Xanthidae),
      associates of scleractinian corals.
AB  - Four species of Cymo, associates of scleractinian corals, from the Red Sea were
      studied using scanning electron and light microscopy. Characters based on the
      morphologies of the carapace, gonopods and digestive tract (gastric teeth) were
      investigated and described in detail. All Red Sea species are redescribed,
      distinguishing characters are identified and an identification key is provided.
      Cymo quadrilobatus is the most distinctive species, with prominent granules on
      the carapace and most of the surfaces of the chelipeds and walking legs, and four
      red spots on the dorsal surface of the carapace in contrast to the smooth or
      finely granular surfaces in the other three species. Cymo deplanatus is listed as
      new record for the Red Sea.  

PMID- 24871722
TI  - High diversity of Drosophilidae (Insecta, Diptera) in the Pampas Biome of South
      America, with descriptions of new Rhinoleucophenga species.
AB  - In the last three decades some faunal surveys of Drosophilidae have been done in
      several environments in the Neotropical region, especially in Brazil. But
      approximately 30 to 50% of the drosophilids in Brazil have not yet been
      described, and the degradation of some biomes causes a profound loss of species
      diversity, as well as the loss of information about the present structureof their
      communities. This is the situation with the pampas biome, which covers
      southernmost Brazil, all of Uruguay, and the central region of eastern Argentina.
      For the present study, seasonal collections were made in a natural area of pampas
      within the limits of the municipality of Bossoroca in the state of Rio Grande do
      Sul, Brazil (28 degrees 45'01"S 54 degrees 56'55"W), from April 2011 to April
      2012. A total of 7,164 drosophilids of 51 species were collected, comprising 36
      species belonging to Drosophila Fallen, ten of Rhinoleucophenga Hendel, two of
      Amiota Loew, two of Zygothrica Wiedemann and one of Zaprionus Coquillett. Some
      species were recorded for the first time in pampas: Drosophila briegeri Pavan &
      Breuer, D. fuscolineata Duda, Rhinoleucophenga obesa (Loew), R. punctulata Duda,
      R. subradiata Duda and Zygothrica orbitalis (Sturtevant). Furthermore, three new
      species of genus Rhinoleucophenga were described: R. pampeana sp. nov., R.
      missionera sp. nov. and R. sulina sp. nov. A dichotomous key is given for the
      Rhinoleucophenga species recorded in pampas. An intensive literature search is
      reviewed of drosophilid species recorded in pampas of Brazil, Uruguay and
      Argentina, including taxonomic, genetic, evolutionary, and ecological studies.
      Despite Brazilian pampas being the richest when compared with Uruguay and
      Argentina, the three countries presented the same problem: huge areas with a
      barely surveyed Drosophilidae fauna. The combination of this information and the
      knowledge of the current state of preservation of pampas stress the necessity and
      importance of creating new conservation areas to preserve the natural
      biodiversity of pampas.

PMID- 24871723
TI  - Diversity of Indo-West Pacific Siphonaria (Mollusca: Gastropoda: Euthyneura).
AB  - Species of the limpet genus Siphonaria (Gastropoda: Euthyneura) are commonly
      found in the rocky intertidal, worldwide, except in the Arctic. In total, 205
      species-group names are available and not permanently invalid. However,
      estimating the actual species diversity of Siphonaria has remained challenging,
      mainly because past authors have interpreted differently the variation of shell
      characters, resulting in different taxonomic accounts. Species diversity of
      Siphonaria is evaluated for the first time here based on DNA sequence data (three
      mitochondrial gene fragments: COI, 12S, and 16S) and a large sampling focusing on
      the tropical and subtropical Indo-West Pacific (from eastern Africa to Hawaii):
      new sequences are provided for 153 individuals, 123 of which were collected from
      93 locations throughout the Indo-West Pacific. In total, 41 species (molecular
      units) are recognized worldwide (31 from the Indo-West Pacific), all of which are
      strongly supported. Potential names are discussed for those 41 species, based on
      traditional taxonomy. The shells of 66 of the individuals from which DNA was
      extracted are illustrated: intra- and inter-specific variation is documented in
      detail and discussed in the light of new molecular results. It is shown that many
      species could hardly be identified based on the shell only, because the variation
      of shell characters is too high and overlaps between species. Geographically, no
      species is found across the entire Indo-West Pacific, where quite a few species
      seem to be endemic to restricted areas. The biogeography of Siphonaria in the
      Indo-West Pacific is compared to other groups. 

PMID- 24871724
TI  - Perlidae (plecoptera) from southeastern Santa Catarina State, southern Brazil.
AB  - Seven species of Perlidae (Plecoptera) from southeastern Santa Catarina State,
      (Brazil) were studied: Anacroneuria fiorentini De Ribeiro & Froehlich, A. ofaye
      Froehlich, A. trimacula Jewett, Kempnyia mirim Froehlich, K. neotropica (Jacobson
      & Bianchi), and K. tenebrosa Klapalek. A new species, A. xokleng is also
      described.   

PMID- 24871725
TI  - A new troglobitic species of Coarazuphium Gnaspini, Vanin & Godoy (Coleoptera,
      Carabidae, Zuphiini) from a cave in Parana State, Southern Brazil.
AB  - A new troglobitic species of the Zuphiini genus Coarazuphium, C. ricardoi new
      species, is described on the basis of specimens collected inside the "Gruta do
      Varzeao" cave, in Parana State. This is the first species of Coarazuphium
      described from Southern Brazil. The new species is compared with three other
      troglobitic species of the genus that are microphthalmous and have the elytral
      apical margins truncate (C. pains Alvares & Ferreira, C. tapiguassu Pellegrini &
      Ferreira and C. whiteheadi Ball & Shpeley). The most recent published keys for
      species identification of Coarazuphium are updated to include the new species. 

PMID- 24871726
TI  - Relicts of a forested past: Southernmost distribution of the hairy frog genus
      Trichobatrachus Boulenger, 1900 (Anura: Arthroleptidae) in the Serra do Pingano
      region of Angola with comments on its taxonomic status.
AB  - The monotypic genus Trichobatrachus, with its sole representative, the hairy
      frog, Trichobatrachus robustus Boulenger, 1900, could be considered one of the
      most well-known frogs of Africa. Despite its broad recognition and the fact that
      it is considered wide-spread and locally common (Amiet & Burger 2004),
      surprisingly little is known about the actual distribution and the specific
      occurrence patterns of the species. It was originally described by Boulenger
      (1900) from the Benito River, previously erroneously stated to be located in
      Gabon. However, Lotters et al. (2001) clarified that the type locality was
      actually situated in Equatorial Guinea, then part of French Congo, and
      subsequently provided the first confirmed country record for Gabon. Hairy frogs
      were previously included in the herpetofaunal lists of Cameroon (Parker 1936;
      Perret & Mertens 1957), the Democratic Republic of Congo (Laurent 1956), and
      Nigeria (Schiotz 1963). More recently published accounts list them for Cameroon
      (Euskirchen et al. 1999; Herrmann et al. 2005; Gonwouo & Rodel 2008), Equatorial
      Guinea (De la Riva 1994; Lasso et al. 2002), Gabon (Lotters et al. 2001; Rodel &
      Pauwels 2003; Burger et al. 2004; Pauwels & Rodel 2007; Bell et al. 2011), and
      the Democratic Republic of Congo (DRC, Fretey et al. 2011), and speculate about
      their potential occurrence in Congo and the Cabinda enclave of Angola (Amiet &
      Burger 2004). The DRC record so far represented the most southerly distribution,
      while the most northerly account comes from the Adamaoua Province of northern
      Cameroon (Tadpole voucher MHNG-AMP/ERPI-1035.006 from Benoue source, Northern
      cliff Ngaoundere, Adamaoua, Cameroon/Adamaoua Province, cf. Perret 1966).
      Specimens stored in the collection at the Royal Museum of Central Africa,
      Tervuren (RMCA) under collection numbers RMCA B 90060.0004-11 confirm the
      occurrence of the species in Congo. To our knowledge, these specimens represent
      yet unpublished first country records.

PMID- 24871727
TI  - The Australian Monstrilloida (Crustacea: Copepoda) I. Monstrillopsis Sars,
      Maemonstrilla Grygier & Ohtsuka, and Australomonstrillopsis gen. nov.
AB  - Monstrilloid copepods were collected during zooplankton surveys in reef and
      coastal areas of Australia. Representatives of all four genera of the
      Monstrilloida (Monstrilla Dana, Monstrillopsis Sars, Cymbasoma Thompson, and
      Maemonstrilla Grygier & Ohtsuka) were recorded. In this contribution a taxonomic
      analysis of specimens belonging to the latter two genera is provided, and a new
      genus described. The genus Monstrillopsis was represented exclusively by male
      specimens, on the basis of which three new species are described: Mon. hastata
      sp. nov., Mon. boonwurrungorum sp. nov., and Mon. nanus sp. nov. These are
      distinguished from each other and previously described species of this genus by
      details of the genital complex (or genital apparatus), body size, ornamentation
      of the cephalic surface, number of caudal setae, and characteristic modifications
      of the fifth antennular segment. All have distinctive characters not associated
      with sexual modifications, which will ease the task of matching females collected
      in future studies. Australomonstrillopsis gen. nov. is proposed to accommodate a
      male specimen with a unique combination of characters including massively
      developed caudal rami, cephalic perioral protuberances, and absence of an inner
      seta on the first exopodal segment of legs 1-4, among other characters. The new
      genus is monotypic and contains A. crassicaudata sp. nov. Three of the four new
      species of Maemonstrilla (Mae. ohtsukai sp. nov., Mae. hoi sp. nov., and Mae.
      protuberans sp. nov.) belong to the Mae. hyottoko species group, and the
      remaining one, Mae. crenulata sp. nov., belongs to the Mae. turgida group. Each
      of the new species of Maemonstrilla from Australia can be distinguished from its
      known congeners by a unique combination of characters including the type of body
      reticulation, body size, antennule and body proportions, distinctive characters
      of the swimming legs, details of the antennular armature, and the
      presence/absence of a posteroventral process on the genital compound somite. With
      the addition of the four new species of Monstrillopsis and the four of
      Maemonstrilla described herein, the number of species in these genera has
      increased to 13 and 11 species, respectively. In no case did congeneric species
      co-occur, hinting that there may be a rich species diversity yet to be discovered
      within the Australian Monstrilloida. 

PMID- 24871728
TI  - A revision of the spirit loaches, genus Lepidocephalus (Cypriniformes,
      Cobitidae).
AB  - Lepidocephalus has been assumed to include only two species and confined to
      peninsular Malaysia and Indonesia. However, based on records and collections
      reported herein, the genus contains five species and is most common in the Chao
      Phraya basin of Thailand. Large rivers seem to be the preferred habitat, and
      difficulty in collecting these rivers may account for the paucity of specimens in
      collections. The known range of these five species includes western and southern
      Borneo, Java, Sumatra, peninsular Malaysia, and central Thailand. 

PMID- 24871729
TI  - Neotropical species of Meteorus Haliday (Hymenoptera: Braconidae: Meteorinae)
      parasitizing Arctiinae (Lepidoptera: Noctuoidea: Erebidae).
AB  - Three new species of Meteorus parasitoids of Arctiinae are described: Meteorus
      anuae n. sp., M. juliae n. sp. and M. mirandae n. sp. The first biological record
      for M. cecavorum Aguirre & Shaw as well as its cocoon description is reported. A
      comprehensive key for the Neotropical Meteorus attacking Arctiinae is provided. A
      total of nine Meteorus species have been reared from Arctiinae in the Neotropical
      Region. Six of them are gregarious and three solitary. The biological information
      about host and food plants concurs with the hypothesis of specialist parasitoids
      preferring "nasty" caterpillars.

PMID- 24871731
TI  - Review of the Olethreutes bowmanana-magadana species group, with the description
      of a new species from the Amur River, Russia (Lepidoptera, Tortricidae).
AB  - We define and review the Olethreutes bowmanana-magadana species group comprised
      of Olethreutes bowmanana (McDunnough), O. magadana (Falkovitsh), O. kamtshadala
      (Falkovitsh), and O. pivanica, sp. n., the last from petrophytous sunny slopes in
      the Amur River. The new species differs from other species of the group by a
      narrow, triangular-shaped apical process from the sacculus; a round, wide, apical
      bulb from the cucullus; and a longer, narrow neck of the valva. 

PMID- 24871730
TI  - The first description of the male Euophrys atrata and E. bulbus from southern
      China (Araneae: Salticidae).
AB  - The males of Euophrys atrata Song & Chai,1992 and Euophrys bulbus Bao & Peng,
      2002 are described and illustrated for the first time from southern China. 

PMID- 24871732
TI  - Caecilita Wake & Donnelly, 2010 (Amphibia: Gymnophiona) is not lungless:
      implications for taxonomy and for understanding the evolution of lunglessness .
AB  - According to current understanding, five lineages of amphibians, but no other
      tetrapods, are secondarily lungless and are believed to rely exclusively on
      cutaneous gas exchange. One explanation of the evolutionary loss of lungs
      interprets lunglessness as an adaptation to reduce buoyancy in fast-flowing
      aquatic environments, reasoning that excessive buoyancy in such an environment
      would cause organisms being swept away. While not uncontroversial, this
      hypothesis provides a plausible potential explanation of the evolution of
      lunglessness in four of the five lungless amphibian lineages. The exception is
      the most recently reported lungless lineage, the newly described Guyanan
      caecilian genus and species Caecilita iwokramae Wake & Donnelly, 2010, which is
      inconsistent with the reduced disadvantageous buoyancy hypothesis by virtue of it
      seemingly being terrestrial and having a terrestrial ancestry. Re-examination of
      the previously only known specimen of C. iwokramae and of recently collected
      additional material reveal that this species possesses a reasonably well
      developed right lung and is a species of the pre-existing caecilian genus
      Microcaecilia Taylor, 1968. We therefore place Caecilita in the synonymy of
      Microcaecilia, and re-evaluate the plausibility of the reduced disadvantageous
      buoyancy hypothesis as a general explanation of the evolution of lunglessness. 

PMID- 24871733
TI  - Description of Atrocalopteryx fasciata spec. nov. from Yunnan, China (Odonata:
      Calopterygidae).
AB  - Atrocalopteryx fasciata Yang, Hamalainen & Zhang, spec. nov. (holotype ?, from
      China, Yunnan, Dehong, Yingjiang, deposited at Odonata Collection of College of
      Agriculture and Life Sciences, Dali University, Dali, Yunnan, China) is described
      and illustrated from the male sex. It is compared with Atrocalopteryx laosica
      (Fraser, 1933). 

PMID- 24871734
TI  - On the identity of Ypsolopha lonicerella Stockl, 1922 (Lepidoptera,
      Ypsolophidae).
AB  - Ypsolopha lonicerella Stockl, 1922 is shown to be a junior synonym of Y.
      leuconotella Snellen, 1884. 

PMID- 24871735
TI  - The correct authorship and type locality of Melanocorypha leucoptera (Aves:
      Passeriformes, Alaudidae).

PMID- 24871736
TI  - Inundicola Bravo, Isler, and Brumfield 2013 is a junior synonym of Akletos
      Dunajewski 1948 (Aves: Passeriformes: Thamnophilidae).

PMID- 24871737
TI  - The genus Amnestus Dallas (Hemiptera: Heteroptera: Cydnidae: Amnestinae) in
      Mexico, with the description of eleven new species from Chiapas.
AB  - The genus Amnestus is one of the most diverse genera of burrowing bugs. In recent
      years it has been possible to obtain great quantities of specimens, including
      some new species, due to collecting in special habitats and using different
      trapping techniques. In this paper we describe eleven new species for the state
      of Chiapas, Mexico. Full descriptions, illustrations of dorsal habitus, fore and
      hind legs, prosternal carina, external scent efferent system, and paramere of the
      new species: A. carinopilosus, A. chiapensis, A. cristobalensis, A. denticulatus,
      A. laevifemoralis, A. longinoi, A. lorenae, A. marcelae, A. puncticarinatus, A.
      santiagensis, A. septemclavatus, are included. Amnestus bergrothi and Amnestus
      stali are redescribed, also illustrated, and lectotypes assigned, because they
      were originally described based on females. The original description of Amnestus
      dallasi is also included, because it was described based on one female and it is
      the only specimen known. Brief descriptions of the other 14 Mexican known species
      and their distribution are also included. A key and a general discussion to
      separate the 28 Mexican species are also provided. 

PMID- 24871738
TI  - First report of geophilid centipedes of the genus Ribautia (Myriapoda: Chilopoda:
      Geophilomorpha) from the Atlantic Forest biome, with description of a new
      miniature species from Misiones Province, Northeastern Argentina.
AB  - Ribautia paranaensis sp. nov. a new miniature species of geophilid centipede from
      the Upper Parana Atlantic Forest (the westernmost of the fifteen ecoregions
      comprising the Atlantic Forest biome sensu Di Bitetti et al. 2003), is herein
      described and illustrated. The new species is characterized by having the coxal
      organs grouped in clusters (one of these in each coxopleuron of the ultimate leg
      bearing segment) and a claw-like pretarsus in the ultimate legs; these traits
      being shared by three other Neotropical members of the genus, i.e., R. combinata
      Pereira, Uliana & Minelli, 2006 (from the Amazonian rainforest of Peru), R.
      jakulicai Pereira, 2007 (from the Yungas rainforest of Northwestern Argentina),
      and R. lewisi Pereira, 2013 (collected in a gallery forest in the Mesopotamian
      region, Northeastern Argentina). R. paranaensis sp. nov. represents the first
      report of Ribautia Brolemann, 1909 in the entire Atlantic Forest biome, and the
      third confirmed record of the taxon from Argentina. 

PMID- 24871739
TI  - Dachtylembia, a new genus in the family Teratembiidae (Embioptera) from Thailand.
AB  - Dachtylembia gen. nov. (Embioptera: Teratembiidae), is described and illustrated
      based on specimens of a new species (D. siamensis) collected from Thailand. The
      geographical distribution of this species in Thailand is mapped. 

PMID- 24871740
TI  - A revision of the types of Neotropical Porricondylinae (Diptera: Cecidomyiidae) .
AB  - The type material of six species of Porricondylinae (Diptera: Cecidomyiidae)
      described from the Neotropical Region between 1905 and 1936 is re-examined. On
      the basis of revised adult descriptions the classification of these species is
      analyzed and discussed. Lectotypes are designated for Asynapta citrinae Felt, A.
      mangiferae Felt, Holoneurus occidentalis Felt, and Porricondyla gossypii
      Coquillett. 

PMID- 24871741
TI  - First occurrence of Beroe forskalii (Ctenophora) in South American Atlantic
      coastal waters, with notes on the use of macrociliary patterns for beroid
      identification.
AB  - Beroe forskalii Milne Edwards, 1841 is an oceanic ctenophore with a global
      distribution. The present study provides the first record of Beroe forskalii for
      the South American Atlantic coast, including a redescription of the species and a
      discussion on the utility of macrociliary patterns for the correct identification
      of at least some beroid species, exemplified by a comparison of the macrociliary
      patterns of Beroe forskalii and Beroe ovata (Chamisso & Eysenhardt, 1821). 

PMID- 24871742
TI  - Swedish Plectida (Nematoda). Part 5. Rhadinema timmi (Vitiello, 1971) comb. n.
AB  - Leptolaimus timmi Vitiello, 1971 is redescribed from bottom sediments collected
      in the Skagerrak off the west coast of Sweden. New morphological data necessitate
      the transfer of this species to the genus Rhadinema Cobb, 1920. The main
      diagnostic characters of Rhadinema timmi (Vitiello, 1971) comb. n. include: 1.3
      1.8 mm long body; rounded labial region weakly offset from body contour; cephalic
      setae 2-4 um long; amphid located 12-19 um from anterior end; first body pore
      located 22-30 um from anterior end; lateral field absent; stoma tubular:
      cheilostom with six weakly cuticularised longitudinal rugae, gymnostom with
      sclerotized bar-shaped rhabdia, stegostom long, tubular; female without
      supplements, vagina without pars refringens, vulva midventral; male with 10-11
      tubular and without alveolar supplements; spicules arcuate and 21-30 um long. 

PMID- 24871743
TI  - Two new species of Blaberidae (Blattaria) collected in the Santa Lucia Station,
      Espirito Santo State, Brazil.
AB  - This contribution presents two new species belonging to the genera Audreia
      (Shelford, 1910) and Epilampra Burmeister, 1838, subfamily Epilamprinae
      (Blattaria, Blaberidae). The Blaberidae include large and medium-bodied species
      with a high adaptive capacity. The new taxa were collected in Espirito Santo
      State and evaluated based on the analysis of subgenital and supranal plates and
      genital parts, by means of standard dissection techniques, by comparison with
      specimens of the corresponding genera deposited in the collection of the Museu
      Nacional and with published descriptions. 

PMID- 24871744
TI  - Eutheia bekchievi sp. n. (Coleoptera, Staphylinidae, Scydmaeninae) from Bulgaria.

PMID- 24871745
TI  - The tadpole of the Swelled Vent Frog Feirana quadranus (Anura: Ranidae): oral,
      chondrocranial and hyobranchial morphology.

PMID- 24871746
TI  - On the genus Hydrometra Latreille (Hemiptera: Heteroptera: Hydrometridae) from
      India with description of two new species .
AB  - Two new species of the genus Hydrometra Latreille, 1796, are described from the
      Oriental Region. Hydrometra cherukolensis sp. nov. is described from Kanyakumari
      District, Tamil Nadu, India, belongs to the Hydrometra julieni species group, and
      is closely related to H. julieni Hungerford & Evans, 1934 and H. julienoidea
      Polhemus & Polhemus, 1995. Hydrometra nicobarensis sp. nov. is described from the
      Great Nicobar Biosphere Reserve (GNBR), Andaman and Nicobar Islands, India,
      belongs to the Hydrometra lineata species group and this new species is closely
      related to H. borneensis Zettel & Yang, 2004. Hydrometra okinawana Drake, 1951,
      collected from GNBR, Andaman and Nicobar Islands, and is the first record for
      India. Hydrometra butleri Hungerford & Evans, 1934, is redescribed and notes on
      H. greeni Kirkaldy, 1898 are given. All together five species of Hydrometra, H.
      butleri, H. cherukolensis sp. nov., H. greeni, H. nicobarensis sp. nov. and H.
      okinawana are reported in the present study from India. A key to the species of
      Hydrometra of India and the distribution maps are also provided. 

PMID- 24871747
TI  - Review of the genus Susuacanga (Coleoptera, Cerambycidae, Cerambycinae).
AB  - The genus Susuacanga Martins, 1997 is redescribed. A new combination, S.
      blancaneaui (Bates, 1880) comb. nov. and a new synonymy, Eburia unicolor Bates,
      1870 = S. octoguttata (Germar, 1821) are proposed. The genus is now composed of
      12 species. The geographical distribution of S. opaca is expanded to include
      Belize. Photographs of Susuacanga species are included and a key to differentiate
      them is provided. 

PMID- 24871748
TI  - Six new species of the Platypalpus pallidiventris-cursitans group (Diptera:
      Hybotidae) from the Caucasus.
AB  - Six new species of the genus Platypalpus are described from the Caucasus: P.
      abagoensis sp. nov. (Russia: Republic of Adygea), P. arzanovi sp. nov. (Russia:
      Krasnodarskiy Territory, Rostov Prov.), P. gazaryani sp. nov. (Russia: Republic
      of Adygea), P. kamyshanovensis sp. nov. (Russia: Krasnodarskiy Territory), P.
      odintsovi sp. nov. (Russia: Krasnodarskiy Territory), P. neberdzaensis sp. nov.
      (Russia: Krasnodarskiy Territory). 

PMID- 24871749
TI  - Intrageneric phylogenetics based on mitochondrial DNA variation among fifteen
      harpactorine assassin bugs with four ecotypes and three morphs (Hemiptera:
      Reduviidae: Harpactorinae).
AB  - Available mitochondrial DNA sequences viz., 16S, Cyt b, Cyt c oxidase subunit -
      I, and Cyt c subunit-like - I gene of Rhynocoris (Kolenati) species were
      subjected to phylogenetic analysis to understand the intrageneric and
      intraspecific variations and the role of geographical isolation on speciation;
      using CLUSTAL W in MEGA version 5.1. This analysis includes fifteen species and
      four ecotypes of R. kumarii Ambrose and Livingstone and three morphs of R.
      marginatus (Fabricius) from four countries viz., Canada, China, Korea, and South
      Africa. The pairwise genetic distances were calculated and phylograms were
      constructed using Maximum Likelihood, Maximum Parsimony, and Neighbor-Joining
      methods. These preliminary analyses not only demarcated the fifteen species of
      Rhynocoris, the four ecotypes of R. kumarii, and the three morphs of R.
      marginatus, but also revealed phylogenetic relationships and the role of
      geographical isolation and polymorphism on speciation. 

PMID- 24871750
TI  - Two new species of Phyllodistomum Braun, 1899 (Trematoda: Gorgoderidae Looss,
      1899) from Great Barrier Reef fishes.
AB  - Two new species of Phyllodistomum Braun, 1899 are described from the urinary
      bladder of fishes of the Great Barrier Reef. Phyllodistomum hoggettae n. sp. is
      described from Plectropomus leopardus (leopard coralgrouper) (Serranidae) and P.
      vaili n. sp. is described from Mulloidichthys vanicolensis (yellowfin goatfish)
      and M. flavolineatus (yellowstripe goatfish) (Mullidae). These species are
      compared with 26 previously described marine Phyllodistomum species and found to
      be distinct in combinations of body shape, sucker ratio and shape of the gonads.
      Preliminary molecular data also demonstrate that they are distinct from each
      other and for those other species for which data are available. 

PMID- 24871751
TI  - A new species of Luchoelmis Spangler & Staines (Coleoptera: Elmidae) from
      Argentina and its probable larva.
AB  - A new species of riffle beetle from southwestern Argentina, Luchoelmis
      kapenkemkensis, is described. Its diagnostic characters are illustrated and the
      key for the identification the species of the genus is updated. A larva, very
      likely belonging to this species, is also described and compared to other related
      larvae. 

PMID- 24871752
TI  - A taxonomic synopsis of Limnogeton Mayr, 1853 (Insecta: Hemiptera: Heteroptera:
      Belostomatidae).
AB  - The Afrotropical Belostomatidae fauna has long proved to be a difficult taxonomic
      problem, not so much for the overwhelmingly large number of species involved but
      rather because of a lack of trained specialists. The rarity of some taxa also
      contributes to confusion, because some species remain poorly described or are
      known only from one or two specimens. During a visit to the Museum National
      d'Histoire Naturelle, Paris, France and the Musee Royal de l'Afrique Centrale,
      Tervuren, Belgium, it was possible to comprehensively review the Limnogeton
      species based mainly on the specimens housed in the aforementioned collections.
      An updated key to adults of all species presently included in the genus,
      particularly based on male genitalia characters studied during the present study,
      has been provided. 

PMID- 24871753
TI  - Two new species of the genus Callicera Panzer (Diptera: Syrphidae) from the
      Palaearctic Region.
AB  - Two new species of the genus Callicera Panzer are described from the Palaearctic
      region: C. exigua sp. nov. from the Russian Altay and C. scintilla sp. nov. from
      Jordan. A key is provided for all Callicera species of the Palaearctic Region. 

PMID- 24871754
TI  - Two new species and a new record of Anacroneuria (Plecoptera: Perlidae) from
      Central Brazil.
AB  - We studied specimens of Anacroneuria (Plecoptera: Perlidae) collected from the
      region of Goias City, Goias State, Brazil. Two new species of Anacroneuria, A.
      meloi Bispo & Novaes and A. corae Bispo & Novaes are described and A. debilis
      (Pictet) is recorded for the first time from Goias State. 

PMID- 24871755
TI  - Nirvanguina Zhang & Webb (Hemiptera: Cicadellidae: Deltocephalinae), a new record
      for China, with description of a new species.
AB  - The previously monotypic leafhopper genus Nirvanguina Zhang & Webb
      (Deltocephalinae, Drabescini, Paraboloponina), recorded from Australia and New
      Guinea, is recorded from mainland Asia (China) for the first time and a new
      species, N. pectena sp. nov., from Fanjingshan Mountain in Guizhou Prov., China,
      is described and illustrated.

PMID- 24871756
TI  - New Delhi Metallo-beta-lactamase around the world: an eReview using Google Maps.
AB  - Gram-negative carbapenem-resistant bacteria, in particular those producing New
      Delhi Metallo-betalactamase-1 (NDM-1), are a major global health problem. To
      inform the scientific and medical community in real time about worldwide
      dissemination of isolates of NDM-1-producing bacteria, we used the PubMed
      database to review all available publications from the first description in 2009
      up to 31 December 2012, and created a regularly updated worldwide dissemination
      map using a web-based mapping application. We retrieved 33 reviews, and 136 case
      reports describing 950 isolates of NDM-1-producing bacteria. Klebsiella
      pneumoniae (n= 359) and Escherichia coli (n=268) were the most commonly reported
      bacteria producing NDM-1 enzyme. Several case reports of infections due to
      imported NDM-1 producing bacteria have been reported in a number of countries,
      including the United Kingdom, Italy, and Oman. In most cases (132/153, 86.3%),
      patients had connections with the Indian subcontinent or Balkan countries. Those
      infected were originally from these areas, had either spent time and/or been
      hospitalised there, or were potentially linked to other patients who had been
      hospitalised in these regions. By using Google Maps, we were able to trace spread
      of NDM-1-producing bacteria. We strongly encourage epidemiologists to use these
      types of interactive tools for surveillance purposes and use the information to
      prevent the spread and outbreaks of such bacteria.

PMID- 24871757
TI  - Rotavirus vaccination coverage and adherence to recommended age among infants in
      Flanders (Belgium) in 2012.
AB  - In Belgium, rotavirus vaccination has been recommended and partially reimbursed
      since October 2006. Through a retrospective survey in 2012, we estimated the
      coverage rate of the rotavirus vaccination in Flanders among infants born in
      2010. Using a standardised questionnaire, 874 families were interviewed at home,
      collecting information on demographic characteristics, socio-economic background
      and documented vaccination history (updated from medical files and vaccination
      database, if needed). Adherence to the recommended age for vaccination (8, 12 and
      16 weeks) was also assessed. The coverage rate for two doses of rotavirus
      vaccination was 92.2% (95% confidence interval: 90.2-93.8). Respectively 31.7%
      and 10.1% of the children received their first and second dose at the recommended
      age. Incomplete vaccination was often a deliberate choice of the parents. Only
      eight children (1%) were vaccinated after the maximum age of 26 weeks. Factors
      identified by multiple logistic regression as related to incomplete vaccination
      were: living in the province of Antwerp, unemployed mother, and three or more
      older siblings in the household. Four years after introduction, the coverage
      rates were surprisingly high for a vaccine that is not fully reimbursed and not
      readily available in the vaccinator's fridge, which is the case for the other
      recommended infant vaccines.

PMID- 24871758
TI  - A low-cost, sustainable, second generation system for surveillance of people
      living with HIV in Spain: 10-year trends in behavioural and clinical indicators,
      2002 to 2011.
AB  - A second-generation surveillance system of people infected with human
      immunodeficiency virus (HIV) has been implemented in Spain. Behavioural and
      clinical data were collected between 2002 and 2011 through an annual one-day,
      cross-sectional survey in public hospitals, including all in- and outpatients
      receiving HIVrelated care on the survey day. Mean age increased over time (from
      38.7 years in 2002 to 43.8 years in 2011) and 68.4% of the 7,205 subjects were
      male. The proportion of migrants increased from 6.1% to 15.9%, while people who
      inject or used to inject drugs (PWID and Ex-PWID) decreased and men who have sex
      with men (MSM) and heterosexuals increased. Unprotected intercourse at last sex
      increased among MSM and PWID/Ex-PWID. Patients receiving antiretroviral treatment
      increased significantly from 76.0% to 88.2% as did those with CD4 T-cell counts
      >=350 (from 48.2% to 66.9%) and viral copies <200 (from 47.0% to 85.2%). HIV
      infected people with hepatitis C virus RNA decreased from 36.0% in 2004 to 29.9%
      in 2011, while those with HBsAg remained stable at around 4.4%. Implementation of
      a low-cost, sustainable system for second-generation surveillance in people
      living with HIV is feasible. In Spain, the information obtained has helped to
      define and refine public health policy and document treatment effectiveness.

PMID- 24871759
TI  - Letter to the Editor: Middle East respiratory syndrome coronavirus (MERS-CoV) in
      dromedary camels: are dromedary camels a reservoir for MERS-CoV?

PMID- 24871760
TI  - Authors reply: Middle East respiratory syndrome coronavirus (MERS-CoV) in
      dromedary camels: are dromedary camels a reservoir for MERS-CoV?

PMID- 24871761
TI  - Letter to the Editor: smoking and older age associated with mumps in an outbreak
      in a group of highly-vaccinated individuals attending a youth club party, The
      Netherlands, 2012.

PMID- 24871764
TI  - Aneurysm pressure measurement before and after placement of a Pipeline stent:
      feasibility study using a 0.014 inch pressure wire for coronary intervention.
AB  - Flow-diverting stents have provided a new endovascular capacity to reconstruct an
      intracranial aneurysm with its diseased parent artery. The results of first
      generation flow diversion stents have been encouraging, with even large or giant
      treated aneurysms achieving complete angiographic occlusion at 12-month follow
      up. Numerous clinical reports have described a slow progressive thrombosis
      pattern and gradual increase in rate of complete aneurysm obliteration over time.
      Despite promising early results, some complications specific to flow-diverting
      stents have been encountered. Chief among them is delayed aneurysm rupture. This
      complication did not emerge with stent-assisted coil embolization of intracranial
      aneurysms, and the underlying cause has not been established. However, new
      evidence suggests that persistent, or even increased, aneurysm pressure after
      stent placement may play a role in some delayed ruptures. We sought to evaluate
      this phenomenon by measuring intrasaccular pressure before and after stent
      placement using two different 0.014 inch coronary pressure measurement wires. Two
      patients with giant internal carotid artery aneurysms treated with flow-diverting
      stents were evaluated. Before and after stent deployment, intrasaccular aneurysm
      and systemic arterial pressures were recorded for 60 s and compared. In both
      cases, intrasaccular pressure measurement with the use of 0.014 inch pressure
      wire system was feasible; the pressure wires could be pushed out of the
      microcatheter placed in the aneurysms without friction or unexpected
      microcatheter motion. Despite successful flow-diverting stent deployment and
      angiographic flow diversion effects with excellent wall opposition across the
      aneurysm necks, there was no significant difference between intrasaccular and
      systemic pressures. 

PMID- 24871763
TI  - Purification and characterization of an extracellular, thermo-alkali-stable,
      metal tolerant laccase from Bacillus tequilensis SN4.
AB  - A novel extracellular thermo-alkali-stable laccase from Bacillus tequilensis SN4
      (SN4LAC) was purified to homogeneity. The laccase was a monomeric protein of
      molecular weight 32 KDa. UV-visible spectrum and peptide mass fingerprinting
      results showed that SN4LAC is a multicopper oxidase. Laccase was active in broad
      range of phenolic and non-phenolic substrates. Catalytic efficiency (kcat/Km)
      showed that 2, 6-dimethoxyphenol was most efficiently oxidized by the enzyme. The
      enzyme was inhibited by conventional inhibitors of laccase like sodium azide,
      cysteine, dithiothreitol and beta-mercaptoethanol. SN4LAC was found to be highly
      thermostable, having temperature optimum at 85 degrees C and could retain more
      than 80% activity at 70 degrees C for 24 h. The optimum pH of activity for 2, 6
      dimethoxyphenol, 2, 2'-azino bis[3-ethylbenzthiazoline-6-sulfonate],
      syringaldazine and guaiacol was 8.0, 5.5, 6.5 and 8.0 respectively. Enzyme was
      alkali-stable as it retained more than 75% activity at pH 9.0 for 24 h. Activity
      of the enzyme was significantly enhanced by Cu2+, Co2+, SDS and CTAB, while it
      was stable in the presence of halides, most of the other metal ions and
      surfactants. The extracellular nature and stability of SN4LAC in extreme
      conditions such as high temperature, pH, heavy metals, halides and detergents
      makes it a highly suitable candidate for biotechnological and industrial
      applications. 

PMID- 24871765
TI  - System dynamics approach for modeling of sugar beet yield considering the effects
      of climatic variables.
AB  - BACKGROUND: The aim of this study was to develop a system dynamics model for
      computation of yields and to investigate the dependency of yields on some major
      climatic parameters, i.e. temperature and rainfall, for Beta vulgaris subsp.
      (sugar beet crops) under future climate change scenarios. RESULTS: A system
      dynamics model was developed which takes account of the effects of rainfall and
      temperature on sugar beet yields under limited irrigation conditions. A
      relationship was also developed between the seasonal evapotranspiration and
      seasonal growing degree days for sugar beet crops. The proposed model was set to
      run for the present time period of 1993-2012 and for the future period 2013-2040
      for Lethbridge region (Alberta, Canada). The model provides sugar beet yields on
      a yearly basis which are comparable to the present field data. It was found that
      the future average yield will be increased at about 14% with respect to the
      present average yield. CONCLUSION: The proposed model can help to improve the
      understanding of soil water conditions and irrigation water requirements of an
      area under certain climatic conditions and can be used for future prediction of
      yields for any crops in any region (with the required information to be
      provided). The developed system dynamics model can be used as a supporting tool
      for decision making, for improvement of agricultural management practice of any
      region.

PMID- 24871766
TI  - Fluorinated lamellar phases: structural characterisation and use as templates for
      highly ordered silica materials.
AB  - Highly ordered silica was synthesised by using a lamellar phase comprising the
      anionic fluorinated surfactant sodium perfluorooctanoate and the partially
      fluorinated co-surfactant/oil 1H,1H,2H,2H-perfluorooctan-1-ol in water. The phase
      behaviour of this system was thoroughly analysed, and it was found that even low
      levels of the alcohol (<0.5 mol%) were sufficient to induce a phase change from
      normal micelles to a lamellar phase, rationalised as a result of geometric and
      electrostatic effects. The properties of these phases were compared to their
      hydrocarbon analogues, demonstrating the unique and valuable properties exhibited
      by fluorocarbons, directly related with the observed nanostructure. Small-angle
      neutron scattering was used to analyse the internal structure of the systems,
      providing information on the inter-lamellar spacing, bilayer thickness and
      membrane elasticity. The potential for these phases to act as shear-thinning
      lubricants was assessed using oscillatory rheology, obtaining shear-dependent
      viscosity along with storage and loss moduli. 

PMID- 24871767
TI  - Equiatomic ternary chalcogenide: PdPS and its reduced graphene oxide composite
      for efficient electrocatalytic hydrogen evolution.
AB  - The layered ternary chalcogenide, palladium phosphorous sulphide (PdPS), and its
      composite with reduced graphene oxide are shown to be efficient hydrogen
      evolution electrocatalysts. The Tafel slope and the exchange current density
      values associated with hydrogen evolution reaction are determined to be 46 mV
      dec(-1) and 1.4 * 10(-4) A cm(-2) respectively. 

PMID- 24871769
TI  - The integrated behavioral health service delivery system model.
AB  - Costs and effective management of health care in general, and behavioral health
      care in particular, have been of primary importance and concern to federal,
      state, and local governments. With the passage of Health Care Reform (HCR) these
      concerns will only escalate. Thus, the necessity for the development of
      innovative, successful, and integrated cost-effective treatments and procedures
      is evident. The behavioral health care model presented here is proposed to
      address these needs. The model centers on the composition of effective
      psychosocial treatment and provides a cost analysis of social work and its
      services. By defining the problems that need to be addressed in health care
      management and cost containment, and applying findings of evidence-based studies,
      this article provides an effective model for health care organizations. It also
      presents a profile of the behavioral health social worker, defining the requisite
      abilities for effectiveness in the role and looking at the key impact areas for a
      behavioral health model. This comprehensive guide will prepare new social workers
      entering health care organizations as well as provide a valuable reference for
      existing social workers, academics, and practitioners of behavioral health care.

PMID- 24871770
TI  - Investigating health disparities through community-based participatory research:
      lessons learned from a process evaluation.
AB  - This article describes one university's efforts to partner with a local agency
      (the "Coalition") within a disadvantaged, predominantly African American
      neighborhood, to assist them with studying their community's health disparities
      and health care access. The final, mutually agreed-upon plan used a community
      based participatory research approach, wherein university researchers prepared
      neighborhood volunteers and Coalition members to conduct face-to-face interviews
      with residents about their health and health care access. Subsequently, the
      Coalition surveyed 138 residents, and the agency now possesses extensive data
      about the nature and extent of health problems in their community. Lessons
      learned from these experiences are offered.

PMID- 24871771
TI  - Urbanization as a determinant of health: a socioepidemiological perspective.
AB  - Urbanization is a process that leads to the growth of cities due to
      industrialization and economic development and that leads to urban-specific
      changes. Urbanization is associated with profound changes in diet and exercise
      that in turn increase the prevalence of obesity with attendant increases in risk
      of type II diabetes and cardiovascular disease. The growing burden of disease
      among vulnerable populations and pervasive socioeconomic inequities within urban
      systems exaggerates the adverse impacts of urbanization on health. More than one
      half of children younger than age 5 of urban poor are stunted and/or underweight.
      More than one half of the child births occur at home, in slums, putting the life
      of the mother and newborn in serious risk. Inadequate reach of services due to
      illegality, social exclusion of slums, hidden slum pockets, and weak social
      fabric have resulted in a rapid proliferation of the unqualified private health
      sector, leading to high health expenditures and continuing a vicious cycle of
      poverty and ill health in urban slums.

PMID- 24871772
TI  - Caste-, work-, and descent-based discrimination as a determinant of health in
      social epidemiology.
AB  - Social epidemiology explores health in the context of broad social determinants
      of health, where the boundary lines between health and politics appear
      increasingly blurred. Social determinants of health such as caste,
      discrimination, and social exclusion are inherently political in nature, hence it
      becomes imperative to look at health through a broader perspective of political
      philosophy, ideology, and caste that imposes enormous obstacles to a person's
      full attainment of civil, political, economic, social, and cultural rights. Caste
      is descent based and hereditary in nature. It is a characteristic determined by
      one's birth into a particular caste, irrespective of the faith practiced by the
      individual. Caste denotes a system of rigid social stratification into ranked
      groups defined by descent and occupation. Under various caste systems throughout
      the world, caste divisions also dominate in housing, marriage, and general social
      interaction divisions that are reinforced through the practice and threat of
      social ostracism, economic boycotts, and even physical violence-all of which
      undermine health equality.

PMID- 24871774
TI  - School-based vaccination programs and the HPV vaccine in 16 Appalachian Kentucky
      school districts: results from a pilot study.
AB  - The purpose of this article is to describe a pilot study of 16 Appalachian
      Kentucky school districts designed to gather information about their school
      vaccination and health education programs in relation to the Human Papillomavirus
      (HPV) vaccine. School district administrators were contacted by a professional
      telephone interviewer and asked to participate in a structured interview that
      also included open-ended questions. Results suggest that few schools have school
      based vaccination programs, and of those that do, very few programs include the
      HPV vaccine. A majority of respondents reported that information leaflets about
      HPV are available in the schools, whereas few schools include discussions of HPV
      in their health programs. Almost all respondents reported an excellent
      relationship with their county health departments, school nurses, and school
      social workers, although most schools lacked the presence of a school social
      worker. Implications for social work practice and policy and directions for
      future research are also discussed.

PMID- 24871773
TI  - Exploring the role of social interactions and supports in overcoming
      accessibility barriers while undertaking health tours in India.
AB  - This article explores the phenomenon of companionship as an adaptation strategy
      to counter the existing barriers to health care access in developing nations.
      Companionship is argued to be an outcome of "inter" and "intra" household
      collaboration to offer diverse supports in addition to altruism. The analysis of
      the household survey conducted in West Bengal, India, exhibited different
      patterns of health care tours and the associated dependencies. In addition to
      support in terms of mobility while traveling and companionship while waiting for
      the opportunity, support in terms of refuge is also found to be essential,
      especially for the poor while they undertake regional tours. Causal models
      focusing on aggregated general health tours and specific regional tours were
      estimated separately to comprehend the implicit social interactions and their
      effects on the patient as well as the companions. The research demonstrated that
      accessibility barriers affect not only the ill, but also those associated with
      them and at times adversely. Segregation of regional tours illustrated the gaps,
      which instigated such tours and also might aid in health infrastructure planning
      as a whole.

PMID- 24871776
TI  - Geodermatophilus brasiliensis sp. nov., isolated from Brazilian soil.
AB  - A Gram-reaction-positive bacterial isolate, designated Tu 6233(T), with
      rudimentary, coral-pink vegetative mycelium that formed neither aerial mycelium
      nor spores, was isolated from a Brazilian soil sample. Chemotaxonomic and
      molecular characteristics of the isolate matched those described for members of
      the genus Geodermatophilus. Cell-wall hydrolysates contained meso-diaminopimelic
      acid as the diagnostic diamino acid and galactose as the diagnostic sugar. The
      major fatty acids were iso-C(16 : 0), iso-C(15 : 0) and C(17 : 1)omega8c and the
      predominant menaquinone was MK-9(H4). The polar lipids consisted of
      diphosphatidylglycerol, phosphatidylethanolamine,
      hydroxyphosphatidylethanolamine, phosphatidylinositol, an unknown
      glycophospholipid and an unknown phospholipid. The DNA G+C content of the strain
      was 75.4 mol%. The 16S rRNA gene sequence identity with members of the genus
      Geodermatophilus was 94.2-98.7%. Based on phenotypic, chemotaxonomic and
      phylogenetic data, strain Tu 6233(T) is proposed to represent a novel species,
      Geodermatophilus brasiliensis sp. nov., with the type strain Tu 6233(T) ( = DSM
      44526(T) = CECT 8402(T)).

PMID- 24871777
TI  - Bacillus fengqiuensis sp. nov., isolated from a typical sandy loam soil under
      long-term fertilization.
AB  - A Gram-staining-positive, endospore-forming, moderately alkaliphilic bacterium,
      strain NPK15(T), was isolated from a typical sandy loam soil under long-term NPK
      fertilization in northern China and was subjected to a polyphasic taxonomic
      study. The diamino acid of the cell-wall peptidoglycan of strain NPK15(T) was
      found to be meso-diaminopimelic acid and the cell-wall sugars were xylose,
      glucose and traces of mannose. The only respiratory quinone found in strain
      NPK15(T) was menaquinone 7 (MK-7). The major cellular fatty acids were iso-C(15 :
      0), anteiso-C(15 : 0), C(16 : 0) and C(16 : 1)omega6c/C(16 : 1)omega7c. The major
      polar lipids were diphosphatidylglycerol, phosphatidylethanolamine and
      phosphatidylglycerol. Phylogenetic analysis of the strain based on its 16S rRNA
      gene sequence showed that it was related most closely to 'Bacillus thaonhiensis'
      KACC 17216 (99.59%), B. songklensis KCTC 13881(T) (99.52%) and B. abyssalis CCTCC
      AB 2012074(T) (99.00%). DNA-DNA hybridization results indicated that the strain
      was distinct from other species of the genus Bacillus, the degree of relatedness
      being 35.4% with B. abyssalis CCTCC AB 2012074(T), 39.7% with B. songklensis KCTC
      13881(T) and 51.2% with 'B. thaonhiensis' KACC 17216. The DNA G+C content of
      strain NPK15(T) was 45.5 mol%. Phenotypic, chemotaxonomic and molecular analyses
      identified strain NPK15(T) as a member of a novel species of the genus Bacillus,
      for which the name Bacillus fengqiuensis sp. nov. is proposed. The type strain is
      NPK15(T) ( = DSM 26745(T) = CCTCC AB 2013156(T)).

PMID- 24871778
TI  - Leiothecium cristatum sp. nov. and Aspergillus posadasensis sp. nov., two species
      of Eurotiales from rainforest soils in South America.
AB  - We describe two novel fungi isolated from soil samples collected in Northern
      Argentina and belonging to the family Aspergillaceae of the order Eurotiales:
      Leiothecium cristatum sp. nov. and Aspergillus posadasensis sp. nov. Leiothecium
      cristatum sp. nov., represented by the ex-type strain FMR 11998(T) ( = CBS
      134260(T) = NBRC 109843(T)), is distinguishable morphologically from the type
      species of the genus, Leiothecium ellipsoideum, by the presence of irregular
      reticulate ascospores with two prominent equatorial crests, and Aspergillus
      posadasensis sp. nov., represented by the ex-type strain FMR 12168(T) ( = CBS
      134259(T) = NBRC 109845(T)), is differentiated from Aspergillus acanthosporus,
      the nearest species phylogenetically, by its non-sclerotioid ascomata and a lack
      of an asexual stage on all culture media tested. The taxonomic proposals are
      supported by the analysis of the sequences of the internal transcribed spacer
      region, the D1-D2 domains of the 28S rRNA gene, the fragments of the RNA
      polymerase II largest subunit, and the putative chaperonin complex related to TCP
      1, beta-tubulin and calmodulin genes. 

PMID- 24871779
TI  - Paenibacillus dongdonensis sp. nov., isolated from rhizospheric soil of Elymus
      tsukushiensis.
AB  - A Gram-staining-positive, endospore-forming and rod-shaped bacterial strain,
      designated KUDC0114(T), was isolated from rhizospheric soil of Elymus
      tsukushiensis from Dongdo Island, one of the largest of the Dokdo Islands, South
      Korea. The strain displayed optimal growth at 37  degrees C, pH 8.5 in the
      absence of NaCl. Based on phylogenetic analysis of 16S rRNA gene sequences,
      strain KUDC0114(T) represented a member of the genus Paenibacillus and was most
      closely related to Paenibacillus taichungensis BCRC 17757(T) (98.46%). The cell
      wall peptidoglycan was A1gamma type, and the predominant quinone was menaquinone
      7 (MK-7). The major cellular fatty acids were anteiso-C(15 : 0) and C(16 : 0).
      The DNA-DNA hybridization of strain KUDC0114(T) with nine other strains indicated
      less than 23% relatedness, and its DNA G+C content was 44.30 mol%. Based on
      genomic, phenotypic and phylogenetic analyses, KUDC0114(T) should be classified
      as representing novel species within the genus Paenibacillus. The name
      Paenibacillus dongdonensis sp. nov. is proposed. The type strain is KUDC0114(T) (
      = DSM27607(T) = KCTC33221(T)).

PMID- 24871780
TI  - Pure laparoscopic right hepatectomy with the hanging maneuver for multiple
      hepatocellular adenomas.
AB  - A 54-year-old woman with multiple telangiectatic hepatocellular adenoma without
      degeneration (>5 cm) underwent laparoscopic right hepatectomy with the hanging
      maneuver. The patient was installed in the supine position with the legs spread
      apart. Five trocars were used for the intervention. The liver hanging maneuver
      was performed up-to-down with a nasogastric tube and no prior mobilization of the
      right liver. Surgery lasted 270 min with 100 ml of blood loss and 15 min of
      hepatic pedicle clamping. The patient was discharged on postoperative day 7. This
      anterior approach avoids difficult mobilization of the right liver, guides the
      anatomical transaction plane, limits bleeding, and increases the number of
      patients who can benefit from the laparoscopic approach. 

PMID- 24871768
TI  - Pharmacokinetics and pharmacodynamics of antibacterials, antifungals, and
      antivirals used most frequently in neonates and infants.
AB  - Antimicrobials and antivirals are widely used in young infants and neonates.
      These patients have historically been largely excluded from clinical trials and,
      as a consequence, the pharmacokinetics and pharmacodynamics of commonly used
      antibacterials, antifungals, and antivirals are incompletely understood in this
      population. This review summarizes the current literature specific to neonates
      and infants regarding pharmacokinetic parameters and changes in neonatal
      development that affect antimicrobial and antiviral pharmacodynamics. Specific
      drug classes addressed include aminoglycosides, aminopenicillins, cephalosporins,
      glycopeptides, azole antifungals, echinocandins, polyenes, and guanosine analogs.
      Within each drug class, the pharmacodynamics, pharmacokinetics, and clinical
      implications and future directions for prototypical agents are discussed. beta
      Lactam antibacterial activity is maximized when the plasma concentration exceeds
      the minimum inhibitory concentration for a prolonged period, suggesting that more
      frequent dosing may optimize beta-lactam therapy. Aminoglycosides are typically
      administered at longer intervals with larger doses in order to maximize exposure
      (i.e., area under the plasma concentration-time curve) with gestational age and
      weight strongly influencing the pharmacokinetic profile. Nonetheless, safety
      concerns necessitate therapeutic drug monitoring across the entire neonatal and
      young infant spectrum. Vancomycin, representing the glycopeptide class of
      antibacterials, has a long history of clinical utility, yet there is still
      uncertainty about the optimal pharmacodynamic index in neonates and young
      infants. The high degree of pharmacokinetic variability in this population makes
      therapeutic drug monitoring essential to ensure adequate therapeutic exposure.
      Among neonates treated with the triazole agent fluconazole, it has been
      speculated that loading doses may improve pharmacodynamic target attainment
      rates. The use of voriconazole necessitates therapeutic drug monitoring and dose
      adjustments for patients with hepatic dysfunction. Neonates treated with lipid
      based formulations of the polyene amphotericin B may be at an increased risk of
      death, such that alternative antifungal agents should be considered for neonates
      with invasive fungal infections. Alternative antifungal agents such as micafungin
      and caspofungin also exhibit unique pharmacokinetic considerations in this
      population. Neonates rapidly eliminate micafungin and require nearly three times
      the normal adult dose to achieve comparable levels of systemic exposure.
      Conversely, peak caspofungin concentrations have been reported to be similar
      among neonates and adults. However, both of these drugs feature favorable safety
      profiles. Recent studies with acyclovir have suggested that current dosing
      regimens may not result in therapeutic central nervous system concentrations and
      more frequent dosing may be required for neonates at later postmenstrual ages.
      Though ganciclovir and valganciclovir demonstrate excellent activity against
      cytomegalovirus, they are associated with significant neutropenia. In summary,
      many pharmacokinetic and pharmacodynamic studies have been conducted in this
      vulnerable population; however, there are also substantial gaps in our knowledge
      that require further investigation. These studies will be invaluable in
      determining optimal neonatal dosing regimens that have the potential to improve
      clinical outcomes and decrease adverse effects associated with antimicrobial and
      antiviral treatments. 

PMID- 24871782
TI  - Molecular beam epitaxy growth and post-growth annealing of FeSe films on SrTiO3:
      a scanning tunneling microscopy study.
AB  - Low temperature scanning tunneling microscopy and spectroscopy are used to
      investigate the atomic and electronic structure evolution of FeSe films grown on
      SrTiO3 as a function of post-growth annealing. Single unit cell FeSe films are
      found to bond strongly with the underlying substrate, and become superconductive
      with diminishing chemical bond disorders at the interface via post-annealing. For
      thicker FeSe films, post-annealing removes excess Se in the films and leads to a
      transition from semiconductor into metallic behaviors. In double and multilayer
      films, strain-induced complex textures are observed and suggested to be the main
      cause for the absent superconductivity. 

PMID- 24871781
TI  - Preoperative characteristics of patients with presumed pancreatic cancer but
      ultimately benign disease: a multicenter series of 344 pancreatoduodenectomies.
AB  - BACKGROUND: Preoperative differentiation between malignant and benign pancreatic
      tumors can be difficult. Consequently, a proportion of patients undergoing
      pancreatoduodenectomy for suspected malignancy will ultimately have benign
      disease. The aim of this study was to compare preoperative clinical and
      diagnostic characteristics of patients with unexpected benign disease after
      pancreatoduodenectomy with those of patients with confirmed (pre)malignant
      disease. METHODS: We performed a multicenter retrospective cohort study in 1,629
      consecutive patients undergoing pancreatoduodenectomy for suspected malignancy
      between 2003 and 2010 in 11 Dutch centers. Preoperative characteristics were
      compared in a benign:malignant ratio of 1:3. Malignant cases were selected from
      the entire cohort by using a random number list. A multivariable logistic
      regression prediction model was constructed to predict benign disease. RESULTS:
      Of 107 patients (6.6 %) with unexpected benign disease after
      pancreatoduodenectomy, 86 fulfilled the inclusion criteria and were compared with
      258 patients with (pre)malignant disease. Patients with benign disease presented
      more often with pain (56 vs. 38 %; P = 0.004), but less frequently with jaundice
      (60 vs. 80 %; P < 0.01), a pancreatic mass (13 vs. 54 %, P < 0.001), or a double
      duct sign on computed tomography (21 vs. 47 %; P < 0.001). In a prediction model
      using these parameters, only 19 % of patients with benign disease were correctly
      predicted, and 1.4 % of patients with malignant disease were missed. CONCLUSIONS:
      Nearly 7 % of patients undergoing pancreatoduodenectomy for suspected malignancy
      were ultimately diagnosed with benign disease. Although some preoperative
      clinical and imaging characteristics might indicate absence of malignancy, their
      discriminatory value is insufficient for clinical use.

PMID- 24871785
TI  - Litigation claims relating to venous thromboembolism in the NHS.
AB  - AIM: Litigation costs for clinical negligence in the management of venous
      thromboembolism have escalated in the last five years. The National Health
      Service Litigation Authority estimates these claims have cost in excess of L112
      million. Our aim is to identify the areas of practice where these claims are most
      likely to arise to help improve patient outcome. METHODS: The National Health
      Service Litigation Authority provided de-identified data on individual medical
      negligence claims against the NHS since 2007. We subcategorised the data into (a)
      the nature of the venous thromboembolism event, (b) the area of specialist
      practice and (c) the damages incurred. Inter-group differences were evaluated
      using ANOVA, Kruskal-Wallis test and Mann-Whitney U Test. RESULTS: Failure to
      prevent and to diagnose pulmonary emboli and deep vein thrombosis occurs across
      the spectrum of clinical specialties. In the study period 189 claims were made.
      The majority of claims were in surgical specialties and the financial burden was
      significantly greater than in the medical specialities (L3,257,394 vs.
      L1,532,996). The amounts paid out by specialty was not significantly different
      but had significant variance (p < 0.0001). CONCLUSIONS: The National Institute of
      Clinical Excellence provides comprehensive guidelines on venous thromboembolism
      risk assessment. Poor compliance has contributed to morbidity and mortality while
      the cost has continued to escalate. A multimodal approach to education is needed
      to improve patient outcome. Improved venous thromboembolism prevalence data are
      also needed.

PMID- 24871786
TI  - Transient receptor potential melastatin 7 (TRPM7) contributes to H2O2-induced
      cardiac fibrosis via mediating Ca(2+) influx and extracellular signal-regulated
      kinase 1/2 (ERK1/2) activation in cardiac fibroblasts.
AB  - Transient receptor potential melastatin 7 (TRPM7), a Ca(2+)-nonselective cation
      channel, plays a key role in the pathophysiological response of multiple cell
      types. However, the role of TRPM7 channels in hydrogen peroxide (H2O2)-induced
      cardiac fibrosis remains unclear. This study aimed to explore whether TRPM7
      channels are involved in H2O2-induced cardiac fibrosis and the underlying
      mechanisms. Our results showed that 2-aminoethoxydiphenylborate (2-APB), which is
      commonly used to block TRPM7 channels, inhibited H2O2-induced cardiac fibrosis
      via attenuating the overexpression of important fibrogenic biomarkers and growth
      factors in cardiac fibroblasts, including collagen type I (Col I), fibronectin
      (FN), smooth muscle alpha-actin (alpha-SMA), connective tissue growth factor
      (CTGF), and transforming growth factor-beta1 (TGF-beta1). In addition, 2-APB also
      decreased H2O2-mediated elevation of the concentration of intracellular Ca(2+)
      ([Ca(2+)]i). Meanwhile, silencing TRPM7 channels by shRNA interference also
      impaired the increased [Ca(2+)]i and upregulation of Col I, FN, alpha-SMA, CTGF,
      and TGF-beta1 induced by H2O2. Furthermore, we found that H2O2-mediated
      activation of extracellular signal-regulated kinase 1/2 (ERK1/2) decreased in
      TRPM7-shRNA cells and Ca(2+)-free culture media. These results demonstrated that
      TRPM7 channels contributed to H2O2-induced cardiac fibrosis and suggested that
      this contribution may be through mediating Ca(2+) influx and phosphorylation of
      ERK1/2. 

PMID- 24871783
TI  - Surgical management of locally advanced lung cancer.
AB  - Majority of cases of lung cancer are detected at an advanced stage; such patients
      are usually treated with chemotherapy and radiotherapy, and the prognosis is
      frequently poor. Surgical resection remains the only reliable curative method for
      the treatment of lung cancer, and combined resection of the primary tumor and
      involved neighboring structures is performed when possible in patients with
      locally advanced disease. In the TNM classification, tumors with direct
      extrapulmonary extension are subdivided based on the anatomic extent of disease
      and its potential for surgical treatment: T3 lesions with limited, circumscribed
      extension are thought to be potentially surgically resectable, whereas T4 tumors
      with extensive extension are considered unresectable. Although surgical treatment
      for T3 lesions is generally accepted, the outcome is frequently not satisfactory.
      On the other hand, advanced surgical techniques are now being applied for T4
      lesions due to improvements in surgery and anesthesiology and progress in
      combined treatment modalities. In the present staging, T4N0-1M0 lesions are
      categorized as stage IIIA disease, and T4 tumors without mediastinal nodal
      metastasis are now considered to be potentially curable if complete resection is
      possible. This article reviews the modern surgical management of patients with
      lung cancer invading neighboring structures, including the chest wall, superior
      sulcus, diaphragm, tracheal carina, left atrium, superior vena cava, aorta and
      vertebrae. Furthermore, the surgical treatment of carcinomatous pleuritis, which
      was categorized as T4 disease in the previous TNM classification, is also
      assessed, and the role of surgical resection in cases of locally advanced lung
      cancer is discussed. 

PMID- 24871788
TI  - Paper electrochemical device for detection of DNA and thrombin by target-induced
      conformational switching.
AB  - Here, we report a strategy for the design of an inexpensive paper analytical
      device (PAD) for quantitative detection of oligonucleotides and proteins.
      Detection is based on the principle of target-induced conformational switching of
      an aptamer linked to an electrochemical label. This simple and robust method is
      well matched to the equally simple and robust characteristics of the PAD
      platform. The demonstrated limits of detection for DNA and thrombin are 30 nM and
      16 nM, respectively, and the device-to-device reproducibility is better than +/
      10%. The PAD has a shelf life of at least 4 weeks, involves little user
      intervention, and requires a sample volume of just 20 MUL. 

PMID- 24871789
TI  - Call me--mobile telephone blues.

PMID- 24871787
TI  - A comparative study of DA-9601 and misoprostol for prevention of NSAID-associated
      gastroduodenal injury in patients undergoing chronic NSAID treatment.
AB  - Misoprostol is reported to prevent non-steroidal anti-inflammatory drug (NSAID)
      associated gastroduodenal complications. There is, however, limited information
      regarding the efficacy of DA-9601 in this context. We performed a comparative
      study on the relative efficacy of DA-9601 and misoprostol for prevention of NSAID
      associated complications. In this multicenter, double-blinded, active-controlled,
      stratified randomized, parallel group, non-inferiority trial, 520 patients who
      were to be treated with an NSAID (aceclofenac, 100 mg, twice daily) over a 4-week
      period were randomly assigned to groups for coincidental treatment with DA-9601
      (60 mg, thrice daily) (236 patients for full analysis) or misoprostol (200 MUg,
      thrice daily) (242 patients for full analysis). [corrected]. The primary endpoint
      was the gastric protection rate, and secondary endpoints were the duodenal
      protection rate and ulcer incidence rate. Endpoints were assessed by endoscopy
      after the 4-week treatment period. Drug-related adverse effects, including
      gastrointestinal (GI) symptoms, were also compared. At week 4, the gastric
      protection rates with DA-9601 and misoprostol were 81.4 % (192/236) and 89.3 %
      (216/242), respectively. The difference between the groups was -14.2 %,
      indicating non-inferiority of DA-9601 to misoprostol. Adverse event rates were
      not different between the two groups; however, the total scores for GI symptoms
      before and after administration were significantly lower in the DA-9601 group
      than in the misoprostol group (-0.2 +/- 2.8 vs 1.2 +/- 3.2; p < 0.0001). DA-9601
      is as effective as misoprostol in preventing NSAID-associated gastroduodenal
      complications, and has a superior adverse GI effect profile.

PMID- 24871790
TI  - Parental adaptation to out-of-home placement of a child with severe or profound
      developmental disabilities.
AB  - Utilizing grounded theory qualitative research methods, a model was developed for
      describing parental adaptation after voluntary placement of a child with severe
      or profound developmental disabilities in out-of-home care. Interviews of parents
      from 20 families were analyzed. Parents' cognitive appraisals of placement
      outcomes were classified as either inducing emotional stress (i.e., guilt,
      sadness, fear and worry, anger and frustration, and uncertainty) or relief.
      Parental appraisals of responses to placement by children, extended family, and
      friends were identified as factors affecting the parents' adaptation to
      placement. The primary coping methods used by parents to decrease emotional
      stress and increase relief consisted of reappraisals regarding the necessity of
      placement, involvement in the child's life, psychotherapy, and the passage of
      time.

PMID- 24871792
TI  - A longitudinal follow-up study of affect in children and adults with Cornelia de
      Lange syndrome.
AB  - Studies of individuals with Cornelia de Lange syndrome (CdLS) have described
      changes in mood and behavior with age, although no empirical or longitudinal
      studies have been conducted. Caregivers of individuals with CdLS (N  =  67), cri
      du chat syndrome (CdCS; N  =  42), and Fragile X syndrome (FXS; N  =  142)
      completed the Mood, Interest and Pleasure Questionnaire (MIPQ) at Time 1 and 2
      years later (Time 2). Scores on the MIPQ were significantly lower in the CdLS
      group compared with the CdCS and FXS groups at Time 1 and Time 2. Lower MIPQ
      scores were characteristic of older adolescents (> 15 years) and adults with
      CdLS. However, there were no significant differences in MIPQ scores between Time
      1 and Time 2. Age and insistence on sameness predicted MIPQ scores in CdLS.

PMID- 24871791
TI  - Rule-based category learning in Down syndrome.
AB  - Rule-based category learning was examined in youths with Down syndrome (DS),
      youths with intellectual disability (ID), and typically developing (TD) youths.
      Two tasks measured category learning: the Modified Card Sort task (MCST) and the
      Concept Formation test of the Woodcock-Johnson-III ( Woodock, McGrew, & Mather,
      2001 ). In regression-based analyses, DS and ID groups performed below the level
      expected for their nonverbal ability. In cross-sectional developmental trajectory
      analyses, results depended on the task. On the MCST, the DS and ID groups were
      similar to the TD group. On the Concept Formation test, the DS group had slower
      cross-sectional change than the other 2 groups. Category learning may be an area
      of difficulty for those with ID, but task-related factors may affect trajectories
      for youths with DS.

PMID- 24871793
TI  - Epidemiology of epilepsy in older adults with an intellectual disability in
      Ireland: associations and service implications.
AB  - There are limited studies on the prevalence of epilepsy and co-morbid conditions
      in older adults with an ID. To begin to address this prevalence of epilepsy was
      estimated for participants in the Intellectual Disability Supplement to the Irish
      Longitudinal Study on Ageing. Associations with demographic variables and co
      morbid health conditions were examined. It was found that prevalence was high
      (30.7%); but declined as people aged. Those with epilepsy were less likely to
      live with family, independently or in community settings, rates of refractory
      epilepsy were high and, despite medication over half of those with epilepsy still
      reported experiencing seizures. Given these findings, people with ID and their
      careers have considerable needs for information about epilepsy management, and
      for support from specialist ID and epilepsy services.

PMID- 24871794
TI  - Individuals with 22q11.2 deletion syndrome are impaired at explicit, but not
      implicit, discrimination of local forms embedded in global structures.
AB  - Individuals with 22q11.2 deletion syndrome (22q11.2DS) are impaired at exploring
      visual information in space; however, not much is known about visual form
      discrimination in the syndrome. Thirty-five individuals with 22q11.2DS and 41
      controls completed a form discrimination task with global forms made up of local
      elements. Affected individuals demonstrated clear impairment in detecting local,
      but not global, differences. Nevertheless, 22q11.2DS participants easily
      discriminated the same local elements when they were displayed in isolation, and
      further use of a prime demonstrated preserved facilitation of local processing in
      22q11.2DS. These results did not differ by age or IQ. This study illustrates the
      impact of visuospatial impairments on form discrimination, and suggests how these
      difficulties may affect visual scanning in 22q11.2DS.

PMID- 24871795
TI  - An interactive multimedia program to prevent HIV transmission in men with
      intellectual disability.
AB  - The efficacy of a computer-based interactive multimedia HIV/AIDS prevention
      program for men with intellectual disability (ID) was examined using a quasi
      experimental within-subjects design. Thirty-seven men with mild to moderate
      intellectual disability evaluated the program. The pretest and posttest
      instruments assessed HIV/AIDS knowledge (high-risk fluids, HIV transmission, and
      condom facts) and condom application skills. All outcome measures showed
      statistically significant gains from pretest to posttest, with medium to large
      effect sizes. In addition, a second study was conducted with twelve service
      providers who work with men with ID. Service providers reviewed the HIV/AIDS
      prevention program, completed a demographics questionnaire, and a program
      satisfaction survey. Overall, service providers rated the program highly on
      several outcome measures (stimulation, relevance, and usability).

PMID- 24871799
TI  - How can you manage your patients without 'breakpoint'?

PMID- 24871798
TI  - Effects of electroconvulsive seizures on depression-related behavior, memory and
      neurochemical changes in Wistar and Wistar-Kyoto rats.
AB  - BACKGROUND: Investigations in healthy outbred rat strains have shown a potential
      role for brain-derived neurotrophic factor (BDNF) and the hypothalamic-pituitary
      adrenal (HPA) axis in the antidepressant and memory side effects of
      electroconvulsive therapy (ECT, or ECS in animals). The Wistar-Kyoto (WKY) rat
      strain is used as a genetic model of depression yet no studies to date have
      directly compared the impact of ECS on the WKY strain to its healthy outbred
      control (Wistar). OBJECTIVE: The objective of this study is to examine behavioral
      (antidepressant and retrograde memory) and neurochemical (BDNF and HPA axis)
      changes immediately (1day) and at a longer delay (7days) after repeated ECS (5
      daily administrations) in WKY and Wistar rats. METHODS: Male Wistar and WKY rats
      received 5days of repeated ECS or sham treatment and were assessed 1 and 7days
      later for 1) depression-like behavior and mobility; 2) retrograde memory; and 3)
      brain BDNF protein, brain corticotropin-releasing factor (CRF) and plasma
      corticosterone levels. RESULTS: Both strains showed the expected antidepressant
      response and retrograde memory impairments at 1day following ECS, which were
      sustained at 7days. In addition, at 1day after ECS, Wistar and WKY rats showed
      similar elevations in brain BDNF and extra-hypothalamic CRF and no change in
      plasma corticosterone. At 7days after ECS, Wistar rats showed sustained
      elevations of brain BDNF and CRF, whereas WKY rats showed a normalization of
      brain BDNF, despite sustained elevations of brain CRF. CONCLUSIONS: The model of
      5 daily ECS was effective at eliciting behavioral and neurochemical changes in
      both strains. A temporal association was observed between brain CRF levels, but
      not BDNF, and measures of antidepressant effectiveness of ECS and retrograde
      memory impairments suggesting that extra-hypothalamic CRF may be a potential
      important contributor to these behavioral effects after repeated ECS/ECT.

PMID- 24871800
TI  - A silent revolution in chromosome biology.

PMID- 24871801
TI  - Transcription: transcript elongation: pause at your peril.

PMID- 24871805
TI  - Neutrophil gelatinase B-associated lipocalin and matrix metalloproteinase-9
      complex as a surrogate serum marker of mucosal healing in ulcerative colitis.
AB  - BACKGROUND: The current standard for the assessment of mucosal healing after
      therapy in inflammatory bowel diseases is endoscopy. However, a high need exists
      for noninvasive, accurate surrogate markers. METHODS: In 2 independent cohorts,
      levels of serum neutrophil gelatinase B-associated lipocalin and matrix
      metalloproteinase-9 complex (NGAL-MMP-9) from patients with active ulcerative
      colitis (UC) before and after first treatment with infliximab and from healthy
      controls (HC) were determined with zymography and sandwich enzyme-linked
      immunosorbent assay. The response to infliximab was defined as complete mucosal
      healing (Mayo endoscopic subscore 0-1) at control endoscopy. Data were analyzed
      with SPSS, and P values <0.05 were considered significant. RESULTS: In cohort 1
      (n = 66; median age, 30 yr; 38% female), serum NGAL-MMP-9 levels significantly
      increased at baseline in UC patients versus HC (103.8 versus 42.4 ng/mL; P <
      0.0001), whereas 55% of the patients had normal C-reactive protein levels. NGAL
      MMP-9 levels significantly decreased after therapy in UC responders (from 116.3
      ng/mL to 32.0 ng/mL; P < 0.0001) and in nonresponders (from 94.7 ng/mL to 54.1
      ng/mL; P = 0.047). In cohort 2 (n = 132; median age, 39 yr; 53% female), NGAL-MMP
      9 levels increased at baseline in active UC patients versus HC (86.5 versus 60.4
      ng/mL; P = 0.10), whereas 45% of the patients had normal C-reactive protein
      levels. NGAL-MMP-9 levels significantly decreased after therapy in responders
      (from 87.5 ng/mL to 16.3 ng/mL; P < 0.0001) but not in nonresponders (from 82.7
      ng/mL to 57.8 ng/mL; P = 0.19). After pooling the data, a cutoff value of 97.7
      ng/mL for NGAL-MMP-9 complex was determined to predict complete mucosal healing
      with high specificity (91%). CONCLUSIONS: Serum NGAL-MMP-9 is suggested as a new
      surrogate marker for the assessment of mucosal healing in UC patients treated
      with infliximab.

PMID- 24871806
TI  - A bombesin-shepherdin radioconjugate designed for combined extra- and
      intracellular targeting.
AB  - Radiolabeled peptides which target tumor-specific membrane structures of cancer
      cells represent a promising class of targeted radiopharmaceuticals for the
      diagnosis and therapy of cancer. A potential drawback of a number of reported
      radiopeptides is the rapid washout of a substantial fraction of the initially
      delivered radioactivity from cancer cells and tumors. This renders the initial
      targeting effort in part futile and results in a lower imaging quality and
      efficacy of the radiotracer than achievable. We are investigating the combination
      of internalizing radiopeptides with molecular entities specific for an
      intracellular target. By enabling intracellular interactions of the
      radioconjugate, we aim at reducing/decelerating the externalization of
      radioactivity from cancer cells. Using the "click-to-chelate" approach, the 99mTc
      tricarbonyl core as a reporter probe for single-photon emission computed
      tomography (SPECT) was combined with the binding sequence of bombesin for
      extracellular targeting of the gastrin-releasing peptide receptor (GRP-r) and
      peptidic inhibitors of the cytosolic heat shock 90 protein (Hsp90) for
      intracellular targeting. Receptor-specific uptake of the multifunctional
      radioconjugate could be confirmed, however, the cellular washout of radioactivity
      was not improved. We assume that either endosomal trapping or lysosomal
      degradation of the radioconjugate is accountable for these observations. 

PMID- 24871809
TI  - Cyclodextrin-based supramolecular nanoparticles stabilized by balancing
      attractive host-guest and repulsive electrostatic interactions.
AB  - Multicomponent, negatively charged supramolecular nanoparticles (SNPs) were
      formed by multivalent host-guest interactions without the need of a stopper in
      water and in PBS. Their size and stability are controlled owing to a balance of
      forces between attractive supramolecular and repulsive electrostatic
      interactions. 

PMID- 24871808
TI  - Comparative safety and efficacy of two formulations of mometasone nasal spray in
      adult seasonal allergic rhinitis.
AB  - Mometasone furoate as a nasal spray is an effective treatment for seasonal
      allergic rhinitis (SAR). An aqueous mometasone nasal spray containing the same
      active substance and excipients as the originator product (reference mometasone)
      has been developed. This study was designed to establish therapeutic equivalence
      of test mometasone to reference mometasone and superiority over placebo for the
      treatment of SAR in adults. In this multicenter, randomized, double-blind,
      placebo- and active-controlled, fixed-dose study, patients aged >=18 years with
      SAR were randomized 2:2:1 to reference mometasone, test mometasone, or placebo
      for 28 days. Patients recorded nasal and ocular symptoms daily. The primary end
      point was change from baseline in the pooled 24-hour reflective total nasal
      symptom score (rTNSS). Safety and tolerability included evaluation by adverse
      events (AEs), physical (including nasal) examinations, vital signs assessments,
      laboratory evaluations, and change in concomitant medications. Four hundred two
      patients received reference mometasone (n = 156), test mometasone (n = 163), or
      placebo (n = 83). The intent-to-treat population (ITT) comprised 399 patients,
      and the per-protocol (PP) population comprised 327 patients. The 95% confidence
      intervals for the treatment difference (reference minus test mometasone) in
      change from baseline in pooled 24-hour rTNSS were within prespecified equivalence
      limits for the PP and ITT populations. Both active treatments showed superiority
      over placebo (p = 0.0019-0.0087). No significant difference was seen between test
      mometasone and reference mometasone for any secondary efficacy variables.
      Treatment-emergent AE incidence was low. No deaths or serious AEs were reported.
      The test mometasone is efficacious in the treatment of SAR in adults and shows a
      favorable safety profile. The results indicate that the test mometasone is
      therapeutically equivalent to the reference mometasone.

PMID- 24871807
TI  - A novel splicing silencer generated by DMD exon 45 deletion junction could
      explain upstream exon 44 skipping that modifies dystrophinopathy.
AB  - Duchenne muscular dystrophy (DMD), a progressive muscle-wasting disease, is
      mostly caused by exon deletion mutations in the DMD gene. The reading frame rule
      explains that out-of-frame deletions lead to muscle dystrophin deficiency in DMD.
      In outliers to this rule, deletion junction sequences have never previously been
      explored as splicing modulators. In a Japanese case, we identified a single exon
      45 deletion in the patient's DMD gene, indicating out-of-frame mutation. However,
      immunohistochemical examination disclosed weak dystrophin signals in his muscle.
      Reverse transcription-PCR amplification of DMD exons 42 to 47 revealed a major
      normally spliced product with exon 45 deletion and an additional in-frame product
      with deletion of both exons 44 and 45, indicating upstream exon 44 skipping. We
      considered the latter to underlie the observed dystrophin expression. Remarkably,
      the junction sequence cloned by PCR walking abolished the splicing enhancer
      activity of the upstream intron in a chimeric doublesex gene pre-mRNA in vitro
      splicing. Furthermore, antisense oligonucleotides directed against the junction
      site counteracted this effect. These indicated that the junction sequence was a
      splicing silencer that induced upstream exon 44 skipping. It was strongly
      suggested that creation of splicing regulator is a modifier of dystrophinopathy. 

PMID- 24871810
TI  - Surface behavior of hydrated guanidinium and ammonium ions: a comparative study
      by photoelectron spectroscopy and molecular dynamics.
AB  - Through the combination of surface sensitive photoelectron spectroscopy and
      molecular dynamics simulation, the relative surface propensities of guanidinium
      and ammonium ions in aqueous solution are characterized. The fact that the N 1s
      binding energies differ between these two species was exploited to monitor their
      relative surface concentration through their respective photoemission
      intensities. Aqueous solutions of ammonium and guanidinium chloride, and mixtures
      of these salts, have been studied in a wide concentration range, and it is found
      that the guanidinium ion has a greater propensity to reside at the aqueous
      surface than the ammonium ion. A large portion of the relative excess of
      guanidinium ions in the surface region of the mixed solutions can be explained by
      replacement of ammonium ions by guanidinium ions in the surface region in
      combination with a strong salting-out effect of guanidinium by ammonium ions at
      increased concentrations. This interpretation is supported by molecular dynamics
      simulations, which reproduce the experimental trends very well. The simulations
      suggest that the relatively higher surface propensity of guanidinium compared
      with ammonium ions is due to the ease of dehydration of the faces of the almost
      planar guanidinium ion, which allows it to approach the water-vapor interface
      oriented parallel to it. 

PMID- 24871811
TI  - In silico analysis reveals the anti-malarial potential of quinolinyl chalcone
      derivatives.
AB  - In this study, the correlation between chemical structures and various parameters
      such as steric effects and electrostatic interactions to the inhibitory
      activities of quinolinyl chalcone derivatives is derived to identify the key
      structural elements required in the rational design of potent and novel anti
      malarial compounds. The molecular docking simulations and Comparative Molecular
      Field Analysis (CoMFA) are carried out on 38 chalcones derivatives using
      Plasmodium falciparum lactate dehydrogenase (PfLDH) as potential target. Surflex
      dock is used to determine the probable binding conformations of all the compounds
      at the active site of pfLDH and to identify the hydrogen bonding interactions
      which could be used to alter the inhibitory activities. The CoMFA model has
      provided statistically significant results with the cross-validated correlation
      coefficient (q(2)) of .850 and the non-cross-validated correlation coefficient
      (r(2)) of .912. Standard error of estimation (SEE) is .280 and the optimum number
      of component is five. The predictive ability of the resultant model is evaluated
      using a test set comprising of 13 molecules and the predicted r(2) value is .885.
      The results provide valuable insight for optimization of quinolinyl chalcone
      derivatives for better anti-malarial therapy. 

PMID- 24871813
TI  - Relevance of hybridization and filling of 3d orbitals for the Kondo effect in
      transition metal phthalocyanines.
AB  - Magnetic organic molecules, such as 3d transition metal phthalocyanines (TMPc),
      exhibit properties which make them promising candidates for future applications
      in magnetic data storage or spin-based data processing. Due to their small size,
      however, TMPc molecules are prone to quantum effects. For example, the
      interaction of uncompensated molecular spins with conduction electrons of the
      substrate may lead to the formation of a many-body singlet state, which gives
      rise to the so-called Kondo effect. Although the Kondo effect of TMPc molecules
      has been the object of several investigations, a consistent picture to describe
      under which conditions a Kondo state is formed is still missing. Here, we study
      the Kondo properties of MnPc on Ag(001) by means of the low-temperature scanning
      tunneling spectroscopy (LT-STS) measurements. Differential conductance dI/dU
      spectra reveal a zero-bias peak that is localized on the Mn ion site. Ab initio
      calculations combined with a many-body treatment of the multiorbital interaction
      show that the local Hund coupling favors the high-spin configuration on the 3d
      shell of the central TM atom. Therefore, each orbital gets close to its
      individual half-filling creating the necessary condition for many of the 3d
      orbitals to contribute to the observed Kondo resonance. This, however, happens
      only for the 3dz(2) orbital, whose hybridization to the substrate is much
      stronger than for the other orbitals thanks to its shape and its orientation. 

PMID- 24871812
TI  - Ligand effects on the structural dimensionality and antibacterial activities of
      silver-based coordination polymers.
AB  - Four Ag-based coordination polymers [Ag(Bim)] (1), [Ag2(NIPH)(HBim)] (2), [Ag6(4
      NPTA)(Bim)4] (3) and [Ag2(3-NPTA)(bipy)0.5(H2O)] (4) (HBim = 1H-benzimidazole,
      bipy = 4,4'-bipyridyl, H2NIPH = 5-nitroisophthalic acid, H2NPTA = 3-/4
      nitrophthalic acid) have been synthesized by hydrothermal reaction of Ag(i) salts
      with N-/O-donor ligands. Single-crystal X-ray diffraction indicated that these
      coordination polymers constructed from mononuclear or polynuclear silver building
      blocks exhibit three typical structure features from 1-D to 3-D frameworks. These
      compounds favour a slow release of Ag(+) ions leading to excellent and long-term
      antimicrobial activities, which is distinguished by their different topological
      structures, towards both Gram-negative bacteria, Escherichia coli (E. coli) and
      Gram-positive bacteria, Staphylococcus aureus (S. aureus). In addition, these
      compounds show good thermal stability and light stability under UV-vis and
      visible light, which are important characteristics for their further application
      in antibacterial agents. 

PMID- 24871815
TI  - Acquired lymphangiectasia of the glans following circumcision.

PMID- 24871814
TI  - The effect of multiple injections of ranibizumab on retinal nerve fiber layer
      thickness in patients with age-related macular degeneration.
AB  - PURPOSE: To evaluate the effects of multiple intravitreal injections of
      ranibizumab on retinal nerve fiber layer (RNFL) thickness in patients with wet
      age-related macular degeneration (AMD). METHODS: This observational, comparative
      study included patients with 10 or more total ranibizumab injections and involved
      the measurement of RNFL thickness at baseline. Twenty-nine eyes of 29 consecutive
      patients were evaluated via intraocular pressure (IOP) and measurements of the
      total and nasal RNFL thicknesses at the initial and final follow-up by using
      optical coherence tomography. The RNFL thickness values of the fellow eyes and 27
      healthy eyes were used as the control group. The mean total and nasal RNFL
      thicknesses of the injection group were compared with those of the other two
      groups. At each visit, at every three injections, the IOP values of the study
      group were recorded and compared. The relationship between the number of
      injections and the mean RNFL thickness was assessed. RESULTS: The mean number of
      injections was 13.88 +/- 3.81 (10-24). The mean RNFL thickness of the injection
      group was 92.3 +/- 7.7 MUm at baseline and 92.46 +/- 8.1 MUm at the last follow
      up (p = 0.7). There were no statistically significant differences between the
      mean total and nasal RNFL thicknesses of the eyes with injections and the fellow
      eyes with no injections (p = 0.379, p = 0.897, respectively) or between those
      with injections and the healthy control group (p = 0.159, p = 0.273,
      respectively). There were no correlations between the number of injections and
      the mean total and nasal RNFL thicknesses (p = 0.854, p = 0.25, respectively).
      There was no statistical difference between the initial and final IOPs (p =
      0.760). CONCLUSION: Long-term treatment with anti-vascular endothelial growth
      factor (VEGF) agents did not lead to significant changes in RNFL thickness in a
      patient population with wet AMD. Chronic therapy with intravitreal anti-VEGF
      agents does not appear to adversely affect RNFL thickness.

PMID- 24871816
TI  - Evaluation of a community-based HIV preventive intervention for female sex
      workers in rural areas of Karnataka State, south India.
AB  - To examine changes in behavioral outcomes among rural female sex workers (FSWs)
      involved in a community-based comprehensive HIV preventive intervention program
      in south India. A total of 14, 284 rural FSWs were reached by means of a
      community-based model for delivering outreach, medical, and referral services.
      Changes in behavior were assessed using 2 rounds of polling booth surveys
      conducted in 2008 and 2011. In all, 95% of the mapped FSWs were reached at least
      once, 80.3% received condoms as per need, and 71% received health services for
      sexually transmitted infections. There was a significant increase in condom use
      (from 60.4% to 72.4%, P = .001) and utilization of HIV counseling and testing
      services (from 63.9% to 92.4%; P = .000) between the 2 time periods. This model
      for a community-based rural outreach and HIV care was effective and could also be
      applied to many other health problems. 

PMID- 24871817
TI  - B-DNA structure and stability: the role of hydrogen bonding, pi-pi stacking
      interactions, twist-angle, and solvation.
AB  - We have computationally investigated the structure and stability of B-DNA. To
      this end, we have analyzed the bonding in a series of 47 stacks consisting of two
      base pairs, in which the base pairs cover the full range of natural Watson-Crick
      pairs, mismatched pairs, and artificial DNA base pairs. Our analyses provide
      detailed insight into the role and relative importance of the various types of
      interactions, such as, hydrogen bonding, pi-pi stacking interactions, and
      solvation/desolvation. Furthermore, we have analyzed the functionality of the
      twist-angle on the stability of the structure. Interestingly, we can show that
      all stacked base pairs benefit from a stabilization by 6 to 12 kcal mol(-1) if
      stacked base pairs are twisted from 0 degrees  to 36 degrees , that is, if they
      are mutually rotated from a congruent superposition to the mutually twisted
      stacking configuration that occurs in B-DNA. This holds especially for stacked AT
      pairs but also for other stacked base pairs, including GC. The electronic
      mechanism behind this preference for a twisted arrangement depends on the base
      pairs involved. We also show that so-called "diagonal interactions" (or cross
      terms) in the stacked base pairs are crucial for understanding the stability of B
      DNA, in particular, in GC-rich sequences. 

PMID- 24871818
TI  - Electrochemical-induced dissolution of nickel-titanium endodontic instruments
      with different designs.
AB  - AIM: To compare the active dissolution process of K3, ProTaper and Mtwo NiTi
      endodontic rotary instruments in chloride and fluoride containing solutions.
      METHODS: Anodic polarization of K3 size 20, 0.06 taper, ProTaper size F1 and MTwo
      size 20, 0.06 taper instruments was performed, and anova (P < 0.05) was used to
      compare the weight loss, the time of dissolution and the electrical charge
      generated by the groups of instruments. Fragments of the instruments were
      polarized in simulated root canals to evaluate the dissolution process. After the
      tests, a size 10 K-file was used to verify whether the fragment could be
      bypassed. Radiographic analysis of the simulated canals was used before and after
      the tests to verify fragment dissolution. RESULTS: A progressive consumption of
      the instruments was observed. K3 and ProTaper instruments had significantly
      greater weight loss than Mtwo instruments after 30 min of polarization. K3
      instruments had the highest values of total electrical charge, and MTwo
      instruments the lowest (P < 0.05). After 60 min, the anodic polarization of
      instrument fragments in simulated root canals resulted in their partial
      dissolution. CONCLUSION: The anodic polarization of K3, ProTaper and MTwo
      instruments resulted in their progressive consumption with increasing
      polarization time. Sixty minutes anodic polarization of the various NiTi
      instrument fragments in simulated root canals resulted in their partial
      dissolution.

PMID- 24871820
TI  - Children's experiences of maternal incarceration-specific risks: predictions to
      psychological maladaptation.
AB  - Children of incarcerated mothers are at increased risk for social and emotional
      difficulties, yet few studies have investigated potential mechanisms of risk
      within this population. This research simultaneously examined the association of
      children's experience of incarceration-specific risk factors (e.g., witness
      mother's arrest) and environmental risks (e.g., low educational attainment) to
      children's psychological maladaptation using a multi-informant design and a
      latent variable analytic approach. Participants were 117 currently incarcerated
      mothers (64.1% African American), their 151 children (53.6% boys, M age = 9.8
      years, range = 6-12 years, 61.7% African American), and the 118 caregivers (74.8%
      female, 61.9% grandparents, 62.2% African American) of the children. Mothers,
      children, and caregivers each provided accounts of children's experiences related
      to maternal incarceration and children's internalizing and externalizing behavior
      problems. Mothers and caregivers each supplied information about 10 environmental
      risk factors. Findings from structural equation modeling indicate that children's
      incarceration-specific risk experiences predict internalizing and externalizing
      behavior problems whereas the influence of environmental risks was negligible.
      Follow-up analyses examining the contribution of specific risks indicate that
      significant predictors differ by reporter and separate into effects of family
      incarceration history and direct experiences of maternal incarceration.
      Incarceration-specific experiences place children at higher risk for
      maladjustment than exposure to general environmental risk factors. These findings
      indicate the need to critically examine children's exposure to experiences
      related to maternal incarceration and family incarceration history to help to
      clarify the multifaceted stressor of maternal incarceration.

PMID- 24871821
TI  - Risk for complications in patients with hemophagocytic lymphohistiocytosis who
      undergo hematopoietic stem cell transplantation: myeloablative versus reduced
      intensity conditioning regimens.
AB  - Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative
      option for patients with primary hemophagocytic lymphohistiocytosis (HLH) and for
      patients with secondary HLH who fail to respond to therapy. Advances in HSCT and
      supportive care measures have resulted in improved patient outcomes and decreased
      treatment-related mortality. Despite the overall improvement in outcome, HLH
      patients who undergo HSCT using myeloablative conditioning regimens are still at
      significant risk for complications. The HLH-94 study conducted by the Histiocyte
      Society reported a 30% TRM with increased pulmonary and hepatic complications.
      Recently, the use of reduced-intensity conditioning (RIC) regimens has shown
      favorable outcomes when compared to conventional HSCT and lower rate of acute
      complications. In this review we compare the potential complications of
      myeloablative and RIC regimens for HSCT in HLH patients. 

PMID- 24871822
TI  - Effects of intrathecal caffeic acid phenethyl ester and methylprednisolone on
      oxidant/antioxidant status in traumatic spinal cord injuries.
AB  - PURPOSE: To examine the effect of intrathecally given caffeic acid phenethyl
      ester (CAPE) on peroxidation and total oxidant and antioxidant systems, and the
      effect of intrathecally given methylprednisolone (MP) in spinal cord injury (SCI)
      models. MATERIALS AND METHODS: Four groups of 10 rats were formed: (1)
      Laminectomy, intrathecal saline injection, no SCI (sham: S); (2) Laminectomy,
      intrathecal saline injection, SCI (control: SCI); (3) Laminectomy, intrathecally
      given single dose of 3 mg/kg MP, SCISCI (SCI + MP). 4) Laminectomy, intrathecally
      given single dose of 1 ug/kg CAPE, SCI (SCI + CAPE). Malondialdehyde (MDA), total
      oxidant activity (TOA), total antioxidant capacity (TAC), superoxide dismutase
      (SOD), and glutathione peroxidase (GPx) values in the spinal cord tissue were
      evaluated. RESULTS: When group S and group SCI were compared, MDA, TOA, and SOD
      parameters increased post-SCI (p < 0.01). When compared with group SCI, it was
      observed that CAPE and MP decreased the MDA, TOA, and SOD levels (p < 0.01). This
      decrease was more pronounced in the SCI + CAPE group. When group S and group SCI
      were compared, a statistically substantial decrease was observed in the post-SCI
      TAC levels. When compared with group SCI, it was shown that CAPE and MP treatment
      substantially increased TAC levels (p < 0.001). CONCLUSION: Intrathecal injection
      of both CAPE and MP inhibits lipid peroxidation and increase of oxidants in SCIs.

PMID- 24871823
TI  - Neuroendoscopy and high-field intraoperative MRI: first experience.
AB  - BACKGROUND: To date, information about the use of intraoperative MRI (iMRI) in
      patients undergoing neuroendoscopic procedures is sparse. The benefit may be
      (re)definition of neuronavigation, confirmation of fenestrations and biopsies,
      detection of complications, and redefinition of anatomical changes during the
      operation. MATERIAL AND METHODS: Our setting consists of a fully integrated high
      field 1.5-T MRI into the operating room. The operating room can be functionally
      divided into (1) the MRI scanner and (2) the operating table outside the 5 Gauss
      line where ferromagnetic surgical instruments can be used. We included a
      consecutive series of 11 adult patients who underwent 11 endoscopic operations in
      the iMRI setting between January 2007 and September 2011. RESULTS: The median age
      of patients was 54 years (range: 40-69 years). The male-to-female ratio was
      4.5:1. Diagnoses leading to endoscopic treatment were aqueductal stenosis (n = 8;
      caused by tumors in three cases), pineal cyst (n = 1), tumor of the third
      ventricle (n = 1), and brain abscess with ventriculitis (n = 1). Endoscopic
      procedures were endoscopic third ventriculostomy with or without tumor biopsy (n
      = 5), aqueductoplasty (n = 4), tumor biopsy and septostomy (n = 1), and tumor
      resection (n = 1). All patients were scanned at least once, seven patients twice
      during surgery. The mean scan time per procedure was 19 minutes. The following
      sequences were regarded as most useful: T2 axial (placement of catheter, ruling
      out of complications), T2 sagittal (flow void signal), and true fast imaging
      (TRUFI) (fenestration defect). CONCLUSIONS: iMRI enables high-resolution imaging
      immediately after endoscopic operation. The combined use is technically feasible
      and of potential value in selected cases with complex hydrocephalus. In most of
      these cases, scanning can be limited to T2 axial, T2 sagittal, and TRUFI MR
      images.

PMID- 24871824
TI  - Nanostructure of an ionic liquid-glycerol mixture.
AB  - The nanostructure of a 50 : 50 vol% mixture of glycerol and ethylammonium formate
      (EAF), a protic ionic liquid (IL), has been investigated using neutron
      diffraction and empirical potential structure refinement (EPSR) fits. EPSR fits
      reveal that the mixture is nanostructured. Electrostatic interactions between IL
      charge groups leads to the formation of ionic regions. These solvophobically
      repel cation alkyl groups which cluster together to form apolar domains. The
      polar glycerol molecules are preferentially incorporated into the charged
      domains, and form hydrogen bonds with EAF groups rather than with other glycerol
      molecules. However, radial distribution functions reveal that glycerol molecules
      pack around each other in a fashion similar to that found in pure glycerol. This
      suggests that a glycerol channel runs through the ionic domain of EAF. The
      absence of significant glycerol-glycerol hydrogen bonding indicates that glycerol
      molecules are able to span the polar domain, bridging EAF charge groups. Glycerol
      can adopt six distinct conformations. The distribution of conformers in the EAF
      mixture is very different to that found in the pure liquid because hydrogen bonds
      form with EAF rather than with other glycerol molecules, which imparts different
      packing constraints. 

PMID- 24871825
TI  - Growth of Desulfovibrio vulgaris when respiring U(VI) and characterization of
      biogenic uraninite.
AB  - The capacity of Desulfovibrio vulgaris to reduce U(VI) was studied previously
      with nongrowth conditions involving a high biomass concentration; thus, bacterial
      growth through respiration of U(VI) was not proven. In this study, we conducted a
      series of batch tests on U(VI) reduction by D. vulgaris at a low initial biomass
      (10 to 20 mg/L of protein) that could reveal biomass growth. D. vulgaris grew
      with U(VI) respiration alone, as well as with simultaneous sulfate reduction.
      Patterns of growth kinetics and solids production were affected by sulfate and
      Fe(2+). Biogenic sulfide nonenzymatically reduced 76% of the U(VI) and greatly
      enhanced the overall reduction rate in the absence of Fe(2+) but was rapidly
      scavenged by Fe(2+) to form FeS in the presence of Fe(2+). Biogenic U solids were
      uraninite (UO2) nanocrystallites associated with 20 mg/g biomass as protein. The
      crystallite thickness of UO2 was 4 to 5 nm without Fe(2+) but was <1.4 nm in the
      presence of Fe(2+), indicating poor crystallization inhibited by adsorbed Fe(2+)
      and other amorphous Fe solids, such as FeS or FeCO3. This work fills critical
      gaps in understanding the metabolic utilization of U by microorganisms and
      formation of UO2 solids in bioremediation sites. 

PMID- 24871826
TI  - Seventeen new species and additional records of Lathrobium (Coleoptera,
      Staphylinidae) from mainland China.
AB  - Material of the paederine genus Lathrobium Gravenhorst, 1802 from the Chinese
      provinces Heilongjiang, Ningxia, Qinghai, Henan, Anhui, Zhejiang, Jiangxi, Hunan,
      Chongqing, Guizhou, Yunnan and Guangdong was examined. Twenty-one species were
      identified, seventeen of which are described as new: L. liuae (Heilongjiang:
      Hongwei); L. ningxiaense sp. n. (Ningxia: Heshangpu); L. baiyunense sp. n.
      (Henan: Baiyun Shan); L. ayui sp. n. (Anhui: Yaoluoping); L. yaoluopingense sp.
      n. (Anhui: Yaoluoping); L. chenae sp. n. (Zhejiang: Qingliangfeng); L. fengae sp.
      n. (Zhejiang: Qingliangfeng); L. gutianense sp. n. (Zhejiang: Gutian Shan); L.
      nannani sp. n. (Zhejiang: Gutian Shan); L. sanqingense sp. n. (Jiangxi: Sanqing
      Shan); L. badagongense sp. n. (Hunan: Badagong Shan); L. xui sp. n. (Chongqing:
      Huanggangou); L. fanjingense sp. n. (Guizhou: Fanjing Shan); L. lui sp. n.
      (Guizhou: Kuankuoshui); L. zhaigei sp. n. (Guizhou: Kuankuoshui); L. zizhiense
      sp. n. (Yunnan: Zizhi) and L. guangdongense sp. n. (Guangdong: Nanling). The
      female sexual characters of L. lingae Peng, Li & Zhao and L. longwangshanense
      Peng, Li & Zhao are described and illustrated for the first time. The junior
      primary homonym Lathrobium pilosum Peng & Li, 2012 is replaced with Lathrobium
      zhui nom. n. Including the new taxa described here, 189 Lathrobium species are
      currently known from the mainland China.  

PMID- 24871828
TI  - Catalogue of the type specimens deposited in the Mollusca Collection of the Museu
      Nacional / UFRJ, Rio de Janeiro, Brazil.
AB  - A curatorial revision of the type specimens deposited in the Mollusca Collection
      of the Museu Nacional / UFRJ, Rio de Janeiro, Brazil (MNRJ) revealed the
      existence of 518 lots of type specimens (holotypes, neotypes, syntypes and
      paratypes) for 285 names of molluscan taxa from 88 families, including 247
      gastropods, 30 bivalves, three cephalopods and five scaphopods. A total of 106
      holotypes and one neotype are deposited in the MNRJ. Type material for ten
      nominal taxa described as being deposited in the MNRJ was not located; the
      probable reasons are discussed. Some previously published erroneous information
      about types in the MNRJ is rectified. A total of 37 type specimens are
      illustrated. 

PMID- 24871827
TI  - A new rainfrog of the Pristimantis myersi Group (Amphibia, Craugastoridae) from
      Volcan Pichincha, Ecuador.
AB  - A new frog of the Pristimantis myersi Group is described from a bamboo patch
      within the Reserva Ecologica Verdecocha (0 degrees 5'46.9"S, 78 degrees
      36'15.3"W; 2851 m), located at northwestern flank of the Volcan Pichincha, in the
      vicinities of Quito, Ecuador. The new species is known from eight adult males,
      whereas the females remain unknown; it can be readily distinguished from all
      species of the P. myersi Group that inhabit the highlands of the Ecuadorian Andes
      by the unique combination of the following characters: body small (adult male SVL
      14.9-19.7 mm; females unknown); dorsal skin shagreen, with a barely visible
      middorsal raphe, scapular and dorsolateral folds; tympanum small but well
      defined; upper eyelid with one enlarged tubercle; males with prominent vocal
      slits, but without nuptial pads on thumbs; fold-like tarsal tubercles. With this
      new species, the number of Pristimantis assigned to the P. myersi Group raises to
      16, of which, 12 are in Ecuador. We provide notes on morphology and color
      variation, advertisement call, and natural history of the new species. 

PMID- 24871829
TI  - State of knowledge of the Acotylea (Polycladida, Platyhelminthes) from the
      Mediterranean coasts of Spain: new records and new species.
AB  - Along the Mediterranean coast of the Iberian Peninsula, great species diversity
      is thought to exist, but our knowledge of Iberian polyclads is, in fact, very
      limited. This study contributes to the Polycladida (Platyhelminthes) of the
      Iberian Peninsula, in particular those of the Mediterranean coast. Nine species,
      mainly new species or new records, are described. Imogine stellae sp. nov. from
      Mar Menor (Murcia, Spain) is described, while I. mediterranea Galleni, 1976 is
      recorded for the first time in Spain. The genus Planocera Blainville, 1828 within
      the Mediterranean basin is reviewed: Planocera graffi Lang, 1879 is redescribed,
      and its synonymisation with Planocera pellucida (Mertens, 1833) considered. Also,
      the genus Notoplanella Bock, 1931 is represented by two species in Spain, N.
      inarmata Bock, 1931 type species, from Formentera Island and N. estelae sp. nov.,
      from Mar Menor. Trigonoporus cephalophtalmus Lang, 1884 is rediscovered after the
      description of Lang (1884). Stylochus neapolitanus (Delle Chiaje, 1841-1844)
      Lang, 1884 is recorded and S. pilidium (Goette, 1881) is also redescribed, and
      Leptoplana mediterranea (Bock, 1913) is newly recorded for the Iberian Peninsula.

PMID- 24871830
TI  - New host records for European Acroceridae (Diptera), with discussion of species
      limits of Acrocera orbiculus (Fabricius) based on DNA-barcoding.
AB  - New European host records for the Acroceridae species Acrocera orbiculus
      (Fabricius) and Ogcodes reginae Trojan are reported. Acrocera orbiculus was
      reared from Amaurobius erberi (Keyserling), and O. reginae from Clubiona
      leucaspis (Simon) and Evarcha jucunda (Lucas). Where possible, DNA-barcodes are
      presented for reared endoparasitoids and their host specimens. Based on
      mitochondrial COI, the intraspecific genetic variability of 15 western
      Palaearctic A. orbiculus is discussed. Maximum likelihood analysis reveals two
      clades, though they have low statistical support and no distinct barcoding gap.
      Therefore, we consider all barcoded specimens of A. orbiculus to be a single
      biological species with a high degree of phenotypic plasticity regarding body
      size and coloration. Based on molecular and morphological evidence, Paracrocera
      kaszabi Majer, Paracrocera manevali Seguy and Paracrocera minuscula Seguy are
      placed in synonymy with A. orbiculus. The male of the Canary Islands endemic
      Acrocera cabrerae Frey is described for the first time.  

PMID- 24871831
TI  - A new record and a new species of the genus Agistemus Summers (Acari:
      Stigmaeidae) from Greece.
AB  - The genus Agistemus Summers (Acari: Stigmaeidae) is reported for the first time
      in Greece. Agistemus duzgunesae Koc, Cobanoglu & Madanlar, a new record for the
      Greek fauna, is re-described and illustrated based on specimens collected from
      various plants. Furthermore, Agistemus macrosetosus Stathakis & Kapaxidi n. sp.
      is described and illustrated based on specimens collected on Rubus sp. A list of
      all species of the genus Agistemus is provided.  

PMID- 24871833
TI  - First record of the brown marmorated stink bug, Halyomorpha halys (Hemiptera:
      Heteroptera: Pentatomidae), in Hungary, with description of the genitalia of both
      sexes.
AB  - The brown marmorated stink bug, Halyomorpha halys (Stal, 1855) (Hemiptera:
      Heteroptera: Pentatomidae) is recorded for the first time from Hungary. The
      circumstances of finding this species and a detailed description of both male and
      female genitalia are given. The currently known distribution, biology and
      significance of the species are briefly reviewed. 

PMID- 24871832
TI  - Phylogeny and taxonomy of Petroschmidtia teraoi (Katayama, 1943) (Osteichthyes:
      Perciformes: Zoarcidae).
AB  - A morphological and genetic reassessment of the phylogeny and taxonomy of the
      dwarf zoarcid fish Lycodes teraoi Katayama, 1943 indicated that the species, a
      senior synonym of Lycodes sadoensis Toyoshima & Honma, 1980, should be placed in
      the genus Petroschmidtia. A redescription of P. teraoi is provided, with remarks
      on its taxonomy. Numerous specimens revealed a wide distribution of P. teraoi in
      the Sea of Japan, as well as in the southern Sea of Okhotsk. 

PMID- 24871834
TI  - The Ulidiini (Diptera: Tephritoidea: Ulidiidae) of Israel, with a key to the
      world species of Ulidia and description of five new species.
AB  - The Ulidiini (Ulidiidae: Ulidiinae) fauna of Israel is reviewed. Eighteen species
      in three genera (Physiphora, Timia and Ulidia) are recognized. Five species are
      described as new: Timia fallax n. sp., T. ritae n. sp., Ulidia aurata n. sp., U.
      hirsuta n. sp. and U. wasimi n. sp. The remaining species are redescribed and all
      species are illustrated. Keys for the identification of the local Physiphora and
      Timia species and of the world species of Ulidia are provided. 

PMID- 24871835
TI  - Four new species of Alebroides Matsumura (Hemiptera: Cicadellidae: Typhlocybinae)
      from China .
AB  - Four new species of the empoascine leafhopper genus Alebroides Matsumura are
      reported from China: A. strumae Yu & Yang, sp. nov., A. chiasmaticus Yu & Yang,
      sp. nov., A. serrulatus Yu & Yang, sp. nov. and A. spanner Yu & Yang, sp. nov. A
      list of all Chinese species of the genus is provided. 

PMID- 24871836
TI  - Beyond Moa's Ark and Wallace's Line: extralimital distribution of new species of
      Austronothrus (Acari, Oribatida, Crotoniidae) and the endemicity of the New
      Zealand oribatid mite fauna.
AB  - The genus Austronothrus was previously known from three species recorded only
      from New Zealand. Austronothrus kinabalu sp. nov. is described from Sabah, Borneo
      and A. rostralis sp. nov. from Norfolk Island, south-west Pacific. A key to
      Austronothrus is included. These new species extend the distribution of
      Austronothrus beyond New Zealand and confirms that the subfamily Crotoniinae is
      not confined to former Gondwanan landmasses. The distribution pattern of
      Austronothrus spp., combining Oriental and Gondwanan localities, is indicative of
      a curved, linear track; consistent with the accretion of island arcs and volcanic
      terranes around the plate margins of the Pacific Ocean, with older taxa
      persisting on younger island though localised dispersal within island arc
      metapopulations. Phylogenetic analysis and an area cladogram are consistent with
      a broad ancestral distribution of Austronothrus in the Oriental region and on
      Gondwanan terranes, with subsequent divergence and distribution southward from
      the Sunda region to New Zealand. This pattern is more complex than might be
      expected if the New Zealand oribatid fauna was derived from dispersal following
      re-emergence of land after inundation during the Oligocene (25 mya), as well as
      if the fauna emanated from endemic, relictual taxa following separation of New
      Zealand from Gondwana during the Cretaceous (80 mya). 

PMID- 24871837
TI  - Sattleria revisited: unexpected cryptic diversity on the Balkan Peninsula and in
      the south-eastern Alps (Lepidoptera: Gelechiidae).
AB  - The taxonomy of Sattleria Povolny from the high mountain systems on the Balkan
      Peninsula and the adjacent parts of the Alps (south-eastern Alps, Dinaric Alps,
      Rila Mountains) is revised based on recently collected material and re-examined
      museum vouchers. Adult morphology and molecular data of the COI barcode region
      support the existence of six strictly allopatric species in this area, including
      four new species: Sattleria sophiae Timossi, sp. nov. (Parco Paneveggio-Pale di
      San Martino, Dolomites, Prov. Trento, Italy), Sattleria dolomitica Huemer, sp.
      nov. (Eastern Dolomites, Prov. South Tyrol, Italy), Sattleria dinarica Huemer,
      sp. nov. (Durmitor NP, Dinaric Alps, Montenegro) and Sattleria haemusi Huemer,
      sp. nov. (Rila Mts., Bulgaria; Sar Planina, Macedonia).  

PMID- 24871838
TI  - Annotated checklist of the diplura (Hexapoda: Entognatha) of California.
AB  - The first checklist of California dipluran taxa is presented with annotations.
      New state and county records are reported, as well as new taxa in the process of
      being described. California has a remarkable dipluran fauna with about 8% of
      global richness. California hosts 63 species in 5 families, with 51 of those
      species endemic to the State, and half of these endemics limited to single
      locales. The genera Nanojapyx, Hecajapyx, and Holjapyx are all primarily
      restricted to California. Two species are understood to be exotic, and six
      dubious taxa are removed from the State checklist. Counties in the central
      Coastal Ranges have the highest diversity of diplurans; this may indicate
      sampling bias. Caves and mines harbor unique and endemic dipluran species, and
      subterranean habitats should be better inventoried. Only four California taxa
      exhibit obvious troglomorphy and may be true cave obligates. In general, the
      North American dipluran fauna is still under-inventoried. Since many taxa are
      morphologically uniform but genetically diverse, genetic analyses should be
      incorporated into future taxonomic descriptions. Natural Heritage Program
      conservation status ranks were recommended.  

PMID- 24871839
TI  - The ascidian-associated mysid Corellamysis eltanina gen.nov., sp.nov. (Mysida,
      Mysidae, Heteromysinae): a new symbiotic relationship from the Southern Ocean.
AB  - A new mysid species representing a new genus is described based on specimens
      collected in the 1968 cruise of the U.S. Navy Ship Eltanin from the Macquarie
      Island region (Southern Ocean). The new mysid, Corellamysis eltanina, is
      characterized by the globular eyes lacking definite eyestalks, the seven and
      eighth thoracic endopods specialized as gnathopods forming a strong subchela, and
      by the armature and shape of the uropod endopod and telson. Corellamysis eltanina
      lives only in the branchial sacs of the ascidian Corella brewinae suggesting an
      obligate endocommensal symbiotic association. Therefore, this is the first known
      report of a mysid living symbiotically with a benthic tunicate, as well as the
      first report of a mysid symbiosis from the Southern Ocean. The distribution and
      habitats of known symbiont mysids are reviewed. An update of identification key
      to world genera and subgenera of Heteromysinae is suggested.  

PMID- 24871840
TI  - Review of Oxystigma Selys with the synonymy of Oxystigma williamsoni Geijskes
      (Odonata: Heteragrionidae).
AB  - Oxystigma williamsoni Geijskes, 1976 is synonymized with Oxystigma petiolatum
      (Selys, 1862), based on a reexamination of an extensive series of both taxa
      identified by D. Geijskes in the RMNH. Illustrations of the variability for both
      taxa and illustrations, maps, and keys for all species are provided. 

PMID- 24871841
TI  - A new Fenestrulina (Bryozoa, Cheilostomata) commensal with tube-dwelling anemones
      (Cnidaria, Ceriantharia) in the tropical southwestern Atlantic.
AB  - A new species of cheilostome bryozoan, Fenestrulina commensalis n. sp., was
      collected in December 2008 by scuba at 5-10 meters depth at Guaibura Beach,
      Guarapari, Espirito Santo state, southeastern Brazil. The specimen was found
      associated with tubes of the cerianthid Pachycerianthus sp., representing the
      first commensal association between a bryozoan and a tube-dwelling anemone.
      Fenestrulina commensalis n. sp. is the third species of the genus found in
      Brazilian waters; it is distinguished from other Atlantic species of Fenestrulina
      by its small angular orificial condyles, a single oral spine and basal anchoring
      rhizoids arising from abfrontal pore chambers. Morphological adaptations to
      encrust the tubes of cerianthids include anchoring rootlets and weakly contiguous
      zooids. These morphological features allow the colony the flexibility to grow
      around the tube and feed relatively undisturbed by silt and detritus, being
      raised well above the soft-sediment substratum in which the tube-anemone grows. 

PMID- 24871842
TI  - The larvae of Stenophylax mitis McLachlan 1875 and Allogamus hilaris (McLachlan
      1876a) (Trichoptera: Limnephilidae), with notes on ecology and zoogeography.
AB  - The paper gives a description of the hitherto unknown larvae of Stenophylax mitis
      McLachlan 1875 and Allogamus hilaris (McLachlan 1876a) (Trichoptera:
      Limnephilidae: Limnephilini; Vshivkova et al. 2007). Information on the
      morphology of the larvae is given and the most important diagnostic features are
      illustrated. In the context of published keys, the larva of Stenophylax mitis
      keys together with Stenophylax permistus McLachlan 1895, S. vibex (Curtis 1834),
      Stenophylax crossotus McLachlan 1884, Platyphylax frauenfeldi (Brauer, in Brauer
      & Low 1857), Micropterna lateralis (Stephens 1837) and M. sequax McLachlan 1875.
      These species are easily separated by a combination of the following features:
      spatial extent of the head spinule areas, setation on femora and on the 9th
      abdominal dorsum, and on the number of posterior sclerites behind each lateral
      protuberance. Allogamus hilaris keys with Allogamus uncatus (Brauer, in Brauer &
      Low 1857), A. mendax (McLachlan 1876a) and Alpopsyche ucenorum (McLachlan 1876b).
      These species are very similar except in head width which is < 1.50 mm in A.
      mendax and A. ucenorum and > 1.61 mm in A. hilaris and A. uncatus; the two
      species in each of the pairs are not separable. With respect to distribution, S.
      mitis ranges from the Iberian Peninsula to the Balkan Peninsula and from southern
      Italy and Greece to the Central European Highlands. Allogamus hilaris is
      restricted to the Western Alps and the northern half of the Apennine Peninsula.
      In addition, ecological characteristics are briefly discussed.  

PMID- 24871843
TI  - Pempheris bexillon, a new species of sweeper (Teleostei: Pempheridae) from the
      Western Indian Ocean.
AB  - Pempheris bexillon new species is described from the 129 mm SL holotype and 11
      paratypes (119-141 mm SL) from the Comoro Islands. Twelve other specimens have
      been examined from the Agalega Islands, Mascarene Islands, and Bassas da India
      (Madagascar). It is differentiated from other Pempheris by the following
      combination of characters: a yellow dorsal fin with a black, distal margin along
      its full length, broadest on anterior rays (pupil-diameter width) and gradually
      narrowing posteriorly, the last ray with only a black tip; large, deciduous
      cycloid scales on the flank; dark, oblong spot on the pectoral-fin base; anal fin
      with a dark margin; segmented anal-fin rays 38-45 (usually >40); lateral-line
      scales 56-65; and total gill rakers on the first arch 31-35; iris reddish-brown.
      Tables of standard meristic and color data for type material of all nominal
      species of cycloid-scaled Pempheris in the Indo-Pacific are provided. 

PMID- 24871844
TI  - Suggestions to improve the Taxonomy Index (T-Index) introduced by Valdecasas
      (2011).

PMID- 24871845
TI  - The immatures of lauxaniid flies (Diptera: Lauxaniidae) and their taxonomical
      implications.
AB  - The immature stages of insects can provide valuable data both for taxonomy and
      phylogeny, but they are well known only for negligible proportion of the
      described species. Here we describe lauxaniid immatures for 17 species that were
      reared under laboratory conditions and subjected to morphological investigation.
      Following species were included in our study: Cnemacantha muscaria, Homoneura
      biumbrata, Homoneura limnea, Minettia austriaca, Minettia fasciata, Minettia
      flaviventris, Minettia loewi, Minettia plumicornis, Peplomyza litura,
      Poecilolycia vittata, Pseudolyciella pallidiventris, Sapromyza apicalis,
      Sapromyza hyalinata, Sapromyza intonsa, Sapromyza sexpunctata, Sapromyzosoma
      quadripunctata, Sapromyzosoma quadricincta. SEM images of the eggs are provided
      along with the illustrations of the cephaloskeleton and brief description of all
      three larval instars. The cephaloskeleton, as well as external morphology suggest
      that subgenus Minettia s. str. may not be monophyletic. Species Sapromyza
      sexpunctata and Sapromyzosoma spp., Pseudolyciella pallidiventris and
      Poecilolycia. vittata are probably closely related. Sapromyza apicalis, S.
      hyalinata and possibly also S. intonsa form a separate clade from the previous
      group. These results clearly support the long-standing suspicion, that genus
      Sapromyza is not monophyletic. Sapromyza sexpunctata should be considered a
      separate genus related to Sapromyzosoma. The spines on dorsal surface of labial
      lobe suggest relationships between Peplomyza and Meiosimyza species. Affinities
      of Cnemacantha muscaria remain uncertain. However, the extended Malpighian
      tubules suggest relationship to Homoneura or Minettia. 

PMID- 24871846
TI  - Descriptions of three new species of Marcusenius Gill, 1862 (Teleostei:
      Mormyridae) from South Africa and Mozambique.
AB  - Morphological and genetic studies of mormyrid fishes belonging to the genus
      Marcusenius from South Africa and Mozambique revealed four species of which three
      are described as new. Marcusenius pongolensis is widespread throughout the
      Incomati, Pongola and Kosi river systems, and sparsely represented in the Limpopo
      River system in South Africa. Marcusenius krameri sp. nov. is endemic to the
      Limpopo River system, and is the sister taxon of M. caudisquamatus sp. nov. from
      the Nseleni and Mhlatuze river systems in the KwaZulu-Natal Province of South
      Africa. The Ruvuma specimens were well differentiated from all southern and
      eastern African species of Marcusenius, and are therefore recognised as M.
      lucombesi sp. nov. Phylogenetic analysis of the mitochondrial cytochrome b gene
      showed that the three new species and M. altisambesi form a monophyletic lineage
      that is sister to a group containing M. pongolensis and M. macrolepidotus.
      Marcusenius krameri and M. lucombesi seems to prefer slow flowing reaches of
      rivers, whereas M. pongolensis and M. caudisquamatus seems to mainly inhabit
      rapid flowing sections of rivers with a rocky substrate. A key to the southern
      African species of Marcusenius is provided. 

PMID- 24871847
TI  - First occurrence of the non-native bryozoan Schizoporella japonica Ortmann (1890)
      in Western Europe.
AB  - Schizoporella japonica Ortmann was described from Japan but was subsequently
      introduced on Pacific oysters to the Pacific coast of North America, where it is
      now well established. In this paper we record it for the first time in European
      waters. The initial discovery was in a marina at Holyhead, North Wales, in July
      2010 but S. japonica has since been observed abundantly in the Orkney Islands
      (from May 2011) and, subsequently, at other localities in northern Scotland.
      Introduction seems most likely to have been on an ocean-going vessel. The British
      material is here fully described and illustrated with SEMs and colour
      photographs; some unusual characters are discussed. Unlike other recently
      introduced bryozoans, S. japonica is a cold-water species and its breeding season
      in Britain extends through the winter. Extensive confusion between this and other
      species of Schizoporella on the west coast of Canada and the USA led us to make
      thorough morphometric comparisons between the species concerned (Schizoporella
      unicornis (Johnston in Wood), Schizoporella errata (Waters) and Schizoporella
      pseudoerrata Soule, Soule and Chaney). Zooid size in cheilostomate bryozoans is
      variable and often an unreliable character for species separation but shape (and
      therefore ratios between variables, which are independent of size) are often
      valuable: S. japonica zooids have a much greater length:width ratio than the
      other species. Density of frontal pseudopores provides a useful discriminatory
      character. Schizoporella unicornis, repeatedly reported in error from the Pacific
      coast of North America, does not occur there; it is a European species. Full
      comparisons are made between S. japonica and S. unicornis for European
      identification and between S. japonica, S. errata and S. pseudoerrata (which are
      also illustrated) for North American localities. 

PMID- 24871849
TI  - Bees of the Colletes flavicornis-group from China with description of one new
      species (Hymenoptera: Apoidea: Colletidae).
AB  - Two species of the Colletes flavicornis-group from China are treated in this
      paper. C. vestitus sp. n. from Xinjiang is illustrated and described, and C.
      popovi Noskiewicz, 1936 is illustrated and redescribed. Both sexes of the two
      species are in addition characterized by DNA barcodes. The type specimens of the
      new species are deposited in the Insect Collection of Institute of Zoology,
      Chinese Academy of Sciences, Beijing, China. 

PMID- 24871848
TI  - Systematics of the genus Heterolaophonte (Crustacea, Copepoda, Harpacticoida),
      with redescription of H. uncinata and H. curvata.
AB  - Both sexes of Heterolaophonte uncinata (Cherniavski, 1868) and H. curvata (Douwe,
      1929) are redescribed based on newly collected material from the Black Sea and
      Mediterranean coasts of Turkey in view of the fact that there has been no
      detailed redescription since their original descriptions. Neotypes are also
      designated for both species. Detailed comparisons of the characters displayed
      among Heterolaophonte Lang, 1948 species reveal that the genus cannot be defined
      by any unique apomorphy. We propose that the structure of the male appendages,
      especially the swimming legs, can provide a considerable number of significant
      characters that are valuable both for taxonomic identification and phylogenetic
      inferences. In addition, several mistakes leading to a great confusion in the
      accurate interpretation of the relationships among species within Heterolaophonte
      are discovered in earlier species descriptions. Therefore, H. rottenburgi (T.
      Scott, 1912), H. exigua (T. Scott, 1912), H. australis (T. Scott, 1912), and H.
      insignis (T. Scott, 1914) are removed from the genus and placed as incertae sedis
      in Laophontidae. We also conclude that H. phycobates (Monard, 1935), H. pygmaea
      (T. Scott, 1893), H. tupitskyi Chislenko, 1976, and H. curvata micarthros Marcus
      & Por, 1960, which still need further taxonomic investigation, have doubtful
      identity within the genus, and we place them as species inquirendae. 

PMID- 24871850
TI  - New species and distribution records of selenopid spiders of the genus Hovops
      Benoit in Madagascar (Araneae, Selenopidae).
AB  - Hovops Benoit is a heterogeneous genus of selenopid spiders that was prior to
      this study represented by seven species that are endemic to Madagascar. Here, we
      describe four new species: H. antakarana sp. n. (?), H. ikongo sp. n. (?), H.
      menabe sp. n. (?), and H. vezo sp. n. (?). A map of the new species is provided
      as well as new records on two of the known species H. pusillus (Simon, 1897) and
      H. legrasi (Simon, 1887). 

PMID- 24871851
TI  - A new species of Pheles Herrich-Schaeffer from Northeast Brazil (Lepidoptera,
      Riodinidae).
AB  - A new species of Riodinidae, Pheles caatingensis Callaghan & Nobre, sp. nov. from
      Ceara and Pernambuco State in Brazil is described, along with its habitat,
      behavior and taxonomic differences with other members of the genus Pheles. Notes
      are included on distribution and mimetic relationships with other sympatric
      insects. 

PMID- 24871852
TI  - A new species of Anastrepha (Diptera: Tephritidae) from Euphorbia tehuacana
      (Euphorbiaceae) in Mexico.
AB  - Anastrepha tehuacana, a new species of Tephritidae (Diptera) from Tehuacan,
      Puebla, Mexico reared from seeds of Euphorbia tehuacana (Brandegee) V.W. Steinm.
      (Euphorbiaceae), is described and illustrated. Its probable relationship to A.
      relicta Hernandez-Ortiz is discussed. 

PMID- 24871853
TI  - A contribution to Macrolasia Weise (Coleoptera: Coccinellidae: Epilachnini).
AB  - A detailed morphological re-description of the Indian genus Macrolasia Weise,
      1903 is given. First drawings of genitalia, SEMs and color photographs are
      included. A distribution map of the genus Macrolasia is provided. A lectotype of
      Macrolasia arcula Weise is designated. 

PMID- 24871854
TI  - Three new species of the genus Austrophthiracarus from New Zealand (Acari:
      Oribatida: Phthiracaridae).
AB  - Three new species of Austrophthiracarus (Oribatida: Phthiracaridae) from New
      Zealand are described: Austrophthiracarus matuku sp. nov. from the Bethells
      Matuku Reserve, Auckland, Austrophthiracarus notoporosus sp. nov. from the Tutoko
      Bench, Fiordland and Austrophthiracarus karioi sp. nov. from the Mt. Karioi,
      Waikato. Holotype specimens are deposited in the New Zealand Arthropod
      Collection, Landcare Research and paratypes are deposited in the Northeast
      Institute of Geography and Agroecology, Chinese Academy of Sciences. 

PMID- 24871855
TI  - Taxonomic validity and phylogenetic relationships of a newly-described tooth
      carp, Aphanius mesopotamicus Coad, 2009 (Teleostei: Cyprinodontidae).
AB  - Variation among complete cytb sequences (1140 bp) of Aphanius mesopotamicus Coad,
      2009 was compared with closely related species, to investigate the validity of
      this taxon as a newly-described tooth-carp based on morphological
      characteristics. Maximum likelihood and Bayesian likelihood trees supported the
      monophyly of A. mesopotamicus and its sister group relationship to A. sophiae.
      Some 10-16 differences were found when compared to four different population
      samples of A. sophiae, whereas, intraspecific differences were only up to 6 bp.
      These distances suggest divergence from a common ancestor with A. sophiae at
      roughly 1 million years ago. These results are congruent with morphology-based
      hypotheses, indicating a recent speciation event. 

PMID- 24871856
TI  - miR-182 attenuates atrophy-related gene expression by targeting FoxO3 in skeletal
      muscle.
AB  - Skeletal muscle atrophy occurs in response to a variety of conditions including
      chronic kidney disease, diabetes, cancer, and elevated glucocorticoids. MicroRNAs
      (miR) may play a role in the wasting process. Activation of the forkhead box O3
      (FoxO3) transcription factor causes skeletal muscle atrophy in patients, animals,
      and cultured cells by increasing the expression of components of the ubiquitin
      proteasome and autophagy-lysosome proteolytic systems. To identify microRNAs that
      potentially modulate the atrophy process, an in silico target analysis was
      performed and miR-182 was predicted to target FoxO3 mRNA. Using a combination of
      immunoblot analysis, quantitative real-time RT-PCR, and FoxO3 3'-UTR luciferase
      reporter genes, miR-182 was confirmed to regulate FoxO3 expression in C2C12
      myotubes. Transfection of miR-182 into muscle cells decreased FoxO3 mRNA 30% and
      FoxO3 protein 67% (P < 0.05) and also prevented a glucocorticoid-induced
      upregulation of multiple FoxO3 gene targets including MAFbx/atrogin-1, autophagy
      related protein 12 (ATG12), cathepsin L, and microtubule-associated protein light
      chain 3 (LC3). Treatment of C2C12 myotubes with dexamethasone (Dex) (1 MUM, 6 h)
      to induce muscle atrophy decreased miR-182 expression by 63% (P < 0.05).
      Similarly, miR-182 was decreased 44% (P < 0.05) in the gastrocnemius muscle of
      rats injected with streptozotocin to induce diabetes compared with controls.
      Finally, miR-182 was present in exosomes isolated from the media of C2C12
      myotubes and Dex increased its abundance. These data identify miR-182 as an
      important regulator of FoxO3 expression that participates in the control of
      atrophy-inducing genes during catabolic diseases. 

PMID- 24871859
TI  - Comparative Evaluation of Dynamic Abdominal Sonography for Hernia and Computed
      Tomography for Characterization of Incisional Hernia.
AB  - IMPORTANCE: Previous work has demonstrated that dynamic abdominal sonography for
      hernia (DASH) is accurate for the diagnosis of incisional hernia. The usefulness
      of DASH for characterization of incisional hernia is unknown. OBJECTIVE: To
      determine whether DASH can be objectively used to characterize incisional hernias
      by measurement of mean surface area (MSA). DESIGN, SETTING, AND PARTICIPANTS: A
      prospective cohort study was conducted. A total of 109 adults with incisional
      hernia were enrolled between July 1, 2010, and March 1, 2012. Patients with a
      stoma, fistula, or soft-tissue infection were excluded. INTERVENTIONS: DASH was
      performed by a surgeon to determine the maximal transverse and craniocaudal
      dimensions of the incisional hernia. A separate surgeon, blinded to the DASH
      results, performed the same measurements using computed tomography (CT). MAIN
      OUTCOMES AND MEASURES: The MSA was calculated, and the difference in MSA by DASH
      and CT was compared using the Wilcoxon signed rank test. Subset analysis was
      performed with patients stratified into nonobese, obese, and morbidly obese
      groups. We hypothesized that there was no significant difference between MSA as
      measured by DASH compared with CT. RESULTS: A total of 109 patients were enrolled
      (mean age, 56 years; mean body mass index, 32.2 [calculated as weight in
      kilograms divided by height in meters squared]; and 67.0% women). The mean (SD)
      MSA measurements were similar between the modalities: DASH, 41.8 (67.5) cm2 and
      CT, 44.6 (78.4) cm2 (P = .82). The MSA measurements determined by DASH and CT
      were also similar for all groups when stratified by body mass index. There were
      15 patients who had a hernia 10 cm or larger in transverse dimension. The mean
      body mass index of this group was 39.2, and the MSA measurements by DASH and CT
      were similar (P = .26). CONCLUSIONS AND RELEVANCE: DASH can be used to
      objectively characterize hernias by MSA, with accuracy demonstrated in the obese
      population and in patients whose hernias were very large (>=10 cm in diameter).
      DASH offers the advantages of real-time imaging and no ionizing radiation and may
      obviate the need for the patient to schedule additional imaging appointments.

PMID- 24871860
TI  - Intracellular gold nanoparticle aggregation and their potential applications in
      photodynamic therapy.
AB  - Gold nanoparticles (Au NPs) with opposite surface charge can form aggregates
      through electrostatic interaction and exhibit surface plasmon resonance (SPR)
      induced-localized electromagnetic (EM) field enhancement under light irradiation.
      Intracellular aggregation of Au NPs can further improve the therapeutic
      efficiency of Au NP-enhanced photodynamic therapy of cancer by promoting singlet
      oxygen generation. 

PMID- 24871857
TI  - Calcium-sensing receptor 20 years later.
AB  - The calcium-sensing receptor (CaSR) has played an important role as a target in
      the treatment of a variety of disease states over the past 20 plus years. In this
      review, we give an overview of the receptor at the cellular level and then
      provide details as to how this receptor has been targeted to modulate cellular
      ion transport mechanisms. As a member of the G protein-coupled receptor (GPCR)
      family, it has a high degree of homology with a variety of other members in this
      class, which could explain why this receptor has been identified in so many
      different tissues throughout the body. This diversity of locations sets it apart
      from other members of the family and may explain how the receptor interacts with
      so many different organ systems in the body to modulate the physiology and
      pathophysiology. The receptor is unique in that it has two large exofacial lobes
      that sit in the extracellular environment and sense changes in a wide variety of
      environmental cues including salinity, pH, amino acid concentration, and
      polyamines to name just a few. It is for this reason that there has been a great
      deal of research associated with normal receptor physiology over the past 20
      years. With the ongoing research, in more recent years a focus on the
      pathophysiology has emerged and the effects of receptor mutations on cellular and
      organ physiology have been identified. We hope that this review will enhance and
      update the knowledge about the importance of this receptor and stimulate future
      potential investigations focused around this receptor in cellular, organ, and
      systemic physiology and pathophysiology.

PMID- 24871861
TI  - Paradigm change in the treatment of non-melanoma skin cancer of the auricle:
      reconstruction with full thickness skin grafting instead of wedge excision.
AB  - Non-melanoma skin cancer (NMSC) has become an epidemic disease and is
      predominantly located in the head and neck area. While historically auricular
      NMSCs are treated by means of a wedge excision, we describe a more elegant
      technique with excellent esthetical results. We conducted a retrospective cohort
      study of 43 consecutive patients with NMSC of the auricle who underwent
      reconstruction with a full thickness skin graft (FTSG). All grafts survived. Two
      patients (5%) showed crust formation, but fully recovered. One patient had an
      irradical resection for which he required a limited re-excision. All patients
      showed excellent esthetical results. When treating NMSC of the auricle,
      reconstruction with a FTSG demonstrates several important advantages. It is a
      relatively simple but oncological safe technique; it leads to excellent
      esthetical and functional outcomes, and shows high patient and surgeon
      satisfaction.

PMID- 24871858
TI  - Identification of a common Wnt-associated genetic signature across multiple cell
      types in pulmonary arterial hypertension.
AB  - Understanding differences in gene expression that increase risk for pulmonary
      arterial hypertension (PAH) is essential to understanding the molecular basis for
      disease. Previous studies on patient samples were limited by end-stage disease
      effects or by use of nonadherent cells, which are not ideal to model vascular
      cells in vivo. These studies addressed the hypothesis that pathological processes
      associated with PAH may be identified via a genetic signature common across
      multiple cell types. Expression array experiments were initially conducted to
      analyze cell types at different stages of vascular differentiation (mesenchymal
      stromal and endothelial) derived from PAH patient-specific induced pluripotent
      stem (iPS) cells. Molecular pathways that were altered in the PAH cell lines were
      then compared with those in fibroblasts from 21 patients, including those with
      idiopathic and heritable PAH. Wnt was identified as a target pathway and was
      validated in vitro using primary patient mesenchymal and endothelial cells. Taken
      together, our data suggest that the molecular lesions that cause PAH are present
      in all cell types evaluated, regardless of origin, and that stimulation of the
      Wnt signaling pathway was a common molecular defect in both heritable and
      idiopathic PAH. 

PMID- 24871862
TI  - Multilocular sinonasal malignant melanoma: a poor prognostic subgroup?
AB  - Clinical observations show that two subtypes of sinonasal malignant melanoma
      exist: uni- and multilocular melanoma. The aim of this retrospective study was to
      determine the prevalence and outcome of multilocular sinonasal malignant
      melanoma. All patients with sinonasal malignant melanoma treated at our
      institution between 1992 and 2011 were included. Survival and recurrence data
      were analyzed related to the distribution pattern of the tumors and other
      factors. Twenty-five patients were identified and included in the analysis. Seven
      patients (28 %) suffered from multilocular, the remaining 18 patients (72 %) from
      unilocular sinonasal malignant melanoma. The first group showed a significantly
      worse disease-free survival, whereas disease-specific and overall survival did
      not differ between the two subtypes. Multilocular sinonasal malignant melanoma is
      associated with an unfavorable disease-free survival compared to its unilocular
      counterpart.

PMID- 24871864
TI  - A fluorescence lifetime-based binding assay for acetylpolyamine amidohydrolases
      from Pseudomonas aeruginosa using a [1,3]dioxolo[4,5-f][1,3]benzodioxole (DBD)
      ligand probe.
AB  - High-throughput assays for drug screening applications have to fulfill particular
      specifications. Besides the capability to identify even compounds with low
      potency, one of the major issues is to minimize the number of false-positive hits
      in a screening campaign in order to reduce the logistic effort for the subsequent
      cherry picking and confirmation procedure. In this respect, fluorescence lifetime
      (FLT) appears as an ideal readout parameter that is supposed to be robust against
      autofluorescent and light-absorbing compounds, the most common source of
      systematic false positives. The extraordinary fluorescence features of the
      recently discovered [1,3]dioxolo[4,5-f][1,3] benzodioxole dyes were exploited to
      develop an FLT-based binding assay with exceptionally robust readout. The assay
      setup was comprehensively validated and shown to comply not only with all
      requirements for a powerful high-throughput screening assay but also to be
      suitable to determine accurate binding constants for inhibitors against enzymes
      of the histone deacetylase family. Using the described binding assay, the first
      inhibitors against three members of this enzyme family from Pseudomonas
      aeruginosa were identified. The compounds were characterized in terms of potency
      and selectivity profile. The novel ligand probe should also be applicable to
      other homologues of the histone deacetylase family that are inhibited by N
      hydroxy-N'-phenyloctandiamide. 

PMID- 24871863
TI  - Long-term trends in gender, T-stage, subsite and treatment for laryngeal cancer
      at a single center.
AB  - To investigate the changes in the epidemiology of laryngeal squamous cell
      carcinoma (LSCC) regarding gender, T-stage and subsite distribution, and to
      identify the potential effect of introducing new therapeutic alternatives for
      early and advanced stage LSCC. A prospective cohort study of LSCC patients
      diagnosed and treated at a single tertiary referral center in Norway.
      Retrospective analysis of prospectively recorded data from 1,616 patients treated
      for LSCC in all subsites of the larynx during 1983-2010. Females represented an
      increasing proportion of cases throughout the study (p < 0.01) and presented more
      often than men with supraglottic cancer (p < 0.01). Marked changes in the
      distribution of T-stages over time were observed in both early and advanced stage
      LSCC. T1a glottic tumors constituted 56 % of all early-stage LSCC and were
      predominantly treated by transoral endoscopic laser surgery. The introduction of
      chemoradiotherapy for advanced stage LSCC offers a distinct advantage for
      laryngeal preservation. The increasing proportion of females with LSCC may be
      explained by changes in smoking habits. The proportion of T1a glottic LSCC
      gradually increased over time, while T4 supraglottic LSCC became less frequent.
      Videostroboscopy should be considered mandatory in the diagnosis and follow-up of
      LSCC. Transoral laser microsurgery is the standard first-line treatment for T1a
      glottic tumors. Chemoradiotherapy has reduced the number of total laryngectomies
      and is now regarded as the primary treatment for advanced stage tumors.

PMID- 24871865
TI  - Cold vapor generation of Zn based on dielectric barrier discharge induced plasma
      chemical process for the determination of water samples by atomic fluorescence
      spectrometry.
AB  - A new plasma chemical vapor generation (plasma-CVG) method for Zn was developed
      by dielectric barrier discharge (DBD). The dissolved Zn ions was readily
      converted to volatile species by DBD plasma in the presence of hydrogen and then,
      the generated Zn vapor, Zn(0), was detected by cold vapor atomic fluorescence
      spectrometry (AFS). It eliminated the use of unstable tetrahydroborate-reducing
      reagent and high-purity acids. The operating conditions for the DBD plasma-CVG
      system were optimized for the efficient vapor generation of Zn. In addition,
      possible interferences from coexisting ions on the plasma-CVG of Zn were also
      examined. No appreciable matrix interference was found from most of the examined
      ions at concentration of 1 mg L(-1). However, severe depression of the Zn vapor
      generation efficiency was observed in the presence of ions at 10 mg L(-1). Under
      the optimal conditions, the limit of detection (LOD) was calculated to be 0.2 MUg
      L(-1); good repeatability (relative standard deviation (RSD) = 2.6%, n = 11) was
      obtained for a 20 Zn MUg L(-1) standard. The accuracy of the proposed method was
      validated though analysis of Zn in reference material of simulated natural water
      sample GSB07-1184-2000 and the determined result was in good agreement with the
      reference value. The proposed method has also been successfully applied to the
      determination of Zn in Changjiang River water, Wuhan East Lake water, and Wuhan
      tap water samples. It provides an alternative green vapor generation method for
      Zn.

PMID- 24871866
TI  - Radix natalensis: the effect of Fasciola hepatica infection on the reproductive
      activity of the snail.
AB  - Experimental infections of Egyptian Radix natalensis (shell height at miracidial
      exposure: 4 mm) with a French isolate of Fasciola hepatica were carried out under
      laboratory conditions at 22  degrees C to specify the characteristics and follow
      the dynamics of their egg-laying. Controls constituted unexposed R. natalensis of
      the same size. No significant difference between controls and the uninfected
      snails of the exposed group was noted, whatever the parameter considered. In
      controls and exposed snails, the dates of the first egg masses were close to each
      other (56.4-65.3 days). In contrast, the life span of snails and the length of
      the egg-laying period were significantly shorter and egg production was
      significantly lower in infected R. natalensis than in controls and uninfected
      snails. In infected R. natalensis, but without cercarial shedding (NCS snails),
      egg production was irregular throughout the egg-laying period. In cercarial
      shedding (CS) snails, the first egg masses were laid before the first cercarial
      emergence (at a mean of 56 days and 67 days, respectively). Thereafter, egg mass
      production of CS snails was irregular up to day 72 of the experiment, stopped
      during the following two weeks and started again after day 88 for a single snail.
      In conclusion, the F. hepatica infection of R. natalensis reduced the
      reproductive activity in both NCS and CS snails. The pattern noted for egg
      production in infected R. natalensis seems to be species-specific because of the
      high shell size of this lymnaeid and its role as an atypical intermediate host in
      the life cycle of the parasite.

PMID- 24871867
TI  - Beyond the dichotomy: six religious views of homosexuality.
AB  - Using published theological and scholarly evidence, this article disrupts the
      stereotypical "born gay"/"sinful choice" dichotomy widely assumed to characterize
      religious views of homosexuality in the United States. It argues that we need to
      keep moral questions separate from questions about the fixity or fluidity of
      sexual orientation. Rather than two, American Christian and Jewish views of
      homosexuality can been seen on a range from the "God Hates Fags" view through
      "Love the Sinner, Hate the Sin," "We Don't Talk About That," "They Can't Help
      It," "God's Good Gift," and a queer-theological view of the "Godly Calling." 

PMID- 24871868
TI  - Stable isotope dilution gas chromatography-mass spectrometry for quantification
      of thymoquinone in black cumin seed oil.
AB  - Black cumin seed (Nigella sativa L.) is a widely used spice and herb, where
      thymoquinone (2-isopropyl-5-methyl-1,4-benzoquinone) is the major bioactive
      compound. Here, a stable isotope dilution (SID) gas chromatography-mass
      spectrometry (GC-MS) technique was developed for the quantification of
      thymoquinone. A doubly deuterated thymoquinone ([(2)H2]-thymoquinone) was
      synthesized for the first time with more than 93% deuteration degree shown by
      mass spectrometry and proton nuclear magnetic resonance ((1)H NMR). This compound
      was used as an internal standard for the quantification of thymoquinone using a
      SID GC-MS method. The validation experiment showed a recovery rate of 99.1 +/-
      1.1% relative standard deviation (RSD). Standard addition and external
      calibration methods have also been used to quantify thymoquinone, which cross
      validated the developed stable isotope dilution assay (SIDA). In comparison to
      external calibration and standard addition methods, the SIDA method is robust and
      accurate. The concentration of thymoquinone in five marketed black cumin seed
      oils ranged between 3.34 and 10.8 mg/mL by use of SID GC-MS. 

PMID- 24871870
TI  - Preferences for daily or intermittent pre-exposure prophylaxis regimens and
      ability to anticipate sex among HIV uninfected members of Kenyan HIV
      serodiscordant couples.
AB  - Intermittent dosing for pre-exposure prophylaxis (PrEP) has been proposed as an
      alternative to daily PrEP to reduce cost and patient drug exposure and to improve
      adherence. One possible dosing regimen is pre-intercourse PrEP, which requires
      anticipating sex in advance. We examined preferences for daily versus pre
      intercourse PrEP and ability to anticipate sex among 310 HIV uninfected members
      of HIV serodiscordant heterosexual couples in Thika, Kenya, with high HIV
      knowledge and experience with daily PrEP use in a clinical trial setting.
      Preferences were evenly split between daily PrEP (47.4 %) and pre-intercourse
      PrEP (50.7 %). Participants were more likely to prefer daily PrEP if they
      reported unprotected sex during the prior month (adjusted prevalence ratio [aPR]
      1.48, 95 % CI 1.20-1.81) or <80 % adherence to study drug (aPR 1.50, 95 % CI 1.25
      1.79), and were less likely to prefer daily PrEP if sex was usually planned,
      versus spontaneous (aPR 0.76, 95 % CI 0.61-0.96). A minority (24.2 %) reported
      anticipating sex >3 h in advance, with younger participants being less likely to
      do so (aPR 0.43, 95 % CI 0.23-0.83 for ages 18-29 vs. >=40). Findings suggest
      that intermittent PrEP could be a popular option in this population, but that
      optimal adherence and sufficient drug levels might be challenging with a pre
      intercourse regimen. 

PMID- 24871871
TI  - Anaesthetic conserving device AnaConDa: dead space effect and significance for
      lung protective ventilation.
AB  - BACKGROUND: The anaesthetic conserving device AnaConDa (ACD) reflects exhaled
      anaesthetic agents thereby facilitating the use of inhaled anaesthetic agents
      outside operating theatres. Expired CO2 is, however, also reflected causing a
      dead space effect in excess of the ACD internal volume. CO2 reflection from the
      ACD is attenuated by humidity. This study tests the hypothesis that sevoflurane
      further attenuates reflection of CO2. An analysis of clinical implications of our
      findings was performed. METHODS: Twelve postoperative patients received
      mechanical ventilation using a conventional heat and moisture exchanger (HME,
      internal volume 50 ml) and an ACD (100 ml), the latter with or without
      administration of sevoflurane. The ACD was also studied with a test lung at high
      sevoflurane concentrations. Reflection of CO2 and dead space effects were
      evaluated with the single-breath test for CO2. RESULTS: Sevoflurane reduced but
      did not abolish CO2 reflection. In patients, the mean dead space effect with 0.8%
      sevoflurane was 88 ml larger using the ACD compared with the HME (P<0.001), of
      which 38 ml was due to CO2 reflection. Our calculations show that with the use of
      the ACD, normocapnia cannot be achieved with tidal volume <6 ml kg(-1) even when
      respiratory rate is increased. CONCLUSIONS: An ACD causes a dead space effect
      larger than its internal volume due to reflection of CO2, which is attenuated but
      not abolished by sevoflurane administration. CO2 reflection from the ACD limits
      its use with low tidal volume ventilation, such as with lung protection
      ventilation strategies. CLINICAL TRIAL REGISTRATION: Clinical Trials NCT01699802.

PMID- 24871872
TI  - Accuracy of impedance cardiography for evaluating trends in cardiac output: a
      comparison with oesophageal Doppler.
AB  - BACKGROUND: Impedance cardiography (ICG) enables continuous, beat-by-beat, non
      invasive, operator-independent, and inexpensive cardiac output (CO) monitoring.
      We compared CO values and variations obtained by ICG (NiccomoTM, Medis) and
      oesophageal Doppler monitoring (ODM) (CardioQTM, Deltex Medical) in surgical
      patients. METHODS: This prospective, observational, single-centre study included
      32 subjects undergoing surgery with general anaesthesia. CO was measured
      simultaneously with ICG and ODM before and after events likely to modify CO
      (vasopressor administration and volume expansion). One hundred and twenty pairs
      of CO measurements and 94 pairs of CO variation measurements were recorded.
      RESULTS: The CO variations measured by ICG correlated with those measured by ODM
      [r=0.88 (0.82-0.94), P<0.001]. Trending ability was good for a four-quadrant plot
      analysis with exclusion of the central zone (<10%) [95% confidence interval (CI)
      for concordance (0.86; 1.00)]. Moderate to good trending ability was observed
      with a polar plot analysis (angular bias: -7.2 degrees ; 95% CI -12.3 degrees ; 
      2.5 degrees ; with radial limits of agreement -38 degrees ; 24 degrees ). After
      excluding subjects with chronic obstructive pulmonary disease, a Bland-Altman
      plot showed a mean bias of 0.47 litre min(-1), limits of agreements between -1.24
      and 2.11 litre min(-1), and a percentage error of 35%. CONCLUSION: ICG appears to
      be a reliable method for the non-invasive monitoring of CO in patients undergoing
      general surgery.

PMID- 24871873
TI  - Fibrinogen but not factor XIII deficiency is associated with bleeding after
      craniotomy.
AB  - BACKGROUND: Postoperative haemorrhage in neurosurgery is associated with
      significant morbidity and mortality. There is controversy whether or not factor
      XIII (FXIII) deficiency leads to bleeding complications after craniotomy.
      Decreased fibrinogen levels have been associated with an increased incidence of
      bleeding complications in cardiac and orthopaedic surgery. The aim of this study
      was to assess perioperative fibrinogen and FXIII levels in patients undergoing
      elective intracranial surgery with and without severe bleeding events. METHODS:
      Perioperative FXIII and fibrinogen levels were prospectively assessed in 290
      patients undergoing elective craniotomy. Patients were divided into two groups
      according to the presence or absence of severe bleeding requiring surgical
      revision. Coagulation test results of these groups were compared using Student's
      t-test. RESULTS: The incidence of postoperative severe bleeding was 2.4%. No
      differences in FXIII levels were observed, but postoperative fibrinogen levels
      were significantly lower in patients suffering from postoperative haematoma
      compared with those without postoperative intracranial bleeding complications
      [237 mg dl(-1) (standard deviation, SD 86) vs 170 mg dl(-1) (SD 35), P=0.03]. The
      odds ratio for postoperative haematoma in patients with a postoperative
      fibrinogen level below 200 mg dl(-1) was 10.02 (confidence interval: 1.19-84.40,
      P=0.03). CONCLUSIONS: This study emphasizes the role of fibrinogen as potentially
      modifiable risk factor for perioperative bleeding in intracranial surgery. Future
      randomized controlled trials will be essential to identify patients who might
      benefit from fibrinogen substitution during neurosurgical procedures.

PMID- 24871875
TI  - Late-life cynical distrust, risk of incident dementia, and mortality in a
      population-based cohort.
AB  - OBJECTIVE: We investigated the association between late-life cynical distrust and
      incident dementia and mortality (mean follow-up times of 8.4 and 10.4 years,
      respectively) in the Cardiovascular Risk Factors, Aging and Dementia Study.
      METHODS: Cynical distrust was measured based on the Cook-Medley Scale and
      categorized into tertiles. Cognitive status was evaluated with a 3-step protocol
      including screening, clinical phase, and differential diagnostic phase. Dementia
      was diagnosed according to DSM-IV criteria. Complete data on exposure, outcome,
      and confounders were available from 622 persons (46 dementia cases) for the
      dementia analyses and from 1,146 persons (361 deaths) for the mortality analyses.
      Age, sex, systolic blood pressure, total cholesterol, fasting glucose, body mass
      index, socioeconomic background, smoking, alcohol use, self-reported health, and
      APOE genotype were considered as confounders. RESULTS: Cynical distrust was not
      associated with dementia in the crude analyses, but those with the highest level
      of cynical distrust had higher risk of dementia after adjusting for confounders
      (relative risk 3.13; 95% confidence interval [CI] 1.15-8.55). Higher cynical
      distrust was associated with higher mortality in the crude analyses (hazard ratio
      1.40; 95% CI 1.05-1.87) but the association was explained by confounders
      (adjusted hazard ratio 1.19; 95% CI 0.86-1.61). CONCLUSIONS: Higher cynical
      distrust in late life was associated with higher mortality, but this association
      was explained by socioeconomic position, lifestyle, and health status.
      Association between cynical distrust and incident dementia became evident when
      confounders were considered. This novel finding suggests that both psychosocial
      and lifestyle-related risk factors may be modifiable targets for interventions.
      We acknowledge the need for larger replication studies.

PMID- 24871874
TI  - Defining the clinical course of multiple sclerosis: the 2013 revisions.
AB  - Accurate clinical course descriptions (phenotypes) of multiple sclerosis (MS) are
      important for communication, prognostication, design and recruitment of clinical
      trials, and treatment decision-making. Standardized descriptions published in
      1996 based on a survey of international MS experts provided purely clinical
      phenotypes based on data and consensus at that time, but imaging and biological
      correlates were lacking. Increased understanding of MS and its pathology, coupled
      with general concern that the original descriptors may not adequately reflect
      more recently identified clinical aspects of the disease, prompted a re
      examination of MS disease phenotypes by the International Advisory Committee on
      Clinical Trials of MS. While imaging and biological markers that might provide
      objective criteria for separating clinical phenotypes are lacking, we propose
      refined descriptors that include consideration of disease activity (based on
      clinical relapse rate and imaging findings) and disease progression. Strategies
      for future research to better define phenotypes are also outlined. 

PMID- 24871876
TI  - Results of uncemented hemiarthroplasty as primary treatment of severe proximal
      humerus fractures in the elderly.
AB  - OBJECTIVES: The purpose of this study was to analyze functional and radiologic
      results of a consecutive series of elderly patients who underwent uncemented
      hemiarthroplasty as primary treatment of complex proximal humeral fractures.
      METHODS: Twenty-one patients with severe proximal humerus fracture (three or four
      fragments and three- or four-fragment fracture dislocations) were treated with
      uncemented proximal humerus hemiarthroplasty. Patients were evaluated using the
      Constant-Murley Score, the Quick scale Disabilities of Arm, Shoulder and Hand
      (Quick-DASH) Score, range of motion, residual pain, radiographic parameters, and
      complications including clinical and radiologic data of mobilization. RESULTS:
      After a mean postoperative period of 20.57 months (range 12-42 months), the mean
      Constant-Murley Score was 44 points (20-57), the mean Quick-DASH score was 24
      points (16-39), postoperative pain according to a mean visual analogue scale was
      1 (0-8), active abduction was 50 degrees  (30-135), and active flexion 70 degrees
      (20-120). There were no cases of infection, deep vein thrombosis, dislocation,
      blood transfusions, or reoperation because of prosthetic loosening. Bivariate
      analysis of demographic data, radiologic findings, and other variables showed
      associations between duration of surgery and a higher Quick-DASH score (0.606; p
      = 0.037), and the number of sessions of rehabilitation with a higher Quick-DASH
      score (0.708; p = 0.015). CONCLUSIONS: The results of treatment of severe
      proximal humerus fractures in the elderly with an uncemented hemiarthroplasty are
      safe and promising; however, a comparative cohort study (cemented vs. uncemented)
      and long-term follow-up are still needed.

PMID- 24871877
TI  - Dynamics of Besnoitia besnoiti infection in cattle.
AB  - Bovine besnoitiosis is caused by the cyst-forming apicomplexan parasite Besnoitia
      besnoiti. This disease progresses in two sequential phases: a febrile acute phase
      with oedemas and respiratory disorders, and a chronic phase characterized by the
      presence of subcutaneous tissue cysts and skin lesions. Serious consequences of
      the infection are poor body condition, sterility in bulls and eventual death. The
      role of host/parasite-dependent factors, which play a major role in the
      pathogenesis of the disease, is not yet fully elucidated. Isolate/strain
      virulence, parasite stage, dose and the route of parasite inoculation were
      studied under different experimental conditions, which make it difficult to
      compare the results. Data on host-dependent factors obtained from naturally
      infected cattle showed that (i) the seroprevalence of infection is similar in
      both sexes; (ii) seropositivity increases with age; (iii) both beef and dairy
      cattle are susceptible to the infection; and (iv) the cell-mediated immune
      response is likely to play a major role because a T cell response has been
      observed around several tissue cysts. Whether colostral antibodies are protective
      and to what extent the humoral immune response might reflect the
      disease/protection status require further research. Thus, a well-established
      experimental bovine model could help to clarify these important questions. The
      dynamics of B. besnoiti infection in cattle and available knowledge on relevant
      factors in the pathogenesis of the infection are reviewed in the present work.

PMID- 24871878
TI  - Upconversion nanophosphor: an efficient phosphopeptides-recognizing matrix and
      luminescence resonance energy transfer donor for robust detection of protein
      kinase activity.
AB  - Protein kinases play important regulatory roles in intracellular signal
      transduction pathways. The aberrant activities of protein kinases are closely
      associated with the development of various diseases, which necessitates the
      development of practical and sensitive assays for monitoring protein kinase
      activities as well as for screening of potential kinase-targeted drugs. We
      demonstrate here a robust luminescence resonance energy transfer (LRET)-based
      protein kinase assay by using NaYF4:Yb,Er, one of the most efficient upconversion
      nanophosphors (UCNPs), as an autofluorescence-free LRET donor and a
      tetramethylrhodamine (TAMRA)-labeled substrate peptide as the acceptor.
      Fascinatingly, besides acting as the LRET donor, NaYF4:Yb,Er UCNPs also serve as
      the phosphopeptide-recognizing matrix because the intrinsic rare earth ions of
      UCNPs can specifically capture the fluorescent phosphopeptides catalyzed by
      protein kinases over the unphosphorylated ones. Therefore, a sensitive and
      generic protein kinase assay is developed in an extremely simple mix-and-read
      format without any requirement of surface modification, substrate immobilization,
      separation, or washing steps, showing great potential in protein kinases-related
      clinical diagnosis and drug discovery. To the best of our knowledge, this is the
      first report by use of rare earth-doped UCNPs as both the phospho-recognizing and
      signal reporting elements for protein kinase analysis. 

PMID- 24871879
TI  - [Historical causalities, things and chances].

PMID- 24871880
TI  - [Causality and history. Introduction to the German debates in the 18th century].

PMID- 24871881
TI  - ["Secret causes": causality and determinism in the classical age].
AB  - The notion of the "secret cause", which appears in many classical texts is tied
      to a particular practice of science and a conception of its methods where the
      "law" finds itself at the center of the nexus. If certain phenomena appear to
      escape the law, one is obliged to amend the law through the introduction of a
      series of "small equations." If the calculation of probabilities is deployed,
      this is to precisely reveal causes which are, at their origin, secret, but which
      will gradually become less so and eventually conform to laws. 

PMID- 24871882
TI  - [The historian's competence tested by authority: on an academic debate of the
      18th century].
AB  - The debate which took place in the 1720s at the Royal Academy of Inscriptions and
      Letters on the possibility or impossibility of understanding the history of the
      first centuries of Rome is generally interpreted to be less of a debate than an
      important epistemological clarification. A contextualization which takes into
      account the political stakes of the debate allows one to understand that the
      debate was the beginning of a larger process of the autonomisation of the field
      of historical studies, not only from the perspective of disciplinary divides, but
      also in relation to monarchal power. 

PMID- 24871883
TI  - [Historical causality and relative contemporaneity Einsteinian relativity in the
      historical sciences].
AB  - The construction of historical frame of reference based on the distinction
      between and articulation of phenomenological and chronological times. As it
      relativises the notion of simultaneity and inverts its relation to causality, the
      special theory of relativity can induce analogous modes of reflection on the
      themes of "contemporaneity" in the history of art (Panofsky) and in epistemology
      (Bachelard). This "relativist" method, often misunderstood, sheds light on both
      historical and presentist methods. 

PMID- 24871884
TI  - ["The end justifies the means." Historical realism and causality in modernity].
AB  - Perceived all along, from the beginning of the modern era, causality in history
      cannot be abstracted from a reflection on "the reason and uses of States". Such
      realism engages with the heart of the arts of governance, the practices which
      form the basis for the adage "the end justifies the means". In order to assess
      the implications of this maxim on the definition of causality, this article
      examines the modalities of the description of historical facts, its usages and
      censoring (understood as a necessary means to aspired ends), and the calculation
      of the aleatory dimensions of politics. 

PMID- 24871885
TI  - [Discussion points from the days of "history and causality." Augusta library,
      Wolfenbuttel, May 2009].

PMID- 24871886
TI  - [The concept of racial democracy in Brazilian intellectual history].
AB  - This article aims to reconstruct the history of the term "racial democracy" in
      Brazilian sociological literature. This term, usually associated with the idea of
      "myth", is used in many studies of race relations without little definition or
      clarity. This article retraces its origins, in particular by showing that the
      concept is not the invention of Gilberto Freyre. It then examines the evolution
      of its use with particular emphasis on Unesco's research in the 1950s and the
      texts of Florestan Fernandes in the 1960s. 

PMID- 24871888
TI  - Prognosis and prognostic factors of differentiated thyroid carcinoma after the
      appearance of metastasis refractory to radioactive iodine therapy.
AB  - Differentiated thyroid carcinomas (DTCs) are generally indolent, but few
      therapeutic strategies are available after a metastatic recurrence that is
      refractory to radioactive iodine (RAI) therapy. Molecular-target therapy has
      shown promising results for DTCs with RAI-refractory recurrence. However, not all
      RAI-refractory recurrences are progressive, and even those that are progressive
      may not be immediately life-threatening. Here we investigated the prognosis and
      prognostic factors of 74 DTC patients (52 females, 22 males) in whom RAI
      refractory metastases appeared. The five-year and 10-year cause-specific survival
      (CSS) rates of the 74 patients (8-82 yrs of age; median age at the detection of
      metastases, 61 yrs) were 95% and 70%, respectively, and the older patients (>= 60
      yrs, n=38) and male patients were significantly more likely to die of carcinoma.
      Also in multivariate analysis, older age (>= 60 years) and male gender were
      independent predictors of carcinoma-related death. Taken together, our data
      indicate that RAI-refractory metastases of older patients and male patients are
      more progressive than those of other patients. Further studies are necessary to
      clarify the appropriate indications for molecular-target therapy for RAI
      refractory and progressive metastases. 

PMID- 24871889
TI  - Atomistic modeling of strain-controlled cyclic loading in TiAl crystalline
      nanowire.
AB  - In this paper, atomistic modeling of L10-TiAl nanowire has been performed
      utilizing the Embedded Atom Method (EAM) potential under strain-controlled cyclic
      loading. A nanowire oriented along the <100> axis with a cross-sectional
      dimension (D) of ~80 A with a Length-to-width (L/D) ratio of 10.0 has been
      considered. Strain-controlled cyclic loading at room temperature has been
      performed by oscillating the nanowire length dimension sinusoidal with a specific
      amplitude and period. Tension-compression cyclic loading was employed with zero
      mean strain. Cyclic loading with percentage strains (%epsilon) of one to five
      percent have been considered. It has been observed that the cyclic stress in the
      nanowire continues to fluctuate during the initial loading cycles. However, once
      the nanowire becomes stable, a smooth variation of stresses with varying strain
      has been observed. The cause of initial fluctuations in the nanowire has been
      studied by varying (a) the amount of load (strain) applied, (b) the nanowire
      structure during cyclic loading, and (c) the rate at which the load has been
      applied. It has been identified that the rate of loading could be used for
      controlling the initial fluctuations of nanowire. Finally, a method for the
      calculation of cyclic stress versus cyclic strain for nanowires has been
      proposed. A cyclic stress versus cyclic strain curve has been plotted for a given
      L/D = 10 and a period of 10 ps. Results show that the TiAl nanowire is having 3/2
      times higher stiffness in tension as compared to compression at a given strain
      under cyclic loading.

PMID- 24871890
TI  - Untargeted lipidomic analysis in chronic obstructive pulmonary disease.
      Uncovering sphingolipids.
AB  - RATIONALE: Cigarette smoke is the major risk factor in the development of chronic
      obstructive pulmonary disease (COPD). Lipidomics is a novel and emerging research
      field that may provide new insights in the origins of chronic inflammatory
      diseases, such as COPD. OBJECTIVES: To investigate whether expression of the
      sputum lipidome is affected by COPD or cigarette smoking. METHODS: Lipid
      expression was investigated with liquid chromatography and high-resolution
      quadrupole time-of-flight mass spectrometry in induced sputum comparing smokers
      with and without COPD, and never-smokers. Changes in lipid expression after 2
      month smoking cessation were investigated in smokers with and without COPD.
      MEASUREMENTS AND MAIN RESULTS: More than 1,500 lipid compounds were identified in
      sputum. The class of sphingolipids was significantly higher expressed in smokers
      with COPD than in smokers without COPD. At single compound level, 168
      sphingolipids, 36 phosphatidylethanolamine lipids, and 5 tobacco-related
      compounds were significantly higher expressed in smokers with COPD compared with
      smokers without COPD. The 13 lipids with a high fold change between smokers with
      and without COPD showed high correlations with lower lung function and
      inflammation in sputum. Twenty (glyco)sphingolipids and six tobacco-related
      compounds were higher expressed in smokers without COPD compared with never
      smokers. Two-month smoking cessation reduced expression of 26 sphingolipids in
      smokers with and without COPD. CONCLUSIONS: Expression of lipids from the
      sphingolipid pathway is higher in smokers with COPD compared with smokers without
      COPD. Considering their potential biologic properties, they may play a role in
      the pathogenesis of COPD.

PMID- 24871891
TI  - Impact of research participation on parents of seriously ill children.
AB  - BACKGROUND: There is a paucity of research evidence to guide health care
      providers' practice in pediatric palliative care. At the same time, some
      clinicians and Institutional Review Boards are reluctant to approve such studies
      because of concerns about further burdening families. Yet, there is some evidence
      that research participation can have positive effects for families. OBJECTIVE: To
      obtain parents' perceptions about their experience of participating in one of two
      research studies. DESIGN: Descriptive, quantitative survey. SETTING/SUBJECTS:
      Caregivers of children with life-threatening conditions (n=323) who were caring
      for the child at home. MEASUREMENTS: Researcher-designed Impact of Participation
      questionnaire. RESULTS: Few differences between the two groups were found on
      Impact responses. Not a single parent reported regretting participating in their
      study and almost all (96.3%) reported that conducting research about family's
      experiences in pediatric palliative care had value. Just over three-quarters
      (76.2%) did not find participation at all painful, and 73.7% reported that
      participation was about as painful as expected, with 23.2% reporting less
      painful. Approximately half (50.5%) said that participation had at least some
      positive effect and only three parents reported any negative effect. An
      overwhelming majority (93.4%) would recommend participation to other parents in a
      similar situation. CONCLUSIONS: Participation in research for families with
      children who have a life-threatening condition is not only acceptable to parents,
      but may in fact have a positive effect. Although clinicians and Institutional
      Review Boards may be hesitant to fully support such research, it is clear that
      conducting research in the field of pediatric palliative care is important.

PMID- 24871897
TI  - Learning and memory: Neurogenesis erases existing memories.

PMID- 24871896
TI  - The role of genetic variants in genes regulating the oxytocin-vasopressin
      neurohumoral system in childhood-onset aggression.
AB  - OBJECTIVE: The genetic etiology of aggressive behaviors remains elusive, but
      growing evidence suggests that they are heritable, and certain genetic variants
      have been implicated as contributing factors. The oxytocin-vasopressin (OXT-AVP)
      neurohumoral system has recently been implicated in social behaviors. Oxytocin,
      especially, has been linked to prosocial behaviors such as trust and social
      bonds. Hence, the aim of this study was to determine whether genes regulating
      this system were also associated with childhood-onset aggressive behaviors.
      METHODS: Our sample included 182 White children showing extreme, persistent, and
      pervasive aggressive behavior. These cases were matched with 182 White controls
      on the basis of sex and age. We used PCR to determine the genotype for 28 single
      nucleotide polymorphisms within eight genes regulating the OXT-AVP system,
      including CD38 polymorphisms. Genotypic analyses were carried out using STATA,
      whereas differences in haplotypic and allelic frequencies were analyzed using
      Unphased. RESULTS: None of the results reached significance after correction for
      multiple testing. However, nominally significant allelic effects were observed
      for OXTR rs6770632T (P=0.028) and AVPR1A rs11174811G (P=0.040) in females, and
      OXTR rs237898A (P=0.006), rs237902C (P=0.007), and AVP rs3761249A (P=0.008) in
      males. CONCLUSION: Genetic variants regulating the OXT-AVP system may be
      associated with childhood-onset aggression.

PMID- 24871898
TI  - Sleep: Inducing lucid dreams.

PMID- 24871899
TI  - Further studies on ethyl 5-hydroxy-indole-3-carboxylate scaffold: design,
      synthesis and evaluation of 2-phenylthiomethyl-indole derivatives as efficient
      inhibitors of human 5-lipoxygenase.
AB  - 5-Lipoxygenase (5-LO), an enzyme that catalyzes the initial steps in the
      biosynthesis of pro-inflammatory leukotrienes, is an attractive drug target for
      the pharmacotherapy of inflammatory and allergic diseases. Here, we present the
      design, synthesis and biological evaluation of novel series of ethyl 5
      hydroxyindole-3-carboxylate derivatives that efficiently inhibit human 5-LO. SAR
      analysis revealed that the potency of compounds is closely related to the
      positioning of the substituents at the phenylthiomethyl ring. The introduction of
      methyl or chlorine groups in ortho- and ortho/para-position of thiophenol
      represent the most favorable modifications. Among all tested compounds, ethyl 5
      hydroxy-2-(mesitylthiomethyl)-1-methyl-1H-indole-3-carboxylate (19) is the most
      potent derivative which blocks 5-LO activity in cell-free assays with IC50 = 0.7
      MUM, and suppressed 5-LO product synthesis in polymorphonuclear leukocytes with
      IC50 = 0.23 MUM. 

PMID- 24871900
TI  - Design and synthesis of novel indole-chalcone fibrates as lipid lowering agents.
AB  - A series of novel indole-chalcone fibrates were synthesized and their
      hypolipidemic activity was evaluated in triton WR-1339 induced hyperlipidemic rat
      model. Preliminary studies indicated that the hybrids 19, 24 and 29 exhibited
      potent in vitro antioxidant and significant in vivo antidyslipidemic effects. Our
      results suggest that these new hybrid architectures may serve as promising leads
      for the development of next generation lipid lowering agents. 

PMID- 24871901
TI  - Non-linear infrared spectroscopy of the water bending mode: direct experimental
      evidence of hydration shell reorganization?
AB  - The structure and dynamics of liquid water are further studied by investigating
      the bend vibrational mode of HDO/D2O and pure H2O via two-dimensional infrared
      spectroscopy (2D-IR) and linear absorption. The experimental findings and
      theoretical calculations support a picture in which the HDO bend is localized and
      the H2O bend is delocalized. The HDO and H2O bends present a loss of the
      frequency-frequency correlation in subpicosecond time scale. While the loss of
      correlation for the H2O bend is likely to be associated with the vibrational
      dynamics of a delocalized transition, the loss of the correlation in the
      localized HDO bend appears to arise from the fluctuations/rearrangements of the
      local environment. Interestingly, analysis of the HDO 2D-IR spectra shows the
      presence of multiple overlapping inhomogeneous distributions of frequencies that
      interchange in a few picoseconds. Theoretical calculations allow us to propose an
      atomistic model of the observed vibrational dynamics in which the different
      inhomogeneous distributions and their interchange are assigned to water molecules
      with different hydrogen-bond states undergoing chemical exchange. The frequency
      shifts as well as the concentration of the water molecules with single and double
      hydrogen-bonds as donors derived from the theory are in good agreement with our
      experimental findings. 

PMID- 24871902
TI  - Low temperature assembly of functional 3D DNA-PNA-protein complexes.
AB  - Proteins have evolved to carry out nearly all the work required of living
      organisms within complex inter- and intracellular environments. However,
      systematically investigating the range of interactions experienced by a protein
      that influence its function remains challenging. DNA nanostructures are emerging
      as a convenient method to arrange a broad range of guest molecules. However,
      flexible methods are needed for arranging proteins in more biologically relevant
      3D geometries under mild conditions that preserve protein function. Here we
      demonstrate how peptide nucleic acid (PNA) can be used to control the assembly of
      cytochrome c (12.5 kDa, pI 10.5) and azurin (13.9 kDa, pI 5.7) proteins into
      separate 3D DNA nanocages, in a process that maintains protein function. Toehold
      mediated DNA strand displacement is introduced as a method to purify PNA-protein
      conjugates. The PNA-proteins were assembled within 2 min at room temperature and
      within 4 min at 11  degrees C, and hybridize with even greater efficiency than
      PNA conjugated to a short peptide. Gel electrophoresis and steady state and time
      resolved fluorescence spectroscopy were used to investigate the effect of protein
      surface charge on its interaction with the negatively charged DNA nanocage. These
      data were used to generate a model of the DNA-PNA-protein complexes that show the
      negatively charged azurin protein repelled away from the DNA nanocage while the
      positively charged cytochrome c protein remains within and closely interacts with
      the DNA nanocage. When conjugated to PNA and incorporated into the DNA nanocage,
      the cytochrome c secondary structure and catalytic activity were maintained, and
      its redox potential was reduced modestly by 20 mV possibly due to neutralization
      of some positive surface charges. This work demonstrates a flexible new approach
      for using 3D nucleic acid (PNA-DNA) nanostructures to control the assembly of
      functional proteins, and facilitates further investigation of protein
      interactions as well as engineer more elaborate 3D protein complexes. 

PMID- 24871903
TI  - Mild fluorination of chloropyridines with in situ generated anhydrous
      tetrabutylammonium fluoride.
AB  - This paper describes the fluorination of nitrogen heterocycles using anhydrous
      NBu4F. Quinoline derivatives as well as a number of 3- and 5-substituted
      pyridines undergo high-yielding fluorination at room temperature using this
      reagent. These results with anhydrous NBu4F compare favorably to traditional
      halex fluorinations using alkali metal fluorides, which generally require
      temperatures of >=100  degrees C. 

PMID- 24871905
TI  - Toward minimum effort reaching trajectories formation in robot-based
      rehabilitation after stroke: an innovative guidance scheme proposition.
AB  - In therapy after stroke, intensive and repetitive training is crucial for
      relearning of motor abilities and functionalities. Besides conventional therapy,
      rehabilitation robotic systems are used in the treatment, where a minimum jerk
      model is used widely in the formation of the point-to-point movement trajectory,
      which is not necessarily the appropriate choice for hemiparetic upper extremity
      training. This paper examines and analyzes the influence of a selected form of a
      flexor muscle tightness on trajectory formation and proposes a guidance scheme
      that yields minimum effort in robot-assisted arm reaching movement. A dynamic
      upper extremity model with the three clinically most relevant muscles that
      develop tightness because of spasticity after stroke was used in the optimization
      study that examined key features of trajectory formation. The results showed that
      the trajectories and their velocity profiles become significantly different in
      the presence of muscle tightness. On the basis of dynamic optimization results,
      we experimentally examined selected trajectories in a selected individual with
      chronic hemiparesis. The experimental results confirmed the importance of
      appropriate selection of reaching trajectories' velocity profiles. The results of
      optimization and experimentation showed the importance of the velocity profile of
      the robot-based guidance scheme, which has an influence on the necessary invested
      'effort' between starting/ending points to overcome muscle tightness. This study
      showed that muscle tightness exerts a significant influence on trajectory
      formation as well as on its velocity profile. The proposed innovative guidance
      scheme might be useful for practical arm reaching robot-supported movement
      training in the clinical environment. We suggested that for each hemiparetic
      patient, the initial identification session before training should experimentally
      determine the 'optimal' parameters for the rehabilitation guidance scheme that
      would optimally match the particular muscle tightness constraints. 

PMID- 24871906
TI  - Palladium catalyzed, heteroatom-guided C-H functionalization in the synthesis of
      substituted isoquinolines and dihydroisoquinolines.
AB  - A new approach for the functionalization of C-4 of isoquinolines is reported. The
      method utilizes palladium catalyzed, hetero-atom guided (or electrophilic
      metalation) direct arylation via regioselective C-H functionalization of
      dihydroisoquinolines. 

PMID- 24871904
TI  - Drug-eluting nasal implants: formulation, characterization, clinical applications
      and challenges.
AB  - Chronic inflammation and infection of the nasal sinuses, also referred to as
      Chronic Rhinosinusitis (CRS), severely affects patients' quality of life.
      Adhesions, ostial stenosis, infection and inflammation relapses complicate
      chronic sinusitis treatment strategies. Drug-eluting stents, packings or implants
      have been suggested as reasonable alternatives for addressing these concerns.
      This article reviewed potential drug candidates for nasal implants, formulation
      methods/optimization and characterization methods. Clinical applications and
      important considerations were also addressed. Clinically-approved implants
      (PropelTM implant, the Relieva stratusTM MicroFlow spacer, and the Sinu-FoamTM
      spacer) for CRS treatment was an important focus. The advantages and limitations,
      as well as future considerations, challenges and the need for additional research
      in the field of nasal drug implant development, were discussed. 

PMID- 24871908
TI  - Arrangement of fibril side chains studied by molecular dynamics and simulated
      infrared and vibrational circular dichroism spectra.
AB  - Highly ordered assemblies of beta-sheet-forming peptide and protein fibrils have
      been the focus of much attention because of their multiple and partially unknown
      biological functions, in particular as related to degenerative neuronal
      disorders. Recently, vibrational circular dichroism (VCD) spectra have been shown
      to provide a unique means of detection for such extended structures utilizing
      modes of the peptide main chain backbone. In the case of poly-glutamic acid,
      surprising VCD responses were also found for side chain modes. In this study, in
      an attempt to explain this latter observation and obtain a link between fibrillar
      structure and its optical spectral properties, molecular dynamics (MD) methods
      are used to model the geometry and dynamics of assemblies containing repeating
      beta-strands of Glu(n). A crystal-like model was adopted for the MD structure
      simulations. Infrared and VCD spectra for segments of MD modeled fibrillar
      geometries were first calculated using density functional theory (DFT), and then,
      those parameters were applied to larger structures by means of Cartesian
      coordinate transfer (CCT) of atomic tensors from the segments. The computations
      suggest the side chains exhibit residual conformational constraints, resulting in
      local coupling giving rise to non-negligible VCD intensity, albeit with an
      overall broad distribution. Calculated spectral distributions are qualitatively
      consistent with the experimental results but do differ in magnitude. The
      possibility of realistic modeling of vibrational spectra significantly broadens
      the potential for application of optical spectroscopies in structural studies of
      these aggregated biopolymers.

PMID- 24871909
TI  - Fluorescent detection of TNT and 4-nitrophenol by BSA Au nanoclusters.
AB  - Rapid and sensitive detection of 2,4,6-trinitrotoluene (TNT) and 4-nitrophenol (4
      NP) has attracted considerable attention due to their wide applications as
      nitroaromatic explosive materials. A novel fluorescence method for TNT and 4-NP
      based on bovine serum albumin functionalized fluorescent gold nanoclusters (BSA
      Au-NCs) has been developed. The detection probe BSA Au-NCs can be used as a
      fluorescent probe for the sensitive and selective detection of TNT and 4-NP
      simultaneously. A good linearity of fluorescence detection using BSA Au-NCs as a
      fluorescent probe was observed for TNT and 4-NP concentrations in the range of
      10(-8)-5 * 10(-5) M and 10(-9)-5 * 10(-5) M, with a detection limit of 10 nM and
      1 nM, respectively. The high specificity of TNT and 4-NP with BSA Au-NCs
      interactions provided excellent selectivity towards detecting TNT and 4-NP over
      other relevant nitroaromatic compounds. This system can be applied to test strips
      to detect TNT and 4-NP with high sensitivity and selectivity. The vapour of TNT
      and 4-NP can be detected using BSA Au-NCs test paper within 1 min with a
      detection limit of 10 pM and 1 pM. 

PMID- 24871907
TI  - The relation of potassium and sodium intakes to diet cost among U.S. adults.
AB  - The 2010 Dietary Guidelines recommended that Americans increase potassium and
      decrease sodium intakes to reduce the burden of hypertension. One reason why so
      few Americans meet the recommended potassium or sodium goals may be perceived or
      actual food costs. This study explored the monetary costs associated with
      potassium and sodium intakes using national food prices and a representative
      sample of US adults. Dietary intake data from the 2001-2002 National Health and
      Nutrition Examination Survey were merged with a national food prices database. In
      a population of 4744 adults, the association between the energy-adjusted sodium
      and potassium intakes, and the sodium-to-potassium ratio (Na:K) and energy
      adjusted diet cost was evaluated. Diets that were more potassium-rich or had
      lower Na:K ratios were associated with higher diet costs, while sodium intakes
      were not related to cost. The difference in diet cost between extreme quintiles
      of potassium intakes was $1.49 (95% confidence interval: 1.29, 1.69). A food
      level analysis showed that beans, potatoes, coffee, milk, bananas, citrus juices
      and carrots are frequently consumed and low-cost sources of potassium. Based on
      existing dietary data and current American eating habits, a potassium-dense diet
      was associated with higher diet costs, while sodium was not. Price interventions
      may be an effective approach to improve potassium intakes and reduce the Na:K
      ratio of the diet. The present methods helped identify some alternative low-cost
      foods that were effective in increasing potassium intakes. The identification and
      promotion of lower-cost foods to help individuals meet targeted dietary
      recommendations could accompany future dietary guidelines. 

PMID- 24871911
TI  - Empowering others.

PMID- 24871912
TI  - Escuchando a Nuestros Jovenes: a latino youth photovoice project on teen
      pregnancy.
AB  - Half of Latina teens in the United States will become pregnant at least once by
      age 20 years. The purpose of this study was to explore a Pacific Northwest
      community's strengths and weaknesses, through photovoice, as viewed by Latino
      youth to understand their concerns related to teen pregnancy. Participants were
      asked to take photographs of what they believe contributes to preventing or
      increasing the risk of teen pregnancy. There were 14 Latino youth, ages 15-20
      years, who enrolled in the study, and 9 completed all aspects of the project
      including public dissemination. The themes were categorized as (a) risks for
      teens, (b) pressure, (c) education is key, (d) community resources, and (e)
      Latino values. Presentations to the community generated dialogue and problem
      solving and laid the groundwork for planning interventions.

PMID- 24871913
TI  - Understanding access to care and health needs of Hispanic women from an urban
      community.
AB  - As a first step in a proposed program of community-based participatory research,
      this study investigated access to care and specific health needs in a population
      of Hispanic women from a medically underserved, urban community. There were 66
      Hispanic women recruited at a local church to complete a 94-item researcher
      developed survey. Thirty-two percent of women in the study were not U.S.
      citizens. Being insured, being a citizen, and having a medical diagnosis were
      significant in satisfaction with care. The most prevalent health issue for this
      population was being overweight or obese. This study demonstrates the use of the
      community needs assessment process in the development of interventions to improve
      a community's health and health care. This is especially true in the Hispanic
      community in which large variations based on culture and country of origin will
      impact the success of planned interventions.

PMID- 24871914
TI  - Pathways to economic opportunity: an overview of innovative career pathway
      collaborations for Latinos into frontline health care occupations.
AB  - Extraordinary Latino population growth has created demand for bilingual and
      culturally competent frontline health care providers to address the "culture gap"
      in health care delivery meeting the linguistic and cultural needs of Latino
      communities (Cohen, Gabriel, & Terrell, 2002). This article reviews career
      pathway programs that serve as workforce development models for Latinos seeking
      opportunity within frontline health care occupations, a sector with high
      projected employment growth in the coming decade. The programs examined reflect
      innovative approaches that target Latino participants for entrance into some of
      these occupations including registered nurses (RNs), licensed practical nurses
      (LPNs), human service assistants, and bachelor's level social worker positions
      that offer low-wage Latinos the possibility of entering a profession where they
      may earn a livable wage. Implications for policy, research, and practice are
      discussed.

PMID- 24871915
TI  - The role of vitamin D in the health of Hispanic adults with diabetes.
AB  - The highest prevalence of low vitamin D levels are among Hispanics and non
      Hispanic Blacks. Evidence suggests that low vitamin D levels may contribute to
      increased risk for diabetes and its complications. Hispanics are at greater risk
      for vitamin D deficiency. To address the relationship between vitamin D,
      diabetes, and Hispanics, this research is described. Evidence supports an
      association between low vitamin D and risk for diabetes, but there remains
      insufficient evidence to suggest whether treatment of low vitamin D can prevent
      or improve diabetes. In addition, there is limited research regarding vitamin D
      deficiency in the Hispanic population. Factors such as obesity, dark skin
      pigmentation, northern geographical latitude, and prevalence of renal
      insufficiency may place Hispanics at greater risk for low vitamin D levels.
      Nurses need to understand the signs and symptoms of vitamin D deficiency and
      treatment recommendation guidelines, which are also described. This information
      will allow nurses to improve the health outcomes and decrease the disparities
      amongst adult Hispanics with diabetes.

PMID- 24871916
TI  - Using telehealth to improve diabetes management in the Hispanic population.

PMID- 24871917
TI  - Synthesis of 1-amino-2-aroyl/acetylnaphthalenes through a base mediated one pot
      inter and intramolecular C-C bond formation strategy.
AB  - A new precursor 2-(1-cyano-2,2-bis(methylthio)vinyl)benzonitrile has been
      synthesized by the reaction of 2-cyanomethylbenzonitrile, carbon disulfide and
      methyl iodide under basic conditions. The reaction of 2-(1-cyano-2,2
      bis(methylthio)vinyl)benzonitrile with various functionalized aryl/heteroaryl
      methyl ketones or acetone under basic conditions afforded 4-amino-3
      aroyl/heteroaroyl/acetyl-2-methylsulfanylnaphthalene-1-carbonitriles in good
      yields through a (5C + 1C) annulation strategy; this involves sequential
      intermolecular, followed by intramolecular, C-C bond formation reactions. The
      structure of the product was confirmed by single crystal X-ray crystallography. 

PMID- 24871919
TI  - Physiological basis of starvation resistance in Drosophila leontia: analysis of
      sexual dimorphism.
AB  - Geographically varying starvation stress has often been considered as a natural
      selector that constrains between-population differences for starvation resistance
      (SR) in Drosophila species. On the Indian subcontinent, a dozen Drosophila
      species have shown clinal variations in SR across latitude, but the evolved
      physiological basis of such contrasting adaptations is largely unknown. In the
      present study, I untangled the physiological basis of sex-specific as well as
      between-population divergence for SR in D. leontia, collected across a
      latitudinal transect of the Indian subcontinent (11 degrees 45'-31 degrees 19'N).
      Secondly, I tested the assumptions that hardening to starvation stress
      facilitates an increased survival under subsequent lethal levels of starvation,
      and such plastic effects differ between the sexes. I observed several interesting
      results. In contrast to a steeper cline of starvation-related traits with
      latitude in females, a shallower gradient was observed for males. Females stored
      higher (~1.3-fold) dry-mass-specific levels of body lipids and glycogen contents,
      and utilized these both of these energy resources under starvation stress,
      whereas the starved males metabolized only body lipids as a source of energy.
      Conversely, the rate of body lipid utilization and threshold need were
      considerably higher in females as compared with males. Between-population
      differences were significant for storage levels of energy reserves only, but not
      for other avenues (rate of metabolite utilization and threshold need) of SR for
      both sexes. These findings indicate that multiple pathways shape the
      physiological basis of sexual dimorphism for SR in D. leontia. Further, single or
      multiple bouts of starvation hardening conferred an increased longevity (~4-9 h;
      P<0.001) under subsequent lethal levels of starvation stress for females only,
      and such plastic responses were consistent with a decrease in rate of metabolite
      utilization. Nevertheless, between-population effects were non-significant for
      absolute hardening capacity (AHC=KSR-C). Altogether, these findings suggest that
      similar evolutionary constraints have resulted in divergent genetic as well as
      plastic responses to evolve adaptations under starvation stress, and account for
      the observed sexual dimorphism for basal SR in D. leontia. 

PMID- 24871918
TI  - Autogrid-based clustering of kinases: selection of representative conformations
      for docking purposes.
AB  - The selection of the most appropriate protein conformation is a crucial aspect in
      molecular docking experiments. In order to reduce the errors arising from the use
      of a single protein conformation, several authors suggest the use of several
      tridimensional structures for the target. However, the selection of the most
      appropriate protein conformations still remains a challenging goal. The protein
      3D-structures selection is mainly performed based on pairwise root-mean-square
      deviation (RMSD) values computation, followed by hierarchical clustering. Herein
      we report an alternative strategy, based on the computation of only two atom
      affinity map for each protein conformation, followed by multivariate analysis and
      hierarchical clustering. This methodology was applied on seven different kinases
      of pharmaceutical interest. The comparison with the classical RMSD-based strategy
      was based on cross-docking of co-crystallized ligands. In the case of epidermal
      growth factor receptor kinase, also the docking performance on 220 known ligands
      were evaluated, followed by 3D-QSAR studies. In all the cases, the herein
      proposed methodology outperformed the RMSD-based one. 

PMID- 24871920
TI  - Scaling of the hydrostatic skeleton in the earthworm Lumbricus terrestris.
AB  - The structural and functional consequences of changes in size or scale have been
      well studied in animals with rigid skeletons, but relatively little is known
      about scale effects in animals with hydrostatic skeletons. We used glycol
      methacrylate histology and microscopy to examine the scaling of mechanically
      important morphological features of the earthworm Lumbricus terrestris over an
      ontogenetic size range from 0.03 to 12.89 g. We found that L. terrestris becomes
      disproportionately longer and thinner as it grows. This increase in the length to
      diameter ratio with size means that, when normalized for mass, adult worms gain
      ~117% mechanical advantage during radial expansion, compared with hatchling
      worms. We also found that the cross-sectional area of the longitudinal
      musculature scales as body mass to the ~0.6 power across segments, which is
      significantly lower than the 0.66 power predicted by isometry. The cross
      sectional area of the circular musculature, however, scales as body mass to the
      ~0.8 power across segments, which is significantly higher than predicted by
      isometry. By modeling the interaction of muscle cross-sectional area and
      mechanical advantage, we calculate that the force output generated during both
      circular and longitudinal muscle contraction scales near isometry. We hypothesize
      that the allometric scaling of earthworms may reflect changes in soil properties
      and burrowing mechanics with size. 

PMID- 24871921
TI  - Non-visual numerical discrimination in a blind cavefish (Phreatichthys
      andruzzii).
AB  - Over a decade of comparative studies, researchers have found that rudimentary
      numerical abilities are widespread among vertebrates. While experiments in
      mammals and birds have employed a variety of stimuli (visual, auditory and
      tactile), all fish studies involved visual stimuli and it is unknown whether fish
      can process numbers in other sensory modalities. To fill this gap, we studied
      numerical abilities in Phreatichthys andruzzii, a blind cave-dwelling species
      that evolved in the phreatic layer of the Somalia desert. Fish were trained to
      receive a food reward to discriminate between two groups of objects placed in
      opposite positions of their home tank. In Experiment 1, subjects learned to
      discriminate between two and six objects, with stimuli not controlled for non
      numerical continuous variables that co-vary with numbers, such as total area
      occupied by stimuli or density. In Experiment 2, the discrimination was two
      versus four, with half of the stimuli controlled for continuous quantities and
      half not controlled for continuous quantities. The subjects discriminated only
      the latter condition, indicating that they spontaneously used non-numerical
      information, as other vertebrates tested in similar experiments. In Experiments 3
      and 4, cavefish trained from the beginning only with stimuli controlled for
      continuous quantities proved able to learn the discrimination of quantities based
      on the sole numerical information. However, their numerical acuity was lower than
      that reported in other teleost fish tested with visual stimuli. 

PMID- 24871922
TI  - Biomechanics of substrate boring by fig wasps.
AB  - Female insects of diverse orders bore into substrates to deposit their eggs. Such
      insects must overcome several biomechanical challenges to successfully oviposit,
      which include the selection of suitable substrates through which the ovipositor
      can penetrate without itself fracturing. In many cases, the insect may also need
      to steer and manipulate the ovipositor within the substrate to deliver eggs at
      desired locations before rapidly retracting her ovipositor to avoid predation. In
      the case of female parasitoid ichneumonid wasps, this process is repeated
      multiple times during her lifetime, thus testing the ability of the
      ovipositioning apparatus to endure fracture and fatigue. What specific
      adaptations does the ovipositioning apparatus of a female ichneumonoid wasp
      possess to withstand these challenges? We addressed this question using a model
      system composed of parasitoid and pollinator fig wasps. First, we show that
      parasitoid ovipositor tips have teeth-like structures, preferentially enriched
      with zinc, unlike the smooth morphology of pollinator ovipositors. We describe
      sensillae present on the parasitoid ovipositor tip that are likely to aid in the
      detection of chemical species and mechanical deformations and sample
      microenvironments within the substrate. Second, using atomic force microscopy, we
      show that parasitoid tip regions have a higher modulus compared with regions
      proximal to the abdomen in parasitoid and pollinator ovipositors. Finally, we use
      videography to film wasps during substrate boring and analyse buckling of the
      ovipositor to estimate the forces required for substrate boring. Together, these
      results allow us to describe the biomechanical principles underlying substrate
      boring in parasitoid ichneumonid wasps. Such studies may be useful for the
      biomimetic design of surgical tools and in the use of novel mechanisms to bore
      through hard substrates. 

PMID- 24871923
TI  - Prior experience with conspecific signals enhances auditory midbrain
      responsiveness to conspecific vocalizations.
AB  - There is a long history in neuroethology of investigating how communication
      signals influence the brain and behavior. It has become increasingly clear that
      brain areas associated with sensory processing are plastic in adults and that
      this plasticity is related to reproductive condition. However, the role of
      communication signal reception in adult auditory plasticity has received
      relatively little attention. Here, we investigated whether the reception of
      communication signals (a frog chorus) could enhance the responsiveness of the
      auditory system to future reception of communication signals (a single male
      call). We found that animals that had been exposed to 10 days of a male chorus
      had stronger auditory midbrain immediate early gene expression than animals that
      had been exposed to 10 days of random tones when tested with 30 min of male calls
      or 30 min of tones. Our results suggest that exposure to dynamic social stimuli,
      like frog choruses, may play an important role in shaping the neural and
      behavioral responses to communication signals. 

PMID- 24871924
TI  - Reducing the histopathological changes of radioiodine to the lacrimal glands by a
      popular anti-oxidant: lycopene.
AB  - PURPOSE OF THE STUDY: Radioiodine (RAI) has been used for the treatment of
      hyperthyroidism and well-differentiated thyroid carcinoma for more than 70 years.
      Lycopene is an anti-oxidant, which is plentiful in red fruits. The purpose of
      this study was to investigate the possible inhibitory effect of lycopene on the
      RAI-induced acute histopathological changes in rat lacrimal glands. METHODS: In
      this experimental animal study, 32 rats were randomly divided into three groups.
      The first group (control group, n = 8) was not given neither (131)I nor lycopene,
      the second group (RAI group, n = 12) was administrated a single dose of 3 mCi
      (131)I and 1 cc physiologic saline by gastric gavage. The third group (lycopene
      group, n = 12) was administrated 3 mCi (131)I and 1 cc lycopene by gastric
      gavage. After 24 h of the last dose, the animals were decapitated on the seventh
      day and their lacrimal glands were removed for histopathological examination.
      RESULTS: The cell shape and the cell size variation and poorly defined
      acidophilic cell outlines in all lacrimal glands were observed significantly less
      frequently in the lycopene group than in the RAI group. CONCLUSIONS: Our
      histopathological examinations have revealed that lycopene prevents rat lacrimal
      glands against RAI-related acute histopathological changes.

PMID- 24871925
TI  - Recent research and future prospects for gemtuzumab ozogamicin: could it make a
      comeback?
AB  - Gemtuzumab ozogamicin (GO), a humanized anti-CD33 monoclonal antibody conjugated
      to calicheamicin, was initially granted accelerated US FDA approval for the
      treatment of acute myeloid leukemia (AML), but was later voluntarily withdrawn
      from the market because of increased toxicity and lack of benefit in a Phase III
      clinical trial. However, subsequently published clinical trials that compared
      standard chemotherapy to chemotherapy plus GO in children and adults with AML
      demonstrated clinical benefit of GO in certain subgroups of patients, leading to
      renewed interest in GO. Although the re-emergence of GO into the clinic is
      uncertain, these results validate the use of CD33 as a target for AML therapy.
      Much research is underway to develop novel anti-CD33 therapeutics that may be
      able to pick up where GO left off. 

PMID- 24871926
TI  - Are all polar molecules hydrophilic? Hydration numbers of nitro compounds and
      nitriles in aqueous solution.
AB  - The hydration numbers of typical aprotic polar substances bearing dipole moments
      larger than 3 D, such as nitro compounds and nitriles, were precisely determined
      in aqueous solution using high frequency dielectric relaxation techniques up to a
      frequency of 50 GHz at 25  degrees C. The hydration number is one of the most
      quantitative parameters for determining the hydrophilicity or hydrophobicity of a
      compound. The hydration numbers of various nitriles, such as acetonitrile,
      propionitrile and n-butyronitrile bearing cyano groups, were determined to be ca.
      0, irrespective of the species of molecule. Moreover, the hydration numbers of
      various nitro compounds, such as nitromethane, nitroethane and 1-nitropropane,
      were also evaluated to be ca. 0. These findings clearly reveal that neither cyano
      nor nitro functional groups form strong hydrogen bonds to water molecules.
      Consequently, neither nitro compounds nor nitriles are hydrophilic, despite their
      high polarities due to their large dipole moments. Rather, these compounds are
      "hydroneutral," with hydrophilicities intermediate between those of hydrophilic
      and hydrophobic molecules. The molecular motions of the examined highly polar
      molecules in aqueous solution were well described with single Debye-type
      rotational relaxation modes without strong interactions between the solute and
      water molecules, but with relatively strong interactions between the polar solute
      molecules due to the Kirkwood factor being less than unity. This small Kirkwood
      factor indicated that both nitro and cyano groups have a tendency to align in an
      anti-parallel intermolecular configuration due to their strong dipole-dipole
      interactions as a result of their dipole moments greater than 3 D. 

PMID- 24871927
TI  - Heterostructures produced from nanosheet-based inks.
AB  - The new paradigm of heterostructures based on two-dimensional (2D) atomic
      crystals has already led to the observation of exciting physical phenomena and
      creation of novel devices. The possibility of combining layers of different 2D
      materials in one stack allows unprecedented control over the electronic and
      optical properties of the resulting material. Still, the current method of
      mechanical transfer of individual 2D crystals, though allowing exceptional
      control over the quality of such structures and interfaces, is not scalable. Here
      we show that such heterostructures can be assembled from chemically exfoliated 2D
      crystals, allowing for low-cost and scalable methods to be used in device
      fabrication. 

PMID- 24871929
TI  - Synthesis and Pharmacological Evaluation of New Chemical Entities from Ibuprofen
      as Novel Analgesic Candidates.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) are the first choice of drugs that
      are normally used for the treatment of pain and inflammation. Ibuprofen (I) and
      its analogues as the most widely used NSAIDs have been synthesized in recent
      years. In an effort to establish new candidates with improved analgesic
      properties, derivatives (II-VII) with substituted aromatic as well as aliphatic
      moieties were synthesized in this experiment and evaluated in formalin test with
      rats. The results were compared to ibuprofen and control groups. Findings
      indicated that derivatives with new alkylphenyl rings (VI and VII) had some
      similar or more analgesic activities relative to the control and ibuprofen
      groups, respectively; which could be justified as to more alkyl and phenyl groups
      instead of p-isobutylphenyl moiety in I. 

PMID- 24871928
TI  - Dynamics and evolution of beta-catenin-dependent Wnt signaling revealed through
      massively parallel clonogenic screening.
AB  - Wnt/beta-catenin signaling is of significant interest due to the roles it plays
      in regulating development, tissue regeneration and disease. Transcriptional
      reporters have been widely employed to study Wnt/beta-catenin signal transduction
      in live cells and whole organisms and have been applied to understanding
      embryonic development, exploring oncogenesis and developing therapeutics.
      Polyclonal heterogeneity in reporter cell lines has historically been seen as a
      challenge to be overcome in the development of novel cell lines and reporter
      based assays, and monoclonal reporter cell lines are commonly employed to reduce
      this variability. A375 cell lines infected with a reporter for Wnt/beta-catenin
      signaling were screened over short (<6) and long (>25) generational timescales.
      To characterize phenotypic divergence over these time-scales, a microfabricated
      cell array-based screen was developed enabling characterization of 1119 clonal
      colonies in parallel. This screen revealed phenotypic divergence after <6
      generations at a similar scale to that observed in monoclonal cell lines cultured
      for >25 generations. Not only were reporter dynamics observed to diverge widely,
      but monoclonal cell lines were observed with seemingly opposite signaling
      phenotypes. Additionally, these observations revealed a generational-dependent
      trend in Wnt signaling in A375 cells that provides insight into the pathway's
      mechanisms of positive feedback and self-inhibition. 

PMID- 24871930
TI  - A prospective research study of anti-glaucoma drugs prescribing, utilization
      pattern and adverse drug reaction recording in a university hospital.
AB  - OBJECTIVE: This study was carried out to evaluate the drug prescribing,
      utilization pattern and adverse drug reactions recording associated with drugs
      prescribed to glaucoma patients. MATERIALS AND METHODS: A total of 50 glaucoma
      patients were included in the study, based on inclusion and exclusion criteria.
      All the observations were recorded in drug utilization and ADR recording
      documentation form. RESULTS: Out of 50 patients suffering from glaucoma, 38
      patients (76%) were diagnosed open angle glaucoma, 4 patients (8%) closed angle
      glaucoma and 8 patients (16%) post-operative respectively. There were 19 patients
      (38%) males and 31 patients (62%) were females. The age range between 41-50 years
      had the maximum number of patients 15 (30%). A total of 17 patients (34%) had
      family history of glaucoma. Timolol was prescribed to 34 patients (68%), followed
      by dorzolamide 18 patients (36%) and acetazolamide 14 patients (28%). A total of
      32 patients (64%) were prescribed single drug therapy whereas 18 patients (36%)
      were on multiple drug therapy. A total of 25 patients (50%) reported ADR. In the
      present study, latanoprost was associated with maximum number of ADRs 9 patients
      (18%) followed by acetazolamide 7 patients (14%), dorzolamide 4 patients (8%),
      then timolol 3 patients (6%) and pilocarpine 2 patients (4%). According to
      Naranjo scale, in 6 patients (24%) the ADR were unlikely, 12 patients (48%) were
      given possible score, 3 patients (12%) were given probable score, and 4 patients
      (16%) were given definite scores. CONCLUSION: In the present study, the maximum
      patients were in the age group of 41-50 years. The most commonly prescribed drugs
      were timolol followed by dorzolamide, acetazolamide. Latanoprost was associated
      with maximum number of ADRs.

PMID- 24871931
TI  - HLA-B*1502 increases the risk of phenytoin or lamotrigine induced Stevens-Johnson
      Syndrome/toxic epidermal necrolysis: evidence from a meta-analysis of nine case
      control studies.
AB  - BACKGROUND AND STUDY AIMS: Stevens-Johnson syndrome (SJS) and toxic epidermal
      necrolysis (TEN) are fatal adverse cutaneous drug reactions which may be induced
      by phenytoin (PHT) or lamotrigine (LTG). The objective of this study was to
      analyze the association of human leukocyte antigen (HLA)-B*1502 and PHT or LTG
      induced SJS/TEN. PATIENTS AND METHODS: All the participants were epileptic
      patients and the SJS/TEN were induced by PHT or LTG. The presence or absence of
      the HLA-B*1502 allele of all the patients was determined. ISI Web of Knowledge,
      PubMed, ScienceDirect, EMBASE, and Cochrane Register of Controlled Trials
      (CENTRAL) data were searched for the literature published before April 2014. Meta
      analysis was performed using Review Manager 5.2 software. RESULTS: From 256
      citations, 6 English studies were included that involved 480 epilepsy patients.
      Meta-analysis showed that odd ratio (OR) of PHT and LTG were 5.65 [95% CI: 2.76
      11.57] and 4.51 [95% CI: 1.57-12.98], respectively. Funnel plot analysis showed
      symmetry, indicting less possible publication bias and the results were partly
      reliable. CONCLUSION: There is a significant association between HLA-B*1502 and
      PHT or LTG-induced SJS/TEN.

PMID- 24871933
TI  - Root canal treatment and special needs patients.
AB  - AIM: To identify current trends of root canal treatment for patients with special
      needs. METHODOLOGY: A postal questionnaire was sent to General Dentists in
      Victoria, Australia and Endodontists and Special Needs Dentists across Australia
      to determine the extent of root canal treatment performed on special needs
      patients. RESULTS: Over a four-month period, 1120 questionnaires were distributed
      with an overall response rate of 63.9% (n = 716). Response rates were 63.2% (n =
      655), 68.5% (n = 50) and 100.0% (n = 11) amongst General Dentists, Endodontists
      and Special Needs Dentists, respectively. Endodontists (95.7%) and Special Needs
      Dentists (100.0%) performed significantly more root canal treatment on adult
      patients with special needs compared with 51.2% of General Dentists, (P < 0.001
      and P = 0.001 respectively; Fisher's exact test). The most common reasons for not
      undertaking root canal treatment included limited cooperation, poor oral hygiene
      and uncontrolled movement. Amongst General Dentists, 75.7% opted for extraction
      in preference to root canal treatment. Significantly, more specialist
      practitioners performed root canal treatment utilizing conscious sedation (P <
      0.001) and general anaesthesia (P = 0.003). Most specialist practitioners (69.1%)
      had undertaken single-visit root canal treatment on special needs patients
      compared with only 29.7% of General Dentists (P < 0.001). CONCLUSIONS: Root canal
      treatment in special needs patients was more likely to be carried out by
      specialist dental practitioners who were more likely to utilize a pharmacological
      approach for behaviour guidance and to perform single-visit root canal treatment
      compared with General Dentists. A multidisciplinary approach for special needs
      patients who require root canal treatment provides an opportunity for these
      patients to retain their dentition.

PMID- 24871934
TI  - Up-cycling waste glass to minimal water adsorption/absorption lightweight
      aggregate by rapid low temperature sintering: optimization by dual process
      mixture response surface methodology.
AB  - Mixed color waste glass extracted from municipal solid waste is either not
      recycled, in which case it is an environmental and financial liability, or it is
      used in relatively low value applications such as normal weight aggregate. Here,
      we report on converting it into a novel glass-ceramic lightweight aggregate
      (LWA), potentially suitable for high added value applications in structural
      concrete (upcycling). The artificial LWA particles were formed by rapidly
      sintering (<10 min) waste glass powder with clay mixes using sodium silicate as
      binder and borate salt as flux. Composition and processing were optimized using
      response surface methodology (RSM) modeling, and specifically (i) a combined
      process-mixture dual RSM, and (ii) multiobjective optimization functions. The
      optimization considered raw materials and energy costs. Mineralogical and
      physical transformations occur during sintering and a cellular vesicular glass
      ceramic composite microstructure is formed, with strong correlations existing
      between bloating/shrinkage during sintering, density and water
      adsorption/absorption. The diametrical expansion could be effectively modeled via
      the RSM and controlled to meet a wide range of specifications; here we optimized
      for LWA structural concrete. The optimally designed LWA is sintered in
      comparatively low temperatures (825-835  degrees C), thus potentially saving
      costs and lowering emissions; it had exceptionally low water
      adsorption/absorption (6.1-7.2% w/wd; optimization target: 1.5-7.5% w/wd); while
      remaining substantially lightweight (density: 1.24-1.28 g.cm(-3); target: 0.9-1.3
      g.cm(-3)). This is a considerable advancement for designing effective
      environmentally friendly lightweight concrete constructions, and boosting
      resource efficiency of waste glass flows. 

PMID- 24871932
TI  - Osteoporosis and multiple sclerosis: risk factors, pathophysiology, and
      therapeutic interventions.
AB  - Multiple sclerosis (MS) is a chronic inflammatory-demyelinating disease of the
      nervous system. There has been mounting evidence showing that MS is associated
      with increased risk of osteoporosis and fractures. The development of
      osteoporosis in MS patients can be related to the cumulative effects of various
      factors. This review summarizes the common risk factors and physiologic pathways
      that play a role in development of osteoporosis in MS patients. Physical
      inactivity and reduced mechanical load on the bones (offsetting gravity) is
      likely the major contributing factor for osteoporosis in MS. Additional possible
      factors leading to reduced bone mass are low vitamin D levels, and use of
      medications such as glucocorticoids and anticonvulsants. The role of the
      inflammatory processes related to the underlying disease is considered in the
      context of the complex bone metabolism. The known effect of different MS disease
      modifying therapies on bone health is limited. An algorithm for diagnosis and
      management of osteoporosis in MS is proposed. 

PMID- 24871935
TI  - Tracheal rupture related to endotracheal intubation after thyroid surgery: a case
      report and systematic review.
AB  - Tracheobronchial rupture is an uncommon but potentially serious complication of
      endotracheal intubation. The most likely cause of tracheal injury is massive
      overinflation of the endotracheal tube cuff and pre-existing tracheal wall
      weakness. We review the relevant literature and predisposing factors contributing
      to this complication. Only articles that reported at least the demographic data
      (age and sex), the treatment performed and the outcome were included. Papers that
      did not detail these variables were excluded. We also focus on a case of tracheal
      laceration after tracheal intubation in a patient with severe thyroid carcinoma.
      This patient received surgical repair and recovered uneventfully. Two hundred and
      eight studies that reported cases or case series were selected for analysis. Most
      of the reported cases (57.2%) showed an uneventful recovery after surgical
      therapy. The overall mortality was 19.2% (40 patients). Our patient too recovered
      without any serious complication. Careful prevention, early detection and proper
      treatment of the problem are necessary when tracheal rupture occurs. The
      morbidity and mortality associated with tracheal injury mandate a high level of
      suspicion and expedient management. 

PMID- 24871936
TI  - Multimeric disintegrin protein polymer fusions that target tumor vasculature.
AB  - Recombinant protein therapeutics have increased in number and frequency since the
      introduction of human insulin, 25 years ago. Presently, proteins and peptides are
      commonly used in the clinic. However, the incorporation of peptides into
      clinically approved nanomedicines has been limited. Reasons for this include the
      challenges of decorating pharmaceutical-grade nanoparticles with proteins by a
      process that is robust, scalable, and cost-effective. As an alternative to
      covalent bioconjugation between a protein and nanoparticle, we report that
      biologically active proteins may themselves mediate the formation of small
      multimers through steric stabilization by large protein polymers. Unlike
      multistep purification and bioconjugation, this approach is completed during
      biosynthesis. As proof-of-principle, the disintegrin protein called vicrostatin
      (VCN) was fused to an elastin-like polypeptide (A192). A significant fraction of
      fusion proteins self-assembled into multimers with a hydrodynamic radius of 15.9
      nm. The A192-VCN fusion proteins compete specifically for cell-surface integrins
      on human umbilical vein endothelial cells (HUVECs) and two breast cancer cell
      lines, MDA-MB-231 and MDA-MB-435. Confocal microscopy revealed that, unlike
      linear RGD-containing protein polymers, the disintegrin fusion protein undergoes
      rapid cellular internalization. To explore their potential clinical applications,
      fusion proteins were characterized using small animal positron emission
      tomography (microPET). Passive tumor accumulation was observed for control
      protein polymers; however, the tumor accumulation of A192-VCN was saturable,
      which is consistent with integrin-mediated binding. The fusion of a protein
      polymer and disintegrin results in a higher intratumoral contrast compared to
      free VCN or A192 alone. Given the diversity of disintegrin proteins with
      specificity for various cell-surface integrins, disintegrin fusions are a new
      source of biomaterials with potential diagnostic and therapeutic applications. 

PMID- 24871942
TI  - Association football and the representation of homosexuality by the print media:
      a case study of Anton Hysen.
AB  - In March 2011, Anton Hysen (a semiprofessional footballer currently playing in
      the Swedish fourth division) became only the second association football (soccer)
      player of any professional disposition to publicly declare his homosexuality
      while still playing the game. This article provides a textual analysis of the
      print media's reaction to Hysen coming out and examines whether, in 2011, they
      portray more inclusive notions toward homosexuality than they did in 1990 when
      British footballer Justin Fashanu came out. The results advance inclusive
      masculinity theory as a number of print media sources (mostly British) interview
      Hysen in the weeks immediately after he came out and publish articles that
      challenge homophobia. Highlighting a change since 1990, a significant number of
      articles stress the need for the key stakeholders in football (players, fans,
      clubs, agents, the authorities, and the media) to accept gay players. 

PMID- 24871941
TI  - Association between race and age in survival after trauma.
AB  - IMPORTANCE: Racial disparities in survival after trauma are well described for
      patients younger than 65 years. Similar information among older patients is
      lacking because existing trauma databases do not include important patient
      comorbidity information. OBJECTIVE: To determine whether racial disparities in
      trauma survival persist in patients 65 years or older. DESIGN, SETTING, AND
      PARTICIPANTS: Trauma patients were identified from the Nationwide Inpatient
      Sample (January 1, 2003, through December 30, 2010) using International
      Classification of Diseases, Ninth Revision, Clinical Modification diagnosis
      codes. Injury severity was ascertained by applying the Trauma Mortality
      Prediction Model, and patient comorbidities were quantified using the Charlson
      Comorbidity Index. MAIN OUTCOMES AND MEASURES: In-hospital mortality after trauma
      for blacks vs whites for younger (16-64 years of age) and older (>=65 years of
      age) patients was compared using 3 different statistical methods: univariable
      logistic regression, multivariable logistic regression with and without
      clustering for hospital effects, and coarsened exact matching. Model covariates
      included age, sex, insurance status, type and intent of injury, injury severity,
      head injury severity, and Charlson Comorbidity Index. RESULTS: A total of
      1,073,195 patients were included (502,167 patients 16-64 years of age and 571,028
      patients >=65 years of age). Most older patients were white (547,325 [95.8%]),
      female (406 158 [71.1%]), and insured (567,361 [99.4%]) and had Charlson
      Comorbidity Index scores of 1 or higher (323,741 [56.7%]). The unadjusted odds
      ratios (ORs) for death in blacks vs whites were 1.35 (95% CI, 1.28-1.42) for
      patients 16 to 64 years of age and 1.00 (95% CI, 0.93-1.08) for patients 65 years
      or older. After risk adjustment, racial disparities in survival persisted in the
      younger black group (OR, 1.21; 95% CI, 1.13-1.30) but were reversed in the older
      group (OR, 0.83; 95% CI, 0.76-0.90). This finding was consistent across all 3
      statistical methods. CONCLUSIONS AND RELEVANCE: Different racial disparities in
      survival after trauma exist between white and black patients depending on their
      age group. Although younger white patients have better outcomes after trauma than
      younger black patients, older black patients have better outcomes than older
      white patients. Exploration of this paradoxical finding may lead to a better
      understanding of the mechanisms that cause disparities in trauma outcomes.

PMID- 24871937
TI  - Developmental toxicity assay using high content screening of zebrafish embryos.
AB  - Typically, time-consuming standard toxicological assays using the zebrafish
      (Danio rerio) embryo model evaluate mortality and teratogenicity after exposure
      during the first 2 days post-fertilization. Here we describe an automated image
      based high content screening (HCS) assay to identify the teratogenic/embryotoxic
      potential of compounds in zebrafish embryos in vivo. Automated image acquisition
      was performed using a high content microscope system. Further automated analysis
      of embryo length, as a statistically quantifiable endpoint of toxicity, was
      performed on images post-acquisition. The biological effects of ethanol,
      nicotine, ketamine, caffeine, dimethyl sulfoxide and temperature on zebrafish
      embryos were assessed. This automated developmental toxicity assay, based on a
      growth-retardation endpoint should be suitable for evaluating the effects of
      potential teratogens and developmental toxicants in a high throughput manner.
      This approach can significantly expedite the screening of potential teratogens
      and developmental toxicants, thereby improving the current risk assessment
      process by decreasing analysis time and required resources.

PMID- 24871943
TI  - Redox or death: checking on fetal myogenesis.
AB  - Reporting in this issue of Developmental Cell, L'honore et al. (2014) show that a
      network composed of Pitx2/Pitx3 and downstream antioxidant enzymes protects
      differentiating skeletal muscle from excessive reactive oxygen species production
      during fetal myogenesis. Genetic deficiency of Pitx2/Pitx3 results in
      irreversible oxidative DNA damage and apoptosis, impairing skeletal muscle
      development.

PMID- 24871939
TI  - Function and regulation of dynein in mitotic chromosome segregation.
AB  - Cytoplasmic dynein is a large minus-end-directed microtubule motor complex,
      involved in many different cellular processes including intracellular
      trafficking, organelle positioning, and microtubule organization. Furthermore,
      dynein plays essential roles during cell division where it is implicated in
      multiple processes including centrosome separation, chromosome movements, spindle
      organization, spindle positioning, and mitotic checkpoint silencing. How is a
      single motor able to fulfill this large array of functions and how are these
      activities temporally and spatially regulated? The answer lies in the unique
      composition of the dynein motor and in the interactions it makes with multiple
      regulatory proteins that define the time and place where dynein becomes active.
      Here, we will focus on the different mitotic processes that dynein is involved
      in, and how its regulatory proteins act to support dynein. Although dynein is
      highly conserved amongst eukaryotes (with the exception of plants), there is
      significant variability in the cellular processes that depend on dynein in
      different species. In this review, we concentrate on the functions of cytoplasmic
      dynein in mammals but will also refer to data obtained in other model organisms
      that have contributed to our understanding of dynein function in higher
      eukaryotes. 

PMID- 24871944
TI  - Genome stress response in early development.
AB  - Cells with irreparable genomic damage pose a problem for development and must be
      eliminated to prevent disease. Reporting in this issue of Developmental Cell,
      Iampietro et al. (2014) describe a mechanism in Drosophila that removes damaged
      nuclei from syncytial blastoderm embryos via DNA damage checkpoint kinase
      mediated retention of specific mRNAs within the nucleus.

PMID- 24871946
TI  - Redox regulation by Pitx2 and Pitx3 is critical for fetal myogenesis.
AB  - During development, major metabolic changes occur as cells become more
      specialized within a lineage. In the case of skeletal muscle, differentiation is
      accompanied by a switch from a glycolytic proliferative progenitor state to an
      oxidative postmitotic differentiated state. Such changes require extensive
      mitochondrial biogenesis leading to increased reactive oxygen species (ROS)
      production that needs to be balanced by an antioxidant system. Our analysis of
      double conditional Pitx2/3 mouse mutants, both in vivo during fetal myogenesis
      and ex vivo in primary muscle cell cultures, reveals excessive upregulation of
      ROS levels leading to DNA damage and apoptosis of differentiating cells. This is
      a consequence of downregulation of Nrf1 and genes for antioxidant enzymes, direct
      targets of Pitx2/3, leading to decreased expression of antioxidant enzymes, as
      well as impairment of mitochondrial function. Our analysis identifies Pitx2 and
      Pitx3 as key regulators of the intracellular redox state preventing DNA damage as
      cells undergo differentiation.

PMID- 24871945
TI  - APC(Cdc20) suppresses apoptosis through targeting Bim for ubiquitination and
      destruction.
AB  - Anaphase-promoting complex Cdc20 (APC(Cdc20)) plays pivotal roles in governing
      mitotic progression. By suppressing APC(Cdc20), antimitotic agents activate the
      spindle-assembly checkpoint and induce apoptosis after prolonged treatment,
      whereas depleting endogenous Cdc20 suppresses tumorigenesis in part by triggering
      mitotic arrest and subsequent apoptosis. However, the molecular mechanism(s)
      underlying apoptosis induced by Cdc20 abrogation remains poorly understood. Here,
      we report the BH3-only proapoptotic protein Bim as an APC(Cdc20) target, such
      that depletion of Cdc20 sensitizes cells to apoptotic stimuli. Strikingly, Cdc20
      and multiple APC-core components were identified in a small interfering RNA
      screen that, upon knockdown, sensitizes otherwise resistant cancer cells to
      chemoradiation in a Bim-dependent manner. Consistently, human adult T cell
      leukemia cells that acquire elevated APC(Cdc20) activity via expressing the Tax
      viral oncoprotein exhibit reduced Bim levels and resistance to anticancer agents.
      These results reveal an important role for APC(Cdc20) in governing apoptosis,
      strengthening the rationale for developing specific Cdc20 inhibitors as effective
      anticancer agents.

PMID- 24871947
TI  - Membrane-bound methyltransferase complex VapA-VipC-VapB guides epigenetic control
      of fungal development.
AB  - Epigenetic and transcriptional control of gene expression must be coordinated in
      response to external signals to promote alternative multicellular developmental
      programs. The membrane-associated trimeric complex VapA-VipC-VapB controls a
      signal transduction pathway for fungal differentiation. The VipC-VapB
      methyltransferases are tethered to the membrane by the FYVE-like zinc finger
      protein VapA, allowing the nuclear VelB-VeA-LaeA complex to activate
      transcription for sexual development. Once the release from VapA is triggered,
      VipC-VapB is transported into the nucleus. VipC-VapB physically interacts with
      VeA and reduces its nuclear import and protein stability, thereby reducing the
      nuclear VelB-VeA-LaeA complex. Nuclear VapB methyltransferase diminishes the
      establishment of facultative heterochromatin by decreasing histone 3 lysine 9
      trimethylation (H3K9me3). This favors activation of the regulatory genes brlA and
      abaA, which promote the asexual program. The VapA-VipC-VapB methyltransferase
      pathway combines control of nuclear import and stability of transcription factors
      with histone modification to foster appropriate differentiation responses.

PMID- 24871950
TI  - A taxonomic revision of the Kermesidae (Hemiptera: Coccoidea) in Israel, with a
      description of a new species.
AB  - A taxonomic revision is presented of the six Kermesidae species from Israel,
      namely, Kermes echinatus Balachowsky, K. greeni Bodenheimer, K. nahalali
      Bodenheimer, K. spatulatus Balachowsky, Nidularia balachowskii Bodenheimer, and
      K. hermonensis Spodek & Ben-Dov sp. n. Kermes bytinskii Sternlicht, syn. n. is
      established as a junior synonym of K. nahalali Bodenheimer and a lectotype for K.
      nahalali is designated. This study includes descriptions, redescriptions and
      illustrations of the adult female, adult male and all developmental stages for
      these six species. Keys are provided to distinguish between instars, adult
      females, adult males and immature stages for all species.

PMID- 24871951
TI  - Biogeographical regionalisation of the Neotropical region.
AB  - A biogeographic regionalisation of the Neotropical region is proposed as a
      hierarchical classification of sub-regions, dominions, provinces and districts.
      This regionalisation is based on biogeographic analyses of terrestrial plant and
      animal taxa, and seeks to provide universality, objectivity and stability, such
      that it can be applied when describing distributional areas of particular taxa or
      comparing different biogeographic analyses. The Neotropical region is currently
      comprised of three sub-regions (Antillean, Brazilian and Chacoan), two transition
      zones (Mexican and South American), seven dominions (Mesoamerican, Pacific,
      Boreal Brazilian, Southwestern Amazonian, Southeastern Amazonian, Chacoan and
      Parana) and 53 provinces. For some of the latter, sub-provinces and districts are
      recognized. Complete synonymies and brief descriptions of the areas are provided,
      as well as the endemic taxa that diagnose the different provinces. 

PMID- 24871949
TI  - Membrane-localized estrogen receptor alpha is required for normal organ
      development and function.
AB  - Steroid receptors are found in discrete cellular locations, but it is unknown
      whether extranuclear pools are necessary for normal organ development. To assess
      this, we developed a point mutant estrogen receptor alpha (ERalpha) knockin mouse
      (C451A) that precludes palmitoylation and membrane trafficking of the steroid
      receptor in all organs. Homozygous knockin female mice (nuclear-only ERalpha
      [NOER]) show loss of rapid signaling that occurs from membrane ERalpha in wild
      type mice. Multiple developmental abnormalities were found, including
      infertility, relatively hypoplastic uteri, abnormal ovaries, stunted mammary
      gland ductal development, and abnormal pituitary hormone regulation in NOER mice.
      These abnormalities were rescued in heterozygous NOER mice that were comparable
      to wild-type mice. mRNAs implicated in organ development were often poorly
      stimulated by estrogen only in homozygous NOER mice. We conclude that many organs
      require membrane ERalpha and resulting signal transduction to collaborate with
      nuclear ERalpha for normal development and function.

PMID- 24871952
TI  - New insights into polyphyly of the harpacticoid genus Delavalia (Crustacea,
      Copepoda) through morphological and molecular study of an unprecedented diversity
      of sympatric species in a small South Korean bay.
AB  - Polyphyly of the genus Delavalia Brady, 1869 has been postulated previously based
      on intuitive methods, but no phylogenetic study was ever conducted. A chance
      discovery of seven sympatric species of this genus in the highly industrialized
      Gwangyang Bay in South Korea, in addition to one species each from the closely
      related genera Stenhelia Boeck, 1865 and Onychostenhelia Ito, 1979, prompted a
      renewed interest in the phylogenetic relationships within the subfamily
      Stenheliinae Brady, 1880. Additional surveys along the Korean coast failed to
      produce Delavalia species, but comparative material was sourced from Posyet Bay
      in the Russian Far East. Aims of this study were to reconstruct phylogenetic
      relationships of the newly collected stenheliins using molecular methods, test
      the hypothesized polyphyly of Delavalia, formally describe any resulting
      monophyletic units, perform a comparative study of traditional morphological and
      novel micro-morphological characters, and describe all new Delavalia species. A
      fragment of the mtCOI gene was successfully PCR-amplified from 23 stenheliin
      specimens and an additional 300 specimens were studied for morphological
      characters. All phylogenetic analyses supported the presence of at least eight
      genetically divergent lineages, most with very high bootstrap values, and the
      polyphyletic nature of Delavalia is demonstrated. Three new genera, each
      supported by molecular data and a number of morphological synapomorphies, were
      erected to accommodate the newly discovered species and some previously described
      members of Delavalia: Wellstenhelia gen. nov., Itostenhelia gen. nov., and
      Willenstenhelia gen. nov. The Chinese Wellstenhelia qingdaoensis (Ma & Li, 2011)
      comb. nov. is recorded for the first time in Korea, and six new species are
      described from Gwangyang Bay: Wellstenhelia calliope sp. nov., Wellstenhelia clio
      sp. nov., Wellstenhelia erato sp. nov., Wellstenhelia euterpe sp. nov.,
      Itostenhelia polyhymnia sp. nov., and Willenstenhelia thalia sp. nov.
      Additonally, Itostenhelia golikovi (Chisleno, 1978) comb. nov. is redescribed
      from newly collected material from the type locality in Russia and its male
      described for the first time, while Wellstenhelia melpomene sp. nov.,
      Willenstenhelia urania sp. nov., and Willenstenhelia terpsichore sp. nov. are
      established as new names for previously reported populations of two presumably
      widely distributed Delavalia species. 

PMID- 24871948
TI  - Estrogen defines the dorsal-ventral limit of VEGF regulation to specify the
      location of the hemogenic endothelial niche.
AB  - Genetic control of hematopoietic stem and progenitor cell (HSPC) function is
      increasingly understood; however, less is known about the interactions specifying
      the embryonic hematopoietic niche. Here, we report that 17beta-estradiol (E2)
      influences production of runx1+ HSPCs in the AGM region by antagonizing VEGF
      signaling and subsequent assignment of hemogenic endothelial (HE) identity.
      Exposure to exogenous E2 during vascular niche development significantly
      disrupted flk1+ vessel maturation, ephrinB2+ arterial identity, and specification
      of scl+ HE by decreasing expression of VEGFAa and downstream arterial Notch
      pathway components; heat shock induction of VEGFAa/Notch rescued E2-mediated
      hematovascular defects. Conversely, repression of endogenous E2 activity
      increased somitic VEGF expression and vascular target regulation, shifting
      assignment of arterial/venous fate and HE localization; blocking E2 signaling
      allowed venous production of scl+/runx1+ cells, independent of arterial identity
      acquisition. Together, these data suggest that yolk-derived E2 sets the ventral
      boundary of hemogenic vascular niche specification by antagonizing the dorsal
      ventral regulatory limits of VEGF.

PMID- 24871953
TI  - Patient-prosthesis mismatch increases the mean platelet volume in patients with
      aortic valve replacement.
AB  - PURPOSE: Patient-prosthesis mismatch (PPM) is defined when the ratio of the
      effective orifice area of the normally functioning prosthetic valve to the body
      surface area of the patient is <0.85 cm(2)/m(2). The aim of this study was to
      assess the measurements of the mean platelet volume (MPV) as an indicator of
      platelet activation in patients with PPM. METHODS: A total of 109 patients with
      isolated aortic valve replacement (AVR) procedures with a mechanical prosthesis
      and a control group from a normal population of 102 people compatible in terms of
      age and sex were chosen for the study. The AVR group was subdivided into a PPM
      group (n = 41) and non-PPM group (n = 68). All patients and control participants
      underwent echocardiographic examinations, with simultaneous measurements of the
      serum MPV values. RESULTS: The MPV measurements were significantly higher in the
      patients with AVR compared to the control group (8.97 +/- 0.93 vs. 8.26 +/- 0.14,
      p < 0.001). Higher results were also obtained in the patients with PPM compared
      to the non-PPM group (9.36 +/- 0.61 vs. 8.73 +/- 1.01, p < 0.001). The platelet
      counts were found to be similar in both groups (p > 0.05). CONCLUSIONS: We have
      herein shown that the PPM patients had a significantly higher MPV compared to the
      patients with AVR without PPM and healthy subjects.

PMID- 24871956
TI  - Rhodium(III)-catalyzed intramolecular amidoarylation and hydroarylation of alkyne
      via C-H activation: switchable synthesis of 3,4-fused tricyclic indoles and
      chromans.
AB  - The controllable intramolecular amidoarylation and hydroarylation of alkynes has
      been achieved via rhodium(III)-catalyzed C-H activation. The merger of two
      distinct reaction pathways allows for the development of atom- and step-economic
      protocols for the switchable synthesis of 3,4-fused indoles and chromans,
      respectively.

PMID- 24871954
TI  - Differences in microorganism growth on various dressings used to cover injection
      sites: inspection of the risk of catheter-related bloodstream infections caused
      by Gram-negative bacilli.
AB  - PURPOSES: Sepsis caused by Gram-negative bacilli (GNB) is the most serious
      catheter-related bloodstream infection. However, the cause(s) of GNB propagation
      on the skin around needle or catheter insertion sites remain unclear. This
      observational study aimed to assess the differences in the microbial growth among
      various types of dressings used to cover injection sites, with a particular focus
      on GNB. METHODS: We analyzed the bacterial populations on three types of surgical
      dressings; Tegaderm I.V. (semi-permeable, 27 sheets), IV3000 (highly permeable,
      34 sheets) and Tegaderm CHG (chlorhexidine-impregnated, 26 sheets). The
      peripheral catheter site dressing was replaced every 3 days or when there was
      leakage or pain at the catheter site. RESULTS: Bacterial growth was observed in
      all Tegaderm I.V. and IV3000 sheets and in only one (3.8%) Tegaderm CHG sheet.
      The GNB detection rate was significantly lower in the IV3000 group (2.9%) than in
      the Tegaderm I.V. group (63.0%). No GNB growth was identified in the Tegaderm CHG
      group. CONCLUSIONS: Semi-permeable dressings were insufficient to prevent GNB
      infections, whereas highly permeable or chlorhexidine-impregnated dressings could
      prevent GNB infections. Chlorhexidine-impregnated dressings can control almost
      all bacterial growth.

PMID- 24871957
TI  - High-performance liquid chromatography analysis of phenolic acid, flavonoid, and
      phenol contents in various natural Yemeni honeys using multi-walled carbon
      nanotubes as a solid-phase extraction adsorbent.
AB  - A simple method has been described for simultaneous determination of phenolic
      acid, flavonoid, and other phenol contents in various natural honey samples
      collected from various regions of Yemen. Multi-walled carbon nanotubes were used
      as a solid-phase adsorbent for extraction of the polyphenols from honey samples.
      The total contents of phenolic acids, flavonoids, and phenolic components of the
      12 different samples were found in the range of 363-2658, 261-1646, and 224-1355
      MUg/100 g of honey samples, respectively. The major phenolic acid, flavonoid, and
      phenolic compound in these samples were found to be 4-hydroxybenzoic acid (1410
      MUg/100 g), chrysin (850 MUg/100 g), and cinnamic acid (1336 MUg/100 g),
      respectively. A total of 25 compounds (10 phenolic acids, 9 flavonoids, and 6
      phenols) were analyzed, and a total of 24 were detected, while only 23 compounds
      were determined quantitatively in the honey samples. The developed method showed
      potential usefulness for the analysis of honey and was used for the determination
      of polyphenols in honey extracts. 

PMID- 24871958
TI  - Investigating the long-term consequences of adverse medical events among older
      adults.
AB  - OBJECTIVE: To investigate the long-term effect of medically serious adverse
      medical events (AMEs) among older adults. METHODS: We linked nationally
      representative survey and claims data from the Medicare Current Beneficiary
      Survey (1998-2004) with non-response files (1999-2005) and the Area Resource
      File, providing 12,541 beneficiaries with 428,373 person-months for analysis.
      Latent class analysis was used to assign severity status to episodes. Multinomial
      logistic regression was used to identify AME risk factors. The long-term
      consequences of AMEs on Medicare expenditures were examined by population average
      models. Survival analyses examined the long-term risk of death. RESULTS: Nearly
      19% of participants experienced at least one AME, with 62% from outpatient
      claims. The risk of AMEs is greater among participants in poorer health, and
      increases with comorbidity and with impairment in performing activities of daily
      living or instrumental activities of daily living. Medicare expenditures during
      an AME episode increased sharply and remained higher than what would have
      otherwise been expected in quarters following an AME episode, and failed to
      return to pre-AME expenditure levels. Differences in survival rates were
      observable long after the AME episode concluded, with only 55% of the patients
      sustaining an AME surviving to the end of the study. In contrast, nearly 80% of
      those without an AME were estimated to have survived. CONCLUSIONS: The impacts of
      AMEs are observable over extended periods of time and are associated with
      considerable excess mortality and costs. Efforts to monitor and prevent AMEs in
      both acute care and outpatient settings are warranted.

PMID- 24871959
TI  - Inequalities in unintentional injuries between indigenous and non-indigenous
      children: a systematic review.
AB  - BACKGROUND: Indigenous children suffer a disproportionally high burden of
      unintentional injuries. A more detailed understanding of the underlying causes,
      risk factors and gaps in research is required to inform prevention efforts and
      direct future research. The aim of this review was to systematically assess the
      evidence regarding differences in rates of unintentional injuries between
      indigenous and non-indigenous children and to identify leading causes and
      underlying risk factors contributing to these differences. METHOD: We
      systematically searched the literature including 10 electronic databases,
      institutional websites and reference lists of relevant studies. Due to the
      substantial heterogeneity between studies, results were summarised in a narrative
      synthesis and no meta-analysis was carried out. RESULTS: A total of 39 studies
      were included in this review. Most studies were descriptive and only five
      adjusted for potential confounding in the analysis. Indigenous to non-indigenous
      rate ratios for morbidity and mortality for unintentional injury ranged from 1.2
      to 2.3 and 1.8 to 8.2, respectively. The difference varied greatly by cause of
      injury and between studies, ranging from a reduced risk of hospitalisation due to
      fall injuries to a 17-fold increased risk of mortality due to pedestrian
      injuries. Burns, poisoning and transport injuries were the major contributors to
      the increased injury burden in indigenous children. The studies offered only
      limited insight into the underlying causes of these differences, but
      socioeconomic status and parents' educational attainment were contributing
      factors. CONCLUSIONS: Indigenous children experience a significantly higher
      burden of morbidity and mortality from unintentional injuries across different
      indigenous communities worldwide. Most of these injuries are highly preventable,
      presenting substantial potential to improve indigenous child health. However,
      there is limited evidence to illuminate the underlying risk factors for
      unintentional injuries in indigenous children, and this is a priority for further
      research.

PMID- 24871961
TI  - Mouse studies on inhibitors of Plasmodium falciparum Hsp90: progress and
      challenges.
AB  - This review highlights studies conducted in murine models to evaluate the
      efficacy of compounds targeting Heat shock protein (Hsp) 90 of malaria. Both
      advances achieved and limitations that exist are highlighted.

PMID- 24871960
TI  - Evaluating a website to teach children safety with dogs.
AB  - BACKGROUND: Paediatric dog bites are a significant public health problem
      worldwide. Existing prevention programmes focused on altering children's risky
      behaviour with pet dogs tend to be atheoretical and only moderately effective.
      OBJECTIVE: Test efficacy of a website to train young children in relevant
      cognitive skills to be safe with pet dogs in their home. SETTING: Birmingham,
      Alabama, USA. METHODS: A randomised trial will be conducted with an expected
      sample of two groups of 34 children (total N=68) ages 4-6 years. One group will
      engage in the newly designed website at home for 2 weeks and the other group will
      engage in a control website on transportation safety for an equivalent amount of
      time. All participants will complete a battery of laboratory-based tests to
      assess safety with dogs and cognitive functioning at baseline and
      postintervention. OUTCOME MEASURES: Primary analyses will be conducted through
      linear mixed models testing change over time. Children's cognitive functioning,
      knowledge about safety with dogs, and behaviour with dogs in simulation and in
      vivo will serve as the primary outcomes. CLINICAL TRIAL REGISTRATION: This study
      is exempt from registry at the US government website,
      http://www.clinicaltrials.gov, based on being a behavioural trial in the early
      phases of testing.

PMID- 24871963
TI  - Estimation of the disposition index based on components of metabolic syndrome.
AB  - Decreased insulin sensitivity (IS) and impaired insulin secretion are major
      pathological features of type 2 diabetes (T2DM). The product of these factors is
      the disposition index (DI). We aimed to develop an equation for predicting DI. We
      enrolled 167 participants in our study. We randomly assigned 126 (75%) of the
      participants to the study group, whose data would be used to build the equation
      for estimating the DI. The remaining 41 participants comprised the external
      validation group. A frequently sampled intravenous glucose-tolerance test was
      performed for all participants, and the IS, the glucose sensitivity, the acute
      insulin response to the glucose load, and the DI were determined. Three factors
      were selected from multiple linear regression analysis, and we constructed the
      equation log (DI) = 2.449 - 0.113 * fasting plasma glucose + 0.046 * body mass
      index - 0.612 * high-density lipoprotein cholesterol. Using this equation, the
      calculated log (DI) significantly correlated with the measured log (DI) in the
      external validation group (r = 0.428, p = 0.007). By using the equation based on
      the demographic data and measurements of metabolic syndrome components, the DI
      could be predicted with acceptable accuracy (r = 0.428). Because of the
      relationships between the MetS and demographic parameters, this method of
      predicting DI may help further clinicians' understanding of the underlying
      pathological mechanisms in T2DM. 

PMID- 24871964
TI  - Plasma free metanephrines in the diagnosis of pheochromocytoma: diagnostic
      accuracy and strategies for Japanese patients.
AB  - Measuring the levels of the plasma free metanephrines (PFMs) represents a
      recently developed and promising test for the diagnosis of pheochromocytoma in
      the United States and Europe. As this test has not yet been evaluated in Japan,
      it is necessary to evaluate the diagnostic efficacy of measuring the levels of
      PFMs compared with the standard measurement of the urinary excretion of
      metanephrines (uMNs) whose reliability is well established to detect of
      pheochromocytoma. A total of 101 Japanese subjects clinically suspected of having
      pheochromocytoma in were included in this study. Subsequently, we prospectively
      measured the PFMs levels in all patients, compared with those of biochemical
      markers of the catecholamine secretion and metabolisms in the plasma and urine.
      All subjects with adrenal tumors underwent tumor excision. Data were available
      for 84 of the 101 patients, 47 of whom had histopathologically proven
      pheochromocytoma and 37 were finally diagnosed with non-pheochromocytoma. The
      results of comparisons in the accuracy of measurement for diagnosis of
      pheochromocytoma between PFMs and the urinary excretion of metanephrines (uMNs)
      were 0.980 VS 0.951 for AUC of receiver operatorating characteristic (ROC) curve,
      0.957 VS 0.894 for sensitivity, and 0.973 VS 0.946 for specificity, respectively.
      Although the differences were small, the results of our study definitely
      demonstrated that measurement of PFMs was not inferior to standard urinary
      metanephrines (uMNs) measurement, which is established to be the most reliable
      biochemical method to detect pheochromocytoma. This study clearly shows measuring
      the PFMs levels to be a reliable and efficient method for diagnosing
      pheochromocytoma in Japanese patients, as demonstrated in previous reports. 

PMID- 24871967
TI  - Cold-activated brown adipose tissue in human adults: methodological issues.
AB  - The relevance of functional brown adipose tissue (BAT) depots in human adults was
      undisputedly proven approximately seven years ago. Here we give an overview of
      all dedicated studies that were published on cold-induced BAT activity in adult
      humans that appeared since then. Different cooling protocols and imaging
      techniques to determine BAT activity are reviewed. BAT activation can be achieved
      by means of air- or water-cooling protocols. The most promising approach is
      individualized cooling, during which subjects are studied at the lowest
      temperature for nonshivering condition, probably revealing maximal nonshivering
      thermogenesis. The highest BAT prevalence (i.e., close to 100%) is observed using
      the individualized cooling protocol. Currently, the most widely used technique to
      study the metabolic activity of BAT is deoxy-2-[18F]fluoro-d-glucose ([18F]FDG)
      positron emission tomography/computed tomography (PET/CT) imaging. Dynamic
      imaging provides quantitative information about glucose uptake rates, whereas
      static imaging reflects overall BAT glucose uptake, localization, and
      distribution. In general, standardized uptake values (SUV) are used to quantify
      BAT activity. An accurate determination of total BAT volume is hampered by the
      limited spatial resolution of the PET image, leading to spillover. Different
      research groups use different SUV threshold values, which make it difficult to
      directly compare BAT activity levels between studies. Another issue is the
      comparison of [18F]FDG uptake in BAT with respect to other tissues or upon with
      baseline values. This comparison can be performed by using the "fixed volume"
      methodology. Finally, the potential use of other relatively noninvasive methods
      to quantify BAT, like magnetic resonance imaging or thermography, is discussed.

PMID- 24871968
TI  - Gold(I)-promoted heterocyclization of internal alkynes: a comparative study of
      direct metallate 5-endo-dig cyclization versus a stepwise cyclization.
AB  - With cationic gold catalysts, internal alkynes bearing both propargylic acyloxy
      groups and tosylamide pronucleophiles were found to cyclize to give either five-
      or six-membered ring nitrogen heterocycles. A wide variety of gold catalysts,
      counterions, and solvents were examined to elucidate their effect on product
      distribution. In most cases, the direct 5-endo-dig cyclization was found to be
      the major pathway leading to good yields of dehydropyrrolidine products. Alkyne
      substrates bearing additional normal alkyl substituents at the propargylic
      position gave dehydropiperidines as the major product. This pathway is thought to
      proceed by way of a 1,2- Rautenstrauch rearrangement to produce a vinyl gold(I)
      carbene, which undergoes conjugate addition by the nitrogen pronucleophile.
      Structural and electronic factors were studied in the nitrogen pronucleophile and
      in the migrating acyloxy group. Each was found to have a minor effect on the
      product ratio. 

PMID- 24871965
TI  - Neurology of rheumatologic disorders.
AB  - Rheumatologic diseases encompass autoimmune and inflammatory disorders of the
      joints and soft tissues that often involve multiple organ systems, including the
      central and peripheral nervous systems. Common features include constitutional
      symptoms, arthralgia and arthritis, myalgia, and sicca symptoms. Neurological
      manifestations may present in patients with preexisting rheumatologic diagnoses,
      occur concurrently with systemic signs and symptoms, or precede systemic
      manifestations by months to years. Rheumatic disorders presenting as neurological
      syndromes may pose diagnostic challenges. Advances in immunosuppressive treatment
      of rheumatologic disease have expanded the treatment armamentarium. However,
      serious neurotoxic effects have been reported with both old and newer agents.
      Familiarity with neurological manifestations of rheumatologic diseases,
      diagnosis, and potential nervous system consequences of treatment is important
      for rapid diagnosis and appropriate intervention. This article briefly reviews
      the diverse neurological manifestations and key clinical features of rheumatic
      disorders and the potential neurological complications of agents commonly used
      for treatment. 

PMID- 24871969
TI  - Self-inflicted burn injuries in the Australian context.
AB  - OBJECTIVE: The primary objective was to calculate the number of self-inflicted
      burn injuries of all admissions in an Australian hospital burns unit. The
      secondary objectives included examining the demographic profile, length of stay
      and co-morbidity of mental illness in these cases compared with the total
      admissions to the burns unit. METHODS: A retrospective study of medical records
      was conducted at a tertiary burns unit over a 5-year period. RESULTS: A total of
      33 self-inflicted burn injury cases were identified which represented 2.2% of all
      burns unit admissions. These patients were 70% male, the average age was 36.1
      years and 11 were born overseas, which was similar to the profile of all
      admissions. Twenty-four (73%) patients were diagnosed with a mental illness,
      compared with 14% for all admissions. The average length of stay was 52 days,
      compared with the burns unit average of 12 days. CONCLUSIONS: While the
      percentage of self-inflicted burn cases of all burns unit admissions was low,
      these cases have a greater burden of care due to their longer admission time and
      higher frequency of co-morbid mental illness. This finding supports the need for
      close involvement of consultation liaison psychiatry teams within a burns unit.

PMID- 24871970
TI  - Suicide risk categorisation of psychiatric inpatients: what it might mean and why
      it is of no use.
AB  - OBJECTIVE: Existing suicide risk assessment policies and guidelines do not
      specify whether the risk to be assessed is absolute, relative to other patients
      or relative to the same patient at an earlier time. METHODS: We utilised the
      results of a recent study of inpatient suicide to explore the implications of
      each of the above types of risk. RESULTS: No interpretation of the current
      requirements for suicide risk categorisation of psychiatric inpatients can lead
      to information that might usefully guide clinical decision-making. CONCLUSIONS:
      Policies and guidelines requiring suicide risk categorisation of inpatients
      should be withdrawn. The College should delete the mandatory entrustable
      professional activity requiring risk assessment.

PMID- 24871966
TI  - Updates in medical and surgical therapies for Tourette syndrome.
AB  - Tourette syndrome is a complex neurobehavioral disorder defined by multiple motor
      and at least 1 vocal tic, persisting over 1 year, waxing and waning in severity,
      and not explained by another condition. The condition may range from mild
      nuisance to debilitating and disabling in severity. Management includes
      counseling and reassurance, behavioral interventions, pharmacologic, and rarely,
      surgical interventions. Traditionally, alpha-2 agonists and dopamine receptor
      antagonists have been utilized. In addition, a number of different
      pharmacotherapies have been implemented in the search for improved management of
      tics with better tolerability. In rare, severely disabling cases, neuromodulation
      with deep brain stimulation may be indicated. Optimal brain targets and candidate
      selection are still in evolution. This article will review the evidence for
      current medical and surgical therapies with a focus on recent updates. 

PMID- 24871971
TI  - Genotype-phenotype correlations for infants and children with ABCA3 deficiency.
AB  - RATIONALE: Recessive mutations in the ATP-binding cassette transporter A3 (ABCA3)
      cause lethal neonatal respiratory failure and childhood interstitial lung
      disease. Most ABCA3 mutations are private. OBJECTIVES: To determine genotype
      phenotype correlations for recessive ABCA3 mutations. METHODS: We reviewed all
      published and unpublished ABCA3 sequence and phenotype data from our prospective
      genetic studies of symptomatic infants and children at Washington and Johns
      Hopkins Universities. Mutations were classified based on their predicted
      disruption of protein function: frameshift and nonsense mutations were classified
      as "null," whereas missense, predicted splice site mutations, and
      insertion/deletions were classified as "other." We compared age of presentation
      and outcomes for the three genotypes: null/null, null/other, and other/other.
      MEASUREMENTS AND MAIN RESULTS: We identified 185 infants and children with
      homozygous or compound heterozygous ABCA3 mutations and lung disease. All of the
      null/null infants presented with respiratory failure at birth compared with 75%
      of infants with null/other or other/other genotypes (P = 0.00011). By 1 year of
      age, all of the null/null infants had died or undergone lung transplantation
      compared with 62% of the null/other and other/other children (P < 0.0001).
      CONCLUSIONS: Genotype-phenotype correlations exist for homozygous or compound
      heterozygous mutations in ABCA3. Frameshift or nonsense ABCA3 mutations are
      predictive of neonatal presentation and poor outcome, whereas missense, splice
      site, and insertion/deletions are less reliably associated with age of
      presentation and prognosis. Counseling and clinical decision making should
      acknowledge these correlations.

PMID- 24871973
TI  - Paenibacillus cucumis sp. nov. isolated from greenhouse soil.
AB  - Strain CO 4-7(T) was isolated from greenhouse soil used for cultivation of
      cucumbers in Korea. The 16S rRNA gene sequence of strain CO 4-7(T) showed the
      highest sequence similarity with Paenibacillus contaminans CKOBP-6(T) (94.2%)
      among the type strains. Strain CO 4-7(T) was a strictly aerobic, Gram-staining
      positive, endospore-forming, and motile rodshaped bacterium. Strain CO 4-7(T)
      grew at 10-45 degrees C (optimum, 30 degrees C), at pH 6.0-7.5 (optimum, pH 6.5)
      and in the presence of 0-5% NaCl (optimum, 0.5%). The DNA G+C content of strain
      CO 4-7(T) was 48.5 mol%. It contained MK-7 as the major isoprenoid quinone and
      anteiso-C15:0 (51.8%), C16:0 (12.7%), and iso-C16:0 (8.6%) as the major fatty
      acids. The cell wall contained meso-diaminopimelic acid. Based on evidence from
      our polyphasic taxonomic study, it was concluded that strain CO 4-7T should be
      classified as a novel species of the genus Paenibacillus, for which, the name
      Paenibacillus cucumis sp. nov. is proposed. The type strain is CO 4-7(T) (=KACC
      17444(T)=JCM 19515(T)). 

PMID- 24871974
TI  - Prediction of bacterial microRNAs and possible targets in human cell
      transcriptome.
AB  - Recent studies have examined gene transfer from bacteria to humans that would
      result in vertical inheritance. Bacterial DNA appears to integrate into the human
      somatic genome through an RNA intermediate, and such integrations are detected
      more frequently in tumors than normal samples and in RNA than DNA samples. Also,
      vertebrate viruses encode products that interfere with the RNA silencing
      machinery, suggesting that RNA silencing may indeed be important for antiviral
      responses in vertebrates. RNA silencing in response to virus infection could be
      due to microRNAs encoded by either the virus or the host. We hypothesized that
      bacterial expression of RNA molecules with secondary structures is potentially
      able to generate miRNA molecules that can interact with the human host mRNA
      during bacterial infection. To test this hypothesis, we developed a pipeline
      based bioinformatics approach to identify putative micro-RNAs derived from
      bacterial RNAs that may have the potential to regulate gene expression of the
      human host cell. Our results suggest that 68 bacterial RNAs predicted from 37
      different bacterial genomes have predicted secondary structures potentially able
      to generate putative microRNAs that may interact with messenger RNAs of genes
      involved in 47 different human diseases. As an example, we examined the effect of
      transfecting three putative microRNAs into human embryonic kidney 293 (HEK293)
      cells. The results show that the bacterially derived microRNA sequence can
      significantly regulate the expression of the respective target human gene. We
      suggest that the study of these predicted microRNAs may yield important clues as
      to how the human host cell processes involved in human diseases like cancer,
      diabetes, rheumatoid arthritis, and others may respond to a particular bacterial
      environment.

PMID- 24871975
TI  - Diversity of extended-spectrum and plasmid-mediated AmpC beta-lactamases in
      Enterobacteriaceae isolates from Portuguese health care facilities.
AB  - A group of 124 Enterobacteriaceae isolates resistant to third generation
      cephalosporins, and collected in distinct health care facilities of different
      Portuguese regions was analysed. The great majority of the isolates were also
      resistant to fourth generation cephalosporins (83.9%), monobactam (96%),
      amoxicillin plus clavulanic acid (85.5%), and piperacillin plus tazobactam
      (66.9%). Overall, 84.7% (105/124) were multidrug resistant. Molecular methods
      enabled us to identify 86.3% (107/124) extended-spectrum beta-lactamases (ESBL)
      producers, revealing a diversity of class A beta-lactamases from different
      families, like TEM (TEM-1, TEM-10, TEM-24, and TEM-52), SHV (SHV-1, SHV-12, and
      SHV-28), CTX-M (CTX-M-1, CTX-M-9, CTX-M-14, CTX-M-15, and CTXM-32), and GES (GES
      1). We have also detected class C enzymes like plasmid-mediated AmpC beta
      lactamases (PMAbetas, DHA-1, and CMY-2) and chromosomal AmpCs in Enterobacter and
      Citrobacter spp. The PMAbeta genetic context mapping suggests association with
      mobile elements, plasmid importation and the potential emergence of these beta
      lactamases. The most prevalent beta-lactamase detected was CTX-M-15 (66.1%) and
      in 41.1% of the isolates it was associated with TEM-, OXA-type beta-lactamases
      and Aac(6)?Ib-cr, which might indicate that the respective genotype has settled
      in our country. Indeed, CTX-M-15 was distributed amongst distinct clinical
      settings of several health care facilities (93.5%) from various regions. We
      provide evidence of a concerning clinical situation that includes vast occurrence
      of ESBLs, the settling of CTX-M beta-lactamases, and the report of plasmidic and
      chromosomal AmpC in Portugal. 

PMID- 24871972
TI  - The role of microRNAs in hepatitis C virus replication and related liver
      diseases.
AB  - Hepatitis C virus (HCV) infection is a worldwide health problem and is one of the
      main causes of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma
      (HCC). However, only limited therapeutic options and no vaccines are currently
      available against HCV infection. Recent studies of microRNAs (miRNAs), which are
      able to regulate HCV replication and its related liver diseases by directly
      interacting with the HCV genome or indirectly controlling virus-associated host
      pathways, have broadened our understanding of the HCV life cycle. HCV utilizes
      host cellular miRNAs and modulates expression of miRNAs in infected hepatocytes
      for its infection and propagation. Moreover, such miRNAs directly or indirectly
      alter HCV replication efficiency and induce liver diseases including liver
      fibrosis, cirrhosis, or HCC. Representatively, miR-122 directly modulates the HCV
      life cycle by increasing HCV translation and genomic RNA stability. Recently, a
      phase IIa clinical trial with miravirsen, an LNA form of antimiR-122
      oligonucleotides, showed significant reduction in serum HCV levels in patients
      chronically infected with HCV with no detectible evidence of resistance. In
      addition to miR-122, other miRNAs involved in the regulation of HCV propagation
      could be targeted in strategies to modulate HCV replication and pathogenesis. In
      this review, we summarize the features of miRNAs critical for HCV replication and
      HCV-mediated liver abnormalities and briefly discuss their potential application
      as therapeutic reagents for the treatment of HCV infection and its related
      diseases. 

PMID- 24871976
TI  - Profiling of the bacteria responsible for pyogenic liver abscess by 16S rRNA gene
      pyrosequencing.
AB  - Pyogenic liver abscess (PLA) is a severe disease with considerable mortality and
      is often polymicrobial. Understanding the pathogens that cause PLA is the basis
      for PLA treatment. Here, we profiled the bacterial composition in PLA fluid by
      pyrosequencing the 16S ribosomal RNA (rRNA) gene based on next-generation
      sequencing (NGS) technology to identify etiological agents of PLA and to provide
      information of their 16S rRNA sequences for application to DNA-based techniques
      in the hospital. Twenty patients with PLA who underwent percutaneous catheter
      drainage, abscess culture, and blood culture for isolates were included. Genomic
      DNAs from abscess fluids were subjected to polymerase chain reaction and
      pyrosequencing of the 16S rRNA gene with a 454 GS Junior System. The abscess and
      blood cultures were positive in nine (45%) and four (20%) patients, respectively.
      Pyrosequencing of 16S rRNA gene showed that 90% of the PLA fluid samples
      contained single or multiple genera of known bacteria such as Klebsiella,
      Fusobacterium, Streptococcus, Bacteroides, Prevotella, Peptostreptococcus,
      unassigned Enterobacteriaceae, and Dialister. Klebsiella was predominantly found
      in the PLA fluid samples. All samples that carried unassigned bacteria had 26.8%
      reads on average. We demonstrated that the occurrence of PLA was associated with
      eight known bacterial genera as well as unassigned bacteria and that 16S rRNA
      gene sequencing was more useful than conventional culture methods for accurate
      identification of bacterial pathogens from PLA. 

PMID- 24871977
TI  - Altered mRNA levels of MOV10, A3G, and IFN-alpha in patients with chronic
      hepatitis B.
AB  - To explore the relationship of the MOV10, A3G, and IFN-alpha mRNA levels with
      chronic hepatitis B virus (HBV) infection, Blood samples from 96 patients with
      chronic hepatitis B (CHB) and 21 healthy individuals as control were collected.
      HBV DNA load and aminotransferase in the serum were tested using real time PCR
      and velocity methods, respectively. The MOV10, A3G, and IFN-alpha mRNA levels in
      the peripheral blood mononuclear cells (PBMC) were examined through qRT-PCR. The
      MOV10, A3G, and IFN-alpha mRNA levels in CHB group was significantly lower than
      those in the control group (P<0.01, P<0.05, P<0.01, respectively). The A3G mRNA
      level in the high-HBV DNA load group was lower than that in the low-HBV DNA load
      group (P<0.05). However, no statistical difference was found in the MOV10 and IFN
      alpha mRNA levels between the two HBV DNA load groups. Furthermore, the MOV10
      mRNA level showed positive correlation with IFN-alpha in the control group. These
      results indicated that the expression of the innate immune factors MOV10, A3G,
      and IFN-alpha is affected by chronic HBV infection. 

PMID- 24871978
TI  - Superinfection exclusion reveals heteroimmunity between Pseudomonas aeruginosa
      temperate phages.
AB  - Temperate siphophages (MP29, MP42, and MP48) were isolated from the culture
      supernatant of clinical Pseudomonas aeruginosa isolates. The complete nucleotide
      sequences and annotation of the phage genomes revealed the overall synteny to the
      known temperate P. aeruginosa phages such as MP22, D3112, and DMS3. Genome-level
      sequence analysis showed the conservation of both ends of the linear genome and
      the divergence at the previously identified dissimilarity regions (R1 to R9).
      Protein sequence alignment of the c repressor (ORF1) of each phage enabled us to
      divide the six phages into two groups: D3112 group (D3112, MP29, MP42, and MP48)
      and MP22 group (MP22 and DMS3). Superinfection exclusion was observed between the
      phages belonging to the same group, which was mediated by the specific
      interaction between the c repressor and the cognate operator. Based on these, we
      suggest that the temperate siphophages prevalent in the clinical strains of P.
      aeruginosa represent at least two distinct heteroimmunity groups. 

PMID- 24871987
TI  - Arterial mechanical motion estimation based on a semi-rigid body deformation
      approach.
AB  - Arterial motion estimation in ultrasound (US) sequences is a hard task due to
      noise and discontinuities in the signal derived from US artifacts. Characterizing
      the mechanical properties of the artery is a promising novel imaging technique to
      diagnose various cardiovascular pathologies and a new way of obtaining relevant
      clinical information, such as determining the absence of dicrotic peak,
      estimating the Augmentation Index (AIx), the arterial pressure or the arterial
      stiffness. One of the advantages of using US imaging is the non-invasive nature
      of the technique unlike Intra Vascular Ultra Sound (IVUS) or angiography invasive
      techniques, plus the relative low cost of the US units. In this paper, we propose
      a semi rigid deformable method based on Soft Bodies dynamics realized by a hybrid
      motion approach based on cross-correlation and optical flow methods to quantify
      the elasticity of the artery. We evaluate and compare different techniques (for
      instance optical flow methods) on which our approach is based. The goal of this
      comparative study is to identify the best model to be used and the impact of the
      accuracy of these different stages in the proposed method. To this end, an
      exhaustive assessment has been conducted in order to decide which model is the
      most appropriate for registering the variation of the arterial diameter over
      time. Our experiments involved a total of 1620 evaluations within nine simulated
      sequences of 84 frames each and the estimation of four error metrics. We conclude
      that our proposed approach obtains approximately 2.5 times higher accuracy than
      conventional state-of-the-art techniques. 

PMID- 24871979
TI  - Antiviral activity of 3,4'-dihydroxyflavone on influenza a virus.
AB  - Influenza virus infection causes thousands of deaths and millions of
      hospitalizations worldwide every year and the emergence of resistance to anti
      influenza drugs has prompted scientists to seek new natural antiviral materials.
      In this study, we screened 13 different flavonoids from various flavonoid groups
      to identify the most potent antiviral flavonoid against human influenza A/PR/8/34
      (H1N1). The 3-hydroxyl group flavonoids, including 3,2?dihydroxyflavone (3,2?DHF)
      and 3,4?dihydroxyflavone (3,4?DHF), showed potent anti-influenza activity. They
      inhibited viral neuraminidase activity and viral adsorption onto cells. To
      confirm the anti-influenza activity of these flavonoids, we used an in vivo mouse
      model. In mice infected with human influenza, oral administration of 3,4?DHF
      significantly decreased virus titers and pathological changes in the lung and
      reduced body weight loss and death. Our data suggest that 3-hydroxyl group
      flavonoids, particularly 3,4?DHF, have potent antiviral activity against human
      influenza A/PR/8/34 (H1N1) in vitro and in vivo. Further clinical studies are
      needed to investigate the therapeutic and prophylactic potential of the 3
      hydroxyl group flavonoids in treating influenza pandemics. 

PMID- 24871988
TI  - Sparse representation for infrared Dim target detection via a discriminative over
      complete dictionary learned online.
AB  - It is difficult for structural over-complete dictionaries such as the Gabor
      function and discriminative over-complete dictionary, which are learned offline
      and classified manually, to represent natural images with the goal of ideal
      sparseness and to enhance the difference between background clutter and target
      signals. This paper proposes an infrared dim target detection approach based on
      sparse representation on a discriminative over-complete dictionary. An adaptive
      morphological over-complete dictionary is trained and constructed online
      according to the content of infrared image by K-singular value decomposition (K
      SVD) algorithm. Then the adaptive morphological over-complete dictionary is
      divided automatically into a target over-complete dictionary describing target
      signals, and a background over-complete dictionary embedding background by the
      criteria that the atoms in the target over-complete dictionary could be
      decomposed more sparsely based on a Gaussian over-complete dictionary than the
      one in the background over-complete dictionary. This discriminative over-complete
      dictionary can not only capture significant features of background clutter and
      dim targets better than a structural over-complete dictionary, but also
      strengthens the sparse feature difference between background and target more
      efficiently than a discriminative over-complete dictionary learned offline and
      classified manually. The target and background clutter can be sparsely decomposed
      over their corresponding over-complete dictionaries, yet couldn't be sparsely
      decomposed based on their opposite over-complete dictionary, so their residuals
      after reconstruction by the prescribed number of target and background atoms
      differ very visibly. Some experiments are included and the results show that this
      proposed approach could not only improve the sparsity more efficiently, but also
      enhance the performance of small target detection more effectively. 

PMID- 24871989
TI  - Calculation of target-specific point distribution for 2D mobile laser scanners.
AB  - The current generation of Mobile Mapping Systems (MMSs) capture high density
      spatial data in a short time-frame. The quantity of data is difficult to predict
      as there is no concrete understanding of the point density that different scanner
      configurations and hardware settings will exhibit for objects at specific
      distances. Obtaining the required point density impacts survey time, processing
      time, data storage and is also the underlying limit of automated algorithms. This
      paper details a novel method for calculating point and profile information for
      terrestrial MMSs which are required for any point density calculation. Through
      application of algorithms utilising 3D surface normals and 2D geometric formulae,
      the theoretically optimal profile spacing and point spacing are calculated on
      targets. Both of these elements are a major factor in calculating point density
      on arbitrary objects, such as road signs, poles or buildings-all important
      features in asset management surveys. 

PMID- 24871990
TI  - External validation of the number of risk factors score in a palliative care
      outpatient clinic at a comprehensive cancer center.
AB  - BACKGROUND: Prognostic tools are available to predict if terminally ill cancer
      patients have days or weeks to live. Tools for predicting the prognosis in
      ambulatory patients at an earlier stage are lacking. The Number of Risk Factors
      (NRF) score developed in ambulatory cancer patients receiving palliative
      radiation therapy may be suitable for this purpose but has not been tested in a
      palliative care setting. OBJECTIVE: Our aim was to evaluate the prognostic
      accuracy of the NRF score in patients referred to a palliative care outpatient
      clinic at a comprehensive cancer center. METHODS: We conducted a retrospective
      chart review of NRF scores and survival in 300 consecutive, newly referred
      patients. Measurements included primary cancer type, extent of disease, Karnofsky
      Performance Scale (KPS) score, and survival duration after first visit. One point
      was allocated each for cancer other than breast cancer, metastases other than
      bone, and low KPS score. RESULTS: Of 300 patients, 236 (79%) had advanced
      disease. Of those 236, 212 (90%) had a cancer other than breast cancer, 180 (76%)
      had metastatic disease in sites other than bone, and 64 (27%) had a KPS score
      <70%. During the 2-year follow-up, 221 (94%) patients died, with overall median
      survival of 4.9 months (95% confidence interval, 3.9-6.1 months). NRF scores of 0
      to 1, 2, and 3 split the sample into subgroups with highly significantly
      different survival among the groups, with medians 9.0, 4.6, and 2.1 months,
      respectively (Wilcoxon test chi(2)=43.9, degrees of freedom [df] 2, p<0.0001). A
      simple parametric model was fit to determine the probability of subgroup members
      surviving to a certain number of months. CONCLUSIONS: In cancer patients referred
      to palliative care earlier in their disease trajectory, the NRF score may be a
      useful prognostic tool. Further validation in other palliative care populations
      is needed.

PMID- 24871993
TI  - Cardiorespiratory fitness levels among U.S. youth aged 12-15 years: United
      States, 1999-2004 and 2012.
AB  - Data from the National Health and Nutrition Examination Survey (NHANES), 1999
      2004 and the NHANES National Youth Fitness Survey, 2012 In 2012, about 42% of
      U.S. youth aged 12-15 years had adequate levels of cardiorespiratory fitness. The
      percentage of youth who had adequate levels of cardiorespiratory fitness did not
      differ by race and Hispanic origin, or by family income-to-poverty ratio. The
      percentage of youth who had adequate levels of cardiorespiratory fitness
      decreased as weight status increased. The percentage of youth aged 12-15 who had
      adequate levels of cardiorespiratory fitness decreased from 52.4% in 1999-2000 to
      42.2% in 2012. Physical fitness has been defined as "a set of attributes that
      people have or achieve that relates to the ability to perform physical activity"
      (1). Cardiorespiratory fitness is one component of physical fitness and is
      defined as the "ability of the circulatory and respiratory systems to supply fuel
      during sustained physical activity and to eliminate fatigue products after
      supplying fuel" (1). Cardiorespiratory fitness is most often measured by maximal
      oxygen uptake (VO2max), which is the maximum capacity of the body to transport
      and use oxygen during physical activity (2). This report presents the most recent
      national data on the percentage of youth who had adequate levels of
      cardiorespiratory fitness. Adequate levels of cardiorespiratory fitness are based
      on standards that are age- and sex-specific and established based on how fit
      children need to be for good health.

PMID- 24871991
TI  - Design, characterization and expression of a novel hybrid peptides melittin (1
      13)-LL37 (17-30).
AB  - Hybridizing of different antimicrobial peptides (AMPs) has been a common practice
      for obtaining novel hybrid AMPs with elevated antibacterial activity but
      minimized cytotoxicity. The hybrid peptides melittin (1-13)-LL37 (17-30) (M-L)
      combining the hydrophobic N-terminal fragment of melittin (M) with the core
      antibacterial fragment of LL37 (L), was designed for the first time to explore
      its antibacterial activity and hemolytic activity against bacteria and sheep
      erythrocyte respectively. Results showed that M-L had an even more potent
      antibacterial activity against all indicator strains (especially gram-positive
      bacteria) than M and L, whereas didn't exhibit hemolytic activity to sheep
      erythrocytes, implying M-L can be served as a potential therapeutic drug to
      substitute traditional antibiotics. However the high expense of biosynthesis
      limited its further research, therefore fusion expression of M-L was carried out
      in Escherichia coli (E. coli) for overproducing the hybrid peptide so as to solve
      the problem. The DNA sequence encoding M-L with preferred codons was cloned into
      the pET-SUMO vector for protein expression in E. coli BL21 (DE3). After IPTG
      induction, approximately 165 mg soluble fusion protein SUMO-M-L was recovered per
      liter supernatant of the fermentation ultrasonic lysate using Ni-NTA Sepharose
      column (92 % purity). And 23 mg recombinant M-L was obtained per liter culture
      after cleavage of SUMO protease and purification of Ni-NTA Sepharose column. In
      sum, this research not only supplied an effective approach for overproducing
      hybrid peptide M-L, but paved the way for its further exploration on
      pharmaceutical potential and medical importance.

PMID- 24871994
TI  - Palladium-catalyzed formal arylacylation of allenes employing acid chlorides and
      arylboronic acids.
AB  - Palladium-catalyzed formal arylacylation of allenes using acid chlorides and
      arylboronic acids has been achieved. The reaction afforded the corresponding
      alpha,beta-unsaturated ketones regio- and stereoselectively. 

PMID- 24871992
TI  - The role of bronchial epithelial cell apoptosis in the pathogenesis of COPD.
AB  - There is an increased airway inflammation in the pathogenesis of chronic
      obstructive pulmonary disease (COPD), and it has been suggested that there may
      also be problem in the apoptosis and renewal of cells. However, there are limited
      human airway cell studies, in particular those from larger airways such as
      bronchi. We cultured primary human bronchial epithelial cells (HBECs) from
      bronchial explants of smokers (n = 6) without COPD and smokers with COPD (n = 8).
      Apoptosis was studied by fluorescence activated cell sorting. qRT-PCR was used to
      assess mRNA expression for proteins involving apoptosis including p21(CIP1/WAF1),
      p53, caspase-8 and caspase-9. Although there was no difference in the rate of
      viable cells between cells from smokers and COPDs, the level of early apoptotic
      cells was significantly increased in COPD cells [mean +/- standard error of mean
      (SEM) = 4.86 +/- 3.2 %, p = 0.015] as compared to smokers (mean +/- SEM = 2.71 +/
      1.62 %). In contrast, the rate of late apoptotic cells was significantly
      decreased in COPD cells (mean +/- SEM = 9.82 +/- 5.71 %) comparing to smokers
      (mean +/- SEM = 15.21 +/- 5.08 %, p = 0.003). Although expression of mRNA for
      p21(CIP1/WAF1) and caspase-9 was similar in both groups, p53 and caspase-8 mRNA
      expression was significantly greater in COPD cells. These findings suggest that
      HBEC apoptosis is increased in COPD, and that this involves p53 and caspase-8
      pathways.

PMID- 24871995
TI  - Synthesis and structure-activity relationship studies in serotonin 5-HT4 receptor
      ligands based on a benzo[de][2,6]naphthridine scaffold.
AB  - A small series of serotonin 5-HT4 receptor ligands has been designed from
      flexible 2-methoxyquinoline compounds 7a,b by applying the conformational
      constraint approach. Ligands 7a,b and the corresponding conformationally
      constrained analogues 8a-g were synthesized and their interactions with the 5-HT4
      receptor were examined by measuring both binding affinity and the ability to
      promote or inhibit receptor-G protein coupling. Ester derivative 7a and
      conformationally constrained compound 8b were demonstrated to be the most
      interesting compounds showing a nanomolar 5-HT4R affinity similar to that shown
      by reference ligands cisapride (1) and RS-23,597-190 (4). The result was
      rationalized by docking studies in term of high similarity in the binding
      modalities of flexible 7a and conformationally constrained 8b. The intrinsic
      efficacy of some selected ligands was determined by evaluating the receptor-G
      protein coupling and the results obtained demonstrated that the nature and the
      position of substituents play a critical role in the interaction of these ligands
      with their receptor. 

PMID- 24871997
TI  - The syntheses of alpha-ketoamides via(n)Bu4NI-catalyzed multiple sp(3)C-H bond
      oxidation of ethylarenes and sequential coupling with dialkylformamides.
AB  - The (n)Bu4NI-catalyzed sequential C-O and C-N bond formation via multiple sp(3)C
      H bond activation of ethylarenes, using N,N-dialkylformamide as the amino source,
      provided alpha-ketoamides with moderate yields. 

PMID- 24871998
TI  - Introducing new vitreous cutter blade shapes: a fluid dynamics study.
AB  - PURPOSE: To assess the efficacy of novel vitreous cutter blades compared with the
      regular guillotine by means of particle image velocimetry. Tested blades included
      a regular blade (RB) and newer designs where a circular (hole blade [HB]) or a
      slit aperture (slit blade [SB]) had been opened proximal to the cutting edge.
      METHODS: Twenty-three-gauge probes were immersed in BSS or egg albumen, and high
      speed video (1,000 frames per second) was recorded. Duty cycle, flow rate, and
      acceleration generated by Venturi and peristaltic pumps were measured under
      cutter settings simulating "low-speed" vitrectomy (1600 cuts per minute, 200 mmHg
      vacuum) and "high speed" vitrectomy (3000 cuts per minute, 300 mmHg vacuum).
      RESULTS: The SB and HB had a significantly more favorable duty cycle than that of
      the RB (P < 0.01) and higher BSS flow rate regardless of the aspiration. The SB
      flow rate in albumen was significantly higher than that of the HB and RB only
      over 1,000 cuts per minute using a peristaltic pump and at any cut rate with
      Venturi pump (P < 0.001). The SB also yielded the lowest fluid acceleration than
      both the HB and SB (P < 0.001 in all cases). CONCLUSION: The HB and SB proved to
      be significantly more efficient than the RB, with better duty cycle and higher
      flow rate. The SB generated significantly less fluid acceleration than any other
      tested blade, regardless of the fluid viscosity and pump technology. The SB
      design is significantly more efficient and possibly safer than both HB and RB.

PMID- 24871996
TI  - Carbonic anhydrase inhibitors. Synthesis of a novel series of 5-substituted 2,4
      dichlorobenzenesulfonamides and their inhibition of human cytosolic isozymes I
      and II and the transmembrane tumor-associated isozymes IX and XII.
AB  - A series of novel 5-substituted 2,4-dichlorobenzenesulfonamides 5a-c, 6a-d, 7a-j
      and 10a-i have been synthesized and investigated as inhibitors of four isoforms
      of zinc enzyme carbonic anhydrase (CA.EC 4.2.1.1), that is the cytosolic CA I and
      II, and tumor-associated isozymes CA IX and XII. Against the human CA I
      investigated compounds displayed KI values from 349 to 7355 nM, toward hCA II at
      range of 6.9 to 164 nM, while against hCA IX ranging from 2.8 to 76 nM and
      against hCA XII in the range of 2.7 to 95 nM. The excellent inhibitory activity
      against tumor-associated hCA IX was found. The twenty one new compounds displayed
      a powerful inhibitory potency toward hCA IX (KI = 2.8-21.7 nM) in comparison with
      the clinically used CAIs AAZ, MZA, EZA, DCP and IND (24-50 nM). Among them the
      most potent hCA IX inhibitor 7b (KI = 2.8 nM) was 8.5-fold stronger than IND (KI
      = 24 nM). Toward tumor-associated hCA XII compounds 6c and 10a (KI = 2.7 and 2.8
      nM, respectively) showed a better inhibitory potency than reference sulfonamides
      MZA and IND (KI = 3.4 nM).

PMID- 24872001
TI  - Solid-state emission enhancement in vaulted trans
      bis(salicylaldiminato)platinum(II) crystals with halogen functionality.
AB  - The synthesis, structure, and solid-state emission of vaulted trans
      bis(salicylaldiminato)platinum(ii) complexes 1-3 with halogen functionalities are
      described and compared with the non-substituted analogues. Chloro-substitution
      provided an improvement of the low emission properties of short-vaulted, non
      substituted complexes 1 and 2 in the crystalline state at ambient temperature,
      while the intense emission of long-vaulted analogues 3 remained unchanged. Bromo
      substituted crystals also emit intensively, while the fluoro analogue is non
      emissive under the same conditions. Temperature-dependent emission spectra
      indicate that all chloro- and bromo-substituted crystals with enhanced emission
      properties at ambient temperature exhibit improved heat resistance properties
      towards emission decay with the halogen functionalities. X-ray diffraction
      studies revealed that such a positive effect of halogenation for the enhancement
      of solid-state emission is due to significant molecular constraints in the
      crystals by a combination of the vaulted structure and three-dimensional HX
      hydrogen bonding interactions. 

PMID- 24872002
TI  - Single-dose gadobutrol in comparison with single-dose gadobenate dimeglumine for
      magnetic resonance imaging of chronic myocardial infarction at 3 T.
AB  - OBJECTIVES: The aim of this study was to compare the contrast-to-noise ratio
      (CNR) values of infarct and remote myocardium as well as infarct and blood after
      application of 0.1 mmol/kg gadobutrol and 0.1 mmol/kg gadobenate dimeglumine on
      late gadolinium enhancement magnetic resonance (MR) images. MATERIAL AND METHODS:
      The study was a prospective randomized controlled clinical study. After informed
      consent was obtained, 20 patients (12 men, 8 women; mean age, 67 +/- 11 years)
      with known chronic myocardial infarction were included for an intraindividual
      comparison of a single-dose gadobutrol and a single-dose gadobenate dimeglumine.
      Two MR imaging examinations were performed within a period of 28 days in a
      crossover design. Late gadolinium enhancement imaging was performed 10 minutes
      after gadolinium administration using a 2-dimensional phase-sensitive inversion
      recovery gradient echo sequence at 3 T. Infarct size, signal intensities (SIs),
      signal-to-noise ratio, and CNR were determined on phase-sensitive MR images.
      Values for CNR were calculated as CNRinfarct/myocardium = (SIinfarct -
      SImyocardium)/SDnoise and CNRinfarct/blood = (SIinfarct - SIblood)/SDnoise. In
      addition, the areas of myocardial infarction were determined on single slices.
      The entire infarct volumes were calculated by adding the areas with
      hyperenhancement multiplied by the slice thickness. RESULTS: Late gadolinium
      enhancement was present in all patients. Median values of the infarct area,
      infarct volume, and transmurality for gadobutrol and gadobenate dimeglumine
      showed good to excellent concordance (rc = 0.85, rc = 0.95, and rc = 0.71,
      respectively). The mean signal-to-noise ratio values for infarct, remote
      myocardium, and ventricular blood were 18.6 +/- 6.5, 4.1 +/- 3.7, and 14.6 +/-
      7.5, respectively, for gadobutrol and 18.8 +/- 8.9, 4.9 +/- 4.5, and 17.8 +/-
      10.1, respectively, for gadobenate dimeglumine (P = 0.93, P = 0.48, and P =
      0.149, respectively). The mean values of CNRinfarct/myocardium and
      CNRinfarct/blood were 14.5 +/- 5.9 and 4.0 +/- 4.6, respectively, for gadobutrol
      and 13.9 +/- 6.1 and 0.9 +/- 4.5, respectively, for gadobenate dimeglumine (P =
      0.69 and P = 0.02, respectively). CONCLUSION: Both gadobutrol and gadobenate
      dimeglumine allow for successful late gadolinium enhancement imaging of chronic
      myocardial infarction after a single-dose application (0.1 mmol/kg) at 3 T.
      Gadobutrol provides a higher CNR between infarct and blood. The CNRs between
      infarct and normal myocardium, infarct size, and transmural extent were similar
      for both contrast agents.

PMID- 24872004
TI  - Magnetic resonance imaging for noninvasive assessment of lung fibrosis onset and
      progression: cross-validation and comparison of different magnetic resonance
      imaging protocols with micro-computed tomography and histology in the bleomycin
      induced mouse model.
AB  - OBJECTIVES: Bleomycin instillation is frequently used to model lung fibrosis,
      although the onset and severity of pathology varies highly between mice. This
      makes non-invasive fibrosis detection and quantification essential to obtain a
      comprehensive analysis of the disease course and to validate novel therapies.
      Magnetic resonance imaging (MRI) of lung disease progression and therapy may
      provide such a sensitive in vivo readout of lung fibrosis, bypassing
      radiotoxicity concerns (when using micro-CT [MUCT]) and elaborate invasive end
      point measurements (histology). We aimed to optimize and evaluate 3 different
      lung MRI contrast and acquisition methods to visualize disease onset and
      progression in the bleomycin-induced mouse model of lung fibrosis using a small
      animal MRI scanner. For validation, we compared the MRI results with established
      MUCT and histological measures of lung fibrosis. MATERIALS AND METHODS: Free
      breathing bleomycin-instilled and control mice were scanned in vivo with
      respiration-triggered conventional, ultrashort echo time and self-gated MRI pulse
      sequences (9.4 T) and MUCT at baseline and weekly at days 7, 14, 21, and 28 after
      bleomycin instillation. After the last imaging time point, the mice were killed
      and the lungs were isolated for criterion standard histological analysis of lung
      fibrosis and quantification of lung collagen content for validation of the
      imaging results. The agreement between quantitative MRI and MUCT data and
      standard measurements was analyzed by linear regression. RESULTS: All 3 MRI
      protocols were able to visualize and quantify lung pathology onset and
      progression in individual bleomycin-instilled mice. In vivo MRI results were in
      excellent agreement with in vivo MUCT and criterion standard histological
      measures of lung fibrosis. Ultrashort echo time MRI appeared particularly useful
      for detecting early disease; self-gated MRI, for improved breathing motion
      handling. DISCUSSION: Magnetic resonance imaging sensitively visualizes and
      quantifies lung fibrosis in vivo, which makes it a noninvasive, translatable,
      safe, and potentially more versatile alternative to invasive methods or MUCT,
      thereby stimulating pathogenesis and preclinical research.

PMID- 24872003
TI  - Efficacy of preventive interventions for iodinated contrast-induced acute kidney
      injury evaluated by intrarenal oxygenation as an early marker.
AB  - OBJECTIVE: The objective of this study was to evaluate the effects of potential
      renoprotective interventions such as the administration of N-acetylcysteine (NAC;
      antioxidant) and furosemide (diuretic) on intrarenal oxygenation as evaluated by
      blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) in
      combination with urinary neutrophil gelatinase-associated lipocalin (NGAL)
      measurements. MATERIALS AND METHODS: Rats received nitric oxide synthase
      inhibitor L-NAME (10 mg/kg) and cyclooxygenase inhibitor indomethacin (10 mg/kg)
      to induce the risk for developing iodinated contrast-induced acute kidney injury
      before receiving one of the interventions: NAC, furosemide, or placebo. One of
      the 3 iodinated contrast agents (iohexol, ioxaglate, or iodixanol) was then
      administered (1600-mg organic iodine per kilogram body weight). Fifty-four
      Sprague-Dawley rats were allocated in a random order into 9 groups on the basis
      of the intervention and the contrast agent received.Blood-oxygen-level-dependent
      MRI-weighted images were acquired on a Siemens 3.0-T scanner using a multiple
      gradient recalled echo sequence at baseline, after L-NAME, indomethacin,
      interventions or placebo, and iodinated contrast agents. Data acquisition and
      analysis were performed in a blind fashion. R2* (=1/T2*) maps were generated
      inline on the scanner. A mixed-effects growth curve model with first-order
      autoregressive variance-covariance was used to analyze the temporal data. Urinary
      NGAL, a marker of acute kidney injury, was measured at baseline, 2 and 4 hours
      after the contrast injection. RESULTS: Compared with the placebo-treated rats,
      those treated with furosemide showed a significantly lower rate of increase in
      R2* (P < 0.05) in the renal inner stripe of the outer medulla. The rats treated
      with NAC showed a lower rate of increase in R2* compared with the controls, but
      the difference did not reach statistical significance. Urinary NGAL showed little
      to no increase in R2* after administration of iodixanol in the rats pretreated
      with furosemide but demonstrated significant increase in the rats pretreated with
      NAC or placebo (P < 0.05). CONCLUSIONS: This is the first study to evaluate the
      effects of interventions to mitigate the deleterious effects of contrast media
      using BOLD MRI. The rate of increase in R2* after administration of iodinated
      contrast is associated with acute renal injury as evaluated by NGAL. Further
      studies are warranted to determine the optimum dose of furosemide and NAC for
      mitigating the ill effects of contrast media. Because NGAL has been shown to be
      useful in humans to document iodinated contrast-induced acute kidney injury, the
      method presented in this study using BOLD MRI and NGAL measurements can be
      translated to humans.

PMID- 24872005
TI  - Radiation exposure of contrast-enhanced spectral mammography compared with full
      field digital mammography.
AB  - OBJECTIVES: Contrast-enhanced spectral mammography (CESM) shows promising initial
      results but comes at the cost of increased dose as compared with full-field
      digital mammography (FFDM). We aimed to quantitatively assess the dose increase
      of CESM in comparison with FFDM. MATERIALS AND METHODS: Radiation exposure
      related data (such as kilovoltage, compressed breast thickness, glandularity,
      entrance skin air kerma (ESAK), and average glandular dose (AGD) were retrieved
      for 47 CESM and 715 FFDM patients. All examinations were performed on 1
      mammography unit. Radiation dose values reported by the unit were validated by
      phantom measurements. Descriptive statistics of the patient data were generated
      using a statistical software package. RESULTS: Dose values reported by the
      mammography unit were in good qualitative agreement with those of phantom
      measurements. Mean ESAK was 10.5 mGy for a CESM exposure and 7.46 mGy for an FFDM
      exposure. Mean AGD for a CESM exposure was 2.80 mGy and 1.55 mGy for an FFDM
      exposure. CONCLUSIONS: Compared with our institutional FFDM, the AGD of a single
      CESM exposure is increased by 1.25 mGy (+81%), whereas ESAK is increased by 3.07
      mGy (+41%). Dose values of both techniques meet the recommendations for maximum
      dose in mammography.

PMID- 24872006
TI  - Virtual monoenergetic dual-energy computed tomography: optimization of
      kiloelectron volt settings in head and neck cancer.
AB  - OBJECTIVES: The aim of this study was to evaluate the effects on objective and
      subjective image quality of virtual monoenergetic reconstructions at various
      energy levels of dual-energy computed tomography (DECT) in patients with head and
      neck cancer. MATERIALS AND METHODS: We included 71 (53 men, 18 women; age, 59.3
      +/- 12.0 years; range, 33-90 years) patients with biopsy-proven untreated primary
      (n = 55) or recurrent (n = 16) squamous cell carcinoma who underwent head and
      neck DECT. Images were reconstructed with a linear blending setting emulating 120
      kV acquisition (M_0.3; 30% of 80 kV, 70% of 140 kV spectrum) and as virtual
      monoenergetic images with photon energies of 40, 60, 80, and 100 keV. Attenuation
      of lesion, various anatomic landmarks, and image noise were objectively measured,
      and lesion contrast-to-noise ratio (CNR) was calculated. Two independent blinded
      radiologists subjectively rated each image series using a 5-point grading scale
      regarding overall image quality, lesion delineation, image sharpness, and image
      noise. RESULTS: Tumor attenuation peaked at 40 keV (140.2 +/- 42.6 HU) followed
      by the 60 keV (121.7 +/- 25.5 HU) and M_0.3 series (102.7 +/- 22.3; all P <
      0.001). However, the calculated lesion CNR was highest in the 60 keV
      reconstructions (12.45 +/- 7.17), 80 keV reconstructions (8.66 +/- 6.58), and
      M_0.3 series (5.21 +/- 3.15; all P < 0.001) and superior to the other
      monoenergetic series (all P < 0.001). Subjective image analysis was highest for
      the 60 keV series regarding overall image quality (4.22; kappa = 0.411) and
      lesion delineation (4.35; kappa = 0.459) followed by the M_0.3 series (3.81;
      kappa = 0.394; 3.77; kappa = 0.451; all P < 0.001). Image sharpness showed no
      significant difference between both series (3.81 vs 3.79; P = 0.78). Image noise
      was rated superior in the 80 and 100 keV series (4.31 vs 4.34; P = 0.522).
      CONCLUSIONS: Compared with linearly blended images, virtual monoenergetic
      reconstructions of DECT data at 60 keV significantly improve lesion enhancement
      and CNR, subjective overall image quality, and tumor delineation of head and neck
      squamous cell carcinoma.

PMID- 24872007
TI  - Progressive increase of T1 signal intensity of the dentate nucleus on unenhanced
      magnetic resonance images is associated with cumulative doses of intravenously
      administered gadodiamide in patients with normal renal function, suggesting
      dechelation.
AB  - OBJECTIVES: The purpose of this study was to assess the association between the
      serial number of gadolinium-enhanced magnetic resonance imaging (MRI)
      examinations and the signal hyperintensity of the dentate nucleus on unenhanced
      T1-weighted images in patients with multiple sclerosis (MS) and those with brain
      metastases (BMs). MATERIALS AND METHODS: A group of 38 patients with MS and 37
      patients with BM who had undergone at least 2 consecutive enhanced MRI
      examinations in our institution were examined for this retrospective
      observational study. The average T1 signal intensity of the dentate nuclei and
      the pons was obtained, and the dentate nuclei-to-pons (DNP) signal intensity
      ratio was calculated. These values were compared between patients with less than
      6 and 6 enhanced MRI scans or more (eMRI). Relative changes of the DNP were
      plotted against the number of enhanced MRI scans (eMRIn). RESULTS: A progressive
      increase in the T1 signal intensity of the DNP ratio was observed both in the MS
      group and in the BM group. The DNP ratios of the last eMRI scans in the subgroup
      of patients with 6 eMRI scans or more were significantly higher than those of the
      first eMRI scan in the MS group (P < 0.001) and in the BM group (P < 0.01).
      Relative changes of the DNP showed a positive correlation with the eMRIn with a
      Spearman rho of 0.96 (P < 0.001) in the MS group and that of 0.88 (P < 0.001) in
      the BM group. Curve regression analyses of the relative change of DNP ratios
      showed linear models to best fit the data with r(2) of 0.89 in the MS group and
      r(2) of 0.74 in the BM group. CONCLUSIONS: Our study shows that the increase in
      the unenhanced T1 signal intensity has a linear relationship with the eMRIn in
      patients with MS and BM. Indeed, we estimated a linear regression model to fit
      the progressive increase in T1 signal intensity of the dentate nucleus after
      multiple enhanced MRI scans. This finding suggests substantial dechelation of
      gadodiamide in patients with normal renal function, raising further concerns
      regarding the stability of this agent. Further comparative studies with other
      gadolinium chelates, specifically both linear and macrocyclic, are strongly
      recommended.

PMID- 24872010
TI  - USDA snack food and beverage standards: how big of a stretch for the states?
AB  - BACKGROUND: The USDA snack food and beverage standards take effect in school year
      (SY) 2014-2015. Although the USDA standards will provide nationwide requirements,
      concerns exist about compliance. This study examined whether existing state laws
      are aligned with the USDA standards to determine whether some states may be
      better positioned to facilitate compliance. METHODS: Codified state statutory and
      regulatory laws effective for SY 2012-2013 for each of the 50 states and the
      District of Columbia were identified through Boolean keyword searches using the
      Westlaw and LexisNexis databases. Laws were analyzed for alignment with 18 snack
      food and beverage provisions contained within the USDA standards. RESULTS: Thirty
      eight states had snack food and beverage standards; 33 states' laws exceeded
      restrictions on foods of minimal nutritional value. Of the 33 states, no states'
      laws fully met the USDA's standards, 16 states' laws fully met and 10 states'
      laws partially met at least one USDA provision, and seven states' laws met no
      USDA provisions. One state's law met 9 of 18 provisions. On average, states met 4
      of 18 provisions. States were more likely to meet individual USDA beverage than
      snack provisions. CONCLUSIONS: Implementation and compliance with the USDA
      standards may be facilitated in states with laws already containing provisions
      aligned with the USDA standards and may be more difficult in states with fewer or
      no provisions in alignment, suggesting possible geographic areas for the USDA to
      target with technical assistance and training efforts and for advocates to work
      in to facilitate compliance.

PMID- 24872009
TI  - Could moderate alcohol intake be recommended to improve vaccine responses?
AB  - The impact of alcohol consumption on human health is complex and modulated by
      several factors such as patterns and amount of drinking, genetics, the organ
      system studied, as well as the sex and age of the user. There is strong evidence
      that chronic ethanol abuse is associated with increased morbidity and mortality,
      immunosuppression and increased susceptibility to both bacterial and viral
      infections. In contrast, moderate alcohol consumption exerts positive effects
      including decreased mortality, and improved cardiovascular disease and insulin
      sensitivity. Interestingly, accumulating evidence also supports an immune
      boosting effect of moderate alcohol. In this editorial, we summarize the findings
      that support a positive effect of moderate alcohol on host immunity. We also
      discuss the limitations of the previous data and emphasize the importance of
      additional studies to uncover mechanisms for these immune-stimulating effects in
      order to extend these benefits to vulnerable segments of the population who
      cannot consume alcohol. 

PMID- 24872014
TI  - Controlled, reversible, and nondestructive generation of uniaxial extreme strains
      (>10%) in graphene.
AB  - Theoretical calculations have predicted that extreme strains (>10%) in graphene
      would result in novel applications. However, up to now the highest reported
      strain reached ~1.3%. Here, we demonstrate uniaxial strains >10% by pulling
      graphene using a tensile-MEMS. To prevent it from slipping away it was locally
      clamped with epoxy using a femtopipette. The results were analyzed using Raman
      spectroscopy and optical tracking. Furthermore, analysis proved the process to be
      reversible and nondestructive for the graphene.

PMID- 24872011
TI  - Accessibility over availability: associations between the school food environment
      and student fruit and green vegetable consumption.
AB  - BACKGROUND: No national studies have examined associations between (1) school
      food availability and accessibility and (2) secondary student fruit and vegetable
      (FV) consumption. This article uses 5 years of nationally representative data
      from secondary school students to examine associations between the school food
      environment and student fruit and green vegetable consumption. METHODS: From 2008
      to 2012, cross-sectional, nationally representative data from US middle and high
      school students were collected annually on self-reported fruit and green
      vegetable consumption. Each year, data from administrators at each relevant
      school were collected on food item availability (any venue) and accessibility
      (total number of school sources). Data were obtained from 10,254 eighth-grade
      students in 317 schools and 18,898 tenth- and 12th-grade students in 518 schools.
      Associations were estimated by multi-level models controlling for student- and
      school-level characteristics. RESULTS: Availability showed minimal association
      with student consumption. Candy/regular-fat snack accessibility was associated
      negatively with middle school fruit consumption. Salad bar availability and
      accessibility were positively associated with middle school green vegetable
      consumption; FV accessibility was associated positively with high school fruit
      and green vegetable consumption. Significant associations were consistent across
      student racial/ethnic and socioeconomic groups. CONCLUSIONS: Forthcoming USDA
      nutrition standards for school foods and beverages sold outside of reimbursable
      meal programs should result in the removal of school candy/regular-fat snacks. In
      deciding which items to make available under the new standards, schools should
      consider increasing the number of FV sources-including salad bars-thereby
      potentially increasing student FV consumption.

PMID- 24872015
TI  - Association between use of multiple psychoactive medicines and hospitalization
      for falls: retrospective analysis of a large healthcare claim database.
AB  - BACKGROUND: Little is known about the impact of taking multiple psychoactive
      medicines on the risk of hospitalization for falls. OBJECTIVE: To identify the
      association between multiple psychoactive medicine use and hospitalization for
      falls. METHODS: A retrospective cohort study was conducted between July 2011 and
      June 2012 in the Australian veteran population who had been dispensed at least
      one psychoactive medicine within the previous year. Psychoactive medicines with
      sedative properties included antipsychotics, anxiolytics, hypnotics,
      antidepressants, opioids, anti-epileptics, anti-Parkinson medicines and medicines
      for migraine. The associations between falls and the number of psychoactive
      medicines used or the number of doses were analysed in comparison with falls that
      occurred when no psychoactive medicine was used. RESULTS: The adjusted results
      showed a significantly increased risk of falls when patients were on one or more
      psychoactive medicines or were receiving 0.1-0.9 defined daily dose (DDD) or more
      per day. The incident rate ratios (IRRs) were 1.22 (95% confidence interval [CI]
      1.08-1.38) for those on one psychoactive medicine, 1.70 (95% CI 1.45-1.99) for
      those on two, 1.96 (95% CI 1.58-2.43) for those on three or four, and 3.15 (95%
      CI 1.90-5.23) for those on five or more. A similar result was observed when the
      data were analysed by dose, with the highest risk being found for those taking
      three or more DDD per day (adjusted IRR 4.26, 95% CI 2.75-6.58). CONCLUSION:
      Increased numbers or increased doses of psychoactive medicines are associated
      with an increased risk of hospitalization for falls in older adults. Strategies
      to reduce the psychoactive medicine burden are likely to translate into
      significant health benefits.

PMID- 24872016
TI  - Assessment of dentinal tubule invasion capacity of Enterococcus faecalis under
      stress conditions ex vivo.
AB  - AIM: To investigate the dentinal tubule invasion capacity of Enterococcus
      faecalis under alkaline and energy starvation stress conditions. METHODOLOGY: The
      root canals from human single-rooted teeth (n = 40) were infected with E.
      faecalis under alkaline (pH 9, 10, 11 and 12) and energy starvation (no glucose,
      0.05% glucose and 0.15% glucose) stress conditions. The root canals were prepared
      in a standard manner and treated to remove the smear layer before incubation.
      After 4 weeks of cultivation, the roots were split vertically into two halves:
      one half was processed for biofilm formation analysis using a scanning electron
      microscope; the other half was stained with fluorescent DNA-binding reagents,
      washed thoroughly and sectioned (100 MUm thick), and the depth of tubule invasion
      by the microorganism was examined by confocal laser-scanning microscopy. The
      extent of dentine tubule invasion was analysed statistically. RESULTS: The E.
      faecalis strain resulted in biofilm formation and dentine tubules invasion under
      all of the stress conditions, except for pH 11 and 12 conditions. However, the
      tubule penetration distance was markedly reduced in these stress conditions (P <
      0.01) compared with in tryptic soy broth (TSB) or pH 7 medium. The invasion depth
      in the middle root dentine was significantly higher than in the apical sections
      in TSB and energy starvation medium (P < 0.01). CONCLUSIONS: Ex vivo E. faecalis
      formed biofilms and colonized dentine under alkaline and glucose starvation
      stress conditions, but its ability to invade dentine tubules was significantly
      decreased.

PMID- 24872017
TI  - Pump-free multi-well-based microfluidic system for high-throughput analysis of
      size-control relative genes in budding yeast.
AB  - Time-lapse single cell imaging by microscopy can provide precise cell information
      such as the cell size, the cell cycle duration, protein localization and protein
      expression level. Usually, a microfluidic system is needed for these measurements
      in order to provide a constant culture environment and confine the cells so that
      they grow in a monolayer. However, complex connections are required between the
      channels inside the chip and the outside media, and a complex procedure is needed
      for loading of cells, thereby making this type of system unsuitable for
      application in high-throughput single cell scanning experiments. Here we provide
      a novel and easily operated pump-free multi-well-based microfluidic system which
      enables the high-throughput loading of many different budding yeast strains into
      monolayer growth conditions just by use of a multi-channel pipette. Wild type
      budding yeast (Saccharomyces cerevisiae) and 62 different budding yeast size
      control relative gene deletion strains were chosen for scanning. We obtained
      normalized statistical results for the mother cell doubling time, daughter cell
      doubling time, mother cell size and daughter cell size of different gene deletion
      strains relative to the corresponding parameters of the wild type cells.
      Meanwhile, we compared the typical cell morphology of different strains and
      analyzed the relationship between the cell genotype and phenotype. This method
      which can be easily used in a normal biology lab may help researchers who need to
      carry out the high-throughput scanning of cell morphology and growth. 

PMID- 24872018
TI  - Patient perception of wound photography.
AB  - The objectives of this study were to provide an assessment of photographic
      documentation of the wound from the patients' perspective and to evaluate whether
      this could improve patients' understanding of and involvement in their wound
      care. Our results revealed that most patients visiting the wound care clinic have
      difficult-to-see wounds (86%). Only 20% of patients monitor their wounds and
      instead rely on clinic or nurse visits to track the healing progress. There was a
      significant association between patients' ability to see their wound and their
      subsequent memory of the wound's appearance. This was especially true for
      patients who had recently begun visiting the wound care clinic. This relationship
      was not present in patients who had visited the clinic for 3  or more years.
      Patients reported that the inability to see their wounds resulted in feeling a
      loss of autonomy. The majority of patients reported that photographing their
      wounds would help them to track the wound progress (81%) and would afford them
      more involvement in their own care (58%). This study provides a current
      representation of wound photography from the patients' perspective and reveals
      that it can motivate patients to become more involved in the management of their
      wounds - particularly for patients with difficult-to-see wounds. 

PMID- 24872019
TI  - MaTrace: tracing the fate of materials over time and across products in open-loop
      recycling.
AB  - Even for metals, open-loop recycling is more common than closed-loop recycling
      due, among other factors, to the degradation of quality in the end-of-life (EoL)
      phase. Open-loop recycling is subject to loss of functionality of original
      materials, dissipation in forms that are difficult to recover, and recovered
      metals might need dilution with primary metals to meet quality requirements.
      Sustainable management of metal resources calls for the minimization of these
      losses. Imperative to this is quantitative tracking of the fate of materials
      across different stages, products, and losses. A new input-output analysis (IO)
      based model of dynamic material flow analysis (MFA) is presented that can trace
      the fate of materials over time and across products in open-loop recycling taking
      explicit consideration of losses and the quality of scrap into account.
      Application to car steel recovered from EoL vehicles (ELV) showed that after 50
      years around 80% of the steel is used in products, mostly buildings and civil
      engineering (infrastructure), with the rest mostly resided in unrecovered
      obsolete infrastructure and refinery losses. Sensitivity analysis was conducted
      to evaluate the effects of changes in product lifespan, and the quality of scrap.

PMID- 24872020
TI  - Multi-functional MBIT for peptide tandem mass spectrometry.
AB  - Isobaric tags have been widely used for the identification and quantification of
      proteins in mass spectrometry-based proteomics. The mass-balanced, (1) H/(2) H
      isotope-coded dipeptide tag (MBIT) is a multifunctional isobaric tag based on N
      acetyl-Ala-Ala dipeptide containing an amine-reactive linker that conjugates the
      tag to the primary amines of proteolytic peptides. MBITs provide a pair of
      isotope-coded quantitation signals separated by 3 Da, which enables 2-plex
      quantification and identification of proteins in the 15-250 fmol range. Various
      MBITs diversified at the N-acetyl group or at the side chain of the first alanine
      provide a pair of bs ions as low-mass quantitation signals in a distinct mass
      window. Thus, a combination of different MBITs allows multiplex quantification of
      proteins in a single liquid chromatography-mass spectrometry experiment. Unlike
      other isobaric tags, MBITs also offer a pair of ys ions as high-mass quantitation
      signals in a noise-free region, facilitating protein quantification in quadrupole
      ion trap mass spectrometers. Uniquely, bS ions, forming N-protonated oxazolone,
      undergo unimolecular dissociation and generate the secondary low-mass
      quantitation signals, aS ions. The yield of aS ions derived from bS ions can be
      used to measure the temperature of bS ions, which enables a reproducible
      acquisition of the peptide tandem mass spectra. Thus, MBITs enable multiplexed
      quantitation of proteins and the concurrent measurement of ion temperature using
      bS and aS signal ions as well as the isobaric protein quantitation in resonance
      type ion trap using yS (complement of bS ) signal ions. This review provides an
      overview of MBITs with a focus on the multi-functionality that has been
      successfully demonstrated in the peptide tandem mass spectrometry.

PMID- 24872021
TI  - SPACA3 gene variants in a New Zealand cohort of infertile and fertile couples.
AB  - SPRASA (also referred to as SLLP1) is a protein identified in the acrosome of
      human sperm and encoded by the gene SPACA3. SPRASA is associated with sperm
      oocyte recognition and binding, and may play a role in fertility. In order to
      determine whether variants in the SPACA3 gene are associated with human
      infertility, we undertook a genetic analysis of 102 infertile and 104 fertile
      couples. Three gene variants were identified using PCR-based DNA sequencing; 1)
      an insertion of TGC within a quadruple tri-nucleotide (TGC) repeat region in the
      5' untranslated region (UTR) (g.-22TGC(4_5), 2) a guanine to adenosine transition
      at position 239 (c.239G>A) resulting in a non-synonymous amino acid substitution
      from cysteine to tyrosine (p.C80Y) at position 80 in the putative transmembrane
      region, and 3) a novel nucleotide variant (c.691G>C) located in the 3'UTR. A
      functional effect of the g.-22TGC (4_5) was confirmed by a luciferase expression
      assay, while the effects of the variants c.239G>A and c.691G>C were predicted
      using in silico analysis. Although the frequencies of these variants were not
      significantly different between the infertile and fertile populations, we present
      evidence that the variants could affect the expression levels or function of
      SPRASA, thereby affecting a couple's fertility. Larger populations, especially
      individuals/couples with unexplained infertility, need to be screened for these
      variants to validate a relationship with fertility.

PMID- 24872023
TI  - Spontaneous eyeblink activity under different conditions of gaze (eye position)
      and visual glare.
AB  - PURPOSE: To further evaluate the spontaneous eyeblink rate (SEBR) of healthy
      adult human subjects according to direction of gaze, especially in the presence
      of bright light reflective glare. METHODS: On 32 subjects aged between 18 and 24
      years, separate video recordings of 5 min duration were made with different
      conditions of gaze (horizontal, slightly upwards or slightly downwards) under
      normal lighting or a distant lighting glare source. RESULTS: The SEBR in primary
      eye gaze under normal lighting was 11.7 +/- 0.9 eyeblinks/min with a coefficient
      of variation (COV) of 20.5 %. A non-significant decrease in SEBR was noted with
      downward gaze, but a slight significant increase with upward gaze in both SEBR
      (to 13.0 +/- 1.1 eyeblinks/min) and COV (average 26.1 %). In the presence of
      glare, SEBR in primary eye gaze increased significantly (p < 0.001) to 14.4 +/-
      1.3 eyeblinks/min, with an obvious time-related progressive increase (p < 0.001).
      On upward gaze in the presence of a glare stimulus, SEBR progressively increased
      even further (average 15.0 +/- 2.4 eyeblinks/min; p < 0.001), as did the COV (to
      29.2 %). CONCLUSIONS: The results indicate that spontaneous eyeblink activity in
      silence can be affected by the presence of a glare light source, especially if
      the subjects are looking slightly upwards. This scenario should be avoided, if at
      all possible, in assessments of spontaneous eyeblink activity.

PMID- 24872024
TI  - Investigation of summation mechanisms in the pupillomotor system.
AB  - BACKGROUND: To ascertain whether the pupillary response amplitude shows spatial
      summation of responses with increasing size of retinal stimulation, and to
      examine the pupillary responses for evidence of surround inhibition, analogous to
      that found in the receptive fields of the retinal ganglion cells. METHODS: By
      means of infrared-video-pupillography, the pupil reaction to stimuli of
      increasing size (1-15 degrees ) was measured in 30 normal subjects. Four
      different retinal locations (0 degrees , 20 degrees  and 40 degrees  eccentricity
      on the upper temporal retina and 20 degrees  eccentricity on the lower nasal
      retina) were examined at four different stimulus luminances (17, 47, 87 and 140
      cd/m(2)). RESULTS: When the average log amplitude of the pupil light reaction
      from the 30 subjects is plotted as a function of the log area of the stimulus, a
      bi-linear response is observed, which is most pronounced for the two higher
      luminances. The intersection points of the two linear responses are 2.01 degrees 
      in the fovea, 2.80 degrees  at 20 degrees  upper temporal retina, 2.85 degrees 
      at 20 degrees  lower nasal retina and 4.86 degrees  at 40 degrees  upper temporal
      retina. CONCLUSIONS: This study suggests that pupillomotor summation areas
      consist of both summation and inhibitory zones. They show larger diameters than
      receptive fields of retinal ganglion cells and do not appear to reflect pupillary
      summation areas of the pretectal olivary nucleus luminance neurons.

PMID- 24872025
TI  - Episomal expression of truncated listeriolysin O in LmddA-LLO-E7 vaccine enhances
      antitumor efficacy by preferentially inducing expansions of CD4+FoxP3- and CD8+ T
      cells.
AB  - Studies have shown that Listeria monocytogenes (Lm)-based vaccine expressing a
      fusion protein comprising truncated listeriolysin O (LLO) and human papilloma
      virus (HPV) E7 protein (Lm-LLO-E7) induces a decrease in regulatory T cells
      (Treg) and complete regression of established, transplanted HPV-TC-1 tumors in
      mice. However, how the Lm-based vaccine causes a decrease in Tregs remains
      unclear. Using a highly attenuated Lm dal dat DeltaactA strain (LmddA)-based
      vaccine, we report here that the vector LmddA was sufficient to induce a decrease
      in the proportion of Tregs by preferentially expanding CD4(+)FoxP3(-) T cells and
      CD8(+) T cells by a mechanism dependent on and directly mediated by LLO. Episomal
      expression of a nonhemolytic truncated LLO in Lm (LmddA-LLO) significantly
      augmented the expansion, thus further decreasing Treg frequency. Although
      adoptive transfer of Tregs compromised the antitumor efficacy of the LmddA-LLO-E7
      vaccine, a combination of LmddA-LLO and an Lm-based vaccine expressing E7 protein
      (Lm-E7) induced complete regression against established TC-1 tumors. An
      engineered LLO-minus Lm expressing perfringolysin O (PFO) that enables the
      recombinant bacteria to exit from the phagolysosome without LLO confirmed that
      the adjuvant effect was dependent on LLO. These results suggest that LLO may
      serve as a promising adjuvant by preferentially inducing the expansions of
      CD4(+)FoxP3(-) T cells and CD8(+) T cells, thus reducing the ratio of Tregs to
      CD4(+)FoxP3(-) T cells and to CD8(+) T cells favoring immune responses to
      eradicate tumor.

PMID- 24872026
TI  - In vitro characterization of the anti-PD-1 antibody nivolumab, BMS-936558, and in
      vivo toxicology in non-human primates.
AB  - The programmed death-1 (PD-1) receptor serves as an immunologic checkpoint,
      limiting bystander tissue damage and preventing the development of autoimmunity
      during inflammatory responses. PD-1 is expressed by activated T cells and
      downmodulates T-cell effector functions upon binding to its ligands, PD-L1 and PD
      L2, on antigen-presenting cells. In patients with cancer, the expression of PD-1
      on tumor-infiltrating lymphocytes and its interaction with the ligands on tumor
      and immune cells in the tumor microenvironment undermine antitumor immunity and
      support its rationale for PD-1 blockade in cancer immunotherapy. This report
      details the development and characterization of nivolumab, a fully human IgG4
      (S228P) anti-PD-1 receptor-blocking monoclonal antibody. Nivolumab binds to PD-1
      with high affinity and specificity, and effectively inhibits the interaction
      between PD-1 and its ligands. In vitro assays demonstrated the ability of
      nivolumab to potently enhance T-cell responses and cytokine production in the
      mixed lymphocyte reaction and superantigen or cytomegalovirus stimulation assays.
      No in vitro antibody-dependent cell-mediated or complement-dependent cytotoxicity
      was observed with the use of nivolumab and activated T cells as targets.
      Nivolumab treatment did not induce adverse immune-related events when given to
      cynomolgus macaques at high concentrations, independent of circulating anti
      nivolumab antibodies where observed. These data provide a comprehensive
      preclinical characterization of nivolumab, for which antitumor activity and
      safety have been demonstrated in human clinical trials in various solid tumors.

PMID- 24872027
TI  - Combination rapid-acting nicotine mouth spray and nicotine patch therapy in
      smoking cessation.
AB  - INTRODUCTION: Improved smoking cessation rates are urgently required if New
      Zealand is to reach its target of a smokefree nation by 2025, during which some
      600,000 smokers will need to quit. Nicotine replacement therapy remains a core
      part of the pharmacological approach to smoking cessation. Oral nicotine
      solutions with rapid onset have recently become available. We have examined the
      effect of a nicotine spray and a nicotine patch on smoking cessation for 12
      months. METHODS: We enrolled potential participants-smokers wanting to quit aged
      18-70 years, who smoked >=9 cigarettes per day-with Fagerstrom Test of Nicotine
      Dependence score >=3 in a double-blind trial in 3 trial sites. Smokers were
      randomized to a nicotine or placebo spray for 6 months, and all received nicotine
      patches daily for 5 months. They were followed at regular intervals for 12
      months. RESULTS: A total of 1,423 subjects were randomized to nicotine oral spray
      (1mg of nicotine free base per spray) plus nicotine patch or a placebo spray and
      nicotine patch. The nicotine mouth spray plus nicotine patch showed significant
      improvements in prolonged abstinence for all measures to 6 months (7 consecutive
      days at each visit for 6 months: 15.5% vs. 10.6%; p = .006) for the combination
      versus placebo and nicotine patch. Thereafter, the differences were not
      significant. CONCLUSIONS: The addition of a nicotine mouth spray to a nicotine
      replacement patch in a population of smokers receiving a low level of behavioral
      support improved early quitting, but the effects were not sustained.

PMID- 24872028
TI  - Informal Peer Interaction and Practice Type as Predictors of Physician
      Performance on Maintenance of Certification Examinations.
AB  - IMPORTANCE: Physicians can demonstrate mastery of the knowledge that supports
      continued clinical competence by passing a maintenance of certification
      examination (MOCEX). Performance depends on professional learning and
      development, which may be enhanced by informal routine interactions with
      colleagues. Some physicians, such as those in solo practice, may have less
      opportunity for peer interaction, thus negatively influencing their examination
      performance. OBJECTIVE: To determine the relationship among level of peer
      interaction, group and solo practice, and MOCEX performance. DESIGN, SETTING, AND
      PARTICIPANTS: Longitudinal cohort study of 568 surgeons taking the 2008 MOCEX.
      Survey responses reporting the level of physicians' peer interactions and their
      practice type were related to MOCEX scores, controlling for initial qualifying
      examination scores, practice type, and personal characteristics. EXPOSURES: Solo
      practice and amount of peer interaction. MAIN OUTCOMES AND MEASURES: Scores on
      the MOCEX and pass-fail status. RESULTS: Of the 568 surgeons in the study sample,
      557 (98.1%) passed the examination. Higher levels of peer interaction were
      associated with a higher score (beta = 0.91 [95% CI, 0.31-1.52]) and higher
      likelihood of passing the examination (odds ratio, 2.58 [1.08-6.16]). Physicians
      in solo (vs group) practice had fewer peer interactions (beta = -0.49 [95% CI, 
      0.64 to -0.33), received lower scores (beta = -1.82 [-2.94 to -0.82]), and were
      less likely to pass the examination (odds ratio, 0.22 [0.06-0.77]). Level of peer
      interaction moderated the relationship between solo practice and MOCEX score;
      solo practitioners with high levels of peer interaction achieved an MOCEX
      performance on a par with that of group practitioners. CONCLUSIONS AND RELEVANCE:
      Physicians in solo practice had poorer MOCEX performance. However, solo
      practitioners who reported high levels of peer interaction performed as well as
      those in group practice. Peer interaction is important for professional learning
      and quality of care.

PMID- 24872030
TI  - The genus Paravelia Breddin, 1898 (Hemiptera: Heteroptera: Veliidae) in Brazil,
      with descriptions of eight new species.
AB  - Eight new species of Paravelia Breddin, 1898 from Brazil are described and
      illustrated: P. amapaensis sp. nov. from Amapa State, P. bipunctata sp. nov. from
      Minas Gerais, Mato Grosso and Mato Grosso do Sul States, P. bilobata sp. nov. and
      P. polhemusi sp. nov. from Mato Grosso State, P. bahiana sp. nov. from Bahia
      State, P. lacrymosa sp. nov. from Minas Gerais State, P. micromaculata sp. nov.
      from Maranhao State, and P. ornata sp. nov. from Amazonas State. The genus is
      redescribed, with photos of the dorsal view for nineteen species: P. basalis
      (Spinola), P. biae Spangler, P. boliviana Breddin, P. bullialata Polhemus &
      Polhemus, P. capillata (Drake& Harris), P. capixaba Moreira, Nessimian & Rudio,
      P. conata (Hungerford), P. dilatata Polhemus & Polhemus, P. foveata Polhemus &
      Polhemus, P. itatiayana (Drake), P. lanemeloi Moreira & Barbosa, P. manausana
      Polhemus & Polhemus, P. nieseri Moreira & Barbosa, P. platensis (Berg), P. recens
      (Drake & Harris), P. rotundanotata (Hungerford), P. spinifera Polhemus &
      Polhemus, P. splendoris (Drake & Harris) and P. williamsi (Hungerford). Three of
      these species are recorded for the first time from Brazil: P. platensis, P.
      spinifera and P. williamsi. Also, the macropterous forms of P. capixaba and P.
      dilatata are described. Lastly, an identification key to the 36 species of
      Paravelia recorded from Brazil and a checklist of described species are
      presented. 

PMID- 24872029
TI  - Natural cotton fibers as adsorbent for solid-phase extraction of polycyclic
      aromatic hydrocarbons in water samples.
AB  - A natural material, cotton fiber, has been applied as a solid-phase extraction
      (SPE) adsorbent for sample preparation for the analysis of polycyclic aromatic
      hydrocarbons (PAH) in water samples using high-performance liquid chromatography.
      The cotton fiber was used directly without any chemical modifications, which
      avoided a complex synthesis process and consumption of a large volume of organic
      solvent. The conditions affecting the extraction efficiency were optimized to
      achieve high detection sensitivity, and included elution solvent, ultrasonic
      elution time, extraction time, sample volume, salt concentration and organic
      modifier addition. Under the optimal conditions, the detection limits for seven
      PAH compounds could reach up to 0.1-2.0 ng L(-1). The method accuracy was
      evaluated using recovery measurements in standard spiked samples and good
      recoveries of 70.69-110.04% with relative standard deviations of less than 10%
      have been achieved. Consequently, the method developed was successfully applied
      for determining PAH in environmental samples: snow water, metal-fabrication
      factory wastewater and Xiangjiang River water, with PAH contents ranging from
      13.2 to 83.1 ng L(-1). Therefore, using cotton fiber as a new SPE adsorbent, was
      easy to prepare, had a low cost and great reusability, and this implies it is a
      promising method for sample preparation. 

PMID- 24872032
TI  - Demystifying three species of Ctenidae (Arachnida: Araneae) described by Embrik
      Strand. Part I, Ecuador.

PMID- 24872031
TI  - DNA barcoding of Vietnamese bent-toed geckos (Squamata: Gekkonidae:
      Cyrtodactylus) and the description of a new species.
AB  - Species of bent-toed gecko (Cyrtodactylus) in Vietnam have been described at a
      rate of nearly four species per year since 2007 mostly based on morphological
      data. A tool that guides species delimitation will accelerate the rate of
      documentation, and at a time when the recognition of species greatly benefits
      conservation. We use DNA barcoding using COI (550 bp) to re-examine the levels of
      genetic divergence and taxonomic status of 21 described species of Vietnamese
      bent-toed geckos. Tree-based analyses resolve all sampled species and identify
      potential undescribed taxa. Kimura 2-parameter genetic distances between the
      described species average 21.0+/-4.2% and range from 4.3% to 28.7%. Further, our
      analyses discover two potentially new species from Vietnam, two from Laos and one
      from China. Herein we describe the new species Cyrtodactylus puhuensis sp. nov.
      from Vietnam on the basis of both genetics and morphology. Genetically, it
      differs from the remaining species by an average K2P distance of 24.0+/-1.8%.
      Morphologically, the new species is diagnosed by its medium-size (snout-vent
      length 79.24 mm and tail length 82.59 mm, for the single known individual), in
      having a series of moderately enlarged transverse subcaudals and a series of
      moderately enlarged femoral scales that extend from precloacal scales, in
      possessing femoral scales without pores, with males having five precloacal pores,
      and in exhibiting 8 supralabials, 10 infralabials, 23 narrow subdigital lamellae
      on its fourth toe, and 36 transverse ventrals. 

PMID- 24872033
TI  - Telosticta iban sp. nov. from Sarawak (Odonata: Zygoptera: Platystictidae) .
AB  - T. iban sp. nov. is described from the Lanjak Entimau Wildlife Sanctuary in
      Sarawak, Malaysian Borneo. Both sexes can be distinguished from all other species
      of Telosticta by the form of the antehumeral markings. 

PMID- 24872034
TI  - The advertisement call and geographic distribution of Odontophrynus lavillai Cei,
      1985 (Anura: Odontophrynidae).

PMID- 24872035
TI  - Lauriana Ren & Qin, a new genus of the tribe Tropidocephalini (Hemiptera:
      Fulgoromorpha: Delphacidae) from China.
AB  - A new delphacid genus and species, Lauriana senticosa Ren & Qin, gen. et sp. nov.
      (Hemiptera: Delphacidae: Tropidocephalini) is described from Sichuan, China.
      Habitus photos and illustrations of male genitalia of the new species are given,
      and the differences between the new genus and its closely related genera are
      discussed. 

PMID- 24872036
TI  - Two new turrid species (Gastropoda: Pseudomelatomidae) from the Palawan region,
      the Philippines.
AB  - Species richness of tropical marine molluscs is considerably underestimated
      (Bouchet et al. 2002). Indeed, the molluscan faunas of some regions, such as
      Palawan in the western Pacific, have received little attention and some hyper
      diverse groups, such as the turrids (a parapyhletic group of Conoidea, formerly
      known as Turridae), are barely documented. For example, apart from original
      descriptions of two turrid taxa that have their type locations in Palawan
      (Comitas aequatorialis palawanica Powell, 1969 and Mangilia quadrasi Boettger,
      1895 = Gingicithara notabilis (E. A. Smith, 1888)), there are no published
      records of turrids from this region. We have been fortunate to have access to
      recent collections of turrids from different parts of Palawan. Examination of
      these materials has revealed existence of several undescribed and potentially
      endemic species. In the present paper two new Pseudomelatomidae species are
      described. 

PMID- 24872037
TI  - The advertisement call of Haddadus aramunha (Cassimiro, Verdade & Rodrigues,
      2008) (Anura, Craugastoridae).

PMID- 24872038
TI  - Advertisement call of Rhinella crucifer (Wied-Neuwied, 1821) (Anura: Bufonidae)
      from southern Bahia, Brazil.

PMID- 24872039
TI  - A reply to Pall-Gergely's suggestions to improve the taxonomy index (T-Index)
      introduced by Valdecasas (2011) .

PMID- 24872040
TI  - New species of Hebefustis Siebenaller & Hessler 1977 (Isopoda, Asellota,
      Nannoniscidae) from the Clarion Clipperton Fracture Zone (equatorial NE Pacific).
AB  - Macrofaunal collections obtained during the French-German BIONOD expedition to
      the Clarion Clipperton Fracture Zone (CCFZ), equatorial NE Pacific, in spring
      2012 yielded two new nannoniscid species, Hebefustis juansenii sp. n. and H.
      vecino sp. n., which are described in the current paper. The number and position
      of posterolateral spines of the pleotelson distinguishes the two new species from
      all other species in the genus. Both species are similar to each other differ,
      though, in the length of maxilliped epipodite, the presence of a robust spine on
      pereonite 2 (in H. juansenii sp. n.) as well as the shape of pereonite 4 anterior
      margin. They also resemble H. primitivus Menzies, 1962 but can be differentiated
      from the latter by the shape of lateral margins of pereonites 1-4 and the
      setation and shape of male pleopod 1. A distribution map and a taxonomic key to
      all known species in the genus are provided, as well as a checklist of known
      nannoniscid species from the Pacific is presented. 

PMID- 24872041
TI  - Endecous apterus: a new species of cave cricket from northeast Brazil, with
      comments on the use of subterranean habitats by Luzarinae crickets (Orthoptera:
      Grylloidea: Phalangopsidae: Luzarinae).
AB  - In this study we describe the first apterous species of Endecous Saussure (1878),
      collected in two caves at Ituacu, Bahia State, Brazil. In Brazil, Endecous is the
      most widespread cricket in hypogean environments and its species can colonize
      caves and inhabit the entrance and the aphotic zones; Endecous species can also
      be found in the litter, rock gullies, crevices, burrows, and any natural
      cavities. The use of subterranean habitat by Endecous crickets and its related
      genera are discussed. 

PMID- 24872042
TI  - Contributions to the Opiinae (Hymenoptera: Braconidae) of Eastern Iran with
      updated checklist of Iranian species.
AB  - The present work collects the checklist of species of Opiinae (Hymenoptera:
      Braconidae) from Iran and presents new information about the specimens captured
      in the Sistan and Baluchestan province during 2009-2011. A total of 68 species
      belonging to eight genera have been listed, of which nine species including Opius
      (Hypocynodus) arundinis Fischer, 1964a; Opius (Hypocynodus) bouceki (Fischer,
      1958b); Opius (Opius) caricivorae Fischer, 1964b; Opius (Opius) exilis Haliday,
      1837; Opius (Opiothorax) opacus Fischer, 1968; Opius (Allophlebus) tabificus
      Papp, 1979; Phaedrotoma biroica (Fischer et Beyarslan 2005a); Phaedrotoma
      mirabunda (Papp, 1982) and Xynobius rudis (Wesmaelm, 1835) are new records from
      Iran. 

PMID- 24872043
TI  - Two new species of Esthemopsis C. Felder & R. Felder, 1865 (Lepidoptera:
      Riodinidae: Symmachiini) from southeastern and northeastern Brazil, with
      taxonomic comments on Esthemopsis teras (Stichel, 1910) stat. rev. and
      Esthemopsis pallida Lathy, 1932 stat. nov.
AB  - Two new species of Esthemopsis C. Felder & R. Felder, 1865 from southeastern and
      northeastern Brazil are described, Esthemopsis sateri sp. nov. and Esthemopsis
      diamantina sp. nov., and revised and new combinations are proposed for
      Esthemopsis teras (Stichel, 1910) stat. rev. and Esthemopsis pallida Lathy, 1932
      stat. nov., respectively. Lectotypes are designated for Lepricornis teras
      Stichel, 1910 and Esthemopsis caerulea pallida Lathy, 1932. The habitus of male
      and female specimens of the species discussed are illustrated; male head and
      labial palpus pictures, male and female genitalia illustrations are provided. 

PMID- 24872044
TI  - Two new species of Neotyphloceras (Siphonaptera: Ctenophthalmidae) from
      Argentinean Patagonia.
AB  - Two new species of Neotyphloceras Rothschild, parasites of sigmodontine rodents
      from Argentinean Patagonia, are described and illustrated: N. crackensis n. sp.
      and N. pardinasi n. sp. These species are compared with their morphologically
      closest relatives. Males are characterized by the shape of the upper lobe of the
      fixed process of clasper; the shape and chaetotaxy of the distal arm of sternum
      IX and by the shape of the crochet of the aedeagus; females by the contour of the
      distal margin of sternum VII. Neotyphloceras pardinasi n. sp. is reported from
      western Chubut Province, while N. crackensis n. sp. is known from the eastern
      regions of Chubut and Santa Cruz Provinces. With these reports, the geographical
      distribution of Neotyphloceras is extended to eastern Patagonia. A key to the
      species and subspecies of Neotyphloceras is provided. 

PMID- 24872045
TI  - A new species of the pontoniine shrimp genus Eupontonia (Crustacea: Decapoda:
      Caridea: Palaemonidae) from the Ryukyu Islands, Japan.
AB  - A third species of the pontoniine shrimp genus Eupontonia Bruce, 1971, E.
      gracilipes n. sp., is described and illustrated on the basis of a single female
      specimen collected from shallow water of Ishigaki Island, southern Ryukyu
      Islands, Japan. The new species is readily distinguished from the two congeneric
      species, E. noctalbata Bruce, 1971 and E. oahu Bruce, 2010, by a number of
      morphological characters, including the presence of a distinct postrostral median
      ridge and of the postrostral median tooth on the carapace. It is considered to be
      a free-living species. The generic diagnosis of Eupontonia is slightly emended to
      accommodate the present new species. A key in aid of identification of species of
      Eupontonia is provided. 

PMID- 24872046
TI  - Notes on the Neotropical Zethus Fabricius, 1804 (Hymenoptera, Vespidae,
      Eumeninae) with the description of two new species from Brazil.
AB  - Two new species, Zethus (Zethus) aliceae Lopes, sp. nov. (Brazil) and Z. (Zethus)
      sinuostylus Lopes, sp. nov. (Brazil) are described and figured. New synonymy is
      proposed for Zethus (Zethoides) biglumis Spinola, 1841 (=Zethus ferrugineus de
      Saussure, 1852, syn. nov. 

PMID- 24872047
TI  - A new Stygarctus (Arthrotardigrada: Stygarctidae) from Japan, with entangled
      seminal receptacle ducts.
AB  - Stygarctus ayatori sp. nov. (Arthrotardigrada: Stygarctidae), is described from a
      sandy beach located at Okinoshima, Tateyama Bay, Boso Peninsula, Honshu, Japan.
      The most prominent characters were observed in the female genital structure, with
      the seminal receptacle ducts forming a three-dimensional entanglement near the
      exterior opening, and internal thickening situated peripheral to the gonopore and
      between the gonopore and anus. The new species is distinguished from the
      congeners by these characters; excluding S. abornatus McKirdy et al., 1976 for
      which there is no information on the genital structure. However, S. ayatori sp.
      nov. and S. abornatus can be differentiated by the presence of dorsal spines on
      the former species, which are absent from the latter. 

PMID- 24872048
TI  - A new species of Neobelocera Ding & Yang (Hemiptera: Delphacidae: Delphacinae:
      Tropidocephalini) from China, with a key to species of the genus.
AB  - Neobelocera medogensis sp. nov. (Hemiptera: Delphacidae: Delphacinae:
      Tropidocephalini) is described and illustrated from Medog, Tibet, China. The new
      species can be easily separated from other known species in the genus Neobelocera
      by the color of tegmina and the form of the male genitalia. A key for separation
      of all known species of Neobelocera is also provided. 

PMID- 24872050
TI  - A checklist of the barnacles (Crustacea: Cirripedia: Thoracica) of the Persian
      Gulf and Gulf of Oman with nine new records.
AB  - The present annotated checklist contains 43 species of thoracican barnacles known
      to date from the area, 33 and 26 from the Persian Gulf and the Gulf of Oman,
      respectively. Nine species are new records for the area including Amphibalunus
      subalbidus (Henry, 1973), Armatobalanus allium (Darwin, 1854), Chelonibia patula
      (Ranzani, 1818), Conchoderma hunteri (Owen, 1830), Lepas anserifera Linnaeus,
      1767, Lithotrya valentiana Reinhardt, 1850, Megabalanus coccopoma (Darwin, 1854),
      Megabalanus occator (Darwin, 1854) and Platylepas hexastylos (Fabricius, 1798),
      of which A. subalbidus and M. coccopoma are reported as alien species from the
      region. 

PMID- 24872051
TI  - Nomenclatural corrections, neotype designation and new subspecies description in
      the genus Suiriri (Aves: Passeriformes: Tyrannidae).
AB  - Zimmer et al. (2001) documented two morphological and vocal forms within what was
      then known as Suiriri suiriri affinis, and described the short-billed form as
      Suiriri islerorum. However, studies of the Burmeister type material held at the
      Natural History Collections of the Martin-Luther-University Halle-Wittenberg,
      Germany, revealed the types of Suiriri s. affinis (Burmeister, 1856) to be the
      same taxon as Suiriri islerorum, which name therefore becomes a junior synonym.
      No published name is available for the long-billed form. A new name is therefore
      introduced by an original description in accordance with the International code
      on zoological nomenclature. The original type material of S. s. bahiae
      (Berlepsch, 1893) is confirmed to be lost; a neotype is designated. 

PMID- 24872052
TI  - Revision of the genus Ophioteichus H.L. Clark, 1938 (Ophiuroidea:
      Ophiolepididae).
AB  - In this study we re-describe the ophiuroid genus Ophioteichus H.L. Clark, 1938
      and diagnose the species using existing and new characters found by examining the
      type material. The species Ophiolepis utinomii Irimura, 1967, is very similar to
      the holotype of Ophioteichus multispinum, and is herein transferred to the genus
      Ophioteichus; this transfer expands the geographic range of the genus.
      Ophioteichus is currently composed of three species: Ophioteichus parvispinum,
      Ophioteichus multispinum and Ophioteichus utinomii comb. nov. The genus is now
      known from the eastern part of Australia, Philippines and the coast of Japan,
      with a bathymetric range from littoral down to 45.3 m. 

PMID- 24872053
TI  - A new species of Tongorchestia from Bora Bora in the leeward Society Islands
      (Crustacea, Amphipoda, Talitridae) .
AB  - The new species Tongorchestia borabora sp. nov. is described from Vaitape in Bora
      Bora, Leeward Islands, Society Islands. This is the first talitrid amphipod
      reported from Bora Bora and the third species of Tongorchestia from the Western
      Pacific oceanic islands. Currently Tongorchestia is endemic to oceanic islands in
      the Western Pacific. 

PMID- 24872054
TI  - A new species of Anacanthoroides and redescription of Apedunculata discoidea
      (Monogenoidea) parasitizing Prochilodus argenteus (Actinopterygii) from the Sao
      Francisco River, Brazil.
AB  - Anacanthoroides sanctifrancisci n. sp. from the gills of 'curimata-pacu',
      Prochilodus argenteus from the Sao Francisco River, Brazil, is described and
      illustrated. Anacanthoroides, monotypic, is represented by Anacanthoroides
      mizellei. The new species can be distinguished from A. mizellei by the presence
      of a pair of muscular pseudosuckers in the anterior region of the body, an
      accessory piece not articulated to the male copulatory organ and the number of
      rings in the male copulaty complex. Apedunculata discoidea is redescribed and
      recorded in the gills of P. argenteus. The generic diagnosis of Apedunculata is
      amended. Both genera are recorded for the first time in the Sao Francisco River
      basin. 

PMID- 24872055
TI  - A new species of Duvalius from world's deepest cave (Coleoptera: Carabidae).
AB  - The new hypogean ground beetle, Duvalius abyssimus n. sp., from Krubera-Voronja,
      world's deepest cave (Arabika massif, Western Caucasus) is described and
      illustrated. Diagnostic morphological characters of the imago, male and female
      genitalia are provided. Its relations with other Duvalius Delarouzee species from
      the Western Caucasus geographic area are discussed. An updated overview of the
      biocoenosis of its peculiar habitat is made. 

PMID- 24872056
TI  - Ruthmuelleria, a new genus of Carinodulini (Coleoptera: Coccinellidae:
      Microweiseinae) from South Africa.
AB  - A new genus of ladybird beetles, Ruthmuelleria, belonging to the pantropical
      tribe Carinodulini, is described based on a new species R. grootdrifensis from
      South Africa. The genus is diagnosed by the unique 8-segmented antennae and
      posteriorly-directed metaventral postcoxal lines. A key to the genera and
      discussion of diagnostic characters of Carinodulini are also included. 

PMID- 24872057
TI  - New Indo-Pacific species of Dasyrhicnoessa Hendel, 1934 and Pseudorhicnoessa
      Malloch, 1914 (Diptera: Canacidae: Tethininae).
AB  - Three new species of Dasyrhicnoessa Hendel, 1934 and one of Pseudorhicnoessa
      Malloch, 1914 from the Indo-Pacific area are described and the male terminalia
      illustrated. Among these new species, Dasyrhicnoessa paradoxa sp. nov. and
      Pseudorhicnoessa longicerca sp. nov. are especially noteworthy for the
      morphological peculiarities of the male terminalia. 

PMID- 24872058
TI  - The advertisement call of Dendropsophus pseudomeridianus (Cruz, Caramaschi &
      Dias) (Anura: Hylidae).

PMID- 24872060
TI  - A revision of the lysianassid genus Waldeckia with the description of four new
      species (Crustacea, Amphipoda, Lysianassidae, Waldeckiinae subfam. nov.).
AB  - Waldeckia Chevreux is a genus of scavenging lysianassoid amphipods with
      distribution records from Antarctica, Australia, Thailand, Indonesia, Singapore,
      the Philippines, Vietnam, China and Japan. The genus is revised and diagnosed
      against all other genera of the Lysianassidae and the subfamily Waldeckiinae is
      established. All known species are redescribed and a key is provided. Three new
      species of Waldeckia (W. dempseyae sp. nov., W. tangaroa sp. nov., W. warreen sp.
      nov.) are described from Australian waters, and one (W. selayarensis sp. nov.)
      from Indonesia and Australia. Waldeckia crenulata Pirlot, 1936, from the
      Philippines and Indonesia, is described in detail for the first time. Waldeckia
      chevreuxi Stebbing, 1910 is placed in the synonymy of W. nitens, and W. elephas
      is placed in the synonymy of W. nudum. Orchomene orchospina Hirayama, 1986 and O.
      tomiokaensis Hirayama, 1986 are transferred to Waldeckia. Waldeckia scrupulosa
      Mateus & Mateus, 1986 cannot be placed in a genus based on the original
      description. This revision brings the number of species in the genus to 14. 

PMID- 24872059
TI  - First record of the leafhopper genus Soractellus Evans, 1966 (Hemiptera:
      Cicadellidae: Deltocephalinae) from China, with description of a new species.
AB  - The genus Soractellus Evans, 1966 is reported for the first time based on a new
      species, Soractellus jianfengensis sp. nov., here described and illustrated from
      China. A key is given to distinguish all species of the genus. The type specimens
      of the new species are deposited in the Institute of Entomology, Guizhou
      University, Guiyang, China (GUGC). 

PMID- 24872061
TI  - The Odonata (Insecta) of Patagonia: a synopsis of their current status with
      illustrated keys for their identification.
AB  - Patagonia is a vast landmass with a distinctive environmental and biotic
      heterogeneity. Its Odonata biodiversity is the best known of South America, and
      it is composed of 36 species, of which more than 50% are endemic. We summarize
      the main taxonomic, distributional and biological information including
      illustrated keys for adults and known larvae, and distributional maps. 

PMID- 24872062
TI  - Aracia sinaloae sp. n., a new brooding, simultaneous hermaphroditic fan worm from
      southern Gulf of California (Polychaeta: Sabellidae).
AB  - Currently, only two species are known in the sabellid genus Aracia: A. riwo
      (Rouse, 1996) and A. heterobranchiata (Nogueira, Lopez & Rossi, 2004). The first
      was described from the surface of a Teredo-riddled log lying in 1 m of water
      among mangrove roots, in Papua (New Guinea), whilst the second was found on an
      organically enriched beach at Sao Sebastiao (Brazil). In this contribution, a
      third species of Aracia is described from settling panels and red mangrove roots
      in an estuarine system located in southern Gulf of California (Mexico). The new
      species is a simultaneous hermaphrodite and brooder, unique in the presence of a
      rectangular ventral shield on the collar, shorter than those in posterior
      thoracic segments; and a high number of rows of teeth in thoracic and abdominal
      uncini, covering from one-half to three-quarters of the main fang length.
      Information about color patterns in live specimens, glandular patterns, and
      reproduction is provided. 

PMID- 24872063
TI  - A revision of the late Eocene snakeflies (Raphidioptera) of the Florissant
      Formation, Colorado, with special reference to the wing venation of the
      Raphidiomorpha.
AB  - The snakeflies (Raphidioptera) of the late Eocene Florissant Formation (Colorado,
      USA) are revised. Seven species of Raphidiidae are assigned to three genera,
      i.e., Megaraphidia Cockerell, 1907, Archiraphidia Handlirsch, 1910, and
      Florissantoraphidia gen. nov. Dictyoraphidia Handlirsch, 1910 is assigned to
      Baissopteridae, a first Cenozoic record of the family. Archiraphidia tumulata
      (Scudder, 1890), A. tranquilla (Scudder, 1890) and A.? somnolenta (Scudder,
      1890), stat. res. are treated as distinct species, and A. eventa (Scudder, 1890)
      as a new synonym of A. tranquilla. The lectotype of A. eventa is designated.
      'Raphidia' exhumata Cockerell, 1909 is transferred to Megaraphidia. 'Raphidia'
      mortua Rohwer, 1909 and 'R.' funerata Engel, 2003 constitute Florissantoraphidia
      gen. nov. Our findings support the treatment of the single Florissant species of
      Inocelliidae as preliminary assigned to Fibla Navas, 1915. We examine venational
      synapomorphies of Raphidiomorpha and provide a new diagnosis for it based on
      these characters. We evaluate putative derived venational character states of
      'Neoraphidioptera' (Inocelliidae and Raphidiidae), finding no clear synapomorphy
      supporting its validity; these families may nest separately within a paraphyletic
      Mesoraphidiidae (s.l.). We provide diagnoses for the families occurring at
      Florissant (Baissopteridae, Inocelliidae and Raphidiidae) based on wing venation.

PMID- 24872064
TI  - An updated and annotated checklist of the Dolichodoridae (Nematoda: Tylenchoidea)
      of Iran.
AB  - The list of plant parasitic nematodes of the family Dolichodoridae, known from
      Iran, is updated. 81 species belonging to 13 genera and three subfamilies are
      included in the list. Data for 29 species are added, of which seven species viz.
      Neodolichorhynchus phaseoli, Pratylenchoides crenicauda, P. erzurumensis, P.
      utahensis, Scutylenchus paniculoides, Trophurus impar and Tylenchorhynchus
      variannus are new records for the Iranian nematofauna. The list of species,
      further information on their morphometrics, references, referring to full or
      partial descriptions, associated plants, geographical distribution and some
      taxonomic remarks are provided. More detailed studies on some doubtful
      populations are proposed. The information on the taxonomic position of species in
      different classification schemes, as well as, the tendency of the species to
      certain climatic condition or ecological niche are provided. Challenges on the
      reliable identification of this group of nematodes in Iran are discussed and
      finally, suggestions were proposed for future studies. 

PMID- 24872065
TI  - A study on the genus Compsidolon Reuter, 1899 from China (Hemiptera: Heteroptera:
      Miridae: Phylinae), with descriptions of three new species.
AB  - Compsidolon Reuter from China with eleven species is reviewed here. Three of
      them, C. ailaoshanensis, C. flavidum, and C. pilosum are described as new to
      science. C. eximium (Reuter) is recorded from China for the first time.
      Compsidolon punctulatum Qi and Nonnaizab, 1995 is treated as a junior synonym of
      Compsidolon nebulosum (Reuter, 1878). A key to Chinese species of Compsidolon
      Reuter is given. Photographs of dorsal habitus, scanning electron micrographs of
      metathoracic scent-gland, and illustrations of male genitalia are also provided.
      All type specimens are deposited in the Institute of Entomology, Nankai
      University, Tianjin, China. 

PMID- 24872066
TI  - A new species and first record of the genus Shoemakerella Pirlot, 1936
      (Crustacea: Amphipoda: Lysianassidae) from Brazil.
AB  - A new species of the genus Shoemakerella Pirlot, 1936 is described for the
      Southeastern Brazilian continental shelf. The new species is easily recognized
      from the others in the genus mainly by the shape of the gnathopod 2. This is the
      first species of Shoemakerella from Brazilian waters. 

PMID- 24872067
TI  - A new species of Euchalcia Hubner, [1821] from Kazakhstan (Lepidoptera,
      Noctuidae).
AB  - The Holarctic genus Euchalcia Hubner, [1821] belongs to the tribe Plusiini of the
      subfamily Plusiinae. The genus is one of the largest in the Plusiinae, comprising
      about 54 described species. The systematics of Eurasian and North African members
      of the genus was recently revised (Ronkay et al. 2008). In June 2013, in the
      course of faunistic studies on Noctuidae of the Tarbagatai Mts. (East
      Kazakhstan), a long series of an undescribed species of the genus was collected.
      Two additional specimens from the Dzhungarsky Alatau Mts. (South-East Kazakhstan)
      were found in the collection of the Siberian Zoological Museum (Novosibirsk). The
      species is described herein as new. It belongs to the E. inconspicua group within
      the E. inconspicua species-complex (Ronkay et al. 2008). The E. inconspicua group
      comprises two described species only: E. inconspicua (Graeser, 1892) and E.
      anthea L. Ronkay, G. Ronkay & Behounek, 2008. The new species is the northernmost
      member of the group. Institutional acronyms are as follows: AVB-coll. A.V.
      Volynkin, Barnaul, Russia; MCK-coll. M. Cernila, Kamnik, Slovenia; NHMW
      Naturhistorisches Museum, Vienna, Austria; STP-coll. S.V. Titov, Pavlodar,
      Kazakhstan; SZMN-Siberian Zoological Museum of the Institute of Animal Systematic
      and Ecology of the Siberian Branch of the Russian Academy of Sciences
      (Novosibirsk, Russia), ZISP-Zoological Institute of Russian Academy of Sciences,
      St. Petersburg, Russia. 

PMID- 24872068
TI  - Revision of Mani's Figitidae types (Hymenoptera: Cynipoidea).

PMID- 24872069
TI  - Revision of the genus Apophua Morley, 1913, from Japan (Hymenoptera,
      Ichneumonidae, Banchinae).
AB  - Japanese species of the genus Apophua Morley, 1913, are revised. Eleven species
      are found from Japan and two of them, A. elegans sp. nov. and A. yamato sp. nov.,
      are newly described. Distribution data and an updated key to Japanese species are
      provided. 

PMID- 24872070
TI  - Four new species of the grass feeding leafhopper genus Nicolaus Lindberg
      (Hemiptera: Cicadellidae: Deltocephalinae) from the Indian subcontinent.
AB  - The leafhopper genus Nicolaus Lindberg is recorded from India and Pakistan for
      the first time. Four new species, N. abuensis sp. nov., N. bidentatus sp. nov.,
      N. cornutus sp. nov. and N. serratus sp. nov. are described and illustrated. N.
      bihamatus Xing & Li, earlier known from China is recorded from India and
      Pakistan. A key to the species of Nicolaus from the study area is provided. 

PMID- 24872072
TI  - Athanas manticolus sp. nov., a new stomatopod-associated alpheid shrimp from
      Vietnam (Crustacea, Decapoda).
AB  - A new species of the alpheid shrimp genus Athanas Leach, 1814 is described based
      on a single specimen, an ovigerous female from Nha Trang Bay, Vietnam. Athanas
      manticolus sp. nov. differs from all other species of Athanas by the presence of
      a small post-rostral tubercle, combined with a minutely toothed rostrum, reduced
      extra-corneal teeth, and the absence of infra-corneal and supra-corneal teeth. In
      addition, the new species is characterised by its unique colour pattern,
      particularly by the red chromatophores disposed in randomly oriented, short,
      narrow streaks. As its name suggests, A. manticolus sp. nov. is commensally
      associated with the burrows of the nannosquillid mantis shrimp Bigelowina
      phalangium (Fabricius, 1798). 

PMID- 24872071
TI  - The ancient Balkan lakes harbor a new endemic species of Diaphanosoma Fischer,
      1850 (Crustacea: Branchiopoda: Cladocera).
AB  - Diaphanosoma macedonicum sp. nov. is described from material collected from the
      ancient Lakes Dojran and Prespa, located in the central part of the Balkan
      Peninsula. It can be regarded as a member of the "D. mongolianum" species group.
      It is characterized by specific, but not readily visible features, such as the
      absence of a thorn near the posterior valve margins, as well as setules between
      setae of the ventral valve inflection, and the presence of more chitinized
      integument. The discovery of this new species previously identified as
      "Diaphanosoma brachyurum (Lievin)" highlights the necessity of more detailed
      investigations of the zooplankton of Balkan lakes potentially populated by
      greater numbers of endemic cladoceran species. A short overview of the ancient
      lakes in the Central Balkans is provided. 

PMID- 24872073
TI  - Two 'new' renicolid trematodes (Trematoda: Digenea: Renicolidae) from the
      California horn snail, Cerithidea californica (Haldeman, 1840) (Gastropoda:
      Potamididae).
AB  - This manuscript describes the daughter parthenitae (sporocysts) and cercariae of
      two species of renicolid xiphidiocercaria that infect the California horn snail,
      Cerithidea californica, which serves as first intermediate host for a diverse and
      ecologically important guild of digenean trematode parasitic castrators. The two
      species described here have previously been considered to be a single
      morphospecies in ecological and evolutionary research. We provide provisional
      species names to respect that digenean alpha taxonomy is currently focused on
      sexual (adult) stages, while simultaneously respecting the spirit and utility of
      formal nomenclature in providing unambiguously unique, species-level names that
      also clarify to the extent possible species' taxonomic affiliations. The first
      species, Renicola sp. "polychaetophila" is most readily distinguishable from
      previously described renicolid xiphidiocercariae by a combination of (1) having a
      penetration gland duct arrangement of 2[(1+3+1)+1], (2) having one pair of
      penetration glands positioned anteriorly to the main gland cluster, (3) lacking
      tegmental spines, and (4) infecting Cerithidea californica. The second species,
      Renicola sp. "martini", is most readily distinguishable from other renicolid
      xiphidiocercariae that also have tegmental spines by a combination of (1) having
      a simple, bullet-shaped oral stylet sclerotized for 50-80% of its length, (2)
      having a cystogenous-gland field with an anterior-most extent about half way
      between the oral and ventral suckers, and (3) in infecting Cerithidea
      californica. Phylogenetic analyses using DNA (COI and ITS1) sequence data support
      that these two trematodes represent distinct species of Renicola. We also (1)
      provide an emended diagnosis for renicolid cercariae, (2) highlight a few
      morphological characters that may be useful for future taxonomic work involving
      renicolid xiphidiocercariae, and (3) suggest that future descriptive work
      involving trematode parthenitae include more information pertaining to the group
      of parthenitae as a whole. 

PMID- 24872074
TI  - A new species of Microprosthema Stimpson, 1860 (Crustacea: Decapoda:
      Stenopodidea: Spongicolidae) from the South China Sea.
AB  - A new species of the spongicolid genus Microprosthema Stimpson, 1860 is described
      based on two specimens collected from Shi Island, Xisha Islands, South China Sea.
      The type specimens were collected within a sponge, representing an unusual
      habitat for the genus. M. personatum sp. nov. is easily distinguished from its
      closest congeners, M. takedai and M. fujitai, by its convex supraocular eaves and
      the number of teeth on the scaphocerite. A key to the Indo-West Pacific species
      of Microprosthema is given. 

PMID- 24872075
TI  - A new species of the genus Nothrholaspis Berlese (Acari: Macrochelidae) from
      Iran.
AB  - A new mite species of the genus Nothrholaspis Berlese, Nothrholaspis saboorii
      Babaeian & Joharchi sp. nov., is described and illustrated from specimens
      collected from soil in the Karaj region of Iran. An identification key for the
      known species of Nothrholaspis is presented. 

PMID- 24872076
TI  - Scanning electron microscopy of eggs of Georgecraigius fluviatilis (Lutz)
      (Diptera: Culicidae, Aedini).
AB  - Scanning Electron Microscopy was used to describe the eggs of Georgecraigius
      fluviatilis (Lutz). Length is 722.8+/-39.6 um and width is 177.1+/-9.8 um.
      Diameter of the micropylar disk, surrounded by an irregular flattened collar, is
      28 um. The outer chorionic sculpture consists of cells of irregular shapes,
      containing tubercles with pitted surface. In the ventral region, tubercles of
      several diameters are irregularly distributed in chorionic cells, while in the
      dorsal region one larger tubercle is surrounded by several smaller ones. The eggs
      appear to lack structures for adhesion, certainly unnecessary due to the habit of
      laying eggs separately on water surfaces. 

PMID- 24872077
TI  - A new species of Anarta Ochsenheimer, 1816 from Mongolian and Russian Altai
      (Lepidoptera, Noctuidae).
AB  - Anarta Ochsenheimer, 1816 is a hadenine genus restricted to Palaearctic and
      Nearctic Regions. The genus includes about 80 described species and subdivided
      into seven subgenera (Hacker 1998; Fibiger et al. 2011): Trichoclea Grote, 1883
      (= Hadula Staudinger, 1889), Cardiestra Boursin, 1963, Ptochicestra Hacker, 1998,
      Aglossestra Hampson, 1905, Calocestra Beck, 1991, Pulchrohadula Hacker, 1998 and
      Anarta Ochsenheimer, 1816 (= Discestra Hampson, 1905). The group has been revised
      by Hacker (1998). Anarta, Trichoclea, Hadula and Discestra were been synonymized
      by Fibiger & Hacker (2005). 

PMID- 24872078
TI  - Amplitude-oriented exercise in Parkinson's disease: a randomized study comparing
      LSVT-BIG and a short training protocol.
AB  - LSVT-BIG is an exercise for patients with Parkinson's disease (PD) comprising of
      16 1-h sessions within 4 weeks. LSVT-BIG was compared with a 2-week short
      protocol (AOT-SP) consisting of 10 sessions with identical exercises in 42
      patients with PD. UPDRS-III-score was reduced by -6.6 in LSVT-BIG and -5.7 in AOT
      SP at follow-up after 16 weeks (p < 0.001). Measures of motor performance were
      equally improved by LSVT-BIG and AOT-SP but high-intensity LSVT-BIG was more
      effective to obtain patient-perceived benefit.

PMID- 24872080
TI  - Monitoring enzymatic ATP hydrolysis by EPR spectroscopy.
AB  - An adenosine triphosphate (ATP) analogue modified with two nitroxide radicals is
      developed and employed to study its enzymatic hydrolysis by electron paramagnetic
      resonance spectroscopy. For this application, we demonstrate that EPR holds the
      potential to complement fluorogenic substrate analogues in monitoring enzymatic
      activity. 

PMID- 24872079
TI  - Endogenous serotonin facilitates hippocampal long-term potentiation at CA3/CA1
      synapses.
AB  - Encoding of episodic memory requires long-term potentiation (LTP) of
      neurotransmission at excitatory synapses of the hippocampal circuitry. Previous
      data obtained with the application of exogenous 5-hydroxytryptamine (5-HT) in
      hippocampal slices indicate that 5-HT blocks LTP, which contrasts with the
      facilitatory effect of selective serotonin reuptake inhibitors (SSRIs) on
      learning and memory observed in vivo. Here, we investigated the effects of
      endogenous 5-HT, released from terminals by the monoamine releaser 3,4
      methylenedioxymethamphetamine (MDMA), on LTP of field EPSPs induced by theta
      burst stimulation and recorded at CA3/CA1 synapses of rat hippocampal slices. LTP
      was greater in the presence of MDMA (10 uM; 45.76 +/- 15.75%; n = 28) than in
      controls (31.26 +/- 11.03; n = 21; p < 0.01). This facilitatory effect on LTP
      persisted when the entry of MDMA in noradrenergic terminals was prevented by the
      selective noradrenaline reuptake inhibitor nisoxetine (44.90 +/- 14.07%; n = 27
      vs. 34.49 +/- 12.94%; n = 20 in controls; p < 0.05). In both conditions, the
      facilitation of LTP was abolished by the SSRI citalopram that prevented the entry
      of MDMA in 5-HT terminals and the subsequent 5-HT release. These data show that,
      unlike exogenous 5-HT application, release of endogenous 5-HT does not impair
      cellular mechanisms responsible for induction of LTP, indicating that 5-HT is not
      detrimental to learning and memory. Moreover, facilitation of LTP by endogenous 5
      HT may underlie the in vivo positive effects of augmented 5-HT tone on cognitive
      performance.

PMID- 24872081
TI  - Involvement of miR-196a in HIV-associated neurocognitive disorders.
AB  - Involvement of the human immunodeficiency virus type 1 (HIV-1) trans-activator of
      transcription (Tat) protein in neuronal deregulation and in the development of
      HIV-1 associated neurocognitive disorders (HAND) has been amply explored; however
      the mechanisms involved remain unclear. In search for the mechanisms, we
      demonstrated that Tat deregulates neuronal functions through a pathway that
      involved p73 and p53 pathway. We showed that Tat uses microRNA-196a (miR-196a) to
      deregulate the p73 pathway. Further, we found that the Abelson murine leukemia (c
      Abl) phosphorylates p73 on tyrosine residue 99 (Tyr-99) in Tat-treated cells.
      Interestingly, Tat lost its ability to promote accumulation and phosphorylation
      of p73 in the presence of miR-196a mimic. Interestingly, accumulation of p73 did
      not lead to neuronal cell death by apoptosis as obtained by cell viability assay.
      Western blot analysis using antibodies directed against serine residues 807 and
      811 of retinoblastoma (Rb) protein was also used to validate our data regarding
      lack of cell death. Hyperphosphorylation of RB (S807/811) is an indication of
      cell neuronal viability. These results highlight the key role played by p73 and
      microRNA in Tat-treated neurons leading to their deregulation and it deciphers
      mechanistically one of the pathways used by Tat to cause neuronal dysfunction
      that contributes to the development of HAND.

PMID- 24872082
TI  - Anti-apoptotic therapeutic approaches in liver diseases: do they really make
      sense?
AB  - A variety of data suggesting apoptotic cell death as a key feature of liver
      injury stimulated researchers to investigate the therapeutic potential of anti
      apoptotic strategies in experimental models. However, the overestimated role of
      apoptotic cell death in liver injury has tempered the clinical translation of the
      protection afforded by anti-apoptotic regimes in experimental models. Thus, the
      hope for apoptosis modulation as potential treatment strategy for injured liver
      in humans could not be confirmed. Herein, we evaluated the degree of apoptosis in
      different hepatic stress models which are relevant for the human pathophysiology.
      Using morphological criteria of apoptosis, caspase-3 activation as well as TUNEL
      assay in combination with a positive control of apoptosis in liver injury, we
      quantified apoptotic cell death discriminating between parenchymal and non
      parenchymal cells and confirmed these results by cleaved caspase-3 and PARP-1
      protein expression. Discussing our findings and relating them to the existing
      literature on the potential role of apoptotic cell death, we strongly recommend
      reconsidering anti-apoptotic strategies to ameliorate liver injury efficiently.

PMID- 24872083
TI  - Regulation of adipocyte lipolysis.
AB  - In adipocytes the hydrolysis of TAG to produce fatty acids and glycerol under
      fasting conditions or times of elevated energy demands is tightly regulated by
      neuroendocrine signals, resulting in the activation of lipolytic enzymes. Among
      the classic regulators of lipolysis, adrenergic stimulation and the insulin
      mediated control of lipid mobilisation are the best known. Initially, hormone
      sensitive lipase (HSL) was thought to be the rate-limiting enzyme of the first
      lipolytic step, while we now know that adipocyte TAG lipase is the key enzyme for
      lipolysis initiation. Pivotal, previously unsuspected components have also been
      identified at the protective interface of the lipid droplet surface and in the
      signalling pathways that control lipolysis. Perilipin, comparative gene
      identification-58 (CGI-58) and other proteins of the lipid droplet surface are
      currently known to be key regulators of the lipolytic machinery, protecting or
      exposing the TAG core of the droplet to lipases. The neuroendocrine control of
      lipolysis is prototypically exerted by catecholaminergic stimulation and insulin
      induced suppression, both of which affect cyclic AMP levels and hence the protein
      kinase A-mediated phosphorylation of HSL and perilipin. Interestingly, in recent
      decades adipose tissue has been shown to secrete a large number of adipokines,
      which exert direct effects on lipolysis, while adipocytes reportedly express a
      wide range of receptors for signals involved in lipid mobilisation. Recently
      recognised mediators of lipolysis include some adipokines, structural membrane
      proteins, atrial natriuretic peptides, AMP-activated protein kinase and mitogen
      activated protein kinase. Lipolysis needs to be reanalysed from the broader
      perspective of its specific physiological or pathological context since basal or
      stimulated lipolytic rates occur under diverse conditions and by different
      mechanisms. 

PMID- 24872084
TI  - The role of renal denervation in the treatment of hypertension.
AB  - OPINION STATEMENT: Resistant hypertension remains a difficult clinical disease to
      treat. It is known to place a patient at higher risk for developing significant
      cardiovascular, renal, and cerebrovascular disease. There is a current surge in
      research investigating renal denervation as potential treatment for resistant
      hypertension, as an overactive renal sympathetic system is known to exert an
      influence on the underlying pathophysiology. Several small studies have been
      published, with more underway, evaluating multiple different catheter-based
      systems that utilize radiofrequency ablation or ultrasound wave energy. These
      studies are showing promising results, with reduction in office blood pressure
      for the majority of patients. However, it appears that this does not always
      translate into definitive real-world observational effects. Variability exists in
      the number of patients that are able to reduce the amount of medication they take
      for hypertension, with some requiring an increase in medication. As a result, a
      more intensive screening process has been proposed, evaluating specific key
      predictors that may translate into a more favorable clinical response to renal
      denervation. We recommend that individuals with resistant hypertension continue
      to be optimized medically, adequately screened for secondary causes of
      hypertension, and that they consider participation in a renal denervation
      clinical trial to aid in further advancing the field.

PMID- 24872086
TI  - Fat grafting in immediate breast reconstruction. Avoiding breast sequelae.
AB  - BACKGROUND: The remarkable increase that breast-conserving surgery has been
      experiencing throughout the last decades is as much undeniable as the imposition
      of the immediate reconstruction as the gold-standard treatment regarding breast
      reconstruction. Nevertheless, these trends conflict since we do not have a
      satisfactory immediate reconstruction method for breast-conserving surgery. This
      work shows the technique we have developed to solve this problem through
      autologous fat grafting ensuring the same oncological safety. METHODS: We present
      the preliminary results of 37 immediate reconstructions of lumpectomies and
      quadrantectomies through autologous fat grafting of lumpectomies. Patients have
      been chosen by a multidisciplinary committee following special criteria based on
      their low-risk pathology, having undergone different diagnostic tests previous to
      the resection and 1 year postoperative monitoring by qualified observers. Also, a
      satisfaction survey has been performed. RESULTS: In all cases studied, with a
      year follow-up, we found excellent aesthetic outcomes with no presence of the
      feared scar retractions and deformities, even after radiotherapy. According to
      patient surveys, the satisfaction rate was also very high. No important
      complications, either acute or chronic, have been observed from the
      implementation of this technique. CONCLUSION: This is a useful, innovative
      technique, having good aesthetic results, decreasing the incidence of aesthetic
      sequelae, commonly seen in simple lumpectomies without reconstruction. The
      complication rate is low, and oncological safety is not compromised.

PMID- 24872087
TI  - Clinical significance of FDG-PET/CT at the postoperative surveillance in the
      breast cancer patients.
AB  - AIM: We evaluated the clinical role of [(18)F]-2-fluoro-2-deoxy-D-glucose
      positron emission tomography/computed tomography (FDG-PET/CT) compared with
      conventional imaging (CI) to detect locoregional recurrence or distant metastasis
      during postoperative surveillance of patients with breast cancer. MATERIALS AND
      METHODS: We included 1,819 examinations of 1,161 patients, who underwent FDG
      PET/CT and CI, including mammography, breast ultrasound, whole-body bone
      scintigraphy, and chest radiography for postoperative surveillance. All patients
      had a history of surgery with or without adjuvant treatment due to more than
      stage II breast cancer between November 2003 and November 2009. We evaluated the
      diagnostic performance of CI, FDG-PET/CT, and combined CI and FDG-PET/CT for
      detecting locoregional recurrence, distant metastasis, and incidental cancer. We
      also analyzed false-positive and false-negative results in both FDG-PET/CT and
      CI. RESULTS: Sensitivity, specificity, positive predictive value, and negative
      predictive value of CI were 75.4, 98.7, 93.4, and 94.3 %. Those of FDG-PET/CT
      were 97.5, 98.8, 95.4, and 99.4 %. Those of the combined results were 98.6, 98.2,
      96.7, and 99.7 %. Sensitivity of FDG-PET/CT was significantly higher than that of
      CI (P < 0.05). Sensitivity of combined CI and FDG-PET/CT results improved, but
      they were not significantly different from those of FDG-PET/CT alone (P = 0.43).
      Seventeen false-positive and nine false-negative cases were detected with FDG
      PET/CT, and 19 false-positive and 88 false-negative cases were detected with CI.
      CONCLUSION: FDG-PET/CT is considered as an acceptable diagnostic imaging modality
      for postoperative surveillance of patients with breast cancer.

PMID- 24872092
TI  - Effective coarse-grained solid-fluid potentials and their application to model
      adsorption of fluids on heterogeneous surfaces.
AB  - The use of effective fluid-surface potentials, in which the full positional
      dependence is replaced by a dependence only on the distance from the surface of
      the solid, is common practice as a route to reduce the complexity of evaluating
      adsorption of fluids on substrates. Conceptually this is equivalent to replacing
      the detailed description of the discrete molecular nature by a coarse-grained
      description in which the solid is represented by a continuous (structureless)
      surface. These effective fluid-surface potentials are essential in the
      development of theories for surface adsorption, and they provide a means to
      reduce the computational cost associated with the molecular simulation of the
      system. The main purpose of the present contribution is to emphasise the
      necessity of using an adequate averaging procedure to obtain effective fluid
      surface potentials. A simple unweighted average of the configurational energy is
      commonly employed, resulting in effective potentials that are temperature
      independent. We describe here a procedure to develop free-energy-averaged
      effective fluid-surface potentials retaining the important temperature dependence
      of the coarse-grained interaction between the particle and the surface. Although
      the approach is general in nature, we assess the merits of free-energy-averaged
      potentials for the adsorption of methane on graphene and graphite, making
      appropriate comparisons with the description obtained with the more traditional
      temperature-independent potentials. Additionally, we develop effective fluid
      surface potentials for crystalline faces of monolayer and multilayer homogeneous
      and heterogeneous fcc lattices based on the Lennard-Jones (12-6) pair potential,
      and compute the corresponding adsorption isotherms of Lennard-Jones fluids on
      these surfaces using Grand Canonical Monte Carlo (GCMC) simulations. The adequacy
      of the two different options to obtain effective fluid-surface potentials (a free
      energy-based versus a simple unweighted average) is compared critically. It is
      shown here that the higher the heterogeneity of the surface the less adequate
      simple unweighted averages are to describe the adsorption behaviour in comparison
      to free-energy averages. 

PMID- 24872093
TI  - UK pharmaceutical industry under threat.

PMID- 24872085
TI  - Increased 1-year healthcare use in survivors of severe sepsis.
AB  - RATIONALE: Hospitalizations for severe sepsis are common, and a growing number of
      patients survive to hospital discharge. Nonetheless, little is known about
      survivors' post-discharge healthcare use. OBJECTIVES: To measure inpatient
      healthcare use of severe sepsis survivors compared with patients' own presepsis
      resource use and the resource use of survivors of otherwise similar nonsepsis
      hospitalizations. METHODS: This is an observational cohort study of survivors of
      severe sepsis and nonsepsis hospitalizations identified from participants in the
      Health and Retirement Study with linked Medicare claims, 1998-2005. We matched
      severe sepsis and nonsepsis hospitalizations by demographics, comorbidity burden,
      premorbid disability, hospitalization length, and intensive care use.
      MEASUREMENTS AND MAIN RESULTS: Using Medicare claims, we measured patients' use
      of inpatient facilities (hospitals, long-term acute care hospitals, and skilled
      nursing facilities) in the 2 years surrounding hospitalization. Severe sepsis
      survivors spent more days (median, 16 [interquartile range, 3-45] vs. 7 [0-29]; P
      < 0.001) and a higher proportion of days alive (median, 9.6% [interquartile
      range, 1.4-33.8%] vs. 1.9% [0.0-7.9%]; P < 0.001) admitted to facilities in the
      year after hospitalization, compared with the year prior. The increase in
      facility-days was similar for nonsepsis hospitalizations. However, the severe
      sepsis cohort experienced greater post-discharge mortality (44.2% [95% confidence
      interval, 41.3-47.2%] vs. 31.4% [95% confidence interval, 28.6-34.2%] at 1 year),
      a steeper decline in days spent at home (difference-in-differences, -38.6 d [95%
      confidence interval, -50.9 to 26.3]; P < 0.001), and a greater increase in the
      proportion of days alive spent in a facility (difference-in-differences, 5.4%
      [95% confidence interval, 2.8-8.1%]; P < 0.001). CONCLUSIONS: Healthcare use is
      markedly elevated after severe sepsis, and post-discharge management may be an
      opportunity to reduce resource use.

PMID- 24872094
TI  - Breast cancer in older women: predicting adjuvant benefit.

PMID- 24872095
TI  - Origins research in large cell lymphoma-time for action?

PMID- 24872096
TI  - Carboplatin for early triple-negative breast cancer?

PMID- 24872097
TI  - Baseline standards for paediatric oncology nursing care in low to middle income
      countries: position statement of the SIOP PODC Nursing Working Group.

PMID- 24872098
TI  - (18)F-FDG PET/CT scans for children and adolescents.

PMID- 24872099
TI  - Full-spectrum colonoscopy for adenoma detection.

PMID- 24872100
TI  - (18)F-FDG PET/CT scans for children and adolescents - authors' reply.

PMID- 24872101
TI  - Full-spectrum colonoscopy for adenoma detection - author reply.

PMID- 24872102
TI  - Stereotactic radiosurgery for patients with brain metastases.

PMID- 24872103
TI  - Stereotactic radiosurgery for patients with brain metastases.

PMID- 24872104
TI  - Stereotactic radiosurgery for patients with brain metastases - authors' reply.

PMID- 24872105
TI  - Carboplatin plus paclitaxel scheduling for advanced ovarian cancer.

PMID- 24872106
TI  - Carboplatin plus paclitaxel scheduling for advanced ovarian cancer.

PMID- 24872107
TI  - Carboplatin plus paclitaxel scheduling for advanced ovarian cancer - authors'
      reply.

PMID- 24872108
TI  - Rituximab for follicular lymphoma: watch and wait, watch and worry, or watch and
      live?

PMID- 24872109
TI  - Clinical use of dendritic cells for cancer therapy.
AB  - Since the mid-1990s, dendritic cells have been used in clinical trials as
      cellular mediators for therapeutic vaccination of patients with cancer. Dendritic
      cell-based immunotherapy is safe and can induce antitumour immunity, even in
      patients with advanced disease. However, clinical responses have been
      disappointing, with classic objective tumour response rates rarely exceeding 15%.
      Paradoxically, findings from emerging research indicate that dendritic cell-based
      vaccination might improve survival, advocating implementation of alternative
      endpoints to assess the true clinical potency of dendritic cell-based
      vaccination. We review the clinical effectiveness of dendritic cell-based vaccine
      therapy in melanoma, prostate cancer, malignant glioma, and renal cell carcinoma,
      and summarise the most important lessons from almost two decades of clinical
      studies of dendritic cell-based immunotherapy in these malignant disorders. We
      also address how the specialty is evolving, and which new therapeutic concepts
      are being translated into clinical trials to leverage the clinical effectiveness
      of dendritic cell-based cancer immunotherapy. Specifically, we discuss two main
      trends: the implementation of the next-generation dendritic cell vaccines that
      have improved immunogenicity, and the emerging paradigm of combination of
      dendritic cell vaccination with other cancer therapies. 

PMID- 24872110
TI  - Classification of endometrial carcinoma: more than two types.
AB  - Endometrial cancer is the most common gynaecological malignancy in Europe and
      North America. Traditional classification of endometrial carcinoma is based
      either on clinical and endocrine features (eg, types I and II) or on
      histopathological characteristics (eg, endometrioid, serous, or clear-cell
      adenocarcinoma). Subtypes defined by the different classification systems
      correlate to some extent, but there is substantial heterogeneity in biological,
      pathological, and molecular features within tumour types from both classification
      systems. In this Review we provide an overview of traditional and newer genomic
      classifications of endometrial cancer. We discuss how a classification system
      that incorporates genomic and histopathological features to define biologically
      and clinically relevant subsets of the disease would be useful. Such integrated
      classification might facilitate development of treatments tailored to specific
      disease subgroups and could potentially enable delivery of precision medicine to
      patients with endometrial cancer. 

PMID- 24872111
TI  - Breast cancer in China.
AB  - The health burden of cancer is increasing in China, with more than 1.6 million
      people being diagnosed and 1.2 million people dying of the disease each year. As
      in most other countries, breast cancer is now the most common cancer in Chinese
      women; cases in China account for 12.2% of all newly diagnosed breast cancers and
      9.6% of all deaths from breast cancer worldwide. China's proportional
      contribution to global rates is increasing rapidly because of the population's
      rising socioeconomic status and unique reproductive patterns. In this Review we
      present an overview of present control measures for breast cancer across China,
      and emphasise epidemiological and socioeconomic diversities and disparities in
      access to care for various subpopulations. We describe demographic differences
      between China and high-income countries, and also within geographical and
      socioeconomic regions of China. These disparities between China and high-income
      countries include younger age at onset of breast cancer; the unique one-child
      policy; lower rates of provision and uptake for screening for breast cancer;
      delays in diagnosis that result in more advanced stage of disease at
      presentation; inadequate resources; and a lack of awareness about breast cancer
      in the Chinese population. Finally, we recommend key measures that could
      contribute to improved health outcomes for patients with breast cancer in China. 

PMID- 24872112
TI  - Cancer in refugees in Jordan and Syria between 2009 and 2012: challenges and the
      way forward in humanitarian emergencies.
AB  - Treatment of non-communicable diseases such as cancer in refugees is neglected in
      low-income and middle-income countries, but is of increasing importance because
      the number of refugees is growing. The UNHCR, through exceptional care committees
      (ECCs), has developed standard operating procedures to address expensive medical
      treatment for refugees in host countries, to decide on eligibility and amount of
      payment. We present data from funding applications for cancer treatments for
      refugees in Jordan between 2010 and 2012, and in Syria between 2009 and 2011.
      Cancer in refugees causes a substantial burden on the health systems of the host
      countries. Recommendations to improve prevention and treatment include
      improvement of health systems through standard operating procedures and
      innovative financing schemes, balance of primary and emergency care with
      expensive referral care, development of electronic cancer registries, and
      securement of sustainable funding sources. Analysis of cancer care in low-income
      refugee settings, particularly in sub-Saharan Africa, is needed to inform future
      responses. 

PMID- 24872113
TI  - Gadolinium-based nanoparticles for highly efficient T1-weighted magnetic
      resonance imaging.
AB  - We developed Pyrene-Gadolinium (Py-Gd) nanoparticles as pH-sensitive magnetic
      resonance imaging (MRI) contrast agents capable of showing a high-Mr signal in
      cancer-specific environments, such as acidic conditions. Py-Gd nanoparticles were
      prepared by coating Py-Gd, which is a complex of gadolinium with pyrenyl
      molecules, with pyrenyl polyethyleneglycol PEG using a nano-emulsion method.
      These particles show better longitudinal relaxation time (T1) MR signals in
      acidic conditions than they do in neutral conditions. Furthermore, the particles
      exhibit biocompatibility and MR contrast effects in both in vitro and in vivo
      studies. From these results, we confirm that Py-Gd nanoparticles have the
      potential to be applied for accurate cancer diagnosis and therapy.

PMID- 24872116
TI  - New aspects of IgA synthesis in the gut.
AB  - In mammals, the gastrointestinal tract is colonized by extremely dense and
      diverse bacterial communities that are beneficial for health. Maintenance of the
      complexity and the proper localization and distribution of gut bacteria is of
      prime importance because when disrupted, the microbial community attacks the
      host's tissues and causes inflammatory reactions. Our immune system provides the
      necessary mechanisms to maintain the homeostatic balance between microbial
      communities and the host. IgA plays crucial roles in regulation of host-bacteria
      interactions in the gut. IgA is the most abundant immunoglobulin isotype in our
      body, mostly produced by the IgA plasma cells residing in the lamina propria of
      the small and large intestine. Although it was well known that IgA provides
      protection against pathogens, only recently has it become clear that IgA plays
      critical roles in regulation of bacterial communities in the gut in steady-state
      conditions. Here, we summarize recent progress in our understanding of the
      various mechanisms of IgA synthesis in multiple anatomical sites and discuss how
      IgA limits bacterial access to the internal milieu of the host. 

PMID- 24872114
TI  - Controlling cytomegalovirus: helping the immune system take the lead.
AB  - Cytomegalovirus, of the Herpesviridae family, has evolved alongside humans for
      thousands of years with an intricate balance of latency, immune evasion, and
      transmission. While upwards of 70% of humans have evidence of CMV infection, the
      majority of healthy people show little to no clinical symptoms of primary
      infection and CMV disease is rarely observed during persistent infection in
      immunocompetent hosts. Despite the fact that the majority of infected individuals
      are asymptomatic, immunologically, CMV hijacks the immune system by infecting and
      remaining latent in antigen-presenting cells that occasionally reactivate
      subclinically and present antigen to T cells, eventually causing the inflation of
      CMV-specific T cells until they can compromise up to 10% of the entire T cell
      repertoire. Because of this impact on the immune system, as well as its
      importance in fields such as stem cell and organ transplant, the relationship
      between CMV and the immune response has been studied in depth. Here we provide a
      review of many of these studies and insights into how CMV-specific T cells are
      currently being used therapeutically. 

PMID- 24872115
TI  - Hemispheric side of damage influences sex-related differences in smoking
      cessation in neurological patients.
AB  - Patterns of smoking behavior vary between the sexes. There is evidence that
      decision making, which is one of the key "executive functions" necessary for
      making life-style modifications such as smoking cessation, is relatively
      lateralized to the right hemisphere in males and left hemisphere in females. In
      the current study, we examined whether the side of brain lesion has a
      differential effect on smoking behavior between the sexes. We hypothesized sex
      differences in smoking cessation based on lesion side. Participants were 49 males
      and 50 females who were smoking at the time of lesion onset. The outcome variable
      was abstinence from smoking (quit rate) at least one year post lesion. We found
      that in patients with left-hemisphere damage, quit rates were significantly
      higher in males than in females; however, in patients with right-hemisphere
      damage, quit rates were not statistically different. The findings support
      previous cognitive neuroscience literature showing that components of behavior
      responsible for maintaining addiction tend to be more strongly lateralized in
      males, whereas in females there is a more bilateral distribution. Our study
      provides further evidence for differences in lateralization of complex behavior
      between the sexes, which has significant implications for differences in
      treatment strategies between the sexes. 

PMID- 24872117
TI  - Prophylactic plastic surgery closure of neurosurgical scalp incisions reduces the
      incidence of wound complications in previously-operated patients treated with
      bevacizumab (Avastin(r)) and radiation.
AB  - Neurosurgical craniotomy, craniectomy, or other trans-galeal interventions are
      performed for a variety of indications, including the resection of benign or
      malignant tumors, hematoma evacuation, and for the management of intractable
      seizure disorders. Despite an overall low complication rate of intervention,
      wound healing complications such as dehiscence, surgical site infection, and
      cerebrospinal fluid leak are not uncommon. A retrospective review was performed
      of all patients who underwent scalp incision closure at a single institution by a
      single plastic surgeon between 2006 and 2013. Sixty patients (83 procedures) were
      included in the study. Fifty-seven patients (95.0 %) underwent previous
      craniotomy, craniectomy, or other trans-galeal procedure. Of the total 60
      patients, 35 patients received preoperative radiation. Sixteen patients received
      bevacizumab prior to their index case, while 12 received bevacizumab
      postoperatively. Ten patients (16.7 %) required additional plastic surgical
      intervention for wound complications after their index plastic surgery procedure.
      Plastic surgery was consulted prophylactically in 34 patients (38 procedures).
      When plastic surgery was consulted prophylactically, 4 patients (11.8 %) required
      further wound revision. None of the 14 patients who underwent prophylactic
      plastic surgery closure for previous scalp incision, preoperative bevacizumab,
      and XRT administration required re-intervention. Plastic surgery closure of
      complex scalp incisions reduces the incidence of wound complications among
      patients who underwent previous neurosurgical intervention, XRT administration,
      and preoperative bevacizumab administration. This is particularly true when
      plastic surgery closure is performed "prophylactically." Further collaboration
      between the neurosurgical and plastic surgery teams is therefore warranted,
      particularly in the setting of these high-risk cases.

PMID- 24872118
TI  - Facile synthesis of fluorescent active triazapentalenes through gold-catalyzed
      triazole-alkyne cyclization.
AB  - Fluorescent active triazapentalene zwitterions (TAPZs) were prepared through
      Au(I) catalyzed triazole-alkyne 5-endo-dig cyclization. While an effective gold
      catalyst turnover (0.5% loading, up to 96% yield) was achieved, the stability of
      these new 10-pi-electron bicyclic structures was also significantly improved,
      which warranted future applications of these fluorescent dyes.

PMID- 24872119
TI  - A peer adherence support intervention to improve the antiretroviral treatment
      outcomes of HIV patients in South Africa: the moderating role of family dynamics.
AB  - Given the severe shortage of human resources in the healthcare sector in many
      countries with high HIV prevalence, community-based peer adherence support is
      being increasingly cited as an integral part of a sustainable antiretroviral
      treatment (ART) strategy. However, the available scientific evidence on this
      topic reports discrepant findings on the effectiveness of peer adherence support
      programmes. These conflicting findings to some extent can be attributed to the
      lack of attention to the social contexts in which peer adherence support
      programmes are implemented. This study explores the potential moderating role of
      family dynamics by assessing the differential impact of peer adherence support in
      different types of families, based on the theoretical underpinnings of the family
      functioning framework. These relationships were explored with the aid of
      multivariate statistical analysis of cross-sectional, post-trial data for a
      sample of 340 patients interviewed as part of the Effectiveness of Aids Treatment
      and Support in the Free State (FEATS) study conducted in the public-sector ART
      programme of the Free State Province of South Africa. The analysis reveals no
      significant overall differences in CD4 cell count between the intervention group
      accessing additional peer adherence support and the control group receiving
      standard care. When controlling for the potential moderating role of family
      dynamics, however, the outcomes clearly reveal a significant interaction effect
      between the adherence intervention and the level of family functioning with
      regard to treatment outcomes. Multi-group analysis demonstrates that peer
      adherence support has a positive effect on immunological restoration in well
      functioning families, while having a negative effect in dysfunctional families.
      The study outcomes stress the need for peer adherence interventions that are
      sensitive to the suboptimal contexts in which they are often implemented.
      Generic, broad-based interventions do not necessarily facilitate the treatment
      adherence of the most vulnerable patient groups, particularly those without
      supportive family contexts. Tailoring interventions aimed at creating a health
      enabling environment to the needs of these at-risk patients should therefore be a
      priority for both research and policy.

PMID- 24872121
TI  - Trans fatty acid content in Malaysian supermarket foods: a field-to-laboratory
      approach in assessing food risk.
AB  - The extent of industrial trans fatty acids (TFA) in the food supply is unknown in
      Malaysia, whilst TFA disclosure on food labels is not mandatory by Malaysian food
      standards. Supermarket foods such as dairy products, fats and oils, meat
      products, snack foods, soups, and confectionery are commonly cited to be major
      contributors of TFA in the diet. A consumer survey (n = 622) was used to develop
      a food listing of these 'high risk' foods. TFA content of high-risk foods were
      analysed by gas chromatography. Food samples (n = 158) were analysed and their
      total TFA content were compared with Malaysian Food Standards. A wide variation
      in TFA content within food categories was indicated. Of the foods containing TFA,
      many food labels did not cite TFA content or the use of partially hydrogenated
      vegetable oils (PHVO) as an ingredient. Hypothesised estimates of TFA intake from
      these supermarket foods in a sample day's menu providing 2000 kcal projected a
      minimum intake of 0.5 g and a maximum intake of 5.2 g TFA. This study found there
      was no voluntary disclosure of TFA content on food labels or identifying PHVO as
      an ingredient. It appears that health education targeting consumers to minimise
      TFA consumption is required supported by mandatory PHVO disclosure on the food
      label. 

PMID- 24872122
TI  - Chiral Bronsted acid catalyzed enantioselective intermolecular allylic
      aminations.
AB  - This paper describes an enantioselective intermolecular allylic amination
      catalyzed by a chiral Bronsted acid via a possible chiral contact ion pair
      intermediate. A variety of symmetrical or unsymmetrical allylic alcohols can be
      smoothly aminated to afford the desired products in moderate to high yields with
      good enantioselectivities and/or regioselectivities. 

PMID- 24872123
TI  - Creation and initial assessment of a second-trimester uterine model.
AB  - INTRODUCTION: Training for obstetrics and gynecology residents in second
      trimester dilation and evacuation (D&E) procedures is extremely limited despite
      the Accreditation Council for Graduate Medical Education mandating all residents
      to receive abortion training. Simulation-based training improves surgical
      competence, but no second-trimester uterine models exist. The purposes of this
      study were to create a realistic, low-cost model and to assess the prototype.
      METHODS: A uterine model was created with 6 silicone cervixes of varying texture
      and dilations that are interchangeable. The uterus is neoprene and opens to allow
      for objects to be placed within it for extraction. At a national meeting,
      experienced D&E surgeons assessed the prototype by using the model and then
      completing a questionnaire. RESULTS: Twenty-one expert surgeons completed the
      questionnaires. Participants rated the prototype as "useful" or "very useful" for
      teaching extraction skills and for training in general. Subjects agreed this
      represented a clinical scenario they were likely to encounter and the model
      allowed for practicing the necessary steps for performing D&Es. The model cost
      approximately $35 to fabricate. CONCLUSIONS: Expert surgeons believe that this
      model accurately and realistically replicates a second-trimester uterus and
      cervix. This prototype may be used in simulation environments to train obstetrics
      and gynecology residents.

PMID- 24872120
TI  - Cytokine gene associations with self-report ratings of morning and evening
      fatigue in oncology patients and their family caregivers.
AB  - The purpose of this study was to evaluate for differences in variations in pro-
      and anti-inflammatory cytokine genes between participants who were classified as
      having low and high levels of morning and evening fatigue and to evaluate for
      differences in phenotypic characteristics between these two groups. In a sample
      of 167 oncology outpatients with breast, prostate, lung, or brain cancer and 85
      of their family caregivers, growth mixture modeling was used to identify latent
      classes of individuals based on ratings of morning and evening fatigue obtained
      prior to, during, and for 4 months following completion of radiation therapy.
      Differences in single nucleotide polymorphisms and haplotypes in 15 cytokine
      genes were evaluated between the latent classes. Multiple logistic regression was
      used to assess the effect of phenotypic and genotypic characteristics on morning
      and evening fatigue class membership. Associations were found between morning
      fatigue and number of comorbidities as well as variations in tumor necrosis
      factor alpha (TNFA) rs1800629 and rs3093662. Evening fatigue was associated with
      caring for children at home and variations in interleukin 4 (IL4) rs2243248 and
      TNFA rs2229094. Younger age and lower performance status were associated with
      both morning and evening fatigue. These findings suggest that inflammatory
      mediators are associated with the development of morning and evening fatigue.
      However, because different phenotypic characteristics and genomic markers are
      associated with diurnal variations in fatigue, morning and evening fatigue may be
      distinct but related symptoms. 

PMID- 24872124
TI  - Call for a randomized controlled trial: early glycemic control in the development
      of retinopathy of prematurity.

PMID- 24872125
TI  - Benign frontal horn cysts in a preterm neonate.

PMID- 24872126
TI  - Late-onset Ochrobactrum anthropi sepsis in a preterm neonate with congenital
      urinary tract abnormalities.
AB  - Recent trends in late-onset neonatal sepsis have revealed an increase in Gram
      negative organisms as causative agents. Ochrobactrum anthropi is an emerging
      human pathogen that has been reported primarily in immunocompromised hosts,
      especially those with indwelling catheters or other medical devices. We report
      the occurrence of late-onset urosepsis secondary to O. anthropi in a preterm
      neonate with posterior urethral valves and review the salient features of the
      pathogen and its management. 

PMID- 24872127
TI  - Treatment with bisphosphonates in severe hypercalcemia due to subcutaneous fat
      necrosis in an infant with hypoxic-ischemic encephalopathy.
AB  - Subcutaneous fat necrosis (SCFN) is a rare entity that occurs generally in term
      or post-term newborns exposed to perinatal stressing factors. These cutaneous
      lesions appear during the first weeks of life and their potential complications,
      such as hypercalcemia, determine the prognosis. We present a full-term newborn
      with SCFN lesions that appeared at the age of 12 days and who, 1 week later,
      developed moderate hypercalcemia. In our patient, the standard treatment was not
      enough to normalize calcemia and, in order to prevent secondary effects,
      etidronate therapy was initiated and it successfully normalized calcium levels.
      When SCFN is diagnosed, it is important to detect early hypercalcemia and treat
      it aggressively. This case provides further evidence of etidronate as an
      alternative and effective treatment for moderate-severe hypercalcemia. 

PMID- 24872128
TI  - Reply to 'William A Silverman lecture'.

PMID- 24872129
TI  - Aqueous chemistry and antiproliferative activity of a pyrone-based
      phosphoramidate Ru(arene) anticancer agent.
AB  - A water-stable phosphoramidate Ru(arene) metallodrug shows antiproliferative
      activity comparable to KP1019 in human cancer cell lines. This novel compound can
      cross-link the peptide backbone of cytochrome c, but features low apoptosis
      inducing properties. 

PMID- 24872131
TI  - Increase in CD4 count among new enrollees in HIV care in the modern
      antiretroviral therapy era.
AB  - BACKGROUND: Earlier HIV diagnosis and engagement in care improve outcomes and is
      cost effective, as a result, in 2006, the Centers for Disease Control and
      Prevention (CDC) revised the HIV-screening guidelines. We sought to determine
      whether the CD4 count (CD4) at presentation, a surrogate for time to
      presentation, increased during the study period. Our a priori hypothesis was that
      the CD4 at presentation increased during the study period, particularly after the
      CDC guideline revision. METHODS: We performed a retrospective cohort study and
      analyzed data from the HIV Research Network, a consortium of 18 US clinics caring
      for HIV-infected patients. HIV-infected adults (>=18 years old) newly presenting
      for care between 2003 and 2011 were included in this study. Multivariable linear
      regression examined associations with CD4 at enrollment. Calendar year was
      modeled as a linear spline with a change in slope at 2008, allowing determination
      of the mean change in CD4 per year during 2003-2007 and 2008-2011. RESULTS: Over
      13,543 newly presenting subjects enrolled from 2003 to 2011. Median CD4 at
      enrollment rose from 285 to 317 cells per cubic millimeter between 2003-2007 and
      2008-2011 (P < 0.001). After adjusting for age, race/ethnicity, gender, HIV risk
      factor, and clinic site, the mean increase in the CD4 count at presentation per
      year was 13.3 cells per cubic millimeter per year (95% confidence interval 6.4 to
      20.1 cells per cubic millimeter per year) greater during 2008-2011 than during
      2003-2007. CONCLUSIONS: We demonstrate a small, but statistically significant,
      increase in CD4 at presentation after the CDC guideline revision. More efforts
      are needed to decrease time to presentation to HIV care.

PMID- 24872134
TI  - Low raltegravir concentration in cerebrospinal fluid in patients with ABCG2
      genetic variants.
AB  - Adenosine triphosphate-binding cassette transporter G2 (ABCG2) is expressed on
      the cerebrospinal fluid (CSF) side of choroid plexus epithelial cells, which form
      the blood-CSF barrier. Raltegravir was recently identified as a substrate of
      ABCG2. In the present study, we analyzed the relationship between single
      nucleotide polymorphisms of ABCB1 and ABCG2 genes and raltegravir concentrations
      in 31 plasma and 14 CSF samples of HIV-infected patients treated with raltegravir
      containing regimens. The mean CSF raltegravir concentration was significantly
      lower in CA (25.5 ng/mL) and AA (<10 ng/mL) genotypes at position 421 in ABCG2
      gene compared with CC (103.6 ng/mL) genotype holders (P = 0.016).

PMID- 24872133
TI  - Exposure to entry inhibitors alters HIV infectiousness and sensitivity to broadly
      neutralizing monoclonal antibodies.
AB  - BACKGROUND: The development of envelope-specific neutralizing antibodies that can
      interfere with viral entry into target cells is important for the development of
      an HIV-1 vaccine. Another means of blocking viral entry is through the use of
      entry inhibitors such as the CCR5 inhibitor maraviroc (MVC), which can also repel
      cell-free virus particles from the cell surface. For this reason, we hypothesized
      that exposure to entry inhibitors might alter viral infectiousness and
      sensitivity to antibody-mediated neutralization. METHODS: The CCR5-tropic HIV-1
      variants BaL, AD8, and CC 1/85 were used to infect PM-1 cells in the presence of
      2 entry inhibitors, enfuvirtide and MVC. After 4 hours, culture fluids were
      ultrafiltered and the infectiousness and susceptibility to broadly neutralizing
      antibodies (2F5, 4E10, 2G12, b12, VRC01, PG9) of viruses exposed to these entry
      inhibitors were assessed using TZM-bl cells. RESULTS: Viruses exposed to the
      entry inhibitor MVC exhibited lower infectiousness than controls. Enfuvirtide
      exposure increased AD8 sensitivity to 2F5, 4E10, VRC01, and b12 and increased BaL
      sensitivity to 4E10 while lowering BaL sensitivity to b12 and VRC01. MVC-exposed
      BaL became less susceptible to the gp120-specific antibodies b12, 2G12, and
      VRC01. CONCLUSIONS: Exposure to entry inhibitors altered HIV-1 infectiousness and
      sensitivity to gp120-specific neutralizing antibodies. This alteration of entry
      inhibitor-exposed virus has implications for the development of future entry
      inhibitors and for vaccine development.

PMID- 24872130
TI  - Evaluation of rapid progressors in HIV infection as an extreme phenotype.
AB  - DESIGN: Rapid CD4 cell loss represents an HIV phenotype used to identify causal
      variants of accelerated disease progression. The optimal rate and threshold for
      identifying this extreme phenotype in recently infected individuals is unclear.
      METHODS: Using a cohort of patients with known dates of HIV-1 seroconversion
      (SC), CASCADE (Concerted Action on SeroConversion on AIDS and Death in Europe),
      we identified proportions experiencing nadir CD4 cell levels within 1 year of SC,
      and assessed their mean AIDS-free survival time at 10-year follow-up and hazard
      of AIDS/death, compared with those whose CD4 remained >500 cells per cubic
      millimeter. Follow-up was censored at December 31, 1996 to avoid bias due to
      combination antiretroviral therapy initiation. RESULTS: Of 4876 individuals,
      2.8%, 7.3%, and 24.9% experienced >=1 CD4 <100, 200, and 350 cells per cubic
      millimeter, respectively, within 1 year of SC. Minimum CD4 levels of 30, 166,
      231, and 506 cells per cubic millimeter were experienced during this period by
      1%, 5%, 10%, and 50% of individuals, respectively. Mean (95% confidence interval)
      AIDS-free survival at 10 years follow-up was 2.9 (2.3 to 3.6), 5.5 (5.0 to 6.1),
      6.7 (6.5 to 7.0), 7.4 (7.2 to 7.6), and 8.1 (7.9 to 8.3), for those with minimum
      counts <=100, 100-200, 200-350, 350-500, >500 cells per cubic millimeter,
      respectively. Using counts of >500 cells per cubic millimeter as reference, the
      hazard ratios (95% confidence interval) of AIDS/death were 15.0 (11.9 to 18.9),
      3.6 (2.9 to 4.5), 2.1 (1.8 to 2.4), and 1.5 (1.3 to 1.7), respectively. The
      hazard ratio increased to 37.5 (26.5 to 53.1) when a minimum CD4 count <100 was
      confirmed within 1 year of SC. CONCLUSION: At least 1 CD4 <=100 cells per cubic
      millimeter within the first year of SC identifies a rare group of individuals at
      high risk of disease progression and could form the basis for defining the rapid
      progressor phenotype.

PMID- 24872135
TI  - Malaria may influence the transmission of Kaposi sarcoma associated herpesvirus
      in endemic areas.

PMID- 24872132
TI  - Weight as predictors of clinical progression and treatment failure: results from
      the TREAT Asia Pediatric HIV Observational Database.
AB  - OBJECTIVE: To evaluate the value of time-updated weight and height in predicting
      clinical progression, and immunological and virological failure in children
      receiving combination antiretroviral therapy (cART). METHODS: We used Cox
      regression to analyze data of a cohort of Asian children. RESULTS: A total of
      2608 children were included; median age at cART was 5.7 years. Time-updated
      weight for age z score < -3 was associated with mortality (P < 0.001) independent
      of CD4% and < -2 was associated with immunological failure (P <= 0.03)
      independent of age at cART. CONCLUSIONS: Weight monitoring provides useful data
      to inform clinical management of children on cART in resource-limited settings.

PMID- 24872136
TI  - Tenofovir alafenamide vs. tenofovir disoproxil fumarate in single tablet regimens
      for initial HIV-1 therapy: a randomized phase 2 study.
AB  - OBJECTIVES: To evaluate the safety and efficacy of the novel tenofovir prodrug,
      tenofovir alafenamide (TAF), as part of a single-tablet regimen (STR) for the
      initial treatment of HIV-1 infection. DESIGN: Phase 2, randomized, double-blind,
      double-dummy, multicenter, active-controlled study. METHODS: Antiretroviral naive
      adults with HIV-1 RNA >=5000 copies per milliliter and a CD4 count >=50 cells per
      microliter were randomized 2:1 to receive an STR of
      elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) or
      elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF),
      plus placebo for 48 weeks. RESULTS: Patients on both E/C/F/TAF (n = 112) and
      E/C/F/TDF (n = 58) had high rates of virologic suppression (<50 HIV copies per
      milliliter) at week 24 (86.6%; 89.7%) and at week 48 (88.4%; 87.9%), and had
      similar improvements in CD4 at week 48 (177; 204), respectively. Both treatments
      were well tolerated, and most adverse events were self-limiting and of mild to
      moderate severity. Compared with patients on E/C/F/TDF, patients on E/C/F/TAF had
      smaller reductions in estimated creatinine clearance (-5.5 vs. -10.1 mL/min, P =
      0.041), significantly less renal tubular proteinuria, and smaller changes in bone
      mineral density for hip (-0.62% vs. -2.39%, P < 0.001) and spine (-1.00% vs. 
      3.37%, P < 0.001). Patients on E/C/F/TAF had higher increases in total
      cholesterol, low-density lipoprotein, and high-density lipoprotein, but the total
      cholesterol/high-density lipoprotein ratio was unchanged for both. CONCLUSIONS:
      Treatment-naive patients given the STR that contained either TAF or TDF achieved
      a high rate of virologic success. Compared with those receiving TDF, patients on
      E/C/F/TAF experienced significantly smaller changes in estimated creatinine
      clearance, renal tubular proteinuria, and bone mineral density.

PMID- 24872138
TI  - Adherence in the treatment of patients with extensively drug-resistant
      tuberculosis and HIV in South Africa: a prospective cohort study.
AB  - OBJECTIVE: Extensively drug-resistant tuberculosis (XDR-TB)/HIV coinfection is
      difficult to treat with frequent adverse drug reactions and associated with high
      mortality. Adherence to antiretroviral therapy (ARV) and second-line TB
      medications may reduce mortality, prevent amplification of drug resistance, and
      improve outcomes. METHODS: Prospective cohort study of XDR-TB patients on
      treatment in KwaZulu-Natal, South Africa. Adherence to ARV and TB medications was
      assessed separately at baseline and monthly. Knowledge, attitudes, and beliefs
      were assessed at baseline. Optimal adherence was defined as self-report of taking
      all pills in the previous 7 days; missing any pills was defined as suboptimal
      adherence. Primary outcome was optimal adherence 6 months after initiation of XDR
      TB treatment to TB medications, ARV, and both ("dual adherence"). RESULTS: One
      hundred four XDR-TB patients (79.8% HIV coinfected, 84.3% on ARV at enrollment)
      were enrolled and followed monthly (median 8 visits; interquartile range: 4-12).
      Six-month optimal adherence was higher for ARV (88.2%) than TB medications
      (67.7%) (P < 0.001). Low educational attainment, male gender, and year of
      enrollment were independently associated with dual suboptimal adherence. At
      baseline, participants indicated that XDR-TB was curable (76.0%), HIV and TB were
      linked (81.7%), and ARV improves TB outcomes (72.1%). Baseline knowledge,
      attitudes, and beliefs did not predict subsequent adherence. CONCLUSIONS:
      Medication adherence was significantly higher for ARV than for TB medications in
      this cohort. Short-course treatment regimens for drug-resistant TB with lower
      pill burden may increase adherence and improve outcomes in XDR-TB/HIV.
      Programmatic support for dual adherence is critical in the treatment of drug
      resistant TB and HIV.

PMID- 24872139
TI  - Impact and programmatic implications of routine viral load monitoring in
      Swaziland.
AB  - OBJECTIVE: To assess the programmatic quality (coverage of testing, counseling,
      and retesting), cost, and outcomes (viral suppression, treatment decisions) of
      routine viral load (VL) monitoring in Swaziland. DESIGN: Retrospective cohort
      study of patients undergoing routine VL monitoring in Swaziland (October 1, 2012
      to March 31, 2013). RESULTS: Of 5563 patients eligible for routine VL testing
      monitoring in the period of study, an estimated 4767 patients (86%) underwent
      testing that year. Of 288 patients with detectable VL, 210 (73%) underwent
      enhanced adherence counseling and 202 (70%) had a follow-up VL within 6 months.
      Testing coverage was slightly lower in children, but coverage of retesting was
      similar between and age groups and sexes. Of those with a follow-up test, 126
      (62%) showed viral suppression. The remaining 78 patients had World Health
      Organization-defined virologic failure; 41 (53%) were referred by the doctor for
      more adherence counseling, and 13 (15%) were changed to second-line therapy,
      equating to an estimated rate of 1.2 switches per 100 patient-years. Twenty-four
      patients (32%) were transferred out, lost to follow-up, or not reviewed by
      doctor. The "fully loaded" cost of VL monitoring was $35 per patient-year.
      CONCLUSIONS: Achieving good quality VL monitoring is feasible and affordable in
      resource-limited settings, although close supervision is needed to ensure good
      coverage of testing and counseling. The low rate of switch to second-line therapy
      in patients with World Health Organization-defined virologic failure seems to
      reflect clinician suspicion of ongoing adherence problems. In our study, the main
      impact of routine VL monitoring was reinforcing adherence rather than increasing
      use of second-line therapy.

PMID- 24872137
TI  - The Montreal cognitive assessment to screen for cognitive impairment in HIV
      patients older than 60 years.
AB  - Progress in HIV treatments has led to HIV-infected patients living into their 60s
      and older. Because HIV-associated neurocognitive disorder (HAND) in older age is
      associated with more executive dysfunction, cognitive screening instruments
      tapping this domain may be optimal. We examined the Montreal Cognitive Assessment
      to identify HAND in 67 HIV-infected patients older than 60 years, of which 40%
      were diagnosed with HAND. Receiver operating characteristic curve identified an
      optimal cutpoint of <= 25 for HAND with a sensitivity of 72% and specificity of
      67%. We conclude that the Montreal Cognitive Assessment has only moderate
      performance characteristics for cognitive screening of HIV-infected elders.

PMID- 24872141
TI  - Use of inhaled iloprost for the management of postoperative pulmonary
      hypertension in congenital heart surgery patients: review of a transition
      protocol.
AB  - Inhaled nitric oxide (iNO) is considered standard therapy for pediatric
      postcardiac surgical pulmonary hypertension (PH). Limited data suggest that
      inhaled iloprost (inIlo), an aerosolized prostacyclin, may be a feasible and more
      affordable therapeutic alternative. The goal of this study was to determine if
      significant hemodynamic change or adverse events would occur in postoperative
      congenital heart surgery (CHS) patients with PH after their transition from iNO
      to inIlo. This retrospective review investigated CHS patients with postoperative
      PH (mean pulmonary artery pressure [mPAP] >25 mmHg) between January 1, 2010 and
      December 31, 2011 who transitioned from iNO to inIlo. By protocol, CHS patients
      receiving stable doses of iNO were gradually transitioned to inIlo. After full
      transition, the patients received inIlo every 2 h, with a final dosing range of
      1.25-5 MUg/dose. Both PAP and systemic arterial pressure (SAP) were invasively
      measured during the transition period. Seven patients ages 10 days to 1.5 years
      completed the protocol. Measurements of mPAP (p = 0.27) and systolic PAP (p =
      0.25) did not differ between iNO and inIlo therapy alone. No serious adverse
      events or complications (bleeding or thrombocytopenia) occurred. The ratio of
      systolic PAP to SAP decreased in all patients receiving inIlo alone (p = 0.03).
      Pulmonary hypertension in postoperative CHS patients can be managed successfully
      with inIlo, and the measured hemodynamics with this agent are similar to those
      observed with iNO. For the management of postoperative PH, inIlo may be a
      reasonable alternative, thus reducing the need for costly iNO. Larger
      confirmatory studies would more robustly facilitate its integration into standard
      care.

PMID- 24872142
TI  - Anti-annexin 5 in patients with systemic lupus erythematosus.

PMID- 24872143
TI  - Mortality analysis on wastewater exposure in Shijiazhuang, Hebei, China, from
      2007 to 2011.
AB  - The study investigated the age-adjusted mortality rate and disease odds among
      deceased residents living in areas exposed to wastewater and cleanwater from 2007
      to 2011, in Shijiazhuang, China. Mortality data for eight villages exposed to
      wastewater and 16 villages not exposed to wastewater were collected and
      crosschecked from multiple sources. Overall mean age-adjusted mortality rate for
      wastewater areas was 798/105 (95% Confidence Interval (CI) = +/- 68),
      insignificantly higher than the mean mortality rate for cleanwater area, 726/105
      (95% CI = +/- 46), p > 0.05. Malignant neoplasms and respiratory mortality and
      disease odds were higher in wastewater areas than in cleanwater areas, OR = 1.7
      (95% CI = 1.3-2.2, p < 0.01) and OR = 1.9 (95% CI = 1.1-3.4, p < 0.05),
      respectively. Wastewater area mortality and disease odds for Lung and Stomach
      cancers after adjustments were OR = 1.6 (95% CI = 1.1-2.4, p < 0.05) and OR = 1.8
      (95% CI = 1.2-2.7, p < 0.01), respectively, significantly higher than those of
      cleanwater areas. There is a possibility that exposure to wastewater might be
      associated with cancer and respiratory disease mortality. The study recommends
      that the use of wastewater be limited, discouraged, or discontinued.

PMID- 24872144
TI  - Microfluidics for electronic paper-like displays.
AB  - Displays are ubiquitous in modern life, and there is a growing need to develop
      active, full color, video-rate reflective displays that perform well in high
      light conditions. The core of display technology is to generate or manipulate
      light in the visible wavelength. Colored fluids or fluids with particles can be
      used to tune the light intensity (greyscale) or wavelength (colors) of reflective
      displays by different actuation methods. Microfluidic technology plays an
      increasing role in fluidic manipulation in microscale devices used in display
      areas. In this article, we will review microfluidic technologies based on
      different actuation methods used for display applications: pressure-driven flow,
      electrophoresis, electroosmosis, electrowetting, magnetic-driven flow, and cell
      actuation principles. 

PMID- 24872145
TI  - Resveratrol attenuates bone cancer pain through the inhibition of spinal glial
      activation and CX3CR1 upregulation.
AB  - The present study examined the effects of intrathecal use of resveratrol on pain
      hypersensitivities, spinal glia activation, and CX3CR1 expression in the model of
      bone cancer pain (BCP). The BCP model was established through intrathecally
      injecting Walker 256 mammary gland carcinoma cells to Sprague-Dawley rats. We
      found that spinal CX3CR1 expression and glial activation aggravated after
      inoculation. Resveratrol (i.t.) attenuated bone cancer-induced pain
      hypersensitivities, decreased CX3CR1 expression and glial activation in the spine
      in a BCP model. Resveratrol (i.t.) also attenuated mechanical allodynia resulting
      from intrathecally injecting fractalkine in rats. Inhibition of spinal glial
      activation and CX3CR1 upregulation may involve in resveratrol's analgesic
      effects. These findings demonstrated that resveratrol attenuated pain
      facilitation through inhibiting spinal glial activation and CX3CR1 upregulation
      in a BCP model. 

PMID- 24872149
TI  - VAC therapy to promote wound healing after surgical revascularisation for
      critical lower limb ischaemia.
AB  - Vacuum-assisted closure (VAC) therapy is a new emerging non-invasive system in
      wound care, which speeds up wound healing by causing vacuum, improving tissue
      perfusion and suctioning the exudates, and facilitating the removal of bacteria
      from the wound. The application of sub-atmospheric pressure on the lesions seems
      to alter the cytoskeleton of the cells on the wound bed, triggering a cascade of
      intracellular signals that increase the rate of cell division and subsequent
      formation of granulation tissue. The aim of this study is to analyse the results
      of VAC therapy used as an adjuvant therapy for the treatment of foot wounds in
      patients affected by critical limb ischaemia (CLI) (Rutherford 6 class) after
      distal surgical revascularisation, to promote and accelerate the healing of
      ulcers. Twenty-nine patients (20 males, 9 females; mean age 68.4) affected by CLI
      of Rutherford 6 class, after surgical revascularisation of the lower limb,
      underwent VAC therapy in order to speed up wound healing. Complete wound healing
      was achieved in 19 patients (65.51%), in an average period of 45.4 +/- 25.6 days.
      VAC therapy is a valid aid, after surgical revascularisation, to achieve rapid
      healing of foot lesions in patients with CLI. 

PMID- 24872150
TI  - Hydrogen activation on Pt-Sn nanoalloys supported on mixed Sn-Ce oxide films.
AB  - We have studied the interaction of H2 with Pt-Sn nanoalloys supported on Sn-Ce
      mixed oxide films of different composition by means of synchrotron radiation
      photoelectron spectroscopy and resonant photoemission spectroscopy. The model
      catalysts are prepared in a three step procedure that involves (i) the
      preparation of well-ordered CeO2(111) films on Cu(111) followed by subsequent
      physical vapor deposition of (ii) metallic Sn and (iii) metallic Pt. The
      formation of mixed Sn-Ce oxide is accompanied by partial reduction of Ce(4+)
      cations to Ce(3+). Pt deposition leads to the formation of Pt-Sn nanoalloys
      accompanied by the partial re-oxidation of Ce(3+) to Ce(4+). Subsequent annealing
      promotes further Pt-Sn alloy formation at expense of the Sn content in the Sn-Ce
      mixed oxide. Adsorption of H2 on Pt-Sn/Sn-Ce-O at 150 K followed by stepwise
      annealing results in reversible reduction of Ce cations caused by spillover of
      dissociated hydrogen between 150 and 300 K. Above 500 K, annealing of Pt-Sn/Sn-Ce
      O in a hydrogen atmosphere results in irreversible reduction of Ce cations. This
      reduction is caused by the reaction of hydrogen with oxygen provided by the mixed
      oxide substrate via the reverse spillover to Pt-Sn nanoalloy. The extent of the
      hydrogen and oxygen spillover strongly depends on the amount of Sn in the Sn-Ce
      mixed-oxide. We observe an enhancement of hydrogen spillover on Pt-Sn/Sn-Ce-O at
      low Sn concentration as compared to Sn-free Pt/CeO2. Although the extent of
      hydrogen spillover on Pt-Sn/Sn-Ce-O with high Sn concentration is comparable to
      Pt/CeO2, the reverse oxygen spillover is substantially suppressed on these
      samples.

PMID- 24872151
TI  - Use of an active surveillance system by the FDA to observe patterns of quinine
      sulfate use and adverse hematologic outcomes in CMS Medicare data.
AB  - PURPOSE: In 2005, the Food and Drug Administration approved Qualaquin (quinine)
      for treatment of malaria and later ordered unapproved quinine formulations off
      the market. In 2009, labeling for Qualaquin added a warning for use for leg
      cramps, as serious hematologic reactions could occur. We examined quinine use
      trends among Medicare beneficiaries focusing on indications for use and
      associations with adverse hematologic outcomes. METHODS: Medicare beneficiaries,
      aged 65 years and older, in 2006-2012, were included in incident quinine or
      comparator, diltiazem, cohorts if 183 days prior to dispensing, they were
      enrolled in Medicare, had no dispensing of quinine, diltiazem, ticlodipine,
      clopidogrel, and sulfonamide drugs, and had no diagnoses of thrombocytopenia,
      immune thrombocytopenic purpura (ITP), thrombotic microangiopathy (TMA), or
      hemolytic-uremic syndrome (HUS). Diagnoses of malaria or leg cramps were observed
      during 183 days prior to index dispensing. Outcomes of ITP, TMA, or HUS in
      inpatient or emergency room settings were then observed during drug use. RESULTS:
      Prevalent use of quinine decreased by 99%, from 419 675 to 6036 users during 2006
      2012. Of 88 066 quinine users, 9 had diagnoses of malaria and 36 218 had leg
      cramps. Incidence rates (per 1000 person-years) for ITP were quinine 1.67 and
      diltiazem 0.40 [incidence rate ratio 4.2 (95% confidence interval 2.5, 6.5)], for
      TMA were quinine 0.23 and diltiazem 0.03 [incidence rate ratio 6.9 (95%
      confidence interval 1.3, 24.0)], and for HUS were quinine 0 and diltiazem 0.01.
      CONCLUSIONS: Use of quinine decreased substantially, although diagnoses of leg
      cramps persist. To our knowledge, this is the first demonstration of an
      association for quinine and ITP and TMA in claims data.

PMID- 24872152
TI  - Application of a functional marker for the effect of cryoprotectant agents on
      gorgonian coral (Junceella juncea and J. fragilis) sperm sacs.
AB  - BACKGROUND: The establishment of coral sperm repositories which retain good post
      rewarming viability and fertility play a vital role in species conservation.
      OBJECTIVE: This study aimed at obtaining baseline information regarding the
      effects of cryoprotectant agents (CPAs) on gorgonian coral (Junceella juncea and
      J. fragilis) sperm sacs. METHODS: The adenosine triphosphate assay was used to
      determine the energy level of the gorgonian sperm sacs as an indicator of sperm
      viability after exposure to cryoprotectants. RESULTS: The 'no observed effect
      concentrations' (NOECs) of methanol, dimethyl sulfoxide (DMSO), polypropylene
      glycol (PG), ethylene glycol (EG) and glycerol for J. juncea sperm sacs were 3 M,
      3 M, 1 M, 2 M and 1 M respectively after 20 min exposure; whilst the NOECs for J.
      fragilis oocytes were 2 M, 3 M, 1 M, 2 M and 2 M, respectively. Methanol and DMSO
      had the least impact. PG was the most toxic CPA after 10 min exposure. ATP
      content of J. juncea and J. fragilis sperm sacs did not differ significantly from
      the control with incubation times of 10-20 min with 2 M EG. However, ATP content
      dropped significantly after exposing sperm sacs to 2 M EG for 40 min with average
      values of 2.34 +/- 0.12 and 1.97 +/- 0.48 microg/ml respectively. ATP content for
      J. juncea and J. fragilis sperm sacs was significantly decreased to 1.79 +/- 0.31
      and 2.40 +/- 0.36 microg/ml after 20 min incubation in 2 M PG when compared to
      the control with 2.98 +/- 0.16 and 4.14 +/- 0.42 microg/ml respectively.
      Normalized ATP content for sperm sacs of two different gorgonian coral after
      incubation in methanol, DMSO, PG, EG and glycerol showed that J. juncea sperm
      sacs were slightly less tolerant to CPAs compared to J. fragilis sperm sacs.
      CONCLUSIONS: DMSO or methanol can be considered as efficient CPAs for gorgonian
      sperm sacs cryopreservation. The ATP luminescence assay provided sensitive and
      rapid quantification of mitochondrial activity in gorgonian coral sperm sacs. The
      study on the impact of CPA will contribute to the development of a
      cryopreservation protocol for coral sperm conservation.

PMID- 24872153
TI  - Evaluation of two distinct cryoprotectants for cryopreservation of human red
      blood cell concentrates.
AB  - BACKGROUND: Cryopreservaton of packed human red blood cells requires the use of
      cryoprotectants. OBJECTIVE: The study assessed physiological parameters of 40 RBC
      units frozen with either 40% glycerol or 6.7% HES. METHODS: After thawing, they
      were suspended in NaCl or in 6% HES. Tests of Hct, Hb, Na+ and K+ ions, ATP, 2,3
      DPG, pH and erythrocyte stability were measured 30 minutes and 24 hours after
      thawing. RESULTS: Hct was lower after thawing but did not differ significantly
      between two groups. Hb was lower after thawing, but was statistically significant
      higher in the HES group (43.8 g/unit vs 35.4 g/unit). K+ concentration increased
      after thawing and was significantly higher after 24 hours in the glycerol group
      (29.0 mEq/l vs 8.7 mEq/l). ATP concentration in the HES group was significantly
      lower (2.15 micromol/g) in comparison with the glycerol group (6.30 micromol/g)
      24 hours after thawing. 2,3-DPG levels did not differ significantly between the
      methods. Stability of RBCs frozen in glycerol were better (94.58%) than RBCs
      frozen in HES (80.75%) measured 24 hours after thawing. ATP is better protected
      in erythrocytes frozen in glycerol than in HES. CONCLUSION: Erythrocytes frozen
      with HES preserved more hemoglobin than with glycerol. Membrane permeability for
      Na+ and K+ ions was preserved better with HES. HES compared to glycerol offered
      better protection for erythrocytes.

PMID- 24872147
TI  - Pharmacokinetics and pharmacodynamics of antifungals in children: clinical
      implications.
AB  - Invasive fungal disease (IFD) remains life threatening in premature infants and
      immunocompromised children despite the recent development of new antifungal
      agents. Optimal dosing of antifungals is one of the few factors clinicians can
      control to improve outcomes of IFD. However, dosing in children cannot be
      extrapolated from adult data because IFD pathophysiology, immune response, and
      drug disposition differ from adults. We critically examined the literature on
      pharmacokinetics (PK) and pharmacodynamics (PD) of antifungal agents and
      highlight recent developments in treating pediatric IFD. To match adult exposure
      in pediatric patients, dosing adjustment is necessary for almost all antifungals.
      In young infants, the maturation of renal and metabolic functions occurs rapidly
      and can significantly influence drug exposure. Fluconazole clearance doubles from
      birth to 28 days of life and, beyond the neonatal period, agents such as
      fluconazole, voriconazole, and micafungin require higher dosing than in adults
      because of faster clearance in children. As a result, dosing recommendations are
      specific to bracketed ranges of age. PD principles of antifungals mostly rely on
      in vitro and in vivo models but very few PD studies specifically address IFD in
      children. The exposure-response relationship may differ in younger children
      compared with adults, especially in infants with invasive candidiasis who are at
      higher risk of disseminated disease and meningoencephalitis, and by extension
      severe neurodevelopmental impairment. Micafungin is the only antifungal agent for
      which a specific target of exposure was proposed based on a neonatal hematogenous
      Candida meningoencephalitis animal model. In this review, we found that pediatric
      data on drug disposition of newer triazoles and echinocandins are lacking, dosing
      of older antifungals such as fluconazole and amphotericin B products still need
      optimization in young infants, and that target PK/PD indices need to be
      clinically validated for almost all antifungals in children. A better
      understanding of age-specific PK and PD of new antifungals in infants and
      children will help improve clinical outcomes of IFD by informing dosing and
      identifying future research areas. 

PMID- 24872154
TI  - Cryopreservation of adventitious shoot tips of Paraisometrum mileense by droplet
      vitrification.
AB  - BACKGROUND: Gesneriaceae family contains numerous species endemic to China, and
      many of them are listed as endangered species. There is a need for a simple and
      efficient method for long-term conservation of these species. OBJECTIVE: The
      study aimed to establish an efficient procedure for cryopreserving Paraisometrum
      mileense, a critically endangered species endemic to Yunnan, China. METHODS:
      Effects of sucrose concentration of preculture solution, duration of sucrose
      preculture, duration of plant vitrification solution 2 (PVS2) treatment, and cold
      acclimation on regeneration of cryopreserved adventitious shoot tips (ASTs) were
      assessed. RESULTS AND CONCLUSION: Among different sucrose preculture regimes
      tested, preculture with 0.3M sucrose for 24h resulted in best regeneration of
      cryopreserved ASTs. PVS2 treatment also affected regeneration considerably with
      the maximum survival of ASTs after incubation in PVS2 for 90 min at 0 degrees C.
      With the optimised parameters, the level of shoot regeneration from cryopreserved
      ASTs reached 86%. No morphological abnormalities were observed during one year's
      growth of the plantlets developing from cryopreserved ASTs. Procedure established
      in this research is a promising technique for the cryopreservation of ASTs of
      this species.

PMID- 24872155
TI  - Effects of seed cryopreservation, stratification and scarification on germination
      for five rare species of pitcher plants.
AB  - BACKGROUND: Habitat loss and over collection have caused North American pitcher
      plants to become rare, including U.S. federally endangered Sarracenia alabamensis
      and S. oreophila, and S. leucophylla, S. psittacina and S. purpurea spp. venosa,
      endangered in several states. OBJECTIVE: To develop reliable seed
      cryopreservation protocols for endangered Sarracenia species enabling similar
      germination percentages before and after storage in liquid nitrogen (LN) either
      in vivo or using in vitro tools. METHODS: Seed germination pre- and post
      cryopreservation were compared following seed drying with germination in soil,
      aseptic environment with wet filter paper or enriched medium, and using
      scarification or stratification for dormancy removal. RESULTS: After cryostorage,
      germination in vitro (1/6- or 1/3-strength MS medium) increased compared to
      germination on peat moss. Germination pre- and post-cryopreservation was similar
      for S. alabamensis and S. oreophila when seeds were stratified and grown in
      vitro. S. leucophylla and S. psittacina also showed high germination after
      cryopreservation when germinated on medium following stratification. CONCLUSION:
      Rapid liquid nitrogen exposure and rewarming induced seed coat cracking that
      damaged seeds, likely allowing internal damage during acid scarification and
      microbial entry during germination in non-sterile environments.

PMID- 24872156
TI  - Effect of shooting medium and source of material on grapevine (Vitis vinifera L.)
      shoot tip recovery after cryopreservation.
AB  - BACKGROUND: Selecting experimental material at the optimal physiological stage is
      of paramount importance for successful cryopreservation. OBJECTIVE: The study was
      to investigate the effect of the physiological state of grapevine buds on their
      regrowth after liquid nitrogen exposure. METHODS: In a first set of experiments,
      we tested the regrowth of cryopreserved buds sampled from microcuttings cultured
      on shooting medium containing benzylaminopurine or zeatin riboside for various
      durations. In a second set of experiments, we studied the regrowth after liquid
      nitrogen exposure of buds sampled from different positions on the stem of in
      vitro plantlets. RESULTS: Regrowth of cryopreserved buds sampled from
      microcuttings was higher (30%), compared to buds sampled directly from in vitro
      plantlets (23%), for all culture durations of microcuttings on shooting medium
      tested (2-6 weeks). Addition of cytokinin in the shooting medium improved
      regrowth of cryopreserved buds compared to buds sampled from microcuttings
      cultured on medium devoid of growth regulators; however similar results were
      obtained with the two cytokinins tested. Buds sampled on nodes 3-4 and 6-7 (from
      the top of the stem) displayed higher regrowth compared to shoot tips. No
      significant differences were noted in regrowth after cryopreservation between
      buds sampled from microcuttings produced from the terminal node, or nodes 3-4 and
      6-7. CONCLUSION: The physiological state of the plant material is important for
      cryopreservation success. Actively growing buds sampled from microcuttings
      displayed higher regrowth compared to buds sampled directly on in vitro
      plantlets.

PMID- 24872157
TI  - Nuclear status and DNA fragmentation of oocytes from porcine, bovine and feline
      ovaries stored at 4 degrees C for 5 days.
AB  - BACKGROUND: The cooling of mammalian oocytes to sub-physiological temperatures is
      widely known to affect their viability through the induction of various
      abnormalities at all stages of meiosis. OBJECTIVE: This study was to compare the
      kinetics of nuclear status and oocyte damage in porcine, bovine and feline
      ovaries stored at 4 degrees C for 5 days. METHODS: The nuclear status and oocyte
      quality during storage were evaluated before and after maturation culture.
      RESULTS: The cold storage of ovaries decreased the proportions of porcine and
      bovine oocytes that remained at the germinal vesicle stage before maturation
      culture. The maturation rates of oocytes decreased with increasing storage time,
      independent of species. None of the porcine oocytes reached metaphase II (MII)
      after 1 day of storage. In contrast, bovine and feline oocytes from ovaries that
      were stored for 2 days and 3 days reached MII. DNA fragmentation in porcine
      oocytes from ovaries stored for 1 day was significantly higher than that in
      bovine and feline oocytes. CONCLUSION: The maturation competency of oocytes after
      the cold storage of ovaries could be related to the meiotic resumption of oocytes
      during storage and the occurrence of DNA fragmentation in oocytes during
      maturation culture.

PMID- 24872158
TI  - Cold pretreatment amplifies the responses of in vitro Eucalyptus grandis shoots
      to cryopreparative drying.
AB  - BACKGROUND: Eucalyptus grandis is an important commercial forestry species in
      South Africa. Little is known about its response (which is both drought and cold
      sensitive) to cold exposure and subsequent drying. OBJECTIVE: The study was to
      investigate the responses of E. grandis in vitro shoots to cold pretreatment.
      METHODS: E. grandis in vitro shoots were subjected to cold pretreatment (5, 10
      and 15 degrees C at different exposure periods of 1 or 3 days), different drying
      times (20, 40, 60 and 80 min over activated silica gel), and the combination of
      the selected cold pretreatment regime and subsequent drying. RESULTS: Cold
      pretreatment alone did not cause detrimental effects but elicited the
      accumulation of phenolic acids. Shoots exposed to 5 degrees C for 3 days had
      significantly higher levels of reactive oxygen species as well. The accumulation
      of ROS and phenolic acids was also noted in unacclimated, dried shoots,
      especially after 80 min of drying. In addition, these shoots had significantly
      higher levels of total soluble sugars, lower levels of starch and elevated
      proline levels. CONCLUSION: This osmotic adjustment strategy was amplified in
      cold acclimated, dried shoots (10 degrees C, 3 days; 80 min drying), which also
      had significantly lower levels of ROS, increased levels of phenolic acid, and
      higher water content and viability.

PMID- 24872159
TI  - Controlled rate cooling of fungi using a stirling cycle freezer.
AB  - BACKGROUND: The use of a Stirling cycle freezer for cryopreservation is
      considered to have significant advantages over traditional methodologies
      including N2 free operation, application of low cooling rates, reduction of
      sample contamination risks and control of ice nucleation. OBJECTIVE: The study
      assesses the suitability of an 'N2-free' Stirling Cycle controlled rate freezer
      for fungi cryopreservation. METHODS: In total, 77 fungi representing a broad
      taxonomic coverage were cooled using the N2 free cooler following a cooling rate
      of -1 degrees C min(-1). Of these, 15 strains were also cryopreserved using a
      traditional 'N2 gas chamber' controlled rate cooler and a comparison of culture
      morphology and genomic stability against non-cryopreserved starter cultures was
      undertaken. RESULTS: In total of 75 fungi survived cryopreservation, only a
      recalcitrant Basidiomycete and filamentous Chromist failed to survive. No changes
      were detected in genomic profile after preservation, suggesting that genomic
      function is not adversely compromised as a result of using 'N2 free' cooling.
      CONCLUSION: The results demonstrate the potential of 'N2-free' cooling for the
      routine cryopreservation of fungi in Biological Resource Centres.

PMID- 24872160
TI  - Screening of transgenic frost-resistant cotton using a porous silicon biosensing
      platform.
AB  - BACKGROUND: The genetic screening of exogenous gene expression is critical for
      the transgenic plant breeding. OBJECTIVE: Here, a novel label-free porous silicon
      (PSi)-based biosensor is reported for the identification of frost-resistant
      cotton. METHODS: Changes in optical response signal in the presence of antifreeze
      protein (AFP) were detected by Fourier transform infrared (FTIR)
      spectromicroscopy when binding of the target AFP protein with anti-AFP-antibodies
      was selectively captured on the PSi biosensor. RESULTS: Compared with non
      transgenic plants, significant red shifts were observed for transgenic frost
      resistant cotton lines except a transgenic line 2. CONCLUSION: The approach is
      highly efficient with lower cost and high sensitivity for detecting large number
      of transgenic samples in the trial field simultaneously. This PSi biosensing
      platform has potential commercial applications for the rapid assessment of
      transgenic plants in the field.

PMID- 24872161
TI  - Comparison of slow freezing and vitrification on ovine immature oocytes.
AB  - BACKGROUND: Immature oocytes are more sensitive to cold injury than mature
      oocytes. OBJECTIVE: The study was to evaluate the post thaw normal oocytes,
      cleavage and blastocyst rates of ovine cumulus oocyte complexes (COC's) using
      different cryoprotectants by slow freezing and Open pulled straw (OPS)
      vitrification. METHODS: In five replicates, abattoir derived COC's were collected
      and distributed into three groups. In Experiment 1, COC's were cryopreserved by a
      slow freezing protocol using 10% concentration of ethylene glycol (EG), 10%
      dimethyl sulphoxide (DMSO) or 5% EG and 5% DMSO mixture. In Experiment 2 and 3
      embryos were cryopreserved by OPS vitrification using either 33% or 40% (EG, DMSO
      or an equal mixture of EG and DMSO mixture. Normal oocytes post thaw were in
      vitro matured and parthenogenetically activated. RESULTS: Although, there was no
      difference in the number of post thaw normal oocytes between the groups, cleavage
      and blastocyst rates were higher in 10% slow freezing group than any of the
      vitrified groups. CONCLUSION: The study demonstrates better cryopreservation of
      ovine COC's by controlled slow freezing than OPS vitrification.

PMID- 24872162
TI  - Milt cryopreservation for rheophilic fish threatened by extinction in the Rio
      Grande, Brazil.
AB  - BACKGROUND: Specific protocols for milt cryopreservation have been established
      for some freshwater fish species. However, cryopreservation reduces sperm
      quality, giving unsatisfactory results in reproduction. OBJECTIVE: The objective
      of this work was to evaluate the effect of different cryoprotectants on the
      quality of Prochilodus lineatus, Brycon orbignyanus and Piaractus mesopotamicus
      milt after cryopreservation. METHODS: The milt was diluted in different
      cryoprotectant solutions containing 10% methanol, dimethyl sulfoxide, glycerol,
      propylene glycol or ethylene glycol combined with the Beltsville Thawing Solution
      extender (5%), then placed in the vapour of a liquid nitrogen (LN) storage tank
      for 24 h, after which they were immersed in LN. After rewarming, the rate (%) and
      duration (s) of milt motility and abnormal morphology were evaluated. RESULTS:
      All of cryoprotectant solutions tested used maintained the viability of P.
      lineatus and P. mesopotamicus milt. However, in P. lineatus, glycerol ensured a
      lower percentage of abnormal morphology. In case of P. mesopotamicus, all of the
      cryoprotectant solutions tested may be used in the cryopreservation process, with
      the exception of those containing glycerol. CONCLUSION: For B. orbignyanus,
      cryoprotectant solutions containing methanol and ethylene glycol are recommended
      for use in the cryopreservation process, although they reduced the quality of
      sperm post-rewarming.

PMID- 24872163
TI  - Kv4 channels underlie A-currents with highly variable inactivation time courses
      but homogeneous other gating properties in the nucleus tractus solitarii.
AB  - In the nucleus of the tractus solitarii (NTS), a large proportion of neurones
      express transient A-type potassium currents (I KA) having deep influence on the
      fidelity of the synaptic transmission of the visceral primary afferent inputs to
      second-order neurones. Up to now, the strong impact of I KA within the NTS was
      considered to result exclusively from its variation in amplitude, and its
      molecular correlate(s) remained unknown. In order to identify which Kv channels
      underlie I KA in NTS neurones, the gating properties and the pharmacology of this
      current were determined using whole cell patch clamp recordings in slices.
      Complementary information was brought by immunohistochemistry. Strikingly, two
      neurone subpopulations characterized by fast or slow inactivation time courses
      (respectively about 50 and 200 ms) were discriminated. Both characteristics
      matched those of the Kv4 channel subfamily. The other gating properties, also
      matching the Kv4 channel ones, were homogeneous through the NTS. The activation
      and inactivation occurred at membrane potentials around the threshold for
      generating action potentials, and the time course of recovery from inactivation
      was rapid. Pharmacologically, I KA in NTS neurones was found to be resistant to
      tetraethylammonium (TEA), sea anemone toxin blood-depressing substance (BDS) and
      dendrotoxin (DTX), whereas Androctonus mauretanicus mauretanicus toxin 3
      (AmmTX3), a scorpion toxin of the alpha-KTX 15 family that has been shown to
      block all the members of the Kv4 family, inhibited 80 % of I KA irrespectively of
      its inactivation time course. Finally, immunohistochemistry data suggested that,
      among the Kv4 channel subfamily, Kv4.3 is the prevalent subunit expressed in the
      NTS.

PMID- 24872165
TI  - Current Challenges in Using Patient-Reported Outcomes for Surgical Care and
      Performance Measurement: Everybody Wants to Hear From the Patient, but Are We
      Ready to Listen?

PMID- 24872166
TI  - Capillary electrophoresis based on the nucleic acid detection in the application
      of cancer diagnosis and therapy.
AB  - Cancer is malignant disease that causes many deaths worldwide every year, with
      most deaths occurring in the middle and advanced stages of cancer. Numerous
      deaths can be avoided by detecting cancer at an early stage, making early
      diagnosis and timely therapy critical for cancer treatment. Analyses at the level
      of nucleic acids rather than phenotypes can eliminate various false-positive and 
      negative results, and diagnoses can occur at an earlier stage. Many techniques
      have been developed for this purpose, including capillary electrophoresis (CE),
      which has the advantages of high-efficiency, high-speed, high-throughput,
      automation, cleanliness, and versatility, and CE can be conducted on a microscale
      or coupled with other separation techniques. These advantages afford this
      technique the ability to meet the future medical requirements that will
      undoubtedly call for amassing large numbers of samples for analysis, suggesting
      that CE may become an important tool for providing data in clinical cancer
      diagnosis and therapy. This review focuses on CE-based nucleic acid detection as
      it is applied to cancer diagnosis and therapy, and provides an introduction to
      the drawbacks and future developments of analysis with CE. 

PMID- 24872164
TI  - Testosterone-induced relaxation involves L-type and store-operated Ca2+ channels
      blockade, and PGE 2 in guinea pig airway smooth muscle.
AB  - In vascular smooth muscle, it has been described that testosterone (TES) produces
      relaxation by blocking L-type Ca(2+) channels. Recently, we found that L-type
      Ca(2+) and store-operated Ca(2+) (SOC) channels are the main membranal structures
      that provide extracellular Ca(2+) for carbachol (CCh)-induced contraction in
      airway smooth muscle (ASM). We studied the possible interactions between L-type
      and SOC channels in TES-induced relaxation in guinea pig ASM. TES (10, 32, 100,
      and 178 MUM) induced a complete relaxation of CCh-precontracted tracheal smooth
      muscle, and indomethacin partially inhibited this response. In single myocytes,
      the KCl-induced intracellular Ca(2+) increase ([Ca(2+)]i) was decreased by 32 and
      completely blocked by 100 nM TES. This androgen (32 and 100 MUM) significantly
      diminished (~25 and 49 %, respectively) the capacitative Ca(2+) entry. Myocytes
      stimulated with CCh produced a transient Ca(2+) peak followed by a sustained
      plateau. D-600 was added during the plateau phase, and a partial diminution (~35
      %) was observed. A greater decrease (~78 %) was seen when 2-aminoethyl
      diphenylborinate (2-APB, SOC antagonist) was used. The combination of both drugs
      completely abolished the Ca(2+) plateau induced by CCh. TES (100 MUM) also
      completely abolished the CCh-induced Ca(2+) plateau. Indomethacin significantly
      diminished this effect of TES. PGE2 and butaprost proportionally decreased the
      Ca(2+) plateau as indomethacin blocked it. Sarcoplasmic reticulum refilling was
      partially, dependently, and significantly diminished by TES. We concluded that
      TES-induced relaxation involves blockade of L-type Ca(2+) channels at nanomolar
      and SOC channels at micromolar concentration and PGE2 seems to be also involved
      in this phenomenon.

PMID- 24872167
TI  - Saxicola syenitica Heuglin, 1869 (Aves: Passeriformes: Muscicapidae), an
      overlooked taxon of Oenanthe?
AB  - The North African population of the Black Wheatear has been treated as Oenanthe
      leucura syenitica for over 100 years. The type of syenitica was collected by
      Heuglin in June 1852 near the southern Egypt/northern Sudan border, well outside
      the range of the sedentary Black Wheatear. Morphometric inference and genetic
      analyses of partial sequences of the mitochondrial gene COI demonstrate that the
      type specimen of syenitica is not conspecific with O. leucura, but instead is
      closely related to O. lugens of the Middle East and North Africa, being most
      similar in plumage to O. lugens warriae of the basalt deserts of north-east
      Jordan and southern Syria. While syenitica was not separable in the analysed part
      of its mitochondrial DNA from O. l. lugens and O. l. warriae, it differs in
      morphometrics and plumage features from the latter. The type specimen is a first
      summer bird with abraded plumage as expected for June, and may thus have been
      collected in its breeding range. Its morphological distinctiveness implies that
      syenitica might be taxonomically distinct from warriae. However, as it is known
      only from the type and its few associated data, we propose to treat it as a
      subspecies inquirenda of O. lugens. As a consequence of this, and the fact that
      we found no genetic or morphological differences between North African
      populations of O. leucura and riggenbachi Hartert, 1909, the name originally
      applied to the population in Western Sahara, the North African population takes
      the oldest available name to become O. leucura riggenbachi. 

PMID- 24872168
TI  - A striking new species of phytotelm-breeding tree frog (Anura: Rhacophoridae)
      from central Vietnam.
AB  - We describe a distinctive new species of phytotelm-breeding rhacophorid frog from
      central Vietnam. Gracixalus lumarius sp. nov. is distinguished from all other
      rhacophorids in Indochina by a combination of (1) medium body size (adult males
      38.9-41.6 mm; adult female 36.3 mm), (2) dorsum brown diurnally and yellow
      nocturnally, (3) venter pink, (4) tympanum and supratympanic fold indistinct (5)
      iris dark gold with a dense, relatively uniformly distributed network of black
      reticulations, (6) dorsum with distinctive white conical tubercles in males, and
      (7) eggs deposited on wall of a phyptotelm. The new species is known from montane
      bamboo and montane evergreen forest in Ngoc Linh Nature Reserve in Kon Tum
      Province, between ~1845-2160 m elevation. 

PMID- 24872169
TI  - Paedomorphosis in the scolopendrid centipede genus Asanada (Chilopoda:
      Scolopendromorpha) explains incongruence between morphological and molecular data
      sets.
AB  - The morphological characters of members of the scolopendrid genus Asanada
      Meinert, 1886 are reviewed. A number of these characters are only seen in
      embryonic or early adolescent stadia in other scolopendrids. This suggests that
      the centipedes of this genus are paedomorphic. Support for this thesis is
      provided by the very rare appearance (in only three specimens) of some otherwise
      "adult" characters. This paedomorphosis, in all probability neoteny, may account
      for the recently described incongruence between morphological and molecular data
      with respect to the position of the genus seen in cladistic analyses. 

PMID- 24872171
TI  - A new species of the genus Calotes (Squamata: Agamidae) from high elevations of
      the Knuckles massif of Sri Lanka.
AB  - A new species of agamid lizard, of the genus Calotes, is described based on
      morphological evidence. This species is restricted to the Knuckles massif (>900 m
      elevation) of Sri Lanka. The genus Calotes consists of seven species in Sri
      Lanka, five of which appear to form an endemic radiation. The new species most
      closely resembles C. liocephalus Gunther, 1872 which has an isolated population
      in the central highlands and is only known from Pundaluoya (~1000m), Dickoya
      (~1200m), Upcot (~1400m), Agrapatanas (1665m) and Peak Wilderness (Sri Pada)
      (>1400m). The populations from Pundaluoya and Dickoya appear to be locally
      extinct from the wild and are known only from museum specimens collected over 120
      years ago. Males of the new species are different from males of C. liocephalus
      because of the absence of a gular pouch; by having mid gular scales smaller in
      size than those of its counterpart; scales on the snout which are larger in size
      than those on the occipital and forehead; pectoral scales which are not enlarged;
      elongated subcaudal scales; slightly carinate and acuminate abdominal scales; and
      scales on venter which are somewhat larger in size than those on dorsum at the
      same level. Finally, we also redescribe Calotes liocephalus, and provide a key to
      the Sri Lankan species of genus Calotes. 

PMID- 24872170
TI  - A new species of striped Ichthyophis Fitzinger, 1826 (Amphibia: Gymnophiona:
      Ichthyophiidae) from Myanmar.
AB  - A new species of striped ichthyophiid caecilian, Ichthyophis multicolor sp. nov.,
      is described on the basis of morphological and molecular data from a sample of 14
      specimens from Ayeyarwady Region, Myanmar. The new species resembles
      superficially the Indian I. tricolor Annandale, 1909 in having both a pale
      lateral stripe and an adjacent dark ventrolateral stripe contrasting with a paler
      venter. It differs from I. tricolor in having many more annuli, and in many
      details of cranial osteology, and molecular data indicate that it is more closely
      related to other Southeast Asian Ichthyophis than to those of South Asia. The
      caecilian fauna of Myanmar is exceptionally poorly known but is likely to include
      chikilids as well as multiple species of Ichthyophis. 

PMID- 24872173
TI  - The larvae of Gepus invisus Navas, 1912 and Solter liber Navas, 1912, a
      comparative description (Neuroptera: Myrmeleontidae).
AB  - The third instar larvae of Gepus invisus and Solter liber are comparatively
      described and illustrated for the first time with a particular emphasis on genus
      level characters. Larval morphology confirms a close relationship between these
      genera as they differ only in minor characters. 

PMID- 24872172
TI  - Sireuma, a new genus of subterranean millipedes from the Iberian Peninsula
      (Diplopoda, Chordeumatida, Opisthocheiridae).
AB  - A new genus Sireuma is described to accommodate a new species, S. nobile, from a
      cave in Portugal. The unique features of the male gonopods and the absence of a
      postvulvar organ support the creation of a new genus. The new species is
      illustrated with scanning electron micrographs and diagrammatic drawings.
      Differences vis-a-vis its relatives are discussed, and information on the
      environment in which the new species was found is also provided. 

PMID- 24872174
TI  - A new species of Pseudopyrochroa Pic, 1906 (Coleoptera: Pyrochroidae:
      Pyrochroinae) from the Mae Chaem District, Thailand.
AB  - A new species of the fire-colored beetle genus Pseudopyrochroa Pic, 1906, is
      described from the Mae Chaem District, Chiang Mai Province, Thailand. The new
      species, Pseudopyrochroa inthanonensis sp. nov., is superficially similar to
      Pseudopyrochroa basalis (Pic), Pseudopyrochroa cardoni (Fairmaire) and
      Pseudopyrochroa fainanensis (Pic) by virtue of body color, antennal form and
      prothoracic shape. It is the second species of the genus known from Thailand, the
      other being Pseudopyrochroa diversicornis (Blair). 

PMID- 24872175
TI  - Review of the genera Hishimonus Ishihara and Litura Knight(Hemiptera:
      Cicadellidae) from the Indian subcontinent with description of new species.
AB  - This paper deals with 21 species of Hishimonus Ishihara and two species of Litura
      Knight from the Indian subcontinent. The following new species are described:
      Hishimonus acuminatus sp. nov. (India: Mizoram), H. distinctus sp. nov. (India:
      Karnataka, Kerala, Tamil Nadu. Sri Lanka), H. dwipae sp. nov. (Sri Lanka), H.
      longisetosus sp. nov. (India: Karnataka), H. spicans sp. nov. (India: Karnataka),
      H. thapai sp. nov. (Nepal), H. zeylanicus sp. nov. (Sri Lanka), and Litura
      triangula sp. nov. (India: Karnataka). Hishimonus versicolor Subba Rao &
      Ramakrishnan is removed from the genus Hishimonus and two new combinations
      namely, Hishimonus apricus (Melichar) comb. nov. (formerly in the genus Eutettix)
      and Litura tripunctatus (Li) comb. nov. (formerly in the genus Hishimonus) and a
      new name Hishimonus knightiella nom. nov. for Hishimonus apricus Knight 1970a,
      not Distant 1908 is proposed. H. gillespiei Dai, Fletcher & Zhang, H. pallidus
      Dai, Fletcher & Zhang, H. dividens Knight, H. aberrans Knight, H. concavus
      Knight, H. arcuatus Knight and Litura unda Knight are new records for India. All
      the taxa are described and new taxa are illustrated. Keys to identification of
      the species of Hishimonus and Litura found in the Indian subcontinent are also
      provided along with list of known host plants. 

PMID- 24872176
TI  - Revision of the New World genus Glyphidops Enderlein (Diptera: Neriidae) .
AB  - The genus Glyphidops Enderlein, 1922, the most widespread and speciose of the New
      World genera of Neriidae (Diptera), is revised herein. Glyphidops (Glyphidops)
      ruselatus, new species, G. (G.) steyskali, new species and G. (G.) coracinus, new
      species are described. Of the 16 previously described species, which were last
      treated by Aczel (1961), the following synonyms are proposed: Chaetomeristes
      peruanus Enderlein is treated as a junior synonym of G. (G.) bullatus
      (Enderlein); Nerius dispar Cresson, Oncopsia neutra Hennig and Oncopsia dubia
      Hennig are treated as junior synonyms of G.(O.) durus (Cresson) and Oncopsia
      seductrix Hennig, is treated as a junior synonym of G. (O.) flavifrons (Bigot).
      The species Telostylus vittatus Cresson, is removed from synonymy with G. (G.)
      filosus (Fabricius) and revalidated as senior synonym of G. ochreus Hennig. A new
      diagnosis for the genus and all species are provided, as is an identification key
      to species. New locality records are provided for Costa Rica, Colombia,
      Venezuela, Guyana, Ecuador and Brazil. 

PMID- 24872177
TI  - Revision of the subfamily Onychalginae Fain, 1988 (Acariformes: Pyroglyphidae)
      ectoparasites of passerine birds.
AB  - The subfamily Onychalginae Fain, 1988 (Acariformes: Pyroglyphidae) is a
      monophyletic lineage comprising the closest parasitic relatives of the free
      living pyroglyphid house dust mites. Onychalgine mites parasitize passerine birds
      of the families Estrildidae, Passeridae, and Ploceidae in Africa and South
      America (a single record of Onychalges spinitarsis from a piciform bird requires
      confirmation). We revise this subfamily based on external morphology of adults
      and immature stages using light and scanning electron microscopy and give a key
      to species. Onychalginae includes 2 genera: Onychalges Gaud and Mouchet, 1959 (6
      species) and Paramealia Gaud, 1968 (1 species). The genus Kivuicola Fain, 1971
      syn. nov. is synonymized with Onychalges, and its single species K. kivuana Fain,
      1971 syn. nov. is considered as a putative synonym of O. odonturus Gaud, 1968.
      Onychalges spinitarsis (Fain and Gaud, 1984) is considered as a species
      inquirenda. 

PMID- 24872178
TI  - A new green anole lizard of the "Dactyloa" clade (Squamata: Dactyloidae) from the
      Magdalena river valley of Colombia .
AB  - We describe a new species of Anolis from the Magdalena river valley in Colombia.
      The new species is morphologically similar to Anolis ibanezi and A. chocorum, but
      differs in body and dewlap color, and head scalation. We performed an exploratory
      multivariate analysis based on 15 morphological characteristics of the new
      species and A chocorum and found that differences between both species are mainly
      associated with head dimensions. A phylogenetic analysis based on morphological
      characters suggests that the new species is nested within the "Dactyloa" clade of
      Anolis. Finally, we discuss phylogenetic relationships and biogeographical
      affinities based in its distribution.  

PMID- 24872179
TI  - The Stenopsyche simplex Species Group from China with descriptions of three new
      species (Trichoptera: Stenopsychidae).
AB  - The Chinese Stenopsyche simplex Group is revised for the first time since
      Weaver's (1987) revision. The group includes 14 described species and 3 new
      species. Two diagnostic subgroups were recognized by Schmid (1959). The first
      subgroup of Chinese species includes S. anaximander Malicky 2011, S. brevata Tian
      & Zheng 1989, S. chinensis Hwang 1957, S. dentata Navas 1930, S. splendida
      Martynov 1935, S. dubia Schmid 1965, S. rotundata Schmid 1965, S. simplex Schmid
      1959, and S. tienmushanensis Hwang 1957; of these, S. dentata is assigned to this
      first subgroup for the first time. The second diagnostic subgroup includes S.
      denticulata Ulmer 1926, S. longispina Ulmer 1926, S. stoetzneri Dohler 1929, S.
      uniformis Schmid 1965 and S. formosana Kobayashi, 1987. The species newly
      described here include Stenopsyche ningshanensis sp. nov., from Shaan-xi
      Province, belonging to the first subgroup, and Stenopsyche acanthoclada sp. nov.
      and Stenopsyche jinxiuensis sp. nov., both from Guang-xi Province and belonging
      to the second subgroup. Distribution maps of the two diagnostic subgroups of
      Chinese species and illustrations of male genitalia of the three new species are
      provided along with collection data for additional specimens for the previously
      described species. 

PMID- 24872180
TI  - Description of Tingis americana nymphs (Hemiptera: Tingidae), with emphasis on
      integumentary structures.
AB  - The five instars of Tingis (Tingis) americana Drake are described and
      illustrated, with emphasis on the ontogenetic changes of integumentary
      structures. The study was performed using scanning electron microscopy. 

PMID- 24872181
TI  - Two new species and one new record of larvae of the family Johnstonianidae
      (Acari: Prostigmata) from Iran with a key to species of the genus Diplothrombium.
AB  - Diplothrombium sahragardi sp. nov. and Diplothrombium ostovani sp. nov. (Acari:
      Johnstonianidae) collected from soil samples (off host) in a forest near Asalem
      city (Iran) are described. Another species of this family Johnstoniana parva
      Wendt, Wohltmann, Eggers and Otto, 1994 is reported for the first time from Iran.
      A larva-based key to Diplothrombium is provided. 

PMID- 24872182
TI  - Digenean fauna in raptors from northeastern Argentina, with the description of a
      new species of Strigea (Digenea: Strigeidae).
AB  - The digenean fauna of six species of falconiform birds from northeastern
      Argentina is reported and a new species and several new hosts and geographical
      records are presented. Strigea proteolytica n. sp. (Strigeidae) is described from
      Buteogallus urubitinga and distinguished from their congeners by the combination
      of the following characters: plump body, conspicuous proteolytic gland, forebody
      with scarce vitelline glands, copulatory bursa with a well developed muscular
      ring (Ringnapf), and absence of true neck region in hindbody. Six previously
      known species are breifly described: Strigea falconis brasiliana Szidat, 1929
      (Strigeidae) from Milvago chimachima and Caracara plancus; Neodiplostomum
      travassosi Dubois, 1937 from Buteogallus meridionalis; Tylodelphys brevis Drago &
      Lunaschi, 2008 and Posthodiplostomum macrocotyle Dubois, 1937 (Diplostomidae)
      from Busarellus nigricollis; Spaniometra variolaris (Fuhrmann, 1904)
      (Cyclocoelidae) and Megalophallus deblocki Kostadinova, Vaucher & Gibson, 2006
      (Microphallidae) from Rostrhamus sociabilis. Literature records and information
      on distribution and host-parasite relationships is presented. 

PMID- 24872183
TI  - The fossil land and freshwater snails of Gundlkofen (Middle Miocene, Germany).
AB  - The molluscan fauna from the Middle Miocene (MN 5-6) fossil site of Gundlkofen in
      southern Germany was first reported by Gall (1980: Mitt. Bayer. Staatssaml.
      Palaont. hist. Geol., 20, 51-77). He listed 34 continental gastropod species,
      which were neither figured nor properly described in many cases. Here a revision
      of his identifications is presented, with a full description of the material and
      illustration of the best preserved specimens. Following this revision, 20 species
      are listed for Gundlkofen. Unfortunately, part of the original material was
      missing and the record of a few species could not be confirmed. The depositional
      environment seems to have been a temporary water body, like an oxbow lake,
      surrounded by a humid and warm forest and scrubland. 

PMID- 24872184
TI  - A review of the taxonomic position of Vesbius seyrigi Villiers, 1970, with a
      description of two new species of Peyrierocoris Chlond & Junkiert, 2010
      (Hemiptera: Heteroptera: Reduviidae: Harpactorinae).
AB  - Peyrierocoris seyrigi (Villiers, 1970) is redescribed and its taxonomic position
      is revised to accommodate Vesbius seyrigi Villiers, 1970, erroneously described
      under the generic name Vesbius Stal, 1865. Redescription and drawings of the
      dorsal habitus and characters of the male and female genitalia, as well as a
      drawing of the ovarian egg of P. seyrigi (Villiers, 1970), are given. Two new
      species, P. gorczycai sp. nov. and P. herczeki sp. nov., are described and
      illustrated with 21 figures. 

PMID- 24872185
TI  - First report of a complete genome sequence for a begomovirus infecting Jatropha
      gossypifolia in the Americas.
AB  - Jatropha gossypifolia is a weed that is commonly found with yellow mosaic
      symptoms growing along the roadside and in close proximity to cultivated crops in
      many farming communities in Jamaica. For the first time, the complete genome
      sequence of a new begomovirus, designated jatropha mosaic virus-[Jamaica:Spanish
      Town:2004] (JMV-[JM:ST:04]), was determined from field-infected J. gossypifolia
      in the western hemisphere. DNA-A nucleotide sequence comparisons showed closest
      identity (84 %) to two tobacco-infecting viruses from Cuba, tobacco mottle leaf
      curl virus-[Cuba:Sancti Spiritus:03] (TbMoLCV-[CU:SS:03]) and tobacco leaf curl
      Cuba virus-[Cuba:Taguasco:2005] (TbLCuCUV-[CU:Tag:05]), and two weed-infecting
      viruses from Cuba and Jamaica, Rhynchosia rugose golden mosaic virus
      [Cuba:Camaguey:171:2009] (RhRGMV- [CU:Cam:171:09]) and Wissadula golden mosaic
      St. Thomas virus-[Jamaica:Albion:2005] (WGMSTV-[JM:Alb:05]). Phylogenetic
      analysis revealed that JMV-[JM:ST:04] is most closely related to tobacco and
      tomato viruses from Cuba and WGMSTV-[JM:Alb:05], a common malvaceous-weed
      infecting virus from eastern Jamaica, and that it is distinct from begomoviruses
      infecting Jatropha species in India and Nigeria.

PMID- 24872186
TI  - Synthesis of monodisperse nanocolloidal microspheres with controlled size by
      vesicle bilayer templating.
AB  - This study describes a new method to prepare monodisperse polystyrene (PS)
      colloidal nanoparticles with controlled size ranging from 60 nm to 140 nm by the
      direct polymerization of styrene and divinylbenzene inside the bilayers of the
      polydisperse hyperbranched polymer vesicles. 

PMID- 24872187
TI  - Diverse reactions to hooking up among U.S. university students.
AB  - Hooking up is defined as a physical encounter between two people who are not
      romantically committed. This study explored whether there were subgroups of young
      adults with unique reactions to hooking up (N = 879). Psychosocial predictor
      variables (gender, depression, loneliness, intoxication level, college
      adjustment, and hope for a committed relationship) were investigated along with
      emotional reactions as the outcome variables. Through the use of cluster
      analysis, four distinct clusters were identified: Happy Hopeful, Content Realist,
      Used and Confused, and Disappointed and Disengaged. The majority (62 %) of the
      sample reported mostly positive reactions to hooking up and fell within the Happy
      Hopeful or Content Realist clusters. Protective factors in these two clusters
      included hope for a committed relationship, having realistic expectations, and
      healthy psychological adjustment. The Used and Confused and Disappointed and
      Disengaged clusters reported the most negative hooking up reactions and consisted
      of 38 % of the overall sample. These two groups reported increased depression and
      loneliness symptoms and lower levels of social adjustment as compared to those
      clusters with more positive reactions.

PMID- 24872188
TI  - An analysis of all applications for sex reassignment surgery in Sweden, 1960
      2010: prevalence, incidence, and regrets.
AB  - Incidence and prevalence of applications in Sweden for legal and surgical sex
      reassignment were examined over a 50-year period (1960-2010), including the legal
      and surgical reversal applications. A total of 767 people (289 natal females and
      478 natal males) applied for legal and surgical sex reassignment. Out of these,
      89% (252 female-to-males [FM] and 429 male-to-females [MF]) received a new legal
      gender and underwent sex reassignment surgery (SRS). A total of 25 individuals (7
      natal females and 18 natal males), equaling 3.3%, were denied a new legal gender
      and SRS. The remaining withdrew their application, were on a waiting list for
      surgery, or were granted partial treatment. The incidence of applications was
      calculated and stratified over four periods between 1972 and 2010. The incidence
      increased significantly from 0.16 to 0.42/100,000/year (FM) and from 0.23 to
      0.73/100,000/year (MF). The most pronounced increase occurred after 2000. The
      proportion of FM individuals 30 years or older at the time of application
      remained stable around 30%. In contrast, the proportion of MF individuals 30
      years or older increased from 37% in the first decade to 60% in the latter three
      decades. The point prevalence at December 2010 for individuals who applied for a
      new legal gender was for FM 1:13,120 and for MF 1:7,750. The FM:MF sex ratio
      fluctuated but was 1:1.66 for the whole study period. There were 15 (5 MF and 10
      MF) regret applications corresponding to a 2.2% regret rate for both sexes. There
      was a significant decline of regrets over the time period.

PMID- 24872189
TI  - Sexual minority women's experiences of sexual pressure: a qualitative
      investigation of recipients' and initiators' reports.
AB  - Sexual pressure can have detrimental effects to individuals both physically and
      emotionally; however, research in this area is lacking regarding the experiences
      by lesbian, gay, bisexual, queer, and questioning (LGBQ) women. This online study
      qualitatively examined sexual pressure experienced and explained by LGBQ women (n
      = 50) using grounded theory methodology. Participants responded to open-ended
      questions by providing perspectives from both those who were on the receiving end
      of the sexual pressure (recipients) and from those who pressured their partners
      (initiators). Results indicated that there were eight overarching themes, 43
      higher order categories, and 241 line-by-line codes. The eight overarching themes
      included: Reasons to Not Want Sex, Reasons for Pressuring, Reasons for Giving In,
      Actions of Initiators, Expectations, Communication, Negative Outcomes, and
      Positive Reactions. Negative Outcomes was the most common theme endorsed. Several
      higher order categories indicated the unique experiences of sexual minority
      women, namely trying to be "normal" (e.g., engaging in sexual acts as a result of
      internalized homophobia), experiencing more pressure from men, and self
      consciousness (specifically related to lack of knowledge about sex with women).
      Implications for the current study include the importance of addressing sexual
      pressure with sexual minority women and creating interventions, such as
      assertiveness training and communication skills, that could assist both
      recipients and initiators with engaging in mutually satisfactory sexual
      practices.

PMID- 24872190
TI  - A role for intrathymic B cells in the generation of natural regulatory T cells.
AB  - B cells inhabit the normal human thymus, suggesting a role in T cell selection.
      In this study, we report that B cells can modulate thymic production of CD4+
      Foxp3+ T cells (regulatory T cells [Tregs]). Mice with transgenic expression of
      BAFF (BAFF-Tg) harbor increased numbers of Helios+ Foxp3+ thymic Tregs and,
      similar to some human autoimmune conditions, also exhibit increased numbers of B
      cells colonizing the thymus. Distinct intrathymic B cell subpopulations were
      identified, namely B220+, IgM+, CD23(hi), CD21(int) cells; B220+, IgM+, CD23(lo),
      CD21(lo) cells; and a population of B220+, IgM+, CD23(lo), CD21(hi) cells.
      Anatomically, CD19+ B cells accumulated in the thymic medulla region juxtaposed
      to Foxp3+ T cells. These intrathymic B cells engender Tregs. Indeed, thymic Treg
      development was diminished in both B cell-deficient BAFF-Tg chimeras, but also B
      cell-deficient wild-type chimeras. B cell Ag capture and presentation are
      critical in vivo events for Treg development. In the absence of B cell surface
      MHC class II expression, thymic expansion of BAFF-Tg Tregs was lost. Further to
      this, expansion of Tregs did not occur in BAFF-Tg/Ig hen egg lysozyme BCR
      chimeras, demonstrating a requirement for Ag specificity. Thus, we present a
      mechanism whereby intrathymic B cells, through the provision of cognate help,
      contribute to the shaping of the Treg repertoire.

PMID- 24872191
TI  - Podocytes regulate neutrophil recruitment by glomerular endothelial cells via IL
      6-mediated crosstalk.
AB  - Stromal cells actively modulate the inflammatory process, in part by influencing
      the ability of neighboring endothelial cells to support the recruitment of
      circulating leukocytes. We hypothesized that podocytes influence the ability of
      glomerular endothelial cells (GEnCs) to recruit neutrophils during inflammation.
      To address this, human podocytes and human GEnCs were cultured on opposite sides
      of porous inserts and then treated with or without increasing concentrations of
      TNF-alpha prior to addition of neutrophils. The presence of podocytes
      significantly reduced neutrophil recruitment to GEnCs by up to 50% when cultures
      were treated with high-dose TNF-alpha (100 U/ml), when compared with GEnC
      monocultures. Importantly, this phenomenon was dependent on paracrine actions of
      soluble IL-6, predominantly released by podocytes. A similar response was absent
      when HUVECs were cocultured with podocytes, indicating a tissue-specific
      phenomenon. Suppressor of cytokine signaling 3 elicited the immunosuppressive
      actions of IL-6 in a process that disrupted the presentation of chemokines on
      GEnCs by altering the expression of the duffy Ag receptor for chemokines.
      Interestingly, suppressor of cytokine signaling 3 knockdown in GEnCs upregulated
      duffy Ag receptor for chemokines and CXCL5 expression, thereby restoring the
      neutrophil recruitment. In summary, these studies reveal that podocytes can
      negatively regulate neutrophil recruitment to inflamed GEnCs by modulating IL-6
      signaling, identifying a potential novel anti-inflammatory role of IL-6 in renal
      glomeruli. 

PMID- 24872192
TI  - Nuclear role of WASp in gene transcription is uncoupled from its ARP2/3-dependent
      cytoplasmic role in actin polymerization.
AB  - Defects in Wiskott-Aldrich Syndrome protein (WASp) underlie development of WAS,
      an X-linked immunodeficiency and autoimmunity disorder of childhood. Nucleation
      promoting factors (NPFs) of the WASp family generate F-actin in the cytosol via
      the VCA (verprolin-homology, cofilin-homology, and acidic) domain and support RNA
      polymerase II-dependent transcription in the nucleus. Whether nuclear-WASp
      requires the integration of its actin-related protein (ARP)2/3-dependent
      cytoplasmic function to reprogram gene transcription, however, remains
      unresolved. Using the model of human TH cell differentiation, we find that WASp
      has a functional nuclear localizing and nuclear exit sequences, and accordingly,
      its effects on transcription are controlled mainly at the level of its nuclear
      entry and exit via the nuclear pore. Human WASp does not use its VCA-dependent,
      ARP2/3-driven, cytoplasmic effector mechanisms to support histone H3K4
      methyltransferase activity in the nucleus of TH1-skewed cells. Accordingly, an
      isolated deficiency of nuclear-WASp is sufficient to impair the transcriptional
      reprogramming of TBX21 and IFNG promoters in TH1-skewed cells, whereas an
      isolated deficiency of cytosolic-WASp does not impair this process. In contrast,
      nuclear presence of WASp in TH2-skewed cells is small, and its loss does not
      impair transcriptional reprogramming of GATA3 and IL4 promoters. Our study
      unveils an ARP2/3:VCA-independent function of nuclear-WASp in TH1 gene activation
      that is uncoupled from its cytoplasmic role in actin polymerization. 

PMID- 24872194
TI  - High-altitude pulmonary edema: review.
AB  - OBJECTIVE: At High altitude (HA) (elevation >2,500 m), hypobaric hypoxia may lead
      to the development of symptoms associated with low oxygen pressure in many
      sojourners. High-altitude pulmonary edema (HAPE) is a potentially fatal
      condition, occurring at altitudes greater than 3,000 m and affecting rapidly
      ascending, non-acclimatized healthy individuals. It is a multifactorial disease
      involving both environmental and genetic risk factors. Since thousands of
      lowlanders travel to high altitude areas for various reasons every year, we
      thought it would be interesting to review pathological aspects related to
      hypobaric hypoxia, particularly HAPE. METHOD: Since the pathogenesis of HAPE is
      still a subject of study, we systematically identified and categorized a broad
      range of facets of HAPE such as its incidence, symptoms, physiological effects,
      pathophysiology including physiological and genetic factors, prevention and
      treatment. RESULTS: This review focuses on HA-related health problems in general
      with special reference to HAPE, which is one of the primary causes of deaths at
      extreme altitudes. Hence, it is extremely important, as it summarizes the
      literature in this area and provides an overview of this severe HA malady for
      evaluation of physiological, biochemical and genetic responses during early
      induction and acclimatization to HA. This article could be of broad scientific
      interest for researchers working in the field of high altitude medicine.

PMID- 24872195
TI  - An evaluation of the Participatory Action-Oriented Training (PAOT) program in
      small enterprises in Vietnam.
AB  - OBJECTIVES: Participatory Action-Oriented Training (PAOT) has been known as a
      practical training methodology for improving health and safety at work,
      particularly for small- and medium-sized enterprises (SMEs). Our hypothesis is
      that PAOT is a better approach than a traditional local method, and the objective
      of this study was to evaluate the efficacy of PAOT and to make suggestions for
      improvement. METHODS: An intervention was performed for one year at 20 volunteer
      SMEs. PAOT was applied in 10 factories, and a traditional local method was
      applied in the other 10 SMEs as a control. Two cross-sectional studies were
      performed consisting of a questionnaire and environmental measurements. Data were
      also collected on the number of factory improvements, productivity, worker
      income, accidents, and health costs. RESULTS: There were significant improvements
      among the intervention factories in terms of work environment, number of
      improvements and health costs between the pre- and post- intervention phases. In
      terms of productivity, significant increases were seen in the civil engineering,
      metal, garment, and rice mill industries in the intervention group, while the
      metal casting and, garment industries in the control group also showed
      significant increase in productivity. CONCLUSIONS: The findings support the idea
      that a PAOT program produces better outcomes in SMEs. It is recommended that a
      PAOT program be widely applied to SMEs to improve health and safety. A fuller
      examination could be obtained with more environmental measurements taken over a
      much longer period of time, together with data on sickness absence and accidents
      that have been independently validated.

PMID- 24872193
TI  - Tetherin promotes the innate and adaptive cell-mediated immune response against
      retrovirus infection in vivo.
AB  - Tetherin/BST-2 is a host restriction factor that could directly inhibit
      retroviral particle release by tethering nascent virions to the plasma membrane.
      However, the immunological impact of Tetherin during retrovirus infection remains
      unknown. We now show that Tetherin influences antiretroviral cell-mediated immune
      responses. In contrast to the direct antiviral effects of Tetherin, which are
      dependent on cell surface expression, the immunomodulatory effects are linked to
      the endocytosis of the molecule. Mice encoding endocytosis-competent C57BL/6
      Tetherin exhibited lower viremia and pathology at 7 d postinfection with Friend
      retrovirus (FV) compared with mice encoding endocytosis-defective NZW/LacJ
      Tetherin. Notably, antiretroviral protection correlated with stronger NK cell
      responses. In addition, Friend retrovirus infection levels were significantly
      lower in wild-type C57BL/6 mice than in Tetherin knockout mice at 2 wk
      postinfection, and antiretroviral protection correlated with stronger NK cell and
      virus-specific CD8+ T cell responses. The results demonstrate that Tetherin acts
      as a modulator of the cell-mediated immune response against retrovirus infection
      in vivo.

PMID- 24872196
TI  - Anconeus interposition arthroplasty: mid- to long-term results.
AB  - BACKGROUND: Radiocapitellar arthritis and/or proximal radioulnar impingement can
      be difficult to treat. Interposition of the anconeus muscle has been described in
      the past as an alternative option in managing arthritis, but there are little
      published data about relief of pain and restoration of function over the long
      term in patients treated with this approach. QUESTIONS/PURPOSES: We sought (1) to
      determine whether interposition of the anconeus muscle in the radiocapitellar
      and/or proximal radioulnar joint relieves pain and restores elbow function; and
      (2) to identify complications and reoperations after anconeus interposition
      arthroplasty. METHODS: Between 1992 and 2012, we surgically treated 39 patients
      having radiocapitellar arthritis and/or proximal radioulnar impingement with an
      anconeus interposition arthroplasty. These were performed for situations in which
      capitellar and/or radial head pathology was deemed not amenable to implant
      replacement. We had complete followup on 29 of them (74%) at a minimum of 1 year
      (mean, 10 years; range, 1-20 years). These 29 patients (21 males, eight females)
      had interposition of the anconeus muscle at the radiocapitellar joint (10
      elbows), the proximal radioulnar joint (two elbows), or both (17 elbows). Their
      mean age at the time of surgery was 39 years (range, 14-58 years). The reasons
      for the previous determination or the indications included lateral-side elbow
      symptoms after radial head resection (eight elbows), failed internal fixation of
      radial head fracture (two elbows), failed radial head replacement with or without
      capitellar replacement (four elbows), osteoarthritis and Essex-Lopresti injury
      (six elbows), failed internal fixation of distal humeral fracture involving the
      capitellum (two elbows), posttraumatic osteoarthritis involving the lateral
      compartment (one elbow), lateral compartment osteoarthritis associated with
      chondropathies (three elbows), and primary osteoarthritis affecting the lateral
      compartment (three elbows). Patient-reported outcome tools included the quick
      Disabilities of the Arm, Shoulder and Hand (quick-DASH) and the Mayo Elbow
      Performance Score (MEPS); we also performed a chart review for complications and
      reoperations. RESULTS: During the followup duration, the mean MEPS was
      significantly improved from (mean +/- SD) 64 +/- 17 points before surgery to 82
      +/- 14 points after surgery (p < 0.001) with 21 elbows (72%) graded as excellent
      or good at most recent followup. The mean quick-DASH score was 24 +/- 17 points
      (n = 25) at latest evaluation. Two patients (7%) had perioperative complications,
      including wound dehiscence (one elbow) and transient posterior interosseous nerve
      palsy (one elbow). Seven patients (24%) underwent additional surgery.
      CONCLUSIONS: Anconeus arthroplasty provides a reasonable surgical alternative in
      the armamentarium of procedures to address pathology at the radiocapitellar
      and/or proximal radioulnar joint. This procedure is especially attractive when
      other alternatives such as radial head replacement may be problematic secondary
      to capitellar erosion or marked proximal radius bone loss. LEVEL OF EVIDENCE:
      Level IV, therapeutic study. See Guidelines for Authors for a complete
      description of levels of evidence.

PMID- 24872197
TI  - High-energy versus low-energy extracorporeal shock wave therapy for calcifying
      tendinitis of the shoulder: which is superior? A meta-analysis.
AB  - BACKGROUND: There are several treatment options for calcifying tendinitis of the
      shoulder. The next step treatment after conservative treatment fails is still a
      matter of dispute. Extracorporeal shock wave therapy (ESWT) has been shown to be
      a good alternative to surgery, but the best treatment intensity remains unknown.
      High-energy ESWT is much more painful, more expensive, and usually is done in an
      inpatient setting, whereas low-energy ESWT can be performed in an outpatient
      setting by a physical therapist. QUESTIONS/PURPOSES: A systematic review and meta
      analysis of randomized trials was performed to answer two clear research
      questions: (1) Is there a greater increase in the Constant-Murley score in
      patients treated with high-energy ESWT compared with those treated with low
      energy ESWT by 3 months and by 6 months? (2) Is there a greater chance of
      complete resorption of the calcifications in patients treated with high-energy
      ESWT compared with those treated with low-energy ESWT by 3 months and by 6
      months? METHODS: Five relevant electronic online databases, Medline (through
      PubMed), EMBASE (through OVID), Cinahl (through EBSCO), Web of Science, and the
      Cochrane Central Register of Controlled Trials, were systematically searched. We
      also crosschecked the reference lists of articles and reviews for possible
      relevant studies. Eligible for inclusion were all randomized controlled trials
      (RCTs) that compared high-energy ESWT (> 0.28 mJ/mm(2)) with low-energy ESWT (<
      0.08 mJ/mm(2)). One author examined titles and abstracts of each identified study
      to assess study eligibility. Two reviewers independently extracted data and
      assessed the risk of bias and study quality. The primary outcome measure, the
      Constant-Murley score, was assessed by comparing mean functional outcome scores
      between the groups. Secondary outcomes were assessed using odds ratios, when
      appropriate data were pooled. Based on this process, five RCTs (359 participants)
      were included. RESULTS: All five RCTs showed greater improvement in functional
      outcome (Constant-Murley score) in patients treated with high-energy ESWT
      compared with patients treated with low-energy ESWT at 3 and 6 months. The 3
      month mean difference was 9.88 (95% CI, 9.04-10.72, p < 0.001; 6-month data could
      not be pooled). Furthermore, high-energy ESWT more often resulted in complete
      resorption of the deposits at 3 months. The corresponding odds ratio was 3.40
      (95% CI, 1.35-8.58) and p = 0.009 (6-month data could not be pooled). CONCLUSION:
      When shock wave therapy is chosen, high-energy shock wave therapy is more likely
      to result in improved Constant-Murley score and resorption of the deposits
      compared with low-energy therapy. LEVEL OF EVIDENCE: Level I, therapeutic study.
      See the Instructions for Authors for a complete description of levels of
      evidence.

PMID- 24872198
TI  - CORR Insights((r)): Paley's multiplier method does not accurately predict adult
      height in children with bone sarcoma.

PMID- 24872199
TI  - IGF-I slightly improves nuclear maturation and cleavage rate of bovine oocytes
      exposed to acute heat shock in vitro.
AB  - An in vitro model of embryo production was used to examine the effects of insulin
      like growth factor (IGF)-I on maturation and developmental competence of oocytes
      exposed to heat shock. Cumulus-oocyte complexes were matured at 38.5 degrees C or
      exposed to acute heat shock (HS; 41.5 degrees C), with or without 100 ng/ml IGF
      I, for 22 h through in vitro maturation. The experimental groups were control
      (C), C + IGF-I, HS, and HS + IGF-I. Oocytes were fertilized at the end of
      maturation, and the proportion of cleaved embryos was recorded 44 h later. HS
      during maturation increased the proportion of TUNEL-positive oocytes (P < 0.05).
      HS did not have any effect on cortical granule translocation but impaired
      resumption of meiosis, expressed as a decreased proportion of oocytes with nuclei
      in metaphase I (P < 0.05) and metaphase II (MII; P < 0.05). HS decreased the
      proportion of oocytes that cleaved (P < 0.05), in particular those oocytes that
      further developed to 4-cell-stage embryos (P < 0.05). IGF-I alleviated, to some
      extent, the deleterious effects of HS on the oocytes as reflected by a reduced
      proportion of TUNEL-positive oocytes (P < 0.03). While not significant, IGF-I
      tended to increase the proportion of MII-stage oocytes (P < 0.08) and 4-cell
      stage cleaved embryos (P < 0.06). Further examination is required to explore
      whether IGF-I also affects the developmental competence of oocytes exposed to HS.

PMID- 24872200
TI  - Facile synthesis of novel 3D nanoflower-like Cu(x)O/multilayer graphene
      composites for room temperature NO(x) gas sensor application.
AB  - 3D nanoflower-like CuxO/multilayer graphene composites (CuMGCs) have been
      successfully synthesized as a new type of room temperature NOx gas sensor.
      Firstly, the expanded graphite (EG) was activated by KOH and many moderate
      functional groups were generated; secondly, Cu(CH3COO)2 and CTAB underwent full
      infusion into the interlayers of activated EG (aEG) by means of a vacuum-assisted
      technique and then reacted with the functional groups of aEG accompanied by the
      exfoliation of aEG via reflux. Eventually, the 3D nanoflower consisting of 5-9 nm
      CuxO nanoparticles homogeneously grow in situ on aEG. The KOH activation of EG
      plays a key role in the uniform formation of CuMGCs. When being used as gas
      sensors for detection of NOx, the CuMGCs achieved a higher response at room
      temperature than that of the corresponding CuxO. In detail, the CuMGCs show a
      higher NOx gas sensing performance with low detection limit of 97 ppb, high gas
      response of 95.1% and short response time of 9.6 s to 97.0 ppm NOx at room
      temperature. Meanwhile, the CuMGC sensor presents a favorable linearity, good
      selectivity and stability. The enhancement of the sensing response is mainly
      attributed to the improved conductivity of the CuMGCs. A series of Mott-Schottky
      and EIS measurements demonstrated that the CuMGCs have much higher donor
      densities than CuxO and can easily capture and migrate electrons from the
      conduction band, resulting in the enhancement of electrical conductivity. 

PMID- 24872201
TI  - Localization and electron-electron interactions in few-layer epitaxial graphene.
AB  - This paper presents a study of the quantum corrections caused by electron
      electron interactions and localization to the conductivity in few-layer epitaxial
      graphene, in which the carriers responsible for transport are massive. The
      results demonstrate that the diffusive model, which can generally provide good
      insights into the magnetotransport of two-dimensional systems in conventional
      semiconductor structures, is applicable to few-layer epitaxial graphene when the
      unique properties of graphene on the substrate, such as intervalley scattering,
      are taken into account. It is suggested that magnetic-field-dependent electron
      electron interactions and Kondo physics are required for obtaining a thorough
      understanding of magnetotransport in few-layer epitaxial graphene.

PMID- 24872204
TI  - Visualization and communication of pharmacometric models with berkeley madonna.
AB  - Population or other pharmacometric models are a useful means to describe,
      succinctly, the relationships between drug administration, exposure
      (concentration), and downstream changes in pharmacodynamic (PD) biomarkers and
      clinical endpoints, including the mixed effects of patient factors and random
      interpatient variation (fixed and random effects). However, showing a set of
      covariate equations to a drug development team is perhaps not the best way to get
      a message across. Visualization of the consequences of the knowledge encapsulated
      within the model is the key component. Yet in many instances, it can take hours,
      perhaps days, to collect ideas from teams, write scripts, and run simulations
      before presenting the results-by which time they have moved on. How much better,
      then, to seize the moment and work interactively to decide on a course of action,
      guided by the model. We exemplify here the visualization of pharmacometric models
      using the Berkeley Madonna software with a particular focus on interactive
      sessions. The examples are provided as Supplementary Material. 

PMID- 24872203
TI  - Health status profiles in community-dwelling elderly using self-reported health
      indicators: a latent class analysis.
AB  - PURPOSE: Latent class analysis (LCA), a statistical method for identifying latent
      classes within a population using multiple indicators, has been used to study the
      heterogeneity of health among the elderly. We aim to identify health status
      profiles of older adults using LCA and examine the socio-demographic
      characteristics associated with each profile. METHODS: A community health survey
      of residents >=60 years was conducted in Marine Parade, Singapore. We performed
      LCA on seven health indicators (number of chronic conditions, activities of daily
      living (ADL) dependency, pain, depression, cognition, social isolation, and
      frequency of socialising) to identify distinct classes of health status profiles.
      Multivariable logistic regression was conducted to examine the socio-demographic
      characteristics associated with each profile. RESULTS: Of the 2,444 elderly
      interviewed, we identified two health status profiles: "Health at risk" (n = 465,
      19.0 %), and "Relatively healthy" (n = 1,979, 81.0 %). The "Health at risk"
      profile was characterised by high probabilities of 3+ chronic conditions (lambda
      = 0.63), at least one basic/instrumental ADL dependency (lambda = 0.56),
      moderate/extreme pain (lambda = 0.55), cognitive impairment (lambda = 0.29),
      depressive symptoms (lambda = 0.29), social isolation (lambda = 0.27), and
      infrequent socialisation (lambda = 0.61). Individuals who were older (65-74, 75
      84, and 85+ years), females, of non-Chinese ethnicity (Indian, Malay, and
      Others), had primary and lower education, and were unemployed/not employed were
      more likely to be "Health at risk". CONCLUSION: Using LCA, we identified two
      distinct health status profiles which accounted for the heterogeneity of the
      elderly population. Selected socio-demographic characteristics were associated
      with different profiles and provide implications for the structuring of future
      public health interventions targeting the older population.

PMID- 24872202
TI  - Normal motor adaptation in cervical dystonia: a fundamental cerebellar
      computation is intact.
AB  - The potential role of the cerebellum in the pathophysiology of dystonia has
      become a focus of recent research. However, direct evidence for a cerebellar
      contribution in humans with dystonia is difficult to obtain. We examined motor
      adaptation, a test of cerebellar function, in 20 subjects with primary cervical
      dystonia and an equal number of aged matched controls. Adaptation to both
      visuomotor (distorting visual feedback by 30 degrees ) and forcefield (applying a
      velocity-dependent force) conditions were tested. Our hypothesis was that
      cerebellar abnormalities observed in dystonia research would translate into
      deficits of cerebellar adaptation. We also examined the relationship between
      adaptation and dystonic head tremor as many primary tremor models implicate the
      cerebellothalamocortical network which is specifically tested by this motor
      paradigm. Rates of adaptation (learning) in cervical dystonia were identical to
      healthy controls in both visuomotor and forcefield tasks. Furthermore, the
      ability to adapt was not clearly related to clinical features of dystonic head
      tremor. We have shown that a key motor control function of the cerebellum is
      intact in the most common form of primary dystonia. These results have important
      implications for current anatomical models of the pathophysiology of dystonia. It
      is important to attempt to progress from general statements that implicate the
      cerebellum to a more specific evidence-based model. The role of the cerebellum in
      this enigmatic disease perhaps remains to be proven. 

PMID- 24872205
TI  - Synthesis of very small diameter silica nanofibers using sound waves.
AB  - Silica nanofibers of an average diameter ~30 nm and length ~100 MUm have been
      synthesized using an unprecedented strategy: sound waves. A new phenomenon,
      spinning off the nanofibers at silica rod tips, is also observed. 

PMID- 24872206
TI  - Epithelial mesenchymal transition in the progression of renal disease in dogs.
AB  - Chronic kidney disease (CKD) in dogs is the final common pathway resulting from
      persistent renal injury and is characterized by progressive tubulointerstitial
      damage (TID). Pathogenesis of CKD is divided into an initial inflammatory phase
      with a predominantly mononuclear infiltrate followed by a fibrotic phase with
      increased numbers of fibroblasts and extracellular matrix deposition that causes
      a progressive reduction of functional parenchyma. Proteinuria is a common
      manifestation of renal diseases in dogs, and its role in the pathogenesis of CKD
      is still uncertain. Nevertheless, the degree of proteinuria in dogs correlates
      with TID progression. Increased protein filtration may have direct effects on
      tubular epithelial cells (TECs) that induce them to express the major
      histocompatibility complex type II, and thereby contribute to lymphocyte
      recruitment. Thus, an active pro-inflammatory role is proposed for TECs in TID
      progression. Moreover TECs are believed to actively participate in the mechanisms
      of renal fibrosis. Epithelial-Mesenchymal-Transition (EMT) of TECs in canine TID
      has been studied in the last decade. Down-regulation of adhesion molecules and
      loss of epithelial markers in TECs directly correlate with the severity of TID
      and with de novo expression of mesenchymal markers. Tubular basement membrane
      (TBM) disruption is an early EMT event. Increased activity of Matrix
      Metalloproteinase-2 and its co-localization with TBM splitting suggests an active
      role for the enzyme in inducing EMT. Processes occurring in canine CKD share many
      similarities with its human counterpart, making the dog a good model in which to
      examine the mechanisms of TID progression.

PMID- 24872207
TI  - A novel SWCNT platform bearing DOTA and beta-cyclodextrin units. "One shot"
      multidecoration under microwave irradiation.
AB  - The functionalization of single-walled carbon nanotubes (SWCNTs) via microwave
      assisted grafting reactions enables efficient multidecoration in a single step. A
      novel water-soluble SWCNT platform was prepared via the simple 1,3-dipolar
      cycloaddition of azomethine ylides under dielectric heating. Thanks to a single
      grafting reaction the CNT surface binds in a 1 : 1 ratio an amino acidic beta
      cyclodextrin (beta-CD) derivative and the DOTAMA moiety (1,4,7,10
      tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid monoamide). This novel "one
      shot" synthesis, compared with multistep functionalizations, preserves the
      SWCNT's structural integrity (TEM images). Besides thermogravimetric analyses,
      the determination of the amount of beta-CD and DOTA moieties grafting onto the
      SWCNT's surface was performed on the basis of phenolphthalein and gadolinium
      complexation, respectively. 

PMID- 24872208
TI  - Bifunctional lanthanum phosphate substrates as novel adsorbents and biocatalyst
      supports for perchlorate removal.
AB  - Porous lanthanum phosphate substrates, obtained by an environmentally benign
      colloidal forming process employing methyl cellulose, are reported here as
      excellent adsorbents of perchlorate with >98% efficiency and with 100%
      reusability. Additionally, the effectiveness of such substrates as biocatalyst
      supports that facilitate biofilm formation of perchlorate reducing microbes
      (Serratia marcescens NIIST 5) is also demonstrated for the first time. The
      adsorption of perchlorate ions is attributed to the pore structure of lanthanum
      phosphate substrate and the microbial attachment is primarily ascribed to its
      intrinsic hydrophobic property. Lanthanum phosphate thus emerges as a dual
      functional material that possesses an integrated adsorption/bioremediation
      property for the effective removal of ClO4(-) which is an increasingly important
      environmental contaminant. 

PMID- 24872209
TI  - Plasma concentrations of tadalafil in children with pulmonary arterial
      hypertension.
AB  - BACKGROUND: There is no report documenting the plasma concentrations of tadalafil
      in children. This study was performed to evaluate the variability in the
      pharmacokinetics of tadalafil in children with pulmonary arterial hypertension
      (PAH) treated routinely with the drug. METHODS: Plasma samples were taken twice
      (post- and predose) after repetitive oral administration, and the pharmacokinetic
      parameters (CL/F and V/F) in individual patients were estimated by the Bayesian
      method using the nonlinear mixed effects model. We also determined the unbound
      concentration of tadalafil using ultrafiltration. RESULTS: Tadalafil was
      administered to 23 children aged between 0.25 and 17.4 years, with a mean age of
      3.58 years. The mean (+/-SD) daily dose of tadalafil was 0.97 +/- 0.41 mg/kg.
      Sixteen of the 23 children received bosentan concomitantly. The mean CL/F and V/F
      values of tadalafil were 0.149 L.h-1.kg-1 and 1.87 L/kg, respectively, which were
      higher than those reported in adults. No effects of age, bosentan, or the
      estimated glomerular filtration rate were observed on the CL/F value, indicating
      that other residual factors might account for the interindividual variability
      among children with PAH. The unbound tadalafil concentrations of the postdose
      samples ranged from 5.9 to 146 (46.9 +/- 37.1) nmol/L, higher than the reported
      IC50 value of this phosphodiesterase-5 drug for humans (2-4 nmol/L, corresponding
      to 0.8-1.6 ng/mL). CONCLUSIONS: We demonstrated variability in the total and
      unbound plasma concentrations of tadalafil in children. However, all children
      received the empirical doses of the drug; a mean dose of 0.97 mg.kg-1.d-1 showed
      sufficient unbound concentrations needed for half-maximal inhibition of human
      phosphodiesterase-5 in vitro. These observations may provide information for the
      proper use of tadalafil to treat children with PAH.

PMID- 24872210
TI  - Efficient hydrolytic cleavage of plasmid DNA by chloro-cobalt(II) complexes based
      on sterically hindered pyridyl tripod tetraamine ligands: synthesis, crystal
      structure and DNA cleavage.
AB  - Four new cobalt(ii) complexes [Co(6-MeTPA)Cl]ClO4/PF6 (2/2a), [Co(6
      Me2TPA)Cl]ClO4/PF6 (3/3a), [Co(BPQA)Cl]ClO4/PF6 (4/4a) and [Co(BQPA)Cl]ClO4/PF6
      (5/5a) as well as [Co(TPA)Cl]ClO4 (1) where TPA = tris(2-pyridylmethyl)amine, 6
      MeTPA = ((6-methyl-2-pyridyl)methyl)bis(2-pyridylmethyl)amine, 6-Me2TPA = bis(6
      methyl-2-pyridyl)methyl)-(2-pyridylmethyl)amine, BPQA = bis(2-pyridylmethyl)-(2
      quinolylmethyl)-amine and BQPA = bis(2-quinolylmethyl)-(2-pyridylmethyl)amine
      were synthesized and structurally characterized. Single crystal X-ray
      crystallography confirmed the distorted trigonal bipyramidal geometries of
      complexes 2a-5a. Spectrophotometric titrations and conductivity measurements of
      the complexes in the CH3CN-H2O mixture showed that the chloro complexes exist in
      equilibrium with the corresponding hydrolyzed aqua species, [Co(L)(H2O)](2+). The
      pKa values of the coordinated H2O in aqua complexes vary from 8.4 to 8.7 (37 
      degrees C). The interactions of the complexes (1-5) with DNA have been
      investigated at pH = 7.0 and 9.0 (10 mM Tris-HCl buffer) and 37  degrees C where
      very high catalytic cleavage was observed. Under pseudo Michaelis-Menten kinetic
      conditions, the catalytic rate constants, kcat, decrease in the order 4>2>5>1>3.
      At pH 7.0 (10 mM Tris-HCl buffer) and 37  degrees C, the kcat value for complex 4
      (6.02 h(-1)), where [Co(BPQA)(H2O)](2+) is the major species, corresponds to 170
      million rate enhancement over the non-catalyzed DNA. Electrophoretic experiments
      conducted in the presence and absence of radical scavengers (DMSO, KI, NaN3)
      ruled out the oxidative mechanistic pathway of the reaction and suggested that
      the hydrolytic mechanism is the preferred one. This finding was in agreement with
      the observed increase in the kcat values at pH 9.0 compared to the corresponding
      values at pH 7.0 as a result of the increased concentration of the reactive
      hydroxo species, [Co(L)(OH)](+). The reactivity of the synthesized complexes in
      catalyzing the DNA cleavage is discussed in relation to the steric effect imposed
      by the coordinated pyridyl ligand around the central cobalt(ii) center. 

PMID- 24872211
TI  - Higher diagnostic yield with the combined sensory index in mild carpal tunnel
      syndrome.
AB  - OBJECTIVES: The combined sensory index (CSI), a sensitive composite score of 3
      median sensory comparison studies, may still be underutilized in diagnosing mild
      cases of carpal tunnel syndrome (CTS). Our goal was to compare the effectiveness
      of the "standard" median digit 2 (D2) sensory study to a CSI algorithm in
      diagnosing mild CTS. METHODS: We retrospectively identified patients with typical
      CTS symptoms and signs. Electrodiagnostically normal patients and those having
      mild CTS diagnosed by D2 or CSI algorithm were separated into groups. RESULTS:
      Seventy-four patients were included, and 51 (68.9%) were diagnosed with mild CTS.
      Of the 51, 31 (60.8%) were diagnosed using the CSI algorithm, and 20 (39.2%) were
      diagnosed using D2 (P < 0.001). CONCLUSIONS: Our data suggest that the CSI
      algorithm is significantly more effective than the D2 to diagnose mild CTS. If
      mild CTS is diagnosed earlier, treatment can be initiated sooner and morbidity
      can likely prevented.

PMID- 24872212
TI  - Acute small fiber neuropathy following Mycoplasma infection: a rare variant of
      Guillain-Barre syndrome.
AB  - Guillain-Barre syndrome (GBS) is a well-described condition involving the
      peripheral nervous system. The most well-known form of this disease is acute
      inflammatory demyelinating polyradiculoneuropathy. Among the different variants
      of GBS described in the literature, the sensory variant is scantily recognized.
      There has been a recent attempt to classify the sensory variants of the GBS and
      bring more objectivity to this diagnostic paradigm. We report a rare sensory
      variant of GBS presenting with isolated small nerve fiber involvement
      peripherally in the limbs and associated facial nerve palsy in a patient who had
      clinical and serological evidence of a preceding Mycoplasma pneumoniae infection.
      The symptoms resolved gradually with intravenous immunoglobulin therapy. This
      case adds to the growing literature of the rare form of acute small fiber
      neuropathy and GBS variants. 

PMID- 24872213
TI  - Sixty six-month follow-up of muscle power and respiratory function in a case with
      adult-type Pompe disease treated with enzyme replacement therapy.
AB  - We report a patient with adult-type Pompe disease treated with enzyme replacement
      therapy (ERT) for 5.5 years. We evaluated pulmonary function and muscle strength
      using 6-minute walk test, manual muscle test, and dynamometer-based measurement.
      The long-term ERT resulted in a substantial improvement in the pulmonary function
      and a possible stabilization followed by mild deterioration in muscle power
      measured by dynamometer and 6-minute walk test. Our data may rationalize the long
      term use of ERT for adult-type Pompe disease in terms of maintaining pulmonary
      function. 

PMID- 24872214
TI  - Clinically amyopathic dermatomyositis: analysis of a monocentric cohort.
AB  - OBJECTIVE: Clinically amyopathic dermatomyositis (CADM) is characterized by the
      presence of specific cutaneous manifestations of dermatomyositis (DM) without
      clinical signs of muscular involvement. The aim of this study was to examine the
      prevalence, clinical characteristics, and outcome of patients with CADM followed
      at our Rheumatology Unit. METHODS: Clinical charts of patients diagnosed as DM
      were retrospectively examined. Epidemiological, clinical, laboratory,
      instrumental, and histological features of the patients at the time of diagnosis
      were collected. CADM was diagnosed in the presence of DM-like rash without
      muscular involvement. RESULTS: A total of 103 DM patients were identified, of
      these, 8 were diagnosed with CADM. Six of patients with CADM had subclinical
      muscle involvement, and were therefore classifiable as hypomyopathic DM.
      CONCLUSIONS: In our case series, CADM represents 7.7% of the total DM. However,
      if investigated with instrumental methods, most patients with CADM result to have
      subclinical muscular involvement.

PMID- 24872215
TI  - Peripheral neuropathy after hair dye exposure: a case report.
AB  - We present a case of length-dependent sensory axonal polyneuropathy due to lead
      exposure from a cosmetic product. Serial follow-ups showed a direct relationship
      between the lead level, clinical symptoms, and the polyneuropathy. Our patient
      had a relatively short-term exposure to lead after misusing a hair dye on his
      beard. Nerve conduction studies showed a predominantly axonal sensory neuropathy
      that correlated with lead blood levels and reached 3 times the upper limit of
      normal. The patient had an unexpected sensory predominant neuropathy. He had a
      full recovery after stopping the lead-containing product. Blood lead levels were
      noted to be below previously reported toxic levels. No other systemic signs of
      lead toxicity were noted. This could be related to the mucosal route of
      absorption inducing a reversible injury at lower than previously reported lead
      levels and after a shorter duration of exposure. 

PMID- 24872216
TI  - Kennedy disease with biphasic clinical course and rapid progression.
AB  - We report a case of spinal and bulbar muscular atrophy (SBMA), also known as
      Kennedy disease, with a 38 CAG-repeat expansion in exon-1 of the androgen
      receptor gene, presenting with a 2-year history of mild speech difficulty,
      dysphonia, and occasional choking. Initial clinical features and complementary
      studies were consistent with SBMA. The disease progression, as assessed by the
      Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised, remained stable
      over the first 5 years from the onset but showed a rapid decline (from 42 to 24
      points) over the next 18 months before his death. In the later stages of the
      disease, deep tendon reflexes were preserved in limbs and a brisk jaw-jerk reflex
      and bilateral Hoffmann sign were evident. Survival from disease onset was 78
      months. The final cause of death was aspiration pneumonia. The atypical clinical
      features, evolution, and accelerated disease course are not concordant with the
      relatively short 38 CAG-repeat expansion in the androgen receptor gene. This may
      represent either a variant SBMA phenotype, which has not been recorded to date,
      or the development of amyotrophic lateral sclerosis in a known case of SBMA. 

PMID- 24872217
TI  - Treatment-refractory myasthenia gravis.
AB  - Myasthenia gravis (MG) is the most common disorder of neuromuscular transmission
      and is a prototypical autoimmune disorder. Most patients with MG are successfully
      treated with acetylcholinesterase inhibitors, corticosteroids, and/or steroid
      sparing agents such as azathioprine and mycophenolate mofetil. There is a small
      subset of patients, however, with treatment-refractory disease. In these cases,
      medications such as rituximab, high-dose cyclophosphamide, and eculizumab may be
      used. Thymectomy (in some cases repeat thymectomy) is another option in selected
      patients. Studies evaluating these and other forms of therapy in treatment
      refractory MG are reviewed. 

PMID- 24872219
TI  - Clinical improvement of monomelic amyotrophy after avoidance of sustained neck
      flexion.

PMID- 24872220
TI  - A 23-year-old man with acute onset paresthesias and gait ataxia.

PMID- 24872221
TI  - A novel exopolysaccharide from deep-sea bacterium Zunongwangia profunda SM-A87:
      low-cost fermentation, moisture retention, and antioxidant activities.
AB  - Many marine microorganisms can secrete exopolysaccharides (EPSs) which have
      important applications in biotechnology. We have purified a novel EPS from deep
      sea bacterium Zunongwangia profunda SM-A87, identified its glycosyl composition
      and linkage, and optimized its production to 8.9 g/l in previous studies. To
      reduce the fermentation cost, an economical fermentation medium containing 60.9 %
      whey, 10 g/l soybean meal, and 2.9 % NaCl was developed. The EPS yield of batch
      fermentation in this medium reached 12.1 +/- 0.3 g/l. Fed-batch fermentation was
      conducted and led to an EPS yield of 17.2 +/- 0.4 g/l, which represents the
      highest EPS yield ever reported for a marine bacterium. The EPS was extracted and
      it displayed good rheological properties, moisture-retention ability, and
      antioxidant activity. Particularly, its moisture-retention ability is superior to
      that of other marine bacterial EPSs reported to date. SM-A87 EPS also showed high
      antioxidant activity. These results suggest that SM-A87 EPS has promising
      potentials in biotechnology.

PMID- 24872222
TI  - A posteriori dietary patterns: how many patterns to retain?
AB  - Principal component analysis (PCA) and cluster analysis are used frequently to
      derive dietary patterns. Decisions on how many patterns to extract are primarily
      based on subjective criteria, whereas different solutions vary in their food
      group composition and perhaps association with disease outcome. Literature on
      reliability of dietary patterns is scarce, and previous studies validated only 1
      preselected solution. Therefore, we assessed reliability of different pattern
      solutions ranging from 2 to 6 patterns, derived from the aforementioned methods.
      A validated food frequency questionnaire was administered at baseline (1993-1997)
      to 39,678 participants in the European Prospective Investigation into Cancer and
      Nutrition-The Netherlands (EPIC-NL) cohort. Food items were grouped into 31 food
      groups for dietary pattern analysis. The cohort was randomly divided into 2
      halves, and dietary pattern solutions derived in 1 sample through PCA were
      replicated through confirmatory factor analysis in sample 2. For cluster
      analysis, cluster stability and split-half reproducibility were assessed for
      various solutions. With PCA, we found the 3-component solution to be best
      replicated, although all solutions contained >=1 poorly confirmed component. No
      quantitative criterion was in agreement with the results. Associations with
      disease outcome (coronary heart disease) differed between the component
      solutions. For all cluster solutions, stability was excellent and deviations
      between samples was negligible, indicating good reproducibility. All quantitative
      criteria identified the 2-cluster solution as optimal. Associations with disease
      outcome were comparable for different cluster solutions. In conclusion,
      reliability of obtained dietary patterns differed considerably for different
      solutions using PCA, whereas cluster analysis derived generally stable,
      reproducible clusters across different solutions. Quantitative criteria for
      determining the number of patterns to retain were valuable for cluster analysis
      but not for PCA. Associations with disease risk were influenced by the number of
      patterns that are retained, especially when using PCA. Therefore, studies on
      associations between dietary patterns and disease risk should report reasons to
      choose the number of retained patterns. 

PMID- 24872223
TI  - Dietary calcium requirements do not differ between Mexican-American boys and
      girls.
AB  - Mexican Americans are an understudied ethnic group for determinants of bone
      health, although the risk of age-related osteoporosis is high in this rapidly
      growing sector of the U.S. population. Thus, the objective of the present study
      was to establish the dietary calcium requirements for bone health in Mexican
      American adolescents by measuring calcium retention calculated from balance in
      response to a range of dietary calcium intakes and to determine predictors of
      skeletal calcium retention. Adolescents aged 12-15 y were studied twice on paired
      calcium intakes ranging from 600 to 2300 mg/d using randomized-order, crossover 3
      wk balance studies. Skeletal calcium retention was calculated as dietary calcium
      intake minus calcium excreted in feces and urine over the last 2 wk of balance. A
      linear model was developed to explain the variation in calcium retention. Boys (n
      = 20) were taller and had higher lean mass, usual dietary calcium intake, bone
      mineral content, and serum alkaline phosphatase compared with girls, whereas
      girls (n = 20) had higher Tanner scores and greater fat mass. Calcium retention
      increased with calcium intake (P < 0.0001) and did not differ by sex (P = 0.66).
      In boys and girls considered together, calcium intake explained 33% of the
      variation in calcium retention. Serum alkaline phosphatase explained an
      additional 11% of the variation in calcium retention. Other variables measured,
      including the urine N-telopeptide of type I collagen/creatinine ratio, Tanner
      score, serum parathyroid hormone and 25-hydroxyvitamin D, weight, height, and
      body mass index, did not contribute to the variance in calcium retention. In
      adolescence, calcium retention in both Mexican-American boys and girls was higher
      than determined previously in adolescent nonHispanic white girls. This trial was
      registered at clinicaltrials.gov as NCT01277185. 

PMID- 24872224
TI  - Cohort Profile: The Japanese Population-based Osteoporosis (JPOS) Cohort Study.
AB  - The Japanese Population-based Osteoporosis (JPOS) Cohort Study was launched in
      1996 to produce a reference database of areal bone mineral density (aBMD) by dual
      energy X-ray absorptiometry (DXA) and bone turnover markers in the Japanese
      female population and to determine risk factors for osteoporotic fractures. At
      baseline, 3984 women aged 15 to 79 years were randomly selected to provide
      representative bone status data and aBMD values for the diagnosis of
      osteoporosis. Follow-up surveys were conducted in 1999, 2002, 2006 and 2011/12 to
      determine changes in aBMD and identify incident morphometry-confirmed vertebral
      fractures and clinical fractures. These outcomes were obtained from 2174 women
      who participated in at least one follow-up survey. JPOS is a unique resource of
      individual-level bone health information with radiological and biological
      archives that include DXA images, and serum, plasma and DNA for future analyses
      with emerging radiological and biological techniques. The JPOS dataset is not
      freely available, but new collaborations are encouraged. Potential collaborators
      are invited to contact the Secretary General (M.I.) at the administrative office
      of the JPOS Study Group. 

PMID- 24872226
TI  - To suck or not to suck: medicinal leech therapy for lower extremity wounds in
      patients with peripheral arterial disease.

PMID- 24872225
TI  - A systematic review of stated preference studies reporting public preferences for
      healthcare priority setting.
AB  - BACKGROUND: There is current interest in incorporating weights based on public
      preferences for health and healthcare into priority-setting decisions. OBJECTIVE:
      The aim of this systematic review was to explore the extent to which public
      preferences and trade-offs for priority-setting criteria have been quantified,
      and to describe the study contexts and preference elicitation methods employed.
      METHODS: A systematic review was performed in April 2013 to identify empirical
      studies eliciting the stated preferences of the public for the provision of
      healthcare in a priority-setting context. Studies are described in terms of (i)
      the stated preference approaches used, (ii) the priority-setting levels and
      contexts, and (iii) the criteria identified as important and their relative
      importance. RESULTS: Thirty-nine studies applying 40 elicitation methods reported
      in 41 papers met the inclusion criteria. The discrete choice experiment method
      was most commonly applied (n = 18, 45.0 %), but other approaches, including
      contingent valuation and the person trade-off, were also used. Studies
      prioritised health systems (n = 4, 10.2 %),
      policies/programmes/services/interventions (n = 16, 41.0 %), or patient groups (n
      = 19, 48.7 %). Studies generally confirmed the importance of a wide range of
      process, non-health and patient-related characteristics in priority setting in
      selected contexts, alongside health outcomes. However, inconsistencies were
      observed for the relative importance of some prioritisation criteria, suggesting
      context and/or elicitation approach matter. CONCLUSIONS: Overall, findings
      suggest caution in directly incorporating public preferences as weights for
      priority setting unless the methods used to elicit the weights can be shown to be
      appropriate and robust in the priority-setting context.

PMID- 24872227
TI  - A density functional theory study of oxygen reduction reaction on non-PGM Fe-Nx-C
      electrocatalysts.
AB  - First-principles density functional theory (DFT) calculations were performed to
      explain the stability of catalytically active sites in Fe-Nx-C electrocatalysts,
      their ORR activity and ORR mechanism. The results show that the formation of
      graphitic in-plane Fe-N4 sites in a carbon matrix is energetically favorable over
      the formation of Fe-N2 sites. Chemisorption of ORR species O2, O, OH, OOH, and
      H2O and O-O bond breaking in peroxide occur on both Fe-N2 and Fe-N4 sites. In
      addition to the favorable interaction of ORR species, the computed free energy
      diagrams show that elementary ORR reaction steps on Fe-Nx sites are downhill.
      Thus, a complete ORR is predicted to occur via a single site 4e(-) mechanism on
      graphitic Fe-Nx (x = 2, 4) sites. Because of their higher stability and working
      potential for ORR, Fe-N4 sites are predicted to be prime candidate sites for ORR
      in pyrolyzed Fe-Nx-C electrocatalysts. 

PMID- 24872228
TI  - Exploring psychological responses to genetic testing for Lynch Syndrome within
      the family context.
AB  - OBJECTIVE: Genetic testing for hereditary cancer susceptibility syndromes is a
      family-centered process. Nonetheless, little research has explored how the family
      context affects psychological responses to genetic testing. We examine how
      personal test results and the test results of immediate and extended family
      members shape responses to genetic testing. METHODS: Individuals at risk of
      carrying a mutation associated with an inherited cancer susceptibility syndrome
      (Lynch syndrome) received genetic testing. Six months after receiving their
      results, participants reported on cancer distress, cancer worry, and depressive
      symptoms. RESULTS: Among mutation carriers for Lynch syndrome, the higher the
      proportion of carriers in their immediate family, the less cancer worry and
      distress they reported. In contrast, mutation carriers and non-carriers with a
      high proportion of carriers in their immediate family and mutation carriers with
      a high proportion of carriers in their extended family were at elevated risk for
      clinically significant levels of depressive symptoms. CONCLUSION: Personal test
      results alone are not highly predictive of psychological outcomes. Instead, the
      interaction between personal and family test results, or in some cases, family
      test results alone, predict key psychological outcomes. The current research has
      important implications for genetic counseling and intervention efforts. Published
      2014. This article is a U.S. Government work and is in the public domain in the
      USA.

PMID- 24872229
TI  - Effects of low-dose recombinant interleukin 2 to promote T-regulatory cells in
      alopecia areata.
AB  - IMPORTANCE: An impaired inhibitory function of circulating CD4+CD25+ regulatory T
      (Treg) cells was reported to play a key role in alopecia areata (AA). We report
      the first use to our knowledge of low-dose interleukin 2 for treating severe AA
      by promoting the recruitment of Treg cells. OBSERVATIONS: We conducted a
      prospective open pilot study in 5 patients with severe AA resistant to previous
      systemic treatments. Subcutaneous interleukin 2 (1.5 million IU/d) was
      administered during 5 days, followed by three 5-day courses of 3 million IU/d at
      weeks 3, 6, and 9. The primary outcome was the evolution of the Severity of
      Alopecia Tool (SALT) score, evaluated by 2 independent investigators on
      standardized photographs. Lesional skin biopsy specimens and peripheral blood
      lymphocyte phenotype were analyzed. The median SALT score went from 82 (range, 63
      100) at baseline to 69 (range, 28-100) at 6 months. Immunochemical analysis
      revealed the appearance or a notable increase in Treg cell count in 4 of 5
      patients at the end of the treatment compared with baseline. No serious adverse
      event was reported. CONCLUSIONS AND RELEVANCE: The partial regrowth achieved in 4
      of 5 patients and the recruitment of Treg cells in lesional skin support the
      interest of promoting Treg cells for treating AA. Further investigations are now
      required to confirm and to optimize the design in order to enhance the Treg cell
      response. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01840046.

PMID- 24872230
TI  - An AIE-active luminophore with tunable and remarkable fluorescence switching
      based on the piezo and protonation-deprotonation control.
AB  - A novel luminophore TPENSOH was facilely synthesized from the building blocks of
      tetraphenylethylene and 6-hydroxylbenzothiazole and exhibited unique AIE
      properties. This new dye was found to show a remarkable and reversible four-color
      switching based on a single molecule in the solid state. 

PMID- 24872231
TI  - Revision of the new world species of Hylurgops LeConte, 1876 with the description
      of a new genus in the Hylastini Coleoptera: Scolytinae) and comments on some
      Palearctic species.
AB  - The New World species of the genus Hylurgops LeConte are revised and Hylurgops
      subcostulatus Mannerheim is transferred to the new genus Pachysquamus. A revised
      key to the tribe Hylastini which can be used for the world fauna is presented to
      include Pachysquamus. Our studies suggest that the Nearctic species H. knausi
      Swaine is a valid taxon, distinguishable from the Mesoamerican H. planirostris
      Chapuis. The subspecies H. rugipennis rugipennis Mannerheim and H. r. pinifex
      Fitch are considered distinct species. A key to Hylurgops species of the New
      World is provided to accommodate the restituted species. Due to their broadly
      separated procoxae the Palearctic species H. bonvouloiri and H. inouyei do not
      agree with the genus Hylurgops. 

PMID- 24872232
TI  - Taxonomic, bioacoustic and faunistic data on a collection of Tettigonioidea from
      Eastern Congo (Insecta: Orthoptera).
AB  - During a 14-day excursion in March 1990, 28 species of tettigonioids were found
      at Irangi (1o54'S, 28o27'E), ca.100 km north west of Bukavu at Lake Kivu
      (Democratic Republic of the Congo, formerly Zaire), and at other localities near
      Bukavu. One species -Arantia (Arantia) gracilicercata Heller sp. n. - is new to
      science, another one-Pantecphyllus helleri Schmidt et al. 2004-was already
      described as new in a generic revision. All our specimens of the morphologically
      quite diverse and sexually dimorphic phaneropterine genus Arantia were studied
      using molecular methods. We propose a new subgenus Arantia (Euarantia) Heller
      subgen. n. based on relative tegmen width. Songs and stridulatory organs were
      studied in 9 species. Two phaneropterines, Horatosphaga leggei and Pardalota
      asymmetrica, showed remarkable calling songs lasting more than 10 s and produced
      by quite complicated stridulatory movements. The song of the large phaneropterine
      Zeuneria biramosa is noteworthy because of its unusually low carrier frequency of
      3.7 kHz. Based on the examination of other specimens and species, some taxonomic
      changes are proposed (Phaneropteridae Burmeister, 1838 stat. rev.; Afromecopoda
      monroviana (Karsch, 1886) stat. rev.; Leproscirtus ebneri Karny, 1919, syn. n.,
      Leproscirtus karschi Karny, 1919, syn. n., Leproscirtus granulosus aptera Karny,
      1919, syn. n., all synonyms of Leproscirtus granulosus (Karsch, 1886);
      Lanistoides Sjostedt, 1913 stat. rev.; Plastocorypha cabrai Griffini, 1909 stat.
      n.).

PMID- 24872233
TI  - An illustrated key to the species of subgenus Gyrostoma Kirby, 1828 (Hymenoptera,
      Vespidae, Polistinae) from China, with discovery of Polistes (Gyrostoma)
      tenuispunctia Kim, 2001.
AB  - The Chinese species of the subgenus Gyrostoma Kirby, 1828 of the polistine genus
      Polistes are reviewed. An illustrated key to the seven species of the subgenus
      known from China is given. New synonymy are proposed for Polistes rothneyi
      Cameron, 1900 =P. rothneyi grahami van der Vecht, 1968, syn. nov.; =P. r.
      hainanensis van der Vecht, 1968, syn. nov.; =P. r. iwatai van der Vecht, 1968,
      syn. nov.; =P. r. gressitti van der Vecht, 1968, syn. nov.; =P. r. tibetanus van
      der Vecht, 1968, syn. nov.; = P. r. yayeyamae Matsumura, 1908, syn. nov.; =P. r.
      koreanus van der Vecht, 1968, syn. nov.; =P. r. sikkimensis van der Vecht, 1968,
      syn. nov.. P. (Gyrostoma) tenuispuntia Kim, 2001 is newly recorded from China.
      Its nest is described for the first time. Compared with the sympatric and similar
      species P. rothneyi f. grahami the nest is concealed in a hollow space instead of
      having the nest directly exposed under an eave as in P. rothneyi. The differences
      in nest architecture are briefly discussed. 

PMID- 24872234
TI  - Two new scorpion species from Paposo, in the coastal desert of Taltal, Chile
      (Scorpiones, Bothriuridae, Brachistosternus).
AB  - Brachistosternus paposo n. sp. and Brachistosternus barrigai n. sp. are described
      from Paposo, in the coastal transitional desert of northern Chile.
      Brachistosternus paposo n. sp. is closely related to Brachistosternus roigalsinai
      Ojanguren-Affilastro 2002, and B. barrigai n. sp. is closely related with
      Brachistosternus kamanchaca Ojanguren-Affilastro, Mattoni & Prendini 2007. 

PMID- 24872235
TI  - Two new species of free-living marine nematodes (Nematoda: Oncholaimida:
      Enchelidiidae) from Maemul Island, Korea.
AB  - Two new species of the family Enchelidiidae Filipjev, 1918 were collected from
      marine sediments near Maemul Island in South Korea: a new species of Abelbolla
      Huang & Zhang, 2004 and a new species of Ledovitia Filipjev, 1927. Abelbolla
      maemulensis sp. nov. is characterized by its small size (1,493 * 38 um, body
      length * maximum body diameter); the presence of a circular amphid; the
      gubernacular apophysis with swollen distal tip; and the complex structure of the
      gubernaculum. It is close to Abelbolla huanghaiensis Huang & Zhang, 2004, but
      differs by the structure of gubernacular apophysis and body length (1,493 vs
      2,303 um). Ledovitia brevis sp. nov. can be separated from its congeners by its
      small size of body, the length of gubernacular apophysis, and the length of the
      spicules. It is close to Ledovitia pharetrata Wieser, 1953a, but differs by the
      length of the body (1,699 vs 2,640 um) and the spicules (40 vs 100 um). 

PMID- 24872236
TI  - The King of the Dwarves: a new cryptic species of Dainty Frog (Anura:
      Pyxicephalidae: Cacosternum) from the eastern Great Escarpment of South Africa.
AB  - Phylogenetic reconstruction using the mitochondrial 16S marker shows the presence
      of a cryptic species of Cacosternum (Anura: Pyxicephalidae) from the eastern
      Great Escarpment of South Africa, supporting the Greater Maputaland-Pondoland
      Albany region of vertebrate endemism. Bioacoustic and morphological
      characteristics, in conjunction with colouration differences, allow the
      description of this cryptic species. Tadpoles and details of life history are
      described. 

PMID- 24872237
TI  - Replacement names and nomenclatural comments for problematic species-group names
      in Europe's Neogene freshwater Gastropoda.
AB  - Over the last 250 years of taxonomic descriptions of freshwater gastropods a
      large number of primary and secondary homonyms were produced. Several of them
      have now been uncovered in the course of a new database project. To overcome the
      associated nomenclatural problems we propose 10 replacement names: Theodoxus
      pseudodacicus nom. nov., Theodoxus stoicai nom. nov., Viviparus deleeuwi nom.
      nov., Viviparus lubenescuae nom. nov., Viviparus wesselinghi nom. nov.,
      Melanopsis anistratenkoi nom. nov., Melanopsis gearyae nom. nov., Melanopsis
      magyari nom. nov., Melanopsis vrcinensis nom. nov., and Pyrgula rusti nom. nov.
      Additionally, we discuss taxa that might become secondary homonyms because of
      uncertain genus attributions. The genera Melanoptychia Neumayr, 1880 and
      Boistelia Cossmann, 1909 are synonymized with Melanopsis Ferussac, 1807 in
      Ferussac & Ferussac, 1807 based on the lack of sufficient separation criteria.
      Involved combinations are expounded and recombined accordingly. The nomenclatural
      problems regarding Melanopsis costata Fuchs, 1870 (non Olivier, 1804) and
      Planorbis varians Fuchs, 1870 sensu Bandel (2010) are discussed. 

PMID- 24872238
TI  - A new Andean species of Philodryas (Dipsadidae, Xenodontinae) from Ecuador.
AB  - We describe a new species of Philodryas from the highlands of southern Ecuador.
      The new species is distinguished from all known species of Philodryas by a unique
      combination of coloration, scalation, and hemipenial characters. The new species
      resembles Philodryas simonsii in color pattern. However, they differ notoriously
      by their hemipenial morphology. The three other trans-Andean members of the genus
      (Philodryas simonsii, Philodryas chamissonis, and Philodryas tachymenoides),
      along with the new species, compose a probably monophyletic group that may be
      characterized by the presence of ungrooved postdiastemal teeth in the maxilla.
      Unlike most species of the genus Philodryas, the new species shows a restricted
      distribution, being apparently endemic to a small region of high-altitude (3150
      4450m) grasslands in the southern Andes of Ecuador. 

PMID- 24872240
TI  - Plectranthias alcocki, a new anthiine fish species (Perciformes: Serranidae) from
      the Arabian Sea, off southwest India.
AB  - A new species of anthiine fish, Plectranthias alcocki n. sp. is described and
      illustrated based on two specimens, (63.7-72.5 mm SL), recently collected from
      deep-waters of the Arabian Sea, off Kollam, Kerala, India. The following
      combination of characters distinguishes it from all other congeners: Dorsal-fin
      rays X, 15; anal-fin rays III, 7; pectoral-fin rays 14, all unbranched; pelvic
      fin rays I, 5; lateral-line complete, the pored lateral-line scales 28; scales
      above lateral line to origin of dorsal fin 1; scales dorsally on head extending
      to posterior nostrils; no scales on maxilla or chin; gill rakers 5 + 11 (2 + 7
      developed); circumpeduncular scales 10; fourth dorsal spine longest, 2.8 (2.6) in
      head length (HL), longest dorsal-fin soft ray (second)  2.4 (2.7) in head length;
      body depth 34.4 (35)% SL; head length 46 (49.8)% SL; orbital length 8.6 in SL;
      margin of preopercle finely serrate, the serrae 33 (28), ventral edge without
      antrorse spines; dorsal fin continuous and notched; first anal-fin spine 4.9
      (5.6) in HL, second anal-fin spine 2.2 (2.6) in HL; pelvic fins relatively short,
      4.0-4.3 in SL; the dorsal fin with a black blotch at base of fourth to eighth
      spines, one at base of the last three spines, and two at base of soft portion of
      fin, the dark pigment extending onto adjacent body. 

PMID- 24872239
TI  - Insular species swarm goes underground: two new troglobiont Cylindroiulus
      millipedes from Madeira (Diplopoda: Julidae).
AB  - Two new species of the genus Cylindroiulus Verhoeff, 1894, C. julesvernei and C.
      oromii, are described from the subterranean ecosystem of Madeira Island,
      Portugal. Species are illustrated with photographs and diagrammatic drawings. The
      new species belong to the Cylindroiulus madeirae-group, an insular species swarm
      distributed in the archipelagos of Madeira and the Canary Islands. We discuss the
      differences between the new species and their relatives and present information
      on the subterranean environment of Madeira. An updated overview of the
      subterranean biodiversity of millipedes in Macaronesia is also provided. 

PMID- 24872241
TI  - Latin abbreviations and words used in scale insect literature (Hemiptera:
      Sternorrhyncha: Coccoidea).

PMID- 24872242
TI  - Metaxonchium persicum sp. n. from Iran (Nematoda, Dorylaimida, Belondiridae),
      with an updated taxonomy of the genus.
AB  - A new species of the genus Metaxonchium is described from natural habitats in
      Iran. The new species is characterized by having body length of 2.46-3.12 mm, lip
      region offset by constriction and 8-11 um wide, odontostyle fusiform and 10-12 um
      long, neck 773-1150 um long, anterior portion of pharynx bearing a spindle-shaped
      thickening with valve-like structures inside, both parts of the pharynx separated
      by a short isthmus-like narrowing, pharyngeal expansion 531-825 um long and
      occupying up to three-fourths of total neck length, female genital system
      monodelphic-opisthodelphic, anterior genital branch reduced to a large uterine
      sac and a small terminal mass, posterior uterus long and tripartite with an
      intermediate region bearing apophyses, V = 53-57, caudal region conoid with
      broadly rounded terminus (24-35 um, c = 79-105, c' = 0.6-0.9), spicules 92-103 um
      long and 7-10 spaced ventromedian supplements, at least two of them within the
      range of spicules. The taxonomy of the genus Metaxonchium is updated, including a
      list of its species, a key to their identification and a compendium of their
      morphometrics. Four species are transferred from Axonchium to Metaxonchium: M.
      coxi, M. japonicum, M. mizukuboi and M. zealandicum. 

PMID- 24872243
TI  - A new Cyrtodactylus (Squamata: Gekkonidae) from Khanh Hoa Province, southern
      Vietnam.
AB  - We describe a new species of the genus Cyrtodactylus from southern Vietnam, based
      on morphological and molecular datasets. Cyrtodactylus cucdongensis sp. nov. is
      described on the basis of seven specimens collected from Cuc Dong Cape, Khanh Hoa
      Province. The new species can be distinguished from the remaining bent-toed
      geckos by a combination of the following characters: maximum SVL 65.9 mm; 16-19
      dorsal tubercle rows; 41-44 ventral scales at midbody; 5 or 6 precloacal pores in
      males, 4-6 pitted precloacal scales in females; no femoral pores; 6-13 enlarged
      precloacal scales; 5-9 enlarged femoral scales; no transversally enlarged
      subcaudals; dorsal pattern consisting of irregular dark bands. This is the
      33<sup>rd</sup> species of Cyrtodactylus known from Vietnam. 

PMID- 24872244
TI  - Sexual dimorphism in Tripedaliidae (Conant 1897) (Cnidaria, Cubozoa, Carybdeida).
AB  - The family Tripedaliidae was re-defined and expanded based on a molecular
      phylogenetic hypothesis by Bentlage et al. (2010, Proceedings of the Royal
      Society Biological Science, 277: 497). Additionally, Bentlage et al. (2010)
      proposed that all members of the family Tripedaliidae present dimorphism in
      gonads and have structures that function as seminal vesicles (at least in males).
      Until now, no information on Tripedalia binata concerning gonad morphology,
      sexual dimorphism, spermatophore formation or structures that serve as seminal
      vesicles or spermathecae were published. We studied mature medusae of both sexes
      of Tripedalia cystophora, Tripedalia binata and Copula sivickisi in order to
      compare these structures in their stomach regions. We found sexual dimorphism and
      spermatophore formation in seminal vesicle-like structures in all three species.
      In particular, we show that along with the females of Copula sivickisi, the
      females of Tripedalia cystophora and Tripedalia binata also possess structures
      that store spermatophores and serve as spermathecae. The results are in agreement
      with the morphological synapomorphies for Tripedaliidae outlined in Bentlage et
      al. (2010), but suggest an adjustment of the diagnosis of Tripedaliidae
      (underlined): All carybdeids that display sexual dimorphism of the gonads,
      produce spermatophores and in which males and females possess subgastral sacs,
      pockets or purses which function as seminal vesicles or spermathecae.

PMID- 24872245
TI  - Red hot chili pepper. A new Calluella stoliczka, 1872 (Lissamphibia: Anura:
      Microhylidae) from Sarawak, East Malaysia (Borneo).
AB  - A new brightly-coloured (olive and red) species of microhylid frog of the genus
      Calluella Stoliczka 1872 is described from the upper elevations of Gunung
      Penrissen and the Matang Range, Sarawak, East Malaysia (Borneo). Calluella capsa,
      new species, is diagnosable in showing the following combination of characters:
      SVL up to 36.0 mm; dorsum weakly granular; a faint dermal fold across forehead;
      toe tips obtuse; webbing on toes basal; lateral fringes on toes present; outer
      metatarsal tubercle present; and dorsum greyish-olive, with red spots; half of
      venter bright red, the rest with large white and dark areas. The new species is
      the eighth species of Calluella to be described, and the fourth known from
      Borneo. A preliminary phylogeny of Calluella and its relatives is presented, and
      the new taxon compared with congeners from Malaysia and other parts of south-east
      Asia.  

PMID- 24872246
TI  - Revision of the subgenus Persexarthrus Voss of the genus Anthonomus Germar
      (Coleoptera: Curculionidae: Anthonomini).
AB  - The subgenus Persexarthrus Voss, 1944 of the weevil genus Anthonomus Germar, 1817
      is revised. Anthonomus (Persexarthrus) behnei sp. n. is described. A neotype of
      Bradybatus ornatoides Reitter, 1898 and lectotypes for Anthonomus baudueri var.
      abeillei Desbrochers des Loges, 1892, A. cyprius Marshall, 1925 and Neobradybatus
      variabilis Hoffmann, 1963 are designated. The five species of the subgenus are
      described, keyed and their distributions given. 

PMID- 24872247
TI  - Description of Helicotylenchus persiaensis sp. n. (Nematoda: Hoplolaimidae) from
      Iran .
AB  - In order to identify the species of Helicotylenchus Steiner, 1945 present in
      Iran, 497 soil and root samples were collected from the rhizosphere of different
      plants and localities throughout the country during 2009-2010. A new and several
      known species of Helicotylenchus were identified from the collected material. H.
      persiaensis sp. n. is characterized by its short tail (8-11 um , c = 54.2-79.0,
      c' = 0.6-1.2), usually with smooth terminus or with 1-3 very coarse annules,
      rarely with minor ventral, dorsal or lateral projection, conical and truncate
      head with 4-5 distinct annules, stylet 22-26 um long with anteriorly flattened
      knobs, relatively short body length (570-730 um) and absence of males. This
      species was collected from the rhizosphere of zelkova (Zelkova carpinifolia) and
      maple (Acer sp.) forest trees in Golestan province, northern Iran. Also observed
      were H. abunaamai Siddiqi, 1972, with a small ventral projection at the tail
      terminus, and H. crenacauda Sher, 1966, with long projection and indented
      terminus, collected from sugarcane (Haft-Tapeh, Khuzestan province) and rice
      rhizosphere (Chabok-Sar, Gilan province), respectively. This is the first report
      of H. abunaamai from Iran. New data on H. crenacauda are provided. 

PMID- 24872248
TI  - A new small karst-dwelling species of Cyrtodactylus (Reptilia: Squamata:
      Gekkonidae) from Java, Indonesia.
AB  - A new small karst-dwelling species of the genus Cyrtodactylus is described from
      East Java and Special Province of Yogyakarta, Indonesia. Cyrtodactylus semiadii
      sp. nov. is a small species (SVL to 47.1 mm in females, 42.1 mm in males)
      distinguished from all other congeners by unique characters combination: short,
      robust, cylindrical tail, indistinct ventrolateral folds, absence of precloacal
      groove, absence of enlarged femoral scales, absence of precloacal and femoral
      pores and lack of enlarged median subcaudal scales. It is the third member of the
      genus recorded from Java.  

PMID- 24872250
TI  - Cell specificity and molecular mechanism of antibacterial and antitumor
      activities of carboxyl-terminal RWL-tagged antimicrobial peptides.
AB  - Antimicrobial peptides (AMPs) constitute a diverse class of naturally occurring
      or synthetic antimicrobial molecules that have potential for use in the treatment
      of drug-resistant infections. Several undesirable properties of AMPs, however,
      may ultimately hinder their development as antimicrobial agents. Thus, new
      synthetic strategies, including primarily the de novo design of AMPs, urgently
      need to be developed. In this study, a series of peptides, H-(RWL) n (n = 1, 2,
      3, 4, or 5), were designed. H represents GLRPKYS from the C-terminal sequence of
      AvBD-4. Our results showed that these RWL-tagged peptides can kill not only
      bacteria but also human hepatocellular carcinoma HepG2 cells. However, the
      peptide tagged with two repeats of RWL (GW13) showed less affinity to human
      embryonic lung fibroblast MRC-5 cells or human red blood cells (hRBCs) than HepG2
      cells. These results demonstrated that GW13, with high amphiphilicity, exerted
      great selectivity toward bacteria and cancer cells, sparing host mammalian cells.
      The mechanism of action against bacteria was elucidated through combined studies
      of scanning electron microscopy (SEM) and fluorescence assays, showing that the
      peptide possessed membrane-lytic activities against microbial cells. The
      fluorescence assays illustrated that GW13 induced apoptosis in HepG2 cells. The
      cell morphology of HepG2 cells, observed by SEM, further illustrated that GW13
      causes cell death by damaging the cell membrane. Our results indicate that GW13
      has considerable potential for future development as an antimicrobial and
      antitumor agent. 

PMID- 24872252
TI  - Erratum.

PMID- 24872251
TI  - The aqueous colloidal suspension of ultrathin 2D MCM-22P crystallites.
AB  - The action of a tetrapropylammonium hydroxide solution on lamellar zeolite
      precursor MCM-22P produced a stable aqueous colloidal suspension which was shown
      by X-ray diffraction, small angle X-ray scattering and atomic force microscopy to
      contain ultrathin two-dimensional (2D) crystallites, including one-unit cell
      thick (i.e., 2.5 nm) monolayers. 

PMID- 24872254
TI  - Nanoscale layer-selective readout of magnetization direction from a magnetic
      multilayer using a spin-torque oscillator.
AB  - Technology for detecting the magnetization direction of nanoscale magnetic
      material is crucial for realizing high-density magnetic recording devices.
      Conventionally, a magnetoresistive device is used that changes its resistivity in
      accordance with the direction of the stray field from an objective magnet.
      However, when several magnets are near such a device, the superposition of stray
      fields from all the magnets acts on the sensor, preventing selective recognition
      of their individual magnetization directions. Here we introduce a novel readout
      method for detecting the magnetization direction of a nanoscale magnet by use of
      a spin-torque oscillator (STO). The principles behind this method are dynamic
      dipolar coupling between an STO and a nanoscale magnet, and detection of
      ferromagnetic resonance (FMR) of this coupled system from the STO signal. Because
      the STO couples with a specific magnet by tuning the STO oscillation frequency to
      match its FMR frequency, this readout method can selectively determine the
      magnetization direction of the magnet.

PMID- 24872253
TI  - Impact of bilateral subthalamic stimulation on motor/cognitive functions in
      Parkinson's disease.
AB  - It is still unclear whether deep brain stimulation targeted to the bilateral
      subthalamic nucleus (STN-DBS) affects cognitive function in Parkinson's disease
      (PD). This prospective study was aimed to systemically evaluate the impact of
      bilateral STN-DBS on motor and cognitive functions in patients with PD. This
      study included totally 11 Japanese patients with medically intolerant PD.
      Neurological and cognitive status was precisely evaluated before and 1 year after
      bilateral STN-DBS, using unified Parkinson's disease rating scale (UPDRS),
      levodopa equivalent doses, mini-mental state examination (MMSE), Japanese adult
      reading test (JART), repeatable battery for the assessment of neuropsychological
      status (RBANS), and Wechsler adult intelligence scale-revised (WAIS-R).
      Preoperative RBANS and WAIS-R identified cognitive dysfunction that could not be
      detected by MMSE and JART. Before surgery, PD patients had significantly impaired
      immediate memory and attention. Motor function significantly improved 1 year
      after bilateral STN-DBS. Bilateral STN-DBS did not affect any score on cognitive
      examinations. However, postoperative improvements of total score on RBANS and
      performance intelligence quotient (PIQ) scores on WAIS-R were closely related to
      those of UPDRS part III off (R(2) = 0.61, P < 0.01; R(2) = 0.39, P < 0.05,
      respectively). These findings strongly suggest that bilateral STN-DBS may
      significantly improve cognitive function in a certain subgroup of patients whose
      therapeutic effects on motor function are prominent. 

PMID- 24872256
TI  - Rethinking the foundations of global governance for health: the youth response.

PMID- 24872255
TI  - The acute and chronic effects of different right ventricular site pacing on left
      ventricular mechanical synchrony as assessed by phase analysis of SPECT
      myocardial perfusion imaging.
AB  - BACKGROUND: This study aimed to assess acute and chronic effects of right
      ventricular mid-septum (RVS) versus right ventricular apex (RVA) pacing on left
      ventricular (LV) mechanical dyssynchrony using phase analysis of gated single
      photon emission computed tomography myocardial perfusion imaging (MPI). METHODS:
      Thirty-nine patients with complete atrioventricular (AV) block, who were
      indicated for permanent pacing, were recruited and randomized to receive RVA (n =
      20) or RVS (n = 19) pacing. All patients underwent MPI at 1 week and 6 months
      after pacemaker implantation. LV dyssynchrony and cardiac function were assessed
      by MPI and compared between the two groups. RESULTS: There were no significant
      differences in baseline characteristics between the RVS and RVA groups. The paced
      QRS duration was significantly longer in the RVA group than in the RVS group. LV
      dyssynchrony parameters were not significantly different between the groups at
      the 1-week follow-up, but they were significantly smaller in the RVS group than
      in the RVA group at the 6-month follow-up. LV dyssynchrony parameters
      significantly decreased in the RVS group from the 1-week follow-up to the 6-month
      follow-up, but were unchanged in the RVA group. No differences in LV function
      parameters were observed between the groups at the 1-week and 6-month follow-ups.
      CONCLUSIONS: RVS pacing produces better electrical and mechanical synchrony than
      RVA pacing for patients with complete AV block.

PMID- 24872258
TI  - Characteristics of postpartum pain associated with vaginal and caesarean births.
AB  - BACKGROUND: It is desirable that nursing mothers should return to normal
      activities so as to encourage early care of the newborn. This desire will be met
      if the common postpartum maternal morbidities are identified and managed
      accordingly. OBJECTIVE: To identify and characterize postpartum pain in the
      immediate postpartum period after vaginal or caesarean birth. METHODS: Women who
      delivered in our hospital; over 18 years, delivered of a live neonate and were in
      hospital for at least 2 days were studied. The socio-demographic characteristics,
      site of pain and self report of pain were recorded. The mothers were interviewed
      to describe the nature of postpartum pain using the Short-Form McGill Pain
      Questionnaire. RESULTS: A total of 116 patients participated in the study; 50/116
      were nulliparous, and 100/116 received prenatal care. The incidence of pain was
      82.8%. 55/74 women who had vaginal delivery and 41/42 post c-section women had
      pain. Only 51/96 women reported their pain and a good proportion of the women
      received some form of analgesia for the pain. Post c-section women were more
      likely to use affective descriptors than those who had vaginal delivery. The use
      of affective descriptors provoked higher VAS scores. CONCLUSION: Pain in the
      immediate postpartum period is common and more severe in women who had caesarean
      section than vaginal delivery. There is need to improve current methods of
      managing postpartum pain in the sub-region.

PMID- 24872257
TI  - Asymmetrically interacting spreading dynamics on complex layered networks.
AB  - The spread of disease through a physical-contact network and the spread of
      information about the disease on a communication network are two intimately
      related dynamical processes. We investigate the asymmetrical interplay between
      the two types of spreading dynamics, each occurring on its own layer, by focusing
      on the two fundamental quantities underlying any spreading process: epidemic
      threshold and the final infection ratio. We find that an epidemic outbreak on the
      contact layer can induce an outbreak on the communication layer, and information
      spreading can effectively raise the epidemic threshold. When structural
      correlation exists between the two layers, the information threshold remains
      unchanged but the epidemic threshold can be enhanced, making the contact layer
      more resilient to epidemic outbreak. We develop a physical theory to understand
      the intricate interplay between the two types of spreading dynamics. 

PMID- 24872259
TI  - Clinico-pathological study of female genital malignancies in Olabisi Onabanjo
      University Teaching Hospital, Sagamu, Ogun State, Nigeria.
AB  - OBJECTIVE: To ascertain the pattern and frequency of female genital malignancies
      among the different age groups, the common presenting complaints of cervical
      cancer patients and stages of presentation as seen in Sagamu, Ogun State.
      METHODOLOGY: A retrospective analysis of reports of formalin fixed paraffin
      embedded tissue blocks and slides of all female genital samples received at
      Morbid Anatomy & Histopathology Department of Olabisi Onabanjo University
      Teaching Hospital, Sagamu from January 1st, 2003 to June 30th, 2012. The personal
      data and clinical history were retrieved from laboratory forms and the patients'
      case files. RESULTS: The age range of patients whose specimens were reviewed was
      between 21-85 years. Cancers of the cervix accounted for majority (65.1%) of the
      cases followed by ovarian cancer (23.2%) and cancer involving the uterus (10.5%).
      Sixty-six percent of the cervical cancer patients are 50 years and above.
      Majority of the cervical cancer cases (82.2%) were squamous cell carcinoma. The
      common clinical features were post-menopausal bleeding (53.3%), vaginal discharge
      (43.3%), and intermenstrual bleeding (16.7%). The interval between onset of
      symptoms and seeking of healthcare was 6.7 +/- 3.66 months. Stage IIIB cervical
      cancer was seen in 40% of the cervical cancer patients analyzed while no case of
      Stage IA was seen. Ninety-three percent of these patients were referred for
      radiotherapy. CONCLUSION: Cancer of the cervix is the commonest gynaecological
      malignancy and most patients presented late. Free or government subsidized
      cervical cancer screening programmes and awareness campaign is highly
      recommended.

PMID- 24872261
TI  - Comparison of unreamed interlocking nail and external fixation in open tibia
      shaft fracture management.
AB  - BACKGROUND: The management of open tibia fractures remains controversial despite
      increase in its incidence. Some surgeons avoid internal fixations for fear of
      infection while others have demonstrated its superiority. Identifying an optimal
      management modality is of utmost benefit to our patients. Study objectives were
      to compare the rate of infection and mean duration to healing in the management
      of open tibia fractures using unreamed interlocking intramedullary nail and
      external fixation. METHODS: The study was an interventional study comparing two
      known standard methods of managing open tibia fractures conducted in the
      orthopaedic and trauma department of a tertiary health institution in South west,
      Nigeria. Forty patients who presented with open tibia fractures were allocated
      alternately into primary interlocking nailing group and external fixation group.
      Follow-up was for two years. RESULTS: Incidences of deep wound infection in both
      groups were 35% (external fixation) and 11.1% (interlocking nailing)
      respectively. The relative risk of developing infection in external fixation
      group was 3.2. Mean duration to union was 14.8 weeks and 14.4 weeks in the
      external fixation and interlocking nailing groups respectively, difference in
      mean was not statistically significant, (t=0.133, p=0.895). CONCLUSION: The risk
      of wound infection was observed to be higher in this study with the use of
      external fixation in the management of open tibia fractures compared with
      unreamed interlocking intramedullary nail.

PMID- 24872262
TI  - Comparison of effect of retrograde and antegrade approaches to interlocking nail
      fixation of femoral diaphyseal fractures on ipsilateral hip and knee joint
      motion.
AB  - PURPOSE: The objective of this study was to evaluate the early impact of
      antegrade and retrograde interlocking nail fixation of femoral diaphyseal
      fractures on the ipsilateral hip and knee joint range of motion. METHODS: A
      prospective evaluation was performed of 62 consecutive limbs with femoral
      diaphyseal fractures that had interlocking nail fixation through the antegrade or
      retrograde approaches. All participants had post-operative physiotherapy. Follow
      up was for 9 months. RESULTS: The mean maximum hip flexion angle at 9 months was
      137.50 in the antegrade group and 133.80 in the retrograde group (p = 0.150).
      Trendelenburg test was negative in both groups and there was no knee extension
      lag at 9 months. While the mean maximum knee flexion angle at 9 months was 119.90
      in the retrograde group and 134.50 in the antegrade group (p = 0.023). All
      patients had achieved radiologic and clinical fracture union by twenty four weeks
      post-operatively. CONCLUSION: There was no significant effect of antegrade or
      retrograde approach on the range of motion of the hip joint. However, knee motion
      improved more quickly in the group that had antegrade nailing.

PMID- 24872263
TI  - Evaluation of diagnostic performances of visual cervical inspection with acetic
      acid and colposcopy in Benin city, Nigeria.
AB  - OBJECTIVE: To determine the performance indicators of visual inspection with
      acetic acid (VIA) and colposcopy to detect cervical premalignant lesions.
      METHODS: A prospective cross-sectional study evaluating performance indicators of
      visual cervical inspection with acetic acid and colposcopy using directed biopsy
      for histopathology as the reference standard in a Colposcopy unit at a referral
      tertiary hospital in Nigeria. Consecutive sample of 212 apparently healthy,
      ambulant, asymptomatic women with an intact uterus and with no past history of
      cervical neoplasia were recruited. RESULTS: A total of 195 women had VIA and
      satisfactory colposcopy with directed biopsy. Overall test positivity was 29.7%
      for VIA, 36.9% for colposcopy and 32.8% for histology of colposcopically directed
      biopsy. Using CIN 2 as the disease threshold; the sensitivity, specificity,
      positive predictive value and negative predictive value of VIA were 70.8%, 67.0%,
      29.3% & 94.9% while those of colposcopy were 87.5%, 97.7%, 84.0%
      &98.2%,respectively. CONCLUSION: Although the test characteristics of both VIA
      and colposcopy appear satisfactory in this study, the data suggests that
      colposcopy performs better than VIA in the diagnosis of cervical neoplasia.
      However, in view of its ease of administration and low logistic requirements, VIA
      still has a vital role to play in population-based screening in our environment.

PMID- 24872264
TI  - Prevalence of hepatitis d infection in patients with hepatitis B virus-related
      liver diseases in Accra, Ghana.
AB  - BACKGROUND: Hepatitis D virus (HDV), a defective RNA virus which depends on
      hepatitis B virus (HBV) for its replication and expression, appears to be highly
      pathogenic and modifies the natural history of HBV infection. Two types of
      infection, co-infection and super-infection are recognised. During infection,
      anti-delta antibodies appear in serum and can be detected by Enzyme linked
      Immunosorbent Assay (ELISA). OBJECTIVE: We determined the prevalence of hepatitis
      D infection amongst HBsAg-positive patients with HBV-related liver diseases in
      Accra, Ghana using an Enzyme linked Immunosorbent assay (ELISA) method. METHODS:
      We collected blood samples from 53 patients with hepatitis B-related liver
      diseases. The sera were analysed using a commercially available kit, the EIA-ANTI
      HDV, a third generation ELISA kit (Globe Diagnostics, Italy). RESULTS: There were
      39 males (73.6%) and 14 females (26.4%) giving a male:female ratio of about
      3:1.The mean age of patients was 38.6 years (range, 15-75). Six patients were
      reactive for anti-delta antibodies, yielding a HDV sero-prevalence of 11.3%. A
      higher proportion of males were anti-HDV positive (9.4%) compared to females
      (1.9%) but the difference was not statistically significant (p=0.350). Anti-HDV
      was detected in 4(22.2%) patients with chronic hepatitis B, 1(7.6%) with
      cirrhosis of the liver and 1(5.3%) with hepatocellular carcinoma. CONCLUSION: The
      prevalence of HDV infection amongst patients with liver disease in Accra with HBV
      related liver diseases appears to be high compared to developed countries but
      similar to several developing countries. No significant difference exists in
      gender prevalences. A concerted public health effort is required to reduce this
      high prevalence rate.

PMID- 24872265
TI  - Hypoxaemia in hospitalised under-five Nigerian children with pneumonia.
AB  - BACKGROUND: Hypoxaemia constitutes a possible complication of severe respiratory
      illness which is often under-reported in developing countries. Therefore, the
      current study was carried out to determine the prevalence and clinical predictors
      of hypoxaemia in hospitalized under-five children with pneumonia in Ilorin,
      Nigeria. METHODS: This is a descriptive cross-sectional study of 200 children
      aged between two months and five years with pneumonia recruited consecutively.
      Socio-demographic, clinical and laboratory data were obtained. The pulse oximetry
      measurement was recorded after a stable reading for at least one minute while the
      child was breathing room air. Hypoxaemia was defined as an arterial oxygen
      saturation of less than 90%. Data was analyzed using the SPSS 20.0 software.
      RESULTS: The male/female ratio was 1.5:1.The prevalence of hypoxaemia in the
      children with pneumonia was 41.5%.Using a linear regression analysis, the
      clinical features that were significantly associated with hypoxaemia were
      restlessness, lower chest wall indrawing, bronchial breath sounds and tender
      hepatomegaly (p<0.05 each). Restlessness had a sensitivity of 22.9%, specificity
      of 91.5%, while chest wall indrawing had a sensitivity of 86.7% and specificity
      of 53.3%. Bronchial breath sound had a sensitivity of 16.9%, a specificity of
      95.7% whereas tender hepatomegaly had a sensitivity of 48.2% and specificity of
      82.9%. CONCLUSION: There is a high local burden of pneumonia-associated
      hypoxaemia. Restlessness, chest wall indrawing, bronchial breath sounds and
      tender hepatomegaly could be useful in detecting pneumonia-related hypoxemia in
      poorly equipped health facilities.

PMID- 24872266
TI  - Choice of medical specialties amongst final year medical students in two
      universities in South-South, Nigeria.
AB  - Study aimed at determining the preferred medical specialties among final year
      medical students and the most important factor(s) influencing their choices.
      METHODS: A cross-sectional questionnaire-based survey was carried out among all
      final year medical students from the University of Benin (UNIBEN) and the Niger
      Delta University (NDU). The study was done in UNIBEN in July 2011 and
      subsequently in NDU in March 2012.Students were asked to choose the most
      preferred specialty out of a list of options and to select the most important
      factors influencing their choice. RESULTS: A total of one hundred and sixty seven
      (102 UNIBEN and 65 NDU) students completed the study. A hundred (59.9%)
      respondents preferred surgery-related specialties while forty nine (29.3%)
      preferred medicine-related specialty. Forty five (26.9%) students preferred
      surgery while thirty six (21.6%) preferred obstetrics and gynaecology. Internal
      medicine and paediatrics were preferred amongst 18(10.8%) and 10(6.0%)
      respondents respectively. Other specialties were chosen to a lesser degree.
      Personal interest in 95(56.9%) participants was the most important factor
      influencing choice of medical specialties. CONCLUSION: The study highlights a
      general preference for core clinical specialties and surgery-related specialties
      especially surgery and obstetrics and gynaecology, amongst final year medical
      students. Personal interest was the most important factor influencing career
      choice. These findings have important implications for Nigeria's medical
      education and health care policy making.

PMID- 24872267
TI  - Maxillofacial and concomitant injuries in multiple injured patients at Korle Bu
      Teaching Hospital, Ghana.
AB  - BACKGROUND: Patients with maxillofacial injuries may sustain concomitant
      injuries. The presentation of other injuries may be the initial focus of
      attention of the primary attending surgeon who may miss the maxillofacial
      injuries to the detriment of the patient. OBJECTIVE: To determine the incidence
      of injuries associated with maxillofacial injuries at Korle Bu Teaching Hospital
      (KBTH) from January 2009 to December 2010. METHODS: A prospective study was
      carried out on patients who were referred to the Maxillofacial Unit of the
      University of Ghana Dental School and KBTH over the two years with maxillofacial
      injuries. Their age, sex, type of injury in the maxillofacial region, its
      aetiology and concomitant injuries were charted. The data was analysed using SPSS
      16.0 software. RESULTS: Two hundred and fifty eight (258) patients were seen of
      which 67 (26.0%) had concomitant injuries. The average age was 29.1 years. The
      peak incidence was in the age group 21-30 (N=73, 28.3%). 74% were male and 26.0%
      female. The commonest cause of injury was road traffic accident (RTA)
      (N=142;55.0%). 52.7% (N=136) of the patients had injuries of the maxillofacial
      region. 26.7% (N=69) had mandibular fractures, 19.4% (N=50) had middle third
      fractures and 8.1% (N=21) had fractures of both. Concomitant injuries were mainly
      orthopaedic (N=31;12%) and the head and spinal region (N=29;11.2%). CONCLUSION: A
      significant number of patients who suffer maxillofacial injuries also sustain
      injuries of other parts of the body at KBTH. Prompt multidisciplinary management
      may contribute to improved outcomes.

PMID- 24872268
TI  - Predictors of 24-hour drain volume after coronary artery bypass graft.
AB  - BACKGROUND: Excessive postoperative hemorrhage in cardiac surgery is a serious
      complication associated with adverse postoperative events. Also, its associated
      risk of re-exploration, places a high demand on hospital resources in terms of
      transfusion needs, ventilatory support requirements, intensive care support, and
      manpower requirements. OBJECTIVE: To determine predictors of 24-hour drain volume
      (pleural and mediastinal) after coronary artery bypass graft (CABG), in order to
      focus on preventive measures for patients with identified risk factors. PATIENTS
      AND METHODS: Fifty-four consecutive adult patients who had CABG at the Madras
      Medical Mission, Chennai, India in July 2008 were retrospectively studied. In
      order to determine risk factors for excessive post-operative bleeding, 11 pre
      operative, and 13 operative and 2 post-operative variables were analyzed using
      univariate analysis and multiple linear regression. RESULTS: Cardiopulmonary
      bypass was used for all the patients and anti-fibrinolytic in 13 (22.8%). No
      mortality was recorded. Mean 24-hour post-operative drain volume was 458 +/- 270
      ml (range 90-1230). Re-exploration for bleeding was required in 2 (3.5%)
      patients. Predictors of 24-hour drain volume were heparin therapy before
      commencement of CPB (p=0.024), intra-operative transfusion of fresh frozen plasma
      (p=0.010), and pre-operative serum ALT value (p=0.047). The strongest predictor
      was intra-operative transfusion of platelets (p=0.005). CONCLUSION: To guard
      against excessive post-operative haemorrhage after CABG, pre-operative
      stabilisation and correction of coagulation should be achieved. Also the
      administration of heparin intra-operatively should be individualized and not only
      based on dose per body weight.

PMID- 24872269
TI  - Ultrasound estimation of foetal gestational age by transcerebellar diameter in
      healthy pregnant nigerian women.
AB  - BACKGROUND: Ultrasonography has application in advanced obstetric practice
      through relatively detailed assessment of foetal anatomy and accurate assessment
      of gestational age (GA), especially during the first half of pregnancy. Foetal
      trans-cerebellar diameter (TCD) is an emerging parameter for gestational age
      determination among Africans. AIM: This study was carried out to establish
      baseline data for TCD at various corresponding gestational ages in Nigerian
      women, and evaluate the correlation between these two parameters. MATERIALS AND
      METHODS: Four hundred and fifty healthy singleton pregnant women, referred for
      antenatal scans were prospectively studied, following informed consent. Main
      inclusion criterion was certain last menstrual dates. A SONOACE chi6 ultrasound
      scanner, with a curvilinear probe and 3.5 MHz transducer, was used to measure the
      TCD. Data analysis was done and statistical significance set at p <= 0.05.
      RESULTS: TCD of the foetuses studied ranged from 11.9 mm (at 13 weeks) to 59.3mm
      (at 41 weeks) with a mean value 34.2 +/- 14.1mm.There was significant correlation
      between TCD and menstrual gestational age (r =0.984; p=0.000). TCD has a
      predictive accuracy of 96.9% with a standard error of +/- 10 days. CONCLUSION: A
      normogram of foetal TCD throughout gestation is established for Nigerian
      Africans.

PMID- 24872270
TI  - Pregnant women's knowledge and attitude to mother to child transmission of human
      immuno-deficiency virus in a rural community in Northwest Nigeria.
AB  - BACKGROUND: The high seroprevalence of HIV in Nigeria contributing to a huge
      burden of paediatric infection and with wide disparities in the various zones of
      the country needs to be addressed. The main strategy involves the prevention of
      mother to child transmission (MTCT) of HIV which remains the cornerstone of
      preventing the next generation from acquiring HIV. OBJECTIVES: To ascertain the
      knowledge and attitude of pregnant women in Northwest Nigeria to HIV and MTCT
      despite the low literacy level in the rural community. METHODS: This was a cross
      sectional study in which 450 pregnant women attending the booking clinic of a
      tertiary institution were recruited and interviewed using an interviewer
      administered semi-structured pre-tested questionnaires. The questionnaire
      assessed the pregnant women's knowledge related to HIV, MTCT of HIV, its
      prevention and respondents' attitude towards it. RESULTS: Of the 450 respondents,
      majority (96.2%) were aware of HIV. Most of them (78%) had adequate knowledge of
      MTCT of HIV. About half of the respondents knew that MTCT of HIV could be
      prevented by not breastfeeding, few agreed with taking of antiretroviral during
      pregnancy (28%) and giving new born antiretroviral (20.2%) as ways of preventing
      MTCT. CONCLUSION: The respondents in this study had a high level of awareness of
      HIV/AIDS, a good general knowledge of MTCT and attitude towards PMTCT but a below
      average knowledge of specific interventions on prevention of MTCT of HIV.

PMID- 24872271
TI  - Giant median lobe enlargement of the prostate mimicking advanced bladder tumour:
      a case report.
AB  - BACKGROUND: Giant Prostate (more than 100 g) is rare worldwide but Common in
      Africa. However Giant Median Lobe Enlargement is rare even in Africa. This
      Uncommon entity may pose a diagnostic puzzle especially when associated with
      haematuria, necroturia and suprapubic mass with background history of childhood
      haematuria. OBJECTIVE: To present a rare case of a giant benign median lobe
      enlargement of the prostate. METHODS: A 75 year old retired police officer
      presenting with 18 months history of intermittent total Painless hematuria,
      necroturia, increased frequency and feeling of incomplete bladder emptying. There
      was hesitancy and difficulty in passing Urine improved by manual pressure on the
      lower abdomen by the patient. Patient was evaluated clinically, radiologically,
      and also had Urine Cytology suggestive of malignancy. Cystoscopy and Biopsy
      revealed Inflammation. Patient sought medical Treatment in several hospitals and
      finally referred to our hospital. RESULTS: He was found to be clinically
      preserved, not pale, with a mobile suprapubic mass of about 12 cm above pubic
      symphysis,. Digital Rectal Examination revealed prostate not enlarged. Abdomino
      Pelvic ultrasound scan, Intravenous Urography, and Urethrocystography all
      suggested a huge bladder Tumour at the base occupying almost half of the bladder.
      Patient was prepared for Cystectomy and Urinary diversion. However, intra
      operative finding revealed a giant median lobe enlargement of the prostate (225
      g) with normal lateral Lobes, no other bladder mass seen. Transvesical
      prostatectomy was carried out. Patient did well postoperatively and was
      discharged. CONCLUSION: Giant Median Lobe Enlargement of the Prostate is rare and
      may present with hematuria, necroturia and supra pubic mass with normal digital
      rectal examination.

PMID- 24872272
TI  - Malignant transformation in von recklinghausen disease in a rural farmer
      presenting as huge metastatic soft tissue chest wall tumour: a case report.
AB  - INTRODUCTION: Although von Recklinghausen disease is relatively common at an
      incidence of 1 in 4000 live births, malignant transformation in a
      neurofibromatosis is quite rare estimated at about 5% therefore the importance of
      life-long follow up of all patients von Recklinghausen disease. CASE
      PRESENTATION: This is a case report of a 45-year old Nigerian-Ibibio male farmer
      who presented with six months history of rapid growth in one of the numerous skin
      nodules which had been present since his teenage age. The clinical diagnosis of
      malignant change in von Recklinghausen's disease was confirmed by histopathologic
      examination of an incisional biopsy specimen. Radiological investigations also
      showed the metastatic status of the disease. The patient could not afford the
      cytotoxic chemotherapeutic agents prescribed. He therefore left the hospital and
      failed to return when a free-treatment voucher was ready for treatment in the
      following two days. He is assumed dead at home. CONCLUSION: Lifelong follow up
      for von Recklinghausen disease is emphasized to enable early detection of
      malignant change and also expansion of the national health insurance scheme to
      benefit the unemployed citizens.

PMID- 24872273
TI  - Simultaneous pectoralis major muscle and orbital metastasis as the primary
      presentation of pulmonary adenocarcinoma.
AB  - A 63-year old male with chronic shoulder pain and painful left eye with binocular
      diplopia of sudden onset was seen independently by Ophthalmologists and his
      family Doctor and investigated first non-invasively where masses were found both
      in the orbit and pectoralis muscle. Further investigations including biopsy
      confirmed non-small cell lung carcinoma with metastasis to these sites; unusual
      sites of tumour metastasis and the first reporting of such tumour behaviour. 

PMID- 24872274
TI  - Xeroderma pigmentosum in Ghanaians: a report of three cases and review of
      literature.
AB  - BACKGROUND: Xeroderma pigmentosum is an autosomal recessive disease with sun
      sensitivity, photophobia, early onset of freckling, and subsequent neoplastic
      changes on sun-exposed surfaces. There is cellular hypersensitivity to UV
      radiation and to certain chemicals in association with abnormal DNA repair.
      Patients with defective DNA nucleotide excision repair (NER) have defects in one
      of seven NER genes; xeroderma pigmentosum variants have normal NER and a defect
      in a polymerase gene. STUDY DESIGN: This is a case presentation of three patients
      with the features of xeroderma pigmentosum, aged 48, 15, and 14 years. The latter
      two patients were females. Each presented with areas of hyper-and hypo
      pigmentation over sun exposed body surfaces. Each patient had a minimum of two
      cutaneous malignancies, distributed on the upper chest, face or scalp. RESULTS:
      The first and third patients had their lesions surgically excised and the defects
      were skin grafted. The second patient was treated with radiotherapy. All the
      lesions presented were confirmed histologically as squamous cell carcinoma. No
      recurrence of the malignancies has been noticed. CONCLUSION: Xeroderma
      pigmentosum is not rare in Ghana. Early recognition of the disease is necessary
      to avoid morbidity and mortality from malignant complications. The use of other
      treatment modalities such as sunscreens, oral retinoids, and chemical therapy
      with 5-fluorouracil is discussed.

PMID- 24872275
TI  - Species of Neoperla (Plecoptera: Perlidae) from Yunnan Province, China.
AB  - Two new species of the genus Neoperla are described from Yunnan Province, China:
      Neoperla lihuae Li & Muranyi, sp. nov. and Neoperla yanlii Li & Wang, sp. nov.
      They are compared with related congeners. Brief comments on the taxonomy of N.
      cavaleriei (Navas, 1922), N. limbatella Navas, 1933, N. obscurofulva Wu, 1962 and
      N. lui Du, 2004 are also presented. 

PMID- 24872276
TI  - Revision of Chinese Dilaridae (Insecta: Neuroptera) (Part I): species of the
      genus Dilar Rambur from northern China.
AB  - The pleasing lacewing genus Dilar Rambur is a dominant group of the family
      Dilaridae in Asia and is diverse in China with 18 described species. Herein we
      record five species of Dilar. Three species, i.e. Dilar hastatus sp.nov., Dilar
      spectabilis sp.nov. and Dilar taibaishanus sp.nov. are described as new to
      science. Dilar sinicus Nakahara and Dilar septentrionalis Navas are also
      redescribed. A key to the species of Dilar from northern China is given.  

PMID- 24872277
TI  - Taxonomic study of the Pagurus forbesii "complex" (Crustacea: Decapoda:
      Paguridae). Description of Pagurus pseudosculptimanus sp. nov. from Alboran Sea
      (Southern Spain, Western Mediterranean Sea).
AB  - Study of hermit crabs from Alboran Sea has allowed recognition of two different
      morphological forms under what had been understood as Pagurus forbesii. Based on
      morphological observations with various species of Pagurus, and molecular
      studies, a new species is described as P. pseudosculptimanus. An overview of
      species of Pagurus from the eastern Atlantic and Mediterranean Sea is provided. 

PMID- 24872278
TI  - A new species of spiny-tailed iguanid lizard (Iguania: Stenocercus) from
      northwestern Peru.
AB  - We describe a new species of Stenocercus from the interandean valley of Rio
      Chotano on the Amazonian slope of the northern portion of the Cordillera
      Occidental of Peru (Cajamarca Region), at elevations of between 1997 and 2318 m.
      Stenocercus arndti sp. nov. differs from other Stenocercus, except from S.
      bolivarensis, S. carrioni, S. chlorostictus, S. crassicaudatus, S. empetrus, S.
      eunetopsis, S. simonsii, and S. torquatus, in having granular scales on the
      posterior surface of the thighs, two caudal whorls per autotomic segment,
      mucronate caudal scales, and distinct longitudinal row of enlarged vertebral
      scales. However, Stenocercus arndti sp. nov. is easily distinguished from these
      species in having a bold black transversal band at midbody that extends
      ventrolaterally in adult males.

PMID- 24872279
TI  - Taxonomic study of the leafhopper genera Gredzinskiya Dworakowska and Musbrnoia
      Dworakowska (Hemiptera: Cicadellidae: Typhlocybinae: Erythroneurini) with
      descriptions of seven new species.
AB  - The genera Gredzinskiya Dworakowska and Musbrnoia Dworakowska are revised and
      seven new species are described: Gredzinskiya lamellaris, G. serrata, G.
      spinalis, G. zhangae, Musbrnoia angusta, M. corollaris and M. lata spp. nov..
      Habitus photos, illustrations of male genitalia and keys to adult males for both
      genera are provided. 

PMID- 24872280
TI  - Periclimenaeus denticulodigitus sp. nov. (Crustacea: Decapoda: Palaemonidae:
      Pontoniinae), from Heron Island, Queensland, Australia.
AB  - An unusual species of the genus Periclimenaeus Borradaile, 1915 (Crustacea:
      Decapoda: Palaemonidae Pontoniinae) from Heron Island, Queensland, Australia,
      collected by Dr Niel Bruce in 1979, is described and illustrated. Periclimenaeus
      denticulodigitus sp. nov., an ascidian associate was collected from coral reef at
      7.0 m and presents some interesting new features. It increases to 17 the number
      of Periclimenaeus known from Heron Island, Queensland, and to 28 the number of
      species known from Australia. The new species has the second pereiopod fingers
      minutely denticulate and unique to the genus. 

PMID- 24872281
TI  - A new species of Amazophrynella (Anura:Bufonidae) from the southwestern part of
      the Brazilian Guiana Shield.
AB  - Amazophrynella is a genus of the family Bufonidae, currently represented by three
      species. The type species of the genus, Amazophrynella minuta, however, is a
      complex of species occurring throughout the Amazonian biome. This group remains
      problematic taxonomically; the difficulty lays principally in the lack of
      diagnostic characters in the original description of A. minuta, the lack of
      molecular data and refined taxonomic comparison of individuals through its wide
      distribution. We describe a new species of the genus Amazophrynella, distributed
      in the southwestern part of the Guiana Shield of Brazil based on a series of
      morphological and molecular characters. The new species differs from others of
      the genus by presenting a slightly truncated triangular snout, ventral texture
      covered by many fine granules, white belly covered with black spots and by
      fifteen molecular autapomorphies in the 16S rDNA fragment. Uncorrected p
      distances of a fragment of the 16S mitochondrial rDNA gene revealed high
      divergence among other Amazophrynella species (9%-14%). Additionally we provide a
      new diagnosis of topotypic material of Amazophrynella minuta including molecular
      data. Our results show the existence of a subestimated diversity in the genus
      Amazophrynella.  

PMID- 24872282
TI  - The Mediterranean and Eastern Atlantic species of Spinolambrus Tan & Ng, 2007: S.
      macrochelos (Herbst, 1790), S. notialis (Manning & Holthuis, 1981), and S.
      verrucosus (Studer, 1883), with a note on the identity of Lambrus spinosissimus
      Osorio, 1923 (Crustacea: Decapoda: Brachyura: Parthenopidae).

PMID- 24872283
TI  - Occurrence and distribution of Pseudoscalibregma and Scalibregma (Annelida,
      Scalibregmatidae) in the deep Nordic Seas, with the description of Scalibregma
      hanseni n. sp.
AB  - Until recent years, only a few scalibregmatid species have been known from the
      Nordic Seas, largely from shelf and coastal waters. Access to a large collection
      from deep areas has made it possible to provide more knowledge on the diversity
      of this group in the area. Pseudoscalibregma parvum (Hansen, 1879) is here
      redescribed. The species has a wide geographic distribution in the Nordic Seas,
      the Barents Sea, and the Kara Sea. Type specimens of Eumenia longisetosa Theel,
      1879 were found to be similar to specimens of P. parvum, confirming the synonymy
      of the species. A new species, Scalibregma hanseni n. sp., is described from
      specimens found on the continental slope. It is particularly characterised by
      having three pairs of rather simple branchiae. Both P. parvum and S. hanseni have
      small spines in the most anterior chaetiger(s), resembling spines reported from a
      few other Pseudoscalibregma and Scalibregma species and supporting the need to
      emend the genus diagnosis of Pseudoscalibregma. Scalibregma abyssorum Hansen,
      1879 was reassessed and considered to be a nomen dubium. Scalibregma inflatum,
      which has a wide distribution along the Norwegian coast and continental shelf, is
      found to be restricted to depths above about 900 m. Depths from 600-800 m on the
      continental slope represent a transition zone with fluctuations between temperate
      North Atlantic water (about 7 degrees C) and cold Norwegian Sea water (below 0
      degrees C). The three species coexist in this zone, whereas P. parvum and S.
      hanseni n. sp. extend down to 1700 and 1200 m, respectively, on the slope at
      temperatures below 0 degrees C.

PMID- 24872284
TI  - Taxonomic review of the genus Paratalanta Meyrick, 1890 (Lepidoptera: Crambidae:
      Pyraustinae) from China, with descriptions of two new species.
AB  - This study deals with the taxonomy of seven species and subspecies of the genus
      Paratalanta Meyrick in China. Among them, P. furcata sp. nov. and P. annulata sp.
      nov. are described as new. The male of P. stachialis Toll & Wojtusiak, 1957 is
      described for the first time. Images of adults and illustrations of both male and
      female genitalia are provided, along with a key to all the known Chinese species
      and a map showing their distribution. 

PMID- 24872285
TI  - New records of predaceous midges from the Middle East, with the description of
      two new species (Diptera: Ceratopogonidae).
AB  - Two new distinctive species of predaceous biting midges of the tribe
      Ceratopogonini are described and illustrated from the Middle East. Brachypogon
      freidbergi sp. nov., with a unique Y-shaped gonostylus, is recorded from Israel.
      We also provide the first records of Brachypogon vitiosus (Winnertz) and B.
      aethiopicus (Clastrier, Rioux & Descous) from this country, and a key to the
      adult males of the genus Brachypogon Kieffer from the Middle East. Ceratopogon
      azari sp. nov., described from Lebanon, shows a distinctive structure of the male
      genital apparatus, and is the southernmost species of that genus in the Western
      Palaearctic. 

PMID- 24872286
TI  - The nudibranch names mentioned as n.sp. in Bergh (1861) are almost all nomina
      nuda (Gastropoda: Heterobranchia: Nudibranchia).
AB  - In a publication in Danish from 1861, Bergh described the nematocysts found in a
      number of nudibranch species. Many of the species had been described previously,
      but a number were new and given names, but without a description. These species
      are nomina nuda. We have translated the "descriptions", including the foot-notes,
      and reproduced the original plate to show that only the nematocysts (real or
      assumed) were described. The only species given a short description fulfilling
      the requirements of the ICZN is Pleurophyllidia quadrilateralis, which was
      described as the only species in the new genus Sancara. This in turn was shown to
      be a junior synonym of Linguella de Blainville, 1823. All the species were
      subsequently described anatomically in detail and made valid in a number of
      papers, and most of the type material is located in the Zoological Museum,
      Copenhagen (Natural History Museum of Denmark). The names in current use have
      been given. 

PMID- 24872287
TI  - Notes on the genera Peritropisca Carvalho & Lorenzato and Rewafulvius Carvalho
      (Hemiptera: Heteroptera: Miridae: Cylapinae), with the description of a new
      species of Peritropisca from Indonesia.
AB  - The genera Peritropisca Carvalho & Lorenzato, 1978 and Rewafulvius Carvalho, 1972
      are redescribed. A description of a new species of the genus Peritropisca from
      Indonesia-P. laticostata sp. nov. and a redescription of P. bituberculata
      Carvalho & Lorenzato, 1978 are provided. The genus Euchilofulviella Gorczyca,
      1999 is proposed as a junior synonym of Rewafulvius Carvalho, 1972 syn. nov. A
      color habitus picture of the adult and male genitalia drawings of each treated
      species are provided. A key to the genus Peritropisca is given. 

PMID- 24872288
TI  - A new six-pored Amphisbaena (Squamata: Amphisbaenidae) from the coastal zone of
      northeast Brazil.
AB  - We describe a new Amphisbaena from the Brazilian coastal zone at the
      municipalities of Guamare and Macau, state of Rio Grande do Norte. The new
      species, Amphisbaena littoralis sp. nov., is characterized by six precloacal
      pores, 252-264 body annuli, 30-34 tail annuli with autotomy on the 6<sup>th</sup>
      tail annuli, 20-22 dorsal and 21-24 ventral segments to the midbody annulus. 

PMID- 24872289
TI  - A new species of Supramontana Carbayo & Leal-Zanchet (Platyhelminthes,
      Continenticola, Geoplanidae) from the Interior Atlantic Forest.
AB  - Supramontana argentina sp. nov. (Platyhelminthes, Continenticola, Geoplanidae)
      from north-eastern Argentina is herein described. The new species differs from
      Supramontana irritata Carbayo & Leal-Zanchet, 2003 from Brazil, the only species
      of this genus so far described, by external and internal morphological
      characters. Supramontana argentina sp. nov. is characterized by having a colour
      pattern with a yellowish median band, thin para-median black stripes, and two
      dark grey lateral bands on the dorsal surface. The most outstanding features of
      the internal morphology are a ventral cephalic retractor muscle almost circular
      in cross section, prostatic vesicle extrabulbar, tubular and very long, and penis
      papilla conical and blunt with a sinuous ejaculatory duct. 

PMID- 24872291
TI  - A new species of Iapir Py-Daniel, Fonseca & Barbosa (Coleoptera: Myxophaga:
      Torridincolidae) from Brazil with key to species of the genus.
AB  - The genus Iapir is known only from Brazil, currently with five species. This
      genus is characterized by the lack of a tooth on the hind margin of
      metatrochanter and a semi-lunar depression prolonged toward apex of the last
      ventrite on female specimens. Herein we describe an additional species, Iapir
      vanini sp. nov., collected in southeastern Brazil in Santa Teresa (type
      locality), Castelo, and Domingos Martins municipalities, in Espirito Santo State.
      The presence of a fringe of setae on the anterior face of front tibiae and on the
      posterior face of hind tibiae, and the male genitalia with an oblique apex in
      lateral view and bearing tufts of seta on distal third, distinguish this species
      from other Iapir. A key for identification of the species of Iapir is presented. 

PMID- 24872290
TI  - Two new Larainae species from Guayana region, Venezuela (Coleoptera: Elmidae).
AB  - Two new species of the subfamily Larainae (Insecta: Coleoptera: Elmidae),
      Hexanchorus angeli n. sp. and Hypsilara autanai n. sp., are described from Guyana
      region in Venezuela. We provide habitus photographs, detail drawings of both male
      and female genitalia, and description of morphological features important for
      discrimination of the new species. Molecular differences within genera were
      measured using 816bp fragment of mtDNA gene for cytochrome oxidase c subunit I.
      Sequence divergences among species are discussed. 

PMID- 24872292
TI  - Taxonomic revision of the species of Parvanachis Radwin, 1968 (Gastropoda:
      Columbellidae) from the Gulf of Panama.
AB  - Species of Parvanachis Radwin, 1968 collected from the Gulf of Panama are
      anatomically characterized and taxonomically revised. Six species are reported to
      occur in the region: P. pygmaea (Sowerby, 1832), P. pardalis (Hinds, 1843), P.
      diminuta (C.B. Adams, 1852), P. albonodosa (Carpenter, 1857), P. milium (Dall,
      1916), and P. dalli Bartsch, 1931. Of these six, three are confirmed as
      described. P. milium was not found in new collections or the previous survey
      collection and may be more common further south. P. dalli is a synonym of P.
      pygmaea; and P. albonodosa (auct.) is renamed, because the type material
      represents a different species. Two new species are described, P. dichroma and P.
      adamsi. P. pardalis, based on anatomy and shell and radular morphology, is
      referred to the genus Anachis, and Costoanachis nigricans (Sowerby, 1844), based
      on anatomy and shell morphology, is transferred to Parvanachis. The resulting
      seven species of Parvanachis constitute two groups; one (including the type
      species) with smaller shells and a simple penis morphology, and a group of four
      larger species with more complex penis morphology. 

PMID- 24872293
TI  - Inocellia rara sp. nov. (Raphidioptera: Inocelliidae), a new snakefly species
      from Taiwan, with remarks on systematics and biogeography of the Inocelliidae of
      the island.
AB  - A new species of the snakefly genus Inocellia Schneider, 1843 from Taiwan is
      described: Inocellia rara sp. nov. It represents the third species in the family
      Inocelliidae and the first record of the Inocellia fulvostigmata species group
      from Taiwan. 

PMID- 24872294
TI  - Description of a new species of Terminalichus (Acari: Trombidiformes:
      Tenuipalpidae) from China.
AB  - A new species Terminalichus sanya Xu & Fan sp. nov. (Acari: Tenuipalpidae) on
      Terminalia catappa L. (Combretaceae) from China is described and illustrated. The
      ontogenetic changes in ventral and leg chaetotaxy on the female, deutonymph,
      protonymph and larva are presented. The generic definition of Terminalichus is
      updated and a key to the world species is provided. 

PMID- 24872295
TI  - A new frog species (Myobatrachidae: Uperoleia) from the Northern Deserts region
      of Australia, with a redescription of U. trachyderma.
AB  - The frog genus Uperoleia (Myobatrachidae) is species rich, with the greatest
      diversity in the northern monsoonal region of Australia. Due in part to their
      small body size, conservative morphology and distribution in diverse habitats,
      the genus is likely to harbor cryptic species. A recent study (Catullo et al.
      2013) assessed region-wide genetic, acoustic and phenotypic variation within four
      species in northern Australia. Catullo et al. (2013) presented multiple lines of
      evidence that the widespread U. trachyderma comprises distinct allopatric western
      and eastern lineages within the Northern Deserts bioregion of Australia. Here we
      formally describe the western lineage as U. stridera sp. nov. and redescribe the
      eastern (type) clade as U. trachyderma. The new species can be distinguished from
      U. trachyderma by fewer pulses per call, a faster pulse rate, and the lack of
      scattered orange to red flecks on the dorsum. The description of U. stridera sp.
      nov. brings the number of Uperoleia species to 28, by far the largest genus in
      the Myobatrachidae, and further highlights the Australian monsoonal tropics as a
      region of high endemism.

PMID- 24872296
TI  - The genus Paracholula (Hemiptera: Heteroptera: Lygaeoidea: Rhyparochromidae:
      Rhyparochrominae: Myodochini).
AB  - The genus Paracholula Harrington has been represented by two species, P. picta
      (Fab) and P. thoracica (Distant), both recorded from Mexico. Individuals of one
      population from Guerrero were studied and compared with individuals of both
      species from different collections, including the types. Using scanning electron
      micrographs of different structures, and observation of the male genitalia of
      some individuals, together with a close examination of all the individuals from
      the population from Guerrero, we discovered, that there is great variation in all
      the structures and that some characters that were used to separate the two
      species are present within the population from Guerrero. Therefore we synonymize
      both species, stating that the valid name for this species is Paracholula picta
      (Fab). Descriptions and illustrations of all the immature stages from the
      Guerrero population are included. Notes about host plants, biology and
      distributional records are also included. 

PMID- 24872297
TI  - Three new species and new distributional records of Oecetis McLachlan 1877
      (Trichoptera: Leptoceridae: Leptocerinae) from Brazil.
AB  - The genus Oecetis is widespread over the world, being most diverse in tropical
      areas, especially in the Australian Region. Of about 400 described species, only
      34 occur in the Neotropical Region. Herein, we describe and illustrate three new
      species of Oecetis from Brazil: Oecetis angelae sp. nov., O. danielae sp. nov.
      and O. iara sp. nov. Furthermore, O. doesburgi, O. dominguezi, and O. knutsoni
      are recorded for the first time in Brazil. Also, we provide new state records for
      7 species: O. amazonica, O. connata, O. excisa, O. fibra, O. iguazu, O.
      inconspicua, and O. paranensis. 

PMID- 24872298
TI  - Two new species of cheilostome bryozoans from the South Atlantic Ocean .
AB  - Two new species of cheilostome bryozoans are described from Bahia and Espirito
      Santo States, Brazil-Calyptooecia conuma n. sp. and Hippotrema fissurata n. sp.
      Both genera are registered for the first time in the South Atlantic Ocean. Inter
      alia, Calyptooecia conuma n. sp. is characterized by the presence of dimorphic
      brooding zooids with relatively small orifices and no perioral tubercles,
      contrasting with bigger non-brooding zooids having larger orifices surrounded by
      perioral tubercles. Hippotrema fissurata n. sp. differs from congeners in colony
      morphology and colour, in details of the ooecium and in zooidal metrics.
      Specimens were collected on varied substrata, commonly calcareous nodules and
      shells as well as other bryozoans and sponges.  

PMID- 24872299
TI  - A new species of Munidopsis from a seamount of the Southwest Indian Ocean Ridge
      (Decapoda: Munidopsidae).
AB  - Wood and whale bone colonisation experiments were undertaken on the Southwest
      Indian Ocean Ridge, 18 November 2009. Later, 14 December 2011, squat lobsters
      were recovered from the submerged wood and assigned to Munidopsis sp. Further
      study indicated that the specimens belonged to the group of species having a
      rostrum without lateral spines, presence of two strong epigastric spines, unarmed
      abdominal segments, one dorsal eye-spine, and with the second pereiopod not
      reaching the end of the first. They were similar to M. hemingi Alcock & Anderson,
      1899 but differed in that the epigastric spines are well developed (vs. tubercles
      in M. hemingi), the lateral margins of the carapace are straight (vs. more convex
      in M. hemingi), the eye has a tubercular process mediodorsally (vs. a papilliform
      spinule at mesial angle) and the epipods on the fourth pereiopod were absent (vs.
      present in M. hemingi). Consequently the Munidopsis specimens from the Southwest
      Indian Ocean Ridge were considered to be an undescribed species. 

PMID- 24872300
TI  - Denopelopia moema, a new Tanypodinae (Diptera: Chironomidae) from the Neotropical
      Region.

PMID- 24872302
TI  - Taxonomic revision of the genus Chaetocnemistoptera Borgmeier (Diptera:
      Phoridae), with the description of five new species.
AB  - The Neotropical genus Chaetocnemistoptera is herein revised. Five new species are
      described-C. lobata, sp. nov., C. magdalena, sp. nov., C. phaeonota, sp. nov., C.
      pityropyga, sp. nov., C. trichopoda, sp. nov. The hypopygia of the previously
      described Chaetocnemistoptera palpalis (Borgmeier) and C. formosa (Borgmeier) are
      illustrated. The female holotype of Chaetocnemistoptera semifurcata (Borgmeier)
      could not be associated with any male specimen. A species identification key is
      provided and comments on the homology of structures and on species relationships
      are made. 

PMID- 24872303
TI  - Remarks on the deep-sea genus Chalarostylis (Cumacea: Lampropidae).
AB  - Chalarostylis is a deep-sea genus close to Hemilamprops but easily distinguished
      from the latter mainly by its robust first pereopod. However, this appendage is
      frequently broken off at the anterior margin of the basis, making the
      identification of the species of the genus difficult. Regarding Hemilamprops
      brenkei, both the adult male holotype and the additional specimens herein
      reported from the Weddell Sea and the Guinea, Argentine and Brazilian Basins
      exhibit a huge first pereopod. Thus, this species is transferred to Chalarostylis
      and its description completed. Two other species until now in Hemilamprops, H.
      canadensis and H. longisetae are also transferred to Chalarostylis. In addition,
      an unknown species of Chalarostylis from the Bay of Biscay for which no name is
      given is briefly described. The diagnosis of this genus is emended.  

PMID- 24872304
TI  - Water mites of the genus Brachypoda Lebert, 1879 (Acari: Hydrachnidia: Aturidae)
      from South Korea and the Russian Far East.
AB  - In this study, four water mites of the genus Brachypoda (Acari: Hydrachnidia:
      Aturidae) are reported from South Korea and the Far East of Russia. Brachypoda
      (Ocybrachypoda) milicaae sp. n. (South Korea), B. (Ocybrachypoda) sokolowi sp. n.
      (Russia) and B. (Eubrachypoda) rossica sp. n. (Russia) are described as new for
      science. The latter species is the second representative of the subgenus
      Eubrachypoda Tuzovskij, 2004, previously known only from Lake Biwa in Japan. A
      new record of Brachypoda rubidata Kim & Chung, 1996, a species so far known only
      from a pond in Bosung (South Korea), is given.  

PMID- 24872305
TI  - New Leptotarsus from the Early Cretaceous of Brazil and Spain: the oldest members
      of the family Tipulidae (Diptera).
AB  - New species of Leptotarsus (Tipulidae s.str.) are described from the Early
      Cretaceous beds of Brazil (Santana Fm. Aptian/Albian, ca. 112 Mya) and Spain (La
      Huerguina Fm., Late Barremian, ca. 126 Mya), vis. L. grimaldii sp. nov., L.
      cretaceus sp. nov., L. martinsnetoi sp. nov., L. buscalioniae sp. nov., L.
      ibericus sp. nov. and L. contractus sp. nov. Males of three species possess
      extremely long antennae. The fossils are the oldest representatives of the genus
      Leptotarsus, and the oldest known members of the family Tipulidae.  

PMID- 24872306
TI  - A new Imogine species (Turbellaria: Polycladida: Stylochidae) associated with
      rock oysters (Saccostrea cucullata) from the Persian Gulf, with a review of the
      genus.
AB  - A new species of acotylean polyclad, Imogine qeshmensis sp. nov. is described
      from Qeshm Island, Persian Gulf, Iran. I. qeshmensis is characterized by the
      number and arrangement of the tentacular, cerebral and frontal eyes, a body
      margin with opaque white bands and eyespots and a male genital complex with an
      highly muscular seminal vesicle equal in size to the prostatic vesicle. 

PMID- 24872308
TI  - Hamacantha (Hamacantha) boomerang sp. nov. from deep-sea coral mounds at Campos
      Basin, SW Atlantic, and redescription of H. (H.) schmidtii (Carter, 1882)
      (Hamacanthidae, Poecilosclerida, Demospongiae).
AB  - There are 22 species of Hamacantha registered from all over the world, and
      frequently from deep-waters, only two of which had previously been reported from
      the SW Atlantic. Here we describe a third species for this area, Hamacantha (H.)
      boomerang sp. nov., collected from deep-sea coral mounds at Campos Basin (off Rio
      de Janeiro state). We found oxeas 271-630 um long, diancistras in three size
      classes, 125-155, 45-69 and 20-29 um, and toxas, 58-82 um. This is the only
      Hamacantha combining oxeas and toxas, but the latter are very rare. The species
      approaches the Caribbean H. (H.) schmidtii (Carter, 1882), where we observed
      oxeas 390-495 um long, and diancistras in three size classes, 109-124,  44-54 and
      26-41 MUm, however toxas appear to be absent. Both species are clearly distinct
      by micrometric values, as well as the overall morphology of the smaller
      diancistras, distinct from the intermediate category in the new species, but
      quite similar in H. (H.) schmidtii. Hamacantha (Vomerula) falcula approaches the
      new species very closely in microsclere dimensions and morphology, but is set
      apart by its styloid and smaller megascleres. 

PMID- 24872307
TI  - A new Shivaphis species (Hemiptera: Aphididae) on the Chinese endemic plant,
      Pteroceltis tatarinowii.
AB  - A new species of aphid in subfamily Calaphidinae, Shivaphis pteroceltis sp. n.,
      is described from China. This aphid feeds on Pteroceltis tatarinowii, an endemic
      tree commonly planted as an ornamental in China and used in the production of
      Xuan paper. The life cycle is described, and the descriptions of fundatrices,
      apterous and alate viviparae, oviparae and males are provided. COI sequences have
      been deposited in Genbank, and the type specimens are deposited in the National
      Zoological Museum of China, Institute of Zoology, Chinese Academy of Sciences,
      Beijing and Forestry Bureau of Central District, Zaozhuang City, Shandong
      Province, China. 

PMID- 24872309
TI  - A new phytophagous eulophid wasp (Hymenoptera: Chalcidoidea: Eulophidae) that
      feeds within leaf buds and cones of Pinus massoniana.
AB  - Aprostocetus pinus sp. nov. (Chalcidoidea: Eulophidae) is newly described as a
      leaf bud and microstrobilus pest of Pinus massoniana (Pinales: Pinaceae), an
      important afforestation species in southeast China. Both sexes of the parasitoid
      are described and illustrated.  

PMID- 24872310
TI  - The status of the Australian genus Caridinides Calman, 1926 (Crustacea: Decapoda:
      Atyidae) with reference to recent phylogenetic studies.

PMID- 24872312
TI  - Open-circuit voltage improvement in tantalum-doped TiO2 nanocrystals.
AB  - Enhanced electron concentration derived from Ta(5+) doping is responsible for the
      open-circuit voltage improvement due to the upward shift of the Fermi level, but
      the oxygen defects generated retard the negative shift of the Fermi level. By
      mediating the trap states, highly efficient DSSC devices could be achieved. 

PMID- 24872313
TI  - Open access support groups for people experiencing personality disorders: do
      group members' experiences reflect the theoretical foundations of the SUN
      project?
AB  - OBJECTIVES: The SUN Project is an innovative, open access support group, based in
      the community, for people experiencing personality disorders, developed in
      response to UK Department of Health policy advocating improvements in personality
      disorders services. The aim of this article is to critically explore where and
      how the theoretically informed model underpinning the SUN Project is reflected in
      the view and experiences of people attending the project. DESIGN: This article
      reports an in-depth, qualitative interview-based study employing a critical
      realist approach. METHODS: As part of a larger study about self-care and mental
      health, in-depth qualitative interviews were held with 38 people new to the SUN
      Project, and again 9 months later. Data were extracted that were relevant to core
      components of the project model and were subjected to thematic analysis. The
      critical realist approach was used to move back and forth between empirical data
      and theory underpinning the SUN project, providing critical insight into the
      model. RESULTS: Participant accounts were broadly concordant with core components
      of the SUN Project's underlying model: Open access and self-referral; group
      therapeutic processes; community-based support; service users as staff. There
      were some tensions between interviewee accounts and theoretical aspects of the
      model, notably around the challenges that group processes presented for some
      individuals. CONCLUSIONS: The model underlying the SUN Project is useful in
      informing good practice in therapeutic, community-based peer support groups for
      people experiencing personality disorders. Careful consideration should be given
      to a limited multi-modal approach, providing focused one-to-one support for
      vulnerable individuals who find it hard to engage in group processes.
      PRACTITIONER POINTS: Facilitated peer support groups based in the community may
      act as a powerful therapeutic resource for people experiencing personality
      disorders. Promoting open access and self-referral to support groups may increase
      feelings of empowerment and engagement for people experiencing personality
      disorders. Some individuals experiencing personality disorders who could
      potentially benefit from therapeutic groups may need focused one-to-one support
      to do so.

PMID- 24872311
TI  - Progressive resistance training in polycystic ovary syndrome: can pumping iron
      improve clinical outcomes?
AB  - Polycystic ovary syndrome (PCOS) is the most common endocrine disorder and cause
      of subfertility in women. The etiology of PCOS has not been fully elucidated;
      however, insulin resistance has been shown to exacerbate the disease process due
      to its effect on androgen synthesis. Progressive resistance training (PRT) is an
      anabolic exercise modality that can improve skeletal muscle size and quality
      (metabolic capacity), and studies have consistently shown that PRT can increase
      insulin sensitivity in type 2 diabetes and other cohorts. However, PRT is not
      currently recommended or routinely prescribed in PCOS. The objective of this
      article was to provide a rationale for the application of PRT in the management
      and treatment of PCOS. This will be accomplished by (1) overviewing the
      pathophysiology of PCOS with emphasis on the etiological role of insulin
      resistance; (2) summarizing the effectiveness of PRT in treating insulin
      resistance; (3) presenting evidence that PRT is feasible to prescribe in women
      with PCOS; and (4) providing general recommendations for PRT to complement
      existing guidelines for aerobic training in this cohort. We also provide
      recommendations for future research. 

PMID- 24872315
TI  - Self-assembly of a neutral platinum(II) complex into highly emitting
      microcrystalline fibers through metallophilic interactions.
AB  - The solvent-assisted self-assembly of a blue-emitting neutral platinum(II)
      complex into micrometer-long and highly crystalline fibers has been achieved. The
      aggregates show highly efficient (quantum yield up to 74%) polarized yellow
      orange light emission, as a consequence of their high degree of supramolecular
      order imparted by weak non-covalent intermolecular (metal...metal and pi-pi)
      interactions.

PMID- 24872318
TI  - Relevant role of PKG in the progression of fibrosis induced by TNF-like weak
      inducer of apoptosis.
AB  - TNF-like weak inducer of apoptosis (TWEAK) is an inflammatory cytokine that
      activates the FGF-inducible 14 receptor. Both TWEAK and the FGF-inducible 14
      receptor are constitutively expressed in the kidney. TWEAK has been shown to
      modulate several biological responses, such as inflammation, proliferation,
      differentiation, and apoptosis, that contribute to kidney injury. However, the
      role of TWEAK in fibrosis and TWEAK-activated intracellular signaling pathways
      remain poorly understood. We tested the hypothesis that TWEAK can be a potent
      inducer of renal fibrosis by increasing transforming growth factor (TGF)-beta1
      expression (a well-known switch in the fibrosis process) through PKG-I
      downregulation. We showed that in human mesangial cells, TWEAK increased TGF
      beta1 expression and activity, leading to higher levels of the extracellular
      matrix protein fibronectin and decreased PKG-I expression and activity via the
      Ras pathway. PKG-I activation with 8-bromo-cGMP, Ras inactivation with dominant
      negative Ras, or Ras pathway inhibition with the ERK1/2 inhibitor PD-98059
      resulted in the prevention of TWEAK-induced TGF-beta1 upregulation. In vivo,
      exogenous administration of TWEAK to wild-type mice downregulated kidney PKG-I
      and increased kidney TGF-beta1 expression. These effects were blunted in H-Ras
      knockout mice. Together, these data demonstrate, for the first time, the key role
      of PKG-I in TGF-beta1 induction by TWEAK in kidney cells. 

PMID- 24872316
TI  - High-salt diet blunts renal autoregulation by a reactive oxygen species-dependent
      mechanism.
AB  - High dietary salt is common in Western countries and is an important contributor
      to increased cardiovascular disease. Autoregulation of renal blood flow (RBF) and
      glomerular filtration rate (GFR) is an essential function of the renal
      microcirculation that could be affected by excessive dietary salt. High salt (HS)
      increases renal ROS generation partly by the enzyme NADPH oxidase. We
      hypothesized that a HS diet would impair autoregulation via NADPH oxidase
      dependent ROS generation. The role of NADPH-dependent ROS production on the
      blunted autoregulatory response with a HS diet was assessed in vitro and in vivo
      using the blood-perfused juxtamedullary nephron preparation and anesthetized
      rats, respectively. The increase in renal lipid peroxidation and p67(phox)
      expression induced by HS was prevented by apocynin treatment. Control afferent
      arterioles exhibited normal autoregulatory behavior in response to acute
      increases in renal perfusion pressure, whereas arterioles from HS rats exhibited
      a blunted response. Autoregulatory behavior in HS rats was restored in vitro by
      acute exposure to the NADPH oxidase inhibitor apocynin. At the whole kidney
      level, in vivo experiments showed that both RBF and GFR declined in HS rats when
      left kidney renal perfusion pressure was reduced from ambient to 95 mmHg, whereas
      control rats maintained stable GFR and RBF consistent with efficient
      autoregulatory behavior. Apocynin treatment improved in vivo autoregulatory
      behavior in HS rats and had no detectable effect in normal salt diet-fed rats.
      These data support the hypothesis that impaired renal autoregulatory behavior in
      rats fed a HS diet is mediated by NADPH oxidase-derived ROS. 

PMID- 24872317
TI  - RhoA/Rho kinase mediates TGF-beta1-induced kidney myofibroblast activation
      through Poldip2/Nox4-derived reactive oxygen species.
AB  - The small G proteins Rac1 and RhoA regulate actin cytoskeleton, cell shape,
      adhesion, migration, and proliferation. Recent studies in our laboratory have
      shown that NADPH oxidase Nox4-derived ROS are involved in transforming growth
      factor (TGF)-beta1-induced rat kidney myofibroblast differentiation assessed by
      the acquisition of an alpha-smooth muscle actin (alpha-SMA) phenotype and
      expression of an alternatively spliced fibronectin variant (Fn-EIIIA). Rac1 and
      RhoA are essential in signaling by some Nox homologs, but their role as effectors
      of Nox4 in kidney myofibroblast differentiation is not known. In the present
      study, we explored a link among Rac1 and RhoA and Nox4-dependent ROS generation
      in TGF-beta1-induced kidney myofibroblast activation. TGF-beta1 stimulated an
      increase in Nox4 protein expression, NADPH oxidase activity, and abundant alpha
      SMA and Fn-EIIIA expression. RhoA but not Rac1 was involved in TGF-beta1
      induction of Nox4 signaling of kidney myofibroblast activation. TGF-beta1
      stimulated active RhoA-GTP and increased Rho kinase (ROCK). Inhibition of RhoA
      with small interfering RNA and ROCK using Y-27632 significantly reduced TGF-beta1
      induced stimulation of Nox4 protein, NADPH oxidase activity, and alpha-SMA and Fn
      EIIIA expression. Treatment with diphenyleneiodonium, an inhibitor of NADPH
      oxidase, did not decrease RhoA activation but inhibited TGF-beta1-induced alpha
      SMA and Fn-EIIIA expression, indicating that RhoA is upstream of ROS generation.
      RhoA/ROCK also regulated polymerase (DNA-directed) delta-interacting protein 2
      (Poldip2), a newly discovered Nox4 enhancer protein. Collectively, these data
      indicate that RhoA/ROCK is upstream of Poldip2-dependent Nox4 regulation and ROS
      production and induces redox signaling of kidney myofibroblast activation and may
      broader implications in the pathophysiology of renal fibrosis. 

PMID- 24872320
TI  - The diabetic proximal tubule: part of the problem, and part of the solution?

PMID- 24872319
TI  - Effects of biomechanical forces on signaling in the cortical collecting duct
      (CCD).
AB  - An increase in tubular fluid flow rate (TFF) stimulates Na reabsorption and K
      secretion in the cortical collecting duct (CCD) and subjects cells therein to
      biomechanical forces including fluid shear stress (FSS) and circumferential
      stretch (CS). Intracellular MAPK and extracellular autocrine/paracrine PGE2
      signaling regulate cation transport in the CCD and, at least in other systems,
      are affected by biomechanical forces. We hypothesized that FSS and CS
      differentially affect MAPK signaling and PGE2 release to modulate cation
      transport in the CCD. To validate that CS is a physiological force in vivo, we
      applied the intravital microscopic approach to rodent kidneys in vivo to show
      that saline or furosemide injection led to a 46.5 +/- 2.0 or 170 +/- 32%
      increase, respectively, in distal tubular diameter. Next, murine CCD (mpkCCD)
      cells were grown on glass or silicone coated with collagen type IV and subjected
      to 0 or 0.4 dyne/cm(2) of FSS or 10% CS, respectively, forces chosen based on
      prior biomechanical modeling of ex vivo microperfused CCDs. Cells exposed to FSS
      expressed an approximately twofold greater abundance of phospho(p)-ERK and p-p38
      vs. static cells, while CS did not alter p-p38 and p-ERK expression compared with
      unstretched controls. FSS induced whereas CS reduced PGE2 release by ~40%. In
      conclusion, FSS and CS differentially affect ERK and p38 activation and PGE2
      release in a cell culture model of the CD. We speculate that TFF differentially
      regulates biomechanical signaling and, in turn, cation transport in the CCD. 

PMID- 24872321
TI  - The single midline implant in the edentulous mandible: a systematic review.
AB  - OBJECTIVES: The concept of a single midline implant retaining a complete
      mandibular denture is controversially discussed among experts. Studies are rare
      in the literature, and commonly accepted recommendations for this treatment
      options are not available. This systematic literature review was performed to
      give an overview over the current literature on the single midline implant
      therapy for the edentulous mandible and to reveal whether this treatment option
      might be an alternative to commonly accepted treatment modalities with more
      implants. METHODS: A review of the literature published until 24th of May 2013
      was conducted to identify in vivo studies on the single midline implant concept
      with a mean follow-up time of at least 3 months. RESULTS: From the electronic
      search, 11 studies were finally included. After an observation period of 3-60
      months, the implant survival rate ranged from 62.5 to 100 %. The most frequent
      prosthetic maintenance intervention was "activation of the matrix" followed by
      "repair of fractured denture base." CONCLUSIONS: The concept of one single
      midline implant to retain a mandibular complete denture can be an alternative,
      especially for elderly patients. Immediate loading of the implants should be
      avoided, and the way of integrating the matrix into the denture base should be
      carefully considered.

PMID- 24872322
TI  - Saliva substitutes in combination with high-fluoride gel on dentin
      remineralization.
AB  - OBJECTIVE: This study aimed to determine whether the application of a high
      fluoride gel could increase the remineralization of subsurface dentin lesions
      stored in saliva substitutes. MATERIALS AND METHODS: Demineralized bovine dentin
      specimens were stored in mineral water (W), Glandosane (G), or modified Saliva
      natura (SN). Different treatments were applied twice daily: no treatment, Elmex
      sensitive mouth rinse (E), ProSchmelz gel (P), Duraphat toothpaste (D), ED, PD,
      and EPD. Differences in mineral loss were evaluated by transversal
      microradiography after 2 and 5 weeks. RESULTS: The treatments with E, D, and ED
      inhibited the mineral loss induced by G and enabled some mineral gain. ProSchmelz
      was not able to inhibit the demineralizing effect of G. This high-fluoride gel
      induced an erosive mineral loss in combination with G. The use of ProSchmelz in
      combination or not with other fluoride products did not increase remineralization
      of specimens stored in SN or W (p > 0.05). ProSchmelz resulted in an erosion of
      the specimens stored in W and revealed a lower mineralized surface layer of
      specimens stored in SN. CONCLUSION: Topical application of high-fluoride gel
      reduced the mineral loss induced by G but resulted in an erosion of specimens'
      surface. In addition, ProSchmelz did not demonstrate beneficial effects in
      combination with SN on subsurface dentin lesion remineralization. CLINICAL
      RELEVANCE: Within the limitations of an in vitro study, it was concluded that the
      application of a high-fluoride gel did not promote additional effects on
      remineralization of subsurface dentin lesions in combination with saliva
      substitutes when compared to products with lower fluoride concentration.

PMID- 24872324
TI  - The influence of corporate structure and quality improvement activities on
      outcome improvement in residential care homes.
AB  - OBJECTIVE: To examine the impact of corporate structure and quality improvement
      (QI) activities on improvements in client-reported and professional indicators
      between 2007 and 2009. DESIGN: A cross-sectional study using organizational
      survey and indicator multilevel modelling to test relationships between corporate
      structure, QI activities and performance improvements on indicators. SETTING: In
      total, 169 residential care homes for the elderly in the Netherlands. MAIN
      OUTCOME MEASURES: Change between 2007 and 2009 in client-reported and
      professional indicators. RESULTS: A middle-size corporate structure was
      associated with QI. The QI activity 'multidisciplinary team meetings' was
      positively correlated with the indicator 'safety environment' for somatic and
      psycho-geriatric care. The QI activities 'educational material' and 'direct work
      instructions' were associated negatively with the indicator 'availability of
      personnel' for somatic clients, but positively for psycho-geriatric clients. QI
      activities such as 'health plan activities', 'clinical lessons' and 'financial
      activities' had no relationship to improved performance. For psycho-geriatric
      clients mainly organizational QI activities were positively associated with QI.
      The mediating role of the corporate structure for performing QI activities
      appeared stronger for the change in client-reported than for professional
      indicators. CONCLUSION: This study reveals associations between QI activities and
      corporate structure and changes in indicator performance. A corporate structure
      was associated with improvement in client-reported indicators, but less on
      professional indicators, which assumes a central policy at corporate level with
      impact on client-reported indicators, in contrast to a more local level approach
      towards activities that result in QI on professional indicators. Tailoring QI
      activities at the right managerial level may be important to achieve improvement.

PMID- 24872323
TI  - A quantitative HPLC-UV method for determination of serum sorafenib and sorafenib
      N-oxide and its application in hepatocarcinoma patients.
AB  - Sorafenib, an oral multi-kinase inhibitor, has been approved for treatment of
      advanced renal-cell and hepatocellular carcinoma (HCC). However, 20% of HCC
      patients taking sorafenib are forced to withdraw due to adverse effects within
      one month after administration. Orally administered sorafenib is oxidatively
      metabolized, predominantly by cytochrome P450 3A4 (CYP3A4), in small-intestinal
      mucosa or liver. We aimed to characterize the CYP3A4-mediated metabolism of
      sorafenib in HCC patients and explore the contribution of the major metabolite
      sorafenib N-oxide to adverse effects and therapeutic efficacy. We have therefore
      developed a method for quantitative determination of sorafenib and its N-oxide in
      the present study. To optimize the preanalytical procedure, we initially
      ascertained the solubility of the analytes. Because they are lipophilic, solvents
      containing more than 40% acetonitrile were required for efficient recovery. The
      pretreatment procedure that we ultimately developed consists of acetonitrile
      precipitation, followed by extraction using octadecyl silyl-silica gel to
      eliminate water-soluble and hydrophilic components of serum. Application of this
      procedure before HPLC enabled accurate and reproducible quantitation of analytes
      in a linear range from 0.03 to 30 MUg/mL. After characterizing the peaks in the
      HPLC-ultraviolet chromatogram obtained from a medicated patient by LC-tandem mass
      spectrometry, we applied this method to HCC patients taking sorafenib, showing
      large inter-individual differences in the pharmacokinetic profile. In conclusion,
      our assay system should be useful for follow-up of patients taking sorafenib and
      for exploring the association between the pharmacokinetics of sorafenib and its N
      oxide and the adverse effects or therapeutic efficacy. 

PMID- 24872325
TI  - Window of audio-visual simultaneity is unaffected by spatio-temporal visual
      clutter.
AB  - In the present study we investigate the rules governing the perception of
      audiovisual synchrony within spatio-temporally cluttered visual environments.
      Participants viewed a ring of 19 discs modulating in luminance while hearing an
      amplitude modulating tone. Each disc modulated with a unique temporal phase (40
      ms intervals), with only one synchronized to the tone. Participants searched for
      the synchronised disc whose spatial location varied randomly across trials.
      Square-wave modulation facilitated search: the synchronized disc was frequently
      chosen, with tight response distributions centred near zero-phase lag. In the
      sinusoidal condition responses were equally distributed over the 19 discs
      regardless of phase. To investigate whether subjective synchrony in the square
      wave condition was limited by spatial or temporal factors we repeated the
      experiment with either reduced spatial density (9 discs) or temporal density (80
      ms phase intervals). Reduced temporal density greatly facilitated synchrony
      perception but left the synchrony bandwidth unchanged, while no influence of
      spatial density was found. We conclude that audio-visual synchrony is not
      strongly constrained by the spatial or temporal density of the visual display,
      but by a temporal window within which audio-visual events are perceived as
      synchronous, with a full bandwidth of ~185 ms. 

PMID- 24872327
TI  - Ethics, "Vulnerability," and Feminist Participatory Action Research With a
      Disability Community.
AB  - We consider the work of research ethics boards and funding models for research
      that at times are incompatible with the relationship building required for
      feminist participatory action research with a disability community. We explore
      the barriers that emerged for university- and community-based partners as they
      asserted individual and collective identities, and negotiated boundaries, access,
      and power relations in the process of designing and conducting research. This
      critical reflection contributes to our understanding of the structures of
      academic research funding, ethics approval, and how problematic
      conceptualizations of vulnerability embedded in the Tri-Council Policy Statement
      and research ethics board practices impact on relationship building and the
      research process. Recommendations for change will be helpful to researchers
      studying disability, those using participatory action research, and individuals
      serving on ethics review boards.

PMID- 24872326
TI  - Cytotoxic markers associate with protection against malaria in human volunteers
      immunized with Plasmodium falciparum sporozoites.
AB  - BACKGROUND: Immunization of healthy volunteers by bites from Plasmodium
      falciparum-infected mosquitoes during chloroquine chemoprophylaxis (hereafter,
      chemoprophylaxis and sporozoites [CPS] immunization) induces sterile protection
      against malaria. CPS-induced protection is mediated by immunity against pre
      erythrocytic stages, presumably at least partially by cytotoxic cellular
      responses. We therefore aimed to investigate the association of CPS-induced
      cytotoxic T-cell markers with protection. METHODS: In a double-blind randomized
      controlled trial, we performed dose titration of CPS immunization followed by
      homologous challenge infection in 29 subjects. Immune responses were assessed by
      in vitro restimulation of peripheral blood mononuclear cells and flow cytometry.
      RESULTS: Dose-dependent complete protection was obtained in 4 of 5 volunteers
      after immunization with bites from 45 P. falciparum-infected mosquitoes, in 8 of
      9 volunteers with bites from 30, and in 5 of 10 volunteers with bites from 15
      (odds ratio [OR], 5.0; 95% confidence interval [CI], 1.5-17). Completely
      protected subjects had significantly higher proportions of CD4 T cells expressing
      the degranulation marker CD107a (OR, 8.4; 95% CI, 1.5-123; P = .011) and CD8
      cells producing granzyme B (OR, 11; 95% CI, 1.9-212; P = .004) after P.
      falciparum restimulation. CONCLUSIONS: These data underline the efficiency of CPS
      immunization to induce sterile protection and support a possible role for
      cytotoxic CD4 and CD8 T-cell responses in pre-erythrocytic immunity. CLINICAL
      TRIALS REGISTRATION: NCT01218893.

PMID- 24872328
TI  - Frequency of administration of erythropoiesis-stimulating agents for the anaemia
      of end-stage kidney disease in dialysis patients.
AB  - BACKGROUND: The benefits of erythropoiesis-stimulating agents (ESA) for dialysis
      patients have been demonstrated. However, it remains unclear whether the efficacy
      and safety of new, longer-acting ESA given less frequently is equivalent to
      recombinant human erythropoietin (rHuEPO) preparations. This is an update of a
      review first published in 2002 and last updated in 2005. OBJECTIVES: This review
      aimed to establish the optimal frequency of ESA administration in terms of
      effectiveness (correction of anaemia, and freedom from adverse events) and
      efficiency (optimal resource use) of different ESA dose regimens. SEARCH METHODS:
      We searched the Cochrane Renal Group's Specialised Register to 21 March 2013
      through contact with the Trials' Search Co-ordinator using search terms relevant
      to this review. SELECTION CRITERIA: We included randomised control trials (RCTs)
      comparing different frequencies of ESA administration in dialysis patients. DATA
      COLLECTION AND ANALYSIS: Two authors independently assessed study eligibility,
      risk of bias and extracted data. Results were expressed as risk ratio (RR) or
      risk differences (RD) with 95% confidence intervals (CI) for dichotomous
      outcomes. For continuous outcomes the mean difference (MD) or standardised mean
      difference (SMD) with 95% confidence intervals (CI) was used. Statistical
      analyses were performed using the random-effects model. MAIN RESULTS: This review
      included 33 studies (5526 participants), 22 of which were added for this update.
      Risk of bias was generally high; only nine studies were assessed at low risk of
      bias for sequence generation and 14 studies for allocation concealment. Although
      only four studies were placebo-controlled, all were considered to be at low risk
      of performance or detection bias because the primary outcome of haemoglobin level
      was a laboratory-derived assessment and unlikely to be influenced by lack of
      blinding. We found that 16 studies were at low risk of attrition bias and five
      were at low risk of selection bias; only one study reporting sources of support
      was not funded by a pharmaceutical company.We compared four different
      interventions: Continuous erythropoietin receptor agonists (CERA) versus other
      ESA (darbepoetin or rHuEPO); different frequencies of darbepoetin administration;
      darbepoetin versus rHuEPO; and different frequencies of rHuEPO
      administration.There were no significant differences in maintaining final
      haemoglobin between CERA administered at two weekly intervals (4 studies, 1762
      participants: MD 0.08 g/dL, 95% CI -0.04 to 0.21) or four weekly intervals (two
      studies, 1245 participants: MD -0.03 g/dL, 95% CI -0.17 to 0.12) compared with
      rHuEPO administered at two to three weekly intervals. In one study comparing CERA
      administered every two weeks with darbepoetin administered once/week, there was
      no significant difference in final haemoglobin (313 participants: MD 0.30 g/dL,
      95% CI 0.05 to 0.55). In comparisons of once/week with once every two weeks
      darbepoetin (two studies, 356 participants: MD 0.04 g/dL, 95% CI -0.45 to 0.52)
      and once every two weeks with monthly darbepoetin (one study, 64 participants: MD
      0.40 g/dL, 95% CI -0.37 to 1.17) there were no significant differences in final
      haemoglobin levels. There was marked heterogeneity among studies comparing weekly
      darbepoetin with once every two weeks and was possibly related to different
      administration protocols. Eight studies compared weekly darbepoetin with rHuEPO
      given two to three times/week; no statistical difference in final haemoglobin was
      demonstrated (6 studies, 1638 participants: MD 0.02 g/dL, 95% CI -0.09 to 0.12).
      Fourteen studies compared different frequencies of rHuEPO. No statistical
      difference was demonstrated in final haemoglobin (7 studies, 393 participants:
      SMD -0.17 g/dL, 95% CI -0.39 to 0.05). Adverse events did not differ
      significantly within comparisons; however, mortality and quality of life were
      poorly reported, particularly in earlier publications. AUTHORS' CONCLUSIONS:
      Longer-acting ESA (darbepoetin and CERA) administered at one to four week
      intervals are non-inferior to rHuEPO given one to three times/week in terms of
      achieving haemoglobin targets without any significant differences in adverse
      events in haemodialysis patients. Additional RCTs are required to evaluate
      different frequencies of ESA in peritoneal and paediatric dialysis patients and
      to compare different longer-acting ESA (such as darbepoetin compared with CERA).

PMID- 24872329
TI  - Robot-assisted single-incision total colectomy: a case report.
AB  - BACKGROUND: Literature reports shows that robots provide an opportunity for
      meeting technical challenges associated with Laparo-endoscopic Single Site
      Surgery (LESS). Following previous success with robot-assisted single-incision
      right hemicolectomy, this paper reports experience with robot-assisted single
      incision total colectomy. METHODS: Through a single incision around the
      umbilicus, three robotic ports and a laparoscopic port were placed through the
      GelPOINT. With one intraoperative redocking of the robot, it was possible to
      access both right and left sides of the colon. The entire colon was externalized
      through the GelPOINT and the umbilical incision closed in layers. RESULTS: The
      entire procedure took 227 minutes. There was minimal blood loss. The patient was
      discharged on post-operative day four with no complications. No wound site
      complications were observed in clinic one week after discharge. CONCLUSIONS:
      Robot-assisted single-incision total colectomy is a feasible procedure associated
      with little increase in operative time.

PMID- 24872331
TI  - Child health and the environment: where next with birth cohort research?

PMID- 24872332
TI  - Burden of reduced work productivity among people with chronic knee pain: a
      systematic review.
AB  - OBJECTIVE: The aims of this systematic review were to determine the prevalence of
      reduced work productivity among people with chronic knee pain as well as
      specifically categorise determinants of work productivity losses into individual,
      disease and work-related factors, conduct an evaluation of study methodological
      quality and present a best-evidence synthesis. METHODS: We searched the
      literature using combinations of key words such as knee pain, knee
      osteoarthritis, absenteeism (days taken off work) and presenteeism (reduced
      productivity while at work) for observational studies published in English.
      Methodological quality appraisal and a best-evidence synthesis were used to pool
      the study findings. RESULTS: The studies were conducted exclusively in high
      income countries of North America, Western Europe and Hong Kong. 17 studies were
      included in the review, 10 measuring absenteeism and six measuring presenteeism.
      Of the 10 studies reporting absenteeism, seven found a 12-month absenteeism
      prevalence ranging from 5% to 22%. Only two studies evaluated presenteeism
      prevalence and reported a range from 66% to 71%. Using best-evidence synthesis:
      three high quality cohort studies and three cross-sectional studies provided
      strong evidence that knee pain or knee osteoarthritis was associated with
      absenteeism; two high quality cross-sectional studies and one cohort study
      provided limited evidence for an association with presenteeism; one cross
      sectional study provided limited evidence for an association among age, high job
      demands and low coworker support and absenteeism among nurses with knee pain. No
      studies examined individual or work-related factors associated with presenteeism.
      CONCLUSIONS: A number of high quality studies consistently demonstrated that
      chronic knee pain or knee osteoarthritis is associated with absenteeism. However,
      data are lacking regarding presenteeism and individual or work-related risk
      factors for reduced work productivity among older workers with chronic knee pain.
      SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO registry number: CRD42013004137.

PMID- 24872335
TI  - An adolescent with abdominal pain, rash, joint swelling, severe bloody diarrhea,
      and impressive leukocytosis.

PMID- 24872333
TI  - Impact of treatment strategies on cephalosporin and tetracycline resistance gene
      quantities in the bovine fecal metagenome.
AB  - The study objective was to determine the effects of two treatment regimens on
      quantities of ceftiofur and tetracycline resistance genes in feedlot cattle. The
      two regimens were ceftiofur crystalline-free acid (CCFA) administered to either
      one or all steers within a pen and subsequent feeding/not feeding of therapeutic
      doses of chlortetracycline. A 26-day randomized controlled field trial was
      conducted on 176 steers. Real-time PCR was used to quantify bla(CMY-2), bla(CTX
      M), tet(A), tet(B), and 16S rRNA gene copies/gram of feces from community DNA. A
      significant increase in ceftiofur resistance and a decrease in tetracycline
      resistance elements were observed among the treatment groups in which all steers
      received CCFA treatment, expressed as gene copies/gram of feces. Subsequent
      chlortetracycline administration led to rapid expansion of both ceftiofur and
      tetracycline resistance gene copies/gram of feces. Our data suggest that
      chlortetracycline is contraindicated when attempting to avoid expansion of
      resistance to critically important third-generation cephalosporins.

PMID- 24872336
TI  - Atypical muscle spasms in an athletic adolescent.

PMID- 24872334
TI  - Prenatal exposure to hypoxia induced Beclin 1 signaling-mediated renal autophagy
      and altered renal development in rat fetuses.
AB  - AIMS: Hypoxia has adverse effects on renal development. This study was the first
      to test hypoxia-induced renal autophagy in rat fetuses. METHODS: Pregnant rats
      were exposed to hypoxia or normoxia during pregnancy and fetal kidneys were
      collected at gestation day 21. RESULTS: Fetal kidney weight and ratio of kidney
      body weight were reduced. Histological analysis showed enlargement in Bowman
      space and wider space between interstitia in the kidneys of fetus exposed to
      hypoxia. Fetal renal B-cell lymphoma 2 (BCL-2) was decreased accompanied with
      higher 2'-deoxyuridine 5'-triphosphate nick end-labeling staining and unchanged
      soluble FAS in the hypoxia group. Hypoxia increased autophagic structures,
      including autophagosomes and autolysosomes, in fetal kidneys and increased renal
      APG5L. There was an increase in renal LC3-II, Beclin 1, p-S6, hypoxia inducible
      factor 1alpha (HIF-1a), and ratio of LC3-II-LC3-I and a decrease in P62, protein
      kinase B (AKT), and phosphorylated AKT in the hypoxia group. Both renal mammalian
      target of rapamycin (mTOR) and Beclin 1 signaling were upregulated. CONCLUSION:
      Hypoxia-affected fetal renal development was associated with renal apoptosis and
      Beclin 1 signaling-mediated autophagy.

PMID- 24872337
TI  - Pediatrician noncompliance with the American Academy of Pediatrics guidelines for
      the workup of UTI in infants.
AB  - BACKGROUND: The American Academy of Pediatrics (AAP) guidelines on the workup for
      urinary tract infections (UTIs) in infants discourages the use of bagged urine
      specimens for urine culture. We report the results of a survey to assess urine
      collection preferences and adherence to AAP guidelines in clinical practice.
      METHODS: A 29-question survey was e-mailed to pediatrician AAP members to
      determine their preferred method of urine collection in hypothetical infant
      patients. RESULTS: Data from 155 respondents were analyzed. In febrile,
      circumcised boys, up to 18% preferred bagged specimens for urine culture, against
      AAP recommendations. In febrile girls, 13% of respondents preferred bagged
      specimens. There was no significant relationship between adherence to AAP
      guidelines and respondent's age, gender, years in practice, fellowship training,
      academic affiliation, or other demographic factors. CONCLUSIONS: Up to 18% of
      practitioners prefer bagged specimens over more sterile ones in the workup of
      febrile UTIs in infants, against AAP guidelines.

PMID- 24872338
TI  - Parental risk for the maltreatment of developmentally delayed/disabled children.

PMID- 24872339
TI  - Metabolic bone disease screening practices among U.S. neonatologists.
AB  - Preterm, low-birth-weight neonates are predisposed to metabolic bone disease
      (MBD). This survey aimed to assess screening, diagnostic, and treatment practices
      in U.S. level IIIB/IIIC neonatal intensive care units (NICUs). A 29-question
      anonymous online survey was e-mailed to American Academy of Pediatrics Perinatal
      Section members. 338 neonatologists, representing 246 IIIB/IIIC NICUs, responded.
      86% reported MBD screening. Screening was primarily based on gestational age
      (71%), with thresholds <26 to <36 weeks. Other criteria included birth weight
      (64%), total parenteral nutrition duration (48%), X-ray findings (56%), diuretic
      use (41%), and exclusive breast-feeding (9.6%). Almost universally, diagnosis was
      based on elevated alkaline phosphatase, most commonly >500 U/L (58.6%). 52% used
      X-ray for diagnosis. Treatment included human milk fortification (83%), vitamin D
      (67%), calcium (65%), and phosphorus (65%) supplementation. Our survey confirms
      widespread awareness of MBD but highlights lack of consensus regarding
      definition, screening, and treatment. Further research is needed to develop and
      optimize strategies to prevent, recognize, and manage MBD.

PMID- 24872340
TI  - NekNominate: a deadly, social media-based drinking dare.

PMID- 24872342
TI  - Evaluating and classifying the readiness of technology specifications for
      national standardization.
AB  - The American Recovery and Reinvestment Act (ARRA) of 2009 clearly articulated the
      central role that health information technology (HIT) standards would play in
      improving healthcare quality, safety, and efficiency through the meaningful use
      of certified, standards based, electronic health record (EHR) technology. In
      2012, the Office of the National Coordinator (ONC) asked the Nationwide Health
      Information Network (NwHIN) Power Team of the Health Information Technology
      Standards Committee (HITSC) to develop comprehensive, objective, and, to the
      extent practical, quantitative criteria for evaluating technical standards and
      implementation specifications and classifying their readiness for national
      adoption. The Power Team defined criteria, attributes, and metrics for evaluating
      and classifying technical standards and specifications as 'emerging,' 'pilot,' or
      'ready for national standardization' based on their maturity and adoptability.
      The ONC and the HITSC are now using these metrics for assessing the readiness of
      technical standards for national adoption. 

PMID- 24872343
TI  - Bringing science to medicine: an interview with Larry Weed, inventor of the
      problem-oriented medical record.
AB  - Larry Weed, MD is widely known as the father of the problem-oriented medical
      record and inventor of the now-ubiquitous SOAP
      (subjective/objective/assessment/plan) note, for developing an electronic health
      record system (Problem-Oriented Medical Information System, PROMIS), and for
      founding a company (since acquired), which developed problem-knowledge couplers.
      However, Dr Weed's vision for medicine goes far beyond software--over the course
      of his storied career, he has relentlessly sought to bring the scientific method
      to medical practice and, where necessary, to point out shortcomings in the system
      and advocate for change. In this oral history, Dr Weed describes, in his own
      words, the arcs of his long career and the work that remains to be done.

PMID- 24872344
TI  - Viruses versus bacteria-novel approaches to phage therapy as a tool against
      multidrug-resistant pathogens.
AB  - Bacteriophage therapy (the application of phages to treat bacterial infections)
      has a tradition dating back almost a century, but interest in phage therapy
      slowed down in the West when antibiotics were discovered. With the emerging
      threat of infections caused by multidrug-resistant bacteria and scarce prospects
      of newly introduced antibiotics in the future, phages are currently being
      reconsidered as alternative therapeutics. Conventional phage therapy uses lytic
      bacteriophages for treatment and recent human clinical trials have revealed
      encouraging results. In addition, several other modern approaches to phages as
      therapeutics have been made in vitro and in animal models. Dual therapy with
      phages and antibiotics has resulted in significant reductions in the number of
      bacterial pathogens. Bioengineered phages have overcome many of the problems of
      conventional phage therapy, enabled targeted drug delivery or reversed the
      resistance of drug-resistant bacteria. The use of enzymes derived from phages,
      such as endolysin, as therapeutic agents has been efficient in the elimination of
      Gram-positive pathogens. This review presents novel strategies for phage-related
      therapies and describes our current knowledge of natural bacteriophages within
      the human microbiome. Our aim is to provide an overview of the high number of
      different methodological concepts, thereby encouraging further research on this
      topic, with the ultimate goal of using phages as therapeutic or preventative
      medicines in daily clinical practice. 

PMID- 24872341
TI  - Effects of librarian-provided services in healthcare settings: a systematic
      review.
AB  - OBJECTIVE: To assess the effects of librarian-provided services in healthcare
      settings on patient, healthcare provider, and researcher outcomes. MATERIALS AND
      METHODS: Medline, CINAHL, ERIC, LISA (Library and Information Science Abstracts),
      and the Cochrane Central Register of Controlled Trials were searched from
      inception to June 2013. Studies involving librarian-provided services for
      patients encountering the healthcare system, healthcare providers, or researchers
      were eligible for inclusion. All librarian-provided services in healthcare
      settings were considered as an intervention, including hospitals, primary care
      settings, or public health clinics. RESULTS: Twenty-five articles fulfilled our
      eligibility criteria, including 22 primary publications and three companion
      reports. The majority of studies (15/22 primary publications) examined librarians
      providing instruction in literature searching to healthcare trainees, and
      measured literature searching proficiency. Other studies analyzed librarian
      provided literature searching services and instruction in question formulation as
      well as the impact of librarian-provided services on patient length of stay in
      hospital. No studies were found that investigated librarians providing direct
      services to researchers or patients in healthcare settings. CONCLUSIONS:
      Librarian-provided services directed to participants in training programs (eg,
      students, residents) improve skills in searching the literature to facilitate the
      integration of research evidence into clinical decision-making. Services provided
      to clinicians were shown to be effective in saving time for health professionals
      and providing relevant information for decision-making. Two studies indicated
      patient length of stay was reduced when clinicians requested literature searches
      related to a patient's case.

PMID- 24872345
TI  - Once-daily dosed gentamicin is more nephrotoxic than once-daily dosed tobramycin
      in clinically infected patients.

PMID- 24872346
TI  - Combination therapy for carbapenem-resistant Gram-negative bacteria.
AB  - Carbapenem-resistant Gram-negative bacteria (CR-GNB) represent an increasing
      hazard in healthcare settings. A central question concerning the treatment of
      invasive infections caused by CR-GNB involves the use of combination therapy.
      Potential advantages of combination therapy include improved efficacy due to
      synergy, while the disadvantages include adverse events and increased antibiotic
      use with a potential drive towards resistance. Several observational studies have
      examined whether combination therapy offers an advantage over colistin/polymyxin
      monotherapy. We highlight the inherent limitations of these studies related to
      their observational design and sample size to show why they do not at present
      provide an answer to the question of combination versus monotherapy. This
      distinction is important to guide clinical practice until solid evidence has been
      obtained and to enable the recruitment of patients into randomized controlled
      trials. A few randomized controlled trials examining specific combinations have
      recently been completed or are ongoing. Currently, however, there is no evidence
      based support for most combination therapies against CR-GNB, including
      colistin/carbapenem combination therapy. 

PMID- 24872347
TI  - Adverse Childhood Experiences in the Lives of Male Sex Offenders: Implications
      for Trauma-Informed Care.
AB  - This study explored the prevalence of childhood trauma in a sample of male sexual
      offenders (N = 679) using the Adverse Childhood Experience (ACE) scale. Compared
      with males in the general population, sex offenders had more than 3 times the
      odds of child sexual abuse (CSA), nearly twice the odds of physical abuse, 13
      times the odds of verbal abuse, and more than 4 times the odds of emotional
      neglect and coming from a broken home. Less than 16% endorsed zero ACEs and
      nearly half endorsed four or more. Multiple maltreatments often co-occurred with
      other types of household dysfunction, suggesting that many sex offenders were
      raised within a disordered social environment. Higher ACE scores were associated
      with higher risk scores. By enhancing our understanding of the frequency and
      correlates of early adverse experiences, we can better devise trauma-informed
      interventions that respond to the clinical needs of sex offender clients. 

PMID- 24872348
TI  - Calcium channel blockers in cardiovascular pharmacotherapy.
AB  - This paper summarizes the pharmacological properties of calcium channel blockers
      (CCBs), their established therapeutic uses for cardiovascular disorders and the
      current improvement of their clinical effects through drug combinations. Their
      identification resulted from study of small molecules including coronary
      dilators, which were named calcium antagonists. Further experiments showed that
      they reduced contraction of arteries by inhibiting calcium entry and by
      interacting with binding sites identified on voltage-dependent calcium channels.
      This led to the denomination calcium channel blockers. In short-term studies, by
      decreasing total peripheral resistance, CCBs lower arterial pressure. By
      unloading the heart and increasing coronary blood flow, CCBs improve myocardial
      oxygenation. In long-term treatment, the decrease in blood pressure is more
      pronounced in hypertensive than in normotensive patients. A controversy on the
      safety of CCBs ended after a large antihypertensive trial (ALLHAT) sponsored by
      the National Heart, Lung, and Blood Institute. There are two main types of CCBs:
      dihydopyridine and non-dihydropyridine; the first type is vascular selective.
      Dihydropyrines are indicated for hypertension, chronic, stable and vasospastic
      angina. Non-dihydropyridines have the same indications plus antiarrythmic effects
      in atrial fibrillation or flutter and paroxysmal supraventricular tachycardia. In
      addition, CCBs reduced newly formed coronary lesions in atherosclerosis. In order
      to reach recommended blood pressure goals, there is a recent therapeutic move by
      combination of CCBs with other antihypertensive agents particularly with
      inhibitors acting at the level of the renin-angiotensin system. They are also
      combined with statins. Prevention of dementia has been reported in hypertensive
      patients treated with nitrendipine, opening a way for further studies on CCBs'
      beneficial effect in cognitive deterioration associated with aging. 

PMID- 24872349
TI  - Cardiovascular disease risk in childhood cancer survivors.

PMID- 24872351
TI  - Employment arrangements and mental health in a cohort of working Australians: are
      transitions from permanent to temporary employment associated with changes in
      mental health?
AB  - We investigated whether being in temporary employment, as compared with permanent
      employment, was associated with a difference in Short Form 36 mental health and
      whether transitions from permanent employment to temporary employment were
      associated with mental health changes. We used fixed-effects regression in a
      nationally representative Australian sample with 10 waves of data collection
      (2001-2010). Interactions by age and sex were tested. Two forms of temporary
      employment were studied: "casual" (no paid leave entitlements or fixed hours) and
      "fixed-term contract" (a defined employment period plus paid leave). There were
      no significant mental health differences between temporary employment and
      permanent employment in standard fixed-effects analyses and no significant
      interactions by sex or age. For all age groups combined, there were no
      significant changes in mental health following transitions from stable permanent
      employment to temporary employment, but there was a significant interaction with
      age (P = 0.03) for the stable-permanent-to-casual employment transition, because
      of a small transition-associated improvement in mental health for workers aged 55
      64 years (beta = 1.61, 95% confidence interval: 0.34, 2.87; 16% of the standard
      deviation of mental health scores). Our analyses suggest that temporary
      employment is not harmful to mental health in the Australian context and that it
      may be beneficial for 55- to 64-year-olds transitioning from stable permanent
      employment to casual employment.

PMID- 24872352
TI  - Fully non-parametric receiver operating characteristic curve estimation for
      random-effects meta-analysis.
AB  - Meta-analyses, broadly defined as the quantitative review and synthesis of the
      results of related but independent comparable studies, allow to know the state of
      the art of one considered topic. Since the amount of available bibliography has
      enhanced in almost all fields and, specifically, in biomedical research, its
      popularity has drastically increased during the last decades. In particular,
      different methodologies have been developed in order to perform meta-analytic
      studies of diagnostic tests for both fixed- and random-effects models. From a
      parametric point of view, these techniques often compute a bivariate estimation
      for the sensitivity and the specificity by using only one threshold per included
      study. Frequently, an overall receiver operating characteristic curve based on a
      bivariate normal distribution is also provided. In this work, the author deals
      with the problem of estimating an overall receiver operating characteristic curve
      from a fully non-parametric approach when the data come from a meta-analysis
      study i.e. only certain information about the diagnostic capacity is available.
      Both fixed- and random-effects models are considered. In addition, the proposed
      methodology lets to use the information of all cut-off points available (not only
      one of them) in the selected original studies. The performance of the method is
      explored through Monte Carlo simulations. The observed results suggest that the
      proposed estimator is better than the reference one when the reported information
      is related to a threshold based on the Youden index and when information for two
      or more points are provided. Real data illustrations are included.

PMID- 24872354
TI  - BLX-1002 restores glucose sensitivity and enhances insulin secretion stimulated
      by GLP-1 and sulfonylurea in type 2 diabetic pancreatic islets.
AB  - BLX-1002 is a novel thiazolidinedione with no peroxisome proliferator-activated
      receptor (PPAR) activity that has been shown to improve glycemia in type 2
      diabetes without weight gain. We previously found that BLX-1002 selectively
      augments glucose-sensitive (but not basal) insulin secretion in normal mouse beta
      cells. We have now extended these observations to other insulin secretagogues and
      to diabetic rat islets. To this end, dynamics of insulin secretion stimulated by
      glucose, GLP-1, and the sulfonylurea tolbutamide were examined in pancreatic
      islets from nondiabetic Wistar and type 2 diabetic Goto-Kakizaki rats ex vivo.
      BLX-1002 restored normal glucose-sensitive insulin secretion in otherwise
      "glucose-blind" islets from GK rats, but did not affect basal or glucose
      stimulated secretion in normal Wistar rat islets. The stimulatory effect of BLX
      1002 on insulin secretion at high glucose required Ca(2+) and involved
      phosphatidylinositol 3-kinase (PI3K) activity. Consistent with its effects on
      insulin secretion, BLX-1002 also augmented insulin secretion and cytoplasmic-free
      Ca(2+) concentrations ([Ca(2+)]i) stimulated by high glucose, GLP-1, and
      tolbutamide in islets from GK, but not Wistar, rats. The inactive analog BLX-1237
      had no effects. In conclusion, our findings suggest that BLX-1002 potentiates
      insulin secretion by different stimuli in diabetic beta-cells only, in a Ca(2+)
      dependent manner and involving PI3K. 

PMID- 24872353
TI  - Meta-analysis of the technical performance of an imaging procedure: guidelines
      and statistical methodology.
AB  - Medical imaging serves many roles in patient care and the drug approval process,
      including assessing treatment response and guiding treatment decisions. These
      roles often involve a quantitative imaging biomarker, an objectively measured
      characteristic of the underlying anatomic structure or biochemical process
      derived from medical images. Before a quantitative imaging biomarker is accepted
      for use in such roles, the imaging procedure to acquire it must undergo
      evaluation of its technical performance, which entails assessment of performance
      metrics such as repeatability and reproducibility of the quantitative imaging
      biomarker. Ideally, this evaluation will involve quantitative summaries of
      results from multiple studies to overcome limitations due to the typically small
      sample sizes of technical performance studies and/or to include a broader range
      of clinical settings and patient populations. This paper is a review of meta
      analysis procedures for such an evaluation, including identification of suitable
      studies, statistical methodology to evaluate and summarize the performance
      metrics, and complete and transparent reporting of the results. This review
      addresses challenges typical of meta-analyses of technical performance,
      particularly small study sizes, which often causes violations of assumptions
      underlying standard meta-analysis techniques. Alternative approaches to address
      these difficulties are also presented; simulation studies indicate that they
      outperform standard techniques when some studies are small. The meta-analysis
      procedures presented are also applied to actual [18F]-fluorodeoxyglucose positron
      emission tomography (FDG-PET) test-retest repeatability data for illustrative
      purposes. 

PMID- 24872355
TI  - Age-related remodeling of small arteries is accompanied by increased
      sphingomyelinase activity and accumulation of long-chain ceramides.
AB  - The structure and function of large arteries alters with age leading to increased
      risk of cardiovascular disease. Age-related large artery remodeling and
      arteriosclerosis is associated with increased collagen deposition, inflammation,
      and endothelial dysfunction. Bioactive sphingolipids are known to regulate these
      processes, and are also involved in aging and cellular senescence. However, less
      is known about age-associated alterations in small artery morphology and function
      or whether changes in arterial sphingolipids occur in aging. We show that
      mesenteric small arteries from old sheep have increased lumen diameter and media
      thickness without a change in media to lumen ratio, indicative of outward
      hypertrophic remodeling. This remodeling occurred without overt changes in blood
      pressure or pulse pressure indicating it was a consequence of aging per se. There
      was no age-associated change in mechanical properties of the arteries despite an
      increase in total collagen content and deposition of collagen in a thickened
      intima layer in arteries from old animals. Analysis of the sphingolipid profile
      showed an increase in long-chain ceramide (C14-C20), but no change in the levels
      of sphingosine or sphingosine-1-phosphate in arteries from old compared to young
      animals. This was accompanied by a parallel increase in acid and neutral
      sphingomyelinase activity in old arteries compared to young. This study
      demonstrates remodeling of small arteries during aging that is accompanied by
      accumulation of long-chain ceramides. This suggests that sphingolipids may be
      important mediators of vascular aging. 

PMID- 24872356
TI  - Estrogen increases ENaC activity via PKCdelta signaling in renal cortical
      collecting duct cells.
AB  - The most active estrogen, 17beta-estradiol (E2), has previously been shown to
      stimulate a female sex-specific antisecretory response in the intestine. This
      effect is thought to contribute to the increase in whole body extracellular fluid
      (ECF) volume which occurs in high estrogen states, such as in the implantation
      window during estrous cycle. The increased ECF volume may be short-circuited by a
      renal compensation unless estrogen exerts a proabsorptive effect in the nephron.
      Thus, the effect of E2 on ENaC in kidney cortical collecting duct (CCD) cells is
      of interest to understand estrogen regulation of ECF volume. Previous studies
      showed a rapid stimulatory effect of estrogen on ENaC in bronchial epithelium. In
      this study we examined if such a rapid effect on Na(+) absorption could occur in
      the kidney. Experiments were carried out on murine M1-CCD cell cultures. E2 (25
      nmol/L) treatment caused a rapid-onset (<15 min) and sustained increase in the
      amiloride-sensitive Na(+) current (INa) in CCD monolayers mounted in Ussing
      chambers (control, 1.9 +/- 0.2 MUA/cm(2); E2, 4.7 +/- 0.3 MUA/cm(2); n = 43, P <
      0.001), without affecting the ouabain-sensitive Na(+)/K(+) pump current. The INa
      response to E2 was inhibited by PKCdelta activity antagonism with rottlerin (5
      MUmol/L), inhibition of matrix metalloproteinases activity with GM6001 (1
      MUmol/L), inhibition of EGFR activity with AG1478 (10 MUmol/L), inhibition of PLC
      activity with U-73122 (10 MUmol/L), and inhibition of estrogen receptors with the
      general ER antagonist ICI-182780 (100 nmol/L). The estrogen activation of INa
      could be mimicked by the ERalpha agonist PPT (1 nmol/L). The nuclear excluded
      estrogen dendrimer conjugate (EDC) induced similar stimulatory effects on INa
      comparable to free E2. The end target for E2 stimulation of PKCdelta was shown to
      be an increased abundance of the gamma-ENaC subunit in the apical plasma membrane
      of CCD cells. We have demonstrated a novel rapid "nongenomic" function of
      estrogen to stimulate ENaC via ERalpha-EGFR transactivation in kidney CCD cells.
      We propose that the salt-retaining effect of estrogen in the kidney together with
      its antisecretory action in the intestine are the molecular mechanisms causing
      the expanded ECF volume in high-estrogen states. 

PMID- 24872350
TI  - Who is more affected by ozone pollution? A systematic review and meta-analysis.
AB  - Ozone is associated with adverse health; however, less is known about
      vulnerable/sensitive populations, which we refer to as sensitive populations. We
      systematically reviewed epidemiologic evidence (1988-2013) regarding sensitivity
      to mortality or hospital admission from short-term ozone exposure. We performed
      meta-analysis for overall associations by age and sex; assessed publication bias;
      and qualitatively assessed sensitivity to socioeconomic indicators,
      race/ethnicity, and air conditioning. The search identified 2,091 unique papers,
      with 167 meeting inclusion criteria (73 on mortality and 96 on hospitalizations
      and emergency department visits, including 2 examining both mortality and
      hospitalizations). The strongest evidence for ozone sensitivity was for age. Per
      10-parts per billion increase in daily 8-hour ozone concentration, mortality risk
      for younger persons, at 0.60% (95% confidence interval (CI): 0.40, 0.80), was
      statistically lower than that for older persons, at 1.27% (95% CI: 0.76, 1.78).
      Findings adjusted for publication bias were similar. Limited/suggestive evidence
      was found for higher associations among women; mortality risks were 0.39% (95%
      CI: -0.22, 1.00) higher than those for men. We identified strong evidence for
      higher associations with unemployment or lower occupational status and weak
      evidence of sensitivity for racial/ethnic minorities and persons with low
      education, in poverty, or without central air conditioning. Findings show that
      some populations, especially the elderly, are particularly sensitive to short
      term ozone exposure. 

PMID- 24872358
TI  - Angiotensin receptors modulate the renal hemodynamic effects of nitric oxide in
      conscious newborn lambs.
AB  - This study aimed to elucidate the roles of both angiotensin II (ANG II) receptors
      - type 1 (AT1Rs) and type 2 (AT2Rs) - separately and together in influencing
      hemodynamic effects of endogenously produced nitric oxide (NO) during postnatal
      development. In conscious, chronically instrumented lambs aged ~1 week (8 +/- 1
      days, N = 8) and ~6 weeks (41 +/- 2 days, N = 8), systolic, diastolic, and mean
      arterial pressure (SAP, DAP, MAP) and venous pressure (MVP), renal blood flow
      (RBF), and renal vascular resistance (RVR) were measured in response to the l
      arginine analog, l-NAME after pretreatment with either the AT1R antagonist, ZD
      7155, the AT2R antagonist, PD 123319, or both antagonists. The increase in SAP,
      DAP, and MAP by l-NAME was not altered by either ATR antagonist in either age
      group. The increase in RBF after l-NAME was, however, altered by both ATR
      antagonists in an age-dependent manner, which was mediated predominantly through
      AT2Rs in newborn lambs. These findings reveal that there is an age-dependent
      interaction between the renin-angiotensin (RAS) and the NO pathway in regulating
      renal but not systemic hemodynamics through both ATRs, whereas AT2Rs appear to be
      important in the renal hemodynamic effects of NO early in life. 

PMID- 24872360
TI  - Dose-finding studies, MCP-Mod, model selection, and model averaging: Two
      applications in the real world.
AB  - BACKGROUND: Phase II clinical trials are important milestones to determine
      whether a dose-effect exists and to decide on future doses to use in confirmatory
      studies. To take into account the overall shape of the dose-response curve,
      modeling the relationship by linear or non-linear models is preferable to the
      classical pair-wise comparisons of the effect of each dose versus the placebo or
      the comparator. The multiple comparisons and modeling approach has been developed
      within the last 10 years to address this important question in the clinical
      development of drugs. Despite some recent publications referring to this
      methodology, few detailed applications have been shown so far and several
      practical questions remain to be addressed. METHODS: Starting from a set of
      candidate models, model selection using classical methods criteria is possible.
      However, it suffers some limitations, not taking into account the uncertainty of
      the selection process itself. An attractive solution is to use model averaging,
      which applies appropriate weights to the parameters (e.g., the minimum effective
      dose) obtained from each model. RESULTS: A discussion of the selection criteria
      is first presented. Through two real examples, how to proceed with model
      selection and model averaging is presented and discussed. LIMITATIONS: The first
      multiple comparisons and modeling approach papers addressed normal responses.
      More recently, an extension of this methodology has been proposed to deal with
      other types of responses, in particular binary, time-to-event and longitudinal
      data. Questions that remain are concerned with the choice of the candidate models
      and of their parameters' guesstimates. CONCLUSIONS: The analysis of clinical dose
      finding studies using a modeling of the entire curve offers a promising
      alternative as compared with the classical multiple comparisons methods, while
      not compromising the necessary rigor of the analysis.

PMID- 24872357
TI  - Maternal nicotinic exposure produces a depressed hypoxic ventilatory response and
      subsequent death in postnatal rats.
AB  - In this study, we asked whether a "full term" prenatal nicotinic exposure (fPNE,
      6 mg.kg(-1).day(-1) nicotinic delivery) over the full gestation, compared to a
      traditional PNE (tPNE) over the last two-thirds of the gestation, caused a higher
      mortality following a remarkable depressed hypoxic ventilatory response (dHVR)
      independent of brain and pulmonary edema and change in serum corticosterone. P12
      14 pups pretreated with tPNE, fPNE or their vehicle (tCtrl and fCtrl) were
      exposed to 5% O2 for up to 60 min followed by harvesting the brain and lungs or
      anesthetized to collect blood for detecting arterial blood pH/gases and serum
      cotinine and corticosterone levels. We found that fPNE had little effect on
      baseline VE and heart rate, but consistently induced a dHVR and prolonged apnea
      that were rarely observed after tPNE. The severity of the dHVR in PNE pups were
      closely correlated to an earlier appearance of lethal ventilatory arrest (the
      hypoxia-induced mortality). PNE did not induce brain and pulmonary edema, but
      significantly increased serum corticosterone levels similarly in tPNE and fPNE
      pups. Moreover, the accumulated nicotinic dose given to the individual was
      significantly higher in fPNE than tPNE pups, though there was no difference in
      serum cotinine levels and arterial blood pH/gases between the two groups. Our
      results suggest that nicotinic exposure at the early stage of gestation achieved
      by fPNE, rather than tPNE, is critical in generating the dHVR and subsequent
      death occurring independently of brain/pulmonary edema and changes in arterial
      blood pH/gases and serum corticosterone. 

PMID- 24872359
TI  - Guanosine regulates adenosine levels in the kidney.
AB  - In cell culture, extracellular guanosine increases extracellular adenosine by
      attenuating the disposition of extracellular adenosine (American Journal of
      Physiology - Cell Physiology 304: C406-C421, 2013). The goal of this
      investigation was to determine whether this "guanosine-adenosine mechanism" is
      operative in an intact organ. Twenty-seven isolated, perfused mouse kidneys were
      subjected to metabolic poisons (iodoacetate plus 2,4-dinitrophenol) to cause
      energy depletion and thereby stimulate renal adenosine production. Adenosine
      levels in the renal venous perfusate increased from a baseline of 36 +/- 8 to 499
      +/- 96, 258 +/- 50, and 71 +/- 13 nmol/L at 15, 30, and 60 min, respectively,
      after administering metabolic poisons (% of basal; 1366 +/- 229, 715 +/- 128, and
      206 +/- 33, respectively). Changes in renal venous levels of guanosine closely
      mirrored the time course of changes in adenosine: baseline of 15 +/- 2 to 157 +/-
      13, 121 +/- 8, and 50 +/- 5 nmol/L at 15, 30, and 60 min, respectively (% of
      basal; 1132 +/- 104, 871 +/- 59, and 400 +/- 51, respectively). Freeze-clamp
      experiments in 12 kidneys confirmed that metabolic poisons increased kidney
      tissue levels of adenosine and guanosine. In eight additional kidneys, we
      examined the ability of guanosine to reduce the renal clearance of exogenous
      adenosine; and these experiments revealed that guanosine significantly decreased
      the renal extraction of adenosine. Because guanosine is metabolized by purine
      nucleoside phosphorylase (PNPase), in another set of 16 kidneys we examined the
      effects of 8-aminoguanine (PNPase inhibitor) on renal venous levels of adenosine
      and inosine (adenosine metabolite). Kidneys treated with 8-aminoguanine showed a
      more robust increase in both adenosine and inosine in response to metabolic
      poisons. We conclude that in the intact kidney, guanosine regulates adenosine
      levels. 

PMID- 24872361
TI  - Estimation of optimal dynamic treatment regimes.
AB  - BACKGROUND: Recent advances in medical research suggest that the optimal
      treatment rules should be adaptive to patients over time. This has led to an
      increasing interest in studying dynamic treatment regime, a sequence of
      individualized treatment rules, one per stage of clinical intervention, which
      maps present patient information to a recommended treatment. There has been a
      recent surge of statistical work for estimating optimal dynamic treatment regimes
      from randomized and observational studies. The purpose of this article is to
      review recent methodological progress and applied issues associated with
      estimating optimal dynamic treatment regimes. METHODS: We discuss sequential
      multiple assignment randomized trials, a clinical trial design used to study
      treatment sequences. We use a common estimator of an optimal dynamic treatment
      regime that applies to sequential multiple assignment randomized trials data as a
      platform to discuss several practical and methodological issues. RESULTS: We
      provide a limited survey of practical issues associated with modeling sequential
      multiple assignment randomized trials data. We review some existing estimators of
      optimal dynamic treatment regimes and discuss practical issues associated with
      these methods including model building, missing data, statistical inference, and
      choosing an outcome when only non-responders are re-randomized. We mainly focus
      on the estimation and inference of dynamic treatment regimes using sequential
      multiple assignment randomized trials data. Dynamic treatment regimes can also be
      constructed from observational data, which may be easier to obtain in practice;
      however, care must be taken to account for potential confounding.

PMID- 24872362
TI  - A novel application of the Intent to Attend assessment to reduce bias due to
      missing data in a randomized controlled clinical trial.
AB  - BACKGROUND: Missing data are unavoidable in most randomized controlled clinical
      trials, especially when measurements are taken repeatedly. If strong assumptions
      about the missing data are not accurate, crude statistical analyses are biased
      and can lead to false inferences. Furthermore, if we fail to measure all
      predictors of missing data, we may not be able to model the missing data process
      sufficiently. In longitudinal randomized trials, measuring a patient's intent to
      attend future study visits may help to address both of these problems. Leon et
      al. developed and included the Intent to Attend assessment in the Lithium
      Treatment - Moderate dose Use Study (LiTMUS), aiming to remove bias due to
      missing data from the primary study hypothesis. PURPOSE: The purpose of this
      study is to assess the performance of the Intent to Attend assessment with regard
      to its use in a sensitivity analysis of missing data. METHODS: We fit marginal
      models to assess whether a patient's self-rated intent predicted actual study
      adherence. We applied inverse probability of attrition weighting (IPAW) coupled
      with patient intent to assess whether there existed treatment group differences
      in response over time. We compared the IPAW results to those obtained using other
      methods. RESULTS: Patient-rated intent predicted missed study visits, even when
      adjusting for other predictors of missing data. On average, the hazard of
      retention increased by 19% for every one-point increase in intent. We also found
      that more severe mania, male gender, and a previously missed visit predicted
      subsequent absence. Although we found no difference in response between the
      randomized treatment groups, IPAW increased the estimated group difference over
      time. LIMITATIONS: LiTMUS was designed to limit missed study visits, which may
      have attenuated the effects of adjusting for missing data. Additionally, IPAW can
      be less efficient and less powerful than maximum likelihood or Bayesian
      estimators, given that the parametric model is well specified. CONCLUSIONS: In
      LiTMUS, the Intent to Attend assessment predicted missed study visits. This item
      was incorporated into our IPAW models and helped reduce bias due to informative
      missing data. This analysis should both encourage and facilitate future use of
      the Intent to Attend assessment along with IPAW to address missing data in a
      randomized trial.

PMID- 24872363
TI  - The utility of Bayesian predictive probabilities for interim monitoring of
      clinical trials.
AB  - BACKGROUND: Bayesian predictive probabilities can be used for interim monitoring
      of clinical trials to estimate the probability of observing a statistically
      significant treatment effect if the trial were to continue to its predefined
      maximum sample size. PURPOSE: We explore settings in which Bayesian predictive
      probabilities are advantageous for interim monitoring compared to Bayesian
      posterior probabilities, p-values, conditional power, or group sequential
      methods. RESULTS: For interim analyses that address prediction hypotheses, such
      as futility monitoring and efficacy monitoring with lagged outcomes, only
      predictive probabilities properly account for the amount of data remaining to be
      observed in a clinical trial and have the flexibility to incorporate additional
      information via auxiliary variables. LIMITATIONS: Computational burdens limit the
      feasibility of predictive probabilities in many clinical trial settings. The
      specification of prior distributions brings additional challenges for regulatory
      approval. CONCLUSIONS: The use of Bayesian predictive probabilities enables the
      choice of logical interim stopping rules that closely align with the clinical
      decision-making process.

PMID- 24872364
TI  - Proximal Tibial Anterior Closing Wedge Osteotomy in Repeat Revision of Anterior
      Cruciate Ligament Reconstruction.
AB  - BACKGROUND: Physicians should consider an increased posterior tibial slope (PTS)
      as a risk factor for graft failure when proposing anterior cruciate ligament
      (ACL) re-revision. PURPOSE: To describe the surgical technique of combined ACL
      revision and proximal tibial anterior closing wedge osteotomy and to evaluate its
      clinical outcome in cases of recurrent graft failure with associated increased
      tibial slope. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Between
      2008 and 2010, 5 combined ACL re-revisions with proximal tibial anterior closing
      wedge osteotomy were retrospectively evaluated after a mean 31.6 months' follow
      up (range, 23-45 months). All patients reported subjective knee instability
      preoperatively and demonstrated increased laxity on physical examination.
      Intrinsic risk factors for graft failure (excessive tibial slope) were identified
      in all cases. Preoperative and postoperative functional assessments included the
      International Knee Documentation Committee (IKDC) score along with the Lysholm
      score and Tegner activity scale. RESULTS: The mean Lysholm score was 46.2
      preoperatively (range, 26-69) and 87.8 (range, 60-100) postoperatively. The mean
      IKDC subjective score was 39.5 (range, 21.8-64.4) before surgery and 79.1 (range,
      48.3-98.9) at the last follow-up. The mean Tegner activity score was 7.4 (range,
      5-9) before the latest ACL injury and 7.2 (range, 5-9) at the last follow-up. The
      mean PTS was 13.6 degrees  (range, 13 degrees -14 degrees ) preoperatively and
      9.2 degrees  (range, 8 degrees -10 degrees ) postoperatively (P = .0005). The
      mean differential anterior laxity was 10.4 mm (range, 8-14 mm), and this
      significantly decreased to 2.8 mm (range, 2-4 mm) at the last follow-up. Using
      the Kellgren-Lawrence classification to evaluate the presence of arthritis, 1
      patient was grade 1, 3 patients were grade 2, and 1 patient was grade 3.
      CONCLUSION: Combined ACL re-revision with proximal tibial anterior closing wedge
      osteotomy restores knee stability and function with satisfactory clinical
      outcomes in patients who experience recurrent ACL ruptures with an associated
      increased PTS.

PMID- 24872366
TI  - A baby boy with hypothyroidism and hemangioendothelioma.

PMID- 24872367
TI  - Commentary.

PMID- 24872365
TI  - Up-regulation of Glutamate in Painful Human Supraspinatus Tendon Tears.
AB  - BACKGROUND: Pain related to rotator cuff tendinopathy is a common problem, but
      little is known regarding the origin and cause of pain from the tendon substance.
      No study to date has looked at the association between tissue changes and patient
      outcomes. PURPOSE: To describe the peripheral neuronal phenotype in painful
      rotator cuff tears and to determine correlations between tissue changes and
      clinical outcome measures. STUDY DESIGN: Controlled laboratory study. METHODS:
      Tissue samples of the supraspinatus were taken from patients undergoing surgery
      to repair a rotator cuff tendon tear. Patients were classified as having
      small/medium or large/massive tears. Control tissue was obtained from patients
      undergoing surgery for posttraumatic shoulder instability. Immunohistochemical
      techniques were performed using antibodies to known nociceptive and neuronal
      markers as well as general tissue structural markers. RESULTS: There was no
      correlation between tissue changes and patient-reported outcomes. A significant
      increase in the expression of glutamate was seen in tendon tears. There were
      differences in the expression of metabotropic and ionotropic glutamate receptors.
      Expression changes were also observed for markers of the sensory and autonomic
      systems; however, no differences were found in neurotrophins. CONCLUSION:
      Glutamate and the glutaminergic system play a key role in painful human tendon
      tears; however, the exact role is still uncertain, as glutamate is highly
      involved in both pain and metabolic pathways. CLINICAL RELEVANCE: This study has
      identified a number of markers that could be potential therapeutic targets.

PMID- 24872368
TI  - Commentary.

PMID- 24872369
TI  - Low plasma glucose with normal finger-stick glucose.

PMID- 24872370
TI  - Increased aminotransferases in a 12-year-old girl.

PMID- 24872371
TI  - Losing the MRSA label.

PMID- 24872373
TI  - The aesthetics of texts: medieval illuminated manuscripts.

PMID- 24872374
TI  - Condylomata acuminata within perianal fistulae tracts: report of two cases.
AB  - The commonest sights of appearance of condylomata acuminata are in the genital
      and anal regions. Herein we present two cases of condylomata within perianal
      fistulae tracts, resulting in recurrence in one case and a malignant-like tumour
      in the second. To our knowledge, these are the first cases reported in the
      literature. 

PMID- 24872375
TI  - Clinically significant extra-cardiac findings in asymptomatic HIV-positive men
      undergoing cardiac magnetic resonance imaging.
AB  - Increased research-based imaging has led to an increase in clinically significant
      extra-cardiac findings. HIV patients are at increased risk of having
      polypathology at a younger age; therefore, it may be hypothesised that they would
      have more incidental findings on imaging. We reviewed the magnetic resonance
      imaging results of 169 HIV-positive and 40 HIV-negative, clinically well
      volunteers undergoing cardiac magnetic resonance imaging scanning to assess the
      prevalence of subclinical cardiac pathology. This sub-study assessed the
      prevalence of clinically significant extra-cardiac findings. Associated risk
      factors were assessed and clinical follow-up and outcome were ascertained. Of the
      HIV-positive study group, 12/169 (7.1%) vs. 1/40 (2.5%) control patients had a
      clinically significant extra-cardiac finding which warranted further radiological
      or clinical intervention (p = 0.28). A total of three out of 169 (1.1%) were
      highly clinically significant findings. On logistic regression analysis, age was
      the only significant contributing factor (p = 0.049); no HIV-associated factors
      were found to be significant. The prevalence of clinically significant extra
      cardiac findings of 7.1% in this HIV-positive cohort is comparable to the
      prevalence found in previous studies carried out on an older, sicker general
      population. This highlights the need for planning for unexpected outcomes and
      also the high rate of clinically significant findings in a seemingly well HIV
      positive population. 

PMID- 24872376
TI  - Identity development in deaf adolescents.
AB  - We studied identity development during 5 years in seven deaf adolescents who
      attended a school for deaf children in the highest level of regular secondary
      education (age between 14 and 18 years), administering identity interviews every
      year. Identity development is conceptualized as the processes of exploration and
      commitment formation (Bosma, 1985). We started from the assumption that because
      deaf adolescents meet more challenges and also-in our sample-were stimulated in
      their identity development by school programs, they meet identity conflicts at a
      relatively early age. The findings were highly consistent with our hypotheses
      that-compared to a general sample-identity development proceeds faster than in a
      hearing group and that commitment formation in the domain "Being Deaf" starts
      earlier than in other domains. We did not find evidence for the hypothesis that
      commitment formation in this domain in the last year was more mature than in
      other domains due to a ceiling effect. 

PMID- 24872378
TI  - Investigation of metabolism and disposition of GSK1322322, a peptidase
      deformylase inhibitor, in healthy humans using the entero-test for biliary
      sampling.
AB  - GSK1322322 (N-((R)-2-(cyclopentylmethyl)-3-(2-(5-fluoro-6-((S)
      hexahydropyrazino[2,1-c][1,4]oxazin-8(1H)-yl)-2-methylpyrimidin-4-yl)hydrazinyl)
      3-oxopropyl)-N-hydroxy-formamide) is an antibiotic in development by
      GlaxoSmithKline. In this study, we investigated the metabolism and disposition of
      [(14)C]GSK1322322 in healthy humans and demonstrated the utility of the Entero
      Test in a human radiolabel study. We successfully collected bile from five men
      using this easy-to-use device after single i.v. (1000 mg) or oral administration
      (1200 mg in a solution) of [(14)C]GSK1322322. GSK1322322 had low plasma clearance
      (23.6 liters/hour) with a terminal elimination half-life of ~4 hours after i.v.
      administration. After oral administration, GSK1322322 was readily and almost
      completely absorbed (time of maximal concentration of 0.5 hour; bioavailability
      97%). GSK1322322 predominated in the systemic circulation (>64% of total plasma
      radioactivity). An O-glucuronide of GSK1322322 (M9) circulated at levels between
      10% and 15% of plasma radioactivity and was pharmacologically inactive. Humans
      eliminated the radioactive dose in urine and feces at equal proportions after
      both i.v. and oral doses (~45%-48% each). Urine contained mostly unchanged
      GSK1322322, accounting for 30% of the dose. Bile contained mostly M9, indicating
      that glucuronidation was likely a major pathway in humans (up to 30% of total
      dose). In contrast, M9 was found in low amounts in feces, indicating its
      instability in the gastrointestinal tract. Therefore, without the Entero-Test
      bile data, the contribution of glucuronidation would have been notably
      underestimated. An unusual N-dehydroxylated metabolite (a secondary amide) of
      GSK1322322 was observed primarily in the feces and was most likely formed by gut
      microbes. 

PMID- 24872377
TI  - Impact of a nurse-led programme on comorbidity management and impact of a patient
      self-assessment of disease activity on the management of rheumatoid arthritis:
      results of a prospective, multicentre, randomised, controlled trial (COMEDRA).
AB  - OBJECTIVES: Rheumatoid arthritis (RA) patients are at an increased risk of
      developing comorbid conditions. A close monitoring of the disease targeting a
      status of low disease activity is associated with a better outcome. The aim of
      this trial was to evaluate the impact of a nurse-led programme on comorbidities
      and the impact of patient self-assessment of disease activity on the management
      of RA. METHODS: We enrolled 970 patients (mean age 58 years, 79% women) in a
      prospective, randomised, controlled, open-label, 6-month trial. In the
      comorbidity group (n=482), the nurse checked comorbidities and sent the programme
      results to the attending physicians. In the self-assessment group (n=488), the
      nurse taught the patient how to calculate his/her Disease Activity Score which
      had to be reported on a booklet to be shared with the treating rheumatologist.
      The number of measures taken for comorbidities and the percentage of patients
      recording a change (initiation, switch or increased dose) in disease-modifying
      antirheumatic drugs (DMARDs) in the 6 months follow-up period of the study
      defined the outcomes of the trial. RESULTS: The number of measures taken per
      patient was statistically higher in the comorbidity group: 4.54+/-2.08 versus
      2.65+/-1.57 (p<0.001); incidence rate ratio: 1.78 (1.61-1.96) and DMARD therapy
      was changed more frequently in the self-assessment group: 17.2% versus 10.9%
      (OR=1.70 (1.17; 2.49), p=0.006). CONCLUSIONS: This study demonstrates the short
      term benefit of a nurse-led programme on RA comorbidity management and the impact
      of patient self-assessment of disease activity on RA treatment intensification.
      TRIAL REGISTRATION NUMBER: NCT #01315652.

PMID- 24872379
TI  - Ribosomal Protein RPL27a Promotes Female Gametophyte Development in a Dose
      Dependent Manner.
AB  - Ribosomal protein mutations in Arabidopsis (Arabidopsis thaliana) result in a
      range of specific developmental phenotypes. Why ribosomal protein mutants have
      specific phenotypes is not fully known, but such defects potentially result from
      ribosome insufficiency, ribosome heterogeneity, or extraribosomal functions of
      ribosomal proteins. Here, we report that ovule development is sensitive to the
      level of Ribosomal Protein L27a (RPL27a) and is disrupted by mutations in the two
      paralogs RPL27aC and RPL27aB. Mutations in RPL27aC result in high levels of
      female sterility, whereas mutations in RPL27aB have a significant but lesser
      effect on fertility. Progressive reduction in RPL27a function results in
      increasing sterility, indicating a dose-dependent relationship between RPL27a and
      female fertility. RPL27a levels in both the sporophyte and gametophyte affect
      female gametogenesis, with different developmental outcomes determined by the
      dose of RPL27a. These results demonstrate that RPL27aC and RPL27aB act
      redundantly and reveal a function for RPL27a in coordinating complex interactions
      between sporophyte and gametophyte during ovule development.

PMID- 24872380
TI  - Enhanced Disease Susceptibility1 Mediates Pathogen Resistance and Virulence
      Function of a Bacterial Effector in Soybean.
AB  - Enhanced disease susceptibility1 (EDS1) and phytoalexin deficient4 (PAD4) are
      well-known regulators of both basal and resistance (R) protein-mediated plant
      defense. We identified two EDS1-like (GmEDS1a/GmEDS1b) proteins and one PAD4-like
      (GmPAD4) protein that are required for resistance signaling in soybean (Glycine
      max). Consistent with their significant structural conservation to Arabidopsis
      (Arabidopsis thaliana) counterparts, constitutive expression of GmEDS1 or GmPAD4
      complemented the pathogen resistance defects of Arabidopsis eds1 and pad4
      mutants, respectively. Interestingly, however, the GmEDS1 and GmPAD4 did not
      complement pathogen-inducible salicylic acid accumulation in the eds1/pad4
      mutants. Furthermore, the GmEDS1a/GmEDS1b proteins were unable to complement the
      turnip crinkle virus coat protein-mediated activation of the Arabidopsis R
      protein Hypersensitive reaction to Turnip crinkle virus (HRT), even though both
      interacted with HRT. Silencing GmEDS1a/GmEDS1b or GmPAD4 reduced basal and
      pathogen-inducible salicylic acid accumulation and enhanced soybean
      susceptibility to virulent pathogens. The GmEDS1a/GmEDS1b and GmPAD4 genes were
      also required for Resistance to Pseudomonas syringae pv glycinea2 (Rpg2)-mediated
      resistance to Pseudomonas syringae. Notably, the GmEDS1a/GmEDS1b proteins
      interacted with the cognate bacterial effector AvrA1 and were required for its
      virulence function in rpg2 plants. Together, these results show that despite
      significant structural similarities, conserved defense signaling components from
      diverse plants can differ in their functionalities. In addition, we demonstrate a
      role for GmEDS1 in regulating the virulence function of a bacterial effector.

PMID- 24872381
TI  - Lipoate-Protein Ligase and Octanoyltransferase Are Essential for Protein
      Lipoylation in Mitochondria of Arabidopsis.
AB  - Prosthetic lipoyl groups are required for the function of several essential
      multienzyme complexes, such as pyruvate dehydrogenase (PDH), alpha-ketoglutarate
      dehydrogenase (KGDH), and the glycine cleavage system (glycine decarboxylase
      [GDC]). How these proteins are lipoylated has been extensively studied in
      prokaryotes and yeast (Saccharomyces cerevisiae), but little is known for plants.
      We earlier reported that mitochondrial fatty acid synthesis by ketoacyl-acyl
      carrier protein synthase is not vital for protein lipoylation in Arabidopsis
      (Arabidopsis thaliana) and does not play a significant role in roots. Here, we
      identify Arabidopsis lipoate-protein ligase (AtLPLA) as an essential
      mitochondrial enzyme that uses octanoyl-nucleoside monophosphate and possibly
      other donor substrates for the octanoylation of mitochondrial PDH-E2 and GDC H
      protein; it shows no reactivity with bacterial and possibly plant KGDH-E2. The
      octanoate-activating enzyme is unknown, but we assume that it uses octanoyl
      moieties provided by mitochondrial beta-oxidation. AtLPLA is essential for the
      octanoylation of PDH-E2, whereas GDC H-protein can optionally also be
      octanoylated by octanoyltransferase (LIP2) using octanoyl chains provided by
      mitochondrial ketoacyl-acyl carrier protein synthase to meet the high lipoate
      requirement of leaf mesophyll mitochondria. Similar to protein lipoylation in
      yeast, LIP2 likely also transfers octanoyl groups attached to the H-protein to
      KGDH-E2 but not to PDH-E2, which is exclusively octanoylated by LPLA. We suggest
      that LPLA and LIP2 together provide a basal protein lipoylation network to plants
      that is similar to that in other eukaryotes.

PMID- 24872383
TI  - The paediatric voice clinic.
AB  - BACKGROUND: Prevalence of paediatric voice disorders has been reported as 6-9% in
      children of school age. The appropriate diagnosis and management of paediatric
      voice disorders is essential for progress in education and psychosocial
      development. This paper presents a review of a UK tertiary paediatric voice
      clinic experience of referral patterns, diagnosis, management and socioeconomic
      variations. METHODS: An audit of 195 consecutive appointments (154 were new
      patients) between October 2009 and September 2013 at a monthly paediatric voice
      clinic based at the Royal Hospital for Sick Children in Glasgow. RESULTS: Of the
      154 new patients, 86 were male and 68 were female. The age at first clinic
      appointment shows a trimodal peak at ages 5, 8 and 11 years. General
      practitioners were the main referral source (46%). Vocal cord nodules accounted
      for 52% of diagnoses with a male predominance. Clinic attendance was most common
      from Scottish Index of Multiple Deprivation groups 1 (most deprived) and 5 (least
      deprived). Analysis of the muscle tension dysphonia group indicates that they are
      more likely to come from social groups 4 or 5 (69%) and an older age group (mean
      age 10.4 years). DISCUSSION: A dedicated paediatric voice clinic is the optimal
      method for assessment, diagnosis and management of these patients. Diagnosis is
      possible on the majority of the patients in clinic, with the predominant
      pathology being vocal cord nodules that receive speech and language therapy.
      Socioeconomic group appears to have an influence on paediatric voice particularly
      vocal cord nodules and muscle tension dysphonia.

PMID- 24872384
TI  - The science of paediatrics, child health research, and the Royal College of
      Paediatrics and Child Health.

PMID- 24872385
TI  - The impact of diabetes self-management education on glucose management and
      empowerment in ethnic Armenians with type 2 diabetes.
AB  - PURPOSE: The purpose of this study was to investigate the impact of diabetes self
      management education on glycemic control and perceptions of empowerment in
      Armenian American immigrants diagnosed with type 2 diabetes. METHODS: A quasi
      experimental pre and post design was used to investigate the impact of using
      education on self-management as measured by A1C levels and empowerment scores.
      Nine hours of diabetes self-management education classes were offered in the
      Armenian language to 75 clients at 2 adult health day care centers over 6 weeks.
      The participants were mostly first-generation Armenian immigrants aged 65 years
      and older. A1C results, the 8-item Diabetes Empowerment Scale (DES), and the 15
      item Armenian Ethnic Orientation Questionnaire-Revised (AEOQ-R) were used to
      determine the impact of education on self-care management. RESULTS: After
      institutional review board approval was obtained, 75 participants completed the
      study. A paired t test indicated that the postintervention mean A1C level was
      significantly lower than the preintervention mean A1C level. The postintervention
      mean DES score was significantly greater than the preintervention mean DES score.
      No mediating effects of age, gender, acculturation, and number of years with the
      disease were identified for either A1C or DES score. CONCLUSIONS: The findings
      demonstrate the efficacy of the diabetes self-management education classes in
      improving diabetes self-care management skills.

PMID- 24872382
TI  - Epigenetics: Beyond Chromatin Modifications and Complex Genetic Regulation.
AB  - Chromatin modifications and epigenetics may play important roles in many plant
      processes, including developmental regulation, responses to environmental
      stimuli, and local adaptation. Chromatin modifications describe biochemical
      changes to chromatin state, such as alterations in the specific type or placement
      of histones, modifications of DNA or histones, or changes in the specific
      proteins or RNAs that associate with a genomic region. The term epigenetic is
      often used to describe a variety of unexpected patterns of gene regulation or
      inheritance. Here, we specifically define epigenetics to include the key aspects
      of heritability (stable transmission of gene expression states through mitotic or
      meiotic cell divisions) and independence from DNA sequence changes. We argue
      against generically equating chromatin and epigenetics; although many examples of
      epigenetics involve chromatin changes, those chromatin changes are not always
      heritable or may be influenced by genetic changes. Careful use of the terms
      chromatin modifications and epigenetics can help separate the biochemical
      mechanisms of regulation from the inheritance patterns of altered chromatin
      states. Here, we also highlight examples in which chromatin modifications and
      epigenetics affect important plant processes.

PMID- 24872386
TI  - A qualitative study of acculturation and diabetes risk among urban immigrant
      Latinas: implications for diabetes prevention efforts.
AB  - PURPOSE: The purpose of this qualitative study was to understand how
      acculturation influences diabetes risk among urban immigrant Latinas (Hispanic
      women). METHODS: Five focus groups were conducted with 26 urban immigrant Latinas
      who were at high clinical risk for developing diabetes. The focus group sessions
      were audiotaped and transcribed verbatim. The authors independently analyzed
      transcripts using an inductive method of open coding and established themes by
      consensus. RESULTS: All participants were foreign born and had low levels of
      acculturation. During the acculturation process, they noted changes in their
      lifestyle behaviors and the family context in which those behaviors are shaped.
      They reported that since living in the United States, their improved economic
      circumstances led to increased consumption of less healthy foods and beverages
      and a more sedentary lifestyle. They also described changing family roles and
      responsibilities, including working outside the home, which constrained healthy
      food choices. However, they perceived that their position of influence within the
      family offered opportunities to help family members prevent diabetes.
      CONCLUSIONS: Lifestyle interventions to prevent diabetes in Latinas should
      address their acculturation experiences, which affect family functioning and
      health behaviors related to diabetes risk. For example, given the perceived link
      between Latinas' improved economic circumstances and their diabetes risk,
      prevention programs should incorporate strategies to help Latinas avoid adopting
      less healthy lifestyle behaviors that become affordable during the acculturation
      process.

PMID- 24872388
TI  - Inhibition of miR-17 and miR-20a by oridonin triggers apoptosis and reverses
      chemoresistance by derepressing BIM-S.
AB  - Cancer cell chemoresistance arises in part through the acquisition of apoptotic
      resistance. Leukemia cells resistant to chemotherapy-induced apoptosis have been
      found to be sensitive to oridonin, a natural agent with potent anticancer
      activity. To investigate its mechanisms of action in reversing chemoresistance,
      we compared the response of human leukemia cells with oridonin and the
      antileukemia drugs Ara-C and VP-16. Compared with HL60 cells, K562 and K562/ADR
      cells displayed resistance to apoptosis stimulated by Ara-C and VP-16 but
      sensitivity to oridonin. Mechanistic investigations revealed that oridonin
      upregulated BIM-S by diminishing the expression of miR-17 and miR-20a, leading to
      mitochondria-dependent apoptosis. In contrast, neither Ara-C nor VP-16 could
      reduce miR-17 and miR-20a expression or could trigger BIM-S-mediated apoptosis.
      Notably, silencing miR-17 or miR-20a expression by treatment with microRNA
      (miRNA; miR) inhibitors or oridonin restored sensitivity of K562 cells to VP-16.
      Synergistic effects of oridonin and VP-16 were documented in cultured cells as
      well as mouse tumor xenograft assays. Inhibiting miR-17 or miR-20a also augmented
      the proapoptotic activity of oridonin. Taken together, our results identify a
      miRNA-dependent mechanism underlying the anticancer effect of oridonin and
      provide a rationale for its combination with chemotherapy drugs in addressing
      chemoresistant leukemia cells.

PMID- 24872387
TI  - Selenium suppresses leukemia through the action of endogenous eicosanoids.
AB  - Eradicating cancer stem-like cells (CSC) may be essential to fully eradicate
      cancer. Metabolic changes in CSC could hold a key to their targeting. Here, we
      report that the dietary micronutrient selenium can trigger apoptosis of CSC
      derived from chronic or acute myelogenous leukemias when administered at
      supraphysiologic but nontoxic doses. In leukemia CSC, selenium treatment
      activated ATM-p53-dependent apoptosis accompanied by increased intracellular
      levels of reactive oxygen species. Importantly, the same treatment did not
      trigger apoptosis in hematopoietic stem cells. Serial transplantation studies
      with BCR-ABL-expressing CSC revealed that the selenium status in mice was a key
      determinant of CSC survival. Selenium action relied upon the endogenous
      production of the cyclooxygenase-derived prostaglandins Delta(12)-PGJ2 and 15d
      PGJ2. Accordingly, nonsteroidal anti-inflammatory drugs and NADPH oxidase
      inhibitors abrogated the ability of selenium to trigger apoptosis in leukemia
      CSC. Our results reveal how selenium-dependent modulation of arachidonic acid
      metabolism can be directed to trigger apoptosis of primary human and murine CSC
      in leukemia.

PMID- 24872393
TI  - Dengue human infection model: introduction.

PMID- 24872389
TI  - hMOB3 modulates MST1 apoptotic signaling and supports tumor growth in
      glioblastoma multiforme.
AB  - New therapeutic targets are needed that circumvent inherent therapeutic
      resistance of glioblastoma multiforme (GBM). Here, we report such a candidate
      target in the uncharacterized adaptor protein hMOB3, which we show is upregulated
      in GBM. In a search for its biochemical function, we found that hMOB3
      specifically interacts with MST1 kinase in response to apoptotic stimuli and cell
      cell contact. Moreover, hMOB3 negatively regulated apoptotic signaling by MST1 in
      GBM cells by inhibiting the MST1 cleavage-based activation process. Physical
      interaction between hMOB3 and MST1 was essential for this process. In vivo
      investigations established that hMOB3 sustains GBM cell growth at high cell
      density and promotes tumorigenesis. Our results suggest hMOB3 as a candidate
      therapeutic target for the treatment of malignant gliomas.

PMID- 24872394
TI  - Controlled human malaria infection.
AB  - BACKGROUND: Since 1986, investigators at Walter Reed Army Institute of Research
      (WRAIR) have been using controlled human malaria challenge (CHMI) in malaria
      naive adults in order to define the protective efficacy of a malaria vaccine and
      thus guide programmatic decisions on vaccine candidates. Adapting this model to
      the dengue field could provide similar evidential support for a vaccine or
      therapeutic product. METHODS: After completing a vaccine regimen, volunteers are
      bitten by 5 malaria-infected female Anopheles mosquitoes in a controlled
      environment. Volunteers are then monitored daily for peripheral parasitemia in a
      hotel setting with 24-hour access to a nurse and physician. If a single verified
      parasite is detected, effective antimalarials are promptly administered. RESULTS:
      The vast majority of the over 1000 volunteers having participated in CHMI
      clinical studies have done so at US military research centers. Numerous pre
      erythrocytic and erythrocytic vaccine candidates have been evaluated safely and
      without any related serious adverse events using this model, including the soon
      to-be licensed RTS,S malaria vaccine. CONCLUSION: The lessons learned from over
      25 years of experience in consistent, careful preparation and execution of the
      CHMI model at WRAIR can provide a foundation from which the dengue field can
      begin to develop a rigorous and safe "CHDI" model.

PMID- 24872395
TI  - Production and testing of dengue virus strains suitable for human infection
      studies.
AB  - Vaccine efficacy can be assessed in human subjects who have received dengue virus
      (DENV) candidate vaccines. Recent, published studies have been conducted with
      DENV strains that resulted in a spectrum of clinical disease. DENV-1 and DENV-3
      strains were identified that could be used to test for protection against these
      serotypes. DENV strains that are intended for similar human clinical studies
      require production and preclinical testing that are the same as vaccines entering
      Phase 1 human clinical testing. Information on passage history, use of raw
      materials, testing for adventitious agents, complete characterization (including
      genetic sequence), and product stability are essential for DENV strain banks
      intended for human infection studies.

PMID- 24872396
TI  - The human dengue challenge experience at the Walter Reed Army Institute of
      Research.
AB  - Recent discordance between measured levels of serotypes of dengue virus
      neutralizing antibody and clinical outcomes suggests a need to reevaluate the
      process of prescreening dengue vaccine candidates to better predict their
      clinical benefit before initiation of large-scale human vaccine trials. In the
      absence of a reliable animal model for dengue, a human dengue virus challenge
      model (ie, a controlled live dengue virus infectious challenge study) may prove
      useful and timely to elucidate mechanisms that underlie protection (as well as
      virulence), thus facilitating down-selection of vaccine candidates before
      beginning advanced field trials. Dengue challenge studies were safely used in
      prior decades to study the vector biology, clinical spectrum of illness, and
      reactogenicity of candidate live dengue virus vaccines of uncertain attenuation.
      Redeveloping the human dengue challenge model following current regulatory
      guidance, good manufacturing practice, and good clinical practice could
      streamline and accelerate vaccine development by offering a time- and resource
      efficient method to evaluate the safety and potential efficacy of dengue vaccine
      and therapeutic candidates. In this article, the development of such a challenge
      model and its subsequent application is summarized from 2 recent reports.

PMID- 24872397
TI  - Dengue human infection model performance parameters.
AB  - Dengue is a global health problem and of concern to travelers and deploying
      military personnel with development and licensure of an effective tetravalent
      dengue vaccine a public health priority. The dengue viruses (DENVs) are mosquito
      borne flaviviruses transmitted by infected Aedes mosquitoes. Illness manifests
      across a clinical spectrum with severe disease characterized by intravascular
      volume depletion and hemorrhage. DENV illness results from a complex interaction
      of viral properties and host immune responses. Dengue vaccine development efforts
      are challenged by immunologic complexity, lack of an adequate animal model of
      disease, absence of an immune correlate of protection, and only partially
      informative immunogenicity assays. A dengue human infection model (DHIM) will be
      an essential tool in developing potential dengue vaccines or antivirals. The
      potential performance parameters needed for a DHIM to support vaccine or
      antiviral candidates are discussed.

PMID- 24872398
TI  - DHIM supporting immunologic investigations and the identification of immune
      correlates of protection.
AB  - Evidence suggesting that immune responses to dengue virus (DENV) have the
      potential for both beneficial and detrimental effects on the outcome of infection
      is a concern for dengue vaccine development. There is thus a great need to define
      measures of DENV-specific immune responses that reliably indicate when immunity
      is protective. The existence of 4 main DENV serotypes and the difficulty in
      defining which individuals have been exposed and to which viruses present
      challenges to defining immune correlates of protective immunity against DENV in
      field efficacy studies; experimental infection studies in humans offer a pathway
      to address these challenges.

PMID- 24872399
TI  - Dengue human infection models supporting drug development.
AB  - Dengue is a arboviral infection that represents a major global health burden.
      There is an unmet need for effective dengue therapeutics to reduce symptoms,
      duration of illness and incidence of severe complications. Here, we consider the
      merits of a dengue human infection model (DHIM) for drug development. A DHIM
      could allow experimentally controlled studies of candidate therapeutics in
      preselected susceptible volunteers, potentially using smaller sample sizes than
      trials that recruited patients with dengue in an endemic country. In addition,
      the DHIM would assist the conduct of intensive pharmacokinetic and basic research
      investigations and aid in determining optimal drug dosage. Furthermore, a DHIM
      could help establish proof of concept that chemoprophylaxis against dengue is
      feasible. The key challenge in developing the DHIM for drug development is to
      ensure the model reliably replicates the typical clinical and laboratory features
      of naturally acquired, symptomatic dengue.

PMID- 24872401
TI  - Causes, consequences and solutions of phylogenetic incongruence.
AB  - Phylogenetic analysis is used to recover the evolutionary history of species,
      genes or proteins. Understanding phylogenetic relationships between organisms is
      a prerequisite of almost any evolutionary study, as contemporary species all
      share a common history through their ancestry. Moreover, it is important because
      of its wide applications that include understanding genome organization,
      epidemiological investigations, predicting protein functions, and deciding the
      genes to be analyzed in comparative studies. Despite immense progress in recent
      years, phylogenetic reconstruction involves many challenges that create
      uncertainty with respect to the true evolutionary relationships of the species or
      genes analyzed. One of the most notable difficulties is the widespread occurrence
      of incongruence among methods and also among individual genes or different
      genomic regions. Presence of widespread incongruence inhibits successful
      revealing of evolutionary relationships and applications of phylogenetic
      analysis. In this article, I concisely review the effect of various factors that
      cause incongruence in molecular phylogenies, the advances in the field that
      resolved some factors, and explore unresolved factors that cause incongruence
      along with possible ways for tackling them. 

PMID- 24872402
TI  - Effect of tirasemtiv, a selective activator of the fast skeletal muscle troponin
      complex, in patients with peripheral artery disease.
AB  - Tirasemtiv (CK-2017357), a novel small-molecule activator of the fast skeletal
      muscle troponin complex, slows the rate of calcium release from troponin, thus
      sensitizing fast skeletal muscle fibers to calcium. In preclinical studies,
      tirasemtiv increased muscle force and delayed the onset and reduced the extent of
      muscle fatigue during hypoxia in vitro and muscle ischemia in situ. This study
      evaluated the effect of single doses of tirasemtiv on measures of skeletal muscle
      function and fatigability in patients with stable calf claudication due to
      peripheral artery disease (PAD). Sixty-one patients with an ankle-brachial index
      <=0.90 in the leg with claudication received single double-blind doses of
      tirasemtiv 375 mg and 750 mg and matching placebo in random order about 1 week
      apart. After 33 patients were treated, the 750 mg dose was decreased to 500 mg
      due to adverse events and these dose groups were combined for analysis. On each
      study day, bilateral heel-raise testing was performed before and at 3 and 6 hours
      after dosing; a 6-minute walk test was performed at 4 hours after dosing.
      Claudicating calf muscle performance was increased at the highest dose and plasma
      concentration of tirasemtiv; however, the 6-minute walk distance decreased with
      both the dose and plasma concentration of tirasemtiv, possibly due to dose
      related adverse events, particularly dizziness, that could impede walking
      ability. In conclusion, the mechanism of fast skeletal muscle troponin activation
      improved muscle function but not 6-minute walking distance in patients with
      claudication due to PAD. CLINICALTRIALSGOV IDENTIFIER NCT01131013:

PMID- 24872400
TI  - The role of the mosquito in a dengue human infection model.
AB  - Recent efforts to combat the growing global threat of dengue disease, including
      deployment of phase IIb vaccine trials, has continued to be hindered by
      uncertainty surrounding equitable immune responses of serotypes, relative viral
      fitness of vaccine vs naturally occurring strains, and the importance of altered
      immune environments due to natural delivery routes. Human infection models can
      significantly improve our understanding of the importance of certain phenotypic
      characteristics of viral strains, and inform strain selection and trial design.
      With human models, we can further assess the importance of the natural delivery
      route of DENV and/or the accompanying mosquito salivary milieu. Accordingly, we
      discuss the use of mosquitoes in such a human infection model with DENV, identify
      important considerations, and make preliminary recommendations for deployment of
      such a mosquito improved DENV human infection model (miDHIM).

PMID- 24872403
TI  - Clinical and socioeconomic factors associated with unrecognized peripheral artery
      disease.
AB  - Peripheral artery disease (PAD) is a highly prevalent condition that frequently
      goes undetected and untreated. Socioeconomic factors associated with unrecognized
      PAD are not known. The ankle-brachial index (ABI) was calculated in 1656 study
      participants undergoing non-emergent coronary angiography with PAD defined as an
      ABI <0.9. Subjects were followed for mortality and cardiovascular outcomes.
      Compared to those without PAD, those with unrecognized PAD at enrollment were
      older, had higher rates of cardiovascular comorbidities, and had higher major
      adverse cardiovascular events (MACE) (p<0.03 for all). Among those enrolling
      without a reported history of PAD, there was a higher prevalence of PAD with
      decreasing income (p=0.004), education level (p<0.001), social isolation
      (p=0.027) and depression (p=0.034); 50% of these individuals reported symptoms
      suggestive of claudication. In conclusion, the prevalence of unrecognized PAD is
      high amongst a cohort of high-risk individuals referred for coronary angiography.
      A profile of lower socioeconomic status is associated with unrecognized PAD.
      These subjects will report symptoms suggestive of claudication and impaired
      walking ability when directly queried.

PMID- 24872404
TI  - Pre-operative risk stratification for cancer-specific survival in patients with
      renal cell carcinoma with venous involvement who underwent nephrectomy.
AB  - OBJECTIVE: The aim of this study is to identify the pre-operative prognostic
      factors and create a risk stratification model for patients with renal cell
      carcinoma with extension into the renal vein or inferior vena cava. METHODS: The
      study cohort included 61 patients with renal cell carcinoma extending into the
      renal vein or inferior vena cava that underwent operations between 1993 and 2012.
      Cancer-specific survival rates were estimated, and univariate and multivariate
      analyses were carried out to determine the prognostic factors. A simple risk
      stratification model was developed for these patients. RESULTS: The median follow
      up period of the current patient cohort was 33.7 months. Their 1, 3 and 5-year
      cancer-specific survival were 89, 70 and 65%, respectively. On multivariate
      analysis, the level of tumor thrombus extension (extension into the
      supradiaphragm), presence of distant metastasis and elevation of lactate
      dehydrogenase and C-reactive protein were independent negative prognostic factors
      for cancer-specific survival. Cancer-specific survival rates were clearly
      discriminated by the stratification according to the scoring model (P < 0.001).
      The concordance index of the new model was 0.80. CONCLUSIONS: We demonstrated a
      simple risk stratification model with four pre-operative independent prognostic
      factors for patients with renal cell carcinoma with venous involvement. This may
      be a useful decision-making model in the management of such patients.

PMID- 24872405
TI  - Successful crizotinib rechallenge after crizotinib-induced interstitial lung
      disease.
AB  - We report the case of a 70-year-old Japanese male diagnosed with advanced lung
      adenocarcinoma harboring the echinoderm microtubule-associated protein-like 4
      anaplastic lymphoma kinase fusion gene. As soon as crizotinib was administered,
      tumor shrank immediately. On Day 25, he developed interstitial lung disease.
      Bronchoalveolar lavage fluid analysis demonstrated elevated lymphocytes
      fractionation. A drug lymphocyte stimulating test for crizotinib with the
      bronchoalveolar lavage lymphocytes was negative. Crizotinib administration was
      discontinued, but a life-threatening flare of tumor growth occurred. Since there
      was no alternative treatment for the lung cancer, we restarted crizotinib in
      combination with prednisolone. The patient experienced neither disease
      progression nor recurrence of interstitial lung disease at 6 months. In cases in
      which no alternate treatment is known, crizotinib retreatment combined with
      steroid therapy after crizotinib-induced interstitial lung disease could be
      considered after a careful consideration of the potential risks and benefits. 

PMID- 24872406
TI  - Challenges in accurate quantitation of lysophosphatidic acids in human biofluids.
AB  - Lysophosphatidic acids (LPAs) are biologically active signaling molecules
      involved in the regulation of many cellular processes and have been implicated as
      potential mediators of fibroblast recruitment to the pulmonary airspace, pointing
      to possible involvement of LPA in the pathology of pulmonary fibrosis. LPAs have
      been measured in various biological matrices and many challenges involved with
      their analyses have been documented. However, little published information is
      available describing LPA levels in human bronchoalveolar lavage fluid (BALF). We
      therefore conducted detailed investigations into the effects of extensive sample
      handling and sample preparation conditions on LPA levels in human BALF. Further,
      targeted lipid profiling of human BALF and plasma identified the most abundant
      lysophospholipids likely to interfere with LPA measurements. We present the
      findings from these investigations, highlighting the importance of well
      controlled sample handling for the accurate quantitation of LPA. Further, we show
      that chromatographic separation of individual LPA species from their
      corresponding lysophospholipid species is critical to avoid reporting
      artificially elevated levels. The optimized sample preparation and LC/MS/MS
      method was qualified using a stable isotope-labeled LPA as a surrogate calibrant
      and used to determine LPA levels in human BALF and plasma from a Phase 0 clinical
      study comparing idiopathic pulmonary fibrosis patients to healthy controls. 

PMID- 24872407
TI  - Syntaxin 8 modulates the post-synthetic trafficking of the TrkA receptor and
      inflammatory pain transmission.
AB  - Nerve growth factor (NGF) promotes the survival, maintenance, and neurite
      outgrowth of sensory and sympathetic neurons, and the effects are mediated by
      TrkA receptor signaling. Thus, the cell surface location of the TrkA receptor is
      crucial for NGF-mediated functions. However, the regulatory mechanism underlying
      TrkA cell surface levels remains incompletely understood. In this study, we
      identified syntaxin 8 (STX8), a Q-SNARE protein, as a novel TrkA-binding protein.
      Overexpression and knockdown studies showed that STX8 facilitates TrkA transport
      from the Golgi to the plasma membrane and regulates the surface levels of TrkA
      but not TrkB receptors. Furthermore, STX8 modulates downstream NGF-induced TrkA
      signaling and, consequently, the survival of NGF-dependent dorsal root ganglia
      neurons. Finally, knockdown of STX8 in rat dorsal root ganglia by recombinant
      adeno-associated virus serotype 6-mediated RNA interference led to analgesic
      effects on formalin-induced inflammatory pain. These findings demonstrate that
      STX8 is a modulator of TrkA cell surface levels and biological functions. 

PMID- 24872408
TI  - Internal ribosomal entry site (IRES) activity generates endogenous carboxyl
      terminal domains of Cx43 and is responsive to hypoxic conditions.
AB  - Connexin43 (Cx43) is the most abundant gap junction protein in higher vertebrate
      organisms and has been shown to be involved in junctional and non-junctional
      functions. In addition to the expression of full-length Cx43, endogenously
      produced carboxyl-terminal segments of Cx43 have been described and have been
      suggested to be involved in manifold biological functions, such as hypoxic
      preconditioning and neuronal migration. Molecular aspects, however, behind the
      separate generation of carboxyl-terminal segments of Cx43 have remained elusive.
      Here we report on a mechanism that may play a key role in the separate production
      of these domains. First, stringent evidence derived from siRNA treatment and
      specific knockouts revealed significant loss of the low molecular weight
      fragments of Cx43. By applying a dicistronic vector strategy on transfected cell
      lines, we were able to identify putative IRES activity (nucleotides 442-637) in
      the coding region of Cx43, which resides upstream from the nucleotide sequence
      encoding the carboxyl terminus (nucleotides 637-1149). Functional responsiveness
      of the endogenous expression of Cx43 fragments to hypoxic/ischemic treatment was
      evaluated in in vitro and in vivo models, which led to a significant increase of
      the fastest migrating form (20 kDa) under conditions of metabolic deprivation. By
      nano-MS spectrometry, we achieved stringent evidence of the identity of the 20
      kDa segment as part of the carboxyl-terminal domain of full-length Cx43. Our data
      prove the existence of endogenously expressed carboxyl-terminal domains, which
      may serve as valuable tools for further translational application in ischemic
      disorders.

PMID- 24872409
TI  - Phosphorylation of Rab5a protein by protein kinase Cepsilon is crucial for T-cell
      migration.
AB  - Rab GTPases control membrane traffic and receptor-mediated endocytosis. Within
      this context, Rab5a plays an important role in the spatial regulation of
      intracellular transport and signal transduction processes. Here, we report a
      previously uncharacterized role for Rab5a in the regulation of T-cell motility.
      We show that Rab5a physically associates with protein kinase Cepsilon
      (PKCepsilon) in migrating T-cells. After stimulation of T-cells through the
      integrin LFA-1 or the chemokine receptor CXCR4, Rab5a is phosphorylated on an N
      terminal Thr-7 site by PKCepsilon. Both Rab5a and PKCepsilon dynamically interact
      at the centrosomal region of migrating cells, and PKCepsilon-mediated
      phosphorylation on Thr-7 regulates Rab5a trafficking to the cell leading edge.
      Furthermore, we demonstrate that Rab5a Thr-7 phosphorylation is functionally
      necessary for Rac1 activation, actin rearrangement, and T-cell motility. We
      present a novel mechanism by which a PKCepsilon-Rab5a-Rac1 axis regulates
      cytoskeleton remodeling and T-cell migration, both of which are central for the
      adaptive immune response. 

PMID- 24872410
TI  - Rous sarcoma virus synaptic complex capable of concerted integration is
      kinetically trapped by human immunodeficiency virus integrase strand transfer
      inhibitors.
AB  - We determined conditions to produce milligram quantities of the soluble Rous
      sarcoma virus (RSV) synaptic complex that is kinetically trapped by HIV strand
      transfer inhibitors (STIs). Concerted integration catalyzed by RSV integrase (IN)
      is effectively inhibited by HIV STIs. Optimized assembly of the RSV synaptic
      complex required IN, a gain-of-function 3'-OH-recessed U3 oligonucleotide, and an
      STI under specific conditions to maintain solubility of the trapped synaptic
      complex at 4  degrees C. A C-terminal truncated IN (1-269 residues) produced a
      homogeneous population of trapped synaptic complex that eluted at ~ 151,000 Da
      upon Superdex 200 size-exclusion chromatography (SEC). Approximately 90% of input
      IN and DNA are incorporated into the trapped synaptic complex using either the C
      terminally truncated IN or wild type IN (1-286 residues). No STI is present in
      the SEC running buffer suggesting the STI-trapped synaptic complex is kinetically
      stabilized. The yield of the trapped synaptic complex correlates with the
      dissociative half-life of the STI observed with HIV IN-DNA complexes.
      Dolutegravir, MK-2048, and MK-0536 are equally effective, whereas raltegravir is
      ~ 70% as effective. Without an STI present in the assembly mixture, no trapped
      synaptic complex was observed. Fluorescence and mass spectroscopy analyses
      demonstrated that the STI remains associated with the trapped complex. SEC
      multiangle light scattering analyses demonstrated that wild type IN and the C
      terminal IN truncation are dimers that acted as precursors to the tetramer. The
      purified STI-trapped synaptic complex contained a tetramer as shown by cross
      linking studies. Structural studies of this three-domain RSV IN in complex with
      viral DNA may be feasible.

PMID- 24872412
TI  - The chemical uncoupler 2,4-dinitrophenol (DNP) protects against diet-induced
      obesity and improves energy homeostasis in mice at thermoneutrality.
AB  - The chemical uncoupler 2,4-dinitrophenol (DNP) was an effective and widely used
      weight loss drug in the early 1930s. However, the physiology of DNP has not been
      studied in detail because toxicity, including hyperthermia and death, reduced
      interest in the clinical use of chemical uncouplers. To investigate DNP action,
      mice fed a high fat diet and housed at 30  degrees C (to minimize facultative
      thermogenesis) were treated with 800 mg/liter DNP in drinking water. DNP
      treatment increased energy expenditure by ~ 17%, but did not change food intake.
      DNP-treated mice weighed 26% less than controls after 2 months of treatment due
      to decreased fat mass, without a change in lean mass. DNP improved glucose
      tolerance and reduced hepatic steatosis without observed toxicity. DNP treatment
      also reduced circulating T3 and T4 levels, Ucp1 expression, and brown adipose
      tissue activity, demonstrating that DNP-mediated heat generation substituted for
      brown adipose tissue thermogenesis. At 22  degrees C, a typical vivarium
      temperature that is below thermoneutrality, DNP treatment had no effect on body
      weight, adiposity, or glucose homeostasis. Thus, environmental temperature should
      be considered when assessing an anti-obesity drug in mice, particularly agents
      acting on energy expenditure. Furthermore, the beneficial effects of DNP suggest
      that chemical uncouplers deserve further investigation for the treatment of
      obesity and its comorbidities.

PMID- 24872411
TI  - Structure of REV-ERBbeta ligand-binding domain bound to a porphyrin antagonist.
AB  - REV-ERBalpha and REV-ERBbeta are members of the nuclear receptor (NR) superfamily
      of ligand-regulated transcription factors that play important roles in the
      regulation of circadian physiology, metabolism, and immune function. Although the
      REV-ERBs were originally characterized as orphan receptors, recent studies have
      demonstrated that they function as receptors for heme. Here, we demonstrate that
      cobalt protoporphyrin IX (CoPP) and zinc protoporphyrin IX (ZnPP) are ligands
      that bind directly to the REV-ERBs. However, instead of mimicking the agonist
      action of heme, CoPP and ZnPP function as antagonists of REV-ERB function. This
      was unexpected because the only distinction between these ligands is the metal
      ion that is coordinated. To understand the structural basis by which REV-ERBbeta
      can differentiate between a porphyrin agonist and antagonist, we characterized
      the interaction between REV-ERBbeta with heme, CoPP, and ZnPP using biochemical
      and structural approaches, including x-ray crystallography and NMR. The crystal
      structure of CoPP-bound REV-ERBbeta indicates only minor conformational changes
      induced by CoPP compared with heme, including the porphyrin ring of CoPP, which
      adopts a planar conformation as opposed to the puckered conformation observed in
      the heme-bound REV-ERBbeta crystal structure. Thus, subtle changes in the
      porphyrin metal center and ring conformation may influence the agonist versus
      antagonist action of porphyrins and when considered with other studies suggest
      that gas binding to the iron metal center heme may drive alterations in REV-ERB
      activity. 

PMID- 24872413
TI  - High mobility group nucleosomal binding domain 2 (HMGN2) SUMOylation by the SUMO
      E3 ligase PIAS1 decreases the binding affinity to nucleosome core particles.
AB  - High mobility group nucleosomal binding domain 2 (HMGN2) is a small and unique
      non-histone protein that has many functions in a variety of cellular processes,
      including regulation of chromatin structure, transcription, and DNA repair. In
      addition, it may have other roles in antimicrobial activity, cell homing, and
      regulating cytokine release. Although the biochemical properties of HMGN2 protein
      are regulated by acetylation and phosphorylation, it is not yet known whether
      HMGN2 activity can also be regulated by SUMOylation. In this study, we
      demonstrated for the first time that HMGN2 is modified by covalent attachment of
      small ubiquitin-related modifier 1 (SUMO1) by pro-inflammatory signal and
      identified the major SUMOylated lysine residues that localize to the HMGN2
      nucleosome-binding domain at Lys-17 and Lys-35. SENP1 can deSUMOylate SUMOylated
      HMGN2, and PIAS1 is the E3 ligase responsible for SUMOylation of HMGN2. Finally,
      using SUMO1-conjugated HMGN2 purified from a basal SUMOylation system in
      Escherichia coli, we demonstrated that SUMOylated HMGN2 has decreased the binding
      affinity to nucleosome core particles in comparison to unSUMOylated HMGN2. These
      observations potentially provide new perspectives for understanding the functions
      of HMGN2 in inflammatory reaction. 

PMID- 24872414
TI  - Phosphorylation of the transcription activator CLOCK regulates progression
      through a ~ 24-h feedback loop to influence the circadian period in Drosophila.
AB  - Circadian (? 24 h) clocks control daily rhythms in metabolism, physiology, and
      behavior in animals, plants, and microbes. In Drosophila, these clocks keep
      circadian time via transcriptional feedback loops in which clock-cycle (CLK-CYC)
      initiates transcription of period (per) and timeless (tim), accumulating levels
      of PER and TIM proteins feed back to inhibit CLK-CYC, and degradation of PER and
      TIM allows CLK-CYC to initiate the next cycle of transcription. The timing of key
      events in this feedback loop are controlled by, or coincide with, rhythms in PER
      and CLK phosphorylation, where PER and CLK phosphorylation is high during
      transcriptional repression. PER phosphorylation at specific sites controls its
      subcellular localization, activity, and stability, but comparatively little is
      known about the identity and function of CLK phosphorylation sites. Here we
      identify eight CLK phosphorylation sites via mass spectrometry and determine how
      phosphorylation at these sites impacts behavioral and molecular rhythms by
      transgenic rescue of a new Clk null mutant. Eliminating phosphorylation at four
      of these sites accelerates the feedback loop to shorten the circadian period,
      whereas loss of CLK phosphorylation at serine 859 increases CLK activity, thereby
      increasing PER levels and accelerating transcriptional repression. These results
      demonstrate that CLK phosphorylation influences the circadian period by
      regulating CLK activity and progression through the feedback loop.

PMID- 24872415
TI  - N-glycosylation of asparagine 8 regulates surface expression of major
      histocompatibility complex class I chain-related protein A (MICA) alleles
      dependent on threonine 24.
AB  - NKG2D is an activating receptor expressed on several types of human lymphocytes.
      NKG2D ligands can be induced upon cell stress and are frequently targeted post
      translationally in infected or transformed cells to avoid immune recognition.
      Virus infection and inflammation alter protein N-glycosylation, and we have
      previously shown that changes in cellular N-glycosylation are involved in
      regulation of NKG2D ligand surface expression. The specific mode of regulation
      through N-glycosylation is, however, unknown. Here we investigated whether direct
      N-glycosylation of the NKG2D ligand MICA itself is critical for cell surface
      expression and sought to identify the essential residues. We found that a single
      N-glycosylation site (Asn(8)) was important for MICA018 surface expression. The
      frequently expressed MICA allele 008, with an altered transmembrane and
      intracellular domain, was not affected by mutation of this N-glycosylation site.
      Mutational analysis revealed that a single amino acid (Thr(24)) in the
      extracellular domain of MICA018 was essential for the N-glycosylation dependence,
      whereas the intracellular domain was not involved. The HHV7 immunoevasin, U21,
      was found to inhibit MICA018 surface expression by affecting N-glycosylation, and
      the retention was rescued by T24A substitution. Our study reveals N-glycosylation
      as an allele-specific regulatory mechanism important for regulation of surface
      expression of MICA018, and we pinpoint the residues essential for this N
      glycosylation dependence. In addition, we show that this regulatory mechanism of
      MICA surface expression is likely targeted during different pathological
      conditions. 

PMID- 24872416
TI  - Interferon regulatory factor 6 differentially regulates Toll-like receptor 2
      dependent chemokine gene expression in epithelial cells.
AB  - Epidermal and mucosal epithelial cells are integral to host defense. They not
      only act as a physical barrier but also utilize pattern recognition receptors,
      such as the Toll-like receptors (TLRs), to detect and respond to pathogens.
      Members of the interferon regulatory factor (IRF) family of transcription factors
      are key components of TLR signaling as they impart specificity to downstream
      responses. Although IRF6 is a critical regulator of epithelial cell proliferation
      and differentiation, its role in TLR signaling has not previously been addressed.
      We show here that IRF6 is activated by IRAK1 as well as by MyD88 but not by TRIF
      or TBK1. Co-immunoprecipitation experiments further demonstrated that IRF6 can
      interact with IRAK1. Gene silencing in epithelial cells along with gene promoter
      reporter assays showed that IRAK1 mediates TLR2-inducible CCL5 gene expression at
      least in part by promoting IRF6 activation. Conversely, IRAK1 regulated CXCL8
      gene expression independently of IRF6, thus identifying a molecular mechanism by
      which TLR2 signaling differentially regulates the expression of specific
      chemokines in epithelial cells. Bioinformatics analysis and mutagenesis-based
      experiments identified Ser-413 and Ser-424 as key regulatory sites in IRF6.
      Phosphomimetic mutation of these residues resulted in greatly enhanced IRF6
      dimerization and trans-activator function. Collectively, our findings suggest
      that, in addition to its importance for epithelial barrier function, IRF6 also
      contributes to host defense by providing specificity to the regulation of
      inflammatory chemokine expression by TLR2 in epithelial cells. 

PMID- 24872418
TI  - The polypeptide transport-associated (POTRA) domains of TpsB transporters
      determine the system specificity of two-partner secretion systems.
AB  - The two-partner secretion (TPS) systems of Gram-negative bacteria secrete large
      TpsA exoproteins by a dedicated TpsB transporter in the outer membrane. TpsBs
      contain an N-terminal module located in the periplasm that includes two
      polypeptide transport-associated (POTRA) domains. These are thought to initiate
      secretion of a TpsA by binding its N-terminal secretion signal, called the TPS
      domain. Neisseria meningitidis encodes up to five TpsA proteins that are secreted
      via only two TpsB transporters: TpsB1 and TpsB2. Of these two, the TpsB2
      recognizes the TPS domains of all TpsAs, despite their sequence diversity. By
      contrast, the TpsB1 shows a limited recognition of a TPS domain that is shared by
      two TpsAs. The difference in substrate specificity of the TpsBs enabled us to
      investigate the role of the POTRA domains in the selection of TPS domains. We
      tested secretion of TPS domains or full-length TpsAs by TpsB mutants with
      deleted, duplicated, and exchanged POTRA domains. Exchanging the two POTRA
      domains of a TpsB resulted in a switch in specificity. Furthermore, exchanging a
      single POTRA domain showed that each of the two domains contributed to the cargo
      selection. Remarkably, the order of the POTRA domains could be reversed without
      affecting substrate selection, but this aberrant order did result in an
      alternatively processed secretion product. Our results suggest that secretion of
      a TpsA is initiated by engaging both POTRA domains of a TpsB transporter and that
      these select the cognate TpsAs for secretion. 

PMID- 24872417
TI  - Phosphorylation of cyclin-dependent kinase 5 (Cdk5) at Tyr-15 is inhibited by
      Cdk5 activators and does not contribute to the activation of Cdk5.
AB  - Cdk5 is a member of the cyclin-dependent kinase (Cdk) family. In contrast to
      other Cdks that promote cell proliferation, Cdk5 plays a role in regulating
      various neuronal functions, including neuronal migration, synaptic activity, and
      neuron death. Cdks responsible for cell proliferation need phosphorylation in the
      activation loop for activation in addition to binding a regulatory subunit
      cyclin. Cdk5, however, is activated only by binding to its activator, p35 or p39.
      Furthermore, in contrast to Cdk1 and Cdk2, which are inhibited by phosphorylation
      at Tyr-15, the kinase activity of Cdk5 is reported to be stimulated when
      phosphorylated at Tyr-15 by Src family kinases or receptor-type tyrosine kinases.
      We investigated the activation mechanism of Cdk5 by phosphorylation at Tyr-15.
      Unexpectedly, however, it was found that Tyr-15 phosphorylation occurred only on
      monomeric Cdk5, and the coexpression of activators, p35/p25, p39, or Cyclin I,
      inhibited the phosphorylation. In neuron cultures, too, the activation of Fyn
      tyrosine kinase did not increase Tyr-15 phosphorylation of Cdk5. Further, phospho
      Cdk5 at Tyr-15 was not detected in the p35-bound Cdk5. In contrast, expression of
      active Fyn increased p35 in neurons. These results indicate that phosphorylation
      at Tyr-15 is not an activation mechanism of Cdk5 but, rather, indicate that
      tyrosine kinases could activate Cdk5 by increasing the protein amount of p35.
      These results call for reinvestigation of how Cdk5 is regulated downstream of Src
      family kinases or receptor tyrosine kinases in neurons, which is an important
      signaling cascade in a variety of neuronal activities. 

PMID- 24872419
TI  - Mesotrypsin and caspase-14 participate in prosaposin processing: potential
      relevance to epidermal permeability barrier formation.
AB  - A proteomics-based search for molecules interacting with caspase-14 identified
      prosaposin and epidermal mesotrypsin as candidates. Prosaposin is a precursor of
      four sphingolipid activator proteins (saposins A-D) that are essential for
      lysosomal hydrolysis of sphingolipids. Thus, we hypothesized that caspase-14 and
      mesotrypsin participate in processing of prosaposin. Because we identified a
      saposin A sequence as an interactor with these proteases, we prepared a specific
      antibody to saposin A and focused on saposin A-related physiological reactions.
      We found that mesotrypsin generated saposins A-D from prosaposin, and mature
      caspase-14 contributed to this process by activating mesotrypsinogen to
      mesotrypsin. Knockdown of these proteases markedly down-regulated saposin A
      synthesis in skin equivalent models. Saposin A was localized in granular cells,
      whereas prosaposin was present in the upper layer of human epidermis. The
      proximity ligation assay confirmed interaction between prosaposin, caspase-14,
      and mesotrypsin in the granular layer. Oil Red staining showed that the lipid
      envelope was significantly reduced in the cornified layer of skin from saposin A
      deficient mice. Ultrastructural studies revealed severely disorganized cornified
      layer structure in both prosaposin- and saposin A-deficient mice. Overall, our
      results indicate that epidermal mesotrypsin and caspase-14 work cooperatively in
      prosaposin processing. We propose that they thereby contribute to permeability
      barrier formation in vivo. 

PMID- 24872423
TI  - Massifquant: open-source Kalman filter-based XC-MS isotope trace feature
      detection.
AB  - MOTIVATION: Isotope trace (IT) detection is a fundamental step for liquid or gas
      chromatography mass spectrometry (XC-MS) data analysis that faces a multitude of
      technical challenges on complex samples. The Kalman filter (KF) application to IT
      detection addresses some of these challenges; it discriminates closely eluting
      ITs in the m/z dimension, flexibly handles heteroscedastic m/z variances and does
      not bin the m/z axis. Yet, the behavior of this KF application has not been fully
      characterized, as no cost-free open-source implementation exists and incomplete
      evaluation standards for IT detection persist. RESULTS: Massifquant is an open
      source solution for KF IT detection that has been subjected to novel and rigorous
      methods of performance evaluation. The presented evaluation with accompanying
      annotations and optimization guide sets a new standard for comparative IT
      detection. Compared with centWave, matchedFilter and MZMine2-alternative IT
      detection engines-Massifquant detected more true ITs in a real LC-MS complex
      sample, especially low-intensity ITs. It also offers competitive specificity and
      equally effective quantitation accuracy. AVAILABILITY AND IMPLEMENTATION:
      Massifquant is integrated into XCMS with GPL license >= 2.0 and hosted by
      Bioconductor: http://bioconductor.org. Annotation data are archived at
      http://hdl.lib.byu.edu/1877/3232. Parameter optimization code and documentation
      is hosted at https://github.com/topherconley/optimize-it.

PMID- 24872422
TI  - MPBind: a Meta-motif-based statistical framework and pipeline to Predict Binding
      potential of SELEX-derived aptamers.
AB  - Aptamers are 'synthetic antibodies' that can bind to target molecules with high
      affinity and specificity. Aptamers are chemically synthesized and their discovery
      can be performed completely in vitro, rather than relying on in vivo biological
      processes, making them well-suited for high-throughput discovery. However, a
      large fraction of the most enriched aptamers in Systematic Evolution of Ligands
      by EXponential enrichment (SELEX) rounds display poor binding activity. Here, we
      present MPBind, a Meta-motif-based statistical framework and pipeline to Predict
      the BIND: ing potential of SELEX-derived aptamers. Using human embryonic stem
      cell SELEX-Seq data, MPBind achieved high prediction accuracy for binding
      potential. Further analysis showed that MPBind is robust to both polymerase chain
      reaction amplification bias and incomplete sequencing of aptamer pools. These two
      biases usually confound aptamer analysis. AVAILABILITY AND IMPLEMENTATION: MPBind
      software and documents are available at http://www.morgridge.net/MPBind.html. The
      human embryonic stem cells whole-cell SELEX-Seq data are available at
      http://www.morgridge.net/Aptamer/.

PMID- 24872420
TI  - HIV-1 envelope proteins and V1/V2 domain scaffolds with mannose-5 to improve the
      magnitude and quality of protective antibody responses to HIV-1.
AB  - Two lines of investigation have highlighted the importance of antibodies to the
      V1/V2 domain of gp120 in providing protection from HIV-1 infection. First, the
      recent RV144 HIV-1 vaccine trial documented a correlation between non
      neutralizing antibodies to the V2 domain and protection. Second, multiple broadly
      neutralizing monoclonal antibodies to the V1/V2 domain (e.g. PG9) have been
      isolated from rare infected individuals, termed elite neutralizers.
      Interestingly, the binding of both types of antibodies appears to depend on the
      same cluster of amino acids (positions 167-171) adjacent to the junction of the B
      and C strands of the four-stranded V1/V2 domain beta-sheet structure. However,
      the broadly neutralizing mAb, PG9, additionally depends on mannose-5 glycans at
      positions 156 and 160 for binding. Because the gp120 vaccine immunogens used in
      previous HIV-1 vaccine trials were enriched for complex sialic acid-containing
      glycans, and lacked the high mannose structures required for the binding of PG9
      like mAbs, we wondered if these immunogens could be improved by limiting
      glycosylation to mannose-5 glycans. Here, we describe the PG9 binding activity of
      monomeric gp120s from multiple strains of HIV-1 produced with mannose-5 glycans.
      We also describe the properties of glycopeptide scaffolds from the V1/V2 domain
      also expressed with mannose-5 glycans. The V1/V2 scaffold from the A244 isolate
      was able to bind the PG9, CH01, and CH03 mAbs with high affinity provided that
      the proper glycans were present. We further show that immunization with A244
      V1/V2 fragments alone, or in a prime/boost regimen with gp120, enhanced the
      antibody response to sequences in the V1/V2 domain associated with protection in
      the RV144 trial.

PMID- 24872421
TI  - Regulated intramembrane proteolysis of the frontotemporal lobar degeneration risk
      factor, TMEM106B, by signal peptide peptidase-like 2a (SPPL2a).
AB  - The sequential processing of single pass transmembrane proteins via ectodomain
      shedding followed by intramembrane proteolysis is involved in a wide variety of
      signaling processes, as well as maintenance of membrane protein homeostasis. Here
      we report that the recently identified frontotemporal lobar degeneration risk
      factor TMEM106B undergoes regulated intramembrane proteolysis. We demonstrate
      that TMEM106B is readily processed to an N-terminal fragment containing the
      transmembrane and intracellular domains, and this processing is dependent on the
      activities of lysosomal proteases. The N-terminal fragment is further processed
      into a small, rapidly degraded intracellular domain. The GxGD aspartyl proteases
      SPPL2a and, to a lesser extent, SPPL2b are responsible for this intramembrane
      cleavage event. Additionally, the TMEM106B paralog TMEM106A is also lysosomally
      localized; however, it is not a specific substrate of SPPL2a or SPPL2b. Our data
      add to the growing list of proteins that undergo intramembrane proteolysis and
      may shed light on the regulation of the frontotemporal lobar degeneration risk
      factor TMEM106B. 

PMID- 24872424
TI  - CODOC: efficient access, analysis and compression of depth of coverage signals.
AB  - Current data formats for the representation of depth of coverage data (DOC), a
      central resource for interpreting, filtering or detecting novel features in high
      throughput sequencing datasets, were primarily designed for visualization
      purposes. This limits their applicability in stand-alone analyses of these data,
      mainly owing to inaccurate representation or mediocre data compression. CODOC is
      a novel data format and comprehensive application programming interface for
      efficient representation, access and analysis of DOC data. CODOC compresses these
      data ~ 4-32* better than the best current comparable method by exploiting
      specific data characteristics while at the same time enabling more-exact signal
      recovery for lossy compression and very fast query answering times. AVAILABILITY
      AND IMPLEMENTATION: Java source code and binaries are freely available for non
      commercial use at http://purl.org/bgraph/codoc.

PMID- 24872425
TI  - AlphaMPSim: flexible simulation of multi-parent crosses.
AB  - Multi-parent crosses of recombinant inbred lines exist in many species for fine
      scale analysis of genome structure and marker-trait association. These
      populations encompass a wide range of crossing designs with varying potential.
      AlphaMPSim is a flexible simulation program that is efficiently designed for
      comparison of alternative designs for traits with varying genetic architectures
      and biallelic markers with densities up to full sequence. A large pool of founder
      haplotypes can be supplied by the user, or generated via integration with
      external coalescent simulation programs such as MaCS. From these, diverse
      founders for multi-parent designs can be generated automatically, and users can
      compare designs generated from diverse pedigrees. Full tracking of identity by
      descent status of alleles within the pedigree is undertaken, and output files are
      compatible with commonly available analysis packages in R. AVAILABILITY AND
      IMPLEMENTATION: Executable versions of AlphaMPSim for Mac and Linux and a user
      manual are available at http://www.roslin.ed.ac.uk/john-hickey/software
      packages/.

PMID- 24872426
TI  - MoDPepInt: an interactive web server for prediction of modular domain-peptide
      interactions.
AB  - MoDPepInt (Modular Domain Peptide Interaction) is a new easy-to-use web server
      for the prediction of binding partners for modular protein domains. Currently, we
      offer models for SH2, SH3 and PDZ domains via the tools SH2PepInt, SH3PepInt and
      PDZPepInt, respectively. More specifically, our server offers predictions for 51
      SH2 human domains and 69 SH3 human domains via single domain models, and
      predictions for 226 PDZ domains across several species, via 43 multidomain
      models. All models are based on support vector machines with different kernel
      functions ranging from polynomial, to Gaussian, to advanced graph kernels. In
      this way, we model non-linear interactions between amino acid residues. Results
      were validated on manually curated datasets achieving competitive performance
      against various state-of-the-art approaches. AVAILABILITY AND IMPLEMENTATION: The
      MoDPepInt server is available under the URL http://modpepint.informatik.uni
      freiburg.de/.

PMID- 24872428
TI  - GADD45 proteins: roles in cellular senescence and tumor development.
AB  - The growth arrest and DNA damage 45 (GADD45) family genes regulate DNA repair,
      cell cycle, cell survival, apoptosis, senescence, and DNA demethylation in the
      cells under various stress stimuli, such as oxidative stress, UV radiation, and
      oncogenic stress. Recent studies have provided important insights regarding how
      different oncogenic stresses activate GADD45 signaling pathway and lead to
      disparate influences on tumor initiation. In this review, we discuss the
      deregulation and cellular function of GADD45 proteins in the context of cancer
      development. We also highlight recent advances in exploring the tumor suppressive
      function of GADD45 proteins-triggered cellular senescence.

PMID- 24872427
TI  - DualAligner: a dual alignment-based strategy to align protein interaction
      networks.
AB  - MOTIVATION: Given the growth of large-scale protein-protein interaction (PPI)
      networks obtained across multiple species and conditions, network alignment is
      now an important research problem. Network alignment performs comparative
      analysis across multiple PPI networks to understand their connections and
      relationships. However, PPI data in high-throughput experiments still suffer from
      significant false-positive and false-negatives rates. Consequently, high
      confidence network alignment across entire PPI networks is not possible. At best,
      local network alignment attempts to alleviate this problem by completely ignoring
      low-confidence mappings; global network alignment, on the other hand, pairs all
      proteins regardless. To this end, we propose an alternative strategy: instead of
      full alignment across the entire network or completely ignoring low-confidence
      regions, we aim to perform highly specific protein-to-protein alignments where
      data confidence is high, and fall back on broader functional region-to-region
      alignment where detailed protein-protein alignment cannot be ascertained. The
      basic idea is to provide an alignment of multiple granularities to allow
      biological predictions at varying specificity. RESULTS: DualAligner performs dual
      network alignment, in which both region-to-region alignment, where whole subgraph
      of one network is aligned to subgraph of another, and protein-to-protein
      alignment, where individual proteins in networks are aligned to one another, are
      performed to achieve higher accuracy network alignments. Dual network alignment
      is achieved in DualAligner via background information provided by a combination
      of Gene Ontology annotation information and protein interaction network data. We
      tested DualAligner on the global networks from IntAct and demonstrated the
      superiority of our approach compared with state-of-the-art network alignment
      methods. We studied the effects of parameters in DualAligner in controlling the
      quality of the alignment. We also performed a case study that illustrates the
      utility of our approach. AVAILABILITY AND IMPLEMENTATION:
      http://www.cais.ntu.edu.sg/~assourav/DualAligner/.

PMID- 24872429
TI  - Impact of diet-induced obesity in male mouse reproductive system: The role of
      advanced glycation end product-receptor for advanced glycation end product axis.
AB  - Obesity represents a route to broad physiological dysfunction affecting major
      organs including male urogenital system. Hyperglycemia, hyperlipidemia, and
      oxidative stress associated with obesity augment the formation of reactive
      metabolic by-products, namely advanced glycation end products (AGEs), leading to
      increased tissue deposition and damage. The exogenous intake and the endogenous
      accumulation of AGEs contribute to metabolic and reproductive abnormalities in
      both women and men. The present study assessed the effects of a diet high in
      saturated fatty acids (SAFA) on the lipid and metabolic profile (AGE levels,
      oxidative stress) as well as pathogenic (AGE, receptor for AGEs [RAGE]
      expression, apoptosis) and morphometric parameters of male reproductive system in
      vivo. Effects of switching to a diet rich in monounsaturated fatty acids (MUFA)
      or equal in the proportion MUFA to SAFA were further investigated. SAFA-fed
      animals were characterized by increased serum lipid concentrations (p < .05)
      compared to controls, but AGEs and peroxide levels were not significantly
      different across the different experimental groups. Elevated AGE deposition was
      detected for the first time in germ cells with a higher staining intensity in
      animals on the SAFA diet, compared to MUFA or MUFA-SAFA-fed animals or the
      control samples (p = .018). In Leydig cells, AGE localization was higher in the
      entire cohort of high-fat-fed animals compared to controls (p < .05). High-fat
      fed mice displayed enhanced apoptosis compared to controls (p < .005).
      Furthermore, prostatic tissue demonstrated reduction in epithelial folding, an
      effect which was significantly reversed after MUFA diet administration. Our
      findings provide the basis for further investigation of AGE-RAGE axis in
      testicular and prostatic disturbances associated with diet-induced obesity.
      Simple dietetic intervention has beneficial effects on metabolic dysfunction of
      reproductive system before overt manifestations, indicating glycation as a
      promising therapeutic target.

PMID- 24872430
TI  - In vitro enzyme-mimic activity and in vivo therapeutic potential of HSJ-0017, a
      novel Mn porphyrin-based antioxidant enzyme mimic.
AB  - Manganese (III) 5, 10, 15, 20-tetrakis [3-(2-(2-methoxy)-ethoxy) ethoxy] phenyl
      porphyrin chloride, designated HSJ-0017, is a novel antioxidant enzyme mimic. The
      aim of the present study was to investigate the enzyme-mimic activity and the
      therapeutic potential of HSJ-0017 in free radical-related diseases. Superoxide
      dismutase (SOD) mimic activity was measured by the nitroblue tetrazolium chloride
      monohydrate reduction assay. Catalase (CAT) mimic activity was measured based on
      the decomposition of hydrogen peroxide. The antitumor, radioprotective and
      chemoprotective effects of HSJ-0017 were evaluated in H22 or S180 tumor-bearing
      Kunming mice. The anti-inflammatory and hepatoprotective effects were,
      respectively, evaluated in histamine-induced edema model and CCl4-induced hepatic
      damage model in Wistar rats. HSJ-0017 over a concentration range of 0.001-10
      umol/L significantly inhibited the generation of superoxide anion. Significant
      hydrogen peroxide scavenging activity was observed when the concentration of HSJ
      0017 was higher than 0.01 umol/L. HSJ-0017 at a dose of 3.0 mg/kg exhibited
      significant antitumor effect on S180 tumor xenografts, whereas no significant
      antitumor effect was observed in H22 tumor xenografts. HSJ-0017 at a dose of 3.0
      mg/kg enhanced the antitumor effects of radiotherapy and chemotherapy, and
      reduced their toxicity. However, HSJ-0017 counteracted the antitumor effects of
      radiotherapy when administered simultaneously with radiotherapy. HSJ-0017 showed
      significant anti-inflammatory and hepatoprotective effects. Our results
      demonstrate that HSJ-0017 exhibits antioxidant, antitumor, anti-inflammatory,
      radioprotective, chemoprotective, and hepatoprotective effects. It is a potent
      dual SOD/CAT mimic.

PMID- 24872431
TI  - Endostar, a novel human recombinant endostatin, attenuates liver fibrosis in CCl4
      induced mice.
AB  - Decreasing hepatic fibrosis remains one of the major therapeutic challenges in
      hepatology. The present study aims to evaluate the effect of Endostar on both
      CCl4-induced liver fibrosis in mice and a hepatic stellate cell (HSC) line. Two
      main models were studied: (i) a liver fibrosis model was induced in BALB/c mice
      using CCl4 by intraperitoneal injection for six weeks. Six animal groups were
      studied: group 1: normal animals; group 2: CCl4-induced liver fibrosis; group 3:
      CCl4 + Endostar 20 mg/kg/d, six weeks; group 4: CCl4 + Endostar 10 mg/kg/d, six
      weeks; group 5: CCl4 + Endostar 20 mg/kg/d, four weeks; group 6: CCl4 + Endostar
      10 mg/kg/d, four weeks corresponded to different Endostar doses and duration of
      administration. Liver fibrosis was evaluated by histopathological staining and
      liver hydroxyproline content. Expressions of collagen type I, alpha-smooth muscle
      actin (alpha-SMA), TGF-beta1 and VEGFR were measured by real-time polymerase
      chain reaction (PCR). (ii) A liver cell model. HSC-T6 cells were cultured with or
      without Endostar for 12 h or 24 h. Expressions of collagen type I, alpha-SMA, and
      TGF-beta1 were measured by real-time PCR. Collagen I and transforming growth
      factor beta1 (TGF-beta1) contents in cell supernatant were measured by enzyme
      linked immunosorbent assay. As compared to the group without Endostar, liver
      fibrosis scores and hydroxyproline content were decreased in both Endostar groups
      (P < 0.05). Moreover, Endostar inhibited the hepatic expression of alpha-SMA, TGF
      beta1, Collagen-1, VEGFR1, and VEGFR2 mRNA (P < 0.05). In the HSC-T6 cell line
      model, Endostar profoundly inhibited the expression of alpha-SMA, Collagen-1, and
      TGF-beta1 mRNA. Expressions of Collagen-1 and TGF-beta1 protein were decreased in
      the Endostar group as compared to the normal controls in the supernatant of HSC
      T6 cells (P < 0.05). Endostar decreased both liver fibrosis in CCl4-induced mice
      and collagen synthesis in HSCs in vitro. Therefore, this recombinant human
      endostatin is a promising compound for counteracting liver fibrosis.

PMID- 24872433
TI  - Protective effects of melittin on tumor necrosis factor-alpha induced hepatic
      damage through suppression of apoptotic pathway and nuclear factor-kappa B
      activation.
AB  - Melittin, a major polypeptide in honeybee venom, have been used to treat
      inflammatory disease. Various studies have demonstrated the anti-bacterial, anti
      viral, anti-inflammatory and anticancer effects of bee venom and melittin.
      However, the precise mechanism of melittin in liver disease is not yet known.
      Apoptosis contributes to liver inflammation and fibrosis. Knowledge of the
      apoptotic mechanisms is important to develop new and effective therapies for
      treatment of cirrhosis. In the present study, we investigated the anti-apoptotic
      effect of melittin on tumor necrosis factor (TNF)-alpha/actinomycin (Act) D
      induced apoptosis in hepatocytes. Our results show significant protection from
      DNA damage by melittin treatment compared with corresponding TNF-alpha/Act D
      treated hepatocytes without melittin. Melittin inhibited TNF-alpha/Act D-induced
      activation of the caspase, bcl-2 family of proteins and poly ADP-ribose
      polymerase (PARP)-1. Our results also indicate that melittin decreased nuclear
      factor-kappa B (NF-kappaB) by degradation of phosphorylation of IkappaB kinase (p
      IKK) and NF-kappaB DNA binding activity in TNF-alpha/Act D-treated hepatocytes.
      These results suggest that melittin possesses a potent suppressive effect on
      apoptotic responses in TNF-alpha/Act D-treated hepatocytes via the NF-kappaB
      pathway. 

PMID- 24872432
TI  - Genistein supplementation increases bone turnover but does not prevent alcohol
      induced bone loss in male mice.
AB  - Chronic alcohol consumption results in bone loss through increased bone
      resorption and decreased bone formation. These effects can be reversed by
      estradiol (E2) supplementation. Soy diets are suggested to have protective
      effects on bone loss in men and women, as a result of the presence of soy protein
      associated phytoestrogens such as genistein (GEN). In this study, male mice were
      pair-fed (PF), a control diet, an ethanol (EtOH) diet, or EtOH diet supplemented
      with 250 mg/kg of GEN for 8 weeks to test if GEN protects against bone loss
      associated with chronic drinking. Interestingly, alcohol consumption reduced
      cortical area and thickness and trabecular bone volume in both EtOH and EtOH/GEN
      groups when compared to the corresponding PF and PF/GEN controls, P < 0.05.
      However, in the trabecular bone compartment, we observed a significant increase
      in overall trabecular bone density in the PF/GEN group compared to the PF
      controls. Bone loss in the EtOH-treated mice was associated with the inhibition
      of osteoblastogenesis as indicated by decreased alkaline phosphatase staining in
      ex vivo bone marrow cultures, P < 0.05. GEN supplementation improved
      osteoblastogenesis in the EtOH/GEN cultures compared to the EtOH group, P < 0.05.
      Vertebral expression of bone-formation markers, osteocalcin, and runt-related
      transcription factor 2 (Runx2) was also significantly up-regulated in the PF/GEN
      and EtOH/GEN groups compared to the PF and EtOH-treated groups. GEN
      supplementation also increased the expression of receptor activator of nuclear
      factor kappa-B ligand (RANKL) in the PF/GEN, an increase that persisted in the
      EtOH/GEN-treated animals (P < 0.05), and increased basal hydrogen peroxide
      production and RANKL mRNA expression in primary bone marrow cultures in vitro, P
      < 0.05. These findings suggest that GEN supplementation increases the overall
      bone remodeling and, in the context of chronic alcohol consumption, does not
      protect against the oxidative stress-associated EtOH-mediated bone resorption.

PMID- 24872434
TI  - Cardiac sympathetic afferent reflex response to intermedin microinjection into
      paraventricular nucleus is mediated by nitric oxide and gamma-amino butyric acid
      in hypertensive rats.
AB  - Intermedin (IMD) is a member of calcitonin/calcitonin gene-related peptide (CGRP)
      and involves in the regulation of cardiovascular function in both peripheral
      tissues and central nervous system (CNS). Paraventricular nucleus (PVN) of
      hypothalamus is an important site in the control of cardiac sympathetic afferent
      reflex (CSAR) which participates in sympathetic over-excitation of hypertension.
      The aim of this study is to investigate whether IMD in the PVN is involved in the
      inhibition of CSAR and its related mechanism in hypertension. Rats were subjected
      to two-kidney one-clip (2K1C) surgery to induce renovascular hypertension or sham
      operation (Sham). Acute experiments were carried out four weeks later under
      anesthesia. The CSAR was evaluated with the renal sympathetic nerve activity
      (RSNA) and mean arterial pressure (MAP) responses to the epicardial application
      of capsaicin. The RSNA and MAP were recorded in sinoaortic-denervated, cervical
      vagotomized and anesthetized rats. Bilateral PVN microinjection of IMD (25 pmol)
      caused greater decrease in the CSAR in 2K1C rats than in Sham rats, which was
      prevented by pretreatment with adrenomedullin (AM) receptor antagonist AM22-52,
      non-selective nitric oxide (NO) synthase (NOS) inhibitor L-NAME or gamma-amino
      butyric acid (GABA)B receptor blocker CGP-35348. PVN pretreatment with CGRP
      receptor antagonist CGRP8-37 or GABA(A) receptor blocker gabazine had no
      significant effect on the CSAR response to IMD. AM22-52, L-NAME and CGP-35348 in
      the PVN could increase CSAR in Sham and 2K1C rats. These data indicate that IMD
      in the PVN inhibits CSAR via AM receptor, and both NO and GABA in the PVN involve
      in the effect of IMD on CSAR in Sham and renovascular hypertensive rats.

PMID- 24872435
TI  - Evaluation of antibody-chemokine fusion proteins for tumor-targeting
      applications.
AB  - There is an increasing biotechnological interest in the 'arming' of therapeutic
      antibodies with bioactive payloads. While many antibody-cytokine fusion proteins
      have been extensively investigated in preclinical and clinical studies, there are
      only few reports related to antibody-chemokine fusion proteins
      ('immunochemokines'). Here, we describe the cloning, expression, and
      characterization of 10 immunochemokines based on the monoclonal antibody F8,
      specific to the alternatively spliced extra domain A (EDA) of fibronectin, a
      marker of angiogenesis. Among the 10 murine chemokines tested in our study, only
      CCL19, CCL20, CCL21, and CXCL10 could be expressed and isolated at acceptable
      purity levels as F8-based fusion proteins. The immunochemokines retained the
      binding characteristics of the parental antibody, but could not be characterized
      by gel-filtration analysis, an analytical limitation which had previously been
      observed in our laboratory for the unconjugated chemokines. When radioiodinated
      preparations of CCL19-F8, CCL20-F8, CCL21-F8, and CXCL10-F8 were tested in
      quantitative biodistribution studies in tumor-bearing mice, the four fusion
      proteins failed to preferentially accumulate at the tumor site, while the
      unconjugated parental antibody displayed a tumor:blood ratio >20:1, 24 h after
      intravenous (i.v.) administration. The tumor-targeting ability of CCL19-F8 could
      be rescued only in part by preadministration of unlabeled CCL19-F8, indicating
      that a chemokine trapping mechanism may hinder pharmacodelivery strategies. While
      this article highlights expression, analytical, and biodistribution challenges
      associated with the antibody-based in vivo delivery of chemokines at sites of
      disease, it provides the first comprehensive report in this field and may
      facilitate future studies with immunochemokines.

PMID- 24872436
TI  - A single low dose of cadmium exposure induces benign prostate hyperplasia like
      condition in rat: A novel benign prostate hyperplasia rodent model.
AB  - Abnormal prostate growth is the most prevalent pathological sign in aged human
      males, as reflected by high incidence of benign prostate hyperplasia (BPH) and
      prostate cancer. In spite of the high prevalence, the etiology and
      pathophysiology of BPH is unclear due to the lack of any established rodent model
      for study. It has been demonstrated that the cadmium (Cd) mimics the activity of
      androgen or estrogen by interacting with the steroid hormone receptors in the
      prostate and elicits BPH, but the specific receptor which binds to Cd is still
      unknown. Our lab studies with BPH patients highlighted a strong co-relation
      between smokings with increased Cd content. Changes in the maximum urinary flow
      rate (Qmax) and prostatic acid phosphatase (PAP) level further supports that Cd
      can induce BPH like condition. Therefore, the present study was aimed to induce
      BPH like condition in rats by Cd administration. The dose of cadmium was
      standardized in an age- and time-dependent manner, which was further examined by
      prostate weight, histology, and PAP levels that elucidated the pathogenesis of
      BPH. Further to understand the molecular basis, steroid hormone receptor
      antagonist experiment was performed. Gene expression and immunohistochemistry
      data suggest that Cd induces hyperplasia like condition by activating the
      androgen receptor and estrogen receptor-alpha and suppresses the action of
      estrogen receptor-beta. The experimental model used here is a cost effective,
      less time consuming and potentially valuable tool for investigating the
      respective functions of epithelial and stromal hormone receptors. The
      applicability of this model would be helpful in understanding the pathogenesis of
      BPH and its progression.

PMID- 24872437
TI  - Acute radiation enteritis caused by dose-dependent radiation exposure in dogs:
      experimental research.
AB  - Accidental or intended radiation exposure in mass casualty settings presents a
      serious and on-going threat. The development of mitigating and treating agents
      requires appropriate animal models. Unfortunately, the majority of research on
      radiation enteritis in animals has lacked specific assessments and targeted
      therapy. Our study showed beagle dogs, treated by intensity-modulated radiation
      therapy (IMRT) for abdominal irradiation, were administered single X-ray doses of
      8-30 Gy. The degree of intestinal tract injury for all of the animals after
      radiation exposure was evaluated with regard to clinical syndrome, endoscopic
      findings, histological features, and intestinal function. The range of single
      doses (8 Gy, 10-14 Gy, and 16-30 Gy) represented the degree of injury (mild,
      moderate, and severe, respectively). Acute radiation enteritis included clinical
      syndrome with fever, vomiting, diarrhea, hemafecia, and weight loss; typical
      endoscopic findings included edema, bleeding, mucosal abrasions, and ulcers; and
      intestinal biopsy results revealed mucosal necrosis, erosion, and loss,
      inflammatory cell infiltration, hemorrhage, and congestion. Changes in serum
      diamine oxides (DAOs) and d-xylose represented intestinal barrier function and
      absorption function, respectively, and correlated with the extent of damage (P <
      0.05 and P < 0.05, respectively). We successfully developed a dog model of acute
      radiation enteritis, thus obtaining a relatively objective evaluation of
      intestinal tract injury based on clinical performance and laboratory examination.
      The method of assessment of the degree of intestinal tract injury after abdominal
      irradiation could be beneficial in the development of novel and effective
      therapeutic strategies for acute radiation enteritis.

PMID- 24872438
TI  - The improvement of spatial memory deficits in APP/V717I transgenic mice by
      chronic anti-stroke herb treatment.
AB  - In China, herbal medicine has an extensive history for the treatment of
      cerebrovascular diseases. Clinical studies have shown that stroke patients are
      more likely to experience significant memory decline in comparison to their
      healthy counterparts. Cognition is improved in stroke patients treated with
      herbal medicine active components, Geniposide (GP) and Geniposide Rg1 (GRg1)
      (together, called TLJN). However, the effect of TLJN in Alzheimer disease remains
      unknown. Therefore, we investigated the behavioral effect of TLJN in male and
      female APP/V717I transgenic (Tg) mice. We conducted two different treatment
      strategies: (1) pretreatment strategy: medically treated at the age of 3 months
      which lasted for 3 months; (2) early treatment strategy: medically treated at the
      age of 6 months which lasted for 4 months. In open field test, locomotor activity
      and anxiety-like behavior were not affected after TLJN administration in Tg mice.
      In Morris Water Maze test, spatial learning processes in both genders were
      improved by TLJN treatments. Furthermore, retrieval processes were significantly
      improved in the pretreatment strategy for only male mice, which also showed a
      trend for improved retrieval processes with early treatment. In the inhibitory
      avoidance test, TLJN enhanced learning processes. In addition, gender differences
      were found in Tg mice exposed to TLJN treatments. In Tg male mice, significant
      efficacy was seen at high and middle doses, and in Tg female mice, a low dose was
      more effective.

PMID- 24872439
TI  - MicroRNAs in human lung cancer.
AB  - Lung cancer, which can be divided into two major clinical-pathological
      categories, small cell lung cancer and non-small cell lung cancer, is the leading
      cause of cancer-related death worldwide. MicroRNAs (miRNAs), small non-coding
      RNAs approximately 22 nucleotides in length, have been reported to be upregulated
      or downregulated in disease states and specific cell types. Recently, miRNAs have
      gained recognition as major regulators of human gene expression. MiRNAs can
      control highly complex signal transduction pathways and other biological pathways
      by targeting and controlling gene expression, accounting for their important role
      in lung cancer. Findings from recent studies on the roles of miRNAs in lung
      cancer are summarized in this review. Understanding miRNA functions in lung
      cancer will bring molecular-level insight leading to better prognosis, diagnosis,
      and therapeutic approaches. 

PMID- 24872441
TI  - Anticoagulant and antiplatelet therapy during ocular surgery.

PMID- 24872442
TI  - Exercise during pregnancy attenuates prenatal depression: a randomized controlled
      trial.
AB  - Recent studies have estimated the prevalence of depression during pregnancy to be
      between 10% and 30%, which is higher than that in the postpartum period.
      Pharmacological treatment during pregnancy is difficult because of the possible
      side effects of antidepressants on the mother and the fetus. The aim of this
      study was to examine whether a supervised exercise program (EP) reduces
      depressive symptoms in pregnant women. A randomized controlled trial was
      designed. One hundred eighty four healthy pregnant women from Fuenlabrada
      Hospital were included (31.37 +/- 3.62 years). Women from the exercise group (EG)
      participated in a supervised EP consisting of three, 55- to 60-min sessions per
      week throughout pregnancy. The main outcome measure was the patients' depression
      level assessed by means of the Center for Epidemiologic Studies Depression Scale
      (CES-D). A total of 167 pregnant women were analyzed; 90 were allocated to the EG
      and 77 to the control group (CG). Significant differences were found between
      groups at the end of the study in CES-D scores (EG: 7.67 +/- 6.30 vs. CG: 11.34
      +/- 9.74, p = .005) and in percentages of pregnant women depressed (EG: n =
      11/12.2% vs. CG: n = 19/24.7%, p = .04). Our results show that supervised
      physical exercise during pregnancy reduces the level of depression and its
      incidence in pregnant women. 

PMID- 24872440
TI  - Techniques and assays for the study of angiogenesis.
AB  - The importance of studying angiogenesis, the formation of new blood vessels from
      pre-existing vessels, is underscored by its involvement in both normal
      physiology, such as embryonic growth and wound healing, and pathologies, such as
      diabetes and cancer. Treatments targeting the molecular drive of angiogenesis
      have been developed, but many of the molecular mechanisms that mediate
      vascularization, as well as how these mechanisms can be targeted in therapy,
      remain poorly understood. The limited capacity to quantify angiogenesis properly
      curtails our molecular understanding and development of new drugs and therapies.
      Although there are a number of assays for angiogenesis, many of them strip away
      its important components and/or limit control of the variables that direct this
      highly cooperative and complex process. Here we review assays commonly used in
      endothelial cell biology and describe the progress toward development of a
      physiologically realistic platform that will enable a better understanding of the
      molecular and physical mechanisms that govern angiogenesis. 

PMID- 24872443
TI  - Notes from the field: the evaluation of Maine Nutrition and Physical Activity
      Self-Assessment for Child Care (NAPSACC) experience.
AB  - More than half of all children in the United States aged 3 to 6 years are
      enrolled in child care centers. Maine received funds from the U.S. Department of
      Health and Human Services' Communities Putting Prevention to Work to promote the
      adoption of Nutrition and Physical Activity Self-Assessment for Child Care
      (NAPSACC), an evidence-based program for the child care setting. We evaluated the
      rollout and adoption of NAP SACC in Maine using multiple methods. Our findings
      suggest that the NAP SACC program has been successfully adopted in Maine.
      Nutrition and physical activity policies and offerings have improved, especially
      with regard to purchasing healthier options in the child care setting. 

PMID- 24872445
TI  - Parsing out the embryonic origin of subplate cell-type diversity.

PMID- 24872446
TI  - Branching out of the intein active site in protein splicing.

PMID- 24872444
TI  - Loss of quaternary structure is associated with rapid sequence divergence in the
      OSBS family.
AB  - The rate of protein evolution is determined by a combination of selective
      pressure on protein function and biophysical constraints on protein folding and
      structure. Determining the relative contributions of these properties is an
      unsolved problem in molecular evolution with broad implications for protein
      engineering and function prediction. As a case study, we examined the structural
      divergence of the rapidly evolving o-succinylbenzoate synthase (OSBS) family,
      which catalyzes a step in menaquinone synthesis in diverse microorganisms and
      plants. On average, the OSBS family is much more divergent than other protein
      families from the same set of species, with the most divergent family members
      sharing <15% sequence identity. Comparing 11 representative structures revealed
      that loss of quaternary structure and large deletions or insertions are
      associated with the family's rapid evolution. Neither of these properties has
      been investigated in previous studies to identify factors that affect the rate of
      protein evolution. Intriguingly, one subfamily retained a multimeric quaternary
      structure and has small insertions and deletions compared with related enzymes
      that catalyze diverse reactions. Many proteins in this subfamily catalyze both
      OSBS and N-succinylamino acid racemization (NSAR). Retention of ancestral
      structural characteristics in the NSAR/OSBS subfamily suggests that the rate of
      protein evolution is not proportional to the capacity to evolve new protein
      functions. Instead, structural features that are conserved among proteins with
      diverse functions might contribute to the evolution of new functions. 

PMID- 24872447
TI  - Evaporative emissions from tailings ponds are not likely an important source of
      airborne PAHs in the Athabasca oil sands region.

PMID- 24872448
TI  - Codon 104 of p53 is not an adaptively selected site for extreme environments in
      mammals of the Tibet plateau.

PMID- 24872449
TI  - Functional magnetic resonance microscopy at single-cell resolution in Aplysia
      californica.
AB  - In this work, we show the feasibility of performing functional MRI studies with
      single-cell resolution. At ultrahigh magnetic field, manganese-enhanced magnetic
      resonance microscopy allows the identification of most motor neurons in the
      buccal network of Aplysia at low, nontoxic Mn(2+) concentrations. We establish
      that Mn(2+) accumulates intracellularly on injection into the living Aplysia and
      that its concentration increases when the animals are presented with a sensory
      stimulus. We also show that we can distinguish between neuronal activities
      elicited by different types of stimuli. This method opens up a new avenue into
      probing the functional organization and plasticity of neuronal networks involved
      in goal-directed behaviors with single-cell resolution. 

PMID- 24872452
TI  - Trawling exerts big impacts on small beasts.

PMID- 24872451
TI  - Real-time conformational changes in LacY.
AB  - Galactoside/H(+) symport across the cytoplasmic membrane of Escherichia coli is
      catalyzed by lactose permease (LacY), which uses an alternating access mechanism
      with opening and closing of deep cavities on the periplasmic and cytoplasmic
      sides. In this study, conformational changes in LacY initiated by galactoside
      binding were monitored in real time by Trp quenching/unquenching of bimane, a
      small fluorophore covalently attached to the protein. Rates of change in bimane
      fluorescence on either side of LacY were measured by stopped flow with LacY in
      detergent or in proteoliposomes and were compared with rates of galactoside
      binding. With LacY in proteoliposomes, the periplasmic cavity is tightly sealed
      and the substrate-binding rate is limited by the rate of opening of this cavity.
      Rates of opening, measured as unquenching of bimane fluorescence, are 20-30 s(
      1), independent of sugar concentration and essentially the same in detergent or
      in proteoliposomes. On the cytoplasmic side of LacY in proteoliposomes, slow
      bimane quenching (i.e., closing of the cavity) is observed at a rate that is also
      independent of sugar concentration and similar to the rate of sugar binding from
      the periplasmic side. Therefore, opening of the periplasmic cavity not only
      limits access of sugar to the binding site of LacY but also controls the rate of
      closing of the cytoplasmic cavity. 

PMID- 24872450
TI  - Regulation of photosystem I light harvesting by zeaxanthin.
AB  - In oxygenic photosynthetic eukaryotes, the hydroxylated carotenoid zeaxanthin is
      produced from preexisting violaxanthin upon exposure to excess light conditions.
      Zeaxanthin binding to components of the photosystem II (PSII) antenna system has
      been investigated thoroughly and shown to help in the dissipation of excess
      chlorophyll-excited states and scavenging of oxygen radicals. However, the
      functional consequences of the accumulation of the light-harvesting complex I
      (LHCI) proteins in the photosystem I (PSI) antenna have remained unclarified so
      far. In this work we investigated the effect of zeaxanthin binding on
      photoprotection of PSI-LHCI by comparing preparations isolated from wild-type
      Arabidopsis thaliana (i.e., with violaxanthin) and those isolated from the A.
      thaliana nonphotochemical quenching 2 mutant, in which violaxanthin is replaced
      by zeaxanthin. Time-resolved fluorescence measurements showed that zeaxanthin
      binding leads to a previously unrecognized quenching effect on PSI-LHCI
      fluorescence. The efficiency of energy transfer from the LHCI moiety of the
      complex to the PSI reaction center was down-regulated, and an enhanced PSI
      resistance to photoinhibition was observed both in vitro and in vivo. Thus,
      zeaxanthin was shown to be effective in inducing dissipative states in PSI,
      similar to its well-known effect on PSII. We propose that, upon acclimation to
      high light, PSI-LHCI changes its light-harvesting efficiency by a zeaxanthin
      dependent quenching of the absorbed excitation energy, whereas in PSII the
      stoichiometry of LHC antenna proteins per reaction center is reduced directly. 

PMID- 24872455
TI  - Evaluating the utility of dynamical downscaling in agricultural impacts
      projections.
AB  - Interest in estimating the potential socioeconomic costs of climate change has
      led to the increasing use of dynamical downscaling--nested modeling in which
      regional climate models (RCMs) are driven with general circulation model (GCM)
      output--to produce fine-spatial-scale climate projections for impacts
      assessments. We evaluate here whether this computationally intensive approach
      significantly alters projections of agricultural yield, one of the greatest
      concerns under climate change. Our results suggest that it does not. We simulate
      US maize yields under current and future CO2 concentrations with the widely used
      Decision Support System for Agrotechnology Transfer crop model, driven by a
      variety of climate inputs including two GCMs, each in turn downscaled by two
      RCMs. We find that no climate model output can reproduce yields driven by
      observed climate unless a bias correction is first applied. Once a bias
      correction is applied, GCM- and RCM-driven US maize yields are essentially
      indistinguishable in all scenarios (<10% discrepancy, equivalent to error from
      observations). Although RCMs correct some GCM biases related to fine-scale
      geographic features, errors in yield are dominated by broad-scale (100s of
      kilometers) GCM systematic errors that RCMs cannot compensate for. These results
      support previous suggestions that the benefits for impacts assessments of
      dynamically downscaling raw GCM output may not be sufficient to justify its
      computational demands. Progress on fidelity of yield projections may benefit more
      from continuing efforts to understand and minimize systematic error in underlying
      climate projections.

PMID- 24872453
TI  - Ribosomal protein-Mdm2-p53 pathway coordinates nutrient stress with lipid
      metabolism by regulating MCD and promoting fatty acid oxidation.
AB  - The tumor suppressor p53 has recently been shown to regulate energy metabolism
      through multiple mechanisms. However, the in vivo signaling pathways related to
      p53-mediated metabolic regulation remain largely uncharacterized. By using mice
      bearing a single amino acid substitution at cysteine residue 305 of mouse double
      minute 2 (Mdm2(C305F)), which renders Mdm2 deficient in binding ribosomal
      proteins (RPs) RPL11 and RPL5, we show that the RP-Mdm2-p53 signaling pathway is
      critical for sensing nutrient deprivation and maintaining liver lipid
      homeostasis. Although the Mdm2(C305F) mutation does not significantly affect
      growth and development in mice, this mutation promotes fat accumulation under
      normal feeding conditions and hepatosteatosis under acute fasting conditions. We
      show that nutrient deprivation inhibits rRNA biosynthesis, increases RP-Mdm2
      interaction, and induces p53-mediated transactivation of malonyl-CoA
      decarboxylase (MCD), which catalyzes the degradation of malonyl-CoA to acetyl
      CoA, thus modulating lipid partitioning. Fasted Mdm2(C305F) mice demonstrate
      attenuated MCD induction and enhanced malonyl-CoA accumulation in addition to
      decreased oxidative respiration and increased fatty acid accumulation in the
      liver. Thus, the RP-Mdm2-p53 pathway appears to function as an endogenous sensor
      responsible for stimulating fatty acid oxidation in response to nutrient
      depletion. 

PMID- 24872454
TI  - Use of transmission electron microscopy to identify nanocrystals of challenging
      protein targets.
AB  - The current practice for identifying crystal hits for X-ray crystallography
      relies on optical microscopy techniques that are limited to detecting crystals no
      smaller than 5 MUm. Because of these limitations, nanometer-sized protein
      crystals cannot be distinguished from common amorphous precipitates, and
      therefore go unnoticed during screening. These crystals would be ideal candidates
      for further optimization or for femtosecond X-ray protein nanocrystallography.
      The latter technique offers the possibility to solve high-resolution structures
      using submicron crystals. Transmission electron microscopy (TEM) was used to
      visualize nanocrystals (NCs) found in crystallization drops that would
      classically not be considered as "hits." We found that protein NCs were readily
      detected in all samples tested, including multiprotein complexes and membrane
      proteins. NC quality was evaluated by TEM visualization of lattices, and
      diffraction quality was validated by experiments in an X-ray free electron laser.

PMID- 24872457
TI  - Development and initial psychometric properties of the Barriers to Physician
      Compassion questionnaire.
AB  - OBJECTIVE: Physicians are expected to be compassionate. However, most compassion
      research focuses on compassion fatigue--an outcome variable--rather than
      examining the specific factors that may interfere with compassion in a
      physician's practice. This report describes the development and early
      psychometric data for a self-report questionnaire assessing barriers to
      compassion among physicians. METHODS: In 2011, a pilot sample of 75 physicians
      helped to generate an initial list of barriers to compassion. A final 34 item
      Barriers to Physician Compassion (BPC) questionnaire was administered to 372
      convenience-sampled physicians together with measures of demographics, practice
      related variables, stress, locus of control and trait compassion. RESULTS: The
      barriers to physician compassion were not one-dimensional. Principal component
      analysis revealed the presence of four distinct, face-valid and discriminable
      factors--physician burnout/overload, external distractions, difficult
      patient/family and complex clinical situation. All barrier components had
      adequate internal reliabilities (>0.70) and meaningful patterns of convergent and
      divergent validity. CONCLUSIONS: Remaining compassionate in medical practice is
      difficult. With the newly developed BPC questionnaire, specific barriers to
      compassion can be assessed. These barriers illuminate potential targets for
      future self- and practice management, interventions and compassion training among
      physicians.

PMID- 24872458
TI  - The benefits of encouraging patients to email their doctor: a review of
      individual practice.

PMID- 24872456
TI  - Understanding positional cues in salamander limb regeneration: implications for
      optimizing cell-based regenerative therapies.
AB  - Regenerative medicine has reached the point where we are performing clinical
      trials with stem-cell-derived cell populations in an effort to treat numerous
      human pathologies. However, many of these efforts have been challenged by the
      inability of the engrafted populations to properly integrate into the host
      environment to make a functional biological unit. It is apparent that we must
      understand the basic biology of tissue integration in order to apply these
      principles to the development of regenerative therapies in humans. Studying
      tissue integration in model organisms, where the process of integration between
      the newly regenerated tissues and the 'old' existing structures can be observed
      and manipulated, can provide valuable insights. Embryonic and adult cells have a
      memory of their original position, and this positional information can modify
      surrounding tissues and drive the formation of new structures. In this Review, we
      discuss the positional interactions that control the ability of grafted cells to
      integrate into existing tissues during the process of salamander limb
      regeneration, and discuss how these insights could explain the integration
      defects observed in current cell-based regenerative therapies. Additionally, we
      describe potential molecular tools that can be used to manipulate the positional
      information in grafted cell populations, and to promote the communication of
      positional cues in the host environment to facilitate the integration of
      engrafted cells. Lastly, we explain how studying positional information in
      current cell-based therapies and in regenerating limbs could provide key insights
      to improve the integration of cell-based regenerative therapies in the future.

PMID- 24872459
TI  - Improving outcomes with bivalirudin in primary percutaneous coronary
      intervention.

PMID- 24872461
TI  - Eocene fossil is earliest evidence of flower-visiting by birds.
AB  - Birds are important pollinators, but the evolutionary history of ornithophily
      (bird pollination) is poorly known. Here, we report a skeleton of the avian taxon
      Pumiliornis from the middle Eocene of Messel in Germany with preserved stomach
      contents containing numerous pollen grains of an eudicotyledonous angiosperm. The
      skeletal morphology of Pumiliornis is in agreement with this bird having been a,
      presumably nectarivorous, flower-visitor. It represents the earliest and first
      direct fossil evidence of flower-visiting by birds and indicates a minimum age of
      47 million years for the origin of bird-flower interactions. As Pumiliornis does
      not belong to any of the modern groups of flower-visiting birds, the origin of
      ornithophily in some angiosperm lineages may have predated that of their extant
      avian pollinators. 

PMID- 24872460
TI  - The oldest ionoscopiform from China sheds new light on the early evolution of
      halecomorph fishes.
AB  - The Halecomorphi are a major subdivision of the ray-finned fishes. Although
      living halecomorphs are represented solely by the freshwater bowfin, Amia calva,
      this clade has a rich fossil history, and the resolution of interrelationships
      among extinct members is central to the problem of understanding the origin of
      the Teleostei, the largest clade of extant vertebrates. The Ionoscopiformes are
      extinct marine halecomorphs that were inferred to have originated in the Late
      Jurassic of Europe, and subsequently dispersed to the Early Cretaceous of the New
      World. Here, we report the discovery of a new ionoscopiform, Robustichthys
      luopingensis gen. et sp. nov., based on eight well-preserved specimens from the
      Anisian (242-247 Ma), Middle Triassic marine deposits of Luoping, eastern Yunnan
      Province, China. The new species documents the oldest known ionoscopiform,
      extending the stratigraphic range of this group by approximately 90 Ma, and the
      geographical distribution of this group into the Middle Triassic of South China,
      a part of eastern Palaeotethys Ocean. These new data provide a minimum estimate
      for the split of Ionoscopiformes from its sister clade Amiiformes and shed new
      light on the origin of ionoscopiform fishes. 

PMID- 24872462
TI  - Higher aggression towards closer relatives by soldier larvae in a polyembryonic
      wasp.
AB  - In the polyembryonic wasp Copidosoma floridanum, females commonly lay one male
      and one female egg in a lepidopteran host. Both sexes proliferate clonally within
      the growing host larva. Distinct larval castes develop from each wasp egg, the
      majority being 'reproductives' plus some 'soldiers' which sacrifice reproduction
      and attack competitors. Maturing mixed sex broods are usually female biased, as
      expected when intra-brood mating is common. Pre-mating dispersal followed by
      outbreeding is expected to increase sexual conflict over brood sex ratios and
      result in greater soldier attack rates. Owing to sexually asymmetric relatedness,
      intra-brood conflicts are expected to be resolved primarily via female soldier
      attack. We observed soldier behaviour in vitro to test whether lower intra-brood
      relatedness (siblings from either within-strain or between-strain crosses were
      presented) increased inter-sexual aggression by female as well as male soldiers.
      As found in prior studies, females were more aggressive than males but, contrary
      to expectations and previous empirical observations, soldiers of both sexes
      showed more aggression towards more closely related embryos. We speculate that
      lower intra-brood relatedness indicates maternal outbreeding and may suggest a
      rarity of mating opportunities for reproductives maturing from the current brood,
      which may enhance the value of opposite sex brood-mates, or that higher
      aggression towards relatives may be a side-effect of mechanisms to discriminate
      heterospecific competitors. 

PMID- 24872463
TI  - Control of self-motion in dynamic fluids: fish do it differently from bees.
AB  - To detect and avoid collisions, animals need to perceive and control the distance
      and the speed with which they are moving relative to obstacles. This is
      especially challenging for swimming and flying animals that must control movement
      in a dynamic fluid without reference from physical contact to the ground. Flying
      animals primarily rely on optic flow to control flight speed and distance to
      obstacles. Here, we investigate whether swimming animals use similar strategies
      for self-motion control to flying animals by directly comparing the trajectories
      of zebrafish (Danio rerio) and bumblebees (Bombus terrestris) moving through the
      same experimental tunnel. While moving through the tunnel, black and white
      patterns produced (i) strong horizontal optic flow cues on both walls, (ii) weak
      horizontal optic flow cues on both walls and (iii) strong optic flow cues on one
      wall and weak optic flow cues on the other. We find that the mean speed of
      zebrafish does not depend on the amount of optic flow perceived from the walls.
      We further show that zebrafish, unlike bumblebees, move closer to the wall that
      provides the strongest visual feedback. This unexpected preference for strong
      optic flow cues may reflect an adaptation for self-motion control in water or in
      environments where visibility is limited. 

PMID- 24872465
TI  - Policy Brief.

PMID- 24872464
TI  - Age-specific cost of first reproduction in female southern elephant seals.
AB  - When to commence breeding is a crucial life-history decision that may be the most
      important determinant of an individual's lifetime reproductive output and can
      have major consequences on population dynamics. The age at which individuals
      first reproduce is an important factor influencing the intensity of potential
      costs (e.g. reduced survival) involved in the first breeding event. However,
      quantifying age-related variation in the cost of first reproduction in wild
      animals remains challenging because of the difficulty in reliably recording the
      first breeding event. Here, using a multi-event capture-recapture model that
      accounts for both imperfect detection and uncertainty in the breeding status on
      an 18-year dataset involving 6637 individuals, we estimated age and state
      specific survival of female elephant seals (Mirounga leonina) in the declining
      Macquarie Island population. We detected a clear cost of first reproduction on
      survival. This cost was higher for both younger first-time breeders and older
      first-time breeders compared with females recruiting at age four, the overall
      mean age at first reproduction. Neither earlier primiparity nor delaying
      primiparity appear to confer any evolutionary advantage, rather the optimal
      strategy seems to be to start breeding at a single age, 4 years. 

PMID- 24872467
TI  - Obesity (Sometimes) Matters: The Importance of Context in the Relationship
      between Obesity and Life Satisfaction.
AB  - Previous research has established the negative influence of obesity on subjective
      well-being. In the present work, the authors use multilevel modeling and Behavior
      Risk Factor Surveillance System data (N = 1,319,340) to examine how this
      relationship is influenced by the prevalence of obesity in the contexts in which
      individuals are living and how such relationships vary by gender. The results
      suggest that some of the influence of obesity on life satisfaction is the result
      of relative comparison. Implications for both our understanding of the growing
      "obesity epidemic" and the study of subjective well-being are discussed.

PMID- 24872466
TI  - Family Influences on the Use of Mental Health Services among African Americans.
AB  - We examine how families influence mental health service (MHS) utilization among
      African Americans by drawing on the concept of family ambivalence, which
      encompasses both family support and stress, and by placing utilization within the
      context of family histories of psychiatric disorder and treatment. Data are from
      the 2001-2003 National Survey of American Life, a nationally representative
      sample of African American adults (n = 3,149), including a clinical need
      subsample (n = 605) of respondents with a disorder. Negative family interactions
      have indirect positive effects on use of any MHS through need for care, whereas
      family social support lacks any effect. Although poor self-rated mental health
      (SRMH) is associated with greater utilization of any and specialty MHS given
      family histories of no disorder or treated disorder, utilization is low given a
      family history of untreated disorder, irrespective of SRMH. Screening for family
      histories of psychiatric disorder in primary care is recommended.

PMID- 24872468
TI  - Incarceration and Post-release Health Behavior.
AB  - This study investigates the link between incarceration and health behavior among
      a sample of young adults from the National Longitudinal Study of Adolescent
      Health (N = 1,670). The association is analyzed using propensity score methods
      and a strategic comparison group: respondents who have been convicted of crimes,
      but not incarcerated. Findings suggest that former inmates consume more fast food
      and have a higher likelihood of smoking than do similarly situated peers. These
      associations operate partly through increased financial strife and decreased
      social standing. Given the role of health behavior in predicting future health
      outcomes, poor health behavior may be a salient force driving health and
      mortality risk among the formerly incarcerated population.

PMID- 24872469
TI  - A CD30(-) Transformed Mycosis Fungoides Case Responding Very Well to Systemic
      Bexarotene and Methotrexate.
AB  - The course of mycosis fungoides (MF) is indolent except when transformation to a
      large T-cell lymphoma occurs. The diagnosis of transformed MF relies on the
      presence of more than 25% of large cells on biopsy of an MF lesion. Treatment of
      transformed MF is a major challenge as these patients have poor outcome. Here, we
      report a 61-year-old man presenting with tumoral ulcer on the plantar area of the
      foot who was diagnosed cutaneous CD30(-) large cell transformed MF and treated
      with systemic methotraxate and bexarotene therapy.

PMID- 24872470
TI  - Wound Care Study and Translation Application: A Team's Work in China.
AB  - Trauma, tissue repair, and regeneration are frontier research areas in China and
      a team led by Professor Xiaobing Fu has become an important unit in this field in
      China. Over the past years, this team has played a key role in wound prevention,
      management, and some regulation making at the state level. The works on functions
      of growth factor and the action of these functions in regulating wound healing,
      stem cell biology, and its application for sweat gland regeneration, education,
      or training and prevention for chronic skin wounds are outstanding.

PMID- 24872471
TI  - Chronic Effect of Aspartame on Ionic Homeostasis and Monoamine Neurotransmitters
      in the Rat Brain.
AB  - Aspartame is one of the most widely used artificial sweeteners globally. Data
      concerning acute neurotoxicity of aspartame is controversial, and knowledge on
      its chronic effect is limited. In the current study, we investigated the chronic
      effects of aspartame on ionic homeostasis and regional monoamine neurotransmitter
      concentrations in the brain. Our results showed that aspartame at high dose
      caused a disturbance in ionic homeostasis and induced apoptosis in the brain. We
      also investigated the effects of aspartame on brain regional monoamine synthesis,
      and the results revealed that there was a significant decrease of dopamine in
      corpus striatum and cerebral cortex and of serotonin in corpus striatum.
      Moreover, aspartame treatment significantly alters the tyrosine hydroxylase
      activity and amino acids levels in the brain. Our data suggest that chronic use
      of aspartame may affect electrolyte homeostasis and monoamine neurotransmitter
      synthesis dose dependently, and this might have a possible effect on cognitive
      functions.

PMID- 24872473
TI  - Pericardial fat and postoperative atrial fibrillation after coronary artery
      bypass surgery.

PMID- 24872472
TI  - Assessment of cisplatin concentration and depth of penetration in human lung
      tissue after hyperthermic exposure.
AB  - OBJECTIVES: The effects of cisplatin on the lung parenchyma during hyperthermic
      intrathoracic chemotherapy perfusion have not been analysed in detail. The
      objective of this study was to evaluate both the concentration and depth of the
      penetration of cisplatin in human lung tissue after hyperthermic exposure under
      ex vivo conditions. METHODS: This experimental study was approved by the local
      ethics committee. Twelve patients underwent pulmonary wedge resections after
      elective thoracic lobectomies were performed (resected lobe), and the lung tissue
      (approximately 1-2 cm(3)) was incubated (in vitro) with cisplatin (0.05 mg/ml; 60
      min, 42 degrees C). Subsequent tissue beds (depth, 0.5 mm; median weight, 70-92
      mg) were prepared from the outside to the middle, and the amount of cisplatin per
      tissue weight was analysed using atomic absorption spectrometry. Afterwards, the
      penetration of cisplatin depth was calculated and related to the different
      concentrations per tissue. RESULTS: Cisplatin penetrated into the human lung
      tissue after ex vivo hyperthermic exposure. The median amount of platinum [nmol
      cisplatin/g lung tissue] decreased significantly (P <= 0.05) depending on the
      penetration depth: 32 nmol/g (1 mm), 20 nmol/g (2 mm) and 6.8 nmol/g (4 mm). The
      calculated median concentrations of cisplatin (ug/ml) were 2.4 ug/ml (1 mm), 1.4
      ug/ml (2 mm) and 0.5 ug/ml (4 mm), respectively. CONCLUSIONS: Under ex vivo
      hyperthermic conditions, cisplatin diffused into human lung tissue. The median
      penetration depth of the cisplatin was approximately 3-4 mm. The penetration of
      cisplatin into lung tissue may affect the local therapy of residual tumour cells
      on the lung surface using hyperthermic intrathoracic chemotherapy perfusion in
      patients with malignant pleural tumours.

PMID- 24872474
TI  - Congenital unilateral pulmonary atresia with coronary-to-pulmonary collateral
      artery originating from left circumflex coronary artery.
AB  - Major aortopulmonary collateral artery (MAPCA) is a rare vessel anomaly defect
      arising from the systemic arteries and supplying flow to the pulmonary capillary
      circulation, which frequently associates with cyanotic heart disease,
      particularly pulmonary atresia coexisting with ventricular septal defect and
      tetralogy of Fallot. The branches of MAPCA usually originate from the descending
      aorta, while a feeding vessel from a coronary artery directed to the pulmonary
      vasculature is a rare occurrence. Herein, we present the first case of right side
      pulmonary atresia with a variant of MAPCA originating from the left circumflex
      coronary artery to the pulmonary capillary circulation in a patient who presented
      with acute coronary syndrome. 

PMID- 24872476
TI  - Repair of tetralogy of Fallot-how much can we achieve with a single operation?

PMID- 24872475
TI  - Reply to Chhabra et al.

PMID- 24872477
TI  - Comparison between endobronchial ultrasound-guided transbronchial needle
      aspiration and 18F-fluorodeoxyglucose positron emission tomography in the
      diagnosis of postoperative nodal recurrence in patients with lung cancer.
AB  - OBJECTIVES: Endobronchial ultrasound-guided transbronchial needle aspiration
      (EBUS-TBNA) has a high diagnostic value for preoperative mediastinal staging in
      patients with lung cancer. In this study, the utility of EBUS-TBNA for the
      pathological diagnosis of postoperative lymph node recurrence was investigated
      and compared with that of (18)F-fluorodeoxyglucose positron emission tomography
      (FDG-PET). METHODS: Patients who received both EBUS-TBNA and FDG-PET for the
      diagnosis of postoperative lymph node recurrence were retrospectively
      investigated. They underwent routine chest computed tomography (CT) follow-up
      after thoracotomy, and when hilar or mediastinal lymph nodes showed enlargement
      on CT compared with the previous chest CT, they were referred for FDG-PET and
      EBUS-TBNA. We compared the diagnostic performance of these two modalities. In
      addition, pathological findings of the biopsied sample were evaluated precisely
      and compared with the results of FDG-PET. Positivity for hypermetabolism on FDG
      PET was defined as a standardized uptake value (SUV) greater than 2.5. RESULTS: A
      total of 40 patients were retrospectively reviewed. The sensitivity, specificity,
      positive predictive value, negative predictive value and diagnostic accuracy of
      EBUS-TBNA were 100% for each parameter, whereas those of FDG-PET were 95.8, 12.5,
      62.2, 66.7 and 62.5%, respectively. The SUV of true-positive nodes was
      significantly higher than that of false-positive nodes (P = 0.001). Twenty-two of
      24 patients who were confirmed for recurrence by EBUS-TBNA underwent anticancer
      treatment. The pathological diagnoses of 14 false-positive cases by FDG-PET were
      chronic inflammation in 12 and non-specific granuloma in 2. CONCLUSIONS: The
      diagnostic yield of EBUS-TBNA is higher than that of FDG-PET when postoperative
      lymph node recurrence is suspected.

PMID- 24872478
TI  - Uncommon side effect with a commonly used targeted agent: sunitinib-induced
      nephrotic syndrome in a patient with metastatic renal cell carcinoma.
AB  - The authors report the case of a 67-year-old woman with metastatic renal cell
      carcinoma (RCC) without prior nephrectomy, who had received long-term exposure
      (38 months) to the oral multi-targeted tyrosine kinase inhibitor (TKI),
      sunitinib. She had a sustained clinical and radiological response to her therapy,
      but had this therapy discontinued due to the rare development of nephrotic
      syndrome.

PMID- 24872479
TI  - Calyceal diverticulum: a benign imitator of serious pathology.
AB  - A 72-year-old man with lung cancer underwent positron emission tomography CT (PET
      CT) as a part of cancer staging. As an incidental finding, the PET-CT revealed a
      renal mass with metabolic and morphological characteristics of a malignant
      tumour. A diagnostic CT scan revealed a Bosniak III renal cyst, and malignancy
      could not be excluded. For correct Bosniak classification, a multiphasic contrast
      enhanced CT was performed and the renal mass was finally diagnosed as a calyceal
      diverticulum. This case report summarises how calyceal diverticula may mimic
      serious pathology, leading to diagnostic difficulties. 

PMID- 24872480
TI  - Jejunal intussusception: a rare cause of an acute abdomen in adults.
AB  - Abdominal pain secondary to intussusception is a common presentation in the
      paediatric population but rare in adults. Diagnosis is often difficult due to non
      specific signs and symptoms. Adult intussusception presents more insidiously with
      intermittent abdominal pain and signs and symptoms of an acute abdomen are rare.
      In children, the aetiological factor is usually idiopathic, whereas
      intussusception in adults is more commonly due to an underlying pathology giving
      rise to a lead point. Consequently the treatment of choice is different-while it
      is supportive in children, surgical management is typically indicated in adults.
      In addition, the causes of a lead point precipitating adult intussusception are
      different depending on whether they arise from the small or large bowel. This
      report presents a case of jejunal intussusception in a 30-year-old man with a
      characteristic CT scan who required exploratory laparotomy and small bowel
      resection. 

PMID- 24872481
TI  - Acrocyanosis in a young adult: a rare presentation of extra-adrenal
      pheochromocytoma.
AB  - Extra-adrenal pheochromocytomas (EAPs) are rare catecholamine-secreting tumours.
      The patient commonly present with headache, palpitation, anxiety, diaphoresis,
      raised blood pressure and heart rate which can be sustained or episodic and less
      commonly Raynaud's phenomenon. We present a case of an adult woman who presented
      with unilateral upper limb acrocyanosis and hypertension which was secondary to
      EAP and resolved completely after surgical removal of the tumour. 

PMID- 24872482
TI  - Specimen sign.

PMID- 24872484
TI  - Giant dumbbell-shaped schwannoma but not transforaminal: transdiaphragmatic.
AB  - A 31-year-old man reported a 3-month history of right upper abdominal pain and
      effort dyspnoea. The laboratory data demonstrated no abnormality. On abdominal
      ultrasound, a gross solid lesion with smooth borders was seen behind the liver.
      CT scan revealed a huge tumour, 23*17*15 cm in size, it was in the right
      posterior mediastinum and extended to the right retroperitoneum. In sagittal
      plane CT images, the lesion was like a dumbbell shape. CT-guided biopsy revealed
      a spindle cell tumour.

PMID- 24872485
TI  - Syringocysadenoma papilliferum of the vulva: a rarity in gynaecology.
AB  - A case of syringocystadenoma papilliferum of the vulva in a 36-year-old woman is
      reported .The patient presented with a single cystic lesion on the left labia
      minora of 8 years duration with a recent increase in size and redness around the
      lesion. Examination revealed a polypoid cystic lesion with no regional
      lymphadenopathy. An excision biopsy was performed under general anaesthesia and
      the specimen was subjected to histological examination. Histopathology revealed
      closely excised syringocystadenoma papilliferum. On follow-up, the patient was
      asymptomatic and the wound had healed well.

PMID- 24872483
TI  - A case of left main coronary artery embolus further embolising to the left
      anterior descending artery.
AB  - Coronary embolism is an uncommon cause of myocardial infarction. The usual source
      of a coronary embolus is an intracardiac thrombus or vegetation. Embolisation to
      the left main coronary artery is an extremely rare event and is usually fatal. We
      present a case of a 38-year-old woman with embolisation to the left main coronary
      artery which further embolised distally to the left anterior descending artery
      leading to a non-ST elevation myocardial infarction. The non-occlusive nature of
      the left main coronary artery embolus might have led to a favourable prognosis in
      our patient.

PMID- 24872486
TI  - Presentation of Mycobacterium abscessus infection following rhytidectomy to a UK
      plastic surgery unit.
AB  - We report the presentation of a patient to a UK plastic surgery unit with
      Mycobacterium abscessus infection following a facelift surgery in Southern India.
      Treatment was protracted requiring surgical debridement and 6 months of
      antibiotics including a 3-week hospital admission for intravenous antibiotic
      therapy. We describe the clinical presentation, diagnosis and treatment of this
      unusual microorganism with reference to more familiar pyogenic infections.

PMID- 24872487
TI  - Giant adrenal myelolipoma: when trauma and oncology collide.
AB  - Three patients presented some decades after severe traumatic injury with atypical
      bowel symptoms which were caused by a giant myelolipoma of the adrenal gland. The
      aetiology of this rare, benign and generally asymptomatic tumour is virtually
      unknown at present and several hypotheses have been devised. This report
      describes a possible association between high-energy trauma and the development
      of giant myelolipomas, further contributing to the hypothesis that severe
      systemic stress could be an aetiological factor in the development of an adrenal
      myelolipoma. 

PMID- 24872488
TI  - Prolonged, but transient, elevation of liver and biliary function tests in a
      healthy infant affected with breast milk jaundice.
AB  - Unconjugated hyperbilirubinaemia is a common finding in newborns. When it is
      exaggerated, it is usually investigated in order to exclude several diseases,
      such as newborn's haemolytic diseases, infections or hypothyroidism. Breast milk
      jaundice is a form of neonatal jaundice related to breast feeding and it is not
      usually associated with any clinical issue and/or other laboratory abnormalities.
      We describe a case of breast milk jaundice being associated, unexpectedly, to
      significant elevation of plasmatic liver and biliary enzymes. Despite the
      infant's good clinical condition and growth, several investigations were
      performed and these ruled out metabolic, infectious and autoimmune liver
      diseases. All liver function tests normalised by 6-7 months of life. We suggest
      that the finding of hypertransaminasaemia and hyper-gamma-glutamyl transpeptidase
      in a benign clinical context (similar to what we described) should be followed
      for 6-7 months before performing sophisticated and expensive diagnostic
      investigations which aim at excluding some unlikely and severe diseases in a
      completely asymptomatic infant.

PMID- 24872489
TI  - A 5-year-old boy with miliary and osteoarticular tuberculosis.
AB  - Osteoarticular involvement is one manifestation of extrapulmonary tuberculosis
      (TB). We present a 5-year-old Burmese boy with 10 months of right hip pain and
      decreased range of motion. The patient also had low-grade fever, cough and
      decreased appetite. The patient was undocumented and had recently moved from
      Myanmar. He was thin, in moderate distress with bilateral lung rhonchi, mild
      subcostal retractions, low back pain, right hip tenderness and painful and
      limited right range of motion. The patient's chest and pelvis radiographs showed
      a miliary pattern and right acetabulum osteolytic lesions, respectively. He was
      started on anti-TB medication and cefotaxime. Ofloxacin was added because of the
      concern of drug-resistant TB. The patient underwent a right hip debridement. His
      symptoms improved markedly, with improved mobility. TB is a challenging infection
      to diagnose, which can cause significant delays in management.

PMID- 24872490
TI  - Focal osteosclerosis of the skull in primary hyperparathyroidism.

PMID- 24872491
TI  - Recycling of jejunal effluent to enable enteral nutrition in short bowel
      syndrome.
AB  - A 41-year-old woman developed severe abdominal pain, distension and faeculent
      vomiting. CT of abdomen and pelvis revealed small bowel malrotation with a right
      paraduodenal hernia. At emergency laparotomy, a right paraduodenal hernia
      containing jejunum and ileum was identified. She had a viable duodenum with 50 cm
      of ischaemic proximal jejunum which was exteriorised as an end jejunostomy; 180
      cm of infarcted jejunum and ileum was resected. The proximal end of 150 cm of
      healthy ileum was exteriorised as a closed mucous fistula and 50 cm distally a
      feeding ileostomy was constructed. On day 5 postoperatively, jejunal effluent
      began to be recycled via her feeding ileostomy and she never required parenteral
      nutrition. Despite having only 50 cm of jejunum proximal to her stoma, recycling
      of effluent enabled her electrolytes to remain normal. She put on weight
      postoperatively and proceeded to closure of her stomas at 6 months, not requiring
      laparotomy.

PMID- 24872492
TI  - Ovarian carcinoid presenting with right heart failure.
AB  - A 69-year-old woman presented with a pelvic mass as well as a 6-month history of
      progressive bilateral peripheral oedema with more recent breathlessness and
      abdominal distension. She was found to have significant right heart failure (RHF)
      which was extensively investigated. No significant lung disease or pulmonary
      embolism was identified to explain the findings. Severe tricuspid incompetence
      was thus thought to be secondary to the systemic effects of a carcinoid tumour,
      confirmed to be ovarian in origin (on positron emission tomography/CT scan and
      histopathology). Prior to major pelvic surgery for removal of the ovarian mass,
      she underwent tricuspid and pulmonary valve replacement surgery due to the
      deteriorating right heart function. She had an uneventful recovery after both
      operations and continues to be followed up closely with serial ovarian and
      carcinoid tumour markers. 

PMID- 24872494
TI  - Lymphomatous orbital infiltration and vision loss in diffuse large B-cell
      lymphoma.

PMID- 24872493
TI  - Actinomyces infection causing acute right iliac fossa pain.
AB  - This is a case of a 75-year-old man being admitted to the on-call surgical
      department with acute abdominal pain. On arrival he was clinically dehydrated and
      shocked with localised pain over McBurney's point and examination findings were
      suggestive of appendiceal or other colonic pathology. Full blood testing revealed
      a white cell count of 38*10(9)/L and a C reactive protein (CRP) of 278 mg/L. A CT
      scan revealed a gallbladder empyema that extended into the right iliac fossa.
      This case highlights the potential for a hyperdistended gallbladder empyema to
      present as acute right iliac fossa pain with blood tests suggestive of
      complicated disease. Further analysis confirmed Actinomyces infection as the
      underlying aetiology prior to a laparoscopic subtotal cholecystectomy. This case
      serves to remind clinicians of this as a rare potential cause of atypical
      gallbladder pathology.

PMID- 24872495
TI  - Phenytoin-induced gingival enlargement.

PMID- 24872496
TI  - Diagnosis of coeliac disease after incidental finding of pneumatosis cystoides
      intestinalis.

PMID- 24872497
TI  - Mechanisms in endocrinology: vitamin D as a potential contributor in endocrine
      health and disease.
AB  - OBJECTIVE: It has been suggested that vitamin D may play a role in the
      pathogenesis of several endocrine diseases, such as hyperparathyroidism, type 1
      diabetes (T1DM), type 2 diabetes (T2DM), autoimmune thyroid diseases, Addison's
      disease and polycystic ovary syndrome (PCOS). In this review, we debate the role
      of vitamin D in the pathogenesis of endocrine diseases. METHODS: Narrative
      overview of the literature synthesizing the current evidence retrieved from
      searches of computerized databases, hand searches and authoritative texts.
      RESULTS: Evidence from basic science supports a role for vitamin D in many
      endocrine conditions. In humans, inverse relationships have been reported not
      only between blood 25-hydroxyvitamin D and parathyroid hormone concentrations but
      also with risk of T1DM, T2DM, and PCOS. There is less evidence for an association
      with Addison's disease or autoimmune thyroid disease. Vitamin D supplementation
      may have a role for prevention of T2DM, but the available evidence is not
      consistent. CONCLUSIONS: Although observational studies support a potential role
      of vitamin D in endocrine disease, high quality evidence from clinical trials
      does not exist to establish a place for vitamin D supplementation in optimizing
      endocrine health. Ongoing randomized controlled trials are expected to provide
      insights into the efficacy and safety of vitamin D in the management of endocrine
      disease.

PMID- 24872498
TI  - Three-dimensional traction forces of Schwann cells on compliant substrates.
AB  - The mechanical interaction between Schwann cells (SCs) and their microenvironment
      is crucial for the development, maintenance and repair of the peripheral nervous
      system. In this paper, we present a detailed investigation on the
      mechanosensitivity of SCs across a physiologically relevant substrate stiffness
      range. Contrary to many other cell types, we find that the SC spreading area and
      cytoskeletal actin architecture were relatively insensitive to substrate
      stiffness with pronounced stress fibre formation across all moduli tested (0.24
      4.80 kPa). Consistent with the presence of stress fibres, we found that SCs
      generated large surface tractions on stiff substrates and large, finite material
      deformations on soft substrates. When quantifying the three-dimensional
      characteristics of the SC traction profiles, we observed a significant
      contribution from the out-of-plane traction component, locally giving rise to
      rotational moments similar to those observed in mesenchymal embryonic
      fibroblasts. Taken together, these measurements provide the first set of
      quantitative biophysical metrics of how SCs interact with their physical
      microenvironment, which are anticipated to aid in the development of tissue
      engineering scaffolds designed to promote functional integration of SCs into post
      injury in vivo environments. 

PMID- 24872499
TI  - Patterns in melanocytic lesions: impact of the geometry on growth and transport
      inside the epidermis.
AB  - In glabrous skin, nevi and melanomas exhibit pigmented stripes during clinical
      dermoscopic examination. They find their origin in the basal layer geometry which
      periodically exhibits ridges, alternatively large (limiting ridges) and thin
      (intermediate ridges). However, nevus and melanoma lesions differ by the
      localization of the pigmented stripes along furrows or ridges of the epidermis
      surface. Here, we propose a biomechanical model of avascular tumour growth which
      takes into account this specific geometry in the epidermis where both kinds of
      lesions first appear. Simulations show a periodic distribution of tumour cells
      inside the lesion, with a global contour stretched out along the ridges. In order
      to be as close as possible to clinical observations, we also consider the melanin
      transport by the keratinocytes. Our simulations show that reasonable assumptions
      on melanocytic cell repartition in the ridges favour the limiting ridges of the
      basal compared with the intermediate ones in agreement with nevus observations
      but not really with melanomas. It raises the question of cell aggregation and
      repartition of melanocytic cells in acral melanomas and requires further
      biological studies of these cells in situ. 

PMID- 24872500
TI  - Modelling and analysis of bacterial tracks suggest an active reorientation
      mechanism in Rhodobacter sphaeroides.
AB  - Most free-swimming bacteria move in approximately straight lines, interspersed
      with random reorientation phases. A key open question concerns varying mechanisms
      by which reorientation occurs. We combine mathematical modelling with analysis of
      a large tracking dataset to study the poorly understood reorientation mechanism
      in the monoflagellate species Rhodobacter sphaeroides. The flagellum on this
      species rotates counterclockwise to propel the bacterium, periodically ceasing
      rotation to enable reorientation. When rotation restarts the cell body usually
      points in a new direction. It has been assumed that the new direction is simply
      the result of Brownian rotation. We consider three variants of a self-propelled
      particle model of bacterial motility. The first considers rotational diffusion
      only, corresponding to a non-chemotactic mutant strain. Two further models
      incorporate stochastic reorientations, describing 'run-and-tumble' motility. We
      derive expressions for key summary statistics and simulate each model using a
      stochastic computational algorithm. We also discuss the effect of cell geometry
      on rotational diffusion. Working with a previously published tracking dataset, we
      compare predictions of the models with data on individual stopping events in R.
      sphaeroides. This provides strong evidence that this species undergoes some form
      of active reorientation rather than simple reorientation by Brownian rotation. 

PMID- 24872501
TI  - Correlation of the dynamics of native human acetylcholinesterase and its
      inhibited huperzine A counterpart from sub-picoseconds to nanoseconds.
AB  - It is a long debated question whether catalytic activities of enzymes, which lie
      on the millisecond timescale, are possibly already reflected in variations in
      atomic thermal fluctuations on the pico- to nanosecond timescale. To shed light
      on this puzzle, the enzyme human acetylcholinesterase in its wild-type form and
      complexed with the inhibitor huperzine A were investigated by various neutron
      scattering techniques and molecular dynamics simulations. Previous results on
      elastic neutron scattering at various timescales and simulations suggest that
      dynamical processes are not affected on average by the presence of the ligand
      within the considered time ranges between 10 ps and 1 ns. In the work presented
      here, the focus was laid on quasi-elastic (QENS) and inelastic neutron scattering
      (INS). These techniques give access to different kinds of individual diffusive
      motions and to the density of states of collective motions at the sub-picoseconds
      timescale. Hence, they permit going beyond the first approach of looking at mean
      square displacements. For both samples, the autocorrelation function was well
      described by a stretched-exponential function indicating a linkage between the
      timescales of fast and slow functional relaxation dynamics. The findings of the
      QENS and INS investigation are discussed in relation to the results of our
      earlier elastic incoherent neutron scattering and molecular dynamics simulations.

PMID- 24872503
TI  - Network-based vaccination improves prospects for disease control in wild
      chimpanzees.
AB  - Many endangered wildlife populations are vulnerable to infectious diseases for
      which vaccines exist; yet, pragmatic considerations often preclude large-scale
      vaccination efforts. These barriers could be reduced by focusing on individuals
      with the highest contact rates. However, the question then becomes whether
      targeted vaccination is sufficient to prevent large outbreaks. To evaluate the
      efficacy of targeted wildlife vaccinations, we simulate pathogen transmission and
      control on monthly association networks informed by behavioural data from a wild
      chimpanzee community (Kanyawara N = 37, Kibale National Park, Uganda). Despite
      considerable variation across monthly networks, our simulations indicate that
      targeting the most connected individuals can prevent large outbreaks with up to
      35% fewer vaccines than random vaccination. Transmission heterogeneities might be
      attributed to biological differences among individuals (e.g. sex, age, dominance
      and family size). Thus, we also evaluate the effectiveness of a trait-based
      vaccination strategy, as trait data are often easier to collect than interaction
      data. Our simulations indicate that a trait-based strategy can prevent large
      outbreaks with up to 18% fewer vaccines than random vaccination, demonstrating
      that individual traits can serve as effective estimates of connectivity. Overall,
      these results suggest that fine-scale behavioural data can help optimize pathogen
      control efforts for endangered wildlife. 

PMID- 24872504
TI  - Successful treatment of ball-shaped very late thrombus after myocardial
      infarction.

PMID- 24872505
TI  - Looking into the future.
AB  - Eye tracking experiments show that neurons respond rapidly to eye movements,
      allowing our view of the world to remain stable. 

PMID- 24872506
TI  - Plant quality declines as CO2 levels rise.
AB  - There is concern that crop plants are becoming less nutritious as the levels of
      carbon dioxide in the atmosphere increase. 

PMID- 24872507
TI  - The conserved ubiquitin-like protein Hub1 plays a critical role in splicing in
      human cells.
AB  - Different from canonical ubiquitin-like proteins, Hub1 does not form covalent
      conjugates with substrates but binds proteins non-covalently. In Saccharomyces
      cerevisiae, Hub1 associates with spliceosomes and mediates alternative splicing
      of SRC1, without affecting pre-mRNA splicing generally. Human Hub1 is highly
      similar to its yeast homolog, but its cellular function remains largely
      unexplored. Here, we show that human Hub1 binds to the spliceosomal protein Snu66
      as in yeast; however, unlike its S. cerevisiae homolog, human Hub1 is essential
      for viability. Prolonged in vivo depletion of human Hub1 leads to various
      cellular defects, including splicing speckle abnormalities, partial nuclear
      retention of mRNAs, mitotic catastrophe, and consequently cell death by
      apoptosis. Early consequences of Hub1 depletion are severe splicing defects,
      however, only for specific splice sites leading to exon skipping and intron
      retention. Thus, the ubiquitin-like protein Hub1 is not a canonical spliceosomal
      factor needed generally for splicing, but rather a modulator of spliceosome
      performance and facilitator of alternative splicing. 

PMID- 24872508
TI  - Methoprene-tolerant 1 regulates gene transcription to maintain insect larval
      status.
AB  - Insect molting and metamorphosis are regulated by two hormones: 20
      hydroxyecdysone (20E) and juvenile hormone (JH). The hormone 20E regulates gene
      transcription via the nuclear receptor EcR to promote metamorphosis, whereas JH
      regulates gene transcription via its intracellular receptor methoprene-tolerant
      (Met) to prevent larval-pupal transition. However, the function and mechanism of
      Met in various insect developments are not well understood. We propose that Met1
      plays a key role in maintaining larval status not only by promoting JH-responsive
      gene transcription but also by repressing 20E-responsive gene transcription in
      the Lepidopteran insect Helicoverpa armigera. Met1 protein is increased during
      feeding stage and decreased during molting and metamorphic stages. Met1 is
      upregulated by JH III and a low concentration of 20E independently, but is
      downregulated by a high concentration of 20E. Knockdown of Met1 in larvae causes
      precocious pupation, decrease in JH pathway gene expression, and increase in 20E
      pathway gene expression. Met1 interacts with heat shock protein 90 and binds to
      JH response element to regulate Kruppel homolog 1 transcription in JH III
      induction. Met1 interacts with ultraspiracle protein 1 (USP1) to repress 20E
      transcription complex EcRB1/USP1 formation and binding to ecdysone response
      element. These data indicate that JH via Met1 regulates JH pathway gene
      expression and represses 20E pathway gene expression to maintain the larval
      status. 

PMID- 24872502
TI  - USNCTAM perspectives on mechanics in medicine.
AB  - Over decades, the theoretical and applied mechanics community has developed
      sophisticated approaches for analysing the behaviour of complex engineering
      systems. Most of these approaches have targeted systems in the transportation,
      materials, defence and energy industries. Applying and further developing
      engineering approaches for understanding, predicting and modulating the response
      of complicated biomedical processes not only holds great promise in meeting
      societal needs, but also poses serious challenges. This report, prepared for the
      US National Committee on Theoretical and Applied Mechanics, aims to identify the
      most pressing challenges in biological sciences and medicine that can be tackled
      within the broad field of mechanics. This echoes and complements a number of
      national and international initiatives aiming at fostering interdisciplinary
      biomedical research. This report also comments on cultural/educational
      challenges. Specifically, this report focuses on three major thrusts in which we
      believe mechanics has and will continue to have a substantial impact. (i)
      Rationally engineering injectable nano/microdevices for imaging and therapy of
      disease. Within this context, we discuss nanoparticle carrier design, vascular
      transport and adhesion, endocytosis and tumour growth in response to therapy, as
      well as uncertainty quantification techniques to better connect models and
      experiments. (ii) Design of biomedical devices, including point-of-care
      diagnostic systems, model organ and multi-organ microdevices, and pulsatile
      ventricular assistant devices. (iii) Mechanics of cellular processes, including
      mechanosensing and mechanotransduction, improved characterization of cellular
      constitutive behaviour, and microfluidic systems for single-cell studies. 

PMID- 24872510
TI  - Influence of stromal-epithelial interactions on androgen action.
AB  - Androgen receptor (AR) signaling is vital to the development and function of the
      prostate and is a key pathway in prostate cancer. AR is differentially expressed
      in the stroma and epithelium, with both paracrine and autocrine control
      throughout the prostate. Stromal-epithelial interactions within the prostate are
      commonly dependent on AR signaling and expression. Alterations in these pathways
      can promote tumorigenesis. AR is also expressed in normal and malignant mammary
      tissues. Emerging data indicate a role for AR in certain subtypes of breast
      cancer that has the potential to be exploited therapeutically. The aim of this
      review is to highlight the importance of these interactions in normal development
      and tumorigenesis, with a focus on the prostate and breast.

PMID- 24872509
TI  - Structural basis for Pan3 binding to Pan2 and its function in mRNA recruitment
      and deadenylation.
AB  - The conserved eukaryotic Pan2-Pan3 deadenylation complex shortens cytoplasmic
      mRNA 3' polyA tails to regulate mRNA stability. Although the exonuclease activity
      resides in Pan2, efficient deadenylation requires Pan3. The mechanistic role of
      Pan3 is unclear. Here, we show that Pan3 binds RNA directly both through its
      pseudokinase/C-terminal domain and via an N-terminal zinc finger that binds polyA
      RNA specifically. In contrast, isolated Pan2 is unable to bind RNA. Pan3 binds to
      the region of Pan2 that links its N-terminal WD40 domain to the C-terminal part
      that contains the exonuclease, with a 2:1 stoichiometry. The crystal structure of
      the Pan2 linker region bound to a Pan3 homodimer shows how the unusual structural
      asymmetry of the Pan3 dimer is used to form an extensive high-affinity
      interaction. This binding allows Pan3 to supply Pan2 with substrate polyA RNA,
      facilitating efficient mRNA deadenylation by the intact Pan2-Pan3 complex. 

PMID- 24872511
TI  - Androgen deprivation therapy complications.
AB  - Androgen deprivation therapy (ADT) is increasingly used to treat advanced
      prostate cancer and is also utilised as adjuvant or neo-adjuvant treatment for
      high-risk disease. The resulting suppression of endogenous testosterone
      production has deleterious effects on quality of life, including hot flushes,
      reduced mood and cognition and diminished sexual function. Cross-sectional and
      longitudinal studies show that ADT has adverse bone and cardio-metabolic effects.
      The rate of bone loss is accelerated, increasing the risk of osteoporosis and
      subsequent fracture. Fat mass is increased and lean mass reduced, and adverse
      effects on lipid levels and insulin resistance are observed, the latter
      increasing the risk of developing type 2 diabetes. ADT also appears to increase
      the risk of incident cardiovascular events, although whether it increases
      cardiovascular mortality is not certain from the observational evidence published
      to date. Until high-quality evidence is available to guide management, it is
      reasonable to consider men undergoing ADT to be at a higher risk of psychosexual
      dysfunction, osteoporotic fracture, diabetes and cardiovascular disease,
      especially when treated for extended periods of time and therefore subjected to
      profound and prolonged hypoandrogenism. Health professionals caring for men
      undergoing treatment for prostate cancer should be aware of the potential risks
      of ADT and ensure appropriate monitoring and clinical management.

PMID- 24872512
TI  - Cytokine production assays reveal discriminatory immune defects in adults with
      recurrent infections and noninfectious inflammation.
AB  - Cytokine production assays have been primarily used in research settings studying
      novel immunodeficiencies. We sought to determine the diagnostic value of cytokine
      production assays in patients with recurrent and/or severe infectious diseases
      (IDs) without known immunodeficiencies and unclassified noninfectious
      inflammatory disorders (NIIDs). We retrospectively examined cytokine production
      in whole-blood and peripheral blood mononuclear cell samples from 157 adult
      patients. A cytokine production rate of <5% of that of healthy controls was
      considered defective. While monocyte-derived cytokine (tumor necrosis factor
      alpha [TNF-alpha], interleukin-1beta [IL-1beta], and IL-6) production was rarely
      affected, 30% of all included patients had deficient production of interferon
      gamma (IFN-gamma), IL-17A, or IL-22. Twenty-five percent of the NIID patients
      displayed defective IFN-gamma production, whereas IL-17A production was generally
      unaffected. In the group of ID patients, defective IFN-gamma production was found
      in 19% and 14% of the patients with viral and bacterial infections, respectively,
      and in 38%, 24%, and 50% of patients with mycobacterial, mucocutaneous, and
      invasive fungal infections, respectively. Defective IL-17A and IL-22 production
      was mainly confined to ID patients with mucocutaneous fungal infections. In
      conclusion, cytokine production assays frequently detect defective Th1 responses
      in patients with mycobacterial or fungal infections, in contrast to patients with
      respiratory tract infections or isolated bacterial infections. Defective IL-17A
      and IL-22 production was primarily found in patients with fungal infections,
      while monocyte-derived cytokine production was unaffected. Thus, lymphocyte
      derived cytokine production assays are helpful in the diagnostic workup of
      patients with recurrent infections and suspected immunodeficiencies and have the
      potential to reveal immune defects that might guide adjunctive immunomodulatory
      therapy. 

PMID- 24872513
TI  - Successful control of winter pyrexias caused by equine herpesvirus type 1 in
      Japanese training centers by achieving high vaccination coverage.
AB  - Equine herpesvirus type 1 (EHV-1) is a major cause of winter pyrexia in
      racehorses in two training centers (Ritto and Miho) in Japan. Until the epizootic
      period of 2008-2009, a vaccination program using a killed EHV-1 vaccine targeted
      only susceptible 3-year-old horses with low antibody levels to EHV-1 antigens.
      However, because the protective effect was not satisfactory, in 2009-2010 the
      vaccination program was altered to target all 3-year-old horses. To evaluate the
      vaccine's efficacy, we investigated the number of horses with pyrexia due to EHV
      1 or equine herpesvirus type 4 (EHV-4) infection or both and examined the
      vaccination coverage in the 3-year-old population and in the whole population
      before and after changes in the program. The mean (+/- standard deviation [SD])
      estimated numbers of horses infected with EHV-1 or EHV-4 or both, among pyretic
      horses from 1999-2000 to 2008-2009 were 105 +/- 47 at Ritto and 66 +/- 44 at
      Miho. Although the estimated number of infected horses did not change greatly in
      the first period of the current program, it decreased from the second period,
      with means (+/-SD) of 21 +/- 12 at Ritto and 14 +/- 15 at Miho from 2010-2011 to
      2012-2013. Vaccination coverage in the 3-year-old population was 99.4% at Ritto
      and 99.8% at Miho in the first period, and similar values were maintained
      thereafter. Coverage in the whole population increased more gradually than that
      in the 3-year-old population. The results suggest that EHV-1 epizootics can be
      suppressed by maintaining high vaccination coverage, not only in the 3-year-old
      population but also in the whole population. 

PMID- 24872514
TI  - Adaptation and attenuation of duck Tembusu virus strain Du/CH/LSD/110128
      following serial passage in chicken embryos.
AB  - Duck Tembusu virus (DTMUV) is a newly emerging pathogenic flavivirus that has
      caused massive economic losses to the duck industry in China. In the current
      study, a virulent strain of DTMUV, designated Du/CH/LSD/110128, was isolated from
      the livers of diseased ducks and attenuated by serial passage in embryonated
      chicken eggs. The virus was partially attenuated after 50 and 70 passages and was
      fully attenuated after 90 passages, based on mortality and morbidity rates and
      viral loads in inoculated ducklings. Fourteen amino acid substitutions were
      observed in the capsid, prM, envelope, NS1, NS3, NS4A, NS4B, and NS5 proteins of
      the fully attenuated strain of Du/CH/LSD/110128, which might be responsible for
      the observed changes in replication and pathogenicity. A 72-nucleotide deletion
      was also observed in the 3' untranslated region of the virus after 30 passages.
      The fully attenuated virus retained the immunogenicity of the parental strain,
      providing effective protection to challenge with virulent Du/CH/LSD/110128, and
      may represent a suitable candidate as a vaccine strain against DTMUV infection in
      ducks. Our results also lay the foundation for future studies on the replication
      and pathogenic mechanisms of DTMUV. 

PMID- 24872515
TI  - Macrophage depletion prior to Neospora caninum infection results in severe
      neosporosis in mice.
AB  - We observed that murine macrophages showed greater activation and increased
      interleukin 6 (IL-6), IL-12p40, and interferon gamma (IFN-gamma) production
      during Neospora caninum infection. Many macrophages migrated to the site of
      infection. Furthermore, macrophage-depleted mice exhibited increased sensitivity
      to N. caninum infection. This study indicates that macrophages are required for
      achieving protective immunity against N. caninum. 

PMID- 24872516
TI  - IgM, IgG, and IgA antibody responses to influenza A(H1N1)pdm09 hemagglutinin in
      infected persons during the first wave of the 2009 pandemic in the United States.
AB  - The novel influenza A(H1N1)pdm09 virus caused an influenza pandemic in 2009. IgM,
      IgG, and IgA antibody responses to A(H1N1)pdm09 hemagglutinin (HA) following
      A(H1N1)pdm09 virus infection were analyzed to understand antibody isotype
      responses. Age-matched control sera collected from U.S. residents in 2007 and
      2008 were used to establish baseline levels of cross-reactive antibodies. IgM
      responses often used as indicators of primary virus infection were mainly
      detected in young patient groups (<=5 years and 6 to 15 years old), not in older
      age groups, despite the genetic and antigenic differences between the HA of
      A(H1N1)pdm09 virus and pre-2009 seasonal H1N1 viruses. IgG and IgA responses to
      A(H1N1)pdm09 HA were detected in all age groups of infected persons. In persons
      17 to 80 years old, paired acute- and convalescent-phase serum samples
      demonstrated >=4-fold increases in the IgG and IgA responses to A(H1N1)pdm09 HA
      in 80% and 67% of A(H1N1)pdm09 virus-infected persons, respectively. The IgG
      antibody response to A(H1N1)pdm09 HA was cross-reactive with HAs from H1, H3, H5,
      and H13 subtypes, suggesting that infections with subtypes other than
      A(H1N1)pdm09 might result in false positives by enzyme-linked immunosorbent assay
      (ELISA). Lower sensitivity compared to hemagglutination inhibition and
      microneutralization assays and the detection of cross-reactive antibodies against
      homologous and heterologous subtype are major drawbacks for the application of
      ELISA in influenza serologic studies. 

PMID- 24872517
TI  - Sensitive and specific enzyme-linked immunosorbent assay for detecting serum
      antibodies against Mycobacterium avium subsp. paratuberculosis in fallow deer.
AB  - The enzyme-linked immunosorbent assay (ELISA) is the diagnostic test most
      commonly used in efforts to control paratuberculosis in domestic ruminants.
      However, commercial ELISAs have not been validated for detecting antibodies
      against Mycobacterium avium subsp. paratuberculosis in wild animals. In this
      study, we compared the sensitivities and specificities of five ELISAs using
      individual serum samples collected from 41 fallow deer with or without
      histopathological lesions consistent with paratuberculosis. Two target antigenic
      preparations were selected, an ethanol-treated protoplasmic preparation obtained
      from a fallow deer M. avium subsp. paratuberculosis isolate (ELISAs A and B) and
      a paratuberculosis protoplasmic antigen (PPA3) (ELISAs C and D). Fallow deer
      antibodies bound to the immobilized antigens were detected by using a horseradish
      peroxidase (HRP)-conjugated anti-fallow deer IgG antibody (ELISAs A and C) or HRP
      conjugated protein G (ELISAs B and D). A commercially available assay, ELISA-E,
      which was designed to detect M. avium subsp. paratuberculosis antibodies in
      cattle, sheep, and goats, was also tested. Although ELISAs A, C, and E had the
      same sensitivity (72%), ELISAs A and C were more specific (100%) for detecting
      fallow deer with lesions consistent with paratuberculosis at necropsy than was
      the ELISA-E (87.5%). In addition, the ELISA-A was particularly sensitive for
      detecting fallow deer in the latent stages of infection (62.5%). The antibody
      responses detected with the ELISA-A correlated with both the severity of enteric
      lesions and the presence of acid-fast bacteria in gut tissue samples. In summary,
      our study shows that the ELISA-A can be a cost-effective diagnostic tool for
      preventing the spread of paratuberculosis among fallow deer populations. 

PMID- 24872519
TI  - Comparing sampling strategies to recruit migrants for an epidemiological study.
      Results from a German feasibility study.
AB  - BACKGROUND: In 2011, almost 20.0% of the population of Germany had a migration
      background. Studies on their health tend to have low participation rates. The aim
      of our study was to compare different sampling strategies and to test different
      approaches to recruit migrants for an epidemiological study. METHODS: Four
      recruitment centres of the German National Cohort recruited persons of Turkish
      origin and ethnic German immigrants from former Soviet Union countries. A
      register-based (random samples from residents' registration offices) and a
      community-orientated strategy were applied. Participants underwent a medical
      examination and self-completed a questionnaire. RESULTS: Used approaches: The
      community-orientated strategies comprised the acquisition of key persons from
      migrant networks to support the recruitment, invitation talks and distribution of
      study materials in migrant settings, etc. The identifying variables in the
      registry data were name, nationality or country of birth. All but one centres
      used bilingual study material and study staff. PARTICIPATION: When comparing the
      two strategies, the register-based participation rates ranged from 10.1 to 21.0%
      (n = 668 participants) and the community-oriented recruitment resulted in 722
      participants. CONCLUSION: Register-based recruitment should use a combination of
      name, nationality and country of birth in order not to be limited to identifying
      persons with a foreign nationality. However, according to the study staff, the
      community-oriented approach involving key persons of the same cultural background
      leads to a better acceptance by the participants. Also, it covers a more
      heterogeneous group. Yet, it is time-consuming and needs considerably more staff.
      Further research should establish the effectiveness of a combination of both
      strategies.

PMID- 24872518
TI  - Chemically modified peptides based on the membrane-proximal external region of
      the HIV-1 envelope induce high-titer, epitope-specific nonneutralizing antibodies
      in rabbits.
AB  - Broadly neutralizing monoclonal antibodies (bNAbs) 2F5 and 4E10 bind to the
      membrane proximal external region (MPER) of gp41 and also cross-react with
      phospholipids. In this study, we investigated if chemical modifications on the
      MPER adjacent to 2F5 and 4E10 epitopes using mimetics of inflammation-associated
      posttranslational modifications to induce 2F5- and 4E10-like bNAbs can break
      tolerance. We synthesized a series of chemically modified peptides spanning the
      MPER. The serine, threonine, and tyrosine residues in the peptides were modified
      with sulfate, phosphate, or nitrate moieties and presented in liposomes for
      rabbit immunizations. All immunizations resulted in high antisera titers directed
      toward both the modified and unmodified immunogens. Tyrosine modification was
      observed to significantly suppress antiepitope responses. Sera with strong anti
      gp140 titers were purified by affinity chromatography toward the MPER peptide and
      found to possess a higher affinity toward the MPER than did the bNAbs 2F5 and
      4E10. Modest neutralization was observed in the H9 neutralization assay, but
      neutralization was not observed in the TZM-bl cell or peripheral blood
      mononuclear cell (PBMC) neutralization assay platforms. Although neutralizing
      antibodies were not induced by this approach, we conclude that chemical
      modifications can increase the immune responses to poorly immunogenic antigens,
      suggesting that chemical modification in an appropriate immunization protocol
      should be explored further as an HIV-1 vaccine strategy. 

PMID- 24872521
TI  - Coordinated Recruitment of Cortical-Subcortical Circuits and Ascending Dopamine
      and Serotonin Neurons During Inhibitory Control of Cocaine Seeking in Rats.
AB  - People with cocaine addiction retain some degree of prefrontal cortex (PFC)
      inhibitory control of cocaine craving, a brain capacity that may underlie the
      efficacy of cognitive behavioral therapy for addiction. Similar findings were
      recently found in rats after extended access to and escalation of cocaine self
      administration. Rats' inhibitory control of cocaine seeking was flexible,
      sufficiently strong to suppress cocaine-primed reinstatement and depended, at
      least in part, on neuronal activity within the prelimbic (PL) PFC. Here, we used
      a large-scale and high-resolution Fos mapping approach to identify, beyond the PL
      PFC, how top-down and/or bottom-up PFC-subcortical circuits are recruited during
      inhibition of cocaine seeking. Overall, we found that effective inhibitory
      control of cocaine seeking is associated with the coordinated recruitment of
      different top-down cortical-striatal circuits originating from different PFC
      territories, and of different bottom-up dopamine (DA) and serotonin (5-HT)
      midbrain subsystems that normally modulate activity in these circuits. This
      integrated brain response suggests that rats concomitantly engage and experience
      intricate cognitive and affective processes when they have to inhibit intense
      cocaine seeking. Thus, even after extended drug use, rats can be successfully
      trained to engage whole-brain inhibitory control mechanisms to suppress cocaine
      seeking. 

PMID- 24872520
TI  - Motivated Memories: Effects of Reward and Recollection in the Core Recollection
      Network and Beyond.
AB  - fMRI was employed to assess whether the neural correlates of accurate source
      memory are modulated by the reward value of recollected information. Study items
      comprised pictures of objects, each paired with a depiction of 1 of 2 coins. The
      reward value of the coins ($2.00 vs. $0.02) was disclosed after study. At test, a
      source memory procedure was employed in which subjects discriminated between
      studied and unstudied objects and, for objects judged studied, indicated the
      identity of the coin paired with the object at study. Correct judgments earned a
      reward corresponding to the value of the coin, whereas incorrect judgments were
      penalized. No regions were identified where the magnitude of recollection effects
      was modulated by reward. Exclusive effects of source accuracy were evident in the
      hippocampus. Different striatal sub-regions demonstrated exclusive recollection
      effects, exclusive reward effects, and overlap between the 2 effects. The left
      angular gyrus and medial prefrontal cortex were additively responsive to source
      accuracy and the reward. The findings suggest that reward value and recollection
      success are conjointly but independently represented in at least 2 cortical
      regions and that striatal retrieval success effects cannot be accounted for in
      terms of a single construct, such as goal satisfaction. 

PMID- 24872522
TI  - Comparison and analysis of organochlorine pesticides and hexabromobiphenyls in
      environmental samples by gas chromatography-electron capture detector and gas
      chromatography-mass spectrometry.
AB  - Two analytical methods, gas chromatography-electron capture detector (GC-ECD) and
      gas chromatography-negative chemical ionization-mass spectrometry (GC-NCI-MS),
      were evaluated and compared for the measurement of persistent organic pollutants,
      specifically for 26 organochlorine pesticides and two hexabromobiphenyls, in
      atmospheric particulate matter and soil samples. The hypothesis tested was that
      the coelution of non-target compounds may lead to false positives when analyzed
      by GC-ECD, and that the overestimation associated with these false positives can
      be eliminated using GC-NCI-MS. The study showed that both methods had
      satisfactory linearity and reproducibility for the target compounds. Although the
      sensitivities of GC-ECD for most of the compounds investigated were higher than
      those observed with the GC-NCI-MS method, the matrices interference was obvious
      with GC-ECD. There was indeed an apparently high false-positive rate or
      overestimate when GC-ECD was used for environmental samples, implying that the GC
      ECD method has been used with care and that GC-NCI-MS is generally superior for
      the analysis of trace amounts of these compounds in environmental samples. Based
      on these results, the sample extraction and cleanup procedures of the GC-NCI-MS
      method were optimized for achieving acceptable recoveries and less matrices
      interference. 

PMID- 24872523
TI  - Fingerprinting and simultaneous determination of alkaloids and limonins in
      Phellodendri amurensis cortex from different locations by high-performance liquid
      chromatography with diode array detection.
AB  - A sensitive high-performance liquid chromatography method coupled with diode
      array detection (HPLC-DAD) was developed for the quality control of Phellodendri
      amurensis cortex (PAC), the quality control included the simultaneous
      determination of seven major constituents, namely phellodendrine, magnoflorine,
      jatrorrhizine, palmatine, berberine, obaculactone and obacunone. The
      chromatographic separation was accomplished on a Diamonsil-C18 column (4.6 mm *
      200 mm, 5 MUm) with acetonitrile and 0.1% phosphoric acid (0.02 mol sodium
      dihydrogen phosphate per liter) by linear gradient elution. The established
      method was successfully validated by acceptable linearity, limits of detection
      and quantitation, precision, repeatability, stability and accuracy. The HPLC-DAD
      fingerprint chromatograph under 220 nm consisting of 21 peaks was constructed for
      the evaluation of the 11 batches of PAC. The HPLC fingerprints were analyzed by
      similarity analysis, hierarchical clustering analysis and principal component
      analysis. The results indicated that the combination of multicomponent
      determination method and chromatographic fingerprint analysis could be employed
      for the quantitative analysis and identification of PAC, as well as
      pharmaceutical products containing this herbal material. 

PMID- 24872524
TI  - Simultaneous estimation of glycosidic isoflavones in fermented and unfermented
      soybeans by TLC-densitometric method.
AB  - A simple, accurate and rapid high-performance thin-layer chromatographic (HPTLC)
      method for the simultaneous quantification of three glycosidic isoflavones
      (daidzin, genistin and glycitin) in soybean (Glycine max L.) has been established
      and validated. Chromatography was performed on aluminum foil-backed silica gel 60
      F254 HPTLC plates and found compact spots for daidzin, genistin and glycitin (Rf
      value of 0.39, 0.51 and 0.32, respectively) with mobile phase toluene : ethyl
      acetate : formic acid : acetic acid in the ratio of 1 : 8 : 1 : 0.5, v/v/v/v.
      Ultraviolet detection was performed densitometrically at the maximum absorbance
      wavelength, 260 nm. The method was validated for precision, recovery, robustness,
      specificity, limit of detection (LOD) and limit of quantification (LOQ), in
      accordance with the ICH guidelines. The LOD (2.9, 19.3 and 3.5 ug mL(-1)), LOQ
      (9.03, 58.6 and 10.7 ug mL(-1)), recovery (95.9-106.66, 86.97-106.56 and 98.54
      105.65%) and precision (<=2.12, <=0.722 and <=0.066) were satisfactory for
      glycosidic form of isoflavones daidzin, genistin and glycitin, respectively.
      Soybean variety Kh-09 bragg was found to have relatively higher amount of
      glycosidic isoflavones, namely daidzin, genistin and glycitin 278, 597.5 and
      109.4 ug g(-1), respectively, and after fermentation the glycosidic isoflavones
      concentration in soybean fermented with Bacillus subtilis strain were decreased
      significantly after 24 h of incubation; conversely, aglycone isoflavones were
      increased significantly. The method for quantification of isoflavones in
      unfermented and fermented soybeans, with good resolution has been developed. 

PMID- 24872525
TI  - Identification of multiple constituents in Chinese medicinal prescription
      Shensong Yangxin capsule by ultra-fast liquid chromatography combined with
      quadrupole time-of-flight mass spectrometry.
AB  - A practical method using ultra-fast liquid chromatography in tandem with
      quadrupole time-of-flight mass spectrometry combined with dynamic background
      subtraction technology was developed for the rapid separation and identification
      of the complicated constituents in the Shensong Yangxin capsule (SSYX). The
      chromatographic separation was performed on a C18 column (2.1 * 100 mm, 2.6 MUm)
      with a gradient elution program using methanol and 0.1% formic acid aqueous
      solution as the mobile phase at a flow rate of 0.4 mL min(-1). Accurate mass
      measurements of the molecular ions in the full scan and the characteristic
      fragment ions triggered by information-dependent acquisition provided reliable
      identification criteria. Thus, 99 compounds, including saponins, phenolic acids,
      tanshinones, lignans, terpenoids, alkaloids and flavonoids, were unambiguously or
      tentatively identified in 40 min by comparing their retention times and accurate
      mass measurements for each molecular ion and its subsequent fragment ions with
      those of authentic standards or literature data. Simultaneously, all the
      compounds were further assigned to the individual raw materials. In conclusion,
      these results will provide a basis for quality control and further study of SSYX,
      and the proposed technique based on high-resolution mass spectrometry would be
      expected to be adaptable to the analysis of complicated constituents in various
      complex matrices. 

PMID- 24872526
TI  - Invisible visual stimuli elicit increases in alpha-band power.
AB  - The cerebral cortex responds to stimuli of a wide range of intensities. Previous
      studies have demonstrated that undetectably weak somatosensory stimuli cause a
      functional deactivation or inhibition in somatosensory cortex. In the present
      study, we tested whether invisible visual stimuli lead to similar responses,
      indicated by an increase in EEG alpha-band power-an index of cortical
      excitability. We presented subliminal and supraliminal visual stimuli after
      estimating each participant's detection threshold. Stimuli consisted of
      peripherally presented small circular patches that differed in their contrast to
      a background consisting of a random white noise pattern. We demonstrate that
      subliminal and supraliminal stimuli each elicit specific neuronal response
      patterns. Supraliminal stimuli evoked an early, strongly phase-locked lower
      frequency response representing the evoked potential and induced a decrease in
      alpha-band power from 400 ms on. By contrast, subliminal visual stimuli induced
      an increase of non-phase-locked power around 300 ms that was maximal within the
      alpha-band. This response might be due to an inhibitory mechanism, which reduces
      spurious visual activation that is unlikely to result from external stimuli. 

PMID- 24872528
TI  - Cholinergic EPSCs and their potentiation by bradykinin in single paratracheal
      ganglion neurons attached with presynaptic boutons.
AB  - We have found that bradykinin (BK) potentiates the nicotine-induced currents in
      airway paratracheal/parabronchial ganglia (PTG) neurons. In this study, we
      investigated if BK affects the cholinergic synaptic transmission in rat PTG
      neurons attached with synaptic buttons. Excitatory postsynaptic currents (EPSCs)
      were recorded in acutely dissociated PTG neurons attached with presynaptic
      boutons. EPSC frequency was increased in the high-K(+) external solution without
      affecting their amplitude. Activation and deactivation kinetics also did not
      change in the high-K(+) solution. Cd(2+) inhibited the EPSC frequency at 10(-7) M
      and also amplitude at higher concentrations without changing the kinetics.
      Mecamylamine inhibited both the amplitude and frequency of EPSCs and reduced the
      activation and deactivation kinetics. 10(-8) M BK potentiated the EPSC amplitude
      to 1.37 +/- 0.19 times of preapplication control. In addition, its frequency was
      increased to 2.04 +/- 0.41 times. BK did not affect the activation and
      deactivation kinetics. The effects of BK were mimicked by [Hyp(3)]-BK, a B2 kinin
      receptor agonist, whereas HOE 140, a B2 kinin receptor antagonist, abolished the
      effects of BK. In conclusion, BK potentiates the cholinergic synaptic
      transmission via B2 kinin receptors in the PTG. Since predominant control of
      airway function is thought to be exerted by cholinergic nerves arising from the
      PTG, the present findings might underlie at least partly the inflammatory
      pathological conditions of the lower airway. 

PMID- 24872527
TI  - Acetylcholine functionally reorganizes neocortical microcircuits.
AB  - Sensory information is processed and transmitted through the synaptic structure
      of local cortical circuits, but it is unclear how modulation of this architecture
      influences the cortical representation of sensory stimuli. Acetylcholine (ACh)
      promotes attention and arousal and is thought to increase the signal-to-noise
      ratio of sensory input in primary sensory cortices. Using high-speed two-photon
      calcium imaging in a thalamocortical somatosensory slice preparation, we recorded
      action potential activity of up to 900 neurons simultaneously and compared local
      cortical circuit activations with and without bath presence of ACh. We found that
      ACh reduced weak pairwise relationships and excluded neurons that were already
      unreliable during circuit activity. Using action potential activity from the
      imaged population, we generated functional wiring diagrams based on the
      statistical dependencies of activity between neurons. ACh pruned weak functional
      connections from spontaneous circuit activations and yielded a more modular and
      hierarchical circuit structure, which biased activity to flow in a more
      feedforward fashion. Neurons that were active in response to thalamic input had
      reduced pairwise dependencies overall, but strong correlations were conserved.
      This coincided with a prolonged period during which neurons showed temporally
      precise responses to thalamic input. Our results demonstrate that ACh reorganizes
      functional circuit structure in a manner that may enhance the integration and
      discriminability of thalamic afferent input within local neocortical circuitry. 

PMID- 24872530
TI  - Explaining autism spectrum disorders: central coherence vs. predictive coding
      theories.
AB  - In this article, we review a recent paper by Stevenson et al. (J Neurosci 34: 691
      697, 2014). This paper illustrates the need to present different forms of stimuli
      in order to characterize the perceptual abilities of people with autism spectrum
      disorder (ASD). Furthermore, we will discuss their behavioral results and offer
      an opposing viewpoint to the suggested neuronal drivers of ASD. 

PMID- 24872529
TI  - Neural and genetic degeneracy underlies Caenorhabditis elegans feeding behavior.
AB  - Degenerate networks, in which structurally distinct elements can perform the same
      function or yield the same output, are ubiquitous in biology. Degeneracy
      contributes to the robustness and adaptability of networks in varied
      environmental and evolutionary contexts. However, how degenerate neural networks
      regulate behavior in vivo is poorly understood, especially at the genetic level.
      Here, we identify degenerate neural and genetic mechanisms that underlie
      excitation of the pharynx (feeding organ) in the nematode Caenorhabditis elegans
      using cell-specific optogenetic excitation and inhibition. We show that the
      pharyngeal neurons MC, M2, M4, and I1 form multiple direct and indirect
      excitatory pathways in a robust network for control of pharyngeal pumping. I1
      excites pumping via MC and M2 in a state-dependent manner. We identify nicotinic
      and muscarinic receptors through which the pharyngeal network regulates feeding
      rate. These results identify two different mechanisms by which degeneracy is
      manifest in a neural circuit in vivo. 

PMID- 24872532
TI  - The basis of orientation decoding in human primary visual cortex: fine- or coarse
      scale biases?
AB  - Orientation signals in human primary visual cortex (V1) can be reliably decoded
      from the multivariate pattern of activity as measured with functional magnetic
      resonance imaging (fMRI). The precise underlying source of these decoded signals
      (whether by orientation biases at a fine or coarse scale in cortex) remains a
      matter of some controversy, however. Freeman and colleagues (J Neurosci 33: 19695
      19703, 2013) recently showed that the accuracy of decoding of spiral patterns in
      V1 can be predicted by a voxel's preferred spatial position (the population
      receptive field) and its coarse orientation preference, suggesting that coarse
      scale biases are sufficient for orientation decoding. Whether they are also
      necessary for decoding remains an open question, and one with implications for
      the broader interpretation of multivariate decoding results in fMRI studies. 

PMID- 24872534
TI  - Developmental changes in biophysical properties of photoreceptors in the common
      water strider (Gerris lacustris): better performance at higher cost.
AB  - Although the dependence of invertebrate photoreceptor biophysical properties on
      visual ecology has already been investigated in some cases, developmental aspects
      have largely been ignored due to the general research emphasis on holometabolous
      insects. Here, using the patch-clamp method, we examined changes in biophysical
      properties and performance of photoreceptors in the common water strider Gerris
      lacustris during postembryonic development. We identified two types of peripheral
      photoreceptors, green and blue sensitive. Whole cell capacitance (a measure of
      cell size) of blue photoreceptors was significantly higher than the capacitance
      of green photoreceptors (69 +/- 20 vs. 43 +/- 12 pF, respectively). Most of the
      measured morphological and biophysical parameters changed with development.
      Photoreceptor capacitance increased progressively and was positively correlated
      with sensitivity to light, magnitudes and densities of light-induced (LIC) and
      delayed rectifier K(+) (IDR) currents, membrane corner frequency, and maximal
      information rate [Spearman rank correlation coefficients: 0.70 (sensitivity),
      0.79 (LIC magnitude), 0.79 (IDR magnitude), 0.48 (corner frequency), and 0.57
      (information rate)]. Transient K(+) current increased to a smaller extent, while
      its density decreased. We found no significant changes in the properties of
      single photon responses or levels of light-induced depolarization, the latter
      indicating a balanced channelome expansion associated with IDR expression.
      However, the dramatic ~7.6-fold increase in IDR from first instars to adults
      indicated a development-related rise in the metabolic cost of information. In
      conclusion, this study provides novel insights into functional photoreceptor
      adaptations with development and illustrates remarkable variability in patterns
      of postembryonic retinal development in hemimetabolous insects with dissimilar
      visual ecologies and behaviors. 

PMID- 24872531
TI  - Distinct subclassification of DRG neurons innervating the distal colon and glans
      penis/distal urethra based on the electrophysiological current signature.
AB  - Spinal sensory neurons innervating visceral and mucocutaneous tissues have unique
      microanatomic distribution, peripheral modality, and physiological,
      pharmacological, and biophysical characteristics compared with those neurons that
      innervate muscle and cutaneous tissues. In previous patch-clamp
      electrophysiological studies, we have demonstrated that small- and medium
      diameter dorsal root ganglion (DRG) neurons can be subclassified on the basis of
      their patterns of voltage-activated currents (VAC). These VAC-based subclasses
      were highly consistent in their action potential characteristics, responses to
      algesic compounds, immunocytochemical expression patterns, and responses to
      thermal stimuli. For this study, we examined the VAC of neurons retrogradely
      traced from the distal colon and the glans penis/distal urethra in the adult male
      rat. The afferent population from the distal colon contained at least two
      previously characterized cell types observed in somatic tissues (types 5 and 8),
      as well as four novel cell types (types 15, 16, 17, and 18). In the glans
      penis/distal urethra, two previously described cell types (types 6 and 8) and
      three novel cell types (types 7, 14, and 15) were identified. Other
      characteristics, including action potential profiles, responses to algesic
      compounds (acetylcholine, capsaicin, ATP, and pH 5.0 solution), and
      neurochemistry (expression of substance P, CGRP, neurofilament, TRPV1, TRPV2, and
      isolectin B4 binding) were consistent for each VAC-defined subgroup. With
      identification of distinct DRG cell types that innervate the distal colon and
      glans penis/distal urethra, future in vitro studies related to the
      gastrointestinal and urogenital sensory function in normal as well as
      abnormal/pathological conditions may be benefitted. 

PMID- 24872533
TI  - Axon diameters and conduction velocities in the macaque pyramidal tract.
AB  - Small axons far outnumber larger fibers in the corticospinal tract, but the
      function of these small axons remains poorly understood. This is because they are
      difficult to identify, and therefore their physiology remains obscure. To assess
      the extent of the mismatch between anatomic and physiological measures, we
      compared conduction time and velocity in a large number of macaque corticospinal
      neurons with the distribution of axon diameters at the level of the medullary
      pyramid, using both light and electron microscopy. At the electron microscopic
      level, a total of 4,172 axons were sampled from 2 adult male macaque monkeys. We
      confirmed that there were virtually no unmyelinated fibers in the pyramidal
      tract. About 14% of pyramidal tract axons had a diameter smaller than 0.50 MUm
      (including myelin sheath), most of these remaining undetected using light
      microscopy, and 52% were smaller than 1 MUm. In the electrophysiological study,
      we determined the distribution of antidromic latencies of pyramidal tract
      neurons, recorded in primary motor cortex, ventral premotor cortex, and
      supplementary motor area and identified by pyramidal tract stimulation (799
      pyramidal tract neurons, 7 adult awake macaques) or orthodromically from
      corticospinal axons recorded at the mid-cervical spinal level (192 axons, 5 adult
      anesthetized macaques). The distribution of antidromic and orthodromic latencies
      of corticospinal neurons was strongly biased toward those with large, fast
      conducting axons. Axons smaller than 3 MUm and with a conduction velocity below
      18 m/s were grossly underrepresented in our electrophysiological recordings, and
      those below 1 MUm (6 m/s) were probably not represented at all. The identity,
      location, and function of the majority of corticospinal neurons with small,
      slowly conducting axons remains unknown. 

PMID- 24872537
TI  - A preferred pattern of joint coordination during arm movements with redundant
      degrees of freedom.
AB  - Redundancy of degrees of freedom (DOFs) during natural human movements is a
      central problem of motor control research. This study tests a novel
      interpretation that during arm movements, the DOF redundancy is used to support a
      preferred, simplified joint control pattern that consists of rotating either the
      shoulder or elbow actively and the other (trailing) joint predominantly passively
      by interaction and gravitational torques. We previously revealed the preference
      for this control pattern during nonredundant horizontal arm movements. Here, we
      studied whether this preference persists during movements with redundant DOFs and
      the redundancy is used to enlarge the range of directions in which this control
      pattern can be utilized. A free-stroke drawing task was performed that involved
      production of series of horizontal center-out strokes in randomly selected
      directions. Two conditions were used, with the arm's joints unconstrained (U) and
      constrained (C) to the horizontal plane. In both conditions, directional
      preferences were revealed and the simplified control pattern was used in the
      preferred and not in nonpreferred directions. The directional preferences were
      weaker and the range of preferred directions was wider in the U condition, with
      higher percentage of strokes performed with the simplified control pattern. This
      advantage was related to the usage of additional DOFs. We discuss that the
      simplified pattern may represent a feedforward control strategy that reduces the
      challenge of joint coordination caused by signal-dependent noise during movement
      execution. The results suggest a possibility that the simplified pattern is used
      during the majority of natural, seemingly complex arm movements. 

PMID- 24872536
TI  - Effect of dual tasking on intentional vs. reactive balance control in people with
      hemiparetic stroke.
AB  - To examine the effect of a cognitive task on intentional vs. reactive balance
      control in people with hemiparetic stroke (PwHS). Community-dwelling PwHS (n =
      10) and healthy, age-similar controls performed two tests, which included the
      Limits of Stability Test (intentional control) and the Motor Control Test
      (reactive control), under single-task (ST) and dual-task (DT) conditions
      (addition of a cognitive task). Cognitive ability was measured on a word list
      generation task by recording the number of words enumerated in sitting (ST; for
      cognition) and during the balance tasks. The difference in response time between
      the ST and DT, defined as the "balance cost" was obtained [(ST - DT)/ST * 100]
      and compared between tests and across groups. The "cognitive cost" was similarly
      defined and compared. For both groups, the response time under DT condition was
      significantly greater for intentional than the reactive balance control task,
      leading to a higher balance cost for this task (P < 0.05). However, the cognitive
      cost was significantly greater for the intentional than the reactive balance
      control task for only the PwHS. DT significantly affected intentional than
      reactive balance control for PwHS. The significant decrease in both balance and
      cognitive performance under DT compared with ST conditions during intentional
      balance control suggests sharing of attentional resources between semantic memory
      and intentional balance control. Decreased performance on the cognitive task only
      during the reactive balance test indicates possible central nervous system's
      prioritization of reactive balance control over cognition. 

PMID- 24872535
TI  - A functional dissociation between language and multiple-demand systems revealed
      in patterns of BOLD signal fluctuations.
AB  - What is the relationship between language and other high-level cognitive
      functions? Neuroimaging studies have begun to illuminate this question, revealing
      that some brain regions are quite selectively engaged during language processing,
      whereas other "multiple-demand" (MD) regions are broadly engaged by diverse
      cognitive tasks. Nonetheless, the functional dissociation between the language
      and MD systems remains controversial. Here, we tackle this question with a
      synergistic combination of functional MRI methods: we first define candidate
      language-specific and MD regions in each subject individually (using functional
      localizers) and then measure blood oxygen level-dependent signal fluctuations in
      these regions during two naturalistic conditions ("rest" and story
      comprehension). In both conditions, signal fluctuations strongly correlate among
      language regions as well as among MD regions, but correlations across systems are
      weak or negative. Moreover, data-driven clustering analyses based on these inter
      region correlations consistently recover two clusters corresponding to the
      language and MD systems. Thus although each system forms an internally integrated
      whole, the two systems dissociate sharply from each other. This independent
      recruitment of the language and MD systems during cognitive processing is
      consistent with the hypothesis that these two systems support distinct cognitive
      functions. 

PMID- 24872538
TI  - Strychnine-sensitive glycine receptors on pyramidal neurons in layers II/III of
      the mouse prefrontal cortex are tonically activated.
AB  - Processing of signals within the cerebral cortex requires integration of synaptic
      inputs and a coordination between excitatory and inhibitory neurotransmission. In
      addition to the classic form of synaptic inhibition, another important mechanism
      that can regulate neuronal excitability is tonic inhibition via sustained
      activation of receptors by ambient levels of inhibitory neurotransmitter, usually
      GABA. The purpose of this study was to determine whether this occurs in layer
      II/III pyramidal neurons (PNs) in the prelimbic region of the mouse medial
      prefrontal cortex (mPFC). We found that these neurons respond to exogenous GABA
      and to the alpha4delta-containing GABAA receptor (GABA(A)R)-selective agonist
      gaboxadol, consistent with the presence of extrasynaptic GABA(A)R populations.
      Spontaneous and miniature synaptic currents were blocked by the GABA(A)R
      antagonist gabazine and had fast decay kinetics, consistent with typical synaptic
      GABA(A)Rs. Very few layer II/III neurons showed a baseline current shift in
      response to gabazine, but almost all showed a current shift (15-25 pA) in
      response to picrotoxin. In addition to being a noncompetitive antagonist at
      GABA(A)Rs, picrotoxin also blocks homomeric glycine receptors (GlyRs).
      Application of the GlyR antagonist strychnine caused a modest but consistent
      shift (~15 pA) in membrane current, without affecting spontaneous synaptic
      events, consistent with the tonic activation of GlyRs. Further investigation
      showed that these neurons respond in a concentration-dependent manner to glycine
      and taurine. Inhibition of glycine transporter 1 (GlyT1) with sarcosine resulted
      in an inward current and an increase of the strychnine-sensitive current. Our
      data demonstrate the existence of functional GlyRs in layer II/III of the mPFC
      and a role for these receptors in tonic inhibition that can have an important
      influence on mPFC excitability and signal processing.

PMID- 24872539
TI  - NaV1.5 sodium channel window currents contribute to spontaneous firing in
      olfactory sensory neurons.
AB  - Olfactory sensory neurons (OSNs) fire spontaneously as well as in response to
      odor; both forms of firing are physiologically important. We studied voltage
      gated Na(+) channels in OSNs to assess their role in spontaneous activity. Whole
      cell patch-clamp recordings from OSNs demonstrated both tetrodotoxin-sensitive
      and tetrodotoxin-resistant components of Na(+) current. RT-PCR showed mRNAs for
      five of the nine different Na(+) channel alpha-subunits in olfactory tissue; only
      one was tetrodotoxin resistant, the so-called cardiac subtype NaV1.5.
      Immunohistochemical analysis indicated that NaV1.5 is present in the apical knob
      of OSN dendrites but not in the axon. The NaV1.5 channels in OSNs exhibited two
      important features: 1) a half-inactivation potential near -100 mV, well below the
      resting potential, and 2) a window current centered near the resting potential.
      The negative half-inactivation potential renders most NaV1.5 channels in OSNs
      inactivated at the resting potential, while the window current indicates that the
      minor fraction of noninactivated NaV1.5 channels have a small probability of
      opening spontaneously at the resting potential. When the tetrodotoxin-sensitive
      Na(+) channels were blocked by nanomolar tetrodotoxin at the resting potential,
      spontaneous firing was suppressed as expected. Furthermore, selectively blocking
      NaV1.5 channels with Zn(2+) in the absence of tetrodotoxin also suppressed
      spontaneous firing, indicating that NaV1.5 channels are required for spontaneous
      activity despite resting inactivation. We propose that window currents produced
      by noninactivated NaV1.5 channels are one source of the generator potentials that
      trigger spontaneous firing, while the upstroke and propagation of action
      potentials in OSNs are borne by the tetrodotoxin-sensitive Na(+) channel
      subtypes. 

PMID- 24872540
TI  - Impact of lung cancer screening results on smoking cessation.
AB  - BACKGROUND: Lung cancer screening programs may provide opportunities to reduce
      smoking rates among participants. This study evaluates the impact of lung cancer
      screening results on smoking cessation. METHODS: Data from Lung Screening Study
      participants in the National Lung Screening Trial (NLST; 2002-2009) were used to
      prepare multivariable longitudinal regression models predicting annual smoking
      cessation in those who were current smokers at study entry (n = 15489, excluding
      those developing lung cancer in follow-up). The associations of lung cancer
      screening results on smoking cessation over the trial period were analyzed. All
      hypothesis testing used two sided P values. RESULTS: In adjusted analyses,
      smoking cessation was strongly associated with the amount of abnormality observed
      in the previous year's screening (P < .0001). Compared with those with a normal
      screen, individuals were less likely to be smokers if their previous year's
      screen had a major abnormality that was not suspicious for lung cancer (odds
      ratio [OR] = 0.811; 95% confidence interval [CI] = 0.722 to 0.912; P < .001), was
      suspicious for lung cancer but stable from previous screens (OR = 0.785; 95% CI =
      0.706 to 0.872; P < .001), or was suspicious for lung cancer and was new or
      changed from the previous screen (OR = 0.663; 95% CI = 0.607 to 0.724; P < .001).
      Differences in smoking prevalence were present up to 5 years after the last
      screen. CONCLUSIONS: Smoking cessation is statistically significantly associated
      with screen-detected abnormality. Integration of effective smoking cessation
      programs within screening programs should lead to further reduction in smoking
      related morbidity and mortality.

PMID- 24872541
TI  - Exposure to indoor tanning without burning and melanoma risk by sunburn history.
AB  - Indoor tanning is carcinogenic to humans. Individuals report that they tan
      indoors before planning to be in the sun to prevent sunburns, but whether skin
      cancer is subsequently reduced is unknown. Using a population-based case-control
      study, we calculated the association between melanoma and indoor tanning after
      excluding exposed participants reporting indoor tanning-related burns, stratified
      by their number of lifetime sunburns (0, 1-2, 3-5, >5). Confounding was addressed
      using propensity score analysis methods. All statistical tests were two-sided. We
      observed increased risk of melanoma across all sunburn categories for
      participants who had tanned indoors without burning compared with those who never
      tanned indoors, including those who reported zero lifetime sunburns (odds ratio =
      3.87; 95% confidence interval = 1.68 to 8.91; P = .002). These data provide
      evidence that indoor tanning is a risk factor for melanoma even among persons who
      reported never experiencing burns from indoor tanning or outdoor sun exposure. 

PMID- 24872542
TI  - Lung cancer screening and smoking cessation: a teachable moment?

PMID- 24872544
TI  - Digital mammography.

PMID- 24872545
TI  - The roles of sleep-wake states and brain rhythms in epileptic seizure onset.

PMID- 24872543
TI  - Benefits, harms, and costs for breast cancer screening after US implementation of
      digital mammography.
AB  - BACKGROUND: Compared with film, digital mammography has superior sensitivity but
      lower specificity for women aged 40 to 49 years and women with dense breasts.
      Digital has replaced film in virtually all US facilities, but overall population
      health and cost from use of this technology are unclear. METHODS: Using five
      independent models, we compared digital screening strategies starting at age 40
      or 50 years applied annually, biennially, or based on density with biennial film
      screening from ages 50 to 74 years and with no screening. Common data elements
      included cancer incidence and test performance, both modified by breast density.
      Lifetime outcomes included mortality, quality-adjusted life-years, and screening
      and treatment costs. RESULTS: For every 1000 women screened biennially from age
      50 to 74 years, switching to digital from film yielded a median within-model
      improvement of 2 life-years, 0.27 additional deaths averted, 220 additional false
      positive results, and $0.35 million more in costs. For an individual woman, this
      translates to a health gain of 0.73 days. Extending biennial digital screening to
      women ages 40 to 49 years was cost-effective, although results were sensitive to
      quality-of-life decrements related to screening and false positives. Targeting
      annual screening by density yielded similar outcomes to targeting by age. Annual
      screening approaches could increase costs to $5.26 million per 1000 women, in
      part because of higher numbers of screens and false positives, and were not
      efficient or cost-effective. CONCLUSIONS: The transition to digital breast cancer
      screening in the United States increased total costs for small added health
      benefits. The value of digital mammography screening among women aged 40 to 49
      years depends on women's preferences regarding false positives.

PMID- 24872546
TI  - Temporal signatures of taste quality driven by active sensing.
AB  - Animals actively acquire sensory information from the outside world, with rodents
      sniffing to smell and whisking to feel. Licking, a rapid motor sequence used for
      gustation, serves as the primary means of controlling stimulus access to taste
      receptors in the mouth. Using a novel taste-quality discrimination task in head
      restrained mice, we measured and compared reaction times to four basic taste
      qualities (salt, sour, sweet, and bitter) and found that certain taste qualities
      are perceived inherently faster than others, driven by the precise biomechanics
      of licking and functional organization of the peripheral gustatory system. The
      minimum time required for accurate perception was strongly dependent on taste
      quality, ranging from the sensory-motor limits of a single lick (salt, ~100 ms)
      to several sampling cycles (bitter, >500 ms). Further, disruption of sensory
      input from the anterior tongue significantly impaired the speed of perception of
      some taste qualities, with little effect on others. Overall, our results show
      that active sensing may play an important role in shaping the timing of taste
      quality representations and perception in the gustatory system. 

PMID- 24872547
TI  - Enriched expression of GluD1 in higher brain regions and its involvement in
      parallel fiber-interneuron synapse formation in the cerebellum.
AB  - Of the two members of the delta subfamily of ionotropic glutamate receptors,
      GluD2 is exclusively expressed at parallel fiber-Purkinje cell (PF-PC) synapses
      in the cerebellum and regulates their structural and functional connectivity.
      However, little is known to date regarding cellular and synaptic expression of
      GluD1 and its role in synaptic circuit formation. In the present study, we
      investigated this issue by producing specific and sensitive histochemical probes
      for GluD1 and analyzing cerebellar synaptic circuits in GluD1-knock-out mice.
      GluD1 was widely expressed in the adult mouse brain, with high levels in higher
      brain regions, including the cerebral cortex, striatum, limbic regions
      (hippocampus, nucleus accumbens, lateral septum, bed nucleus stria terminalis,
      lateral habenula, and central nucleus of the amygdala), and cerebellar cortex. In
      the cerebellar cortex, GluD1 mRNA was expressed at the highest level in molecular
      layer interneurons and its immunoreactivity was concentrated at PF synapses on
      interneuron somata. In GluD1-knock-out mice, the density of PF synapses on
      interneuron somata was significantly reduced and the size and number of
      interneurons were significantly diminished. Therefore, GluD1 is common to GluD2
      in expression at PF synapses, but distinct from GluD2 in neuronal expression in
      the cerebellar cortex; that is, GluD1 in interneurons and GluD2 in PCs.
      Furthermore, GluD1 regulates the connectivity of PF-interneuron synapses and
      promotes the differentiation and/or survival of molecular layer interneurons.
      These results suggest that GluD1 works in concert with GluD2 for the construction
      of cerebellar synaptic wiring through distinct neuronal and synaptic expressions
      and also their shared synapse-connecting function. 

PMID- 24872548
TI  - Cdk5-dependent Mst3 phosphorylation and activity regulate neuronal migration
      through RhoA inhibition.
AB  - The radial migration of newborn neurons is critical for the lamination of the
      cerebral cortex. Proper neuronal migration requires precise and rapid
      reorganization of the actin and microtubule cytoskeleton. However, the underlying
      signaling mechanisms controlling cytoskeletal reorganization are not well
      understood. Here, we show that Mst3, a serine/threonine kinase highly expressed
      in the developing mouse brain, is essential for radial neuronal migration and
      final neuronal positioning in the developing mouse neocortex. Mst3 silencing by
      in utero electroporation perturbed the multipolar-to-bipolar transition of
      migrating neurons and significantly retards radial migration. Although the kinase
      activity of Mst3 is essential for its functions in neuronal morphogenesis and
      migration, it is regulated via its phosphorylation at Ser79 by a serine/threonine
      kinase, cyclin-dependent kinase 5 (Cdk5). Our results show that Mst3 regulates
      neuronal migration through modulating the activity of RhoA, a Rho-GTPase critical
      for actin cytoskeletal reorganization. Mst3 phosphorylates RhoA at Ser26, thereby
      negatively regulating the GTPase activity of RhoA. Importantly, RhoA knockdown
      successfully rescues neuronal migration defect in Mst3-knockdown cortices. Our
      findings collectively suggest that Cdk5-Mst3 signaling regulates neuronal
      migration via RhoA-dependent actin dynamics. 

PMID- 24872549
TI  - Role of nucleus accumbens shell neuronal ensembles in context-induced
      reinstatement of cocaine-seeking.
AB  - Environmental contexts previously associated with drug use provoke relapse to
      drug use in humans and reinstatement of drug seeking in animal models of drug
      relapse. We examined whether context-induced reinstatement of cocaine seeking is
      mediated by activation of context-selected nucleus accumbens neurons. We trained
      rats to self-administer cocaine in Context A and extinguished their lever
      pressing in a distinct Context B. On test day, reexposure to the cocaine
      associated Context A reinstated cocaine seeking and increased expression of the
      neural activity marker Fos in 3.3% of accumbens shell and 1.6% of accumbens core
      neurons. To assess a causal role for these activated neurons, we used the Daun02
      inactivation procedure to selectively inactivate these neurons. We trained c-fos
      lacZ transgenic rats to self-administer cocaine in Context A and extinguished
      their lever-pressing in Context B. On induction day, we exposed rats to either
      Context A or a novel Context C for 30 min and injected Daun02 or vehicle into
      accumbens shell or core 60 min later. On test day, 3 d after induction day, the
      ability of Context A to reinstate cocaine seeking and increase neuronal activity
      in accumbens shell was attenuated when Daun02 was previously injected after
      exposure to Context A. Daun02 injections after exposure to the novel Context C
      had no effect on context-induced reinstatement of cocaine seeking despite much
      greater numbers of Fos-expressing neurons induced by Context C. Daun02 injections
      in accumbens core had no effect. Our data suggest that context-induced
      reinstatement of cocaine seeking is mediated by activation of context-selected
      accumbens shell but not core neuronal ensembles. 

PMID- 24872551
TI  - A TIGAR-regulated metabolic pathway is critical for protection of brain ischemia.
AB  - TP53-induced glycolysis and apoptosis regulator (TIGAR) inhibits glycolysis and
      increases the flow of pentose phosphate pathway (PPP), which generates NADPH and
      pentose. We hypothesized that TIGAR plays a neuroprotective role in brain
      ischemia as neurons do not rely on glycolysis but are vulnerable to oxidative
      stress. We found that TIGAR was highly expressed in brain neurons and was rapidly
      upregulated in response to ischemia/reperfusion insult in a TP53-independent
      manner. Overexpression of TIGAR in normal mice with lentivirus reduced ischemic
      neuronal injury, whereas lentivirus-mediated TIGAR knockdown aggravated it. In
      cultured primary neurons, increasing TIGAR expression reduced oxygen and glucose
      deprivation (OGD)/reoxygenation-induced injury, whereas decreasing its expression
      worsened the injury. The glucose 6-phosphate dehydrogenase was upregulated in
      mouse and cellular models of stroke, and its upregulation was further enhanced by
      overexpression of TIGAR. Supplementation of NADPH also reduced
      ischemia/reperfusion brain injury and alleviated TIGAR knockdown-induced
      aggravation of ischemic injury. In animal and cellular stroke models,
      ischemia/reperfusion increased mitochondrial localization of TIGAR.
      OGD/reoxygenation-induced elevation of ROS, reduction of GSH, dysfunction of
      mitochondria, and activation of caspase-3 were rescued by overexpression of TIGAR
      or supplementation of NADPH, while knockdown of TIGAR aggravated these changes.
      Together, our results show that TIGAR protects ischemic brain injury via
      enhancing PPP flux and preserving mitochondria function, and thus may be a
      valuable therapeutic target for ischemic brain injury. 

PMID- 24872550
TI  - A critical role of lateral hypothalamus in context-induced relapse to alcohol
      seeking after punishment-imposed abstinence.
AB  - In human alcoholics, abstinence is often self-imposed, despite alcohol
      availability, because of the negative consequences of excessive use. During
      abstinence, relapse is often triggered by exposure to contexts associated with
      alcohol use. We recently developed a rat model that captures some features of
      this human condition: exposure to the alcohol self-administration environment
      (context A), after punishment-imposed suppression of alcohol self-administration
      in a different environment (context B), provoked renewal of alcohol seeking in
      alcohol-preferring P rats. The mechanisms underlying context-induced renewal of
      alcohol seeking after punishment-imposed abstinence are unknown. Here, we studied
      the role of the lateral hypothalamus (LH) and its forebrain projections in this
      effect. We first determined the effect of context-induced renewal of alcohol
      seeking on Fos (a neuronal activity marker) expression in LH. We next determined
      the effect of LH reversible inactivation by GABAA + GABAB receptor agonists
      (muscimol + baclofen) on this effect. Finally, we determined neuronal activation
      in brain areas projecting to LH during context-induced renewal tests by measuring
      double labeling of the retrograde tracer cholera toxin subunit B (CTb; injected
      in LH) with Fos. Context-induced renewal of alcohol seeking after punishment
      imposed abstinence was associated with increased Fos expression in LH.
      Additionally, renewal was blocked by muscimol + baclofen injections into LH.
      Finally, double-labeling analysis of CTb + Fos showed that context-induced
      renewal of alcohol seeking after punishment-imposed abstinence was associated
      with selective activation of accumbens shell neurons projecting to LH. The
      results demonstrate an important role of LH in renewal of alcohol seeking after
      punishment-imposed abstinence and suggest a role of accumbens shell projections
      to LH in this form of relapse. 

PMID- 24872552
TI  - Global neural pattern similarity as a common basis for categorization and
      recognition memory.
AB  - Familiarity, or memory strength, is a central construct in models of cognition.
      In previous categorization and long-term memory research, correlations have been
      found between psychological measures of memory strength and activation in the
      medial temporal lobes (MTLs), which suggests a common neural locus for memory
      strength. However, activation alone is insufficient for determining whether the
      same mechanisms underlie neural function across domains. Guided by mathematical
      models of categorization and long-term memory, we develop a theory and a method
      to test whether memory strength arises from the global similarity among neural
      representations. In human subjects, we find significant correlations between
      global similarity among activation patterns in the MTLs and both subsequent
      memory confidence in a recognition memory task and model-based measures of memory
      strength in a category learning task. Our work bridges formal cognitive theories
      and neuroscientific models by illustrating that the same global similarity
      computations underlie processing in multiple cognitive domains. Moreover, by
      establishing a link between neural similarity and psychological memory strength,
      our findings suggest that there may be an isomorphism between psychological and
      neural representational spaces that can be exploited to test cognitive theories
      at both the neural and behavioral levels. 

PMID- 24872553
TI  - Synaptic modifications in the medial prefrontal cortex in susceptibility and
      resilience to stress.
AB  - When facing stress, most individuals are resilient whereas others are prone to
      developing mood disorders. The brain mechanisms underlying such divergent
      behavioral responses remain unclear. Here we used the learned helplessness
      procedure in mice to examine the role of the medial prefrontal cortex (mPFC), a
      brain region highly implicated in both clinical and animal models of depression,
      in adaptive and maladaptive behavioral responses to stress. We found that
      uncontrollable and inescapable stress induced behavioral state-dependent changes
      in the excitatory synapses onto a subset of mPFC neurons: those that were
      activated during behavioral responses as indicated by their expression of the
      activity reporter c-Fos. Whereas synaptic potentiation was linked to learned
      helplessness, a depression-like behavior, synaptic weakening, was associated with
      resilience to stress. Notably, enhancing the activity of mPFC neurons using a
      chemical-genetic method was sufficient to convert the resilient behavior into
      helplessness. Our results provide direct evidence that mPFC dysfunction is linked
      to maladaptive behavioral responses to stress, and suggest that enhanced
      excitatory synaptic drive onto mPFC neurons may underlie the previously reported
      hyperactivity of this brain region in depression. 

PMID- 24872554
TI  - Reinstatement of associative memories in early visual cortex is signaled by the
      hippocampus.
AB  - The cortical reinstatement hypothesis of memory retrieval posits that content
      specific cortical activity at encoding is reinstated at retrieval. Evidence for
      cortical reinstatement was found in higher-order sensory regions, reflecting
      reactivation of complex object-based information. However, it remains unclear
      whether the same detailed sensory, feature-based information perceived during
      encoding is subsequently reinstated in early sensory cortex and what the role of
      the hippocampus is in this process. In this study, we used a combination of
      visual psychophysics, functional neuroimaging, multivoxel pattern analysis, and a
      well controlled cued recall paradigm to address this issue. We found that the
      visual information human participants were retrieving could be predicted by the
      activation patterns in early visual cortex. Importantly, this reinstatement
      resembled the neural pattern elicited when participants viewed the visual stimuli
      passively, indicating shared representations between stimulus-driven activity and
      memory. Furthermore, hippocampal activity covaried with the strength of stimulus
      specific cortical reinstatement on a trial-by-trial level during cued recall.
      These findings provide evidence for reinstatement of unique associative memories
      in early visual cortex and suggest that the hippocampus modulates the mnemonic
      strength of this reinstatement. 

PMID- 24872555
TI  - The selective influence of rhythmic cortical versus cerebellar transcranial
      stimulation on human physiological tremor.
AB  - The influence of central neuronal oscillators on human physiological tremor is
      controversial. To address this, transcranial alternating current stimulation
      (TACS) was delivered at peak tremor frequency to 12 healthy volunteers in a 2 * 2
      crossover study. Two sites were stimulated [contralateral primary motor cortex
      (M1), vs ipsilateral cerebellum] while participants performed two types of tasks
      designed to probe the different manifestations of physiological tremor of the
      hand-kinetic and postural tremor. Tremor was measured by accelerometry. Cortical
      coherence with the accelerometry signal was also calculated in the absence of
      stimulation. The phase synchronization index, a measure of the phase entrainment
      of tremor, was calculated between stimulation and tremor waveforms. The amplitude
      modulation of tremor was similarly assessed. There was significant phase
      entrainment that was dependent both on tremor type and site of stimulation: M1
      stimulation gave rise to phase entrainment of postural, but not kinetic, tremor,
      whereas cerebellar stimulation increased entrainment in both cases. There was no
      effect on tremor amplitude. Tremor accelerometry was shown to be coherent with
      the cortical EEG recorded during postural, but not kinetic, tremor. TACS
      modulates physiological tremor, and its effects are dependent both on tremor type
      and stimulation site. Accordingly, central oscillators play a significant role in
      two of the major manifestations of tremor in health. 

PMID- 24872556
TI  - Motor inhibition affects the speed but not accuracy of aimed limb movements in an
      insect.
AB  - When reaching toward a target, human subjects use slower movements to achieve
      higher accuracy, and this can be accompanied by increased limb impedance
      (stiffness, viscosity) that stabilizes movements against motor noise and external
      perturbation. In arthropods, the activity of common inhibitory motor neurons
      influences limb impedance, so we hypothesized that this might provide a mechanism
      for speed and accuracy control of aimed movements in insects. We recorded
      simultaneously from excitatory leg motor neurons and from an identified common
      inhibitory motor neuron (CI1) in locusts that performed natural aimed scratching
      movements. We related limb movement kinematics to recorded motor activity and
      demonstrate that imposed alterations in the activity of CI1 influenced these
      kinematics. We manipulated the activity of CI1 by injecting depolarizing or
      hyperpolarizing current or killing the cell using laser photoablation. Naturally
      higher levels of inhibitory activity accompanied faster movements. Experimentally
      biasing the firing rate downward, or stopping firing completely, led to slower
      movements mediated by changes at several joints of the limb. Despite this, we
      found no effect on overall movement accuracy. We conclude that inhibitory
      modulation of joint stiffness has effects across most of the working range of the
      insect limb, with a pronounced effect on the overall velocity of natural
      movements independent of their accuracy. Passive joint forces that are greatest
      at extreme joint angles may enhance accuracy and are not affected by motor
      inhibition. 

PMID- 24872557
TI  - Distributed value representation in the medial prefrontal cortex during
      intertemporal choices.
AB  - The ability to resist current temptations in favor of long-term benefits is a
      critical human capacity. Despite the extensive studies on the neural mechanisms
      of intertemporal choices, how the subjective value of immediate and delayed
      rewards is represented and compared in the brain remains to be elucidated. The
      present fMRI study addressed this question by simultaneously and independently
      manipulating the magnitude of immediate and delayed rewards in an intertemporal
      decision task, combined with univariate analysis and multiple voxel pattern
      analysis. We found that activities in the posterior portion of the dorsal medial
      prefrontal cortex (DmPFC) were modulated by the value of immediate options,
      whereas activities in the adjacent anterior DmPFC were modulated by the
      subjective value of delayed options. Brain signal change in the ventral mPFC was
      positively correlated with the "relative value" (the absolute difference of
      subjective value between two intertemporal alternatives). In contrast, the dorsal
      anterior cingulate cortex activity was negatively correlated with the relative
      value. These results suggest that immediate and delayed rewards are separately
      represented in the dorsal mPFC and compared in the ventral mPFC to guide
      decisions. The functional dissociation of posterior and anterior DmPFC in
      representing immediate and delayed reward is consistent with the general
      structural and functional architecture of the prefrontal cortex and may provide a
      neural basis for human's unique capacity to delayed gratification. 

PMID- 24872559
TI  - Nonlinear spatial integration in the receptive field surround of retinal ganglion
      cells.
AB  - Throughout different sensory systems, individual neurons integrate incoming
      signals over their receptive fields. The characteristics of this signal
      integration are crucial determinants for the neurons' functions. For ganglion
      cells in the vertebrate retina, receptive fields are characterized by the well
      known center-surround structure and, although several studies have addressed
      spatial integration in the receptive field center, little is known about how
      visual signals are integrated in the surround. Therefore, we set out here to
      characterize signal integration and to identify relevant nonlinearities in the
      receptive field surround of ganglion cells in the isolated salamander retina by
      recording spiking activity with extracellular electrodes under visual stimulation
      of the center and surround. To quantify nonlinearities of spatial integration
      independently of subsequent nonlinearities of spike generation, we applied the
      technique of iso-response measurements as follows: using closed-loop experiments,
      we searched for different stimulus patterns in the surround that all reduced the
      center-evoked spiking activity by the same amount. The identified iso-response
      stimuli revealed strongly nonlinear spatial integration in the receptive field
      surrounds of all recorded cells. Furthermore, cell types that had been shown
      previously to have different nonlinearities in receptive field centers showed
      similar surround nonlinearities but differed systematically in the adaptive
      characteristics of the surround. Finally, we found that there is an optimal
      spatial scale of surround suppression; suppression was most effective when
      surround stimulation was organized into subregions of several hundred micrometers
      in diameter, indicating that the surround is composed of subunits that have
      strong center-surround organization themselves. 

PMID- 24872558
TI  - Cognitive control functions of anterior cingulate cortex in macaque monkeys
      performing a Wisconsin Card Sorting Test analog.
AB  - Monkeys were trained to select one of three targets by matching in color or
      matching in shape to a sample. Because the matching rule frequently changed and
      there were no cues for the currently relevant rule, monkeys had to maintain the
      relevant rule in working memory to select the correct target. We found that
      monkeys' error commission was not limited to the period after the rule change and
      occasionally occurred even after several consecutive correct trials, indicating
      that the task was cognitively demanding. In trials immediately after such error
      trials, monkeys' speed of selecting targets was slower. Additionally, in trials
      following consecutive correct trials, the monkeys' target selections for
      erroneous responses were slower than those for correct responses. We further
      found evidence for the involvement of the cortex in the anterior cingulate sulcus
      (ACCs) in these error-related behavioral modulations. First, ACCs cell activity
      differed between after-error and after-correct trials. In another group of ACCs
      cells, the activity differed depending on whether the monkeys were making a
      correct or erroneous decision in target selection. Second, bilateral ACCs lesions
      significantly abolished the response slowing both in after-error trials and in
      error trials. The error likelihood in after-error trials could be inferred by the
      error feedback in the previous trial, whereas the likelihood of erroneous
      responses after consecutive correct trials could be monitored only internally.
      These results suggest that ACCs represent both context-dependent and internally
      detected error likelihoods and promote modes of response selections in situations
      that involve these two types of error likelihood. 

PMID- 24872561
TI  - Associative Hebbian synaptic plasticity in primate visual cortex.
AB  - In primates, the functional connectivity of adult primary visual cortex is
      susceptible to be modified by sensory training during perceptual learning. It is
      widely held that this type of neural plasticity might involve mechanisms like
      long-term potentiation (LTP) and long-term depression (LTD). NMDAR-dependent
      forms of LTP and LTD are particularly attractive because in rodents they can be
      induced in a Hebbian manner by near coincidental presynaptic and postsynaptic
      firing, in a paradigm termed spike timing-dependent plasticity (STDP). These
      fundamental properties of LTP and LTD, Hebbian induction and NMDAR dependence,
      have not been examined in primate cortex. Here we demonstrate these properties in
      the primary visual cortex of the rhesus macaque (Macaca mulatta), and also show
      that, like in rodents, STDP is gated by neuromodulators. These findings indicate
      that the cellular principles governing cortical plasticity are conserved across
      mammalian species, further validating the use of rodents as a model system. 

PMID- 24872560
TI  - Enhancement of extinction learning attenuates ethanol-seeking behavior and alters
      plasticity in the prefrontal cortex.
AB  - Addiction is a chronic relapsing disorder in which relapse is often initiated by
      exposure to drug-related cues. The present study examined the effects of mGluR5
      activation on extinction of ethanol-cue-maintained responding, relapse-like
      behavior, and neuronal plasticity. Rats were trained to self-administer ethanol
      and then exposed to extinction training during which they were administered
      either vehicle or the mGluR5 positive allosteric modulator 3-cyano-N-(1,3
      diphenyl-1H-pyrazol-5-yl) or CDPPB. CDPPB treatment reduced active lever
      responding during extinction, decreased the total number of extinction sessions
      required to meet criteria, and attenuated cue-induced reinstatement of ethanol
      seeking. CDPPB facilitation of extinction was blocked by the local infusion of
      the mGluR5 antagonist 3-((2-methyl-4-thiazolyl)ethynyl) pyridine into the
      infralimbic (IfL) cortex, but had no effect when infused into the prelimbic (PrL)
      cortex. Analysis of dendritic spines revealed alterations in structural
      plasticity, whereas electrophysiological recordings demonstrated differential
      alterations in glutamatergic neurotransmission in the PrL and IfL cortex.
      Extinction was associated with increased amplitude of evoked synaptic PrL and IfL
      NMDA currents but reduced amplitude of PrL AMPA currents. Treatment with CDPPB
      prevented the extinction-induced enhancement of NMDA currents in PrL without
      affecting NMDA currents in the IfL. Whereas CDPPB treatment did not alter the
      amplitude of PrL or IfL AMPA currents, it did promote the expression of IfL
      calcium-permeable GluR2-lacking receptors in both abstinence- and extinction
      trained rats, but had no effect in ethanol-naive rats. These results confirm
      changes in the PrL and IfL cortex in glutamatergic neurotransmission during
      extinction learning and demonstrate that manipulation of mGluR5 facilitates
      extinction of ethanol cues in association with neuronal plasticity. 

PMID- 24872562
TI  - Value signals in the prefrontal cortex predict individual preferences across
      reward categories.
AB  - Humans can choose between fundamentally different options, such as watching a
      movie or going out for dinner. According to the utility concept, put forward by
      utilitarian philosophers and widely used in economics, this may be accomplished
      by mapping the value of different options onto a common scale, independent of
      specific option characteristics (Fehr and Rangel, 2011; Levy and Glimcher, 2012).
      If this is the case, value-related activity patterns in the brain should allow
      predictions of individual preferences across fundamentally different reward
      categories. We analyze fMRI data of the prefrontal cortex while subjects imagine
      the pleasure they would derive from items belonging to two distinct reward
      categories: engaging activities (like going out for drinks, daydreaming, or doing
      sports) and snack foods. Support vector machines trained on brain patterns
      related to one category reliably predict individual preferences of the other
      category and vice versa. Further, we predict preferences across participants.
      These findings demonstrate that prefrontal cortex value signals follow a common
      scale representation of value that is even comparable across individuals and
      could, in principle, be used to predict choice. 

PMID- 24872563
TI  - Induced alpha rhythms track the content and quality of visual working memory
      representations with high temporal precision.
AB  - Past work has suggested that neuronal oscillations coordinate the cellular
      assemblies that represent items in working memory (WM). In line with this
      hypothesis, we show that the spatial distribution of power in the alpha frequency
      band (8-12 Hz) can be used to decode the content and quality of the
      representations stored in visual WM. We acquired EEG data during an orientation
      WM task, and used a forward encoding model of orientation selectivity to
      reconstruct orientation-specific response profiles (termed channel tuning
      functions, or CTFs) that tracked the orientation of the memorandum during both
      encoding and delay periods of the trial. Critically, these EEG-based CTFs were
      robust predictors of both between- and within-subject differences in mnemonic
      precision, showing that EEG-based CTFs provide a sensitive measure of the quality
      of sensory population codes. Experiments 2 and 3 established that these EEG-based
      CTFs are contingent on the voluntary storage goals of the observer. When
      observers were given a postsample cue to store or drop the memorandum, the
      resulting CTF was sustained in the "store" condition and rapidly eliminated
      following the "drop" cue. When observers were instructed to store one of two
      simultaneously presented stimuli, only the stored item was represented in a
      sustained fashion throughout the delay period. These findings suggest that the
      oscillatory activity in the alpha frequency band plays a central role in the
      active storage of information in visual WM, and demonstrate a powerful approach
      for tracking the precision of on-line memories with high temporal resolution. 

PMID- 24872564
TI  - Multiple spatial and kinetic subpopulations of CaMKII in spines and dendrites as
      resolved by single-molecule tracking PALM.
AB  - Calcium/calmodulin-dependent protein kinase II (CaMKII) is essential for synaptic
      plasticity underlying memory formation. Some functions of CaMKII are mediated by
      interactions with synaptic proteins, and activity-triggered translocation of
      CaMKII to synapses has been heavily studied. However, CaMKII actions away from
      the postsynaptic density (PSD) remain poorly understood, in part because of the
      difficulty in discerning where CaMKII binds in live cells. We used photoactivated
      localization microscopy (PALM) in rat hippocampal neurons to track single
      molecules of CaMKIIalpha, mapping its spatial and kinetic heterogeneity at high
      resolution. We found that CaMKIIalpha exhibits at least three kinetic
      subpopulations, even within individual spines. Latrunculin application or
      coexpression of CaMKIIbeta carrying its actin-binding domain strongly modulated
      CaMKII diffusion, indicating that a major subpopulation is regulated by the actin
      cytoskeleton. CaMKII in spines was typically more slowly mobile than in
      dendrites, consistent with presence of a higher density of binding partners or
      obstacles. Importantly, NMDA receptor stimulation that triggered CaMKII
      activation prompted the immobilization and presumed binding of CaMKII in spines
      not only at PSDs but also at other points up to several hundred nanometers away,
      suggesting that activated kinase does not target only the PSD. Consistent with
      this, single endogenous activated CaMKII molecules detected via STORM
      immunocytochemistry were concentrated in spines both at the PSD and at points
      quite distant from the synapse. Together, these results indicate that CaMKII
      mobility within spines is determined by association with multiple interacting
      proteins, even outside the PSD, suggesting diverse mechanisms by which CaMKII may
      regulate synaptic transmission. 

PMID- 24872565
TI  - Kainate receptors mediate synaptic input to transient and sustained OFF visual
      pathways in primate retina.
AB  - Visual signals are segregated into parallel pathways at the first synapse in the
      retina between cones and bipolar cells. Within the OFF pathways of mammals, the
      selective expression of AMPA or kainate-type glutamate receptors in the dendrites
      of different OFF-bipolar cell types is thought to contribute to formation of
      distinct temporal channels. AMPA receptors, with rapid recovery from
      desensitization, are proposed to transmit high temporal frequency signals,
      whereas kainate receptors (KARs) are presumed to encode lower temporal
      frequencies. Here we studied the glutamate receptors expressed by OFF-bipolar
      cells in slice preparations of macaque monkey retina, where the low
      (midget/parvocellular) and high-frequency (parasol/magnocellular) temporal
      channels are well characterized. We found that all OFF-bipolar types receive
      input primarily through KARs and that KAR antagonists block light-evoked input to
      both OFF-midget and OFF-parasol ganglion cells. KAR subunits were differentially
      expressed in OFF-bipolar types; the diffuse bipolar (DB) cells, DB2 and DB3b,
      expressed GluK1 and showed transient responses to glutamate and the KAR agonist,
      ATPA. In contrast, flat midget bipolar, DB1, and DB3a cells lacked GluK1 and
      showed relatively sustained responses. Finally, we found that the KAR accessory
      protein, Neto1, is expressed at the base of cone pedicles but is not colocalized
      with the GluK1 subunit. In summary, the results indicate that transient signaling
      in the OFF pathway of macaques is not dependent on AMPA receptors and that
      heterogeneity of KARs and accessory proteins may contribute to the formation of
      parallel temporal channels. 

PMID- 24872567
TI  - Simultaneous recordings from the primary visual cortex and lateral geniculate
      nucleus reveal rhythmic interactions and a cortical source for gamma-band
      oscillations.
AB  - Oscillatory synchronization of neuronal activity has been proposed as a mechanism
      to modulate effective connectivity between interacting neuronal populations. In
      the visual system, oscillations in the gamma-frequency range (30-100 Hz) are
      thought to subserve corticocortical communication. To test whether a similar
      mechanism might influence subcortical-cortical communication, we recorded local
      field potential activity from retinotopically aligned regions in the lateral
      geniculate nucleus (LGN) and primary visual cortex (V1) of alert macaque monkeys
      viewing stimuli known to produce strong cortical gamma-band oscillations. As
      predicted, we found robust gamma-band power in V1. In contrast, visual
      stimulation did not evoke gamma-band activity in the LGN. Interestingly, an
      analysis of oscillatory phase synchronization of LGN and V1 activity identified
      synchronization in the alpha (8-14 Hz) and beta (15-30 Hz) frequency bands.
      Further analysis of directed connectivity revealed that alpha-band interactions
      mediated corticogeniculate feedback processing, whereas beta-band interactions
      mediated geniculocortical feedforward processing. These results demonstrate that
      although the LGN and V1 display functional interactions in the lower frequency
      bands, gamma-band activity in the alert monkey is largely an emergent property of
      cortex. 

PMID- 24872566
TI  - Overexpression of the astrocyte glutamate transporter GLT1 exacerbates phrenic
      motor neuron degeneration, diaphragm compromise, and forelimb motor dysfunction
      following cervical contusion spinal cord injury.
AB  - A major portion of spinal cord injury (SCI) cases affect midcervical levels, the
      location of the phrenic motor neuron (PhMN) pool that innervates the diaphragm.
      While initial trauma is uncontrollable, a valuable opportunity exists in the
      hours to days following SCI for preventing PhMN loss and consequent respiratory
      dysfunction that occurs during secondary degeneration. One of the primary causes
      of secondary injury is excitotoxic cell death due to dysregulation of
      extracellular glutamate homeostasis. GLT1, mainly expressed by astrocytes, is
      responsible for the vast majority of functional uptake of extracellular glutamate
      in the CNS, particularly in spinal cord. We found that, in bacterial artificial
      chromosome-GLT1-enhanced green fluorescent protein reporter mice following
      unilateral midcervical (C4) contusion SCI, numbers of GLT1-expressing astrocytes
      in ventral horn and total intraspinal GLT1 protein expression were reduced soon
      after injury and the decrease persisted for >=6 weeks. We used intraspinal
      delivery of adeno-associated virus type 8 (AAV8)-Gfa2 vector to rat cervical
      spinal cord ventral horn for targeting focal astrocyte GLT1 overexpression in
      areas of PhMN loss. Intraspinal delivery of AAV8-Gfa2-GLT1 resulted in
      transduction primarily of GFAP(+) astrocytes that persisted for >=6 weeks
      postinjury, as well as increased intraspinal GLT1 protein expression.
      Surprisingly, we found that astrocyte-targeted GLT1 overexpression increased
      lesion size, PhMN loss, phrenic nerve axonal degeneration, and diaphragm
      neuromuscular junction denervation, and resulted in reduced functional diaphragm
      innervation as assessed by phrenic nerve-diaphragm compound muscle action
      potential recordings. These results demonstrate that GLT1 overexpression via
      intraspinal AAV-Gfa2-GLT1 delivery exacerbates neuronal damage and increases
      respiratory impairment following cervical SCI. 

PMID- 24872568
TI  - The timing of dopamine- and noradrenaline-mediated transmission reflects
      underlying differences in the extent of spillover and pooling.
AB  - Metabotropic transmission typically occurs through the spillover activation of
      extrasynaptic receptors. This study examined the mechanisms underlying
      somatodendritic dopamine and noradrenaline transmission and found that the extent
      of spillover and pooling varied dramatically between these two transmitters. In
      the mouse ventral tegmental area, the time course of D2-receptor-mediated IPSCs
      (D2-IPSCs) was consistent between cells and was unaffected by altering
      stimulation intensity, probability of release, or the extent of diffusion.
      Blocking dopamine reuptake with cocaine extended the time course of D2-IPSCs and
      suggested that transporters strongly limited spillover. As a result, individual
      release sites contributed independently to the duration of D2-IPSCs. In contrast,
      increasing the release of noradrenaline in the rat locus ceruleus prolonged the
      duration of alpha2-receptor-mediated IPSCs even when reuptake was intact.
      Spillover and subsequent pooling of noradrenaline activated distal alpha2
      receptors, which prolonged the duration of alpha2-IPSCs when multiple release
      sites were activated synchronously. By using the rapid application of agonists
      onto large macropatches, we determined the concentration profile of agonists
      underlying the two IPSCs. Incorporating the results into a model simulating
      extracellular diffusion predicted that the functional range of noradrenaline
      diffusion was nearly fivefold greater in the locus ceruleus than dopamine in the
      midbrain. This study demonstrates that catecholamine synapses differentially
      regulate the extent of spillover and pooling to control the timing of local
      inhibition and suggests diversity in the roles of uptake and diffusion in
      governing metabotropic transmission. 

PMID- 24872569
TI  - Grb2-associated binder-1 is required for neuregulin-1-induced peripheral nerve
      myelination.
AB  - Grb2-associated binders (Gabs) are scaffolding proteins implicated in cell
      signaling via receptor tyrosine kinases including neuregulin-1(NRG1)-ErbB
      receptor signaling, which is essential for peripheral nerve myelination. Here, we
      show that the conditional removal of Gab1 from Schwann cells resulted in
      hypomyelination and abnormal development of Remak bundles. In contrast,
      hypomyelination was not observed in conventional Gab2 knock-out mice. Tyrosine
      phosphorylation of Gab1, but not Gab2, in sciatic nerves was upregulated during
      the myelination period and was found to be suppressed in NRG1-type III(+/-) mice,
      which display a hypomyelinated phenotype similar to that observed in Gab1 knock
      out mice. Gab1 knock-out and NRG1-type III(+/-) mice both exhibited reduced
      extracellular signal-regulated kinase activity in myelinating nerves. In
      addition, Krox20, a transcription factor that is critical for myelination, has
      been identified as a target of the NRG1-Gab1 pathway during the myelination
      process. Our findings suggest that Gab1 is an essential component of NRG1-type
      III signaling during peripheral nerve development. 

PMID- 24872570
TI  - Orbitofrontal dopamine depletion upregulates caudate dopamine and alters behavior
      via changes in reinforcement sensitivity.
AB  - Schizophrenia is associated with upregulation of dopamine (DA) release in the
      caudate nucleus. The caudate has dense connections with the orbitofrontal cortex
      (OFC) via the frontostriatal loops, and both areas exhibit pathophysiological
      change in schizophrenia. Despite evidence that abnormalities in dopaminergic
      neurotransmission and prefrontal cortex function co-occur in schizophrenia, the
      influence of OFC DA on caudate DA and reinforcement processing is poorly
      understood. To test the hypothesis that OFC dopaminergic dysfunction disrupts
      caudate dopamine function, we selectively depleted dopamine from the OFC of
      marmoset monkeys and measured striatal extracellular dopamine levels (using
      microdialysis) and dopamine D2/D3 receptor binding (using positron emission
      tomography), while modeling reinforcement-related behavior in a discrimination
      learning paradigm. OFC dopamine depletion caused an increase in tonic dopamine
      levels in the caudate nucleus and a corresponding reduction in D2/D3 receptor
      binding. Computational modeling of behavior showed that the lesion increased
      response exploration, reducing the tendency to persist with a recently chosen
      response side. This effect is akin to increased response switching previously
      seen in schizophrenia and was correlated with striatal but not OFC D2/D3 receptor
      binding. These results demonstrate that OFC dopamine depletion is sufficient to
      induce striatal hyperdopaminergia and changes in reinforcement learning relevant
      to schizophrenia. 

PMID- 24872571
TI  - False recall is reduced by damage to the ventromedial prefrontal cortex:
      implications for understanding the neural correlates of schematic memory.
AB  - Schematic memory, or contextual knowledge derived from experience (Bartlett,
      1932), benefits memory function by enhancing retention and speeding learning of
      related information (Bransford and Johnson, 1972; Tse et al., 2007). However,
      schematic memory can also promote memory errors, producing false memories. One
      demonstration is the "false memory effect" of the Deese-Roediger-McDermott (DRM)
      paradigm (Roediger and McDermott, 1995): studying words that fit a common schema
      (e.g., cold, blizzard, winter) often produces memory for a nonstudied word (e.g.,
      snow). We propose that frontal lobe regions that contribute to complex decision
      making processes by weighting various alternatives, such as ventromedial
      prefrontal cortex (vmPFC), may also contribute to memory processes by weighting
      the influence of schematic knowledge. We investigated the role of human vmPFC in
      false memory by combining a neuropsychological approach with the DRM task.
      Patients with vmPFC lesions (n = 7) and healthy comparison participants (n = 14)
      studied word lists that excluded a common associate (the critical item). Recall
      and recognition tests revealed expected high levels of false recall and
      recognition of critical items by healthy participants. In contrast, vmPFC
      patients showed consistently reduced false recall, with significantly fewer
      intrusions of critical items. False recognition was also marginally reduced among
      vmPFC patients. Our findings suggest that vmPFC increases the influence of
      schematically congruent memories, a contribution that may be related to the role
      of the vmPFC in decision making. These novel neuropsychological results highlight
      a role for the vmPFC as part of a memory network including the medial temporal
      lobes and hippocampus (Andrews-Hanna et al., 2010). 

PMID- 24872572
TI  - Neuromodulation of whisking related neural activity in superior colliculus.
AB  - The superior colliculus is part of a broader neural network that can decode
      whisker movements in air and on objects, which is a strategy used by behaving
      rats to sense the environment. The intermediate layers of the superior colliculus
      receive whisker-related excitatory afferents from the trigeminal complex and
      barrel cortex, inhibitory afferents from extrinsic and intrinsic sources, and
      neuromodulatory afferents from cholinergic and monoaminergic nuclei. However, it
      is not well known how these inputs regulate whisker-related activity in the
      superior colliculus. We found that barrel cortex afferents drive the superior
      colliculus during the middle portion of the rising phase of the whisker movement
      protraction elicited by artificial (fictive) whisking in anesthetized rats. In
      addition, both spontaneous and whisker-related neural activities in the superior
      colliculus are under strong inhibitory and neuromodulator control. Cholinergic
      stimulation activates the superior colliculus by increasing spontaneous firing
      and, in some cells, whisker-evoked responses. Monoaminergic stimulation has the
      opposite effects. The actions of neuromodulator and inhibitory afferents may be
      the basis of the different firing rates and sensory responsiveness observed in
      the superior colliculus of behaving animals during distinct behavioral states. 

PMID- 24872573
TI  - Violation of the craniocentricity principle for vestibularly evoked balance
      responses under conditions of anisotropic stability.
AB  - The balance response direction to electrically evoked vestibular perturbation is
      closely tied to head orientation. Such craniocentric response organization is
      expected of a simple error correction process. Here we ask whether this is
      maintained when the body is made more stable, but with the stability being
      greater in one direction than another. Since it is known that vestibularly evoked
      balance responses become smaller as body stability increases, the following two
      outcomes are possible: (1) response magnitude is attenuated, but with
      craniocentricity maintained; and (2) anisotropy of stability is considered such
      that components of the response are differentially attenuated, which would
      violate a craniocentric organizing principle. We tested these alternatives by
      measuring the direction of balance responses to electrical vestibular stimulation
      across a range of head orientations and stance widths in healthy humans. With
      feet together, the response was highly craniocentric. However, when stance width
      was increased so that the body was more stable in the frontal plane, response
      direction became biased toward the sagittal direction. This resulted in a
      nonlinear relationship between head orientation and response direction. While
      stance width changes the mechanical state of the body, the effect was also
      present when lateral light touch was used to produce anisotropy in stability,
      demonstrating that a significantly altered mechanical state was not crucial. We
      conclude that the balance system does not simply act according to the direction
      of vestibular input. Instead, it appears to assign greater relevance to
      components of vestibular input acting in the plane of lesser body stability than
      the plane of greater body stability, and acts accordingly. 

PMID- 24872575
TI  - Modeling inheritance of phase precession in the hippocampal formation.
AB  - Spatial information about the environment is encoded by the activity of place and
      grid cells in the hippocampal formation. As an animal traverses a cell's firing
      field, action potentials progressively shift to earlier phases of the theta
      oscillation (6-10 Hz). This "phase precession" is observed also in the prefrontal
      cortex and the ventral striatum, but mechanisms for its generation are unknown.
      However, once phase precession exists in one region, it might also propagate to
      downstream regions. Using a computational model, we analyze such inheritance of
      phase precession, for example, from the entorhinal cortex to CA1 and from CA3 to
      CA1. We find that distinctive subthreshold and suprathreshold features of the
      membrane potential of CA1 pyramidal cells (Harvey et al., 2009; Mizuseki et al.,
      2012; Royer et al., 2012) can be explained by inheritance and that excitatory
      input is essential. The model explains how inhibition modulates the slope and
      range of phase precession and provides two main testable predictions. First,
      theta-modulated inhibitory input to a CA1 pyramidal cell is not necessary for
      phase precession. Second, theta-modulated inhibitory input on its own generates
      membrane potential peaks that are in phase with peaks of the extracellular field.
      Furthermore, we suggest that the spatial distribution of field centers of a
      population of phase-precessing input cells determines, not only the place
      selectivity, but also the characteristics of phase precession of the targeted
      output cell. The inheritance model thus can explain why phase precession is
      observed throughout the hippocampal formation and other areas of the brain. 

PMID- 24872574
TI  - Achieving high-frequency optical control of synaptic transmission.
AB  - The optogenetic tool channelrhodopsin-2 (ChR2) is widely used to excite neurons
      to study neural circuits. Previous optogenetic studies of synapses suggest that
      light-evoked synaptic responses often exhibit artificial synaptic depression,
      which has been attributed to either the inability of ChR2 to reliably fire
      presynaptic axons or to ChR2 elevating the probability of release by depolarizing
      presynaptic boutons. Here, we compare light-evoked and electrically evoked
      synaptic responses for high-frequency stimulation at three synapses in the mouse
      brain. At synapses from Purkinje cells to deep cerebellar nuclei neurons (PC
      >DCN), light- and electrically evoked synaptic currents were remarkably similar
      for ChR2 expressed transgenically or with adeno-associated virus (AAV) expression
      vectors. For hippocampal CA3->CA1 synapses, AAV expression vectors of serotype 1,
      5, and 8 led to light-evoked synaptic currents that depressed much more than
      electrically evoked currents, even though ChR2 could fire axons reliably at up to
      50 Hz. The disparity between optical and electrical stimulation was eliminated
      when ChR2 was expressed transgenically or with AAV9. For cerebellar granule cell
      to stellate cell (grc->SC) synapses, AAV1 also led to artificial synaptic
      depression and AAV9 provided superior performance. Artificial synaptic depression
      also occurred when stimulating over presynaptic boutons, rather than axons, at
      CA3->CA1 synapses, but not at PC->DCN synapses. These findings indicate that ChR2
      expression methods and light stimulation techniques influence synaptic responses
      in a neuron-specific manner. They also identify pitfalls associated with using
      ChR2 to study synapses and suggest an approach that allows optogenetics to be
      applied in a manner that helps to avoid potential complications. 

PMID- 24872576
TI  - Different modes of GH administration influence gene expression in the male rat
      brain.
AB  - The endogenous secretion pattern in males of GH is episodic in rats and in
      humans, whereas GH administration is usually even. Different types of GH
      administration have different effects on body mass, longitudinal bone growth, and
      liver metabolism in rodents, whereas possible effects on brain plasticity have
      not been investigated. In this study, GH was administered as a continuous
      infusion or as two daily injections in hypophysectomized male rats. Thirteen
      transcripts previously known to respond to GH in the hippocampus and parietal
      cortex (cortex) were assessed by RT-PCR. To investigate the effects of type of GH
      administration on several transcripts with different variations, and categories
      of transcripts (neuron-, glia-, and GH-related), a mixed model analysis was
      applied. Accordingly, GH injections increased overall transcript abundance more
      than GH infusions (21% in the hippocampus, P<0.001 and 10% in the cortex,
      P=0.09). Specifically, GH infusions and injections robustly increased neuronal
      hemoglobin beta (Hbb) expression significantly (1.8- to 3.6-fold), and GH
      injections were more effective than GH infusions in increasing Hbb in the cortex
      (41%, P=0.02), whereas a 23% difference in the hippocampus was not significant.
      Also cortical connexin 43 was higher in the group with GH injections than in
      those with GH infusions (26%, P<0.007). Also, there were differences between GH
      injections and infusions in GH-related transcripts of the cortex (23%, P=0.04)
      and glia-related transcripts of the hippocampus (15%, P=0.02). Thus, with the
      exception of Hbb there is a moderate difference in responsiveness to different
      modes of GH administration. 

PMID- 24872577
TI  - Relative adrenal insufficiency in mice deficient in 5alpha-reductase 1.
AB  - Patients with critical illness or hepatic failure exhibit impaired cortisol
      responses to ACTH, a phenomenon known as 'relative adrenal insufficiency'. A
      putative mechanism is that elevated bile acids inhibit inactivation of cortisol
      in liver by 5alpha-reductases type 1 and type 2 and 5beta-reductase, resulting in
      compensatory downregulation of the hypothalamic-pituitary-adrenal axis and
      adrenocortical atrophy. To test the hypothesis that impaired glucocorticoid
      clearance can cause relative adrenal insufficiency, we investigated the
      consequences of 5alpha-reductase type 1 deficiency in mice. In adrenalectomised
      male mice with targeted disruption of 5alpha-reductase type 1, clearance of
      corticosterone was lower after acute or chronic (eightfold, P<0.05)
      administration, compared with WT control mice. In intact 5alpha-reductase
      deficient male mice, although resting plasma corticosterone levels were
      maintained, corticosterone responses were impaired after ACTH administration (26%
      lower, P<0.05), handling stress (2.5-fold lower, P<0.05) and restraint stress
      (43% lower, P<0.05) compared with WT mice. mRNA levels of Nr3c1 (glucocorticoid
      receptor), Crh and Avp in pituitary or hypothalamus were altered, consistent with
      enhanced negative feedback. These findings confirm that impaired peripheral
      clearance of glucocorticoids can cause 'relative adrenal insufficiency' in mice,
      an observation with important implications for patients with critical illness or
      hepatic failure, and for patients receiving 5alpha-reductase inhibitors for
      prostatic disease. 

PMID- 24872580
TI  - Defective viral genomes: critical danger signals of viral infections.
AB  - Viruses efficiently block the host antiviral response in order to replicate and
      spread before host intervention. The mechanism initiating antiviral immunity
      during stealth viral replication is unknown, but recent data demonstrate that
      defective viral genomes generated at peak virus replication are critical for this
      process in vivo. This article summarizes the supporting evidence and highlights
      gaps in our understanding of the mechanisms and impact of immunostimulatory
      defective viral genomes generated during natural infections. 

PMID- 24872579
TI  - Particle conformation regulates antibody access to a conserved GII.4 norovirus
      blockade epitope.
AB  - GII.4 noroviruses (NoVs) are the primary cause of epidemic viral acute
      gastroenteritis. One primary obstacle to successful NoV vaccination is the
      extensive degree of antigenic diversity among strains. The major capsid protein
      of GII.4 strains is evolving rapidly, resulting in the emergence of new strains
      with altered blockade epitopes. In addition to characterizing these evolving
      blockade epitopes, we have identified monoclonal antibodies (MAbs) that recognize
      a blockade epitope conserved across time-ordered GII.4 strains. Uniquely, the
      blockade potencies of MAbs that recognize the conserved GII.4 blockade epitope
      were temperature sensitive, suggesting that particle conformation may regulate
      functional access to conserved blockade non-surface-exposed epitopes. To map
      conformation-regulating motifs, we used bioinformatics tools to predict conserved
      motifs within the protruding domain of the capsid and designed mutant VLPs to
      test the impacts of substitutions in these motifs on antibody cross-GII.4
      blockade. Charge substitutions at residues 310, 316, 484, and 493 impacted the
      blockade potential of cross-GII.4 blockade MAbs with minimal impact on the
      blockade of MAbs targeting other, separately evolving blockade epitopes.
      Specifically, residue 310 modulated antibody blockade temperature sensitivity in
      the tested strains. These data suggest access to the conserved GII.4 blockade
      antibody epitope is regulated by particle conformation, temperature, and amino
      acid residues positioned outside the antibody binding site. The regulating motif
      is under limited selective pressure by the host immune response and may provide a
      robust target for broadly reactive NoV therapeutics and protective vaccines.
      IMPORTANCE: In this study, we explored the factors that govern norovirus (NoV)
      cross-strain antibody blockade. We found that access to the conserved GII.4
      blockade epitope is regulated by temperature and distal residues outside the
      antibody binding site. These data are most consistent with a model of NoV
      particle conformation plasticity that regulates antibody binding to a distally
      conserved blockade epitope. Further, antibody "locking" of the particle into an
      epitope-accessible conformation prevents ligand binding, providing a potential
      target for broadly effective drugs. These observations open lines of inquiry into
      the mechanisms of human NoV entry and uncoating, fundamental biological questions
      that are currently unanswerable for these noncultivatable pathogens.

PMID- 24872578
TI  - Virus particle release from glycosphingolipid-enriched microdomains is essential
      for dendritic cell-mediated capture and transfer of HIV-1 and henipavirus.
AB  - Human immunodeficiency virus type 1 (HIV-1) exploits dendritic cells (DCs) to
      promote its transmission to T cells. We recently reported that the capture of HIV
      1 by mature dendritic cells (MDCs) is mediated by an interaction between the
      glycosphingolipid (GSL) GM3 on virus particles and CD169/Siglec-1 on MDCs. Since
      HIV-1 preferentially buds from GSL-enriched lipid microdomains on the plasma
      membrane, we hypothesized that the virus assembly and budding site determines the
      ability of HIV-1 to interact with MDCs. In support of this hypothesis, mutations
      in the N-terminal basic domain (29/31KE) or deletion of the membrane-targeting
      domain of the HIV-1 matrix (MA) protein that altered the virus assembly and
      budding site to CD63(+)/Lamp-1-positive intracellular compartments resulted in
      lower levels of virion incorporation of GM3 and attenuation of virus capture by
      MDCs. Furthermore, MDC-mediated capture and transmission of MA mutant viruses to
      T cells were decreased, suggesting that HIV-1 acquires GSLs via budding from the
      plasma membrane to access the MDC-dependent trans infection pathway.
      Interestingly, MDC-mediated capture of Nipah and Hendra virus (recently emerged
      zoonotic paramyxoviruses) M (matrix) protein-derived virus-like particles that
      bud from GSL-enriched plasma membrane microdomains was also dependent on
      interactions between virion-incorporated GSLs and CD169. Moreover, capture and
      transfer of Nipah virus envelope glycoprotein-pseudotyped lentivirus particles by
      MDCs were severely attenuated upon depletion of GSLs from virus particles. These
      results suggest that GSL incorporation into virions is critical for the
      interaction of diverse enveloped RNA viruses with DCs and that the GSL-CD169
      recognition nexus might be a conserved viral mechanism of parasitization of DC
      functions for systemic virus dissemination. IMPORTANCE: Dendritic cells (DCs) can
      capture HIV-1 particles and transfer captured virus particles to T cells without
      establishing productive infection in DCs, a mechanism of HIV-1 trans infection.
      We have recently identified CD169-mediated recognition of GM3, a host-derived
      glycosphingolipid (GSL) incorporated into the virus particle membrane, as the
      receptor and ligand for the DC-HIV trans infection pathway. In this study, we
      have identified the matrix (MA) domain of Gag to be the viral determinant that
      governs incorporation of GM3 into HIV-1 particles, a previously unappreciated
      function of the HIV-1 MA. In addition, we demonstrate that the GSL-CD169
      dependent trans infection pathway is also utilized as a dissemination mechanism
      by henipaviruses. GSL incorporation in henipaviruses was also dependent on the
      viral capsid (M) protein-directed assembly and budding from GSL-enriched lipid
      microdomains. These findings provide evidence of a conserved mechanism of
      retrovirus and henipavirus parasitization of cell-to-cell recognition pathways
      for systemic virus dissemination.

PMID- 24872581
TI  - Functional annotation of Cotesia congregata bracovirus: identification of viral
      genes expressed in parasitized host immune tissues.
AB  - Bracoviruses (BVs) from the Polydnaviridae family are symbiotic viruses used as
      biological weapons by parasitoid wasps to manipulate lepidopteran host physiology
      and induce parasitism success. BV particles are produced by wasp ovaries and
      injected along with the eggs into the caterpillar host body, where viral gene
      expression is necessary for wasp development. Recent sequencing of the proviral
      genome of Cotesia congregata BV (CcBV) identified 222 predicted virulence genes
      present on 35 proviral segments integrated into the wasp genome. To date, the
      expressions of only a few selected candidate virulence genes have been studied in
      the caterpillar host, and we lacked a global vision of viral gene expression. In
      this study, a large-scale transcriptomic analysis by 454 sequencing of two immune
      tissues (fat body and hemocytes) of parasitized Manduca sexta caterpillar hosts
      allowed the detection of expression of 88 CcBV genes expressed 24 h after the
      onset of parasitism. We linked the expression profiles of these genes to several
      factors, showing that different regulatory mechanisms control viral gene
      expression in the host. These factors include the presence of signal peptides in
      encoded proteins, diversification of promoter regions, and, more surprisingly,
      gene position on the proviral genome. Indeed, most genes for which expression
      could be detected are localized in particular proviral regions globally producing
      higher numbers of circles. Moreover, this polydnavirus (PDV) transcriptomic
      analysis also reveals that a majority of CcBV genes possess at least one intron
      and an arthropod transcription start site, consistent with an insect origin of
      these virulence genes. IMPORTANCE: Bracoviruses (BVs) are symbiotic
      polydnaviruses used by parasitoid wasps to manipulate lepidopteran host
      physiology, ensuring wasp offspring survival. To date, the expressions of only a
      few selected candidate BV virulence genes have been studied in caterpillar hosts.
      We performed a large-scale analysis of BV gene expression in two immune tissues
      of Manduca sexta caterpillars parasitized by Cotesia congregata wasps. Genes for
      which expression could be detected corresponded to genes localized in particular
      regions of the viral genome globally producing higher numbers of circles. Our
      study thus brings an original global vision of viral gene expression and paves
      the way to the determination of the regulatory mechanisms enabling the expression
      of BV genes in targeted organisms, such as major insect pests. In addition, we
      identify sequence features suggesting that most BV virulence genes were acquired
      from insect genomes.

PMID- 24872582
TI  - Uracil DNA glycosylase BKRF3 contributes to Epstein-Barr virus DNA replication
      through physical interactions with proteins in viral DNA replication complex.
AB  - Epstein-Barr virus (EBV) BKRF3 shares sequence homology with members of the
      uracil-N-glycosylase (UNG) protein family and has DNA glycosylase activity. Here,
      we explored how BKRF3 participates in the DNA replication complex and contributes
      to viral DNA replication. Exogenously expressed Flag-BKRF3 was distributed mostly
      in the cytoplasm, whereas BKRF3 was translocated into the nucleus and colocalized
      with the EBV DNA polymerase BALF5 in the replication compartment during EBV lytic
      replication. The expression level of BKRF3 increased gradually during viral
      replication, coupled with a decrease of cellular UNG2, suggesting BKRF3 enzyme
      activity compensates for UNG2 and ensures the fidelity of viral DNA replication.
      In immunoprecipitation-Western blotting, BKRF3 was coimmuno-precipitated with
      BALF5, the polymerase processivity factor BMRF1, and the immediate-early
      transactivator Rta. Coexpression of BMRF1 appeared to facilitate the nuclear
      targeting of BKRF3 in immunofluorescence staining. Residues 164 to 255 of BKRF3
      were required for interaction with Rta and BALF5, whereas residues 81 to 166 of
      BKRF3 were critical for BMRF1 interaction in glutathione S-transferase (GST)
      pulldown experiments. Viral DNA replication was defective in cells harboring
      BKRF3 knockout EBV bacmids. In complementation assays, the catalytic mutant
      BKRF3(Q90L,D91N) restored viral DNA replication, whereas the leucine loop mutant
      BKRF3(H213L) only partially rescued viral DNA replication, coupled with a reduced
      ability to interact with the viral DNA polymerase and Rta. Our data suggest that
      BKRF3 plays a critical role in viral DNA synthesis predominantly through its
      interactions with viral proteins in the DNA replication compartment, while its
      enzymatic activity may be supplementary for uracil DNA glycosylase (UDG) function
      during virus replication. IMPORTANCE: Catalytic activities of both cellular UDG
      UNG2 and viral UDGs contribute to herpesviral DNA replication. To ensure that the
      enzyme activity executes at the right time and the right place in DNA replication
      forks, complex formation with other components in the DNA replication machinery
      provides an important regulation for UDG function. In this study, we provide the
      mechanism for EBV UDG BKRF3 nuclear targeting and the interacting domains of
      BKRF3 with viral DNA replication proteins. Through knockout and complementation
      approaches, we further demonstrate that in addition to UDG activity, the
      interaction of BKRF3 with viral proteins in the replication compartment is
      crucial for efficient viral DNA replication.

PMID- 24872583
TI  - Progression from IgD+ IgM+ to isotype-switched B cells is site specific during
      coronavirus-induced encephalomyelitis.
AB  - Various infections in the central nervous system (CNS) trigger B cell
      accumulation; however, the relative dynamics between viral replication and
      alterations in distinct B cell subsets are largely unknown. Using a glia-tropic
      coronavirus infection, which is initiated in the brain but rapidly spreads to and
      predominantly persists in the spinal cord, this study characterizes longitudinal
      changes in B cell subsets at both infected anatomical sites. The phase of T cell
      dependent, antibody-independent control of infectious virus was associated with a
      similar recruitment of naive/early-activated IgD(+) IgM(+) B cells into both the
      brain and spinal cord. This population was progressively replaced by CD138(-)
      IgD(-) IgM(+) B cells, isotype-switched CD138(-) IgD(-) IgM(-) memory B cells
      (B(mem)), and CD138(+) antibody-secreting cells (ASC). A more rapid transition to
      B(mem) and ASC in spinal cord than in brain was associated with higher levels of
      persisting viral RNA and transcripts encoding factors promoting B cell migration,
      differentiation, and survival. The results demonstrate that naive/early-activated
      B cells are recruited early during coronavirus CNS infection but are subsequently
      replaced by more differentiated B cells. Furthermore, viral persistence, even at
      low levels, is a driving force for accumulation of isotype-switched B(mem) and
      ASC. IMPORTANCE: Acute and chronic human CNS infections are associated with an
      accumulation of heterogeneous B cell subsets; however, their influence on viral
      load and disease is unclear. Using a glia-tropic coronavirus model, we
      demonstrate that the accumulation of B cells ranging from early-activated to
      isotype-switched differentiation stages is both temporally and spatially
      orchestrated. Acutely infected brains and spinal cords indiscriminately recruit a
      homogeneous population of early-activated B cells, which is progressively
      replaced by diverse, more differentiated subsets. The latter process is
      accelerated by elevated proinflammatory responses associated with viral
      persistence. The results imply that early-recruited B cells do not have antiviral
      function but may contribute to the inflammatory environment or act as antigen
      presenting cells. Moreover, CNS viral persistence is a driving force promoting
      differentiated B cells with protective potential.

PMID- 24872584
TI  - Cryo-electron microscopy structure of lactococcal siphophage 1358 virion.
AB  - Lactococcus lactis, a Gram(+) lactic acid-producing bacterium used for the
      manufacture of several fermented dairy products, is subject to infection by
      diverse virulent tailed phages, leading to industrial fermentation failures. This
      constant viral risk has led to a sustained interest in the study of their
      biology, diversity, and evolution. Lactococcal phages now constitute a wide
      ensemble of at least 10 distinct genotypes within the Caudovirales order, many of
      them belonging to the Siphoviridae family. Lactococcal siphophage 1358, currently
      the only member of its group, displays a noticeably high genomic similarity to
      some Listeria phages as well as a host range limited to a few L. lactis strains.
      These genomic and functional characteristics stimulated our interest in this
      phage. Here, we report the cryo-electron microscopy structure of the complete
      1358 virion. Phage 1358 exhibits noteworthy features, such as a capsid with
      dextro handedness and protruding decorations on its capsid and tail. Observations
      of the baseplate of virion particles revealed at least two conformations, a
      closed and an open, activated form. Functional assays uncovered that the
      adsorption of phage 1358 to its host is Ca(2+) independent, but this cation is
      necessary to complete its lytic cycle. Taken together, our results provide the
      complete structural picture of a unique lactococcal phage and expand our
      knowledge on the complex baseplate of phages of the Siphoviridae family.
      IMPORTANCE: Phages of Lactococcus lactis are investigated mainly because they are
      sources of milk fermentation failures in the dairy industry. Despite the
      availability of several antiphage measures, new phages keep emerging in this
      ecosystem. In this study, we provide the cryo-electron microscopy reconstruction
      of a unique lactococcal phage that possesses genomic similarity to particular
      Listeria phages and has a host range restricted to only a minority of L. lactis
      strains. The capsid of phage 1358 displays the almost unique characteristic of
      being dextro handed. Its capsid and tail exhibit decorations that we assigned to
      nonspecific sugar binding modules. We observed the baseplate of 1358 in two
      conformations, a closed and an open form. We also found that the adsorption to
      its host, but not infection, is Ca(2+) independent. Overall, this study advances
      our understanding of the adhesion mechanisms of siphophages.

PMID- 24872585
TI  - Downregulation of interleukin-18-mediated cell signaling and interferon gamma
      expression by the hepatitis B virus e antigen.
AB  - The mechanisms by which hepatitis B virus (HBV) establishes and maintains chronic
      hepatitis B infection (CHB) are poorly defined. Innate immune responses play an
      important role in reducing HBV replication and pathogenesis. HBV has developed
      numerous mechanisms to escape these responses, including the production of the
      secreted hepatitis B e antigen (HBeAg), which has been shown to regulate
      antiviral toll-like receptor (TLR) and interleukin-1 (IL-1) signaling. IL-18 is a
      related cytokine that inhibits HBV replication in hepatoma cell lines and in the
      liver through the induction of gamma interferon (IFN-gamma) by NK cells and T
      cells. We hypothesized that HBV or HBV proteins inhibit IFN-gamma expression by
      NK cells as an accessory immunomodulatory function. We show that HBeAg protein
      inhibits the NF-kappaB pathway and thereby downregulates NK cell IFN-gamma
      expression. Additionally, IFN-gamma expression was significantly inhibited by
      exposure to serum from individuals with HBeAg-positive but not HBeAg-negative
      chronic HBV infection. Further, we show that the HBeAg protein suppresses IL-18
      mediated NF-kappaB signaling in NK and hepatoma cells via modulation of the NF
      kappaB pathway. Together, these findings show that the HBeAg inhibits IL-18
      signaling and IFN-gamma expression, which may play an important role in the
      establishment and/or maintenance of persistent HBV infection. IMPORTANCE: It is
      becoming increasingly apparent that NK cells play a role in the establishment
      and/or maintenance of chronic hepatitis B infection. The secreted HBeAg is an
      important regulator of innate and adaptive immune responses. We now show that the
      HBeAg downregulates NK cell-mediated IFN-gamma production and IL-18 signaling,
      which may contribute to the establishment of infection and/or viral persistence.
      Our findings build on previous studies showing that the HBeAg also suppresses the
      TLR and IL-1 signaling pathways, suggesting that this viral protein is a key
      regulator of antiviral innate immune responses.

PMID- 24872586
TI  - Dependence of coronavirus RNA replication on an NH2-terminal partial
      nonstructural protein 1 in cis.
AB  - Genomes of positive (+)-strand RNA viruses use cis-acting signals to direct both
      translation and replication. Here we examine two 5'-proximal cis-replication
      signals of different character in a defective interfering (DI) RNA of the bovine
      coronavirus (BCoV) that map within a 322-nucleotide (nt) sequence (136 nt from
      the genomic 5' untranslated region and 186 nt from the nonstructural protein 1
      [nsp1]-coding region) not found in the otherwise-identical nonreplicating
      subgenomic mRNA7 (sgmRNA7). The natural DI RNA is structurally a fusion of the
      two ends of the BCoV genome that results in a single open reading frame between a
      partial nsp1-coding region and the entire N gene. (i) In the first examination,
      mutation analyses of a recently discovered long-range RNA-RNA base-paired
      structure between the 5' untranslated region and the partial nsp1-coding region
      showed that it, possibly in concert with adjacent stem-loops, is a cis-acting
      replication signal in the (+) strand. We postulate that the higher-order
      structure promotes (+)-strand synthesis. (ii) In the second examination, analyses
      of multiple frame shifts, truncations, and point mutations within the partial
      nsp1-coding region showed that synthesis of a PEFP core amino acid sequence
      within a group A lineage betacoronavirus-conserved NH2-proximal WAPEFPWM domain
      is required in cis for DI RNA replication. We postulate that the nascent protein,
      as part of an RNA-associated translating complex, acts to direct the DI RNA to a
      critical site, enabling RNA replication. We suggest that these results have
      implications for viral genome replication and explain, in part, why coronavirus
      sgmRNAs fail to replicate. IMPORTANCE: cis-Acting RNA and protein structures that
      regulate (+)-strand RNA virus genome synthesis are potential sites for blocking
      virus replication. Here we describe two: a previously suspected 5'-proximal long
      range higher-order RNA structure and a novel nascent NH2-terminal protein
      component of nsp1 that are common among betacoronaviruses of group A lineage.

PMID- 24872587
TI  - Nucleotide oligomerization and binding domain 2-dependent dendritic cell
      activation is necessary for innate immunity and optimal CD8+ T Cell responses to
      influenza A virus infection.
AB  - Nucleotide oligomerization and binding domain (NOD)-like receptors (NLRs) are
      important in the innate immune response to viral infection. Recent findings have
      implicated NLRP3, NOD2, and NLRX1 as important players in the innate antiviral
      response, but their roles in the generation of adaptive immunity to viruses are
      less clear. We demonstrate here that NOD2 is critical for both innate and
      adaptive immune responses necessary for controlling viral replication and
      survival during influenza A virus (IAV) infection. Nod2(-/-) mice have reduced
      beta interferon (IFN-beta) levels and fewer activated dendritic cells (DCs), and
      the DCs are more prone to cell death in the lungs of Nod2(-/-) mice during IAV
      infection. In agreement with the role for DCs in priming adaptive immunity, the
      generation of virus-specific CD8(+) T cells and their activation and production
      of IFN-gamma were lower in Nod2(-/-) mice. Furthermore, Nod2(-/-) DCs, when
      cocultured with T cells in vitro, have a lower costimulatory capacity. Thus,
      Nod2(-/-) DCs are unable to efficiently prime CD8(+) T cells. These findings
      demonstrate that Nod2 is critical for the generation of both innate and adaptive
      immune responses necessary for controlling IAV infection. IMPORTANCE: The innate
      immune system is the host's first line of defense against invading pathogens and
      is also necessary for alerting and activating T and B cells to initiate the
      adaptive immune response. We demonstrate here that the innate immune receptor
      NOD2 is required for the production of antiviral type I interferons and the
      activation and survival of dendritic cells that, in turn, alert T cells to the
      presence of influenza A virus infection. In mice that are missing NOD2,
      interferon levels are lower, and the CD8(+) T cell response is impaired. As a
      result, the animals cannot control virus replication in their lungs as
      efficiently. This discovery helps us understand how the body naturally responds
      to virus infection and may help in the development of vaccines that use NOD2 to
      stimulate the CD8(+) T cell response, thus providing better protection against
      influenza A virus infection.

PMID- 24872588
TI  - Influenza virus PB1 and neuraminidase gene segments can cosegregate during
      vaccine reassortment driven by interactions in the PB1 coding region.
AB  - Egg-grown influenza vaccine yields are maximized by infection with a seed virus
      produced by "classical reassortment" of a seasonal isolate with a highly egg
      adapted strain. Seed viruses are selected based on a high-growth phenotype and
      the presence of the seasonal hemagglutinin (HA) and neuraminidase (NA) surface
      antigens. Retrospective analysis of H3N2 vaccine seed viruses indicated that,
      unlike other internal proteins that were predominantly derived from the high
      growth parent A/Puerto Rico/8/34 (PR8), the polymerase subunit PB1 could be
      derived from either parent depending on the seasonal strain. We have recently
      shown that A/Udorn/307/72 (Udorn) models a seasonal isolate that yields
      reassortants bearing the seasonal PB1 gene. This is despite the fact that the
      reverse genetics-derived virus that includes Udorn PB1 with Udorn HA and NA on a
      PR8 background has inferior growth compared to the corresponding virus with PR8
      PB1. Here we use competitive plasmid transfections to investigate the mechanisms
      driving selection of a less fit virus and show that the Udorn PB1 gene segment
      cosegregates with the Udorn NA gene segment. Analysis of chimeric PB1 genes
      revealed that the coselection of NA and PB1 segments was not directed through the
      previously identified packaging sequences but through interactions involving the
      internal coding region of the PB1 gene. This study identifies associations
      between viral genes that can direct selection in classical reassortment for
      vaccine production and which may also be of relevance to the gene constellations
      observed in past antigenic shift events where creation of a pandemic virus has
      involved reassortment. IMPORTANCE: Influenza vaccine must be produced and
      administered in a timely manner in order to provide protection during the winter
      season, and poor-growing vaccine seed viruses can compromise this process. To
      maximize vaccine yields, manufacturers create hybrid influenza viruses with gene
      segments encoding the surface antigens from a seasonal virus isolate, important
      for immunity, and others from a virus with high growth properties. This involves
      coinfection of cells with both parent viruses and selection of dominant progeny
      bearing the seasonal antigens. We show that this method of creating hybrid
      viruses does not necessarily select for the best yielding virus because
      preferential pairing of gene segments when progeny viruses are produced
      determines the genetic makeup of the hybrids. This not only has implications for
      how hybrid viruses are selected for vaccine production but also sheds light on
      what drives and limits hybrid gene combinations that arise in nature, leading to
      pandemics.

PMID- 24872589
TI  - Human T-cell leukemia virus type 3 (HTLV-3) and HTLV-4 antisense-transcript
      encoded proteins interact and transactivate Jun family-dependent transcription
      via their atypical bZIP motif.
AB  - Human T-cell leukemia virus types 3 and 4 (HTLV-3 and HTLV-4) are recently
      isolated retroviruses. We have previously characterized HTLV-3- and HTLV-4
      encoded antisense genes, termed APH-3 and APH-4, respectively, which, in contrast
      to HBZ, the HTLV-1 homologue, do not contain a typical bZIP domain (M. Larocque E
      Halin, S. Landry, S. J. Marriott, W. M. Switzer, and B. Barbeau, J. Virol.
      85:12673-12685, 2011, doi:10.1128/JVI.05296-11). As HBZ differentially modulates
      the transactivation potential of various Jun family members, the effect of APH-3
      and APH-4 on JunD-, c-Jun-, and JunB-mediated transcriptional activation was
      investigated. We first showed that APH-3 and APH-4 upregulated the
      transactivation potential of all tested Jun family members. Using an human
      telomerase catalytic subunit (hTERT) promoter construct, our results also
      highlighted that, unlike HBZ, which solely modulates hTERT expression via JunD,
      both APH-3 and APH-4 acted positively on the transactivation of the hTERT
      promoter mediated by tested Jun factors. Coimmunoprecipitation experiments
      demonstrated that these Jun proteins interacted with APH-3 and APH-4. Although no
      activation domain was identified for APH proteins, the activation domain of c-Jun
      was very important in the observed upregulation of its activation potential. We
      further showed that APH-3 and APH-4 required their putative bZIP-like domains and
      corresponding leucine residues for interaction and modulation of the
      transactivation potential of Jun factors. Our results demonstrate that HTLV
      encoded antisense proteins behave differently, and that the bZIP-like domains of
      both APH-3 and APH-4 have retained their interaction potential for Jun members.
      These studies are important in assessing the differences between HBZ and other
      antisense proteins, which might further contribute to determining the role of HBZ
      in HTLV-1-associated diseases. IMPORTANCE HBZ, the antisense transcript-encoded
      protein from HTLV-1, is now well recognized as a potential factor for adult T
      cell leukemia/lymphoma development. In order to better appreciate the mechanism
      of action of HBZ, comparison to antisense proteins from other HTLV viruses is
      important. Little is known in relation to the seemingly nonpathogenic HTLV-3 and
      HTLV-4 viruses, and studies of their antisense proteins are limited to our
      previously reported study (M. Larocque E Halin, S. Landry, S. J. Marriott, W. M.
      Switzer, and B. Barbeau, J. Virol. 85:12673-12685, 2011, doi:10.1128/JVI.05296
      11). Here, we demonstrate that Jun transcription factors are differently affected
      by APH-3 and APH-4 compared to HBZ. These intriguing findings suggest that these
      proteins act differently on viral replication but also on cellular gene
      expression, and that highlighting their differences of action might lead to
      important information allowing us to understand the link between HTLV-1 HBZ and
      ATL in infected individuals. 

PMID- 24872590
TI  - Restriction of HIV-1 by rhesus TRIM5alpha is governed by alpha helices in the
      Linker2 region.
AB  - TRIM5alpha proteins are a potent barrier to the cross-species transmission of
      retroviruses. TRIM5alpha proteins exhibit an ability to self-associate at many
      levels, ultimately leading to the formation of protein assemblies with hexagonal
      symmetry in vitro and cytoplasmic assemblies when expressed in cells. However,
      the role of these assemblies in restriction, the determinants that mediate their
      formation, and the organization of TRIM5alpha molecules within these assemblies
      have remained unclear. Here we show that alpha-helical elements within the
      Linker2 region of rhesus macaque TRIM5alpha govern the ability to form
      cytoplasmic assemblies in cells and restrict HIV-1 infection. Mutations that
      reduce alpha-helix formation by the Linker2 region disrupt assembly and
      restriction. More importantly, mutations that enhance the alpha-helical content
      of the Linker2 region, relative to the wild-type protein, also exhibit an
      increased ability to form cytoplasmic assemblies and restrict HIV-1 infection.
      Molecular modeling of the TRIM5alpha dimer suggests a model in which alpha
      helical elements within the Linker2 region dock to alpha-helices of the coiled
      coil domain, likely establishing proper orientation and spacing of protein
      domains necessary for assembly and restriction. Collectively, these studies
      provide critical insight into the determinants governing TRIM5alpha assembly and
      restriction and demonstrate that the antiviral potency of TRIM5alpha proteins can
      be significantly increased without altering the affinity of SPRY/capsid binding.
      IMPORTANCE: Many members of the tripartite motif (TRIM) family of proteins act as
      restriction factors that directly inhibit viral infection and activate innate
      immune signaling pathways. Another common feature of TRIM proteins is the ability
      to form protein assemblies in the nucleus or the cytoplasm. However, the
      determinants in TRIM proteins required for assembly and the degree to which
      assembly affects TRIM protein function have been poorly understood. Here we show
      that alpha helices in the Linker2 (L2) region of rhesus TRIM5alpha govern
      assembly and restriction of HIV-1 infection. Helix-disrupting mutations disrupt
      the assembly and restriction of HIV-1, while helix-stabilizing mutations enhance
      assembly and restriction relative to the wild-type protein. Circular dichroism
      analysis suggests that that the formation of this helical structure is supported
      by intermolecular interactions with the coiled-coil (CC) domain in the CCL2
      dimer. These studies reveal a novel mechanism by which the antiviral activity of
      TRIM5alpha proteins can be regulated and provide detailed insight into the
      assembly determinants of TRIM family proteins.

PMID- 24872591
TI  - Porcine epidemic diarrhea virus nucleocapsid protein antagonizes beta interferon
      production by sequestering the interaction between IRF3 and TBK1.
AB  - Porcine epidemic diarrhea virus (PEDV), a porcine enteropathogenic coronavirus,
      causes lethal watery diarrhea in piglets and results in large economic losses in
      many Asian and European countries. A large-scale outbreak of porcine epidemic
      diarrhea occurred in China in 2010, and the virus emerged in the United States in
      2013 and spread rapidly, posing significant economic and public health concerns.
      Previous studies have shown that PEDV infection inhibits the synthesis of type I
      interferon (IFN), and viral papain-like protease 2 has been identified as an IFN
      antagonist. In this study, we found that the PEDV-encoded nucleocapsid (N)
      protein also inhibits Sendai virus-induced IFN-beta production, IFN-stimulated
      gene expression, and activation of the transcription factors IFN regulatory
      factor 3 (IRF3) and NF-kappaB. We also found that N protein significantly impedes
      the activation of the IFN-beta promoter stimulated by TBK1 or its upstream
      molecules (RIG-I, MDA5, IPS-1, and TRAF3) but does not counteract its activation
      by IRF3. A detailed analysis revealed that the PEDV N protein targets TBK1 by
      direct interaction and that this binding sequesters the association between TBK1
      and IRF3, which in turn inhibits both IRF3 activation and type I IFN production.
      Together, our findings demonstrate a new mechanism evolved by PEDV to circumvent
      the host's antiviral immunity. IMPORTANCE: PEDV has received increasing attention
      since the emergence of a PEDV variant in China and the United States. Here, we
      identify nucleocapsid (N) protein as a novel PEDV-encoded interferon (IFN)
      antagonist and demonstrate that N protein antagonizes IFN production by
      sequestering the interaction between IRF3 and TBK1, a critical step in type I IFN
      signaling. This adds another layer of complexity to the immune evasion strategies
      evolved by this economically important viral pathogen. An understanding of its
      immune evasion mechanism may direct us to novel therapeutic targets and more
      effective vaccines against PEDV infection.

PMID- 24872593
TI  - Activation of c-jun N-terminal kinase upon influenza A virus (IAV) infection is
      independent of pathogen-related receptors but dependent on amino acid sequence
      variations of IAV NS1.
AB  - A hallmark cell response to influenza A virus (IAV) infections is the
      phosphorylation and activation of c-jun N-terminal kinase (JNK). However, so far
      it is not fully clear which molecules are involved in the activation of JNK upon
      IAV infection. Here, we report that the transfection of influenza viral-RNA
      induces JNK in a retinoic acid-inducible gene I (RIG-I)-dependent manner.
      However, neither RIG-I-like receptors nor MyD88-dependent Toll-like receptors
      were found to be involved in the activation of JNK upon IAV infection. Viral JNK
      activation may be blocked by addition of cycloheximide and heat shock protein
      inhibitors during infection, suggesting that the expression of an IAV-encoded
      protein is responsible for JNK activation. Indeed, the overexpression of
      nonstructural protein 1 (NS1) of certain IAV subtypes activated JNK, whereas
      those of some other subtypes failed to activate JNK. Site-directed mutagenesis
      experiments using NS1 of the IAV H7N7, H5N1, and H3N2 subtypes identified the
      amino acid residue phenylalanine (F) at position 103 to be decisive for JNK
      activation. Cleavage- and polyadenylation-specific factor 30 (CPSF30), whose
      binding to NS1 is stabilized by the amino acids F103 and M106, is not involved in
      JNK activation. Conclusively, subtype-specific sequence variations in the IAV NS1
      protein result in subtype-specific differences in JNK signaling upon IAV
      infection. IMPORTANCE: Influenza A virus (IAV) infection leads to the activation
      or modulation of multiple signaling pathways. Here, we demonstrate for the first
      time that the c-jun N-terminal kinase (JNK), a long-known stress-activated
      mitogen-activated protein (MAP) kinase, is activated by RIG-I when cells are
      treated with IAV RNA. However, at the same time, nonstructural protein 1 (NS1) of
      IAV has an intrinsic JNK-activating property that is dependent on IAV subtype
      specific amino acid variations around position 103. Our findings identify two
      different and independent pathways that result in the activation of JNK in the
      course of an IAV infection.

PMID- 24872592
TI  - Regulation of the human endogenous retrovirus K (HML-2) transcriptome by the HIV
      1 Tat protein.
AB  - Approximately 8% of the human genome is made up of endogenous retroviral
      sequences. As the HIV-1 Tat protein activates the overall expression of the human
      endogenous retrovirus type K (HERV-K) (HML-2), we used next-generation sequencing
      to determine which of the 91 currently annotated HERV-K (HML-2) proviruses are
      regulated by Tat. Transcriptome sequencing of total RNA isolated from Tat- and
      vehicle-treated peripheral blood lymphocytes from a healthy donor showed that Tat
      significantly activates expression of 26 unique HERV-K (HML-2) proviruses,
      silences 12, and does not significantly alter the expression of the remaining
      proviruses. Quantitative reverse transcription-PCR validation of the sequencing
      data was performed on Tat-treated PBLs of seven donors using provirus-specific
      primers and corroborated the results with a substantial degree of quantitative
      similarity. IMPORTANCE: The expression of HERV-K (HML-2) is tightly regulated but
      becomes markedly increased following infection with HIV-1, in part due to the HIV
      1 Tat protein. The findings reported here demonstrate the complexity of the
      genome-wide regulation of HERV-K (HML-2) expression by Tat. This work also
      demonstrates that although HERV-K (HML-2) proviruses in the human genome are
      highly similar in terms of DNA sequence, modulation of the expression of specific
      proviruses in a given biological situation can be ascertained using next
      generation sequencing and bioinformatics analysis.

PMID- 24872596
TI  - Personal utility in genomic testing: is there such a thing?
AB  - In ethical and regulatory discussions on new applications of genomic testing
      technologies, the notion of 'personal utility' has been mentioned repeatedly. It
      has been used to justify direct access to commercially offered genomic testing or
      feedback of individual research results to research or biobank participants.
      Sometimes research participants or consumers claim a right to genomic information
      with an appeal to personal utility. As of yet, no systematic account of the
      umbrella notion of personal utility has been given. This paper offers a
      definition of personal utility that places it in the middle of the spectrum
      between clinical utility and personal perceptions of utility, and that
      acknowledges its normative charge. The paper discusses two perspectives on
      personal utility, the healthcare perspective and the consumer perspective, and
      argues that these are too narrow and too wide, respectively. Instead, it proposes
      a normative definition of personal utility that postulates information and
      potential use as necessary conditions of utility. This definition entails that
      perceived utility does not equal personal utility, and that expert judgment may
      be necessary to help determine whether a genomic test can have personal utility
      for someone. Two examples of genomic tests are presented to illustrate the
      discrepancies between perceived utility and our proposed definition of personal
      utility. The paper concludes that while there is room for the notion of personal
      utility in the ethical evaluation and regulation of genomic tests, the
      justificatory role of personal utility is not unlimited. For in the absence of
      clinical validity and reasonable potential use of information, there is no
      personal utility. 

PMID- 24872594
TI  - Deciphering thylakoid sub-compartments using a mass spectrometry-based approach.
AB  - Photosynthesis has shaped atmospheric and ocean chemistries and probably changed
      the climate as well, as oxygen is released from water as part of the
      photosynthetic process. In photosynthetic eukaryotes, this process occurs in the
      chloroplast, an organelle containing the most abundant biological membrane, the
      thylakoids. The thylakoids of plants and some green algae are structurally
      inhomogeneous, consisting of two main domains: the grana, which are piles of
      membranes gathered by stacking forces, and the stroma-lamellae, which are
      unstacked thylakoids connecting the grana. The major photosynthetic complexes are
      unevenly distributed within these compartments because of steric and
      electrostatic constraints. Although proteomic analysis of thylakoids has been
      instrumental to define its protein components, no extensive proteomic study of
      subthylakoid localization of proteins in the BBY (grana) and the stroma-lamellae
      fractions has been achieved so far. To fill this gap, we performed a complete
      survey of the protein composition of these thylakoid subcompartments using
      thylakoid membrane fractionations. We employed semiquantitative proteomics
      coupled with a data analysis pipeline and manual annotation to differentiate
      genuine BBY and stroma-lamellae proteins from possible contaminants. About 300
      thylakoid (or potentially thylakoid) proteins were shown to be enriched in either
      the BBY or the stroma-lamellae fractions. Overall, present findings corroborate
      previous observations obtained for photosynthetic proteins that used nonproteomic
      approaches. The originality of the present proteomic relies in the identification
      of photosynthetic proteins whose differential distribution in the thylakoid
      subcompartments might explain already observed phenomenon such as LHCII docking.
      Besides, from the present localization results we can suggest new molecular
      actors for photosynthesis-linked activities. For instance, most PsbP-like
      subunits being differently localized in stroma-lamellae, these proteins could be
      linked to the PSI-NDH complex in the context of cyclic electron flow around PSI.
      In addition, we could identify about a hundred new likely minor thylakoid (or
      chloroplast) proteins, some of them being potential regulators of the chloroplast
      physiology. 

PMID- 24872598
TI  - STOCHASTIC INTEGRATION FOR TEMPERED FRACTIONAL BROWNIAN MOTION.
AB  - Tempered fractional Brownian motion is obtained when the power law kernel in the
      moving average representation of a fractional Brownian motion is multiplied by an
      exponential tempering factor. This paper develops the theory of stochastic
      integrals for tempered fractional Brownian motion. Along the way, we develop some
      basic results on tempered fractional calculus.

PMID- 24872597
TI  - Multilevel sparse functional principal component analysis.
AB  - We consider analysis of sparsely sampled multilevel functional data, where the
      basic observational unit is a function and data have a natural hierarchy of basic
      units. An example is when functions are recorded at multiple visits for each
      subject. Multilevel functional principal component analysis (MFPCA; Di et al.
      2009) was proposed for such data when functions are densely recorded. Here we
      consider the case when functions are sparsely sampled and may contain only a few
      observations per function. We exploit the multilevel structure of covariance
      operators and achieve data reduction by principal component decompositions at
      both between and within subject levels. We address inherent methodological
      differences in the sparse sampling context to: 1) estimate the covariance
      operators; 2) estimate the functional principal component scores; 3) predict the
      underlying curves. Through simulations the proposed method is able to discover
      dominating modes of variations and reconstruct underlying curves well even in
      sparse settings. Our approach is illustrated by two applications, the Sleep Heart
      Health Study and eBay auctions.

PMID- 24872595
TI  - Profiling the secretome and extracellular proteome of the potato late blight
      pathogen Phytophthora infestans.
AB  - Oomycetes are filamentous organisms that cause notorious diseases, several of
      which have a high economic impact. Well known is Phytophthora infestans, the
      causal agent of potato late blight. Previously, in silico analyses of the genome
      and transcriptome of P. infestans resulted in the annotation of a large number of
      genes encoding proteins with an N-terminal signal peptide. This set is
      collectively referred to as the secretome and comprises proteins involved in, for
      example, cell wall growth and modification, proteolytic processes, and the
      promotion of successful invasion of plant cells. So far, proteomic profiling in
      oomycetes was primarily focused on subcellular, intracellular or cell wall
      fractions; the extracellular proteome has not been studied systematically. Here
      we present the first comprehensive characterization of the in vivo secretome and
      extracellular proteome of P. infestans. We have used mass spectrometry to analyze
      P. infestans proteins present in seven different growth media with mycelial
      cultures and this resulted in the consistent identification of over two hundred
      proteins. Gene ontology classification pinpointed proteins involved in cell wall
      modifications, pathogenesis, defense responses, and proteolytic processes.
      Moreover, we found members of the RXLR and CRN effector families as well as
      several proteins lacking an obvious signal peptide. The latter were confirmed to
      be bona fide extracellular proteins and this suggests that, similar to other
      organisms, oomycetes exploit non-conventional secretion mechanisms to transfer
      certain proteins to the extracellular environment. 

PMID- 24872600
TI  - Immune-endocrine cross-talk in reproductive biology and pathology.

PMID- 24872599
TI  - Animal models of C-reactive protein.
AB  - As the main theme of this special issue, CRP not only is an inflammatory marker
      but also has diverse biological functions associated with different diseases. To
      investigate CRP's physiologies and their relationship with human pathological
      significance, it is essential to use appropriate animal models for translational
      research. The most popular models for the study of CRP are transgenic mice.
      However, researchers should be careful when extrapolating the findings derived
      from these animal models. This review will discuss the current concerns on CRP
      transgenic mice and rabbits. 

PMID- 24872602
TI  - Patient safety in an environment of rapidly advancing technology in radiation
      therapy.

PMID- 24872601
TI  - Effects of antisense oligonucleotides against C-reactive protein on the
      development of atherosclerosis in WHHL rabbits.
AB  - Increased plasma levels of C-reactive protein (CRP) are closely associated with
      cardiovascular diseases, but whether CRP is directly involved in the pathogenesis
      of atherosclerosis is still under debate. Many controversial and contradictory
      results using transgenic mice and rabbits have been published but it is also
      unclear whether CRP lowering can be used for the treatment of atherosclerosis. In
      the current study, we examined the effects of the rabbit CRP antisense
      oligonucleotides (ASO) on the development of atherosclerosis in WHHL rabbits. CRP
      ASO treatment led to a significant reduction of plasma CRP levels; however, both
      aortic and coronary atherosclerotic lesions were not significantly changed
      compared to those of control WHHL rabbits. These results suggest that inhibition
      of plasma CRP does not affect the development of atherosclerosis in WHHL rabbits.

PMID- 24872603
TI  - A dose homogeneity and conformity evaluation between ViewRay and pinnacle-based
      linear accelerator IMRT treatment plans.
AB  - ViewRay, a novel technology providing soft-tissue imaging during radiotherapy is
      investigated for treatment planning capabilities assessing treatment plan dose
      homogeneity and conformity compared with linear accelerator plans. ViewRay offers
      both adaptive radiotherapy and image guidance. The combination of cobalt-60 (Co
      60) with 0.35 Tesla magnetic resonance imaging (MRI) allows for magnetic
      resonance (MR)-guided intensity-modulated radiation therapy (IMRT) delivery with
      multiple beams. This study investigated head and neck, lung, and prostate
      treatment plans to understand what is possible on ViewRay to narrow focus toward
      sites with optimal dosimetry. The goal is not to provide a rigorous assessment of
      planning capabilities, but rather a first order demonstration of ViewRay planning
      abilities. Images, structure sets, points, and dose from treatment plans created
      in Pinnacle for patients in our clinic were imported into ViewRay. The same
      objectives were used to assess plan quality and all critical structures were
      treated as similarly as possible. Homogeneity index (HI), conformity index (CI),
      and volume receiving <20% of prescription dose (DRx) were calculated to assess
      the plans. The 95% confidence intervals were recorded for all measurements and
      presented with the associated bars in graphs. The homogeneity index (D5/D95) had
      a 1-5% inhomogeneity increase for head and neck, 3-8% for lung, and 4-16% for
      prostate. CI revealed a modest conformity increase for lung. The volume receiving
      20% of the prescription dose increased 2-8% for head and neck and up to 4% for
      lung and prostate. Overall, for head and neck Co-60 ViewRay treatments planned
      with its Monte Carlo treatment planning software were comparable with 6 MV plans
      computed with convolution superposition algorithm on Pinnacle treatment planning
      system. 

PMID- 24872604
TI  - Monte Carlo study of MLC fields for cobalt therapy machine.
AB  - An automated Multi-Leaf Collimator (MLC) system has been developed as add-on for
      the cobalt-60 teletherapy machines available in India. The goal of the present
      computational study is to validate the MLC design using Monte Carlo (MC)
      modeling. The study was based on the Kirloskar-supplied Phoenix model machines
      that closely match the Atomic Energy of Canada Limited (AECL) theratron-80
      machine. The MLC is a retrofit attachment to the collimator assembly, with 14 non
      divergent leaf pairs of 40 mm thick, 7 mm wide, and 150 mm long tungsten alloy
      plates with rounded edges and 20 mm tongue and 2 mm groove in each leaf. In the
      present work, the source and collimator geometry has been investigated in detail
      to arrive at a model that best represents the measured dosimetric data. The
      authors have studied in detail the proto-I MLC built for cobalt-60. The MLC field
      sizes were MC simulated for 2 * 2 cm(2) to 14 * 14 cm(2) square fields as well as
      irregular fields, and the percent depth dose (PDD) and profile data were compared
      with ROPS(?) treatment planning system (TPS). In addition, measured profiles
      using the IMATRIXX system(?) were also compared with the MC simulations. The
      proto-I MLC can define radiation fields up to 14 * 14 cm(2) within 3 mm accuracy.
      The maximum measured leakage through the leaf ends in closed condition was 3.4%
      and interleaf leakage observed was 7.3%. Good agreement between MC results, ROPS
      and IMATRIXX results has been observed. The investigation also supports the
      hypothesis that optical and radiation field coincidence exists for the square
      fields studied with the MLC. Plots of the percent depth dose (PDD) data and
      profile data for clinically significant irregular fields have also been
      presented. The MC model was also investigated to speed up the calculations to
      allow calculations of clinically relevant conformal beams. (?)Radiation Oncology
      Planning System (ROPS) is supplied by Tirumala Jyothi Computer Systems described
      at https://sites.google.com/site/tjcsrops/ (?)IMATRIXX is supplied by IBA
      Dosimetry described at HYPERLINK http://www.iba-dosimetry.com. 

PMID- 24872605
TI  - Estimation of distance error by fuzzy set theory required for strength
      determination of HDR (192)Ir brachytherapy sources.
AB  - Verification of the strength of high dose rate (HDR) (192)Ir brachytherapy
      sources on receipt from the vendor is an important component of institutional
      quality assurance program. Either reference air-kerma rate (RAKR) or air-kerma
      strength (AKS) is the recommended quantity to specify the strength of gamma
      emitting brachytherapy sources. The use of Farmer-type cylindrical ionization
      chamber of sensitive volume 0.6 cm(3) is one of the recommended methods for
      measuring RAKR of HDR (192)Ir brachytherapy sources. While using the cylindrical
      chamber method, it is required to determine the positioning error of the
      ionization chamber with respect to the source which is called the distance error.
      An attempt has been made to apply the fuzzy set theory to estimate the subjective
      uncertainty associated with the distance error. A simplified approach of applying
      this fuzzy set theory has been proposed in the quantification of uncertainty
      associated with the distance error. In order to express the uncertainty in the
      framework of fuzzy sets, the uncertainty index was estimated and was found to be
      within 2.5%, which further indicates that the possibility of error in measuring
      such distance may be of this order. It is observed that the relative distance li
      estimated by analytical method and fuzzy set theoretic approach are consistent
      with each other. The crisp values of li estimated using analytical method lie
      within the bounds computed using fuzzy set theory. This indicates that li values
      estimated using analytical methods are within 2.5% uncertainty. This value of
      uncertainty in distance measurement should be incorporated in the uncertainty
      budget, while estimating the expanded uncertainty in HDR (192)Ir source strength
      measurement. 

PMID- 24872606
TI  - Investigation of the bystander effect in MRC5 cells after acute and fractionated
      irradiation in vitro.
AB  - Radiation-induced bystander effect (RIBE) has been defined as radiation responses
      observed in nonirradiated cells. It has been the focus of investigators worldwide
      due to the deleterious effects it induces in nonirradiated cells. The present
      study was performed to investigate whether acute or fractionated irradiation will
      evoke a differential bystander response in MRC5 cells. A normal human cell line
      (MRC5), and a human lung tumor cell line (QU-DB) were exposed to 0, 1, 2, and 4Gy
      of single acute or fractionated irradiation of equal fractions with a gap of 6 h.
      The MRC5 cells were supplemented with the media of irradiated cells and their
      micronucleus frequency was determined. The micronucleus frequency after single
      and fractionated irradiation did not vary significantly in the MRC5 cells
      conditioned with autologous or QU-DB cell-irradiated media, except for 4Gy where
      the frequency of micronucleated cells was lower in those MRC5 cells cultured in
      the media of QU-DB-exposed with a single dose of 4Gy. Our study demonstrates that
      the radiation-induced bystander effect was almost similar after single acute and
      fractionated exposure in MRC5 cells. 

PMID- 24872607
TI  - Potential of thermal imaging as a tool for prediction of cardiovascular disease.
AB  - Vascular dysfunction is associated with onset of cardiovascular disease (CVD).
      Its effect is reflected as temperature change on the skin. The aim of this work
      was to test the potential of thermal imaging as cost effective screening tool for
      prediction of CVD. Thermal imaging of various parts of the subject (N = 80,
      male/female =44/36, aged 25-75 years) was done using noncontact infrared (IR)
      camera. In each subject, total cholesterol (TC; mg/dl) and high-density
      lipoprotein (HDL, mg/dl) were measured according to standard biochemical
      analysis. Based on National Cholesterol Education Program ATP III criteria,
      subject with known CVD (N = 16) and age- and sex- matched normal subjects (N =
      21) were included in the study. The average surface temperature of various parts
      from head to toe was calculated and statistical analysis was performed between
      the groups. In the total population (N = 37), correlation study shows TC (mg/dl)
      was correlated with measured surface temperature of the following regions:
      Temporal left (r = -0.316) and right (r = -0.417), neck left (r = 0.347) and
      right (r = -0.410), and hand left (r = 0.387). HDL (mg/dl) was found to be
      correlated with measured surface temperature of the following regions: Temporal
      left (r = 0.445) and right (r = 0.458), hand left (r = -0.470), and foot anterior
      left (r = -0.332) and right (r = -0.336). Temperature asymmetry was more
      significant in upper extremity in CVD group. Using the surface temperature,
      regression models were calculated for noninvasive estimation of TC and HDL. The
      predictive ability of measured surface temperature for TC and HDL was 60%. The
      model for noninvasive estimation gave sensitivity and specificity value of 79 and
      83% for TC and 78 and 81% for HDL, respectively. Thus, the surface temperature
      can be one of the screening tools for prediction of CVD. The limitation of the
      present study is also discussed under future work. 

PMID- 24872608
TI  - Assessments of natural radioactivity and determination of heavy metals in soil
      around industrial dumpsites in Sango-Ota, Ogun state, Nigeria.
AB  - The activity concentration of natural radionuclides in soil samples from
      industrial dumpsites in Sango-Ota were determined using gamma-ray spectrometry
      with NaI(Tl) detector. The mean activity concentration of (226)Ra, (232)Th and
      (40)K was 3.0 +/- 1.2, 33.3 +/- 9.8 and 122.1 +/- 20.6 Bqkg(-1), respectively.
      Radium equivalent activities were calculated to assess the hazards arising from
      the use of the soil sample in agriculture. All the calculated values were lower
      than the world average. The mean concentration of heavy metals in the soil
      samples were 33.6, 2.9, 3.8, 2.7, 48.9, 1,5, 34.5 and 0.8 mg l(-1) for Cu, Mg,
      Ca, P, Fe, Pb, Zn and Cd, respectively. The concentrations of Cd, Cu and Pb were
      higher than the natural permissible range in soil. Therefore, the government
      should discourage the use of the soil around dumpsites for planting because of
      the presence of heavy metals in the sites. 

PMID- 24872609
TI  - A study of photon interaction parameters in lung tissue substitutes.
AB  - The study of photon interaction with different composite materials has become a
      topic of prime importance for radiation physicists. Some parameters of dosimetric
      interest are the mass attenuation coefficient, effective atomic number, and
      electron density; these help in the basic understanding of photon interactions
      with composite materials. The photon interaction parameters such as mass
      attenuation coefficient (MU/rho), effective atomic number (Zeff), and effective
      electron density (N el) must be identical for the phantom material and their
      tissue. In the present study, we have evaluated the photon interaction parameters
      such as (MU/rho), Z eff and N el of 13 lung tissue substitutes. The variations of
      these parameters of lung tissue substitutes with photon energy are graphically
      represented. The photon interaction parameters of lung tissue substitutes are
      compared with that of lung tissue. The variation of photon interaction parameters
      of the studied lung tissue substitutes is similar that of the lung. Logically, it
      can be shown that Alderson lung is good substitute for lung than the other
      substitutes. 

PMID- 24872610
TI  - Implementation of a program for quality assurance on leaf positioning accuracy
      using Gafchromic((r)) RTQA2 films.
AB  - In radiotherapy treatments the correct dose delivery to the target volume and the
      consequent conservation of healthy tissues is affected by multileaf collimator
      (MLC) leaf positioning accuracy and reproducibility, mostly in intensity
      modulated radiation therapy (IMRT): For this reason a quality assurance (QA)
      program is necessary to ensure the best treatment possible to each patient. The
      aim of this study is the implementation of a method using Gafchromic((r)) RTQA 2
      films to perform routine QA on the MLC, both for qualitative and quantitative
      analysis. A flatbed document scanner (Epson 10000XL) was used in conjunction with
      radiochromic detector; a scanning protocol was firstly defined to improve readout
      accuracy. RTQA2 films were irradiated with 6 MV X-rays at different dose levels
      to obtain calibration curve. To evaluate the leaf positioning accuracy in
      different conditions, a rhomboidal shape and a field consisting in three
      rectangular segments were selected. The images quantitative analysis was handled
      with a program developed in MATLAB to evaluate the differences between expected
      and measured leaves positions. The reproducibility and global uncertainty of the
      method were estimated to be equal to 0.5% and 0.6 mm, respectively. Moreover, a
      qualitative test was performed: A garden picket fence field, consisting in
      multiple segments 2 * 22 cm(2), was realized setting known leaves shifts to test
      the method sensitivity. The picket fence test shows that the method is able to
      detect displacements equal to 1 mm. The results suggest that Gafchromic((r))
      RTQA2 films represent a reliable tool to perform MLC routine QA. 

PMID- 24872612
TI  - Life after death by power point: PechaKucha to the rescue?

PMID- 24872611
TI  - Comparative analysis of volumetric-modulated arc therapy and intensity-modulated
      radiotherapy for base of tongue cancer.
AB  - The aim of this study was to compare the various dosimetric parameters of dynamic
      multileaf collimator (MLC) intensity modulated radiation therapy (IMRT) plans
      with volumetric modulated arc therapy (VMAT) plans for base of tongue cases. All
      plans were done in Monaco planning system for Elekta synergy linear accelerator
      with 80 MLC. IMRT plans were planned with nine stationary beams, and VMAT plans
      were done for 360 degrees  arc with single arc or dual arc. The dose to the
      planning target volumes (PTV) for 70, 63, and 56 Gy was compared. The dose to 95,
      98, and 50% volume of PTV were analyzed. The homogeneity index (HI) and the
      conformity index (CI) of the PTV70 were also analyzed. IMRT and VMAT plan showed
      similar dose coverage, HI, and CI. Maximum dose and dose to 1-cc volume of spinal
      cord, planning risk volume (PRV) cord, and brain stem were compared. IMRT plan
      and VMAT plan showed similar results except for the 1 cc of PRV cord that
      received slightly higher dose in VMAT plan. Mean dose and dose to 50% volume of
      right and left parotid glands were analyzed. VMAT plan gave better sparing of
      parotid glands than IMRT. In normal tissue dose analyses VMAT was better than
      IMRT. The number of monitor units (MU) required for delivering the good quality
      of the plan and the time required to deliver the plan for IMRT and VMAT were
      compared. The number of MUs for VMAT was higher than that of IMRT plans. However,
      the delivery time was reduced by a factor of two for VMAT compared with IMRT.
      VMAT plans yielded good quality of the plan compared with IMRT, resulting in
      reduced treatment time and improved efficiency for base of tongue cases. 

PMID- 24872613
TI  - Conference: A place for scientific appetite or gourmet feast.

PMID- 24872614
TI  - Take off!!!!

PMID- 24872615
TI  - Acute gingival bleeding and falciparum malaria.

PMID- 24872616
TI  - Role of Triphala in dentistry.
AB  - Ayurveda is considered as the "science of life," because the ancient Indian
      system of health care focused views of man and his illness. India has an age-old
      heritage of traditional herbal medicine. Conventional drugs usually provide
      effective antibiotic therapy for bacterial infections, but there is an increasing
      problem of antibiotic resistance and a continuing need for new solutions. Hence,
      now herbal drugs are being preferred to synthetic antibiotics. 'Triphala' is a
      well-known powdered preparation in the Indian system of medicine (ISM). It
      consists of equal parts of the Emblica officinalis, Terminalia chebula, and
      Terminalia belerica. Currently, Triphala is being extensively researched for its
      various therapeutic effects including its anti-caries, antioxidant, anti
      collagenase, and anti-microbial activities. The present review will focus on the
      comprehensive appraisal of Triphala and its several applications in dentistry. 

PMID- 24872617
TI  - Exploring the role of cranberry polyphenols in periodontits: A brief review.
AB  - Cranberry juice polyphenols have gained importance over the past decade due to
      their promising health benefits. The bioactive component, proanthocyanidins is
      mainly responsible for its protective effect. A lot has been said about its role
      in urinary tract infection and other systemic diseases, but little is known about
      its oral benefits. An extensive search was carried out in the PubMed database
      using the terms "cranberry polyphenols" and "periodontitis" together. The
      institute library was also thoroughly scrutinized for all relevant information.
      Thus, a paper was formulated, the aim of which was to review the role of high
      molecular weight cranberry fraction on oral tissues and periodontal diseases. 

PMID- 24872618
TI  - Comparative evaluation of plasma ROM levels in chronic periodontitis patients
      before and after non-surgical and surgical periodontal therapy: A clinical trial.
AB  - OBJECTIVE: Chronic periodontitis (CP) is associated with increased levels of
      blood reactive oxygen species (ROS). So, treatment of CP may lead to decrease in
      blood ROS. However, not much literature is available comparing the effect of
      surgical and non-surgical periodontal treatment on blood ROS levels. Reactive
      oxygen metabolites (ROMs) are a useful measure of blood ROS. The aim of this
      study was to investigate the effect of periodontal treatment on plasma ROM levels
      in CP patients. MATERIALS AND METHODS: Thirty CP patients and 15 controls were
      monitored. Plasma samples were collected at baseline and the clinical parameters
      were recorded. The CP patients were randomly divided into two groups: Scaling and
      root planing (Group II) and periodontal flap surgery (Group III). Both groups
      were re-evaluated 1 and 2 months after therapy. Clinical parameters were
      reviewed, plasma samples collected, and ROM levels were determined using a
      spectrophotometric technique. RESULTS: At baseline, the ROM levels for Group II
      and Group III were 519.8 +/- 62.4 and 513.4 +/- 74.7 CARR U, respectively, which
      were higher than Group I value (282.9 +/- 23.9, P < 0.001). Periodontal treatment
      in CP patients resulted in improvement of clinical parameters and a highly
      significant reduction in plasma ROM level (P < 0.001) after 2 months. Also, there
      was a more significant reduction in plasma ROM levels in Group III as compared to
      Group II (P < 0.05). CONCLUSIONS: In CP patients, surgical periodontal treatment
      was more effective in lowering the plasma ROM levels than when non-surgical
      periodontal treatment was performed alone and, therefore, may be more beneficial
      in reducing systemic oxidative stress.

PMID- 24872619
TI  - Histopathologic and histomorphometric studies and determination of IL-8 in
      patients with periodontal disease.
AB  - BACKGROUND: Periodontitis is an inflammatory disease characterized by connective
      tissue breakdown and alveolar bone resorption. OBJECTIVE: The aim of this study
      was to make a quantitative evaluation of the gingival tissue components in
      biopsies from patients with different clinical states of periodontal disease and
      to determine the relationship between the presence of interleukin-8 and the
      tissue destruction. MATERIALS AND METHODS: The study group consisted of 33
      biopsies from adult subjects. A total of 25 periodontal patients were sub
      classified on the basis of the clinical and radiographic criteria in mild,
      moderate and advanced periodontitis. Gingival samples were obtained from patients
      in the course of basic periodontal surgeries as a muco-periostic collate. Data
      were analyzed by the SPSS system. RESULTS: Collagen fibres decreased as non
      specific chronic states increased. A lymphocyte inflammatory infiltrate changed
      to a lymphoplasmocytary form. Reactivity to interleukin-8 was detected with the
      severity of the histopathologic diagnoses; however there was no association with
      the clinical diagnoses. CONCLUSIONS: Histopathology and histomorphometry of
      gingival tissue changed with the degree of inflammation. No evidence of
      interleukin-8 as a biomarker for clinical diagnoses of periodontitis was
      obtained.

PMID- 24872620
TI  - mRNA expression of pattern recognition receptors and their signaling mediators in
      healthy and diseased gingival tissues.
AB  - BACKGROUND: Gingivitis and periodontitis are initiated by inflammation caused by
      microorganisms. Pathogen-associated molecular patterns (PAMPs) from these
      microorganisms are recognized through various toll-like receptors (TLRs) and NOD
      like receptors (NLRs). In this study, we have chosen five TLRs and two NLRs as
      representatives taking part in the recognition and inflammation process, along
      with a few of their signaling mediators including CD14, MYD88, and TRIF to
      compare their mRNA expression levels between healthy and diseased gingival
      tissues. This will provide deeper insight into the mechanisms underlying
      gingivitis and periodontitis. Understanding the mechanisms involved in the onset
      and progression of the periodontal diseases could greatly help in establishing
      effective ways for prevention and treatment of these diseases besides decreasing
      the risk factor for relevant systemic disorders. MATERIALS AND METHODS: Gingival
      tissue samples for mRNA extraction and cDNA synthesis were taken from patients
      with gingivitis and periodontitis and from healthy control subjects. Messenger
      RNA expression of all genes was assessed using real-time polymerase chain
      reaction (PCR). RESULTS: Among the genes studied in different groups, only MYD88
      mRNA expression was significantly higher in the periodontitis group compared to
      that of the controls. The expression level of this molecule was also
      significantly higher in patients with severe periodontitis compared to other
      patients and also compared to healthy individuals. In different tissues, positive
      significant correlations were observed between the mRNA expression levels of some
      genes. CONCLUSIONS: Elevated mRNA levels of MYD88 in periodontitis might have a
      key role in the pathogenesis of this disease. Therefore, MYD88 may be a useful
      target for the therapy of this disease.

PMID- 24872621
TI  - Comparison of culture and polymerase chain reaction techniques in the
      identification of Tannerella forsythia in periodontal health and disease, an in
      vitro study.
AB  - BACKGROUND AND OBJECTIVES: Various bacterial species from subgingival biofilm
      have demonstrated aetiological relevance in the initiation and progression of
      periodontitis. The aim of this study was to detect the presence of Tannerella
      forsythia (Tf) in subgingival plaque of periodontally healthy subjects and
      chronic periodontitis patients by using both culture and PCR technique and
      compare the two techniques. MATERIALS AND METHODS: Pooled subgingival plaque
      samples were taken using sterile curettes from predetermined sites in 50
      periodontally healthy subjects and from 50 periodontitis subjects. Samples were
      analyzed for the presence of T. forsythia using both techniques. Statistical
      analysis of the results was done using Chi-square test, sensitivity, and
      specificity tests. RESULTS: Both techniques could detect T. forsythia in
      subgingival plaque samples from healthy and periodontitis subjects. Periodontally
      healthy individuals and individuals with chronic periodontitis using the culture
      technique showed the presence of T. forsythia in 14 and 34%, respectively. PCR
      technique showed the presence of T. forsythia in 20% healthy and 40% chronic
      periodontitis patients. T. forsythia detection in the periodontitis group was
      statistically significantly higher when compared to the healthy group by both
      culture and PCR technique (P = 0.019 and P = 0.029). PCR demonstrated high
      sensitivity and low specificity when compared to the culture technique.
      CONCLUSION: The results indicated that T. forsythia was more prevalent in
      periodontitis patients when compared with healthy subjects. The PCR was found to
      be more sensitive than culture technique for detection of T. forsythia from the
      subgingival plaque samples.

PMID- 24872622
TI  - Immunolocalization of Ki-67 in different periodontal conditions.
AB  - BACKGROUND: Ki-67 which is a non-histone nuclear protein which is expressed in
      proliferating cells, during all the active phases of the cell cycle. Increased Ki
      67 expression has been seen in several inflammatory and malignant conditions like
      diabetes, rheumatoid arthritis, atherosclerosis, pancreatitis and squamous cell
      carcinoma. AIM: The aim of the present study is to analyze the expression of Ki
      67 in gingival tissues by immunohistochemistry in smokers and non-smokers with
      healthy gingiva and chronic periodontitis. MATERIALS AND METHODS: Gingival
      biopsies (n = 32) were obtained from smokers who had clinically healthy gingiva
      (n = 8), smokers with periodontitis (n = 8), chronic periodontitis (n = 8) and
      healthy gingiva (n = 8). The expression of Ki-67 was evaluated
      immunohistochemically. STATISTICAL ANALYSIS USED: Mean and standard deviation
      were estimated for the gingival tissue extract sample for each study group. Mean
      values were compared between different study groups by, one way ANOVA, post hoc
      analysis. In this study P < 0.05 was considered as the level of significance.
      RESULTS: The mean number of Ki-67 positive cells/field was higher in the smokers
      with periodontitis group. When the mean Ki-67 positive cells were compared
      between different groups, statistical significant difference was observed between
      healthy and both the periodontitis groups (P = 0.000) and between smokers group
      (P = 0.001). CONCLUSIONS: Ki-67 was maximally expressed in smoker with
      periodontitis followed by chronic periodontitis patients, healthy smokers and
      healthy control patients which shed light on the toxic effects of tobacco in
      dysregulating the cell cycle and cellular proliferation. The findings of this
      study also help us to understand the role of the cell cycle in resolution of
      periodontal inflammation which is a salient feature in the pathogenesis of
      chronic periodontitis.

PMID- 24872624
TI  - Comparative evaluation of subgingivally delivered xanthan-based chlorhexidine gel
      and herbal extract gel in the treatment of chronic periodontitis.
AB  - BACKGROUND: Local drug delivery agents can effectively deliver the antimicrobial
      drugs in bactericidal concentration, and have shown improved clinical outcomes
      when used as an adjunct to mechanical therapy. The aim of this study was to
      evaluate the efficacy of a xanthan-based chlorhexidine gel versus herbal
      extracts' gel as an adjunct to periodontal therapy in the treatment of chronic
      periodontitis. MATERIALS AND METHODS: A total of 150 sites, age group of 30-50
      years, periodontal pockets measuring 5-8 mm and diagnosed with chronic
      periodontitis were selected for the study. The selected sites were randomized in
      five groups: Scaling and root planing (SRP) alone (Group A), SRP + Chlosite gel
      (Group B), SRP + Herbal gel (Group C), Chlosite gel alone (Group D) and Herbal
      gel alone (Group E). Clinical parameters such as Plaque Index, Gingival Index,
      probing pocket depth and clinical attachment level were recorded at baseline and
      1- and 3-month intervals. RESULTS: After 3 months, there were statistically
      significant reductions in all the clinical parameters for Groups B and C compared
      with Group A. There was no significant reduction in all clinical parameters
      between Group D and E where no mechanical therapy was performed. CONCLUSION: The
      results indicate that the local application of herbal gel can be comparably used
      as chlorhexidine gel in the treatment of chronic periodontitis as an adjunct to
      mechanical periodontal therapy.

PMID- 24872623
TI  - Aggressive periodontitis: A clinico-hematological appraisal.
AB  - BACKGROUND: Human leukocyte antigens (HLA) have been considered a candidate of
      genetic risk markers for aggressive periodontitis (AP). AP has also been
      associated with polymorphonuclear leukocyte (PMN) dysfunction. The role of
      monocyte subsets in AP has also not been completely explored. Therefore, the
      present study was undertaken to assess in, AP subjects, the possible association
      between defective PMN adhesion and beta2-integrin expression; defective
      neutrophil migration and actin polymerization level; the expression of ABO blood
      group and HLA antigen; and the percentage of CD14+ CD16+ monocytes and CD45RA
      monocytes. All these parameters have been compared with the subjects of chronic
      periodontitis (CP) and healthy controls. MATERIALS AND METHODS: A total of 45
      subjects of the age group 20-50 years, free from any known systemic disease, were
      divided into three groups - Group I - periodontally healthy control (n = 15),
      Group II - CP (n = 15) and Group III - AP (n = 15). Peripheral blood samples were
      collected. ABO grouping and HLA typing were performed. beta2-integrin expression,
      actin polymerization level and percentage of CD14+ CD16+ monocytes and CD45RA
      monocytes were estimated by fluorescence-activated cell sorter analysis. RESULTS:
      Most of the subjects of AP belonged to the blood group AB, and an increased
      frequency of HLA-A30, CW1 and DR1 (P < 0.1) and B44 and DQ2 (P < 0.05) were also
      observed in this group. In the AP group, both average values (beta2-integrin and
      actin level) were significantly less than those of normal subjects (P < 0.001).
      The mean percentage of CD14+ CD16+ monocytes was found to be maximum in CP,
      followed by AP, and then in healthy subjects, while the mean percentage of CD45RA
      was maximum in AP, followed by CP, and then in healthy subjects. CONCLUSIONS:
      With the present state of knowledge from this study, a definite association of
      ABO blood groups and HLA phenotypes with periodontal diseases is yet to be
      established. Leukocytic functional defects were found in AP subjects. A
      statistically significant percentage of CD14+ CD16+ and CD45RA monocytes were
      found in AP subjects as compared with the normal control and CP groups.

PMID- 24872625
TI  - Comparative evaluation of the antiplaque effectiveness of green tea catechin
      mouthwash with chlorhexidine gluconate.
AB  - AIM: The aim of this study is to compare the antiplaque efficacy of green tea
      catechin mouthwash with chlorhexidine gluconate mouthwash. MATERIALS AND METHODS:
      A single blinded cross-over study was conducted among 30 participants in the age
      group of 18-25 years. The mouthwash samples for the study were previously labeled
      assigning the letters: A (0.25% of green tea catechin mouthwash) and B (0.12% of
      chlorhexidine mouthwash). The study subjects were randomly divided into two
      groups of 15 each and the study was divided into two phases. In phase I, the
      mouthwash A was given to one group and other group was given mouthwash B. After a
      15 day washout period, in phase II, both groups were given other mouthwash. At
      the end of each phase of 1 week, plaque score was recorded by using Turesky
      modification of the Quigley-Hein plaque index. RESULTS: The plaque scores were
      compared and the difference between the green tea catechin and chlorhexidine
      mouthwash was determined by t-test. The difference between plaque scores were not
      statistically significant (P > 0.05). The results showed that both the groups
      that is green tea catechin mouthwash (0.25%) and chlorhexidine mouthwash (0.12%)
      have comparable results in plaque reduction. CONCLUSION: This study supports the
      effectiveness of green tea catechin mouthwash as an antiplaque agent. It should
      be explored as a cost-effective, long-term antiplaque rinse with prophylactic
      benefits.

PMID- 24872626
TI  - Assessment and comparison of anemia of chronic disease in healthy subjects and
      chronic periodontitis patients: A clinical and hematological study.
AB  - BACKGROUND: Bacteremia is associated with periodontal diseases whose extent is
      related to the severity of inflammation in periodontal tissues. The purpose of
      this study was to assess and compare the various blood parameters in healthy
      subjects and severe chronic periodontitis patients. MATERIALS AND METHODS: 100
      patients with severe chronic periodontitis (test group) and 100 periodontally
      healthy subjects (control group) in the age group 35-60 years participated in the
      study. Blood parameters were recorded with blood samples drawn from the
      antecubital fossa by venous puncture. RESULTS: Periodontitis group showed lower
      erythrocyte count and mean corpuscular hemoglobin concentration (MCHC), and
      increased total leukocyte count (TLC) and neutrophil, lymphocyte, and eosinophil
      count, compared to the healthy control group. CONCLUSIONS: To conclude,
      periodontitis may tend toward anemia and there is marked leukocytosis due to
      increased number of circulating neutrophils and lymphocytes.

PMID- 24872627
TI  - Serum zinc and magnesium concentrations in type 2 diabetes mellitus with
      periodontitis.
AB  - AIM: The purpose of the study was to evaluate the serum levels of zinc (Zn) and
      magnesium (Mg) in type 2 diabetes mellitus (DM) with periodontitis patients and
      to correlate them with the levels of serum cholesterol, high density lipoprotein
      cholesterol (HDL-c), low density lipoprotein cholesterol (LDL-c), and
      triglycerides among the study subjects. MATERIALS AND METHODS: A total of 600
      subjects participated in the study, who were divided into four groups as control
      healthy individuals (group I), type 2 DM without periodontitis (group II), type 2
      DM with periodontitis (group III), and periodontitis subjects without DM (group
      IV), matched for age, sex, and duration of diabetes. Serum concentrations of
      glucose, total cholesterol, triglycerides, HDL-c, Zn, and Mg were measured using
      enzymatic methods in an UV absorption spectrophotometer, and LDL-c was calculated
      using Friedwald's formula. Student's t-test, Pearson correlations, and analysis
      of variance (ANOVA) tests were used for statistical analysis. RESULTS: The serum
      zinc level was found to be significantly increased in type 2 DM without
      periodontitis (group II) and periodontitis subjects without type 2 DM (group IV)
      (P < 0.0001), and the level was lowered in type 2 DM with periodontitis (group
      III) when compared to control. The serum Mg level was found to be significantly
      decreased (P < 0.0001) in group II, group III, and in group IV, when compared to
      control. We found a significant increased level of serum total cholesterol and
      LDL-c and decreased triglycerides and HDL-c in type 2 DM subjects with
      periodontitis (group III, P < 0.0001). CONCLUSION: Patients with DM and
      periodontitis had altered metabolism of Zn and Mg which were linked to increased
      values of serum cholesterol and LDL-c and decreased HDL-c, contributing to the
      progression and complications of type 2 DM with periodontitis.

PMID- 24872628
TI  - Embrasure morphology and central papilla recession.
AB  - BACKGROUND: The aim of this study was to ascertain the effects of vertical and
      horizontal distances between the maxillary central incisors on the presence of
      interproximal dental papilla and to assess the association between the embrasure
      morphology and central papilla recession. MATERIALS AND METHODS: The central
      papilla was visually assessed in 50 subjects using the standardized periapical
      radiographs of maxillary central incisors. The following vertical distances were
      measured; distance from the contact point to papilla tip, CP to proximal
      cementoenamel (pCEJ) junction, bone crest to CP (BC-CP) and BC-PT. The horizontal
      distance measured was interdental width (IDW) at pCEJ level. The measurements
      were recorded using a digital electronic caliper. RESULTS: Significant
      association between the embrasure morphology and central papilla recession was
      observed for all study groups. All the interdental variables were significantly
      related to the presence of interdental papillae, with BC-CP distance being the
      strongest determinant of central papilla presence. The percentage of interdental
      papilla presence was 100% when the BC-CP distance was <=6 mm and IDW ranged
      between 0.5 and 1.5 mm. Central papilla recession was observed most frequently
      with wide-long and narrow-long embrasure morphology. CONCLUSION: In relation to
      maxillary central incisors, all the interdental variables have significant
      influences on the presence of interdental papillae, with distance from BC to CP
      being the strongest determinant of central papilla presence.

PMID- 24872629
TI  - Orthodontic management of dentition in patients with periodontally compromised
      dentition.
AB  - BACKGROUND: An increasing number of adult patients are seeking orthodontic
      treatment to improve their dental appearance. However, special attention must be
      given to the periodontal status of the adults as periodontal disease and its
      sequel, such as pathologic migration of anterior teeth, result in esthetic and
      functional problems. In such adult patients, an interdisciplinary approach often
      offers the best option for achieving a predictable outcome to solve complex
      clinical problems. MATERIALS AND METHODS: A prospective study was carried out on
      20 adult patients [mean age = 33.3 +/- 4.52 (SD), 11 females and nine males] with
      periodontally compromised and malaligned dentition. Loe and Silness Gingival
      Index (GI), Ramfjord's Periodontal Disease Index (PDI) and Dental Aesthetic Index
      (DAI) were recorded at the start and after completion of treatment. RESULTS:
      Comparison of GI, PDI and DAI before and after completion of treatment showed
      statistically significant differences, indicating the relevance of combined
      orthodontic-periodontic treatment in periodontally compromised dentition (P <
      0.01). CONCLUSION: The outcome of the study showed that an interdisciplinary
      approach is a simple solution for complex clinical problems arising as a sequel
      to periodontitis, such as pathological tooth migration, restoring function,
      esthetics and periodontal health.

PMID- 24872630
TI  - Evaluation of the role of antibiotics in preventing postoperative complication
      after routine periodontal surgery: A comparative clinical study.
AB  - BACKGROUND AND OBJECTIVES: Aim of this randomly controlled clinical study was to
      evaluate the role of antibiotics to prevent postoperative complications after
      routine periodontal surgery and also to determine whether their administration
      improved the surgical outcome. MATERIALS AND METHODS: Forty-five systemically
      healthy patients with moderate to severe chronic periodontitis requiring flap
      surgery were enrolled in the study. They were randomly allocated to Amoxicillin,
      Doxycycline, and control groups. Surgical procedures were carried out with
      complete asepsis as per the protocol. Postoperative assessment of patient
      variables like swelling, pain, temperature, infection, ulceration, necrosis, and
      trismus was performed at intervals of 24 h, 48 h, 1 week, and 3 months. Changes
      in clinical parameters such as gingival index, plaque index, probing pocket
      depth, and clinical attachment level were also recorded. RESULTS: There was no
      incidence of postoperative infection in any of the patients. Patient variables
      were comparable in all the three groups. Though there was significant improvement
      in the periodontal parameters in all the groups, no statistically significant
      result was observed for any group over the others. CONCLUSION: Results of this
      study showed that when periodontal surgical procedures were performed following
      strict asepsis, the incidence of clinical infection was not significant among all
      the three groups, and also that antibiotic administration did not influence the
      outcome of surgery. Therefore, prophylactic antibiotics for patients who are
      otherwise healthy administered following routine periodontal surgery to prevent
      postoperative infection are unnecessary and have no demonstrable additional
      benefits.

PMID- 24872632
TI  - Interleukin-1beta level in peri-implant crevicular fluid and its correlation with
      the clinical and radiographic parameters.
AB  - BACKGROUND AND OBJECTIVES: Assessing only the clinical and radiographic
      parameters for evaluation of dental implants may not be enough as they often
      reflect extensive inflammatory changes in the periodontal tissues. As peri
      implant crevicular fluid (PICF) can give us a more prompt and objective measure
      of the disease activity, the purpose of this case series is to assess the peri
      implant health status of single tooth dental implants not only clinically and
      radiographically but also biochemically. MATERIALS AND METHODS: Thirteen patients
      were subjected to dental implants at single edentulous sites using a conventional
      surgical approach. At baseline, 6 months, and 12 months after implant placement,
      the clinical and radiographic parameters were recorded. Additionally, IL-1beta in
      PICF was estimated using the ELISA kit at 6(th) and 12(th) month. RESULTS: The
      clinical and radiographic parameters differed significantly around the implants
      at different time intervals with IL-1beta levels showing highly significant
      differences between 6 months (31.79 +/- 12.26 pg/MUl) and 12 months (113.09 +/-
      51.11 pg/MUl). However, Spearman's correlation coefficient showed no correlation
      with the clinical and radiographic parameters. INTERPRETATION AND CONCLUSION:
      Assessment of the various parameters confirmed that all the implants had a
      healthy peri-implant status. Although the levels of IL-1beta in PICF were
      elevated at the 12(th) month, they were well within the healthy range as observed
      by previous studies. This indicates that IL-1beta, a biochemical marker, can be
      used as an adjunct to clinical and radiographic parameters in the assessment of
      EARLY inflammatory changes around implants.

PMID- 24872631
TI  - Comparison of nanocrystalline hydroxyapatite and synthetic resorbable
      hydroxyapatite graft in the treatment of intrabony defects: A clinical and
      radiographic study.
AB  - BACKGROUND: The aim of this study is to compare, clinically and radiographically,
      the effectiveness of nanocrystalline hydroxyapatite (NHA) and synthetic
      resorbable hydroxyapatite (HA) in the treatment of intrabony defects. MATERIALS
      AND METHODS: Ten subjects with bilateral defects, with probing depth (PD) 6-9 mm
      and radiographic evidence of an intraosseous component >=4 mm participated in the
      present study. Subjects were allocated randomly to treatment with NHA (test
      group) or HA (control group). At baseline, 3 and 6 months after surgery, the
      following clinical parameters were recorded: Plaque index, gingival index, PD,
      relative attachment level (RAL), and radiographic reduction in intrabony defect.
      RESULTS: At 6 months following therapy, the test group showed a reduction in mean
      PD from 6.4 +/- 0.843 to 3.3 +/- 0.8232 mm and a change in mean RAL from 12.9 +/-
      1.197 to 10.1 +/- 0.7378 mm, whereas in the control group the mean PD decreased
      from 7.65 +/- 1.8566 to 3.9 +/- 1.1005 mm, and mean RAL decreased from 13.9 +/-
      0.9944 to 10.7 +/- 0.6749 mm. On comparison of the mean difference in probing
      depth between the two groups after the unpaired t-test was applied at baseline, 3
      months and 6 months, scores were found to be statistically non-significant (P >
      0.01). CONCLUSION: The results of the present study indicate that both NHA and
      conventional HA led to the improvement of clinical and radiographic parameters
      over the course of the study. However, the test group did not show any
      significant improvement over the control group.

PMID- 24872634
TI  - Periodontal considerations in a patient with glucose-6-phosphate dehydrogenase
      deficiency with associated pancytopenia: A rare case report.
AB  - Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzyme
      defect in humans. G6PD deficiency is widely distributed in tropical and
      subtropical parts of the world and a conservative estimate is that at least 500
      million people have a G6PD deficient gene. In several of these areas, the
      frequency of a G6PD deficiency gene may be as high as 20% or more. The vast
      majority of people with G6PD deficiency remain clinically asymptomatic throughout
      their lifetime. However, all of them have an increased risk of developing
      neonatal jaundice and a risk of developing acute hemolytic anemia when challenged
      by a number of oxidative agents. The most important treatment measure is
      prevention: Avoidance of the drugs and foods that cause hemolysis. 

PMID- 24872633
TI  - Incidence of amlodipine-induced gingival overgrowth in the rural population of
      Loni.
AB  - AIMS: Since the incidence of gingival overgrowth induced by amlodipine remains
      poorly defined, this study was carried out with an aim to determine the
      incidence. MATERIALS AND METHODS: Dental patients who received amlodipine (N =
      115), for more than 3 months were studied to determine the drug-induced gingival
      overgrowth. Clinical diagnosis of drug-induced overgrowth was verified by
      disappearance or decreased severity of gingival overgrowth after withdrawal of
      the causative drug. RESULTS: The prevalence rate of amlodipine-induced gingival
      hyperplasia among experimental patients was 3.4%, while it was not observed among
      the control subjects. Oral examination revealed gingival overgrowth as a lobular
      or nodular enlargement on interdental papilla located in the anterior
      interproximal regions. CONCLUSIONS: In this study, there was a significant
      relationship between gingival inflammation resulting from dental plaque and drug
      dosage, and hyperplasia.

PMID- 24872635
TI  - Juvenile trabecular ossifying fibroma.
AB  - Juvenile ossifying fibroma (JOF) is an uncommon fibro-osseous lesion with highly
      aggressive clinical behavior, higher incidence in young adults, and a strong
      tendency to recur. Two categories, trabecular JOF (TrJOF) and psammomatoid JOF
      (PsJOF), based on histologic criteria and a distinct predilection for specific
      age groups have been identified. Juvenile trabecular ossifying fibroma of
      peripheral variety is an uncommon clinical entity with aggressive local behavior
      and high recurrence rate. This article reports a case of aggressive JTOF in the
      anterior mandibular region in a 13-year-old boy with history of recurrence.
      Complete surgical resection of the growth was done along with involved
      periodontal ligament and periosteum to minimize the possibility of recurrence.
      The case was followed up for more than 3 months without recurrence. 

PMID- 24872636
TI  - Pyogenic granuloma near the midline of the oral cavity: A series of case reports.
AB  - Pyogenic granuloma (PyG) is a common cause of swelling in the oral cavity during
      pregnancy and also as an exaggerated response to any minor trauma. The condition
      is frequently associated with periodontal pain and discomfort, in some cases
      interfering with mastication and creating esthetic problems. Six patients
      reported to the Department of Periodontics with gingival overgrowth in the lower
      anteriors. After recording the details of the patients' oral hygiene status, all
      the patients were provided initial therapy with scaling and were prescribed
      analgesics for the reduction of pain and discomfort. After 1 week, surgical
      excision of the overgrowth was performed and sent for histopathological analysis.
      The histopathological report is suggestive of PyG. 

PMID- 24872637
TI  - Central odontogenic fibroma.
AB  - Central odontogenic fibroma (COF), which has been categorized under the
      subheading of odontogenic tumors of ectomesenchyme, is such an uncommon neoplasm
      that much of its nature is left uncharted. COF is a rare tumor that accounts for
      0.1% of all odontogenic tumors. Clinically, the lesion grows slowly and leads to
      cortical expansion. Radiologically, the lesion may be unilocular or multilocular.
      In some cases, it may be associated with root resorption or displacement.
      Histopathologically, the lesion is characterized by mature collagen fibers and
      numerous fibroblasts. A case of COF of the mandible in a male patient aged 49
      years is described in this report. The patient showed no symptoms, no history of
      swelling discomfort or pain, and was unaware of the presence of the lesion.
      Orthopantomogram (OPG) showed generalized bone loss along with a unilocular
      radiolucent area, with a clear sclerotic lining and angular bone loss. Surgical
      enucleation of the lesion along with placement of osseo-graft, which is a
      bioresorbable demineralized bone matrix (DMBM), and platelet-rich fibrin was
      carried out in the defect site. Following surgery, patient was recalled for
      revaluation of the lesion; the surgical site showed good healing and an increase
      in bone height was seen. 

PMID- 24872638
TI  - Idiopathic gingival enlargement associated with generalized aggressive
      periodontitis in a 19-year-old female.
AB  - Gingival enlargement, one of the manifestations of gingival and periodontal
      disease, is also known as gingival overgrowth. Idiopathic gingival enlargement is
      a rare gingival overgrowth, which is of an undetermined cause. This unknown
      etiology has now been linked to specific genes and idiopathic gingival
      enlargement is at times referred to as hereditary gingival enlargement. This
      condition is a benign, slow growing proliferation of gingival tissues. Aggressive
      periodontitis is the rapid form of periodontal disease which is characterized by
      extensive periodontal tissue destruction, increased host-susceptibility toward
      periodontal disease progress and a genetic predilection toward disease
      occurrence. We present a rare case of idiopathic gingival fibromatosis associated
      with generalized aggressive periodontitis in a young female. The patient
      presented with classic clinical and radiographic presentation associated with
      gingival enlargement and aggressive periodontitis. The diagnosis was then
      confirmed by histopathological and neutrophil functions tests. 

PMID- 24872639
TI  - Systemic antimicrobial therapy (minocycline) as an adjunct to non-surgical
      approach to recurrent chronic generalized gingival hyperplasia.
AB  - Systemic antibiotic treatment has emerged as a powerful adjunct to conventional
      mechanical debridement for therapeutic management of the periodontal diseases.
      The conceptual basis for treating periodontal diseases as infections is
      particularly attractive in part because of substantial data indicating that these
      diseases may be associated with specific putative pathogens. Further, discrete
      groups of patients respond well to systemic antibiotics and exhibit improvement
      of clinical parameters, including attachment level and inflammation. This
      bacterial-host interaction, which is ever-so-present in periodontitis, directs us
      toward utilizing antimicrobial agents along with the routine mechanical
      debridement. This case report presents a case of a female patient with recurrence
      of the chronic generalized periodontitis with gingival enlargement, which is
      treated thrice by referral dentist. A through clinical examination was carried
      out pre-operatively and treatment was planned with systemic minocycline in
      conjunction with the conventional non-surgical approach. There was a significant
      reduction of pocket depth, gain in attachment with dramatic improvement
      clinically. 

PMID- 24872640
TI  - Lip repositioning.
AB  - Excessive gingival display is a frequent finding that can occur because of
      various intraoral or extraoral etiologies. This report describes the use of
      surgical lip repositioning technique for the management of a gummy smile
      associated with vertical maxillary excess and hypermobility of the upper lip. The
      procedure restricts the muscle pull of the elevator lip muscles by shortening the
      vestibule, thus reducing the gingival display when smiling. Healing was
      uneventful and follow-up examinations of 10 months revealed reduced gingival
      display. For patients desiring a less invasive alternative to orthognathic
      surgery, lip repositioning is a viable alternative. 

PMID- 24872641
TI  - Laser excision of peripheral ossifying fibroma: Report of two cases.
AB  - Peripheral ossifying fibroma (POF) is a non-neoplastic enlargement seen more
      often in females, in the interdental papilla and the anterior part of the
      maxilla, accounts for about 9% of all gingival growths. Of unknown etiology,
      unpredictable clinical course and pronicity for recurrence, POF is a clinician's
      cause for concern. Surgical excision is the treatment of choice, but with a
      reported recurrence rate of 7-45%, the management is often frustrating. With
      increasing acceptance of lasers in the repertoire of clinician's armory, laser
      excision of such lesions has become a possible, feasible, and patient-preferred
      approach. The purpose of this article is to report successful management and 1
      year follow-up of two cases of POF using neodymium-doped yttrium aluminum garnet
      (Nd: YAG) laser. The absence of operative bleeding, relative ease of the
      procedure and patient acceptance lends the laser excision as an alternate
      therapeutic modality for excision of gingival enlargements of suspicious and
      vexatious nature. 

PMID- 24872642
TI  - Reconstructive surgery with chin block graft and esthetic rehabilitation of
      missing anterior tooth.
AB  - The complete and predictable restoration of the periodontium following infection
      or trauma remains a critical objective in regenerative therapy. Bone grafts
      remain among the most widely used therapeutic strategies for the correction of
      periodontal osseous defects. For periodontally compromised anterior teeth,
      reconstruction of the ridge along with natural tooth pontic serves both the
      purpose of regeneration and esthetics. The right lower central incisor of a 28
      year-old male that was periodontally compromised was extracted. Autogenous chin
      grafting followed by retrograde surgery of the extracted tooth and replacement by
      natural tooth pontic was done. After 6 months, there was significant improvement
      in clinical picture and bone fill. This procedure provided excellent regenerative
      and esthetic results for the periodontally compromised lost anterior tooth. 

PMID- 24872644
TI  - Ultrasound in the critically ill: Look for Lung water!

PMID- 24872643
TI  - A staged approach of implant placement in immediate extraction sockets for
      preservation of peri-implant soft and hard tissue.
AB  - Esthetic zone restoration is a challenging aspect in implant dentistry because of
      two critical factors such as level of bone support and soft tissue dimensions.
      Preservation of healthy peri-implant tissues is of primary importance for
      ensuring better esthetics over an extended period. The aim of the present case
      series was to evaluate a new staged approach of implant placement in immediate
      extraction sockets for preservation of peri-implant soft and hard tissues. Four
      subjects scheduled for extraction of teeth in the esthetic zone with neither a
      periapical nor periodontal infection and with thick tissue biotype were included.
      For all the subjects sand blasted, large grit, acid etched platform switched
      implant with a diameter 2 mm less than the diameter of extraction socket and a
      conical abutment-implant connection (Morse taper) were placed 2 mm below the
      crest of the socket, with almost 2 mm gap between the labial plate and the
      implant with shoulder placed palatally/lingually. The implants were loaded after
      2 months healing period and followed for a period of 1-2 years. In all the four
      patients there was preservation of both hard and soft tissues around the implant
      with a good esthetic outcome in all the follow up visits. Integrating immediate
      placement with stable implant-abutment connection, platform switching concept and
      careful case selection, we can achieve a very good esthetic outcome. 

PMID- 24872645
TI  - Sleep quality in intensive care unit: Are we doing our best for our patients?

PMID- 24872646
TI  - Characterizing sepsis: Another small piece of the puzzle.

PMID- 24872647
TI  - Transthoracic ultrasound assessment of B-lines for identifying the increment of
      extravascular lung water in shock patients requiring fluid resuscitation.
AB  - INTRODUCTION: Several studies have shown that the number of B-lines was related
      to the amount of extravascular lung water (EVLW). In our study, we aimed to
      demonstrate the magnitude of the incremental B-lines in shock patients with
      positive net fluid balance and the association with gas exchange impairment.
      MATERIALS AND METHODS: We performed trans-thoracic ultrasound at admission (T0)
      and at follow-up period (TFL) to demonstrate the change of B lines (DeltaB-lines)
      after fluid therapy. We compared the total B-line score (TBS) at T0 and TFL and
      calculated the Pearson's correlation coefficient between the DeltaB-lines and
      PaO2/FiO2 ratio. RESULTS: A total of 20 patients were analyzed. All patients had
      septic shock. Net fluid balance was + 2228.05 +/- 1982.15 ml. The TBS at T0 and
      TFL were 36.6 +/- 23.73 and 63.80 +/- 29.25 (P < 0.01). The DeltaB-lines along
      anterior axillary line (AAL) correlated to the DeltaTBS (r = 0.90, P < 0.01). The
      DeltaB-lines along AAL had inverse correlation to PaO2/FiO2 ratio (r = -0.704, P
      < 0.05). The increase of B-lines >= 10 was related to the decrease of PaO2/FiO2
      ratio. The inter-observer reliability between two ultrasound readers was high (r
      = 0.92, P < 0.01). DISCUSSION: The number of B-lines increased in shock patients
      with positive net fluid balance and correlated to impaired oxygenation. These
      data supported the benefit of ultrasound for assessing the EVLW.

PMID- 24872648
TI  - Ventilator-associated pneumonia in a tertiary care intensive care unit: Analysis
      of incidence, risk factors and mortality.
AB  - BACKGROUND: Ventilator-associated pneumonia (VAP) is the most common nosocomial
      infection diagnosed in the intensive care unit (ICU) and in spite of advances in
      diagnostic techniques and management it remains a common cause of hospital
      morbidity and mortality. OBJECTIVE: The primary objective of the following study
      is to determine the incidence, various risk factors and attributable mortality
      associated with VAP and secondary objective is to identify the various bacterial
      pathogens causing VAP in the ICU. MATERIALS AND METHODS: This prospective
      observational study was carried out over a period of 1 year. VAP was diagnosed
      using the clinical pulmonary infection score. Endotracheal aspirate (ETA) and
      bronchoalveolar lavage (BAL) samples of suspected cases of VAP were collected
      from ICU patients and processed as per standard protocols. STATISTICAL ANALYSIS:
      Fisher's exact test was applied when to compare two or more set of variables were
      compared. RESULTS: The incidence of VAP in our study was 57.14% and the incidence
      density of VAP was 31.7/1000 ventilator days. Trauma was the commonest underlying
      condition associated with VAP. The incidence of VAP increased as the duration of
      mechanical ventilation increased and there was a total agreement in bacteriology
      between semi-quantitative ETAs and BALs in our study. The overall mortality
      associated with VAP was observed to be 48.33%. CONCLUSIONS: The incidence of VAP
      was 57.14%. Study showed that the incidence of VAP is directly proportional to
      the duration of mechanical ventilation. The most common pathogens causing VAP
      were Acinetobacter spp. and Pseudomonas aeruginosa and were associated with a
      high fatality rate.

PMID- 24872649
TI  - Association between heat shock protein 70 gene polymorphisms and clinical
      outcomes in intensive care unit patients with sepsis.
AB  - OBJECTIVE: The objective of the following study is to evaluate the associations
      between single nucleotide polymorphisms (SNPs) in the Heat Shock Protein 70
      (HSP70) gene, gene expression of interleukin-6 (IL-6) and tumor necrosis factor
      alpha (TNF-alpha) and medical intensive care unit (MICU) stay and organ failure
      in sepsis. MATERIALS AND METHODS: MICU patients with sepsis were genotyped for
      rs1061581, rs2227956, rs1008438 and rs1043618 polymorphisms in HSP70 gene using
      polymerase chain reaction (PCR)-restriction fragment length polymorphism analysis
      or allele-specific PCR. Messenger ribonucleic acid (mRNA) expression of IL-6 and
      TNF-alpha were quantitated in peripheral blood lymphocytes. Outcomes were
      recorded. RESULTS: 108 patients (48 male) aged 40.7 +/- 16.0 (mean +/- standard
      deviation) years included H1N1 infection (36), scrub typhus (29) and urosepsis
      (12). Seventy-one (65.7%) had dysfunction of three or more organ systems, 66
      patients (61.1%) were treated by mechanical ventilation, 21 (19.4%) needed
      dialysis. ICU stay was 9.3 +/- 7.3 days. Mortality was 38.9%. One or more SNPs
      were noted in 101/108 (93.5%) and organ failure was noted in only 1/7 patients
      without a single SNP. The A allelotypes of rs1061581 and rs1008438 were
      associated with hematological dysfunction (P = 0.03 and 0.07) and longer ICU stay
      (P = 0.05 and 0.04), whereas IL-6 and TNF-alpha mRNA levels were associated with
      central nervous system dysfunction. CONCLUSIONS: HSP70 genotypes may determine
      some adverse outcomes in patients with sepsis.

PMID- 24872650
TI  - Propofol versus flunitrazepam for inducing and maintaining sleep in postoperative
      ICU patients.
AB  - CONTEXT: Sleep deprivation is a common problem on intensive care units (ICUs)
      influencing not only cognition, but also cellular functions. An appropriate sleep
      wake cycle should therefore be maintained to improve patients' outcome. Multiple
      disruptive factors on ICUs necessitate the administration of sedating and sleep
      promoting drugs for patients who are not analgo-sedated. AIMS: The objective of
      the present study was to evaluate sleep quantity and sleep quality in ICU
      patients receiving either propofol or flunitrazepam. SETTINGS AND DESIGN:
      Monocentric, randomized, double-blinded trial. MATERIALS AND METHODS: A total of
      66 ICU patients were enrolled in the study (flunitrazepam n = 32, propofol n =
      34). Propofol was injected continuously (2 mg/kg/h), flunitrazepam as a bolus
      dose (0.015 mg/kg). Differences between groups were evaluated using a
      standardized sleep diary and the bispectral index (BIS). STATISTICAL ANALYSIS
      USED: Group comparisons were performed by Mann-Whitney U-Test. P < 0.05 was
      considered to be statistically significant. RESULTS: Sleep quality and the
      frequency of awakenings were significantly better in the propofol group (Pg). In
      the same group lower BIS values were recorded (median BIS propofol 74.05,
      flunitrazepam 78.7 [P = 0.016]). BIS values had to be classified predominantly to
      slow-wave sleep under propofol and light sleep after administration of
      flunitrazepam. Sleep quality improved in the Pg with decreasing frequency of
      awakenings and in the flunitrazepam group with increasing sleep duration.
      CONCLUSIONS: Continuous low-dose injection of propofol for promoting and
      maintaining night sleep in ICU patients who are not analgo-sedated was superior
      to flunitrazepam regarding sleep quality and sleep structure.

PMID- 24872651
TI  - Scoring systems in the intensive care unit: A compendium.
AB  - Severity scales are important adjuncts of treatment in the intensive care unit
      (ICU) in order to predict patient outcome, comparing quality-of-care and
      stratification for clinical trials. Even though disease severity scores are not
      the key elements of treatment, they are however, an essential part of improvement
      in clinical decisions and in identifying patients with unexpected outcomes.
      Prediction models do face many challenges, but, proper application of these
      models helps in decision making at the right time and in decreasing hospital
      cost. In fact, they have become a necessary tool to describe ICU populations and
      to explain differences in mortality. However, it is also important to note that
      the choice of the severity score scale, index, or model should accurately match
      the event, setting or application; as mis-application, of such systems can lead
      to wastage of time, increased cost, unwarranted extrapolations and poor science.
      This article provides a brief overview of ICU severity scales (along with their
      predicted death/survival rate calculations) developed over the last 3 decades
      including several of them which has been revised accordingly. 

PMID- 24872652
TI  - Glycemic control in critically ill: A moving target.
AB  - Glycemic control targets in intensive care units (ICUs) have three distinct
      domains. Firstly, excessive hyperglycemia needs to be avoided. The upper limit of
      this varies depending on the patient population studied and diabetic status of
      the patients. Surgical patients particularly cardiac surgery patients tend to
      benefit from a lower upper limit of glycemic control, which is not evident in
      medically ill patient. Patient with premorbid diabetic status tends to tolerate
      higher blood sugar level better than normoglycemics. Secondly, hypoglycemia is
      clearly detrimental in all groups of critically ill patient and all measures to
      avoid this catastrophe need to be a part of any glycemic control protocol.
      Thirdly, glycemic variability has increasingly been shown to be detrimental in
      this patient population. Glycemic control protocols need to take this into
      consideration and target to reduce any of the available metrics of glycemic
      variability. Newer technologies including continuous glucose monitoring
      techniques will help in titrating all these three domains within a desirable
      range. 

PMID- 24872653
TI  - Nosocomial candiduria in chronic liver disease patients at a hepatobilliary
      center.
AB  - BACKGROUND: Nosocomial urinary tract infections (UTIs) are common in catheterized
      patients. Fungal UTI has become an important nosocomial problem over the past
      decade. The microbiology of candiduria is rapidly evolving and new trends are
      being reported. AIMS: To study the microbiological trends and antifungal
      resistance profile of Candida in urine of catheterized chronic liver disease
      (CLD) patients at a super specialty hepatobiliary tertiary-care center. MATERIALS
      AND METHODS: urine samples were collected by sterile technique, processed by semi
      quantitative method as per the standard protocols. Direct microscopic examination
      of urine sample was also done to look for the presence of pus cells, red blood
      cells, casts, crystals or any bacterial or fungal element. RESULT: A total of 337
      yeast isolates were obtained from catheterized patients, non-albicans Candida
      spp. emerged as the predominant pathogen and was responsible for 67.06% of
      nosocomial fungal UTI. Candida tropicalis accounted for 34.71% of the cases,
      whereas Candida albicans grew in 32.93%, Candida glabrata 16.32%, rare Candida
      spp. Nearly 11.5% (Candida hemolunii to be confirmed by molecular methods).
      Antifungal sensitivity varied non-albicans species except C. tropicalis, Candida
      parapsilosis were more often resistant to antifungal drugs. CONCLUSION:
      Nosocomial Candida UTIs in CLD patients is common, due to the cumulative pressure
      of contributing factors such as urinary instrumentation and prolonged use of
      broad-spectrum antibiotics. Non-albicans Candida were found to outnumber C.
      albicans in catherized CLD patients. Risk of strain persistence is also higher
      with non-albicans Candida. Thus, species identification and susceptibility
      testing is a must for appropriate management of such patients.

PMID- 24872654
TI  - Spiked helmet sign: An under-recognized electrocardiogram finding in critically
      ill patients.
AB  - A 77-year-old male patient presented with rhabdomyolysis. He developed
      progressive respiratory failure and acute respiratory distress syndrome during
      his hospital stay requiring mechanical ventilation. An electrocardiogram during
      mechanical ventilation showed findings suggestive of ST elevation myocardial
      infarction. Closer review showed dome and spike findings that have been likened
      to a "spiked helmet." This finding has been associated with significant
      mortality. We discuss this under-recognized finding and the potential
      contributing mechanisms. 

PMID- 24872655
TI  - Guillain-Barre syndrome complicated by acute fatal rhabdomyolysis.
AB  - Guillain-Barre syndrome (GBS) is a heterogenous group of peripheral-nerve
      disorders with similar clinical presentation characterized by acute, self
      limited, progressive, bilateral and relatively symmetric ascending flaccid
      paralysis, which peaks in 2-4 weeks and then subsides. The usual complications,
      which occur in a patient of GBS are pneumonia, sepsis, pulmonary embolism,
      respiratory insufficiency and cardiac arrest. The clinical course of GBS
      complicated by acute rhabdomyolysis is extremely rare. We present the case of GBS
      with marked elevation in serum creatine kinase, serum myoglobin levels and
      persistent hyperkalemia as a result of associated acute rhabdomyolysis. 

PMID- 24872657
TI  - High dose intravenous immunoglobulin may be complicated by myocardial infarction.
AB  - Intravenous immunoglobulin [IVIg] is useful for treating several clinical
      conditions and is largely considered safe, without major adverse events. Here we
      report a case of acute ST elevation myocardial infarction associated with high
      dose IVIg administration in a previously healthy 69-year-old male patient of
      Guillain Barre syndrome. The case is being reported to emphasize the need for
      treating physicians to be aware of thrombotic complications associated with IVIg.
      The thrombotic complications associated with IVIg are reviewed in brief, and the
      measures to reduce them are discussed. 

PMID- 24872656
TI  - Atypical manifestations of organophosphorus poisoning following subcutaneous
      injection of Dichlorvos with suicidal intention.
AB  - Current case report describes a 37-year-old female patient who was admitted to
      the hospital following subcutaneous injection of Dichlorvos with an insulin
      syringe. The only peripheral cholinergic sign observed on admission was excessive
      salivation with bilateral pyramidal tract signs. Locally she had necrosis of skin
      and subcutaneous tissue with surrounding blisters. In the subsequent course of
      her illness, she developed respiratory arrest requiring ventilator support. She
      also had delayed extrapyramidal manifestations. Relevant literature is reviewed.
      Possibility of route-specific, delayed predominant central nervous system effect
      of Dichlorvos postulated. 

PMID- 24872658
TI  - Posterior reversible encephalopathy syndrome in a patient of organophosphate
      poisoning.
AB  - A 32-year-old male presented with a history of consuming some organophosphorous
      compound with suicidal intention. He was treated with atropine, pralidoxime,
      ventilator support. During stay patient had persistent irritability,
      tachycardiaand hypertension despite sedation and labetalol infusion. He developed
      headache, visual blurring hemiparesis and focal seizures. Magnetic resonance
      imaging of the brain revealed multifocal hyperintensities mainly in subcortical
      areas of parietal and occipital regions in T2-weighted images, with increased
      values of Apparent Diffusion Coefficient, suggesting posterior reversible
      encephalopathy syndrome (PRES). The possibilities of PRES caused by
      organophosphorous poisoning either due to hypertension caused by autonomic
      deregulation or direct neurological toxicity has been discussed. 

PMID- 24872659
TI  - Methylene blue unresponsive methemoglobinemia.
AB  - Acquired methemoglobinemia is an uncommon blood disorder induced by exposure to
      certain oxidizing agents and drugs. Although parents may not give any history of
      toxin ingestion; with the aid of pulse-oximetry and blood gas analysis, we can
      diagnose methemoglobinemia. Prompt recognition of this condition is required in
      emergency situations to institute early methylene blue therapy. We report an
      unusual case of severe toxic methemoglobinemia, which did not respond to
      methylene blue, but was successfully managed with exchange transfusion. 

PMID- 24872660
TI  - Difficult extubation after large tongue swelling in intensive care unit.

PMID- 24872661
TI  - Snake bite and stroke: Our experience of two cases.

PMID- 24872662
TI  - The anticonvulsant of choice in pyrethroid induced convulsions.

PMID- 24872663
TI  - Is gastric residual volume monitoring in critically ill patients receiving
      mechanical ventilation an evidence-based practice?

PMID- 24872664
TI  - "DIRECT CPR"- Mnemonic to remember 2010 AHA BLS CPR guidelines.

PMID- 24872665
TI  - Safe development of nanotechnology: A global challenge.

PMID- 24872666
TI  - The healthy organization construct: A review and research agenda.
AB  - Work plays an important role in one's life for many reasons. It provides us with
      economic, social, and personal satisfaction and accounts for a substantial
      percentage of our waking hours. But in today's knowledge-driven economy,
      organization of work has been changing at a warp speed as a consequence of
      economic, social and technological aspects of changes brought down by
      globalization and liberalization worldwide. While this situation has eliminated
      some risks of the earlier industrial era, it is introducing others. In such a
      dynamic business environment, where can business leaders and managers find
      competitive advantage? It lies in balancing people and performance goals. This is
      the line of approach for healthy organization research that examines
      organizational context with regard to: People, work organization, management
      practices, employee wellbeing and performance. The healthy organization concept
      proposes that along with the profits, employee's well being should also be an
      important goal for organizations. In this paper, the researcher undertakes an
      extensive review of literature in the mainstream business literature and
      establishes the agenda for healthy organization research among other research
      paradigms. 

PMID- 24872667
TI  - Prevalence of Chronic Mountain Sickness in high altitude districts of Himachal
      Pradesh.
AB  - INTRODUCTION: Chronic Mountain Sickness (CMS) is a maladaptation condition that
      can affect people who reside permanently at high altitude (HA). It is
      characterized by polycythemia, hypoxemia and dyspnea and can be fatal. Over 140
      million people live permanently at HA around the world. Unfortunately, research
      into CMS is lacking and accurate data on the prevalence of this condition do not
      exist for many regions around the world. In this study, we sought to examine
      prevalence rates of CMS in the Indian Himalayas, focusing on the Northern State
      of Himachal Pradesh. MATERIALS AND METHODS: We surveyed 83 individuals (69 males)
      in eight towns across the HA districts of Sirmaur, Kinnaur and Lahaul and Spiti
      in Himachal Pradesh, India. Altitudes ranged from 2350 to 4150 m. We used an
      adapted Qinghai CMS scoring system to diagnose CMS. Information related to
      subject demographics, medical history, socioeconomic status, and geography were
      collected to identify risk factors for CMS. Physiologic recordings of oxygen
      saturation (SpO2) and pulse rate were made through pulse oximetry. RESULTS:
      Overall CMS prevalence was 6.17% and mean altitude was 3281 m. At altitudes above
      3000 m CMS prevalence rose to 13.73%. All cases of CMS were mild and there was a
      significant positive correlation between CMS scores and altitude (R = 0.784, P =
      0.0213). Mean SpO2 was 90.7 +/- 0.4% and mean pulse rate was 80.3 +/- 1.3 bpm.
      SpO2 significantly correlated with altitude (R = -0.929, P < 0.001). In our
      study, age, gender, and tobacco use were not independent risk factors for CMS.
      Individuals with CMS lived at higher altitudes than their non-CMS counterparts
      (3736.00 +/- 113.30 m vs. 3279.80 +/- 69.50 m, respectively; P = 0.017).
      CONCLUSION: CMS prevalence in HA towns of the Indian Himalayas of Himachal
      Pradesh is 6.17% and 13.73% for towns above 3000 m. Further research is required
      to determine the prevalence of CMS in other regions of the world and to determine
      risk factors associated with CMS.

PMID- 24872668
TI  - Job stress and hypertension in younger software professionals in India.
AB  - BACKGROUND: We report the results of a moderately large study (1071) to study the
      prevalence of hypertension among software professionals in the Indian
      subcontinent employed at 27 different companies in Bangalore. The focus of our
      study is on the age gradient of hypertension prevalence and exploring the
      association of workplace psychosocial predictors of hypertension. MATERIALS AND
      METHODS: We used mixed methods sampling strategy, the first stage of which
      involved stratified sampling to select the clusters of software companies in
      Bangalore and the second stage involved selecting individual companies through
      purposive sampling. Job stress questionnaire was self-administered to collect
      information on job stress and blood pressure classification is done based on 7
      (th) report of Joint National Commission. RESULTS: The prevalence of hypertension
      among Information Technology/Information Technology Enabled Services
      professionals was 31% and pre-hypertension was 45.7%. The prevalence of stage-1
      hypertension in the age group of 19-25 years was 18% and 23% in 26-30 years group
      while the prevalence of stage-2 hypertension in the age group of 19-25 years was
      5% and 3% in 26-30 years group. The results indicate that dimensions of workplace
      autonomy and workplace environment are associated with hypertension. CONCLUSIONS:
      Hypertension affects the young urban Indians a decade earlier compared to
      available evidence. Furthermore, there is an association of autonomy and work
      environment with hypertension. This signifies further exploration of underlying
      endocrine mechanisms. FUNDING: The funding UCLA International Research and
      Training Program and the Public Health Foundation of India provided the funding
      for this study. RESULTS: THE STUDY WAS SUPPORTED THROUGH FOGARTY/UCLA
      INTERNATIONAL RESEARCH AND TRAINING PROGRAM (GRANT NUMBER: D43 TW000013) and the
      Public Health Foundation of India.

PMID- 24872669
TI  - Study the epidemiological profile of taxi drivers in the background of
      occupational environment, stress and personality characteristics.
AB  - BACKGROUND: Work hazards have been a major cause of concern in driving industry
      especially in taxi drivers. This study integrates the various factors that
      influence physical and emotional well-being of taxi drivers into the theoretical
      model that shows that the work environment, stress and personality
      characteristics directly influence taxi drivers' health. OBJECTIVE: The aim of
      the following study is to study the relative and combined influence of work
      environment, personality characteristics and stress on the health of taxi
      drivers. MATERIALS AND METHODS: [corrected] The present study is cross-sectional
      (descriptive) study taxi drivers in Mumbai. They are selected using multistage
      random sampling method. Calculated sample size is 508. Data produced after the
      survey is analyzed using IBM SPSS 16.0 software. RESULTS: Nearly 65% of taxi
      drivers belonged to middle-age group of 21-40 years of age. Majority (59%) of
      taxi drivers belonged to the lower upper socio-economic class. 70% of taxi
      drivers worked for more than 8 h daily. 63% gave the history of one or more
      addictions. 52% taxi drivers had type B1 personality, only 6% had stress prone
      and aggressive type A1 personality. Traffic congestion (67.1%) was reported as
      the leading stressor followed by narrow bottle neck roads (43%), too many speed
      breakers (41%), rude gestures and behavior by other drivers (42%) and bad weather
      (36%). Nearly 86% taxi drivers had one or more symptoms of morbidities.
      Gastrointestinal symptoms predominated followed by musculoskeletal symptoms and
      depression. CONCLUSION: Socio-demographic attributes, work environment, stress
      and personality significantly influence physical and psychological morbidities in
      taxi drivers.

PMID- 24872670
TI  - Non-hodgkin's lymphoma and work in agriculture: Results of a two case-control
      studies in Saskatchewan, Canada.
AB  - OBJECTIVES: The objective was to examine the association between non-Hodgkin's
      lymphoma (NHL) and farming-related activities, gender, pesticides exposure, and
      exposure to chemicals other than pesticides in Saskatchewan. MATERIALS AND
      METHODS: Male and female study participants were taken from two separate case
      control studies conducted in Saskatchewan province, Canada. A case was defined as
      any man or woman aged 19 years and older with a first diagnosis of NHL registered
      by the Saskatchewan Cancer Agency during the study period. Conditional logistic
      regression was used to fit the statistical models. RESULTS: Farming exposure and
      exposure to pesticides-contaminated cloths were related to an increased risk of
      NHL. Exposure to pesticides was strongly associated with an increased risk of
      NHL, especially for men. CONCLUSION: For men, the incidence of NHL was associated
      with exposure to pesticides after adjusting for other independent predictors.

PMID- 24872671
TI  - Pleural mesothelioma in a couple of brothers.
AB  - Malignant mesotheliomas of the pleura, epithelial type, were observed in two
      brothers. Both the patients had histories of severe exposure to asbestos, having
      worked as insulators. The latency periods in the two cases were 26 and 38 years,
      respectively. Available literature data suggest that mesothelioma occurrence
      among blood-related people is favored by a genetic predisposition. 

PMID- 24872672
TI  - From the nurses view point.

PMID- 24872674
TI  - Prismatic displacement effect of progressive multifocal glasses on reaction time
      and accuracy in elderly people.
AB  - BACKGROUND: Multifocal glasses (bifocals, trifocals, and progressives) increase
      the risk of falling in elderly people, but how they do so is unclear. To explain
      why glasses with progressive addition lenses increase the risk of falls and
      whether this can be attributed to false projection, this study aimed to 1) map
      the prismatic displacement of a progressive lens, and 2) test whether this
      displacement impaired reaction time and accuracy. METHODS: The reaction times of
      healthy >=75-year-olds (31 participants) were measured when grasping for a bar
      and touching a black line. Participants performed each test twice, wearing their
      progressives and new, matched single vision (distance) glasses in random order.
      The line and bar targets were positioned according to the maximum and minimum
      prismatic displacement effect through the progressive lens, mapped using a
      focimeter. RESULTS: Progressive spectacle lenses have large areas of prismatic
      displacement in the central visual axis and edges. Reaction time was faster for
      progressives compared with single vision glasses with a centrally-placed
      horizontal grab bar (mean difference 101 ms, P=0.011 [repeated measures
      analysis]) and a horizontal black line placed 300 mm below center (mean
      difference 80 ms, P=0.007). There was no difference in accuracy between the two
      types of glasses. CONCLUSION: Older people appear to adapt to the false
      projection of progressives in the central visual axis. This adaptation means that
      swapping to new glasses or a large change in prescription may lead to a fall.
      Frequently updating glasses may be more beneficial.

PMID- 24872673
TI  - An emerging treatment option for glaucoma: Rho kinase inhibitors.
AB  - Rho kinase (ROCK) inhibitors are a novel potential class of glaucoma therapeutics
      with multiple compounds currently in Phase II and III US Food and Drug
      Administration trials in the United States. These selective agents work by
      relaxing the trabecular meshwork through inhibition of the actin cytoskeleton
      contractile tone of smooth muscle. This results in increased aqueous outflow
      directly through the trabecular meshwork, achieving lower intraocular pressures
      in a range similar to prostaglandins. There are also animal studies indicating
      that ROCK inhibitors may improve blood flow to the optic nerve, increase ganglion
      cell survival, and reduce bleb scarring in glaucoma surgery. Given the multiple
      beneficial effects for glaucoma patients, ROCK inhibitors are certainly a highly
      anticipated emerging treatment option for glaucoma. 

PMID- 24872675
TI  - Managing adverse effects of glaucoma medications.
AB  - Glaucoma is a chronic, progressive disease in which retinal ganglion cells
      disappear and subsequent, gradual reductions in the visual field ensues. Glaucoma
      eye drops have hypotensive effects and like all other medications are associated
      with adverse effects. Adverse reactions may either result from the main agent or
      from preservatives used in the drug vehicle. The preservative benzalkonium
      chloride, is one such compound that causes frequent adverse reactions such as
      superficial punctate keratitis, corneal erosion, conjunctival allergy, and
      conjunctival injection. Adverse reactions related to main hypotensive agents have
      been divided into those affecting the eye and those affecting the entire body. In
      particular, beta-blockers frequently cause systematic adverse reactions,
      including bradycardia, decrease in blood pressure, irregular pulse and asthma
      attacks. Prostaglandin analogs have distinctive local adverse reactions,
      including eyelash bristling/lengthening, eyelid pigmentation, iris pigmentation,
      and upper eyelid deepening. No systemic adverse reactions have been linked to
      prostaglandin analog eye drop usage. These adverse reactions may be minimized
      when they are detected early and prevented by reducing the number of different
      eye drops used (via fixed combination eye drops), reducing the number of times
      eye drops are administered, using benzalkonium chloride-free eye drops, using
      lower concentration eye drops, and providing proper drop instillation training.
      Additionally, a one-time topical medication can be given to patients to allow
      observation of any adverse reactions, thereafter the preparation of a topical
      medication with the fewest known adverse reactions can be prescribed. This does
      require precise patient monitoring and inquiries about patient symptoms following
      medication use. 

PMID- 24872676
TI  - Delayed macular hole formation after demarcation laser photocoagulation for
      subclinical retinal detachment.
AB  - The purpose of this paper is to report a series of macular holes that developed
      after demarcation laser photocoagulation for subclinical retinal detachments.
      This observational case series consists of three eyes from three patients seen
      between 2005 and 2012. Delayed idiopathic macular hole formation occurred
      following demarcation laser photocoagulation for subclinical retinal detachment.
      Demarcation laser photocoagulation of subclinical retinal detachments may
      predispose to macular hole formation. 

PMID- 24872677
TI  - Inhibition of B7-1 (CD80) by RhuDex(r) reduces lipopolysaccharide-mediated
      inflammation in human atherosclerotic lesions.
AB  - BACKGROUND: Atherosclerosis is based on a chronic inflammatory process including
      the innate and adaptive immune response. Costimulatory molecules and their
      receptors provide decisive signals for antigen-specific cell activation. The
      contribution of B7-related pathways to atherosclerosis has hardly been explored.
      METHODS: In the present study, we investigated the contribution of B7-1 to
      inflammation and tissue injury in the human plaque microenvironment in order to
      identify possible target structures of future therapeutic agents ex vivo and in
      vitro. RESULTS: Carotid artery plaque stimulation with lipopolysaccharides (LPS)
      could be significantly inhibited by RhuDex((r)), a specific inhibitor of the
      costimulatory molecule B7-1 ex vivo (P<0.001). Coculture of antigen-presenting
      cells with T-cells demonstrated that the inhibitory effects of RhuDex((r))
      derived from reduced T-cell activation. In addition, incubation of
      monocytes/macrophages with LPS and RhuDex((r)) resulted in an inhibitory negative
      feedback on antigen-presenting cells. Signaling pathways affected by RhuDex((r))
      seem to be nuclear transcription factor kappa B, activator protein-1, and
      extracellular signal-regulated kinase 1/2. CONCLUSION: The present data support
      B7-1 alone as an important costimulatory molecule in the context of LPS-mediated
      inflammation in atherosclerotic lesions. Due to its marked inhibitory effects,
      RhuDex((r)) may be a useful therapy to modulate the inflammatory milieu in
      atherosclerosis.

PMID- 24872678
TI  - P-glycoprotein- and organic anion-transporting polypeptide-mediated transport of
      periplocin may lead to drug-herb/drug-drug interactions.
AB  - Periplocin, an active and toxic component of the traditional Chinese herbal
      medicine Periploca sepium Bge, is a cardiac glycoside compound that has been
      implicated in various clinical accidents. This study investigated the role of
      transporters in the intestinal absorption and biliary excretion of periplocin, as
      well as the possible metabolic mechanism of periplocin in liver S9. In a
      bidirectional transport assay using Madin-Darby canine kidney (MDCK) and MDCK
      multidrug-resistance protein (MRP)-1 cell monolayers, both in situ intestinal and
      liver-perfusion models were used to evaluate the role of efflux and uptake
      transporters on the absorption and biliary excretion of periplocin. In addition,
      in vitro metabolism of periplocin was investigated by incubating with human/rat
      liver S9 homogenate fractions to evaluate its metabolic mechanisms in liver
      metabolic enzymes. The results showed that P-glycoprotein (P-gp) was involved in
      the intestinal absorption of periplocin, whereas MRP2 and breast cancer
      resistance protein were not. The efflux function of P-gp may be partly
      responsible for the low permeability and bioavailability of periplocin. Moreover,
      both inhibitors of P-gp and organic anion-transporting polypeptides (OATPs)
      increased periplocin biliary excretion. No obvious indications of metabolism were
      observed in the in vitro incubation system, which suggests that periplocin did
      not interact with the hepatic drug metabolic enzymes. The results of this study
      showed that the efflux and uptake transporters P-gp and OATPs were involved in
      the absorption and biliary excretion of periplocin, which may partially account
      for its low permeability and bioavailability. As a toxic compound, potential drug
      herb/herb-herb interactions based on OATPs and P-gp should be taken into account
      when using P. sepium Bge in the clinic. 

PMID- 24872679
TI  - Identification of a novel potential antitumor activity of gossypol as an APE1/Ref
      1 inhibitor.
AB  - The human apurinic/apyrimidinic endonuclease 1/redox enhancing factor-1 (APE1/Ref
      1), an essential multifunctional protein involved in the repair of oxidative
      deoxyribonucleic acid (DNA) damage and transcriptional regulation, is often
      overexpressed in tumor tissues and cancer cells. Moreover, APE1/Ref-1 (APE1)
      overexpression has been linked to chemoresistance in human tumors. Thus,
      inhibiting APE1 function in cancer cells is considered a promising strategy to
      overcome resistance to therapeutic agents. Gossypol is a Bcl-2 homology 3 (BH3)
      mimetic agent and is able to bind to the BH3 domain of B-cell lymphoma 2 (Bcl-2)
      family members. Other studies demonstrated that Bcl-2 directly interacted with
      APE1 via its BH domains. Using apurinic/apyrimidinic (AP) endonuclease assays, we
      found that gossypol inhibits the repair activity of APE1. Electrophoretic
      mobility shift assays and dual luciferase assays showed that gossypol could also
      inhibit the redox function of APE1. Using dual polarization interferometry
      technology, we show that gossypol can directly interact with APE1. Furthermore,
      addition of gossypol, in conjunction with APE1 overexpression, leads to cancer
      cell death. The addition of gossypol also enhances the cell killing effect of the
      laboratory alkylating agent methyl methanesulfonate and the clinical agent
      cisplatin (DDP). Administration of gossypol significantly inhibited the growth of
      xenografts. Furthermore, the combined treatment of gossypol and DDP resulted in a
      statistically higher antitumor activity compared with DDP alone in vivo. In
      conclusion, we have demonstrated that gossypol effectively inhibits the repair
      and redox activity of APE1 through a direct interaction. 

PMID- 24872680
TI  - Transdermal fentanyl for pain due to chemoradiotherapy-induced oral mucositis in
      nasopharyngeal cancer patients: evaluating efficacy, safety, and improvement in
      quality of life.
AB  - This study evaluated the efficacy, safety, and quality of life (QoL) measure of
      transdermal fentanyl (TDF) for moderate-to-severe pain due to oral mucositis
      caused by chemoradiotherapy in patients with advanced nasopharyngeal carcinoma
      (NPC). Patients with NPC who experienced moderate-to-severe oral mucosal pain
      during chemoradiotherapy (n = 78) received TDF for pain relief. Pain relief and
      QoL were compared before and after treatment. The mean numeric rating scale score
      was reduced from 7.41 +/- 0.96 before treatment to 5.54 +/- 0.86, 3.27 +/- 0.73,
      2.88 +/- 0.62, and 2.82 +/- 0.68 on days 1, 4, 7, and 10, respectively, after
      treatment (P < 0.001). Karnofsky performance status and SPAASMS (Score for pain,
      Physical activity levels, Additional pain medication, Additional
      physician/emergency room visits, Sleep, Mood, and Side effects) scores showed
      significant improvement after treatment, indicating an improved QoL of patients
      (both P<0.001). The most common adverse reactions were nausea and vomiting
      (10.26%). No serious life-threatening adverse events and no symptoms of drug
      withdrawal were observed. TDF is effective, safe, and improves QoL in treating
      pain due to oral mucositis caused by chemoradiotherapy in NPC patients.

PMID- 24872681
TI  - Synthesis, antimicrobial, and anti-inflammatory activity, of novel S-substituted
      and N-substituted 5-(1-adamantyl)-1,2,4-triazole-3-thiols.
AB  - The reaction of 5-(1-adamantyl)-4-phenyl-1,2,4-triazoline-3-thione (compound 5)
      with formaldehyde and 1-substituted piperazines yielded the corresponding N
      Mannich bases 6a-f. The reaction of 5-(1-adamantyl)-4-methyl-1,2,4-triazoline-3
      thione 8 with various 2-aminoethyl chloride yielded separable mixtures of the S
      (2-aminoethyl) 9a-d and the N-(2-aminoethyl) 10a-d derivatives. The reaction of
      compound 5 with 1-bromo-2-methoxyethane, various aryl methyl halides, and ethyl
      bromoacetate solely yielded the S-substituted products 11, 12a-d, and 13. The new
      compounds were tested for activity against a panel of Gram-positive and Gram
      negative bacteria and the pathogenic fungus Candida albicans. Compounds 6b, 6c,
      6d, 6e, 6f, 10b, 10c, 10d, 12c, 12d, 12e, 13, and 14 displayed potent
      antibacterial activity. Meanwhile, compounds 13 and 14 produced good dose
      dependent anti-inflammatory activity against carrageenan-induced paw edema in
      rats. 

PMID- 24872683
TI  - Cohort comparisons: emotional well-being among adolescents and older adults.
AB  - BACKGROUND: There are several negative stereotypes about older adults that have
      negatively influenced people's attitude about aging. The present study compared
      emotional well-being between older adults and adolescents. METHODS: Data for this
      study came from 1,403 community-dwelling elderly persons and 1,190 secondary
      school students and were obtained from two national cross-sectional surveys.
      Emotional well-being was measured using the World Health Organization-Five Well
      Being Index. Data analysis was conducted using a multivariate analysis of
      covariance with SPSS software version 20 (IBM Corporation, Armonk, NY, USA).
      RESULTS: Elderly people significantly scored higher levels of emotional well
      being (mean, 62.3; standard deviation, 22.55) than younger people (mean, 57.9;
      standard deviation, 18.46; t, 5.32; P<=0.001). The findings from the multivariate
      analysis of covariance revealed a significant difference between older adults and
      younger people in emotional well-being [F(3, 2587)=120.21; P<=0.001;
      eta(2)=0.122] after controlling for sex. CONCLUSION: Contrary to negative
      stereotypes about aging, our findings show a higher level of emotional well-being
      among older adults compared with younger people.

PMID- 24872682
TI  - The effects of sulodexide on both clinical and molecular parameters in patients
      with mixed arterial and venous ulcers of lower limbs.
AB  - BACKGROUND: Mixed venous and arterial ulcers account for approximately 15%-30% of
      all venous leg ulcerations. Several studies have shown that matrix
      metalloproteinases (MMPs) and neutrophil gelatinase-associated lipocalin (NGAL)
      play a central role in the pathophysiology of venous and arterial diseases. Some
      studies have shown the efficacy of glycosaminoglycans, such as sulodexide (SDX),
      in treating patients with leg ulcers. The aim of this study was to evaluate
      clinical effects of SDX and its correlation with MMPs and NGAL expression in
      patients with mixed arterial and venous leg ulcers. METHODS: Patients eligible
      for this study were of both sexes, older than 20 years, and with a clinical and
      instrumental diagnosis of mixed ulcer. RESULTS: Fifty-three patients of both
      sexes were enrolled and divided into two groups by means of randomization tables.
      Group A (treated group) comprised 18 females and ten males (median age: 68.7
      years) treated with standard treatment (compression therapy and surgery) + SDX
      (600 lipoprotein lipase-releasing units/day intramuscularly) for 15 days followed
      by SDX 250 lipase-releasing units every 12 hours day orally for 6 months as
      adjunctive treatment. Group B (control group) comprised 17 females and eight
      males (median age: 64.2 years) treated with standard treatment only (compression
      therapy and surgery). The type of surgery was chosen according to anatomical
      level of vein incompetence: superficial venous open surgery and/or subfascial
      endoscopic perforating surgery. In all enrolled patients, blood samples were
      collected in order to evaluate the plasma levels of MMPs and NGAL through enzyme
      linked immunosorbent assay. These results were compared to another control group
      (Group C) of healthy individuals. Moreover, biopsies of ulcers were taken to
      evaluate the tissue expression of MMPs and NGAL through Western blot analysis.
      Our results revealed that SDX treatment is able to reduce both plasma levels and
      tissue expression of MMPs improving the clinical conditions in patients with
      mixed ulcers. CONCLUSION: Inhibition of MMPs could represent a possible
      therapeutic intervention to limit the progression of leg ulceration. In
      particular, our findings demonstrate the efficacy of SDX in patients with mixed
      arterial and venous chronic ulcers of the lower limbs.

PMID- 24872684
TI  - Effect of whole-body vibration for 3 months on arterial stiffness in the middle
      aged and elderly.
AB  - BACKGROUND: Cardiovascular disease (CVD) is a common problem of middle-aged and
      older adults. Increased arterial stiffness is a CVD risk factor. Whole-body
      vibration (WBV) is a simple and convenient exercise for middle-aged and older
      adults; however, there have been few studies investigating the effect of WBV on
      arterial stiffness. This study mainly investigated the effect of WBV on arterial
      stiffness in middle-aged and older adults. METHODS: A total of 38 (21 women and
      17 men) middle-aged and elderly subjects (average age, 61.9 years) were randomly
      divided into the WBV group and the control group for a 3-month trial. The WBV
      group received an intervention of 30 Hz and 3.2 g WBV in a natural full standing
      posture at a sports center. The brachial-ankle pulse wave velocity (baPWV), a
      marker of systemic arterial stiffness, and blood pressure and heart rate were
      measured before and after the intervention. RESULTS: After 3 months, there were
      no significant changes in blood pressure or heart rate in both groups. However,
      the bilateral baPWV was significantly reduced in the WBV group (decreased by 0.65
      m/second [P=0.014]; 0.63 m/second [P=0.041] in either side), but not in the
      control group. The comparison between the two groups was not statistically
      significant. CONCLUSION: This study found that 3 months of WBV had a positive
      effect on arterial stiffness in middle-aged and older adults and could therefore
      be regarded as a supplementary exercise. Larger-scale studies are needed to
      confirm the effects of WBV in the future.

PMID- 24872685
TI  - Comparative efficacy of inhaled corticosteroid and long-acting beta agonist
      combinations in preventing COPD exacerbations: a Bayesian network meta-analysis.
AB  - BACKGROUND: A combination therapy with inhaled corticosteroid (ICS) and a long
      acting beta agonist (LABA) is recommended in severe chronic obstructive pulmonary
      disease (COPD) patients experiencing frequent exacerbations. Currently, there are
      five ICS/LABA combination products available on the market. The purpose of this
      study was to systematically review the efficacy of various ICS/LABA combinations
      with a network meta-analysis. METHODS: Several databases and manufacturer's
      websites were searched for relevant clinical trials. Randomized control trials,
      at least 12 weeks duration, comparing an ICS/LABA combination with active control
      or placebo were included. Moderate and severe exacerbations were chosen as the
      outcome assessment criteria. The primary analyses were conducted with a Bayesian
      Markov chain Monte Carlo method. RESULTS: Most of the ICS/LABA combinations
      reduced moderate-to-severe exacerbations as compared with placebo and LABA, but
      none of them reduced severe exacerbations. However, many studies excluded
      patients receiving long-term oxygen therapy. Moderate-dose ICS was as effective
      as high-dose ICS in reducing exacerbations when combined with LABA. CONCLUSION:
      ICS/LABA combinations had a class effect with regard to the prevention of COPD
      exacerbations. Moderate-dose ICS/LABA combination therapy would be sufficient for
      COPD patients when indicated. The efficacy of ICS/LABA combination therapy
      appeared modest and had no impact in reducing severe exacerbations. Further
      studies are needed to evaluate the efficacy of ICS/LABA combination therapy in
      severely affected COPD patients requiring long-term oxygen therapy.

PMID- 24872686
TI  - An ensemble method approach to investigate kinase-specific phosphorylation sites.
AB  - Protein phosphorylation is one of the most significant and well-studied post
      translational modifications, and it plays an important role in various cellular
      processes. It has made a considerable impact in understanding the protein
      functions which are involved in revealing signal transductions and various
      diseases. The identification of kinase-specific phosphorylation sites has an
      important role in elucidating the mechanism of phosphorylation; however,
      experimental techniques for identifying phosphorylation sites are labor intensive
      and expensive. An exponentially increasing number of protein sequences generated
      by various laboratories across the globe require computer-aided procedures for
      reliably and quickly identifying the phosphorylation sites, opening a new horizon
      for in silico analysis. In this regard, we have introduced a novel ensemble
      method where we have selected three classifiers (least square support vector
      machine, multilayer perceptron, and k-Nearest Neighbor) and three different
      feature encoding parameters (dipeptide composition, physicochemical properties of
      amino acids, and protein-protein similarity score). Each of these classifiers is
      trained on each of the three different parameter systems. The final results of
      the ensemble method are obtained by fusing the results of all the classifiers by
      a weighted voting algorithm. Extensive experiments reveal that our proposed
      method can successfully predict phosphorylation sites in a kinase-specific manner
      and performs significantly better when compared with other existing
      phosphorylation site prediction methods. 

PMID- 24872689
TI  - Characterization of rice bran wax policosanol and its nanoemulsion formulation.
AB  - Policosanol, a mixture of long-chain alcohols found in animal and plant waxes,
      has several biological effects; however, it has a bioavailability of less than
      10%. Therefore, there is a need to improve its bioavailability, and one of the
      ways of doing this is by nanoemulsion formulation. Different droplet size
      distributions are usually achieved when emulsions are formed, which solely
      depends on the preparation method used. Mostly, emulsions are intended for better
      delivery with maintenance of the characteristics and properties of the leading
      components. In this study, policosanol was extracted from rice bran wax, its
      composition was determined by gas chromatography mass spectrophotometry,
      nanoemulsion was made, and the physical stability characteristics were
      determined. The results showed that policosanol nanoemulsion has a nanosize
      particle distribution below 100 nm (92.56-94.52 nm), with optimum charge
      distribution (-55.8 to -45.12 mV), pH (6.79-6.92) and refractive index (1.50);
      these were monitored and found to be stable for 8 weeks. The stability of
      policosanol nanoemulsion confers the potential to withstand long storage times. 

PMID- 24872687
TI  - Current approaches to enhance CNS delivery of drugs across the brain barriers.
AB  - Although many agents have therapeutic potentials for central nervous system (CNS)
      diseases, few of these agents have been clinically used because of the brain
      barriers. As the protective barrier of the CNS, the blood-brain barrier and the
      blood-cerebrospinal fluid barrier maintain the brain microenvironment, neuronal
      activity, and proper functioning of the CNS. Different strategies for efficient
      CNS delivery have been studied. This article reviews the current approaches to
      open or facilitate penetration across these barriers for enhanced drug delivery
      to the CNS. These approaches are summarized into three broad categories:
      noninvasive, invasive, and miscellaneous techniques. The progresses made using
      these approaches are reviewed, and the associated mechanisms and problems are
      discussed. 

PMID- 24872691
TI  - Polymersomes containing quantum dots for cellular imaging.
AB  - Quantum dots (QDs) are highly fluorescent and stable probes for cellular and
      molecular imaging. However, poor intracellular delivery, stability, and toxicity
      of QDs in biological compartments hamper their use in cellular imaging. To
      overcome these limitations, we developed a simple and effective method to load
      QDs into polymersomes (Ps) made of poly(dimethylsiloxane)-poly(2-methyloxazoline)
      (PDMS-PMOXA) diblock copolymers without compromising the characteristics of the
      QDs. These Ps showed no cellular toxicity and QDs were successfully incorporated
      into the aqueous compartment of the Ps as confirmed by transmission electron
      microscopy, fluorescence spectroscopy, and fluorescence correlation spectroscopy.
      Ps containing QDs showed colloidal stability over a period of 6 weeks if stored
      in phosphate-buffered saline (PBS) at physiological pH (7.4). Efficient
      intracellular delivery of Ps containing QDs was achieved in human liver carcinoma
      cells (HepG2) and was visualized by confocal laser scanning microscopy (CLSM). Ps
      containing QDs showed a time- and concentration-dependent uptake in HepG2 cells
      and exhibited better intracellular stability than liposomes. Our results suggest
      that Ps containing QDs can be used as nanoprobes for cellular imaging. 

PMID- 24872690
TI  - Nanometer-scale siRNA carriers incorporating peptidomimetic oligomers: physical
      characterization and biological activity.
AB  - Synthetic short interfering RNA (siRNA) oligonucleotides can trigger the RNA
      interference pathway and lead to selective gene silencing. Despite considerable
      enthusiasm and investment, formidable challenges remain that may deter
      translating this breakthrough discovery into clinical applications. In
      particular, the development of efficient, nontoxic, nonimmunogenic methods for
      delivering siRNA in vivo has proven to be exceptionally challenging. Thorough
      analysis of the relationship between the structure and function of siRNA carrier
      systems, both in isolation and in complex with RNA, will facilitate the design of
      efficient nonviral siRNA delivery vehicles. In this study, we explore the
      relationship between the physicochemical characteristics and the biological
      activity of "lipitoid" compounds as potent siRNA delivery vehicles. Lipitoids are
      cationic peptidomimetic oligomers incorporating a peptoid and a phospholipid
      moiety. Lipitoids can associate with siRNA oligonucleotides and self-assemble
      into spherical lipitoid-based nanoparticles (LNPs), with dimensions that are
      dependent upon the medium and the stoichiometric ratio between the cationic
      monomers of the lipitoid and anionic siRNA oligonucleotides. The morphology, gene
      silencing efficiency, and cytotoxicity of the siRNA-loaded LNPs are similarly
      sensitive to the stoichiometry of the complexes. The medium in which the LNPs are
      formed affects the assembled cargo particles' characteristics such as particle
      size, transfection efficiency, and stability. Formation of the LNPs in the
      biological, serum-free medium OptiMEM resulted in LNPs an order of magnitude
      larger than LNPs formed in water, and were twice as efficient in siRNA
      transfection compared to LNPs formed in water. Inhibitor studies were conducted
      to elucidate the efficiency of lysosomal escape and the uptake mechanism of the
      siRNA-loaded LNPs. Our results suggest that these lipitoid-based, siRNA-loaded
      spherical LNPs are internalized through a lipid raft-dependent and dynamin
      mediated pathway, circumventing endosomal and lysosomal encapsulation. The
      lipitoid-siRNA nanospheres proved to be suitable platforms for investigating the
      critical parameters determining the efficiency of transfection agents, revealing
      the necessity for conducting characterization studies in biological media. The
      investigation of the LNP internalization pathway points to an alternative uptake
      route that bypasses the lysosome, explaining the surprisingly high efficiency of
      LNPs and suggesting that the uptake mechanism should be probed rather than
      assumed for the next generation of rationally designed transfection agents. 

PMID- 24872692
TI  - Effective mucoadhesive liposomal delivery system for risedronate: preparation and
      in vitro/in vivo characterization.
AB  - In this work, we aimed to develop chitosan-coated mucoadhesive liposomes
      containing risedronate to improve intestinal drug absorption. Liposomes
      containing risedronate were prepared with 1,2-distearoryl-sn-glycero-3
      phosphocholine and distearoryl-sn-glycero-3-[phospho-rac-(1-glycerol)] using the
      freeze-drying method, with subsequent coating of the anionic surfaces of the
      liposomes with chitosan. The in vitro characteristics of the chitosan-coated
      liposomes were investigated, including their stability, mucoadhesiveness, and
      Caco-2 cell permeability. This formulation was stable in simulated gastric and
      intestinal fluids, with the percentage of drug remaining in the liposomes being
      more than 90% after 24 hours of incubation. Chitosan-coated liposomes also showed
      strong mucoadhesive properties, implying potential electrostatic interaction with
      the mucous layer in the gastrointestinal tract. Compared with the untreated drug,
      chitosan-coated liposomes significantly enhanced the cellular uptake of
      risedronate, resulting in an approximately 2.1-2.6-fold increase in Caco-2 cells.
      Further, the chitosan-coated liposomes increased the oral exposure of risedronate
      by three-fold in rats. Taken together, the results of this study suggest that
      chitosan-coated liposomes containing risedronate should be effective for
      improving the bioavailability of risedronate. 

PMID- 24872694
TI  - Oxidative nanopatterning of titanium generates mesoporous surfaces with
      antimicrobial properties.
AB  - Mesoporous surfaces generated by oxidative nanopatterning have the capacity to
      selectively regulate cell behavior, but their impact on microorganisms has not
      yet been explored. The main objective of this study was to test the effects of
      such surfaces on the adherence of two common bacteria and one yeast strain that
      are responsible for nosocomial infections in clinical settings and biomedical
      applications. In addition, because surface characteristics are known to affect
      bacterial adhesion, we further characterized the physicochemical properties of
      the mesoporous surfaces. Focused ion beam (FIB) was used to generate ultrathin
      sections for elemental analysis by energy-dispersive X-ray spectroscopy (EDS),
      nanobeam electron diffraction (NBED), and high-angle annular dark field (HAADF)
      scanning transmission electron microscopy (STEM) imaging. The adherence of
      Staphylococcus aureus, Escherichia coli and Candida albicans onto titanium disks
      with mesoporous and polished surfaces was compared. Disks with the two surfaces
      side-by-side were also used for direct visual comparison. Qualitative and
      quantitative results from this study indicate that bacterial adhesion is
      significantly hindered by the mesoporous surface. In addition, we provide
      evidence that it alters structural parameters of C. albicans that determine its
      invasiveness potential, suggesting that microorganisms can sense and respond to
      the mesoporous surface. Our findings demonstrate the efficiency of a simple
      chemical oxidative treatment in generating nanotextured surfaces with
      antimicrobial capacity with potential applications in the implant manufacturing
      industry and hospital setting. 

PMID- 24872693
TI  - Self-assembled micelles of novel amphiphilic copolymer cholesterol-coupled F68
      containing cabazitaxel as a drug delivery system.
AB  - Despite being one of the most promising amphiphilic block copolymers, use of
      Pluronic F68 in drug delivery is limited due to its high critical micelle
      concentration (CMC). In this study, we developed a novel F68 derivative,
      cholesterol-coupled F68 (F68-CHMC). This new derivative has a CMC of 10 MUg/mL,
      which is 400-fold lower than that of F68. The drug-loading capacity of F68-CHMC
      was investigated by encapsulating cabazitaxel, a novel antitumor drug. Drug
      loaded micelles were fabricated by a self-assembly method with simple dilution.
      The optimum particle size of the micelles was 17.5+/-2.1 nm, with an entrapment
      efficiency of 98.1% and a drug loading efficiency of 3.16%. In vitro release
      studies demonstrated that cabazitaxel-loaded F68-CHMC micelles had delayed and
      sustained-release properties. A cytotoxicity assay of S180 cells showed that
      blank F68-CHMC was noncytotoxic with a cell viability of nearly 100%, even at a
      concentration of 1,000 MUg/mL. The IC50 revealed that cabazitaxel-loaded F68-CHMC
      micelles were more cytotoxic than Tween 80-based cabazitaxel solution and free
      cabazitaxel. In vivo antitumor activity against S180 cells also indicated better
      tumor inhibition by the micelles (79.2%) than by Tween 80 solution (56.2%,
      P<0.05). Based on these results, we conclude that the F68-CHMC copolymer may be a
      potential nanocarrier to improve the solubility and biological activity of
      cabazitaxel and other hydrophobic drugs. 

PMID- 24872695
TI  - Enhanced bioavailability of apigenin via preparation of a carbon nanopowder solid
      dispersion.
AB  - In this study, a novel carbon nanopowder (CNP) drug carrier was developed to
      improve the oral bioavailability of apigenin (AP). Solid dispersions (SDs) of AP
      with CNP were prepared, and their in vitro drug release and in vivo performance
      were evaluated. The physicochemical properties of the formulations were examined
      by differential scanning calorimetry, X-ray diffraction, and scanning electron
      microscopy. Drug release profiles showed that AP dissolution from the CNP-AP
      system (weight ratio, 6:1) after 60 minutes improved by 275% compared with that
      of pure AP. Moreover, the pharmacokinetic analysis of SD formulations in rats
      showed that the AP area under the curve0-t value was 1.83 times higher for the
      CNP-AP system than for pure AP, indicating that its bioavailability was
      significantly improved. In addition, compared with pure AP, SDs had a
      significantly higher peak and shorter time to peak. Preliminary intestinal
      toxicity tests indicated that there was no significant difference in the tissues
      of the rats treated with the CNP-AP system, rats treated with the CNP alone, and
      controls. In conclusion, CNP-based SDs could be used for enhancing the
      bioavailability of poorly water-soluble drugs while also improving drug safety. 

PMID- 24872696
TI  - Electrospun gelatin/PCL and collagen/PLCL scaffolds for vascular tissue
      engineering.
AB  - Electrospun hybrid nanofibers prepared using combinations of natural and
      synthetic polymers have been widely investigated in cardiovascular tissue
      engineering. In this study, electrospun gelatin/polycaprolactone (PCL) and
      collagen/poly(l-lactic acid-co-epsilon-caprolactone) (PLCL) scaffolds were
      successfully produced. Scanning electron micrographs showed that fibers of both
      membranes were smooth and homogeneous. Water contact angle measurements further
      demonstrated that both scaffolds were hydrophilic. To determine cell attachment
      and migration on the scaffolds, both hybrid scaffolds were seeded with human
      umbilical arterial smooth muscle cells. Scanning electron micrographs and MTT
      assays showed that the cells grew and proliferated well on both hybrid scaffolds.
      Gross observation of the transplanted scaffolds revealed that the engineered
      collagen/PLCL scaffolds were smoother and brighter than the gelatin/PCL
      scaffolds. Hematoxylin and eosin staining showed that the engineered blood
      vessels constructed by collagen/PLCL electrospun membranes formed relatively
      homogenous vessel-like tissues. Interestingly, Young's modulus for the engineered
      collagen/PLCL scaffolds was greater than for the gelatin/PCL scaffolds. Together,
      these results indicate that nanofibrous collagen/PLCL membranes with favorable
      mechanical and biological properties may be a desirable scaffold for vascular
      tissue engineering. 

PMID- 24872698
TI  - Emerging nanotechnology approaches in tissue engineering and regenerative
      medicine.

PMID- 24872697
TI  - Enhancement of radiotherapy efficacy by miR-200c-loaded gelatinase-stimuli PEG
      Pep-PCL nanoparticles in gastric cancer cells.
AB  - Radiotherapy is the main locoregional control modality for many types of
      unresectable tumors, including gastric cancer. However, many patients fail
      radiotherapy due to intrinsic radioresistance of cancer cells, which has been
      found to be strongly associated with cancer stem cell (CSC)-like properties. In
      this study, we developed a nanoparticle formulation to deliver miR-200c, which is
      reported to inhibit CSC-like properties, and then evaluated its potential
      activity as a radiosensitizer. miR-200c nanoparticles significantly augmented
      radiosensitivity in three gastric cancer cell lines (sensitization enhancement
      ratio 1.13-1.25), but only slightly in GES-1 cells (1.06). In addition to
      radioenhancement, miR-200c nanoparticles reduced the expression of CD44, a
      putative CSC marker, and the percentage of CD44(+) BGC823 cells. Meanwhile, other
      CSC-like properties, including invasiveness and resistance to apoptosis, could be
      suppressed by miR-200c nanoparticles. CSC-associated radioresistance mechanisms,
      involving reactive oxygen species levels and DNA repair capacity, were also
      attenuated. We have demonstrated that miR-200c nanoparticles are an effective
      radiosensitizer in gastric cancer cells and induce little radiosensitization in
      normal cells, which suggests that they are as a promising candidate for further
      preclinical and clinical evaluation. 

PMID- 24872699
TI  - Nanotechnology and picotechnology to increase tissue growth: a summary of in vivo
      studies.
AB  - The aim of tissue engineering is to develop functional substitutes for damaged
      tissues or malfunctioning organs. Since only nanomaterials can mimic the surface
      properties (ie, roughness) of natural tissues and have tunable properties (such
      as mechanical, magnetic, electrical, optical, and other properties), they are
      good candidates for increasing tissue growth, minimizing inflammation, and
      inhibiting infection. Recently, the use of nanomaterials in various tissue
      engineering applications has demonstrated improved tissue growth compared to what
      has been achieved until today with our conventional micron structured materials.
      This short report paper will summarize some of the more relevant advancements
      nanomaterials have made in regenerative medicine, specifically improving bone and
      bladder tissue growth. Moreover, this short report paper will also address the
      continued potential risks and toxicity concerns, which need to be accurately
      addressed by the use of nanomaterials. Lastly, this paper will emphasize a new
      field, picotechnology, in which researchers are altering electron distributions
      around atoms to promote surface energy to achieve similar increased tissue
      growth, decreased inflammation, and inhibited infection without potential
      nanomaterial toxicity concerns. 

PMID- 24872700
TI  - Enhanced MIN-6 beta cell survival and function on a nitric oxide-releasing
      peptide amphiphile nanomatrix.
AB  - Innovative biomaterial strategies are required to improve islet cell retention,
      viability, and functionality, and thereby obtain clinically successful outcomes
      from pancreatic islet cell transplantation. To address this need, we have
      developed a peptide amphiphile-based nanomatrix that incorporates multifunctional
      bioactive cues and sustained release of nitric oxide. The goal of this study was
      to evaluate the effect of this peptide amphiphile nanomatrix on the viability and
      functionality of MIN-6 islet cells. Additionally, this study provides insight
      into the role of nitric oxide in islet cell biology, given that conventional
      nitric oxide donors are unable to release nitric oxide in a controlled, sustained
      manner, leading to ambiguous results. It was hypothesized that controlled nitric
      oxide release in synergy with multifunctional bioactive cues would promote islet
      cell viability and functionality. Nitric oxide-releasing peptide amphiphile
      nanomatrices within the range of 16.25 MUmol to 130 MUmol were used to analyze
      MIN-6 cell behavior. Both 32.5 MUmol and 65 MUmol peptide amphiphiles showed
      improved MIN-6 functionality in response to glucose over a 7-day time period, and
      the elevated functionality was correlated with both PDX-1 and insulin gene
      expression. Our results demonstrate that nitric oxide has a beneficial effect on
      MIN-6 cells in a concentration-dependent manner. 

PMID- 24872701
TI  - Substrates coated with silver nanoparticles as a neuronal regenerative material.
AB  - Much effort has been devoted to the design of effective biomaterials for nerve
      regeneration. Here, we report the novel use of silver nanoparticles (AgNPs) as
      regenerative agents to promote neuronal growth. We grew neuroblastoma cells on
      surfaces coated with AgNPs and studied the effect on the development of the
      neurites during the initiation and the elongation growth phases. We find that the
      AgNPs function as favorable anchoring sites, and the growth on the AgNP-coated
      substrates leads to a significantly enhanced neurite outgrowth. Cells grown on
      substrates coated with AgNPs have initiated three times more neurites than cells
      grown on uncoated substrates, and two times more than cells grown on substrates
      sputtered with a plain homogenous layer of silver. The growth of neurites on
      AgNPs in the elongation phase was enhanced as well. A comparison with substrates
      coated with gold nanoparticles (AuNPs) and zinc oxide nanoparticles (ZnONPs)
      demonstrated a clear silver material-driven promoting effect, in addition to the
      nanotopography. The growth on substrates coated with AgNPs has led to a
      significantly higher number of initiating neurites when compared to substrates
      coated with AuNPs or ZnONPs. All nanoparticle-coated substrates affected and
      promoted the elongation of neurites, with a significant positive maximal effect
      for the AgNPs. Our results, combined with the well-known antibacterial effect of
      AgNPs, suggest the use of AgNPs as an attractive nanomaterial - with dual
      activity - for neuronal repair studies. 

PMID- 24872702
TI  - Fabrication and characterization of anisotropic nanofiber scaffolds for advanced
      drug delivery systems.
AB  - Stimuli-responsive, polymer-based nanostructures with anisotropic compartments
      are of great interest as advanced materials because they are capable of switching
      their shape via environmentally-triggered conformational changes, while
      maintaining discrete compartments. In this study, a new class of stimuli
      responsive, anisotropic nanofiber scaffolds with physically and chemically
      distinct compartments was prepared via electrohydrodynamic cojetting with side-by
      side needle geometry. These nanofibers have a thermally responsive, physically
      crosslinked compartment, and a chemically-crosslinked compartment at the
      nanoscale. The thermally responsive compartment is composed of physically
      crosslinkable poly(N-isopropylacrylamide) poly(NIPAM) copolymers, and poly(NIPAM
      co-stearyl acrylate) poly(NIPAM-co-SA), while the thermally-unresponsive
      compartment is composed of polyethylene glycol dimethacrylates. The two distinct
      compartments were physically crosslinked by the hydrophobic interaction of the
      stearyl chains of poly(NIPAM-co-SA) or chemically stabilized via ultraviolet
      irradiation, and were swollen in physiologically relevant buffers due to their
      hydrophilic polymer networks. Bicompartmental nanofibers with the physically
      crosslinked network of the poly(NIPAM-co-SA) compartment showed a thermally
      triggered shape change due to thermally-induced aggregation of poly(NIPAM-co-SA).
      Furthermore, when bovine serum albumin and dexamethasone phosphate were
      separately loaded into each compartment, the bicompartmental nanofibers with
      anisotropic actuation exhibited decoupled, controlled release profiles of both
      drugs in response to a temperature. A new class of multicompartmental nanofibers
      could be useful for advanced nanofiber scaffolds with two or more drugs released
      with different kinetics in response to environmental stimuli. 

PMID- 24872703
TI  - Endocytosis and exocytosis of nanoparticles in mammalian cells.
AB  - Engineered nanoparticles that can be injected into the human body hold tremendous
      potential to detect and treat complex diseases. Understanding of the endocytosis
      and exocytosis mechanisms of nanoparticles is essential for safe and efficient
      therapeutic application. In particular, exocytosis is of significance in the
      removal of nanoparticles with drugs and contrast agents from the body, while
      endocytosis is of great importance for the targeting of nanoparticles in disease
      sites. Here, we review the recent research on the endocytosis and exocytosis of
      functionalized nanoparticles based on various sizes, shapes, and surface
      chemistries. We believe that this review contributes to the design of safe
      nanoparticles that can efficiently enter and leave human cells and tissues. 

PMID- 24872704
TI  - Novel interfaces for light directed neuronal stimulation: advances and
      challenges.
AB  - Light activation of neurons is a growing field with applications ranging from
      basic investigation of neuronal systems to the development of new therapeutic
      methods such as artificial retina. Many recent studies currently explore novel
      methods for optical stimulation with temporal and spatial precision. Novel
      materials in particular provide an opportunity to enhance contemporary
      approaches. Here we review recent advances towards light directed interfaces for
      neuronal stimulation, focusing on state-of-the-art nanoengineered devices. In
      particular, we highlight challenges and prospects towards improved retinal
      prostheses. 

PMID- 24872706
TI  - Delivery of bone morphogenetic protein-2 and substance P using graphene oxide for
      bone regeneration.
AB  - In this study, we demonstrate that graphene oxide (GO) can be used for the
      delivery of bone morphogenetic protein-2 (BMP-2) and substance P (SP), and that
      this delivery promotes bone formation on titanium (Ti) implants that are coated
      with GO. GO coating on Ti substrate enabled a sustained release of BMP-2. BMP-2
      delivery using GO-coated Ti exhibited a higher alkaline phosphatase activity in
      bone-forming cells in vitro compared with bare Ti. SP, which is known to recruit
      mesenchymal stem cells (MSCs), was co-delivered using Ti or GO-coated Ti to
      further promote bone formation. SP induced the migration of MSCs in vitro. The
      dual delivery of BMP-2 and SP using GO-coated Ti showed the greatest new bone
      formation on Ti implanted in the mouse calvaria compared with other groups. This
      approach may be useful to improve osteointegration of Ti in dental or orthopedic
      implants. 

PMID- 24872707
TI  - The taming of the cell: shape-memory nanopatterns direct cell orientation.
AB  - We report here that the direction of aligned cells on nanopatterns can be tuned
      to a perpendicular direction without use of any biochemical reagents. This was
      enabled by shape-memory activation of nanopatterns that transition from a
      memorized temporal pattern to the original permanent pattern by heating. The
      thermally induced shape-memory nanopatterns were prepared by chemically
      crosslinking semi-crystalline poly(epsilon-caprolactone) (PCL) in a mold to show
      shape-memory effects over its melting temperature (Tm = 33 degrees C). Permanent
      surface patterns were first generated by crosslinking the PCL macromonomers in a
      mold, and temporary surface patterns were then embossed onto the permanent
      patterns. The temporary surface patterns could be easily triggered to transition
      quickly to the permanent surface patterns by a 37 degrees C heat treatment, while
      surface wettability was independent of temperature. To investigate the role of
      dynamic and reversible surface nanopatterns on cell alignment on the PCL films
      before and after a topographic transition, NIH 3T3 fibroblasts were seeded on
      fibronectin-coated PCL films with a temporary grooved topography (grooves with a
      height of 300 nm and width of 2 MUm were spaced 9 MUm apart). Interestingly,
      cells did not change their direction immediately after the surface transition.
      However, cell alignment was gradually lost with time, and finally cells realigned
      parallel to the permanent grooves that emerged. The addition of a cytoskeletal
      inhibitor prevented realignment. These results clearly indicate that cells can
      sense dynamic changes in the surrounding environments and spontaneously adapt to
      a new environment by remodeling their cytoskeleton. These findings will serve as
      the basis for new development of spatiotemporal tunable materials to direct cell
      fate. 

PMID- 24872705
TI  - Stealth nanotubes: strategies of shielding carbon nanotubes to evade opsonization
      and improve biodistribution.
AB  - Carbon nanotubes (CNTs) have recently been in the limelight for their potential
      role in disease diagnostics and therapeutics, as well as in tissue engineering.
      Before these medical applications can be realized, there is a need to address
      issues like opsonization, phagocytosis by macrophages, and sequestration to the
      liver and spleen for eventual elimination from the body; along with equally
      important issues such as aqueous solubility, dispersion, biocompatibility, and
      biofunctionalization. CNTs have not been shown to be able to evade such
      biological obstacles, which include their nonspecific attachments to cells and
      other biological components in the bloodstream, before reaching target tissues
      and cells in vivo. This will eventually determine their longevity in circulation
      and clearance rate from the body. This review article discusses the current
      status, challenges, practical strategies, and implementations of coating CNTs
      with biocompatible and opsonin-resistant moieties, rendering CNTs transparent to
      opsonins and deceiving the innate immune response to make believe that the CNTs
      are not foreign. A holistic approach to the development of such "stealth" CNTs is
      presented, which encompasses not only several biophysicochemical factors that are
      not limited to surface treatment of CNTs, but also extraneous biological factors
      such as the protein corona formation that inevitably controls the in vivo fate of
      the particles. This review also discusses the present and potential applications,
      along with the future directions, of CNTs and their hybrid-based nanotheranostic
      agents for multiplex, multimodal molecular imaging and therapy, as well as in
      other applications, such as drug delivery and tissue engineering. 

PMID- 24872708
TI  - A glimpse into the interactions of cells in a microenvironment: the modulation of
      T cells by mesenchymal stem cells.
AB  - Mesenchymal stem cells (MSCs) have been thought to hold potential as a mode of
      therapy for immuno-related pathologies, particularly for autoimmune diseases.
      Despite their potential, the interaction between MSCs and T cells, key players in
      the pathophysiology of autoimmune diseases, is not yet well understood, thereby
      preventing further clinical progress. A major obstacle is the highly
      heterogeneous nature of MSCs in vitro. Unfortunately, bulk assays do not provide
      information with regard to cell-cell contributions that may play a critical role
      in the overall cellular response. To address these issues, we investigated the
      interaction between smaller subsets of MSCs and CD4 T cells in a microwell array.
      We demonstrate that MSCs appear capable of modulating the T cell proliferation
      rate in response to persistent cell-cell interactions, and we anticipate the use
      of our microwell array in the classification of subpopulations within MSCs,
      ultimately leading to specific therapeutic interventions. 

PMID- 24872709
TI  - Effect of self-assembled peptide-mesenchymal stem cell complex on the progression
      of osteoarthritis in a rat model.
AB  - PURPOSE: To evaluate the efficacy of mesenchymal stem cells (MSCs) encapsulated
      in self-assembled peptide (SAP) hydrogels in a rat knee model for the prevention
      of osteoarthritis (OA) progression. MATERIALS AND METHODS: Nanostructured KLD-12
      SAPs were used as the injectable hydrogels. Thirty-three Sprague Dawley rats were
      used for the OA model. Ten rats were used for the evaluation of biotin-tagged SAP
      disappearance. Twenty-three rats were divided into four groups: MSC (n=6), SAP
      (n=6), SAP-MSC (n=6), and no treatment (n=5). MSCs, SAPs, and SAP-MSCs were
      injected into the knee joints 3 weeks postsurgery. Histologic examination,
      immunofluorescent staining, measurement of cytokine levels, and micro-computed
      tomography analysis were conducted 6 weeks after injections. Behavioral studies
      were done to establish baseline measurements before treatment, and repeated 3 and
      6 weeks after treatment to measure the efficacy of SAP-MSCs. RESULTS:
      Concentration of biotinylated SAP at week 1 was not significantly different from
      those at week 3 and week 6 (P=0.565). Bone mineral density was significantly
      lower in SAP-MSC groups than controls (P=0.002). Significant differences in
      terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling
      staining between the control group and all other groups were observed. Caspase-8,
      tissue inhibitor of metalloproteinases 1, and matrix metalloproteinase 9 were
      diffusely stained in controls, whereas localized or minimal staining was observed
      in other groups. Modified Mankin scores were significantly lower in the SAP and
      SAP-MSC groups than in controls (P=0.001 and 0.013). Although not statistically
      significant, synovial inflammation scores were lower in the SAP (1.3+/-0.3) and
      SAP-MSC (1.3+/-0.2) groups than in controls (2.6+/-0.2). However, neither the
      cytokine level nor the behavioral score was significantly different between
      groups. CONCLUSION: Injection of SAP-MSC hydrogels showed evidence of
      chondroprotection, as measured by the histologic grading and decreased expression
      of biochemical markers of inflammation and apoptosis. It also lowered subchondral
      bone mineral density, which can be increased by OA. This suggests that the SAP
      MSC complex may have clinical potential to inhibit OA progression.

PMID- 24872711
TI  - Two thymus-related autoimmune disorders: a case report and review of the
      literature.
AB  - Thymoma is the most common tumor in the anterior mediastinum. A 56-year-old man
      presented unremitting and periodic chronic diarrhea of 9 weeks duration, and
      clinical examination revealed a huge nonhomogeneous mass lesion in the right lung
      and leukocytosis. He was treated with CHOP regimen (cyclophosphamide 1,200
      mg/m(2), doxorubicin 50 mg/m(2), vincristine 1.5 mg/m(2), and prednisolone 75
      mg/m(2) * 5 days) based on lung mass computed tomography-guided biopsy, but he
      was reevaluated because neither symptom improved. Surprisingly, celiac disease
      was documented with increased titer of immunoglobulin antibodies to gliadin and
      tissue transglutaminase. Lung mass rebiopsy and thymectomy demonstrated thymoma.
      After surgery, the patient showed aplastic anemia that responded well to
      cyclosporine. At 2-year follow-up, the patient's hematologic status and diarrhea
      were completely recovered and no symptom and/or sign of thymoma recurrence was
      seen. 

PMID- 24872710
TI  - Factors influencing dyslipidemia in statin-treated patients in Lebanon and
      Jordan: results of the Dyslipidemia International Study.
AB  - BACKGROUND: Cardiovascular disease is the leading cause of death and disability
      worldwide. Therefore, as part of the Dyslipidemia International Study (DYSIS), we
      have analyzed the prevalence of lipid abnormalities and risk factors for
      dyslipidemia in statin-treated patients in Lebanon and Jordan. METHODS: This
      cross-sectional, multicenter study enrolled 617 patients at 13 hospitals in
      Lebanon and Jordan. Patients were at least 45 years old and had been treated with
      statins for at least 3 months. Multivariate logistic regression analysis was used
      to determine patient characteristics contributing to dyslipidemia during statin
      therapy. RESULTS: Our findings indicated that 55.9% of statin-treated patients
      (mean age 60.3 years, 47% female) in Lebanon and Jordan did not achieve goal
      levels for low-density lipoprotein cholesterol which were dependent on Systematic
      Coronary Risk Evaluation (SCORE) risk, and 70% of patients (76% men and 63.3% of
      women) were at very high cardiovascular risk. Low-density lipoprotein cholesterol
      goals were not achieved in 67.2% of those with very high cardiovascular risk. The
      most commonly prescribed statin was atorvastatin (44.6%), followed by simvastatin
      (27.7%), rosuvastatin (21.2%), fluvastatin (3.3%), pravastatin (3%), and
      lovastatin (0.2%). Approximately half of the population was treated with a statin
      dose potency of 4, equaling 40 mg of simvastatin. In Lebanon and Jordan, the
      strongest independent associations with low-density lipoprotein cholesterol not
      at goal were current smoking (odds ratio [OR] 1.96; 95% confidence [CI] 1.25
      3.08), diabetes mellitus (OR 2.53; 95% CI 1.70-3.77), and ischemic heart disease
      (OR 2.26; 95% CI 1.45-3.53), while alcohol consumption was associated with
      reduced risk (OR 0.12; 95% CI 0.03-0.57). CONCLUSION: We observed that many
      patients in Lebanon and Jordan experienced persistent dyslipidemia during statin
      treatment, supporting the notion that novel lipid-lowering strategies need to be
      developed. Also, social programs aimed at combating the extremely high rates of
      tobacco use and obesity in Lebanon and Jordan are critical for combating
      cardiovascular disease in these countries.

PMID- 24872712
TI  - Considering the role of radiation therapy for gastrointestinal stromal tumor.
AB  - Gastrointestinal stromal tumors (GISTs) are rare mesenchymal tumors arising in
      the gastrointestinal tract. Over the last decade, the management and prognosis of
      GISTs has changed dramatically with molecular characterization of the c-kit
      mutation and the adoption of targeted systemic therapy. Currently, the standard
      of care for resectable tumors is surgery, followed by adjuvant imatinib for
      tumors at high risk for recurrence. Inoperable or metastatic tumors are treated
      primarily with imatinib. Despite excellent initial response rates, resistance to
      targeted therapy has emerged as a common clinical problem, with relatively few
      therapeutic solutions. While the treatment of GISTs does not commonly include
      radiotherapy, radiation therapy could be a valuable contributing modality.
      Several case reports indicate that radiation can control locally progressive,
      drug-resistant disease. Further study is necessary to define whether radiation
      could potentially prevent or delay the onset of drug resistance, or improve
      outcomes when given in combination with imatinib. 

PMID- 24872714
TI  - Prevalence and pattern of overweight and obesity in three rural communities in
      southwest Nigeria.
AB  - BACKGROUND: Limited data exist on the prevalence of overweight and obesity in the
      Nigerian adult rural population. This study therefore assessed the prevalence and
      pattern of overweight and obesity in adults in three rural communities of the Ife
      North Local Government Area, Nigeria. MATERIALS AND METHODS: A total of 777
      adults between 20 and 90 years of age were recruited into this cross-sectional
      study, which was performed over a 6-month period using a multistage proportional
      stratified random sampling technique. Sociodemographic data and anthropometric
      variables were obtained. RESULTS: A total of 385 (49.5%) men and 395 (50.5%)
      women participated in the study. The mean age and body mass index of the
      participants were 36.3+/-14.3 years and 23.53+/-4.6 kg/m(2), respectively. The
      overall crude prevalence of overweight and obesity in the total population were
      20.8% and 8.4%, respectively. Obesity increased across the age gradient, peaking
      in the 51- to 60-year age-group in men and women. Among the overweight and obese
      subjects (n=227), 70.9% of them were overweight and the remaining 29.1% were
      obese, with class I obesity accounting for 20.7% of these overweight and obese
      subjects. CONCLUSION: The prevalence of overweight and obesity in these
      communities was 20.8% and 8.4% respectively, indicating a trend towards increased
      prevalence. Class I obesity is the most common obesity pattern, and obesity
      increased across the age gradient, peaking in the 51- to 60-year age-group. There
      is a need for regular community education on healthy lifestyles, and regular
      health screening to control the rising prevalence of overweight and obesity, as
      well as to prevent or reduce the risk of obesity comorbidities in these
      communities.

PMID- 24872713
TI  - Clinical response to sunitinib as a multitargeted tyrosine-kinase inhibitor (TKI)
      in solid cancers: a review of clinical trials.
AB  - Angiogenesis is an integral process in carcinogenesis, and molecular inhibitors
      of angiogenic factors are currently being tested as treatments for cancer.
      Sunitinib is an oral multitargeted tyrosine-kinase inhibitor that blocks
      activation through the stem cell-factor receptor (Kit) and platelet-derived
      growth-factor receptor. Sunitinib has shown potent antitumor activity against
      several solid tumors, including renal cell carcinoma, gastrointestinal stromal
      tumors, and neuroendocrine tumors in several Phase II/III trials. Recently,
      sunitinib has been used to treat other solid cancers, such as lung cancer,
      pancreatic cancer, chondrosarcoma, esophageal cancer, bladder cancer, glioma, and
      aggressive fibromatosis, and also showed potential efficacy in progression-free
      survival and overall survival. In this review, we examine the efficacy of
      sunitinib as a molecular-targeted therapy in patients with different types of
      solid cancers. 

PMID- 24872715
TI  - A single center, pilot, double-blinded, randomized, comparative, prospective
      clinical study to evaluate improvements in the structure and function of facial
      skin with tazarotene 0.1% cream alone and in combination with GliSODin((r)) Skin
      Nutrients Advanced Anti-Aging Formula.
AB  - BACKGROUND: Superoxide dismutase (SOD) reduces the reactive oxygen species
      formation associated with oxidative stress. An imbalance between free radicals
      and antioxidants can lead to accelerated aging. GliSODin((r)) Skin Nutrients
      Advanced Anti-Aging Formula (GAAF) is an SOD-containing dietary nutricosmetic
      formulated with other nutraceuticals that promote improvements in the structure
      and function of the skin, including hydration, elasticity, structural integrity,
      and photoaging caused by oxidative stress. Tazarotene cream 0.1% (TAZ) is a
      United States Food and Drug Administration-approved drug indicated for use in the
      mitigation of facial fine wrinkling, facial mottled hyper- and hypopigmentation,
      and benign facial lentigines when taken in conjunction with a comprehensive skin
      care and sun avoidance program. OBJECTIVE: To determine if the antioxidant, anti
      aging, hydrating and skin-rejuvenating properties of GAAF complement the retinoic
      actions of TAZ to improve the structure and function of facial skin. METHOD: A 90
      day comparative study of ten subjects with facial photodamage; daily topical
      application of TAZ was used in combination with three capsules of GAAF (780 mg
      each) or placebo orally, with food, per the randomization allocation. RESULTS:
      After 90 days of treatment, TAZ alone and in combination with GAAF improved fine
      wrinkles (?1.2 versus 2.0), mottled hyperpigmentation (?2.2 versus 2.8) and
      overall photodamage (?1.0 versus 1.8), as well as patient-reported response to
      treatment (?2.0 versus 1.6). At week 12, TAZ/GAAF combination treatment (Group A)
      versus TAZ treatment alone (Group C) was of significant clinical benefit, with
      respect to fine wrinkling (14.7%/41.7%), overall photodamage (15.6%/53.0%), skin
      moisture (19.1%/103.2%), skin elasticity (12.8%/87.7%), and response to treatment
      (8.8%/21.4%). CONCLUSION: The study suggests GAAF in combination with TAZ is safe
      and provides significant clinical benefit with relative improvement in facial
      fine wrinkling, overall photodamage, skin moisture and elasticity.

PMID- 24872717
TI  - The use of drugs in patients who have undergone bariatric surgery.
AB  - According to the World Health Organization, obesity has become an epidemic in the
      21st century affecting around 300 million people of all ages worldwide. Clinical
      treatment modalities for this disease are limited and ineffective when it comes
      to morbidly obese patients (body mass index - the weight in kilograms divided by
      height in meters squared - surpasses 40 kg/m(2)). Therefore, the alternative,
      surgical treatment, is the best option for these patients, namely gastric
      restrictive procedures or an intestinal bypass culminating in a malabsorptive
      syndrome. In the past 20 years, there has been a 70% increase in the number of
      bariatric procedures all over the world. The main pharmacokinetic consequence
      observed in the postoperative period of these individuals is a higher or lower
      absorption of orally administered drugs. 

PMID- 24872718
TI  - Health impact of smoking - an unforgiveable omission in a doctor's repertoire.

PMID- 24872719
TI  - The damage done by the war on opioids: the pendulum has swung too far.

PMID- 24872720
TI  - Preventive analgesia for postoperative pain control: a broader concept.
AB  - Pain from surgical procedures occurs as a consequence of tissue trauma and may
      result in physical, cognitive, and emotional discomfort. Almost a century ago,
      researchers first described a possible relationship between intraoperative tissue
      damage and an intensification of acute pain and long-term postoperative pain, now
      referred to as central sensitization. Nociceptor activation is mediated by
      chemicals that are released in response to cellular or tissue damage. Pre-emptive
      analgesia is an important concept in understanding treatment strategies for
      postoperative analgesia. Pre-emptive analgesia focuses on postoperative pain
      control and the prevention of central sensitization and chronic neuropathic pain
      by providing analgesia administered preoperatively but not after surgical
      incision. Additional research in pre-emptive analgesia is warranted to better
      determine good outcome measurements and a better appreciation with regard to
      treatment optimization. Preventive analgesia reduces postoperative pain and
      consumption of analgesics, and this appears to be the most effective means of
      decreasing postoperative pain. Preventive analgesia, which includes multimodal
      preoperative and postoperative analgesic therapies, results in decreased
      postoperative pain and less postoperative consumption of analgesics. 

PMID- 24872721
TI  - Computed tomography-guided bupivacaine and corticosteroid injection for the
      treatment of symptomatic calcification in the great toe tendon.
AB  - BACKGROUND: Calcification in the great toe tendon is a rare disorder that is
      characterized by the deposition of calcium on degenerative collagen fibrils. CASE
      PRESENTATIONS: IN THIS REPORT, WE PRESENT TWO CASES OF CALCIFIC TENDONITIS: one
      in the adductor hallucis and the other in the flexor hallucis longus tendon. We
      preferred computed tomography-guided steroid injection in our cases because of
      pain unresponsive to conservative treatment. Patients were free of symptoms at
      the follow-up visit, 4 weeks after injection. CONCLUSION: Calcification of the
      hallux tendons is a rare disorder. Treatment of tendonitis consists of
      nonsteroidal anti-inflammatory drugs. Local anesthetic and steroid injection may
      be considered in cases unresponsive to conservative treatment. Because of the
      anatomic location of tendons, injection could be difficult. Computed tomography
      guidance may improve the success rate of injections.

PMID- 24872716
TI  - Current approaches to the management of new-onset ulcerative colitis.
AB  - Ulcerative colitis (UC) is an idiopathic, inflammatory gastrointestinal disease
      of the colon. As a chronic condition, UC follows a relapsing and remitting course
      with medical maintenance during periods of quiescent disease and appropriate
      escalation of therapy during times of flare. Initial treatment strategies must
      not only take into account current clinical presentation (with specific regard
      for extent and severity of disease activity) but must also take into
      consideration treatment options for the long-term. The following review offers an
      approach to new-onset UC with a focus on early treatment strategies. An
      introduction to the disease entity is provided along with an approach to initial
      diagnosis. Stratification of patients based on clinical parameters, disease
      extent, and severity of illness is paramount to determining course of therapy.
      Frequent assessments are required to determine clinical response, and treatment
      intensification may be warranted if expected improvement goals are not
      appropriately reached. Mild-to- moderate UC can be managed with aminosalicylates,
      mesalamine, and topical corticosteroids with oral corticosteroids reserved for
      unresponsive cases. Moderate-to-severe UC generally requires oral or intravenous
      corticosteroids in the short-term with consideration of long-term management
      options such as biologic agents (as initial therapy or in transition from
      steroids) or thiopurines (as bridging therapy). Patients with severe or fulminant
      UC who are recalcitrant to medical therapy or who develop disease complications
      (such as toxic megacolon) should be considered for colectomy. Early surgical
      referral in severe or refractory UC is crucial, and colectomy may be a life
      saving procedure. The authors provide a comprehensive evidence-based approach to
      current treatment options for new-onset UC with discussion of long-term
      therapeutic efficacy and safety, patient-centered perspectives including quality
      of life and medication compliance, and future directions in related inflammatory
      bowel disease care. 

PMID- 24872722
TI  - Potential of prescription registries to capture individual-level use of aspirin
      and other nonsteroidal anti-inflammatory drugs in Denmark: trends in utilization
      1999-2012.
AB  - BACKGROUND: Due to over-the-counter availability, no consensus exists on whether
      adequate information on nonsteroidal anti-inflammatory drug (NSAID) use can be
      obtained from prescription registries. OBJECTIVES: To examine utilization of
      aspirin and nonaspirin NSAIDs in Denmark between 1999 and 2012 and to quantify
      the proportion of total sales that was sold on prescription. METHOD: Based on
      nationwide data from the Danish Serum Institute and the Danish National
      Prescription Registry, we retrieved sales statistics for the Danish primary
      health care sector to calculate 1-year prevalences of prescription users of
      aspirin or nonaspirin NSAIDs, and to estimate the corresponding proportions of
      total sales dispensed on prescription. RESULTS: Both low-dose aspirin and
      nonaspirin NSAIDs were commonly used in the Danish population between 1999 and
      2012, particularly among elderly individuals. The 1-year prevalence of prescribed
      low-dose aspirin increased throughout the study period, notably among men.
      Nonaspirin NSAID use was frequent in all age groups above 15 years and showed a
      female preponderance. Overall, the prevalence of prescribed nonaspirin NSAIDs
      decreased moderately after 2004, but substantial variation according to NSAID
      subtype was observed; ibuprofen use increased, use of all newer selective
      cyclooxygenase-2 inhibitors nearly ceased after 2004, diclofenac use decreased by
      nearly 50% after 2008, and naproxen use remained stable. As of 2012, the
      prescribed proportion of individual-level NSAID sales was 92% for low-dose
      aspirin, 66% for ibuprofen, and 100% for all other NSAIDs. CONCLUSION: The
      potential for identifying NSAID use from prescription registries in Denmark is
      high. Low-dose aspirin and nonaspirin NSAID use varied substantially between 1999
      and 2012. Notably, use of cyclooxygenase-2 inhibitors nearly ceased, use of
      diclofenac decreased markedly, and naproxen use remained unaltered.

PMID- 24872724
TI  - Clinical potential, safety, and tolerability of arbaclofen in the treatment of
      autism spectrum disorder.
AB  - Autism spectrum disorder (ASD) is a behaviorally defined disorder which has
      increased in prevalence over the last two decades. Despite decades of research,
      no effective treatment is currently available. Animal models, as well as other
      lines of evidence, point to abnormalities in the balance of cortical excitation
      to inhibition in individuals with ASD, with this imbalance resulting in an
      overall increase in cortical excitation. To reduce cortical excitatory glutamate
      pathways, arbaclofen, a selective agonist of the gamma aminobutyric acid receptor
      type B, has been developed. This article reviews the evidence for this treatment
      for ASD using a systematic review methodology. Overall, a systematic search of
      the literature revealed 148 relevant references with the majority of these being
      review papers or news items that mentioned the potential promise of arbaclofen.
      Five original studies were identified, four of which used STX209, a form of
      arbaclofen developed by Seaside Therapeutics, Inc., and one which used R
      baclofen. In an animal model, treatment of Fragile X, a genetic disease with ASD
      features, demonstrated a reversal of behavioral, neurological, and
      neuropathological features associated with the disease. One double-blind, placebo
      controlled study treated children and adults with Fragile X. Results from this
      study were promising, with signs of improvement in social function, especially in
      the most severely socially impaired. Two studies, one open-label and one double
      blind, placebo-controlled, were conducted in children, adolescents, and young
      adults with ASD. These studies suggested some improvements in socialization,
      although the effects were limited and may have been driven by individuals with
      ASD that were higher-functioning. These studies and others that have used
      arbaclofen for the treatment of gastroesophageal reflux suggest that arbaclofen
      is safe and well-tolerated. Clearly, further clinical studies are needed in order
      to refine the symptoms and characteristics of children with ASD that are best
      treated with arbaclofen. 

PMID- 24872725
TI  - Does cognitive behavior therapy alter emotion regulation in inpatients with a
      depressive disorder?
AB  - INTRODUCTION: Emotion regulation plays an important role in the development and
      treatment of depression. The present study investigated whether the emotion
      regulation strategies, expressive suppression (ES) and cognitive reappraisal (CR)
      change in the course of cognitive behavior therapy (CBT) of depressive
      inpatients. Furthermore, it also examined whether changes in CR and ES correlated
      with positive treatment outcomes. METHODS: Forty-four inpatients from a
      psychotherapeutic hospital who suffered from a depressive disorder (mean age
      =36.4 years, standard deviation =13.4 years; 63.6% female) filled in the Emotion
      Regulation Questionnaire and the Beck Depression Inventory at admission and
      discharge. To detect changes in emotion regulation, and depression across
      treatment, data were analyzed using multivariate analyses of variance (MANOVA)
      for repeated measures, effect sizes, and Spearman correlations. A P-value of
      <=0.05 was considered statistically significant. RESULTS: Depression severity
      (F[1]=10.42, P=0.003; eta(2) =0.22) and CR (F[1]=4.71, P=0.04; eta(2) =0.11)
      changed significantly across CBT treatment. ES remained virtually stable. Post
      treatment scores of CR were also positively correlated with reduction in
      depressive symptoms across treatment (rho=0.30, P=0.05). CONCLUSION: The results
      suggest that CBT affects emotion regulation in depressive inpatients only for CR
      and that higher post-treatment scores in CR were related to greater reduction in
      depressive symptoms across treatment.

PMID- 24872726
TI  - Power Evaluation of Focused Cluster Tests.
AB  - Many statistical tests have been developed to assess the significance of clusters
      of disease located around known sources of environmental contaminants, also known
      as focused disease clusters. The majority of focused-cluster tests were designed
      to detect a particular spatial pattern of clustering, one in which the disease
      cluster centers around the pollution source and declines in a radial fashion with
      distance. However, other spatial patterns of environmentally related disease
      clusters are likely given that the spatial dispersion patterns of environmental
      contaminants, and thus human exposure, depend on a number of factors (i.e.,
      meteorology and topography). For this study, data were simulated with five
      different spatial patterns of disease clusters, reflecting potential pollutant
      dispersion scenarios: 1) a radial effect decreasing with increasing distance, 2)
      a radial effect with a defined peak and decreasing with distance, 3) a simple
      angular effect, 4) an angular effect decreasing with increasing distance and 5)
      an angular effect with a defined peak and decreasing with distance. The power to
      detect each type of spatially distributed disease cluster was evaluated using
      Stone's Maximum Likelihood Ratio Test, Tango's Focused Test, Bithell's Linear
      Risk Score Test, and variations of the Lawson-Waller Score Test. Study findings
      underscore the importance of considering environmental contaminant dispersion
      patterns, particularly directional effects, with respect to focused-cluster test
      selection in cluster investigations. The effect of extra variation in risk also
      is considered, although its effect is not substantial in terms of the power of
      tests.

PMID- 24872727
TI  - Biogeochemical consequences of an oxygenated intrusion into an anoxic fjord.
AB  - BACKGROUND: This paper is based on the studies of the biogeochemical structure of
      the water column in the anoxic Fjord Hunnbunn (south-eastern Norway) performed in
      2009, 2011 and 2012. This Fjord is an enclosed basin of brackish water separated
      by a narrow and shallow outlet to the sea with a permanently anoxic layer. We
      show how an oxygenated intrusion could lead to both positive and negative effects
      on the ecosystem state in Hunnbunn due to a change in the biogeochemical
      structure. RESULTS: During the stratified periods in 2009 and 2012 the anoxic
      layer amounted to approximately 10% of the total water volume in the Fjord, while
      dissolved oxygen (DO) was present in 80-90% of the water. In the autumn of 2011
      the water chemistry structure observed in Fjord Hunnbunn was clearly affected by
      a recent oxygenated intrusion defined by abnormal salinity patterns. This led to
      a shift of the DO boundary position to shallower depths, resulting in a thicker
      anoxic layer comprising approximately 40% of the total water volume, with DO
      present only in approximately 60% of the water. The oxygenated water intrusions
      led to a twofold decrease of the concentrations of hydrogen sulphide, ammonia,
      phosphate and silicate in the deep layers with a simultaneous increase of these
      nutrients and a decrease of the pH level in the surface layers. The
      concentrations of manganese, iron, and mercury species changed dramatically and
      in particular revealed a significant supply of iron and methylmercury to the
      water column. CONCLUSIONS: Oxic water intrusions into anoxic fjords could lead
      not only to the flushing of the bottom anoxia, but to a dispersal of sulphidic
      and low oxygen conditions to the larger bottom area. The elevation of the
      hydrogen sulphide to the shallower layers (that can be rapidly oxidized) is
      accompanied by the appearance in the subsurface water of methylmercury, which is
      easily accumulated by organisms and can be transported to the surrounding waters,
      affecting the ecosystem over a larger area.

PMID- 24872728
TI  - Telephone follow-up by nurse following total knee arthroplasty - protocol for a
      randomized clinical trial (NCT 01771315).
AB  - BACKGROUND: Due to shorter hospitalization, patients have to take responsibility
      for their rehabilitation period at a very early stage. The objective of this
      trial is to study the effects of two treatment schemes following total knee
      arthroplasty: conventional treatment following discharge from hospital and early
      follow-up by telephone consultations in addition to conventional treatment
      following discharge from hospital. The ultimate aim is to increase the
      effectiveness of the treatment by improving patients' health status, promote self
      efficacy, and reduce the number of acute visits to the orthopaedic outpatient
      clinic during the rehabilitation period. METHOD/DESIGN: The design is a
      randomized un-blinded parallel group clinical trial conducted at the Department
      of Orthopaedic Surgery, Gentofte Hospital, the Capital Region of Denmark. In
      total, 116 patients will be allocated by an external randomization program to 2
      groups: an intervention group following usual treatment after discharge
      supplemented by a nurse managed structured follow-up consultation conducted by
      telephone 4 and 14 days after discharge from hospital and a control group
      following treatment as usual. The consultations are structured by key subjects
      relevant to assess the health status according to the VIPS-model (the Swedish
      acronym for the concepts Well-being, Integrity, Prevention and Safety). The
      content of the consultations can vary according to the patients' individual
      situations and needs. All consultations are conducted by the researcher
      responsible for the trial. The effect is measured 1, 3, 6 and 12 months post
      surgery. The primary outcome is self-reported physical function measured by The
      Western Ontario and McMaster Universities Arthritis Index. Secondary outcomes are
      self-reported health-related quality of life, general self-efficacy and the
      number of acute visits to the orthopaedic outpatient clinic. DISCUSSION: The
      result of this trial is expected to provide new knowledge to support the
      development of targeted and effective follow-up after total knee arthroplasty in
      order to improve the patients' health-related knowledge and skills of being able
      to take actively part in their illness and improve their health status. TRIAL
      REGISTRATION: ClinicalTrials.gov: NCT01771315.

PMID- 24872730
TI  - Valerie Lemaine, MD, MPH, FRCSC and Patricia Simmons, MD.

PMID- 24872731
TI  - The adolescent breast.

PMID- 24872723
TI  - Cryptococcal meningitis: epidemiology and therapeutic options.
AB  - Cryptococcal meningitis causes morbidity and mortality worldwide. The burden of
      disease is greatest in middle- and low-income countries with a high incidence of
      human immunodeficiency virus (HIV) infection. Patients taking immunosuppressive
      drugs and some immunocompetent hosts are also at risk. Treatment of cryptococcal
      meningitis consists of three phases: induction, consolidation, and maintenance.
      Effective induction therapy requires potent fungicidal drugs (amphotericin B and
      flucytosine), which are often unavailable in low-resource, high-endemicity
      settings. As a consequence, mortality is unacceptably high. Wider access to
      effective treatment is urgently required to improve outcomes. For human
      immunodeficiency virus-infected patients, judicious management of asymptomatic
      cryptococcal antigenemia and appropriately timed introduction of antiretroviral
      therapy are important. 

PMID- 24872729
TI  - Protein expression and transcription profiles of three strains of Aeromonas
      salmonicida ssp. salmonicida under normal and iron-limited culture conditions.
AB  - BACKGROUND: Aeromonas salmonicida is an important fish pathogen that produces a
      wide and varied array of virulence factors. Here we used iron deprivation by
      addition of the chelator 2'2-dipyridyl to induce the expression of several such
      virulence factors in three isolates of Aeromonas salmonicida (one avirulent and
      two virulent). By using SDS-PAGE followed by mass spectrometry, we identified
      proteins that appeared differentially expressed under these conditions. The
      differential transcription of the identified gene products were subsequently
      measured by reverse transcription quantitative real-time PCR (RT-qPCR). RESULTS:
      Our initial screening using SDS-PAGE identified five proteins that appeared
      differentially expressed in virulent and avirulent isolates or, within the same
      isolates, between bacteria cultivated under iron-rich or iron-deprived
      conditions. The transcription of the genes coding for these proteins were
      subsequently quantified by RT-qPCR. Results of this analysis demonstrated that
      the gene coding for alkyl hydroperoxide reductase (AhpC), a protein involved in
      oxidative stress response, was transcribed at a higher rate in the virulent
      strain as compared to the avirulent strain. Additionally, it was observed that
      addition of an iron chelator to the culture medium lead to a reduction of the
      transcription levels of the regulatory histone-like nucleoid structuring protein
      (H-NS). This was consistent in all three isolates. On the other hand, the
      transcription levels of the virulence array protein (VapA) and the protein ATP
      synthetase F (ATPF) displayed only limited changes, despite being the dominant
      component of a protein fraction that displayed changes during the preliminary SDS
      PAGE screening. This was true regardless of the culture conditions and of the
      isolates considered. Finally, transcription of the enzyme enolase was upregulated
      in the iron-deprived broths in all isolates. CONCLUSIONS: We identified several
      genes differentially expressed under culture conditions known to lead to the
      overexpression of virulence factors. In addition, we identified alkyl
      hydroperoxide as being overexpressed in the virulent isolates compared to the
      avirulent isolates. The results from this study will contribute to enhance our
      understanding of the virulence of A. salmonicida and may suggest new directions
      for further research.

PMID- 24872732
TI  - Development of the human breast.
AB  - Mammalia are so named based on the presence of the mammary gland in the breast.
      The mammary gland is an epidermal appendage, derived from the apocrine glands.
      The human breast consists of the parenchyma and stroma, originating from
      ectodermal and mesodermal elements, respectively. Development of the human breast
      is distinctive for several reasons. The human breast houses the mammary gland
      that produces and delivers milk through development of an extensive tree-like
      network of branched ducts. It is also characterized by cellular plasticity, with
      extensive remodeling in adulthood, a factor that increases its susceptibility to
      carcinogenesis. Also, breast development occurs in distinct stages via complex
      epithelial-mesenchymal interactions, orchestrated by signaling pathways under the
      regulation of systemic hormones. Congenital and acquired disorders of the breast
      often have a basis in development, making its study essential to understanding
      breast pathology. 

PMID- 24872733
TI  - Preventive care and evaluation of the adolescent with a breast mass.
AB  - Adolescents have little knowledge of preventive breast care or breast screening,
      yet exposures in youth influence the risk of future breast disease.Nipple
      piercing increases the risk of trauma and breast infection. Alcohol consumption,
      smoking, nutrition, obesity, reproductive factors, previous cancer and chest
      radiotherapy, family history of breast cancer or genetic mutation increase the
      risk of breast cancer. Breast cancer is rare in adolescents and currently genetic
      testing is not recommended in those under 18 years, as medical surveillance is
      not usually recommended until around 25 years. Screening measures include
      clinical breast exam every 1 to 3 years, and breast self-awareness in healthy
      women from 20 years; and at least annual breast self examination, with annual
      clinical breast examination, mammography and magnetic resonance imaging in high
      risk patients from 25 years. Breast ultrasound is used in diagnostic evaluation
      of breast masses in adolescents as mammography is less sensitive in young women. 

PMID- 24872735
TI  - Diagnosis and management of fibroadenomas in the adolescent breast.
AB  - Fibroadenomas are benign breast masses that can present a management challenge in
      adolescent populations. Most fibroadenomas may be managed conservatively without
      surgery, but those masses that are symptomatic or increasing in size may require
      surgical excision. In adolescents, the implications of surgical intervention in
      the breast are unclear, and there is little outcomes data. In this article, the
      authors discuss the presentation, diagnosis, and management of fibroadenoma in
      adolescents. Key considerations for physicians in treating these masses in this
      population are reviewed. 

PMID- 24872734
TI  - Management of pediatric and adolescent breast masses.
AB  - Breast masses in children and adolescents are uncommon and most often benign.
      Occasionally, however, they require surgical intervention for lifestyle limiting
      symptoms or malignant potential. These masses are best evaluated with physical
      exam and ultrasound. Breast masses likely to be encountered by the surgeon in the
      pediatric and adolescent population include intraductal papillomas, phyllodes
      tumors, primary breast cancer, and metastatic lesions. Unlike adults, pediatric
      and adolescent breast cancer tends to be of the secretory variety and typically
      have less metastatic potential. However, cases of inflammatory and medullary
      breast cancers have also been reported in girls and appear more aggressive.
      Radiation exposure during breast development is a risk factor to subsequent
      development of breast cancer. Surgical objective for a concerning pediatric and
      adolescent breast mass is complete resection while preserving normal breast
      development, when appropriate. The need for routine axillary dissection for
      malignant cases in children appears unnecessary from the limited data available,
      and the authors favor sentinel lymph node sampling and reserve axillary
      dissection for positive lymph nodes. 

PMID- 24872736
TI  - Uncommon benign breast abnormalities in adolescents.
AB  - The authors discuss benign breast abnormalities in the adolescent breast other
      than fibroadenoma. Although fibroadenoma is the most common benign abnormality in
      the adolescent breast, other diagnoses are possible. The majority of adolescents
      who present with a palpable concern or lump have no discrete abnormality on
      ultrasound and are diagnosed with clinical fibrocystic change and followed up to
      ensure clinical stability. Intraductal papilloma and duct ectasia are two benign
      abnormalities associated with bloody nipple discharge, occurring more rarely in
      adolescents compared with adult women. Breast infections can occur in
      adolescents, including both mastitis and/or abscess, and are treated similarly to
      adults, with drainage and antibiotic coverage for Staphylococcus. When infections
      are due to nipple piercing, other organisms should be suspected. All surgical
      procedures in the developing breast should be performed cautiously, as trauma to
      the undeveloped breast can result in failure of breast development or asymmetry,
      and surgical disruption of subareolar ducts can impair or preclude future
      lactation. 

PMID- 24872738
TI  - Congenital anomalies of the breast.
AB  - Poland syndrome is a combination of chest wall deformity and absent or
      hypoplastic pectoralis muscle and breast associated with shortening and
      brachysyndactyly of the upper limb. Clinical presentation varies widely;
      therefore, reconstructive procedures have to be adapted to the deformity, ranging
      from chest wall stabilization or augmentation, dynamic muscle transfer, nipple
      and areola repositioning, and breast augmentation using prosthesis or autologous
      tissue transfer. Other congenital breast anomalies include supernumerary nipple
      and areola (polythelia) and breast (polymastia), which can generally be found on
      the embryonic mammary ridge. Absence of the nipple, areola (athelia), or the
      breast tissue (amastia) is less frequent. 

PMID- 24872737
TI  - Imaging of the adolescent breast.
AB  - The mainstay of breast imaging in the adolescent is ultrasonography. There is
      occasionally a need for additional imaging, particularly with magnetic resonance
      imaging (MRI). Imaging of the adolescent breast differs substantially from the
      adult in both the imaging modalities utilized and the relative likelihood of
      pathologies encountered. The majority of lesions in the adolescent are benign,
      but the presence of a breast lesion may cause anxiety to patients and their
      families due to the wide awareness of breast malignancy in the adult population.
      It is important to be aware of the imaging modalities available to image the
      adolescent breast to prevent unnecessary radiation exposure while answering the
      clinical question. The current recommendations for adolescent diagnostic and
      screening breast imaging will be reviewed. Benign breast lesions such as
      fibroadenomas, fibrocystic change, pseudoangiomatous stromal hyperplasia,
      gynecomastia, and posttraumatic or infectious lesions with their associated
      imaging findings and management will be outlined. Additionally, review of breast
      malignancies that can affect adolescents will provide the reader with features to
      distinguish benign from malignant processes in the adolescent based on imaging
      findings and clinical presentation. 

PMID- 24872739
TI  - Hypoplastic breast anomalies in the female adolescent breast.
AB  - Hypoplastic breast anomalies remain a reconstructive challenge. In this article,
      the authors review the spectrum of nonsyndromic breast hypoplasia in the
      adolescent girl, namely idiopathic breast hypoplasia and tuberous breast
      deformity. Challenges specific to this population include (1) identifying the
      ideal timing for surgery, (2) choosing the optimal reconstructive method while
      taking into consideration ongoing changes in the female body (e.g., future
      pregnancy), and (3) considering the use of a two-stage reconstructive approach to
      gradually expand the skin envelope. A comprehensive review of surgical techniques
      that address these conditions is provided, taking into account the evolution and
      the most recent advances in surgical techniques. 

PMID- 24872740
TI  - Hyperplastic breast anomalies in the female adolescent breast.
AB  - Macromastia in adolescents is multifactorial and usually idiopathic, associated
      with obesity or hormonal imbalances. Less commonly, it can result from virginal
      or juvenile breast hypertrophy, a rare condition of unknown etiology, where an
      alarmingly rapid breast enlargement occurs during puberty. Breast hypertrophy in
      the adolescent population can have significant long-term medical and
      psychological impacts. Although symptoms can be severe, many plastic surgeons,
      pediatricians, and parents are often reluctant to surgically treat adolescent
      macromastia. However, reduction mammoplasty is a safe and effective treatment and
      may be the only way to alleviate the increased social, psychological, and
      physical strain caused by macromastia in adolescents. 

PMID- 24872741
TI  - Gynecomastia in adolescent males.
AB  - Gynecomastia is defined as an enlargement of the male breast. It is often benign,
      and can be the source of significant embarrassment and psychological distress. A
      general medical history and careful physical examination are essential to
      distinguish normal developmental variants from pathological causes. Treatment is
      geared toward the specific etiology when identified. In the majority of cases of
      pubertal gynecomastia, observation and reassurance are the mainstays of therapy
      as the condition usually resolves naturally. Pharmacological treatment and
      surgery are recommended only in selected cases. 

PMID- 24872742
TI  - Nonsurgical management of fibroadenoma and virginal breast hypertrophy.
AB  - The management and treatment of an adolescent presenting with a fibroadenoma or
      virginal breast hypertrophy can be challenging as there is a paucity of original
      research on these conditions. Although surgical therapies are often discussed as
      first-line therapy in adolescents presenting with a breast mass, it is prudent
      that nonsurgical interventions and medical therapies be considered as initial
      therapy with the goal of maintaining an acceptable cosmetic outcome. 

PMID- 24872743
TI  - Considerations in breast augmentation in the adolescent patient.
AB  - Nearly 320,000 breast augmentations were performed in 2011, with adolescents
      under 18 years of age accounting for 4,830 procedures (1.5%). Breast development
      typically starts at 11 years (range, 8-13 years) and is complete at 15 years
      (range, 11-18 years). This wide age range for physical maturity matches the
      equally wide range of emotional maturity in this patient population.
      Developmental, psychological, and regulatory aspects unique to adolescent breast
      augmentation are reviewed. Self-image and societal influences must be considered,
      including both internal and external motivations for seeking breast augmentation.
      Preoperative assessment and counseling of these patients are discussed. Both
      parental consent and adolescent assent must be considered. Ideal conditions for
      adolescent assent are described. Breast augmentation for purely aesthetic
      purposes should be undertaken with extreme caution as ideal conditions for
      complete assent are rare. Augmentation as a technique for breast balancing in
      cases of significant asymmetry can be helpful. 

PMID- 24872745
TI  - James f. Thornton.

PMID- 24872746
TI  - Nasal soft tissue reconstruction.

PMID- 24872744
TI  - Cosmetic and reconstructive breast surgery in adolescents: psychological,
      ethical, and legal considerations.
AB  - Cosmetic and reconstructive breast surgery has increased in popularity among
      adolescents in the United States. As more adolescents pursue these procedures, an
      understanding of the psychological aspects of these surgeries becomes
      increasingly important for the benefit of both patients and providers. The
      authors review the psychological aspects of cosmetic and reconstructive surgical
      breast procedures as they pertain to adolescents, including augmentation
      mammoplasty, gynecomastia correction, breast reduction, and asymmetry correction.
      They include a discussion of the medicolegal and ethical implications of these
      procedures and recommendations for clinical management. 

PMID- 24872747
TI  - Overview of nasal soft tissue reconstruction: keeping it simple.
AB  - The authors provide an overview of nasal soft tissue reconstruction and of the
      senior author's practice. Nasal soft tissue reconstruction is a challenging
      endeavor as the nose is one of the most prominent and complex facial features. A
      multitude of surgical repair options exist, which can make the decision-making
      process unnecessarily complicated. It is advisable that the reconstructive
      surgeon become facile with a handful of surgical techniques versus trying to
      master many techniques. 

PMID- 24872748
TI  - Full-thickness skin grafting in nasal reconstruction.
AB  - Skin grafting in nasal reconstruction, long used by dermatologists, can provide
      superior results and can well be the "go to" procedure for nasal reconstruction.
      The upper two-thirds of the nose is composed of both flattened, featureless and
      often thin skin that is well recreated with defect-only full-thickness grafting.
      Skin grafting for the lower third of the nose has been practiced for years by
      dermatologists; over the last 4 to 5 years, it has been embraced by plastic
      surgeons. The patient and donor site selection is critical. Meticulous attention
      to graft selection, utilization of a no-touch technique during graft harvest and
      placement of surgical bolsters with through-and-through tacking sutures are
      essential to ensure 100% graft take and a successful aesthetic result. 

PMID- 24872749
TI  - The forehead flap: the gold standard of nasal soft tissue reconstruction.
AB  - The forehead flap is one of the oldest recorded surgical techniques for nasal
      reconstruction. As the gold standard for nasal soft tissue reconstruction, the
      forehead flap provides a reconstructive surgeon with a robust pedicle and large
      amount of tissue to reconstruct almost any defect. Modifications provided by
      masters like Burget and Menick have only increased the utility of this
      exceptional flap. Maintaining an axial pattern, utilizing the pedicle ipsilateral
      to the defect, extending the flap at right angles with caution when extra length
      is needed, using a narrow pedicle, and early subperiosteal dissection are the
      guiding principles for forehead flap reconstruction of the nose. In addition,
      lining defects can be addressed simply and reliably with a folded forehead flap. 

PMID- 24872750
TI  - Expanded uses for the nasolabial flap.
AB  - The nasolabial flap is an excellent choice for use in reconstruction of the nasal
      alar subunit due to its inherent properties that match skin tone and the
      convexity of the nose. Often overlooked as an option to use in nasal
      reconstruction, the nasolabial flap can be very advantageous. Indications for the
      nasolabial flap can be expanded to include reconstruction of the nasal tip,
      dorsum, soft triangle, and partial alar defects. 

PMID- 24872751
TI  - Reconstruction of small soft tissue nasal defects.
AB  - Nasal defect repair has been one of the more challenging areas of reconstructive
      surgery due to the lack of uniform nasal skin thickness and complex contours.
      Currently, algorithms for medium to large nasal soft tissue defects have been
      well defined by various authors. Small defects, arbitrarily defined as 1 cm or
      less, still present significant challenges. In this article, the authors examine
      the options available to repair small soft tissue nasal defects and the
      appropriate situations in which each method is best suited. 

PMID- 24872752
TI  - Repair of combined cheek and nose defects: categorization and utilization.
AB  - Combined cheek and nose soft tissue defects can represent a formidable challenge
      to the reconstructive surgeon. It is important for the surgeon to think of these
      defects as four separate categories: cheek with nasal sidewall, cheek with nasal
      sidewall and exposed bone, cheek with nasal sidewall plus ala, and cheek with
      simple posterior ala defect. This categorization will help the surgeon plan the
      repair and provide a successful aesthetic outcome. There are multiple repair
      options that the surgeon can use, and the surgeon should be facile with all
      types. It is universally agreed that the cheek defect must be repaired prior to
      undertaking the repair of the nasal defect. 

PMID- 24872753
TI  - Avoidance and management of complications in soft tissue facial reconstruction.
AB  - Complications in nasal soft tissue reconstruction are inevitable, and all
      reconstructive surgeons should be comfortable with their management. Patient and
      surgical complications can be minimized with appropriate preoperative planning
      and coordination with the anesthesiologist. When managing undesirable results, it
      is important to realize that most results will improve over time with appropriate
      wound care and dermabrasion. Patience and attentiveness to the patient are the
      most-effective strategies for dealing with poor results. 

PMID- 24872754
TI  - A note on surgical revisions.
AB  - Surgical revisions are inherent in nasal reconstruction. It is of benefit to the
      patient if the surgeon is able to accurately counsel the patient on the sequence
      and expectations prior to embarking on a multistage nasal reconstruction. The
      requirement to "wait a year" is an unnecessary patient burden, but almost all
      results improve with time. 

PMID- 24872756
TI  - David y. Khechoyan, MD.

PMID- 24872755
TI  - A note on anesthesia for mohs nasal defects.
AB  - Patients needing surgical repair after nasal Mohs surgery require immediate
      prescreening by an anesthesiology provider to determine if the patient is a
      candidate for the appropriate anesthetic or is to be delayed for more medical
      evaluation. These patients may need anesthesia anywhere on the spectrum from
      local anesthesia only to general endotracheal anesthesia, and this may affect
      where and when the plastic surgeon can proceed. 

PMID- 24872757
TI  - Orthognathic surgery.

PMID- 24872758
TI  - Orthognathic surgery: general considerations.
AB  - ORTHOGNATHIC SURGERY IS A UNIQUE ENDEAVOR IN FACIAL SURGERY: a patient's
      appearance and occlusal function can be improved significantly, impacting the
      patient's sense of self and well-being. Successful outcomes in modern
      orthognathic surgery rely on close collaboration between the surgeon and the
      orthodontist across all stages of treatment, from preoperative planning to
      finalization of occlusion. Virtual computer planning promotes a more accurate
      analysis of dentofacial deformity and preoperative planning. It is also an
      invaluable aid in providing comprehensive patient education. In this article, the
      author describes the general surgical principles that underlie orthognathic
      surgery, highlighting the sequence of treatment, preoperative analysis of
      dentofacial deformity, surgical execution of the treatment plan, and possible
      complications.

PMID- 24872759
TI  - Orthodontist's Role in Orthognathic Surgery.
AB  - Orthognathic surgery can eliminate severe esthetic and functional deformities and
      be a life-changing event for a patient. An orthodontist's role in orthognathic
      surgery can be divided into several phases: the initial evaluation, presurgical
      orthodontics, surgical planning, and postsurgical orthodontics. At each of these
      phases, collaboration between the orthodontist and the surgeon is critical. The
      ability of an orthodontist and a surgeon to coordinate their efforts during this
      time is what will lead to a successful outcome. 

PMID- 24872760
TI  - Bilateral sagittal split osteotomy.
AB  - The bilateral sagittal split osteotomy is an indispensable tool in the correction
      of dentofacial abnormalities. The technique has been in practice since the late
      1800s, but did not reach widespread acceptance and use until several
      modifications were described in the 1960s and 1970s. Those modifications came
      from a desire to make the procedure safer, more reliable, and more predictable
      with less relapse. Those goals continue to stimulate innovation in the field
      today and have helped the procedure evolve to be a very dependable, consistent
      method of correction of many types of malocclusion. The operative surgeon should
      be well versed in the history, anatomy, technical aspects, and complications of
      the bilateral sagittal split osteotomy to fully understand the procedure and to
      counsel the patient. 

PMID- 24872763
TI  - S. Raja sabapathy.

PMID- 24872761
TI  - LeFort I Osteotomy.
AB  - The LeFort I osteotomy is one of the most commonly used procedures to correct
      midface deformities. It allows for correction in three dimensions including
      advancement, retrusion, elongation, and shortening. It is indicated, often in
      conjunction with mandibular surgery, for class II and III malocclusion, facial
      asymmetry, obstructive sleep apnea, and maxillary atrophy. Before surgery, proper
      orthodontics and surgical planning should be undertaken to ensure adequate
      outcomes. Overall, the surgery is widely used due to its low complication profile
      and reliable long-term results. 

PMID- 24872764
TI  - Replantation.

PMID- 24872762
TI  - Aesthetic alteration of the chin.
AB  - Genioplasty, the alteration of the chin through either osseous manipulation or
      implant augmentation, is an integral component of aesthetic surgery of the face.
      When performed with proper preoperative assessment and technical execution, the
      results can harmonize and restore balance between skeletal, soft tissue, and
      dental components of the lower face. To this end, proper understanding of the
      underlying anatomy and the changes associated with movement of the chin, alone or
      in conjunction with formal orthognathic surgery, is paramount. The author
      presents pertinent points on proper assessment, treatment planning, and a
      description of the surgical technique, and discusses complications and outcomes
      to optimize outcome. 

PMID- 24872765
TI  - Challenges in fingertip replantation.
AB  - Fingertip amputation is a challenging injury to manage. Among various
      reconstructive procedures, replantation results in superior outcome, but is
      seldom considered in many institutions. From the identification of vessel ends to
      reanastomosis of the submillimeter vessels, fingertip's highly specialized
      anatomy requires technical excellence. By addressing these anatomic challenges,
      fingertip replantation can be a routine reconstructive option for microvascular
      surgeons. 

PMID- 24872766
TI  - Challenges in measuring outcomes following digital replantation.
AB  - In the early period of replantation surgery, the emphasis was on digit survival.
      Subsequently, with better microsurgical techniques and instrumentation, the focus
      has shifted to function and in recent years to consideration of cost
      effectiveness. Despite over 40 years of effort in refining digital replantation
      surgery, a rigorous evaluation of the outcomes of digital replantation has not
      been performed. This is because of the many confounding variables that influence
      outcome comparisons. These variables include the mechanism of injury (guillotine,
      crush, avulsion), the injury itself (total, near total, subtotal, partial
      amputation), and the surgical procedure (replantation, revascularization). In
      addition, the traditional outcome measures (two-point discrimination, range of
      motion, grip strength, or the ability to return to work) are reported
      inconsistently and vary widely among publications. All these factors make
      meaningful comparison of outcomes difficult. The recent emphasis on outcome
      research and cost-effectiveness necessitates a rethinking in the way we report
      outcomes of digital replantation. In this article, the authors summarize the
      challenges in assessing outcomes of digital replantation and explain the need to
      measure outcomes using rigorous clinical research designs that incorporate cost
      effectiveness studies in the research protocol. 

PMID- 24872767
TI  - Challenges in replantation of complex amputations.
AB  - Surgical ingenuity has resulted in continuing microsurgical innovation in
      replantation. In this article, the authors define complex amputations as those
      that stretch the boundaries or fall outside traditionally defined indications for
      replantation. They discuss management of difficult situations involving multiple
      digit amputations, multiple-level amputations, prolonged ischemia, and multiple
      trauma. The role of transpositional and ectopic replantation, as well as the
      requirement for secondary procedures in replantation is also discussed. Although
      technically challenging, microsurgical management of complex amputations
      ultimately results in far superior outcomes. 

PMID- 24872768
TI  - Spare-part surgery.
AB  - The authors discuss the use of scavenged tissue for reconstruction of an injured
      limb, also referred to as "spare-part surgery." It forms an important part of
      overall reconstructive strategy. Though some principles can be laid down, there
      is no "textbook" method for the surgeon to follow. Successful application of this
      strategy requires understanding of the concept, accurate judgment, and the
      ability to plan "on-the-spot," as well as knowledge and skill to improvise
      composite flaps from nonsalvageable parts. Requirements for limb reconstruction
      vary from simple solutions such as tissue coverage, which include skin grafts or
      flaps to more complex planning as in functional reconstruction of the hand, where
      the functional importance of individual digits as well as the overall prehensile
      function of the hand needs to be addressed right from the time of primary
      surgery. The incorporation of the concept of spare-part surgery allows the
      surgeon to carry out primary reconstruction of the limb without resorting to
      harvest tissue from other regions of the body. 

PMID- 24872771
TI  - Jesse C. Selber, MD, MPH, FACS.

PMID- 24872769
TI  - Secondary procedures in replantation.
AB  - The success of replantation surgery is not judged by survival of the replanted
      part, but by the functional outcome attained. Hence, primary repair of all
      injured structures is the preferred aim. At times, constraints induced by the
      ischemia time and nature of injury preclude primary repair. In such situations,
      secondary procedures are inevitable. Secondary procedures are also frequently
      required to improve the function and appearance of the replanted extremity. The
      incidence of secondary procedures will vary with the level of replantation and
      the type of patient population. Secondary procedures are difficult because they
      carry risk of injury to the vital neurovascular structures that now lay at
      nonanatomical locations. Nevertheless, when indicated and performed with caution
      they could significantly raise the functional status of the individuals. 

PMID- 24872770
TI  - Technical considerations and outcomes in penile replantation.
AB  - Penile amputations are uncommon injuries, therefore, the management and outcome
      of these patients have been compiled from solitary case studies or short reviews.
      Accidental trauma during circumcision, injury inflicted by a partner following
      marital discord, and genital self-mutilation observed in patients with deep
      psychosis, account for a majority of the presentations. Initially, patients with
      total penile amputations were managed by resuturing the penile structures without
      repairing the vessels. A high incidence of skin and glans necrosis, urethral
      strictures, and a failure of sensory recovery were observed, though the penile
      shaft sometimes survived. Presently, microsurgical replantation has markedly
      improved the results, though issues of skin loss and urethral stricture still
      persist. A series of three patients with penile amputation is presented (complete
      = 2, partial = 1); the technical considerations and outcomes are discussed. 

PMID- 24872772
TI  - Robotics in plastic surgery.

PMID- 24872773
TI  - Robotic microsurgical training and evaluation.
AB  - Robotic surgery has expanded rapidly over the past two decades and is in
      widespread use among the surgical subspecialties. Clinical applications in
      plastic surgery have emerged gradually over the last few years. One of the
      promising applications is robotic-assisted microvascular anastomosis. Here the
      authors first describe a process by which an assessment instrument they developed
      called the Structured Assessment of Robotic Microsurgical Skills (SARMS) was
      validated. The instrument combines the previously validated Structured Assessment
      of Microsurgical Skills (SAMS) with other skill domains in robotic surgery.
      Interrater reliability for the SARMS instrument was excellent for all skill areas
      among four expert, blinded evaluators. They then present a process by which the
      learning curve for robotic-assisted microvascular anastomoses was measured and
      plotted. Ten study participants performed five robotic microanastomoses each that
      were recorded, deidentified and scored. Trends in SARMS scores were plotted. All
      skill areas and overall performance improved significantly for each participant
      over the five microanastomotic sessions, and operative time decreased for all
      participants. The results showed an initial steep ascent in technical skill
      acquisition followed by more gradual improvement, and a steady decrease in
      operative times for the cohort. Participants at all levels of training, ranging
      from minimal microsurgical experience to expert microsurgeons gained proficiency
      over the course of five robotic sessions. 

PMID- 24872774
TI  - Robotic-assisted microsurgery for an elective microsurgical practice.
AB  - Robotic-assisted microsurgery can be utilized for either intracorporal or
      extracorporeal surgical procedures. Three-dimensional high-definition
      magnification, a stable ergonomic platform, elimination of physiologic tremor,
      and motion scaling make the robotic platform attractive for microsurgeons for
      complex procedures. Additionally, robotic assistance enables the microsurgeon to
      take microsurgery to challenging intracorporeal locations in a minimally invasive
      manner. Recent adjunctive technological developments offer the robotic platform
      enhanced optical magnification, improved intraoperative imaging, and more precise
      ablation techniques for microsurgical procedures. The authors present the current
      state-of-the art tools available in the robotic-assisted microsurgical platform. 

PMID- 24872775
TI  - Robotic-assisted latissimus dorsi harvest in delayed-immediate breast
      reconstruction.
AB  - For two-stage, implant-based, delayed-immediate reconstruction of the radiated
      breast, robotic-assisted latissimus dorsi harvest (RALDH) is a good option for
      patients who wish to avoid a traditional latissimus dorsi donor-site incision.
      The purpose of this study was to compare outcomes of RALDH and the traditional
      open technique (TOT) for patients undergoing delayed-immediate breast
      reconstruction following radiation therapy. A retrospective analysis of a
      prospective database of all consecutive patients undergoing latissimus dorsi
      harvest for radiated breast reconstruction between 2009 and 2013 was performed.
      Indications, surgical technique, complications, and outcomes were assessed. One
      hundred forty-six pedicled latissimus dorsi muscle flaps were performed for
      breast reconstruction and 17 were performed robotically during the study period
      (average follow-up 14.6 +/- 7.3 mo). Latissimus dorsi breast reconstruction
      following radiation was performed in 64 patients using TOT and 12 using RALDH.
      Surgical complication rates were 37.5% in TOT versus 16.7% in RALDH (p = 0.31)
      including seroma (8.9% versus 8.3%), infection (14.1 versus 8.3%), delayed wound
      healing (7.8% versus 0), and capsular contracture (4.7% vs. 0). Robotic-assisted
      harvest of the latissimus dorsi muscle is associated with a low complication rate
      and reliable results for delayed reconstruction of the irradiated breast while
      eliminating the need for a donor-site incision. 

PMID- 24872776
TI  - Robotic harvest of the rectus abdominis muscle: principles and clinical
      applications.
AB  - Harvest of the rectus abdominis muscle requires an abdominal incision as well as
      violation of the anterior rectus sheath, creating the potential for significant
      surgical-site morbidity (bulges, hernias, infections, seromas). Laparoscopic or
      endoscopic techniques, although feasible, have not become popular among plastic
      surgeons due to multiple technical shortcomings. Robotic surgery on the other
      hand has an easier learning curve, enhanced precision, tremor elimination, motion
      scaling, high resolution, three-dimensional optics and an intuitive interface. As
      a result of these advantages, robotic surgery has permeated into the plastic
      surgery specialty, assuming a role in the harvest of the latissimus dorsi muscle
      flap and other reconstructive procedures. In this review, the authors discuss its
      applicability in the harvest of the rectus abdominis muscle. 

PMID- 24872777
TI  - Transoral robotic reconstructive surgery.
AB  - Transoral robotic surgery (TORS) has emerged as a technique that allows head and
      neck surgeons to safely resect large and complex oropharyngeal tumors without
      dividing the mandible or performing a lip-split incision. These resections
      provide a reconstructive challenge because the cylinder of the oropharynx remains
      closed and both physical access and visualization of oropharyngeal anatomy is
      severely restricted. Transoral robotic reconstruction (TORRS) of such defects
      allows the reconstructive surgeon to inset free flaps or perform adjacent tissue
      transfer while seeing what the resecting surgeon sees. Early experience with this
      technique has proved feasible and effective. Robotic reconstruction has many
      distinct advantages over conventional surgery, and offers patients a less morbid
      surgical course. In this review, we discuss the clinical applicability of
      transoral robotic surgery in head and neck reconstruction, highlighting the
      benefits and limitations of such an approach, and outlining the guidelines for
      its utilization. 

PMID- 24872778
TI  - Robot-assisted surgery of the shoulder girdle and brachial plexus.
AB  - New developments in the surgery of the brachial plexus include the use of less
      invasive surgical approaches and more precise techniques. The theoretical
      advantages of the use of robotics versus endoscopy are the disappearance of
      physiological tremor, three-dimensional vision, high definition, magnification,
      and superior ergonomics. On a fresh cadaver, a dissection space was created and
      maintained by insufflation of CO2. The supraclavicular brachial plexus was
      dissected using the da Vinci robot (Intuitive Surgical, Sunnyvale, CA). A segment
      of the C5 nerve root was grafted robotically. A series of eight clinical cases of
      nerve damage around the shoulder girdle were operated on using the da Vinci
      robot. The ability to perform successful microneural repair was confirmed in both
      the authors' clinical and experimental studies, but the entire potential of
      robotically assisted microneural surgery was not realized during these initial
      cases because an open incision was still required. Robotic-assisted surgery of
      the shoulder girdle and brachial plexus is still in its early stages. It would be
      ideal to have even finer and more suitable instruments to apply fibrin glue or
      electrostimulation in nerve surgery. Nevertheless, the prospects of minimally
      invasive techniques would allow acute and subacute surgical approach of traumatic
      brachial plexus palsy safely, without significant and cicatricial morbidity. 

PMID- 24872780
TI  - Paying attention to school achievement in childhood absence epilepsy.

PMID- 24872779
TI  - Closing the Major Gap in PNES Research: Finding a Home for a Borderland Disorder.
AB  - Psychogenic nonepileptic seizures (PNES) are events commonly encountered by
      primary care physicians, neurologists, pediatricians, and emergency medicine
      physicians in their practices, yet there continues to be significant variability
      in the way they are evaluated, diagnosed, and treated. Lack of understanding this
      condition and limited data on long-term outcome from current treatment paradigms
      have resulted in an environment with iatrogenic injury, morbidity, and
      significant costs to the patient and healthcare system. This article will review
      the current state of research addressing PNES treatment both in the adult and
      pediatric populations. 

PMID- 24872781
TI  - Childhood absence epilepsy: what is all the distraction about?

PMID- 24872782
TI  - Seizures and epileptiform activity in early Alzheimer disease: how hard should we
      be looking?

PMID- 24872783
TI  - Treating refractory generalized epilepsy with stimulation.

PMID- 24872784
TI  - Sudden unexpected death in the epilepsy monitoring unit.

PMID- 24872785
TI  - "Idiopathic" and "genetic" generalized epilepsies intersect.

PMID- 24872786
TI  - ILAE Classification Redux: Ready for Prime Time?

PMID- 24872788
TI  - Benchmark IV Progressing Nicely: Rational Pharmacotherapy May Address Cognitive
      Decline in Epilepsy.

PMID- 24872789
TI  - The Heat is On: L-type Calcium Channels and Febrile Seizures.

PMID- 24872787
TI  - Untangling the dravet syndrome seizure network: the changing face of a rare
      genetic epilepsy.
AB  - Dravet syndrome (also known as Severe Myoclonic Epilepsy of Infancy) is a rare
      genetic epilepsy syndrome commonly associated with loss-of-function mutations in
      SCN1A, the gene encoding the alpha subunit of the voltage-gated sodium channel
      NaV1.1, resulting in haploinsufficiency. Like other voltage-gated sodium
      channels, NaV1.1 function contributes to the rising phase of the neuronal action
      potential; thus, the observation that loss-of-function mutations in this channel
      gene are associated with seizures has created a paradox for the field. Major work
      has been done to untangle this paradox during the past decade, resulting in the
      development of two distinct hypotheses to explain seizures in Dravet syndrome.
      Here, we review the history of these two hypotheses and speculate as to what the
      history of Dravet syndrome research might tell us about its future. 

PMID- 24872790
TI  - Recording from over 1,000 cells: a new toy in place for epilepsy research?

PMID- 24872791
TI  - Of fish and men.

PMID- 24872792
TI  - An Evidence-Based Look at Misconceptions in the Treatment of Patients with IBS-D.
AB  - Irritable bowel syndrome (IBS) is the most common functional gastrointestinal
      disorder and affects up to 12% to 15% of adults in the United States, with a
      higher prevalence among women and those younger than 50 years. IBS adversely
      impacts quality of life and medical expenditures, with significant costs arising
      from healthcare visits and reduced workplace productivity. Recent studies have
      shown that the adverse effects of IBS are so significant that many patients are
      willing to accept risks of adverse events from effective treatment to gain
      symptom relief. Alosetron is a 5-HT3 receptor antagonist approved by the US Food
      and Drug Administration (FDA) for women with severe diarrhea-predominant IBS that
      has not responded to traditional therapies. Alosetron yields overall improvements
      in IBS symptoms in 51% of patients vs 36% treated with placebo, with efficacy
      continuing undiminished over the course of a 48-week randomized, controlled
      trial. In real-world clinical practice, patients receiving alosetron had
      significant improvements in multiple IBS-related clinical parameters, including
      the new FDA IBS-diarrhea composite endpoint, lower gastrointestinal symptoms,
      fecal incontinence, and quality of life. Ischemic colitis and complications of
      constipation have been rare in occurrence. After nearly a decade of alosetron use
      under the risk management plan, adjudication of ischemic colitis and
      complications of constipation cases indicate that their incidence rates have
      remained low and stable. 

PMID- 24872793
TI  - Extending survival with the use of targeted therapy in the treatment of
      hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide, with an
      increasing incidence projected through 2020. HCC is the third-leading cause of
      cancer-related deaths worldwide. Management of HCC is complicated by the fact
      that these patients also have a cirrhotic or otherwise diseased liver that led to
      the tumorigenesis. To aid in treatment decisions, several staging systems have
      been developed. In the United States, the Barcelona Clinic Liver Cancer (BCLC)
      system has emerged as the predominant system, owing to its concomitant
      consideration of tumor stage, liver function, and physical status, as well as its
      ability to identify patients with early-stage disease who may benefit from
      curative therapies. Surveillance for HCC has gained increasing importance in
      light of several studies demonstrating both clinical and cost benefits. Once HCC
      is detected and diagnosed, it is usually managed according to its BCLC stage.
      Patients with early-stage disease often benefit from potentially curative
      therapies, such as surgical resection and liver transplantation. Often, local
      ablation such as radiofrequency ablation or percutaneous alcohol injection can be
      used not only as an effective treatment, but also as a bridge therapy to maintain
      the status of patients on the liver transplant list. Intermediate-stage patients
      are typically treated with transarterial chemoembolization, but have a high rate
      of disease recurrence. The multikinase inhibitor sorafenib is the only treatment
      option approved for patients with advanced-stage HCC. Sorafenib has demonstrated
      a significant survival advantage in these patients. Numerous studies have
      evaluated other novel targeted therapies in this setting, but none have shown
      superiority to sorafenib. 

PMID- 24872794
TI  - A SPECIAL MEETING REVIEW EDITION: Clinical Research Highlights in IBD: Diagnosis
      and Anti-Tumor Necrosis Factor Monitoring: Digestive Disease Week 2013May 18-21,
      2013 * Orlando, FloridaSpecial Reporting on:* Serological and Inflammatory IBD
      Marker Prevalence As Function of Age in a Large Cohort of Patients Presenting IBD
      Like Gastrointestinal Symptoms* Prevalence of Antibodies to Adalimumab (ATA) and
      Correlation Between ATA and Low Serum Drug Concentration on CRP and Clinical
      Symptoms in a Prospective Sample of IBD Patients* Serum Adalimumab Levels and
      Antibodies Correlate with Endoscopic Intestinal Inflammation and Inflammatory
      Markers in Patients with Inflammatory Bowel Disease* Comparison of Early
      Measurement of Infliximab and Antibodies-to-Infliximab Serum Levels with Standard
      Trough Analysis* Trough Levels and Antidrug Antibodies Predict Safety and Success
      of Restarting Infliximab After a Long Drug Holiday* A Multi-Center Observational
      Study in Community Gastroenterology Practices Evaluating the Clinical Usage of
      Testing for Serum Levels of Infliximab and Antibodies to Infliximab* Preoperative
      Serum Biologic Levels Do Not Impact Postoperative Outcomes in Ulcerative Colitis*
      Higher Preoperative Serum Biologic Levels Are Associated with Postoperative
      Complications in Crohn's Disease PatientsWith Expert Commentary by: William J.
      Sandborn, MDProfessor and Chief, Division of GastroenterologyDirector, UCSD IBD
      CenterUC San Diego Health SystemLa Jolla, California.

PMID- 24872795
TI  - Some aspects of formation and tribological properties of silver nanodumbbells.
AB  - In this paper, metal nanodumbbells (NDs) formed by laser-induced melting of Ag
      nanowires (NWs) on an oxidized silicon substrate and their tribological
      properties are investigated. The mechanism of ND formation is proposed and
      illustrated with finite element method simulations. Tribological measurements
      consist in controllable real-time manipulation of NDs inside a scanning electron
      microscope (SEM) with simultaneous force registration. The geometry of NDs
      enables to distinguish between different types of motion, i.e. rolling, sliding
      and rotation. Real contact areas are calculated from the traces left after the
      displacement of NDs and compared to the contact areas predicted by the contact
      mechanics and frozen droplet models. PACS: 81.07.-b; 62.25.-g; 62.23.Hj.

PMID- 24872797
TI  - Morphological effect of oscillating magnetic nanoparticles in killing tumor
      cells.
AB  - Forced oscillation of spherical and rod-shaped iron oxide magnetic nanoparticles
      (MNPs) via low-power and low-frequency alternating magnetic field (AMF) was
      firstly used to kill cancer cells in vitro. After being loaded by human cervical
      cancer cells line (HeLa) and then exposed to a 35-kHz AMF, MNPs mechanically
      damaged cell membranes and cytoplasm, decreasing the cell viability. It was found
      that the concentration and morphology of the MNPs significantly influenced the
      cell-killing efficiency of oscillating MNPs. In this preliminary study, when HeLa
      cells were pre-incubated with 100 MUg/mL rod-shaped MNPs (rMNP, length of 200 +/-
      50 nm and diameter of 50 to 120 nm) for 20 h, MTT assay proved that the cell
      viability decreased by 30.9% after being exposed to AMF for 2 h, while the cell
      viability decreased by 11.7% if spherical MNPs (sMNP, diameter of 200 +/- 50 nm)
      were used for investigation. Furthermore, the morphological effect of MNPs on
      cell viability was confirmed by trypan blue assay: 39.5% rMNP-loaded cells and
      15.1% sMNP-loaded cells were stained after being exposed to AMF for 2 h. It was
      also interesting to find that killing tumor cells at either higher (500 MUg/mL)
      or lower (20 MUg/mL) concentration of MNPs was less efficient than that achieved
      at 100 MUg/mL concentration. In conclusion, the relatively asymmetric
      morphological rod-shaped MNPs can kill cancer cells more effectively than
      spherical MNPs when being exposed to AMF by virtue of their mechanical
      oscillations. 

PMID- 24872798
TI  - Alpha-helical regions of the protein molecule as organic nanotubes.
AB  - An alpha-helical region of protein molecule was considered in a model of
      nanotube. The molecule is in conditions of quantum excitations. Such model
      corresponds to a one-dimensional molecular nanocrystal with three molecules in an
      elementary cell at the presence of excitation. For the analysis of different
      types of conformational response of the alpha-helical area of the protein
      molecule on excitation, the nonlinear response of this area to the intramolecular
      quantum excitation caused by hydrolysis of adenosine triphosphate (ATP) is taken
      into account. It has been established that in the simplest case, three types of
      excitation are realized. As estimates show, each of them 'serves' different kinds
      of protein. The symmetrical type of excitation, most likely, is realized in the
      reduction of traversal-striped skeletal muscles. It has the highest excitation
      energy. This well protects from casual actions. Antisymmetric excitations have
      intermediate energy (between symmetrical and asymmetrical). They, most likely,
      are realized in membranous and nucleic proteins. It is shown that the
      conformational response of the alpha-helical region of the protein is (in
      angstroms) a quantity of order N c /5, where N c is the number of spiral turns.
      For the number of turns typical in this case: N c  ~ 10, displacement compounds
      are a quantity of order 2 A. It qualitatively corresponds to observable values.
      Asymmetrical excitations have the lowest energy. Therefore, most likely, they are
      realized in enzymatic proteins. It was shown that at this type of excitation, the
      bending of the alpha-helix is formally directed to the opposite side with respect
      to the antisymmetric excitations. Also, it has a greater value than the
      antisymmetric case for N c  <= 14 and smaller for N c  > 14. PACS: 92C05. MCS:
      36.20.Ey.

PMID- 24872796
TI  - Oxygen-containing functional group-facilitated CO2 capture by carbide-derived
      carbons.
AB  - A series of carbide-derived carbons (CDCs) with different surface oxygen contents
      were prepared from TiC powder by chlorination and followed by HNO3 oxidation. The
      CDCs were characterized systematically by a variety of means such as Fourier
      transform infrared spectroscopy, X-ray photoelectron spectroscopy, ultimate
      analysis, energy dispersive spectroscopy, N2 adsorption, and transmission
      electron microscopy. CO2 adsorption measurements showed that the oxidation
      process led to an increase in CO2 adsorption capacity of the porous carbons.
      Structural characterizations indicated that the adsorbability of the CDCs is not
      directly associated with its microporosity and specific surface area. As
      evidenced by elemental analysis, X-ray photoelectron spectroscopy, and energy
      dispersive spectroscopy, the adsorbability of the CDCs has a linear correlation
      with their surface oxygen content. The adsorption mechanism was studied using
      quantum chemical calculation. It is found that the introduction of O atoms into
      the carbon surface facilitates the hydrogen bonding interactions between the
      carbon surface and CO2 molecules. This new finding demonstrated that not only the
      basic N-containing groups but also the acidic O-containing groups can enhance the
      CO2 adsorbability of porous carbon, thus providing a new approach to design
      porous materials with superior CO2 adsorption capacity. 

PMID- 24872799
TI  - Improved dye-sensitized solar cell with a ZnO nanotree photoanode by hydrothermal
      method.
AB  - This study investigated the influence of ZnO nanostructures on dye adsorption to
      increase the photovoltaic conversion efficiency of solar cells. ZnO
      nanostructures were grown in both tree-like and nanorod (NR) arrays on an AZO/FTO
      film structure by using a hydrothermal method. The results were observed in
      detail using X-ray diffraction, field-emission scanning electron microscopy (FE
      SEM), UV-visible spectrophotometry, electrochemical impedance spectroscopy, and
      solar simulation. The selective growth of tree-like ZnO was found to exhibit
      higher dye adsorption loading and conversion efficiency than ZnO NRs. The
      multiple 'branches' of 'tree-like nanostructures' increases the surface area for
      higher light harvesting and dye loading while reducing charge recombination.
      These improvements result in a 15% enhancement in power conversion. The objective
      of this study is to facilitate the development of a ZnO-based dye-sensitized
      solar cell. 

PMID- 24872801
TI  - Structure, tribotechnical, and thermophysical characteristics of the
      fluoroplastic carbonnanotubes material.
AB  - In this work, we studied a nanocomposite material made from fluoroplastic which
      contains 20 wt.% multi-walled nanotubes. In order to complete the present work,
      we have used different thermodynamic and mechanical techniques. The introduction
      of nanotubes in the F4 polymer matrix has completely changed the tribological and
      thermodynamic properties of the studied nanocomposite material. The compression
      strength becomes 20% higher than that of the F4 polymer matrix. Meanwhile the
      wear resistance achieves an order of magnitude 100 times greaterthan that of F4.
      Moreover, a friction coefficient is about 25% to 30% lower than that of a similar
      material and especially that of F4 material. Differential scanning calorimetric
      study showed that the glassy phase transition appears at about 330 degrees C,
      which confirms that the degradation of the studied nanocomposite occurs at
      relatively higher temperature. This result confirms the one concerning the change
      in tribological properties. Dilatometric study revealed that the thermal
      expansion coefficient has been increased. The observed relative elongation
      measurement change depends on the direction along which the measurement has been
      done and confirms, in turn, the anisotropic character of the studied material.
      These results suggest that the metallic materials could be replaced by
      nanocomposite compounds which present good physical properties. 

PMID- 24872800
TI  - Synthesis and characterization of single-crystalline zinc tin oxide nanowires.
AB  - Crystalline zinc tin oxide (ZTO; zinc oxide with heavy tin doping of 33 at.%)
      nanowires were first synthesized using the electrodeposition and heat treatment
      method based on an anodic aluminum oxide (AAO) membrane, which has an average
      diameter of about 60 nm. According to the field emission scanning electron
      microscopy (FE-SEM) results, the synthesized ZTO nanowires are highly ordered and
      have high wire packing densities. The length of ZTO nanowires is about 4 MUm, and
      the aspect ratio is around 67. ZTO nanowires with a Zn/(Zn + Sn) atomic ratio of
      0.67 (approximately 2/3) were observed from an energy dispersive spectrometer
      (EDS). X-ray diffraction (XRD) and corresponding selected area electron
      diffraction (SAED) patterns demonstrated that the ZTO nanowire is hexagonal
      single-crystalline. The study of ultraviolet/visible/near-infrared (UV/Vis/NIR)
      absorption showed that the ZTO nanowire is a wide-band semiconductor with a band
      gap energy of 3.7 eV. 

PMID- 24872802
TI  - Preparation and ageing-resistant properties of polyester composites modified with
      functional nanoscale additives.
AB  - This study investigated ageing-resistant properties of carboxyl-terminated
      polyester (polyethylene glycol terephthalate) composites modified with nanoscale
      titanium dioxide particles (nano-TiO2). The nano-TiO2 was pretreated by a dry
      coating method, with aluminate coupling agent as a functional grafting additive.
      The agglomeration resistance was evaluated, which exhibited significant
      improvement for the modified nanoparticles. Then, the effects of the modified
      nano-TiO2 on the crosslinking and ageing-resistant properties of the composites
      were studied. With a real-time Fourier transform infrared (FT-IR) measurement,
      the nano-TiO2 displayed promoting effect on the crosslinking of polyester resin
      with triglycidyl isocyanurate (TGIC) as crosslinking agent. Moreover, the gloss
      retention, colour aberration and the surface morphologies of the composites
      during accelerated UV ageing (1500 hours) were investigated. The results
      demonstrated much less degree of ageing degradation for the nanocomposites,
      indicating an important role of the nano-TiO2 in improving the ageing-resistant
      properties of synthetic polymer composites. 

PMID- 24872803
TI  - Synthesis of silver nanoparticles and antibacterial property of silk fabrics
      treated by silver nanoparticles.
AB  - A silver nanoparticle solution was prepared in one step by mixing AgNO3 and a
      multi-amino compound (RSD-NH2) solution under ambient condition. RSD-NH2 was in
      house synthesized by methacrylate and polyethylene polyamine in methanol, which
      has abundant amino and imino groups. However, the characterization of silver
      nanoparticles indicated that these nanoparticles are easy to agglomerate in
      solution. Therefore, an in situ synthesis method of silver nanoparticles on the
      silk fabrics was developed. The examined results confirmed that the in situ
      synthesized silver nanoparticles were evenly distributed on the surface of
      fibers. The inhibition zone test and the antibacterial rate demonstrated that the
      finished fabrics have an excellent antibacterial property against Staphylococcus
      aureus and Escherichia coli. Moreover, the nanosilver-treated silk fabrics were
      laundered 0, 5, 10, 20, and 50 times and still retained the exceptional
      antibacterial property. When the treated fabrics were washed 50 times, the
      antibacterial rate is more than 97.43% for S. aureus and 99.86% for E. coli. The
      excellent laundering durability may be attributed to the tight binding between
      silver nanoparticles and silk fibers through the in situ synthesis. This method
      provides an economic method to enhance the antibacterial capability of silk
      fabrics with good resistance to washings. 

PMID- 24872804
TI  - Relaxation processes in hybrid organic-inorganic polymer nanosystems polymerized
      in situ.
AB  - The relaxation processes of hybrid organic-inorganic polymer nanosystems (OIS)
      synthesized by joint polymerization of organic and inorganic components were
      studied using methods of differential scanning calorimetry (DSC), dynamic
      mechanical thermal analysis (DMTA), and broadband dielectric relaxation
      spectroscopy (DRS). The organic component was a mixture of two products: high
      molecular-weight macrodiisocyanate (MDI) with low reactivity and low-molecular
      weight isocyanate-containing modifier poly(isocyanate) (PIC) with high
      reactivity. Sodium silicate (SS) was used as inorganic component. The structures
      of the OIS obtained were in the form of hybrids with covalently connected
      building blocks and interpenetrating networks: weakly cross-linked network MDI/SS
      and highly cross-linked network PIC/SS. Depending on the MDI/PIC ratio, one of
      the networks was prevailing and created a continuous structure with domains of
      second network. PACS: 61.25.hk; 82.35.Lr; 64.70.pj.

PMID- 24872805
TI  - Microstructure and optical properties of nanocrystalline Cu2O thin films prepared
      by electrodeposition.
AB  - Cuprous oxide (Cu2O) thin films were prepared by using electrodeposition
      technique at different applied potentials (-0.1, -0.3, -0.5, -0.7, and -0.9 V)
      and were annealed in vacuum at a temperature of 100 degrees C for 1 h.
      Microstructure and optical properties of these films have been investigated by X
      ray diffractometer (XRD), field-emission scanning electron microscope (SEM), UV
      visible (vis) spectrophotometer, and fluorescence spectrophotometer. The
      morphology of these films varies obviously at different applied potentials.
      Analyses from these characterizations have confirmed that these films are
      composed of regular, well-faceted, polyhedral crystallites. UV-vis absorption
      spectra measurements have shown apparent shift in optical band gap from 1.69 to
      2.03 eV as the applied potential becomes more cathodic. The emission of FL
      spectra at 603 nm may be assigned as the near band-edge emission. 

PMID- 24872806
TI  - Templated growth of PFO-DBT nanorod bundles by spin coating: effect of spin
      coating rate on the morphological, structural, and optical properties.
AB  - In this study, the spin coating of template-assisted method is used to synthesize
      poly[2,7-(9,9-dioctylfluorene)-alt-4,7-bis(thiophen-2-yl)benzo-2,1,3-thiadiazole]
      (PFO-DBT) nanorod bundles. The morphological, structural, and optical properties
      of PFO-DBT nanorod bundles are enhanced by varying the spin coating rate (100,
      500, and 1,000 rpm) of the common spin coater. The denser morphological
      distributions of PFO-DBT nanorod bundles are favorably yielded at the low spin
      coating rate of 100 rpm, while at high spin coating rate, it is shown otherwise.
      The auspicious morphologies of highly dense PFO-DBT nanorod bundles are supported
      by the augmented absorption and photoluminescence. 

PMID- 24872807
TI  - Reduction of friction and wear by grooves applied on the nanoscale polished
      surface in boundary lubrication conditions.
AB  - The evolution of a friction surface geometry with initially directed microscale
      grooves on a nanoscale polished surface in ring-on-block sliding contact is
      studied experimentally. Reduced wear and friction is observed when the
      orientation of grooves coincides with the direction of sliding. A new compressive
      vacuum hypothesis of friction force nature under a condition of boundary
      lubrication is proposed, which successfully explains the observed phenomena.
      Grooves supply lubricant into the contact zone and facilitate its
      devacuumization, which lead to substantial reduction of surface wear. The
      obtained results enable developing optimized roughness profiles of friction
      surfaces to create high-performance durable friction units. 

PMID- 24872808
TI  - Synthesis and structure of undoped and indium-doped thermoelectric lead telluride
      nanoparticles.
AB  - Undoped and indium (In)-doped lead telluride (PbTe) nanostructures were
      synthesized via solvothermal/hydrothermal route. The crystalline structure of the
      as-prepared undoped and In-doped PbTe samples was examined by X-ray diffraction
      (XRD) which indicated the formation of face-centered single-phase cubic crystal.
      A first principle calculation on indium doping shows that the indium atoms are
      more likely to replace lead (Pb) rather than to take the interstitial sites.
      Laser-induced breakdown spectroscopy (LIBS) analysis confirms that indium is
      incorporated into the PbTe matrix of the indium-doped PbTe samples. The effects
      of surfactant and synthesis temperature on the structure and morphology of the
      undoped PbTe were also investigated; it was found that PbTe nanostructures
      synthesized with the addition of surfactants exhibited uniform shapes and their
      size increased with the synthesis temperature. 

PMID- 24872809
TI  - Mass spectrometry-based N-glycoproteomics for cancer biomarker discovery.
AB  - Glycosylation is estimated to be found in over 50% of human proteins. Aberrant
      protein glycosylation and alteration of glycans are closely related to many
      diseases. More than half of the cancer biomarkers are glycosylated-proteins, and
      specific glycoforms of glycosylated-proteins may serve as biomarkers for either
      the early detection of disease or the evaluation of therapeutic efficacy for
      treatment of diseases. Glycoproteomics, therefore, becomes an emerging field that
      can make unique contributions to the discovery of biomarkers of cancers. The
      recent advances in mass spectrometry (MS)-based glycoproteomics, which can
      analyze thousands of glycosylated-proteins in a single experiment, have shown
      great promise for this purpose. Herein, we described the MS-based strategies that
      are available for glycoproteomics, and discussed the sensitivity and high
      throughput in both qualitative and quantitative manners. The discovery of
      glycosylated-proteins as biomarkers in some representative diseases by employing
      glycoproteomics was also summarized. 

PMID- 24872810
TI  - Risk of psychiatric and neurological diseases in patients with workplace mobbing
      experience in Germany: a retrospective database analysis.
AB  - INTRODUCTION: The number of mobbing experiences recorded has increased during
      recent years and it has now been established as global phenomenon among the
      working population. The goal of our study was to analyze the incidence of certain
      neurologic and psychiatric diseases as a consequence of mobbing as compared with
      a control group and to examine the possible influence of previous diseases that
      occurred within one year before the first mobbing documentation on the incidence
      of mobbing. MATERIAL & METHODS: We used a large database (IMS(r) Disease
      Analyzer, Germany) to collect data from general practitioners in Germany from
      01/2003 until 12/2012. Based on age, gender, and health insurance, patients with
      experience of mobbing were matched with a control group of patients who had not
      reported workplace mobbing and who were being treated by the same physicians. At
      first, diseases that occurred within one year before the bullying experience took
      place ("index date") were noted and compared to a control group of similar
      composition in terms of gender, age, and health insurance. Subsequently, the
      prevalence of depression, anxiety, somatoform disorders, and sleep disorders
      following experiences of mobbing were determined. After adjustment to take into
      account the odds of bullying, the ratios of these diseases were assessed using a
      logistic regression model. RESULTS: The study population consisted of n=2,625
      patients and n=2,625 controls, of which 33% were men. The number of cases of
      bullying documented rose continuously from 2003 to 2011 and remained high in
      2012. Those who would later become victims of mobbing demonstrated a considerably
      higher prevalence of diseases in general - these diseases were not confined to
      the neurologic-psychiatric spectrum. Following experiences of bullying,
      depression, anxiety, somatoform disorders, and sleep disorders were significantly
      more prevalent than in the control group (for all, p<0.05). Similarly, odds
      ratios (OR) representing the risk of suffering from diseases were higher in
      affected patients, with the highest value (4.28) for depression and the lowest
      value for sleep disorders (OR=2.4). CONCLUSION: Those who will later become the
      victims of bullying are more prone to suffer from diseases in general, even
      before this experience of mobbing has occurred, which underlines the importance
      of supporting (chronically) ill patients to protect them against bullying.
      Sequelae of mobbing include, in particular, diseases from the neurologic
      psychiatric spectrum.

PMID- 24872811
TI  - The union of narrative and executive function: different but complementary.
AB  - Oral narrative production develops dramatically from 3 to 5 years of age, and is
      a key factor in a child's ability to communicate about the world. Concomitant
      with this are developments in executive function (EF). For example, executive
      attention and behavioral inhibition show marked development beginning around 4
      years of age. Both EF and oral narrative abilities have important implications
      for academic success, but the relationship between them is not well understood.
      The present paper utilizes a cross-lagged design to assess convergent and
      predictive relations between EF and narrative ability. As a collateral measure,
      we collected a Language Sample during 10 min of free play. Language Sample did
      not share significant variance with Narrative Production, thus general language
      growth from Wave 1 to Wave 2 cannot account for the predictive relations between
      EF and Narrative. Our findings suggest that although EF and Narrative ability
      appear independent at each Wave, they nevertheless support each other over
      developmental time. Specifically, the ability to maintain focus at 4 years
      supports subsequent narrative ability and narrative ability at 4 years supports
      subsequent facility and speed in learning and implementing new rules. 

PMID- 24872812
TI  - Association between Lower Normal Free Thyroxine Concentrations and Obesity
      Phenotype in Healthy Euthyroid Subjects.
AB  - We investigated whether thyroid function could identify obesity phenotype in
      euthyroid subjects. A cross-sectional analysis was performed among nondiabetic,
      euthyroid subjects. We stratified subjects into four groups by BMI and insulin
      resistance (IR). Of 6241 subjects, 33.8% were overweight or obese (OW/OB) and
      66.2% were normal weight (NW). Free thyroxine (FT4) levels were negatively
      associated with body mass index, waist circumference, triglyceride, c-reactive
      protein, and HOMA-IR and positively with high-density lipoprotein cholesterol in
      both genders. In multivariate regression analysis, FT4 level, a continuous
      measurement, was negatively correlated with HOMA-IR (beta = -0.155, P < 0.001 in
      men; beta = -0.175, P < 0.001 in women). After adjustment for age, sex,
      metabolic, and life style factors, subjects in the lowest FT4 quartile had an
      odds ratio (OR) for IR of 1.99 (95% confidence interval 1.61-2.46), as compared
      to those in the highest quartile. The association between low FT4 and IR remained
      significant in both NW and OW/OB subgroups. In conclusion, low normal FT4 levels
      were independently related to IR in NW and OW/OB euthyroid subjects. Further
      studies are needed to investigate the mechanisms by which low FT4 levels are
      linked to high IR in euthyroid ranges. 

PMID- 24872815
TI  - A case-control study of the role of human papillomavirus in oesophageal squamous
      cell carcinoma in australia.
AB  - Objective. We investigate the prevalence of human papillomavirus (HPV) in
      oesophageal squamous cell carcinoma (OSCC) tissues compared to oesophageal tissue
      from healthy controls, in an Australian cohort. Methods. We conducted a hospital
      based case-control study of 99 patients with OSCC and 100 healthy controls to
      examine the presence of HPV DNA. Paraffin tissues were tested using the PapType
      high-risk HPV detection and genotyping kit and with INNO-LiPA HPV Genotyping
      Extra. The biopsy samples were tested for HPV using a PCR-ELISA method based on
      the L1 consensus primer set PGMY09-PGMY11. Results. HPV DNA of the oncogenic
      genotype 16 was detected in 1/99 case specimens, a rate of 1010 per 100,000 (95%
      CI: 30-5500). All control specimens were negative for HPV. Significantly higher
      rates of smoking, other aerodigestive cancers, and mortality were seen among
      cases than controls. A pooled analysis of this study and the only other
      Australian case-control study found that 9/321 cases and 0/155 controls were
      positive for HPV. The pooled odds ratio for HPV being a risk factor for OSCC was
      9.35 (95% CI: 0.47-190.33). Conclusion. Our results suggest that in this
      multifactorial cancer HPV may be an additional risk factor; although a larger,
      better powered study is needed. 

PMID- 24872817
TI  - Development of phantom limb pain after femoral nerve block.
AB  - Historically, phantom limb pain (PLP) develops in 50-80% of amputees and may
      arise within days following an amputation for reasons presently not well
      understood. Our case involves a 29-year-old male with previous surgical
      amputation who develops PLP after the performance of a femoral nerve block.
      Although there have been documented cases of reactivation of PLP in amputees
      after neuraxial technique, there have been no reported events associated with
      femoral nerve blockade. We base our discussion on the theory that symptoms of
      phantom limb pain are of neuropathic origin and attempt to elaborate the link
      between regional anesthesia and PLP. Further investigation and understanding of
      PLP itself will hopefully uncover a relationship between peripheral nerve blocks
      targeting an affected limb and the subsequent development of this phenomenon,
      allowing physicians to take appropriate steps in prevention and treatment. 

PMID- 24872816
TI  - The kikuchi-fujimoto disease in Nigeria: a case report and literature review.
AB  - The Kikuchi-Fujimoto is a rare, self-limiting disease, which is characterized by
      regional lymphadenopathy. It occurs worldwide with a higher prevalence among
      Asians and women below the age of forty years. We present 41-year-old Nigerian
      woman who was investigated extensively for unilateral left cervical
      lymphadenopathy. She was eventually diagnosed as having the Kikuchi-Fujimoto
      disease and was managed conservatively thereafter. We describe a case report and
      review of literature for better awareness of the disease amongst medical
      practitioners and pathologists in Africa. 

PMID- 24872814
TI  - Coordinated Actions of FXR and LXR in Metabolism: From Pathogenesis to
      Pharmacological Targets for Type 2 Diabetes.
AB  - Type 2 diabetes (T2D) is the most prevalent metabolic disease, and many people
      are suffering from its complications driven by hyperglycaemia and dyslipidaemia.
      Nuclear receptors (NRs) are ligand-inducible transcription factors that mediate
      changes to metabolic pathways within the body. As metabolic regulators, the
      farnesoid X receptor (FXR) and the liver X receptor (LXR) play key roles in the
      pathogenesis of T2D, which remains to be clarified in detail. Here we review the
      recent progress concerning the physiological and pathophysiological roles of FXRs
      and LXRs in the regulation of bile acid, lipid and glucose metabolism and the
      implications in T2D, taking into account that these two nuclear receptors are
      potential pharmaceutical targets for the treatment of T2D and its complications. 

PMID- 24872818
TI  - Mucormycosis in patients with inflammatory bowel disease: case series and review
      of the literature.
AB  - Mucormycosis is a rare and often fatal invasive fungal infection mostly seen in
      immune-compromised individuals. A high index of clinical suspicion is necessary,
      so that effective preemptive therapy can be started, as timely intervention is
      crucial. In this series we present three cases of invasive mucormycosis in
      patients with underlying inflammatory bowel disease that had received therapy
      with immunomodulators prior to the infection. All three had varied clinical
      manifestations. We also review the literature of invasive mucormycosis in
      patients with inflammatory bowel disease. 

PMID- 24872819
TI  - Purulent pericarditis after liver abscess: a case report.
AB  - We present the case of a 49-year-old woman, with previous clinical antecedents of
      recent hepatic metastasis, who was admitted to the ICU due to respiratory failure
      and hemodynamic instability. She was found to have purulent pericarditis
      complicated by pericardial tamponade and pleural effusion, as well as surgical
      site infection, which was the origin of the disease. Cultures of the surgical
      wound and the pericardial effusion were positive for Enterococcus faecalis and
      Escherichia coli. A pericardial tap was performed and the intra-abdominal abscess
      was surgically drained. Pleural effusion was also evacuated. She received
      antibiotic treatment and recovered successfully. The only after-effect was a well
      tolerated effusive-constrictive pericarditis. 

PMID- 24872822
TI  - Funding for mental health research: looking ahead.

PMID- 24872820
TI  - Probiotics in the treatment of chronic rhinoconjunctivitis and chronic
      rhinosinusitis.
AB  - Chronic rhinitis and rhinosinusitis (CRS) are relevant health conditions
      affecting significant percentages of the western population. They are frequently
      coexisting and aggravating diseases. Both are chronic, noninfectious, and
      inflammatory conditions sharing to a certain extent important pathophysiologic
      similarities. Beneficial effects of probiotics are long known to mankind.
      Research is beginning to unravel the true nature of the human microbiome and its
      interaction with the immune system. The growing prevalence of atopic diseases in
      the developed world led to the proposition of the "hygiene hypothesis." Dysbiosis
      is linked to atopic diseases; probiotic supplementation is able to alter the
      microbiome and certain probiotic strains have immunomodulatory effects in favour
      of a suppression of Th-2 and stimulation of a Th1 profile. This review focuses on
      randomized, double-blind, placebo-controlled trials investigating clinical
      parameters in the treatment of chronic rhinitis and CRS. An emerging number of
      publications demonstrate beneficial effects using probiotics in clinical double
      blind placebo-controlled (dbpc) trials in allergic rhinitis (AR). Using
      probiotics as complementary treatment options in AR seems to be a promising
      concept although the evidence is of a preliminary nature to date and more
      convincing trials are needed. There are no current data to support the use of
      probiotics in non-AR or CRS. 

PMID- 24872823
TI  - Trauma informed care.

PMID- 24872821
TI  - Implications to payers of switch from hospital-based intravenous immunoglobulin
      to home-based subcutaneous immunoglobulin therapy in patients with primary and
      secondary immunodeficiencies in Canada.
AB  - BACKGROUND: Switching primary/secondary immunodeficiency (PID/SID) patients from
      intravenous immunoglobulin (IVIg) to home-based subcutaneous immunoglobulin
      (SCIg) therapy reduces nurse time. A nurse shortage in Canada provides an
      important context to estimate the net economic benefit, the number of patients
      needed to switch to SCIg to recoup one full-time equivalent (FTE), and potential
      population-wide savings of reduced nurse time to a payer. METHODS: The net
      economic benefit was estimated by multiplying the hourly compensation for nurses
      in Canada by the hours required for each administration route. The number needed
      to switch to SCIg to gain one nurse FTE was estimated by dividing the work hours
      in a year by the average annual savings in nursing time in a PID population in
      Canada. The prevalence of treated PID/SID in Canada was calculated using
      provincial IgG audit data to extrapolate the potential population-wide savings of
      switching patients to SCIg therapy. FINDINGS: The net economic gain from
      switching one patient to home-based SCIg care would be C$2,603 (Canadian Dollars)
      in year 1 and C$2,948 each year thereafter. Switching 37 IVIg patients to SCIg
      would gain one nurse FTE. Switching 50% of the estimated 5,486 PID and SID
      patients in Canada receiving IVIg therapy to SCIg has the potential to save 223.3
      nurse FTEs (C$23.2 million in labor costs). CONCLUSIONS: A shift from IVIg to
      less labor-intensive SCIg has the potential to help alleviate nurse shortages and
      reduce overall health care costs in Canada. Health care professionals might
      consider advocating for home-based SCIg therapy for PID/SID patients when
      clinically appropriate.

PMID- 24872824
TI  - Using technology to deliver mental health services to children and youth: a
      scoping review.
AB  - OBJECTIVE: To conduct a scoping review on the use of technology to deliver mental
      health services to children and youth in order to identify the breadth of peer
      reviewed literature, summarize findings and identify gaps. METHOD: A literature
      database search identified 126 original studies meeting criteria for review.
      Descriptive numerical summary and thematic analyses were conducted. Two reviewers
      independently extracted data. RESULTS: Studies were characterized by diverse
      technologies including videoconferencing, telephone and mobile phone applications
      and Internet-based applications such as email, web sites and CD-ROMs. CONCLUSION:
      The use of technologies plays a major role in the delivery of mental health
      services and supports to children and youth in providing prevention, assessment,
      diagnosis, counseling and treatment programs. Strategies are growing
      exponentially on a global basis, thus it is critical to study the impact of these
      technologies on child and youth mental health service delivery. An in-depth
      review and synthesis of the quality of findings of studies on effectiveness of
      the use of technologies in service delivery are also warranted. A full systematic
      review would provide that opportunity.

PMID- 24872825
TI  - The Psychosocial Characteristics Associated with NSSI and Suicide Attempt of
      Youth Admitted to an In-patient Psychiatric Unit.
AB  - INTRODUCTION: The purpose of this study was to explore the prevalence of self
      harm and the psychosocial factors associated with self-harming behaviours in
      youth admitted to an in-patient psychiatric unit. METHODS: Cross-sectional
      surveys of standardized measures were administered to youth and a separate survey
      to their caregivers while the youth were in hospital. RESULTS: The mean age of
      the 123 youth who participated was 15.74 (SD 1.51) years, and 90 of 121 (74.38%)
      reported being female. Of the 115 who completed this question, 101 (87.83%)
      indicated that they thought of injuring themselves and 89 (77.39%) did engage in
      NSSI within the past month, and 78 of 116 (67%) reported that they had made an
      attempt to take their life. Youth who reported that they had attempted suicide
      (lifetime) reported significantly less difficulty with emotion regulation than
      youth who engaged in NSSI only, or both NSSI and suicide attempts. CONCLUSIONS:
      These youth reported a very high prevalence of self-harm, and in general
      substantial difficulty with regulating their emotions, and difficulty with their
      interpersonal relationships. The psychosocial distinctions evident between groups
      may have practical utility.

PMID- 24872826
TI  - Characteristics of children and youth who visit the emergency department for a
      behavioural disorder.
AB  - OBJECTIVE: Relatively little is known about children who present to emergency
      departments (EDs) to stabilize acute emergencies related to behavioural
      disorders. This study describes patient and treatment characteristics of such
      children/youth. METHODS: We conducted a retrospective medical record review of
      consecutive ED presentations made by children/youth (10 to 17 years) between
      January 2009 and December 2011 for visits with a main discharge diagnosis of
      hyperkinetic disorder, mixed disorder of conduct and emotions, or conduct
      disorder. Socio-demographic and ED visit data were analyzed descriptively.
      RESULTS: During the study period, 365 consecutive presentations made by 325
      children/youth. The most common presenting complaints were related to
      depression/self-harm (45.8%) and violent behaviours (28.8%). Many children/youth
      had a previously diagnosed psychiatric disorder (59.4%) and identified being
      under the care of a child psychiatrist (42.2%). The majority of ED visits were
      triaged as urgent or emergent (51.5% and 41.1%, respectively) and included mood
      and suicidality assessments (84.7% and 80.8%, respectively). Follow-up with
      various services was made for all visits. CONCLUSION: Children and youth
      presented to the ED for a behavioural disorder had urgent needs related to self
      harm, depression and violent behaviours. These findings draw attention to the
      important role of the ED in managing physical safety and well-being concerns for
      families and recommending follow-up in the post-crisis period.

PMID- 24872827
TI  - Factors Associated with Parental Satisfaction with a Pediatric Crisis Clinic
      (PCC).
AB  - INTRODUCTION: Little is known about parental satisfaction with pediatric crisis
      clinics (PCCs) that provide a single consultation to families in need of urgent
      psychiatric care. Parental satisfaction may improve long-term adherence to
      physician recommendations. OBJECTIVE: To explore parental satisfaction with a
      PCC. METHODS: Parental satisfaction was ascertained by a structured telephone
      interview following crisis consultation at the PCC of an academic, tertiary care
      centre. METHODS: Parents of 71% (n = 124) of 174 pediatric patients seen in the
      PCC from 2007-2008 participated in the post-consultation interview. RESULTS: The
      majority of parents stated they were either somewhat satisfied (49/122, 40.2%) or
      very satisfied (49/122, 40.2%) with the PCC. Parental satisfaction correlated
      with time between referral and consultation (p<0.05), the degree to which parents
      felt listened to by the consultant (p<0.01), the amount of psychoeducation
      parents felt they received (p<0.01), and appointment length (p<0.001).
      CONCLUSIONS: Parents were satisfied overall with an urgent care service model.
      Satisfaction was correlated with the time between referral and consultation,
      degree to which they felt their consultant had listened to them, and the amount
      of information they received at the consultation's conclusion.

PMID- 24872828
TI  - Childhood ADHD and addictive behaviours in adolescence: a canadian sample.
AB  - OBJECTIVE: To compare rates of early addictive behaviours in a clinic sample of
      youth with childhood attention-deficit/hyperactivity disorder (ADHD) with those
      in community populations. METHOD: We surveyed 142 adolescents (14.1 +/- 1.14
      years), diagnosed with ADHD before age 12, about early substance use and problem
      gambling using questions from two cross-sectional population studies: the
      Canadian National Longitudinal Survey of Children and Youth, Ontario subsample,
      (N=1,317; 10-15 years) and the Ontario Student Drug Use and Health Survey
      (N=9,288; 12-18 years). RESULTS: The ADHD sample reported using cigarettes, 17.8%
      (95% CI 12.1-25.5), alcohol, 27.1% (20.1-35.5), cannabis, 14.2% (8.9-21.7), at a
      similar or lower rate than the NLSCY (cigarettes, 28.3% (25.8-30.9), alcohol,
      28.6% (26.0-31.3), cannabis, 16.5% (14.0-19.4), and OSDUHS samples (cigarettes,
      21.9% (20.2-23.7), alcohol, 58.6% (56.0-61.2), cannabis, 26.0% (23.9-28.2). With
      regards to gambling, there is a non-significant trend for ADHD youth to report
      gambling more frequently than the provincial average, 7.9% (3.3-17.9) vs. 4.3%
      (2.9-6.3). CONCLUSIONS: Our findings support the emerging literature that youth
      diagnosed with ADHD in childhood may not be at greater risk for onset of
      substance use in early adolescence. The study identified two areas that warrant
      further investigation in this population; the possible increased risk for
      substance use among females and a trend toward early onset of gambling
      behaviours.

PMID- 24872830
TI  - Commentary: Developmental Trauma Disorder: A Missed Opportunity in DSM V.

PMID- 24872831
TI  - Mind over PMDD: A Glimpse into the Process of Pharmacotherapy-Psychotherapy
      Combination Treatment.
AB  - The practice of combining pharmacotherapy with psychotherapy is advocated for as
      treatment of choice for many psychiatric disorders. Despite an abundance of
      outcome studies addressing this subject, little has been written about the
      process of combined treatment, leaving clinicians with insufficient guidance as
      to the "how" of the medication-psychotherapy merger. This case report follows the
      treatment course of a fourteen-year-old young woman initially diagnosed with
      Premenstrual Dysphoric Disorder (PMDD) and provisional Generalized Anxiety
      Disorder (GAD). It demonstrates the benefits, drawbacks, possible pitfalls and
      successful outcome of combined therapy, an outcome which may not have been
      achieved had only one of the modalities been used. 

PMID- 24872829
TI  - Dimensions of Perfectionism in Children and Adolescents with Obsessive-compulsive
      Disorder.
AB  - OBJECTIVE: To measure the association of perfectionism with obsessive-compulsive
      and depressive symptoms in children and adolescents with obsessive-compulsive
      disorder (OCD). METHOD: Sample consisted of 94 youth (44 boys, 49 girls; mean age
      = 13.2 y, SD = 2.5 y) with a DSM-IV diagnosis of OCD. Perfectionism beliefs were
      measured with both the Adaptive/Maladaptive Perfectionism Scale (AMPS) and a 14
      item version of the Child and Adolescents Perfectionism Scale (CAPS-14). Using a
      hierarchical linear-regression model, we measured the association of
      perfectionist beliefs with severity of OCD and depressive symptoms. RESULTS: Both
      AMPS and CAPS-14 scores were associated with the severity of OCD symptoms in our
      sample. In addition, CAPS-14 scores were associated with the severity of
      depressive symptoms, even when OCD symptoms were taken into account. CONCLUSIONS:
      Our findings lend further support to the hypothesis that perfectionism in youth
      with OCD is associated with variation in the severity of OCD and depressive
      symptoms.

PMID- 24872832
TI  - Protective effect of ligustrazine on lumbar intervertebral disc degeneration of
      rats induced by prolonged upright posture.
AB  - Most chronic low back pain is the result of degeneration of the lumbar
      intervertebral disc. Ligustrazine, an alkaloid from Chuanxiong, reportedly is
      able to relieve pain, suppress inflammation, and treat osteoarthritis and it has
      the protective effect on cartilage and chondrocytes. Therefore, we asked whether
      ligustrazine could reduce intervertebral disc degeneration. To determine the
      effect of ligustrazine on disc degeneration, we applied a rat model. The
      intervertebral disc degeneration of the rats was induced by prolonged upright
      posture. We found that pretreatment with ligustrazine for 1 month recovered the
      structural distortion of the degenerative disc; inhibited the expression of type
      X collagen, matrix metalloproteinase (MMP)-13, and MMP3; upregulated type II
      collagen; and decreased IL-1 beta , cyclooxygenase (COX)-2, and inducible nitric
      oxide synthase (iNOS) expression. In conclusion, ligustrazine is a promising
      agent for treating lumbar intervertebral disc degeneration disease. 

PMID- 24872834
TI  - Myrcia bella Leaf Extract Presents Hypoglycemic Activity via PI3k/Akt Insulin
      Signaling Pathway.
AB  - Species of Myrcia are used by indigenous people and in traditional communities in
      Brazil for the treatment of Diabetes mellitus. We investigated the hypoglycemic
      effect of the extract of leaves of Myrcia bella in diabetic mice. The chemical
      fingerprinting of the 70% EtOH extract characterized as main constituents
      flavonoid aglycones, flavonoid-O-glycosides, and acylated flavonoid-O-glycosides
      derivatives of quercetin and myricetin. Mice were treated with saline or extract
      of M. bella (300 or 600 mg/Kg b.w.) for 14 days. Body weight and water and food
      intake were measured every day. Fasting blood glucose was measured weekly. At the
      end of the treatment, blood insulin, triglycerides, total cholesterol, and
      protein were measured. Glycogen content and expression of proteins of the insulin
      signaling pathway were measured in liver. The treatment with 600 mg/Kg reduced
      the fasting blood glucose in diabetic mice of the 7th day as water and food
      intake and increased hepatic glycogen. Total cholesterol and triglycerides were
      reduced in diabetic treated mice. The treatment increased the expression of IRS
      1, PI3-K, and AKT in the livers of diabetic treated mice. The results indicate
      that the extract of the leaves of Myrcia bella has hypoglycemic properties and
      possibly acts to regulate glucose uptake by the liver. 

PMID- 24872833
TI  - Historical perspective of traditional indigenous medical practices: the current
      renaissance and conservation of herbal resources.
AB  - In recent years, increasing numbers of people have been choosing herbal medicines
      or products to improve their health conditions, either alone or in combination
      with others. Herbs are staging a comeback and herbal "renaissance" occurs all
      over the world. According to the World Health Organization, 75% of the world's
      populations are using herbs for basic healthcare needs. Since the dawn of
      mankind, in fact, the use of herbs/plants has offered an effective medicine for
      the treatment of illnesses. Moreover, many conventional/pharmaceutical drugs are
      derived directly from both nature and traditional remedies distributed around the
      world. Up to now, the practice of herbal medicine entails the use of more than
      53,000 species, and a number of these are facing the threat of extinction due to
      overexploitation. This paper aims to provide a review of the history and status
      quo of Chinese, Indian, and Arabic herbal medicines in terms of their significant
      contribution to the health promotion in present-day over-populated and aging
      societies. Attention will be focused on the depletion of plant resources on earth
      in meeting the increasing demand for herbs. 

PMID- 24872835
TI  - The traditional kampo medicine tokishakuyakusan increases ocular blood flow in
      healthy subjects.
AB  - The aim of this study was to examine the effects of oral administration of kampo
      medical formulas on ocular blood flow (OBF). A crossover protocol was used to
      randomly administer five grams of yokukansan, tokishakuyakusan (TSS),
      keishibukuryogan, or hachimijiogan to 13 healthy blinded subjects (mean age: 37.3
      +/- 12.3 years). The mean blur rate, a quantitative OBF index obtained with laser
      speckle flowgraphy, was measured at the optic nerve head before and 30 minutes
      after administration. Blood pressure (BP) and intraocular pressure (IOP) were
      also recorded. No significant changes were observed in mean BP or IOP after the
      administration of any of the kampo medical formulas. There was a significant
      increase in OBF 30 minutes after administration of TSS (100% to 103.6 +/- 6.9%, P
      < 0.01). Next, TSS was administered to 19 healthy subjects (mean age: 32.0 +/-
      11.0 years) and OBF was measured before and 15, 30, 45, and 60 minutes after
      administration. Plain water was used as a control. OBF increased significantly
      after TSS administration compared to control (P < 0.01) and also increased from
      30 to 60 minutes after administration compared to baseline (P < 0.05). These
      results suggest that TSS can increase OBF without affecting BP or IOP in healthy
      subjects. 

PMID- 24872836
TI  - Hard times in the city - attractive nest sites but insufficient food supply lead
      to low reproduction rates in a bird of prey.
AB  - INTRODUCTION: Urbanization is a global phenomenon that is encroaching on natural
      habitats and decreasing biodiversity, although it is creating new habitats for
      some species. The Eurasian kestrel (Falco tinnunculus) is frequently associated
      with urbanized landscapes but it is unclear what lies behind the high densities
      of kestrels in the urban environment. RESULTS: Occupied nest sites in the city of
      Vienna, Austria were investigated along a gradient of urbanization (percentage of
      land covered by buildings or used by traffic). Field surveys determined the
      abundance of potential prey (birds and rodents) and the results were compared to
      the birds' diets. A number of breeding parameters were recorded over the course
      of three years. The majority of kestrels breed in semi-natural cavities in
      historic buildings. Nearest neighbour distances (NND) were smallest and
      reproductive success lowest in the city centre. Abundance of potential prey was
      not found to relate to the degree of urbanization but there was a significant
      shift in the birds' diets from a heavy reliance on rodents in the outskirts of
      the city to feeding more on small birds in the centre. The use of urban habitats
      was associated with higher nest failure, partly associated with predation and
      nest desertion, and with significantly lower hatching rates and smaller fledged
      broods. CONCLUSIONS: High breeding densities in urban habitats do not necessarily
      correlate with high habitat quality. The high density of kestrel nests in the
      city centre is probably due to the ready availability of breeding cavities.
      Highly urbanized areas in Vienna are associated with unexpected costs for the
      city dwelling-raptor, in terms both of prey availability and of reproductive
      success. The kestrel appears to be exploiting the urban environment but given the
      poor reproductive performance of urban kestrels it is likely that the species is
      falling into an ecological trap.

PMID- 24872838
TI  - Fluorescent labelling of the actin cytoskeleton in plants using a cameloid
      antibody.
AB  - BACKGROUND: Certain members of the Camelidae family produce a special type of
      antibody with only one heavy chain. The antigen binding domains are the smallest
      functional fragments of these heavy-chain only antibodies and as a consequence
      have been termed nanobodies. Discovery of these nanobodies has allowed the
      development of a number of therapeutic proteins and tools. In this study a class
      of nanobodies fused to fluorescent proteins (chromobodies), and therefore
      allowing antigen-binding and visualisation by fluorescence, have been used. Such
      chromobodies can be expressed in living cells and used as genetically encoded
      immunocytochemical markers. RESULTS: Here a modified version of the commercially
      available Actin-Chromobody(r) as a novel tool for visualising actin dynamics in
      tobacco leaf cells was tested. The actin-chromobody binds to actin in a specific
      manner. Treatment with latrunculin B, a drug which disrupts the actin
      cytoskeleton through inhibition of polymerisation results in loss of fluorescence
      after less than 30 min but this can be rapidly restored by washing out
      latrunculin B and thereby allowing the actin filaments to repolymerise. To test
      the effect of the actin-chromobody on actin dynamics and compare it to one of the
      conventional labelling probes, Lifeact, the effect of both probes on Golgi
      movement was studied as the motility of Golgi bodies is largely dependent on the
      actin cytoskeleton. With the actin-chromobody expressed in cells, Golgi body
      movement was slowed down but the manner of movement rather than speed was
      affected less than with Lifeact. CONCLUSIONS: The actin-chromobody technique
      presented in this study provides a novel option for in vivo labelling of the
      actin cytoskeleton in comparison to conventionally used probes that are based on
      actin binding proteins. The actin-chromobody is particularly beneficial to study
      actin dynamics in plant cells as it does label actin without impairing dynamic
      movement and polymerisation of the actin filaments.

PMID- 24872837
TI  - Systemic and tumor level iron regulation in men with colorectal cancer: a case
      control study.
AB  - BACKGROUND: Increased cellular iron exposure is associated with colorectal cancer
      (CRC) risk. Hepcidin, a liver peptide hormone, acts as the primary regulator of
      systemic iron status by blocking iron release from enterocytes into plasma.
      Concentrations are decreased during low iron status and increased during
      inflammation. The role of hepcidin and the factors influencing its regulation in
      CRC remains largely unknown. This study explored systemic and tumor level iron
      regulation in men with CRC. METHODS: The participants were 20 CRC cases and 20
      healthy control subjects. Colonic tissue (adenocarcinoma [cases] healthy mucosa
      [controls]) was subjected to quantitative PCR (hepcidin, iron transporters and IL
      6) and Perls' iron staining. Serum was analyzed using ELISA for hepcidin, iron
      status (sTfR) and inflammatory markers (CRP, IL-6, TNF-alpha). Anthropometrics,
      dietary iron intake and medical history were obtained. RESULTS: Cases and
      controls were similar in demographics, medication use and dietary iron intake.
      Systemically, cases compared to controls had lower iron status (sTfR: 21.6 vs
      11.8 nmol/L, p < 0.05) and higher marker of inflammation (CRP: 8.3 vs 3.4 MUg/mL,
      p < 0.05). Serum hepcidin was mildly decreased in cases compared to controls;
      however, it was within the normal range for both groups. Within colonic tissue,
      30% of cases (6/20) presented iron accumulation compared to 5% of controls (1/20)
      (chi(2) = 5.0; p < 0.05) and higher marker of inflammation (IL-6: 9.4-fold higher
      compared to controls, p < 0.05). Presence of adenocarcinoma iron accumulation was
      associated with higher serum hepcidin (iron accumulation group 80.8 vs iron
      absence group 22.0 ng/mL, p < 0.05). CONCLUSIONS: While CRC subjects had serum
      hepcidin concentrations in the normal range, it was higher given their degree of
      iron restriction. Inappropriately elevated serum hepcidin may reduce duodenal
      iron absorption and further increase colonic adenocarcinoma iron exposure. Future
      clinical studies need to assess the appropriateness of dietary iron intake or
      iron supplementation in patients with CRC.

PMID- 24872839
TI  - Genomic and functional analysis of the toxic effect of tachyplesin I on the
      embryonic development of zebrafish.
AB  - Tachyplesin I (TP I) is an antimicrobial peptide isolated from the hemocytes of
      the horseshoe crab. With the developments of DNA microarray technology, the
      genetic analysis of the toxic effect of TP I on embryo was originally considered
      in our recent study. Based on our microarray data of the embryonic samples of
      zebrafish treated with the different doses of TP I, we performed a series of
      statistical data analyses to explore the toxic effect of TP I at the genomic
      level. In this paper, we first employed the hexaMplot to illustrate the
      continuous variation of the gene expressions of the embryonic cells treated with
      the different doses of TP I. The probabilistic model-based Hough transform was
      used to classify these differentially coexpressed genes of TP I on the zebrafish
      embryos. As a result, three line rays supported with the corresponding 174 genes
      were detected in our analysis. Some biological processes of the featured genes,
      such as antigen processing, nuclear chromatin, and structural constituent of eye
      lens, were significantly filtered with the smaller P values. 

PMID- 24872840
TI  - A mathematical model of the immune and neuroendocrine systems mutual regulation
      under the technogenic chemical factors impact.
AB  - The concept of the triad regulatory metasystem, which includes the neuroendocrine
      and immune regulation systems, is currently generally accepted. Changes occurring
      in each of the regulatory systems in response to the impact of technogenic
      chemical factors are also well known. This paper presents mathematical models of
      the immune and neuroendocrine system functioning, using the interaction between
      these systems in response to bacterial invasion as an example, and changes in
      their performance under exposure to chemical factors, taking into account the
      stage of functional disorders in a producing organ, using the performance of the
      bone marrow as an example. 

PMID- 24872841
TI  - Blunt cerebrovascular injury in rugby and other contact sports: case report and
      review of the literature.
AB  - Contact sports have long been a part of human existence. The two earliest
      recorded organized contact games, both of which still exist, include Royal
      Shrovetide Football played since the 12(th) century in England and Caid played
      since 1308 AD in Ireland. Rugby is the premier contact sport played throughout
      the world with the very popular derivative American football being the premier
      contact sport of the North American continent. American football in the USA has
      on average 1,205,037 players at the high school and collegiate level per year
      while rugby in the USA boasts a playing enrollment of 457,983 at all levels.
      Recent media have highlighted injury in the context of competitive contact sports
      including their long-term sequelae such as chronic traumatic encephalopathy (CTE)
      that had previously been underappreciated. Blunt cerebrovascular injury (BCVI)
      has become a recognized injury pattern for trauma; however, a paucity of data
      regarding this injury can be found in the sports trauma literature. We present a
      case of an international level scrum-half playing Rugby Union at club level for a
      local non-professional team, in which a player sustained a fatal BCVI followed by
      a discussion of the literature surrounding sport related BCVI. 

PMID- 24872843
TI  - Mycoplasma contamination in the 1000 Genomes Project.
AB  - BACKGROUND: In silco Biology is increasingly important and is often based on
      public data. While the problem of contamination is well recognised in
      microbiology labs the corresponding problem of database corruption has received
      less attention. RESULTS: Mapping 50 billion next generation DNA sequences from
      The Thousand Genome Project against published genomes reveals many that match one
      or more Mycoplasma but are not included in the reference human genome GRCh37.p5.
      Many of these are of low quality but NCBI BLAST searches confirm some high
      quality, high entropy sequences match Mycoplasma but no human sequences.
      CONCLUSIONS: It appears at least 7% of 1000G samples are contaminated.

PMID- 24872842
TI  - Cordyceps cicadae induces G2/M cell cycle arrest in MHCC97H human hepatocellular
      carcinoma cells: a proteomic study.
AB  - BACKGROUND: Cordyceps cicadae is a medicinal fungus that is often used for
      treating cancer. However, the anticancer mechanisms of C. cicadae are largely
      unknown. This study aims to investigate the anticancer mechanisms of C. cicadae
      against hepatocellular carcinoma cells in vitro using a proteomic approach.
      METHODS: Human hepatocellular carcinoma MHCC97H cells were treated with a water
      extract of C. cicadae (0, 100, 250, 500, and 1000 MUg/mL) for 48 h and harvested
      for cell viability assays. The significant differences in protein expression
      between control and C. cicadae-treated cells were analyzed by two-dimensional gel
      based proteomics coupled with matrix-assisted laser desorption ionization-time of
      flight mass spectrometry. Flow cytometry analysis was employed to investigate the
      cell cycle and cell death. The anticancer molecular mechanism was analyzed by
      whole proteome mapping. RESULTS: The water extract of C. cicadae (0, 100, 250,
      500, and 1000 MUg/mL) inhibited the growth of MHCC97H cells in a dose-dependent
      manner via G2/M phase cell cycle arrest with no evidence of apoptosis. Among the
      identified proteins with upregulated expression were dynactin subunit 2, N-myc
      downstream-regulated gene 1, heat shock protein beta-1, alpha-enolase isoform 1,
      phosphatidylinositol transfer protein, and WD repeat-containing protein 1.
      Meanwhile, the proteins with downregulated expression were 14-3-3 gamma, BUB3,
      microtubule-associated protein RP/EB family member 1, thioredoxin-like protein,
      chloride intracellular channel protein 1, ectonucleoside triphosphate
      diphosphohydrolase 5, xaa-Pro dipeptidase, enoyl-CoA delta isomerase 1, protein
      disulfide isomerase-related chaperone Erp29, hnRNP 2H9B, peroxiredoxin 1, WD-40
      repeat protein, and serine/threonine kinase receptor-associated protein.
      CONCLUSION: The water extract of C. cicadae reduced the growth of human
      hepatocellular carcinoma MHCC97H cells via G2/M cell cycle arrest.

PMID- 24872844
TI  - ChIP-less analysis of chromatin states.
AB  - BACKGROUND: Histone post-translational modifications (PTMs) are key epigenetic
      regulators in chromatin-based processes. Increasing evidence suggests that vast
      combinations of PTMs exist within chromatin histones. These complex patterns,
      rather than individual PTMs, are thought to define functional chromatin states.
      However, the ability to interrogate combinatorial histone PTM patterns at the
      nucleosome level has been limited by the lack of direct molecular tools. RESULTS:
      Here we demonstrate an efficient, quantitative, antibody-free, chromatin
      immunoprecipitation-less (ChIP-less) method for interrogating diverse epigenetic
      states. At the heart of the workflow are recombinant chromatin reader domains,
      which target distinct chromatin states with combinatorial PTM patterns. Utilizing
      a newly designed combinatorial histone peptide microarray, we showed that three
      reader domains (ATRX-ADD, ING2-PHD and AIRE-PHD) displayed greater specificity
      towards combinatorial PTM patterns than corresponding commercial histone
      antibodies. Such specific recognitions were employed to develop a chromatin
      reader-based affinity enrichment platform (matrix-assisted reader chromatin
      capture, or MARCC). We successfully applied the reader-based platform to capture
      unique chromatin states, which were quantitatively profiled by mass spectrometry
      to reveal interconnections between nucleosomal histone PTMs. Specifically, a
      highly enriched signature that harbored H3K4me0, H3K9me2/3, H3K79me0 and
      H4K20me2/3 within the same nucleosome was identified from chromatin enriched by
      ATRX-ADD. This newly reported PTM combination was enriched in heterochromatin, as
      revealed by the associated DNA. CONCLUSIONS: Our results suggest the broad
      utility of recombinant reader domains as an enrichment tool specific to
      combinatorial PTM patterns, which are difficult to probe directly by antibody
      based approaches. The reader affinity platform is compatible with several
      downstream analyses to investigate the physical coexistence of nucleosomal PTM
      states associated with specific genomic loci. Collectively, the reader-based
      workflow will greatly facilitate our understanding of how distinct chromatin
      states and reader domains function in gene regulatory mechanisms.

PMID- 24872845
TI  - Preoperative HE4 and ROMA values do not improve the CA125 diagnostic value for
      borderline tumors of the ovary (BOT) - a study of the TOC Consortium.
AB  - BACKGROUND: Borderline tumors of the ovary (BOT) are a distinct entity of ovarian
      tumors, characterized by lack of stromal invasion. Recent studies postulated that
      the presence of invasive implants, incomplete staging, fertility sparing surgery
      and residual tumor after surgery are major prognostic factors for BOT. There are
      no biomarkers that can predict BOT or the presence of invasive implants.
      OBJECTIVE: The aim of our study was to assess the value of CA125 and HE4 alone,
      or within ROMA score for detecting BOT, and for predicting the presence of
      invasive implants. METHODS: Retrospective, monocentric study on 167 women
      diagnosed with BOT or benign ovarian masses. Serum HE4, CA125 levels and ROMA
      were assessed preoperatively. Due to low number of BOT with invasive implants, we
      performed an unmatched analysis (consecutive patients) and a matched analysis
      (according to age and histology) to compare BOT with invasive implants, BOT
      without invasive implants and benign disease. RESULTS: There were no significant
      differences in the HE4 and CA125 expressions in the three groups of patients (p =
      0.984 and p = 0.141, respectively). The ROC analysis showed that CA125 alone is
      superior to ROMA and HE4 in discriminating patients with BOT with invasive
      implants from patients with benign diseases and BOT without invasive implants. A
      newly established score, ROMABOT, did not perform better than ROMA. The analysis
      of the matched groups revealed similar results as the analysis of all samples.
      CONCLUSIONS: Both HE4 and CA125 are not reliable biomarkers for the diagnosis of
      BOT or for predicting the presence of invasive implants.

PMID- 24872847
TI  - Retraction: Historical facts of screening and diagnosing diabetes in pregnancy.

PMID- 24872846
TI  - Pregnancy outcome in severe OHSS patients following ascitic/plerural fluid
      drainage.
AB  - BACKGROUND: Various inflammatory cytokines have been implicated in the
      pathophysiology of severe ovarian hyperstimulation syndrome, as well as, various
      pregnancy complications, including preterm labor, pregnancy induced
      hypertension/preeclampsia and intra-uterine growth restriction. We aim to
      determine whether severe OHSS, complicated by third space fluid accumulation
      necessitating drainage, is associated with increased risk of late obstetrics
      complications. METHODS: We assessed the obstetrics and neonatal outcome measures
      of 16 patients admitted to our gynecology ward during a 6-year period, with
      severe OHSS complicated by third space fluid accumulation necessitating drainage.
      RESULTS: Patients delivered at 37.3 +/- 5.9weeks, with a mean birth weight of
      3062 +/- 757 gr. There was no single case of gestational diabetes, hypertensive
      diseases of pregnancy, nor placental abruption. Two (12.5%) patients had preterm
      delivery: one at 23 weeks' gestation and one at 28 weeks' gestation following
      preterm premature rupture of membrane. Another patient experienced an unexplained
      antepartum fetal death at 27 weeks' gestation. CONCLUSIONS: Severe OHSS,
      complicated by third space fluid sequestration necessitating drainage, is not
      associated with adverse late pregnancy outcome, except probably for preterm
      labor. Following resolution of the OHSS, pregnancies should be regarded as any
      pregnancy resulting from IVF treatment, with special attention to prevent preterm
      labor.

PMID- 24872848
TI  - Retraction: Low birth weight: causes and consequences.

PMID- 24872849
TI  - Epicardial adipose tissue thickness and plasma homocysteine in patients with
      metabolic syndrome and normal coronary arteries.
AB  - BACKGROUND: Increased epicardial adipose tissue thickness and plasma homocysteine
      levels are associated with Metabolic Syndrome (MS) and coronary artery disease.
      The majority of patients with MS have subclinical or manifest coronary artery
      disease. The aim of this study was to evaluate the relationship between MS and
      plasma homocysteine levels and epicardial adipose tissue thickness in subjects
      without epicardial coronary artery disease. METHODS: Patients who underwent
      coronary angiography due to angina or equivocal symptoms and/or abnormal stress
      test results and were found to have normal coronary arteries were evaluated for
      the presence of MS. The study group comprised 75 patients with normal coronary
      arteries and MS, and the control group included 75 age-gender matched subjects
      without coronary artery disease or MS. RESULTS: Epicardial adipose tissue
      thickness (5.8 +/- 1.9 mm vs. 4.3 +/- 1.6 mm, p <0.001) and plasma homocysteine
      levels (21.6 +/- 6.1 MUmol/L vs. 15.1 +/- 5.8 MUmol/L, p <0.001) were
      significantly higher in the MS group. Body mass index, triglyceride level,
      weight, age and waist circumference were positively and HDL cholesterol level
      were negatively correlated with both epicardial adipose tissue thickness and
      plasma homocysteine level. Epicardial adipose tissue thickness had the strongest
      correlation with plasma homocysteine level (r = 0.584, p < 0.001). For each 1 mm
      increase in epicardial adipose tissue thickness, an increase of 3.51 MUmol/L (95%
      CI: 2.24-4.79) in plasma homocysteine level was expected. CONCLUSIONS: We
      observed a close relationship between MS and epicardial adipose tissue thickness
      and plasma homocysteine levels, even in the absence of overt coronary artery
      disease.

PMID- 24872850
TI  - Medical students and research: Is there a current discrepancy between education
      and demands?
AB  - This article refers to a correspondence letter recently published in The Lancet,
      describing successful student-led research initiatives in Latin America, which
      were introduced because of low support from universities and governments. As a
      final-year medical student with keen interest in science, the topic of student
      engagement in research activities caught my interest. Literature shows that while
      junior doctors are required to perform research on their own and face intense
      pressure to publish, formal training in principles of research and scientific
      writing is often neglected by medical schools. This contrast is worrying, as the
      progression of the medical profession and the quality of patient care depend on
      high-quality research and on future generations of physician-scientists being
      both enthusiastic and competent. Hence, this article summarizes suggestions to
      increase both students' research proficiency and participation in scientific
      activities, and offers a critical view on this important topic, as medical
      schools without curricular research education and without active student
      integration should urgently consider revising their policies. 

PMID- 24872851
TI  - Psychosocial aspects of donation and the dissection course: An extra-curricular
      program with the objective of assisting students confront issues surrounding
      gross anatomy lab.
AB  - BACKGROUND AND AIM: The dissection course is an essential part of preclinical
      medical education. At the Medical Faculty of Duesseldorf, an education concept
      has been developed with the aim, to reflect with students their experiences and
      to support them in dealing with the donor and preparation. The aim of this paper
      is to present the concept. METHOD: The education concept had a peer group
      approach. It comprised a lecture, a small group seminar and an online diary as
      core element. Finally, the concept was evaluated. RESULTS: Approximately one
      sixth of students made use of the online diary. Selected entries are presented
      here. Also, one sixth of students took part in the evaluation. They rated the
      activity as helpful to prepare for the dissection course. DISCUSSION: The
      education concept could be a corner stone of a longitudinal training to promote
      the adequate encounter with topics such as dying and death.

PMID- 24872852
TI  - The FacharztDuell: innovative career counselling in medicine.
AB  - OBJECTIVE: The selection of a future medical specialty is a challenge all medical
      students face during the course of their studies. Students can choose from more
      than sixty specialties after graduation. There is usually no structured career
      counselling program available at German medical faculties. So far only little
      data on acceptance, formats and effects of different career counselling programs
      are available. The aim of this study is to describe an innovative format of
      career counselling for medical students including its evaluation of acceptance
      and its possible influence on medical specialty preferences. METHODS: The need
      for career counselling became evident after the analysis of mentor-mentee
      conversations held within the mentoring program of our medical faculty, an online
      based survey, an ad-hoc focus group and a pilot event. Panel discussions as an
      interactive format of presenting related medical specialties were developed and
      hence held four times under the name "FacharztDuell". Students evaluated all
      events separately with a questionnaire and changes in medical specialty choice
      preferences were documented using an Audience-Response-System (ARS). The
      FacharztDuell is organized regularly and supported by faculty teaching funds.
      RESULTS: Among the student body FacharztDuell was well accepted (an average of
      300 participants/event) and rated (average grade of 1.8 (SD= 0.7, 1=very good,
      6=unsatisfactory, n=424). On average, 77.8% of the participating students
      considered the FacharztDuell to be a decision support for their future selection
      of a specialty. Up to 12% of the students changed their medical specialty choice
      preference throughout the event. CONCLUSION: FacharztDuell was well accepted by
      medical students of all semesters and seems to be supportive for their selection
      of a future medical specialty. However, longitudinal studies are necessary to
      better understand the decision making process of medical students along their
      career path. The FacharztDuell is easily transferrable to other faculties with
      respect to organization, staff and technical resources.

PMID- 24872853
TI  - Designing post-graduate Master's degree programs: the advanced training program
      in Dental Functional Analysis and Therapy as one example.
AB  - INTRODUCTION: The decision to consolidate European higher education was reached
      by the Bologna Conference. Based on the Anglo-American system, a two-cycle degree
      program (Bachelor and Master) has been introduced. Subjects culminating in a
      state examination, such as Medicine and Dentistry, were excluded from this
      reform. Since the state examination is already comparable in its caliber to a
      Master's degree in Medicine or Dentistry, only advanced Master's degree programs
      with post-graduate specializations come into consideration for these subjects. In
      the field of dentistry numerous post-graduate study programs are increasingly
      coming into existence. Many different models and approaches are being pursued.
      METHOD: Since the 2004-2005 winter semester, the University of Greifswald has
      offered the Master's degree program in Dental Functional Analysis and Therapy.
      Two and a half years in duration, this program is structured to allow program
      participation while working and targets licensed dentists who wish to attain
      certified skills for the future in state-of-the-art functional analysis and
      therapy. AIM: The design of this post-graduate program and the initial results of
      the evaluation by alumni are presented here. CONCLUSION: Our experiences show
      that the conceptual idea of an advanced Master's program has proved successful.
      The program covers a specialty which leads to increased confidence in handling
      challenging patient cases. The sharing of experiences among colleagues was
      evaluated as being especially important.

PMID- 24872854
TI  - Introducing a curricular program culminating in a certificate for training peer
      tutors in medical education.
AB  - AIM: Student tutorials are now firmly anchored in medical education. However, to
      date there have only been isolated efforts to establish structured teacher
      training for peer tutors in medicine. To close this gap, a centralized tutor
      training program for students, culminating in an academic certificate, was
      implemented at Heidelberg University Medical School. The program also counts
      within the scope of the post-graduate Baden-Wurttemberg Certificate in Academic
      Teaching (Baden-Wurttemberg Zertifikat fur Hochschuldidaktik). METHOD: Based on a
      needs assessment, a modular program comprised of four modules and a total of 200
      curricular units was developed in cooperation with the Department for Key
      Competencies and Higher Education at Heidelberg University and implemented during
      the 2010 summer semester. This program covers not only topic-specific training
      sessions, but also independent teaching and an integrated evaluation of the
      learning process that is communicated to the graduates in the form of structured
      feedback. In addition, to evaluate the overall concept, semi-structured
      interviews (N=18) were conducted with the program graduates. RESULTS: To date,
      495 tutors have been trained in the basic module on teaching medicine, which is
      rated with a mean overall grade of 1.7 (SW: 0.6) and has served as Module I of
      the program since 2010. A total of 17% (N=83) of these tutors have gone on to
      enroll in the subsequent training modules of the program; 27 of them (m=12, f=15)
      have already successfully completed them. Based on qualitative analyses, it is
      evident that the training program certificate and its applicability toward the
      advanced teacher training for university instructors pose a major incentive for
      the graduates. For successful program realization, central coordination,
      extensive coordination within the medical school, and the evaluation of the
      attained skills have proven to be of particular importance. CONCLUSION: The
      training program contributes sustainably to both quality assurance and
      professionalism, as well as to solving the issue of resources in medical
      education. The introduction and continued development of similar programs is
      desirable.

PMID- 24872855
TI  - Setting up a veterinary medicine skills lab in Germany.
AB  - The amendments introduced to the current Veterinary Licensing Ordinance (TAppV)
      by the Veterinary Licensing Regulation (TAppO) have brought a high degree of
      skills orientation to fill the gap between academic study and preparing for a
      wide range of professional skills. In order to improve the veterinary skills of
      students while conveying fundamental methods in a structured and reproducible
      way, the University of Veterinary Medicine Hannover, Foundation, has set up the
      first central veterinary skills lab in Germany. Practical training is provided by
      means of a three-tier delivery approach. This involves around 40 simulators on an
      area of approx. 800 m(2) under the guidance of 6-8 staff members, along with
      supplementary resources such as posters, text instructions and YouTube videos.
      Since it opened in March 2013, there have been 769 visits to the skills lab and
      30,734 hits on YouTube. Initial results show that the skills lab helps to
      maintain student motivation by teaching them practical skills at an early stage
      of the basic study-based acquisition of knowledge, whilst reinforcing skills
      acquisition per se in competence-based teaching. It enables veterinary students
      to prepare for their first examinations and treatments of live patients in a
      manner compliant with animal welfare.

PMID- 24872856
TI  - Predictive value of the school-leaving grade and prognosis of different admission
      groups for academic performance and continuity in the medical course - a
      longitudinal study.
AB  - BACKGROUND: The school-leaving GPA and the time since completion of secondary
      education are the major criteria for admission to German medical schools.
      However, the predictive value of the school-leaving grade and the admission delay
      have not been thoroughly examined since the amendment of the Medical Licensing
      Regulations and the introduction of reformed curricula in 2002. Detailed
      information on the prognosis of the different admission groups is also missing.
      AIM: To examine the predictive values of the school-leaving grade and the age at
      enrolment for academic performance and continuity throughout the reformed medical
      course. METHODS: The study includes the central admission groups "GPA-best" and
      "delayed admission" as well as the primary and secondary local admission groups
      of three consecutive cohorts. The relationship between the criteria academic
      performance and continuity and the predictors school-leaving GPA, enrolment age,
      and admission group affiliation were examined up to the beginning of the final
      clerkship year. RESULTS: The academic performance and the prolongation of the pre
      clinical part of undergraduate training were significantly related to the school
      leaving GPA. Conversely, the dropout rate was related to age at enrolment. The
      students of the GPA-best group and the primary local admission group performed
      best and had the lowest dropout rates. The students of the delayed admission
      group and secondary local admission group performed significantly worse. More
      than 20% of these students dropped out within the pre-clinical course, half of
      them due to poor academic performance. However, the academic performance of all
      of the admission groups was highly variable and only about 35% of the students of
      each group reached the final clerkship year within the regular time. DISCUSSION:
      The school-leaving grade and age appear to have different prognostic implications
      for academic performance and continuity. Both factors have consequences for the
      delayed admission group. The academic prognosis of the secondary local admission
      group is as problematic as that of the delayed admission group. Additional
      admission instruments would be necessary, in order to recognise potentially able
      applicants independently of their school-leaving grade and to avoid the secondary
      admission procedure.

PMID- 24872857
TI  - Prediction of practical performance in preclinical laboratory courses - the
      return of wire bending for admission of dental students in Hamburg.
AB  - Although some recent studies concluded that dexterity is not a reliable predictor
      of performance in preclinical laboratory courses in dentistry, they could not
      disprove earlier findings which confirmed the worth of manual dexterity tests in
      dental admission. We developed a wire bending test (HAM-Man) which was
      administered during dental freshmen's first week in 2008, 2009, and 2010. The
      purpose of our study was to evaluate if the HAM-Man is a useful selection
      criterion additional to the high school grade point average (GPA) in dental
      admission. Regression analysis revealed that GPA only accounted for a maximum of
      9% of students' performance in preclinical laboratory courses, in six out of
      eight models the explained variance was below 2%. The HAM-Man incrementally
      explained up to 20.5% of preclinical practical performance over GPA. In line with
      findings from earlier studies the HAM-Man test of manual dexterity showed
      satisfactory incremental validity. While GPA has a focus on cognitive abilities,
      the HAM-Man reflects learning of unfamiliar psychomotor skills, spatial
      relationships, and dental techniques needed in preclinical laboratory courses.
      The wire bending test HAM-Man is a valuable additional selection instrument for
      applicants of dental schools.

PMID- 24872858
TI  - Do different medical curricula influence self-assessed clinical thinking of
      students?
AB  - OBJECTIVES: As a fundamental element of medical practice, clinical reasoning
      should be cultivated in courses of study in human medicine. To date, however, no
      conclusive evidence has been offered as to what forms of teaching and learning
      are most effective in achieving this goal. The Diagnostic Thinking Inventory
      (DTI) was developed as a means of measuring knowledge-unrelated components of
      clinical reasoning. The present pilot study examines the adequacy of this
      instrument in measuring differences in the clinical reasoning of students in
      varying stages of education in three curricula of medical studies. METHODS: The
      Diagnostic Thinking Inventory (DTI) comprises 41 items in two subscales
      ("Flexibility in Thinking" and "Structure of Knowledge in Memory"). Each item
      contains a statement or finding concerning clinical reasoning in the form of a
      stem under which a 6-point scale presents opposing conclusions. The subjects are
      asked to assess their clinical thinking within this range. The German-language
      version of the DTI was completed by 247 student volunteers from three schools and
      varying clinical semesters. In a quasi-experimental design, 219 subjects from
      traditional and model courses of study in the German state of North Rhine
      Westphalia took part. Specifically, these were 5(th), 6(th) and 8(th) semester
      students from the model course of study at Witten/Herdecke University (W/HU),
      from the model (7(th) and 9(th) semester) and traditional (7(th) semester)
      courses of study at the Ruhr University Bochum (RUB) and from the model course of
      study (9(th) semester) at the University of Cologne (UoC). The data retrieved
      were quantitatively assessed. RESULTS: The reliability of the questionnaire in
      its entirety was good (Cronbach's alpha between 0.71 and 0.83); the reliability
      of the subscales ranged between 0.49 and 0.75. The different groups were compared
      using the Mann-Whitney test, revealing significant differences among semester
      cohorts within a school as well as between students from similar academic years
      in different schools. Among the participants from the model course of study at
      the W/HU, scores increased from the 5(th) to the 6(th) semester and from the
      5(th) to the 9(th) semester. Among individual cohorts at RUB, no differences
      could be established between model and traditional courses of study or between
      7(th) and 9(th) semester students in model courses of study. Comparing all
      participating highest semester students, the 8(th) semester participants from the
      W/HU achieved the highest scores - significantly higher than those of 9(th)
      semester RUB students or 9(th) semester UoC students. Scores from the RUB 9(th)
      semester participants were significantly higher than those of the 9(th) semester
      UoC participants. DISCUSSION: The German-language version of the DTI measures
      self-assessed differences in diagnostic reasoning among students from various
      semesters and different model and traditional courses of study with satisfactory
      reliability. The results can be used for discussion in the context of diverse
      curricula. The DTI is therefore appropriate for further research that can then be
      correlated with the different teaching method characteristics and outcomes of
      various curricula.

PMID- 24872859
TI  - Thinking and acting scientifically: Indispensable basis of medical education.

PMID- 24872860
TI  - Fracture prevalence during an unusual period of snow and ice in the Netherlands.
AB  - BACKGROUND: The objective of the current study was to assess the effect of an
      unusual 10-day snow and ice period on the prevalence of fractures in an emergency
      department (ED) in the Netherlands. Furthermore, patients with fractures during
      the snow and ice period were compared to those in the control period with respect
      to gender, age, location of accident, length of stay, disposition, and anatomical
      site of the injury. METHODS: Fracture prevalence during a 10-day study period
      with snow and ice (January 14, 2013 until January 23, 2013) was compared to a
      similar 10-day control period without snow or ice (January 16, 2012 until January
      25, 2012). The records of all patients with a fracture were manually selected.
      Besides this, basic demographics, type of fracture, and location of the accident
      (inside or outside) were compared. RESULTS: A total of 1,785 patients visited the
      ED during the study period and 1,974 during the control period. A fracture was
      found in 224 patients during the study period and in 109 patients during the
      control period (P <0.01). More fractures sustained outside account for this
      difference. No differences were found in gender, mean age, and length of ED stay.
      However, during the snow and ice period the percentage of fractures in the middle
      aged (31-60 yrs) was significantly higher than in the control period (P <0.01).
      CONCLUSIONS: The number of fractures sustained more than doubled during a period
      with snow and ice as compared to the control period. In contrast to other studies
      outside the Netherlands, not the elderly, but the middle-aged were most affected
      by the slippery conditions.

PMID- 24872861
TI  - Motor function and perception in children with neuropsychiatric and conduct
      problems: results from a population based twin study.
AB  - BACKGROUND: Children with early symptomatic psychiatric disorders such as
      Attention-Deficit/Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder
      (ASD) have been found to have high rates of motor and/or perception difficulties.
      However, there have been few large-scale studies reporting on the association
      between Conduct Disorder (CD) and motor/perception functions. The aim of the
      present study was to investigate how motor function and perception relate to
      measures of ADHD, ASD, and CD. METHODS: Parents of 16,994 Swedish twins (ages
      nine and twelve years) were interviewed using the Autism-Tics, ADHD and other
      Comorbidities inventory (A-TAC), which has been validated as a screening
      instrument for early onset child psychiatric disorders and symptoms. Associations
      between categorical variables of scoring above previously validated cut-off
      values for diagnosing ADHD, ASD, and CD on the one hand and motor and/or
      perception problems on the other hand were analysed using cross-tabulations, and
      the Fisher exact test. Associations between the continuous scores for ADHD, ASD,
      CD, and the subdomains Concentration/Attention, Impulsiveness/Activity,
      Flexibility, Social Interaction and Language, and the categorical factors age and
      gender, on the one hand, and the dependent dichotomic variables Motor control and
      Perception problems, on the other hand, were analysed using binary logistic
      regression in general estimated equation models. RESULTS: Male gender was
      associated with increased risk of Motor control and/or Perception problems.
      Children scoring above the cut-off for ADHD, ASD, and/or CD, but not those who
      were 'CD positive' but 'ADHD/ASD negative', had more Motor control and/or
      Perception problems, compared with children who were screen-negative for all
      three diagnoses. In the multivariable model, CD and Impulsiveness/Activity had no
      positive associations with Motor control and/or Perception problems. CONCLUSIONS:
      CD symptoms or problems with Impulsiveness/Activity were associated with Motor
      control or Perception problems only in the presence of ASD symptoms and/or
      symptoms of inattention. Our results indicate that children with CD but without
      ASD or inattention do not show a deviant development of motor and perceptual
      functions. Therefore, all children with CD should be examined concerning motor
      control and perception. If problems are present, a suspicion of ADHD and/or ASD
      should be raised.

PMID- 24872862
TI  - Prior adversities predict posttraumatic stress reactions in adolescents following
      the Oslo Terror events 2011.
AB  - BACKGROUND: Former studies suggest that prior exposure to adverse experiences
      such as violence or sexual abuse increases vulnerability to posttraumatic stress
      reactions in victims of subsequent trauma. However, little is known about how
      such a history affects responses to terror in the general adolescent population.
      OBJECTIVE: To explore the role of prior exposure to adverse experiences as risk
      factors for posttraumatic stress reactions to the Oslo Terror events. METHOD: We
      used data from 10,220 high school students in a large cross-sectional survey of
      adolescents in Norway that took place seven months after the Oslo Terror events.
      Prior exposure assessed was: direct exposure to violence, witnessing of violence,
      and unwanted sexual acts. We explored how these prior adversities interact with
      well-established risk factors such as proximity to the events, perceived life
      threat during the terror events, and gender. RESULTS: All types of prior exposure
      as well as the other risk factors were associated with terror-related
      posttraumatic stress reactions. The effects of prior adversities were, although
      small, independent of adolescents' proximity to the terror events. Among prior
      adversities, only the effect of direct exposure to violence was moderated by
      perceived life threat. Exposure to prior adversities increased the risk of
      posttraumatic stress reactions equally for both genders, but proximity to the
      terror events and perceived life threat increased the risk more in females.
      CONCLUSIONS: Terror events can have a more destabilizing impact on victims of
      prior adversities, independent of their level of exposure. The findings may be
      relevant to mental health workers and others providing post-trauma health care.

PMID- 24872863
TI  - Employment of the Triple Helix concept for development of regenerative medicine
      applications based on human pluripotent stem cells.
AB  - Using human pluripotent stem cells as a source to generate differentiated
      progenies for regenerative medicine applications has attracted substantial
      interest during recent years. Having the capability to produce large quantities
      of human cells that can replace damaged tissue due to disease or injury opens
      novel avenues for relieving symptoms and also potentially offers cures for many
      severe human diseases. Although tremendous advancements have been made, there is
      still much research and development left before human pluripotent stem cell
      derived products can be made available for cell therapy applications. In order to
      speed up the development processes, we argue strongly in favor of cross
      disciplinary collaborative efforts which have many advantages, especially in a
      relatively new field such as regenerative medicine based on human pluripotent
      stem cells. In this review, we aim to illustrate how some of the hurdles for
      bringing human pluripotent stem cell derivatives from bench-to-bed can be
      effectively addressed through the establishment of collaborative programs
      involving academic institutions, biotech industries, and pharmaceutical
      companies. By taking advantage of the strengths from each organization,
      innovation and productivity can be maximized from a resource perspective and
      thus, the chances of successfully bringing novel regenerative medicine treatment
      options to patients increase. 

PMID- 24872866
TI  - Characteristics of Colorectal Cancer in Khorramabad, Iran during 2013.
AB  - BACKGROUND Colorectal cancer is a common, deadly disease with different incidence
      rates in different parts of the world. The present study aims to investigate the
      clinical presentations, colonoscopic findings, and family history of colorectal
      cancer in the city of Khorramabad, Iran. METHODS This cross-sectional study,
      conducted in 2013, included 112 patients diagnosed with colorectal cancer by
      colonoscopy with pathological confirmation in addition to 112 individuals matched
      with patients for age and gender. Controls were chosen from the outpatients
      admitted to the Skin and Eye Clinics of ShohadaAshayer Hospital in Khorramabad
      who had no gastrointestinal diseases. A self-generated questionnaire was used to
      assess family history of smoking and gastrointestinal cancer history in immediate
      relatives of subjects from both groups. Fisher's exact test and odds ratios (OR)
      were used to analyze the data. RESULTS Based on the findings of this study, the
      most common clinical presentation in the patients was abdominal pain (67.9%). The
      sigmoid colon (40%) was the most common anatomical site of the tumor in men; the
      rectum (34.6%) and sigmoid colon (34.6%) were the most common sites in women,
      which was not statistically significant (p=0.21). There were 11 (19.6%) patients
      and 2 (3.6%) individuals in the control group who reported a history of
      colorectal cancer in their immediate relatives, which was statistically
      significant (p=0.008). CONCLUSION In this study, left-sided colon cancer was more
      common. Subjects with colon cancer had more positive FHx. This indicated that
      genetic factors, in addition to environmental factors, could increase the
      incidence of colorectal cancer in a community. A better identification of these
      factors would result in better control and management of this disease. 

PMID- 24872865
TI  - Gastroesophageal Reflux Disease and overall and Cause-specific Mortality: A
      Prospective Study of 50000 Individuals.
AB  - BACKGROUND Only a few studies in Western countries have investigated the
      association between gastroesophageal reflux disease (GERD) and mortality at the
      general population level and they have shown mixed results. This study
      investigated the association between GERD symptoms and overall and cause-specific
      mortality in a large prospective population-based study in Golestan Province,
      Iran. METHODS Baseline data on frequency, onset time, and patient-perceived
      severity of GERD symptoms were available for 50001 participants in the Golestan
      Cohort Study (GCS). We identified 3107 deaths (including 1146 circulatory and 470
      cancer-related) with an average follow-up of 6.4 years and calculated hazard
      ratios (HR) and 95% confidence intervals (CI) adjusted for multiple potential
      confounders. RESULTS Severe daily symptoms (defined as symptoms interfering with
      daily work or causing nighttime awakenings on a daily bases, reported by 4.3% of
      participants) were associated with cancer mortality (HR 1.48, 95% CI: 1.04-2.05).
      This increase was too small to noticeably affect overall mortality. Mortality was
      not associated with onset time or frequency of GERD and was not increased with
      mild to moderate symptoms. CONCLUSION We have observed an association with GERD
      and increased cancer mortality in a small group of individuals that had severe
      symptoms. Most patients with mild to moderate GERD can be re-assured that their
      symptoms are not associated with increased mortality. 

PMID- 24872864
TI  - Adult Hepatic Progenitor Cell Niche: How it affects the Progenitor Cell Fate.
AB  - The hepatic progenitor cell (HPC) niche is a special microenvironment composed of
      different cell types, extracellular matrix (ECM) components, growth factors and
      cytokines released by the niche cells that help to maintain the characteristics
      of HPCs and the balance between their activation, proliferation and
      differentiation. Composition of this special microenvironment, created in
      response to specific liver damage, together with critical interactions between
      different partners of the HPC niche can determine the fate decision and
      differentiation pathways of HPCs. A number of recent studies have shed light on
      factors and signals from the HPC niche that determines the choice of HPCs
      differentiation towards a specific cell type depending on the nature of the liver
      injury and resultant microenvironment created by this injury. This paper seeks to
      provide an in-depth review, through a literature review and the authors'
      experiences, of the most recent findings on the role of the HPC niche in fate
      choice option of HPCs toward either hepatocytes or bile duct epithelial cells and
      its clinical relevance. 

PMID- 24872867
TI  - Juvenile Hemochromatosis, Genetic Study and Long-term Follow up after Therapy.
AB  - BACKGROUND Hereditary hemochromatosis (HH) is a very rare disease in Iran and
      reported cases are all negative for HFE mutation. We report a family affected by
      severe juvenile hemochromatosis (JH) with a detailed molecular study of the
      family members. METHODS We studied a pedigree with siblings affected by juvenile
      HH and followed them for 3 years. Microsatellite and gene sequencing analysis was
      performed for all family members. RESULTS Two siblings (the proband and his
      sister, aged 26 and 30 years, respectively) were found to have clinical findings
      of JH. The proband's brother, who presented with hyperpigmentation, died of
      probable JH at the age of 24 years. Gene sequencing analysis showed that the
      proband has a homozygote c.265T>C (p.C89R) HJV mutation + a heterozygote c.884T>C
      (p.V295A) mutation of HFE. The affected proband's sister presented with the same
      HJV c.265T>C (p.C89R) homozygote mutation. In addition, we found the HJV c.98
      6C>G polymorphic variant in both the sister and proband (homozygote). Sequencing
      of hepcidin (HAMP), TfR2, and FPN revealed no mutation. CONCLUSION We have shown
      that molecular analysis of the HH related gene is a powerful tool for reliable
      diagnosis of JH and, in conjunction with magnetic resonance imaging (MRI) and
      noninvasive liver stiffness measurement by elastography, is adequate tool for
      management and follow up of HH. 

PMID- 24872868
TI  - The clinical presentation of celiac disease: experiences from northeastern iran.
AB  - BACKGROUND This study aimed to explore demographic characteristics and clinical
      presentations of celiac disease (CD) in Northeastern Iran. METHODS This was a
      cross-sectional retrospective study of 193 adults with CD who presented to
      Mashhad University Gastroenterology Clinic between 2008 and 2013. Patient data
      that included mode of presentation and the presence of any concomitant illnesses
      were collected. Intestinal biopsy and serum anti-tissue transglutaminase (anti
      tTG) were used for diagnosis. Mucosal lesions were classified according to
      modified Marsh classification. RESULTS Overall, 132 females and 61 males, with a
      mean age at diagnosis of 32.6 +/- 13.2 years were included. The patient's chief
      complaints in order of decreasing frequency were dyspepsia (24.6%), diarrhea
      (20%), anemia (12.8%), and flatulence (7.2%). Bone disease was seen (osteopenia,
      osteoporosis) in 30% of patients. A positive family history of CD was found in
      17.9% of cases. There were 64% who had serum anti-tTG >200 units/ml and 78% had a
      Marsh classification grade 3 on duodenal biopsy. The histology grade (Marsh) did
      not show any correlation with anti-tTG serum levels, age, body mass index (BMI)
      or hemoglobin levels. CONCLUSION In Northeastern Iran, CD was seen more commonly
      in females and with non-diarrheal presentations. Abdominal discomfort, anemia and
      bone disease were most common primary presentations in this area. Histology grade
      showed no significant correlation with level of anti-tTG, BMI or hemoglobin
      levels. We suggest screening for CD in unexplained abdominal discomfort, bone
      disease and anemia. 

PMID- 24872869
TI  - Epidemiologic and demographic survey of celiac disease in khuzestan province.
AB  - BACKGROUND Celiac disease presents with a wide spectrum of symptoms. This study
      clarifies different aspects of celiac disease along with the most common patterns
      of celiac presentation in Khuzestan Province, Iran. METHODS Patients' information
      was obtained by evaluation of their files from the archives of the Khuzestan
      Celiac Society and records at gastroenterologists' offices in this province.
      RESULTS Overall, there were 103 (40 males, 63 females) patients included in this
      study. Patients' mean ages were 33 +/- 11 years (males) and 31.6 +/- 11.7 years
      (females). In terms of geographic distribution, 54.1% resided in the center of
      the province followed by 26.5% who were residents of the northern area. The rate
      of employment among men was 70.6% whereas it was 8.3% for women. In terms of
      education, 21.9% of men and 33.3% of women had academic educations. The rate of
      matrimony was 80.6% (n=29) for men, 65.4% (n=38) for women and 3.4% (n=2) who
      were divorced. Mean height was 164 +/- 14 cm in men and 157.5 +/- 10 cm in women.
      Mean BMI at the time of presentation was 22.7 in men and 22.6 in women. The most
      common gastrointestinal (GI) complaints in male patients were diarrhea (35%),
      reflux (20%), bloating (17.5%), abdominal pain (15%), vomiting (15%) and
      constipation (7.5%). Female patients experienced diarrhea (49.2%), abdominal pain
      (31.7%), bloating (31.7%), vomiting (19%), constipation(9.5%) and reflux (7.9%).
      The most common concomitant non-GI disorders among male patients were anemia
      (17.1%), thyroid disease (14.3%), and weight loss (14.3%); women experienced
      anemia (33.9%), thyroid disease (12.5%), and weight loss (7.1%). Approximately
      half of the patients exhibited symptoms for more than five years prior to
      diagnosis and 90% were diagnosed by gastroenterologists. Of these, 43% had normal
      endoscopy results. The most common serologic markers were anti-TTG (69.9%), anti
      EMA (27.7%). CONCLUSION Physicians, prior to attributing patients' symptoms to
      irritable bowel syndrome (IBS), should be aware that patients who present with
      long-term nonspecific symptoms might possibly have celiac disease. During
      endoscopy, the threshold for obtaining biopsies should be low. 

PMID- 24872870
TI  - Fulminate hepatic failure as an initial presentation of non-hodgkin lymphoma: a
      case report.
AB  - Viral hepatitis and toxins comprise most common causes of fulminate hepatic
      failure that are often diagnosed with standard laboratory tests. Herein we
      discuss a rare, difficult to diagnosis etiology of acute liver failure (ALF). A
      62-year-old man presented with a two-week history of fever and fatigue. At four
      days before admission he became lethargic. His past medical and drug histories
      were unremarkable. Physical examination revealed generalized jaundice, fever and
      loss of consciousness. Laboratory tests showed elevated liver transaminases with
      direct hyper-bilirubinemia. Abdominal ultrasonography and CT scan showed
      hepatosplenomegaly and para-aortic abdominal lymphadenopathy. A further work-up
      included liver biopsy. The histopathology and imunohistochemistry was compatible
      with diffuse large B-cell lymphoma. He underwent high dose glucocorticoid therapy
      but his condition deteriorated rapidly and he died eight days after admission.
      ALF as an initial manifestation of malignant hepatic infiltration is extremely
      rare yet should be considered in all patients with unknown hepatic failure that
      are highly suspicious for malignant neoplasm. 

PMID- 24872871
TI  - The necessity for an Iranian gut microbiome initiative.

PMID- 24872872
TI  - Estimating age-dependent per-encounter chlamydia trachomatis acquisition risk via
      a Markov-based state-transition model.
AB  - BACKGROUND: Chlamydial infection is a common bacterial sexually transmitted
      infection worldwide, caused by C. trachomatis. The screening for C. trachomatis
      has been proven to be successful. However, such success is not fully realized
      through tailoring the recommended screening strategies for different age groups.
      This is partly due to the knowledge gap in understanding how the infection is
      correlated with age. In this paper, we estimate age-dependent risks of acquiring
      C. trachomatis by adolescent women via unprotected heterosexual acts. METHODS: We
      develop a time-varying Markov state-transition model and compute the incidences
      of chlamydial infection at discrete age points by simulating the state-transition
      model with candidate per-encounter acquisition risks and sampled numbers of unit
      time unprotected coital events at different age points. We solve an optimization
      problem to identify the age-dependent estimates that offer the closest matches to
      the observed infection incidences. We also investigate the impact of
      antimicrobial treatment effectiveness on the parameter estimates and the
      differences between the acquisition risks for the first-time infections and
      repeated infections. RESULTS: Our case study supports the beliefs that age is an
      inverse predictor of C. trachomatis transmission and that protective immunity
      developed after initial infection is only partial. CONCLUSIONS: Our modeling
      method offers a flexible and expandable platform for investigating STI
      transmission.

PMID- 24872873
TI  - Mesenchymal stem cells contribute to the chemoresistance of hepatocellular
      carcinoma cells in inflammatory environment by inducing autophagy.
AB  - BACKGROUND: Mesenchymal stem cells (MSCs) have been reported to play an important
      role in tumor growth. Inflammation is an important feature of hepatocellular
      carcinoma (HCC). Certain inflammatory cytokines produced in tumor
      microenvironment modulate functional activities of MSCs. At the present time,
      however, the role of MSCs in the development of HCC cell resistance to
      chemotherapy in the inflammatory microenvironment during tumor growth has not yet
      been identified. METHODS: MTT and PI/Annexin V-FITC assay were employed to
      examine the proliferation and apoptosis of HCC cell lines. The expression of TGF
      beta are detected by Realtime PCR and Western blot. GFP tagged LC3 expression
      vector and electron microscopy are utilized to demonstrate the occurrence of
      autophagy. RESULTS: We observed that MSCs pretreated with the combination of IFN
      gamma and TNF-alpha induced resistance to chemotherapy in HCC cell lines in both
      the in vitro and in vivo circumstances. Following exposure to conditioned medium
      of MSCs that were pre-treated with IFN-gamma plus TNF-alpha, HCC cell line cells
      underwent autophagy which serves as a protective mechanism for HCC cells to
      resist the cell toxicity of chemotherapeutic agents. Treatment of HCC cell line
      cells with autophagy inhibitor effectively reversed the MSCs-induced resistance
      to chemotherapy in these cells. Stimulation with the combination of IFN-gamma and
      TNF-alpha provoked expression of TGF-beta by MSCs. MSCs-induced chemoresistance
      in HCC cell lines was correlated with the up-regulation of TGF-beta expression by
      MSCs. Knockdown of TGF-beta expression by MSCs with siRNA attenuated MSCs-induced
      chemoresistance in HCC cells. CONCLUSIONS: These results suggest that increase in
      TGF-beta expression by MSCs in the inflammatory microenvironment of HCC promotes
      the development of chemoresistance in HCC cells.

PMID- 24872874
TI  - Role of intervention programs to increase influenza vaccination in Israel.
AB  - BACKGROUND: Influenza vaccination is the most efficient and cost-effective method
      to prevent influenza. To increase vaccination coverage, health authorities use
      various intervention programs (IPs), such as cost subsidies or placing
      vaccination centers in malls to make vaccination more accessible. Nevertheless,
      vaccination coverage has been sub-optimal in most developed countries, including
      in Israel. METHODS: To determine possible drivers of individual vaccination
      uptake and to examine the effectiveness of different IPs in increasing
      vaccination, we analyzed a telephone survey of a representative sample of the
      Israeli population conducted in March 2011 (n = 470), and paper questionnaires at
      the work place and at homes during April-July 2011 to several sub-populations :
      soldiers (n = 81), medical staff (n = 107), ultra-orthodox Jews (n = 72), Israeli
      Arabs (n = 87) and students (n = 85). RESULTS: The population can be stratified
      into three sub-groups: Acceptors, who receive vaccination regardless of IPs
      (22%), Conditional Acceptors, who are only vaccinated because of IP
      implementation (44%) and Non-Acceptors, who are not vaccinated despite IP
      implementation (34%). Our analysis shows that the risk perception towards
      influenza relative to vaccination is higher in the Acceptors than in the
      Conditional Acceptors, with the Non-Acceptors showing the lowest risk perception
      (P < 0.01). For Conditional Acceptors, physician recommendation is the most
      effective IP, regardless of the sub-population tested (P = 0.04). Students and
      low-income participants were more prone than any others to be persuaded to
      receive vaccination following IPs. In addition, financial incentives were more
      effective for ultra-religious orthodox Jews and students; vaccinations in more
      accessible areas were more effective for the ultra-religious orthodox, soldiers,
      and medical personnel; and TV and radio advertisements were more effective for
      people above 50 relative to other age groups. CONCLUSIONS: Risk perception of
      influenza and vaccination governs the likelihood of successful implementation of
      IPs. Policy makers in Israel should invest efforts to increase the knowledge
      regarding influenza and vaccination, and should apply specific interventions
      customized to the preferences and diverse perceptions among the Israeli sub
      populations.

PMID- 24872875
TI  - Comparison of non-surgical treatment methods for patients with lumbar spinal
      stenosis: protocol for a randomized controlled trial.
AB  - BACKGROUND: Lumbar spinal stenosis is the most common reason for spinal surgery
      in older adults. Previous studies have shown that surgery is effective for severe
      cases of stenosis, but many patients with mild to moderate symptoms are not
      surgical candidates. These patients and their providers are seeking effective non
      surgical treatment methods to manage their symptoms; yet there is a paucity of
      comparative effectiveness research in this area. This knowledge gap has hindered
      the development of clinical practice guidelines for non-surgical treatment
      approaches for lumbar spinal stenosis. METHODS/DESIGN: This study is a
      prospective randomized controlled clinical trial that will be conducted from
      November 2013 through October 2016. The sample will consist of 180 older adults
      (>60 years) who have both an anatomic diagnosis of stenosis confirmed by
      diagnostic imaging, and signs/symptoms consistent with a clinical diagnosis of
      lumbar spinal stenosis confirmed by clinical examination. Eligible subjects will
      be randomized into one of three pragmatic treatment groups: 1) usual medical
      care; 2) individualized manual therapy and rehabilitative exercise; or 3)
      community-based group exercise. All subjects will be treated for a 6-week course
      of care. The primary subjective outcome is the Swiss Spinal Stenosis
      Questionnaire, a self-reported measure of pain/function. The primary objective
      outcome is the Self-Paced Walking Test, a measure of walking capacity. The
      secondary objective outcome will be a measurement of physical activity during
      activities of daily living, using the SenseWear Armband, a portable device to be
      worn on the upper arm for one week. The primary analysis will use linear mixed
      models to compare the main effects of each treatment group on the changes in each
      outcome measure. Secondary analyses will include a responder analysis by group
      and an exploratory analysis of potential baseline predictors of treatment
      outcome. DISCUSSION: Our study should provide evidence that helps to inform
      patients and providers about the clinical benefits of three non-surgical
      approaches to the management of lumbar spinal stenosis symptoms. TRIAL
      REGISTRATION: ClinicalTrials.gov identifier: NCT01943435.

PMID- 24872876
TI  - Comparative palatability of five supplements designed for cats suffering from
      chronic renal disease.
AB  - BACKGROUND: Intestinal phosphate binders, uremic toxin binders and some other
      types of supplements are an integral part of the management of chronic kidney
      disease (CKD) in various species, including cats. This pathology in domestic
      carnivores requires life-long nutritional and medical management. In this
      context, the compliance of owners and patients cannot be achieved without an
      adequate level of palatability for oral medication or supplementation. Knowing
      that hyporexia and anorexia are among the most commonly seen clinical signs in
      cats suffering from CKD this is already, in itself, a serious obstacle to
      acceptable compliance in sick animals. The aim of the present study was to
      investigate the palatability of four commercially available products designed for
      cats suffering from CKD: Ipakitine(r) (Vetoquinol, France), Azodyl(r)
      (Vetoquinol, USA), Renalzin(r) (Bayer, France), Rubenal(r) (Vetoquinol, France)
      and an additional recently developed product: Pronefra(r) (Virbac, France). The
      study was performed with a group of previously-characterised cats, all living in
      an enriched and well-being securing environment of an independent centre housing
      panels of pets expert in palatability measurement. In total 172 monadic testings
      were performed. The palatability of each product was assessed by measuring their
      rates of prehension and consumption, and the consumption proportions were also
      analysed. RESULTS: The most palatable presentation (based on useful consumption)
      was Pronefra(r), which was significantly higher than Azodyl(r) (p = 0.046),
      Ipakitine(r) (p < 0.0001), Renalzin(r) (p < 0.0001) and Rubenal(r) (p < 0.0001).
      The product with the highest rate of prehension was also Pronefra(r), which was
      significantly higher than Azodyl(r) (p = 0.0019), Ipakitine(r) (p = 0.0023),
      Renalzin(r) (p = 0.0008) and Rubenal(r) (p < 0.0001). CONCLUSION: Pronefra(r) was
      the most palatable presentation tested, meaning it may be useful for improving
      ease of supplementation in CKD cats.

PMID- 24872877
TI  - The 3,000 rice genomes project.
AB  - BACKGROUND: Rice, Oryza sativa L., is the staple food for half the world's
      population. By 2030, the production of rice must increase by at least 25% in
      order to keep up with global population growth and demand. Accelerated genetic
      gains in rice improvement are needed to mitigate the effects of climate change
      and loss of arable land, as well as to ensure a stable global food supply.
      FINDINGS: We resequenced a core collection of 3,000 rice accessions from 89
      countries. All 3,000 genomes had an average sequencing depth of 14*, with average
      genome coverages and mapping rates of 94.0% and 92.5%, respectively. From our
      sequencing efforts, approximately 18.9 million single nucleotide polymorphisms
      (SNPs) in rice were discovered when aligned to the reference genome of the
      temperate japonica variety, Nipponbare. Phylogenetic analyses based on SNP data
      confirmed differentiation of the O. sativa gene pool into 5 varietal groups -
      indica, aus/boro, basmati/sadri, tropical japonica and temperate japonica.
      CONCLUSIONS: Here, we report an international resequencing effort of 3,000 rice
      genomes. This data serves as a foundation for large-scale discovery of novel
      alleles for important rice phenotypes using various bioinformatics and/or genetic
      approaches. It also serves to understand the genomic diversity within O. sativa
      at a higher level of detail. With the release of the sequencing data, the project
      calls for the global rice community to take advantage of this data as a
      foundation for establishing a global, public rice genetic/genomic database and
      information platform for advancing rice breeding technology for future rice
      improvement.

PMID- 24872878
TI  - The 3,000 rice genomes project: new opportunities and challenges for future rice
      research.
AB  - Rice is the world's most important staple grown by millions of small-holder
      farmers. Sustaining rice production relies on the intelligent use of rice
      diversity. The 3,000 Rice Genomes Project is a giga-dataset of publically
      available genome sequences (averaging 14* depth of coverage) derived from 3,000
      accessions of rice with global representation of genetic and functional
      diversity. The seed of these accessions is available from the International Rice
      Genebank Collection. Together, they are an unprecedented resource for advancing
      rice science and breeding technology. Our immediate challenge now is to
      comprehensively and systematically mine this dataset to link genotypic variation
      to functional variation with the ultimate goal of creating new and sustainable
      rice varieties that can support a future world population that will approach 9.6
      billion by 2050. 

PMID- 24872879
TI  - A National Study of the Impact of Rapid Influenza Testing on Clinical Care in the
      Emergency Department.
AB  - BACKGROUND: Rapid influenza diagnostic tests (RIDT) may influence physician
      decision-making. Single-center studies suggest that influenza diagnosed in
      association with RIDT reduces ancillary testing and antibiotic prescribing. The
      extent of RIDT use in US emergency departments (EDs) and their impact on patient
      management are unknown. We examined the use of RIDT and its effect on influenza
      management, using a national sample of ED visits. METHODS: We performed a
      retrospective study using data from the National Hospital Ambulatory Medical Care
      Survey, an annually administered survey capturing a nationally representative
      sample of visits to US EDs. We identified patient visits in which RIDT was
      performed and/or influenza was diagnosed across 3 influenza seasons (2007-2009).
      Ancillary testing and antibiotic and antiviral prescribing were evaluated for 2
      groups of patients in whom RIDT was performed (those given or not given a
      diagnosis of influenza) and a third group in whom influenza was diagnosed but
      RIDT was not performed. RESULTS: Rapid influenza diagnostic tests were performed
      during 4.2 million visits. Forty-two percent of influenza diagnoses were made in
      association with RIDT. For patients diagnosed with influenza, ancillary test
      ordering was lower (45% vs 53% of visits) and there were fewer antibiotic
      prescriptions (11% vs 23%), and antiviral use was higher (56% vs 19%) when the
      diagnosis was made in association with RIDT. CONCLUSIONS: Influenza diagnoses
      made in association with RIDT resulted in fewer tests and antibiotic
      prescriptions and more frequent use of antivirals. This finding suggests that
      test results influence physician behavior.

PMID- 24872880
TI  - Age-Specific Patterns of Influenza Activity in Utah: Do Older School Age Children
      Drive the Epidemic?
AB  - Across 12 consecutive influenza seasons in Utah, medically-attended visits for
      laboratory-confirmed influenza infection peaked first among older children (12-18
      years). Peak activity in older children preceded that of children 0-4 years by
      more than 2 days and that of peak activity among adults >=65 years by more than 6
      days. 

PMID- 24872881
TI  - Effect of dietary phosphorus content on milk production and phosphorus excretion
      in dairy cows.
AB  - BACKGROUND: Phosphorus (P) supplementation is costly and can result in excess P
      excretion. This study investigated the effects of reducing dietary P on milk
      production and P excretion in dairy cows over a full lactation. METHOD: Forty
      five multiparous Holstein dairy cows were divided into 15 blocks according to
      expected calving date and previous milk yield, and assigned randomly to one of
      the three dietary treatments: 0.37, 0.47, and 0.57% P (DM basis); these P levels
      represent the NRC recommendations, Chinese recommendations, and the amount of
      dietary P commonly fed by Chinese dairy farmers, respectively. Average daily feed
      intake was calculated from monthly data on feed offered and refused. Milk yields
      of individual cows were recorded weekly, and milk samples were taken for analysis
      of protein, fat, solids-not-fat, lactose, and somatic cell count. Blood samples
      were collected on days -6, -3, 0, 3, 6 relative to calving, and then monthly
      throughout lactation, and analyzed for P and Ca concentrations. Spot samples of
      feces and urine were collected for 3 consecutive d during weeks 12, 24, and 36,
      and P concentrations were analyzed. Reproduction and health data were recorded.
      RESULTS: Dietary P did not affect dry matter intake or milk yield (P > 0.10).
      Milk fat content was slightly higher in cows fed 0.37% P than in cows fed 0.47% P
      (P = 0.05). Serum concentrations of P and Ca did not reflect dietary P content (P
      > 0.10). Fecal and urinary P both declined linearly (P < 0.05) as dietary P
      decreased from 0.57 to 0.37%. Fecal P content was 25% less when dietary P was
      0.37% compared to 0.57%. Health events and reproductive performance were not
      associated with dietary P content (P > 0.05). CONCLUSIONS: Lowering dietary P
      from 0.57 to 0.37% did not negatively affect milk production, but did
      significantly reduce P excretion into environment.

PMID- 24872882
TI  - Calcium potentiates the effect of estradiol on PGF2alpha production in the bovine
      endometrium.
AB  - BACKGROUND: Estradiol (E2) is required for luteolysis in cows and its injection
      stimulates prostaglandin F2alpha (PGF2alpha) release. The main goal of our study
      was to investigate the ability of endometrial explants and cells treated with E2
      and the calcium ionophore (CI) A23187 to synthesize PGF2alpha. RESULTS: Treatment
      with E2 in vivo resulted in a 48.4% increase of PGF2alpha production by
      endometrial explants treated in vitro with A23187. Production of PGF2alpha was
      better stimulated with A23187 at concentrations of 10(-6) and 10(-5) mol/L
      compared with other concentrations used. The concentration of PGF2alpha for
      untreated bovine endometrial cell cultures was 33.1 pg/mL, while for cultures
      treated with E2, A23187, or a combination of E2 and A23187, the PGF2alpha
      concentration was 32.5, 92.4 and 145.6 pg/mL, respectively. CONCLUSIONS:
      Treatment with A23187 tended to stimulate PGF2alpha production. In the presence
      of E2, A23187 significantly stimulated PGF2alpha synthesis. It appears that
      A23187 potentiates the effects of E2 with respect to synthesis of endometrial
      PGF2alpha in cattle.

PMID- 24872883
TI  - Is health literacy related to health behaviors and cell phone usage patterns
      among the text4baby target population?
AB  - BACKGROUND: Text4baby provides educational text messages to pregnant and
      postpartum women and targets underserved women. The primary purpose of this study
      is to examine the health behaviors and cell phone usage patterns of a text4baby
      target population and the associations with health literacy. METHODS: Pregnant
      and postpartum women were recruited from two Women, Infant and Children clinics
      in Atlanta. Women were asked about their demographics, selected pregnancy or
      postpartum health behaviors, and cell phone usage patterns. Health literacy
      skills were measured with the English version of the Newest Vital Sign.
      Multivariable logistic regression was used to examine health behaviors and cell
      usage patterns by health literacy classification, controlling for commonly
      accepted confounders. RESULTS: Four hundred sixty-eight women were recruited, and
      445 completed the Newest Vital Sign. Of these, 22% had inadequate health
      literacy, 50% had intermediate health literacy, and 28% had adequate health
      literacy skills. Compared to adequate health literacy, limited literacy was
      independently associated with not taking a daily vitamin during pregnancy (OR
      3.6, 95% CI: 1.6, 8.5) and never breastfeeding their infant (OR 1.4, 95% CI: 1.1,
      1.8). The majority (69.4%) of respondents received nine or more text messages a
      day prior to enrollment, one in four participants (24.6%) had changed their
      number within the last six months, and 7.0% of study participants shared a cell
      phone. Controlling for potentially confounding factors, those with limited health
      literacy were more likely to share a cell phone than those with adequate health
      literacy (OR 2.57, 95% CI: 1.79, 3.69). CONCLUSIONS: Text4baby messages should be
      appropriate for low health literacy levels, especially as this population may
      have higher prevalence of targeted unhealthy behaviors. Text4baby and other
      mhealth programs targetting low health literacy populations should also be aware
      of the different ways that these populations use their cell phones, including:
      sharing cell phones, which may mean participants will not receive messages or
      have special privacy concerns; frequently changing cell phone numbers which could
      lead to higher drop-off rates; and the penetrance of text messages in a
      population that receives many messages daily.

PMID- 24872884
TI  - Self-rated literacy level does not explain educational differences in health and
      disease.
AB  - BACKGROUND: Although literacy is increasingly considered to play a role in
      socioeconomic inequalities in health, its contribution to the explanation of
      educational differences in health has remained unexplored. The aim of this study
      was to investigate the contribution of self-rated literacy to educational
      differences in health. METHODS: Data was collected from the Healthy Foundation
      and Lifestyle Segmentation Dataset (n = 4257). Self-rated literacy was estimated
      by individuals' self-reported confidence in reading written English. We used
      logistic regression analyses to assess the association between educational level
      and health (long term conditions and self-rated health). Self-rated literacy and
      other potential explanatory variables were separately added to each model. For
      each added variable we calculated the percentage change in odds ratio to assess
      the contribution to the explanation of educational differences in health.
      RESULTS: People with lower educational attainment level were more likely to
      report a long term condition (OR 2.04, CI 1.80-2.32). These educational
      differences could mostly be explained by age (OR decreased by 27%) and could only
      minimally be explained by self-rated literacy, as measured by self-rated reading
      skills (OR decreased by 1%). Literacy could not explain differences in
      cardiovascular condition or diabetes, and only minimally contributed to mental
      health problems and depression (OR decreased by 5%). The odds of rating ones own
      health more negatively was higher for people with a low educational level
      compared to those with a higher educational level (OR 1.83, CI 1.59-2.010), self
      rated literacy decreased the OR by 7%. CONCLUSION: Measuring self-rated reading
      skills does not contribute significantly to the explanation of educational
      differences in health and disease. Further research should aim for the
      development of objective generic and specific instruments to measure health
      literacy skills in the context of health care, disease prevention and health
      promotion. Such instruments are not only important in the explanation of
      educational differences in health and disease, but can also be used to identify a
      group at risk of poorer health through low basic skills, enabling health services
      and health information to be targeted at those with greater need.

PMID- 24872885
TI  - Human health risk analysis from disinfection by-products (DBPs) in drinking and
      bathing water of some Indian cities.
AB  - BACKGROUND: Human health risk assessment from exposure to disinfection by
      products (DBPs) during drinking and bathing water vary from country to country as
      per life expectancy, body mass index, water consumption pattern and individual
      concentration of DBPs component, etc. METHODS: Present study considered average
      direct water intake per person for adult males and females as 4 & 3 L/day,
      respectively as per Indian literature for risk evaluation from another component
      of pollutant. While other important factor like average life expectancy, body
      weight & body surface area for male and female were considered 64 & 67 years,
      51.9 & 45.4 Kg and 1.54 & 1.38 m(2) respectively as per Indian Council of Medical
      Research and WHO report. The corresponding lifetime cancer risk of the formed
      THMs to human beings was estimated by the USEPA and IRIS method as per Indian
      population. RESULTS: The total cancer risk reached 8.99 E-04 and 8.92 E-04 for
      males and females, respectively, the highest risk from THMs seems to be from the
      inhalation route followed by ingestion and dermal contacts. CONCLUSIONS: The
      multipath way evaluations of lifetime cancer risks for THMs exposure through
      ingestion, dermal absorption, and inhalation exposure were examined at the
      highest degree of danger. Results reveals that water containing THMs of the
      selected water treatment plant of the eastern part of India was unsafe in terms
      of risk evaluation through inhalation and ingestion, while dermal route of risk
      was found very close to permissible limit of USEPA. Sensitivity analysis shows
      that every input parameter is sole responsible for total risk potential, whereas
      exposure duration playing important role for estimation of total risk.

PMID- 24872886
TI  - The effect of shock loading on the performance of a thermophilic anaerobic
      contact reactor at constant organic loading rate.
AB  - The influences of organic loading disturbances on the process performance of a
      thermophilic anaerobic contact reactor treating potato-processing wastewater were
      investigated. For this purpose, while the reactor was operated at steady state
      conditions with organic loading rate of 5.5 kg COD/m(3) . day, an instant acetate
      concentration increase (1 g/L) was introduced to the reactor. During the shock
      loading test of acetate, it was observed that the overall process performance was
      adversely affected by all the shock loading, however, the system reached steady
      state conditions less than 24 hours of operation indicating that thermophilic
      anaerobic contact reactor is resistant to shock loading and be capable of
      returning its normal conditions within a short time period. 

PMID- 24872888
TI  - A new combination formula for treatment of fungal keratitis: an experimental
      study.
AB  - Objective. To formulate and evaluate slow release ketoconazole and ketorolac to
      treat fungal keratitis and associated inflammation. Methods. Experimental study
      with the following outcome measures. Pharmaceutical Evaluation. Mucoadhesive gels
      containing ketoconazole and ketorolac were used. Microbiological in vitro
      evaluation was performed using cup method. In vivo evaluation was performed on 24
      rabbits divided into 2 groups, 12 rabbits each, group A (fast release formula; 6
      times daily) and group B (slow release formula; 3 times daily). Each group was
      divided into two subgroups (6 rabbits each). Both eyes of rabbits were inoculated
      with Candida albicans. The left eye of all rabbits received the combination
      formulae. The right eye for one subgroup received ketoconazole as control 1 while
      the other subgroup received placebo as control 2. Clinical follow-up was done
      and, finally, the corneas were used for microbiological and pathological
      evaluation. Results. Gels containing high polymer concentration showed both high
      viscosity and mucoadhesion properties with slower drug release. The infected eyes
      treated with slow release formula containing both drugs showed better curing of
      the cornea and pathologically less inflammation than eyes treated with fast
      release formula. Conclusion. Slow release formula containing ketoconazole and
      ketorolac showed higher activity than fast release formula against fungal
      keratitis and associated inflammation. 

PMID- 24872887
TI  - Study on the contamination of Abadan public parks soil with Toxocara spp. eggs.
AB  - BACKGROUND: Toxocariasis is one of the most important zoonotic diseases caused by
      Toxocara larva stage in humans. One of the major transmission routes of
      infection, especially in children is pica. The aim of this topic was study the
      contamination of Abadan public parks with Toxocara eggs. MATERIALS AND METHODS:
      Two hundred and ninety one samples of soil were collected from 31 parks. The
      samples were examined for Toxocara spp. eggs by modified floatation method using
      saturated sucrose. The results were analyzed using SPSS version 19 and Chi-square
      test. RESULTS: Eighty five (29.2%) out of 291 samples were infected with Toxocara
      spp. eggs, means19 (61.2%) of the 31 parks were contaminated. There was no
      significant difference between the urban and suburb parks contamination (p =
      0.208) but there was significant relation between contamination with Toxocara
      spp. eggs and traces of cats and dogs presence in the parks (p = 0.001).
      CONCLUSION: As the contamination of Abadan public parks soil with Toxocara spp.
      eggs is relatively high, the people and specially children might get the
      contamination during stay in the parks and measures should be taken to control
      the stray cats and dogs.

PMID- 24872891
TI  - Reaching perinatal women online: the Healthy You, Healthy Baby website and app.
AB  - Overwhelming evidence reveals the close link between unwarranted weight gain
      among childbearing women and childhood adiposity. Yet current barriers limit the
      capacity of perinatal health care providers (PHCPs) to offer healthy lifestyle
      counselling. In response, today's Internet savvy women are turning to online
      resources to access health information, with the potential of revolutionising
      health services by enabling PHCPs to guide women to appropriate online resources.
      This paper presents the findings of a project designed to develop an online
      resource to promote healthy lifestyles during the perinatal period. The
      methodology involved focus groups and interviews with perinatal women and PHCPs
      to determine what online information was needed, in what form, and how best it
      should be presented. The outcome was the development of the Healthy You, Healthy
      Baby website and smartphone app. This clinically-endorsed, interactive online
      resource provides perinatal women with a personalised tool to track their weight,
      diet, physical activity, emotional wellbeing, and sleep patterns based on the
      developmental stage of their child with links to quality-assured information. One
      year since the launch of the online resource, data indicates it provides a low
      cost intervention delivered across most geographic and socioeconomic strata
      without additional demands on health service staff. 

PMID- 24872890
TI  - Sexual orientation disparities in BMI among U.S. adolescents and young adults in
      three race/ethnicity groups.
AB  - Obesity is a key public health issue for US youth. Previous research with
      primarily white samples of youth has indicated that sexual minority females have
      higher body mass index (BMI) and sexual minority males have lower BMI than their
      same-gender heterosexual counterparts, with sexual orientation differences in
      males increasing across adolescence. This research explored whether gender and
      sexual orientation differences in BMI exist in nonwhite racial/ethnic groups.
      Using data from Waves I-IV (1995-2009) of the US National Longitudinal Study of
      Adolescent Health (N = 13,306, ages 11-34 years), we examined associations
      between sexual orientation and BMI (kg/m2) over time, using longitudinal linear
      regression models, stratified by gender and race/ethnicity. Data were analyzed in
      2013. Among males, heterosexual individuals showed greater one-year BMI gains
      than gay males across all race/ethnicity groups. Among females, white and Latina
      bisexual individuals had higher BMI than same-race/ethnicity heterosexual
      individuals regardless of age; there were no sexual orientation differences in
      black/African Americans. Sexual orientation disparities in BMI are a public
      health concern across race/ethnicity groups. Interventions addressing unhealthy
      weight gain in youth must be relevant for all sexual orientations and
      race/ethnicities.

PMID- 24872892
TI  - School-based obesity prevention intervention in Chilean children: effective in
      controlling, but not reducing obesity.
AB  - OBJECTIVE: To evaluate the effectiveness of a 12-month multicomponent obesity
      prevention intervention. Setting. 9 elementary schools in Santiago, Chile.
      Subjects. 6-8 y old low-income children (N = 1474). DESIGN: Randomized controlled
      study; 5 intervention/4 control schools. We trained teachers to deliver nutrition
      contents and improve the quality of PE classes. We determined % healthy snacks
      brought from home, children's nutrition knowledge, nutritional status, duration
      of PE classes, and % time in moderate/vigorous activity (MVA). Effectiveness was
      determined by comparing Delta BMI Z between intervention and control children
      using PROCMIXED. RESULTS: % obesity increased in boys from both types of schools
      and in girls from control schools, while decreasing in girls from intervention
      schools (all nonsignificant). % class time in MVA declined (24.5-16.2) while
      remaining unchanged (24.8-23.7%) in classes conducted by untrained and trained
      teachers, respectively. In boys, BMI Z declined (1.33-1.24) and increased (1.22
      1.35) in intervention and control schools, respectively. In girls, BMI Z remained
      unchanged in intervention schools, while increasing significantly in control
      schools (0.91-1.06, P = 0.024). Interaction group * time was significant for boys
      (P < 0.0001) and girls (P = 0.004). CONCLUSIONS: This intervention was effective
      in controlling obesity, but not preventing it. Even though impact was small,
      results showed that when no intervention is implemented, obesity increases.

PMID- 24872893
TI  - What do healthcare providers advise women with multiple sclerosis regarding
      pregnancy?
AB  - Pregnancy in multiple sclerosis (MS) is considered safe for both the woman and
      the child. Nevertheless, pregnancy issues in MS are complex both from a patient's
      and a provider's perspective. In an anonymous survey, 28 healthcare providers in
      the United States reported on the management of multiple sclerosis (MS) during
      pregnancy. Participants were asked about their recommendations to patients about
      the use of disease modifying therapies during pregnancy and breastfeeding and
      general recommendations about MS and pregnancy. Healthcare providers were also
      asked about sources from which they receive information about the management of
      patients with MS. Results suggested that healthcare providers do not discourage
      pregnancy for women with MS, recommend that women not use disease modifying
      therapies while pregnant, and have a positive view of breastfeeding for women
      with MS. Results also indicated the need for guidelines on patient management for
      pregnant women with MS. 

PMID- 24872896
TI  - Coronary Subclavian Steal Syndrome: An Unusual Cause of Angina in a Post-CABG
      Patient.
AB  - Coronary subclavian steal syndrome is a rare complication of coronary artery
      bypass grafting surgery (CABG) when a left internal mammary artery (LIMA) graft
      is utilized. This syndrome is characterized by retrograde flow from the LIMA to
      the left subclavian artery (SA) when a proximal left SA stenosis is present. We
      describe a unique case of an elderly male who underwent CABG 6 years ago who
      presented with prolonged chest pain, mildly elevated troponins, and unequal
      pulses in his arms. A CTA of the chest demonstrated a severely calcified occluded
      proximal left SA jeopardizing his LIMA graft. Subclavian angiography was
      performed with an attempt to revascularize the patient's occluded left SA which
      was unsuccessful. We referred the patient for nuclear stress testing which
      demonstrated a moderate size area of anterior ischemia on imaging; the patient
      exercised to a fair exercise capacity of 7 METS with no chest pain and no ECG
      changes. Subsequent coronary angiography showed severe native three-vessel
      coronary artery disease with intermittent retrograde blood flow from the LIMA to
      the left SA distal to the occlusion, jeopardizing perfusion to the left anterior
      descending (LAD) coronary artery distribution. He declined further options for
      revascularization and was discharged with medical management. 

PMID- 24872897
TI  - A single step impression technique of flabby ridges using monophase
      polyvinylsiloxane material: a case report.
AB  - Complete denture fabrication in clinically compromised situations such as flabby
      ridges is a challenging task for the clinician. Accurate impressioning of these
      tissues plays a major role in ensuring a well-fitting prosthesis. In this paper,
      the authors have proposed a newer technique of impression making of the flabby
      tissues using a combination of readily available newer and older materials to
      ensure an accurate and easy impression of these tissues. 

PMID- 24872894
TI  - Carbon nanotubes: an emerging drug carrier for targeting cancer cells.
AB  - During recent years carbon nanotubes (CNTs) have been attracted by many
      researchers as a drug delivery carrier. CNTs are the third allotropic form of
      carbon-fullerenes which were rolled into cylindrical tubes. To be integrated into
      the biological systems, CNTs can be chemically modified or functionalised with
      therapeutically active molecules by forming stable covalent bonds or
      supramolecular assemblies based on noncovalent interactions. Owing to their high
      carrying capacity, biocompatibility, and specificity to cells, various cancer
      cells have been explored with CNTs for evaluation of pharmacokinetic parameters,
      cell viability, cytotoxicty, and drug delivery in tumor cells. This review
      attempts to highlight all aspects of CNTs which render them as an effective
      anticancer drug carrier and imaging agent. Also the potential application of CNT
      in targeting metastatic cancer cells by entrapping biomolecules and anticancer
      drugs has been covered in this review. 

PMID- 24872895
TI  - Abnormal baseline brain activity in patients with pulsatile tinnitus: a resting
      state FMRI study.
AB  - Numerous investigations studying the brain functional activity of the tinnitus
      patients have indicated that neurological changes are important findings of this
      kind of disease. However, the pulsatile tinnitus (PT) patients were excluded in
      previous studies because of the totally different mechanisms of the two subtype
      tinnitus. The aim of this study is to investigate whether altered baseline brain
      activity presents in patients with PT using resting-state functional magnetic
      resonance imaging (rs-fMRI) technique. The present study used unilateral PT
      patients (n = 42) and age-, sex-, and education-matched normal control subjects
      (n = 42) to investigate the changes in structural and amplitude of low-frequency
      (ALFF) of the brain. Also, we analyzed the relationships between these changes
      with clinical data of the PT patients. Compared with normal controls, PT patients
      did not show any structural changes. PT patients showed significant increased
      ALFF in the bilateral precuneus, and bilateral inferior frontal gyrus (IFG) and
      decreased ALFF in multiple occipital areas. Moreover, the increased THI score and
      PT duration was correlated with increased ALFF in precuneus and bilateral IFG.
      The abnormalities of spontaneous brain activity reflected by ALFF measurements in
      the absence of structural changes may provide insights into the neural
      reorganization in PT patients. 

PMID- 24872898
TI  - Oral Myiasis Caused by Chrysomya bezziana in Anterior Maxilla.
AB  - Oral myiasis is a rare pathology and is associated with poor oral hygiene,
      alcoholism, senility, suppurating lesions, and severe halitosis. It arises from
      invasion of body tissues or cavities of living animals by maggots or larvae of
      certain dipterian flies. It is mostly reported in developing countries and in the
      tropics. We hereby report a rare case of oral myiasis in a 70-year-old female
      with extensive necrotic oral lesion burrowing into the hard palate through which
      numerous live maggots (larvae) and seen emerging out and discuss the definition,
      etiology, predisposing factors, classification, and management of the same.
      Furthermore, the life cycle of the causative organism in the present case, that
      is, Chrysomya bezziana, has also been discussed. 

PMID- 24872899
TI  - Severe Pulmonary Suppuration with Infection-Induced Systemic Inflammatory
      Response Syndrome following Tongue Cancer Surgery in a Patient Undergoing
      Tocilizumab Therapy for Rheumatoid Arthritis.
AB  - A 65-year-old woman with rheumatoid arthritis treated by tocilizumab (TCZ)
      presented with tongue squamous cell carcinoma. While surgery was performed
      without any complications the aspiration pneumonia rapidly worsened by
      postoperative day 2 and severe pulmonary suppuration in the right lung field with
      infection-induced systemic inflammatory response syndrome (SIRS) was diagnosed.
      Antibiotic and respirator treatment improved her condition. The anti-inflammatory
      effect of TCZ may mask the symptoms and signs of severe infection with SIRS. 

PMID- 24872900
TI  - Aesthetic rehabilitation of a complicated crown-root fracture of the maxillary
      incisor: combination of orthodontic and implant treatment.
AB  - The aim of this paper is to present a complex rehabilitation, of fractured tooth,
      with implants in anterior region considering the orthodontics extrusion to
      clinical success. At 7 years old, the patient fractured the maxillary left
      central incisor and the dentist did a crown with the fragment. Twenty years
      later, the patient was referred to a dental clinic for orthodontic treatment,
      with the chief complaint related to an accentuated deep bite, and a professional
      started an orthodontic treatment. After sixteen months of orthodontic treatment,
      tooth 21 fractured. The treatment plan included an orthodontic extrusion of tooth
      21 and implant placement. This case has been followed up and the clinical and
      radiographic examinations show excellence esthetic results and satisfaction of
      patient. The forced extrusion can be a viable treatment option in the management
      of crown root fracture of an anterior tooth to gain bone in a vertical direction.
      This case emphasizes that to achieve the esthetic result a multidisciplinary
      approach is necessary. 

PMID- 24872901
TI  - A Gut Gone to Pot: A Case of Cannabinoid Hyperemesis Syndrome due to K2, a
      Synthetic Cannabinoid.
AB  - Cannabinoid Hyperemesis Syndrome (CHS) was first described in 2004. Due to its
      novelty, CHS is often unrecognized by clinicians leading to expensive workup of
      these patients with cyclical symptoms. It may take up to 9 years to diagnose CHS.
      CHS is characterized by cyclical nausea and vomiting, abdominal pain, and an
      unusual compulsion to take hot showers in the presence of chronic use of
      cannabinoids. Cannabicyclohexanol is a synthetic cannabinoid, popularly known as
      K2 spice. It is a popular marijuana alternative among teenagers and young adults
      since it is readily available as herbal incense. Unlike marijuana, many users
      know that K2 is not detected in conventional urine drug screens, allowing those
      users to conceal their intake from typical detection methods. Serum or urine gas
      chromatography mass spectrophotometry is diagnostic, though not widely available.
      Thus, it is imperative for clinicians to recognize CHS, even with negative UDS,
      to provide cost-effective care. We present a 38-year-old man with a 10-year
      history of cannabis, and 1-year history of K2 abuse admitted with 1-week history
      of episodes of nausea, vomiting of clear fluids, and epigastric discomfort.
      Symptoms are relieved only by hot showers. Extensive laboratory, radiologic, and
      endoscopic evaluation was unrevealing. CHS was diagnosed, based on proposed
      criteria by Simonetti et al. 

PMID- 24872902
TI  - A novel use of early radiation therapy in the treatment of hyperbilirubinemia in
      a patient with primary hepatic lymphoma and chronic hepatitis C.
AB  - Lymphomas arising in the liver are extremely rare. Here, we describe a case of
      Hepatitis C virus infection with primary hepatic lymphoma (PHL) presenting with
      hyperbilirubinemia. A 45-year-old African American male presented with abdominal
      pain, pruritus, and itching for two days. CT of abdomen and pelvis with contrast
      showed numerous masses in the liver. The liver biopsy was consistent with diffuse
      large B cell lymphoma (DLBCL). Conventional chemotherapy was avoided initially
      because of hyperbilirubinemia. Hence, radiation therapy was given initially to
      reduce his bilirubin levels and tumor size. The patient was able to complete six
      cycles of rituximab combined with cyclophosphamide, adriamycin, vincristine, and
      prednisone (R-CHOP) chemotherapy and achieved a complete response verified by
      positron emission tomography-computed tomography (PET-CT). PHL should be
      considered when there are numerous space occupying liver lesions seen on imaging.
      Hyperbilirubinemia may be a reason for delay in treatment for some of these
      patients. Hence, the role of radiation therapy prior to treatment with R-CHOP is
      an alternative to management for stage IV diffuse large B cell lymphoma. 

PMID- 24872903
TI  - Substance Use and Associated Factors among University Students in Ethiopia: A
      Cross-Sectional Study.
AB  - Studies indicate that substance use among Ethiopian adolescents is considerably
      rising; in particular college and university students are the most at risk of
      substance use. The aim of the study was to assess substance use and associated
      factors among university students. A cross-sectional survey was carried out among
      1040 Haramaya University students using self-administered structured
      questionnaire. Multistage sampling technique was used to select students.
      Descriptive statistics, bivariate, and multivariate analysis were done. About two
      thirds (62.4%) of the participants used at least one substance. The most commonly
      used substance was alcohol (50.2%). Being male had strong association with
      substance use (AOR (95% CI), 3.11 (2.20, 4.40)). The odds of substance use
      behaviour is higher among third year students (AOR (95% CI), 1.48 (1.01, 2.16)).
      Being a follower of Muslim (AOR (95% CI), 0.62 (0.44, 0.87)) and Protestant (AOR
      (95% CI), 0.25 (0.17, 0.36)) religions was shown to be protective of substance
      use. Married (AOR (95% CI), 1.92 (1.12, 3.30)) and depressed (AOR (95% CI), 3.30
      (2.31, 4.72)) students were more likely to use substances than others. The
      magnitude of substance use was high. This demands special attention, emergency
      preventive measures, and targeted information, education and communication
      activity. 

PMID- 24872904
TI  - Electrochemical Immunoassay of Escherichia coli O157:H7 Using Ag@SiO2
      Nanoparticles as Labels.
AB  - Silica coated silver (Ag@SiO2) nanoparticles were prepared and characterized by
      transmission electron microscope (TEM) and UV-vis absorption, and the
      nanoparticles were used as labels in sandwich-type immunosensor of Escherichia
      coli O157:H7 (E. coli O157:H7). The labels involved in immunoreaction were
      dissolved by mixed acid of hydrofluoric acid and nitric acid, and the released
      Ag(+) ions were electrochemical stripping analyzed (via differential pulse
      voltammetry, DPV) at poly(acrylic acid)/poly(diallyldimethylammonium
      chloride)/carbon nanotubes (PAA/PDCNT) modified glass carbon electrode (GCE),
      which obviously enhanced the signal of Ag(+) stripping. Then, the number of E.
      coli O157:H7 could be indirectly reflected by the signal intensity of labeled
      Ag(+). And the results showed that the DPV signals were proportional to the
      logarithm of the E. coli O157:H7 concentration in the range from 20 cfu/mL to 8.0
      * 10(3) cfu/mL with the detection limit of 13 cfu/mL. 

PMID- 24872905
TI  - Recent movement on education and training in health informatics.

PMID- 24872906
TI  - Massive open online course for health informatics education.
AB  - OBJECTIVES: This paper outlines a new method of teaching health informatics to
      large numbers of students from around the world through a Massive Open Online
      Course (MOOC). METHODS: The Health Informatics Forum is a social networking site
      for educating health informatics students and professionals [corrected]. It is
      running a MOOC for students from around the world that uses creative commons
      licenced content funded by the US government and developed by five US
      universities. The content is delivered through narrated lectures with slides that
      can be viewed online with discussion threads on the forum for class interactions.
      Students can maintain a professional profile, upload photos and files, write
      their own blog posts and post discussion threads on the forum. RESULTS: The
      Health Informatics Forum MOOC has been accessed by 11,316 unique users from 127
      countries from August 2, 2012 to January 24, 2014. Most users accessed the MOOC
      via a desktop computer, followed by tablets and mobile devices and 55% of users
      were female. Over 400,000 unique users have now accessed the wider Health
      Informatics Forum since it was established in 2008. CONCLUSIONS: Advances in
      health informatics and educational technology have both created a demand for
      online learning material in health informatics and a solution for providing it.
      By using a MOOC delivered through a social networking platform it is hoped that
      high quality health informatics education will be able to be delivered to a large
      global audience of future health informaticians without cost.

PMID- 24872907
TI  - Development of health information search engine based on metadata and ontology.
AB  - OBJECTIVES: The aim of the study was to develop a metadata and ontology-based
      health information search engine ensuring semantic interoperability to collect
      and provide health information using different application programs. METHODS:
      Health information metadata ontology was developed using a distributed semantic
      Web content publishing model based on vocabularies used to index the contents
      generated by the information producers as well as those used to search the
      contents by the users. Vocabulary for health information ontology was mapped to
      the Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT), and a list
      of about 1,500 terms was proposed. The metadata schema used in this study was
      developed by adding an element describing the target audience to the Dublin Core
      Metadata Element Set. RESULTS: A metadata schema and an ontology ensuring
      interoperability of health information available on the internet were developed.
      The metadata and ontology-based health information search engine developed in
      this study produced a better search result compared to existing search engines.
      CONCLUSIONS: Health information search engine based on metadata and ontology will
      provide reliable health information to both information producer and information
      consumers.

PMID- 24872908
TI  - Impact of doctors' resistance on success of drug utilization review system.
AB  - OBJECTIVES: The drug utilization review (DUR) system, which checks any conflict
      event of medications, contributes to improve patient safety. One of the important
      barriers in its adoption is doctors' resistance. This study aimed to analyze the
      impacts of doctors' resistance on the success of the DUR system. METHODS: This
      study adopted an augmented the DeLone and McLean Information System (D&M IS)
      Success Model (2003), which used doctors' resistance as a socio-technological
      measure. This study framework is the same as that of the D&M IS Success Model in
      that it is based on qualities, such as system, information, and services. The
      major difference is that this study excluded the variable 'use' because it was
      not statistically significant for mandatory systems. A survey of doctors who used
      computers to enter prescriptions was conducted at a Korean tertiary hospital in
      February 2012. RESULTS: This study is very meaningful in that it is the first
      study to explore the success factors of the DUR system associated with doctors'
      resistance. Doctors' resistance to the DUR system was not statistically
      associated with user usefulness, whereas it affected user satisfaction.
      CONCLUSIONS: The results indicate that doctors still complain of discomfort in
      using the DUR system in the outpatient clinical setting, even though they admit
      that it contributes to patient safety. To mitigate doctors' resistance and raise
      user satisfaction, more opinions from doctors regarding the DUR system have to be
      considered and have to be reflected in the system.

PMID- 24872909
TI  - Characteristics desired in clinical data warehouse for biomedical research.
AB  - OBJECTIVES: Due to the unique characteristics of clinical data, clinical data
      warehouses (CDWs) have not been successful so far. Specifically, the use of CDWs
      for biomedical research has been relatively unsuccessful thus far. The
      characteristics necessary for the successful implementation and operation of a
      CDW for biomedical research have not clearly defined yet. METHODS: THREE EXAMPLES
      OF CDWS WERE REVIEWED: a multipurpose CDW in a hospital, a CDW for independent
      multi-institutional research, and a CDW for research use in an institution. After
      reviewing the three CDW examples, we propose some key characteristics needed in a
      CDW for biomedical research. RESULTS: A CDW for research should include an honest
      broker system and an Institutional Review Board approval interface to comply with
      governmental regulations. It should also include a simple query interface, an
      anonymized data review tool, and a data extraction tool. Also, it should be a
      biomedical research platform for data repository use as well as data analysis.
      CONCLUSIONS: The proposed characteristics desired in a CDW may have limited
      transfer value to organizations in other countries. However, these analysis
      results are still valid in Korea, and we have developed clinical research data
      warehouse based on these desiderata.

PMID- 24872910
TI  - Development of smartphone educational application for patients with coronary
      artery disease.
AB  - OBJECTIVES: This study was conducted to develop a smartphone application (app) as
      an educational learning instrument for coronary artery disease (CAD) patients and
      to assess the users' level of satisfaction. METHODS: This methodological research
      involves elicited learning content for CAD patients to develop a learning
      instrument using the smartphone app. The app was developed according to the steps
      of Assessment, Design, Development, Implementation, and Evaluation, which is a
      systematic instructional design model. The levels of satisfaction with the
      developed smartphone app among 30 outpatients with CAD were assessed via a
      questionnaire during their visits to a cardiology outpatient department. RESULTS:
      A smartphone app 'Strong Heart' was developed through reviewing the literature
      associated with education for CAD patients under professional supervision and
      searching for medical smartphone apps that are already available. The learning
      contents include six main sections containing essential learning issues in
      managing CAD and additional information to attract the user's attention, such as
      patient cases and quizzes. After modification with feedback from experts, the app
      was finally developed and evaluated by patients who reported that they were
      satisfied with the usefulness of the app. CONCLUSIONS: The developed smartphone
      app is available on both the iPhone App Store and the Android Play Store.
      Patients with CAD may utilize the app for supporting educational material without
      limitations of time and space.

PMID- 24872911
TI  - Prediction Model for Health-Related Quality of Life of Elderly with Chronic
      Diseases using Machine Learning Techniques.
AB  - OBJECTIVES: The purposes of this study were to identify the factors that affect
      the health-related quality of life (HRQoL) of the elderly with chronic diseases
      and to subsequently develop from such factors a prediction model to help identify
      HRQoL risk groups that require intervention. METHODS: We analyzed a set of
      secondary data regarding 716 individuals extracted from the Korea National Health
      and Nutrition Examination Survey from 2008 to 2010. The statistical package of
      SPSS and MATLAB were used for data analysis and development of the prediction
      model. The algorithms used in the study were the following: stepwise logistic
      regression (SLR) analysis and machine learning (ML) techniques, such as decision
      tree, random forest, and support vector machine methods. RESULTS: FIVE FACTORS
      WITH STATISTICAL SIGNIFICANCE WERE IDENTIFIED FOR HRQOL IN THE ELDERLY WITH
      CHRONIC DISEASES: 'monthly income', 'diagnosis of chronic disease', 'depression',
      'discomfort', and 'perceived health status.' The SLR analysis showed the best
      performance with accuracy = 0.93 and F-score = 0.49. The results of this study
      provide essential materials that will help formulate personalized health
      management strategies and develop interventions programs towards the improvement
      of the HRQoL for elderly people with chronic diseases. CONCLUSIONS: Our study is,
      to our best knowledge, the first attempt to identify the influencing factors and
      to apply prediction models for the HRQoL of the elderly with chronic diseases by
      using ML techniques as an alternative and complement to the traditional
      statistical approaches.

PMID- 24872912
TI  - Impacts of hospitals' innovativeness on information system outsourcing decisions.
AB  - OBJECTIVES: The purpose of this study was to identify the effects of hospitals'
      innovativeness on outsourcing decision-making regarding four information system
      (IS) functions, namely, software programs, network maintenance, hardware systems,
      and PC/printer maintenance. METHODS: Using the 2011 roster of the Korean Hospital
      Association, this study selected 311 general hospitals as a study population.
      After identifying the managers who were in charge of outsourcing, this study
      administered questionnaires. A total of 103 hospitals responded. RESULTS: Of the
      responding hospitals, 55.34% outsourced at least one IS function, whereas 88.35%
      outsourced at least one managerial function. IS outsourcing was motivated by the
      need for outside experts, but other managerial functions were outsourced for cost
      savings. Innovative and early adopter hospitals were 4.52 and 4.91 times more
      likely to outsource IS functions related with work processes (i.e., software and
      network maintenance) than early and late majority hospitals, respectively. IT
      outsourcing effectiveness significantly influenced the outsourcing decisions
      regarding four IS functions. Hospitals that had perceived more risks of
      outsourcing significantly preferred non-outsourcing on their hardware systems,
      but the risks of outsourcing were not significant for outsourcing decisions
      regarding the other IS functions. Hospitals' innovativeness also significantly
      explained the quantity of innovation adoptions. Innovative and early adopter
      hospitals did more outsourcing than early and late majority hospitals.
      CONCLUSIONS: Hospitals' innovativeness influences decision-making regarding
      outsourcing. Innovative hospitals are more likely to outsource their work-process
      related IS functions. Thus, organizational traits, especially hospitals'
      innovativeness, should be considered as a key success factor for IS management.

PMID- 24872913
TI  - DialysisNet: Application for Integrating and Management Data Sources of
      Hemodialysis Information by Continuity of Care Record.
AB  - OBJECTIVES: Health Avatar Beans was for the management of chronic kidney disease
      and end-stage renal disease (ESRD). This article is about the DialysisNet system
      in Health Avatar Beans for the seamless management of ESRD based on the personal
      health record. METHODS: For hemodialysis data modeling, we identified common data
      elements for hemodialysis information (CDEHI). We used ASTM continuity of care
      record (CCR) and ISO/IEC 11179 for the compliance method with a standard model
      for the CDEHI. According to the contents of the ASTM CCR, we mapped the CDHEI to
      the contents and created the metadata from that. It was transformed and parsed
      into the database and verified according to the ASTM CCR/XML schema definition
      (XSD). DialysisNet was created as an iPad application. The contents of the CDEHI
      were categorized for effective management. For the evaluation of information
      transfer, we used CarePlatform, which was developed for data access. The metadata
      of CDEHI in DialysisNet was exchanged by the CarePlatform with semantic
      interoperability. RESULTS: The CDEHI was separated into a content list for
      individual patient data, a contents list for hemodialysis center data,
      consultation and transfer form, and clinical decision support data. After
      matching to the CCR, the CDEHI was transformed to metadata, and it was
      transformed to XML and proven according to the ASTM CCR/XSD. DialysisNet has
      specific consideration of visualization, graphics, images, statistics, and
      database. CONCLUSIONS: We created the DialysisNet application, which can
      integrate and manage data sources for hemodialysis information based on CCR
      standards.

PMID- 24872914
TI  - Development and validation of web-based nomograms to predict postoperative
      invasive component in ductal carcinoma in situ at needle breast biopsy.
AB  - OBJECTIVES: Although sonography-guided core needle biopsy is a highly targeted
      method, there is a possibility of an invasive component after surgical excision
      of ductal carcinoma in situ (DCIS) of the breast. This study was performed to
      develop and validate nomograms to predict the postoperative invasive component in
      DCIS at core needle biopsy. METHODS: Two nomograms were developed using the data
      of previous meta-analysis and multivariate analysis. Nomograms were validated
      externally using the data of the authors' affiliation. The accuracy was validated
      by the expected-to-observed ratio and the Hosmer-Lemeshow goodness-of-fit test.
      Discrimination was validated by the area under the curve (AUC) of receiver
      operating characteristic (ROC) curve analysis. RESULTS: The nomogram using the
      meta-analysis study data was developed at http://dcis-m.surgery.kr.pe/, and the
      nomogram using the multivariate analysis study data was developed at http://dcis
      k.surgery.kr.pe/. The Hosmer-Lemeshow goodness-of-fit test showed that the
      nomogram using multivariate analysis data (p = 0.131) was better calibrated than
      that using meta-analysis data (p < 0.001). ROC curve analysis showed
      statistically significant power of discrimination in both nomograms (AUC = 0.776,
      0.751). CONCLUSIONS: Both nomograms showed statistically significant
      discriminatory power, but the nomogram using the data of multivariate analysis
      was simpler and more reliable. These would be useful for the prediction of
      invasive cancer and the need for sentinel node biopsy in DCIS at core needle
      biopsy.

PMID- 24872916
TI  - A case of spontaneous cerebrospinal fluid rhinorrhea: Accurate detection of the
      leak point by magnetic resonance cisternography.
AB  - BACKGROUND: Spontaneous cerebrospinal fluid (CSF) rhinorrhea is a rare entity.
      The accurate preoperative localization of the leak point is essential for
      planning surgical treatment, but is sometimes difficult. To localize the leak
      point, magnetic resonance cisternography (MRC) is the method of choice, but its
      effectiveness remains unclear. CASE DESCRIPTION: A 34-year-old mildly obese
      female experienced spontaneous CSF rhinorrhea after an attack of bronchial
      asthma. High-resolution computed tomography (CT) failed to reveal the leak point,
      while MRC demonstrated an arachnoid herniation at the olfactory cleft. The
      patient underwent endoscopic endonasal repair of the CSF leak with success. There
      has been no recurrence of CSF rhinorrhea for 14 months after surgery followed by
      the administration of acetazolamide. CONCLUSION: We report a rare case of
      spontaneous CSF rhinorrhea associated with benign intracranial hypertension, in
      which the leak point was successfully detected by MRC. The CSF leak was
      completely repaired by minimally invasive endoscopic endonasal surgery. MRC may
      be a reliable method for detecting CSF leak points.

PMID- 24872917
TI  - Full-endoscopic interlaminar removal of chronic lumbar epidural hematoma after
      spinal manipulation.
AB  - BACKGROUND: Spinal manipulation is widely used for low back pain treatments.
      Complications associated with spinal manipulation are seen. Lumbar epidural
      hematoma (EDH) is one of the complications reported in the literature. If lumbar
      chronic EDH symptoms are present, which are similar to those of a herniated
      nucleus pulposus, surgery may be considered if medical treatment fails.
      Percutaneous endoscopic discectomy utilizing an interlaminar approach can be
      successfully applied to those with herniated nucleus pulposus. We use the same
      technique to remove the lumbar chronic EDH, which is the first documented report
      in the related literature. METHODS: We present a case with chronic lumbar EDH
      associated with spinal manipulation. Neurologic deficits were noted on physical
      examination. We arranged for a full-endoscopic interlaminar approach to remove
      the hematoma for the patient with the rigid endoscopy (Vertebris system; Richard
      Wolf, Knittlingen, Germany). RESULTS: After surgery, the patient's radiculopathy
      immediately began to disappear. Magnetic resonance imaging (MRI) follow-up 10
      days after the surgery revealed no residual hematoma. No complications were noted
      during the outpatient department follow up. CONCLUSIONS: Lumbar EDH is a possible
      complication of spinal manipulation. Patient experiencing rapidly progressive
      neurologic deficit require early surgical evacuation, while conservative
      treatment may only be applied to those with mild symptoms. A percutaneous full
      endoscopic interlaminar approach may be a viable alternative for the treatment of
      those with chronic EDH with progressive neurologic deficits.

PMID- 24872918
TI  - Modified method for microvascular anastomosis suturing.
AB  - BACKGROUND: Suturing of microvascular anastomosis is still a time-consuming
      procedure, despite the fact that different techniques and devices were designed
      to reduce the operation time and increase the patency rate. This paper reports a
      method for microvascular anastomosis suturing, using foam rubber cylindrical
      mandrel, which helps to solve the above-stated problems. METHODS: The principle
      of method is based on running suture, imposed around the foam rubber mandrel.
      Then the suture is divided into separate stitches. After the visual control of
      anastomosis lumen knots are tightened. The procedure is the same for front and
      back parts of anastomosis. RESULTS: Testing of technique in the laboratory showed
      the possibility of using a single thread per anastomosis and reducing the time
      for suturing from 17.3 to 15.4 min compared with standard procedure. CONCLUSIONS:
      Described technique allows surgeon to control the lumen of anastomosis before
      tightening knots, reduces time of work, and does not increase the cost of
      operation.

PMID- 24872919
TI  - Expanding contralateral epidural hematoma causing acute intraoperative brain
      swelling.

PMID- 24872920
TI  - Sudden unexpected nocturnal death in Chiari type 1 malformation and potential
      role of opioid analgesics.

PMID- 24872921
TI  - Cerebellar hemorrhage after embolization of ruptured vertebral dissecting
      aneurysm proximal to PICA including parent artery.
AB  - BACKGROUND: Some complications related to vertebral artery occlusion by
      endovascular technique have been reported. However, cerebellar hemorrhage after
      vertebral artery occlusion in subacute phase is rare. In this report, we describe
      a patient who showed cerebellar hemorrhage during hypertensive therapy for
      vasospasm after embolization of a vertebral dissecting aneurysm. CASE
      DESCRIPTION: A 56-year-old female with a ruptured vertebral dissecting aneurysm
      proximal to the posterior inferior cerebellar artery developed cerebellar
      hemorrhage 15 days after embolization of the vertebral artery, including the
      dissected site. In this patient, the preserved posterior inferior cerebellar
      artery fed by retrograde blood flow might have been hemodynamically stressed
      during hypertensive and antiplatelet therapies for subarachnoid hemorrhage,
      resulting in cerebellar hemorrhage. CONCLUSION: Although cerebellar hemorrhage is
      not prone to occur in the nonacute stage of embolization of the vertebral artery,
      it should be taken into consideration that cerebellar hemorrhage may occur during
      hypertensive treatment.

PMID- 24872923
TI  - A new total wrist fusion locking plate for patients with small hands or with
      failed partial wrist fusion: preliminary experience.
AB  - The author has designed a custom-made titanium plate for total wrist fusion for
      small-handed persons or patients with failed partial wrist fusions. From May 2011
      to April 2013, this plate was used on 13 wrists, 5 of them with a minimum follow
      up of 1 year. This implant is downsized compared with the standard wrist fusion
      plate: lower in profile, shorter in length, and narrower than the standard one.
      It is fixed to the radius by means of 2.7-mm screws and to the capitate and third
      metacarpal with 2.4-mm screws. In the curved plate all the screws are locked to
      the plate with a predetermined coaxial angle. The plate has a curvature to fit
      the dorsum of the carpus; it is 10 degrees  dorsally extended and has undercuts
      on the contact areas at the radius and third metacarpal dorsal surface. The
      indication for this implant is a short-statured patient for whom the standard
      plate is too large and bulky; a failed partial wrist fusion or proximal row
      carpectomy, for which a shorter plate is needed because only one articulation
      should be fused (midcarpal or radiocapitate joint); or both. The five wrists (two
      primary fusions and three failed radioscapholunate [RSL] fusions) healed between
      11 and 14 weeks. No plate loosening was observed, and none of the patients felt
      painful prominence to the distal end of the plate on the dorsum of the hand. 

PMID- 24872924
TI  - Identification of Criticality in Neuronal Avalanches: II. A Theoretical and
      Empirical Investigation of the Driven Case.
AB  - The observation of apparent power laws in neuronal systems has led to the
      suggestion that the brain is at, or close to, a critical state and may be a self
      organised critical system. Within the framework of self-organised criticality a
      separation of timescales is thought to be crucial for the observation of power
      law dynamics and computational models are often constructed with this property.
      However, this is not necessarily a characteristic of physiological neural
      networks-external input does not only occur when the network is at rest/a steady
      state. In this paper we study a simple neuronal network model driven by a
      continuous external input (i.e. the model does not have an explicit separation of
      timescales from seeding the system only when in the quiescent state) and
      analytically tuned to operate in the region of a critical state (it reaches the
      critical regime exactly in the absence of input-the case studied in the companion
      paper to this article). The system displays avalanche dynamics in the form of
      cascades of neuronal firing separated by periods of silence. We observe partial
      scale-free behaviour in the distribution of avalanche size for low levels of
      external input. We analytically derive the distributions of waiting times and
      investigate their temporal behaviour in relation to different levels of external
      input, showing that the system's dynamics can exhibit partial long-range temporal
      correlations. We further show that as the system approaches the critical state by
      two alternative 'routes', different markers of criticality (partial scale-free
      behaviour and long-range temporal correlations) are displayed. This suggests that
      signatures of criticality exhibited by a particular system in close proximity to
      a critical state are dependent on the region in parameter space at which the
      system (currently) resides. 

PMID- 24872925
TI  - Frequency Preference Response to Oscillatory Inputs in Two-dimensional Neural
      Models: A Geometric Approach to Subthreshold Amplitude and Phase Resonance.
AB  - We investigate the dynamic mechanisms of generation of subthreshold and phase
      resonance in two-dimensional linear and linearized biophysical (conductance
      based) models, and we extend our analysis to account for the effect of simple,
      but not necessarily weak, types of nonlinearities. Subthreshold resonance refers
      to the ability of neurons to exhibit a peak in their voltage amplitude response
      to oscillatory input currents at a preferred non-zero (resonant) frequency. Phase
      resonance refers to the ability of neurons to exhibit a zero-phase (or zero-phase
      shift) response to oscillatory input currents at a non-zero (phase-resonant)
      frequency. We adapt the classical phase-plane analysis approach to account for
      the dynamic effects of oscillatory inputs and develop a tool, the envelope-plane
      diagrams, that captures the role that conductances and time scales play in
      amplifying the voltage response at the resonant frequency band as compared to
      smaller and larger frequencies. We use envelope-plane diagrams in our analysis.
      We explain why the resonance phenomena do not necessarily arise from the presence
      of imaginary eigenvalues at rest, but rather they emerge from the interplay of
      the intrinsic and input time scales. We further explain why an increase in the
      time-scale separation causes an amplification of the voltage response in addition
      to shifting the resonant and phase-resonant frequencies. This is of fundamental
      importance for neural models since neurons typically exhibit a strong separation
      of time scales. We extend this approach to explain the effects of nonlinearities
      on both resonance and phase-resonance. We demonstrate that nonlinearities in the
      voltage equation cause amplifications of the voltage response and shifts in the
      resonant and phase-resonant frequencies that are not predicted by the
      corresponding linearized model. The differences between the nonlinear response
      and the linear prediction increase with increasing levels of the time scale
      separation between the voltage and the gating variable, and they almost disappear
      when both equations evolve at comparable rates. In contrast, voltage responses
      are almost insensitive to nonlinearities located in the gating variable equation.
      The method we develop provides a framework for the investigation of the preferred
      frequency responses in three-dimensional and nonlinear neuronal models as well as
      simple models of coupled neurons. 

PMID- 24872926
TI  - Network symmetry and binocular rivalry experiments.
AB  - Hugh Wilson has proposed a class of models that treat higher-level decision
      making as a competition between patterns coded as levels of a set of attributes
      in an appropriately defined network (Cortical Mechanisms of Vision, pp. 399-417,
      2009; The Constitution of Visual Consciousness: Lessons from Binocular Rivalry,
      pp. 281-304, 2013). In this paper, we propose that symmetry-breaking Hopf
      bifurcation from fusion states in suitably modified Wilson networks, which we
      call rivalry networks, can be used in an algorithmic way to explain the
      surprising percepts that have been observed in a number of binocular rivalry
      experiments. These rivalry networks modify and extend Wilson networks by
      permitting different kinds of attributes and different types of coupling. We
      apply this algorithm to psychophysics experiments discussed by Kovacs et al.
      (Proc. Natl. Acad. Sci. USA 93:15508-15511, 1996), Shevell and Hong (Vis.
      Neurosci. 23:561-566, 2006; Vis. Neurosci. 25:355-360, 2008), and Suzuki and
      Grabowecky (Neuron 36:143-157, 2002). We also analyze an experiment with four
      colored dots (a simplified version of a 24-dot experiment performed by Kovacs),
      and a three-dot analog of the four-dot experiment. Our algorithm predicts
      surprising differences between the three- and four-dot experiments. 

PMID- 24872922
TI  - Neurosurgical confocal endomicroscopy: A review of contrast agents, confocal
      systems, and future imaging modalities.
AB  - BACKGROUND: The clinical application of fluorescent contrast agents (fluorescein,
      indocyanine green, and aminolevulinic acid) with intraoperative microscopy has
      led to advances in intraoperative brain tumor imaging. Their properties,
      mechanism of action, history of use, and safety are analyzed in this report along
      with a review of current laser scanning confocal endomicroscopy systems.
      Additional imaging modalities with potential neurosurgical utility are also
      analyzed. METHODS: A COMPREHENSIVE LITERATURE SEARCH WAS PERFORMED UTILIZING
      PUBMED AND KEY WORDS: In vivo confocal microscopy, confocal endomicroscopy,
      fluorescence imaging, in vivo diagnostics/neoplasm, in vivo molecular imaging,
      and optical imaging. Articles were reviewed that discussed clinically available
      fluorophores in neurosurgery, confocal endomicroscopy instrumentation, confocal
      microscopy systems, and intraoperative cancer diagnostics. RESULTS: Current
      clinically available fluorescent contrast agents have specific properties that
      provide microscopic delineation of tumors when imaged with laser scanning
      confocal endomicroscopes. Other imaging modalities such as coherent anti-Stokes
      Raman scattering (CARS) microscopy, confocal reflectance microscopy, fluorescent
      lifetime imaging (FLIM), two-photon microscopy, and second harmonic generation
      may also have potential in neurosurgical applications. CONCLUSION: In addition to
      guiding tumor resection, intraoperative fluorescence and microscopy have the
      potential to facilitate tumor identification and complement frozen section
      analysis during surgery by providing real-time histological assessment. Further
      research, including clinical trials, is necessary to test the efficacy of
      fluorescent contrast agents and optical imaging instrumentation in order to
      establish their role in neurosurgery.

PMID- 24872927
TI  - Why is Research on Herbal Medicinal Products Important and How Can We Improve Its
      Quality?
AB  - Research on herbal medicinal products is increasingly published in "Western"
      scientific journals dedicated primarily to conventional medicines. Publications
      are concerned mainly not only on the issues of safety and interactions, but also
      on efficacy. In reviews, a recurring complaint has been a lack of quality
      studies. In this opinion article, we present the case of Chinese herbal medicines
      as an example, as they have been extensively used in the global market and
      increasingly studied worldwide. We analyze the potential reasons for problems and
      propose some ways forward. As in the case of any drug, clinical trials for
      safety, efficacy, and/or effectiveness are the ultimate demonstration of
      therapeutic usefulness of herbal products. These will only make scientific sense
      when the tested herbal products are authentic, standardized, and quality
      controlled, if good practice guidelines of evidence-based medicine are followed,
      and if relevant controls and outcome measures are scientifically defined. Herbal
      products are complex mixtures, and for such complexity, an obvious approach for
      mechanistic studies is network pharmacology based on omic tools and approaches,
      which has already begun to revolutionize the study of conventional drugs,
      emphasizing networks, interactions, and polypharmacological features behind the
      action of many drugs. 

PMID- 24872928
TI  - Anticancer principles from medicinal piper ( hu jiao) plants.
AB  - The ethnomedical uses of Piper ( Hu Jiao) plants as anticancer agents, in vitro
      cytotoxic activity of both extracts and compounds from Piper plants, and in vivo
      antitumor activity and mechanism of action of selected compounds are reviewed in
      the present paper. The genus Piper (Piperaceae) contains approximately 2000
      species, of which 10 species have been used in traditional medicines to treat
      cancer or cancer-like symptoms. Studies have shown that 35 extracts from 24 Piper
      species and 32 compounds from Piper plants possess cytotoxic activity. Amide
      alkaloids account for 53% of the major active principles. Among them, piplartine
      (piperlongumine) shows the most promise, being toxic to dozens of cancer cell
      lines and having excellent in vivo activity. It is worthwhile to conduct further
      anticancer studies both in vitro and in vivo on Piper plants and their active
      principles. 

PMID- 24872929
TI  - Recent scientific studies of a traditional chinese medicine, tea, on prevention
      of chronic diseases.
AB  - Green tea ( Lu Cha), made from the leaves of the plant Camellia sinensis, has
      traditionally been used as a medicine in China for thousands of years. According
      to the classical work of Li Shizhen ( Li Shi Zhen) of the Ming Dynasty, "tea is
      cold and lowers the fire." Since fire (inflammation) causes many diseases, could
      tea be effective in the prevention of many diseases? The possible prevention of
      chronic diseases such as cancer, metabolic syndrome, obesity, diabetes, and
      cardiovascular diseases has been studied with contemporary scientific methods,
      and the results are promising. The molecular mechanisms underlining these
      observations will be discussed in this presentation. One of the reasons for the
      failure to demonstrate a disease-preventive effect of tea in some epidemiological
      studies is the lower quantities of tea consumption in humans. Can we increase the
      quantity of tea consumption to harness its health benefits without causing
      gastrointestinal irritation? This is a topic for further research. 

PMID- 24872932
TI  - Polysaccharides from dioscorea ( shan yao) and other phytochemicals enhance
      antitumor effects induced by DNA vaccine against melanoma.
AB  - Adjuvants can be used to enhance the immunogenicity of antigens and improve the
      efficacy of vaccines. Potent adjuvant action is known to often correlate with the
      activation of the transcription factor, nuclear factor-kappaB (NF-kappaB).
      Specific plant polysaccharides and a variety of phytochemicals from foods and
      traditional medicinal herbs have been shown to modulate NF-kappaB activation. In
      the present study, selected plant polysaccharides and phytochemicals were
      evaluated for use as a DNA vaccine adjuvant in a murine melanoma model. We
      observed that a specific ethanol extract fraction (DsCE-I) from the tuber of a
      key Traditional Chinese Medicine plant, Dioscorea ( Shan Yao), enhanced the
      protection against melanoma after immunization with a gene-based vaccine. A
      number of anti-inflammatory phytochemicals tested were able to partially diminish
      the inflammation-associated tumorigenesis elicited by LPS. Among the several
      phytochemical combinations investigated, the use of an adjuvant containing LPS in
      combination with emodin resulted in smaller tumors and higher survival rate in
      test mice than the use of other adjuvant treatments and the control sets in this
      DNA cancer vaccine model. A Dioscorea polysaccharide fraction (DsCE-I) and
      several specific phytochemicals warrant further exploration as useful adjuvants
      for anticancer vaccines. 

PMID- 24872933
TI  - Exploratory study on the ayurvedic therapeutic management of cerebral palsy in
      children at a tertiary care hospital of karnataka, India.
AB  - Cerebral palsy (CP) is the leading cause of childhood disability affecting
      cognitive function and developments in approximately 1.5 to 3 cases per 1000 live
      births. Based on Ayurvedic therapeutic principles, CP patients were subjected to
      Abhyanga (massage) with Moorchita Tila Taila (processed sesame oil) and Svedana
      (fomentation) with Shastikashali Pinda Sveda (fomentation with bolus of drugs
      prepared with boiled rice). Study group received Mustadi Rajayapana Basti (enema
      with herbal decoction) and Baladi Yoga (a poly-herbo-mineral formulation), while
      the placebo group received Godhuma Vati (tablet prepared with wheat powder) and
      saline water as enema. Treatment with Mustadi Rajayapana Basti and Baladi Yoga
      improved the activities of daily life by 8.79%, gross motor functions by 19.76%,
      and fine motor functions 15.05%, and mental functions like memory retention got
      improved by 15.43%. The placebo group showed an improvement of 0.21% in daily
      life activities, 2.8% in gross motor, and 2.4% in fine motor functions. Mustadi
      Rajayapana Basti and Baladi Yoga proved to be more supportive in improving the
      motor activities and gross behavioral pattern. Further clinical trials are
      required to evaluate and validate the maximum effect of the combination therapy
      in a large sample with repetition of the courses for longer duration. 

PMID- 24872930
TI  - Antiviral natural products and herbal medicines.
AB  - Viral infections play an important role in human diseases, and recent outbreaks
      in the advent of globalization and ease of travel have underscored their
      prevention as a critical issue in safeguarding public health. Despite the
      progress made in immunization and drug development, many viruses lack preventive
      vaccines and efficient antiviral therapies, which are often beset by the
      generation of viral escape mutants. Thus, identifying novel antiviral drugs is of
      critical importance and natural products are an excellent source for such
      discoveries. In this mini-review, we summarize the antiviral effects reported for
      several natural products and herbal medicines. 

PMID- 24872931
TI  - Type 1 diabetes, cardiovascular complications and sesame ( zhi ma).
AB  - Diabetes is a major concern among medical practitioners, with the annual
      mortality rate increasing up to 26.9% in a person aged 65 years or older and
      11.3% in the adult. There are many serious complications associated with
      diabetes, particularly cardiovascular complications due to microvascular
      diseases. A prerequisite to reduce the risk of microvascular and neurologic
      complications of type 1 diabetes is normoglycemia. Insulin therapy is the most
      common treatment used nowadays in type 1 diabetes. However, this method still has
      many disadvantages such as increased episode of severe hypoglycemia, hypoglycemia
      unawareness, increased weight gain, transient exacerbation of pre-existing
      retinopathy, etc. Using insulin pump (the insulin pump is a medical device used
      for continuous subcutaneous insulin infusion to manage the insulin level in the
      treatment of diabetes mellitus), is associated with known disadvantages including
      increased ketoacidosis, infection at the infusion site, and the treatment being
      less suitable in young children (less than 7 years of age). Therefore,
      alternative treatment for diabetes is still in great demand. We took the approach
      of traditional Chinese medicine to discuss this matter. Sesame ( Zhi Ma), a herb,
      has been used medicinally for thousands of years in almost all the countries in
      the world. The beneficial effects of sesame in remediating diabetes, such as
      hypoglycemic effects, antioxidant, anti-inflammatory, and hypolipidemic effects,
      improving fat metabolism, and reducing cholesterol, have been demonstrated in
      many studies,. However, reports on the effects of sesame in remediating
      cardiovascular complications in diabetic patients are limited, which necessitates
      further studies on the effects of sesame on cardiovascular complications. 

PMID- 24872934
TI  - The Fruiting Bodies, Submerged Culture Biomass, and Acidic Polysaccharide
      Glucuronoxylomannan of Yellow Brain Mushroom Tremella mesenterica Modulate the
      Immunity of Peripheral Blood Leukocytes and Splenocytes in Rats with Impaired
      Glucose Tolerance.
AB  - The prevalence of diabetes mellitus (DM), a chronic disease with hyperglycemia
      and impaired immune function, is increasing worldwide. Progression from impaired
      glucose tolerance (IGT) to type 2 DM has recently become a target for early
      intervention. The fruiting bodies (FB) and submerged culture mycelium (CM) of
      Tremella mesenterica, an edible and medicinal mushroom, have been demonstrated to
      have antihyperglycemic and immunomodulatory activities in type 1 DM rats. Herein,
      we investigated the effects of acidic polysaccharide glucuronoxylomannan (GX)
      extracted from CM on the immunocyte responses. Male Wistar rats were injected
      with streptozotocin (65 mg/kg) plus nicotinamide (200 mg/kg) for the induction of
      IGT, and gavaged daily with vehicle, FB, CM, or GX (1 g/kg/day). Rats injected
      with saline and gavaged vehicle were used as controls. Two weeks later,
      peripheral blood leukocytes (PBLs) and splenocytes were collected. Ingestion of
      FB, CM, and GX significantly decreased blood glucose levels in the postprandial
      period and in oral glucose tolerance test, and partially reversed T-splenocytic
      proliferation in IGT rats. CM significantly decreased T-helper lymphocytes in the
      PBLs and B-splenocytes. In addition, FB, CM, and GX significantly reversed the
      IGT-induced decreases in tumor necrosis factor-alpha production; GX significantly
      increased interleukin-6 production in T-lymphocytes in the PBLs and splenocytes;
      and CM and GX significantly reversed IGT-induced decrease in interferon-gamma
      production in T-lymphocytes in the spleen. In conclusion, FB, CM, and acidic
      polysaccharide GX of T. mesenterica may increase T-cell immunity via the
      elevation of proinflammatory and T-helper cytokine production in rats with
      impaired glucose tolerance. 

PMID- 24872935
TI  - Protective Effects of N-acetylcysteine and a Prostaglandin E1 Analog,
      Alprostadil, Against Hepatic Ischemia: Reperfusion Injury in Rats.
AB  - Ischemia-reperfusion (I/R) injury has a complex pathophysiology resulting from a
      number of contributing factors. Therefore, it is difficult to achieve effective
      treatment or protection by individually targeting the mediators or mechanisms.
      Our aim was to analyze the individual and combined effects of N-acetylcysteine
      (NAC) and the prostaglandin E1 (PGE1) analog alprostadil on hepatic I/R injury in
      rats. Thirty male Sprague-Dawley rats were randomly divided into five groups (six
      rats per group) as follows: Control group, I/R group, I/R + NAC group, I/R +
      alprostadil group, and I/R + NAC + alprostadil group. The rats received
      injections of NAC (150 mg/kg) and/or alprostadil (0.05 MUg/kg) over a period of
      30 min prior to ischemia. These rats were then subjected to 60 min of hepatic
      ischemia followed by a 60-min reperfusion period. Hepatic superoxide dismutase
      (SOD), catalase, and glutathione levels were significantly decreased as a result
      of I/R injury, but they were increased in groups treated with NAC. Hepatic
      malondialdehyde (MDA), myeloperoxidase (MPO), and nitric oxide (NO) activities
      were significantly increased after I/R injury, but they were decreased in the
      groups with NAC treatment. Alprostadil decreased NO production, but had no effect
      on MDA and MPO. Histological results showed that both NAC and alprostadil were
      effective in improving liver tissue morphology during I/R injury. Although NAC
      and alprostadil did not have a synergistic effect, our findings suggest that
      treatment with either NAC or alprostadil has benefits for ameliorating hepatic
      I/R injury. 

PMID- 24872936
TI  - Pumpkin Seed Oil Extracted From Cucurbita maxima Improves Urinary Disorder in
      Human Overactive Bladder.
AB  - The pumpkin seed oil obtained from Cucurbita pepo has been shown to be useful for
      the treatment of nocturia in patients with urinal disorders in several western
      countries. In this study, we evaluated the effect of the pumpkin seed oil from
      Cucurbita maxima on urinary dysfunction in human overactive bladder (OAB). Forty
      five subjects were enrolled in this study. An extract of pumpkin seed oil from C.
      maxima (10 g of oil/day) was orally administrated for 12 weeks. After 6 and 12
      weeks, urinary function was evaluated using Overactive Bladder Symptom Score
      (OABSS). Pumpkin seed oil from C. maxima significantly reduced the degree of
      OABSS in the subjects. The results from our study suggest that pumpkin seed oil
      extracts from C. maxima as well as from C. pepo are effective for urinary
      disorders such as OAB in humans. 

PMID- 24872937
TI  - Influence of flocculating agents and structural vehicles on the physical
      stability and rheological behavior of nitrofurantoin suspension.
AB  - BACKGROUND: Nitrofurantoin is a nitrofuran antibiotic that has been used for
      treatment of urinary tract against positive and negative bacteria. OBJECTIVES:
      The aim of this study was to evaluate the effect of structural vehicles and
      flocculating agents on physical stability and rheological behavior of
      nitrofurantoin suspension. MATERIALS AND METHODS: To formulate the suspensions,
      the effect of glycerin and polysorbate 80 as wetting agents was evaluated and
      their particle sizes were determined using the sieve method. Then to achieve
      controlled flocculation, sodium citrate and aluminum chloride were added. After
      choosing the suitable wetting and flocculating agents, structural vehicles such
      as sodium carboxyl methyl cellulose and Veegum were evaluated individually and in
      combination. In addition, the effect of sorbitol on density of continuous phase
      and some physical stability parameters such as sedimentation volume, degree of
      flocculation and ease of redispersion of the suspensions were evaluated. After
      incorporation of structural vehicles, the rheological properties of formulations
      were also determined to find their flow behavior. RESULTS: According to the
      results, glycerin (0.2%) and sodium citrate (0.3%) had the best effect on the
      suspension stability as wetting and flocculating agents, respectively.
      Rheological properties of formulations showed pseudoplastic behavior with some
      degree of thixotropy. CONCLUSIONS: In conclusion, the suspension containing
      Veegum 1%, sodium carboxy methyl cellulose 1%, glycerine 0.2%, sodium citrate
      0.3% and sorbitol 20 % was chosen as the most physically stable formulation.

PMID- 24872938
TI  - Berberis Fruit Extract and Biochemical Parameters in Patients With Type II
      Diabetes.
AB  - BACKGROUND: Diabetes mellitus is a common medical problem. There is in fact a
      growing body of literature on plants used for the treatment of diabetes. Plant
      materials attracted considerable interest of scientists. In this respect, in the
      past few years, attempts were made to use natural plant products for the
      treatment of patients with diabetes. OBJECTIVES: The aim of this study was to
      investigate the effect of Berberis fruit extract to achieve glycemic control in
      patients with Type II diabetes. MATERIALS AND METHODS: This study was performed
      between July 2010 and April 2013. Thirty patients of type II diabetes admitted to
      Ayatollah Rohhani hospital were recruited. Patients' sera were collected for the
      assessment of glucose and HbA1c values. Biochemical analyses were performed
      before and after treatment by Berberis fruit extract. Biochemical parameters were
      measured by spectrophotometric method (Jenway uv/vis, 6505 model, Dunmow, UK).
      Glucose level was measured by glucose oxidase method kit (Pars Azmoon, Tehran, IR
      Iran). Serum total cholesterol and triglycerides were measured using standard
      biochemical kits (Pars Azmoon, Tehran, Iran). Blood glycated hemoglobin level was
      measured by using Elisa kit (Bioassay technology laboratory, Elisa kit).
      Experiments were performed in triplicate in at least three separate experiments.
      RESULTS: Our findings demonstrated that patients with type 2 diabetes who
      received barberry fruit had significant reduction in serum glucose to 136.15 +/-
      32.8 mg/dL and decreased HbA1c levels to 7.07 +/- 1.21 mg/dL, during the 8 weeks
      of study. CONCLUSIONS: This investigation revealed that Berberis fruit extract
      has beneficial metabolic effects in patients with type II diabetes. Barberry may
      improve glucose catabolism via glycolysis pathway, stimulate insulin secretion or
      improve insulin function and finally decrease glucose uptake. Our results
      indicated that Berberis fruit regulates glucose metabolism in patients with type
      2 diabetes.

PMID- 24872939
TI  - T-2 toxin Analysis in Poultry and Cattle Feedstuff.
AB  - BACKGROUND: T-2 toxin is a mycotoxin that is produced by the Fusarium fungi.
      Consumption of food and feed contaminated with T-2 toxin causes diseases in
      humans and animals. OBJECTIVES: In this study T-2 toxin was analyzed in poultry
      and cattle feedstuff in cities of Mazandaran province (Babol, Sari, Chalus),
      Northern Iran. MATERIALS AND METHODS: In this study, 90 samples were analyzed for
      T-2 toxin contamination by the ELISA method. RESULTS: Out of 60 concentrate and
      bagasse samples collected from various cities of Mazandaran province, 11.7% and
      3.3% were contaminated with T-2 toxin at concentrations > 25 and 50 ug/kg,
      respectively. For mixed poultry diets, while 10% of the 30 analyzed samples were
      contaminated with > 25 ug/kg, none of the tested samples contained T-2 toxin at
      levels > 50 ug/kg. CONCLUSIONS: The results obtained from this study show that
      poultry and cattle feedstuff can be contaminated with different amounts of T-2
      toxin in different conditions and locations. Feedstuff that are contaminated by
      this toxin cause different diseases in animals; thus, potential transfer of
      mycotoxins to edible by-products from animals fed mycotoxin-contaminated feeds
      drives the need to routinely monitor mycotoxins in animal feeds and their
      components. This is the basis on which effective management of mycotoxins and
      their effects can be implemented.

PMID- 24872940
TI  - Chlorhexidine digluconate effects on planktonic growth and biofilm formation in
      some field isolates of animal bacterial pathogens.
AB  - BACKGROUND: To study chlorhexidine digluconate disinfectant effects on planktonic
      growth and biofilm formation in some bacterial field isolates from animals.
      OBJECTIVES: The current study investigated chlorhexidine digluconate effects on
      planktonic growth and biofilm formation in some field isolates of veterinary
      bacterial pathogens. MATERIALS AND METHODS: Forty clinical isolates of
      Escherichia coli, Salmonella serotypes, Staphylococcus. aureus and Streptococcus
      agalactiae (10 isolates for each) were examined for chlorhexidine digluconate
      effects on biofilm formation and planktonic growth using microtiter plates. In
      all of the examined strains in the presence of chlorhexidine digluconate, biofilm
      development and planktonic growth were affected at the same concentrations of the
      disinfectant. RESULTS: Chlorhexidine digluconate inhibited the planktonic growth
      of different bacterial species at sub-MICs. But they were able to induce biofilm
      development of the E. coli, Salmonella spp., S. aureus and Str. agalactiae
      strains. CONCLUSIONS: Bacterial resistance against chlorhexidine is increasing.
      Sub-MIC doses of chlorhexidine digluconate can stimulate the formation of biofilm
      strains.

PMID- 24872941
TI  - Detection of Antiseptic-Resistance Genes in Pseudomonas and Acinetobacter spp.
      Isolated From Burn Patients.
AB  - BACKGROUND: Quaternary ammonium compounds (QAC), which contain benzalkonium
      chloride as the most widely used agent, are employed as wound and skin
      antiseptics, as well as disinfectants in hospitals. The resistance mechanism to
      disinfectants is usually determine by genes which are related to resistance to
      quaternary ammonium compounds, namely, qacE, qacDeltaE1, qacDeltaE1 that are
      found in Gram-negative bacteria. OBJECTIVES: The aim of this study was to
      determine the incidence of antiseptic resistance genes, qacE and qacDeltaE1, in
      clinical isolates of Pseudomonas aeruginosa and Acinetobacter bumanii. MATERIALS
      AND METHODS: In this study, 83 clinical isolates of Pseudomonas aeruginosa, and 5
      isolates of Acinetobacter baumannii from burn hospitals in Tehran and Isfahan
      provinces in 2010-2011, were tested by the PCR method. RESULTS: Out of the 83
      clinical isolates of Pseudomonas aeruginosa, 49 isolates (50%) had the qacE gene,
      and 76 isolates (91.5%) had the qacDeltaE1 gene. In addition, in 5 isolates of
      Acinetobacter bumanii, 2 isolates (40%) had the qacE gene, and 4 isolates (80%)
      had the qacDeltaE1 gene. CONCLUSIONS: This study shows that the genes which
      harbored resistance to quaternary ammonium compound antiseptics are widespread
      among Pseudomonas aeruginosa and Acinetobacter bumanii isolates in burn patients.

PMID- 24872942
TI  - Effect of Aqueous Allium cepa and Ixora brachiata Root Extract on Leishmania
      major Promastigotes.
AB  - BACKGROUND: Leishmaniasis is a major worldwide public health problem with about
      two to three million humans threatened by this disease annually. Allium cepa
      (onion) is an important dietary vegetable and was used as a herbal medicine for
      centuries. The root of Ixora brachiata is medicinally important. OBJECTIVES: The
      aim of this study was to investigate the anti-Leishmania effect of the ethanolic
      and methanolic extracts of Ixora brachiata root and aqueous onion extracts on
      Leishmania major promastigotes. PATIENTS AND METHODS: The parasites isolated from
      cutaneous leishmaniasis were exposed with different concentrations of selected
      plant extracts and their inhibitory effects on the promastigotes were evaluated
      after 24 and 48 hours. RESULTS: Among tested plant extracts, Ixora brachiata root
      extracts revealed the best activity against Leishmania major promastigotes with
      IC100 value of 2.5 mg/mL and IC50 value of 0.078 mg/mL. CONCLUSIONS: This study
      showed that aqueous Allium cepa and Ixora brachiata root extracts as natural
      products could be used as alternative drugs in treatment of leishmaniasis.

PMID- 24872943
TI  - Mercury removal from aqueous solutions with chitosan-coated magnetite
      nanoparticles optimized using the box-behnken design.
AB  - BACKGROUND: Nowadays, removal of heavy metals from the environment is an
      important problem due to their toxicity. OBJECTIVES: In this study, a modified
      method was used to synthesize chitosan-coated magnetite nanoparticles (CCMN) to
      be used as a low cost and nontoxic adsorbent. CCMN was then employed to remove
      Hg(2+) from water solutions. MATERIALS AND METHODS: To remove the highest
      percentage of mercury ions, the Box-Behnken model of response surface methodology
      (RSM) was applied to simultaneously optimize all parameters affecting the
      adsorption process. Studied parameters of the process were pH (5-8), initial
      metal concentration (2-8 mg/L), and the amount of damped adsorbent (0.25-0.75 g).
      A second-order mathematical model was developed using regression analysis of
      experimental data obtained from 15 batch runs. RESULTS: The optimal conditions
      predicted by the model were pH = 5, initial concentration of mercury ions = 6.2
      mg/L, and the amount of damped adsorbent = 0.67 g. Confirmatory testing was
      performed and the maximum percentage of Hg(2+) removed was found to be 99.91%.
      Kinetic studies of the adsorption process specified the efficiency of the pseudo
      second-order kinetic model. The adsorption isotherm was well-fitted to both the
      Langmuir and Freundlich models. CONCLUSIONS: CCMN as an excellent adsorbent could
      remove the mercury ions from water solutions at low and moderate concentrations,
      which is the usual amount found in environment.

PMID- 24872944
TI  - Development, characterizations and biocompatibility evaluations of intravitreal
      lipid implants.
AB  - BACKGROUND: The treatment of posterior eye diseases is always challenging mainly
      due to inaccessibility of the region. Many drugs are currently delivered by
      repeated intraocular injections. OBJECTIVES: The purpose of this study was to
      investigate the potential applications of natural triglycerides as alternative
      carriers to synthetic polymers in terms of drug release profile and also
      biocompatibility for intraocular use. MATERIALS AND METHODS: In vitro/in vivo
      evaluations of intravitreal implants fabricated from the physiological lipid,
      glyceride tripalmitate containing clindamycin phosphate as a model drug was
      performed. The micro-implants with average diameter of 0.4 mm were fabricated via
      a hot melt extrusion method. The extrudates were analyzed using scanning electron
      microscopy, differential scanning calorimetry, and in vitro drug dissolution
      studies. For biocompatibility, the implants were implanted into rabbit eyes.
      Clinical investigations including fundus observations, electroretinography as
      well as histological evaluations were performed. RESULTS: In vitro tests
      guaranteed usefulness of the production method for preparing the homogenous
      mixture of the drug and lipid without affecting thermal and crystalinity
      characteristics of the components. In vitro releases indicated a bi-phasic
      pattern for lower lipid ratios, which were completed by the end of day three.
      With higher lipid ratios, more controlled release profiles were achieved until
      about ten days for a lipid ratio of 95%. Clinical observations did not show any
      abnormalities up to two months after implantation into the rabbit eye.
      CONCLUSIONS: These results suggest that although the implant could not adequately
      retard release of the present drug model yet, due to good physical
      characteristics and in vivo biocompatibility, it can represent a suitable device
      for loading wide ranges of therapeutics in treatment of many kinds of
      retinochoroidal disorders.

PMID- 24872945
TI  - Protective Effects of Crocin on Ischemia-reperfusion Induced Oxidative Stress in
      Comparison With Vitamin E in Isolated Rat Hearts.
AB  - BACKGROUND: Myocardial Injury caused by ischemia-reperfusion leads to cardiac
      dysfunction, tissue injury and metabolic changes. The production of reactive
      oxygen species (ROS) and lipid peroxidation are accompanied by ischemia
      reperfusion injury. OBJECTIVES: The aim of this study was to assess the cardio
      protective potential effects of crocin in comparison with vitamin E on
      antioxidant capacity in ischemia-reperfusion of isolated rat hearts. MATERIALS
      AND METHODS: Seventy male Sprague-Dawley rats were randomly divided into seven
      groups, including: sham, control and experimental groups treated with different
      doses of crocin (10, 20 and 40 mg/kg) or vitamin E (100 mg/kg) and a combination
      of crocin (40 mg/kg) with vitamin E (100 mg/kg) that were administrated orally
      for 21 days. The heart was quickly excised, transferred to a Langendorff
      apparatus at constant pressure and subjected to 30 minutes of global ischemia
      followed by 60 minutes of reperfusion. Cardiac damage markers and antioxidant
      enzymes were measured. RESULTS: The results showed that superoxide dismutase and
      catalase enzyme activities increased and Mallon de aldehyde (MDA) decreased in
      animals pretreated by crocin (40 mg/kg) and vitamin E (100 mg/kg). Moreover,
      there was a significant improvement in post ischemic recovery of antioxidant
      capacity during reperfusion in rats receiving a combination of crocin (40 mg/kg)
      and vitamin E (100 mg/kg). CONCLUSIONS: The results demonstrated the protective
      role of crocin on antioxidant capacity, which may partially be related to
      stability or amplification of antioxidant systems. Like vitamin E, crocin may be
      beneficial for prevention or treatment of cardiac dysfunction and myocardial
      infarction in patients with ischemic heart disease.

PMID- 24872946
TI  - Persian gulf bioactive natural drugs.

PMID- 24872947
TI  - Effect of oxidative stress on male reproduction.
AB  - Infertility affects approximately 15% of couples trying to conceive, and a male
      factor contributes to roughly half of these cases. Oxidative stress (OS) has been
      identified as one of the many mediators of male infertility by causing sperm
      dysfunction. OS is a state related to increased cellular damage triggered by
      oxygen and oxygen-derived free radicals known as reactive oxygen species (ROS).
      During this process, augmented production of ROS overwhelms the body's
      antioxidant defenses. While small amounts of ROS are required for normal sperm
      functioning, disproportionate levels can negatively impact the quality of
      spermatozoa and impair their overall fertilizing capacity. OS has been identified
      as an area of great attention because ROS and their metabolites can attack DNA,
      lipids, and proteins; alter enzymatic systems; produce irreparable alterations;
      cause cell death; and ultimately, lead to a decline in the semen parameters
      associated with male infertility. This review highlights the mechanisms of ROS
      production, the physiological and pathophysiological roles of ROS in relation to
      the male reproductive system, and recent advances in diagnostic methods; it also
      explores the benefits of using antioxidants in a clinical setting. 

PMID- 24872948
TI  - Mirodenafil for the treatment of erectile dysfunction: a systematic review of the
      literature.
AB  - Phosphodiesterase type 5 (PDE5) inhibitors are the most commonly used treatment
      for erectile dysfunction (ED). Since the launch of sildenafil, several drugs
      including mirodenafil, sildenafil citrate (sildenafil), tadalafil, vardenafil HCL
      (vardenafil), udenafil, and avanafil-have become available. Mirodenafil is a
      newly developed pyrrolopyrimidinone compound, which is a potent, reversible, and
      selective oral PDE5 inhibitor. Mirodenafil was launched in Korea in 2007, and an
      orally disintegrating film of mirodenafil was developed in 2011 for benefitting
      patients having difficulty in swallowing tablets. This study aimed to review the
      pharmacokinetic characteristic profile of mirodenafil and report evidence on its
      efficacy in the case of ED. In addition, we reviewed randomized controlled
      studies of mirodenafil's daily administration and efficacy for lower urinary
      tract symptoms. 

PMID- 24872949
TI  - The Efficacy and Safety of Tadalafil 5 mg Once Daily in Korean Men with Lower
      Urinary Tract Symptoms Suggestive of Benign Prostatic Hyperplasia: An Integrated
      Analysis.
AB  - PURPOSE: This post hoc integrated analysis assessed the efficacy and safety of
      tadalafil 5 mg once daily in a large Korean population with lower urinary tract
      symptoms suggestive of benign prostatic hyperplasia (BPH-LUTS). MATERIALS AND
      METHODS: Individual Korean participant data were integrated from three 12-week,
      randomized, double-blind, placebo-controlled studies in Asian men with BPH-LUTS,
      wherein 177 Korean men received placebo and 177 received tadalafil 5 mg once
      daily. The primary objective was to compare the change from baseline to week 12
      in total International Prostate Symptom Score (IPSS) after treatment with
      tadalafil versus placebo. RESULTS: A significantly greater improvement (p<0.001)
      in total IPSS from baseline to week 12 was observed for tadalafil compared to
      placebo (least squares mean: tadalafil=-5.97; placebo=-3.94 ). Total IPSS at
      weeks 4 and 12, IPSS voiding and storage subscores at weeks 4, 8, and 12, and
      IPSS quality of life index at weeks 8 and 12 were also significantly improved
      (p<0.05) for tadalafil compared to placebo. There was significant improvement
      (p<0.001) in the patient global Impression of improvement responses and numerical
      improvement in the clinician global impression of improvement responses with
      tadalafil compared to placebo. There were no significant treatment differences
      for peak urine flow rate or postvoid residual volume. Few participants had
      treatment-emergent adverse events and there were no unexpected safety findings.
      CONCLUSIONS: This integrated analysis of three randomized, placebo-controlled
      Asian studies confirmed tadalafil 5 mg once daily as an efficacious and well
      tolerated treatment for Korean men with BPH-LUTS.

PMID- 24872950
TI  - Sympathetic skin response in patients with vascular erectile dysfunction.
AB  - PURPOSE: We aimed to investigate the utility of sympathetic skin response (SSR)
      test for evaluating vasculogenic erectile dysfunction (ED) which is the most
      common type of impotence. MATERIALS AND METHODS: Men in the age group of 28 to 60
      years and suffering from vasculogenic ED, as confirmed by a papaverin test and
      color Doppler sonography, at least for 6 months referred from our university
      urology department were included. We used the International Index of Erectile
      Function (IIEF-5) for grading severity of dysfunction and recorded the SSR of
      every patient from the median, tibial, and dorsal nerves of the penis. One-way
      analysis of variance (ANOVA), independent t-test and Pearson's correlation
      coefficient were used for comparing quantitative variables, and Fisher's Exact
      test was used for comparing qualitative variables. The Mann-Whitney U Test and
      the Kruskal-Wallis test were performed for analysis of data that were not
      normally distributed. A p value of less than 0.05 was considered significant.
      RESULTS: Forty-two patients were recruited for the study. We found a strong
      statistical relationship between the IIEF score and the pathologic SSR registered
      from every mentioned nerve. Patients with abnormal SSR had more severe ED
      according to IIEF score (p<0.001). In addition, the IIEF score had a
      significantcorrelation with diabetes mellitus and cardiovascular disease (t-test;
      p<0.05). CONCLUSIONS: Our results confirmed the presence of autonomic dysfunction
      in patients with vasculogenic impotence via an SSR test. We suggest evaluating
      the efficacy of the SSR test in patients with vascular impotence for treatment
      response monitoring in future studies.

PMID- 24872951
TI  - Testicular Biopsy Histopathology as an Indicator of Successful Restoration of
      Spermatogenesis after Varicocelectomy in Non-obstructive Azoospermia.
AB  - PURPOSE: We aimed to evaluate the efficacy of using testicular biopsy
      histopathology as an indicator of the success of loupe-assisted subinguinal
      varicocelectomy in non-obstructive azoospermia (NOA) patients. MATERIALS AND
      METHODS: In a 2-year period, a prospective study was carried at Minoufiya
      University Hospital on 20 NOA patients with clinical bilateral varicoceles. These
      patients underwent loupe-assisted subinguinal varicocelectomy with simultaneous
      testicular biopsy. All patients were evaluated by determining their hormonal
      profile and performing semen analyses and scrotal Doppler and transrectal
      ultrasonography. Two semen analyses showing azoospermia were performed before the
      surgery and two semen analyses were received at 3 and 6 months post-operatively
      for follow-up. RESULTS: The mean age was 29.9+/-6.7 years, and the mean follow-up
      duration was 17.3+/-8.3 months. We noted the restoration of spermatogenesis in
      six men (30% of all patients). Testicular biopsy results were as follows:
      hypospermatogenesis in 7 patients, maturation arrest in 3, and Sertoli cell-only
      syndrome in 10. The improvement in the sperm counts of these patients ranged from
      3 million to 15 million/mL. Sperms were recovered in the hypospermatogenesis (6
      patients, 85.5%) patients only, but other patients with testicular biopsy results
      of Sertoli cell-only or maturation arrest did not show any improvement in their
      semen parameters. CONCLUSIONS: Testicular biopsy results showed that
      hypospermatogenesis patients have a better chance of improvement in their semen
      analysis after varicocelectomy in contrast to NOA patients with Sertoli cell-only
      syndrome or maturation arrest.

PMID- 24872952
TI  - Is semen analysis necessary for varicocele patients in their early 20s?
AB  - PURPOSE: To determine whether it is necessary to analyze the semen of varicocele
      patients in their early 20s who are not complaining of infertility. MATERIALS AND
      METHODS: Data was collected retrospectively from 128 men with varicocele with no
      complaint of infertility, but with complaints of pain/discomfort or a
      mass/swelling during a 4-year period beginning in January 2009. The varicocele
      cases were matched 4 : 1 by age to 32 hemospermia controls. RESULTS: The median
      patient age was 22.0 years in the case group and 24.0 years in the control group.
      The median values of the percentage of normal motility, normal morphology, and
      density in the case group were 42.5%, 40.0%, and 51.0*10(6)/mL, respectively. The
      median serum testosterone level was 4.2 ng/mL and 7.0% of the total patients had
      low serum testosterone levels in the case group. The number of patients with
      asthenospermia (17.2%), oligospermia (10.9%), and teratospermia (5.5%), and those
      with at least one abnormal semen parameter (19.5%) was significantly higher in
      the case group than the control group. The median values of the motility,
      morphology, and density of the case group were significantly lower than those of
      the control group. The multivariate analysis showed that patient characteristics
      (age, presence of pain, duration of symptoms, and grade of varicocele) cannot
      help to predict abnormal semen parameters (asthenospermia, oligospermia,
      teratospermia, or cases of at least 1 abnormal semen parameter) or serum
      testosterone levels <3.0 ng/mL. CONCLUSIONS: Semen analysis is required as a
      screening test for semen abnormalities regardless of the chief complaint in
      varicocele patients in their early 20s.

PMID- 24872953
TI  - The incidence of Fever after subinguinal microsurgical varicocelectomy.
AB  - PURPOSE: In the present study, we aimed to identify the incidence of fever in
      patients after subinguinal microsurgical varicocelectomy and to evaluate the
      clinical factors associated with the occurrence of the fever. MATERIALS AND
      METHODS: We retrospectively reviewed the cases of patients who underwent
      subinguinal microsurgical varicocelectomy (group A) under spinal anesthesia. In
      addition, we reviewed the cases of patients who underwent microsurgical
      vasovasostomy under spinal anesthesia as a control group (group B). The incidence
      of fever in each group was compared. We investigated the clinical factors
      influencing the occurrence of fever in the patients of group A. RESULTS: The
      incidence of fever in group A was significantly higher than that in group B
      (32.5% [53/163] vs. 0.4% [1/284]; p<0.001). Clinical factors such as age,
      varicocele grade, weight, height, operation time, number of ligated veins, usage
      of immediate postoperative analgesics, presence of postoperative hematoma, and
      duration of hospital stay were not significantly associated with the occurrence
      of fever. CONCLUSIONS: We found that one-third of the patients developed
      transient fever after subinguinal microsurgical varicocelectomy, and therefore,
      this information should be provided during preoperative counseling.

PMID- 24872954
TI  - The role of imaging in the diagnosis of recurrence of primary seminal vesicle
      adenocarcinoma.
AB  - Primary seminal vesicle (SV) adenocarcinoma is a rare tumor. A small amount of
      data about the role of imaging to detect tumor recurrence is available. We report
      the case of a 58-year-old patient with primary SV clear-cell well-differentiated
      adenocarcinoma. Clinical and instrumental examinations were negative for the 32
      months after treatments when computed tomography scan, [(18)F]fluoro-D-glucose
      positron emission tomography/computed tomography and pelvic magnetic resonance
      imaging showed the appearance of a lesion in the left perineal muscle suspected
      for recurrence. Patient was symptomless. Cytology of the suspected lesion
      confirmed SV adenocarcinoma recurrence. The combined approach, using radiological
      and nuclear medicine techniques, seems to be effective in the follow-up of SV
      adenocarcinoma. Technological advances, together with awareness of this rare
      tumor, have the potential of improving patients outcomes not only by providing
      earlier detection and accurate staging, but also by detecting recurrence and
      thereby avoiding delays and therapeutic dilemmas. 

PMID- 24872955
TI  - Necrosis of the penis with multiple vessel atherosclerosis.
AB  - Penile necrosis is a very rare complication because of its rich collateral
      supply. Conservative management is apt to be ineffective; thus penectomy is
      usually performed. We present a case of penile necrosis and claudication of both
      legs with multiple atherosclerosis in a type II diabetes mellitus patient who was
      successfully treated with angioplasty, penoplasty, and additional intracavernous
      injections of prostaglandin E1. The treatment resulted in relief of the leg pain
      and healing of the penile ischemic lesions. 

PMID- 24872956
TI  - Humoral autoimmune responses to insulin-like growth factor II mRNA-binding
      proteins IMP1 and p62/IMP2 in ovarian cancer.
AB  - Ovarian cancer is one of the leading causes of cancer-related deaths among women.
      There is an urgent need of better approaches for the identification of
      appropriate biomarkers in the early detection of ovarian cancer. The aim of this
      study was to elucidate the significance of autoantibodies against insulin-like
      growth factor II mRNA-binding proteins (IMPs) in patients with ovarian cancer. In
      this study, autoantibody responses to two members (IMP1 and p62/IMP2) of IMPs
      were evaluated by enzyme-linked immunosorbent assay (ELISA), western blotting,
      and indirect immunofluorescence assay in sera from patients with ovarian cancer
      and normal human individuals. The results have demonstrated that both IMP1 and
      p62/IMP2 can induce relatively higher frequency of autoantibody responses in
      patients with ovarian cancer (26.5% and 29.4%) compared to normal individuals
      (P<0.01). Our preliminary data suggest that IMP1 and p62/IMP2 can stimulate
      autoimmune responses in ovarian cancer, and anti-IMP1 and anti-p62/IMP2
      autoantibodies could be used as potential biomarkers in immunodiagnosis of
      ovarian cancer.

PMID- 24872959
TI  - The role of TH17-associated cytokines in health and disease.

PMID- 24872957
TI  - Identification of osteosarcoma-related specific proteins in serum samples using
      surface-enhanced laser desorption/ionization-time-of-flight mass spectrometry.
AB  - Osteosarcoma (OS) is the most common malignant bone tumor. To identify OS-related
      specific proteins for early diagnosis of OS, a novel approach, surface-enhanced
      laser desorption/ionization-time-of-flight mass spectrometry (SELDI-TOF-MS) to
      serum samples from 25 OS patients, 16 osteochondroma, and 26 age-matched normal
      human volunteers as controls, was performed. Two proteins showed a significantly
      different expression in OS serum samples from control groups. Proteomic profiles
      and external leave-one-out cross-validation analysis showed that the correct rate
      of allocation, the sensitivity, and the specificity of diagnosis were 100%. These
      two proteins were further identified by searching the EPO-KB database, and one of
      the proteins identified as Serine rich region profile is involved in various
      cellular signaling cascades and tumor genesis. The presence of these two proteins
      in OS patients but absence from premalignant and normal human controls implied
      that they can be potential biomarkers for early diagnosis of OS. 

PMID- 24872960
TI  - Renal markers in normal and hypertensive disorders of pregnancy in Indian women:
      a pilot study.
AB  - BACKGROUND: Altered renal function is an essential component of the
      pathophysiological process in pre-eclampsia. Kidneys play an important role in
      the turnover of low molecular weight substances such as creatinine, uric acid and
      cystatin C. The present study was undertaken if these serum markers were
      characteristically altered in Indian pregnant women. METHODS: Serum levels were
      therefore determined in samples from 69 healthy women at term as well as in 27
      samples of patients with Pregnancy induced hypertension (PIH) and in 20 patients
      with pre-eclampsia (PE). RESULTS: The levels of all three components were
      significantly higher in pre-eclamptic patients when compared to healthy controls
      with the mean +/- SD being 1.47 +/- 0.9 vs. 1.06 +/- 0.2 for cystatin C, 0.95 +/-
      0.2 vs. 0.67 +/- 0.1 for creatinine and 6.13 +/- 1.8 vs. 4.28 +/-1.1 for uric
      acid respectively. In PIH cystatin C was significantly higher, 1.25 +/- 0.9
      unlike creatinine, 0.67 +/- 0.14 and uric acid, 4.30 +/- 1.0. Receiver operating
      characteristic (ROC) plots demonstrated that the diagnostic accuracy of serum
      creatinine was superior to serum uric acid and serum cystatin C and serum uric
      acid was better than serum cystatin C. CONCLUSION: The maternal serum cystatin C,
      creatinine and uric acid were all significantly elevated at the end of pregnancy
      in pre-eclampsia compared to those of healthy pregnant women. If this rise in the
      above markers during early pregnancy could predict the onset of PIH/PE, needs to
      be investigated.

PMID- 24872958
TI  - The Treg/Th17 paradigm in lung cancer.
AB  - Pathogenic mechanisms underlying the development of lung cancer are very complex
      and not yet entirely clarified. T lymphocytes and their immune-regulatory
      cytokines play a pivotal role in controlling tumor growth and metastasis.
      Following activation by unique cytokines, CD4+ T helper cells differentiate into
      Th1, Th2, Th17, and regulatory T cells (Tregs). Traditionally, research in lung
      cancer immunity has focused almost exclusively on Th1/Th2 cell balance. Recently,
      Th17 cells and Tregs represent an intriguing issue to be addressed in lung cancer
      pathogenesis. Tregs play an important role in the preservation of self-tolerance
      and modulation of overall immune responses against tumor cells. Th17 cells
      directly or via other proinflammatory cytokines modulate antitumor immune
      responses. Notably, there is a close relation between Tregs and Th17 cells.
      However, the possible interaction between these subsets in lung cancer remains to
      be elucidated. In this setting, targeting Treg/Th17 balance for therapeutic
      purposes may represent a useful tool for lung cancer treatment in the future. The
      purpose of this review is to discuss recent findings of the role of these novel
      populations in lung cancer immunity and to highlight the pleiotropic effects of
      these subsets on the development and regulation of lung cancer. 

PMID- 24872993
TI  - Bladder cancer: gender disparities may delay diagnosis in women.

PMID- 24872961
TI  - Identification of serum proteome components associated with progression of non
      small cell lung cancer.
AB  - The aim of the present study was to perform comparative analysis of serum from
      patients with different stages of non-small cell lung cancer (NSCLC) using the
      three complementary proteomic approaches to identify proteome components
      associated with the progression of cancer. Serum samples were collected before
      any treatment from 200 patients with NSCLC, including 103 early stage, 64 locally
      advanced and 33 metastatic cancer samples, and from 200 donors without
      malignancy. The low-molecular-weight fraction of serum proteome was MALDI
      profiled in all samples. Serum proteins were characterized using 2D-PAGE and LC
      MS/MS approaches in a representative group of 30 donors. Several significant
      differences were detected between serum samples collected from patients with
      early stage cancer and patients with locally advanced cancer, as well as between
      patients with metastatic cancer and patients with local disease. Of note, serum
      components discriminating samples from early stage cancer and healthy persons
      were also detected. In general, about 70 differentiating serum proteins were
      identified, including inflammatory and acute phase proteins already reported to
      be associated with the progression of lung cancer (serum amyloid A or
      haptoglobin). Several differentiating proteins, including apolipoprotein H or
      apolipoprotein A1, were not previously associated with NSCLC. No significant
      differences in patterns of serum proteome components were detected between
      patients with adenocarcinoma and squamous cell carcinoma. In conclusion, we
      identified the biomarker candidates with potential importance for molecular
      proteomic staging of NSCLC. Additionally, several serum proteome components
      revealed their potential applicability in early detection of the lung cancer. 

PMID- 24872994
TI  - Take a stand and stop sitting so much.

PMID- 24872995
TI  - Skin cream do's and don'ts for eczema.

PMID- 24872996
TI  - I'm taking six different drugs to manage my blood pressure, cholesterol and
      diabetes. Should I be concerned about driving?.

PMID- 24872997
TI  - I just had colon surgery and am worried about adhesions. What can I do?

PMID- 24872998
TI  - I'm being treated for breast cancer. Is it all right to exercise?

PMID- 24872999
TI  - Zap away your migraine.

PMID- 24873000
TI  - Another PPI precaution.

PMID- 24873001
TI  - Keep an eye out for diabetic vision damage.

PMID- 24873003
TI  - Ask the doctor. Is it okay to take both aspirin and ibuprofen therapies?

PMID- 24873002
TI  - Easy ways to protect your mobility. Ask these two questions to find out if you're
      at risk of losing mobility and independence.

PMID- 24873004
TI  - Ask the doctor. Do PPI drugs for stomach acid reduce the risk of cancer in people
      (like me) with Barrett's esophagus?

PMID- 24873005
TI  - Drug-free options to fight depression.  Cognitive behavioral therapy, exercise,
      and magnetic stimulation can make a difference.

PMID- 24873006
TI  - Great exercise that's easier on the joints.  Aquatic therapy can reduce pain and
      pressure while providing an effective workout.

PMID- 24873007
TI  - 5 simple steps that may help prevent colorectal cancer.  Screenings, exercise,
      and vitamin D may reduce your risks.

PMID- 24873008
TI  - Tips for healthy food on the go.  Batch cooking, smoothies, and lots of planning
      pay off when you're in a hurry.

PMID- 24873009
TI  - Get a better night's sleep by turning off electronic gadgets.  Make 9 p.m. your
      cutoff time, and keep screens off if you wake in the night.

PMID- 24873010
TI  - Is this common blood pressure drug risky? Some evidence suggests calcium-channel
      blockers have an association with breast cancer and kidney problems.

PMID- 24873011
TI  - Strengthen your muscles to reduce diabetes risk.

PMID- 24873012
TI  - Mediterranean diet now linked to reduced risk of PAD.

PMID- 24873013
TI  - Sit more, live less, warn Harvard researchers.

PMID- 24873014
TI  - [Professor Luis Alvarez: in memoriam].

PMID- 24873015
TI  - [Statins in CIN: a problem at least partly solved?].

PMID- 24873016
TI  - Preface. Role of reviews. Environmental Contamination and Toxicology.

PMID- 24873017
TI  - Called to care for foundlings, orphans, unwanted and abused children: St.
      Vincent's Infant Asylum, 1881-1972.

PMID- 24873018
TI  - Administrative detention of drugs intended for human or animal use. Final rule.
AB  - The Food and Drug Administration (FDA or the Agency) is implementing
      administrative detention authority with respect to drugs intended for human or
      animal use as authorized by amendments made to the Federal Food, Drug, and
      Cosmetic Act (the FD&C Act) by the Food and Drug Administration Safety and
      Innovation Act (FDASIA). FDA's administrative detention authority with respect to
      drugs allows FDA to better protect the integrity of the drug supply chain.
      Specifically, FDA is able to administratively detain drugs encountered during an
      inspection that an authorized FDA representative conducting an inspection has
      reason to believe are adulterated or misbranded. This authority is intended to
      protect the public by preventing distribution or subsequent use of drugs
      encountered during inspections that are believed to be adulterated or misbranded,
      until FDA has had time to consider what action it should take concerning the
      drugs, and to initiate legal action, if appropriate.

PMID- 24873019
TI  - Medical devices; gastroenterology-urology devices; classification of pancreatic
      drainage stent and delivery system. Final order.
AB  - The Food and Drug Administration (FDA) is classifying the pancreatic drainage
      stent and delivery system into class II (special controls). The special controls
      that will apply to the device are identified in this order, and will be part of
      the codified language for the pancreatic drainage stent and delivery system
      classification. The Agency is classifying the device into class II (special
      controls) in order to provide a reasonable assurance of safety and effectiveness
      of the device.

PMID- 24873020
TI  - The articles in this issue consider the costs measurement of mental disorders in
      Germany. Introduction.

PMID- 24873021
TI  - The prevalence and prevention of crosstalk: a multi-institutional study.
AB  - It is a common problem in psychology subject pools for past study participants to
      inform future participants of key experimental details (also known as crosstalk).
      Previous research (Edlund, Sagarin, Skowronski, Johnson, & Kutter, 2009)
      demonstrated that a combined classroom and laboratory treatment could
      significantly reduce crosstalk. The present investigation tested a laboratory
      only treatment for the prevention of crosstalk at five universities, along with
      institutional-level moderators of crosstalk. Results indicated the presence of
      crosstalk at all universities and that the laboratory-based treatment was
      effective in reducing crosstalk. Importantly, crosstalk rates were higher (but
      successfully neutralized) in research pools with higher research credit
      requirements. Therefore, this research provides valuable guidance regarding
      crosstalk prevalence and its minimization by researchers.

PMID- 24873022
TI  - An electrophysiological investigation of the effects of social rejection on self
      control.
AB  - Previous studies have shown that social rejection leads to impaired performance
      on a variety of tasks that require self control, including the Stroop color-word
      interference task; however, mechanisms underlying the effect remain to be
      elucidated. We attempted to clarify the effects of social rejection on self
      control resources by measuring event-related potentials (ERPs) during a
      computerized Stroop test. Stroop performance and ERPs from 54 participants in
      rejected, control, and accepted groups were analyzed. A significant difference in
      the pattern of results for the N450 ERP was found, with rejected participants
      showing less negativity on incongruent trials and more on congruent trials
      compared to accepted participants and controls. The results suggest social
      rejection reduces the engagement of cognitive control mechanisms, and are more
      consistent with a limited strength resource model than with limited capacity
      resource models that focus on limitations in attention.

PMID- 24873023
TI  - Identity and the theory of planned behavior: predicting maintenance of
      volunteering after three years.
AB  - Is identity an important predictor of social behavior? The present longitudinal
      study is focused on identity in order to understand why people continue to
      volunteer over an extended period of time. The theory of planned behavior and the
      role identity model of volunteering are used as theoretical framework. Two
      hundred thirty Italian volunteers were sampled and followed for 3 years. We
      analyzed functions of role identity as a volunteer. Results showed a significant
      impact of role identity in predicting volunteer performance after 3 years,
      mediated through behavioral intentions. Role identity fully mediated the
      relationships between behavioral intention and attitude, social norms, past
      behavior and parental modelling.

PMID- 24873024
TI  - Orders to shoot (a camera): effects of ostracism on obedience.
AB  - Research suggests that ostracism increases susceptibility to indirect forms of
      social influence (e.g., conformity). Yet, no study to date has explored whether
      the effects of ostracism extend to the most direct form of social influence-
      obedience. We investigated whether ostracized individuals would be more likely to
      obey a direct command to do something effortful in uncomfortable conditions.
      Participants (N = 62) were randomly assigned to be included or ostracized in
      Cyberball, or assigned to a control condition. They were then approached by the
      experimenter and commanded to go outside when temperatures were below 30 degrees
      F and take 39 unique and creative photographs in the cold of winter. Ostracized
      participants were more likely to obey the experimenter's command to be creative
      when taking photographs. No differences in obedience emerged between the
      inclusion and the control condition. We provided evidence completing the social
      influence "trifecta": ostracism increases susceptibility to conformity,
      compliance, and now, obedience.

PMID- 24873025
TI  - Intergroup contact and prejudice against people with schizophrenia.
AB  - There is a growing awareness that responses to mental health disorders differ
      according to the label. Still, research on contact and prejudice against people
      with mental health disorders has generally focused on the broader label, "mental
      illness," as though various disorders were interchangeable. The present research
      specifically investigated the relationship between intergroup contact and
      avoidance of people with schizophrenia--a particularly stigmatized and
      challenging group--as well as mediators of that relationship. In Study 1, 78
      students completed measures of their prior contact with and prejudice against
      people with schizophrenia. Prior contact predicted less desired avoidance of
      people with schizophrenia, and this relationship was mediated by more favorable
      attitudes. Study 2 (N = 122) replicated the results of Study 1, and also found
      that less fear and less intergroup anxiety mediated the relationship between
      contact and avoidance. This suggests that contact may effectively reduce
      prejudice, even against this highly stigmatized group.

PMID- 24873026
TI  - Reactions to intragroup deviance: does disidentification have a role?
AB  - In this study, we address previous evidence about the interchangeable use of
      derogation and disidentification in protecting the self from intragroup deviance.
      We argue that when the in-group stands for a valued social identity, members may
      disidentify from the group, but only if the immediate context provides no
      opportunity to derogate. In the present experiments (n = 80 and n = 79), we
      provided or did not provide participants with the opportunity to recommend a
      punishment for an in-group or an out-group deviant. We also measured in-group
      identification before and after exposure to deviant behavior and after judgment.
      The results show that participants first disidentified from the in-group but,
      when presented with an opportunity to judge the deviant, also derogated.
      Importantly, participants who could judge the deviant also recovered their
      initial in-group identification level. Participants' reactions to the out-group
      deviant suggest they used an intergroup rather than intragroup strategy.

PMID- 24873028
TI  - A new ergostane triterpenoid from a solid culture of the basidiomycete Inocybe
      lilacina.
AB  - A new and rare ergostane triterpenoid, 4alpha-methyl-3alpha,4beta-dihydroxy
      ergost-8,24(28)-dien-7,11-dion-25-al (1), was isolated from cultures of the
      basidiomycete Inocybe lilacina, and its structure established on the basis of
      spectral methods (MS, IR, 1D and 2D NMR).

PMID- 24873027
TI  - Justice orientation as a moderator of the framing effect on procedural justice
      perception.
AB  - Justice orientation is a justice-relevant personality trait, which is referred to
      as the tendency to attend to fairness issues and to internalize justice as a
      moral virtue. This study examined the moderating role of justice orientation in
      the relationship between justice perception and response to a decision problem.
      The authors manipulated procedural justice and the outcome valence of the
      decision frame within a vignette, and measured justice orientation of 174
      Japanese participants. As hypothesized, the results indicated an interaction
      between procedural justice and framing manipulation, which was moderated by
      individual differences in justice orientation. In negative framing, justice
      effects were larger for individuals with high rather than low justice
      orientation. The results are explained from a social justice perspective, and the
      contributions and limitations of this study are also discussed with respect to
      our sample and framing manipulation.

PMID- 24873029
TI  - Non-alkaloidal compounds from the bulbs of the Egyptian plant Pancratium
      maritimum.
AB  - Phytochemical investigation of the cytotoxic fractions of fresh bulbs of
      Pancratium maritimum L. led to the isolation and structure identification of two
      new compounds, pancricin (1) and pancrichromone (4), together with four known
      compounds, including 2,4-dihydroxy-6-methoxy-3-methyl acetophenone (2), 5
      formylfurfuryl acetate (3), 7-beta-D-glucosyloxy-5-hydroxy-2-methylchromone (5),
      and ethyl-beta-D-glucopyranoside (6). Their structures were established on the
      basis of 1D and 2D NMR spectroscopy (1H, 13C, COSY, HSQC, and HMBC), as well as
      HR mass spectral analyses. The compounds were evaluated for their antimigratory
      and antiproliferative activities against the highly metastatic human prostate
      cancer cell line (PC-3M). Compound 5 was the most active compound displaying good
      activity in the proliferation assay comparable to that of the positive control 4
      hydroxyphenylmethylene hydantoin, while it displayed only weak antimigratory
      activity compared to the positive control 4-ethylmercaptophenylmethylene
      hydantoin.

PMID- 24873030
TI  - In vitro investigation of anticancer, cell-cycle-inhibitory, and apoptosis
      inducing effects of diversin, a natural prenylated coumarin, on bladder carcinoma
      cells.
AB  - Chemotherapy is one of the main strategies for reducing the rate of cancer
      progression or, in some cases, curing the tumour. Since a great number of
      chemotherapeutic agents are cytotoxic compounds, i. e. similarly affect normal
      and neoplastic cells, application of antitumour drugs is preferred in cancer
      management and therapy. In this study, the cytotoxicity of diversin was evaluated
      in 5637 cells, a transitional cell carcinoma (TCC) subline (bladder carcinoma),
      and normal human fibroblast cells using the 3-(4,5-dimethyl-2-thiazolyl)-2,5
      diphenyl-2H-tetrazolium bromide (MTT) assay. Chromatin condensation and DNA
      damage induced by diversin were also determined by means of 4',6-diamidino-2
      phenylindole (DAPI) staining and the comet assay, respectively. In addition, the
      mechanism of action of diversin was studied in more detail by the caspase 3
      colourimetric assay and flow cytometry-based cell-cycle analyses (PI staining).
      Our results revealed that diversin has considerable cytotoxic effects in 5637
      cells, but not on HFF3 (human foreskin fibroblast) and HDF1 (human dermal
      fibroblast) cells. Further studies showed that diversin exerts its cytotoxicity
      via induction of chromatin condensation, DNA damage, and activation of caspase 3
      in 5637 cells. In addition, flow cytometric analyses revealed that 5637 cells are
      mostly arrested at the G2 phase of the cell cycle in the presence of diversin.

PMID- 24873031
TI  - Antileishmanial compounds from Moringa oleifera Lam.
AB  - The antileishmanial activity of extracts and phytoconstituents of Moringa
      oleifera Lam. was investigated in vitro against promastigotes of Leishmania
      donavani. The 70% ethanolic extract of roots and the methanolic extract of leaves
      showed moderate inhibitory activity with IC50 values of 83.0 microg/ml and 47.5
      microg/ml, respectively. Antileishmanial activity of the methanolic extract of
      leaves increased upon fractionation, as its ethyl acetate fraction was found to
      be more active with an IC50 value of 27.5 microg/ml. The most active
      antileishmanial compound niazinin, a thiocarbamate glycoside isolated from this
      fraction, showed an IC50 value of 5.25 microM. Results presented in this study
      indicate that extracts from M. oleifera may be developed as an adjuvant therapy
      for the treatment of leishmaniasis.

PMID- 24873032
TI  - Cytotoxic polyacetylenes from the Red Sea sponge Siphonochalina siphonella.
AB  - Two new polyacetylenes, callyspongenol-D (1) and callyspongendiol (2), the known
      polyacetylene dehydrosiphonochalynol (3), and the known triterpenoid sipholenol-A
      (4) were isolated from the Red Sea sponge Siphonochalina siphonella. Their
      chemical structures were elucidated on the basis of spectroscopic analyses. The
      cytotoxicity of the isolated compounds towards the human mammary carcinoma cell
      line MCF-7 was determined by the lactate dehydrogenase (LDH) assay, and compounds
      4 and 1 were found to be the most toxic of the four, with IC50 values of 8.8 and
      11.7 microM, respectively.

PMID- 24873033
TI  - The co-occurrence of two pyridine alkaloids, mimosine and trigonelline, in
      Leucaena leucocephala.
AB  - Leucaena leucocephala is a nitrogen-fixing tropical leguminous tree that produces
      two pyridine alkaloids, i. e. mimosine [beta-(3-hydroxy-4-pyridon-1-yl)-L
      alanine] and trigonelline (1-methylpyridinium-3-carboxylate). Mimosine has been
      detected in leaves, flowers, pods, seeds, and roots, and it is one of the
      principal non-protein amino acids that occurs in all organs. Asparagine was the
      most abundant amino acid in flowers. The mimosine content varied from 3.3
      micromol/g fresh weight (FW) in developing flowers to 171 micromol/g FW in mature
      seeds. Trigonelline was also detected in leaves, flowers, pods, and seeds, but
      not roots. The trigonelline content was lower than that of mimosine in all
      organs. It varied from 0.12 micromol/g FW in developing seeds to 2.6 micromol/g
      FW in mature seeds. [2-14C]Nicotinic acid supplied to the developing seeds was
      incorporated into trigonelline but not mimosine. This indicates that the pyridine
      and dihydroxypyridine structures of these two alkaloids are derived from distinct
      precursors. The physiological functions of mimosine and trigonelline are
      discussed briefly.

PMID- 24873034
TI  - Aqueous garlic extract alleviates liver fibrosis and renal dysfunction in bile
      duct-ligated rats.
AB  - There is accumulating evidence that the renin-angiotensin system (RAS) is
      involved in hepatic inflammation and fibrogenesis. Garlic was found to lower the
      activity of the angiotensin converting enzyme (ACE) in the serum of rats in a
      diabetic model. We examined the effect of an aqueous garlic extract (AGE) on the
      ACE activity, cholestasis-induced liver fibrosis, and associated renal
      dysfunction in comparison with the effect of the standard drug enalapril. Both
      AGE and enalapril were administered orally for six weeks starting from the third
      day after bile duct ligation (BDL). BDL significantly increased the serum
      activities of liver enzymes, serum lactate dehydrogenase (LDH) activity, an
      indicator of liver cell death, serum total bilirubin (TB) level, liver
      myeloperoxidase (MPO) activity, and liver malondialdehyde (MDA) content. BDL was
      associated with elevation of serum urea and creatinine levels indicating renal
      dysfunction. BDL also caused an increase in the transcript levels of the genes
      coding for tumour necrosis factor alpha (TNF-alpha), transforming growth factor
      beta-1 (TGF-beta1), and matrix metalloproteinase-13 (MMP-13), a collagenase, in
      liver tissues. A significant decrease in hepatic reduced glutathione (GSH) was
      observed in BDL rats, while serum ACE activity was increased. Both AGE and
      enalapril counteracted all these deleterious changes, with the exception that
      only AGE reduced the MPO activity. These findings suggest that AGE possesses
      hepato- and renoprotective properties, similar to enalapril, probably by
      modulating the levels of proteins such as TNF-alpha, TGF-beta1 and MMP-13, and
      involving a reduction of ACE and of oxidative stress.

PMID- 24873035
TI  - The wheat aquaporin gene TaAQP7 confers tolerance to cold stress in transgenic
      tobacco.
AB  - Aquaporin proteins (AQPs) have been shown to be involved in abiotic stress
      responses. However, the precise role of AQPs, especially in response to cold
      stress, is not understood in wheat (Triticum aestivum). In the present study,
      quantitative real time polymerase chain reaction (qRT-PCR) analysis revealed that
      TaAQP7 expression increased in leaves, but decreased in roots after cold
      treatment. Expression of TaAQP7 in tobacco plants resulted in increased root
      elongation and better growth compared with wild-type (WT) plants under cold
      stress. Moreover, after cold treatment, the transgenic tobacco lines exhibited
      higher chlorophyll contents, lower levels of malondialdehyde (MDA), and less ion
      leakage (IL) than WT plants. Thus, expression of TaAQP7 enhanced cold stress
      tolerance in transgenic tobacco. Taken together, our results suggest that TaAQP7
      confers cold stress tolerance by relieving membrane damage in the transgenic
      plants.

PMID- 24873036
TI  - Isolation and characterization of wild-type lipoxygenase LOX(Psa)1 from Pleurotus
      sapidus.
AB  - The lipoxygenase LOX(Psa) 1 of Pleurotus sapidus, originally investigated because
      of its ability to oxidize (+)-valencene to the valuable grapefruit aroma (+)
      nootkatone, was isolated from the peptidase-rich lyophilisate using a three-step
      purification scheme including preparative isoelectric focusing and
      chromatographic techniques. Nano-liquid chromatography electrospray ionization
      tandem mass spectrometry (nLC-ESI-MS/MS) of the purified enzyme and peptide mass
      fingerprint analysis gave 38 peptides of the lipoxygenase from P. sapidus. Nearly
      50% of the 643 amino acids long sequence encoded by the cDNA was covered. Both
      terminal peptides of the native LOX(Psa) 1 were identified by de novo sequencing,
      and the postulated molecular mass of 72.5 kDa was confirmed. With linoleic acid
      as the substrate, the LOX(Psa)1 showed a specific activity of 113 U mg(-1) and
      maximal activity at pH 7.0 and 30 degrees C, respectively.

PMID- 24873037
TI  - Molecular cloning and characterization of a Bombyx mori gene encoding the
      transcription factor Atonal.
AB  - The atonal genes are an evolutionarily conserved group of genes encoding
      regulatory basic helix-loop-helix (bHLH) transcription factors. These
      transcription factors have a critical antioncogenic function in the retina, and
      are necessary for cell fate determination through the regulation of the cell
      signal pathway. In this study, the atonal gene was cloned from Bombyx mori, and
      the transcription factor was named BmAtonal. Sequence analysis showed that the
      BmAtonal protein shares extensive homology with other invertebrate Atonal
      proteins with the bHLH motif. Reverse transcription-polymerase chain reaction (RT
      PCR) and Western blot analyses revealed that BmAtonal was expressed in all
      developmental stages of B. mori and various larval tissues. The BmAtonal protein
      was expressed in Escherichia coli, and polyclonal antibodies were raised against
      the purified protein. By immunofluorescence, the BmAtonal protein was localized
      to both the nucleus and cytoplasm of BmN cells. After knocking out nuclear
      localization signals (NLS), the BmAtonal protein was only detected in the
      cytoplasm. In addition, using the B. mori nuclear polyhedrosis virus (BmNPV)
      baculovirus expression system, the recombinant BmAtonal protein was successfully
      expressed in the B. mori cell line BmN. This work lays the foundation for
      exploring the biological functions of the BmAtonal protein, such as identifying
      its potential binding partners and understanding the molecular control of the
      formation of sensory organs.

PMID- 24873038
TI  - Total antioxidant capacity of feces of mammalian herbivores and carnivores.
AB  - The total antioxidant capacities (TAC) of feces of mammalian herbivores and
      carnivores were compared. TAC were estimated using three different methods: 2,2'
      azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical (ABTS*) reduction, 1,1
      diphenyl-2-picrylhydrazyl radical (DPPH*) reduction, and ferric reducing
      antioxidant power (FRAP). TAC of 18 herbivorous species were generally higher
      with respect to 16 carnivorous species [(14.21 +/- 6.72) vs. (9.45 +/- 7.32) mmol
      Trolox equivalents/kg feces; P < 0.05] in the FRAP assay. The ABTS* reduction
      assay indicated that the TAC originating from "fast" reacting antioxidants were
      higher in the herbivores than in carnivores [(17.92 +/- 7.18) vs. (12.22 +/- 8.5)
      mmol Trolox equivalents/kg feces; P < 0.05], while a reverse trend was observed
      for TAC originating from "slowly" reacting antioxidants [(20.68 +/- 4.85) vs.
      (24.68 +/- 6.87) mmol Trolox equivalents/kg feces].

PMID- 24873039
TI  - Direct asymmetric aldol reactions catalyzed by lipase from porcine pancreas.
AB  - Porcine pancreas lipase type II (PPL II) exhibited unnatural catalytic activity
      in direct asymmetric aldol reactions between cyclic ketones and aromatic or
      heteroaromatic aldehydes in acetonitrile in the presence of phosphate buffer. A
      wide range of substrates was accepted by the enzyme to afford the corresponding
      aldol products in low to high yields (10-98%), with moderate to excellent
      enantioselectivities (53-94% ee, for anti-isomers) and low to moderate
      diastereoselectivities (48/52-87/13 dr, anti/syn). This methodology expands the
      application of PPL II, and it might be developed into a potentially valuable
      method for sustainable organic synthesis.

PMID- 24873040
TI  - Are midwives valued?

PMID- 24873041
TI  - Evidence builds for new report.

PMID- 24873042
TI  - The RCM needs you!

PMID- 24873043
TI  - Protect against flu.

PMID- 24873045
TI  - No shame in 'student'.

PMID- 24873044
TI  - Blossoming relationships.

PMID- 24873046
TI  - A similar experience.

PMID- 24873047
TI  - Disappointing show.

PMID- 24873048
TI  - A man 'with woman'.

PMID- 24873049
TI  - Perinatal outcomes in women with high BMI.

PMID- 24873050
TI  - How to ... perform an episiotomy.

PMID- 24873052
TI  - Forget me not.

PMID- 24873051
TI  - Exposing the cracks. Has the NMC crumbled beyond repair?

PMID- 24873053
TI  - A weighty issue.

PMID- 24873055
TI  - Releasing the postnatal pressure.

PMID- 24873054
TI  - A 'fresh eyes approach'.

PMID- 24873056
TI  - A high risk reality.

PMID- 24873057
TI  - Inspiring innovation.

PMID- 24873058
TI  - What we say and do.

PMID- 24873060
TI  - The changing face of Wales.

PMID- 24873059
TI  - Last chance saloon.

PMID- 24873061
TI  - Bouncing back.

PMID- 24873062
TI  - Survey post-MDG agenda.

PMID- 24873063
TI  - Foundlings UK.

PMID- 24873064
TI  - A learning curve.

PMID- 24873065
TI  - The birth of the epidural.

PMID- 24873066
TI  - Three pillars of support.

PMID- 24873067
TI  - Age intervention and adverse outcomes.

PMID- 24873068
TI  - How to make critiquing easy.

PMID- 24873070
TI  - A look at life.

PMID- 24873069
TI  - A balancing act.

PMID- 24873071
TI  - Award-winning bereavement care.

PMID- 24873072
TI  - The mountain midwives.

PMID- 24873073
TI  - Spiritual support.

PMID- 24873074
TI  - The burden of shame and stigma.

PMID- 24873075
TI  - Support for the most vulnerable.

PMID- 24873076
TI  - Improving Scotland's maternity care.

PMID- 24873077
TI  - Tongue-tied.

PMID- 24873078
TI  - Animal models for acquired heterotopic ossification.
AB  - Heterotopic ossification (HO), the ectopic formation of bone in soft tissues, is
      a relevant musculoskeletal disorder that, by reduction of range of motion, may
      lead to significant impairment of quality of live. HO can either be acquired or
      hereditary. Acquired HO is seen most often after hip prosthetic surgery and
      pelvic trauma. In contrast, hereditary HO is commonly observed in the axial
      skeleton, but can affect every joint. Substantial effort has been directed
      towards understanding the pathophysiology and towards finding both, effective
      prophylactic and therapeutic treatments. Every improvement of the understanding
      of the pathophysiologic changes underlying HO as well as the rationale of
      prophylactic and therapeutic treatment regimens in the end, is based on the study
      of appropriate animal models. Although intriguing models of 'genetic' HO have
      been developed recently, their relevance to acquired HO remains questionable. As
      there is still neither proper treatment nor reliable prophylaxis, animal models
      will remain important in the study of HO. Currently, there are 6 different animal
      models regularly used for the study of acquired HO. Some of these models can
      reflect a merely particular part of the disease. Hence, selection of the
      appropriate animal model for the study of HO is exceedingly important. The
      present paper reviews the history and major features of the different animal
      models of acquired HO, and reveals some of the insights gained through the study
      of animal models; important biochemical and pathophysiological key features are
      highlighted. Clinical studies have proved indometacine, celecoxib and radiation
      therapy to be effective in reducing the occurrence of HO, but not always be able
      to prevent it.

PMID- 24873080
TI  - The significance of interleukin-6 and lactate in the synovial fluid for
      diagnosing native septic arthritis.
AB  - Aim of this study was to evaluate the role of synovial interleukin-6 and synovial
      lactate for predicting native septic arthritis. We analyzed retrospectively
      synovial fluid parameters (interleukin-6, total-protein, glucose, lactate,
      synovial-fluid-white-blood-cell-count) of 62 patients with culture-verified
      native septic arthritis and compared them to 57 patients with acute aseptic
      arthritis. Receiver-Operating-Characteristic-curves were calculated to determine
      the 'Area-under-the-curves' (AUC), the best thresholds and the corresponding
      likelihood-ratios. The best parameter for diagnosing septic arthritis was
      synovial lactate (AUC = 0.864, sensitivity = 74.5%, specificity = 87.2%),
      followed by synovial interleukin-6 (AUC = 0.803, sensitivity = 92.5%, specificity
      = 64.1%) and the synovial-fluid-white-blood-cell-count (AUC = 0.782, sensitivity
      = 71.2%, specificity = 84.9%). Synovial lactate levels above 10 mmol/l almost
      proofed septic arthritis (interval-Likelihood-Ratio = 20.4), synovial interleukin
      6 levels lower than 7000 pg/ml almost ruled out infection (interval-Likelihood
      Ratio = 0.12). If none of these thresholds are met, physicians should estimate
      disease probability by the simultaneous use of the interval-Likelihood-Ratios of
      synovial lactate, synovial interleukin-6 and synovial-fluid-white-blood-cell
      count.

PMID- 24873079
TI  - The impact of platelet-rich plasma on chronic synovitis in hemophilia.
AB  - Untreated chronic haemophiliac synovitis leads to the development of haemophilic
      arthropathy (HA) by affecting the metabolism of chondrocytes. Symptoms are
      progressive and often surgical intervention is required to prevent total loss of
      joint function. The focus of our study was to influence the chronic haemophiliac
      synovitis by means of autologous platelet-rich plasma (PRP) injection. Six
      patients with hemophilia (PWH), aged between 9 and 45 and manifesting chronic
      synovitis of the ankle joint on one or on both sides (8 joints in total) were
      included into the PRP-study. The patients were classified depending on their
      joint status using the Hemophilia Joint Health Score (HJHS) prior to and again
      two months after treatment. Three to five ml of PRP was injected into the joint
      cavity within 30 seconds. In all of the tested PWH pain relief has been reported
      subjectively by means of the HJHS and VAS scoring systems, comparing the pain
      intensity before PRP injection and two months after. The difference of pain
      perception has been found statistically significant for the VAS-scores.
      Considering the objective synovitis signs shown on MRI before and after PRP
      injection we recorded a decrease in the volume of free synovial fluid after PRP.
      All of the tested patients reported benefit of the PRP therapy.

PMID- 24873081
TI  - Does the wedge wing in the neck screw prevent cut-out failure in Ota/AO 31-A2
      trochanteric fractures in elderly patients?
AB  - The purpose of this retrospective study was to evaluate the effects of Dyna
      Locking Trochanteric (DLT) nail (U & I Corporation 529-1, Yonghyun-dong, Uijungbu
      Kyunggi-Do, Korea 480-050) in 31-A1 and 31-A2 intertrochanteric femur fractures.
      Eighty-seven patients (63 female and 24 male, mean age 77 years) were treated.
      The mean duration of followup was 16.6 +/- 3.1 months (range, 12-24 months).
      There were 36 cases of 31-A1 and 51 cases of 31-A2 fractures. The duration of
      surgery, fluoroscopy screening time, the blood loss, the hospital stay, the tip
      apex distance were significantly less in the 31-A1 fracture group compared with
      the 31-A2 fracture group (p < 0.001). Cut-out was observed in 13 patients (14.9%)
      above 80 years old with 31-A2 fractures. Especially in elderly patients with
      unstable 31-A2 fractures, the wedge wing on the neck screw does not work
      properly. Therefore further biomechanical investigations and also prospective
      clinical studies with larger series are needed to improve the device.

PMID- 24873082
TI  - Risk factors associated with the early failure of cannulated hip screws.
AB  - AIM: We report our experience with cannulated hip screws and analyse the risk
      factors associated with their early failure. MATERIALS AND METHODS: All patients
      undergoing cannulated hip screws at a single UK Major Trauma Centre between
      November 2009 and November 2011 were retrospectively identified. Radiographs were
      analysed for fracture displacement, successful reduction, and screw
      configuration. Risk factors predicting early failure, defined as re-operation
      within 6 months, were identified using logistic regression models. RESULTS: 340
      patients were included in the study, 70% were female and the mean age was 81
      years. After six months 23% patients had undergone revision surgery. Initial
      fracture displacement (p = 0.02) and unsuccessful lateral reduction (p = 0.04)
      were significant predictors of early failure. CONCLUSION: Initial fracture
      displacement and successful fracture reduction are the most important factors
      related to the risk of early re-operation. We found no evidence that screw
      configuration is an important predictor of outcome.

PMID- 24873083
TI  - Results of the learning curve for interventional hip arthroscopy: a prospective
      study.
AB  - This prospective study aims to explore hip arthroscopy, outcome and the effect of
      the learning curve. Using the non-arthritic hip score preoperatively and
      postoperatively in 120 patients with an average 23-month follow-up, a median
      improvement of 16 points was seen at 6 months (p < 0.0001, Wilcoxon's signed
      ranks) remaining at 2 years (15, p < 0.05). Dividing patients into consecutive
      chronological groups of 40, the learning curve was explored. At six-months scores
      improved by 12 (p < 0.05) in first 40, 15 (p < 0.0001) in second and 20 (p <
      0.0001) in third. A reduction in THR (22.5%, 5%, 2.5%) and revision rates (10%,
      7.5%, 0) was seen. An increase in cumulative percentage satisfaction (defined as
      minimum 10 points increase) was seen from 20th (45%) to 100th procedure (65%).
      Results significantly improve as experience increases, possibly due to improved
      surgical skill, preoperative workup or improved understanding of operative
      indications.

PMID- 24873084
TI  - High prevalence of anterolateral ligament abnormalities in magnetic resonance
      images of anterior cruciate ligament-injured knees.
AB  - The purpose of this study was to identify the newly described anterolateral
      ligament of the human knee on magnetic resonance imaging and to describe its
      eventual radiological abnormalities in anterior cruciate ligament-injured
      subjects. A retrospective cohort study on a series of consecutive subjects
      undergoing anterior cruciate ligament reconstructive surgery was performed. The
      MR images of 206 included knees were studied and the status of the anterolateral
      ligament status was judged to be either "non-visualized", "normal" or "abnormal".
      Of all the visualized anterolateral ligaments, 44 (21.3%) were considered
      uninjured, while 162 (78.8%) knees demonstrated radiological ALL abnormalities.
      The majority of ALL abnormalities were situated in the distal part of the
      ligament (77.8%). In conclusion, the anterolateral ligament can be identified on
      classic knee magnetic resonance images. Although anterior cruciate ligament
      injured subjects often demonstrated associated anterolateral ligament lesions,
      further research is needed in order to establish the clinical relevance of these
      highly frequent radiological abnormalities.

PMID- 24873085
TI  - Vascularized fibular transfer in longstanding and infected large bone defects.
AB  - The reconstruction of large bone defects in the infectious environment is still a
      big challenge for limb salvage because of disturbance in bacterial flora,
      bacterial resistance and limitation of blood supply at scarred tissue. This
      retrospective study was to evaluate long-term outcomes in patients who were
      performed vascularized fibular transfers for treatment of large bone defects in
      the infectious environment. The review included 26 patients with an average age
      of 27 years old. Bone defects were located at the arm in 1 patient, the forearm
      in 2 patients, the thigh in 6 patients and the leg in 17 patients. The cause of
      the bone defects included high-energy trauma in 14 cases, chronic osteomyelitis
      in 7 cases, infected non-union in 5 cases. All patients had had several previous
      operative procedures. The average length of fibular vascularized graft was 16.6
      cm (range, 10-22 cm), and the average size of the associated fasciocutaneous
      component in 16 patients was 3.6 x 8.5 cm. Three patients had partial necrosis of
      skin paddle. Three patients, who were stabilized by screw and external fixator,
      had an infection at the distal part of the fibular graft and pin tracts. 25
      fibular grafts (96%) showed complete bone union. This review has showed that the
      vascularized fibular transfer can be effective for management of large segmental
      bone defects in the infectious environment.

PMID- 24873086
TI  - Salter pelvic osteotomy in the treatment of Legg-Calve-Perthes disease: the
      medium-term results.
AB  - In this study, clinical and radiological results were evaluated in patients with
      Legg-Calve-Perthes disease treated with Salter pelvic osteotomy. Between 2004 and
      2008, 16 patients underwent a Salter osteotomy as treatment for Legg-Calve
      Perthes disease (15 male, 1 female; 10 right hip, 6 left hip). The mean age at
      the time of surgery was 8.1 +/- 1.4 (range: 6 to 10) years. Surgical indications
      were : age between 6-10 years at the onset of the disease; Herring classification
      type B, B/C, or C; and at least one risk sign. 6-8 year old patients were
      classified as group I and 9-10 year olds were classified as group II. We
      investigated the effects of age and Herring classification on radiological
      outcomes. The final radiographic evaluation according to the Stulberg
      classification showed nine hips (56.25%) classified as good (Stulberg I/II), five
      (31.25%) as fair (Stulberg III); and two (12.5%) as poor (Stulberg IV). In group
      I, 7 patients (70%) had good results, while only 2 (33.3%) in group II. The
      results in group I were statistically better than group II (p < 0.05). Based on
      the Herring lateral pillar type, of the 12 patients classified as B or B/C, at
      final follow-up, 8 (66.6%) had a good outcome (Stulberg I/II), whereas in the
      four patients classified as type C, only one (25%) had a good outcome. The Salter
      pelvic osteotomy is an effective method of surgical treatment for Legg-Cave
      Perthes in patients between 6-8 years of age.

PMID- 24873087
TI  - Femoral fractures in infants: a comparison of Bryant traction and modified Pavlik
      harness.
AB  - Bryant traction is a commonly used method for femoral shaft fractures in
      children, but many disadvantages have been reported. Pavlik harness with exact
      clinical effect and fewer complications has gained increasing popularity in
      resent years. The objective of this study was to evaluate and compare modified
      Pavlik harness with Bryant traction for infant with a femoral shaft fracture. A
      retrospective study was performed of 38 infants treated with either modified
      Pavlik Harness or Bryant traction. All fractures were closed, isolated, and
      diaphyseal. We analyzed operative and radiographic data, complications, hospital
      charges, and functional outcome. Twenty-one patients, with a mean age of 5.9
      months, were treated with modified Pavlik harnesses. Seventeen infants, with a
      mean age of 6.3 months, were treated with Bryant tractions. All fractures united
      within 3-5 weeks. The two cohorts were similar with respect to age, weight, and
      fracture union time. Four of the seventeen children treated with Bryant tractions
      had a skin complication that needed second intervention. No similar complications
      occurred in the modified Pavlik group (p = 0.03). There was a significant
      difference in hospital stay (modified Pavlik harness 1.4 days versus Bryant
      traction 17.8 days) and hospital charge (modified Pavlik harness 3209 Yuan versus
      Bryant traction 3759 Yuan) (p < 0.001). At one year visit, no difference existed
      between the two groups for standard clinical/functional criteria. There were no
      malunion, nonunion, or rotational deformities. Nor were there any significant
      limb length discrepancies, residual angular deformities.

PMID- 24873088
TI  - Randomized controlled trial comparing stabilization of fresh close femoral shaft
      fractures in children with titanium elastic nail system versus stainless steel
      elastic nail system.
AB  - In vitro mechanical studies have demonstrated equal or superior fixation of
      pediatric femoral fractures with use of titanium elastic nails (TENS) as compared
      with stainless steel elastic nails (SSEN). SSEN are less expensive as compared to
      TENS. However, there are only two studies in the English literature which have
      compared the results of TENS and SSEN in paediatric femoral shaft fracture. The
      present study compares the clinical and radiological outcomes of femoral shaft
      fracture in patients 6-12 years of age, operatively stabilised either by TENS or
      SSEN. 35 children (6-12 years) with closed, post traumatic femoral shaft
      fractures were randomized into two treatment groups. Both groups underwent closed
      reduction internal fixation (CRIF) by either of the implants (TENS OR SSENS) as
      per randomization protocol and followed up for six months. Comparison of clinical
      and radiological outcomes in both the groups was done in terms of time to union
      of fracture and radiological angulations in coronal and sagittal plane. There was
      no significant difference in both groups with respect to fracture site tenderness
      and presence of bridging callus at fracture site at 3 weeks, 6 weeks and 6 months
      follow up (p-value = 1.000). There was no significant difference in radiological
      angulation rate in both groups in the sagittal (p-value = 0.661) as well as in
      the coronal plane (p-value = 0.219) at six month follow up. Both groups showed a
      similar rate of complication, most common being prominent hardware. TENS and
      SSENS are equally effective treatment modalities for paediatric femoral shaft
      fracture with similar rate of complications. However, SSENS is less costly as
      compared to TENS and can be considered as an alternative in a resource
      constrained setup.

PMID- 24873089
TI  - How safe is titanium elastic nail application in the surgical treatment of tibia
      fractures in children?
AB  - Tibia fractures in children are generally treated successfully by conservative
      means. The aim of this study was to evaluate the efficacy and safety of fixation
      using Titanium elastic nails (TEN) in pediatric tibia fractures in which
      conservative measures failed or were deemed inapplicable. In this study, 30
      patients who had tibia fractures and were fixated with TEN between 2007 and 2011
      were analyzed retrospectively. The procedure was performed after poly-trauma in
      six patients, open fracture in seven, reduction loss in twelve, and unsuccessful
      closed reduction in five patients. The number of girls and boys was 3 and 27,
      respectively, with a mean age of 9.8 years. The evaluation criteria of Flynn et
      al. were used in the analysis of the results. The mean follow-up period was 18
      months. The mean period of union was 8 weeks and 14 weeks in closed and open
      fractures, respectively. Epiphyseal damage, rotational deformity, need for
      reintervention, deep infection, implant failure, or recurrent fracture was not
      observed in any case. According to the Flynn evaluation system, 23 cases were
      evaluated as excellent, and 7 as good. Fixation with TEN is an easy, effective,
      and safe method that can be used in tibia fractures that are open, irreducible,
      or with loss of reduction and in cases with accompanying trauma, such as floating
      knee.

PMID- 24873090
TI  - Online radiographic survey of midshaft clavicular fractures: no consensus on
      treatment for displaced fractures.
AB  - The choice of treatment for midshaft clavicular fractures is not straightforward,
      but depends on fracture characteristics such as comminution, angulation and
      displacement. An online survey was conducted amongst trauma and orthopaedic
      surgeons to determine the preferred treatment for midshaft clavicular fractures,
      based on anteroposterior radiographs, for 17 randomly selected displaced or
      comminuted midshaft clavicular fractures. The background and experience of the
      respondents were documented. Data were analyzed using a Generalized Estimating
      Equations (GEE) model. The 102 respondents preferred non-operative treatment more
      frequently for displaced fractures than for comminuted fractures (OR 3.24, 95% CI
      2.55-4.12). Locking plate fixation was more often preferred over other surgical
      modalities for comminuted than for displaced fractures (OR 1.50, 95% CI 1.17
      1.91). In clinical practice, there is no consensus between surgeons on the choice
      of treatment for displaced or comminuted midshaft clavicular fractures. This lack
      of agreement calls for evidence-based treatment guidelines for these fractures.

PMID- 24873091
TI  - Glenoid fractures: a review of pathology, classification, treatment and results.
AB  - Glenoid fractures are rare, and relatively little is known about their mechanism,
      fracture pattern and optimal treatment strategies. The avulsions and rim
      fractures are strongly associated with anterior shoulder dislocations. Fossa
      fractures are mostly seen in high energy trauma patients as direct impact of the
      humeral head against the glenoid fossa. CT-scanning can be very useful in
      diagnosing the extend of injury and relation of humeral head with the main
      fragment of the glenoid. Fracture classification systems, have been designed
      mainly based on trauma mechanism, location and severity of fracture pattern.
      Treatment depends on instability, the degree of displacement and the articular
      surface fragment size, but is conservative in most cases. Due to the increase of
      arthroscopic fixation possibilities, operative treatment may increase. In this
      review, we have tried to summarize the available evidence into a treatment
      algorithm for different types of glenoid fractures. With regard to best
      functional outcome, an anatomical and concentric joint restoration should be the
      goal of treatment. Outcome is generally good in conservative and operative
      treatment, but exact data is difficult to appreciate, due to heterogeneity and
      comorbidities in different studies.

PMID- 24873092
TI  - Reverse shoulder arthroplasty for the treatment of three and four part fractures
      of the proximal humerus in patients older than 75 years old.
AB  - Reverse shoulder arthroplasty is an attractive alternative option in treating
      three- or four-part fractures of the proximal humerus. The main goal of the
      current study was to evaluate the functional and radiographic results after
      primary reverse shoulder arthroplasty of three- or four-part fractures of the
      proximal humerus in patients older than 75 years old. Between 2008 and 2010, 29
      consecutive patients with a three- or four-part fracture of the proximal humerus
      undergoing a reversed shoulder prosthesis were included. There were 16 women and
      13 men, with a mean age of 81 years (range 78 to 85). The dominant arm was
      involved in 18 patients (62%). All of the operations were carried out within 10
      days of the injury. The patients were followed up for a mean of 26 months (range
      10 to 36). The mean postoperative Constant-Murley score at the end of the follow
      up period for each patient (age- and gender-matched) was 73.3% (range 58 to 92%).
      The mean Constant score was 75% in the group of patients with fixation of the
      tuberosities and 72.3% in the patients with no fixation of the tuberosities (p =
      0.06). There was no significant difference in Constant score between patients who
      were operated by the fifth day after the fracture and patients who had an
      operation between the sixth and tenth day after the injury (Constant score of 74%
      and 71%, respectively, p = 0.07). Complications occurred in 12 patients. One
      patient sustained a fracture of the acromion intraoperatively. Four patients
      (13.8%) developed heterotopic ossification. One had a nontraumatic anterior
      dislocation due to wrong retroversion of the glenoid component. Scapular notching
      was observed in six shoulders (20.6%).

PMID- 24873093
TI  - Comparison of tension band wiring and precontoured locking compression plate
      fixation in Mayo type IIA olecranon fractures.
AB  - Aim of the present study was to compare the clinical and radiographic outcome of
      tension band wiring and precontoured locking compression plate fixation in
      patients treated surgically for an isolated olecranon fractures type IIA
      according to the Mayo classification. Of 26 patients presenting with an isolated
      Mayo type IIA olecranon fracture, 13 underwent fixation with a precontoured
      locking compression plate (group A), 13 patients were treated with tension band
      wiring (group B). At a mean follow-up of 43 months, patients were clinically and
      radiographically re-examined using the DASH score, the Mayo Elbow Performance
      score (MEPS) and anteroposterior and lateral radiographs. The mean DASH score was
      14 points in group A and 12.5 points in group B. Regarding the MEPS, 92% of the
      patients in group A achieved a good to excellent results in comparison to 77% in
      group B. No significant differences between the two groups could be detected
      regarding the clinical and radiographic outcome. Implant-related irritations
      requiring hardware removal occurred more frequently in group B (12 vs. 7).
      Procedure and implant related costs were significantly higher in group A. Tension
      band wiring is still a preferable surgical method to treat simple isolated
      olecranon fractures. The patient must be informed that in all likelihood implant
      removal will be required once the fracture has healed. Fixation with precontoured
      locking compression plates does not provide better functional and radiographic
      outcome but is more expensive than tension band wiring.

PMID- 24873094
TI  - Arthroscopic debridement with and without distal ulnar resection in the treatment
      of triangular fibrocartilage complex tears.
AB  - A retrospective survey for debridement with or without wafer distal ulna
      resection was performed. Forty six patients responded to a questionnaire on pain,
      disability and time off work. The mean DASH score decreased from 42 to 28 on
      average. Thirty two patients were satisfied. The pain was considered severe in 12
      patients. There were significant differences in the outcome between debridement
      only and debridement with wafer resection of the distal ulna.

PMID- 24873095
TI  - Which measure should be used to assess the patient's functional outcome after
      distal radius fracture?
AB  - The Disability of the Arm, Shoulder and Hand (DASH) and the Patient-Rated Wrist
      Evaluation (PRWE) scores appear most frequently in the literature when assessing
      functional outcome after distal radius fracture. We aimed to evaluate if the two
      questionnaires correlate. We reviewed 258 cases of adults who sustained a distal
      radius fracture over a one year period. At mean follow-up of 17 months the
      disability of the arm, shoulder and hand (DASH) and the patient-rated wrist
      evaluation (PRWE) scores were recorded. The outcome scores for each group were
      not statistically different (DASH p = 0.86, PRWE p = 0.80). The results of both
      questionnaires correlated strongly (Spearman's coefficient = 0.90). As the DASH
      score is potentially influenced by concomitant upper limb problems we suggest
      that the specific patient rated wrist evaluation (PRWE) be the sole instrument
      for assessing the functional outcome of distal radius fractures. This will reduce
      questionnaire fatigue and standardise the literature.

PMID- 24873096
TI  - Comparison of proximal turndown of central slip combined with suture of lateral
      bands versus free tendon grafting for central slip reconstruction after an open
      finger injury.
AB  - We randomized patients with open finger injury and central slip insertion defects
      into a proximal turn-down group (final n = 28) and a palmaris longus tendon graft
      group (final n = 20). In the proximal turn-down group, the dorsal central slip of
      the extensor tendon in the proximal phalanx was split, leaving it attached
      distally. We turned the strip from proximal to distal and fixed it using the
      distal joint capsule of the proximal interphalangeal joint as the distal
      insertion of reconstruction, and the extended central slips were then fixed to
      the middle phalanx. The dorsal traumatic central slip was stitched with lateral
      bands using 2-0 suture to form a new conjoint tendon. The injured central slip in
      the comparison group was sutured using autogenous palmaris longus tendon and
      fixed in drilled holes in the middle phalanx. Outcomes assessment was performed
      according to Dargan's criteria during postoperative follow-up. Motion range in
      the proximal turndown group was significantly greater than in the graft group (p
      < 0.05). We observed no boutonniere deformity in both the proximal turndown and
      graft group.

PMID- 24873097
TI  - Successful NBCA embolization of a T2 aneurysmal bone cyst.
AB  - Surgically accessible aneurysmal bone cysts (ABC) have traditionally been treated
      with curettage. Selective arterial embolization was initially proposed as a
      preoperative adjuvant to reduce peroperative bleeding. Currently, the role of
      embolization has been extended to the definitive treatment of aneurysmal bone
      cyst of the spine in children, as well as to other locations in the skeleton. The
      authors describe the technique in a 15-year-old girl with a T2 aneurysmal bone
      cyst. Digital subtraction angiography was performed for tumor vascular mapping,
      followed by selective arterial embolization with N-butyl 2 cyanoacrylate (NBCA).
      Because of persistent local pain, repeat embolization was done at 8 months. Pain
      relief and progressive ossification of the lesion were now observed. At 4-year
      follow-up, the patient was asymptomatic, with complete ossification of the
      lesion. Selective arterial embolization (SAE) is a minimally invasive, safe and
      effective procedure for the permanent occlusion of the pathological feeding
      vessels of spinal ABC. It should be considered as the treatment of choice for
      lesions difficult to access with surgery, especially in young patients. Careful
      pre-embolization vascular mapping of the lesion, operator's experience and use of
      NBCA are the keys to success.

PMID- 24873098
TI  - Three-dimensional virtual reality simulation of periarticular tumors using
      Dextroscope reconstruction and simulated surgery: a preliminary 10 case study.
AB  - Dextroscope three-dimensional (3D) imaging has been extensively applied for
      generation of virtual reality (VR) workspaces for in neurosurgery and
      laparoscopy, though few applications in orthopedic surgery have been reported.
      Patients undergoing surgery for periarticular tumors (n = 10) from Oct. 2008 to
      Jun. 2010 were enrolled and presurgically subjected to computed tomography (CT),
      magnetic resonance imaging (MRI), and MRI angiography (MRI-A). Imaging data was
      transferred and integrated in Dextroscope, producing a VR simulation. Resultant
      presurgical 3D anatomical reconstructions and intraoperative anatomical
      characteristics (virtual vs. actual data) and surgical approach (virtual vs.
      actual situation) measurement and subjective appearance were compared. Anatomical
      characteristics in the area of interest and tumor diameters were consistent
      between virtual and actual data. However, the virtual surgical situations
      remained inconsistent with the actual intraoperative situation in many cases,
      leading to complications. The resolution of original CT, MRI, and MRI-A images
      directly correlated with the quality of 3D simulations, with soft tissues most
      poorly represented. Tumor tissue imaging quality in 3D varied extensively by
      tumor type. CONCLUSIONS: Anatomical structures of periarticular tumors can be
      reconstructed using the Dextroscope system with good accuracy in the case of
      simple fenestration, increasing individualization of treatment, surgical
      competence level, and potentially reducing intraoperative complications. However,
      further specialization of VR tools for use in orthopedic applications that
      involve specialized tools and procedures, such as drilling and implant placement,
      are urgently required.

PMID- 24873099
TI  - Solitary bone metastases of unknown origin.
AB  - Patients with a newly detected solitary bone metastasis and no history of cancer
      need extensive diagnostic testing. One hundred and twenty biopsy samples of
      patients with metastatic bone disease were referred to the authors' pathology
      department between June 2005 and December 2012. Thirty-three (27.5%) of these
      patients with a solitary metastasis of unknown origin, and without visceral
      metastases, were studied retrospectively. Most metastases were found in the spine
      (14/33 or 42.4%), or in the pelvis (7/33 or 21.2%). The lung was the most common
      primary site, but this is not universal in the literature. A useful flowchart for
      the clinician, confronted with a bone metastasis from an unknown primary site, is
      the following, according to the literature: history and physical examination,
      biochemistry with tumor markers and immunoelectrophoresis, chest radiograph, CT
      scan of chest and abdomen, and bone scan.

PMID- 24873100
TI  - Intramedullary nailing without curettage and cement augmentation for the
      treatment of impending and complete pathological fractures of the proximal or
      midshaft femur.
AB  - Metastases in the proximal femur and in the femoral diaphysis are usually treated
      with either cephalomedullary or intramedullary nailing. The benefit of curettage
      and augmentation of the nail with methyl methacrylate remains controversial. The
      authors retrospectively studied the outcomes with cephalomedullary and
      intramedullary nailing without curettage and methyl-methacrylate augmentation for
      lytic metastases of the proximal/diaphyseal femur. Twenty-one complete (11) or
      impending (10) pathological fractures in 19 consecutive patients were treated
      between January 2006 and August 2013. There were 11 women and 8 men. Their mean
      age was 62 years (range, 38 to 87). All patients received adjuvant chemotherapy
      or radiotherapy.The average postsurgical survival was 9.7 months (range 1-36
      months). A single deep infection was debrided. Seventeen out of 19 patients were
      ambulatory, with or without a walking aid. No implant failure was noted. In other
      words, patients succumbed to the disease prior to hardware failure. Femoral nail
      insertion without curettage and cement augmentation provided satisfactory
      stabilization of proximal and diaphyseal femur fractures, impending or complete,
      even when there was massive bone destruction.

PMID- 24873101
TI  - "The appetite for pay protests appears strong".

PMID- 24873102
TI  - 6Cs to apply to all NHS workers.

PMID- 24873103
TI  - "Entertaining, interactive games can improve staff engagement".

PMID- 24873104
TI  - "Expert patients cannot do it all--they still need expert care".

PMID- 24873105
TI  - What to do if you are referred to the NMC.
AB  - If you are subject to an investigation by a professional regulator, you need to
      be informed about the process and act quickly. This article outlines the process
      and offers some advice on how best to navigate it.

PMID- 24873106
TI  - Patient and family views of nutritional status.
AB  - Providing adequate food in hospitals remains a concern for those involved in
      healthcare as well as patients and relatives. We conducted a small-scale survey
      to explore relatives' and patients' perceptions about the risk of developing
      malnutrition in hospital and to gauge whether further more in-depth audit was
      required.

PMID- 24873108
TI  - Who provides end-of-life care in care homes?

PMID- 24873107
TI  - Continence advice by telehealth for young people.
AB  - Children and young people operate in an advanced technological world where new,
      exciting opportunities exist for remote interactions. To engage with these
      service users, we set up a nurse-led telehealth facility that enabled young
      people with spina bifida to access specialist continence service from home. This
      article describes efforts to embed this innovation into practice and offer
      insight to some of the challenges we faced in the process. It offers practical
      guidance on setting up similar services.

PMID- 24873109
TI  - Ban the advertising of formula.

PMID- 24873110
TI  - 'Pressure points' survey highlights failings in postnatal care.

PMID- 24873111
TI  - Use of acupuncture during labour.
AB  - Acupuncture is becoming widely recognised as an effective method of pain relief
      and is being increasingly integrated within the NHS, particularly for the
      treatment of tension-type headache, migraine and low back pain. Acupuncture
      during labour has been shown by a Cochrane review to reduce labour pain
      intensity, increase patient satisfaction and limit the use of pharmacological
      analgesia (Smith et al 2011) and epidural anaesthesia (Nesheim and Kinge 2006).
      It may therefore be particularly suited to labouring women who wish to avoid more
      invasive forms of pain relief. Furthermore, women receiving acupuncture in labour
      appear to experience additional benefits including shorter labours and reduced
      rates of instrumental vaginal birth (Smith et al 2011). In the UK, intrapartum
      acupuncture is usually provided by professional acupuncturists, but in countries
      such as Germany and Scandinavia it is widely given by midwives. A midwife
      delivered acupuncture service appears to be a similarly feasible and cost
      effective option in the UK and is currently being piloted at University College
      London Hospitals NHS Trust.

PMID- 24873112
TI  - Benefits of infant massage.
AB  - After spending three months as a clinical midwifery tutor at a remote hospital in
      Zambia, where I helped to train student midwives and other students, my interest
      in infant massage was ignited, having witnessed the benefits of massage to both
      mother and baby. Once back in the UK, I trained and qualified as a massage
      instructor with an international infant massage training organisation, which has
      led me to work extensively with parents and babies, offering one-to-one and group
      courses. It has been a privilege to be able to teach parents the valuable skill
      of infant massage, and consequently pass on the benefits both physiological and
      psychosocial.

PMID- 24873113
TI  - Hypnotherapy for birth.
AB  - There are many misunderstandings about hypnotherapy for birth and how best to
      support a woman who has chosen to use it. This article brings together
      experiences of midwives who have attended women in labour using hypnotherapy, and
      aims to help birth professionals understand a bit more about hypnotherapy and how
      they can best support women who are using it. It is a personal account from a
      hypnotherapy trainer reflecting on her encounters with midwives as they share
      experiences of observing hypnotherapy in action.

PMID- 24873114
TI  - The multisensory approach to birth and aromatherapy.
AB  - The birth environment continues to be a subject of midwifery discourse within
      theory and practice. This article discusses the birth environment from the
      perspective of understanding the aromas and aromatherapy for the benefit of women
      and midwives The dynamic between the olfactory system and stimulation of normal
      birth processes proves to be fascinating. By examining other health models of
      care we can incorporate simple but powerful methods that can shape clinical
      outcomes. There is still more that midwives can do by using aromatherapy in the
      context of a multisensory approach to make birth environments synchronise with
      women's potential to birth in a positive way.

PMID- 24873115
TI  - The role of yoga: breathing, meditation and optimal fetal positioning.
AB  - Yoga is considered a good form of exercise in pregnancy (NHS Choices recommend
      exercise such as yoga, amongst others) to help women keep fit during their
      pregnancy and prepare for the birth. But apart from the physical postures, yoga
      has plenty to offer. The breathing and meditation techniques keep pregnant
      mothers healthy and relaxed, and provide the mental focus to aid childbirth. In
      this article we look at yogic breathing and meditation techniques for midwives to
      recommend to expectant mothers, and some postures that specifically help to
      encourage an optimal fetal position.

PMID- 24873116
TI  - Hay fever in pregnancy.
AB  - Spring and summer can bring misery to millions who suffer from allergic reactions
      to pollen. Hay fever can cause runny noses, streaming eyes and sore throats.
      Sadly, many treatments for this distressing condition are not recommended during
      pregnancy because of fears surrounding the effect on the unborn child. This
      article presents the causes and treatments of hay fever and explores the
      alternatives for use during pregnancy which may be able to relieve or minimise
      the unpleasant symptoms without harming the baby.

PMID- 24873118
TI  - The national infant feeding network.

PMID- 24873117
TI  - Osteopathy: helping pregnant women in pain.
AB  - Various therapies are accessed by women who are looking to enhance the experience
      of pregnancy or to relieve pain from pregnancy-related ailments. This article
      gives an introduction to how osteopathy may help women presenting with pain. It
      includes an overview of a case study, in order that midwives can gain insight
      into how osteopathic medicine approaches and applies knowledge of anatomy and
      physiology to improve biomechanics that may have become sub optimal giving the
      symptom of pain. An underlying philosophy of structure governs function.

PMID- 24873119
TI  - Back to the future.

PMID- 24873120
TI  - The upcoming political season puts pressure on Obamacare support.

PMID- 24873121
TI  - Eleven essential steps to purchasing or selling a medical practice.
AB  - Based on our experience in representing more than 100 doctors and medical
      specialists in practice sales and acquisitions, we have identified 11 key
      considerations important to a deal. There are several issues to consider while
      going through the process of buying or selling a practice including the
      implementation of a "letter of intent" as a first step rather than drafting a
      contract, securing a lease, and verifying the property is not in violation of the
      local zoning requirements. There are also considerations with regard to the
      patients, which range from how will the accounts receivable at the time of the
      closing be handled to who is responsible for the handling of continued treatment
      in an ongoing case after a deal is finalized. This article details these
      considerations and more.

PMID- 24873122
TI  - Using patient safety organizations to further clinical integration.
AB  - This article addresses why in the current context of driving toward improved
      value, physician groups ought to consider developing a patient safety evaluation
      system and reporting to a patient safety organization. The fundamental challenge
      to physicians to succeed in the future is to clinically integrate within their
      own practices, standardizing to the evidence base, and measuring their
      performance. In addition, it is increasingly clear that the physician office
      practice is a source of patient safety issues. The Patient Safety and Quality
      Improvement Act provides two powerful protections for data that will support and
      bolster clinical integration and patient safety. The protections and how to
      deploy them are presented.

PMID- 24873123
TI  - How geographical information systems analysis influences the continuum of patient
      care.
AB  - As the vast repository of data about millions of patients grows, the analysis of
      this information is changing the provider-patient relationship and influencing
      the continuum of care for broad swaths of the population. At the same time, while
      population health management moves from a volume-based model to a value-based one
      and additional patients seek care due to healthcare reform, hospitals and
      healthcare networks are evaluating their business models and searching for new
      revenue streams. Utilizing geographical information systems to model and analyze
      large amounts of data is helping organizations better understand the
      characteristics of their patient population, demographic and socioeconomic
      trends, and shifts in the utilization of healthcare. In turn, organizations can
      more effectively conduct service line planning, strategic business plans, market
      growth strategies, and human resource planning. Healthcare organizations that use
      GIS modeling can set themselves apart by making more informed and objective
      business strategy decisions.

PMID- 24873124
TI  - Challenges and opportunities facing physicians in 2014.

PMID- 24873125
TI  - Comply with regulations or risk paying hefty fines: ten tips for choosing call
      recording to help ensure compliance.
AB  - Medical practices are paying hundreds of thousands of dollars in fines for not
      complying with various governmental regulations, including a variety of HIPAA
      rules and credit card compliance. One solution to help reduce this risk and avoid
      fines is to use call recording to help ensure compliance. This article provides
      readers with key considerations for choosing and implementing a call recording
      solution for their medical practices to ensure that it will be compliant with key
      regulations. These tips include being able to customize call recording policies
      and procedures for their unique needs; providing secure, private storage;
      allowing easy access for authorized users; secure sharing of call recordings;
      regulatory compliance training; disaster recovery; and maintaining an audit-ready
      and compliant-evident state at all times.

PMID- 24873126
TI  - A field guide to real-time culture change: just "rolling out" a training program
      won't cut it.
AB  - Presented as a representative case of how to handle the disruptive behaviors of
      professionals in healthcare, this article describes the strategies of a systems
      approach with a five-phase model for culture change. The "large-scale, real-time"
      culture change process, based on our own evidence-based research on toxic
      behaviors and the research of others, has been demonstrated to be more effective
      than one-on-one feedback to change these behaviors. The real-time approach has
      been applied to other organizational situations--strategy formulation, change
      management, or service improvement--with more sustainable effects than simply
      training alone. This article will help your organization with four outcomes:
      understanding the rationale for a five-phase model for cultural change,
      describing the advantages of a real-time versus nonreal-time approach to change,
      identifying the how-to's for application within a systems approach, and
      articulating a clear evaluation process to sustain successful organizational
      culture change.

PMID- 24873127
TI  - Impaired physicians.
AB  - Nearly every physician has encountered a doctor who is causing problems in the
      practice or at the hospital. These include physicians who are impaired because of
      drug or alcohol abuse. Managing these physicians and helping them get back on
      track can be difficult and daunting. This article will discuss impaired
      physicians with suggestions for interacting with them and helping them become
      valuable members of the team.

PMID- 24873128
TI  - Physician-administrator teams.

PMID- 24873129
TI  - Liability of physicians supervising nonphysician clinicians.
AB  - Physicians confront a variety of liability issues when supervising nonphysician
      clinicians (NPC) including: (1) direct liability resulting from a failure to meet
      the state-defined standards of supervision/collaboration with NPCs; (2) vicarious
      liability, arising from agency law, where physicians are held accountable for NPC
      clinical care that does not meet the national standard of care; and (3)
      responsibility for medical errors when the NPC and physician are co-employees of
      the corporate enterprise. Physician-NPC co-employee relationships are highlighted
      because they are new and becoming predominant in existing healthcare models.
      Because of their novelty, there is a paucity of judicial decisions determining
      liability for NPC errors in this setting. Knowledge of the existence of these
      risks will allow physicians to make informed decisions on what relationships they
      will enter with NPCs and how these relationships will be structured and
      monitored.

PMID- 24873130
TI  - It's time to rebrand progressive discipline to structured achievements.
AB  - The concept of progressive discipline has traditionally been communicated as a
      common way to address performance issues in the U. S. workforce. In practice,
      progressive discipline is all too often implemented as a negative, demoralizing
      process that leads--or is threatened to lead--to the termination of employment.
      This article challenges a change in the way progressive discipline is managed and
      communicated from a negative, threatening perspective to one that involves a
      series of structured achievements that are effective in helping employees meet or
      exceed the requirements of the job.

PMID- 24873131
TI  - Caveats for doctors providing care for themselves, family, friends, and
      colleagues.
AB  - Physicians are almost always asked by a family member, friend, other healthcare
      provider, or an employee to provide him or her with medical care. Often this
      request for medical care is made over the phone, at a social gathering, or in the
      hallway of hospital. This article will discuss the ethics involved with providing
      medical care to family, friends, and colleagues and suggest guidelines for caring
      for these special people/patients.

PMID- 24873132
TI  - Managing the culturally diverse medical practice team: twenty-five strategies.
AB  - A common misconception is that the phrase workplace diversity means meeting
      certain quotas in employee race or gender categories. In fact, diversity is much
      more than that. This article explores the unique benefits and challenges of
      managing a culturally diverse medical practice team and offers practice managers
      25 practical strategies. It describes the two types of diversity training that
      are beneficial to practice managers and the kinds of policies, practices, and
      procedures that foster and promote diversity. This article also explores
      ethnocentrism, racism, ageism, sexism, stereotyping, and other potentially
      divisive issues among a diverse medical practice team. It provides an assessment
      instrument practice managers can use to evaluate their own diversity management
      skills. Finally, this article defines specifically what is meant by the term
      diversity and explores the top 10 diversity issues in workplaces today.

PMID- 24873133
TI  - Leveraging business intelligence to make better decisions: Part I.
AB  - Data is the new currency. Business intelligence tools will provide better
      performing practices with a competitive intelligence advantage that will separate
      the high performers from the rest of the pack. Given the investments of time and
      money into our data systems, practice leaders must work to take every advantage
      and look at the datasets as a potential goldmine of business intelligence
      decision tools. A fresh look at decision tools created from practice data will
      create efficiencies and improve effectiveness for end-users and managers.

PMID- 24873134
TI  - The Patient-Centered Medical Home and Meaningful Use: a challenge for better
      care.
AB  - This article discusses and illustrates the alignment between the National
      Committee for Quality Assurance's Patient-Centered Medical Home and Meaningful
      Use. In addition to the various overlaps, there is also significant discussion
      about Patient-Centered Medical Home and Meaningful Use as well as their distinct
      requirements. With impending deadlines for Meaningful Use and potential penalties
      being imposed, this article provides a layout of dates, stages, and incentive
      payments and penalties for Meaningful Use, and discusses how obtaining Patient
      Centered Medical Home recognition could be beneficial to achieving Meaningful
      Use.

PMID- 24873135
TI  - Updates on safe harbor 401(K) plans, healthcare exchanges, cafeteria plans, and
      retirement plan contribution limits.

PMID- 24873137
TI  - [The brain histamine H3 receptors: sleep-wake control and novel therapeutic
      targets for sleep disorders].
AB  - Histaminergic neurons are located exclusively in the posterior hypothalamus from
      where they project to virtually all brain areas and fulfill a major role in the
      maintenance of waking. H3-receptors are firstly autoreceptors damping the release
      and synthesis of histamine and the firing of histamine neurons. This action also
      extends to heteroreceptors on most other neurotransmitter systems, allowing a
      powerful control over multiple homeostatic functions. The particular properties
      and locations of H3-receptors provide quite favorable attributes to make this a
      most promising target for sleep-wake control and sleep disorders. This review
      summarizes the most recent data on the role of H3-receptor in physiological sleep
      wake regulation and preclinical and clinical evidence supporting H3-receptor as
      brain target for therapy of sleep and vigilance disorders.

PMID- 24873136
TI  - [Recent progress in the development of atherosclerosis: role of heat shock
      protein].
AB  - Recent studies have shown a close relationship between heat shock proteins (HSPs)
      and atherosclerosis. HSP60 may promote the development of atherosclerosis by
      inducing autoimmune response, enhancing inflammatory response, promoting
      proliferation and migration of vascular smooth muscle cells. While HSP27 may
      protect the blood vessels from oxidative stress, reduce inflammatory response,
      inhibit proliferation, migration and apoptosis of vascular smooth muscle cells,
      and stabilize the atherosclerotic plaque. These new understanding of the role of
      HSPs provides useful clues for the diagnosis and treatment of atherosclerosis.

PMID- 24873138
TI  - [Lipoprotein lipase and diabetic cardiomyopathy].
AB  - Lipoprotein lipase (LPL) hydrolyzes plasma triglyceride-rich lipoproteins into
      free fatty acids (FFA) to provide energy for cardiac tissue. During diabetes,
      cardiac energy supply is insufficient due to defected utilization of glucose. As
      a compensation of cardiac energy supply, FFAs are released through the hydrolysis
      of very low density lipoprotein (VLDL) and chylomicrons (CM) due to activation of
      LPL activity. In diabetic patients, activated LPL activity and elevated FFAs
      result in the intracellular accumulation of reactive oxygen species and lipids in
      myocardium and potentially induce the diabetic cardiomyopathy (DCM). The present
      review summarizes the regulatory mechanisms of myocardial LPL and the
      pathogenesis of DCM induced by LPL and provides novel therapeutic targets and
      pathways for DCM.

PMID- 24873139
TI  - [The mechanisms of high-phosphate-induced vascular calcification in patients with
      chronic kidney disease].
AB  - Vascular calcification is the leading cause of cardiovascular diseases in chronic
      kidney disease (CKD) patients. Hyperphosphatemia is common in CKD patients,
      mainly because of dysfunction of kidney and dysregulation of hormones. Many
      studies indicate that elevated plasma phosphate level has direct effects on
      vascular smooth muscle cells (VSMCs) and drives calcification. Recent findings
      suggest that elevated phosphate can induce chondrogenic/osteogenic
      differentiation of VSMCs, promote VSMC apoptosis and activate oxidative stress
      and inflammation, all of which contribute to vascular calcification. In this
      review, we highlight the advances in the mechanisms of vascular calcification
      caused by elevated phosphate and the preventing effects of phosphate control
      therapy on vascular calcification.

PMID- 24873141
TI  - [Recent progress of Ca2+/calmodulin-dependent protein kinase II in cardiovascular
      diseases].

PMID- 24873140
TI  - [The function of 17beta-hydroxysteroid dehydrogenase family].

PMID- 24873142
TI  - [Research progress in the function and signaling pathways of immunoglobulin D and
      its receptor].

PMID- 24873143
TI  - [Research progress of argininosuccinate synthase].

PMID- 24873145
TI  - [Correlation between lymphangiogenesis and lymphatic metastasis in breast
      cancer].

PMID- 24873144
TI  - [Mechanism of apoptin-induced apoptosis and the application in cancer therapy].

PMID- 24873147
TI  - [Microbial quorum sensing signals and the host immuno-regulation].

PMID- 24873146
TI  - [Advances in the studies of FoxO1 and diabetes].

PMID- 24873148
TI  - [Contribution of selective insulin resistance to the dysfunction of the vascular
      endothelium].

PMID- 24873149
TI  - [NF- kappaB signal pathway and inflammation].

PMID- 24873150
TI  - [Endoplasmic reticulum stress and vascular endothelial injury in type 2 diabetes
      mellitus].

PMID- 24873151
TI  - [A founder of molecular biology who proposes the operon model: Francois Jacob].

PMID- 24873152
TI  - [Clinical studies of shang ring male circumcision in China and Africa].
AB  - HIV/STIs remain a major global public health problem. One of the global
      strategies for the prevention and control of HIV/STIs is to interrupt their
      transmission, which requires the public health methods based on scientific
      evidence and cost-effectiveness. The scale-up of male circumcision services in
      the priority countries of the HIV-prevention project in sub-Saharan Africa has
      been hampered by the scarcity of trained providers and relative technical
      difficulty of male circumcision techniques recommended by WHO and UNAIDS. Shang
      Ring is an innovative and disposable device for male circumcision, which has been
      safely used for over 600 000 males in China since 2006. Clinical studies of more
      than 3 000 cases of Shang Ring circumcision in China, Kenya, Zambia, and Uganda
      have demonstrated its safety, effectiveness, acceptability and ease of use. The
      most obvious advantages of Shang Ring include short procedure time (3-6 min),
      excellent postoperative cosmesis, low rate of complications, high acceptance by
      clients and providers, ease of use, and standardization for reliable performance.
      As an innovative technique, Shang Ring has a great potential for facilitating the
      safe and effective scale-up of circumcision services. This article
      comprehensively reviews the clinical studies of Shang Ring male circumcision in
      China and Africa.

PMID- 24873153
TI  - [Expressions of CSE and CBS in the penile corpus cavernosum of hyperglycemia rats
      and their implications].
AB  - OBJECTIVE: To investigate the impact of hyperglycemia on the hydrogen sulfide
      (H2S) signaling pathway in rat penile tissue and its relationship with erectile
      function. METHODS: Twenty healthy male Sprague Dawley (SD) rats aged 8 weeks were
      randomly divided into groups A (4-week healthy control), B (4-week diabetes
      mellitus model), C (6-week healthy control) and D (6-week diabetes mellitus
      model). The rats in groups B and D were injected intraperitoneally with
      streptozotocin at 50 mg/kg to induce diabetes mellitus, while those in groups A
      and C with the same volume of normal saline. The animals were killed at 4 (groups
      A and B) and 6 weeks (groups C and D) after treatment for measurement of the
      maximal intracavernous pressure/mean arterial blood pressure (ICP(max)/MAP) by
      electrostimulation, determination of the H2S concentration in the plasma and
      penile tissue, and detection of the expressions of cystathionine-beta-synthetase
      (CBS) and cystathionine-gamma-lyase (CSE) in the penile corpus cavernosum by
      immunohisto- chemistry and Western blot. RESULTS: With electrostimulation of the
      pelvic ganglia at 5V and 7 V, ICP(max)/MAP was significantly reduced in groups B
      (0.19 +/- 0.03 and 0.29 +/- 0.04) and D (0.14 +/- 0.04 and 0.25 +/- 0.04) as
      compared with A (0.46 +/- 0.07 and 0.68 +/- 0.09) and C (0.43 +/- 0.07 and 0.65
      +/- 0.16) (P < 0.05). No statistically significant differences were found in the
      level of serum testosterone either between groups A and B ([469.19 +/- 126.46]
      ng/dl vs [359.08 +/- 60.06] ng/dl, P > 0.05) or between C and D ([470.44 +/-
      209.28] ng/dl vs [297.01 +/- 96.58] ng/dl, P > 0.05). Groups B and D showed
      remarkable reduction in the H2S concentration (P < 0.05) and the expressions of
      CBS and CSE (P < 0.05) in comparison with A and C, and the CBS and CSE
      expressions were even more significantly decreased in D than in B (P < 0.05).
      CONCLUSION: The reduced concentration of H2S and decreased expressions of CBS and
      CSE in the penile corpus cavernosum of the diabetic rats suggested that the H2S
      signaling pathway might be involved in hyperglycemia-induced erectile
      dysfunction.

PMID- 24873154
TI  - [Lipopolysaccharide affects testicular histology and reproductive endocrine
      function in male rats].
AB  - OBJECTIVE: To study the influence of lipopolysaccharide (LPS)-induced
      inflammation on the testicular histology and reproductive endocrine function in
      male rats and investigate the possible mechanism of inflammation affecting male
      fertility. METHODS: Thirty-six male SD rats were randomly divided into a control
      group (A) and three LPS intervention groups (B, C, and D) to receive saline and
      LPS (5 mg/kg i. p, once), respectively. The animals in groups B, C, and D were
      killed by anesthesia at 12, 24, and 72 hours after treatment. Histopathological
      changes in the left testis of the rats were observed by HE staining and the
      levels of the reproductive hormones T, FSH, and LH in the serum were determined
      by ELISA. RESULTS: Compared with group B, group A showed clear structure of
      seminiferous tubules, orderly arrangement of spermatogenic cells, a slightly
      decreased number of sperm in some seminiferous tubular lumens, and shed
      spermatogenic cells in the rat testis tissue; group C exhibited thinner
      seminiferous epithelia, disordered structure of seminiferous tubules, irregular
      arrangement of spermatogenic cells, decreased number of mature sperm and obvious
      shedding of spermatogenic cells in seminiferous tubular lumens; group D
      manifested similar findings to those of group C, with even more shed
      spermatogenic cells that blocked the tubular lumens. The levels of serum T, LH,
      and FSH were (0.490 +/- 0.028) ng/ml, (6.290 +/- 0.515) ng/L, and (1.837 +/-
      0.127) IU/L in group A, (0.460 +/- 0.024) ng/ml, (5.881 +/- 0.124) ng/L, and
      (1.707 +/- 0.098) IU/L in group B, (0.417 +/- 0.021) ng/ml, (5.123 +/- 0.271)
      ng/L, and (1.620 +/- 0.115) IU/L in group C, and (0.378 +/- 0.021) ng/ml, (4.504
      +/- 0.279) ng/L and (1.562 +/- 0.216) IU/L in group D, all decreased in group B
      as compared with A (P > 0.05). The decreases of T and LH were extremely
      significant (P < 0.01) and that of FSH was significant in groups C and D (P <
      0.05) in comparison with A. CONCLUSION: LPS-induced inflammation affects the
      testicular tissue and reproductive endocrine function of male rats, resulting in
      decreased levels of serum T, LH, and FSH.

PMID- 24873155
TI  - [Inhibitory effect of salidroside on hypoxia-induced apoptosis of corpus
      cavernosum smooth muscle cells in rats].
AB  - OBJECTIVE: To investigate the effect of salidroside on hypoxia-induced apoptosis
      of corpus cavernosum smooth muscle cells (CCSMCs) in rats. METHODS: Rat CCSMCs
      were cultured in vitro by the enzyme digestion method and identified by
      immunofluorescent staining of anti-alpha-SMA and anti-Desmin. The non-toxic dose
      of salidroside was determined by MTT assay. Low-oxygen mixed gas (1% O2, 5% CO2,
      and 94% N2) was piped into a modular incubator chamber to induce hypoxia. The
      CCSMCs were divided into a normal, a hypoxia, and a 32 microg/mL salidroside
      intervention group. The apoptosis of the CCSMCs was detected by flow cytometry
      and the expression of the caspase-3 protein determined by Western blot. RESULTS:
      The majority of the CCSMCs were positive for alpha-SMA and Desmin at
      immunofluorescent staining. Salidroside at < 32 microg/ml produced no obvious
      toxicity to CCSMCs. Compared with the normal control group, the rates of early
      and late apoptosis of CCSMCs were both increased significantly in the hypoxia
      group ([12.77 +/-1.41]% vs [18.69 +/- 1.29]%, P < 0.01 and [14.63 +/- 2.00]% vs
      [21.03 +/- 1.530]% , P < 0.05). Western blot showed a markedly increased
      expression of cleaved caspase-3 (P < 0.01). Intervention with 32 microg/ml
      salidroside significantly reduced hypoxia-induced early apoptosis of CCSMCs
      ([13.46% +/- 1.87]%, P < 0.01) and decreased the expression of cleaved caspase-3
      (P < 0.01). CONCLUSION: Salidroside can reduce the expression of cleaved caspase
      3 and inhibit hypoxia-induced apoptosis of CCSMCs in rats.

PMID- 24873156
TI  - [Roles of adenosine and cytokines in the prostate tissue of rats with acute
      bacterial prostatitis].
AB  - OBJECTIVE: To investigate the possible roles of adenosine and the cytokines TNF
      alpha and IL-10 in the pathogenesis of acute bacterial prostatitis (ABP) in rats.
      METHODS: Forty-eight male Wistar rats were randomly divided into groups A (ABP),
      B (ABP + theophylline intervention), C (sham) and D (blank control). ABP models
      were established by injecting Escherichia coli 0157 into the prostate, and those
      in group B were treated by intraperitoneal injection of theophylline immediately
      after modeling. At 4 and 14 days, the prostate tissues of the rats were collected
      for detection of the expressions of TNF-alpha and IL-10 by immunohistochemistry
      and the concentration of adenosine by high-performance liquid chromatography.
      RESULTS: At 4 and 14 days, the concentrations of adenosine were significantly
      higher in group A ([48.38 +/- 17.27] and [26.54 +/- 11.22] microg/g) than in C
      ([0.45 +/- 0.25] and [0.46 +/- 0.29] microg/g) and D ([0.41 +/- 0.23] and [0.43
      +/- 0.27] microg/g) (P < 0.05), and so were the expressions of TNF-alpha in A
      (0.23 +/- 0.08 and 0.21 +/- 0.03) than in C (0.07 +/- 0.03 and 0.07 +/- 0.01) and
      D (0.07 +/- 0.06 and 0.07 +/- 0.06) (P < 0.05), and those of IL-10 in A (0.13 +/-
      0.03 and 0.25 +/- 0.01) than in C (0.07 +/- 0.03 and 0.07 +/- 0.03) and D (0.07
      +/- 0.01 and 0.07 +/- 0.02) (P < 0.05). Compared with group A, the rats in group
      B showed significant increases at 4 and 14 days in the severity of inflammation,
      concentration of adenosine ([86.64 +/- 32.87] and [51.17 +/- 22.96] microg/g, P <
      0.05) and expression of TNF-alpha (0.37 +/- 0.08 and 0.32 +/- 0.06, P < 0.05),
      but exhibited no remarkable difference in the expression of IL-10 (0.12 +/- 0.06
      and 0.15 +/- 0.06, P > 0.05). CONCLUSION: Adenosine may affect the progression of
      inflammation by regulating the expressions of the cytokines TNF-alpha and IL-10
      in ABP rats through the adenosine receptor signaling pathway.

PMID- 24873157
TI  - [Circumcision with no-flip Shang Ring technique for adult males: analysis of 168
      cases].
AB  - OBJECTIVE: To observe the clinical effects of the no-flip procedure with the
      Chinese Shang Ring when circumcising adult males with redundant prepuce or
      phimosis, and to discuss its advantages and disadvantages. METHODS: Using the no
      flip Shang Ring technique, we performed circumcision for 167 adult males aged 18 
      72 (mean 27.8) years with redundant prepuce or phimosis, and analyzed the
      clinical data, including the operation time, postoperative complications, ring
      removal time, and postoperative appearance of the penis. RESULTS: Complete follow
      up data of 94 cases (56.29%) were obtained. The mean operation time was (5.03 +/-
      0.71) minutes and the average ring-removal time was (18.83 +/- 6.70) days. The
      primary postoperative complications were edema (35 cases [37.23%] at 2 weeks and
      9 cases [9.57%] at 4 weeks), including 2 severe cases (2.13%), and infection (3
      cases [3.19%]). The pain scores were 2.01 +/- 2.46 during the procedure and 4.52
      +/- 2.53 at 24 hours postoperatively. Slipping of the outer ring occurred in 1
      case, and delayed removal of the ring in 30 cases (31.91%). CONCLUSION: Adult
      male circumcision with the no-flip Shang Ring technique is recommended for its
      short operation time, simple procedure, fewer postoperative complications, less
      pain, and better incision appearance.

PMID- 24873158
TI  - [Outward versus inward placement in Shang Ring circumcision for phimosis and
      redundant prepuce in adult men: analysis of 527 cases].
AB  - OBJECTIVE: To observe the clinical effects of two different circumcision
      procedures with the Shang Ring and compare their advantages and disadvantages.
      METHODS: A total of 527 adult males with phimosis or redundant prepuce underwent
      Shang Ring circumcision by conventional outward replacement (n = 254) and inward
      placement (n = 273), respectively. We observed the in-ring nocturnal pain,
      complications, ring-removal pain, degree of edema, recovery time, and patients'
      satisfaction after surgery, and compared them between the two groups. RESULTS:
      Compared with the conventional outward placement (5.9%) of the Shang Ring, the
      inward placement method showed the advantages of mild in-ring nocturnal pain, a
      low complication rate, significantly reduced ring-removal pain, and mild edema,
      but exhibited longer healing time. CONCLUSION: In Shang Ring circumcision for
      phimosis and redundant prepuce in adult males, each of the outward and inward
      placement methods has advantages and disadvantages of its own, but the latter is
      more advantageous and feasible.

PMID- 24873159
TI  - [Shang Ring circumcision by transverse incision in the distal penis foreskin and
      pull-up of the interior board for short frenulum praeputii].
AB  - OBJECTIVE: To investigate the effectiveness of surgical strategies for Shang Ring
      circumcision in the treatment of short frenulum praeputii in patients with
      redundant prepuce or phimosis. METHODS: Totally, 130 cases of short frenulum
      praeputii with redundant prepuce or phimosis were randomly assigned to an
      experimental group and a control group of equal number to receive Shang Ring
      circumcision, the former by transverse incision in the distal penis foreskin and
      pull-up of the interior board, and the latter by conventional transverse incision
      and longitudinal suture of the frenulum praeputii. Comparisons were made between
      the two groups in the surgical duration, intraoperative blood loss, 24 h
      postoperative pain visual analog score (VAS), postoperative complications,
      satisfaction with the penile appearance, and the quality of sexual life. RESULTS:
      The surgical duration, intraoperative blood loss, 24 h postoperative VAS,
      postoperative sexual satisfaction, and satisfaction with penile appearance were
      (4.60 +/- 1.20) min, (2.61 +/- 1.81) ml, 1.73 +/- 0.76, 98.5%, and 98.5%,
      respectively, in the experimental group, as compared with (21.60 +/- 6.30) min,
      (11.10 +/- 3.40) ml, 5.37 +/- 1.84, 70.3% and 69.8% in the control, with
      statistically significant differences between the two groups (P < 0.05). The
      incidence rates of such major complications as wound dehiscence, infection, and
      moderate to severe edema were 1.5% (1/65), 3.1% (2/65), and 4.6% (3/65),
      respectively, in the experimental group in comparison with 12.3% (8/65), 15.3%
      (10/65), and 30.7% (20/65) in the control, with statistically significant
      differences between the two groups (P < 0.05). None of patients had any serious
      complications. CONCLUSION: Shang Ring circumcision by transverse incision in the
      distal penis foreskin and pull-up of the interior board, with its advantages of
      shorter operation time, less blood loss, mild pain, fewer complications, and
      higher satisfaction and acceptance of the patients, can be used as an safe and
      effective approach to the treatment of short frenulum praeputii.

PMID- 24873160
TI  - [Semen expulsion under the ureterocystoscope].
AB  - OBJECTIVE: To determine the exact location of the opening of the ejaculatory duct
      in men and provide some basic anatomical evidence for seminal vesiculoscopy and
      the treatment of ejaculatory duct obstruction. METHODS: We performed
      ureterocystoscopy for 21 male patients aged 26 - 47 years with hematuria (n =
      12), hematospermia (n = 2), glandular cystitis (n = 6), and anejaculation after
      radical resection of rectal carcinoma (n = 1), and meanwhile, with the consent of
      the patients, massaged the prostate and ejaculatory duct and observed the outlet
      of the expelled fluid. Under the microscope, we described the fluid samples with
      sperm as the expulsion from the ejaculatory duct. RESULTS: Ureterocystoscopy
      showed that the exact anatomical sites of the expulsion of prostatic fluid and
      semen in the patients were the side and lower side of the prostatic utricle
      opening above the verumontanum and the ventral side of the verumontanum.
      Quantities of sperm were found in the expulsion fluid of 13 of the patients, and
      no expulsion, including semen, was seen from the prostatic utricle opening.
      CONCLUSION: Anatomically, the ejaculatory duct openings of males are located at
      the two sides of the verumontanum adjacent to the opening of the prostatic
      utricle, rather than in the prostatic utricle above the verumontanum.

PMID- 24873161
TI  - [Management of moderate to severe pediatric concealed penis in children by
      Devine's technique via incision between the penis and scrotum].
AB  - OBJECTIVE: To search for a simple and effective surgical approach to the
      management of moderate to severe pediatric concealed penis in children. METHODS:
      We used Devine's technique via incision between the penis and scrotum in the
      treatment of 68 cases of moderate to severe pediatric concealed penis. The
      patients were aged 3 -13 (mean 6.5) years, 30 with moderate and 38 with severe
      pediatric concealed penis. RESULTS: This strategy achieved good near- and long
      term effects and satisfactory appearance of the penis, which was similar to that
      of circumcision. At 3 months after surgery, the penile length was 3 - 5.2 cm,
      averaging (2.35 +/- 0.35) cm. CONCLUSION: Devine's technique via incision between
      the penis and scrotum is a simple and effective surgical option for moderate to
      severe pediatric concealed penis in children.

PMID- 24873162
TI  - [Transumbilical single-site single-port versus single-site double-port
      laparoscopic varicocelectomy for varicocele in adolescents].
AB  - OBJECTIVE: To compare the effect of transumbilical single-site single-port with
      that of transumbilical single-site double-port laparoscopic varicocelectomy in
      the treatment of varicocele in adolescents. METHODS: We randomly assigned 80
      varicocele patients aged 10 - 16 years to two groups of equal number to receive
      transumbilical single-site single-port and single-site double-port laparoscopic
      varicocelectomy, respectively. We compared the operation time, postoperative
      hospital stay, incisional pain, complications and satisfaction with the abdominal
      cosmetic outcomes between the two groups. RESULTS: All the operations were
      successfully performed. The double-port group showed a significantly higher score
      on the Visual Analogue Scale than the single-port group (4.8 +/- 1.4 vs 3.6 +/-
      1.1, t = -4.986, P < 0.01), but there were no significant differences between the
      two groups in the operation time ([29.8 +/- 4.2] vs [31.2 +/- 4.6] min, t =
      1.383, P = 0.171), postoperative hospital stay ([1.95 +/- 0.7] vs [1.82 +/- 0.8]
      d, t = -0.784, P = 0.436), complications (0 vs 0) and scores on the satisfaction
      with abdominal cosmetic outcomes (4.6 +/- 0.6 vs 4.8 +/- 0.5, t = 1.253, P =
      0.214). No recurrence, umbilical hernia, hydrocele and orchiatrophy were found in
      the two groups of patients at 6 months after operation, and no visible scar was
      observed on the abdominal surface. CONCLUSION: With strict surgical indications,
      single-site single-port and single-site double-port laparoscopic
      varicocelectomies have similar clinical effects in the treatment of varicocele,
      which leave no scar on the abdominal surface. Single-site double-port laparoscopy
      needs no special instruments and therefore is worthier of wide clinical
      application.

PMID- 24873163
TI  - [Reproductive hormone levels and relevant parameters in middle-aged and older men
      in the urban area of Nanjing].
AB  - OBJECTIVE: To investigate the status of male reproductive health among middle
      aged and older men in the urban area of Nanjing. METHODS: We collected the
      laboratory results of 884 middle-aged and older men aged 55 - 89 years from the
      Xuanwu District of Nanjing present for routine physical examinations, including
      those of blood routine tests, liver and kidney function, blood glucose, blood
      lipid, and total prostate specific antigen (TPSA), as well as such reproductive
      hormone indexes as total serum testosterone (TT), free serum testosterone (fT),
      and sex hormone binding globulin (SHBG). We also obtained the above reproductive
      hormone indexes from 119 young and middle-aged men aged 20 - 39 years as
      controls. RESULTS: Aging-related changes were found in the 50 percentiles of all
      the reproductive hormones and relevant parameters but those of TT and E2, with
      gradual increases in LH, FSH and SHBG and decreases in fT, TSI and fTI.
      Comparison of reproductive hormones and relevant parameters by Mann-Whitney U
      test did not show any statistically significant differences in the TT level
      between any two of the five age groups (20 - 39, 55 - 59, 60 - 69, 70 - 79, and >
      or = 80 yr) (P > 0.05) except between the control and > or = 80 yr groups and the
      60 - 69 and > or = 80 yr groups (P < 0.05), nor in the E2 level between any two
      groups, nor in the levels of LH and FSH except between the 55 - 59 and 60 - 69 yr
      groups and the 70 - 79 and > or = 80 yr groups, and nor in the levels of fT and
      TSI except between the 55 - 59 and 60 - 69 yr groups. However, there were
      significant differences in the levels of SHBG and fTI between any two age groups.
      Spearman correlation analysis revealed that fT, TSI, and fTI were correlated
      negatively with aging and LH (P < 0.05, I r I > 0.5) but weakly positively with
      cholesterol, blood glucose and hemoglobin (P < 0.05, /r/ < 0.5), SHBG and LH
      positively with aging, SHBG weakly negatively with blood glucose and hemoglobin,
      LH weakly negatively with hemoglobin, and TT weakly negatively with aging but
      positively with hemoglobin. CONCLUSION: The levels of serum testosterone,
      particularly that of fT, declined with aging in middle-aged and older men in the
      urban area of Nanjing, which may contribute to abnormal lipid metabolism, low
      hemoglobin and high blood glucose.

PMID- 24873164
TI  - [Influence of histological prostatitis on the clinical features of benign
      prostatic hyperplasia and prostate cancer].
AB  - OBJECTIVE: To investigate the influence of histological prostatitis (HP) on the
      clinical features of benign prostatic hyperplasia (BPH) and prostate cancer (PCa)
      and its clinical significance. METHODS: We retrospectively studied the data of
      273 cases of BPH and 240 cases of PCa, including age, prostate volume, total
      prostatic special antigen (tPSA), prostatic special antigen density (PSAD),
      maximum urinary flow rate (MFR) and acute urinary retention (AUR). RESULTS:
      Totally, 186 cases of BPH (68.13%) and 45 cases of PCa (18.75%) were complicated
      by HP, with statistically significant difference between the two groups (P <
      0.05). Compared with the patients with BPH only, those complicated by HP showed
      significantly elevated tPSA, PSAD and total prostate volume (all P < 0.05),
      decreased MFR (P < 0.05) and increased risk of AUR (P < 0.05). There was no
      significant difference in the patients' age between the two groups (P > 0.05).
      The levels of tPSA and PSAD were remarkably higher in the PCa patients
      complicated by HP than in those with PCa only (all P < 0.05), but no significant
      differences were found in the other indexes between the two groups (P > 0.05).
      CONCLUSION: HP may play a certain role in the progenesis and progression of HP
      and PCa, but HP is associated more closely with BPH.

PMID- 24873165
TI  - [Penile metastasis from rectal carcinoma: a case report and literature review].
AB  - OBJECTIVE: To improve the diagnosis and treatment of penile metastasis from
      rectal carcinoma. METHODS: We reported a case of penile metastasis secondary to
      rectal adenocarcinoma, reviewed the relevant literature, and discussed the common
      origins, clinical features, pathogenic mechanisms, diagnosis and treatment of
      this disease. RESULTS: The patient was a 54-year-old male, with metastatic penile
      tumors secondary to rectal adenocarcinoma, with serious adhesion to the
      surrounding tissue and metastasis to the liver. As treatment, we performed
      colostomy to relieve voiding difficulty, followed by combination chemotherapy
      with oxaliplatin, 5-fluorouracil, and levofolinate. The patient died 10 months
      later as a result of systemic failure. CONCLUSION: Penile metastatic malignancy
      has a poor prognosis. Early diagnosis and combined and individualized therapies
      may improve the quality of life, relieve pain and prolong the life of the
      patient.

PMID- 24873166
TI  - [Common TCM syndrome pattern of chronic pelvic pain syndrome relates to plasma
      substance p and beta endorphin].
AB  - OBJECTIVE: To investigate the relationship of the common Traditional Chinese
      Medicine (TCM) syndrome pattern of chronic pelvic pain syndrome (CPPS) with the
      contents of substance p and beta endorphin in the plasma, and provide reference
      data for the clinical diagnosis, differentiation and treatment of CPPS by TCM.
      METHODS: We observed 98 cases of CPPS, which were classified into a lower-part
      damp-heat invasion group (group A, n = 32), a blood stasis-induced collateral
      obstruction group (group B, n = 34), and a damp-heat stagnation group (group C, n
      = 32) according to the TCM syndrome differentiation. Another 35 normal healthy
      young men were enrolled as controls. We measured the contents of substance p and
      beta endorphin in the plasma by immunoradiometry and ELISA, and analyzed their
      relationship with the TCM syndrome pattern. RESULTS: The contents of plasma
      substance p were significantly higher in groups A ([1135.76 +/- 166.45] pg/ml), B
      ([1 337.84 +/- 170.81] pg/ml), and C ([1 210.01 +/- 162.27] pg/ml) than in the
      control ([574.99 +/- 113.09] pg/ml) (all P < 0.01), while the contents of plasma
      beta endorphin in groups A ([212.70 +/- 29.49] pg/ml), B ([157.99 +/- 24.01]
      pg/ml), and C ([180.81 +/- 20.20] pg/ml) were remarkably lower than that in the
      control ([274.73 +/- 27.64] pg/ml) (all P < 0.01). CONCLUSION: In the plasma of
      CPPS patients, the content of substance p is significantly elevated and that of
      beta endorphin markedly reduced, which suggests that they may be involved in the
      inflammatory reaction of CPPS. The levels of plasma substance p and beta
      endorphin can be used as valuable reference for the TCM classification of chronic
      prostatitis.

PMID- 24873167
TI  - [UBE2B gene and male infertility: an update].
AB  - Male infertility is a worldwide problem, and about 15% of the cases are
      associated with spermatogenesis-related gene mutation. The mammalian gene UBE2B
      is the homolog of the RAD6 gene of yeast, belonging to the ubiquitin proteasome
      system and playing an important role in spermatogenesis. Mice lacking the UBE2B
      gene are infertile, with reduced sperm motility, increased morphologically
      abnormal sperm, and inhibited meiosis of spermatogonia. Accumulated evidence
      shows that UBE2B gene mutants and single nucleotide polymorphisms are associated
      with male infertility. This article reviews the relation between the UBE2B gene
      and male infertility, offering some theoretical evidence for the diagnosis and
      treatment of male infertility.

PMID- 24873168
TI  - [Updated roles of adrenergic receptors in prostate cancer].
AB  - Adrenergic receptors are members of the G-protein coupled receptor superfamily.
      Recent studies revealed that these adrenergic receptors are playing an important
      role in the growth and metastasis of prostate cancer cells. The expression of
      adrenergic receptors rises significantly in prostate cancer cells and tissues.
      Agonists of these receptors promote the growth and mobility of prostate cancer
      cells, while antagonists may suppress their proliferation, trigger their
      apoptosis, and inhibit their metastasis. Clinically, receptor antagonists can
      significantly reduce the risk of prostate cancer and improve its prognosis after
      androgen depravation therapy. This article presents an overview on the roles of
      adrenergic receptors in prostate cancer.

PMID- 24873191
TI  - Statistical modeling of the drug load distribution on trastuzumab emtansine
      (Kadcyla), a lysine-linked antibody drug conjugate.
AB  - Trastuzumab emtansine (Kadcyla) is a recently approved antibody-drug conjugate
      produced by attachment of the anti-tubulin drug, DM1, to lysine amines via the
      SMCC linker. The resulting product exhibits a drug load distribution from 0 to 8
      drugs per antibody that can be quantified using mass spectrometry. Different
      statistical models were tested against the experimental data derived from samples
      produced during process characterization studies to determine best fit. The
      Poisson distribution gives the best correlation for samples manufactured using
      the target process conditions (yielding the target average drug to antibody ratio
      (DAR) of 3.5) as well as those produced under conditions that exceed the allowed
      manufacturing ranges and yield products with average DAR values that are
      significantly different from the target (i.e., <=3.0 or >=4.0). The Poisson
      distribution establishes a link between average DAR values and drug load
      distributions, implying that measurement and control of the former (i.e., via a
      simple UV spectrophotometric method) could be used to indirectly control the
      latter in trastuzumab emtansine. 

PMID- 24873201
TI  - Cyclodextrin-based host-guest supramolecular nanoparticles for delivery: from
      design to applications.
AB  - CONSPECTUS: Efficient assembly in host-guest interactions is crucial to
      supramolecular nanotechnology. Cyclodextrins (CDs), which possess a hydrophilic
      exterior surface and hydrophobic interior cavity on the truncated cone, improve
      the biocompatibility of nanodelivery systems, and hence, supramolecular
      approaches utilizing CDs can improve and expand the design and applications of
      functional delivery systems. Owing to good inclusion ability, alphaCD and betaCD
      are commonly used in the design and construction of supramolecular structures. In
      this Account, we describe the design strategies to adopt CDs in host-guest
      delivery systems. Modification of CDs with polymers is popular in current
      research due to the potential benefits rendered by cationic protection and
      improved capability. While the process has only minor influence on the host
      characteristics of the CD cavity, the interaction between the CD and the guest
      moiety imparts new attributes to the nanosystems with guest-decorated functional
      groups such as adamantyl poly(ethylene glycol) (PEG) for coating protection,
      hybrid guests for conformational flexibility, and adamantyl prodrugs for drug
      delivery. Some specific agents form inclusion complexes with the polymerized
      betaCDs directly and core-shell nanoparticles with hydrophobic cores and are
      usually created to carry insoluble drugs while the hydrophilic shells offer
      protection. These unique designs provide the means to practically adapt special
      characteristics for additional functions or co-delivery. In order to be accepted
      clinically, delivery systems need to possess extra functions such as controlled
      particle size, biodegradability, controlled release, and targeted delivery to
      overcome the hurdles in delivery. These features can be added to biomaterials by
      self-assembly of functional groups facilitated by the host-guest interactions.
      Size control by hybridization of switchable polymer compartments in
      supramolecular structures contributes to the biodistribution utility and
      biodegradability by incorporating the moieties with hydrolyzable connections and
      enhancing intracellular degradation and clearance. Controlled release by
      application of responsive structures like molecular gatings eased by the host
      guest interaction can be triggered by the tumor microenvironment at extreme pH
      and temperature or by external stimuli such as light. Along with the binding
      selectivity and controlled release, the host-guest nanoparticles show enhanced
      efficacy in delivery especially to tumors. Recent developments in supramolecular
      co-delivery systems are described in this Account. Nanoparticles can be designed
      to carry adamantyl prodrugs and therapeutic nucleotides to tumors so that the
      released drugs and gene expression synergistically inhibit malignant tissue
      growth. Optimization of nanoparticle delivery systems by multifunctional
      transitions yields better biocompatibility and controlled response, and such
      novel designs will expedite in vivo applications. Hence, multifunctional CD-based
      host-guest supramolecular nanoparticles with co-delivery ability are expected to
      have many potential clinical applications.

PMID- 24873177
TI  - Heme utilization by pathogenic bacteria: not all pathways lead to biliverdin.
AB  - The eukaryotic heme oxygenases (HOs) (E.C. 1.14.99.3) convert heme to biliverdin,
      iron, and carbon monoxide (CO) in three successive oxygenation steps. Pathogenic
      bacteria require iron for survival and infection. Extracellular heme uptake from
      the host plays a critical role in iron acquisition and virulence. In the past
      decade, several HOs required for the release of iron from extracellular heme have
      been identified in pathogenic bacteria, including Corynebacterium diphtheriae,
      Neisseriae meningitides, and Pseudomonas aeruginosa. The bacterial enzymes were
      shown to be structurally and mechanistically similar to those of the canonical
      eukaryotic HO enzymes. However, the recent discovery of the structurally and
      mechanistically distinct noncanonical heme oxygenases of Staphylococcus aureus
      and Mycobacterium tuberculosis has expanded the reaction manifold of heme
      degradation. The distinct ferredoxin-like structural fold and extreme heme
      ruffling are proposed to give rise to the alternate heme degradation products in
      the S. aureus and M. tuberculosis enzymes. In addition, several "heme-degrading
      factors" with no structural homology to either class of HOs have recently been
      reported. The identification of these "heme-degrading proteins" has largely been
      determined on the basis of in vitro heme degradation assays. Many of these
      proteins were reported to produce biliverdin, although no extensive
      characterization of the products was performed. Prior to the characterization of
      the canonical HO enzymes, the nonenzymatic degradation of heme and heme proteins
      in the presence of a reductant such as ascorbate or hydrazine, a reaction termed
      "coupled oxidation", served as a model for biological heme degradation. However,
      it was recognized that there were important mechanistic differences between the
      so-called coupled oxidation of heme proteins and enzymatic heme oxygenation. In
      the coupled oxidation reaction, the final product, verdoheme, can readily be
      converted to biliverdin under hydrolytic conditions. The differences between heme
      oxygenation by the canonical and noncanonical HOs and coupled oxidation will be
      discussed in the context of the stabilization of the reactive Fe(III)-OOH
      intermediate and regioselective heme hydroxylation. Thus, in the determination of
      heme oxygenase activity in vitro, it is important to ensure that the reaction
      proceeds through successive oxygenation steps. We further suggest that when
      bacterial heme degradation is being characterized, a systems biology approach
      combining genetics, mechanistic enzymology, and metabolite profiling should be
      undertaken.

PMID- 24873211
TI  - Embedded correlated wavefunction schemes: theory and applications.
AB  - Conspectus Ab initio modeling of matter has become a pillar of chemical research:
      with ever-increasing computational power, simulations can be used to accurately
      predict, for example, chemical reaction rates, electronic and mechanical
      properties of materials, and dynamical properties of liquids. Many competing
      quantum mechanical methods have been developed over the years that vary in
      computational cost, accuracy, and scalability: density functional theory (DFT),
      the workhorse of solid-state electronic structure calculations, features a good
      compromise between accuracy and speed. However, approximate exchange-correlation
      functionals limit DFT's ability to treat certain phenomena or states of matter,
      such as charge-transfer processes or strongly correlated materials. Furthermore,
      conventional DFT is purely a ground-state theory: electronic excitations are
      beyond its scope. Excitations in molecules are routinely calculated using time
      dependent DFT linear response; however applications to condensed matter are still
      limited. By contrast, many-electron wavefunction methods aim for a very accurate
      treatment of electronic exchange and correlation. Unfortunately, the associated
      computational cost renders treatment of more than a handful of heavy atoms
      challenging. On the other side of the accuracy spectrum, parametrized approaches
      like tight-binding can treat millions of atoms. In view of the different (dis
      )advantages of each method, the simulation of complex systems seems to force a
      compromise: one is limited to the most accurate method that can still handle the
      problem size. For many interesting problems, however, compromise proves
      insufficient. A possible solution is to break up the system into manageable
      subsystems that may be treated by different computational methods. The
      interaction between subsystems may be handled by an embedding formalism. In this
      Account, we review embedded correlated wavefunction (CW) approaches and some
      applications. We first discuss our density functional embedding theory, which is
      formally exact. We show how to determine the embedding potential, which replaces
      the interaction between subsystems, at the DFT level. CW calculations are
      performed using a fixed embedding potential, that is, a non-self-consistent
      embedding scheme. We demonstrate this embedding theory for two challenging
      electron transfer phenomena: (1) initial oxidation of an aluminum surface and (2)
      hot-electron-mediated dissociation of hydrogen molecules on a gold surface. In
      both cases, the interaction between gas molecules and metal surfaces were treated
      by sophisticated CW techniques, with the remainder of the extended metal surface
      being treated by DFT. Our embedding approach overcomes the limitations of
      conventional Kohn-Sham DFT in describing charge transfer, multiconfigurational
      character, and excited states. From these embedding simulations, we gained
      important insights into fundamental processes that are crucial aspects of fuel
      cell catalysis (i.e., O2 reduction at metal surfaces) and plasmon-mediated
      photocatalysis by metal nanoparticles. Moreover, our findings agree very well
      with experimental observations, while offering new views into the chemistry. We
      finally discuss our recently formulated potential-functional embedding theory
      that provides a seamless, first-principles way to include back-action onto the
      environment from the embedded region. 

PMID- 24873238
TI  - Visualization by neutron diffraction of 2D oxygen diffusion in the
      Sr(0.7)Ho(0.3)CoO(3-delta) cathode for solid-oxide fuel cells.
AB  - Sr0.7Ho0.3CoO3-delta oxide has been recently described as an excellent cathode
      material (1274 mW cm(-2) at 850  degrees C with pure H2 as fuel1) for solid oxide
      fuel cells (SOFCs) with LSGM as electrolyte. In this work, we describe a detailed
      study of its crystal structure conducted to find out the correlation between the
      excellent performance as a cathode and the structural features. The tetragonal
      crystal structure (e.g., I4/mmm) basically contains layers of octahedrally
      coordinated Co2O6 units alternated with layers of Co1O4 tetrahedra sharing
      corners. An "in situ" neutron power diffraction (NPD) experiment, between 25 and
      800  degrees C, reveals the presence of a high oxygen deficiency affecting O4
      oxygen atoms, with large displacement factors that suggest a large lability and
      mobility. Difference Fourier maps allow the visualization at high temperatures of
      the 2D diffusion pathways within the tetrahedral layers, where O3 and O4 oxygens
      participate. The measured thermal expansion coefficient is 16.61 * 10(-6) K(-1)
      between 300 and 850  degrees C, exhibiting an excellent chemical compatibility
      with the electrolyte. 

PMID- 24873234
TI  - Exercises in molecular computing.
AB  - CONSPECTUS: The successes of electronic digital logic have transformed every
      aspect of human life over the last half-century. The word "computer" now
      signifies a ubiquitous electronic device, rather than a human occupation. Yet
      evidently humans, large assemblies of molecules, can compute, and it has been a
      thrilling challenge to develop smaller, simpler, synthetic assemblies of
      molecules that can do useful computation. When we say that molecules compute,
      what we usually mean is that such molecules respond to certain inputs, for
      example, the presence or absence of other molecules, in a precisely defined but
      potentially complex fashion. The simplest way for a chemist to think about
      computing molecules is as sensors that can integrate the presence or absence of
      multiple analytes into a change in a single reporting property. Here we review
      several forms of molecular computing developed in our laboratories. When we began
      our work, combinatorial approaches to using DNA for computing were used to search
      for solutions to constraint satisfaction problems. We chose to work instead on
      logic circuits, building bottom-up from units based on catalytic nucleic acids,
      focusing on DNA secondary structures in the design of individual circuit
      elements, and reserving the combinatorial opportunities of DNA for the
      representation of multiple signals propagating in a large circuit. Such circuit
      design directly corresponds to the intuition about sensors transforming the
      detection of analytes into reporting properties. While this approach was unusual
      at the time, it has been adopted since by other groups working on biomolecular
      computing with different nucleic acid chemistries. We created logic gates by
      modularly combining deoxyribozymes (DNA-based enzymes cleaving or combining other
      oligonucleotides), in the role of reporting elements, with stem-loops as input
      detection elements. For instance, a deoxyribozyme that normally exhibits an
      oligonucleotide substrate recognition region is modified such that a stem-loop
      closes onto the substrate recognition region, making it unavailable for the
      substrate and thus rendering the deoxyribozyme inactive. But a conformational
      change can then be induced by an input oligonucleotide, complementary to the
      loop, to open the stem, allow the substrate to bind, and allow its cleavage to
      proceed, which is eventually reported via fluorescence. In this Account, several
      designs of this form are reviewed, along with their application in the
      construction of large circuits that exhibited complex logical and temporal
      relationships between the inputs and the outputs. Intelligent (in the sense of
      being capable of nontrivial information processing) theranostic (therapy +
      diagnostic) applications have always been the ultimate motivation for developing
      computing (i.e., decision-making) circuits, and we review our experiments with
      logic-gate elements bound to cell surfaces that evaluate the proximal presence of
      multiple markers on lymphocytes.

PMID- 24873257
TI  - Synthesis of porous ZnS:Ag2S nanosheets by ion exchange for photocatalytic H2
      generation.
AB  - ZnS:Ag2S porous nanostructures are prepared by a simple ion-exchange route using
      ZnS nanosheets as sacrificial templates. In solutions of different Ag ion
      concentrations, ZnS nanosheets are partially converted to Ag2S, resulting in
      porous ZnS:Ag2S nanosheet composites with different pore sizes. With the Ag2S
      nanocrystals playing the role of hole scavengers, the porous nanosheets exhibit a
      high photocatalytic H2 generation rate of 104.9 MUmol/h/g without using any noble
      metal cocatalyst. 

PMID- 24873275
TI  - Mesoporous gold and palladium nanoleaves from liquid-liquid interface: enhanced
      catalytic activity of the palladium analogue toward hydrazine-assisted room
      temperature 4-nitrophenol reduction.
AB  - The importance of an interfacial reaction to obtain mesoporous leafy
      nanostructures of gold and palladium has been reported. A new synthetic strategy
      involving 1,4-dihydropyridine ester (DHPE) as a potential reducing agent performs
      exceptionally well for the desired morphologies of both the noble metals at room
      temperature. The DHPE in turn transforms into its oxidized aromatic form. The as
      synthesized gold leaves exhibit high surface-enhanced Raman scattering activity
      with rhodamine 6G (R6G) due to their hyperbranched structure. It is worthwhile
      that as-synthesized porous architectures of palladium support the room
      temperature hydrogenation of 4-nitrophenol (4-NP) by hydrazine hydrate
      (N2H4.H2O), reported for the first time. Furthermore, MPL exhibits exceptionally
      good catalytic activity toward electrooxidation of formic acid. Therefore, an
      aromaticity driven synthetic technique achieves a rationale to design leafy
      nanostructures of noble metals from the liquid-liquid interface for multifaceted
      applications. 

PMID- 24873259
TI  - A flexible glutamine regulates the catalytic activity of toluene o-xylene
      monooxygenase.
AB  - Toluene/o-xylene monooxygenase (ToMO) is a bacterial multicomponent monooxygenase
      capable of oxidizing aromatic substrates. The carboxylate-rich diiron active site
      is located in the hydroxylase component of ToMO (ToMOH), buried 12 A from the
      surface of the protein. A small, hydrophilic pore is the shortest pathway between
      the diiron active site and the protein exterior. In this study of ToMOH from
      Pseudomonas sp. OX1, the functions of two residues lining this pore, N202 and
      Q228, were investigated using site-directed mutagenesis. Steady-state
      characterization of WT and the three mutant enzymes demonstrates that residues
      N202 and Q228 are critical for turnover. Kinetic isotope effects and pH profiles
      reveal that these residues govern the kinetics of water egress and prevent
      quenching of activated oxygen intermediates formed at the diiron active site. We
      propose that this activity arises from movement of these residues, opening and
      closing the pore during catalysis, as seen in previous X-ray crystallographic
      studies. In addition, N202 and Q228 are important for the interactions of the
      reductase and regulatory components to ToMOH, suggesting that they bind
      competitively to the hydroxylase. The role of the pore in the hydroxylase
      components of other bacterial multicomponent monooxygenases within the
      superfamily is discussed in light of these conclusions. 

PMID- 24873290
TI  - Solid-state photogalvanic dye-sensitized solar cells.
AB  - Photogalvanic cells are photoelectrochemical systems wherein the semiconductor
      electrode is not a participant in primary photoinduced charge formation. The
      discovery of photoelectrochemical systems that successfully exploit secondary
      (thermal) electron injection at dye-semiconductor interfaces may enable studies
      of electron transfer at minimal driving force for electron injection into the
      semiconductor. In this study, we have examined thermal electron transfer from
      molecular sensitizers to nanostructured semiconductor electrodes composed of
      titanium dioxide nanorods by means of transient spectroscopy and the assembly and
      testing of photoelectrochemical cells. Electron-accepting molecular dyes have
      been studied alongside an arylamine electron donor. Thermal injection is
      estimated for a naphthacenequinone radical anion as a multiexponential decay
      process with initial decay lifetimes of 6 and 27 ps. The ambient electric field
      present during charge separation at a surface-adsorbed dye monolayer causes Stark
      shifts of the radical ion pair absorbance peaks that confounded kinetic
      estimation of thermal injection for a fullerene sensitizer. Electron-accepting
      dyes that operate by thermal injection into titanium dioxide function better in
      solid-state photoelectrochemical cells than in liquid-junction cells due to the
      kinetic advantage of solid-state cells with respect to photoinduced acceptor
      quenching to form the necessary radical anion sensitizers. 

PMID- 24873296
TI  - Redox deposition of birnessite-type manganese oxide on silicon carbide
      microspheres for use as supercapacitor electrodes.
AB  - Silicon carbide microsphere/birnessite-type MnOx (SiC/B-MnOx) composites were
      prepared by removal of a SiO2 layer with redox deposition of birnessite-type MnOx
      for supercapacitor electrode materials. The characterization studies showed that
      the birnessite-type MnOx in the composite was homogeneously deposited on the SiC
      surface. The capacitive properties of the as-prepared SiC/B-MnOx electrodes were
      measured in a three-electrode system using 1 M Na2SO4(aq) as the electrolyte. The
      SiC/B-MnOx(6) electrode, fabricated using a MnOx/SiC feeding ratio of 6:1,
      displayed a specific capacitance of 251.3 F g(-1) at 10 mV s(-1). Such excellent
      electrochemical performance is attributed to an increase in the electrical
      conductivity in the presence of silicon carbide, an increase in the effective
      interfacial area between MnOx and the electrolyte, and the contact area between
      MnOx and silicon carbide. The deposition of birnessite-type MnOx on a SiC surface
      may be a prospective fabrication technique for electrode materials for
      supercapacitors. 

PMID- 24873315
TI  - Self-assembled three-dimensional hierarchical graphene/polypyrrole nanotube
      hybrid aerogel and its application for supercapacitors.
AB  - A three-dimensional hierarchical graphene/polypyrrole aerogel (GPA) has been
      fabricated using graphene oxide (GO) and already synthesized one-dimensional
      hollow polypyrrole nanotubes (PNTs) as the feedstock. The amphiphilic GO is
      helpful in effectively promoting the dispersion of well-defined PNTs to result in
      a stable, homogeneous GO/PNT complex solution, while the PNTs not only provide a
      large accessible surface area for fast transport of hydrate ions but also act as
      spacers to prevent the restacking of graphene sheets. By a simple one-step
      reduction self-assembly process, hierarchically structured, low-density, highly
      compressible GPAs are easily obtained, which favorably combine the advantages of
      graphene and PNTs. The supercapacitor electrodes based on such materials exhibit
      excellent electrochemical performance, including a high specific capacitance up
      to 253 F g(-1), good rate performance, and outstanding cycle stability. Moreover,
      this method may be feasible to prepare other graphene-based hybrid aerogels with
      structure-controllable nanostructures in large scale, thereby holding enormous
      potential in many application fields. 

PMID- 24873318
TI  - Manufacturable conducting rubber ambers and stretchable conductors from copper
      nanowire aerogel monoliths.
AB  - We report on a low-cost, simple yet efficient strategy to fabricate
      ultralightweight aerogel monoliths and conducting rubber ambers from copper
      nanowires (CuNWs). A trace amount of poly(vinyl alcohol) (PVA) substantially
      improved the mechanical robustness and elasticity of the CuNW aerogel while
      maintaining a high electrical conductivity. The resistivity was highly responsive
      to strains manifesting two distinct domains, and both followed a power law
      function consistent with pressure-controlled percolation theory. However, the
      values of the exponents were much less than the predicted value for 3D systems,
      which may be due to highly porous structures. Remarkably, the CuNW-PVA aerogels
      could be further embedded into PDMS resin, forming conducting rubber ambers. The
      ambers could be further manufactured simply by cutting into any arbitrary 1D, 2D,
      and 3D shapes, which were all intrinsically conductive without the need of
      external prewiring, a condition required in the previous aerogel-based
      conductors. The outstanding electrical conductivity in conjunction with high
      mechanical compliance enabled prototypes of the elastic piezoresistivity switches
      and stretchable conductors. 

PMID- 24873326
TI  - Bordetella pertussis FbpA binds both unchelated iron and iron siderophore
      complexes.
AB  - Bordetella pertussis is the causative agent of whooping cough. This pathogenic
      bacterium can obtain the essential nutrient iron using its native alcaligin
      siderophore and by utilizing xeno-siderophores such as desferrioxamine B,
      ferrichrome, and enterobactin. Previous genome-wide expression profiling
      identified an iron repressible B. pertussis gene encoding a periplasmic protein
      (FbpABp). A previously reported crystal structure shows significant similarity
      between FbpABp and previously characterized bacterial iron binding proteins, and
      established its iron-binding ability. Bordetella growth studies determined that
      FbpABp was required for utilization of not only unchelated iron, but also
      utilization of iron bound to both native and xeno-siderophores. In this in vitro
      solution study, we quantified the binding of unchelated ferric iron to FbpABp in
      the presence of various anions and importantly, we demonstrated that FbpABp binds
      all the ferric siderophores tested (native and xeno) with MUM affinity. In silico
      modeling augmented solution data. FbpABp was incapable of iron removal from
      ferric xeno-siderophores in vitro. However, when FbpABp was reacted with native
      ferric-alcaligin, it elicited a pronounced change in the iron coordination
      environment, which may signify an early step in FbpABp-mediated iron removal from
      the native siderophore. To our knowledge, this is the first time the periplasmic
      component of an iron uptake system has been shown to bind iron directly as Fe(3+)
      and indirectly as a ferric siderophore complex. 

PMID- 24873348
TI  - Enhanced permittivity and energy density in neat poly(vinylidene fluoride
      trifluoroethylene-chlorotrifluoroethylene) terpolymer films through control of
      morphology.
AB  - Polymer materials with large dielectric constants are desirable for the
      development of high energy density capacitors. We show that the dielectric
      properties of poly(vinylidene fluoride-trifluoroethylene-chlorotrifluoroethylene)
      [P(VDF-TrFE-CTFE)] can be improved by the use of processing conditions that favor
      formation of a highly crystalline morphology of the nonpolar alpha-phase. Through
      the use of spin coating, thermal treatment above the melting temperature, and
      quenching, we were able to attain a highly crystalline, alpha-phase rich
      morphology that has a quite large dielectric constant of 77 +/- 10 at 1 kHz. The
      final morphology and phase composition of the terpolymer films depend strongly on
      the postprocessing thermal treatment and the quality of the solvent. Evaluation
      of the polarization behavior of the terpolymer films as a function of electric
      field reveal that the polymer exhibits a relaxor-ferroelectric behavior and has a
      substantial energy density of 9.7 J/cm(3) at fields of up to approximately 470
      V/MUm. Under millisecond pulsed charge-discharge measurements a 3-fold increase
      in energy density (27 J/cm(3)) is obtained at high fields (~600 V/MUm). Our study
      demonstrates that the processing conditions and morphology of fluorinated
      terpolymer films are controlling factors for achievement of high dielectric
      permittivity and energy density that are critical for high performance
      capacitors. 

PMID- 24873330
TI  - Hybrid wood materials with magnetic anisotropy dictated by the hierarchical cell
      structure.
AB  - Anisotropic and hierarchical structures are bound in nature and highly desired in
      engineered materials, due to their outstanding functions and performance.
      Mimicking such natural features with synthetic materials and methods has been a
      highly active area of research in the last decades. Unlike these methods, we use
      the native biomaterial wood, with its intrinsic anisotropy and hierarchy as a
      directional scaffold for the incorporation of magnetic nanoparticles inside the
      wood material. Nanocrystalline iron oxide particles were synthesized in situ via
      coprecipitation of ferric and ferrous ions within the interconnected pore network
      of bulk wood. Imaging with low-vacuum and cryogenic electron microscopy as well
      as spectral Raman mapping revealed layered nanosize particles firmly attached to
      the inner surface of the wood cell walls. The mineralogy of iron oxide was
      identified by XRD powder diffraction and Raman spectroscopy as a mixture of the
      spinel phases magnetite and maghemite. The intrinsic structural architecture of
      native wood entails a three-dimensional assembly of the colloidal iron oxide
      which results in direction-dependent magnetic features of the wood-mineral hybrid
      material. This superinduced magnetic anisotropy, as quantified by direction
      dependent magnetic hysteresis loops and low-field susceptibility tensors, allows
      for directional lift, drag, alignment, (re)orientation, and actuation, and opens
      up novel applications of the natural resource wood. 

PMID- 24873372
TI  - Inverted nanocone-based thin film photovoltaics with omnidirectionally enhanced
      performance.
AB  - Thin film photovoltaic (PV) technologies are highly attractive for low-cost solar
      energy conversion and possess a wide range of potential applications from
      building-integrated PV generation to portable power sources. Inverted nanocones
      (i-cones) have been demonstrated as a promising structure for practical thin film
      PV devices/modules, owning to their antireflection effect, self-cleaning
      function, superior mechanical robustness, and so forth. In this work, we have
      demonstrated a low-cost and scalable approach to achieve perfectly ordered i-cone
      arrays. Thereafter, thin film amorphous silicon (a-Si:H) solar cells have been
      fabricated based on various i-cone substrates with different aspect ratios and
      pitches to investigate the impact of geometry of i-cone nanostructures on the
      performance of the as-obtained PV devices. Intriguingly, the optical property
      investigations and device performance characterizations demonstrated that the 0.5
      aspect-ratio i-cone-based device performed the best on both light absorption
      capability and energy conversion efficiency, which is 34% higher than that of the
      flat counterpart. Moreover, the i-cone-based device enhanced the light absorption
      and device performance over the flat reference device omnidirectionally. These
      results demonstrate a viable and convenient route toward scalable fabrication of
      nanostructures for high-performance thin film PV devices based on a broad range
      of materials. 

PMID- 24873349
TI  - Highly sensitive single domain antibody-quantum dot conjugates for detection of
      HER2 biomarker in lung and breast cancer cells.
AB  - Despite the widespread availability of immunohistochemical and other
      methodologies for screening and early detection of lung and breast cancer
      biomarkers, diagnosis of the early stage of cancers can be difficult and prone to
      error. The identification and validation of early biomarkers specific to lung and
      breast cancers, which would permit the development of more sensitive methods for
      detection of early disease onset, is urgently needed. In this paper, ultra-small
      and bright nanoprobes based on quantum dots (QDs) conjugated to single domain
      anti-HER2 (human epidermal growth factor receptor 2) antibodies (sdAbs) were
      applied for immunolabeling of breast and lung cancer cell lines, and their
      performance was compared to that of anti-HER2 monoclonal antibodies conjugated to
      conventional organic dyes Alexa Fluor 488 and Alexa Fluor 568. The sdAbs-QD
      conjugates achieved superior staining in a panel of lung cancer cell lines with
      differential HER2 expression. This shows their outstanding potential for the
      development of more sensitive assays for early detection of cancer biomarkers. 

PMID- 24873373
TI  - New insights into the microstructure-separation properties of organosilica
      membranes with ethane, ethylene, and acetylene bridges.
AB  - Microporous organosilica membranes with ethane, ethylene, and acetylene bridges
      have been developed and the extensive microstructural characterization has been
      discussed in relation with separation properties of the membrane. The
      organosilica network structure and the membrane performances can be controlled by
      adjusting the flexibility, size, and electronic structure of the bridging groups.
      A relatively narrow size distribution was obtained for the novel acetylene
      bridged sol by optimizing the sol synthesis. Incorporation of larger rigid
      bridges into organosilica networks resulted in a looser microstructure of the
      membrane, which was quantitatively evaluated by N2 sorption and positron
      annihilation lifetime (PAL) measurements. Molecular weight cutoff (MWCO)
      measurements indicated that the acetylene-bridged membrane had a larger effective
      separation pore size than ethane- and ethylene-bridged membranes, leading to a
      relatively low NaCl rejection in reverse osmosis. In quantum chemical
      calculations, a more open pore structure and increased polarization was observed
      for the acetylene-bridged networks, which led to a significant improvement in
      water permeability. The present study will offer new insight into design of high
      performance molecular separation membranes. 

PMID- 24873393
TI  - Graphene synthesis via thermal polymerization of aromatic quinone molecules.
AB  - Graphene was synthesized from pentacenequinone molecules on a Cu(111) surface
      using a three-step thermal treatment process: (1) self-assembly of a single layer
      molecular film at 190  degrees C, (2) formation of covalent bonding between
      adjacent molecules at intermediate temperatures, (3) thermal dehydrogenation and
      in-plane carbon diffusion at 600  degrees C. Transformation of the surface
      conformation was monitored with bimodal atomic force microscopy at the atomic
      scale and was corroborated with core-level X-ray photoelectron spectroscopy. A
      strong C?O...H-C hydrogen bonding involving the quinone moiety plays a key role
      in graphene growth, whereas conventional pentacene simply desorbs from the
      substrate during the same process. The most significant achievement of this
      proposed technique is obtaining graphene a couple of hundred degrees lower than
      standard techniques. Intrinsic defects due to carbon deficiency and the defects
      intentionally introduced by the microscope tip were also investigated with atomic
      scale imaging. 

PMID- 24873395
TI  - Enhanced tribological, corrosion, and microstructural properties of an ultrathin
      (<2 nm) silicon nitride/carbon bilayer overcoat for high density magnetic
      storage.
AB  - An ultrathin bilayer overcoat of silicon nitride and carbon (SiNx/C) providing
      low friction, high wear resistance, and high corrosion resistance is proposed for
      future generation hard disk media. The 16 A thick SiNx/C overcoat consists of an
      atomically thin SiNx underlayer (4 A) and a carbon layer (12 A), fabricated by
      reactive magnetron sputtering and filtered cathodic vacuum arc (FCVA),
      respectively. When compared with monolithic overcoats of FCVA-deposited carbon
      (16 A) and sputtered SiNx (16 A), the SiNx/C bilayer overcoat demonstrated the
      best tribological performance with a coefficient of friction < 0.2. Despite
      showing marginally less electrochemical corrosion protection than monolithic
      SiNx, its ability to protect the magnetic media from corrosion/oxidation was
      better than that of an ~27 A thick commercial hard disk overcoat and 16 A thick
      monolithic FCVA-deposited carbon. From X-ray photoelectron spectroscopy and Raman
      spectroscopy analyses, it was found that the introduction of the 4 A SiNx
      underlayer facilitated higher sp(3) hybridization within the carbon layer by
      acting as a barrier and promoted the formation of strong bonds at the SiNx/C and
      the SiNx/media interfaces by acting as an adhesion layer. The higher sp(3) carbon
      content is expected to improve the thermal stability of the overcoat, which is
      extremely important for future hard disk drives employing heat assisted magnetic
      recording (HAMR). 

PMID- 24873380
TI  - Regulation of nonmuscle myosin II by tropomyosin.
AB  - The actin cytoskeleton carries out cellular functions, including division,
      migration, adhesion, and intracellular transport, that require a variety of actin
      binding proteins, including myosins. Our focus here is on class II nonmuscle
      myosin isoforms, NMIIA, NMIIB, and NMIIC, and their regulation by the actin
      binding protein, tropomyosin. NMII myosins are localized to different populations
      of stress fibers and the contractile ring, structures involved in force
      generation required for cell migration, adhesion, and cytokinesis. The stress
      fibers and contractile ring that contain NMII myosins also contain tropomyosin.
      Four mammalian genes encode more than 40 tropomyosins. Tropomyosins inhibit or
      activate actomyosin MgATPase and motility depending on the myosin and tropomyosin
      isoform. In vivo, tropomyosins play a role in cell migration, adhesion,
      cytokinesis, and NMII isoform localization in an isoform-specific manner. We
      postulate that the isoform-specific tropomyosin localization and effect on NMII
      isoform localization reflect modulation of NMII actomyosin kinetics and motile
      function. In this study, we compare the ability of different tropomyosin isoforms
      to support actin filament motility with NMIIA, NMIIB, and NMIIC as well as
      skeletal muscle myosin. Tropomyosins activated, inhibited, or had no effect on
      motility depending on the myosin, indicating that the myosin isoform is the
      primary determinant of the isoform-specific effect of tropomyosin on actomyosin
      regulation. Activation of motility of nonmuscle tropomyosin-actin filaments by
      NMII myosin correlates with an increased Vmax of the myosin MgATPase, implying a
      direct effect on the myosin MgATPase, in contrast to the skeletal tropomyosin
      actin filament that has no effect on the Vmax or maximal filament velocity. 

PMID- 24873414
TI  - Heterogeneous assembled nanocomplexes for ratiometric detection of highly
      reactive oxygen species in vitro and in vivo.
AB  - Probes for detecting highly reactive oxygen species (hROS) are critical to both
      understanding the etiology of the disease and optimizing therapeutic
      interventions. However, problems such as low stability due to autoxidation and
      photobleaching and unsuitability for biological application in vitro and in vivo,
      as well as the high cost and complex procedure in synthesis and modification,
      largely limit their application. In this work, binary heterogeneous nanocomplexes
      (termed as C-dots-AuNC) constructed from gold clusters and carbon dots were
      reported. The fabrication takes full advantages of the inherent active groups on
      the surface of the nanoparticles to avoid tedious modification and chemical
      synthetic processes. Additionally, the assembly endowed C-dots-AuNC with improved
      performance such as the fluorescence enhancement of AuNCs and stability of C-dots
      to hROS. Moreover, the dual-emission property allows sensitive imaging and
      monitoring of the hROS signaling in living cells with high contrast. Importantly,
      with high physiological stability and excellent biocompatibility, C-dots-AuNC
      allows for the detection of hROS in the model of local ear inflammation. 

PMID- 24873420
TI  - Account of nitroarene reduction with size- and facet-controlled CuO-MnO2
      nanocomposites.
AB  - In this work, we propose a systematic and delicate size- and shape-controlled
      synthesis of CuO-MnO2 composite nanostructures from time-dependent redox
      transformation reactions between Cu2O and KMnO4. The parental size and shape of
      Cu2O nanostructures are retained, even after the redox transformation, but the
      morphology becomes porous in nature. After prolonged reaction times (>24 h), the
      product shapes are ruptured, and as a result, tiny spherical porous
      nanocomposites of ~100 nm in size are obtained. This method is highly
      advantageous due to its low cost, its easy operation, and a surfactant or
      stabilizing agent-free approach with high reproducibility, and it provides a
      facile but new way to fabricate porous CuO-MnO2 nanocomposites of varied shape
      and size. The composite nanomaterials act as efficient recyclable catalysts for
      nitroarene reduction in water at room temperature. The time-dependent reduction
      kinetics can be easily monitored by using UV-vis spectrophotometer. The catalytic
      system is found to be very useful toward the reduction of nitro compounds,
      regardless of the type and position of the substituent(s). Furthermore, it is
      revealed that CuO-MnO2 composite nanomaterials exhibit facet-dependent catalytic
      activity toward nitroarene reduction, where the (111) facet of the composite
      stands to be more active than that of the (100) facet. The results are also
      corroborated from the BET surface area measurements. It is worthwhile to mention
      that porous tiny spheres (product of 48 h reaction) exhibit the highest catalytic
      activity due to pronounced surface area and smaller size. 

PMID- 24873459
TI  - Development of a cyclic system for chemiluminescence detection.
AB  - In this paper, we described a new concept of cyclic chemiluminescence (CCL)
      detection, and a homemade system was designed to realize such detection. The
      direction of the carrier in the CCL system is in a state of periodical change
      that can trigger a succession of chemiluminescence (CL) reactions in a single
      sample injection. Therefore, in contrast to the traditional CL detection, which
      only records a single signal, CCL allows us to obtain multistage signals. To
      evaluate the new method, the cataluminescence (CTL) reaction of the volatile
      organic compounds (VOCs) on a nanosized catalyst was selected as the analytical
      model. We found that each CCL reaction has a unique exponential decay equation
      (EDE) to describe the change law of its multistage signals. Further study showed
      that the initial amount (A) of the EDE is linear with the analyte concentration,
      while the decay coefficient (k) is a characteristic constant for a given
      reaction. The formation mechanism of the exponential function and the
      determinants of the decay coefficient were discussed in detail. As a distinct
      application, CCL is capable of rapidly discriminating various analytes and even
      structural isomers. 

PMID- 24873435
TI  - Quantification of HIV-1 DNA using real-time recombinase polymerase amplification.
AB  - Although recombinase polymerase amplification (RPA) has many advantages for the
      detection of pathogenic nucleic acids in point-of-care applications, RPA has not
      yet been implemented to quantify sample concentration using a standard curve.
      Here, we describe a real-time RPA assay with an internal positive control and an
      algorithm that analyzes real-time fluorescence data to quantify HIV-1 DNA. We
      show that DNA concentration and the onset of detectable amplification are
      correlated by an exponential standard curve. In a set of experiments in which the
      standard curve and algorithm were used to analyze and quantify additional DNA
      samples, the algorithm predicted an average concentration within 1 order of
      magnitude of the correct concentration for all HIV-1 DNA concentrations tested.
      These results suggest that quantitative RPA (qRPA) may serve as a powerful tool
      for quantifying nucleic acids and may be adapted for use in single-sample point
      of-care diagnostic systems. 

PMID- 24873475
TI  - Superhydrophobic stability of nanotube array surfaces under impact and static
      forces.
AB  - The surfaces of nanotube arrays were coated with poly(methyl methacrylate) (PMMA)
      using an imprinting method with an anodized alumina membrane as the template. The
      prepared nanotube array surfaces then either remained untreated or were coated
      with NH2(CH2)3Si(OCH3)3(PDNS) or CF3(CF2)7CH2CH2Si(OC2H5)3 (PFO). Thus, nanotube
      arrays with three different surfaces, PDNS, PMMA (without coating), and PFO, were
      obtained. All three surfaces (PDNS, PMMA, and PFO) exhibited superhydrophobic
      properties with contact angles (CA) of 155, 166, and 168 degrees , respectively,
      and their intrinsic water contact angles were 30, 79, and 118 degrees ,
      respectively. The superhydrophobic stabilities of these three surfaces were
      examined under dynamic impact and static pressures in terms of the transition
      from the Cassie-Baxter mode to the Wenzel mode. This transition was determined by
      the maximum pressure (p(max)), which is dependent on the intrinsic contact angle
      and the nanotube density of the surface. A p(max) greater than 10 kPa, which is
      sufficiently large to maintain stable superhydrophobicity under extreme weather
      conditions, such as in heavy rain, was expected from the PFO surface.
      Interestingly, the PDNS surface, with an intrinsic CA of only 30 degrees , also
      displayed superhydrophobicity, with a CA of 155 degrees . This property was
      partially maintained under the dynamic impact and static pressure tests. However,
      under an extremely high pressure (0.5 MPa), all three surfaces transitioned from
      the Cassie-Baxter mode to the Wenzel mode. Furthermore, the lost
      superhydrophobicity could not be recovered by simply relieving the pressure. This
      result indicates that the best way to maintain superhydrophobicity is to increase
      the p(max) of the surface to a value higher than the applied external pressure by
      using low surface energy materials and having high-density binary nano
      /microstructures on the surface.

PMID- 24873476
TI  - Small but powerful: co-assembly of polyether-based triblock terpolymers into sub
      30 nm micelles and synergistic effects on cellular interactions.
AB  - We introduce a versatile ABC triblock terpoly- mer platform based on
      poly(ethylene oxide)-block-poly(allyl glycidyl ether)-block-poly(tert-butyl
      glycidyl ether) (PEO-b-PAGE-b-PtBGE) and subsequent functionalization of the PAGE
      segment with thiogalactose (hydroxyl), cysteamine (amino), and 2
      mercaptopropionic acid (carboxy) by thiol-ene chemistry. These materials are used
      to prepare core-shell-corona micelles with a PtBGE core, a PAGE shell, and a PEO
      corona and sizes below 30 nm in aqueous media. We investigate the influence of
      different functional groups on micelle formation and cellular uptake. Moreover,
      co-assembly of differently functionalized materials allows to create micelles
      with a mixed shell and adjustable charge and, in that way, important
      characteristics such as cell uptake or cytotoxicity can be controlled.
      Furthermore, we demonstrate that even the uptake mechanism depends on the
      substitution pattern of the underlying triblock terpolymer. 

PMID- 24873489
TI  - Biologically driven synthesis of pyrazolo[3,4-d]pyrimidines as protein kinase
      inhibitors: an old scaffold as a new tool for medicinal chemistry and chemical
      biology studies.

PMID- 24873478
TI  - Microgel mechanics in biomaterial design.
AB  - The field of polymeric biomaterials has received much attention in recent years
      due to its potential for enhancing the biocompatibility of systems and devices
      applied to drug delivery and tissue engineering. Such applications continually
      push the definition of biocompatibility from relatively straightforward issues
      such as cytotoxicity to significantly more complex processes such as reducing
      foreign body responses or even promoting/recapitulating natural body functions.
      Hydrogels and their colloidal analogues, microgels, have been and continue to be
      heavily investigated as viable materials for biological applications because they
      offer numerous, facile avenues in tailoring chemical and physical properties to
      approach biologically harmonious integration. Mechanical properties in particular
      are recently coming into focus as an important manner in which biological
      responses can be altered. In this Account, we trace how mechanical properties of
      microgels have moved into the spotlight of research efforts with the realization
      of their potential impact in biologically integrative systems. We discuss early
      experiments in our lab and in others focused on synthetic modulation of particle
      structure at a rudimentary level for fundamental drug delivery studies. These
      experiments elucidated that microgel mechanics are a consequence of polymer
      network distribution, which can be controlled by chemical composition or particle
      architecture. The degree of deformability designed into the microgel allows for a
      defined response to an imposed external force. We have studied deformation in
      packed colloidal phases and in translocation events through confined pores; in
      all circumstances, microgels exhibit impressive deformability in response to
      their environmental constraints. Microgels further translate their mechanical
      properties when assembled in films to the properties of the bulk material. In
      particular, microgel films have been a large focus in our lab as building blocks
      for self-healing materials. We have shown that their ability to heal after damage
      arises from polymer mobility during hydration. Furthermore, we have shown film
      mobility dictates cell adhesion and spreading in a manner that is fundamentally
      different from previous work on mechanotransduction. In total, we hope that this
      Account presents a broad introduction to microgel research that intersects
      polymer chemistry, physics, and regenerative medicine. We expect that research
      intersection will continue to expand as we fill the knowledge gaps associated
      with soft materials in biological milieu.

PMID- 24873495
TI  - Generalized energy-based fragmentation approach and its applications to
      macromolecules and molecular aggregates.
AB  - Conspectus The generalized energy-based fragmentation (GEBF) approach provides a
      very simple way of approximately evaluating the ground-state energy or properties
      of a large system in terms of ground-state energies of various small
      "electrostatically embedded" subsystems, which can be calculated with any
      traditional ab initio quantum chemistry (X) method (X = Hartree-Fock, density
      functional theory, and so on). Due to its excellent parallel efficiency, the GEBF
      approach at the X theory level (GEBF-X) allows full quantum mechanical (QM)
      calculations to be accessible for systems with hundreds and even thousands of
      atoms on ordinary workstations. The implementation of the GEBF approach at
      various theoretical levels can be easily done with existing quantum chemistry
      programs. This Account reviews the methodology, implementation, and applications
      of the GEBF-X approach. This method has been successfully applied to optimize the
      structures of various large systems including molecular clusters, polypeptides,
      proteins, and foldamers. Such investigations could allow us to elucidate the
      origin and nature of the cooperative interaction in secondary structures of long
      peptides or the driving force of the self-assembly processes of aromatic
      oligoamides. These GEBF-based QM calculations reveal that the structures and
      stability of various complex systems result from a subtle balance of many types
      of noncovalent interactions such as hydrogen bonding and van der Waals
      interactions. The GEBF-based ab initio molecular dynamics (AIMD) method also
      allows the investigation of dynamic behaviors of large systems on the order of
      tens of picoseconds. It was demonstrated that the conformational dynamics of two
      model peptides predicted by GEBF-based AIMD are noticeably different from those
      predicted by the classical force field MD method. With the target of extending QM
      calculations to molecular aggregates in the condensed phase, we have implemented
      the GEBF-based multilayer hybrid models, which could provide satisfactory
      descriptions of the binding energies between a solute molecule and its
      surrounding waters and the chain-length dependence of the conformational changes
      of oligomers in aqueous solutions. A coarse-grained polarizable molecular
      mechanics model, furnished with GEBF-X dipole moments of subsystems, exhibits
      some advantages of treating the electrostatic polarization with reduced
      computational costs. We anticipate that the GEBF approach will continue to
      develop with the ultimate goal of studying complicated phenomena at mesoscopic
      scales and serve as a practical tool to elucidate the structure and dynamics of
      chemical and biological systems. 

PMID- 24873498
TI  - Enhancement of the efficiency of photocatalytic reduction of protons to hydrogen
      via molecular assembly.
AB  - Conspectus One of the best solutions for meeting future energy demands is the
      conversion of water into hydrogen fuel using solar energy. The splitting of water
      into molecular hydrogen (H2) and oxygen (O2) using light involves two half
      reactions: the oxidation of water to O2 and the reduction of protons to H2. To
      take advantage of the full range of the solar spectrum, researchers have
      extensively investigated artificial photosynthesis systems consisting of two
      photosensitizers and two catalysts with a Z-configuration: one photosensitizer
      catalyst pair for H2 evolution and the other for O2 evolution. This type of
      complete artificial photosynthesis system is difficult to build and optimize;
      therefore, researchers typically study the reductive half-reaction and the
      oxidative half-reaction separately. To study the two half-reactions, researchers
      use a sacrificial electron donor to provide electrons for the reductive half
      reaction, and a sacrificial electron acceptor to capture electrons for the
      oxidative half-reaction. After optimization, they can eliminate the added donors
      and acceptors as the two half reactions are coupled to a complete photocatalytic
      water spitting system. Most photocatalytic systems for the H2 evolution half
      reaction consist of a photosensitizer, a catalyst, and a sacrificial electron
      donor. To promote photoinduced electron transfer and photocatalytic H2
      production, these three components should be assembled together in a controlled
      manner. Researchers have struggled to design a photocatalytic system for H2
      evolution that uses earth-abundant materials and is both efficient and durable.
      This Account reviews advances our laboratory has made in the development of new
      systems for photocatalytic H evolution that uses earth-abundant materials and is
      both efficient and durable. We used organometallic complexes and quantum-confined
      semiconductor nanocrystals (QDs) as photosensitizers, and [FeFe]-H2ase mimics and
      inorganic transition metal salts as catalysts to construct photocatalytic systems
      with sacrificial electron donors. Covalently linked Re(I) complex-[FeFe]-H2ase
      mimic dyads and ferrocene-Re(I) complex-[FeFe]-H2ase mimic triads could
      photocatalyze H2 production in organic solutions, but these photocatalytic
      systems tended to decompose. We also constructed several assemblies of CdTe and
      CdSe QDs as photosensitizers with [FeFe]-H2ase mimics as catalysts. These
      assemblies produced H2 in aqueous solutions photocatalytically and efficiently,
      with turnover numbers (TONs) up to tens of thousands. Assemblies of 3
      mercaptopropionic acid (MPA)-capped CdTe QDs with Co(2+) ions formed Coh-CdTe
      hollow nanospheres, and MPA capped-CdSe QDs with Ni(+) ions produced Nih-CdSe/CdS
      core/shell hybrids in situ in aqueous solutions upon irradiation. The resulting
      photocatalytic systems proved robust for H2 evolution. These systems showed
      excellent activity and impressive durability in the photocatalytic reaction,
      suggesting that they can serve as a valuable part of an overall water splitting
      system. 

PMID- 24873508
TI  - Dynamic supramolecular complexes constructed by orthogonal self-assembly.
AB  - CONSPECTUS: Supramolecular complexes, including various low-molecular-mass
      structures and large molecular aggregates that are assembled by reversible and
      highly directional noncovalent interactions, have attracted more and more
      attention due to their fascinating and unconventional chemical and physical
      properties that are different from those of traditional architectures encountered
      by covalently linked backbones. Supramolecular complexes are by nature dynamic
      architectures considering the reversibility of noncovalent interactions by which
      small molecular monomers can assemble into specific architectures that are able
      to be repeatably reorganized through the assembly/disassembly processes under
      certain environmental factors such as temperature, concentration, and solvent
      conditions. The construction of supramolecular complexes by orthogonal self
      assembly with different types of highly specific, noninterfering interactions is
      currently attracting considerable interest since they not only can dynamically
      self-assemble, but also can be tuned by various external stimuli through
      addressing each type of noncovalent interaction separately. Therefore, these
      dynamic supramolecular complexes, especially with external responsiveness,
      represent the most outstanding candidates for the future development of
      functional and smart materials, and even mimic the assembling process of natural
      systems. In this Account, we will summarize the recent advances of dynamic
      supramolecular complexes constructed by orthogonal self-assembly in soluiton in
      two sections: (1) Construction strategies for supramolecular complexes based on
      orthogonal self-assembly, whose dynamic behaviors with external responsiveness
      were not experimentally investigated but potentially existed due to the intrinsic
      reversibility of noncovalent bonds; (2) dynamic behaviors of multiresponsive
      supramolecular complexes, which were experimentally reported to exhibit
      reversible multi-responsiveness to external stimuli. Dynamic nature is one of
      intrinsic properties of supramolecular complexes constructed by self-assembly.
      Therefore, in the first section, we will describe the dynamic self-assembly in
      the construction of supramolecular complexes, but will focus on their external
      responsive dynamic behaviors in the second section. In addition, considering that
      an increasing number of supramolecular complexes constructed by biological
      building blocks through bio-orthogonal assembly as mimics of biological systems
      have been reported in recent years, in the second section we will also present
      some typical examples on such special dynamic biological supramolecular
      complexes. The final part of this Account is devoted to foreseeing the rapid
      development of dynamic supramolecular complexes toward applications in functional
      and smart materials and fundamental questions facing dynamic supramolecular
      complexes in the future.

PMID- 24873509
TI  - Simple capillary electrophoresis-mass spectrometry method for complex glycan
      analysis using a flow-through microvial interface.
AB  - A flow-through microvial is used to interface capillary electrophoresis and mass
      spectrometry (CE-MS) to develop a method for simultaneous profiling both neutral
      and sialylated glycans without derivatization or labeling. The CE separation was
      performed at near-zero electroosmotic flow in a capillary with neutral,
      hydrophilic coating, using 50 mM ammonium acetate in 20% methanol (pH 3.1) as the
      background electrolyte. The method was optimized with reversed CE polarity and
      negative ion ESI-MS. Enzymatically released N-glycans from human immunoglobulin G
      (IgG) were used as the test sample. The approach was also used to study the more
      complex N-glycans from recombinant human erythropoietin (rHuEPO) expressed in
      Chinese hamster ovary (CHO) cells. Glycoscreening of rHuEPO was performed using a
      triple quadrupole MS and an ultrahigh resolution TOF-MS. The high sensitivity and
      high mass accuracy of the TOF-MS revealed the presence of more than 70 glycans.
      Three mono- and di-sialylated tetra-antennary N-glycans and one mono-sialylated
      tri-antennary N-glycan of rHuEPO are reported for the first time. Further glycan
      heterogeneity was identified of the highly sialylated N-glycans of rHuEPO by
      extensive acetylation, Neu5Ac/Neu5Gc variation and the presence of N-acetyl
      lactosamine repeats. For comparative purposes, porous graphitic carbon-based LC
      MS/MS was also used to glycoprofile rHuEPO. This work demonstrates the potential
      of CE-MS to provide a comprehensive glycosylation profile with detailed features
      of the secondary glycan modifications. The CE-MS based method eliminates the need
      to label the N-glycans, as well as the requirement to desialylate before
      analysis, and could complement other established techniques for glycan
      characterization of therapeutic glycoproteins. 

PMID- 24873535
TI  - Self-assembly of Au nanoparticles on PMMA template as flexible, transparent, and
      highly active SERS substrates.
AB  - We report a simple and rapid method for fabricating a surface-enhanced Raman
      scattering (SERS) substrate, which offers good flexibility, excellent optical
      transparency, and high SERS activity. Specifically, the SERS substrate
      (AuNPs/PMMA film) was obtained through self-assembly of gold nanoparticles
      (AuNPs) on newborn poly(methyl methacrylate) (PMMA) template. The UV-vis
      spectroscopy analysis and scanning electron microscopy observation revealed that
      the gold nanoparticles were closely assembled on the flexible and transparent
      PMMA template. The fabricated AuNPs/PMMA film SERS substrate allowed detection of
      model molecule, malachite green isothiocyanate, at a concentration as low as 0.1
      nM, and exhibited good reproducibility in the SERS measurement. The Raman
      enhancement factor (EF) of the AuNPs/PMMA film was found to be as high as (2.4 +/
      0.3) * 10(7). In addition, measure of residual malachite green on fish surface
      was carried out, and the result indicated that the AuNPs/PMMA film had great
      potential in the in situ ultrasensitive detection of analyte on irregular
      objects. 

PMID- 24873526
TI  - Mass spectrometric detection of nanoparticle host-guest interactions in cells.
AB  - Synthetic host-guest chemistry is a versatile tool for biomedical applications.
      Characterization and detection of host-guest complexes in biological systems,
      however, is challenging due to the complexity of the biological milieu. Here, we
      describe and apply a mass spectrometric method to monitor the association and
      dissociation of nanoparticle (NP)-based host-guest interactions that integrates
      NP-assisted laser desorption/ionization (LDI) and matrix assisted laser
      desoption/ionization (MALDI) mass spectrometry. This LDI/MALDI approach reveals
      how NP surface functionality affects host-guest interactions in cells,
      information difficult to achieve using other techniques. 

PMID- 24873554
TI  - Aligned 1-D nanorods of a pi-gelator exhibit molecular orientation and excitation
      energy transport different from entangled fiber networks.
AB  - Linear pi-gelators self-assemble into entangled fibers in which the molecules are
      arranged perpendicular to the fiber long axis. However, orientation of gelator
      molecules in a direction parallel to the long axes of the one-dimensional (1-D)
      structures remains challenging. Herein we demonstrate that, at the air-water
      interface, an oligo(p-phenylenevinylene)-derived pi-gelator forms aligned
      nanorods of 340 +/- 120 nm length and 34 +/- 5 nm width, in which the gelator
      molecules are reoriented parallel to the long axis of the rods. The orientation
      change of the molecules results in distinct excited-state properties upon local
      photoexcitation, as evidenced by near-field scanning optical microscopy. A
      detailed understanding of the mechanism by which excitation energy migrates
      through these 1-D molecular assemblies might help in the design of supramolecular
      structures with improved charge-transport properties. 

PMID- 24873631
TI  - Bioaugmentation as a solution to increase methane production from an ammonia-rich
      substrate.
AB  - Ammonia-rich substrates inhibit the anaerobic digestion (AD) process and
      constitute the main reason for low energy recovery in full-scale reactors. It is
      estimated that many full-scale AD reactors are operating in ammonia induced
      "inhibited steady-state" with significant losses of the potential biogas
      production yield. To date there are not any reliable methods to alleviate the
      ammonia toxicity effect or to efficiently digest ammonia-rich waste. In the
      current study, bioaugmentation as a possible method to alleviate ammonia toxicity
      effect in a mesophilic continuously stirred-tank reactor (CSTR) operating under
      "inhibited steady state" was tested. A fast growing hydrogenotrophic methanogen
      (i.e., Methanoculleus bourgensis MS2(T)) was bioaugmented in the CSTR reactor at
      high ammonia levels (5 g NH4(+)-N L(-1)). A second CSTR reactor was used as
      control with no bioaugmentation. The results derived from this study clearly
      demonstrated a 31.3% increase in methane production yield in the CSTR reactor, at
      steady-state, after bioaugmentation. Additionally, high-throughput 16S rRNA gene
      sequencing analysis showed a 5-fold increase in relative abundance of
      Methanoculleus spp. after bioaugmentation. On the contrary to all methods used
      today to alleviate ammonia toxicity effect, the tested bioaugmentation process
      performed without interrupting the continuous operation of the reactor and
      without replacing the ammonia-rich feedstock. 

PMID- 24873648
TI  - Enantioselective total syntheses of FR901464 and spliceostatin A and evaluation
      of splicing activity of key derivatives.
AB  - FR901464 (1) and spliceostatin A (2) are potent inhibitors of spliceosomes. These
      compounds have shown remarkable anticancer activity against multiple human cancer
      cell lines. Herein, we describe efficient, enantioselective syntheses of
      FR901464, spliceostatin A, six corresponding diastereomers and an evaluation of
      their splicing activity. Syntheses of spliceostatin A and FR901464 were carried
      out in the longest linear sequence of 9 and 10 steps, respectively. To construct
      the highly functionalized tetrahydropyran A-ring, we utilized CBS reduction,
      Achmatowicz rearrangement, Michael addition, and reductive amination as key
      steps. The remarkable diastereoselectivity of the Michael addition was
      specifically demonstrated with different substrates under various reaction
      conditions. The side chain B was prepared from an optically active alcohol,
      followed by acetylation and hydrogenation over Lindlar's catalyst. The other
      densely functionalized tetrahydropyran C-ring was derived from readily available
      (R)-isopropylidene glyceraldehyde through a route featuring 1,2-addition, cyclic
      ketalization, and regioselective epoxidation. These fragments were coupled
      together at a late stage through amidation and cross-metathesis in a convergent
      manner. Six key diastereomers were then synthesized to probe the importance of
      specific stereochemical features of FR901464 and spliceostatin A, with respect to
      their in vitro splicing activity. 

PMID- 24873655
TI  - Sludge as a potential important source of antibiotic resistance genes in both the
      bacterial and bacteriophage fractions.
AB  - The emergence and prevalence of antibiotic resistance genes (ARGs) in the
      environment is a serious global health concern. ARGs found in bacteria can become
      mobilized in bacteriophage particles in the environment. Sludge derived from
      secondary treatment in wastewater treatment plants (WWTPs) constitutes a
      concentrated pool of bacteria and phages that are removed during the treatment
      process. This study evaluates the prevalence of ARGs in the bacterial and phage
      fractions of anaerobic digested sludge; five ARGs (blaTEM, blaCTX-M, qnrA, qnrS,
      and sul1) are quantified by qPCR. Comparison between the wastewater and sludge
      revealed a shift in the prevalence of ARGs (blaTEM and sul1 became more prevalent
      in sludge), suggesting there is a change in the bacterial and phage populations
      from wastewater to those selected during the secondary treatment and the later
      anaerobic mesophilic digestion of the sludge. ARGs densities were higher in the
      bacterial than in the phage fraction, with high densities in both fractions;
      particularly for blaTEM and sul1 (5 and 8 log10 gene copies (GC)/g, respectively,
      in bacterial DNA; 5.5 and 4.4 log10 GC/g, respectively, in phage DNA). These
      results question the potential agricultural uses of treated sludge, as it could
      contribute to the spread of ARGs in the environment and have an impact on the
      bacterial communities of the receiving ecosystem. 

PMID- 24873669
TI  - Effect of ginsenoside Rg1 on proliferation and neural phenotype differentiation
      of human adipose-derived stem cells in vitro.
AB  - AIMS: To investigate whether ginsenoside Rg1 can promote neural phenotype
      differentiation of human adipose-derived stem cells (hASCs) in vitro. METHODS:
      hASCs were isolated from lipo-aspirates, and characterized by specific cell
      markers and multilineage differentiation capacity after culturing to the 3rd
      passage. Cultured hASCs were treated with neural inductive media alone (group A,
      control) or inductive media plus 10, 50, or 100 MUg/mL ginsenoside Rg1 (groups B,
      C, and D, respectively). Cell proliferation was assessed by CCK-8 assay. Neuron
      specific enolase (NSE) and microtubule-associated protein-2 (MAP-2) levels were
      measured by Western blot. mRNA levels of growth associated protein-43 (GAP-43),
      neural cell adhesion molecule (NCAM), and synapsin-1 (SYN-1) were determined by
      real-time PCR. RESULTS: Ginsenoside Rg1 promoted the proliferation of hASCs
      (groups B, C, and D) and resulted in higher expression of NSE and MAP-2 compared
      with the control group. Gene expression levels of GAP-43, NCAM, and SYN-1 in the
      test groups were higher than that in thw control. The results displayed a dose
      dependent effect of ginsenoside Rg1 on cell proliferation and neural phenotype
      differentiation. CONCLUSION: This study indicated that ginsenoside Rg1 promotes
      cell proliferation and neural phenotype differentiation of hASCs in vitro,
      suggesting a potential use for hASCs in neural regeneration medicine.

PMID- 24873662
TI  - Induction of stemlike cells with fibrogenic properties by carbon nanotubes and
      its role in fibrogenesis.
AB  - We developed a three-dimensional fibroblastic nodule model for fibrogenicity
      testing of nanomaterials and investigated the role of fibroblast stemlike cells
      (FSCs) in the fibrogenic process. We showed that carbon nanotubes (CNTs) induced
      fibroblastic nodule formation in primary human lung fibroblast cultures
      resembling the fibroblastic foci in clinical fibrosis and promoted FSCs that are
      highly fibrogenic and a potential driving force of fibrogenesis. This study
      provides a predictive 3D model and mechanistic insight on CNT fibrogenesis. 

PMID- 24873675
TI  - Nutritional and nutraceutical quality of strawberries in relation to harvest time
      and crop conditions.
AB  - Three strawberry varieties cultivated in soilless systems were studied for their
      content of primary and secondary metabolites in relation to harvest time and crop
      conditions. The three varieties were chosen based on their sensitivity level to
      environmental stress: Palomar (very sensitive), Festival (sensitive), and
      Camarosa (resistant). Throughout the campaign, three samplings were performed:
      December (extra-early production), January, and March (early production).
      Differences among cultivars and harvest times were observed based on the contents
      of sugars, organic acids, phenolic compounds, and antioxidant capacity. The
      higher levels for total anthocyanins and flavan-3-ols were found in Camarosa and
      Festival strawberries, both in the January harvest. The Palomar variety showed
      higher total sugar/total organic acids ratio in the March harvest. The influence
      of cultivation practices and environmental conditions was assessed by nested
      ANOVA and PLS-DA. Differences in the sugar and phenolic content were observed
      depending upon variety and coverage type. TEAC was most influenced by the
      substrate type. 

PMID- 24873677
TI  - Potential targets in the discovery of new hair growth promoters for androgenic
      alopecia.
AB  - INTRODUCTION: Androgenic alopecia (AGA) is the major type of scalp hair loss
      affecting 60 - 70% of the population worldwide. It is caused by two potent
      androgens, namely testosterone (T) and 5alpha-dihydrotestosterone (5alpha-DHT).
      Till date, only two FDA-approved synthetic drugs, minoxidil and finasteride, are
      used to cure AGA with only 35 and 48% success, respectively; therefore, a search
      for new drug based on the mechanism of androgens action is still needed. AREAS
      COVERED: Relevant literature was reviewed to identify current therapeutic targets
      and treatments for AGA. The potential targets are classified into three
      categories: i) 5alpha-reductase; ii) androgen receptor and iii) growth-factor
      producing genes related to hair growth. EXPERT OPINION: Relevant assay systems
      using the right targets are required in order to obtain specific and effective
      drugs for AGA treatment. It is unlikely that single targeted agents will be
      sufficient for treating AGA, and therefore, it would be a challenge to obtain
      compounds with multiple activities.

PMID- 24873679
TI  - The needs of surgical training in the era of the European Working Time Directive.

PMID- 24873678
TI  - Acacia ferruginea inhibits cyclophosphamide-induced immunosuppression and
      urotoxicity by modulating cytokines in mice.
AB  - Cyclophosphamide (CTX), commonly used as an anti-neoplastic drug, can cause
      adverse side-effects including immunotoxicity and urotoxicity. Increasingly,
      plants have become sources of therapeutics that can help to restore host immunity
      to normal. In this study, Acacia ferruginea was assessed for an ability to
      protect mice against/mitigate CTX-induced toxicity. Co-administration of an
      extract of A. ferruginea (10 mg/kg BW, IP daily) for 10 consecutive days reduced
      CTX (25 mg/kg BW, IP daily)-induced toxicity. Apart from improvements in bladder
      and small intestine morphology, there was marked improvement in anti-oxidant
      (glutathione) levels in the bladder, suggesting a role for the anti-oxidant in
      reducing CTX-induced urotoxicity. Moreover, use of the extract significantly
      increased total leukocyte counts and bone marrow cellularity/alpha-esterase
      activity in CTX-treated mice which suggested a protective effect on the
      hematopoietic system. Co-treatment with the extract also prevented decreases in
      organ (liver, kidney, spleen, thymus) weight as well as body weight, thereby
      seemingly lessening the potential impact of CTX on the host immune system.
      Further, CTX-induced increases in serum aspartate transanimase, alanine
      transaminase, and alkaline phosphatase were reversed by extract co-treatment, as
      were alterations in in situ formation/release of interferon (IFN)-gamma,
      interleukin (IL)-2, granulocyte-macrophage colony stimulating factor (GM-CSF),
      and tumor necrosis factor (TNF)-alpha. Overall, this study indicated there were
      some protective effects from use of an extract of A. ferruginea against CTX
      induced toxicities, in part through modulation of levels of anti-oxidants and pro
      inflammatory cytokines.

PMID- 24873680
TI  - Panoptic, synoptic, and omnoptic surveillance.

PMID- 24873684
TI  - Importance of the autumn overturn and anoxic conditions in the hypolimnion for
      the annual methane emissions from a temperate lake.
AB  - Changes in the budget of dissolved methane measured in a small temperate lake
      over 1 year indicate that anoxic conditions in the hypolimnion and the autumn
      overturn period represent key factors for the overall annual methane emissions
      from lakes. During periods of stable stratification, large amounts of methane
      accumulate in anoxic deep waters. Approximately 46% of the stored methane was
      emitted during the autumn overturn, contributing ~80% of the annual diffusive
      methane emissions to the atmosphere. After the overturn period, the entire water
      column was oxic, and only 1% of the original quantity of methane remained in the
      water column. Current estimates of global methane emissions assume that all of
      the stored methane is released, whereas several studies of individual lakes have
      suggested that a major fraction of the stored methane is oxidized during
      overturns. Our results provide evidence that not all of the stored methane is
      released to the atmosphere during the overturn period. However, the fraction of
      stored methane emitted to the atmosphere during overturn may be substantially
      larger and the fraction of stored methane oxidized may be smaller than in the
      previous studies suggesting high oxidation losses of methane. The development or
      change in the vertical extent and duration of the anoxic hypolimnion, which can
      represent the main source of annual methane emissions from small lakes, may be an
      important aspect to consider for impact assessments of climate warming on the
      methane emissions from lakes. 

PMID- 24873685
TI  - Music causes deterioration of source memory: evidence from normal ageing.
AB  - Previous research has shown that music exposure can impair a wide variety of
      cognitive and behavioural performance. We investigated whether this is the case
      for source memory. Forty-one younger adults and 35 healthy elderly were required
      to retain the location in which pictures of coloured objects were displayed. On a
      subsequent recognition test they were required to decide whether the objects were
      displayed in the same location as before or not. Encoding took place (a) in
      silence, (b) while listening to street noise, or (c) while listening to Vivaldi's
      "Four Seasons". Recognition always took place during silence. A significant
      reduction in source memory was observed following music exposure, a reduction
      that was more pronounced for older adults than for younger adults. This pattern
      was significantly correlated with performance on an executive binding task. The
      exposure to music appeared to interfere with binding in working memory, worsening
      source recall. 

PMID- 24873686
TI  - Predicting return to work among sickness-certified patients in general practice:
      properties of two assessment tools.
AB  - AIM: The purpose was to analyse the properties of two models for the assessment
      of return to work after sickness certification, a manual one based on clinical
      judgement including non-measurable information ('gut feeling'), and a computer
      based one. STUDY POPULATION: All subjects aged 18 to 63 years, sickness-certified
      at a primary health care centre in Sweden during 8 months (n = 943), and followed
      up for 3 years. METHODS: Baseline information included age, sex, occupational
      status, sickness certification diagnosis, full-time or part-time current sick
      leave, and sick-leave days during the past year. Follow-up information included
      first and last day of each occurring sick spell. In the manual model all subjects
      were classified, based on baseline information and gut feeling, into a high-risk
      (n = 447) or a low-risk group (n = 496) regarding not returning to work when the
      present certificate expired. It was evaluated with a Cox's analysis, including
      time and return to work as dependent variables and risk group assignment as the
      independent variable, while in the computer-based model the baseline variables
      were entered as independent variables. RESULTS: Concordance between actual return
      to work and return to work predicted by the analysis model was 73%-76% during the
      first 28-180 days in the manual model, and approximately 10% units higher in the
      computer-based model. Based on the latter, three nomograms were constructed
      providing detailed information on the probability of return to work. CONCLUSION:
      The computer-based model had a higher precision and gave more detailed
      information than the manual model.

PMID- 24873688
TI  - Serotonin as a stimulator of hippocampal cell differentiation in tissue culture.
AB  - The effects of serotonin (5-HT) on morphofunctional development of hippocampal
      cultures derived from newborn rats were studied. It was established that
      systematic addition of 5-HT to nutrient medium during cultivation stimulates
      neuropil development, axon myelination and synaptogenesis. Electrophysiological
      studies of hippocampal cells in 5-HT treated cultures showed earlier exhibition
      of spontaneous activity and an increased number of spontaneously firing neurons
      and prevalence of periodic (bursting) type of discharges. These results indicate
      that 5-HT stimulates the differentiation of hippocampal cells in tissue culture. 

PMID- 24873687
TI  - Architectural and mechanical cues direct mesenchymal stem cell interactions with
      crosslinked gelatin scaffolds.
AB  - Naturally derived biomaterials have emerged as modulators of cell function and
      tissue substitutes. Here, we developed crosslinked glutaraldehyde (GTA) scaffolds
      for the expansion and differentiation of mesenchymal stem cells (MSCs). The
      mechanical and architectural properties of the scaffolds were altered by varying
      the concentration of gelatin and GTA. Higher GTA concentrations were associated
      with an increase in more confined pores and osteogenic differentiation. In
      addition, myogenic potential varied with crosslinking degree, although bulk
      mechanical properties were unaltered. Correlation analysis revealed that ALP
      activity of differentiated MSCs on higher gelatin concentration scaffolds was
      dependent on traditional effectors, including environment elasticity and spread
      area. In contrast, the differentiation capacity of cells cultured on lower
      gelatin concentration scaffolds did not correlate with these factors, instead it
      was dependent on the hydrated pore structure. These results suggest that scaffold
      composition can determine what factors direct differentiation and may have
      critical implications for biomaterial design. 

PMID- 24873689
TI  - Developing rat cerebellum: Glutamine and glutamate influx correlated to the
      cellular distribution of glutamine synthetase.
AB  - Glutamate has been suggested to be the neurotransmitter of the granule cells in
      cerebellar cortex. Autoradiographic studies using very low concentrations (1MUM
      range) of 2-3-[(3)H]l-glutamate or 2-3-[(3)H]l-glutamine have shown that both
      amino acids were preferentially taken up in the molecular layer of the cerebellar
      cortex of adult rats, but [(3)H]Glu accumulated essentially in glial cells, while
      Gln did not show a cellular preference (de Barry et al., Neuroscience 7,1289
      1297,1982). In this paper we show that during development the preferential
      accumulation of [(3)H]Glu and [(3)H]Gln are the same as in the adult but, in
      addition, at young ages (7-10 days) [(3)H]Gln accumulated in replicating cells of
      the external granular layer (EGL). The absence of glutamine synthetase in the EGL
      cells suggests that this accumulation of exogenous Gln might be used for the
      synthesis of purines and pyrimidines required for the active multiplication of
      these cells and is not correlated to neurotransmission. The metabolism of
      [(3)H]Gln was slow at young ages and changed during development. The metabolism
      of the Glu taken up was constant throughout development which is consistent with
      the hypothesis that high affinity Glu uptake is mainly a glial cell property and
      that the increasing accumulation rate during development reflects glial
      maturation. 

PMID- 24873690
TI  - Cerebrosides and their fatty acid profile in different regions of brains from
      small-for-date infants.
AB  - The concentration of cerebrosides and their fatty acid profile were determined in
      different regions of the brain, namely cerebrum, cerebellum and medulla
      oblongata, of normal infants (weighing > 2500 g) and of the two categories of
      small-for-date term infants (weighing 2000-2500 g and < 2000 g). Cerebroside
      concentration, in general, was observed to be low in the three regions of the
      brain from small-for-date infants. The magnitude of reduction varied with the
      region. The cerebrum, in particular, showed a significant reduction in the
      concentration of cerebrosides in the case of low-birth-weight infants. The
      nonhydroxy fatty acid distribution of cerebrosides indicated a lower proportion
      of long-chain fatty acids, namely lignoceric (24:0) and nervonic (24:1) acids, in
      the cerebellum and the medulla oblongata of small-for-date infants, and also in
      the cerebrum of those weighing < 2000 g. The observed changes in the
      concentration of cerebrosides and their fatty acid profile point to the
      possibility of impaired myelinization of the brain in small-for-date infants. 

PMID- 24873691
TI  - Transferrin in fetal rat brain and cerebrospinal fluid.
AB  - Concentrations of transferrin in plasma, cerebrospinal fluid (csf) and brain of
      fetal and newborn rats have been estimated by radial immunodiffusion assay.
      Transferrin was detected in both csf and brain at the earliest age investigated
      (12 days gestation). The plasma concentration increased throughout the
      gestational period studied and in the postnatal period: the overall increase was
      about 10-fold. In contrast, although the csf transferrin concentration increased
      by 3 times between 12 and 22 days (term) there was a considerable decline on
      reaching adult age. Brain transferrin concentration was highest at 18 days
      gestation. These results are important background information for studies of the
      significance of transferrin in brain development. 

PMID- 24873692
TI  - Effects of gangliosides on the in vitro development of neuroblastoma cells: An
      ultrastructural study.
AB  - The role of gangliosides in neuronal differentiation was studied by adding a
      mixture of bovine brain gangliosides to mouse neuroblastoma cells which were
      induced to differentiate through the application of gamma-aminobutyric acid
      (GABA) or sodium bromide (NaBr). GABA or NaBr was applied to 5-day-old cultures
      at concentrations ranging from 10(-4) to 10(-5)M. The cells were exposed to these
      substances over short periods of time (2 days). A mixture of bovine brain
      gangliosides was added to the 7-day-old cultures for 24-28 h. Electron microscopy
      revealed that ganglioside-induced morphological differentiation was accompanied
      by a significant number of mature synapse-like contacts. The GM1 gangliosides
      fraction apparently plays an important role in the formation of mature synapses,
      since none were observed when the GM1 was removed from the ganglioside mixture. 

PMID- 24873693
TI  - Distribution of the neural antigen BSP-2 in the cerebellum during development.
AB  - The monoclonal antibody anti-BSP-2 recognizes three glycosylated peptide chains
      of 180,000, 140,000 and 120,000 daltons in extracts from adult mouse forebrain
      and cerebellum. In extracts of embryonic or neonatal brain, it recognizes a
      different form, migrating as a broad band of higher molecular weight on SDS
      polyacrylamide gels. This report describes the distribution of the antigen BSP-2
      in developing mouse cerebella using a sensitive immunoperoxidase technique at the
      electron microscope level. As early as 3 days after birth the antigen can be
      detected on the surface of all cerebellar neurons, including neuroblasts in the
      external granular layer, basket and stellate neurons and Purkinje cells. In
      addition, radial glial fibres (astrocytes) terminating on the pial surface
      contain BSP-2. At later stages a pronounced surface labelling of parallel fibres
      is observed. Migrating granule cell perikaryal membranes possess the
      glycoprotein. The results are discussed in relation to the apparent identity of
      BSP-2 and the cell adhesion molecule N-CAM and its physiological properties. 

PMID- 24873694
TI  - Survival of chick embryo sympathetic neurons in cell culture.
AB  - Changes in neuronal numbers during the development of the chick embryo
      paravertebral sympathetic nervous system have been examined using cell culture
      techniques. Early sympathetic ganglia contain predominantly cells having neuronal
      phenotypes and these increase in number until embryonic day 9. Subsequently there
      is a large decrease in the number of neurons and an increase in the population of
      non-neuronal cells. This in vivo pattern is maintained when the neurons are grown
      in vitro, where Nerve Growth Factor more readily prevents the death of neurons
      cultured from 12-day or older embryos than those from earlier stages of
      development. 

PMID- 24873695
TI  - Immunohistochemical and biochemical approaches to the development of neuroglia in
      the CNS, with special reference to cerebellum.
AB  - Immunocytochemical methods have in recent years played a more important role in
      investigations of the development and function of glial cells in the nervous
      system because of their potential to distinguish between different cell
      populations. This short review attempts to highlight the value of this approach
      and summarizes the major cell-type markers currently available. These include,
      for the astrocyte, GFA protein, S-100 protein, vimentin, alphaalpha-enolase and
      alpha-2 glycoprotein. For the oligodendrocyte, myelin basic protein, the Wolfgram
      proteins, 2',3'-cyclic nucleotide 3'-phosphohydrolase, myelin associated
      glycoprotein, proteolipid protein, galactocerebroside, carbonic anhydrase and
      glycerol 3-phosphate dehydrogenase and other glial cell markers recognized by
      monoclonal antibodies are discussed. The application of these techniques to the
      study of the developing brain (and in particular the rodent cerebellum) are
      reviewed. It has proved possible to follow the development of distinct
      populations of astrocytes and oligodendrocytes from a very precocious age to the
      adult situation, thus providing new insight on the relationship between glial
      cells and neurons during normal and abnormal histogenesis. 

PMID- 24873697
TI  - Carbide-forming groups IVB-VIB metals: a new territory in the periodic table for
      CVD growth of graphene.
AB  - Early transition metals, especially groups IVB-VIB metals, can form stable
      carbides, which are known to exhibit excellent "noble-metal-like" catalytic
      activities. We demonstrate herein the applications of groups IVB-VIB metals in
      graphene growth using atmospheric pressure chemical vapor deposition technique.
      Similar to the extensively studied Cu, Ni, and noble metals, these transition
      metal foils facilitate the catalytic growth of single- to few-layer graphene. The
      most attractive advantage over the existing catalysts is their perfect control of
      layer thickness and uniformity with highly flexible experimental conditions by in
      situ converting the dissolved carbons into stable carbides to fully suppress the
      upward segregation/precipitation effect. The growth performance of graphene on
      these transition metals can be well explained by the periodic physicochemical
      properties of elements. Our work has disclosed a new territory of catalysts in
      the periodic table for graphene growth and is expected to trigger more interest
      in graphene research. 

PMID- 24873699
TI  - Influence of the selective EDTA derivative phenyldiaminetetraacetic acid on the
      speciation and extraction of heavy metals from a contaminated soil.
AB  - The development of more selective chelators for the washing of heavy metal
      contaminated soil is desirable in order to avoid excessive dissolution of soil
      minerals. Speciation and mobility of Cu, Zn, Pb, and Ni in a contaminated soil
      washed with phenyldiaminetetraacetic acid (PDTA), a derivative of EDTA, were
      investigated by batch leaching test using a range of soil washing conditions
      followed by sequential extraction. With appropriate washing conditions, PDTA
      significantly enhanced extraction of Cu from the contaminated soil. The primary
      mechanisms of Cu extraction by PDTA were complexation-promoted dissolution of
      soil Cu and increased dissolution of soil organic matter (SOM). PDTA showed high
      selectivity for Cu(II) over soil component cations (Ca(II), Mg(II), Fe(III),
      Mn(II), Al(III)), especially at lower liquid-to-soil ratios under PDTA
      deficiency, thus avoiding unwanted dissolution of soil minerals during the soil
      washing process which can degrade soil structure and interfere with future land
      use. PDTA-enhanced soil washing increased the exchangeable fractions of Cu, Zn,
      and Pb and decreased their residual fractions, compared to their levels in
      unwashed soil. 

PMID- 24873700
TI  - An efficient TiO2 coated immobilized system for the degradation studies of
      herbicide isoproturon: durability studies.
AB  - The investigation presents the observations on the use of cement beads for the
      immobilization of TiO2 for the degradation of herbicide isoproturon. The
      immobilized system was effective in degrading and mineralizing the herbicide for
      continuous thirty cycles without losing its durability. Catalyst was
      characterized by SEM-EDAX for checking the durability of the catalyst. The
      degradation rate followed first order kinetics as measured by change in
      absorption intensity in UV range as well as HPLC analysis. Two rounds of TiO2
      coating on inert cement beads with average diameter 1.5cm at UV Intensity 25Wm(
      2) calcined at 400 degrees C were the optimized conditions for the degradation of
      herbicide isoproturon. More than 90% TOC and COD reduction along with ammonium
      ions generation (80%) confirmed the mineralization of isoproturon. Fixed bed
      baffled reactor studies under solar irradiations using the TiO2 immobilized beads
      confirmed 85% degradation after 6h. LC-MS studies confirmed the intermediates
      formation and their subsequent degradation using immobilized system. 

PMID- 24873701
TI  - Increase of microbial growth potential in municipal secondary effluent by
      coagulation.
AB  - Microbial growth is a big issue of concern in the use of reclaimed water. In this
      study, the variation of microbial growth potentials of municipal secondary
      effluents after coagulation was evaluated by measuring assimilable organic carbon
      (AOC). Surprisingly, the AOC levels increased significantly (55-667%) after
      coagulation with poly-aluminum dosages of 60 mgL(-1) for the samples investigated
      in this research. By ultrafiltration membrane fractionation, the microbial growth
      potentials of the fractions with different molecular weight (MW) were measured.
      The results revealed that the maximum cell densities of microbial growth in
      secondary effluents were lower than those in their fractions with MW<10kDa.
      Meanwhile, the organic component with MW>10kDa in biological treated effluents
      was proved to have an inhibitory effect on microbial growth. Therefore, the
      removal of those high MW organic matters was the main reason for the increase of
      microbial growth potential in secondary effluents during coagulation.
      Furthermore, polysaccharides and/or proteins in secondary effluents were easily
      removed by coagulation and were thought to be the possible key organic substances
      affecting the microbial growth potential during coagulation. It is suggested that
      post treatments would be needed after coagulation to maintain the biological
      stability of reclaimed water.

PMID- 24873702
TI  - Selection of denitrifying phosphorous accumulating organisms in IFAS systems:
      comparison of nitrite with nitrate as an electron acceptor.
AB  - Nitrite and nitrate were compared as electron acceptors to select for
      denitrifying phosphorous accumulating organisms (DPAO) in two integrated fixed
      film activated sludge (IFAS 1 and IFAS 2) systems operated as sequencing batch
      reactors. The bench-scale experiment lasted one year and synthetic wastewater was
      used as feed. During anoxic conditions 20mgNO3(-)-NL(-1) were dosed into IFAS-1
      and 20mgNO2(-)-NL(-1) were dosed into IFAS-2. Long term phosphorous and ammonia
      removal via nitritation were achieved in both systems and both attached and
      suspended biomass contributed to phosphorous and ammonia removal. DPAO showed no
      specific adaptation to the electron acceptor as evidenced by short term switch of
      feeding with nitrate or nitrite. Anoxic phosphorus uptake rate was significantly
      higher with nitrite than with nitrate. Results showed that DPAO activity with
      nitrite could be integrated into attached and suspended biomass of IFAS systems
      in long term operation. 

PMID- 24873703
TI  - Decontamination of PCBs-containing soil using subcritical water extraction
      process.
AB  - Polychlorinated biphenyls (PCBs) are one of the excision compounds listed at the
      Stockholm convention in 2001. Although their use has been heavily restricted,
      PCBs can be found in some specific site-contaminated soils. Either removal or
      destruction is required prior to disposal. The subcritical water extraction
      (SCWE) of organic hazardous compounds from contaminated soils is a promising
      technique for hazardous waste contaminated-site cleanup. In this study, the
      removal of PCBs by the SCWE process was investigated. The effects of temperature
      and treatment time on removal efficiency have been determined. In the SCWE
      experiments, a removal percentage of 99.7% was obtained after 1h of treatment at
      250 degrees C. The mass removal efficiency of low-chlorinated species was higher
      than high-chlorinated congeners at lower temperatures, but it was oppositely
      observed at higher temperatures because the lower chlorinated congeners are
      formed by dechlorination of higher chlorinated congeners. Gas chromatography/mass
      spectrometry analysis confirmed that the PCBs underwent partial degradation.
      Several degradation products including mono- and di-chlorinated biphenyls, oxygen
      containing aromatic compounds, and small-size hydrocarbons were identified in the
      effluent water, which were not initially present in the contaminated soil. 

PMID- 24873704
TI  - Application of intensified Fenton oxidation to the treatment of sawmill
      wastewater.
AB  - The application of the Fenton process for the treatment of sawmill wastewater has
      been investigated. The sawmill wastewater was characterized by a moderate COD
      load (~3gL(-1)), high ecotoxicity (~ 40 toxicity units) and almost negligible
      BOD/COD ratio (5*10(-3)) due to the presence of different fungicides such as
      propiconazole and 3-iodo-2-propynyl butyl carbamate, being the wastewater
      classified as non-biodegradable. The effect of the key Fenton variables
      (temperature (50-120 degrees C), catalyst concentration (25-100 mg L(-1) Fe(3+)),
      H2O2 dose (1 and 2 times the stoichiometric dose) and the mode of H2O2 addition)
      on COD reduction and mineralization was investigated in order to fulfill the
      allowable local limits for industrial wastewater discharge and achieve an
      efficient consumption of H2O2 in short reaction times (1h). Increasing the
      temperature clearly improved the oxidation rate and mineralization degree,
      achieving 60% COD reduction and 50% mineralization at 120 degrees C after 1h with
      the stoichiometric H2O2 dose and 25 mg L(-1) Fe(3+). The distribution of H2O2 in
      multiple additions throughout the reaction time was clearly beneficial avoiding
      competitive scavenging reactions and thus, achieving higher efficiencies of H2O2
      consumption (XCOD ~ 80%). The main by-products were non-toxic short-chain organic
      acids (acetic, oxalic and formic). Thus, the application of the Fenton process
      allowed reaching the local limits for industrial wastewater discharge into local
      sewer system at a relatively low cost.

PMID- 24873705
TI  - Bioleaching characteristics, influencing factors of Cu solubilization and
      survival of Herbaspirillum sp. GW103 in Cu contaminated mine soil.
AB  - This study was aimed at assess the potential of diazotrophic bacteria,
      Herbaspirillum sp. GW103, for bioleaching of Cu in mine soil. The strain
      exhibited resistance to As (550mgL(-1)), Cu (350mgL(-1)), Zn (300mgL(-1)) and Pb
      (200mgL(-1)). The copper resistance was further confirmed by locating copA and
      copB genes. The survival of the isolate GW103 during bioleaching was analyzed
      using green fluorescent protein tagged GW103. Response surface methodology based
      Box-Behnken design was used to optimize the physical and chemical conditions for
      Cu bioleaching. Five significant variables (temperature, incubation time, CaCO3,
      coconut oil cake (COC), agitation rate) were selected for the optimization.
      Second-order polynomials were established to identify the relationship between Cu
      bioleaching and variables. The optimal conditions for maximum Cu bioleaching
      (66%) were 30 degrees C, 60h of incubation with 1.75% of CaCO3 and 3% COC at
      140rpm. The results of Cu sequential extraction studies indicated that the
      isolate GW103 leached Cu from ion-exchangeable, reducible, strong organic and
      residual fractions. Obtained results point out that the isolate GW103 could be
      used for bioleaching of Cu from mine soils. 

PMID- 24873706
TI  - Application of electrochemical advanced oxidation processes to the mineralization
      of the herbicide diuron.
AB  - Here, solutions with 0.185mM of the herbicide diuron of pH 3.0 have been treated
      by electrochemical advanced oxidation processes (EAOPs) like electrochemical
      oxidation with electrogenerated H2O2 (EO-H2O2), electro-Fenton (EF) and UVA
      photoelectro-Fenton (PEF) or solar PEF (SPEF). Trials were performed in stirred
      tank reactors of 100mL and in a recirculation flow plant of 2.5L using a filter
      press reactor with a Pt or boron-doped diamond (BDD) anode and an air-diffusion
      cathode for H2O2 electrogeneration. Oxidant hydroxyl radicals were formed from
      water oxidation at the anode and/or in the bulk from Fenton's reaction between
      added Fe(2+) and generated H2O2. In both systems, the relative oxidation ability
      of the EAOPs increased in the sequence EO-H2O2<EF<PEF or SPEF. The two latter
      processes were more powerful due to the photolysis of intermediates by UV
      radiation. In the stirred tank reactor, the PEF treatment with BDD was the most
      potent method, yielding 93% mineralization after 360 min at 100 mA cm(-2). In the
      flow plant, the SPEF process attained a maximum mineralization of 70% at 100 mA
      cm(-2). Lower current densities slightly reduced the mineralization degree in
      SPEF, enhancing the current efficiency and dropping the energy consumption. The
      diuron decay always obeyed a pseudo-first-order kinetics, with a much greater
      apparent rate constant in EF and SPEF compared to EO-H2O2. Oxalic and oxamic
      acids were detected as final carboxylic acids. Ammonium and chloride ions were
      also released, the latter ion being partially converted into chlorate and
      perchlorate ions at the BDD surface.

PMID- 24873707
TI  - Biological nutrient removal with low nitrous oxide generation by cancelling the
      anaerobic phase and extending the idle phase in a sequencing batch reactor.
AB  - Although wastewater biological nutrient removal can be achieved by alternating
      the anaerobic-oxic-anoxic phases, significant amount of nitrous oxide (N2O) is
      generated in oxic phases, where ammonia-oxidizing bacteria (AOB) rather than
      heterotrophic denitrifiers are the main contributors. Here a new efficient
      strategy to remarkably reduce N2O generation was reported. It was found that by
      cancelling the anaerobic phase and extending the idle phase the N2O generation
      was reduced by 42% using synthetic wastewater, whereas the total nitrogen and
      phosphorus removals were unaffected. The mechanistic investigations revealed that
      the cancelling of anaerobic phase benefited heterotrophic denitrifiers instead of
      AOB to be responsible for nitrogen removal in the oxic phases, increased the
      ratio of total nitrogen removal driven by external carbon source, and decreased
      nitrite accumulation. Quantitative real-time polymerase chain reaction and
      fluorescence in situ hybridization analyses further showed that the new strategy
      increased the number of N2O reducing bacteria but decreased the abundance of
      glycogen accumulating organisms, with N2O as their primary denitrification
      product. It was also determined that the ratio of nitric oxide reductase activity
      to N2O reductase activity was significantly decreased after anaerobic phase was
      cancelled. All these observations were in accord with the reduction of N2O
      production. The feasibility of this strategy to minimize the generation of N2O
      was finally confirmed for a real municipal wastewater. The results reported in
      this paper provide a new viewpoint to reduce N2O generation from wastewater
      biological nutrient removal. 

PMID- 24873708
TI  - GHG emissions during the high-rate production of compost using standard and
      advanced aeration strategies.
AB  - In this study, we have evaluated different strategies for the optimization of the
      aeration during the active thermophilic stage of the composting process of source
      selected Organic Fraction of Municipal Solid Waste (or biowaste) using reactors
      at bench scale (50L). These strategies include: typical cyclic aeration, oxygen
      feedback controller and a new self-developed controller based on the on-line
      maximization of the oxygen uptake rate (OUR) during the process. Results
      highlight differences found in the emission of most representative greenhouse
      gases (GHG) emitted from composting (methane and nitrous oxide) as well as in
      gases typically related to composting odor problems (ammonia as typical example).
      Specifically, the cyclic controller presents emissions that can double that of
      OUR controller, whereas oxygen feedback controller shows a better performance
      with respect to the cyclic controller. A new parameter, the respiration index
      efficiency, is presented to quantitatively evaluate the GHG emissions and, in
      consequence, the main negative environmental impact of the composting process.
      Other aspects such as the stability of the compost produced and the consumption
      of resources are also evaluated for each controller. 

PMID- 24873709
TI  - Ozonation of diesel-fuel contaminated sand and the implications for remediation
      end-points.
AB  - In this study, we investigate specifically the influence of soil grain size and
      water content on the degradation of n-alkane fractions and the formation of
      aldehydes and carboxylic acid during ozonation. 15 g of quartz sand spiked with
      diesel (25 g kg(-1)) were exposed to ozone for 20 h at concentrations of 10, 30
      and 50 mg L(-1), respectively. Results indicated that ozonation of the n-alkanes
      in fine grain size sand (0.15-0.25 mm) was 1.2 times faster than coarse sand due
      to higher surface contact area between O3 and sand particles. Soil moisture below
      18% w/w did not influence the ozonation efficiency. In contrast the ozonation led
      to an increase of acidity of the sand samples (pH=3.0) after 20 h treatment. This
      was due to the formation of carboxylic acid. Formaldehyde, one of the key by
      products of ozonation, was always <13 mg kg(-1) after the treatment which is
      below the industrial soil clean-up target level. While the aldehydes and
      carboxylic acid further reacted with O3 and their ozonation rate were slower than
      those of the alkanes suggesting that the hydroxylated by-products accumulated in
      the sand during the process. Overall the findings demonstrated that not only the
      alkanes but also aldehydes and carboxylic acid should be considered when defining
      remediation end-points.

PMID- 24873710
TI  - Efficacy of bioconversion of paper mill bamboo sludge and lime waste by
      composting and vermiconversion technologies.
AB  - Paper mill bamboo sludge (PMBS) and Paper mill lime waste (PMLW) are extensively
      produced as solid wastes in paper mills. Untreated PMBS and PMLW contain
      substantial amount of heavy metals (Zn, Pb, Ni, Cd, Cr) in soluble forms.
      Efficiency of vermiconversion and aerobic composting with these wastes is
      reported here. Adopted bioconversion systems enhanced the availability of some
      essential nutrients (N, P, K and Zn) in various combinations of cow dung (CD)
      with PMBS and PMLW. Colonization of nitrogen fixing bacteria and phosphate
      solubilizing bacteria considerably intensified under the vermiconversion system.
      Moreover, significant metal detoxification occurred due to vermiconversion.
      Various combinations of bioconverted PMBS and PMLW were applied to tissue
      cultured bamboo (Bambusa tulda) and chilli (Capsicum annum). Accelerated nutrient
      uptake coupled with improved soil quality resulted in significant production of
      chilli. Furthermore, vermiconverted PMBS+CD (1:1) and PMLW+CD (1:3) confirmed as
      potential enriching substrate for tissue cultured bamboo.

PMID- 24873711
TI  - Study of degradation intermediates formed during electrochemical oxidation of
      pesticide residue 2,6-dichlorobenzamide (BAM) at boron doped diamond (BDD) and
      platinum-iridium anodes.
AB  - Electrochemical oxidation is a promising technique for degradation of otherwise
      recalcitrant organic micropollutants in waters. In this study, the applicability
      of electrochemical oxidation was investigated concerning the degradation of the
      groundwater pollutant 2,6-dichlorobenzamide (BAM) through the electrochemical
      oxygen transfer process with two anode materials: Ti/Pt90-Ir10 and boron doped
      diamond (Si/BDD). Besides the efficiency of the degradation of the main
      pollutant, it is also of outmost importance to control the formation and fate of
      stable degradation intermediates. These were investigated quantitatively with
      HPLC-MS and TOC measurements and qualitatively with a combined HPLC-UV and HPLC
      MS protocol. 2,6-Dichlorobenzamide was found to be degraded most efficiently by
      the BDD cell, which also resulted in significantly lower amounts of intermediates
      formed during the process. The anodic degradation pathway was found to occur via
      substitution of hydroxyl groups until ring cleavage leading to carboxylic acids.
      For the BDD cell, there was a parallel cathodic degradation pathway that occurred
      via dechlorination. The combination of TOC with the combined HPLC-UV/MS was found
      to be a powerful method for determining the amount and nature of degradation
      intermediates. 

PMID- 24873712
TI  - Process controls for improving bioleaching performance of both Li and Co from
      spent lithium ion batteries at high pulp density and its thermodynamics and
      kinetics exploration.
AB  - Release of Co and Li from spent lithium ion batteries (LIBs) by bioleaching has
      attracted growing attentions. However, the pulp density was only 1% or lower,
      meaning that a huge quantity of media was required for bioleaching. In this work,
      bioleaching behavior of the spent LIBs at pulp densities ranging from 1% to 4%
      was investigated and process controls to improve bioleaching performance at pulp
      density of 2% were explored. The results showed that the pulp density exerted a
      considerable influence on leaching performance of Co and Li. The bioleaching
      efficiency decreased respectively from 52% to 10% for Co and from 80% to 37% for
      Li when pulp density rose from 1% to 4%. However, the maximum extraction
      efficiency of 89% for Li and 72% for Co was obtained at pulp density of 2% by
      process controls. Bioleaching of the spent LIBs has much greater potential to
      occur than traditional chemical leaching based on thermodynamics analysis. The
      product layer diffusion model described best bioleaching behavior of Co and Li. 

PMID- 24873713
TI  - Influence of particle size distribution, organic carbon, pH and chlorides on
      washing of mercury contaminated soil.
AB  - Feasibility of soil washing to remediate Hg contaminated soil was studied. Dry
      sieving was performed to evaluate Hg distribution in soil particle size
      fractions. The influence of dissolved organic matter and chlorides on Hg
      dissolution was assessed by batch leaching tests. Mercury mobilization in the pH
      range of 3-11 was studied by pH-static titration. Results showed infeasibility of
      physical separation via dry sieving, as the least contaminated fraction exceeded
      the Swedish generic guideline value for Hg in soils. Soluble Hg did not correlate
      with dissolved organic carbon in the water leachate. The highest Hg dissolution
      was achieved at pH 5 and 11, reaching up to 0.3% of the total Hg. The pH
      adjustment was therefore not sufficient for the Hg removal to acceptable levels.
      Chlorides did not facilitate Hg mobilization under acidic pH either. Mercury was
      firmly bound in the studied soil thus soil washing might be insufficient method
      to treat the studied soil. 

PMID- 24873714
TI  - Probing the radical chemistry in UV/persulfate-based saline wastewater treatment:
      kinetics modeling and byproducts identification.
AB  - The effect of Cl(-) on the oxidative degradation of Acid Orange 7 (AO7) was
      investigated in UV/S2O8(2-) system to elucidate the chlorination pathways in
      saline wastewaters. Lower amount of Cl(-) as well as Br(-) enhanced the
      decoloration of AO7, but such promotion effect reduced gradually with the
      increasing halide ion dosage. The dye mineralization was found to be inhibited by
      Cl(-), especially under acidic conditions. Results of kinetics modeling
      demonstrated that the fraction of different oxidizing radicals largely depended
      on the content of Cl(-). At the initial pH of 6.5, Cl2(-) was much more abundant
      than SO4(-). The significance of Cl2(-) for AO7 degradation increased with the
      increasing Cl(-) concentration and overwhelmed that of SO4(-) at [Cl(-)]>1mM.
      Without Cl(-), SO4(-) was the predominant radical for AO7 degradation under
      acidic conditions, while OH prevailed gradually at higher pH. Under high salinity
      conditions, more OH can be formed and contributed to the dye degradation
      especially in alkaline medium, leading to higher destruction efficiency of AO7.
      Several chlorinated byproducts were detected in the presence of chloride ions,
      and SO4(-)/Cl2(-)-based degradation pathways of AO7 were proposed. This work
      provides further understanding of the complex reaction mechanisms for SO4(-)
      based advanced oxidation processes in chloride-rich environments. 

PMID- 24873715
TI  - Integration of advanced oxidation processes at mild conditions in wet scrubbers
      for odourous sulphur compounds treatment.
AB  - The effectiveness of different advanced oxidation processes on the treatment of a
      multicomponent aqueous solution containing ethyl mercaptan, dimethyl sulphide and
      dimethyl disulphide (0.5 mg L(-1) of each sulphur compound) was investigated with
      the objective to assess which one is the most suitable treatment to be coupled in
      wet scrubbers used in odour treatment facilities. UV/H2O2, Fenton, photo-Fenton
      and ozone treatments were tested at mild conditions and the oxidation efficiency
      obtained was compared. The oxidation tests were carried out in magnetically
      stirred cylindrical quartz reactors using the same molar concentration of
      oxidants (hydrogen peroxide or ozone). The results show that ozone and photo
      Fenton are the most efficient treatments, achieving up to 95% of sulphur
      compounds oxidation and a mineralisation degree around 70% in 10 min.
      Furthermore, the total costs of the treatments taking into account the capital
      and operational costs were also estimated for a comparative purpose. The economic
      analysis revealed that the Fenton treatment is the most economical option to be
      integrated in a wet scrubber to remove volatile organic sulphur compounds, as
      long as there are no space constraints to install the required reactor volume. In
      the case of reactor volume limitation or retrofitting complexities, the ozone and
      photo-Fenton treatments should be considered as viable alternatives.

PMID- 24873717
TI  - Majority and minority gates realized in enzyme-biocatalyzed systems integrated
      with logic networks and interfaced with bioelectronic systems.
AB  - Biocatalytic reactions operating in parallel and resulting in reduction of NAD(+)
      or oxidation of NADH were used to mimic 3-input majority and minority logic
      gates, respectively. The substrates corresponding to the enzyme reactions were
      used as the input signals. When the input signals were applied at their high
      concentrations, defined as logic 1 input values, the corresponding biocatalytic
      reactions were activated, resulting in changes of the NADH concentration defined
      as the output signal. The NADH concentration changes were dependent on the number
      of parallel reactions activated by the input signals. The absence of the
      substrates, meaning their logic 0 input values, kept the reactions mute with no
      changes in the NADH concentration. In the system mimicking the majority function,
      the enzyme-biocatalyzed reactions resulted in a higher production of NADH when
      more than one input signal was applied at the logic 1 value. Another system
      mimicking the minority function consumed more NADH, thus leaving a smaller
      residual output signal, when more than one input signal was applied at the logic
      1 value. The performance of the majority gate was improved by processing the
      output signal through a filter system in which another biocatalytic reaction
      consumed a fraction of the output signal, thus reducing its physical value to
      zero when the logic 0 value was obtained. The majority gate was integrated with a
      preceding AND logic gate to illustrate the possibility of complex networks. The
      output signal, NADH, was also used to activate a process mimicking drug release,
      thus illustrating the use of the majority gate in decision-making biomedical
      systems. The 3-input majority gate was also used as a switchable AND/OR gate when
      one of the input signals was reserved as a command signal, switching the logic
      operation for processing of the other two inputs. Overall, the designed majority
      and minority logic gates demonstrate novel functions of biomolecular information
      processing systems. 

PMID- 24873721
TI  - When should neuroprotective drugs move from mice to men?

PMID- 24873722
TI  - Ontogeny of redox regulation in Atlantic cod (Gadus morhua) larvae.
AB  - The reduction potential of a cell is related to its fate. Proliferating cells are
      more reduced than those that are differentiating, whereas apoptotic cells are
      generally the most oxidized. Glutathione is considered the most important
      cellular redox buffer and the average reduction potential (Eh) of a cell or
      organism can be calculated from the concentrations of glutathione (GSH) and
      glutathione disulfide (GSSG). In this study, triplicate groups of cod larvae at
      various stages of development (3 to 63 days post-hatch; dph) were sampled for
      analyses of GSSG/2GSH concentrations, together with activities of antioxidant
      enzymes and expression of genes encoding proteins involved in redox metabolism.
      The concentration of total GSH (GSH+GSSG) increased from 610 +/- 100 to 1260 +/-
      150 MUmol/kg between 7 and 14 dph and was then constant until 49 dph, after which
      it decreased to 810 +/- 100 MUmol/kg by 63 dph. The 14- to 49-dph period, when
      total GSH concentrations were stable, coincides with the proposed period of
      metamorphosis in cod larvae. The concentration of GSSG comprised approximately 1%
      of the total GSH concentration and was stable throughout the sampling series.
      This resulted in a decreasing Eh from -239 +/- 1 to -262 +/- 7 mV between 7 and
      14 dph, after which it remained constant until 63 dph. The changes in GSH and Eh
      were accompanied by changes in the expression of several genes involved in redox
      balance and signaling, as well as changes in activities of antioxidant enzymes,
      with the most dynamic responses occurring in the early phase of cod larval
      development. It is hypothesized that metamorphosis in cod larvae starts with the
      onset of mosaic hyperplasia in the skeletal muscle at approximately 20 dph (6.8mm
      standard length (SL)) and ends with differentiation of the stomach and
      disappearance of the larval finfold at 40 to 50 dph (10-15 mm SL). Thus,
      metamorphosis in cod larvae seems to coincide with high and stable total
      concentrations of GSH.

PMID- 24873720
TI  - Davunetide in patients with progressive supranuclear palsy: a randomised, double
      blind, placebo-controlled phase 2/3 trial.
AB  - BACKGROUND: In preclinical studies, davunetide promoted microtubule stability and
      reduced tau phosphorylation. Because progressive supranuclear palsy (PSP) is
      linked to tau pathology, davunetide could be a treatment for PSP. We assessed the
      safety and efficacy of davunetide in patients with PSP. METHODS: In a double
      blind, parallel group, phase 2/3 trial, participants were randomly assigned with
      permuted blocks in a 1:1 ratio to davunetide (30 mg twice daily, intranasally) or
      placebo for 52 weeks at 48 centres in Australia, Canada, France, Germany, the UK,
      and the USA. Participants met the modified Neuroprotection and Natural History in
      Parkinson Plus Syndrome study criteria for PSP. Primary endpoints were the change
      from baseline in PSP Rating Scale (PSPRS) and Schwab and England Activities of
      Daily Living (SEADL) scale at up to 52 weeks. All participants and study
      personnel were masked to treatment assignment. Analysis was by intention to
      treat. The trial is registered with Clinicaltrials.gov, number NCT01110720.
      FINDINGS: 313 participants were randomly assigned to davunetide (n=157) or to
      placebo (n=156), and 241 (77%) completed the study (118 and 156 in the davunetide
      and placebo groups, respectively). There were no differences in the davunetide
      and placebo groups in the baseline PSPRS and SEADL. The davunetide and placebo
      groups did not differ in the change from baseline in PSPRS (median 11.8 [95% CI
      10.5 to 13.0] vs 11.8 [10.5 to 13.0], respectively, p=0.41) or SEADL (-0.20 [
      0.20 to -0.17] vs -0.20 [-0.22 to -0.17], respectively, p=0.92). 54 serious
      adverse events were reported in each of the treatment groups, including 11 deaths
      in the davunetide group and ten in the placebo group. The frequency of nasal
      adverse events was greater in the davunetide group than in the placebo group
      (epistaxis 18 [12%] of 156 vs 13 [8%] of 156, rhinorrhoea 15 [10%] vs eight [5%],
      and nasal discomfort 15 [10%] vs one [<1%]). INTERPRETATION: Davunetide is not an
      effective treatment for PSP. Clinical trials of disease-modifying treatment are
      feasible in patients with PSP and should be pursued with other promising tau
      directed treatments. FUNDING: Allon Therapeutics.

PMID- 24873723
TI  - Glutathione transferase omega 1 is required for the lipopolysaccharide-stimulated
      induction of NADPH oxidase 1 and the production of reactive oxygen species in
      macrophages.
AB  - Bacterial lipopolysaccharide (LPS) stimulation of macrophages and inflammation
      via the Toll-like receptor 4 (TLR4) signaling pathway through NF-kappaBeta
      generates reactive oxygen species (ROS) and proinflammatory cytokines such as IL
      1beta, IL-6, and TNFalpha. Because glutathione transferase Omega 1-1 (GSTO1-1)
      can catalyze redox reactions such as the deglutathionylation of proteins and has
      also been implicated in the release of IL-1beta we investigated its role in the
      development of LPS-mediated inflammation. Our data show that shRNA knockdown of
      GSTO1-1 in macrophage-like J774.1A cells blocks the expression of NADPH oxidase 1
      and the generation of ROS after LPS stimulation. Similar results were obtained
      with a GSTO1-1 inhibitor. To maintain high ROS levels during an inflammatory
      response, LPS stimulation causes the suppression of enzymes such as catalase and
      glutathione peroxidase that protect against oxidative stress. The knockdown of
      GSTO1-1 also attenuates this response. Our data indicate that GSTO1-1 needs to be
      catalytically active and mediates its effects on the LPS/TLR4 inflammatory
      pathway upstream of NF-kappaBeta. These data suggest that GSTO1-1 is a novel
      target for anti-inflammatory intervention. 

PMID- 24873725
TI  - Response to: Platelet indices in differential diagnosis of pancreatic
      neuroendocrine tumors from pancreatic adenocarcinomas.

PMID- 24873726
TI  - The importance of the costoclavicular space in upper limb primary deep vein
      thrombosis, a study with magnetic resonance imaging (MRI) technique enhanced by a
      blood pool agent.
AB  - BACKGROUND: Primary upper extremity deep vein thrombosis (UEDVT) can be divided
      into idiopathic and effort thrombosis. Anatomical factors probably play an
      important role in effort thrombosis, whereas the cause remains mostly unknown in
      idiopathic thrombosis. OBJECTIVES: The primary objective of this study was to
      examine the anatomy of the subclavian region and evaluate how these factors
      contribute to primary UEDVT. The secondary objective was to investigate if venous
      compression correlates with post thrombotic syndrome (PTS). PATIENTS AND METHODS:
      Fifteen patients and 15 controls were enrolled in the study. The subclavian
      region (the costoclavicular distance and vessel area) was examined by MRI
      enhanced by a blood-pool contrast agent (Vasovist). The MRI was performed in two
      arm positions: alongside and elevated. PTS and disability were quantified with
      the modified Villalta score and the Disability of the Arm, Shoulder and Hand
      (DASH) test. RESULTS: The costoclavicular distance was significantly narrower in
      the UEDVT patients with the arms alongside the body but there was a significant
      difference only in the left arm with the arms elevated. Area of the subclavian
      vein: When comparing the patients non-thrombotic arm with the controls, there was
      a significant difference only when the arms in the supine position. Disability:
      There was a high correlation between DASH, Villalta and VAS but no correlation
      between the MRI measurement and patient's symptoms or the Villalta Score.
      CONCLUSION: Our results suggest that primary UEDVT is dependent on the subclavian
      anatomy and area of vena subclavia.

PMID- 24873727
TI  - C9orf72; abnormal RNA expression is the key.
AB  - An expanded GGGGCC hexanucleotide repeat in the first intron located between the
      1st and 2nd non-coding exons of C9orf72 is the most frequent cause of
      frontotemporal dementia (FTD) and amyothropic lateral sclerosis (ALS). C9orf72 is
      a protein with largely unknown function and insight into the disease mechanism
      caused by the repeat expansion is still in an early stage but increases at an
      amazing pace. Three main hypotheses are currently being considered to explain the
      disease process including haploinsuffiency due to the loss of expression from the
      mutated allele, RNA toxicity caused by accumulation of repeat containing
      transcripts and toxic protein species generated by the abnormal translation of
      repeat sequences. We review the current status of genetic, population and
      functional data and discuss the current insights into the biology of C9orf72 and
      this repeat expansion disease. 

PMID- 24873728
TI  - Long-term survival, axonal growth-promotion, and myelination of Schwann cells
      grafted into contused spinal cord in adult rats.
AB  - Schwann cells (SCs) have been considered to be one of the most promising cell
      types for transplantation to treat spinal cord injury (SCI) due to their unique
      growth-promoting properties. Despite the extensive use as donor cells for
      transplantation in SCI models, the fate of SCs is controversial due in part to
      the lack of a reliable marker for tracing the grafted SCs. To precisely assess
      the fate and temporal profile of transplanted SCs, we isolated purified SCs from
      sciatic nerves of adult transgenic rats overexpressing GFP (SCs-GFP). SCs-GFP
      were directly injected into the epicenter of a moderate contusive SCI at the mid
      thoracic level at 1week post-injury. The number of SCs-GFP or SCs-GFP labeled
      with Bromodeoxyuridine (BrdU) was quantified at 5min, 1day, and 1, 2, 4, 12 and
      24weeks after cell injection. Basso, Beattie, and Bresnahan (BBB) locomotor
      rating scale, footfall error, thermal withdrawal latency, and footprint analysis
      were performed before and after the SCs-GFP transplantation. After
      transplantation, SCs-GFP quickly filled the lesion cavity. A remarkable survival
      of grafted SCs-GFP up to 24weeks post-grafting was observed with clearly
      identified SC individuals. SCs-GFP proliferated after injection, peaked at 2weeks
      (26% of total SCs-GFP), decreased thereafter, and ceased at 12weeks post
      grafting. Although grafted SCs-GFP were mainly confined within the border of
      surrounding host tissue, they migrated along the central canal for up to 5.0mm at
      4weeks post-grafting. Within the lesion site, grafted SCs-GFP myelinated
      regenerated axons and expressed protein zero (P0) and myelin basic protein (MBP).
      Within the SCs-GFP grafts, new blood vessels were formed. Except for a
      significant decrease of angle of rotation in the footprint analysis, we did not
      observe significant behavioral improvements in BBB locomotor rating scale,
      thermal withdrawal latency, or footfall errors, compared to the control animals
      that received no SCs-GFP. We conclude that SCs-GFP can survive remarkably well,
      proliferate, migrate along the central canal, and myelinate regenerated axons
      when being grafted into a clinically-relevant contusive SCI in adult rats.
      Combinatorial strategies, however, are essential to achieve a more meaningful
      functional regeneration of which SCs may play a significant role. 

PMID- 24873729
TI  - GABAB receptors in maintenance of neocortical circuit function.
AB  - Activation of metabotropic GABAB receptors (GABABRs) enhances tonic GABA current
      and substantially increases the frequency of spontaneous seizures. Despite the
      and pro-epileptic consequences of GABABR activation, mice lacking functional
      GABAB receptors (GABAB1R KO mice) exhibit clonic and rare absence seizures. To
      examine these mutant mice further, we recorded excitatory and inhibitory synaptic
      inputs and tonic mutant GABA currents from Layer 2 neocortical pyramidal neurons
      of GABAB1R WT and KO mice (P30-40). Tonic current was increased while the
      frequency of synaptic inputs was unchanged in KO mice relative to WT littermates.
      The neocortical laminar distribution of interneuron subtypes derived from the
      medial ganglionic eminence (MGE) was also not statistically different in KO mice
      relative to WT while the number of calretinin-positive, caudal GE-derived cells
      in Layer 1 was reduced. Transplantation of MGE progenitors obtained from KO mice
      lacking functional GABAB1R did not increase tonic inhibition in the host brain
      above that of media-injected controls. Taken together, these results suggest a
      complex role for GABAB receptors in mediating neocortical circuit function. 

PMID- 24873732
TI  - Improving work with fathers to prevent child maltreatment: fathers should be
      engaged as allies in child abuse and neglect prevention.

PMID- 24873730
TI  - Spatiotemporally limited BDNF and GDNF overexpression rescues motoneurons
      destined to die and induces elongative axon growth.
AB  - Axonal injury close to cell bodies of motoneurons induces the death of the vast
      majority of affected cells. Neurotrophic factors, such as brain derived
      neurotrophic factor (BDNF) and glial cell derived neurotrophic factor (GDNF),
      delivered close to the damaged motor pool in a non-regulated manner induce good
      survival of injured motoneurons and sprouting of their axons but fail to induce
      functional reinnervation. To avoid these drawbacks of high levels of neurotrophic
      expression, we devised an ex vivo gene therapy system to induce transient
      expression of BDNF/GDNF in transfected rat adipose tissue-derived stem cells
      (rASCs) which were grafted around the reimplanted ventral root, embedded in
      collagen gel. Strong BDNF/GDNF expression was induced in vitro in the first days
      after transfection with a significant decline in expression 10-14 days following
      transfection. Numerous axons of injured motoneurons were able to enter the
      reimplanted root following reimplantation and BDNF or GDNF treatment (192+/-17
      SEM vs 187+/-12 SEM, respectively) and produce morphological and functional
      reinnervation. Treatment with a combined cell population (BDNF+GDNF-transfected
      rASCs) induced slightly improved reinnervation (247+/-24 SEM). In contrast, only
      few motoneurons regenerated their axons in control animals (63+/-4 SEM) which
      received untransfected cells. The axons of surviving motoneurons showed
      elongative growth typical of regenerative axons, without aberrant growth or coil
      formation of sprouting axons. These findings provide evidence that damaged
      motoneurons require limited and spatially directed amounts of BDNF and GDNF to
      support their survival and regeneration. Moreover, neurotrophic support appears
      to be needed only for a critical period of time not longer than for two weeks
      after injury. 

PMID- 24873733
TI  - Exploring the Group B Streptococcus capsular polysaccharides: the structural
      diversity provides the basis for development of NMR-based identity assays.
AB  - Carbohydrate-based vaccines constitute a potent tool for prevention of life
      threatening bacterial infectious diseases like meningitis and pneumonia. Group B
      Streptococcus (GBS) is a major cause of neonatal sepsis and meningitis,
      particularly in infants born from mothers carrying the bacteria, and no vaccine
      is currently available. High-field Nuclear Magnetic Resonance (NMR) spectroscopy
      has been found to be an extremely robust tool for tracking the industrial process
      manufacturing of carbohydrate-based vaccines. Here we review the differences in
      the repeating unit structures of GBS capsular polysaccharide (CPS) type (Ia, Ib,
      II-VIII) yielding unique NMR proton profiles. All the profiles provided
      opportunities for selecting well resolved signals, in particular in the anomeric,
      the methylene protons at position C3 of N-acetyl-neuraminic acid (NeupNAc) and
      the N-Acetyl regions, which could be employed to develop an identity assay for
      monovalent vaccine bulks. Finally we reported a preliminary proof of concept of
      identity testing on a GBS CPS type Ia, Ib, III trivalent vaccine as blended
      bulks, based on the selection of one specific signal for each type in the
      anomeric region. 

PMID- 24873731
TI  - Global gene expression analysis following spinal cord injury in non-human
      primates.
AB  - Spinal cord injury (SCI) is a devastating condition with no established
      treatment. To better understand the pathology and develop a treatment modality
      for SCI, an understanding of the physiological changes following SCI at the
      molecular level is essential. However, studies on SCI have primarily used rodent
      models, and few studies have examined SCI in non-human primates. In this study,
      we analyzed the temporal changes in gene expression patterns following SCI in
      common marmosets (Callithrix jacchus) using microarray analysis and mRNA deep
      sequencing. This analysis revealed that, although the sequence of events is
      comparable between primates and rodents, the inflammatory response following SCI
      is significantly prolonged and the onset of glial scar formation is temporally
      delayed in primates compared with rodents. These observations indicate that the
      optimal time window to treat SCI significantly differs among different species.
      This study provides the first extensive analysis of gene expression following SCI
      in non-human primates and will serve as a valuable resource in understanding the
      pathology of SCI. 

PMID- 24873734
TI  - Analysis of niflumic acid prepared by rapid microwave-assisted evaporation.
AB  - Evaporative crystallization is widely applied in several industrial processes,
      including the pharmaceutical industry. Microwave irradiation can significantly
      speed up solvent evaporation in these crystallization processes, resulting in
      reduced particle size due to rapid crystallization. A single-mode microwave setup
      was used for evaporative crystallization of the model active pharmaceutical
      ingredient, niflumic acid, and the polymer, polyvinylpirrolidone (PVP).
      Production of crystals by microwave irradiation offers a modern way for drug
      formulation, and by reducing the particle size the dissolution rate and
      bioavailability of the active pharmaceutical ingredient can be enhanced. In this
      study, a 2.5-fold increase in the dissolution rate of the produced niflumic acid
      crystals was observed compared to the dissolution rate of the original drug in
      120min. When niflumic acid was produced together with the PVP in the microwave
      system, an amorphous solid dispersion was created with particles in the nano-size
      range, which showed a 5-fold increase in dissolution rate in 120min compared to
      the dissolution of the crystalline niflumic acid samples created by the microwave
      irradiation in the absence of PVP. 

PMID- 24873736
TI  - The role of familiarity in associative recognition of unitized compound word
      pairs.
AB  - This study examined the effect of unitization and contribution of familiarity in
      the recognition of word pairs. Compound words were presented as word pairs and
      were contrasted with noncompound word pairs in an associative recognition task.
      In Experiments 1 and 2, yes-no recognition hit and false-alarm rates were
      significantly higher for compound than for noncompound word pairs, with no
      difference in discrimination in both within- and between-subject comparisons.
      Experiment 2 also showed that item recognition was reduced for words from
      compound compared to noncompound word pairs, providing evidence of the
      unitization of the compound pairs. A two-alternative forced-choice test used in
      Experiments 3A and 3B provided evidence that the concordant effect for compound
      word pairs was largely due to familiarity. A discrimination advantage for
      compound word pairs was also seen in these experiments. Experiment 4A showed that
      a different pattern of results is seen when repeated noncompound word pairs are
      compared to compound word pairs. Experiment 4B showed that memory for the
      individual items of compound word pairs was impaired relative to items in
      repeated and nonrepeated noncompound word pairs, and Experiment 5 demonstrated
      that this effect is eliminated when the elements of compound word pairs are not
      unitized. The concordant pattern seen in yes-no recognition and the
      discrimination advantage in forced-choice recognition for compound relative to
      noncompound word pairs is due to greater reliance on familiarity at test when
      pairs are unitized. 

PMID- 24873737
TI  - Sins of omission: children selectively explore when teachers are under
      informative.
AB  - Do children know when people tell the truth but not the whole truth? Here we show
      that children accurately evaluate informants who omit information and adjust
      their exploratory behavior to compensate for under-informative pedagogy.
      Experiment 1 shows that given identical demonstrations of a toy, children (6- and
      7-year-olds) rate an informant lower if the toy also had non-demonstrated
      functions. Experiment 2 shows that given identical demonstrations, six-year-olds
      explore a toy more broadly if the informant previously committed a sin of
      omission. These results suggest that children consider both accuracy and
      informativeness in evaluating others' credibility and adjust their exploratory
      behavior to compensate for under-informative testimony when an informant's
      credibility is in doubt. 

PMID- 24873738
TI  - Mapping spatial frames of reference onto time: a review of theoretical accounts
      and empirical findings.
AB  - When speaking and reasoning about time, people around the world tend to do so
      with vocabulary and concepts borrowed from the domain of space. This raises the
      question of whether the cross-linguistic variability found for spatial
      representations, and the principles on which these are based, may also carry over
      to the domain of time. Real progress in addressing this question presupposes a
      taxonomy for the possible conceptualizations in one domain and its consistent and
      comprehensive mapping onto the other-a challenge that has been taken up only
      recently and is far from reaching consensus. This article aims at systematizing
      the theoretical and empirical advances in this field, with a focus on accounts
      that deal with frames of reference (FoRs). It reviews eight such accounts by
      identifying their conceptual ingredients and principles for space-time mapping,
      and it explores the potential for their integration. To evaluate their
      feasibility, data from some thirty empirical studies, conducted with speakers of
      sixteen different languages, are then scrutinized. This includes a critical
      assessment of the methods employed, a summary of the findings for each language
      group, and a (re-)analysis of the data in view of the theoretical questions. The
      discussion relates these findings to research on the mental time line, and
      explores the psychological reality of temporal FoRs, the degree of cross-domain
      consistency in FoR adoption, the role of deixis, and the sources and extent of
      space-time mapping more generally. 

PMID- 24873739
TI  - Characterisation of sphingolipids in the human lens by thin layer chromatography
      desorption electrospray ionisation mass spectrometry.
AB  - The lipidome of the human lens is unique in that cholesterol and
      dihydrosphingomyelin are the dominant classes. Moreover, the lens lipidome is not
      static with dramatic changes in several sphingolipid classes associated with both
      aging and cataract. Accordingly, there is a clear need to expand knowledge of the
      molecular species that constitute the human lens sphingolipidome. In this study,
      human lens lipids have been extracted and separated by thin-layer chromatography
      (TLC). Direct analysis of the TLC plates by desorption electrospray ionisation
      mass spectrometry (DESI-MS) allowed the detection over 30 species from 11 classes
      of sphingolipids. Significantly, novel classes of lens lipids including
      sulfatides, dihydrosulfatides, lactosylceramide sulfates and
      dihydrolactosylceramide sulfates were identified. 

PMID- 24873740
TI  - Commentary on "healthcare-associated infections after lower extremity
      revascularization".

PMID- 24873741
TI  - The effects of a nutrition education intervention on vending machine sales on a
      university campus.
AB  - OBJECTIVE: To determine the effects of a nutrition information intervention on
      the vending machine purchases on a college campus. PARTICIPANTS AND METHODS: Five
      high-use vending machines were selected for the intervention, which was conducted
      in the fall of 2011. Baseline sales data were collected in the 5 machines prior
      to the intervention. At the time of the intervention, color-coded stickers were
      placed near each item selection to identify less healthy (red), moderately
      healthy (yellow), and more healthy (green) snack items. Sales data were collected
      during the 2-week intervention. RESULTS: Purchases of red- and yellow-stickered
      foods were reduced in most of the machines; moreover, sales of the green
      stickered items increased in all of the machines. CONCLUSIONS: The increased
      purchases of healthier snack options demonstrate encouraging patterns that
      support more nutritious and healthy alternatives in vending machines.

PMID- 24873743
TI  - Quantitative analysis of alkaloidal constituents in imported fire ants by gas
      chromatography.
AB  - A method based on silica gel chromatography and GC-MS/GC-FID analyses was
      developed for the quantitation of alkaloidal compounds in imported fire ants,
      Solenopsis richteri, S. invicta, and their hybrid found in the southern United
      States. The cis and trans alkaloids from fire ant body extracts were successfully
      separated by silica gel chromatography, identified by GC-MS, and quantitated by
      GC-FID. Piperideine compounds were eluted together with the cis and trans
      piperidines, but were well-resolved on a nonpolar GC column. Eight pairs of
      piperidine isomers and 12 piperideines were quantitated. The ratios of trans
      alkaloids to corresponding cis isomers ranged from 87 to 378:1 in S. invicta and
      were significantly higher than in S. richteri and hybrid ants. The results were
      discussed in relation to the evolution of fire ant venom alkaloids and their role
      as host location cues for parasitic Pseudacteon phorid flies. 

PMID- 24873744
TI  - Immunomodulatory effects of clove (Syzygium aromaticum) constituents on
      macrophages: in vitro evaluations of aqueous and ethanolic components.
AB  - The present work sought to investigate potential suppressive effects on mouse
      macrophages by in vitro treatment with clove (Syzygium aromaticum) ethanolic
      extracted essential oil (containing eugenol) or its water-soluble extract. Using
      doses (ranging from 0.001-1000 ug/ml) of each material freshly prepared in the
      laboratory, cell survival and production of nitric oxide (NO), tumor necrosis
      factor (TNF)-alpha, interleukin (IL)-6, and IL-12 by the treated cells (that in
      all cases also had received LPS stimulation) were measured. Results indicated
      that, except at doses >=100 ug/ml, viability was unaffected in all groups. NO
      release by LPS-stimulated macrophages was generally significantly suppressed by
      either material; in contrast, low (i.e. 0.001-1 ug/ml) doses of either extract
      class appeared to enhance NO release by non-LPS (unstimulated)-treated
      macrophages. Among LPS-stimulated cells, TNFalpha release was also significantly
      affected by each extract; the ethanolic extract was suppressive at all doses
      tested, while the aqueous material was so up to 1 ug/ml and then became
      stimulatory. In contrast, nearly every dose of either extract appeared to
      stimulate IL-6 release from the LPS-treated cells. Effects on IL-12 production
      were overall inconsistent; in general, the ethanolic extract tended to be
      stimulatory of production by the LPS-treated cells. The data for the aqueous
      material showed no discernable pattern of effect. The results suggest that clove
      extracts do not have a distinct cytotoxic activity, but do impart potential anti-
      and pro-oxidant effects in cells, depending on their concentrations and on the
      activation state of the macrophages themselves at the time of exposure to the
      extracts. The impact of the extracts on macrophage cytokine release also displays
      a pattern of dose-relatedness.

PMID- 24873745
TI  - Efficient construction of unmarked recombinant mycobacteria using an improved
      system.
AB  - The genetic study of mycobacteria, such as Mycobacterium tuberculosis and
      Mycobacterium ulcerans, is hampered heavily by their slow growth. We have
      developed efficient, versatile, and improved genetic tools for constructing
      unmarked recombinant mycobacteria more rapidly including generating multiple
      mutants using the same antibiotic marker in both fast- and slow-growing
      mycobacteria. 

PMID- 24873749
TI  - Synergistic effects of Rhizoma Paridis and Rhizoma Curcuma longa on different
      animal tumor models.
AB  - Rhizoma Paridis saponins (RPS) with a good antitumor effect in clinical use
      showed low bioavailability and toxicity. Combination of Rhizoma Curcuma longa
      with RPS, which called LouHuang preparation (LH), not only overcame the RPS
      limitations but also improved its anticancer effect. The median lethal dose
      (LD50) of LH in mice was 3410.9 mg/kg by oral acute toxicity test. LH relieved
      the inhibition of RPS on the gastric emptying (70.13 +/- 4.80% vs. 49.12 +/-
      8.06%). As for the antitumor effect, the tumor weight/volume inhibition rate,
      tumor volume growth rate, and water/food efficiency ratio were calculated. LH had
      the highest inhibition ratio of 57.07 +/- 2.97% for H22 model, 43.22 +/- 0.72%
      for S180 model, and 46.8 +/- 0.97% for EAC model, which were higher than RPS.
      Compared to ZiLongJin (ZLJ), a marked antitumor drug in China, LH also had the
      higher inhibition rate for tumor weight and tumor volume growth, which weaker
      than CTX. The water/food efficiency ratio reflected the difference of the quality
      life of the mice bearing tumor cells or not. CTX attenuated body weight gain and
      increased food efficiency ratio compared to control group. LH did not affect the
      body weight or water/food intake. The active part of LH was RPS and turmeric
      polysaccharides with the inhibition of 58% and 47% on H22 and S180 tumor models.
      The research provided theoretical and practical basis for LH application.

PMID- 24873750
TI  - One-pot synthesis of a 3,6-branched hexaarabinogalactan using galactopyranosyl
      thioglycoside diol as a key glycosylating agent.
AB  - We present in this paper the efficient four-component one-pot synthesis of a
      fully protected hexaarabinogalactan 2 with di-branched structure by using D
      thiogalactopyranoside 3,6-diol 3 as the central glycosylating agent. After global
      deprotection, 2 was converted into the 3-aminopropyl linker-containing free
      oligosaccharide 1 that is structurally related to ALR-5IIa-1-1, an arabino-3,6
      galactan with intestinal immune system modulating activity.

PMID- 24873752
TI  - GPs in England prescribed 2.7 million extra antidepressants during 2012
      recession.

PMID- 24873754
TI  - Global perspective on the oxidative potential of airborne particulate matter: a
      synthesis of research findings.
AB  - An emerging hypothesis in the field of air pollution is that oxidative stress is
      one of the important pathways leading to adverse health effects of airborne
      particulate matter (PM). To advance our understanding of sources and chemical
      elements contributing to aerosol oxidative potential and provide global
      comparative data, we report here on the biological oxidative potential associated
      with size-segregated airborne PM in different urban areas of the world, measured
      by a biological (cell-based) reactive oxygen species (ROS) assay. Our synthesis
      indicates a generally greater intrinsic PM oxidative potential as well as higher
      levels of exposure to redox-active PM in developing areas of the world. Moreover,
      on the basis of our observations, smaller size fractions are generally associated
      with higher intrinsic ROS activity compared with larger PM size fractions.
      Another important outcome of our study is the identification of major species and
      sources that are associated with ROS activity. Water-soluble transition metals
      (e.g., Fe, Ni, Cu, Cr, Mn, Zn and V) and water-soluble organic carbon (WSOC)
      showed consistent correlations with the oxidative potential of airborne PM across
      different urban areas and size ranges. The major PM sources associated with these
      chemical species include residual/fuel oil combustion, traffic emissions, and
      secondary organic aerosol formation, indicating that these sources are major
      drivers of PM-induced oxidative potential. Moreover, comparison of ROS activity
      levels across different seasons indicated that photochemical aging increases the
      intrinsic oxidative potential of airborne PM. 

PMID- 24873758
TI  - The buccal mucosa as a route for TiO2 nanoparticle uptake.
AB  - The oral cavity, although part of the aero-digestive tract, is still neglected in
      terms of risk assessment with respect to nanoparticle uptake. If nanoparticles
      enter the oral cavity, either via oral products or inhaled materials, it is not
      clear whether they rapidly interact with the mucosae or are swallowed. In this
      study, interactions of three distinct titanium dioxide (TiO2) particles (i.e. NM
      100, NM 101 and NM 105) with oral tissues are presented. Physicochemical
      properties were addressed in relevant media, and particle penetration was
      investigated with an ex vivo model using porcine mucosa. To avoid modification of
      the particle surfaces via labeling, multiphoton microscopy was introduced as an
      accurate method to detect TiO2 particles within the tissue. The spatiotemporal
      aspects of nanoparticle uptake, as well as the intracellular localization in
      human epithelial cells, were studied and potential toxic effects were evaluated.
      Although TiO2 particles formed large aggregates once dispersed in media, 10-50%
      remained in the nanoscale range, rapidly interacting with the mucus layer and
      infecting the epithelium. However, differences in the penetration depth were
      observed depending on the particle characteristics. NM 100 and NM 105 were found
      in both the upper part and the lower part of the buccal mucosa, while NM 101
      (smallest particle sizes) only penetrated the upper parts. Transport studies
      revealed that TiO2 nanoparticles were found in vesicles, as well as freely
      distributed in the cytoplasm. Cell viability/integrity was not affected
      negatively; however, NM 105 triggered the production of reactive oxygen species.
      These data clearly suggest that the oral cavity should be considered in further
      risk assessment studies. 

PMID- 24873753
TI  - Driving cartilage formation in high-density human adipose-derived stem cell
      aggregate and sheet constructs without exogenous growth factor delivery.
AB  - An attractive cell source for cartilage tissue engineering, human adipose-derived
      stem cells (hASCs) can be easily expanded and signaled to differentiate into
      chondrocytes. This study explores the influence of growth factor distribution and
      release kinetics on cartilage formation within 3D hASC constructs incorporated
      with transforming growth factor-beta1 (TGF-beta1)-loaded gelatin microspheres.
      The amounts of microspheres, TGF-beta1 concentration, and polymer degradation
      rate were varied within hASC aggregates. Microsphere and TGF-beta1 loading
      concentrations were identified that resulted in glycosaminoglycan (GAG)
      production comparable to those of control aggregates cultured in TGF-beta1
      containing medium. Self-assembling hASC sheets were then engineered for the
      production of larger, more clinically relevant constructs. Chondrogenesis was
      observed in hASC-only sheets cultured with exogenous TGF-beta1 at 3 weeks.
      Importantly, sheets with incorporated TGF-beta1-loaded microspheres achieved GAG
      production similar to sheets treated with exogenous TGF-beta1. Cartilage
      formation was confirmed histologically via observation of cartilage-like
      morphology and GAG staining. This is the first demonstration of the self-assembly
      of hASCs into high-density cell sheets capable of forming cartilage in the
      presence of exogenous TGF-beta1 or with TGF-beta1-releasing microspheres.
      Microsphere incorporation may bypass the need for extended in vitro culture,
      potentially enabling hASC sheets to be implanted more rapidly into defects to
      regenerate cartilage in vivo. 

PMID- 24873759
TI  - Identifying contact-mediated, localized toxic effects of MWCNT aggregates on
      epithelial monolayers: a single-cell monitoring toxicity assay.
AB  - Aggregates of multiwalled carbon nanotubes (MWCNT) impair the barrier properties
      of human airway cell monolayers. To resolve the mechanism of the barrier
      alteration, monolayers of Calu-3 human airway epithelial cells were exposed to
      aggregated MWCNT. At the cell-population level, trans-epithelial electrical
      resistance (TEER) was used as an indicator of barrier competence, caspase
      activity was assessed with standard biochemical assays, and cell viability was
      investigated by biochemical techniques and high-throughput screening (HTS)
      technique based on automated epifluorescence microscopy. At cell level, the
      response to MWCNT was investigated with confocal microscopy, by evaluating cell
      death (calcein/propidium iodide (PI)), proliferation (Ki-67), and apoptosis
      (caspase activity). At the cell-population level, exposure to aggregated MWCNT
      caused a decrease in TEER, which was not associated with a decrease in cell
      viability or onset of apoptosis even after an 8-d exposure. In contrast, confocal
      imaging demonstrated contact with MWCNT aggregates triggered cell death after 24
      h of exposure. In the presence of a natural surfactant, both TEER decrease and
      contact-mediated toxicity were mitigated. With confocal imaging, increased
      proliferation and apoptosis were detected in Calu-3 cells next to the aggregates.
      Contact-mediated cytotoxicity was recorded in two additional cell lines (BEAS-2B
      and A549) derived from human airways. Similar results were confirmed by adopting
      two additional MWCNT preparations with different physico-chemical features. This
      indicates MWCNT caused localized damage to airway epithelial monolayers in vitro
      and altered the apoptotic and proliferative rate of epithelial cells in close
      proximity to the aggregates. These findings provide evidence on the pathway by
      which MWCNT aggregates impair airway barrier function, and support the use of
      imaging techniques as a possible regulatory-decision supporting tool to identify
      effects of aggregated nanomaterials not readily detected at cell population
      level.

PMID- 24873761
TI  - Trifluoroethanethiol: an additive for efficient one-pot peptide ligation
      desulfurization chemistry.
AB  - Native chemical ligation followed by desulfurization is a powerful strategy for
      the assembly of proteins. Here we describe the development of a high-yielding,
      one-pot ligation-desulfurization protocol that uses trifluoroethanethiol (TFET)
      as a novel thiol additive. The synthetic utility of this TFET-enabled methodology
      is demonstrated by the efficient multi-step one-pot syntheses of two tick-derived
      proteins, chimadanin and madanin-1, without the need for any intermediary
      purification. 

PMID- 24873760
TI  - Exercise and vascular function: how much is too much?
AB  - Exercise is a powerful therapy for preventing the onset of and slowing the
      progression of cardiovascular disease. Increased shear stress during exercise
      improves vascular homeostasis by both decreasing reactive oxygen species and
      increasing nitric oxide bioavailability in the endothelium. While these
      observations are well accepted as they apply to individuals at risk for
      cardiovascular disease, less is known about how exercise, especially intense
      exercise, affects vascular function in healthy individuals. This review
      highlights examples of how vascular function can paradoxically be impaired in
      otherwise healthy individuals by extreme levels of exercise, with a focus on the
      causative role that reactive oxygen species play in this impairment. 

PMID- 24873762
TI  - [Attila Voros, professor of surgery -- congratulations on his 70. birthday].

PMID- 24873763
TI  - [Surgical management of non-palpable breast tumors].
AB  - Due to the improvement of the diagnostic and screening methods for detecting
      breast cancer (e.g. mammography, breast ultrasonography, MR imaging, FNAC, core
      biopsy or vacuum-assisted core biopsy), non-palpable breast masses are more and
      more commonly discovered. Resection guided by a radiologically placed hookwire
      has gained outstanding importance in the surgical management of these non
      palpable cases of breast malformations. In this retrospective study we analyzed
      the data of 830 patients operated in the past 5 years because of breast
      malformations. Of those, 36.9% of the breast surgeries were performed because of
      a non-palpable breast mass. In such cases we performed preoperative histological
      sampling to support setting up the surgical plan. We managed to get a precise
      histological diagnosis preoperatively in 78% of our cases. After the introduction
      of vacuum-assisted core biopsy, operations for histologically indeterminate
      breast tumors became less common. The surgical resections of breast masses which
      later prove to be benign are expected to decrease further. Intraoperative
      radiological analysis of the resection margins helps performing a definitive
      surgical resection. Specimen mammography and ultrasonography is part of our daily
      routine. When evaluating the histological samples, the question of resection
      margins is substantial. In absence of clear resection margins, re-resection is
      needed. Due to incomplete resection margins 5.5% of the cases re-resection was
      needed. To avoid unnecessary axillary lymph node dissection in case of early
      stage breast cancers, sentinel lymph node biopsy is always carried out. 

PMID- 24873764
TI  - [Urgent laparoscopic adrenalectomy in acute crisis caused by pheochromocytoma].
AB  - CASE REPORT: Authors present the case of a 30-year-old female patient, who was
      admitted to the ICU because of hypertensive crisis accompanied by chest
      complains, cardiac decompensation, progrediating short of breath and
      unconsciousness. Despite the quick examinations and the prompt treatment multi
      organ failure developed 3 days after admission. Investigations revealed the
      underlying cause, which was a left-sided suprarenal neoplasm. Hence,
      multidisciplinary decision was made to carry out a laparoscopic adrenalectomy
      urgently. The histology examination of the removed neoplasm was pheochromocytoma.
      In the postoperative period the condition of the patient gradually improved, her
      symptoms and complains settled, and finally she was discharged in a healthy
      condition. DISCUSSION: The diagnosis of a pheochromocytoma is a difficult task,
      the symptoms and complains caused by it can simulate many other illnesses. The
      acute crisis caused by pheochromocytoma usually can be treated conservatively,
      but in more severe cases with impending multi-organ failure an urgent operative
      treatment can be unavoidable. Though the operative risk is relatively high, the
      correct intra- and postoperative treatment with a quick laparoscopic procedure
      can be effective.

PMID- 24873765
TI  - [Laparoscopic treatment of median arcuate ligament syndrome (MALS) -- case
      report].
AB  - CASE REPORT: The authors report a case of a 34-year-old woman who had
      postprandial abdominal pain for years. During the course of her examination
      lactose intolerance and hiatus hernia was diagnosed. After ineffective
      conservative treatment CT angiography (CTA) and digital substraction angiography
      (DSA) was performed and showed significant celiac artery stenosis. Percutaneous
      transluminal angioplasty (PTA) was unsuccessful as extravasal mechanical
      compression was present, therefore, laparoscopic decompression and surgical
      division of MAL fibres were carried out. The postoperative period was
      characterized by a complete relief of previous symptoms and repeated CTA showed
      normal blood flow. DISCUSSION: The authors emphasize the importance of the
      measurement of peak velocity of celiac trunk with Colour Duplex abdominal
      ultrasonography, the examination has 100% sensitivity and 83% specificity. The
      Duplex ultrasonography is less expensive than the "gold standard" diagnostic
      methods like CT and DS angiography, and can lead us to early diagnosis.
      Laparoscopic surgery is safe and low expense method for celiac artery
      decompression, however, sometimes it is difficult to reveal the exact reason and
      thus setting up the proper operation plan.

PMID- 24873766
TI  - [Analysis of postoperative complications following acute surgery for colorectal
      cancer].
AB  - Our aim was to improve the outcome of emergency surgeries for colorectal cancer
      (CRC). Authors compared two periods: 2004-2006 and 2007-2011. Targeted cases were
      emergency admissions, in which the diagnosis of colorectal cancer is only
      revealed during work-up or during surgery. No other exclusion criteria were set.
      Analyzed main endpoints were anastomotic leak, postoperative mortality,
      resecability. ASA classification and TNM stages were assessed in order to learn
      morbidity and general condition prior to acute surgery. Considering the
      experience gained in prior period, in 2007, authors have made a change in
      treatment strategy. In following years leakage ratio became ten times lower and
      mortality was reduced by 5%. There is a great chance that fast work-up and
      preparation for surgery may decrease complications and mortality. The aim would
      be for CRC patients, is to reach surgery in an early stage of disease as
      possible, at least before complications develop. 

PMID- 24873768
TI  - [Metastatic malignant melanoma of the oesophagus: case report].
AB  - We report a case of metastatic malignant melanoma in the oesophagus. 13 years
      after the wide excision of primary skin melanoma, we found a polypoid tumor in
      the upper third of the oesophagus. Biopsy result was melanoma malignum. After
      negative staging we performed transhiatal oesophagectomy with gastric conduit and
      cervical anastomosis. Metastatic nature of the oesophageal tumor was proven by
      histology. After uneventful postoperative course, the patient received adjuvant
      dacarbazine treatment. The patient was is in good condition, and disease free on
      the 18 month follow-up. 

PMID- 24873767
TI  - [Our experience in Fournier's gangrene with severe septic shock].
AB  - Fournier's gangrene is a rare, rapidly progressing necrotizing fasciitis, which
      involves the genital area and perineum, progresses towards the thighs and
      abdominal wall through fascial plains. In our surgical department we treated
      seven patients with Fournier's gangrene between 2007 and 2011. Early diagnosis,
      immediate radical surgical debridement, necrosectomy, appropriate antibiotics and
      intensive care are all required and necessary for the successful treatment.
      Despite appropriate therapy, two patients were lost in septic shock. 

PMID- 24873769
TI  - [Our experience with totally extraperitoneal technique of laparoscopic inguinal
      hernia repairs modified by Stolzenburg].
AB  - INTRODUCTION: Two current types of laparoscopic inguinal hernia repair are known:
      the TransAbdominal PrePeritoneal (TAPP) and the Totally ExtraPeritoneal (TEP)
      method. The mesh is placed in the preperitoneal space (sublay). Usually during
      TAPP method we fix the mesh with tacks or staples. In case of TEP fixation it is
      not necessary because the intraabdominal pressure keeps the implant in position.
      There is no significant difference between the two methods in terms of
      recurrence. The advantage of TEP is that the abdominal cavity remains intact,
      hence reduces the risk of intraabdominal injuries and adhesions. It is
      unnecessary to use special stapler or tacker. MATERIALS AND METHODS: Our team
      performed 50 TEP procedures in male patients with uni- or bilateral inguinal
      hernias in the period 2011-2013. We prepared the mesh in a special way according
      to Stolzenburg and placed it to the subfunicular area. We did not apply
      additional fixation (tacks, stitches) and drainage. Mean hospital stay was 1 day.
      We allowed complete physical activity 10-12 days after surgery. RESULTS: No
      recurrence was observed during the 2 years of follow-up. The mean operating time
      was 70 minutes. We performed conversion in 3 cases (Lichtenstein 2, TAPP 1). In
      one case there was an injury of the inferior epigastric artery. In two cases we
      have detected neuralgia in the postoperative period. CONCLUSIONS: After the
      learning curve the TEP method can be used safely with good functional results.
      The technique of mesh positioning reduces the risk of complications and provides
      cost-effectiveness.

PMID- 24873770
TI  - [Necrotizing enterocolitis in an adult -- case report].
AB  - The adult necrotizing enterocolitis (ANEC) is a rare condition, frequently fatal,
      and characterized by a fulminant symptoms and segmental necrosis of the bowel.
      The authors performed repeated surgeries and small bowel resections on a patient
      classified to stage number three on Bell scale due to necrotizing enterocolitis.
      Pathological examination of the resected bowel showed intestinal necrosis without
      obstruction of mesenteric vessels. After the fifth operation the continuity of
      the gastrointestinal tract was reconstructed by an anastomosis between the
      remained 30 cm of terminal ileum and descending loop of duodenum. Inspite of only
      30 cm of small intestines remaining, the patient is able to enjoy life almost
      completely with gastroenterological control and support.

PMID- 24873771
TI  - [A few more thoughts regarding the history of the sentinel lymph node in Pecs,
      Hungary].

PMID- 24873772
TI  - [Abstract of the 62nd Congress of the Hungarian Surgical Society, June 12-14,
      2014, Gyor, Hungary].

PMID- 24873775
TI  - High density catalytic hot spots in ultrafine wavy nanowires.
AB  - Structural defects/grain boundaries in metallic materials can exhibit unusual
      chemical reactivity and play important roles in catalysis. Bulk polycrystalline
      materials possess many structural defects, which is, however, usually
      inaccessible to solution reactants and hardly useful for practical catalytic
      reactions. Typical metallic nanocrystals usually exhibit well-defined crystalline
      structure with few defects/grain boundaries. Here, we report the design of
      ultrafine wavy nanowires (WNWs) with a high density of accessible structural
      defects/grain boundaries as highly active catalytic hot spots. We show that
      rhodium WNWs can be readily synthesized with controllable number of structural
      defects and demonstrate the number of structural defects can fundamentally
      determine their catalytic activity in selective oxidation of benzyl alcohol by
      O2, with the catalytic activity increasing with the number of structural defects.
      X-ray photoelectron spectroscopy (XPS) and cyclic voltammograms (CVs) studies
      demonstrate that the structural defects can significantly alter the chemical
      state of the Rh WNWs to modulate their catalytic activity. Lastly, our systematic
      studies further demonstrate that the concept of defect engineering in WNWs for
      improved catalytic performance is general and can be readily extended to other
      similar systems, including palladium and iridium WNWs. 

PMID- 24873776
TI  - Transient volume of evaporating sessile droplets: 2/3, 1/1, or another power law?
AB  - The transient shape and volume of evaporating sessile droplets are critical to
      our understanding and prediction of deposits left over on the solid surface after
      droplet evaporation. The 2/3 power law of scaling, (V/Vo)(beta) = 1 - t/tf with
      beta = 2/3, has been widely used. The 1/1 power law of scaling with beta = 1 was
      also obtained for vanishingly small contact angles. Here we show that beta
      significantly deviates from 2/3 and 1 when the droplet base is pinned: beta
      depends on both initial and transient contact angles. The 1/1 power law presents
      the upper limit of beta = 1, while beta = 2/3 is the lower limit if contact
      angles are smaller than 148 degrees . Unexpectedly, beta can be smaller than 2/3
      if contact angles are larger than 148 degrees . We also present a semianalytical
      approximation for beta as a function of the initial contact angle. 

PMID- 24873777
TI  - Biomimetic fabrication of a three-level hierarchical calcium
      phosphate/collagen/hydroxyapatite scaffold for bone tissue engineering.
AB  - A three-level hierarchical calcium phosphate/collagen/hydroxyapatite
      (CaP/Col/HAp) scaffold for bone tissue engineering was developed using biomimetic
      synthesis. Porous CaP ceramics were first prepared as substrate materials to
      mimic the porous bone structure. A second-level Col network was then composited
      into porous CaP ceramics by vacuum infusion. Finally, a third-level HAp layer was
      achieved by biomimetic mineralization. The three-level hierarchical biomimetic
      scaffold was characterized using scanning electron microscopy, energy-dispersive
      x-ray spectra, x-ray diffraction and Fourier transform infrared spectroscopy, and
      the mechanical properties of the scaffold were evaluated using dynamic mechanical
      analysis. The results show that this scaffold exhibits a similar structure and
      composition to natural bone tissues. Furthermore, this three-level hierarchical
      biomimetic scaffold showed enhanced mechanical strength compared with pure porous
      CaP scaffolds. The biocompatibility and osteoinductivity of the biomimetic
      scaffolds were evaluated using in vitro and in vivo tests. Cell culture results
      indicated the good biocompatibility of this biomimetic scaffold. Faster and
      increased bone formation was observed in these scaffolds following a six-month
      implantation in the dorsal muscles of rabbits, indicating that this biomimetic
      scaffold exhibits better osteoinductivity than common CaP scaffolds. 

PMID- 24873778
TI  - Transplant professionals' proposals for the implementation of an altruistic
      unbalanced paired kidney exchange program.
AB  - BACKGROUND: Kidney recipients in the O blood group are at a disadvantage in
      kidney exchange programs (KEPs) because they can only receive an organ from O
      blood group donors. A way to remedy this unfair situation is through altruistic
      unbalanced paired kidney exchange (AUPKE) where a compatible pair (CP) consisting
      of an O donor and a non-O recipient is invited to participate in a KEP. There is
      no established AUPKE program in Canada. The aim of this study was to gather
      transplant professionals' views on the conditions necessary for the
      implementation of an AUPKE program. METHODS: Nineteen Canadian transplant
      professionals took part in semistructured interviews. The content of these
      interviews was analyzed using a qualitative data analysis method. RESULTS:
      Respondents' recommendations focused on the following: (i) the logistics of AUPKE
      (e.g., not delaying the transplantation for the CP, retrieving organs locally,
      providing a good quality organ to the CP, and maintaining anonymity); (ii) the
      transplantation teams (e.g., establishing a consensus among members and ensuring
      sufficient resources); (iii) information provided to CPs; and (iv) research
      (e.g., looking into all transplant options for O recipients, studying all
      potential impacts of KEPs and AUPKE). CONCLUSION: The respondents in our study
      made the following recommendations for the implementation of an AUPKE program:
      (i) CPs should not be disadvantaged, (ii) measures should be taken to ensure that
      all transplant team members agree to participate and that there are sufficient
      resources for implementation, (iii) comprehensive information should be provided
      to the CP, and (iv) further research is needed on AUPKE.

PMID- 24873779
TI  - Risk stratification for in-hospital mortality after heart transplantation using
      the modification of diet in renal disease and the chronic kidney disease
      epidemiology collaboration equations for estimated glomerular filtration rate.
AB  - BACKGROUND: A new equation for estimating glomerular filtration rate (GFR)-the
      Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation-is better at
      predicting outcomes in the general population than the Modification of Diet in
      Renal Disease (MDRD) equation. We compared risk stratification of heart
      transplant (HT) recipients for early post-HT mortality using estimated GFR from
      the MDRD and the CKD-EPI equations. METHODS: We identified all patients 18 years
      or older who underwent their first HT in the United States between January 2007
      and October 2010 (n=6,564). We compared risk stratification for posttransplant in
      hospital mortality by GFR estimated by the CKD-EPI equation versus that estimated
      by the MDRD equation. RESULTS: Posttransplant in-hospital mortality was 4.6%.
      Lower GFR (mL/min/1.73 m2, MDRD) was associated with higher in-hospital mortality
      in adjusted analysis (GFR, 60-89; odds ratio [OR], 1.5; 95% confidence interval
      [CI], 1.0-2.3; GFR, 30-59; OR, 2.2; 95% CI, 1.4-3.3; GFR<30; OR, 3.3; 95% CI, 1.8
      6.1; vs. GFR >= 90). Glomerular filtration rate estimated using the CKD-EPI
      equation reclassified 10%, 15%, and 18% of patients, respectively, in GFR
      categories lower than 30, 30-59, and 60-89 to the next higher GFR category. Using
      the CKD-EPI equation was not associated with a significant net reclassification
      improvement for mortality risk in the overall cohort or in GFR subgroups. The
      risk models of in-hospital mortality developed using the two GFR equations
      performed similarly for discrimination and calibration. CONCLUSION: Estimated GFR
      using the CKD-EPI equation is comparable to estimated GFR using the MDRD equation
      in risk stratification of HT recipients for early posttransplant mortality.

PMID- 24873780
TI  - Pretransplant immunologic risk assessment of kidney transplant recipients with
      donor-specific anti-human leukocyte antigen antibodies.
AB  - BACKGROUND: Patients with pretransplantation strong donor-specific anti-human
      leukocyte antigen (HLA) antibodies (DSA) are at higher risk for rejection. We
      aimed to study the safety of kidney transplantation in patients with lower
      strength DSAs in a prospective cohort study. METHODS: Three hundred and seventy
      three consecutive adult kidney transplant recipients with (DSA+; n=66) and
      without (DSA-; n=307) DSA were evaluated. Anti-HLA antibodies with mean
      fluorescence intensity values over 5,000 for HLA-A, HLA-B, and HLA-DR and more
      than 10,000 for HLA-DQ were reported as unacceptable antigens. Patients received
      transplant if flow cytometry T-cell and B-cell cross-match channel shift values
      were less than 150 and 250, respectively, with antithymocyte globulin and
      intravenous immunoglobulin induction treatment. RESULTS: Patients had a mean
      number of 1.6 +/- 0.8 DSAs with a mean fluorescence intensity value of 2,815 +/-
      2,550. Twenty-seven percent were flow cytometry cross-match positive with T-cell
      and B-cell channel shift values of 129 +/- 49 and 159 +/- 52, respectively.
      During a median follow-up of 24 months (range, 6-50), there were no statistically
      significant differences in patient (99% vs. 95%) and graft survival (88% vs. 90%)
      rates between DSA+ and DSA- groups, respectively. Cumulative acute rejection
      rates of 11% in the DSA+ group and 12% in the DSA- group were similar. Two DSA+
      (3%) and five DSA- (2%) patients developed chronic antibody-mediated rejection
      (3%). The mean serum creatinine levels were identical between the two groups (1.4
      +/- 0.6 mg/dL). CONCLUSION: Similar patient and graft survival, and acute
      rejection rates can be achieved in DSA+ patients compared to DSA- patients with
      pretransplantation immunologic risk assessment.

PMID- 24873781
TI  - Anti-Angiotensin type 1 receptor antibodies in chronic graft-versus-host disease.
AB  - BACKGROUND: Activating anti-angiotensin type 1 receptor antibodies (AT1R-AA) have
      been described in patients with systemic scleroderma, an auto-immune disorder
      with clinical fibrotic features. Chronic graft-versus-host disease (cGvHD) after
      hematopoietic stem cell transplantation may have clinical fibrotic features,
      whose pathogenesis may be similar with systemic sclerosis. OBJECTIVE: To evaluate
      the presence of AT1R-AA and their association with clinical and biological
      symptoms in cGvHD patients. MATERIAL AND METHODS: Sera from 87 patients including
      45 extensive cGvHD and 42 hematopoietic stem cell transplantation patients
      without cGvHD were retrospectively analyzed for the presence of AT1R-AA using an
      enzymatic immunoassay. RESULTS: The frequency of AT1R-AA was significantly
      increased (odds ratio [OR]=3.4, P=0.04) in the cGvHD group (24.4%) compared with
      the non-cGvHD group (7.1%). In the cGvHD group the positivity of AT1R-AA was
      significantly associated with: i/ the presence of antinuclear antibodies (OR=5.9,
      P=0.04) ii/ a more severe global and organ-specific cGvHD scoring (P<0.05), iii/
      the presence of active skin or mucosal erosions (OR=19.2, P<0.01). There was no
      difference between the number and the types of organs involved by the cGvHD
      between the AT1R-AA-positive versus AT1R-AA-negative subgroups. CONCLUSION: This
      preliminary study suggests a potential role and prognostic value of AT1R-AA in
      cGvHD.

PMID- 24873782
TI  - (99m)Tc-methylene diphosphonate bone scintigraphy findings in posttransplant
      distal limb syndrome.
AB  - We report a case of posttransplant distal limb syndrome (PTDLS) representing a
      rare complication in kidney transplant recipients characterized by a pain
      syndrome of the distal extremities. A 68-year-old man with a history of kidney
      transplantation presented with symmetrical and incapacitating pain in the feet
      and knees and underwent whole-body Tc-methylene diphosphonate (MDP) scintigraphy
      for further evaluation. Planar scintigraphy demonstrated marked tracer uptake in
      the distal femoral and tibial epiphyses, and magnetic resonance imaging showed
      corresponding osteoedema. Tc-MDP scintigraphy is a valuable tool for evaluation
      of the etiology of musculoskeletal pain and may demonstrate typical findings in
      case of PTDLS. 

PMID- 24873783
TI  - Diffuse renal (18)F-FDG uptake of a patient with fever of unknown origin revealed
      sarcoidosis.
AB  - We report about the usefulness of F-FDG PET for the detection and therapy
      response evaluation of renal sarcoidosis. A 55-year-old woman presented with a
      condition diagnosed with pulmonary and ocular sarcoidosis 2 years before having
      anemia and acute deterioration of renal function. FDG PET revealed diffuse
      increased FDG uptake in both kidneys and the spleen. Histopathologic examination
      of a renal biopsy sample revealed granulomatous interstitial nephritis with
      sarcoidosis. After methylprednisolone treatment, the abnormal FDG uptake resolved
      completely with improvement of symptoms. FDG PET is a useful tool to detect
      active sarcoidosis regions and to monitor treatment efficacy. 

PMID- 24873784
TI  - Visualization of orbital involvement of Erdheim-Chester disease on PET/CT.
AB  - We report a 58-year-old man who presented with swelling and redness in his left
      eye, headache, and blurred vision. A contrast-enhanced CT of the orbits revealed
      bilateral orbital masses. Whole-body PET/CT showed bilateral retrobulbar
      hypermetabolic soft tissue lesions, multiple areas of soft tissue involvement,
      and osseous lesions in bilateral lower extremities. An open surgical biopsy of
      the left orbital mass revealed xanthomatous non-Langerhans histiocytic infiltrate
      with Touton giant cells, positive for CD68 but negative for CD1a, establishing a
      diagnosis of Erdheim-Chester disease. 

PMID- 24873785
TI  - Consistency of myocardial mass computations as a quality control check on rest
      and stress left ventricular ejection fractions computed from (82)Rb PET data.
AB  - PURPOSE: Changes in left ventricular (LV) ejection fraction (EF) seen in gated Rb
      data are of interest because the heart is in a genuinely different physiologic
      state during stress than at rest. A measure that validates internal consistency
      of LV EF data would be highly desirable. Left ventricular mass calculations are
      performed simultaneously with EF determinations, requiring similar operator
      choices, and although LV volumes may change from rest to stress, mass values
      should be constant. Constancy of LV mass calculations could provide a useful
      internal check on the consistency of LV EF computations. PATIENTS AND METHODS: We
      retrospectively reviewed data for 205 patients referred for evaluation of known
      or suspected coronary disease who had rest and regadenoson stress gated Rb PET/CT
      myocardial perfusion imaging. Equilibrium gated myocardial perfusion PET data
      were analyzed to calculate LV volumes, EF, and simultaneously mass values.
      RESULTS: Rest mass ranged from 62 to 284 g (median, 115 g), stress mass from 39
      to 315 g (median, 120 g), and differences were -25 to +25 g (median, 1 g). Rest
      and stress mass values were statistically similar (121 +/- 37 g vs 124 +/- 49 g,
      P = 0.45) and correlated strongly with one another (r = 0.94, P < 0.0001).
      CONCLUSIONS: Left ventricular mass calculations are constant from rest to stress
      over a wide range of ventricular volumes and ejection fractions. Consistency of
      LV mass values can serve as confirmation of the appropriateness of operator
      choices when LV EF calculations are performed.

PMID- 24873786
TI  - Validation of IAEA software package for the analysis of scintigraphic renal
      dynamic studies: parameters of renal transit in children with renal pelvic
      dilatation.
AB  - PURPOSE: The objectives of the study were to use the International Atomic Energy
      Agency (IAEA) software package for the analysis of scintigraphic renal dynamic
      studies to obtain values of curve parameters and excretory parameters in children
      with hydronephrosis and to validate the reliability of these numerical outputs by
      comparing with values established by consensus reports. PATIENTS AND METHODS:
      Fifty children with hydronephrosis (median age, 16 months; 30 boys, 20 girls; 99
      kidneys) underwent Tc-MAG3 diuresis renography. Studies were analyzed by 2
      observers, and according to the assessment of images, renograms, and differential
      function, kidneys were classified as normal (42, kidneys contralateral to
      hydronephrotic kidney), hypotonic unobstructed (49), and obstructed (8). The IAEA
      software was applied to each renogram. The parameters analyzed were as follows:
      normalized residual activity at 20 minutes (NORA 20) and on postmicturition (PM)
      acquisition, output efficiency at 20 minute (OE 20), PM to maximum renal count
      ratio (PM/max), and mean transit time (MTT). RESULTS: Mean values for normal,
      hypotonic unobstructed, and obstructed kidneys were as follows: NORA 20: 0.25,
      0.57, and 2.16; OE 20 (%): 94.5, 87, and 57; normalized residual activity on PM
      acquisition: 0.02, 0.03, and 0.27; PM/max: 0.01, 0.02, and 0.13; and MTT
      (minutes): 1.9, 3.5, and 8.9, respectively. Difference between
      obstruction/dilatation and normal/dilatation was significant (P < 0.0001), as
      well as the correlation between NORA 20/OE 20 (R = -0.982). Cutoff values to
      predict obstruction were as follows: NORA 20, 1.6; OE 20, 73%; NORA PM, 0.11;
      PM/max, 0.06; and MTT, 8.23 minutes. CONCLUSIONS: The IAEA software package gives
      reliable values of numerical parameters of renal excretion. The use of the
      software improves diagnostic accuracy of diuresis renography in children.

PMID- 24873787
TI  - Comparison of (68)Ga DOTATATE to 18F-FDG uptake is useful in the differentiation
      of residual or recurrent pituitary adenoma from the remaining pituitary tissue
      after transsphenoidal adenomectomy.
AB  - AIM: The evaluation of the remaining pituitary tissue and recurrent or residual
      tumor after the pituitary adenoma resection is difficult. However, it is
      essential to assess the size of the recurrent tumor and remaining pituitary
      reserve before resurgery. This study aimed to distinguish the remaining pituitary
      tissue from pituitary adenoma with Ga 1,4,7,10-tetraazacyclododecane-N,N',N",N"'
      tetraacetic acid-D-Phe,Tyr3-octreotate (DOTATATE) and F-FDG PET imaging in
      patients status post transsphenoidal adenomectomy. METHODS: Thirty-five patients
      with suspected recurrent/residual pituitary tumors were retrospectively
      evaluated. All of these patients underwent DOTATATE and FDG PET/CT within 1 week
      before additional surgery. The DOTATATE and FDG uptake levels were compared. The
      image findings were then compared with pathology results after the additional
      surgery. RESULTS: Residual or recurrent pituitary adenoma were confirmed
      pathologically in all 35 patients. One recurrent pituitary adenoma did not have
      either DOTATATE or FDG uptake. In the remaining 34 adenomas, 33 had higher FDG
      uptake than DOTATATE uptake. In comparison, DOTATATE had significant higher
      uptake than FDG in the remaining pituitary tissues in all cases. CONCLUSIONS:
      Different degree of uptake of Ga DOTATATE and F-FDG PET/CT in the remaining
      pituitary tissue and recurrent/residual pituitary tumor indicated that combined
      analysis of Ga DOTATATE and F-FDG PET/CT might be of clinical value in
      differentiating recurrent/residual pituitary adenoma from the remaining pituitary
      tissue.

PMID- 24873789
TI  - Intense FDG activity in focal hepatic steatosis.
AB  - A 38-year-old woman underwent PET/CT to evaluate possible hepatic malignancy. The
      images revealed intense FDG activity in several hypodense regions in the liver,
      most prominent in the lateral segment of the left lobe. The pathological
      examination showed that the patient had focal hepatic steatosis. 

PMID- 24873790
TI  - Cervical and thoracic actinomycosis on (18)F-FDG PET/CT.
AB  - Actinomycosis is a rare chronic granulomatous disease that runs an indolent
      course, predominantly seen in Asian countries. The present case highlights the
      findings of F-FDG PET/CT in cervicothoracic actinomycosis imitating lymphoma. 

PMID- 24873788
TI  - FDG PET for diagnosing infection in hip and knee prostheses: prospective study in
      221 prostheses and subgroup comparison with combined (111)In-labeled
      leukocyte/(99m)Tc-sulfur colloid bone marrow imaging in 88 prostheses.
AB  - PURPOSE: This study aims to assess and compare the value of FDG PET with combined
      In-labeled leukocyte/Tc-sulfur colloid bone marrow (WBC/BM) imaging for
      diagnosing infection in hip and knee prostheses. METHODS: In this prospective
      study, patients with painful hip or knee arthroplasty, who were scheduled to
      undergo clinical and diagnostic evaluation for prosthesis revision, were
      included. They have been studied by using FDG PET and WBC/BM scan. This study was
      institutional review board approved and Health Insurance Portability and
      Accountability Act compliant. All patients provided written informed consent.
      RESULTS: A total of 134 hip and 87 knee prostheses, suspected of being either
      infected or noninfectious loosening, were evaluated. All 221 prostheses underwent
      FDG PET, whereas both WBC/BM imaging and FDG PET were performed in 88 prostheses.
      The initial analysis of data from the WBC/BM images demonstrated somewhat
      suboptimal results compared with those of FDG PET scans on 88 patients. In
      addition, some patients were not willing to undergo both procedures and therefore
      participate in this study. Therefore, a decision was made to eliminate WBC/BM
      imaging from the procedures for the remainder of this research study. This
      decision was reached partly because of the significant radiation dose delivered
      from labeled WBC and safety issues related to preparing these labeled cells.
      Final diagnosis was based on microbiological examinations of the surgical
      specimens in 125 prostheses and joint aspirations combined with the clinical
      follow-up of 6 months or more in 86 prostheses. The sensitivity, specificity,
      positive predictive value, and negative predictive value of FDG PET in hip
      prostheses were 81.8%, 93.1%, 79.4%, and 94.0%, respectively, and in knee
      prostheses were 94.7%, 88.2%, 69.2%, and 98.4%, respectively. The sensitivity,
      specificity, positive predictive value, and negative predictive value of WBC/BM
      imaging in hip prostheses were 38.5%, 95.7%, 71.4%, and 84.6%, respectively, and
      in knee prostheses were 33.3%, 88.5%, 25.0%, and 92.0%, respectively. In those
      cases that underwent both FDG PET and WBC/BM imaging, there was a trend (P =
      0.0625) toward a higher sensitivity for FDG PET in hip prostheses, whereas other
      comparisons did not show any significant differences between the 2 imaging
      modalities. CONCLUSIONS: Based on this study, the diagnostic performance of FDG
      PET scan in detecting infection in painful hip and knee prostheses is optimal for
      routine clinical application. Considering the complexity and costs of WBC/BM
      imaging and related safety issues associated with this preparation, FDG PET seems
      to be an appropriate alternative for assessing these patients.

PMID- 24873791
TI  - Subclinical seizures as a pitfall in 18F-FDG PET imaging of temporal lobe
      epilepsy.
AB  - A 61-year-old man with history of heroin abuse, hepatitis B, hepatitis C, and
      hypertension was evaluated for seizures. MRI findings were concerning for
      temporal epilepsy. A brain 18F-FDG PET study showed a hypermetabolic focus in the
      left temporal lobe, although the patient was asymptomatic during the scan. Later
      review of electroencephalography recordings revealed a subclinical seizure during
      imaging. A whole-body 18F-FDG PET scan performed 4 days later for cancer
      screening purposes, during which the electroencephalography tracings were normal,
      showed no abnormal metabolic activity in the brain.

PMID- 24873792
TI  - (99m)Tc HYNIC-TOC imaging and 177Lu DOTA-octreotate treatment in non-iodine
      concentrating dedifferentiated thyroid carcinoma metastases: an unusual
      alternative diagnosis.
AB  - The value of Tc HYNIC-TOC scintigraphy clarifying skeletal and hepatic
      predominant metastatic disease in a 55-year-old woman (diagnosed earlier to have
      papillary carcinoma thyroid and had undergone total thyroidectomy and radioiodine
      ablation) is illustrated. The whole-body radioiodine scan and battery of serum
      tumor markers were normal. Multiple metastatic foci in the liver and skeleton
      were Tc HYNIC-TOC avid. Serum chromogranin A level was substantially elevated
      (1771.60 ng/mL). This represents an unusual alternative diagnosis signified by a
      highly positive scan in the setting of apparent non-iodine-concentrating
      metastatic disease in a patient of differentiated thyroid carcinoma. 

PMID- 24873793
TI  - Inflammatory myofibroblastic tumor of the lung indistinguishable from
      adenocarcinoma on imaging studies.
AB  - We present the case of a right lung nodule discovered on routine chest x-ray in
      an asymptomatic 62-year-old man. CT revealed a spiculated nodule in segment 1 of
      the right upper lobe, 2.2 cm in diameter and without calcification. The nodule
      showed high focal FDG uptake (SUVmax, 17.8) on PET. Right upper lobectomy was
      performed under the diagnosis of adenocarcinoma; however, the histopathologic
      findings were of inflammatory myofibroblastic tumor. 

PMID- 24873795
TI  - Diffuse liver uptake on (99m)Tc-MDP bone scan secondary to severe hepatic
      failure.
AB  - Hepatic uptake on an MDP bone scan is a non-specific finding. When present, the
      etiology needs to be determined. The differential diagnosis depends on the
      pattern of uptake. Metastatic breast and colon cancer are frequent causes of
      focal faint uptake. Diffuse uptake is rare, but can be seen with hepatitis,
      amyloid, and IV gadolinium administration. In addition, aluminum breakthrough
      from the molybdenum generator can cause colloid formation and subsequent diffuse
      hepatic uptake. We present a case of diffuse uptake in a patient with acute
      hepatic failure. The etiology of the failure was extensive thrombosis of the
      inferior vena cava (IVC). 

PMID- 24873794
TI  - Liver standardized uptake value corrected for lean body mass at FDG PET/CT:
      effect of FDG uptake time.
AB  - OBJECTIVE: The objective of this study is to establish the magnitude change and
      interreader reliability of the liver standardized uptake value corrected for lean
      body mass (SULmean) in dual-time-point imaging at 1 and 2 hours and 1 and 4
      hours. PATIENTS AND METHODS: Early and delayed FDG PET/CT scans were included for
      28 patients (13 men and 15 women) who had normal liver by CT or ultrasound. The
      average uptake time between the early and delayed scans were 55 minutes (range,
      44-69 minutes) for pancreatic adenocarcinoma patients (n = 19) and 184 minutes
      (range, 140-197 minutes) for neurofibromatosis patients (n = 9). A 30-mm-diameter
      spherical volume of interest was placed within the right lobe of the liver above,
      below, and at the level of the main portal vein by 2 independent readers.
      Correlation coefficients, analysis of variance, intraclass correlation
      coefficient, and Bland-Altman analysis were performed. RESULTS: The mean liver
      SULmean was between 1.39 and 1.42 and between 1.28 and 1.3 in early and delayed
      images, respectively (P = 0.001). There is time-dependent reduction in the mean
      liver SULmean at 2-hour (7%-8%) and 4-hour uptake time (15%-21%) compared with 1
      hour uptake time. The correlation coefficient between delayed uptake time and
      liver SULmean reduction is 0.39 to 0.41 at the upper aspect of the liver. The
      intraclass correlation coefficient for 2 readers varied between 0.997 and 0.998
      and between 0.995 and 0.999 in early and delayed images, respectively (P =
      0.001). CONCLUSIONS: There is time-dependent reduction of mean liver SULmean,
      about 7% to 8% within the clinically relevant FDG uptake time, in the same
      patient with excellent interreader agreement in early and delayed images within
      the right lobe of the liver. Therefore, liver SULmean could represent a useful
      reference parameter in quantitative analysis of dual-phase FDG PET/CT in
      malignancy or atypical infection/inflammatory disease. Furthermore, it may be
      suitable as a normalization factor in currently available formulae quantifying
      therapy response on PET imaging.

PMID- 24873796
TI  - Intraperitoneal urine leak after prostatectomy confirmed by 99mTc-MAG3 renogram.
AB  - A 67-year-old patient presented with abdominal pain and distension 2 days after
      robotic radical prostatectomy for prostate carcinoma. He became anuric, and his
      serum creatinine level doubled, making IV contrast contraindicated. Abdominal CT
      without contrast demonstrated hypodense fluid in the peritoneum. Tc-MAG3 renogram
      detected extravasation of radiotracer from the bladder. Follow-up retrograde
      cystogram revealed a posterior anastomotic leak. The patient underwent uneventful
      surgical repair and made a full recovery. This case demonstrated that Tc-MAG3 can
      prove leak from the urinary tract, particularly helpful in the setting of poor
      renal function and contraindication to IV contrast. 

PMID- 24873797
TI  - Decreased metabolic uptake in tuberculous pericarditis indicating response to
      antituberculosis therapy on FDG PET/CT.
AB  - Early diagnosis and adequate treatment of tuberculosis are important for disease
      control and prevention of complication. However, diagnosing disease is frequently
      delayed because of difficulties of bacilli isolation or reproduction in cultures,
      and also, the decision of the efficiency of treatment sometimes can be
      impossible. FDG PET has become a promising imaging modality in the field of
      infection and inflammation, especially for the extension and severity of disease.
      Here, we describe an unusual case of tuberculous pericarditis that shows marked
      increased FDG uptake on initial scan, with decreasing metabolic activity on
      follow-up scan indicating response to antituberculosis therapy. 

PMID- 24873798
TI  - Improvement in diagnosis of metastatic pituitary carcinoma by 68Ga DOTATATE
      PET/CT.
AB  - Pituitary carcinoma is a rare disease with a challenge in both diagnosis and
      treatment. A 50-year-old female patient who underwent transsphenoidal resection
      of a pituitary tumor experienced progressive headache. For the evaluation, Ga
      DOTATATE PET/CT was used and compared with F-FDG PET/CT and enhanced MRI.
      Multiple lesions were detected by Ga DOTATATE PET/CT at the cerebral cortex,
      cerebellum, and cerebellopontine angle with a higher contrast than F-FDG PET/CT
      and enhanced MRI. With a biopsy, the patient was diagnosed as metastatic
      pituitary carcinoma. Moreover, it thus presents potential therapeutic
      implications on molecular-targeted therapy using somatostatin analogs and peptide
      receptor radionuclide therapy targeting the somatostatin receptors. 

PMID- 24873800
TI  - Benign fibrous histiocytoma of a rib.
AB  - Rib benign fibrous histiocytoma (BFH) is an uncommon entity. We came across a 20
      year-old Chinese man who complained of right chest pain for 2 weeks. All
      laboratory examination results were normal. CT of the thorax revealed an
      expansible bone lesion in the right sixth anterior rib. Whole-body bone scan
      demonstrated intense tracer uptake in the lesion without other abnormalities. The
      patient underwent en bloc resection. Pathological diagnosis confirmed the
      diagnosis of rib BFH. This report underlines that when whole-body bone scan
      displays solitary uptake of a rib lesion, rib BFH should be considered in the
      differential diagnosis. 

PMID- 24873799
TI  - PET/CT findings in a case with FDG-avid disseminated lacrimal gland MALToma with
      sequential development of large B-cell lymphoma and gastric MALToma.
AB  - Primary orbital lymphomas are rare; the major histopathologic type is extranodal
      marginal-zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) or
      MALToma. We present a case of a 79-year-old female patient with FDG-avid lacrimal
      gland MALToma with nodal and pulmonary involvement (stage IVE). Nasopharynx and
      gastric involvement were detected on restaging F-FDG PET/CT after rituximab
      therapy, and it was found to have a site of transformation to diffuse large B
      cell lymphoma (DLBCL) in the nasopharynx. Gastric MALT lymphoma was also
      confirmed histopathologically, and she then underwent combination chemotherapy
      regimen, resulting in regression after 3 courses. 

PMID- 24873801
TI  - Tips for a physician in getting the right job, part XII: general questions for
      the applicant to ask.
AB  - The type and caliber of the questions asked by a job hunter is one of the ways an
      interviewer will evaluate the candidate. Questions that show poor preparation
      should not be asked, such as failure to read what the employer sent to the job
      seeker or not doing elementary research on the practice, the organization, or the
      community. Asking about insignificant details also is not helpful. Not having any
      good questions to ask is a negative in an interview. This article discusses many
      possible important questions for the applicant to ask during an interview. 

PMID- 24873802
TI  - FDG PET/CT depicts cutaneous plasmocytoma.
AB  - A 63-year-old man with a 1-year course of IgA-lambda multiple myeloma (MM) and a
      history of autologous stem cell transplantation presented with multiple
      nontender, nodular violaceous skin lesions that were located predominantly on his
      trunk. Diagnostic workup using F-FDG PET/CT revealed disseminated disease
      including highly hypermetabolic (sub)cutaneous lesions, consistent with active
      manifestations of MM. Histopathology confirmed monoclonal, lambda-restricted
      plasma cell infiltrates with a high proliferation index (Ki-67) of about 80%.
      Cutaneous manifestation of MM is an uncommon observation in clinical practice
      portending poor prognosis. 

PMID- 24873803
TI  - Myocardial metastases from renal cell carcinoma mimicking ischemia on myocardial
      perfusion scintigraphy.
AB  - A 60-year-old man with history of metastatic renal cell carcinoma and atypical
      chest pain was referred for dipyridamole Tc-tetrofosmin perfusion scintigraphy
      (MPS). Two years earlier, the patient was noted to have myocardial metastases on
      cardiac MRI. On the MPS, perfusion defects were present at stress in multiple
      vascular territories; resting myocardial uptake was homogeneous. These findings
      suggested multivessel atherosclerotic heart disease. In fact, retrospective rigid
      fusion with prior chest CT and cardiac MRI demonstrated that the reversible
      perfusion defects corresponded to metastatic deposits in the myocardium. This
      unusual case illustrates how myocardial metastases can mimic ischemia on MPS. 

PMID- 24873806
TI  - [The PRAMI study].

PMID- 24873804
TI  - Generation of organized germ layers from a single mouse embryonic stem cell.
AB  - Mammalian inner cell mass cells undergo lineage-specific differentiation into
      germ layers of endoderm, mesoderm and ectoderm during gastrulation. It has been a
      long-standing challenge in developmental biology to replicate these organized
      germ layer patterns in culture. Here we present a method of generating organized
      germ layers from a single mouse embryonic stem cell cultured in a soft fibrin
      matrix. Spatial organization of germ layers is regulated by cortical tension of
      the colony, matrix dimensionality and softness, and cell-cell adhesion.
      Remarkably, anchorage of the embryoid colony from the 3D matrix to collagen-1
      coated 2D substrates of ~1 kPa results in self-organization of all three germ
      layers: ectoderm on the outside layer, mesoderm in the middle and endoderm at the
      centre of the colony, reminiscent of generalized gastrulating chordate embryos.
      These results suggest that mechanical forces via cell-matrix and cell-cell
      interactions are crucial in spatial organization of germ layers during mammalian
      gastrulation. This new in vitro method could be used to gain insights on the
      mechanisms responsible for the regulation of germ layer formation. 

PMID- 24873807
TI  - [The TASTE study].

PMID- 24873805
TI  - Interactive contribution of serine/threonine kinase 39 gene multiple
      polymorphisms to hypertension among northeastern Han Chinese.
AB  - Serine/threonine kinase 39 (STK39) gene has been reported to be a hypertension
      susceptibility gene by a recent genome-wide association study in Western
      populations. To validate this finding in Chinese, we focused on five well
      characterized common polymorphisms in STK39 gene to examine their potential
      association with hypertension in a large northeastern Han population. This is a
      hospital-based case-control study involving 1009 hypertensive patients and 756
      normotensive controls. Data were analyzed by the Haplo.Stats and multifactor
      dimensionality reduction (MDR) softwares. The genotype and allele distributions
      of rs6749447, rs3754777 and rs6433027 differed significantly between patients and
      controls (P < 0.001) even after the Bonferroni correction. The majority of
      derived haplotypes also showed remarkable differences between the two groups (P
      <= 0.001). As indicated by MDR analysis, a three-locus model including rs6749447,
      rs35929607 and rs3754777 was selected as the overall best with a larger testing
      accuracy of 0.7309 and a maximum cross-validation consistency of 10 (P < 0.001).
      The utility of this model was reinforced by a Logistic regression analysis. Taken
      together, our findings suggest the potential interactive role of STK39 gene
      multiple polymorphisms in the development of hypertension among northeastern Han
      Chinese. 

PMID- 24873808
TI  - [Stable angina: what the European guidelines say or do not say].

PMID- 24873809
TI  - [The new 2013 European guidelines on pacing and cardiac resynchronization
      therapy: between confirmation and novelty].

PMID- 24873810
TI  - [Multination clinical trials: what is the relevance and what are the lessons from
      across-country differences?].
AB  - In the cardiovascular area, the rate of occurrence of relevant clinical events
      decreased over the last decades due to the large adoption of evidence-based
      treatments. This implies that large numbers of patients are needed to provide
      reliable answers to research open questions. Therefore, the conduction of
      multinational large-scale studies became necessary. In this setting, it is not
      infrequent to find relevant differences in the trial results across countries.
      The interpretation of these differences should be extremely cautious to avoid the
      well known mistakes related to subgroup analyses. To believe in differences, it
      is necessary to adopt appropriate methodologies in the analysis of data but, even
      more important, to find a biological plausibility that can explain the observed
      difference. A further confirmation from other studies can also help in the
      interpretation. In the literature there are some examples of such differences
      that, in some cases, produced erroneous interpretations of the results of a
      trial, and also induced regulatory authorities to take decisions based on these
      differences. 

PMID- 24873811
TI  - [Geographical differences in clinical characteristics and management of stable
      outpatients with coronary artery disease: comparison between the Italian and
      international population included in the Worldwide CLARIFY registry].
AB  - BACKGROUND: Limited data are available regarding specific differences among
      countries in demographic and clinical characteristics and treatment of patients
      with stable coronary artery disease. METHODS: CLARIFY is an international,
      prospective and longitudinal registry including more than 33 000 patients with
      stable coronary artery disease enrolled in 45 countries worldwide. Data were used
      to compare the characteristics of patients enrolled in Italy with those enrolled
      in Europe and in the rest of the world. RESULTS: Baseline data were available for
      33 283 patients, 2112 of whom from Italy and 12 614 from the remaining western
      European countries. Italian patients were found to be older, more frequently
      smoker, hypertensive and with sedentary habits. In addition, they presented more
      frequently a history of myocardial infarction, carotid arterial disease and
      chronic obstructive pulmonary disease. In addition, when compared with patients
      of both European and international cohorts, more Italian patients had undergone
      coronary angiography and angioplasty. As far as treatment was concerned, a
      greater number of Italian patients were taking ivabradine, angiotensin-converting
      enzyme inhibitors and/or angiotensin receptor blockers, nitrates,
      thienopyridines, while those taking beta-blockers, calcium antagonists and other
      antianginal medications were fewer. CONCLUSIONS: Among ambulatory patients with
      stable coronary artery disease, there are important geographic differences in
      terms of risk factors, clinical characteristics, surgical and pharmacological
      treatment.

PMID- 24873812
TI  - [Clinical and economical comparison between in-house (Make) and outsourcing (Buy)
      management of the cardiac catheterization laboratory from two high-volume
      diagnostic and interventional centers: immediate and 6-month results].
AB  - BACKGROUND: Percutaneous coronary interventions (PCI) are widespread procedures
      in the Italian Healthcare System, but concerns are raised about their economic
      sustainability. In the last decade, public hospitals have outsourced the PCI
      services (building and maintaining the technological instruments and the
      personnel) "buying" them from private companies (Buy) rather than building and
      maintaining them through public expenditure (Make). The aim of this study was to
      compare the economic and clinical impact of these two management solutions (Buy
      and Make) in two community hospitals located in the Turin metropolitan area
      (Italy). METHODS: We conducted: 1) a quantitative assessment in order to compare
      differences in the economic impact between Buy and Make for providing PCI; 2) a
      qualitative assessment comparing the clinical characteristics of two inpatient
      populations undergoing PCI and then analyzing the efficacy of the procedure in
      hospital and at 6-month follow-up. RESULTS: Between January and June 2010, a
      total of 332 patients underwent PCI at the "degli Infermi" Hospital in Rivoli and
      340 at the "Maria Vittoria" Hospital in Turin (Italy). There were no significant
      differences between the two populations neither about the clinical
      characteristics nor in procedural efficacy (either immediate or at follow-up).
      For 600 units of diagnostic-therapeutic pathway, the net present value at a
      discount rate of 3.5% of the Make project is higher than that of the Buy by
      ?278.402,25, and is therefore the less convenient of the two solutions. The Buy
      solution is still the more convenient of the two at volumes <700 units.
      CONCLUSIONS: Our findings show that the Buy solution, if tailored to the specific
      local needs, provides access to sophisticated technology without making worse
      quality of services and may save capital expenditure below 700 PCI/years.

PMID- 24873813
TI  - [Safe dose rTPA for massive pulmonary embolism associated with high bleeding
      risk: a case report and review of the literature].
AB  - Systemic thrombolysis is a well known treatment for massive pulmonary embolism
      (PE) but it remains often underutilized in clinical practice because of the risk
      of major bleeding, especially intracranial hemorrhage. Recently, the use of safe
      dose recombinant tissue-type plasminogen activator (rTPA) has been proposed for
      the treatment of moderate PE demonstrating to be safe and more effective than
      standard anticoagulation. We report the case of an 83-year-old male patient
      affected by massive PE associated with high bleeding risk, and treated with half
      dose of rTPA that resulted in rapid clinical improvement. This clinical
      experience led us to focus on the role of reduced doses of rTPA to decrease
      bleeding risk in patients with PE. We conclude that the new concept of "safe-dose
      thrombolysis" with rTPA may be considered a reasonable and interesting option in
      high-bleeding risk patients with massive PE. 

PMID- 24873814
TI  - [Choosing wisely: the Top 5 list of the Italian Association of Hospital
      Cardiologists (ANMCO)].
AB  - In recent years, a progressive increase in the number of medical diagnostic and
      interventional procedures has been observed, namely in cardiology. A significant
      proportion of them appear inappropriate, i.e. potentially redundant, harmful,
      costly, and useless. Recently, the document Medical Professionalism in the New
      Millennium: A Physician Charter, the American Board of Internal Medicine (ABIM)
      Foundation Putting the Charter into Practice program, JAMA's Less Is More and
      BMJ's Too Much Medicine series, and the American College of Physicians' High
      Value, Cost-Conscious Care initiatives, have all begun to provide direction for
      physicians to address pervasive overuse in health care. In 2010, the Brody's
      proposal to scientific societies to indicate the five medical procedures at high
      inappropriateness risk inspired the widely publicized ABIM Foundation's Choosing
      Wisely campaign. As part of Choosing Wisely, each participating specialty society
      has created lists of Things Physicians and Patients Should Question that provide
      specific, evidence-based recommendations physicians and patients should discuss
      to help make wise decisions about the most appropriate individual care. In Italy,
      Slow Medicine launched the analogue campaign Fare di piu non significa fare
      meglio. The Italian Association of Hospital Cardiologists (ANMCO) endorsed the
      initiative by recognizing the need to optimize available resources, reduce costs
      and avoid unnecessary cardiovascular assessments, thereby enhancing the more
      efficient care delivery models. An ad hoc ANMCO Working Group prepared a list of
      five cardiac procedures that seem inappropriate for routine use in our country
      and, after an internal revision procedure, these are presented here. 

PMID- 24873815
TI  - [Appropriateness of diagnostic tests in cardiovascular prevention: what can we
      skip?].
AB  - In recent years, a huge increase in the use of cardiac procedures, both invasive
      and non-invasive, was observed. Diagnostic tests, mainly non-invasive tests, are
      often prescribed inappropriately, in most cases replacing the clinical
      evaluation. The rate of inappropriate tests in cardiology is largely variable,
      depending on regional issues and different medical approach. When the test
      entails radiation exposure, the biological risk for both the patient and the
      environment must be taken into account. For this reason, the test that results in
      less biological risk should always be preferred as a first step.Moreover, it has
      not been clearly demonstrated that some diagnostic tests help to improve the
      outcome, that is to prevent cardiovascular events. As many as one sixth of the
      patients who undergo stress imaging are not taking proper medication, and very
      frequently no change in therapy is made after the test, regardless of the
      outcome. Since the appropriateness of diagnostic evaluation requests is
      mandatory, we focused on the diagnostic tests usually performed in primary and
      secondary prevention that carry no contribution to the clinical management of
      patients. This review addresses the need to optimize available resources, reduce
      costs and avoid unnecessary cardiovascular assessments, thereby enhancing the
      more efficient care delivery models. 

PMID- 24873816
TI  - [Takotsubo or peripartum cardiomyopathy? A challenging clinical dilemma].

PMID- 24873817
TI  - [Observation and rehabilitation after pediatric cardiac surgery].

PMID- 24873818
TI  - Traditional Chinese medicine--sea urchin.
AB  - The sea urchin is an ancient, common, seafloor-dwelling marine invertebrate that
      belongs to the phylum Echinodermata. There are multiple species of sea urchin
      with resources that are widely distributed in China, where they were used in
      ancient times as Traditional Chinese Medicine for treating a variety of diseases.
      At present, it is known that the shell, spine and gonad of the sea urchin have
      many medicinal values determined through modern research. In this paper, we
      summarized the major chemical constituents and medicinal value of the sea urchin.

PMID- 24873819
TI  - Current concepts on cardiovascular stent devices.
AB  - Coronary artery stents used for the treatment of patients with coronary artery
      disease develop the practice of interventional cardiology after they were first
      introduced in the mid-1980s. Since then, with dozens of companies involved in the
      development of new and innovative anti-restenotic drugs, polymeric coatings and
      stent platforms has made significant progress in this area. Today, the challenge
      is the conception of the "ideal" coronary stent designed to respond to the
      patient health difficulty. In this context, the literature in the field is quite
      dynamic and successful. The aim of this article is to provide a systematic review
      on the interdisciplinary field literature of the evolution of these medical
      devices by describing the current status, importance and different types of
      stents used in clinical practice. After the presentation of cardiovascular
      problems associated to stenting therapy, the authors describe the bare metal
      stents, the generations of drug eluting stents and the future in progress
      directions regarding: the stents based on biodegradable/bioresorbable polymers,
      polymer-free metal platforms, fully biodegradable scaffolds, as well as drug
      delivery mediated by stent-targeted magnetic nanoparticles. 

PMID- 24873820
TI  - The effects of caffeine on the cholinergic system.
AB  - Caffeine is a secondary metabolite of tea and coffee plants. It is the active
      psychostimulant ingredient of widely consumed beverages, chocolate and some drugs
      as well. The major pathways for caffeine including interaction with adenosine
      receptors have been identified but caffeine has several minor pathways as well
      that remain poorly understood including the cholinergic system. Given the role of
      caffeine in the cholinergic system, some molecular targets have been tracked and
      a mechanism of its action has been proposed in research studies. However, the
      biological effect of caffeine on the cholinergic system is not completely
      understood. The present review focuses on the role of caffeine in the cholinergic
      system. 

PMID- 24873821
TI  - The assessment and characterisation of drug plasma protein binding in the body
      using QSAR.
AB  - Most drugs are carried from the site of absorption to their intended site of
      action (target site) by the bloodstream, either dissolved in the serum or bound
      to plasma proteins. Binding to plasma proteins influences (i.e. limits or
      favours), drug distribution through the body. Usually it is the unbound drug
      concentration that determines its pharmacological and toxicological properties.
      Our ability to design suitable drug candidates depends on our ability to
      understand the molecular characteristics of drug-protein binding and ideally be
      able to predict the extent of binding in vivo. Here we review the different
      approaches that have been used to model and predict the binding of drugs and drug
      like molecules to plasma proteins in the body. 

PMID- 24873822
TI  - Structure and aggregation in the 1,3-dialkyl-imidazolium
      bis(trifluoromethylsulfonyl)imide ionic liquid family: 2. From single to double
      long alkyl side chains.
AB  - A systematic molecular dynamics study using large simulation boxes has been
      performed in order to extend the analysis of the mesoscopic segregation behavior
      observed in ionic liquids of the 1,3-dialkyl-imidazolium
      bis(trifluoromethylsulfonyl)imide homologous series, [C(n)C(mim)][Ntf2] (2 <= n
      <= 10, 2 <= m <= n). The analyses include the discussion of the structure
      factors, S(q), in the low-q range (1.6 <= q/nm(-1) <= 20); the confirmation of
      the periodicity of the polar network of the ionic liquid and its relation to the
      so-called intermediate peaks; and the characterization of the polar network and
      the nonpolar regions that are formed along the series using aggregate analyses by
      means of five different statistical tools. The analyses confirmed that the
      percolation of the nonpolar regions into a continuous domain occurs when the
      total number of carbon atoms in the alkyl chains exceeds six but that this is not
      a sufficient condition for the emergence of a distinct and intense prepeak. The
      existence of such a peak also requires that the longer alkyl chain contains more
      than a critical alkyl length (CAL) of five carbon atoms.

PMID- 24873824
TI  - Tumor-to-tumor metastasis: report of two cases of renal cell carcinoma
      metastasizing to microcystic serous cystadenoma of the pancreas.
AB  - Metastatic cancer to the pancreas accounts for less than 2% of all pancreatic
      malignancies. In contrast to other metastatic tumors, renal cell carcinoma (RCC)
      has a propensity to metastasize as a solitary pancreatic lesion. While
      symptomatic patients may present with obstructive jaundice, abdominal pain, or
      gastrointestinal bleeding, the diagnosis of metastatic pancreatic involvement is
      often made in asymptomatic patients, during follow-up evaluation in the aftermath
      of an initial diagnosis of renal cell carcinoma. Microcystic serous cystadenoma
      of the pancreas is an uncommon pancreatic exocrine neoplasm that morphologically
      resembles conventional (clear cell) RCC, in so far as both tumors are
      characterized by neoplastic cells with clear cytoplasm, relatively uniform nuclei
      and scant associated tumor stroma. Herein, we report 2 immunohistochemically
      confirmed cases of unsuspected metastatic RCC to the pancreas, with the
      metastatic tumor in each case confined to a preexisting microcystic serous
      cystadenoma of the pancreas. 

PMID- 24873823
TI  - Structural insights into higher order assembly and function of the bacterial
      microcompartment protein PduA.
AB  - Bacterial microcompartments are large proteinaceous assemblies that are found in
      the cytoplasm of some bacteria. These structures consist of proteins constituting
      a shell that houses a number of enzymes involved in specific metabolic processes.
      The 1,2-propanediol-utilizing microcompartment is assembled from seven different
      types of shell proteins, one of which is PduA. It is one of the more abundant
      components of the shell and intriguingly can form nanotubule-like structures when
      expressed on its own in the cytoplasm of Escherichia coli. We propose a model
      that accounts for the size and appearance of these PduA structures and underpin
      our model using a combinatorial approach. Making strategic mutations at Lys-26,
      Val-51, and Arg-79, we targeted residues predicted to be important for PduA
      assembly. We present the effect of the amino acid residue substitution on the
      phenotype of the PduA higher order assemblies (transmission electron microscopy)
      and the crystal structure of the K26D mutant with one glycerol molecule bound to
      the central pore. Our results support the view that the hexamer-hexamer
      interactions seen in PduA crystals persist in the cytoplasmic structures and
      reveal the profound influence of the two key amino acids, Lys-26 and Arg-79, on
      tiling, not only in the crystal lattice but also in the bacterial cytoplasm.
      Understanding and controlling PduA assemblies is valuable in order to inform
      manipulation for synthetic biology and biotechnological applications. 

PMID- 24873825
TI  - Ten global "hotspots" for the neglected tropical diseases.

PMID- 24873827
TI  - Neuronal spike initiation modulated by extracellular electric fields.
AB  - Based on a reduced two-compartment model, the dynamical and biophysical mechanism
      underlying the spike initiation of the neuron to extracellular electric fields is
      investigated in this paper. With stability and phase plane analysis, we first
      investigate in detail the dynamical properties of neuronal spike initiation
      induced by geometric parameter and internal coupling conductance. The geometric
      parameter is the ratio between soma area and total membrane area, which describes
      the proportion of area occupied by somatic chamber. It is found that varying it
      could qualitatively alter the bifurcation structures of equilibrium as well as
      neuronal phase portraits, which remain unchanged when varying internal coupling
      conductance. By analyzing the activating properties of somatic membrane currents
      at subthreshold potentials, we explore the relevant biophysical basis of spike
      initiation dynamics induced by these two parameters. It is observed that
      increasing geometric parameter could greatly decrease the intensity of the
      internal current flowing from soma to dendrite, which switches spike initiation
      dynamics from Hopf bifurcation to SNIC bifurcation; increasing internal coupling
      conductance could lead to the increase of this outward internal current, whereas
      the increasing range is so small that it could not qualitatively alter the spike
      initiation dynamics. These results highlight that neuronal geometric parameter is
      a crucial factor in determining the spike initiation dynamics to electric fields.
      The finding is useful to interpret the functional significance of neuronal
      biophysical properties in their encoding dynamics, which could contribute to
      uncovering how neuron encodes electric field signals. 

PMID- 24873828
TI  - New insights into rotavirus entry machinery: stabilization of rotavirus spike
      conformation is independent of trypsin cleavage.
AB  - The infectivity of rotavirus, the main causative agent of childhood diarrhea, is
      dependent on activation of the extracellular viral particles by trypsin-like
      proteases in the host intestinal lumen. This step entails proteolytic cleavage of
      the VP4 spike protein into its mature products, VP8* and VP5*. Previous cryo
      electron microscopy (cryo-EM) analysis of trypsin-activated particles showed well
      resolved spikes, although no density was identified for the spikes in uncleaved
      particles; these data suggested that trypsin activation triggers important
      conformational changes that give rise to the rigid, entry-competent spike. The
      nature of these structural changes is not well understood, due to lack of data
      relative to the uncleaved spike structure. Here we used cryo-EM and cryo-electron
      tomography (cryo-ET) to characterize the structure of the uncleaved virion in two
      model rotavirus strains. Cryo-EM three-dimensional reconstruction of uncleaved
      virions showed spikes with a structure compatible with the atomic model of the
      cleaved spike, and indistinguishable from that of digested particles. Cryo-ET and
      subvolume average, combined with classification methods, resolved the presence of
      non-icosahedral structures, providing a model for the complete structure of the
      uncleaved spike. Despite the similar rigid structure observed for uncleaved and
      cleaved particles, trypsin activation is necessary for successful infection.
      These observations suggest that the spike precursor protein must be
      proteolytically processed, not to achieve a rigid conformation, but to allow the
      conformational changes that drive virus entry. 

PMID- 24873829
TI  - Metabolomics profiling for identification of novel potential markers in early
      prediction of preeclampsia.
AB  - OBJECTIVE: The first aim was to investigate specific signature patterns of
      metabolites that are significantly altered in first-trimester serum of women who
      subsequently developed preeclampsia (PE) compared to healthy pregnancies. The
      second aim of this study was to examine the predictive performance of the
      selected metabolites for both early onset [EO-PE] and late onset PE [LO-PE].
      METHODS: This was a case-control study of maternal serum samples collected
      between 8+0 and 13+6 weeks of gestation from 167 women who subsequently developed
      EO-PE n = 68; LO-PE n = 99 and 500 controls with uncomplicated pregnancies.
      Metabolomics profiling analysis was performed using two methods. One has been
      optimized to target eicosanoids/oxylipins, which are known inflammation markers
      and the other targets compounds containing a primary or secondary biogenic amine
      group. Logistic regression analyses were performed to predict the development of
      PE using metabolites alone and in combination with first trimester mean arterial
      pressure (MAP) measurements. RESULTS: Two metabolites were significantly
      different between EO-PE and controls (taurine and asparagine) and one in case of
      LO-PE (glycylglycine). Taurine appeared the most discriminative biomarker and in
      combination with MAP predicted EO-PE with a detection rate (DR) of 55%, at a
      false-positive rate (FPR) of 10%. CONCLUSION: Our findings suggest a potential
      role of taurine in both PE pathophysiology and first trimester screening for EO
      PE.

PMID- 24873831
TI  - Copper-catalyzed 5-endo-trig cyclization of ketoxime carboxylates: a facile
      synthesis of 2-arylpyrroles.
AB  - A novel and facile copper-catalyzed 5-endo-trig cyclization of ketoxime
      carboxylates for the synthesis of 2-arylpyrroles has been developed. The reaction
      tolerates a range of functional groups and is a practical procedure for rapid
      synthesis of 2-arylpyrroles in high yields under mild conditions. 

PMID- 24873832
TI  - Iterative model reconstruction: improved image quality of low-tube-voltage
      prospective ECG-gated coronary CT angiography images at 256-slice CT.
AB  - OBJECTIVES: To investigate the effects of a new model-based type of iterative
      reconstruction (M-IR) technique, the iterative model reconstruction, on image
      quality of prospectively gated coronary CT angiography (CTA) acquired at low-tube
      voltage. METHODS: Thirty patients (16 men, 14 women; mean age 52.2 +/- 13.2
      years) underwent coronary CTA at 100-kVp on a 256-slice CT. Paired image sets
      were created using 3 types of reconstruction, i.e. filtered back projection
      (FBP), a hybrid type of iterative reconstruction (H-IR), and M-IR. Quantitative
      parameters including CT-attenuation, image noise, and contrast-to-noise ratio
      (CNR) were measured. The visual image quality, i.e. graininess, beam-hardening,
      vessel sharpness, and overall image quality, was scored on a 5-point scale.
      Lastly, coronary artery segments were evaluated using a 4-point scale to
      investigate the assessability of each segment. RESULTS: There was no significant
      difference in coronary arterial CT attenuation among the 3 reconstruction
      methods. The mean image noise of FBP, H-IR, and M-IR images was 29.3 +/- 9.6,
      19.3 +/- 6.9, and 12.9 +/- 3.3 HU, respectively, there were significant
      differences for all comparison combinations among the 3 methods (p<0.01). The CNR
      of M-IR was significantly better than of FBP and H-IR images (13.5 +/- 5.0 [FBP],
      20.9 +/- 8.9 [H-IR] and 39.3 +/- 13.9 [M-IR]; p<0.01). The visual scores were
      significantly higher for M-IR than the other images (p<0.01), and 95.3% of the
      coronary segments imaged with M-IR were of assessable quality compared with 76.7%
      of FBP- and 86.9% of H-IR images. CONCLUSIONS: M-IR can provide significantly
      improved qualitative and quantitative image quality in prospectively gated
      coronary CTA using a low-tube-voltage.

PMID- 24873833
TI  - Assessment of neonatal growth in prematurely born infants.
AB  - The concept that adequate nutritional status and normal growth are important is
      well-accepted. How to assess the adequacy of nutrition and how to define
      appropriate growth remains an area of active debate. Our goal is to review how
      growth is assessed at birth and during the hospital stay of prematurely born
      infants, and to offer a standardized approach. 

PMID- 24873830
TI  - Efficient mutagenesis by Cas9 protein-mediated oligonucleotide insertion and
      large-scale assessment of single-guide RNAs.
AB  - The CRISPR/Cas9 system has been implemented in a variety of model organisms to
      mediate site-directed mutagenesis. A wide range of mutation rates has been
      reported, but at a limited number of genomic target sites. To uncover the rules
      that govern effective Cas9-mediated mutagenesis in zebrafish, we targeted over a
      hundred genomic loci for mutagenesis using a streamlined and cloning-free method.
      We generated mutations in 85% of target genes with mutation rates varying across
      several orders of magnitude, and identified sequence composition rules that
      influence mutagenesis. We increased rates of mutagenesis by implementing several
      novel approaches. The activities of poor or unsuccessful single-guide RNAs
      (sgRNAs) initiating with a 5' adenine were improved by rescuing 5' end
      homogeneity of the sgRNA. In some cases, direct injection of Cas9 protein/sgRNA
      complex further increased mutagenic activity. We also observed that low diversity
      of mutant alleles led to repeated failure to obtain frame-shift mutations. This
      limitation was overcome by knock-in of a stop codon cassette that ensured coding
      frame truncation. Our improved methods and detailed protocols make Cas9-mediated
      mutagenesis an attractive approach for labs of all sizes. 

PMID- 24873834
TI  - Linear growth and neurodevelopmental outcomes.
AB  - Despite advances in care, preterm infants exhibit disproportionate growth and
      neurodevelopmental delay attributable to both nutritional and nonnutritional
      factors. These infants have prolonged linear stunting and decreased fat-free mass
      compared with their term counterparts. These 2 metrics index organ growth and
      development (including the brain) and protein accretion. Protein, along with
      carbohydrates, fats, and zinc, plays key roles in brain development, and
      deficiencies can lead to linear growth failure, abnormalities in the growth
      hormone axis, and developmental delay. Optimization of nutrition, including
      protein intake, decreasing inflammatory episodes, and enhancing the growth
      hormone axis will likely improve long-term outcomes.

PMID- 24873835
TI  - Protein intake and neurodevelopmental outcomes.
AB  - There is a compelling body of literature that suggests that the provision of an
      inadequate amount of protein to preterm infants in the neonatal period has
      detrimental effects on the developing brain with the potential to result in long
      term, neurodevelopmental sequelae. Although a great deal of indirect evidence
      implies that the provision of adequate amounts of protein may be associated with
      better neurodevelopmental outcomes, there remains a paucity of direct evidence
      that would allow us to draw any final conclusions.

PMID- 24873837
TI  - Micronutrient requirements of high-risk infants.
AB  - Micronutrient requirements are well-established for healthy full-term infants.
      However, few such recommendations exist for high-risk infants, including full
      term infants with a variety of medical disorders or very preterm infants. Key
      micronutrients considered in this review are calcium, phosphorus, magnesium,
      iron, and zinc. The ongoing unresolved shortages, especially of intravenous forms
      of these minerals, remain a major problem. Considered are some aspects of how the
      nutrient shortages may be managed, recognizing the complexity and changing nature
      of the supply.

PMID- 24873838
TI  - Fatty acid requirements in preterm infants and their role in health and disease.
AB  - Challenges remain in optimizing the delivery of fatty acids to attain their
      nutritional and therapeutic benefits in neonatal health. In this review,
      knowledge about placental transfer of fatty acids to the developing fetus is
      summarized, the potential role and mechanisms of fatty acids in enhancing
      neonatal health and minimizing morbidities is outlined, the unique considerations
      for fatty acid delivery in the preterm population are defined, and the research
      questions are proposed that need to be addressed before new standards of care are
      adopted at the bedside for the provision of critical fatty acids to preterm
      infants.

PMID- 24873836
TI  - Complications associated with parenteral nutrition in the neonate.
AB  - Although parenteral nutrition (PN) is life-sustaining, it is associated with many
      complications including parenteral nutrition-associated liver disease (PNALD) and
      central line-associated bloodstream infections (CLASBIs), which carry a high
      morbidity and mortality and impose a burden on the health care system. Evidence
      has emerged that the dose and composition of intravenous lipid products may alter
      the incidence of PNALD. However, other patient and PN-related factors, such as
      prematurity, birth weight, and gastrointestinal anatomy and function, are
      important. To improve neonatal care, future research on optimizing the content of
      PN and decreasing the incidence IFALD and CLASBIs is required. 

PMID- 24873839
TI  - High-protein formulas: evidence for use in preterm infants.
AB  - Relatively high amounts of protein are required to achieve normal fractional
      protein synthetic rates during the late second through early third trimester of
      fetal growth. Once preterm infants achieve higher protein intakes for sustained
      periods, growth begins to approximate that of the normally growing fetus and long
      term neurodevelopmental outcomes are improved. Preterm formulas have been
      developed that are enriched in protein. This review discusses several factors
      when using standard preterm formulas and high-protein preterm formulas in the
      neonatal intensive care unit, with an emphasis on quantity and quality of enteral
      protein delivery and risks to insufficient and/or excess protein administration.

PMID- 24873840
TI  - Fortification of human milk in very low birth weight infants (VLBW <1500 g birth
      weight).
AB  - The American Academy of Pediatrics supports the feeding of human milk for all
      infants. Very-low-birth-weight and extremely low-birth-weight infants especially
      can benefit from the immune and neurodevelopmental effects of human milk.
      However, human milk alone is nutritionally inadequate for the rapid growth of the
      very-low-birth-weight infant during a critical window for brain development and
      requires fortification to meet current recommendations. There are a variety of
      products, devices, and strategies that can be used to fine tune nutritional
      support of these very vulnerable infants.

PMID- 24873842
TI  - Donor human milk for preterm infants: what it is, what it can do, and what still
      needs to be learned.
AB  - Donor human milk is a dietary intervention rapidly increasing in usage in the
      very low birth weight (VLBW) preterm population. Donor milk may decrease risk of
      necrotizing enterocolitis and improve neurodevelopmental outcomes in VLBW infants
      compared with formula diets. The exclusive human milk diet shows promise as an
      intervention to decrease risk of necrotizing enterocolitis compared with formula.
      Further research is needed to assess the impact of donor human milk on
      infectious, growth, and neurodevelopmental outcomes of VLBW infants, as well as
      the effect of milk fortifier choice (human vs bovine) on these outcomes.

PMID- 24873843
TI  - LCPUFAs as conditionally essential nutrients for very low birth weight and low
      birth weight infants: metabolic, functional, and clinical outcomes-how much is
      enough?
AB  - Preterm infants are denied the rapid accumulation of docosahexaenoic acid (DHA)
      occurring during the third trimester in utero. The potential benefit of long
      chain polyunsaturated fatty acids (LCPUFAs) has generated interest over the last
      3 decades. Early intervention trials assessed the effects of supplementing infant
      formulas lacking DHA with concentrations equivalent to LCPUFA in milk of women
      from Westernized societies, leading to the inclusion of LCPUFA by the year 2000.
      Recently attention has been on determining the optimal dose of DHA and on whether
      there is in advantage in matching the higher doses of late pregnancy.

PMID- 24873844
TI  - Post-discharge nutrition and the VLBW infant: To supplement or not supplement?: a
      review of the current evidence.
AB  - Due to advancements in neonatology, the survival of very-low-birth-weight
      infants, especially extremely low-birth-weight infants continues to rise. The
      goal of nutrition in these preterm infants is to match the intrauterine growth
      curves of the normally growing fetus. Despite this recommendation from the
      American Academy of Pediatrics Committee on Nutrition, neonatologists struggle
      daily to meet this goal, and as a result, postnatal growth failure and
      restriction are common. This article reviews post-discharge nutrition in the VLBW
      population, examining different types of post-discharge nutrition, current
      evidence, and future and remaining questions. In addition, recommendations are
      provided for post-discharge nutrition in this population. 

PMID- 24873841
TI  - Human breast milk and the gastrointestinal innate immune system.
AB  - The gastrointestinal (GI) tract is a large potential portal for multiple
      infectious agents to enter the human body. The GI system performs multiple
      functions as part of the neonate's innate immune system, providing critical
      defense during a vulnerable period. Multiple mechanisms and actions are enhanced
      by the presence of human breast milk. Bioactive factors found in human milk work
      together to create and maintain an optimal and healthy environment, allowing the
      intestines to deliver ideal nutrition to the host and afford protection by a
      variety of mechanisms.

PMID- 24873845
TI  - Neonatal nutrition.

PMID- 24873846
TI  - Our babies are what we feed them.

PMID- 24873847
TI  - Tissue repair in the embryonic rat spinal cord following exposure to N-ethyl-N
      nitrosourea.
AB  - The cytotoxic effects of N-ethyl-N-nitrosourea (ENU) and the potential for
      recovery from this damage in the developing rat spinal cord was investigated.
      Emphasis was placed on determining the severity and location of initial cell
      necrosis and the subsequent reorganizational changes in the damaged tissues.
      Pregnant rats were injected i.v. with a single dose of ENU (60 mg/kg) on one of
      days 12-16 of gestation. At 6, 12, 24 and 48 h post-injection one pregnant rat
      from each gestational stage was anesthetized, the embryos were removed, fixed and
      processed for embedding in paraplast or epon-araldite. Transverse sections from
      embryos killed at 6 h revealed extensive necrosis throughout the neuroepithelium
      in accordance with the temporal-spatial patterns of neurogenesis. At this dose
      level the post-mitotic neuroblasts appeared unaffected. Regeneration of the
      damaged neural tissue as defined by the restoration of the neuroepithelial cell
      layer and removal of necrotic debris proceeded quickly, and within 48 h a near
      normal cytoarchitecture was observed. The embryonic age at time of ENU injection
      had no apparent influence on the actual sequence of tissue repair in the spinal
      cords although the events were slightly delayed within embryos exposed to ENU on
      days 12 or 13 of gestation. 

PMID- 24873848
TI  - Ganglioside glycosyltransferase activities in the cerebral hemispheres from
      developing rat embryos.
AB  - The developmental patterns of three ganglioside glycosyltransferases were
      determined in the embryonic rat cerebral hemispheres from day 14 of gestation
      until birth. Considering the values of day 14 of gestation as 100%, the activity
      per MUg of DNA at birth of the CMP-NeuAc:GM3 sialosyltransferase decreased to
      40%, that of UDP-GalNAc:GM3 N-acetylgalactosaminyltransferase increased to 230%
      and that of UDP-Gal:GM2 galactosyltransferase showed minor variations. The
      changes in the activities of these enzymes correlated with the changes occurring
      in this embryonic period in the complexity of the oligosaccharide chain of
      gangliosides which result in a relative increase of gangliosides having the
      gangliotetraosyl backbone. 

PMID- 24873849
TI  - Hypomyelination and recovery of the myelin deficit in heterozygous jimpy mice.
AB  - The myelin content of the anterior commissure in female carriers of the jimpy
      gene (X(+)X(jp)) and in normal male mice (X(+)Y) was determined using
      morphometric methods. Young jimpy heterozygotes (X(+)X(jp)), 42-43 days old,
      exhibit a 33% reduction in myelin area fraction in the anterior limb of the
      anterior commissure. At older ages (? 145 days), the myelin area fraction in the
      heterozygotes is not different from control values in the anterior limb and the
      posterior limb of the anterior commissure. In comparing the young and old jimpy
      heterozygotes, a significant increase occurs in the myelin area fraction after 43
      days of age. The increase in the myelin area fraction in the anterior limb of the
      heterozygote may occur in response to the myelin deficit caused by the jimpy
      mutation and may involve the formation of new myelin. A further study of cellular
      interactions in the central nervous system of the jimpy heterozygote may provide
      new insight into mechanisms of myelin formation and remyelination. 

PMID- 24873850
TI  - Existence of [(3)H]serotonin binding sites in the rat spinal cord: A
      developmental study.
AB  - [(3)H]5-HT specific binding sites have been characterized in the rat spinal cord.
      Experimental conditions allowed us to study a single class of sites possibly
      related to the postsynaptic receptor for 5-HT. Binding constants (KD and Bmax)
      are described for adult and developing animals. No substantial changes in
      affinity were observed but the number of receptors increased from birth up to day
      20 postnatally, stabilizing thereafter. The developmental pattern of a
      presynaptic marker, tryptophan-5-hydroxylase, was similar to that of binding
      sites. 

PMID- 24873851
TI  - Regulation of the amino acid availability in the developing brain. No
      physiological significance of amino acid competition in experimental
      hyperphenylalaninemia.
AB  - Chronic experimental hyperphenylalaninemia in suckling rats causes a depletion of
      amino acids in the blood and in the brain, and an accumulation of amino acids in
      the peripheral tissues. The amino acid depletion in the blood is greater than
      that in the brain. The amino acid accumulating potency of all body tissues is
      increased by the excess of phenylalanine, most pronounced in the gut, least
      pronounced in the brain. All body tissues compete for the amino acids circulating
      in the blood. This competition is enhanced in hyperphenylalaninemia. The brain is
      at a disadvantage in the competition of the various body tissues for the amino
      acids available from the common pool. Brain tissue is increasingly depleted of
      amino acids as the accumulation of amino acids in the peripheral tissues is
      stimulated in hyperphenylalaninemia. The depletion of amino acids in the blood
      and the simultaneous rise of the free amino acid concentrations in the various
      developing tissues indicates tissue-specific shifts in the balance between
      protein synthesis and protein degradation in hyperphenylalaninemia. There is no
      indication that amino acid competition at the blood-brain barrier contributes
      importantly to the depletion of amino acids in the brain tissue in
      hyperphenylalaninemic rats. Instead, brain amino acid pools under in vivo steady
      state conditions appear to be primarily regulated by the rate of amino acid
      utilization by the peripheral tissues. 

PMID- 24873852
TI  - Ontogeny of glutamine synthetase in rat brain.
AB  - The developmental pattern of glutamine synthetase (GS) in rat brain has been
      studied with respect to that of the cells involved in the synthesis of the
      enzyme. GS activity is very low until day 13 after birth, rises sharply between
      days 13 and 15, and slowly thereafter. In contrast, more than half of the total
      number of protoplasmic astrocytes-the cells involved in synthesis of GS-are
      formed by day 12, following which the rate of proliferation declines
      considerably. GS is precociously inducible by cortisol in purified protoplasmic
      astrocytes, in organ cultures of 6-13 day rat brain and in the brains of
      cortisoladministered 12 day rats. These results and the temporal coincidence of
      the period of increase of GS with the onset of the function of adrenal cortex
      suggest that GS activity in the developing rat brain is under steroidal control. 

PMID- 24873853
TI  - Resistance to barbiturate is changed by developmental alteration of dopamine
      receptor sensitivity.
AB  - Adult rats whose dopamine receptor number was reduced via prenatal haloperidol
      exposure were less resistant than controls to pentobarbital narcosis. This
      altered resistance was functional (CNS) and not metabolic, as shown by
      pentobarbital brain levels. These results are consistent with our previous
      experiments, indicating that changes in the number of dopamine receptors may
      underlie relative susceptibility to barbiturates. 

PMID- 24873854
TI  - Pre- and postnatal development of the small intensely fluorescent cells in the
      rat superior cervical ganglion.
AB  - A fluorescence microscopical study has been performed in the pre- and postnatal
      development of the sympathetic superior cervical ganglion of Sprague-Dawley rat.
      Ganglia from 10.5- to 21.5-day-old embryos and newborn to 90-day-old postnatal
      rats were freeze-dried and the catecholamine-containing cells were demonstrated
      by formaldehyde-induced fluorescence. The first catecholamine-containing cells
      appeared on day 11.5 of gestation. The ganglia of 11.5- to 12.5-day-old embryos
      contained a continuous range of cells showing weak to bright fluorescence
      intensities. In the ganglia of 13.5- to 14.5-day-old embryos few solitary cells
      or small groups of cells showing bright fluorescence were discernible among
      weakly fluorescent developing principal nerve cells. The cell numbers of both
      types markedly increased during the prenatal period while the mean diameter of
      the brightly fluorescent cells significantly decreased. In the late prenatal
      ganglia clusters were observed in which a large brightly fluorescent cell was
      surrounded by other intensely fluorescent cells of various sizes. There were
      about 300 small intensely fluorescent (SIF) cells in the ganglia of newborn rats.
      This number decreased by about 50% during postnatal week 1 and again increased
      during postnatal week 4 reaching the adult value of about 500 cells/ganglion.
      During the postnatal development the SIF cells formed clusters, the largest of
      which contained several hundred cells. Occurrence of large intensely fluorescent
      cells during a limited period suggests that this cell type represents a
      transitional form. It is possible that in the rat the primitive sympathetic cells
      continue their development along two lines: some cells remain weakly fluorescent
      and give rise to the principal nerve cells, and others accumulate
      catecholamine(s) and are transformed, possibly after mitotic divisions, into
      smaller brightly fluorescent cells which mature into SIF cells late postnatally. 

PMID- 24873855
TI  - Sex difference in dendritic development of the sexually dimorphic nucleus of the
      preoptic area in the rat.
AB  - Sex differences in the growth and dendritic development of neurons in the
      sexually dimorphic nucleus of the preoptic area were examined with quantitative
      Golgi techniques during early postnatal life in rats. Neuronal size and dendritic
      extent were found to increase more in males than in females during the first 10
      postnatal days, while the numbers of primary and terminal dendrites were similar
      in the two sexes. The onset of greater dendritic growth in males occurs just
      after the volume of the nucleus begins to exhibit sexual dimorphism, between 24
      and 26 days after fertilization. Growth of dendrites in this region may be
      related to the presence of sex hormones during the critical period of sexual
      brain differentiation. 

PMID- 24873856
TI  - Association of laminin and other basement membrane components with regions of
      high acetylcholine receptor density on cultured myotubes.
AB  - The distribution of immunoreactivity to basement membrane components in cultures
      of rat skeletal myotubes was compared to acetylcholine receptor distribution by
      fluorescence microscopy. Laminin occurred in patches on the myotube surface, and
      most laminin patches coincided or overlapped with acetylcholine receptor
      aggregates. Almost all receptor aggregates coincided with laminin patches. Most
      of the heparan sulfate proteoglycan and fibronectin was associated with non
      muscle cells, but some patches coincided with receptor aggregates on myotubes. In
      cultures treated with l-ascorbate, collagen types IV and V covered much of the
      myotube surface and receptor aggregates often coincided with intense collagen
      patches. When receptor aggregation was induced by treatment of cultures with
      soluble neural factors, the newly formed receptor aggregates coincided with
      laminin patches. The results suggest that each of the basement membrane
      components studied has a distinct distribution pattern in primary rat muscle cell
      cultures. The striking association of laminin immunoreactivity with receptor
      aggregates, together with the enhancement of receptor aggregation by laminin
      reported previously (Vogel et al., J. Neurosci. 3, 1058-1068, 1983) suggests that
      laminin could have a role in the organization of acetylcholine receptors on
      developing muscle fibers. 

PMID- 24873857
TI  - Editorial.

PMID- 24873858
TI  - Gas-phase structures of sterically crowded disilanes studied by electron
      diffraction and quantum chemical methods: 1,1,2,2
      tetrakis(trimethylsilyl)disilane and 1,1,2,2
      tetrakis(trimethylsilyl)dimethyldisilane.
AB  - The gas-phase structures of the disilanes 1,1,2,2
      tetrakis(trimethylsilyl)disilane [(Me3Si)2HSiSiH(SiMe3)2] (1) and 1,1,2,2
      tetrakis(trimethylsilyl)dimethyldisilane [(Me3Si)2MeSiSiMe(SiMe3)2] (2) have been
      determined by density functional theoretical calculations and by gas electron
      diffraction (GED) employing the SARACEN method. For each of 1 and 2 DFT
      calculations revealed four C2-symmetric conformers occupying minima on the
      respective potential-energy surfaces; three conformers were estimated to be
      present in sufficient quantities to be taken into account when fitting the GED
      data. For (Me3Si)2RSiSiR(SiMe3)2 [R = H (1), CH3 (2)] the lowest energy
      conformers were found by GED to have RSiSiR dihedral angles of 87.7(17) degrees 
      for 1 and -47.0(6) degrees  for 2. For each of 1 and 2 the presence of bulky and
      flexible trimethylsilyl groups dictates many aspects of the geometric structures
      in the gas phase, with the molecules often adopting structures that reduce steric
      strain. 

PMID- 24873859
TI  - A multiplex high-throughput gene expression assay to simultaneously detect
      disease and functional markers in induced pluripotent stem cell-derived retinal
      pigment epithelium.
AB  - There is continuing interest in the development of lineage-specific cells from
      induced pluripotent stem (iPS) cells for use in cell therapies and drug
      discovery. Although in most cases differentiated cells show features of the
      desired lineage, they retain fetal gene expression and do not fully mature into
      "adult-like" cells. Such cells may not serve as an effective therapy because,
      once implanted, immature cells pose the risk of uncontrolled growth. Therefore,
      there is a need to optimize lineage-specific stem cell differentiation protocols
      to produce cells that no longer express fetal genes and have attained "adult
      like" phenotypes. Toward that goal, it is critical to develop assays that
      simultaneously measure cell function and disease markers in high-throughput
      format. Here, we use a multiplex high-throughput gene expression assay that
      simultaneously detects endogenous expression of multiple developmental,
      functional, and disease markers in iPS cell-derived retinal pigment epithelium
      (RPE). We optimized protocols to differentiate iPS cell-derived RPE that was then
      grown in 96- and 384-well plates. As a proof of principle, we demonstrate
      differential expression of eight genes in iPS cells, iPS cell-derived RPE at two
      different differentiation stages, and primary human RPE using this multiplex
      assay. The data obtained from the multiplex gene expression assay are
      significantly correlated with standard quantitative reverse transcription
      polymerase chain reaction-based measurements, confirming the ability of this high
      throughput assay to measure relevant gene expression changes. This assay provides
      the basis to screen for compounds that improve RPE function and maturation and
      target disease pathways, thus providing the basis for effective treatments of
      several retinal degenerative diseases. 

PMID- 24873860
TI  - Multicolor staining of globin subtypes reveals impaired globin switching during
      erythropoiesis in human pluripotent stem cells.
AB  - Adult hemoglobin composed of alpha- and beta-globin reflects a change from
      expression of embryonic epsilon- and fetal gamma-globin to adult beta-globin in
      human erythroid cells, so-called globin switching. Human pluripotent stem cells
      (hPSCs) are a potential source for in vitro erythrocyte production, but they show
      prominent expression of gamma-globin with little beta-globin expression, which
      indicates incomplete globin switching. To examine the mechanism of this impaired
      globin switching, we optimized multicolor flow cytometry to simultaneously follow
      expression of different globin subtypes using different immunofluorescent probes.
      This enabled us to detect upregulation of beta-globin and the corresponding
      silencing of gamma-globin at the single-cell level during cord blood CD34(+) cell
      derived erythropoiesis, examined as an endogenous control. Using this approach,
      we initially characterized the heterogeneous beta-globin expression in
      erythroblasts from several hPSC clones and confirmed the predominant expression
      of gamma-globin. These hPSC-derived erythroid cells also displayed reduced
      expression of BCL11A-L. However, doxycycline-induced overexpression of BCL11A-L
      in selected hPSCs promoted gamma-globin silencing. These results strongly suggest
      that impaired gamma-globin silencing is associated with downregulated BCL11A-L in
      hPSC-derived erythroblasts and that multicolor staining of globin subtypes is an
      effective approach to studying globin switching in vitro. 

PMID- 24873862
TI  - Contributions of individual muscles to the sagittal- and frontal-plane angular
      accelerations of the trunk in walking.
AB  - This study was conducted to analyze the unimpaired control of the trunk during
      walking. Studying the unimpaired control of the trunk reveals characteristics of
      good control. These characteristics can be pursued in the rehabilitation of
      impaired control. Impaired control of the trunk during walking is associated with
      aging and many movement disorders. This is a concern as it is considered to
      increase fall risk. Muscles that contribute to the trunk control in normal
      walking may also contribute to it under perturbation circumstances, attempting to
      prevent an impending fall. Knowledge of such muscles can be used to rehabilitate
      impaired control of the trunk. Here, angular accelerations of the trunk induced
      by individual muscles, in the sagittal and frontal planes, were calculated using
      3D muscle-driven simulations of seven young healthy subjects walking at free
      speed. Analysis of the simulations demonstrated that the abdominal and back
      muscles displayed large contributions throughout the gait cycle both in the
      sagittal and frontal planes. Proximal lower-limb muscles contributed more than
      distal muscles in the sagittal plane, while both proximal and distal muscles
      showed large contributions in the frontal plane. Along with the stance-limb
      muscles, the swing-limb muscles also exhibited considerable contribution. The
      gluteus medius was found to be an important individual frontal-plane control
      muscle; enhancing its function in pathologies could ameliorate gait by
      attenuating trunk sway. In addition, since gravity appreciably accelerated the
      trunk in the frontal plane, it may engender excessive trunk sway in pathologies. 

PMID- 24873861
TI  - Concise review: new frontiers in microRNA-based tissue regeneration.
AB  - In recent years, the role of miRNAs in post-transcriptional gene regulation has
      come to the fore with strong evidence to indicate an important role for microRNAs
      (miRNAs) in the regulation of a wide range of fundamental biological processes.
      Notably, this includes the regulation of both endogenous tissue repair mechanisms
      and the growth and differentiation of stem cells (both adult and pluripotent). As
      a result, manipulation of miRNA signaling holds great promise for regenerative
      medicine, which aims to harness either endogenous or implanted cells to promote
      tissue repair. However, to fully realize this potential, it will be necessary to
      combine advances in our biological understanding with new technologies that allow
      precise spatiotemporal modulation of specific miRNA candidates. In this review,
      we highlight the role of miRNAs in tissue regeneration, discuss key challenges in
      translating this knowledge to the clinic, and outline recent technological
      advances that aim to address these issues. By combining a comprehensive knowledge
      of miRNA biology with cutting-edge delivery technologies, it is clear that miRNAs
      hold significant promise for tissue regenerative therapies in the future. 

PMID- 24873863
TI  - Biomechanical modeling to prevent ischial pressure ulcers.
AB  - With 300,000 paraplegic persons only in France, ischial pressure ulcers represent
      a major public health issue. They result from the buttocks' soft tissues
      compression by the bony prominences. Unfortunately, the current clinical
      techniques, with - in the best case - embedded pressure sensor mats, are
      insufficient to prevent them because most are due to high internal strains which
      can occur even with low pressures at the skin surface. Therefore, improving
      prevention requires using a biomechanical model to estimate internal strains from
      skin surface pressures. However, the buttocks' soft tissues' stiffness is still
      unknown. This paper provides a stiffness sensitivity analysis using a finite
      element model. Different layers with distinct Neo Hookean materials simulate the
      skin, fat and muscles. With Young moduli in the range [100-500 kPa], [25-35 kPa],
      and [80-140 kPa] for the skin, fat, and muscles, respectively, maximum internal
      strains reach realistic 50 to 60% values. The fat and muscle stiffnesses have an
      important influence on the strain variations, while skin stiffness is less
      influent. Simulating different sitting postures and changing the muscle thickness
      also result in a variation in the internal strains.

PMID- 24873865
TI  - War leaves an enduring legacy in combatants' lives.
AB  - The memory of combat experience endures in World War II veterans. As veterans
      age, traumatic memory that previously may have been suppressed in the busyness of
      family and everyday life can re-emerge. Combat stress may affect not only the
      veterans, but also those people closely associated with them. Interviews were
      conducted with World War II veteran aircrew, wives, children, grandchildren,
      siblings, and friends to examine the impact of combat experience on the veterans
      and the family across the life course from the perspectives of the various
      participants. The combat experience significantly affected the life course of
      most.

PMID- 24873864
TI  - [Consensus guidelines for the management of community acquired pneumonia in the
      elderly patient].
AB  - The incidence of community-acquired pneumonia increases with age and is
      associated with an elevated morbidity and mortality due to the physiological
      changes associated with aging and a greater presence of chronic disease. Taking
      into account the importance of this disease from an epidemiological and
      prognostic point of view, and the enormous heterogeneity described in the
      clinical management of the elderly, we believe a specific consensus document
      regarding this patient profile is necessary. The purpose of the present work was
      to perform a review of the evidence related to the risk factors for the etiology,
      the clinical presentation, the management and the treatment of community-acquired
      pneumonia in elderly patients with the aim of producing a series of specific
      recommendations based on critical analysis of the literature. This document is
      the result of the collaboration of different specialists representing the Spanish
      Society of Emergency Medicine and Emergency Care (SEMES), the Spanish Society of
      Geriatrics and Gerontology (SEGG), the Spanish Society of Chemotherapy (SEQ), the
      Spanish Society of Internal Medicine (SEMI), the Spanish Society of Respiratory
      Medicine and Thoracic Surgery (SEPAR), Spanish Society of Home Hospitalization
      (SEHAD) and the Spanish Society of Infectious Disease and Clinical Microbiology
      (SEIMC). 

PMID- 24873870
TI  - Effect of almond processing on levels and distribution of aflatoxins in finished
      products and byproducts.
AB  - The fate of aflatoxins during processing of contaminated almonds into nougat,
      pastries, and almond syrup was evaluated by testing the effect of each processing
      step (blanching, peeling, roasting, caramelization, cooking, and water infusion)
      on the distribution and levels of aflatoxins. Blanching and peeling did not
      reduce total aflatoxins that were distributed between peeled almonds (90-93%) and
      skins (7-10%). Roasting of peeled almonds reduced up to 50% of aflatoxins. Up to
      70% reduction of aflatoxins was observed during preparation and cooking of almond
      nougat in caramelized sugar. Aflatoxins were substantially stable during
      preparation and cooking of almond pastries. The whole process of almond syrup
      preparation produced a marked increase of total aflatoxins (up to 270%) that were
      distributed between syrup (18-25%) and spent almonds (75-82%). The increase of
      total aflatoxins was probably due to the activation of almond enzymes during the
      infusion step that released free aflatoxins from masked aflatoxins. 

PMID- 24873871
TI  - Assessment of Frizzled 6 membrane mobility by FRAP supports G protein coupling
      and reveals WNT-Frizzled selectivity.
AB  - The WNT receptors of the Frizzled family comprise ten mammalian isoforms, bind
      WNT proteins and mediate downstream signaling to regulate stem cell fate,
      neuronal differentiation, cell survival and more. WNT-induced signaling pathways
      are either beta-catenin-dependent or -independent, thereby dividing the 19
      mammalian WNT proteins into two groups. So far hardly any quantitative,
      pharmacological information is available about WNT-FZD interaction profiles,
      affinities or mechanisms of signaling specification through distinct WNT/FZD
      pairings. This lack of knowledge originates from difficulties with WNT
      purification and a lack of suitable assays, such as ligand binding assays and FZD
      activity readouts. In order to minimize this gap, we employ fluorescence recovery
      after photobleaching (FRAP) to investigate WNT effects on the lateral mobility of
      FZD6-GFP in living cells. Pharmacological uncoupling of heterotrimeric G proteins
      by pertussis toxin and N-ethylmaleimide argues that changes in FZD6 mobility are
      related to putative precoupling of heterotrimeric Gi/o proteins to FZD6. We show
      that recombinant WNT-1, -2, 3A, -4, -5A, -7A, -9B and -10B affect FZD6 surface
      mobility and thus act on this receptor. WNT-5B and WNT-11, on the other hand,
      have no effect on FZD6 mobility and we conclude that they do not act through
      FZD6. We introduce here a novel way to assess WNT-FZD interaction by live cell
      imaging allowing further mapping of WNT-FZD interactions and challenging previous
      experimental limitations. Increased understanding of WNT-FZD selectivity provides
      important insight into the biological function of this crucial signaling system
      with importance in developmental biology, stem cell regulation oncogenesis, and
      human disease.

PMID- 24873873
TI  - Inhaler devices in asthma and COPD--an assessment of inhaler technique and
      patient preferences.
AB  - BACKGROUND: Incorrect use of inhaler devices remains an obstacle for respiratory
      diseases management. We aimed to evaluate the frequency of inhaler technique
      errors; to determine the devices perceived as the easiest and favourite to use;
      to study the association of device type, demographics and patient preferences
      with inhaler technique (IT). METHODS: Cross-sectional assessment of 301 adults,
      with asthma (194) or chronic pulmonary obstructive disease, undergoing treatment
      with Aerolizer(r), Autohaler(r), Breezehaler(r), Diskus(r), Handihaler(r), MDI
      without spacer, Miat-haler(r), Novolizer(r), Respimat(r) and/or Turbohaler(r).
      Patients completed self-assessment questionnaires and face-to-face interview,
      with demonstration of inhaler technique. The rate of wrong steps (number of wrong
      steps / number of total steps; RWS) was the primary outcome. Adjusted odds ratio
      (aOR) (95% confidence intervals [CI]) for presenting >=1 IT errors were computed.
      RESULTS: From the 464 inhaler technique performances, the median RWS was 18%.
      Turbohaler(r) (21%) and Diskus(r) (19%) were chosen as easiest and Novolizer(r)
      (18%), Diskus(r) (18%), Turbohaler(r) (17%) as favourite for daily use. Females
      (aOR 2.68 [95% CI 1.55-4.65]; vs. males], patients with >64 yr (aOR 2.73 [95% CI
      1.15-6.48]; vs <45 yr) and patients using Aerolizer(r) or Handihaler(r) (aOR 3.24
      [95% CI 1.13-9.32] and aOR 3.71 [95% CI 1.38-10.2], respectively) were more
      likely to perform IT errors; otherwise, no association was found, including with
      using the favourite device (aOR 1.43 [95% CI 0.84-2.42]). CONCLUSION: The
      frequency of inhaler technique errors was high and no device was clearly
      preferred over the others. Using the preferred inhaler device was not associated
      with less errors.

PMID- 24873872
TI  - Single center experience in patients with unilateral multicystic dysplastic
      kidney.
AB  - OBJECTIVE: To determine the clinical features, long-term outcomes, and additional
      urological anomalies of patients treated for multicystic dysplastic kidney (MDK).
      MATERIALS AND METHODS: Patients with MDK who were followed between January 2004
      and October 2012 were reviewed retrospectively. Demographic, clinical,
      laboratory, and radiological data were evaluated. RESULTS: A total of 68 patients
      with MDK were followed for a mean period of 46.8 +/- 32.4 months. MDK was
      detected by antenatal ultrasound in 64 (94.1%) of the patients. Ten patients had
      (14.7%) additional urological anomalies in contralateral kidney. Vesicoureteral
      reflux was found in five patients (7.3%). Other urological anomalies were
      megaureter (two), cortical renal cyst (two), ureteropelvic junction obstruction
      (one), and renal ectopy (one). Urinary tract infection was detected in 14 (20.5%)
      patients. Four (5.9%) patients had hypertension. Compensatory hypertrophy was
      detected in 29 (42.6%) patients. Eight (11.8%) of these 29 patients had
      glomerular hyperfiltration and three (4.4%) of these eight patients also had
      proteinuria. Follow-up ultrasound revealed complete involution in 19 (35.8%)
      patients. Nephrectomy was performed in 15 (22.0%) patients. Indications of
      nephrectomy were, recurrent urinary infection (four), hypertension (three),
      ureterocele (two), renal calculi (one), flank pain (one), hematuria (one),
      persistent large cystic kidney (three), and atypical US findings (two).
      CONCLUSION: In patients with MDK, depending on the clinical, laboratory, and
      radiological findings, appropriate timing of operation by multidisciplinary
      approach is important for early detection and treatment of any possible
      complications.

PMID- 24873874
TI  - Evaluating the technique of using inhalation device in COPD and bronchial asthma
      patients.
AB  - BACKGROUND: In asthma management, poor handling of inhalation devices and wrong
      inhalation technique are associated with decreased medication delivery and poor
      disease control. The key to overcome the drawbacks in inhalation technique is to
      make patients familiar with issues related to correct use and performance of
      these medical devices. The objective of this study was to evaluate and analyse
      technique of use of the inhalation device used by patients of COPD and Bronchial
      Asthma. METHODS: A total of 300 cases of BA or COPD patients using different
      types of inhalation devices were included in this observational study. Data were
      captured using a proforma and were analysed using SPSS version 15.0. RESULT: Out
      of total 300 enrolled patients, 247 (82.3%) made at least one error. Maximum
      errors observed in subjects using MDI (94.3%), followed by DPI (82.3%), MDI with
      Spacer (78%) while Nebulizer users (70%) made least number of errors (p = 0.005).
      Illiterate patients showed 95.2% error while post-graduate and professionals
      showed 33.3%. This difference was statistically significant (p < 0.001). Self
      educated patients committed 100% error, while those trained by a doctor made
      56.3% error. CONCLUSION: Majority of patients using inhalation devices made
      errors while using the device. Proper education to patients on correct usage may
      not only improve control of the symptoms of the disease but might also allow dose
      reduction in long term.

PMID- 24873876
TI  - Novel aspects of RNA regulation in Staphylococcus aureus.
AB  - A plethora of RNAs with regulatory functions has been discovered in many non
      pathogenic and pathogenic bacteria. In Staphylococcus aureus, recent findings
      show that a large variety of RNAs control target gene expression by diverse
      mechanisms and many of them are expressed in response to specific internal or
      external signals. These RNAs comprise trans-acting RNAs, which regulate gene
      expression through binding with mRNAs, and cis-acting regulatory regions of
      mRNAs. Some of them possess multiple functions and encode small but functional
      peptides. In this review, we will present several examples of RNAs regulating
      pathogenesis, antibiotic resistance, and host-pathogen interactions and will
      illustrate how regulatory proteins and RNAs form complex regulatory circuits to
      express the virulence factors in a dynamic manner. 

PMID- 24873877
TI  - Renaissance of mammalian endogenous RNAi.
AB  - RNA interference (RNAi) denotes sequence-specific mRNA degradation induced by
      long double-stranded RNA (dsRNA). RNAi is an ancient eukaryotic defense mechanism
      against viruses and mobile elements. In mammals, endogenous RNAi was outstripped
      during evolution by the current innate and acquired immunity. The RNAi apparatus,
      which remains essentially intact, serves mostly the microRNA pathway, which
      regulates endogenous gene expression. Remarkably, several recent publications
      brought the mammalian endogenous RNAi pathway back into the spotlight. Here, I
      will provide an up-to-date review of the mammalian endogenous RNAi pathway with a
      focus on its defensive role and overlaps with miRNA and piRNA pathways. 

PMID- 24873878
TI  - Arthritis susceptibility and the gut microbiome.
AB  - Rheumatoid arthritis (RA) is an autoimmune disease with unknown etiology though
      both genetic and environmental factors have been suggested to be involved in its
      pathogenesis. While infections and other environmental factors (e.g. smoking)
      have been studied extensively and show some association, a direct link between
      all the factors has been difficult to prove. With the recent advances in
      technology, it has become possible to sequence the commensals that are residing
      in our gut. The gut microbiome may provide the missing link to this puzzle and
      help solve the mystery of many leaky gut syndromes. The gut commensals are
      involved in maintaining host immune homeostasis and function suggesting that they
      might be critical in altering the immune system, which leads to autoimmune
      diseases like RA. Mouse models support the role of the gut microbiota in
      predisposition to RA. If that is true, the power of gut-derived commensal can be
      harnessed to our benefit by generating a biomarker profile along with genetic
      factors to define individuals at risk and by altering the gut microbial
      composition using various means. 

PMID- 24873879
TI  - Effect of microRNA-145 on IL-1beta-induced cartilage degradation in human
      chondrocytes.
AB  - MicroRNA-145 has been shown to regulate chondrocyte homeostasis. It seems that
      miR-145 is implicated in cartilage dysfunction in Osteoarthritis (OA). However,
      the functional role of miR-145 in interleukin-1 beta (IL-1beta)-induced
      extracellular matrix (ECM) degradation of OA cartilage has never been clarified.
      Here, we show that miR-145 expression increased in OA chondrocytes and in
      response to IL-1beta stimulation. We confirm that mothers against decapentaplegic
      homolog 3 (Smad3), a key factor in maintaining chondrocyte homeostasis, is
      directly regulated by miR-145. Modulation of miR-145 affects the expression of
      Smad3 causing a change of its downstream target gene expression as well as IL
      1beta-induced ECM degradation in OA chondrocytes. This indicates that miR-145
      contributes to impaired ECM in OA cartilage probably in part via targeting Smad3.

PMID- 24873880
TI  - Poly(A) polymerase (PAP) diversity in gene expression--star-PAP vs canonical PAP.
AB  - Almost all eukaryotic mRNAs acquire a poly(A) tail at the 3'-end by a concerted
      RNA processing event: cleavage and polyadenylation. The canonical PAP, PAPalpha,
      was considered the only nuclear PAP involved in general polyadenylation of mRNAs.
      A phosphoinositide-modulated nuclear PAP, Star-PAP, was then reported to regulate
      a select set of mRNAs in the cell. In addition, several non-canonical PAPs have
      been identified with diverse cellular functions. Further, canonical PAP itself
      exists in multiple isoforms thus illustrating the diversity of PAPs. In this
      review, we compare two nuclear PAPs, Star-PAP and PAPalpha with a general
      overview of PAP diversity in the cell. Emerging evidence suggests distinct niches
      of target pre-mRNAs for the two PAPs and that modulation of these PAPs regulates
      distinct cellular functions. 

PMID- 24873882
TI  - Dynamics and dispensability of variant-specific histone H1 Lys-26/Ser-27 and Thr
      165 post-translational modifications.
AB  - In mammals, the linker histone H1, involved in DNA packaging into chromatin, is
      represented by a family of variants. H1 tails undergo post-translational
      modifications (PTMs) that can be detected by mass spectrometry. We developed
      antibodies to analyze several of these as yet unexplored PTMs including the
      combination of H1.4 K26 acetylation or trimethylation and S27 phosphorylation.
      H1.2-T165 phosphorylation was detected at S and G2/M phases of the cell cycle and
      was dispensable for chromatin binding and cell proliferation; while the H1.4-K26
      residue was essential for proper cell cycle progression. We conclude that histone
      H1 PTMs are dynamic over the cell cycle and that the recognition of modified
      lysines may be affected by phosphorylation of adjacent residues. 

PMID- 24873883
TI  - An open trial of videoconference-mediated exposure and ritual prevention for
      obsessive-compulsive disorder.
AB  - The gold-standard treatment for OCD is exposure and ritual prevention (ERP), yet
      despite its well-established efficacy, only a small percentage of OCD patients
      have access to this treatment. Remote treatments (e.g., videoconferencing) are
      becoming increasingly popular avenues for treatment delivery and show promise in
      increasing patient access to evidence-based mental health care. The current pilot
      study utilized an open trial to examine the feasibility and preliminary efficacy
      of videoconference-mediated, twice weekly, ERP for adults (n=15) with OCD.
      Results revealed that ERP was associated with significant improvements in OCD
      symptoms and large within-group effect sizes. Among the 10 individuals who
      completed a 3-month follow-up assessment, 30% of participants no longer met DSM
      IV-TR criteria for OCD and 80% of participants were rated as very much or much
      improved on the CGI. This study adds to the growing body of literature suggesting
      that videoconference-based interventions are viable alternatives to face-to-face
      treatment. 

PMID- 24873884
TI  - "But it might be a heart attack": intolerance of uncertainty and panic disorder
      symptoms.
AB  - Panic disorder models describe interactions between feared anxiety-related
      physical sensations (i.e., anxiety sensitivity; AS) and catastrophic
      interpretations therein. Intolerance of uncertainty (IU) has been implicated as
      necessary for catastrophic interpretations in community samples. The current
      study examined relationships between IU, AS, and panic disorder symptoms in a
      clinical sample. Participants had a principal diagnosis of panic disorder, with
      or without agoraphobia (n=132; 66% women). IU was expected to account for
      significant variance in panic symptoms controlling for AS. AS was expected to
      mediate the relationship between IU and panic symptoms, whereas IU was expected
      to moderate the relationship between AS and panic symptoms. Hierarchical linear
      regressions indicated that IU accounted for significant unique variance in panic
      symptoms relative to AS, with comparable part correlations. Mediation and
      moderation models were also tested and suggested direct and indirect effects of
      IU on panic symptoms through AS; however, an interaction effect was not
      supported. The current cross-sectional evidence supports a role for IU in panic
      symptoms, independent of AS. 

PMID- 24873881
TI  - Steering tumor progression through the transcriptional response to growth factors
      and stroma.
AB  - Tumor progression can be understood as a collaborative effort of mutations and
      growth factors, which propels cell proliferation and matrix invasion, and also
      enables evasion of drug-induced apoptosis. Concentrating on EGFR, we discuss
      downstream signaling and the initiation of transcriptional events in response to
      growth factors. Specifically, we portray a wave-like program, which initiates by
      rapid disappearance of two-dozen microRNAs, followed by an abrupt rise of
      immediate early genes (IEGs), relatively short transcripts encoding
      transcriptional regulators. Concurrent with the fall of IEGs, some 30-60 min
      after stimulation, a larger group, the delayed early genes, is up-regulated and
      its own fall overlaps the rise of the final wave of late response genes. This
      late wave persists and determines long-term phenotype acquisition, such as
      invasiveness. Key regulatory steps in the orderly response to growth factors
      provide a trove of potential oncogenes and tumor suppressors.

PMID- 24873885
TI  - Mild to severe social fears: ranking types of feared social situations using item
      response theory.
AB  - Social anxiety disorder is one of the most common mental disorders, and is
      associated with long term impairment, distress and vulnerability to secondary
      disorders. Certain types of social fears are more common than others, with public
      speaking fears typically the most prevalent in epidemiological surveys. The
      distinction between performance- and interaction-based fears has been the focus
      of long-standing debate in the literature, with evidence performance-based fears
      may reflect more mild presentations of social anxiety. This study aims to
      explicitly test whether different types of social fears differ in underlying
      social anxiety severity using item response theory techniques. Different types of
      social fears were assessed using items from three different structured diagnostic
      interviews in four different epidemiological surveys in the United States
      (n=2261, n=5411) and Australia (n=1845, n=1497); and ranked using 2-parameter
      logistic item response theory models. Overall, patterns of underlying severity
      indicated by different fears were consistent across the four samples with items
      functioning across a range of social anxiety. Public performance fears and
      speaking at meetings/classes indicated the lowest levels of social anxiety, with
      increasing severity indicated by situations such as being assertive or attending
      parties. Fears of using public bathrooms or eating, drinking or writing in public
      reflected the highest levels of social anxiety. Understanding differences in the
      underlying severity of different types of social fears has important implications
      for the underlying structure of social anxiety, and may also enhance the delivery
      of social anxiety treatment at a population level. 

PMID- 24873886
TI  - The role of antigen specificity in the binding of murine monoclonal anti-DNA
      antibodies to microparticles from apoptotic cells.
AB  - Antibodies to DNA (anti-DNA) are the serological hallmark of systemic lupus
      erythematosus and markers of underlying immune system disturbances. These
      antibodies bind to both single-stranded and double-stranded DNA, mediating
      pathogenesis by forming immune complexes. As shown recently, DNA in blood exists
      in both free and particulate forms, with DNA representing an important component
      of microparticles. Microparticles are membrane-bound vesicles containing nuclear
      molecules, released by membrane blebbing during cell death and activation. A
      panel of monoclonal NZB/NZW F1 anti-DNA antibodies was tested for binding to
      microparticles generated from apoptotic THP-1 and Jurkat cells. These studies
      showed that only certain anti-DNA antibodies in the panel, specific for double
      stranded DNA, bound to microparticles. Binding to particles was reduced by
      soluble DNA or DNase treatment. Together, these results indicate that particle
      binding is a feature of only certain anti-DNA antibodies, reflecting
      immunochemical properties of the antibodies and the nature of the exposed DNA
      antigens. 

PMID- 24873887
TI  - Label free cell-tracking and division detection based on 2D time-lapse images for
      lineage analysis of early embryo development.
AB  - In this paper we report a database and a series of techniques related to the
      problem of tracking cells, and detecting their divisions, in time-lapse movies of
      mammalian embryos. Our contributions are (1) a method for counting embryos in a
      well, and cropping each individual embryo across frames, to create individual
      movies for cell tracking; (2) a semi-automated method for cell tracking that
      works up to the 8-cell stage, along with a software implementation available to
      the public (this software was used to build the reported database); (3) an
      algorithm for automatic tracking up to the 4-cell stage, based on histograms of
      mirror symmetry coefficients captured using wavelets; (4) a cell-tracking
      database containing 100 annotated examples of mammalian embryos up to the 8-cell
      stage; and (5) statistical analysis of various timing distributions obtained from
      those examples. 

PMID- 24873888
TI  - Worry as an adaptive avoidance strategy in healthy controls but not in
      pathological worriers.
AB  - The cognitive avoidance model of worry assumes that worry has the adaptive
      function to keep under control the physiological arousal associated with anxiety.
      This study aimed to test this model by the use of a fear induction paradigm in
      both pathological and healthy individuals. Thirty-one pathological worriers and
      36 healthy controls accepted to be exposed to a fear induction paradigm (white
      noise) during three experimental conditions: worry, distraction, and reappraisal.
      Skin conductance (SCR) and heart rate variability (HRV) were measured as indices
      of sympathetic and parasympathetic nervous system functioning. Worriers showed
      increased sympathetic and decreased parasympathetic activation during the worry
      condition compared to non-worriers. There were no differences between groups for
      the distraction and reappraisal conditions. SCRs to the white noises during worry
      were higher in worriers versus controls throughout the entire worry period.
      Intolerance of uncertainty - but not metacognitive beliefs about worry - was a
      significant moderator of the relationship between worry and LF/HF-HRV in
      pathological worriers. Results support the cognitive avoidance model in healthy
      controls, suggesting that worry is no longer a functional attitude when it
      becomes the default/automatic and pathological response. 

PMID- 24873889
TI  - A comparative study of progressive versus successive spectrophotometric
      resolution techniques applied for pharmaceutical ternary mixtures.
AB  - This work represents a comparative study of a novel progressive
      spectrophotometric resolution technique namely, amplitude center method (ACM),
      versus the well-established successive spectrophotometric resolution techniques
      namely; successive derivative subtraction (SDS); successive derivative of ratio
      spectra (SDR) and mean centering of ratio spectra (MCR). All the proposed
      spectrophotometric techniques consist of several consecutive steps utilizing
      ratio and/or derivative spectra. The novel amplitude center method (ACM) can be
      used for the determination of ternary mixtures using single divisor where the
      concentrations of the components are determined through progressive manipulation
      performed on the same ratio spectrum. Those methods were applied for the analysis
      of the ternary mixture of chloramphenicol (CHL), dexamethasone sodium phosphate
      (DXM) and tetryzoline hydrochloride (TZH) in eye drops in the presence of
      benzalkonium chloride as a preservative. The proposed methods were checked using
      laboratory-prepared mixtures and were successfully applied for the analysis of
      pharmaceutical formulation containing the cited drugs. The proposed methods were
      validated according to the ICH guidelines. A comparative study was conducted
      between those methods regarding simplicity, limitation and sensitivity. The
      obtained results were statistically compared with those obtained from the
      official BP methods, showing no significant difference with respect to accuracy
      and precision. 

PMID- 24873890
TI  - DFT computational analysis of piracetam.
AB  - Density functional theory calculation with B3LYP using 6-31G(d,p) and 6
      31++G(d,p) basis set have been used to determine ground state molecular
      geometries. The first order hyperpolarizability (beta0) and related properties
      (beta, alpha0 and Deltaalpha) of piracetam is calculated using B3LYP/6-31G(d,p)
      method on the finite-field approach. The stability of molecule has been analyzed
      by using NBO/NLMO analysis. The calculation of first hyperpolarizability shows
      that the molecule is an attractive molecule for future applications in non-linear
      optics. Molecular electrostatic potential (MEP) at a point in the space around a
      molecule gives an indication of the net electrostatic effect produced at that
      point by the total charge distribution of the molecule. The calculated HOMO and
      LUMO energies show that charge transfer occurs within these molecules. Mulliken
      population analysis on atomic charge is also calculated. Because of vibrational
      analysis, the thermodynamic properties of the title compound at different
      temperatures have been calculated. Finally, the UV-Vis spectra and electronic
      absorption properties are explained and illustrated from the frontier molecular
      orbitals. 

PMID- 24873891
TI  - Role of Cu2+ ions substitution in magnetic and conductivity behavior of nano
      CoFe2O4.
AB  - Cobalt copper ferrite nanopowders with composition Co1-xCuxFe2O4 (0.0<=x<=0.5)
      was synthesized by solution combustion method. The powder X-ray diffraction
      studies reveal the formation of single ferrite phase with particle size of ~11-35
      nm. Due to increase in electron density with in a material, X-ray density
      increase with increase of Cu2+ ions concentration. As Cu2+ ions concentration
      increases, saturation magnetization decreases from 38.5 to 26.7 emu g(-1).
      Further, the squareness ratio was found to be ~0.31-0.46 which was well below the
      typical value 1, which indicates the existence of single domain isolated
      ferrimagnetic samples. The dielectric and electrical modulus was studied over a
      frequency range of 1 Hz to 1 MHz at room temperature using the complex impedance
      spectroscopy technique. Impedance plots showed only one semi-circle which
      corresponds to the contributions of grain boundaries. The lower values of
      dielectric loss at higher frequency region may be quite useful for high frequency
      applications such as microwave devices.

PMID- 24873892
TI  - A detailed perceptive on the growth and characterization studies of para amino
      hippuric acid (PAHA) single crystals.
AB  - Single crystals of para amino hippuric acid (PAHA) were grown by slow evaporation
      technique. The spectral and its structural properties of the crystals were
      studied by FT-IR, micro-Raman and factor group analysis. The optical transparency
      in the UV-Visible regions was found to be good for non-linear optics (NLO)
      applications. Thermogravimetric analysis (TGA) and Differential Thermal Analysis
      (DTA) showed that the compound decomposes beyond 300 degrees C. The dielectric
      behavior of the compound predicts low dielectric loss at high frequency applied
      whereas in the case of mechanical behavior of the specimen hardness increases
      with increasing applied load. After certain weight increase, hardness gets
      saturated in the region of >=110. Relative second harmonic efficiency of the
      compound is found to be 1.8 times greater than that of potassium di-phosphate
      reference.

PMID- 24873893
TI  - Vibrational and quantum chemical investigation of cyclization of
      thiosemicarbazide group in 1-benzoyl-4-phenyl-3-thiosemicarbazide.
AB  - 1-Benzoyl-4-phenyl-3-thiosemicarbazide (H3bpt) was treated with acid - base in
      one sequence and base - acid in other sequence, both of which lead to ring
      formation of thiosemicarbazide group, giving N-phenyl-5-phenyl-1,3,4-thiadiazol-2
      amine (Hppta) in the first case and 4,5-diphenyl-2,4-dihydro-1,2,4-triazole-3
      thione (Hdptt) in the second case. The primary (H3bpt) as well as the resulting
      compounds (Hppta & Hdptt) has been characterized by elemental analyses, NMR, FTIR
      and Raman spectroscopic techniques. The quantum chemical calculations of the
      compounds are performed using DFT/B3LYP/6311G(d,p) method for geometry
      optimizations and also for prediction of the molecular properties. The
      cyclization is confirmed by disappearance of many bands belonging to the open
      chain subgroups of H3bpt such as; NH stretching, NH bending, CN stretching, NH
      puckering, CO stretching etc. The ring formation of 1-benzoyl-4-phenyl-3
      thiosemicarbazide (H3bpt) has been further confirmed by the appearance of many
      bands belonging to the closed ring of thiosemicarbazide in the resulting
      compounds Hppta and Hdptt. 

PMID- 24873895
TI  - Atmospheric deposition of mercury and methylmercury to landscapes and waterbodies
      of the Athabasca oil sands region.
AB  - Atmospheric deposition of metals originating from a variety of sources, including
      bitumen upgrading facilities and blowing dusts from landscape disturbances, is of
      concern in the Athabasca oil sands region of northern Alberta, Canada. Mercury
      (Hg) is of particular interest as methylmercury (MeHg), a neurotoxin which
      bioaccumulates through foodwebs, can reach levels in fish and wildlife that may
      pose health risks to human consumers. We used spring-time sampling of the
      accumulated snowpack at sites located varying distances from the major
      developments to estimate winter 2012 Hg loadings to a ~20 000 km(2) area of the
      Athabasca oil sands region. Total Hg (THg; all forms of Hg in a sample) loads
      were predominantly particulate-bound (79 +/- 12%) and increased with proximity to
      major developments, reaching up to 1000 ng m(-2). MeHg loads increased in a
      similar fashion, reaching up to 19 ng m(-2) and suggesting that oil sands
      developments are a direct source of MeHg to local landscapes and water bodies.
      Deposition maps, created by interpolation of measured Hg loads using
      geostatistical software, demonstrated that deposition resembled a bullseye
      pattern on the landscape, with areas of maximum THg and MeHg loadings located
      primarily between the Muskeg and Steepbank rivers. Snowpack concentrations of THg
      and MeHg were significantly correlated (r = 0.45-0.88, p < 0.01) with numerous
      parameters, including total suspended solids (TSS), metals known to be emitted in
      high quantities from the upgraders (vanadium, nickel, and zinc), and crustal
      elements (aluminum, iron, and lanthanum), which were also elevated in this
      region. Our results suggest that at snowmelt, a complex mixture of chemicals
      enters aquatic ecosystems that could impact biological communities of the oil
      sands region. 

PMID- 24873894
TI  - The beneficial effect of soybean (Glycine max (L.) Merr.) leaf extracts in adults
      with prediabetes: a randomized placebo controlled trial.
AB  - The present study investigated the effects of soybean leaf extracts (SLEs) on
      blood glucose, insulin resistance, body fat and dyslipidemia in prediabetes
      subjects, and compared them with the effects of banaba extracts (BE) which is
      known to ameliorate diabetes in several animals and clinical studies. Overweight
      subjects with mild hyperglycemia (fasting blood glucose level of 100-125 mg dL(
      1)) were randomly assigned to three groups and administered four capsules
      containing starch (2 g per day, Placebo), BE (300 mg per day, 0.3% corosolic
      acid) or SLE (2 g per day) during regular meals for 12 weeks. The SLE as well as
      BE significantly decreased the baseline-adjusted final blood glucose, HbA1c, HOMA
      IR and transaminase levels compared to the placebo group. The body weight, BMI
      and WHR were not different between the groups, but the baseline-adjusted final
      body fat content and waist circumference were lower in the BE and SLE groups than
      in the placebo group. Furthermore, the baseline-adjusted final plasma
      triglyceride concentration was lower in the BE and SLE groups compared to the
      placebo group. There were no significant differences in plasma total cholesterol
      and LDL-cholesterol concentrations between the groups. However, the SLE, but not
      the BE, significantly increased the plasma HDL-cholesterol concentration and the
      ratio of HDL-cholesterol to total cholesterol after 12 weeks of supplementation
      compared to the placebo group, while the atherogenic index was decreased. Taken
      together, these data suggest that SLE may play an important role in improving
      blood glucose, insulin resistance, adiposity, and dyslipidemia in prediabetes
      subjects consuming their habitual diet, similar to or better than BE. 

PMID- 24873896
TI  - Anal incontinence: long-term alterations in the incidence and healthcare usage.
AB  - OBJECTIVE: The aim of the study was to determine the alterations in the
      occurrence of incontinence and how subjects suffering from incontinence seek and
      receive healthcare services over a 10-year follow-up period. METHODS: Postal
      questionnaires (Wexner Incontinence Score, Fecal Incontinence Quality of Life
      Scale, a questionnaire to investigate the management of fecal incontinence and
      the frequency of urinary incontinence) were sent to subjects who had reported
      anal incontinence in our population-based study in 2003. For each incontinent
      person (n = 155) from the 2003 series, we identified two control subjects (n =
      310) who did not suffer from incontinence. RESULTS: Of the initially incontinent,
      47 (58%) had remained incontinent after a follow up of 10 years. Almost 80% of
      the incontinent subjects in 2012 were female. Of the 152 initially continent, 12
      (7.9%) had developed symptoms, all of whom were females. Urinary incontinence was
      present in approximately 60% of incontinent subjects. The majority (57.8%) of the
      subjects still incontinent in 2012 felt that they needed help for the complaint,
      but only 30.9% had received any, and only 7.4% received any benefit. The most
      common treatment was medication. The subjective incontinence impaired the quality
      of life. CONCLUSION: Incontinence is a chronic long-lasting disorder. The current
      management of anal incontinence is not satisfactory. The primary healthcare
      system should be more aware of the nature of this condition to find and offer
      treatment for the patients.

PMID- 24873897
TI  - Inner and outer annulus fibrosus cells exhibit differentiated phenotypes and
      yield changes in extracellular matrix protein composition in vitro on a
      polycarbonate urethane scaffold.
AB  - Since there is currently no optimal treatment for chronic neck or back pain that
      restores full spine functionality and disc height, recent research has focused on
      developing a regenerative medicine approach. This requires a better understanding
      of the phenotype nature of the different cell types present in disc tissues. In
      particular, there is very little known about the differentiated states of cells
      that co-exist within the annulus fibrosus (AF), despite the critical importance
      of this tissue in maintaining disc functionality. Maintenance of the
      differentiated states of these AF cells is imperative to the production of
      appropriate extracellular matrix (ECM) macromolecules and to the engineering of
      functional AF tissues. The objective of this study was to determine whether inner
      annulus fibrosus (IAF) cells when grown on polycarbonate urethane (PU) scaffolds
      in vitro will produce ECM molecules characteristic of IAF cells and different
      from outer annulus fibrosus (OAF) cells. OAF and IAF cells isolated from bovine
      coccygeal intervertebral disc were grown on nanofibrous PU for approximately 14
      days. The effect of culture time on ECM gene expression, DNA content, and the
      synthesis and retention of proteoglycans and collagens were evaluated for both
      OAF and IAF cells. The ECM accumulated was also characterized by immunostaining
      and Western blot. The tensile strengths of the tissue/scaffolds were evaluated at
      14 days. Both OAF and IAF cells both attached to PU and had similar DNA contents
      over time. IAF cells maintained relatively higher levels of COL2A1, ACAN and VCAN
      gene expression, and relatively lower levels of COL1A1 gene expression when
      compared with OAF cells, by 10 days of culture. IAF cells synthesized and
      retained similar amounts of total collagen and proteoglycans when compared with
      OAF cells. While both OAF and IAF cells accumulated type I collagen, only IAF
      cells accumulated type II collagen. Both cell types accumulated similar amounts
      of aggrecan but IAF cells accumulated higher amounts of versican as determined by
      immunostaining. In conclusion, nanofibrous PU scaffolds enabled the maintenance
      of most of the characteristic features of the IAF cell phenotype, and were
      different from those of OAF cells. 

PMID- 24873900
TI  - A mediation model to explain decision making under conditions of risk among
      adolescents: the role of fluid intelligence and probabilistic reasoning.
AB  - AIM: This study tested the mediating role of probabilistic reasoning ability in
      the relationship between fluid intelligence and advantageous decision making
      among adolescents in explicit situations of risk--that is, in contexts in which
      information on the choice options (gains, losses, and probabilities) were
      explicitly presented at the beginning of the task. METHOD: Participants were 282
      adolescents attending high school (77% males, mean age = 17.3 years). We first
      measured fluid intelligence and probabilistic reasoning ability. Then, to measure
      decision making under explicit conditions of risk, participants performed the
      Game of Dice Task, in which they have to decide among different alternatives that
      are explicitly linked to a specific amount of gain or loss and have obvious
      winning probabilities that are stable over time. RESULTS: Analyses showed a
      significant positive indirect effect of fluid intelligence on advantageous
      decision making through probabilistic reasoning ability that acted as a mediator.
      Specifically, fluid intelligence may enhance ability to reason in probabilistic
      terms, which in turn increases the likelihood of advantageous choices when
      adolescents are confronted with an explicit decisional context. CONCLUSIONS:
      Findings show that in experimental paradigm settings, adolescents are able to
      make advantageous decisions using cognitive abilities when faced with decisions
      under explicit risky conditions. This study suggests that interventions designed
      to promote probabilistic reasoning, for example by incrementing the mathematical
      prerequisites necessary to reason in probabilistic terms, may have a positive
      effect on adolescents' decision-making abilities.

PMID- 24873901
TI  - Developmental determinants of cardiac sensitivity to hypoxia.
AB  - Cardiac sensitivity to oxygen deprivation changes significantly during
      ontogenetic development. However, the mechanisms for the higher tolerance of the
      immature heart, possibilities of protection, and the potential impact of
      perinatal hypoxia on cardiac tolerance to oxygen deprivation in adults have not
      yet been satisfactorily clarified. The hypoxic tolerance of an isolated rat heart
      showed a triphasic pattern: significant decrease from postnatal day 1 to 7,
      followed by increase to the weaning period, and final decline to adulthood. We
      have observed significant ontogenetic changes in mitochondrial oxidative
      phosphorylation and mitochondrial membrane potential, as well as in the role of
      the mitochondrial permeability transition pores in myocardial injury. These
      results support the hypothesis that cardiac mitochondria are deeply involved in
      the regulation of cardiac tolerance to oxygen deprivation during ontogenetic
      development. Ischemic preconditioning failed to increase tolerance to oxygen
      deprivation in the highly tolerant hearts of newborn rats. Chronic hypoxic
      exposure during early development may cause in-utero or neonatal programming of
      several genes that can change the susceptibility of the adult heart to ischemia
      reperfusion injury; this effect is sex dependent. These results would have
      important clinical implications, since cardiac sensitivity in adult patients may
      be significantly affected by perinatal hypoxia in a sex-dependent manner. 

PMID- 24873898
TI  - Short communication: molecular epidemiology of HIV type 1 infection in
      Kazakhstan: CRF02_AG prevalence is increasing in the southeastern provinces.
AB  - To analyze HIV-1 genetic variants in Kazakhstan, HIV-1 sequences were obtained
      from 205 antiretroviral-treated (ART) and naive patients in 2009-2013. Samples
      were collected in the most populous cities and provinces of Kazakhstan. On the
      basis of phylogenetic analyses of partial pol sequences, subtype A variant
      intravenous drug user (IDU)-A (which is dominant in the former Soviet Union) was
      found in 60.0% of the individuals, followed by CRF02_AG (34.6%); the rest of the
      samples were subtype B, CRF03_AB, CRF63_02A1, and CRF07_BC. The proportion of
      CRF02_AG has increased significantly since 2001-2003, when it was less than 5%.
      The majority of the CRF02_AG cases were found in Almaty, the former capital and
      the most populous city in Kazakhstan. The IDU-A variant dominated in the
      industrial regions of northern and central Kazakhstan and some other regions.
      Both dominant HIV-1 genetic variants were almost equally represented in the two
      main transmission groups: IDUs and heterosexuals. The analysis of drug-resistant
      mutations found a low prevalence of drug resistance in 165 therapy-naive
      individuals (3.0%). Thus, in the beginning of the second decade of the 2000s, the
      HIV epidemic in Kazakhstan is driven by two main genetic variants: IDU-A and
      CRF02_AG.

PMID- 24873903
TI  - Magnetic control of electrochemical processes at electrode surface using iron
      rich graphene materials with dual functionality.
AB  - Metal-doped graphene hybrid materials demonstrate promising capabilities in
      catalysis and various sensing applications. There also exists great interest for
      on-demand control of the selectivity of many electrochemical processes. In this
      work, an iron-doped thermally reduced graphene oxide (Fe-TRGO) was prepared and
      used to investigate the possibility of a reproducible, magnetically controlled
      method to modulate electrochemical reactivities through a scalable method. We
      made use of the presence of both magnetic and electrocatalytic properties in the
      Fe-TRGOs to induce attraction and removal of the Fe-TRGO material onto and off
      the working electrode surfaces magnetically, thereby controlling the
      electrochemical oxidation and reduction processes. The outstanding
      electrochemical performance of the Fe-TRGO material was evident, with enhanced
      current signals and lower peak potentials observed upon magnetic activation.
      Reversible and reproducible cycles of activation and deactivation were obtained
      as the peak heights and peak potentials remained relatively consistent with no
      apparent carryover between every step. Both components of Fe-TRGO play an
      electrocatalytic role in the electrochemical sensing. In the cases of the oxygen
      reduction reaction and reduction of cumene hydroperoxide, the iron oxide plays
      the role of an electrocatalyst, while in the cases of ascorbic acid, the enhanced
      electroactivity originates from the high surface area of the graphene portion in
      the Fe-TRGO hybrid material. The feasibility of this magnetically switchable
      method for on-demand sensing and energy production thus brings about potential
      developments for future electrochemical applications. 

PMID- 24873904
TI  - The self-disproportionation of the enantiomers (SDE) of methyl n-pentyl sulfoxide
      via achiral, gravity-driven column chromatography: a case study.
AB  - This work explores the self-disproportionation of enantiomers (SDE) of chiral
      sulfoxides via achiral, gravity-driven column chromatography using methyl n
      pentyl sulfoxide as a case study. A major finding of this work is the remarkable
      persistence and high magnitude of the SDE for the analyte. Thus, it is the first
      case where SDE is observed even in the presence of MeOH in the mobile phase. The
      study demonstrated the practical preparation, in line with theory, of
      enantiomerically pure (>99.9% ee) samples of methyl n-pentyl sulfoxide starting
      from a sample of only modest ee (<35%). Remarkably, it was found that the order
      of elution was inverted, i.e. enantiomerically depleted fractions preceded later
      eluting enantiomerically enriched ones, when the stationary phase was changed
      from silica gel to aluminum oxide. To the best of our knowledge, this is the
      first occurrence of inverted SDE behavior due solely to a change in the
      stationary phase. Aberrant SDE behavior was observed in that the ee did not
      always fall continuously during the progression of the chromatography, and this
      was attributed to the complexity of the system at hand which cannot be described
      in simple terms such as the formation only of homo- and heterochiral dimers based
      on a single interaction. The results nevertheless suggest that all compounds with
      a chiral sulfoxide moiety in their structure are likely to exhibit the SDE
      phenomenon and thus this work constitutes the first example of SDE
      predictability. Moreover, it could well be that optical purification based on the
      SDE phenomenon is a simple, convenient, and inexpensive method for the optical
      purification of this class of compounds with a high degree of proficiency. 

PMID- 24873902
TI  - Tamoxifen reduces infiltration of inflammatory cells, apoptosis and inhibits
      IKK/NF-kB pathway after spinal cord injury in rats.
AB  - In this study, neuroprotective effect of tamoxifen has been explored in spinal
      cord injury (SCI) in rats by examining factors influencing IKK/NF-kB pathway in
      SCI in rats. It has been shown in several studies that IKK/NF-kB signaling
      pathway plays a key role in pathophysiology of SCI. In this study, three groups
      of rats (n = 17 each) were selected that included, tamoxifen group (here
      tamoxifen was injected after SCI in rats), SCI group (here only dimethylsulfoxide
      was administered after inducing SCI in rats) and sham group (here only
      laminectomy was performed). The effect of tamoxifen (5 mg/kg) on various factors
      responsible for activation of IKK/NF-kB signaling pathway including NF-kB p65,
      phosphorylated I-kBalpha was studied through Western blotting as well as
      densitometry. The examination of expression of active caspase-3 and
      myeloperoxidase activity was also carried out through Western blot analysis and
      densitometry. A comparison of three groups of rats showed that administration of
      tamoxifen significantly reduced the expression of NF-kB p65 and phosphorylated I
      kBalpha (P < 0.05) compared to control. It also attenuated the expression of
      active caspase-3 resulting in the reduction of apoptosis, and infiltration of
      leukocytes to the injury site was also greatly reduced in the group where
      tamoxifen was administered. Statistical analysis through SPSS 13.0 software
      showed a significant decrease in the expression of inflammatory factors in groups
      where tamoxifen was administered. We conclude that tamoxifen possesses the
      potential neuroprotective effects that can be explored further for future
      therapeutic techniques in treating spinal cord injuries.

PMID- 24873906
TI  - Effect of population density on reproduction in Microtus fortis under laboratory
      conditions.
AB  - Between December 2011 and March 2012, the reproductive characteristics of
      Microtus fortis reared in the laboratory at different population densities were
      assessed. In all, 258 male and female voles were randomly divided into 4 groups
      and reared at densities of 2, 4, 6, and 8 animals per cage (sex ratio: 1:1). The
      results showed that the pregnancy rate (chi2 = 21.671, df = 3, P < 0.001) and
      first farrowing interval (F = 12.355, df = 3, P < 0.001) were significantly
      different among the different population density groups, but the mean litter size
      (mean +/- SD) was not (F = 2.669, df = 3, P > 0.05). In particular, the
      reproductive index and sex hormone levels showed a significant difference among
      the different density groups studied. 

PMID- 24873905
TI  - Abnormal functional activation and maturation of fronto-striato-temporal and
      cerebellar regions during sustained attention in autism spectrum disorder.
AB  - OBJECTIVE: Sustained attention problems are common in people with autism spectrum
      disorder (ASD) and may have significant implications for the diagnosis and
      management of ASD and associated comorbidities. Furthermore, ASD has been
      associated with atypical structural brain development. The authors used
      functional MRI to investigate the functional brain maturation of attention
      between childhood and adulthood in people with ASD. METHOD: Using a
      parametrically modulated sustained attention/vigilance task, the authors examined
      brain activation and its linear correlation with age between childhood and
      adulthood in 46 healthy male adolescents and adults (ages 11-35 years) with ASD
      and 44 age- and IQ-matched typically developing comparison subjects. RESULTS:
      Relative to the comparison group, the ASD group had significantly poorer task
      performance and significantly lower activation in inferior prefrontal cortical,
      medial prefrontal cortical, striato-thalamic, and lateral cerebellar regions. A
      conjunction analysis of this analysis with group differences in brain-age
      correlations showed that the comparison group, but not the ASD group, had
      significantly progressively increased activation with age in these regions
      between childhood and adulthood, suggesting abnormal functional brain maturation
      in ASD. Several regions that showed both abnormal activation and functional
      maturation were associated with poorer task performance and clinical measures of
      ASD and inattention. CONCLUSIONS: The results provide first evidence that
      abnormalities in sustained attention networks in individuals with ASD are
      associated with underlying abnormalities in the functional brain maturation of
      these networks between late childhood and adulthood.

PMID- 24873907
TI  - PCR-based identification of adriatic specimen of three scorpionfish species
      (Scorpaenidae, Teleostei).
AB  - The identification of three scorpionfish species, the black scorpionfish
      (Scorpaena porcus Linnaeus, 1758), the large-scaled scorpionfish (S. scrofa
      Linnaeus, 1758) and the small red scorpionfish (S. notata Rafinesque, 1810) is
      possible in adults by morphometry, but often problematic in juveniles due to
      their similar phenotypes. To develop a molecular species identification tool,
      first, we have analyzed the genetic similarity of the three species by a PCR
      based 'blind method' that amplified bands from various locations of the genome.
      We found high levels of nucleotide similarity between S. porcus and S. scrofa,
      whereas S. notata showed a higher level of divergence from the other two species.
      Then, we have searched these patterns for differences between the genomes of
      Adriatic specimen of these three species and identified several species-specific
      products in two of them. For the third one a species-specific primer pair
      amplifying from the 16S ribosomal DNA was designed. One marker for each species
      was cloned, sequenced and converted into Sequence Characterized Amplified Region
      (SCAR) markers amplified by specific primer pairs. The SCAR markers amplified
      robust bands of limited variability from the target species, while no or only
      occasional weak products were obtained from the other two, proving that they can
      be used for molecular identification of these three species. These markers can
      help the conservation and future analysis of these three species as well as their
      possible selection programs for aquaculture purposes. 

PMID- 24873908
TI  - Polyphenol composition and antioxidant capacity from different extracts of Aster
      scaber.
AB  - Phenolic contents and antioxidant capacities from different solvent extracts
      (petroleum ether, ethyl acetate, methanol, butanol and water) of Aster scaber
      leaf were investigated. Antioxidant activity was evaluated by three different
      methods, namely DPPH radical scavenging activity, reducing power assay and
      phosphomolybdenum activity. A total of twenty-three polyphenolic compounds were
      identified and quantified from A. scaber leaf extracts, including hydroxybenzoic
      acids, hydroxycinnamic acids, flavonols and other groups of phenolic compounds.
      Ultra high performance liquid chromatography (UHPLC) analysis of the leaf extract
      revealed that myricetin (4850.45 MUg/g) was the most dominant flavonols, compared
      to quercetin and kaempferol. Caffeic acid was the dominant phenolic compound in
      A. scaber leaf extracts, it constituted about 104.20 MUg/g, followed by gentisic
      acid (84.50 MUg/g), gallic acid (61.05 MUg/g) and homogentisic acid (55.65
      MUg/g). The total phenolic and flavonoid content was the highest in ethyl acetate
      extract (322.43 and 6.51 mg/g). The decreasing order of antioxidant activity
      among the A. scaber leaf extracts assayed through all the three methods was found
      to be ethyl acetate > butanol > methanol > petroleum ether > water extract. 

PMID- 24873909
TI  - A preliminary report on the genetic variation in pointed gourd (Trichosanthes
      dioica Roxb.) as assessed by random amplified polymorphic DNA.
AB  - Pointed gourd (Trichosanthes dioica Roxb.) is an economically important cucurbit
      and is extensively propagated through vegetative means, viz vine and root
      cuttings. As the accessions are poorly characterized it is important at the
      beginning of a breeding programme to discriminate among available genotypes to
      establish the level of genetic diversity. The genetic diversity of 10 pointed
      gourd races, referred to as accessions was evaluated. DNA profiling was generated
      using 10 sequence independent RAPD markers. A total of 58 scorable loci were
      observed out of which 18 (31.03%) loci were considered polymorphic. Genetic
      diversity parameters [average and effective number of alleles, Shannon's index,
      percent polymorphism, Nei's gene diversity, polymorphic information content
      (PIC)] for RAPD along with UPGMA clustering based on Jaccard's coefficient were
      estimated. The UPGMA dendogram constructed based on RAPD analysis in 10 pointed
      gourd accessions were found to be grouped in a single cluster and may represent
      members of one heterotic group. RAPD analysis showed promise as an effective tool
      in estimating genetic polymorphism in different accessions of pointed gourd. 

PMID- 24873910
TI  - Growth regulator requirement for in vitro embryogenic cultures of snowdrop
      (Galanthus nivalis L.) suitable for germplasm preservation.
AB  - In this study, we report on the production of bulb scale-derived tissue cultures
      capable of efficient shoot and plant regeneration in three genotypes of snowdrop
      (Galanthus nivalis L., Amaryllidaceae), a protected ornamental plant. For culture
      line A, high auxin and low cytokinin concentration is required for callus
      production and plant regeneration. The type of auxin is of key importance: alpha
      naphthaleneacetic acid (NAA) in combination with indole-3-acetic acid (IAA) at
      concentrations of 2 mg L-1 or 2-10 mg L-1 NAA with 1 mg L-1 N6-benzyladenine
      (BA), a cytokinin on full-strength media are required for regeneration. Cultures
      showing regeneration were embryogenic. When lines B and C were induced and
      maintained with 2 mg L-1 NAA and 1 mg L-1 BA, they produced mature bulblets with
      shoots, without roots. Line A produced immature bulblets with shoots under the
      above culture condition. Amplified Fragment Length Polymorphism (AFLP) analysis
      showed that (i) genetic differences between line A and its bulb explants were not
      significant, therefore these tissue cultures are suitable for germplasm
      preservation, and (ii) different morphogenetic responses of lines A, B and C
      originated from genetic differences. Culture line A is suitable for field
      growing, cultivation and germplasm preservation of G. nivalis and for the
      production of Amaryllidaceae alkaloids. 

PMID- 24873911
TI  - Effect of polyethylene glycol induced drought stress on photosynthesis in two
      chickpea genotypes with different drought tolerance.
AB  - Responses of parameters related with photosynthesis and the involvement of
      various factors in photosynthetic damage in two chickpea genotypes, Gokce
      (tolerant) and Kusmen (sensitive) under drought stress were assessed.
      Photosynthetic pigment content decreased under drought stress in two genotypes.
      Significant decreases in gs, Pn and E were determined in Kusmen. No significant
      change in these parameters was measured in Gokce under drought stress. Fv/Fm,
      PhiPS2 and ETR decreased in drought stressed plants of Kusmen as compared to
      control plants however Fv/Fm, PhiPS2 and ETR did not change in Gokce under
      drought stress. Increases in NPQ were determined under stress in both genotypes.
      Drought stress did not affect rubisco activity and rubisco concentration in Gokce
      while, the activity and the content declined in Kusmen. The drought tolerance of
      the Gokce genotype is a consequence of a balance among leaf water potential,
      stomatal conductance, photosynthesis, and transpiration. On the other hand,
      photosynthesis in Kusmen may be not only restricted by stomatal limitations but
      also by non-stomatal limitations under drought stress. 

PMID- 24873912
TI  - Biomass derived from transgenic tobacco expressing the Arabidopsis CESA3ixr1-2
      gene exhibits improved saccharification.
AB  - Studies in Arabidopsis thaliana and Nicotiana tabacum L. variety Samsun NN
      demonstrated that expression of the CESA3 cellulose synthase gene that contains a
      point mutation, named ixr1-2, results in greater conversion of plant-derived
      cellulose to fermentable sugars. The present study was designed to examine the
      improved enzymatic saccharification efficiency of lignocellulosic biomass of
      tobacco plants expressing AtCESA3ixr1-2. Three-month-old AtCESA3ixr1-2 transgenic
      and wild-type tobacco plants (Nicotiana tabacum L. variety Samsun NN) were grown
      in the presence and absence of isoxaben. Biomass obtained from leaf, stem, and
      root tissues were analyzed for enzymatic saccharification rates. During enzymatic
      saccharification, 45% and 25% more sugar was released from transgenic leaf and
      stem samples, respectively, when compared to the wild-type samples. This gain in
      saccharification efficiency was achieved without chemical or heat pretreatment.
      Additionally, leaf and stem biomass from transgenic AtCESA3ixr1-2 requires a
      reduced amount of enzyme for saccharification compared to biomass from wild-type
      plants. From a practical standpoint, a similar strategy could be employed to
      introduce the mutated CESA into energy crops like poplar and switchgrass to
      improve the efficiency of biomass conversion. 

PMID- 24873913
TI  - Routine sample preparation and HPLC analysis for ascorbic acid (vitamin C)
      determination in wheat plants and Arabidopsis leaf tissues.
AB  - Plants have developed various mechanisms to protect themselves against oxidative
      stress. One of the most important non-enzymatic antioxidants is ascorbic acid.
      There is thus a need for a rapid, sensitive method for the analysis of the
      reduced and oxidised forms of ascorbic acid in crop plants. In this paper a
      simple, economic, selective, precise and stable HPLC method is presented for the
      detection of ascorbate in plant tissue. The sensitivity, the short retention time
      and the simple isocratic elution mean that the method is suitable for the routine
      quantification of ascorbate in a high daily sample number. The method has been
      found to be better than previously reported methods, because of the use of an
      economical, readily available mobile phase, UV detection and the lack of
      complicated extraction procedures. The method has been tested on Arabidopsis
      plants with different ascorbate levels and on wheat plants during Cd stress. 

PMID- 24873914
TI  - Regulation of the unbalanced redox state in a Schizosaccharomyces pombe tert
      butyl hydroperoxide-resistant mutant.
AB  - The one-gene mutation in the tert-butyl hydroperoxide-resistant mutant hyd1-190
      of the fission yeast Schizosaccharomyces pombe led to a 4-fold increase in
      resistance to t-BuOOH and decreased specific concentrations of superoxide and
      total thiols in comparison with the parental strain hyd+. It suggested an
      unbalanced redox state of the cells, which induced continuously increased
      specific activities of glutathione peroxidase, glutathione reductase and
      glutathione S-transferase and decreased activities of the antioxidant enzymes
      superoxide dismutases and glucose-6-phosphate dehydrogenase to regulate the redox
      balance of the mutation-induced permanent, low-level but tolerable internal
      stress. These results may contribute to the understanding of internal, oxidative
      stress-related human diseases. 

PMID- 24873915
TI  - Variability of microcystins and its synthetase gene cluster in Microcystis and
      Planktothrix waterblooms in shallow lakes of Hungary.
AB  - Waterbloom samples of Microcystis aeruginosa and Planktothrix agardhii were
      collected from a variety of ponds, lakes and reservoirs in Hungary. Samples were
      tested with matrix-assisted laser desorption/ionization - time-of-flight mass
      spectrometry (MALDI-TOF MS) to identify the microcystin forms. The concentration
      of the microcystins was measured with capillary electrophoresis and the toxicity
      was tested by sinapis test. DNA was extracted from the samples and tested using a
      range of primers linked to the biosynthesis of microcystin. All of the fourteen
      collected samples gave positive results for the presence of the mcy genes with
      PCR products with sizes between of 425 and 955 bp, respectively, indicating the
      presence of the genes implicated in the production of microcystins. The results
      showed that a wide range of microcystin (MC) forms were detected in the
      Microcystis containing samples, among which MC-LR, -RR, and -YR were the most
      common. The highest MC concentration was 15,701 mg g-1, which was detected in an
      angling pond. The samples containing Planktothrix agardhii were less toxic, and
      the most common form in this species was the Asp3-MC-LR. 

PMID- 24873916
TI  - Strategies for multivessel revascularization in patients with diabetes: the
      FREEDOM trial.

PMID- 24873917
TI  - Record pure zincblende phase in GaAs nanowires down to 5 nm in radius.
AB  - We report the Au catalyst-assisted synthesis of 20 MUm long GaAs nanowires by the
      vapor-liquid-solid hydride vapor phase epitaxy (HVPE) exhibiting a polytypism
      free zincblende phase for record radii lower than 15 nm down to 5 nm. HVPE makes
      use of GaCl gaseous growth precursors at high mass input of which fast
      dechlorination at the usual process temperature of 715  degrees C results in high
      planar growth rate (standard 30-40 MUm/h). When it comes to the vapor-liquid
      solid growth of nanowires, fast solidification at a rate higher than 100 MUm/h is
      observed. Nanowire growth by HVPE only proceeds by introduction of precursors in
      the catalyst droplets from the vapor phase. This promotes almost pure axial
      growth leading to nanowires with a constant cylinder shape over unusual length.
      The question of the cubic zincblende structure observed in HVPE-grown GaAs
      nanowires regardless of their radius is at the heart of the paper. We demonstrate
      that the vapor-liquid-solid growth in our conditions takes place at high liquid
      chemical potential that originates from very high influxes of both As and Ga.
      This yields a Ga concentration systematically higher than 0.62 in the Au-Ga-As
      droplets. The high Ga concentration decreases the surface energy of the droplets,
      which disables nucleation at the triple phase line thus preventing the formation
      of wurtzite structure whatever the nanowire radius is.

PMID- 24873918
TI  - The chimney technique with the Ovation abdominal stent graft system: an ideal
      platform for self-expandable renal stents?

PMID- 24873919
TI  - Predisposing factors of liver necrosis after transcatheter arterial
      chemoembolization in liver metastases from neuroendocrine tumor.
AB  - PURPOSE: To investigate predictive factors for liver necrosis after transcatheter
      arterial chemoembolization (TACE) of neuroendocrine liver metastases. METHODS: A
      total of 164 patients receiving 374 TACE were reviewed retrospectively to analyze
      predictive factors of liver necrosis. We analyzed patient age and sex; metastasis
      number and location; percentage of liver involvement; baseline liver function
      test; and pretreatment imaging abnormalities such as bile duct dilatation (BDD),
      portal vein narrowing (PVN), and portal vein thrombosis (PVT). We analyzed TACE
      technique such as Lipiodol or drug-eluting beads (DEB) as the drug's vector; dose
      of chemotherapy; diameter of DEB; and number, frequency, and selectivity of TACE.
      RESULTS: Liver necrosis developed after 23 (6.1 %) of 374 TACE. In multivariate
      analysis, DEB > 300 MUm in size induced more liver necrosis compared to Lipiodol
      (odds ratio [OR] 35.20; p < 0.0001) or with DEB < 300 MUm in size (OR 19.95; p <
      0.010). Pretreatment BDD (OR 119.64; p < 0.0001) and PVT (OR 9.83; p = 0.030)
      were predictive of liver necrosis. BDD or PVT responsible for liver necrosis were
      present before TACE in 59 % (13 of 22) and were induced by a previous TACE in 41
      % (9 of 22) of cases. CONCLUSION: DEB > 300 MUm in size, BDD, and PVT are
      responsible for increased rate of liver necrosis after TACE. Careful analysis of
      BDD or PVT on pretreatment images as well as images taken between two courses can
      help avoid TACE complications.

PMID- 24873920
TI  - Diagnostic accuracy of MRI-guided percutaneous transthoracic needle biopsy of
      solitary pulmonary nodules.
AB  - OBJECTIVE: The purpose of our study was to evaluate the diagnostic accuracy of
      MRI-guided percutaneous transthoracic needle biopsy (PTNB) of solitary pulmonary
      nodules (SPNs). METHODS: Retrospective review of 69 patients who underwent MR
      guided PTNB of SPNs was performed. Each case was reviewed for complications. The
      final diagnosis was established by surgical pathology of the nodule or clinical
      and imaging follow-up. Pneumothorax rate and diagnostic accuracy were compared
      between two groups according to nodule diameter (<=2 vs. >2 cm) using chi (2)
      chest and Fisher's exact test, respectively. RESULTS: The success rate of single
      puncture was 95.6 %. Twelve (17.4 %) patients had pneumothorax, with 1 (1.4 %)
      requiring chest tube insertion. Mild hemoptysis occurred in 7 (7.2 %) patients.
      All of the sample material was sufficient for histological diagnostic evaluation.
      Pathological analysis of biopsy specimens showed 46 malignant, 22 benign, and 1
      nondiagnostic nodule. The final diagnoses were 49 malignant nodules and 20 benign
      nodules basing on postoperative histopathology and clinical follow-up data. One
      nondiagnostic sample was excluded from calculating diagnostic performance. A
      sensitivity, specificity, accuracy, positive predictive value, and negative
      predictive value in diagnosing SPNs were 95.8, 100, 97.0, 100, and 90.9 %,
      respectively. Pneumothorax rate, diagnostic sensitivity, and accuracy were not
      significantly different between the two groups (P > 0.05). CONCLUSIONS: MRI
      guided PTNB is safe, feasible, and high accurate diagnostic technique for
      pathologic diagnosis of pulmonary nodules.

PMID- 24873921
TI  - Surveillance after endovascular abdominal aortic aneurysm repair.
AB  - Surveillance after endovascular abdominal aortic aneurysm repair (EVAR) is widely
      considered mandatory. The purpose of surveillance is to detect asymptomatic
      complications, so that early secondary intervention can prevent late aneurysm
      rupture. CT angiography has been taken as the reference standard imaging test,
      but there is increasing interest in using other modalities to reduce the use of
      ionising radiation and iodinated contrast. As a result, there is wide
      heterogeneity in surveillance strategies used among EVAR centres. We reviewed the
      current evidence available on the outcomes of different imaging modalities and
      surveillance strategies following EVAR. 

PMID- 24873922
TI  - Re-defining Parkinson's disease.
AB  - Analyzing non-motor symptoms in Parkinson's disease (PD) leads to critically re
      define and update the disorder itself. The present Editorial encompasses
      epidemiological and clinical studies on PD patients joined with experimental
      findings to provide a novel definition of PD based on clinical, neuroanatomical
      and neurobiological findings.In fact, the plethora of symptoms described in PD
      patients are due to specific anatomical alterations which cluster in specific
      disease phenotypes. These PDs differ for disease onset and progression, disease
      severity and specific cluster of non-motor disturbances. Despite the variety of
      PD phenotypes, it is now well established that in almost all PD subgroups (except
      those autosomic recessive selective disorders exemplified by Parkin disease) a
      core anatomical defniition exists recruiting a variety of brainstem monoamine
      nuclei. Such a variety of PD pathologies can be defined as monoamine brainstem
      disorder (MBD). 

PMID- 24873923
TI  - Methodological Issues on the epidemiology of non motor symptoms in Parkinson's
      disease.
AB  - The increasing interest in non-motor symptoms in Parkinson's disease due to the
      widening knowledge in the neurobiological field, brought to considering PD as a
      complex disease. This requires a proper characterization of the natural history
      of the disease using the appropriate epidemiological tools, along with the
      implementation in clinical practice of a standard a multi-professional approach.
      Available evidence on the frequency of non-motor symptoms in PD is reported in
      studies with very heterogeneous designs and diagnostic measures, and using a
      great variety of epidemiological estimates. In particular, there are no studies
      reporting the frequency of non-motor symptoms in a cohort of incident PD patients
      using point prevalence, incidence rate, and cumulative incidence. A mini-review
      of cross-sectional and longitudinal studies on three non-motor
      symptoms/conditions (dementia, depression, ICDs) in patients with PD confirms
      these premises and highlights the need of higher quality studies, both from a
      methodological and a clinical point of view. 

PMID- 24873924
TI  - A clinical overview of non-motor symptoms in Parkinson's Disease.
AB  - Although Parkinson's disease (PD) is diagnosed on the basis of motor symptoms,
      including slowness of movement, tremor, rigidity and difficulties with balance
      and walking, now we are aware that non-motor symptoms are highly prevalent, since
      they can anticipate motor symptoms and can cause severe consequences. Several
      studies have shown that non-motor symptoms, such as depression, anxiety and
      apathy, psychosis (e.g., hallucinations, delusions), sleep disturbance, and pain
      may have a greater adverse impact on quality of life and health economics
      compared with motor symptoms. Non-motor symptoms can be divided into four
      domains: neuropsychiatric (e.g., depression, anxiety, apathy, hallucinations,
      dementia), autonomic (e.g., constipation, orthostatic hypotension, urinary
      changes, sweating abnormalities), sleep (e.g., insomnia, sleep fragmentation,
      excessive daytime sleepiness, rapid eye movement, sleep behavioural disorder,
      restless leg syndrome), and sensory dysfunction (e.g., pain, olfactory
      dysfunction). This review addresses diagnosis and treatment of these disorders.
      The causative mechanisms remain complex, since they reflect the widespread
      brainstem and cortical pathology of PD, with involvement of several
      neurotransmitters, including dopamine (DA), serotonin, norepinephrine, and
      acetylcholine. The diagnosis is often challenging, especially for psychiatric
      disorders, and in particular affective disorders, because somatic features of
      psychopathology may overlap with the movement disorder itself. Treatments used
      are limited and psychiatric drugs may not be as effective as in general
      population. Evidence based medicine is quite poor and it still requires well
      designed clinical studies. 

PMID- 24873925
TI  - Heterogeneous pathologies associated with dementia in Parkinsonism share a prion
      like spreading mechanism.
AB  - Cognitive alterations accompany or follow motor disorders in subjects with
      Parkinsonism. The canonical phenotypeof the Parkinson's disease Dementia (PD-D)
      or Lewy Body Dementia (LBD) includes deficit of attention, executiveand
      visuospatial functions, and presents often with apathy, hallucinations,
      delusions, excessive daytime sleepiness,or sleep disorders. However, the clinical
      expression may overlap with other neurodegenerative diseases associatedwith
      cognitive disorders. Thus, while clinicians rely on phenomenological patterns to
      infer the disease causing thecognitive impairment, the inference is weakened by
      the heterogeneous clinical expression of the disease. In addition,recent post
      mortem studies seem to undermine the supposed pathology-phenotype coherence,
      making it moreand more unreliable the diagnosis based on symptoms. The lack of
      coherence between phenotype and pathologymay support the speculation about a
      common mechanism underlying the progression of the disease. While it is
      verylikely that a distinct, specific causal event determines the disease itself,
      the progression might well follow commonpatterns. A number of observations
      suggest that progressive diseases, which cause cognitive impairment, share aprion
      like mechanism. A seeding process is supposed to account for the spreading of the
      lesion. 

PMID- 24873926
TI  - Neurobiology and neuroanatomy of psychiatric symptoms in parkinsonism.
AB  - The present article aims to review state-of-the-art evidence of altered
      neurobiology and neuroanatomy underlyingpsychiatric symptoms in parkinsonism.
      This issue covers a wide range of symptoms encompassing anxiety, mooddisorders,
      psychosis as well as substance abuse and specific compulsive behaviors. Such a
      complex nosographymakes it impossible to deal with the neurobiology and
      neuroanatomy of each psychopathological condition perse, unless offering a
      trivial list of symptoms joined with brief explanations reporting potential
      causal mechanisms.This approach would only provide a rough synthesis of what
      previously reported without adding neither novelconcepts nor evidence to improve
      our insight into the neurobiology of parkinsonism as a psychiatric
      condition.Therefore, the analytical description of each psychiatric symptom
      associated with parkinsonism will be avoided butit will be referenced instead. In
      contrast, the present article will focus on the mechanisms why such a class of
      nonmotorsymptoms clusters in parkinsonian patients. In addition, we will seek to
      establish the relationship betweenthe occurrence of a given psychiatric condition
      and specific parkinsonian phenotypes. Again, an emphasis will begiven to the
      occurrence of behavioral fluctuations in parkinsonism where both motor and
      psychiatric symptomsmay possess a specific timing. The timing of these
      fluctuations will be related to the timing of dopamine substitutiontherapy and
      involvement of multiple neurotransmitters and brain regions as well. We provide
      evidence showingthat specific parkinsonian phenotypes (and genotypes) possess a
      widespread neuropathology, which in turn associatesto a fairly specific
      psychopathology. In contrast, other phenotypes (and genotypes) bring to very
      selectiveneuronal degeneration where the occurrence of psychiatric symptoms is
      rare if not absent at all. These clinicalpathological phenotypes associate with
      specific molecular mechanisms in the dynamics of neurobiology of disease. 

PMID- 24873927
TI  - Novel aspects of striatal plasticity associated with long-term levo-dopa
      administration.
AB  - "Striatal plasticity" is a term describing a variety of morphological and
      functional changes occurring both at pre- and post-synaptic level within the
      basal ganglia. In most cases striatal plasticity occurs when a loss of dopamine
      (DA) fibers in the striatum, in the course of Parkinsonism takes place. Plastic
      events include early pre-synaptic and long-term post-synaptic changes. In the
      context of long-term changes associated with striatal plasticity the role of
      intrinsic striatal catecholamine cells is emerging. This neuronal population
      expresses both tyrosine hydroxylase (TH) and DA transporter (DAT). These TH
      positive cells are normally resident within the human caudate putamen but they
      dramatically increase during parkinsonism reaching an amount roughly
      corresponding to 50% of nigrostriatal neurons counted in control brains. This
      evidence led to hypothesize fascinating mechanisms bridging these neurons either
      with compensatory changes or the onset of aberrant behavioral activity. Very
      recently  the occurrence of these neurons was described during DA replacement
      therapy in parkinsonism, thus suggesting that these cells may represent the
      anatomical basis for plastic phenomena.  Thus, the present article, in the
      attempt to describe novel mechanisms generating striatal plasticity, details
      these cells in development and adult life and their potential role in maturation
      phenomena occurring in parkinsonism. 

PMID- 24873929
TI  - The neurobiology of the spinal cord in experimental parkinsonism and Parkinson's
      disease.
AB  - The neurobiology of non-motor symptoms in Parkinson's disease (PD) reveals a
      number of unexpected areas which once were not recognized a priori as part of the
      neuropathology underlying PD. These areas may belong either to central nervous
      system or periphery. Among central areas major efforts in the last decade led to
      recognize a number of brain nuclei as part of the disease spreading or disease
      onset in PD patients. Unexpectedly recent evidence deriving from pathological
      studies in PD patients and corroborated by experimental models of PD provided
      clear evidence that the spinal cord is often recruited in PD pathology. Such an
      involvement is intriguing since the major degenerative disease of the spinal cord
      (amyotrophic lateral sclerosis) features the involvement of dopaminergic neurons
      of the substantia nigra pars compacta, while some environmental (parkinsonism,
      ALS, and dementia of Guam) and genetic (Kufor-Rakeb syndrome) diseases are known
      to be characterized by mixed degeneration of pyramidal and extrapyramidal
      regions. Thus, the clear-cut between degeneration of dopaminergic neurons in the
      substantia nigra and the loss of pyramidal motor system appears now more as a
      continuum of   degeneration which converge in abnormal activity and cell
      pathology of motor neurons as a final common pathway. Among motor neurons,
      visceral efferent cells of the spinal cord are involved and provide a robust
      neurobiological findings which may justify a variety of non-motor autonomic
      symptoms which characterize PD. Neurodegeneration in the spinal cord extends to
      the dorsal horn of the grey matter posing an intriguing link between PD and
      sensory alterations. The present manuscript reviews the involvement of multiple
      regions of the spinal cord in PD and experimental parkinsonism in the attempt to
      provide both a neurobiological background to understand non motor symptoms and to
      provide the anatomical basis for disease spreading. 

PMID- 24873928
TI  - The neurobiology of dysautonomia in Parkinson's disease.
AB  - Neurodegenerative diseases (NDs) include a large variety of disorders that
      affects specific areas of the centralnervous system, leading to psychiatric and
      movement pathologies. A common feature that characterizes thesedisorders is the
      neuronal formation and accumulation of misfolded protein aggregates that lead to
      cell death. Inparticular, different proteinaceous aggregates accumulate to
      trigger a variety of clinical manifestations: prionprotein (PrPSc) in prion
      diseases, beta-amyloid (Abeta) in Alzheimer's disease (AD), alpha-synuclein in
      Parkinson's disease(PD), huntingtin in Huntington's disease (HD), superoxide
      dismutase and TDP-43 in amyotrophic lateral sclerosis(ALS), tau in tauopathies.
      Non-motor alterations also occur in several viscera, in particular the
      gastrointestinaltract. These often precede the onset of motor symptoms by several
      years. For this reason, dysautonomic changescan be predictive of NDs and their
      correct recognition is being assuming a remarkable importance. This
      peculiarfeature led more and more to the concept that neurodegeneration may
      initiate in the periphery and propagate retrogradelytowards the central nervous
      system in a prion-like manner. In recent years, a particular attention
      wasdedicated to the clinical assessment of autonomic disorders in patients
      affected by NDs. In this respect, experimentalanimal models have been developed
      to understand the neurobiology underlying these effects as well as toinvestigate
      autonomic changes in peripheral organs. This review summarizes experimental
      studies that have beencarried out to understand autonomic symptoms in NDs, with
      the purpose to provide appropriate tools for comprehensiveand integrated studies.

PMID- 24873931
TI  - First-principles insights into the electronic and magnetic structure of hybrid
      organic-metal interfaces.
AB  - In this review we summarize our experience gained from several recent ab initio
      studies aimed to investigate how the competition between short-ranged chemical
      and long-ranged dispersion interactions determines the bonding mechanism of a
      specific set of chemically functionalized pi-conjugated organic molecules on non
      magnetic and magnetic metal surfaces. A key point of this review is to provide a
      detailed analysis on the issue of how to tune the strength of the organic
      molecule-surface interaction, such that the nature of the molecular bonding
      exhibits the specific electronic features of the physisorption or chemisorption
      bonding mechanisms. In particular, we discuss in detail how the precise control
      of these bonding mechanisms can be used to design specific electronic and
      magnetic properties of hybrid organic-metallic interfaces. Furthermore, our first
      principles simulations provide not only the basic insights needed to interpret
      surface-science experiments, but are also a key tool to design organic-substrate
      systems with tailored properties that can be integrated into future organic-based
      devices for molecular electronics and molecular spintronics applications. 

PMID- 24873933
TI  - GPs should go with their gut feeling when they suspect serious disease, say
      researchers.

PMID- 24873932
TI  - Genome-scale methods converge on key mitochondrial genes for the survival of
      human cardiomyocytes in hypoxia.
AB  - BACKGROUND: Any reduction in myocardial oxygen delivery relative to its demands
      can impair cardiac contractile performance. Understanding the mitochondrial
      metabolic response to hypoxia is key to understanding ischemia tolerance in the
      myocardium. We used a novel combination of 2 genome-scale methods to study key
      processes underlying human myocardial hypoxia tolerance. In particular, we
      hypothesized that computational modeling and evolution would identify similar
      genes as critical to human myocardial hypoxia tolerance. METHODS AND RESULTS: We
      analyzed a reconstruction of the cardiac mitochondrial metabolic network using
      constraint-based methods, under conditions of simulated hypoxia. We used flux
      balance analysis, random sampling, and principal component analysis to explore
      feasible steady-state solutions. Hypoxia blunted maximal ATP (-17%) and heme (
      75%) synthesis and shrank the feasible solution space. Tricarboxylic acid and
      urea cycle fluxes were also reduced in hypoxia, but phospholipid synthesis was
      increased. Using mathematical optimization methods, we identified reactions that
      would be critical to hypoxia tolerance in the human heart. We used data regarding
      single-nucleotide polymorphism frequency and distribution in the genomes of
      Tibetans (whose ancestors have resided in persistent high-altitude hypoxia for
      several millennia). Six reactions were identified by both methods as being
      critical to mitochondrial ATP production in hypoxia: phosphofructokinase,
      phosphoglucokinase, complex II, complex IV, aconitase, and fumarase. CONCLUSIONS:
      Mathematical optimization and evolution converged on similar genes as critical to
      human myocardial hypoxia tolerance. Our approach is unique and completely novel
      and demonstrates that genome-scale modeling and genomics can be used in tandem to
      provide new insights into cardiovascular genetics.

PMID- 24873934
TI  - Kondo physics in non-local metallic spin transport devices.
AB  - The non-local spin-valve is pivotal in spintronics, enabling separation of charge
      and spin currents, disruptive potential applications and the study of pressing
      problems in the physics of spin injection and relaxation. Primary among these
      problems is the perplexing non-monotonicity in the temperature-dependent spin
      accumulation in non-local ferromagnetic/non-magnetic metal structures, where the
      spin signal decreases at low temperatures. Here we show that this effect is
      strongly correlated with the ability of the ferromagnetic to form dilute local
      magnetic moments in the NM. This we achieve by studying a significantly expanded
      range of ferromagnetic/non-magnetic combinations. We argue that local moments,
      formed by ferromagnetic/non-magnetic interdiffusion, suppress the injected spin
      polarization and diffusion length via a manifestation of the Kondo effect, thus
      explaining all observations. We further show that this suppression can be
      completely quenched, even at interfaces that are highly susceptible to the
      effect, by insertion of a thin non-moment-supporting interlayer. 

PMID- 24873935
TI  - Anaphylaxis as occupational risk.
AB  - PURPOSE OF REVIEW: Anaphylaxis is a severe form of allergic reaction that may
      cause death. Main triggers of anaphylaxis have been reported to also cause
      occupational anaphylaxis (OcAn). The purpose of this article was to summarize the
      current scientific evidence on OcAn and review the specific literature published
      in 2012 and 2013. RECENT FINDINGS: Allergens derived from Hymenoptera and natural
      rubber latex are the most frequently reported triggers of OcAn, but other high
      and low-molecular weight agents have been described. Among the latter, foods,
      insects, snakes, chemicals, and medications have been described in the last 2
      years. Furthermore, reviews on the clinical significance of immunological contact
      urticaria as a risk factor for systemic allergic reaction and on Hymenoptera
      venom immunotherapy have been published. SUMMARY: OcAn is a serious event, and
      several agents and occupations have been identified as responsible. In any
      occupational setting, where there is a worker with a history of previous
      anaphylactic reactions, and in occupations at greater risk, a written emergency
      management plan of anaphylaxis episodes, along with the availability of
      adrenaline and trained personnel, are mandatory. Venom immunotherapy should be
      considered for patients with Hymenoptera venom allergy.

PMID- 24873936
TI  - Anaphylaxis and sport.
AB  - PURPOSE OF REVIEW: This article aims to review the most relevant studies on
      exercise-induced anaphylaxis, published in the last year, in order to provide
      comprehensive and updated evidence and hopefully contribute to a better
      definition of its pathophysiological mechanisms and treatment strategies. RECENT
      FINDINGS: The search strategy was performed from 1/2/2013 to 31/1/2014 by
      scanning the principal electronic bibliographic database and by hand-searching
      the main scientific publications in Allergy and Clinical Immunology. Among the
      identified articles, 17 articles were selected to be part of the systematic
      review. Eligible studies included five experimental trials, eight case reports
      and four letters. SUMMARY: The overall collected evidence was of very low
      quality. No randomized controlled trials were identified by the searching
      process. Most of the data derived from reports performed in small population
      samples or even in individual cases. Except for one article addressing issues
      related to the preventive management of exercise-induced anaphylaxis, all other
      articles focused on prevalence rates, causative triggers and pathogenetic
      mechanisms. More interesting findings were related to the influence of the IL-4
      C590T polymorphism on the onset of wheat-dependent exercise-induced anaphylaxis
      and to the usefulness of the immuno solid-phase allergen chip technique in the
      allergic screening of polysensityzed athletes at risk of severe reactions.

PMID- 24873937
TI  - Anaphylaxis: still a ghost behind allergen immunotherapy.
AB  - PURPOSE OF REVIEW: Allergen immunotherapy has been shown to be an effective
      treatment for respiratory allergies and Hymenoptera venom allergy. However,
      concern regarding its potential to cause anaphylaxis may limit its use. This
      review aims to assess whether anaphylaxis is still a worry when administering
      subcutaneous (SCIT) and sublingual immunotherapy (SLIT). RECENT FINDINGS:
      Retrospective surveillance surveys and one ongoing North American prospective
      study have helped to characterize the incidence and risk factors for fatal and
      nonfatal systemic reactions to SCIT. The latest rate of very severe, World
      Allergy Organization grade 4, systemic reactions was similar to the previously
      reported rates of near-fatal reactions, that is, 1 in 1 million injections.
      Regarding SLIT, no fatalities have been reported. Case reports of anaphylaxis in
      clinical practice and in some clinical trials have been described; however, given
      the number of doses administered daily throughout the world, the number is very
      small. SUMMARY: Identification of possible risk factors and the introduction of
      safety guidelines and practice parameters have enabled the reduction in
      immunotherapy related systemic reactions. However, it is important that
      clinicians remain vigilant when administering immunotherapy and should be
      prepared to provide emergency treatment if required.

PMID- 24873939
TI  - [Access to cancer care: the cost of treatment matters].
AB  - The approval of new antiviral agents and the wide-ranging costs of ophthalmic
      therapies with comparable efficacy have renewed the debate over the cost
      effectiveness of novel drugs. In oncology, more expensive treatments do not
      always substantially change the outcome of the disease, but they merely prolong
      life expectancy by a few weeks even at the cost of significant side effects.
      Treatment costs are a key factor the physician should consider when sharing care
      decisions with the patient. In addition, fund allocation for purchasing high cost
      medications results in limited investment in clinical research and human
      resources - doctors, nurses and other healthcare staff - that play a central role
      in patient care. Regulatory agencies should be more demanding, reimbursing
      pharmaceutical companies on the basis of treatment outcome. 

PMID- 24873940
TI  - [Access to research data: a light at the end of the tunnel?].
AB  - The recent update of a systematic review conducted by a group of researchers from
      the Cochrane Collaboration showed modest effectiveness of neuraminidase
      inhibitors in reducing hospitalizations in patients with influenza, and an even
      smaller impact of these drugs on overall mortality. However, the relevance of
      this systematic review mainly relies on the revolutionary methodology with which
      it was performed, as it included among the evidence considered findings from
      unpublished clinical study reports submitted by pharmaceutical companies to
      regulatory agencies. The paper by Jefferson et al. published in the BMJ as well
      as the campaigns supported by the same journal open a new phase that should bring
      greater transparency in the relationship between researchers, industry and
      government to the benefit of citizens.

PMID- 24873941
TI  - [Multisystem failure: the story of antinfluenza drugs].
AB  - For the past decade decision makers worldwide have endorsed the use of
      neuraminidase inhibitors. They spent billions of pounds stockpiling the two anti
      influenza drugs oseltamivir and zanamivir from the mid-2000s as part of a global
      effort to be prepared for an influenza pandemic. When the H1N1 pandemic emerged
      in 2009 the drugs were rolled out around the globe for treatment and prevention
      of influenza and its complications. Under this spotlight, we were asked to
      conduct a systematic review for Cochrane to update evidence on their efficacy.
      What should have been a routine review got complicated as the validity of a key
      study that underpinned the evidence on efficacy was unclear. Our three and half
      year battle for data has resulted in the drug manufacturers providing us with
      full clinical study reports and unveiled a story in which no party has taken full
      responsibility for ensuring the validity of the evidence underlying its
      decisions. We hope that the publication of our systematic review of the trials,
      alongside all the source clinical study reports, will change the way such
      decisions are made. 

PMID- 24873942
TI  - [Population ageing and health implication. Thinking time trends in Emilia-Romagna
      Region].
AB  - Ageing is doubtless a factor characterizing population in Europe, and
      particularly in Emilia-Romagna, a north-east Italian region of about 4,5 million
      people. From 1990 to 2010 life expectancy in Emilia-Romagna has grown by about 6
      years for men and 5 for women. At the same time good health life expectancy has
      grown even more rapidly, particularly among women. While it is expected that in
      2030 the number of over-65s will have exceeded one million people, the trends in
      good health life expectancy is not granted. Strengthen actions aimed at
      increasing good health conditions promotes ageing sustainability and can feed the
      positive trend observed for the life expectancy in good health. The Emilia
      Romagna Region takes up the demographic challenge of the coming years in the
      European context and promotes strategies for active and healthy ageing, working
      on prevention in its broadest sense and for the entire life span, with the aim of
      actively contribute to the achievement of the EU2020 target of an increase of two
      years in life expectancy in good health of European citizens. 

PMID- 24873944
TI  - [Telemedicine and wireless devices in heart failure].
AB  - Telemedicine has the potential to constitute the central element of the future
      primary care and become an effective means of prevention and early warning of
      acute exacerbation of chronic diseases. Up to now, the application of
      telemedicine has found a variety of difficulties, regarding the types and methods
      of acquisition and transmission of biological signals, the acceptance and
      cooperation of the patient, etc. The latest technological developments involve
      the combined use of wireless technologies and smartphones, for the collection and
      the transmission of data, and specific softwares for their automatic analysis.
      This paper examines some of the critical aspects in the application of new
      technologies for heart failure remote management. 

PMID- 24873943
TI  - [Cancer on the big screen. How and when movies deal with oncological diseases].
AB  - Films that feature characters with cancer have become a familiar sight for movie
      goers. 148 movies treating tumors were selected, produced all over the world
      since the Thirties, in which cancer had "prompt", "relevant", or "plot"
      character. In order to clearly understand each film's peculiar message about
      cancer, we recollected data such as genealogy, year and country of production,
      main characters' age and gender, and kind of tumor. Movies deal with cancer
      through very relevant questions, as well as themes and contexts that have great
      influence on oncologist's mind and consciousness. Specially in recent years,
      films have tackled some of the most important issues around cancer, such as his
      epidemiology and environmental causes; the economic implications of therapies;
      the management of symptoms and side effects; the psychological dynamics; the care
      toward the ending of life. The most frequent treatment mentioned in the movies
      was chemotherapy followed by antalgic therapy. Very often the ill person on the
      screen doesn't get over the disease and his death is somehow useful to the plot's
      outcome. This pattern is so strongly standardized that it persists in spite of
      real progress of treatments. Movies use disease, and other tragedies, as a
      dramatic device, and since drama is what we expect of the medium, should we be
      concerned that there is a gap between fiction and reality? Movies represent an
      essential step of educational process, but their potential has been fully
      exploited only in recent times. By watching movies on cancer, oncologists could
      become more conscious of problems they are already facing in the therapeutic
      setting: cancer and sexuality, the relationship between the ill person and the
      medical staff, side effects of therapies. Some films simply make us reflect upon
      the meaning of life and death. This is useful for the sharing of cancer care,
      from personal or familiar problems to issues of collective relevance. 

PMID- 24873945
TI  - [Movies and medicine].

PMID- 24873946
TI  - [Medicine and literature: an anthology].

PMID- 24873947
TI  - Nutrient sensing and signalling in the gastrointestinal tract.

PMID- 24873948
TI  - BRAF V600 co-testing in thyroid FNA cytology: short-term experience in a large
      cancer centre in the UK.
AB  - AIMS: To ascertain whether BRAF V600 mutational analysis is useful for diagnosis
      of thyroid cancer in thyroid fine needle aspirate (FNA). METHODS: Over 8 months
      thyroid FNAs reported as Thy 3F (neoplasm possible/suggestive of follicular
      neoplasm), Thy4 (suspicious of malignancy) and Thy 5 (malignant) were tested for
      BRAF V600 mutation and managed as malignant if mutations were present. RESULTS:
      Of 207 FNAs from 176 patients, 5 were Thy 5, 19 Thy 4, 36 Thy 3f, 13 Thy 3a, 84
      Thy 2 and 50 Thy 1. 11 Thy 3f, 15 Thy 4 and 3 Thy 5 FNAs were tested for BRAF
      V600 mutation. 0 Thy 3F cases, 6 Thy 4 and 1 Thy 5 (24% of the total tested)
      showed evidence of mutation. Four patients with BRAF V600 mutation underwent
      surgery to remove all thyroid tissue, two patients received a lobectomy and one
      patient is awaiting thyroidectomy. All patients with BRAF V600 mutation were
      found to have malignancy on final histology, with a diagnostic sensitivity for
      malignancy excluding coincidental microcarcinoma of 43% and specificity of 100%.
      CONCLUSIONS: BRAF V600 mutational analysis can enable single-stage total
      thyroidectomy for carcinoma if gene mutation is present in preoperative FNA. BRAF
      V600 co-testing may reduce the need for completion thyroidectomy with implied
      cost savings and lower patient morbidity associated with completion thyroidectomy
      when the cytology is inconclusive but where BRAF V600 mutation is identified in
      preoperative thyroid FNA.

PMID- 24873949
TI  - Waveforms for optimal sub-keV high-order harmonics with synthesized two- or three
      colour laser fields.
AB  - High-order harmonics extending to the X-ray region generated in a gas medium by
      intense lasers offer the potential for providing tabletop broadband light sources
      but so far are limited by their low conversion efficiency. Here we show that
      harmonics can be enhanced by one to two orders of magnitude without an increase
      in the total laser power if the laser's waveform is optimized by synthesizing two
      or three-colour fields. The harmonics thus generated are also favourably phase
      matched so that radiation is efficiently built up in the gas medium. Our results,
      combined with the emerging intense high-repetition MHz lasers, promise to
      increase harmonic yields by several orders to make harmonics feasible in the near
      future as general bright tabletop light sources, including intense attosecond
      pulses. 

PMID- 24873953
TI  - Ontogenetic changes of the soluble and membrane-bound D2 glycoprotein in rat
      forebrain.
AB  - A soluble form of the D2 glycoprotein, detected in the rat brain hypotonic
      extract, is described. Its specific relative concentration did not differ
      significantly in the three examined cerebral regions (forebrain, brainstem and
      cerebellum), while in the cerebellum the membrane-bound form was about three and
      four times more concentrated than in the forebrain and brainstem, respectively.
      No sizeable developmental variations of the soluble D2 concentration could be
      detected in forebrain, whereas the amount of the membrane-bound protein rose from
      birth to postnatal day 6 and then decreased to the adult value (about 40% of the
      newborn concentration). Ontogenetic modifications of the membranous D2 glycans
      (studied through the binding of the molecule to several lectins) occur around
      postnatal day 18 when the binding to Ricinus communis lectin, specific for
      galactose, becomes evident. At all ages both soluble and membrane-bound forms
      bind to Concanavalin A, specific for mannose and glucose, and to wheat germ
      agglutinin, specific for N-acetylglucosamine, while the lack of binding to Ulex
      europeus lectin suggests the absence of discrete amount of fucose. The results
      are discussed in relation to the possible involvement of D2 glycoprotein in cell
      to-cell adhesion. 

PMID- 24873952
TI  - Rigid 2',4'-difluororibonucleosides: synthesis, conformational analysis, and
      incorporation into nascent RNA by HCV polymerase.
AB  - We report on the synthesis and conformational properties of 2'-deoxy-2',4'
      difluorouridine (2',4'-diF-rU) and cytidine (2',4'-diF-rC) nucleosides. NMR
      analysis and quantum mechanical calculations show that the strong
      stereoelectronic effects induced by the two fluorines essentially "lock" the
      conformation of the sugar in the North region of the pseudorotational cycle. Our
      studies also demonstrate that NS5B HCV RNA polymerase was able to accommodate
      2',4'-diF-rU 5'-triphosphate (2',4'-diF-rUTP) and to link the monophosphate to
      the RNA primer strand. 2',4'-diF-rUTP inhibited RNA synthesis in dinucleotide
      primed reactions, although with relatively high half-maximal inhibitory
      concentrations (IC50 > 50 MUM). 2',4'-diF-rU/C represents rare examples of
      "locked" ribonucleoside mimics that lack a bicyclic ring structure. 

PMID- 24873951
TI  - Raman optical activity of a cyclic dipeptide analyzed by quantum chemical
      calculations combined with molecular dynamics simulations.
AB  - Raman optical activity (ROA) measures the different intensity of right- and left
      circularly polarized Raman scattered light and provides information on chirality
      associated with vibrational modes. Because of a high sensitivity to subtle
      structural and environmental changes, interpretations of ROA spectra usually rely
      on quantum chemical simulations. Recent advances in computational chemistry allow
      us to consider explicit solvent models that are derived from molecular dynamics
      (MD) simulations to compute the Raman and ROA spectra. An important concern for
      the explicit solvent models is the number of MD snapshots that lead to a good
      agreement between the observed and calculated spectra. In the present study, we
      measured the Raman and ROA spectra of cyclo(L-Ala-Gly) and then simulated the
      spectra using density functional theory combined with MD simulations. Although
      cyclo(L-Ala-Gly) is a relatively rigid cyclic molecule, boat-up and boat-down
      conformations were found from the MD calculations. Because the Raman spectra of
      the two conformations are similar except for a lower frequency region, ~10 MD
      snapshots are capable of reproducing the main features of the observed Raman
      spectra. In contrast, a larger number of MD snapshots was required to reproduce
      the ROA spectra. In the middle freqency region of 800-1580 cm(-1), an average of
      ~40 spectra led to good agreement between the observed and calculated spectra. On
      the other hand, the low (0-800 cm(-1)) and high (1580-1800 cm(-1)) frequency
      regions require more than 60 and 120 MD snapshots, respectively. The Raman and
      ROA spectra in the low frequency region are relatively broad, and such spectral
      features require a larger number of averaged spectra. The high frequency region
      of the spectra consists of an amide I band, which is primarily a C?O stretching
      vibration. Since both the ROA intensity and frequency of the amide I band are
      highly sensitive to structural and environmental differences, a large number of
      the spectra need to be averaged to reproduce the small negative features in the
      observed ROA spectra.

PMID- 24873950
TI  - The microfluidic multitrap nanophysiometer for hematologic cancer cell
      characterization reveals temporal sensitivity of the calcein-AM efflux assay.
AB  - Cytometric studies utilizing flow cytometry or multi-well culture plate
      fluorometry are often limited by a deficit in temporal resolution and a lack of
      single cell consideration. Unfortunately, many cellular processes, including
      signaling, motility, and molecular transport, occur transiently over relatively
      short periods of time and at different magnitudes between cells. Here we
      demonstrate the multitrap nanophysiometer (MTNP), a low-volume microfluidic
      platform housing an array of cell traps, as an effective tool that can be used to
      study individual unattached cells over time with precise control over the
      intercellular microenvironment. We show how the MTNP platform can be used for
      hematologic cancer cell characterization by measuring single T cell levels of
      CRAC channel modulation, non-translational motility, and ABC-transporter
      inhibition via a calcein-AM efflux assay. The transporter data indicate that
      Jurkat T cells exposed to indomethacin continue to accumulate fluorescent calcein
      for over 60 minutes after calcein-AM is removed from the extracellular space. 

PMID- 24873954
TI  - Development of immunoreactive lhrh neurons in the fetal rat hypothalamus.
AB  - The ontogenesis of immunoreactive (ir) LHRH neurons was investigated in rats
      applying the double-bridge PAP method of Vacca et al. (J. Histochem. Cytochem.
      28, 297-307, 1980). Ir LHRH was first evident in the cell bodies confined in the
      ventromedial surface of the anterior part of the forebrain vesicles on day 16.5
      of gestation. Only one or two cells, if any, were found in the brains examined;
      the cells are oval showing ir brown granules within the perikarya and also within
      the processes extended from both poles. On day 17.5 of gestation, a few ir cells
      appeared in the olfactory cortex, medial septum, medial preoptic area, diagonal
      band of Broca, and ventro-lateral surface of the anterior hypothalamus, and, with
      development, their numbers increased gradually. During the prenatal period, no ir
      cell exists in the arcuate nucleus or in the medial-basal hypothalamus. Beaded ir
      fibers appeared in the organum vasculosum of the lamina terminalis (OVLT) and in
      the external layer of the median eminence on 18.5 and 19.5 days of gestation,
      respectively. The present findings ascertain that the hypothalamic regulation of
      hypophysial gonadotrophic function exists during fetal period in rats. 

PMID- 24873955
TI  - Retinal degeneration in primates raised on a synthetic human infant formula.
AB  - A degeneration of the retinal cone photoreceptor cells, but not of the rod
      photoreceptor cells, is present in rhesus monkeys raised from birth for 26 months
      on a commercially available human infant protein hydrolyzate formula. This
      degeneration is associated with a selective decrease in plasma taurine
      concentration, and is entirely prevented by supplementing the formula with
      taurine. A reduced conedominated ERG was present at 10 months, but not at 18 or
      26 months. These results suggest that the implications of the reduced taurine
      concentrations in human infants fed synthetic formulas containing little or no
      taurine should be reconsidered, since adverse effects on the visual system may
      only be detectable at the ultrastructural level. 

PMID- 24873956
TI  - Influence of brain extract and dibutyryl cyclic AMP on the amount of carbonic
      anhydrase in primary glial cell cultures from newborn rat brain.
AB  - The effect of brain extracts from rat and beef, and of 2',5'-dibutyryl cyclic AMP
      on the CAII content was investigated in rat primary glial cultures maintained in
      serum-containing or serum-free medium. All cultures contained a mixed population
      of oligodendroglial and astroglial cells, but under certain conditions the
      cultures were highly enriched in oligodendroglial cells. An immunocytochemical
      positive reaction to CAII was observed in oligodendrocytes, while astrocytes were
      not stained. The content of CAII per culture and per oligodendroglial cell was
      higher after treatment of the culture with soluble brain extract and a partially
      purified fraction. A combined autoradiographic- immunohistochemical study, after
      [(3)H]thymidine incorporation and staining for CAII, showed that under the
      influence of rat brain extract the number of mitotic CAII positive cells was
      greater at day 11 compared to control cultures. But the proliferation rate
      decreased with time in culture after brain extract treatment and the number of
      mitotic CAII positive cells became far below that of controls. Since at the same
      time CAII quantity per cell was higher in the treated ones it is suggested that
      brain extract not only influences the proliferation of oligodendroglial cells,
      but also their maturation. The addition of 2' ,5'-dibutyryl cyclic AMP had no
      effect on oligodendroglial cells and the amount of CAII in the cultures was not
      affected. It is discussed that agents, which stimulate 3',5'-cyclic AMP content,
      may not influence the CAII content, but may stimulate the enzymatic activity. 

PMID- 24873957
TI  - In vivo uptake of heterologous alphafetoprotein and serum albumin by ependymal
      cells of developing chick embryos.
AB  - The in vivo uptake by neuroepithelial cells of rat serum proteins injected into
      the mesencephalic cavity of developing chicken was demonstrated by
      immunohistochemical methods. It was found that 48 h after inoculation, rat
      alphafetoprotein (AFP) and serum albumin (SA) localize in the same places as do
      chicken AFP and SA. No labelling was present for rat or chicken IgG. We also
      present evidence showing that chicken ovalbumin, which is not normally found
      inside ependymal cells is not internalized even when injected into the
      cerebrospinal fluid at 30-fold its physiological concentration. The existence of
      transient specific receptors which could be responsible for this protein uptake
      is proposed. The possible implications in relation to developmental biology are
      discussed. 

PMID- 24873958
TI  - Muscarinic receptor regulation in the sympathetically innervated avian expansor
      secundariorum.
AB  - We sought to examine further the regulation of muscarinic receptors in the
      developing expansor secundariorum, a smooth muscle of the avian wing.
      [(3)H]Quinuclidinyl benzilate binding was used as a measure of muscarinic
      receptors present in the muscle, which gradually decline in density from hatch
      during the following few weeks. Receptor loss can be prevented by denervation of
      the muscle immediately after hatch, but receptor density is not recovered by
      denervation in older birds. As the major innervation is provided by sympathetic,
      noradrenergic fibres with no evidence of a cholinergic input, the action of
      several pharmacological agents known to affect noradrenergic transmission was
      examined. Reserpine partially prevented the early receptor decline but
      phenoxybenzamine and dimethylphenylpiperazinium did not significantly affect
      receptor density. The muscle was also immobilized by tenotomy, since this unique
      muscle is attached to the shoulder by a long, discrete tendon. Tenotomy
      significantly retarded the normal developmental receptor loss. It is suggested
      that in this muscle, muscarinic receptor density is regulated by noradrenergic
      nerves, possibly by a mechanism involving the transmitter, noradrenaline. 

PMID- 24873959
TI  - Ornithine decarboxylase and polyamines in developing rat brain and heart: Effects
      of perinatal hypothyroidism.
AB  - Hypothyroidism induced by perinatal administration of propylthiouracil (PTU) had
      profound effects on growth of the heart, with major organ weight deficits
      persisting well beyond the termination of drug treatment. These effects were
      preceded by disruption of the developmental patterns of cardiac ornithine
      decarboxylase (ODC) and the polyamines, which are thought to be intracellular
      modulators of cellular maturation. Activity of cardiac ODC was depressed in the
      PTU-treated group and putrescine and spermidine levels were markedly subnormal.
      PTU administration also affected brain growth, but much less so than in the
      heart. The disruption of the brain ODC/polyamine system was also less pronounced,
      with relatively small degrees of spermidine depletion and a slight elevation of
      ODC. For both tissues, the biochemical effects of perinatal hypothyroidism were
      opposite to those found previously for administration of exogenous thyroid
      hormones. These results support the views that: 

PMID- 24873960
TI  - Neurogenesis in the rat neostriatum.
AB  - Neurogenesis in the rat neostriatum was examined with [(3)H]thymidine
      autoradiography. For the animals in the prenatal groups, the initial
      [(3)H]thymidine exposures were separated by 24 h; they were the offspring of
      pregnant females given two injections on consecutive embryonic (E) days (E13-E14,
      E14-E15, ... E21-E22). For the animals in the postnatal (P) groups, the initial
      [(3)H]thymidine exposures were separated by 48 h, each group receiving four
      consecutive injections (P0-P3, P2-P5, P4-P7). On P60, the percentage of labeled
      cells and the proportion of cells originating during either 24 or 48 h periods
      were quantified at several anatomical levels for both the large and medium-sized
      neurons. Neurogenesis of the large neurons occurs mainly between E13 and E16 in a
      strong caudal-to-rostral gradient. The medium-sized neurons throughout the
      neostriatum are generated in a prominent ventrolateral-to-dorsomedial gradient so
      that ventrolateral cells originate mainly between E14 and E18, dorsomedial cells
      between E18 and E21-22 (fewer than 10% originate between P0 and P4). Medium-sized
      neurons also show two other gradients. First, there is a superficial-to-deep
      gradient in the anterior part of the caudoputamen, while more posterior levels
      have a deep-to-superficial gradient. Second, anterior parts have a caudal-to
      rostral gradient while posterior parts have a gradient in the opposite direction.
      This shift in neurogenetic gradients along both superficial-deep and rostrocaudal
      directions is developmental evidence that an anterior 'caudate' can be separated
      from a posterior 'putamen' in the rat. Finally, neurogenetic gradients in the
      medium-sized caudoputamen neurons can be linked to the patterns of their
      anatomical interconnections with the substantia nigra. 

PMID- 24873962
TI  - Morphometry of GFA and vimentin positive astrocytes in grafted and lesioned
      cortex cerebri.
AB  - The presence and morphology of GFA- and vimentin-positive astrocytes were studied
      immunohistochemically in rats using smear preparations of single intraocular
      grafts of the cortex cerebri anlage and of cortex pieces grafted to eyes
      containing a previously grafted piece of the locus coeruleus area. Similarly,
      astrocytes were studied in lesioned cortex cerebri in situ. A high number of GFA
      and vimentin-positive cells were found in smears of both types of cortex grafts
      as well as in smears of the lesioned cortex cerebri in situ. In contrast, only a
      limited number of GFA-positive astrocytes were seen in smears of normal cortex.
      Using computerized image analysis, the two-dimensional cell area and cell
      perimeter were found to be significantly increased in individual GFA-positive
      astrocytes in both types of intraocular cortex grafts as well as in the lesioned
      cortex when compared to GFA-positive astrocytes in normal cortex cerebri. GFA
      positive cells in smears of cortex grafts from locus coeruleus-cortex
      combinations had significantly smaller cell area and cell perimeter values
      compared to similar cells from single cortex grafts. A similar, although less
      pronounced difference was observed between vimentin-positive cells from the same
      type of grafts. This suggests that the presence of the mature locus coeruleus
      graft in some as yet unknown way influences the development of the adjacent
      cortex graft towards a more normal astrocytic maturation. An additional finding
      was the large size difference between GFA- and vimentin-positive cells in the
      intraocular grafts. Since most evidence indicates that vimentin-positive cells
      are also GFA-positive, this may indicate that the two intermediate filament
      systems have a partially different distribution within individual astrocytes. It
      is concluded that computerized image analysis of smears processed for
      immunohistochemistry with antisera against GFA and vimentin is a useful technique
      for studies of astrocyte morphology in normal as well as experimentally perturbed
      CNS tissue. Cortex tissue that develops in contact with a locus coeruleus graft
      in the eye chamber show a significantly lesser degree of gliosis than cortex
      tissue developing in isolation in the eye. 

PMID- 24873961
TI  - High ciliary neuronotrophic specific activity in rat peripheral nerve.
AB  - Ciliary neuronotrophic factors (CNTFs) are proteins defined by their ability to
      promote the survival in tissue culture of chick embryo ciliary ganglionic
      neurons. CNTF activity has been reported in several source materials. Among these
      sources, the highest specific activity, i.e. 16,000 TU/mg, has been found in the
      intraocular tissue innervated by the ciliary ganglionic neurons. We now report
      that extracts of adult rat peripheral nerve and spinal nerve roots contain CNTF
      at a specific activity equal to or greater than the intraocular tissue. Equally
      high concentrations of CNTF activity are found in both motor and sensory nerves.
      The possible cellular source(s) of this mammalian CNTF is discussed. 

PMID- 24873963
TI  - Cultured embryonic non-innervated mouse muzzle is capable of generating a whisker
      pattern. Int. J. Neurosci. Andres F.L. and Van der Loos H. (1984) 1, 319-338.

PMID- 24873964
TI  - High-performance thin-layer chromatography analysis of steviol glycosides in
      Stevia formulations and sugar-free food products, and benchmarking with (ultra)
      high-performance liquid chromatography.
AB  - A high-performance TLC (HPTLC) method was newly developed and validated for
      analysis of 7 steviol glycosides in 6 different types of food and Stevia
      formulations. After a minimized one-step sample preparation, 21 samples were
      developed in parallel, allowing an effective food screening. Depending on the
      sample application volume, the method was suited to analyze food sample
      concentrations in the mg/kg range. LOQs of stevioside in natural yoghurt matrix
      spiked at 0.02, 0.13 and 0.2% were determined by the calibration curve method to
      be 12ng/band (peak height). ANOVA was successfully passed to prove data
      homogeneity in the working range (30-600ng/band). The accuracy (recovery
      tolerance limit, 92-120%), repeatability (3.1-5.4%) and intermediate precision
      (4.0-8.4%) were determined for stevioside in milk-based matrix including sample
      preparation and recovery rates at 3 different concentration levels. For the first
      time, the recording of HPTLC-ESI-MS spectra via the TLC-MS Interface was
      demonstrated for rebaudioside A. HPTLC contents for rebaudioside A were compared
      with results of two (U)HPLC methods. The running costs and analysis time of the
      three different methods were discussed in detail with regard to screening of food
      products. 

PMID- 24873965
TI  - Evaluation of the retention pattern on ionic liquid columns for gas
      chromatographic analyses of fatty acid methyl esters.
AB  - Fatty acid methyl esters from marine sources were analyzed by gas chromatography
      mass spectrometry on three ionic liquid columns, SLB-IL61, SLB-IL82 and SLB-IL100
      (Supelco). Retention indices (equivalent chain lengths) are reported for more
      than 100 compounds and the overlap patterns are evaluated from these data. The
      influence of chromatographic conditions on the retention indices of unsaturated
      fatty acid methyl esters is also evaluated. Compared to typical alternative
      phases the retention patterns on all three columns are highly dependent on the
      conditions. The SLB-IL61 phase had overlaps between nutritionally important fatty
      acids that could not be resolved by changing the chromatographic conditions. This
      column is therefore regarded as unsuitable for clinical and nutritional studies
      of the fatty acid composition, but similar overlaps may be avoided on IL82 and
      IL100. On all three columns double bonds close to the carboxyl group in the
      analytes contribute with limited retention, which makes it challenging to predict
      the retention of polyunsaturated fatty acid methyl esters. 

PMID- 24873966
TI  - Pentaarylbiimidazole, PABI: an easily synthesized fast photochromic molecule with
      superior durability.
AB  - We report a new type of fast photochromic imidazole dimer, pentaarylbiimidazole
      (PABI), which shows a few MUs fast photochromism with high fatigue resistance
      against light irradiation. PABI has an unusual spiroconjugated imidazoisoindole
      skeleton and its derivatives can be prepared by simple synthetic procedures. 

PMID- 24873969
TI  - Facile synthesis of water-soluble Au(25-x)Ag(x) nanoclusters protected by mono-
      and bi-thiolate ligands.
AB  - A series of water-soluble Au25-xAgx nanoclusters (NCs) protected by mono- and bi
      thiolate ligands are synthesized via the NaOH-mediated NaBH4 reduction method.
      Compositions of both the metal core and the ligand shell can be tailored by
      varying the feeding ratios of metal precursors and hetero-ligands, further
      enriching the functionalities of the NCs. 

PMID- 24873967
TI  - Prevalence of HIV, HSV-2 and pregnancy among high school students in rural
      KwaZulu-Natal, South Africa: a bio-behavioural cross-sectional survey.
AB  - OBJECTIVE: Adolescents in southern African high schools are a key population for
      HIV prevention interventions. We report on the prevalence of HIV, HSV-2 and
      pregnancy as indicators of high-risk sexual behaviour among high school students
      in rural KwaZulu-Natal. DESIGN: Bio-behavioural cross-sectional survey. METHODS:
      Students completed a self-administered structured, standardised demographic and
      sexual behavioural questionnaire. Dried blood spot specimens were collected for
      HIV and HSV-2 testing. Urine specimens were used for pregnancy testing in female
      students. RESULTS: A total of 2675 (1423 females, 1252 males) consenting students
      were enrolled from 14 high schools between September and November 2010. The
      median age of students was 16 years (IQR 15-18). HIV prevalence was 1.4% (95% CI
      0.9 to 1.9) in males and 6.4% (95% CI 4.6 to 8.3) in females (p<0.001). HSV-2
      prevalence was 2.6% (95% CI 1.6 to 3.7) in males and 10.7% (95% CI 8.8 to 12.6)
      in females (p<0.001). Pregnancy prevalence was 3.6% (95% CI 2.6 to 4.5). Risk
      factors for prevalent HIV infection in female students included being over 18
      years of age (adjusted OR (aOR)=2.67, 95% CI 1.67 to 4.27; p<0.001), prevalent
      HSV-2 infection (aOR=4.35, 95% CI 2.61 to 7.24; p<0.001), previous pregnancy
      (aOR=1.66, 95% CI 1.10 to 2.51; p=0.016) and experience of two or more deaths in
      the household in the previous year (aOR=1.97, 95% CI 1.13 to 3.44; p=0.016).
      CONCLUSIONS: The high prevalence of HIV, HSV-2 and pregnancy underscore the need
      for school-based sexual and reproductive health services, and provide further
      impetus for the inclusion of adolescents in behavioural and biomedical trials
      with HIV incidence endpoints.

PMID- 24873971
TI  - Ecohydrodynamics of cold-water coral reefs: a case study of the Mingulay Reef
      Complex (western Scotland).
AB  - Ecohydrodynamics investigates the hydrodynamic constraints on ecosystems across
      different temporal and spatial scales. Ecohydrodynamics play a pivotal role in
      the structure and functioning of marine ecosystems, however the lack of
      integrated complex flow models for deep-water ecosystems beyond the coastal zone
      prevents further synthesis in these settings. We present a hydrodynamic model for
      one of Earth's most biologically diverse deep-water ecosystems, cold-water coral
      reefs. The Mingulay Reef Complex (western Scotland) is an inshore seascape of
      cold-water coral reefs formed by the scleractinian coral Lophelia pertusa. We
      applied single-image edge detection and composite front maps using satellite
      remote sensing, to detect oceanographic fronts and peaks of chlorophyll a values
      that likely affect food supply to corals and other suspension-feeding fauna. We
      also present a high resolution 3D ocean model to incorporate salient aspects of
      the regional and local oceanography. Model validation using in situ current
      speed, direction and sea elevation data confirmed the model's realistic
      representation of spatial and temporal aspects of circulation at the reef complex
      including a tidally driven current regime, eddies, and downwelling phenomena.
      This novel combination of 3D hydrodynamic modelling and remote sensing in deep
      water ecosystems improves our understanding of the temporal and spatial scales of
      ecological processes occurring in marine systems. The modelled information has
      been integrated into a 3D GIS, providing a user interface for visualization and
      interrogation of results that allows wider ecological application of the model
      and that can provide valuable input for marine biodiversity and conservation
      applications. 

PMID- 24873968
TI  - Deficient production of reactive oxygen species leads to severe chronic DSS
      induced colitis in Ncf1/p47phox-mutant mice.
AB  - BACKGROUND: Colitis is a common clinical complication in chronic granulomatous
      disease (CGD), a primary immunodeficiency caused by impaired oxidative burst.
      Existing experimental data from NADPH-oxidase knockout mice propose contradictory
      roles for the involvement of reactive oxygen species in colitis chronicity and
      severity. Since genetically controlled mice with a point-mutation in the Ncf1
      gene are susceptible to chronic inflammation and autoimmunity, we tested whether
      they presented increased predisposition to develop chronic colitis. METHODS:
      Colitis was induced in Ncf1-mutant and wild-type mice by a 1st 7-days cycle of
      dextran sulfate sodium (DSS), intercalated by a 7-days resting period followed by
      a 2nd 7-days DSS-cycle. Cytokines were quantified locally in the colon
      inflammatory infiltrates and in the serum. Leukocyte infiltration and
      morphological alterations of the colon mucosa were assessed by
      immunohistochemistry. RESULTS: Clinical scores demonstrated a more severe colitis
      in Ncf1-mutant mice than controls, with no recovery during the resting period and
      a severe chronic colitis after the 2nd cycle, confirmed by histopathology and
      presence of infiltrating neutrophils, macrophages, plasmocytes and lymphocytes in
      the colon. Severe colitis was mediated by increased local expression of cytokines
      (IL-6, IL-10, TNF-alpha, IFN-gamma and IL-17A) and phosphorylation of Leucine
      rich repeat kinase 2 (LRRK2). Serological cytokine titers of those inflammatory
      cytokines were more elevated in Ncf1-mutant than control mice, and were
      accompanied by systemic changes in functional subsets of monocytes, CD4+ T and B
      cells. CONCLUSION: This suggests that an ineffective oxidative burst leads to
      severe chronic colitis through local accumulation of peroxynitrites, pro
      inflammatory cytokines and lymphocytes and systemic immune deregulation similar
      to CGD.

PMID- 24873972
TI  - Yttrium and lanthanide complexes of beta-dialdehydes: synthesis, characterization
      and luminescence of coordination compounds with the conjugate base of
      nitromalonaldehyde.
AB  - Coordination compounds having formulae [AsPh4][Ln(NMA)4] (1(Ln)), Ln(NMA)3(tppo)2
      (2(Ln)), Ln(NMA)3(bipyO2) (3(Ln)), Ln(NMA)3(phen) (4(Ln)) and Ln(NMA)3(terpy)
      (5(Ln)) (Ln = Y and some lanthanides; NMA = conjugate base of nitromalonaldehyde;
      tppo = triphenylphosphine oxide; bipyO2 = 2,2'-bipyridine-N,N'-dioxide; phen =
      1,10-phenanthroline; terpy = 2,2':6',2''-terpyridine) were synthesized and
      characterized and X-ray diffraction data were collected for [AsPh4][Y(NMA)4]
      (1(Y)). The neutral europium derivatives showed appreciable luminescence in the
      solid state upon excitation with UV light and photoluminescence measurements were
      carried out. These compounds were used as dopants for the preparation of
      luminescent poly(methyl methacrylate). Luminescent polyvinylpyrrolidone samples
      were obtained by reacting the pure polymer with water solutions containing NMA
      and trivalent europium ions. 

PMID- 24873970
TI  - A dual drug sensitive L. major induces protection without lesion in C57BL/6 mice.
AB  - Leishmaniasis is a major health problem in some endemic areas and yet, no vaccine
      is available against any form of the disease. Historically, leishmanization (LZ)
      which is an inoculation of individual with live Leishmania, is the most effective
      control measure at least against cutaneous leishmaniasis (CL). Due to various
      reasons, LZ is not used today. Several live attenuated Leishmania have been
      developed but their use is limited. Previously, we developed a transgenic strain
      of L. major that harbors two suicide genes tk and cd genes (lmtkcd+/+) for use as
      a challenge strain in vaccine studies. These genes render the parasite
      susceptible to Ganciclovir (GCV) and 5-flurocytosine (5-FC). The dual drug
      sensitive strain of L. major was developed using gene targeting technology using
      a modified Herpes Simplex Virus thymidine kinase gene (hsv-tk) sensitive to
      Ganciclovir antibiotic and Saccharomyces cerevisae cytosine deaminase gene (cd
      sensitive to 5-flurocytosine) that were stably introduced into L. major
      chromosome. BALB/c mice inoculated with lmtkcd+/+ developed lesions which upon
      treatment with GCV and 5-FC completely healed. In the current study, the
      transgenic lmtkcd+/+strain was assessed as a live vaccine model to determine the
      time necessary to develop a protective immune response. C57BL/6 mice were
      inoculated with the transgenic lmtkcd+/+strain, and treated at the time of
      inoculation (day 0) or at day 8 after inoculation. Immunized animals were
      challenged with wild-type L. major, and complete protection was induced in mice
      that were treated at day 8. The results show that in contrast to leishmanization,
      in group of mice inoculated with a dual sensitive L. major development and
      persistence of lesion is not necessary to induce Th1 response and protection.

PMID- 24873974
TI  - Negative feelings and help seeking among older adults with chronic conditions.
AB  - Older adults with chronic conditions are at greater risk of negative affect,
      though few studies have focused on older adults' perspectives on how chronic
      conditions affect their mental well-being. This study involved in-depth
      interviews that explored how older adults describe their feelings about chronic
      conditions, the context within which they experience these feelings, and their
      experiences with help-seeking for negative feelings. Participants reported that
      older adults experience a range of negative feelings related to their conditions
      and are only comfortable talking to people who understand their everyday
      experiences with managing chronic conditions. The findings have implications for
      health self-management.

PMID- 24873973
TI  - Ly49C-dependent control of MCMV Infection by NK cells is cis-regulated by MHC
      Class I molecules.
AB  - Natural Killer (NK) cells are crucial in early resistance to murine
      cytomegalovirus (MCMV) infection. In B6 mice, the activating Ly49H receptor
      recognizes the viral m157 glycoprotein on infected cells. We previously
      identified a mutant strain (MCMVG1F) whose variant m157 also binds the inhibitory
      Ly49C receptor. Here we show that simultaneous binding of m157 to the two
      receptors hampers Ly49H-dependent NK cell activation as Ly49C-mediated inhibition
      destabilizes NK cell conjugation with their targets and prevents the cytoskeleton
      reorganization that precedes killing. In B6 mice, as most Ly49H+ NK cells do not
      co-express Ly49C, the overall NK cell response remains able to control
      MCMVm157G1F infection. However, in B6 Ly49C transgenic mice where all NK cells
      express the inhibitory receptor, MCMV infection results in altered NK cell
      activation associated with increased viral replication. Ly49C-mediated inhibition
      also regulates Ly49H-independent NK cell activation. Most interestingly, MHC
      class I regulates Ly49C function through cis-interactions that mask the receptor
      and restricts m157 binding. B6 Ly49C Tg, beta2m ko mice, whose Ly49C receptors
      are unmasked due to MHC class I deficient expression, are highly susceptible to
      MCMVm157G1F and are unable to control a low-dose infection. Our study provides
      novel insights into the mechanisms that regulate NK cell activation during viral
      infection. 

PMID- 24873978
TI  - Concurrent administration of an intranasal vaccine containing feline herpesvirus
      1 (FHV-1) with a parenteral vaccine containing FHV-1 is superior to parenteral
      vaccination alone in an acute FHV-1 challenge model.
AB  - The administration of intranasal (IN) or subcutaneous (SC) vaccines containing
      modified live feline herpesvirus 1 (FHV-1) offers some level of protection
      against FHV-1 challenge, but relative efficacy is <100%. In this study, clinical
      signs and viral shedding in kittens were compared among three groups: (1) kittens
      vaccinated concurrently with IN and SC vaccines containing FHV-1 (Group 1, n =
      8); (2) kittens vaccinated with a SC FHV-1 vaccine alone (Group 2, n = 8), and
      (3) unvaccinated control kittens (Group 3, n = 8). All kittens were FHV-1 naive
      at enrolment, and challenge with a virulent strain of FHV-1 was performed 1 week
      after vaccination. Daily clinical signs and pharyngeal FHV-1 shedding were
      recorded over a 21-day infection period. Overall, kittens in Group 1 had
      significantly less severe clinical illness than those in Group 2 (P < 0.05).
      Additionally, significantly less FHV-1 DNA was detected on pharyngeal swabs from
      kittens in Group 1 compared to those in Group 2 (P < 0.001). Concomitant
      administration of IN and SC FHV-1 vaccines was superior to administration of the
      SC FHV-1 vaccine alone in this challenge model of FHV-1 naive kittens.

PMID- 24873979
TI  - [Inappropriate use of urinary catheters in patients admitted to medical wards:
      experience in a local hospital and strategies for reducing their use].

PMID- 24873980
TI  - [Serotoninergic syndrome due to linezolid and metoclopramide].

PMID- 24873981
TI  - [Can the use of antibiotics be improved in outpatients in Spain?].

PMID- 24873982
TI  - [Community-acquired invasive soft tissue infections due to Streptococcus
      pyogenes].

PMID- 24873983
TI  - Emerging pattern mining to aid toxicological knowledge discovery.
AB  - Knowledge-based systems for toxicity prediction are typically based on rules,
      known as structural alerts, that describe relationships between structural
      features and different toxic effects. The identification of structural features
      associated with toxicological activity can be a time-consuming process and often
      requires significant input from domain experts. Here, we describe an emerging
      pattern mining method for the automated identification of activating structural
      features in toxicity data sets that is designed to help expedite the process of
      alert development. We apply the contrast pattern tree mining algorithm to
      generate a set of emerging patterns of structural fragment descriptors. Using the
      emerging patterns it is possible to form hierarchical clusters of compounds that
      are defined by the presence of common structural features and represent distinct
      chemical classes. The method has been tested on a large public in vitro
      mutagenicity data set and a public hERG channel inhibition data set and is shown
      to be effective at identifying common toxic features and recognizable classes of
      toxicants. We also describe how knowledge developers can use emerging patterns to
      improve the specificity and sensitivity of an existing expert system. 

PMID- 24873984
TI  - Working memory deficits in developmental dyscalculia: The importance of serial
      order.
AB  - Although a number of studies suggests a link between working memory (WM) storage
      capacity of short-term memory and calculation abilities, the nature of verbal WM
      deficits in children with developmental dyscalculia (DD) remains poorly
      understood. We explored verbal WM capacity in DD by focusing on the distinction
      between memory for item information (the items to be retained) and memory for
      order information (the order of the items within a list). We hypothesized that WM
      for order could be specifically related to impaired numerical abilities given
      that recent studies suggest close interactions between the representation of
      order information in WM and ordinal numerical processing. We investigated item
      and order WM abilities as well as basic numerical processing abilities in 16
      children with DD (age: 8-11 years) and 16 typically developing children matched
      on age, IQ, and reading abilities. The DD group performed significantly poorer
      than controls in the order WM condition but not in the item WM condition. In
      addition, the DD group performed significantly slower than the control group on a
      numerical order judgment task. The present results show significantly reduced
      serial order WM abilities in DD coupled with less efficient numerical ordinal
      processing abilities, reflecting more general difficulties in explicit processing
      of ordinal information.

PMID- 24873985
TI  - Using pulmonary imaging to move chronic obstructive pulmonary disease beyond
      FEV1.
AB  - FEV1, measured using spirometry, provides a straightforward, widely available,
      and inexpensive global measurement of airflow limitation and lung function. For
      decades, FEV1 has remained the main intermediate endpoint used in research
      studies and for the development of new chronic obstructive pulmonary disease
      (COPD) therapies. Not surprisingly, treatments that acutely improve FEV1 dominate
      as COPD therapies. However, in patients with COPD, the relationship of FEV1 with
      symptoms and outcomes such as exacerbations and mortality is weak, and,
      importantly, FEV1 does not take into account the heterogeneity of COPD or its
      different phenotypes. Thoracic imaging provides a way to quantify airway
      remodeling, emphysematous destruction, regional ventilation abnormalities
      (ventilation defects), and gas trapping in ex-smokers in whom FEV1 may be normal
      and in patients with COPD with very modest lung function deterioration. In
      individual patients and in COPD cohort studies, thoracic imaging using X-ray
      computed tomography, and magnetic resonance imaging (conventional (1)H as well as
      hyperpolarized noble gases such as (129)Xe, (3)He, and inhaled O2 and (19)F) can
      be used to directly visualize the structural and functional consequences of COPD
      and thus provide a clearer picture of COPD mechanisms, disease progression, and
      response to therapy. We briefly describe pulmonary imaging methods that provide a
      way to visualize and quantify, with high spatial and temporal resolution,
      regional ventilation abnormalities, gas trapping, emphysema, and airway
      remodeling in COPD. Finally, we discuss the implications of recent imaging
      findings and their impact on future biomarker and therapy research aimed at
      improving COPD outcomes. 

PMID- 24873986
TI  - Co-administration of a meningococcal glycoconjugate ACWY vaccine with travel
      vaccines: a randomized, open-label, multi-center study.
AB  - BACKGROUND: Potential interactions between vaccines may compromise the
      immunogenicity and/or safety of individual vaccines so must be assessed before
      concomitant administration is recommended. In this study, the immunogenicity and
      safety of travel vaccines against Japanese encephalitis (JEV) and rabies (PCECV)
      administered together with or without a quadrivalent meningococcal glycoconjugate
      ACWY-CRM vaccine were evaluated (NCT01466387). METHOD: Healthy adults aged 18 to
      <=60 years were randomized to one of four vaccine regimens: JEV + PCECV + MenACWY
      CRM, JEV + PCECV, PCECV or MenACWY-CRM. Immunogenicity at baseline and 28 days
      post-complete vaccination was assessed by serum bactericidal assay using human
      complement or neutralization tests. Adverse events (AEs) were collected
      throughout the study period. RESULTS: JEV + PCECV + MenACWY-CRM was non-inferior
      to JEV + PCECV. Post-vaccination seroprotective neutralizing titers or
      concentrations were achieved in 98-99% (JE) and 100% (rabies) of subjects across
      the vaccine groups. Antibody responses to vaccine meningococcal serogroups were
      in the same range for MenACWY-CRM and JEV + PCECV + MenACWY-CRM. Rates of
      reporting of AEs were similar for JEV + PCECV and JEV + PCECV + MenACWY-CRM.
      CONCLUSIONS: MenACWY-CRM was administered with an inactivated adjuvanted JE and a
      purified chick embryo cell-culture rabies vaccine without compromising
      immunogenicity or safety of the individual vaccines. These data provide evidence
      that MenACWY-CRM could be effectively incorporated into travel vaccination
      programs. TRIAL NUMBER: NCT01466387.

PMID- 24873987
TI  - "A ce moment-la".

PMID- 24873989
TI  - Activation of a high-valent manganese-oxo complex by a nonmetallic Lewis acid.
AB  - The reaction of a manganese(V)-oxo porphyrinoid complex with the Lewis acid
      B(C6F5)3 leads to reversible stabilization of the valence tautomer Mn(IV)(O)(pi
      radical cation). The latter complex, in combination with B(C6F5)3, reacts with
      ArO-H substrates via formal hydrogen-atom transfer and exhibits dramatically
      increased reaction rates over the Mn(V)(O) starting material. 

PMID- 24873990
TI  - C2 compressive osteochondroma with transient neurologic symptoms in a pediatric
      patient.

PMID- 24873988
TI  - Sonic hedgehog and neurotrophin-3 increase oligodendrocyte numbers and
      myelination after spinal cord injury.
AB  - Spinal cord injury (SCI) results in loss of sensory and motor function below the
      level of injury and has limited available therapies. Multiple channel bridges
      have been investigated as a means to create a permissive environment for
      regeneration, with channels supporting axonal growth through the injury. Bridges
      support robust axon growth and myelination. Here, we investigated the cell types
      that myelinate axons in the bridges and whether over-expression of trophic
      factors can enhance myelination. Lentivirus encoding for neurotrophin-3 (NT3),
      sonic hedgehog (SHH) and the combination of these factors was delivered from
      bridges implanted into a lateral hemisection defect at T9/T10 in mice, and the
      response of endogenous progenitor cells within the spinal cord was investigated.
      Relative to control, the localized, sustained expression of these factors
      significantly increased growth of regenerating axons into the bridge and enhanced
      axon myelination 8 weeks after injury. SHH decreased the number of Sox2(+) cells
      and increased the number of Olig2(+) cells, whereas NT3 alone or in combination
      with SHH enhanced the numbers of GFAP(+) and Olig2(+) cells relative to control.
      For delivery of lentivirus encoding for either factor, we identified cells at
      various stages of differentiation along the oligodendrocyte lineage (e.g., O4(+),
      GalC(+)). Expression of NT3 enhanced myelination primarily by infiltrating
      Schwann cells, whereas SHH over-expression substantially increased myelination by
      oligodendrocytes. These studies further establish biomaterial-mediated gene
      delivery as a promising tool to direct activation and differentiation of
      endogenous progenitor cells for applications in regenerative medicine. 

PMID- 24873991
TI  - Examining the relationship between motor assessments and handwriting consistency
      in children with and without probable developmental coordination disorder.
AB  - Children with Developmental Coordination Disorder (DCD) often experience
      difficulties in handwriting. The current study examined the relationships between
      three motor assessments and the spatial and temporal consistency of handwriting.
      Twelve children with probable DCD and 29 children from 7 to 12 years who were
      typically developing wrote the lowercase letters "e" and "l" in cursive and
      printed forms repetitively on a digitizing tablet. Three behavioral assessments,
      including the Beery-Buktenica Developmental Test of Visual-Motor Integration
      (VMI), the Minnesota Handwriting Assessment (MHA) and the Movement Assessment
      Battery for Children (MABC), were administered. Children with probable DCD had
      low scores on the VMI, MABC and MHA and showed high temporal, not spatial,
      variability in the letter-writing task. Their MABC scores related to temporal
      consistency in all handwriting conditions, and the Legibility scores in their MHA
      correlated with temporal consistency in cursive "e" and printed "l". It appears
      that children with probable DCD have prominent difficulties on the temporal
      aspect of handwriting. While the MHA is a good product-oriented assessment for
      measuring handwriting deficits, the MABC shows promise as a good assessment for
      capturing the temporal process of handwriting in children with DCD.

PMID- 24873992
TI  - Differential expression of lipid peroxidation and total antioxidant status in
      Indian patients with cardiovascular and cerebrovascular disease.
AB  - Data from studies examining lipid peroxidation as a mechanism involved with
      hyperhomocysteinemia (HHcy)-induced vascular remodeling in patients with
      occlusive vascular disease have been contradictory. It has not yet been studied
      in Indians within the context of atherogenesis. Therefore, we measured the levels
      of homocysteine (Hcy), malondialdehyde (MDA) as a measure of lipid peroxides
      (LPOs), and total antioxidant status (TAS) in the serum of 167 patients with
      occlusive vascular disease [coronary artery disease (CAD) = 43; cerebrovascular
      disease (CVD) = 82; peripheral vascular disease (PVD) = 42]. Each of these groups
      was further divided into groups of individuals with or without HHcy. In the case
      of CAD and CVD, patients with HHcy had significantly higher LPOs than those
      without HHcy (p = 0.009, 0.001, respectively). TAS was significantly lower in CVD
      patients with HHcy than in those without (p = 0.014). In patients with CAD or
      CVD, Hcy directly correlated with LPOs (p = 0.002, 0.001, respectively). Lipid
      peroxidation is a significant mechanism in HHcy-induced vascular remodeling in
      CAD and CVD, but not in PVD, probably because it is not relevant in thrombosis
      (38 of 42 patients of PVD had deep-vein thrombosis). To explain the significantly
      lower TAS in CVD, we hypothesized that CVD patients present very early with grave
      symptoms, whereas CAD and PVD occur over a longer period of time. Therefore, when
      CVD presents, TAS is still overwhelmed by HHcy-induced oxidative stress. Hence,
      adjuvant therapy with antioxidants would benefit patients with CVD. 

PMID- 24873994
TI  - Rising incidence of celiac disease in the Netherlands; an analysis of temporal
      trends from 1995 to 2010.
AB  - OBJECTIVE: According to screening studies, celiac disease (CD) is prevalent in
      Western Europe. Actual prevalence tends to be much lower. The width of this
      actual gap is determined by the balance between disease symptoms and the "case
      finding" capabilities of the healthcare system. Therefore, we conducted a
      nationwide study to determine the temporal trends in the incidence in the
      Netherlands including a focus on demographic aspects. MATERIALS AND METHODS: We
      performed a nationwide search in the Dutch Pathology Registry (PALGA) to identify
      all biopsy-proven cases of CD in five different years between 1995 and 2010.
      Furthermore, demographic profiles and socioeconomic status (SES) of patients were
      studied. RESULTS: The overall incidence of CD increased from 2.72 (confidence
      interval [CI] 2.46-2.99) in 1995 to 6.65 (CI 6.27-7.06) per 100,000 inhabitants
      in 2010. No significant regional differences were noticed. In men, rates
      increased from 2.28 (CI 1.95-2.65) to 4.71 (CI 4.25-5.20) per 100,000 in 2010. In
      women, the increase was from 3.27 (CI 2.88-3.70) to 8.66 (CI 8.04-9.31) per
      100,000 in 2010. A trend toward leveling of incidence was observed from 2008 to
      2010. Patients diagnosed during childhood live in areas with a higher SES
      compared with patients diagnosed at adult age. CONCLUSION: The incidence of
      biopsy-proven CD in the Netherlands increased almost threefold between 1995 and
      2010. In areas with a higher SES, relatively more children were diagnosed.

PMID- 24873993
TI  - Can notochordal cells promote bone marrow stromal cell potential for nucleus
      pulposus enrichment? A simplified in vitro system.
AB  - Bone marrow stromal cells (BMSCs) have shown promising potential to stop
      intervertebral disc degeneration in several animal models. In order to restore a
      healthy state, though, this potential should be further stimulated. Notochordal
      cells (NCs), influential in disc development, have been shown to stimulate BMSC
      differentiation, but it is unclear how this effect will translate in an
      environment where resident disc cells (nucleus pulposus cells [NPCs]) could also
      influence BMSCs. The goal of this study was, therefore, to evaluate the effects
      of NCs on BMSCs when cocultured with NPCs, in a simplified 3D in vitro system.
      Bovine BMSCs and NPCs were mixed (Mix) and seeded into alginate beads. Using
      culture inserts, the Mix was then cocultured with porcine NCs (alginate beads)
      and compared to coculture with empty beads or porcine skin fibroblasts (SFs,
      alginate beads). NPCs alone were also cocultured with NCs, and BMSCs alone
      cultured under chondrogenic conditions. The effects of coculture conditions on
      cell viability, matrix production (proteoglycan and collagen), and gene
      expression of disc markers (aggrecan, type II collagen, and SOX9) were assessed
      after 4 weeks of culture. The NC phenotype and gene expression profile were also
      analyzed. Coculture with NCs did not significantly influence cell viability,
      proteoglycan production, or disc marker gene expression of the Mix. When compared
      to NPCs, the Mix produced the same amount of proteoglycan and displayed a higher
      expression of disc marker, indicating a stimulation of the BMSCs (and/or NPCs) in
      the Mix. Additionally, during the 4 weeks of culture, the NC phenotype changed
      drastically (morphology, gene expression profile). These results show that NCs
      might not be as stimulatory for BMSCs in an NPC-rich environment, as believed
      from individual cultures. This absence of effects could be explained by a mild
      stimulation provided by (de)differentiating NCs and the costimulation of BMSCs
      and NPCs by each other. 

PMID- 24873995
TI  - Cost-effectiveness of FDG-PET/CT for cytologically indeterminate thyroid nodules:
      a decision analytic approach.
AB  - CONTEXT: Patients with thyroid nodules of indeterminate cytology undergo
      diagnostic surgery according to current guidelines. In 75% of patients, the
      nodule is benign. In these patients, surgery was unnecessary and unbeneficial
      because complications may occur. Preoperative fluorodeoxyglucose-positron
      emission tomography/computed tomography (FDG-PET/CT) was found to have a very
      high negative predictive value (96%) and might therefore avoid futile surgery,
      complications, and costs. In the United States, two molecular tests of cytology
      material are routinely used for this purpose. OBJECTIVE: Five-year cost
      effectiveness for routine implementation of FDG-PET/CT was evaluated in adult
      patients with indeterminate fine-needle aspiration cytology and compared with
      surgery in all patients and both molecular tests. DESIGN: A Markov decision model
      was developed to synthesize the evidence on cost-effectiveness about the four
      alternative strategies. The model was probabilistically analyzed. One-way
      sensitivity analyses of deterministic input variables likely to influence outcome
      were performed. SETTING AND SUBJECTS: The model was representative for adult
      patients with cytologically indeterminate thyroid nodules. MAIN OUTCOME MEASURES:
      The discounted incremental net monetary benefit (iNMB), the efficiency decision
      rule containing outcomes as quality-adjusted life-years and (direct) medical
      cost, of implementation of FDG-PET/CT is displayed. RESULTS: Full implementation
      of FDG-PET/CT resulted in 40% surgery for benign nodules, compared with 75% in
      the conventional approach, without a difference in recurrence free and overall
      survival. The FDG-PET/CT modality is the more efficient technology, with a mean
      iNMB of ?3684 compared with surgery in all. Also, compared with a gene expression
      classifier test and a molecular marker panel, the mean iNMB of FDG-PET/CT was
      ?1030 and ?3851, respectively, and consequently the more efficient alternative.
      CONCLUSION: Full implementation of preoperative FDG-PET/CT in patients with
      indeterminate thyroid nodules could prevent up to 47% of current unnecessary
      surgery leading to lower costs and a modest increase of health-related quality of
      life. Compared with an approach with diagnostic surgery in all patients and both
      molecular tests, it is the least expensive alternative with similar effectiveness
      as the gene-expression classifier.

PMID- 24873996
TI  - Low-grade chronic inflammation in pregnant women with polycystic ovary syndrome:
      a prospective controlled clinical study.
AB  - CONTEXT: Polycystic ovary syndrome (PCOS) and pregnancy are conditions
      characterized by an increased low-grade chronic inflammation state. A higher
      incidence of pregnancy complications has been detected in pregnant PCOS women.
      OBJECTIVE: The objective of the study was to test the hypothesis that the low
      grade chronic inflammation state typical of PCOS patients persists during
      gestation and is exacerbated by pregnancy and contributes to the increased risk
      of obstetric/neonatal complications. DESIGN: This was a prospective controlled
      clinical study. SETTING: The study was conducted at the Academic Department of
      Obstetrics and Gynecology of the "Pugliese-Ciaccio" Hospital of Catanzaro
      (Catanzaro, Italy). PATIENTS: One hundred fifty pregnant PCOS women and 150 age-
      and body mass index-matched healthy pregnant controls participated in the study.
      INTERVENTIONS: INTERVENTIONS included serial clinical, biochemical, and
      ultrasonographic assessments before and throughout pregnancy. MAIN OUTCOME
      MEASURES: Serum levels of white blood cell count (WBC), C-reactive protein (CRP),
      and ferritin were measured. RESULTS: Pregnant women with PCOS had higher WBC,
      CRP, and ferritin levels at study entry and at all gestational ages than
      controls. Changes in serum WBC and ferritin levels were significantly higher in
      PCOS than in controls starting from the 12th week of gestation whereas those in
      CRP from the 20th week of gestation. By multivariable Cox proportional hazard
      analysis, in the PCOS group, a significant association with the risk of adverse
      obstetric/neonatal outcomes was found for WBC [hazard ratio (HR) 1.52, 95%
      confidence interval (CI) 1.31-1.64; P = .010], CRP (HR 1.19, 95% CI 1.06-1.34; P
      = .019), and ferritin levels (HR 1.12, 95% CI 1.03-1.26; P = .011). CONCLUSIONS:
      In PCOS patients, the low-grade chronic inflammation persists during gestation
      and is exacerbated by pregnancy, and it is associated with adverse pregnancy
      outcomes.

PMID- 24873997
TI  - Making sense of a multitude of (immoral) 'intoxicating stories'.

PMID- 24873998
TI  - Using media exposure to predict the initiation and persistence of youth alcohol
      use in Taiwan.
AB  - BACKGROUND: Youth consumption of alcohol is a major public health problem in
      Taiwan, yet little research has been conducted to examine the potential influence
      of exposure to alcohol advertising. The present study examined the prospective
      influence that exposure to alcohol advertising has on the initiation and
      persistence of youthful drinking in Taiwan. METHODS: A total of 2315 students
      from 26 high schools in Taipei, Taiwan were assessed in the 10th grade with
      follow-up conducted in the 11th grade. Self-administered questionnaires were
      collected in 2010 and 2011 to assess the patterns of change in youth alcohol
      drinking behaviors, media exposure to alcohol, and risk and protective factors.
      RESULTS: Of the 1712 non-drinking students in the 10th grade, 285 (16.6%) had
      initiated drinking by the 11th grade. Of the 590 drinkers in the 10th grade, 396
      (67.1%) were persistently drinking by the 11th grade. Multivariate analysis
      results indicated that when other potential confounders were accounted for,
      greater media exposure to alcohol advertising in the 10th grade was found to be
      significantly associated with the initiation of alcohol use and when combined
      with an increase in media exposure from grades 10 to 11, this was significantly
      associated with the persistence of alcohol use. CONCLUSION: Exposure to alcohol
      advertising in the media was associated with both the initiation and the
      persistence of alcohol use by youth.

PMID- 24873999
TI  - Advertising representation, treatment menu and economic circulation of substance
      misuse treatment centers in Iran: a rapid survey based on newspaper
      advertisements.
AB  - BACKGROUND: Daily newspapers are the main platform by which substance misuse
      treatment (SMT) centers in Iran advertise their services. However, these
      advertisements provide little information on treatment options or costs. The
      current research aimed to use advertisements to compile a schema of treatment
      services and to map the extent and nature of drug treatments offered. METHODS:
      During a four-week period (April to May) in 2009, the four most popular Persian
      newspapers printed in Tehran were reviewed. Across these publications 1704
      advertisements were posted by 66 SMT centers. Each center was then contacted by
      telephone to complete a structured interview about services offered and related
      costs. The advertisements were also decoded through a quantitative contextual
      analysis method. RESULTS: On average, each SMT center published 26 advertisements
      during the review period, costing 421 US$. In addition, advertisements included
      word signifiers in six main categories including centers' introduction (100%),
      treatment types (91%), treatment duration (68%), medicines (70%), treatment
      features (60%) and psychological facilities (52%). The three detoxification
      programs advertised were the rapid method (57% of clinics, 443.23 US$),
      buprenorphine (68%, 265 US$) and methadone (71%, 137 US$). More than 90% of the
      centers in Tehran were offering methadone maintenance (99 US$, per month).
      CONCLUSION: SMT services in the Iranian market ranged from abstinence to
      maintenance programs, with opiates as the main focus. This review of centers'
      advertisements provides an indirect but rapidly obtained picture of the drug
      misuse treatment network.

PMID- 24874000
TI  - Exploring the distribution of alcohol violation-types in North Carolina between
      2000 and 2011.
AB  - BACKGROUND: We used an exhaustive dataset of violations from the NC Alcohol Law
      Enforcement (ALE) agency to analyze 12 years of alcohol-related violations in NC.
      METHODS: Descriptive statistics were used to explore distribution and
      epidemiology of alcohol citations, including distributions by demographic
      factors, month, day of the week, and time of day. RESULTS: Approximately 47,065
      citations were issued by ALE during this time. The majority of the citations were
      issued to non-Hispanic (96%), white (89%), males (65%). The median age was 19
      years old (range 18-94). The months with the most citations were August through
      October and April. Citations issued on Thursday through Sunday accounted for
      approximately 87% of all citations issued. The most common types of violations
      were underage possession of beer/wine (55.5%), providing beer/wine to someone
      underage (13.6%), and underage possession of liquor (8.8%). CONCLUSION: This is
      the first study to examine the epidemiology of alcohol-related violations over a
      large geographical area. Other states, provinces, and/or countries can use these
      findings to exam if their distribution alcohol-related violations are comparable
      with this study, and explore associations between such data and alcohol use
      behaviors.

PMID- 24874001
TI  - The importance of evaluating the physicochemical and toxicological properties of
      a contaminant for remediating environments affected by chemical incidents.
AB  - In the event of a major chemical incident or accident, appropriate tools and
      technical guidance need to be available to ensure that a robust approach can be
      adopted for developing a remediation strategy. Remediation and restoration
      strategies implemented in the aftermath of a chemical incident are a particular
      concern for public health. As a result an innovative methodology has been
      developed to help design an effective recovery strategy in the aftermath of a
      chemical incident that has been developed; the UK Recovery Handbook for Chemical
      Incidents (UKRHCI). The handbook consists of a six-step decision framework and
      the use of decision trees specifically designed for three different environments:
      food production systems, inhabited areas and water environments. It also provides
      a compendium of evidence-based recovery options (techniques or methods for
      remediation) that should be selected in relation to their efficacy for removing
      contaminants from the environment. Selection of effective recovery options in
      this decision framework involves evaluating the physicochemical and toxicological
      properties of the chemical(s) involved. Thus, the chemical handbook includes a
      series of tables with relevant physicochemical and toxicological properties that
      should be assessed in function of the environment affected. It is essential that
      the physicochemical properties of a chemical are evaluated and interpreted
      correctly during the development of a remedial plan in the aftermath of a
      chemical incident to ensure an effective remedial response. This paper presents a
      general overview of the key physicochemical and toxicological properties of
      chemicals that should be evaluated when developing a recovery strategy.
      Information on how physicochemical properties have impacted on previous remedial
      responses reported in the literature is also discussed and a number of challenges
      for remediation are highlighted to include the need to develop novel approaches
      to remediate sites contaminated by mixtures of chemicals as well as methods for
      interpreting chemical reactions in different environmental matrices to include
      how climate change may affect the speciation and mobility of chemicals in the
      environment. 

PMID- 24874002
TI  - Factors influencing recovery and restoration following a chemical incident.
AB  - Chemicals are an important part of our society. A wide range of chemicals are
      discharged into the environment every day from residential, commercial and
      industrial sources. Many of these discharges do not pose a threat to public
      health or the environment. However, global events have shown that chemical
      incidents or accidents can have severe consequences on human health, the
      environment and society. It is important that appropriate tools and technical
      guidance are available to ensure that a robust and efficient approach to
      developing a remediation strategy is adopted. The purpose of remediation is to
      protect human health from future exposure and to return the affected area back to
      normal as soon as possible. There are a range of recovery options (techniques or
      methods for remediation) that are applicable to a broad range of chemicals and
      incidents. Recovery options should be evaluated according to their
      appropriateness and efficacy for removing contaminants from the environment;
      however economic drivers and social and political considerations often influence
      decision makers on which remedial actions are implemented during the recovery
      phase of a chemical incident. To date, there is limited information in the
      literature on remediation strategies and recovery options that have been
      implemented following a chemical incident, or how successful they have been.
      Additional factors that can affect the approach taken for recovery are not well
      assessed or understood by decision makers involved in the remediation and
      restoration of the environment following a chemical incident. The identification
      of this gap has led to the development of the UK Recovery Handbook for Chemical
      Incidents to provide a framework for choosing an effective recovery strategy. A
      compendium of practical evidence-based recovery options (techniques or methods
      for remediation) for inhabited areas, food production systems and water
      environments has also been developed and is included in the chemical handbook.
      This paper presents the key factors that should be considered when developing a
      recovery strategy with respect to how these may impact on its effectiveness. The
      paper also highlights the importance of these factors through an evaluation of
      recovery strategies implemented following real chemical incidents that have been
      reported in the literature. 

PMID- 24874004
TI  - Generation of brain cancer stem cells: the dark side of brain pericytes?

PMID- 24874003
TI  - Fragments of truth: T-cell targets of polyclonal immunoglobulins in autoimmune
      diseases.
AB  - The expanding therapeutic use of high-dose intravenous immunoglobulin (IVIg) in
      autoimmune diseases has raised important practical and conceptual issues over the
      last few years. These have prompted a number of research efforts aimed at
      characterizing aspects of the mechanism of action of current IVIg preparations,
      which might lead to the development of standardized, more cost-effective agents.
      Although polyclonal IgG in these preparations are mostly thought to act via
      direct interference with disease-specific, pathogenic autoantibodies, evidence
      from clinical and experimental work points to the involvement of crucial
      checkpoints upstream of self-reactive B-cell activation and autoantibody
      production. Reviewed herein are the results of the most recent studies
      documenting the crucial role of regulatory T cells (Treg) in the immunomodulatory
      activity of IVIg, and the molecular mechanisms mediating the effect of specific
      IgG fragments and glycoforms on Treg activity and the ensuing downregulation of T
      cell effector responses of different sign and magnitude. Further progress in this
      area of translational research may lead to the development of innovative
      strategies aimed at restoring tolerance in autoimmune diseases. 

PMID- 24874005
TI  - Relationship between sensitivity to visuotactile temporal discrepancy and the
      rubber hand illusion.
AB  - The rubber-hand illusion (RHI) is that the subject feels the visually presented
      tactile stimulation of an artificial (rubber) hand as their own tactile sensation
      and is caused by stimulating the rubber and real hands synchronously. Our
      previous study showed that the RHI was greatly reduced as the visual feedback
      delay of the tactile stimulation of the hand became longer. In the present study,
      we investigate the relationship between the attenuation of the RHI and the
      detection of the delay in two experiments: (1) an RHI experiment and (2) a
      visuotactile asynchrony detection experiment, in which the subjects underwent
      tactile stimulation of their hand and judged whether visual feedback was
      consistent with the touch sensation. In line with our previous study, the RHI was
      significantly reduced as the delay lengthened. Interestingly, proprioceptive
      drift declined linearly as the delay increased, while the delay detection rate
      was better fitted by a non-linear (logistic) function. The illusion score showed
      the intermittent pattern. We suggest that proprioceptive drift is relevant to the
      processing of the body schema, whereas the delay detection and the subjective
      feeling of the RHI are more related to the body image processing. 

PMID- 24874006
TI  - Effectiveness of a web-based solution-focused brief chat treatment for depressed
      adolescents and young adults: randomized controlled trial.
AB  - BACKGROUND: Up to 9% of young people suffer from depression. Unfortunately, many
      in need of help remain untreated. The Internet offers anonymous ways to help
      depressed youth, especially those who are reluctant to search for help because of
      fear of stigma. OBJECTIVE: Our goal was to evaluate the effectiveness of an
      individual chat treatment based on Solution-Focused Brief Therapy (SFBT) to young
      individuals aged 12-22 years with depressive symptoms by comparing it to a
      waiting list control group. METHODS: For this study, 263 young people with
      depressive symptoms were randomized to the Web-based SFBT intervention,
      PratenOnline, or to a waiting list control condition. The chat treatment was
      delivered by trained professionals. Groups were compared on depressive complaints
      as measured by the Center for Epidemiologic Studies Depression Scale (CES-D)
      after 9 weeks and 4.5 months. For the chat group only, changes in depressive
      symptoms at 7.5 months after baseline were explored. RESULTS: The experimental
      SFBT condition (n=131) showed significantly greater improvement than the waiting
      list condition (n=132) in depressive symptoms at 9 weeks and 4.5 months on the
      CES-D, with a small between group effect size at 9 weeks (d=0.18, 95% CI -0.10 to
      0.47) and a large effect size at 4.5 months (d=0.79, 95% CI 0.45-1.08). The
      percentage of participants showing a reliable and clinically significant change
      in depression was significantly larger for the SFBT intervention at 4.5 months
      only (28.2% vs 11.4% for the waiting list, P<.001, number needed to treat=6). At
      7.5 months, the SFBT group showed further improvements. However, results have to
      be considered carefully because of high attrition rates. CONCLUSIONS: The Web
      based SFBT chat intervention of PratenOnline was more effective than a waiting
      list control group in reducing depressive symptoms, and effects were larger at
      follow-up then at post-treatment. More studies are needed to find out if outcomes
      will be replicated, especially for those younger than 18 year old. TRIAL
      REGISTRATION: Netherlands Trial Register: NTR 1696;
      http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1696 (Archived by
      WebCite at http://www.webcitation.org/6DspeYWrJ).

PMID- 24874008
TI  - Effects of cadmium exposure on the gill proteome of Cottus gobio: modulatory
      effects of prior thermal acclimation.
AB  - Temperature and trace metals are common environmental stressors, and their
      importance is increasing due to global climate change and anthropogenic
      pollution. The aim of the present study was to investigate whether acclimation to
      elevated temperature affects the response of the European bullhead (Cottus gobio)
      to subsequent cadmium (Cd) exposure by using enzymatic and proteomic approaches.
      Fish acclimated to 15 (standard temperature), 18 or 21  degrees C for 28 days
      were exposed to 1mg Cd/L for 4 days at the respective acclimation temperature.
      First, exposure to Cd significantly decreased the activity of the lactate
      dehydrogenase (LDH) in gills of fish acclimated to 15 or 18  degrees C. However,
      an acclimation to 21  degrees C suppressed the inhibitory effect of Cd. Second,
      using a proteomic analysis by 2D-DIGE, we observed that thermal acclimation was
      the first parameter affecting the protein expression profile in gills of C.
      gobio, while subsequent Cd exposure seemed to attenuate this temperature effect.
      Moreover, our results showed opposite effects of these two environmental
      stressors at protein expression level. From the 52 protein spots displaying
      significant interaction effects of temperature and Cd exposure, a total of 28
      different proteins were identified using nano LC-MS/MS and the Peptide and
      Protein Prophet algorithms of Scaffold software. The identified differentially
      expressed proteins can be categorized into diverse functional classes, related to
      protein turnover, folding and chaperoning, metabolic process, ion transport, cell
      signaling and cytoskeleton. Within a same functional class, we further reported
      that several proteins displayed reverse responses following sequential exposure
      to heat and Cd. This work provides insights into the molecular pathways
      potentially involved in heat acclimation process and the interactive effects of
      temperature and Cd stress in ectothermic vertebrates.

PMID- 24874009
TI  - Cryo-TEM structural analysis of conjugated nonionic engineered-micelles.
AB  - Conjugated engineered-micelles, i.e. micelles that are composed of nonionic
      detergents and hydrophobic chelators and subsequently conjugated in the presence
      of divalent metal ions, have been shown to be remarkably suited to the task of
      membrane protein purification, maintaining these proteins in their native state.
      They also efficiently solubilize highly hydrophobic antibiotics. To date,
      however, the morphological changes induced in the initially spherical or
      ellipsoidal micelles by conjugation have not been explored. In this study, the
      very rapid sample-vitrification protocol of cryogenic transmission electron
      microscopy (cryo-TEM) has been used to capture structural transformations that
      engineered-micelles undergo immediately following conjugation with the
      [(bathophenanthroline)3:Fe(2+)] hydrophobic complex. We found that condensed
      thread-like aggregates are formed when the detergents used are: octyl beta-D
      glucopyranoside (OG), octyl beta-D-thioglucopyranoside (OTG) or pentaethylene
      glycol monododecyl ether (C12E5). However, with beta-D-maltoside (DM), n-dodecyl
      beta-D-maltoside (DDM) or beta-D-glucopyranoside (DDG), lamellar structures, some
      of which appear as stacked lamellae or multilamellar vesicles (MLV's), were
      observed. Such architectural changes occur under very mild conditions i.e. low
      detergent concentration, no temperature or pH alterations and without the
      presence of any precipitants such as PEG or ammonium sulfate.

PMID- 24874007
TI  - Natural dissolved organic matter mobilizes Cd but does not affect the Cd uptake
      by the green algae Pseudokirchneriella subcapitata (Korschikov) in resin buffered
      solutions.
AB  - Natural dissolved organic matter (DOM) can have contrasting effects on metal
      bioaccumulation in algae because of complexation reactions that reduce free metal
      ion concentrations and because of DOM adsorption to algal surfaces which promote
      metal adsorption. This study was set up to reveal the role of different natural
      DOM samples on cadmium (Cd) uptake by the green algae Pseudokirchneriella
      subcapitata (Korschikov). Six different DOM samples were collected from natural
      freshwater systems and isolated by reverse osmosis. In addition, one (13)C
      enriched DOM sample was isolated from soil to trace DOM adsorption to algae.
      Algae were exposed to standardized solutions with or without these DOM samples,
      each exposed at equal DOM concentrations and at equal non-toxic Cd(2+) activity
      (~4 nM) that was buffered with a resin. The DOM increased total dissolved Cd by
      factors 3-16 due to complexation reactions at equal Cd(2+) activity. In contrast,
      the Cd uptake was unaffected by DOM or increased maximally 1.6 fold ((13)C
      enriched DOM). The (13)C analysis revealed that maximally 6% of algal C was
      derived from DOM and that this can explain the small increase in biomass Cd. It
      is concluded that free Cd(2+) and not DOM-complexed Cd is the main bioavailable
      form of Cd when solution Cd(2+) is well buffered.

PMID- 24874010
TI  - Precipitation effects on microbial pollution in a river: lag structures and
      seasonal effect modification.
AB  - BACKGROUND: The river Gota Alv is a source of freshwater for 0.7 million swedes.
      The river is subject to contamination from sewer systems discharge and runoff
      from agricultural lands. Climate models projects an increase in precipitation and
      heavy rainfall in this region. This study aimed to determine how daily rainfall
      causes variation in indicators of pathogen loads, to increase knowledge of
      variations in river water quality and discuss implications for risk management.
      METHODS: Data covering 7 years of daily monitoring of river water turbidity and
      concentrations of E. coli, Clostridium and coliforms were obtained, and their
      short-term variations in relation with precipitation were analyzed with time
      series regression and non-linear distributed lag models. We studied how
      precipitation effects varied with season and compared different weather stations
      for predictive ability. RESULTS: Generally, the lowest raw water quality occurs 2
      days after rainfall, with poor raw water quality continuing for several more
      days. A rainfall event of >15 mm/24-h (local 95 percentile) was associated with a
      three-fold higher concentration of E. coli and 30% higher turbidity levels (lag
      2). Rainfall was associated with exponential increases in concentrations of
      indicator bacteria while the effect on turbidity attenuated with very heavy
      rainfall. Clear associations were also observed between consecutive days of wet
      weather and decreased water quality. The precipitation effect on increased levels
      of indicator bacteria was significant in all seasons. CONCLUSIONS: Rainfall
      elevates microbial risks year-round in this river and freshwater source and acts
      as the main driver of varying water quality. Heavy rainfall appears to be a
      better predictor of fecal pollution than water turbidity. An increase of wet
      weather and extreme events with climate change will lower river water quality
      even more, indicating greater challenges for drinking water producers, and
      suggesting better control of sources of pollution.

PMID- 24874011
TI  - Protection of neuronal cell death against diabetes-induced apoptosis by Fas
      blocker ZB4.
AB  - OBJECTIVE: To determine the role of apoptosis inhibition in the prevention of
      diabetic neuropathy using the antiFas cell surface death receptor (Fas)
      antagonistic monoclonal antibody ZB4. METHODS: This prospective study enrolled
      patients with type 2 diabetes with and without neuropathy and a group of healthy
      controls. The serum concentrations of Fas and Fas ligand (FasL) were measured in
      all study participants using an enzyme-linked immunosorbent assay. The ability of
      serum from study participants to induce apoptosis was evaluated in a human
      neuronal cell line using flow cytometry. RESULTS: A total of 28 healthy subjects
      and 57 patients with diabetes were enrolled in the study. Serum Fas
      concentrations were significantly increased in diabetes patients with and without
      neuropathy compared with the controls. Cells treated with the serum from diabetes
      patients with neuropathy had significantly higher rates of early apoptosis
      compared with cells treated with control serum. Monoclonal antibody ZB4 was able
      to block serum-induced apoptosis. CONCLUSIONS: Serum-induced apoptosis of a human
      neuronal cell line appeared to be mediated via Fas, which suggests that targeting
      and inhibiting Fas might offer a therapeutic target for diabetic neuropathy.

PMID- 24874012
TI  - Preliminary study on the mechanism of oridonin-induced apoptosis in human
      squamous cell oesophageal carcinoma cell line EC9706.
AB  - OBJECTIVE: To study the apoptosis-inducing effect of the Chinese medicine
      oridonin in the human oesophageal squamous cell carcinoma cell line EC9706, in
      vitro. METHODS: The effect of oridonin on cell proliferation was studied using
      the colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
      (MTT) assay. Effects on the cell cycle and apoptosis were studied by flow
      cytometry; effects on intracellular Ca(2+) concentration were studied by
      measuring the fluorescence intensity of a fluorescent Ca(2+) probe by laser
      scanning confocal microscopy. RESULTS: The EC9706 cell-proliferation rate
      decreased with time and oridonin concentration (10-40 umol/l). The number of
      cells in G0 and G1 phases increased significantly following exposure to oridonin
      for 48 and 72 h respectively, and oridonin was shown to be most effective at
      inducing apoptosis in EC9706 cells at 40 umol/l. Compared with the control group,
      all concentrations of oridonin tested (10-40 umol/l) significantly increased the
      Ca(2+) fluorescence intensity of EC9706 cells. CONCLUSIONS: Oridonin was shown to
      inhibit proliferation and induce apoptosis in the human oesophageal squamous cell
      carcinoma cell line EC9706, in vitro. These data provide preliminary experimental
      evidence for the anticancer effects of oridonin, which is as a traditional
      Chinese medicine used to treat various cancers, including oesophageal squamous
      cell carcinoma. Further studies are required to elucidate the mode of action.

PMID- 24874013
TI  - Finding novel molecular connections between developmental processes and disease.
AB  - Identifying molecular connections between developmental processes and disease can
      lead to new hypotheses about health risks at all stages of life. Here we
      introduce a new approach to identifying significant connections between gene sets
      and disease genes, and apply it to several gene sets related to human
      development. To overcome the limits of incomplete and imperfect information
      linking genes to disease, we pool genes within disease subtrees in the MeSH
      taxonomy, and we demonstrate that such pooling improves the power and accuracy of
      our approach. Significance is assessed through permutation. We created a web
      based visualization tool to facilitate multi-scale exploration of this large
      collection of significant connections (http://gda.cs.tufts.edu/development). High
      level analysis of the results reveals expected connections between tissue
      specific developmental processes and diseases linked to those tissues, and
      widespread connections to developmental disorders and cancers. Yet interesting
      new hypotheses may be derived from examining the unexpected connections. We
      highlight and discuss the implications of three such connections, linking
      dementia with bone development, polycystic ovary syndrome with cardiovascular
      development, and retinopathy of prematurity with lung development. Our results
      provide additional evidence that TGFB lays a key role in the early pathogenesis
      of polycystic ovary syndrome. Our evidence also suggests that the VEGF pathway
      and downstream NFKB signaling may explain the complex relationship between
      bronchopulmonary dysplasia and retinopathy of prematurity, and may form a bridge
      between two currently-competing hypotheses about the molecular origins of
      bronchopulmonary dysplasia. Further data exploration and similar queries about
      other gene sets may generate a variety of new information about the molecular
      relationships between additional diseases.

PMID- 24874016
TI  - T-cells play the classics with a different spin.
AB  - The immune system uses much of the classic machinery of cell biology, but in ways
      that put a different spin on organization and function. Striking recent examples
      include the demonstration of intraflagellar transport protein and hedgehog
      contributions to the immune synapse, even though immune cells lack a primary
      cilium that would be the typical setting for this machinery. In a second example,
      lymphocytes have their own subfamily of integrins, the beta2 subfamily, and only
      integrins in this family form a stable adhesion ring using freely mobile ligands,
      a key feature of the immunological synapse. Finally, we showed recently that T
      cells use endosomal sorting complexes required for transport (ESCRTs) at the
      plasma membrane to generate T-cell antigen receptor-enriched microvesicles. It is
      unusual for the ESCRT pathway to operate at the plasma membrane, but this may
      allow a novel form of cell-cell communication by providing a multivalent ligand
      for major histocompatibility complex-peptide complexes and perhaps other
      receptors on the partnering B-cell. Immune cells are thus an exciting system for
      novel cell biology even with classical pathways that have been studied
      extensively in other cell types. 

PMID- 24874018
TI  - Engineering homogeneous doping in single nanoparticle to enhance upconversion
      efficiency.
AB  - Upconversion nanoparticles (UCNPs) have shown considerable promises in many
      fields; however, their low upconversion efficiency is still the most serious
      limitation of their applications. Herein, we report for first time that the
      homogeneous doping approach based on the successive layer-by-layer method can
      greatly improve the efficiency of the UCNPs. The quantum yield as high as 0.89 +/
      0.05% is realized for the homogeneous doping NaGdF4:Yb,Er/NaYF4 UCNPs, which is
      nearly 2 times higher than that of the heterogeneous doping NaGdF4:Yb,Er/NaYF4
      UCNPs (0.47 +/- 0.05%). The influences of spatial distributions and local
      relative concentrations of the dopants on the optical properties of UCNPs were
      investigated in the single particle level. It was found that heterogeneous doping
      indeed existed during the spontaneous growth process of the nanoparticles. The
      heterogeneous doping property can further induce many negative effects on the
      optical properties of UCNPs, especially the luminescent efficiency. The spatial
      distributions and local relative concentrations of the dopants can be well
      controlled by the successive layer-by-layer homogeneous doping method on the
      monolayer level and homogeneously distributed in the single particle level.
      Furthermore, by using homogeneous doping NaGdF4:Yb,Tm as initial core, the
      multicolor emission intensity of NaGdF4:Yb,Tm/NaGdF4:A (A = Tb(3+), Eu(3+))
      core/shell nanoparticles can also exhibit 20%-30% improvement. We believe that
      such a homogeneous doping model can open the door to improve the upconversion
      optical properties by engineering the local distribution of the sensitizer,
      activator, host, etc., in a microcosmic and provide a track for engineering the
      high quality UCNPs with advanced nanostructure and optical properties. 

PMID- 24874015
TI  - Therapeutic targeting of Polo-like kinase-1 and Aurora kinases in T-cell acute
      lymphoblastic leukemia.
AB  - Polo-like kinases (PLKs) and Aurora kinases (AKs) act as key cell cycle
      regulators in healthy human cells. In cancer, these protein kinases are often
      overexpressed and dysregulated, thus contributing to uncontrolled cell
      proliferation and growth. T-cell acute lymphoblastic leukemia (T-ALL) is a
      heterogeneous malignancy arising in the thymus from T-cell progenitors. Primary
      chemoresistant and relapsed T-ALL patients have yet a poor outcome, therefore
      novel therapies, targeting signaling pathways important for leukemic cell
      proliferation, are required. Here, we demonstrate the potential therapeutic
      effects of BI6727, MK-5108, and GSK1070916, three selective inhibitors of PLK1,
      AK-A, and AK-B/C, respectively, in a panel of T-ALL cell lines and primary cells
      from T-ALL patients. The drugs were both cytostatic and cytotoxic to T-ALL cells
      by inducing G2/M-phase arrest and apoptosis. The drugs retained part of their pro
      apoptotic activity in the presence of MS-5 bone marrow stromal cells. Moreover,
      we document for the first time that BI6727 perturbed both the PI3K/Akt/mTORC2 and
      the MEK/ERK/mTORC1 signaling pathways, and that a combination of BI6727 with
      specific inhibitors of the aforementioned pathways (MK-2206, CCI-779) displayed
      significantly synergistic cytotoxic effects. Taken together, our findings
      indicate that PLK1 and AK inhibitors display the potential for being employed in
      innovative therapeutic strategies for improving T-ALL patient outcome.

PMID- 24874019
TI  - Interferometry with non-classical motional states of a Bose-Einstein condensate.
AB  - The Ramsey interferometer is a prime example of precise control at the quantum
      level. It is usually implemented using internal states of atoms, molecules or
      ions, for which powerful manipulation procedures are now available. Whether it is
      possible to control external degrees of freedom of more complex, interacting many
      body systems at this level remained an open question. Here we demonstrate a two
      pulse Ramsey-type interferometer for non-classical motional states of a Bose
      Einstein condensate in an anharmonic trap. The control sequences used to
      manipulate the condensate wavefunction are obtained from optimal control theory
      and are directly optimized to maximize the interferometric contrast. They permit
      a fast manipulation of the atomic ensemble compared to the intrinsic decay
      processes and many-body dephasing effects. This allows us to reach an
      interferometric contrast of 92% in the experimental implementation. 

PMID- 24874017
TI  - TRPV2 is critical for the maintenance of cardiac structure and function in mice.
AB  - The heart has a dynamic compensatory mechanism for haemodynamic stress. However,
      the molecular details of how mechanical forces are transduced in the heart are
      unclear. Here we show that the transient receptor potential, vanilloid family
      type 2 (TRPV2) cation channel is critical for the maintenance of cardiac
      structure and function. Within 4 days of eliminating TRPV2 from hearts of the
      adult mice, cardiac function declines severely, with disorganization of the
      intercalated discs that support mechanical coupling with neighbouring myocytes
      and myocardial conduction defects. After 9 days, cell shortening and Ca(2+)
      handling by single myocytes are impaired in TRPV2-deficient hearts. TRPV2
      deficient neonatal cardiomyocytes form no intercalated discs and show no
      extracellular Ca(2+)-dependent intracellular Ca(2+) increase and insulin-like
      growth factor (IGF-1) secretion in response to stretch stimulation. We further
      demonstrate that IGF-1 receptor/PI3K/Akt pathway signalling is significantly
      downregulated in TRPV2-deficient hearts, and that IGF-1 administration partially
      prevents chamber dilation and impairment in cardiac pump function in these
      hearts. Our results improve our understanding of the molecular processes
      underlying the maintenance of cardiac structure and function. 

PMID- 24874020
TI  - Treatment of separation, generalized, and social anxiety disorders in youths.
AB  - Separation, generalized, and social anxiety disorders are common and impairing
      for children and adolescents. Childhood-onset anxiety disorders frequently
      persist into adulthood and place youths at risk for future psychiatric disorders,
      including mood and substance use disorders. Comorbidity is common in childhood
      anxiety disorders, and studies increasingly take this into account when assessing
      potential treatments. Existing studies support a number of pharmacological and
      psychotherapeutic treatments for childhood anxiety disorders. The strongest
      evidence supports use of selective serotonin reuptake inhibitors (SSRIs) and
      cognitive-behavioral therapy (CBT). Combination treatment with SSRIs and CBT has
      been found to be more effective than either treatment alone. Early detection and
      treatment of childhood anxiety disorders can prevent substantial impairment over
      the course of a child's development and accumulation of functional disability.
      Early treatment also may prevent later development of adult psychiatric illness.
      The authors review the treatment literature and present the case of an adolescent
      who is brought in for evaluation after years of untreated anxiety. 

PMID- 24874022
TI  - Atomic-scale configurations of synchroshear-induced deformation twins in the
      ionic MnS crystal.
AB  - Deformation twinning was thought as impossible in ionic compounds with rock-salt
      structure due to the charge effect on {111} planes. Here we report the presence
      and formation mechanism of deformation {111} twins in the rock-salt manganese
      sulphide (MnS) inclusions embedded in a hot-rolled stainless steel. Based on the
      atomic-scale mapping under aberration-corrected scanning transmission electron
      microscopy, a dislocation-based mechanism involved two synchronized shear on
      adjacent atomic layers is proposed to describe the dislocation glide and
      consequently twinning formation. First-principles calculations of the energy
      barriers for twinning formation in MnS and comparing with that of PbS and MgO
      indicate the distinct dislocation glide scheme and deformation behaviors for the
      rock-salt compounds with different ionicities. This study may improve our
      understanding of the deformation mechanisms of rock-salt crystals and other ionic
      compounds. 

PMID- 24874021
TI  - Molecular programme of senescence in dry and fleshy fruits.
AB  - Fruits of angiosperms can be divided into dry and fleshy fruits, depending on
      their dispersal strategies. Despite their apparently different developmental
      programmes, researchers have attempted to compare dry and fleshy fruits to
      establish analogies of the distinct biochemical and physiological processes that
      occur. But what are the common and specific phenomena in both biological
      strategies? Is valve dehiscence and senescence of dry fruits comparable to final
      ripening of fleshy fruits, when seeds become mature and fruits are competent for
      seed dispersal, or to over-ripening when advanced senescence occurs? We briefly
      review current knowledge on dry and fleshy fruit development, which has been
      extensively reported recently, and is the topic of this special issue. We compare
      the processes taking place in Arabidopsis (dry) and tomato (fleshy) fruit during
      final development steps using transcriptome data to establish possible analogies.
      Interestingly, the transcriptomic programme of Arabidopsis silique shares little
      similarity in gene number to tomato fruit ripening or over-ripening. In contrast,
      the biological processes carried out by these common genes from ripening and over
      ripening programmes are similar, as most biological processes are shared during
      both programmes. On the other hand, several biological terms are specific of
      Arabidopsis and tomato ripening, including senescence, but little or no specific
      processes occur during Arabidopsis and tomato over-ripening. These suggest a
      closer analogy between silique senescence and ripening than over-ripening, but a
      major common biological programme between Arabidopsis silique senescence and the
      last steps of tomato development, irrespective of its distinction between
      ripening and over-ripening. 

PMID- 24874023
TI  - Systemic lidocaine in surgical procedures: effects beyond sodium channel
      blockade.
AB  - PURPOSE OF REVIEW: This review presents current data on the systemic
      administration of lidocaine. The focus is on studies in the perioperative
      setting. In addition, there is a brief look at experimental data on the effect of
      lidocaine at the molecular level. RECENT FINDINGS: Several recent randomized
      prospective studies have reported lower postoperative pain values and less opioid
      administration in lidocaine groups in comparison with control groups receiving
      NaCl. However, there are conflicting data particularly in relation to patients
      undergoing nonabdominal surgery and on effects on postoperative resumption of
      bowel motility and hospital discharge times. Unfortunately, hardly any studies
      have investigated the effects of systemic lidocaine in comparison with epidural
      anesthesia. At the molecular level, a number of receptors and signal transduction
      cascades have been identified. SUMMARY: Positive effects on postoperative pain,
      as well as on bowel motility and hospital discharge time, have regularly been
      observed. However, contradictory findings have also been published. As almost all
      of the studies only include very small patient numbers, large multicenter
      investigations are needed.

PMID- 24874024
TI  - Hydrodynamic and nonhydrodynamic contributions to the bimolecular collision rates
      of solute molecules in supercooled bulk water.
AB  - Bimolecular collision rate constants of a model solute are measured in water at T
      = 259-303 K, a range encompassing both normal and supercooled water. A stable,
      spherical nitroxide spin probe, perdeuterated 2,2,6,6-tetramethyl-4-oxopiperidine
      1-oxyl, is studied using electron paramagnetic resonance spectroscopy (EPR),
      taking advantage of the fact that the rotational correlation time, tau(R), the
      mean time between successive spin exchanges within a cage, tau(RE), and the long
      time-averaged spin exchange rate constants, K(ex), of the same solute molecule
      may be measured independently. Thus, long- and short-time translational diffusion
      behavior may be inferred from K(ex) and tau(RE), respectively. In order to
      measure K(ex), the effects of dipole-dipole interactions (DD) on the EPR spectra
      must be separated, yielding as a bonus the DD broadening rate constants that are
      related to the dephasing rate constant due to DD, W(dd). We find that both K(ex)
      and W(dd) behave hydrodynamically; that is to say they vary monotonically with
      T/eta or eta/T, respectively, where eta is the shear viscosity, as predicted by
      the Stokes-Einstein equation. The same is true of the self-diffusion of water. In
      contrast, tau(RE) does not follow hydrodynamic behavior, varying rather as a
      linear function of the density reaching a maximum at 276 +/- 2 K near where water
      displays a maximum density.

PMID- 24874025
TI  - Finite element analysis of lumbosacral reconstruction after partial sacrectomy.
AB  - BACKGROUND: The biomechanical property of MGT for patients who underwent partial
      sacrectomy is not well documented, so this study aimed to investigate
      biomechanical property of lumbosacral reconstruction after partial sacrectomy.
      MATERIAL AND METHODS: Three 3-dimensional finite element models of lumbosacral
      region were established: 1) an intact model (INT), 2) a defective model in which
      partial sacrectomy was performed cephalad to S1 foramina (DEF), and 3) a
      reconstructed model (REC). RESULTS: Displacements of anchor point on L3 vertebrae
      in INT, DEF, and REC model were 6.63 mm, 10.62 mm, 4.29 mm (titanium), and 3.86mm
      (stainless steel), respectively. Stress distribution of the instrument in REC
      model showed excessive concentration on the caudal spinal rod, which may cause
      rod failure between spine and ilia. Maximum von Mise stress of the stainless
      steel instrument was higher than titanium instruments, and values of stress of
      the anchor point around the sacroiliac joint in the REC model were 26.4 MPa with
      titanium instruments and 23.9MPa with stainless steel instruments. CONCLUSIONS:
      Lumbosacral reconstruction can significantly increase stiffness of the
      spinopelvis of patients who underwent partial sacrectomy. However, the rod
      between L5 and ilia is the weakest region of all instruments. Stainless steel
      instruments have higher risk of rod failure and are less suitable for lumboiliac
      arthrodesis than titanium instruments.

PMID- 24874026
TI  - Social and Gendered Readings of Illness Narratives.
AB  - This essay recognizes that the interactions that define medical care are
      problematic and that narrative is invoked to overcome these strains. Being
      grounded in science, medicine, too, might be influenced by a particular world
      view that arose in the natural philosophy of the Scientific Revolution. If
      narrative responds to this sort of medicine, it may retain traces of this
      mindset. A feminist approach responds to this viewpoint and may used beneficially
      to analyze both the story of medicine and the stories within medicine. Tensions
      discussed from this perspective are those between sickness and health and those
      between patient and provider; also questioned are suitable form(s) of narrative
      and whose narratives are valued. Suggestions for broadening narrative to address
      these issues include letting the body speak for itself, overcoming the power
      differential in the patient/provider interaction and using standpoints to foster
      a more equal and just medical system. 

PMID- 24874027
TI  - From static to dynamic 1.5T MRI-linac prototype: impact of gantry position
      related magnetic field variation on image fidelity.
AB  - Recently, the MRI-linac prototype at UMC Utrecht was upgraded with a ring-based
      gantry, where all linac components are mounted on a ring around the MR scanner.
      Although adaptations have been made to both linac and MR magnets in order to
      account for mutual magnetic interference, interference problems cannot be ruled
      out completely. Therefore, in this paper the impact of gantry position dependent
      magnetic field inhomogeneity variation on the geometrical accuracy of acquired MR
      images is quantified. Magnetic field maps were acquired in a large field of view
      for static gantry positions in shimmed and un-shimmed conditions. Reproducibility
      of the shim settings was assessed. From the fieldmaps, a minimum gradient
      strength needed to acquire images with geometric distortions of, at most, 1 mm
      was derived. Moreover, imaging during gantry rotation was performed for a range
      of imaging parameters and rotation speeds. From the measurements we conclude that
      images with good geometric fidelity can be obtained for all static gantry
      positions, provided that shimming is performed for each new gantry position. This
      indicates that the present prototype is suitable for static IMRT scenarios. Shim
      settings are highly reproducible, suggesting that shimming via look-up tables is
      feasible. Finally, imaging during gantry rotation may produce severely distorted
      images at present and is likely to require advanced compensation methods such as
      dynamic shimming or higher order reconstruction. 

PMID- 24874028
TI  - Contemporary insights and novel treatment approaches to central sleep apnea
      syndrome in heart failure.
AB  - OPINION STATEMENT: Central sleep apnea (CSA) is a common and under-diagnosed
      condition commonly associated with Cheyne-Stokes respiration. It is particularly
      prevalent in the heart failure population affecting up to 40 % of all patients
      with heart failure. The pathophysiology associated with CSA is based on the
      underlying effects of hypoventilation and hyperventilation, with neurologic
      dysregulation of respiratory control as the primary defect. However, therapeutic
      options are limited because of the prevailing perception that CSA is a
      consequence, rather than cause of morbidity and mortality. At present, the main
      focus remains treating the underlying problem (ie, intensifying heart failure
      therapeutics, decongestion), whereas additional suggestions of using
      acetazolamide, progesterone, nocturnal oxygen, and theophylline have not been
      validated with contemporary clinical trials. Positive pressure ventilation is
      currently the primary recommendation for all patients with sleep-disordered
      breathing (CSA included), and in some patients may effectively reduce the apnea
      hypopnea index. However, significant research is ongoing to determine how to
      treat this complex patient population.

PMID- 24874029
TI  - The search for early markers of AD: hippocampal atrophy and memory deficits.

PMID- 24874030
TI  - 13C NMR analysis of 3,6-dihydro-2H-pyrans: assignment of remote stereochemistry
      using axial shielding effects.
AB  - The rational analysis of (13)C NMR axial shielding effects has enabled the
      assignment of remote relative stereochemistry in 3,6-oxygen-substituted 3,6
      dihydro-2H-pyrans. Comparison of the (13)C NMR shifts of equivalent centers in
      cis- and trans-substituted 3,6-dihydro-2H-pyrans allows the relative
      configuration at the C3 and C6 positions to be defined in diastereoisomeric
      mixtures. Density functional calculations were used to validate this method and
      assess the conformational bias present in the ring system. Ultimately, the
      coupling of computational chemistry with this (13)C NMR-based method provided a
      reliable and convenient method for stereochemical assignment of a single
      diastereomer. This approach provides a facile and complementary alternative to
      the practices previously employed for determining the relative configuration in
      3,6-dihydro-2H-pyrans. 

PMID- 24874033
TI  - Properties of gamma-glutamyltransferase in developing rat brain.
AB  - The activity and properties of brain gamma-glutamyltransferase (EC 2.3,2.2) were
      studied in 7-, 14-and 90-day-old rats. The enzyme activity was highest in the
      pons-medulla and lowest in the cerebellum in each age group. The activity of
      glycylglycine, 10 protein amino acids, GABA and taurine as acceptor of the gamma
      glutamyl group was studied with 7-day-old and adult rats. The best acceptors were
      glycylglycine, lysine and methionine and the poorest taurine, valine and
      isoleucine. The relative acceptor activity of lysine changed most during
      development. Km for the gamma-glutamyl donor, gamma-glutamyl-p-nitroanilide, with
      glycylglycine was about 3 mM in all experimental groups. It did not change during
      development but V increased about fivefold in all brain areas studied. A mixture
      of serine and borate strongly inhibited gamma-glutamyltransferase in each age
      group. Potassium and magnesium ions had no measurable effect on the enzyme
      activity but sodium ions were stimulatory. 

PMID- 24874031
TI  - Multidetector computed tomography of iliac vein variation: prevalence and
      classification.
AB  - PURPOSE: To determine the prevalence of iliac venous variations and to classify
      the variations using multidetector computed tomography (MDCT). MATERIALS AND
      METHODS: MDCT images of 2,488 patients were retrospectively reviewed. Iliac
      venous variations were documented and classified with regard to internal iliac
      vein (IIV) drainage patterns, the presence of interiliac communicating veins and
      inferior vena cava (IVC) anomalies associated with iliac venous variations. The
      variation prevalence rates were analyzed and calculated. RESULTS: The incidence
      of iliac venous variations was 20.9%, and these were classified into eight types:
      normal, 79.1% (type 1); high joining of the IIV to the ipsilateral external iliac
      vein, 8.7% (type 2); the IIV joining to the contralateral common iliac vein
      (CIV), 2.3% (type 3); IIVs forming a common trunk, 0.9% (type 4); communicating
      vein from the IIV to the contralateral CIV or IIV, 7.8% (type 5); double IVC with
      or without a connecting vein, 0.9% (type 6); left IVC, 0.1% (type 7); and
      fenestration of the CIV, 0.4% (type 8). There were subtypes which varied
      according to right- or left-side variation and the status of smaller connecting
      veins. No statistical difference in the prevalence rate was found between men and
      women (p = 0.365). CONCLUSIONS: Iliac venous variations are frequently seen on
      MDCT and can be classified into 8 types.

PMID- 24874032
TI  - Evaluation of the relationship between the maxillary posterior teeth and the
      sinus floor using cone-beam computed tomography.
AB  - AIM: The aim of this study was to evaluate the relationship between each root of
      maxillary premolars and molars and the maxillary sinus floor according to sex,
      sinus position, and age by decade in a Turkish population by using cone-beam
      computed tomography (CBCT) scanning. METHODOLOGY: We evaluated a database of
      5,166 (2,680 maxillary premolars and 2,486 maxillary molars) CBCT scans obtained
      from 849 patients. The vertical relationship between each root of the molar and
      premolar teeth to the sinus floor was classified into three types: type 1, the
      roots penetrated into the sinus floor; type 2, the roots contacted the sinus
      floor; and type 3, the roots extended below the sinus floor. RESULTS: The results
      of the classification of each root in relationship to the sinus floor were as
      follows: type 3 occurred most frequently in the first (92.4 %) and second (71.6
      %) premolar teeth, type 1 (34.2 %) occurred most frequently in the palatinal
      roots of the first molar teeth, type 3 occurred most frequently in the
      mesiobuccal (39.9 %) and distobuccal (39.7 %) roots of the first molar teeth, and
      type 2 (36.7 %) occurred most frequently in the mesiobuccal roots of the second
      molar teeth. No significant differences were found between the left and right
      sides, but several differences were found between males and females. The
      relationship between the posterior teeth and the sinus floor differed according
      to the age decade interval (p < 0.05). CONCLUSIONS: The maxillary first premolars
      have no relationship with the maxillary sinus floor, but the maxillary second
      molars are closer to the sinus floor. Also the second decade and males were most
      susceptible to undesirable results.

PMID- 24874034
TI  - Brain malformations in prenatal mice following acute maternal ethanol
      administration.
AB  - Acute maternal ethanol administration (two i.p. injections of 2.9 g ethanol/kg
      maternal body wt) to C57B1/6J mice during gastrulation stages of embryogenesis
      (gestational day 7) induces a spectrum of brain and facial malformations
      characteristic of those seen in the human Fetal Alcohol Syndrome. Scanning
      electron microscopic and light microscopic analyses of the brains of embryos of
      gestational days 11-14 demonstrate ventro-medial forebrain deficiencies of
      varying degrees of severity in affected specimens. Even at the mild end of the
      spectrum, reductions in the size of the septal nuclei and the shape of the third
      ventricle are observed. As the severity of the effect increases, the septal
      nuclei disappear altogether, resulting in midline fusion of the corpora striata
      (basal ganglia). In such cases, the third ventricle is totally absent anteriorly
      (preoptic area) and significantly narrowed at more posterior levels, adjacent to
      the ventromedial nuclei. In addition, the hippocampal primordium is absent at
      levels which include the corpora striata, and septation of the cerebral cortex is
      incomplete. More posteriorly, at the level of the posterior commissure, the
      hippocampal primordium is present, but greatly reduced in size, and the entire
      brain is distinctly narrower in width. Still further posteriorly, at levels of
      the metencephalon which include the tectum and cerebellar plate, the cerebral
      aqueduct is significantly expanded, fusion of midline (raphe) structures is
      incomplete and the cerebellar plate does not extend as far medially as it does
      normally. Interestingly, these abnormalities are analogous to those observed in
      the holoprosencephaly series of malformations. The results of the present study
      support our hypothesis that severe forms of the Fetal Alcohol Syndrome mimic
      certain aspects of the holoprosencephaly spectrum, and indicate that special
      attention should be paid to possible deficiencies in the septal nuclei and basal
      ganglia of children born to women who abuse alcohol. The fact that gross brain
      malformations can be induced in this animal model at a time corresponding to the
      third week of human gestation (a time when most women remain unaware of
      pregnancy) is of significance in terms of the possible prevention of alcohol
      induced birth defects and mental deficiency in man. 

PMID- 24874036
TI  - Long-term reduction in spontaneous alternations after early exposure to
      phenobarbital.
AB  - Spontaneous alternation behavior is related to the integrity of the hippocampus.
      Our earlier studies demonstrated hippocampal deficits after early phenobarbital
      (PhB) exposure. In the present study, we examined spontaneous alternation of mice
      who had been exposed to PhB prenatally or neonatally. Prenatal PhB was
      administered transplacentally: pregnant females were fed 3 g PhB/kg milled food
      on gestation days 9-18. Neonates were treated directly with daily injections of
      50 mg PhB/kg on postnatal days 2-22. The animals were tested for spontaneous
      alternation in a T maze at the ages of 22, 28, 35 and 42 days. The test was
      conducted at each age for two consecutive days. A maximum of four alternations
      were allowed on the first day, and one alternation on the second day. Animals
      treated neonatally had reductions in alternation from the control group for every
      age group. Looking at the mean of the four trials on the first day there was a
      reduction of 35% at age 22 (P < 0.001), 8% at age 28, 21% at age 35 (P < 0.05)
      and 36% at age 42 (P < 0.02). On the second day the respective reductions were
      32, 19, 24 and 36% (P < 0.05). The differences in alternation between animals
      treated with PhB prenatally and the control group were too small to reach
      statistical significance. Subsequently a more sensitive test, delayed spontaneous
      alternation (30 s), was applied to an additional group of animals at age 42 which
      had been prenatally exposed to PhB: 31% reduction from the control group was
      found on day 1 (P < 0.001), and 34% on day 2 (P < 0.02). The greater differences
      after neonatal as opposed to prenatal administration could be related to the more
      extensive hippocampal damage that was found in adults after neonatal treatment. 

PMID- 24874035
TI  - Synthesis of plasma proteins by rat fetal brain and choroid plexus.
AB  - Several plasma proteins have previously been demonstrated to be within cells
      (presumed neurons) in the developing brain of various species. The possibility
      that the plasma proteins alpha-fetoprotein (AFP) albumin and transferrin may be
      synthesized by developing brain and choroid plexus has been investigated in fetal
      rats of 18 to 22 days gestation. Samples of these tissues and of liver were
      incubated in Krebs solution containing [(3)H]leucine at 37 degrees C for 1 h.
      Radioactively labelled AFP, albumin and transferrin were extracted and separated
      by immunoprecipitation. Incorporation of [(3)H]leucine into the plasma proteins
      was demonstrated in both fetal brain and choroid plexus. Incorporation was
      completely blocked by cycloheximide. It is concluded that fetal brain and choroid
      plexus synthesize AFP, albumin and transferrin and that secretion of these
      proteins by developing brain and choroid plexus cells probably contributes to the
      high concentration of plasma proteins in fetal csf. 

PMID- 24874037
TI  - The effect of culture on the neuronotrophic activity of avian smooth muscle.
AB  - The expansor secundariorum is a smooth muscle of the chicken wing which receives
      a dense noradrenergic innervation and contains high concentrations of trophic
      activity for sympathetic neurons. Expansor cells were dissociated in trypsin and
      grown to confluency in standard nutrient medium. Medium that had been conditioned
      by expansor cells contained trophic activity for chick sympathetic nerves which
      differed from the activity which is found within the muscle prior to culture, in
      that it was effective on a different neuronal subpopulation. Furthermore, unlike
      the factor(s) found in vivo, the trophic activity of the conditioned medium was
      not enhanced by NGF and could be partially inhibited by mouse NGF antibodies.
      Both the production of total trophic activity in the conditioned medium and the
      activity which differed from that in the muscle extract, increased rapidly and to
      the same extent between 24 and 48 h culture. Greater concentrations of trophic
      activity were present in medium conditioned by smooth muscle cells than by skin
      cells. The conditioned medium was able to support more neurons from 11 and 18 day
      incubated embryos than a saturating dose of NGF. Neither this effect nor the
      additive effect of conditioned medium with expansor muscle extract could be
      attributed to the presence of neurite promoting factors. We conclude that the
      cultured muscle produces neuronotrophic activity that is similar to the activity
      found in denervated but not innervated muscle. 

PMID- 24874038
TI  - Viability of locus coeruleus cultures in the fourth ventricle of the adult rat.
AB  - Both tyrosine hydroxylase and dopamine-beta-hydroxylase immunocytochemistry
      indicated the survival of catecholamine neurons and processes in 7-day-old
      organotype cultures of the locus coeruleus. Cultures of this age were
      transplanted in the 4th ventricle of adult rats via the cisterna magna. Two
      months after transplantation microscopic observations revealed that the
      transplant developed with a defined neural organization. Following tyrosine
      hydroxylase immunocytochemistry, immunoreactive cells were identified within the
      transplants. These results indicate that organotype cultures of the locus
      coeruleus survive within the 4th ventricle of adult rats. 

PMID- 24874039
TI  - GABA influences the ultrastructure composition of cerebellar granule cells during
      development in culture.
AB  - The influence of GABA on cerebellar granule cells in culture was followed
      morphometrically during in vitro development by growing the cells in the absence
      or presence of 50 MUM GABA. The presence of GABA in the culture media increased
      the number of neurite-extending cells by 50% after 7 days in culture. At the
      ultrastructural level GABA treatment led to an increased density of neurotubules,
      rough endoplasmic reticulum, Golgi apparatus, coated vesicles and other vesicles,
      whereas structures such as mitochondria and smooth endoplasmic reticulum were not
      affected by GABA. The density of free ribosomes showed a more pronounced tendency
      to decrease as a function of the culture period (1-7 days) when the cells were
      grown in the presence of GABA as compared to control cultures. The results
      strongly indicate that GABA in addition to being an important neurotransmitter
      serves as a trophic factor in the development of at least certain types of
      neurons. 

PMID- 24874040
TI  - Some properties of uridine-5'-diphospho-N-acetylgalactosamine:Hematoside N
      acetylgalactosaminyltransferase at early and late stages of embryonic development
      of chicken retina.
AB  - Some properties of the uridine-5'-diphospho-N-acetylgalactosamine:hematoside N
      acetylgalactosaminyltransferase were studied in retina tissue from chick embryos
      at 7 and 14 days of development. The Vmax was about 6-fold higher in retinas from
      14 day embryos than in retinas from 7 day embryos. No differences were found
      either in the apparent Michaelis constant for both donor nucleotide and acceptor
      glycolipid, or in the optimal detergent concentration, or in the stability upon
      storage at -14 degrees C or heating at 50 degrees C. Mixtures of homogenates of
      retinas from 7 day and from 14 day embryos gave the activity values expected for
      samples free of effectors diffusible and in excess. From experiments of partial
      delipidation of retina homogenates and reconstitution with lipid from retina
      homogenates from one or the other age, no indications were found that the
      activity was modulated by developmental changes in the lipid environment of the
      enzyme. Taken together, the results suggest that the increase of activity during
      development was not due to qualitative changes in the catalytic characteristics
      of the enzyme. 

PMID- 24874041
TI  - Monosialoganglioside internal ester stimulates the dopaminergic reinnervation of
      the striatum after unilateral hemitransection in rat.
AB  - The effects of the administration of GM1 monosialoganglioside internal ester,
      AGF2, on the dopaminergic reinnervation of the striatum in rats with unilateral
      hemitransection has been studied. AGF2 increases the apparent Vmax and the
      density of tyrosine-hydroxylase-positive nerve terminals in the striatum of the
      lesioned side, without modification of the tyrosine-hydroxylase activity in the
      unlesioned side. AGF2, at lower doses, is more active than its parent natural
      molecule GM1. AGF2 has a larger half-life and a higher distribution volume than
      GM1, and undergoes a slow hydrolysis in the serum releasing the original natural
      compound GM1. Mannitol and dexamethazone, often used to prevent swelling of the
      brain after injury, or isoaxonine, proposed to stimulate neurite growth are
      unable to reproduce the effects of AGF2 on the recovery of striatal tyrosine
      hydroxylase activity after hemitransection. The data are compatible with the view
      that AGF2, through its conversion into GM1, facilitates the collateral sprouting
      of the nigro-striatal dopaminergic neurons. 

PMID- 24874042
TI  - Effects of triiodothyronine (T3) on the development of rat cerebellar cells in
      culture.
AB  - To determine whether or not the effects of thyroxine on the cells of the external
      granular layer of rat cerebellum are direct or indirect, Purkinje cell-free
      dissociated cell cultures from 5-day-old rat cerebellum in serum-free medium were
      treated with triiodothyronine (T3) at concentrations of 20-3000 ng/ml. Cultures
      were assayed for uptake and synthesis of gamma-aminobutyric acid (GABA) after 3
      weeks, and for thymidine incorporation at 1, 2, 3 and 4 days. Specific (per mg
      protein) activity of glutamic acid decarboxylase and of GABA uptake into neurons
      was reduced by the more physiologic (50 or 500 ng/ml) concentrations of T3,
      probably due to a non-neuronal increase in overall protein synthesis, since the
      total per culture values seem unaffected by hormone. Thymidine uptake was
      significantly increased only at the highest (unphysiologic) concentration of T3
      on the second day after treatment. None of the label appeared to be in the nuclei
      of the neuronal cells at any of the times and concentrations tested. These
      results are consistent with the hypothesis that T3 does not have a direct effect
      on the proliferation of neurons derived from the external granular layer,
      although it does seem to affect some non-neuronal cells. T3 also does not seem to
      enhance differentiated GABA functions (uptake or synthesis) beyond the levels
      achieved using insulin, progesterone, putrescine, selenium and transferrin. 

PMID- 24874044
TI  - Cerebellar DNA and tissue water changes in the brain of diabetes insipidus
      brattleboro rats are already present at birth.
AB  - Homozygous (HOM) Brattleboro rat newborns, congenitally lacking vasopressin,
      weighed less than heterozygous controls born from HOM females and reared as 9-pup
      litters. Whole brain and specific brain regions (cerebral cortex, medulla
      oblongata and colliculi but not the cerebellum) were also reduced in weight.
      Decreased tissue water content was observed in the regions affected in weight. In
      the cerebellum, on the other hand, a 20% lower DNA content was measured, which
      points to a prenatal origin for the impaired cerebellar neurogenesis which is
      known to exist postnatally. 

PMID- 24874043
TI  - Protein synthesis in cells isolated from the developing rat cerebellum.
AB  - The rate of protein synthesis was estimated in structurally preserved perikaryal
      preparations from 8-day-old rat cerebellum under conditions which overcome the
      problems of intracellular compartmentation. The rates were lower than the in vivo
      estimates at comparable ages, but they were of similar magnitude, and very much
      higher than previous estimates on isolated cells. Protein synthesis rate depended
      on the cell type. When expressed per cell the rank order in the preparations
      enriched in the indicated classes of cells was: Purkinje cells > astrocytes >
      granule cells in the S, G2 and M phase of the cell cycle > granule cells in G1
      and G0. However, after normalizing the results for size differences between cell
      types, by expressing the rates in terms of unit protein or as a percentage
      replacement of the protein bound amino acid, astrocytes and replicating granule
      cells displayed greater rates than the Purkinje cells. The resolution of labelled
      proteins using SDS-PAGE indicated marked differences in the rate of synthesis of
      particular proteins. The results were consistent with the view that certain
      polypeptides are uniquely expressed in particular cell classes. 

PMID- 24874045
TI  - Positive FAST without hemoperitoneum due to fluid resuscitation in blunt trauma.
AB  - BACKGROUND: The focused assessment with sonography in trauma (FAST) examination
      is an important screening tool in the evaluation of blunt trauma patients.
      OBJECTIVES: To describe a case of a hemodynamically unstable polytrauma patient
      with positive FAST due to fluid resuscitation after blunt trauma. CASE REPORT: We
      describe a case of a hemodynamically unstable polytrauma patient who underwent
      massive volume resuscitation prior to transfer from a community hospital to a
      trauma center. On arrival at the receiving institution, the FAST examination was
      positive for free intraperitoneal fluid, but no hemoperitoneum or significant
      intra-abdominal injuries were found during laparotomy. In this case, it is
      postulated that transudative intraperitoneal fluid secondary to massive volume
      resuscitation resulted in a positive FAST examination. CONCLUSION: This case
      highlights potential issues specific to resuscitated trauma patients with
      prolonged transport times. Further study is likely needed to assess what changes,
      if any, should be made in algorithms to address the effect of prior resuscitative
      efforts on the test characteristics of the FAST examination.

PMID- 24874046
TI  - All-time high tularaemia incidence in Norway in 2011: report from the national
      surveillance.
AB  - Tularaemia has mainly been a sporadic disease in Norway. In 2011, 180 persons
      (3.7 per 100,000 population) were diagnosed with tularaemia. This article
      describes the epidemiological and clinical features of tularaemia cases during a
      year with exceptionally high tularaemia incidence. Data from the national
      reference laboratory for tularaemia combined with epidemiological data from the
      Norwegian Surveillance System for Communicable Diseases (MSIS) were used. The
      incidence of tularaemia varied greatly between counties, but almost every county
      was involved. The majority (77.8 %) of the cases were diagnosed during the autumn
      and winter months. The geographic distribution also showed seasonal patterns.
      Overall, oropharyngeal tularaemia (41.1 %) was the most common clinical
      presentation, followed by glandular (14.4 %), typhoidal (14.4 %), respiratory
      (13.3 %) and ulceroglandular (12.8 %) tularaemia. From January to April,
      oropharyngeal tularaemia dominated, from May to September, ulceroglandular
      tularaemia was most common, whereas from October to December, there was an almost
      even distribution between several clinical forms of tularaemia. Eighty-five (47.2
      %) of all tularaemia cases were admitted to, or seen as outpatients in,
      hospitals. An unexpectedly high number (3.9 %) of the patients had positive blood
      culture with Francisella tularensis. The clinical manifestations of tularaemia in
      Norway in 2011 were diverse, and changing throughout the year. Classification was
      sometimes difficult due to uncharacteristic symptoms and unknown mode of
      transmission. In rodent years, tularaemia is an important differential diagnosis
      to keep in mind at all times of the year for a variety of clinical symptoms.

PMID- 24874047
TI  - Residual findings.

PMID- 24874049
TI  - Circulating soluble advanced glycation end product is inversely associated with
      the significant risk of developing cancer: evidence from a meta-analysis.
AB  - Currently, advanced glycation end product (RAGE) is receiving much attention in
      carcinogenesis research due to its involvement in cancer progression and
      metastasis. We therefore sought to examine the association of circulating soluble
      RAGE (sRAGE) with all types of cancer by a meta-analysis. The PubMed and EMBASE
      databases were searched before March 1, 2014. Data and study quality were
      assessed in duplicate. Effect estimates were expressed as weighted mean
      difference (WMD) and its 95 % confidence interval (CI). Altogether, nine eligible
      articles including 1,337 cancer patients and 1,839 controls were analyzed. The
      overall analysis indicated that circulating sRAGE was remarkably reduced by
      222.07 pg/ml in cancer patients compared with controls (95 % CI: -373.77 to 
      70.37; P = 0.004), with heterogeneity and without publication bias. In subgroup
      analyses, this reduction was weakened yet still significant in prospective
      studies (WMD = -87.62; 95 % CI: -138.60 to -36.63; P = 0.001) with improved
      heterogeneity (I (2) = 56.5 %; P = 0.056). Restricting analyses to the large
      studies (total number of subjects >=200) identified significant reduction of
      circulating sRAGE in cancer patients relative to controls (WMD = -231.34; 95 %
      CI: -450.10 to -12.58; P = 0.038). Further meta-regression analysis showed that
      smoking status explained some part of heterogeneity for the association of
      circulating sRAGE with cancer risk (regression coefficient: -67.02; P = 0.046).
      Our findings demonstrate a protective role of circulating sRAGE in the
      development of cancer, especially in patients without diabetes mellitus or with
      normal renal function.

PMID- 24874051
TI  - MiR-195 inhibits the growth and metastasis of NSCLC cells by targeting IGF1R.
AB  - MicroRNAs (miRNAs) are small, non-coding RNAs which act as oncogenes or tumor
      suppressors in multiple human cancers. Accumulating evidence reveals that
      aberrant expression of miRNAs contributes to the development and progression of
      non-small cell lung cancer (NSCLC). Here, we identified miR-195 as a tumor
      suppressor in NSCLC cells, whose expression level was dramatically decreased in
      both NSCLC tissues and cell lines. Ectopic expression of miR-195 suppressed NSCLC
      cell proliferation and metastasis-related traits in vitro. Insulin-like growth
      factor 1 receptor (IGF1R) was identified as a direct target of miR-195 in NSCLC
      cells. Furthermore, restoration of IGF1R remarkably attenuated the tumor
      suppressive effects of miR-195 on NSCLC cells. Our data suggest that miR-195 may
      be involved in the carcinogenesis of NSCLC partially by targeting IGF1R.

PMID- 24874050
TI  - The addition of mifamurtide to chemotherapy improves lifetime effectiveness in
      children with osteosarcoma: a Markov model analysis.
AB  - In the absence of long-term clinical trials that compare mifamurtide plus
      chemotherapy versus chemotherapy only for treatment of osteosarcoma, decision
      analysis is a useful tool that helps to determine the optimal treatment strategy.
      We analyzed the differences between mifamurtide plus chemotherapy versus
      chemotherapy only by using modeling to determine the treatment approach that
      results in longer life expectancy among children with osteosarcoma. We used the
      Markov model to compare the expected lifetime quality-adjusted life years (QALYs)
      between mifamurtide plus chemotherapy versus chemotherapy only. Our target cohort
      consisted of children with osteosarcoma. The starting age of the cohort was 12
      years and cycle length was 3 months. The transition probabilities for each
      disease state and death were calculated using overall survival or progression
      free survival data from randomized controlled trials. Utility weights from
      scenario-based survey for 303 Korean general populations were applied to the
      model. Based on the base case analysis, the incremental benefit analysis
      indicated that mifamurtide plus chemotherapy resulted in an incremental QALY
      increase of 1.57 (a relative increase of 16.3 % in QALY expectancy) compared to
      chemotherapy only. Also, the incremental life years gained (LYG) from mifamurtide
      plus chemotherapy was 1.96 on comparison with chemotherapy only; this is a
      relative increase of 15.7 % in LYG expectancy. The decision analysis model
      indicated that mifamurtide plus chemotherapy was associated with a substantially
      longer survival than chemotherapy only among children with osteosarcoma during
      their lifetime.

PMID- 24874052
TI  - Expression of MLH1 and MSH2 in urothelial carcinoma of the renal pelvis.
AB  - In this study, we investigated microsatellite instability in urothelial carcinoma
      of the renal pelvis by lack of immunohistochemical staining for MLH1 and MSH2.
      The study included 44 cases of urothelial carcinoma of the renal pelvis obtained
      from radical nephroureterectomy specimens at our institution. We evaluated the
      loss of nuclear immunohistochemical staining of MLH1 and MSH2. Eight of 44 (18 %)
      patients had negative MLH1 expression and 25/44 (57 %) patients had negative MSH2
      expression. Six of 8 (75 %) patients with negative MLH1 expression were male and
      2/8 (25 %) patients were female. Nineteen of 25 (75 %) patients with negative
      MSH2 expression were male, and 6/25 (24 %) patients were female. Seven of 8 (88
      %) cases with negative MLH1 expression were high-grade urothelial carcinoma, and
      21/25 (84 %) cases with negative MSH2 expression were high-grade urothelial
      carcinoma. Twenty-one of 44 (48 %) cases had an inverted growth pattern, of which
      3/21 (14 %) cases had negative MLH1 expression and 14/21 (67 %) cases had
      negative MSH2 expression. Our study showed that microsatellite instability based
      on negative expression of MLH1 and MSH2 was more common in male patients with
      high-grade urothelial carcinoma. There is a strong correlation between inverted
      growth pattern and negative MSH2 expression. Microsatellite instability testing
      should be performed in patients with upper urinary tract carcinoma and may have
      prognostic value.

PMID- 24874054
TI  - How to optimize the sequential use of novel therapeutics in metastatic prostate
      cancer patients? Response should be found in prostate cancer tissue.

PMID- 24874053
TI  - Influence of interleukin-28B polymorphism on progression to hepatitis virus
      induced hepatocellular carcinoma.
AB  - Genetic variation of interleukin-28B (IL-28B) rs12979860 T/C polymorphism is
      associated with the immune response to interferon (IFN) therapy, which is applied
      in the treatment of chronic viral hepatitis induced by hepatitis B virus (HBV)
      and hepatitis C virus (HCV). These chronic liver diseases could progress to end
      stage liver diseases, such as hepatocellular carcinoma (HCC). The aim of this
      study was to clarify whether there exists a causal association between IL-28B
      rs12979860 T/C polymorphism and development of HCC. In a meta-analysis of six
      studies with 850 cases and 811 controls, we summarized the data on the
      association between IL-28B rs12979860 T/C polymorphism and HCC risk and
      calculated ORs and 95 % CIs to estimate the association strength. We observed
      that IL-28B rs12979860 T/C polymorphism was positively associated with overall
      HCC risk (TT vs. CC: OR = 2.38; 95 %, 1.60-3.55; TT vs CT + CC: OR = 1.79; 95 %,
      1.23-2.60). In the stratified analysis by ethnicity, the robust association
      retained in Caucasians with higher risk among TT carriers relative to the CC
      carriers. A similar trend was found in the studies of healthy controls when data
      were stratified by source of controls. The combined data suggest that IL-28B
      rs12979860 T/C polymorphism seems to augment the risk of developing HCC,
      especially in Caucasians.

PMID- 24874055
TI  - Reference ranges of blood flow in the major vessels of the normal human fetal
      circulation at term by phase-contrast magnetic resonance imaging.
AB  - BACKGROUND: Phase-contrast MRI with metric-optimized gating is a promising new
      technique for studying the distribution of the fetal circulation. However, mean
      and reference ranges for blood flow measurements made in the major fetal vessels
      using this technique are yet to be established. METHODS AND RESULTS: We measured
      flow in the major vessels of the fetal circulation in 40 late-gestation normal
      human fetuses using phase-contrast MRI (mean gestational age, 37 [SD=1.1] weeks).
      Flows were indexed to the fetal weight, which was estimated from the fetal volume
      calculated by MRI segmentation. The following mean flows (in mL/min per kilogram;
      +/-2SD) were obtained: combined ventricular output, 465 (351, 579); main
      pulmonary artery, 261 (169, 353); ascending aorta, 191 (121, 261); superior vena
      cava, 137 (77, 197); ductus arteriosus, 187 (109, 265); descending aorta, 252
      (160, 344); pulmonary blood flow, 77 (0, 160); umbilical vein, 134 (62, 206); and
      foramen ovale, 135 (37, 233). Expressed as percentages of the combined
      ventricular output, the mean flows+/-2 SD were as follows: main pulmonary artery,
      56 (44, 68); ascending aorta, 41 (29, 53); superior vena cava, 29 (15, 43);
      ductus arteriosus, 41 (25, 57); descending aorta, 55 (35, 75); pulmonary blood
      flow, 16 (0, 34); umbilical vein, 29 (11, 47); and foramen ovale, 29 (7, 51). A
      strong inverse relationship between foramen ovale shunt and pulmonary blood flow
      was noted (r=-0.64; P<0.0001). CONCLUSIONS: Although too small a sample size to
      provide normal ranges, these results are in keeping with those predicted in
      humans based on measurements made in fetal lambs using radioactive microspheres
      and provide preliminary reference ranges for the late-gestation human fetuses.
      The wide range we found in foramen ovale shunting suggests a degree of
      variability in the way blood is streamed through the fetal circulation.

PMID- 24874056
TI  - Feasibility of optical coherence tomography in children with Kawasaki disease and
      pediatric heart transplant recipients.
AB  - BACKGROUND: Optical coherence tomography (OCT) is a high-resolution intravascular
      imaging technique used in adults. We tested the hypothesis that OCT could
      identify coronary abnormalities not seen by angiography in children with a
      history of Kawasaki disease (KD) and pediatric heart transplant (TX) recipients.
      METHODS AND RESULTS: Patients with KD and TX recipients were evaluated between
      December 2012 and October 2013 with angiography and OCT (Ilumien System,
      LightLabs, St Jude Medical, Westford, MA). Modifications were made to the adult
      OCT protocol to adapt this technique for children. Serial cross-sectional area
      measurements of the lumen, intima, and media were made. Entire imaging data were
      analyzed for the presence of qualitative changes. Seventeen children were
      evaluated (5 patients with KD; 12 TX recipients). In patients with KD,
      angiography was normal. However, OCT imaging revealed that significant vessel
      wall abnormalities were present in all children including intimal thickening
      (intima/lumen cross-sectional area ratio>0.4), loss of the normal layered
      structure of the vessel wall, white thrombus, calcification, and
      neovascularization. There was extensive destruction of the internal elastic
      lamina. In TX recipients, angiography was normal; however, intimal thickening
      (intima/media cross-sectional area ratio>1) was seen in 9 of 12 patients. The
      median intima/media cross-sectional area ratio was 1.18. CONCLUSIONS: In this
      initial experience with OCT in children, we have identified significant coronary
      abnormalities with OCT that are angiographically silent in children with a
      history of coronary aneurysms because of KD and in pediatric TX recipients.

PMID- 24874062
TI  - Transition metal complexes with oligopeptides: single crystals and crystal
      structures.
AB  - The coordination chemistry of short chain peptides with transition metals is
      described in terms of the available crystal structures. Despite their high
      interest as synthetic models for metalloproteins and as building blocks for
      molecular materials based on the tuneable properties of oligopeptides, single
      crystal X-ray diffraction studies are scarce. A perusal of the most relevant
      results in this field allows us to define the main characteristics of
      oligopeptide-metal interactions, the fundamental problems for the crystallization
      of these complexes, and some hints to identify future promising approaches to
      advance the development of metallopeptide chemistry. 

PMID- 24874061
TI  - Developmental oestrogen exposure differentially modulates IGF-I and TNF-alpha
      expression levels in immune organs of Yersinia ruckeri-challenged young adult
      rainbow trout (Oncorhynchus mykiss).
AB  - Intensified aquaculture has strong impact on fish health by stress and infectious
      diseases and has stimulated the interest in the orchestration of cytokines and
      growth factors, particularly their influence by environmental factors, however,
      only scarce data are available on the GH/IGF-system, central physiological system
      for development and tissue shaping. Most recently, the capability of the host to
      cope with tissue damage has been postulated as critical for survival. Thus, the
      present study assessed the combined impacts of estrogens and bacterial infection
      on the insulin-like growth factors (IGF) and tumor-necrosis factor (TNF)-alpha.
      Juvenile rainbow trout were exposed to 2 different concentrations of 17beta
      estradiol (E2) and infected with Yersinia ruckeri. Gene expressions of IGF-I, IGF
      II and TNF-alpha were measured in liver, head kidney and spleen and all 4
      estrogen receptors (ERalpha1, ERalpha2, ERbeta1 and ERbeta2) known in rainbow
      trout were measured in liver. After 5 weeks of E2 treatment, hepatic up
      regulation of ERalpha1 and ERalpha2, but down-regulation of ERbeta1 and ERbeta2
      were observed in those groups receiving E2-enriched food. In liver, the results
      further indicate a suppressive effect of Yersinia-infection regardless of E2
      treatment on day 3, but not of E2-treatment on IGF-I whilst TNF-alpha gene
      expression was not influenced by Yersinia-infection but was reduced after 5 weeks
      of E2-treatment. In spleen, the results show a stimulatory effect of Yersinia
      infection, but not of E2-treatment on both, IGF-I and TNF-alpha gene expressions.
      In head kidney, E2 strongly suppressed both, IGF-I and TNF-alpha. To summarise,
      the treatment effects were tissue- and treatment-specific and point to a relevant
      role of IGF-I in infection.

PMID- 24874063
TI  - Synthesis, structure and reactivity of a 1-bromoalumole.
AB  - A stable 1-bromoalumole has been synthesized by the reaction of a 1,4-dilithio
      1,3-butadiene derivative with AlBr3. The 1-bromoalumole was found to exist as a
      dimeric structure in the crystalline state. Reaction of the 1-bromoalumole with
      Mes*Li afforded the corresponding Mes*-substituted alumole (Mes* = 2,4,6-(t
      Bu)3C6H2), demonstrating the potential of the 1-bromoalumole for the
      functionalization of alumoles. 

PMID- 24874072
TI  - Assessing clinical practice of student nurses: Views of teachers, mentors and
      students.
AB  - BACKGROUND: Assessment received by students affects the way that they conduct
      their studies and shapes their interests in clinical placements. It is therefore
      important that mentors and teachers have high quality assessment strategies to
      ensure the competence of nursing students. OBJECTIVES: The objective of this
      study is to describe the views and experiences of nursing students, nursing
      teachers, and mentors on the final assessment of nursing students in clinical
      practice. The study also investigates respondents' views on using a standardized
      national or European scheme for clinical assessment in the future. DESIGN:
      Descriptive survey design with a questionnaire. SETTINGS: Implemented in five
      Finnish universities of applied sciences and in five partner hospitals.
      PARTICIPANTS: Nursing students (n=276), nursing teachers (n=108) and mentors
      (n=225). METHODS: A questionnaire was used to collect data. Survey data were
      analyzed by using SPSS version 19. Descriptive statistics and cross tabulations
      were used to characterize the data. RESULTS: Nursing students felt that they had
      spent enough time with their mentors during their clinical practice period to
      ensure that the mentors could assess their behavior. Mentors also evaluated that
      they had spent enough time with the students. Students and mentors both indicated
      occasional difficulties with the language used in the competence assessment
      document. Most of the nursing students and mentors shared the view that it is
      always necessary for a teacher to be involved in the final assessment discussion.
      CONCLUSIONS: The study highlights the importance of assessment skills of mentors
      and the important role of the teachers. Findings from this study indicate that
      nursing students' clinical practice assessment already includes many good
      practices, but we still have some difficulties in ensuring effective measures of
      competence.

PMID- 24874071
TI  - An aberrant leukotriene A4 hydrolase-proline-glycine-proline pathway in the
      pathogenesis of chronic obstructive pulmonary disease.
AB  - RATIONALE: Chronic neutrophilic inflammation is a hallmark in the pathogenesis of
      chronic obstructive pulmonary disease (COPD) and persists after cigarette smoking
      has stopped. Mechanisms involved in this ongoing inflammatory response have not
      been delineated. OBJECTIVES: We investigated changes to the leukotriene A4
      hydrolase (LTA4H)-proline-glycine-proline (PGP) pathway and chronic inflammation
      in the development of COPD. METHODS: A/J mice were exposed to air or cigarette
      smoke for 22 weeks followed by bronchoalveolar lavage and lung and cardiac tissue
      analysis. Two human cohorts were used to analyze changes to the LTA4H-PGP pathway
      in never smokers, control smokers, COPD smokers, and COPD former smokers.
      PGP/AcPGP and LTA4H aminopeptidase activity were detected by mass spectroscopy,
      LTA4H amounts were detected by ELISA, and acrolein was detected by Western blot.
      MEASUREMENTS AND MAIN RESULTS: Mice exposed to cigarette smoke developed
      emphysema with increased PGP, neutrophilic inflammation, and selective inhibition
      of LTA4H aminopeptidase, which ordinarily degrades PGP. We recapitulated these
      findings in smokers with and without COPD. PGP and AcPGP are closely associated
      with cigarette smoke use. Once chronic inflammation is established, changes to
      LTA4H aminopeptidase remain, even in the absence of ongoing cigarette use.
      Acrolein modifies LTA4H and inhibits aminopeptidase activity to the same extent
      as cigarette smoke. CONCLUSIONS: These results demonstrate a novel pathway of
      aberrant regulation of PGP/AcPGP, suggesting this inflammatory pathway may be
      intimately involved in disease progression in the absence of ongoing cigarette
      smoke exposure. We highlight a mechanism by which acrolein potentiates
      neutrophilic inflammation through selective inhibition of LTA4H aminopeptidase
      activity. Clinical trial registered with www.clinicaltrials.gov (NCT 00292552).

PMID- 24874073
TI  - Developing and piloting the multiple mini-interview in pre-registration student
      midwife selection in a UK setting.
AB  - BACKGROUND: Published research has demonstrated that the multiple mini-interview
      (MMI) is a reliable assessment instrument in medical and nursing student
      selection. There is a dearth of evidence specifically relating to the advancement
      and subsequent evaluation of MMIs in the context of student midwife selection.
      OBJECTIVES: To develop, pilot and examine the reliability of MMIs in pre
      registration student midwife selection in a UK setting. DESIGN AND SETTING:
      DeVellis' framework for questionnaire development underpinned the generation of
      MMI scenarios. BSc (Hons) Midwifery Studies students at a Higher Education
      Institution in the UK volunteered to participate in 'mock' MMI circuits during
      the first week of their programme. RESULTS: An eight station model was piloted.
      Communication skills were rated at each station as a generic attribute. Station
      specific attributes assessed included: compassion and empathy; respect for
      difference and diversity; honesty and integrity; intellectual curiosity and
      reflective nature; advocacy; respect for privacy and dignity; team working and
      initiative; the role of the midwife and motivation to become a midwife.
      Participants' responses to scenario questions were rated on a 7 point scale.
      Cronbach's alpha scores measuring internal consistency ranged from 0.91 to 0.97
      CONCLUSION: The systematic development of the MMI model and scenarios resulted in
      'excellent' reliability across all stations. These findings endorse the MMI
      technique as a reliable alternative to the personal interview in informing final
      decisions in pre-registration student midwife selection.

PMID- 24874074
TI  - Lights and shadows on food microfluidics.
AB  - These insights attempt to share with the community the lights and shadows of one
      emerging and exciting topic, Food Microfluidics, defined as microfluidic
      technology for food analysis and diagnosis in important areas such as food safety
      and quality. The reader is invited to question non-easy interrogations such as
      why Food Microfluidics, what is the next step and what could we do with the
      available technology. This article invites food analysts to be seduced by this
      technology and then to take an interesting trip departing from the main gained
      achievements, having a look at the crossing bridges over Food Microfluidic
      challenges or having a look at available technology to start. Finally, this trip
      arrives at a privileged place to gaze the horizons. A wonderful landscape--full
      of inspiration--for Food Microfluidics is anticipated. These insights have also
      been written wishing to give improved conceptual and realistic solutions for food
      analysis, with the additional hope to attract the community with exciting
      technology, in order to get novel and unexpected achievements in this field.

PMID- 24874075
TI  - Mutant LRRK2 enhances glutamatergic synapse activity and evokes excitotoxic
      dendrite degeneration.
AB  - Mutations in leucine-rich repeat kinase 2 (LRRK2), which are associated with
      autosomal dominant Parkinson's disease, elicit progressive dendrite degeneration
      in neurons. We hypothesized that synaptic dysregulation contributes to mutant
      LRRK2-induced dendritic injury. We performed in vitro whole-cell voltage clamp
      studies of glutamatergic receptor agonist responses and glutamatergic synaptic
      activity in cultured rat cortical neurons expressing full-length wild-type and
      mutant forms of LRRK2. Expression of the pathogenic G2019S or R1441C LRRK2
      mutants resulted in larger whole-cell current responses to direct application of
      AMPA and NMDA receptor agonists. In addition, mutant LRRK2-expressing neurons
      exhibited an increased frequency of spontaneous miniature excitatory postsynaptic
      currents (mEPSCs) in conjunction with increased excitatory synapse density as
      assessed by immunofluorescence for PSD95 and VGLUT1. Mutant LRRK2-expressing
      neurons showed enhanced vulnerability to acute synaptic glutamate stress.
      Furthermore, treatment with the NMDA receptor antagonist memantine significantly
      protected against subsequent losses in dendrite length and branching complexity.
      These data demonstrate an early association between mutant LRRK2 and increased
      excitatory synapse activity, implicating an excitotoxic contribution to mutant
      LRRK2 induced dendrite degeneration. 

PMID- 24874076
TI  - A novel protective mechanism for mitochondrial aldehyde dehydrogenase (ALDH2) in
      type i diabetes-induced cardiac dysfunction: role of AMPK-regulated autophagy.
AB  - Mitochondrial aldehyde dehydrogenase (ALDH2) is known to offer myocardial
      protection against stress conditions including ischemia-reperfusion injury,
      alcoholism and diabetes mellitus although the precise mechanism is unclear. This
      study was designed to evaluate the effect of ALDH2 on diabetes-induced myocardial
      injury with a focus on autophagy. Wild-type FVB and ALDH2 transgenic mice were
      challenged with streptozotozin (STZ, 200mg/kg, i.p.) for 3months to induce
      experimental diabetic cardiomyopathy. Diabetes triggered cardiac remodeling and
      contractile dysfunction as evidenced by cardiac hypertrophy, decreased cell
      shortening and prolonged relengthening duration, the effects of which were
      mitigated by ALDH2. Lectin staining displayed that diabetes promoted cardiac
      hypertrophy, the effect of which was alleviated by ALDH2. Western blot analysis
      revealed dampened autophagy protein markers including LC3B ratio and Atg7 along
      with upregulated p62 following experimental diabetes, the effect of which was
      reconciled by ALDH2. Phosphorylation level of AMPK was decreased and its
      downstream signaling molecule FOXO3a was upregulated in both diabetic cardiac
      tissue and in H9C2 cells with high glucose exposure. All these effect were partly
      abolished by ALDH2 overexpression and ALDH2 agonist Alda1. High glucose challenge
      dampened autophagy in H9C2 cells as evidenced by enhanced p62 levels and
      decreased levels of Atg7 and LC3B, the effect of which was alleviated by the
      ALDH2 activator Alda-1. High glucose-induced cell death and apoptosis were
      reversed by Alda-1. The autophagy inhibitor 3-MA and the AMPK inhibitor compound
      C mitigated Alda-1-offered beneficial effect whereas the autophagy inducer
      rapamycin mimicked or exacerbated high glucose-induced cell injury. Moreover,
      compound C nullified Alda-1-induced protection against STZ-induced changes in
      autophagy and function. Our results suggested that ALDH2 protects against
      diabetes-induced myocardial dysfunction possibly through an AMPK -dependent
      regulation of autophagy. This article is part of a Special Issue entitled:
      Autophagy and protein quality control in cardiometabolic diseases. 

PMID- 24874078
TI  - Synthesis and analysis of a family of cerium(IV) halide and pseudohalide
      compounds.
AB  - The first complete series of isostructural cerium(IV) halide complexes in a
      conserved ligand framework was isolated by halogen-exchange reactions of
      CeF[N(SiMe3)2]3 with Me3SiX (X = Cl(-), Br(-), I(-)). The use of Me3SiX reagents
      represents a useful method for obtaining cerium(IV) complexes. Spectroscopic,
      electrochemical, and computational analyses were used to describe the effects of
      halide coordination on the cerium(IV) metal center. Cerium(IV) complexes of the
      pseudohalide ligands: N3(-) and NCS(-) were also synthesized and evaluated in
      comparison to the halide congeners. The results showed that the complexes
      exhibited reduction potentials and electronic absorption energies that varied
      with the identity of the halide or pseudohalide ligand. 

PMID- 24874077
TI  - Leptin attenuates BACE1 expression and amyloid-beta genesis via the activation of
      SIRT1 signaling pathway.
AB  - The aspartyl protease beta-site AbetaPP-cleaving enzyme 1 (BACE1) catalyzes the
      rate-limiting step in Abeta production, a peptide at the nexus of
      neurodegenerative cascades in Alzheimer Disease (AD). The adipocytokine leptin
      has been demonstrated to reduce Abeta production and decrease BACE1 activity and
      expression levels. However, the signaling cascades involved in the leptin-induced
      mitigation in Abeta levels and BACE1 expression levels have not been elucidated.
      We have demonstrated that the transcription factor nuclear factor - kappa B (NF
      kappaB) positively regulates BACE1 transcription. NF-kappaB activity is tightly
      regulated by the mammalian sirtuin SIRT1. Multiple studies have cogently evinced
      that leptin activates the metabolic master regulator SIRT1. In this study, we
      determined the extent to which SIRT1 expression and activity regulate the leptin
      induced attenuation in BACE1 expression and Abeta levels in cultured human
      neuroblastoma SH-SY5Y cells. This study also elucidated and delineated the signal
      transduction pathways involved in the leptin induced mitigation in BACE1
      expression. Our results demonstrate for the first time that leptin attenuates the
      activation and transcriptional activity of NF-kappaB by reducing the acetylation
      of the p65 subunit in a SIRT1-dependent manner. Furthermore, our data shows that
      leptin reduces the NF-kappaB-mediated transcription of BACE1 and consequently
      reduces Amyloid-beta genesis. Our study provides a valuable insight and a novel
      mechanism by which leptin reduces BACE1 expression and Amyloid-beta production
      and may help design potential therapeutic interventions. 

PMID- 24874079
TI  - Changes of polyamine pattern in digestive glands of mussel Mytilus
      galloprovincialis under exposure to cadmium.
AB  - Polyamines, in particular spermidine and spermine, have been identified as
      important antioxidants, highly induced by oxidative stress in a variety of
      organisms. However, little is known about changes in polyamine content of metal
      stressed marine organisms. In the present study, mussels (Mytilus
      galloprovincialis) were experimentally exposed to 25 MUg/L Cd(2+) or 100 MUg/L
      Cd(2+) for up to 15 days. Cd(2+) was progressively accumulated in mussel tissues,
      leading to a characteristic oxidative-stress status. Free putrescine (PUT)
      production was noticeably induced in response to Cd(2+) at day 5 and then
      declined. In contrast, free spermidine (SPD) content was gradually reduced,
      whereas the concentration of free spermine (SPM) increased. In combination, these
      changes led to a 69% or 88% reduction in the ratio of (SPD+SPM)/PUT at day 5,
      dependent on the Cd(2+) concentration used, which subsequently followed an upward
      trend in values, albeit not reaching those of controls. Conjugated polyamines
      constantly increased, in particular conjugated spermidine and spermine, tagging
      along with metallothionein production. Acetylated polyamines showed a diverse
      profile of changes, but their content was generally kept at low levels throughout
      the exposure period. Collectively, our results suggest that certain polyamine
      compounds could play a significant role in the tolerance of mussels against
      Cd(2+)-mediated stress, and that the ratio (SPD+SPM)/PUT could be a good
      indicator of the metal-stress status.

PMID- 24874080
TI  - In vitro and in vivo effects of phytoestrogens on protein turnover in rainbow
      trout (Oncorhynchus mykiss) white muscle.
AB  - Soybeans and other legumes investigated as fishmeal replacements in aquafeeds
      contain phytoestrogens capable of binding to and activating estrogen receptors.
      Estradiol has catabolic effects in salmonid white muscle, partially through
      increases in protein turnover. The current study determines whether
      phytoestrogens promote similar effects. In rainbow trout (Oncorhynchus mykiss)
      primary myocyte cultures, the phytoestrogens genistein, daidzein, glycitein, and
      R- and S-equol reduced rates of protein synthesis and genistein, the
      phytoestrogen of greatest abundance in soy, also increased rates of protein
      degradation. Increased expression of the ubiquitin ligase fbxo32 and autophagy
      related genes was observed with high concentrations of genistein (100 MUM), and R
      and S-equol (100 MUM) also up-regulated autophagy-related genes. In contrast,
      low genistein concentrations in vitro (0.01-0.10 MUM) and in vivo (5 MUg/g body
      mass) decreased fbxo32 expression, suggesting a potential metabolic benefit for
      low levels of genistein exposure. Phytoestrogens reduced cell proliferation,
      indicating that effects of phytoestrogens extend from metabolic to mitogenic
      processes. Co-incubation of genistein with the estrogen receptor (ER) antagonist,
      ICI 182,780, ameliorated effects of genistein on protein degradation, but not
      protein synthesis or cell proliferation, indicating that effects of genistein are
      mediated through ER-dependent and ER-independent mechanisms. Collectively, these
      data warrant additional studies to determine the extent to which dietary
      phytoestrogens, especially genistein, affect physiological processes that impact
      growth and nutrient retention.

PMID- 24874081
TI  - Evaluation of algal biofilms on indium tin oxide (ITO) for use in biophotovoltaic
      platforms based on photosynthetic performance.
AB  - In photosynthesis, a very small amount of the solar energy absorbed is
      transformed into chemical energy, while the rest is wasted as heat and
      fluorescence. This excess energy can be harvested through biophotovoltaic
      platforms to generate electrical energy. In this study, algal biofilms formed on
      ITO anodes were investigated for use in the algal biophotovoltaic platforms.
      Sixteen algal strains, comprising local isolates and two diatoms obtained from
      the Culture Collection of Marine Phytoplankton (CCMP), USA, were screened and
      eight were selected based on the growth rate, biochemical composition and
      photosynthesis performance using suspension cultures. Differences in biofilm
      formation between the eight algal strains as well as their rapid light curve
      (RLC) generated using a pulse amplitude modulation (PAM) fluorometer, were
      examined. The RLC provides detailed information on the saturation characteristics
      of electron transport and overall photosynthetic performance of the algae. Four
      algal strains, belonging to the Cyanophyta (Cyanobacteria) Synechococcus
      elongatus (UMACC 105), Spirulina platensis. (UMACC 159) and the Chlorophyta
      Chlorella vulgaris (UMACC 051), and Chlorella sp. (UMACC 313) were finally
      selected for investigation using biophotovoltaic platforms. Based on power output
      per Chl-a content, the algae can be ranked as follows: Synechococcus elongatus
      (UMACC 105) (6.38*10(-5) Wm(-2)/ugChl-a)>Chlorella vulgaris UMACC 051 (2.24*10(
      5) Wm(-2)/ugChl-a)>Chlorella sp.(UMACC 313) (1.43*10(-5) Wm(-2)/ugChl
      a)>Spirulina platensis (UMACC 159) (4.90*10(-6) Wm(-2)/ugChl-a). Our study showed
      that local algal strains have potential for use in biophotovoltaic platforms due
      to their high photosynthetic performance, ability to produce biofilm and
      generation of electrical power.

PMID- 24874082
TI  - Uncertainty in model predictions of Vibrio vulnificus response to climate
      variability and change: a Chesapeake Bay case study.
AB  - The effect that climate change and variability will have on waterborne bacteria
      is a topic of increasing concern for coastal ecosystems, including the Chesapeake
      Bay. Surface water temperature trends in the Bay indicate a warming pattern of
      roughly 0.3-0.4 degrees C per decade over the past 30 years. It is unclear what
      impact future warming will have on pathogens currently found in the Bay,
      including Vibrio spp. Using historical environmental data, combined with three
      different statistical models of Vibrio vulnificus probability, we explore the
      relationship between environmental change and predicted Vibrio vulnificus
      presence in the upper Chesapeake Bay. We find that the predicted response of V.
      vulnificus probability to high temperatures in the Bay differs systematically
      between models of differing structure. As existing publicly available datasets
      are inadequate to determine which model structure is most appropriate, the impact
      of climatic change on the probability of V. vulnificus presence in the Chesapeake
      Bay remains uncertain. This result points to the challenge of characterizing
      climate sensitivity of ecological systems in which data are sparse and only
      statistical models of ecological sensitivity exist. 

PMID- 24874083
TI  - Diagnosis of late presenting subarachnoid hemorrhage: comparison of methods for
      cerebrospinal fluid ferritin.
AB  - BACKGROUND: The majority of subarachnoid hemorrhage (SAH) is diagnosed using
      imaging techniques. The sensitivity of computed tomography scans decreases with
      increasing time after the bleeding event which can lead to false negative CT
      scans. Spectrophotometry and microscopic investigations of the cerebrospinal
      fluid (Csf) can provide additional diagnostic support, but may not be available
      for emergency diagnoses. Csf-Ferritin has been suggested as an alternative
      additional marker for SAH that present late and has a potency to be measured in a
      routine laboratory. METHODS: A routine Ferritin chemiluminescent assay (Dimension
      Vista) was compared with a branded and CE-marked Csf-Ferritin nephelometric assay
      (BN ProSpec) using surplus routine patient samples. We calculated imprecision at
      pertinent concentrations, compared patient samples, and established reference
      intervals. RESULTS: The standard deviation was about a third for the Dimension
      Vista assay compared to that of the BN ProSpec assay at the three tested
      concentrations. The correlation showed a systematic difference between the
      methods but the correlation was high (r = 0.955). Accordingly, the reference
      intervals were higher for the BN ProSPec (2.7-16.8 MUg/L) than for the Dimension
      Vista (2.0-12.6 MUg/L). CONCLUSION: The precision of the Dimension Vista
      measurements was considerably better than that of the BN ProSpec. The Dimension
      Vista results correlated well with those of the comparative method, yielding
      slightly lower values. This is reflected in the reference intervals. These
      findings permit the use of the routinely available Ferritin assay of the
      Dimension Vista for measuring Csf-Ferritin and complementing the late diagnosis
      of SAH outside office hours of specialized Csf laboratories.

PMID- 24874084
TI  - MicroRNA expression profile in myocardial bridging patients.
AB  - BACKGROUND: Myocardial bridging (MB), a common benign coronary anomaly, may bring
      about some unwanted complications such as angina-like chest pain. The only way of
      MB detection is coronary arteriography or coronary computed tomographic
      angiography, which is costly and invasive. This study intended to profile a panel
      of circulating microRNAs (miRNAs) as potential biomarkers for the diagnosis of
      MB. METHODS: Using TaqMan Low-Density Array followed by quantitative reverse
      transcriptase PCR (qRT-PCR) validation, we analyzed the expression of miRNAs in
      serum samples from 90 MB patients and 50 non-MB controls. RESULTS: The Low
      Density Array data showed that 196 miRNAs were differentially expressed in MB
      patient sera in comparison with controls. After qRT-PCR validation and receiver
      operating characteristic (ROC) analysis, a list of five miRNAs (miR-29b, miR-151
      3p, miR-126, miR-503-3p and miR-645) showed the ability to distinguish MB
      patients from controls. The area under curve (AUC) values range from 0.722-0.938.
      CONCLUSIONS: We have demonstrated that this panel of five serum miRNAs is
      expected to become potential non-invasive biomarkers for detection of MB.

PMID- 24874085
TI  - Meta-analysis of Zn, Cu and Fe in the hair of Chinese children with recurrent
      respiratory tract infection.
AB  - Trace elements play an important role in maintaining the normal metabolic and
      immune function. The onset of recurrent respiratory tract infection (RRI) is
      associated with the immune function, genetic factors and nutritional status.
      However, the association between the levels of trace elements and RRI remains
      inconclusive. We aimed to investigate the alterations of hair levels of zinc
      (Zn), copper (Cu) and iron (Fe) in Chinese children with RRI by performing a meta
      analysis. A predefined electronic databases search was performed to identify
      eligible studies for the analysis of hair Zn, Cu or Fe levels in Chinese children
      with RRI. Thirteen studies were included. RRI patients displayed significantly
      lower levels of hair Zn (13 studies, random effects SMD: - 1.215, 95% CI: - 1.704
      to - 0.725, p < 0.0001), Cu (11 studies, random effects SMD: - 0.384, 95% CI: -
      0.717 to - 0.052, p = 0.023) and Fe (12 studies, random effects SMD: - 0.569, 95%
      CI: - 0.827 to - 0.312, p < 0.0001) compared with controls. No evidence of
      publication bias was observed. Sensitivity analysis did not change the results
      significantly. In conclusion, the deficiency of Zn, Cu and Fe may be contributing
      factors for the susceptibility of RRI in Chinese children. However, more studies
      in different ethnicities should be performed in the future.

PMID- 24874087
TI  - Toward an evidence-based step-up approach in diagnosing diverticulitis.
AB  - BACKGROUND: The lack of pathognomonic findings and the chance of complicated
      disease have resulted in the widespread use of additional imaging to diagnose
      acute colonic diverticulitis (ACD). The added value of additional imaging in the
      diagnostic workup of patients suspected of ACD is not well defined. AIMS: The aim
      of this study was to systematically review the literature of the accuracy of the
      clinical evaluation and diagnostic modalities for patients with suspected ACD, to
      come to an evidence-based approach to diagnose ACD. METHODS: A systematic review
      and meta-analysis of studies that reported diagnostic accuracy of the clinical
      diagnosis and diagnostic modalities in patients with suspected diverticulitis
      were performed. Study quality was assessed with the STARD checklist. True
      positive, true-negative, false-positive, and false-negative findings were
      extracted and pooled estimates of sensitivity and specificity per diagnostic test
      were calculated, if applicable. RESULTS: The overall quality of the studies
      reporting the diagnostic accuracy of the clinical diagnosis, contrast enema and
      magnetic resonance imaging (MRI) were moderate to poor and not suitable for meta
      analysis. Sensitivity of the clinical diagnosis varied between 64% and 68%.
      Ultrasound (US) and computed tomography (CT) studies were eligible for meta
      analysis. Summary sensitivity estimates for US were 90% (95% CI: 76-98%) versus
      95% (95% CI: 91-97%) for CT (p = 0.86). Summary specificity estimates for US were
      90% (95% CI: 86-94%) versus 96% (95% CI: 90-100%) for CT (p = 0.04). Sensitivity
      for MRI was 98% and specificity varied between 70% and 78%. Sensitivity of
      contrast enema studies varied between 80% and 83%. CONCLUSION: In two-thirds of
      the patients, the diagnosis of ACD can be made based on clinical evaluation
      alone. In one-third of the patients, additional imaging is a necessity to
      establish the diagnosis. US and CT are comparable in diagnosing diverticulitis
      and superior to other modalities. CT has the advantage of higher specificity and
      the ability to identify alternative diagnoses. The role of MRI is not yet clear
      in diagnosing ACD. Contrast enema is considered an obsolete imaging technique to
      diagnose ACD based on lower sensitivity and specificity than US and CT. A step-up
      approach with CT performed after an inconclusive or negative US, seems a logical
      and safe approach for patients suspected of ACD.

PMID- 24874086
TI  - The challenge of producing skin test antigens with minimal resources suitable for
      human application against a neglected tropical disease; leprosy.
AB  - True incidence of leprosy and its impact on transmission will not be understood
      until a tool is available to measure pre-symptomatic infection. Diagnosis of
      leprosy disease is currently based on clinical symptoms, which on average take 3
      10 years to manifest. The fact that incidence, as defined by new case detection,
      equates with prevalence, i.e., registered cases, suggests that the cycle of
      transmission has not been fully intercepted by implementation of multiple drug
      therapy. This is supported by a high incidence of childhood leprosy.
      Epidemiological screening for pre-symptomatic leprosy in large endemic
      populations is required to facilitate targeted chemoprophylactic interventions.
      Such a test must be sensitive, specific, simple to administer, cost-effective,
      and easy to interpret. The intradermal skin test method that measures cell
      mediated immunity was explored as the best option. Prior knowledge on skin
      testing of healthy subjects and leprosy patients with whole or partially
      fractionated Mycobacterium leprae bacilli, such as Lepromin or the Rees' or
      Convit' antigens, has established an acceptable safety and potency profile of
      these antigens. These data, along with immunoreactivity data, laid the foundation
      for two new leprosy skin test antigens, MLSA-LAM (M. leprae soluble antigen
      devoid of mycobacterial lipoglycans, primarily lipoarabinomannan) and MLCwA (M.
      leprae cell wall antigens). In the absence of commercial interest, the challenge
      was to develop these antigens under current good manufacturing practices in an
      acceptable local pilot facility and submit an Investigational New Drug to the
      Food and Drug Administration to allow a first-in-human phase I clinical trial. 

PMID- 24874088
TI  - Adverse surgical outcomes in screen-detected ductal carcinoma in situ of the
      breast.
AB  - BACKGROUND: The Sloane Project is the largest prospective audit of ductal
      carcinoma in situ (DCIS) worldwide, with over 12,000 patients registered between
      2003 and 2012, accounting for 50% of screen-detected DCIS diagnosed in the United
      Kingdom (UK) over the period of accrual. METHODS: Complete multidisciplinary data
      from 8313 patients with screen-detected DCIS were analysed for surgical outcome
      in relation to key radiological and pathological parameters for the cohort and
      also by hospital of treatment. Adverse surgical outcomes were defined as either
      failed breast conservation surgery (BCS) or mastectomy for small lesions (<20mm)
      (MFSL). Inter-hospital variation was analysed by grouping hospitals into high,
      medium and low frequency subgroups for these two adverse outcomes. RESULTS:
      Patients with failed BCS or MFSL together accounted for 49% of all mastectomies.
      Of 6633 patients embarking on BCS, 799 (12.0%) required mastectomy. MFSL
      accounted for 510 (21%) of 2479 mastectomy patients. Failed BCS was associated
      with significant radiological under-estimation of disease extent and MFSL
      significant radiological over-estimation of disease extent. There was
      considerable and significant inter-hospital variation in failed BCS (range 3-32%)
      and MFSL (0-60%) of a hospital's BCS/mastectomy workload respectively.
      Conversely, there were no differences between the key radiological and
      pathological parameters in high, medium and low frequency adverse-outcome
      hospitals. CONCLUSIONS: This evidence suggests significant practice variation,
      not patient factors, is responsible for these adverse surgical outcomes in screen
      detected DCIS. The Sloane Project provides an evidence base for future practice
      benchmarking.

PMID- 24874090
TI  - The sick child in early modern England, 1580-1720.

PMID- 24874091
TI  - Traumatic proximal aortic arch injuries with contralateral aortic disruption.

PMID- 24874093
TI  - Palladium-catalyzed dearomative trimethylenemethane cycloaddition reactions.
AB  - A general protocol for the palladium-catalyzed dearomative trimethylenemethane
      [3+2] cycloaddition reaction with simple nitroarene substrates is described. This
      methodology leads to the exclusive formation of the dearomatized alicyclic
      products without subsequent rearomatization. The reaction is tolerant toward a
      broad range of heterocyclic and benzenoid substrates. The use of chiral
      bisdiamidophosphite ligands enabled the development of an enantioselective
      variant of this transformation, representing one of the rare examples of an
      asymmetric catalytic dearomatization process. 

PMID- 24874089
TI  - Large scale RNAi reveals the requirement of nuclear envelope breakdown for
      nuclear import of human papillomaviruses.
AB  - A two-step, high-throughput RNAi silencing screen was used to identify host cell
      factors required during human papillomavirus type 16 (HPV16) infection. Analysis
      of validated hits implicated a cluster of mitotic genes and revealed a previously
      undetermined mechanism for import of the viral DNA (vDNA) into the nucleus. In
      interphase cells, viruses were endocytosed, routed to the perinuclear area, and
      uncoated, but the vDNA failed to be imported into the nucleus. Upon nuclear
      envelope perforation in interphase cells HPV16 infection occured. During mitosis,
      the vDNA and L2 associated with host cell chromatin on the metaphase plate.
      Hence, we propose that HPV16 requires nuclear envelope breakdown during mitosis
      for access of the vDNA to the nucleoplasm. The results accentuate the value of
      genes found by RNAi screens for investigation of viral infections. The list of
      cell functions required during HPV16 infection will, moreover, provide a resource
      for future virus-host cell interaction studies. 

PMID- 24874094
TI  - The biodegradation and COD removal of 2-chlorophenol in a granular anoxic baffled
      reactor.
AB  - The present work was designed to developed a granular anoxic baffled reactor
      (AnBR) and to investigate its performance in the treatment of 2-chlorophenol (2
      CP). The acclimation and enrichment of microorganisms in activated sludge to
      degrade 2-CP was effectively accomplished. Then the influence of inlet 2-CP,
      hydraulic retention time (HRT), salinity, and type of electron acceptor (nitrate
      or organic compound) on the performance of AnBR in biodegradation of 2-CP was
      investigated. The increase of inlet 2-CP from 50 to 500mg/L at a fixed HRT of 24h
      did not adversely affected the AnBR where over 99% of inlet 2-CP was biodegraded.
      Decreasing the HRT stepwise from 24 to 4h at an inlet 2-CP of 200mg/L did not
      inhibit the rate of biodegradation (>99%). The increase of over 20g/L salinity in
      the feed stream strongly inhibited the rate of 2-CP biodegradation in the AnBR,
      whereas the bioreactor could efficiently tolerate concentrations below 20g/L
      NaCl. Moreover, the rate of 2-CP biodegradation under anoxic denitrifying
      metabolic conditions (presence of nitrate) was much greater than that under
      anaerobic metabolic conditions (absence of nitrate). Accordingly, the AnBR
      process is a feasible, simple, low-cost, and thus appropriate process for
      efficiently biodegrading toxic chlorinated organic compounds. 

PMID- 24874095
TI  - Immobilization of (R)- and (S)-amine transaminases on chitosan support and their
      application for amine synthesis using isopropylamine as donor.
AB  - Transaminases from Aspergillus fumigatus ((R)-selective, AspFum), Ruegeria
      pomeroyi ((S)-selective, 3HMU) and Rhodobacter sphaeroides 2.4.1 ((S)-selective,
      3I5T) were immobilized on chitosan with specific activities of 99, 157, and
      163U/g and acceptable yields (54, 21, and 23%, respectively) for glutaraldehyde
      (GA) immobilization. Besides GA, also divinylsulfone was used as linker molecule
      leading to a similar efficient immobilization for two enzymes, GibZea and NeoFis,
      whereas GA was superior in the other cases. Storage of the GA-immobilized enzymes
      for one month resulted in increased relative activities between 120 and 180%. The
      thermal stability was improved, especially for the GA-immobilized AspFum compared
      to the free enzyme after incubation for 4h at 60 degrees C (10% vs. 235% residual
      activity). Especially after incubation of AspFum (free or immobilized) for 2h at
      50 degrees C a strongly increased activity was observed (up to 359% of the
      initial activity). This effect was studied in more detail, revealing that one
      heat activation prior and one after immobilization increased the overall
      immobilization efficiency. Recycling of the immobilized ATAs resulted only in a
      small reduction of activity after four batches. Asymmetric synthesis of (R)- or
      (S)-1-methyl-3-phenylpropylamine from the prostereogenic ketone using
      isopropylamine (IPA) as amino donor was applied with conversions up to 50%
      (AspFum) or 75% (3HMU). Except for NeoFis, all immobilized ATAs showed higher
      conversions compared to the free enzyme. 

PMID- 24874096
TI  - Determination of the second autoproteolytic cleavage site of cephalosporin C
      acylase and the effect of deleting its flanking residues in the alpha-C-terminal
      region.
AB  - Self-activation through two-step intra-molecular cleavages is of great importance
      for the synthesis of mature and functional cephalosporin acylase in the N
      terminal nucleophile (Ntn) hydrolase superfamily. A synthetic gene for
      cephalosporin C acylase (sCPCAcy) from Pseudomonas sp. SE83 was overexpressed,
      and the self-activated sCPCAcy was produced in Escherichia coli JM109(DE3)/pET28
      sCPCAcy. The first autoproteolytic cleavage site of Pre-sCPCAcy was determined to
      be G239-S240 according to the common features of Ntn hydrolases. The second
      cleavage site was identified as A232-S233 by C-terminus tandem MS/MS analysis of
      the purified alpha-subunit, which released a 7-aa spacer peptide with the
      generation of the alpha and beta subunits of the mature sCPCAcy. The effect of
      the cleavage-site-flanking residues in the alpha-C-terminal region of sCPCAcy on
      its activation and characteristics was further evaluated. Residue G229 was found
      to be crucial for the first cleavage of Pre-sCPCAcy. Deletions in the alpha-C
      terminal region were performed, and 14 mutant proteins were constructed. The
      majority of the fragment-deleted mutant proteins completely lost their activity
      due to failure of the first autocleavage, but this loss was not observed in
      mutant proteins D2 (227-AM-228 deletion) and D4 (212-ADLA-215 deletion), which
      formally activated into mature sCPCAcy with high activity. The Kcat/Km values of
      mutant proteins D2 and D4 were 46% and 102% higher than that of the original
      control, respectively. 

PMID- 24874097
TI  - The selective formation of graphene ranging from two-dimensional sheets to three
      dimensional mesoporous nanospheres.
AB  - This research presents a template-free solvothermal method which offers selective
      preparation of graphene ranging from two-dimensional sheets to 3-dimensional
      nanospheres. The thus prepared nanospheres have size-defined mesopores with a
      huge surface area and, after doping with nitrogen, exhibited stronger
      electrocatalytic activity toward oxygen reduction than commercial Pt/C catalysts.

PMID- 24874099
TI  - Single bunch X-ray pulses on demand from a multi-bunch synchrotron radiation
      source.
AB  - Synchrotron radiation facilities routinely operate in a multi-bunch regime, but
      applications relying on time-of-flight schemes require single bunch operation.
      Here we show that pulse picking by resonant excitation in a storage ring creates
      in addition to the multi-bunch operation a distinct and separable single bunch
      soft X-ray source. It has variable polarization, a photon flux of up to 10(7)
      10(9) ph s(-1)/0.1%BW at purity values of 10(4)-10(2) and a repetition rate of
      1.25 MHz. The quasi-resonant excitation of incoherent betatron oscillations of
      electrons allows horizontal pulse separation at variable (also circular)
      polarization accessible for both, regular 30 ps pulses and ultrashort pulses of 2
      3 ps duration. Combined with a new generation of angularly resolving electron
      spectrometers this creates unique opportunities for time-resolved photoemission
      studies as confirmed by time-of-flight spectra. Our pulse picking scheme is
      particularly suited for surface physics at diffraction-limited light sources
      promising ultimate spectral resolution. 

PMID- 24874098
TI  - Separating NADH and NADPH fluorescence in live cells and tissues using FLIM.
AB  - NAD is a key determinant of cellular energy metabolism. In contrast, its
      phosphorylated form, NADP, plays a central role in biosynthetic pathways and
      antioxidant defence. The reduced forms of both pyridine nucleotides are
      fluorescent in living cells but they cannot be distinguished, as they are
      spectrally identical. Here, using genetic and pharmacological approaches to
      perturb NAD(P)H metabolism, we find that fluorescence lifetime imaging (FLIM)
      differentiates quantitatively between the two cofactors. Systematic manipulations
      to change the balance between oxidative and glycolytic metabolism suggest that
      these states do not directly impact NAD(P)H fluorescence decay rates. The
      lifetime changes observed in cancers thus likely reflect shifts in the NADPH/NADH
      balance. Using a mathematical model, we use these experimental data to quantify
      the relative levels of NADH and NADPH in different cell types of a complex
      tissue, the mammalian cochlea. This reveals NADPH-enriched populations of cells,
      raising questions about their distinct metabolic roles. 

PMID- 24874101
TI  - Molecular motor transport through hollow nanowires.
AB  - Biomolecular motors offer self-propelled, directed transport in designed
      microscale networks and can potentially replace pump-driven nanofluidics.
      However, in existing systems, transportation is limited to the two-dimensional
      plane. Here we demonstrate fully one-dimensional (1D) myosin-driven motion of
      fluorescent probes (actin filaments) through 80 nm wide, Al2O3 hollow nanowires
      of micrometer length. The motor-driven transport is orders of magnitude faster
      than would be possible by passive diffusion. The system represents a necessary
      element for advanced devices based on gliding assays, for example, in lab-on-a
      chip systems with channel crossings and in pumpless nanosyringes. It may also
      serve as a scaffold for bottom-up assembly of muscle proteins into ordered
      contractile units, mimicking the muscle sarcomere. 

PMID- 24874100
TI  - Prenatal expression patterns of genes associated with neuropsychiatric disorders.
AB  - OBJECTIVE: Neurodevelopmental disorders presumably involve events that occur
      during brain development. The authors hypothesized that neuropsychiatric
      disorders considered to be developmental in etiology are associated with
      susceptibility genes that are relatively upregulated during fetal life (i.e.,
      differentially expressed). METHOD: The authors investigated the presence of
      prenatal expression enrichment of susceptibility genes systematically, as
      composite gene sets associated with six neuropsychiatric disorders in the
      microarray-based "BrainCloud" dorsolateral prefrontal cortex transcriptome.
      RESULTS: Using a fetal/postnatal log2-fold change threshold of 0.5, genes
      associated with syndromic neurodevelopmental disorders (N=31 genes, p=3.37*10-3),
      intellectual disability (N=88 genes, p=5.53*10-3), and autism spectrum disorder
      (N=242 genes, p=3.45*10-4) were relatively enriched in prenatal transcript
      abundance, compared with the overall transcriptome. Genes associated with
      schizophrenia by genome-wide association studies were not preferentially fetally
      expressed (N=106 genes, p=0.46), nor were genes associated with schizophrenia by
      exome sequencing (N=212 genes, p=0.21), but specific genes within copy-number
      variant regions associated with schizophrenia were relatively enriched in
      prenatal transcript abundance, and genes associated with schizophrenia by meta
      analysis were functionally enriched for some neurodevelopmental processes. In
      contrast, genes associated with neurodegenerative disorders were significantly
      underexpressed during fetal life (N=46 genes, p=1.67*10-3). CONCLUSIONS: The
      authors found evidence for relative prenatal enrichment of putative
      susceptibility genes for syndromic neurodevelopmental disorders, intellectual
      disability, and autism spectrum disorder. Future transcriptome-level association
      studies should evaluate regions other than the dorsolateral prefrontal cortex, at
      other time points, and incorporate further RNA sequencing analyses.

PMID- 24874103
TI  - Re-characterization of an extrachromosomal circular plasmid in the pathogenic
      Leptospira interrogans serovar Lai strain 56601.
AB  - In China, Leptospira interrogans serovar Lai strain 56601 (str.56601) is one of
      main pathogenic strains that cause severe leptospirosis in both human and
      animals. The genome of this organism was completely sequenced in 2003. However,
      in 2011, we identified and corrected some assembly errors in the str.56601 genome
      due to the repeat sequences widely distributed in the Leptospira genome. In this
      study, we re-analyzed the previously reported mobile, phage-related genomic
      island in the chromosome and rectified detailed sequence information in both the
      plasmid and chromosome using various experimental methods. The presence of a
      separate circular extrachromosomal plasmid was also confirmed, and its location
      in the genomic region was determined relative to the genomic island reported in
      L. interrogans serovar Lai by a combination of pulsed-field gel electrophoresis 
      based and plasmid extraction-based Southern blot analysis. This report confirmed
      that the separate extrachromosomal circular plasmid is not integrated into the
      chromosome of L. interrogans str.56601 and markedly improved our understanding of
      the genomic organization, evolution, and pathogenesis of L. interrogans. In
      particular, characterization of this extrachromosomal circular plasmid will
      contribute to the development of genetic manipulation systems in pathogenic
      Leptospira species. 

PMID- 24874102
TI  - Evidence of horizontal transfer of non-autonomous Lep1 Helitrons facilitated by
      host-parasite interactions.
AB  - Horizontal transfer (HT) of transposable elements has been recognized to be a
      major force driving genomic variation and biological innovation of eukaryotic
      organisms. However, the mechanisms of HT in eukaryotes remain poorly appreciated.
      The non-autonomous Helitron family, Lep1, has been found to be widespread in
      lepidopteran species, and showed little interspecific sequence similarity of
      acquired sequences at 3' end, which makes Lep1 a good candidate for the study of
      HT. In this study, we describe the Lep1-like elements in multiple non
      lepidopteran species, including two aphids, Acyrthosiphon pisum and Aphis
      gossypii, two parasitoid wasps, Cotesia vestalis, and Copidosoma floridanum, one
      beetle, Anoplophora glabripennis, as well as two bracoviruses in parasitoid
      wasps, and one intracellular microsporidia parasite, Nosema bombycis. The patchy
      distribution and high sequence similarity of Lep1-like elements among distantly
      related lineages as well as incongruence of Lep1-like elements and host phylogeny
      suggest the occurrence of HT. Remarkably, the acquired sequences of both NbLep1
      from N. bombycis and CfLep1 from C. floridanum showed over 90% identity with
      their lepidopteran host Lep1. Thus, our study provides evidence of HT facilitated
      by host-parasite interactions. Furthermore, in the context of these data, we
      discuss the putative directions and vectors of HT of Lep1 Helitrons. 

PMID- 24874106
TI  - Thermal dose dependent optical property changes of ex vivo chicken breast tissues
      between 500 and 1100 nm.
AB  - This study examines the effectiveness of the thermal dose model in accurately
      predicting thermally induced optical property changes of ex vivo chicken breast
      between 500-1100 nm. The absorption coefficient, MUa, and the reduced scattering
      coefficient, MU's, of samples are measured as a function of thermal dose over the
      range 50  degrees C-70  degrees C. Additionally, the maximum observable changes
      in MUa and MU's are measured as a function of temperature in the range 50 
      degrees C-90  degrees C. Results show that the standard thermal dose model used
      in the majority of high-intensity focused ultrasound (HIFU) treatments is
      insufficient for modeling optical property changes, but that the isodose constant
      may be modified in order to better predict thermally induced changes.
      Additionally, results are presented that show a temperature dependence on changes
      in the two coefficients, with an apparent threshold effect occurring between 65 
      degrees C-70  degrees C.

PMID- 24874104
TI  - Balancing the interactions of ions, water, and DNA in the Drude polarizable force
      field.
AB  - Recently we presented a first-generation all-atom Drude polarizable force field
      for DNA based on the classical Drude oscillator model, focusing on optimization
      of key dihedral angles followed by extensive validation of the force field
      parameters. Presently, we describe the procedure for balancing the electrostatic
      interactions between ions, water, and DNA as required for development of the
      Drude force field for DNA. The proper balance of these interactions is shown to
      impact DNA stability and subtler conformational properties, including the
      conformational equilibrium between the BI and BII states, and the A and B forms
      of DNA. The parametrization efforts were simultaneously guided by gas-phase
      quantum mechanics (QM) data on small model compounds and condensed-phase
      experimental data on the hydration and osmotic properties of biologically
      relevant ions and their solutions, as well as theoretical predictions for ionic
      distribution around DNA oligomer. In addition, fine-tuning of the internal base
      parameters was performed to obtain the final DNA model. Notably, the Drude model
      is shown to more accurately reproduce counterion condensation theory predictions
      of DNA charge neutralization by the condensed ions as compared to the CHARMM36
      additive DNA force field, indicating an improved physical description of the
      forces dictating the ionic solvation of DNA due to the explicit treatment of
      electronic polarizability. In combination with the polarizable DNA force field,
      the availability of Drude polarizable parameters for proteins, lipids, and
      carbohydrates will allow for simulation studies of heterogeneous biological
      systems. 

PMID- 24874107
TI  - Clinical roundtable monograph: New data in emerging treatment options for
      chemotherapy-induced nausea and vomiting.
AB  - Chemotherapy-induced nausea and vomiting (CINV) has long been one of the most
      troublesome adverse effects of chemotherapy, leading to significant detriments in
      quality of life and functioning, increased economic costs, and, in some cases,
      the discontinuation of effective cancer therapy. The past 2 decades have
      witnessed a dramatic increase in the number of effective antiemetic agents, with
      the introduction of the serotonin (5-hydroxytryptamine [5-HT3]) receptor
      antagonists (ondansetron, granisetron, and palonosetron), the neurokinin-1 (NK1)
      receptor antagonists (aprepitant and fosaprepitant), and the identification of
      other agents that have demonstrated efficacy against CINV, including
      corticosteroids. These agents often provide excellent control of emesis. Nausea,
      however, has proven more intractable, particularly in the days after
      administration of chemotherapy. Newer antiemetic agents under study may provide
      additional CINV control, particularly against delayed nausea. New agents
      undergoing review by the US Food and Drug Administration for the prevention of
      CINV include the novel NK1 receptor antagonist rolapitant and a fixed-dose
      combination consisting of the novel NK1 receptor antagonist netupitant and
      palonosetron (NEPA). Adherence to clinical practice guidelines has been shown to
      significantly improve CINV control. As antiemetic therapy continues to evolve, it
      will be important for clinicians to stay informed of new developments and changes
      in guidelines.

PMID- 24874105
TI  - Interaction studies of the human and Arabidopsis thaliana Med25-ACID proteins
      with the herpes simplex virus VP16- and plant-specific Dreb2a transcription
      factors.
AB  - Mediator is an evolutionary conserved multi-protein complex present in all
      eukaryotes. It functions as a transcriptional co-regulator by conveying signals
      from activators and repressors to the RNA polymerase II transcription machinery.
      The Arabidopsis thaliana Med25 (aMed25) ACtivation Interaction Domain (ACID)
      interacts with the Dreb2a activator which is involved in plant stress response
      pathways, while Human Med25-ACID (hMed25) interacts with the herpes simplex virus
      VP16 activator. Despite low sequence similarity, hMed25-ACID also interacts with
      the plant-specific Dreb2a transcriptional activator protein. We have used GST
      pull-down-, surface plasmon resonance-, isothermal titration calorimetry and NMR
      chemical shift experiments to characterize interactions between Dreb2a and VP16,
      with the hMed25 and aMed25-ACIDs. We found that VP16 interacts with aMed25-ACID
      with similar affinity as with hMed25-ACID and that the binding surface on aMed25
      ACID overlaps with the binding site for Dreb2a. We also show that the Dreb2a
      interaction region in hMed25-ACID overlaps with the earlier reported VP16 binding
      site. In addition, we show that hMed25-ACID/Dreb2a and aMed25-ACID/Dreb2a display
      similar binding affinities but different binding energetics. Our results
      therefore indicate that interaction between transcriptional regulators and their
      target proteins in Mediator are less dependent on the primary sequences in the
      interaction domains but that these domains fold into similar structures upon
      interaction. 

PMID- 24874112
TI  - Novel functional variants locus in PLCE1 and susceptibility to digestive tract
      cancer in the Chinese population: a meta-analysis.
AB  - Three large-scale genome-wide association studies (GWAS) have identified a shared
      susceptibility variation phospholipase C epsilon 1 (PLCE1) rs2274223 for
      esophageal squamous cell carcinoma (ESCC) and/or gastric cardia adenocarcinomas
      (GCA) in the Chinese population. However, the association between PLCE1 rs2274223
      A>G and the risk of digestive tract cancer (DTC) has been inconsistent. We
      therefore carried out a meta-analysis of published case-control studies to derive
      a more precise estimation of the association between PLCE1 rs2274223 A>G and DTC
      risk. A comprehensive search was conducted to identify all eligible studies of
      PLCE1 rs2274223 polymorphism and DTC risk. Crude odds ratios (ORs) with 95%
      confidence intervals (95% CIs) were calculated to estimate the strength of
      associations in fixed or random effect models. Heterogeneity and publication bias
      were also assessed. A total of 15 case-control studies were identified, including
      29,805 cases and 32,225 controls. Overall, we found a statistically significant
      association between the PLCE1 rs2274223 polymorphism and DTC risk (G vs A:
      OR=1.29, 95% CI: 1.17-1.43; GA vs AA: OR=1.33, 95% CI: 1.18-1.51; GG vs AA:
      OR=1.71, 95% CI: 1.26-2.32; GG/GA vs AA: OR=1.33, 95% CI: 1.17-1.51), but the
      recessive model did not reach statistical significance (GG vs GA/AA: OR=0.94, 95%
      CI: 0.63-1.42). In the subgroup analysis by cancer types, we observed a
      significant risk for DTC in the ESCC and GCA subgroups. When stratified for
      source of controls, the results of the population-based subgroup analysis showed
      that the variant G allele might generally induce a significantly increased risk
      of DTC, except in hospital-based subgroups. In conclusion, PLCE1 rs2274223
      polymorphism may be used as a potential biomarker for DTC susceptibility
      particularly for ESCC and GCA in the Chinese population. 

PMID- 24874111
TI  - Differential expression of miRNAs with metabolic implications in hibernating
      thirteen-lined ground squirrels, Ictidomys tridecemlineatus.
AB  - Mammalian hibernators undergo significant physiological and biochemical changes
      when confronted with cold temperatures. Metabolic depression and translational
      repression are two examples of the various processes impacted during a torpor
      bout. MicroRNAs (miRNAs), non-coding transcripts that bind to mRNAs, are known
      regulators of mRNA translation and a growing number of these molecules have been
      found to be differentially expressed during hibernation. We hypothesized that a
      group of six miRNAs, with targets involved in various metabolic cascades, is
      modulated in selected tissues of the hibernating thirteen-lined ground squirrel
      Ictidomys tridecemlineatus. Expression levels of these miRNAs were assessed in
      the liver, heart, and skeletal muscle ground squirrel tissues using qRT-PCR. miR
      29a, miR-152, miR-195, miR-223, and miR-486 were shown to be up-regulated in the
      hibernating liver, while miR-378 was shown to be down-regulated in hibernating
      skeletal muscle tissue samples. Interestingly, fatty acid synthase (FAS), an
      enzyme involved in fatty acid biosynthesis and a miR-195 target, was shown to be
      down-regulated in hibernating squirrel liver. This data add to the growing
      signature of differentially expressed miRNAs during hibernation and puts the
      light on the potential regulation of fatty acid homeostasis by a miRNA in torpid
      animals. 

PMID- 24874114
TI  - Editorial comment: Symposium: femoral fractures: contemporary treatment
      approaches.

PMID- 24874113
TI  - Inferring host gene subnetworks involved in viral replication.
AB  - Systematic, genome-wide loss-of-function experiments can be used to identify host
      factors that directly or indirectly facilitate or inhibit the replication of a
      virus in a host cell. We present an approach that combines an integer linear
      program and a diffusion kernel method to infer the pathways through which those
      host factors modulate viral replication. The inputs to the method are a set of
      viral phenotypes observed in single-host-gene mutants and a background network
      consisting of a variety of host intracellular interactions. The output is an
      ensemble of subnetworks that provides a consistent explanation for the measured
      phenotypes, predicts which unassayed host factors modulate the virus, and
      predicts which host factors are the most direct interfaces with the virus. We
      infer host-virus interaction subnetworks using data from experiments screening
      the yeast genome for genes modulating the replication of two RNA viruses. Because
      a gold-standard network is unavailable, we assess the predicted subnetworks using
      both computational and qualitative analyses. We conduct a cross-validation
      experiment in which we predict whether held-aside test genes have an effect on
      viral replication. Our approach is able to make high-confidence predictions more
      accurately than several baselines, and about as well as the best baseline, which
      does not infer mechanistic pathways. We also examine two kinds of predictions
      made by our method: which host factors are nearest to a direct interaction with a
      viral component, and which unassayed host genes are likely to be involved in
      viral replication. Multiple predictions are supported by recent independent
      experimental data, or are components or functional partners of confirmed relevant
      complexes or pathways. Integer program code, background network data, and
      inferred host-virus subnetworks are available at
      http://www.biostat.wisc.edu/~craven/chasman_host_virus/. 

PMID- 24874115
TI  - Surgeons' attitudes are associated with reoperation and readmission rates.
AB  - BACKGROUND: Attitudes influence how people make decisions. In an effort to
      decrease pilot judgment-related accidents, the Federal Aviation Administration
      teaches new pilots about hazardous attitudes that are believed to be incompatible
      with safe flight: macho, impulsive, worry, resignation, self-confidence, and
      antiauthority. If these attitudes are hazardous for pilots and their passengers,
      they may also be incompatible with the reliable and safe delivery of surgical
      care. QUESTIONS/PURPOSES: The purposes of this study were (1) to ascertain to
      what extent surgeons harbor hazardous attitudes; and (2) to determine their
      relationship, if any, to reoperation and readmission rates. METHODS: We selected
      validated aviation psychology tools that are used to measure these attitudes in
      pilots. We converted the aviation scenarios to analogous situations for surgeons
      and invited all surgeons from one academic program to participate in this study.
      A total of 41 surgeons were eligible to participate; 37 (90%) completed the
      attitude prevalence protocol and 31 (76%) had complete reoperation and
      readmission data for the correlation and regression analysis. Attending
      orthopaedic surgeons completed the Modified Surgeon Hazardous Attitude Scale as
      well as a series of additional instruments. RESULTS: Levels of macho thought to
      be hazardous in pilots were present in nine (24%) surgeons. Similar, elevated
      levels of self-confidence were found in three (8%) surgeons. High levels of
      impulsivity were found in 5% (two surgeons) and high levels of antiauthority were
      found in 3% (one surgeon). Only one (3%) surgeon reported elevated levels of
      worry and no surgeon reported hazardous levels of resignation. Thirty percent (11
      surgeons) of surgeons harbored at least one elevated attitude level. In a
      regression model, macho attitude levels predicted 19% of the variation in
      surgeons' rate of readmissions and reoperations. CONCLUSIONS: High levels of
      hazardous attitudes may not be consistent with the routine delivery of safe
      surgical care in a teamwork setting where human factors and safe systems are the
      key to success. Further research is needed to determine if abnormally high levels
      of these hazardous attitudes impact patient care. LEVEL OF EVIDENCE: Level II,
      prognostic study. See Guidelines for Authors for a complete description of levels
      of evidence.

PMID- 24874117
TI  - Orthopaedic healthcare worldwide: the transparent pricing revolution in
      healthcare.

PMID- 24874119
TI  - Hearing their voices: The lived experience of recovery from first-episode
      psychosis in schizophrenia in South Africa.
AB  - BACKGROUND: Recovery was previously regarded as a somewhat unattainable goal, and
      the subjective experience was de-emphasised. Lately, the person and his or her
      experiences are emphasised. MATERIAL: Seven participants were interviewed
      regarding their experience of recovery from first-episode psychosis in
      schizophrenia. Data were analysed using interpretative phenomenological analysis
      (IPA). DISCUSSION: Support and having to care for another are possibly the
      greatest contributors to their recovery. Spirituality plays an important role.
      Stigma, found to be ingrained and pervasive, could be a barrier to recovery. The
      rediscovery by the participants of their abilities (re)introduced a sense of
      agency. CONCLUSION: The narrative in the process of recovery is crucial.

PMID- 24874116
TI  - Survival of modern knee tumor megaprostheses: failures, functional results, and a
      comparative statistical analysis.
AB  - BACKGROUND: Modular megaprostheses are now the most common method of
      reconstruction after segmental resection of the long bones in the lower
      extremities. Previous studies reported variable outcome and failure rates after
      knee megaprosthetic reconstructions. QUESTIONS/PURPOSES: The objectives of this
      study were to analyze the results of a modular tumor prosthesis after resection
      of bone tumor around the knee with respect to (1) survivorship; (2) failure rate;
      (3) comparative survivorship against different sites of reconstructions and of
      primary and revision implants; and (4) functional results on the Musculoskeletal
      Tumor Society (MSTS) scoring system. METHODS: Between 2003 and 2010, 247 rotating
      hinge Global Modular Reconstruction System (GMRS) knee prostheses were implanted
      in our institute for malignant and aggressive benign tumors. During this time,
      that group represented 23% of the patients who had oncologic megaprosthesis
      reconstruction about the knee after resection of primary or metastatic bone
      tumors (247 of 1086 patients). In the other 77% of cases we used other types of
      oncologic prostheses. Before 2003 we used the older Howmedica Modular Resection
      System and Kotz Modular Femur/Tibia Replacement from 2003 we used mostly the GMRS
      but we continued to use the HMRS in some cases such as patients with poor
      prognoses, elderly patients, or metastatic patients. Sites included 187 distal
      femurs and 60 proximal tibias. Causes of megaprosthesis failure were classified
      according to Henderson et al. in five types: Type 1 (soft tissue failure), Type 2
      (aseptic loosening), Type 3 (structural failure), Type 4 (infection), and Type 5
      (tumor progression). Followup was at a minimum oncologic followup of 2 years
      (mean, 4 years; range, 2-8 years). Kaplan-Meier actuarial curves of implant
      survival to major failures were done. Functional results were analyzed according
      to the MSTS II system; 223 of the 247 were available for functional scoring
      (81%). RESULTS: At latest followup, among 175 treated patients for primary
      reconstruction, 117 are continuously disease-free, 26 have no evidence of disease
      after treatment of relapse, eight are alive with disease, and 24 died from
      disease. The overall failure rate of the megaprostheses in our series was 29.1%
      (72 of 247). Type 1 failure occurred in 8.5% (21 of 247) cases, Type 2 in 5.6%
      (14 of 247), Type 3 in 0%, Type 4 in 9.3% (23 of 247), and Type 5 in 5.6% (14 of
      247). Kaplan-Meier curve showed an overall implant survival rate for all types of
      failures of 70% at 4 years and 58% at 8 years. Prosthetic survivorship for
      revisions was 80% at 5 years and for primary reconstructions was 60% at 5 years
      (p = 0.013). Survivorship to infection was 95% at 5 years for revision patients
      and 84% at 5 years for primary patients (p = 0.475). The mean MSTS score was 84
      (25.2; range, 8-30) with no difference between sites of localization (24.7 in
      proximal tibia versus 25.4 in distal femur reconstruction; p = 0.306).
      CONCLUSIONS: Results at a minimum of 2 years with this modular prosthesis are
      satisfactory in terms of survivorship (both oncologic and reconstructive) and
      causes and rates of failure. Although these results seem comparable with other
      like implants, we will continue to follow this cohort, and we believe that
      comparative trials among the available megaprosthesis designs are called for.
      LEVEL OF EVIDENCE: Level IV, therapeutic study. See Guidelines for Authors for a
      complete description of levels of evidence.

PMID- 24874120
TI  - Phenylene-diimine-capped conjugate of lower rim 1,3-calix[4]arene as molecular
      receptor for Mg2+ via arm conformational changes followed by aggregation and
      mimicking the species by molecular mechanics.
AB  - A phenylene-diimine-capped conjugate of lower rim 1,3-calix[4]arene (L) was
      synthesized, characterized, and shown to selectively bind to Mg(2+) using its
      capped arms. This results in a selective recognition of Mg(2+) through eliciting
      fluorescence enhancement of ~70 fold with a detection limit of 40 +/- 5 ppb.
      However, in the presence of blood serum, the lowest detection limit is 209 +/- 10
      ppb (0.2 MUM). The binding of Mg(2+) to L is authenticated by absorption and (1)H
      NMR data. The Job's plot derived on the basis of the absorption data showed 1:1
      stoichiometry between the receptor and Mg(2+). The 1:1 species was further
      confirmed through ESI MS, that is, being supported by the isotope peak pattern
      authenticating the presence of Mg(2+) in the complex. The L binds Mg(2+)
      octahedrally using the tetradentate L(2-) and two additional acetic acid moieties
      by bringing conformational changes as studied on the basis of MM computations.
      The conformational changes that occur in the capped arms upon Mg(2+) binding were
      supported experimentally by NOESY. AFM and SEM studies showed that spherical
      particles of L are modified into flower and chain type aggregates upon
      complexation with Mg(2+), confirming the supramolecular behavior of the species
      formed. 

PMID- 24874122
TI  - GPs should be freed up to make more endoscopy referrals, cancer charity says.

PMID- 24874121
TI  - Increased tobacco and alcohol use among women with joint hypermobility: a way to
      cope with anxiety?
AB  - Joint hypermobility (JH) is a common trait of heritable disorders of the
      connective tissue which has been identified as a risk factor for anxiety states.
      Anxiety and other negative emotions lead some people to use tobacco and alcohol
      as a coping strategy. The purpose of this study was to examine JH in relation to
      the consumption of these psychoactive substances and the associated anxiety and
      coping strategies. A cross-sectional sample of 305 female college students
      completed self-administered questionnaires on JH, tobacco and alcohol use, state
      and trait anxiety, and coping strategies. The prevalence of JH in the final
      sample (N = 301) was 51.8 %. The percentage of smokers, smokers using tobacco to
      calm anxiety, at-risk drinkers, tobacco and alcohol users, and the number of
      standard drinks consumed per week were significantly higher among females with JH
      than among those without it. The percentage of participants with severe state
      anxiety was significantly higher in the JH group, as were the emotion-focused
      coping score. The results of the logistic regression analysis showed that the
      odds of being assessed with JH were greater in those who consume tobacco and
      alcohol. This study provides evidence that women with JH report higher levels of
      state anxiety than non-JH women and use emotion-focused coping (i.e., efforts to
      regulate affect) more than any other coping strategies to deal with stress. These
      factors may help explain the increase in tobacco and alcohol use observed in this
      population.

PMID- 24874123
TI  - Pulmonary rehabilitation: definition, concept, and history.
AB  - Pulmonary rehabilitation is a complex intervention for which it is difficult to
      craft a succinct yet inclusive definition. Pulmonary rehabilitation should be
      considered for all patients with chronic obstructive pulmonary disease (COPD) who
      remain symptomatic or have decreased functional status despite otherwise optimal
      medical management. The essential components of pulmonary rehabilitation are
      exercise training and self-management education, tailored to the needs of the
      individual patient and integrated into the course of the disease trajectory.
      Emerging data support a role for pulmonary rehabilitation in nontraditional
      contexts, such as during exacerbation in the non-COPD patient and in the home
      setting. 

PMID- 24874124
TI  - The systemic nature of chronic lung disease.
AB  - The systemic effects and comorbidities of chronic respiratory disease such as
      COPD contribute substantially to its burden. Symptoms in COPD do not solely arise
      from the degree of airflow obstruction as exercise limitation is compounded by
      the specific secondary manifestations of the disease including skeletal muscle
      impairment, osteoporosis, mood disturbance, anemia, and hormonal imbalance.
      Pulmonary rehabilitation targets the systemic manifestations of COPD, the causes
      of which include inactivity, systemic inflammation, hypoxia and corticosteroid
      treatment. Comorbidities are common, including cardiac disease, obesity, and
      metabolic syndrome and should not preclude pulmonary rehabilitation as they may
      also benefit from similar approaches. 

PMID- 24874125
TI  - Evidence-based outcomes from pulmonary rehabilitation in the chronic obstructive
      pulmonary disease patient.
AB  - The aim of this article is to appraise the quality of evidence reported for
      important outcomes in pulmonary rehabilitation using the approach of the Grading
      of Recommendations Assessment, Development and Evaluation Working Group. This
      appraisal was carried out by identifying Cochrane systematic reviews and
      systematic reviews that have been subsequently reported since the last Cochrane
      report. The focus of this appraisal was to determine the effectiveness of
      pulmonary rehabilitation programs versus control therapy in chronic obstructive
      pulmonary disease patients. This analysis did not evaluate other aspects of the
      pulmonary rehabilitation intervention. 

PMID- 24874126
TI  - Pulmonary rehabilitation: timing, location, and duration.
AB  - Pulmonary rehabilitation programs vary in terms of duration and location.
      Differences also exists in the patients who are judged eligible for
      rehabilitation. This article reviews the options clinicians have to organize
      programs in terms of who should be referred, when, where, and for how long. There
      are several risk factors for lack of uptake and non-adherence to programs.
      Logistical aspects are also an important barrier. In terms of election, patients
      with muscle dysfunction are likely the best candidates for exercise training.
      Patients with exercise-induced symptoms and those after exacerbations should also
      be referred. 

PMID- 24874127
TI  - Exercise training in pulmonary rehabilitation.
AB  - Exercise training remains a cornerstone of pulmonary rehabilitation (PR) in
      patients with chronic respiratory disease. The choice of type of exercise
      training depends on the physiologic requirements and goals of the individual
      patient as well as the available equipment at the PR center. Current evidence
      suggests that, at ground walking exercise training, Nordic walking exercise
      training, resistance training, water-based exercise training, tai chi, and
      nonlinear periodized exercise are all feasible and effective in (subgroups) of
      patients with chronic obstructive pulmonary disease. In turn, these exercise
      training modalities can be considered as part of a comprehensive,
      interdisciplinary PR program. 

PMID- 24874128
TI  - Strategies to enhance the benefits of exercise training in the respiratory
      patient.
AB  - Despite the well-established benefits of exercise training in people with chronic
      respiratory disease, there are a group of people in whom it confers minimal
      gains. Furthermore, there is increasing recognition of the prevalence of comorbid
      conditions among people with chronic obstructive pulmonary disease and other
      respiratory diseases, such as musculoskeletal disorders, which make participation
      in traditional exercise training programs challenging. This article focuses on
      several adjuncts or strategies that may be implemented by clinicians during
      exercise training, with the goal of optimizing the proportion of pulmonary
      rehabilitation participants who achieve significant and meaningful gains on
      program completion. 

PMID- 24874130
TI  - Approaches to outcome assessment in pulmonary rehabilitation.
AB  - A comprehensive assessment is the foundation of a successful pulmonary
      rehabilitation programme. There is a broad selection of outcome measures that
      tend to be categorized into measures of exercise performance (including measures
      of strength) quality of life (health status), psychological well-being,
      nutritional status and more recently knowledge and self-efficacy. There is a
      growing interest in the measurement of physical activity too, although this is a
      current line of research activity. A sophisticated suite of outcomes allows the
      rehabilitation program to be personalised to the individual and deliver effective
      rehabilitation. 

PMID- 24874129
TI  - Collaborative self-management and behavioral change.
AB  - Behavioral change is critical for improving health outcomes in patients with
      chronic obstructive pulmonary disease. An educational approach alone is
      insufficient; changes in behavior, especially the acquisition of self-care
      skills, are also required. There is mounting evidence that embedding
      collaborative self-management (CSM) within existing health care systems provides
      an effective model to meet these needs. CSM should be integrated with pulmonary
      rehabilitation programs, one of the main goals of which is to induce long-term
      changes in behavior. More research is needed to evaluate the effectiveness of
      assimilating CSM into primary care, patient-centered medical homes, and
      palliative care teams. 

PMID- 24874131
TI  - Promoting regular physical activity in pulmonary rehabilitation.
AB  - Patients with chronic respiratory diseases are usually physically inactive, which
      is an important negative prognostic factor. Therefore, promoting regular physical
      activity is of key importance in reducing morbidity and mortality and improving
      the quality of life in this population. A current challenge to pulmonary
      rehabilitation is the need to develop strategies that induce or facilitate the
      enhancement of daily levels of physical activity. Because exercise training
      alone, despite improving exercise capacity, does not consistently generate
      similar improvements in physical activity in daily life, there is also a need to
      develop behavioral interventions that help to promote activity. 

PMID- 24874132
TI  - Pulmonary rehabilitation for respiratory disorders other than chronic obstructive
      pulmonary disease.
AB  - Pulmonary rehabilitation (PR) is an important therapeutic intervention that
      should no longer be considered suitable only for patients with chronic
      obstructive pulmonary disease (COPD). A strong rationale exists for providing PR
      to persons with a broad range of respiratory disorders other than COPD. Evidence
      shows that PR for these patients is feasible, safe and effective. A disease
      relevant approach should be undertaken, based on individual patients' needs.
      Further research is needed to better understand the optimal program content,
      duration and outcomes measures, to enable diverse patients to achieve maximal
      benefits of PR. 

PMID- 24874133
TI  - Pulmonary rehabilitation at the time of the COPD exacerbation.
AB  - Pulmonary rehabilitation (PR) is associated with improvements in exercise
      capacity, health related quality of life, psychological symptoms and response to
      utilization. Acute exacerbations threaten these improvements. An awareness of the
      clinical sequelae of acute exacerbation of chronic obstructive pulmonary disease
      enables approaches, such as early post exacerbation rehabilitation to mitigate
      its negative effects. 

PMID- 24874134
TI  - Anxiety, depression, and cognitive impairment in patients with chronic
      respiratory disease.
AB  - In this article, the prevalence of depression, anxiety, and cognitive impairment
      in persons with chronic obstructive pulmonary disease, and the impact of these
      psychological and cognitive factors on clinical outcomes in COPD is reviewed.
      Methods for screening and identification of these conditions in COPD are
      described. The extent to which depression, anxiety or cognitive impairment limit
      or modify the effectiveness of pulmonary rehabilitation, and whether pulmonary
      rehabilitation may ameliorate these psychological and cognitive impairments are
      discussed. 

PMID- 24874135
TI  - Palliative care and pulmonary rehabilitation.
AB  - Numerous barriers exist to the timely introduction of palliative care in patients
      with advanced chronic obstructive pulmonary disease (COPD). The complex needs of
      patients with advanced COPD require the integration of curative-restorative care
      and palliative care. Palliative care and pulmonary rehabilitation are both
      important components of integrated care for patients with chronic respiratory
      diseases. Pulmonary rehabilitation provides the opportunity to introduce
      palliative care by implementing education about advance care planning. Education
      about advance care planning addresses the information needs of patients and can
      be an effective strategy to promote patient-physician discussion about these
      issues. 

PMID- 24874136
TI  - Program organization in pulmonary rehabilitation.
AB  - Variable aspects of pulmonary rehabilitation (PR) programs include staff
      composition, setting, structure, and duration. Longer PR programs generally
      translate into greater improvements in outcomes and (perhaps) prolonged
      maintenance of benefits. Barriers to PR include transportation issues,
      inconvenience for the patient, cost and insurance coverage problems, lack of
      perceived benefit, concurrent illness, and influence of the provider. PR settings
      include inpatient and outpatient environments. PR has been shown to improve
      health care utilization during or immediately following chronic obstructive
      pulmonary disease exacerbations. Challenges to providing PR may be partially
      addressed by technological developments. 

PMID- 24874137
TI  - Promoting long-term benefits of pulmonary rehabilitation: the role of reducing
      the impact of respiratory exacerbations.
AB  - The importance of exercise for pulmonary patients is unquestioned. Decreased
      functional status has been attributed to increased hospitalizations, leading to
      further decreases in functionality, decreased quality of life and increased
      mortality. Despite known benefits of pulmonary rehabilitation, recruitment and
      retention of program participants can be a challenge. Alternatives to traditional
      pulmonary rehabilitation are reviewed with an emphasis on physical activity,
      exacerbation awareness and a reduction in hospital admissions. 

PMID- 24874138
TI  - Pulmonary rehabilitation: future directions.
AB  - Pulmonary rehabilitation is now an established standard of care for patients with
      chronic obstructive pulmonary disease (COPD). Although pulmonary rehabilitation
      has no appreciable direct effect on static measurements of lung function, it
      arguably provides the greatest benefit of any available therapy across multiple
      outcome areas important to the patient with respiratory disease, including
      dyspnea, exercise performance, and health-related quality of life. It also
      appears to be a potent intervention that reduces COPD hospitalizations,
      especially when given in the periexacerbation period. The role of pulmonary
      rehabilitation within the larger schema of integrated care represents a fruitful
      area for further research. 

PMID- 24874139
TI  - Preface.

PMID- 24874140
TI  - Effects of neonatal capsaicin treatment on thiamine monophosphatase (TMPase)
      activity in the substantia gelatinosa of the rat spinal cord.
AB  - The present study investigated changes in gelatinosal TMPase activity following
      capsaicin treatment. The gelatinosal TMPase activity was positive around
      postnatal day 3, and the activity disappeared when newborn rats were treated with
      capsaicin on postnatal days 2 or 3. The absence of TMPase activity was still
      observed four months after treatment. The possibility that TMPase is associated
      with nociception has to be considered. 

PMID- 24874141
TI  - A genetic taxonomy of hyperkinesis in the dog.
AB  - Among children who have difficulty inhibiting gross motor activity and focusing
      on learning tasks requiring them to do this, some are helped by central nervous
      system stimulants such as amphetamine, while others with identical symptoms are
      not. Similar variations in response to pharmacological agents are seen in other
      syndromes, suggesting that multiple biological mechanisms are involved and that
      these are selectively responsive to pharmacological manipulations. Diagnosis,
      therefore, involves not only the identification of the condition, but knowledge
      of the mechanisms by means of which it can be brought about, as well as some
      means of identify ing these. Since such variations often have a genetic basis,
      their identification and characterization by genetic and pharmacogenetic
      approaches permit the investigator to avoid confounding biological variation with
      statistical error and, ultimately, to suit the treatment to the mechanism when
      there is no final common path permitting a single intervention specific to a
      given syndrome. Because such researches are difficult with human patients, we
      have been attempting to identify animal models with analogous symptoms to human
      conditions and homologous mechanisms underlying these. The present paper is one
      in a series describing a dog model for hyperkinesis. 

PMID- 24874142
TI  - A pharmacologic investigation of the 'transport response' in the white rat.
AB  - In a series of six experiments, the ability of specific neurotransmitter
      antagonists to alter the 'transport response' was investigated in 19-day-old rat
      pups. The serotonergic blocker, methysergide, and the cholinergic blocker,
      scopolamine, did not produce any consistent changes in the intensity of the
      response. Likewise, the opiate receptor blocker, naloxone, was without effect.
      Large, dose-dependent decreases in transport response intensity were seen with
      administration of the beta-noradrenergic receptor blocker, propranolol, and with
      administration of the dopaminergic blocker, haloperidol. The alphanoradrenergic
      receptor blocker, phentolamine, produced inconsistent changes in the response.
      These results indicate a central catecholaminergic involvement in the transport
      response. 

PMID- 24874143
TI  - Myelinogenic cycle and myelination status of the brain of the catfish,
      Heteropneustes fossilis.
AB  - The lipid composition of the brain of the catfish, Heteropneustes fossilis
      (Bloch) was studied over the age period of 2-12 months, during which time the
      body weight increased from 2.5 to 33 g. The brain weight increased from 28 to 84
      mg between 2 and 9 months of age, with a further increase of only 7 mg during the
      following three months. The concentration of cholesterol increased slowly up to 5
      months of age, from which time the concentration began to increase rapidly and
      attained adult values at 8 months. The concentration of total lipid-P increased
      steadily up to the age of 7 months and remained almost constant thereafter. In
      contrast, there was very little increase in the concentration of the
      galactolipids (cerebroside + sulphatide) until month 5, after which the
      concentration increased rapidly to reach the adult level at 8 months of age. The
      concentration of cholesterol esters decreased during development; however, there
      occurred a transient rise at 5 months of age, which continued up to 8 months.
      These data indicate that the period between months 5 and 8 is one of active
      myelination in the brain of this species. The mole ratio of cholesterol,
      phospholipids, and galactolipids in the adult fish brain was 31:53:1, much higher
      than that in adult mammalian brain. Moreover, within the phospholipids,
      ethanolamine phosphoglyceride comprised < 10%, as against the corresponding value
      in the mammals of about 40%. These data therefore suggest a low level of
      myelination in the brain of catfish, as compared to that in higher species. 

PMID- 24874144
TI  - Thyroid hormone dependency of the developing dorsal raphe nucleus but not the
      superior cervical ganglion. Evidence from intraocular grafting experiments.
AB  - Immature superior cervical ganglia and brain stem pieces containing 5
      hydroxytryptamine neurons of the dorsal raphe nucleus were grafted to the
      anterior eye chamber of intact and thyroidectomized recipients. The grafts were
      left in the eye to mature for 4-6 weeks and were measured through the translucent
      cornea repeatedly to follow survival and growth. Monoaminergic nerve fibre
      outgrowth from the grafts onto the host irides was evaluated with Falck-Hillarp
      monoamine histochemistry on iris whole mounts. Body weight and plasma
      concentrations of thyroid-stimulating hormone monitored the thyroid state of both
      experimental and control animals. Intraocular survival and growth of immature
      superior cervical ganglia was not influenced by thyroid hormone deficiency,
      whereas the size of dorsal raphe nucleus grafts significantly increased during
      similar conditions. This increased size was entirely counteracted by daily
      substitution with l-thyroxine (100 MUg/kg, s.c.) to the thyroid deficient host
      animals. Fluorescence microscopy, including semiquantitative estimations of fibre
      outgrowth area and axon bundle formation in the irides, revealed no effects of
      the thyroid hormone deficiency on the peripheral superior cervical ganglia. The
      outgrowth of 5-hydroxytryptamine-containing nerve fibres from the brain stem
      grafts, on the other hand, showed a 50% decrease in both axon bundle formation
      and fibre outgrowth area in thyroidectomized hosts. This effect of the
      thyroidectomy could be completely reversed by daily substitution with l
      thyroxine. These data strongly support earlier reports describing a thyroid
      hormone dependency for central noradrenaline- and dopamine-containing neurons
      during similar conditions. Furthermore, the results indicate a role of thyroid
      hormones for nerve fibre growth during development of intraocularly isolated
      central but not peripheral monoaminergic neurons. 

PMID- 24874145
TI  - Behavioral effects of phosphatidylserine after perinatal administration in rats.
AB  - Behavioral effects of the acidic phospholipid phosphatidylserine (PS) were
      studied in rats after perinatal (prenatal or neonatal) administration. PS was
      administered to pregnant rats from day 5 of pregnancy. PS liposomes were also
      injected i.p. to offspring from postnatal days 1-5. PS-treated rats showed a more
      precocious onset of neonatal behaviors, and a significant improvement in
      acquiring avoidance responses when tested at 60 days of age. Behavioral effects
      of PS may be related to a possible influence on dendritic arborization during
      perinatal period. 

PMID- 24874146
TI  - Chemically defined medium for rat astroglial cells in primary culture.
AB  - We have developed a serum-free defined medium that supports the growth in primary
      culture of rat astroglial cells. Cells dissociated from cerebral hemispheres of
      newborn rats were maintained for 4 days in a basal medium (Waymouth's medium)
      containing 10% fetal calf serum, which was substituted by a serum-free medium.
      The basal medium was supplemented with insulin (5 MUg/ml) and fatty acid free
      bovine serum albumin (0.5 mg/ml). Under these conditions the cells proliferate as
      estimated by cell counts and DNA content; however, growth was less than in
      Waymouth's medium supplemented with 10% fetal calf serum. In contrast, a very
      similar morphology was observed between cultures grown in the serum-free or serum
      containing media. The serum-free medium allows some maturation of the astroglial
      cells as shown by the presence of glial fibrillary acidic (GFA) protein, S-100
      protein and glutamine synthetase (GS) activity. The astroglial cells can survive
      and grow in this chemically defined medium for up to 5 weeks. The ability to
      culture astroglial cells in such a minimal defined medium should facilitate
      investigations concerning the effects of growth factors on their proliferation
      and maturation. 

PMID- 24874147
TI  - First appearance of laminin in peripheral nerve, cerebral blood vessels and
      skeletal muscle of the rat embryo Immunofluorescence study with laminin and
      neurofilament antisera.
AB  - The formation of basal laminae in peripheral nerve was studied by
      immunofluorescence with laminin antisera in the rat embryo. Peripheral nerves
      were identified with neurofilament antisera in double labeled sections. In the
      adult rat perineurium and endoneurium were uniformly decorated by the antisera.
      Sensory neurons in posterior root ganglia were surrounded by a laminin positive
      basal lamina. Laminin immunoreactivity was first observed in posterior spinal
      roots on day 14. Anterior spinal roots and peripheral nerves remained laminin
      negative until day 17. The adult pattern (uniform decoration of endoneurium in
      large and small nerve trunks) was only observed on day 21. The formation of a
      basal lamina surrounding posterior root ganglion neurons was still not completed
      in 3-day-old rats. The only laminin positive structures in the brain and spinal
      cord were the external basal laminae and the blood vessels. The external basal
      lamina was present at all stages of development. In the spinal cord and brain
      stem vascular basal laminae were first identified with laminin antisera on day
      14, in the diencephalon and telencephalon on day 15. Laminin immunoreactivity in
      the basal laminae surrounding myotubes was first observed on day 16. 

PMID- 24874148
TI  - Astrocytes grown in oculo: Expression of cell morphologies on the iris as
      revealed by GFA immunohistochemistry.
AB  - Using two experimental approaches, the morphology of central astrocytes growing
      in vivo with the iris as a substratum were studied. When irides with mature
      intraocular grafts of cortex cerebri or locus coeruleus were stretch-prepared as
      whole mounts and processed for immunohistochemistry with antiserum against glial
      fibrillary acidic protein (GFA), a restricted halo of fluorescent cells and
      fibers was seen surrounding the grafts. Similarly, injection into the anterior
      eye chamber of adult rats, of a cell suspension prepared from cortex cerebri of
      10-day-old rat pups gave rise to both multiple GFA-positive astrocytic islets of
      different sizes and cell densities as well as scattered individual cells on the
      anterior surface of the host iris. In contrast, astrocytes from similar cell
      suspensions prepared from young adult animals survived very poorly. In both types
      of experiments, a large variation in cell morphology ranging from immature
      epitheloid, via large flat cells with few thick processes, to typical mature star
      shaped astrocytes was observed. This morphological variation is in agreement with
      that reported for similar cells in tissue culture. Immature-looking cells always
      had a strong perinuclear fluorescence; an inverse correlation was observed
      between cell body size and development of cell processes. Likewise, the
      fluorescence intensity was higher in well-developed cells as compared to more
      immature ones. The morphology of individual cells did not seem to be dependent
      upon the time in oculo, since no difference was observed between GFA-positive
      cells on irides examined 10 days and 6 weeks after injection of a cell
      suspension. Similarly, a high number of immature-looking cells was seen in irides
      with locus coeruleus transplants grafted more than 6 months earlier. Instead, the
      cell density seemed to be the crucial factor. Thus, star-shaped, well-developed
      cells were seen growing singly or in less dense groups whereas denser areas
      contained mainly immature-looking cells. Astrocytic processes had a tendency to
      follow the course of already existing intrinsic GFA-positive bundles and fibers
      in the iris. However, exceptions to this were occasionally seen. The fluorescence
      intensity was clearly higher in astrocytes growing on the iris than in intrinsic
      GFA-positive structures, suggesting molecular differences between central and
      peripheral GFA-immunoreactive material. 

PMID- 24874149
TI  - Immunohistochemical analysis of the ontogeny of neuropeptide Y immunoreactive
      neurons in foetal rat brain.
AB  - The development of neuropeptide Y-like immunoreactive structures in the foetal
      rat brain was investigated by means of the indirect immunohistofluorescence
      technique. Neuropeptide Y-like immunoreactive cells and fibres first appeared on
      day 13 of gestation, in the solitary tract nucleus, lateral reticular nucleus and
      nucleus ambiguus in the medulla oblongata, and in the primordial inferior
      colliculus and deep mesencephalic nucleus. Thereafter, neuropeptide Y-like
      immunoreactive cells and fibres increased in number in many areas including the
      primary olfactory cortex, the frontoparietal, somatosensory cortex, caudate
      putamen, lateral hypothalamus, ventrolateral thalamus, amygdala and
      parafascicular nucleus. The maximum number of cells over the age range studied,
      namely day 12 of gestation to birth day, occurred at around day 21. On the day of
      birth, accordingly, there were significantly fewer neuropeptide Y-like
      immunoreactive cell bodies in a number of brain areas, the most striking deficit
      being in the ventrolateral thalamus. The present study demonstrates the very
      early appearance of neuropeptide Y-like immunoreactive structures during foetal
      brain development. The functional role of the peptide during this period remains,
      however, to be determined. 

PMID- 24874151
TI  - Inventory and assessment of foliar natural enemies of the soybean aphid
      (Hemiptera: Aphididae) in South Dakota.
AB  - Soybean aphid (Aphis glycines Matsumura) (Hemiptera: Aphididae) is a major pest
      of soybean in northern production regions of North America, and insecticides have
      been the primary management approach while alternative methods are developed.
      Knowledge of arthropod natural enemies and their impact on soybean aphid is
      critical for developing biological control as a management tool. Soybean is a
      major field crop in South Dakota, but information about its natural enemies and
      their impact on soybean aphid is lacking. Thus, this study was conducted in field
      plots in eastern South Dakota during July and August of 2004 and 2005 to
      characterize foliar-dwelling, arthropod natural enemies of soybean aphid, and it
      used exclusion techniques to determine impact of natural enemies and ants
      (Hymenoptera: Formicidae) on soybean aphid densities. In open field plots, weekly
      soybean aphid densities reached a plateau of several hundred aphids per plant in
      2004, and peaked at roughly 400 aphids per plant in 2005. Despite these
      densities, a relatively high frequency of aphid-infested plants lacked arthropod
      natural enemies. Lady beetles (Coleoptera: Coccinellidae) were most abundant,
      peaking at 90 and 52% of all natural enemies sampled in respective years, and
      Harmonia axyridis Pallas was the most abundant lady beetle. Green lacewings
      (Neuroptera: Chrysopidae) were abundant in 2005, due mainly to large numbers of
      their eggs. Abundances of arachnids and coccinellid larvae correlated with
      soybean aphid densities each year, and chrysopid egg abundance was correlated
      with aphid density in 2005. Three-week cage treatments of artificially infested
      soybean plants in 2004 showed that noncaged plants had fewer soybean aphids than
      caged plants, but abundance of soybean aphid did not differ among open cages and
      ones that provided partial or total exclusion of natural enemies. In 2005, plants
      within open cages had fewer soybean aphids than those within cages that excluded
      natural enemies, and aphid density on open-cage plants did not differ from that
      on noncaged plants and those accessible by small predators. In a separate 3-yr
      experiment, exclusion of ants from soybean plants did not lead to differences in
      soybean aphid density compared with ant-accessible plants. Overall, these results
      suggest that the soybean aphid natural enemy guild is unsaturated and could be
      enhanced to improve biological control of soybean aphid in South Dakota. 

PMID- 24874150
TI  - Adolescent and adult rat cortical protein kinase A display divergent responses to
      acute ethanol exposure.
AB  - Adolescent rats display reduced sensitivity to many dysphoria-related effects of
      alcohol (ethanol) including motor ataxia and sedative hypnosis, but the
      underlying neurobiological factors that contribute to these differences remain
      unknown. The cyclic adenosine monophosphate (cAMP)-dependent protein kinase A
      (PKA) pathway, particularly the type II regulatory subunit (RII), has been
      implicated in ethanol-induced molecular and behavioral responses in adults.
      Therefore, the current study examined cerebral cortical PKA in adolescent and
      adult ethanol responses. With the exception of early adolescence, PKA RIIalpha
      and RIIbeta subunit levels largely did not differ from adult levels in either
      whole cell lysate or P2 synaptosomal expression. However, following acute ethanol
      exposure, PKA RIIbeta P2 synaptosomal expression and activity were increased in
      adults, but not in adolescents. Behaviorally, intracerebroventricular
      administration of the PKA activator Sp-cAMP and inhibitor Rp-cAMP prior to
      ethanol administration increased adolescent sensitivity to the sedative-hypnotic
      effects of ethanol compared to controls. Sp-cAMP was ineffective in adults
      whereas Rp-cAMP suggestively reduced loss of righting reflex (LORR) with
      paralleled increases in blood ethanol concentrations. Overall, these data suggest
      that PKA activity modulates the sedative/hypnotic effects of ethanol and may
      potentially play a wider role in the differential ethanol responses observed
      between adolescents and adults. 

PMID- 24874152
TI  - Diversity of bacterial symbionts in populations of Sitobion miscanthi (Hemiptera:
      Aphididae) in China.
AB  - Aphids are a group of insects frequently associated with bacterial symbionts.
      Although Chinese aphids harbor a high level of species diversity, the
      associations between Chinese aphids and bacterial symbionts are less known. In
      this study, we uncovered the diversity of bacterial symbionts in a Chinese
      widespread aphid, Sitobion miscanthi (Takahashi). In this study, we detected the
      aphid obligate symbiont Buchnera aphidicola, and two secondary symbionts,
      Hamiltonella defensa and Regiella insecticola, with the diagnostic polymerase
      chain reaction method in S. miscanthi samples. In addition, symbiotic species of
      Acinetobacter, Aeromonas, Enterobacter, Pantoea, and Pseudomonas, and the family
      Enterobacteriaceae were also found. Geographically, sporadic occurrences were
      detected for H. defensa and R. insecticola. Moreover, the infection rates of them
      vary widely among the infected populations: H. defensa (5.26-95.2%) and R.
      insecticola (5.26-46.7%). Phylogenetic analyses indicated that the strain of B.
      aphidicola mirrored the history and divergence of S. miscanthi; however, the H.
      defensa and R. insecticola strains were probably experienced horizontal
      transmission among S. miscanthi and its distantly related species. 

PMID- 24874153
TI  - The crypt-dwelling primary bacterial symbiont of the polyphagous pentatomid pest
      Halyomorpha halys (Hemiptera: Pentatomidae).
AB  - A recent invader of North America, the brown marmorated stink bug (Halyomorpha
      halys Stal) is a polyphagous pentatomid that harbors a gammaproteobacterial
      mutualist in the crypts of specialized midgut gastric caeca (region V4).
      Histological analyses revealed a single rod-shaped morphology abundant in distal
      V4 midgut caecal crypts. A strong fluorescence signal was detected when thin
      sections of these tissues were hybridized with a fluorescently-labeled,
      Enterobacteriaceae-specific oligonucleotide probe. A single operational taxonomic
      unit (OTU) assigned to the Pantoea genus represented >99% of 3,454 16S rDNA
      amplicons obtained from midgut V4 tissues and egg samples. Detection of H. halys
      primary symbiont in DNA extracted from eggs suggested vertical maternal
      inheritance as the mode of intergenerational transmission. Consistent detection
      of the bacterial symbiont in geographically distinct H. halys populations
      strongly supports an intimate association between these two organisms. An
      inferred phylogeny of gammaproteobacterial symbionts of pentatomids placed the
      Pantoea-assigned OTU from H. halys within a clade distinct from primary bacterial
      symbionts of related stink bugs, Nezara viridula (L.) and Eurydema rugosa
      Motschulsky. Given these data, Candidatus "Pantoea carbekii" is proposed as the
      name of the primary bacterial symbiont of H. halys. 

PMID- 24874154
TI  - Hypervirulent Diuraphis noxia (Hemiptera: Aphididae) biotype SAM avoids
      triggering defenses in its host (Triticum aestivum) (Poales: Poaceae) during
      feeding.
AB  - In the molecular arms race between aphids and plants, both organisms rely on
      adaptive strategies to outcompete their evolutionary rival. In the current study,
      we investigated the difference in elicited defense responses of wheat (Triticum
      aestivum L.) near-isogenic lines with different Dn resistance genes, upon feeding
      by an avirulent and hypervirulent Diuraphis noxia Kurdjumov biotype. After
      measuring the activity of a suite of enzymes associated with plant defense, it
      became apparent that the host does not recognize the invasion by the
      hypervirulent aphid because none of these were induced, while feeding by the
      avirulent biotype did result in induction of enzyme activity. Genomic plasticity
      in D. noxia may be a likely explanation for the observed differences in virulence
      between D. noxia biotype SA1 and SAM, as demonstrated in the current study. 

PMID- 24874155
TI  - Host settling behavior, reproductive performance, and effects on plant growth of
      an exotic cereal aphid, Metopolophium festucae subsp. cerealium (Hemiptera:
      Aphididae).
AB  - The cereal aphid Metopolophium festucae subsp. cerealium (Stroyan) is a recent
      addition to North America, but little is known about this species in its exotic
      habitat. We surveyed aphid populations for 3 years (2011-2013) to investigate
      changes in aphid density in the Pacific Northwest United States. We tested aphid
      host settling preference and fecundity on eight grass species, four native
      grasses (bluebunch wheatgrass, blue wild rye, Idaho fescue, and rough fescue) and
      four cereal crops (corn, wheat, barley, and oat), and evaluated the effects of
      aphid feeding on plant biomass. Four important findings emerged: 1) aphid
      prevalence in sweep net samples increased from 2011 to 2012, but remained stable
      from 2012 to 2013; 2) aphids preferentially settled on wheat and avoided corn,
      but aphids did not discriminate between barley, oat, and native grasses; 3) aphid
      fecundity was high on wheat and barley, intermediate on oat and blue wild rye,
      low on Idaho fescue, rough fescue, and bluebunch wheatgrass, and aphids did not
      reproduce at all on corn; and 4) barley, corn, oats, Idaho fescue, and blue wild
      rye were not susceptible to aphid feeding damage, but wheat, rough fescue, and
      bluebunch wheatgrass were susceptible to aphid feeding damage. Our results
      suggest that wheat and barley are preferred by M. festucae cerealium, and that
      aphids reproduce most rapidly on these hosts and cause significant reductions in
      wheat but not barley growth. Also, M. festucae cerealium appears capable of
      surviving on native grasses, although only bluebunch wheatgrass and rough fescue
      were susceptible to aphid feeding damage. 

PMID- 24874156
TI  - Within-tree and temporal distribution of Pezothrips kellyanus (Thysanoptera:
      Thripidae) nymphs in citrus canopies and their influence on premature fruit
      abscission.
AB  - Pezothrips kellyanus (Bagnall) (Thysanoptera: Thripidae) has recently become a
      pest of citrus whose nymphs feed on the surface of young fruitlets. This feeding
      habit causes patches or rings of tissue scar around the apex as fruit mature.
      Currently, little is known about the distribution of P. kellyanus nymphs. Further
      knowledge would allow the development of an appropriate sampling protocol and
      targeted pesticide application. In our first experiment, the abundance of first-
      and second-generation P. kellyanus nymphs was surveyed in a citrus orchard at
      different times of day to characterize their spatial and temporal distributions.
      The distribution of damaged fruit was also measured at harvest. Our results
      showed that P. kellyanus nymphs tended to be present in the upper half of the
      canopy and mainly damaged the fruit located in this area of the canopy. However,
      P. kellyanus nymphs were uniformly distributed among the four cardinal directions
      of the canopy and throughout the day. Consequently, cardinal direction and time
      of the day seem to be less important when developing a sampling plan or in
      improving targeting or timing of insecticidal spray applications. In our second
      experiment, we tracked the presence of P. kellyanus nymphs in labeled fruit
      daily. These data were used to determine how many days the nymphs occupied a
      fruit and to relate occupancy and premature fruit abscission. The nymphs of P.
      kellyanus remained on the same fruit for only 1 d. The rate of fruit abscission
      in June was significantly higher in fruit occupied by first-generation P.
      kellyanus nymphs than in nonoccupied fruit. 

PMID- 24874157
TI  - Patterns of flight behavior and capacity of unmated navel orangeworm
      (Lepidoptera: Pyralidae) adults related to age, gender, and wing size.
AB  - The navel orangeworm, Amyelois transitella (Walker) (Lepidoptera: Pyralidae), is
      a key pest of almond, pistachio, and walnut tree crops in California.
      Understanding dispersal of adults between orchards is important to improving
      management options. Laboratory flight behavior of unmated navel orangeworm of
      ages 1, 2, 3, 5, and 7 d posteclosion was examined using flight mills. As a
      group, females flew farther and longer than males, but the differences were not
      statistically significant. Flight speed did not differ between sexes. Flight
      duration and distance did not differ with age, except that 7-d-old adults
      performed worse for these parameters than did 1- and 2-d-old adults. Females
      began their flights ?1.5 h after the onset of dusk, and ?1.5 h earlier in the
      night than males. Flight capacity and propensity were substantial for both sexes
      and all age classes tested. At least 20% of adults (except 7-d-old males) made a
      continuous flight >=5.5 h, and median total distances flown during the 10.5-h
      night ranged from 7 to 15 km depending on age class. Thus navel orangeworm flight
      mill performance was greater than that of most pests tested from the families
      Pyralidae and Tortricidae. Surface area and length of forewings and hindwings
      were greater in females than males, but had little effect on flight performance.
      The results are generally consistent with field observations of navel orangeworm
      dispersal, but it will be important to characterize the effects of mating on
      flight, and flight on fecundity. 

PMID- 24874158
TI  - Predation of Anastrepha ludens (Diptera: Tephritidae) by Norops serranoi
      (Reptilia: Polychrotidae): functional response and evasion ability.
AB  - The Mexican fruit fly, Anastrepha ludens (Loew), is one of the 10 worldwide more
      important fruit crop pests. Orchards of southeastern Chiapas also shelter the
      tree-dwelling lizard Norops serranoi (Kohler), which likely prey upon these
      flies. In standard laboratory conditions, we determined the functional response
      of four male and four female lizards on mass-reared fruit flies. We used a
      general logistic analysis of proportion of killed prey versus available prey to
      determine the shape of the functional response. Male lizards showed a type II
      functional response, while females showed a type III functional response. For the
      highest fruit fly densities, female lizards caught significantly more fruit flies
      than males did. The predator evasion ability and the survival of mass-reared and
      wild fruit flies were compared. Wild fruit flies evaded more male lizard attacks
      than mass-reared flies. However, when female lizards attacked, there was no
      significant difference between strains. Fruit flies survival was higher with male
      than with female lizards, but it did not depend on fruit fly strains. This is the
      first report of a vertebrate preying on the Mexican fruit fly, demonstrating that
      female lizards impose a higher predation pressure and are more efficient at
      capturing wild fruit flies than males. We discuss the implications of our results
      on mass-rearing and quality control of sterile flies. 

PMID- 24874159
TI  - A comparison of spider communities in Bt and non-Bt rice fields.
AB  - To assess the potential adverse effects of a Bt rice line (Japonica rice
      cultivar, Nakdong) expressing a synthetic cry1Ac1 gene, C7-1-9-1-B, which was
      highly active against all larval stages of Cnaphalocrocis medinalis (Guenee)
      (Lepidoptera: Crambidae), we investigated the community structure of spiders in
      Bt and non-Bt rice fields during the rice-growing season in 2007 and 2008 in
      Chungcheongnam-do, Korea. Spiders were surveyed with a sweep net and suction
      device. Suction sampling captured more spiders, measured in terms of species
      level and abundance, than sweeping. Araneidae and Thomisidae were captured more
      by sweeping, and certain species were captured only by sweeping. These findings
      show that both suction and sweep sampling methods should be used because these
      methods are most likely complementary. In total, 29 species in 23 genera and nine
      families were identified from the 4,937 spiders collected, and both Bt and non-Bt
      rice fields showed a typical Korean spider assemblage. The temporal patterns of
      spider species richness and spider abundance were very similar between Bt and non
      Bt rice, although significant differences in species richness were observed on a
      few occasions. Overall, spider community structure, including diversity, the
      dominant species, and abundance did not differ between Bt and non-Bt rice. The
      results of the study indicated that the transgenic Cry1Ac rice lines tested in
      this study had no adverse effects on the spider community structure of the rice
      fields. 

PMID- 24874160
TI  - Carbon isotope ratios document that the elytra of western corn rootworm
      (Coleoptera: Chrysomelidae) reflects adult versus larval feeding and later instar
      larvae prefer Bt corn to alternate hosts.
AB  - In much of the Corn Belt and parts of Europe, the western corn rootworm,
      Diabrotica virgifera virgifera LeConte, is the most important insect pest of
      maize. The need for additional basic knowledge of this pest has been highlighted
      while developing resistance management plans for insecticidal genetically
      modified crops. This study evaluated the possibility of tracking feeding habits
      of western corn rootworm larvae using stable carbon isotope signatures. Plants
      accumulate different ratios of (13)C:(12)C isotopes, usually expressed as
      delta(13)C, according to whether they use the C3 or C4 photosynthetic pathway.
      Herbivore biomass is expected to reflect the delta(13)C of the food they eat. For
      the current experiment, western corn rootworm larvae were grown on different
      species of plants exhibiting different delta(13)C values. The delta(13)C values
      were then measured in elytra of emerged beetles. When beetles were unfed, biomass
      reflected larval feeding. When beetles were fed for 31 d postemergence,
      delta(13)C values of elytra almost exclusively reflected adult feeding. These
      results suggest the use of caution in the interpretation of delta(13)C data
      aiming to document larval diet history when adult feeding history is unknown. The
      technique was also used to evaluate western corn rootworm larval choice between
      alternate hosts and maize with and without genetically modified (Bt) traits aimed
      at their control. Propensity for feeding on alternate hosts versus maize was
      biased toward feeding on maize regardless whether the maize had Bt or not,
      suggesting western corn rootworm larvae were not repelled by Bt. These data will
      be helpful for regulators in interpreting western corn rootworm feeding data on
      Bt maize. 

PMID- 24874161
TI  - Predictors of postoperative complications in elderly and oldest old patients with
      gastric cancer.
AB  - BACKGROUND: The incidence of gastric cancer has been increasing among elderly
      persons in Japan. This study aimed to clarify risk factors for postoperative
      complications in oldest old patients with gastric cancer. METHODS: One-hundred
      ninety patients more than 75 years old with gastric cancer underwent gastrectomy
      between 2000 and 2011. Patients were classified into two groups: group A included
      29 patients who were 85 years or older (oldest old patients), and group B
      included 161 patients who were 75-84 years of age. Perioperative parameters
      associated with complications were compared in each group. RESULTS: The
      preoperative estimated glomerular filtration rate was significantly lower in
      group A (p = 0.03). The two groups significantly differed in performance status
      (p = 0.018). Patients in group A received a lesser extent of lymph node
      dissection and had fewer lymph nodes excised. As a result, the duration of the
      operation was significantly shorter in group A. There were no significant
      differences in the frequency or grade of total complications or mortality between
      the two groups. Operative hemorrhage (>300 ml) and Hiroshima POSSUM (predicted
      morbidity risk >40) were risk factors in both groups A and B; the risk factors of
      preoperative serum albumin level and prognostic nutritional index (PNI) were
      specific to group A. CONCLUSIONS: Adjustments to the extent of surgery among
      oldest old patients most likely reduces the incidence of postoperative
      complications in this group. Preoperative serum albumin level and PNI are
      significant predictors of postoperative complications in oldest old patients with
      gastric cancer.

PMID- 24874162
TI  - Comparison of the use of downstream tests after exercise treadmill testing by
      cardiologists versus noncardiologists.
AB  - Although exercise treadmill testing (ETT) is a useful initial test for patients
      with suspected cardiovascular (CV) disease, there is concern regarding the use of
      downstream imaging tests especially in the setting of equivocal or positive ETTs.
      Patients with no history of coronary artery disease who underwent ETT between
      2009 and 2010 were prospectively included. Referring physicians were categorized
      as cardiologists and noncardiologists. Downstream tests included nuclear
      perfusion imaging, coronary computed tomography angiography, stress
      echocardiography, stress magnetic resonance, and invasive coronary angiography
      performed up to 6 months after the ETT. Patients were followed for CV death,
      myocardial infarction, and coronary revascularization for a median of 2.7 years.
      Among 3,656 patients, the ETT were negative in 2,876 (79%), positive in 132
      (3.6%), and inconclusive in 643 (18%). Cardiologists ordered less downstream
      tests than noncardiologists (9.5% vs 12.2%, p=0.02), with less noninvasive tests
      (5.9% vs 10.4%, p<0.0001) and more invasive angiography (3.6% vs 1.8%, p<0.0001).
      After adjustment for confounding, patients evaluated by cardiologists were less
      likely to undergo additional testing after equivocal (odds ratio: 0.65, p=0.02)
      or positive ETT results (odds ratio: 0.39, p=0.02), whereas after negative ETT,
      the odds ratio was 1.7 (p=0.06). There was no difference in the rate of adverse
      CV events between patients referred by cardiologists versus noncardiologists. In
      conclusion, patients referred for ETT by cardiologists are less likely to undergo
      additional testing, particularly noninvasive tests, than those referred by
      noncardiologists. The lower rate of tests is driven by a lower rate of tests
      after positive or inconclusive ETT.

PMID- 24874163
TI  - Comparison of patients with peripartum heart failure and normal (>=55%) versus
      low (<45%) left ventricular ejection fractions.
AB  - The current definition of peripartum cardiomyopathy (PC) is restricted to
      patients with left ventricular systolic dysfunction (ejection fraction [EF]<45%).
      Data on peripartum heart failure (HF) with normal EF are sparse. We describe
      clinical characteristics of patients with normal (>=55%) and patients with low
      (<45%) left ventricular ejection fractions (LVEFs). Electronic medical records
      (2006 to 2013) of our tertiary care center were retrospectively screened to
      identify peripartum HF with normal EF, defined as an entity meeting Framingham
      criteria for HF with symptom onset during the last month of pregnancy or up to 5
      months after delivery and with an EF of >=55%. Clinical characteristics,
      echocardiographic parameters, and outcomes of these patients were compared with
      age-matched control patients with traditionally defined PC (EF<45%). A total of
      25 patients with PC and EF>=55% were identified. Exclusion of hypertension (n=9),
      preeclampsia (n=1), and diabetes mellitus (n=2) yielded 13 patients with PC and
      EF>=55%. Age-matched patients with traditional PC (EF<45%) constituted controls
      (n=16). Compared with patients with PC and low LVEF, patients with PC and normal
      LVEF had lower B-type natriuretic peptide levels, systolic and diastolic left
      ventricular dimensions, left atrial size, and incidence of decompensated HF
      during delivery (p<0.05). Compared with historical age-matched controls, patients
      with normal LVEF exhibited attenuated E' mitral annular velocities. On follow-up,
      these patients were associated with a lower New York Heart Association functional
      class. In conclusion, peripartum HF with normal LVEF appears to be a distinct
      entity.

PMID- 24874164
TI  - Brief report #1: engaging students in gerontological practice and research.
AB  - Caregivers Accessing Resources and Essential Services (CARES) is an innovative
      caregiver program that utilizes the "wraparound system of care" as its main
      intervention. The program is based on 10 core principles and conducted over a
      four-phase process. Undergraduate and graduate students gathered insight into the
      program's unique practice model by way of internships and shadowing the program's
      facilitators. Students are exposed to the unique needs of older caregivers who
      are disproportionately represented in the geographical area in which the program
      is located. In addition, students applied research concepts such as psychometric
      measures and treatment fidelity in evaluating the program. The program enhanced
      practice and research competencies along with knowledge of and sensitivity to
      older adult caregivers. 

PMID- 24874166
TI  - Reply: To PMID 24411521.

PMID- 24874167
TI  - Caution in interpretation of association of genetic variant with infectious
      disease outcomes.

PMID- 24874168
TI  - Asymmetric and symmetric dimethylarginine are associated with coronary artery
      lesions in Kawasaki disease.
AB  - OBJECTIVE: To determine whether 3 biomarkers, L-arginine, asymmetric
      dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA), can predict
      outcomes in patients with Kawasaki disease (KD). STUDY DESIGN: Plasma levels of L
      arginine, ADMA, and SDMA were measured in 39 patients with KD and 27 febrile
      control patients. RESULTS: Plasma L-arginine, ADMA, and SDMA levels were lower in
      patients with KD than in control patients before treatment with intravenous
      immunoglobulin (IVIG; P=.027, P<.001, and P<.001, respectively). After treatment
      with IVIG, L-arginine, ADMA, L-arginine/ADMA ratios, and arginine methylation
      ([ADMA+SDMA]/L-arginine) increased significantly (P<.001, P=.001, P=.014, and
      P=.001, respectively). Compared with control patients, persistent lower SDMA and
      higher ADMA/SDMA ratios existed in patients with KD. Furthermore, a lesser
      magnitude of change in terms of L-arginine and ADMA/SDMA ratios after IVIG
      treatment was associated with the formation of coronary dilation (P=.025, and
      .029, respectively). CONCLUSION: Levels of L-arginine, ADMA, and SDMA appear to
      be associated with KD. Lower L-arginine levels and ADMA/SDMA after treatment with
      IVIG was associated with coronary artery abnormalities patients with KD.

PMID- 24874172
TI  - The neurosteroid allopregnanolone impairs object memory and contextual fear
      memory in male C57BL/6J mice.
AB  - Allopregnanolone (ALLO, or 3alpha-hydroxy-5alpha-pregnan-20-one) is a steroid
      metabolite of progesterone and a potent endogenous positive allosteric modulator
      of GABA-A receptors. Systemic ALLO has been reported to impair spatial, but not
      nonspatial learning in the Morris water maze (MWM) and contextual memory in
      rodents. These cognitive effects suggest an influence of ALLO on hippocampal
      dependent memory, although the specific nature of the neurosteroid's effects on
      learning, memory or performance is unclear. The present studies aimed to
      determine: (i) the memory process(es) affected by systemic ALLO using a
      nonspatial object memory task; and (ii) whether ALLO affects object memory via an
      influence within the dorsal hippocampus. Male C57BL/6J mice received systemic
      ALLO either before or immediately after the sample session of a novel object
      recognition (NOR) task. Results demonstrated that systemic ALLO impaired the
      encoding and consolidation of object memory. A subsequent study revealed that
      bilateral microinfusion of ALLO into the CA1 region of dorsal hippocampus
      immediately following the NOR sample session also impaired object memory
      consolidation. In light of debate over the hippocampal-dependence of object
      recognition memory, we also tested systemic ALLO-treated mice on a contextual and
      cued fear-conditioning task. Systemic ALLO impaired the encoding of contextual
      memory when administered prior to the context pre-exposure session. Together,
      these results indicate that ALLO exhibits primary effects on memory encoding and
      consolidation, and extend previous findings by demonstrating a sensitivity of
      nonspatial memory to ALLO, likely by disrupting dorsal hippocampal function. 

PMID- 24874174
TI  - One-step synthesis of water-soluble hexagonal NaScF4:Yb/Er nanocrystals with
      intense red emission.
AB  - Water-soluble hexagonal NaScF4:Yb/Er nanocrystals have been directly synthesized
      via a facile one-step hydrothermal route. The as-prepared nanocrystals were
      monodisperse and could form stable colloidal solutions in polar solvents, such as
      water and ethanol. The novel NaScF4:Yb/Er nanocrystals exhibited intrinsic
      intense red upconversion emission, in contrast to other lanthanide-doped fluoride
      nanocrystals. Remarkably, the upconversion emission intensity was enhanced ~6.8
      times through the coating of an active-shell (containing Yb(3+)) surrounding the
      NaScF4:Yb/Er core nanocrystals, owing to surface passivation effect and efficient
      energy transfer from Yb(3+) ions in both the core and the shell to Er(3+) ions.
      These water-soluble hexagonal NaScF4:Yb/Er nanocrystals with intense red emission
      are ideal for a variety of in vitro and in vivo biological imaging applications. 

PMID- 24874176
TI  - Development and validation of the Attitudes to Pharmacist Services for Diabetes
      Scale (APSDS).
AB  - BACKGROUND: Community pharmacists are uniquely placed to deliver a range of
      services to support clients with type 2 diabetes (T2D). However successful uptake
      of new services depends on consumers' willingness to access these. An
      understanding of consumer perspectives is thus pivotal to designing appropriate
      services and to developing strategies to promote uptake. OBJECTIVES: To develop
      and validate a new measure the "Attitudes to Pharmacist Services for Diabetes
      Scale" (APSDS) and to assess consumers' interest in receiving diabetes services
      from community pharmacy. METHODS: The APSDS, based on Donabedian's model of
      service quality, comprised 14 items on a five-point scale from strongly disagree
      to strongly agree. A cross-sectional online and postal survey was conducted among
      T2D members of the Australian Diabetes Council between April and June 2013. The
      sample was randomly split into two groups. Construct validity was first examined
      with principal components analysis (PCA) and Rasch analysis on the first sample
      and confirmed with confirmatory factor analysis (CFA) and Rasch analysis on the
      second sample. Criterion validity was examined through correlation of APSDS
      scores with variables predicted a priori to correlate with consumer attitudes.
      Internal consistency was examined with Cronbach's alpha. RESULTS: 540 consumers
      completed the survey (57.6% male). PCA produced a two-component solution. The two
      sub-scales were labeled "Attitudes to pharmacy diabetes services" (6 items; alpha
      = 0.92) and "Attitudes to pharmacist competency in diabetes care" (4 items; alpha
      = 0.89). Fit of the data to the Rasch model was generally good. APSDS sub-scale
      scores were positively correlated with likelihood of using pharmacy service for
      diabetes (Spearman's rho = 0.30, 0.32). The CFA confirmed the two-component
      solution. CONCLUSION: The APSDS scales represent a valid and reliable tool which
      may serve to identify attitudes to pharmacists' diabetes services in different
      regions and communities as well as measure the impact of pharmacy diabetes
      interventions on consumer perspectives.

PMID- 24874173
TI  - Switching between forest and trees: opposite relationship of progesterone and
      testosterone to global-local processing.
AB  - Sex differences in attentional selection of global and local components of
      stimuli have been hypothesized to underlie sex differences in cognitive strategy
      choice. A Navon figure paradigm was employed in 32 men, 41 naturally cycling
      women (22 follicular, 19 luteal) and 19 users of oral contraceptives (OCs)
      containing first to third generation progestins in their active pill phase.
      Participants were first asked to detect targets at any level (divided attention)
      and then at either the global or the local level only (focused attention). In the
      focused attention condition, luteal women showed reduced global advantage (i.e.
      faster responses to global vs. local targets) compared to men, follicular women
      and OC users. Accordingly, global advantage during the focused attention
      condition related significantly positively to testosterone levels and
      significantly negatively to progesterone, but not estradiol levels in a multiple
      regression model including all naturally cycling women and men. Interference
      (i.e. delayed rejection of stimuli displaying targets at the non-attended level)
      was significantly enhanced in OC users as compared to naturally cycling women and
      related positively to testosterone levels in all naturally cycling women and men.
      Remarkably, when analyzed separately for each group, the relationship of
      testosterone to global advantage and interference was reversed in women during
      their luteal phase as opposed to men and women during their follicular phase. As
      global processing is lateralized to the right and local processing to the left
      hemisphere, we speculate that these effects stem from a testosterone-mediated
      enhancement of right-hemisphere functioning as well as progesterone-mediated
      inter-hemispheric decoupling. 

PMID- 24874178
TI  - An impedance-based flow microcytometer for single cell morphology discrimination.
AB  - Cell shape is a fundamental biological feature, providing specific information
      about physiological or pathological cellular conditions. Most of the state-of-the
      art microfluidic cytometers, however, only allow simple cell analysis, including
      viability studies, cell counting and sorting. In this work, we present a non
      invasive, label-free device capable of single cell morphology discrimination in
      continuous flow. The device is based on the principle of liquid electrodes,
      fabricated in a cross configuration around a sensing zone. This arrangement
      allows measurement of cell impedance along orthogonal orientations and extraction
      of an index describing cell shape anisotropy. By adding prior to the sensing
      volume a series of lateral liquid electrodes, the particle stream was focused
      toward the channel midline and each cell was oriented in a specific direction
      before shape sensing. We demonstrate the proof of concept by performing spherical
      and elongated particle discrimination. As an application, we show that the shape
      changes experienced during cell division can be monitored and characterized. In
      particular, budding yeasts at different stages of the mitotic cycle were
      identified by extracting their anisotropy index. 

PMID- 24874177
TI  - Multi-modal intervention improved oral intake in hospitalized patients. A one
      year follow-up study.
AB  - BACKGROUND: Good nutritional practice (GNP) includes screening, nutrition plan
      and monitoring, and is mandatory for targeted treatment of malnourished patients
      in hospital. AIMS: To optimize energy- and protein-intake in patients at
      nutritional risk and to improve GNP in a hospital setting. METHODS: A 12-months
      observational multi-modal intervention study was done, using the top-down and
      bottom-up principle. All hospitalized patients (>3 days) were included. SETTING:
      A university hospital with 758 beds and all specialities. MEASUREMENTS: Record
      audit of GNP, energy- and protein-intake by 24-h recall, patient interviews and
      staff questionnaire before and after the intervention. INTERVENTIONS: Based on
      pre-measurements, nutrition support teams in each department made targeted action
      plans, supervised by an expert team. Education, diagnose-specific nutrition
      plans, improved menus and eating environment, and awareness were initiated.
      STATISTICS: Mann-Whitney and Kruskal-Wallis test was used for ordinal data, and
      Pearson Chi square test for nominative data. RESULTS: Overall 545 patients
      participated (287 before/258 after) from 26/22 departments. There were no
      significant differences regarding sex, age, BMI or previous weight loss before
      and after the intervention. Result-indicators: Energy intake improved from 52% to
      68% (p < 0.007), and protein intake from 33% to 52% (p < 0.001) (>75% of
      requirements). Intake of less than 50% of requirements decreased with 50%.
      Process-indicators: Screening improved from 56% to 77% (p < 0.001), nutrition
      plans from 21% to 56% (p < 0.0001), and monitoring food intake from 29% to 58% (p
      < 0.0001). CONCLUSIONS: Intake of energy and protein as well as GNP improved
      using a multi-modal top-down and bottom-up approach.

PMID- 24874179
TI  - Targeting the extracellular matrix: matricellular proteins regulate cell
      extracellular matrix communication within distinct niches of the intervertebral
      disc.
AB  - The so-called "matricellular" proteins have recently emerged as important
      regulators of cell-extracellular matrix (ECM) interactions. These proteins
      modulate a variety of cell functions through a range of interactions with cell
      surface receptors, hormones, proteases and structural components of the ECM. As
      such, matricellular proteins are crucial regulators of cell phenotype, and
      consequently tissue function. The distinct cell types and microenvironments that
      together form the IVD provide an excellent paradigm to study how matricellular
      proteins mediate communication within and between adjacent tissue types. In
      recent years, the role of several matricellular proteins in the intervertebral
      disc has been explored in vivo using mutant mouse models in which the expression
      of target matricellular proteins was deleted from either one or all compartments
      of the intervertebral disc. The current review outlines what is presently known
      about the roles of the matricellular proteins belonging to the CCN family, SPARC
      (Secreted Protein, Acidic, and Rich in Cysteine), and thrombospondin (TSP) 2 in
      regulating intervertebral disc cell-ECM interactions, ECM synthesis and disc
      tissue homeostasis using genetically modified mouse models. Furthermore, we
      provide a brief overview of recent preliminary studies of other matricellular
      proteins including, periostin (POSTN) and tenascin (TN). Each specific tissue
      type of the IVD contains a different matricellular protein signature, which
      varies based on the specific stage of development, maturity or disease. A growing
      body of direct genetic evidence links IVD development, maintenance and repair to
      the coordinate interaction of matricellular proteins within their respective
      niches and suggests that several of these signaling modulators hold promise in
      the development of diagnostics and/or therapeutics targeting intervertebral disc
      aging and/or degeneration. 

PMID- 24874180
TI  - Synthesis, spectroscopic characterization, and reactivity of water-tolerant Eu3+
      based precatalysts.
AB  - We report the synthesis, spectroscopic characterization, and reactivity of Eu(3+)
      in the presence of a new set of chiral ligands designed for the aqueous,
      enantioselective Mukaiyama aldol reaction. Luminescence and NMR measurements were
      used to characterize the coordination environments of the Eu(3+)-based
      precatalysts, and this data is compared with yields and stereoselectivities. In
      addition to structure-function relationships, we found that, in the presence of
      excess hexadentate ligands, Eu(3+) is coordinatively saturated, and subsequently,
      the reactivity of the precatalysts is reduced. These findings are helpful for the
      design of new ligands that bind Eu(3+) without saturating the Eu(3+) coordination
      sphere. 

PMID- 24874181
TI  - Methods and applications of evolutionary computation in biomedicine.

PMID- 24874183
TI  - Noise model based nu-support vector regression with its application to short-term
      wind speed forecasting.
AB  - Support vector regression (SVR) techniques are aimed at discovering a linear or
      nonlinear structure hidden in sample data. Most existing regression techniques
      take the assumption that the error distribution is Gaussian. However, it was
      observed that the noise in some real-world applications, such as wind power
      forecasting and direction of the arrival estimation problem, does not satisfy
      Gaussian distribution, but a beta distribution, Laplacian distribution, or other
      models. In these cases the current regression techniques are not optimal.
      According to the Bayesian approach, we derive a general loss function and develop
      a technique of the uniform model of nu-support vector regression for the general
      noise model (N-SVR). The Augmented Lagrange Multiplier method is introduced to
      solve N-SVR. Numerical experiments on artificial data sets, UCI data and short
      term wind speed prediction are conducted. The results show the effectiveness of
      the proposed technique. 

PMID- 24874182
TI  - Model-driven approach to data collection and reporting for quality improvement.
AB  - Continuous data collection and analysis have been shown essential to achieving
      improvement in healthcare. However, the data required for local improvement
      initiatives are often not readily available from hospital Electronic Health
      Record (EHR) systems or not routinely collected. Furthermore, improvement teams
      are often restricted in time and funding thus requiring inexpensive and rapid
      tools to support their work. Hence, the informatics challenge in healthcare local
      improvement initiatives consists of providing a mechanism for rapid modelling of
      the local domain by non-informatics experts, including performance metric
      definitions, and grounded in established improvement techniques. We investigate
      the feasibility of a model-driven software approach to address this challenge,
      whereby an improvement model designed by a team is used to automatically generate
      required electronic data collection instruments and reporting tools. To that
      goal, we have designed a generic Improvement Data Model (IDM) to capture the data
      items and quality measures relevant to the project, and constructed Web
      Improvement Support in Healthcare (WISH), a prototype tool that takes user
      generated IDM models and creates a data schema, data collection web interfaces,
      and a set of live reports, based on Statistical Process Control (SPC) for use by
      improvement teams. The software has been successfully used in over 50 improvement
      projects, with more than 700 users. We present in detail the experiences of one
      of those initiatives, Chronic Obstructive Pulmonary Disease project in Northwest
      London hospitals. The specific challenges of improvement in healthcare are
      analysed and the benefits and limitations of the approach are discussed. 

PMID- 24874184
TI  - Relationship between acoustic measures and judgments of intelligibility in
      Parkinson's disease: a within-speaker approach.
AB  - This study investigated the acoustic basis of within-speaker, across-utterance
      variation in sentence intelligibility for 12 speakers with dysarthria secondary
      to Parkinson's disease (PD). Acoustic measures were also obtained for 12 healthy
      controls for comparison to speakers with PD. Speakers read sentences using their
      typical speech style. Acoustic measures of speech rate, articulatory rate,
      fundamental frequency, sound pressure level and F2 interquartile range (F2 IQR)
      were obtained. A group of listeners judged sentence intelligibility using a
      computerized visual-analog scale. Relationships between judgments of
      intelligibility and acoustic measures were determined for individual speakers
      with PD. Relationships among acoustic measures were also quantified. Although
      considerable variability was noted, articulatory rate, fundamental frequency and
      F2 IQR were most frequently associated with within-speaker variation in sentence
      intelligibility. Results suggest that diversity among speakers with PD should be
      considered when interpreting results from group analyses.

PMID- 24874185
TI  - The budding yeast amphiphysin complex is required for contractile actin ring
      (CAR) assembly and post-contraction GEF-independent accumulation of Rho1-GTP.
AB  - The late events of the budding yeast cell division cycle, cytokinesis and cell
      separation, require the assembly of a contractile actomyosin ring (CAR), primary
      and secondary septum formation followed by enzymatic degradation of the primary
      septum. Here we present evidence that demonstrates a role for the budding yeast
      amphiphysin complex, a heterodimer comprising Rvs167 and Rvs161, in CAR assembly
      and cell separation. The iqg1-1 allele is synthetically lethal with both rvs167
      and rvs161 null mutations. We show that both Iqg1 and the amphiphysin complex are
      required for CAR assembly in early anaphase but cells are able to complete
      assembly in late anaphase when these activities are, respectively, either
      compromised or absent. Amphiphysin dependent CAR assembly is dependent upon the
      Rvs167 SH3 domain, but this function is insufficient to explain the observed
      synthetic lethality. Dosage suppression of the iqg1-1 allele demonstrates that
      endocytosis is required for the default cell separation pathway in the absence of
      CAR contraction but is unlikely to be required to maintain viability. The
      amphiphysin complex is required for normal, post-mitotic, localization of Chs3
      and the Rho1 GEF, Rom2, which are responsible for secondary septum deposition and
      the accumulation of GTP bound Rho1 at the bud neck. It is concluded that a
      failure of polarity establishment in the absence of CAR contraction and
      amphiphysin function leads to loss of viability as a result of the consequent
      cell separation defect. 

PMID- 24874186
TI  - Contributions of executive function and spatial skills to preschool mathematics
      achievement.
AB  - Early mathematics achievement is highly predictive of later mathematics
      performance. Here we investigated the influence of executive function (EF) and
      spatial skills, two generalizable skills often overlooked in mathematics
      curricula, on mathematics performance in preschoolers. Children (N=44) of varying
      socioeconomic status (SES) levels were assessed at 3 years of age on a new
      assessment of spatial skill (Test of Spatial Assembly, TOSA) and a vocabulary
      measure (Peabody Picture Vocabulary Test, PPVT). The same children were tested at
      4 years of age on the Beery Test of Visual-Motor Integration (VMI) as well as on
      measures of EF and mathematics. The TOSA was created specifically as an
      assessment for 3-year-olds, allowing the investigation of links among spatial,
      EF, and mathematical skills earlier than previously possible. Results of a
      hierarchical regression indicate that EF and spatial skills predict 70% of the
      variance in mathematics performance without an explicit math test, EF is an
      important predictor of math performance as prior research suggested, and spatial
      skills uniquely predict 27% of the variance in mathematics skills. Additional
      research is needed to understand whether EF is truly malleable and whether EF and
      spatial skills may be leveraged to support early mathematics skills, especially
      for lower SES children who are already falling behind in these skill areas by 3
      and 4 years of age. These findings indicate that both skills are part of an
      important foundation for mathematics performance and may represent pathways for
      improving school readiness for mathematics.

PMID- 24874189
TI  - Palliative self-expandable metal stents for acute malignant colorectal
      obstruction: clinical outcomes and risk factors for complications.
AB  - OBJECTIVE: Self-expandable metal stents (SEMSs) have been used as palliative
      treatment or bridge to surgery for obstructions caused by colorectal cancer
      (CRC). We assessed the long-term outcomes of palliative SEMSs and evaluated the
      risk factors influencing complications. MATERIALS AND METHODS: One hundred and
      seventy-five patients underwent SEMS placement for acute malignant colorectal
      obstruction. Of the 72 patients who underwent palliative treatment for primary
      CRC, 30 patients received chemotherapy (CT) for primary cancer (CT group) and 42
      underwent best supportive treatment (BST) without CT (BST group). RESULTS: There
      was a significant difference in late migration between the CT group and the BST
      group (20.0% in CT group, 2.4% in BST group, p = 0.018). Response to CT
      influenced the rate of late obstruction (0% in disease control, 35.7% in disease
      progression, p = 0.014). However, late obstruction was not associated with stent
      properties, such as diameter or type (<=22 mm vs. >22 mm, 13.5% vs. 14.3%, p =
      1.00; uncovered stent vs. covered stent, 15.5% vs. 7.1%, p = 0.675) and migration
      (<=22 mm vs. >22 mm, 16.2% vs. 2.9%, p = 0.108; uncovered stent vs. covered
      stent, 8.6% vs. 14.3%, p = 0.615) in palliative SEMS. CONCLUSION: The
      administration of CT increases the rate of stent migration, and disease control
      by CT can reduce the risk of obstruction by maintaining the luminal patency of
      palliative SEMSs.

PMID- 24874190
TI  - The effect of gestational age on neonatal outcome in low-risk singleton term
      deliveries.
AB  - OBJECTIVE: To assess the association between gestational age at delivery and
      adverse neonatal outcome among term low-risk singleton neonates. METHODS: A
      retrospective cohort study design was used. The study group included all low-risk
      singleton term (37 + 0 to 41 + 6 weeks) newborns delivered in a single tertiary
      university-affiliated medical center over a 5-year period. Outcome of neonates
      delivered at 37 + 0 to 37 + 6 weeks of gestation (early term) and 41 + 0 to 41 +
      6 weeks of gestation (late term) was compared to that of neonates delivered at 39
      + 0-39 + 6 weeks of gestation (control). RESULTS: Overall, the outcome of 30 229
      neonates was analyzed. The incidence of neonatal mortality was 1.0 per 1000 live
      born neonates, with no significant difference between the various gestational age
      groups. Early term newborns were at higher risk for respiratory morbidity,
      hypoglycemia, hypocalcemia, thrombocytopenia and unexplained jaundice, and had
      higher rates of prolonged hospital stay, NICU admission, sepsis workup and
      antibiotic treatment. On multivariate analysis, early term delivery was an
      independent predictor for composite respiratory morbidity (OR=2.4, 95% CI 1.6
      3.8, p < 0.001), unexplained jaundice (OR=2.1, 95% CI 1.7-2.5, p < 0.001),
      hypoglycemia (OR=2.5, 95% CI 1.5-4.3, p < 0.001) and NICU admission (OR=1.9, 95%
      CI 1.5-2.5, p < 0.001). Late term neonates had a significantly higher rate of
      large for gestational date, but did not differ from controls with respect to the
      rate of composite neurologic or respiratory complications, NICU admission, birth
      trauma or infectious morbidity. CONCLUSION: Even in low-risk singleton
      deliveries, early term is associated with an increased risk of neonatal
      morbidity.

PMID- 24874192
TI  - A simple and accurate liquid chromatography-tandem mass spectrometry method for
      quantification of zonisamide in plasma and its application to a pharmacokinetic
      study.
AB  - Zonisamide (ZNM) is an antiepileptic drug that is used as an adjunctive therapy
      in the treatment of adults with partial seizures. An LC-MS/MS method for
      quantification of ZNM in human and rabbit plasma using (2)H4,(15)N-Zonisamide as
      an internal standard (IS) has been developed and validated. The drug and IS were
      extracted by ether and analyzed on Symmetry((r)) C18 column. Quantitation was
      achieved using ESI-interface employing MRM mode. The method was validated over
      the concentration range of 0.5-50MUg/mL and 0.5-30MUg/mL (r(2)>0.99) in human and
      rabbit plasma samples, respectively. Intra- and inter-run precision of ZNM assay
      in human and rabbit plasma samples ranged from 0.8 to 8.5% with accuracy (bias)
      varied from -11.3 to 14.4% indicating good precision and accuracy. Stability of
      ZNM in human and rabbit plasma samples at various conditions showed that the drug
      was stable under the studied conditions. Analytical recoveries of ZNM and IS from
      spiked human and rabbit plasma samples were in the range of 70.8-77.3% and 85.6
      110.4%, respectively. Matrix effect study showed a lack of matrix effect on mass
      ions of ZNM and IS. The developed method was successfully applied for a
      pharmacokinetic study by measuring ZNM in rabbit plasma samples. Moreover, the
      method is routinely utilized for TDM of ZNM. 

PMID- 24874187
TI  - Protection of retina by alphaB crystallin in sodium iodate induced retinal
      degeneration.
AB  - Age-related macular degeneration (AMD) is a leading cause of blindness in the
      developed world. The retinal pigment epithelium (RPE) is a critical site of
      pathology in AMD and alphaB crystallin expression is increased in RPE and
      associated drusen in AMD. The purpose of this study was to investigate the role
      of alphaB crystallin in sodium iodate (NaIO3)-induced retinal degeneration, a
      model of AMD in which the primary site of pathology is the RPE. Dose dependent
      effects of intravenous NaIO3 (20-70 mg/kg) on development of retinal degeneration
      (fundus photography) and RPE and retinal neuronal loss (histology) were
      determined in wild type and alphaB crystallin knockout mice. Absence of alphaB
      crystallin augmented retinal degeneration in low dose (20 mg/kg) NaIO3-treated
      mice and increased retinal cell apoptosis which was mainly localized to the RPE
      layer. Generation of reactive oxygen species (ROS) was observed with NaIO3 in
      mouse and human RPE which increased further after alphaB crystallin knockout or
      siRNA knockdown, respectively. NaIO3 upregulated AKT phosphorylation and
      peroxisome proliferator-activator receptor-gamma (PPARgamma) which was suppressed
      after alphaB crystallin siRNA knockdown. Further, PPARgamma ligand inhibited
      NaIO3-induced ROS generation. Our data suggest that alphaB crystallin plays a
      critical role in protection of NaIO3-induced oxidative stress and retinal
      degeneration in part through upregulation of AKT phosphorylation and PPARgamma
      expression. 

PMID- 24874188
TI  - Technology advancement for integrative stem cell analyses.
AB  - Scientists have endeavored to use stem cells for a variety of applications
      ranging from basic science research to translational medicine. Population-based
      characterization of such stem cells, while providing an important foundation to
      further development, often disregard the heterogeneity inherent among individual
      constituents within a given population. The population-based analysis and
      characterization of stem cells and the problems associated with such a blanket
      approach only underscore the need for the development of new analytical
      technology. In this article, we review current stem cell analytical technologies,
      along with the advantages and disadvantages of each, followed by applications of
      these technologies in the field of stem cells. Furthermore, while recent advances
      in micro/nano technology have led to a growth in the stem cell analytical field,
      underlying architectural concepts allow only for a vertical analytical approach,
      in which different desirable parameters are obtained from multiple individual
      experiments and there are many technical challenges that limit vertically
      integrated analytical tools. Therefore, we propose--by introducing a concept of
      vertical and horizontal approach--that there is the need of adequate methods to
      the integration of information, such that multiple descriptive parameters from a
      stem cell can be obtained from a single experiment.

PMID- 24874193
TI  - Validation of a structural comparison of the antigenic characteristics of Usutu
      virus and West Nile virus envelope proteins.
AB  - Cross-reactions observed in serological assays between Usutu virus (USUV), the
      USUV outlier subtype strain CAR_1969 and West Nile virus (WNV) suggest that they
      share antigenic features amongst their structural outer proteins especially
      envelope (E) proteins. To investigate the molecular background of this
      observation, we compared the E protein sequences of seven USUV strains, USUV
      subtype strain CAR_1969 and WNV strain 2471, focusing on the binding site defined
      by the WNV neutralizing antibody E16. USUV SouthAfrica_1959 differs from WNV 2741
      in three of four residues critical for E16 antibody binding and five of the 12
      additionally involved residues. In contrast, USUV subtype CAR_1969 differs from
      WNV 2741 in two critical residues and five additional residues. Furthermore, USUV
      subtype CAR_1969 differs from other USUV strains in two critical residues. E16
      antibody binding has previously been shown to be highly specific for WNV; thus,
      the observed variation in amino acid residues suggests that the region
      corresponding to the WNV E16 epitope is probably not responsible for the observed
      cross-reactions between WNV and USUV. Seroneutralisation assays confirmed these
      findings for WNV and USUV, however, showed occurring cross-reactivity between WNV
      and USUV subtype CAR_1969 at high antibody titers. The sequence diversity in this
      region might also explain some of the observed different antigenic
      characteristics of USUV strains and USUV subtype CAR_1969. A therapeutic effect
      of E16 antibody has been described in WNV infected mice; therefore, a USUV
      specific antibody generated against the region corresponding to the WNV E16
      binding site might represent an approach for treating USUV infections. 

PMID- 24874194
TI  - A new ophiovirus is associated with blueberry mosaic disease.
AB  - Blueberry mosaic disease (BMD) was first described more than 60 years ago and is
      caused by a yet unidentified graft transmissible agent. A combination of
      traditional methods and next generation sequencing disclosed the presence of a
      new ophiovirus in symptomatic plants. The virus was detected in all BMD samples
      collected from several production areas of North America and was thus named
      blueberry mosaic associated virus. Phylogenetic analysis, supported by high
      bootstrap values, places the virus within the family Ophioviridae. The genome
      organization resembles that of citrus psorosis virus, the type member of the
      genus Ophiovirus. The implications of this discovery in BMD control and blueberry
      virus certification schemes are also discussed. 

PMID- 24874195
TI  - Genetic diversification of penaeid shrimp infectious myonecrosis virus between
      Indonesia and Brazil.
AB  - Infectious myonecrosis virus (IMNV) is a pathogen of penaeid shrimp, most notably
      the whiteleg shrimp Litopenaeus vannamei. First discovered in L. vannamei from
      Brazilian aquaculture farms in 2003, IMNV was additionally confirmed in L.
      vannamei from Indonesian farms in 2006 and has since been found in numerous
      provinces there. Only two complete sequences of IMNV strains have been reported
      to date, one strain from the Brazilian state of Piaui collected in 2003 and
      another from the Indonesian province of East Java collected in 2006. In this
      study, we determined the complete sequences of two additional Indonesian strains,
      one from Lampung province collected in 2011 and another from East Java province
      collected in 2012. We also determined partial sequences for six other strains to
      enhance phylogenetic comparisons, which have heretofore been limited by the small
      number of reported sequences, including only one for an Indonesian strain. The
      new results demonstrate clear genetic diversification of IMNV between Indonesia
      and Brazil, as well as within Indonesia. Analyses of conserved sequence motifs
      suggest a revised RNA pseudoknot prediction for ribosomal frameshifting. 

PMID- 24874196
TI  - Biodiversity and evolution of Imjin virus and Thottapalayam virus in Crocidurinae
      shrews in Zhejiang Province, China.
AB  - The recent discovery of numerous hantaviruses in insectivores has provided a new
      view of hantavirus biodiversity and evolution. To determine the presence and
      genetic diversity of Imjin virus (MJNV) and Thottapalayam virus (TPMV) in
      insectivores in Zhejiang Province, China, we captured and performed virus
      screening of 32 Ussuri white-toothed shrews (Crocidura lasiura) and 105 Asian
      house shrews (Suncus murinus) in different coastal regions. Hantavirus genome (S,
      M, and L segments) sequences were successfully recovered from one Ussuri white
      toothed shrew and seven Asian house shrews. Phylogenetic analysis revealed that
      the virus carried by the Ussuri white-toothed shrew was most closely related to
      MJNV, but with >15% nucleotide sequence difference, suggesting that it represents
      a new subtype. The hantaviruses carried by Asian house shrews were closely
      related to the TPMV variants found in the same geographic area, but more
      distantly related to those sampled in India and Nepal. Additionally, the TPMV
      sequences obtained in this study, as well as those found previously in this area,
      could be divided into three lineages reflecting their geographic origins,
      indicative of largely allopatric evolution. Overall, our data highlights the high
      genetic diversity of insectivore-borne hantaviruses in China, suggesting that
      more may be discovered in the future. 

PMID- 24874197
TI  - Recombinant pestivirus E2 glycoproteins prevent viral attachment to permissive
      and non permissive cells with different efficiency.
AB  - Bovine viral diarrhoea virus (BVDV) is an economically important animal pathogen,
      which like other pestiviruses has similar molecular biological features to
      hepaciviruses, including human Hepatitis C virus. The pestivirus E2 glycoproteins
      are the major target for virus-neutralising antibodies, as well as playing a role
      in receptor binding and host range restriction. In this study, recombinant E2
      glycoproteins (rE2) derived from three different pestivirus species were examined
      for their inhibitory effects on pestivirus infectivity in cell culture. Histidine
      tagged rE2 glycoproteins of BVDV type 2 strain 178003, BVDV type 1 strain Oregon
      C24V and CSFV strain Alfort 187 were produced in Spodoptera frugiperda insect
      cells and purified under native conditions. The ability of rE2 glycoprotein to
      inhibit the infection of permissive cells by both homologous and heterologous
      virus was compared, revealing that the inhibitory effects of rE2 glycoproteins
      correlated with the predicted similarity of the E2 structures in the recombinant
      protein and the test virus. This result suggests that the sequence and structure
      of E2 are likely to be involved in the host specificity of pestiviruses at their
      point of uptake into cells. 

PMID- 24874199
TI  - The interaction between host Annexin A2 and viral Nsp9 is beneficial for
      replication of porcine reproductive and respiratory syndrome virus.
AB  - Non-structural protein 9 (Nsp9), a RNA-dependent RNA polymerase (RdRp) of the
      porcine reproductive and respiratory syndrome virus (PRRSV), is necessary for
      PRRSV replication. However, the binding partners of Nsp9 have not been
      identified. In this study, seven host proteins were identified as Nsp9-binding
      proteins using yeast two-hybrid (Y2H). Among of them, we confirmed the
      interaction of Nsp9 with Annexin A2 (ANXA2) using Y2H, Co-immunoprecipitation (Co
      IP), GST pulldown and immunofluorescence assay (IFA). We found that only full
      length ANXA2 could bind with Nsp9 in vitro and Nsp9 interacted with endogenous
      ANXA2 in PRRSV-infected MARC-145 cells. In addition, we found that the Nsp9-ANXA2
      interaction was partially reduced by RNase A treatment. Furthermore, PRRSV growth
      was significantly hindered in ANXA2-knockdown MARC-145 cells. Taken together,
      these results indicate that Nsp9 binding partner ANXA2 is beneficial for PRRSV
      replication. 

PMID- 24874198
TI  - The hepatitis C virus core protein can modulate RNA-dependent RNA synthesis by
      the 2a polymerase.
AB  - RNA replication enzymes are multi-subunit protein complexes whose activity can be
      modulated by other viral and cellular factors. For genotype 1b Hepatitis C virus
      (HCV), the RNA-dependent RNA polymerase (RdRp) subunit of the replicase, NS5B,
      has been reported to interact with the HCV Core protein to decrease RNA synthesis
      (Kang et al., 2009). Here we used a cell-based assay for RNA synthesis to examine
      the Core-NS5B interaction of genotype 2a HCV. Unlike the 1b NS5B, the activity of
      the 2a NS5B was stimulated by the Core protein. Using the bimolecular
      fluorescence complementation assay, the 2a Core co-localized with 2a NS5B when
      they were transiently expressed in cells. The two proteins can form a co
      immunoprecipitable complex. Deletion analysis showed that the N-terminal 75
      residues of 2a Core were required to contact 2a NS5B to modulate its activity.
      The C-terminal transmembrane helix of 2a NS5B also contributes to the interaction
      with the 2a Core. To determine the basis for the differential effects of the Core
      RdRp interaction, we found that the 2a RdRp activity was enhanced by both the 1b
      Core and 2a Core. However, the 1b NS5B activity was slightly inhibited by either
      Core protein. The replication of the 2a JFH-1 replicon was increased by co
      expressed 2a Core while the genotype 1b Con1 replicon was not significantly
      affected by the corresponding Core. Mutations in 2a NS5B that affected the closed
      RdRp structure were found to be less responsive to 2a Core. Finally, we
      determined that RNA synthesis by the RdRps from genotypes 2a, 3a and 4a HCV were
      increased by the Core proteins from HCV of genotypes 1-4. These results reveal
      another difference between RNA syntheses by the different genotype RdRps and add
      additional examples of a viral structural protein regulating viral RNA synthesis.

PMID- 24874200
TI  - Influence of previous heart failure hospitalization on cardiovascular events in
      patients with reduced and preserved ejection fraction.
AB  - BACKGROUND: Hospitalization for acute heart failure (HF) is associated with high
      rates of subsequent mortality and readmission. We assessed the influence of the
      time interval between previous HF hospitalization and randomization in the
      Candesartan in Heart failure: Reduction in Mortality and morbidity (CHARM) trials
      on clinical outcomes in patients with both reduced and preserved ejection
      fraction. METHODS AND RESULTS: CHARM enrolled 7599 patients with New York Heart
      Association class II to IV HF, of whom 5426 had a history of previous HF
      hospitalization. Cox proportional hazards regression models were used to assess
      the association between time from previous HF hospitalization and randomization
      and the primary outcome of cardiovascular death or unplanned admission to
      hospital for the management of worsening HF during a median of 36.6 months. For
      patients with HF and reduced or preserved ejection fraction, rates of
      cardiovascular mortality and HF hospitalization were higher among patients with
      previous HF hospitalization than those without. The risk for mortality and
      hospitalization varied inversely with the time interval between hospitalization
      and randomization. Rates were higher for patients with HF and reduced ejection
      fraction within each category. Event rates for those with HF with preserved
      ejection fraction and a HF hospitalization in the 6 months before randomization
      were comparable with the rate in patients with HF and reduced ejection fraction
      with no previous HF hospitalization. CONCLUSIONS: Rates of cardiovascular death
      or HF hospitalization are greatest in those who have been previously hospitalized
      for HF. Independent of EF, rates of death and readmission decline as time from HF
      hospitalization to trial enrollment increased. Recent HF hospitalization
      identifies a high-risk population for future clinical trials in HF and reduced
      ejection fraction and HF with preserved ejection fraction. CLINICAL TRIAL
      REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00634400.

PMID- 24874201
TI  - Ranolazine effectively suppresses atrial fibrillation in the setting of heart
      failure.
AB  - BACKGROUND: There is a critical need for safer and more effective pharmacological
      management of atrial fibrillation (AF) in the setting of heart failure (HF).
      METHODS AND RESULTS: This study investigates the electrophysiological,
      antiarrhythmic, and proarrhythmic effects of a clinically relevant concentration
      of ranolazine (5 MUmol/L) in coronary-perfused right atrial and left ventricular
      preparations isolated from the hearts of HF dogs. HF was induced by ventricular
      tachypacing (2-6 weeks at 200-240 beats per minute; n=17). Transmembrane action
      potentials were recorded using standard microelectrode techniques. In atria,
      ranolazine slightly prolonged action potential duration but significantly
      depressed sodium channel current-dependent parameters causing a reduction of
      maximum rate of rise of the action potential upstroke, a prolongation of the
      effective refractory period secondary to the development of postrepolarization
      refractoriness, and an increase in diastolic threshold of excitation and atrial
      conduction time. Ranolazine did not significantly alter these parameters or
      promote arrhythmias in the ventricles. Ranolazine produced greater inhibition of
      peak sodium channel current in atrial cells isolated from HF versus normal dogs.
      A single premature beat reproducibly induced self-terminating AF in 10 of 17
      atria. Ranolazine (5 MUmol/L) suppressed induction of AF in 7 of 10 (70%) atria.
      In the remaining 3 atria, ranolazine reduced frequency and duration of AF.
      CONCLUSIONS: Our results demonstrate more potent suppression of AF by ranolazine
      in the setting of HF than previously demonstrated in nonfailing hearts and
      absence of ventricular proarrhythmia. The data suggest that ranolazine may be of
      benefit as an alternative to amiodarone and dofetilide in the management of AF in
      patients with HF.

PMID- 24874204
TI  - Maximizing omnidirectional light harvesting in metal oxide hyperbranched array
      architectures.
AB  - The scrupulous design of nanoarchitectures and smart hybridization of specific
      active materials are closely related to the overall photovoltaic performance of
      an anode electrode. Here we present a solution-based strategy for the fabrication
      of well-aligned metal oxide-based nanowire-nanosheet-nanorod hyperbranched arrays
      on transparent conducting oxide substrates. For these hyperbranched arrays, we
      observe a twofold increment in dye adsorption and enhanced light trapping and
      scattering capability compared with the pristine titanium dioxide nanowires, and
      thus a power conversion efficiency of 9.09% is achieved. Our growth approach
      presents a strategy to broaden the photoresponse and maximize the light
      harvesting efficiency of arrays architectures, and may lead to applications for
      energy conversion and storage, catalysis, water splitting and gas sensing. 

PMID- 24874202
TI  - Integrating artificial with natural cells to translate chemical messages that
      direct E. coli behaviour.
AB  - Previous efforts to control cellular behaviour have largely relied upon various
      forms of genetic engineering. Once the genetic content of a living cell is
      modified, the behaviour of that cell typically changes as well. However, other
      methods of cellular control are possible. All cells sense and respond to their
      environment. Therefore, artificial, non-living cellular mimics could be
      engineered to activate or repress already existing natural sensory pathways of
      living cells through chemical communication. Here we describe the construction of
      such a system. The artificial cells expand the senses of Escherichia coli by
      translating a chemical message that E. coli cannot sense on its own to a molecule
      that activates a natural cellular response. This methodology could open new
      opportunities in engineering cellular behaviour without exploiting genetically
      modified organisms. 

PMID- 24874205
TI  - Hybrid surface-phonon-plasmon polariton modes in graphene/monolayer h-BN
      heterostructures.
AB  - Infrared transmission measurements reveal the hybridization of graphene plasmons
      and the phonons in a monolayer hexagonal boron nitride (h-BN) sheet. Frequency
      wavevector dispersion relations of the electromagnetically coupled graphene
      plasmon/h-BN phonon modes are derived from measurement of nanoresonators with
      widths varying from 30 to 300 nm. It is shown that the graphene plasmon mode is
      split into two distinct optical modes that display an anticrossing behavior near
      the energy of the h-BN optical phonon at 1370 cm(-1). We explain this behavior as
      a classical electromagnetic strong-coupling with the highly confined near fields
      of the graphene plasmons allowing for hybridization with the phonons of the
      atomically thin h-BN layer to create two clearly separated new surface-phonon
      plasmon-polariton (SPPP) modes.

PMID- 24874203
TI  - Longitudinal trajectories and associated baseline predictors in youths with
      bipolar spectrum disorders.
AB  - OBJECTIVE: The authors sought to identify and evaluate longitudinal mood
      trajectories and associated baseline predictors in youths with bipolar disorder.
      METHOD: A total of 367 outpatient youths (mean age, 12.6 years) with bipolar
      disorder with at least 4 years of follow-up were included. After intake,
      participants were interviewed on average 10 times (SD=3.2) over a mean of 93
      months (SD=8.3). Youths and parents were interviewed for psychopathology,
      functioning, treatment, and familial psychopathology and functioning. RESULTS:
      Latent class growth analysis showed four different longitudinal mood
      trajectories: "predominantly euthymic" (24.0%), "moderately euthymic" (34.6%),
      "ill with improving course" (19.1%), and "predominantly ill" (22.3%). Within each
      class, youths were euthymic on average 84.4%, 47.3%, 42.8%, and 11.5% of the
      follow-up time, respectively. Multivariate analyses showed that better course was
      associated with higher age at onset of mood symptoms, less lifetime family
      history of bipolar disorder and substance abuse, and less history at baseline of
      severe depression, manic symptoms, suicidality, subsyndromal mood episodes, and
      sexual abuse. Most of these factors were more noticeable in the "predominantly
      euthymic" class. The effects of age at onset were attenuated in youths with lower
      socioeconomic status, and the effects of depression severity were absent in those
      with the highest socioeconomic status. CONCLUSIONS: A substantial proportion of
      youths with bipolar disorder, especially those with adolescent onset and the
      above-noted factors, appear to be euthymic over extended periods. Nonetheless,
      continued syndromal and subsyndromal mood symptoms in all four classes underscore
      the need to optimize treatment.

PMID- 24874207
TI  - How a fish can fry: scientists uncover evolutionary clues behind electric fish.

PMID- 24874206
TI  - Bacteriophage-fused peptides for serodiagnosis of human strongyloidiasis.
AB  - BACKGROUND: Strongyloidiasis, a human intestinal infection caused by the nematode
      Strongyloides stercoralis, is frequently underdiagnosed and although its high
      prevalence is still a neglected parasitic disease because conventional diagnostic
      tests based on parasitological examination (presence of Strongyloides larvae in
      stool) are not sufficiently sensitive due to the low parasitic load and to the
      irregular larval output. There is an urgent need to improve diagnostic assays,
      especially for immunocompromised patients with high parasitic load as consequence
      of self-infection cycle, which can disseminate throughout the body, resulting in
      a potentially fatal hyperinfection syndrome often accompanied by sepsis or
      meningitis. METHODS/PRINCIPAL FINDINGS: We have performed Phage Display
      technology to select peptides that mimic S. stercoralis antigens, capable of
      detecting a humoral response in patients with strongyloidiasis. The peptides
      reactivity was investigated by Phage-ELISA through different panels of serum
      samples. We have successfully selected five peptides with significant
      immunoreactivity to circulating IgG from patients' sera with strongyloidiasis.
      The phage displayed peptides C9 and C10 presented the highest diagnostic
      potential (AUC>0.87) with excellent sensitivity (>85%) and good specificity
      (>77.5%), suggesting that some S. stercoralis antigens trigger systemic immune
      response. CONCLUSIONS/SIGNIFICANCE: These novel antigens are interesting serum
      biomarkers for routine strongyloidiasis screenings due to the easy production and
      simple assay using Phage-ELISA. Such markers may also present a promising
      application for therapeutic monitoring.

PMID- 24874208
TI  - Timing and order of transmission events is not directly reflected in a pathogen
      phylogeny.
AB  - Pathogen phylogenies are often used to infer spread among hosts. There is,
      however, not an exact match between the pathogen phylogeny and the host
      transmission history. Here, we examine in detail the limitations of this
      relationship. First, all splits in a pathogen phylogeny of more than 1 host occur
      within hosts, not at the moment of transmission, predating the transmission
      events as described by the pretransmission interval. Second, the order in which
      nodes in a phylogeny occur may be reflective of the within-host dynamics rather
      than epidemiologic relationships. To investigate these phenomena, motivated by
      within-host diversity patterns, we developed a two-phase coalescent model that
      includes a transmission bottleneck followed by linear outgrowth to a maximum
      population size followed by either stabilization or decline of the population.
      The model predicts that the pretransmission interval shrinks compared with
      predictions based on constant population size or a simple transmission
      bottleneck. Because lineages coalesce faster in a small population, the
      probability of a pathogen phylogeny to resemble the transmission history depends
      on when after infection a donor transmits to a new host. We also show that the
      probability of inferring the incorrect order of multiple transmissions from the
      same host is high. Finally, we compare time of HIV-1 infection informed by
      genetic distances in phylogenies to independent biomarker data, and show that,
      indeed, the pretransmission interval biases phylogeny-based estimates of when
      transmissions occurred. We describe situations where caution is needed not to
      misinterpret which parts of a phylogeny that may indicate outbreaks and tight
      transmission clusters. 

PMID- 24874209
TI  - Methane uptake in forest soils along an urban-to-rural gradient in Pearl River
      Delta, South China.
AB  - We investigated soil CH4 fluxes from six forests along an urban-to-rural gradient
      in Guangzhou City metropolitan area, South China. The most significant CH4
      consumption was found in the rural site, followed by suburban, and then urban
      forest sites. The rates of CH4 uptake were significantly higher (by 38% and 44%,
      respectively for mixed forest and broadleaf forest) in the rural than in the
      urban forest site. The results indicate that soil water filled pore space (WFPS)
      is the primary factor for controlling CH4 consumption in subtropical forests. The
      reductions of soil CH4 uptake in urban forests were also influenced by the higher
      rates of atmospheric nitrogen (N) deposition and increases in soil nitrate (NO3(
      )) and aluminum (Al(3+)) contents as a result of urbanization. Results from this
      work suggest that environmental changes associated with urbanization could
      decrease soil CH4 consumption in subtropical forests and potentially contribute
      to increase of atmospheric CH4 concentration. 

PMID- 24874210
TI  - Update on surgery for velopharyngeal dysfunction.
AB  - PURPOSE OF REVIEW: To review journal articles discussing surgery for
      velopharyngeal dysfunction over the past year. All articles ascertained by a
      PubMed search relevant to this topic were reviewed. RECENT FINDINGS: Articles
      evaluated from the past year discussed the variations, effectiveness, and
      feasibility of multiple surgical techniques for velopharyngeal dysfunction,
      including the Furlow palatoplasty, sphincter pharyngoplasty, pharyngeal flap
      procedure, and other less known novel surgical options. Outcomes, comparisons,
      and complications were a focus of the majority of the studies. Combinations of
      the above procedures are also assessed. Nonsurgical options, such as prosthetic
      devices and pharyngeal augmentation, are mentioned. SUMMARY: Multiple surgical
      options exist to assist patients with velopharyngeal dysfunction. The majority of
      the surgical options can be highly successful. A multispecialty team is critical
      in providing patients with the most appropriate treatment for their specific
      situation. Standardized speech and velopharyngeal dysfunction outcome measures
      are necessary to allow accurate preoperative and postoperative comparisons,
      intrasurgeon comparisons, and multi-institutional comparisons. Unfortunately,
      there is a lack of standardization in speech outcome measures among the studies
      published over the last year. The risk of postoperative obstructive sleep apnea
      must be assessed and discussed prior to surgery for any patient scheduled to
      undergo surgery for velopharyngeal dysfunction. Future studies promise to improve
      our understanding of velopharyngeal dysfunction and provide further guidance as
      to the best surgical options to assist these patients.

PMID- 24874211
TI  - Tissue-engineered cartilage for facial plastic surgery.
AB  - PURPOSE OF REVIEW: The reconstruction of cartilaginous craniofacial defects is
      ideally performed with analogous grafting material, such as autologous tissue.
      However, the use of autologous cartilage is limited by its finite availability
      and potentially suboptimal geometry to repair specific defects. Tissue
      engineering of human cartilage may provide the adequate supply of grafting and
      implant material for the reconstruction of cartilaginous facial defects. An
      update of the various cartilage tissue engineering methodologies is provided in
      this review. RECENT FINDINGS: The cartilage tissue engineering paradigm begins
      with the harvest of a small septal cartilage donor specimen. This is followed by
      the isolation and subsequent proliferation of chondrocytes and the seeding of
      these cells onto three-dimensional scaffolds. Neocartilage is created as
      pericellular substrate, is produced by the cells and deposited throughout the
      scaffold. Theoretically, the mature cartilage construct can be introduced back
      into the same patient for reconstruction of craniofacial defects. Initial steps
      of the cartilage tissue engineering protocol have been standardized; however,
      modifications of subsequent steps have shown the potential to profoundly impact
      tissue composition and strength, bringing the properties of cartilage constructs
      closer to those of native human septum. SUMMARY: The ability to engineer
      virtually limitless quantities of autologous cartilage could have a profound
      impact on facial plastic and reconstructive surgery. The strategies used to
      refine human cartilage culture techniques have successfully produced neocartilage
      constructs with biochemical and biomechanical properties approaching those of
      native septal tissue. With the steady progress achieved in recent years, there is
      great capacity for the proximate realization of surgically implantable tissue
      engineered cartilage constructs.

PMID- 24874212
TI  - Update on outcomes research for cleft lip and palate.
AB  - PURPOSE OF REVIEW: The purpose of this review is to summarize the recent evidence
      based literature focusing on cleft lip and palate outcomes research. RECENT
      FINDINGS: The findings of recently published literature focus on cleft lip and
      palate outcomes research, patient-based outcomes measurement tools, nasoalveolar
      molding, and how speech outcomes relate to palatoplasty timing, technique, and
      intravelar veloplasty. Studies have investigated the relationship between
      palatoplasty timing and facial development. SUMMARY: The literature lacks any
      evidence-based consensus to support a superior method of cleft lip repair. A
      majority of North American surgeons, however, utilize a rotation-advancement
      technique and perform cleft rhinoplasty at the time of primary lip repair, with
      the idea that this could decrease the number of revision surgeries needed over
      the long term. Most cleft surgeons perform a single-stage palatoplasty at 9-12
      months of age for improved early speech outcomes. There is insufficient evidence
      to support a two-stage palatoplasty with the intention of improved maxillary
      growth. Controversy persists on the relationship between early palatal surgery
      and its deleterious effects on facial development. A shift toward patient
      reported outcomes is called for; however, this remains difficult, as there are
      few validated, cleft-specific outcome measurement tools.

PMID- 24874213
TI  - Boron-nitride and aluminum-nitride "Pringles" and flapping motion.
AB  - Motivated by the recent successful synthesis of a new nanocarbon, namely, a
      warped, double-concave graphene "Pringle" (Nat. Chem., 2013, 5, 739), we
      investigate properties of warped boron-nitride (BN) and aluminum-nitride (AlN)
      analogues, i.e., the non-planar B40N40H30 and Al40N40H30 "Pringles" using density
      functional theory (DFT) calculations. Particular attention is placed on the
      effect of non-hexagonal rings on the stability and physical properties of BN and
      AlN Pringles. We find that the warped BN and AlN Pringles with one pentagon and
      five heptagons are stable without imaginary frequencies. Both the warped
      B40N40H30 and Al40N40H30 Pringles are expected to be flexible in solution as both
      can periodically change their shape in a dynamic "flapping" fashion due to their
      much lower activation barrier of racemization compared to that of the C80H30
      counterpart. Since the warped B40N40H30 possesses a smaller HOMO-LUMO gap than
      the planar B39N39H30, it is expected that incorporating non-hexagonal ring
      defects by design can be an effective way to modify electronic properties of BN
      based nanoplates. 

PMID- 24874214
TI  - Aluminum interaction with glutamate and alpha-ketoglutarate: a computational
      study.
AB  - Aluminum, although a nonessential element in the human body, has been found to be
      involved in a variety of diseases. Thus, it has recently been reported that
      aluminum interferes with the metabolic tricarboxylic acid cycle, in which alpha
      ketoglutarate (alpha-KG) is involved. alpha-KG is transformed to glutamate (or
      vice versa) by glutamate dehydrogenase (GDH). Al(III) inhibits the normal
      function of GDH, and it was speculated that the reason for this inhibition is
      triggered by the Al(III)-assisted tautomerization of alpha-KG from keto to enol.
      In the present study, we investigate the interaction of both tautomers of alpha
      KG with Al(III) as well the complexation of glutamate to the metal. The results
      confirm that Al(III) indeed displaces the tautomerization reaction and favors the
      enol form of alpha-KG by 28 kcal/mol. However, when citrate is included in the
      system, the stabilization of the enol tautomer decreases, as this tautomer is
      only 1.5 kcal/mol more stable than the keto form of alpha-KG. Finally, possible
      routes for the complexation of these molecules to Al(III) in a biological
      environment are discussed; we propose that the ternary complexes formed by
      Al(III), citrate, and alpha-KG or glutamate can be the more likely species. 

PMID- 24874217
TI  - [Safe surgery and clinical recommendation].

PMID- 24874216
TI  - Fundamental limits of scintillation detector timing precision.
AB  - In this paper we review the primary factors that affect the timing precision of a
      scintillation detector. Monte Carlo calculations were performed to explore the
      dependence of the timing precision on the number of photoelectrons, the
      scintillator decay and rise times, the depth of interaction uncertainty, the time
      dispersion of the optical photons (modeled as an exponential decay), the
      photodetector rise time and transit time jitter, the leading-edge trigger level,
      and electronic noise. The Monte Carlo code was used to estimate the practical
      limits on the timing precision for an energy deposition of 511 keV in 3 mm * 3 mm
      * 30 mm Lu2SiO5:Ce and LaBr3:Ce crystals. The calculated timing precisions are
      consistent with the best experimental literature values. We then calculated the
      timing precision for 820 cases that sampled scintillator rise times from 0 to 1.0
      ns, photon dispersion times from 0 to 0.2 ns, photodetector time jitters from 0
      to 0.5 ns fwhm, and A from 10 to 10,000 photoelectrons per ns decay time. Since
      the timing precision R was found to depend on A(-1/2) more than any other factor,
      we tabulated the parameter B, where R = BA(-1/2). An empirical analytical formula
      was found that fit the tabulated values of B with an rms deviation of 2.2% of the
      value of B. The theoretical lower bound of the timing precision was calculated
      for the example of 0.5 ns rise time, 0.1 ns photon dispersion, and 0.2 ns fwhm
      photodetector time jitter. The lower bound was at most 15% lower than leading
      edge timing discrimination for A from 10 to 10,000 photoelectrons ns(-1). A
      timing precision of 8 ps fwhm should be possible for an energy deposition of 511
      keV using currently available photodetectors if a theoretically possible
      scintillator were developed that could produce 10,000 photoelectrons ns(-1).

PMID- 24874218
TI  - [20 years emergency surgery of abdominal organs in Moscow].
AB  - The analysis of emergency surgical care in medical institution of Moscow for the
      last 20 years is presented in the article. There were 912 156 patients with acute
      appendicitis, strangulated hernia, perforated gastro-duodenal ulcer, gastro
      duodenal bleeding, acute cholecystitis, acute pancreatitis, acute intestinal
      obstruction on treatment during this period. It was observed reduction overall
      and postoperative mortality. It was concluded that positive results are caused by
      development of material and technical base, transition on clock mode of
      diagnostic units, increase of patients? number hospitalized in department of
      intensive care for operation training and after it, using of modern diagnostic
      and therapeutic methods, edit documents regulating of health facilities activity
      according to medicine development. 

PMID- 24874215
TI  - Targeting membrane-bound viral RNA synthesis reveals potent inhibition of diverse
      coronaviruses including the middle East respiratory syndrome virus.
AB  - Coronaviruses raise serious concerns as emerging zoonotic viruses without
      specific antiviral drugs available. Here we screened a collection of 16671
      diverse compounds for anti-human coronavirus 229E activity and identified an
      inhibitor, designated K22, that specifically targets membrane-bound coronaviral
      RNA synthesis. K22 exerts most potent antiviral activity after virus entry during
      an early step of the viral life cycle. Specifically, the formation of double
      membrane vesicles (DMVs), a hallmark of coronavirus replication, was greatly
      impaired upon K22 treatment accompanied by near-complete inhibition of viral RNA
      synthesis. K22-resistant viruses contained substitutions in non-structural
      protein 6 (nsp6), a membrane-spanning integral component of the viral replication
      complex implicated in DMV formation, corroborating that K22 targets membrane
      bound viral RNA synthesis. Besides K22 resistance, the nsp6 mutants induced a
      reduced number of DMVs, displayed decreased specific infectivity, while RNA
      synthesis was not affected. Importantly, K22 inhibits a broad range of
      coronaviruses, including Middle East respiratory syndrome coronavirus (MERS-CoV),
      and efficient inhibition was achieved in primary human epithelia cultures
      representing the entry port of human coronavirus infection. Collectively, this
      study proposes an evolutionary conserved step in the life cycle of positive
      stranded RNA viruses, the recruitment of cellular membranes for viral
      replication, as vulnerable and, most importantly, druggable target for antiviral
      intervention. We expect this mode of action to serve as a paradigm for the
      development of potent antiviral drugs to combat many animal and human virus
      infections. 

PMID- 24874220
TI  - [Bronchopulmonary ACTH-producing tumors].
AB  - Neuroendocrine tumors have the ability to produce the hormones and vasoactive
      peptides. Excess of these hormones leads to different symptoms and syndromes
      because of organs' injuries. Detection of ACTH origin by using of modern
      diagnostic methods is not always possible. Lungs and bronchi are one of the most
      frequent localization of ACTH-producing tumors. It is considered that carcinoids
      with bronchopulmonary localization like a benign tumors in the clinical course.
      But at the same time carcinoid tends to metastasize, so timely diagnostics and
      treatment improve quality of life significant and increase the life expectancy of
      patients. The modern state of diagnostics and surgical treatment problem of ACTH
      producing tumors with bronchopulmonary localization is presented in the article.
      It was described the brief historical background, clinical symptoms, instrumental
      and biochemical methods of diagnosis. The principles of surgical treatment are
      presented in the article. 

PMID- 24874219
TI  - [Risk factors and causes of hospital mortality after Bentall-deBono's surgery].
AB  - It was done an evaluation of surgical treatment results of 71 patients with
      aortic arch aneurysm and aortic insufficiency, who were operated routinely.
      According to data of correlation and multiple regression analysis, chronic
      obstructive pulmonary disease and kidney disease before operation are significant
      factors predisposing to death in postoperative period. The authors consider that
      normalization of lungs and kidneys function before operation improves surgical
      treatment results in patients of this group. 

PMID- 24874221
TI  - [Gastrectomy with spleen preservation in patients with stomach cancer].
AB  - It was analyzed the results of surgical treatment of 118 patients with stomach
      cancer. Lymphadenectomy and gastrectomy were done in all cases. All patients were
      divided into two groups. Gastrectomy and splenectomy were performed in the first
      group, gastrectomy with preservation of spleen was done in the second group. It
      was revealed that splenectomy is not an independent prognostic factor influencing
      on prolonged survival of patients with stomach cancer. Preservation of spleen
      permits to reduce the number of early postoperative complications. 

PMID- 24874222
TI  - [Long-term results of surgical treatment of patients with cancer of
      biliopancreaticoduodenal area].
AB  - 500 patients with cancer of biliopancreaticoduodenal area who underwent treatment
      and survey in the hospital at the period from 1986 to December 2011 years were
      included in the study. There were 212 (42.4%) males and 288 (57.6%) females. It
      was analyzed the long-term results of palliative surgical interventions in 72
      (40.2%) patients and endoscopic interventions in 107 (65.2%) patients. It was
      done a comparative analysis of palliative interventions results. It was concluded
      that both methods have high efficiency for resolution of obstructive jaundice.
      Average survival rate of patients depends on the biliary decompression method (8
      months after surgical interventions and 7 months after endoscopic interventions).
      It was analyzed the long-term results of radical surgery in 55 (78.5%) patients.
      It was concluded that the best 5-years survival rate was in patients with major
      papilla cancer without invasion into mesenterical vessels (54.2%). 5-years
      survival rate was observed only in 2 patients in case of pancreatic head and
      terminal bile duct cancer. And lifetime of the majority did not exceed 3 years. 

PMID- 24874223
TI  - [The role of double-ballon enteroscopy in diagnosis and treatment of polypoid
      syndromes of gastrointestinal tract].
AB  - It was done 192 double-ballon enteroscopies in 141 patients at the period from
      March 2009 to March 2012. Epithelial benign tumors were detected in 10 (7.1%)
      patients with congenital polypoid syndromes. Endoscopic excision of polyps was
      done in 6 patients including 1 case with laparoscopic-assisted technique. Urgent
      open surgeries were performed before this in 4 patients with Peutz-Jeghers'
      syndrome and invaginated small bowel obstruction. The authors consider that
      double-ballon enteroscopy is highly informative diagnostic and treatment method
      in case of small bowel diseases. It allows to diagnose and to treat epithelial
      tumors on the early stage. Also it could help to avoid complications development
      and disability of patients. 

PMID- 24874224
TI  - [The current place of abdomino-anal pull-through resection of the rectum in the
      modern rectal cancer surgery].
AB  - It was discussed abdomino-anal resection of rectum with relegation of colon
      excess in anal canal in case of cancer. It was presented the data about state of
      colo-anal functions in patients after such operations. The reasons of
      unsatisfactory functional results are analyzed in the article. Also it was
      described the factors influencing on violation of tank, evacuation and obturator
      functions. 

PMID- 24874225
TI  - [Tactics of surgical treatment of degenerative-dystrophic lesions of the
      lumbosacral spine in case of HIP-SPINE-syndrome].
AB  - The objective of this study is definition of surgical treatment tactics of
      multilevel degenerative-dystrophic lesions of the lumbosacral spine in case of
      HIP-SPINE-syndrome. It was presented the experience of surgical treatment of
      multilevel degenerative-dystrophic lesions of the lumbosacral spine in 52
      patients aged from 48 to 81 years. Lumbar stenosis prevailed in 38 (73.1%) cases.
      There was degenerative spondylolisthesis in 9 (17.3%) cases, and degenerative
      scoliosis was detected in 5 (9.6%) patients. Different types of decompressive
      stabilizing interventions according to direction of compression and the presence
      of degenerative instability were performed in all patients. Evaluation of
      surgical treatment was done by using of visual analog scale and questionnaire
      Oswestry Disability Index. It was revealed significant improvement of life
      quality by reducing of pain and increasing of daily activity. Maximal time of
      observation was 36 months. 

PMID- 24874226
TI  - [Peculiarities of surgical care in case of open injuries of limbs in emergency
      situations in peacetime].
AB  - It was done the comparative analysis of treatment results of casualties with open
      injuries of limbs in emergency situations in peacetime. It was determined that
      traditional approach of field surgery is unacceptable for this group of
      casualties. It is connected with limitations of evacuation and high frequency of
      complications. The developed modified surgical protocol permits not only to
      provide specialized care to casualties with soft tissue trauma and open fracture
      of limbs but also to reduce frequency of deep suppuration in 1.9 times. Also it
      allows to decrease number of dressings for one patient and period of the wound
      defect preparation to reconstructive plastic surgeries in 2.6 and 1.5 times
      respectively. 

PMID- 24874227
TI  - [Purulent thoracic complications treatment in elderly patient after Crawford's
      surgery].

PMID- 24874228
TI  - Antiproliferative activity of the Michael adducts of aroylacrylic acids and
      cyclic amines.
AB  - Antiproliferative activity of twenty one Michael adducts of aroylacrylic acids
      and cyclic amines (N-Me-piperazine, imidazole, 2-Me-imidazole, and indole) was
      tested toward five human tumor cell lines (HeLa, LS174, K562, FemX, MDA-MB-361)
      in vitro. Compounds exerted antiproliferative activity in the high to the single
      digit micromolar concentrations, causing increase of the cell population fraction
      in S phase and apoptosis. N-Me-piperazine and imidazole derivatives of
      aroylacrylic acids substituted with bulky alkyl substituents (2,4-di-i-Pr-Ph-,
      2,4,6-tri-Et-Ph-, or beta-tetrahydronaphthyl-) showed the best potency, while
      indole adducts were proved as the inferior antiproliferative agents. Few
      compounds showed significant selectivity, tumor versus healthy cells, with
      selectivity index ~60 for the most selective congener. An unbiased in silico
      distinction between more and less potent compounds was obtained from 3D QSAR
      models derived by alignment-independent GRIND-2 descriptors.

PMID- 24874229
TI  - Objective assessment of endogenous collagen in vivo during tissue repair by laser
      induced fluorescence.
AB  - Collagen, a triple helical protein with the primary role of mechanical function,
      provides tensile strength to the skin, and plays a pivotal task in tissue repair.
      During tissue regeneration, collagen level increases gradually and therefore,
      monitoring of such changes in vivo by laser induced fluorescence was the main
      objective behind the present study. In order to accomplish this, 15 mm diameter
      excisional wounds were created on six to eight week old Swiss albino mice. The
      collagen deposition accelerated upon irradiation of single exposure of 2 J/cm2 He
      Ne laser dose immediately after wounding was recorded by laser induced
      autofluorescence in vivo along with un-illuminated and un-wounded controls.
      Autofluorescence spectra were recorded for each animal of the experimental groups
      on 0, 5, 10, 30, 45 and 60 days post-wounding, by exciting the granulation
      tissue/skin with 325 nm He-Cd laser. The variations in the average collagen
      intensities from the granulation tissue/skin of mice were inspected as a function
      of age and gender. Further, the spectral findings of the collagen synthesis in
      wound granulation tissue/un-wounded skin tissues were validated by Picro-Sirius
      red- polarized light microscopy in a blinded manner through image analysis of the
      respective collagen birefringence. The in vivo autofluorescence studies have
      shown a significant increase in collagen synthesis in laser treated animals as
      compared to the un-illuminated controls. Image analysis of the collagen
      birefringence further authenticated the ability of autofluorescence in the
      objective monitoring of collagen in vivo. Our results clearly demonstrate the
      potential of laser induced autofluorescence in the monitoring of collegen
      synthesis during tissue regeneration, which may have clinical implications. 

PMID- 24874230
TI  - Dietary supplementation of zinc nanoparticles and its influence on biology,
      physiology and immune responses of the freshwater prawn, Macrobrachium
      rosenbergii.
AB  - The present study was conducted to assess the influence of dietary zinc
      nanoparticles (size 50 nm) on the growth, biochemical constituents, enzymatic
      antioxidant levels and the nonspecific immune response of the freshwater prawn,
      Macrobrachium rosenbergii post larvae (PL). The concentrations of dietary
      supplement zinc nanoparticles (ZnNPs) were 0, 10, 20, 40, 60 and 80 mg kg(-1)
      with the basal diet, and the level of Zn in ZnNP-supplemented diets were 0.71,
      10.61, 20.73, 40.73, 60.61 and 80.60 mg kg(-1), respectively. ZnNP-incorporated
      diets were fed to M. rosenbergii PL (initial body weight, 0.18 +/- 0.02 g) in a
      triplicate experimental setup for a period of 90 days. ZnNP supplemented feed fed
      PL up to 60 mg kg(-1) showed significantly (P < 0.05) improved performance in
      survival, growth and activities of digestive enzymes (protease, amylase and
      lipase). The concentrations of biochemical constituents (total protein, total
      amino acid, total carbohydrate and total lipid), total haemocyte count and
      differential haemocyte count were elevated in 10-60 mg kg(-1) ZnNP supplemented
      feed fed PL. However, the PL fed with 80 mg ZnNPs kg(-1) showed negative results.
      Activities of enzymatic antioxidants [superoxide dismutase (SOD) and catalase
      (CAT)], metabolic enzymes [glutamate-oxaloacetate transaminase (GOT) and
      glutamate-pyruvate transaminase (GPT)] and the process of lipid peroxidation
      (LPO) in the hepatopancreas and muscle showed no significant alterations in 10-60
      mg kg(-1) ZnNP supplemented feed fed PL. Whereas, 80 mg ZnNPs kg(-1) supplemented
      feed fed PL showed significant elevations in SOD, CAT, LPO, GOT and GPT.
      Therefore, 80 mg ZnNPs kg(-1) was found to be toxic to M. rosenbergii PL. Thus,
      the study suggests that up to 60 mg ZnNPs kg(-1) can be supplemented for
      regulating survival, growth and immunity of M. rosenbergii.

PMID- 24874232
TI  - Managing and monitoring human impacts on landscapes for environmental change and
      sustainability.

PMID- 24874233
TI  - Reprint of: The evil of sluits: a re-assessment of soil erosion in the Karoo of
      South Africa as portrayed in century-old sources.
AB  - Deep, linear gullies are a common feature of the present landscape of the Karoo
      of South Africa, where they were known locally in the early twentieth century as
      'sluits'. Recent research has shown that many of these features are now stable
      and are no longer significant sediment sources, although they are efficient
      connectors in the landscape. Because most of the gully networks predate the first
      aerial photographs, little is known in the scientific literature about the timing
      of their formation. One secondary source, however, throws interesting light on
      the origin of these features, and the early response by landowners to their
      rehabilitation. The Agricultural Journal of the Cape of Good Hope at the turn of
      the Twentieth Century carried a number of articles by farmers and agricultural
      officers concerning the "evil of sluits". The authors gave accounts of widespread
      incision of valley bottoms by deep, wide gullies. Many of these gullies had been
      in existence for some thirty years but apparently had formed within living
      memory. A number of attempts to prevent further erosion had been put in place at
      the time of writing. This paper presents a review of land degradation,
      specifically gully erosion, and rehabilitation recommendations as given by
      authors writing in this journal. It reflects on the findings in the context of
      assessing land degradation processes through the local knowledge portrayed in the
      journal.

PMID- 24874234
TI  - The influence of neurite-inducing agents on cholinergic activity in human
      neuroblastoma cells.
AB  - Various factors capable of inducing morphological differentiation of
      neuroblastoma cells were studied to determine whether they may also specifically
      regulate cholinergic function in human cholinergic neuroblastoma cells MC-IXC.
      Choline acetyltransferase (CAT) activity was monitored to reflect cholinergic
      function while Mg(2+) ATPase activity was monitored to reflect effects which are
      not related specifically to neuronal function. Among the agents,
      dimethylsulfoxide (DMSO), dimethylformamide (DMF), dimethylacetamide (DMA), D
      alpha-tocopherol, ascorbic acid and dibutyryl-cAMP, only low doses of DMSO were
      found to selectively inhibit CAT activity while Mg(2+) ATPase activity along with
      population growth remained unaffected. Of the three chemically related organic
      compounds tested (DMSO, DMF, DMA), DMSO was the least potent with regard to
      inhibition of population growth and Mg(2+) ATPase activity while DMA was the most
      potent inhibitor. Sodium butyrate caused a decline in CAT activity while retinoic
      acid induced an enhancement. The combination of sodium butyrate with retinoic
      acid caused an enhancement of CAT activity similar in magnitude to that observed
      with retinoic acid alone. Lastly, CAT activity was found to be independent of
      population density unlike that in different neuroblastoma cell lines.(8,12,19.) 

PMID- 24874235
TI  - Monoamine concentrations in brain regions of the developing rabbit.
AB  - Growth patterns in selected areas of rabbit brain were studied neurochemically by
      assaying for norepinephrine, dopamine and serotonin from the neonatal to adult
      stages of development. These measurements showed that the various monoamines
      reached adult concentrations at different rates within a brain region; each
      region had a unique pattern of amine development. Changes in content were most
      marked in the first 2 weeks of life. Concentration increases were pronounced for
      norepinephrine and serotonin in the hypothalamus and for dopamine in the caudate
      nucleus. By contrast, norepinephrine concentrations in the pons-medulla and
      colliculi were relatively stable. The marked changes and differences in amine
      concentrations of maturing rabbit brain provide basic data on monoaminergic
      innervation of discrete regions and indicate the rabbit merits consideration in
      neurochemical and physiologic studies on the development of neurotransmission. 

PMID- 24874236
TI  - Effects of NaCl and sultopride on striatal [(3)H]spiperone binding in neonatal,
      adult and senescent rats.
AB  - Effects of NaCl, (+)-and (-)-sultopride on striatal [(3)H]spiperone binding was
      investigated in 7-day, 70-day and 2-year-old rats. The amount of specific
      [(3)H]spiperone binding was the highest at 70 days and the value at adult stage
      was significantly (P < 0.001) higher than those at 7 days and 2 years. NaCl (100
      mM) significantly increased [(3)H]spiperone binding in neonatal (P < 0.01), adult
      (P < 0.05) and senescent (P < 0.05) animals. Scatchard analysis showed that the
      Bmax of low-affinity [(3)H]spiperone binding was significantly elevated by 100 mM
      NaCl compared to the value in control of adult animals. More potent inhibition of
      (-)-sultopride for [(3)H]spiperone binding than that of the (+)-enantiomer at
      adult stage was also observed at neonatal and senescent stages. NaCl (100 mM)
      significantly enhanced inhibitory activities of (+)- and (-)-sultopride at every
      stage. It is suggested that stabilizing effect of Na(+) on dopamine (DA) receptor
      complexes and increasing effect of Na(+) on binding affinity of benzamide to DA2
      receptors keep functions through development and aging. 

PMID- 24874231
TI  - LlHSFA1, a novel heat stress transcription factor in lily (Lilium longiflorum),
      can interact with LlHSFA2 and enhance the thermotolerance of transgenic
      Arabidopsis thaliana.
AB  - KEY MESSAGE: A heat stress transcription factor LlHSFA1 in lily and its
      relationship with LlHSFA2 was investigated, and its function in enhancing
      thermotolerance was confirmed by analyzing transgenic Arabidopsis thaliana
      overexpressed LlHSFA1. A large family of heat stress transcription factors that
      are involved in the heat stress response in plants can induce the expression of
      multiple genes related to thermotolerance including heat-shock proteins. In this
      study, a novel class A1 HSF named LlHSFA1 was isolated from leaves of lily
      (Lilium longiflorum cv. 'White Heaven') using the rapid amplification of cDNA
      ends technique. Analysis of the deduced amino acid sequence and construction of a
      phylogenetic tree showed that LlHSFA1 contained five critical domains and motifs
      and belonged to the A1 family of HSFs. Following the heat treatment of lily
      leaves, transcription of LlHSFA1 was induced to a varying extent, related to the
      time of measurement. The induced expression peak of LlHSFA1 occurred prior to
      that of LlHSFA2, during the early phase of heat stress. Following transient
      expression of LlHSFA1 in Nicotiana benthamiana, LlHSFA1 was found to be localized
      in both the nucleus and the cytoplasm. Analysis using bimolecular fluorescence
      complementation and a yeast two-hybrid assay demonstrated that LlHSFA1 could
      interact with LlHSFA2. Use of a yeast one-hybrid assay confirmed that LlHSFA1 had
      transcriptional activation activity. In transgenic Arabidopsis lines
      overexpressing LlHSFA1 under unstressed conditions, the expression of some
      putative target genes was up-regulated, in comparison with expression in wild
      type plants, and furthermore, the thermotolerance of the transgenic lines was
      enhanced. Overall, LlHSFA1 was demonstrated to play an important role in the heat
      stress response of lily and to be a novel candidate gene for application in lily
      breeding, using genetic modification approaches.

PMID- 24874237
TI  - In Purkinje cell dendrites of the young rat, thyroid hormone controls the
      resistance of microtubules to fixation at low temperature.
AB  - Microtubules were studied in parallel fibres and Purkinje cell dendrites of 14
      day-old normal and propylthiouracil-treated rats after fixation of the cerebellum
      at room and low temperature (4 degrees C). In both control and propylthiouracil
      treated animals, nearly all the microtubules of parallel fibres disappeared after
      fixation at low temperature. In Purkinje cell dendrites of control animals, 60%
      of the microtubules persisted at low temperature. Propylthiouracil treatment led
      to a 78% decrease in the density of these cold-stable microtubules. In contrast,
      the density of cold-labile microtubules remained normal. Administration of low
      doses of thyroxine to the propylthiouracil-treated rats produced a rapid increase
      in the density of cold-labile microtubules, but long-term treatment with the
      hormone was necessary to obtain normal density of cold-stable microtubules.
      Thyroid hormone thus seems to regulate some properties of microtubules involved
      in their resistance to fixation at low temperature. These properties could be of
      importance in growth and branching of dendrites. 

PMID- 24874238
TI  - Reductions in the plating efficiency of the fetal neural precursor cells
      following maternal alcohol consumption.
AB  - Maternal alcohol abuse has been associated with reduced neural cell number and
      abnormal cell differentiation and organization in many regions of the developing
      mammalian brain. Experiments were conducted to determine whether changes in the
      neural precursor cells could be detected in primary culture following maternal
      alcohol consumption during the early proliferative period of the fetal brain
      growth spurt. Alcohol was administered to pregnant mice in the drinking water
      from days 11 to 19 of gestation. There was no alcohol-related increase in the
      incidence of fetal mortality or malformation, but fetal body and brain weights
      were reduced. When disaggregated cells from the day 19 fetal neopallium were
      grown in culture, there was a reduction in the number of astroglial colonies
      yielded in 42% of alcohol-exposed brains. This effect was expressed as a
      reduction in the absolute plating efficiency (APE) of the neural precursor cells.
      The APE was reduced as much as 80% in severely affected brains. There was no
      alcoholrelated difference in the in vitro morphogenesis of the astroglial
      colonies. Observations of the proliferative neural cells in situ suggest that
      there is an impaired recruitment of all neural cell types, but that the reduced
      APE reflects primarily a proportionate increase in the number of immature neurons
      among the cells obtained from the fetal neopallium. It appears that a
      prolongation of mitosis may be resulting in a general developmental delay in the
      fetal neocortex. 

PMID- 24874239
TI  - Long-chain acyl coenzyme A synthetase activity during the postnatal development
      of the mouse brain.
AB  - Palmitic, linoleic, arachidonic, and docosahexaenoic acids were used as
      substrates to study fatty acid activation in the mouse brain and liver during
      postnatal development. Long-chain acyl coenzyme A synthetase showed peak activity
      during the period of rapid oligodendroglial proliferation and myelination. In
      brain, activation of linoleic and arachidonic acids was highest, followed by
      palmitic and docosahexaenoic acids. In liver, no appreciable change in enzyme
      activity was seen during the period of development studied. Palmitic and
      arachidonic acids showed the highest rate of activation, followed by
      docosahexaenoic acid. These ontogenic data suggest the presence of a single long
      chain acyl coenzyme A synthetase in brain. 

PMID- 24874240
TI  - Development of substance P-immunoreactive neurons in cranial sensory ganglia of
      the rat.
AB  - Substance P-like immunoreactivity has been observed in fetal and adult cranial
      sensory ganglia. It first appears at day 16 of gestation in sensory neurons of
      trigeminal, superior-jugular, petrous and nodose ganglia, as well as in the
      autonomic myenteric plexus, and at day 17 in cervical dorsal root ganglion cells.
      Substance P immunoreactivity can be visualized much earlier (day 12) in the
      central nervous system. The ganglionic immunoreactivity subsequently increases
      during fetal life but drops at birth. The reactive material is first diffuse,
      then slowly becomes granular, and is mostly concentrated in coarse perinuclear
      inclusions in adult sensory neurons. Most substance P-positive neurons in
      trigeminal and superior-jugular ganglia are small, but medium-sized and large
      positive neurons are also observed in the trigeminal, petrous and nodose ganglia.
      Our observations give a precise picture of the development of substance P
      immunoreactivity in sensory neurons and are in general agreement with previous
      reports on some fetal and adult rat sensory ganglia. They indicate that in the
      rat, maturation of peripheral substance P-containing sensory neurons is slower
      than that of central substance P neurons or equivalent sensory neurons in other
      species. The examination of fetal material allows the observation of numerous
      immunoreactive sensory neurons which cannot be visualized after birth. We
      hypothesize a possible different embryonic origin (neural crest or placodal) for
      small nociceptive and larger substance P-containing neurons in rat cranial
      sensory ganglia. 

PMID- 24874241
TI  - Comparison of taurine, hypotaurine and beta-alanine uptake in brain synaptosomal
      preparations from developing and adult mouse.
AB  - The properties of taurine, hypotaurine and beta-alanine uptakes were compared in
      brain synaptosomal preparations from 6-day-old and adult mice. The uptakes of
      these structurally related amino acids resembled each other, being concentrative,
      sodium-dependent and inhibited by the same analogues. The absolute sodium
      requirement of uptake was already evident in developing brain. The affinity of
      the lowaffinity uptake for taurine was higher in immature than in adult brain.
      Both affinity and maximal velocity increased in hypotaurine uptake during
      development, whereas in beta-alanine uptake only the maximal velocity did so. The
      efficient synaptosomal taurine and hypotaurine transport systems in immature
      brain could contribute to the high taurine level in developing brain. 

PMID- 24874242
TI  - Differentiation of neurons and radial glia in the spinal cord of the teleost
      Brachydanio rerio (the zebrafish): An immunocytochemical study.
AB  - The differentiation of neurons and glial cells in the spinal cord of the
      zebrafish was studied by means of immunohistochemistry, using antisera against
      the 68 kD subunit of neurofilament (anti-NFP68) and against glial fibrillary
      acidic protein (anti-GFAP), both isolated from the bovine brain. Anti-NFP68 and
      anti-GFAP reactivity appear in the spinal cord at about 60 h after fertilization.
      At that time the anti-NFP68 reactivity is detectable in the dorsal Rohon-Beard
      neurons. About 12 h later, NFP68 positive neurons appear in the prospective motor
      column. In this respect the differentiation of the primary sensory system
      precedes that of the spinal motor system. During development the configuration of
      the glial cell processes changes from a horizontal arrangement in embryos to a
      radial frame work in larvae and in adults. From these observations together with
      data on the organization of the adult spinal motor column(28) we conclude that
      the motoneurons of the white and those of the red myotomal muscle fibers may have
      different origins in the neuroepithelial germinal layer. The anti-NFP68 serum
      recognizes a 120 and a 94 kD component of fish neurofilaments. Thus the subunit
      composition of neurofilament in fishes differs from that in mammals. 

PMID- 24874244
TI  - Dopamine-beta-hydroxylase-like immunoreactivity in the fetal cerebral cortex of
      the rat: Noradrenergic ascending pathways and terminal fields.
AB  - A topographical analysis of the noradrenergic innervation in the fetal rat
      cerebral cortex was carried out from embryonic day 15 (E15) until birth using
      antibodies raised against dopamine-beta-hydroxylase (DBH). During late gestation
      DBH-like immunoreactive axons were coursing through the basal forebrain along
      three pathways: The first noradrenergic axons were seen at E17 in the frontal
      pole, the lateral frontal cortex, and in the medial frontal cortex which also
      receives a dopaminergic input. The innervation then extended caudally, but the
      dorsal part of the cortex was reached after a 2-day delay when compared to the
      medial and lateral parts. The arrival of noradrenergic axons did not parallel the
      gradient of cortical neurogenesis; however, all cortical areas were innervated at
      birth. DBH positive fibers reached a given cortical region simultaneously through
      the marginal and intermediate zones and then invaded the cortical plate. 

PMID- 24874243
TI  - Some electrophysiological properties of developing rat skeletal myotubes grown in
      serum-free, chemically defined medium.
AB  - Serum-free, chemically defined media have been reported to provide suitable
      conditions for growth and proliferation of mammalian skeletal muscle, but there
      is no information regarding the ability of myotubes to develop normal
      electrophysiological properties in these media. We have recorded transmembrane
      resting and action potentials from rat skeletal myotubes grown in both serum
      containing (GM) and serum-free chemically defined (CDM) growth media. Muscle
      cells in CDM do not develop as high resting Em as their counterparts in
      conventional growth media. CDM myotubes also had a lower incidence and frequency
      of spontaneously occurring action potentials. Treatment with ouabain or decrease
      in temperature of the recording medium reduced resting Em of both GM and CDM
      cells to the same level. We found that the sensitivity of CDM cells to ouabain
      was about 10-fold higher than that of GM cells. An increase in temperature of the
      recording medium increased Em of GM myotubes but not of CDM myotubes. The change
      in resting Em in response to a 10-fold change in extracellular K(+)-ion
      concentration was the same for both groups of cells thus indicating that there
      was no difference in membrane permeability to K(+)-ion. We conclude that the
      difference in Em can be accounted for largely, if not entirely, by differences in
      activity or amount of electrogenic Na(+)-K(+) ATPase. 

PMID- 24874245
TI  - Targeting human equilibrative nucleoside analog transporter (hENT1) expression
      through modified low glycemic index diet in pancreatic cancer.
AB  - Pancreatic cancer is a highly aggressive and chemotherapy-resistant cancer. Up to
      date, the primary goals of nutrition interventions for pancreatic cancer'
      patients are to prevent or reverse loss of weight and malnutrition in order to
      maintain dose and schedule of cancer treatments and/or to manage symptoms due to
      the lack of enzymes' production by the damaged pancreas. With this script, we
      sought to underline the potential link between dietary settings and the
      modulation of chemoresistance in pancreatic cancer. 

PMID- 24874246
TI  - Adding isotretinoin to lithium carbonate probably caused mild lithium toxicity.

PMID- 24874247
TI  - Classifying teenage depression.

PMID- 24874249
TI  - Brief report #2: the caregiver ombudsman outreach program (co-op): lessons
      learned for engaging students and impacting the community.
AB  - We discuss a program designed collaboratively by eight community-based agencies
      and a school of social work to serve ethnically-diverse caregivers of older
      adults in an under-resourced area of New York City. The program offered
      comprehensive assessments, referrals and information, and respite care to
      maximize use of existing resources and build a stronger web of support for
      caregivers. Social work and nursing students participated in all aspects of the
      project, including development, implementation, and evaluation. This level of
      involvement facilitates a deep understanding of the interconnections among
      practice, research, policy, and education, and fosters an interest in and
      commitment to working with older adults and their families. 

PMID- 24874248
TI  - Preserved autonomic heart rate modulation in chronic renal failure patients in
      response to hemodialysis and orthostatism.
AB  - BACKGROUND: The aim of this work was to measure the impact of active orthostatism
      and hemodialysis (HD) upon heart rate variability (HRV) in chronic renal failure
      (CRF) patients before and after HD. METHODS: Nineteen healthy subjects (age 27 +/
      8 years old, 13 were female) and 19 unmedicated CRF patients with HD thrice per
      week (average HD vintage = 12 months, age 32 +/- 9 years old, 11 were female)
      were included. Five-minute length HRV time series were obtained during supine
      position and orthostatism. Recordings from CRF patients were obtained before and
      after HD. Time domain and frequency domain HRV indexes were compared by analysis
      of variance. The correlation between each HRV index and change in sympathetic
      weighting induced by different maneuvers was tested by Kendall's Tau correlation.
      A p value <0.05 was considered statistically significant. RESULTS: HRV indexes
      which are associated with sympathetic activity increased in response to
      orthostatism in the healthy group, e.g., low-frequency to high-frequency (LF/HF)
      ratio, Ln (LF/HF) = -0.3 +/- 0.9 versus 0.9 +/- 0.9. CRF patients before HD had
      higher sympathetic weighting than healthy participants, even in supine position,
      Ln (LF/HF) = 0.6 +/- 1.0, but such a difference was accentuated during
      orthostatism, Ln (LF/HF) = 1.5 +/- 1.0, and after HD: Ln (LF/HF) = 0.8 +/- 1.3
      (supine position) and 2.5 +/- 2.1 (orthostatism). All HRV indexes were associated
      with increments in sympathetic weighting between maneuvers (Kendall's
      correlations absolute values >= 0.24). CONCLUSION: Unmedicated young CRF patients
      treated with hemodynamically stable maintenance HD showed preserved capacity of
      autonomic response (with gradual sympathetic increases) induced by cardiovascular
      challenges such as orthostatism and HD.

PMID- 24874250
TI  - [Chronic epicarditis, a soft pericardial constriction: about one case].
AB  - Chronic constrictive epicarditis is a special form of chronic pericarditis. It is
      characterized by a thickening of the visceral pericardium that becomes adherent
      to cardiovascular structures, thus impeding the diastolic filling of the
      ventricles. The parietal pericardium remains soft, without symphysis with the
      visceral pericardium. We illustrate the diagnostic and therapeutic approaches to
      this pathology by a clinical case. 

PMID- 24874251
TI  - [Emergent transcatheter aortic valve implantation in a patient with bicuspid
      aortic valve stenosis in cardiogenic shock].
AB  - Transcatheter aortic valve implantation is a therapeutic option for high-risk
      patients with severe aortic valve stenosis and with cardiac symptoms. This
      procedure requires the preliminary evaluation by a "heart team" and presents some
      contraindications. We report the case of a 58-year-old man with severe bicuspid
      aortic valve stenosis and cardiogenic shock. In spite of contraindications and
      because of the failure of balloon aortic valvuloplasty, transcatheter aortic
      valve implantation was performed in emergency. 

PMID- 24874252
TI  - Safety evaluation of high-dose BCNU-loaded biodegradable implants in Chinese
      patients with recurrent malignant gliomas.
AB  - OBJECTIVES: Malignant gliomas are common primary brain tumors with dismal
      prognosis. The blood-brain barrier and unacceptable systemic toxicity limit the
      employment of chemotherapeutic agents. BCNU-impregnated biodegradable polymers
      (Gliadel(r)) have been demonstrated to prolong the survival of patients with
      malignant gliomas. Until now, no biodegradable drug delivery system has been
      commercially available in China. In the present study, we evaluated the safety of
      implants with high-dose BCNU in Chinese patients with recurrent malignant
      gliomas. PATIENTS AND METHODS: Adults with supratentorial recurrent malignant
      glioma were eligible. High-dose BCNU-loaded PLGA implants (20mg of BCNU in each
      implant) were placed in the debulking cavity. The implants were investigated by a
      classical 3+3 design. Four levels of BCNU, up to 12 implants, were evaluated.
      Pharmacokinetic sampling was performed. The toxicity of the implants and the
      survival of patients were recorded. RESULTS: Fifteen recurrent patients were
      enrolled with 12 glioblastomas and 3 anaplastic gliomas. Among 15 patients, 3
      were treated with 3 implants (60 mg of BCNU), 3 with 6 implants (120 mg), 3 with
      9 implants (180 mg) and 6 with 12 implants (240 mg). No dose-limiting toxicity
      was observed in the cohort of patients. Subgaleal effusion was the most common
      adverse event, presenting in 7 patients (46.7%). The median overall survival (OS)
      was 322 days (95% CI, 173-471 days). The 6-month, 1-year and 2-year survival
      rates were 66.7%, 40% and 13.3%, respectively. CONCLUSIONS: The high-dose BCNU
      loaded PLGA implants were safe for Chinese patients with recurrent malignant
      gliomas and further investigation for efficacy is warranted.

PMID- 24874257
TI  - Perceptual hysteresis in the judgment of auditory pitch shift.
AB  - Perceptual hysteresis can be defined as the enduring influence of the recent past
      on current perception. Here, hysteresis was investigated in a basic auditory
      task: pitch comparisons between successive tones. On each trial, listeners were
      presented with pairs of tones and asked to report the direction of subjective
      pitch shift, as either "up" or "down." All tones were complexes known as Shepard
      tones (Shepard, 1964), which comprise several frequency components at octave
      multiples of a base frequency. The results showed that perceptual judgments were
      determined both by stimulus-related factors (the interval ratio between the base
      frequencies within a pair) and by recent context (the intervals in the two
      previous trials). When tones were presented in ordered sequences, for which the
      frequency interval between tones was varied in a progressive manner, strong
      hysteresis was found. In particular, ambiguous stimuli that led to equal
      probabilities of "up" and "down" responses within a randomized context were
      almost fully determined within an ordered context. Moreover, hysteresis did not
      act on the direction of the reported pitch shift, but rather on the perceptual
      representation of each tone. Thus, hysteresis could be observed within sequences
      in which listeners varied between "up" and "down" responses, enabling us to
      largely rule out confounds related to response bias. The strength of the
      perceptual hysteresis observed suggests that the ongoing context may have a
      substantial influence on fundamental aspects of auditory perception, such as how
      we perceive the changes in pitch between successive sounds. 

PMID- 24874258
TI  - Focused attention improves working memory: implications for flexible-resource and
      discrete-capacity models.
AB  - Performance in working memory (WM) tasks depends on the capacity for storing
      objects and on the allocation of attention to these objects. Here, we explored
      how capacity models need to be augmented to account for the benefit of focusing
      attention on the target of recall. Participants encoded six colored disks
      (Experiment 1) or a set of one to eight colored disks (Experiment 2) and were
      cued to recall the color of a target on a color wheel. In the no-delay condition,
      the recall-cue was presented after a 1,000-ms retention interval, and
      participants could report the retrieved color immediately. In the delay
      condition, the recall-cue was presented at the same time as in the no-delay
      condition, but the opportunity to report the color was delayed. During this
      delay, participants could focus attention exclusively on the target. Responses
      deviated less from the target's color in the delay than in the no-delay
      condition. Mixture modeling assigned this benefit to a reduction in guessing
      (Experiments 1 and 2) and transposition errors (Experiment 2). We tested several
      computational models implementing flexible or discrete capacity allocation,
      aiming to explain both the effect of set size, reflecting the limited capacity of
      WM, and the effect of delay, reflecting the role of attention to WM
      representations. Both models fit the data better when a spatially graded source
      of transposition error is added to its assumptions. The benefits of focusing
      attention could be explained by allocating to this object a higher proportion of
      the capacity to represent color. 

PMID- 24874253
TI  - A new tool to quantify receptor recruitment to cell contact sites during host
      pathogen interaction.
AB  - To understand the process of innate immune fungal recognition, we developed
      computational tools for the rigorous quantification and comparison of receptor
      recruitment and distribution at cell-cell contact sites. We used these tools to
      quantify pattern recognition receptor spatiotemporal distributions in contacts
      between primary human dendritic cells and the fungal pathogens C. albicans, C.
      parapsilosis and the environmental yeast S. cerevisiae, imaged using 3D
      multichannel laser scanning confocal microscopy. The detailed quantitative
      analysis of contact sites shows that, despite considerable biochemical similarity
      in the composition and structure of these species' cell walls, the receptor
      spatiotemporal distribution in host-microbe contact sites varies significantly
      between these yeasts. Our findings suggest a model where innate immune cells
      discriminate fungal microorganisms based on differential mobilization and
      coordination of receptor networks. Our analysis methods are also broadly
      applicable to a range of cell-cell interactions central to many biological
      problems. 

PMID- 24874259
TI  - The effects of saccade-contingent changes on oculomotor capture: salience is
      important even beyond the first oculomotor response.
AB  - Whenever a novel scene is presented, visual salience merely plays a transient
      role in oculomotor selection. Unique stimulus properties, such as a distinct and,
      thereby, salient color, affect the oculomotor response only when observers react
      relatively quickly. For slower responses, or for consecutive ones, salience
      driven effects appear completely absent. To date, however, the circumstances that
      may reinstate the effects of salience over multiple eye movements are still
      unclear. Recent research shows that changes to a scene can attract gaze, even
      when these changes occur without a transient signal (i.e., during an eye
      movement). The aim of the present study was to investigate whether this capture
      is mediated through salience-driven or memory-guided processes. In three
      experiments, we examined how the nature of a change in salience that occurred
      during an eye movement affected consecutive saccades. The results demonstrate
      that the oculomotor system is exclusively susceptible to increases in salience
      from one fixation to the next, but only when these increases result in a uniquely
      high salience level. This suggests that even in the case of a saccade-contingent
      change, oculomotor selection behavior can be affected by salience-driven
      mechanisms, possibly to allow the automatic detection of uniquely distinct
      objects at any moment. The results and implications will be discussed in relation
      to current views on visual selection. 

PMID- 24874260
TI  - Hemifield asymmetries differentiate VSTM for single- and multiple-feature
      objects.
AB  - Visual short-term memory (VSTM) is a capacity-limited system for maintaining
      visual information across brief durations. Limits in the amount of information
      held in memory reflect processing constraints in the intraparietal sulcus (IPS),
      a region of the frontoparietal network also involved in visual attention. During
      VSTM and visual attention, areas of IPS demonstrate hemispheric asymmetries.
      Whereas the left hemisphere represents information in only the right hemifield,
      the right hemisphere represents information across the visual field. In visual
      attention, hemispheric asymmetries are associated with differences in behavioral
      performance across the visual field. In order to assess the degree of hemifield
      asymmetries in VSTM, we measured memory performance across the visual field for
      both single- and two-feature objects. Consistent with theories of right
      hemisphere dominance, there was a memory benefit for single-feature items in the
      left visual hemifield. However, when the number of features increased, the
      behavioral bias reversed, demonstrating a benefit for remembering two-feature
      objects in the right hemifield. On an individual basis, the cost of remembering
      an additional feature in the hemifields was correlated, suggesting that the shift
      in hemifield biases reflected a redistribution of resources across the visual
      field. Furthermore, we demonstrate that these results cannot be explained by
      differences in perceptual or decision-making load. Our results are consistent
      with a flexible resource model of VSTM in which attention and/or working memory
      demands result in representation of items in the right hemifield by both the left
      and right hemispheres. 

PMID- 24874261
TI  - Acquisition process of typing skill using hierarchical materials in the Japanese
      language.
AB  - In the present study, using a new keyboard layout with only eight keys, we
      conducted typing training for unskilled typists. In this task, Japanese college
      students received training in typing words consisting of a pair of hiragana
      characters with four keystrokes, using the alphabetic input method, while keeping
      the association between the keys and typists' finger movements; the task was
      constructed so that chunking was readily available. We manipulated the
      association between the hiragana characters and alphabet letters (hierarchical
      materials: overlapped and nonoverlapped mappings). Our alphabet letter materials
      corresponded to the regular order within each hiragana word (within the four
      letters, the first and third referred to consonants, and the second and fourth
      referred to vowels). Only the interkeystroke intervals involved in the initiation
      of typing vowel letters showed an overlapping effect, which revealed that the
      effect was markedly large only during the early period of skill development (the
      effect for the overlapped mapping being larger than that for the nonoverlapped
      mapping), but that it had diminished by the time of late training. Conversely,
      the response time and the third interkeystroke interval, which are both involved
      in the latency of typing a consonant letter, did not reveal an overlapped effect,
      suggesting that chunking might be useful with hiragana characters rather than
      hiragana words. These results are discussed in terms of the fan effect and skill
      acquisition. Furthermore, we discuss whether there is a need for further research
      on unskilled and skilled Japanese typists. 

PMID- 24874262
TI  - The role of head movements in the discrimination of 2-D shape by blind
      echolocation experts.
AB  - Similar to certain bats and dolphins, some blind humans can use sound echoes to
      perceive their silent surroundings. By producing an auditory signal (e.g., a
      tongue click) and listening to the returning echoes, these individuals can obtain
      information about their environment, such as the size, distance, and density of
      objects. Past research has also hinted at the possibility that blind individuals
      may be able to use echolocation to gather information about 2-D surface shape,
      with definite results pending. Thus, here we investigated people's ability to use
      echolocation to identify the 2-D shape (contour) of objects. We also investigated
      the role played by head movements--that is, exploratory movements of the head
      while echolocating--because anecdotal evidence suggests that head movements might
      be beneficial for shape identification. To this end, we compared the performance
      of six expert echolocators to that of ten blind nonecholocators and ten
      blindfolded sighted controls in a shape identification task, with and without
      head movements. We found that the expert echolocators could use echoes to
      determine the shapes of the objects with exceptional accuracy when they were
      allowed to make head movements, but that their performance dropped to chance
      level when they had to remain still. Neither blind nor blindfolded sighted
      controls performed above chance, regardless of head movements. Our results show
      not only that experts can use echolocation to successfully identify 2-D shape,
      but also that head movements made while echolocating are necessary for the
      correct identification of 2-D shape.

PMID- 24874263
TI  - Reward expectation influences audiovisual spatial integration.
AB  - In order to determine the spatial location of an object that is simultaneously
      seen and heard, the brain assigns higher weights to the sensory inputs that
      provide the most reliable information. For example, in the well-known
      ventriloquism effect, the perceived location of a sound is shifted toward the
      location of a concurrent but spatially misaligned visual stimulus. This
      perceptual illusion can be explained by the usually much higher spatial
      resolution of the visual system as compared to the auditory system. Recently, it
      has been demonstrated that this cross-modal binding process is not fully
      automatic, but can be modulated by emotional learning. Here we tested whether
      cross-modal binding is similarly affected by motivational factors, as exemplified
      by reward expectancy. Participants received a monetary reward for precise and
      accurate localization of brief auditory stimuli. Auditory stimuli were
      accompanied by task-irrelevant, spatially misaligned visual stimuli. Thus, the
      participants' motivational goal of maximizing their reward was put in conflict
      with the spatial bias of auditory localization induced by the ventriloquist
      situation. Crucially, the amounts of expected reward differed between the two
      hemifields. As compared to the hemifield associated with a low reward, the
      ventriloquism effect was reduced in the high-reward hemifield. This finding
      suggests that reward expectations modulate cross-modal binding processes,
      possibly mediated via cognitive control mechanisms. The motivational significance
      of the stimulus material, thus, constitutes an important factor that needs to be
      considered in the study of top-down influences on multisensory integration. 

PMID- 24874264
TI  - Same barcode, different biology: differential patterns of infectivity,
      specificity and pathogenicity in two almost identical parasite strains.
AB  - Two Norwegian isolates of the monogenean Gyrodactylus salaris Malmberg, 1957 with
      identical cytochrome c oxidase subunit I barcodes from different hosts, show
      highly divergent biological and behavioural characteristics. The Lierelva
      parasite strain, typically infecting Atlantic salmon, Salmo salar L., grew
      exponentially on Atlantic salmon, but the Palsbufjorden parasite strain, commonly
      infecting Arctic charr, Salvelinus alpinus L., grew slowly on both hosts and was
      non-pathogenic to Atlantic salmon. Both parasite strains reproduced successfully
      on Arctic charr, but the Atlantic salmon-infecting Lierelva strain grew faster on
      both hosts. Experiments with isolated worms revealed differences in reproductive
      rates which may account for the observed population differences. Atlantic salmon
      parasites consistently gave birth at an earlier age than the Arctic charr
      parasites, with the differential increasing from 1 day for the first birth up to
      2-4 days for the third birth. Arctic charr-infecting parasites were more active
      on Atlantic salmon than salmon parasites on Arctic charr, a behavioural strategy
      leading to enhanced G. salaris mortality. Sequencing of 10 kb of nuclear genomic
      markers revealed only four single nucleotide polymorphisms, confirming that
      isolates of G. salaris with differences in fitness traits influencing
      establishment, fecundity and behaviour may be remarkably similar at a molecular
      level. The framework for reporting and control of G. salaris requires re
      appraisal in light of the discovery of variants with such divergent biology.

PMID- 24874265
TI  - Structural and photophysical properties of rare-earth complexes encapsulated into
      surface modified mesoporous silica nanoparticles.
AB  - The encapsulation of [Eu(dbm)3phen] into functionalized mesoporous silica
      nanoparticles (MSN) has been carried out to study the effect of chemical
      environments on the photoluminescence properties of the rare-earth complex.
      Surface functionalization was achieved by the reaction of the silanol groups on
      the surface of mesoporous silica with different organosilylating agents such as
      (3-aminopropyl)-triethoxysilane (APTES), (3-mercaptopropyl)-trimethoxysilane
      (MPTMS), and ethoxytrimethylsilane (ETMS). A change in the luminescence
      properties of the Eu(dbm)3phen complex has been observed on its encapsulation
      into surface modified mesoporous silica nanoparticles. The modification of
      photophysical properties is attributed to the interaction of Eu(dbm)3phen with
      the different chemical environments in the functionalized mesoporous silica
      nanoparticles (MSN). The luminescence properties of the rare-earth complex in
      surface-modified MSN increase in the order MSN < MSN-ETMS < MSN-MPTMS < MSN
      APTES. The Eu(dbm)3phen complex encapsulated in the functionalized mesoporous
      silica nanoparticles shows an enhanced luminescence and an increased lifetime
      compared to the pure rare-earth complex in the solid state and that in unmodified
      MSN. This implies that some interactions of the lanthanide complexes take place
      during their incorporation process into the organically modified mesoporous
      silica nanoparticles. The organically modified mesoporous silica nanoparticles
      were characterized by Fourier transform infrared spectroscopy (FTIR) and N2
      adsorption desorption measurements. The luminescence properties of the
      encapsulated Eu(dbm)3phen were studied in detail. Moreover, the effect of
      functionalized MSNs on the structural behaviour of the Eu(dbm)3phen was
      investigated by solid state nuclear magnetic resonance (SSNMR) techniques using
      an analogous diamagnetic model complex, Y(dbm)3phen, encapsulated into
      functionalized MSNs. These studies indicate that the encapsulated rare-earth
      complex shows some interactions with the functional groups anchored on the
      surface of MSNs. 

PMID- 24874269
TI  - Sympathetic skin responses and autonomic dysfunction in spinal cord injury.
AB  - Sympathetic skin responses (SSRs), a measure of sympathetic cholinergic sudomotor
      function, have been used in the assessment of autonomic dysfunction in patients
      with spinal cord injury (SCI). This review highlights the basic mechanisms
      underlying SSRs as well as their application to the SCI population. We address
      the utility of SSRs in assessing autonomic function, the relationship between
      autonomic and sensorimotor impairment, and the association between SSRs and the
      sequelae of autonomic dysfunction in SCI, particularly autonomic dysreflexia and
      orthostatic hypotension. Overall, SSRs are a rapid, convenient and non-invasive
      method illustrating that the severity of autonomic impairment can be independent
      from sensorimotor impairment. We suggest that SSRs be used in conjunction with
      other validated autonomic tests in order to predict or document autonomic
      dysfunction in SCI.

PMID- 24874270
TI  - Syntactic networks, do they contribute valid information on syntactic development
      in children? Comment on "approaching human language with complex networks" by J.
      Cong and H. Liu.

PMID- 24874271
TI  - Dynamic connectivity and dynamic affiliation. Comment on "Understanding brain
      networks and brain organization" by L. Pessoa.

PMID- 24874273
TI  - Can higher NHS spending in deprived areas reduce health inequalities?

PMID- 24874272
TI  - A soluble adenylyl cyclase form targets to axonemes and rescues beat regulation
      in soluble adenylyl cyclase knockout mice.
AB  - Ciliary beating is important for effective mucociliary clearance. Soluble
      adenylyl cyclase (sAC) regulates ciliary beating, and a roughly 50-kD sAC variant
      is expressed in axonemes. Normal human bronchial epithelial (NHBE) cells express
      multiple sAC splice variants: full-length sAC; variants with catalytic domain 1
      (C1) deletions; and variants with partial C1. One variant, sACex5v2-ex12v2,
      contains two alternative splices creating new exons 5 (ex5v2) and 12 (ex12v2),
      encoding a roughly 45-kD protein. It is therefore similar in size to ciliary sAC.
      The variant increases in expression upon ciliogenesis during differentiation at
      the air-liquid interface. When expressed in NHBE cells, this variant was targeted
      to cilia. Exons 5v2-7 were important for ciliary targeting, whereas exons 2-4
      prevented it. In vitro, cytoplasmic sACex2-ex12v2 (containing C1 and C2) was the
      only variant producing cAMP. Ciliary sACex5v2-ex12v2 was not catalytically
      active. Airway epithelial cells isolated from wild-type mice revealed sAC
      dependent ciliary beat frequency (CBF) regulation, analogous to NHBE cells: CBF
      rescue from HCO3(-)/CO2-mediated intracellular acidification was sensitive to the
      sAC inhibitor, KH7. Compared with wild type, sAC C2 knockout (KO) mice revealed
      lower CBF baseline, and the HCO3(-)/CO2-mediated CBF decrease was not inhibited
      by KH7, confirming lack of functional sAC. Human sACex5v2-ex12v2 was targeted to
      cilia and sACex2-ex12v2 to the cytoplasm in these KO mice. Introduction of the
      ciliary sACex5v2-ex12v2 variant, but not the cytoplasmic sACex2-ex12v2, restored
      functional sAC activity in C2 KO mice. Thus, we show, for the first time, a
      mammalian axonemal targeting sequence that localizes a sAC variant to cilia to
      regulate CBF. 

PMID- 24874275
TI  - In situ fabrication of a temperature- and ethanol-responsive smart membrane in a
      microchip.
AB  - Here we report a simple and versatile strategy for the in situ fabrication of
      nanogel-containing smart membranes in microchannels of microchips. The
      fabrication approach is demonstrated by the in situ formation of a chitosan
      membrane containing poly(N-isopropylacrylamide) (PNIPAM) nanogels in a
      microchannel of a microchip. The PNIPAM nanogels, that allow temperature- and
      ethanol-responsive swelling-shrinking volume transitions, serve as smart
      nanovalves for controlling the diffusional permeability of solutes across the
      membrane. Such self-regulation of the membrane permeability is investigated by
      using fluorescein isothiocyanate (FITC) as a tracer molecule. This approach
      provides a promising strategy for the in situ fabrication of versatile nanogel
      containing smart membranes within microchips via simply changing the functional
      nanogels for developing micro-scale detectors, sensors, separators and controlled
      release systems. 

PMID- 24874274
TI  - Dupuytren's disease involving Guyon's canal.
AB  - Ectopic localization of Dupuytren's contracture is extremely rare. To the best of
      our knowledge, there have been only six cases reported in the literature. The
      authors present a case with Dupuytren's contracture involving Guyon's canal where
      the patient had limited wrist range of motion and ulnar neuropathy.

PMID- 24874277
TI  - Local structure and La L1 and L3-edge XANES spectra of lanthanum complex oxides.
AB  - La L1 and L3-edge X-ray absorption near-edge structure (XANES) of various La
      oxides were classified according to the local configuration of La. We found a
      correlation between both of the areas of the pre-edge peaks of the La L1-edge
      XANES spectra and the full width at half-maximum of white line of La L3-edge
      XANES spectra and the local configuration of La. Theoretical calculation of the
      XANES spectra and local density of states reveals the difference of La L1 and L3
      edge XANES spectra of various La compounds is related to the p-d hybridization of
      the unoccupied band and broadening of the d band of La induced by the difference
      of local configuration. In addition, simplified bond angle analysis parameters
      defined by the angles of the La atom and the two adjacent oxygen atoms are
      correlated to the pre-edge peak intensity of the La L1-edge XANES spectra. These
      results indicate that quantitative analysis of La L1 and L3-edge XANES spectra
      could be an indicator of the local structure of La materials. 

PMID- 24874276
TI  - GPER mediates enhanced cell viability and motility via non-genomic signaling
      induced by 17beta-estradiol in triple-negative breast cancer cells.
AB  - Triple-negative breast cancer (TNBC) is an aggressive breast cancer with a
      generally poor prognosis. Due to lack of specific targets for its treatment, an
      efficient therapy is needed. G protein-coupled estrogen receptor (GPER), a novel
      estrogen receptor, has been reported to be expressed in TNBC tissues. In this
      study, we investigated the effects of blocking non-genomic signaling mediated by
      the estrogen/GPER pathway on cell viability and motility in the TNBC cells. GPER
      was strongly expressed in the TNBC cell lines MDA-MB-468 and MDA-MB-436, and the
      estrogen-mediated non-genomic ERK signaling activated by GPER was involved in
      cell viability and motility of TNBC cells. Treatment with 17beta-estradiol (E2),
      the GPER-specific agonist G-1 and tamoxifen (TAM) led to rapid activation of p
      ERK1/2, but not p-Akt. Moreover, estrogen/GPER/ERK signaling was involved in
      increasing cell growth, survival, and migration/invasion by upregulating
      expression of cyclinA, cyclinD1, Bcl-2, and c-fos associated with the cell cycle,
      proliferation, and apoptosis. Immunohistochemical analysis of TNBC specimens
      showed a significantly different staining of p-ERK1/2 between GPER-positive
      tissues (58/66, 87.9%) and GPER-negative tissues (13/30, 43.3%). The positivity
      of GPER and p-ERK1/2 displayed a strong association with large tumor size and
      poor clinical stage, indicating that GPER/ERK signaling might also contribute to
      tumor progression in TNBC patients which corresponded with in vitro experimental
      data. Our findings suggest that inhibition of estrogen/GPER/ERK signaling
      represents a novel targeted therapy in TNBC. 

PMID- 24874279
TI  - Mechanism of antiplatelet action of hypolipidemic, antidiabetic and
      antihypertensive drugs by PPAR activation: PPAR agonists: new antiplatelet
      agents.
AB  - Given the prevalence of cardiovascular disease in patients with cardiovascular
      risk factors (i.e., hypertension, diabetes, smoking and obesity) and that
      platelet activation plays an important pathogenic role in cardiovascular
      diseases, it is very important to identify the drugs that have multiple targets.
      In this sense, the present article describes the mechanism of antiplatelet action
      of hypolipidemic (statins and fibrates), antidiabetic (thiazolidinediones) and
      antihypertensive (nifedipine) drugs via peroxisome proliferator-activated
      receptor (PPAR) activation. The mechanism of antiplatelet action of the drugs is
      by direct activation of PPARs with the inhibition of cyclooxygenase-1, protein
      kinase C-alpha, calcium mobilization, thromboxane A2, sCD40L, platelet
      microparticles and cAMP-phosphodiesterase, and the stimulation of proteins kinase
      G and A. Thus, these observations highlight PPARs as a novel therapeutic target
      for the treatment and prevention of cardiovascular diseases. 

PMID- 24874278
TI  - Emerging topic: flow-related epigenetic regulation of endothelial phenotype
      through DNA methylation.
AB  - Atherosclerosis is a multi-focal disease; it is associated with arterial
      curvatures, asymmetries and branches/bifurcations where non-uniform arterial
      geometry generates patterns of blood flow that are considerably more complex than
      elsewhere, and are collectively referred to as disturbed flow. Such regions are
      predisposed to atherosclerosis and are the sites of 'athero-susceptible'
      endothelial cells that express regionally different cell phenotypes than
      endothelium in nearby athero-protected locations. The regulatory hierarchy of
      endothelial function includes control at the epigenetic level. MicroRNAs and
      histone modifications are established epigenetic regulators that respond to
      disturbed flow. However, very recent reports have linked transcriptional
      regulation by DNA methylation to endothelial gene expression in disturbed flow in
      vivo and in vitro. We outline these in the context of site-specific
      atherosusceptibility mediated by local hemodynamics. 

PMID- 24874282
TI  - Age-related changes in visual lobe shape characteristics and their relationship
      to visual search performance.
AB  - Visual lobe shape plays an important role in visual search performance, but
      little is known about the age-related changes in visual lobe shape. The age
      related changes in visual lobe shape characteristics and their relationships to
      visual search performance were investigated in this study. A total of 96
      participants aged 15-64 years participated in this study. Their visual lobes were
      mapped on a uniform 2-D test field composed of 24 regularly spaced meridians
      passing through the centre of the visual field, and their search performances
      were also measured. The results showed that in general, age significantly
      affected visual lobe size, visual lobe shape and search time. As age increased,
      the visual lobe size decreased; in addition, the roundness, boundary smoothness,
      symmetry and regularity of the visual lobe deteriorated, and the search time
      increased. Moreover, significant correlations between visual lobe shape, search
      time and age were found. Regression analyses indicated that age was important in
      determining visual lobe shape and search time, suggesting that age differences
      should be considered when predicting search time and when designing tasks and
      products that involve visual search in our daily lives and work. PRACTITIONER
      SUMMARY: Age-related changes in visual lobe shape characteristics and their
      relationships to visual search performance were investigated in this study. The
      results help to explain how tasks and products involving visual search in our
      daily lives and work should be designed for target audiences of different ages.

PMID- 24874280
TI  - Joint variant and de novo mutation identification on pedigrees from high
      throughput sequencing data.
AB  - The analysis of whole-genome or exome sequencing data from trios and pedigrees
      has been successfully applied to the identification of disease-causing mutations.
      However, most methods used to identify and genotype genetic variants from next
      generation sequencing data ignore the relationships between samples, resulting in
      significant Mendelian errors, false positives and negatives. Here we present a
      Bayesian network framework that jointly analyzes data from all members of a
      pedigree simultaneously using Mendelian segregation priors, yet providing the
      ability to detect de novo mutations in offspring, and is scalable to large
      pedigrees. We evaluated our method by simulations and analysis of whole-genome
      sequencing (WGS) data from a 17-individual, 3-generation CEPH pedigree sequenced
      to 50* average depth. Compared with singleton calling, our family caller produced
      more high-quality variants and eliminated spurious calls as judged by common
      quality metrics such as Ti/Tv, Het/Hom ratios, and dbSNP/SNP array data
      concordance, and by comparing to ground truth variant sets available for this
      sample. We identify all previously validated de novo mutations in NA12878,
      concurrent with a 7* precision improvement. Our results show that our method is
      scalable to large genomics and human disease studies.

PMID- 24874283
TI  - Use of antacids, alginates and proton pump inhibitors: a survey of the general
      Danish population using an internet panel.
AB  - OBJECTIVE: Both over-the-counter medicine, such as antacids or alginates, and
      proton pump inhibitors (PPI) are used for treating acid-related disorders. We
      sought to describe what characterizes users of these different medicines,
      including long-term PPI users within the general population. METHOD: A cross
      sectional survey was conducted in an internet panel representative of the Danish
      adult population in 2012. Data queried included antacid/alginate and PPI use,
      reason for therapy, co-medication, and presence of upper gastrointestinal
      symptoms. Long-term PPI use was defined as using PPI >=1/3 of the last year (~120
      days). Risk of long-term PPI use was estimated by logistic regression. RESULTS: A
      total of 18,223 people received the questionnaire, of which 52% (9390) responded.
      Antacid/alginate use was reported by 23%; 16% reported use of only
      antacid/alginate. PPI use was reported by 13.6%; 6.2% were defined as long-term
      PPI users. Antacid/alginate users were younger, used less co-medication, had most
      often started on therapy because of reflux symptoms, and had less often ongoing
      symptoms. Risk of long-term PPI use appeared to be increased in male gender, by
      renewing PPI prescription by phone/e-mail, using co-medication, and having
      started on PPI for several reasons. Combination of antacid/alginate and PPI was
      reported by approximately 50% of those on therapy with weekly or daily symptoms.
      CONCLUSION: 23% of Danish adults were using antacids or alginates and 14% were
      using PPI, of which one-half were on long-term therapy. Prescription renewal by
      phone or e-mail and use of other prescription medication were associated with
      long-term PPI use, indicating a behavioral pattern, in which unnecessary PPI
      therapy may be maintained.

PMID- 24874284
TI  - Prognostic value of isolated tumor cells and micrometastases of lymph nodes in
      early-stage breast cancer: a French sentinel node multicenter cohort study.
AB  - To define the prognostic value of isolated tumor cells (ITC), micrometastases
      (pN1mi) and macrometastases in early stage breast cancer (ESBC). We conducted a
      retrospective multicenter cohort study at 13 French sites. All the eligible
      patients who underwent SLNB from January 1999 to December 2008 were identified,
      and appropriate data were extracted from medical records and analyzed. Among 8001
      patients, including 70% node-negative (n = 5588), 4% ITC (n = 305), 10% pN1mi (n
      = 794) and 16% macrometastases (n = 1314) with a median follow-up of 61.3 months,
      overall survival (OS) and recurrence-free survival (RFS) rates at 84 months were
      not statistically different in ITC or pN1mi compared to tumor-free nodes.
      Axillary recurrence (AR) was significantly more frequent in ITC (1.7%) and pN1mi
      (1.5%) compared to negative nodes (0.6%). Survival and AR rates of single
      macrometastases were not different from those of ITC or pN1mi. In case of 2
      macrometastases or more, survival rates decreased and recurrence rates increased
      significantly. Micrometastases and ITC do not have a negative prognostic value.
      Single macrometastases might have an intermediate prognostic value while 2
      macrometastases or more are associated with poorer prognosis.

PMID- 24874285
TI  - Pilot randomised study of early intervention based on tumour markers in the
      follow-up of patients with primary breast cancer.
AB  - BACKGROUND: This pilot study aimed to test the possibility of therapeutic benefit
      imparted by early intervention based on sequential tumour marker (TM)
      measurements during follow-up of primary breast cancer (PBC) patients. METHODS:
      Patients with oestrogen receptor positive PBC with no clinical and/or
      radiological evidence of metastases were recruited and followed-up 3-monthly with
      clinical assessment and TM (CA15.3 and CEA) measurements. The clinical team was
      blinded to the TM results. Asymptomatic patients who developed raised TMs (based
      on pre-defined cut-offs) were randomised to either 'treatment change' (either
      start or change of adjuvant endocrine agent to another agent) or 'no change'
      (control). Patients who developed symptomatic metastases came off the study. The
      primary and secondary endpoints were intervals from randomisation to symptomatic
      metastases and to last follow-up/death respectively. RESULTS: Eighty-five
      patients (median age = 54 years (30-72)) were recruited with a median follow-up
      of 81 months (1-124). Sixteen patients were randomised as described. There was no
      significant difference (treatment change versus no change) with regards to
      interval from randomisation to symptomatic metastases - 23 (2-62) and 22 (1-63)
      months respectively (p = 0.9), as well as interval from randomisation to last
      follow-up/death - 36 (7-63) and 37 (10-63) months respectively (p = 0.9).
      CONCLUSIONS: Despite long follow-up (up to 10+ years), this small study has thus
      far shown no significant difference in outcome. However, we have confirmed the
      feasibility of this study design but a larger study will be required to show if
      there is a benefit to this approach.

PMID- 24874286
TI  - Combination of gefitinib and DNA methylation inhibitor decitabine exerts
      synergistic anti-cancer activity in colon cancer cells.
AB  - Despite recent advances in the treatment of human colon cancer, the chemotherapy
      efficacy against colon cancer is still unsatisfactory. In the present study,
      effects of concomitant inhibition of the epidermal growth factor receptor (EGFR)
      and DNA methyltransferase were examined in human colon cancer cells. We
      demonstrated that decitabine (a DNA methyltransferase inhibitor) synergized with
      gefitinib (an EGFR inhibitor) to reduce cell viability and colony formation in
      SW1116 and LOVO cells. However, the combination of the two compounds displayed
      minimal toxicity to NCM460 cells, a normal human colon mucosal epithelial cell
      line. The combination was also more effective at inhibiting the AKT/mTOR/S6
      kinase pathway. In addition, the combination of decitabine with gefitinib
      markedly inhibited colon cancer cell migration. Furthermore, gefitinib
      synergistically enhanced decitabine-induced cytotoxicity was primarily due to
      apoptosis as shown by Annexin V labeling that was attenuated by z-VAD-fmk, a pan
      caspase inhibitor. Concomitantly, cell apoptosis resulting from the co-treatment
      of gefitinib and decitabine was accompanied by induction of BAX, cleaved caspase
      3 and cleaved PARP, along with reduction of Bcl-2 compared to treatment with
      either drug alone. Interestingly, combined treatment with these two drugs
      increased the expression of XIAP-associated factor 1 (XAF1) which play an
      important role in cell apoptosis. Moreover, small interfering RNA (siRNA)
      depletion of XAF1 significantly attenuated colon cancer cells apoptosis induced
      by the combination of the two drugs. Our findings suggested that gefitinib in
      combination with decitabine exerted enhanced cell apoptosis in colon cancer cells
      were involved in mitochondrial-mediated pathway and induction of XAF1 expression.
      In conclusion, based on the observations from our study, we suggested that the
      combined administration of these two drugs might be considered as a novel
      therapeutic regimen for treating colon cancer. 

PMID- 24874290
TI  - The granulocyte macrophage-colony stimulating factor surface modified MB49
      bladder cancer stem cells vaccine against metastatic bladder cancer.
AB  - The MB49 bladder cancer cell vaccine was effective against bladder cancer in the
      mice model in previous studies. However, part of the tumors regrew as the vaccine
      could not eliminate the cancer stem cells (CSCs). MB49 bladder cancer stem cells
      (MCSCs) were isolated by a combination of the limited dilution method and the
      serum free culture medium method. MCSCs possessed higher expression of CD133,
      CD44, OCT4, NANOG, and ABCG2, the ability of differentiation, higher
      proliferative abilities, lower susceptibility to chemotherapy, greater migration
      in vitro, and stronger tumorigenic abilities in vivo. Then streptavidin-mouse
      granulocyte macrophage-colony stimulating factor (SA-mGM-CSF) MCSCs vaccine was
      prepared. SA-mGM-CSF MCSCs vaccine extended the survival of the mice and
      inhibited the growth of tumor in protective, therapeutic, memorial and specific
      immune response experiments. The level of immunoglobulin G and the ratio of
      dendritic cells and CD4(+) and CD8(+) T cells were highest in the experimental
      group when compared to those in other four control groups, as well as for the
      cytotoxicity assay. We demonstrated that SA-mGM-CSF MCSCs vaccine induces an
      antitumor immune response to metastatic bladder cancer. 

PMID- 24874291
TI  - Identification of histone H3 clipping activity in human embryonic stem cells.
AB  - Posttranslational histone modifications are essential features in epigenetic
      regulatory networks. One of these modifications has remained largely
      understudied: regulated histone proteolysis. In analogy to the histone H3
      clipping during early mouse embryonic stem cell differentiation, we report for
      the first time that also in human embryonic stem cells this phenomenon takes
      place in the two different analyzed cell lines. Employing complementary
      techniques, different cleavage sites could be identified, namely A21, R26 and
      residue 31. The enzyme responsible for this cleavage is found to be a serine
      protease. The formation of cleaved H3 follows a considerably variable pattern,
      depending on the timeframe, culture conditions and culture media applied.
      Contrary to earlier findings on H3 clipping, our results disconnect the link
      between declining Oct4 expression and H3 cleavage. 

PMID- 24874292
TI  - High-efficiency organic light-emitting diodes with fluorescent emitters.
AB  - Fluorescence-based organic light-emitting diodes have continued to attract
      interest because of their long operational lifetimes, high colour purity of
      electroluminescence and potential to be manufactured at low cost in next
      generation full-colour display and lighting applications. In fluorescent
      molecules, however, the exciton production efficiency is limited to 25% due to
      the deactivation of triplet excitons. Here we report fluorescence-based organic
      light-emitting diodes that realize external quantum efficiencies as high as 13.4
      18% for blue, green, yellow and red emission, indicating that the exciton
      production efficiency reached nearly 100%. The high performance is enabled by
      utilization of thermally activated delayed fluorescence molecules as assistant
      dopants that permit efficient transfer of all electrically generated singlet and
      triplet excitons from the assistant dopants to the fluorescent emitters. Organic
      light-emitting diodes employing this exciton harvesting process provide freedom
      for the selection of emitters from a wide variety of conventional fluorescent
      molecules. 

PMID- 24874288
TI  - Non-viral nanocarriers for siRNA delivery in breast cancer.
AB  - Breast cancer is the most frequently diagnosed malignancy in American women.
      While significant progress has been made in the development of modern diagnostic
      tools and surgical treatments, only marginal improvements have been achieved with
      relapsed metastatic breast cancer. Small interfering RNAs (siRNAs) mediate gene
      silencing of a target protein by disrupting messenger RNAs in an efficient and
      sequence-specific manner. One application of this technology is the knockdown of
      genes responsible for tumorigenesis, including those driving oncogenesis,
      survival, proliferation and death of cells, angiogenesis, invasion and
      metastasis, and resistance to treatment. Non-viral nanocarriers have attracted
      attention based on their potential for targeted delivery of siRNA and efficient
      gene silencing without toxicity. Here, we review promising, non-viral delivery
      strategies employing liposomes, nanoparticles and inorganic materials in breast
      cancer. 

PMID- 24874294
TI  - Extortion subdues human players but is finally punished in the prisoner's
      dilemma.
AB  - Extortion is the practice of obtaining advantages through explicit forces and
      threats. Recently, it was demonstrated that even the repeated prisoner's dilemma,
      one of the key models to explain mutual cooperation, allows for implicit forms of
      extortion. According to the theory, extortioners demand and receive an excessive
      share of any surplus, which allows them to outperform any adapting co-player. To
      explore the performance of such strategies against humans, we have designed an
      economic experiment in which participants were matched either with an extortioner
      or with a generous co-player. Although extortioners succeeded against each of
      their human opponents, extortion resulted in lower payoffs than generosity. Human
      subjects showed a strong concern for fairness: they punished extortion by
      refusing to fully cooperate, thereby reducing their own, and even more so, the
      extortioner's gains. Thus, the prospects of extorting others in social
      relationships seem limited; in the long run, generosity is more profitable. 

PMID- 24874293
TI  - Decreased prefrontal cortical dopamine transmission in alcoholism.
AB  - OBJECTIVE: Basic studies have demonstrated that optimal levels of prefrontal
      cortical dopamine are critical to various executive functions such as working
      memory, attention, inhibitory control, and risk/reward decisions, all of which
      are impaired in addictive disorders such as alcoholism. Based on this and imaging
      studies of alcoholism that have demonstrated less dopamine in the striatum, the
      authors hypothesized decreased dopamine transmission in the prefrontal cortex in
      persons with alcohol dependence. METHOD: To test this hypothesis, amphetamine and
      [11C]FLB 457 positron emission tomography were used to measure cortical dopamine
      transmission in 21 recently abstinent persons with alcohol dependence and 21
      matched healthy comparison subjects. [11C]FLB 457 binding potential, specific
      compared to nondisplaceable uptake (BPND), was measured in subjects with kinetic
      analysis using the arterial input function both before and after 0.5 mg kg-1 of d
      amphetamine. RESULTS: Amphetamine-induced displacement of [11C]FLB 457 binding
      potential (DeltaBPND) was significantly smaller in the cortical regions in the
      alcohol-dependent group compared with the healthy comparison group. Cortical
      regions that demonstrated lower dopamine transmission in the alcohol-dependent
      group included the dorsolateral prefrontal cortex, medial prefrontal cortex,
      orbital frontal cortex, temporal cortex, and medial temporal lobe. CONCLUSIONS:
      The results of this study, for the first time, unambiguously demonstrate
      decreased dopamine transmission in the cortex in alcoholism. Further research is
      necessary to understand the clinical relevance of decreased cortical dopamine as
      to whether it is related to impaired executive function, relapse, and outcome in
      alcoholism.

PMID- 24874289
TI  - State-of-the-art in design rules for drug delivery platforms: lessons learned
      from FDA-approved nanomedicines.
AB  - The ability to efficiently deliver a drug to a tumor site is dependent on a wide
      range of physiologically imposed design constraints. Nanotechnology provides the
      possibility of creating delivery vehicles where these design constraints can be
      decoupled, allowing new approaches for reducing the unwanted side effects of
      systemic delivery, increasing targeting efficiency and efficacy. Here we review
      the design strategies of the two FDA-approved antibody-drug conjugates
      (Brentuximab vedotin and Trastuzumab emtansine) and the four FDA-approved
      nanoparticle-based drug delivery platforms (Doxil, DaunoXome, Marqibo, and
      Abraxane) in the context of the challenges associated with systemic targeted
      delivery of a drug to a solid tumor. The lessons learned from these nanomedicines
      provide an important insight into the key challenges associated with the
      development of new platforms for systemic delivery of anti-cancer drugs. 

PMID- 24874296
TI  - Switchable spin-current source controlled by magnetic domain walls.
AB  - Using nonlocal spin injection, spin-orbit coupling, or spincaloritronic effects,
      the manipulation of pure spin currents in nanostructures underlies the
      development of new spintronic devices. Here, we demonstrate the possibility to
      create switchable pure spin current sources, controlled by magnetic domain walls.
      When the domain wall is located at a given point of the magnetic circuit, a pure
      spin current is injected into a nonmagnetic wire. Using the reciprocal
      measurement configuration, we demonstrate that the proposed device can also be
      used as a pure spin current detector. Thanks to its simple geometry, this device
      can be easily implemented in spintronics applications; in particular, a single
      current source can be used both to induce the domain wall motion and to generate
      the spin signal. 

PMID- 24874295
TI  - Pentoxifylline alleviates cardiac ischemia and dysfunction following experimental
      angina in insulin resistance.
AB  - We have previously shown that pentoxifylline (PTX) protects from vascular
      complications associated with insulin resistance (IR). Here, we investigated the
      protective effect of PTX against cardiac ischemia and dysfunction following
      experimental angina in IR. IR, along with its accompanying cardiac dysfunction,
      was induced in rats by a high-fructose (10% in drinking water) high-fat diet for
      12 weeks. PTX was administered daily (30 mg?kg(-1)) during the last 4 weeks of
      the study. Experimental angina was induced by isoproterenol (10 ug?kg(-1))
      administered by intravenous injection. Both before (baseline) and after the
      experimental angina, cardiac contractility was assessed by continuous recording
      in anesthetized rats via a microtip catheter inserted in the left ventricle, and
      cardiac conductivity was determined by a surface electrocardiograph. Serum
      glucose, insulin, tumor necrosis factor-alpha (TNFalpha), and adiponectin levels
      and lipid profile were also determined. Feeding the rats a high-fructose high-fat
      diet produced IR, as evidenced by significant hyperinsulinemia and hyperglycemia,
      and PTX administration did not affect this IR. When subjected to experimental
      angina, IR hearts were less resistant to the ischemia following induction of
      angina (reflected by the large ST height depression) compared with controls, and
      PTX completely prevented the excessive ST height depression in IR animals. In
      addition, left ventricular pressure development was largely attenuated during and
      after induction of angina in IR animals compared with controls. PTX
      administration prevented the excessive attenuation in ventricular pressure
      development in IR animals. IR was associated with elevated levels of the
      inflammatory cytokine TNFalpha, whereas PTX treatment elevated the serum level of
      the anti-inflammatory cytokine adiponectin. PTX alleviates cardiac ischemia and
      dysfunction following experimental angina in IR directly through inhibition of
      the low-grade inflammation that accompanies IR.

PMID- 24874297
TI  - Can the effect of transepithelial corneal collagen cross-linking be improved by
      increasing the duration of topical riboflavin application? An in vivo confocal
      microscopy study.
AB  - OBJECTIVE: To evaluate the effect of transepithelial corneal collagen cross
      linking (CXL) with prolonged riboflavin application by in vivo confocal
      microscopy and to compare this effect with that of standard CXL with complete
      epithelial debridement. METHODS: In eyes with progressive keratoconus, CXL
      procedure was performed with standard technique and transepithelial technique
      after prolonged riboflavin drop application for 2 hr. Patients were evaluated
      with in vivo confocal microscopic examination preoperatively and at postoperative
      months 1 and 6. RESULTS: The depth of CXL effect was similar in both groups
      (i.e., 380.86 +/- 103.23 MUm in standard CXL group and 342.2 +/- 68.6 MUm in
      transepithelial CXL group) (P=0.4). The endothelial cell counts and morphological
      parameters (i.e., pleomorphism and polymegathism) were not significantly affected
      in both groups (P>0.05 for all). In the standard CXL group, in vivo confocal
      microscopy revealed anterior stromal acellular hyperreflective honeycomb edema
      with posteriorly gradually decreasing reflectivity and increasing number of
      keratocytes and some sheets of longitudinally aligned filamentary deposits. The
      keratocytes were seen to repopulate in the posterior-to-anterior direction. In
      transepithelial CXL group, although the depth of CXL effect was similar, less
      pronounced keratocyte damage, extracellular matrix hyperreflectivity, and sheets
      of filamentary deposits at the posterior stroma was observed. CONCLUSIONS:
      Transepithelial CXL with prolonged peroperative riboflavin application can
      achieve similar depth of effect in the stroma with less pronounced confocal
      microscopic changes as compared with the standard CXL with complete epithelial
      debridement.

PMID- 24874298
TI  - Effect of religious fasting on tear osmolarity and ocular surface.
AB  - OBJECTIVE: To evaluate the effects of religious fasting on tear secretion, tear
      osmolarity, corneal topography, and ocular aberrations. METHODS: This prospective
      controlled study comprised 29 eyes of 29 healthy men. Before ophthalmologic
      examination, all subjects underwent corneal topography by a placido disc corneal
      topography and aberrometry device (OPD Scan II). Tear osmolarity was measured
      using OcuSense TearLab osmometer. Ocular surface disease index (OSDI) scores,
      tear break-up time (BUT), Schirmer I test, and lissamine green staining were
      evaluated. The measurements taken before and during Ramadan at the same hours
      between 4.00 and 5.00 PM were compared using paired sample t test, and a P value
      less than 0.05 was accepted as statistically significant. RESULTS: The mean age
      of the study group was 27.8 +/- 5.9 years (range, 20-47 years). The mean tear
      osmolarity values were measured as 285.6 +/- 8.2 mOsm/L and 293.3 +/- 16.0
      mOsm/L, whereas the mean Schirmer I values were 14.8 +/- 6.0 mm and 10.6 +/- 5.3
      mm in nonfasting and fasting periods, respectively. Tear osmolarity, OSDI, and
      Oxford grading scores significantly increased (P=0.02, P=0.002, P=0.003,
      respectively), whereas Schirmer I values and intraocular pressure decreased
      (both, P<0.001) during the fasting period compared with the nonfasting period.
      There were no significant differences in tear BUT, keratometry values, and
      corneal aberration measurements between nonfasting and fasting periods (P>0.05,
      for all). CONCLUSION: Fasting significantly decreases tear production and
      increases tear osmolarity; however, it does not deteriorate corneal topographic
      parameters and ocular aberrations in healthy subjects.

PMID- 24874301
TI  - Thermophysical investigation of Gafchromic EBT2 films using photoacoustic
      spectroscopy.
AB  - The thermophysical properties of EBT2 films exposed to different doses of x-ray
      were investigated. The doses ranged from 2 to 818 cGy. The films were irradiated
      by a Varian linear accelerator using a 6 MV photon beam. The thermal conductivity
      (k) was obtained by measuring the thermal diffusivity (alpha) and thermal
      effusivity (e) using the photoacoustic (PA) technique. The alpha, e, and k values
      clearly indicated their dependence on the dose from 0 to 818 cGy. The results
      demonstrate that the PA technique can detect variations in the thermal
      diffusivity at doses as low as approximately 3 cGy. The thermal conductivity for
      the film exposed to 818 cGy of radiation increased by a factor of approximately
      3.70 compared to the non-exposed film. The PA spectroscopic technique displayed
      good reproducibility, with a relative standard deviation of less than 5%. 

PMID- 24874300
TI  - Multiple stimuli-switchable bioelectrocatalysis under physiological conditions
      based on copolymer films with entrapped enzyme.
AB  - In the present work, N,N-diethylacrylamide (DEA) and methyl acrylic acid (MAA)
      monomers were copolymerized into P(DEA-co-MAA) thin films on the electrode
      surface with a simple one-step polymerization method at ambient temperature and
      pressure, and the enzyme glucose oxidase (GOD) was entrapped in the films,
      designed as P(DEA-co-MAA)-GOD. The cyclic voltammetric (CV) response of ferrocene
      dicarboxylic acid (Fc(COOH)2) at the film electrodes was very sensitive to
      environmental stimuli, such as temperature, pH, the identity and concentration of
      anions, and the concentration of CO2 in solution. This multiresponsive CV
      behavior of the system could be further employed to switch the electrochemical
      oxidation of glucose catalyzed by GOD entrapped in the films with Fc(COOH)2 as
      the mediator in solution, demonstrating the amplification effect. The SEM and
      stereomicroscopy results showed that the multisensitive behaviors of the system
      were attributed to the structure change of the copolymer films with the stimuli.
      Specifically, the synergistic effect of temperature and pH was observed, and the
      hydrogen bonding between PDEA and PMAA components in the copolymer played a key
      role for this. The present system could be performed under physiological
      conditions at 37  degrees C and pH 7.4, which may offer numerous possibilities
      not only to design new multiswitchable biosensors based on bioelectrocatalysis
      but also to establish foundations for controlled drug delivery and other medical
      applications. 

PMID- 24874299
TI  - Current breast cancer proliferative markers correlate variably based on decoupled
      duration of cell cycle phases.
AB  - Mitotic count, PhH3, and MIB-1 are used as measures of the proportion of
      proliferating malignant cells in surgical pathology. They highlight different
      stages of the cell cycle, but little is known about how this affects their
      counts. This study assesses the strength of their correlations and attempts to
      determine the relationship between them. Proliferation counts for forty-nine
      consecutive cases of invasive breast carcinomas were analyzed, with the same
      tumor area on each stain counted using digital image analysis. The integrated
      optical density (IOD) of nuclei was measured as an approximation of nuclear DNA
      content. PhH3 strongly correlated with mitotic count (r = 0.94). Weaker
      correlations were found between MIB-1 versus PhH3 (r = 0.79) and mitotic count (r
      = 0.83). Nuclear IOD showed stronger correlation with MIB-1 (r = 0.37) than to
      mitotic count (r = 0.23) and PhH3 (r = 0.34). With evidence from a literature
      review, it is suggested that the weaker correlations with MIB-1 are not explained
      by count imprecision or error, but relies on temporal decorrelation between cell
      cycle phases. Consequences on correlation between these proliferative markers are
      illustrated by mathematical models. 

PMID- 24874302
TI  - Association of CD209 and CD209L polymorphisms with tuberculosis infection in a
      Northeastern Brazilian population.
AB  - Tuberculosis (TB) caused by Mycobacterium tuberculosis, is major cause of
      morbidity and mortality worldwide. So far, many candidate genes have been
      investigated for their possible association with TB. Dendritic cell-specific
      intercellular adhesion molecule 3 (ICAM-3) grabbing non-integrin (DC-SIGN) and
      Liver/lymph node-specific intercellular adhesion molecule-grabbing non-integrin
      (L-SIGN), encoded by CD209 and CD209L genes respectively, are known for binding
      to M. tuberculosis on human dendritic cells and macrophages. We screened 4 single
      nucleotide polymorphisms (SNPs) in the promoter region of CD209, namely -939G>A
      (rs735240), -871A>G (rs735239), -336A>G (rs4804803) and -139G>A (rs2287886) and
      tandem repeat polymorphisms in exon 4 of CD209 and CD209L genes looking for
      association with TB in a Northeastern Brazilian population (295 subjects, 131 TB
      patients and 164 healthy controls). The -139G>A and -939G>A SNPs were associated
      with susceptibility to TB, and in particular with pulmonary and extra-pulmonary
      forms respectively. The -871A>G and -336A>G SNPs were associated, the first with
      protection to both pulmonary and extra-pulmonary TB, the latter only with the
      pulmonary form. An association between GGAG haplotype and protection to TB
      infection was also found. Also tandem repeat polymorphism in CD209L exon 4 was
      associated with TB infection. This study provides evidence of an association
      between CD209 and CD209L polymorphisms and TB development in a Brazilian
      population, suggesting that variations in these genes may influence the
      protection and susceptibility to infection caused by M. tuberculosis. 

PMID- 24874303
TI  - Binding of novel 9-O-N-aryl/arylalkyl amino carbonyl methyl berberine analogs to
      poly(U)-poly(A).poly(U) triplex and comparison to the duplex poly(A)-poly(U).
AB  - Interaction of the 9-O-N-aryl/arylalkyl amino carbonyl methyl substituted analogs
      of the anticancer isoquinoline alkaloid berberine with RNA triplex, poly(U)
      poly(A) . poly(U) has been studied in comparison to the duplex poly(A)-poly(U),
      using multiple biophysical techniques. Spectrophotometric and spectrofluorimetric
      studies established the non-cooperative binding mode of all the analogs with both
      the duplex and the triplex. However, berberine exhibited cooperative binding with
      poly(A)-poly(U) and non-cooperative binding with poly(U)-poly(A) . poly(U).
      Analog BER1 showed the highest affinity to both the duplex and the triplex
      followed by BER2 and BER3. The overall binding affinity varied as BER1 > BER2 >
      BER3 > BER. The magnitude of the quantum efficiency values (Q > 1) revealed that
      energy was transferred from the bases of the triplex and the duplex to the
      analogs. Comparative ferrocyanide quenching and viscosity studies unambiguously
      established a stronger intercalative geometry of the analogs to both the triplex
      and the duplex in comparison to berberine. Circular dichroism studies revealed
      that the alkaloids perturbed the conformation of both RNA helices. The binding of
      all the alkaloids was found to be exothermic from isothermal titration studies.
      Binding of the analogs was highly entropy driven while that of berberine was
      enthalpy dominated. The results presented here reveal strong and specific binding
      of these new berberine analogs to the RNA triplex and duplex and highlight the
      remarkable influence of the 9-substitution on the interaction profile.

PMID- 24874304
TI  - MMP-9 gene ablation mitigates hyperhomocystenemia-induced cognition and hearing
      dysfunction.
AB  - Hyperhomocysteinemia (HHcy) is associated with cognitive decline and hearing loss
      due to vascular dysfunction. Although we have shown that HHcy-induced increased
      expression of matrix metalloproteinase-9 (MMP-9) is associated with cochlear
      pathology in cystathionine-beta-synthase heterozygous (CBS(+/-)) mice, it is
      still unclear whether MMP-9 contributes to functional deficit in cognition and
      hearing. Therefore, we hypothesize that HHcy-induced MMP-9 activation causes
      vascular, cerebral and cochlear remodeling resulting in diminished cognition and
      hearing. Wildtype (WT), CBS(+/-), MMP-9(-/-) and CBS(+/-)/MMP-9(-/-) double knock
      out (DKO) mice were genotyped and used. Doppler flowmetry of internal carotid
      artery (ICA) was performed for peak systolic velocity [PSV], pulsatility index
      [PI] and resistive index [RI]. Cognitive functions were assessed by Novel Object
      Recognition Test (NORT) and for cochlear function Auditory brainstem response
      (ABR) was elicited. Peak systolic velocity, pulsatility and resistive indices of
      ICA were decreased in CBS(+/-) mice, indicating reduced perfusion. ABR threshold
      was increased and maximum ABR amplitude and NORT indices (recognition,
      discrimination) were decreased in CBS(+/-) mice compared to WT and MMP-9(-/-).
      All these parameters were attenuated in DKO mice suggesting a significant role of
      MMP-9 in HHcy-induced vascular, neural and cochlear pathophysiology. Regression
      analysis of PSV with ABR and cognitive parameters revealed significant
      correlation (0.44-0.58). For the first time, MMP-9 has been correlated directly
      to functional deficits of brain and cochlea, and found to have a significant
      role. Our data suggests a dual pathology of HHcy occurring due to a decrease in
      blood supply (vasculo-neural and vasculo-cochlear) and direct tissue remodeling. 

PMID- 24874305
TI  - The protective effect of rosmarinic acid on hyperthermia-induced C2C12 muscle
      cells damage.
AB  - High temperature will cause animal tissues or cells damage. Rosmarinic acid (RA)
      is a good antioxidant and health care product, but the roles of RA in muscle
      cells damage and the mechanisms which caused by high temperature is still
      unknown. In this study, the roles of RA on hyperthermia-induced apoptosis and
      damage of C2C12 muscle cells were investigated. C2C12 cells were cultured in
      medium with different concentration (0, 25, 50, 100 uM) RA and treated in 42 
      degrees C high temperature to induce cellular apoptosis and damage. Then, these
      cells were analyzed effect of different dose of RA on cells apoptosis and damage.
      The results indicated that RA has protective effect on heat-stress induced
      cellular damage, and the cells have the higher cell viability at the dose of 50
      uM RA by MTT assay. Hochest33342/PI double staining showed that the cellular
      apoptosis of C2C12 cells were decreased in the presence of selected 50 uM RA.
      Malondialdehyde formation and reactive oxygen species levels were also decreased
      significantly, but cellular superoxide dismutase activity was increased
      significantly in the presence of RA even in the condition of 42  degrees C.
      Meanwhile, Caspase-3 mRNA expression, Caspase-3 activity, and Bax/Bcl-2 ratio
      were reduced significantly, but the mRNA expression of Hsp72 was increased
      significantly in those hyperthermia-induced C2C12 cells in the presence of 50 uM
      RA. Taken together, the results at least discovered that RA has protective
      effects on hyperthermia-induced cellular apoptosis and damage of muscle cells by
      change the expression of stress-genes and increasing intracellular antioxidant
      capability.

PMID- 24874306
TI  - [Urinary calculi and infection].
AB  - Infection urinary stones resulting from urease-producing bacteria are composed by
      struvite and/or carbonate apatite. Bacterial urease splits urea and promotes the
      formation of ammonia and carbon dioxide leading to urine alkalinization and
      formation of phosphate salts. Proteus species are urease-producers, whereas a
      limited number of strains of other Gram negative and positive species may produce
      urease. Ureaplasma urealyticum and Corynebacterium urealyticum are urease
      producers that are not isolated by conventional urine cultures, but require
      specific tests for identification. Primary treatment requires surgical removal of
      stones as complete as possible. Extracorporeal and endoscopic treatments are
      usually preferred, while open surgery is actually limited to few selected cases.
      Residual stones or fragments should be treated by chemolysis via ureteral
      catheter or nephrostomy or administration of citrate salts in order to achieve a
      stone-free renal unit. Postoperatively, recurrent urinary tract infection should
      be treated with appropriate antibiotic treatment although long-term antibiotic
      prophylaxis can cause resistance. Urinary acidification has been proposed for the
      prophylaxis of infection stones, but long-term acidification is difficult to
      achieve in urine infected by urease-producing bacteria. Urease inhibitors lead to
      prevention and/or dissolution of stones and encrustations in patients with
      infection by urea-splitting bacteria, but their use is limited by their toxicity.
      The administration of citrate salts involves an increase of the value of
      nucleation pH (pHn), that is the pH value at which calcium and magnesium
      phosphate crystallization occurs, in a greater way than the corresponding
      increase in the urinary pH due to its alkalinizing effect and resulting in a
      reduction of the risk of struvite crystallization. In conclusion prevention of
      the recurrence of infection stones can be achieved by an integrated approach
      tailored on the single patient. Complete clearance of the stone must be achieved
      by primary surgical procedure and residual fragments should be extensively
      treated. In the case of persistent infection, conservative measures, such as
      acidification and urease inhibitors or citrate administration, should be adopted
      to minimize its effect on urinary saturation with respect to struvite. 

PMID- 24874307
TI  - Urinary diversion: long-term functional aspects.
AB  - Functional aspects and quality of life (QOL) of patients with a urinary diversion
      (UD) represent important issues in Urology. Any form of UD has its specific
      problems. In experienced hands and with regular long-term follow-up, serious
      complications can be avoided and excellent long-term results can be achieved.
      Thus, the selection of an appropriate UD is critical to patient's long-term
      satisfaction. Patients must be fully counseled in all types of UD and should have
      ready access to all options. There are 3 kinds of factors to be considered in the
      selection of UD: patient, physician, and general factors. In the pre-operative
      counseling, it is mandatory to explain all factors that over time may contribute
      to affect the patient's urinary tract function and QOL, mainly linked to long
      term complications of UD. One of the most important requirements for any bladder
      substitution is that it should not jeopardize the renal function. There are many
      urological and non-urological potential reasons for deterioration in renal
      function following UD. Continence results after neobladder (NB) are difficult to
      compare between series published in the literature because of a lack of consensus
      of definitions, varied follow-up periods, and different mechanisms of data
      collection. In up to 22% of patients with NB, significant residual urine volumes
      were observed. The overall patients' QOL reported in most articles was good,
      irrespective of the type of UD. QOL of patients with a well functioning NB seems
      to be significantly better than other forms of diversion. Well-designed
      randomized prospective trials are warranted to render definitive conclusions. 

PMID- 24874308
TI  - Expression of matrix metalloproteinases is positively related to the severity of
      disc degeneration and growing age in the East Asian lumbar disc herniation
      patients.
AB  - Matrix metalloproteinases (MMPs) have been known to play a pivotal role in the
      age- and/or disease-related degradation of intervertebral discs. We aimed to
      explore as to whether the expression of these enzymes is correlated to disc
      degeneration caused by increasing age and severity of herniation in the East
      Asian population. Thus, we studied the expressions of MMP-1 (collagenase), MMP-2
      (gelatinase) and MMP-14 (membrane-type protease) in 65 patients diagnosed with
      lumbar disc herniation. The patients were divided into 3 groups according to
      their age, and the severity of herniation was graded on the basis of magnetic
      resonance imaging (MRI). Immunohistochemistry analysis was conducted to determine
      the expression of different MMPs in the post-surgery disc specimens. The results
      showed that expressions of these three enzymes were directly and positively
      related to the degree of disc degradation. Whereas, the MMP-1 expression was
      found to be elevated with the increasing age, the MMP-2 and MMP-14 remained
      unchanged in groups of different ages. A direct correlation between the
      expressions of MMP-2 and MMP-14 suggested a role of MMP-14 in the modulation of
      MMP-2 expression. 

PMID- 24874309
TI  - [Negative mental disorders in epilepsy].
AB  - Objective. To search for clinical features of negative mental disorders in
      epilepsy. Material and methods. We studied 78 patients, aged from 18 to 40
      years,, including 43 patients diagnosed with epilepsy for the first time (main
      group) and 35 patients with the previous diagnosis of epilepsy (comparison
      group). Diagnosis was made according to ICD-10. Results. We observed a broad
      spectrum of persistent mental disorders, including negative disorders.
      Personality disorders and cognitive deficit were most significant negative
      disorders. Personality disorders included two opposite types: explosive
      epileptoid features with paranoiac signs and defensive disorder. Inertia, slow
      mobility, slowness of the rate of thought processes, the domination of
      egocentric, perseverative, visual-image thinking were characteristic of thought
      disorders. Conclusion. The authors suggest the systematic of these disorders. 

PMID- 24874310
TI  - [POEMS-syndrome: a literature review and case reports].
AB  - POEMS-syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, M-protein, and Skin
      Changes) is a rare nosological form occurred in patients with paraproteinemic
      hemoblastosis. Chronic progressive sensory-motor polyneuropathy is a key syndrome
      of the disease and it is a common reason for referral to neurologist. The paper
      presents data about POEMS-syndrome and own case reports with the analysis of
      disease features and results of examination.

PMID- 24874311
TI  - [Insulin resistance and arterial stiffness in patients with diabetes mellitus
      type 2 and cardiovascular autonomic neuropathy].
AB  - OBJECTIVE: To investigate parameters of insulin resistance and arterial stiffness
      in different stages of cardiovascular autonomic neuropathy in patients with
      diabetes mellitus type 2 (DM2). MATERIAL AND METHODS: The study involved 65
      patients with DM: 12 - without verified cardiovascular disease (CVD) and
      cardiovascular autonomic neuropathy (CAN), 14 - with subclinical, 18 -
      functional, 21 - functional-organic stage of CAN. A set of methods for assessment
      of cardiovascular system and main properties of arteries was implemented. RESULTS
      AND CONCLUSIONS: The development of CAN in patients with type 2 DM is accompanied
      with the increased level of immunoreactive insulin, insulin-resistance index. A
      trend towards increasing vascular wall stiffness in DM patients without CVD and
      CAN. The subclinical stage of CAN was characterized by increased pulse wave
      velocity in the aorta (PWV), aortic and brachial (AIXbr) augmentation indexes
      throughout the day, active and passive periods of day; functional - increased
      AIXbr during the night, PWV throughout the day, active and passive periods of day
      compared to subclinical stage; functional-organic - by increased and higher
      pathological values of vascular wall stiffness. Daily values of PWV and
      ambulatory arterial stiffness index in patients with functional-organic CAN were
      statistically significantly higher compared to groups with subclinical and
      functional stages of CAN.

PMID- 24874312
TI  - [A role of traumatic brain injury in the dynamics of combat posttraumatic stress
      disorder].
AB  - OBJECTIVES: To explore dynamics of clinical signs of posttraumatic stress
      disorder (PTSD) and their causal relationship with organic brain changes.
      MATERIALS AND METHODS: A longitudinal observational study of 87 combatants of the
      Karabakh war (1992-1994) was conducted in 2009-2011. Two groups of patients were
      singled out. The first group included 45 veterans with mild combat cranial/brain
      injury with the following development of PTSD; the second group consisted of 42
      veterans with organic brain lesions of traumatic origin. Somatic and neurological
      examination of patients and evaluation of their status using psychometric and
      other scales (CAPS, the Mississippi Scale for Combat-Related PTSD) were
      performed. RESULTS AND CONCLUSIONS: The analysis of patient's status at
      examination period and at the moment of injury demonstrated that PTSD patients,
      despite the relative reduction of posttraumatic symptoms, had higher level of all
      PTSD symptoms during the whole period of the disease (15-18 years) with the
      simultaneous aggravation of organic mental symptoms. In patients with organic
      brain lesions, the symptoms were more pronounced immediately after the traumatic
      event compared to the period of observation.

PMID- 24874313
TI  - [Influence of body position on intracranial pressure and cerebral hemodynamic in
      non-traumatic intracranial hemorrhages].
AB  - OBJECTIVE: Patient's body position is one of the most important principles of
      intensive therapy of intracranial hypertension syndrome. It is considered that
      the provision of the head end of a bed of 15-30 degrees is preferable for the
      majority of patients with cerebral pathology. We studied hemodynamic parameters
      at various tilt angles of the body in patients with non-traumatic intracranial
      hemorrhages. MATERIAL AND METHODS: Hemodynamic parameters (intracerebral
      pressure, cerebral perfusion, mean arterial pressure ) at various tilt angles
      were measured in 35 patients with intracranial hemorrhages. RESULTS: Using
      continuous monitoring of intracranial, cerebral perfusion and mean arterial
      pressure, we revealed the relationship between hemodynamic indicators and various
      tilt angles in patients with intracranial hemorrhages of non-traumatic genesis.
      CONCLUSION: Optimal positions of the head-end of a bed in different periods from
      disease onset are defined.

PMID- 24874314
TI  - [Poststroke cognitive, emotional impairment and sleep quality: efficience of
      treatment with melaxen].
AB  - OBJECTIVE: To study melatonin secretion and its correlations with poststroke
      cognitive, emotional impairment and sleep quality in the acute period of stroke
      and to assess treatment efficacy of melaxen. MATERIAL AND METHODS: We studied 96
      patients with acute stroke. A battery of tests and scales for assessment of
      neurological deficit, neuropsychological status and emotional impairment was
      used. The night urinary level of 6-sulfatoxymelatonin was assessed. The
      relationship between 6-sulfatoxymelatonin and cognitive, emotional status and
      sleep parameters was analyzed. RESULTS: The level of 6-sulfatoxymelatonin was
      decreased in the night urine. Patients with dysexecutive poststroke cognitive
      impairment had higher level of 6-sulfatoxymelatonin and patients with dysmnestic
      and mixed cognitive impairment had lower level of 6-sulfatoxymelatonin in
      comparison with patients with normal cognitive functions. Melaxen improved
      cognitive function and sleep parameters, reduced the level of anxiety in the
      early recovery period of stroke. CONCLUSION: A role of chronobiological processes
      in the development of clinical signs of stroke in the aspect of cognitive
      impairment is discussed.

PMID- 24874315
TI  - [Treatment of cognitive and non-cognitive symptoms in cerebrovascular disease].
AB  - OBJECTIVE: To study the therapeutic efficacy and safety of Ginkgo special extract
      EGb 761 in the treatment of cognitive and non-cognitive symptoms (anxiety,
      depression, sleep disorders, activity) in patients with discirculatory
      encephalopathy (DE) and cognitive impairment. MATERIAL AND METHODS: The study
      enrolled 45 patients with DE (mean age 60,8+/-5,9 years). Patients were
      randomized to treatment with EGb 761 (30 patients) or other drugs (15 patients).
      Patients underwent neurological examinations, along with cognitive and
      neuropsychological testing (FAB, MMSE, HADS and other tests). EGb 761 was used in
      dose 240 mg per day during 24 weeks. RESULTS: By the end of the study, the levels
      of anxiety and depression decreased (p<0,05) to the 12th and 24th week,
      respectively. CONCLUSION: The results indicate the efficacy and good tolerability
      of EGb 761 in the treatment of mental disorders in DE patients with cognitive
      impairment. The best effect was observed in relation to anxiety.

PMID- 24874316
TI  - [Clinical efficacy and pharmacoeconomic characteristics of the neuroprotection
      with low doses of cortexin in the treatment of acute ischemic stroke].
AB  - OBJECTIVE: To assess the efficacy of the cytoprotective neuropeptide cortexin in
      the complex treatment in acute and early rehabilitation stages of ischemic stroke
      (II). MATERIAL AND METHODS: A multicenter prospective double-blind placebo
      controlled trial has been carried out. Two hundreds and seventy-two patients with
      II have been enrolled in the trial. Cortexin was administered in low doses (10 mg
      three times a day intramuscular, using the following schemes: group 1: 2 courses
      of cortexin; group 2: 1 course of cortexin with the following course of placebo;
      group 3: two courses of placebo. The duration of treatment was 70 days. Patients
      were examined during 4 visits using clinical tests and instrumental methods.
      RESULTS: High efficacy and safety of cortexin in the complex treatment of
      patients with II has been shown. The best therapeutic effect was seen in group 1
      (two 10-day courses of cortexin). The results were confirmed by the
      pharmacoeconomic analysis of treatment tactics based on the estimation of "net
      monetary benefit". CONCLUSION: Cortexin is recommended for treatment and
      rehabilitation of patients with II.

PMID- 24874317
TI  - [Tenoxicam (texamen) in the treatment of acute cervicalgia: results of an open
      comparative trial].
AB  - OBJECTIVE: Acute cervical pain is one of the most common reasons for a visit to a
      doctor and temporal disability. We studied efficacy and safety of the nonsteroid
      anti-inflammatory drug tenoxicam (texamen) in the treatment of acute cervical
      pain in myofascial syndrome. MATERIAL AND METHODS: A trial included 50 people (42
      women and 8 men, mean age 42,2+/-6,8 years) with acute cephalgia. A main group
      (30 patients) received tenoxicam in dose 20 mg daily in the morning during 7 days
      with simultaneous therapeutic exercises with elements of postisometric relaxation
      of cervical muscles. A control group (20 patients) received myorelaxants and
      massage of a cervical-collar zone. RESULTS: The analgesic effect was more rapid
      in patients treated with texamen compared to controls. Statistically significant
      differences were seen in 1-3 days of treatment. In the main group, the analgesic
      effect long, only 16,6% of patients reported the aggravation of pain in the
      evening hours during the first day of treatment and 10% in the 2nd day; 23,3%
      patients of the main group used an additional dose of texamen, another nonsteroid
      anti-inflammatory drug (ibuprofen) or triptan to stop pain. CONCLUSION: The
      introduction of nonsteroid anti-inflammatory drugs, in particular texamen, in the
      complex treatment of acute cephalgia can significantly reduce pain syndrome.

PMID- 24874318
TI  - [Treatment of emotional and cognitive disorders in patients with chronic cerebral
      ischemia].
AB  - OBJECTIVE: To study clinical efficacy of the drug divasa in patients with chronic
      cerebral ischemia. MATERIAL AND METHODS: One hundred and forty-two patients, mean
      age 58,6+/-8,8 years, were treated during 11,9+/-0,2 weeks. Neurological
      examination and evaluation of a patient's status with psychometric scales were
      performed. RESULTS: The drug reduced anxiety, depressive and asthenic disorders
      beginning from the 4th week of treatment. The positive effect of treatment on
      cognitive functions appeared later. CONCLUSION: Divasa proved to be an effective
      drug in the complex treatment of patients with chronic disturbances of cerebral
      blood circulation.

PMID- 24874319
TI  - [Local invasive treatment of chronic pain].
AB  - The literature on methods of invasive local treatment of chronic pain was
      analyzed. We reviewed 14 publications including meta-analyses and systematic
      reviews. The use of regional anesthesia conducted by anesthesiologists in pain
      clinics demonstrated the evidence based efficacy of different types of peridural
      injections of local anesthetics with steroids in patients with root pain
      syndromes at cervical and lumbar levels. Therapeutic blockades of the occipital
      nerve is effective method of treatment of cervicogenic and cluster headache as
      well as occipital nerve neuralgia. There are clear indications of the efficacy of
      local injections in primary chronic cephalgia (migraine and headache of tension).
      The possibility of the abortion of the pain information flow in peripheral
      nociceptive pathways and, as a consequence, breaking the vicious circle is
      emphasized. Issues on the efficacy of local injections at trigger points in the
      treatment of chronic pain are highlighted. 

PMID- 24874320
TI  - [Clinical and neurophysiological objectification and evaluation of treatment
      efficacy in children with perinatal hypoxic-ischemic injury of the CNS].
AB  - OBJECTIVE: To objectify indications for treatment with pantogam in premature
      infants with perinatal hypoxic-ischemic injury of the CNS. MATERIAL AND METHODS:
      We studied 71 children, with GA (gestation age) 24-36 weeks (32,9+/-2,9 weeks),
      with perinatal hypoxic-ischemic injury of the CNS, I-II grades, and
      hyperexitability syndrome. The main group (33 patients) received pantogam in dose
      50 mg/kg/day at the adjusted age (AA) 36-40 weeks from the conception. The
      comparison group included 38 patients. EEG day sleep monitoring was performed
      before and at the end of treatment. RESULTS: Shortening of sleep cycle was
      observed in 78,8% children of the main group and in 78,9% of the comparison
      group. Duration of transitional sleep over 1 min was 78,79% and 81,58%. At AA 44
      46 weeks, the frequency of sleep disorders decreased to 45,45% (p=0,012) and
      52,63% (p=0,05). Duration of transitional sleep over 1 min was 45,45% and 65,79%.
      Duration of the latent period of the 2nd stage of slow wave sleep was 6,4+/-2,57
      and 12,5+/-7,18 min (p=0,0004). CONCLUSION: The treatment reduced sleep
      disorders, changed the duration of transitional sleep stage and latent period of
      the 2nd stage of slow wave sleep.

PMID- 24874321
TI  - [A role of glutamate decarboxylase in Alzheimer's disease].
AB  - OBJECTIVE: To evaluate the levels of the main GABA synthetic enzyme, glutamate
      decarboxylase (represented by two isoforms, GAD65 and GAD67) in the cerebellum
      cortex of patients with Alzheimer's disease (AD) and mentally healthy subjects.
      MATERIALS AND METHODS: Samples of the cerebellum cortex from 13 mentally healthy
      subjects (the control group) and 13 patients with AD were studied. Samples
      obtained after autopsy were frozen and stored at -80  degrees C. The groups are
      matched by sex, age, postmortem interval and cause of death. Protein extracts
      from cerebellum tissues were obtained after removing of nuclei and cell debris by
      centrifugation and treatment of the obtained fractions with detergent (SDS).
      Relative amounts of GAD65 and GAD67 were determined using SDS-PAAG
      electrophoresis with the following semi-quantitative ECL-Western-immunoblotting
      with chemiluminescence detection. RESULTS: The amounts of both isoenzymes (GAD65
      and GAD67) were significantly reduced in AD samples. CONCLUSION: The decreased
      amount of both glutamate decarboxylase isoenzymes suggests the decreased
      synthesis of neurotransmitter and basic GABA pools that indicates insufficient
      functioning of the GABA system in the cerebellar cortex of AD patients.

PMID- 24874322
TI  - [Degenerative and regenerative changes in hippocampus in postnatal ontogenesis].
AB  - OBJECTIVES: To study the degenerative and regenerative age-related changes in
      human hippocampus. MATERIALS AND METHODS: An immunohistochemical investigation of
      the hippocampus was carried out in 50 people, aged 25-89 years, who died for
      different reasons not connected with the cerebral injury or pathology. Expression
      of the following markers was determined: tau-protein, GFAP, CD105/endoglin, E
      selectin, NCAM, Cdk2. Statistical analysis was performed with the program package
      Biostat. RESULTS AND CONCLUSIONS: Gliogenesis and vasculogenesis processes were
      active in old and very old age. They may be conditioned by ischemic cerebral
      injuries and accompany the development of Alzheimer's disease.

PMID- 24874323
TI  - [New classification and standards in treatment of migraine].
AB  - Diagnosis of migraine is performed according to the International Classification
      of Headache Disorders (ICHD). A current version is ICHD-2004 (2 ed.). A new
      addition of ICHD beta-version has been published in 2013. This article reviews
      the structure of the new classification and main criteria of different types of
      headache. Main treatment approaches and features of some drugs for treatment of
      headache and migraine are considered. Special attention is focused on xefocam, a
      nonsteroidal anti-inflammatory drug. 

PMID- 24874324
TI  - [Migration of a nociogenic zone in human somatosensory system].
AB  - The article reviews the process of migration of nociogenic zones and principles
      of their integrative switching - off from the point of systematic approach and
      the informational-structural theory of pain. The phenomenon of migration of
      nociogenic zones underlies the development of clinical manifestations of pain. 

PMID- 24874326
TI  - [Efficacy and safety of valdoxan in patients with irritable bowel syndrome].
AB  - OBJECTIVES: To evaluate the efficacy and safety of the antidepressant valdoxan in
      irritable bowel syndrome (IBS) with comorbid mild and moderate depression.
      METHODS: Twenty-eight patients with IBS and depression without psychotic symptoms
      were studied using clinical examination and psychometric scales. RESULTS: A
      significant reduction in psychopathological symptoms, along with the improvement
      of health status, was recorded for most patients treated with valdoxan (25-50
      mg/night) in the end of the 1st week. CONCLUSION: Valdoxan has a good
      tolerability and safety profile, does not exert any negative effect on the IBS
      course and provides a high level of compliance.

PMID- 24874325
TI  - [Indices of cerebrovascular reactivity in patients with diabetes mellitus
      complicated with cardiovascular autonomic neuropathy].
AB  - OBJECTIVES: To investigate cerebrovascular reactivity in patients with diabetes
      mellitus complicated with cardiovascular autonomic neuropathy. METHODS: We
      examined 34 patients with diabetes mellitus (9 men and 25 women). Functional
      tests (hypercapnic, cold, orthostatic and others) and indices of cerebral
      hemodynamics were used for the evaluation of cerebrovascular reactivity. RESULTS:
      There was a decrease in the rate of cerebral blood flow and the deterioration of
      cerebrovascular reserves in the middle cerebral artery of patients with diabetes
      mellitus with cardiovascular autonomic neuropathy and without it in comparison
      with the appropriate indices of healthy people. At the same time, no differences
      were found between diabetic patients with - and without cardiovascular autonomic
      neuropathy. CONCLUSIONS: The abnormalities of the cerebrovascular reactivity can
      play an important role in the pathogenesis of cerebrovascular disease in this
      group of patients.

PMID- 24874327
TI  - [Diagnosis of paraneoplastic polyneuropathy in patients with breast cancer and
      small cell lung cancer].
AB  - OBJECTIVES: To study possibilities of immunological and electrophysiological
      methods for the diagnosis of paraneoplastic polyneuropathy in cancer. METHODS: We
      studied 88 cancer patients using electromyography and immunological assay (serum
      neuronal antibodies). RESULTS: A symmetrical, distal, sensory-motor, axonal
      demyelinating form of polyneuropathy can develop in breast cancer and small cell
      lung cancer. Onconeural antibodies were detected in the serum of more than half
      of study participants as well as in some healthy donors. Symptoms of
      polyneuropathy appeared earlier than the diagnosed tumor. CONCLUSION: The
      diagnostic value of the methods used for the early diagnosis of breast cancer and
      small cell lung cancer is emphasized.

PMID- 24874328
TI  - [Efficiency of mexidol in patients with endocrine polyneuropathy].
AB  - OBJECTIVE: To evaluate the efficacy of mexidol and necessity of using it in
      patients with endocrine polyneuropathies caused by primary hypothyroidism (PPHT).
      MATERIALS AND METHODS; We have examined 51 patients with confirmed diagnosis of
      PPHT and assessed their neurological status and indicators of metabolic
      homeostasis before and after treatment. Electroneuromyography (ENMG) was
      performed to assess the status of the peripheral nervous system. RESULTS: The
      results indicate the presence of endocrine disorders of obligate metabolic
      homeostasis in patients with polyneuropathies. Antioxidants, in particular,
      mexidol, in a complex with other drugs can be used in the treatment of these
      disorders. Worsening of ENMG-parameters, demonstrating a trend towards the
      normalization in response to treatment antioxidants, are characteristics of this
      pathology. CONCLUSION: The efficacy of mexidol in patients with PPHT has been
      confirmed.

PMID- 24874329
TI  - [Benign paroxysmal positional vertigo in a female with arterial hypertension and
      meningioma].
AB  - Diagnosis of benign paroxysmal positional vertigo (BPPV) often causes
      difficulties, in particular, in elderly people with concomitant diseases. The
      article presents a case of a 77 year-old woman with BPPV. A patient's complaint
      on vertigo was mistakenly diagnosed as brain ischemia because the patient had
      long suffered from uncontrolled arterial hypertension. MRI-study revealed
      leucoaraiosis and one lacuna as well as a meningioma which was mistakenly linked
      to vertigo. The diagnosis of BPPV, use of Epley maneuver with the following
      vestibular exercises resulted in complete stopping of vertigo. Effective
      treatment of arterial hypertension with the normalization of arterial pressure,
      use of aspirin and statins reduced the risk of stroke. Exclusion of BPPV is
      needed in all cases of vertigo with unclear etiology. 

PMID- 24874330
TI  - [Electric status epilepticus in sleep (case report)].
AB  - Electric status epilepticus in sleep (ESES) syndrome is the partially reversible,
      age-dependent children's epileptic encephalopathy with continuous spike-wave
      complexes in a slow sleep phase. It is a nonspecific electrographic phenomenon in
      many epileptic syndromes. It can be a single indicator of the epileptic nature of
      disorders and a marker of epileptic encephalopathy. A sleep EEG should be
      performed in children with autistic, speech, behavioral disorders to specify
      their etiology and prescribe pathogenetic treatment. 

PMID- 24874331
TI  - [Developmental dysphasia and epileptiform EEG activity in children].
AB  - Objective. To study the electrical activity of the brain in children with
      developmental dysphasia (alalia). Material and methods. We analyzed the EEGs of
      65 children with developmental dysphasia, including 48 boys and 17 girls, aged
      from 3 to 4 years 11 months. General speech underdevelopment (GSU) of the 1st
      level (with active vocabulary less than 15-20 words) was found in 31 children and
      GSU of the 2nd level (with active vocabulary of 20-50 words) - in 34 children. To
      specify the changes in the brain electrical activity, we conducted video-EEG
      monitoring during sleep and waking states in 27 patients. Results. Focal
      epileptiform EEG changes with no concomitant paroxysmal symptoms were recorded in
      12,3% of children with dysphasia. The epileptiform activity was more frequent in
      GSU of the 1st level (5 (16.1%) patients) than in GSU of the 2nd level (3 (8.8%)
      patients). Benign epileptiform discharges of childhood with low index were
      identified in 2 (6,5%) children with GSU of the 1st level and in1 (2,9%) child
      with GSU of the 2nd level; low index spike-waves were recorded in 3 (9,7%)
      children with GSU of the 1st level and in 2 (5,9%) with GSU of the 2nd level.
      Conclusion. The data allow to clarify the frequency of epileptiform EEG activity
      in those children with developmental dysphasia, who do not have autism or history
      of seizures. The differential diagnosis with rare epileptic encephalopathies is
      needed, such as epilepsy with electrical status epilepticus during slow sleep
      (ESES) and Landau-Kleffner syndrome. 

PMID- 24874332
TI  - [Therapeutic pathomorphosis of epilepsy: the results of treatment with
      antiepileptic drugs of different generations].
AB  - Objective. Therapeutic pathomorphosis was studied basing on the results of
      treatment with antiepileptic drugs (AED) of different generations with the
      account of epilepsy etiology: symptomatic (SE), cryptogenic (CE) and idiopathic
      (IE). Material and methods. A long-term (8.5+/-3.0 years) prospective study
      included 404 patients, aged - 36.8+/-8.4 years, with SE (236 (58.4%) patients),
      CE (130 (32.2%) patients) and IE (38 (9.4%) patients). Results. Regardless of the
      causes of the disease, the most effective was monotherapy with new drugs
      (r<0.01), slightly less effective was monotherapy with traditional
      anticonvulsants, and then - treatment with combinations of traditional and new
      drugs. Positive therapeutic pathomorphosis was noted in IE (84.2% of patients in
      remission) in comparison with CE (p<0.05) and SE (p<0.01). In SE patients, the
      best treatment result (positive therapeutic pathomorphosis) was observed in those
      with vascular, including post-stroke, epilepsy, in which the remission of
      seizures was observed in 86.7% of cases (p<0.01). Negative therapeutic
      pathomorphosis of the disease with the development of pharmacoresistance was
      noted in epilepsy after traumatic brain injuries (p<0.05) and in mesial temporal
      sclerosis (p<0.05). Conclusion. The group of relatively resistant patients
      (14.4%) with fluctuating (remitting - relapsing) course of the disease was
      described. 

PMID- 24874333
TI  - [The effect of antiepileptic therapy on the level of hormones in the blood serum
      of girls with epilepsy].
AB  - Objective. To investigate the effect of modern antiepileptic drugs on the
      hormonal profile of girls with epilepsy. Materials and methods. Levels of thyroid
      stimulating hormone (TSH), thyrogiobulin antibodies (a/b TG), triiodothyronine
      (T3), thyroxine (T4), parathyroid hormone (P) and cortisol (C) were determined in
      the blood of 50 girls with epilepsy, aged from 8 to 17 years. In 19 girls,
      repeated measures of TSH, a/b TG, T3, T4 and C were taken 2-12 months after the
      first study. Valproate, carbamazepine, and topamax were used for treatment.
      Results. The highest content of TSH was found in girls, aged 8-17 years, treated
      with valproate. The presence of a/b TG was recorded in patients who did not
      receive antiepileptic drugs. T3, T4 and P levels were found in patients treated
      with phenobarbital or benzonal, topamax and valproate, respectively. C was
      detected in girls, aged 8-13 years, treated with phenobarbital or benzonal and in
      girls, aged 14-17 years, treated with trileptal. Repeated measures revealed the
      changes in all hormones in 64.86% of patients. Conclusion. Significant
      differences in the content of all hormones were found in girls treated with
      various antiepileptic drugs. Choice of drug, dosage and its correction should be
      made taking into account its impact on children's hormonal profile. 

PMID- 24874335
TI  - [Rational polytherapy of epilepsy in children].
AB  - About 30% of patients with epilepsy are resistant to pharmacological treatment.
      These patients benefit from combinational therapy with two or more antiepileptic
      drugs (AEDs). The management of resistant epileptic patients with AEDs
      combinations is based on the pharmacokinetic and pharmacodynamic interactions
      between AEDs. The article reviews the data on interactions between widely used
      AEDs. 

PMID- 24874334
TI  - [Fine motor and self-development assessment of preschool children with epilepsy].
AB  - Objective. To assess fine motor and self-care skills in preschool children with
      epilepsy. Material and methods. The study included 22 children, 12 girls (54.5%)
      and 10 boys (45.5%), mean age 41.5+/-19.9 months. Children were tested with DISC
      and Munchen tests. Results and conclusion. Among preschool children with
      epilepsy, 50% have impaired and 22.7% - delayed development of fine motor skills.
      The mean coefficient of fine motor skills was 59.0+/-28.1. Among preschool
      children with epilepsy, 36.4% have impaired and 45.5% - delayed development of
      self-development skills. The coefficient of self-care skills was 57.8+/-26.1.
      DISC and Munchen tests for evaluation of small motor and self-care skills are
      equivalent for assessment in children with epilepsy (p<0.001). Self-care skills
      were more often disturbed (p<0.05) among children older than 3 years and among
      boys. Children with psychiatric and movement disorders (72.7%) more frequently
      have both impaired self-care and fine motor skills (p<0.05). 

PMID- 24874336
TI  - [Secondary epileptogenesis in the immature brain: a role of GABA].
AB  - Clinical studies show that the probability of recurrent epileptiform discharges
      and formation of an epileptic focus (epileptogenesis) in young children is much
      higher than in adults. Repetitive epileptiform discharges and their potential
      contribution to the mechanisms of the development of the epileptic focus - an
      important object of clinical and scientific research. This review is based on the
      data from animal studies, and summarizes the current understanding of the
      mechanisms underlying the increased excitability of the immature brain, the
      formation of a secondary epileptogenic focus, and the functional changes of
      neurons due to deleterious effects of repetitive epileptiform discharges on the
      excitation and inhibition in the immature neuronal networks. The review discusses
      the relevance of experimental data in light of the general mechanisms of
      epileptogenesis in infants and identifies the gaps in current scientific
      knowledge, including the relationship between the data obtained in animal studies
      and processes underlying human acquired epilepsy. 

PMID- 24874338
TI  - [Epileptic seizures in patients with systemic rheumatic disorders].
AB  - Systemic rheumatic disorders affect multiple organ systems. Seizures are among
      the most common neurological manifestation and occasionally can be the presenting
      symptom. This article reviews the literature on the mechanisms underlying
      seizures in systemic rheumatic disorders and predisposing factors, including
      vascular disease (e.g., prothrombotic state, anticardiolipin antibody, emboli,
      vasculitis), antineuronal antibodies, immune complexes, cytokines, metabolic
      disorders, infection, and therapy. Diagnostic and therapeutic strategies must be
      individualized for both the disorder and the patient. 

PMID- 24874337
TI  - [Epileptic encephalopathy with continuous spikes and waves during sleep (CSWS): a
      review].
AB  - Epileptic encephalopathy (EE) with continuous spikes and waves during sleep
      (CSWS) (epilepsy with electric epileptic status during slow sleep phase or
      encephalopathy with electric epileptic status during slow sleep phase) is
      partially reversible age-dependent epileptic encephalopathy. It is characterized
      by a triad of symptoms: seizures, neurocognitive regression, and an
      electroencephalography pattern of electrical status epilepticus during sleep.
      This rare condition occurs in 0,5% of children and adolescents with epilepsy.
      Seizures usually start when the child is 2-4 years old. Several stages in CSWS
      are identified: dormant stage, prodromal stage, acute stage, and residual stage.
      EE epileptiform activity may be focal, multifocal, unilateral, asymmetric or
      symmetric bilateral, and diffusive. Treatment goals of CSWS include not only
      improved seizure control, but also a significant reduction in EEG epileptiform
      activity. Benzodiazepines and steroids are most effective. 

PMID- 24874339
TI  - [Possibilities of using intravenous forms of antiepileptic drugs in epileptic
      seizures].
AB  - The literature data on using intravenous forms of AEDs that expand treatment
      possibilities for patients with epilepsy are presented. AEDs can be used in
      different situations, when patients are not able to take AEDs in per os. These
      situations can include seizure emergencies (recurrent seizures, clusters, status
      epilepticus), caused by disease decompensation; acute symptomatic seizures;
      perioperative preparation in the case of surgery; dysphagia; gastrointestinal
      problems; psychiatric disorders, and others. This article is based on a review of
      International and Russian expert consensus practice guidelines for management of
      clinical situations mentioned above. The authors present data on available
      Russian parenteral forms of drugs used today (valproats, levetiracetam,
      lacosamide, diazepam, midazolam, propofol, thiopental potassium). It has been
      concluded that an ideal intravenous AED should be highly effective, acts fast,
      has no severe adverse effects, has low drug-drug interactions, does not require
      frequent plasma concentration monitoring, and should be easily switched to a per
      os form without any additional titration. The importance of separate treatment
      approaches on different stages of medical help is emphasized. The choice of drug
      used can be influenced by a particular clinical situation,
      indications/contraindications, the recommended infusion speed, side effects,
      possible drug-drug interactions with other AEDs and other drugs used for the
      treatment of concomitant diseases, availability of a particular drug at the
      moment and the level of a physician's knowledge of usage of intravenous forms of
      AEDs. 

PMID- 24874340
TI  - [Epilepsy and society: a new model of attitudes].
AB  - Epilepsy is a multifaceted problem including not only medical but economical,
      social and ethical aspects. Its solving depends on societal attitudes toward as
      the problem per se as well as to patients with epilepsy. Methodological grounds
      of the attitude and models of physician - patient interactions determined by this
      attitude are analyzed. 

PMID- 24874341
TI  - [Migraine and epilepsy: an attempt to analyze disorders in Pontius Pilate in the
      romance "Master and Margarita" by M. Bulgakov].
AB  - This article reviews the literature on the relation between migraine and
      epilepsy. The commonality of pathogenetic mechanisms of these diseases is
      emphasized. As an example, the author analyzed neurological disorders in Pontius
      Pilate in M. Bulgakov's romance "Master and Margarita". These disorders are
      traditionally considered as an attack of migraine with olfactory aura. The author
      suggests the epileptic character of these disorders. 

PMID- 24874342
TI  - [An expert meeting on epileptology "Difficulties in the treatment of epilepsy in
      Russia"].

PMID- 24874344
TI  - Interval appendectomy in children clinical outcomes, financial costs and patient
      benefits.
AB  - BACKGROUND: Elective interval appendectomy (IA) is traditionally advocated for
      the management of appendiceal mass (AM) in children. Surgeons have debated the
      evidence and 'risks' vs. 'benefits' to support IA. There are currently no
      randomised controlled trials and guiding best practice and financial costings for
      IA are lacking. We herein report clinical outcomes, patient benefits and tariff
      charges linked with the provision of IA at a regional UK paediatric surgical
      centre. METHODS: Hospital case records of patients with AM were identified using
      pathology records and hospital admission codes during a 15-year period (1997
      2011). Tariff costs (L Sterling) were calculated for all admissions during the
      era 2007-2011. RESULTS: 69 children were admitted with AM (61% female, median age
      10.5 years, range 2.1-16 years). Median initial hospital stay with resolution of
      symptoms was 8 days (range 3-14 days). 61 children (88%) had elective IA (median
      interval 76 days, range 29-230 days). Eight (12 %) patients required emergency
      readmission for early appendectomy (median interval 21 days, range 6-51 days).
      Hospital stay for emergency readmission appendectomy in these children was
      significantly longer than IA (median 6 vs. 3 days, p < 0.01). Laparoscopic
      appendectomy vs. 'open' appendectomy was associated with shorter length of stay
      in the IA cohort (median 3 vs. 2 days p < 0.01). No intra-operative morbidity was
      recorded in the study with only a single case developing a post-operative wound
      infection. Median cost for IA was L1,936. Costings were higher in the emergency
      appendectomy group-L2,171 vs. 1,936; p = 0.09, NS. CONCLUSION: Only 12% of
      children at this centre develop recurrent appendicitis after primary admission
      with AM. Interval and emergency appendectomy were associated with low morbidity.
      Parents should be informed that IA may be 'non essential' surgery. Paediatric
      surgeons not routinely advocating IA can potentially save the NHS L1,936 per
      patient. Future randomised studies are warranted to confirm or refute these
      findings.

PMID- 24874345
TI  - Microhydration of contact ion pairs in M(2+)OH(-)(H2O)(n=1-5) (M = Mg, Ca)
      clusters: spectral manifestations of a mobile proton defect in the first
      hydration shell.
AB  - Vibrational predissociation spectra of D2-"tagged" Mg(2+)OH(-)(H2O)n=1-6 and
      Ca(2+)OH(-)(H2O)n=1-5 clusters are reported to explore how the M(2+)OH(-) contact
      ion pairs respond to stepwise formation of the first hydration shell. In both
      cases, the hydroxide stretching frequency is found to red-shift strongly starting
      with addition of the third water molecule, quickly becoming indistinguishable
      from nonbonded OH groups associated with solvent water molecules by n = 5. A
      remarkably broad feature centered around 3200 cm(-1) and spanning up to ~1000 cm(
      1) appears for the n >= 4 clusters that we assign to a single-donor ionic
      hydrogen bond between a proximal first solvent shell water molecule and the
      embedded hydroxide ion. The extreme broadening is rationalized with a theoretical
      model that evaluates the range of local OH stretching frequencies predicted for
      the heavy particle configurations available in the zero-point vibrational wave
      function describing the low-frequency modes. The implication of this treatment is
      that extreme broadening in the vibrational spectrum need not arise from thermal
      fluctuations in the ion ensemble, but can rather reflect combination bands based
      on the OH stretching fundamental that involve many quanta of low-frequency modes
      whose displacements strongly modulate the OH stretching frequency. 

PMID- 24874343
TI  - Antegrade continent enema procedures performed prior to starting school may
      improve functional stooling and quality of life.
AB  - PURPOSE: A major research gap is determining the best age to perform an
      appendicostomy or cecostomy. This study hypothesizes that performance of
      appendicostomy/cecostomy prior to starting school (<6 years) would improve
      functional stooling and quality of life (QOL). METHODS: Patients who underwent
      appendicostomy/cecostomy for bowel management between 2003 and 2013 were
      retrospectively identified. Families were prospectively surveyed regarding
      current stooling habits (17 items) and a (7 item) pediatric QOL survey. Lower
      stooling survey scores represent better bowel control. Higher QOL scores
      indicated better quality. The primary outcome was to correlate age of
      appendicostomy/cecostomy to QOL score. Statistics were performed using paired,
      unpaired t tests, and Chi-square. p Values <=0.05 were considered significant.
      RESULTS: 35 patients underwent placement of appendicostomy/cecostomy. Fourteen
      (40%) patients/families were prospectively contacted (<6, n = 6; >6, n = 8).
      Stooling scores (15.17 +/- 1.35 vs. 22.25 +/- 1.70; for <6 vs. >6 years old, p =
      0.009) and continence scores (6.33 +/- 1.45 vs. 11.13 +/- 1.64; p = 0.06), at
      time of contacting families, were significantly better in those undergoing
      appendicostomy/cecostomy in the <6 group. Pre-procedure QOL scores for the two
      groups were similar (p = 0.89). Post-procedure QOL significantly increased to the
      good subcategory for both age groups; however improvement was significantly
      better in the <6 age group vs. >=6 group: 6.33 +/- 0.92 vs. 3.13 +/- 0.91 points
      (p = 0.03). A secondary parent survey showed significantly more families wished
      an appendicostomy/cecostomy were done earlier in the >6 vs. <6 group (87.5 vs.
      33%; p = 0.04). CONCLUSION: Early placement of cecostomy or appendicostomy as
      part of a bowel management program may contribute to improved QOL and functional
      stooling.

PMID- 24874346
TI  - Association Between Pubertal Onset and Symptoms of ADHD in Female University
      Students.
AB  - OBJECTIVE: This exploratory study investigated how the timing of female pubertal
      maturation was associated with the symptoms of ADHD in a non-clinical female
      undergraduate sample (N = 253). METHOD: Participants (Mage = 20.2 +/- 1.7 years)
      completed a set of self-report rating scales examining pubertal onset and ADHD
      symptoms and related deficits. RESULTS: Logistic regression analysis indicated
      that early puberty was associated with elevation in symptoms, including
      difficulties in attention (odds ratio [OR] = 1.270, p = .019), emotion regulation
      (OR = 1.070, p = .038), and more risky behavior (OR = 1.035, p = .045). That is,
      increased symptom endorsement was shown to significantly help classify those who
      reported having an earlier pubertal onset relative to their peers. CONCLUSION:
      Findings highlight the potential role of sex hormones during puberty in
      explaining the gender differences in prevalence rates of ADHD and symptom
      profiles.

PMID- 24874347
TI  - Pilot randomized controlled trial of dialectical behavior therapy group skills
      training for ADHD among college students.
AB  - OBJECTIVE: ADHD affects between 2% and 8% of college students and is associated
      with broad functional impairment. No prior randomized controlled trials with this
      population have been published. The present study is a pilot randomized
      controlled trial evaluating dialectical behavior therapy (DBT) group skills
      training adapted for college students with ADHD. METHOD: Thirty-three
      undergraduates with ADHD between ages 18 and 24 were randomized to receive either
      DBT group skills training or skills handouts during an 8-week intervention phase.
      ADHD symptoms, executive functioning (EF), and related outcomes were assessed at
      baseline, post-treatment, and 3-month follow-up. RESULTS: Participants receiving
      DBT group skills training showed greater treatment response rates (59-65% vs. 19
      25%) and clinical recovery rates (53-59% vs. 6-13%) on ADHD symptoms and EF, and
      greater improvements in quality of life. CONCLUSION: DBT group skills training
      may be efficacious, acceptable, and feasible for treating ADHD among college
      students. A larger randomized trial is needed for further evaluation.

PMID- 24874348
TI  - Efficacy, Safety, and Tolerability of a Novel Methylphenidate Extended-Release
      Oral Suspension (MEROS) in ADHD.
AB  - OBJECTIVE: To test whether an optimal dose of Quillivant XR (methylphenidate
      extended-release oral suspension [MEROS]) would significantly reduce symptoms of
      ADHD in children. METHOD: A randomized, double-blind, placebo-controlled, cross
      over, efficacy, safety, and tolerability study of MEROS in 45 children aged 6 to
      12 years (open-label dose-optimization phase, followed by double-blind cross-over
      period). RESULTS: MEROS was significantly more efficacious than placebo during
      double-blind cross-over laboratory classroom days (Swanson, Kotkin, Agler, M
      Flynn, and Pelham Rating Scale and Permanent Product Measure of Performance).
      During the open-label phase, improvements were observed in scores of ADHD Rating
      Scale-IV, and Clinical Global Impression-Severity and -Improvement Scales. No
      occurrences of suicidal ideation or behavior were recorded; the most common open
      label treatment-emergent adverse events were typical of stimulant use: decreased
      appetite, insomnia, and abdominal pain. CONCLUSION: MEROS was efficacious in the
      treatment of children aged 6 to 12 years with ADHD, with a safety profile similar
      to that of other extended-release methylphenidate pharmacotherapies.

PMID- 24874349
TI  - Alpha-amylase from wheat (Triticum aestivum) seeds: its purification, biochemical
      attributes and active site studies.
AB  - Glycosylated alpha-amylase from germinated wheat seeds (Triticum aestivum) has
      been purified to apparent electrophoretic homogeneity with a final specific
      activity of 1,372 U/mg. The enzyme preparation when analysed on SDS-PAGE,
      displayed a single protein band with Mr 33 kDa; Superdex 200 column showed Mr of
      32 kDa and MS/MS analysis further provided support for these values. The enzyme
      displayed its optimum catalytic activity at pH 5.0 and 68  degrees C with an
      activation energy of 6.66 kcal/mol and Q10 1.42. The primary substrate for this
      hydrolase appears to be starch with Km 1.56 mg/mL, Vmax 1666.67 U/mg and kcat 485
      s(-1) and hence is suitable for application in starch based industries. Thermal
      inactivation of alpha-amylase at 67  degrees C resulted in first-order kinetics
      with rate constant (k) 0.0086 min(-1) and t1/2 80 min. The enzyme was susceptible
      to EDTA (10mM) with irreversible loss of hydrolytic power. In the presence of
      1.0mM SDS, the enzyme lost only 14% and 23% activity in 24 and 48 h,
      respectively. Chemical modification studies showed that the enzyme contains
      histidine and carboxylic residues at its active site for its catalytic activity
      and possibly conserved areas.

PMID- 24874350
TI  - Determination of grain protein content by near-infrared spectrometry and
      multivariate calibration in barley.
AB  - Grain protein content (GPC) is an important quality determinant in barley. This
      research aimed to explore the relationship between GPC and diffuse reflectance
      spectra in barley. The results indicate that normalizing, and taking first-order
      derivatives can improve the class models by enhancing signal-to-noise ratio,
      reducing baseline and background shifts. The most accurate and stable models were
      obtained with derivative spectra for GPC. Three multivariate calibrations
      including least squares support vector machine regression (LSSVR), partial least
      squares (PLS), and radial basis function (RBF) neural network were adopted for
      development of GPC determination models. The Lin_LSSVR and RBF_LSSVR models
      showed higher accuracy than PLS and RBF_NN models. Thirteen spectral wavelengths
      were found to possess large spectrum variation and show high contribution to
      calibration models. From the present study, the calibration models of GPC in
      barley were successfully developed and could be applied to quality control in
      malting, feed processing, and breeding selection. 

PMID- 24874351
TI  - Buffering colour fluctuation of purple sweet potato anthocyanins to acidity
      variation by surfactants.
AB  - Anthocyanins are intriguing natural pigments with beneficial bioactivities and
      their colour is extremely susceptible to acidity variation. Minimisation of
      colour fluctuation is essential to maintain quality consistency in food industry.
      A new strategy employing surfactants to mimic encapsulation was attempted with
      typical anionic, cationic and nonionic surfactants and proved effective although
      the traditional copigmentation method was inactive. The exceptional colour
      fluctuation buffering effect of anionic surfactants especially sodium dodecyl
      sulphate (SDS) was revealed and then carefully analysed by colorimetric and
      spectroscopic methods. The outstanding activity of SDS presumably resulted from
      effective shielding of anthocyanins from external acidity through strong
      interaction with the positively charged flavylium cations owing to its anionic
      nature. These results suggest SDS is a valuable additive for buffering colour
      fluctuation of anthocyanins. The strategy of surfactant will be useful for
      buffering colour fluctuation of natural colourants. 

PMID- 24874352
TI  - Gold nanoparticle aggregation-based colorimetric assay for beta-casein detection
      in bovine milk samples.
AB  - Traditional Kjeldahl method, used for quality evaluation of bovine milk, has
      intrinsic defects of time-consuming sample preparation and two analyses to
      determine the difference between non-protein nitrogen content and total protein
      nitrogen content. Herein, based upon antibody functionalized gold nanoparticles
      (AuNPs), we described a colorimetric method for beta-casein (beta-CN) detection
      in bovine milk samples. The linear dynamic range and the LOD were 0.08-250 MUg
      mL(-1), and 0.03 MUg mL(-1) respectively. In addition, the real content of beta
      CN in bovine milk was measured by using the developed assay. The results are
      closely correlated with those from Kjeldahl method. The advantages of beta-CN
      triggered AuNP aggregation-based colorimetric assay are simple signal generation,
      the high sensitivity and specificity as well as no need of complicated sample
      preparation, which make it for on-site detection of beta-CN in bovine milk
      samples.

PMID- 24874354
TI  - An electrochemical aptasensor based on gold nanoparticles dotted graphene
      modified glassy carbon electrode for label-free detection of bisphenol A in milk
      samples.
AB  - A simple and label-free electrochemical aptasensor for bisphenol A (BPA)
      determination was developed based on gold nanoparticles dotted graphene (GNPs/GR)
      nanocomposite film modified glassy carbon electrode (GCE). The electrochemical
      probe of ferricyanide was used to investigate the interactions between aptamer
      and BPA. The resulting GNPs/GR layer exhibited good current response for BPA
      detection. The highly conductive and biocompatible nanostructure of GNPs/GR
      nanocomposite was characterised by atomic force microscope (AFM), scanning
      electron microscopy (SEM) and cyclic voltammetry (CV). The peak current change
      (DeltaI) of ferricyanide was linear with the concentration of BPA in the range
      from 0.01 MUM to 10 MUM with the detection limit of 5 nM. The proposed aptasensor
      is rapid, convenient and low-cost for effective sensing of BPA. Particularly, the
      aptasensor was applied successfully to determine BPA in milk products, and the
      average recovery was 105%.

PMID- 24874353
TI  - Determination of glycinin in soybean and soybean products using a sandwich enzyme
      linked immunosorbent assay.
AB  - This study performs a sandwich ELISA for detection of trace amounts of glycinin
      in soybean products. We designed a soy-free mouse model to produce anti-glycinin
      monoclonal antibodies with high affinity and specificity. Using the monoclonal
      antibody as coating antibody, with the rabbit anti-glycinin polyclonal antibody
      as a detected antibody, the established sandwich ELISA showed high specificity
      for glycinin with minimum cross-reactions with other soy proteins. The practical
      working range of the determination was 3-200 ng/mL with detection limit of 1.63
      ng/mL. The regaining of glycinin in spiked soybean samples were between 93.8% and
      103.3% with relative standard deviation less than 8.3% (intra-day) and 10.5%
      (inter-day). The developed assay was used in analysing 469 soybean samples and
      five soybean products under different processing. The assay provides a specific
      and sensitive method for screening of glycinin and allows for further
      investigation into hypersensitive mechanisms to soybean proteins.

PMID- 24874356
TI  - Changes of isoflavones and protein quality in soymilk pasteurised by ultra-high
      pressure homogenisation throughout storage.
AB  - Ultra high pressure homogenisation (UHPH) is an emerging technology to obtain
      fine and stable soymilk emulsions. Very little information is available about the
      stability of this kind of product during storage. Changes of isoflavone profile,
      protein digestibility and lysine availability in pasteurised-UHPH soymilks were
      studied for 21 days at 4  degrees C in comparison to heat-pasteurised soymilks.
      Neither heat nor UHPH treatments affected the isoflavone profile, as the
      percentage of each chemical form, in comparison with unprocessed-soymilk. During
      storage, there was a conversion of isoflavone forms to aglycones, being higher in
      heat-processed samples. In addition, UHPH samples showed a lesser percentage of
      blocked lysine during storage. No differences were observed in the evolution of
      protein digestibility among samples. Therefore, UHPH treatment seems to produce a
      better product, due to lower amounts of aglycones, and higher protein nutritional
      quality than heat treatment.

PMID- 24874355
TI  - Immunoassays for trifloxystrobin analysis. Part II. Assay development and
      application to residue determination in food.
AB  - Immunochemical assays constitute complementary analytical methods for small
      organic molecule determination. We herein describe the characterisation and
      optimisation of two competitive enzyme-linked immunosorbent assays in different
      formats using monoclonal antibodies to the Quinone outside inhibitor (QoI)
      fungicide trifloxystrobin. Antibody selectivity was evaluated using a variety of
      agrochemicals and the main trifloxystrobin metabolite. Acceptable tolerance of
      the immunoassay to methanol, ethanol, and acetonitrile was observed in all cases,
      whereas a dissimilar influence of buffer pH and ionic strength was found.
      Moreover, the influence of Tween 20 over the analytical parameters was studied.
      The limits of detection of the optimised assays were below 0.1 MUg L(-1).
      Excellent recoveries, even at 10 MUg kg(-1), were obtained when strawberry,
      tomato, and cucumber samples spiked with trifloxystrobin were analysed. Finally,
      statistical agreement was found between immunoassay and reference chromatographic
      results using blind-spiked and in-field treated samples.

PMID- 24874357
TI  - Bread enriched with quinoa leaves - the influence of protein-phenolics
      interactions on the nutritional and antioxidant quality.
AB  - This paper investigates the functional and potential biological properties of
      bread fortified with quinoa leaves (QL) in the light of protein-phenolic
      interactions. The addition of QL changed the textural properties of bread crumb.
      With the replacement of wheat flour by QL (1-5%), a linear increase in crumb
      hardness, cohesiveness and gumminess was observed. Fortification positively
      affected antioxidant properties and phenolic contents; however, in some cases
      experimental values were significantly lower than those predicted. The QL
      addition affected nutrient content and digestibility. The starch digestibility of
      the bread investigated in this study was inversely proportional to the percentage
      content of QL (the changes in protein digestibility were not so pronounced).
      Increasing peak areas of extracts obtained after digestion of fortified bread and
      the significant reduction of free amino groups confirm the presence of
      interactions between phenolics and proteins. The quality of fortified bread is
      strongly affected by phenolic compounds and food matrix interactions. 

PMID- 24874358
TI  - Effect of sunlight exposure on the release of intentionally and/or non
      intentionally added substances from polyethylene terephthalate (PET) bottles into
      water: chemical analysis and in vitro toxicity.
AB  - The effect of sunlight exposure on chemical migration into PET-bottled waters was
      investigated. Bottled waters were exposed to natural sunlight for 2, 6 and 10
      days. Migration was dependent on the type of water. Formaldehyde, acetaldehyde
      and Sb migration increased with sunlight exposure in ultrapure water. In
      carbonated waters, carbon dioxide promoted migration and only formaldehyde
      increased slightly due to sunlight. Since no aldehydes were detected in non
      carbonated waters, we conclude that sunlight exposure has no effect. Concerning
      Sb, its migration levels were higher in carbonated waters. No unpredictable NIAS
      were identified in PET-bottled water extracts. Cyto-genotoxicity (Ames and
      micronucleus assays) and potential endocrine disruption effects (transcriptional
      reporter gene assays) were checked in bottled water extracts using bacteria
      (Salmonella typhimurium) and human cell lines (HepG2 and MDA-MB453-kb2). PET
      bottled water extracts did not induce any toxic effects (cyto-genotoxicity,
      estrogenic or anti-androgenic activity) in vitro at relevant consumer-exposure
      levels.

PMID- 24874359
TI  - Traceback identification of plant components in commercial compound feed through
      an oligonucleotide microarray based on tubulin intron polymorphism.
AB  - According to EU Regulations, all components of commercial compound feed need to
      be declared on the label. Effective protection against fraud requires severe
      controls based on accurate analytical methods to ascertain what is declared by
      the producers. The aim of this work was to develop an oligonucleotide microarray
      for the molecular recognition of multiple plant components in commercial feeds.
      We tested the potential of the highly polymorphic first intron sequences from
      members of the plant beta-tubulin gene family as a target for plant DNA
      identification. 23 oligonucleotide capture probes, targeting species-specific
      intron sequences, were assembled within a low density microarray for the
      identification of 10 plant species, selected from among those most commonly used
      in cattle feed formulation. The ability of the array to detect specific
      components in complex flour blends and in compound feed was evaluated. 

PMID- 24874360
TI  - Coffee with cinnamon - impact of phytochemicals interactions on antioxidant and
      anti-inflammatory in vitro activity.
AB  - This paper evaluates the potential bioaccessibility and interactions between
      antiradical and anti-inflammatory compounds from coffee and cinnamon. Results
      obtained for whole plant material extracts were compared with those for
      chlorogenic and cinnamic acids (the main bioactive constituents of the study
      material). All samples, coffee, cinnamon and a mixture of the two showed
      abilities to scavenge free radicals and to inhibit lipoxygenase (LOX) activity.
      Both activities increased after simulated gastrointestinal digestion. In the
      mixture antiradical phytochemicals acted antagonistically - isoboles adopted the
      convex form. The same interactions were determined for chemical standards. The
      water-extractable LOX inhibitors acted synergistically - the isobole curve was
      "concave". The same type of interaction was determined for standard compounds.
      Interestingly, after digestion in vitro a slight antagonism in the action of LOX
      inhibitors was observed. The results show that the food matrix and/or its changes
      during digestion may play an important role in creating the biological
      properties. 

PMID- 24874361
TI  - Biomimetic synthesis and antioxidant evaluation of 3,4-DHPEA-EDA [2-(3,4
      hydroxyphenyl) ethyl (3S,4E)-4-formyl-3-(2-oxoethyl)hex-4-enoate].
AB  - Phenolic compounds present in extra virgin olive oil have attracted considerable
      recent attention. Many of them, show specific anti-inflammatory and anti-tumor
      activities. In this work we describe the biomimetic synthesis of 3,4-DHPEA-EDA [2
      (3,4-hydroxyphenyl) ethyl (3S,4E)-4-formyl-3-(2-oxoethyl)hex-4-enoate], starting
      from natural demethyloleuropein present in olive tissues. A comparison between
      3,4-DHPEA-EDA (6) and oleuropein (1), oleuropein aglycone (4) and hydroxytyrosol
      ORACFL values was undertaken.

PMID- 24874362
TI  - A highly rapid and simple competitive enzyme-linked immunosorbent assay for
      monitoring paralytic shellfish poisoning toxins in shellfish.
AB  - Using a streptavidin-coated well plate, a biotin-labelled anti-gonyautoxin 2/3
      monoclonal antibody GT-13A, and a decarbamoyl saxitoxin-peroxidase conjugate, a
      direct competitive enzyme-linked immunosorbent assay (PSP-ELISA) was developed
      for monitoring paralytic shellfish poisoning (PSP) toxins in shellfish. This
      assay is simple to perform and can be completed in approximately 20 min. The PSP
      ELISA was compared to the mouse bioassay (MBA) for the detection of PSP toxins in
      shellfish samples (n=83) collected from the coast of Osaka Prefecture, Japan.
      When positive and negative results were indicated based on the regulatory limit
      for PSP toxins (4 mouse unit(MU)/g of shellfish meat), the PSP-ELISA results
      showed a sensitivity of 100% (25 of 25) and a specificity of 89.7% (52 of 58
      samples) compared to the MBA results. These results suggest that the PSP-ELISA
      could be used as a rapid and simple screening method prior to the MBA.

PMID- 24874363
TI  - Characterisation of the turbid particles in the extraction of sugar beet pectins.
AB  - This paper was aimed at characterising the insoluble substances (IS) responsible
      for the turbidity of the extract and impurity of the resulting pectins. Results
      showed that the IS caused a significant increase in the turbidity of the extract.
      The IS had bi-pyramidal shapes under the SEM observation. The observed XRD peaks
      for the IS were similar to those of calcium oxalate dihydrate (COD). Moreover,
      the IS consisted of mainly oxalate and calcium. Results from the present study
      indicate the IS is COD. The influence of the IS on the purity of pectin was also
      studied. The presence of the IS in the pectins indicated the IS can precipitate
      with pectins during the alcohol precipitation, thereby contaminating the
      resulting pectins.

PMID- 24874364
TI  - Vortex-assisted magnetic dispersive solid-phase microextraction for rapid
      screening and recognition of dicofol residues in tea products.
AB  - A simple and rapid vortex-assisted magnetic dispersive solid-phase
      microextraction (VAMDSME) method coupled with gas chromatography-electronic
      capture detection was developed for rapid screening and selective recognition of
      dicofol in tea products. The magnetic molecularly imprinted microspheres (mag
      MIMs) synthesised by aqueous suspension polymerisation using
      dichlorodiphenyltrichloroethane (DDT) as a dummy template showed high selectivity
      and affinity to dicofol in aqueous solution and were successfully applied as
      special adsorbents of VAMDSME for rapid isolation of dicofol from complex tea
      matrix. Good linearity was obtained in a range of 0.2-160 ng g(-1) and the limit
      of detection based on a signal to noise ratio of 3 was 0.05 ng g(-1). The
      recoveries at three spiked levels ranged from 83.6% to 94.5% with the related
      standard deviations (RSD) ? 5.0%. The VAMDSME-GC protocol, which took advantages
      of the selective adsorption of molecularly imprinted microspheres and rapid
      magnetic phase separation, as well as the short equilibrium time by vortex
      assisted, could avoid the time-consuming procedures related to other traditional
      extraction methods.

PMID- 24874365
TI  - Stability of nitrofuran residues during honey processing and nitrofuran removal
      by macroporous adsorption resins.
AB  - There is increasing concern that the presence of antibiotics such as nitrofurans
      in animal-derived food products is harmful to human. This study originally
      assessed the effects of different honey processing steps on the stabilities of
      four nitrofuran metabolites (3-amino-2-oxazolidone, 1-aminohydantonin,
      semicarbazide and 3-amino-5-morpholinomethyl-2-oxazolidone). Macroporous
      adsorption resins (MARs) were evaluated for the removal of these residues.
      Nitrofuran metabolites were analysed by LC-MS/MS after each processing step. The
      results revealed that honey processing reduced nitrofuran metabolites in honey
      and the total loss was from 56.6% to 90.4%. Furthermore, LS-901 was the optimum
      MAR with adsorption rates of 69.9-91.8% for four metabolites. After removing
      nitrofuran metabolites, the honey could be safely used as winter feed for
      honeybees.

PMID- 24874367
TI  - Volatile profile of Madeira wines submitted to traditional accelerated ageing.
AB  - The evolution of monovarietal fortified Madeira wines forced-aged by traditional
      thermal processing (estufagem) were studied in terms of volatiles. SPE extracts
      were analysed by GC-MS before and after heating at 45  degrees C for 3 months
      (standard) and at 70  degrees C for 1 month (overheating). One hundred and ninety
      volatile compounds were identified, 53 of which were only encountered in baked
      wines. Most chemical families increased after standard heating, especially furans
      and esters, up to 61 and 3-fold, respectively. On the contrary, alcohols,
      acetates and fatty acids decreased after heating. Varietal aromas, such as
      Malvasia's monoterpenic alcohols were not detected after baking. The accelerated
      ageing favoured the development of some volatiles previously reported as typical
      aromas of finest Madeira wines, particularly phenylacetaldeyde, beta-damascenone
      and 5-ethoxymethylfurfural. Additionally, ethyl butyrate, ethyl 2-methylbutyrate,
      ethyl caproate, ethyl isovalerate, guaiacol, 5-hydroxymethylfurfural and gamma
      decalactone were also found as potential contributors to the global aroma of
      baked wines.

PMID- 24874366
TI  - The information presented on labels for bread produced in Latvia.
AB  - Bakery products, particularly bread, make up a significant share of the food
      guide pyramid. To help consumers make more informed choices from the bread
      available in the market, it is essential to provide correct and appropriate
      information on food labels. The aim of this research was to analyse the
      information shown on labels for different types of bread produced in Latvia.
      Different types of bread were chosen from 28 bakeries located in regions
      throughout Latvia. For statistical analysis, the data were processed using the S
      PLUS 6.1 Professional Edition. From the analysis of labels on bread in Latvian,
      we conclude there is an absence of information about energy; only 4.8% of labels
      presented energy calculated according to the Nutritional Labelling Regulation
      90/496/ECC. 

PMID- 24874368
TI  - Enrichment and purification of marine polyphenol phlorotannins using macroporous
      adsorption resins.
AB  - Phlorotannins are one of the most important bioactive polyphenols; however, their
      purification using chromatographic methods has not been explored. Here, we
      studied purification of phlorotannins from the crude phlorotannin extract (CPhE)
      of the brown seaweed Ecklonia cava using macroporous adsorption resins. For
      purification of phlorotannins, four resins (HP-20, SP-850, XAD-7HP, and XAD-2)
      were screened. Among them, HP-20 resin showed the highest adsorption and
      desorption capacities. In static adsorption tests, the adsorption capacity of HP
      20 increased with increasing temperature (25-45 degrees C). Optimal conditions
      for the dynamic experiments can be summarized as follows: total phlorotannin
      content (TPhC) in loading solution: 1.5mg PGE/mL, processing volume: 4 BV, flow
      rate: 1 mL/min, temperature: 45 degrees C, desorption solvent: 40% ethanol
      solution. After purification, TPhC (452 mg PGE/g) and arsenic (180 MUg/g) of CPhE
      increased and decreased to 905 mg PGE/g and 48 MUg/g, respectively. Recovery rate
      of phlorotannins from CPhE was 92%.

PMID- 24874369
TI  - The freshwater alga Chroothece richteriana (Rhodophyta) as a potential source of
      lipids.
AB  - During an ecological study of Chroothece (Rhodophyta) in a small river in a semi
      arid region of south-east Spain it became clear that most of these cells had a
      high lipid content. This suggested potential uses in biotechnology, which has
      been investigated further. The colonies, which occur in full sunlight, are
      typically orange-brown. Most, perhaps all, the yellow-orange colour is associated
      with their high carotenoid content, with the carotenoid to chlorophyll ratio up
      to 2.7. The polyunsaturated fatty acyl composition of the glycerides was 35.3% of
      the dry weight. This consisted mainly of omega-3 (5.9%) and omega-6 (29.4%) fats.
      The relatively high proportion of docosahexaenoyl (1.78%), eicosapentaenoyl
      (14.15%), arachidonoyl (0.92%) and gamma-linolenoyl (0.78%) suggests use for
      medical and dietary purposes. All cells have a high phycocyanin content whilst
      phycoerythrin is absent. The alga has a wide distribution globally and hence
      provides scope for selecting strains with optimum properties. 

PMID- 24874370
TI  - Development of novel nano-biocomposite antioxidant films based on poly (lactic
      acid) and thymol for active packaging.
AB  - Novel nano-biocomposite films based on poly (lactic acid) (PLA) were prepared by
      incorporating thymol, as the active additive, and modified montmorillonite (D43B)
      at two different concentrations. A complete thermal, structural, mechanical and
      functional characterization of all nano-biocomposites was carried out. Thermal
      stability was not significantly affected by the addition of thymol, but the
      incorporation of D43B improved mechanical properties and reduced the oxygen
      transmission rate by the formation of intercalated structures, as suggested by
      wide angle X-ray scattering patterns and transmission electron microscopy images.
      The addition of thymol decreased the PLA glass transition temperature, as the
      result of the polymer plasticization, and led to modification of the elastic
      modulus and elongation at break. Finally, the amount of thymol remaining in these
      formulations was determined by liquid chromatography (HPLC-UV) and the
      antioxidant activity by the DPPH spectroscopic method, suggesting that the
      formulated nano-biocomposites could be considered a promising antioxidant active
      packaging material. 

PMID- 24874371
TI  - Quality enhancement in the Japanese sea bass (Lateolabrax japonicas) fillets
      stored at 4 degrees C by chitosan coating incorporated with citric acid or
      licorice extract.
AB  - The preserving effects of chitosan, chitosan and citric acid, chitosan and
      licorice extract on fresh Japanese sea bass fillets stored at 4  degrees C for 12
      days were studied. Results showed that citric acid or licorice extract can
      enhance the preserving function of chitosan significantly by retarding lipid
      oxidation and inhibiting microbial growth as reflected in thiobarbituric acid
      reactive substances and total plate count, respectively. Both total volatile
      basic nitrogen values and sensory scores indicated chitosan and citric acid or
      licorice extract can significantly reduce the quality loss and extend the shelf
      life of Japanese sea bass fish fillets during refrigerated storage. Citric acid
      or licorice extract with chitosan could thus be applied in the seafood industry
      to enhance quality of fish fillets as natural preservatives.

PMID- 24874372
TI  - Olive oil phenolic compounds decrease the postprandial inflammatory response by
      reducing postprandial plasma lipopolysaccharide levels.
AB  - We investigated the molecular mechanisms by which phenolic compounds (phenols) in
      virgin olive oil reduce the postprandial inflammatory response with the aim of
      identifying the transcription factor involved and the downstream effects. Olive
      oil-based breakfasts prepared with virgin olive oil (VOO) with high (398 ppm),
      intermediate (149 ppm) and low (70 ppm) phenol content were administered to 49
      metabolic syndrome patients following a randomized crossover design. The
      consumption of a high-phenol VOO-based breakfast limited the increase of
      lipopolysaccharide plasma levels, TLR4, and SOCS3 proteins (p<0.001, p=0.041 and
      p=0.008, respectively), the activation of NF-kappaB (p=0.016) and the IL6
      (p=0.007 and p=0.048, low and intermediate oil, respectively), IL1B (p=0.002,
      intermediate oil), and CXCL1 (p=0.001) postprandial gene expression, in
      peripheral blood mononuclear cells, as compared with the consumption of a
      breakfast prepared with the same oil but with low or intermediate phenol content.
      Virgin olive oil phenolic compounds reduce the postprandial inflammatory response
      in association with postprandial plasma lipopolysaccharide levels.

PMID- 24874373
TI  - Ultra-performance convergence chromatography (UPC2) method for the analysis of
      biogenic amines in fermented foods.
AB  - A rapid ultra-performance convergence chromatography (UPC(2)) method for the
      determination of eight biogenic amines (spermine, spermidine, putrescine,
      cadaverine, tryptamine, phenylethylamine, histamine and tyramine) in fermented
      foods was developed. The amines were pre-column derivatized with dansyl chloride
      and separated on UPC(2) system with a HSS C18 SB column (3.0 * 100 mm, 1.8 MUm)
      using gradient elution with a binary system of CO2 and n
      hexane:isopropanol:ammonium hydroxide (70:30:0.15, v/v/v), back pressure of 2,000
      psi, flow rate of 2.0 ml/min and DAD detection at 254 nm. The result showed
      excellent linearity (r=0.9995-1.0000). Limits of detection (LOD) and limits of
      quantification (LOQ) were 21-67 ng/L and 72-224 ng/L, respectively. Relative
      standard deviations (RSD) for repeatability and reproducibility were 0.21-0.87%
      and 1.98-4.02%, respectively. Furthermore, this method was successfully applied
      to analysis of biogenic amines in Yulu and Sufu samples.

PMID- 24874374
TI  - Thermal degradation of cloudy apple juice phenolic constituents.
AB  - Although conventional thermal processing is still the most commonly used
      preservation technique in cloudy apple juice production, detailed knowledge on
      phenolic compound degradation during thermal treatment is still limited. To
      evaluate the extent of thermal degradation as a function of time and temperature,
      apple juice samples were isothermally treated during 7,200s over a temperature
      range of 80-145  degrees C. An untargeted metabolomics approach based on liquid
      chromatography-high resolution mass spectrometry was developed and applied with
      the aim to find out the most heat labile phenolic constituents in cloudy apple
      juice. By the use of a high resolution mass spectrometer, the high degree of in
      source fragmentation, the quality of deconvolution and the employed custom-made
      database, it was possible to achieve a high degree of structural elucidation for
      the thermolabile phenolic constituents. Procyanidin subclass representatives were
      discovered as the most heat labile phenolic compounds of cloudy apple juice.

PMID- 24874375
TI  - Chemical guide parameters for Spanish lemon (Citrus limon (L.) Burm.) juices.
AB  - To contribute for setting reference guideline for commercial juice extracted from
      the Spanish lemon varieties, chemical composition of 92 direct and 92
      reconstituted samples were investigated. In direct lemon juice, titratable
      acidity was 52.4 g/L, being the citric acid the main component. Glucose, fructose
      and sucrose concentrations were 7.9, 7.3 and 4.5 g/L, respectively. Predominant
      mineral was potassium (1264.2mg/L), followed by phosphorous (306 mg/L), calcium
      (112 mg/L) and magnesium (92.6 mg/L). Hesperidin ranged from 257 to 484.8 mg/L,
      while water soluble pectins varied between 164.8 and 550 mg/L. Similar values
      were obtained in reconstituted lemon juice. There are different parameters that
      did not reach or exceeded the limits proposed by the European Association of the
      Industry of Juices and Nectars. These levels should be taken into account to
      modify the present reference guideline and that Spanish lemon juices are not
      discarded for to have lower or bigger values.

PMID- 24874376
TI  - The application of chitosan and benzothiadiazole in vineyard (Vitis vinifera L.
      cv Groppello Gentile) changes the aromatic profile and sensory attributes of
      wine.
AB  - This work reports the effects of resistance inducers on wine aroma compounds and
      sensory attributes. Resistance inducers are a class of products able to elicit
      the plant defence mechanisms against pathogens, incurring lower toxicological
      risks than conventional agrochemicals. Among them, chitosan (CHT) and
      benzothiadiazole (BTH) are particularly effective in stimulating the biosynthesis
      of bioactive phytochemicals. They were used in a two-year survey conducted to
      assess experimental wines obtained from elicitor-treated grapes. Compared with
      conventional fungicides (penconazole and methyldinocap), in 2009, BTH increased
      total acetals and esters, while CHT raised the levels of total acetals and
      alcohols. Sensory analysis revealed that overall acceptance was higher in CHT
      than in BTH. In 2010, differences were not significant. Therefore, plant
      activators deserve attention beyond their efficacy in crop protection. In
      particular, in our experimental conditions, CHT improved the volatile profile,
      flavour and taste of Groppello wine.

PMID- 24874377
TI  - Genotoxicity of processed food items and ready-to-eat snacks in Finland.
AB  - Processed foods are an insufficiently characterized source of chemical mutagens
      for consumers. Here, we evaluated the genotoxicity of selected food products in
      Finland. Mutagenicity was determined by the standard plate incorporation assay
      followed by methylcellulose overlay and treat-and-wash assays, using the
      Salmonella strains TA 100 and 98 with and without metabolic activation.
      Generally, the mutagenic activity of food samples was low, but exhibited lot-wise
      variation. Cold cuts of cold-smoked beef, grilled turkey, and smoked chicken (a
      single batch of each) were mutagenic in all three assays with the TA 100 strain
      with and without metabolic activation, indicating the mutagenic effect was not
      secondary to histidine release from the food products. However, none of the food
      extracts showing mutagenic potential induced DNA damage in vitro using the Comet
      Assay. Our findings imply that in Finland today, there are still products the
      production methods of which should be refined to reduce the potential risk of
      mutagenicity to consumers. 

PMID- 24874378
TI  - Cherry tomatoes metabolic profile determined by 1H-High Resolution-NMR
      spectroscopy as influenced by growing season.
AB  - The content of the most valuable metabolites present in the lipophilic fraction
      of Protected Geographical Indication cherry tomatoes produced in Pachino (Italy)
      was observed for 2 cultivated varieties, i.e. cv. Naomi and cv. Shiren, over a
      period of 3 years in order to observe variations due to relevant climatic
      parameters, e.g. solar radiation and average temperature, characterising
      different seasons. (1)H-NMR spectroscopy was applied and spectral data were
      processed by means of Principal Component Analysis (PCA). We found that the
      metabolic profile was different for the two considered cultivated varieties and
      they were differently affected by climatic conditions. Major metabolites
      influenced by cropping period were alpha-tocopherol and the unsaturated lipid
      fraction in Naomi cherry tomatoes, and chlorophylls and phospholipids in Shiren
      variety, respectively. These results furnished useful information on seasonal
      dynamics of such important nutritional metabolites contained in tomatoes,
      confirming also NMR spectroscopy as powerful tool to define a complete metabolic
      profiling.

PMID- 24874379
TI  - Green preparation and characterisation of waxy maize starch nanoparticles through
      enzymolysis and recrystallisation.
AB  - Waxy maize starch was treated by a facile and green enzymolysis procedure to
      fabricate starch nanoparticles (StNPs). The yield of StNPs was raised to 85% by
      pullulanase treatment, and the preparation duration was two days. Morphology
      (SEM, TEM), crystalline structure (XRD), thermal gravimetry analysis (TGA), and
      the group changing (FTIR) of StNPs prepared with different starch concentrations
      (10%, 15%, 20% and 25%,w/v) were investigated. Compared with native starch, the
      topography of all StNPs exhibited irregularly-shaped fragments, the particle
      diameters decreased from several MUm to about 60-120 nm, and the crystal pattern
      changed from A-type to B+V-type. The StNPs prepared with 15% starch slurry had
      the highest degree of crystallinity at 55.41%. The eco-friendly prepared
      nanoparticles could be widely used in biomedical applications and development of
      new materials.

PMID- 24874380
TI  - A novel low-temperature-active pectin methylesterase from Penicillium chrysogenum
      F46 with high efficiency in fruit firming.
AB  - A pectin methylesterase gene (pe8F46) was cloned from Penicillium chrysogenum F46
      and successfully expressed in Pichia pastoris. The full-length cDNA consists of
      969 bp and encodes a 322-residue polypeptide with the calculated molecular weight
      of 34.1 kDa. Deduced PE8F46 belongs to family 8 of carbohydrate esterases and
      shares 54% identity with a functionally characterised counterpart from
      Myceliophthora thermophile. Purified recombinant PE8F46 showed the optimal
      activity at pH 5.0 and 40 degrees C, and remained 52% maximum activity even at 10
      degrees C. An orthogonal experiment was employed to determine the best conditions
      for firming pineapple dices. After incubation with 0.75% (w/v) PE8F46 and 0.4%
      calcium lactate (w/v) for 20 min, the firmness of pineapple dices was improved by
      47.6%, 13.7% higher than that of a commercial pectinase complex. These results
      suggest that PE8F46 has application potential in the food industry.

PMID- 24874381
TI  - High-throughput analysis of lipid hydroperoxides in edible oils and fats using
      the fluorescent reagent diphenyl-1-pyrenylphosphine.
AB  - A fluorometric method for the determination of hydroperoxides (HP) in edible oils
      and fats using the reagent diphenyl-1-pyrenylphosphine (DPPP) was developed and
      validated. Two solvent media containing 100% butanol or a mixture of
      chloroform/methanol (2:1, v/v) can be used to solubilise lipid samples.
      Regardless of the solvent used to solubilise the sample, the DPPP method was
      precise, accurate, sensitive and easy to perform. The HP content of 43 oil and
      fat samples was determined and the results were compared with those obtained by
      means of the AOCS Official Method for the determination of peroxide value (PV)
      and the ferrous oxidation-xylenol orange (FOX) method. The proposed method not
      only correlates well with the PV and FOX methods, but also presents some
      advantages such as requiring low sample and solvent amounts and being suitable
      for high-throughput sample analysis. 

PMID- 24874382
TI  - Determination of flumioxazin residue in food samples through a sensitive
      fluorescent sensor based on click chemistry.
AB  - A sensitive and selective fluorescent sensor for flumioxazin was designed based
      on the formation of strong fluorescence compound (1,2,3-triazole compounds) via
      the reaction of the alkynyl group in flumioxazin with 3-azido-7-hydroxycoumarin,
      a weak-fluorescent compound, through the Cu(+)-catalysed azide-alkyne
      cycloaddition (CuAAC) reaction. The fluorescence increase factor (represented by
      F/F0) of the system exhibited a good linear relationship with the concentrations
      of flumioxazin in the range of 0.25-6.0 MUg/L with a detection limit of 0.18
      MUg/L (S/N=3). Also, the proposed fluorescent sensor demonstrated good
      selectivity for flumioxazin assay even in the presence of high concentration of
      other pesticides. Based on such high sensitivity and selectivity, the proposed
      fluorescent sensor has been applied to test the flumioxazin residue in some
      vegetable and water samples with satisfied results.

PMID- 24874383
TI  - Lipophilic phytochemicals from banana fruits of several Musa species.
AB  - The chemical composition of the lipophilic extract of ripe pulp of banana fruit
      from several banana cultivars belonging to the Musa acuminata and Musa balbisiana
      species (namely 'Chinese Cavendish', 'Giant Cavendish', 'Dwarf Red', 'Grand
      Nain', 'Eilon', 'Gruesa', 'Silver', 'Ricasa', 'Williams' and 'Zelig') was studied
      by gas chromatography-mass spectrometry for the first time. The banana cultivars
      showed similar amounts of lipophilic extractives (ca. 0.4% of dry material
      weight) as well as qualitative chemical compositions. The major groups of
      compounds identified in these fractions were fatty acids and sterols making up
      68.6-84.3% and 11.1-28.0%, respectively, of the total amount of lipophilic
      components. Smaller amounts of long chain aliphatic alcohols and alpha-tocopherol
      were also identified. These results are a relevant contribution for the
      valorisation of these banana cultivars as sources of valuable phytochemicals
      (omega-3 and omega-6 fatty acids, and sterols) with well-established beneficial
      nutritional and health effects. 

PMID- 24874384
TI  - Medium-assisted non-polar solvent dynamic microwave extraction for determination
      of organophosphorus pesticides in cereals using gas chromatography-mass
      spectrometry.
AB  - A fast and green pretreatment method, medium-assisted non-polar solvent dynamic
      microwave extraction, was first applied to extract ten of organophosphorus
      pesticides (OPPs) from five cereal samples. Without adding any polar solvent,
      graphite powders (GP) were used as microwave absorption medium to transform
      microwave energy into heat energy. For recycling GP, an extractor was made by
      sealing GP inside the exterior tube of a glass sleeve. By dynamic microwave
      extraction using hexane as extraction solvent, ten OPPs could be extracted
      completely within 200s, and the extract was directly analysed by GC-MS without
      any clean-up process. The effects of some experimental parameters on extraction
      efficiency were investigated and optimised. Relative standard deviations of intra
      and inter-day ranging from 1.02% to 5.32% were obtained. Five real samples were
      analysed, and the recoveries obtained were in the range of 73.2-99.8%, and the
      relative standard deviations were lower than 6.63%.

PMID- 24874385
TI  - Microwave-assisted deuterium exchange: the convenient preparation of isotopically
      labelled analogues for stable isotope dilution analysis of volatile wine phenols.
AB  - This study reports the convenient, low cost, one-step synthesis of labelled
      analogues of six volatile phenols, guaiacol, 4-methylguaiacol, 4-ethylguaiacol, 4
      ethylphenol, eugenol and vanillin, using microwave-assisted deuterium exchange,
      for use as internal standards for stable isotope dilution analysis. The current
      method improves on previous strategies in that it enables incorporation of
      deuterium atoms on the aromatic ring, thereby ensuring retention of the isotope
      label during mass spectrometry fragmentation. When used as standards for SIDA,
      these labelled volatile phenols will improve the accuracy and reproducibility of
      quantitative food and beverage analysis.

PMID- 24874386
TI  - Effects of low frequency ultrasonic treatment on the maturation of steeped
      greengage wine.
AB  - To accelerate wine maturation, low frequency ultrasonic waves of 28 kHz and 45
      kHz were used to treat the steeped greengage wine. The contents of total acid,
      total ester, fusel oils and the wine chromaticity were determined before and
      after the ultrasonic treatment. The volatile compounds were analysed by GC-MS
      method, and the sensory quality was evaluated by panelist. The results indicated
      that ultrasonic treatment of the steeped greengage wine at 45 kHz 360 W for 30
      min was effective to accelerate the aging process, where the fusel oils and
      alcohol compounds were significantly reduced and acid and ester compounds were
      significantly increased.

PMID- 24874387
TI  - Gas chromatography with flame photometric detection of 31 organophosphorus
      pesticide residues in Alpinia oxyphylla dried fruits.
AB  - A simple, rapid and effective gas chromatography-flame photometric detection
      method was established for simultaneous multi-component determination of 31
      organophosphorus pesticides (OPPs) residues in Alpinia oxyphylla, which is widely
      consumed as a traditional medicine and food in China. Sample preparation was
      completed in a single step without any clean-up procedure. All pesticides
      expressed good linear relationships between 0.004 and 1.0 MUg/mL with correlation
      coefficients higher than 0.9973. The method gave satisfactory recoveries for most
      pesticides. The limits of detection varied from 1 to 10 ng/mL, and the limits of
      quantification (LOQs) were between 4 and 30 ng/mL. The proposed method was
      successfully applied to 55 commercial samples purchased from five different
      areas. Five pesticide residues were detected in four (7.27%) samples. The
      positive samples were confirmed by gas chromatography with tandem mass
      spectrometry (GC-MS/MS).

PMID- 24874388
TI  - Deployment of response surface methodology to optimize recovery of dark fresh fig
      (Ficus carica L., var. Azenjar) total phenolic compounds and antioxidant
      activity.
AB  - Optimum conditions for extracting total phenolic compounds (TPC) and antioxidant
      activity from fresh dark fig (Ficus carica L.) have been investigated using
      response surface methodology (RSM). The Box-Behnken design was used to
      investigate the effects of three independent variables, acetone concentration (40
      80%), temperature (25-65  degrees C), and time (60-120 min), on the response.
      Regression analysis showed that about 96% of the variation was explained by the
      models. P-value for the lack of fit was insignificant which confirmed the
      validity of models. Response surface analysis showed that the optimal extraction
      parameters that maximized antioxidants extraction were 63.48% acetone, 115.14
      min, and 48.66  degrees C. Under optimum conditions the corresponding
      experimental values for TPC and antioxidant activity were 536.43 and 71.86 mg
      GAE/100 g DM. The experimental values are in accordance with those predicted,
      indicating the suitability of the model and the success of RSM in optimizing the
      extraction conditions.

PMID- 24874389
TI  - Editorial.

PMID- 24874390
TI  - Scientific survey.

PMID- 24874391
TI  - Ultrastructural cytochemistry of monoamines in cultured human fetal sympathetic
      neurons.
AB  - The presence and storage of adrenergic neurotransmitter (monoamines) in cultured
      human fetal sympathetic neurons was investigated by chromate-dichromate
      cytochemistry, formaldehyde-induced fluorescence and potassium permanganate
      fixation. Monoamines were specifically identified in the neurons by the presence
      of an electron dense precipitate following cytochemical treatment. Reaction
      product was found in cell somas and processes in all chromate-dichromate treated
      cultures. The size range and morphology of the precipitate indicated a vesicular
      storage site within large dense core vesicles. Neurons fluoresced after treatment
      with formaldehyde vapors, further confirming the presence of monoamines. When
      potassium permanganate was employed as the fixative, occasional positive dense
      core vesicles were found but their frequency was greatly reduced from that seen
      in the chromate-dichromate treated cultures. These findings show that cultured
      human fetal sympathetic neurons retain an adrenergic phenotype during long-term
      serum-free culture. In addition, the storage site for the adrenergic
      neurotransmitter in the developing neuron is within large dense core vesicles.
      The lack of dense core vesicles in potassium permanganate fixed material is
      believed to be due to the depletion of monoamines during fixation. 

PMID- 24874392
TI  - A chick neural antigen identified by monoclonal antibodies.
AB  - A monoclonal antibody technique has been used to locate a neural antigen which
      appears to be involved in developmental processes. Hybridomas were prepared using
      chick embryo sympathetic neurons as an immunogen and one clone, H3, was found to
      secrete antibodies which bound to neurons of the peripheral and central nervous
      system. The antibodies bound to both membrane and cytoplasmic sites of neurons
      but only to cytoplasmic sites of glial cells. When added to newly prepared
      cultures of embryonic sympathetic neurons the H3 antibodies impaired both neurite
      outgrowth and long-term neuronal viability. No such effect was seen when the
      antibodies were added to established, differentiated neurons. 

PMID- 24874393
TI  - Modification of taurine and hypotaurine uptake systems in cultured primary
      astrocytes by serum-free medium and dibutyryl cyclic AMP treatment.
AB  - The characteristics of taurine and hypotaurine uptake were studied during
      astrocyte maturation in cultures grown in normal, serum-containing medium or in
      serum-free medium in the presence of 0.1 mmol/l dibutyryl cyclic AMP (dBcAMP).
      The uptake of both amino acids consisted of one saturable high-affinity component
      in both control and treated cultures. The dBcAMP treatment produced no marked
      modification of the transport systems. In the treated cultures the kinetic
      parameters of taurine and hypotaurine uptake remained unaltered during
      maturation. In the control cells the transport constant and maximal velocity of
      taurine uptake were greater in 21-day-old than in 16-day-old cultures, while the
      changes in hypotaurine transport were the opposite. The uptakes were strictly
      sodium-dependent and also considerably decreased when potassium ions were omitted
      from incubation medium. The uptake of both amino acids was affected more by
      potassium omission in the dBcAMP-treated than in the control cultures. Also the
      results with metabolic poisons suggest that physiological ion gradients sustained
      by an active Na(+), K(+)-pump are essential for the normal uptake of taurine and
      hypotaurine. 

PMID- 24874394
TI  - Cell death during development of the cochlear and vestibular ganglia of the
      chick.
AB  - This report documents and quantitates the naturally occurring death of neurons in
      the cochlear and vestibular ganglia during the normal development of the chick
      embryo. The data are compared with the amount of cell loss in the cochlear and
      vestibular nuclei to evaluate the possibility that the death of the neurons in
      the same sensory pathway may be related to the formation of their connections.
      Neurons of the cochlear and vestibular ganglia of the chick were counted and
      their cell bodies measured with light microscopic methods at the beginning of
      their period of synapse formation, embryonic day 8 (E8), at the end of the period
      of synapse formation (E14), and again at a more mature stage, post-hatching day
      14 (P14). The number of neurons declined between E8 and E14 in the cochlear
      ganglion by 25% (from 11170 to 8353) and in the vestibular ganglion by 24% (from
      12687 to 9613). The neuronal population remained relatively stable between E14
      and P14. Cell counts at each age were accompanied by morphological descriptions
      of the neurons and of their synaptic targets in the sensory epithelia of the
      inner ear. During the period of cell loss the mean diameters of the cell bodies
      in the cochlear ganglion increased slightly, from 9.5 to 111 MUm and reached 17.6
      MUm at P14, while those in the vestibular ganglion increased from 10.4 to 13.3
      MUm and reached 20.9 MUm at P14. The period of cell loss in the cochlear and
      vestibular ganglia coincides with the stages in their development when the
      sensory neurons have already contacted their target cells in the primary sensory
      nuclei and in the receptor epithelium. It is during this period that the
      transformation from the immature axonal endings to the definitive types of
      synapses begins. Thus the present data are consistent with the view that the
      formation of central as well as peripheral synapses is involved in determining
      the extent of neuronal death during the development of sensory neurons. 

PMID- 24874395
TI  - Comparison of embryonic and adult torpedo acetylcholine receptor by sedimentation
      characteristics and antigenicity.
AB  - The acetylcholine receptor (AChR) from Torpedo marmorata electric organ exists in
      a light form (alpha2betagammadelta) of apparent molecular weight 250,000. The
      association of two light forms via an intermolecular delta-delta disulfide bridge
      results in the AChR heavy form. In adult Torpedo electric organ extracts the
      heavy form constitutes about 70% of the AChR. We report that, in contrast,
      embryonic electric organ extracts contain only about 30% of the heavy form, the
      rest being light form. In addition, amongst a library of 38 monoclonal antibodies
      (mAbs), all of those that distinguished between embryonic and adult AChR did so
      only because they precipitated the heavy form of the AChR better than the light
      form. 

PMID- 24874396
TI  - Effect of hydrocortisone on the number of small intensely fluorescent cells in
      the rat superior cervical ganglion during pre- and postnatal development.
AB  - During the first postnatal week hydrocortisone causes a massive increase in the
      number of small intensely fluorescent (SIF) cells. The purpose of the present
      study was to investigate whether the number of SIF cells can be increased with
      hydrocortisone also prenatally and after the first postnatal week. Because it was
      desirable to apply the same kind of treatment before and after birth, the embryos
      and neonatal rats were injected only once and were studied 4 days later. Pregnant
      rats were injected daily during the last 7 days of pregnancy and the superior
      cervical ganglia of their embryos were studied thereafter. After birth, the
      effect of 7 daily injections of hydrocortisone was also studied. The number of
      embryonal brightly fluorescent cells, the probable prenatal precursors of the SIF
      cells. could not be increased either with a single injection into the embryos, or
      in embryos of pregnant rats treated with hydrocortisone. A single injection of
      hydrocortisone into newborn and 4-day-old rats caused a massive increase in the
      number of SIF cells as studied in 4- and 8-day-old rats, respectively. The
      increase in the number of SIF cells was smaller but still statistically
      significant in 12-day-old rats injected with hydrocortisone on postnatal day 8.
      Daily injections of hydrocortisone for 7 days caused on the second, but not on
      the third postnatal week, a statistically significant increase in the number of
      SIF cells. After 7 injections of hydrocortisone. on postnatal days 3-9 or 40-46.
      no increase in the number of SIF cells was observed in 47-day-old rats, as
      compared with saline-treated controls of the same age, but 7 injections of
      hydrocortisone both on days 3-9 and 40-46 resulted in a significant increase in
      the number of small intensely fluorescent cells on day 47. It is concluded that
      hydrocortisone-induced increase in the number of SIF cells is limited in vivo to
      the first two postnatal weeks, while exposure to hydrocortisone at birth restores
      the responsiveness of these cells to increase in number even later after a second
      exposure to hydrocortisone. 

PMID- 24874397
TI  - Breeding rats on amino acid imbalanced diets for three consecutive generations
      affects the concentrations of putative amino acid transmitters in the developing
      brain.
AB  - Rats were bred for three consecutive generations (F1, F2, F3) on different amino
      acid enriched diets (tryptophan-enriched, phenylalanine-enriched, tyrosine
      enriched, valine-isoleucineleucine-enriched). The concentrations of the putative
      amino acid transmitters glycine, glutamate, aspartate, gamma-aminobutyric acid,
      and taurine were measured in the brain stem of the developing offsprings by thin
      layer micro-chromatography of the dansylated amino acids. The concentrations of
      the investigated amino acid transmitters in the brain stem of the developing
      offspring of the amino acid imbalanced rats differed significantly from the
      values found in normal rats. The alterations from the normal developmental
      profiles were most pronounced in the rats bred on the valine-isoleucine-leucine
      enriched diet. Also the growth rate of the developing brain in each generation
      was affected by the different dietary amino acid supply. In the third generation
      at 20 days of age, with the exception of the rats bred on the tyrosineenriched
      diets, brain weights were generally decreased. 

PMID- 24874398
TI  - Factors influencing astrocyte growth and development in defined media.
AB  - A previously described serum-free, defined medium (G2 medium) containing
      transferrin, selenium, hydrocortisone, biotin, fibroblast growth factor (FGF) and
      fibronectin developed for the growth of human and rat derived glioma cells was
      investigated for its ability to support proliferation of astrocytes in primary
      cultures of neonatal rat cerebrum. These cells were able to grow in G2 medium.
      Enhanced proliferation and repeated subcultivation were obtained after adding
      insulin and/or epidermal growth factor (EGF) to the G2 medium at concentrations
      of 5 MUg/ml and 10 ng/ml, respectively. In these modified media (called G4 and G5
      medium) astrocytes showed a higher degree of morphological differentiation as
      compared to serum supplemented medium. Cell type specificity was determined by
      immunocytochemical staining of glial fibrillary acidic (GFA) protein, which could
      already be demonstrated 5 days after plating cells. G4 and G5 represent the first
      serum-free defined media in which astrocytes proliferate and differentiate
      without preceding or intermediate contact to serum supplemented medium.
      Modification of the culture substratum by adding hyaluronic acid and chondroitin
      sulfate A to G4 medium (G2 medium + insulin) enhanced proliferation of astroglial
      cells by a factor of about 1.5. In the presence of epidermal growth factor no
      response to the altered culture dish surface was observed and the addition of
      fibronectin, otherwise a stringent plating requirement, was no longer necessary. 

PMID- 24874399
TI  - Effect of paradoxical sleep deprivation on dna synthesis in fetal rat brain.
AB  - We have investigated the effect of PS-D induced in gestating rats by treatment
      with clomipramine or with the platform technique on the process of DNA synthesis
      taking place in fetal organs. This parameter was taken as a biochemical index of
      ongoing cellular proliferation. In brain and, to a minor extent, in liver and
      kidney the rate of fetal DNA synthesis was markedly increased in both
      experimental groups. The effect was more prominent in the clomipramine group. PS
      D treatment of gestating rats, notably by the platform technique, left long
      lasting effects in the offspring with regard to organ weight and DNA
      concentration as well as to learning capacity. It is concluded that the
      occurrence of PS in gestating rats may exert a significant influence on fetal
      development. 

PMID- 24874400
TI  - Growth of myenteric plexus explant cultures in a serum-free, hormone-supplemented
      culture medium.
AB  - Explant cultures of the myenteric plexus from beneath the taenia coli of newborn
      guinea-pig caeca were grown on glass substrates in a serum-free, hormone
      supplemented culture medium. The growth of enteric neurons, glial cells and
      fibroblasts and their interactions in this medium were studied over 3 weeks in
      vitro, and compared with those of cells cultured in the presence of foetal calf
      serum and in serum-free medium in the absence of added hormones. Enteric neurons,
      glial cells and fibroblasts survived in the serum-free, hormone-supplemented
      medium, but this was dependent on the presence of the hormone supplements and
      also on a brief initial period of exposure to serum-supplemented medium. The
      pattern of development of the cultures grown in serum-free medium, however,
      differed markedly from that of cultures grown in serum-supplemented medium: the
      numbers of enteric glial cells and fibroblasts were substantially reduced in the
      absence of serum; neurites grew extensively on the glass substrate rather than
      being restricted to a carpet of glial cells; and reaggregation of neurons and
      glial cells into compact groups resembling differentiated enteric ganglia did not
      occur. This ability to grow enteric neurons in a defined chemical environment,
      without the presence of unknown serum components, thus offers an opportunity for
      detailed study of the effects of growth and trophic factors on neuronal survival,
      neurite outgrowth and neurochemical differentiation in the entericnervous system,
      and also for study of the factors involved in enteric ganglion formation. 

PMID- 24874401
TI  - Safety and efficacy assessment of two new leprosy skin test antigens: randomized
      double blind clinical study.
AB  - BACKGROUND: New tools are required for the diagnosis of pre-symptomatic leprosy
      towards further reduction of disease burden and its associated reactions. To
      address this need, two new skin test antigens were developed to assess safety and
      efficacy in human trials. METHODS: A Phase I safety trial was first conducted in
      a non-endemic region for leprosy (U.S.A.). Healthy non-exposed subjects (n = 10)
      received three titrated doses (2.5 ug, 1.0 ug and 0.1 ug) of MLSA-LAM (n = 5) or
      MLCwA (n = 5) and control antigens [Rees MLSA (1.0 ug) and saline]. A randomized
      double blind Phase II safety and efficacy trial followed in an endemic region for
      leprosy (Nepal), but involved only the 1.0 ug (high dose) and 0.1 ug (low dose)
      of each antigen; Tuberculin PPD served as a control antigen. This Phase II safety
      and efficacy trial consisted of three Stages: Stage A and B studies were an
      expansion of Phase I involving 10 and 90 subjects respectively, and Stage C was
      then conducted in two parts (high dose and low dose), each enrolling 80
      participants: 20 borderline lepromatous/lepromatous (BL/LL) leprosy patients, 20
      borderline tuberculoid/tuberculoid (BT/TT) leprosy patients, 20 household
      contacts of leprosy patients (HC), and 20 tuberculosis (TB) patients. The primary
      outcome measure for the skin test was delayed type hypersensitivity induration.
      FINDINGS: In the small Phase I safety trial, reactions were primarily against the
      2.5 ug dose of both antigens and Rees control antigen, which were then excluded
      from subsequent studies. In the Phase II, Stage A/B ramped-up safety study, 26%
      of subjects (13 of 50) showed induration against the high dose of each antigen,
      and 4% (2 of 50) reacted to the low dose of MLSA-LAM. Phase II, Stage C safety
      and initial efficacy trial showed that both antigens at the low dose exhibited
      low sensitivity at 20% and 25% in BT/TT leprosy patients, but high specificity at
      100% and 95% compared to TB patients. The high dose of both antigens showed lower
      specificity (70% and 60%) and sensitivity (10% and 15%). BL/LL leprosy patients
      were anergic to the leprosy antigens. INTERPRETATION: MLSA-LAM and MLCwA at both
      high (1.0 ug) and low (0.1 ug) doses were found to be safe for use in humans
      without known exposure to leprosy and in target populations. At a sensitivity
      rate of 20-25% these antigens are not suitable as a skin test for the detection
      of the early stages of leprosy infection; however, the degree of specificity is
      impressive given the presence of cross-reactive antigens in these complex native
      M. leprae preparations. TRIAL REGISTRATION: ClinicalTrials.gov NCT01920750 (Phase
      I), NCT00128193 (Phase II).

PMID- 24874402
TI  - [Diagnosis delay of pleural and pulmonary tuberculosis].
AB  - Tuberculosis (TB) is still being endemic in our country. Time until management
      determines both evolution and prognosis of this condition. The aim of this work
      is to evaluate the delay in diagnosis of TB in a respiratory unit from a
      university hospital series. The authors conducted a cross-sectional study
      including patients with pulmonary TBC and/or pleural. An evaluation of time
      management was conducted from the beginning of symptoms and various consultations
      with reference to the date of hospitalization and treatment set up. One hundred
      patients were included (pulmonary TB: 68 cases, pleural TB 23 cases, miliary
      pulmonary TB: 4 cases, pulmonary TB associated with other extrathoracic
      locations: 5 cases). The mean time of patient delay and total delay institution
      were respectively 43.6, 25.7 and 69.3 days. Variables responsible for long delays
      were: number of consultations more than 3 before hospitalization, empirical
      antibiotic therapy, of a regional hospital first consultation and the presence of
      extra-respiratory impairment. The patient delay was considered long. A
      reorganization of the TB control program, in particular by partial
      decentralization of care and health education is imperative in order to improve
      the quality of tuberculosis management in our country.

PMID- 24874404
TI  - [Severe community-acquired pneumonia admitted at the intensive care unit: main
      clinical and bacteriological features and prognostic factors: a Tunisian
      experience].
AB  - INTRODUCTION: Severe community-acquired pneumonia (SCAP) remains a major cause of
      death. The aim of this study was to describe the main clinical and
      bacteriological features and to determine predictive factors for death in
      patients with SCAP who were admitted in intensive care unit (ICU) in a Tunisian
      setting. METHOD: It is a retrospective study conducted between March 2005 and
      December 2010 at the intensive care unit of the University Hospital of Mahdia
      (Tunisia). All patients hospitalized at the ICU with a SCAP diagnosis according
      to the American Thoracic Society criteria were included. RESULTS: Two hundred and
      nine patients (mean age: 64+/-16 years, and mean SAPS II: 42+/-17) were included.
      Overall, 24% had a bacteriological diagnosis. Streptococcus pneumoniae was the
      most frequently detected. Use of mechanical ventilation was required in 57% of
      patients and 45% experimented septic shock upon admission. The mortality rate at
      ICU was 29% (n=60). In multivariate analysis, a septic shock at admission and the
      use of mechanical ventilation were both associated with death. CONCLUSION: SCAP
      were associated with high mortality in the ICU.

PMID- 24874403
TI  - [The role of imaging in thoracic tuberculosis].
AB  - Tuberculosis is an infectious disease mostly due to Mycobacterium tuberculosis.
      It is frequent in developing countries and its incidence is rising in developed
      countries. Lungs are the most involved organs of the chest but other structures
      can be affected. Imaging is fundamental in the management of the disease.
      Confirmation of diagnosis can be made only by bacteriologic and/or histologic
      exams. The first approach of diagnosis is based on clinical symptoms and chest X
      ray signs. Radiologic signs depend on patient's age, his immune status and his
      previous contact with M. tuberculosis. Conventional chest X-ray remains the first
      line exam to realize. It can suggest the diagnosis on the appearance and location
      of the lesions. CT scan is recommended for the positive diagnosis in case of
      discrepancy between clinical and radiographic signs, as for the diagnosis of
      parenchymal, vascular, lymph nodes, pleural, parietal or mediastinal
      complications. It is also essential for the evaluation of parenchyma sequelae.
      MRI and PET-scan have limited indications. The purpose of this article is to
      illustrate different radiological forms of chest tuberculosis, its sequelae and
      complications and to highlight the role of each imaging technique in the
      patient's management. 

PMID- 24874405
TI  - [Small cell lung cancer associated with paraneoplastic bullous pemphigoid].
AB  - The broncho-pulmonary small cell carcinoma is the most common cancer provider
      paraneoplastic syndrome especially neurological and endocrine but also cutaneous
      syndrome. Paraneoplastic dermatosis do not result from a direct extension of
      cancer and are not metastases, but their presence is suggestive of an underlying
      tumor. The evolution of the dermatosis is parallel to that of cancer: treating
      cancer results in the regression of cutaneous manifestations. We report an
      observation of a 44-year-old smoker, who was hospitalized for a tissue excavated
      process associated with bullous dermatosis. The transmural puncture biopsy finds
      small cell carcinoma. The skin biopsy objective bullous pemphigoid. The evolution
      under chemotherapy was marked regression of bullous lesions and the patient died
      later after metastatic extension. Cutaneous paraneoplastic syndrome appears only
      in a minority of cancer patients, but its recognition is very important for early
      diagnosis. 

PMID- 24874406
TI  - [pT4 non-small cell lung cancer: Surgical characteristics in present practice].
AB  - INTRODUCTION: pT4 is a group of miscellaneous tumors: our goal was to revisit
      their surgical reality. METHODS: The different characteristics and prognostic
      factors of lung pT4 (n=403) were analysed according to three subgroups: G1 - by
      direct extension; G2 - by nodule in other ipsilateral lobe; G3 - because of both.
      RESULTS: There were 332 males and 71 females mean aged 61.5 years. Surgery
      [exploratory: 89 (22.1 %), lobectomy: 149 (37 %), pneumonectomy: 169 (41.9 %)]
      was followed by 26 postoperative deaths (6.5 %), 82 complications (20.3 %) and
      concerned few pN0 (47.6 %). G1 (n=196) and G3 (n=53) were not different. By
      comparison with them, G2 (n=53) were mainly females (24?13 %), with less
      explorative thoracotomy (2.6?34 %), more complete R0 resections (77?29 %), less
      pneumonectomy (31?47 %), more small sized tumors (mean: 37?57 mm), more
      adenocarcinoma (67?32 %), more N0 tumors (48?31.7 %) and stages IIIA disease
      (46.7?56 %). G2 5-year survival rates were higher (G2: 22 %; G1: 13 %; G3: 15 %);
      G1 rates depended of the invaded structure (20.9 % for the vertebra down to 0 %
      for the esophagus and carina). pN2 rates were not very high but not different
      between groups (G1: 13.6 %; G2: 15.6 %; G3: 14.3 %; P=0.52). Multivariate
      analysis demonstrated completeness and type of resection, stage and age as
      independent factors of prognosis. CONCLUSION: Surgery for pT4 is justified
      provided rigorous selection of extension forms. However, assimilating extension
      and ipsilateral lobe nodule in a same group does not obey to surgical reality.

PMID- 24874407
TI  - Automated classification of radiology reports to facilitate retrospective study
      in radiology.
AB  - Retrospective research is an import tool in radiology. Identifying imaging
      examinations appropriate for a given research question from the unstructured
      radiology reports is extremely useful, but labor-intensive. Using the machine
      learning text-mining methods implemented in LingPipe [1], we evaluated the
      performance of the dynamic language model (DLM) and the Naive Bayesian (NB)
      classifiers in classifying radiology reports to facilitate identification of
      radiological examinations for research projects. The training dataset consisted
      of 14,325 sentences from 11,432 radiology reports randomly selected from a
      database of 5,104,594 reports in all disciplines of radiology. The training
      sentences were categorized manually into six categories (Positive, Differential,
      Post Treatment, Negative, Normal, and History). A 10-fold cross-validation [2]
      was used to evaluate the performance of the models, which were tested in
      classification of radiology reports for cases of sellar or suprasellar masses and
      colloid cysts. The average accuracies for the DLM and NB classifiers were 88.5%
      with 95% confidence interval (CI) of 1.9% and 85.9% with 95% CI of 2.0%,
      respectively. The DLM performed slightly better and was used to classify 1,397
      radiology reports containing the keywords "sellar or suprasellar mass", or
      "colloid cyst". The DLM model produced an accuracy of 88.2% with 95% CI of 2.1%
      for 959 reports that contain "sellar or suprasellar mass" and an accuracy of
      86.3% with 95% CI of 2.5% for 437 reports of "colloid cyst". We conclude that
      automated classification of radiology reports using machine learning techniques
      can effectively facilitate the identification of cases suitable for retrospective
      research.

PMID- 24874408
TI  - Secured telemedicine using region-based watermarking with tamper localization.
AB  - Medical images exchanged over public networks require a methodology to provide
      confidentiality for the image, authenticity of the image ownership and source of
      origin, and image integrity verification. To provide these three security
      requirements, we propose in this paper a region-based algorithm based on multiple
      watermarking in the frequency and spatial domains. Confidentiality and
      authenticity are provided by embedding robust watermarks in the region-of-non
      interest (RONI) of the image using a blind scheme in the discrete wavelet
      transform and singular value decomposition domain (DWT-SVD). On the other hand,
      integrity is provided by embedding local fragile watermarks in the region-of
      interest (ROI) of the image using a reversible scheme in the spatial domain. The
      integrity provided by the proposed algorithm is implemented on a block-level of
      the partitioned-image, thus enabling localized detection of tampered regions. The
      algorithm was evaluated with respect to imperceptibility, robustness, capacity,
      and tamper localization capability, using MRI, Ultrasound, and X-ray gray-scale
      medical images. Performance results demonstrate the effectiveness of the proposed
      algorithm in providing the required security services for telemedicine
      applications. 

PMID- 24874409
TI  - Patent foramen ovale and stroke in intermediate-risk pulmonary embolism.
AB  - BACKGROUND: Patent foramen ovale (PFO) in pulmonary embolism (PE) is associated
      with an increased risk of complications. However, little is known about PFO and
      ischemic stroke prevalence, particularly in acute intermediate-risk PE. In
      addition, in this context, the so-called "gold standard" method of PFO diagnosis
      remains unknown. We aimed to evaluate PFO and ischemic stroke prevalence and
      determine which of transesophageal echocardiography (TEE) or transthoracic
      echocardiography (TTE) is the best PFO diagnostic method in this context.
      METHODS: We conducted a prospective monocentric study of consecutive patients
      with intermediate-risk PE in whom a TEE and TTE with contrast were performed.
      Brain MRI was used to confirm clinically obvious strokes or to diagnose
      subclinical ones. RESULTS: Forty-one patients with intermediate-risk PE were
      identified over a 9-month period. Contrast TEE revealed PFO in 56.1%, whereas
      contrast TTE showed PFO in only 19.5% (P < .001). Of note, all PFOs observed with
      TTE were also diagnosed by TEE. Ischemic stroke occurred in 17.1% and was always
      associated with PFO and large shunt. CONCLUSIONS: PFO and related ischemic
      strokes are frequent in intermediate-risk PE. TEE is much more efficient than TTE
      for PFO diagnosis. Considering the high risk of intracranial bleeding with
      thrombolysis in PE, which may be partly due to hemorrhagic transformation of
      subclinical strokes, screening PFO with TEE should be considered in intermediate
      risk PE when thrombolytic treatment is discussed.

PMID- 24874410
TI  - A multifactorial role for P. falciparum malaria in endemic Burkitt's lymphoma
      pathogenesis.
AB  - Endemic Burkitt's lymphoma (eBL) arises from the germinal center (GC). It is a
      common tumor of young children in tropical Africa and its occurrence is closely
      linked geographically with the incidence of P. falciparum malaria. This
      association was noted more than 50 years ago. Since then we have learned that eBL
      contains the oncogenic herpes virus Epstein-Barr virus (EBV) and a defining
      translocation that activates the c-myc oncogene. However the link to malaria has
      never been explained. Here we provide evidence for a mechanism arising in the GC
      to explain this association. Accumulated evidence suggests that eBL arises in the
      GC when deregulated expression of AID (Activation-induced cytidine deaminase)
      causes a c-myc translocation in a cell latently infected with Epstein-Barr virus
      (EBV). Here we show that P. falciparum targets GC B cells via multiple pathways
      to increase the risk of eBL. 1. It causes deregulated expression of AID, thereby
      increasing the risk of a c-myc translocation. 2. It increases the number of B
      cells transiting the GC. 3. It dramatically increases the frequency of these
      cells that are infected with EBV and therefore protected from c-myc induced
      apoptosis. We propose that these activities combine synergistically to
      dramatically increase the incidence of eBL in individuals infected with malaria. 

PMID- 24874412
TI  - Brief report #3: building a rural community caregiver network: student learning
      in small town America.
AB  - The Rural Caregiver Network Project in Eastern Maine is a prime example of
      indigenous coalition-building in a region struggling to ensure that vulnerable
      older adults can age-in-place and manage with scarce resources. Through this
      innovative initiative, a range of elder caregiver interventions were mobilized,
      coordinated, and sustained in a rural two-county region in Maine, including
      navigator services, adult day care, information and referral, caregiver support
      groups, a caregiver resource center, and caregiver skills-building workshops. The
      endorsement of participatory research, evaluation, and programming principles
      enabled undergraduate and graduate social work students to assume major roles in
      all aspects of project planning, implementation, and assessment while remaining
      grounded in the realities of rural life. Competence in such a generalist
      gerontological social work practice perspective is critical in small towns and
      nonmetropolitan communities. 

PMID- 24874414
TI  - Preoperative maximum oxygen consumption is associated with prognosis after
      pulmonary resection in stage I non-small cell lung cancer.
AB  - BACKGROUND: The objective of this investigation was to evaluate whether maximum
      oxygen consumption (VO2max) is a reliable prognostic factor after lung resection
      for pathologic stage I non-small cell lung cancer (NSCLC). METHODS: Observational
      analysis of 157 patients undergoing pulmonary lobectomy or segmentectomy for
      pathologic stage I (T1 or T2-N0 only) NSCLC, with preoperative measurement of
      Vo2max and complete follow-up (2006-2011). Survival was calculated by the Kaplan
      Meier method. The log-rank test was used to assess differences in survival
      between groups. The relationships between survival and several baseline and
      clinical variables were determined by Cox multivariate analyses. RESULTS: The
      median follow-up time was 40 months. The average preoperative Vo2max was 16.1
      mL/kg . min and 69% of predicted value. Sixty-two (40%) patients had a Vo2max
      below 60%. The median and 5-year overall survivals of patients with preoperative
      Vo2max above 60% were significantly longer than in those with Vo2max below 60%
      (median not reached vs 48 months: 73% vs 40%, p=0.0004). Cox regression model
      showed that an age older than 70 years (p=0.005, hazard ratio 2.3) and Vo2max
      below 60% (p=0.001, hazard ratio 2.4) were independent prognostic factors
      significantly associated with overall survival. Cancer-specific survival was also
      longer in patients with Vo2max above 60% (81% vs 61%, p=0.01). CONCLUSIONS:
      Exercise tolerance may influence the physiologic outcomes associated with cancer
      that can potentially affect survival. Physical rehabilitation aimed at improving
      exercise tolerance can possibly improve the long-term prognosis after operations
      for lung cancer.

PMID- 24874413
TI  - Detailed analysis of temporal features on contrast enhanced ultrasound may help
      differentiate intrahepatic cholangiocarcinoma from hepatocellular carcinoma in
      cirrhosis.
AB  - AIM: To verify if detailed analysis of temporal enhancement patterns on contrast
      enhanced ultrasound (CEUS) may help differentiate intrahepatic cholangiocarcinoma
      (ICC) from hepatocellular carcinoma (HCC) in cirrhosis. METHODS: Thirty three ICC
      and fifty HCC in cirrhosis were enrolled in this study. The contrast kinetics of
      ICC and HCC was analyzed and compared. RESULTS: Statistical analysis did not
      reveal significant difference between ICC and HCC in the time of contrast first
      appearance and arterial peak maximum time. ICC displayed much earlier washout
      than that of HCC (47.93+/-26.45 seconds vs 90.86+/-31.26 seconds) in the portal
      phase, and most ICC (87.9%) showed washout before 60 seconds than HCC (16.0%).
      Much more ICC (78.8%) revealed marked washout than HCC (12.0%) while most HCC
      (88.0%) showed mild washout or no washout in late part of the portal phase (90
      120 seconds). Twenty six out of thirty three ICC (78.8%) demonstrated both early
      washout(<60 seconds) and marked washout in late part of the portal phase,
      whereas, only six of fifty HCC (12.0%)showed these temporal enhancement features
      (p = 0.000).When both early washout and marked washout in the portal phase are
      taken as diagnostic criterion for ICC, the diagnostic sensitivity, specificity,
      positive predictive value, negative predictive value and accuracy were
      78.8%,88.0%,81.3%,86.3%,and 84.3% respectively by CEUS. CONCLUSIONS: Analysis of
      detailed temporal enhancement features on CEUS is helpful differentiate ICC from
      HCC in cirrhosis.If a nodule in cirrhotic liver displays hyper-enhancement in the
      arterial phase followed by early and marked washout in the portal phase, the
      nodule is highly suspicious of ICC rather than HCC.

PMID- 24874420
TI  - Impaired reward processing by anterior cingulate cortex in children with
      attention deficit hyperactivity disorder.
AB  - Decades of research have examined the neurocognitive mechanisms of cognitive
      control, but the motivational factors underlying task selection and performance
      remain to be elucidated. We recently proposed that anterior cingulate cortex
      (ACC) utilizes reward prediction error signals carried by the midbrain dopamine
      system to learn the value of tasks according to the principles of hierarchical
      reinforcement learning. According to this position, disruption of the ACC
      dopamine interface can disrupt the selection and execution of extended, task
      related behaviors. To investigate this issue, we recorded the event-related brain
      potential (ERP) from children with attention deficit hyperactivity disorder
      (ADHD), which is strongly associated with ACC-dopamine dysfunction, and from
      typically developing children while they navigated a simple "virtual T-maze" to
      find rewards. Depending on the condition, the feedback stimuli on each trial
      indicated that the children earned or failed to earn either money or points. We
      found that the reward positivity, an ERP component proposed to index the impact
      of dopamine-related reward signals on ACC, was significantly larger with money
      feedback than with points feedback for the children with ADHD, but not for the
      typically developing children. These results suggest that disruption of the ACC
      dopamine interface may underlie the impairments in motivational control observed
      in childhood ADHD. 

PMID- 24874421
TI  - The attribution of value-based attentional priority in individuals with
      depressive symptoms.
AB  - The capture of attention by stimuli previously associated with reward has been
      demonstrated across a wide range of studies. Such value-based attentional
      priority appears to be robust, and cases where reward feedback fails to modulate
      subsequent attention have not been reported. However, individuals differ in their
      sensitivity to external rewards, and such sensitivity is abnormally blunted in
      depression. Here, we show that depressive symptomology is accompanied by
      insensitivity to value-based attentional bias. We replicate attentional capture
      by stimuli previously associated with reward in a control sample and show that
      these same reward-related stimuli do not capture attention in individuals
      experiencing symptoms of depression. This sharp contrast in performance indicates
      that value-based attentional biases depend on the normal functioning of the
      brain's reward system and suggests that a failure to preferentially attend to
      reward-related information may play a role in the experience of depression.

PMID- 24874424
TI  - Synthesis of di- and tetranuclear oxido-molybdenum(V) complexes containing p
      toluenesulfonates as ligands: a joint spectroscopic, crystallographic and
      computational study.
AB  - The 1 : 1 reaction of MoCl5 with 1,4-Me(SO3Me)C6H4 led to the isolation of
      crystalline Mo2O2Cl6[MU-kappa(2)-1,4-Me(SO3Me)C6H4], 1, in low yields. Attempts
      to reproduce the synthesis of 1 from MoOCl3/1,4-Me(SO3Me)C6H4 resulted in the
      good-yield formation of [MoOCl2(MU-Cl)(kappa(1)-1,4-Me(SO3Me)C6H4)]2, 2. The 1 :
      1 reaction of MoCl5 with 1,4-Me(SO3H)C6H4.H2O selectively yielded Mo4O4Cl8[MU3
      1,4-Me(SO3)C6H4]4, 3. Compounds 1 and 3 were characterized by X-ray
      diffractometry; moreover DFT calculations were carried out on 1-3 in order to
      shed light on their thermodynamic and structural features. 

PMID- 24874422
TI  - Cardiomyocyte maturation: It takes a village to raise a kid.

PMID- 24874423
TI  - Diabetes, microRNAs and exosomes: Les liaisons dangereuses.

PMID- 24874426
TI  - A blind human expert echolocator shows size constancy for objects perceived by
      echoes.
AB  - Some blind humans make clicking noises with their mouth and use the reflected
      echoes to perceive objects and surfaces. This technique can operate as a crude
      substitute for vision, allowing human echolocators to perceive silent, distal
      objects. Here, we tested if echolocation would, like vision, show size constancy.
      To investigate this, we asked a blind expert echolocator (EE) to echolocate
      objects of different physical sizes presented at different distances. The EE
      consistently identified the true physical size of the objects independent of
      distance. In contrast, blind and blindfolded sighted controls did not show size
      constancy, even when encouraged to use mouth clicks, claps, or other signals.
      These findings suggest that size constancy is not a purely visual phenomenon, but
      that it can operate via an auditory-based substitute for vision, such as human
      echolocation. 

PMID- 24874428
TI  - Super-suppression of mitochondrial reactive oxygen species signaling impairs
      compensatory autophagy in primary mitophagic cardiomyopathy.
AB  - RATIONALE: Mitochondrial reactive oxygen species (ROS) are implicated in aging,
      chronic degenerative neurological syndromes, and myopathies. On the basis of free
      radical hypothesis, dietary, pharmacological, and genetic ROS suppression has
      been tested to minimize tissue damage, with remarkable therapeutic efficacy. The
      effects of mitochondrial-specific ROS suppression in primary mitophagic
      dysfunction are unknown. OBJECTIVE: An in vivo dose-ranging analysis of ROS
      suppression in an experimental cardiomyopathy provoked by defective mitochondrial
      clearance. METHODS AND RESULTS: Mice lacking mitofusin 2 (Mfn2) in hearts have
      impaired parkin-mediated mitophagy leading to accumulation of damaged ROS
      producing organelles and progressive heart failure. As expected, cardiomyocyte
      directed expression of mitochondrial-targeted catalase at modest levels
      normalized mitochondrial ROS production and prevented mitochondrial
      depolarization, respiratory impairment, and structural degeneration in Mfn2 null
      hearts. In contrast, catalase expression at higher levels that supersuppressed
      mitochondrial ROS failed to improve either mitochondrial fitness or
      cardiomyopathy, revealing that ROS toxicity is not the primary mechanism for
      cardiac degeneration. Lack of benefit from supersuppressing ROS was associated
      with failure to invoke secondary autophagic pathways of mitochondrial quality
      control, revealing a role for ROS signaling in mitochondrial clearance.
      Mitochondrial permeability transition pore function was normal, and genetic
      inhibition of mitochondrial permeability transition pore function did not alter
      mitochondrial or cardiac degeneration, in Mfn2 null hearts. CONCLUSIONS: Local
      mitochondrial ROS (1) contribute to mitochondrial degeneration and (2) activate
      mitochondrial quality control mechanisms. A therapeutic window for mitochondrial
      ROS suppression should minimize the former while retaining the latter, which we
      achieved by expressing lower levels of catalase.

PMID- 24874427
TI  - FOXO1-mediated activation of Akt plays a critical role in vascular homeostasis.
AB  - RATIONALE: Forkhead box-O transcription factors (FoxOs) transduce a wide range of
      extracellular signals, resulting in changes in cell survival, cell cycle
      progression, and several cell type-specific responses. FoxO1 is expressed in many
      cell types, including endothelial cells (ECs). Previous studies have shown that
      Foxo1 knockout in mice results in embryonic lethality at E11 because of impaired
      vascular development. In contrast, somatic deletion of Foxo1 is associated with
      hyperproliferation of ECs. Thus, the precise role of FoxO1 in the endothelium
      remains enigmatic. OBJECTIVE: To determine the effect of endothelial-specific
      knockout and overexpression of FoxO1 on vascular homeostasis. METHODS AND
      RESULTS: We show that EC-specific disruption of Foxo1 in mice phenocopies the
      full knockout. Although endothelial expression of FoxO1 rescued otherwise Foxo1
      null animals, overexpression of constitutively active FoxO1 resulted in increased
      EC size, occlusion of capillaries, elevated peripheral resistance, heart failure,
      and death. Knockdown of FoxO1 in ECs resulted in marked inhibition of basal and
      vascular endothelial growth factor-induced Akt-mammalian target of rapamycin
      complex 1 (mTORC1) signaling. CONCLUSIONS: Our findings suggest that in mice,
      endothelial expression of FoxO1 is both necessary and sufficient for embryonic
      development. Moreover, FoxO1-mediated feedback activation of Akt maintains growth
      factor responsive Akt/mTORC1 activity within a homeostatic range.

PMID- 24874430
TI  - Lactobacillus pentosus strain LPS16 produces lactic acid, inhibiting multidrug
      resistant Helicobacter pylori.
AB  - BACKGROUND/PURPOSE: Helicobacter pylori is a human gastric pathogen. Antibiotic
      resistance of H. pylori has become a problem increasing the failure of H. pylori
      eradication. Therefore alternative approaches are required. The aim of this study
      was to evaluate the anti-H. pylori activity of Lactobacillus pentosus strain
      LPS16 and the mechanism of its killing effect. METHODS: The anti-H. pylori
      activity of LPS16 was determined by the disc diffusion test and time killing
      assay. High-performance liquid chromatography analysis was used to analyze the
      secreted compounds of LPS16. Sixty H. pylori strains isolated from different
      gastric diseases, having different antibiotic susceptibility were collected to
      analyze the spectrum of anti-H. pylori activity of LPS16. Adhesion ability of
      LPS16 to gastric epithelial cell lines was assayed by flow cytometry. RESULTS:
      The anti-H. pylori activity of LPS16 depended on the secreted component, and
      lactic acid mediated bactericidal activity against H. pylori. The bactericidal
      activity did not vary significantly among the strains isolated from different
      diseases having different antibiotic susceptibility. Moreover, LPS16 can adhere
      on gastric epithelial cell lines AKG and MKN45. CONCLUSION: L. pentosus strain
      LPS16 had the broad-spectrum anti-H. pylori activity, suggesting that it can be
      used to prevent H. pylori infection.

PMID- 24874431
TI  - Systemic lupus erythematosus and thyroid disease: A 10-year study.
AB  - BACKGROUND: This large-scale study aims to analyze the association of systemic
      lupus erythematosus (SLE) with thyroid diseases. METHODS: In this retrospective,
      nationwide cohort study, 1633 newly diagnosed SLE patients from the National
      Health Insurance Research Database in 2000 were examined and data on patients
      with diagnoses of hyperthyroidism, hypothyroidism, and autoimmune thyroiditis
      were collected from 2000 to 2009. We subdivided these SLE patients by the
      presence of overlap syndrome. Comparison with 6532 age- and sex-matched controls
      was performed. RESULTS: The cumulative incidence of thyroid disease in SLE
      patients was lower than in controls (8.1% vs. 16.9%, p < 0.001). Among SLE
      patients, 39.7% had overlap syndrome. The overlap syndrome group had a higher
      cumulative incidence of thyroid diseases (10.96% vs. 4.57%, p < 0.0001),
      hypothyroidism (3.86% vs. 1.93%, p = 0.017), and autoimmune thyroiditis (4.63%
      vs. 0.71%, p < 0.0001) than SLE patients without overlap syndrome. Comparing the
      data with the non-SLE-matched control group by logistic regression model revealed
      a decreased risk of thyroid diseases with odds ratios (ORs) of 0.25 and 0.62 [95%
      confidence interval (CI) 0.18-0.33, 0.48-0.80], and hyperthyroidism with ORs of
      0.21 and 0.30 (95% CI 0.14-0.31, 0.20-0.45) in SLE patients without and with
      overlap syndrome. SLE patients without overlap syndrome had a lower risk of
      hypothyroidism with an OR of 0.53 (95% CI 0.53-0.86) and autoimmune thyroiditis
      with an OR of 0.26 (95% CI 0.12-0.56). SLE patients with overlap syndrome showed
      a similar risk of hypothyroidism with an OR of 0.92 (95% CI 0.66-1.53) and a
      higher risk of autoimmune thyroiditis with OR of 1.69 (95% CI 1.14-2.51).
      CONCLUSION: SLE patients had a significantly lower rate of thyroid diseases and
      hyperthyroidism than matched controls. Among SLE patients, risks of
      hypothyroidism and autoimmune thyroiditis were different in the presence of
      overlap syndrome. This finding is novel and important for clinical practices.

PMID- 24874429
TI  - Rapamycin-resistant poly (ADP-ribose) polymerase-1 overexpression is a potential
      therapeutic target in lymphangioleiomyomatosis.
AB  - Lymphangioleiomyomatosis (LAM) is a female-predominant cystic lung disease that
      can lead to respiratory failure. LAM cells typically have inactivating tuberous
      sclerosis complex 2 (TSC2) mutations and mammalian target of rapamycin (mTOR)
      complex (mTORC) 1 activation. Clinical response to the mTORC1 inhibitors has been
      limited, prompting a search for additional therapy for LAM. In this study, we
      investigated the impact of TSC2 on the expression of poly (ADP-ribose) polymerase
      (PARP)-1 that initiates the DNA repair pathway, and tested the efficacy of PARP1
      inhibitors in the survival of TSC2-deficient (TSC2(-)) cells. We analyzed
      publicly available expression arrays of TSC2(-) cells and validated the findings
      using real-time RT-PCR, immunoblotting, and immunohistochemistry. We examined the
      impact of rapamycin and Torin 1 on PARP1 expression. We also tested the effect of
      PARP1 inhibitors, 8-hydroxy-2-methylquinazoline-4-one and 3,4-dihydro-5[4-(1
      piperindinyl)butoxy]-1(2H)-isoquinoline, on the survival of TSC2(-) cells. We
      identified the up-regulation of PARP1 in TSC2(-) cells relative to cells in which
      wild-type TSC2 has been reintroduced (TSC2-addback [TSC2(+)] cells). The
      transcript levels of PARP1 in TSC2(-) cells were not affected by rapamycin. PARP1
      levels were increased in TSC2(-) cells, xenograft tumors of rat-derived TSC2(-)
      cells, renal cystadenomas from Tsc2(+/-) mice, and human LAM nodules. RNA
      interference of mTOR failed to reduce PARP1 levels. Proliferation and survival of
      TSC2(-) cells was reduced in response to PARP1 inhibitor treatment, more so than
      TSC2(+) cells. TSC2(-) cells exhibit higher levels of PARP1 relative to TSC2(+)
      cells in an mTOR-insensitive manner. PARP1 inhibitors selectively suppress the
      growth and induce apoptosis of TSC2(-) cells from patients with LAM. Targeting
      PARP1 may be beneficial in the treatment of LAM and other neoplasm with mTORC1
      activation.

PMID- 24874433
TI  - Selective protection of normal cells during chemotherapy by RY4 peptides.
AB  - Mitochondrial targeted Szeto-Schiller (SS) peptides have recently gained
      attention for their antioxidative stress ability; however, the functional
      variations between normal and cancer cells have not been determined. Here, we
      report the results of such experiments conducted with a newly designed class of
      peptide called RY4, which is based on SS peptide sequence characteristics. The
      RY4 peptide exhibits distinct differences in antioxidative stress response
      between normal and cancer cells when challenged with chemotherapeutics like the
      glycolytic inhibitor dichloroacetate (DCA), the platinating agent carboplatin,
      and the DNA damage inducer doxorubicin. Interestingly, only normal human cells
      were protected by the RY4 peptide and catalase (CAT) activity was significantly
      enhanced in normal but not tumor cells when incubated with RY4. Pull-down,
      coimmunoprecipitation, and LC/MS-MS proteomic analysis demonstrated that RY4 and
      catalase are capable of forming protein complexes. Finally, in vivo efficacy was
      evaluated by intraperitoneal administration of RY4 into a lung cancer xenograft
      model, which revealed significant myocardiocyte protection from doxorubicin
      induced cardiotoxicity without diminishing doxorubicin's tumoricidal effects.
      Taken together, RY4 offers selective protection to normal cells from chemotherapy
      induced toxicity by enhancing the activity of cellular antioxidant enzymes.
      IMPLICATIONS: RY4 peptides selectively reduce chemotherapeutic-induced oxidative
      stress and represent a new class of chemoprotective agents with clinical
      potential.

PMID- 24874432
TI  - Involvement of extracellular vesicle long noncoding RNA (linc-VLDLR) in tumor
      cell responses to chemotherapy.
AB  - Hepatocellular cancer (HCC) is a highly treatment-refractory cancer and is also
      highly resistant to adverse cellular stress. Although cell behavior can be
      modulated by noncoding RNAs (ncRNA) within extracellular vesicles (EV), the
      contributions of long noncoding RNAs (lncRNAs) are largely unknown. To this end,
      the involvement and functional roles of lncRNAs contained within EVs during
      chemotherapeutic stress in human HCC were determined. Expression profiling
      identified a subset of lncRNAs that were enriched in tumor cell-derived vesicles
      released from two different cell lines. Of these, lincRNA-VLDLR (linc-VLDLR) was
      significantly upregulated in malignant hepatocytes. Exposure of HCC cells to
      diverse anticancer agents such as sorafenib, camptothecin, and doxorubicin
      increased linc-VLDLR expression in cells as well as within EVs released from
      these cells. Incubation with EVs reduced chemotherapy-induced cell death and also
      increased linc-VLDLR expression in recipient cells. RNAi-mediated knockdown of
      linc-VLDLR decreased cell viability and abrogated cell-cycle progression.
      Moreover, knockdown of VLDLR reduced expression of ABCG2 (ATP-binding cassette,
      subfamily G member 2), whereas overexpression of this protein reduced the effects
      of VLDLR knockdown on sorafenib-induced cell death. Here, linc-VLDLR is
      identified as an EV-enriched lncRNA that contributes to cellular stress
      responses. IMPLICATIONS: These findings provide new insight into the role of EVs
      and demonstrate the capacity of lncRNAs to mediate chemotherapeutic stress
      response in HCC.

PMID- 24874437
TI  - Dissolution without disappearing: multicomponent gas exchange for CO2 bubbles in
      a microfluidic channel.
AB  - We studied the dissolution dynamics of CO2 gas bubbles in a microfluidic channel,
      both experimentally and theoretically. In the experiments, spherical CO2 bubbles
      in a flow of a solution of sodium dodecyl sulfate (SDS) first shrink rapidly
      before attaining an equilibrium size. In the rapid dissolution regime, the time
      to obtain a new equilibrium is 30 ms regardless of SDS concentration, and the
      equilibrium radius achieved varies with the SDS concentration. To explain the
      lack of complete dissolution, we interpret the results by considering the effects
      of other gases (O2, N2) that are already dissolved in the aqueous phase, and we
      develop a multicomponent dissolution model that includes the effect of surface
      tension and the liquid pressure drop along the channel. Solutions of the model
      for a stationary gas bubble show good agreement with the experimental results,
      which lead to our conclusion that the equilibrium regime is obtained by gas
      exchange between the bubbles and liquid phase. Also, our observations from
      experiments and model calculations suggest that SDS molecules on the gas-liquid
      interface form a diffusion barrier, which controls the dissolution behaviour and
      the eventual equilibrium radius of the bubble. 

PMID- 24874434
TI  - The natural history of biocatalytic mechanisms.
AB  - Phylogenomic analysis of the occurrence and abundance of protein domains in
      proteomes has recently showed that the alpha/beta architecture is probably the
      oldest fold design. This holds important implications for the origins of
      biochemistry. Here we explore structure-function relationships addressing the use
      of chemical mechanisms by ancestral enzymes. We test the hypothesis that the
      oldest folds used the most mechanisms. We start by tracing biocatalytic
      mechanisms operating in metabolic enzymes along a phylogenetic timeline of the
      first appearance of homologous superfamilies of protein domain structures from
      CATH. A total of 335 enzyme reactions were retrieved from MACiE and were mapped
      over fold age. We define a mechanistic step type as one of the 51 mechanistic
      annotations given in MACiE, and each step of each of the 335 mechanisms was
      described using one or more of these annotations. We find that the first two
      folds, the P-loop containing nucleotide triphosphate hydrolase and the NAD(P)
      binding Rossmann-like homologous superfamilies, were alpha/beta architectures
      responsible for introducing 35% (18/51) of the known mechanistic step types. We
      find that these two oldest structures in the phylogenomic analysis of protein
      domains introduced many mechanistic step types that were later combinatorially
      spread in catalytic history. The most common mechanistic step types included
      fundamental building blocks of enzyme chemistry: "Proton transfer," "Bimolecular
      nucleophilic addition," "Bimolecular nucleophilic substitution," and
      "Unimolecular elimination by the conjugate base." They were associated with the
      most ancestral fold structure typical of P-loop containing nucleotide
      triphosphate hydrolases. Over half of the mechanistic step types were introduced
      in the evolutionary timeline before the appearance of structures specific to
      diversified organisms, during a period of architectural diversification. The
      other half unfolded gradually after organismal diversification and during a
      period that spanned ~2 billion years of evolutionary history. 

PMID- 24874435
TI  - Size-dependent distribution of radiocesium in riverbed sediments and its
      relevance to the migration of radiocesium in river systems after the Fukushima
      Daiichi Nuclear Power Plant accident.
AB  - We investigated the particle size distribution of radiocesium in riverbed
      sediments after the Fukushima Daiichi Nuclear Power Plant accident. Riverbed
      sediments were collected in the Abukuma River system in Fukushima and Miyagi
      Prefectures. The collected sediments were separated into 11 fractions, ranging
      from granular size (>2000 MUm) to clay size (<2 MUm) fractions. Cesium-137
      concentrations were higher in the smaller particle size fractions, possibly
      reflecting specific surface areas and the mineralogy, in particular the clay
      mineral content. A gap in (137)Cs concentration was observed between the silt
      size and sand size fractions of riverbed sediments at downstream sites, whereas
      riverbed sediments at an upstream site did not show such a concentration gap. It
      is likely that selective transport of small particles in suspended state from
      upstream areas resulted in an accumulation of radiocesium in downstream areas. 

PMID- 24874438
TI  - Design, synthesis, and structure-activity relationship studies of novel thioether
      pleuromutilin derivatives as potent antibacterial agents.
AB  - A series of novel thioether pleuromutilin derivatives incorporating various
      heteroaromatic substituents into the C14 side chain have been reported. Structure
      activity relationship (SAR) studies resulted in compounds 52 and 55 with the most
      potent in vitro antibacterial activity among the series (MIC = 0.031-0.063
      MUg/mL). Further optimization to overcome the poor water solubility of compound
      55 resulted in compounds 87, 91, 109, and 110 possessing good in vitro
      antibacterial activity with increased hydrophilicity. Compound 114, the water
      soluble phosphate prodrug of compound 52, was also prepared and evaluated. Among
      the derivatives, compound 110 showed moderate pharmacokinetic profiles and good
      in vivo efficacy in both MSSA and MRSA systemic infection models. Compound 110
      was further evaluated in CYP450 inhibition assay and displayed intermediate in
      vitro inhibition of CYP3A4. 

PMID- 24874440
TI  - Emodin inhibits LPS-induced inflammatory response by activating PPAR-gamma in
      mouse mammary epithelial cells.
AB  - Emodin, an anthraquinone derivative isolated from the rhizomes of Rheum palmatum,
      has been reported to have a protective effect against lipopolysaccharide (LPS)
      induced mastitis. However, the underlying molecular mechanisms are not well
      understood. The aim of this study was to investigate the molecular mechanisms of
      emodin in modifying lipopolysaccharide (LPS)-induced signaling pathways in mouse
      mammary epithelial cells (MEC). The pro-inflammatory cytokines were determined by
      ELISA. Nuclear factor-kappaB (NF-kappaB), inhibitory kappa B (IkappaBalpha)
      protein, p38, extracellular signal-regulated kinase (ERK), c-Jun N-terminal
      kinase (JNK) and PPAR-gamma were determined by Western blotting. The results
      showed that emodin suppressed tumor necrosis factor-alpha (TNF-alpha),
      interleukin-6 (IL-6), iNOS and COX-2 expression. We also found that emodin
      inhibited LPS-induced NF-kappaB activation, IkappaBalpha degradation,
      phosphorylation of ERK, JNK and P38. Furthermore, emodin could activate PPAR
      gamma and the anti-inflammatory effects of emodin can be reversed by GW9662, a
      specific antagonist for PPAR-gamma. In conclusion, our results demonstrate that
      emodin activates PPAR-gamma, thereby attenuating LPS-induced inflammatory
      response.

PMID- 24874439
TI  - Oleic acid is a precursor of linoleic acid and the male sex pheromone in Nasonia
      vitripennis.
AB  - Linoleic acid (C18:2(Delta9,12), LA) is crucial for many cell functions in
      organisms. It has long been a paradigm that animals are unable to synthesize LA
      from oleic acid (C18:1(Delta9), OA) because they were thought to miss Delta(12)
      desaturases for inserting a double bound at the Delta(12)-position. Today it is
      clear that this is not true for all animals because some insects and other
      invertebrates have been demonstrated to synthesize LA. However, the ability to
      synthesize LA is known in only five insect orders and no examples have been
      reported so far in the Hymenoptera. LA plays a particular role in the parasitic
      wasp Nasonia vitripennis, because it is the precursor of the male sex pheromone
      consisting of (4R,5R)- and (4R,5S)-5-hydroxy-4-decanolides. Here we demonstrate
      by stable isotope labeling that N. vitripennis is able to incorporate externally
      applied fully (13)C-labeled OA into the male sex pheromone suggesting that they
      convert initially OA into LA. To verify this assumption, we produced fly hosts
      (Lucilia caesar) which were experimentally enriched in (13)C-labeled OA and
      reared male parasitoids on these hosts. Chemical analysis of transesterified
      lipid raw extracts from hosts and parasitoids revealed that N. vitripennis but
      not L. caesar contained (13)C-labeled LA methyl ester. Furthermore, male wasps
      from the manipulated hosts produced significant amounts of (13)C-labeled sex
      pheromone. These results suggest that N. vitripennis possesses a Delta(12)
      desaturase. The additional fitness relevant function as pheromone precursor might
      have favored the evolution of LA biosynthesis in N. vitripennis to make the wasps
      independent of the formerly essential nutrient. 

PMID- 24874441
TI  - Effect of natural porcine surfactant in Staphylococcus aureus induced pro
      inflammatory cytokines and reactive oxygen species generation in monocytes and
      neutrophils from human blood.
AB  - Surfacen(r) is a clinical surfactant preparation of porcine origin. In the
      present study, we have evaluated the effect of Surfacen(r) in the modulation of
      oxidative burst in monocytes and neutrophils in human blood and pro-inflammatory
      cytokine production in peripheral blood mononuclear cells (PBMC). Reactive oxygen
      species (ROS) level was measured in monocytes and neutrophils by flow cytometry
      using 2,7-dichlorofluorescein diacetate (DCFH-DA) as substrate, while, tumor
      necrosis factor (TNF)-alpha and interleukin (IL)-6 levels were estimated in PBMC
      supernatant by enzyme-linked immunosorbent assays (ELISA). Our results show that
      Staphylococcus aureus-induced ROS level was slightly affected by Surfacen(r)
      added to whole blood monocytes and neutrophils. The time course experiments of
      pre-incubation with Surfacen(r) showed no significant increase of ROS level at
      2h; however, the ROS level decreased when pre incubated for 4h and 6h with
      Surfacen(r). Pre-incubation of PBMC cells with Surfacen(r) at 0.125 and 0.5mg/mL
      showed a dose-dependent suppression of TNF-alpha levels measured after 4h of S.
      aureus stimulation, an effect less impressive when cells were stimulated for 24h.
      A similar behavior was observed in IL-6 release. In summary, the present study
      provides experimental evidence supporting an anti-inflammatory role of
      Surfacen(r) in human monocytes and neutrophils in vitro.

PMID- 24874442
TI  - Carbon tetrachloride-induced hepatotoxicity in rat is reversed by treatment with
      riboflavin.
AB  - Liver is a vital organ for the detoxification of toxic substances present in the
      body and hepatic injury is associated with excessive exposure to toxicants. The
      present study was designed to evaluate the possible hepatoprotective effects of
      riboflavin against carbon tetrachloride (CCl4) induced hepatic injury in rats.
      Rats were divided into six groups. Hepatotoxicity was induced by the
      administration of a single intraperitoneal dose of CCl4 in experimental rats.
      Riboflavin was administered at 30 and 100mg/kg by oral gavage to test its
      protective effect on hepatic injury biochemically and histopathologically in the
      blood/liver and liver respectively. The administration of CCl4 resulted in marked
      alteration in serum hepatic enzymes (like AST, ALT and ALP), oxidant parameters
      (like GSH and MDA) and pro-inflammatory cytokine TNF-alpha release from blood
      leukocytes indicative of hepatic injury. Changes in serum hepatic enzymes,
      oxidant parameters and TNF-alpha production induced by CCl4 were reversed by
      riboflavin treatment in a dose dependent manner. Treatment with standard drug,
      silymarin also reversed CCl4 induced changes in biomarkers of liver function,
      oxidant parameters and inflammation. The biochemical observations were paralleled
      by histopathological findings in rat liver both in the case of CCl4 and treatment
      groups. In conclusion, riboflavin produced a protective effect against CCl4
      induced liver damage. Our study suggests that riboflavin may be used as a hepato
      protective agent against toxic effects caused by CCl4 and other chemical agents
      in the liver. 

PMID- 24874443
TI  - Finite element analysis to characterize how varying patellar loading influences
      pressure applied to cartilage: model evaluation.
AB  - A finite element analysis (FEA) modeling technique has been developed to
      characterize how varying the orientation of the patellar tendon influences the
      patellofemoral pressure distribution. To evaluate the accuracy of the technique,
      models were created from MRI images to represent five knees that were previously
      tested in vitro to determine the influence of hamstrings loading on
      patellofemoral contact pressures. Hamstrings loading increased the lateral and
      posterior orientation of the patellar tendon. Each model was loaded at 40 degrees
      , 60 degrees , and 80 degrees  of flexion with quadriceps force vectors
      representing the experimental loading conditions. The orientation of the patellar
      tendon was represented for the loaded and unloaded hamstrings conditions based on
      experimental measures of tibiofemoral alignment. Similar to the experimental
      data, simulated loading of the hamstrings within the FEA models shifted the
      center of pressure laterally and increased the maximum lateral pressure.
      Significant (p < 0.05) differences were identified for the center of pressure and
      maximum lateral pressure from paired t-tests carried out at the individual
      flexion angles. The ability to replicate experimental trends indicates that the
      FEA models can be used for future studies focused on determining how variations
      in the orientation of the patellar tendon related to anatomical or loading
      variations or surgical procedures influence the patellofemoral pressure
      distribution.

PMID- 24874445
TI  - Arrhythmic risk in rheumatoid arthritis: the driving role of systemic
      inflammation.
AB  - When compared to the general population, patients with rheumatoid arthritis (RA)
      have an overall standard mortality ratio of approximately two, with more than 50%
      of premature deaths attributable to cardiovascular disease (CVD). Moreover, RA
      patients were twice as likely to experience sudden cardiac death (SCD) compared
      with non-RA subjects, as a putative consequence of an increased incidence of
      malignant arrhythmias. Accordingly, mounting data indicate that in patients
      affected with RA the risk of developing rhythm disturbances, particularly
      tachyarrhythmias, is high. Although a number of papers reviewing the problem of
      cardiovascular involvement in RA are currently available, the main focus is on
      the mechanisms of accelerated atherosclerosis and related ischemic consequences
      in the clinical setting. On the contrary, only little consideration has been
      specifically given to the arrhythmic risk so far. In the light of this concern,
      in the present paper we reviewed the topic with the aim to put together the
      apparently fragmentary existing information, with particular attention to the
      putative role of chronic systemic inflammation characterizing the disease. In
      fact, although the underlying mechanisms accounting the arrhythmogenic substrate
      in RA are probably intricate, the leading role seems to be played by inflammatory
      activation, able to promote arrhythmias either indirectly, by accelerating the
      development of structural CVD, and directly by affecting cardiac
      electrophysiology. In this view, lowering inflammatory burden through an
      increasingly tight control of disease activity may represent the most effective
      intervention to reduce arrhythmic risk and prevent life-threatening complications
      in these patients. 

PMID- 24874444
TI  - A multi-level approach to investigate the control of an input device: application
      to a realistic pointing task.
AB  - This study investigates the subjects' performance during realistic conditions of
      control of a joystick. An adapted reciprocal aiming task consisting in driving a
      virtual vehicle along a slalom course as fast as possible was performed while
      accuracy constraints were manipulated. Realistic dynamical Interface Screen
      Relationship between the joystick displacements and the displacements of the
      vehicle was simulated. Vehicle displacements and motor activity (muscle activity
      and joint kinematics) were recorded. The results highlighted the applicability of
      the Fitts' law to more realistic conditions where the use of an input device is
      performed in an intensive control situation. Besides, biomechanical results
      suggested that neuromuscular responses were different regarding the direction of
      movement, whereas the performance at a behavioural level were not affected. Thus,
      this study demonstrates the interest in considering two different aspects of the
      user's performance (behavioural and biomechanical ones) to make a better
      agreement between the device design and users' needs. PRACTITIONER SUMMARY: This
      study considered two different aspects of the subject's performance in a
      realistic situation of speed-accuracy trade-off: the behavioural and motor
      activity. The necessity for the design of the future ergonomics pointing devices
      to meet the expectations of the neuromuscular system in order to facilitate their
      uses is highlighted.

PMID- 24874446
TI  - Isolation of a hexanuclear chromium cluster with a tetrahedral hydridic core and
      its catalytic behavior for ethylene oligomerization.
AB  - A chromium complex [2-(NHCH2PPh2)C5H4N]CrCl3.THF2 (1) of the ligand PyNHCH2PPh2
      has been synthesized, characterized, and examined for its catalytic behavior
      toward ethylene oligomerization. When complex 1 was treated with (i-Bu)3Al, an
      unprecedented divalent polyhydride chromium cluster MU,kappa(1),kappa(2),kappa(3)
      N,N,P-{[2-(NCH2PPh2)C5H4N]Cr(MU-H)}4[(MU-Cl)Cr(MU-Cl)Al(i-Bu)2Cl]2 (2) was
      obtained. The complex contains a Cr4H4 core, which is expected to be diamagnetic,
      and which remains coordinated to two additional divalent high-spin Cr atoms via
      bridging interactions. Two aluminate residues remain bonded to the peripheral
      chromium atoms. The structure, magnetism, and electronic configuration are herein
      discussed. 

PMID- 24874448
TI  - Early adrenaline for cardiac arrest.

PMID- 24874449
TI  - The eukaryotic N-end rule pathway: conserved mechanisms and diverse functions.
AB  - The N-end rule pathway of targeted proteolysis, which relates the stability of a
      protein to the nature of its N-terminus, has emerged as a key regulator of
      diverse processes in eukaryotes. Recent reports that N-terminally acetylated and
      methionine-initiating proteins can be targeted for degradation have uncovered
      novel branches of the pathway, and a wide range of protein substrates has now
      been identified in animals, fungi, and plants. Of particular interest is the
      finding that the N-end rule pathway mediates oxygen and nitric oxide (NO) sensing
      in plants and animals by controlling the stability of kingdom-specific
      substrates. These findings highlight how conserved degradation mechanisms of the
      N-end rule pathway underlie functional divergence throughout eukaryotes. 

PMID- 24874451
TI  - Paediatric drug delivery. Preface.

PMID- 24874447
TI  - Complementary diversification of dendritic cells and innate lymphoid cells.
AB  - Dendritic cells (DCs) are professional antigen presenting cells conventionally
      thought to mediate cellular adaptive immune responses. Recent studies have led to
      the recognition of a non-redundant role for DCs in orchestrating innate immune
      responses, and in particular, for DC subset-specific interactions with innate
      lymphoid cells (ILCs). Recently recognized as important effectors of early immune
      responses, ILCs develop into subsets which mirror the transcriptional and
      cytokine profile of their T cell subset counterparts. DC diversification into
      functional subsets provides for modules of pathogen sensing and cytokine
      production that direct pathogen-appropriate ILC and T cell responses. This review
      focuses on the recent advances in the understanding of DC development, and their
      function in orchestrating the innate immune modules. 

PMID- 24874452
TI  - An unconventional bilayer ice structure on a NaCl(001) film.
AB  - Water-solid interactions are of broad importance both in nature and technology.
      The hexagonal bilayer model based on the Bernal-Fowler-Pauling ice rules has been
      widely adopted to describe water structuring at interfaces. Using a cryogenic
      scanning tunnelling microscope, here we report a new type of two-dimensional ice
      like bilayer structure built from cyclic water tetramers on an insulating
      NaCl(001) film, which is completely beyond this conventional bilayer picture. A
      novel bridging mechanism allows the interconnection of water tetramers to form
      chains, flakes and eventually a two-dimensional extended ice bilayer containing a
      regular array of Bjerrum D-type defects. Ab initio density functional theory
      calculations substantiate this bridging growth mode and reveal a striking proton
      disordered ice structure. The formation of the periodic Bjerrum defects with
      unusually high density may have a crucial role as H donor sites in directing
      multilayer ice growth and in catalysing heterogeneous chemical reactions on water
      coated salt surfaces. 

PMID- 24874454
TI  - Longitudinal changes in clock drawing test (CDT) performance before and after
      cognitive decline.
AB  - BACKGROUND: Many scoring systems exist for clock drawing task variants. However,
      none of them are reliable in evaluating longitudinal changes of cognitive
      function. The purpose of this study is to create a simple yet optimal scoring
      procedure to evaluate cognitive decline using a clinic-based sample. METHODS:
      Clock-drawings from 121 participants (76 individuals with no dementia and later
      did not develop dementia after a mean 41.2-month follow-up, 45 individuals with
      no dementia became demented after a mean 42.3-month follow-up) were analyzed
      using t-test to determine a new and simplified CDT scoring system. The new
      scoring method was then compared with other commonly used systems. RESULTS: In
      the converters, there were only 7 items that are significantly different between
      the initial visits and the second visits. We propose a new scoring system that
      includes the seven critical items: numbers are equally spaced (12-3-6-9) (p =
      0.031), the other eight numbers are marked (p = 0.022), numbers are clockwise (p
      = 0.002), all numbers are correct (p = 0.030), distance between numbers is
      constant (p = 0.016), clock has two hands (p = 0.000), arrows are drawn (p =
      0.003). Compared with other traditionally used scoring methods, this based change
      clock drawing test (BCCDT) has one of the most balanced
      sensitivities/specificities with a clinic-based sample. CONCLUSIONS: The new CDT
      scoring system provides further evidence in support of a simple and reliable
      clock-drawing scoring system in follow-up studies to evaluate cognitive decline,
      which can be used in assessing the efficacy of medicine.

PMID- 24874453
TI  - Lower expression of glutamic acid decarboxylase 67 in the prefrontal cortex in
      schizophrenia: contribution of altered regulation by Zif268.
AB  - OBJECTIVE: Cognitive deficits of schizophrenia may be due at least in part to
      lower expression of the 67-kDa isoform of glutamic acid decarboxylase (GAD67), a
      key enzyme for GABA synthesis, in the dorsolateral prefrontal cortex of
      individuals with schizophrenia. However, little is known about the molecular
      regulation of lower cortical GAD67 levels in schizophrenia. The GAD67 promoter
      region contains a conserved Zif268 binding site, and Zif268 activation is
      accompanied by increased GAD67 expression. Thus, altered expression of the
      immediate early gene Zif268 may contribute to lower levels of GAD67 mRNA in the
      dorsolateral prefrontal cortex in schizophrenia. METHOD: The authors used
      polymerase chain reaction to quantify GAD67 and Zif268 mRNA levels in
      dorsolateral prefrontal cortex area 9 from 62 matched pairs of schizophrenia and
      healthy comparison subjects, and in situ hybridization to assess Zif268
      expression at laminar and cellular levels of resolution. The effects of
      potentially confounding variables were assessed in human subjects, and the
      effects of antipsychotic treatments were tested in antipsychotic-exposed monkeys.
      The specificity of the Zif268 findings was assessed by quantifying mRNA levels
      for other immediate early genes. RESULTS: GAD67 and Zif268 mRNA levels were
      significantly lower and were positively correlated in the schizophrenia subjects.
      Both Zif268 mRNA-positive neuron density and Zif268 mRNA levels per neuron were
      significantly lower in the schizophrenia subjects. These findings were robust to
      the effects of the confounding variables examined and differed from other
      immediate early genes. CONCLUSIONS: Deficient Zif268 mRNA expression may
      contribute to lower cortical GAD67 levels in schizophrenia, suggesting a
      potential mechanistic basis for altered cortical GABA synthesis and impaired
      cognition in schizophrenia.

PMID- 24874455
TI  - Imaging atomic-level random walk of a point defect in graphene.
AB  - Deviations from the perfect atomic arrangements in crystals play an important
      role in affecting their properties. Similarly, diffusion of such deviations is
      behind many microstructural changes in solids. However, observation of point
      defect diffusion is hindered both by the difficulties related to direct imaging
      of non-periodic structures and by the timescales involved in the diffusion
      process. Here, instead of imaging thermal diffusion, we stimulate and follow the
      migration of a divacancy through graphene lattice using a scanning transmission
      electron microscope operated at 60 kV. The beam-activated process happens on a
      timescale that allows us to capture a significant part of the structural
      transformations and trajectory of the defect. The low voltage combined with ultra
      high vacuum conditions ensure that the defect remains stable over long image
      sequences, which allows us for the first time to directly follow the diffusion of
      a point defect in a crystalline material. 

PMID- 24874456
TI  - Downregulation of expression of xenobiotic efflux genes is associated with pelvic
      pouch inflammation in ulcerative colitis.
AB  - BACKGROUND: As many as 50% of patients with ulcerative colitis who have undergone
      ileal pouch-anal anastomosis develop de novo inflammation in the ileal pouch
      after surgery. With the use of microarray technology, we investigated what gene
      expression changes occur in the pelvic pouch after surgery for ulcerative colitis
      and how these changes vary by pouch outcome. METHODS: Patients who had undergone
      ileal pouch-anal anastomosis and closure of ileostomy had biopsy specimens from
      the pouch and pre-pouch ileum prospectively collected. The subjects were
      allocated into 4 outcome groups: no pouchitis, pouchitis, Crohn's disease-like
      phenotype, and familial adenomatous polyposis controls. RNA was extracted and
      transcriptomes were analyzed using a genome-wide approach. The statistical
      significance of each gene was assessed, and raw P values were corrected for
      multiple comparisons. RESULTS: The expression levels of 2733 transcripts in the
      pouch were significantly associated with outcome. These genes could be classified
      into 3 categories: regulation of the immune system, modification of the
      extracellular matrix, and xenobiotic activity. Contrary to the first 2
      categories, genes involved in xenobiotic activity, such as ABCB1, had lower
      expression in the pouchitis and Crohn's disease-like groups compared with the no
      pouchitis and familial adenomatous polyposis groups. CONCLUSIONS: Transporters of
      compounds including xenobiotics are downregulated in recurrent disease after
      ileal pouch-anal anastomosis, whereas inflammatory pathways are upregulated.
      These findings corroborate the hypothesis that changes in barrier function could
      contribute to development of intestinal inflammation.

PMID- 24874457
TI  - Accuracy of advanced endoscopy and fecal calprotectin for prediction of relapse
      in ulcerative colitis: a prospective study.
AB  - BACKGROUND: The aim of this study was to determine the accuracy of advanced
      endoscopy for prediction of relapse in ulcerative colitis, in comparison with
      serum and fecal biomarkers. METHODS: Patients with ulcerative colitis with
      sustained clinical remission defined as absence of blood in stool for a minimum
      of 3 months and Mayo endoscopic subscore of 0 were included. High-resolution
      rectosigmoidoscopy was performed at baseline and at the end of study (week 52 or
      relapse), assessing mucosal pit pattern by chromoendoscopy and narrow band
      imaging as well as vascular pattern by narrow band imaging. Histology was
      evaluated at baseline and at the end of the study. Follow-up for 1 year or until
      relapse with clinical evaluations and serum and fecal biomarkers every 3 months
      was established. Relapse was defined as presence of blood in stool and a Mayo
      endoscopic subscore >=1 with histologic confirmation. RESULTS: Seventeen out of
      64 patients (27%) relapsed during the follow-up period. Baseline clinical
      characteristics in patients who relapsed and those who did not were similar.
      Neither pit or vascular pattern nor histology was significantly different between
      relapsers and nonrelapsers. Among serum biomarkers, high platelet count was
      significantly associated with higher relapse rates. Fecal calprotectin was
      predictor of relapse within 3- and 12-month period with high specificity but low
      sensitivity. CONCLUSIONS: Advanced endoscopy and histology do not predict relapse
      over 1-year period in patients with ulcerative colitis. Fecal calprotectin can
      predict relapse in 3- and 12-month period with low accuracy.

PMID- 24874458
TI  - CCL25/CCR9 interactions are not essential for colitis development but are
      required for innate immune cell protection from chronic experimental murine
      colitis.
AB  - BACKGROUND: The chemokine CCL25, and its receptor CCR9, constitute a unique
      chemokine/receptor pair, which regulates trafficking of T lymphocytes to the
      small intestine under physiological conditions and is an attractive target for
      small bowel Crohn's disease drug development. We have previously shown that
      CCL25/CCR9 interactions regulate the recovery from acute dextran sulfate sodium
      induced colonic inflammation. In this study, we explored whether these
      interactions also regulate chronic colitis development in 2 independent murine
      models of experimental colitis. METHODS: Histological flow cytometry and qPCR
      analyses were performed to evaluate the role of CL25 and CCR9 in chronic colonic
      inflammation induced by serial exposures to dextran sulfate sodium salts or by
      adoptive transfer of CD45RB(hi) CD4(+) T cell into lymphopenic mice devoid of
      CCL25/CCR9 interactions. RESULTS: Chronic dextran sulfate sodium exposure results
      in exacerbated colitis in mice deficient for either CCR9 or CCL25 when compared
      with wild-type control mice. Although CCR9-deficient T cells traffic to the colon
      and induce severe colitis similar to wild-type T cells in the CD45RB transfer
      model, naive wild-type T cells induce more severe disease in recipient animals
      devoid of CCL25 expression. CONCLUSIONS: CCL25/CCR9 interactions are required for
      modulating protection against large intestinal inflammation in 2 models of
      chronic colitis. These data may have implications for the potential effects of
      disrupting CCL25/CCR9 interactions in humans in the setting of intestinal
      disorders including inflammatory bowel disease.

PMID- 24874460
TI  - Long-term safety and tolerability of once-daily mesalamine granules in the
      maintenance of remission of ulcerative colitis.
AB  - BACKGROUND: Ulcerative colitis (UC), a chronic, relapsing, and remitting
      inflammatory bowel disease, requires long-term treatment to maintain remission.
      In this study, the long-term safety and tolerability of mesalamine granules (MG)
      therapy was evaluated in the maintenance of UC remission. Previous prospective
      studies evaluating different oral mesalamine formulations have not exceeded a
      duration of 14 months. METHODS: A phase 3, multicenter, 24-month, open-label
      extension study evaluating MG 1.5 g once daily in patients who achieved previous
      remission from mild to moderate UC was performed. Eligible patients had
      successfully participated in 1 of 2 previous 6-month double-blind, placebo
      controlled trials or were new patients in remission. Safety assessments included
      monitoring of adverse events (AEs) and clinical laboratory tests. Risk of UC
      recurrence was assessed by the occurrence of UC-related AEs. RESULTS: Of the 393
      patients enrolled (280 from the double-blind studies; 113 new patients), 388 were
      included in the safety population. The most common AEs included nasopharyngitis
      (13.9%), headache (11.6%), and diarrhea (10.8%), and the incidence of these
      events was generally lower in the MG group versus historical placebo group from
      the double-blind studies. Pancreatic, renal, and hepatic AEs occurred in 23
      patients (5.9%). The risk of UC-related AEs was low and was maintained for 24
      months during the open-label study. CONCLUSIONS: Once-daily MG has a favorable
      safety profile for the maintenance of remission for up to 2 years in patients
      with UC.

PMID- 24874459
TI  - Mode of delivery and risk of inflammatory bowel disease in the offspring:
      systematic review and meta-analysis of observational studies.
AB  - BACKGROUND: The incidence of inflammatory bowel disease (IBD) is increasing
      worldwide; however, pathogenesis is not fully understood. The global cesarean
      section (CS) rate is also rising, and evidence suggests that mode of delivery may
      influence colonization of the offspring gut microbiota, predisposing offspring to
      IBD. This study aimed to investigate the relationship between mode of delivery
      and risk of IBD. METHODS: The electronic databases, Embase, CINAHL, and Medline
      (1948 to present) were searched, reference lists were checked, and no
      restrictions were assigned. Full texts of potentially relevant articles were
      evaluated, and included articles were assessed for quality. Raw data were used to
      calculate unadjusted odds ratios reflecting the risk of developing IBD in those
      delivered by cesarean. A meta-analysis was performed using RevMan 5 software to
      obtain a pooled measure of effect. Sensitivity analyses were performed to
      identify results according to specific study designs. RESULTS: Seven eligible
      studies were included; 4 were retrospective cohort design and 3 were case-control
      studies. The total number of children born by CS in the meta-analysis was 1354,
      and 11,355 were delivered vaginally. The proportion of IBD in the CS group was
      0.249% compared with 0.322% in the vaginal delivery group. The pooled odds ratio
      of developing IBD when delivered by CS was 1.00 (95% confidence interval, 0.75
      1.33). CONCLUSIONS: This analysis observed no significant difference in risk of
      IBD in offspring delivered by CS compared with those born vaginally.

PMID- 24874461
TI  - Hepatobiliary manifestations of inflammatory bowel disease.
AB  - Patients with inflammatory bowel diseases (IBDs) may present with several hepatic
      abnormalities. Some of these liver diseases are benign and only require
      observation, whereas others may cause liver failure and require liver
      transplantation. The aim of this review was to present and summarize the latest
      evidence on the most common liver diseases seen in patients with IBD. These
      manifestations can be divided in to 3 groups: those that are seen in association
      with IBD, those that are due to metabolic and physiologic changes induced by the
      IBD and those that are secondary to the drugs used in the treatment of IBD.
      Primary sclerosing cholangitis is one of the most common hepatobiliary
      manifestations of IBD that is more prevalent in patients with ulcerative colitis.
      There is no approved medical treatment for primary sclerosing cholangitis and
      about 50% of patients will require liver transplantation within 10 to 15 years
      from the time of diagnosis. Among the drugs that are commonly used in the
      treatment of IBD, thiopurines and methotrexate impose the higher risk of
      hepatotoxicity. In most cases, dose adjustment and avoidance of hepatotoxins will
      normalize the liver tests and discontinuation of the drug is required in a
      minority of cases. Reactivation of hepatitis B virus during immunosuppressive
      therapy is a major concern and adequate screening and vaccination is warranted.
      The approach to a patient with IBD who presents with abnormal liver chemistries
      can be challenging not only because 2 or more conditions can co-exist but also
      because management must be individualized.

PMID- 24874462
TI  - Role of emerging Campylobacter species in inflammatory bowel diseases.
AB  - The gut microbiota is a central player in the etiology of inflammatory bowel
      diseases. As such, there is intense scientific interest in elucidating the
      specific group/s of bacteria responsible for driving barrier damage and
      perpetuating the chronic inflammation that results in disease. Because of their
      ability to colonize close to the surface of the host intestinal epithelium,
      mucosa-associated bacteria are considered key players in the initiation and
      development of both Crohn's disease and ulcerative colitis. The leading bacterial
      candidates include adherent and invasive Escherichia coli, Helicobacter,
      Fusobacteria, Mycobacteria, and Campylobacter species. Of these, a member of the
      Campylobacter genus, Campylobacter concisus, has recently emerged as a putative
      player in the pathogenesis of inflammatory bowel diseases. Current research
      indicates that this bacterium possesses extraordinarily diverse pathogenic
      capacities as well as unique genetic and functional signatures that are defined
      by their ability to adhere to and invade host cells, secrete toxins, and the
      presence of a virulence-associated restriction-modification system. These
      characteristics enable the potential classification of C. concisus into distinct
      pathotypes, which we have named adherent and invasive C. concisus and adherent
      and toxinogenic C. concisus. In this review, we evaluate evidence for the role of
      emerging Campylobacter species in the pathogenesis of inflammatory bowel
      diseases.

PMID- 24874463
TI  - Synthesis of a cytotoxic ansamycin hybrid.
AB  - The synthesis of a new ansamycin macrolactam derivative that contains an ansa
      chain based on ansamitocin and an aromatic core related to geldanamycin is
      reported. The selective introduction of the cyclic carbamoyl group at C7 and C9
      relies on a biotransformation using a mutant strain of S. hygroscopicus, the
      geldanamycin producer. The ansamycin hybrid forms atropisomers that differ in
      their antiproliferative activity toward cancer cells. 

PMID- 24874464
TI  - Average absorption cross-section of the human body measured at 1-12 GHz in a
      reverberant chamber: results of a human volunteer study.
AB  - The electromagnetic absorption cross-section (ACS) averaged over polarization and
      angle-of-incidence of 60 ungrounded adult subjects was measured at microwave
      frequencies of 1-12 GHz in a reverberation chamber. Average ACS is important in
      non-ionizing dosimetry and exposure studies, and is closely related to the whole
      body averaged specific absorption rate (WBSAR). The average ACS was measured with
      a statistical uncertainty of less than 3% and high frequency resolution for
      individuals with a range of body shapes and sizes allowing the statistical
      distribution of WBSAR over a real population with individual internal and
      external morphologies to be determined. The average ACS of all subjects was found
      to vary from 0.15 to 0.4 m(2); for an individual subject it falls with frequency
      over 1-6 GHz, and then rises slowly over the 6-12 GHz range in which few other
      studies have been conducted. Average ACS and WBSAR are then used as a surrogate
      for worst-case ACS/WBSAR, in order to study their variability across a real
      population compared to literature results from simulations using numerical
      phantoms with a limited range of anatomies. Correlations with body morphological
      parameters such as height, mass and waist circumference have been investigated:
      the strongest correlation is with body surface area (BSA) at all frequencies
      above 1 GHz, however direct proportionality to BSA is not established until above
      5 GHz. When the average ACS is normalized to the BSA, the resulting absorption
      efficiency shows a negative correlation with the estimated thickness of
      subcutaneous body fat. Surrogate models and statistical analysis of the
      measurement data are presented and compared to similar models from the
      literature. The overall dispersion of measured average WBSAR of the sample of the
      UK population studied is consistent with the dispersion of simulated worst-case
      WBSAR across multiple numerical phantom families. The statistical results
      obtained allow the calibration of human exposure assessments made with particular
      phantoms to a population with a range of individual morphologies. 

PMID- 24874465
TI  - A prospective antibacterial for drug-resistant pathogens: a dual warhead
      amphiphile designed to track interactions and kill pathogenic bacteria by
      membrane damage and cellular DNA cleavage.
AB  - A rationally designed bactericidal amphiphile acts on compelling targets and has
      the potential to disarm resistance development in pathogenic bacteria. 

PMID- 24874466
TI  - Robustness of topological Hall effect of nontrivial spin textures.
AB  - We analyze the topological Hall conductivity (THC) of topologically nontrivial
      spin textures like magnetic vortices and skyrmions and investigate its possible
      application in the readback for magnetic memory based on those spin textures.
      Under adiabatic conditions, such spin textures would theoretically yield
      quantized THC values, which are related to topological invariants such as the
      winding number and polarity, and as such are insensitive to fluctuations and
      smooth deformations. However, in a practical setting, the finite size of spin
      texture elements and the influence of edges may cause them to deviate from their
      ideal configurations. We calculate the degree of robustness of the THC output in
      practical magnetic memories in the presence of edge and finite size effects. 

PMID- 24874467
TI  - Age-related increase in alanine aminotransferase correlates with elevated levels
      of plasma amino acids, decanoylcarnitine, Lp-PLA2 Activity, oxidative stress, and
      arterial stiffness.
AB  - We investigated plasma metabolite profiles that correlated with age-related serum
      alanine aminotransferase (ALT) levels. The study included 602 healthy,
      nondiabetic subjects (aged 30-65 years); 393 individuals had normal ALT levels at
      baseline. Fifty-three (13.5%) individuals developed elevated ALT levels after 3
      years. The remaining 340 subjects with normal ALT were matched to the elevated
      ALT group (n = 53) for age, gender, BMI, fasting glucose, and ALT to form the
      control group (n = 53). At the 3-year follow-up, the elevated-ALT group exhibited
      greater increases in waist circumference, serum free fatty acid, ALT, aspartate
      aminotransferase (AST), gamma-glutamyltransferase (GGT), bilirubin, plasma
      oxidized LDL, Lp-PLA2 activity, urinary 8-epi-prostaglandin F2alpha (8-epi
      PGF2alpha), and brachial-ankle pulse-wave velocity (ba-PWV) compared to the
      control group after baseline adjustment. The elevated-ALT group exhibited greater
      increases in plasma l-valine (q = 0.036), l-leucine (q = 0.012), l-phenylalanine
      (q = 0.012), and decanoylcarnitine (q = 0.002). Mean ALT levels positively
      correlated with changes in these four metabolites, which correlated with changes
      in AST, GGT, Lp-PLA2 activity, urinary 8-epi-PGF2alpha, and ba-PWV. Mean ALT
      changes did not significantly correlate with HOMA-insulin resistance. These
      results suggest that increased plasma levels of l-valine, l-leucine, l
      phenylalanine, and decanoylcarnitine precede insulin resistance during periods of
      elevated ALT. This metabolic disturbance coincides with enhanced risk factors for
      cardiovascular disease. 

PMID- 24874468
TI  - Prognostic awareness and communication of prognostic information in malignant
      glioma: a systematic review.
AB  - Malignant glioma (MG) is a devastating neurological disease with a uniformly poor
      prognosis and a clinical course characterized by progressive functional and
      cognitive impairment. A small body of literature addresses patients' and
      caregivers' prognostic awareness (PA), or understanding of prognosis in patients
      with cancer. Studies that examine PA and desire for prognostic information among
      patients with MG are limited. We sought to review the existing literature on PA
      and communication of prognostic information to patients with MG. Fourteen studies
      examining PA or experience and preferences regarding communication of prognostic
      information were included. The definition and measurement of PA across studies
      varied, and the prevalence of accurate PA ranged from 25 to 100 % of
      participants. There is likely a subset of patients who do not desire accurate
      prognostic information, although the patient and disease characteristics that
      predict this preference are currently unknown. This review suggests that patients
      with MG desire prognostic information communicated in a manner that preserves
      hope. Systematic investigation to define communication needs for prognostic
      information in the unique clinical setting of MG is needed.

PMID- 24874469
TI  - Lower apparent diffusion coefficients indicate distinct prognosis in low-grade
      and high-grade glioma.
AB  - Tumor grade and molecular variants influence the survival of patients with
      glioma. The apparent diffusion coefficient (ADC) map is a non-invasive tool for
      evaluating the outcomes and response to therapy in glioma. In this study, we
      investigated the correlation between the tumor grade and prognostic biomarkers
      with the ADC in glioma patients. Eighty-two patients with supratentorial glioma
      were identified via analysis of surgical specimens and neuroradiological data.
      Using the World Health Organization grade, histological subtype, and molecular
      variants (1p/19q codeletion, isocitrate dehydrogenase 1/2 mutation, Ki-67 index,
      O6-methylguanine DNA methyltransferase, P53, and vascular endothelial growth
      factor immunoactivity) as prognostic biomarkers, we performed receiver operating
      characteristic analysis and multiple linear regression to assess the association
      between the magnetic resonance diffusion parameter and mean ADC and the
      prognostic factors of glioma pathology. Univariate analysis and multiple linear
      regression revealed inverse correlations between the ADC values and the tumor
      grade, oligodendrocytoma histology, and 1p/19q codeletion. A threshold mean ADC
      value could predict the 1p/19q chromosomal status in WHO II gliomas with 72 %
      sensitivity and 88 % specificity (area under the curve 0.82, 95 % confidence
      interval 0.68-0.97) and could distinguish low-grade glioma with low-risk factors
      from the high-risk group (P < 0.01). The mean ADC value could be used as a non
      invasive tool to evaluate the prognosis of supratentorial glioma patients. A
      threshold mean ADC value could be used to predict the 1p/19q codeletion and to
      identify low-risk low-grade gliomas (LGGs). Lower ADC values are indicative of a
      favorable prognosis in LGGs.

PMID- 24874470
TI  - Impact of morphine, fentanyl, oxycodone or codeine on patient consciousness,
      appetite and thirst when used to treat cancer pain.
AB  - BACKGROUND: There is increasing focus on providing high quality care for people
      at the end of life, irrespective of disease or cause, and in all settings. In the
      last ten years the use of care pathways to aid those treating patients at the end
      of life has become common worldwide. The use of the Liverpool Care Pathway in the
      UK has been criticised. In England the LCP was the subject of an independent
      review, commissioned by a Health Minister. The Neuberger Review acknowledged that
      the LCP was based on the sound ethical principles that provide the basis of good
      quality care for patients and families when implemented properly. It also found
      that the LCP often was not implemented properly, and had instead become a barrier
      to good care; it made over 40 recommendations, including education and training,
      research and development, access to specialist palliative care services, and the
      need to ensure care and compassion for all dying patients. In July 2013, the
      Department of Health released a statement that stated the use of the LCP should
      be "phased out over the next 6-12 months and replaced with an individual approach
      to end of life care for each patient".The impact of opioids was a particular
      concern because of their potential influence on consciousness, appetite and
      thirst in people near the end of life. There was concern that impaired patient
      consciousness may lead to an earlier death, and that effects of opioids on
      appetite and thirst may result in unnecessary suffering. This rapid review,
      commissioned by the National Institute for Health Research, used standard
      Cochrane methodology to examine adverse effects of morphine, fentanyl, oxycodone,
      and codeine in cancer pain studies as a close approximation to possible effects
      in the dying patient. OBJECTIVES: To determine the impact of opioid treatment on
      patient consciousness, appetite and thirst in randomised controlled trials of
      morphine, fentanyl, oxycodone or codeine for treating cancer pain. SEARCH
      METHODS: We assessed adverse event data reported in studies included in current
      Cochrane reviews of opioids for cancer pain: specifically morphine, fentanyl,
      oxycodone, and codeine. SELECTION CRITERIA: We included randomised studies using
      multiple doses of four opioid drugs (morphine, fentanyl, oxycodone, and codeine)
      in cancer pain. These were taken from four existing or ongoing Cochrane reviews.
      Participants were adults aged 18 and over. We included only full journal
      publication articles. DATA COLLECTION AND ANALYSIS: Two review authors
      independently extracted adverse event data, and examined issues of study quality.
      The primary outcomes sought were numbers of participants experiencing adverse
      events of reduced consciousness, appetite, and thirst. Secondary outcomes were
      possible surrogate measures of the primary outcomes: delirium, dizziness,
      hallucinations, mood change and somnolence relating to patient consciousness, and
      nausea, vomiting, constipation, diarrhoea, dyspepsia, dysphagia, anorexia,
      asthenia, dehydration, or dry mouth relating to appetite or thirst.Comparative
      measures of harm were known to be unlikely, and we therefore calculated the
      proportion of participants experiencing each of the adverse events of interest
      with each opioid, and for all four opioid drugs combined. MAIN RESULTS: We
      included 77 studies with 5619 randomised participants. There was potential bias
      in most studies, with small size being the most common; individual treatment
      groups had fewer than 50 participants in 60 studies. Participants were relatively
      young, with mean age in the studies typically between 50 and 70 years. Multiple
      major problems with adverse event reporting were found, including failing to
      report adverse events in all participants who received medication, all adverse
      events experienced, how adverse events were collected, and not defining adverse
      event terminology or whether a reporting system was used.Direct measures of
      patient consciousness, patient appetite, or thirst were not apparent. For opioids
      used to treat cancer pain adverse event incidence rates were 25% for
      constipation, 23% for somnolence, 21% for nausea, 17% for dry mouth, and 13% for
      vomiting, anorexia, and dizziness. Asthenia, diarrhoea, insomnia, mood change,
      hallucinations and dehydration occurred at incidence rates of 5% and below.
      AUTHORS' CONCLUSIONS: We found no direct evidence that opioids affected patient
      consciousness, appetite or thirst when used to treat cancer pain. However,
      somnolence, dry mouth, and anorexia were common adverse events in people with
      cancer pain treated with morphine, fentanyl, oxycodone, or codeine.We are aware
      that there is an important literature concerning the problems that exist with
      adverse event measurement, reporting, and attribution. Together with the known
      complications concerning concomitant medication, data collection and reporting,
      and nomenclature, this means that these adverse events cannot always be
      attributed unequivocally to the use of opioids, and so they provide only a broad
      picture of adverse events with opioids in cancer pain. The research agenda
      includes developing definitions for adverse events that have a spectrum of
      severity or importance, and the development of appropriate measurement tools for
      recording such events to aid clinical practice and clinical research.

PMID- 24874471
TI  - Identification of druggable cancer driver genes amplified across TCGA datasets.
AB  - The Cancer Genome Atlas (TCGA) projects have advanced our understanding of the
      driver mutations, genetic backgrounds, and key pathways activated across cancer
      types. Analysis of TCGA datasets have mostly focused on somatic mutations and
      translocations, with less emphasis placed on gene amplifications. Here we
      describe a bioinformatics screening strategy to identify putative cancer driver
      genes amplified across TCGA datasets. We carried out GISTIC2 analysis of TCGA
      datasets spanning 16 cancer subtypes and identified 486 genes that were amplified
      in two or more datasets. The list was narrowed to 75 cancer-associated genes with
      potential "druggable" properties. The majority of the genes were localized to 14
      amplicons spread across the genome. To identify potential cancer driver genes, we
      analyzed gene copy number and mRNA expression data from individual patient
      samples and identified 42 putative cancer driver genes linked to diverse
      oncogenic processes. Oncogenic activity was further validated by siRNA/shRNA
      knockdown and by referencing the Project Achilles datasets. The amplified genes
      represented a number of gene families, including epigenetic regulators, cell
      cycle-associated genes, DNA damage response/repair genes, metabolic regulators,
      and genes linked to the Wnt, Notch, Hedgehog, JAK/STAT, NF-KB and MAPK signaling
      pathways. Among the 42 putative driver genes were known driver genes, such as
      EGFR, ERBB2 and PIK3CA. Wild-type KRAS was amplified in several cancer types, and
      KRAS-amplified cancer cell lines were most sensitive to KRAS shRNA, suggesting
      that KRAS amplification was an independent oncogenic event. A number of MAP
      kinase adapters were co-amplified with their receptor tyrosine kinases, such as
      the FGFR adapter FRS2 and the EGFR family adapters GRB2 and GRB7. The ubiquitin
      like ligase DCUN1D1 and the histone methyltransferase NSD3 were also identified
      as novel putative cancer driver genes. We discuss the patient tailoring
      implications for existing cancer drug targets and we further discuss potential
      novel opportunities for drug discovery efforts. 

PMID- 24874473
TI  - A novel decoy receptor fusion protein for FGF-2 potently inhibits tumour growth.
AB  - BACKGROUND: Antiangiogenic therapies have been proven effective in cancer
      treatment. Fibroblast growth factor-2 (FGF-2) has been functionally implicated in
      tumour angiogenesis and is an important target of antiangiogenic therapies. The
      aim of this work was to develop a novel FGF-2 inhibitor for cancer therapy.
      METHODS: Eleven fusion proteins were developed by fusing various truncated
      extracellular regions of FGFR1 with the Fc region of IgG1. The optimal decoy
      receptor fusion protein with the highest binding affinity for FGF-2 was
      identified by an FGF-2-binding assay and its potential antitumour effects were
      investigated. RESULTS: We obtained a soluble decoy receptor fusion protein with
      the highest binding activity for FGF-2, named FGF-Trap. Fibroblast growth factor
      Trap significantly abolished FGF-2-stimulated activation of FGF signalling as
      demonstrated by its suppression of FGF-2-mediated phosphorylation of Erk1/2 and
      Akt, upregulation of cyclins D1 and E and the increase in mRNA levels of vascular
      endothelial growth factor R1 and R2 (VEGFR1 and VEGFR2). Furthermore, FGF-Trap
      effectively suppressed FGF-2-induced proliferation and migration of human
      umbilical vein endothelial cells (HUVECs) in vitro. Most importantly, FGF-Trap
      potently inhibited tumour growth and angiogenesis in Caki-1 and A549 xenograft
      models in vivo. CONCLUSIONS: Fibroblast growth factor-Trap potently inhibits
      tumour growth by blocking FGF-2 signalling pathways and could be an effective
      therapeutic agent for cancer patients.

PMID- 24874474
TI  - AEG-1 expression is an independent prognostic factor in rectal cancer patients
      with preoperative radiotherapy: a study in a Swedish clinical trial.
AB  - BACKGROUND: Preoperative radiotherapy (RT) is widely used to downstage rectal
      tumours, but the rate of recurrence varies significantly. Therefore, new
      biomarkers are needed for better treatment and prognosis. It has been shown that
      astrocyte elevated gene-1 (AEG-1) is a key mediator of migration, invasion, and
      treatment resistance. Our aim was to analyse the AEG-1 expression in relation to
      RT in rectal cancer patients and to test its radiosensitising properties.
      METHODS: The AEG-1 expression was examined by immunohistochemistry in 158
      patients from the Swedish clinical trial of RT. Furthermore, we inhibited the AEG
      1 expression by siRNA in five colon cancer cell lines and measured the survival
      after irradiation by colony-forming assay. RESULTS: The AEG-1 expression was
      increased in the primary tumours compared with the normal mucosa independently of
      the RT (P<0.01). High AEG-1 expression in the primary tumour of the patients
      treated with RT correlated independently with higher risk of distant recurrence
      (P=0.009) and worse disease-free survival (P=0.007). Downregulation of AEG-1
      revealed a decreased survival after radiation in radioresistant colon cancer cell
      lines. CONCLUSIONS: The AEG-1 expression was independently related to distant
      recurrence and disease-free survival in rectal cancer patients with RT and could
      therefore be a marker to discriminate patients for distant relapse.

PMID- 24874475
TI  - CD10 as a novel marker of therapeutic resistance and cancer stem cells in head
      and neck squamous cell carcinoma.
AB  - BACKGROUND: Cancer stem cells (CSCs) are responsible for treatment failure.
      However, their identification and roles in resistance are not well established in
      head and neck squamous cell carcinoma (HNSCC). METHODS: Three HNSCC cell lines
      (FaDu, Detroit562 and BICR6) were treated with cisplatin or radiation. Cell
      surface antigens were analysed by LyoPlate, a novel cell surface antigen array.
      The expression levels of antigens highly expressed after treatments were further
      compared between cisplatin-resistant Detroit562 cells and its parental line.
      Association of the candidate antigen with CSCs properties, namely sphere
      formation and in vivo tumourigenicity, was also examined. RESULTS: CD10, CD15s,
      CD146 and CD282 were upregulated across the treated cell lines, while the
      increased expression of CD10 was prominent in the cisplatin-resistant cell line.
      Isolation mediated by FACS revealed that the CD10-positive subpopulation was more
      refractory to cisplatin, fluorouracil and radiation than the CD10-negative
      subpopulation. It also showed an increased ability to form spheres in vitro and
      tumours in vivo. Moreover, the CD10-positive subpopulation expressed the CSC
      marker OCT3/4 at a higher level than that in the CD10-negative subpopulation.
      CONCLUSIONS: CD10 is associated with therapeutic resistance and CSC-like
      properties of HNSCC. CD10 may serve as a target molecule in the treatment of
      refractory HNSCC.

PMID- 24874476
TI  - Epidemiology of basal cell carcinoma in the United Kingdom: incidence, lifestyle
      factors, and comorbidities.
AB  - BACKGROUND: Little is known about the epidemiology of basal cell carcinoma (BCC).
      METHODS: Using the Clinical Practice Research Datalink, we calculated annual
      incidence rates. In a case-control analysis, we examined lifestyle factors and
      comorbidities. RESULTS: Incidence rose significantly between 2000 and 2011. Basal
      cell carcinoma risk was increased in alcohol drinkers (slightly) and
      immunocompromised patients, but reduced in smokers and individuals with abnormal
      weight. CONCLUSIONS: Basal cell carcinoma places a growing public health burden.
      Lifestyle factors do not play a major role in pathogenesis, but immunosuppression
      is important.

PMID- 24874477
TI  - Elastin peptides regulate HT-1080 fibrosarcoma cell migration and invasion
      through an Hsp90-dependent mechanism.
AB  - BACKGROUND: The elastin-derived peptides (EDPs) exert protumoural activities by
      potentiating the secretion of matrix metalloproteinases (MMP) and the plasminogen
      plasmin activating system. In the present paper, we studied heat-shock protein 90
      (Hsp90) involvement in this mechanism. METHODS: HT-1080 fibrosarcoma cell
      migration and invasion were studied in artificial wound assay and modified Boyden
      chamber assay, respectively. Heat-shock protein 90 was studied by western blot
      and immunofluorescence. Matrix metalloproteinase-2 and urokinase plasminogen
      activator (uPA) were studied by gelatin +/- plasminogen zymography and
      immunofluorescence. Heat-shock protein 90 partners were studied by
      immunoprecipitation. Messenger RNA expression was studied using real-time PCR.
      Small interfering RNAs were used to confirm the essential role of Hsp90. RESULTS:
      We showed that kappa-elastin and VGVAPG elastin hexapeptide stimulated Hsp90, pro
      MMP-2 and uPA secretion within 6 h, whereas AGVPGLGVG and GRKRK peptides had no
      effect. No increase of mRNA level was observed. Heat-shock protein 90-specific
      inhibitors inhibit EDP-stimulated HT-1080 cell-invasive capacity and restrained
      EDP-stimulated pro-MMP-2 and uPA secretions. The inhibitory effect was reproduced
      by using Hsp90-blocking antibody or Hsp90 knockdown by siRNA. Heat-shock protein
      90 interacted with and stabilised uPA and pro-MMP-2 in conditioned culture media
      of HT-1080 fibrosarcoma cells. CONCLUSIONS: Taken together, our results
      demonstrate that EDPs exert protumoural activities through an Hsp90-dependent
      mechanism involving pro-MMP-2 and uPA.

PMID- 24874478
TI  - C-reactive protein level is a prognostic indicator for survival and improves the
      predictive ability of the R-IPI score in diffuse large B-cell lymphoma patients.
AB  - BACKGROUND: High levels of C-reactive protein (CRP), an acute phase protein,
      proofed being associated with decreased clinical outcome in small-scale studies
      in diffuse large B-cell lymphoma (DLBCL). The aim of this study was to evaluate
      the prognostic impact of pretreatment CRP levels on overall survival (OS) and
      disease-free survival (DFS) in a large bicentre study of DLBCL patients. METHODS:
      Data from 477 DLBCL patients, diagnosed and treated between 2004 and 2013 at two
      Austrian centres, were evaluated retrospectively. The prognostic influence of CRP
      and other factors, including age, tumour stage, and revised International
      Prognostic Index (R-IPI) on 5-year OS and 5-year DFS, were studied by Kaplan
      Meier curves as well as univariate and multivariate Cox regression models.
      Influence of CRP on the predictive accuracy of the R-IPI score was determined by
      the Harrell concordance index. RESULTS: Kaplan-Meier curves revealed elevated CRP
      as a factor for decreased 5-year OS and DFS in DLBCL patients (P<0.001, log-rank
      test). An independent significant association between high CRP levels and poor
      clinical outcome in multivariate analysis for 5-year OS (HR=1.51, CI 95%=1.04
      2.20, P=0.031) and for DFS (HR=1.91, CI 95%=1.28-2.85, P=0.002) was found. The
      estimated concordance index was 0.75 using the original R-IPI score and 0.79 when
      CRP was added. CONCLUSIONS: In the present study, we demonstrated high CRP levels
      at diagnosis of DLBCL as an independent poor prognostic factor for clinical
      outcome. Adding CRP to the well-established prognostic models such as the R-IPI
      score might improve their predictive ability.

PMID- 24874479
TI  - Genetic ablation of beta-catenin inhibits the proliferative phenotype of mouse
      liver adenomas.
AB  - BACKGROUND: Aberrant activation of Wnt/beta-catenin has been implicated in
      various cancer-related processes, for example, proliferation or tumour cell
      survival. However, the exact mechanism by which beta-catenin provides liver
      tumour cells with a selective advantage is still unclear. This study was aimed to
      analyse growth behaviour and survival of beta-catenin-driven mouse liver tumours
      after beta-catenin ablation. METHODS: Transgenic mice with a controllable
      hepatocyte-specific knockout of Ctnnb1 (encoding beta-catenin) were generated and
      liver tumours were induced by means of a N-nitrosodiethylamine/phenobarbital
      tumour initiation/promotion protocol, which leads to the outgrowth of
      hepatocellular tumours with activated beta-catenin. Cre recombinase was activated
      and the effects of the knockout in the tumours were studied. RESULTS: Activation
      of Cre recombinase led to the knockout of Ctnnb1 in a fraction of tumour cells,
      thus resulting in the formation of two different tumour cell subpopulations, with
      or without beta-catenin. Comparative analysis of the two subpopulations revealed
      that cell proliferation was significantly decreased in Ctnnb1-deleted hepatoma
      cells, compared with the corresponding non-deleted cell population, whereas no
      increased rate of apoptosis after knockout of Ctnnb1 was observed. CONCLUSIONS:
      beta-catenin-dependent signalling is an important regulator of hepatoma cell
      growth in mice, but not a crucial factor in the regulation of tumour survival.

PMID- 24874480
TI  - The relationship between the tumour stroma percentage, clinicopathological
      characteristics and outcome in patients with operable ductal breast cancer.
AB  - BACKGROUND: The percentage of tumour stroma (TSP) has recently been reported to
      be a novel independent predictor of outcome in patients with a variety of common
      solid organ tumours. The aim of this study was to examine the relationship
      between TSP, clinicopathological characteristics and outcome in patients with
      invasive ductal breast cancer, in particular node negative and triple negative
      disease. METHODS: A total of 361 patients with primary operable invasive ductal
      breast cancer were included in this study. The TSP was assessed visually on the
      haematoxylin and eosin-stained tissue sections. With a cutoff value of 50% TSP,
      patients with <= 50% stroma were classified as the low-TSP group and those with
      >50% stroma were classified as the high-TSP group. RESULTS: A total of 109 (30%)
      patients had high TSP. Patients with high TSP were old age (P=0.035), had more
      Her-2-positive tumours (P=0.029), low-grade tumour inflammatory infiltrate
      (P=0.034), low CD68+macrophage infiltrate (P<0.001), low CD4+ (P=0.023) and low
      CD8+ T-lymphocytes infiltrate (P=0.017), tumour recurrence (P=0.015) and shorter
      cancer-specific survival (P<0.001). In node-negative patients (n=207), high TSP
      was associated with low CD68+macrophage infiltrate (P=0.001), low CD4+ (P=0.040)
      and low CD8+ T-lymphocytes infiltrate (P=0.016) and shorter cancer-specific
      survival (P=0.005). In triple negative patients (n=151), high TSP was associated
      with high tumour grade (P=<0.001), lymph node positivity (P=0.027), low
      CD68+macrophage infiltrate (P=0.011) and shorter cancer-specific survival
      (P=0.035). The 15-year cancer-specific survival rate was 79% vs 21% in the low
      TSP group vs high-TSP group. In multivariate survival analysis, a high TSP was
      associated with reduced cancer-specific survival in the whole cohort (P=0.001),
      node-negative patients (P=0.007) and those who received systemic adjuvant therapy
      (P=0.021), independent of other pathological characteristics including host
      inflammatory response. However, TSP was not an independent prognostic factor for
      triple negative patients (P=0.151). CONCLUSIONS: A high TSP in primary operable
      invasive ductal breast cancer was associated with recurrence and poorer long-term
      survival. The inverse relation with the tumour inflammatory infiltrate highlights
      the importance of the amount of tumour stroma on immunological response in
      patients with primary operable ductal breast cancer. Implementing this simple and
      reproducible parameter in routine pathological examination may help optimise risk
      stratification in patients with invasive ductal breast cancer.

PMID- 24874481
TI  - TBLR1 is a novel prognostic marker and promotes epithelial-mesenchymal transition
      in cervical cancer.
AB  - BACKGROUND: Invasion and metastasis remain a critical issue in cervical cancer.
      However, the underlying mechanism of it in cervical cancer remains unclear. The
      newly discovered protein, TBLR1, plays a crucial role in regulating various key
      cellular functions. METHODS: In this study, western blot, real-time RT-PCR,
      immunohistochemical staining, 3D morphogenesis Matrigel culture, wound healing
      and Boyden chamber invasion assays, xenografted tumour model, luciferase assays,
      and chromatin immunoprecipitation assays were used. RESULTS: The expression of
      TBLR1 in cervical cancer cell lines and tissues was significantly upregulated at
      both the RNA and protein levels compared with that in normal cervical cells.
      Statistical analysis suggested that TBLR1 as an independent prognostic factor was
      significantly correlated with the clinical stage, survival time and recurrence.
      Moreover, overexpression of TBLR1 in Hela and Siha cell lines promoted invasion
      in vitro and in vivo with the increases of the mesenchymal factors vimentin and
      fibronectin and decreases of the epithelial marker alpha-catenin. In contrast,
      RNAi-mediated knockdown of TBLR1 inhibited epithelial-mesenchymal transition in
      vitro and in vivo. Further study indicated that this might be mediated via the NF
      kappaB and Wnt/beta-Catenin signalling pathway, and involve regulation of Snail
      and Twist. CONCLUSIONS: The TBLR1 protein may be a prognostic marker in cervical
      cancer and play an important role in the invasion and metastasis of human
      cervical cancer.

PMID- 24874486
TI  - Renormalized coupled cluster approaches in the cluster-in-molecule framework:
      predicting vertical electron binding energies of the anionic water clusters
      (H2O)(n)(-).
AB  - Anionic water clusters are generally considered to be extremely challenging to
      model using fragmentation approaches due to the diffuse nature of the excess
      electron distribution. The local correlation coupled cluster (CC) framework
      cluster-in-molecule (CIM) approach combined with the completely renormalized CR
      CC(2,3) method [abbreviated CIM/CR-CC(2,3)] is shown to be a viable alternative
      for computing the vertical electron binding energies (VEBE). CIM/CR-CC(2,3) with
      the threshold parameter zeta set to 0.001, as a trade-off between accuracy and
      computational cost, demonstrates the reliability of predicting the VEBE, with an
      average percentage error of ~15% compared to the full ab initio calculation at
      the same level of theory. The errors are predominantly from the electron
      correlation energy. The CIM/CR-CC(2,3) approach provides the ease of a black-box
      type calculation with few threshold parameters to manipulate. The cluster sizes
      that can be studied by high-level ab initio methods are significantly increased
      in comparison with full CC calculations. Therefore, the VEBE computed by the
      CIM/CR-CC(2,3) method can be used as benchmarks for testing model potential
      approaches in small-to-intermediate-sized water clusters. 

PMID- 24874485
TI  - Situs inversus totalis associated with a tumor in the cecum.

PMID- 24874483
TI  - COX-2 expression is predictive for early relapse and aromatase inhibitor
      resistance in patients with ductal carcinoma in situ of the breast, and is a
      target for treatment.
AB  - BACKGROUND: Stratification of patients for treatment of ductal carcinoma in situ
      (DCIS) is suboptimal, with high systemic overtreatment rates. METHODS: A training
      set of 95 tumours from women with pure DCIS were immunostained for proteins
      involved in cell survival, hypoxia, growth factor and hormone signalling. A
      generalised linear regression with regularisation and variable selection was
      applied to a multiple covariate Cox survival analysis with recurrence-free
      survival 10-fold cross-validation and leave-one-out iterative approach were used
      to build and test the model that was validated using an independent cohort of 58
      patients with pure DCIS. The clinical role of a COX-2-targeting agent was then
      tested in a proof-of-concept neoadjuvant randomised trial in ER-positive DCIS
      treated with exemestane 25 mg day(-1)+/- celecoxib 800 mg day(-1). RESULTS: The
      COX-2 expression was an independent prognostic factor for early relapse in the
      training (HR 37.47 (95% CI: 5.56-252.74) P=0.0001) and independent validation
      cohort (HR 3.9 (95% CI: 1.8-8.3) P=0.002). There was no significant interaction
      with other clinicopathological variables. A statistically significant reduction
      of Ki-67 expression after treatment with exemestane +/- celecoxib was observed
      (P<0.02) with greater reduction in the combination arm (P<0.004). Concomitant
      reduction in COX-2 expression was statistically significant in the exemestane and
      celecoxib arm (P<0.03) only. CONCLUSIONS: In patients with DCIS, COX-2 may
      predict recurrence, aiding clinical decision making. A combination of an
      aromatase inhibitor and celecoxib has significant biological effect and may be
      integrated into treatment of COX2-positive DCIS at high risk of recurrence.

PMID- 24874482
TI  - Molecular targets of aspirin and cancer prevention.
AB  - Salicylates from plant sources have been used for centuries by different cultures
      to treat a variety of ailments such as inflammation, fever and pain. A chemical
      derivative of salicylic acid, aspirin, was synthesised and mass produced by the
      end of the 19th century and is one of the most widely used drugs in the world.
      Its cardioprotective properties are well established; however, recent evidence
      shows that it can also act as a chemopreventive agent. Its antithrombotic and
      anti-inflammatory actions occur through the inhibition of cyclooxygenases. The
      precise mechanisms leading to its anticancer effects are not clearly established,
      although multiple mechanisms affecting enzyme activity, transcription factors,
      cellular signalling and mitochondrial functions have been proposed. This review
      presents a brief account of the major COX-dependent and independent pathways
      described in connection with aspirin's anticancer effects. Aspirin's unique
      ability to acetylate biomolecules besides COX has not been thoroughly
      investigated nor have all the targets of its primary metabolite, salicylic acid
      been identified. Recent reports on the ability of aspirin to acetylate multiple
      cellular proteins warrant a comprehensive study to investigate the role of this
      posttranslational modification in its anticancer effects. In this review, we also
      raise the intriguing possibility that aspirin may interact and acetylate cellular
      molecules such as RNA, and metabolites such as CoA, leading to a change in their
      function. Research in this area will provide a greater understanding of the
      mechanisms of action of this drug. 

PMID- 24874484
TI  - Gemcitabine diphosphate choline is a major metabolite linked to the Kennedy
      pathway in pancreatic cancer models in vivo.
AB  - BACKGROUND: The modest benefits of gemcitabine (dFdC) therapy in patients with
      pancreatic ductal adenocarcinoma (PDAC) are well documented, with drug delivery
      and metabolic lability cited as important contributing factors. We have used a
      mouse model of PDAC: KRAS(G12D); p53(R172H); pdx-Cre (KPC) that recapitulates the
      human disease to study dFdC intra-tumoural metabolism. METHODS: LC-MS/MS and NMR
      were used to measure drug and physiological analytes. Cytotoxicity was assessed
      by the Sulphorhodamine B assay. RESULTS: In KPC tumour tissue, we identified a
      new, Kennedy pathway-linked dFdC metabolite (gemcitabine diphosphate choline
      (GdPC)) present at equimolar amounts to its precursor, the accepted active
      metabolite gemcitabine triphosphate (dFdCTP). Utilising additional subcutaneous
      PDAC tumour models, we demonstrated an inverse correlation between GdPC/dFdCTP
      ratios and cytidine triphosphate (CTP). In tumour homogenates in vitro, CTP
      inhibited GdPC formation from dFdCTP, indicating competition between CTP and
      dFdCTP for CTP:phosphocholine cytidylyltransferase (CCT). As the structure of
      GdPC precludes entry into cells, potential cytotoxicity was assessed by
      stimulating CCT activity using linoleate in KPC cells in vitro, leading to
      increased GdPC concentration and synergistic growth inhibition after dFdC
      addition. CONCLUSIONS: GdPC is an important element of the intra-tumoural dFdC
      metabolic pathway in vivo.

PMID- 24874487
TI  - Fine structure of the cells containing large granular vesicles in the superior
      cervical ganglia of rat embryos.
AB  - An electron microscopic study has been performed on the superior cervical ganglia
      of 11- to 21-day-old rat embryos after fixation with glutaraldehyde and osmium
      tetroxide. The ganglia of 11-day-old and older embryos are known to consist of
      cells which show catecholamine fluorescence, the intensity of which varies from
      weak to bright. Electron microscopically, the ganglia of 11- and 12-day-old
      embryos were observed to consist of a dense group of cells among the loose
      mesenchyme. The cells showed a great variation in nuclear morphology and only
      rarely contained granular vesicles. Only few cells represented the
      undifferentiated, primitive sympathetic cell type described in previous studies.
      Therefore, in the rat superior cervical ganglion the ultrastuctural
      differentiation may be initiated even before the cells complete their migration.
      From embryonic day 14, three types of cell containing varying numbers of large
      granular vesicles were distinguished on the basis of nuclear morphology. Those
      type 1 cells that contained numerous granular vesicles closely resemble the
      postnatal SIF cells. Those type 2 cells that possessed a great number of granular
      vesicles may represent an intermediate form, namely the large intensely
      fluorescent cell described in prenatal ganglia but only exceptionally found in
      early postnatal ganglia. The appearance of the type 2 cells with only a few
      granular vesicles is identical with that of the sympathetic cells representing
      the early stages of maturation. The type 3 cells correspond with the late
      maturing principal neuron. These cells were never seen to contain more than a few
      large granular vesicles. 

PMID- 24874488
TI  - Phenylethanolamine-N-methyltransferase-immunoreactive cells in developing rat
      superior cervical ganglion and the effect of hydrocortisone on their number.
AB  - Rats were subcutaneously injected with hydrocortisone acetate. Control rats were
      similarly injected with saline. PNMT-immunoreactive cells in the superior
      cervical ganglia were immunohistochemically demonstrated, and the cell densities
      (number/mm(3)) of the PNMT-immunoreactive cells were counted. PNMT-immunoreactive
      cells were detected in ganglia of all age groups of the saline-treated control
      rats. With increasing age, there was a tendency to cluster formation. The number
      of the PNMT immunoreactive cells dramatically increased if hydrocortisone
      administration was initiated during the first two postnatal weeks. Hydrocortisone
      also caused appearance of numerous PNMT-immunoreactive fibres, which were not
      seen in controls. The cell density of the PNMT-immunoreactive cells in the
      hydrocortisone-treated rats was still increased, although less, if the
      hydrocortisone injections were started during the third postnatal week, as
      compared with the saline-injected control rats of the same age. After
      discontinuation of the first, early postnatal hydrocortisone treatment on days 2
      6, the number of the PNMT-immunoreactive cells decreased during the following 2
      weeks, but a second treatment with hydrocortisone daily for 7 days initiated as
      late as on postnatal day 63 caused a new significant increase in cell density and
      the appearance of immunoreactive fibres from them. It is concluded that PNMT
      immunoreactive cells are present in the normal rat superior cervical ganglion
      during the whole postnatal developmental period. Their number can be increased
      with hydro-cortisone, as assessed on the basis of counted cell densities, during
      the first three postnatal weeks. Early postnatal hydrocortisone treatment
      preserves some cells in a stage in which they, on second exposure to
      glucocorticoids, can express PNMT immunoreactivity and increase in cell density. 

PMID- 24874490
TI  - A culture model for age-related human neurofibrillary pathology.
AB  - Cloned human neuroblastoma cells have been induced to differentiate with retinoic
      acid whereupon they form an extensive network of processes and pseudoganglia.
      Ultrastructural examination shows these processes often contain assembled
      neurofilaments arranged parallel to microtubules in orderly arrangements
      characteristic of normal neurons. Perturbation of these differentiated, ganglion
      like cells with agents such as aluminum, zinc, and possibly leupeptin results in
      apparent neurofibrillary pathologies as evidenced by neurofilament specific
      immunofluorescent microscopy. A quantitative increase in neurofilament-specific
      antibody binding induced by aluminum and leupeptin were verified by flow
      cytometry with a fluorescence activated cell sorter. The utility of this system
      in screening agents for their capacity to produce neurofibrillary lesions
      characteristic of age-related human disorders is discussed. 

PMID- 24874489
TI  - The effect of cortisol on gamma-glutamyl transpeptidase activity in the glycogen
      body and lumbosacral segments of developing chick spinal cord.
AB  - Gamma-glutamyl transpeptidase (GGT) activity is heterogeneously distributed
      between the lumbosacral chick spinal cord and the adjacent glycogen body during
      late embryonic and early posthatch development and displays hormonal sensitivity.
      As GGT activity may reflect the cellular transport of some amino acids, the
      transiently high activity of this enzyme in the glycogen body suggests that these
      cells play an important role in amino acid transport and metabolism at a time
      coincident with the initial phase of myelination in the embryonic chick spinal
      cord. 

PMID- 24874491
TI  - Delayed development of GFA immunoreactivity in intraocular cortex cerebri grafts
      during thyroid hormone deficiency.
AB  - Dependency of astrocytes on thyroid hormones during development was studied in
      intraocular cortex cerebri grafts, using antibodies to the glial fibrillary
      acidic protein (GFA). Fetal cortex cerebri was left in the anterior eye chamber
      of normal and thyroidectomized adult recipient rats 3 and 8 weeks to mature. All
      cortex grafts survived and became vascularized in the eye. The grafts were
      cryostat-sectioned, and reacted with an antiserum specific for GFA. The density
      of GFA immunoreactivity in the cortex graft neuropil was subjectively estimated
      with fluorescence microscopy. After 3 weeks in oculo, the number of positive
      structures was significantly lower in the thyroidectomized group as compared to
      the euthyroid control group. This effect of thyroidectomy on the cortex grafts
      was entirely counteracted by daily injections of thyroxine (100 MUg/kg s.c.) to
      similarly thyroidectomized recipients. The distribution of GFA-positive
      structures was even within individual grafts of all three groups. Neither were
      any differences in morphology of fluorescent astroglial processes observed. The
      overall density of fluorescent GFA-positive structures was considerably higher
      than that found in age-matched normal in situ counterparts, even in the
      thyroidectomized group. After 8 weeks in oculo, the difference between the
      control and thyroidectomized groups in density of GFA-positive structures in the
      neuropil had disappeared, and no general increase in density of immunoreactivity
      was noted in the control group. These results indicate that thyroid hormones
      might normally play a role for the development of GFA in the early postnatal
      brain, as thyroid hormone deficiency causes a transient delay in development of
      GFA immunoreactivity in intraocular cortex cerebri grafts. 

PMID- 24874492
TI  - Topological correlation between the cell-recognition protein, R-cognin and alpha
      bungarotoxin receptor in retinal plasma membrane.
AB  - The amount of the neural retina cell recognition protein, R-cognin, in the plasma
      membrane of chick embryo neural retina cells declined 43% between 10 and 17 days
      of embryonic development. Over this period there was a 27% increase in the plasma
      membrane content of the alpha-bungarotoxin receptor. Plasma membranes of both
      these ages were sonicated into vesicles and these vesicles partitioned on alpha
      bungarotoxin agarose beads into those which contained detectable alpha
      bungarotoxin receptor and those which did not. At 10 days, approximately 6% of
      the plasma membrane vesicles contained receptor. At 17 days, <2% did. At 10 days,
      60% of the R-cognin was found in the alpha-bungarotoxin receptor-containing
      vesicles, at 17 days 86%. At 17 days, 6% of the retina membrane with a high
      concentration of both alpha-bungarotoxin receptor and R-cognin was of a density
      indicative of it being of synaptic origin. These results suggested that R-cognin
      and alpha-bungarotoxin receptor occurred close together in the plasma membrane of
      retina cells. However, the lack of competition between R-cognin gamma globulin
      and specific alpha-bungarotoxin binding indicated that the alpha-bungarotoxin
      receptor and R-cognin were not the same protein. Thus, R-cognin and the alpha
      bungarotoxin receptor appear to be separate proteins which occur in close
      proximity on the retina plasma membrane. 

PMID- 24874493
TI  - Effects of ischemia on free fatty acids and diacylglycerols in developing rat
      brain.
AB  - Post-decapitative ischemic treatment imposed on the developing rat brain elicited
      a marked increase in its susceptibility to free fatty acid (FFA) release between
      14 and 17 days, an observation similar to that reported by Bazan (Acta Physiol.
      Lat. Am.21, 15, 1971). Although the level of diacylglycerols (DG) also increased
      during this period, the extent of the increase was not as obvious as the FFA.
      Ischemic treatment to rats after 17 days of age elicited increases in DG and FFA
      enriched in stearic and arachidonic acids. The delayed response in susceptibility
      of brain tissue to ischemia-induced changes seems to suggest that the biochemical
      mechanism(s) responsible for the FFA and DG release is better correlated to
      events commensurating with synaptogenesis than with myelination. 

PMID- 24874494
TI  - Development of mouse spinal cord in tissue culture-III. Quantification of neuron
      development in neural tube microfragment cultures.
AB  - Mouse neural tube development in vitro was examined following the isolation and
      culturing of specific regions of the neural tube. Developmental characteristics
      of neuron formation and differentiation were assessed both quantitatively and
      qualitatively. A 1 mm length of embryonic day 10 mouse neural tube was cut into
      32 microfragments of equal size and cultured on collagen coated cover-slips.
      Neuronal cells were observed to emerge after 3 days in culture and to migrate
      away from the fragment upon an immature astroglial precursor cell layer that had
      begun to form within the first 24 h of culturing. The extent of neuronal
      migration, the density and total number of neurons per outgrowth zone, and the
      size distribution of neurons was quantitated after 21 days in culture. Three
      distinct patterns of neuronal outgrowth (Types II, III and IV) could be observed
      with a fourth pattern (Type I) best described as being neuron free. Neuron free
      outgrowth zones (Type 1) were comprized totally of glial cells and represented
      approximately 10% of the outgrowth zones examined. Characteristics of Type II
      outgrowth zones were a relatively restricted neuronal migration and a
      predominance (85%) of small neurons (< 10MUm diameter) scattered around the
      outgrowth zone. In contrast the area of Type III outgrowth zones was twice that
      of the Type II, with a neuronal density 2.5 times greater, composed of a near
      equal proportion of small to medium sized (10-18 MUm) neurons. The neuronal
      density and extent of migration of Type IV zones was similar to that of Type II
      zones; however the neurons of this fragment type were primarily medium and large
      sized neurons. In a second experiment the brachial region of E10 neural tube was
      sectioned into dorsal and ventral halves and microfragments from each half were
      cultured separately. Dorsal fragments produced primarily Type I and Type II
      outgrowth zones, and never a Type IV. In contrast, ventral fragments produced
      primarily Type III and Type IV zones with a small proportion of Type II zones.
      The results indicate that neuronal precursor cells in vitro maintain an adherence
      to patterns of neurogenesis programmed in vivo during early stages of neural tube
      development. The present culture system thus provides a means for the study of
      the expression in vitro of specific patterns of neuronal development and of the
      possible environmental influences (epigenetic factors) upon these patterns. 

PMID- 24874496
TI  - Changes in ganglioside profile in chick embryo retina: Studies on tissue and cell
      cultures.
AB  - The developmental profile of gangliosides in the neural retina of the chick
      embryo is characterized by a progressive decrease in the concentration of GD3
      complex from a high level on day 6; by a continuous increase in GD1a
      concentration; and by less striking increases in GD1b and GT1b concentrations
      during the growth phase; GM1 increases in the post-mitotic retina. Gangliosides
      were analyzed by thin layer chromatography and by densitometry of the TLC plates.
      (Ganglioside nomenclature is according to Svennerholm.(37)) We have examined
      comparatively ganglioside changes in organ cultures of retina tissue from 6 day
      embryos (R(36)), in cell aggregates and in primary monolayer cultures of R(26)
      cells, all maintained for 6 days in vitro. In all cases, the pattern of
      ganglioside changes was qualitatively similar to that in the retina in vivo.
      These results suggest that, unlike some other aspects of retina differentiation,
      the progression of ganglioside changes in the 6-12 day embryonic retina is not
      critically dependent on histotypic cell organization or on specific contact
      dependent cell interactions; these changes appear to be largely preprogrammed in
      the cells at some earlier phase of development. 

PMID- 24874495
TI  - Effects of prenatal alcohol exposure on neural cells in mice.
AB  - Pregnant DBA/1J mice were treated orally with 1.0 or 2.0 g/kg ethanol from days
      11-17 of gestation to determine whether ethanol can perturb normal brain
      development. On gestational day 18 the fetuses were removed and fetal growth
      parameters were determined. The cerebrums from one group of fetuses were
      subsequently analyzed for cell number and protein content. The remaining
      cerebrums were assayed for their ability to grow in an in vitro cell culture
      system. Prenatal ethanol exposure decreased fetal body and brain weights and
      crown-rump length. The brain was particularly affected as indicated by a
      decreased brain: body wt ratio. The percentage of affected and marginally
      affected fetuses increased in a dose-dependent manner. While the number of
      cells/brain was unaffected, the number of cells/g cerebrum and the number of
      cells/mg cerebral protein was increased. Prenatal ethanol exposure decreased the
      ability of cerebral cells to grow in culture as demonstrated by the reduced
      plating efficiency and reduced colony size. The data from the present study
      suggest that ethanol induces a two-fold effect on mouse brain development. First,
      since the total number of cells/brain was not appreciably affected by prenatal
      ethanol treatment, it is possible that the reduction in brain size is due to a
      decreased amount of neuropil. This putative effect on the neuropil was manifested
      in vitro by decreased colony area. Second, the decreased plating efficiency of
      cells from brains of affected fetuses suggests that these cells are not
      functionally normal. These effects may be important in the pathogenesis of
      central nervous system anomalies associated with the Fetal Alcohol Syndrome. 

PMID- 24874497
TI  - Perinatal development of adrenergic, cholinergic and non-adrenergic, non
      cholinergic nerves and sif cells in the rabbit urinary bladder.
AB  - The development of adrenergic (indicated by catecholamine fluorescence),
      acetylcholine-sterase-positive (possibly cholinergic), non-adrenergic, non
      cholinergic (indicated by quinacrine fluorescence) nerves and small intensely
      fluorescent (SIF) cells in the rabbit urinary bladder was examined in foetal
      (from 23 days of gestation), newborn and adult animals. Acetylcholinesterase
      positive nerve fibres and ganglion cells and quinacrine-positive ganglion cells
      were both present on day 23 of gestation, while quinacrine-positive varicose
      nerve fibres were first seen on day 24. At foetal age 26 days, 25-38 ganglia
      containing quinacrine-positive cells were seen in whole-mount preparations of
      detrusor muscle of the bladder. Each ganglion contained 30-40 quinacrine-positive
      cells (diameter 20-40 MUm). In contrast, only 5-12 ganglia contained
      acetylcholinesterase-positive nerve cell bodies at the same foetal age with only
      3-20 cells in each ganglion; these figures remained at about the same level from
      foetal age 23 days to maturity. No catecholamine-containing nerve cell bodies
      were seen at any foetal age or in the adult. Adrenergic nerve fibres were not
      detected until day 28 of gestation, although small intensely fluorescent cells
      were first observed on day 26 of gestation. In the adult bladder there was a
      reduction of approximately 25-35% in the number of quinacrine-positive nerve cell
      bodies within the ganglia when compared with the ganglia in 1-day-old bladders
      and an increase in nerve fibre density of about 50% when compared with bladders
      of earlier ages. A reduction of approximately 90% in small intensely fluorescent
      cells and a 2-fold increase of adrenergic nerves was also characteristic of the
      adult bladder, although no changes were observed in the density of the
      acetylcholinesterase-positive cell bodies and nerve fibres. It is concluded that
      catecholamine-containing, acetylcholinesterase-positive and non-adrenergic, non
      cholinergic nerves follow very different developmental patterns in the bladder. 

PMID- 24874498
TI  - Double-barreled colon conduit and colostomy for simultaneous urinary and fecal
      diversions: long-term follow-up.
AB  - BACKGROUND: Best strategies for simultaneous urinary and stool diversion remain
      indeterminate. Here we present what is to our knowledge the longest outcome data
      on double-barreled colon conduit and colostomy (DBCCC) in a cohort of patients
      needing simultaneous urinary and fecal diversion. METHODS: We identified 9
      patients who underwent DBCCC between March 2002 and March 2013. Nine patients who
      underwent separate urinary and fecal diversion (colostomy plus percutaneous
      nephrostomy or ureterocutaneostomy) served as the control group. We compared
      demographics, comorbidities, follow-up morbidities, and European Organization for
      Research and Treatment of Cancer Quality of Life Questionnaire-Core 30-item
      questionnaire in the two groups. RESULTS: The preservation of renal function was
      better in the DBCCC group. There were significant improvements in global state of
      health, fatigue, insomnia, appetite, bowel habit, and social function in the
      DBCCC group. In comparison with the separate urinary and fecal diversion group,
      the patients in the DBCCC group had statically significant improvement in global
      health status, functional scales, and symptom scales. CONCLUSIONS: Compared with
      the separate urinary and fecal diversion technique, DBCCC provides preservation
      of renal function, easy stoma bag care, better quality of life, and improved body
      image for patients who need simultaneous urinary and fecal diversion.

PMID- 24874499
TI  - Full-thickness closure in breast-conserving surgery: the impact on radiotherapy
      target definition for boost and partial breast irradiation. A multimodality image
      evaluation.
AB  - BACKGROUND: During breast-conserving surgery (BCS), surgeons increasingly perform
      full-thickness closure (FTC) to prevent seroma formation. This could potentially
      impair precision of target definition for boost and accelerated partial breast
      irradiation (APBI). The purpose of this study was to investigate the precision of
      target volume definition following BCS with FTC among radiation oncologists,
      using various imaging modalities. METHODS: Twenty clinical T1-2N0 patients,
      scheduled for BCS involving clip placement and FTC, were included in the study.
      Seven experienced breast radiation oncologists contoured the tumor bed on
      computed tomography (CT), magnetic resonance imaging (MRI) and fused CT-MRI
      datasets. A total of 361 observer pairs per image modality were analyzed. A
      pairwise conformity among the generated contours of the observers and the
      distance between their centers of mass (dCOM) were calculated. RESULTS: On CT,
      median conformity was 44 % [interquartile range (IQR) 28-58 %] and median dCOM
      was 6 mm (IQR 3-9 mm). None of the outcome measures improved when MRI or fused CT
      MRI were used. In two patients, superficial closure was performed instead of FTC.
      In these 14 image sets and 42 observer pairs, median conformity increased to 70
      %. CONCLUSIONS: Localization of the radiotherapy target after FTC is imprecise,
      on both CT and MRI. This could potentially lead to a geographical miss in
      patients at increased risk of local recurrence receiving a radiation boost, or
      for those receiving APBI. These findings highlight the importance for breast
      surgeons to clearly demarcate the tumor bed when performing FTC.

PMID- 24874500
TI  - Multidetector computed tomography of superior mesenteric artery: anatomy and
      pathologies.
AB  - The recent introduction of multidetector computed tomography scanners has
      significantly improved computed tomography angiographic (CTA) applications,
      especially for the evaluation of medium- and small-arterial structures. CTA of
      the superior mesenteric artery has been reported previously. However, there have
      been few systematic and detailed reviews of the superior mesenteric artery
      pathologies that use CTA. The purpose of this pictorial essay is mainly to review
      the various superior mesenteric artery pathologies at CTA with our own
      experiences.

PMID- 24874502
TI  - Growing the gerontological workforce through real-world research and practice:
      final thoughts.

PMID- 24874501
TI  - Mediators of neutrophil function in children with protracted bacterial
      bronchitis.
AB  - BACKGROUND: Protracted bacterial bronchitis (PBB) is a common and treatable cause
      of chronic wet cough in children in which the mechanisms are not understood. This
      study investigates the IL-1 pathway and a neutrophil gene expression signature in
      PBB. METHODS: BAL was collected from children in an experimental cohort (n = 21,
      PBB; n = 33, control subjects), and a second validation cohort (n = 36, PBB; n =
      11, control subjects). IL-1beta, IL-1 receptor antagonist (IL-1RA), and alpha
      defensins 1-3 were assayed by enzyme-linked immunosorbent assay, western blot,
      and quantitative real-time polymerase chain reaction, together with selected IL-1
      pathway members and neutrophil-related molecules. RESULTS: In the experimental
      cohort, children with symptomatic PBB had significantly higher levels of IL-1beta
      and alpha-defensin gene and protein expression. Expression of the neutrophil
      chemokine receptor C-X-C motif receptor 2 was also higher in PBB. IL-1RA protein
      was higher, however, the IL-1RA:IL-1beta ratio was lower in children with PBB
      than control subjects. In the validation cohort, protein and gene expression of
      IL-1beta and alpha-defensins 1-3 were confirmed higher, as was gene expression of
      IL-1 pathway members and C-X-C motif receptor 2. IL-1beta and alpha-defensin 1-3
      levels lowered when PBB was treated and resolved. In children with recurrent PBB,
      gene expression of the IL-1beta signaling molecules pellino-1 and IL-1 receptor
      associated kinase 2 was significantly higher. IL-1beta protein levels correlated
      with BAL neutrophilia and the duration and severity of cough symptoms. IL-1beta
      and alpha-defensin 1-3 levels were highly correlated. CONCLUSIONS: PBB is
      characterized by increased IL-1beta pathway activation. IL-1beta and related
      mediators were associated with BAL neutrophils, cough symptoms, and disease
      recurrence, providing insight into PBB pathogenesis.

PMID- 24874503
TI  - The impact of color combinations on the legibility of text presented on LCDs.
AB  - The paper investigates the impact of text and background color combinations on
      the legibility of text presented on LCDs. The legibility of 56 elementary color
      combinations was tested by 308 participants. The first task required the
      participants to identify 21 uppercase alphabetic characters selected and
      presented in conformance with a Snellen chart in various color combinations. For
      each color combination, the number of correctly identified characters was
      recorded as a visual performance measure. In the second task, participants
      subjectively rated the legibility of color combinations on a ten-point Likert
      scale. The results show that neither the Le Courier legibility table nor the CRT
      legibility table is appropriate for LCDs. A new legibility table is proposed for
      LCDs where the highest ranked are contrastive color combinations with positive
      polarity whereas for CRT displays, the highest ranked are contrastive color
      combinations with negative polarity. The findings of this study can be used to
      determine the best possible color combinations when developing content displayed
      on LCDs. 

PMID- 24874505
TI  - Seagrass meadows in a globally changing environment.
AB  - Seagrass meadows are valuable ecosystem service providers that are now being lost
      globally at an unprecedented rate, with water quality and other localised
      stressors putting their future viability in doubt. It is therefore critical that
      we learn more about the interactions between seagrass meadows and future
      environmental change in the anthropocene. This needs to be with particular
      reference to the consequences of poor water quality on ecosystem resilience and
      the effects of change on trophic interactions within the food web. Understanding
      and predicting the response of seagrass meadows to future environmental change
      requires an understanding of the natural long-term drivers of change and how
      these are currently influenced by anthropogenic stress. Conservation management
      of coastal and marine ecosystems now and in the future requires increased
      knowledge of how seagrass meadows respond to environmental change, and how they
      can be managed to be resilient to these changes. Finding solutions to such issues
      also requires recognising people as part of the social-ecological system. This
      special issue aims to further enhance this knowledge by bringing together global
      expertise across this field. The special issues considers issues such as
      ecosystem service delivery of seagrass meadows, the drivers of long-term seagrass
      change and the socio-economic consequences of environmental change to seagrass. 

PMID- 24874504
TI  - Seroprevalence and modifiable risk factors for Toxocara spp. in Brazilian
      schoolchildren.
AB  - BACKGROUND: Toxocariasis is a worldwide helminthic zoonosis caused by infection
      with the larvae of the ascarid worms that comprise the Toxocara spp. Children are
      particularly prone to infection because they are exposed to the eggs in sandboxes
      and playgrounds contaminated with dog and cat feces. Certain behaviors, such as a
      geophagy habit, poor personal hygiene, a lack of parental supervision, close
      contact with young dogs, and ingestion of raw meat, as well as gender, age, and
      socioeconomic status, affect the prevalence of the disease. However, previous
      studies of the risk factors for toxocariasis have generally produced inconsistent
      results. An epidemiological cross-sectional study was conducted to evaluate the
      seroprevalence of IgG anti-Toxocara spp. antibodies and associated factors in
      schoolchildren from a region in the southeast of Brazil. METHODOLOGY/PRINCIPAL
      FINDINGS: A total of 252 schoolchildren aged 1 to 12 years (120 males and 132
      females) were assessed. An enzyme-linked immunosorbent assay based on Toxocara
      canis larval excretory-secretory antigens was used to determine outcomes. A
      questionnaire was used to collect information on children, family, and home
      characteristics. Clinical and laboratory data completed the dataset investigated
      in this study. Seroprevalence was 15.5% (95%CI 11.5-19.8). Geophagy (aPR 2.38
      [95%CI 1.36-4.18], p-value 0.029) and the habit of hand washing before meals (aPR
      0.04 [95%CI 0.01-0.11], p-value <= 0.001) were factors associated with increased
      and decreased seroprevalence, respectively. The income factor and its related
      variables lost statistical significance after adjustment with a multiple Poisson
      regression model. CONCLUSIONS/SIGNIFICANCE: The current study confirms that
      toxocariasis is a public health problem in the evaluated area; modifiable factors
      such as soil contact and personal hygiene appear to have a greater influence on
      the acquisition of infection than sociodemographic attributes, thus representing
      direct targets for disease prevention and control.

PMID- 24874506
TI  - Respiration, growth and grazing rates of three ciliate species in hypoxic
      conditions.
AB  - Marine hypoxic episodes are affecting both marine and freshwater bodies all over
      the world. Yet, limited data exists with regard to the effects of decreasing
      oxygen on protist metabolism. Three ciliate species were therefore isolated from
      Hong Kong coastal waters. Controlled hypoxic conditions were simulated in the lab
      environment, during which time growth, respiration and grazing rates were
      measured. Euplotes sp. and a Oxytrichidae-like ciliate showed decreased growth
      and respiration below 2.5 mg O2 L(-1), however Uronema marinum kept steady growth
      and respiration until below 1.5 mg O2 L(-1). Euplotes sp. and the Oxytrichidae
      like ciliate had the highest ingestion rate, which dropped significantly below
      3.0 mg O2 L(-1). U.marinum grazing rates were affected at and below 1.5 mg O2 L(
      1), correlating with their drop in growth and respiration at this lower
      concentration. This study illustrates the slowing metabolism of key grazing
      protists, as well as species-specific tolerance in response to hypoxia.

PMID- 24874507
TI  - Development of Basal-Like HaCaT Keratinocytes Containing the Genome of Human
      Papillomavirus (HPV) Type 11 for Screening of Anti-HPV Effects.
AB  - Condylomata acuminata (CA), induced by low-risk human papillomaviruses (HPVs), is
      one of the most common sexually transmitted diseases. The increasing incidence
      and the high recurrence rate of CA have significantly contributed to public
      health problems around the world. Because HPVs cannot be cultured in vitro for a
      long time, there has been little progress in the development of HPV-specific
      antiviral agents. In this study, we established an HPV11.HaCaT system by
      introducing the recircularized genome of HPV-11 into HaCaT keratinocytes with
      transfection techniques and cultured them in a special medium. The existence and
      replication of HPV-11 DNA were positively detected in established HPV11.HaCaT
      cells. The HPV-11 DNA in HPV11.HaCaT cells has been stably replicated in definite
      passages of cells. We preliminarily studied the anti-HPV-11 effects of
      recombinant human interferon alpha1b (rhIFN-alpha) and 13-hexyl-palmatine
      hydrochloride (HP-13) in HPV11.HaCaT cells. The results suggest that HP-13
      significantly inhibited the proliferation of HPV11.HaCaT cells in a dose
      dependent manner, whereas rhIFN-alpha did not. HP-13 and rhIFN-alpha inhibited
      the replication of HPV-11 DNA and the expression of E1(?)E4 mRNA in HPV11.HaCaT
      cells. In conclusion, the established HPV11.HaCaT cells can provide us with a
      convenient and relatively stable tool for screening anti-HPV-11 agents. 

PMID- 24874508
TI  - "I can see clearly now": the effect of cue imageability on mental time travel.
AB  - Mental time travel (MTT) is the ability to mentally project oneself backward or
      forward in time, in order to remember an event from one's personal past or to
      imagine a possible event in one's personal future. Recent work has suggested
      that, although past and future MTT may rely on shared neurocognitive substrates,
      the two temporal directions may interact differently with components of this
      underlying system. Here, we asked 151 participants to recall or imagine past and
      future autobiographical events in response to high- and low-imageable cue words.
      The results showed that high- and low-imageable cued events differed markedly on
      almost all measures, suggesting that imagery acts as a facilitator when
      constructing both past and possible future events. In line with previous work,
      future events less often referred to specific events, contained fewer details,
      and were more positive and idyllic than past events. However, these main effects
      were qualified by a number of interactions. In particular, we found an increased
      effect of cue imageability for past as compared to future events, suggesting that
      the generation of past events is more sensitive to the ability of the cues to
      invoke the sensory components of the encoding context, whereas the construction
      of future events is more driven by context-independent schemata.

PMID- 24874509
TI  - The effects of environmental support and secondary tasks on visuospatial working
      memory.
AB  - In the present experiments, we examined the effects of environmental support on
      participants' ability to rehearse locations and the role of such support in the
      effects of secondary tasks on memory span. In Experiment 1, the duration of
      interitem intervals and the presence of environmental support for visuospatial
      rehearsal (i.e., the array of possible memory locations) during the interitem
      intervals were both manipulated across four tasks. When support was provided,
      memory spans increased as the interitem interval durations increased, consistent
      with the hypothesis that environmental support facilitates rehearsal. In
      contrast, when environmental support was not provided, spans decreased as the
      duration of the interitem intervals increased, consistent with the hypothesis
      that visuospatial memory representations decay when rehearsal is impeded. In
      Experiment 2, the ratio of interitem interval duration to intertrial interval
      duration was kept the same on all four tasks, in order to hold temporal
      distinctiveness constant, yet forgetting was still observed in the absence of
      environmental support, consistent with the decay hypothesis. In Experiment 3, the
      effects of impeding rehearsal were compared to the effects of verbal and
      visuospatial secondary processing tasks. Forgetting of locations was greater when
      presentation of to-be-remembered locations alternated with the performance of a
      secondary task than when rehearsal was impeded by the absence of environmental
      support. The greatest forgetting occurred when a secondary task required the
      processing visuospatial information, suggesting that in addition to decay, both
      domain-specific and domain-general effects contribute to forgetting on
      visuospatial working memory tasks.

PMID- 24874510
TI  - Examining competing hypotheses for the effects of diagrams on recall for text.
AB  - Supplementing text-based learning materials with diagrams typically increases
      students' free recall and cued recall of the presented information. In the
      present experiments, we examined competing hypotheses for why this occurs. More
      specifically, although diagrams are visual, they also serve to repeat information
      from the text they accompany. Both visual presentation and repetition are known
      to aid students' recall of information. To examine to what extent diagrams aid
      recall because they are visual or repetitive (or both), we had college students
      in two experiments (n = 320) read a science text about how lightning storms
      develop before completing free-recall and cued-recall tests over the presented
      information. Between groups, we manipulated the format and repetition of target
      pieces of information in the study materials using a 2 (visual presentation of
      target information: diagrams present vs. diagrams absent) * 2 (repetition of
      target information: present vs. absent) between-participants factorial design.
      Repetition increased both the free recall and cued recall of target information,
      and this occurred regardless of whether that repetition was in the form of text
      or a diagram. In contrast, the visual presentation of information never aided
      free recall. Furthermore, visual presentation alone did not significantly aid
      cued recall when participants studied the materials once before the test
      (Experiment 1) but did when they studied the materials twice (Experiment 2).
      Taken together, the results of the present experiments demonstrate the important
      role of repetition (i.e., that diagrams repeat information from the text) over
      the visual nature of diagrams in producing the benefits of diagrams for recall. 

PMID- 24874516
TI  - Spatiotemporally varying visual hallucinations: II. Spectral classification and
      comparison with theory.
AB  - In order to better understand the nature of visual hallucinations, and to test
      predictions of spatiotemporally oscillating hallucinations from a recent
      corticothalamic model of visual dynamics, clinical descriptions of hallucinations
      are used to establish boundaries on the spatiotemporal frequencies observed in
      various disorders. Detailed comparisons with hallucinations during migraine aura
      demonstrate that key features are consistent with corticothalamic origin and
      specific abnormalities, but underline the need for more detailed quantitative
      data to be obtained on temporally oscillating hallucinations more generally. 

PMID- 24874517
TI  - Spatiotemporally varying visual hallucinations: I. Corticothalamic theory.
AB  - The thalamus is introduced to a recent model of the visual cortex to examine its
      effect on pattern formation in general and the generation of temporally
      oscillating patterns in particular. By successively adding more physiological
      details to a basic corticothalamic model, it is determined which features are
      responsible for which effects. In particular, with the addition of a thalamic
      population, several changes occur in the spatiotemporal power spectrum: power
      increases at resonances of the corticothalamic loop, while the loop acts as a
      spatiotemporal low-pass filter, and synaptic and dendritic dynamics temporally
      low-pass filter the activity more generally. Investigation of the effect of
      altering parameters and gains reveals new parameter regimes where activity that
      corresponds to hallucinations is induced by both spatially homogeneous and
      inhomogeneous temporally oscillating modes. This suggests that the thalamus and
      corticothalamic loops are essential components of a model of oscillating visual
      hallucinations. 

PMID- 24874515
TI  - A new class of multimerization selective inhibitors of HIV-1 integrase.
AB  - The quinoline-based allosteric HIV-1 integrase (IN) inhibitors (ALLINIs) are
      promising candidates for clinically useful antiviral agents. Studies using these
      compounds have highlighted the role of IN in both early and late stages of virus
      replication. However, dissecting the exact mechanism of action of the quinoline
      based ALLINIs has been complicated by the multifunctional nature of these
      inhibitors because they both inhibit IN binding with its cofactor LEDGF/p75 and
      promote aberrant IN multimerization with similar potencies in vitro. Here we
      report design of small molecules that allowed us to probe the role of HIV-1 IN
      multimerization independently from IN-LEDGF/p75 interactions in infected cells.
      We altered the rigid quinoline moiety in ALLINIs and designed pyridine-based
      molecules with a rotatable single bond to allow these compounds to bridge between
      interacting IN subunits optimally and promote oligomerization. The most potent
      pyridine-based inhibitor, KF116, potently (EC50 of 0.024 uM) blocked HIV-1
      replication by inducing aberrant IN multimerization in virus particles, whereas
      it was not effective when added to target cells. Furthermore, KF116 inhibited the
      HIV-1 IN variant with the A128T substitution, which confers resistance to the
      majority of quinoline-based ALLINIs. A genome-wide HIV-1 integration site
      analysis demonstrated that addition of KF116 to target or producer cells did not
      affect LEDGF/p75-dependent HIV-1 integration in host chromosomes, indicating that
      this compound is not detectably inhibiting IN-LEDGF/p75 binding. These findings
      delineate the significance of correctly ordered IN structure for HIV-1 particle
      morphogenesis and demonstrate feasibility of exploiting IN multimerization as a
      therapeutic target. Furthermore, pyridine-based compounds present a novel class
      of multimerization selective IN inhibitors as investigational probes for HIV-1
      molecular biology. 

PMID- 24874518
TI  - Non-employment histories of middle-aged men and women who died from alcohol
      related causes: a longitudinal retrospective study.
AB  - BACKGROUND: Long-term patterning of non-employment among problem drinkers is
      poorly understood. We determined the level and timing of non-employment, and the
      relative contribution of various types of non-employment among middle-aged
      persons who died of alcohol-related causes. METHODS: We conducted a longitudinal
      retrospective register-based study of Finnish men and women aged 45-64 years who
      died of alcohol-related causes (n = 15,552) or other causes (n = 39,166) in the
      period 2000-07, or who survived (n = 204,422) until the end of 2007. We traced
      back the number of days in employment and non-employment for up to 17 years
      before death or before the end of the study period for the survivors. RESULTS:
      The majority (>=56%) of persons who died of alcohol-related causes were in
      employment up to ten years before death. Over the 17-year period before death,
      those who died of alcohol-related causes were in employment on average two years
      less (mean 6.3 years, 95%CI 6.2-6.4) than those dying of other causes (8.2, 8.1
      8.3), and five years less than survivors (11.6, 11.5-11.7), when sex and age were
      adjusted for. The relative role of various types of non-employment differed
      markedly across the two mortality groups. Among those who died of alcohol-related
      causes, unemployment accounted for 54% of the total burden of non-employment, in
      comparison with 29% among those who died of other causes. In contrast, disability
      pension accounted for 41% of the total burden of non-employment among those who
      died of alcohol-related causes, but 65% among those who died of other causes.
      CONCLUSIONS: The results indicate the feasibility of preventing movement out of
      employment among middle-aged men and women with severe alcohol-related harm,
      provided that they are identified early on during their working careers and
      offered effective interventions.

PMID- 24874519
TI  - Syntheses and structural investigation of some alkali metal ion-mediated LV(V)O2(
      ) (L(2-) = tridentate ONO ligands) species: DNA binding, photo-induced DNA
      cleavage and cytotoxic activities.
AB  - Eight alkali metal ion-mediated dioxidovanadium(v), [{V(V)O2L(1-6)}A(H2O)n]?,
      complexes for A = Li(+), Na(+), K(+) and Cs(+), containing tridentate
      aroylhydrazonate ligands coordinating via ONO donor atoms, are described. All the
      synthesised ligands and the metal complexes were successfully characterised by
      elemental analysis, IR, UV-Vis and NMR spectroscopy. X-ray crystallographic
      investigation of 3, 5-7 shows the presence of distorted NO4 coordination
      geometries for LVO2(-) in each case, and varying MU-oxido and/or MU-aqua bridging
      with interesting variations correlated with the size of the alkali metal ions:
      with small Li(+), no bridging-O is found but four ion aggregates are found with
      Na(+), chains for K(+) and finally, layers for Cs(+). Two (5) or three
      dimensional (3, 6 and 7) architectures are consolidated by hydrogen bonding. The
      dioxidovanadium(v) complexes were found to exhibit DNA binding activity due to
      their interaction with CT-DNA by the groove binding mode, with binding constants
      ranging from 10(3) to 10(4) M(-1). Complexes 1-8 were also tested for DNA
      nuclease activity against pUC19 plasmid DNA which showed that 6 and 7 had the
      best DNA binding and photonuclease activity; these results support their good
      protein binding and cleavage activity with binding constants ranging from 10(4)
      to 10(5) M(-1). Finally, the in vitro antiproliferative activity of all complexes
      was assayed against the HeLa cell line. Some of the complexes (2, 5, 6 and 7)
      show considerable activity compared to commonly used chemotherapeutic drugs. The
      variation in cytotoxicity of the complexes is influenced by the various
      functional groups attached to the aroylhydrazone derivative. 

PMID- 24874521
TI  - Different levels of implicit emotional recognition in posterior cortical atrophy
      (PCA).
AB  - Previous single-case reports in posterior cortical atrophy (PCA) have shown
      preserved nonconscious visual recognition despite the absence of explicit
      recognition. In this study, we investigated three levels of visual recognition in
      both a female patient with PCA and a control group during the presentation of
      neutral, positive, and negative affective stimuli. Our results confirmed the
      profile of impaired explicit recognition and intact psychophysiological responses
      in the patient. In addition, she was able to implicitly recognize the valence and
      intensity of arousal of these stimuli. We suggest that implicit emotional
      awareness may mediates explicit and psychophysiological recognition in PCA. 

PMID- 24874523
TI  - [Type 2 diabetes mellitus in adolescents in a pediatric diabetes unit].

PMID- 24874524
TI  - [Multiple cavernomatosis: a review and presentation of a familial case].

PMID- 24874522
TI  - Ochratoxin A and human health risk: a review of the evidence.
AB  - Ochratoxin A (OTA) is a mycotoxin produced by several fungal species including
      Aspergillus ochraceus, A. carbonarius, A. niger, and Penicillium verrucosum. OTA
      causes nephrotoxicity and renal tumors in a variety of animal species; however,
      human health effects are less well-characterized. Various studies have linked OTA
      exposure with the human diseases Balkan endemic nephropathy (BEN) and chronic
      interstitial nephropathy (CIN), as well as other renal diseases. This study
      reviews the epidemiological literature on OTA exposure and adverse health effects
      in different populations worldwide, and assesses the potential human health risks
      of OTA exposure. Epidemiological studies identified in a systematic review were
      used to calculate unadjusted odds ratios for OTA associated with various health
      endpoints. With one exception, there appears to be no statistically significant
      evidence for human health risks associated with OTA exposure. One Egyptian study
      showed a significantly higher risk of nephritic syndrome in those with very high
      urinary OTA levels compared with relatively unexposed individuals; however, other
      potential risk factors were not controlled for in the study. Larger cohort or
      case-control studies are needed in the future to better establish potential OTA
      related human health effects, and further duplicate-diet studies are needed to
      validate biomarkers of OTA exposure in humans.

PMID- 24874525
TI  - [Intestinal injury due to blunt abdominal trauma. Surgical indication based on
      diagnostic imaging].

PMID- 24874526
TI  - Living with Parkinson's disease: priorities for research suggested by patients.
AB  - PURPOSE: To describe a study in which patients with Parkinson's disease (PD) were
      engaged to list priorities for research to complement the professionals' research
      agenda. METHOD: The study was conducted by researchers and people with PD or
      relatives. Interviews and focus groups were held to develop a research agenda
      from patients' perspectives. A questionnaire was completed by patients to
      prioritize the research topics. Voiceover group meetings and meetings with the
      advisory group were organized to obtain feedback on the research process and to
      deliberate the preliminary findings. Finally, dialog meetings were organized with
      stakeholders to discuss the agenda and to achieve a shared research agenda.
      RESULTS: Patients prioritized 18 research themes. Top priorities included
      fundamental research, research on medication, coping, family & relations and good
      care. Patients asked for applied and multidisciplinary research. Professionals
      and charitable funding bodies acknowledged the importance of such research but
      did not feel capable of judging such proposals. Patients furthermore asked for
      more attention to be paid to living with the illness in the here-and-now to
      complement fundamental research. CONCLUSIONS: The patients' research agenda can
      be used to match research with patients' needs and to adapt the clinical support
      of professionals to patients' wishes.

PMID- 24874527
TI  - Is radiological shortening of the ramus a reliable guide to operative management
      of unilateral fractures of the mandibular condyle?
AB  - Several studies have published measurements of the height of the ramus on
      orthopantomographic (OPT) images of patients with unilateral fractures of the
      mandibular condyle as a possible quantitative measure for making decisions about
      treatment. However, we know of no studies that have described the accuracy and
      validity of such measurements. The aim of the present study was to assess the
      shortening of the ramus in patients with such fractures, and compare them with
      differences found in a control group. Seventy-four patients and 74 controls were
      studied. The height of the ramus on the fractured was less than that on the
      uninjured side, although this was not statistically significant (p=0.25). In the
      control group, 50 subjects (68%) had a difference in the ramal height of more
      than 2mm. Of 74 patients, 25 (34%) had a shorter, uninjured ramus on the opposite
      side. A Bland and Altman scatterplot showed 23 outliers (31%) among the patients,
      which exceeded the mean (SD 1.96) of the control group. The interobserver and
      intraobserver reliability both showed excellent agreement for all measurements
      made. Shortening of the ramus can be measured on OPT images. However, in a
      control group there was a large mean difference in height. Among the patients,
      25/74 (34%) also had an uninjured ramus on the opposite side that was shorter
      than that on the fractured side. Measurement of the difference in height on an
      OPT image cannot be relied on as an absolute indication for intervention. 

PMID- 24874528
TI  - Enhancing brain lesions after endovascular treatment of aneurysms.
AB  - Complications of endovascular therapy of aneurysms mainly include aneurysm
      rupture and thromboembolic events. The widespread use of MR imaging for follow-up
      of these patients revealed various nonvascular complications such as aseptic
      meningitis, hydrocephalus, and perianeurysmal brain edema. We present 7 patients
      from 5 different institutions that developed MR imaging-enhancing brain lesions
      after endovascular therapy of aneurysms, detected after a median time of 63 days.
      The number of lesions ranged from 4-46 (median of 10.5), sized 2-20 mm, and were
      mostly in the same vascular territory used for access. Three patients presented
      with symptoms attributable to these lesions. After a median follow-up of 21.5
      months, the number of lesions increased in 2, was stable in 1, decreased in 3,
      and disappeared in 1. The imaging and clinical characteristics suggested a
      foreign body reaction. We could find no correlation to a specific device, but a
      possible source may be the generic hydrophilic coating.

PMID- 24874529
TI  - Enhanced repair effect of toll-like receptor 4 activation on neurotmesis:
      assessment using MR neurography.
AB  - BACKGROUND AND PURPOSE: Alternative use of molecular approaches is promising for
      improving nerve regeneration in surgical repair of neurotmesis. The purpose of
      this study was to determine the role of MR imaging in assessment of the enhanced
      nerve regeneration with toll-like receptor 4 signaling activation in surgical
      repair of neurotmesis. MATERIALS AND METHODS: Forty-eight healthy rats in which
      the sciatic nerve was surgically transected followed by immediate surgical
      coaptation received intraperitoneal injection of toll-like receptor 4 agonist
      lipopolysaccharide (n = 24, study group) or phosphate buffered saline (n = 24,
      control group) until postoperative day 7. Sequential T2 measurements and
      gadofluorine M-enhanced MR imaging and sciatic functional index were obtained
      over an 8-week follow-up period, with histologic assessments performed at regular
      intervals. T2 relaxation times and gadofluorine enhancement of the distal nerve
      stumps were measured and compared between nerves treated with lipopolysaccharide
      and those treated with phosphate buffered saline. RESULTS: Nerves treated with
      lipopolysaccharide injection achieved better functional recovery and showed more
      prominent gadofluorine enhancement and prolonged T2 values during the
      degenerative phase compared with nerves treated with phosphate buffered saline.
      T2 values in nerves treated with lipopolysaccharide showed a more rapid return to
      baseline level than did gadofluorine enhancement. Histology exhibited more
      macrophage recruitment, faster myelin debris clearance, and more pronounced nerve
      regeneration in nerves treated with toll-like receptor 4 activation. CONCLUSIONS:
      The enhanced nerve repair with toll-like receptor 4 activation in surgical repair
      of neurotmesis can be monitored by using gadofluorine M-enhanced MR imaging and
      T2 relaxation time measurements. T2 relaxation time seems more sensitive than
      gadofluorine M-enhanced MR imaging for detecting such improved nerve
      regeneration.

PMID- 24874531
TI  - Comparative effectiveness research.
AB  - The goal of comparative effectiveness research is to improve health care while
      dealing with the seemingly ever-rising cost. An understanding of comparative
      effectiveness research as a core topic is important for neuroradiologists. It can
      be used in a variety of ways. Its goal is to look at alternative methods of
      interacting with a clinical condition, ideally, while improving delivery of care.
      While the Patient-Centered Outcome Research initiative is the most mature US
      based foray into comparative effectiveness research, it has been used more
      robustly in decision-making in other countries for quite some time. The National
      Institute for Health and Clinical Excellence of the United Kingdom is a
      noteworthy example of comparative effectiveness research in action.

PMID- 24874532
TI  - Interhypothalamic adhesion: a series of 13 cases.
AB  - Interhypothalamic adhesion is a newly described disease entity, characterized by
      an abnormal parenchymal band connecting the medial margins of the hypothalami
      across the third ventricle. Additional anomalies, including cleft palate, gray
      matter heterotopia, cerebellar hypoplasia, optic atrophy, hippocampal under
      rotation, and white matter lesions, may coexist. The purpose of this clinical
      report is to describe the imaging findings from a series of 13 patients with
      interhypothalamic adhesions discovered on brain MR imaging.

PMID- 24874530
TI  - Orbital lymphoproliferative disorders (OLPDs): value of MR imaging for
      differentiating orbital lymphoma from benign OPLDs.
AB  - BACKGROUND AND PURPOSE: Accurate discrimination of orbital lymphoma from benign
      orbital lymphoproliferative disorders is crucial for treatment planning. We
      evaluated MR imaging including DWI and contrast-enhanced MR imaging for
      differentiating orbital lymphoma from benign orbital lymphoproliferative
      disorders. MATERIALS AND METHODS: Forty-seven histopathologically proved orbital
      lymphoproliferative disorders (29 orbital lymphomas and 18 benign orbital
      lymphoproliferative disorders) were evaluated. Two board-certified radiologists
      reviewed visual features on T1-weighted, fat-suppressed T2-weighted, diffusion
      weighted, and contrast-enhanced MR images. For quantitative evaluation, ADC and
      contrast-enhancement ratio of all lesions were measured and optimal cutoff
      thresholds and areas under curves for differentiating orbital lymphoma from
      benign orbital lymphoproliferative disorders were determined using receiver
      operative characteristic analysis; corresponding sensitivities and specificities
      were calculated. RESULTS: Multivariate logistic regression analysis showed that
      ill-defined tumor margin (P = .003) had a significant association with orbital
      lymphoma whereas the "flow void sign" (P = .005) and radiologic evidence of
      sinusitis (P = .0002) were associated with benign orbital lymphoproliferative
      disorders. The mean ADC and contrast-enhancement ratio of orbital lymphomas were
      significantly lower than those of benign orbital lymphoproliferative disorders (P
      < .01). An ADC of less than 0.612 * 10(-3) mm(2)/s and a contrast-enhancement
      ratio of less than 1.88 yielded areas under curves of 0.980 and 0.770,
      sensitivity of 94.1% and 95.5%, and specificities of 93.3% and 80.0% for
      predicting orbital lymphoma, respectively. CONCLUSIONS: Some characteristic MR
      imaging features and quantitative DWI and contrast-enhanced MR imaging are useful
      in further improving the accuracy of MR imaging for differentiation of orbital
      lymphoma from benign orbital lymphoproliferative disorders.

PMID- 24874533
TI  - Transforaminal versus intra-articular facet corticosteroid injections for the
      treatment of cervical radiculopathy: a randomized, double-blind, controlled
      study.
AB  - BACKGROUND AND PURPOSE: Transforaminal corticosteroid injections can be performed
      in the management of cervical radiculopathy but carry the risk of catastrophic
      complications. This study compares the efficacy of transforaminal and facet
      corticosteroid injections at 4 weeks' follow-up. MATERIALS AND METHODS: We
      randomly assigned 56 subjects to receive CT-guided transforaminal (15 men, 13
      women; mean age, 52 years; range, 28-72 years) or facet (8 men, 20 women; mean,
      44 years; range, 26-60 years) injections. The primary outcome was pain severity
      rated on a Visual Analog Scale (0-100). Secondary outcomes were the Neck
      Disability Index and the Medication Quantitative Scale. RESULTS: In the intention
      to-treat and as-treated analyses, for a mean baseline score, facet injections
      demonstrated a significant pain score reduction of 45.3% (95% CI, 21.4-69.2) and
      37.0% (95% CI, 9.2-64.7), while transforaminal injections showed a nonsignificant
      pain score reduction of 9.8% (95% CI, +11.5-31.2) and 17.8% (95% CI, +6.6-42.2).
      While facet injections demonstrated an improvement in the Neck Disability Index
      score of 24.3% (95% CI, +2.9-51.5) and 20.7% (95% CI, +6.2-47.6) as opposed to
      transforaminal injections of 9.6% (95% CI, +15.2-34.4) and 12.8% (95% CI, +11.2
      36.7), the results were not statistically significant. Noninferiority of facet to
      transforaminal injections was demonstrated for baseline pain scores of <=60,
      while noninferiority analysis was inconclusive for baseline pain scores of >=80
      and for the Neck Disability Index. Neither intervention showed a significant
      medication-intake score reduction with time. CONCLUSIONS: Facet injections are
      effective for the treatment of cervical radiculopathy and represent a valid and
      safer alternative to transforaminal injections.

PMID- 24874534
TI  - Impaired white matter development in extremely low-birth-weight infants with
      previous brain hemorrhage.
AB  - BACKGROUND AND PURPOSE: Brain hemorrhage is common in premature infants. The
      purpose of the study is to evaluate white matter development in extremely low
      birth-weight infants with or without previous brain hemorrhage. MATERIALS AND
      METHODS: Thirty-three extremely low-birth-weight infants were prospectively
      enrolled and included in this institutional review board-approved study. Another
      10 healthy term infants were included as controls. The medical records of the
      extremely low-birth-weight infants were reviewed for sonography diagnosis of
      intraventricular hemorrhage. All infants had an MR imaging examination at term
      equivalent age for detection of previous hemorrhage, and their white matter was
      scored and compared among different groups. DTI measured fractional anisotropy
      values were also compared voxelwise by tract-based spatial statistics. RESULTS:
      Compared with controls, the white matter score was not significantly different in
      extremely low-birth-weight infants without blood deposition on MR imaging (P =
      .17), but was significantly worse in extremely low-birth-weight infants with
      blood deposition on MR imaging but no intraventricular hemorrhage diagnosis by
      sonography (P = .02), in extremely low-birth-weight infants with grade 1 or 2
      intraventricular hemorrhage on sonography (P = .003), and in extremely low-birth
      weight infants with grade 3 or 4 intraventricular hemorrhage on sonography (P =
      .0001). Extremely low-birth-weight infants without blood deposition on MR imaging
      did not show any white matter regions with significantly lower fractional
      anisotropy values than controls. Extremely low-birth-weight infants with blood
      deposition on MR imaging, but no intraventricular hemorrhage diagnosis, did show
      white matter regions with significantly lower fractional anisotropy values, and
      extremely low-birth-weight infants with intraventricular hemorrhage diagnosis had
      widespread white matter regions with lower fractional anisotropy values.
      CONCLUSIONS: Previous brain hemorrhage is associated with abnormal white matter
      in extremely low-birth-weight infants at term-equivalent age, and sonography is
      not sensitive to minor hemorrhages that are sufficient to cause white matter
      injury.

PMID- 24874535
TI  - Collateral score complements clot location in predicting the outcome of
      intravenous thrombolysis.
AB  - BACKGROUND AND PURPOSE: Collateral circulation is an important determinant of
      stroke outcome. We studied the impact of leptomeningeal collateral circulation
      with respect to the location of the thrombus in predicting the clinical outcome
      of patients treated with intravenous thrombolytic therapy (<3 hours) in a
      retrospective cohort. MATERIALS AND METHODS: Anterior circulation thrombus was
      detected with CT angiography in 105 patients. Baseline clinical and imaging
      information was collected, and the site of the occlusion was recorded.
      Collaterals were assessed by using a 5-grade collateral score and were entered
      into logistic regression analysis to predict favorable clinical outcome (3-month
      modified Rankin Scale score of 0-2). RESULTS: Two-thirds of patients with a
      proximal occlusion displayed poor collateral filling (collateral score 0-1),
      whereas in more distal clot locations, approximately one-third had poor
      collaterals. Only 36% of patients with a proximal occlusion and good collaterals
      experienced favorable clinical outcome. In multivariate analysis, both clot
      location and collateral score were highly significant (P = .003 and P = .001) and
      independent predictors of favorable clinical outcome. Good collateral status
      increased the odds of favorable clinical outcome about 9-fold (OR = 9.3; 95% CI,
      2.4-35.8). After dichotomization, a distal clot location had a larger odds ratio
      (OR = 13.3; 95% CI, 3.0-60.0) compared with the odds ratio of good collaterals
      (OR = 5.9; 95% CI, 1.8-19.0). CONCLUSIONS: A proximal occlusion in the anterior
      circulation is associated with poorer collateral status compared with a more
      distal occlusion. Both the clot location and collateral score are important and
      independent predictors of favorable clinical outcome of hyperacute stroke treated
      with intravenous thrombolysis. The location of the clot is a stronger determinant
      of the outcome than the collateral score.

PMID- 24874538
TI  - Lymphogranuloma venereum: the first case in Lebanon.

PMID- 24874537
TI  - When can HIV clinical trials detect treatment effects on drug resistance?
AB  - Methods of sampling patients for resistance testing, and statistical analyses of
      HIV drug resistance, have not been standardised in HIV clinical trials. We
      analysed methods of genotyping and rates of treatment-emergent drug resistance
      from 27 clinical trials identified from a MEDLINE search. Sample size
      calculations were conducted using NQUERY software, assuming 5% significance
      level, 80% power and 1:1 randomisation. The percentage of patients with treatment
      emergent IAS-USA mutations after 96 weeks ranged from 1.8% to 9.1% for first-line
      2NRTI/NNRTI treatments, 0.6% to 6.3% for first-line 2NRTI/PI/r treatments and
      0.0% to 2.0% in switch trials of boosted PIs. The prevalence of drug resistance
      was higher in trials with no screening for drug resistance at baseline, where the
      HIV RNA cut-off for genotyping was >50 copies/mL, where patients were tested for
      drug resistance after discontinuation of treatment, and where follow-up times
      were 96 weeks or longer. HIV clinical trials could be designed to detect
      differences in the risk of HIV drug resistance between treatments, as an analysis
      supporting HIV RNA suppression as the primary endpoint. However, this would
      require a standardised approach, with intent-to-treat analyses, testing of all
      samples with HIV RNA>50 copies/mL and genotyping after drug discontinuation.

PMID- 24874536
TI  - Phase white matter signal abnormalities in patients with clinically isolated
      syndrome and other neurologic disorders.
AB  - BACKGROUND AND PURPOSE: Identifying MRI biomarkers that can differentiate
      multiple sclerosis patients from other neurological disorders is a subject of
      intense research. Our aim was to investigate phase WM signal abnormalities for
      their presence, prevalence, location, and diagnostic value among patients with
      clinically isolated syndrome and other neurologic disorders and age-, sex-, and
      group-matched healthy controls. MATERIALS AND METHODS: Forty-eight patients with
      clinically isolated syndrome and 30 patients with other neurologic diseases and a
      healthy control group (n = 47) were included in the study. Subjects were scanned
      at 3T by using SWI-filtered phase and T2WI, with WM signal abnormalities >=3 mm
      being classified. RESULTS: Patients with clinically isolated syndrome had
      significantly more phase and T2 WM signal abnormalities than healthy controls (P
      < .001). Phase WM signal abnormalities were more prevalent among patients with
      clinically isolated syndrome compared with patients with other neurologic
      disorders (4:1 ratio), whereas T2 WM signal abnormalities were more ubiquitous
      with a 2:1 ratio. The presence of phase WM signal abnormalities was sensitive for
      clinically isolated syndrome (70.8%) and achieved a moderate-to-high specificity
      for differentiating patients with clinically isolated syndrome and healthy
      controls, patients with other neurologic disorders, and patients with other
      neurologic disorders of other autoimmune origin (specificity, 70%-76.7%).
      Combining the presence of >=2 phase lesions with the McDonald 2005 and 2010
      criteria for dissemination in space improved the specificity (90%), but not the
      accuracy, in differentiating patients with clinically isolated syndrome from
      those with other neurologic disorders. In subanalyses among patients with
      clinically isolated syndrome who converted to clinically definite multiple
      sclerosis versus those who did not within a 3-year follow-up period, converters
      had significantly more phase (P = .008) but not T2 or T1 WM signal abnormalities.
      CONCLUSIONS: Phase WM signal abnormalities are prevalent among patients with
      clinically isolated syndrome. The presence of (multiple) phase WM signal
      abnormalities tended to be more predictive of conversion to clinically definite
      multiple sclerosis and was specific in differentiating patients with clinically
      isolated syndrome and other neurologic disorders, compared with T2 WM signal
      abnormalities; however, the accuracy remains similar to that of the current
      McDonald criteria.

PMID- 24874539
TI  - Jak2 inhibitor--a jackpot for pharmaceutical industries: a comprehensive
      computational method in the discovery of new potent Jak2 inhibitors.
AB  - A potent Jak2 inhibitor could solve numerous diseases including hypertension and
      cardiovascular diseases, myeloproliferative neoplasms, polycythemia vera,
      essential thrombocythemia, primary myelofibrosis, psoriasis and rheumatoid
      arthritis. So, identifying potent Jak2 inhibitors is of great interest to
      researchers and pharmaceutical companies. Virtual screening and molecular docking
      are important tools for structure based drug discovery but selecting an
      appropriate method to calculate the electrostatic potential is critical. In this
      study, four semi empirical (AM1, RM1, PM3, and MNDO) and two empirical (DFT, HF)
      charges were investigated for their performance on the prediction of docking pose
      using Glide XP. The result shows that AM1 has the best charge model for our
      study. Further, we performed a 3D-quantitative structure-activity relationship
      (3D-QSAR) study of 76 decaene derivatives. Since 3D-QSAR methods are known to be
      highly sensitive to ligand conformation and alignment method, we did a
      comparative 3D-QSAR study of AM1 charge docked pose alignment based QSAR
      (structure based) and pharmacophore based QSAR. We found a better QSAR model in
      the structure based method. Hence, the results clearly demonstrate that selecting
      an appropriate method to calculate the electrostatic potential for docking
      studies and a good alignment of the ligand for 3D-QSAR is critical. Finally,
      extensive pharmacophore and e-pharmacophore based virtual screening followed by
      subsequent docking studies identified 27 lead molecules which could be potent
      Jak2 inhibitors. 

PMID- 24874540
TI  - Learn from the best.
AB  - What is more inspiring than a discussion with the leading scientists in your
      field? As a student or a young researcher, you have likely been influenced by
      mentors guiding you in your career and leading you to your current position. Any
      discussion with or advice from an expert is certainly very helpful for young
      people. But how often do we have the opportunity to meet experts? Do we make the
      most out of these situations? Meetings organized for young scientists are a great
      opportunity not only for the attendees: they are an opportunity for experts to
      meet bright students and learn from them in return. In this article, we introduce
      several successful events organized by Regional Student Groups all around the
      world, bridging the gap between experts and young scientists. We highlight how
      rewarding it is for all participants: young researchers, experts, and organizers.
      We then discuss the various benefits and emphasize the importance of organizing
      and attending such meetings. As a young researcher, seeking mentorship and
      additional skills training is a crucial step in career development. Keep in mind
      that one day, you may be an inspiring mentor, too. 

PMID- 24874541
TI  - GABAA receptor biogenesis is impaired by the gamma2 subunit febrile seizure
      associated mutation, GABRG2(R177G).
AB  - A missense mutation in the GABAA receptor gamma2L subunit, R177G, was reported in
      a family with complex febrile seizures (FS). To gain insight into the mechanistic
      basis for these genetic seizures, we explored how the R177G mutation altered the
      properties of recombinant alpha1beta2gamma2L GABAA receptors expressed in HEK293T
      cells. Using a combination of electrophysiology, flow cytometry, and
      immunoblotting, we found that the R177G mutation decreased GABA-evoked whole-cell
      current amplitudes by decreasing cell surface expression of alpha1beta2gamma2L
      receptors. This loss of receptor surface expression resulted from endoplasmic
      reticulum (ER) retention of mutant gamma2L(R177G) subunits, which unlike wild
      type gamma2L subunits, were degraded by ER-associated degradation (ERAD).
      Interestingly, when compared to the condition of homozygous gamma2L(R177G)
      subunit expression, disproportionately low levels of gamma2L(R177G) subunits
      reached the cell surface with heterozygous expression, indicating that wild-type
      gamma2L subunits possessed a competitive advantage over mutant gamma2L(R177G)
      subunits for receptor assembly and/or forward trafficking. Inhibiting protein
      synthesis with cycloheximide demonstrated that the R177G mutation primarily
      decreased the stability of an intracellular pool of unassembled gamma2L subunits,
      suggesting that the mutant gamma2L(R177G) subunits competed poorly with wild-type
      gamma2L subunits due to impaired subunit folding and/or oligomerization.
      Molecular modeling confirmed that the R177G mutation could disrupt intrasubunit
      salt bridges, thereby destabilizing secondary and tertiary structure of
      gamma2L(R177G) subunits. These findings support an emerging body of literature
      implicating defects in GABAA receptor biogenesis in the pathogenesis of genetic
      epilepsies (GEs) and FS. 

PMID- 24874542
TI  - Interleukin-1beta mediated amyloid plaque clearance is independent of CCR2
      signaling in the APP/PS1 mouse model of Alzheimer's disease.
AB  - Neuroinflammation is a key component of Alzheimer's disease (AD) pathogenesis.
      Particularly, the proinflammatory cytokine interleukin-1 beta (IL-1beta) is
      upregulated in human AD and believed to promote amyloid plaque deposition.
      However, studies from our laboratory have shown that chronic IL-1beta
      overexpression in the APPswe/PSEN1dE9 (APP/PS1) mouse model of AD ameliorates
      amyloid pathology, increases plaque-associated microglia, and induces recruitment
      of peripheral immune cells to the brain parenchyma. To investigate the
      contribution of CCR2 signaling in IL-1beta-mediated amyloid plaque clearance,
      seven month-old APP/PS1/CCR2(-/-) mice were intrahippocampally transduced with a
      recombinant adeno-associated virus serotype 2 containing the cleaved form of
      human IL-1beta (rAAV2-IL-1beta). Four weeks after rAAV2-IL-1beta transduction, we
      found significant reductions in 6E10 and Congo red staining of amyloid plaques
      that was confirmed by decreased levels of insoluble Abeta1-42 and Abeta1-40 in
      the inflamed hippocampus. Bone marrow chimeric studies confirmed the presence of
      infiltrating immune cells following IL-1beta overexpression and revealed that
      dramatic reduction of CCR2(+) peripheral mononuclear cell recruitment to the
      inflamed hippocampus did not prevent the ability of IL-1beta to induce amyloid
      plaque clearance. These results suggest that infiltrating CCR2(+) monocytes do
      not contribute to IL-1beta-mediated amyloid plaque clearance. 

PMID- 24874544
TI  - Does gender influence susceptibility and consequences of acquired epilepsies?
AB  - Gender differences in the incidence and clinical course of acquired and
      "cryptogenic" epilepsy are reviewed based on a literature search. We emphasized
      incidence and population-based studies because they are best suited to assess the
      effect of gender on susceptibility and clinical evolution of these epilepsies and
      may control for potential confounding factors. However, such studies were only
      available for a few acquired etiologies. These included tumor, prenatal and
      perinatal brain insults, cerebrovascular disease, infection, trauma,
      neurodegenerative disease, and autoimmune disorders. None of these acquired
      causes has been consistently shown to affect women or men to a greater or lesser
      degree, although some of the literature is contradictory or inadequate. There is
      almost no literature that addresses the effect of gender on the clinical course
      of epilepsy associated with these acquired causes. In addition, most studies of
      acquired causes do not take into account the incidence of the cause in the
      population with or without associated epilepsy. In children, "cryptogenic"
      epilepsy (non-syndromic and without causative MRI lesion) does not appear to have
      a gender preference and gender does not seem to affect the likelihood of
      remission. As further population-based studies of the etiology and clinical
      course of epilepsy are undertaken, it may be worthwhile to more specifically
      define the role of gender.

PMID- 24874543
TI  - Anti-neutrophil antibody enhances the neuroprotective effects of G-CSF by
      decreasing number of neutrophils in hypoxic ischemic neonatal rat model.
AB  - OBJECTIVES: Neonatal hypoxia ischemia (HI) is an injury that can lead to
      neurological impairments such as behavioral and learning disabilities.
      Granulocyte-colony stimulating factor (G-CSF) has been demonstrated to be
      neuroprotective in ischemic stroke however it has also been shown to induce
      neutrophilia, ultimately exacerbating neuronal injury. Our hypothesis is that
      coadministration of anti-neutrophil antibody (Ab) with G-CSF will decrease blood
      neutrophil counts thereby reducing infarct volume and improving neurological
      function post HI brain injury. METHODS: Rat pups were subjected to unilateral
      carotid artery ligation followed by 2.5h of hypoxia. Animals were randomly
      assigned to five groups: Sham (n=15), vehicle (HI, n=15), HI with G-CSF treatment
      (n=15), HI with G-CSF+Ab treatment (n=15), and HI with Ab treatment (n=15). Ab
      (325MUg/kg) was administered intraperitoneally while G-CSF (50MUg/kg) was
      administered subcutaneously 1h post HI followed by daily injections for 3
      consecutive days. Animals were euthanized at 96h post HI for blood neutrophil
      counts and brain infarct volume measurements as well as at 5weeks for
      neurological function testing and brain weight measurements. Lung and spleen
      weights at both time points were further analyzed. RESULTS: The G-CSF treatment
      group showed tendencies to reduce infarct volume and improve neurological
      function while significantly increasing neutrophil counts. On the other hand, the
      G-CSF+Ab group significantly reduced infarct volume, improved neurological
      function and decreased neutrophil counts. The Ab alone group showed reversal of
      the neuroprotective effects of the G-CSF+Ab group. No significant differences
      were found in peripheral organ weights between groups. CONCLUSION: Our data
      suggest that coadministration of G-CSF with Ab not only prevented brain atrophy
      but also significantly improved neurological function by decreasing blood
      neutrophil counts. Hence the neuroprotective effects of G-CSF may be further
      enhanced if neutrophilia is avoided.

PMID- 24874545
TI  - Long-term modifications of epileptogenesis and hippocampal rhythms after
      prolonged hyperthermic seizures in the mouse.
AB  - Complex febrile seizures are often reported in the history of patients with mesio
      temporal lobe epilepsy (MTLE) but their role in its physiopathology remains
      controversial. We postulated that prolonged hyperthermic seizures might, as a
      "single-hit", modify the hippocampal rhythms, facilitate epileptogenesis and
      influence subsequent epilepsy when a second-hit already exists or subsequently
      occurs. To test this hypothesis, we examined the effects of hyperthermic seizures
      (30min at 40-41 degrees C) at postnatal day 10 on hippocampal activity in
      C57BL/6J mice in comparison to their littermates in sham conditions (22 degrees
      C), with or without another insult. Using local field potential, we observed an
      asymmetry in the hippocampal susceptibility to seize in hyperthermic conditions.
      When these mice were adult, an asymmetrical increase of low frequency power was
      also recorded in the hippocampus when compared to sham animals. Using two
      different "two-hit" protocols, no increase in seizures or hippocampal discharge
      frequency or duration was observed, either in mice with a genetic CA3 dysplasia
      (Dcx knockout), or in mice injected with kainate into the dorsal hippocampus at
      P60. However, in the latter condition, which is reminiscent of MTLE, the
      hyperthermic seizures accelerated epileptogenesis and decreased the power in the
      high frequency gamma band, as well as decreasing the coherence between hippocampi
      and the involvement of the contralateral hippocampus during hippocampal
      paroxysmal discharges. Our data suggest that a single episode of prolonged
      hyperthermic seizures does not induce per se, but accelerates epileptogenesis and
      could lead to an asymmetrical dysfunction in the hippocampal rhythmicity in both
      physiological and pathological conditions. 

PMID- 24874547
TI  - Sex-specific consequences of early life seizures.
AB  - Seizures are very common in the early periods of life and are often associated
      with poor neurologic outcome in humans. Animal studies have provided evidence
      that early life seizures may disrupt neuronal differentiation and connectivity,
      signaling pathways, and the function of various neuronal networks. There is
      growing experimental evidence that many signaling pathways, like GABAA receptor
      signaling, the cellular physiology and differentiation, or the functional
      maturation of certain brain regions, including those involved in seizure control,
      mature differently in males and females. However, most experimental studies of
      early life seizures have not directly investigated the importance of sex on the
      consequences of early life seizures. The sexual dimorphism of the developing
      brain raises the question that early seizures could have distinct effects in
      immature females and males that are subjected to seizures. We will first discuss
      the evidence for sex-specific features of the developing brain that could be
      involved in modifying the susceptibility and consequences of early life seizures.
      We will then review how sex-related biological factors could modify the age
      specific consequences of induced seizures in the immature animals. These include
      signaling pathways (e.g., GABAA receptors), steroid hormones, growth factors.
      Overall, there are very few studies that have specifically addressed seizure
      outcomes in developing animals as a function of sex. The available literature
      indicates that a variety of outcomes (histopathological, behavioral, molecular,
      epileptogenesis) may be affected in a sex-, age-, region-specific manner after
      seizures during development. Obtaining a better understanding for the gender
      related mechanisms underlying epileptogenesis and seizure comorbidities will be
      necessary to develop better gender and age appropriate therapies. 

PMID- 24874546
TI  - A novel de novo mutation of SCN8A (Nav1.6) with enhanced channel activation in a
      child with epileptic encephalopathy.
AB  - Rare de novo mutations of sodium channels are thought to be an important cause of
      sporadic epilepsy. The well established role of de novo mutations of sodium
      channel SCN1A in Dravet Syndrome supports this view, but the etiology of many
      cases of epileptic encephalopathy remains unknown. We sought to identify the
      genetic cause in a patient with early onset epileptic encephalopathy by whole
      exome sequencing of genomic DNA. The heterozygous mutation c. 2003C>T in SCN8A,
      the gene encoding sodium channel Nav1.6, was detected in the patient but was not
      present in either parent. The resulting missense substitution, p.Thr767Ile,
      alters an evolutionarily conserved residue in the first transmembrane segment of
      channel domain II. The electrophysiological effects of this mutation were
      assessed in neuronal cells transfected with mutant or wildtype cDNA. The mutation
      causes enhanced channel activation, with a 10mV depolarizing shift in voltage
      dependence of activation as well as increased ramp current. In addition,
      pyramidal hippocampal neurons expressing the mutant channel exhibit increased
      spontaneous firing with PDS-like complexes as well as increased frequency of
      evoked action potentials. The identification of this new gain-of-function
      mutation of Nav1.6 supports the inclusion of SCN8A as a causative gene in
      infantile epilepsy, demonstrates a novel mechanism for hyperactivity of Nav1.6,
      and further expands the role of de novo mutations in severe epilepsy. 

PMID- 24874549
TI  - Characteristics of older at-risk drinkers who drive after drinking and those who
      do not drive after drinking.
AB  - OBJECTIVE: To describe and compare characteristics of older adults who drive
      after drinking and those who do not, whether an intervention addressing at-risk
      drinking reduces risk among those reporting driving after drinking, and reasons
      reported for driving after drinking. METHODS: Secondary data analysis of a
      randomized trial testing the efficacy of a multifaceted intervention to reduce at
      risk drinking among adults with a mean age of 68 years in primary care (N = 631).
      RESULTS: Almost a quarter of at-risk drinkers reported driving after drinking (N
      = 154). Compared to those who did not drive after drinking, those who did were
      more likely to be younger, male, and working. They consumed a higher average
      number of drinks per week, had more reasons they were considered at-risk
      drinkers, and were more likely to meet at-risk drinking criteria due to amount of
      drinking and binge drinking. Those driving after drinking at baseline reduced the
      frequency of this behavior at 3 and 12 months and there were no statistically
      significant differences in the proportions of persons still engaging in driving
      after drinking among those who were assigned to intervention or control groups.
      Reasons for driving after drinking included not thinking that it was a problem
      and having to get home. CONCLUSIONS: Driving after drinking is common in this
      population of older, at-risk drinkers recruited in primary care settings and,
      like younger adults, men and those reporting binge drinking are more likely to
      engage in this behavior. Given that this behavior is dangerous and the population
      of older adults is fast growing, interventions addressing driving after drinking
      are needed.

PMID- 24874550
TI  - User experience while viewing stereoscopic 3D television.
AB  - 3D display technologies have been linked to visual discomfort and fatigue. In a
      lab-based study with a between-subjects design, 433 viewers aged from 4 to 82
      years watched the same movie in either 2D or stereo 3D (S3D), and subjectively
      reported on a range of aspects of their viewing experience. Our results suggest
      that a minority of viewers, around 14%, experience adverse effects due to viewing
      S3D, mainly headache and eyestrain. A control experiment where participants
      viewed 2D content through 3D glasses suggests that around 8% may report adverse
      effects which are not due directly to viewing S3D, but instead are due to the
      glasses or to negative preconceptions about S3D (the 'nocebo effect'). Women were
      slightly more likely than men to report adverse effects with S3D. We could not
      detect any link between pre-existing eye conditions or low stereoacuity and the
      likelihood of experiencing adverse effects with S3D. 

PMID- 24874551
TI  - Overexpression of Dmp1 fails to rescue the bone and dentin defects in Fam20C
      knockout mice.
AB  - FAM20C is a kinase phosphorylating the small-integrin-binding ligand, N-linked
      glycoproteins (SIBLINGs), a group of extracellular matrix proteins that are
      essential for bone and dentin formation. Previously, we showed that Sox2
      Cre;Fam20Cfl/fl mice had bone and dentin defects, along with hypophosphatemia and
      significant downregulation of dentin matrix protein 1 (DMP1). While the assumed
      phosphorylation failure of the SIBLINGs is likely associated with the defects in
      the Fam20C-deficient mice, it remains unclear if the downregulation of Dmp1
      contributes to these phenotypes. In this study, we crossed 3.6 kb Col1-Dmp1
      transgenic mice with 3.6 kb Col1-Cre;Fam20Cfl/fl mice to overexpress Dmp1 in the
      mineralized tissues of Fam20C conditional knockout (cKO) mice. X-ray, micro
      computed tomography, serum biochemistry and histology analyses showed that
      expressing the Dmp1 transgene failed to rescue the bone and dentin defects, as
      well as the serum levels of FGF23 and phosphate in the Fam20C-cKO mice. These
      results indicated that the downregulation of Dmp1 may not directly associate
      with, or significantly contribute to the bone and dentin defects in the Fam20C
      cKO mice.

PMID- 24874552
TI  - The effects of platelet-rich plasma on the osteogenic induction of bone marrow
      mesenchymal stem cells.
AB  - Bone marrow mesenchymal stem cells (BMSCs) are multipotent stem cells. Finding
      methods to improve the osteogenic potential of these cells is a key factor in
      bone tissue engineering. Platelet-rich plasma (PRP) contains powerful growth
      factors that produce changes in a variety of cell types. The purpose of this
      study was to explore the effects of PRP on the osteogenic differentiation of
      BMSCs in vitro. Rabbit BMSCs were harvested and cultured in vitro in control
      media or in media enhanced with PRP. BMSCs began to attach 12-24 hours after
      seeding. A MTT assay demonstrated that PRP-induced BMSCs grew rapidly compared
      with the control group. The PRP group also showed strongly positive staining of
      alkaline phosphatase and mineralized nodules whereas the control group showed
      negative staining. However, the alkaline phosphatase activity and the mRNA level
      of the osteogenic markers (osteocalcin and osteopontin) remained higher in the
      PRP group. These results confirmed that PRP could enhance the proliferation of
      BMSCs and effectively promote the osteogenic differentiation of BMSCs in vitro.

PMID- 24874553
TI  - Localization of luteinizing hormone receptor protein in the human ovary.
AB  - The luteinizing hormone receptor (LHR) plays a pivotal role during follicular
      development. Consequently, its expression pattern is of major importance for
      research and has clinical implications. Despite the accumulated information
      regarding LHR expression patterns, our understanding of its expression in the
      human ovary, specifically at the protein level, is incomplete. Therefore, our aim
      was to determine the LHR protein localization and expression pattern in the human
      ovary. We examined the presence of LHR by immunohistochemical staining of human
      ovaries and western blots of mural granulosa and cumulus cells aspirated during
      IVF treatments. We were not able to detect LHR protein staining in primordial or
      primary follicles. We observed equivocal positive staining in granulosa cells and
      theca cells of secondary follicles. The first appearance of a clear signal of LHR
      protein was observed in granulosa cells and theca cells of small antral
      follicles, and there was evidence of increasing LHR production as the follicles
      mature to the pre-ovulatory stage. After ovulation, LHR protein was ubiquitously
      produced in the corpus luteum. To confirm the expression pattern in granulosa
      cells and cumulus cells, we performed western blots and found that LHR expression
      was stronger in granulosa cells than in cumulus cells, with the later
      demonstrating low, but still significant, amounts of LHR protein. In summary, we
      conclude that LHR protein starts to appear on granulosa cells and theca cells of
      early antral follicles, and low but significant expression of LHR exists also in
      the cumulus cells. These results may have implications for the future design of
      clinical protocols and culture mediums for in vitro fertilization and especially
      in vitro maturation of oocytes. 

PMID- 24874548
TI  - Nuclear receptors in neurodegenerative diseases.
AB  - Nuclear receptors have generated substantial interest in the past decade as
      potential therapeutic targets for the treatment of neurodegenerative disorders.
      Despite years of effort, effective treatments for progressive neurodegenerative
      diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease
      and ALS remain elusive, making non-classical drug targets such as nuclear
      receptors an attractive alternative. A substantial literature in mouse models of
      disease and several clinical trials have investigated the role of nuclear
      receptors in various neurodegenerative disorders, most prominently AD. These
      studies have met with mixed results, yet the majority of studies in mouse models
      report positive outcomes. The mechanisms by which nuclear receptor agonists
      affect disease pathology remain unclear. Deciphering the complex signaling
      underlying nuclear receptor action in neurodegenerative diseases is essential for
      understanding this variability in preclinical studies, and for the successful
      translation of nuclear receptor agonists into clinical therapies. 

PMID- 24874555
TI  - Investigating the effect of respiratory bodily threat on the processing of
      emotional pictures.
AB  - It has been demonstrated that emotions can substantially impact the perception
      and neural processing of breathlessness, but little is known about the reverse
      interaction. Here, we examined the impact of breathlessness on emotional picture
      processing. The continuous EEG was recorded while volunteers viewed
      positive/neutral/negative emotional pictures under conditions of resistive-load
      induced breathlessness, auditory noise, and an unloaded baseline. Breathlessness
      attenuated P1 and early posterior negativity (EPN) ERP amplitudes, irrespective
      of picture valence. Moreover, as expected, larger amplitudes for positive and
      negative pictures relative to neutral pictures were found for EPN and the late
      positive potential (LPP) ERPs, which were not affected by breathlessness. The
      results suggest that breathlessness impacts on the early attention-related neural
      processing of picture stimuli without influencing the later cognitive processing
      of emotional contents. 

PMID- 24874554
TI  - A role for the mitochondrial-associated protein p32 in regulation of trophoblast
      proliferation.
AB  - p32 is a conserved eukaryotic protein which is primarily expressed in the
      mitochondria and regulates cell proliferation, migration and metabolism in
      various tissues. In this study, we sought to examine the expression and function
      of p32 in the human placenta. p32 was highly expressed in the
      syncytiotrophoblast, the underlying cytotrophoblast (CTB), the vascular
      endothelium and by a proportion of cells in the villous stroma in first trimester
      and term placenta. p32 mRNA and protein expression was significantly higher in
      the first trimester of pregnancy than at term, and expression in the trophoblast
      was significantly reduced in placentas from women with fetal growth restriction
      (FGR). Small interfering RNA (siRNA)-mediated knockdown of p32 in term placental
      explants significantly reduced the number of Ki67-positive CTB, but did not alter
      CTB apoptosis or necrosis. p32 knockdown increased lactate production, reduced
      glucose extraction from culture medium and was associated with reduced
      MitoTracker dye accumulation in trophoblast mitochondria. p32 knockdown was also
      associated with a significant reduction in expression of the mitochondrial
      respiratory complexes I and IV. These data suggest that p32 expression is
      important for CTB proliferation, via a mechanism involving regulation of normal
      mitochondrial function. As p32 expression is reduced in FGR placentas, this may
      contribute to some of the observed placental pathology, such as reduced CTB
      proliferation and mitochondrial dysfunction. 

PMID- 24874556
TI  - Effects of prolonged lung inflation or deflation on pulmonary stretch receptor
      discharge in the alligator (Alligator mississippiensis).
AB  - The American alligator (Alligator mississippiensis) is a semi-aquatic diving
      reptile that has a periodic breathing pattern. Previous work identified pulmonary
      stretch receptors, that are rapidly and slowly adapting, as well as
      intrapulmonary chemoreceptors (IPC), sensitive to CO2, that modulate breathing
      patterns in alligators. The purpose of the present study was to quantify the
      effects of prolonged lung inflation and deflation (simulated dives) on pulmonary
      stretch receptors (PSR) and/or IPC discharge characteristics. The effects of
      airway pressure (0-20 cm H2O), hypercapnia (7% CO2), and hypoxia (5% O2) on
      dynamic and static responses of PSR were studied in juvenile alligators (mean
      mass=246 g) at 24 degrees C. Alligators were initially anesthetized with
      isoflurane, cranially pithed, tracheotomized and artificially ventilated. Vagal
      afferent tonic and phasic activity was recorded with platinum hook electrodes.
      Receptor activity was a mixture of slowly adapting PSR (SAR) and rapidly adapting
      PSR (RAR) with varying thresholds and degrees of adaptation, without CO2
      sensitivity. Receptor activity before, during and after 1 min periods of lung
      inflation and deflation was quantified to examine the effect of simulated breath
      hold dives. Some PSR showed a change in dynamic response, exhibiting inhibition
      for several breaths after prolonged lung inflation. Following 1 min deflation,
      RAR, but not SAR, exhibited a significant potentiation of burst frequency
      relative to control. For SAR, the post-inflation receptor inhibition was blocked
      by CO2 and hypoxia; for RAR, the post-inflation inhibition was potentiated by CO2
      and blocked by hypoxia. These results suggest that changes in PSR firing
      following prolonged inflation and deflation may promote post-dive ventilation in
      alligators. We hypothesize that PSR in alligators may be involved in recovery of
      breathing patterns and lung volume during pre- and post-diving behavior and
      apneic periods in diving reptiles.

PMID- 24874557
TI  - Intermittent hypercapnia enhances CO2 responsiveness and overcomes serotonergic
      dysfunction.
AB  - Serotonergic dysfunction compromises ventilatory chemosensitivity and may enhance
      vulnerability to pathologies such as the Sudden Infant Death Syndrome (SIDS). We
      have shown raphe contributions to central chemosensitivity involving serotonin (5
      HT)-and gamma-aminobutyric acid (GABA)-mediated mechanisms. We tested the
      hypothesis that mild intermittent hypercapnia (IHc) induces respiratory
      plasticity, due in part to strengthening of GABA mechanisms. Rat pups were IHc
      pretreated (eight consecutive cycles; 5 min 5% CO2 - air, 10 min air) or constant
      normocapnia-pretreated as a control, each day for 5 consecutive days beginning at
      P12. We subsequently assessed CO2 responsiveness using the in situ perfused
      brainstem preparation. Hypercapnic responses were determined with and without
      pharmacological manipulation. Results show IHc-pretreatment induces plasticity
      sufficient for responsiveness despite removal of otherwise critical ketanserin
      sensitive mechanisms. Responsiveness following IHc-pretreatment was absent if
      ketanserin was combined with GABAergic antagonism, indicating that plasticity
      depends on GABAergic mechanisms. We propose that IHc-induced plasticity could
      reduce the severity of reflex dysfunctions underlying pathologies such as SIDS.

PMID- 24874558
TI  - Lost in the jungle: new hurdles for optic nerve axon regeneration.
AB  - The poor regenerative capacity of injured central nervous system (CNS) axons
      leads to permanent neurological deficits after brain, spinal cord, or optic nerve
      lesions. In the optic nerve, recent studies showed that stimulation of the
      cytokine or mammalian target of rapamycin (mTOR) signaling pathways potently
      enhances sprouting and regeneration of injured retinal ganglion cell axons in
      adult mice, but does not allow the majority of axons to reach their main cerebral
      targets. New analyses have revealed axon navigation defects in the optic nerve
      and at the optic chiasm under conditions of strong growth stimulation. We propose
      that a balanced growth stimulatory treatment will have to be combined with
      guidance factors and suppression of local growth inhibitory factors to obtain the
      full regeneration of long CNS axonal tracts. 

PMID- 24874559
TI  - A synthesis and crystal chemical study of the fast ion conductor Li(7-3x)Ga(x)La3
      Zr2O12 with x = 0.08 to 0.84.
AB  - Fast-conducting phase-pure cubic Ga-bearing Li7La3Zr2O12 was obtained using solid
      state synthesis methods with 0.08 to 0.52 Ga(3+) pfu in the garnet. An upper
      limit of 0.72 Ga(3+) pfu in garnet was obtained, but the synthesis was
      accompanied by small amounts of La2Zr2O12 and LiGaO3. The synthetic products were
      characterized by X-ray powder diffraction, electron microprobe and SEM analyses,
      ICP-OES measurements, and (71)Ga MAS NMR spectroscopy. The unit-cell parameter,
      a0, of the various garnets does not vary significantly as a function of Ga(3+)
      content, with a value of about 12.984(4) A. Full chemical analyses for the solid
      solutions were obtained giving: Li7.08Ga0.06La2.93Zr2.02O12,
      Li6.50Ga0.15La2.96Zr2.05O12, Li6.48Ga0.23La2.93Zr2.04O12,
      Li5.93Ga0.36La2.94Zr2.01O12, Li5.38Ga0.53La2.96Zr1.99O12,
      Li4.82Ga0.60La2.96Zr2.00O12, and Li4.53Ga0.72La2.94Zr1.98O12. The NMR spectra are
      interpreted as indicating that Ga(3+) mainly occurs in a distorted 4-fold
      coordinated environment that probably corresponds to the general 96h
      crystallographic site of garnet. 

PMID- 24874560
TI  - Decreased placental thickness and impaired Doppler indices in idiopathic
      polyhydramnios: a prospective case-control study.
AB  - OBJECTIVE: To evaluate placental thickness, Doppler velocimetry, biophysical
      profile and perinatal outcomes in pregnancies complicated by idiopathic
      polyhydramnios. MATERIALS AND METHODS: This prospective case-control study was
      conducted on 139 pregnant women, of these 70 patients with idiopathic
      polyhydramnios comprised the study group and 60 pregnant women comprised the
      control group. Risk factors recorded were; age, parity, body mass index (BMI),
      gestational weeks, amniotic fluid index (AFI), biophysical profiles (BPP),
      placental thickness, middle cerebral artery pulsatility index (MCA PI), umbilical
      artery Doppler velocimetry (Umb A S/D) values and perinatal outcomes. RESULTS:
      Sixty-nine of the cases had mild-moderate (AFI: 250-450 mm) polyhydramnios
      (%98.5) and one of the cases had severe polyhydramnios (>450 mm) in study group.
      There was no statistically significant difference between the groups in terms of
      age, parity, BMI, gestational weeks, fetal birth weights and BPP (p > 0.05).
      Placental thickness, MCA PI and UA S/D values showed statistically significant
      difference between the groups (p < 0.05). The fetuses with lower placental
      thickness had lower scores of biophysical profile. There were negative
      correlations between placental thickness and AFI (r = -0.265), umbilical artery
      S/D and placental thickness (r = -0.212), MCA PI and AFI (r = -171, p = 0.44).
      However there was a positive correlation between AFI and umbilical artery Doppler
      values (r = 0.450). CONCLUSION: Idiopathic polyhydramnios is associated with
      decreased placental thickness, impaired uterine, umbilical and middle cerebral
      artery flow.

PMID- 24874561
TI  - Systematic use of the RAM nasal cannula in the Yale-New Haven Children's Hospital
      Neonatal Intensive Care Unit: a quality improvement project.
AB  - OBJECTIVE: To evaluate the clinical efficacy of the RAM nasal cannula (NC) with
      different modes of non-invasive ventilation (NIV) in the neonatal intensive care
      unit (NICU). METHODS: A single center prospective, observational study of infants
      placed on RAM NC. A small trial (Study 1) was completed in 16 infants on NIV via
      the RAM NC over a 48-h period to create Summary Statement recommendations. Next,
      over a 10-month period (Study 2), data were prospectively collected for the
      outcome of all infants receiving respiratory support with the RAM NC. Outcomes
      were compared between different modes of NIV and whether the recommendations were
      followed. RESULTS: The Study 2 population consisted of 88 infants of whom 67
      infants received nasal continuous positive airway pressure ventilation (NCPAP)
      and 21 received nasal intermittent positive pressure ventilation (NIPPV) via the
      RAM NC. The NIPPV group tended to be younger, smaller and stayed on the RAM NC
      longer. The overall success rate in weaning off the RAM NC, if our guidelines
      were followed, was 63%. CONCLUSION: RAM NC use with NIV was well tolerated in the
      neonatal population with the use of our guidelines. We speculate that use of our
      guidelines will lead to a more systematic use of the RAM NC in the NICU.

PMID- 24874563
TI  - Methylocella: a gourmand among methanotrophs.
AB  - A recent article in Nature describes the ability of Methylocella silvestris to
      grow simultaneously on methane and longer chain alkanes, something never before
      observed in the microbial world. It adds to a growing list of unique metabolic
      traits that distinguish Methylocella from any other bacterium. 

PMID- 24874564
TI  - Second meal effect on appetite and fermentation of wholegrain rye foods.
AB  - BACKGROUND: Wholegrain rye has been associated with decreased hunger sensations.
      This may be partly mediated by colonic fermentation. Sustained consumption of
      fermentable components is known to change the gut microflora and may increase
      numbers of saccharolytic bacteria. OBJECTIVE: To investigate the effect of
      wholegrain rye consumption on appetite and colonic fermentation after a
      subsequent meal. METHODS: In a randomized, controlled, three-arm cross-over
      study, twelve healthy male subjects consumed three iso-caloric evening test
      meals. The test meals were based on white wheat bread (WBB), wholegrain rye
      kernel bread (RKB), or boiled rye kernels (RK). Breath hydrogen excretion and
      subjective appetite sensation were measured before and at 30 min intervals for 3
      h after a standardized breakfast in the subsequent morning. After the 3 h, an ad
      libitum lunch meal was served to assess energy intake. In an in vitro study, RKB
      and RK were subjected to digestion and 24 h-fermentation in order to study SCFA
      production and growth of selected saccharolytic bacteria. RESULTS: The test meals
      did not differ in their effect on parameters of subjective appetite sensation the
      following day. Ad libitum energy intake at lunch was, however, reduced by 11% (P
      < 0.01) after RKB and 7% (P < 0.05) after RK compared with after WWB evening
      meal. Breath hydrogen excretion was significantly increased following RKB and RK
      evening meals compared with WWB (P < 0.01 and P < 0.05, respectively). Overall,
      RKB and RK were readily fermented in vitro and exhibited similar fermentation
      profiles, although total SCFA production was higher for RK compared with RKB (P <
      0.001). In vitro fermentation of RKB and RK both increased the relative
      quantities of Bifidobacterium and decreased Bacteroides compared with inoculum (P
      < 0.001). The C. coccoides group was reduced after RKB (P < 0.001). CONCLUSION:
      Consumption of wholegrain rye products reduced subsequent ad libitum energy
      intake in young healthy men, possibly mediated by mechanisms related to colonic
      fermentation.

PMID- 24874567
TI  - Tailoring the LCST of thermosensitive hydrogel thin films deposited by iCVD.
AB  - Using the iCVD (initiated chemical vapor deposition) polymerization technique, we
      generated a library of thermosensitive thin film hydrogels in the physiological
      temperature range. The library shows how a specific hydrogel with a desired
      temperature response can be synthesized via the copolymerization of three main
      components: (a) the main thermosensitive monomer, which determines the
      temperature range of the LCST; (b) the comonomer, which modulates the temperature
      according to its hydrophilic/hydrophobic behavior; and (c) the cross-linker,
      which determines the swelling degree and the polymer chain mobility of the
      resulting hydrogel. The thermosensitive thin films included in the library have
      been characterized by the water contact angle (WCA), revealing a switchable
      hydrophobic/hydrophilic behavior depending on the temperature and a decrease in
      the WCA with the incorporation of hydrophilic moieties. Moreover, a more accurate
      characterization by quartz crystal microbalance (QCM) is performed. With
      temperature and flow control, the switchable swelling properties of the
      thermosensitive thin films (due to the polymer mixture transition) can be
      recorded and analyzed in order to study the effects of the comonomer moieties on
      the lower critical solution temperature (LCST). Thus, the LCST tailoring method
      has been successfully used in this paper, and thermoresponsive thin films (50 nm
      in thickness) have been deposited by iCVD, exhibiting LCSTs in the 32-49  degrees
      C range. Due to the presented method's ability to tailor the LCST in the
      physiological temperature range, the developed thermoresponsive films present
      potential biosensing and drug delivery applications in the biomedical field. 

PMID- 24874565
TI  - Bran fibers and satiety in women who do not exhibit restrained eating.
AB  - BACKGROUND: Foods that are high in dietary fiber can promote satiety, but
      previous studies report conflicting results. OBJECTIVE: The objective was to
      determine differences in satiety response to three conditions (10 g oat bran, 10
      g barley bran and a low fiber condition) consumed at dinner and breakfast. In
      addition, we compared energy intake at an ad libitum lunch after consumption of
      the breakfast bars. DESIGN: Randomized, double-blind crossover study.
      PARTICIPANTS/SETTING: 42 normal weight women. INTERVENTION: Women consumed a
      dinner food bar from one of the three conditions the evening before testing. On
      test mornings, fasted women consumed the corresponding breakfast food bar with
      their choice of coffee, tea or water. An ad libitum pizza lunch was served 4
      hours after breakfast. PRIMARY OUTCOMES: Visual analogue scales (VAS) were used
      to assess satiety at baseline, 15, 30, 45, 60, 90, 120, 180 and 240 minutes.
      Energy intake was assessed by an ad libitum pizza lunch (4 hours after breakfast)
      and 24-hour energy intake was measured by a food diary. STATISTICAL ANALYSES:
      Treatments were compared using the mixed-effects linear models. Outcomes are
      reported as mean +/- SEM. RESULTS: There were no significant differences among
      conditions on any of the satiety scales and no significant differences among
      conditions in energy consumed at lunch or over 24 hours. The fiber bars were well
      tolerated and no significant differences were found for gastrointestinal
      tolerance. CONCLUSIONS: Our results do not support an effect of bran fibers on
      satiety above a low fiber control. We acknowledge results of this study may be
      intricately tied to the choice of a single pizza lunch, as other ad libitum meal
      options could have resulted in different outcomes.

PMID- 24874566
TI  - Variability in costs across hospital wards. A study of Chinese hospitals.
AB  - INTRODUCTION: Analysts estimating the costs or cost-effectiveness of health
      interventions requiring hospitalization often cut corners because they lack data
      and the costs of undertaking full step-down costing studies are high. They
      sometimes use the costs taken from a single hospital, sometimes use simple rules
      of thumb for allocating total hospital costs between general inpatient care and
      the outpatient department, and sometimes use the average cost of an inpatient bed
      day instead of a ward-specific cost. PURPOSE: In this paper we explore for the
      first time the extent and the causes of variation in ward-specific costs across
      hospitals, using data from China. We then use the resulting model to show how
      ward-specific costs for hospitals outside the data set could be estimated using
      information on the determinants identified in the paper. METHODOLOGY: Ward
      specific costs estimated using step-down costing methods from 41 hospitals in 12
      provinces of China were used. We used seemingly unrelated regressions to identify
      the determinants of variability in the ratio of the costs of specific wards to
      that of the outpatient department, and explain how this can be used to generate
      ward-specific unit costs. FINDINGS: Ward-specific unit costs varied considerably
      across hospitals, ranging from 1 to 24 times the unit cost in the outpatient
      department--average unit costs are not a good proxy for costs at specialty wards
      in general. The most important sources of variability were the number of staff
      and the level of capacity utilization. PRACTICE IMPLICATIONS: More careful
      hospital costing studies are clearly needed. In the meantime, we have shown that
      in China it is possible to estimate ward-specific unit costs taking into account
      key determinants of variability in costs across wards. This might well be a
      better alternative than using simple rules of thumb or using estimates from a
      single study.

PMID- 24874569
TI  - TCGA-assembler: open-source software for retrieving and processing TCGA data.

PMID- 24874568
TI  - Adaptation of a cyanobacterium to a biochemically rich environment in
      experimental evolution as an initial step toward a chloroplast-like state.
AB  - Chloroplasts originated from cyanobacteria through endosymbiosis. The original
      cyanobacterial endosymbiont evolved to adapt to the biochemically rich
      intracellular environment of the host cell while maintaining its photosynthetic
      function; however, no such process has been experimentally demonstrated. Here, we
      show the adaptation of a model cyanobacterium, Synechocystis sp. PCC 6803, to a
      biochemically rich environment by experimental evolution. Synechocystis sp. PCC
      6803 does not grow in a biochemically rich, chemically defined medium because
      several amino acids are toxic to the cells at approximately 1 mM. We cultured the
      cyanobacteria in media with the toxic amino acids at 0.1 mM, then serially
      transferred the culture, gradually increasing the concentration of the toxic
      amino acids. The cells evolved to show approximately the same specific growth
      rate in media with 0 and 1 mM of the toxic amino acid in approximately 84
      generations and evolved to grow faster in the media with 1 mM than in the media
      with 0 mM in approximately 181 generations. We did not detect a statistically
      significant decrease in the autotrophic growth of the evolved strain in an
      inorganic medium, indicating the maintenance of the photosynthetic function.
      Whole-genome resequencing revealed changes in the genes related to the cell
      membrane and the carboxysome. Moreover, we quantitatively analyzed the
      evolutionary changes by using simple mathematical models, which evaluated the
      evolution as an increase in the half-maximal inhibitory concentration (IC50) and
      estimated quantitative characteristics of the evolutionary process. Our results
      clearly demonstrate not only the potential of a model cyanobacterium to adapt to
      a biochemically rich environment without a significant decrease in photosynthetic
      function but also the properties of its evolutionary process, which sheds light
      of the evolution of chloroplasts at the initial stage. 

PMID- 24874570
TI  - Multicolor two-photon light-sheet microscopy.

PMID- 24874571
TI  - A simple image correction method for high-throughput microscopy.

PMID- 24874572
TI  - KinomeXplorer: an integrated platform for kinome biology studies.

PMID- 24874573
TI  - Models: stretching the skills of cell lines and mice.

PMID- 24874574
TI  - Of (stressed) mice and men.

PMID- 24874576
TI  - Si-H and Si-C bond cleavage reactions of silane and phenylsilanes with Mo(PMe3)6:
      silyl, hypervalent silyl, silane, and disilane complexes.
AB  - Mo(PMe3)6 cleaves the Si-H bonds of SiH4, PhSiH3, and Ph2SiH2 to afford a variety
      of novel silyl, hypervalent silyl, silane, and disilane complexes, as
      respectively illustrated by Mo(PMe3)4(SiH3)2H2, Mo(PMe3)4(kappa(2)-H2-H2SiPh2H)H,
      Mo(PMe3)3(sigma-HSiHPh2)H4, and Mo(PMe3)3(kappa(2)-H2-H2Si2Ph4)H2.
      Mo(PMe3)4(kappa(2)-H2-H2SiPh2H)H and Mo(PMe3)3(kappa(2)-H2-H2Si2Ph4)H2 are
      respectively the first examples of complexes that feature a hypervalent kappa(2)
      H2-H2SiPh2H silyl ligand and a chelating disilane ligand, and both compounds
      convert to the diphenylsilane adduct, Mo(PMe3)3(sigma-HSiHPh2)H4, in the presence
      of H2. Mo(PMe3)4(SiH3)2H2 undergoes isotope exchange with SiD4, and NMR
      spectroscopic analysis of the SiHxD4-x isotopologues released indicates that the
      reaction does not occur via initial reductive elimination of SiH4, but rather by
      a metathesis pathway. 

PMID- 24874575
TI  - PADI4 acts as a coactivator of Tal1 by counteracting repressive histone arginine
      methylation.
AB  - The transcription factor Tal1 is a critical activator or repressor of gene
      expression in hematopoiesis and leukaemia. The mechanism by which Tal1
      differentially influences transcription of distinct genes is not fully
      understood. Here we show that Tal1 interacts with the peptidylarginine deiminase
      IV (PADI4). We demonstrate that PADI4 can act as an epigenetic coactivator
      through influencing H3R2me2a. At the Tal1/PADI4 target gene IL6ST the repressive
      H3R2me2a mark triggered by PRMT6 is counteracted by PADI4, which augments the
      active H3K4me3 mark and thus increases IL6ST expression. In contrast, at the CTCF
      promoter PADI4 acts as a repressor. We propose that the influence of PADI4 on
      IL6ST transcription plays a role in the control of IL6ST expression during
      lineage differentiation of hematopoietic stem/progenitor cells. These results
      open the possibility to pharmacologically influence Tal1 in leukaemia. 

PMID- 24874577
TI  - Modeling the efficiency of a magnetic needle for collecting magnetic cells.
AB  - As new magnetic nanoparticle-based technologies are developed and new target
      cells are identified, there is a critical need to understand the features
      important for magnetic isolation of specific cells in fluids, an increasingly
      important tool in disease research and diagnosis. To investigate magnetic cell
      collection, cell-sized spherical microparticles, coated with superparamagnetic
      nanoparticles, were suspended in (1) glycerine-water solutions, chosen to
      approximate the range of viscosities of bone marrow, and (2) water in which 3, 5,
      10 and 100% of the total suspended microspheres are coated with magnetic
      nanoparticles, to model collection of rare magnetic nanoparticle-coated cells
      from a mixture of cells in a fluid. The magnetic microspheres were collected on a
      magnetic needle, and we demonstrate that the collection efficiency versus time
      can be modeled using a simple, heuristically-derived function, with three
      physically-significant parameters. The function enables experimentally-obtained
      collection efficiencies to be scaled to extract the effective drag of the
      suspending medium. The results of this analysis demonstrate that the effective
      drag scales linearly with fluid viscosity, as expected. Surprisingly, increasing
      the number of non-magnetic microspheres in the suspending fluid results increases
      the collection of magnetic microspheres, corresponding to a decrease in the
      effective drag of the medium. 

PMID- 24874578
TI  - The effects of histone deacetylase inhibitors on glioblastoma-derived stem cells.
AB  - Glioblastoma multiforme (GBM) is the most malignant brain tumor with limited
      effective treatment options. Cancer stem cells (CSCs), a subpopulation of cancer
      cells with stem cell properties found in GBMs, have been shown to be extremely
      resistant to radiation and chemotherapeutic agents and have the ability to
      readily reform tumors. Therefore, the development of therapeutic agents targeting
      CSCs is extremely important. In this study, we isolated glioblastoma-derived stem
      cells (GDSCs) from GBM tissue removed from patients during surgery and analyzed
      their gene expression using quantitative real-time PCR and immunocytochemistry.
      We examined the effects of histone deacetylase inhibitors trichostatin A (TSA)
      and valproic acid (VPA) on the proliferation and gene expression profiles of
      GDSCs. The GDSCs expressed significantly higher levels of both neural and
      embryonic stem cell markers compared to GBM cells expanded in conventional
      monolayer cultures. Treatment of GDSCs with histone deacetylase inhibitors, TSA
      and VPA, significantly reduced proliferation rates of the cells and expression of
      the stem cell markers, indicating differentiation of the cells. Since
      differentiation into GBM makes them susceptible to the conventional cancer
      treatments, we posit that use of histone deacetylase inhibitors may increase
      efficacy of the conventional cancer treatments for eliminating GDSCs. 

PMID- 24874579
TI  - NAP reduces murine microvascular endothelial cells proliferation induced by
      hyperglycemia.
AB  - Hyperglycemia has been identified as a risk factor responsible for micro- and
      macrovascular complications in diabetes. NAP (Davunetide) is a peptide whose
      neuroprotective actions are widely demonstrated, although its biological role on
      endothelial dysfunctions induced by hyperglycemia remains uninvestigated. In the
      present study we hypothesized that NAP could play a protective role on
      hyperglycemia-induced endothelial cell proliferation. To this end we investigated
      the effects of NAP on an in vitro model of murine microvascular endothelial cells
      grown in high glucose for 7 days. The MTT (3-[4,5-dimethylthiazol-2-yl]-2,5
      diphenyltetrazolium bromide) assay and cyclin D1 protein expression analysis
      revealed that NAP treatment significantly reduces viability and proliferation of
      the cells. Hyperglycemia induced the activation of mitogen-activated protein
      kinase/extracellular signal-regulated protein kinase and/or phosphatidylinositol
      3 kinase/Akt pathways in a time-dependent manner. NAP treatment reduced the
      phosphorylation levels of ERK and AKT in cells grown in high glucose. These
      evidences suggest that NAP might be effective in the regulation of endothelial
      dysfunction induced by hyperglycemia.

PMID- 24874582
TI  - Toward the development of the potential with angular distortion for halogen bond:
      a comparison of potential energy surfaces between halogen bond and hydrogen bond.
AB  - As noncovalent intermolecular interactions, hydrogen bond (HB) and halogen bond
      (XB) are attracting increasing attention. In this work, the potential energy
      surfaces (PESs) of hydrogen and halogen bonds are compared. Twelve halogen-bonded
      and three hydrogen-bonded models are scanned for analysis using the MP2 level of
      theory. This work indicates that potential energy surfaces of both HB and XB have
      angular distortion. The potential well of XB is narrower than that of HB. With
      the elongation of the bond length, the potential energy surfaces get flatter. The
      best fitting functions for angular distortion and the flattening character of
      angular terms are also combined into a modified Buckingham potential. The testing
      results show that the essential features of the PES, including angular distortion
      and flattening character, have been reproduced. These results provide a better
      understanding of halogen and hydrogen bonds and the optimization of halogen bond
      force fields. 

PMID- 24874581
TI  - Downregulation of neuregulin 1-ErbB4 signaling and antidepressant properties of
      ketamine: ErbB4 expressing pyramidal neurons may play a role.
AB  - We comment on a recent paper of Wang et al. (J Mol Neurosci, 2014), who have
      shown that ketamine reduces neuregulin1-ErbB4 signaling in interneurons. 

PMID- 24874580
TI  - Investigation of the possible functions of PACAP in human trophoblast cells.
AB  - Pituitary adenylate cyclase activating polypeptide (PACAP) is an endogenous
      neuropeptide having a widespread distribution both in the nervous system and
      peripheral organs including the female reproductive system. Both the peptide and
      its receptors have been shown in the placenta but its role in placental growth,
      especially its human aspects, remains unknown. The aim of the present study was
      to investigate the effects of PACAP on invasion, proliferation, cell survival,
      and angiogenesis of trophoblast cells. Furthermore, cytokine production was
      investigated in human decidual and peripheral blood mononuclear cells. For in
      vitro studies, human invasive proliferative extravillous cytotrophoblast (HIPEC)
      cells and HTR-8/SVneo human trophoblast cells were used. Both cell types were
      used for testing the effects of PACAP on invasion and cell survival in order to
      investigate whether the effects of PACAP in trophoblasts depend on the examined
      cell type. Invasion was studied by standardized invasion assay. PACAP increased
      proliferation in HIPEC cells, but not in HTR-8 cells. Cell viability was examined
      using MTT test, WST-1 assay, and annexin V/propidium iodide flow cytometry assay.
      Survival of HTR-8/SVneo cells was studied under oxidative stress conditions
      induced by hydrogen peroxide. PACAP as pretreatment, but not as co-treatment,
      significantly increased the number of surviving HTR-8 cells. Viability of HIPEC
      cells was investigated using methotrexate (MTX) toxicity, but PACAP1-38 could not
      counteract its toxic effect. Angiogenic molecules were determined both in the
      supernatant and the cell lysate by angiogenesis array. In the supernatant, we
      found that PACAP decreased the secretion of various angiogenic markers, such as
      angiopoietin, angiogenin, activin, endoglin, ADAMTS-1, and VEGF. For the cytokine
      assay, human decidual and peripheral blood lymphocytes were separated and treated
      with PACAP1-38. Th1 and Th2 cytokines were analyzed with CBA assay and the
      results showed that there were no significant differences in control and PACAP
      treated cells. In summary, PACAP seems to play various roles in human trophoblast
      cells, depending on the cell type and microenvironmental influences. 

PMID- 24874583
TI  - Highly fluorinated hydrotris(indazolyl)borate calcium complexes: the structure
      and reactivity heavily depend on the ligand's electronic properties.
AB  - Two series of highly fluorinated 3-substituted hydrotris(indazolyl)borate (Fn
      Tp(4Bo,3R); R = Ph, n = 12; R = CF3, n = 21) complexes of calcium were
      synthesized by salt metathesis reactions. CaI2 reacts with 2 and 1 equiv. of
      Tl(F12-Tp(4Bo,3Ph)) in THF to form the homo- and heteroleptic complexes [Ca(F12
      Tp((4Bo,3Ph)*))2] (1) and [(F12-Tp(4Bo,3Ph))CaI(THF)] (2), respectively. 1 has
      C2h symmetry due to a 1,2-borotropic shift. The reaction of CaI2 with 2 equiv. of
      the more electron poor Tl(F21-Tp(4Bo,3CF3)) in THF, on the other hand, leads to
      the salt [Ca(THF)6][F21-Tp(4Bo,3CF3)]2 (3), with [F21-Tp(4Bo,3CF3)] acting as a
      counter-ion. This emphasizes the tuning ability of Fn-Tp(4Bo,3R) ligands and the
      consequences on their ability to bind hard electrophilic Ca(2+) centers. 

PMID- 24874588
TI  - Effects of surfactant on biofilm formation on silicone nasal splints.
AB  - Biofilms are sessile communities of bacteria embedded in self-produced
      extracellular polysaccharide matrix and are considered to be responsible for
      bacterial infections in humans. Topical surfactant use on silicone nasal splints
      may have a preventive effect on biofilm formation. The objective of this study is
      to investigate the effect of surfactant-containing nasal solutions on biofilm
      formation over the surface of silicone nasal splints. Forty patients were
      randomized after septoplasty to receive surfactant-containing saline solution
      (group 1) or saline without surfactant (group 2). At the postoperative 48th, 72th
      and 96th hours, pieces of splint samples were taken and prepared for scanning
      electron microscopic evaluation. Biofilm formation was observed in 3, 6 and 14 of
      20 samples in group 1 (surfactant used) and 3, 14 and 20 of 20 samples in group 2
      (control) at 48th, 72th and 96th hours, respectively. Biofilm formation
      incidences of groups at 48th hour were similar (p > 0.05), whereas it was
      significantly lower at group 1 regarding 72th and 96th hours (p < 0.05).
      Surfactant-containing nasal solutions have an inhibitory effect on biofilm
      formation over the surface of silicone nasal splints especially after 48 h.
      Surfactant-containing nasal solutions may have an important role in nasal septal
      dressing in the future.

PMID- 24874587
TI  - Prevalence, clinical profile, iron status, and subject-specific traits for
      excessive erythrocytosis in andean adults living permanently at 3,825 meters
      above sea level.
AB  - BACKGROUND: Excessive erythrocytosis (EE) is a prevalent condition in populations
      living at high altitudes (> 2,500 m above sea level). Few large population-based
      studies have explored the association between EE and multiple subject-specific
      traits including oxygen saturation, iron status indicators, and pulmonary
      function. METHODS: We enrolled a sex-stratified and age-stratified sample of
      1,065 high-altitude residents aged >= 35 years from Puno, Peru (3,825 m above sea
      level) and conducted a standardized questionnaire and physical examination that
      included spirometry, pulse oximetry, and a blood sample for multiple clinical
      markers. Our primary objectives were to estimate the prevalence of EE,
      characterize the clinical profile and iron status indicators of subjects with EE,
      and describe subject-specific traits associated with EE. RESULTS: Overall
      prevalence of EE was 4.5% (95% CI, 3.3%-6.0%). Oxygen saturation was
      significantly lower among EE than non-EE group subjects (85.3% vs 90.1%, P <
      .001) but no difference was found in iron status indicators between both groups
      (P > .09 for all values). In multivariable logistic regression, we found that age
      >= 65 years (OR = 2.45, 95% CI, 1.16-5.09), male sex (3.86, 1.78-9.08), having
      metabolic syndrome (2.66, 1.27-5.75) or being overweight (5.20, 1.95-16.77),
      pulse oximetry < 85% (14.90, 6.43-34.90), and % predicted FVC < 80% (13.62, 4.40
      41.80) were strongly associated with EE. Attributable fractions for EE were
      greatest for being overweight (26.7%), followed by male sex (21.5%), pulse
      oximetry < 85% (16.4%), having metabolic syndrome (14.4%), and % predicted FVC <
      80% (9.3%). CONCLUSIONS: We found a lower prevalence of EE than in previous
      reports in the Peruvian Andes. Although the presence of hypoxemia and decreased
      vital capacity were strongly associated with excessive erythrocytosis, being
      overweight or having metabolic syndrome were associated with an important
      fraction of cases in our study population.

PMID- 24874589
TI  - Automated optimization of photonic crystal slab cavities.
AB  - Thanks to their high quality factor, combined to the smallest modal volume,
      defect-cavities in photonic crystal slabs represent a promising, versatile tool
      for fundamental studies and applications in photonics. In paricular, the L3, H0,
      and H1 defects are the most popular and widespread cavity designs, due to their
      compactness, simplicity, and small mode volume. For these cavities, the current
      best optimal designs still result in Q-values of a few times 10(5) only, namely
      one order of magnitude below the bound set by fabrication imperfections and
      material absorption in silicon. Here, we use a genetic algorithm to find a global
      maximum of the quality factor of these designs, by varying the positions of few
      neighbouring holes. We consistently find Q-values above one million - one order
      of magnitude higher than previous designs. Furthermore, we study the effect of
      disorder on the optimal designs and conclude that a similar improvement is also
      expected experimentally in state-of-the-art systems. 

PMID- 24874590
TI  - Hypovitaminosis D in a sunny country: time trends, predictors, and implications
      for practice guidelines.
AB  - The aim of the current study is to investigate the prevalence of hypovitaminosis
      D in Lebanese subjects, its robust predictors, evaluate the relationship between
      25 hydroxy vitamin D [25(OH)D] and parathyroid hormone levels, and derive
      desirable vitamin D levels, based on a large hospital laboratory database
      spanning all age groups. Data from a large representative digitized database of
      9147 subjects, mostly outpatients, evaluated between 2000-2004 and 2007-2008, in
      whom information on age, gender, service, and time of the year, was analyzed. The
      PTH-25(OH)D relationship was studied in a subset of 657 adult subjects, in whom
      such data were available. At a 25(OH)D cut-off of<20 ng/ml, the prevalence of
      hypovitaminosis D ranged between 58% and 62% in pediatric subjects, 44% and 60%
      in adults, and 41% and 62% in elderly, in the 2 study periods. At a cut-off <30
      ng/ml, the prevalence was above 78%, in most sub-groups. Regardless of cut-off
      used, the only significant predictors of high mean 25(OH)D levels were the male
      gender in the pediatric group, and female gender in adults and elderly,
      summer/fall seasons, out-patient status, as well as study period. Curve fitting
      of the PTH-25(OH)D relationship, in adults and elderly, revealed a plateau at
      25(OH)D levels of 17-21 ng/ml, depending on sub-study group. Hypovitaminosis D is
      prevalent in our sunny country, even using a conservative population-derived cut
      off of 20 ng/ml, and thus the need for a public health strategy for
      supplementation.

PMID- 24874593
TI  - Morphological maturation and survival of chicken and rat embryonic neurons on
      different culture substrata.
AB  - Neuronal cells from chicken and rat embryonic cerebral hemispheres were plated at
      a low cell concentration and cultured either on collagen or on a supporting
      continuous glial layer for periods of up to 21 days. The glial layer was either
      homologous or heterologous with regard to the animal species; the survival and
      maturation of the neuronal cells in these different conditions were investigated
      by light and electron microscopy. Neuronal cells cultured on collagen formed
      aggregates similar to those formed by neuronal cells plated at high cell density
      as described in a previous paper; a few aggregated neurons formed processes after
      24 h and, only after 48 h of culture, more fibres had developed; the majority of
      the cells progressively degenerated between days 7 and 21 of culture. In contrast
      to this, neuronal cells cultured on a supporting glial layer, whether homologous
      or heterologous, progressively differentiated: neuronal perikarya remained well
      separated from each other and many processes were already formed after 24 h;
      later on, networks of fibres developed. At the electron microscopic level,
      microtubules and neurofilaments were present at a high density in the cells and
      fibres; immature synapses could be found, but infrequently. Differentiated cells
      were represented mostly by neurons; oligodendroglial cells were absent, and
      myelinated fibres could not be detected. The highest positive effect on the
      maturation and survival of neuronal cells was observed in the presence of a layer
      of glial cells from the same species. These results emphasize the essential role
      of glial cells for the neuronal maturation in the absence of contact between
      neuroblasts. 

PMID- 24874592
TI  - Rat brain glycosyltransferase activities during postnatal development.
AB  - Enzymatic activity of seven glycoprotein and glycolipid glycosyltransferases was
      studied in microsomal fractions during postnatal development of rat brain from 3
      to 42 days after birth. Specific enzymatic variations were detected for some
      glycosyltransferases, i.d. a maxima was shown at 7 days post partum for the
      glycoprotein galactosyltransferase and another one at 21 days for
      galactosylceramide biosynthesis, this latter correlated to myelin synthesis.
      However, a regular and important activity maxima was always detected for six of
      the enzymes studied (asialofetuin fucosyltransferase, ovomucoid
      galactosyltransferase, dolichyl phosphate mannose synthase, ceramide,
      galactosylceramide and glucosylceramide galactosyltransferases) at the period
      from 35 to 40 days post partum. As this period corresponds to immediate post
      puberty, an endocrinoneuronal control of the glycosyltransferases by sexual
      hormones is suggested. 

PMID- 24874594
TI  - Nicotinic acetylcholine receptor from foetal human skeletal muscle.
AB  - Nicotinic acetylcholine receptor protein has been purified from foetal and adult
      skeletal muscle by extraction in non-ionic detergent followed by purification on
      immobilised alpha-toxin. Purified foetal and adult receptors focused as single,
      sharp peaks whether directly labelled with (125)I or indirectly labelled with
      (125)I-alpha-bungarotoxin. Polyacrylamide gel electrophoresis of the purified
      foetal and adult receptors each showed four major protein bands with Mr 44,000,
      51,000, 58,000 and 66,000; only that with Mr 44,000 was, in each case, labelled
      with the affinity reagent, 4-(N-maleimido) [(3)H]benzyltrimethylammonium. When
      the four major subunits, obtained by polyacrylamide gel electrophoresis, were
      labelled with (125)I-ConA, markedly different patterns of radioactivity were
      shown by the foetal and adult receptors, the band at 44,000 being less heavily
      labelled in the foetal case. Foetal and adult receptors behaved similarly with
      respect to inhibition by ConA of binding of (125)I-alpha-bungarotoxin; inhibition
      in both cases reaching a maximum of 70%. Foetal and adult receptors each showed
      single (125)I-alpha-bungarotoxin binding species in sucrose density gradient
      centrifugation with S20w = 8.5Sand 9.5S, respectively, although the former peak
      was broader, possibly reflecting the relative instability of the purified foetal
      receptor. Our finding of marked differences in the glycosylation of foetal and
      adult human acetylcholine receptors suggest that, in otherwise very similar
      proteins, the carbohydrate moieties could determine the known differences in
      location and stability of the two receptor types. 

PMID- 24874591
TI  - Vildagliptin compared to glimepiride on post-prandial lipemia and on insulin
      resistance in type 2 diabetic patients.
AB  - OBJECTIVES: To evaluate the effects of vildagliptin compared to glimepiride on
      glycemic control, insulin resistance and post-prandial lipemia. MATERIAL AND
      METHODS: 167 type 2 diabetic patients, not adequately controlled by metformin,
      were randomized to vildagliptin 50 mg twice a day or glimepiride 2 mg three times
      a day for 6 months, in a double blind, randomized clinical trial. We evaluated:
      body mass index (BMI), glycemic control, fasting plasma insulin (FPI),
      homeostasis model assessment insulin resistance index (HOMA-IR), fasting plasma
      proinsulin (FPPr), glucagon, lipid profile, resistin, retinol binding protein-4
      (RBP-4), visfatin and vaspin. Furthermore, at the randomization and at the end of
      the study all patients underwent an euglycemic hyperinsulinemic clamp to evaluate
      M value and an oral fat load. RESULTS: Despite a similar decrease of glycated
      hemoglobin, there were an increase of body weight with glimepiride + metformin
      and a decrease with vildagliptin + metformin. Fasting plasma insulin increased
      with glimepiride + metformin, while it did not change with vildagliptin +
      metformin. Vildagliptin + metformin improved lipid profile. Regarding insulin
      sensitivity, vildagliptin + metformin increased M value. Resistin, RBP-4, vaspin
      and visfatin were decreased by vildagliptin + metformin, but in group to group
      comparison, only vaspin reduction resulted statistically significant.
      Vildagliptin + metformin reduced post-prandial lipemia and insulinemia compared
      to glimepiride + metformin. CONCLUSION: Vildagliptin, in addition to metformin,
      was more effective than glimepiride + metformin in reducing insulin resistance
      and post-prandial lipemia.

PMID- 24874595
TI  - Neurogenesis in the olfactory tubercle and islands of Calleja in the rat.
AB  - Neurogenesis in the rat olfactory tubercle and islands of Calleja was examined
      with [(3)H]thymidine autoradiography. Animals in the prenatal groups were the
      offspring of pregnant females given an injection of [(3)H]thymidine on two
      consecutive gestational days. Ten groups of embryos (E) were exposed to
      [(3)H]thymidine on E12-E13, E13-E14 4 E21-E22, respectively. Three groups of
      postnatal animals (P) were given four consecutive injections of [(3)H]thymidine
      on P0-P3, P2-P5, and P4-P7, respectively. On P60, the percentage of labeled cells
      and the proportion of cells originating during either 24 or 48 h periods were
      quantified at several anatomical levels. Three populations of neurons were
      studied: 

PMID- 24874596
TI  - Delayed development of GFA immunoreactivity in the parietal cortex during thyroid
      hormone deficiency.
AB  - The influence of neonatal hypothyroidism on the development of immunoreactivity
      to glial fibrillary acidic protein (GFA) was studied in parietal cortex of rats
      treated from birth with the antithyroid agent propylthiouracil (PTU) for 3 or 8
      weeks. Density of GFA immunoreactivity was evaluated in cryostate sections
      reacted with an antiserum specific for GFA. Three weeks postnatally, the density
      of GFA-immunoreactive structures in the cortical layers II-V was 70% lower in PTU
      treated animals than in controls injected with the solvent. This marked
      difference between the groups was, however, not seen in either the molecular
      layer, layer VI or white matter. The inhibited development of GFA
      immunoreactivity was not persistent in animals treated with PTU for 8 weeks
      continuously. Plasma from animals treated with PTU for 1,2,3 and 8 weeks was
      collected and the TSH level in each group compared with samples from age-matched
      controls and newborn pups. The treatment with PTU resulted in a more than 10-fold
      increase in TSH level after 1 week of injections. In longterm groups of 8 weeks,
      the TSH level decreased in the PTU-treated animals, but stayed considerably
      higher than control values throughout the experiments. The results described in
      the present paper indicate a thyroid hormone dependent development of the GFA
      immunoreactivity in cortex cerebri astrocytes. 

PMID- 24874597
TI  - The ontogenesis of the dopaminergic cell in the pre- and postnatal guinea pig
      retina.
AB  - We have examined the development of the dopaminergic system of the guinea pig
      retina, a species in which retinal neuronal and synaptic differentiation occurs
      largely in utero. Fetal animals aged 42-69 days (full term), neonates, postnatal
      (pn) animals to 12 weeks, and mature animals were studied to determine retinal
      dopamine (DA) storage, metabolism (DOPAC), in vitro tyrosine hydroxylase (TH)
      activity, postsynaptic target activation (cAMP stimulation) and localization
      (formaldehyde-induced histofluorescence). DA-stimulated adenylate cyclase at 42
      days of gestation was threefold over basal activity, preceding the onset of the
      accumulation of DA and DOPAC at 45 days, and the initial localization of DA in
      cell perikarya at 47 days and in processes at 50 days. At birth DA and DOPAC
      levels were 45 and 37%, respectively, of adult levels. DA levels remained stable
      during the first few days pn, although in vitro TH activity was capable of
      stimulation by light in the neonate as in the mature animal. DA and TH activity
      increased from 1 week pn to reach adult levels by 10 weeks pn. Although a
      significant degree of development of the dopaminergic neurotransmitter system in
      the guinea pig occurs before birth the attainment of a fully mature system
      postnatally may require normal photic stimulation of physiologic activity. 

PMID- 24874598
TI  - Effects of sex steroids on the growth of neuronal processes in neonatal rat
      hypothalamus-preoptic area and cerebral cortex in primary culture.
AB  - Dissociated cells of neonatal rat hypothalamus-preoptic area and cerebral cortex
      were grown in primary culture, and the effects of sex steroids on neurons were
      morphometrically studied. In cultures of the hypothalamus-preoptic area estradiol
      17beta or testosterone propionate significantly increased the total neuronal
      process length as compared with control cultures given no steroids in the medium.
      Significant stimulatory effects were detected on 1, 2 and 3 days after plating,
      while, 5a-dihydrotestosterone failed to show any stimulatory influence. In
      contrast, none of these steroids was effective in cultures of cerebral cortical
      cells. Based on the number of processes arising from the soma, neurons were
      divided into unipolar, bipolar and multipolar neurons. Percentage of multipolar
      neurons of the hypothalamus-preoptic area was more in cultures treated with
      estradiol-17beta or testosterone propionate than the controls. Significant effect
      was not noted in cultures with 5alpha-dihydrotestosterone, while, in cultures of
      the cerebral cortical cells, effects on sprouting of these steroids were far less
      marked than in cultures of the hypothalamus-preoptic area. The present findings
      substantiate the importance of aromatization of androgen to exert its influence
      on neuronal process growth in cell culture. 

PMID- 24874599
TI  - Ontogenetic development of glutamate and GABA metabolizing enzymes in cultured
      cerebral cortex interneurons and in cerebral cortex in vivo.
AB  - The development of the enzymes phosphate activated glutaminase (PAG), glutamate
      dehydrogenase (GLDH), glutamic-oxaloacetic-transaminase (GOT), glutamine
      synthetase (GS), GABA-transaminase (GABA-T) and ornithine-delta-aminotransferase
      (Orn-T) was followed in mouse cerebral cortex in vivo and in cultured mouse
      cerebral cortex interneurons. It was found that GLDH, GOT and Orn-T exhibited an
      enhanced developmental pattern in the cultured neurons compared to cerebral
      cortex. The activities of PAG and GABA-T developed in parallel in vivo and in
      culture but the activity of GS remained low in the cultured neurons compared to
      the increasing activity of this enzyme found in vivo. Compared to cerebral cortex
      the cultured neurons exhibited higher activities of PAG, GLDH and Orn-T, whereas
      the activities of GABA-T and GOT were lower in the cultured cells. The activity
      of GS in the cultured neurons was only 5-10% of the activity in cerebral cortex
      in vivo. It is concluded that neurons from cerebral cortex represent a reliable
      model system by which the metabolism and function of GABAergic neurons can be
      conveniently studied in a physiologically meaningful way. 

PMID- 24874600
TI  - Ganglioside GM1 overcomes serum inhibition of neuritic outgrowth.
AB  - Considerable variations in both neuritic and non-neuronal cell outgrowths of
      ganglionic expiant cultures are imposed when different substrata and medium
      supplements are used. Therefore, a neuritic response to exogenous agents such as
      gangliosides may be better, or exclusively revealed under selected combinations
      of medium and substratum. We have surveyed a number of different ganglia for
      their ability to display a neuritic response to ganglioside GM1 and the culture
      conditions under which such a display may take place. GM1 can recognizably
      promote neurite extension from embryonic day 8 chick dorsal root ganglia, day 11
      sympathetic ganglia, and day 8 ciliary ganglia. Demonstration of such effects,
      however, requires an appropriate balance between promoting and inhibiting
      influences by other extrinsic influences (culture substrata, neuronotrophic
      factors, serum inhibitors) thereby allowing for improvement by the ganglioside.
      Different ganglia require different combinations of those influences. Ciliary
      ganglia, for example, will show a GM1 response on a polyornithine substratum in
      medium supplemented with the chick eye Ciliary Neuronotrophic Factor and 1% fetal
      calf serum, but not with 10% serum or no serum. The effective concentration range
      for GM1 is in accord with previously reported serum binding data. These, and
      other data are consistent with an action of GM1 in executing a neurite program,
      rather than an imposition of the program itself. 

PMID- 24874601
TI  - The expression of concanavalin a binding glycoproteins during the development of
      cerebellar granule neurons in vitro.
AB  - We present data on the expression of Concanavalin A (ConA) binding glycoproteins
      by granule cell enriched cultures derived from 8 day postnatal rat cerebellum.
      Time course studies were conducted over a 12 day culture period. ConA binding
      glycoproteins were localized on the cell bodies and fibres of the granule neurons
      using fluorescence microscopy. The fluorescence intensity increased between 4 and
      12 days in vitro. Quantitative studies on the capacity of live cells to bind
      (125)I-iodinated ConA showed that there was a significant increase in the amount
      of lectin bound between 4 and 8 days in vitro. However, in contrast to previous
      results on the developing cerebellum in vivo [Zanetta et al. (1978) Brain
      Res.142, 301-319.], there was no decline in binding capacity after 8 days in
      culture. Glycoproteins expressed by these cells were analysed by staining SDS
      polyacrylamide gels with [(125)I]ConA. A large number of lectin binding proteins
      were observed which spread over a wide range of molecular weights. Only minor
      changes were detected in the profile of [(125)I]ConA binding glycoproteins with
      the maturation of the cells in culture. The comparison of the findings on granule
      cells developing in culture and in vivo suggested that an interaction between
      granule cell axons and their normal target neurons is involved in the regulation
      of the ConA binding protein content in the cerebellum. 

PMID- 24874602
TI  - Dextran-coated gold nanoprobes for the concentration and detection of protein
      biomarkers.
AB  - The lateral-flow immunoassay (LFA) is a well-established point-of-care detection
      assay that is rapid, inexpensive, easy to use, and portable. However, its
      sensitivity is lower than that of traditional lab-based assays. Previously, we
      improved the sensitivity of LFA by concentrating the target biomolecules using
      aqueous two-phase systems (ATPSs) prior to their detection. In this study, we
      report the first-ever utilization of dextran-coated gold nanoprobes (DGNPs) as
      the colorimetric indicator for LFA. In addition, the DGNPs are the key component
      in our pre-concentration process, where they remain stable and functional in the
      high salt environment of our ATPS solution, capture the target protein with
      conjugated antibodies, and allow the rapid concentration of the target protein in
      our ATPS for use in the subsequent LFA detection step. By combining this pre
      concentration step with LFA, the detection limit of LFA for a model protein was
      improved by 10-fold. We further improved our ATPS from previous studies by
      enabling phase separation at room temperature in 30 min. By using DGNPs for the
      concentration and detection of protein biomarkers in the sequential combination
      of the ATPS and LFA steps, we move closer to developing an effective protein
      detection assay which uses no power or lab-based equipment. 

PMID- 24874603
TI  - Effects of antibiotic physicochemical properties on their release kinetics from
      biodegradable polymer microparticles.
AB  - PURPOSE: This study investigated the effects of the physicochemical properties of
      antibiotics on the morphology, loading efficiency, size, release kinetics, and
      antibiotic efficacy of loaded poly(DL-lactic-co-glycolic acid) (PLGA)
      microparticles (MPs) at different loading percentages. METHODS: Cefazolin,
      ciprofloxacin, clindamycin, colistin, doxycycline, and vancomycin were loaded at
      10 and 20 wt% into PLGA MPs using a water-in-oil-in water double emulsion
      fabrication protocol. Microparticle morphology, size, loading efficiency, release
      kinetics, and antibiotic efficacy were assessed. RESULTS: The results from this
      study demonstrate that the chemical nature of loaded antibiotics, especially
      charge and molecular weight, influence the incorporation into and release of
      antibiotics from PLGA MPs. Drugs with molecular weights less than 600 Da
      displayed biphasic release while those with molecular weights greater than 1,000
      Da displayed triphasic release kinetics. Large molecular weight drugs also had a
      longer delay before release than smaller molecular weight drugs. The negatively
      charged antibiotic cefazolin had lower loading efficiency than positively charged
      antibiotics. Microparticle size appeared to be mainly controlled by fabrication
      parameters, and partition and solubility coefficients did not appear to have an
      obvious effect on loading efficiency or release. Released antibiotics maintained
      their efficacy against susceptible strains over the duration of release. Duration
      of release varied between 17 and 49 days based on the type of antibiotic loaded.
      CONCLUSIONS: The data from this study indicate that the chemical nature of
      antibiotics affects properties of antibiotic-loaded PLGA MPs and allows for
      general prediction of loading and release kinetics.

PMID- 24874605
TI  - Rhodium-catalyzed enantioselective addition of organoaluminum reagents to N-tosyl
      ketimines.
AB  - Rhodium(I)/Binap complexes catalyze highly enantioselective additions of methyl-
      and arylaluminum reagents to cyclic alpha,beta-unsaturated N-tosyl ketimines.
      Depending on the solvent and substituents at the ring, the reaction occurs either
      in a 1,2-manner to deliver alpha-tertiary allylic amines or in a 1,4-manner to
      yield, after subsequent reduction, 3-substituted cycloalkyl amines. Well known in
      the case of the respective cycloalkenones, these first transformations of the aza
      analogues enable the synthesis of amine structures of pharmaceutical and
      biochemical interest. 

PMID- 24874604
TI  - Phosphorylation of serine 106 in Asef2 regulates cell migration and adhesion
      turnover.
AB  - Asef2, a 652-amino acid protein, is a guanine nucleotide exchange factor (GEF)
      that regulates cell migration and other processes via activation of Rho family
      GTPases, including Rac. Binding of the tumor suppressor adenomatous polyposis
      coli (APC) to Asef2 is known to induce its GEF activity; however, little is
      currently known about other modes of Asef2 regulation. Here, we investigated the
      role of phosphorylation in regulating Asef2 activity and function. Using high
      resolution mass spectrometry (MS) and tandem mass spectrometry (MS/MS), we
      obtained complete coverage of all phosphorylatable residues and identified six
      phosphorylation sites. One of these, serine 106 (S106), was particularly
      intriguing as a potential regulator of Asef2 activity because of its location
      within the APC-binding domain. Interestingly, mutation of this serine to alanine
      (S106A), a non-phosphorylatable analogue, greatly diminished the ability of Asef2
      to activate Rac, while a phosphomimetic mutation (serine to aspartic acid, S106D)
      enhanced Rac activation. Furthermore, expression of these mutants in HT1080 cells
      demonstrated that phosphorylation of S106 is critical for Asef2-promoted
      migration and for cell-matrix adhesion assembly and disassembly (adhesion
      turnover), which is a process that facilitates efficient migration. Collectively,
      our results show that phosphorylation of S106 modulates Asef2 GEF activity and
      Asef2-mediated cell migration and adhesion turnover. 

PMID- 24874606
TI  - Adult idiopatic occlusion of Monro foramina: intraoperative endoscopic
      reinterpretation of radiological data and review of the literature.
AB  - Adult idiopathic occlusion of the foramen of Monro (AIOFM) is a rare condition,
      with only few cases described in the modern literature. We propose that AIOFM may
      result from unilateral or bilateral occlusion of Monro foramina, as well as from
      progression of a monolateral hydrocephalus. Different surgical strategies may be
      required for effective treatment according to the type of occlusion. To date,
      only 12 cases of AIOFM have been reported in the literature. We report the cases
      of two patients, aged 20 and 47 years respectively, who presented with
      intracranial hypertension secondary to bilateral ventricular dilatation due to
      obstruction at the level of the foramen of Monro. Both patients were successfully
      treated with endoscopic fenestration of the primarily obstructed foramen of Monro
      and, in one patient, fenestration of the septum. We propose that septum
      pellucidum displacement could play a role in the occlusion of the second foramen
      of Monro. AIOFM can, therefore, result also from unilateral stenosis of Monro.
      The difference in AIOFM (i.e. unilateral vs bilateral) will be useful in guiding
      the most suitable surgical approach in this rare condition.

PMID- 24874607
TI  - Antibiotic de-escalation in bacteremic urinary tract infections: potential
      opportunities and effect on outcome.
AB  - PURPOSE: The aim of this study was to examine the safety and efficacy of
      antibiotic de-escalation in patients admitted with bacteremic urinary tract
      infection (UTI). METHODS: A retrospective chart review of patients admitted to a
      community-hospital in West Texas with bacteremic UTI during the year 2008.
      Antibiotic de-escalation was defined as changing the intravenous empiric
      antibiotic regimen to a culture-directed single agent, given intravenously or
      orally, with a narrower spectrum than the original empiric regimen. RESULTS:
      Ninety-seven patients were admitted with bacteremic UTI. Thirty-two patients were
      not eligible for de-escalation. Among the 65 patients who were eligible for de
      escalation, the treating physicians failed to de-escalate antibiotics in 31 cases
      (47.7%). Fluoroquinolones' resistance, bacteria other than Escherichia coli and
      discharge to long-term care facilities predicted failure to de-escalate
      antibiotics. On multivariate analysis, discharge to long-term care facility was
      the only risk factor that predicted failure to de-escalate antibiotics. The
      difference between mean hospital length of stay and mortality between the above
      two groups was not statistically significant. CONCLUSION: Antibiotic de
      escalation is under-recognized and sporadically practiced. In patients admitted
      with bacteremic UTI, empiric antibiotic regimen can be changed to a culture
      directed single antibiotic without an increase in hospital length of stay or
      patients' mortality.

PMID- 24874609
TI  - Heartfelt imitation: high interoceptive awareness is linked to greater automatic
      imitation.
AB  - 'Interoceptive awareness', defined as the individual's awareness of internal body
      signals, modulates self/other distinction under conditions of multisensory
      integration. We examined here, for the first time, the potential impact of
      interoceptive awareness on self/other distinction in the motor domain. In
      automatic imitation, inhibition of imitation is an index of an individual's
      success in distinguishing internally generated motor representations from those
      triggered by observing another person's action. This is measured by the
      'congruency effect', which is the difference between mean reaction times when the
      observed action is 'incongruent' with the required action and when it is
      'congruent'. The present study compared the congruency effect in a typical finger
      lifting paradigm, with interoceptive awareness measured by heartbeat perception.
      Contrary to expectation, interoceptive awareness was positively correlated with
      the congruency effect and this effect depended on mean reaction times in the
      incongruent condition, indicating that good heartbeat perceivers had more
      difficulty inhibiting the tendency to imitate. Potentially, high interoceptive
      awareness involves stronger interoceptive representations of the consequences of
      an action, implying higher empathy, greater motor reactivity in response to
      observed action and hence a greater tendency to imitate. Our results may also
      tentatively be explained within a predictive coding account of interoception. 

PMID- 24874608
TI  - AMPK couples p73 with p53 in cell fate decision.
AB  - The p53 family of proteins has an important role in determining cell fate in
      response to different types of stress, such as DNA damage, hypoxia, or oncogenic
      stress. In recent years, p53 has also been shown to respond to metabolic stress,
      and to be induced by the AMP-activated protein kinase (AMPK), a central cellular
      energy sensor. A bioinformatic analysis revealed three putative AMPK
      phopshorylation sites in p73, a p53 tumor suppressor paralog. In vitro and in
      vivo assays confirmed that AMPK phosphorylates p73 on a novel residue, S426.
      Following specific pharmacologic stimulation of AMPK in cells, p73 protein half
      life was prolonged leading to p73 accumulation in the nucleus. We show that p73
      escaped the E3 ligase Itch resulting in reduced p73 ubiquitination and
      proteasomal degradation. Furthermore, chronic activation of AMPK led to apoptosis
      that was p73 dependent, but only in p53-expressing cells. Surprisingly, we found
      that p73 was required for p53 stabilization and accumulation under AMPK
      activation, but was dispensable under DNA damage. Our findings couple p73 with
      p53 in determining cell fate under AMPK-induced metabolic stress. 

PMID- 24874610
TI  - Effect of a Pulmonary Rehabilitation Program on the levels of anxiety and
      depression and on the quality of life of patients with chronic obstructive
      pulmonary disease.
AB  - OBJECTIVE: To analyze the effect of a Pulmonary Rehabilitation Program (PRP) on
      the levels of anxiety and depression and the quality of life of patients with
      chronic obstructive pulmonary disease. METHOD: Patients with chronic obstructive
      pulmonary disease (COPD) who completed the PRP of 3 weekly sessions of 60 min
      duration for 12 weeks, a total of 36 sessions, were assessed using Beck Inventory
      (BAI and BDI) and Saint George's Respiratory Questionnaire (SGRQ). RESULTS: A
      total of 125 individuals, with an average age of 63.7 +/- 8.8 years, FEV1: 1.17
      +/- 0.57L (43.18 +/- 18.79% predicted), 61.6% male and 38.4% female, were
      analyzed. The BAI and BDI before and after PRP were, respectively, 10.15 +/- 6.32
      vs. 7.67 +/- 7.21; p=0.0041 and 12.60 +/- 7.99 vs. 8.96 +/- 7.29; p=0.00016. The
      results of the SGRQ domains were, respectively, Before and After symptoms (48.53
      +/- 20.41 vs. 32.58 +/- 18.95), Activity (69.15 +/- 20.79 vs. 52.42 +/- 23.70),
      Impact (32.92 +/- 18.29 vs. 20.27 +/- 16.70), Total (46.69 +/- 16.90 vs. 32.07 +/
      16.96). When correlating the BDI to the domains of the SGRQ, weak correlations
      were observed (Symptoms r=0.22; p=0.01; Activity r=0.28; p=0.001; Impact r=0.52;
      p=2.72; Total r=0.44; p=0.17). In the same way, weak correlations were observed
      when correlating the BAI to the SGRQ (Symptoms r=0.28; p=0.0009; Activity r=0.32;
      p=0.0005; Impact r=0.42; p=7.33; Total r=0.43; p=0.74). CONCLUSION: Although the
      PRP improves levels of depression and anxiety as well as the quality of life in
      patients with COPD, no significant correlation of these analyzed variables was
      observed.

PMID- 24874611
TI  - Invited commentary to "adjuvant chemotherapy increases the prevalence of fat
      necrosis in immediate free abdominal flap breast reconstruction" by Wu J, Lin L,
      Chen Y, Chen J, Yang B, Li J, Huang X, Shen Z, Shao Z, Yu P.

PMID- 24874612
TI  - Melkersson-Rosenthal syndrome: a facial nerve center perspective.
AB  - OBJECTIVES: Melkersson-Rosenthal syndrome (MRS) is a rare neuro-mucocutaneous
      granulomatous disorder of unknown etiology, characterized by the triad of facial
      palsy, lingua plicata (fissured tongue), and orofacial edema. Few articles in the
      literature report series with more than 20 patients or focus on the facial nerve
      dominant presentation of MRS. METHODS: We performed a retrospective review of the
      patients diagnosed with MRS at a university-based Facial Nerve Center. RESULTS:
      Twenty-one patients were identified from 1971 to 2010. The age of presentation
      ranged from 22 to 67 years (mean 44.1). Seven (33.3%) were male and 14 (66.7%)
      were female. All (100%) patients had facial paralysis. Fourteen (66.7%) patients
      who initially presented with unilateral paralysis subsequently developed
      metachronous contralateral paralysis (alternating unilateral facial paralysis).
      One (4.7%) patient had simultaneous bilateral facial paralysis. The number of
      episodes per patient ranged from 1 to 8 (mean 3.1). Laterality was relatively
      equal: 35 episodes occurred on the right side and 31 on the left. The patient
      with most episodes of facial paralysis had four on the left and four on the right
      (metachronous). This was followed by three patients with six episodes each. The
      age of first incidence of facial paralysis ranged from 2 to 60 years (mean 34.4,
      median of 39). The mean interval between episodes was 4.7 years (range 0-30,
      median 3). Six (28.5%) of the patients reported a family history of MRS.
      CONCLUSIONS: MRS is a rare disease of unknown pathogenesis in which
      oligosymptomatic forms predominate. Patients with this disease may present to
      different specialties complaining of different symptoms, and frequently, not all
      the classic features of the triad will be present. In our series of facial
      paralysis patients diagnosed with MRS, a higher proportion had the full triad of
      symptoms than has been previously reported in the literature.

PMID- 24874613
TI  - 21 year follow up of a DIEP (deep inferior epigastric perforator) flap: a tale of
      a "nulltiple".
AB  - Since the first description of "The free abdominoplasty flap for breast
      reconstruction" by Hans Holmstrom in 1979, [see Ref. 1] the use of lower
      abdominal tissue has revolutionised reconstruction of the breast. DIEP (deep
      inferior epigastric perforator) free flap offers an abundance of reconstructive
      material, aesthetically-pleasing results and limited donor site morbidity. We
      report our first case of breast reconstruction with what presently is known as
      DIEP flap, performed in 1991 at St. Andrew's Centre for Plastic Surgery and Burns
      in Essex, The United Kingdom and the recent follow up results. We also discuss
      the historical events surrounding the evolution of this unpublished case and
      other documented cases. 

PMID- 24874614
TI  - Staying strong.
AB  - Each June Age UK marks falls awareness week. The charity highlights that falls
      and fractures in people aged 65 and over are responsible for more than four
      million hospital bed days a year in England. They also have significant long-term
      effects such as loss of confidence, increased isolation and reduced independence.

PMID- 24874615
TI  - Government promises to train all NHS staff in dementia care by 2018.
AB  - ALL NHS staff will have received dementia training by 2018, according to a Health
      Education England mandate. 

PMID- 24874616
TI  - Updated guidance on pressure ulcer prevention issued.
AB  - PATIENTS 'AT risk' of developing pressure ulcers should be repositioned at least
      every six hours and those 'at high risk' should have their position changed at
      least every four hours, according to new guidance. 

PMID- 24874618
TI  - Petition may trigger parliamentary debate on regulator's fee.
AB  - THE NURSING and Midwifery Council's (NMC) proposed registration fee increase to
      L120 is likely to be debated in parliament after a petition against the rise
      reached 100,000 signatures. The petition, started by mental health liaison nurse
      Steve Iwasyk, gained the necessary number of signatures to spark a debate. 

PMID- 24874619
TI  - Tiger feet hit really is neat.
AB  - CLINICIANS WORKING with patients with Parkinson's disease have applied for
      funding to carry out research into the link between the condition and music. 

PMID- 24874620
TI  - Scheme aims to boost status of healthcare assistants.
AB  - THE VIEWS of patients could be sought on whether healthcare support workers are
      fit to work unsupervised as part of a care certificate being launched this
      summer. 

PMID- 24874621
TI  - Everyone is responsible for preventing further abuse.
AB  - A BBC Panorama documentary exposing poor quality care in nursing homes has
      prompted one of the company's portrayed to consider the use of CCTV to tackle
      abuse and neglect of residents. 

PMID- 24874622
TI  - Health hazards from loneliness put pressure on NHS and local services.
AB  - NURSES AND other front line health staff are being urged to be on the lookout for
      people who are lonely, following the publication of new figures that suggest
      numbers are on the rise. 

PMID- 24874623
TI  - Forum focus - taking part counts.
AB  - INCREASED PARTICIPATION of members is vital to the success of the Royal College
      of Nursing, which is why congress is such a pivotal event in the organisation's
      calendar. Two major changes at this month's congress aim to highlight the
      importance of member participation: the annual general meeting will be held and
      the forum steering committee elections launched. 

PMID- 24874624
TI  - Steps towards dementia-friendly communities applauded.
AB  - I agree with the need to provide dementia awareness training for healthcare
      professionals (Nursing Older People. 25, 8, 5). According to the World Health
      Organization, more than 35 million people worldwide have dementia, and with the
      ageing of the global population, this number will grow to more than 100 million
      by 2050. 

PMID- 24874630
TI  - True cost of care.
AB  - In The wake of the shocking abuse of frail and vulnerable care home residents
      featured in a recent BBC Panorama documentary, the call for solutions is
      understandable. But, sadly, there are no quick or cheap answers. More
      inspections, installation of surveillance cameras in residents' rooms and
      prosecution of abusers might assuage public anger for now, but they are as likely
      to end abuse as to find a cure for dementia.

PMID- 24874634
TI  - Practice question.
AB  - The Advocacy Network Northern Ireland describes advocacy as 'the act of speaking
      up for people who are not being heard and supporting them to express their own
      views and ultimately, where possible, to make their own decisions and take
      control over their lives' ( Patient and Client Council 2012 ). 

PMID- 24874635
TI  - Assessment and management of older people with sarcopenia.
AB  - Sarcopenia, the loss of skeletal muscle mass and function with age, is common in
      older people. It is associated with increased morbidity and mortality, and a
      greater risk of admission to hospital and care homes. This article identifies the
      risk factors and consequences of sarcopenia, and describes how nurses and GPs can
      recognise patients at particular risk of developing the condition. Evidence for
      the management of sarcopenia is discussed with regard to lifestyle and potential
      future therapeutic developments. 

PMID- 24874636
TI  - New responsibilities in purchasing and developing services.
AB  - The role of nursing in the NHS commissioning structure in England is developing.
      Since April 2013 more than 200 clinical commissioning groups (CCGs), which
      comprise all GP practices in the locality, have taken on responsibility for
      health budgets in their areas. This article describes the challenges ahead and
      nurses' responsibilities in CCGs when working with local citizens and across the
      health and social care system to assure the delivery of high quality, safe
      services. 

PMID- 24874637
TI  - The effect of dementia on patients, informal carers and nurses.
AB  - This article explores the effect of dementia on individuals with dementia, their
      families and nursing staff. It explores the diagnostic issues that are important
      for individuals, the effect of symptoms and avenues of support. The need to adapt
      to different roles and the importance of communication are discussed for families
      and informal carers. Lastly, the culture of nursing care and the need for
      education, training, professional development and clinical supervision is
      discussed. The literature emphasises the need for close collaborative working
      between those involved in dementia care, with individuals with dementia at the
      centre of decision making. It highlights how everyone involved can contribute to
      positive care experiences for those with the condition. 

PMID- 24874638
TI  - An overview of communication, movement and perception difficulties after stroke.
AB  - For many people who have had a stroke, weakness or paralysis on one side -
      hemiparesis or hemiplegia - is the most obvious symptom. However, brain damage,
      including stroke, can cause a range of impairments that may be less obvious but
      equally devastating for people and their families. This article provides an
      overview of communication, movement and perception difficulties, and the
      strategies nurses can use to help people cope with any changes to their lives. 

PMID- 24874639
TI  - A real 'people person'.
AB  - TOWARDS THE end of Sharon Blackburn's schooldays she undertook a two-day work
      placement at a local hospital in north London. At the end of the two days, she
      was summoned for feedback. 'They thought I was a real people person,' she says.
      'They thought nursing would fit me and I would fit it.' 

PMID- 24874641
TI  - Registration of clinical trials for publication.

PMID- 24874642
TI  - Kinematic impact of size on the existing glenohumeral joint in patients
      undergoing reverse shoulder arthroplasty.
AB  - BACKGROUND: Glenohumeral relationships in reverse shoulder arthroplasty patients
      have not been previously reported. The purpose of this study was to quantify and
      compare the shoulder spatial relationships and moment arms. Measurements were
      used to define general size categories and determine if sizes scale linearly for
      all metrics. METHODS: Ninety-two shoulders of patients undergoing primary reverse
      shoulder arthroplasty for functionally-deficient massive rotator cuff tear
      without bony deformity or deficiency were evaluated using three-dimensional CT
      reconstructions and computer-aided design software. Multiple glenohumeral
      relationships (including moment arm) were measured and evaluated for size
      stratification and linearity. Generalized linear modeling was used to investigate
      how predictive glenoid height, coronal humeral head diameter, and gender were of
      greater tuberosity positions. FINDINGS: The 92 shoulders were grouped based on
      glenoid height: small (<33.4mm), medium (33.4-38.0mm), and large (>38.0mm). All
      relationships varied between groups. The humeral head size, glenoid width,
      lateral offset, and moment arm all independently increased linearly (r(2)>=0.92)
      but the rate of increase varied (slope range: 0.59-1.92). Glenoid height, coronal
      humeral head diameter and gender predicted the greater tuberosity position within
      mean 1.09mm (standard deviation (SD) 0.84mm) of actual position in 90% of the
      population. INTERPRETATION: Distinct groups exist based on the size of the
      glenoid in shoulder arthroplasty patients. Shoulder modeling should account for
      size groups, sex, and non-uniform linear scaling of morphometric parameters.
      Prediction of the greater tuberosity offset can be made using sex and size
      parameters. Clinical implications include appropriate prosthetic size selection
      and avoiding large deviations in non-anatomic reconstructions.

PMID- 24874643
TI  - The good pain management (GPM) ward program in China and its impact on Chinese
      cancer patients: the SYSUCC experience.
AB  - To improve cancer pain management, the Medical Oncology Department of Sun Yat-sen
      University Cancer Center (SYSUCC) launched the Good Pain Management (GPM) Ward
      Program, which has been recognized by the Chinese Ministry of Health and promoted
      throughout the nation. This retrospective case-control study was designed to
      evaluate the effectiveness of the program. Patients diagnosed with malignant
      solid tumors with bone metastasis were eligible. Patients who were admitted 6
      months before the initiation of the GPM program were used as the control group,
      and patients admitted 6 months after the initiation of the program were used as
      the GPM group. The pain-reporting rate and pain management index (PMI) were
      calculated. The pain levels before and after pain management were compared. A
      total of 475 patients (244 in the control group and 231 in the GPM group) were
      analyzed. The pain-reporting rate of the GPM group was significantly higher than
      that of the control group (62.8% vs. 37.7%, P < 0.001). The PMI of the GPM group
      was significantly higher than that of the control group (0.083 vs. -0.261, P <
      0.001). Therefore, the GPM Ward Program improved the pain management of cancer
      patients and provided experience for improving cancer pain management in the
      future. 

PMID- 24874645
TI  - Hepcidin quantification: methods and utility in diagnosis.
AB  - Hepcidin is a 25-amino acid peptide hormone that is produced and secreted
      predominantly by hepatocytes, circulates in the bloodstream, and is excreted by
      the kidneys. Since the discovery of hepcidin and the elucidation of its important
      role in iron homeostasis, hepcidin has been suggested as a promising diagnostic
      marker for iron-related disorders. In this regard, a number of analytical methods
      have been developed in order to assess hepcidin concentration in different
      biological fluids, particularly serum and urine. In this critical review we have
      tried to address the issues still pending in accurate determination of this
      peptide by evaluating the available analytical methodologies. Among them, the use
      of ELISA strategies (in competitive or sandwich formats) and molecular mass
      spectrometry (MS) including MALDI and/or LC-MS has been critically compared. The
      use of elemental mass spectrometry (ICP-MS) has also been included as a possible
      complementary tool to the previous ones. In addition, this manuscript has revised
      the existing and potentially emerging clinical applications of hepcidin testing
      for diagnosis. These include the iron disorders such as iron deficiency anemia
      (IDA, low hepcidin), anemia of chronic disease (ACD, high hepcidin) and the
      combined state of ACD and IDA or hemochromatosis. Other applications such as
      using hepcidin in assessing the response to existing therapies in cancer have
      also been revised in the manuscript. 

PMID- 24874644
TI  - Plasma microRNA profiling in nasopharyngeal carcinoma patients reveals miR-548q
      and miR-483-5p as potential biomarkers.
AB  - MicroRNAs (miRNAs), which play a role in tumorigenesis, may also serve as
      diagnostic or prognostic biomarkers. However, studies on human miRNA profiles in
      plasma from nasopharyngeal carcinoma (NPC) patients are in their infancy. Here,
      we used microarrays to perform systematic profiling of human miRNAs in plasma
      from NPC patients. We subsequently used real-time quantitative polymerase chain
      reaction (Q-PCR) to validate miRNAs with aberrant expression that could serve as
      potential biomarkers. By comparing the plasma miRNA profiles of 31 NPC patients
      and 19 controls, 39 of 887 human miRNAs were found to be aberrantly expressed.
      Considering the fold change and P value, miR-548q and miR-483-5p were validated
      in 132 samples from 82 NPC patients and 50 controls. Moreover, high expression of
      miR-548q and miR-483-5p was further found in 3 NPC cell lines and clinical biopsy
      tissues from 54 NPC patients and 22 controls. Our results revealed that miR-548q
      and miR-483-5p are potential biomarkers of NPC. Combining the receiver operating
      characteristic (ROC) analyses of these 2 miRNAs, an area under the ROC curve
      (AUC) of 0.737 with 67.1% sensitivity and 68.0% specificity were obtained,
      showing the preliminary diagnostic value of plasma miRNAs. Moreover, most NPC
      patients with a poor outcome exhibited high expression (> median) of miR-548q
      (70.6%) and miR-483-5p (64.7%) in tissue samples, indicating their prognostic
      value. The high expression levels of miR-548q and miR-483-5p in plasma, cell
      lines, and clinical tissues of NPC patients indicate that their roles in NPC
      should be explored in the future. 

PMID- 24874646
TI  - Exploring the potential of flubendazole in filariasis control: evaluation of the
      systemic exposure for different pharmaceutical preparations.
AB  - The goal of elimination of the human filariases would benefit greatly from the
      use of a macrofilaricidal agent. In vivo trials in humans and many experimental
      animal models suggest that flubendazole (FLBZ) is a highly efficacious
      macrofilaricide. However, since serious injection site reactions were reported in
      humans after parenteral FLBZ administration, the search for alternative
      pharmaceutical strategies to improve the systemic availability of FLBZ and its
      metabolites has acquired urgency in both human and veterinary medicine. The goal
      of the current work was to compare the systemic exposure of FLBZ formulated as
      either an aqueous hydroxypropyl-beta-cyclodextrin (CD) or aqueous carboxymethyl
      cellulose (CMC) suspension or a Tween 80-based formulation (TWEEN) in rats and
      jirds (Meriones unguiculatus). Healthy animals of both species were allocated
      into four experimental groups of 44 animals each: FLBZ-CD oral and FLBZ-CDsc,
      treated with the FLBZ-CD formulation by the oral or subcutaneous routes,
      respectively; FLBZ-TWEENsc, dosed subcutaneously with the FLBZ-TWEEN formulation;
      and FLBZ-CMC oral, treated orally with the FLBZ suspension. The FLBZ dose was 5
      mg/kg. FLBZ and its hydrolyzed (H-FLBZ) and reduced (R-FLBZ) metabolites were
      recovered in plasma samples collected from rats and jirds treated with the
      different FLBZ formulations. In both species, FLBZ parent drug was the main
      analyte recovered in the bloodstream. In rats, FLBZ systemic exposure (AUC 0-LOQ)
      was significantly (P < 0.05) higher after the FLBZ-CD treatments, both oral (4.8
      +/- 0.9 ug.h/mL) and subcutaneous (7.3 +/- 0.6 ug.h/mL), compared to that
      observed after oral administration of FLBZ-CMC suspension (0.93 +/- 0.2 ug.h/mL).
      The same differences were observed in jirds. In both species, parenteral
      administration of FLBZ-TWEEN did not improve the systemic availability of FLBZ
      compared to FLBZ-CDoral treatment. In conclusion, formulation approaches that
      enhance the availability of flubendazole in the rat and jird may have therapeutic
      implications for a drug with poor or erratic bioavailability.

PMID- 24874648
TI  - Roles of fatty acid ethanolamides (FAE) in traumatic and ischemic brain injury.
AB  - Ethanolamides of long-chain fatty acids are a class of endogenous lipid mediators
      generally referred to as N-acylethanolamines (NAEs). NAEs include anti
      inflammatory and analgesic palmitoylethanolamide, anorexic oleoylethanolamide,
      stearoylethanolamide, and the endocannabinoid anandamide. Traumatic brain injury
      (TBI), associated with a high morbidity and mortality and no specific therapeutic
      treatment, has become a pressing public health and medical problem. TBI is a
      complex process evoking systemic immune responses as well as direct local
      responses in the brain tissues. The direct (primary) damage disrupts the blood
      brain barrier (BBB), injures the neurons and initiates a cascade of inflammatory
      reactions including chemokine production and activation of resident immune cells.
      The effect of TBI is not restricted to the brain; it can cause multi-organ damage
      and evoke systemic immune response with cytokine and chemokine production. This
      facilitates the recruitment of immune cells to the site of injury and progression
      of the inflammatory reaction. Depending on severity, TBI induces immediate
      neuropathologic effects that, for the mildest form, may be transient; however,
      with increasing severity, these injuries cause cumulative neural damage and
      degeneration. Moreover, TBI leads to increased catabolism of phospholipids,
      resulting in a series of phospholipid breakdown products, some of which have
      potent biological activity. Ischemia-reperfusion (I/R) injury resulting from
      stroke leads to metabolic distress, oxidative stress and neuroinflammation,
      making it likely that multiple therapeutic intervention strategies may be needed
      for successful treatment. Current therapeutic strategies for stroke need
      complimentary neuroprotective treatments to provide a better outcome. Prior
      studies on NAEs have demonstrated neurotrophic/neuroprotective activities across
      a broad spectrum of cellular and animal models of neurodegenerative and acute
      cerebrovascular disorders. The present review will summarize our knowledge of the
      biological role of these lipid signaling molecules in brain and highlights their
      therapeutic effect from multipotential actions on neuronal cell death and
      neuroinflammatory pathways. 

PMID- 24874647
TI  - Antileishmanial activity of a series of N2,N4-disubstituted quinazoline-2,4
      diamines.
AB  - A series of N(2),N(4)-disubstituted quinazoline-2,4-diamines has been synthesized
      and tested against Leishmania donovani and L. amazonensis intracellular
      amastigotes. A structure-activity and structure-property relationship study was
      conducted in part using the Topliss operational scheme to identify new lead
      compounds. This study led to the identification of quinazolines with EC50 values
      in the single digit micromolar or high nanomolar range in addition to favorable
      physicochemical properties. Quinazoline 23 also displayed efficacy in a murine
      model of visceral leishmaniasis, reducing liver parasitemia by 37% when given by
      the intraperitoneal route at 15 mg kg(-1) day(-1) for 5 consecutive days. Their
      antileishmanial efficacy, ease of synthesis, and favorable physicochemical
      properties make the N(2),N(4)-disubstituted quinazoline-2,4-diamine compound
      series a suitable platform for future development of antileishmanial agents. 

PMID- 24874650
TI  - Buick Lucerne drivers' experiences with rear parking sensors.
AB  - OBJECTIVE: Rear parking sensors may have the potential to reduce property damage
      caused by some low-speed backing crashes, but their effectiveness depends on
      drivers' acceptance and proper use. This study examined owners' experiences with
      Buick Lucerne models with a rear parking sensor system. METHODS: Mail surveys
      were conducted in May 2013 with 426 owners of model year 2010-11 Buick Lucerne
      sedans equipped with the optional Ultrasonic Rear Parking Assist feature.
      RESULTS: Respondents were primarily older drivers, with 95% older than 60 and 70%
      older than 70. Nearly all owners reported that they always leave the system on,
      do not find it distracting, and would want it on their next vehicle. Slightly
      more than half (56%) said they had heard an alert and noticed something behind
      their vehicle they did not expect, which most commonly was a person or animal.
      Owners who said their behavior had changed while using the system mostly reported
      positive changes (e.g., increased alertness or confidence). In addition to an
      audible alert, systems on 2010 models provide information on the distance to rear
      objects via lights located near the rear windshield; 26% of owners with these
      systems reported never seeing the lights illuminate while backing up, and the
      percentage increased with age. CONCLUSIONS: Acceptance of the system was high,
      which is consistent with prior research on early adopters of rear parking
      sensors. Few owners reported problems using the system, and most problems were
      likely not attributed to age-related impairments, with the exception of those who
      did not see the 2010 model's warning lights. Use and acceptance of collision
      avoidance technologies should continue to be assessed among drivers of all ages
      as the systems become more widely available.

PMID- 24874651
TI  - A novel silk-based artificial ligament and tricalcium phosphate/polyether ether
      ketone anchor for anterior cruciate ligament reconstruction - safety and efficacy
      in a porcine model.
AB  - Loss of ligament graft tension in early postoperative stages following anterior
      cruciate ligament (ACL) reconstruction can come from a variety of factors, with
      slow graft integration to bone being widely viewed as a chief culprit. Toward an
      off-the-shelf ACL graft that can rapidly integrate to host tissue, we have
      developed a silk-based ACL graft combined with a tricalcium phosphate
      (TCP)/polyether ether ketone anchor. In the present study we tested the safety
      and efficacy of this concept in a porcine model, with postoperative assessments
      at 3months (n=10) and 6months (n=4). Biomechanical tests were performed after
      euthanization, with ultimate tensile strengths at 3months of ~370N and at 6months
      of ~566N - comparable to autograft and allograft performance in this animal
      model. Comprehensive histological observations revealed that TCP substantially
      enhanced silk graft to bone attachment. Interdigitation of soft and hard tissues
      was observed, with regenerated fibrocartilage characterizing a transitional zone
      from silk graft to bone that was similar to native ligament bone attachments. We
      conclude that both initial stability and robust long-term biological attachment
      were consistently achieved using the tested construct, supporting a large
      potential for silk-TCP combinations in the repair of the torn ACL. 

PMID- 24874652
TI  - Cotton-wool-like bioactive glasses for bone regeneration.
AB  - Inorganic sol-gel solutions were electrospun to produce the first bioactive three
      dimensional (3-D) scaffolds for bone tissue regeneration with a structure like
      cotton-wool (or cotton candy). This flexible 3-D fibrous structure is ideal for
      packing into complex defects. It also has large inter-fiber spaces to promote
      vascularization, penetration of cells and transport of nutrients throughout the
      scaffold. The 3-D fibrous structure was obtained by electrospinning, where the
      applied electric field and the instabilities exert tremendous force on the
      spinning jet, which is required to be viscoelastic to prevent jet break up.
      Previously, polymer binding agents were used with inorganic solutions to produce
      electrospun composite two-dimensional fibermats, requiring calcination to remove
      the polymer. This study presents novel reaction and processing conditions for
      producing a viscoelastic inorganic sol-gel solution that results in fibers by the
      entanglement of the intermolecularly overlapped nanosilica species in the
      solution, eliminating the need for a binder. Three-dimensional cotton-wool-like
      structures were only produced when solutions containing calcium nitrate were
      used, suggesting that the charge of the Ca(2+) ions had a significant effect. The
      resulting bioactive silica fibers had a narrow diameter range of 0.5-2MUm and
      were nanoporous. A hydroxycarbonate apatite layer was formed on the fibers within
      the first 12h of soaking in simulated body fluid. MC3T3-E1 preosteoblast cells
      cultured on the fibers showed no adverse cytotoxic effect and they were observed
      to attach to and spread in the material. 

PMID- 24874653
TI  - 2-Substituted 3-methylnaphtho[1,2-b]furan-4,5-diones as novel L-shaped ortho
      quinone substrates for NAD(P)H:quinone oxidoreductase (NQO1).
AB  - A series of L-shaped ortho-quinone analogs were designed by analyzing the binding
      mode with NQO1. Metabolic studies demonstrated that compounds 2m, 2n and 2q
      exhibited higher metabolic rates than beta-lapachone. The docking studies, which
      supported the rationalization of the metabolic studies, constituted a prospective
      rational basis for the development of optimized ortho-quinone analogs. Besides,
      good substrates (2m, 2n and 2r) for NQO1 showed higher selective toxicity than
      beta-lapachone toward A549 (NQO1-rich) cancer cells versus H596 (NQO1-deficient)
      cells. Determination of superoxide (O2(*-)) production and in vitro cytotoxicity
      evaluation in the presence of the NQO1 inhibitor dicoumarol confirmed that the
      ortho-quinones exerted their antitumor activity through NQO1-mediated ROS
      production by redox cycling. It was suggested that the L-shaped quinone
      substrates for NQO1 possessed better specificity and safety than beta-lapachone.

PMID- 24874655
TI  - in vivo ischemia monitoring array for endoscopic surgery.
AB  - An array with all-solid-state, potentiometric, miniaturized sensors for pH and
      potassium was developed to be introduced into the stomach or other sectors of the
      digestive tract by means of flexible endoscopy. These sensors perform continuous
      and simultaneous measurement of extracellular pH and potassium. This detection
      seeks to sense ischemia in the gastric mucosa inside the stomach, an event
      indicative of local microvascular perfusion and tissue oxygenation status. Our
      array is proposed as a medical tool to identify the occurrence of the ischemia
      after gastrointestinal or gastroesophageal anastomosis. The stability and
      feasibility of the miniaturized working and reference electrodes integrated in
      the array were studied under in vitro conditions, and the behavior of the
      potassium and pH ion-selective membranes were optimized to work under acidic
      gastric conditions with high concentrations of HCl. The array was tested in vivo
      in pigs to measure the ischemia produced by clamping the blood flow into the
      stomach. Our results indicate that ischemic and reperfusion states can be sensed
      in vivo and that information on tissue damage can be collected by this sensor
      array. The device described here provides a miniaturized, inexpensive, and mass
      producible sensor array for detecting local ischemia caused by unfavorable
      anastomotic perfusion and will thus contribute to preventing anastomotic leakage
      and failure caused by tissue necrosis. 

PMID- 24874654
TI  - The cytoplasmic domain of varicella-zoster virus glycoprotein H regulates
      syncytia formation and skin pathogenesis.
AB  - The conserved herpesvirus fusion complex consists of glycoproteins gB, gH, and gL
      which is critical for virion envelope fusion with the cell membrane during entry.
      For Varicella Zoster Virus (VZV), the complex is necessary for cell-cell fusion
      and presumed to mediate entry. VZV causes syncytia formation via cell-cell fusion
      in skin and in sensory ganglia during VZV reactivation, leading to neuronal
      damage, a potential contributory factor for the debilitating condition of
      postherpetic neuralgia. The gH cytoplasmic domain (gHcyt) is linked to the
      regulation of gB/gH-gL-mediated cell fusion as demonstrated by increased cell
      fusion in vitro by an eight amino acid (aa834-841) truncation of the gHcyt. The
      gHcyt regulation was identified to be dependent on the physical presence of the
      domain, and not of specific motifs or biochemical properties as substitution of
      aa834-841 with V5, cMyc, and hydrophobic or hydrophilic sequences did not affect
      fusion. The importance of the gHcyt length was corroborated by stepwise deletions
      of aa834-841 causing incremental increases in cell fusion, independent of gH
      surface expression and endocytosis. Consistent with the fusion assay, truncating
      the gHcyt in the viral genome caused exaggerated syncytia formation and
      significant reduction in viral titers. Importantly, infection of human skin
      xenografts in SCID mice was severely impaired by the truncation while maintaining
      the gHcyt length with the V5 substitution preserved typical replication in vitro
      and in skin. A role for the gHcyt in modulating the functions of the gB
      cytoplasmic domain (gBcyt) is proposed as the gHcyt truncation substantially
      enhanced cell fusion in the presence of the gB[Y881F] mutation. The significant
      reduction in skin infection caused by hyperfusogenic mutations in either the
      gHcyt or gBcyt demonstrates that both domains are critical for regulating
      syncytia formation and failure to control cell fusion, rather than enhancing
      viral spread, is severely detrimental to VZV pathogenesis. 

PMID- 24874656
TI  - Electrochemical methods for detection of post-translational modifications of
      proteins.
AB  - Post-translational modifications of proteins play a key role in the regulation of
      various cellular processes. The analysis and identification of post-translational
      modifications are probably the most versatile and difficult, but also most
      frequently studied area of interest in proteomics research. This review focuses
      on the electroactivity of amino acids as a tool for analysis of post
      translational modifications of proteins. The most attention is paid to the
      electrochemical detection of phosphorylation/dephosphorylation and glycosylation
      of proteins, to the best-studied and functionally-significant modifications, and,
      also, to the electrochemical analysis of activity of enzymes responsible for
      carrying out phosphorylation/dephosphorylation of proteins. Recent advances in
      electrochemistry with special references to proteomics are outlined and
      innovative technologies for protein detection are highlighted. 

PMID- 24874657
TI  - Nanovesicle-based platform for the electrophysiological monitoring of aquaporin-4
      and the real-time detection of its antibody.
AB  - Aquaporin-4 (AQP4) water channel protein transports water molecules across cell
      membranes bidirectionally and involves in a neurological disorder, neuromyelitis
      optica (NMO) caused by anti-AQP4 antibodies. Here, we developed a platform based
      on nanovesicle-carbon nanotube hybrid nanostructures for the real-time detection
      of anti-AQP4 antibodies and the electrophysiological monitoring of AQP4
      activities. Using the hybrid device, we could detect anti-AQP4 antibodies with a
      high sensitivity and estimate the binding constants under different osmotic
      conditions. The results show AQP4 had a better affinity to anti-AQP4 antibodies
      under hyper-osmotic conditions than normal conditions. Furthermore, our device
      can be utilized to study the real-time cellular responses related with AQP4 such
      as those to different osmotic stresses. This nanovesicle-based platform can be a
      simple but versatile tool for basic research about AQP4 and related biomedical
      applications such as disease diagnostics. 

PMID- 24874658
TI  - Amperometric detection of catechol using tyrosinase modified electrodes enhanced
      by the layer-by-layer assembly of gold nanocubes and polyelectrolytes.
AB  - A novel amperometric biosensor for catechol was developed using the layer-by
      layer (LbL) self-assembly of positively charged hexadecyltrimethylammonium
      stabilized gold nanocubes (AuNCs), negatively charged poly(sodium 4
      styrenesulfonate) and tyrosinase on a screen printed carbon electrode (SPCE). A
      carboxylic acid terminated alkanethiol assembled on electrochemically deposited
      Au nanoparticles on a SPCE was used as a platform for LbL assembly. Each SPCE
      sensor surface was terminated with tyrosinase and the electrocatalytic response
      due to the tyrosinase reaction with catechol was measured using cyclic
      voltammetry and square wave voltammetry (SWV). The effect of introducing AuNCs
      into the LbL assembly to further enhance the catechol detection performance was
      then investigated by comparing the SWV results to those from biosensors created
      using both the tyrosinase modified LbL assembly in the absence of NCs and the
      covalent attachment of tyrosinase. A wide dynamic range from 10nM to 80 uM of
      catechol with an excellent sensitivity of 13.72 A/M and a detection limit of 0.4
      nM were both achieved alongside a good selectivity and reproducibility for the
      AuNC-modified electrodes. As a demonstration, the optimized biosensor design was
      applied to determine catechol concentrations in tea samples.

PMID- 24874659
TI  - Synthetic immunosurveillance systems: nanodevices to monitor physiological
      events.
AB  - The field of nanotechnology has recently seen vast advancements in its
      applications for therapeutic strategy. This technological revolution has led way
      to nanomedicine, which spurred the development of clever drug delivery designs
      and ingenious nanovehicles for the monitoring of cellular events in vivo. The
      clinical implementations of this technology are innumerable and have demonstrated
      utility as diagnostic tools and fortifying machineries for the mammalian immune
      system. Recently engineered viral vectors and multi-subunit packaging RNAs have
      verified stable enough for long-term existence in the physiological environment
      and therefore reveal unique potential as artificial immunosurveillance devices.
      Physiological and pathological events recorded by nanodevices could help develop
      "biocatalogs" of patients' infection history, frequency of disease, and much
      more. In this article, we introduce a novel design concept for a multilayer
      synthetic immune network parallel to the natural immune system; an artificial
      network of continuously patrolling nanodevices incorporated in the blood and
      lymphatic systems, and adapted for molecular event recording, anomaly detection,
      drug delivery, and gene silencing. We also aim to discuss the approaches and
      advances recently reported in nanomedicine, especially as it pertains to
      promising viral and RNA-based nanovehicles and their prospective applications for
      the development of a synthetic immunosurveillance system (SIS). Alternative
      suggestions and limitations of these technologies are also discussed.

PMID- 24874660
TI  - Development of nanobody-based flow injection chemiluminescence immunoassay for
      sensitive detection of human prealbumin.
AB  - Nanobodies, derived from camelid heavy-chain antibodies, have novel and impactful
      applications in clinical diagnostics. Our objective is to develop a nanobody
      based chemiluminescence immunoassay for sensitive detection of human prealbumin
      (PA). In this context, a phage display nanobody library is constructed via
      immunizing dromedary camel with human prealbumin. Three nanobodies have been
      identified by five successive bio-panning steps. Based on their high expression
      level and good affinity, two out of three are chosen for further study. Magnetic
      beads (MBs) were functionalized with PEI by acylamide bond formed between the
      carboxyl group on the surface of the MB. Then, an anti-PA nanobody (Nb1) can be
      effectively immobilized onto the surface of the functionalized MB using
      glutaradehyde as the link. The modified MBs with Nb1 can specifically capture the
      target PA and reacted with silica nanoparticles with co-immobilized HRP and anti
      PA nanobody (Nb2). The concentration of PA was detected by flow injection
      chemiluminescence. When using MB/PEI as the carrier of anti-PA Nb1, the CL signal
      significantly increased to 4-fold compared with the signal using MB without PEI
      modification. The CL signal was further amplified to 5-fold when Si/Nb2 was used
      as the signal probe. Under optimized conditions, the present immunoassay
      exhibited a wide quantitative range from 0.05 to 1000 MUg L(-1) with a detection
      limit of 0.01 MUg L(-1). The sensitivity of the proposed immunoassay offers great
      promises in providing a sensitive, specific, time saving, and potential method
      for detecting PA in clinical settings.

PMID- 24874662
TI  - Complete genome sequence of canine papillomavirus type 11.
AB  - Papillomaviruses with the features of epitheliotropic, nonenveloped, circular,
      and double-stranded DNA belong to the family Papillomaviridae, which contributes
      to benign and malignant tumors in humans and animals. We report the whole-genome
      sequence of canine papillomavirus type 11 found at a pigmented plaque located on
      the skin of a mixed-breed bloodhound. 

PMID- 24874661
TI  - Bacteria in the adventitia of cardiovascular disease patients with and without
      rheumatoid arthritis.
AB  - The incidence of atherosclerosis is significantly increased in rheumatoid
      arthritis (RA). Infection is one factor that may be involved in the pathogenesis
      of both diseases. The cause of RA and atherosclerosis is unknown, and infection
      is one of the factors that may be involved in the pathogenesis of both diseases.
      The aims of this study were to identify bacteria in the aortic adventitia of
      patients with cardiovascular disease (CVD) in the presence and absence of RA, and
      to determine the effect of identified candidate pathogens on Toll-like receptor
      (TLR)-dependent signalling and the proinflammatory response. The aortic
      adventitia of 11 CVD patients with RA (RA+CVD) and 11 CVD patients without RA
      (CVD) were collected during coronary artery bypass graft surgery. Bacteria were
      detected in four samples from CVD patients and three samples from RA+CVD patients
      and identified by 16S rRNA gene sequencing. Methylobacterium oryzae was
      identified in all three RA+CVD samples, representing 44.1% of the bacterial
      flora. The effect of M. oryzae on TLR-dependent signalling was determined by
      transfection of HEK-293 cells. Although mild TLR2 signalling was observed, TLR4
      was insensitive to M. oryzae. Human primary macrophages were infected with M.
      oryzae, and a TLDA qPCR array targeting 90 genes involved in inflammation and
      immune regulation was used to profile the transcriptional response. A significant
      proinflammatory response was observed, with many of the up-regulated genes
      encoding proinflammatory cytokines (IL-1alpha, IL-1beta, IL-6, TNF-alpha) and
      chemokines (CCR7, IL-8). The aortic adventitia of CVD patients contains a wide
      range of bacterial species, and the bacterial flora is significantly less diverse
      in RA+CVD than CVD patients. M. oryzae may stimulate an proinflammatory response
      that may aggravate and perpetuate the pathological processes underlying
      atherosclerosis in RA patients. 

PMID- 24874663
TI  - Genome Sequence of the Native Apiculate Wine Yeast Hanseniaspora vineae T02/19AF.
AB  - The use of novel yeast strains for winemaking improves quality and provides
      variety including subtle characteristic differences in fine wines. Here we report
      the first genome of a yeast strain native to Uruguay, Hanseniaspora vineae
      T02/19AF, which has been shown to positively contribute to aroma and wine
      quality. 

PMID- 24874664
TI  - Metagenomic approach for understanding microbial population from petroleum muck.
AB  - Petroleum products play a major role in fueling the economy of the world but the
      pollution they create has become a critical issue. Understanding the diversity
      present in pipeline muck will help with the exploration of new microbial strains
      with better hydrocarbon degrading capacities for bioremediation of polluted
      sites. This study provides an analysis of petroleum muck using next generation
      sequencing. 

PMID- 24874665
TI  - Complete Genome Sequences of Two Citrobacter rodentium Bacteriophages, CR8 and
      CR44b.
AB  - The complete genomes of two virulent phages infecting Citrobacter rodentium are
      reported here for the first time. Both bacteriophages were isolated from local
      sewage treatment plant effluents. Genome analyses revealed a close relationship
      between both phages and allowed their classification as members of the
      Autographivirinae subfamily in the T7-like genus. 

PMID- 24874666
TI  - Complete genome sequences of nine mycobacteriophages.
AB  - Genome analyses of a large number of mycobacteriophages, bacterial viruses that
      infect members of the genus Mycobacterium, yielded novel enzymes and tools for
      the genetic manipulation of mycobacteria. We report here the complete genome
      sequences of nine mycobacteriophages, including a new singleton, isolated using
      Mycobacterium smegmatis mc(2)155 as a host strain. 

PMID- 24874667
TI  - Genome Sequencing of Ralstonia solanacearum Biovar 3, Phylotype I, Strains Rs-09
      161 and Rs-10-244, Isolated from Eggplant and Chili in India.
AB  - Ralstonia solanacearum Indian strains Rs-09-161 and Rs-10-244 were isolated from
      the coastal region of Goa and from the Andaman Islands. We report the draft
      genome sequences of these representative isolates infecting solanaceous
      vegetables in India. 

PMID- 24874668
TI  - Full-genome sequence of human betacoronavirus 2c jordan-n3/2012 after serial
      passage in Mammalian cells.
AB  - Middle East respiratory syndrome coronavirus (MERS-CoV) is the etiologic agent of
      a highly lethal pneumonia. Here, we report the full-genome sequence of the Jordan
      N3/2012 strain after serial passage in two distinct mammalian cell lines. The
      genome exhibits noteworthy stability, which may inform the development of
      vaccines and therapeutics used to treat infection with this virus. 

PMID- 24874669
TI  - Draft Genome Sequence of Enterobacter cloacae Strain JD6301.
AB  - Enterobacter cloacae strain JD6301 was isolated from a mixed culture with
      wastewater collected from a municipal treatment facility and oleaginous
      microorganisms. A draft genome sequence of this organism indicates that it has a
      genome size of 4,772,910 bp, an average G+C content of 53%, and 4,509 protein
      coding genes. 

PMID- 24874671
TI  - Genome Sequence of the Novel Reassortant Mammalian Orthoreovirus Strain
      MRV00304/13, Isolated from a Calf with Diarrhea from the United States.
AB  - Mammalian orthoreovirus (MRV) strain MRV00304/13 was isolated from diarrheic
      calves. The serotype-specific antigen sigma1 was found to be 95% identical to
      that of bovine MRV1. All predicted viral proteins had >92% identity to those of
      MRV except u2 and sigma1s (80 and 72% identities, respectively), suggesting that
      MRV00304/13 is a novel reassortant MRV1. 

PMID- 24874670
TI  - Draft Whole-Genome Sequence of a New Variant of Vibrio cholerae O1 El Tor Strain
      Isolated from a Cholera Patient in Russia.
AB  - Draft whole-genome sequencing of the Vibrio cholerae O1 El Tor clinical strain
      L3226, isolated in Moscow in 2010, was carried out. Various mutations in the
      virulence-associated mobile elements were determined in its genome that
      differentiated this strain from the reference V. cholerae O1 El Tor strain
      N16961. 

PMID- 24874672
TI  - Draft Genome Sequence of blaNDM-1-Positive Escherichia coli O25b-ST131 Clone
      Isolated from an Environmental Sample.
AB  - A multidrug-resistant NDM-1 carbapenamase-producing Escherichia coli sequence
      type 131 (ST131) organism was obtained from vacuum cleaner dust collected from
      the home of a case patient. Here, we report the assembly and annotation of its
      genome. 

PMID- 24874673
TI  - Genome Sequence of Sporolactobacillus terrae DSM 11697, the Type Strain of the
      Species.
AB  - Sporolactobacillus terrae DSM 11697 is the type strain of S. terrae. Here, we
      present a 3.2-Mb assembly of its genome sequence. As S. terrae is one of the
      important lactic acid bacteria, the genome sequence may provide insights into the
      molecular mechanism for its further microbial investigation. 

PMID- 24874675
TI  - Draft Genome Sequence of Lactobacillus animalis 381-IL-28.
AB  - Lactobacillus animalis 381-IL-28 is an integral component of a multistrain
      commercial culture with food biopreservative and pathogen biocontrol
      functionality. A draft sequence of the L. animalis 381-IL-28 genome is described
      in this paper. 

PMID- 24874674
TI  - Draft Genome Sequence of Bacillus cereus Strain BcFL2013, a Clinical Isolate
      Similar to G9241.
AB  - Bacillus cereus strains, such as G9241, causing anthrax-like illnesses have
      recently been discovered. We report the genome sequence of a clinical strain, B.
      cereus BcFL2013, which is similar to G9241, recovered from a patient in Florida. 

PMID- 24874676
TI  - Complete genome sequence of classical Swine Fever virus genotype 2.2 strain
      bergen.
AB  - The complete genome sequence of the genotype 2.2 classical swine fever virus
      strain Bergen has been determined; this strain was originally isolated from
      persistently infected domestic pigs in the Netherlands and is characterized to be
      of low virulence. 

PMID- 24874677
TI  - Complete Genome Sequence of Winogradskyella sp. Strain PG-2, a Proteorhodopsin
      Containing Marine Flavobacterium.
AB  - Winogradskyella sp. strain PG-2 is a marine flavobacterium isolated from surface
      seawater. This organism contains proteorhodopsin, which can convert light energy
      into available forms of biochemical energy. Here, we present its complete genome
      sequence and annotation, which provide further insights into the life strategy of
      proteorhodopsin-mediated phototrophy in the ocean. 

PMID- 24874678
TI  - Draft Genome Sequence of Raoultella ornithinolytica TNT, a Trinitrotoluene
      Denitrating and Plant Growth-Promoting Strain Isolated from Explosive
      Contaminated Soil.
AB  - We report the draft genome of Raoultella ornithinolytica TNT, a Gram-negative
      bacterium of the Enterobacteriaceae isolated from military soil in Belgium.
      Strain TNT uses nitrite released from trinitrotoluene (TNT) for growth and is a
      potent plant growth promoter. An analysis of its 5.6-Mb draft genome will bring
      insights into TNT degradation-reinforcing bioremediation applications. 

PMID- 24874679
TI  - Genome Sequence of Bacillus cereus Strain A1, an Efficient Starch-Utilizing
      Producer of Hydrogen.
AB  - Bacillus cereus strain A1 is a newly isolated hydrogen producer capable of
      utilizing bioresources and biowaste, such as starch and starch wastewater. Here,
      we present a 5.67-Mb assembly of the genome sequence of strain A1, which may
      provide insights into the molecular mechanism of hydrogen production from
      bioresources and biowaste. 

PMID- 24874680
TI  - Draft Genome Sequence of the Field Isolate Brucella melitensis Strain Bm IND1
      from India.
AB  - Brucella spp. are facultative intracellular bacterial pathogens causing the
      zoonotic disease brucellosis. Here, we report the draft genome sequence of the
      Brucella melitensis strain from India designated Bm IND1, isolated from stomach
      contents of an aborted goat fetus. 

PMID- 24874681
TI  - Draft Genome Sequence of Mycobacterium triplex DSM 44626.
AB  - We announce the draft genome sequence of Mycobacterium triplex strain DSM 44626,
      a nontuberculosis species responsible for opportunistic infections. The genome
      described here is composed of 6,382,840 bp, with a G+C content of 66.57%, and
      contains 5,988 protein-coding genes and 81 RNA genes. 

PMID- 24874683
TI  - Complete Genome Sequence of the Subsurface, Mesophilic Sulfate-Reducing Bacterium
      Desulfovibrio aespoeensis Aspo-2.
AB  - Desulfovibrio aespoeensis Aspo-2, DSM 10631(T), is a mesophilic, hydrogenotrophic
      sulfate-reducing bacterium sampled from a 600-m-deep subsurface aquifer in hard
      rock under the island of Aspo in southeastern Sweden. We report the genome
      sequence of this bacterium, which is a 3,629,109-bp chromosome; plasmids were not
      found. 

PMID- 24874682
TI  - Complete Genome Sequence of K14JB01, a Novel Variant Strain of Porcine Epidemic
      Diarrhea Virus in South Korea.
AB  - A novel variant strain of porcine epidemic diarrhea virus (PEDV) emerged on pig
      farms in South Korea during late 2013. Genomic DNA isolated from a K14JB01 strain
      identified in a diarrheal pig showed high sequence similarity to PEDV strains
      prevailing in the United States in 2013. This is the first study to identify the
      complete genome sequence of a novel variant PEDV in South Korea. 

PMID- 24874684
TI  - Complete Genome Sequence of the Attenuated Novobiocin-Resistant Streptococcus
      iniae Vaccine Strain ISNO.
AB  - Streptococcus iniae ISNO is an attenuated novobiocin-resistant vaccine strain.
      Its full genome is 2,070,182 bp in length. The availability of this genome will
      allow comparative genomics to identify potential virulence genes important for
      pathogenesis of S. iniae and potential mechanisms associated with novobiocin
      resistance in this strain. 

PMID- 24874685
TI  - Comparative Genomic Analysis of Two Multidrug-Resistant Clinical Isolates of
      ST395 Epidemic Strain of Pseudomonas aeruginosa Obtained 12 Years Apart.
AB  - Pseudomonas aeruginosa can cause large and prolonged outbreaks in hospitals. We
      have sequenced and annotated the genomes of two multidrug-resistant P. aeruginosa
      isolates from the same strain obtained 12 years apart from different patients.
      Genomic analysis provided insight on the genes acquired and lost by P. aeruginosa
      during its spread. 

PMID- 24874686
TI  - Draft Genome Sequence of Bacillus thuringiensis Strain LM1212, Isolated from the
      Cadaver of an Oryctes gigas Larva in Madagascar.
AB  - We report the draft genome sequence of Bacillus thuringiensis strain LM1212,
      which differentiates into crystal producers or spore formers during the
      stationary phase. Availability of this genome sequence will facilitate the study
      of spore formation, crystal formation, cell differentiation, and evolution of B.
      thuringiensis. 

PMID- 24874687
TI  - Draft Genome Sequence of Frankia sp. Strain BMG5.23, a Salt-Tolerant Nitrogen
      Fixing Actinobacterium Isolated from the Root Nodules of Casuarina glauca Grown
      in Tunisia.
AB  - Nitrogen-fixing actinobacteria of the genus Frankia are symbionts of woody
      dicotyledonous plants termed actinorhizal plants. We report here a 5.27-Mbp draft
      genome sequence for Frankia sp. strain BMG5.23, a salt-tolerant nitrogen-fixing
      actinobacterium isolated from root nodules of Casuarina glauca collected in
      Tunisia. 

PMID- 24874688
TI  - Draft Genome Sequence of Mycobacterium farcinogenes NCTC 10955.
AB  - We report the draft genome sequence of Mycobacterium farcinogenes NCTC 10955
      (=DSM 43637(T)), a nontuberculosis species responsible for bovine farcy. The
      strain described here is composed of 6,139,893 bp, with a G+C content of 65.73%,
      and contains 5,816 protein-coding genes and 76 RNA genes. 

PMID- 24874689
TI  - Complete Genome Sequences of Pseudomonas monteilii SB3078 and SB3101, Two Benzene
      , Toluene-, and Ethylbenzene-Degrading Bacteria Used for Bioaugmentation.
AB  - Pseudomonas monteilii SB3078 and SB3101 are benzene-, toluene-, and ethylbenzene
      degrading strains used for bioaugmentation in relation to treatment of wastewater
      contaminated with petrochemical hydrocarbons. Complete genome sequencing of the
      bioaugmentation strains confirms that they are very closely related (100.0%
      average nucleotide identity). Both strains contain extensive integration of phage
      elements, with the main difference being insertion of additional phage elements
      in the SB3078 genome. 

PMID- 24874690
TI  - Complete Genome of Rhodococcus pyridinivorans SB3094, a Methyl-Ethyl-Ketone
      Degrading Bacterium Used for Bioaugmentation.
AB  - Here, we present the complete genome of Rhodococcus pyridinivorans SB3094, a
      methyl-ethyl-ketone (MEK)-degrading strain used for bioaugmentation relating to
      the treatment of wastewater contamination with petrochemical hydrocarbons. The
      genome highlights important features for bioaugmentation, including the genes
      involved in the degradation of MEK. 

PMID- 24874691
TI  - Draft Genome Sequence of Methicillin-Resistant Staphylococcus epidermidis Strain
      ET-024, Isolated from an Endotracheal Tube Biofilm of a Mechanically Ventilated
      Patient.
AB  - Staphylococcus epidermidis strain ET-024 was isolated from a biofilm on an
      endotracheal tube of a mechanically ventilated patient. This strain is resistant
      to methicillin, and the draft genome sequence shares some characteristics with
      other nosocomial S. epidermidis strains (such as S. epidermidis RP62A). 

PMID- 24874692
TI  - Stress and anxiety in women with gestational diabetes during dietary management.
AB  - PURPOSE: To explore the stress and anxiety experiences during dietary management
      in women with gestational diabetes (GDM). METHODS: Thirty women with GDM from the
      Winnipeg area participated in the mixed methods study. Each participant completed
      a Food Choice Map semistructured interview, a Perceived Stress Scale, a Pregnancy
      Anxiety Scale, a State-Trait Anxiety Inventory-Trait questionnaire, and a
      demographic questionnaire. Stress and anxiety experiences were identified from
      interview transcripts and categorized into themes based on the constant
      comparative method. Questionnaire scores aided in interpreting the stress and
      anxiety experience in the qualitative data. RESULTS: Three major themes were
      generated from the interviews: (1) stress related to GDM diagnosis and the
      perception of a high risk pregnancy; (2) stress over losing control of GDM during
      the process of dietary management; and (3) anxiety related to the fear of
      maternal and infant complications. Women on insulin experienced significantly
      higher levels of perceived stress (P < .01), and the dietary management stress
      was more prevalent in women using insulin compared to the ones on diet treatment
      only (Fisher exact test, P < .01). Unhealthy diet coping strategies occurred with
      the stress and anxiety. CONCLUSIONS: Stress and anxiety were associated with
      different contexts in this study sample. Women who were on insulin experienced
      significantly higher levels of perceived stress related to dietary management.

PMID- 24874694
TI  - Exploration of the dynamic properties of protein complexes predicted from
      spatially constrained protein-protein interaction networks.
AB  - Protein complexes are not static, but rather highly dynamic with subunits that
      undergo 1-dimensional diffusion with respect to each other. Interactions within
      protein complexes are modulated through regulatory inputs that alter interactions
      and introduce new components and deplete existing components through exchange.
      While it is clear that the structure and function of any given protein complex is
      coupled to its dynamical properties, it remains a challenge to predict the
      possible conformations that complexes can adopt. Protein-fragment Complementation
      Assays detect physical interactions between protein pairs constrained to <=8 nm
      from each other in living cells. This method has been used to build networks
      composed of 1000s of pair-wise interactions. Significantly, these networks
      contain a wealth of dynamic information, as the assay is fully reversible and the
      proteins are expressed in their natural context. In this study, we describe a
      method that extracts this valuable information in the form of predicted
      conformations, allowing the user to explore the conformational landscape, to
      search for structures that correlate with an activity state, and estimate the
      abundance of conformations in the living cell. The generator is based on a Markov
      Chain Monte Carlo simulation that uses the interaction dataset as input and is
      constrained by the physical resolution of the assay. We applied this method to an
      18-member protein complex composed of the seven core proteins of the budding
      yeast Arp2/3 complex and 11 associated regulators and effector proteins. We
      generated 20,480 output structures and identified conformational states using
      principle component analysis. We interrogated the conformation landscape and
      found evidence of symmetry breaking, a mixture of likely active and inactive
      conformational states and dynamic exchange of the core protein Arc15 between core
      and regulatory components. Our method provides a novel tool for prediction and
      visualization of the hidden dynamics within protein interaction networks. 

PMID- 24874695
TI  - Is vascular imaging valuable prior to administration of intravenous tissue
      plasminogen activator?
AB  - Our goals were to explore whether performing computerized tomography angiography
      (CTA) prior to administration of tissue plasminogen activator (tPA) delays
      treatment and impacts outcome in patients with proximal middle cerebral artery
      occlusions (pMCAO). Patients with pMCAO with a National Institutes of Health
      Stroke scale (NIHSS) score >10 were identified from a prospective Stroke
      Registry. Patients underwent multi-parametric imaging studies whenever possible.
      Patients who underwent CTA were compared to those who only had non-contrast CT
      scan. Disability was measured with the modified Rankin Scale. Logistic regression
      was used to determine outcome modifiers. We included 73 patients (median age 73
      years, 52% men) with moderate-severe stroke (median admission NIHSS 14). Of
      those, 44 underwent CTA and 29 did not. There were no differences between the
      groups in risk factor profile or baseline characteristics including stroke
      severity and door to needle, door to imaging or imaging to treatment times. At 90
      days post-stroke there were no statistically significant differences in outcomes
      between the groups. On multivariate analysis, performing CTA had no impact on the
      chance of obtaining favorable outcome. In conclusion, CTA does not have a major
      impact on outcome in patients with pMCAO treated with tPA. Therefore, performing
      CTA should be considered on an individual basis prior to administration of tPA.

PMID- 24874696
TI  - Mefloquine improved progressive multifocal leukoencephalopathy in a patient with
      immunoglobulin A nephropathy.
AB  - We describe a patient with immunoglobulin A nephropathy who was diagnosed with
      progressive multifocal leukoencephalopathy (PML) and successfully treated with
      mefloquine, an antimalarial medication. A 67-year-old man with immunoglobulin A
      nephropathy presented to the hospital emergency room with fever and generalized
      tonic-clonic seizure. Cerebrospinal fluid (CSF) nested polymerase chain reaction
      (PCR) was positive for John Cunningham virus and brain MRI displayed high signal
      intensity in the white matter in the right parietal lobe without gadolinium
      enhancement. Tapering of prednisone did not arrest the disease progression and a
      new lesion was detected on the cerebellum. Administration of mefloquine stopped
      lesion progression and resulted in dramatic clinical improvement. The CSF nested
      PCR for the John Cunningham virus also became negative. In reviewing the
      literature, mefloquine has had a heterogeneous effect in PML patients, and P
      glycoprotein polymorphism and proper dosage could contribute to the various
      effects seen. Mefloquine may be a favorable treatment option in some patients
      with PML, and P-glycoprotein polymorphism may play an important role in its
      efficacy. More large studies in other ethnic groups including polymorphism
      studies for the gene encoding P-glycoprotein (ABCB1/MDR1) and taking into account
      various underlying conditions with secondary immunosuppression should be carried
      out to investigate whether mefloquine is effective for treating PML.

PMID- 24874693
TI  - Mimicking the germinal center reaction in hybridoma cells to isolate temperature
      selective anti-PEG antibodies.
AB  - Modification of antibody class and binding properties typically requires cloning
      of antibody genes, antibody library construction, phage or yeast display and
      recombinant antibody expression. Here, we describe an alternative "cloning-free"
      approach to generate antibodies with altered antigen-binding and heavy chain
      isotype by mimicking the germinal center reaction in antibody-secreting hybridoma
      cells. This was accomplished by lentiviral transduction and controllable
      expression of activation-induced cytidine deaminase (AID) to generate somatic
      hypermutation and class switch recombination in antibody genes coupled with high
      throughput fluorescence-activated cell sorting (FACS) of hybridoma cells to
      detect altered antibody binding properties. Starting from a single established
      hybridoma clone, we isolated mutated antibodies that bind to a low-temperature
      structure of polyethylene glycol (PEG), a polymer widely used in nanotechnology,
      biotechnology and pharmaceuticals. FACS of AID-infected hybridoma cells also
      facilitated rapid identification of class switched variants of monoclonal IgM to
      monoclonal IgG. Mimicking the germinal center reaction in hybridoma cells may
      offer a general method to identify and isolate antibodies with altered binding
      properties and class-switched heavy chains without the need to carry out DNA
      library construction, antibody engineering and recombinant protein expression. 

PMID- 24874698
TI  - On the potential application of superalkali clusters in designing novel alkalides
      with large nonlinear optical properties.
AB  - A new series of superalkali-based alkalides, i.e., Li3(+)(calix[4]pyrrole)M(-),
      Li3O(+)(calix[4]pyrrole)M(-), and M3O(+)(calix[4]pyrrole)K(-) (M = Li, Na, and
      K), have been theoretically designed and investigated by means of density
      functional theory computations. These species have diverse structural isomers, in
      which the embedded superalkali units maintain their identities and prefer the
      horizontal orientation over the vertical one. All the proposed alkalides exhibit
      considerable first hyperpolarizabilities (beta0) up to 34,718 au. Especially, a
      prominent M(-) atomic number dependence of (hyper)polarizabilities is observed
      for the Li3(+)(calix[4]pyrrole)M(-) and Li3O(+)(calix[4]pyrrole)M(-) compounds.
      Besides, the dependence of the nonlinear optical response of such alkalides on
      the species of involved superalkalis is also investigated. We hope that this work
      will promote further application of superalkalis and, on the other hand, attract
      more research interest and efforts in exploring new, unconventional alkalides.

PMID- 24874697
TI  - Olanzapine-induced restless legs syndrome.
AB  - Only nine patients with olanzapine-induced restless legs syndrome (RLS) have been
      reported in the literature to our knowledge. We describe two patients with
      olanzapine-induced RLS treated at our hospital and review the nine reported
      patients. There were five women and six men aged between 28 and 62 years in the
      overall group. RLS symptoms emerged at olanzapine doses between 2.5 and 20mg. The
      symptoms improved in all patients when the dose was reduced and immediately
      disappeared when the medication was stopped. International Restless Legs Scale
      (IRLS) scores ranged from 10 to 35. Three patients had a family history of
      idiopathic RLS. Supplemental drugs were administered to control RLS symptoms in
      five patients. Ropinirole was effective in one patient, while two patients did
      not respond to the drug. Propoxyphene effectively relieved symptoms in one
      patient who did not respond to ropinirole or clonazepam. RLS symptoms did not
      recur following substitution of other antipsychotic drugs for olanzapine. In
      conclusion, olanzapine can induce RLS, particularly in patients with a family
      history of idiopathic RLS. More than half of the patients experienced severe to
      very severe symptoms. A dose-dependent relationship was observed between
      olanzapine and RLS symptoms. A gradual increase in dose may prevent olanzapine
      induced RLS. The optimal treatment for olanzapine-induced RLS is discontinuation
      of olanzapine.

PMID- 24874699
TI  - Label-free monitoring of MU-opioid receptor-mediated signaling.
AB  - In this study, we used a combination of traditional signaling investigation
      approaches, bioluminescence resonance energy transfer (BRET) biosensors, and the
      label-free approach surface plasmon resonance (SPR) spectroscopy to monitor the
      signaling cascades of the MU-opioid receptor (MOP). In human embryonic kidney
      cells stably expressing a Flag-tagged version of human MOP, we compared the
      signals triggered by the noninternalizing and internalizing MOP agonists morphine
      and DAMGO (Tyr-D-Ala-Gly-N-methyl-Phe-Gly-ol), respectively. We studied three
      major and well described components of MOP signaling: receptor internalization, G
      protein coupling, and activation of extracellular signal-regulated kinase
      ERK1/ERK2. Our results show that morphine and DAMGO display different profiles of
      receptor internalization and a similar ability to trigger the phosphorylation of
      ERK1/ERK2. Our SPR analyses revealed that morphine and DAMGO evoke similar SPR
      signatures and that Galphai, cAMP-dependent pathways, and ERK1/ERK2 have key
      roles in morphine- and DAMGO-mediated signaling. Most interestingly, we found
      that the so-called MOP neutral antagonists CTOP (D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen
      Thr-NH(2)), naloxone, and naltrexone behave like partial agonists. Even more
      intriguing, BRET experiments indicate that CTAP (D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen
      Thr-NH(2)) induces similar conformational changes as naltrexone at the Galphai
      betagamma interface, whereas it appears as an inverse agonist based on its SPR
      response thus indicating distinct signaling mechanisms for the two ligands. Taken
      together, our results support the usefulness of label-free methods such as SPR to
      study whole-cell responses and signaling cascades triggered by G protein-coupled
      receptors and complement the conventional approaches by revealing cellular
      responses that would have been otherwise undetectable.

PMID- 24874700
TI  - Sharing individual participant data from clinical trials: an opinion survey
      regarding the establishment of a central repository.
AB  - BACKGROUND: Calls have been made for increased access to individual participant
      data (IPD) from clinical trials, to ensure that complete evidence is available.
      However, despite the obvious benefits, progress towards this is frustratingly
      slow. In the meantime, many systematic reviews have already collected IPD from
      clinical trials. We propose that a central repository for these IPD should be
      established to ensure that these datasets are safeguarded and made available for
      use by others, building on the strengths and advantages of the collaborative
      groups that have been brought together in developing the datasets. OBJECTIVE:
      Evaluate the level of support, and identify major issues, for establishing a
      central repository of IPD. DESIGN: On-line survey with email reminders.
      PARTICIPANTS: 71 reviewers affiliated with the Cochrane Collaboration's IPD Meta
      analysis Methods Group were invited to participate. RESULTS: 30 (42%) invitees
      responded: 28 (93%) had been involved in an IPD review and 24 (80%) had been
      involved in a randomised trial. 25 (83%) agreed that a central repository was a
      good idea and 25 (83%) agreed that they would provide their IPD for central
      storage. Several benefits of a central repository were noted: safeguarding and
      standardisation of data, increased efficiency of IPD meta-analyses, knowledge
      advancement, and facilitating future clinical, and methodological research. The
      main concerns were gaining permission from trial data owners, uncertainty about
      the purpose of the repository, potential resource implications, and increased
      workload for IPD reviewers. Restricted access requiring approval, data security,
      anonymisation of data, and oversight committees were highlighted as issues under
      governance of the repository. CONCLUSION: There is support in this community of
      IPD reviewers, many of whom are also involved in clinical trials, for storing IPD
      in a central repository. Results from this survey are informing further work on
      developing a repository of IPD which is currently underway by our group.

PMID- 24874701
TI  - Eruption stage of permanent molars and occlusal caries activity/arrest.
AB  - This study assessed the association between the eruption stage of permanent
      second molars and occlusal caries activity among 12-year-old schoolchildren from
      South Brazil. A cross-sectional study was performed in Porto Alegre using a
      multistage probability sampling strategy to select a representative sample.
      Clinical examination was conducted to assess the eruption stage of permanent
      molars, Gingival Bleeding Index, and, after tooth cleaning and drying, caries
      experience (noncavitated and cavitated lesions, including caries activity
      assessment). Data were collected on sex, socioeconomic status, mother's
      education, brushing frequency, and consumption of soft drinks. Generalized
      estimating equations were used to estimate odds ratios (ORs) and 95% confidence
      intervals (CIs). Overall, 983 schoolchildren with 3,071 second molars were
      available for analysis. Whereas active caries was observed in 6.6% of fully
      erupted permanent second molars, caries affected 26.2%, 29.6%, and 18.2% of
      erupting molars classified as stages 1, 2, and 3, respectively: stage 1,
      partially erupted occlusal surface; stage 2, fully erupted occlusal surface, <1/2
      crown exposed; and stage 3, fully erupted occlusal surface, >1/2 crown exposed.
      After adjusting for socioeconomic and behavioral variables, partially erupted
      molars were significantly more likely to present active caries lesions than
      molars in full occlusion: stage 1, OR = 4.99 (95% CI = 3.38, 7.38); stage 2, OR =
      5.18 (95% CI = 3.14, 8.53); stage 3, OR = 3.20 (95% CI = 2.21, 4.64). Similar
      results were found when clinical variables were included in the adjusted model.
      In conclusion, most occlusal caries lesions tend to arrest/revert when teeth
      reach the occlusal plan; however, an important proportion of these lesions
      remains active and in need of proper management. Children at risk should be
      targeted with preventive and minimally invasive strategies. 

PMID- 24874702
TI  - Porphyromonas gingivalis-mediated Epithelial Cell Entry of HIV-1.
AB  - HIV-1 relies on the host's cell machinery to establish a successful infection.
      Surface receptors, such as CD4, CCR5, and CXCR4 of T cells and macrophages, are
      essential for membrane fusion of HIV-1, an initiate step in viral entry. However,
      it is not well defined how HIV-1 infects CD4-negative mucosal epithelial cells.
      Here we show that there is a specific interaction between HIV-1 and an invasive
      oral bacterium, Porphyromonas gingivalis. We found that HIV-1 was trapped on the
      bacterial surface, which led to internalization of HIV-1 virions as the bacteria
      invaded CD4-negative epithelial cells. Both bacterial and viral DNA was detected
      in HeLa and TERT-2 cells exposed to the HIV-1-P. gingivalis complexes 2 hr after
      the initial infection but not in cells exposed to HIV-1 alone. Moreover,
      epithelial cell entry of HIV-1 was positively correlated with invasive activity
      of the P. gingivalis strains tested, even when the binding affinities of HIV-1 to
      these strains were similar. Finally, it was demonstrated that the viral DNA was
      integrated into the genome of the host epithelial cells. These results reveal a
      receptor-independent HIV-1 entry into epithelial cells, which may be relevant in
      HIV transmission in other mucosal epithelia where complex microbial communities
      can be found. 

PMID- 24874703
TI  - Odor valence linearly modulates attractiveness, but not age assessment, of
      invariant facial features in a memory-based rating task.
AB  - Scented cosmetic products are used across cultures as a way to favorably
      influence one's appearance. While crossmodal effects of odor valence on perceived
      attractiveness of facial features have been demonstrated experimentally, it is
      unknown whether they represent a phenomenon specific to affective processing. In
      this experiment, we presented odors in the context of a face battery with
      systematic feature manipulations during a speeded response task. Modulatory
      effects of linear increases of odor valence were investigated by juxtaposing
      subsequent memory-based ratings tasks--one predominantly affective
      (attractiveness) and a second, cognitive (age). The linear modulation pattern
      observed for attractiveness was consistent with additive effects of face and odor
      appraisal. Effects of odor valence on age perception were not linearly modulated
      and may be the result of cognitive interference. Affective and cognitive
      processing of faces thus appear to differ in their susceptibility to modulation
      by odors, likely as a result of privileged access of olfactory stimuli to
      affective brain networks. These results are critically discussed with respect to
      potential biases introduced by the preceding speeded response task.

PMID- 24874706
TI  - Obese and lean Zucker rats respond similarly to intraperitoneal administration of
      gastrin-releasing peptides.
AB  - The Zucker rat is an animal model used to study obesity and the control of food
      intake by various satiety peptides. The amphibian peptide bombesin (Bn) reduces
      cumulative food intake similarly in both obese and lean weanling Zucker rats.
      Here, we hypothesized that intraperitoneal (i.p) administration of gastrin
      releasing peptides-10, -27 and -29 (GRP-10, GRP-27, GRP-29), which are the
      mammalian forms of Bn, would reduce first meal size (MS, 10% sucrose) and prolong
      the intermeal interval (IMI, time between first and second meals) similarly in
      obese and lean adult Zucker rats. To test this hypothesis, we administered GRP
      10, GRP-27 and GRP-29 (0, 2.1, 4.1 and 10.3 nmol/kg) i.p. to obese and lean male
      Zucker rats (who were deprived of overnight food but not water) and then measured
      the first and second MS, IMI and satiety ratio (SR, IMI/MS). We found that in
      both obese and lean rats, all forms of GRP reduced the first MS, and in lean
      rats, they also decreased the second MS. Additionally, GRP-10 and GRP-29
      prolonged the IMI in both obese and lean rats, but GRP-27 only prolonged it in
      lean rats. Finally, we found that all forms of GRP increased the SR in both obese
      and lean rats. In agreement with our hypothesis, we conclude that all forms of
      GRP reduce food intake in obese and lean adult Zucker rats similar to Bn in
      weanling rats.

PMID- 24874704
TI  - Biological properties of adrenomedullin conjugated with polyethylene glycol.
AB  - Adrenomedullin (AM) is a vasodilator peptide with pleiotropic effects, including
      cardiovascular protection and anti-inflammation. Because of these beneficial
      effects, AM appears to be a promising therapeutic tool for human diseases, while
      intravenous injection of AM stimulates sympathetic nerve activity due to short
      acting potent vasodilation, resulting in increased heart rate and renin
      secretion. To lessen these acute reactions, we conjugated the N-terminal of human
      AM peptide with polyethylene glycol (PEG), and examined the biological properties
      of PEGylated AM in the present study. PEGylated AM stimulated cAMP production, an
      intracellular second messenger of AM, in cultured human embryonic kidney cells
      expressing a specific AM receptor in a dose-dependent manner, as did native human
      AM. The pEC50 value of PEGylated AM was lower than human AM, but no difference
      was noted in maximum response (Emax) between the PEGylated and native peptides.
      Intravenous bolus injection of 10nmol/kg PEGylated AM lowered blood pressure in
      anesthetized rats, but the acute reduction became significantly smaller by
      PEGylation as compared with native AM. Plasma half-life of PEGylated AM was
      significantly longer than native AM both in the first and second phases in rats.
      In summary, N-terminal PEGylated AM stimulated cAMP production in vitro, showing
      lessened acute hypotensive action and a prolonged plasma half-life in comparison
      with native AM peptide in vivo. 

PMID- 24874705
TI  - Soluble DPP4 originates in part from bone marrow cells and not from the kidney.
AB  - Dipeptidyl peptidase 4 (DPP4) is known to inactivate incretins as well as
      important chemokines and neuropeptides. DPP4 is expressed as a transmembrane
      protein but also occurs as a soluble enzyme circulating in the blood. However,
      the origin of the soluble DPP4 (sDPP4) is still unknown. In this study, DPP4
      activity was quantified in plasma and extracted from different rat organs. Then,
      in order to see if the kidney or the bone marrow was the source of sDPP4, kidney
      or bone marrow transplantation was performed between wildtype (wt) Dark Agouti
      (DA) and DPP4 deficient congenic rats (n=6-9). Kidney was verified to have the
      highest DPP4 activity, followed by spleen and lung. In the following three weeks
      after successful kidney transplantation only transient trace plasma DPP4 activity
      was detected in DPP4 deficient rats receiving wt kidneys. In addition, DPP4
      activity was not diminished in DA wt rats receiving DPP4 deficient kidneys. Both
      findings indicated that sDPP4 did not originate from the kidney. In contrast,
      43+/-14% (compared to wt) sDPP4 activity was detected in the plasma of DPP4
      deficient DA rats that were reconstituted with wt bone marrow cells. Not only
      leukocyte but also macrophage subpopulations express DPP4 in bone marrow as well
      as in blood as assessed by flow cytometry. Thus, bone marrow derived cells but
      not the kidney represent at least one source of sDPP4. And leukocyte or
      macrophage subpopulations could be potential candidates. 

PMID- 24874708
TI  - Effects of PEGylated porcine glucagon-like peptide-2 therapy in weaning piglets
      challenged with lipopolysaccharide.
AB  - This study aims to evaluate the therapeutic effect of polyethylene glycosylated
      porcine glucagon-like peptide-2 (pGLP-2), a long-acting form of pGLP-2, in
      lipopolysaccharide (LPS)-challenged piglets. Eighteen 21-day-old weaning piglets
      were randomly assigned into three groups: control (saline solution), LPS (100
      MUg/kg LPS), and PEG-pGLP-2 (10 nmol/kg PEG-pGLP-2+100 MUg/kg LPS). All
      treatments were administered intraperitoneally. Compared with the control
      treatment, LPS treatment significantly decreased (P<0.05) the villus heights of
      the duodenum and jejunum, as well as the villus height/crypt depth ratio of the
      jejunum. However, PEG-pGLP-2 therapy reduced these effects (P>0.05).
      Specifically, PEG-pGLP-2 infusion significantly increased the villus height/crypt
      depth ratio of the duodenum (P<0.05) compared with LPS treatment. Compared with
      the control treatment, LPS treatment significantly increased (P<0.05) the mRNA
      expression levels of interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha
      (TNF-alpha) in the jejunum. However, PEG-pGLP-2 therapy reduced these effects
      (P<0.05). Specifically, PEG-pGLP-2 infusion significantly decreased (P<0.05) the
      mRNA expression levels of interleukin (IL)-8 and TNF-alpha in the duodenum and
      jejunum, IL-10 in the duodenum, and IFN-gamma in the jejunum compared with the
      LPS treatment. LPS treatment increased the caspase-3 activity of the ileum
      mucosal (P<0.05), and this effect was significantly reduced by PEG-pGLP-2
      treatment. These results indicate that PEG-pGLP-2 infusion alleviates the
      severity of intestinal injury in weaning piglets by reducing the secretion of
      inflammatory cytokines and the caspase-3 activity, and increasing the villus
      height/crypt depth ratio.

PMID- 24874707
TI  - Effects of sex and reproductive experience on the number of orexin A
      immunoreactive cells in the prairie vole brain.
AB  - Large populations of cells synthesizing the neuropeptide orexin (OX) exist in the
      caudal hypothalamus of all species examined and are implicated in physiological
      and behavioral processes including arousal, stress, anxiety and depression,
      reproduction, and goal-directed behaviors. Hypothalamic OX expression is sexually
      dimorphic in different directions in laboratory rats (F>M) and mice (M>F),
      suggesting different roles in male and female physiology and behavior that are
      species-specific. We here examined if the number of hypothalamic cells
      immunoreactive for orexin A (OXA) differs between male and female prairie voles
      (Microtus ochrogaster), a socially monogamous species that pairbonds after mating
      and in which both sexes care for offspring, and if reproductive experience
      influences their number of OXA-immunoreactive (OXA-ir) cells. It was found that
      the total number of OXA-ir cells did not differ between the sexes, but females
      had more OXA-ir cells than males in anterior levels of the caudal hypothalamus,
      while males had more OXA-ir cells posteriorly. Sexually experienced females
      sacrificed 12 days after the birth of their first litter, or one day after birth
      of a second litter, had more OXA-ir cells in anterior levels but not posterior
      levels of the caudal hypothalamus compared to females housed with a brother
      (incest avoidance prevents sibling mating). Male prairie voles showed no effect
      of reproductive experience but showed an unexpected effect of cohabitation
      duration regardless of mating. The sex difference in the distribution of OXA-ir
      cells, and their increased number in anterior levels of the caudal hypothalamus
      of reproductively experienced female prairie voles, may reflect a sex-specific
      mechanism involved in pairbonding, parenting, or lactation in this species. 

PMID- 24874709
TI  - Orexin A-induced anxiety-like behavior is mediated through GABA-ergic, alpha- and
      beta-adrenergic neurotransmissions in mice.
AB  - Orexins are hypothalamic neuropeptides, which are involved in several
      physiological functions of the central nervous system, including anxiety and
      stress. Several studies provide biochemical and behavioral evidence about the
      anxiogenic action of orexin A. However, we have little evidence about the
      underlying neuromodulation. Therefore, the aim of the present study was to
      investigate the involvement of neurotransmitters in the orexin A-induced anxiety
      like behavior in elevated plus maze (EPM) test in mice. Accordingly, mice were
      pretreated with a non-selective muscarinic cholinergic antagonist, atropine; a
      gamma-aminobutyric acid subunit A (GABA-A) receptor antagonist, bicuculline; a
      D2, D3, D4 dopamine receptor antagonist, haloperidol; a non-specific nitric oxide
      synthase (NOS) inhibitor, nitro-l-arginine; a nonselective alpha-adrenergic
      receptor antagonist, phenoxybenzamine and a beta-adrenergic receptor antagonist,
      propranolol 30min prior to the intracerebroventricular administration of orexin
      A. The EPM test started 30min after the i.c.v. injection of the neuropeptide. Our
      results show that orexin A decreases significantly the time spent in the arms
      (open/open+closed) and this action is reversed by bicuculline, phenoxybenzamine
      and propranolol, but not by atropine, haloperidol or nitro-l-arginine. Our
      results provide evidence for the first time that the orexin A-induced anxiety
      like behavior is mediated through GABA-A-ergic, alpha- and beta-adrenergic
      neurotransmissions, whereas muscarinic cholinergic, dopaminergic and nitrergic
      neurotransmissions may not be implicated. 

PMID- 24874710
TI  - Enthalpy-driven nuclease-like activity and mechanism of peptide-chlorambucil
      conjugates.
AB  - We report the results of attaching the anticancer drug chlorambucil (CLB) to two
      high-affinity DNA binding peptides: Met-Hyp-Arg-Lys-(Py)4-Lys-Arg-NH2 (HyM-10)
      and Gln-Hyp-Arg-Lys-(Py)4-Lys-Arg-NH2 (HyQ-10). These CLB-peptide conjugates
      cleave DNA very effectively and sequence-selectively without the use of
      chemicals, heat, or UV irradiation. Polyacrylamide gel electrophoresis identifies
      the sites where CLB-HyM-10 and CLB-HyQ-10 attack a complementary pair of 5'-(32)P
      labeled duplexes derived from pBR322 in the absence of piperidine or other
      chemical additives. Matrix-assisted laser desorption ionization time-of-flight
      mass spectrometry (MALDI-TOF-MS) has confirmed the preferential cleavage sites as
      well as a novel stepwise cleavage mechanism of sequence-selective DNA cleavage.
      Resembling restriction endonucleases, the CLB-peptide conjugates appear to be
      capable of producing double strand DNA breaks. Circular dichroism studies show
      that CLB-HyM-10 and CLB-HyQ-10 induce significant local conformational changes in
      DNA via the minor groove, possibly with dimeric binding stoichiometry. The
      energetic basis of DNA binding by these conjugates has been investigated by
      isothermal titration calorimetry, revealing that the binding of both the peptides
      and their CLB conjugates is overwhelmingly enthalpy-driven. The maintenance of a
      conserved negative binding free energy in DNA-conjugate interactions is a crucial
      feature of the universal enthalpy-entropy compensation phenomenon. The strongly
      enthalpy-driven binding of CLB-peptide conjugates to preferred loci in DNA
      furnishes the required proximity effect to generate the observed nuclease-like
      sequence-selective cleavage. 

PMID- 24874711
TI  - Synchronization of masseter activity patterns between the right and left sides
      during chewing in healthy young males.
AB  - Masseter activity patterns during chewing, which were quantitatively assessed
      using T50 values, were compared between the right and left sides of healthy young
      males. Surface electromyograms were recorded from both masseters, and each
      participant was asked to chew four different agar samples at his own pace across
      two separate sessions. The four agar samples, each possessing differing textural
      properties, consisted of two normal and two distinctive agar varieties. The
      Pearson's correlation coefficient was calculated for each pair of T50 values to
      evaluate the degree of synchronization of activity patterns between both
      masseters. A three-way analysis of variance revealed significant main effects of
      the 'participant' and 'experimental session' factors, but not of the 'test food'.
      The number of significant coefficients increased stepwise by increasing the
      number of chews per sequence. These results suggest the importance of the initial
      stages of chewing sequences in facilitating the synchronization of bilateral
      masseter activity patterns.

PMID- 24874712
TI  - Covalently anchored carboxyphenyl monolayer via aryldiazonium ion grafting: a
      well-defined reactive tether layer for on-surface chemistry.
AB  - Electrografting of aryl films to electrode surfaces from diazonium ion solutions
      is a widely used method for preparation of modified electrodes. In the absence of
      deliberate measures to limit film growth, the usual film structure is a loosely
      packed multilayer. For some applications, monolayer films are advantageous; our
      interest is in preparing well-defined monolayers of reactive tethers for further
      on-surface chemistry. Here, we describe the synthesis of an aryl diazonium salt
      with a protected carboxylic acid substituent. After electrografting to glassy
      carbon electrodes and subsequent deprotection, the layer is reacted with amine
      derivatives. Electrochemistry and atomic force microscopy are used to monitor the
      grafting, deprotection, and subsequent coupling steps. Attempts to follow the
      same procedures on gold surfaces suggest that the grafted layer is not stable in
      these reaction conditions. 

PMID- 24874715
TI  - Eu@COK-16, a host sensitized, hybrid luminescent metal-organic framework.
AB  - A new concept of luminescent host-guest materials was developed by introduction
      of Eu(3+) into COK-16, a HKUST-1 type hybrid metal-organic framework (MOF) with
      cation exchange properties. In Eu@COK-16, the luminescent ion resides in the pore
      system of the MOF. The luminescence properties of Eu@COK-16 have been studied
      based on excitation and emission, allowing analysis of intramolecular energy
      transfer processes from the COK-16 host to the exchanged Eu(3+) ions. Both the
      framework trimesate (BTC) and encapsulated [PW12O40](3-) ions contribute to
      energy transfer. Since the antenna molecules (BTC) are part of the framework
      structure and [PW12O40](3-) ions only partly occupy one of the three types of
      cavities in the structure, a large fraction of the pore volume in this host
      sensitized luminescent MOF remains available for catalysis applications or
      adsorption of additional sensitizing molecules. The material structure was
      determined from a combination of elemental analysis, XAS, XRD, electron and
      luminescence spectroscopy. 

PMID- 24874713
TI  - Estimating endogenous dopamine levels at D2 and D3 receptors in humans using the
      agonist radiotracer [(11)C]-(+)-PHNO.
AB  - Using positron emission tomography (PET) and an acute dopamine depletion
      challenge it is possible to estimate endogenous dopamine levels occupying
      dopamine D2/3 receptors (D2/3R) in humans in vivo. Our group has developed
      [(11)C]-(+)-PHNO, the first agonist radiotracer with preferential in vivo
      affinity for D3R. Thus, the use of [(11)C]-(+)-PHNO offers the novel possibility
      of (i) estimating in vivo endogenous dopamine levels at D2/3R using an agonist
      radiotracer, and (ii) estimating endogenous dopamine levels at D3R in
      extrastriatal regions such as the substantia nigra, hypothalamus, and ventral
      pallidum. Ten healthy participants underwent a [(11)C]-(+)-PHNO PET scan under
      baseline conditions and another under acute endogenous dopamine depletion
      achieved via oral administration of alpha-methyl-para-tyrosine (64 mg/kg).
      [(11)C]-(+)-PHNO binding was sensitive to acute dopamine depletion, allowing in
      vivo estimates of endogenous dopamine in D2R-rich regions (caudate and putamen),
      mixed D2/3R-rich regions (ventral striatum and globus pallidus), and
      extrastriatal D3R-rich regions (hypothalamus and ventral pallidum). Dopamine
      depletion decreased self-reported vigor, which was correlated with the reduction
      in dopamine levels in the globus pallidus. [(11)C]-(+)-PHNO is a suitable
      radiotracer for use in estimating endogenous dopamine levels at D2R and D3R in
      neuropsychiatric populations. 

PMID- 24874716
TI  - DFT study on the mechanisms and diastereoselectivities of Lewis acid-promoted
      ketene-alkene [2 + 2] cycloadditions: what is the role of Lewis acid in the
      ketene and C = X (X = O, CH2, and NH) [2 + 2] cycloaddition reactions?
AB  - The detailed mechanisms and diastereoselectivities of Lewis acid-promoted ketene
      alkene [2 + 2] cycloaddition reactions have been studied by density functional
      theory (DFT). Four possible reaction channels, including two noncatalyzed
      diastereomeric reaction channels (channels A and B) and two Lewis acid (LA)
      ethylaluminum dichloride (EtAlCl2) catalyzed diastereomeric reaction channels
      (channels C and D), have been investigated in this work. The calculated results
      indicate that channel A (associated with product R-configurational cycloputanone)
      is more energy favorable than channel B (associated with the other product S
      configurational cyclobutanone) under noncatalyzed condition, but channel D
      leading to S-configurational cyclobutanone is more energy-favorable than channel
      C, leading to R-configurational cycloputanone under a LA-promoted condition,
      which is consistent with the experimental results. And Lewis acid can make the
      energy barrier of ketene-alkene [2 + 2] cycloaddition much lower. In order to
      explore the role of LA in ketene and C = X (X = O, CH2, and NH) [2 + 2]
      cycloadditions, we have tracked and compared the interaction modes of frontier
      molecular orbitals (FMOs) along the intrinsic reaction coordinate (IRC) under the
      two different conditions. Besides by reducing the energy gap between the FMOs of
      the reactants, our computational results demonstrate that Lewis acid lowers the
      energy barrier of the ketene and C = X [2 + 2] cycloadditions by changing the
      overlap modes of the FMOs, which is remarkably different from the traditional FMO
      theory. Furthermore, analysis of global reactivity indexes has also been
      performed to explain the role of LA catalyst in the ketene-alkene [2 + 2]
      cycloaddition reaction. 

PMID- 24874714
TI  - Distinct mu, delta, and kappa opioid receptor mechanisms underlie low sociability
      and depressive-like behaviors during heroin abstinence.
AB  - Addiction is a chronic disorder involving recurring intoxication, withdrawal, and
      craving episodes. Escaping this vicious cycle requires maintenance of abstinence
      for extended periods of time and is a true challenge for addicted individuals.
      The emergence of depressive symptoms, including social withdrawal, is considered
      a main cause for relapse, but underlying mechanisms are poorly understood. Here
      we establish a mouse model of protracted abstinence to heroin, a major abused
      opiate, where both emotional and working memory deficits unfold. We show that
      delta and kappa opioid receptor (DOR and KOR, respectively) knockout mice develop
      either stronger or reduced emotional disruption during heroin abstinence,
      establishing DOR and KOR activities as protective and vulnerability factors,
      respectively, that regulate the severity of abstinence. Further, we found that
      chronic treatment with the antidepressant drug fluoxetine prevents emergence of
      low sociability, with no impact on the working memory deficit, implicating
      serotonergic mechanisms predominantly in emotional aspects of abstinence
      symptoms. Finally, targeting the main serotonergic brain structure, we show that
      gene knockout of mu opioid receptors (MORs) in the dorsal raphe nucleus (DRN)
      before heroin exposure abolishes the development of social withdrawal. This is
      the first result demonstrating that intermittent chronic MOR activation at the
      level of DRN represents an essential mechanism contributing to low sociability
      during protracted heroin abstinence. Altogether, our findings reveal crucial and
      distinct roles for all three opioid receptors in the development of emotional
      alterations that follow a history of heroin exposure and open the way towards
      understanding opioid system-mediated serotonin homeostasis in heroin abuse. 

PMID- 24874721
TI  - Spinal infections due to Eikenella corrodens: case report and literature review.
AB  - Spinal infections with Eikenella corrodens are rare. We report a unique case of
      infection caused by E. corrodens diagnosed more than two years after cervical
      surgery. All other published cases of spinal infections caused by E. corrodens
      were searched. Characteristics of this bacterium, its challenging diagnosis and
      therapy are discussed.

PMID- 24874717
TI  - Vimentin regulates neuroplasticity in transected spinal cord rats associated with
      micRNA138.
AB  - Spinal cord injury (SCI) often results in motor disability concomitant with limit
      neuroplasticity; the underlying mechanism, however, is still unclear. This study
      established spinal cord transection rats model (T10), then performed cDNA
      microarray analysis and found that vimentin located in astrocytes was increased
      significantly in scar tissues after transection. To understand the role of
      vimentin and it's mechanism of regulation, RNA interference and luciferase assay
      were used. Vimentin knockdown in the scar tissues showed a significant
      improvement on locomotor function in hindlimbs, while vimentin overexpression
      exhibited an opposite effect. In vitro, vimentin downregulation or overexpression
      can effectively inhibit or increase astrogliosis, respectively. Moreover, by
      using biological informatics technology, we predicted that vimentin may be as the
      target of micRNA138 (miR-138), and confirmed that miR-138 could regulate vimentin
      by luciferase activity assay. The present results not only validated the exact
      role of vimentin in transected spinal cord, but also exhibited a novel regulation
      mechanism, in which miR-138 may regulate vimentin to promote neuroplasticity. It,
      therefore, provides a novel target for gene drug discovery based on miRNA-138 or
      vimentin for the treatment of SCI in the future clinic trial.

PMID- 24874722
TI  - Role of radiosurgery in the management of pineal region tumours: indications,
      method, outcome.
AB  - Numerous tumour types can occur in the pineal region. Because these tumours are
      uncommon and heterogeneous, it is often difficult to establish optimal treatment
      strategies based on comparative clinical trials. To date, the role of
      radiosurgery for the treatment of pineal region tumours remains controversial.
      This report of a 10-year single-department experience and review of the
      literature focuses on the spectrum of pathologic features found in these pineal
      parenchymal tumours and on the interest of radiosurgery in their management.
      Considering pineocytomas, although these tumours have been considered to be
      radioresistant to fractionated radiotherapy, our results are in agreement with
      similar results reported in the literature in suggesting that radiosurgery may be
      an alternative to surgical resection or an adjuvant therapy when the resection is
      not optimal. When dissemination occurs after radiosurgery, however, craniospinal
      radiation and chemotherapy are necessary. Radiosurgery has also proven its
      interest in the treatment of germinomas as an alternative to encephalic
      radiotherapy with limited long-term damage. Regarding the other pathologies,
      radiosurgery can be considered as part of a multimodal treatment including
      surgery, chemo-radiotherapy and its role still has to be clearly defined. 

PMID- 24874723
TI  - Gold-catalyzed cascade cyclization of (azido)ynamides: an efficient strategy for
      the construction of indoloquinolines.
AB  - (Azido)ynamides were efficiently converted into indoloquinolines by the use of a
      gold catalyst. While ynamides bearing an allylsilane gave terminal alkenes,
      ynamides bearing a simple alkene gave cyclopropanes. This reaction proceeds
      through the formation of an alpha-amidino gold carbenoid. 

PMID- 24874724
TI  - Cosmeceutical effect on skin surface profiles and epidermis in UV-B-irradiated
      mice.
AB  - IMPORTANCE: These data may be useful for developing guidelines for clinicians and
      the general population related to the reversal of photoaging effects on the aging
      face damaged by solar radiation. OBJECTIVE: To investigate antiaging effects of 4
      commercially available topical agents on the dorsal skin in photoaged hairless
      mice. DESIGN AND SETTING: Animal study at an academic medical center. Animals
      comprised 56 female Skh-1 hairless mice (6-8 weeks old). Skin samples were
      collected from nonirradiated intact mice (control), mice irradiated with UV-B for
      8 weeks, mice irradiated with UV-B and then exposed to a topical cosmeceutical
      applied for 5 weeks, and UV-B-irradiated mice not exposed to cosmeceuticals and
      retained for 5 weeks until the end of the experiment. INTERVENTION: The mice were
      exposed to UV-B light 3 times a week for 2 months, followed by topical
      application of a peptide, antioxidant, estrogen, and retinoic acid agent for 5
      weeks. MAIN OUTCOMES AND MEASURES: Surface features such as wrinkling were
      analyzed from replicas along with histomorphometric determination of epidermal
      thickness, sebocyte counts, and immunohistochemical study of proliferating cell
      nuclear antigen (PCNA). RESULTS: Exposure to UV-B induced significant wrinkle
      formation after 13 weeks, which was attenuated with treatments with a peptide
      cream, antioxidant mixture, and estrogen cream (mean [SD] Rz values: control [C],
      60.7 [19.0]; irradiated [RAD], 51.8 [15.9] [P < .001]; irradiated-long [RAD
      long], 86.0 [28.3] [P = .01]; antioxidant [AO], 45.2 [13.2]; peptide, 63.4
      [18.8], estrogen, 64.6 [21.2]; retinoic acid [RA], 73.9 [28.5]; RAD-long vs C [P
      = .01], vs RAD [P < .001], vs estrogen [P = .04], vs peptide [P = .02], vs AO
      [P<.001], vs RA [P = .25]. There was a trend of reversal of irradiation-induced
      augmentation of epidermal thickness in animals treated with the peptide and AO
      (mean [SD] epidermal width: C, 21.0 [2.2] MUm; RAD, 41.3 [7.0] MUm [P < .001];
      RAD-long, 39.1 [11.0] MUm [P = .006]; AO, 37.3 [14] MUm [P < .001]; peptide, 33.9
      [3.8] MUm [P = .01]; estrogen, 59.2 [9.2] MUm [P = .003]; RA, 52.4 [8.7] MUm [P <
      .001]). Retinoic acid augmented epidermal width and sebocyte counts (mean [SD]
      sebocyte data [number per gland]: C, 9.4 [2.0]; RAD, 11.69 [1.5] [P < .001]; RAD
      long, 6.5 [1.3] [P = .73]; peptide, 7.2 [1.7] [P = .03]; estrogen, 4.1 [0.9] [P <
      .001]; AO, 7.2 [1.7] [P = .06]; RA, 11.0 [1.4] [P = .01]). Estrogen cream was
      effective in restoring surface features but enhanced thickness of epidermis in
      irradiated specimens. All groups had a higher PCNA index score except for peptide
      treatment, which brought it down to the control level (mean [SD] PCNA index
      values: C, 17.3 [1.5]; RAD, 32.4 [6.8] [P < .001]; RAD-long, 34.0 [6.1] [P <
      .001]; AO, 62.1 [3.5] [P = .01]; peptide, 20.1 [6.3] [P < .001]; estrogen, 56.8
      [10.0] [P < .001]; RA, 35.2 [10.2] [P < .001]). CONCLUSIONS AND RELEVANCE: Of the
      4 cosmeceuticals tested within this experimental period, peptide cream and
      antioxidant mixture were the most effective overall in reversing photoaging
      effects; retinoic acid was the least effective of these topical agents. LEVEL OF
      EVIDENCE: NA.

PMID- 24874725
TI  - Depressive symptoms, lifestyle structure, and ART adherence among HIV-infected
      individuals: a longitudinal mediation analysis.
AB  - Despite the well-documented relationship between depression and antiretroviral
      therapy (ART) nonadherence, few studies have identified explanatory pathways
      through which depression affects adherence. The current study tested lifestyle
      structure-the degree of organization and routinization of daily activities-as a
      mediator of this relationship, given previous evidence of lifestyle structure
      being associated with both depression and ART nonadherence. HIV-infected
      individuals starting or re-starting ART in the California Collaborative Treatment
      Group 578 study (n = 199) were assessed over 48 weeks. Adherence was measured
      using electronic monitoring caps to determine dose timing and doses taken, and
      viral load was assessed. The mediating role of lifestyle structure was tested
      using generalized linear mixed-effects modeling and bootstrapping. Lifestyle
      significantly mediated the relationship between depression and both measures of
      ART adherence behavior. Interventions that minimize disruptions to lifestyle
      structure and link adherence to daily activities may be useful for individuals
      with depression and ART nonadherence.

PMID- 24874726
TI  - Surgical treatment of stage IA2 cervical cancer.
AB  - BACKGROUND: Cervical cancer is the second most common cancer among women up to 65
      years of age and is the most frequent cause of death from gynaecological cancers
      worldwide. Women with International Federation of Gynecology and Obstetrics
      (FIGO) stage IA2 cervical cancer have measured stromal invasion (when the cancer
      breaks through the basement membrane of the epithelium) of greater than 3 mm and
      no greater than 5 mm in depth with a horizontal surface extension of no more than
      7 mm. For stage IA2 disease, radical hysterectomy with pelvic lymphadenectomy or
      radiotherapy is the standard treatment. In order to avoid complications of more
      radical surgical methods, less invasive options, such as simple hysterectomy,
      simple trachelectomy or conisation, with or without pelvic lymphadenectomy, may
      be feasible for stage IA2 disease, considering the relative low risk of local or
      distant metastatic disease. The evidence for less radical tumour excision and for
      the role of systematic lymphadenectomy in stage IA2 cervical cancer is not clear.
      OBJECTIVES: To evaluate the effectiveness and safety of less radical surgery in
      stage IA2 cervical cancer. SEARCH METHODS: We searched the Cochrane
      Gynaecological Cancer Group trials register, Cochrane Central Register of
      Controlled Trials (CENTRAL), MEDLINE and EMBASE up to September 2013. We also
      searched registers of clinical trials and abstracts of scientific meetings.
      SELECTION CRITERIA: We searched for randomised controlled trials (RCTs) that
      compared surgical techniques in women with stage IA2 cervical cancer. DATA
      COLLECTION AND ANALYSIS: Two review authors independently assessed whether
      potentially relevant studies met the inclusion criteria. We found no trials and,
      therefore, no data were analysed. MAIN RESULTS: The search strategy identified
      982 unique references, which were all excluded on the basis of title and abstract
      because it was clear that they did not meet the inclusion criteria. We identified
      one relevant large ongoing trial, so it is anticipated that we will be able to
      add this evidence to this review in the future. AUTHORS' CONCLUSIONS: We found no
      evidence to inform decisions about different surgical techniques in women with
      stage IA2 cervical cancer. In the future, the results of one large ongoing RCT
      should allow comparison of different types of surgery.

PMID- 24874727
TI  - Degradation of mutant p53H175 protein by Zn(II) through autophagy.
AB  - TP53, one of the most important oncosuppressors, is frequently mutated in cancer.
      Several p53 mutant proteins escape proteolytic degradation and are highly
      expressed in an aberrant conformation often acquiring pro-oncogenic activities
      that promote tumor progression and resistance to therapy. Therefore, it has been
      vastly proposed that reactivation of wild-type (wt) function(s) from mutant p53
      (mutp53) may have therapeutic significance. We have previously reported that
      Zn(II) restores a folded conformation from mutp53 misfolding, rescuing wild-type
      (wt) p53/DNA-binding and transcription activities. However, whether Zn(II)
      affects mutp53 stability has never been investigated. Here we show that a novel
      Zn(II) compound induced mutp53 (R175H) protein degradation through autophagy, the
      proteolytic machinery specifically devoted to clearing misfolded proteins.
      Accordingly, pharmacological or genetic inhibition of autophagy prevented Zn(II)
      mediated mutp53H175 degradation as well as the ability of the Zn(II) compound to
      restore wtp53 DNA-binding and transcription activity from this mutant. By
      contrast, inhibition of the proteasome failed to do so, suggesting that autophagy
      is the main route for p53H175 degradation. Mechanistically, Zn(II) restored the
      wtp53 ability to induce the expression of the p53 target gene DRAM (damage
      regulated autophagy modulator), a key regulator of autophagy, leading to
      autophagic induction. Accordingly, inhibition of wtp53 transactivation by
      pifithrin-alpha (PFT-alpha) impaired both autophagy and mutp53H175 degradation
      induced by curcumin-based zinc compound (Zn(II)-curc). Viewed together, our
      results uncover a novel mechanism employed by Zn(II)-curc to reactivate
      mutp53H175, which involves, at least in part, induction of mutp53 degradation via
      wtp53-mediated autophagy. 

PMID- 24874728
TI  - Systems biology: a way to make complex problems more understandable.

PMID- 24874730
TI  - From computational modelling of the intrinsic apoptosis pathway to a systems
      based analysis of chemotherapy resistance: achievements, perspectives and
      challenges in systems medicine.
AB  - Our understanding of the mitochondrial or intrinsic apoptosis pathway and its
      role in chemotherapy resistance has increased significantly in recent years by a
      combination of experimental studies and mathematical modelling. This combined
      approach enhanced the quantitative and kinetic understanding of apoptosis signal
      transduction, but also provided new insights that systems-emanating functions
      (i.e., functions that cannot be attributed to individual network components but
      that are instead established by multi-component interplay) are crucial
      determinants of cell fate decisions. Among these features are molecular
      thresholds, cooperative protein functions, feedback loops and functional
      redundancies that provide systems robustness, and signalling topologies that
      allow ultrasensitivity or switch-like responses. The successful development of
      kinetic systems models that recapitulate biological signal transduction observed
      in living cells have now led to the first translational studies, which have
      exploited and validated such models in a clinical context. Bottom-up strategies
      that use pathway models in combination with higher-level modelling at the tissue,
      organ and whole body-level therefore carry great potential to eventually deliver
      a new generation of systems-based diagnostic tools that may contribute to the
      development of personalised and predictive medicine approaches. Here we review
      major achievements in the systems biology of intrinsic apoptosis signalling,
      discuss challenges for further model development, perspectives for higher-level
      integration of apoptosis models and finally discuss requirements for the
      development of systems medical solutions in the coming years. 

PMID- 24874731
TI  - Systems biology of death receptor networks: live and let die.
AB  - The extrinsic apoptotic pathway is initiated by death receptor activation. Death
      receptor activation leads to the formation of death receptor signaling platforms,
      resulting in the demolition of the cell. Despite the fact that death receptor
      mediated apoptosis has been studied to a high level of detail, its quantitative
      regulation until recently has been poorly understood. This situation has
      dramatically changed in the last years. Creation of mathematical models of death
      receptor signaling led to an enormous progress in the quantitative understanding
      of the network regulation and provided fascinating insights into the mechanisms
      of apoptosis control. In the following sections, the models of the death receptor
      signaling and their biological implications will be addressed. Central attention
      will be given to the models of CD95/Fas/APO-1, an exemplified member of the death
      receptor signaling pathways. The CD95 death-inducing signaling complex (DISC) and
      regulation of CD95 DISC activity by its key inhibitor c-FLIP, have been
      vigorously investigated by modeling approaches, and therefore will be the major
      topic here. Furthermore, the non-linear dynamics of the DISC, positive feedback
      loops and bistability as well as stoichiometric switches in extrinsic apoptosis
      will be discussed. Collectively, this review gives a comprehensive view how the
      mathematical modeling supported by quantitative experimental approaches has
      provided a new understanding of the death receptor signaling network. 

PMID- 24874732
TI  - Systems biology approaches to develop innovative strategies for lung cancer
      therapy.
AB  - Lung cancer (LC) is a number one killer of cancer-related death among men and
      women worldwide. Major advances have been made in the diagnosis, staging and use
      of surgery for LC, but systemic chemotherapy and radiotherapy alone or in
      combination with some targeted agents remains the core treatment of advanced LC.
      Unfortunately, in spite of improved diagnosis, surgical methods and new
      treatments, mortality is still extremely high among LC patients. To understand
      the precise functioning of signaling pathways associated with resistance to
      current treatments in LC, as well as to identify novel treatment regimens, a
      holistic approach to analyze signaling networks should be applied. Here, we
      describe systems biology-based approaches to generate biomarkers and novel
      therapeutic targets in LC, as well as how this may contribute to personalized
      treatment for this malignancy. 

PMID- 24874733
TI  - Cell-to-cell variability in cell death: can systems biology help us make sense of
      it all?
AB  - One of the most common observations in cell death assays is that not all cells
      die at the same time, or at the same treatment dose. Here, using the perspective
      of the systems biology of apoptosis and the context of cancer treatment, we
      discuss possible sources of this cell-to-cell variability as well as its
      implications for quantitative measurements and computational models of cell
      death. Many different factors, both within and outside of the apoptosis signaling
      networks, have been correlated with the variable responses to various death
      inducing treatments. Systems biology models offer us the opportunity to take a
      more synoptic view of the cell death process to identify multifactorial
      determinants of the cell death decision. Finally, with an eye toward 'systems
      pharmacology', we discuss how leveraging this new understanding should help us
      develop combination treatment strategies to compel cancer cells toward apoptosis
      by manipulating either the biochemical state of cancer cells or the dynamics of
      signal transduction. 

PMID- 24874734
TI  - Receptor-interacting protein kinases modulate noise-induced sensory hair cell
      death.
AB  - Receptor-interacting protein (RIP) kinases promote the induction of necrotic cell
      death pathways. Here we investigated signaling pathways in outer hair cells
      (OHCs) of adult male CBA/J mice exposed to noise that causes permanent threshold
      shifts, with a particular focus on RIP kinase-regulated necroptosis. One hour
      after noise exposure, nuclei of OHCs in the basal region of the cochlea displayed
      both apoptotic and necrotic features. RIP1 and RIP3 protein levels increased and
      caspase-8 was activated. Treatment with pan-caspase inhibitor ZVAD blocked the
      activation of caspase-8 and reduced the number of apoptotic nuclei, while
      increasing levels of RIP1, RIP3, and necrotic OHCs. Conversely, treatment with
      necrosis inhibitor necrostatin-1 (Nec-1) or RIP3 siRNA (siRIP3) diminished noise
      induced increases in RIP1 and RIP3, and decreased necrotic OHC nuclei. This
      treatment also increased the number of apoptotic nuclei without increasing
      activation of caspase-8. Consistent with the elevation of levels of RIP1 and
      RIP3, noise-induced active AMPKalpha levels increased with ZVAD treatment, but
      decreased with Nec-1 and siRIP3 treatment. Furthermore, treatment with siRIP3 did
      not alter the activation of caspase-8, but instead increased activation of
      caspase-9 and promoted endonuclease G translocation into OHC nuclei. Finally,
      auditory brainstem response functional measurements and morphological assessment
      of OHCs showed that ZVAD treatment reduces noise-induced deficits. This
      protective function is potentiated when combined with siRIP3 treatment. In
      conclusion, noise-induced OHC apoptosis and necrosis are modulated by caspases
      and RIP kinases, respectively. Inhibition of either pathway shifts the prevalence
      of OHC death to the alternative pathway. 

PMID- 24874729
TI  - Systems biology of cisplatin resistance: past, present and future.
AB  - The platinum derivative cis-diamminedichloroplatinum(II), best known as
      cisplatin, is currently employed for the clinical management of patients affected
      by testicular, ovarian, head and neck, colorectal, bladder and lung cancers. For
      a long time, the antineoplastic effects of cisplatin have been fully ascribed to
      its ability to generate unrepairable DNA lesions, hence inducing either a
      permanent proliferative arrest known as cellular senescence or the mitochondrial
      pathway of apoptosis. Accumulating evidence now suggests that the cytostatic and
      cytotoxic activity of cisplatin involves both a nuclear and a cytoplasmic
      component. Despite the unresolved issues regarding its mechanism of action, the
      administration of cisplatin is generally associated with high rates of clinical
      responses. However, in the vast majority of cases, malignant cells exposed to
      cisplatin activate a multipronged adaptive response that renders them less
      susceptible to the antiproliferative and cytotoxic effects of the drug, and
      eventually resume proliferation. Thus, a large fraction of cisplatin-treated
      patients is destined to experience therapeutic failure and tumor recurrence.
      Throughout the last four decades great efforts have been devoted to the
      characterization of the molecular mechanisms whereby neoplastic cells
      progressively lose their sensitivity to cisplatin. The advent of high-content and
      high-throughput screening technologies has accelerated the discovery of cell
      intrinsic and cell-extrinsic pathways that may be targeted to prevent or reverse
      cisplatin resistance in cancer patients. Still, the multifactorial and redundant
      nature of this phenomenon poses a significant barrier against the identification
      of effective chemosensitization strategies. Here, we discuss recent systems
      biology studies aimed at deconvoluting the complex circuitries that underpin
      cisplatin resistance, and how their findings might drive the development of
      rational approaches to tackle this clinically relevant problem. 

PMID- 24874735
TI  - Elf3 drives beta-catenin transactivation and associates with poor prognosis in
      colorectal cancer.
AB  - Aberrant regulation of the Wnt/beta-catenin pathway plays important roles in
      colorectal carcinogenesis, with over 90% of cases of sporadic colon cancer
      featuring beta-catenin accumulation. While ubiquitination-mediated degradation is
      widely accepted as a major route for beta-catenin protein turnover, little is
      known about the regulation of beta-catenin in transcriptional level. Here we show
      that Elf3, a member of the E-twenty-six family of transcription factors, drives
      beta-catenin transactivation and associates with poor survival of colorectal
      cancer (CRC) patients. We first found recurrent amplification and upregulation of
      Elf3 in CRC tissues, and further Gene Set Enrichment Analysis identified
      significant association between Elf3 expression and activity of WNT/beta-catenin
      pathway. Chromatin immunoprecipitation and electrophoretic mobility shift assay
      consistently revealed that Elf3 binds to and transactivates beta-catenin
      promoter. Ectopic expression of Elf3 induces accumulation of beta-catenin in both
      nucleus and cytoplasm, causing subsequent upregulation of several effector genes
      including c-Myc, VEGF, CCND1, MMP-7 and c-Jun. Suppressing Elf3 in CRC cells
      attenuates beta-catenin signaling and decreases cell proliferation, migration and
      survival. Targeting Elf3 in xenograft tumors suppressed tumor progression in
      vivo. Taken together, our data identify Elf3 as a pivotal driver for beta-catenin
      signaling in CRC, and highlight potential prognostic and therapeutic significance
      of Elf3 in CRC. 

PMID- 24874736
TI  - Serum-dependent processing of late apoptotic cells for enhanced efferocytosis.
AB  - Binding of the serum protein complement component C1q to the surface of dying
      cells facilitates their clearance by phagocytes in a process termed
      efferocytosis. Here, we investigate during which phase of apoptotic cell death
      progression C1q binding takes place. Purified C1q was found to bind to all dying
      cells and, albeit weaker, also to viable cells. The presence of serum abrogated
      completely the binding to viable cells. In addition, C1q binding to dying cells
      was limited to a specific subpopulation of late apoptotic/secondary necrotic
      cells. Co-culturing serum-treated apoptotic cells with human monocytes revealed a
      much higher phagocytosis of C1q-positive than of C1q-negative late
      apoptotic/secondary necrotic cells. But this phagocytosis-promoting activity
      could not be observed with purified C1q. Serum-treated C1q-positive late
      apoptotic/secondary necrotic cells exhibited a similar volume, a similar degraded
      protein composition, but a much lower DNA content in comparison with the
      remaining late apoptotic/secondary necrotic cells. This was mediated by a serum
      bound nuclease activity that could be abrogated by G-actin, which is a specific
      inhibitor of serum DNase I. These results show that serum factors are involved in
      the prevention of C1q binding to viable cells and in the processing of late
      apoptotic/secondary necrotic cells promoting cell death progression toward
      apoptotic bodies. This process leads to the exposure of C1q-binding structures
      and facilitates efferocytosis. 

PMID- 24874737
TI  - Role of alpha-synuclein in autophagy modulation of primary human T lymphocytes.
AB  - It has been demonstrated that alpha-synuclein can aggregate and contribute to the
      pathogenesis of some neurodegenerative diseases and it is capable of hindering
      autophagy in neuronal cells. Here, we investigated the implication of alpha
      synuclein in the autophagy process in primary human T lymphocytes. We provide
      evidence that: (i) knocking down of the alpha-synuclein gene resulted in
      increased autophagy, (ii) autophagy induction by energy deprivation was
      associated with a significant decrease of alpha-synuclein levels, (iii) autophagy
      inhibition by 3-methyladenine or by ATG5 knocking down led to a significant
      increase of alpha-synuclein levels, and (iv) autophagy impairment, constitutive
      in T lymphocytes from patients with systemic lupus erythematosus, was associated
      with abnormal accumulation of alpha-synuclein aggregates. These results suggest
      that alpha-synuclein could be considered as an autophagy-related marker of
      peripheral blood lymphocytes, potentially suitable for use in the clinical
      practice. 

PMID- 24874739
TI  - Macropinocytosis and TAK1 mediate anti-inflammatory to pro-inflammatory
      macrophage differentiation by HIV-1 Nef.
AB  - Macrophages (MPhi) are functionally classified into two types, anti-inflammatory
      M2 and pro-inflammatory M1. Importantly, we recently revealed that soluble HIV-1
      proteins, particularly the pathogenetic protein Nef, preferentially activate M2
      MPhi and drive them towards an M1-like MPhi, which might explain the sustained
      immune activation seen in HIV-1-infected patients. Here, we show that the
      preferential effect of Nef on M2-MPhi is mediated by TAK1 (TGF-beta-activated
      kinase 1) and macropinocytosis. As with MAP kinases and NF-kappaB pathway, Nef
      markedly activated TAK1 in M-CSF-derived M2-MPhi but not in GM-CSF-derived M1
      MPhi. Two Nef mutants, which were unable to activate MAP kinases and NF-kappaB
      pathway, failed to activate TAK1. Indeed, the TAK1 inhibitor 5Z-7-oxozeaenol as
      well as the ectopic expression of a dominant-negative mutant of TAK1 or TRAF2, an
      upstream molecule of TAK1, inhibited Nef-induced signaling activation and M1-like
      phenotypic differentiation of M2-MPhi. Meanwhile, the preferential effect of Nef
      on M2-MPhi correlated with the fact the Nef entered M2-MPhi more efficiently than
      M1-MPhi. Importantly, the macropinosome formation inhibitor EIPA completely
      blocked the internalization of Nef into M2-MPhi. Because the macropinocytosis
      activity of M2-MPhi was higher than that of M1-MPhi, our findings indicate that
      Nef enters M2-MPhi efficiently by exploiting their higher macropinocytosis
      activity and drives them towards M1-like MPhi by activating TAK1. 

PMID- 24874738
TI  - Bioactive lipids and the control of Bax pro-apoptotic activity.
AB  - Lipids are key regulators of cell physiology through the control of many aspects
      of cellular life and survival. In particular, lipids have been implicated at
      different levels and through many different mechanisms in the cell death program
      called apoptosis. Here, we discuss the action of lipids in the regulation of the
      activation and the integration of Bax into the mitochondrial outer membrane, a
      key pro-apoptotic member of the BCL-2 family. We describe how, during apoptosis,
      lipids can act simultaneously or in parallel as receptors or ligands for Bax to
      stimulate or inhibit its pro-death activity. 

PMID- 24874741
TI  - Mammalian STE20-like kinase 2, not kinase 1, mediates photoreceptor cell death
      during retinal detachment.
AB  - Photoreceptor cell death is the definitive cause of vision loss in retinal
      detachment (RD). Mammalian STE20-like kinase (MST) is a master regulator of both
      cell death and proliferation and a critical factor in development and
      tumorigenesis. However, to date the role of MST in neurodegeneration has not been
      fully explored. Utilizing MST1(-/-) and MST2(-/-) mice we identified MST2, but
      not MST1, as a regulator of photoreceptor cell death in a mouse model of RD.
      MST2(-/-) mice demonstrated significantly decreased photoreceptor cell death and
      outer nuclear layer (ONL) thinning after RD. Additionally, caspase-3 activation
      was attenuated in MST2(-/-) mice compared to control mice after RD. The
      transcription of p53 upregulated modulator of apoptosis (PUMA) and Fas was also
      reduced in MST2(-/-) mice post-RD. Retinas of MST2(-/-) mice displayed suppressed
      nuclear relocalization of phosphorylated YAP after RD. Consistent with the
      reduction of photoreceptor cell death, MST2(-/-) mice showed decreased levels of
      proinflammatory cytokines such as monocyte chemoattractant protein 1 and
      interleukin 6 as well as attenuated inflammatory CD11b cell infiltration during
      the early phase of RD. These results identify MST2, not MST1, as a critical
      regulator of caspase-mediated photoreceptor cell death in the detached retina and
      indicate its potential as a future neuroprotection target. 

PMID- 24874740
TI  - The cockayne syndrome B protein is essential for neuronal differentiation and
      neuritogenesis.
AB  - Cockayne syndrome (CS) is a progressive developmental and neurodegenerative
      disorder resulting in premature death at childhood and cells derived from CS
      patients display DNA repair and transcriptional defects. CS is caused by
      mutations in csa and csb genes, and patients with csb mutation are more
      prevalent. A hallmark feature of CSB patients is neurodegeneration but the
      precise molecular cause for this defect remains enigmatic. Further, it is not
      clear whether the neurodegenerative condition is due to loss of CSB-mediated
      functions in adult neurogenesis. In this study, we examined the role of CSB in
      neurogenesis by using the human neural progenitor cells that have self-renewal
      and differentiation capabilities. In this model system, stable CSB knockdown
      dramatically reduced the differentiation potential of human neural progenitor
      cells revealing a key role for CSB in neurogenesis. Neurite outgrowth, a
      characteristic feature of differentiated neurons, was also greatly abolished in
      CSB-suppressed cells. In corroboration with this, expression of MAP2 (microtubule
      associated protein 2), a crucial player in neuritogenesis, was also impaired in
      CSB-suppressed cells. Consistent with reduced MAP2 expression in CSB-depleted
      neural cells, tandem affinity purification and chromatin immunoprecipitation
      studies revealed a potential role for CSB in the assembly of transcription
      complex on MAP2 promoter. Altogether, our data led us to conclude that CSB has a
      crucial role in coordinated regulation of transcription and chromatin remodeling
      activities that are required during neurogenesis. 

PMID- 24874742
TI  - Involvement of p38 in signal switching from autophagy to apoptosis via the
      PERK/eIF2alpha/ATF4 axis in selenite-treated NB4 cells.
AB  - Selenite has emerged as an optional chemotherapeutic agent for hematological
      malignancies. Autophagy and apoptosis are both engaged in selenite-induced cell
      death. In a previous report, we have identified heat shock protein 90 (Hsp90) as
      a critical modulator of the balance between autophagy and apoptosis in selenite
      treated leukemia cells. However, the mechanisms by which selenite mediates the
      crosstalk between autophagy and apoptosis remain largely unknown. Herein, we
      demonstrate that the endoplasmic reticulum (ER) stress-related
      PERK/eIF2alpha/ATF4 pathway and p38 are core modules for the selenite-induced
      switch to apoptosis from autophagy. We found that selenite activated PERK and
      eIF2alpha/ATF4 downstream to promote apoptosis. During this progression, p38 was
      dissociated from PERK-inhibiting Hsp90 and became autophosphorylated. Then,
      activated p38 further enhanced the docking of activating transcription factor 4
      (ATF4) onto the CHOP (CCAAT/enhancer-binding protein homologous protein) promoter
      via eIF2alpha to enhance apoptosis. We also found that activated p38 suppressed
      the phosphorylation of eIF4E that directed ATF4 to bind to the MAP1LC3B
      (microtubule-associated protein 1 light chain 3B) promoter. Because of the
      deactivation of eIF4E, the association of ATF4 with the MAP1LC3B promoter was
      inhibited, and autophagy was compromised. Intriguingly, p53 played important
      roles in mediating the p38-mediated regulation of eIF2alpha and eIF4E. When
      activated by p38, p53 induced the phosphorylation of eIF2alpha and the
      dephosphorylation of eIF4E, particularly in the nucleus where the ATF4
      transcription factor was modulated, ultimately resulting in differential
      expression of CHOP and LC3. Moreover, selenite exhibited potent antitumor effects
      in vivo. In an NB4 cell xenograft model, selenite induced apoptosis and hampered
      autophagy. In addition, related signaling proteins demonstrated similar changes
      to those observed in vitro. These data suggest that selenite may be a candidate
      drug for leukemia therapy. 

PMID- 24874744
TI  - Graphical user interface for yield and dose estimations for cyclotron-produced
      technetium.
AB  - The cyclotron-based (100)Mo(p,2n)(99m)Tc reaction has been proposed as an
      alternative method for solving the shortage of (99m)Tc. With this production
      method, however, even if highly enriched molybdenum is used, various radioactive
      and stable isotopes will be produced simultaneously with (99m)Tc. In order to
      optimize reaction parameters and estimate potential patient doses from
      radiotracers labeled with cyclotron produced (99m)Tc, the yields for all reaction
      products must be estimated. Such calculations, however, are extremely complex and
      time consuming. Therefore, the objective of this study was to design a graphical
      user interface (GUI) that would automate these calculations, facilitate analysis
      of the experimental data, and predict dosimetry. The resulting GUI, named
      Cyclotron production Yields and Dosimetry (CYD), is based on Matlab(r). It has
      three parts providing (a) reaction yield calculations, (b) predictions of gamma
      emissions and (c) dosimetry estimations. The paper presents the outline of the
      GUI, lists the parameters that must be provided by the user, discusses the
      details of calculations and provides examples of the results. Our initial
      experience shows that the proposed GUI allows the user to very efficiently
      calculate the yields of reaction products and analyze gamma spectroscopy data.
      However, it is expected that the main advantage of this GUI will be at the later
      clinical stage when entering reaction parameters will allow the user to predict
      production yields and estimate radiation doses to patients for each particular
      cyclotron run. 

PMID- 24874743
TI  - CREAM: a database for chemotherapy resistance-associated miRSNP.

PMID- 24874745
TI  - The tyrosine kinase inhibitor dasatinib effectively blocks PDGF-induced orbital
      fibroblast activation.
AB  - BACKGROUND: Graves' ophthalmopathy (GO) remains hard to treat. Excessive orbital
      fibroblast activation by platelet-derived growth factor (PDGF)-BB contributes to
      GO. The tyrosine kinase inhibitors (TKIs) imatinib mesylate and dasatinib both
      target PDGF-receptor tyrosine kinase activity, albeit with a different potency.
      We compared the efficacy of these TKIs on PDGF-BB-induced proliferation, and on
      cytokine and hyaluronan production by orbital fibroblasts. Also the capacity of
      dasatinib to suppress GO-associated gene expression in orbital tissue was
      examined. METHODS: Orbital fibroblasts from four GO patients and five control
      subjects were used. The efficacy of the two TKIs was tested by: 1) pre-incubating
      orbital fibroblasts overnight with different TKI concentrations, followed by 24 h
      stimulation with PDGF-BB, 2) adding TKI and PDGF-BB simultaneously to the orbital
      fibroblasts in 24 h cultures. Proliferation was assessed by colorimetric assay.
      Hyaluronan and cytokine production were measured by ELISA. Furthermore, orbital
      tissue was obtained from a patient with active GO, and the effect of dasatinib on
      the expression levels of HAS2-, CCL2-, IL6-, and IL8-mRNA expression was examined
      by real-time quantitative PCR. RESULTS: Pre-incubation of orbital fibroblasts
      with imatinib mesylate or dasatinib resulted in significant and dose-dependent
      inhibition of PDGF-BB-induced orbital fibroblast proliferation, and hyaluronan
      and cytokine production. Dasatinib exhibited these effects at far lower
      concentrations. The same results were observed in the setting where TKI and PDGF
      BB treatments were commenced simultaneously. In orbital tissue from active GO,
      dasatinib significantly suppressed HAS2-, CCL2-, IL6- and IL8-mRNA levels.
      CONCLUSION: Dasatinib may be a promising alternative to high-dose steroids in the
      treatment of GO.

PMID- 24874747
TI  - Corneal nerve alterations in different stages of Fuchs' endothelial corneal
      dystrophy: an in vivo confocal microscopy study.
AB  - PURPOSE: To analyze potential alterations in corneal nerve morphology and
      function in different stages of Fuchs' endothelial corneal dystrophy (FECD).
      METHODS: Thirty eyes with FECD underwent in vivo confocal microscopy using the
      Heidelberg Retina Tomograph II (HRT II; Heidelberg Engineering, Heidelberg,
      Germany) and the Rostock Cornea Module (RCM) to quantify the morphology of the
      central subbasal corneal nerve plexus (total nerve length, total nerve number,
      number of main nerve trunks, number of nerve branches) as well as esthesiometry
      (using the Cochet-Bonnet esthesiometer) of the central cornea to determine
      central corneal sensation as a measure of nerve function. Findings were
      correlated with an age-matched control group of 30 healthy individuals.
      Comparisons to biomicroscopical stage of FECD, visual acuity and central corneal
      thickness were performed using Spearman correlation. RESULTS: Depending on slit
      lamp examination, all 30 eyes were classified into FECD stage 1-4 (stage 1: six
      eyes; stage 2: 15 eyes; stage 3: six eyes; stage 4: three eyes). Total nerve
      length (rho = -0.8, p < 0.001), total nerve number (rho = -0.7, p < 0.001),
      number of main nerve trunks (rho = -0.6, p < 0.001), and number of nerve branches
      (rho = -0.7, p < 0.001) decreased significantly with increasing FECD stages.
      Comparing to the visual acuity, significant positive correlations were found for
      total nerve length (rho = 0.5, p = 0.012), total nerve number (rho = 0.5, p =
      0.005), number of main nerve trunks (rho = 0.4, p = 0.017), and number of nerve
      branches (rho = 0.5, p = 0.009). With central corneal thickness, there were
      significant inverse correlations for total nerve length (rho = -0.6, p = 0.001),
      total nerve number (rho = -0.5, p = 0.012), number of main nerve trunks (rho = 
      0.4, p = 0.015), and number of nerve branches (rho = -0.4, p = 0.017). Central
      corneal sensation was full in all FECD stage 1, stage 2 and stage 3 eyes, but
      mildly reduced in FECD stage 4 eyes. CONCLUSIONS: Increasing severity of Fuchs'
      endothelial corneal dystrophy (FECD) is concurrent with marked attenuation of the
      density, as well as mild diminishment of the function, of the subbasal corneal
      nerve plexus in late stage of the disease.

PMID- 24874749
TI  - Alerations in the development of the main olfactory bulb of the mouse after
      ethanol exposure.
AB  - The effect of ethanol on the development of the main olfactory bulb (OB) was
      examined by light and electron microscopy in 21-day-old Swiss mice (CD-1),
      exposed to ethanol from embryonic day 13 to postnatal day 21. Two control groups
      were included in the study to rule out changes due to malnourishment: a normal
      control group, whose dams were fed rodent lab chow throughout the study and a
      pairfed group, whose dams were fed the same amount of liquid diet as the dams in
      the ethanol group but with sucrose replacement of ethanol. Somatic growth,
      measured by length and body weight, was retarded to the same degree in ethanol
      and pairfed mice, indicating a similar level of malnourishment in both groups
      without an additional ethanol effect. The most striking change in olfactory bulb
      development was the stunted growth of this structure in the ethanol-exposed
      animals with reductions in the volume of the glomerular. external plexiform and
      granular cell layers. The laminar organization and cellular cytoarchitecture were
      not substantially altered by ethanol or malnourishment except for a retarded
      migration of the periglomerular cells in the ethanol-treated group. Examination
      of synaptogenesis in the external plexiform layer (EPL) of olfactory bulb from 21
      day-old mice in the three groups revealed no treatment-related changes in
      synaptic structure, appositional length or ratios of the two dominant type of EPL
      synapses, which are formed between dendrites of the output neurons (mitral and
      tufted cells) and granule cells. However, morphometric analysis revealed elevated
      densities of both synaptic types in the ethanol-exposed group but with no change
      in the total synaptic number per olfactory bulb. The results suggest that ethanol
      exposure of mice after the latter half of gestation and during the postnatal
      period primarily affects the growth of the olfactory bulb probably by decreasing
      neuronal cell growth, and/or proliferation but has little affect on other aspects
      of maturation such as formation of cortical structure, differentiation and
      synaptogenesis. 

PMID- 24874750
TI  - Long term reduction in eight arm maze performance after early exposure to
      phenobarbital.
AB  - Performance in the hippocampal eight arm maze was studied in mice after early
      exposure to phenobarbital (PhB). since previous studies suggested that these
      animals suffered neural deficits in the hippocampus. For prenatal exposure
      pregnant mothers were fed 3 g PhB/kg milled food on gestation days 9-18. Neonates
      were injected daily with 50 mg PhB/kg. on postnatal days 2-21. After a week of
      water deprivation, the animals were tested at age 50 days for 5 days preceded by
      1 day of habituation. Deficits in eight arm maze performance were demonstrated in
      early treated mice on every testing day. For example, on day 5 of testing the
      number of correct entries during the first eight attempts in the prenatally
      treated group were 12% below control level (P<0.01), the respective reduction in
      the neonatal group was 10% (P< 0.001). The number of trials needed to enter all
      arms on day 5 was 27% above control level among prenatally treated mice (P<
      0.001), and 13% in neonatally treated mice (P< 0.05). It took prenatal PhB
      animals twice the time to reach criterion than their controls (P< 0.001) and four
      times as long for neonatally treated mice (P< 0.001). 

PMID- 24874748
TI  - Enzymatic etching of gold nanorods by horseradish peroxidase and application to
      blood glucose detection.
AB  - Gold nanorods (AuNRs) have become some of the most used nanostructures for
      biosensing and imaging applications due to their plasmon-related optical
      response, which is highly sensitive toward minute changes in the AuNR aspect
      ratio. In this context, H2O2 has been used to trigger the chemical etching of
      AuNRs, thereby inducing a decrease of their aspect ratio. However, special
      conditions and relatively high concentrations of H2O2 are usually required,
      preventing the applicability of the system for biodetection purposes. To overcome
      this limitation we have introduced a biocatalytic species, the enzyme horseradish
      peroxidase (HRP) that is able to induce a gradual oxidation of AuNRs in the
      presence of trace concentrations of H2O2. Interestingly, the presence of halide
      ions has also been found to be essential for this process. As a consequence,
      other enzymatic reactions, such as those catalyzed by glucose oxidase, can be
      easily coupled to HRP activity, allowing the detection of different amounts of
      glucose. On the basis of these findings, we developed a highly sensitive and
      simple colorimetric assay that can be read out by the naked eye and allows the
      detection of physiological glucose concentrations in human serum. 

PMID- 24874751
TI  - Neurogenesis of the magnocellular basal telencephalic nuclei in the rat.
AB  - Neurogenesis in the magnocellular basal telencephalic nuclei of the rat was
      examined with [(3)H]thymidine autoradiography. The experimental animals were the
      offspring of pregnant females given two injections of [(3)H]thymidine on
      consecutive embryonic (E) days (E12-E13, E13-E14, ... E21-E22). On postnatal day
      (P) 60, the percentage of labeled cells and the proportion of cells originating
      during 24 h periods were quantified at several anatomical levels throughout the
      magnocellular basal telencephalic nuclei. The neurons of the horizontal limb of
      the diagonal band originate mainly between E13 and E16 in a combined rostral-to
      caudal and lateral-to-medial gradient. The neurogenetic gradients in the
      horizontal limb are continued by generation patterns of cells in the vertical
      limb of the diagonal band-medial septal complex, the large cells in the polymorph
      layer of the olfactory tubercle, and the large cells of the anterior amygdaloid
      area. The substantia innominata originates between E13 and E17 in combined caudal
      to-rostral and lateral-to-medial gradients. The globus pallidus originates
      between E13 and E17 in combined caudal-to-rostral, ventral-to-dorsal and medial
      to-lateral gradients. The entopeduncular nucleus originates between E12 and E14
      in a 'sandwich' gradient where neurons in the core of the nucleus are older than
      those in either the anterior or posterior ends. There is an overall superficial
      (ventral) to deep (dorsal) neurogenetic gradient between the magnocellular basal
      nuclei present at any given rostrocaudal level. An important finding is that
      neurogenetic gradients in the individual components of the magnocellular basal
      nuclei are alike (with the possible exception of the entopeduncular nucleus)
      indicating they are part of a single system. Finally, evidence is presented that
      neurogenetic gradients in the magnocellular basal telencephalic neurons can be
      correlated with their anatomical projections to the cerebral cortex. 

PMID- 24874746
TI  - Two-year visual outcome of polypoidal choroidal vasculopathy treated with
      photodynamic therapy combined with intravitreal injections of ranibizumab.
AB  - PURPOSE: To investigate the 2-year outcomes of photodynamic therapy (PDT)
      combined with intravitreal injections of ranibizumab for polypoidal choroidal
      vasculopathy (PCV). METHODS: Ninety-five eyes with subfoveal PCV treated with
      combined therapy were followed for >=24 months. The association between visual
      outcomes and single nucleotide polymorphisms in ARMS2 A69S and CFH I62V genes
      were examined without adjusting for multiple comparisons. RESULTS: Visual acuity
      (VA) improvement was observed at month 3 (P = 0.009). The improvement persisted
      until month 12 (P = 0.003), when VA began the decline back to baseline values at
      month 24. To investigate the factors associated with VA reduction during the
      second year, patients were divided into those with and those without a second
      year VA reduction. Both patients with and without a second-year VA reduction
      showed similar VA changes over the first year. The first-year VA improvement was
      not predictive of the VA decline over the second year. Genetic analyses showed no
      significant difference in the frequency of the A risk allele of CFH I62V between
      patients with and without a second-year VA reduction. However, patients with the
      T risk allele of A69S had a higher rate of recurrence and were more likely to
      experience a reduction in VA during the second year when compared to patients
      without (P = 0.020 and P = 0.048, respectively). CONCLUSIONS: PDT combined
      therapy resulted in significant visual recovery in the first year, which was not
      sustained during the second year. VA reduction in the second year was affected by
      genetic factors.

PMID- 24874752
TI  - Postnatal development of rat cerebellum: Glycosaminoglycan changes related to
      variation in water content, cell formation and organ growth.
AB  - Modifications of glycosaminoglycans were studied during rat cerebellum
      ontogenesis. Levels of both hyaluronic acid and sulphated glycosaminoglycans
      increase during development but not at the same rate as cerebellar size or
      proteins. As in the rest of the brain, cerebellar hyaluronic acid concentration
      decreases during development but not, as expected, in parallel with the loss of
      tissue water content. In contrast to forebrain, the concentration of cerebellar
      sulphated glycosaminoglycans decreases at a slow rate. The correlation, suggested
      by several authors, between glycosaminoglycans concentration and tissue
      hydratation, cell migration and myelination were not confirmed in developing rat
      cerebellum. 

PMID- 24874753
TI  - Receptor-mediated uptake of labeled transferrin by embryonic chicken dorsal root
      ganglion neurons in culture.
AB  - Transferrin is a growth-promoting plasma protein which is known to occur within
      developing neurons. Since little information exists on the process by which
      transferrin is internalized by neurons, we studied this process using dissociated
      embryonic chicken dorsal root ganglion neurons in culture. Cultured dorsal root
      ganglion neurons were incubated in the presence of 3.75 nM (125)I-transferrin at
      37 degrees C, the cultures were extensively washed, the neurons were solubilized
      in a Triton-containing buffer and internalized (125)I-transferrin was quantified
      with a gamma counter. (125)I-transferrin was internalized in a linear fashion for
      at least 60 min, and this uptake was abolished by the presence of 1.25 MUM
      unlabeled transferrin. No competition for the uptake of (125)I-transferrin was
      observed in the presence of 1.25 MUM ovalbumin, cytochrome c, hemoglobin,
      insulin, horseradish peroxidase, aldolase or the carboxyl-terminal fragment
      ('half-site') of transferrin. By contrast, uptake was inhibited by approximately
      50% in the presence of the ammo-terminal fragment ('half-site') of transferrin
      (1.25 MUM) or in the presence of concanavalin A (1.25 MUM). The binding of
      transferrin conjugated to fluorescein isothiocyanate to neurons at 4 degrees C
      and its subsequent internalization at 37 degrees C was demonstrated by
      fluorescence microscopy of unfixed cells following incubation of the neurons in
      the presence of the fluorescently labeled protein. Furthermore, the transferrin
      receptors were visualized immunocytochemically on the surface membranes of dorsal
      root ganglion neurons using rabbit antibodies directed against transferrin
      receptors from chicken reticulocytes. From these data, we conclude that
      transferrin is internalized by neurons via receptor-mediated endocytosis, and
      suggest that this protein may serve an important role in the development and
      survival of dorsal root ganglion neurons. 

PMID- 24874754
TI  - Substance P-like immunoreactivity in developing cranial parasympathetic neurons
      of the rat.
AB  - Substance P-like immunoreactivity (SPLI) has been observed in cell bodies of
      fetal cranial parasympathetic ganglia of rat. It first appears at day 16 of
      gestation at the same time as in cranial sensory ganglia. From day 17 to 21, SPLI
      neurons constitute most, if not all, submandibular-sublingual and intralingual
      ganglia, they form 30-40% of otic and pterygopalatine ganglia and numerous such
      neurons are found in the myenteric plexus of the esophagus as well as in
      pharyngeal and buccal walls. The immunoreactive material is thinly granular, and
      its appearance does not change with prenatal development. The immunoreactivity in
      cell bodies of parasympathetic ganglia decreases at the end of the gestational
      period, and cannot be evidenced any more in most cells of normal adult ganglia.
      However, the corresponding SPLI fibers remain intensely immunoreactive. When
      grafted to rat irides, which have been chemically depleted of intrinsic SPLI
      fibers, submandibular, otic and pterygopalatine ganglia from pre- or postnatal
      rats rapidly produce a large amount of SPLI fibers on the iris mimicking the
      pattern of sensory innervation. This proves the presence of SPLI neurons in adult
      parasympathetic ganglia, at least in experimental conditions. This study of
      fetuses and grafts demonstrates the existence of neurons in SPLI parasympathetic
      cranial ganglia which has been underestimated or ignored previously as a result
      of observations on adult ganglia. The very large proportion of SPLI neurons in
      the ganglia of the salivary gland might be of importance for the interpretation
      of experimental studies on the control of salivation. The presence of SPLI in all
      three types of peripheral ganglia, sensory, sympathetic and parasympathetic,
      raises the question of its functional significance in the different compartments
      of the peripheral nervous system. 

PMID- 24874755
TI  - The effects of apomorphine and isoproterenol on the 'transport response' in the
      white rat.
AB  - In a series of four experiments, the ability of specific catecholaminergic
      agonists to intensify the 'transport response' was investigated in 19-, 32-, 36-
      and 40-day-old rats. The dopaminergic agonist, apomorphine, was able to intensify
      the response in a dose-dependent fashion. The beta-noradrenergic agonist,
      isoproterenol, was unable to alter the intensity of the response. These results
      indicate a central dopaminergic involvement in the transport response. 

PMID- 24874756
TI  - Serotoninergic receptors in the visual system of light-deprived rats.
AB  - The level of binding of [(3)H]serotonin (5-hydroxytryptamine) to serotonin type 1
      receptors (S1) in the visual centres and frontal cortex of control, dark reared
      and monocularly deprived (one eyelid sutured on postnatal day 10) 3-month-old
      rats were determined and compared to that assayed in 25-day-old rats. The two
      forms of light deprivation affect [(3)H]serotonin binding in the central visual
      structures in a different way. Monocular deprivation until the age of 3 months
      resulted in decreased serotonin binding levels in the retina of both eyes
      compared to the control group raised under a 12 h light-dark cycle. Additionally,
      serotonin binding in the lateral geniculate nucleus contralateral to the closed
      eye is decreased. Rearing rats in complete darkness from birth to the age of 3
      months leads to an increase of serotonin binding in the visual cortex and
      superior colliculus. Regarding the normal distribution of serotonin type 1
      binding sites in the visual system of 3-month-old rats, highest serotonin binding
      is found in the lateral geniculate nucleus followed by the retina, superior
      colliculus and visual cortex. The differential effect of monocular or total light
      deprivation upon serotonin type 1 receptors in the different visual nuclei might
      reflect differences in the morpho-functional organization of the serotoninergic
      system along the visual pathway and its involvement in visual information
      processing. 

PMID- 24874757
TI  - Timecourse of effects of triiodothyronine on mouse cerebellar cells cultured by
      two different methods.
AB  - Dissociated cells from week-old mouse cerebellum were grown on either polylysine
      coated coverslips or on uncoated coverslips. Polylysine coated coverslips give
      rise to cultures containing all of the cerebellar cell types except Purkinje
      cells. Use of uncoated coverslips gives rise to cultures which are depleted of
      granule cells because the granule cells are unable to adhere to glass without a
      substrate present. The uncoated coverslip cultures are therefore enriched in
      glial and other non-neuronal cells. Effects of triiodothyronine on each type of
      culture were then examined as a function of time. On coated coverslips hormone
      treatment caused a noticeable increase in cell clumping at 1 week, and seemed
      responsible for a leveling off of the decline in total high-affinity uptake of
      gamma-aminobutyric acid, as well as for a small increase in beta-alanine
      inhibited uptake between 2 and 3 weeks. There was no effect on the overall uptake
      of thymidine. On uncoated coverslips triiodothyronine treatment significantly
      increased the thymidine uptake at days 2 and 3, and increased the proportion of
      Bergmann-like to velate astrocytes at 1 week. There were, however, no significant
      differences in GABA uptake at any of the time points examined. We conclude that
      in cerebellar cultures lacking Purkinje cells, triiodothyronine affects both the
      rate of acquisition and the timecourse of morphological changes (possibly
      reflecting transformation to more differentiated states) of glial cells but not
      of neurons. These results are consistent with the hypothesis that, in vivo,
      thyroxine acts indirectly via Purkinje cells to give developmental signals to
      neuroblasts and/ or neurons. 

PMID- 24874758
TI  - Extracellular matrix glycoprotein (hyaluronectin) in early cerebral development
      Immunofluorescence study of the rat embryo.
AB  - The distribution of hyaluronectin, an extracellular matrix glycoprotein binding
      specifically to hyaluronate, was studied by indirect immunofluorescence in the
      cerebral cortex of the rat embryo. On days 11 and 12 thin strands of
      immunofluorescent material spanning the entire thickness of the telencephalon
      were seen. The appearance was similar to that observed with vimentin antisera
      decorating radial glia. On days 13-15 the primordial plexiform layer of the
      cerebral cortex was intensely hyaluronectin positive. On day 16 hyaluronectin
      immunoreactivity was mainly confined to Layer I above and to the intermediate
      layer below the newly formed cortical plate. It is suggested that in embryonal
      rat brain HN immunoreactivity is first distributed along radial glia and then
      accumulates in regions of axonal growth and neuropil formation. 

PMID- 24874759
TI  - A systematic review of community opioid overdose prevention and naloxone
      distribution programs.
AB  - Community-based opioid overdose prevention programs (OOPPs) that include the
      distribution of naloxone have increased in response to alarmingly high overdose
      rates in recent years. This systematic review describes the current state of the
      literature on OOPPs, with particular focus on the effectiveness of these
      programs. We used systematic search criteria to identify relevant articles, which
      we abstracted and assigned a quality assessment score. Nineteen articles
      evaluating OOPPs met the search criteria for this systematic review. Principal
      findings included participant demographics, the number of naloxone
      administrations, percentage of survival in overdose victims receiving naloxone,
      post-naloxone administration outcome measures, OOPP characteristics, changes in
      knowledge pertaining to overdose responses, and barriers to naloxone
      administration during overdose responses. The current evidence from nonrandomized
      studies suggests that bystanders (mostly opioid users) can and will use naloxone
      to reverse opioid overdoses when properly trained, and that this training can be
      done successfully through OOPPs. 

PMID- 24874760
TI  - Development and implementation of an opioid overdose prevention program within a
      preexisting substance use disorders treatment center.
AB  - This case study of the development and implementation of an opioid overdose
      prevention program is based on an actual clinic's experience, but information
      about the clinic, including details of implementation and outcome measures, has
      been changed. Four experts reflect on the medical, administrative, peer-support,
      community, and evaluation aspects of this case. This discussion highlights
      challenges and important considerations in the creation of programs to address
      the ever-increasing risk for opioid overdose. 

PMID- 24874761
TI  - Access to alcohol in hand sanitizer in a substance abuse treatment program: a
      potentially overlooked risk.

PMID- 24874762
TI  - Another chance to reformulate racemic methadone.

PMID- 24874764
TI  - Magnetic assembly-mediated enhancement of differentiation of mouse bone marrow
      cells cultured on magnetic colloidal assemblies.
AB  - Here we reported an interesting phenomenon that the field-induced assemblies of
      magnetic nanoparticles can promote the differentiation of primary mouse bone
      marrow cells into osteoblasts. The reason was thought to lie in the remnant
      magnetic interaction inside the assemblies which resulted from the magnetic field
      directed assembly. Influence of the assemblies on the cells was realized by means
      of interface effect rather than the internalization effect. We fabricated a
      stripe-like assemblies array on the glass plate and cultured cells on this
      surface. We characterized the morphology of assemblies and measured the mechanic
      property as well as the magnetic property. The cellular differentiation was
      measured by staining and quantitative PCR. Finally, Fe uptake was excluded as the
      reason to cause the phenomenon. 

PMID- 24874765
TI  - De novo protein sequencing by combining top-down and bottom-up tandem mass
      spectra.
AB  - There are two approaches for de novo protein sequencing: Edman degradation and
      mass spectrometry (MS). Existing MS-based methods characterize a novel protein by
      assembling tandem mass spectra of overlapping peptides generated from multiple
      proteolytic digestions of the protein. Because each tandem mass spectrum covers
      only a short peptide of the target protein, the key to high coverage protein
      sequencing is to find spectral pairs from overlapping peptides in order to
      assemble tandem mass spectra to long ones. However, overlapping regions of
      peptides may be too short to be confidently identified. High-resolution mass
      spectrometers have become accessible to many laboratories. These mass
      spectrometers are capable of analyzing molecules of large mass values, boosting
      the development of top-down MS. Top-down tandem mass spectra cover whole
      proteins. However, top-down tandem mass spectra, even combined, rarely provide
      full ion fragmentation coverage of a protein. We propose an algorithm, TBNovo,
      for de novo protein sequencing by combining top-down and bottom-up MS. In TBNovo,
      a top-down tandem mass spectrum is utilized as a scaffold, and bottom-up tandem
      mass spectra are aligned to the scaffold to increase sequence coverage.
      Experiments on data sets of two proteins showed that TBNovo achieved high
      sequence coverage and high sequence accuracy. 

PMID- 24874766
TI  - Photon counting spectral CT component analysis of coronary artery atherosclerotic
      plaque samples.
AB  - OBJECTIVE: To evaluate the capabilities of photon counting spectral CT to
      differentiate components of coronary atherosclerotic plaque based on differences
      in spectral attenuation and iodine-based contrast agent concentration. METHODS:
      10 calcified and 13 lipid-rich non-calcified histologically demonstrated
      atheromatous plaques from post-mortem human coronary arteries were scanned with a
      photon counting spectral CT scanner. Individual photons were counted and
      classified in one of six energy bins from 25 to 70 keV. Based on a maximum
      likelihood approach, maps of photoelectric absorption (PA), Compton scattering
      (CS) and iodine concentration (IC) were reconstructed. Intensity measurements
      were performed on each map in the vessel wall, the surrounding perivascular fat
      and the lipid-rich and the calcified plaques. PA and CS values are expressed
      relative to pure water values. A comparison between these different elements was
      performed using Kruskal-Wallis tests with pairwise post hoc Mann-Whitney U-tests
      and Sidak p-value adjustments. RESULTS: RESULTS for vessel wall, surrounding
      perivascular fat and lipid-rich and calcified plaques were, respectively, 1.19 +/
      0.09, 0.73 +/- 0.05, 1.08 +/- 0.14 and 17.79 +/- 6.70 for PA; 0.96 +/- 0.02,
      0.83 +/- 0.02, 0.91 +/- 0.03 and 2.53 +/- 0.63 for CS; and 83.3 +/- 10.1, 37.6 +/
      8.1, 55.2 +/- 14.0 and 4.9 +/- 20.0 mmol l(-1) for IC, with a significant
      difference between all tissues for PA, CS and IC (p < 0.012). CONCLUSION: This
      study demonstrates the capability of energy-sensitive photon counting spectral CT
      to differentiate between calcifications and iodine-infused regions of human
      coronary artery atherosclerotic plaque samples by analysing differences in
      spectral attenuation and iodine-based contrast agent concentration. ADVANCES IN
      KNOWLEDGE: Photon counting spectral CT is a promising technique to identify
      plaque components by analysing differences in iodine-based contrast agent
      concentration, photoelectric attenuation and Compton scattering.

PMID- 24874767
TI  - Detectability of simulated interstitial pneumonia on chest radiographs:
      comparison between irradiation side sampling indirect flat-panel detector and
      computed radiography.
AB  - OBJECTIVE: To compare the detectability of simulated interstitial pneumonia on
      chest radiographs between an irradiation side sampling indirect flat-panel
      detector (ISS-FPD) and computed radiography (CR). METHODS: Simulated interstitial
      pneumonia findings (ground-glass opacity, reticular opacity and honeycomb lung)
      were superimposed on an anthropomorphic chest phantom. Chest radiographs were
      acquired under three exposure levels (4.0, 3.2 and 2.0 mAs) with an ISS-FPD and
      with CR. 5 thoracic radiologists evaluated 72 images for the presence or absence
      of a lesion over each of 6 areas. A total of 1296 observations were analysed in a
      receiver-operating characteristic analysis. A jackknife method was used for the
      statistical analysis. RESULTS: The areas under the curves (AUCs) for the
      detection of simulated honeycomb lung obtained with the ISS-FPD were
      significantly larger than those obtained with CR at all exposure conditions. For
      the detection of simulated ground-glass opacity and reticular opacity, there were
      no significant differences between the two systems. In addition, the AUCs for the
      detectability of simulated honeycomb lung obtained with the ISS-FPD at all
      exposure levels were significantly larger than those obtained with CR at 4 mAs.
      CONCLUSION: The ISS-FPD was superior to CR for the detection of simulated
      honeycomb lung. Provided that the chosen model is representative of interstitial
      pneumonia, the use of an ISS-FPD might reduce a patient's exposure dose during
      the detection of interstitial pneumonia. ADVANCES IN KNOWLEDGE: The ISS-FPD has
      shown its advantage compared with CR in the detection of honeycombing, one sign
      of interstitial pneumonia.

PMID- 24874768
TI  - Corneal ray tracing versus simulated keratometry for estimating corneal power
      changes after excimer laser surgery.
AB  - PURPOSE: To evaluate whether the refractive changes induced by excimer laser
      surgery can be accurately measured by corneal ray tracing performed by a combined
      rotating Scheimpflug camera-Placido-disk corneal topographer (Sirius). SETTING:
      Private practices. DESIGN: Evaluation of diagnostic test. METHODS: This
      multicenter retrospective study comprised patients who had myopic or hyperopic
      excimer laser refractive surgery. Preoperatively and postoperatively, 2 corneal
      power measurements--simulated keratometry (K) and mean pupil power--were
      obtained. The mean pupil power was the corneal power calculated over the entrance
      pupil by ray tracing through the anterior and posterior corneal surfaces using
      Snell's law. Agreement between the refractive and corneal power change was
      analyzed according to Bland and Altman. Regression analysis and Bland-Altman
      plots were used to evaluate agreement between measurements. RESULTS: The study
      evaluated 72 eyes (54 patients). The difference between the postoperative and
      preoperative simulated K values underestimated the refractive change after myopic
      correction and overestimated it after hyperopic correction. Agreement between
      simulated K changes and refractive changes was poor, especially for higher
      amounts of correction. A proportional bias was detected (r = -0.77; P<.0001), and
      the 95% limits of agreement (LoA) were -0.15 -0.14 * +/-0.62 diopters (D). The
      difference between the postoperative and preoperative mean pupil power showed an
      excellent correlation with the refractive change (r(2) = 0.98). The mean pupil
      power did not overestimate or underestimate the refractive change. The 95% LoA
      ranged between -0.97 D and +0.56 D. CONCLUSION: Corneal ray tracing accurately
      measured corneal power changes after excimer laser refractive surgery. FINANCIAL
      DISCLOSURES: Dr. Calossi is consultant to Costruzione Strumenti Oftalmici. Dr.
      Carones is consultant to Wavelight Laser Technologie AG. No other author has a
      financial or proprietary interest in any material or method mentioned.

PMID- 24874769
TI  - Influence on visual function of forward light scattering associated with
      subsurface nanoglistenings in intraocular lenses.
AB  - PURPOSE: To quantitatively assess the impact of subsurface nanoglistenings on
      forward light scattering and visual function. SETTING: University of Tsukuba,
      Tsukuba, Japan. DESIGN: Case-control study. METHODS: Eyes with subsurface
      nanoglistenings and increased intraocular lens (IOL) surface light scattering and
      control eyes without subsurface nanoglistenings were evaluated. Forward light
      scattering was assessed with a double-pass device (Optical Quality Analysis
      System II) using the objective scatter index (OSI) as a quantitative parameter.
      Backward light scattering in the IOL surface was evaluated using Scheimpflug
      imaging (EAS-1000). The contrast sensitivity function was assessed as the area
      under the log contrast sensitivity function (AULCSF) measured with the Optec 6500
      device. Correlations between the OSI, visual function, age, time after surgery,
      IOL power, and backward light scattering were analyzed. RESULTS: In the study
      group, logMAR corrected distance visual acuity (CDVA) ranged from -0.176 to 0.045
      (-0.06 +/- 0.07 [SD]); no patient had a CDVA worse than 20/25. The OSI was
      significantly higher than in the control group (P=.0074) and correlated with CDVA
      (P=.0021), AULCSF photopic without glare (P=.0002) and with glare (P<.0001), and
      AULCSF mesopic without glare (P=.0038) and with glare (P=.0008). Multivariate
      analysis showed OSI was the only variable that correlated with CDVA and contrast
      sensitivity with glare. The OSI and age correlated with contrast sensitivity
      without glare (P<.05). CONCLUSIONS: Eyes with subsurface nanoglistenings had
      increased forward light scattering but no deterioration in CDVA. Increases in
      forward light scattering correlated with reductions in visual acuity and contrast
      sensitivity, although both remained within their normal range. FINANCIAL
      DISCLOSURES: No author has a financial or proprietary interest in any material or
      method mentioned.

PMID- 24874770
TI  - Femtosecond laser-assisted hyperopic laser in situ keratomileusis with tissue
      saving ablation: analysis of 800 eyes.
AB  - PURPOSE: To evaluate the results and complications of hyperopic laser in situ
      keratomileusis (LASIK) with a low-energy femtosecond laser and non-custom tissue
      saving ablation profile. SETTING: Private practice, Siena, Italy. DESIGN: Case
      series. METHODS: Hyperopic eyes with a spherical equivalent (SE) between +1.0 and
      +6.5 diopters (D) had LASIK. The flap (nominal thickness 110 MUm) was created
      with a Ziemer LDV Z2 femtosecond laser and the refractive ablation performed with
      a Technolas 217P excimer laser in tissue-saving mode. RESULTS: Eight hundred eyes
      of 413 patients were treated. The mean preoperative values were SE, +3.41 D +/-
      1.16 (SD); defocus equivalent, 4.20 +/- 1.33; corrected distance visual acuity
      (CDVA), 0.07 +/- 0.08 logMAR. At 9 months, the mean SE was -0.06 +/- 0.26 D and
      the mean defocus equivalent 0.68 +/- 0.62 (both P<.05). The defocus equivalent
      was 0.50 D or less in 594 eyes (74.3%) and 1.00 D or less in 707 eyes (88.4%).
      The mean CDVA was 0.07 +/- 0.06 logMAR; 3 eyes (0.4%) lost 2 lines of CDVA and 58
      eyes (7.3%) lost 1 line. The mean uncorrected distance visual acuity was 0.16 +/-
      0.13 logMAR. The safety index was 1.0 and the efficacy index, 0.8. The mean root
      mean-square induced primary spherical aberration was 0.65 MUm and the mean
      induced primary coma, 0.24 MUm (both P<.05). CONCLUSIONS: The low incidence of
      femtosecond-related complications was associated with good predictability,
      safety, and a low retreatment rate. The mean flap was 7 MUm thicker than
      expected. FINANCIAL DISCLOSURES: The author has no financial or proprietary
      interest in any material or method mentioned.

PMID- 24874771
TI  - Sutured posterior chamber intraocular lenses for traumatic cataract in Africa.
AB  - PURPOSE: To determine the outcomes of sutured scleral fixation of posterior
      chamber intraocular lenses (PC IOLs) after trauma in an African population.
      SETTING: State hospital and affiliated district hospital, Cape Town, South
      Africa. DESIGN: Case series. METHODS: A retrospective review was performed of the
      medical records of patients in whom a sutured PC IOL had been implanted for
      traumatic aphakia in the preceding 5 years. RESULTS: Eighty-five percent of the
      59 patients had a significant improvement in uncorrected distance visual acuity
      (UDVA) at the final visit. Two-thirds of patients achieved an UDVA of 6/18 or
      better. Those not improving had severe preexisting macular or corneal pathology.
      A significant number of patients (28%) with angle recession developed ocular
      hypertension during the postoperative period. CONCLUSION: After careful
      preoperative selection, sutured PC IOLs were effective in the visual
      rehabilitation of eyes with traumatic subluxated cataract in which the capsular
      bag could not be retained. FINANCIAL DISCLOSURE: No author has a financial or
      proprietary interest in any material or method mentioned.

PMID- 24874772
TI  - Heat shock factor HSFB2a involved in gametophyte development of Arabidopsis
      thaliana and its expression is controlled by a heat-inducible long non-coding
      antisense RNA.
AB  - Heat stress transcription factors (HSFs) are central regulators of the heat
      stress response. Plant HSFs of subgroup B lack a conserved sequence motif present
      in the transcriptional activation domain of class A-HSFs. Arabidopsis members
      were found to be involved in non-heat shock functions. In the present analysis we
      investigated the expression, regulation and function of HSFB2a. HSFB2a expression
      was counteracted by a natural long non-coding antisense RNA, asHSFB2a. In leaves,
      the antisense RNA gene is only expressed after heat stress and dependent on the
      activity of HSFA1a/HSFA1b. HSFB2a and asHSFB2a RNAs were also present in the
      absence of heat stress in the female gametophyte. Transgenic overexpression of
      HSFB2a resulted in a complete knock down of the asHSFB2a expression. Conversely,
      asHSFB2a overexpression leads to the absence of HSFB2a RNA. The knockdown of
      HSFB2a by asHSFB2a correlated with an improved, knockdown of asHSFB2a by HSFB2a
      overexpression with an impaired biomass production early in vegetative
      development. In both cases the development of female gametophytes was impaired. A
      T-DNA knock-out line did not segregate homozygous mutant plants, only
      heterozygots hsfB2a-tt1/+ were viable. Approximately 50% of the female
      gametophytes were arrested in early development, before mitosis 3, resulting in
      45% of sterile ovules. Our analysis indicates that the "Yin-Yang" regulation of
      gene expression at the HSFB2a locus influences vegetative and gametophytic
      development in Arabidopsis.

PMID- 24874773
TI  - A computationally efficient method for reconstructing sequences of MR images from
      undersampled k-space data.
AB  - In this paper, we propose a Compressive Sensing based approach to the problem of
      real-time reconstruction of MR image sequences. Our proposed method is able to
      extract useful priori information and incorporate it into a modified iterative
      thresholding algorithm for fast casual reconstruction of MR images from highly
      undersampled k-space data. Through extensive experimental results we show that
      our proposed method achieves superior reconstruction quality, while having a
      lower computational complexity and memory requirements compared to the other
      state-of-the-art methods. 

PMID- 24874775
TI  - Perinatal exposure to genistein affects the normal development of anxiety and
      aggressive behaviors and nitric oxide system in CD1 male mice.
AB  - Genistein is a phytoestrogen, particularly abundant in soybeans, that is able to
      bind estrogen receptors exerting both estrogenic and antiestrogenic activities.
      Genistein is largely present in the human diet even during pregnancy. Embryos and
      fetuses are therefore, commonly exposed to genistein during the development and
      after birth. In the present study, we used a murine model as a test end-point to
      investigate the effects of early exposure to genistein on adult male behavior and
      related neural circuits. Daily exposure of dams to genistein (100 MUg/g of body
      weight) during late pregnancy and early lactation, produced in male offspring,
      when adults, significant changes in anxiety and aggressive behaviors. Moreover,
      we found statistically significant variations in the number of neuronal nitric
      oxide synthase positive cells in the amygdala. In conclusions, these data
      indicate that early exposure to phytoestrogens may induce life-long effects on
      the differentiation of brain structures and behaviors.

PMID- 24874774
TI  - The towering orogeny of New Guinea as a trigger for arthropod megadiversity.
AB  - Early studies on Melanesian mountain systems provided insights for fundamental
      evolutionary and ecological concepts. These island-like systems are thought to
      provide opportunities in the form of newly formed, competition-free niches. Here
      we show that a hyperdiverse radiation of freshwater arthropods originated in the
      emerging central New Guinea orogen, out of Australia, about 10 million years ago.
      Further diversification was mainly allopatric, with repeated more recent
      colonization of lowlands as they emerged in the form of colliding oceanic island
      arcs, continental fragments and the Papuan Peninsula, as well as recolonization
      of the central orogen. We unveil a constant and ongoing process of lineage
      accumulation while the carrying capacity of the island is about to be reached,
      suggesting that lineage diversification speed now exceeds that of landmass/new
      ecological opportunity formation. Therefore, the central orogeny of New Guinea
      acts as a motor of diversification for the entire region. 

PMID- 24874778
TI  - A DFT study of the structures, stabilities and redox behaviour of the major
      surfaces of magnetite Fe3O4.
AB  - The renewed interest in magnetite (Fe3O4) as a major phase in different types of
      catalysts has led us to study the oxidation-reduction behaviour of its most
      prominent surfaces. We have employed computer modelling techniques based on the
      density functional theory to calculate the geometries and surface free energies
      of a number of surfaces at different compositions, including the stoichiometric
      plane, and those with a deficiency or excess of oxygen atoms. The most stable
      surfaces are the (001) and (111), leading to a cubic Fe3O4 crystal morphology
      with truncated corners under equilibrium conditions. The scanning tunnelling
      microscopy images of the different terminations of the (001) and (111)
      stoichiometric surfaces were calculated and compared with previous reports. Under
      reducing conditions, the creation of oxygen vacancies in the surface leads to the
      formation of reduced Fe species in the surface in the vicinity of the vacant
      oxygen. The (001) surface is slightly more prone to reduction than the (111), due
      to the higher stabilisation upon relaxation of the atoms around the oxygen
      vacancy, but molecular oxygen adsorbs preferentially at the (111) surface. In
      both oxidized surfaces, the oxygen atoms are located on bridge positions between
      two surface iron atoms, from which they attract electron density. The oxidised
      state is thermodynamically favourable with respect to the stoichiometric surfaces
      under ambient conditions, although not under the conditions when bulk Fe3O4 is
      thermodynamically stable with respect to Fe2O3. This finding is important in the
      interpretation of the catalytic properties of Fe3O4 due to the presence of
      oxidised species under experimental conditions. 

PMID- 24874776
TI  - Advances in the neurobiological bases for food 'liking' versus 'wanting'.
AB  - The neural basis of food sensory pleasure has become an increasingly studied
      topic in neuroscience and psychology. Progress has been aided by the discovery of
      localized brain subregions called hedonic hotspots in the early 2000s, which are
      able to causally amplify positive affective reactions to palatable tastes
      ('liking') in response to particular neurochemical or neurobiological
      stimulations. Those hedonic mechanisms are at least partly distinct from larger
      mesocorticolimbic circuitry that generates the incentive motivation to eat
      ('wanting'). In this review, we aim to describe findings on these brain hedonic
      hotspots, especially in the nucleus accumbens and ventral pallidum, and discuss
      their role in generating food pleasure and appetite. 

PMID- 24874779
TI  - Colchicine induced intraneuronal free zinc accumulation and dentate granule cell
      degeneration.
AB  - Colchicine has been discovered to inhibit many inflammatory processes such as
      gout, familial Mediterranean fever, pericarditis and Behcet disease. Other than
      these beneficial anti-inflammatory effects, colchicine blocks microtubule
      assisted axonal transport, which results in the selective loss of dentate granule
      cells of the hippocampus. The mechanism of the colchicine-induced dentate granule
      cell death and depletion of mossy fiber terminals still remains unclear. In the
      present study, we hypothesized that colchicine-induced dentate granule cell death
      may be caused by accumulation of labile intracellular zinc. 10 MUg kg(-1) of
      colchicine was injected into the adult rat hippocampus and then brain sections
      were evaluated at 1 day or 1 week later. Neuronal cell death was evaluated by H&E
      staining or Fluoro-Jade B. Zinc accumulation and vesicular zinc were detected by
      N-(6-methoxy-8-quinolyl)-para-toluene sulfonamide (TSQ) staining. To test whether
      an extracellular zinc chelator can prevent this process, CaEDTA was injected into
      the hippocampus over a 5 min period with colchicine. To test whether other
      microtubule toxins also produce similar effects as colchicine, vincristine was
      injected into the hippocampus. The present study found that colchicine injection
      induced intracellular zinc accumulation in the dentate granule cells and depleted
      vesicular zinc from mossy fiber terminals. Injection of a zinc chelator, CaEDTA,
      did not block the zinc accumulation and neuronal death. Vincristine also produced
      intracellular zinc accumulation and neuronal death. These results suggest that
      colchicine-induced dentate granule cell death is caused by blocking axonal zinc
      flow and accumulation of intracellular labile zinc. 

PMID- 24874781
TI  - Clinician-targeted intervention and patient-reported counseling on physical
      activity.
AB  - INTRODUCTION: Limited time and lack of knowledge are barriers to physical
      activity counseling in primary care. The objective of this study was to examine
      the effectiveness of a clinician-targeted intervention that used the 5As (Ask,
      Advise, Agree, Assist, Arrange) approach to physical activity counseling in a
      medically underserved patient population. METHODS: Family medicine clinicians at
      2 community health centers were randomized to Group 1 or Group 2 intervention.
      Both clinician groups participated in 4 training sessions on the 5As for physical
      activity counseling; Group 2 training took place 8 months after Group 1 training.
      Both groups were trained to refer patients to a community exercise program. We
      used a pre-post analysis to evaluate the effectiveness of the intervention on
      clinician use of 5As. Eligible patients (n = 319) rated their clinicians'
      counseling skills by using a modified Physical Activity Exit Interview (PAEI)
      survey. Clinicians (n = 10) self-assessed their use of the 5As through a survey
      and interviews. RESULTS: Both patient and clinician groups had similar
      sociodemographic characteristics. The PAEI score for both groups combined
      increased from 6.9 to 8.6 (on a scale of 0-15) from baseline to immediately
      postintervention (P = .01) and was 8.2 (P = .09) at 6-month follow-up; most of
      the improvement in PAEI score was due to increased use of 5As skills by Group 2
      clinicians. Group 1 reported difficulty with problem solving, whereas Group 2
      reported ease of referral to the community exercise program. CONCLUSION: A
      clinician training intervention showed mixed results for 5As physical activity
      counseling.

PMID- 24874782
TI  - A self-management intervention for African Americans with comorbid diabetes and
      hypertension: a pilot randomized controlled trial.
AB  - INTRODUCTION: The objective of this pilot 6-month randomized controlled trial was
      to determine the effectiveness of an intensive, community-based, group
      intervention that focused on diet, physical activity, and peer support for
      reducing weight among urban-dwelling African Americans with comorbid type 2
      diabetes and hypertension. METHODS: Sixty-one participants were randomized into
      an intervention or control group. The 6-month intervention consisted of 18 group
      sessions led by a dietitian in a community setting and weekly telephone calls
      from a peer supporter. The intervention featured culturally tailored nutrition
      education, behavioral skills training, and social support focused on changes to
      diet and physical activity. The control group consisted of two 3-hour group
      sessions of diabetes self-management education taught by a community health
      worker. Outcome measures were assessed at baseline and 6 months. The primary
      outcome was achievement of a 5% weight reduction at 6 months. A secondary outcome
      was achievement of a 0.5 percentage-point reduction in hemoglobin A1c (HbA1c).
      RESULTS: Groups did not differ in achievement of the weight-loss goal.
      Intervention participants lost a mean of 2.8 kg (P = .01); control participants
      did not lose a significant amount of weight. A greater proportion of intervention
      (50.0%) than control (21.4%) participants reduced HbA1c by 0.5 percentage points
      or more at 6 months (P = .03). CONCLUSION: The intervention was more effective
      than usual care (short-term diabetes education) at improving glycemic control,
      but not weight, in low-income African Americans with comorbid diabetes and
      hypertension. A community-based 6-month group class with culturally tailored
      education, behavioral skills training, and peer support can lead to a clinically
      significant reduction in HbA1c.

PMID- 24874784
TI  - Practice-research partnerships and mentoring to foster evidence-based decision
      making.

PMID- 24874783
TI  - Partnering with health care systems to assess tobacco treatment practices and
      beliefs among clinicians: evaluating the process.
AB  - BACKGROUND: Tobacco is a major cause of preventable illness and death. However,
      clinician use of an evidence-based guideline for treatment of tobacco use is low.
      This case study describes the process for conducting a pre-intervention
      assessment of clinician practices and beliefs regarding treatment of tobacco use.
      COMMUNITY CONTEXT: Louisiana State University Health System, one of the largest
      safety-net public hospital systems in the United States, consists of 10
      facilities in population centers across the state of Louisiana. The system serves
      a large proportion of the state's underinsured and uninsured, low-income, and
      racial/ethnic minority populations, groups that have high rates of tobacco use.
      METHODS: Activities included 1) partnering with hospital administrators to
      generate support for conducting a clinician assessment, 2) identifying and
      adapting a survey tool to assess clinicians' practices and beliefs regarding
      treatment of tobacco use, 3) developing a survey protocol and obtaining approval
      from the institutional review board, and 4) administering the survey
      electronically, using the hospital's e-mail system. OUTCOME: Existing
      partnerships and system resources aided survey administration. Use of the
      hospital's internal e-mail system and distribution of an online survey were
      effective means to engage clinicians. Following notification, 43.6% of 4,508
      clinicians opened their e-mail containing the invitation letter with a Web link
      to the survey; of these, 83.1% (1,634) completed the survey. INTERPRETATION:
      Partnering with stakeholders and using existing resources within the health care
      system are essential to successful implementation of a system-wide survey of
      clinician practices and beliefs regarding treatment of tobacco use.

PMID- 24874777
TI  - Insulin: its role in the central control of reproduction.
AB  - Insulin has long been recognized as a key regulator of energy homeostasis via its
      actions at the level of the brain, but in addition, plays a role in regulating
      neural control of reproduction. In this review, we consider and compare evidence
      from animal models demonstrating a role for insulin for physiological control of
      reproduction by effects on GnRH/LH secretion. We also review the role that
      insulin plays in prenatal programming of adult reproduction, and consider
      specific candidate neurons in the adult hypothalamus by which insulin may act to
      regulate reproductive function. Finally, we review clinical evidence of the role
      that insulin may play in adult human fertility and reproductive disorders.
      Overall, while insulin appears to have a significant impact on reproductive
      neuroendocrine function, there are many unanswered questions regarding its
      precise sites and mechanisms of action, and their impact on developing and adult
      reproductive neuroendocrine function. 

PMID- 24874785
TI  - New, potent, and selective peptidic oxytocin receptor agonists.
AB  - Mothers of preterm babies frequently have difficulty establishing or maintaining
      lactation, thought to be due to interference with the milk ejection reflex.
      Administration of exogenous oxytocin can produce alveolar contraction and
      adequate breast emptying resulting in establishment of successful lactation. The
      natural hormone oxytocin is not receptor-selective and may cause hyponatremia via
      V2 receptor mediated antidiuresis. We have designed a series of potent oxytocin
      analogues containing N-alkylglycines in position 7 with excellent selectivity
      versus the related V1a, V1b, and V2 vasopressin receptors and short half-life:
      agonists 31 ([2-ThiMeGly(7)]dOT), 47 (carba-6-[Phe(2),BuGly(7)]dOT), 55 (carba-6
      [3-MeBzlGly(7)]dOT), and 57 (carba-1-[4-FBzlGly(7)]dOT) have EC50 values at hOTR
      < 0.1 nM, selectivity ratios versus related human vasopressin receptors of >2000,
      IC50 at hV1aR > 500 nM, and total clearance in rats in the range of 60-80 mL min(
      1) kg(-1). Compound 57 (FE 202767) is currently in clinical development for the
      treatment of preterm mothers requiring lactation support.

PMID- 24874787
TI  - Gene knockout by targeted mutagenesis in a hemimetabolous insect, the two-spotted
      cricket Gryllus bimaculatus, using TALENs.
AB  - Hemimetabolous, or incompletely metamorphosing, insects are phylogenetically
      basal. These insects include many deleterious species. The cricket, Gryllus
      bimaculatus, is an emerging model for hemimetabolous insects, based on the
      success of RNA interference (RNAi)-based gene-functional analyses and transgenic
      technology. Taking advantage of genome-editing technologies in this species would
      greatly promote functional genomics studies. Genome editing using transcription
      activator-like effector nucleases (TALENs) has proven to be an effective method
      for site-specific genome manipulation in various species. TALENs are artificial
      nucleases that are capable of inducing DNA double-strand breaks into specified
      target sequences. Here, we describe a protocol for TALEN-based gene knockout in
      G. bimaculatus, including a mutant selection scheme via mutation detection
      assays, for generating homozygous knockout organisms. 

PMID- 24874788
TI  - Whole genome sequencing and the transformation of C. elegans forward genetics.
AB  - Forward genetics has been an undeniably powerful approach in Caenorhabditis
      elegans and other model organisms. However, the trek from mutant isolation to
      identification of the causative molecular lesion can be time-consuming and
      fraught with obstacles. This has changed with the advent of whole genome
      sequencing (WGS). The widespread availability of high-throughput sequencing
      technology, coupled with the increasing affordability of WGS, has enabled the
      routine use of WGS in the analysis of forward genetic screens. The noteworthy
      development of one-step mapping/sequencing approaches has largely eliminated the
      bottleneck of conventional high-resolution mapping, greatly accelerating the
      journey from mutagenesis to gene discovery. By enabling the use of increasingly
      complex and diverse genetic backgrounds as substrates for mutagenesis, WGS is
      expanding the landscape of biological problems that can be interrogated using
      forward genetic approaches in C. elegans and other organisms.

PMID- 24874786
TI  - FLP/FRT and Cre/lox recombination technology in C. elegans.
AB  - One of the most powerful aspects of biological inquiry using model organisms is
      the ability to control gene expression. A holy grail is both temporal and spatial
      control of the expression of specific gene products - that is, the ability to
      express or withhold the activity of genes or their products in specific cells at
      specific times. Ideally such a method would also regulate the precise levels of
      gene activity, and alterations would be reversible. The related goal of
      controlled or purposefully randomized expression of visible markers is also
      tremendously powerful. While not all of these feats have been accomplished in
      Caenorhabditis elegans to date, much progress has been made, and recent
      technologies put these goals within closer reach. Here, I present published
      examples of successful two-component site-specific recombination in C. elegans.
      These technologies are based on the principle of controlled intra-molecular
      excision or inversion of DNA sequences between defined sites, as driven by FLP or
      Cre recombinases. I discuss several prospects for future applications of this
      technology. 

PMID- 24874789
TI  - Facing the diagnosis of myocardial infarction: a qualitative study.
AB  - BACKGROUND: Patient experience is increasingly recognized as one of the three
      pillars of quality in health care, alongside clinical effectiveness and patient
      safety. However, little attention has been paid to the patients' experience from
      the point of view of health care delivery. OBJECTIVE: To explore the initial
      experience of patients facing a new diagnosis of myocardial infarction (MI).
      METHODS: Thirty semi-structured, individual interviews were performed. The
      Grounded Theory method was used. Atlas.ti qualitative data analysis software
      facilitated the analysis. RESULTS: Three patterns of MI diagnosis experience were
      found: a close encounter with death, severe pain, and 'silent' MI. Newly
      diagnosed MI patients who experienced a close encounter with death expected that,
      after necessary life-saving measures, their physician would not force immediate
      conversation, but leave them alone, simply to take pleasure in being alive. Newly
      diagnosed MI patients who did not experience a close encounter with death
      expected that their physician would provide not only medical care but also
      immediate emotional support and opportunities to discuss in their own words their
      ideas, thoughts, concerns and fears. Six factors facilitated patients coping with
      a new diagnosis of MI: stay in hospital, completion of diagnostic tests, trust in
      physicians, the patient's previous expectation that he/she could have a heart
      attack, the patient's personality, and the need for solitude. CONCLUSION:
      Physicians should be aware that different patterns of patient experience when
      facing MI could indicate patients' differing needs for immediate emotional
      support and communication.

PMID- 24874790
TI  - Quantification of caffeine in dietary supplements and energy drinks by solid
      surface fluorescence using a pre-concentration step on multi-walled carbon
      nanotubes and Rhodamine B.
AB  - A new method for the determination of caffeine, a non-fluorescent analyte, based
      on the enhancement of the fluorescence of Rhodamine B dye on a membrane filter
      modified with multi-walled carbon nanotubes is proposed. The method comprises pre
      concentration of caffeine on a solid support by chemofiltration in buffered
      solution onto multi-walled carbon nanotubes previously oxidised and dispersed in
      cationic surfactant admicelles. The effect of experimental parameters, including
      the nature of the buffer and pH, the nature of the solid support, filtration flow
      rate, dye and carbon nanotube concentration, and the nature of the surfactant and
      concentration were investigated by means univariation assays. Under optimum
      experimental conditions, the pre-concentration system gave detection and
      quantification limits of 0.3 and 1.1 ug l(-1), respectively. A wide linear range
      was achieved varying from concentrations of 1.1 to 9.7 * 103 ug l(-1) (r(2) =
      0.999). Satisfactory recovery values were obtained using the method of standard
      addition, confirming the feasibility of this method for caffeine determination in
      energising dietary supplements and energy drinks. 

PMID- 24874791
TI  - Drug dispersion degree and drug dissolution rate in Hybrane S1200-based instant
      release matricial particles prepared by hot melt extrusion.
AB  - The objective of this study is to evaluate the dissolution of a poorly soluble
      drug (prednisolone) from different sized matricial particles (from <250 to >1500
      um) with two drug contents (10% or 20%) obtained by hot melt extrusion using the
      hyperbranched polyesteramide Hybrane S1200 (water-soluble and with a Tg of 45 
      degrees C) as the carrier. X-ray diffraction, differential scanning calorimetry
      and SEM studies permit us to conclude that in 10% prednisolone extrudate, the
      drug is mainly dispersed within the carrier, whereas in those containing 20% an
      important fraction of the drug remains in a crystalline state and is accumulated
      on the surface of the extrudates. On particles proceeding from 10% drug
      extrudate, the drug dissolution rate is very high and slightly dependant on
      particle size and in all cases, higher than the pure micronized drug. However, on
      particles proceeding from 20% prednisolone extrudate particle size have a major
      effect on drug dissolution rate, attributable to higher proportions of
      crystalline drug accumulated on the surface, hindering polymer dissolution. Thus,
      the reduction of the particle size after extrudate grinding creates new surfaces
      from inside, that leads to strong increments on prednisolone dissolution rate,
      and becomes higher than the pure micronized drug one when the particle size is
      <250 um. 

PMID- 24874792
TI  - Optimal level of sympathectomy for primary palmar hyperhidrosis: T3 versus T4 in
      a retrospective cohort study.
AB  - BACKGROUND: To compare the results obtained with T3 versus T4 sympathectomy in
      treatment of primary palmar hyperhidrosis (PH). METHODS: By retrospective review
      of medical records of patients with PH who underwent thoracoscopic sympathectomy
      from February, 2009 to September, 2012. The patients were categorized into two
      groups: T3 group underwent T3 sympathectomy and T4 group underwent T4
      sympathectomy. Patients were evaluated according to the results of sweating,
      compensatory hyperhidrosis (CH), degree of satisfaction, complications and
      recurrence. Mean follow up was 19 +/- 7 months. RESULTS: A total of 274
      consecutive patients with PH were included in this study. There were 169 females
      and 105 males, with mean age of 29 +/- 11 years. 129 patients underwent T3
      sympathectomy (T3 group). The T4 group included 145 patients who underwent T4
      sympathectomy. 71.7% patients of T4 group did not complain of CH in comparison to
      25.6% patients in group T3 (P = 0.001) and the incidence of mild to moderate CH
      was higher in the T3 group than T4 (64.4% vs. 26.9%; p = 0.001). T4 group showed
      a great significance in the (very satisfied category) in comparison to T3 group
      (P = 0.001). The incidence of over-dry hands was significantly lower in group T4
      (0.7%, 1 out of 145) than in group T3 (8.5%, 11 out of 129). The recurrence rate
      was similar in the two groups (0.8% vs. 1.4%; P = 0.19). CONCLUSION: Video
      assisted T3 or T4 sympathectomy is a safe and effective procedure for treatment
      of palmar hyperhidrosis. T4 sympathectomy appears associated with less severe
      dryness and CH than T3 sympathectomy at long-term follow-up.

PMID- 24874793
TI  - Major sources of MeO/OH-BDEs in the East China Sea elucidated from their records
      and phytoplankton biomarkers.
AB  - Hydroxylated (OH-) and methoxylated (MeO-) polybrominated diphenyl ethers (PBDEs)
      have caused much concern because of their potential toxicity and worldwide
      distribution. These compounds are recently suggested to originate from the
      natural process in the ocean. However, their source remains highly controversial.
      In this study, we analyzed the contents of nine MeO-BDEs, ten OH-BDEs, and
      phytoplankton biomarkers (PBs) in two sediment cores collected from the East
      China Sea (ECS). The detection of 6-MeO-BDE-47, 2'-MeO-BDE-68, and 6-OH-BDE-47
      have been reported since the 1920s, prior to the production of PBDEs. Significant
      relations were found between MeO/OH-BDEs and indicators of marine organic
      matters. The similar down-core variations and significant correlations between
      MeO/OH-BDEs and PBs suggest the possibility that phytoplankton produced these
      natural compounds. Laboratory incubation further demonstrates that phytoplankton
      can produce MeO-BDEs. Comparisons between the content ratios of 6-MeO-BDE-47/2'
      MeO-BDE-68 and brassicasterol/dinosterol indicate that the signature of MeO-BDEs
      is controlled by the phytoplankton community structure. 

PMID- 24874794
TI  - Earthworm tolerance to residual agricultural pesticide contamination: field and
      experimental assessment of detoxification capabilities.
AB  - This study investigates if acclimatization to residual pesticide contamination in
      agricultural soils is reflected in detoxification, antioxidant enzyme activities
      and energy budget of earthworms. Five fields within a joint agricultural area
      exhibited different chemical and farming histories from conventional cultivation
      to organic pasture. Soil multiresidual pesticide analysis revealed up to 9
      molecules including atrazine up to 2.4 ng g(-1) dry soil. Exposure history of
      endogeic Aporrectodea caliginosa and Allolobophora chlorotica modified their
      responses to pesticides. In the field, activities of soluble glutathione-S
      transferases (sGST) and catalase increased with soil pesticide contamination in
      A. caliginosa. Pesticide stress was reflected in depletion of energy reserves in
      A. chlorotica. Acute exposure of pre-adapted and naive A. caliginosa to
      pesticides (fungicide Opus((r)), 0.1 MUg active ingredient epoxiconazole g(-1)
      dry soil, RoundUp Flash((r)), 2.5 MUg active ingredient glyphosate g(-1) dry
      soil, and their mixture), revealed that environmental pre-exposure accelerated
      activation of the detoxification enzyme sGST towards epoxiconazole. 

PMID- 24874795
TI  - Toward product attribute control: developments from genome sequencing.
AB  - Chinese hamster ovary (CHO) cells are important hosts for the production of
      therapeutic proteins. Recent genome sequencing studies provide an initial
      baseline of information useful for understanding cell line performance in terms
      of product quality attributes. However, the lack of a well-established reference
      genome together with concerns about genome stability have not yet permitted the
      community to define the detailed relationship between the genome and cell line
      performance. Emerging efforts to define a new reference genome, together with new
      data on genome stability, herald an era where cell line's with defined genomes
      can be combined with defined process parameters to yield product quality
      attribute control. 

PMID- 24874797
TI  - A colorimetric and ratiometric fluorescent probe for the imaging of endogenous
      hydrogen sulphide in living cells and sulphide determination in mouse
      hippocampus.
AB  - A naphthalimide-azide based colorimetric and ratiometric fluorescent probe, NAP
      1, has been developed for the selective and sensitive detection of hydrogen
      sulphide. Advantages of the probe NAP-1 include a low detection limit (110 nM),
      good selectivity, high sensitivity and excellent photostability. A linear
      relationship between the emission intensity ratios and sulphide concentrations
      was observed in PBS buffer and bovine serum, respectively. Our probe facilitates
      ratiometric determination and imaging of endogenous H2S in living cells.
      Furthermore, this probe was successfully applied to the measurement of endogenous
      sulphide in human plasma and mouse hippocampus. A significant reduction in
      sulphide levels and CBS mRNA expression was observed in the hippocampus of mouse
      models of lipopolysaccharide-induced neuroinflammation-related diseases,
      suggesting that decreased levels of endogenous H2S might be involved in the
      pathogenesis of neuroinflammation-related neurodegenerative diseases. 

PMID- 24874796
TI  - Using molecular epidemiology to track Toxoplasma gondii from terrestrial
      carnivores to marine hosts: implications for public health and conservation.
AB  - BACKGROUND: Environmental transmission of the zoonotic parasite Toxoplasma
      gondii, which is shed only by felids, poses risks to human and animal health in
      temperate and tropical ecosystems. Atypical T. gondii genotypes have been linked
      to severe disease in people and the threatened population of California sea
      otters. To investigate land-to-sea parasite transmission, we screened 373
      carnivores (feral domestic cats, mountain lions, bobcats, foxes, and coyotes) for
      T. gondii infection and examined the distribution of genotypes in 85 infected
      animals sampled near the sea otter range. METHODOLOGY/PRINCIPAL FINDINGS: Nested
      PCR-RFLP analyses and direct DNA sequencing at six independent polymorphic
      genetic loci (B1, SAG1, SAG3, GRA6, L358, and Apico) were used to characterize T.
      gondii strains in infected animals. Strains consistent with Type X, a novel
      genotype previously identified in over 70% of infected sea otters and four
      terrestrial wild carnivores along the California coast, were detected in all
      sampled species, including domestic cats. However, odds of Type X infection were
      14 times higher (95% CI: 1.3-148.6) for wild felids than feral domestic cats.
      Type X infection was also linked to undeveloped lands (OR = 22, 95% CI: 2.3
      250.7). A spatial cluster of terrestrial Type II infection (P = 0.04) was
      identified in developed lands bordering an area of increased risk for sea otter
      Type II infection. Two spatial clusters of animals infected with strains
      consistent with Type X (P <= 0.01) were detected in less developed landscapes.
      CONCLUSIONS: Differences in T. gondii genotype prevalence among domestic and wild
      felids, as well as the spatial distribution of genotypes, suggest co-existing
      domestic and wild T. gondii transmission cycles that likely overlap at the
      interface of developed and undeveloped lands. Anthropogenic development driving
      contact between these cycles may increase atypical T. gondii genotypes in
      domestic cats and facilitate transmission of potentially more pathogenic
      genotypes to humans, domestic animals, and wildlife.

PMID- 24874798
TI  - OECD validation study to assess intra- and inter-laboratory reproducibility of
      the zebrafish embryo toxicity test for acute aquatic toxicity testing.
AB  - The OECD validation study of the zebrafish embryo acute toxicity test (ZFET) for
      acute aquatic toxicity testing evaluated the ZFET reproducibility by testing 20
      chemicals at 5 different concentrations in 3 independent runs in at least 3
      laboratories. Stock solutions and test concentrations were analytically confirmed
      for 11 chemicals. Newly fertilised zebrafish eggs (20/concentration and control)
      were exposed for 96h to chemicals. Four apical endpoints were recorded daily as
      indicators of acute lethality: coagulation of the embryo, lack of somite
      formation, non-detachment of the tail bud from the yolk sac and lack of
      heartbeat. Results (LC50 values for 48/96h exposure) show that the ZFET is a
      robust method with a good intra- and inter-laboratory reproducibility (CV<30%)
      for most chemicals and laboratories. The reproducibility was lower (CV>30%) for
      some very toxic or volatile chemicals, and chemicals tested close to their limit
      of solubility. The ZFET is now available as OECD Test Guideline 236. Considering
      the high predictive capacity of the ZFET demonstrated by Belanger et al. (2013)
      in their retrospective analysis of acute fish toxicity and fish embryo acute
      toxicity data, the ZFET is ready to be considered for acute fish toxicity for
      regulatory purposes.

PMID- 24874800
TI  - Polyphosphate, cyclic AMP, guanosine tetraphosphate, and c-di-GMP reduce in vitro
      Lon activity.
AB  - Lon protease is conserved from bacteria to humans and regulates cellular
      processes by degrading different classes of proteins including antitoxins,
      transcriptional activators, unfolded proteins, and free ribosomal proteins. Since
      we found that Lon has several putative cyclic diguanylate (c-di-GMP) binding
      sites and since Lon binds polyphosphate (polyP) and lipid polysaccharide, we
      hypothesized that Lon has an affinity for phosphate-based molecules that might
      regulate its activity. Hence we tested the effect of polyP, cyclic adenosine
      monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), guanosine
      tetraphosphate (ppGpp), c-di-GMP, and GMP on the ability of Lon to degrade alpha
      casein. Inhibition of in vitro Lon activity occurred for polyP, cAMP, ppGpp, and
      c-di-GMP. We also demonstrated by HPLC that Lon is able to bind c-di-GMP.
      Therefore, four cell signals were found to regulate the activity of Lon protease.

PMID- 24874799
TI  - The PhoP-dependent ncRNA Mcr7 modulates the TAT secretion system in Mycobacterium
      tuberculosis.
AB  - The PhoPR two-component system is essential for virulence in Mycobacterium
      tuberculosis where it controls expression of approximately 2% of the genes,
      including those for the ESX-1 secretion apparatus, a major virulence determinant.
      Mutations in phoP lead to compromised production of pathogen-specific cell wall
      components and attenuation both ex vivo and in vivo. Using antibodies against the
      native protein in ChIP-seq experiments (chromatin immunoprecipitation followed by
      high-throughput sequencing) we demonstrated that PhoP binds to at least 35 loci
      on the M. tuberculosis genome. The PhoP regulon comprises several transcriptional
      regulators as well as genes for polyketide synthases and PE/PPE proteins.
      Integration of ChIP-seq results with high-resolution transcriptomic analysis (RNA
      seq) revealed that PhoP controls 30 genes directly, whilst regulatory cascades
      are responsible for signal amplification and downstream effects through proteins
      like EspR, which controls Esx1 function, via regulation of the espACD operon. The
      most prominent site of PhoP regulation was located in the intergenic region
      between rv2395 and PE_PGRS41, where the mcr7 gene codes for a small non-coding
      RNA (ncRNA). Northern blot experiments confirmed the absence of Mcr7 in an M.
      tuberculosis phoP mutant as well as low-level expression of the ncRNA in M.
      tuberculosis complex members other than M. tuberculosis. By means of genetic and
      proteomic analyses we demonstrated that Mcr7 modulates translation of the tatC
      mRNA thereby impacting the activity of the Twin Arginine Translocation (Tat)
      protein secretion apparatus. As a result, secretion of the immunodominant Ag85
      complex and the beta-lactamase BlaC is affected, among others. Mcr7, the first
      ncRNA of M. tuberculosis whose function has been established, therefore
      represents a missing link between the PhoPR two-component system and the
      downstream functions necessary for successful infection of the host. 

PMID- 24874801
TI  - Potential biological and ecological effects of flickering artificial light.
AB  - Organisms have evolved under stable natural lighting regimes, employing cues from
      these to govern key ecological processes. However, the extent and density of
      artificial lighting within the environment has increased recently, causing
      widespread alteration of these regimes. Indeed, night-time electric lighting is
      known significantly to disrupt phenology, behaviour, and reproductive success,
      and thence community composition and ecosystem functioning. Until now, most
      attention has focussed on effects of the occurrence, timing, and spectral
      composition of artificial lighting. Little considered is that many types of lamp
      do not produce a constant stream of light but a series of pulses. This flickering
      light has been shown to have detrimental effects in humans and other species.
      Whether a species is likely to be affected will largely be determined by its
      visual temporal resolution, measured as the critical fusion frequency. That is
      the frequency at which a series of light pulses are perceived as a constant
      stream. Here we use the largest collation to date of critical fusion frequencies,
      across a broad range of taxa, to demonstrate that a significant proportion of
      species can detect such flicker in widely used lamps. Flickering artificial light
      thus has marked potential to produce ecological effects that have not previously
      been considered. 

PMID- 24874806
TI  - PINK1-Parkin pathway activity is regulated by degradation of PINK1 in the
      mitochondrial matrix.
AB  - Loss-of-function mutations in PINK1, which encodes a mitochondrially targeted
      serine/threonine kinase, result in an early-onset heritable form of Parkinson's
      disease. Previous work has shown that PINK1 is constitutively degraded in healthy
      cells, but selectively accumulates on the surface of depolarized mitochondria,
      thereby initiating their autophagic degradation. Although PINK1 is known to be a
      cleavage target of several mitochondrial proteases, whether these proteases
      account for the constitutive degradation of PINK1 in healthy mitochondria remains
      unclear. To explore the mechanism by which PINK1 is degraded, we performed a
      screen for mitochondrial proteases that influence PINK1 abundance in the fruit
      fly Drosophila melanogaster. We found that genetic perturbations targeting the
      matrix-localized protease Lon caused dramatic accumulation of processed PINK1
      species in several mitochondrial compartments, including the matrix. Knockdown of
      Lon did not decrease mitochondrial membrane potential or trigger activation of
      the mitochondrial unfolded protein stress response (UPRmt), indicating that PINK1
      accumulation in Lon-deficient animals is not a secondary consequence of
      mitochondrial depolarization or the UPRmt. Moreover, the influence of Lon on
      PINK1 abundance was highly specific, as Lon inactivation had little or no effect
      on the abundance of other mitochondrial proteins. Further studies indicated that
      the processed forms of PINK1 that accumulate upon Lon inactivation are capable of
      activating the PINK1-Parkin pathway in vivo. Our findings thus suggest that Lon
      plays an essential role in regulating the PINK1-Parkin pathway by promoting the
      degradation of PINK1 in the matrix of healthy mitochondria.

PMID- 24874809
TI  - One-pot Stober route yields template for Ag@carbon yolk-shell nanostructures.
AB  - A facile one-pot Stober route is used to synthesize high-quality Ag, AgBr-silica
      resorcinol formaldehyde polymer core-shell-shell nanospheres. The obtained core
      shell-shell templates can be converted to Ag@carbon yolk-shell nanostructures
      with tunable dimensions. 

PMID- 24874805
TI  - Small bowel bleeding: a comprehensive review.
AB  - The small intestine is an uncommon site of gastro-intestinal (GI) bleeding;
      however it is the commonest cause of obscure GI bleeding. It may require multiple
      blood transfusions, diagnostic procedures and repeated hospitalizations.
      Angiodysplasia is the commonest cause of obscure GI bleeding, particularly in the
      elderly. Inflammatory lesions and tumours are the usual causes of small
      intestinal bleeding in younger patients. Capsule endoscopy and deep enteroscopy
      have improved our ability to investigate small bowel bleeds. Deep enteroscopy has
      also an added advantage of therapeutic potential. Computed tomography is helpful
      in identifying extra-intestinal lesions. In cases of difficult diagnosis, surgery
      and intra-operative enteroscopy can help with diagnosis and management. The
      treatment is dependent upon the aetiology of the bleed. An overt bleed requires
      aggressive resuscitation and immediate localisation of the lesion for institution
      of appropriate therapy. Small bowel bleeding can be managed by conservative,
      radiological, pharmacological, endoscopic and surgical methods, depending upon
      indications, expertise and availability. Some patients, especially those with
      multiple vascular lesions, can re-bleed even after appropriate treatment and pose
      difficult challenge to the treating physician. 

PMID- 24874807
TI  - The macroecology of airborne pollen in Australian and New Zealand urban areas.
AB  - The composition and relative abundance of airborne pollen in urban areas of
      Australia and New Zealand are strongly influenced by geographical location,
      climate and land use. There is mounting evidence that the diversity and quality
      of airborne pollen is substantially modified by climate change and land-use yet
      there are insufficient data to project the future nature of these changes. Our
      study highlights the need for long-term aerobiological monitoring in Australian
      and New Zealand urban areas in a systematic, standardised, and sustained way, and
      provides a framework for targeting the most clinically significant taxa in terms
      of abundance, allergenic effects and public health burden. 

PMID- 24874808
TI  - Ectopic integration vectors for generating fluorescent promoter fusions in
      Bacillus subtilis with minimal dark noise.
AB  - Fluorescent protein promoter reporters are important tools that are widely used
      for diverse purposes in microbiology, systems biology and synthetic biology and
      considerable engineering efforts are still geared at improving the sensitivity of
      the reporter systems. Here we focus on dark noise, i.e. the signal that is
      generated by the empty vector control. We quantitatively characterize the dark
      noise of a few common bacterial reporter systems by single cell microscopy. All
      benchmarked reporter systems generated significant amounts of dark noise that
      exceed the cellular autofluorescence to different extents. We then reengineered a
      multicolor set of fluorescent ectopic integration vectors for Bacillus subtilis
      by introducing a terminator immediately upstream of the promoter insertion site,
      resulting in an up to 2.7-fold reduction of noise levels. The sensitivity and
      dynamic range of the new high-performance pXFP_Star reporter system is only
      limited by cellular autofluorescence. Moreover, based on studies of the rapE
      promoter of B. subtilis we show that the new pXFP_Star reporter system reliably
      reports on the weak activity of the rapE promoter whereas the original reporter
      system fails because of transcriptional interference. Since the pXFP_Star
      reporter system properly isolates the promoter from spurious transcripts, it is a
      particularly suitable tool for quantitative characterization of weak promoters in
      B. subtilis. 

PMID- 24874810
TI  - Peripheral neuropathy in children on stauvudine therapy.
AB  - OBJECTIVE: To assess the prevalence of peripheral neuropathy in HIV infected
      children (>5 y) receiving stavudine-based combination anti-retroviral treatment
      (ART) for more than 3 mo in a cross-sectional study. METHODS: History, detailed
      neurological examination and nerve conduction studies were performed. RESULTS:
      Forty children [26 boys; median age - 11.75 y, Inter quartile range (IQR): 9-16
      y] were enrolled. The median duration of ART was 43 mo [IQR: 18-69 mo]. The nerve
      conduction studies were abnormal in four children (10 %). Symptomatic distal
      sensory polyneuropathy was present in two children, asymptomatic distal sensory
      polyneuropathy and subclinical distal sensory polyneuropathy was present in one
      child each. CONCLUSIONS: Distal sensory polyneuropathy is a potential problem in
      children on stavudine based ART. Children on stavudine based ART need periodic
      clinical and electrophysiological screening for its early detection.

PMID- 24874811
TI  - Illness burden, care seeking, and treatment cost among less than 2-year-olds in
      rural Haryana.
AB  - OBJECTIVE: To estimate illness burden, treatment sources, and out-of-pocket (OOP)
      expenditures among <2-y-olds as mortality is higher in this age group. METHODS:
      This prospective study was conducted in rural area of Haryana from January
      through June 2007. At baseline, 6828 children (<2-y-olds) were enrolled from 169
      villages of Khizrabad block in Haryana. Thirty trained volunteers interviewed
      their mothers/caretakers at fortnightly interval to record symptoms and signs of
      illnesses occurring in past two weeks and the treatment sought. Five supervisors
      obtained data on Out-of-Pocket (OOP) expenditures from 20 % randomly selected
      households who had reported illness. The main outcome measures were illness
      burden, treatment sources and OOP expenditures. RESULTS: Overall, 8 %
      (4,893/60,910) of the <2-y-olds suffered from illness during 12 fortnightly
      surveys. Incidence was estimated to be 2.1 episodes per child per year. Acute
      respiratory infections (ARI) and diarrhea were the leading illnesses (66.3 % and
      19.4 % respectively). Most (98 %) had consulted a health care provider. Village
      practitioners were the major (71 %) healthcare providers. About 12 % of the
      children were hospitalized. Consultations were mostly (98 %) with private medical
      practitioners. Average OOP expenditure was Rs. 444 (95 % CI 299 to 589) per
      episode; Rs. 203 (95 % CI 188 to 232) and Rs. 5,734 (95%CI 3,336 to 8,131) in the
      out-patient and in-patient department respectively. CONCLUSIONS: ARI and diarrhea
      continue to be the commonest illness among <2-y-olds. Most patients seek care in
      private sector and pay for the treatment from out-of-pocket source. Access to
      healthcare needs to be enhanced in public sector to reduce the financial burden.

PMID- 24874812
TI  - Perfusion decellularization of whole organs.
AB  - The native extracellular matrix (ECM) outlines the architecture of organs and
      tissues. It provides a unique niche of composition and form, which serves as a
      foundational scaffold that supports organ-specific cell types and enables normal
      organ function. Here we describe a standard process for pressure-controlled
      perfusion decellularization of whole organs for generating acellular 3D scaffolds
      with preserved ECM protein content, architecture and perfusable vascular
      conduits. By applying antegrade perfusion of detergents and subsequent washes to
      arterial vasculature at low physiological pressures, successful decellularization
      of complex organs (i.e., hearts, lungs and kidneys) can be performed. By using
      appropriate modifications, pressure-controlled perfusion decellularization can be
      achieved in small-animal experimental models (rat organs, 4-5 d) and scaled to
      clinically relevant models (porcine and human organs, 12-14 d). Combining the
      unique structural and biochemical properties of native acellular scaffolds with
      subsequent recellularization techniques offers a novel platform for organ
      engineering and regeneration, for experimentation ex vivo and potential clinical
      application in vivo. 

PMID- 24874813
TI  - Antibiotic resistance-mediated isolation of scaffold-specific natural product
      producers.
AB  - For over half a century, actinomycetes have served as the most promising source
      of novel antibacterial scaffolds. However, over the years, there has been a
      decline in the discovery of new antibiotics from actinomycetes. This is partly
      due to the use of standard screening methods and platforms that result in the re
      discovery of the same molecules. Thus, according to current estimates, the
      discovery of a new antibacterial requires screening of tens to hundreds of
      thousands of bacterial strains. We have devised a resistance-based antibacterial
      discovery platform by harnessing the innate self-protection mechanism of
      antibiotic producers. This protocol provides a detailed method for isolation of
      scaffold-specific antibacterial producers by isolating strains in the presence of
      a selective antibiotic. As a specific example, we describe isolation of
      glycopeptide antibiotic (GPA) producers from soil actinomycetes, using vancomycin
      as the antibiotic resistance filter. However, the protocol can be adapted to
      isolate diverse producers from various sources producing different scaffolds, by
      selecting an appropriate antibiotic as a screening filter. The protocol provides
      a solution for two major bottlenecks that impede the new drug discovery pipeline:
      low hit frequency and re-discovery of known molecules. The entire protocol, from
      soil collection to identification of putative antibacterial producers, takes
      about 6 weeks to complete. 

PMID- 24874814
TI  - Capture of activity-induced ultrastructural changes at synapses by high-pressure
      freezing of brain tissue.
AB  - Electron microscopy (EM) allows for the simultaneous visualization of all tissue
      components at high resolution. However, the extent to which conventional aldehyde
      fixation and ethanol dehydration of the tissue alter the fine structure of cells
      and organelles, thereby preventing detection of subtle structural changes induced
      by an experiment, has remained an issue. Attempts have been made to rapidly
      freeze tissue to preserve native ultrastructure. Shock-freezing of living tissue
      under high pressure (high-pressure freezing, HPF) followed by cryosubstitution of
      the tissue water avoids aldehyde fixation and dehydration in ethanol; the tissue
      water is immobilized in ~50 ms, and a close-to-native fine structure of cells,
      organelles and molecules is preserved. Here we describe a protocol for HPF that
      is useful to monitor ultrastructural changes associated with functional changes
      at synapses in the brain but can be applied to many other tissues as well. The
      procedure requires a high-pressure freezer and takes a minimum of 7 d but can be
      paused at several points. 

PMID- 24874815
TI  - Resolving genomic disorder-associated breakpoints within segmental DNA
      duplications using massively parallel sequencing.
AB  - The most common recurrent copy-number variants associated with autism,
      developmental delay and epilepsy are flanked by segmental duplications. Complete
      genetic characterization of these events is challenging because their breakpoints
      often occur within high-identity, copy-number polymorphic paralogous sequences
      that cannot be specifically assayed using hybridization-based methods. Here we
      provide a protocol for breakpoint resolution with sequence-level precision.
      Massively parallel sequencing is performed on libraries generated from haplotype
      resolved chromosomes, genomic DNA or molecular inversion probe (MIP)-captured
      breakpoint-informative regions harboring paralog-distinguishing variants.
      Quantification of sequencing depth over informative sites enables breakpoint
      localization, typically within several kilobases to tens of kilobases. Depending
      on the approach used, the sequencing platform, and the accuracy and completeness
      of the reference genome sequence, this protocol takes from a few days to several
      months to complete. Once established for a specific genomic disorder, it is
      possible to process thousands of DNA samples within as little as 3-4 weeks. 

PMID- 24874817
TI  - Addendum: A reproducible and well-tolerated method for 2/3 partial hepatectomy in
      mice.

PMID- 24874818
TI  - Highly conducting lyotropic liquid crystalline mesophases of pluronics (P65, P85,
      P103, and P123) and hydrated lithium salts (LiCl and LiNO3).
AB  - Demand for ionically conducting materials, as membranes and electrodes, is one of
      the driving forces of current research in chemistry, physics, and engineering.
      The lithium ion is a key element of these materials, and its assembly into
      nanostructures and mesophases is important for the membrane and electrode
      technologies. In this investigation, we show that hydrated lithium salts (such as
      LiCl.xH2O and LiNO3.xH2O, x is as low as 1.5 and 3.0, respectively) and pluronics
      (triblock copolymer such as PX where X is 65, 85, 103, and 123) form lyotropic
      liquid crystalline mesophases (LLCM), denoted as LiY.xH2O-PX-n (Y is Cl(-) or
      NO3(-), and n is the salt/PX mole ratio). The structure of the mesophase is
      hexagonal over a broad salt concentration and transforms to a cubic mesophase and
      then to disordered gel phase with an increasing salt content of the mixtures. The
      mesophases are unstable at low salt contents and undergo a phase separation into
      pure pluronics and salt-rich LLCMs. The salt content of the ordered mesophase can
      be as high as 30 mole ratio for each pluronic, which is a record high for any
      known salted phases. The mesophases also display high ac ionic conductivities,
      reaching up to 21 mS/cm at room temperature (RT), and are sensitive to the water
      content. These mesophases can be useful as ion-conducting membranes and can be
      used as media for the synthesis of lithium-containing nanoporous materials. 

PMID- 24874816
TI  - Generation, expansion and functional analysis of endothelial cells and pericytes
      derived from human pluripotent stem cells.
AB  - Human endothelial cells (ECs) and pericytes are of great interest for research on
      vascular development and disease, as well as for future therapy. This protocol
      describes the efficient generation of ECs and pericytes from human pluripotent
      stem cells (hPSCs) under defined conditions. Essential steps for hPSC culture,
      differentiation, isolation and functional characterization of ECs and pericytes
      are described. Substantial numbers of both cell types can be derived in only 2-3
      weeks: this involves differentiation (10 d), isolation (1 d) and 4 or 10 d of
      expansion of ECs and pericytes, respectively. We also describe two assays for
      functional evaluation of hPSC-derived ECs: (i) primary vascular plexus formation
      upon coculture with hPSC-derived pericytes and (ii) incorporation in the
      vasculature of zebrafish xenografts in vivo. These assays can be used to test the
      quality and drug sensitivity of hPSC-derived ECs and model vascular diseases with
      patient-derived hPSCs. 

PMID- 24874820
TI  - The specificity of interaction of Zn(2+), Ni(2+) and Cu(2+) ions with the
      histidine-rich domain of the TjZNT1 ZIP family transporter.
AB  - The Zrt/Irt-like protein (ZIP) family contributes to the metal homeostasis by
      regulating the transport of divalent metal cations such as Fe(2+), Zn(2+),
      Mn(2+), Cd(2+) and sometimes even Cu(2+). Most ZIP members have a long variable
      loop between transmembrane domains (TMDs) III and IV; this region is predicted to
      be located in the cytoplasm and is postulated to be the metal ion binding site.
      In this study, we looked at the thermodynamic behavior and coordination chemistry
      of Zn(2+), Ni(2+) and Cu(2+) complexes with the histidine-rich domain, Ac
      (185)RAHAAHHRHSH(195)-NH2 (HRD), from the yeast TjZNT1 protein, located between
      TMDs III and IV. The sequence is conserved also in higher species like Thlaspi
      japonicum. The stability of complexes increases in the series Ni(2+) < Zn(2+)?
      Cu(2+). The geometry of complexes is very different for each metal and in the
      case of Zn(2+) complexes, high specificity in binding is observed. Moreover, the
      stability of HRD-Cu(2+) complexes was compared with the five His residues
      containing peptide from Hpn protein (Helicobacter pylori). The results suggest a
      high ability of HRD in the binding of all three studied metals. 

PMID- 24874819
TI  - Structures of protonated thymine and uracil and their monohydrated gas-phase ions
      from ultraviolet action spectroscopy and theory.
AB  - The strong UV chromophores thymine (Thy) and uracil (Ura) have identical
      heteroaromatic rings that only differ by one methyl substituent. While their
      photophysics has been elucidated in detail, the effect on the excited states of
      base protonation and single water molecules is less explored. Here we report gas
      phase absorption spectra of ThyH(+) and UraH(+) and monohydrated ions and
      demonstrate that the substituent is not only responsible for spectral shifts but
      also influences the tautomer distribution, being different for bare and
      monohydrated ions. Spectra interpretation is aided by calculations of geometrical
      structures and transition energies. The lowest free-energy tautomer (denoted 178,
      enol-enol form) accounts for 230-280 nm (ThyH(+)) and 225-270 nm (UraH(+)) bands.
      ThyH(+) hardly absorbs above 300 nm, whereas a discernible band is measured for
      UraH(+) (275-320 nm), ascribed to the second lowest free-energy tautomer (138,
      enol-keto form) comprising a few percent of the UraH(+) population at room
      temperature. Band widths are similar to those measured of cold ions in support of
      very short excited-state lifetimes. Attachment of a single water increases the
      abundance of 138 relative to 178, 138 now clearly present for ThyH(+). 138
      resembles more the tautomer present in aqueous solution than 178 does, and 138
      may indeed be a relevant transition structure. The band of ThyH(+)(178) is
      unchanged, that of UraH(+)(178) is nearly unchanged, and that of UraH(+)(138)
      blue-shifts by about 10 nm. In stark contrast to protonated adenine, more than
      one solvating water molecule is required to re-establish the absorption of
      ThyH(+) and UraH(+) in aqueous solution. 

PMID- 24874821
TI  - [Role of prebioptic and bioptic methodsin the screening and diagnosis of cervical
      cancer].
AB  - OBJECTIVE: To describe the available prebioptical and bioptical methods used in
      screening and diagnosis of cervical cancer. DESIGN: Review article. SETTING:
      Center of outpatient gynecology and primary care, Brno; Department of Obstetrics
      and Gynecology, University Hospital, Olomouc.Subjects and methods of the study:
      In a review article there are outlines of the prebioptical investigative
      techniques and related diagnostics aim to detect, verificate and treat cervical
      lesions. It describes and compares various methods, including their mutual
      correlation. CONCLUSION: The oncological cytology, colposcopy and HPV testing
      have an irreplaceable role in diagnosis of cervical cancer. Appropriate
      combination gives us a chance to achieve high sensitivity in detection of severe
      lesions of the cervix.

PMID- 24874822
TI  - [Ovarian epithelial malignant tumors in adolescence].
AB  - OBJECTIVE: Ovarian epithelial malignant tumors in adolescence. DESIGN: Literature
      review with case reports. SETTING: Department of Gynaecology and Obstetrics,
      Faculty of Medicine at Masaryk's University and Fakulty Hospital Brno. METHODS:
      Literature review on ovarian epithelial malignant tumors in adolescence, their
      epidemiology, diagnosis and therapy with illustrative case reports. CONCLUSION:
      The ovarian epithelial malignant tumors in the adolescence represent rare group
      of these diseases according to the data from the National Cancer Registry.
      However, it is a very sensitive area of oncogynecology, that requires highly
      personalized approach and the cooperation with patient's family. The ovarian
      epithelial malignant tumors in the age group of 15-19 years show some differences
      from these diseases of adults and older women. The differences concern the extent
      of the disease at the time of the diagnosis, the histopathological
      characteristics of the tumors and the proportion surgical therapy and
      chemotherapy. The diagnostic algorithm requires the cooperation with the
      colleagues from pediatric gynecology and oncology. Due to the occurrence of
      localizated stages and good tumor differentiation prevails the monotherapy
      presented the surgical treatment, especially in the form of the radical fertility
      preserving procedures. The care of the patients should be concentrated into the
      oncogynecological centres.

PMID- 24874823
TI  - [Role of fatty acids in sperm membrane].
AB  - One of causes of male infertility is reduced sperm motility. Reactive oxygen
      species (ROS) play significant role for physiological sperm function. Oxidative
      stress occurs when the production of potentially destructive ROS exceeds the
      natural antioxidant defences, resulting in cell damage. Sperm phospholipid
      polyunsaturated fatty acids are particularly susceptible to peroxidative damage
      by free radicals. Detrimental effects of lipid peroxidation should decrease sperm
      quality and be responsible of fertility problems. The review deals with sperm
      membrane composition, importance of fatty acids and prevention possibilities of
      oxidative cell damage.

PMID- 24874824
TI  - [Breech presentation - an analysis of results in one perinatal center].
AB  - OBJECTIVE: A retrospective analysis of medical records during years 2007-2011
      considers maternal and fetal outcome in patients with breech presentation
      terminated by vaginal delivery versus caesarean section (CS). DESIGN:
      Retrospective analysis. SETTING: Department of Gynecology and Obstetrics,
      Jessenius Faculty of Medicine, Comenius University, Martin, Slovak Republic.
      METHODS: Authors devided patients with breech presentation of fetus (n = 299) to
      groups of single pregnancies terminated in term (n = 197), before term (n = 67)
      and to group of multiple pregnancies (n = 35). All groups were devided according
      to the way of termination of pregnancy by vaginal delivery, by acute CS and by
      planned CS. Main followed parameters: parity, gestational week, Apgar score,
      birth weight, birth length, fetal gender, indications for CS, mortality and
      neonatal morbidity, umbilical artery pH, convulsions, admit to neonatal intensive
      care unit, intubation of neonate, intracranial bleeding, cervical spine and
      peripheral nerve injuries. RESULTS: Total cohort of breech deliveries was 299. In
      the group of single pregnancies in term was 19.8% terminated by vaginal delivery
      (n = 39), 32.5% deliveries by acute CS (n = 64). The most common indication was
      fetal hypoxia (43.8%). By planned CS was terminated 47.7% deliveries (n = 94).
      The most common indication for CS was footling presentation (54.3%). Severe
      neonatal morbidity was rare and without significant difference according to the
      type of termination of pregnancy. Neonatal outcome was comparable in the group of
      preterm deliveries(n = 67) terminated by vaginal delivery or by CS. All neonatal
      deaths were associated with extreme prematurity and not with type of termination
      of gravidity. CONCLUSION: Clinical outcomes between vaginal breech deliveries and
      breech deliveries terminated by CS in term in singleton pregnancies were not
      significant different. Mortality of neonates delivered by preterm delivery was
      associated with severe prematurity.

PMID- 24874825
TI  - [Effect of resilience in women on the outcome of her first IVF/ICSI].
AB  - OBJECTIVE: To examine whether women's well-being and coping strategies are
      associated with IVF outcomes. DESIGN: Prospective study. SETTING: Centre of
      assisted reproduction Sanus, Pardubice; PPCHC s.r.o. Hradec KraloveMethods: Study
      included these methods of data collection; Psychological well-being was mesured
      by Dotaznik zivotni spokojenosti (Questionnaire of well-being,n = 103) and coping
      strategies were mesured by COPE Invetory (n = 82). In the years 2010-2013 women
      attending their first cycle IVF/ICSI (younger than 35 years) were asked to fill
      in the psychological questionnaires prior to collection of oocytes. Then the
      result of IVF/ICSI was observed - a clinically recognized pregnancy. We compared
      general well-being, satisfaction with their own health, marital satisfaction and
      emotion focused coping strategies: Acceptance, Positive reinterpretation and
      Seeking of emotional social support, between pregnant and non-pregnant women.
      RESULTS: There were no statistically significant differences between women who
      became pregnant and those who did not in general well-being (t = -0.9,p = 0.37),
      satisfaction with their own health (t = -0.6, p = 0.52), marital satisfaction (t
      = -0.8, p = 0.44), use of Acceptance (t = 0.9 , p = 0.36) and Positive
      reinterpretation (t = -0.8, p = 0.43). The only factor that was significantly
      associated with pregnancy outcome was Seeking of emotional social support (t =
      2.3, p = 0.02). CONCLUSION: We found no evidence that psychological well-being
      had any influence on the outcome of IVF/ICSI treatment. In case of emotion
      focused coping we found that women who became pregnant used significantly more
      often strategy called Seeking of emotional social support than women who remained
      nonpregnant.

PMID- 24874826
TI  - [Intrauterine fetal death syndrome: analysis of cases from 2008 to 2012 in
      Institute for the care of mother and child].
AB  - OBJECTIVE: We made an analysis of number of intrauterine fetal deaths in our
      institute, it's causes, risk factors and patient's main complaints. METHODS:
      Retrospective study of all intrauterine fetal deaths in Institute for the care of
      mother and child in years 2008-2012. RESULTS: We had 60 cases of intrauterine
      fetal death from 2008 to 2012 which represented 2.4 of all deliveries (24884).
      The examination started in 45% of cases due to information about decreased fetal
      movements, 28.3% was diagnosed during regular visit, 13.3% came for contractions,
      10% because of PPROM and 3.3% due to vaginal bleeding. In 58.3% we used induction
      of delivery, in 10% delivery started spontaneously and in 31.7% a caesarean
      section was performed. CONCLUSION: Decrease in fetal movements was the most
      frequent complaint of our patients. Spontaneously delivered 68.3% patients,
      caesarean section was indicated in twins, due to maternal diseases or from vital
      indication. In 70% of cases we approved the cause of intrauterine fetal death.
      Mostly umbilical cord or placental abnormalities were present.

PMID- 24874827
TI  - Highly active antiretroviral therapy during gestation: effects on a rat model of
      pregnancy.
AB  - OBJECTIVE: To assess the adverse effects of the chronic use of
      zidovudine/lopinavir/ritonavir in a rat pregnancy model.Type of article: Original
      paper. DESIGN: A prospective experimental study. SETTING: Department of
      Obstetrics, Sao Paulo Federal University (UNIFESP). METHODS: 40 pregnant EPM-1
      albino rats were randomly allocated into four groups of 10 animals each: control
      (Ctrl) group (untreated) and three experimental groups (Exp1, Exp2 and Exp3),
      which received zidovudine/lopinavir/ritonavir in the corresponding doses of
      10/13.3/3.3; 30/39.9/9.9 and 90/119.7/29.7 mg/Kg/day from the first up to the
      20th day of pregnancy, respectively. The rats were treated by gavage daily. Body
      weights were recorded on days 0, 7, 14 and 20. At term, the rats were sacrificed
      and the implantation sites, number of live and dead fetuses and placentas,
      resorptions and fetal and placental weights were recorded. The fetuses were
      evaluated for external abnormalities under a stereomicroscope. The chi-square
      test was used to compare death rates between groups. RESULTS: Weight gain during
      pregnancy no showed significant differences between groups. Average weight gains
      between the 7th and 20th day were 45.70 +/- 5.27 g for Ctrl; 48.49 +/- 3.64 g for
      Exp1; 45.39 +/- 6.22 g for Exp2 and 44.19 +/- 6.78 g for Exp3. However, the
      percentage weight gain in the 7th was lower in groups Exp2 and Exp3 and in the
      14th in the Group Exp2. All other parameters assessed did not differ
      significantly between groups. Exp2 and Exp3 in relation of the others.
      CONCLUSIONS: The chronic exposure of pregnant rats to high doses of
      zidovudine/lopinavir/ritonavir in association resulted in a significant reduction
      in maternal body weight gain but was not associated with significant adverse
      fetal parameters.

PMID- 24874828
TI  - [Folic acid and prevention of the neural tube defects].
AB  - OBJECTIVE: Overview of neural tube defect in relation to use of folic acid among
      fertile-age women. DESIGN: Review article. SETTING: Obstetrics and gynecology
      department OU and FN Ostrava. METHODS AND RESULTS: Neural tube defects (NTDs) are
      one of the most common birth defects in the Czech Republic. The relation between
      using of folic acid and decrease of the incidence NTDs was first described in
      1965. Fertile-age women are not able to get enough folate from their diet,
      therefore right timing and proper dosing of folic acid is the object of numerous
      studies. Many countries started theirs food fortification programs because of the
      high percentage of unplanned pregnancies and often low compliance. CONCLUSION:
      The role of folic acid in prevention of NTDs is undeniable. Due to the large
      number of unplanned pregnancies long-term supplementation is recommended for all
      fertile-age women. If pregnancy is planned, the suplementation should begin at
      least one month before pregnancy. In both cases it is necessary to continue until
      the end of the week of 12. dosage should be individualized according to risk.

PMID- 24874829
TI  - [The use of synthetic mesh implants in surgical treatment of pelvic organ
      prolapse].
AB  - INTRODUCTION: Pelvic organ prolapse (POP) surgical treatment went through major
      changes thanks to availability and wider expansion of mesh implants (MI). This
      work is focused on critical analysis of outcomes of these surgical procedures and
      recommendation prescription for their uses in application pelvic surgery.
      METHODS: There was made analysis of published outcomes and experience with MI use
      in POP surgical treatment. OUTCOMES were analysed separately for each pelvic
      bottom section. Main criteria were surgical complications and treatment
      effectivity based on objective measurable parameters and subjective patients
      evaluation. OUTCOMES: There are formalized suitable indications and conditions
      for individual pelvic bottom sections for safe MI use in reconstructive POP
      surgery. On the basis of objective data authors also define specific situations
      when MI use doesn't bring any benefit and it is not recommended. CONCLUSION: Mesh
      implants have their definite place in POP surgical treatment. Implants with right
      indication and right surgical technique in comparison with classic surgical
      procedures have significantly lower recurrence risk with comparable or higher
      surgical complication rate.

PMID- 24874830
TI  - [New views on the functional morphology of human clitoris].
AB  - The clitoris is the female external sexual organ and is composed of erectile
      bodies. The distal portion of the vagina, clitoris and urethra form an integrated
      entity sui generis. All these components share a common vasculature and nerve
      supply and during sexual stimulation they respond as one functional unit. The
      clitoris is closely linked to the mechanism of sexual arousal in women. Glans has
      a dense network of receptors, innervated often with a several nerves at the same
      time - taking care of tactile sensitivity, thus, standing on the beginning of the
      journey, which culminates in orgasm. Nervus dorsalis clitoridis, which is a
      branch of n. pudendus, takes care of sensitive innervation. For blood supply is
      responsible a. clitoridis, which is a branch of a. pudenda interna. The most
      common congenital developmental anomalies of the clitoris include: clitoromegaly,
      penis-like clitoris and bifid clitoris. All, however, are among the relatively
      rare birth defects. Mechanism of orgasm gets attention between both laic and
      scientific community, although to this date there are speculations about its
      exact mechanism. There is relevant opinion, influenced by Freuds doctrine, which
      strictly recognizes two kinds of female orgasms - vaginal and clitoral, and,
      according to proponents of this theory, only the second mentioned is caused by
      stimulation of the clitoris. The second school unifies the term orgasm and claims
      that only clitoral stimulation (digital, penile, cunnilingus) and contraction of
      striated perineal muscle are responsible for orgasm, whether the glans (external
      part) or the body of the clitoris from the vaginal approach is stimulated.
      Therewithal, special term for mythical and still undocumented (despite many
      attempts and bold claims about its finding) G spot (named after Ernst Grafenberg,
      a German doctor who predicted the existence of this place) is redundant.
      Important role in the regulation of female sexuality and responsiveness play a
      hormonal influences and varying concentrations of neurotransmitters.

PMID- 24874831
TI  - [Guidlines for the good laboratory practice in assisted reproduction - clean
      environment].
AB  - The guidlines are the recommendation for good laboratory practice in
      embryological laboratories. In this first part the requirements of the clean
      environment from the point of view of the oocytes, sperm, and embryos protection
      against infection and from point of view of the embryological laboratory staff
      health protection were described.

PMID- 24874832
TI  - A small-scale anatomical dosimetry model of the liver.
AB  - Radionuclide therapy is a growing and promising approach for treating and
      prolonging the lives of patients with cancer. For therapies where high activities
      are administered, the liver can become a dose-limiting organ; often with a
      complex, non-uniform activity distribution and resulting non-uniform absorbed
      dose distribution. This paper therefore presents a small-scale dosimetry model
      for various source-target combinations within the human liver microarchitecture.
      Using Monte Carlo simulations, Medical Internal Radiation Dose formalism
      compatible specific absorbed fractions were calculated for monoenergetic
      electrons; photons; alpha particles; and (125)I, (90)Y, (211)At, (99m)Tc,
      (111)In, (177)Lu, (131)I and (18)F. S values and the ratio of local absorbed dose
      to the whole-organ average absorbed dose was calculated, enabling a
      transformation of dosimetry calculations from macro- to microstructure level. For
      heterogeneous activity distributions, for example uptake in Kupffer cells of
      radionuclides emitting low-energy electrons ((125)I) or high-LET alpha particles
      ((211)At) the target absorbed dose for the part of the space of Disse, closest to
      the source, was more than eight- and five-fold the average absorbed dose to the
      liver, respectively. With the increasing interest in radionuclide therapy of the
      liver, the presented model is an applicable tool for small-scale liver dosimetry
      in order to study detailed dose-effect relationships in the liver. 

PMID- 24874834
TI  - CSPG4-specific immunity and survival prolongation in dogs with oral malignant
      melanoma immunized with human CSPG4 DNA.
AB  - PURPOSE: Due to the many similarities with its human counterpart, canine
      malignant melanoma (cMM) is a valuable model in which to assess the efficacy of
      novel therapeutic strategies. The model is herein used to evaluate the
      immunogenicity, safety, and therapeutic efficacy of a human chondroitin sulfate
      proteoglycan-4 (hCSPG4) DNA-based vaccine. The fact that homology between hCSPG4
      and cCSPG4 amino-acidic sequences stands at more than 80% provides the rationale
      for using an hCSPG4 DNA vaccine in the cMM model. EXPERIMENTAL DESIGN: Dogs with
      stage II-III surgically resected CSPG4-positive oral MM were subjected to monthly
      intramuscular plasmid administration, which was followed immediately by
      electroporation (electrovaccination) for at least 6, and up to 20, months. The
      immunogenicity, safety, and therapeutic efficacy of the vaccine have been
      evaluated. RESULTS: hCSPG4 electrovaccination caused no clinically relevant local
      or systemic side effects and resulted in significantly longer overall and disease
      free survival times in 14 vaccinated dogs as compared with 13 nonvaccinated
      controls. All vaccinated dogs developed antibodies against both hCSPG4 and
      cCSPG4. Seven vaccinated dogs were also tested for a cCSPG4-specific T-cell
      response and only two gave a detectable interferon (IFN)gamma response.
      CONCLUSION: Xenogeneic electrovaccination against CSPG4 is able to overcome host
      unresponsiveness to the "self" antigen and seems to be effective in treating cMM,
      laying the foundation for its translation to a human clinical setting.

PMID- 24874833
TI  - Galeterone prevents androgen receptor binding to chromatin and enhances
      degradation of mutant androgen receptor.
AB  - PURPOSE: Galeterone inhibits the enzyme CYP17A1 and is currently in phase II
      clinical trials for castration-resistant prostate cancer (CRPC). Galeterone is
      also a direct androgen receptor (AR) antagonist and may enhance AR degradation.
      This study was undertaken to determine the molecular basis for AR effects and
      their therapeutic potential. EXPERIMENTAL DESIGN: Effects of galeterone on AR
      expression and activities were examined in prostate cancer cell lines. RESULTS:
      Similar to the AR antagonist enzalutamide, but in contrast to bicalutamide,
      galeterone did not induce binding of a constitutively active VP16-AR fusion
      protein to reporter genes and did not induce AR recruitment to endogenous
      androgen-regulated genes based on chromatin immunoprecipitation. Galeterone at
      low micromolar concentrations that did not induce cellular stress responses
      enhanced AR protein degradation in LNCaP and C4-2 cells, which express a T878A
      mutant AR, but not in prostate cancer cells expressing wild-type AR. Further
      transfection studies using stable LNCaP and PC3 cell lines ectopically expressing
      wild-type or T878A-mutant ARs confirmed that galeterone selectively enhances
      degradation of the T878A-mutant AR. CONCLUSIONS: Similar to enzalutamide,
      galeterone may be effective as a direct AR antagonist in CRPC. It may be
      particularly effective against prostate cancer cells with the T878A AR mutation
      but may also enhance degradation of wild-type AR in vivo through a combination of
      direct and indirect mechanisms. Finally, these findings show that conformational
      changes in AR can markedly enhance its degradation and thereby support efforts to
      develop further antagonists that enhance AR degradation.

PMID- 24874837
TI  - Terphenyl complexes of molybdenum and tungsten with quadruple metal-metal bonds
      and bridging carboxylate ligands.
AB  - Mono- and bis-terphenyl complexes of molybdenum and tungsten with general
      composition M2(Ar')(O2CR)3 and M2(Ar')2(O2CR)2, respectively (Ar' = terphenyl
      ligand), that contain carboxylate groups bridging the quadruply bonded metal
      atoms, have been prepared and structurally characterized. The new compounds stem
      from the reactions of the dimetal tetracarboxylates, M2(O2CR)4 (M = Mo, R = H,
      Me, CF3; M = W, R = CF3) with the lithium salts of the appropriate terphenyl
      groups (Ar' = Ar(Xyl2), Ar(Mes2), Ar(Dipp2), and Ar(Trip2)). Substitution of one
      bidentate carboxylate by a monodentate terphenyl forms a M-C sigma bond and
      creates a coordination unsaturation at the other metal atom. Hence in
      M2(Ar')2(O2CR)2 complexes the two metal atoms have formally a low coordination
      number and an also low electron count. However, the unsaturation seems to be
      compensated by a weak M-C(arene) bonding interaction that implicates one of the
      aryl substituents of the terphenyl central aryl ring, as revealed by X-ray
      studies performed with some of these complexes and by theoretical calculations.

PMID- 24874836
TI  - Avoiding complications in the repair of orbital floor fractures.
AB  - Fractures of the orbital floor are commonly repaired by all specialists who
      manage facial trauma. Potential complications include incomplete correction of
      preoperative enophthalmos or diplopia, as well as induction of hypoglobus or
      hyperglobus, eyelid malposition, or optic nerve injury. To optimize functional
      and aesthetic results, a stepwise analysis of the surgical procedure is presented
      from the election and timing of repair, through the incision and dissection path,
      release of herniated orbital tissue, implant material and placement, wound
      closure, and postoperative care. Key elements include the distinction of floor
      fracture subtypes, avoiding cicatricial contraction of the lower eyelid, complete
      release of herniated soft tissue, direct observation of all fracture margins, and
      proper contouring and positioning of the implant. 

PMID- 24874835
TI  - Squamous cell carcinoma of the oral tongue in young non-smokers is genomically
      similar to tumors in older smokers.
AB  - PURPOSE: Epidemiologic studies have identified an increasing incidence of
      squamous cell carcinoma of the oral tongue (SCCOT) in younger patients.
      EXPERIMENTAL DESIGN: DNA isolated from tongue tumors of young (<45 years, non
      smokers) and old (>45 years) patients at was subjected to whole-exome sequencing
      and copy-number analysis. These data were compared with data from similar
      patients in the TCGA (The Cancer Genome Atlas) project. RESULTS: In this study,
      we found that gene-specific mutation and copy-number alteration frequencies were
      similar between young and old patients with SCCOT in two independent cohorts.
      Likewise, the types of base changes observed in the young cohort were similar to
      those in the old cohort even though they differed in smoking history. TCGA data
      also demonstrate that the genomic effects of smoking are tumor site-specific, and
      we find that smoking has only a minor impact on the types of mutations observed
      in SCCOT. CONCLUSIONS: Overall, tumors from young patients with SCCOT appear
      genomically similar to those of older patients with SCCOT, and the cause for the
      increasing incidence of young SCCOT remains unknown. These data indicate that the
      functional impact of smoking on carcinogenesis in SCCOT is still poorly
      understood.

PMID- 24874838
TI  - Indomethacin promotes apoptosis in gastric cancer cells through concomitant
      degradation of Survivin and Aurora B kinase proteins.
AB  - Regular usage of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with
      reduced incidence of a variety of cancers. The molecular mechanisms underlying
      these chemopreventive effects remain poorly understood. This current
      investigation showed that in gastric cancer cells: (1) Indomethacin treatment
      enhanced the degradation of chromosomal passenger proteins, Survivin and Aurora B
      kinase; (2) Indomethacin treatment down-regulated Aurora B kinase activity in a
      cell cycle-independent fashion; (3) siRNA knockdown of Survivin level promoted
      Aurora B kinase protein degradation, and vice versa; (4) ectopic overexpression
      of Survivin blocked reduction of Aurora B kinase level and activity by
      indomethacin treatment, and vice versa; (5) siRNA knockdown of Aurora B kinase
      level and AZD1152 inhibition of its activity induced apoptosis, and
      overexpression of Aurora B kinase inhibited indomethacin-induced apoptosis; (6)
      indomethacin treatment reduced Aurora B kinase level, coinciding with reduction
      of Survivin level and induction of apoptosis, in KATO III and HT-29 cells, and in
      mouse gastric mucosa. A role for Aurora B kinase function in NSAID-induced
      apoptosis was not previously explored. Thus this report provides better
      understanding of the molecular mechanisms underlying the anti-cancer effect of
      NSAIDs by elucidating a significant role for Aurora B kinase in indomethacin
      induced apoptosis. 

PMID- 24874839
TI  - Integrin alpha E beta 7 (CD103) expression in bronchoalveolar lymphocytes of
      patients with hypersensitivity pneumonitis.
AB  - PURPOSE: CD4+/CD8+ ratio in bronchoalveolar lavage fluid (BALF) often retrieves
      contradictory findings when used for diagnosis of sarcoidosis and
      hypersensitivity pneumonitis (HP), so CD103+ has been investigated as a possible
      differential marker. We aimed to compare CD103+ expression in BALF T-lymphocytes
      between patients with HP, sarcoidosis and other interstitial lung diseases (ILD).
      METHODS: An observational study carried out over a 2-year period included
      consecutive patients with suspected ILD who underwent BALF as part of their
      initial diagnostic work-up; CD103+ expression on BALF T-lymphocytes was
      evaluated. After a final diagnosis established according to international
      criteria, three patient subgroups-HP, ILD (which included idiopathic interstitial
      pneumonia and connective tissue disease-associated lung disorders) and
      sarcoidosis-were considered for further analysis. RESULTS: A total of 77 subjects
      were enrolled, 20 with HP, 16 with other ILD and 41 with sarcoidosis. A
      significantly higher number of CD4+ CD103+ and CD8+ CD103+ lymphocytes were found
      in HP patients. Among patients with sarcoidosis, 12 (29.3 %) presented a BALF
      CD4+/CD8+ <3.5, all of them with histological confirmation. Compared to these
      patients, also statistically significant higher CD4+ CD103+ counts in HP patients
      were observed (p = 0.007). Among HP patients, although bird fanciers (n = 14)
      presented higher percentages of both CD4+ CD103+ and CD8+ CD103+ T-lymphocytes
      than those with work-related HP (n = 5), the differences did not reach
      statistical significance. CONCLUSIONS: Patients with HP present significantly
      higher counts of CD103+ T-lymphocytes in BALF, both in the CD4+ and CD8+ subsets,
      when compared to sarcoidosis, even with sarcoidosis subgroup presenting a BALF
      CD4+/CD8+ <3.5. The expression of CD103 may help in the interpretation of BALF
      data in these diffuse granulomatous lung disorders.

PMID- 24874840
TI  - Workload during cardiopulmonary resuscitation.
AB  - OBJECTIVES: Lay resuscitation is crucial for the survival of the patients with
      out-of-hospital cardiac arrest. Therefore, lay CPR should be a basic skill for
      everyone. With the growing proportion of retired people in the Western societies,
      CPR performed by people with preexisting diseases and at risk of cardiac events
      is expected to grow. There is little knowledge about the workload during CPR and
      the minimum workload capacity of the rescuer. METHODS: Pulse frequency, oxygen
      uptake, and CO2 elimination were measured by telemetry, while CPR was performed
      using a manikin with digital equipment for the standardization of the procedure.
      The same parameters were measured during a standard exercise testing protocol
      (spiroergometry) on a bicycle to analyze the aerobic endurance range of the
      participants. Data from the resuscitation protocols were correlated with those
      from spiroergometry to establish a simple standard investigation procedure to
      check people at risk and to give minimum requirements to perform CPR in Watts/kg.
      The study consisted of two parts: 1 (n = 16) explored minimal workload cutoffs
      for the rescuer using the 1995 recommendations and 2 (n = 14) tested the latest
      2010 guidelines to compare both recommendations. RESULTS: When tested according
      to the 1995 guidelines, heart frequency of rescuers increased from 83.0 bpm (+/
      11.3) at rest to 109.9 bpm (+/-12.6; P = 0.0004). The newer 2010 guidelines
      increased the workload marginally more (n.s.). CONCLUSION: CPR can be performed
      by healthy people within the range of aerobic endurance. The minimal requirements
      for trainings are 1.6-1.8 W/kg body weight in standard cycling ergometry. People
      at risk should be trained very careful. Since there is no significant lower
      workload when following the 1995 recommendations, people at risk should be
      trained according to the latest recommendations. In the case of a real
      resuscitation, such trained individuals must additionally take into account any
      symptoms.

PMID- 24874841
TI  - High scFv-receptor affinity does not enhance the antitumor activity of HER2
      retargeted measles virus.
AB  - The relationship between ligand-receptor affinity and antitumor potency of an
      oncolytic virus was investigated using a panel of six HER2/neu (HER2)-targeted
      measles viruses (MVs) displaying single-chain antibodies (scFv) that bind to the
      same epitope on HER2, but with affinities ranging from 10(-6) to 10(-11) M. All
      viruses were able to infect SKOV3ip.1 human ovarian cancer cells in vitro, but
      only the high-affinity MV (Kd>=10(-8) M) induced cytopathic effects of syncytia
      formation in the cell monolayers. In contrast, all six viruses were
      therapeutically active in vivo against orthotopic human ovarian SKOV3ip.1 tumor
      xenografts in athymic mice compared with saline-treated controls. The oncolytic
      activities of MV displaying the high-affinity scFv (Kd=10(-9), 10(-10), 10(-11)
      M) were not significantly superior to MV displaying scFv with Kd of 10(-8) M or
      less. Results from this study suggest that increasing the receptor affinity of
      the attachment protein of an oncolytic MV has minimal impact on its in vivo
      efficacy against a tumor that expresses the targeted receptor.

PMID- 24874842
TI  - Evaluation of apoptogenic adenovirus type 5 oncolytic vectors in a Syrian hamster
      head and neck cancer model.
AB  - Human adenovirus (HAdV) vectors are intensely investigated for virotherapy of a
      wide variety of human cancers. Here, we have evaluated the effect of two
      apoptogenic HAdV5 vectors in an immunocompetent Syrian hamster animal model of
      head and neck cancer. We established two cell lines of hamster cheek pouch
      squamous cell carcinomas, induced by treatment with 9,10-dimethyl-1,2
      benzanthracene. These cell lines, when infected with HAdV5 mutants lp11w and
      lp11w/Delta55 K (which are defective in the expression of either E1B-19 K alone
      or both E1B-19 K and E1B-55 K proteins) exhibited enhanced apoptotic and
      cytotoxic responses. The cheek pouch tumor cells transplanted either
      subcutaneously at the flanks or in the cheek pouches of hamsters readily formed
      tumors. Intratumoral administration of HAdV5-E1B mutants efficiently suppressed
      the growth of tumors at both sites. Histological examination of orthotopic tumors
      revealed reduced vascularity and the expression of the viral fiber antigen in
      virus-administered cheek pouch tumors. These tumors also exhibited increased
      caspase-3 levels, suggesting that virus-induced apoptosis may contribute to tumor
      growth suppression. Our results suggest that the apoptogenic HAdV5 vectors may
      have utility for the treatment of human head and neck cancers. 

PMID- 24874843
TI  - Akt-mediated transforming growth factor-beta1-induced epithelial-mesenchymal
      transition in cultured human esophageal squamous cancer cells.
AB  - Epithelial-mesenchymal transition (EMT) has a crucial role during embryonic
      development and has also come under intense scrutiny as a mechanism through which
      esophageal squamous cell cancer (ESCC) progresses to become metastatic.
      Transforming growth factor beta (TGF-beta)-mediated EMT has been observed in a
      variety of cell types and has been identified as the main inducer of EMT in many
      types of cancer. Akt activity is involved in TGF-beta-mediated EMT; however, its
      precise relationship and role in EMT in ESCC has not been well explained to date.
      Our data demonstrated that in human ESCC tissues Akt and its activated form,
      phosphorylated-Akt (p-Akt), were overexpressed; in addition, Akt and p-Akt were
      negatively correlated with epithelial cadherin (E-cadherin). In EC-9706 cells,
      exogenous TGF-beta1 could induce EMT and at the same time could increase the EC
      9706 cell invasive and metastatic ability. Moreover, Akt knockdown by small
      interfering RNA could attenuate the EMT induced by TGF-beta1 by increasing the
      epithelial marker E-cadherin and decreasing the mesenchymal marker Vimentin.
      Silencing Akt expression could decrease the migration ability of EC-9706 cells
      efficiently. In short, Akt is likely to have a more important role in the EMT
      induced by TGF-beta1 in EC-9706 and may contribute to the invasive and metastatic
      ability of EC-9706. Akt may be an effective therapeutic in advanced and
      metastatic ESCC. 

PMID- 24874844
TI  - Knockdown of cancerous inhibitor of protein phosphatase 2A may sensitize NSCLC
      cells to cisplatin.
AB  - Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a recently identified
      human oncoprotein that can stabilize some proteins by inhibiting degradation
      mediated by protein phosphatase 2A (PP2A) and it increases the proliferation of
      several cancer cells. Recent studies have highlighted a potential role for CIP2A
      in promoting tumor progression and metastasis. However, whether CIP2A could
      increase chemoresistance of cancer cells to chemotherapeutic agent cisplatin
      remains unclear. To determine whether CIP2A serves as a potential therapeutic
      target of human non-small-cell lung cancer (NSCLC), we utilized small
      interference RNA (siRNA) to knock down CIP2A expression in human NSCLC cells and
      analyzed their phenotypic changes. The data demonstrated that CIP2A silencing led
      to decreased proliferation, impaired clonogenicity and enhanced chemosensitivity
      and apoptosis to cisplatin in human NSCLC cells, as well as reduced Akt
      phosphorylation. In addition, overexpression of CIP2A diminished NSCLC cell
      chemosensitivity to cisplatin by inducing activation of Akt pathway, suggesting
      critical roles of CIP2A in NSCLC cell chemoresistance to cisplatin and rasing the
      possibility of CIP2A inhibition as a promising approach for lung cancer therapy. 

PMID- 24874846
TI  - H1N1 influenza vaccination during pregnancy.

PMID- 24874847
TI  - Axial contrast enhanced computed tomogram of the upper thorax.

PMID- 24874845
TI  - Evaluation of safety of A/H1N1 pandemic vaccination during pregnancy: cohort
      study.
AB  - OBJECTIVE: To assess the risk of maternal, fetal, and neonatal outcomes
      associated with the administration of an MF59 adjuvanted A/H1N1 vaccine during
      pregnancy. DESIGN: Historical cohort study. SETTING: Singleton pregnancies of the
      resident population of the Lombardy region of Italy. PARTICIPANTS: All deliveries
      between 1 October 2009 and 30 September 2010. Data on exposure to A/H1N1 pandemic
      vaccine, pregnancy, and birth outcomes were retrieved from regional databases.
      Vaccinated and non-vaccinated women were compared in a propensity score matched
      analysis to estimate risks of adverse outcomes. MAIN OUTCOME MEASURES: Main
      maternal outcomes included type of delivery, admission to intensive care unit,
      eclampsia, and gestational diabetes; fetal and neonatal outcomes included
      perinatal deaths, small for gestational age births, and congenital malformations.
      RESULTS: Among the 86,171 eligible pregnancies, 6246 women were vaccinated (3615
      (57.9%) in the third trimester and 2557 (40.9%) in the second trimester). No
      difference was observed in terms of spontaneous deliveries (adjusted odds ratio
      1.02, 95% confidence interval 0.96 to 1.08) or admissions to intensive care units
      (0.95, 0.47 to 1.88), whereas a limited increase in the prevalence of gestational
      diabetes (1.26, 1.04 to 1.53) and eclampsia (1.19, 1.04 to 1.39) was seen in
      vaccinated women. Rates of fetal and neonatal outcomes were similar in vaccinated
      and non-vaccinated women. A slight increase in congenital malformations, although
      not statistically significant, was present in the exposed cohort (1.14, 0.99 to
      1.31). CONCLUSIONS: Our findings add relevant information about the safety of the
      MF59 adjuvanted A/H1N1 vaccine in pregnancy. Residual confounding may partly
      explain the increased risk of some maternal outcomes. Meta-analysis of published
      studies should be conducted to further clarify the risk of infrequent outcomes,
      such as specific congenital malformations.

PMID- 24874848
TI  - Obesity rates rise substantially worldwide.

PMID- 24874849
TI  - Tobacco control policies should embrace harm reduction products, nicotine experts
      say.

PMID- 24874850
TI  - Guidelines based on multiple randomized studies prove the most durable, US study
      finds.

PMID- 24874853
TI  - Revisiting fixation and embedding techniques for optimal detection of dendritic
      cell subsets in tissues.
AB  - Organ-specific cell types are maintained by tissue homeostasis and may vary in
      nature and/or frequency in pathological situations. Moreover, within a cell
      lineage, some sub-populations, defined by combinations of cell-surface markers,
      may have specific functions. Dendritic cells are the epitome of such a population
      as they may be subdivided into discrete sub-groups with defined functions in
      specific compartments of various organs. Technically, to study the distribution
      of DC sub-populations, it involves performing multiparametric immunofluorescence
      on well-conserved organ structures. However, immunodetection may be impacted by
      protein cross-linking and antigenic epitope masking by the use of 10% neutral
      buffered formalin. To circumvent this and to preserve a good morphological tissue
      structure, we evaluated alternative fixatives such as Periodate Lysine
      Paraformaldehyde or Tris Zinc fixatives in combination with other embedding
      techniques. The cryosection protocols were adapted for optimal antigen detection
      but offered a poor morphological preservation. We therefore developed a new
      methodology based on Tris Zinc fixative, gelatin-sucrose embedding and freezing.
      Using multiple DC markers, we demonstrate that this treatment is an optimal
      protocol for cell-surface marker detection on high-quality tissue sections. 

PMID- 24874851
TI  - Poly (ADP-ribose) in the pathogenesis of Parkinson's disease.
AB  - The defining feature of Parkinson's disease is a progressive and selective demise
      of dopaminergic neurons. A recent report on Parkinson's disease animal model
      demonstrates that poly (ADP-ribose) (PAR) dependent cell death, also named
      parthanatos, is accountable for selective dopaminergic neuronal loss. Parthanatos
      is a programmed necrotic cell death, characterized by PARP1 activation, apoptosis
      inducing factor (AIF) nuclear translocation, and large scale DNA fragmentation.
      Besides cell death regulation via interaction with AIF, PAR molecule mediates
      diverse cellular processes including genomic stability, cell division,
      transcription, epigenetic regulation, and stress granule formation. In this
      review, we will discuss the roles of PARP1 activation and PAR molecules in the
      pathological processes of Parkinson's disease. Potential interaction between PAR
      molecule and Parkinson's disease protein interactome are briefly introduced.
      Finally, we suggest promising points of therapeutic intervention in the
      pathological PAR signaling cascade to halt progression in Parkinson's disease.

PMID- 24874856
TI  - Developmental changes of putreanine in vertebrate brains.
AB  - A method for the determination of putreanine has been developed, based on the
      separation of ion pairs with octanesulfonic acid on a reversed phase column. The
      method has been used to determine the developmental pattern of this amino acid in
      chick and rat brain. 

PMID- 24874852
TI  - Human selenium binding protein-1 (hSP56) is a negative regulator of HIF-1alpha
      and suppresses the malignant characteristics of prostate cancer cells.
AB  - In the present study, we demonstrate that ectopic expression of 56-kDa human
      selenium binding protein-1 (hSP56) in PC-3 cells that do not normally express
      hSP56 results in a marked inhibition of cell growth in vitro and in vivo. Down
      regulation of hSP56 in LNCaP cells that normally express hSP56 results in
      enhanced anchorage-independent growth. PC-3 cells expressing hSP56 exhibit a
      significant reduction of hypoxia inducible protein (HIF)-1alpha protein levels
      under hypoxic conditions without altering HIF-1alpha mRNA (HIF1A) levels. Taken
      together, our findings strongly suggest that hSP56 plays a critical role in
      prostate cells by mechanisms including negative regulation of HIF-1alpha, thus
      identifying hSP56 as a candidate anti-oncogene product.

PMID- 24874855
TI  - Cell proliferation in the embryonic mouse neocortex following acute maternal
      alcohol intoxication.
AB  - Experiments were conducted to examine the effects of 'binge' or acute maternal
      alcohol intoxication during the early proliferative phase of embryonic brain
      development. Primiparous mice received ethanol as 0, 10, 15 or 20% (v/v) aqueous
      solutions by gavage on days 13, 14 and 15 of gestation. Mean daily doses were
      0.0, 2.58, 4.03 and 5.40 ml/kg, respectively. There was no alcohol-related
      reduction in fetal body weight, length or fixed brain weight. Coronal sections (1
      MUm) of the dorsal roof of the lateral ventricles over the optic chiasma were
      examined from nine embryonic day 15 brains for each treatment group. The
      ventricular surface index of mitotic figures, the number and distribution of non
      surface mitotic figures, and the depth of the cortical roof and its constituent
      layers were determined. There was no alcohol-related difference in any of these
      parameters. These results are in contrast to those of a previous experiment using
      the same mouse strain, in which prolonged or chronic maternal alcohol consumption
      in the drinking water from days 11 to 19 of pregnancy was associated with a
      reduction in the surface index, a reduction in the depth of the cortical roof and
      an increase in the non-surface mitotic figures. These latter changes, however,
      occurred in the presence of reduced body weight. Our observations suggest that
      during this particular developmental period (corresponding to the second
      trimester of human pregnancy) alcohol-related reductions in brain growth parallel
      restrictions in general body growth. 

PMID- 24874854
TI  - Patient-centered care and distal radius fracture outcomes: a prospective cohort
      study analysis.
AB  - STUDY DESIGN: Prospective cohort. INTRODUCTION: Effects of patient-centered care
      on distal radius fracture recovery lacks evidence. PURPOSE OF THE STUDY: To
      understand from the perspective of a patient with a distal radius fracture: if
      the Patient Perception of Patient-Centeredness Questionnaire (PPPC) subscales
      apply to distal radius fracture populations; the strongest and weakest areas of
      patient-centered care; changes in patient perceptions of patient-centeredness
      during recovery; and, correlations between aspects of patient-centered care and
      patient reported pain and disability. METHODS: Patients with distal radius
      fractures (n = 129; mean age = 54.03, SD = 14.63) completed the Patient Rated
      Wrist Evaluation (PRWE) and PPPC, at baseline (less than 10 days post-fracture)
      and at three months post-injury. Outcome measure responses were factor analyzed
      and tested for correlations. RESULTS: Factors identified were titled Clinician
      Patient Dialogue, representing communication components of patient-centered care,
      and Clinician-Patient Alliance, representing partnership components of patient
      centered care. Small significant correlations (r = 0.22) between PRWE and PPPC
      responses were observed with Clinician-Patient Alliance more correlated at
      baseline and Clinician-Patient Dialogue at follow-up. DISCUSSION: Important
      aspects of the patient-clinician dynamic were identified. CONCLUSIONS:
      Communication between clinician and patient was perceived most favorably at
      baseline; and partnership improved by three months. LEVEL OF EVIDENCE: 1b.

PMID- 24874857
TI  - New formation of sensory cells in the tuberous organ (Electroreceptor) of
      Brienomyrus niger (Mormyridae) induced by transection of afferent nerve.
AB  - The tuberous organs-cutaneous electroreceptors of the mormyrid fish Brienomyrus
      niger-were examined, with the light and electron microscope, after sectioning of
      the afferent nerve of the lateral line. Transection of the afferent nerve leads
      to the concomitant complete degeneration of all sensory cells, and to a
      differentiation of new sensory cells from accessory cells, which constitute the
      platform. Ultrastructural examination of the newly formed sensory cells shows
      that within a few days these gain the characteristics of normal sensory cells.
      The rapidly growing cytoplasm is enclosed in a folded membrane; the foldings
      develop typical dense microvilli. At the same time, in spite of lack of
      innervation, synaptic bars surrounded by vesicles differentiate in the cytoplasm;
      these are opposed to the basal cell membrane which is attached to the accessory
      cell platform. The newly formed sensory cells never reach the size of normally
      developed sensory cells. Their existence is transitory, for they degenerate,
      together with the sensory cells, one month after de-afferentiation. 

PMID- 24874858
TI  - Membrane acetylcholinesterase in murine muscular dystrophy In vivo and in
      cultured myotubes.
AB  - Murine muscular dystrophy is characterized by a reduction of the 10S molecular
      form of acetylcholinesterase (AChE); this reduction occurs in both strains of
      dystrophic mice and at the time of the phenotypic appearance of the disease. In
      the present study we have analyzed the biochemical features, the cellular
      distribution and the developmental appearance of the AChE alteration. Sequential
      extractions with low salt, detergent and high salt revealed that this alteration
      affects only membrane-bound forms (those requiring Triton X-100 for
      solubilization), while both the low salt soluble and the high salt soluble forms
      appeared almost identical in normal and dystrophic muscles. Specific activity,
      sensitivity to different ions, pH dependence and Km were found to be identical in
      the enzymes from normal and dystrophic muscles, suggesting that the catalytic
      site of the 10S form is probably not altered. Further analysis, by non-denaturing
      gel electrophoresis, of the detergent soluble forms separated by sedimentation,
      revealed a single band for the 4S, a doublet for the 6S and three bands for the
      10S peaks, indicating the existence of charge heterogeneity in AChE molecular
      forms. The corresponding molecular forms from dystrophic muscles behaved
      identically upon electrophoresis: the residual activity in the detergent soluble
      10S form could still be separated into three bands, comigrating with their normal
      counterparts. Neuraminidase treatment resulted in a reduction of migration of
      both the 6S and 10S derived bands, but not of the 4S species, showing that sialic
      acid is added only to polymeric forms. Interestingly, the reduction of the 10S
      form appears to be linked to a developmental stage not reached in cell cultures,
      as cultured myotubes from muscles of dystrophic mice contained normal amounts of
      membrane-bound AChE forms. The molecular mechanism underlying the reduction of
      the tetrameric membrane bound AChE form in dystrophic muscle and the possible
      functional consequences are discussed. 

PMID- 24874859
TI  - The effect of exogenous gangliosides on neurons in culture: A morphometric
      analysis.
AB  - Cultures of isolated neurons have been treated with a purified preparation of
      gangliosides (10(-5)M and 10(-9)M) added to the cell growth medium at the 3rd day
      in culture and a morphometric analysis of the cells was performed with an image
      analyzer after 1 and 4 days of treatment. The number of cells and the area of the
      cell bodies were increased following the treatment. The results indicate as well
      the 'sprouting' effect of the glycolipids on the number of secondary neuronal
      processes and an increase in the length of the primary neuntes. The present data
      and other biochemical evidence (Dreyfus et al., 1984, J. Neurosci. Res.) suggest
      that the addition of exogenous gangliosides may have a trophic effect on neurons,
      greatly enhances the number of cell to cell contacts, and, possibly, stimulates
      cell proliferation and differentiation. 

PMID- 24874860
TI  - The postnatal development of glial fibrillary acidic protein and neurofilament
      triplet proteins in rat brain stem.
AB  - Cytoskeletal preparations containing both the glial fibrillary acidic protein and
      the neurofilament triplet proteins were prepared from brain stems of rats at
      different ages and the individual peptides separated in polyacrylamide gels.
      Stained peptide bands were quantitated as the area under peaks generated by
      densitometric scanning. Peak areas were converted to grams of protein based on
      total gel dye binding and total protein applied to the gels. Between 5 and 30
      days, the concentration of the peptide (g of peptide/mg of tissue protein) of
      apparent molecular weight 51,000 (corresponding to the glial fibrillary acidic
      protein), increased 3 fold. The corresponding increase in total concentration of
      the three peptides corresponding to the neurofilament proteins was 4.5 fold.
      However, the increase in concentration of the individual neurofilament peptides
      was each different. Very little of the apparent molecular weight 210,000
      neurofilament peptide was present at 5 days and its concentration increased 11
      fold by 30 days compared to about 3.5 fold for the other two neurofilament
      peptides. These results are in general agreement with studies using immunological
      techniques and the methods have the advantages of using readily available
      techniques and allowing the simultaneous comparison of both neuronal and glial
      specific filaments during development. 

PMID- 24874861
TI  - Microtubules and neurofilaments in the sciatic nerve fibres of the developing
      rat: Effects of thyroid deficiency.
AB  - Microtubules and neurofilaments were counted in cross-sections of the sciatic
      nerve fibres of young rats at various stages of development. A linear
      relationship was found between the numbers of microtubules and neurofilaments and
      the size of the fibre. The number of microtubules progressively increased during
      the first two postnatal weeks. Neurofilaments appeared slightly later than
      microtubules. In thyroid deficiency, the number of microtubules was diminished.
      The number of neurofilaments was not markedly affected. The ratio of
      neurofilaments to microtubules was thus increased. The severe retardation of
      sciatic nerve growth observed in thyroid deficiency might be related to the
      reduced number of microtubules and to a diminution in fibre plasticity induced by
      the higher neurofilament to microtubule ratio. 

PMID- 24874862
TI  - Postnatal development of glutamate metabolizing enzymes in hippocampus from mice.
AB  - The specific activity profiles of the glutamate synthesizing enzymes, phosphate
      activated glutaminase (EC 3.5.1.2), aspartate aminotransferase (EC 2.6.1.1),
      glutamate dehydrogenase (EC 1.4.1.2) and ornithine aminotransferase (EC 2.6.1.13)
      have been followed postnatally for 28 days in mouse hippocampus and compared to
      corresponding profiles in cerebellum and cerebral cortex (cf. refs 10 and 18).
      Phosphate activated glutaminase and glutamate dehydrogenase showed activity
      patterns similar to those found for cerebellum and glutamatergic granula cells
      cultured from cerebellum, whereas the aspartate aminotransferase activity pattern
      was found to be more similar to that previously observed for cerebral cortex as
      well as cultured cerebral interneurons which are likely to be GABAergic. The
      specific activity of ornithine aminotransferase was essentially unaltered during
      postnatal development, which is similar to what has been found for cerebellum and
      cerebral cortex. 

PMID- 24874863
TI  - Transient expression of neurofilament protein without filament formation in
      purkinje cell development Immunohistological and electron microscopic study of
      chicken cerebellum.
AB  - Purkinje cell bodies and dendrites in the chick embryo stained intensely by
      immunofluorescence and by the Avidin-Biotin Complex (ABC) method using monoclonal
      and polyclonal antibodies to the neurofilament (NF) proteins. On day 20 (the day
      before hatching) NF immunoreactivity markedly decreased concomitant with the
      first appearance of NF-positive basket axons in the molecular and Purkinje cell
      layers. On postnatal day 3, as in mature avian cerebellum, NF-negative Purkinje
      cells were surrounded by NF-positive baskets. Cytoplasmic 10 nm filaments were
      not observed in immature and mature Purkinje cells by electron microscopy. Basket
      axons in the hen were packed with 10 nm filaments. 

PMID- 24874864
TI  - Distribution of pipecolic acid and proline in the developing rat brain and
      peripheral organs.
AB  - The regional distribution of pipecolic acid and proline was studied in the adult
      and newborn rat brain. The brain concentration of pipecolic acid in the 1 and 3
      day-old rat was 6-10 times higher than in the adult. The brain concentration of
      proline was found to be about 3 times higher in the brain of a newborn rat than
      in the adult, then it gradually decreased during the period of lactation. In
      plasma as well as in peripheral tissues, such as heart, kidney and liver, the
      highest concentration of pipecolic acid was observed at 1 day and in the adult.
      Secretion of pipecolic acid into the urine was highest at early stages of
      development. In the gastrointestinal tract, pipecolic acid was found to be most
      abundant in the adult, whereas low levels were found during the period of
      lactation. The developmental and regional changes in concentration of proline
      were quite different from those of pipecolic acid. Our results suggest that the
      contribution of dietary pipecolic acid in building up levels of pipecolic acid in
      rat brain is small. 

PMID- 24874865
TI  - Neurofilament immunoreactivity in developing rat autonomic and sensory ganglia.
AB  - Immunoreactivity to neurofilament (NF) antiserum appears early in the development
      of both the central and peripheral nervous systems of the rat fetus. In 10 somite
      embryos, positive cell bodies are present in the ventromedial part of anterior
      rhombencephalic and mesencephalic neural tube. From there the appearance of
      immunoreactivity spreads cranially to the prosencephalic anlage before closure of
      the anterior neuropore and caudally following the sequence of neural tube
      closure. Immunoreactivity increases rapidly in axon bundles of central and
      peripheral systems, but in immature cell bodies of sensory ganglia the NF
      material only forms a ring around the nucleus. At 16 days of gestation, some cell
      bodies are progressively loaded with NF-immunoreactive material as a thick
      perinuclear network first and then in more excentrically located aggregates. This
      category of neurons is mainly observed in the distal part of the trigeminal
      ganglion, in petrous and nodose ganglia and in cervical dorsal root ganglia. In
      adult ganglia large cell bodies and some small ones present high NF
      immunoreactivity. In autonomic cell bodies (in superior cervical ganglion and in
      parasympathetic cranial ganglia) the immunoreactive material only forms a
      perinuclear ring slowly transformed into a loose perinuciear meshwork at the end
      of gestation. Intensely reactive nerve fibers are observed in cranial sensory as
      well as in sympathetic and parasympathetic ganglia and nerves. No positive cell
      bodies and only a few NF-immunoreactive nerves are observed in the carotid
      bodies. The NF immunoreactivity is better visualized on sections of fresh frozen
      material, treated with acetone, than in fixed specimens. These results are
      compared to previous observations reported for other species and for developing
      dorsal root ganglia. This immunostaining may be used to detect differentiation of
      peripheral sensory and autonomic neurons under experimental conditions. The
      uneven distribution of NF immunoreactivity in sensory neurons from stage 16 days
      of gestation as specific for precise subpopulations of neurons is discussed. 

PMID- 24874866
TI  - The trophic effect of gaba on cerebellar granule cells is mediated by gaba
      receptors.
AB  - The effect of GABA, its agonist THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3
      ol), and its antagonist bicuculline methobromide on the ultrastructure of
      cerebellar granule cells was studied. It was found that while the density of
      mitochondria, the ribosomes and smooth endoplasmic reticulum was unaffected by
      this treatment the density of neurotubules, rough endoplasmic reticulum, Golgi
      apparatus and coated as well as other vesicles was greatly enhanced by treatment
      of the cultured neurons with GABA (50 MUM) or THIP (150 MUM). The effects of GABA
      could be completely blocked by the simultaneous presence of bicuculline
      methobromide (150 MUM) in the culture media. The findings strongly suggest that
      the trophic action of GABA is mediated by GABA receptors and not by an
      intracellular action of GABA. 

PMID- 24874867
TI  - Mitogen-activated protein kinase 4 is a salicylic acid-independent regulator of
      growth but not of photosynthesis in Arabidopsis.
AB  - Mitogen-activated protein kinase (MAPK) pathways regulate signal transduction
      from different cellular compartments and from the extracellular environment to
      the nucleus in all eukaryotes. One of the best-characterized MAPKs in Arabidopsis
      thaliana is MPK4, which was shown to be a negative regulator of systemic-acquired
      resistance. The mpk4 mutant accumulates salicylic acid (SA), possesses
      constitutive expression of pathogenesis-related (PR) genes, and has an extremely
      dwarf phenotype. We show that suppression of SA and phylloquinone synthesis in
      chloroplasts by knocking down the ICS1 gene (by crossing it with the ics1 mutant)
      in the mpk4 mutant background did not revert mpk4-impaired growth. However, it
      did cause changes in the photosynthetic apparatus and severely impaired the
      quantum yield of photosystem II. Transmission microscopy analysis revealed that
      the chloroplasts' structure was strongly altered in the mpk4 and mpk4/ics1 double
      mutant. Analysis of reactive oxygen species (ROS)-scavenging enzymes expression
      showed that suppression of SA and phylloquinone synthesis in the chloroplasts of
      the mpk4 mutant caused imbalances in ROS homeostasis which were more pronounced
      in mpk4/ics1 than in mpk4. Taken together, the presented results strongly suggest
      that MPK4 is an ROS/hormonal rheostat hub that negatively, in an SA-dependent
      manner, regulates immune defenses, but at the same time positively regulates
      photosynthesis, ROS metabolism, and growth. Therefore, we concluded that MPK4 is
      a complex regulator of chloroplastic retrograde signaling for photosynthesis,
      growth, and immune defenses in Arabidopsis. 

PMID- 24874868
TI  - T-DNA-induced chromosomal translocations in feronia and anxur2 mutants reveal
      implications for the mechanism of collapsed pollen due to chromosomal
      rearrangements.

PMID- 24874869
TI  - Identification of target genes and transcription factors implicated in
      translation-dependent retrograde signaling in Arabidopsis.
AB  - Changes in organellar gene expression (OGE) trigger retrograde signaling. The
      molecular dissection of OGE-dependent retrograde signaling based on analyses of
      mutants with altered OGE is complicated by compensatory responses that mask the
      primary signaling defect and by secondary effects that influence other retrograde
      signaling pathways. Therefore, to identify the earliest effects of altered OGE on
      nuclear transcript accumulation, we have induced OGE defects in adult plants by
      ethanol-dependent repression of PRORS1, which encodes a prolyl-tRNA synthetase
      located in chloroplasts and mitochondria. After 32h of PRORS1 repression, the
      translational capacity of chloroplasts was reduced, and this effect subsequently
      intensified, while basic photosynthetic parameters were still unchanged at 51h.
      Analysis of changes in whole-genome transcriptomes during exposure to ethanol
      revealed that induced PRORS1 silencing affects the expression of 1020 genes in
      all. Some of these encode photosynthesis-related proteins, including several down
      regulated light-harvesting chlorophyll a/b binding (LHC) proteins. Interestingly,
      genes for presumptive endoplasmic reticulum proteins are transiently up
      regulated. Furthermore, several NAC-domain-containing proteins are among the
      transcription factors regulated. Candidate cis-acting elements which may
      coordinate the transcriptional co-regulation of genes sets include both G-box
      variants and sequence motifs with no similarity to known plant cis-elements. 

PMID- 24874870
TI  - Reduced dependence of Crested Ibis on winter-flooded rice fields: implications
      for their conservation.
AB  - The Crested Ibis Nipponia nippon was once thought to be extinct in the wild until
      seven birds were discovered in a remote mountain village in China in 1981.
      Studies suggested that winter-flooded rice fields play an essential role in nest
      site selection by the Crested Ibis and hence in their survival. Considerable
      efforts were therefore made to conserve the winter-flooded rice fields, but these
      have caused conflicts between the agricultural and conservation communities. The
      population and geographical range of the wild Crested Ibis has expanded greatly
      since 1981, but there is no spatial information on the winter-flooded rice
      fields, nor on the current association of nest sites and winter-flooded rice
      fields. We mapped winter-flooded rice fields across the entire current range of
      Crested Ibis using innovative remote sensing and geographical information systems
      (GIS) techniques. The spatial relationships between the nest site clusters and
      winter-flooded rice fields were quantified using Ward's hierarchical clustering
      method and Ripley's K-function. We show that both have significantly clumped
      distribution patterns and that they are positively associated. However, the
      dependence of Crested Ibis on the winter-flooded rice fields varied significantly
      among the nest site clusters and has decreased over the years, indicating the
      absence of winter-flooded rice fields is not constraining their recovery and
      population expansion. We therefore recommend that efforts should be made to
      protect the existing winter-flooded rice fields and to restore the functionality
      of natural and semi-natural wetlands, to encourage both in-situ conservation and
      the re-introduction of the Crested Ibis. In addition, we recommend that caution
      should be exercised when interpreting the habitat requirements of species with a
      narrow distribution, particularly when that interpretation is based only on their
      current habitat. 

PMID- 24874872
TI  - Beryllium-free Li4Sr(BO3)2 for deep-ultraviolet nonlinear optical applications.
AB  - Nonlinear optical (NLO) materials are of great importance in laser science and
      technology, as they can expand the wavelength range provided by common laser
      sources. Few NLO materials, except KBe2BO3F2 (KBBF), can practically generate
      deep-ultraviolet coherent light by direct second-harmonic generation process,
      limited by the fundamental requirements on the structure-directing optical
      properties. However, KBBF suffers a strong layering tendency and high toxicity of
      the containing beryllium, which hinder the commercial availability of KBBF. Here
      we report a new beryllium-free borate, Li4Sr(BO3)2, which preserves the
      structural merits of KBBF, resulting in the desirable optical properties.
      Furthermore, Li4Sr(BO3)2 mitigates the layering tendency greatly and enhances the
      efficiency of second-harmonic generation by more than half that of KBBF. These
      results suggest that Li4Sr(BO3)2 is an attractive candidate for the next
      generation of deep-ultraviolet NLO materials. This beryllium-free borate
      represents a new research direction in the development of deep-ultraviolet NLO
      materials. 

PMID- 24874871
TI  - Coordinating the cytoskeleton and endocytosis for regulated plasma membrane
      growth in the early Drosophila embryo.
AB  - Plasma membrane organization is under the control of cytoskeletal networks and
      endocytic mechanisms, and a growing literature is showing how closely these
      influences are interconnected. Here, we review how plasma membranes are formed
      around individual nuclei of the syncytial Drosophila embryo. Specifically, we
      outline the pathways that promote and maintain the growth of pseudocleavage and
      cellularization furrows, as well as specific pathways that keep furrow growth in
      check. This system has become important for studies of actin regulators, such as
      Rho1, Diaphanous, non-muscle myosin II and Arp2/3, and endocytic regulators, such
      as a cytohesin Arf-GEF (Steppke), clathrin, Amphiphysin and dynamin. More
      generally, it provides a model for understanding how cytoskeletal-endocytic cross
      talk regulates the assembly of a cell. 

PMID- 24874874
TI  - Microaerobic digestion of sewage sludge on an industrial-pilot scale: the
      efficiency of biogas desulphurisation under different configurations and the
      impact of O2 on the microbial communities.
AB  - Biogas produced in an industrial-pilot scale sewage sludge reactor (5m(3)) was
      desulphurised by imposing microaerobic conditions. The H2S concentration removal
      efficiency was evaluated under various configurations: different mixing methods
      and O2 injection points. Biogas was entirely desulphurised under all the
      configurations set, while the O2 demand of the digester decreased over time.
      Although the H2S removal seemed to occur in the headspace, S(0) (which was found
      to be the main oxidation product) was scarcely deposited there in the headspace.
      O2 did not have a significant impact on the digestion performance; the VS removal
      remained around 47%. Conversely, DGGE revealed that the higher O2 transfer rate
      to the sludge maintained by biogas recirculation increased the microbial richness
      and evenness, and caused an important shift in the structure of the bacterial and
      the archaeal communities in the long term. All the archaeal genera identified
      (Methanosaeta, Methanospirillum and Methanoculleus) were present under both
      anaerobic and microaerobic conditions.

PMID- 24874875
TI  - Comparison of steam gasification reactivity of algal and lignocellulosic biomass:
      influence of inorganic elements.
AB  - This study aims at comparing the steam gasification behaviour of two species of
      algal biomass (Chlamydomonas reinhardtii and Arthrospira platensis) and three
      species of lignocellulosic biomass (miscanthus, beech and wheat straw).
      Isothermal experiments were carried out in a thermobalance under chemical regime.
      Samples had very different contents in inorganic elements, which resulted in
      different reactivities, with about a factor of 5 between samples. For biomasses
      with ratio between potassium content and phosphorus and silicon content K/(Si+P)
      higher than one, the reaction rate was constant during most of the reaction and
      then slightly increased at high conversion. On the contrary, for biomasses with
      ratio K/(Si+P) lower than one, the reaction rate decreased along conversion. A
      simple kinetic model was proposed to predict these behaviours.

PMID- 24874873
TI  - Ethanol production from non-detoxified whole slurry of sulfite-pretreated empty
      fruit bunches at a low cellulase loading.
AB  - Sulfite pretreatment to overcome the recalcitrance of lignocelluloses (SPORL) was
      applied to an empty fruit bunches (EFB) for ethanol production. SPORL facilitated
      delignification through lignin sulfonation and dissolution of xylan to result in
      a highly digestible substrate. The pretreated whole slurry was enzymatically
      saccharified at a solids loading of 18% using a relatively low cellulase loading
      of 15 FPU/g glucan and simultaneously fermented without detoxification using
      Saccharomyces cerevisiae of YRH400. An ethanol yield of 217 L/tonne EFB was
      achieved at titer of 32 g/L. Compared with literature studies, SPORL produced
      high ethanol yield and titer with much lower cellulase loading without
      detoxification.

PMID- 24874877
TI  - Operational stability of naringinase PVA lens-shaped microparticles in batch
      stirred reactors and mini packed bed reactors-one step closer to industry.
AB  - The immobilization of naringinase in PVA lens-shaped particles, a cheap and
      biocompatible hydrogel was shown to provide an effective biocatalyst for naringin
      hydrolysis, an appealing reaction in the food and pharmaceutical industries. The
      present work addresses the operational stability and scale-up of the
      bioconversion system, in various types of reactors, namely shaken microtiter
      plates (volume ? 2 mL), batch stirred tank reactors (volume <400 mL) and a packed
      bed reactor (PBR, 6.8 mL). Consecutive batch runs were performed with the
      shaken/stirred vessels, with reproducible and encouraging results, related to
      operational stability. The PBR was used to establish the feasibility for
      continuous operation, running continuously for 54 days at 45 degrees C. The
      biocatalyst activity remained constant for 40 days of continuous operation. The
      averaged specific productivity was 9.07 mmol h(-1) g enzyme(-1) and the half-life
      of 48 days.

PMID- 24874876
TI  - Biodiversity and succession of microbial community in a multi-habitat membrane
      bioreactor.
AB  - The present study focused on establishing a multi-habitat membrane bioreactor, as
      well as exploring its biodiversity and succession of microbial communities. In a
      long-term operational period (100 days), the dissolved oxygen level of a local
      zone within the bioreactor decreased consistently from the original oxic state to
      the final anaerobic state, which led to a continuous succession of the microbial
      community in the bioreactor. The results revealed that the biodiversity of the
      microbial community in different zones simultaneously increased, with a similar
      microbial composition in their final successional stage. The results also
      indicated that the dominant species during the whole operation were distributed
      among 6 major phyla. At the initial operational stages, the dominant species in
      the anoxic-anaerobic and the oxic zones exhibited distinguished difference,
      whereas at the final operational stage, both zones presented nearly the same
      dominant microbial species and a rather similar structure in their microbial
      communities.

PMID- 24874878
TI  - Denitrifying sulfide removal by enriched microbial consortium: kinetic diagram.
AB  - Denitrifying sulfide removal (DSR) process simultaneously removes nitrate,
      sulfide and organic matters in the same reactor. This study isolated eight DSR
      strains and composed a microbial consortium to reveal the stoichiometry and
      kinetics of autotrophic, heterotrophic and mixotrophic denitrification (DSR). A
      novel kinetic diagram based on mass and electron balances was proposed to
      graphically interpret the system kinetics and identify the accessible regime
      where DSR reactions can be applied. Demonstration of the use of the proposed
      diagram showed the easy assessment of DSR system performance by the status on the
      diagram. 

PMID- 24874879
TI  - Facile pulping of lignocellulosic biomass using choline acetate.
AB  - Treating ground bagasse or Southern yellow pine in the biodegradable ionic liquid
      (IL), choline acetate ([Cho][OAc]), at 100 degrees C for 24h led to dissolution
      of hemicellulose and lignin, while leaving the cellulose pulp undissolved, with a
      54.3% (bagasse) or 34.3% (pine) reduction in lignin content. The IL solution of
      the dissolved biopolymers can be separated from the undissolved particles either
      by addition of water (20 wt% of IL) followed by filtration or by centrifugation.
      Hemicellulose (19.0 wt% of original bagasse, 10.2 wt% of original pine,
      containing 14-18 wt% lignin) and lignin (5.0 wt% of original bagasse, 6.0 wt% of
      original pine) could be subsequently precipitated. The pulp obtained from
      [Cho][OAc] treatment can be rapidly dissolved in 1-ethyl-3-methylimidazolium
      acetate (e.g., 17 h for raw bagasse vs. 7h for pulp), and precipitated as
      cellulose-rich material (CRM) with a lower lignin content (e.g., 23.6% for raw
      bagasse vs. 10.6% for CRM).

PMID- 24874880
TI  - Altered behavior in mice with deletion of the alpha2-antiplasmin gene.
AB  - BACKGROUND: The alpha2-antiplasmin (alpha2AP) protein is known to be a principal
      physiological inhibitor of plasmin, and is expressed in various part of the
      brain, including the hippocampus, cortex, hypothalamus and cerebellum, thus
      suggesting a potential role for alpha2AP in brain functions. However, the
      involvement of alpha2AP in brain functions is currently unclear. OBJECTIVES: The
      goal of this study was to investigate the effects of the deletion of the alpha2AP
      gene on the behavior of mice. METHODS: The motor function was examined by the
      wire hang test and rotarod test. To evaluate the cognitive function, a repeated
      rotarod test, Y-maze test, Morris water maze test, passive or shuttle avoidance
      test and fear conditioning test were performed. An open field test, dark/light
      transition test or tail suspension test was performed to determine the
      involvement of alpha2AP in anxiety or depression-like behavior. RESULTS AND
      CONCLUSIONS: The alpha2AP knockout (alpha2AP-/-) mice exhibited impaired motor
      function compared with alpha2AP+/+ mice. The alpha2AP-/- mice also exhibited
      impairments in motor learning, working memory, spatial memory and fear
      conditioning memory. Furthermore, the deletion of alpha2AP induced anxiety-like
      behavior, and caused an anti-depression-like effect in tail suspension.
      Therefore, our findings suggest that alpha2AP is a crucial mediator of motor
      function, cognitive function, anxiety-like behavior and depression-like behavior,
      providing new insights into the role of alpha2AP in the brain functions.

PMID- 24874881
TI  - The proper splicing of RNAi factors is critical for pericentric heterochromatin
      assembly in fission yeast.
AB  - Heterochromatin preferentially assembles at repetitive DNA elements, playing
      roles in transcriptional silencing, recombination suppression, and chromosome
      segregation. The RNAi machinery is required for heterochromatin assembly in a
      diverse range of organisms. In fission yeast, RNA splicing factors are also
      required for pericentric heterochromatin assembly, and a prevailing model is that
      splicing factors provide a platform for siRNA generation independently of their
      splicing activity. Here, by screening the fission yeast deletion library, we
      discovered four novel splicing factors that are required for pericentric
      heterochromatin assembly. Sequencing total cellular RNAs from the strongest of
      these mutants, cwf14Delta, showed intron retention in mRNAs of several RNAi
      factors. Moreover, introducing cDNA versions of RNAi factors significantly
      restored pericentric heterochromatin in splicing mutants. We also found that
      mutations of splicing factors resulted in defective telomeric heterochromatin
      assembly and mis-splicing the mRNA of shelterin component Tpz1, and that
      replacement of tpz1+ with its cDNA partially rescued heterochromatin defects at
      telomeres in splicing mutants. Thus, proper splicing of RNAi and shelterin
      factors contributes to heterochromatin assembly at pericentric regions and
      telomeres.

PMID- 24874883
TI  - Sterile insects to enhance agricultural development: the case of sustainable
      tsetse eradication on Unguja Island, Zanzibar, using an area-wide integrated pest
      management approach.

PMID- 24874882
TI  - Prevalence of unprotected anal intercourse among men who have sex with men in
      China: an updated meta-analysis.
AB  - OBJECTIVE: The purpose of this review was to assess the prevalence of unprotected
      anal intercourse (UAI) among men who have sex with men (MSM) in China. METHODS: A
      comprehensive search was conducted including online databases like "Wanfang",
      Chinese National Knowledge Infrastructure, PubMed and manual searches. Analyses
      using random-effects models were performed to estimate the prevalence of UAI
      among MSM in China. RESULTS: Sixty-two articles reporting eighty-two studies were
      selected. The pooled prevalence rates of UAI with any male partner, with regular
      male partners, with non-regular male partners, with casual male partners, and
      with commercial male partners among MSM were 53%(95%CI: 51-56%), 45%(95%CI: 39
      51%), 34%(95%CI: 24-45%), 33%(95%CI: 30-36%), 12% (95%CI: 5-26%), respectively. A
      cumulative meta-analysis found that the pooled UAI prevalence decreased over
      time. CONCLUSIONS: Although the prevalence of UAI with male partners among MSM in
      China presents a decreasing trend over the past decade, the concomitant rise in
      HIV prevalence and incidence indicates that current prevention intervention
      efforts are insufficient to effectively contain the spread of HIV. Therefore, the
      persistently high prevalence of risky sexual behaviors underscores the need for
      innovative and effective prevention strategies among MSM.

PMID- 24874884
TI  - Time of acquisition and network stability in pediatric resting-state functional
      magnetic resonance imaging.
AB  - Resting-state functional magnetic resonance imaging (rs-fMRI) has been shown to
      elucidate reliable patterns of brain networks in both children and adults.
      Studies in adults have shown that rs-fMRI acquisition times of ~5 to 6 min
      provide adequate sampling to produce stable spatial maps of a number of different
      brain networks. However, it is unclear whether the acquisition time directly
      translates to studies of children. While there are many similarities between the
      brains of children and adults, many differences are also evident. Children have
      increased metabolism, differences in brain morphology and connectivity strengths,
      greater brain plasticity, and increased brain noise. Furthermore, there are
      differences in physiologic parameters, such as heart and respiratory rates, and
      compliance of the blood vessels. These developmental differences could translate
      into different acquisition times for rs-fMRI studies in pediatric populations.
      Longer scan times, however, increase the subject burden and the risk for greater
      movement, especially in children. Thus, the goal of this study was to assess the
      optimum acquisition time of rs-fMRI to extract stable brain networks in school
      age children. We utilized fuzzy set theory in 84 six-to-eight year-old children
      and found that eight networks, including the default mode, salience, frontal,
      left frontoparietal, right frontoparietal, sensorimotor, auditory, and visual
      networks, all stabilized after ~51/2 min. The sensorimotor network showed the
      least stability, whereas the salience and auditory networks showed the greatest
      stability. A secondary analysis using dual regression confirmed these results. In
      conclusion, in young children with little head motion, rs-fMRI acquisition times
      of ~51/2 min can extract the full complement of brain networks.

PMID- 24874885
TI  - The Prevalence of Clinical and Electrocardiographic Risk Factors of
      Cardiovascular Death Among On-duty Professional Firefighters.
AB  - BACKGROUND: Firefighters have twice as many cardiovascular deaths as police
      officers and 4 times as many as emergency medical responders. The etiology for
      this high rate of mortality remains unknown. The electrocardiogram (ECG) is a
      widely used tool to screen populations at risk, yet there are no available on
      duty, high-resolution ECG recordings from firefighters. OBJECTIVE: We sought to
      evaluate the prevalence of clinical and ECG risk factors among on-duty
      professional firefighters during 12-lead ECG holter monitoring and exercise
      stress testing. METHODS: Firefighters were recruited from Surveying & Assessing
      Firefighters Fitness & Electrocardiogram (SAFFE) study. This descriptive study
      recruited firefighters from 7 firehouses across Upstate New York who completed on
      duty 24-hour Holter ECG monitoring and a standard exercise stress test. All
      analyses were completed by a reviewer blinded to all clinical data. RESULTS: A
      total of 112 firefighters (mean [SD] age, 44 [8] years; mostly white men)
      completed the study. Although all firefighters were in normal sinus rhythm, more
      than half of them had at least 1 high-risk ECG risk factor present, including
      abnormal sympathetic tone (elevated heart rate, 54%), abnormal repolarization
      (wide QRS-T angle, 25%), myocardial scarring (fragmented QRS, 24%), and
      myocardial ischemia (ST depression, 24%). Most firefighters tolerated the
      treadmill exercise stress test well (metabolic equivalent tasks, 11.8 + 2.5]);
      however, almost one-third had abnormal results of stress tests that required
      further evaluation to rule out subclinical coronary artery disease. CONCLUSIONS:
      Among on-duty professional firefighters, high-risk ECG markers of fatal cardiac
      events and abnormal stress test results that warrant further evaluation are
      prevalent. Annual physical checkups with routine 12-lead ECG can identify those
      who might benefit from preventive cardiovascular services.

PMID- 24874886
TI  - Development of a pharmacokinetic/pharmacodynamic/disease progression model in
      NC/Nga mice for development of novel anti-atopic dermatitis drugs.
AB  - 1. JHL45, a novel immune modulator against atopic dermatitis (AD), was
      synthesized from decursin isolated from Angelica gigas. The goal is to evaluate
      the lead compound using quantitative modeling approaches to novel anti-AD drug
      development. 2. We tested the anti-inflammatory effect of JHL45 by in vitro
      screening, characterized its in vitro pharmacokinetic (PK) properties. The dose
      dependent efficacy of JHL45 was developed using a
      pharmacokinetics/pharmacodynamics/disease progression (PK/PD/DIS) model in NC/Nga
      mice. 3. JHL45 has drug-like properties and pharmacological effects when
      administered orally to treat atopic dermatitis. The developed PK/PD/DIS model
      described well the rapid metabolism of JHL45, double-peak phenomenon in the PK of
      decursinol and inhibition of IgE generation by compounds in NC/Nga mice. Also, a
      quantitative model was developed and used to elucidate the complex interactions
      between serum IgE concentration and atopic dermatitis symptoms. 4. Our findings
      indicate that JHL45 has good physicochemical properties and powerful
      pharmacological effects when administered orally for treatment of AD in rodents.

PMID- 24874888
TI  - Growth inhibition of the cyanobacterium Microcystis aeruginosa and degradation of
      its microcystin toxins by the fungus Trichoderma citrinoviride.
AB  - Harmful cyanobacterial blooms are recognized as a rapidly expanding global
      problem that threatens human and ecosystem health. Many bacterial strains have
      been reported as possible agents for inhibiting and controlling these blooms.
      However, such algicidal activity is largely unexplored for fungi. In this study,
      a fungal strain kkuf-0955, isolated from decayed cyanobacterial bloom was tested
      for its capability to inhibit phytoplankton species in batch cultures. The strain
      was identified as Trichoderma citrinoviride Based on its morphological
      characteristics and DNA sequence. Microcystis aeruginosa co-cultivated with
      living fungal mycelia rapidly decreased after one day of incubation, and all
      cells completely died and lysed after 2 days. The fungal filtrate of 5-day
      culture also exhibited an inhibitory effect on M. aeruginosa, and this inhibition
      increased with the amount of filtrate and incubation time. Conversely, green
      algae and diatoms have not been influenced by either living fungal mycelia or
      culture filtrate. Interestingly, the fungus was not only able to inhibit
      Microcystis growth but also degraded microcystin produced by this cyanobacterium.
      The toxins were completely degraded within 5 days of incubation with living
      fungal mycelia, but not significantly changed with fungal filtrate. This fungus
      could be a potential bioagent to selectively control Microcystis blooms and
      degrade microcystin toxins.

PMID- 24874887
TI  - Severe ipsilateral musculoskeletal involvement in a Cornelia de Lange patient
      with a novel NIPBL mutation.
AB  - Cornelia de Lange Syndrome (CdLS) is a congenital autosomal dominant (NIPBL, SMC3
      and RAD21) or X-linked (SMC1A and HDAC8) disorder characterized by facial
      dysmorphism, pre and postnatal growth retardation, developmental delay and/or
      intellectual disability, and multiorgan involvement. Musculoskeletal
      malformations are usually bilateral and affect mainly the upper limbs; the range
      goes from brachyclinodactyly to severe reduction defects. Instead lower
      extremities are usually less and mildly involved. Here, we report on a 3-year-old
      Senegalese boy with typical craniofacial CdLS features, pre and postnatal growth
      retardation, atrial septal defect, developmental delay and right ipsilateral limb
      malformations, consistent with oligodactyly of the 3rd and 4th fingers, tibial
      agenesis and fibula hypoplasia. Exome sequencing and Sanger sequencing showed a
      novel missense mutation in NIPBL gene (c.6647A>G; p.(Tyr2216Cys)), which affects
      a conserved residue located within NIPBL HEAT repeat elements. Pyrosequencing
      analysis of NIPBL gene, disclosed similar levels of wild-type and mutated alleles
      in DNA and RNA samples from all tissues analyzed (oral mucosa epithelial cells,
      peripheral blood leukocytes and fibroblasts). These findings indicated the
      absence of somatic mosaicism, despite of the segmental asymmetry of the limbs,
      and confirmed biallelic expression for NIPBL transcripts, respectively.
      Additionally, conditions like Split-hand/foot malformation with long-bone
      deficiency secondary to duplication of BHLHA9 gene have been ruled out by the
      array-CGH and MLPA analysis. To our knowledge, this is the first CdLS patient
      described with major ipsilateral malformations of both the upper and lower
      extremities, that even though this finding could be due to a random event,
      expands the spectrum of limb reduction defects in CdLS. 

PMID- 24874889
TI  - Taiwan cobra phospholipase A2 suppresses ERK-mediated ADAM17 maturation, thus
      reducing secreted TNF-alpha production in human leukemia U937 cells.
AB  - The goal of this study was to explore the signaling pathway regulating the
      processing of proADAM17 into ADAM17 in Taiwan cobra phospholipase A2 (PLA2)
      treated human leukemia U937 cells. PLA2 induced reactive oxygen species (ROS)
      elicited p38 MAPK activation and ERK inactivation in U937 cells. Catalytically
      inactive bromophenacylated PLA2 (BPB-PLA2) and PLA2 mutants evoked Ca(2+)
      mediated p38 MAPK activation, and the level of phosphorylated ERK remained
      unchanged. PLA2 treatment reduced mature ADAM17 expression and secreted TNF-alpha
      (sTNF-alpha) production. Co-treatment of SB202190 (p38 MAPK inhibitor) and
      catalytically inactive PLA2 increased ERK phosphorylation, ADAM17 maturation and
      sTNF-alpha production. Nevertheless, mRNA levels of ADAM17 and TNF-alpha were
      insignificantly altered after PLA2 and SB202190/BPB-PLA2 treatment. ADAM17
      activity assay and knock-down of ADAM17 revealed that ADAM17 was involved in sTNF
      alpha production. Restoration of ERK activation increased the processing of
      proADAM17 into ADAM17 in PLA2-treated cells, while inactivation of ERK reduced
      ADAM17 maturation in untreated and SB202190/BPB-PLA2-treated cells. Removal of
      cell surface heparan sulfate abrogated PLA2 and SB202190/BPB-PLA2 effect on
      ADAM17 maturation. Taken together, the present data reveal that PLA2 suppresses
      ERK-mediated ADAM17 maturation, thus reducing sTNF-alpha production in U937
      cells. Moreover, the binding with heparan sulfate is crucial for the PLA2 effect.

PMID- 24874890
TI  - Bothropoides insularis venom cytotoxicity in renal tubular epithelia cells.
AB  - Bothropoides insularis (jararaca-ilhoa) is a native endemic snake limited to the
      specific region of Queimada Island, on Sao Paulo coast. Several local and
      systemic effects have been described due to envenomation caused by it, such as
      edema, tissue necrosis, hemorrhage and acute renal failure. Our previous studies
      have shown that Bothropoides insularis venom (BinsV) demonstrated important
      functional and morphologic alterations in rat isolated kidney, especially
      decrease in tubular electrolyte transport, osmotic clearance and tubular
      necrosis. In order to elucidate the direct nephrotoxicity mechanism, the aim of
      the present study was to investigate BinsV cytotoxicity effect on renal
      epithelial cells. The treatment with BinsV over MDCK culture decreased cell
      viability in all concentrations tested with IC50 of 9 MUg/mL. BinsV was able to
      induce membrane rupture and cell death with phosphatidilserine externalization.
      Furthermore, BinsV induced ROS overproduction and mitochondrial membrane
      potential collapse, as well as Bax translocation and caspases 3 and 7 expression.
      Therefore, these events might be responsible by BinsV-induced cell death caused
      by mitochondrial dysfunction and ROS overproduction in the direct cytotoxicity
      process. 

PMID- 24874891
TI  - Expeditious selective access to functionalized platforms of A(7)B-type
      heteroleptic lanthanide double-decker complexes of phthalocyanine.
AB  - A one-step method to access to functionalized heteroleptic lanthanide double
      decker complexes of phthalocyanine of A7B-type is reported. This optimized
      statistical method led to two hydroxylated model europium complexes, one of which
      was further converted into its mesylated and azido derivatives. 

PMID- 24874892
TI  - LCLUC as an entry point for transdisciplinary research--reflections from an
      agriculture land use change study in South Asia.
AB  - This article highlights applied understanding of classifying earth imaging data
      for land cover land use change (LCLUC) information. Compared to the many previous
      studies of LCLUC, the present study is innovative in that it applied geospatial
      data, tools and techniques for transdisciplinary research. It contributes to a
      wider discourse on practical decision making for multi-level governance.
      Undertaken as part of the BioDIVA project, the research adopted a multi-tiered
      methodical approach across three key dimensions: socioecology as the sphere of
      interest, a transdisciplinary approach as the disciplinary framework, and
      geospatial analysis as the applied methodology. The area of interest was the
      agroecosystem of Wayanad district in Kerala, India (South Asia). The methodology
      was structured to enable analysis of multi-scalar and multi-temporal data, using
      Wayanad as a case study. Three levels of analysis included: District (Landsat TM
      30m), Taluk or sub-district (ASTER-15m) and Village or Gram Panchayat (GeoEye
      0.5m). Our hypothesis, that analyzing patterns of land use change is pertinent
      for up-to-date assessment of agroecosystem resources and their wise management is
      supported by the outcome of the multi-tiered geospatial analysis. In addition,
      two examples from the project that highlight the adoption of LCLUC by different
      disciplinary experts are presented. A sociologist assessed the land ownership
      boundary for a selected tribal community. A faunal ecologist used it to assess
      the effect of landscape structure on arthropods and plant groups in rice fields.
      Furthermore, the Google Earth interface was used to support the overall
      validation process. Our key conclusion was that a multi-level understanding of
      the causes, effects, processes and mechanisms that govern agroecosystem
      transformation requires close attention to spatial, temporal and seasonal
      dynamics, for which the incorporation of local knowledge and participation of
      local communities is crucial.

PMID- 24874893
TI  - Long-term safety and efficacy of adalimumab in Japanese patients with moderate to
      severe Crohn's disease.
AB  - BACKGROUND AND AIMS: Adalimumab has been shown to be effective and well tolerated
      in patients with Crohn's disease. This analysis reports the results of a cohort
      of Japanese patients with moderate to severe Crohn's disease who were evaluated
      for up to 3years to assess the long-term use of adalimumab. METHODS: The study
      consisted of a double-blind part and an open-label part. Patients were included
      either in the 52-week double-blind, placebo-controlled part of the study followed
      by a 96-week open-label extension or in the open-label part from the beginning or
      in the event of a flare. Patients were treated with adalimumab and evaluated for
      up to 148weeks as 3 data cohorts: the all-adalimumab cohort (patients receiving
      >=1 injection of adalimumab), the 148-week follow-up subcohort (patients who
      completed 148weeks of follow-up after the first adalimumab dose), and the dose
      escalation subcohort (patients receiving adalimumab doses that increased to 80mg
      every other week). RESULTS: In the all-adalimumab cohort (n=79), clinical
      remission rates were approximately 30% after 36weeks of exposure to adalimumab
      and for the remainder of the study (35%, 33%, and 28% for weeks 48, 108, and 144,
      respectively). An improvement in quality of life was also maintained over the
      same period. In the dose-escalation subcohort (n=40), the clinical remission rate
      was 75% (6/8) 48weeks after dose escalation. Adalimumab was tolerated, and no
      deaths were reported. CONCLUSIONS: Adalimumab is effective for maintaining long
      term clinical remission in Japanese patients with moderate to severe Crohn's
      disease (NCT00445432).

PMID- 24874894
TI  - Hope and social support utilisation among different age groups of women with
      breast cancer and their spouses.
AB  - OBJECTIVE: Social support and hope are considered positive, important
      contributors to psychological well-being for women with breast cancer and their
      spouses. Few studies examine the role of age in relation to these variables. The
      current study compares the relationship between social support, hope and
      depression among different age groups of women with advanced breast cancer and
      their healthy spouses. DESIGN: Cross-sectional sample of 150 women with advanced
      breast cancer and their spouses. MAIN OUTCOME MEASURES: Social support, hope,
      depression and socio-demographic data. Analysis included comparison of these
      variables between groups of older and younger patients and their spouses.
      Structural equation modelling (SEM) was used to examine hope as a mediator of the
      relationship between social support and depression within each group (older and
      younger patients and spouses). RESULTS: Older patients and spouses reported lower
      levels of depression than younger ones. SEM showed that social support related
      directly to depression among younger women and older spouses, while hope was
      directly related to depression among older women and younger spouses and acted as
      a mediator between social support and depression. CONCLUSIONS: Theoretical,
      empirical and clinical implications regarding the understanding of the role of
      age in coping with cancer are discussed.

PMID- 24874895
TI  - Lead optimization of 1,4-azaindoles as antimycobacterial agents.
AB  - In a previous report, we described the discovery of 1,4-azaindoles, a chemical
      series with excellent in vitro and in vivo antimycobacterial potency through
      noncovalent inhibition of decaprenylphosphoryl-beta-d-ribose-2'-epimerase
      (DprE1). Nevertheless, high mouse metabolic turnover and phosphodiesterase 6
      (PDE6) off-target activity limited its advancement. Herein, we report lead
      optimization of this series, culminating in potent, metabolically stable
      compounds that have a robust pharmacokinetic profile without any PDE6 liability.
      Furthermore, we demonstrate efficacy for 1,4-azaindoles in a rat chronic TB
      infection model. We believe that compounds from the 1,4-azaindole series are
      suitable for in vivo combination and safety studies.

PMID- 24874896
TI  - Pros and cons of bifunctional platinum(IV) antitumor prodrugs: two are (not
      always) better than one.
AB  - This article evaluates the efficacy and applicability of bifunctional prodrugs
      consisting of a six-coordinate Pt(iv) octahedral core and one or more bioactive
      molecules. The platinum(iv) complexes release upon reduction the corresponding
      cytotoxic Pt(ii) agents and the bioactive molecules, able to inhibit some
      biochemical mechanisms of cancer growth and/or prevent the deactivation of the
      Pt(ii) metabolites. 

PMID- 24874898
TI  - Severe Breast Pain Resolved with Pectoral Muscle Massage.
AB  - Many mothers stop breastfeeding because of breast and/or nipple pain, despite
      recommendations by the World Health Organization to exclusively breastfeed for
      the first 6 months. Most commonly, such pain is thought to be caused by fungal or
      bacterial infection; however, many women do not respond to usual treatments for
      such diagnoses. Furthermore, there is much dispute in the literature about these
      diagnoses and treatments. We submit a series of 3 cases of mothers who presented
      with severe mastalgia (breast pain) and who did not respond to conventional
      treatments. After treating the patients with pectoral muscle massage and
      stretching, they each had complete resolution of their pain. We suggest that each
      of these mothers experienced constriction of the upper thoracic muscles on their
      mammary neurovasculature.

PMID- 24874897
TI  - Platelet aggregation and coagulation factors in orthopedic surgery.
AB  - Hemostasis is a major concern during the perioperative period. Changes in
      platelet aggregation and coagulation factors may contribute to the delicate
      balance between thrombosis and bleeding. We sought to better understand
      perioperative hemostasis by investigating the changes in platelet aggregation and
      coagulation factors during the perioperative period. We performed a prospective
      cohort analysis of 70 subjects undergoing non-emergent orthopedic surgery of the
      knee (n = 28), hip (n = 35), or spine (n = 7) between August 2011 and November
      2011. Plasma was collected preoperatively (T1), 1-h intraoperatively (T2), 1-h
      (T3), 24-h (T4) and 48-h (T5) postoperatively. Platelet function testing was
      performed using whole blood impedance aggregometry. Coagulation assays were
      performed for factor VII, factor VIII, von Willebrand Factor (vWF), and
      fibrinogen. Of the 70 patients, mean age was 64.1 +/- 9.8 years, 61% were female,
      and 74% were Caucasian. Platelet activity decreased until 1 h postoperatively and
      then significantly increased above baseline at 24- and 48-h postoperatively.
      Compared to baseline, coagulation factors decreased intraoperatively. Factor VII
      activity continued to decrease, while FVIII, vWF, and fibrinogen all increased
      above baseline postoperatively. The results of our study indicate significant
      changes in platelet activity and coagulation factors during the perioperative
      period. Both platelet activity and markers of coagulation decrease during the
      intraoperative period and then some increase postoperatively. These changes may
      contribute to the hypercoagulabity and/or bleeding risk that occurs in the
      perioperative period. Future prospective studies aimed at correlating hemostatic
      changes with perioperative outcomes are warranted.

PMID- 24874899
TI  - Anticoagulant therapy is prescribed less often in paroxysmal atrial fibrillation
      regardless of thromboembolic risk: results from the Registry of Atrial
      Fibrillation To Investigate New Guidelines (RAFTING).

PMID- 24874901
TI  - Acute heart failure due to pheochromocytoma crisis after levosulpiride
      administration.

PMID- 24874900
TI  - Mitral valve surgery for transient severe mitral regurgitation: an alternative to
      medical treatment?

PMID- 24874902
TI  - Ischemic, nonischemic, and probably "mixed" dilated cardiomyopathies: what's in a
      definition?

PMID- 24874903
TI  - An analog of Ac-SDKP improves heart functions after myocardial infarction by
      suppressing alternative activation (M2) of macrophages.

PMID- 24874904
TI  - Usefulness of risk grading system using albuminuria for predicting cardiovascular
      events and all-cause death in chronic kidney disease: a population-based
      prospective cohort study in Japan.

PMID- 24874905
TI  - Visfatin/Nampt induces telomere damage and senescence in human endothelial cells.

PMID- 24874907
TI  - Safety and efficacy of percutaneous transluminal pulmonary angioplasty in elderly
      patients.
AB  - BACKGROUND: Percutaneous transluminal pulmonary angioplasty (PTPA) is a recently
      developed catheter-based therapy for chronic thromboembolic pulmonary
      hypertension (CTEPH). The aim of the present study was to investigate the safety
      and efficacy of PTPA in elderly patients with CTEPH. METHODS: In all, 257 PTPA
      sessions in 70 patients (median age 63 years) were analyzed. Patients were
      divided into two groups according to age: (i) a younger group (<65 years; n=39);
      and (ii) an elderly group (>=65 years; n=31). RESULTS: Hemodynamic improvements
      were comparable between the younger and elderly groups (63.1% vs. 68.2% decrease
      in pulmonary vascular resistance, respectively; P>0.05). The median length of
      stay in the intensive care unit after each session (1.0 vs. 1.0 days) and in
      hospital per session (9.2 vs. 9.4 days) was similar between the two groups
      (P>0.05 for all). The prevalence of reperfusion pulmonary edema (23.4% vs. 26.3%
      across all sessions) and other complications, such as contrast dye-induced
      nephropathy (0% vs. 2.0%), infection (0% vs. 0%), and neurological complications
      (0% vs. 1.0%), was comparable in the younger vs. elderly groups (P>0.05 for all).
      One-year all-cause mortality was similar in the younger and elderly groups (0%
      vs. 3.2%, respectively; P>0.05). CONCLUSIONS: PTPA can be performed safely and
      effectively, even in elderly patients, and could be considered as an alternative
      therapeutic strategy for elderly patients who are too fragile for pulmonary
      endarterectomy (PEA) or who are treated in institutions without highly
      experienced PEA surgeons.

PMID- 24874906
TI  - Tracking of cardiovascular risk factors from childhood to young adulthood - the
      Pune Children's Study.

PMID- 24874908
TI  - Patient characteristics and comorbidities associated with cerebrovascular
      accident following acute myocardial infarction in the United States.
AB  - BACKGROUND: Although cerebrovascular accident (CVA) is a relatively infrequent
      complication of acute myocardial infarction (AMI), the occurrence of CVA in
      patients with AMI is associated with increased morbidity and mortality. We wanted
      to assess post-AMI CVA rate in the United States and identify the associated
      patient characteristics, comorbidities, type of AMI, and utilization of invasive
      procedures. METHODS: This is an observational study from the Nationwide Inpatient
      Sample, 2006-2008. Using multivariate regression models, we assessed predictive
      risk factors for post-AMI CVA among patients admitted for AMI. RESULTS: Among the
      1,924,413 patients admitted for AMI, the overall rate of CVA was 2% (ischemic
      stroke: 1.47%, transient ischemic attack [TIA]: 0.35% and hemorrhagic stroke:
      0.21%). In this sample of AMI patient, higher incidence of CVA was associated
      with: CHF (adjusted odds ratio [AOR] 1.71; 95% confidence interval [CI], 1.58
      1.84,), age over 65 AOR, 1.65; 95% CI, 1.60-1.70, alcohol abuse AOR, 1.60; 95%
      CI, 1.49-1.73, cocaine use AOR, 1.48; 95% CI, 1.29-1.70, atrial fibrillation AOR,
      1.43; 95% CI, 1.39-1.46, Black race AOR, 1.35; 95% CI, 1.30-1.40, female gender
      AOR, 1.32; 95% CI, 1.29-1.35, peripheral vascular disease [PVD] AOR, 1.26; 95%
      CI, 1.22-1.30, coronary artery bypass graft (CABG) AOR, 1.22; 95% CI, 1.17-1.27,
      P<0.0001, STEMI AOR, 1.17; 95% CI, 1.14-1.20 and teaching hospitals AOR, 1.09;
      95% CI, 1.06-1.12. CONCLUSION: Female gender, older age (age>=65), black
      ethnicity, comorbidities including CHF, PVD, atrial fibrillation as well as STEMI
      and undergoing CABG were associated with the highest risk of CVA post-AMI.

PMID- 24874909
TI  - The effect of a six-month resistance-type exercise training program on the course
      of high sensitive cardiac troponin T levels in (pre)frail elderly.

PMID- 24874910
TI  - Pulmonary vein isolation as a treatment for severe atrial functional mitral
      regurgitation in a patient with atrial fibrillation.

PMID- 24874912
TI  - Comparison of the longevity of implantable cardioverter-defibrillator devices by
      different manufacturers.

PMID- 24874911
TI  - A novel individualized substrate modification approach for the treatment of long
      standing persistent atrial fibrillation: preliminary results.
AB  - BACKGROUND: The most effective approach for long-standing persistent atrial
      fibrillation (LPAF) ablation remained undetermined. Our goal was to explore the
      heterogeneous left atrial substrate in patients with LPAF and to evaluate the
      effectiveness of a novel individualized substrate modification (ISM) approach in
      LPAF ablation. METHODS: One hundred and twenty-four patients with LPAF were
      randomized to ISM group (n=64) or stepwise ablation (SA) group (n=60). After
      pulmonary vein isolation, ISM was performed in the ISM group and SA was applied
      in the SA group. The clinical effectiveness after a single and a repeated
      procedure was compared. RESULTS: The total procedural time was significantly
      shorter in ISM than that in SA. In the ISM group, mild left atrial substrate was
      observed in 17 (27.4%), moderate in 26 (41.9%) and severe in 19 (30.6%) patients
      after successful cardioversion of the 62 patients. The intention-to-treat
      analysis showed that sinus rhythm was maintained in 65.5% of patients in the ISM
      group and in 45.0% of patients in the SA group after a single procedure, P=0.04.
      Atrial tachycardia (AT) recurred in 5 of 22 in the ISM group and in 20 of 33 in
      the SA group, P=0.01. After a repeated procedure, 75% of patients in the ISM
      group and 63.3% of patients in the SA group were free of further recurrence,
      P=0.16. CONCLUSIONS: Left atrial substrate varied noticeably in patients with
      LPAF. The ISM approach was superior to SA approach in terms of procedural time,
      recurrence rate of AT and clinical effectiveness after a single procedure.
      However, they yielded comparable outcomes after a repeated procedure.

PMID- 24874914
TI  - Organic soluble and uniform film forming oligoethylene glycol substituted BODIPY
      small molecules with improved hole mobility.
AB  - Judiciously chosen side chains of conjugated molecules have a positive impact on
      charge transport properties when used as the active material in organic
      electronic devices. Amongst the side chains, oligoethylene glycols (OEGs) have
      been relatively unexplored due to their hydrophilic nature. OEGs also affect the
      smooth film formation of conjugated molecules, which preclude device fabrication.
      However, X-ray diffraction studies have shown that OEGs facilitate intermolecular
      contact, which is a desirable property for the fabrication of organic electronic
      devices. Thus the challenge is to design and synthesize organic solvent soluble
      and uniform film forming conjugated molecules with OEG side chains. We have
      designed and synthesized conjugated small molecules (CSMs) comprising BODIPY as
      acceptor and triphenylamine as donor with an OEG side chain. This molecule forms
      smooth films when processed from organic solvents. In order to understand the
      impact of the OEG side chain, we have also synthesized alkyl chain analogs. All
      the molecules exhibit exactly the same HOMO and LUMO energy levels, but the
      packing in the solid state is different. CSM with methyl side chains exhibit an
      inter planar distance of 4.15 A. Contrary to this, the OEG side chain containing
      CSM showed an inter planar spacing of 4.30 A, which is 0.2 A less than the alkyl
      side chain comprising CSMs. Please note that the length of the hydrophobic and
      hydrophilic side chains is the same. Interestingly, the OEG side chain comprising
      CSM showed two orders of higher hole carrier mobilities compared to all the other
      derivatives. The same molecule also showed an extremely low threshold voltage of 
      0.27 V indicating the OEG side chains' favourable interaction between substrate
      as well as between molecules. 

PMID- 24874913
TI  - Comparison between mixed and central venous oxygen saturation in patients with
      severe acute heart failure after cardiac surgery: a prospective observational
      study.

PMID- 24874915
TI  - Assessing the effectiveness of problem-based learning of preventive medicine
      education in China.
AB  - Problem-based learning (PBL) is defined as a student-centered pedagogy which can
      provide learners more opportunities for application of knowledge acquired from
      basic science to the working situations than traditional lecture-based learning
      (LBL) method. In China, PBL is increasingly popular among preventive medicine
      educators, and multiple studies have investigated the effectiveness of PBL
      pedagogy in preventive medicine education. A pooled analysis based on 15 studies
      was performed to obtain an overall estimate of the effectiveness of PBL on
      learning outcomes of preventive medicine. Overall, PBL was associated with a
      significant increase in students' theoretical examination scores (SMD = 0.62, 95%
      CI = 0.41-0.83) than LBL. For the attitude- and skill-based outcomes, the pooled
      PBL effects were also significant among learning attitude (OR = 3.62, 95% CI =
      2.40-5.16), problem solved skill (OR = 4.80, 95% CI = 2.01-11.46), self-directed
      learning skill (OR = 5.81, 95% CI = 3.11-10.85), and collaborative skill (OR =
      4.21, 95% CI = 0.96-18.45). Sensitivity analysis showed that the exclusion of a
      single study did not influence the estimation. Our results suggest that PBL of
      preventive medicine education in China appears to be more effective than LBL in
      improving knowledge, attitude and skills. 

PMID- 24874917
TI  - Characterization of the house dust mite allergen Der p 21 produced in Pichia
      pastoris.
AB  - BACKGROUND: The development of recombinant house dust mite (HDM) allergens opened
      the way for the in-depth characterization of these molecules but also provided
      new opportunities to refine the diagnostic procedures of HDM allergy as well as
      the allergen-specific immunotherapy through tailor-made treatments. OBJECTIVE: In
      the present study, the HDM allergen Der p 21 was expressed in Pichia pastoris
      under a secreted form. The physico-chemical as well as the allergenic
      characterizations of recombinant Der p 21 (rDer p 21) were performed. METHODS:
      Purified rDer p 21, secreted from recombinant P. pastoris was characterized by CD
      and MS analysis and the frequency of IgE reactivity was determined by ELISA using
      96 sera of HDM-allergic patients from Bangkok. The direct airway epithelial cell
      activation by rDer p 21 was also evaluated. RESULTS: rDer p 21 was highly
      expressed under a secreted form in P. pastoris. The physico-chemical
      characterization of purified rDer p 21 showed that the allergen displayed
      appropriate alpha-helix secondary structure content although a two amino acids
      truncation at the N-terminus of the protein was evidenced by MS. The prevalence
      of IgE reactivity to rDer p 21 reached 25% in the cohort of the HDM-allergic
      patients. rDer p 21 could trigger IL-8 production in airway epithelial cells
      through TLR2-dependent signaling. CONCLUSION: Properly folded rDer p 21 produced
      in P. pastoris is appropriate for HDM allergy diagnosis as well for future
      recombinant allergen-based specific immunotherapy.

PMID- 24874916
TI  - Erythrocyte folate concentrations, CpG methylation at genomically imprinted
      domains, and birth weight in a multiethnic newborn cohort.
AB  - Epigenetic mechanisms are proposed to link maternal concentrations of methyl
      group donor nutrients with the risk of low birth weight. However, empirical data
      are lacking. We have examined the association between maternal folate and birth
      weight and assessed the mediating role of DNA methylation at nine differentially
      methylated regions (DMRs) of genomically imprinted genes in these associations.
      Compared with newborns of women with folate levels in the lowest quartile, birth
      weight was higher in newborns of mothers in the second (beta = 143.2, se = 63.2,
      P = 0.02), third (beta = 117.3, se = 64.0, P = 0.07), and fourth (beta = 133.9,
      se = 65.2, P = 0.04) quartiles, consistent with a threshold effect. This pattern
      of association did not vary by race/ethnicity but was more apparent in newborns
      of non-obese women. DNA methylation at the PLAGL1, SGCE, DLK1/MEG3 and IGF2/H19
      DMRs was associated with maternal folate levels and also birth weight, suggestive
      of threshold effects. MEG3 DMR methylation mediated the association between
      maternal folate levels and birth weight (P =0.06). While the small sample size
      and partial scope of examined DMRs limit our conclusions, our data suggest that,
      with respect to birth weight, no additional benefits may be derived from
      increased maternal folate concentrations, especially in non-obese women. These
      data also support epigenetic plasticity as a key mechanistic response to folate
      availability during early fetal development. 

PMID- 24874918
TI  - An intracellularly activatable, fluorogenic probe for cancer imaging.
AB  - A newly designed, dual-functional probe based on intracellular activation has
      been successfully developed for the detection of cancer cells. The probe is
      nearly non-fluorescent in buffer due to its highly efficient FRET quenching, but
      it can be specifically activated with dramatic fluorescence enhancement upon
      intracellular cathepsin B cleavage in target cancer cells after selective
      internalization via folate receptor-dependent endocytosis. Therefore, this probe
      enables "turn-on" visualization of cancer cells with desirable specificity and
      contrast enhancement. This targeted, intracellularly activatable probe exhibits
      low fluorescence-quenched background when compared with "always-on" probes and
      avoids non-specific activation by non-specifically expressed enzymes in normal
      tissue, which normally occurs when using common "turn on" probe design
      strategies. Therefore, this probe can be potentially applied in intraoperative
      inspection during clinical cancer surgery with higher contrast and sensitivity. 

PMID- 24874919
TI  - 5-HTTLPR/rs25531 polymorphism and neuroticism are linked by resting state
      functional connectivity of amygdala and fusiform gyrus.
AB  - The s/s-genotype of the 5-HTTLPR polymorphism and the personality trait of
      neuroticism have both been associated with experiences of negative affect,
      anxiety and mood disorders, as well as an emotional processing bias towards
      negative facial emotions. On a neural level, this bias can be characterized by
      altered amygdala and fusiform gyrus (FFG) activity during perception of negative
      facial expressions. Using resting-state functional magnetic resonance imaging in
      a multi-center-sample of 178 healthy subjects of European descent, this study
      investigated the association of 5-HTTLPR (short s- and long l-allele) including
      the genotype of the single nucleotide polymorphism (SNP) rs25531 (A/G) within
      this region polymorphism, and trait neuroticism on resting-state functional
      connectivity (rs-FC) between amygdala and the FFG. Moreover, we aimed to identify
      additional brain regions with associations of 5-HTTLPR/rs25531 (combined
      according to its expression; low: s/s; high: l(A)/l(A); intermediate: s/l(A),
      s/l(G), l(G)/l(G), l(A)/l(G)) and trait neuroticism to amygdala rs-FC. Separate
      analyses for 5-HTTLPR/rs25531 and neuroticism (controlling for age, gender,
      handedness, and research site) revealed that s/s-homozygotes and individuals high
      in neuroticism obtained altered amygdala rs-FC in the right occipital face area,
      which is considered to be a "core component" of the face processing system.
      Importantly, effects of neuroticism were replicated across three independent
      research sites. Additionally, associations of 5-HTTLPR/rs25531 genotype and
      amygdala rs-FC were observed in the anterior and posterior cingulate cortex,
      whereas neuroticism was not related to rs-FC in these areas. The presented data
      implies that 5-HTTLPR/rs25531 variants and neuroticism are linked by resting
      state functional connectivity of amygdala and fusiform gyrus and suggests that
      variants of 5-HTTLPR/rs25531 genotype and different levels of neuroticism may
      partly account for altered processing of negative facial emotions.

PMID- 24874920
TI  - Antagomirs targeting microRNA-134 increase hippocampal pyramidal neuron spine
      volume in vivo and protect against pilocarpine-induced status epilepticus.
AB  - Emerging data support roles for microRNA (miRNA) in the pathogenesis of various
      neurologic disorders including epilepsy. MicroRNA-134 (miR-134) is enriched in
      dendrites of hippocampal neurons, where it negatively regulates spine volume.
      Recent work identified upregulation of miR-134 in experimental and human
      epilepsy. Targeting miR-134 in vivo using antagomirs had potent anticonvulsant
      effects against kainic acid-induced seizures and was associated with a reduction
      in dendritic spine number. In the present study, we measured dendritic spine
      volume in mice injected with miR-134-targeting antagomirs and tested effects of
      the antagomirs on status epilepticus triggered by the cholinergic agonist
      pilocarpine. Morphometric analysis of over 6,400 dendritic spines in Lucifer
      yellow-injected CA3 pyramidal neurons revealed increased spine volume in mice
      given antagomirs compared to controls that received a scrambled sequence.
      Treatment of mice with miR-134 antagomirs did not alter performance in a
      behavioral test (novel object location). Status epilepticus induced by
      pilocarpine was associated with upregulation of miR-134 within the hippocampus of
      mice. Pretreatment of mice with miR-134 antagomirs reduced the proportion of
      animals that developed status epilepticus following pilocarpine and increased
      animal survival. In antagomir-treated mice that did develop status epilepticus,
      seizure onset was delayed and total seizure power was reduced. These studies
      provide in vivo evidence that miR-134 regulates spine volume in the hippocampus
      and validation of the seizure-suppressive effects of miR-134 antagomirs in a
      model with a different triggering mechanism, indicating broad conservation of
      anticonvulsant effects. 

PMID- 24874921
TI  - Cryptic species revealed by molecular phylogenetic analysis of sequences obtained
      from basidiomata of Tulasnella.
AB  - Delimitation of species and the search for a proper threshold for defining
      phylogenetic species in fungi are under discussion. In this study, morphological
      and molecular data are correlated to delimit species of Tulasnella, the most
      important mycobionts of Orchidaceae, which suffer from poor taxonomy. Resupinate
      basidiomata of Tulasnella species were collected in Ecuador and Germany, and 11
      specimens (seven from Ecuador, four from Germany) were assigned to traditional
      species concepts by use of morphological keys. The specimens were compared by
      micro-anatomical examination with 75 specimens of Tulasnella borrowed from
      fungaria to obtain better insights on variation of characters. Sequences of the
      ITS region (127) were obtained after cloning from the fresh basidiomata and from
      pure cultures. Proportional variability of ITS sequences was analyzed within and
      among the cultures and the specimens designated to different morphospecies.
      Results suggested an intragenomic variation of less than 2%, an intraspecific
      variation of up to 4% and an interspecific divergence of more than 9% in
      Tulasnella. Cryptic species in Tulasnella, mostly from Ecuador, were revealed by
      phylogenetic analyses with 4% intraspecific divergence as a minimum threshold for
      delimiting species. Conventional diagnostic morphological characters appeared
      insufficient for species characterization. Arguments are presented for molecular
      delimitation of the established species Tulasnella albida, T. asymmetrica, T.
      eichleriana, T. cf. pinicola, T. tomaculum and T. violea. 

PMID- 24874922
TI  - Heat- and light-induced detachment of the light harvesting complex from isolated
      photosystem I supercomplexes.
AB  - In a previous study, using photosystem I enriched stroma thylakoid membrane
      vesicles, we have shown that the light harvesting complexes of this photosystem
      are prone to heat- and light-induced, thermo-optically driven detachment from the
      supercomplex [43]. We have also shown that the splitting of the supercomplex
      occurs in a gradual and specific manner, selectively affecting the different
      constituents of the antenna complexes. Here we further analyse these heat- and
      light-induced processes in isolated Photosystem I supercomplex using circular
      dichroism and 77K fluorescence emission spectroscopy and immuno blotting, and
      obtain further details on the sequence of events of the dissociation process as
      well as on the thermal stability of the different components. Our absorption and
      circular dichroism spectroscopy and immuno blotting data show that the
      dissociation of LHCI from PSI-LHCI supercomplex starts above 50 degrees C. Also,
      the low temperature fluorescence emission spectra depicts decrease of maximum
      fluorescence emission at 730nm and an increase of the intensity at 685nm, and
      about 10nm blue-shifts, from 730 to 720nm and from 685 to 676nm, respectively,
      indicating the heat (50 degrees C) induced detachment of LHCI from PSI core
      complexes. The reaction centre proteins are highly stable even at high
      temperatures. Lhca2 is more heat stable than the other light harvesting protein
      complexes of PSI, whereas Lhca4 and Lhca3 are rather labile. Combined heat and
      light treatments significantly enhances the disorganization of PSI-LHCI
      supercomplexes, indicating a thermo-optic mechanism, which might have significant
      role under combined heat and light stress conditions. 

PMID- 24874923
TI  - A vesicular stomatitis virus-based mucosal vaccine promotes dendritic cell
      maturation and elicits preferable immune response against coxsackievirus B3
      induced viral myocarditis.
AB  - Recombinant vesicular stomatitis virus (VSV) is widely used as a vaccine
      platform. However, the capacity of VSV-based vaccines to induce mucosal immunity
      has not been fully investigated. In the present study, a recombinant VSV
      expressing coxsackievirus B3 (CVB3) major immunogen VP1 has been generated and
      the immune protection elicited by VSV-VP1 was evaluated. We demonstrated that
      intranasal delivery of VSV-VP1 can induce a potent antigen-specific mucosal
      immune response as well as a systemic immune response, particularly the induction
      of polyfunctional T cells. Importantly, mice immunized with VSV-VP1 were better
      protected against CVB3-induced viral myocarditis than those receiving a chitosan
      formulated DNA vaccine. Increased dendritic cell (DC) maturation in the
      mesenteric lymph node (MLN) was observed in the mice vaccinated with VSV-VP1,
      which could be a potential mechanism for the protective immune response. These
      findings support VSV as a viral delivery vector that can induce robust mucosal
      immunity that should be considered for further vaccine development. 

PMID- 24874924
TI  - Systematic analysis of the lysine acetylome in Vibrio parahemolyticus.
AB  - Lysine acetylation of proteins is a major post-translational modification that
      plays an important regulatory role in almost every aspect of cells, both
      eukaryotes and prokaryotes. Vibrio parahemolyticus, a model marine bacterium, is
      a worldwide cause of bacterial seafood-borne illness. Here, we conducted the
      first lysine acetylome in this bacterium through a combination of highly
      sensitive immune-affinity purification and high-resolution LC-MS/MS. Overall, we
      identified 1413 lysine acetylation sites in 656 proteins, which account for 13.6%
      of the total proteins in the cells; this is the highest ratio of acetyl proteins
      that has so far been identified in bacteria. The bioinformatics analysis of the
      acetylome showed that the acetylated proteins are involved in a wide range of
      cellular functions and exhibit diverse subcellular localizations. More
      specifically, proteins related to protein biosynthesis and carbon metabolism are
      the preferential targets of lysine acetylation. Moreover, two types of
      acetylation motifs, a lysine or arginine at the +4/+5 positions and a tyrosine,
      histidine, or phenylalanine at the +1/+2 positions, were revealed from the
      analysis of the acetylome. Additionally, protein interaction network analysis
      demonstrates that a wide range of interactions are modulated by protein
      acetylation. This study provides a significant beginning for the in-depth
      exploration of the physiological role of lysine acetylation in V.
      parahemolyticus. 

PMID- 24874927
TI  - Comparison of the substrate specificity of two ring-hydroxylating dioxygenases
      from Sphingomonas sp. VKM B-2434 to polycyclic aromatic hydrocarbons.
AB  - The genes of two ring-hydroxylating dioxygenases (RHDs) of Sphingomonas sp. VKM B
      2434 were cloned and expressed in Escherichia coli. The relative values of the
      RHD specificity constants were estimated for six polycyclic aromatic hydrocarbons
      (PAHs) based on the kinetics of PAH mixture conversion by the recombinant
      strains. The substrate specificity profiles of the enzymes were found to be very
      different. Dioxygenase ArhA was the most specific to acenaphthylene and showed a
      low specificity to fluoranthene. Dioxygenase PhnA was the most specific to
      anthracene and phenanthrene and showed a considerable specificity to
      fluoranthene. Knockout derivatives of Sphingomonas sp. VKM B-2434 lacking ArhA,
      PhnA, and both dioxygenases were constructed. PAH degradation by the single
      knockout mutants was in agreement with the substrate specificity of the RHD
      remaining intact. Double-knockout mutant lacking both enzymes was unable to
      oxidize PAHs. A mutant form of dioxygenase ArhA with altered substrate
      specificity was described.

PMID- 24874926
TI  - Continued decline of aqueous interleukin-8 after multiple intravitreal injections
      of ganciclovir for cytomegalovirus retinitis.
AB  - PURPOSE: To evaluate the relationship between aqueous inflammation cytokines and
      cytomegalovirus (CMV) particles in patients with cytomegalovirus retinitis
      (CMVR), and evaluate the changes in aqueous inflammation cytokines during
      multiple intravitreal injections of antiviral drugs for CMVR. METHODS: There were
      10 patients (12 eyes; 16 courses of treatment per eye) who underwent continued
      intravitreal ganciclovir or foscarnet for treatment of CMVR. Before each
      intravitreal injection, 50-100 MUL of aqueous humor was removed and sent to the
      laboratory to examine the concentration of the CMV DNA load by using polymerase
      chain reaction and to examine the concentration of interleukin (IL)-1beta, IL-6,
      IL-8, IL-10, tumor necrosis factor (TNF)-alpha, and IL-12p70 using a cytometric
      bead array. RESULTS: A Kendall correlation test showed that the concentration of
      the CMV DNA load in the aqueous humor was significantly associated with the
      aqueous level of IL-6 (P<0.001, r=0.327) and IL-8 (P<0.001, r=0.381), but not
      significantly associated with IL-1beta, IL-10, IL-12p70, and TNF-alpha. The
      boxplots showed that the concentration of the aqueous CMV DNA load, IL-8 and IL
      10 continuously declined after multiple intravitreal injections of antiviral
      drugs, and the decline trend of IL-8 was most remarkable. IL-1beta, IL-10, TNF
      alpha, and IL-12p70 were negative in some of the aqueous levels of CMVR patients
      throughout the course of treatment (25.0%-62.5%). CONCLUSIONS: Our study showed
      that IL-8 was significantly associated with the aqueous level of CMV copies and
      continuously declined during a course of treatment that involved multiple
      intravitreal injections of antiviral drugs. IL-8 may be considered a good
      quantitative laboratory indicator of the recovery of CMVR.

PMID- 24874925
TI  - KLF2--a negative regulator of pre-B cell clonal expansion and B cell activation.
AB  - Maturation as well as antigen-dependent activation of B cells is accompanied by
      alternating phases of proliferation and quiescence. We and others have previously
      shown that Kruppel-like factor 2 (KLF2), a regulator of T cell quiescence and
      migration, is upregulated in small resting precursor (pre)-B cells after assembly
      of the immature pre-B cell receptor (pre-BCR) and is downregulated upon antigen
      induced proliferation of mature B cells. These findings suggest that KLF2,
      besides its function in maintaining follicular B cell identity, peripheral B cell
      homeostasis and homing of antigen-specific plasma cells to the bone marrow, also
      controls clonal expansion phases in the B cell lineage. Here, we demonstrate that
      enforced expression of KLF2 in primary pre-B cells results in a severe block of
      pre-BCR-induced proliferation, upregulation of the cell cycle inhibitors p21 and
      p27 and downregulation of c-myc. Furthermore, retroviral KLF2 transduction of
      primary B cells impairs LPS-induced activation, favors apoptosis and results in
      reduced abundance of factors, such as AID, IRF4 and BLIMP1, that control the
      antigen-dependent phase of B cell activation and plasma cell differentiation.
      Hence, we conclude that KLF2 is not only a key player in terminating pre-B cell
      clonal expansion but also a potent suppressor of B cell activation. 

PMID- 24874928
TI  - Survival and prognostic factors in patients treated with stereotactic
      radiotherapy for brain metastases.
AB  - BACKGROUND: Stereotactic radiation therapy (SRT) of brain metastases is used with
      good effect around the world, but no consensus exists regarding which prognostic
      factors that are related to favourable or unfavourable prognosis after the
      treatment. A better definition of these factors will ensure a more precise
      application of the treatment. MATERIAL AND METHODS: A consecutive cohort of the
      198 patients treated for brain metastases with SRT without concurrent whole-brain
      radiation therapy at our department from 2001 to 2012 was retrospectively
      analysed. RESULTS: Median survival was seven months and median time to clinical
      cerebral progression was eight months. The multivariate analysis revealed age >=
      65 years, Performance Status >= 2, extracranial metastases and size of metastasis
      > 20 mm as independent prognostic factors related to shorter survival. No factors
      were independently related to clinical cerebral progression. CONCLUSION: We
      identified four prognostic factors related to survival after SRT for brain
      metastases. The grouping of patients by these factors is useful to determine the
      level of treatment. We discourage the delivery of SRT to patients with 3-4
      unfavourable prognostic factors because of the very short median survival of two
      months.

PMID- 24874929
TI  - Efflux pump ABCB1 single nucleotide polymorphisms and dose reductions in patients
      with metastatic renal cell carcinoma treated with sunitinib.
AB  - There is growing evidence that sunitinib plasma levels have an impact on
      treatment outcome in patients with metastatic renal cell carcinoma (mRCC). We
      studied the impact of single nucleotide polymorphisms (SNPs) in genes involved in
      sunitinib pharmacokinetics, and additionally, sunitinib pharmacodynamics on dose
      reductions of the tyrosine kinase inhibitor. METHODS: We retrospectively analyzed
      germ-line DNA retrieved from mRCC patients receiving sunitinib as first-line
      therapy. We genotyped 11 key SNPs, respectively, in ABCB1, NR1/2, NR1/3 and
      CYP3A5, involved in sunitinib pharmacokinetics as well as VEGFR1 and VEGFR3,
      which have been suggested as regulators of sunitinib pharmacodynamics.
      Association between these SNPs and time-to-dose-reduction (TTDR) was studied by
      Cox regression. RESULTS: We identified 96 patients who were treated with
      sunitinib and from whom germ-line DNA and data on dose reductions were available.
      We observed an increased TTDR in patients carrying the TT-genotype in ABCB1
      rs1125803 compared to patients with CC- or CT-genotypes (19 vs. 7 cycles; p =
      0.031 on univariate analysis and p = 0.012 on multivariate analysis) and an
      increased TTDR in patients carrying the TT/TA-variant in ABCB1 rs2032582 compared
      to patients with the GG- or GT/GA-variant (19 vs. 7 cycles; p = 0.046 on
      univariate analysis and p = 0.024 on multivariate analysis). CONCLUSION: mRCC
      patients carrying the rs1128503 TT-variant or the TT/TA-variant in rs2032582 in
      ABCB1, which encodes for an efflux pump, do require less dose reductions due to
      adverse events compared to patients with the wild type or heterozygote variants
      in these genes.

PMID- 24874930
TI  - Effects of a single dose of erythropoietin on motor function and cognition after
      focal brain ischemia in adult rats.
AB  - We tested the influence of erythropoietin (EPO), a basic cytokine in
      erythropoiesis regulation, on the process of motor function and cognition after
      focal brain ischemia induced by a local application of endothelin. Endothelin-1
      (ET-1) induced short lasting strong vasoconstriction, with described impact on
      the structure and on the function of neuronal cells. Neurological description of
      motor function and Morris water maze test (the swimming test is one of most
      widely used methods for studying cognitive functions in rodents) were used to
      study the process of learning and memory in three-month-old male albino Wistar
      rats (n=52). Both tests were performed one week before, and three weeks after
      ischemia induction (endothelin application on the cortex in the area of a.
      cerebri media dx.). Experimental group received i.p. injection of EPO (5,000
      IU/kg body weight, 10 min before endothelin application). Control group of
      animals received one i.p. injection of saline at the dose of 1 ml/kg body weight
      at the same time. Only sham surgery was performed in the third group of animals.
      Rats with EPO pretreatment before the experimental lesion exhibited significantly
      better motor and cognitive function then those with saline injection. No
      significant changes in the motor and cognitive function were found in the third
      group of rats (sham operated controls). 

PMID- 24874931
TI  - Are serum procalcitonin and interleukin-1 beta suitable markers for diagnosis of
      acute pyelonephritis in children?
AB  - Rapid diagnosis of acute pyelonephritis is important because of its association
      with long-standing complications. This study was conducted to compare the
      reliability of serum procalcitonin (PCT) and interleukin-1 beta (IL-1beta) with
      conventional laboratory parameters for diagnosis of acute pyelonephritis in
      children. Seventy nine children with urinary tract infection were divided into
      two groups based on the result of Tc-99m dimercaptosuccinic acid renal scan:
      acute pyelonephritis (n=33) and lower UTI (urinary tract infection) (n=46)
      groups. White blood cell (WBC) count, neutrophil count, erythrocyte sedimentation
      rate (ESR), serum C-reactive protein (CRP), PCT and IL-1beta concentrations of
      both groups were measured and compared. WBC count, neutrophil count, ESR, serum
      CRP, PCT and IL-1beta concentrations were higher in acute pyelonephritis patients
      than in the lower UTI group (P<0.05). The sensitivity and specificity of serum
      PCT and IL-1beta for diagnosis of acute pyelonephritis were 31, 84.7% and 27.2,
      90% respectively (using a cut-point value of 0.5 ng/ml for PCT and 6.9 pg/ml for
      IL-1beta). The sensitivity of PCT and IL-1beta for diagnosis of acute
      pyelonephritis was less than that of conventional markers such as ESR and CRP.
      This study revealed that serum PCT and IL-1beta are not good biologic markers for
      differentiating acute pyelonephritis from lower UTI. It seems that conventional
      inflammatory markers such as ESR and CRP besides the clinical findings are more
      reliable for the diagnosis of acute pyelonephritis in children. 

PMID- 24874932
TI  - Differential expression of inflammation-related genes after intense exercise.
AB  - The present study focused on the identification of the difference in expression
      of inflammation-related genes after intense exercise by oligonucleotide
      microarray methods. This may finally lead to an improved understanding of
      underlying cellular and molecular mechanism of the immunological alterations in
      response to exercises. The study group consisted of three healthy road cyclists.
      Peripheral blood mononuclear cells (PBMCs) were collected preexercise,
      immediately post-exercise and after 15 min of recovery. The analysis of the
      expression profile of genes related to the inflammation was performed in PBMCs
      using HG-U133A oligonucleotide microarrays. 4 genes were found to be regulated by
      more than 2.0-fold (IL1R2, IL2RB, IL8, IL8RB). Venn diagram indicated that only
      one of differentially expressed genes (TXLNA) remains the same in each
      comparison. The balance of both pro- and anti-inflammatory cytokines after
      exercise seems to be important for athletes. Optimal inflammatory and immune
      response may help optimize exercise regimes, link physical activity with health
      and diagnose or prevent athletes from overtraining. 

PMID- 24874933
TI  - A comparison between transcutaneous and total serum bilirubin in healthy-term
      greek neonates with clinical jaundice.
AB  - The accuracy of transcutaneous bilirubin meters has been assessed in newborns
      from various ethnic backgrounds. However, there are limited data on Greek
      newborns. Our study examined the accuracy of transcutaneous bilirubin
      measurements in clinically jaundiced healthy-term Greek newborns, using total
      serum bilirubin as the reference standard, in order to re-evaluate our local
      guidelines about neonatal jaundice. Clinically jaundiced newborns requiring total
      serum bilirubin level estimation were recruited prospectively. 368 pairs of total
      serum bilirubin/transcutaneous bilirubin measurements were taken in 222 newborns,
      using a direct spectrophotometric device and the BiliCheck device, respectively.
      The level of agreement between the obtained transcutaneous bilirubin and total
      serum bilirubin values was assessed. Our data were analysed using the Stata/SE
      12.0 (StataCorp LP, USA) statistical programme. The mean (+/- SD) TSB was 225.4
      +/- 25.4 MUmol/l and the mean (+/- SD) TcB was 237.9 +/- 21.0 MUmol/l. The
      correlation between the values was poor (Pearson's correlation coefficient 0.439;
      Lin's concordance coefficient 0.377 [95% CI 0.301 to 0.453]; P<0.001). The Bland
      Altman analysis demonstrated that transcutaneous bilirubin measurements tended to
      overestimate the total serum bilirubin value (mean difference 12.5 +/- 24.9
      MUmol/l), with wide 95% limits of agreement (-36.2 MUmol/l to 61.3 MUmol/l).
      Transcutaneous bilirubin values did not correlate well with total serum bilirubin
      values, being often imprecise in predicting the actual total serum bilirubin
      levels. This permits us to continue estimating total serum bilirubin in
      clinically jaundiced newborns according to our local guidelines, in order to
      safely decide the appropriate care plan. 

PMID- 24874934
TI  - Effect of amphetamine on adult male and female rats prenatally exposed to
      methamphetamine.
AB  - The aim of the present study was to examine the cross-sensitization induced by
      prenatal methamphetamine (MA) exposure to adult amphetamine (AMP) treatment in
      male and female rats. Rat mothers received a daily injection of MA (5 mg/kg) or
      saline throughout the gestation period. Adult male and female offspring
      (prenatally MA- or saline-exposed) were administered with AMP (5 mg/kg) or saline
      (1 ml/kg) in adulthood. Behaviour in unknown environment was examined in open
      field test (Laboras), active drug-seeking behaviour in conditioned place
      preference test (CPP), spatial memory in the Morris water maze (MWM), and levels
      of corticosterone (CORT) were analyzed by enzyme immunoassay (EIA). Our data
      demonstrate that in Laboras test, AMP treatment in adulthood increased general
      locomotion (time and distance travelled) regardless of the prenatal exposure and
      sex, while AMP increased exploratory activity (rearing) only in prenatally MA
      exposed animals. AMP induced sensitization only in male rats, but not in females
      when tested drug-seeking behaviour in the CPP test. In the spatial memory MWM
      test, AMP worsened the performance only in females, but not in males. On the
      other hand, males swam faster after chronic AMP treatment regardless of the
      prenatal drug exposure. EIA analysis of CORT levels demonstrated higher level in
      females in all measurement settings. In males, prenatal MA exposure and chronic
      adult AMP treatment decreased CORT levels. Thus, our data demonstrated that adult
      AMP treatment affects behaviour of adult rats, their spatial memory and stress
      response in sex-specific manner. The effect is also influenced by prenatal drug
      exposure. 

PMID- 24874935
TI  - How smoking cessation influence hormonal levels in postmenopausal women?
AB  - Smoking represents the most widespread substance dependence in the world.
      Nicotine alters women hormonal homeostasis. Women smokers have higher
      testosterone and lower estradiol levels throughout life compared to nonsmokers.
      We monitored the effect of smoking discontinuation on steroid spectrum with 25
      postmenopausal women smokers. They had been examined before discontinuation of
      smoking and after 6, 12, 24 and 48 weeks of abstinence. Blood was collected to
      determine steroid spectrum (measured by GC-MS), luteinizing hormone, follicle
      stimulating hormone and sex hormone binding globulin (measured by IRMA). Repeated
      measures ANOVA model was used for evaluation of the data. In postmenopausal
      women, an increase in testosterone, dihydrotestosterone, dehydroepiandrosterone
      and other androgens occurred. Neither nicotine replacement therapy nor weight
      changes nor age play a role in androgen level increase. The higher androgens
      levels correlated with failure in smoking cessation. Women smokers have higher
      androgen levels, which might play a role in smoking dependence development. Women
      successful in smoking cessation, compared to the non-successful ones, have lower
      androgen levels initially and also after smoking discontinuation. 

PMID- 24874936
TI  - Acalculous cholecystitis or biliary dyskinesia for Epstein-Barr virus gallbladder
      involvement?
AB  - We present two patients with Epstein-Barr virus (EBV) infection related to
      gallbladder involvement. Such an association is already known as EBV induced
      acalculous cholecystitis, diagnosed on the basis of ultrasonographic findings. In
      our patients, radioisotopic cholescintigraphy was also performed and it showed
      that gallbladder was visualized in both patients in contrast to that what can be
      observed in cases of cholecystitis. However, the value of ejection fraction was
      compatible with biliary dyskinesia. We, therefore, consider that impaired
      gallbladder contractility in EBV infection cases may actually represent biliary
      dyskinesia and not acalculous cholecystitis taking into account the radioisotopic
      findings and the self limited course of the disorder. 

PMID- 24874937
TI  - Treatment of a superficial mycosis by low-temperature plasma: a case report.
AB  - A case of dermatomycosis caused by zoophilic strain of Trichophyton interdigitale
      was treated by low-temperature plasma produced by direct current (DC) cometary
      discharge. The shortening of skin lesion persistence along with suppression of
      subjective discomfort and etiological agent was observed. 

PMID- 24874943
TI  - In-beam PET imaging for on-line adaptive proton therapy: an initial phantom
      study.
AB  - We developed and investigated a positron emission tomography (PET) system for use
      with on-line (both in-beam and intra-fraction) image-guided adaptive proton
      therapy applications. The PET has dual rotating depth-of-interaction measurable
      detector panels by using solid-state photomultiplier (SSPM) arrays and LYSO
      scintillators. It has a 44 mm diameter trans-axial and 30 mm axial field-of-view
      (FOV). A 38 mm diameter polymethyl methacrylate phantom was placed inside the
      FOV. Both PET and phantom axes were aligned with a collimated 179.2 MeV beam.
      Each beam delivered ~50 spills (0.5 s spill and 1.5 s inter-spill time, 3.8 Gy at
      Bragg peak). Data from each beam were acquired with detectors at a given angle.
      Nine datasets for nine beams with detectors at nine different angles over 180
      degrees  were acquired for full-tomographic imaging. Each dataset included data
      both during and 5 min after irradiations. The positron activity-range was
      measured from the PET image reconstructed from all nine datasets and compared to
      the results from simulated images. A (22)Na disc-source was also imaged after
      each beam to monitor the PET system's performance. PET performed well except for
      slight shifts of energy photo-peak positions (<1%) after each beam, due mainly to
      the neutron exposure of SSPM that increased the dark-count noise. This minor
      effect was corrected offline with a shifting 350-650 keV energy window for each
      dataset. The results show a fast converging of activity-ranges measured by the
      prototype PET with high sensitivity and uniform resolution. Sub-mm activity
      ranges were achieved with minimal 6 s acquisition time and three spill
      irradiations. These results indicate the feasibility of PET for intra-fraction
      beam-range verification. Further studies are needed to develop and apply a novel
      clinical PET system for on-line image-guided adaptive proton therapy. 

PMID- 24874944
TI  - Which chemicals drive biological effects in wastewater and recycled water?
AB  - Removal of organic micropollutants from wastewater during secondary treatment
      followed by reverse osmosis and UV disinfection was evaluated by a combination of
      four in-vitro cell-based bioassays and chemical analysis of 299 organic
      compounds. Concentrations detected in recycled water were below the Australian
      Guidelines for Water Recycling. Thus the detected chemicals were considered not
      to pose any health risk. The detected pesticides in the wastewater treatment
      plant effluent and partially advanced treated water explained all observed
      effects on photosynthesis inhibition. In contrast, mixture toxicity experiments
      with designed mixtures containing all detected chemicals at their measured
      concentrations demonstrated that the known chemicals explained less than 3% of
      the observed cytotoxicity and less than 1% of the oxidative stress response.
      Pesticides followed by pharmaceuticals and personal care products dominated the
      observed mixture effects. The detected chemicals were not related to the observed
      genotoxicity. The large proportion of unknown toxicity calls for effect
      monitoring complementary to chemical monitoring. 

PMID- 24874945
TI  - Genomic instability: Transcript elongation: pause at your peril.

PMID- 24874947
TI  - Cytogeography of essential oil chemotypes of Eremophila longifolia F. Muell
      (Scrophulariaceae).
AB  - Previous studies have demonstrated that the widely distributed desert plant
      Eremophila longifolia has at least six geographically defined essential oil
      chemotypes. The focus of the present study is to extend and enhance information
      concerning known chemotypes and to investigate the involvement of cell nuclei
      ploidy in this variation. Forty field collected specimens of E. longifolia were
      taken from most of the mainland states of Australia then subjected to
      hydrodistillation to produce essential oils, which were then chemically
      characterised. Ploidy was determined using relative fluorescence of cell nuclei
      stained with propidium iodide, measured in a flow cytometer. Using principal
      component analysis (PCA), at least three essential oil chemotypes, in addition to
      the six already described, were identified in the present study. Previously
      described high yielding essential oil chemotypes were also characterised in terms
      of diploidy. For the first time diploid populations were identified in New South
      Wales, correlating with high yielding isomenthone/menthone and karahanaenone
      chemotypes. Furthermore, the separate diploid population previously described
      from Western Australia was demonstrated to be the safrole/methyl eugenol type,
      which is restricted to a small geographic range in far north-west Western
      Australia (Murchison District). All other chemotypes were shown to be tetraploid,
      including apparently randomly emerging individuals, representative of chemotypes
      producing low yields of isomenthone/menthone and karahanaenone similar in
      composition to the high yielding diploid types. 

PMID- 24874948
TI  - Is visual-based, online control of manual-aiming movements disturbed when
      adapting to new movement dynamics?
AB  - Previous research has shown that for goal-directed movements, online visual
      feedback is not necessary for the adaptation of movement planning to novel
      movement dynamics. In the present study, we wanted to put this proposition to a
      stringent test and determine whether the usually dominant role of online visual
      feedback in movement control is diminished when goal-directed movements are
      performed in a condition that modifies limb dynamics. Participants performed a
      video-aiming task while the center of mass of their forearm was experimentally
      displaced by a 1.5-kg mass attached laterally to its longitudinal axis. A cursor
      representing the position of the participant's hand was either visible or not
      visible during the acquisition phase. Then, in a transfer test, the participants
      performed the task without online visual feedback and either with or without the
      lateral mass. During the acquisition phase, the participants adapted to the new
      movement dynamics imposed by the added mass regardless of whether online visual
      feedback was available. An important new finding of the present study was the
      observation that the role usually played by online visual feedback in refining
      movement planning and ensuring control of the initial portion of goal-directed
      movements was suppressed during adaptation to novel movement dynamics. This
      resulted in an increase in the role played by visual feedback late in the
      movement to ensure endpoint accuracy. 

PMID- 24874946
TI  - Activating transcription factor 6 is necessary and sufficient for alcoholic fatty
      liver disease in zebrafish.
AB  - Fatty liver disease (FLD) is characterized by lipid accumulation in hepatocytes
      and is accompanied by secretory pathway dysfunction, resulting in induction of
      the unfolded protein response (UPR). Activating transcription factor 6 (ATF6),
      one of three main UPR sensors, functions to both promote FLD during acute stress
      and reduce FLD during chronic stress. There is little mechanistic understanding
      of how ATF6, or any other UPR factor, regulates hepatic lipid metabolism to cause
      disease. We addressed this using zebrafish genetics and biochemical analyses and
      demonstrate that Atf6 is necessary and sufficient for FLD. atf6 transcription is
      significantly upregulated in the liver of zebrafish with alcoholic FLD and
      morpholino-mediated atf6 depletion significantly reduced steatosis incidence
      caused by alcohol. Moreover, overexpression of active, nuclear Atf6 (nAtf6) in
      hepatocytes caused FLD in the absence of stress. mRNA-Seq and qPCR analyses of
      livers from five day old nAtf6 transgenic larvae revealed upregulation of genes
      promoting glyceroneogenesis and fatty acid elongation, including fatty acid
      synthase (fasn), and nAtf6 overexpression in both zebrafish larvae and human
      hepatoma cells increased the incorporation of 14C-acetate into lipids. Srebp
      transcription factors are key regulators of lipogenic enzymes, but reducing Srebp
      activation by scap morpholino injection neither prevented FLD in nAtf6
      transgenics nor synergized with atf6 knockdown to reduce alcohol-induced FLD. In
      contrast, fasn morpholino injection reduced FLD in nAtf6 transgenic larvae and
      synergistically interacted with atf6 to reduce alcoholic FLD. Thus, our data
      demonstrate that Atf6 is required for alcoholic FLD and epistatically interacts
      with fasn to cause this disease, suggesting triglyceride biogenesis as the
      mechanism of UPR induced FLD.

PMID- 24874949
TI  - Effects of postmortem interval on mouse ovary oocyte survival and maturation.
AB  - To study the time- and temperature-dependent survival of ovarian oocytes
      collected from postmortem carcass, ICR mice were killed and placed for different
      periods (0, 1, 2, 4, 6, 8 and 10 h) at different temperatures (25 degrees C, 4
      degrees C and 37 degrees C). After preservation, oocyte morphology, germinal
      vesicle (GV) oocyte number, oocyte meiotic maturation percentage, mitochondrial
      distribution and intracellular glutathione (GSH) level were evaluated. The
      results showed no surviving oocytes could be collected by 2h, 6h, and 12 h after
      carcass preservation at 37 degrees C, 25 degrees C and 4 degrees C, respectively.
      The number of collected GV oocytes in the ovary deceased as the preservation time
      lasted at the same temperature. Meanwhile at the same point in time, the ratio of
      germinal vesicle breakdown (GVBD) and the first polar body emission (PBE)
      gradually reduced as preservation temperature increased. In addition, the
      percentage of abnormal mitochondrial distribution in the preserved oocytes was
      obviously higher than that in the control oocytes, while GSH level was not
      altered in collected oocytes. Unexpectedly, neither chromosome arrangement nor
      spindle organization was affected as long as the oocytes from preserved carcasses
      could complete maturation. These data are helpful for proper use of ovary oocytes
      from postmortem carcass of valuable individuals. 

PMID- 24874950
TI  - The concentrations of ambient Burkholderia pseudomallei during typhoon season in
      endemic area of melioidosis in Taiwan.
AB  - BACKGROUND: Melioidosis is a severe bacterial infection caused by Burkholderia
      pseudomallei with a high case-fatality rate. Epidemiological and animal studies
      show the possibility of inhalation transmission. However, no B. pseudomallei
      concentrations in ambient air have been researched. Here, we developed a method
      to quantify ambient B. pseudomallei and then measured concentrations of ambient
      B. pseudomallei during the typhoon season and the non-typhoon season to determine
      the factors influencing ambient B. pseudomallei levels. METHODS: We quantified
      ambient B. pseudomallei by using a filter/real-time qPCR method in the Zoynan
      Region in Kaohsiung, southern Taiwan. Twenty-four hour samples were collected at
      a sampling rate of 20 L/min every day from June 11 to December 21, 2012 including
      during the typhoon season (June to September) and reference season (October to
      December). RESULTS: We successfully developed a filtration/real-time qPCR method
      to quantify ambient B. pseudomallei. To our knowledge, this is the first report
      describing concentrations of ambient B. pseudomallei. Ambient B. pseudomallei
      were only detected during the typhoon season when compared to the reference
      season. For the typhoons affecting the Zoynan Region, the positive rates of
      ambient B. pseudomallei were very high at 80% to 100%. During June to December,
      rainfall was positively correlated with ambient B. pseudomallei with a
      statistical significance. Sediment at a nearby pond significantly influenced the
      concentration of ambient B. pseudomallei. During the typhoon month, the typhoon
      was positively correlated with ambient B. pseudomallei whereas wind speed was
      reversely correlated with ambient B. pseudomallei. CONCLUSIONS: Our data suggest
      the possibility of transmission of B. pseudomallei via inhalation during the
      typhoon season.

PMID- 24874952
TI  - Perceived changes by peer group of social impact associated with combined
      orthodontic-surgical correction of class III malocclusion.
AB  - OBJECTIVES: Whereas the psychosocial benefits of orthognathic treatment for the
      individual patient are established, there is little data relating to social
      perceptions in relation to changes in facial appearance as a result of combined
      orthodontic and orthognathic treatment. This study aimed to investigate the
      social impact of combined orthodontic-orthognathic surgical correction for class
      III malocclusion in Caucasian subjects. METHODS: This cross-sectional study
      compared perceptions of facial appearance prior to and after orthognathic
      correction of class III malocclusion. Eighty undergraduate students were shown
      photographs of four Caucasian subjects (2 male and 2 female) pre- and post
      orthognathic class III correction. Observers were asked to rate these subjects in
      relation to four different outcomes: (i) social competence (SC); (ii)
      intellectual ability (IA); (iii) psychological adjustment (PA); (iv)
      attractiveness. A mixed-model analysis of variance (ANOVA) was calculated to
      determine the effect of each variable. RESULTS: Statistically significant
      differences were found in ratings of the same face before and after treatment.
      After treatment, faces were rated as more psychologically adjusted, more
      sociable, more likely to be successful and more attractive; with the mean
      psychological adjustment rating being associated with the most change (before
      treatment=8.06 [SD 2.30]; after treatment=6.64 [SD 2.03], t=2.04, p<0.001).
      CONCLUSIONS: After combined orthodontic-orthognathic correction of class III
      malocclusion in Caucasians, individuals are rated by young adults as being better
      adjusted both psychologically and socially, more likely to be successful and more
      attractive.

PMID- 24874951
TI  - Physico-mechanical characteristics of commercially available bulk-fill
      composites.
AB  - OBJECTIVES: Bulk-fill composites have emerged, arguably, as a new "class" of
      resin-based composites, which are claimed to enable restoration in thick layers,
      up to 4mm. The objective of this work was to compare, under optimal curing
      conditions, the physico-mechanical properties of most currently available bulk
      fill composites to those of two conventional composite materials chosen as
      references, one highly filled and one flowable "nano-hybrid" composite. METHODS:
      Tetric EvoCeram Bulk Fill (Ivoclar-Vivadent), Venus Bulk Fill (Heraeus-Kulzer),
      SDR (Dentsply), X-tra Fil (VOCO), X-tra Base (VOCO), Sonic Fill (Kerr), Filtek
      Bulk Fill (3M-Espe), Xenius (GC) were compared to the two reference materials.
      The materials were light-cured for 40s in a 2mm*2mm*25mm Teflon mould. Degree of
      conversion was measured by Raman spectroscopy, Elastic modulus and flexural
      strength were evaluated by three point bending, surface hardness using Vickers
      microindentation before and after 24h ethanol storage, and filler weight content
      by thermogravimetric analysis. The ratio of surface hardness before and after
      ethanol storage was considered as an evaluation of polymer softening. Data were
      analyzed by one-way ANOVA and post hoc Tukey's test (p=0.05). RESULTS: The
      mechanical properties of the bulk-fill composites were mostly lower compared with
      the conventional high viscosity material, and, at best, comparable to the
      conventional flowable composite. Linear correlations of the mechanical properties
      investigated were poor with degree of conversion (0.09<R<0.41) and good with
      filler content (R>0.8). Softening in ethanol revealed differences in polymer
      network density between material types. CONCLUSION: The reduction of time and
      improvement of convenience associated with bulk-fill materials is a clear
      advantage of this particular material class. However, a compromise with
      mechanical properties compared with more conventional commercially-available nano
      hybrid materials was demonstrated by the present work. SIGNIFICANCE: Given the
      lower mechanical properties of most bulk-fill materials compared to a highly
      filled nano-hybrid composite, their use for restorations under high occlusal load
      is subject to caution. Further, the swelling behaviour of some of the bulk-fill
      materials may be a reason for concern, which highlights the critical requirement
      for a veneering material, not only to improve aesthetic quality of the
      translucent material, but to reduce the impact of degradation.

PMID- 24874953
TI  - Heritable/conditional genome editing in C. elegans using a CRISPR-Cas9 feeding
      system.

PMID- 24874955
TI  - The soft underbelly of tumor cells.
AB  - In a recent Cell paper, Kitambi and colleagues identify a small molecule
      (Vacquinol-1) that has beneficial effects on a glioblastoma multiforme mouse
      model by oral administration. In glioblastoma cells, Vacquinol-1 targets
      macropinocytosis, a cellular process that will not lead to cell death in normal
      cells. 

PMID- 24874956
TI  - Proceedings of the Annual Symposium & Plenary Session on Regenerative Medicine
      (PASRM).

PMID- 24874957
TI  - Enantiopure pillar[5]arene active domains within a homochiral metal-organic
      framework.
AB  - Enantiopure struts containing pillar[5]arenes incorporating planar chirality have
      been linked together with Zn4O clusters in order to create metal-organic
      frameworks that include homochiral active domains and so have the potential to
      act as a solid support in chiral chromatography. 

PMID- 24874954
TI  - An epigenomic approach to therapy for tamoxifen-resistant breast cancer.
AB  - Tamoxifen has been a frontline treatment for estrogen receptor alpha (ERalpha)
      positive breast tumors in premenopausal women. However, resistance to tamoxifen
      occurs in many patients. ER still plays a critical role in the growth of breast
      cancer cells with acquired tamoxifen resistance, suggesting that ERalpha remains
      a valid target for treatment of tamoxifen-resistant (Tam-R) breast cancer. In an
      effort to identify novel regulators of ERalpha signaling, through a small-scale
      siRNA screen against histone methyl modifiers, we found WHSC1, a histone H3K36
      methyltransferase, as a positive regulator of ERalpha signaling in breast cancer
      cells. We demonstrated that WHSC1 is recruited to the ERalpha gene by the BET
      protein BRD3/4, and facilitates ERalpha gene expression. The small-molecule BET
      protein inhibitor JQ1 potently suppressed the classic ERalpha signaling pathway
      and the growth of Tam-R breast cancer cells in culture. Using a Tam-R breast
      cancer xenograft mouse model, we demonstrated in vivo anti-breast cancer activity
      by JQ1 and a strong long-lasting effect of combination therapy with JQ1 and the
      ER degrader fulvestrant. Taken together, we provide evidence that the epigenomic
      proteins BRD3/4 and WHSC1 are essential regulators of estrogen receptor signaling
      and are novel therapeutic targets for treatment of Tam-R breast cancer. 

PMID- 24874958
TI  - Histochemical study of biogenic monoamines in early ("Prenervous") and late
      embryos of sea urchins.
AB  - Treatment of the embryos of sea urchins with glyoxylic acid results in the
      appearance of luminescence which is indicative of the presence of biogenic
      monoamines. At the early stages of development (cleavage divisions, blastula,
      gastrula) the histochemical method reveals a tryptamine-like substance which is
      first found in all embryonic cells and later is concentrated mainly in the cells
      of the primary gut and ciliary bands. At the stages of prism and pluteus there
      appear neuron-like cells containing dopamine. The inhibitors of monoamine oxidase
      and neurotoxins reliably increase the histochemical reaction to monoamines only
      in late embryos which suggests a change in the properties of monoaminergic
      systems in the course of embryogenesis. 

PMID- 24874959
TI  - Prenatal treatment with 6-hydroxydopa and DSP 4: Biochemical, endocrinological
      and behavioural effects.
AB  - Biochemical, hormonal, and behavioural aspects of the effects of prenatal
      treatment (foetal days 18 and 19) with 6-hydroxydopa (2 * 40 mg/kg) and DSP 4 (2
      * 20 mg/kg) have been studied in the rat. The results of the catecholamine assays
      suggest that the 6-hydroxydopa treatment produced a transient decrease of
      noradrenaline concentration in the cerebral cortex, and a long-lasting decrease
      in the cerebellum, whereas DSP 4 produced a long-lasting decrease in the cerebral
      cortex and a tendency towards increase in the cerebellum. Assays of
      adrenocorticotropic hormone and corticosterone indicated a general tendency
      towards increase in base line as well as in moderate stress situations. The
      results of behavioural tests indicated hyperactivity and/or hyperreactivity, but
      not restlessness, and partly supranormal sensorimotor performances. 

PMID- 24874960
TI  - Development of muscimol binding sites in chick embryo neural retina in vivo and
      in vitro: Regulatory effects of cyclic AMP.
AB  - We report here the development in the chick embryo retina of binding sites for
      [(3)H]muscimol, a potent agonist of GABA receptors. In vivo studies were carried
      out with isolated neural retinas from different stages of development. High
      affinity binding sites were absent before embryonic day (E) 8, but increased
      conspicuously between E10 and E16. Scatchard analysis indicated that this rise
      was due to an increase in the number of binding sites. Kinetic parameters of the
      embryonic binding sites were consistent with those typically found for mature
      muscimol receptors. Measurements of the low-affinity binding site showed a
      relatively similar developmental pattern although a pronounced decrease in
      binding to the low-affinity site was observed between E12 and E14. In vitro
      studies were carried out using glial-free, purified monolayers of retinal
      neurons, starting at E8. Cultured retinal neurons showed a developmental pattern
      for high-affinity muscimol binding sites resembling that observed in ovo. These
      binding sites were susceptible to regulation by cyclic AMP analogues. Increases
      of 100 to 200% in muscimol binding could be induced by a 24 hr treatment with
      dibutyryl cyclic AMP, 8-bromo cyclic AMP, or the phosphodiesterase inhibitor
      IBMX. Scatchard analysis showed that this increase was due to a change in
      receptor affinity. No effects were found with either butyric acid or with
      adenosine 5'-monophosphate. These results raise the possibility that cyclic AMP
      may be involved in the regulation of components of the GABA system. 

PMID- 24874961
TI  - Effect of glucocorticoids on development of the membrane resting potential of
      chick embryo brain cells in culture.
AB  - Progressive increase in membrane resting potential (MRP) values in cultured chick
      embryo brain neurons were recorded from days 2 to 10 of development. Application
      of corticosterone or prednisone in 24 hr old cultured cells caused a significant
      increment in MRP recorded at day 2 of culture with respect to control. When
      ouabain was added to the corticosterone treated cells its effect on the MRP was
      impaired. An increment in protein synthesis and a reduction in sodium
      concentration were also observed in corticosterone pretreated cells. These
      results show that corticoids accelerate the differentiation process in cultured
      cells particularly the MRP, stimulating perhaps the Na(+)-K(+) ATPase pump. 

PMID- 24874962
TI  - The phagocytes of neonate rat primary mixed glial cultures.
AB  - The phagocytes present in mechanically dissociated neonate rat cerebral
      hemispheres have been cultured and characterized both qualitatively and
      quantitatively. They comprise about 10% of the starting cell suspension and
      persist but do not proliferate in culture. They do not possess neuronal or
      neuroglial antigens but do express the leukocyte common antigen and readily
      ingest both latex beads and opsonized erythrocytes. the latter by an Fc receptor
      mediated process. Evidence is presented that these cells are a bona fida
      component of the neonate central nervous system. 

PMID- 24874963
TI  - Ontogeny of opiate receptors in the rat medial preoptic area: Critical periods in
      regional development.
AB  - Opiate receptor labeling was examined throughout the early postnatal period using
      autoradiography to localize and quantify [(3)H]naloxone binding to MU-type opiate
      receptors in the medial preoptic area (MPOA). This region begins to exhibit
      sexual dimorphism of volume and dendritic growth shortly after birth. A distinct
      concentration of opiate receptor labeling appears on postnatal day 3 in females:
      this labeling is directly associated with the sexually dimorphic nucleus of the
      preoptic area (SDN-POA). SDN-POA labeling becomes denser through postnatal day 10
      in females and the densely labeled area increases in size to encompass and
      surround the SDN-POA. These changes in opiate receptor labeling occur only in
      females, since males show relatively uniform labeling across the region
      throughout the early postnatal period. The critical time of formation of dense
      MPOA opiate receptor labeling may be related to endogenous MPOA opioid function
      and to the critical period of dendritic growth of SDN-POA neurons. The timing of
      these critical periods and their focus in the SDN-POA are coincident. The
      possible role of MPOA opiate receptors in modulating growth of MPOA neurons is
      discussed. 

PMID- 24874964
TI  - Histogenesis of the vestibular sensory epithelium in organotypic culture of mouse
      embryo otocysts: A tritiated thymidine autoradiographic study.
AB  - The cytogenesis in the vestibular sensory epithelium of mouse embryo otocysts
      grown in organ culture was examined using tritiated thymidine autoradiography.
      Pulse-labeling with [(3)H]-thymidine was applied either in vivo, at various
      intervals before explantation, or in vitro at specific stages of development.
      Observations of the development in vitro showed that the cytogenesis and
      cytodifferentiation of vestibular sensory cells were disturbed by explantation.
      By varying the intervals between the [(3)H]thymidine exposure and the date of
      explantation, we were able to demonstrate that explantation itself caused a
      significant decrease in the mitotic and the postmitotic phases of the hair cell
      precursors. Labeling of the expiants excised on day 13 of gestation revealed that
      precursors of the hair cells were progressively losing their mitotic capacity in
      vitro. In contrast with this finding, precursors of the supporting cells were
      less affected by explantation and culture conditions and they retained the
      capacity for survival, proliferation and differentiation. 

PMID- 24874965
TI  - The microtubular apparatus of cerebellar purkinje cell dendrites during postnatal
      development of the rat: The density and cold-stability of microtubules increase
      with age and are sensitive to thyroid hormone deficiency.
AB  - A quantitative ultrastructural study of microtubules in Purkinje cell dendrites
      of normal and hypothyroid developing rats was performed after fixation either at
      room or at low temperature (4 degrees C). In normal animals, the density of
      microtubules and their fold-stability increased with age, more especially during
      the period of intense dendritic growth. Thyroid deficiency delayed the appearance
      of microtubules and still more the acquisition of their fold-stability. These
      effects might explain the defects in Purkinje cell dendritic growth and branching
      observed in hypothyroid animals. 

PMID- 24874966
TI  - Effect of maternal nicotine on the development of sites for [(3)H]nicotine
      binding in the fetal brain.
AB  - The sites for [(3)H]nicotine binding in fetal brains were examined after
      administration of nicotine into pregnant rats. Administration of unlabelled
      nicotine into the pregnant rats increased Bmax values for the sites for
      [(3)H]nicotine binding without affecting Kd values in the fetal brains. Treatment
      with this regimen, however, did not show any significant change in the sites for
      [(3)H]quinuclidinyl benzylate (QNB) binding. In addition, treatment with this
      regimen increased Bmax values of the sites for [(3)H]nicotine binding in the
      brains of pregnant rats. alpha-Bungarotoxin had no effect on the sites for
      [(3)H]nicotine binding. It is inferred, therefore, that a similar response is
      elicited by nicotine binding sites to administered nicotine in both the fetal and
      maternal brains. Furthermore, a possible effect of nicotine in pregnant rats may
      be the facilitation of the development of nicotine acetylcholine receptors in the
      fetal brain. 

PMID- 24874967
TI  - Development of trochlear motor neurons, superior oblique muscle, and
      neuromuscular junctions following prevention of cell death by myasthenia gravis
      immunoglobulin.
AB  - Paralysis of embryo during the period of naturally occurring motor neuron death
      produces an increase in the number of surviving neurons while the progressive
      differentiation and maturation of target muscle is severely retarded. Application
      of immunoglobulin G from patients with acquired myasthenia gravis to duck embryos
      during the period of trochlear motor neuron death also prevents this neuron loss
      but without paralyzing the embryo. The present study was conducted to investigate
      whether or not the differentiation and maturation of motor neurons, target
      muscle, and neuromuscular junctions were retarded following prevention of cell
      loss with myasthenic immunoglobulin. Immunoglobulin concentrates from myasthenics
      and normal human volunteers were applied daily to the chorioallantoic membrane of
      duck embryos from day 10 onward. The development of the trochlear neurons and the
      superior oblique muscle was examined with light and electron microscopy on
      embryonic days 12, 16 and 20. The motor neurons at the light and electron
      microscopic level were cytologically indistinguishable between the myasthenic and
      normal immunoglobulin-treated embryos. Myoblasts fused to form myotubes. which
      further differentiated into mature myofibers at the same time in both groups.
      Numerous neuromuscular junctions of normal ultrastructure and nerve fibers with
      myelin wrappings were observed in both cases. It is concluded that the increased
      neuron survival following myasthenic immunoglobulin treatment does not accompany
      retardation in differentiation and maturation of the target muscle which is
      contrary to the results obtained from studies utilizing neuromuscular blocking
      agents producing increased cell survival. 

PMID- 24874968
TI  - Postnatal development of conduction velocity and fibre size in the rat tibial
      nerve.
AB  - The maximum conduction velocity (CV) and fibre diameters (D) were determined in
      the tibial nerve of developing rats. In 1-day-old rats CV of the fastest motor
      and sensory fibres (assessed separately) was 1.4 m/sec on the average and
      increased to 35 m/sec by postnatal day 30. The maximum conduction rate in adult
      rats ranged from 60 to 84 m/sec. Diameters of at least 100 nerve fibres in each
      age group were measured in electronmicrographs. The calibre of myelinating fibres
      in 1-day-old rats was 0.5-1.5 MUm. By day 90 after birth the range of myelinated
      fibre size extended to 1.5-12.5 MUm. The factor relating conduction rate and
      total fibre diameter of the largest fibres (i.e. the value of CV D ) was found to
      vary with age, increasing from 1.1 to 6.2 between postnatal days 1 and 90. These
      results indicate that functional and morphological properties of peripheral nerve
      fibres in the rat undergo considerable changes during postnatal ontogeny until
      they reach adult values. 

PMID- 24874969
TI  - Editorial note.

PMID- 24874970
TI  - Persistent super-diffusive motion of Escherichia coli chromosomal loci.
AB  - The physical nature of the bacterial chromosome has important implications for
      its function. Using high-resolution dynamic tracking, we observe the existence of
      rare but ubiquitous 'rapid movements' of chromosomal loci exhibiting near
      ballistic dynamics. This suggests that these movements are either driven by an
      active machinery or part of stress-relaxation mechanisms. Comparison with a null
      physical model for subdiffusive chromosomal dynamics shows that rapid movements
      are excursions from a basal subdiffusive dynamics, likely due to driven and/or
      stress-relaxation motion. Additionally, rapid movements are in some cases coupled
      with known transitions of chromosomal segregation. They do not co-occur strictly
      with replication, their frequency varies with growth condition and chromosomal
      coordinate, and they show a preference for longitudinal motion. These findings
      support an emerging picture of the bacterial chromosome as off-equilibrium active
      matter and help developing a correct physical model of its in vivo dynamic
      structure. 

PMID- 24874971
TI  - Swellable, water- and acid-tolerant polymer sponges for chemoselective carbon
      dioxide capture.
AB  - To impact carbon emissions, new materials for carbon capture must be inexpensive,
      robust, and able to adsorb CO2 specifically from a mixture of other gases. In
      particular, materials must be tolerant to the water vapor and to the acidic
      impurities that are present in gas streams produced by using fossil fuels to
      generate electricity. We show that a porous organic polymer has excellent CO2
      capacity and high CO2 selectivity under conditions relevant to precombustion CO2
      capture. Unlike polar adsorbents, such as zeolite 13x and the metal-organic
      framework, HKUST-1, the CO2 adsorption capacity for the hydrophobic polymer is
      hardly affected by the adsorption of water vapor. The polymer is even stable to
      boiling in concentrated acid for extended periods, a property that is matched by
      few microporous adsorbents. The polymer adsorbs CO2 in a different way from rigid
      materials by physical swelling, much as a sponge adsorbs water. This gives rise
      to a higher CO2 capacities and much better CO2 selectivity than for other water
      tolerant, nonswellable frameworks, such as activated carbon and ZIF-8. The
      polymer has superior function as a selective gas adsorbent, even though its
      constituent monomers are very simple organic feedstocks, as would be required for
      materials preparation on the large industrial scales required for carbon capture.

PMID- 24874972
TI  - Proteomic analysis of the soluble proteomes of miltefosine-sensitive and 
      resistant Leishmania infantum chagasi isolates obtained from Brazilian patients
      with different treatment outcomes.
AB  - The mechanism of miltefosine-resistance in Leishmania spp. has been partially
      determined in experimental resistant lines; however, studies using clinical
      isolates with different miltefosine susceptibilities are still needed. In our
      study, we used a proteomic 2D-DIGE/MS approach to study different protein
      abundances in miltefosine-sensitive and -resistant Leishmania infantum chagasi
      isolates from visceral leishmaniasis patients with different miltefosine
      treatment outcomes. The high-resolution proteome obtained from these isolates
      showed 823 matched spots and 46 spots exhibited different abundances between the
      isolates. Out of these differentially expressed spots, 26 (56.5%) showed greater
      and 20 (43.5%) showed lower expression of the resistant isolate compared to the
      sensitive isolate. MALDI/TOF-TOF mass spectrometry allowed the identification of
      32 spots with unique protein identification correspondent to 22 non-redundant
      proteins. Most of the proteins up-regulated in the proteome miltefosine-resistant
      isolates were associated with redox homeostasis, stress response, protection to
      apoptosis, and drug translocation. These differentially expressed proteins are
      likely involved in miltefosine natural resistance and suggest that the
      miltefosine-resistance mechanism in Leishmania is multifactorial. BIOLOGICAL
      SIGNIFICANCE: Visceral leishmaniasis (VL) is a serious disease with a challenging
      treatment plan requiring the prolonged and painful applications of poorly
      tolerated toxic drugs. Therefore, the identification of miltefosine, an effective
      and safe oral drug, was considered a significant advancement in leishmaniasis
      therapy. However, different sensitivities to miltefosine in Leishmania have been
      observed in clinically relevant species, and the biological mechanism by which
      clinical isolates of Leishmania acquire drug resistance is poorly understood. Our
      work aims to elucidate the mechanism of natural resistance to miltefosine in
      Leishmania by studying the isolates from VL patients who displayed different
      miltefosine treatment outcomes.

PMID- 24874973
TI  - Application of a parametric display of two-dimensional speckle-tracking
      longitudinal strain to improve the etiologic diagnosis of mild to moderate left
      ventricular hypertrophy.
AB  - BACKGROUND: The distinction of hypertrophic cardiomyopathy (HCM) or cardiac
      amyloidosis (CA) from hypertensive heart disease may be difficult. The aim of
      this study was to determine the impact of parametric (polar) maps of regional
      longitudinal strain on identification of the etiology of mild to moderate left
      ventricular hypertrophy (LVH). METHODS: Twenty-four consecutive echocardiographic
      studies with mild to moderate LVH (eight with CA, eight with HCM, and eight with
      hypertensive heart disease) were selected on the basis of the availability of
      adequate images to assess longitudinal strain and absence of electrocardiographic
      criteria for low voltage or LVH or a pseudoinfarct pattern. Twenty level 3
      trained readers provided the most likely of three diagnoses (CA, HCM, or
      hypertensive heart disease) and scored their confidence in making the diagnosis
      from two-dimensional images and diastolic parameters. A teaching exercise was
      provided on the interpretation of longitudinal strain in these cohorts, and
      interpretation was repeated with the addition of the strain polar map. RESULTS:
      Baseline concordance among the readers was poor (kappa = 0.28) and improved with
      the addition of strain data (kappa = 0.57). Accuracy was improved with the
      addition of polar maps for the entire study cohort (P < .001), with 22% of cases
      reclassified correctly. The largest improvements in sensitivity (from 40% to 86%,
      P < .001), specificity (from 84% to 95%, P < .001), and accuracy (from 70% to
      92%, P < .001) were seen for CA. The strain polar map significantly improved
      reader confidence in making the correct diagnosis overall (P < .001).
      CONCLUSIONS: Regional variations in strain are easily recognizable, accurate, and
      reproducible means of differentiating causes of LVH. The detection of LVH
      etiology may be a useful clinical application for strain.

PMID- 24874974
TI  - The role of multimodality imaging in percutaneous left atrial appendage suture
      ligation with the LARIAT device.
AB  - Atrial fibrillation (AF), the most common cardiac arrhythmia, is a significant
      cause of embolic stroke. Although systemic anticoagulation is the primary
      strategy for preventing the thromboembolic complications of AF, anticoagulants
      carry major bleeding risks, and many patients have contraindications to their
      use. Because thromboembolism typically arises from a clot in the left atrial
      appendage (LAA), local therapeutic alternatives to systemic anticoagulation
      involving surgical or percutaneous exclusion of the LAA have been developed.
      Surgical exclusion of the LAA is typically performed only as an adjunct to other
      cardiac surgeries, thus limiting the number of eligible patients. Furthermore,
      surgical exclusion of the LAA is frequently incomplete, and thromboembolism may
      still occur. Percutaneous LAA exclusion includes two approaches: transseptal
      delivery of an occlusion device to the LAA and epicardial suture ligation of the
      LAA, the LARIAT procedure. In the LARIAT procedure, a pretied snare is placed
      around the epicardial surface of the LAA orifice via pericardial access. Proper
      snare placement is achieved with epicardial and endocardial magnet-tipped
      guidewires. The endocardial wire is advanced transvenously to the LAA apex after
      transseptal puncture. The epicardial wire, introduced into the pericardial space,
      achieves end-to-end union with the endocardial wire at the LAA apex. The snare is
      then placed over the LAA, tightened, and sutured. On the basis of early clinical
      experience, the LARIAT procedure has a high success rate of LAA exclusion with
      low risk for complications. The authors describe the indispensable role of real
      time transesophageal echocardiography in the guidance of LAA epicardial suture
      ligation with the LARIAT device. 

PMID- 24874975
TI  - Outcomes of asymptomatic adults with combined aortic stenosis and regurgitation.
AB  - BACKGROUND: The outcomes of patients with mixed aortic valve disease (MAVD;
      concurrent aortic stenosis [AS] and aortic regurgitation [AR]) and its optimum
      management are undefined. The aim of this study was to evaluate the natural
      history of MAVD. METHODS: Between 2000 and 2005, 524 asymptomatic adults (mean
      age, 66 +/- 14 years; 306 men) were identified who had mixed AS and AR, who did
      not undergo early intervention with surgery. The severity of AS and AR was
      defined using American Society of Echocardiography guideline criteria. Patients
      were followed over 5.5 +/- 3.1 years. RESULTS: Aortic valve replacement (AVR) was
      performed in 349 patients (67%), and 88 (17%) died. Angina, dyspnea, or syncope
      developed in 292 patients (84%) before AVR; baseline left ventricular mass and
      the severity of AS and AR were independent predictors of progression to AVR in
      the overall group. Survival was associated with younger age (hazard ratio, 1.08;
      P < .001) and valve replacement (hazard ratio, 0.61; P = .02). Most patients with
      MAVD in the moderate category progressed to severe AS or AR by the time of
      surgery (n = 51 [27%]); symptoms were the main indication in 22 patients. In this
      group, AVR was associated with age, left ventricular function, valve area, and
      the change in peak gradient over follow-up. In patients with moderate MAVD,
      coronary artery disease was present in 38 (20%) at baseline and developed in 21
      (21%) during follow-up but was not associated with surgery. The average time to
      an event (AVR or death) in patients with MAVD was 4 years. CONCLUSIONS: Careful
      surveillance of patients with MAVD is warranted, bearing in mind the composite
      severity of both AS and AR and their combined hemodynamic effects.

PMID- 24874976
TI  - Altered immunohistochemical expression of mast cell tryptase and chymase in the
      pathogenesis of oral submucous fibrosis and malignant transformation of the
      overlying epithelium.
AB  - Mast cells (MCs) expressing serine proteases; tryptase and chymase, are
      associated with fibrosis in various diseases. However, little is known about
      their involvement in oral submucous fibrosis (OSF). Our goal was to evaluate the
      role of MC tryptase and chymase in the pathogenesis of OSF and its malignant
      transformation. Immunohistochemical expression of MC tryptase and chymase was
      evaluated in 20 cases of OSF, 10 cases of oral squamous cell carcinoma (OSCC) and
      10 cases of healthy controls. Subepithelial zone of Stage 1 and 2 while deep zone
      of Stage 3 and 4 OSF demonstrated increased tryptase positive MCs. OSCC revealed
      a proportionate increase in tryptase and chymase positive MCs irrespective of
      areas of distribution. An altered balance in the subepithelial and deep
      distribution of tryptase and chymase positive MCs play an important role in the
      pathogenesis of OSF and its malignant transformation. 

PMID- 24874978
TI  - Correlation between cognition and symptomatic severity in patients with late-life
      somatoform disorders.
AB  - OBJECTIVES: Various aging associated factors, such as functional decline,
      psychosocial problems, and cognitive dysfunction, are risk factors for somatoform
      disorders (SDs) in the elderly. The aim of the present study was to evaluate how
      cognition is correlated with the severity of late-life SDs from a
      neuropsychological viewpoint. METHODS: Fifty-three patients over 60 years of age
      who had been diagnosed as having SDs were examined in this study. The severity of
      the somatic symptoms was assessed using the Hamilton Anxiety Rating Scales
      (HAMA). Cognitive functions were assessed using the Mini-Mental State Examination
      (MMSE), the Frontal Assessment Battery (FAB), and the Japanese version of the
      Neurobehavioral Cognitive Examination (J-COGNISTAT). RESULTS: The J-COGNISTAT
      subtest score for attention was below the cutoff point (8 points) but was not
      correlated with the severity of the somatic symptoms in the patients with late
      life SDs. The severity of anxiety as assessed using the HAMA was significantly
      correlated with the calculation scores (P < 0.005) among the J-COGNISTAT
      subtests, the FAB total (P < 0.05), and the FAB subtest scores (similarities and
      motor series) (P < 0.01). Other factors, including the benzodiazepine dosage,
      antidepressant dosage, the duration of illness, and the onset age, were not
      significantly correlated with the symptomatic severities. CONCLUSION: Patients
      with late-life SDs showed attention deficits, but no correlation was seen between
      the attention deficits and symptomatic severities. Attention deficits might be
      associated with the appearance of symptoms. Executive dysfunction and working
      memory might be associated with the severity of symptoms.

PMID- 24874977
TI  - Higher potency statins and the risk of new diabetes: multicentre, observational
      study of administrative databases.
AB  - OBJECTIVE: To evaluate the incremental increase in new onset diabetes from higher
      potency statins compared with lower potency statins when used for secondary
      prevention. DESIGN: Eight population based cohort studies and a meta-analysis.
      SETTING: Six Canadian provinces and two international databases from the UK and
      US. PARTICIPANTS: 136,966 patients aged >= 40 years newly treated with statins
      between 1 January 1997 and 31 March 2011. METHODS: Within each cohort of patients
      newly prescribed a statin after hospitalisation for a major cardiovascular event
      or procedure, we performed as-treated, nested case-control analyses to compare
      diabetes incidence in users of higher potency statins with incidence in users of
      lower potency statins. Rate ratios of new diabetes events were estimated using
      conditional logistic regression on different lengths of exposure to higher
      potency versus lower potency statins; adjustment for confounding was achieved
      using high dimensional propensity scores. Meta-analytic methods were used to
      estimate overall effects across sites. MAIN OUTCOME MEASURES: Hospitalisation for
      new onset diabetes, or a prescription for insulin or an oral antidiabetic drug.
      RESULTS: In the first two years of regular statin use, we observed a significant
      increase in the risk of new onset diabetes with higher potency statins compared
      with lower potency agents (rate ratio 1.15, 95% confidence interval 1.05 to
      1.26). The risk increase seemed to be highest in the first four months of use
      (rate ratio 1.26, 1.07 to 1.47). CONCLUSIONS: Higher potency statin use is
      associated with a moderate increase in the risk of new onset diabetes compared
      with lower potency statins in patients treated for secondary prevention of
      cardiovascular disease. Clinicians should consider this risk when prescribing
      higher potency statins in secondary prevention patients.

PMID- 24874986
TI  - Expansion of ocular phenotypic features associated with mutations in ADAMTS18.
AB  - IMPORTANCE: We describe novel ocular phenotypic features caused by mutations in
      ADAMTS18. The exact role of ADAMTS18 in ocular disease is unclear, and our work
      further contributes to the understanding of this gene and its protein. OBJECTIVE:
      To expand the phenotypic characterization in patients with homozygous mutations
      in ADAMTS18 and report novel mutational data. DESIGN, SETTING, AND PARTICIPANTS:
      A case series with genetic investigations was conducted at tertiary referral
      clinical and university settings. Three families participated. MAIN OUTCOME
      MEASURES: Phenotype and genotype description of 3 families. RESULTS: Four
      affected patients from 3 families with an unusual ocular phenotype had full
      ophthalmic and systemic examination. A single affected individual in the first
      family had bilateral microcornea, ectopic pupils, and cone-rod dystrophy. In a
      second family, 2 brothers showed bilateral microcornea, childhood cataract,
      ectopia lentis, rhegmatogenous retinal detachment, and cone-rod dystrophy. In the
      third family, a single affected individual had the same features as those in
      family 2, without ectopia lentis. Causative mutations were sought using
      homozygosity mapping, Sanger sequencing, and massively parallel sequencing of the
      whole exome. Novel homozygous mutations in ADAMTS18 were identified, consisting
      of c.1067T>A [p.L356*] in the first proband, c.2159G>C [p.C720S] in the 2
      affected brothers, and c.1952G>A [p.R651Q] in the third proband. All 3 mutations
      are predicted to be pathogenic. CONCLUSIONS AND RELEVANCE: Mutations in ADAMTS18
      are associated with ocular developmental abnormalities including microcornea,
      ectopia lentis, and early onset of cone-rod dystrophy. This report provides
      further evidence that ADAMTS18 plays a key role in ocular development. Physicians
      should consider screening ADAMTS18 in patients with microcornea and cone-rod
      dystrophy.

PMID- 24874987
TI  - Usability evaluation of pharmacogenomics clinical decision support aids and
      clinical knowledge resources in a computerized provider order entry system: a
      mixed methods approach.
AB  - BACKGROUND: Pharmacogenomics (PGx) is positioned to have a widespread impact on
      the practice of medicine, yet physician acceptance is low. The presentation of
      context-specific PGx information, in the form of clinical decision support (CDS)
      alerts embedded in a computerized provider order entry (CPOE) system, can aid
      uptake. Usability evaluations can inform optimal design, which, in turn, can spur
      adoption. OBJECTIVES: The study objectives were to: (1) evaluate an early
      prototype, commercial CPOE system with PGx-CDS alerts in a simulated environment,
      (2) identify potential improvements to the system user interface, and (3)
      understand the contexts under which PGx knowledge embedded in an electronic
      health record is useful to prescribers. METHODS: Using a mixed methods approach,
      we presented seven cardiologists and three oncologists with five hypothetical
      clinical case scenarios. Each scenario featured a drug for which a gene encoding
      drug metabolizing enzyme required consideration of dosage adjustment. We used
      Morae((r)) to capture comments and on-screen movements as participants prescribed
      each drug. In addition to PGx-CDS alerts, 'Infobutton((r))' and 'Evidence' icons
      provided participants with clinical knowledge resources to aid decision-making.
      RESULTS: Nine themes emerged. Five suggested minor improvements to the CPOE user
      interface; two suggested presenting PGx information through PGx-CDS alerts using
      an 'Infobutton' or 'Evidence' icon. The remaining themes were strong
      recommendations to provide succinct, relevant guidelines and dosing
      recommendations of phenotypic information from credible and trustworthy sources;
      any more information was overwhelming. Participants' median rating of PGx-CDS
      system usability was 2 on a Likert scale ranging from 1 (strongly agree) to 7
      (strongly disagree). CONCLUSIONS: Usability evaluation results suggest that
      participants considered PGx information important for improving prescribing
      decisions; and that they would incorporate PGx-CDS when information is presented
      in relevant and useful ways.

PMID- 24874990
TI  - The Safety of Women on College Campuses: Implications of Evolving Paradigms in
      Postsecondary Education.

PMID- 24874992
TI  - The safety of women on college campuses: implications of evolving paradigms in
      postsecondary education.

PMID- 24874991
TI  - Using virtual reality to explore self-regulation in high-risk settings.
AB  - Virtual reality (VR) models allow investigators to explore high-risk situations
      carefully in the laboratory using physiological assessment strategies and
      controlled conditions not available in field settings. This article introduces
      the use of a virtual experience to examine the influence of self-regulatory
      skills training on female participants' reactions to a high-risk encounter with
      an aggressive male. Sixty-three female participants were recruited for the study.
      Demographic data indicated that 54% of the participants were not currently in a
      relationship, 36.5% were in a committed relationship, and 9.5% were occasionally
      dating. After obtaining informed consent, participants were assigned randomly to
      either a diaphragmatic breathing training condition or an attention control
      condition. Results indicated that both groups rated the virtual environment as
      equally realistic; the aggressive advances of the male were also perceived as
      equally real across the two experimental groups. Physiological data indicated
      that there were no differences between the groups on respiration or
      cardiovascular measures during baseline or during the VR task. After the VR
      experience, however, the participants in the breathing training condition had
      lower respiration rates and higher heart rate variability measures than those in
      the control condition. The results suggest that VR platforms provide a realistic
      and challenging environment to examine how self-regulation procedures may
      influence behavioral outcomes. Real-time dynamic engagement in a virtual setting
      affords investigators with an opportunity to evaluate the utility of self
      regulatory skills training for improving safety in situations where there are
      uncertain and risky outcomes. 

PMID- 24874993
TI  - The Significant Frequency and Impact of Stealth (Nonviolent) Gender-Based Abuse
      Among College Women.
AB  - The prevalence, incidence, and impact of the gender-based abuse (GBA) of college
      women have been increasingly documented since the 1980s, with growing precision
      in the measurements and expanding identification of tactics. Although there is an
      obvious class bias in focusing on college women (compared to women of similar
      ages not attending college), it is important to address GBA among this population
      as they are at serious risk of sexual abuse (particularly incapacitated rape),
      intimate partner abuse (IPA), and stalking. This article addresses the stealth
      nature of the nonviolent GBAs of college women and how these abuses frequently
      operate under the radar of acknowledgment by society, the abusers, campus
      officials, the criminal legal system, and sometimes, the survivors.

PMID- 24874988
TI  - How duplicated transcription regulators can diversify to govern the expression of
      nonoverlapping sets of genes.
AB  - The duplication of transcription regulators can elicit major regulatory network
      rearrangements over evolutionary timescales. However, few examples of
      duplications resulting in gene network expansions are understood in molecular
      detail. Here we show that four Candida albicans transcription regulators that
      arose by successive duplications have differentiated from one another by
      acquiring different intrinsic DNA-binding specificities, different preferences
      for half-site spacing, and different associations with cofactors. The combination
      of these three mechanisms resulted in each of the four regulators controlling a
      distinct set of target genes, which likely contributed to the adaption of this
      fungus to its human host. Our results illustrate how successive duplications and
      diversification of an ancestral transcription regulator can underlie major
      changes in an organism's regulatory circuitry. 

PMID- 24874989
TI  - Role of LDB1 in the transition from chromatin looping to transcription
      activation.
AB  - Many questions remain about how close association of genes and distant enhancers
      occurs and how this is linked to transcription activation. In erythroid cells,
      lim domain binding 1 (LDB1) protein is recruited to the beta-globin locus via
      LMO2 and is required for looping of the beta-globin locus control region (LCR) to
      the active beta-globin promoter. We show that the LDB1 dimerization domain (DD)
      is necessary and, when fused to LMO2, sufficient to completely restore LCR
      promoter looping and transcription in LDB1-depleted cells. The looping function
      of the DD is unique and irreplaceable by heterologous DDs. Dissection of the DD
      revealed distinct functional properties of conserved subdomains. Notably, a
      conserved helical region (DD4/5) is dispensable for LDB1 dimerization and
      chromatin looping but essential for transcriptional activation. DD4/5 is required
      for the recruitment of the coregulators FOG1 and the nucleosome remodeling and
      deacetylating (NuRD) complex. Lack of DD4/5 alters histone acetylation and RNA
      polymerase II recruitment and results in failure of the locus to migrate to the
      nuclear interior, as normally occurs during erythroid maturation. These results
      uncouple enhancer-promoter looping from nuclear migration and transcription
      activation and reveal new roles for LDB1 in these processes. 

PMID- 24874994
TI  - Modelling the binding affinity of steroids to zebrafish sex hormone-binding
      globulin.
AB  - The circulating endogenous steroids are transported in the bloodstream. These are
      bound to a highly specific sex hormone-binding globulin (SHBG) and in lower
      affinity to proteins such as the corticosteroid-binding protein and albumin in
      vertebrates, including fish. It is generally believed that the glycoprotein SHBG
      protects these steroids from rapid metabolic degradation and thus intervenes in
      its availability at the target tissues. Endocrine disrupters binding to SHBG
      affect the normal activity of natural steroids. Since xenobiotics are primarily
      released in the aquatic environment, there is a need to evaluate the binding
      affinity of xenosteroid mimics on fish SHBG, especially in zebrafish (Danio
      rerio), a small freshwater fish originating in India and widely employed in
      ecotoxicology, toxicology, and genetics. In this context, a zebrafish SHBG
      (zfSHBG) homology model was developed using the human SHBG (hSHBG) receptor
      structure as template. It was shown that interactions with amino acids Ser-36,
      Asp-59 and Thr-54 were important for binding affinity. A ligand-based
      pharmacophore model was also developed for both zfSHBG and hSHBG inhibitors that
      differentiated binders from non-binders, but also demonstrated structural
      requirements for zfSHBG and hSHBG ligands. The study provides insights into the
      mechanism of action of endocrine disruptors in zebrafish as well as providing a
      useful tool for identifying anthropogenic compounds inhibiting zfSHBG. 

PMID- 24874995
TI  - Calcium-43 chemical shift and electric field gradient tensor interplay: a
      sensitive probe of structure, polymorphism, and hydration.
AB  - Calcium is the 5th most abundant element on earth, and is found in numerous
      biological tissues, proteins, materials, and increasingly in catalysts. However,
      due to a number of unfavourable nuclear properties, such as a low magnetogyric
      ratio, very low natural abundance, and its nuclear electric quadrupole moment,
      development of solid-state (43)Ca NMR has been constrained relative to similar
      nuclides. In this study, 12 commonly-available calcium compounds are analyzed
      via(43)Ca solid-state NMR and the information which may be obtained by the
      measurement of both the (43)Ca electric field gradient (EFG) and chemical shift
      tensors (the latter of which are extremely rare with only a handful of literature
      examples) is discussed. Combined with density functional theory (DFT)
      computations, this 'tensor interplay' is, for the first time for (43)Ca,
      illustrated to be diagnostic in distinguishing polymorphs (e.g., calcium
      formate), and the degree of hydration (e.g., CaCl2.2H2O and calcium tartrate
      tetrahydrate). For Ca(OH)2, we outline the first example of (1)H to (43)Ca cross
      polarization on a sample at natural abundance in (43)Ca. Using prior knowledge of
      the relationship between the isotropic calcium chemical shift and the calcium
      quadrupolar coupling constant (CQ) with coordination number, we postulate the
      coordination number in a sample of calcium levulinate dihydrate, which does not
      have a known crystal structure. Natural samples of CaCO3 (aragonite polymorph)
      are used to show that the synthetic structure is present in nature. Gauge
      including projector augmented-wave (GIPAW) DFT computations using accepted
      crystal structures for many of these systems generally result in calculated NMR
      tensor parameters which are in very good agreement with the experimental
      observations. This combination of (43)Ca NMR measurements with GIPAW DFT
      ultimately allows us to establish clear correlations between various solid-state
      (43)Ca NMR observables and selected structural parameters, such as unit cell
      dimensions and average Ca-O bond distances. 

PMID- 24874996
TI  - Impact of a diverting stoma in an enhanced recovery programme for rectal cancer.
AB  - PURPOSE: The association of a loop ileostomy decreases the severity of
      complications after rectal surgery but can increase the postoperative stay. The
      aim of this study is to investigate if a diverting ileostomy influences the
      postoperative outcomes in a series of patients included in a multimodal
      rehabilitation program (MMRP). METHODS: We analyzed a series of 104 patients that
      underwent elective surgery with primary anastomosis for rectal adenocarcinoma
      using a MMRP: 66 men and 38 women, with a median age of 64 (IQR: 55-75) years.
      Group A included patients with an associated loop ileostomy, and Group B, those
      without a protective stoma. RESULTS: Group A = 58, group B = 46 patients without
      differences in age, ASA, BMI and other risk factors, nor in the surgical approach
      (laparoscopic in 34%), although there were more neoadjuvant treatments in group
      A: 77.5 vs. 36.9%; P=.001. In group A, the most common operation was total
      mesorectal excision (96%) and in the B, a subtotal mesorectal excision (90%).
      There were no differences in postoperative complications (Group A 34.4 vs. group
      B28.2%; P=.322), anastomotic leaks (8.3 vs. 10.8%; P=.475), or postoperative
      ileus (20.7 vs. 10.9%; P=.140), neither in postoperative stay (7.9 vs. 6.9 days;
      P= .058, readmissions (7 vs. 13.6%; P= .22), or postoperative stay, including
      readmissions (8.4 vs. 9.1 days; P= .49). CONCLUSIONS: The association of a loop
      ileostomy does not extend the length of stay nor increases the rate of
      complications in patients that underwent a rectal resection with anastomosis
      included in a MMRP.

PMID- 24874997
TI  - Refractive changes after lens-sparing vitrectomy for rhegmatogenous retinal
      detachment.
AB  - PURPOSE: To evaluate refractive changes after lens-sparing vitrectomy for
      rhegmatogenous retinal detachment (RD). DESIGN: Retrospective case series.
      METHODS: A retrospective chart review was conducted in 66 eyes of 66 patients
      (50.0 +/- 9.9 years old) who had undergone lens-sparing vitrectomy for
      rhegmatogenous RD. Spherical equivalent refractive power was evaluated before and
      1, 2, 3, 6, 9, 12, and 15 months after vitrectomy. The relation between
      refractive changes and several parameters was investigated, such as axial length,
      presence of preoperative hemorrhage, preoperative spherical equivalent, retinal
      tear size, logMAR best-corrected visual acuity, number of laser
      photocoagulations, occurrence of postoperative vitreous hemorrhage, and degree of
      postoperative inflammatory reaction. Surgical parameters examined included
      operative time, wide-angle viewing system use, intraoperative adjuvant and gas
      tamponade use, vitrectomy system gauge, and surgeon. RESULTS: Significant and
      continuous myopic shift was observed after vitrectomy throughout the study
      period. Spherical equivalent was not significantly different between the operated
      eyes and the fellow control eyes until 3 months after vitrectomy, but the
      operated eyes were significantly more myopic at 3 months and later
      postoperatively (P < .05). Of the 58 eyes finally included (8 patients lost to
      follow-up), 27 (47%) underwent cataract surgery after vitrectomy. Patients who
      underwent cataract surgery were significantly older than those who did not (P <
      .05); no other examined parameter was significantly different between groups.
      CONCLUSIONS: A significant myopic progression occurred in eyes after lens-sparing
      vitrectomy for rhegmatogenous RD. A considerable amount of anisometropia
      occurred, even in the early postoperative period. Patient age was the only risk
      factor with the potential to advance the nuclear sclerotic cataract progression
      after vitrectomy.

PMID- 24874998
TI  - Foveal structure-function correlation in children with history of retinopathy of
      prematurity.
AB  - PURPOSE: To correlate visual acuity to macular spectral-domain optical coherence
      tomography (SD OCT) anomalies detected in children with a history of retinopathy
      of prematurity (ROP). DESIGN: Retrospective cohort study. METHODS: All charts of
      children with a history of ROP between 2 and 18 years of age and with SD OCT
      performed between 2010 and 2012 were reviewed. Central foveal thickness was
      measured and correlated with visual acuity. Secondary outcome measures included
      temporal parafoveal thickness, presence of the inner nuclear layer and outer
      segment, gestational age at birth, sex, spherical equivalent, history of laser
      treatment, and developmental delay. RESULTS: The study included 44 better-seeing
      eyes of 44 patients. Sixty-four percent (28/44) of patients in our study had
      20/40 or better visual acuity despite an abnormal foveal morphology in 91% of
      total eyes. CONCLUSION: Patients with a history of ROP demonstrate a high
      frequency of macular morphologic abnormalities, including retention of inner
      retinal layers and absent foveal depression, on SD OCT. These structural changes
      do not always correlate to visual acuity. Instead it appears that cone maturation
      may be a better indicator of visual acuity. In addition, there is a significant
      correlation between best-corrected visual acuity and myopia.

PMID- 24875000
TI  - Long-term increase in subfoveal choroidal thickness after surgery for senile
      cataracts.
AB  - PURPOSE: To evaluate the impact of cataract surgery on subfoveal choroidal
      thickness and central retinal thickness in the elderly. DESIGN: Prospective
      observational case series. METHODS: This cohort study included 29 eyes of 29
      patients with senile cataract, but no previous ocular surgery or other ocular
      abnormality. All 29 eyes received standard surgery by phacoemulsification and
      intraocular lens implantation. Subfoveal choroidal thickness and central retinal
      thickness were measured at baseline and 1, 3, and 6 months postoperatively by
      spectral-domain optical coherence tomography. Multiple regression analysis was
      conducted to identify predictors of larger changes in subfoveal choroidal
      thickness, including sex, age, baseline choroidal thickness, axial length,
      refractive status before surgery, and duration of surgery. RESULTS: The 29
      patients with senile cataract received cataract surgery without complication.
      Mean subfoveal choroidal thickness was 193.8, 208.9, 210.2, and 209.3 MUm at
      baseline and at postoperative 1, 3, and 6 months, respectively, with a
      statistically significant increase after surgery (repeated-measures ANOVA; P <
      .0001). In 20 eyes (69.0%), subfoveal choroidal thickness remained high even 6
      months after surgery. Multiple regression analysis revealed that male sex (P =
      .014) and thicker baseline choroid (P = .0048) predicted larger increases in
      subfoveal choroidal thickness. In contrast, the tendency of transient increase in
      central retinal thickness was not statistically significant. CONCLUSION: Most
      elderly patients with senile cataracts are expected to maintain increased
      subfoveal choroidal thickness for at least 6 months after cataract surgery.

PMID- 24874999
TI  - Bleb revision for resolution of hypotony maculopathy following primary
      trabeculectomy.
AB  - PURPOSE: To describe a surgical method of bleb revision for hypotony maculopathy,
      to evaluate its long-term efficacy, and to define the relationship between the
      duration of hypotony maculopathy and visual acuity (VA) outcomes. DESIGN:
      Noncomparative retrospective case series. METHODS: Medical records of 33 patients
      with hypotony maculopathy who underwent primary bleb revision between June 1999
      and September 2012 by a single surgeon at an academic medical center were
      reviewed. Hypotony maculopathy was characterized by the presence of a decrease in
      VA, retinal striae, and macular edema in the setting of decreased intraocular
      pressure (IOP) after glaucoma filtering surgery. The main outcome measure was
      final logMAR VA after bleb revision at 6 and 12 months. RESULTS: Thirty-three
      eyes of 33 patients were followed for 4.68 +/- 3.56 years (range 0.55-12.69
      years). Mean duration of hypotony maculopathy was 4.98 +/- 8.93 months. LogMAR VA
      improved from 0.78 +/- 0.40 at baseline to 0.34 +/- 0.34 (P < .001) 6 months
      after bleb revision and to 0.45 +/- 0.55 (P < .001) 12 months after bleb
      revision. Spearman rank coefficient (rs) correlating duration of hypotony and
      BCVA at both 6 and 12 months was significant (P = .015 and rs = 0.426, P = .028
      and rs = 0.416, respectively). Mean IOP increased from 3.51 +/- 2.27 mm Hg to
      12.06 +/- 4.06 mm Hg (P < .001) at 12 months. Fifty-two percent were on no
      antiglaucoma medications at last follow-up. Five eyes (15%) required a second
      bleb revision to correct persistent hypotony maculopathy. CONCLUSION: Surgical
      repair for hypotony maculopathy provided a significant improvement in VA at 6 and
      12 months. Surgical bleb revision is associated with good long-term control of
      IOP and improved VA in eyes with hypotony maculopathy after previous glaucoma
      filtering surgery.

PMID- 24875001
TI  - The outcomes of primary pediatric keratoplasty in Singapore.
AB  - PURPOSE: To evaluate the long-term corneal graft survival and risk factors for
      graft failure in pediatric eyes. DESIGN: Retrospective, interventional
      consecutive case series. METHODS: Unilateral eyes of 105 patients aged 16 years
      and below were included from the Singapore Corneal Transplant Study between April
      4, 1991 and April 4, 2011. Corneal graft survival was calculated using Kaplan
      Meier survival analysis, and survival distributions were compared using log-rank
      test. RESULTS: Mean recipient age was 8.38 +/- 5.63 years (range 0.18-15.92
      years). Mean follow-up time was 34.16 +/- 39.10 months. Main diagnoses were
      corneal scar (22.9%), limbal dermoid (21.9%), anterior segment dysgenesis
      (15.2%), and keratoconus (14.3%). Forty-four eyes (41.9%) underwent penetrating
      keratoplasty (PK), 37 (35.2%) underwent anterior lamellar keratoplasty (ALK), 22
      (21.0%) underwent lamellar corneal patch graft, and 2 (1.9%) underwent Descemet
      stripping automated endothelial keratoplasty (DSAEK). Kaplan-Meier survival rates
      for PK were 92.8% at 1 year, 88.9% at 2-4 years, and 80.9% at 5-16 years;
      survival rates for ALK were 88.0% at 1 year and 84.3% at 2-7 years; survival
      rates for corneal patch graft were 100% at 1-3 years and 90% at 4-10 years; these
      were not statistically significant (P = .362). Deep corneal vascularization (P =
      .012), preexisting active inflammation (P = .023), preexisting glaucoma drainage
      device (P = .023), and preexisting ocular surface disease (P = .037) were
      associated with reduced graft survival in a univariate analysis. CONCLUSIONS: We
      report good long-term graft survival following pediatric keratoplasty for various
      indications. Lamellar keratoplasty, when indicated, should be the procedure of
      choice in high-risk keratoplasties.

PMID- 24875002
TI  - Tattoo-associated uveitis.
AB  - PURPOSE: To describe the clinical presentation of uveitis with coincident onset
      of raised and indurated tattooed skin. DESIGN: Case series. METHODS: Seven
      consecutive patients were evaluated at a tertiary ophthalmologic facility with
      coincident uveitis and cutaneous tattoo induration over an 18-month period. All
      subjects underwent complete ophthalmic examination and a focused systemic medical
      evaluation including serologic testing and imaging studies. Two participants
      underwent biopsy of their tattoos. The patients' clinical courses and responses
      to treatment over a follow-up period of 1-20 months are reported (mean follow-up
      = 9 months). Main outcome measures included degree of intraocular inflammation,
      ocular complications, visual acuity, clinically observable tattooed skin changes,
      and biopsy results. RESULTS: Five of 7 patients had bilateral nongranulomatous
      anterior uveitis: 4 with chronic and 1 with recurrent disease. The remaining 2
      patients had bilateral chronic granulomatous panuveitis. Biopsies of raised and
      indurated tattoos were performed in 2 patients and demonstrated noncaseating
      granulomatous inflammation surrounding tattoo ink in the dermis. The skin changes
      resolved in all patients, with a faster response noted in those treated with high
      dose oral prednisone for intraocular inflammation. Five patients subsequently
      experienced recurrent flares of intraocular inflammation in conjunction with the
      recurrence of raised and indurated tattoos. CONCLUSIONS: These cases represent a
      subset of patients in whom skin tattooing may have incited an immune response
      leading to simultaneous inflammation of the eyes and tattooed skin.

PMID- 24875004
TI  - Structural elucidation of humulone autoxidation products and analysis of their
      occurrence in stored hops.
AB  - The transformation of alpha-acids [in hops (Humulus lupulus L.)] to iso-alpha
      acids (in beer) during the brewing process is well known, but the occurrence and
      structure of the oxidized alpha-acids during hop storage are not well documented.
      Because an understanding of these oxidized compounds is essential to optimize the
      effects of oxidized hops on the quality of beer, we investigated the autoxidation
      products of humulone (a representative congener of alpha-acids) using a
      simplified autoxidation model. Among the oxidation products,
      tricyclooxyisohumulones A (1) and B (2), tricycloperoxyisohumulone A (3),
      deisopropyltricycloisohumulone (4), and the hemiacetal 5 of
      tricycloperoxyhumulone A (5') were isolated, and their structures were elucidated
      for the first time. The occurrence of compounds 1-4 in stored hops was verified
      using LC/MS/MS analysis. We also monitored the levels of compounds 1-4 during hop
      storage using LC/MS/MS analysis. 

PMID- 24875003
TI  - Bacterial proteins and peptides in cancer therapy: today and tomorrow.
AB  - Cancer is one of the most deadly diseases worldwide. In the last three decades
      many efforts have been made focused on understanding how cancer grows and
      responds to drugs. The dominant drug-development paradigm has been the "one drug,
      one target." Based on that, the two main targeted therapies developed to combat
      cancer include the use of tyrosine kinase inhibitors and monoclonal antibodies.
      Development of drug resistance and side effects represent the major limiting
      factors for their use in cancer treatment. Nowadays, a new paradigm for cancer
      drug discovery is emerging wherein multi-targeted approaches gain ground in
      cancer therapy. Therefore, to overcome resistance to therapy, it is clear that a
      new generation of drugs is urgently needed. Here, regarding the concept of multi
      targeted therapy, we discuss the challenges of using bacterial proteins and
      peptides as a new generation of effective anti-cancer drugs. 

PMID- 24875006
TI  - Localized nano-solid-solution induced by Cu doping in ZnS for efficient solar
      hydrogen generation.
AB  - Nanosized photocatalysts have been shown to be important to many modern
      photocatalytic reactions. Control of the microstructure of the nanocrystals
      enables regulation of their optical properties and enhancement of specific
      reactions. Here, Cu(2+)-doped ZnS nanosphere photocatalysts with hierarchical
      nanostructures and controllable sizes were synthesized via a facile wet-chemical
      reaction. We demonstrated that small amounts of Cu(2+) doping could give rise to
      the formation of a variety of localized, nanosized Cu(1-x)Zn(x)S solid solutions
      that are separated by a continuous ZnS medium. The nano-solid-solutions have
      predictable band structures and an average size of several nanometers, which
      ensure facile generation of electron-hole pairs by visible light irradiation and
      quick migration of the photo-generated charges to the interfaces. With Ru as a
      cocatalyst, the as-prepared 0.5 mol% Cu(2+)-doped ZnS nanospheres showed a high
      H2 evolution rate of 1.03 mmol h(-1), corresponding to a quantum efficiency of
      26.2% at 425 nm. A hierarchical surface structure with a large surface area is
      considered crucial for the increased activity. Our work not only showed that the
      non-toxic metal chalcogenides achieve high efficiency but also provides a new
      concept of localized nano-solid-solution for photocatalytic applications.

PMID- 24875005
TI  - Liposomal inhibition of acrolein-induced injury in rat cultured urothelial cells.
AB  - PURPOSE: To study the protection offered by empty liposomes (LPs) alone against
      acrolein-induced changes in urothelial cell viability and explored uptake of LPs
      by primary (rat) urothelial cells. METHODS: Acrolein was used as a means to
      induce cellular damage and reduce urothelial cellular viability. The effect of
      acrolein or liposomal treatment on cellular proliferation was studied using 5
      bromo-2'-deoxy-uridine assay. Cytokine release was measured after urothelial
      cells were exposed to acrolein. Temperature-dependent uptake study was carried
      out for fluorescent-labeled LPs using confocal microscopy. RESULTS: Liposome
      pretreatment protected against acrolein-induced decrease in urothelial cell
      proliferation. LPs also significantly affected the acrolein-induced cytokine
      (interferon-gamma) release offering protection to the urothelial cells against
      acrolein damage. We also observed a temperature-dependent urothelial uptake of
      fluorescent-labeled LPs occurred at 37  degrees C (but not at 4  degrees C).
      CONCLUSIONS: Empty LPs alone provide a therapeutic efficacy against acrolein
      induced changes in urothelial cell viability and may be a promising local therapy
      for bladder diseases. Hence, our preliminary evidence provides support for
      liposome-therapy for urothelial protection and possible repair.

PMID- 24875007
TI  - The conserved miR-8/miR-200 microRNA family and their role in invertebrate and
      vertebrate neurogenesis.
AB  - Since their discovery in the early 1990s, microRNAs have emerged as key
      components of the post-transcriptional regulation of gene expression. MicroRNAs
      occur in the plant and animal kingdoms, with the numbers of microRNAs encoded in
      the genome increasing together with the evolutionary expansion of the phyla. By
      base-pairing with complementary sequences usually located within the 3'
      untranslated region, microRNAs target mRNAs for degradation, destabilization
      and/or translational inhibition. Because one microRNA can have many, if not
      hundreds, of target mRNAs and because one mRNA can, in turn, be targeted by many
      microRNAs, these small single-stranded RNAs can exert extensive pleiotropic
      functions during the development, adulthood and ageing of an organism. Specific
      functions of an increasing number of microRNAs have been described for the
      invertebrate and vertebrate nervous systems. Among these, the miR-8/miR-200
      microRNA family has recently emerged as an important regulator of neurogenesis
      and gliogenesis and of adult neural homeostasis in the central nervous system of
      fruit flies, zebrafish and rodents. This highly conserved microRNA family
      consists of a single ortholog in the fruit fly (miR-8) and five members in
      vertebrates (miR-200a, miR-200b, miR-200c, miR-141 and miR-429). Here, we review
      our current knowledge about the functions of the miR-8/miR-200 microRNA family
      during invertebrate and vertebrate neural development and adult homeostasis and,
      in particular, about their role in the regulation of neural stem/progenitor cell
      proliferation, cell cycle exit, transition to a neural precursor/neuroblast
      state, neuronal differentiation and cell survival and during glial cell growth
      and differentiation into mature oligodendrocytes. 

PMID- 24875008
TI  - Protective effect of chitin and chitosan enriched diets on immunity and disease
      resistance in Cirrhina mrigala against Aphanomyces invadans.
AB  - The effect of diet enriched with 1% chitin or chitosan on innate immune response
      and disease resistance in Cirrhina mrigala against Aphanomyces invadans was
      investigated at weeks 1, 2, and 4. In the un-infected and infected groups the
      white blood cells (WBC), red blood cells (RBC), haematocrit (Ht), lympocytes,
      monocytes, and neutrophils significantly increased when fed with 1% chitin (CH)
      or chitosan (CT) enriched diet from weeks 1 to 4 when compared to control;
      however, the haemoglobin (Hb) and thrombocytes significantly increased only on
      weeks 2 and 4. The total protein and albumin levels also significantly increased
      with any enriched diet on weeks 2 and 4; but the globulin and albumin:globulin
      ratio increased on week 4 as compared to control; similarly the phagocytic
      activity significantly increased on weeks 2 and 4 while the lysozyme activity
      increased from weeks 1 to 4. The complement activity was significantly enhanced
      in CT and CTI fed groups on weeks 2 and 4. In un-infected fish fed with 1% CH and
      CT diets, the cumulative mortality was 10% and 5% whereas the infected fish
      suffered 20% and 25% mortality. The present results suggest that infected fish
      fed with 1% chitin or chitosan enriched diet modulates the immune system
      conferring disease resistance in C. mrigala against A. invadans.

PMID- 24875009
TI  - Evaluation of the impact of camelina oil-containing diets on the expression of
      genes involved in the innate anti-viral immune response in Atlantic cod (Gadus
      morhua).
AB  - To improve sustainability of aquaculture, especially for carnivorous species like
      Atlantic cod, replacement of fish oil-based diets with vegetable oil-based diets
      has been studied. The use of vegetable oil in fish feeds can significantly change
      the fatty acid composition of fish tissues, and given the importance of fatty
      acids in inflammation and immunity, this change could potentially impact the
      immune response and health of the fish. The oilseed Camelina sativa is a
      promising source for this vegetable oil, because of the high oil content of its
      seeds (40%), a higher n-3 fatty acid content than most other oilseeds, and a high
      amount of gamma-tocopherol. This study aims to investigate the effect of the
      replacement of dietary fish oil with oil from Camelina sativa on the immune
      response of Atlantic cod, as measured by the gene expression in spleen. Juvenile
      cod were fed on a fish oil-based diet (FO) or one of two diets in which camelina
      oil replaced 40% or 80% of fish oil (40CO and 80CO respectively) for 67 days,
      after which they were injected with either the viral mimic polyriboinosinic
      polyribocytidylic acid (pIC), or phosphate-buffered saline (PBS) as a control.
      Microarray analysis was used to determine the effect of the diet on the basal
      spleen transcriptome (pre-injection), and on the response to pIC (24 h post
      injection). No marked differences in the spleen transcriptome were found between
      the three diets, either before or after injection with pIC. All fish, regardless
      of diet, showed a strong anti-viral response 24 h after pIC injection, with more
      than 500 genes having a significant difference of expression of 2-fold or higher
      compared to the PBS-injected fish for the FO, 40CO and 80CO diets. Gene Ontology
      annotation analysis of the three pIC-responsive gene lists indicated they were
      highly similar, and that the term 'immune system process' was significantly
      enriched in the pIC-responsive gene lists for all three diets. QPCR analysis for
      5 genes with a known function in the anti-viral innate immune response (LGP2,
      STAT1, IRF1, ISG15 and viperin) showed modestly (smaller than 2-fold) up
      regulated basal expression of LGP2, IRF1 and STAT1 in fish fed 40CO compared to
      the other diets. After pIC injection, all 5 genes were significantly and strongly
      up-regulated in pIC-injected fish compared to PBS-injected fish, but no
      significant differences were found between any of the diets. In conclusion,
      replacement of up to 80% of fish oil with camelina oil in Atlantic cod diets does
      not have a strong effect on basal spleen gene expression. Atlantic cod fed on
      camelina oil-containing diets are capable of mounting a strong anti-viral immune
      response, which is comparable to that in cod fed with a fish oil diet. 

PMID- 24875010
TI  - Rock bream (Oplegnathus fasciatus) IL-12p40: identification, expression, and
      effect on bacterial infection.
AB  - IL-12p40, also called IL-12beta, is a subunit of the proinflammatory cytokines
      interleukin (IL)-12 and IL-23. In teleost, IL-12p40 homologues have been
      identified in several species, however, the biological function of fish IL-12p40
      is essentially unknown. In this work, we reported the identification and analysis
      of an IL-12p40, OfIL-12p40, from rock bream (Oplegnathus fasciatus). OfIL-12p40
      is composed of 361 amino acids and possesses a conserved IL-12p40 domain and a
      WSxWS signature motif characteristic of known IL-12p40. Constitutive expression
      of OfIL-12p40 occurred in multiple tissues and was highest in kidney.
      Experimental infection with bacterial pathogen upregulated the expression of OfIL
      12p40 in kidney and spleen in a time-dependent manner. Purified recombinant OfIL
      12p40 (rOfIL-12p40) stimulated the respiratory burst activity of peripheral blood
      leukocytes in a dose-dependent manner. rOfIL-12p40 also enhanced the resistance
      of rock bream against bacterial infection and upregulated the expression of
      innate immune genes in kidney. Taken together, these results indicate that OfIL
      12p40 possesses cytokine-like property and plays a role in immune defense against
      bacterial infection.

PMID- 24875011
TI  - Commentary: changing paradigms in the oral disease-systemic disease relationship.

PMID- 24875012
TI  - Letter to the editor: re: update of the case definitions for population-based
      surveillance of periodontitis.

PMID- 24875013
TI  - Letter to the editor: authors' response.

PMID- 24875017
TI  - A highly efficient oxidative condensation reaction for selective protein
      conjugation.
AB  - We hereby report a mild and efficient coupling reaction between alkyl aldehydes
      and aryl diamines. In the presence of a Cu(2+) or a Zn(2+) ion, oxygen (O2) in
      air is able to promote the oxidative condensation of the two readily preparable
      functional groups, forming stable benzimidazole linkages in neutral aqueous
      solution at room temperature (RT). We demonstrated that the reaction could be
      utilized to label a T4 lysozyme protein containing a chemically installed aryl
      diamine group with a fluorescent aldehyde dye molecule at 37  degrees C. 

PMID- 24875018
TI  - Co-occurring gland angularity in localized subgraphs: predicting biochemical
      recurrence in intermediate-risk prostate cancer patients.
AB  - Quantitative histomorphometry (QH) refers to the application of advanced
      computational image analysis to reproducibly describe disease appearance on
      digitized histopathology images. QH thus could serve as an important
      complementary tool for pathologists in interrogating and interpreting cancer
      morphology and malignancy. In the US, annually, over 60,000 prostate cancer
      patients undergo radical prostatectomy treatment. Around 10,000 of these men
      experience biochemical recurrence within 5 years of surgery, a marker for local
      or distant disease recurrence. The ability to predict the risk of biochemical
      recurrence soon after surgery could allow for adjuvant therapies to be prescribed
      as necessary to improve long term treatment outcomes. The underlying hypothesis
      with our approach, co-occurring gland angularity (CGA), is that in benign or less
      aggressive prostate cancer, gland orientations within local neighborhoods are
      similar to each other but are more chaotically arranged in aggressive disease. By
      modeling the extent of the disorder, we can differentiate surgically removed
      prostate tissue sections from (a) benign and malignant regions and (b) more and
      less aggressive prostate cancer. For a cohort of 40 intermediate-risk (mostly
      Gleason sum 7) surgically cured prostate cancer patients where half suffered
      biochemical recurrence, the CGA features were able to predict biochemical
      recurrence with 73% accuracy. Additionally, for 80 regions of interest chosen
      from the 40 studies, corresponding to both normal and cancerous cases, the CGA
      features yielded a 99% accuracy. CGAs were shown to be statistically signicantly
      ([Formula: see text]) better at predicting BCR compared to state-of-the-art QH
      methods and postoperative prostate cancer nomograms. 

PMID- 24875020
TI  - Total knee arthroplasty after previous knee surgery: expected interval and the
      effect on patient age.
AB  - BACKGROUND: With more than 650,000 knee arthroscopies and 175,000 anterior
      cruciate ligament reconstructions performed annually in the United States,
      patients presenting for total knee arthroplasty are increasingly likely to have
      had previous knee surgery. The purpose of this study was to assess the prevalence
      of previous knee surgery in patients undergoing total knee arthroplasty and to
      test the hypothesis that patients with previous knee surgery undergo total knee
      arthroplasty at a younger age. METHODS: All patients undergoing primary total
      knee arthroplasty over the study period who consented to enroll in a prospective
      total joint registry were reviewed. Inclusion criteria included a diagnosis of
      osteoarthritis or posttraumatic arthritis. RESULTS: Of 1372 patients in the
      registry, 1286 met inclusion criteria. Twenty-nine percent had a history of knee
      surgery, and significantly more men (39%) than women (24%) had a history of knee
      surgery (p < 0.0001). Patients with previous knee surgery were significantly
      younger (p < 0.0001) at total knee arthroplasty; the mean age (and standard
      deviation) was 59 +/- 10 years for patients with previous knee surgery compared
      with 66.6 +/- 10.4 years for patients without previous knee surgery. Patients
      with a history of ligament reconstruction underwent total knee arthroplasty at a
      significantly younger age (p < 0.0001) than patients with a history of other knee
      surgery; the mean age (and standard deviation) was 50.2 +/- 9.1 years for
      patients with a history of ligament reconstruction and 59.9 +/- 9.6 years for
      patients with a history of other knee surgery. Among patients who had not
      undergone previous knee surgery, women underwent total knee arthroplasty at a
      significantly younger age (p < 0.001) than men; the mean age (and standard
      deviation) was 65.4 +/- 10.3 years for women and 69.3 +/- 10 years for men.
      However, there was no difference in age between the sexes in those with previous
      knee surgery; the mean age (and standard deviation) was 58.6 +/- 10.1 years for
      women and 59.6 +/- 9.8 years for men. The average interval (and standard
      deviation) from previous knee surgery to total knee arthroplasty is 13.1 +/- 12.6
      years, longer in men (17.7 +/- 13.8 years) than in women (9.1 +/- 9.8 years) (p <
      0.0001). CONCLUSIONS: Patients with previous knee surgery undergo total knee
      arthroplasty at a significantly younger age than patients without previous knee
      surgery, especially men and patients with a history of ligament reconstruction.
      This may be a factor in the rising demand for total knee arthroplasty. Future
      investigation to identify those at risk for early total knee arthroplasty after
      knee surgery and to develop methods to delay or to prevent the need for future
      total knee arthroplasty in these patients is warranted. LEVEL OF EVIDENCE:
      Prognostic Level III. See Instructions for Authors for a complete description of
      levels of evidence.

PMID- 24875019
TI  - Symptoms of pain do not correlate with rotator cuff tear severity: a cross
      sectional study of 393 patients with a symptomatic atraumatic full-thickness
      rotator cuff tear.
AB  - BACKGROUND: For many orthopaedic disorders, symptoms correlate with disease
      severity. The objective of this study was to determine if pain level is related
      to the severity of rotator cuff disorders. METHODS: A cohort of 393 subjects with
      an atraumatic symptomatic full-thickness rotator-cuff tear treated with physical
      therapy was studied. Baseline pretreatment data were used to examine the
      relationship between the severity of rotator cuff disease and pain. Disease
      severity was determined by evaluating tear size, retraction, superior humeral
      head migration, and rotator cuff muscle atrophy. Pain was measured on the 10
      point visual analog scale (VAS) in the patient-reported American Shoulder and
      Elbow Surgeons (ASES) score. A linear multiple regression model was constructed
      with use of the continuous VAS score as the dependent variable and measures of
      rotator cuff tear severity and other nonanatomic patient factors as the
      independent variables. Forty-eight percent of the patients were female, and the
      median age was sixty-one years. The dominant shoulder was involved in 69% of the
      patients. The duration of symptoms was less than one month for 8% of the
      patients, one to three months for 22%, four to six months for 20%, seven to
      twelve months for 15%, and more than a year for 36%. The tear involved only the
      supraspinatus in 72% of the patients; the supraspinatus and infraspinatus, with
      or without the teres minor, in 21%; and only the subscapularis in 7%. Humeral
      head migration was noted in 16%. Tendon retraction was minimal in 48%, midhumeral
      in 34%, glenohumeral in 13%, and to the glenoid in 5%. The median baseline VAS
      pain score was 4.4. RESULTS: Multivariable modeling, controlling for other
      baseline factors, identified increased comorbidities (p = 0.002), lower education
      level (p = 0.004), and race (p = 0.041) as the only significant factors
      associated with pain on presentation. No measure of rotator cuff tear severity
      correlated with pain (p > 0.25). CONCLUSIONS: Anatomic features defining the
      severity of atraumatic rotator cuff tears are not associated with the pain level.
      Factors associated with pain are comorbidities, lower education level, and race.
      LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a
      complete description of levels of evidence.

PMID- 24875022
TI  - Autologous osteochondral transplantation for treating patellar chondral injuries:
      evaluation, treatment, and outcomes of a two-year follow-up study.
AB  - BACKGROUND: The patella is the largest human sesamoid bone and often sustains
      chondral injury. There is no consensus on how to treat a full-thickness,
      symptomatic articular cartilage injury of the patella. We analyzed the clinical
      and functional outcomes of patients with symptomatic full-thickness patellar
      chondral lesions treated with autologous osteochondral transplantation and
      evaluated osteochondral autograft bone-plug integration through magnetic
      resonance imaging. METHODS: In this prospective study, thirty-three patients with
      a symptomatic full-thickness patellar chondral injury surgically treated with
      autologous osteochondral transplantation were evaluated before and after surgical
      treatment with a minimum two-year follow-up using the Lysholm, Kujala, and
      Fulkerson questionnaires and the Short Form-36 health survey score. Magnetic
      resonance images were made at six and twelve months postoperatively and studies
      were performed to analyze the osteochondral autograft bone-plug integration.
      RESULTS: All thirty-three patients showed a significant improvement in functional
      scores two years after surgery. The average Lysholm scores were 57.27 points
      preoperatively and 80.76 points at two years postoperatively, the average Kujala
      scores were 54.76 points preoperatively and 75.18 points at two years
      postoperatively, and the Fulkerson average scores were 54.24 points
      preoperatively and 80.42 points at two years postoperatively. The Short Form-36
      life quality score improved significantly. Two years after surgery, all magnetic
      resonance images showed full bone-plug integration into the patella. CONCLUSIONS:
      Autologous osteochondral transplantation is a successful technique to surgically
      treat symptomatic full-thickness patellar articular cartilage injuries smaller
      than 2.5 cm in diameter. Patients had a significant improvement in clinical
      scores. Bone-plug integration and surface alignment were demonstrated in all
      patients two years after surgery. LEVEL OF EVIDENCE: Therapeutic Level IV. See
      Instructions for Authors for a complete description of levels of evidence.

PMID- 24875021
TI  - The impact of depression and pain catastrophization on initial presentation and
      treatment outcomes for atraumatic hand conditions.
AB  - BACKGROUND: Prior studies have suggested that patient-rated hand function is
      impacted by depression and pain catastrophization. We studied the impact that
      these comorbidities have on treatment outcomes. METHODS: Two hundred and fifty
      six patients presenting to an orthopaedic hand clinic were followed in this
      prospective cohort investigation. Patients who were prescribed treatment for
      atraumatic hand/wrist conditions were eligible for inclusion. At enrollment, all
      patients completed the Center for Epidemiologic Studies Depression (CES-D) scale,
      the Pain Catastrophizing Scale (PCS), and the Michigan Hand Outcomes
      Questionnaire (MHQ; scale of 0 to 100, with 100 indicating the best hand
      performance). One month and three months after treatment, patients again
      completed the MHQ. Participants' psychological comorbidity status was categorized
      as either affected (a CES-D score of >=16, indicating depression, or a PCS score
      of >=30, indicating catastrophization) or unaffected (a CES-D score of <16 and a
      PCS score of <30). Diagnoses and treatments for both the affected and unaffected
      groups were examined. The effect of time and patient status, and their
      interaction, on MHQ scores was evaluated by mixed modeling. RESULTS: Fifty
      patients were categorized as affected and 206 as unaffected. Diagnoses and
      treatments differed minimally between the two groups. At the time of enrollment,
      the mean MHQ score of the unaffected group (64.9; 95% confidence interval [CI],
      62.5 to 67.3) was significantly higher than that of the affected group (48.1; 95%
      CI, 43.3 to 53.0). Both groups demonstrated similar significant absolute
      improvement over baseline at three months after treatment (an increase of 12.5
      points [95% CI, 7.5 to 17.4] in the affected group and 12.8 points [95% CI, 10.4
      to 15.3] in the unaffected group). Thus, at the time of final follow-up, the
      rating of hand function by the affected patients (60.6 [95% CI, 55.0 to 66.2])
      was still significantly poorer than the rating by the unaffected patients (77.7
      [95% CI, 75.0 to 80.5]). CONCLUSIONS: Although patients affected by depression
      and/or pain catastrophization reported worse self-rated hand function at baseline
      and at the time of follow-up, these patients showed similar absolute improvement
      in self-rated hand function following treatment compared with patients with
      unaffected status. LEVEL OF EVIDENCE: Prognostic Level I. See Instructions for
      Authors for a complete description of levels of evidence.

PMID- 24875023
TI  - Autologous chondrocyte implantation in the knee: mid-term to long-term results.
AB  - BACKGROUND: From 1998 to 2008, 1000 skeletally mature patients underwent
      autologous chondrocyte implantation for an osteochondral defect of the knee. We
      evaluated the functional outcomes in 827 of 869 patients who had undergone
      autologous chondrocyte implantation with Chondron or periosteum (ACI-C/ACI-P) or
      matrix-assisted chondrocyte implantation (MACI) and attempted to identify factors
      that influenced outcome. METHODS: The age of the patient, the size and site of
      the osteochondral lesion, previous surgery, and the presence of early
      osteoarthritis were assessed for their influence on outcomes. Each factor was
      evaluated in a separate Cox proportional hazards model with use of hazard ratios
      (HRs), with 95% confidence intervals (CIs), describing the likelihood of failure
      for that particular factor. Outcomes were assessed with use of the modified
      Cincinnati score, visual analog scale pain score, and Stanmore functional score.
      RESULTS: The mean duration of follow-up was 6.2 years (range, two to twelve
      years). The mean age was thirty-four years (range, fourteen to fifty-six years),
      with 493 males and 334 females. The average size of the defect was 409 mm2
      (range, 64 to 2075 mm2). Four hundred and twenty-one procedures (51%) were
      performed on the medial femoral condyle; 109 (13%), on the lateral femoral
      condyle; 200 (24%), on the patella; and fifty (6%), on the trochlea. Kaplan-Meier
      survival analysis revealed that the unadjusted graft survival rate was 78.2% at
      five years and 50.7% and ten years for the entire cohort. No difference was found
      between the survival rates of the ACI-C/ACI-P and MACI techniques (HR = 0.948,
      95% CI = 0.738 to 1.219, p = 0.678). There was a significant postoperative
      improvement in the function and pain scores of all three outcome measures (p <
      0.002). Survivorship in the group with a previous cartilage regenerative
      procedure was inferior to that in patients with a previously untreated lesion,
      with failure five times more likely in the former group (HR = 4.718, standard
      error [SE] = 0.742, 95% CI = 3.466 to 6.420, p < 0.001). Degenerative change in
      any compartment had a significant detrimental effect on survivorship, with
      survivorship worsening as the osteoarthritis grade increased (Grade 1: HR =
      2.077, 95% CI = 1.299 to 3.322, p = 0.002; Grade 2: HR = 3.450, 95% CI = 2.646 to
      4.498, p < 0.001; and Grade 3: HR = 3.820, 95% CI = 2.185 to 6.677, p < 0.001).
      CONCLUSIONS: Our study demonstrated an overall graft survival of 78% at five
      years and 51% beyond ten years following both autologous chondrocyte implantation
      techniques. Despite study limitations, our results demonstrate that autologous
      chondrocyte implantation for the treatment of osteochondral defects of the knee
      can achieve good results. LEVEL OF EVIDENCE: Therapeutic Level IV. See
      Instructions for Authors for a complete description of levels of evidence.

PMID- 24875025
TI  - Outcomes and prognostic factors for Ewing-family tumors of the extremities.
AB  - BACKGROUND: There are few published studies describing the clinical results of
      patients uniformly treated for a Ewing-family tumor of an extremity. METHODS: We
      performed a review of patients who had received uniform treatment consisting of
      neoadjuvant chemotherapy, surgery and/or radiation therapy as local treatment,
      and then adjuvant chemotherapy from June 2003 to November 2011 at a single
      institution. RESULTS: There were 158 patients included in the study. The median
      age was fifteen years. Sixty-nine (44%) of the patients had metastatic disease at
      presentation. Fifty-seven patients underwent surgery, and forty-one received
      radical radiation therapy following neoadjuvant chemotherapy. After a median of
      24.3 months (range, 1.6 to ninety-seven months) of follow-up, the five-year event
      free survival, overall survival, and local control rates (and standard error)
      were 24.1% +/- 4.3%, 43.5% +/- 6%, and 55% +/- 6.8%, respectively, for the entire
      cohort and 36.4% +/- 6.2%, 57.6% +/- 7.4%, and 58.2% +/- 7.9%, respectively, for
      patients without metastases. In the multivariate analysis, metastases predicted
      inferior event-free survival (p = 0.02) and overall survival (p = 0.03) rates in
      the entire cohort, whereas radical radiation therapy predicted an inferior local
      control rate in the entire cohort (p = 0.001) and in patients without metastases
      (p = 0.04). In the group with localized disease, there was no difference between
      the patients who received radical radiation therapy and those who underwent
      surgery with regard to tumor diameter (p = 0.8) or post-neoadjuvant chemotherapy
      response (p = 0.1). A white blood cell count (WBC) of >11 * 109/L predicted
      inferior event-free survival (p = 0.005) and local control (p = 0.02) rates for
      patients without metastases. CONCLUSIONS: To our knowledge, this is the largest
      study on extremity Ewing-family tumors treated with uniform chemotherapy and
      either surgical resection or radical radiation therapy in Asia. All possible
      efforts should be made to resect a primary tumor after neoadjuvant chemotherapy,
      as radical radiation therapy alone results in a poor local control rate despite a
      good post-neoadjuvant chemotherapy response. Patients without metastases but with
      a high WBC had inferior event-free survival and local control rates and may
      require more aggressive therapy. LEVEL OF EVIDENCE: Therapeutic Level IV. See
      Instructions for Authors for a complete description of levels of evidence.

PMID- 24875026
TI  - A randomized, controlled, prospective study evaluating the effect of patellar
      eversion on functional outcomes in primary total knee arthroplasty.
AB  - BACKGROUND: Patellar mobilization technique during total knee arthroplasty has
      been debated, with some suggesting that lateral retraction, rather than eversion,
      of the patella may be beneficial. We hypothesized that patients with knees
      surgically exposed using patellar lateral retraction would have comparable
      outcomes with patients with knees surgically exposed using patellar eversion.
      METHODS: After an a priori power analysis, 120 patients with degenerative
      arthrosis were prospectively enrolled and were randomized to one of two patellar
      exposure techniques during the primary total knee arthroplasty: lateral
      retraction or eversion. The primary outcome measure was one-year, dynamometer
      measured quadriceps strength. The secondary outcome measures evaluated during
      hospital stay included the ability to straight-leg raise, visual analog scale in
      pain, walking distance, and length of stay. The secondary outcome measures that
      were evaluated preoperatively and through a one-year follow-up included the Short
      Form-36 Physical Component Summary and Mental Component Summary scores, range of
      motion, quadriceps strength, and radiographic rate of patella baja and tilt.
      RESULTS: A mixed-model analysis of variance showed no significant differences
      between the two groups in the one-year outcome measures. At one year
      postoperatively, quadriceps strength was not different between groups (p = 0.77),
      and the range of motion significantly improved (p < 0.01) from preoperative
      values by a mean value (and standard deviation) of 6 degrees  +/- 17 degrees ,
      with no significant difference (p = 0.60) between groups. The Short Form-36
      Physical Component Summary score and Mental Component Summary score significantly
      improved (p < 0.01) for both study groups from preoperatively to one year
      postoperatively with no significantly different effects between groups (time *
      group, p = 0.85 for the Physical Component Summary score and p = 0.71 for the
      Mental Component Summary score), and the scores were not different at one year
      after surgery. There were no significant differences between groups in the change
      in frequency of the radiographic patella baja (p = 0.99) or the radiographic
      patellar tilt (p = 0.77) from before surgery to one year after surgery.
      CONCLUSIONS: Lateral retraction of the patella did not lead to superior
      postoperative results compared with eversion of the patella during total knee
      arthroplasty as evaluated using our primary outcome measure of one-year,
      dynamometer-measured quadriceps strength or our secondary outcome measures. LEVEL
      OF-EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete
      description of levels of evidence.

PMID- 24875024
TI  - Neuropathy and poorly controlled diabetes increase the rate of surgical site
      infection after foot and ankle surgery.
AB  - BACKGROUND: This prospective study was designed to evaluate the frequency of
      surgical site infection in patients treated with foot and ankle surgery. Our
      hypothesis was that patients with complications of diabetes are at increased risk
      for surgical site infection compared with patients without diabetes and patients
      with diabetes who do not have diabetic complications. Another goal was to compare
      the association of neuropathy with surgical site infection in both nondiabetic
      and diabetic patients. METHODS: Two thousand and sixty consecutive surgical cases
      were evaluated. Group 1 included nondiabetic patients without neuropathy, Group 2
      included nondiabetic patients with neuropathy, Group 3 included patients with
      diabetes but no diabetic complications, and Group 4 included patients with
      diabetes who had at least one complication of diabetes. RESULTS: The surgical
      site infection rate in this study was 3.1%. Patients with complicated diabetes
      had a 7.25-fold increased risk of surgical site infection compared with
      nondiabetic patients without neuropathy and a 3.72-fold increased risk compared
      with patients with uncomplicated diabetes. Patients with complicated diabetes had
      a nonsignificant 1.54-fold higher rate of surgical site infection compared with
      nondiabetic patients with neuropathy. Nondiabetic patients with neuropathy had a
      significant 4.72-fold increased risk of surgical site infection compared with
      nondiabetic patients without neuropathy. Despite this, nondiabetic patients with
      neuropathy did not have a significantly higher rate of surgical site infection
      than patients with uncomplicated diabetes, and the frequency of surgical site
      infection in the group with uncomplicated diabetes was not significantly
      different from that in the nondiabetic patients without neuropathy. Multivariable
      logistic regression analysis demonstrated that peripheral neuropathy and a
      hemoglobin A1c of >=8% were independently associated with surgical site
      infection. CONCLUSIONS: Complicated diabetes increases the risk of surgical site
      infection after foot and ankle surgery. Patients who had diabetes without
      complications did not have a greater risk of surgical site infection compared
      with nondiabetic patients without neuropathy. The presence of neuropathy
      increases the risk of surgical site infection even in patients without diabetes.
      Poor long-term glycemic control is also associated with an increased risk of
      surgical site infection. LEVEL OF EVIDENCE: Prognostic Level I. See Instructions
      for Authors for a complete description of levels of evidence.

PMID- 24875027
TI  - Vein wrapping for chronic nerve constriction injury in a rat model: study showing
      increases in VEGF and HGF production and prevention of pain-associated behaviors
      and nerve damage.
AB  - BACKGROUND: Although efficacious clinical results have been reported after vein
      wrapping for the treatment of recurrent compressive neuropathy, the mechanism of
      nerve protection remains uncertain. METHODS: Eight-week-old male Wistar rats (n =
      90) were randomly divided into three groups: sham procedure, chronic constriction
      injury, and chronic constriction injury plus vein wrapping. Mechanical withdrawal
      thresholds and walking patterns were measured with use of von Frey filaments and
      the CatWalk system, respectively. We investigated L4-L5 dorsal root ganglia
      immunohistochemically at fourteen days postsurgery and sciatic nerves
      histologically at fourteen days and again five months postsurgery. Concentrations
      of several sciatic neurotrophic factors in the ligated sciatic nerves were
      quantified with use of ELISA (enzyme-linked immunosorbent assay). RESULTS: In
      behavioral tests, the rats in which the chronic constriction injury had been
      followed by vein wrapping displayed significantly greater pain responses than the
      sham group, and the group with untreated chronic constriction injury showed
      greater pain responses than the vein-wrapping group (both p < 0.05).
      Immunoreactive markers of inflammation and nerve damage, calcitonin gene-related
      peptide (CGRP) and activating transcription factor-3 (ATF3), were upregulated in
      dorsal root ganglion neurons in the constriction-injury and vein-wrapping groups
      compared with those in the sham group, with greater upregulation in the
      constriction-injury group than in the vein-wrapping group (both p < 0.01).
      Histologic observation showed marked nerve degeneration and scar tissue formation
      around the sciatic nerve in the constriction-injury group, but these effects were
      prevented to some extent in the vein-wrapping group. Vascular endothelial growth
      factor (VEGF) levels at one and three days postsurgery and hepatocyte growth
      factor (HGF) levels at three, seven, fourteen, and twenty-eight days postsurgery
      were significantly higher in the vein-wrapping group than in the other groups (p
      < 0.05). CONCLUSIONS: Vein wrapping decreased pain-associated behavior and nerve
      damage caused by chronic constriction injury. VEGF and HGF produced in response
      to vein grafts may play a mechanistic role. CLINICAL RELEVANCE: These findings
      may lead to development of new therapies employing growth factors, with or
      without other materials, that simulate vein wrapping.

PMID- 24875031
TI  - What's new in foot and ankle surgery.

PMID- 24875032
TI  - The relative efficacy of antifibrinolytics in adolescent idiopathic scoliosis: a
      prospective randomized trial.
AB  - BACKGROUND: Antifibrinolytics can reduce intraoperative blood loss. The primary
      aim of this study was to determine the efficacy of intraoperative tranexamic
      acid, epsilon-aminocaproic acid, and placebo at reducing perioperative blood loss
      and the transfusion rate in patients with adolescent idiopathic scoliosis
      undergoing posterior spinal arthrodesis. METHODS: This is a prospective,
      randomized, double-blind comparison of tranexamic acid, epsilon-aminocaproic
      acid, and placebo used intraoperatively in patients with adolescent idiopathic
      scoliosis. One hundred and twenty-five patients with adolescent idiopathic
      scoliosis were randomly assigned to the tranexamic acid, epsilon-aminocaproic
      acid, or control groups. Parameters recorded included estimated blood loss,
      hematocrit, blood product usage, drain output, and total blood losses. The
      primary outcomes were intraoperative blood loss and postoperative drainage.
      Secondary outcomes were transfusion requirements and hematocrit changes both
      intraoperatively and postoperatively. RESULTS: One hundred and twenty-five
      patients (ninety-seven female and twenty-eight male, with a mean age of fifteen
      years) were randomized to receive tranexamic acid (thirty-six patients), epsilon
      aminocaproic acid (forty-two patients), or saline solution (forty-seven
      patients). The groups were similar at baseline, with one exception: the saline
      solution group had a higher estimated blood volume at baseline than the
      tranexamic acid group. Both tranexamic acid and epsilon-aminocaproic acid reduced
      the estimated blood loss per degree and estimated blood loss per pedicle screw.
      Epsilon-aminocaproic acid, but not tranexamic acid, reduced estimated blood loss
      and estimated blood loss per level. Tranexamic acid also reduced total blood
      losses compared with epsilon-aminocaproic acid or saline solution. In an analysis
      controlling for level, degree, and number of anchors, tranexamic acid reduced
      drain output and total blood losses. Tranexamic acid or epsilon-aminocaproic acid
      had a smaller decrease in hematocrit postoperatively. In an analysis controlling
      for the mean arterial pressure during surgical exposure, tranexamic acid reduced
      estimated blood loss and total blood losses. Overall, antifibrinolytics
      (tranexamic acid or epsilon-aminocaproic acid) reduced estimated blood loss,
      total blood losses, and the decline in hematocrit postoperatively compared with
      saline solution. There was no difference among the groups with respect to the
      transfusion rate, duration of surgery, levels fused, or pedicle screws placed.
      CONCLUSIONS: Tranexamic acid and epsilon-aminocaproic acid reduced operative
      blood loss but not transfusion rate. Tranexamic acid is more effective at
      reducing postoperative drainage and total blood losses compared with epsilon
      aminocaproic acid. Maintenance of the mean arterial pressure at <75 mm Hg during
      surgical exposure appears to be critical for maximizing antifibrinolytic benefit.
      LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a
      complete description of levels of evidence.

PMID- 24875033
TI  - Bicruciate substituting design does not improve maximal flexion in total knee
      arthroplasty: a randomized controlled trial.
AB  - BACKGROUND: An important factor in the functional results after total knee
      arthroplasty is the achieved maximal flexion. The main purpose of this study was
      to compare the maximal knee flexion one year after surgery in patients who
      received either the bicruciate substituting knee system or the conventional
      posterior stabilized system. METHODS: In a prospective randomized controlled
      trial, 124 patients presenting with osteoarthritis received the bicruciate
      substituting or the conventional posterior stabilized prosthesis. The primary
      outcome was the maximum flexion angle at one year postoperatively on a lateral
      radiograph made with the supine patient using manual force to bend the knee.
      Secondary outcomes were active flexion (lying and standing), the Knee Society
      Score, the Patella Scoring System score, the University of California Los Angeles
      score, the number and type of adverse device effects, and visual analog scale
      satisfaction up to two years postoperatively. The outcome measures of both groups
      were compared using one-sided t tests and non-parametric alternatives, with a
      significance level of p < 0.05. RESULTS: No significant differences between the
      two groups were observed in maximal flexion on radiographs and in active flexion
      at baseline. The median maximal flexion on radiographs was 127 degrees  (range,
      83 degrees  to 150 degrees ) for the bicruciate substituting group and 125
      degrees  (range, 74 degrees  to 145 degrees ) for the conventional posterior
      stabilized group. The two groups showed comparable two-year results with respect
      to the Knee Society Score, the Patella Scoring System, the University of
      California Los Angeles score, and visual analog scale satisfaction. In the
      bicruciate substituting group, forty-one adverse device effects in twenty-six
      patients were reported, including three total system revisions and fourteen
      manipulations under anesthesia, compared with the conventional posterior
      stabilized group, in which sixteen adverse device effects were observed in
      thirteen patients, including six manipulations under anesthesia (p = 0.012).
      CONCLUSIONS: Patients who receive a bicruciate substituting system compared with
      those who receive a conventional posterior stabilized system have comparable knee
      flexion characteristics and clinical and functional outcomes but more
      complications by two years after total knee arthroplasty. LEVEL OF EVIDENCE:
      Therapeutic Level I. See Instructions for Authors for a complete description of
      levels of evidence.

PMID- 24875034
TI  - Radiographic changes in patients with pseudarthrosis after posterior lumbar
      interbody arthrodesis using carbon interbody cages: a prospective five-year
      study.
AB  - BACKGROUND: The aim of this study was to demonstrate longitudinal radiographic
      changes at up to five years in patients with pseudarthrosis after posterior
      lumbar interbody arthrodesis using carbon interbody cages. METHODS: From 2003 to
      2006, prospective longitudinal radiographic and CT (computed tomography) scan
      evaluations were made at up to five years after posterior lumbar interbody
      arthrodesis using carbon interbody cages at one or two levels in 153 consecutive
      patients. At the one-year evaluation, seventeen patients with early
      pseudarthrosis at nineteen levels were selected as subjects on the basis of one
      or more of the following characteristics: complete absence of osseous bridging
      between the upper and lower vertebrae, angular motion of >=5 degrees , and/or
      radiolucent zones surrounding the implant. Angular motion, continuity of osseous
      bridging, grafted bone quantity, and radiolucent zones around the pedicle screws
      and cages were observed annually until five years. RESULTS: The mean angular
      motion of five levels that exhibited >=5 degrees  of motion at one year began to
      decrease significantly thereafter (p = 0.046), and no level showed movement of
      >=5 degrees  at five years. The mean grade of the radiolucent zones around the
      screws on CT showed significant improvements at two years (p = 0.039) and three
      years (p < 0.01). The radiolucent zones around the screws disappeared at twelve
      of sixteen levels by five years, and the radiolucent zones around the cages
      disappeared in eleven of seventeen levels by five years. Of eighteen levels with
      early pseudarthrosis, seven (39%) were assessed as successfully fused at three
      years and twelve (67%) at five years. Four (80%) of five patients with a
      radiolucent zone of >1 mm around the entire cage on CT at one year showed
      continuing pseudarthrosis at five years, whereas only two (15%) of thirteen
      patients without this finding did (crude relative risk = 5.2; 95% confidence
      interval, 1.35 to 20.02). A radiolucent zone of >1 mm around the entire cage on
      CT at one year could be an early predictor of permanent pseudarthrosis (odds
      ratio = 123; 95% confidence interval, 1.03 to 14,680). CONCLUSIONS: The interbody
      arthrodesis site in patients with early pseudarthrosis may begin to change to a
      successful fusion one or two years after surgery, with two-thirds of such
      patients exhibiting successful fusion five years after surgery. Final assessment
      of pseudarthrosis should be performed at least three years after surgery. A
      radiolucent zone of >1 mm around the entire interbody cage on CT at one year may
      require early additional surgery. LEVEL OF EVIDENCE: Therapeutic Level IV. See
      Instructions for Authors for a complete description of levels of evidence.

PMID- 24875035
TI  - Symptomatic venous thromboembolism uncommon without thromboprophylaxis after
      isolated lower-limb fracture: the knee-to-ankle fracture (KAF) cohort study.
AB  - BACKGROUND: The prevalence of deep vein thrombosis as demonstrated by routine
      venography in patients with distal lower-extremity injury requiring cast
      immobilization or surgery is 10% to 40%. These deep vein thromboses are usually
      asymptomatic and distal, and the need for thromboprophylaxis in these patients is
      not known. METHODS: We conducted a multicenter prospective cohort study to define
      the prevalence of symptomatic venous thromboembolism in patients with a tibial,
      fibular, or ankle fracture (treated nonoperatively) or a patellar or foot
      fracture (treated operatively or conservatively). Consecutive patients were
      enrolled at five Ontario, Canada, hospitals within ninety-six hours after injury,
      and they were followed with a telephone interview at two, six, and twelve weeks.
      Thromboprophylaxis was not allowed. Suspected venous thromboembolism was
      investigated in a standardized manner. RESULTS: From August 2002 to June 2005,
      1200 patients were enrolled, and a three-month follow-up was completed for 98% of
      them. Eighty-two percent of the patients were treated with cast or splint
      immobilization for an average (and standard deviation) of 42 +/- 32 days.
      Overall, seven patients (0.6%; 95% confidence interval [CI] = 0.2% to 1.2%) had
      symptomatic, objectively confirmed venous thromboembolism. Two of them had
      proximal deep vein thrombosis; three, calf deep vein thrombosis; and two,
      pulmonary embolism. There were no fatal pulmonary emboli. CONCLUSIONS:
      Symptomatic venous thromboembolism is an infrequent complication after fractures
      of the distal part of the lower limb requiring cast immobilization and managed
      without thromboprophylaxis. Given these estimates of symptomatic venous
      thromboembolism, the risk-benefit ratio and cost-effectiveness of routine
      anticoagulant prophylaxis are unlikely to be favorable for these patients. LEVEL
      OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete
      description of levels of evidence.

PMID- 24875036
TI  - Telementoring: use of augmented reality in orthopaedic education: AAOS exhibit
      selection.
AB  - BACKGROUND: Virtual interactive presence (VIP) is a new technology that allows an
      individual to deliver real-time virtual assistance to another geographically
      remote individual via a standard Internet connection. The objectives of this
      pilot study were to evaluate the efficiency and performance of a VIP system
      implemented in an operating room setting, determine the potential utility of the
      system for guidance of surgical procedures, and assess the safety of the system.
      METHODS: Following institutional review board approval, fifteen patients
      underwent arthroscopic shoulder procedures. Two VIP stations were used, one in
      the operating room and the other in an adjoining dictation room. The attending
      surgeon proctored operating resident surgeons from the dictation room until his
      physical presence was required in the operating room. Following each procedure,
      the attending surgeon, resident surgeons, and three surgical staff members
      completed a Likert-scale questionnaire regarding the educational utility,
      efficiency of use, and safety of the system. The operative time was also compared
      with historical data. RESULTS: Both attending and resident surgeons assigned a
      favorable rating to the utility of the VIP to highlight anatomy and provide
      feedback to the resident (p > 0.05 for the difference). Both groups agreed that
      the system was easy to use and that safety was not compromised (p > 0.05). The
      majority of resident and attending surgeon responses indicated no perceptible lag
      between motions (95% and 100%, respectively; p > 0.99) and no interference of the
      VIP system with the surgical procedure (85% and 100%, respectively; p = 0.24).
      The mean operative times with and without VIP use did not differ significantly
      for rotator cuff repair (p = 0.90) or for treatment of instability (p = 0.57).
      CONCLUSIONS: This pilot study revealed that the VIP technology was efficient,
      safe, and effective as a teaching tool. The attending and resident surgeons
      agreed that training was enhanced, and this occurred without increasing operative
      times. Furthermore, the attending surgeon believed that this technology improved
      teaching effectiveness. These results are promising, and further objective
      quantification is warranted.

PMID- 24875037
TI  - Public perception regarding anterior cruciate ligament reconstruction.
AB  - BACKGROUND: Relatively little information exists regarding the public's
      perception of anterior cruciate ligament (ACL) injuries and their treatment. The
      objective of this study was to test the hypothesis that the public's
      understanding of ACL surgery may be incorrect with regard to various aspects of
      this procedure and to identify issues to emphasize in patient education. METHODS:
      This study utilized a forty-three-question survey designed to measure an
      individual's knowledge base and perception of ACL reconstruction with regard to
      the anatomy, function, indications, operative technique, risks, recovery time,
      and overall benefits of the procedure. Eligible individuals were between fifteen
      and sixty years of age. Study participants were recruited from an academic
      orthopaedic sports medicine clinic, a collegiate athletic training room, and
      various public venues. RESULTS: A total of 210 individuals (106 men and 104
      women) with a mean age of thirty were surveyed. Educational level of the
      respondents varied widely. Twenty-seven percent of the respondents were employed
      in a health-care setting. Sixty-five percent of the respondents rated their ACL
      knowledge level as "little" or "none." Participants' self-perception of ACL
      knowledge was highly correlated with their survey scores on questions with a
      specific correct answer (p < 0.001). Almost one-third thought that surgical
      treatment involved repair of the torn ligament rather than reconstruction. Over
      half (56%) of the respondents preferred an autograft for ligament reconstruction,
      compared with 4% who preferred an allograft. The ability to return to sports
      after ACL surgery was the most important concern, followed by the risk of
      developing osteoarthritis. CONCLUSIONS: There is wide variability in the lay
      public's knowledge level of ACL injuries; a substantial number of misguided
      perceptions were identified. Return to sports and risk for future osteoarthritis
      following ACL surgery appear to be the most important factors to the lay public.
      Focusing educational efforts on areas of knowledge deficits may be particularly
      important for patients of physicians who treat ACL injuries.

PMID- 24875038
TI  - Shoulder pain does not parallel rotator cuff tear size-what does that tell us?:
      Commentary on an article by Warren R. Dunn, MD, MPH, et al.: "symptoms of pain do
      not correlate with rotator cuff tear severity. A cross-sectional study of 393
      patients with a symptomatic atraumatic full-thickness rotator cuff tear".

PMID- 24875039
TI  - Patients who have undergone non-arthroplasty operative procedures are at higher
      risk to require total knee arthroplasty: commentary on the article by Robert H.
      Brophy, MD, et al.: "total knee arthroplasty after previous knee surgery:
      expected interval and the effect on patient age".

PMID- 24875040
TI  - Hardly depressing and far from painful: commentary on an article by Daniel A.
      London, BA, et al.: "the impact of depression and pain catastrophization on
      initial presentation and treatment outcomes for atraumatic hand conditions".

PMID- 24875041
TI  - Determinants of countermovement jump performance: a kinetic and kinematic
      analysis.
AB  - This study aimed to investigate the contributions of kinetic and kinematic
      parameters to inter-individual variation in countermovement jump (CMJ)
      performance. Two-dimensional kinematic data and ground reaction forces during a
      CMJ were recorded for 18 males of varying jumping experience. Ten kinetic and
      eight kinematic parameters were determined for each performance, describing peak
      lower-limb joint torques and powers, concentric knee extension rate of torque
      development and CMJ technique. Participants also completed a series of isometric
      knee extensions to measure the rate of torque development and peak torque. CMJ
      height ranged from 0.38 to 0.73 m (mean 0.55 +/- 0.09 m). CMJ peak knee power,
      peak ankle power and take-off shoulder angle explained 74% of this observed
      variation. CMJ kinematic (58%) and CMJ kinetic (57%) parameters explained a much
      larger proportion of the jump height variation than the isometric parameters
      (18%), suggesting that coachable technique factors and the joint kinetics during
      the jump are important determinants of CMJ performance. Technique, specifically
      greater ankle plantar-flexion and shoulder flexion at take-off (together
      explaining 58% of the CMJ height variation), likely influences the extent to
      which maximal muscle capabilities can be utilised during the jump.

PMID- 24875043
TI  - Longitudinal associations between maternal disrupted representations, maternal
      interactive behavior and infant attachment: a comparison between full-term and
      preterm dyads.
AB  - This prospective study examined whether or not a mother's representations of her
      infant were more often disrupted after premature childbirth. Furthermore, the
      study examined if different components of maternal interactive behavior mediated
      the relation between maternal disrupted representations and infant attachment.
      The participants were mothers of full-term (n = 75), moderately preterm (n = 68)
      and very preterm infants (n = 67). Maternal representations were assessed by the
      Working Model of the Child Interview at 6 months post-partum. Maternal
      interactive behavior was evaluated at 6 and 24 months post-partum, using the
      National Institute of Child Health and Human Development Early Care Research
      Network mother-infant observation scales. Infant attachment was observed at 24
      months post-partum and was coded by the Attachment Q-Set. The results reveal that
      a premature childbirth does not necessarily generate disrupted maternal
      representations of the infant. Furthermore, maternal interactive behavior appears
      to be an important mechanism through which maternal representations influence the
      development of infant attachment in full-term and preterm infants. Early
      assessment of maternal representations can identify mother-infant dyads at risk,
      in full-term and preterm samples. 

PMID- 24875044
TI  - Effects of different swimming race constraints on turning movements.
AB  - The aim of this study was to investigate the effects of different swimming race
      constraints on the evolution of turn parameters. One hundred and fifty-eight
      national and regional level 200-m (meters) male swimming performances were video
      analyzed using the individualized-distance model in the Open Comunidad de Madrid
      tournament. Turn (p<.001, ES=0.36) and underwater distances (p<.001, ES=0.38) as
      well as turn velocity (p<.001, ES=0.69) significantly dropped throughout the
      race, although stroke velocity and underwater velocity were maintained in the
      last lap of the race (p>.05). Higher expertise swimmers obtained faster average
      velocities and longer distances in all the turn phases (p<.001, ES=0.59), except
      the approach distance. In addition, national level swimmers showed the ability to
      maintain most of the turn parameters throughout the race, which assisted them in
      improving average velocity at the end of races. Therefore, the variations in the
      turning movements of a swimming race were expertise-related and focused on
      optimizing average velocity. Turning skills should be included in the swimming
      race action plan. 

PMID- 24875042
TI  - A viral over-expression system for the major malaria mosquito Anopheles gambiae.
AB  - Understanding pathogen/mosquito interactions is essential for developing novel
      strategies to control mosquito-borne diseases. Technical advances in reverse
      genetics, such as RNA interference (RNAi), have facilitated elucidation of
      components of the mosquito immune system that are antagonistic to pathogen
      development, and host proteins essential for parasite development. Forward
      genetic approaches, however, are limited to generation of transgenic insects, and
      while powerful, mosquito transgenesis is a resource- and time-intensive technique
      that is not broadly available to most laboratories. The ability to easily "over
      express" genes would enhance molecular studies in vector biology and expedite
      elucidation of pathogen-refractory genes without the need to make transgenic
      insects. We developed and characterized an efficient Anopheles gambiae densovirus
      (AgDNV) over-expression system for the major malaria vector Anopheles gambiae.
      High-levels of gene expression were detected at 3 days post-infection and
      increased over time, suggesting this is an effective system for gene induction.
      Strong expression was observed in the fat body and ovaries. We validated multiple
      short promoters for gene induction studies. Finally, we developed a polycistronic
      system to simultaneously express multiple genes of interest. This AgDNV-based
      toolset allows for consistent transduction of genes of interest and will be a
      powerful molecular tool for research in Anopheles gambiae mosquitoes. 

PMID- 24875045
TI  - Jump performance and augmented feedback: immediate benefits and long-term
      training effects.
AB  - Drop jumps and their adaptations to training have been extensively investigated.
      However, the influence of augmented feedback (aF) on stretch-shortening cycle
      (SSC) was not scrutinized so far despite the well-known positive effects of aF on
      motor performance and motor learning. The aim of the present study was therefore
      to investigate the effects of aF by evaluating immediate within-session effects
      and long-term adaptations. 34 participants were assigned to three groups that
      trained drop jumps with different relative frequencies of aF about their jump
      height: 100%, 50%, or 0%. A significant within-session effect of aF on jump
      height was observed before and also after the training period (pre: +4.6%; post:
      +2.6%). In the long-term (comparing pre- to post-measurement), the 100% group
      showed the greatest increase in jump height (+14%), followed by the 50% (+10%)
      and the 0% group (+6%). The importance of aF on drop jumps is therefore twofold:
      (i) to immediately increase jump performance and (ii) to improve long-term
      training efficacy. In contrast to the proposition of the guidance hypothesis,
      high frequency of aF seems to be beneficial when maximizing SSC-performance. As
      jump height cannot be quantified without objective technical measures it is
      recommended to include them into daily training. 

PMID- 24875046
TI  - Acetal-initiated Prins bicyclization for the synthesis of hexahydrofuro-[3,4
      c]furan lignans and octahydropyrano[3,4-c]pyran derivatives.
AB  - An acetal-initiated Prins bicyclization approach has been developed for the
      stereoselective synthesis of hexahydrofuro[3,4-c]furan lignans. This also
      provides a direct way to generate a new series of octahydropyrano[3,4-c]pyran
      derivatives in a single-step process. 

PMID- 24875048
TI  - Epigenetic approaches for bipolar disorder drug discovery.
AB  - INTRODUCTION: Bipolar disorder (BD) is a common psychiatric disorder which can be
      devastating to affected patients, if not adequately treated. Although effective
      drugs are presently available for treating BD, many patients do not respond
      adequately. There are also problems with the current management of patients with
      this disorder: drug-resistant BD, rapid-cycling BD and cognitive decline in BD
      patients despite drug therapy. In this context, new and more effective drugs will
      be valuable in the clinical management of BD patients. AREAS COVERED: This
      article discusses the potential of the use of epigenetic drugs in the management
      of BD. Although several classes of epigenetic drugs are under investigation, at
      present, most attention is focused on two classes of epigenetic drugs: DNA
      methyltransferase inhibitors and histone deacetylase inhibitors (HDACis). Several
      preclinical drug trials of HDACis for the treatment of BD have been conducted.
      EXPERT OPINION: HDACis have shown promising results in preclinical studies of BD.
      However, the currently available HDACis suffer from acting non-specifically on
      HDAC isozymes. More isozyme-specific HDACis are likely to have greater efficacy
      and less toxicity than the current HDACis. It is suggested that efforts should be
      made to develop such HDACis. Once such HDACis with adequate ability to cross the
      blood-brain barrier become available, investigators could consider proceeding to
      clinical trials of HDACis for the treatment of BD.

PMID- 24875047
TI  - Cross-country variation in the sociodemographic factors associated with major
      depressive episode in Norway, the United Kingdom, Ghana, and Kenya.
AB  - Studies based on Western samples generally show that status characteristics like
      gender or marital status are associated with better mental health for individuals
      who occupy advantageous positions, such as men or the married. However, these
      patterns may not hold in developing regions that differ in important ways from
      the West. Guided by the Stress Process Model (SPM), this study uses logistic
      regression to examine the effect of gender, education, and other status
      characteristics on major depressive episode (MDE). Similarities and differences
      in these associations across two Western and two African countries are also
      assessed. Nationally representative data for adults ages 18 years and older are
      from the World Health Surveys (2002-2004) for Norway (N = 943), the United
      Kingdom (UK: N = 1195), Ghana (N = 3922), and Kenya (N = 4331). Results indicate
      a mixed pattern of associations between status characteristics and MDE across the
      four countries. Norwegian men face higher risk of MDE than Norwegian women-an
      anomalous finding. With some exceptions, education and employment status are not
      significantly related to MDE across the countries, providing little support for
      SPM. Marital status differences in risk of MDE are largest for Norway and
      smallest for Ghana. For the UK, men face lower risk of MDE than women across
      levels of mastery, and the gender gap in MDE is larger at higher levels of
      mastery. Overall, there is some heterogeneity in the associations between status
      characteristics and MDE even in somewhat similar environments like Ghana and
      Kenya. This study extends the reach of SPM to settings in sub-Saharan Africa, and
      contributes to the sparse empirical literature on the prevalence and
      sociodemographic correlates of MDE in the general populations of Ghana and Kenya.

PMID- 24875050
TI  - Release behaviour of single pellets and internal fine 3D structural features co
      define the in vitro drug release profile.
AB  - Multi-pellet formulations are advantageous for the controlled release of drugs
      over single-unit dosage forms. To understand the diffusion controlled drug
      release mechanism, the pellet structure and drug release from a single pellet
      (not at dose level) were studied using synchrotron radiation X-ray computed
      microtomography (SR-MUCT) and a sensitive LC/MS/MS method. The purpose of this
      article is to introduce a powerful, non-invasive and quantitative technique for
      studying individual pellet microstructures and to investigate the relationship
      between the microstructure and drug release from single pellets. The data from
      the single pellet dissolution measurements demonstrated that the release profile
      of capsules containing approximately 1,000 pellets per unit dose was the
      summation of the release profiles of the individual pellets. The release profiles
      of single tamsulosin hydrochloride (TSH) pellets formed three groups when a
      cluster analysis was performed, and the dissolution rate of the individual
      pellets correlated well with the combined effects of the drug loading, volume and
      surface area of the pellets (R(2) = 0.9429). In addition, the void
      microstructures within the pellet were critical during drug release. Therefore,
      SR-MUCT is a powerful tool for quantitatively elucidating the three-dimensional
      microstructure of the individual pellets; because the microstructure controls
      drug release, it is an important parameter in the quality control of multi-pellet
      formulations.

PMID- 24875051
TI  - The gender of cell lines matters when screening for novel anti-cancer drugs.
AB  - Current reports indicated that the gender origin of cells is important in all
      facets of experimental biology. To explore this matter using an anticancer high
      throughput screening platform, seven male- and seven female-derived human cell
      lines, six from cancer patients in each group, were exposed to 81 novel
      cytotoxins. In this screen, the findings revealed that 79 out of 81 of the
      compounds consistently inflicted higher levels of toxicity towards male derived
      cells, emphasizing that there is indeed a gender-related difference in cell
      sensitivity to these anti-neoplastic agents. This gender-related drug sensitivity
      and toxicity explored at the molecular and cellular level emerged from a drug
      discovery enterprise. 

PMID- 24875049
TI  - Ras-mediated deregulation of the circadian clock in cancer.
AB  - Circadian rhythms are essential to the temporal regulation of molecular processes
      in living systems and as such to life itself. Deregulation of these rhythms leads
      to failures in biological processes and eventually to the manifestation of
      pathological phenotypes including cancer. To address the questions as to what are
      the elicitors of a disrupted clock in cancer, we applied a systems biology
      approach to correlate experimental, bioinformatics and modelling data from
      several cell line models for colorectal and skin cancer. We found strong and weak
      circadian oscillators within the same type of cancer and identified a set of
      genes, which allows the discrimination between the two oscillator-types. Among
      those genes are IFNGR2, PITX2, RFWD2, PPARgamma, LOXL2, Rab6 and SPARC, all
      involved in cancer-related pathways. Using a bioinformatics approach, we extended
      the core-clock network and present its interconnection to the discriminative set
      of genes. Interestingly, such gene signatures link the clock to oncogenic
      pathways like the RAS/MAPK pathway. To investigate the potential impact of the
      RAS/MAPK pathway - a major driver of colorectal carcinogenesis - on the circadian
      clock, we used a computational model which predicted that perturbation of BMAL1
      mediated transcription can generate the circadian phenotypes similar to those
      observed in metastatic cell lines. Using an inducible RAS expression system, we
      show that overexpression of RAS disrupts the circadian clock and leads to an
      increase of the circadian period while RAS inhibition causes a shortening of
      period length, as predicted by our mathematical simulations. Together, our data
      demonstrate that perturbations induced by a single oncogene are sufficient to
      deregulate the mammalian circadian clock.

PMID- 24875052
TI  - Solid lipid particles for oral delivery of peptide and protein drugs III - the
      effect of fed state conditions on the in vitro release and degradation of
      desmopressin.
AB  - The effect of food intake on the release and degradation of peptide drugs from
      solid lipid particles is unknown and was therefore investigated in vitro using
      different fed state media in a lipolysis model. Desmopressin was used as a model
      peptide and incorporated into solid lipid particles consisting of trimyristin
      (TG14), tripalmitin (TG16), and tristearin (TG18), respectively. Fasted state and
      fed state media with varying phospholipid and bile salt concentrations, as well
      as fed state media with milk and oleic acid glycerides, respectively, were used
      as the release media. The presence of oleic acid glycerides accelerated the
      release of desmopressin significantly from all solid lipid particles both in the
      presence and absence of lipase. The presence of oleic acid glycerides also
      reduced the degradation rate of desmopressin, probably due to the interactions
      between the lipids and the protease or desmopressin. Addition of a medium chain
      triglyceride, trilaurin, in combination with drug-loaded lipid particles
      diminished the food effect on the TG18 particles, and trilaurin is therefore
      proposed to be a suitable excipient for reduction of the food effect. Overall,
      the present study shows that strategies to reduce food effect, such as adding
      trilaurin, for lipid particle formulations should be considered as drug release
      from such formulations might be influenced by the presence of food in the
      gastrointestinal tract.

PMID- 24875054
TI  - F-spondin deficient mice have a high bone mass phenotype.
AB  - F-spondin is a pericellular matrix protein upregulated in developing growth plate
      cartilage and articular cartilage during osteoarthritis. To address its function
      in bone and cartilage in vivo, we generated mice that were deficient for the F
      spondin gene, Spon1. Spon1-/- mice were viable and developed normally to
      adulthood with no major skeletal abnormalities. At 6 months, femurs and tibiae of
      Spon1-/- mice exhibited increased bone mass, evidenced by histological staining
      and micro CT analyses, which persisted up to 12 months. In contrast, no major
      abnormalities were observed in articular cartilage at any age group.
      Immunohistochemical staining of femurs and tibiae revealed increased levels of
      periostin, alkaline phosphate and tartrate resistant acid phosphatase (TRAP)
      activity in the growth plate region of Spon1-/- mice, suggesting elevated bone
      synthesis and turnover. However, there were no differences in serum levels of
      TRAP, the bone resorption marker, CTX-1, or osteoclast differentiation potential
      between genotypes. Knockout mice also exhibited reduced levels of TGF-beta1 in
      serum and cultured costal chondrocytes relative to wild type. This was
      accompanied by increased levels of the BMP-regulatory SMADs, P-SMAD1/5 in tibiae
      and chondrocytes. Our findings indicate a previously unrecognized role for Spon1
      as a negative regulator of bone mass. We speculate that Spon1 deletion leads to a
      local and systemic reduction of TGF-beta levels resulting in increased BMP
      signaling and increased bone deposition in adult mice. 

PMID- 24875055
TI  - A novel universal neutralizing monoclonal antibody against enterovirus 71 that
      targets the highly conserved "knob" region of VP3 protein.
AB  - Hand, foot and mouth disease caused by enterovirus 71(EV71) leads to the majority
      of neurological complications and death in young children. While putative
      inactivated vaccines are only now undergoing clinical trials, no specific
      treatment options exist yet. Ideally, EV71 specific intravenous immunoglobulins
      could be developed for targeted treatment of severe cases. To date, only a single
      universally neutralizing monoclonal antibody against a conserved linear epitope
      of VP1 has been identified. Other enteroviruses have been shown to possess major
      conformational neutralizing epitopes on both the VP2 and VP3 capsid proteins.
      Hence, we attempted to isolate such neutralizing antibodies against
      conformational epitopes for their potential in the treatment of infection as well
      as differential diagnosis and vaccine optimization. Here we describe a universal
      neutralizing monoclonal antibody that recognizes a conserved conformational
      epitope of EV71 which was mapped using escape mutants. Eight escape mutants from
      different subgenogroups (A, B2, B4, C2, C4) were rescued; they harbored three
      essential mutations either at amino acid positions 59, 62 or 67 of the VP3
      protein which are all situated in the "knob" region. The escape mutant phenotype
      could be mimicked by incorporating these mutations into reverse genetically
      engineered viruses showing that P59L, A62D, A62P and E67D abolish both monoclonal
      antibody binding and neutralization activity. This is the first conformational
      neutralization epitope mapped on VP3 for EV71. 

PMID- 24875057
TI  - Prevalence and clinical significance of occult fractures in children with
      radiograph-negative acute ankle injury. A meta-analysis.
AB  - BACKGROUND AND PURPOSE: Plain radiographs may fail to reveal an ankle fracture in
      children because of developmental and anatomical characteristics. In this
      systematic review and meta- analysis, we estimated the prevalence of occult
      fractures in children with acute ankle injuries and clinical suspicion of
      fracture, and assessed the diagnostic accuracy of ultrasound (US) in the
      detection of occult fractures. METHODS: We searched the literature and included
      studies reporting the prevalence of occult fractures in children with acute ankle
      injuries and clinical suspicion of fracture. Proportion meta-analysis was
      performed to calculate the pooled prevalence of occult fractures. For each
      individual study exploring the US diagnostic accuracy, we calculated US operating
      characteristics. RESULTS: 9 studies (involving 187 patients) using magnetic
      resonance imaging (MRI) (n = 5) or late radiographs (n = 4) as reference standard
      were included, 2 of which also assessed the diagnostic accuracy of US. Out of the
      187 children, 41 were found to have an occult fracture. The pooled prevalence of
      occult fractures was 24% (95% CI: 18-31). The operating characteristics for
      detection of occult ankle fractures by US ranged in positive likelihood ratio
      (LR) from 9 to 20, and in negative LR from 0.04 to 0.08. INTERPRETATION: A
      substantial proportion of fractures may be overlooked on plain radiographs in
      children with acute ankle injuries and clinical suspicion of fracture. US appears
      to be a promising method for detection of ankle fractures in such children when
      plain radiographs are negative.

PMID- 24875058
TI  - 10-year results of the uncemented Allofit press-fit cup in young patients.
AB  - BACKGROUND AND PURPOSE: Uncemented acetabular components in primary total hip
      arthroplasty (THA) are commonly used today, but few studies have evaluated their
      survival into the second decade in young and active patients. We report on a
      minimum 10-year follow-up of an uncemented press-fit acetabular component that is
      still in clinical use. METHODS: We examined the clinical and radiographic results
      of our first 121 consecutive cementless THAs using a cementless, grit-blasted,
      non-porous, titanium alloy press-fit cup (Allofit; Zimmer Inc., Warsaw, IN)
      without additional screw fixation in 116 patients. Mean age at surgery was 51 (21
      60) years. Mean time of follow-up evaluation was 11 (10-12) years. RESULTS: At
      final follow-up, 8 patients had died (8 hips), and 1 patient (1 hip) was lost to
      follow-up. 3 hips in 3 patients had undergone acetabular revision, 2 for deep
      infection and 1 for aseptic acetabular loosening. There were no impending
      revisions at the most recent follow-up. We did not detect periacetabular
      osteolysis or loosening on plain radiographs in those hips that were evaluated
      radiographically (n = 90; 83% of the hips available at a minimum of 10 years).
      Kaplan-Meier survival analysis using revision of the acetabular component for any
      reason (including isolated inlay revisions) as endpoint estimated the 11-year
      survival rate at 98% (95% CI: 92-99). INTERPRETATION: Uncemented acetabular
      fixation using the Allofit press-fit cup without additional screws was excellent
      into early in the second decade in this young and active patient cohort. The rate
      of complications related to the liner and to osteolysis was low.

PMID- 24875059
TI  - Microcephaly disease gene Wdr62 regulates mitotic progression of embryonic neural
      stem cells and brain size.
AB  - Human genetic studies have established a link between a class of centrosome
      proteins and microcephaly. Current studies of microcephaly focus on defective
      centrosome/spindle orientation. Mutations in WDR62 are associated with
      microcephaly and other cortical abnormalities in humans. Here we create a mouse
      model of Wdr62 deficiency and find that the mice exhibit reduced brain size due
      to decreased neural progenitor cells (NPCs). Wdr62 depleted cells show spindle
      instability, spindle assembly checkpoint (SAC) activation, mitotic arrest and
      cell death. Mechanistically, Wdr62 associates and genetically interacts with
      Aurora A to regulate spindle formation, mitotic progression and brain size. Our
      results suggest that Wdr62 interacts with Aurora A to control mitotic
      progression, and loss of these interactions leads to mitotic delay and cell death
      of NPCs, which could be a potential cause of human microcephaly. 

PMID- 24875060
TI  - Correlation between human and model observer performance for discrimination task
      in CT.
AB  - Although physical metrics can objectively characterize computed tomography (CT)
      image quality, quantitative approaches to predict human observer performance are
      more accurate and clinically relevant. This study compared a modified channelized
      Hotelling model observer (CHO) with human observers in a shape discrimination
      task. Eight lesion-mimicking rods (two contrasts, two sizes and two shapes) were
      inserted into a 35 * 26 cm(2) torso-shaped water phantom and scanned 100 times on
      a 128-slice CT scanner at five dose levels. CT images were reconstructed using
      filtered backprojection (FBP) and iterative reconstruction (IR) techniques. Two
      alternative forced choice studies were constructed with hexagonal and circular
      rod images put side-by-side in a randomized order. An edge mask was introduced to
      CHO to reflect the human observers' emphasis on lesion boundaries in
      discriminating shape. For small size lesions, the performance of three human
      observers and the modified CHO was highly correlated across lesion contrasts, CT
      doses and reconstruction algorithms; while for large size lesions, a ceiling
      effect was observed for both human and model observers' performance at high
      doses. Our result suggests the potential of CHO to predict human observer
      performance for both FBP and IR. For this shape discrimination task with uniform
      background, IR significantly improved human and model observer performance
      compared to FBP, with the amount of improvement depending on lesion size,
      contrast and dose. 

PMID- 24875061
TI  - Bovine tuberculosis: within-herd transmission models to support and direct the
      decision-making process.
AB  - Use of mathematical models to study the transmission dynamics of infectious
      diseases is becoming increasingly common in veterinary sciences. However,
      modeling chronic infectious diseases such as bovine tuberculosis (bTB) is
      particularly challenging due to the substantial uncertainty associated with the
      epidemiology of the disease. Here, the methodological approaches used to model
      bTB and published in the peer-reviewed literature in the last decades were
      reviewed with a focus on the impact that the models' assumptions may have had on
      their results, such as the assumption of density vs. frequency-dependent
      transmission, the existence of non-infectious and non-detectable stages, and the
      effect of extrinsic sources of infection (usually associated with wildlife
      reservoirs). Although all studies suggested a relatively low rate of within-herd
      transmission of bTB when test-and-cull programs are in place, differences in the
      estimated length of the infection stages, sensitivity and specificity of the
      tests used and probable type of transmission (density or frequency dependent)
      were observed. Additional improvements, such as exploring the usefulness of
      contact-networks instead of assuming homogeneous mixing of animals, may help to
      build better models that can help to design, evaluate and monitor control and
      eradication strategies against bTB.

PMID- 24875062
TI  - Influence of oral co-administration of a preparation containing calcium and
      magnesium and food on enrofloxacin pharmacokinetics.
AB  - The objective of this study has been to determine the influence of food and ions
      on the pharmacokinetics of enrofloxacin (ENRO) in turkeys, administered per os at
      a dose of 10 mg/kg of body weight (b.w.). Co-administration of ENRO with ions or
      with food significantly retarded its absorption, and the interaction was more
      pronounced when the drug was given together with food. The bioavailability of
      ENRO was 65.78 +/- 7.81% and 47.99 +/- 9.48% with ions and food, respectively.
      The maximum concentration (Cmax) in plasma of animals exposed to ions reached
      0.87 +/- 0.26 MUg/ml in a tmax of 2.07 +/- 0.76 h; in animals which were fed
      while medicated, the analogous parameters were 0.36 +/- 0.13 MUg/ml and 8.06 +/-
      3.08 h. The PK/PD analysis demonstrated that a decrease in the concentration of
      ENRO in turkeys' blood due to the interaction with ions or food might impair the
      drug's clinical efficacy toward some pathogenic microorganisms in turkeys if a
      routine dose of 10 mg ENRO/kg b.w. is administered. 

PMID- 24875063
TI  - Morbidity and mortality of invertebrates, amphibians, reptiles, and mammals at a
      major exotic companion animal wholesaler.
AB  - The authors formally investigated a major international wildlife wholesaler and
      subsequently confiscated more than 26,400 nonhuman animals of 171 species and
      types. Approximately 80% of the nonhuman animals were identified as grossly sick,
      injured, or dead, with the remaining in suspected suboptimal condition. Almost
      3,500 deceased or moribund animals (12% of stock), mostly reptiles, were being
      discarded on a weekly basis. Mortality during the 6-week "stock turnover" period
      was determined to be 72%. During a 10-day period after confiscation, mortality
      rates (including euthanasia for humane reasons) for the various taxa were 18% for
      invertebrates, 44.5% for amphibians, 41.6% for reptiles, and 5.5% for mammals.
      Causes of morbidity and mortality included cannibalism, crushing, dehydration,
      emaciation, hypothermic stress, infection, parasite infestation, starvation,
      overcrowding, stress/injuries, euthanasia on compassionate grounds, and
      undetermined causes. Contributing factors for disease and injury included poor
      hygiene; inadequate, unreliable, or inappropriate provision of food, water, heat,
      and humidity; presumed high levels of stress due to inappropriate housing leading
      to intraspecific aggression; absent or minimal environmental enrichment; and
      crowding. Risks for introduction of invasive species through escapes and/or
      spread of pathogens to naive populations also were identified. 

PMID- 24875064
TI  - Is the level of resistin appropriate for predicting atrial fibrillation?

PMID- 24875065
TI  - Left ventricular apical aneurysm and systolic dysfunction in hypertrophic
      cardiomyopathy.

PMID- 24875067
TI  - Orexin-a system neuromodulation by intrathecal baclofen.

PMID- 24875066
TI  - Pro re nata (as needed) psychotropic medication use in patients with borderline
      personality disorder and subjects with other personality disorders over 14 years
      of prospective follow-up.
AB  - The use of pro re nata (PRN; as needed) psychotropic medication in patients with
      borderline personality disorder (BPD) has not been well characterized. This study
      had 3 purposes, which are as follows: (1) to describe the prevalence of PRN
      psychotropic medication use among patients with BPD and comparison subjects with
      other personality disorders (OPD) over 14 years of prospective follow-up, (2) to
      examine the rates reported by patients with BPD who ever recovered and never
      recovered, and (3) to examine the reasons for taking PRN medication reported by
      these patients. Overall, the prevalence of PRN psychotropic medication use was
      initially approximately 3 times higher among patients with BPD than comparison
      subjects with OPD, with a significant one-third decline in the use of PRN
      medication reported by patients with BPD over time. In analyses restricted to
      patients with BPD, patients with BPD who never recovered were approximately twice
      as likely to use PRN medication than patients with BPD who ever recovered over
      time. In reasons for use, the rates of PRN medication use to decrease agitation
      for both diagnostic groups declined significantly over time, whereas they
      remained significantly higher among patients with BPD. Likewise, patients with
      BPD who never recovered reported higher use of PRN medication to decrease
      agitation than patients with BPD who ever recovered over time. The results of
      this study indicate that PRN psychotropic medication is widely used for the
      treatment of patients with BPD, particularly those who have not achieved a
      recovery in both the symptomatic and psychosocial realms. They also suggest that
      patients with BPD use proportionally more PRN medication to decrease agitation
      than comparison subjects with OPD, with lower proportional use to reduce
      agitation found among recovered patients with BPD. 

PMID- 24875068
TI  - Brief psychotic disorder after abrupt withdrawal of hydroxyzine hydrochloride.

PMID- 24875069
TI  - Serotonin-norepinephrine reuptake inhibitor-associated mixed episode in an
      adolescent with schizoaffective disorder.

PMID- 24875070
TI  - Comparing dopamine D(2) receptor occupancies for use in clinical practice:
      attractive proposition but fraught with pitfalls.

PMID- 24875071
TI  - Effect of methylphenidate on neurocognitive test battery: an evaluation according
      to the diagnostic and statistical manual of mental disorders, fourth edition,
      subtypes.
AB  - The aims of this study were to evaluate the neuropsychological characteristics of
      the restrictive (R) subtype according to the Diagnostic and Statistical Manual of
      Mental Disorders, Fourth Edition and the attention-deficit/hyperactivity disorder
      (ADHD) combined (CB) type and predominantly inattentive (PI) type subtypes and to
      evaluate whether methylphenidate (MPH) affects neurocognitive test battery scores
      according to these subtypes. This study included 360 children and adolescents
      (277 boys, 83 girls) between 7 and 15 years of age who had been diagnosed with
      ADHD and compared the neuropsychological characteristics and MPH treatment
      responses of patients with the R subtype-which has been suggested for inclusion
      among the ADHD subtypes in the Diagnostic and Statistical Manual of Mental
      Disorders, Fourth Edition-with those of patients with the PI and CB subtypes.
      They did not differ from the control subjects in the complex attention domain,
      which includes Continuous Performance Test, Stroop test, and Shifting Attention
      Test, which suggests that the R subtype displayed a lower level of deterioration
      in these domains compared with the PI and CB subtypes. The patients with the CB
      and PI subtypes did not differ from the control subjects in the Continuous
      Performance Test correct response domain, whereas those with the R subtype
      presented a poorer performance than the control subjects. The R subtype requires
      a more detailed evaluation because it presented similar results in the remaining
      neuropsychological evaluations and MPH responses. 

PMID- 24875072
TI  - Rapid resolution of suicidal behavior and depression with single low-dose
      ketamine intravenous push even after 6 months of follow-up.

PMID- 24875073
TI  - Antipsychotic doses among community-dwelling persons with Alzheimer disease in
      Finland.
AB  - Use of antipsychotics for treatment of behavioral and psychological symptoms of
      dementia is frequent among persons with Alzheimer disease (AD). Doses used in
      long-term therapy have not been previously reported. We describe antipsychotic
      doses used among community-dwelling persons with AD and investigate factors
      associated with high-dose use. The MEDALZ-2005 (Medication use and Alzheimer
      disease) cohort is a nationwide sample including all persons with clinically
      diagnosed AD at the end of year 2005 in Finland (n = 28,093). Data including
      prescriptions, comorbidities, and hospital discharge diagnoses were collected
      from nationwide registers. Antipsychotic doses in monotherapy were investigated
      during 2006 to 2009. Among 8920 antipsychotic users, 4% (n = 336) used
      antipsychotics with high dose. Typical antipsychotics were more often used with
      high dose than atypical antipsychotics. High-dose use was associated with younger
      age (<80 years) (odds ratio [OR], 1.71; 95% confidence interval [CI], 1.36
      2.15]), male sex (OR, 1.52; CI, 1.21-1.91), history of psychiatric disorder (OR,
      3.25; CI, 2.54-4.15), and inversely associated with Charlson Comorbidity Index
      score (score 1: OR, 0.74; CI, 0.57-0.97; score >=2: OR, 0.68; CI, 0.47-0.97). In
      conclusion, the majority of persons with AD used antipsychotics with low or
      medium dose. Typical antipsychotics were more often used with high dose than
      atypical antipsychotics, which indicates a need for precise dosing instructions
      in the treatment of behavioral and psychological symptoms of dementia. Clinicians
      should regularly assess dosing levels especially among men and those with history
      of psychiatric disorder. 

PMID- 24875074
TI  - Psychotic episode associated with sertraline and drug-related delirium: a case
      report.

PMID- 24875075
TI  - Reply to Dr Kawada: late-gestation selective serotonin reuptake inhibitor
      exposure and perinatal mortality.

PMID- 24875076
TI  - Low-dose imipramine for treatment of panic disorder during pregnancy: a
      retrospective chart review.
AB  - Although imipramine is one of the antidepressants that could be effective in the
      treatment of panic disorder, data on its usage for this diagnosis in the
      pregnancy period are limited. This report presents the results of 16 pregnant
      women with panic disorder without comorbid diagnosis who underwent low-dose
      imipramine (10-40 mg/d) treatment. According to the Clinical Global Impression
      Improvement Scale, 12 (75%) of 16 women responded to the treatment. The results
      suggest that low-dose imipramine may be useful for the treatment of panic
      disorder during pregnancy. 

PMID- 24875077
TI  - A double-blind, placebo-controlled trial of dextromethorphan combined with
      clonidine in the treatment of heroin withdrawal.
AB  - Dextromethorphan has been reported to ameliorate opioid withdrawal symptoms in
      both animal and human subjects. In the present study, we investigated the
      efficacy of dextromethorphan as an add-on medication in heroin detoxification
      treatment in a double-blind, placebo-controlled design. Sixty-five heroin
      dependent patients (male, 63; female, 2) participated in this inpatient
      detoxification trial after giving informed consent. Clonidine 0.075 mg 4 times a
      day was given as an antiwithdrawal medication at baseline. Each patient was then
      randomly assigned to treatment with either dextromethorphan 60 mg or placebo 4
      times a day as additional medication. Flurazepam 30 mg was given before bedtime
      for insomnia. Other medications that were allowed included loperamide for
      diarrhea and lorazepam for agitation. Participants were monitored using the
      Objective Opioid Withdrawal Scale 3 times a day as the primary outcome to compare
      drug efficacy between groups. Generalized estimating equation model analysis
      revealed that the Objective Opioid Withdrawal Scale had no group difference
      between dextromethorphan and placebo group overall (P = 0.29), whereas a
      significant difference between groups was found during day 3 to day 6 (P = 0.04)
      by post hoc analysis. There was no difference in the Clinical Global Impression
      Scale, patient's impression of treatment, and use of ancillary medications
      between groups. No severe adverse effects were noticed. We suggest that
      dextromethorphan has some beneficial effect in attenuating the severity of opioid
      withdrawal symptoms and can be used as an adjunction medication in the treatment
      of opioid withdrawal, whereas the exact efficacy needs further investigation.

PMID- 24875078
TI  - Correlation of haloperidol concentration in blood and cerebrospinal fluid: a
      pharmacokinetic study.

PMID- 24875079
TI  - Comments on Musha's theorem that an evanescent photon in the microtubule is a
      superluminal particle.
AB  - Takaaki Musha's research of high performance quantum computation in living
      systems is motivated by the theories of Penrose and Hameroff that microtubules in
      the brain function as quantum computers, and by those of Jibu and Yasue that the
      quantum states of microtubules depend upon boson condensates of evanescent
      photons. His work is based on the assumption that the evanescent photons
      described by Jibu et al. are superluminal and that they are tachyons defined and
      discussed by well-known physicists such as Sudarshan, Feinberg and Recami. Musha
      gives a brief justification for the assumption and sometimes calls it a theorem.
      However, the assumption is not valid because Jibu et al. stated that the
      evanescent photons have transmission speed smaller than that of light and that
      their mass is real and momentum is imaginary whereas a tachyon's mass is
      imaginary and momentum is real. We show here that Musha's proof of the "theorem"
      has errors and hence his theorem/assumption is not valid. This article is not
      meant to further discuss any biological aspects of the brain but only to comment
      on the consistency of the quantum-physical aspects of earlier work by Musha et
      al. 

PMID- 24875081
TI  - Learning from exceptional drug responders.

PMID- 24875080
TI  - Bioelectronic medicines: a research roadmap.

PMID- 24875082
TI  - Setback prompts rethink of latency-reversing strategy to eliminate HIV infection.

PMID- 24875086
TI  - Deal watch: Roles and strategies for health foundations in public-private
      partnerships.

PMID- 24875087
TI  - Trial watch: Lung cancer trial aims to bolster personalized medicine.

PMID- 24875088
TI  - Lamb chopped: Dolly not patent eligible.

PMID- 24875091
TI  - An audience with Tatiana Prowell. Interviewed by Asher Mullard.

PMID- 24875092
TI  - Randomised controlled trial and health economic evaluation of the impact of
      diagnostic testing for influenza, respiratory syncytial virus and Streptococcus
      pneumoniae infection on the management of acute admissions in the elderly and
      high-risk 18- to 64-year-olds.
AB  - BACKGROUND: Western industrialised nations face a large increase in the number of
      older people. People over the age of 60 years account for almost half of the 16.8
      million hospital admissions in England from 2009 to 2010. During 2009-10,
      respiratory infections accounted for approximately 1 in 30 hospital admissions
      and 1 in 20 of the 51.5 million bed-days. OBJECTIVE: To determine the diagnostic
      accuracy and clinical effectiveness and cost-effectiveness of rapid molecular and
      near-patient diagnostic tests for influenza, respiratory syncytial virus (RSV)
      and Streptococcus pneumoniae infections in comparison with traditional laboratory
      culture. METHODS: We carried out a randomised controlled trial (RCT) to evaluate
      impact on prescribing and clinical outcomes of point-of-care tests (POCTs) for
      influenza A and B and pneumococcal infection, reverse transcriptase-polymerase
      chain reaction (RT-PCR) tests for influenza A and B and RSV A and B, and
      conventional culture for these pathogens. We evaluated diagnostic accuracy of
      POCTs for influenza and pneumococcal infection, RT-PCR for influenza and sputum
      culture for S. pneumoniae using samples collected during the RCT. We did a
      systematic review and meta-analysis of POCTs for influenza A and B. We evaluated
      ease and speed of use of each test, process outcomes and cost-effectiveness.
      RESULTS: There was no evidence of association between diagnostic group and
      prescribing or clinical outcomes. Using PCR as 'gold standard', Quidel Influenza
      A + B POCT detected 24.4% [95% confidence interval (CI) 16.0% to 34.6%] of
      influenza infections (specificity 99.7%, 95% CI 99.2% to 99.9%); viral culture
      detected 21.6% (95% CI 13.5% to 31.6%; specificity 99.8%, 95% CI 99.4% to 100%).
      Using blood culture as 'gold standard', BinaxNOW pneumococcal POCT detected 57.1%
      (95% CI 18.4% to 90.1%) of pneumococcal infections (specificity 92.5%; 95% CI
      90.6% to 94.1%); sputum culture detected 100% (95% CI 2.5% to 100%; specificity
      97.2%, 95% CI 94.3% to 98.9%). Overall, pooled estimates of sensitivity and
      specificity of POCTs for influenza from the literature were 74% (95% CI 67% to
      80%) and 99% (95% CI 98% to 99%), respectively. Median intervals from specimen
      collection to test result were 15 minutes [interquartile range (IQR) 10-23
      minutes) for Quidel Influenza A + B POCT, 20 minutes (IQR 15-30 minutes) for
      BinaxNOW pneumococcal POCT, 50.8 hours (IQR 44.3-92.6 hours) for semi-nested
      conventional PCR, 29.2 hours (IQR 26-46.9 hours) for real-time PCR, 629.6 hours
      (IQR 262.5-846.7 hours) for culture of influenza and 84.4 hours (IQR 70.7-137.8
      hours) and 71.4 hours (IQR 69.15-84.0 hours) for culture of S. pneumoniae in
      blood and sputum, respectively. Both POCTs were rated straightforward and
      undemanding; blood culture was moderately complex and all other tests were
      complex. Costs and quality-adjusted life-years (QALYs) of each diagnostic
      strategy were similar. Incrementally, PCR was most cost-effective (78.3%
      probability at a willingness to pay of L20,000/QALY). Few patients were admitted
      within a timescale conducive to treatment with a neuraminidase inhibitor
      according to National Institute for Health and Care Excellence guidance.
      LIMITATIONS: The accuracy study was limited by inadequate gold standards.
      CONCLUSIONS: All tests had limitations. We found no evidence that POCTs for
      influenza or S. pneumoniae, or PCR for influenza or RSV influenced antimicrobial
      prescribing or clinical outcomes. The total costs and QALYs of each diagnostic
      strategy were similar, although, incrementally, PCR was the most cost-effective
      strategy. The analysis does not support routine use of POCTs for either influenza
      or pneumococcal antigen for adults presenting with acute cardiopulmonary
      conditions, but suggests that conventional viral culture for clinical diagnosis
      should be replaced by PCR. TRIAL REGISTRATION: Current Controlled Trials
      ISRCTN21521552. FUNDING: This project was funded by the NIHR Health Technology
      Assessment programme and will be published in full in Health Technology
      Assessment; Vol. 18, No. 36. See the NIHR Journals Library website for further
      project information.

PMID- 24875093
TI  - Hearing loss and dementia - who is listening?

PMID- 24875094
TI  - Role of retinoic acid receptor (RAR) signaling in post-natal male germ cell
      differentiation.
AB  - All-trans retinoic acid (atRA), the active metabolite of vitamin A, plays
      critical functions in spermatogenesis, a complex, highly organized and regulated
      process comprising three phases. During the proliferative phase, undifferentiated
      spermatogonia divide to maintain a stem cell population and expand a progenitor
      cell population, of which a fraction enters the differentiation pathway yielding
      primary spermatocytes. During the meiotic phase, primary spermatocytes undergo
      recombination, segregation and reduction by half of chromosomes to produce
      haploid round spermatids. During the morphogenetic, post-meiotic phase,
      spermatids differentiate and elongate to ultimately form spermatozoa. Studies
      performed during the past 20 years have significantly improved our knowledge on
      the location of the proteins transducing the atRA signal, on the target genes of
      atRA and on its mechanism of action. This article is part of a Special Issue
      entitled: Nuclear receptors in animal development.

PMID- 24875095
TI  - Androgens and mammalian male reproductive tract development.
AB  - One of the main functions of androgen is in the sexually dimorphic development of
      the male reproductive tissues. During embryogenesis, androgen determines the
      morphogenesis of male specific organs, such as the epididymis, seminal vesicle,
      prostate and penis. Despite the critical function of androgens in
      masculinization, the downstream molecular mechanisms of androgen signaling are
      poorly understood. Tissue recombination experiments and tissue specific androgen
      receptor (AR) knockout mouse studies have revealed epithelial or mesenchymal
      specific androgen-AR signaling functions. These findings also indicate that
      epithelial-mesenchymal interactions are a key feature of AR specific activity,
      and paracrine growth factor action may mediate some of the effects of androgens.
      This review focuses on mouse models showing the interactions of androgen and
      growth factor pathways that promote the sexual differentiation of reproductive
      organs. Recent studies investigating context dependent AR target genes are also
      discussed. This article is part of a Special Issue entitled: Nuclear receptors in
      animal development. 

PMID- 24875096
TI  - Dynamic alterations in Hippo signaling pathway and YAP activation during liver
      regeneration.
AB  - The Hippo signaling pathway has been implicated in mammalian organ size
      regulation and tumor suppression. Specifically, the Hippo pathway plays a
      critical role regulating the activity of transcriptional coactivator Yes
      associated protein (YAP), which modulates a proliferative transcriptional
      program. Recent investigations have demonstrated that while this pathway is
      activated in quiescent livers, its inhibition leads to liver overgrowth and
      tumorigenesis. However, the role of the Hippo pathway during the natural process
      of liver regeneration remains unknown. Here we investigated alterations in the
      Hippo signaling pathway and YAP activation during liver regeneration using a 70%
      partial hepatectomy (PH) rat model. Our results indicate an increase in YAP
      activation by 1 day following PH as demonstrated by increased YAP nuclear
      localization and increased YAP target gene expression. Investigation of the Hippo
      pathway revealed a decrease in the activation of core kinases Mst1/2 by 1 day as
      well as Lats1/2 and its adapter protein Mob1 by 3 days following PH. Evaluation
      of liver-to-body weight ratios indicated that the liver reaches its near normal
      size by 7 days following PH, which correlated with a return to baseline YAP
      nuclear levels and target gene expression. Additionally, when liver size was
      restored, Mst1/2 kinase activation returned to levels observed in quiescent
      livers indicating reactivation of the Hippo signaling pathway. These findings
      illustrate the dynamic changes in the Hippo signaling pathway and YAP activation
      during liver regeneration, which stabilize when the liver-to-body weight ratio
      reaches homeostatic levels. 

PMID- 24875097
TI  - Glugacon-like peptide-2: broad receptor expression, limited therapeutic effect on
      intestinal inflammation and novel role in liver regeneration.
AB  - The glucagon-like peptide 2 (GLP-2) is an intestinotrophic hormone with growth
      promoting and anti-inflammatory actions. However, the full biological functions
      of GLP-2 and the localization of its receptor (GLP-2R) remain controversial.
      Among cell lines tested, the expression of GLP-2R transcript was detected in
      human colonic myofibroblasts (CCD-18Co) and in primary culture of rat enteric
      nervous system but not in intestinal epithelial cell lines, lymphocytes,
      monocytes, or endothelial cells. Surprisingly, GLP-2R was expressed in murine
      (GLUTag), but not human (NCI-H716) enteroendocrine cells. The screening of GLP-2R
      mRNA in mice organs revealed an increasing gradient of GLP-2R toward the distal
      gut. An unexpected expression was detected in the mesenteric fat, mesenteric
      lymph nodes, bladder, spleen, and liver, particularly in hepatocytes. In two mice
      models of trinitrobenzene sulfonic acid (TNBS)- and dextran sulfate sodium (DSS)
      induced colitis, the colonic expression of GLP-2R mRNA was decreased by 60%
      compared with control mice. Also, GLP-2R mRNA was significantly downregulated in
      intestinal tissues of inflammatory bowel disease patients. Therapeutically, GLP-2
      showed a weak restorative effect on intestinal inflammation during TNBS-induced
      colitis as assessed by macroscopic score and inflammatory markers. Finally, GLP-2
      treatment accelerated mouse liver regeneration following partial hepatectomy as
      assessed by histological and molecular analyses. In conclusion, the limited
      therapeutic effect of GLP-2 on colonic inflammation dampens its utility in the
      management of severe inflammatory intestinal disorders. However, the role of GLP
      2 in liver regeneration is a novelty that might introduce GLP-2 into the
      management of liver diseases and emphasizes on the importance of elucidating
      other extraintestinal functions of GLP-2. 

PMID- 24875099
TI  - Activation of HIF-1alpha does not increase intestinal tumorigenesis.
AB  - The hypoxic response is mediated by two transcription factors, hypoxia-inducible
      factor (HIF)-1alpha and HIF-2alpha. These highly homologous transcription factors
      are induced in hypoxic foci and regulate cell metabolism, angiogenesis, cell
      proliferation, and cell survival. HIF-1alpha and HIF-2alpha are activated early
      in cancer progression and are important in several aspects of tumor biology. HIF
      1alpha and HIF-2alpha have overlapping and distinct functions. In the intestine,
      activation of HIF-2alpha increases inflammation and colon carcinogenesis in mouse
      models. Interestingly, in ischemic and inflammatory diseases of the intestine,
      activation of HIF-1alpha is beneficial and can reduce intestinal inflammation.
      HIF-1alpha is a critical transcription factor regulating epithelial barrier
      function following inflammation. The beneficial value of pharmacological agents
      that chronically activate HIF-1alpha is decreased due to the tumorigenic
      potential of HIFs. The present study tested the hypothesis that chronic
      activation of HIF-1alpha may enhance colon tumorigenesis. Two models of colon
      cancer were assessed, a sporadic and a colitis-associated colon cancer model.
      Activation of HIF-1alpha in intestinal epithelial cells does not increase
      carcinogenesis or progression of colon cancer. Together, the data provide proof
      of principle that pharmacological activation of HIF-1alpha could be a safe
      therapeutic strategy for inflammatory bowel disease. 

PMID- 24875098
TI  - Animal models of gastrointestinal and liver diseases. New mouse models for
      studying dietary prevention of colorectal cancer.
AB  - Colorectal cancer is a heterogeneous disease that is one of the major causes of
      cancer death in the U.S. There is evidence that lifestyle factors like diet can
      modulate the course of this disease. Demonstrating the benefit and mechanism of
      action of dietary interventions against colon cancer will require studies in
      preclinical models. Many mouse models have been developed to study colon cancer
      but no single model can reflect all types of colon cancer in terms of molecular
      etiology. In addition, many models develop only low-grade cancers and are
      confounded by development of the disease outside of the colon. This review will
      discuss how mice can be used to model human colon cancer and it will describe a
      variety of new mouse models that develop colon-restricted cancer as well as more
      advanced phenotypes for studies of late-state disease. 

PMID- 24875101
TI  - CD8+ T lymphocyte response against extrahepatic biliary epithelium is activated
      by epitopes within NSP4 in experimental biliary atresia.
AB  - Interferon (IFN)-gamma-driven and CD8+ T cell-dependent inflammatory injury to
      extrahepatic biliary epithelium (EHBE) is likely to be involved in the
      development of biliary atresia (BA). We previously showed that viral protein NSP4
      is the pathogenic immunogen that causes biliary injury in BA. In this study, NSP4
      or four synthetic NSP4 (NSP4(157-170), NSP4(144-152), NSP4(93-110), NSP4(24-32))
      identified by computer analysis as candidate CD8+ T cell epitopes were injected
      into neonatal mice. The pathogenic NSP4 epitopes were confirmed by studying
      extrahepatic bile duct injury, IFN-gamma release and CD8+ T cell response against
      EHBE. The results revealed, at 7 days postinjection, inoculation of glutathione S
      transferase (GST)-NSP4 caused EHBE injury and BA in neonatal mice. At 7 or 14
      days postinject, inoculation of GST-NSP4, NSP4(144-152), or NSP4(157-170)
      increased IFN-gamma release by CD8+ T cells, elevated the population of hepatic
      memory CD8+ T cells, and augmented cytotoxicity of CD8+ T cells to rhesus
      rotavirus (RRV)-infected or naive EHBE cells. Furthermore, depletion of CD8+ T
      cells in mice abrogated the elevation of GST-NSP4-induced serum IFN-gamma.
      Lastly, parenteral immunization of mouse dams with GST-NSP4, NSP4(144-152), or
      NSP4(157-170) decreased the incidence of RRV-induced BA in their offspring.
      Overall, this study reports the CD8+ T cell response against EHBE is activated by
      epitopes within rotavirus NSP4 in experimental BA. Neonatal passive immunization
      by maternal vaccination against NSP4(144-152) or NSP4(157-170) is effective in
      protecting neonates from developing RRV-related BA.

PMID- 24875100
TI  - Increased acid responsiveness in vagal sensory neurons in a guinea pig model of
      eosinophilic esophagitis.
AB  - Eosinophilic esophagitis (EoE) is characterized with eosinophils and mast cells
      predominated allergic inflammation in the esophagus and present with esophageal
      dysfunctions such as dysphagia, food impaction, and heartburn. However, the
      underlying mechanism of esophageal dysfunctions is unclear. This study aims to
      determine whether neurons in the vagal sensory ganglia are modulated in a guinea
      pig model of EoE. Animals were actively sensitized by ovalbumin (OVA) and then
      challenged with aerosol OVA inhalation for 2 wk. This results in a mild
      esophagitis with increases in mast cells and eosinophils in the esophageal wall.
      Vagal nodose and jugular neurons were disassociated, and their responses to acid,
      capsaicin, and transient receptor potential vanilloid type 1 (TRPV1) antagonist
      AMG-9810 were studied by calcium imaging and whole cell patch-clamp recording.
      Compared with naive animals, antigen challenge significantly increased acid
      responsiveness in both nodose and jugular neurons. Their responses to capsaicin
      were also increased after antigen challenge. AMG-9810, at a concentration that
      blocked capsaicin-evoked calcium influx, abolished the increase in acid-induced
      activation in both nodose and jugular neurons. Vagotomy strongly attenuated those
      increased responses of nodose and jugular neurons to both acid and capsaicin
      induced by antigen challenge. These data for the first time demonstrated that
      prolonged antigen challenge significantly increases acid responsiveness in vagal
      nodose and jugular ganglia neurons. This sensitization effect is mediated largely
      through TRPV1 and initiated at sensory nerve endings in the peripheral tissues.
      Allergen-induced enhancement of responsiveness to noxious stimulation by acid in
      sensory nerve may contribute to the development of esophageal dysfunctions such
      as heartburn in EoE. 

PMID- 24875103
TI  - RANTES (CCL5) reduces glucose-dependent secretion of glucagon-like peptides 1 and
      2 and impairs glucose-induced insulin secretion in mice.
AB  - Type 2 diabetes is associated with elevated circulating levels of the chemokine
      RANTES and with decreased plasma levels of the incretin hormone glucagon-like
      peptide 1 (GLP-1). GLP-1 is a peptide secreted from intestinal L-cells upon
      nutrient ingestion. It enhances insulin secretion from pancreatic beta-cells and
      protects from beta-cell loss but also promotes satiety and weight loss. In search
      of chemokines that may reduce GLP-1 secretion we identified RANTES and show that
      it reduces glucose-stimulated GLP-1 secretion in the human enteroendocrine cell
      line NCI-H716, blocked by the antagonist Met-RANTES, and in vivo in mice. RANTES
      exposure to mouse intestinal tissues lowers transport function of the intestinal
      glucose transporter SGLT1, and administration in mice reduces plasma GLP-1 and
      GLP-2 levels after an oral glucose load and thereby impairs insulin secretion.
      These data show that RANTES is involved in altered secretion of glucagon-like
      peptide hormones most probably acting through SGLT1, and our study identifies the
      RANTES-receptor CCR1 as a potential target in diabetes therapy. 

PMID- 24875105
TI  - Ephemeral existence of a single catecholamine synthetic enzyme in the olfactory
      placode and the spinal cord of the embryonic rat.
AB  - The distribution of three catecholamine synthetic enzymes (tyrosine hydroxylase,
      l-aromatic acid decarboxylase and dopamine beta-hydroxylase), of the
      catecholamines themselves (dopamine and noradrenaline) and of a marker for
      neuronal intermediate filaments (neurofilament) was investigated in the embryonic
      rat using immunohistochemical and histofluorescence methods. At early stages of
      gestation (days 11-13), large numbers of tyrosine hydroxylase immunoreactive
      cells and fibres were apparent in the ventro-lateral spinal cord, and in and
      around the olfactory placode. In both cases, tyrosine hydroxylase positive fibres
      coursed between the proliferative layer and the surrounding mesenchyme,
      indicating the considerable degree of morphological differentiation. The similar
      disposition of neurofilament-like immunoreactivity in the same regions suggested
      that the tyrosine hydroxylase containing structures were neuronal. Within 2-3
      days of their first manifestation, the tyrosine hydroxylase immunoreactive
      neurons disappeared. In the spinal cord, this coincided with their migration out
      of the mantle layer. Over this same period, neither of the other enzymes involved
      in the synthesis of noradrenaline, namely l-aromatic acid decarboxylase and
      dopamine beta-hydroxylase, nor dopamine and noradrenaline themselves, could be
      detected. It is concluded that some neurons in the olfactory placodal region and
      the ventrolateral spinal cord temporarily express a single specifically
      catecholaminergic enzyme, tyrosine hydroxylase, which is not utilized at that
      time in catecholamine synthesis. It is suggested that the control of
      transcription of the gene coding for tyrosine hydroxylase is independent of that
      for other catecholaminergic synthetic enzymes. 

PMID- 24875102
TI  - Human FABP1 T94A variant impacts fatty acid metabolism and PPAR-alpha activation
      in cultured human female hepatocytes.
AB  - Although human liver fatty acid-binding protein (FABP1) T94A variant has been
      associated with nonalcoholic fatty liver disease and reduced ability of
      fenofibrate to lower serum triglycerides (TG) to target levels, molecular events
      leading to this phenotype are poorly understood. Cultured primary hepatocytes
      from female human subjects expressing the FABP1 T94A variant exhibited increased
      neutral lipid (TG, cholesteryl ester) accumulation associated with (1)
      upregulation of total FABP1, a key protein stimulating mitochondrial glycerol-3
      phosphate acyltransferase (GPAM), the rate-limiting enzyme in lipogenesis; (2)
      increased mRNA expression of key enzymes in lipogenesis (GPAM, LPIN2) in
      heterozygotes; (3) decreased mRNA expression of microsomal triglyceride transfer
      protein; (4) increased secretion of ApoB100 but not TG; (5) decreased long-chain
      fatty acid (LCFA) beta-oxidation. TG accumulation was not due to any increase in
      LCFA uptake, de novo lipogenesis, or the alternate monoacylglycerol O
      acyltransferase pathway in lipogenesis. Despite increased expression of total
      FABP1 mRNA and protein, fenofibrate-mediated FABP1 redistribution to nuclei and
      ligand-induced peroxisome proliferator-activated receptor (PPAR-alpha)
      transcription of LCFA beta-oxidative enzymes (carnitine palmitoyltransferase 1A,
      carnitine palmitoyltransferase 2, and acyl-coenzyme A oxidase 1, palmitoyl) were
      attenuated in FABP1 T94A hepatocytes. Although the phenotype of FABP1 T94A
      variant human hepatocytes exhibits some similarities to that of FABP1-null or
      PPAR-alpha-null hepatocytes and mice, expression of FABP1 T94A variant did not
      abolish or reduce ligand binding. Thus the FABP1 T94A variant represents an
      altered/reduced function mutation resulting in TG accumulation.

PMID- 24875106
TI  - Development of binding sites for vasoactive intestinal polypeptide in mouse
      cerebral cortex and cultured cortical neurons.
AB  - Binding sites for vasoactive intestinal polypeptide (VIP) and the content of
      immunoreactive VIP were measured in the foetal and neonatal mouse brain cortex
      and primary cultures of foetal murine brain-cortical neurons and astrocytes. The
      amount of cortical VIP binding sites and the concentration of immunoreactive VIP
      were low before birth, but increased postnatally reaching adult level at about 3
      weeks of age. In cultures, a similar rise in neuronal binding sites occurred
      after 10 days, whereas the VIP concentration remained lower than in adult brain
      cortex. No binding sites or immunoreactive VIP could be detected in cultured
      astrocytes. The VIP binding sites were heterogeneous both in developing brain
      cortex and cultured neurons, and consisted of two classes of binding sites. The
      high affinity constants (2.5-2.9 nM) as well as low affinity constants (50-76 nM)
      were unchanged during the development, whereas the number of binding sites
      increased. In cultured neurons the binding constants were similar to those found
      in the adult mouse brain cortex. The peptide specificity for the VIP binding was
      similar in brain cortex and neuronal culture. In conclusion, the maturation of
      murine brain cortical neurons is accompanied by the development of synaptosomal
      VIP receptors in support of the neurotransmitter function of VIP. 

PMID- 24875107
TI  - Morphological and biochemical maturation of rat astroglial cells grown in a
      chemically defined medium: Influence of an astroglial growth factor.
AB  - Astroglial cells from cerebral hemispheres of newborn rats were cultured for 5
      days in Waymouth's MD 705/1 medium containing 10% fetal calf serum. Thereafter,
      cells were grown in a chemically defined medium consisting of basal Waymouth's
      medium supplemented with insulin (5 MUg/ml) and fatty acid free bovine serum
      albumin (0.5 mg/ml). The cells underwent morphological and biochemical
      development over a period of 28 days. The changes in the amount of glial
      fibrillary acidic protein indicated a development of gliofilaments. The level of
      S100 protein increased during the entire culture period, while glutamine
      synthetase activity remained low and relatively constant. The addition of an
      astroglial growth factor, partially purified from bovine brain soluble extract,
      stimulated the morphological maturation of the astroglial cells. The cells
      extended cytoplasmic processes and resembled mature astrocytes. At the
      ultrastructural level an increase in free ribosomes was observed and the
      intermediate filaments became organized into large bundles. The amount of glial
      fibrillary acidic protein was not significantly increased, but the level of S100
      protein and the glutamine synthetase activity were greatly enhanced. Our results
      indicate that astroglial cells undergo limited maturation in the chemically
      defined medium and that this process is positively affected by the astroglial
      growth factor. 

PMID- 24875108
TI  - Gangliosides induce microfilament-dependent changes in membrane surface activity
      of Neuro-2a neuroblastoma cells.
AB  - Exogenous mixtures of bovine brain gangliosides (BBG) initiated a rapid series of
      sequential changes in surface activity in Neuro-2a neuroblastoma cells. These
      changes were characterized by the formation of microvilli, ridge-like projections
      and ruffled membranes within l min of BBG exposure. A maximum number of
      microvilli was reached after 10 min exposure and disappeared by 30 min. Ruffled
      membranes were most prominent within 5 min, but were still present after 60 min.
      These surface changes were accompanied by the formation of a thick subcortical
      meshwork of microfilaments which formed the cores of the microvilli and ruffled
      membranes. The simultaneous treatment of cells with BBG and an agent known to
      disrupt microfilaments (cytochalasin D) inhibited the formation of both
      microvilli and ruffles. In contrast, the simultaneous application of BBG and
      agents affecting microtubule polymerization (Colcemid and taxol) did not inhibit
      the formation of these surface structures. Treatment of Neuro-2a cells with
      cyclic AMP (cAMP) analogs (dibutyryl cAMP and 8-bromo cAMP) induced a similar
      series of surface changes which were inhibited by cytochalasin D. Furthermore,
      these surface changes may be specific to cAMP since neither cGMP analogs
      (dibutyryl cGMP and 8-bromo cGMP) nor 5'AMP induced surface changes. We propose
      that the initial membrane response to exogenous gangliosides is mediated by a
      microfilament-dependent mechanism. The basic similarities in surface responses
      elicited by BBG and cAMP analogs suggest that the effects of gangliosides on
      surface activity may be induced in part by a cAMP-dependent mechanism. 

PMID- 24875109
TI  - Interplexiform, horizontal and bipolar-like cells of the rabbit retina take up
      exogenous serotonin during early developmental stages.
AB  - A subpopulation of amacrine cells which have the ability to take up exogenous
      serotonin occur in the rabbit retina at all stages during postnatal development.
      However, during the initial stages of the retina's development some serotonin
      accumulating neurons are also associated with the outer plexiform layer in the
      form of interplexiform and/or bipolar and/or horizontal cells. These neurons
      could have an additional function of their own or simply be misplaced serotonin
      accumulating neurons destined to degenerate in the process of synaptogenesis. 

PMID- 24875104
TI  - Extracellular adenosine regulates colitis through effects on lymphoid and
      nonlymphoid cells.
AB  - Adenosine is a purine metabolite that can mediate anti-inflammatory responses in
      the digestive tract through the A(2A) adenosine receptor (A(2A)AR). We examined
      the role of this receptor in the control of inflammation in the adoptive transfer
      model of colitis. Infection of A(2A)AR(-/-) mice with Helicobacter hepaticus
      increased colonic inflammation scores compared with uninfected A(2A)AR controls.
      Comparison of T cell subsets in wild-type and A(2A)AR(-/-) mice revealed
      differences in markers associated with activated helper T (Th) cells and
      regulatory T (Treg) cells. Previous studies showed that expression of A(2A)AR on
      CD45RB(HI) and CD45RB(LO) Th cells is essential for the proper regulation of
      colonic inflammation. Adoptive transfer of CD45RB(HI) with CD45RB(LO) from wild
      type mice into RAG1(-/-)/A(2A)AR(-/-) mice induced severe disease within 3 wk,
      although transfer of the same subsets into RAG1(-/-) mice does not induce
      colitis. This suggests that the presence of A(2A)AR on recipient cells is also
      important for controlling colitis. To investigate the role of A(2A)AR in myeloid
      cells, chimeric recipients were generated by injection of bone marrow from RAG1(
      /-) or RAG1(-/-)/A(2A)AR(-/-) mice into irradiated RAG1(-/-) mice. After adoptive
      transfer, these recipients did not develop colitis, regardless of A(2A)AR
      expression by the donor. Together, our results suggest that the control of
      inflammation in vivo is dependent on A(2A)AR signaling through multiple cell
      types that collaborate in the regulation of colitis by responding to
      extracellular adenosine.

PMID- 24875110
TI  - Postnatal development of calmodulin and calmodulin-dependent phosphodiesterase in
      different regions of the rat central nervous system.
AB  - We have studied the concentration of calmodulin and phosphodiesterase (cAMP high
      Km) in five different parts of the rat central nervous system (hemispheres,
      cerebellum, diencephalon, brain stem and spinal cord) during postnatal
      development (5, 10, 15, 20, 30 and 45 days after birth). The concentration of the
      enzyme and its regulatory protein were independent, so that no correlation could
      be established between them. In most structures, calmodulin concentration tended
      to decrease with age, while phosphodiesterase increased or remained at similar
      values during the time studied. The calmodulin inhibitor trifluoperazine,
      inhibited phosphodiesterase activity to different degrees, depending on the
      structure, and age. Hemispheres, diencephalon and brain stem showed maximal
      inhibition (approximately 95-65% of control). In these structures, inhibition was
      higher in older animals. By contrast, cerebellum and spinal cord PDE was less
      inhibited by trifluoperazine (65-50% of control), and inhibition was independent
      of age. The validation of a method for both calmodulin and phosphodiesterase
      assay, using a modification of established methods, is also reported. 

PMID- 24875111
TI  - Effects of thyroid deficiency on the development of cholinergic, GABA,
      dopaminergic and glutamate neuron markers and DNA concentrations in the rat
      corpus striatum.
AB  - The effects of propylthiouracil (PTU)-induced thyroid deficiency on the postnatal
      development of synaptic markers for cholinergic, GABA, dopaminergic and glutamate
      neurons in the rat corpus striatum were investigated. Similar effects were also
      assessed on beta-alanine uptake by fine prisms and on DNA concentrations in
      striatal samples from 3- and 6-week-old rats. Thyroid deficiency (Tx) in rats
      markedly impaired the development of choline acetyltransferase activity and
      [(3)H]spiroperidol and [(3)H]-glutamate binding capacities. In contrast, small
      but significant increases were evident in gamma-aminobutyric acid uptake and
      glutamate decarboxylase activity. beta-Alanine uptake, a possible glial marker,
      was increased by up to 50% in samples from the Tx rats compared to controls.
      Consistent with deficits in striatal weight and greater DNA concentrations in the
      striatum of the Tx rats those neuronal markers which showed impairments on a mg
      tissue basis manifest even greater impairments expressed per whole striatum.
      Present findings suggest differential effects on neuronal markers, with the
      greatest impairments in the presynaptic markers for cholinergic interneurons in
      striatum during neonatal thyroid deficiency. The differential sensitivity on
      neuronal markers of the relatively late onset of thyroid deficiency seems likely
      to reflect the timing of the morphological differentiation of cholinergic and the
      other neurons in striatum. 

PMID- 24875112
TI  - Regional [(3)H]acetylcholine and [(3)H]nicotine binding in developing mouse
      brain.
AB  - The postnatal development of nicotine-like binding sites in the cortex,
      hippocampus, midbrain and cerebellum of 3-, 7-, 12-, 17- and 30-day-old mice was
      studied. Two different nicotinic cholinergic ligands, namely [(3)H]acetylcholine
      ([(3)H]ACh) and [(3)H]nicotine ([(3)H]NIC) were used to detect the nicotine-like
      binding sites in in vitro binding assays. The postnatal development of the
      binding sites of [(3)H]NIC increased gradually with age in all brain regions
      studied. The [(3)H]ACh binding, on the other hand, showed a marked peak on day 12
      in the cerebellum and midbrain but did not change notably with age in the
      hippocampus and cortex, except for a slight temporary increase in the cortex on
      day 7. The time-course for the appearance of nicotinic binding sites as observed
      with [(3)H]ACh was found to be rather similar to that earlier described for
      [(3)H]alpha-bungarotoxin binding sites, whereas that for [(3)H]NIC differed from
      that described for other nicotinic ligands. 

PMID- 24875113
TI  - Increase in the number and volume of myenteric neurons in the adult rat.
AB  - In response to enhanced functional activity, only the larger neurons of the
      myenteric plexus incorporate thymidine. Their number, too, is increased. This
      phenomenon is not accompanied by proliferation. 

PMID- 24875115
TI  - Re: CT imaging of complications of catheter ablation for atrial fibrillation. A
      reply.

PMID- 24875116
TI  - Re: ECG-gated quiescent-interval single-shot MR angiography of the lower
      extremities: initial experience at 3 T.

PMID- 24875117
TI  - Re: ECG-gated quiescent-interval single-shot MR angiography of the lower
      extremities: initial experience at 3 T. A reply.

PMID- 24875118
TI  - Re: Small solid renal masses: characterization by diffusion-weighted MRI at 3 T.
      A reply.

PMID- 24875120
TI  - Small cell carcinoma of the gynecologic tract: a multifaceted spectrum of
      lesions.
AB  - OBJECTIVE: Small cell carcinoma (SmCC) of the female genital tract constitutes a
      diagnostic and clinical challenge given its rarity and the lack of standardized
      therapeutic approaches. Here we review the morphological, clinical and molecular
      features of gynecologic SmCCs and discuss potential areas for future research.
      METHODS: Data for this review article were identified by searches of PubMed,
      EMBASE and the Internet using the search terms "small cell carcinoma" or
      "neuroendocrine carcinoma" and "gynecologic", "uterine cervix", "cervix",
      "uterus", "endometrium", "ovary", "vagina", "fallopian tube" or "vulva", and
      research articles published in English between 1972 and February 2014 were
      included. RESULTS: SmCCs arising from different organs within the gynecologic
      tract share the same histopathologic characteristics, which closely resemble
      those of small cell lung carcinoma. The expression of at least one
      immunohistochemical neuroendocrine marker is a common finding. The uterine cervix
      is the most frequent site of SmCC in the female genital tract. HPV infection
      seems to play a role in the development of cervical SmCC but not in cancers of
      other gynecologic sites. FIGO stage is an established prognostic factor, in
      particular in SCCs of the cervix. Irrespective of the site, SmCCs of the
      gynecologic tract display an aggressive clinical behavior with few reported long
      term survivors. The therapeutic management includes surgery, radiotherapy and
      chemotherapy. CONCLUSIONS: Despite the potential differences in etiology and risk
      factors, SmCCs from different sites of the gynecologic tract have similar
      morphologic appearances and clinical behavior. Recent genomic analyses of small
      cell carcinoma of the lung have revealed potential driver genomic alterations. We
      posit that the comprehensive genomic characterization of gynecologic SmCCs may
      lead to the identification of markers that result in an improvement of diagnostic
      reproducibility of SmCCs of the gynecologic tract, and of molecular aberrations
      that may be exploited therapeutically in subgroups of the disease.

PMID- 24875119
TI  - Setting an upper limit on the myoglobin iron(IV)hydroxide pK(a): insight into
      axial ligand tuning in heme protein catalysis.
AB  - To provide insight into the iron(IV)hydroxide pK(a) of histidine ligated heme
      proteins, we have probed the active site of myoglobin compound II over the pH
      range of 3.9-9.5, using EXAFS, Mossbauer, and resonance Raman spectroscopies. We
      find no indication of ferryl protonation over this pH range, allowing us to set
      an upper limit of 2.7 on the iron(IV)hydroxide pK(a) in myoglobin. Together with
      the recent determination of an iron(IV)hydroxide pK(a) ~ 12 in the thiolate
      ligated heme enzyme cytochrome P450, this result provides insight into Nature's
      ability to tune catalytic function through its choice of axial ligand.

PMID- 24875121
TI  - Younger age distribution of cervical cancer incidence among survivors of
      pediatric and young adult cancers.
AB  - BACKGROUND: Pediatric and young adult (PAYA) cancer survivors may have an earlier
      onset of chronic diseases compared with the general population. We compared the
      age at cervical cancer diagnosis between PAYA cancer survivors and females in the
      general US population. METHODS: We used longitudinal data from 9 population-based
      registries of the Surveillance, Epidemiology, and End Results program collected
      between 1973 and 2010. PAYA cancer survivors were females diagnosed with any
      cancer before age 30 years, survived at least 5 years post-diagnosis, and were
      subsequently diagnosed with invasive cervical cancer (n=46). The general US
      population comprised females who were diagnosed with invasive cervical cancer as
      the primary malignancy (n=26,956). We estimated the difference in median age at
      diagnosis (beta50) and bootstrap 95% confidence limits (CL) of invasive cervical
      cancer after adjustment for year of diagnosis and race. RESULTS: The median age
      at diagnosis of invasive cervical cancer was 33 years for female PAYA cancer
      survivors and 40 years for females in the general US population (beta50=-7.0, 95%
      CL: -11, -3.2). Similar differences were observed across subgroups of stage and
      histologic subtype of invasive cervical cancer. CONCLUSION: Our results suggest
      that PAYA cancer survivors are diagnosed with invasive cervical cancer at a
      substantially younger age compared with females without a prior cancer diagnosis
      in the general US population. This issue warrants further study, and could have
      implications for determining age at initiation or frequency of cervical cancer
      screening if younger age at diagnosis is attributable to an underlying biological
      phenomenon.

PMID- 24875122
TI  - Is venous thromboprophylaxis necessary in patients undergoing minimally invasive
      surgery for a gynecologic malignancy?
AB  - OBJECTIVES: Current recommendations for the use of venous thromboprophylaxis in
      patients undergoing minimally invasive surgery (MIS) for a gynecologic malignancy
      are derived from patients undergoing open surgery. Our objective was to determine
      the 30-day prevalence of symptomatic venous thromboembolism (VTE) after
      laparoscopic gynecologic oncology procedures in patients who received no
      thromboprophylaxis. METHODS: Between January 2006 and September 2013, women who
      underwent MIS for endometrial, cervical or ovarian cancer at a single institution
      were included. Data on patient demographics, diagnosis, comorbidities,
      perioperative characteristics, use of thromboprophylaxis, and diagnosis of VTE
      were collected retrospectively. RESULTS: Of the 419 patients who underwent MIS
      for a gynecologic cancer, 352 (84%) received no VTE prophylaxis. At least a total
      laparoscopic hysterectomy (simple or radical) or pelvic lymph node dissection was
      performed in 95% of these patients. The median length of surgery was 137 min and
      95% of patients were discharged home within 1 day of surgery. The rate of VTE in
      the 352 untreated patients was 0.57% (1 pulmonary embolism and 1 deep vein
      thrombosis). There were no VTE diagnosed within 30 days of surgery in the 67
      patients who received anticoagulant thromboprophylaxis. CONCLUSION: The rate of
      VTE is low in patients undergoing minimally invasive surgery for a gynecologic
      malignancy despite no VTE prophylaxis. The benefits of routine use of VTE
      prophylaxis in this population are questionable.

PMID- 24875123
TI  - Quantifying the risk of recurrence and death in stage III (FIGO 2009) endometrial
      cancer.
AB  - OBJECTIVE: Advanced endometrial cancer patients comprise a heterogeneous group.
      This study assessed the association of clinicopathological factors with relapse
      and death from endometrial cancer. METHODS: Eligible patients were treated for
      stage III (FIGO 2009) endometrial adenocarcinoma, had peritoneal cytology
      performed, and had no gross residual disease post-operatively. RESULTS: Of 192
      patients, 59% were >=60 years old, 48% had >=50% myometrial invasion, 71%
      lymphovascular invasion, 25% cervical stromal invasion, 37% adnexal involvement,
      and 23% positive peritoneal cytology. High-grade histology (serous, clear cell,
      undifferentiated, or grade 3 endometrioid) was present in 45%. Pelvic
      lymphadenectomy was performed in 93% and para-aortic lymphadenectomy in 73%.
      Adjuvant chemotherapy and/or radiation therapy was administered to 93%. At a
      median follow-up of 42 months, the 5-year rate of relapse was 37% and of death
      from endometrial cancer was 30%. On multivariate analysis, both outcomes were
      associated with high-grade histology, positive peritoneal cytology, and deep
      myometrial invasion (p<=0.04). The cohort was divided into subgroups of patients
      with 0 (n=46), 1 (n=83), or >=2 (n=63) of these high-risk characteristics. The 5
      year relapse rate for patients with 0 risk factors was 13%, 1 risk factor was
      27%, and >=2 risk factors was 62% (p<0.001). The corresponding 5-year rates of
      death from endometrial cancer were 11%, 20%, and 56%, respectively (p<0.001).
      CONCLUSIONS: Stratification of stage III endometrial cancer according to high
      grade histology, positive peritoneal cytology, and deep myometrial invasion is
      useful for prognostication and may grant insight into the optimal treatment for
      specific subgroups of patients.

PMID- 24875124
TI  - Trends in incidence and survival of women with invasive vulvar cancer in the
      United States and Canada: a population-based study.
AB  - AIM: The aim of this study is to estimate trends in incidence and relative
      survival in women diagnosed with invasive squamous cell vulvar cancer in the
      United States (U.S.) and Canada over the periods of 1973-2010 for U.S. and 1992
      2008 for Canada. METHODS: We identified patients with primary invasive squamous
      cell vulvar cancers in the Surveillance, Epidemiology, and End Results cancer
      registry database and the Canadian Cancer Registry dataset. Women younger than 40
      years were excluded because of the small number of patients in this age group. A
      flexible parametric model was used to estimate two- and five-year relative
      survival ratios and excess mortality rate. RESULTS: In total 15,041 patients
      diagnosed with invasive squamous cell vulvar cancer were included in this
      analysis. The incidence rate of vulvar cancer increased in both U.S. and Canada.
      Two- and five-year relative survival ratios decreased over time for both
      countries, particularly for patients 80 years and over. CONCLUSIONS: The
      incidence rate of invasive vulvar cancer continued to increase in U.S. and Canada
      while its two- and five-year relative survival ratios gradually decreased for all
      age groups over the last few decades. Also, excess mortality rate reaches to its
      peak after about 6 months from diagnosis and then starts to decline. This is the
      first report that examine relative survival ratio for vulvar cancer in Canada and
      U.S. and serves as a basis for future similar studies.

PMID- 24875125
TI  - Effect of enzymatic orientation through the use of syringaldazine molecules on
      multiple multi-copper oxidase enzymes.
AB  - The effect of proper enzyme orientation at the electrode surface was explored for
      two multi-copper oxygen reducing enzymes: Bilirubin Oxidase (BOx) and Laccase
      (Lac). Simultaneous utilization of "tethering" agent (1-pyrenebutanoic acid,
      succinimidyl ester; PBSE), for stable enzyme immobilization, and syringaldazine
      (Syr), for enzyme orientation, of both Lac and BOx led to a notable enhancement
      of the electrode performance. For Lac cathodes tested in solution it was
      established that PBSE-Lac and PBSE-Syr-Lac modified cathodes demonstrated
      approximately 6 and 9 times increase in current density, respectively, compared
      to physically adsorbed and randomly oriented Lac cathodes. Further testing in
      solution utilizing BOx showed an even higher increase in achievable current
      densities, thus BOx was chosen for additional testing in air-breathing mode. In
      subsequent air-breathing experiments the incorporation of PBSE and Syr with BOx
      resulted in current densities of 0.65 +/- 0.1 mA cm(-2); 2.5 times higher when
      compared to an unmodified BOx cathode. A fully tethered/oriented BOx cathode was
      combined with a NAD-dependent Glucose Dehydrogenase anode for the fabrication of
      a complete enzymatic membraneless fuel cell. A maximum power of 1.03 +/- 0.06 mW
      cm(-2) was recorded for the complete fuel cell. The observed significant
      enhancement in the performance of "oriented" cathodes was a result of proper
      enzyme orientation, leading to facilitated enzyme/electrode interface
      interactions. 

PMID- 24875126
TI  - Design and synthesis of marine natural product-based 1H-indole-2,3-dione scaffold
      as a new antifouling/antibacterial agent against fouling bacteria.
AB  - Marine organisms such as seaweeds, sponges and corals protect their own surfaces
      from fouling by their high anesthetic, repellant, and settlement inhibition
      properties. Within the marine ecosystem, evolution has allowed for the
      development of certain antifouling properties. Isatin is a biologically active
      chemical produced by an Alteromonas sp. strain inhibiting the surface of embryos
      of the cardiean shrimp Palaemon macrodectylus, which protect them from the
      pathogenic fungus Lagenidium callinectes. In present study, an antibacterial
      activity of isatin and its synthetic analogues were evaluated against different
      fouling bacteria in order to explore the structure activity relationships for the
      first time. The synthesized compounds along with parent isatin were tested
      against different ecologically relevant marine microorganisms by using the Kirby
      Bauer disc diffusion method. Few synthetically modified isatin exhibited potent
      inhibitory activity at concentration of 2 MUg/disc against Planococcus
      donghaensis, Erythrobacter litoralis, Alivibrio salmonicida, Vibrio furnisii.
      Overall, the modified analogues showed stronger activity than the parent marine
      natural product (isatin) and hence 1H-indole-2,3-dione scaffold has immense
      potential as future antibacterial/antifouling candidate.

PMID- 24875127
TI  - miR-1271 regulates cisplatin resistance of human gastric cancer cell lines by
      targeting IGF1R, IRS1, mTOR, and BCL2.
AB  - Numerous studies showed that drug resistance of gastric cancer cells could be
      modulated by the abnormal expression of microRNAs (miRNAs) which target multiple
      cell signaling pathways. The possible function of miR-1271 in the formation of
      cisplatin resistance in gastric cancer cells has been investigated in this study.
      miR-1271 was significantly down-regulated in gastric cancer tissues and various
      gastric cancer cell lines. Moreover, it was down-regulated in the cisplatin
      resistant gastric cancer cell line SGC7901/cisplatin (DDP) and the down
      regulation of miR-1271 in SGC7901/DPP cells was accompanied by the up-regulation
      of insulin-like growth factor 1 receptor (IGF1R)/insulin receptor substrate 1
      (IRS1) pathway-related proteins, i.e., IGF1R, IRS1, serine/threonine-protein
      kinase mTOR (mTOR), and the apoptosis regulator Bcl-2 (BCL2), compared with the
      parental SGC7901 cells. Over-expression of miR-1271 sensitized SGC7901/DDP cells
      to cisplatin. Changes in the luciferase activity of reporter constructs harboring
      the 3'-untranslated region of the above proteins in SGC7901/DDP cells suggested
      that IGF1R, IRS1, mTOR, and BCL2 were target genes of miR-1271. Enforced miR-1271
      expression repressed the protein levels of its targets, inhibited proliferation
      of SGC7901/DDP cells, and sensitized SGC7901/DDP cells to DDP-induced apoptosis.
      Overall, on the basis of the results of our study, we proposed that miR-1271
      could regulate cisplatin resistance in human gastric cancer cells, at least
      partially, via targeting the IGF1R/IRS1 pathway.

PMID- 24875128
TI  - Design and development of oxazol-5-ones as potential partial PPAR-gamma agonist
      against cancer cell lines.
AB  - Recent era aims at developing safer partial Peroxisome proliferator-activated
      receptor-gamma (PPAR- gamma) agonists in order to dodge the toxicity issues
      related to full agonists. With a view to develop non-thiazolidinediones as
      partial PPAR-gamma agonists, novel analogues of oxazol-5-ones (3a-3q) were
      designed and virtually analyzed for their molecular and drug like properties. The
      newly synthesized compounds were further evaluated for their preliminary
      cytotoxicity in a panel of eight cancer cell lines using four concentrations at
      10- fold dilutions. Sulforhodamine B (SRB) protein assay was used to estimate
      cell stability or growth. All the compounds demonstrated distinct effect in the
      extent of cytotoxicity in the breast cancer cell line MCF-7 with 3g specifically
      exhibiting partial PPAR-gamma agonist activity and adipogenesis stimulating
      ability.

PMID- 24875129
TI  - Methicillin-resistant Staphylococcus aureus dacryoadenitis.
AB  - IMPORTANCE: Although classically thought to be primarily a nosocomial infection,
      the incidence of community-acquired methicillin-resistant Staphylococcus aureus
      (MRSA) is rising. In this series we report 3 cases of community-acquired MRSA
      acute dacryoadenitis in adults presenting within a 3-week period. OBSERVATIONS:
      All cases presented with pain and periocular erythema increasing over
      approximately 1 week. An S-shaped lid deformity was evident, and 2 of the 3 cases
      demonstrated multiple pustules/abscesses in the region of the lacrimal gland that
      were expressing purulent fluid into the superior fornix. Eye cultures yielded
      MRSA. Each case had complete clinical resolution with 2 to 4 days of intravenous
      vancomycin followed by 1 week of oral trimethoprim-sulfamethoxazole combination
      therapy. CONCLUSIONS AND RELEVANCE: These cases underscore the changing profile
      of MRSA infections, especially in the community-based setting. MRSA
      dacryoadenitis can be difficult to treat with standard therapeutic approaches and
      may progress to orbital cellulitis. We recommend a short admission for
      intravenous antibiotic therapy while bacterial sensitivities are being determined
      before transitioning to a dual-targeted oral antibiotic regimen.

PMID- 24875130
TI  - Transplantation of betacellulin-transduced islets improves glucose intolerance in
      diabetic mice.
AB  - Type 1 diabetes is an autoimmune disease caused by permanent destruction of
      insulin-producing pancreatic beta cells and requires lifelong exogenous insulin
      therapy. Recently, islet transplantation has been developed, and although there
      have been significant advances, this approach is not widely used clinically due
      to the poor survival rate of the engrafted islets. We hypothesized that improving
      survival of engrafted islets through ex vivo genetic engineering could be a novel
      strategy for successful islet transplantation. We transduced islets with
      adenoviruses expressing betacellulin, an epidermal growth factor receptor ligand,
      which promotes beta-cell growth and differentiation, and transplanted these
      islets under the renal capsule of streptozotocin-induced diabetic mice.
      Transplantation with betacellulin-transduced islets resulted in prolonged
      normoglycemia and improved glucose tolerance compared with those of control virus
      transduced islets. In addition, increased microvascular density was evident in
      the implanted islets, concomitant with increased endothelial von Willebrand
      factor immunoreactivity. Finally, cultured islets transduced with betacellulin
      displayed increased proliferation, reduced apoptosis and enhanced glucose
      stimulated insulin secretion in the presence of cytokines. These experiments
      suggest that transplantation with betacellulin-transduced islets extends islet
      survival and preserves functional islet mass, leading to a therapeutic benefit in
      type 1 diabetes. 

PMID- 24875131
TI  - In vitro 3D colon tumor penetrability of SRJ09, a new anti-cancer andrographolide
      analog.
AB  - Limited tumor penetrability of anti-cancer drugs is recognized as one of the
      major factors that lead to poor anti-tumor activity. SRJ09 (3,19-(2
      bromobenzylidene) andrographolide) has been identified as a lead anti-cancer
      agent for colon cancer. Recently, this compound was shown by us to be a mutant K
      Ras binder. In this present study, the penetrability of SRJ09 through the DLD-1
      colon cancer multicell layer (MCL) was evaluated. The amount of SRJ09 that
      penetrated through the MCL was quantitated by utilizing high performance liquid
      chromatography (HPLC). Histopathological staining was used to visualize the
      morphology of MCL. A chemosensitivity assay was performed to assess the anti
      cancer activity of SRJ09 in DLD-1 cells. SRJ09 was able to penetrate through DLD
      1 MCL and is inversely proportional with the MCL thickness. The flow rates for
      SRJ09 through MCL were 0.90 +/- 0.20 MUM/min/cm(2) and 0.56 +/- 0.06
      MUM/min/cm(2) for days 1 and 5, respectively, which are better than doxorubicin.
      Histopathological examination revealed that the integrity of the DLD-1 MCL was
      retained and no visible damage was inflicted on the cell membrane, confirming the
      penetration of SRJ09 was by diffusion. Short term exposure (1 h) in DLD-1 cells
      demonstrated SRJ09 had IC50 of 41 MUM which was approximately 4-folds lower than
      andrographolide, the parent compound of SRJ09. In conclusion, SRJ09 successfully
      penetrated through DLD-1 MCL by diffusion and emerged as a potential candidate to
      be developed as a clinically viable anti-colon cancer drug.

PMID- 24875135
TI  - Self-assembled nanostructures of amphiphilic zinc(II) salophen complexes: role of
      the solvent on their structure and morphology.
AB  - This contribution explores the effect of several solvent properties, such as
      volatility, polarity, and Lewis basicity on the formation of molecular self
      assembled nanostructures in the solid state, obtained either by casting of
      related solutions or by complete solvent evaporation, using seven solvents
      representative of common classes of coordinating organic solvents, of an
      amphiphilic Zn(II) Schiff-base complex. In all cases, the existence of well
      defined X-ray diffraction patterns, for both the cast and powder samples,
      indicates a strong tendency towards the molecular self-assembly of such
      complexes. While nanostructures formed in acetone, THF, pyridine, and DMF have a
      lamellar organization, those formed in ACN, ethanol, and DMSO exhibit a 2D
      columnar square structure. Field emission scanning electron microscopy analysis
      indicates that nanostructures formed in volatile acetone, THF, ACN, and ethanol
      solvents show a fibrous morphology, while those formed in less volatile pyridine,
      DMF, and DMSO have a ribbon appearance. Overall, the results indicate that while
      the formation of such nanostructures is independent of the Lewis basicity of the
      solvent, the solvent polarity affects their structure - more polar solvents
      favour higher symmetry structures - and the solvent volatility influences their
      morphology and ordering in the cast films - lower volatility of the solvent
      parallels the formation of much more ordered structures. Therefore, the
      appropriate choice of solvent allows control of the structure, morphology, and
      ordering of these molecular assemblies. 

PMID- 24875132
TI  - Inhibition of EGFR, HER2 and HER3 signaling with AZD8931 alone and in combination
      with paclitaxel: phase i study in Japanese patients with advanced solid
      malignancies and advanced breast cancer.
AB  - BACKGROUND: AZD8931 is an equipotent, reversible inhibitor of signaling by
      epidermal growth factor receptor (EGFR), human EGFR 2 (HER2) and HER3. This two
      part Japanese study (NCT01003158) assessed the safety/tolerability of AZD8931
      monotherapy in patients with advanced solid tumors and in combination with
      paclitaxel in female patients with advanced breast cancer. METHODS: Monotherapy
      part: ascending doses of AZD8931 (40/60/80 mg twice daily [bid]) for 21
      consecutive days. Combination part: AZD8931 40 mg bid and paclitaxel 90 mg/m(2)
      (on days 1, 8 and 15 of a 28-day cycle). RESULTS: Seventeen patients received
      AZD8931: 11 received AZD8931 monotherapy (40/60/80 mg [n = 3/4/4]) and six
      AZD8931 40 mg bid plus paclitaxel. No dose-limiting toxicities were observed for
      AZD8931 alone or combined with paclitaxel. The most frequent adverse events (AEs)
      were diarrhea, paronychia, pustular rash and dry skin (each n = 8) with AZD8931
      monotherapy and diarrhea, stomatitis, rash, alopecia, epistaxis and neutropenia
      (each n = 4) with combination therapy. Grade >=3 AEs were reported for one, two
      and four patients in the 40 mg, 60 mg and combination groups, respectively.
      AZD8931 was rapidly absorbed with a half-life of 12 h. There was no evidence of
      pharmacokinetic interaction between AZD8931 and paclitaxel. Two patients (one in
      each part) had unconfirmed and confirmed partial responses, with a duration of 42
      and 172 days, respectively. CONCLUSION: Although maximum tolerated dose was not
      confirmed for AZD8931, based on overall incidence of rash and diarrhea AEs in the
      80 mg group, doses up to 60 mg bid as monotherapy and 40 mg bid combined with
      paclitaxel are the feasible AZD8931 doses in Japanese patients.

PMID- 24875133
TI  - A phase I study of decitabine with pegylated interferon alpha-2b in advanced
      melanoma: impact on DNA methylation and lymphocyte populations.
AB  - BACKGROUND: Melanoma cell lines treated with decitabine show upregulation of
      cancer antigens, and interferon-alpha upregulates MHC Class I antigens in cancer
      cells, leading to enhanced T-cell recognition and T-cell mediated tumor
      apoptosis. We evaluated the synergy between the hypomethylating effects of
      decitabine and the immunomodulatory effects of interferon in a combination
      regimen administered to advanced melanoma patients in a phase 1 trial. METHODS:
      Patients with one prior systemic therapy were eligible. Using a modified 3 + 3
      design, patients received escalating doses of decitabine and pegylated interferon
      alpha-2b (PEG-IFN) during every 28-day treatment cycle. Global DNA methylation
      was measured on days 1 and 5 of cycles 1 and 3. Cytokine profiling and
      quantification of T-cell subpopulations by FACS were performed at baseline and
      cycle 3. RESULTS: Seventeen patients were assigned to one of four dose levels.
      Decitabine 15 mg/m2/d + PEG-IFN 3 MUg/kg was the maximum tolerated dose (MTD).
      Grade 3/4 cytopenias were seen across all dose levels: anemia (1), neutropenia
      (7), and thrombocytopenia (2). One patient remained progression-free for 37
      weeks. The other 16 patients progressed at or before 12 weeks. Median overall
      survival was 39 weeks. Hypomethylation was seen at all dose levels. Due to
      treatment-induced lymphocytopenia, absolute changes in T-cell populations post
      treatment were too small to be meaningfully interpreted. CONCLUSIONS: The
      response to this combination regimen was characterized by significant
      myelosuppression, particularly neutropenia. Although disappointing efficacy and
      slow accrual led to early closure of the trial, hypomethylation showed
      pharmacodynamic evidence of a therapeutic effect of decitabine at all dose
      levels.

PMID- 24875134
TI  - Pharmacokinetic/Pharmacodynamic modeling of abexinostat-induced thrombocytopenia
      across different patient populations: application for the determination of the
      maximum tolerated doses in both lymphoma and solid tumour patients.
AB  - BACKGROUND: In the clinical development of oncology drugs, the recommended dose
      is usually determined using a 3 + 3 dose-escalation study design. However, this
      phase I design does not always adequately describe dose-toxicity relationships.
      METHODS: 125 patients, with either solid tumours or lymphoma, were included in
      the study and 1217 platelet counts were available over three treatment cycles.
      The data was used to build a population pharmacokinetic/pharmacodynamic (PKPD)
      model using a sequential modeling approach. Model-derived Recommended Doses
      (MDRD) of abexinostat (a Histone Deacetylase Inhibitor) were determined from
      simulations of different administration schedules, and the higher bound for the
      probability of reaching these MDRD with a 3 + 3 design were obtained. RESULTS:
      The PKPD model developed adequately described platelet kinetics in both patient
      populations with the inclusion of two platelet baseline counts and a disease
      progression component for patients with lymphoma. Simulation results demonstrated
      that abexinostat administration during the first 4 days of each week in a 3-week
      cycle led to a higher MDRD compared to the other administration schedules tested,
      with a maximum probability of 40 % of reaching these MDRDs using a 3 + 3 design.
      CONCLUSIONS: The PKPD model was able to predict thrombocytopenia following
      abexinostat administration in both patient populations. A model-based approach to
      determine the recommended dose in phase I trials is preferable due to the
      imprecision of the 3 + 3 design.

PMID- 24875136
TI  - Concordance between RT-PCR-based detection of respiratory viruses from nasal
      swabs collected for viral testing and nasopharyngeal swabs collected for
      bacterial testing.
AB  - BACKGROUND: Epidemiologic studies of respiratory infections frequently rely on
      separate sample collections for the detection of bacteria and viruses. The
      requirement for two specimens presents cost, logistical, and acceptability
      challenges. OBJECTIVES: To determine the agreement in detection of respiratory
      viruses using RT-PCR between two different types of samples collected on the same
      day: nasal swabs preserved in viral transport medium (NS) and nasopharyngeal
      swabs preserved in skim milk-tryptone-glucose-glycerol [STGG] medium (NP), the
      current standard for pneumococcal colonization studies. STUDY DESIGN: Paired NS
      and NP samples were collected between May 2009 and September 2011 as part of the
      RESPIRA-PERU study, a large prospective cohort of Andean children <3 years of
      age. NS samples used polyester swabs and viral transport medium whereas NP
      samples used rayon wire-handled swabs and STGG medium. Samples were tested for
      influenza, human metapneumovirus (MPV), respiratory syncytial virus (RSV), human
      rhinovirus (HRV), parainfluenza virus 3 (PIV3) and adenovirus (ADV) using real
      time RT-PCR. We calculated the agreement, and compared cycle thresholds (CT)
      between NP and NS samples. RESULTS: Among 226 paired NP-NS samples, we observed
      very high agreement with a Kappa statistic ranging from 0.71 for ADV to 0.97 for
      MPV. CT values were similar for both strategies. CONCLUSIONS: NP samples
      preserved in STGG provide a simple and reliable strategy for identification of
      both pneumococcus and respiratory viruses. This single specimen collection
      strategy could be used for epidemiologic studies, especially in resource-limited
      settings. Furthermore, archived NP-STGG specimens from previous studies could be
      reliably tested by RT-PCR for viruses.

PMID- 24875137
TI  - Surveillance of group A Rotavirus in Buenos Aires 2008-2011, long lasting
      circulation of G2P[4] strains possibly linked to massive monovalent vaccination
      in the region.
AB  - BACKGROUND: Group A rotaviruses (RVA) are the most frequent single etiological
      agents of severe diarrhea in infants. Since 2006 RVA vaccines have been
      introduced in national schedules of middle and high income countries with
      substantial declines in rotavirus associated disease burden. However,
      surveillance must be maintained to, eventually, detect emerging types or variants
      selected by the new pressure imposed by vaccination. OBJECTIVES: To analyze the
      molecular epidemiology of group A rotavirus after vaccine introduction in the
      region in the context of data from more than 15 years of continuous surveillance
      in Buenos Aires. STUDY DESIGN: RVA positive diarrhea samples collected in Buenos
      Aires from 2008 to 2011 were genotyped by RT-PCR. Selected samples were sequenced
      to gain insight on evolution of common and globally emerging human RVA strains.
      RESULTS: Lineage III G12P[8] strain emerged in 2008 in Buenos Aires and shared co
      dominancy with G3 strains during 2009. An atypical long lasting circulation of
      G2P[4] strains since 2004 reached rates around 80% in 2011 in Buenos Aires.
      Sequencing of the VP7 and VP4 genes of representative G2P[4] isolates suggests
      Brazil as the origin of the 2010-2011 strains. CONCLUSIONS: Globally emergent G12
      lineage III strains could be established as dominant strains in a very populated
      area in two years since emergence. In this work it was also shown that the
      persistence of G2P[4] strains during 8 years could be related to massive
      immunization with the monovalent vaccine in the region.

PMID- 24875138
TI  - Laboratory testing of clinically approved drugs against Balamuthia mandrillaris.
AB  - Balamuthia mandrillaris is a free-living protist pathogen that can cause life
      threatening granulomatous amoebic encephalitis. Given the lack of effective
      available drugs against B. mandrillaris encephalitis with a mortality rate of
      more than 90%, here we screened drugs, targeting vital cellular receptors and
      biochemical pathways, that are already in approved clinical use for their
      potential clinical usefulness. Amoebicidal assays were performed by incubating B.
      mandrillaris with drugs (3 * 10(5) cells/0.5 mL/well) in phosphate buffered
      saline for 24 h and viability was determined using Trypan blue exclusion
      staining. For controls, amoebae were incubated with the solvent alone. To
      determine whether effects are reversible, B. mandrillaris were pre-exposed to
      drugs for 24 h, washed twice, and incubated with human brain microvascular
      endothelial cells, which constitute the blood-brain barrier as food source, for
      up to 48 h. Of the ten drugs tested, amlodipine, apomorphine, demethoxycurcumin,
      haloperidol, loperamide, prochlorperazine, procyclidine, and resveratrol showed
      potent amoebicidal effects, while amiodarone and digoxin exhibited minimal
      effectiveness. When pre-treated with these drugs, no viable trophozoites re
      emerged, suggesting that drugs destroyed parasite irreversibly. Based on the in
      vitro assay, amlodipine, apomorphine, demethoxycurcumin, haloperidol, loperamide,
      prochlorperazine, procyclidine, and resveratrol are potential antimicrobials for
      further testing against B. mandrillaris encephalitis. These findings may provide
      novel strategies for therapy but further research is needed to determine clinical
      usefulness of aforementioned drugs against granulomatous amoebic encephalitis
      caused by B. mandrillaris, and other free-living amoebae, such as Acanthamoeba
      spp., and Naegleria fowleri.

PMID- 24875139
TI  - Zeptomole detection of C-reactive protein in serum by a nanoparticle amplified
      surface plasmon resonance imaging aptasensor.
AB  - Diagnostic biomarkers (i.e. proteins) are often in low abundance in bodily fluids
      presenting many challenges for their detection. In order to extend the
      application of SPRi systems in detecting biomarkers at ultralow levels, we
      combine the advantage of aptamer technology with nanomaterials and microwave
      assisted surface functionalization. By implementing a sandwich assay through the
      introduction of aptamer-modified quantum dots (QDs), it was possible to measure 7
      zeptomole (at 5 fg/mL) of C-reactive protein (CRP) selectively in spiked human
      serum. It is expected that the proposed platform will provide new direction in
      designing ultrasensitive SPRi biosensors with multiplexing capabilities.

PMID- 24875141
TI  - Will ultrasound scanners replace the stethoscope?

PMID- 24875140
TI  - Soluble biglycan induces the production of ICAM-1 and MCP-1 in human aortic valve
      interstitial cells through TLR2/4 and the ERK1/2 pathway.
AB  - OBJECTIVE: Mononuclear cell infiltration in valvular tissue is one of the
      characteristics in calcific aortic valve disease. The inflammatory responses of
      aortic valve interstitial cells (AVICs) play an important role in valvular
      inflammation. However, it remains unclear what may evoke AVIC inflammatory
      responses. Accumulation of biglycan has been found in diseased aortic valve
      leaflets. Soluble biglycan can function as a danger-associated molecular pattern
      to induce the production of proinflammatory mediators in cultured macrophages. We
      tested the hypothesis that soluble biglycan induces AVIC production of
      proinflammatory mediators involved in mononuclear cell infiltration through Toll
      like receptor (TLR)-dependent signaling pathways. METHODS: Human AVICs isolated
      from normal aortic valve leaflets were treated with specific siRNA and
      neutralizing antibody against TLR2 or TLR4 before biglycan stimulation. The
      production of ICAM-1 and MCP-1 was assessed. To determine the signaling pathway
      involved, phosphorylation of ERK1/2 and p38 MAPK was analyzed, and specific
      inhibitors of ERK1/2 and p38 MAPK were applied. RESULTS: Soluble biglycan induced
      ICAM-1 expression and MCP-1 release in human AVICs, but had no effect on IL-6
      release. TLR4 blockade and knockdown reduced ICAM-1 and MCP-1 production induced
      by biglycan, while knockdown and neutralization of TLR2 resulted in greater
      suppression of the inflammatory responses. Biglycan induced the phosphorylation
      of ERK1/2 and p38 MAPK, but ICAM-1 and MCP-1 production was reduced only by
      inhibition of the ERK1/2 pathway. Further, inhibition of ERK1/2 attenuated NF
      kappaB activation following biglycan treatment. CONCLUSIONS: Soluble biglycan
      induces the expression of ICAM-1 and MCP-1 in human AVICs through TLR2 and TLR4
      and requires activation of the ERK1/2 pathway. AVIC inflammatory responses
      induced by soluble biglycan may contribute to the mechanism of chronic
      inflammation associated with calcific aortic valve disease.

PMID- 24875142
TI  - Long-term reproducibility of GABA magnetic resonance spectroscopy.
AB  - Recent findings suggest that cortical gamma aminobutyric acid (GABA) levels may
      provide a surrogate marker for a number of psychiatric and neurological
      conditions, as well as behavioural traits. However, the natural variability of
      GABA levels in the human brain over long periods of time (>8 days) has not yet
      been studied. The purpose of this work was to investigate the long-term
      variability of GABA concentrations in the human occipital cortex. Nineteen
      healthy male participants were recruited and underwent two sessions of magnetic
      resonance spectroscopy (MRS) to determine occipital GABA levels with an average
      between-session interval of 7 months. We assessed between-session variability, as
      well as the correlation between session 1 and session 2 GABA measurements. The
      mean coefficient of variation between sessions was 4.3% (bootstrap 95% confidence
      interval: 2.5, 6.4), which is comparable to reported GABA variability
      measurements over much shorter time intervals (<8 days). A significant positive
      correlation was observed between session 1 and session 2 GABA measurements
      (r=0.53, p=0.014), and the intra-class correlation coefficient was calculated to
      be 0.52 which was also statistically significant (p=0.012). These findings
      establish experimentally that GABA concentrations in the occipital cortex, as
      measured by MRS, are relatively stable over periods as long as 7 months. The
      findings have significant implications for the internal validity of longitudinal
      studies of GABA levels in the human brain, and they lend foundational support to
      studies relating GABA levels to behavioural traits in healthy individuals.

PMID- 24875143
TI  - Do tasks matter in task switching? Dissociating domain-general from context
      specific brain activity.
AB  - Throughout the past decade, the task-switching paradigm has been used extensively
      as a tool to delineate the neural mechanisms underlying flexible and goal
      directed action control. Yet, given a large number of experimental procedures,
      the task-switching literature has yielded considerable inconsistencies calling
      for a systematic evaluation of the impact of methodological parameters. In the
      present study, we examine a fundamental and implicit assumption that has guided
      previous research on task switching. Does switch-related brain activation (i.e.,
      the contrast between preparatory activity on switch versus repetition trials)
      reflect abstract cognitive control processes that are independent of specific
      task demands, and thus equivalent across different types of tasks? To answer this
      question, we compared the data of two fMRI studies that examined updating of task
      goals and/or stimulus-response mappings under almost identical protocols, but
      using entirely different tasks. In line with an abstract control process view,
      our results show that the vast majority of switch-related brain activity is
      insensitive to the context in which it occurs. The only region that exhibited a
      reliable contextual modulation was the anterior cingulate cortex, indicating that
      its contribution to preparatory adjustments might be linked to specific task
      demands. 

PMID- 24875144
TI  - Spatiotemporal dynamics of early cortical gesture processing.
AB  - Gesture processing has been consistently shown to be associated with activation
      of the inferior parietal lobe (IPL); however, little is known about the
      integration of IPL activation into the temporal dynamics of early sensory areas.
      Using a temporally graded repetition suppression paradigm, we examined the
      activation and time course of brain areas involved in hand gesture processing. We
      recorded event-related potentials in response to stimulus pairs of static hand
      images forming gestures of the popular rock-paper-scissors game and estimated
      their neuronal generators. We identified two main components associated with
      adaptive patterns related to stimulus repetition. The N190 component elicited at
      temporo-parietal sites adapted to repetitions of the same gesture and was
      associated with right-hemispheric extrastriate body area activation. A later
      component at parieto-occipital sites demonstrated temporally graded adaptation
      effects for all gestures with a left-hemispheric dominance. Source localization
      revealed concurrent activations of the right extrastriate body area, fusiform
      gyri bilaterally, and the left IPL at about 250 ms. The adaptation pattern
      derived from the graded repetition suppression paradigm demonstrates the
      functional sensitivity of these sources to gesture processing. Given the
      literature on IPL contribution to imitation, action recognition, and action
      execution, IPL activation at about 250 ms may represent the access into specific
      cognitive routes for gesture processing and may thus be involved in integrating
      sensory information from cortical body areas into subsequent visuo-motor
      transformation processes.

PMID- 24875145
TI  - Rutin inhibits UVB radiation-induced expression of COX-2 and iNOS in hairless
      mouse skin: p38 MAP kinase and JNK as potential targets.
AB  - Exposure to ultraviolet B (UVB) radiation, a complete environmental carcinogen,
      induces oxidative and inflammatory skin damage, thereby increasing the risk of
      skin carcinogenesis. The antioxidant and anti-inflammatory activities of a wide
      variety of plant polyphenols have been reported. Rutin (3-rhamnosyl
      glucosylquercetin), a polyphenol present in many edible plants, possesses diverse
      pharmacological properties including antioxidant, anti-inflammatory,
      antimutagenic and anticancer activities. The present study was aimed to
      investigate the effects of rutin on UVB-induced inflammation in mouse skin in
      vivo. Topical application of rutin onto the dorsal skin of female HR-1 hairless
      mice 30 min prior to UVB irradiation diminished epidermal hyperplasia and the
      levels of proteins modified by 4-hydroxynonenal, which is a biochemical hallmark
      of lipid peroxidation. Topical application of rutin also significantly inhibited
      UVB-induced expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide
      synthase (iNOS), two representative inflammatory enzymes, in hairless mouse skin.
      Rutin inhibited the DNA binding of activator protein-1 (AP-1) and phosphorylation
      of signal transducer and activator of transcription-3 (STAT3) in mouse skin
      exposed to UVB. Moreover, rutin attenuated UVB-induced phosphorylation of p38
      mitogen-activated protein (MAP) kinase and c-Jun-N-terminal kinase (JNK).
      Pharmacological inhibition of p38 MAP kinase and JNK decreased UVB-induced
      expression of COX-2 in mouse skin. Taken together, these findings suggest that
      rutin exerts anti-inflammatory effects in UVB-irradiated mouse skin by inhibiting
      expression of COX-2 and iNOS, which is attributable to its suppression of p38 MAP
      kinase and JNK signaling responsible for AP-1 activation.

PMID- 24875146
TI  - Regulation of cortical and trabecular bone mass by communication between
      osteoblasts, osteocytes and osteoclasts.
AB  - The size and strength of bone is determined by two fundamental processes. One
      process, bone remodelling, renews the skeleton throughout life. In this process
      existing bone is resorbed by osteoclasts and replaced, in the same location, by
      osteoblasts. The other process is bone modelling, where bone formation and
      resorption occur at different sites so that the shape of bone is changed. Recent
      data suggests that both remodelling and modelling are controlled by signals
      between the cells that carry out these two processes. Osteoclasts both resorb
      bone, and provide inhibitory and stimulatory signals, including cardiotrophin-1
      and sphingosine-1-kinase, to the osteoblast lineage thereby regulating their
      differentiation and activity on both trabecular and cortical surfaces. In
      addition, the osteoblast lineage, including osteoblast progenitors, matrix
      producing osteoblasts, bone lining cells, and matrix-embedded osteocytes, produce
      both inhibitory and stimulatory factors that stimulate osteoclast
      differentiation. We will discuss the roles of osteoblast- and osteocyte-derived
      RANKL, and paracrine, autocrine and endocrine factors, such as ephrinB2, the IL
      6/gp130 family of cytokines, parathyroid hormone, and its related peptide, PTHrP.
      These factors not only stimulate RANKL production, but also stimulate osteoblast
      differentiation and activity. This review will focus on recent data, generated
      from pharmacological and genetic studies of mouse models and what these data
      reveal about these pathways at different stages of osteoblast differentiation and
      their impact on both bone remodelling and modelling in trabecular and cortical
      bone. 

PMID- 24875147
TI  - Polyphenols and mitochondria: an update on their increasingly emerging ROS
      scavenging independent actions.
AB  - Polyphenols, ubiquitously present in fruits and vegetables, have been
      traditionally viewed as antioxidant molecules. Such contention emerged, mainly
      from their well established in vitro ability to scavenge free radicals and other
      reactive oxygen species (ROS). During the last decade, however, increasing
      evidence has emerged supporting the ability of certain polyphenols to also exert
      numerous ROS-scavenging independent actions. Although the latter can comprise the
      whole cell, particular attention has been placed on the ability of polyphenols to
      act, whether favorably or not, on a myriad of mitochondrial processes. Thus, some
      particular polyphenols are now recognized as molecules capable of modulating
      pathways that define mitochondrial biogenesis (i.e., inducing sirtuins),
      mitochondrial membrane potential (i.e., mitochondrial permeability transition
      pore opening and uncoupling effects), mitochondrial electron transport chain and
      ATP synthesis (i.e., modulating complexes I to V activity), intra-mitochondrial
      oxidative status (i.e., inhibiting/inducing ROS formation/removal enzymes), and
      ultimately mitochondrially-triggered cell death (i.e., modulating intrinsic
      apoptosis). The present review describes recent evidence on the ability of some
      polyphenols to modulate each of the formerly mentioned pathways, and discusses on
      how, by acting on such mitochondrial processes, polyphenols may afford protection
      against those mitochondrial damaging events that appear to be key in the cellular
      toxicity induced by various xenobiotics as well as that seen during the
      development of several ROS-related diseases. 

PMID- 24875148
TI  - Development and optimization of curcumin-loaded mannosylated chitosan
      nanoparticles using response surface methodology in the treatment of visceral
      leishmaniasis.
AB  - OBJECTIVE: The study aims at formulation and optimization of macrophage-targeted
      curcumin-loaded mannosylated chitosan nanoparticles (Cur-MCNPs) of curcumin (CUR)
      to improve its therapeutic potential in the treatment of visceral leishmaniasis
      (VL). METHODS: Response surface methodology (RSM) using central composite design
      was employed to study the effect of formulation factors on physicochemical
      dependent characteristics. Chitosan was coupled with d-mannose, by reductive
      amination, to prepare a mannosylated chitosan, a conjugate polymer and a
      subsequent formulation of Cur-MCNPs. Optimized formulation prepared using RSM was
      evaluated for in vitro release kinetics at physiological pH 7.4 and endosomal
      macrophage pH 4.5; in vivo pharmacokinetic profile and targeting potential were
      evaluated by fluorescence microscopy. RESULTS: Optimized Cur-MCNPs exhibited
      spherical and smooth surface with a mean particle size of 215 nm, polydispersity
      index of 0.381, zeta potential of + 24.37 mV and % entrapment efficiency of
      82.12%. The pharmacokinetic study of optimized Cur-MCNPs showed significant
      improvement in the value of mean resident time (39.38 h) compared to free CUR
      solution (0.30 h) (p < 0.05). In vivo uptake study indicated that endocytosis
      took place effectively within the macrophages of reticuloendothelial system.
      CONCLUSIONS: Thus, Cur-MCNPs could be considered as a promising delivery strategy
      towards active targeting of CUR to macrophages for the effective treatment of VL.

PMID- 24875150
TI  - Recent advances in dearomatization of heteroaromatic compounds.
AB  - Dearomatization reactions provide the most efficient method for the synthesis of
      spiro- or fused-ring systems from readily available compounds. This review
      summarizes the recent developments in dearomatization reactions of indoles,
      pyridines, quinolines, isoquinolines, and some other heteroaromatic compounds.
      The applications of these methods in total synthesis of natural products are also
      briefly introduced. 

PMID- 24875149
TI  - Allergen-specific IL-5 responses in early childhood predict asthma at age eight.
AB  - BACKGROUND: The pattern of development of allergen-specific T cell cytokine
      responses in early childhood and their relation to later disease is poorly
      understood. Here we describe longitudinal changes in allergen-stimulated T cell
      cytokine responses and their relation to asthma and allergic disease during the
      first 8 years of life. METHODS: Subjects with a family history of asthma, who
      were enrolled antenatally in the Childhood Asthma Prevention Study (public trials
      registration number ACTRN12605000042640), had skin prick tests, clinical
      evaluation for asthma and eczema, and in vitro assessment of T cell cytokine
      responses to HDM extract performed at ages 18 months (n = 281), 3 years (n =
      349), 5 years (n = 370) and 8 years (n = 275). We measured interleukin (IL-) 13
      at 3, 5 and 8 years, and IL-5, IL-10, and interferon-gamma (IFN-gamma), at 18
      months, 3, 5 and 8 years by ELISA. A cohort analysis was undertaken. Independent
      effects of cytokine responses at each age on the risk of asthma and allergic
      outcomes at age 8 years were estimated by multivariable logistic regression.
      RESULTS: HDM-specific IL-5 responses increased with age. HDM-specific IL-13 and
      IL-10 responses peaked at age 5 years. HDM-specific IL-5 responses at 3 years, 5
      years and 8 years were significantly associated with the presence of asthma and
      atopy at 8 years. IL-13 responses at 3 years, 5 years and 8 years were
      significantly associated with atopy at 8 years, but this association was not
      independent of the effect of IL-5. Other HDM-specific cytokine responses were not
      independently related to asthma or eczema at 8 years. CONCLUSION: HDM-specific IL
      5 responses at age 3 years or later are the best measure of T cell function for
      predicting asthma at age 8 years.

PMID- 24875151
TI  - Selective interactions of zein microspheres with different class of drugs: an in
      vitro and in silico analysis.
AB  - In this study, we have evaluated the interactions of zein microspheres with
      different class of drugs (hydrophobic, hydrophilic, and amphiphilic) using in
      vitro and in silico analysis. Zein microspheres loaded with aceclofenac,
      metformin, and promethazine has been developed by solvent evaporation technique
      and analyzed for its compatibility. The physical characterization depicted the
      proper encapsulation of hydrophobic drug in the microspheres. The in vitro
      release study revealed the sustaining ability of the microspheres in the
      following order: hydrophobic > hydrophilic > amphiphilic. In silico analysis also
      confirmed the better binding affinity and greater interactions of hydrophobic
      drug with zein. The above results revealed that zein is more suitable for
      hydrophobic drugs in the development of sustained drug delivery systems using
      solvent evaporation technique. The study therefore envisages a scope for
      identifying the most suitable polymer for a sustained drug delivery system in
      accordance with the nature of the drug. 

PMID- 24875152
TI  - Positive animal welfare states and reference standards for welfare assessment.
AB  - Developments in affective neuroscience and behavioural science during the last 10
      15 years have together made it increasingly apparent that sentient animals are
      potentially much more sensitive to their environmental and social circumstances
      than was previously thought to be the case. It therefore seems likely that both
      the range and magnitude of welfare trade-offs that occur when animals are managed
      for human purposes have been underestimated even when minimalistic but arguably
      well-intentioned attempts have been made to maintain high levels of welfare. In
      light of these neuroscience-supported behaviour-based insights, the present
      review considers the extent to which the use of currently available reference
      standards might draw attention to these previously neglected areas of concern. It
      is concluded that the natural living orientation cannot provide an all-embracing
      or definitive welfare benchmark because of its primary focus on behavioural
      freedom. However assessments of this type, supported by neuroscience insights
      into behavioural motivation, may now carry greater weight when used to identify
      management practices that should be avoided, discontinued or substantially
      modified. Using currently accepted baseline standards as welfare reference points
      may result in small changes being accorded greater significance than would be the
      case if they were compared with higher standards, and this could slow the
      progress towards better levels of welfare. On the other hand, using "what animals
      want" as a reference standard has the appeal of focusing on the specific
      resources or conditions the animals would choose themselves and can potentially
      improve their welfare more quickly than the approach of making small increments
      above baseline standards. It is concluded that the cautious use of these
      approaches in different combinations could lead to recommendations that would
      more effectively promote positive welfare states in hitherto neglected areas of
      concern.

PMID- 24875154
TI  - The new Editors of Surgical Oncology.

PMID- 24875153
TI  - Additive benefits of external focus and enhanced performance expectancy for motor
      learning.
AB  - The authors examined the individual and combined influences of 2 factors that
      have been shown to benefit motor learning: an external focus of attention and
      enhanced performance expectancies. Another purpose of this study was to gain
      further insight into the mechanisms underlying these variables. In a factorial
      design, participants learning a novel motor skill (i.e., throwing with the non
      dominant arm) were or were not given external focus instructions, and were or
      were not provided bogus positive social-comparative feedback to enhance their
      expectancies. This resulted in 4 groups: external focus, enhanced expectancy,
      external focus/enhanced expectancy and control. External focus instructions and
      enhanced expectancies had additive benefits for learning: the external
      focus/enhanced expectancy group demonstrated the greatest throwing accuracy on
      both retention and transfer tests, while the accuracy scores of the external
      focus and enhanced expectancy groups were lower, but higher than those of the
      control group. Furthermore, self-efficacy was increased by both external focus
      and enhanced expectancy, and predicted retention and transfer performance.
      Positive affect was heightened in the enhanced expectancy and external
      focus/enhanced expectancy groups after practice and predicted transfer
      performance. The findings suggest that the learning benefits of an external focus
      and enhanced expectancies mediate learning through partially different
      mechanisms.

PMID- 24875163
TI  - Bilateral congenital adrenal agenesis: a rare disease entity and not a result of
      poor autopsy technique.
AB  - Congenital adrenal agenesis is an extremely rare condition wherein the adrenal
      glands fail to develop. The absence of adrenal tissue results in the complete
      absence of hormones produced in the adrenal cortex (cortisol, aldosterone) and
      medulla (catecholamines), and is not compatible with postnatal life without
      artificial hormone replacement therapy. To date, 9 cases of adrenal agenesis have
      been reported, many of which are associated with additional congenital anomalies.
      Most cases were not detected on antenatal imaging and were detected incidentally
      at postmortem examination. We present a case of adrenal agenesis, detected
      incidentally at postmortem examination after termination of pregnancy for
      suspected fetal hydrops, and review the heterogeneous phenotype of this condition
      with associated abnormalities and molecular genetics. This case reinforces the
      role of the perinatal autopsy to investigate cause of perinatal mortality,
      allowing correlation of pathology with antenatal imaging findings and clinical
      details.

PMID- 24875165
TI  - Model-free causality analysis of cardiovascular variability detects the
      amelioration of autonomic control in Parkinson's disease patients undergoing
      mechanical stimulation.
AB  - We tested the hypothesis that causality analysis, applied to the spontaneous beat
      to-beat variability of heart period (HP) and systolic arterial pressure (SAP),
      can identify the improvement of autonomic control linked to plantar mechanical
      stimulation in patients with Parkinson's disease (PD). A causality index,
      measuring the strength of the association from SAP to HP variability, and derived
      according to the Granger paradigm (i.e. SAP causes HP if the inclusion of SAP
      into the set of signals utilized to describe cardiovascular interactions improves
      the prediction of HP series), was calculated using both linear model-based (MB)
      and nonlinear model-free (MF) approaches. Univariate HP and SAP variability
      indices in time and frequency domains, and bivariate descriptors of the HP-SAP
      variability interactions were computed as well. We studied ten PD patients (age
      range: 57-78 years; Hoehn-Yahr scale: 2-3; six males, four females) without
      orthostatic hypotension or symptoms of orthostatic intolerance and 'on-time'
      according to their habitual pharmacological treatment. PD patients underwent
      recordings at rest in a supine position and during a head-up tilt before, and 24
      h after, mechanical stimulation was applied to the plantar surface of both feet.
      The MF causality analysis indicated a greater involvement of baroreflex in
      regulating HP-SAP variability interactions after mechanical stimulation.
      Remarkably, MB causality and more traditional univariate or bivariate techniques
      could not detect changes in cardiovascular regulation after mechanical
      stimulation, thus stressing the importance of accounting for nonlinear dynamics
      in PD patients. Due to the higher statistical power of MF causality we suggest
      its exploitation to monitor the baroreflex control improvement in PD patients,
      and we encourage the clinical application of the Granger causality approach to
      evaluate the modification of the autonomic control in relation to the application
      of a pharmacological treatment, a rehabilitation procedure or external
      intervention. 

PMID- 24875166
TI  - Langerhans cell histiocytosis: differences and similarities in long-term outcome
      of paediatric and adult patients at a single institutional centre.
AB  - PURPOSE: This study determined the frequency of clinical features, reactivations,
      sequelae, mortality, and overall survival (OS) and compared paediatric with adult
      Langerhans cell histiocytosis (LCH) patients. MATERIALS AND METHODS: Ninety
      patients (60 paediatric and 30 adults) with LCH treated during 28 years were
      analysed retrospectively. RESULTS: Craniofacial lesion was the most frequent
      lesion at LCH presentation in children and adults. However, some differences were
      found. Orbital lesions were more frequent in paediatric than adult patients (P =
      0.001). There was a tendency for mandible lesions to be more common in adults
      than the paediatric group (P = 0.0710). Mucocutaneous lesions were observed in a
      higher proportion in adults compared to paediatric patients (P = 0.0395).
      Reactivation episodes (36.8 versus 62.5%) and deaths (10.7 versus 24.0%) occurred
      in lower proportions in paediatric than adult patients, respectively. The
      probability of OS in 10 years for both groups was similar (P = 0.137).
      CONCLUSION: The OS was similar in both groups despite clinical differences
      between paediatric and adult patients, and higher reactivation and death rates in
      adults.

PMID- 24875167
TI  - Psychiatric disorders in primary care.

PMID- 24875164
TI  - Transplanted terminally differentiated induced pluripotent stem cells are
      accepted by immune mechanisms similar to self-tolerance.
AB  - The exact nature of the immune response elicited by autologous-induced
      pluripotent stem cell (iPSC) progeny is still not well understood. Here we show
      in murine models that autologous iPSC-derived endothelial cells (iECs) elicit an
      immune response that resembles the one against a comparable somatic cell, the
      aortic endothelial cell (AEC). These cells exhibit long-term survival in vivo and
      prompt a tolerogenic immune response characterized by elevated IL-10 expression.
      In contrast, undifferentiated iPSCs elicit a very different immune response with
      high lymphocytic infiltration and elevated IFN-gamma, granzyme-B and perforin
      intragraft. Furthermore, the clonal structure of infiltrating T cells from iEC
      grafts is statistically indistinguishable from that of AECs, but is different
      from that of undifferentiated iPSC grafts. Taken together, our results indicate
      that the differentiation of iPSCs results in a loss of immunogenicity and leads
      to the induction of tolerance, despite expected antigen expression differences
      between iPSC-derived versus original somatic cells. 

PMID- 24875168
TI  - Diagnosing bipolar disorder: Defining thresholds and setting boundaries.

PMID- 24875169
TI  - Child abuse and the dynamics of silence.

PMID- 24875171
TI  - Executive attention impairment in adolescents with schizophrenia who have used
      cannabis.
AB  - OBJECTIVE: Repeated exposure to cannabis in nonpsychotic adolescents is
      associated with impairments in executive control of attention, similar to those
      observed in young adults with first-episode schizophrenia. To assess the impact
      of recurrent exposure to cannabis on cognitive function, this study characterized
      attention performance in both nonpsychotic adolescents and adolescents with early
      onset schizophrenia (EOS). METHOD: The Attention Network Test, a standard
      procedure that estimates the functional state of neural networks controlling the
      efficiency of three different attentional behaviors (alerting, orienting, and
      executive attention), was administered to four groups of participants: (1)
      adolescents with EOS and comorbid cannabis use disorder (EOS+CUD; n=18), (2)
      "Pure" schizophrenia (EOS; n=34), (3) "Pure" cannabis use disorder (CUD; n=29),
      and (4) Healthy controls (HC; n=53). Task performance was examined with a 2*2
      design (EOS+ versus EOS- and CUD+ versus CUD-) using multivariate analysis of
      covariance. Correlative analyses were conducted between executive attention
      performance and measures of surface area in the right anterior cingulate cortex.
      RESULTS: A significant EOS*CUD interaction was observed. In the executive
      attention network, adolescents with EOS+CUD showed reduced efficiency relative to
      adolescents with pure EOS, whereas no group differences were found between
      adolescents with pure CUD and HC. Less efficient executive attention was
      significantly associated with smaller surface area in the right caudal anterior
      cingulate cortex in EOS+CUD. CONCLUSIONS: These preliminary data suggest that the
      presence of CUD has a moderating effect on attentional performance in adolescents
      with schizophrenia compared to nonpsychotic adolescents. These deficits could
      have a role in difficulties with self-regulation and predisposition to substance
      misuse in this patient group. The anatomic substrate of this cognitive deficit
      may be related to surface area in the right caudal anterior cingulate cortex.

PMID- 24875172
TI  - The Lille Apathy Rating Scale (LARS): exploring its psychometric properties in
      schizophrenia.
AB  - BACKGROUND: Apathy in schizophrenia patients is linked to marked functional
      impairments and can be defined as a quantitative reduction of voluntary, goal
      directed behaviors. If there are now convincing arguments to consider apathy as a
      multidimensional psychopathological state (cognitive, emotional, and behavioral),
      there is a lack of validated and standardized instruments for detecting apathy
      and assessing its multidimensional aspects in schizophrenia. The Lille Apathy
      Rating Scale (LARS) is a semi-structured interview, yielding a global score and
      composite subscores for the different domains of apathy and has been validated in
      several different contexts but not in schizophrenia patients. OBJECTIVE: The aim
      of this study is to examine the psychometric properties of the LARS and identify
      the distinct components of apathy in a sample of schizophrenia patients. METHODS:
      One hundred-and-twelve schizophrenia patients were included and they completed
      the LARS, The Calgary Depression Scale in Schizophrenia, the Positive and the
      Negative Syndrome Scale and the Scale for the Assessment of Negative Symptoms.
      The patient group was compared to 51 healthy control subjects. RESULTS: Principal
      component analysis showed that the LARS proved a single construct which forms the
      root of an oblique factor structure reflecting four dimensions: novelty and
      social life, behavioral involvement, emotional involvement, and judgment skills.
      The main psychometric properties of the LARS were satisfactory. CONCLUSIONS: Our
      findings show that the LARS has satisfactory psychometric properties when used in
      a different setting than the original version. The LARS is a promising instrument
      to examine apathy in schizophrenia through a multidimensional framework.

PMID- 24875170
TI  - PAX6 regulates melanogenesis in the retinal pigmented epithelium through feed
      forward regulatory interactions with MITF.
AB  - During organogenesis, PAX6 is required for establishment of various progenitor
      subtypes within the central nervous system, eye and pancreas. PAX6 expression is
      maintained in a variety of cell types within each organ, although its role in
      each lineage and how it acquires cell-specific activity remain elusive. Herein,
      we aimed to determine the roles and the hierarchical organization of the PAX6
      dependent gene regulatory network during the differentiation of the retinal
      pigmented epithelium (RPE). Somatic mutagenesis of Pax6 in the differentiating
      RPE revealed that PAX6 functions in a feed-forward regulatory loop with MITF
      during onset of melanogenesis. PAX6 both controls the expression of an RPE
      isoform of Mitf and synergizes with MITF to activate expression of genes involved
      in pigment biogenesis. This study exemplifies how one kernel gene pivotal in
      organ formation accomplishes a lineage-specific role during terminal
      differentiation of a single lineage.

PMID- 24875173
TI  - Itch elicited by intradermal injection of serotonin, intracisternal injection of
      morphine, and their synergistic interactions in rats.
AB  - We used the cheek model of itch and pain in rats to determine the dose-response
      relationships for intradermal injection of serotonin and alpha methylserotonin on
      scratching behavior. We also determined the dose-related effects of
      intracisternally injected morphine on scratching, effects that were greatly
      reduced by administration of the opiate antagonist naloxone. We then examined the
      interactions of intradermal injection of serotonin and intracisternal injection
      of morphine on scratching and found that the two procedures act synergistically
      to increase itch. These results suggest that morphine applied to the CNS is
      capable of producing itch and greatly increasing itch originating in the skin
      (hyperknesis). 

PMID- 24875174
TI  - Lactoferrin from bovine colostrum regulates prolyl hydroxylase 2 activity and
      prevents prion protein-mediated neuronal cell damage via cellular prion protein.
AB  - Prion disorders are associated with the conversion of normal cellular prion
      protein (PrPc) to the abnormal scrapie isoform of prion protein (PrPsc). Recent
      studies have shown that expression of normal PrPc is regulated by hypoxia
      inducible factor-1 alpha (HIF-1alpha), and that lactoferrin increases full-length
      PrPc on the cell surface. Lactoferrin is an 80-kDa iron-binding glycoprotein with
      various biological activities, including iron-chelating ability. HIF-1alpha and
      the associated ubiquitin-proteasome pathway are regulated by HIF prolyl
      hydroxylases 2 (PHD2). We hypothesized that lactoferrin regulates PHD2 expression
      and enzymatic activity, and the PHD2 regulation promotes HIF-1alpha stability and
      prevention of neuronal cell death mediated by prion protein (PrP) residues (106
      126). Lactoferrin prevented PrP (106-126)-induced neurotoxicity by the induction
      of PrPc expression via promoting HIF-1alpha stability in neuronal cells. Our
      results demonstrated that lactoferrin prevented PrP (106-126)-induced
      neurotoxicity via the up-regulation of HIF-1alpha stability determined by PHD2
      expression and enzymatic activity. These findings suggest that possible therapies
      such as PHD2 inhibition, or promotion of lactoferrin secretion, may have clinical
      benefits in neurodegenerative diseases, including prion disease. 

PMID- 24875175
TI  - Glutamate neurons within the midbrain dopamine regions.
AB  - Midbrain dopamine systems play important roles in Parkinson's disease,
      schizophrenia, addiction, and depression. The participation of midbrain dopamine
      systems in diverse clinical contexts suggests these systems are highly complex.
      Midbrain dopamine regions contain at least three neuronal phenotypes:
      dopaminergic, GABAergic, and glutamatergic. Here, we review the locations,
      subtypes, and functions of glutamatergic neurons within midbrain dopamine
      regions. Vesicular glutamate transporter 2 (VGluT2) mRNA-expressing neurons are
      observed within each midbrain dopamine system. Within rat retrorubral field
      (RRF), large populations of VGluT2 neurons are observed throughout its
      anteroposterior extent. Within rat substantia nigra pars compacta (SNC), VGluT2
      neurons are observed centrally and caudally, and are most dense within the
      laterodorsal subdivision. RRF and SNC rat VGluT2 neurons lack tyrosine
      hydroxylase (TH), making them an entirely distinct population of neurons from
      dopaminergic neurons. The rat ventral tegmental area (VTA) contains the most
      heterogeneous populations of VGluT2 neurons. VGluT2 neurons are found in each VTA
      subnucleus but are most dense within the anterior midline subnuclei. Some
      subpopulations of rat VGluT2 neurons co-express TH or glutamic acid decarboxylase
      (GAD), but most of the VGluT2 neurons lack TH or GAD. Different subsets of rat
      VGluT2-TH neurons exist based on the presence or absence of vesicular monoamine
      transporter 2, dopamine transporter, or D2 dopamine receptor. Thus, the capacity
      by which VGluT2-TH neurons may release dopamine will differ based on their
      capacity to accumulate vesicular dopamine, uptake extracellular dopamine, or be
      autoregulated by dopamine. Rat VTA VGluT2 neurons exhibit intrinsic VTA
      projections and extrinsic projections to the accumbens and to the prefrontal
      cortex. Mouse VTA VGluT2 neurons project to accumbens shell, prefrontal cortex,
      ventral pallidum, amygdala, and lateral habenula. Given their molecular diversity
      and participation in circuits involved in addiction, we hypothesize that
      individual VGluT2 subpopulations of neurons play unique roles in addiction and
      other disorders. 

PMID- 24875177
TI  - Systemic inflammation alters satellite glial cell function and structure. A
      possible contribution to pain.
AB  - Local peripheral injury activates satellite glial cells (SGCs) in sensory
      ganglia, which may contribute to chronic pain. We hypothesized that systemic
      inflammation affects sensory ganglia like local injury. We induced systemic
      inflammation in mice by injecting lipopolysaccharide (LPS) intraperitoneally, and
      characterized SGCs and neurons in dorsal root ganglia (DRG), using dye injection,
      calcium imaging, electron microscopy (EM), immunohistochemistry, and electrical
      recordings. Several days post-LPS, SGCs were activated, and dye coupling among
      SGCs increased 3-4.5-fold. EM showed abnormal growth of SGC processes and the
      formation of new gap junctions. Sensitivity of SGCs to ATP increased twofold, and
      neuronal excitability was augmented. Blocking gap junctions reduced pain behavior
      in LPS-treated mice. Thus, changes in DRG due to systemic inflammation are
      similar to those due to local injury, which may explain the pain in sickness
      behavior and in other systemic diseases. 

PMID- 24875176
TI  - AMP kinase regulates K-ATP currents evoked by NMDA receptor stimulation in rat
      subthalamic nucleus neurons.
AB  - Our lab recently showed that N-methyl-D-aspartate (NMDA) evokes ATP-sensitive
      K(+) (K-ATP) currents in subthalamic nucleus (STN) neurons in slices of the rat
      brain. Both K-ATP channels and 5'-adenosine monophosphate-activated protein
      kinase (AMPK) are considered cellular energy sensors because their activities are
      influenced by the phosphorylation state of adenosine nucleotides. Moreover, AMPK
      has been shown to regulate K-ATP function in a variety of tissues including
      pancreas, cardiac myocytes, and hypothalamus. We used whole-cell patch clamp
      recordings to study the effect of AMPK activation on K-ATP channel function in
      STN neurons in slices of the rat brain. We found that bath or intracellular
      application of the AMPK activators A769662 and PT1 augmented tolbutamide
      sensitive K-ATP currents evoked by NMDA receptor stimulation. The effect of AMPK
      activators was blocked by the AMPK inhibitor dorsomorphin (compound C), and by
      STO609, an inhibitor of the upstream AMPK activator CaMKKbeta. AMPK augmentation
      of NMDA-induced K-ATP current was also blocked by intracellular BAPTA and by
      inhibitors of nitric oxide synthase and guanylyl cyclase. However, A769662 did
      not augment currents evoked by the K-ATP channel opener diazoxide. In the
      presence of NMDA, A769662 inhibited depolarizing plateau potentials and burst
      firing, both of which could be antagonized by tolbutamide or dorsomorphin. These
      studies show that AMPK augments NMDA-induced K-ATP currents by a Ca(2+)-dependent
      process that involves nitric oxide and cGMP. By augmenting K-ATP currents, AMPK
      activation would be expected to dampen the excitatory effect of glutamate
      mediated transmission in the STN.

PMID- 24875179
TI  - PTEN degradation after ischemic stroke: a double-edged sword.
AB  - Tumor suppressor phosphatase and tensin homolog (PTEN) is highly expressed in
      neurons and PTEN inhibition has been reported to be neuroprotective against
      ischemic stroke in experimental models. On the other hand, PTEN deletion has been
      shown to lead to cognitive impairment. In the current study, we examined the
      expression and functions of PTEN in an ischemic stroke rodent model. We found
      rapid S-nitrosylation and degradation of PTEN after cerebral ischemia/reperfusion
      injury. PTEN degradation leads to activation of Akt. PTEN partial deletion or
      PTEN inhibition increased the expression of GABAA receptor (GABAAR) gamma2
      subunit and enhanced GABAA receptor current. After cerebral ischemia, increased
      expression of GABAAR gamma2 subunit was observed in the ischemia region and the
      penumbra area. We also observed PTEN loss in astrocytes after cerebral ischemia.
      Astrocytic PTEN partial knockout increased astrocyte activation and exacerbated
      ischemic damage. We speculated that ischemic stroke induced neuronal PTEN
      degradation, hence enhanced GABAA receptor-medicated neuronal activity inhibition
      which could attenuate excitotoxicity and provide neuroprotection during the acute
      phase after stroke, while inhibiting long-term functional recovery and
      contributing to vascular cognitive impairment after stroke. On the other hand,
      ischemic stroke induced astrocytic PTEN loss and enhanced ischemic damage and
      astrogliosis. Taken together, our study indicates that ischemic stroke induces
      rapid PTEN degradation in both neurons and astrocytes which play both protective
      and detrimental action in a spatiotemporal- and cell-type-dependent manner. Our
      study provides critical insight for targeting PTEN signaling pathway for stroke
      treatment. 

PMID- 24875180
TI  - Twenty-four-hour ambulatory blood pressure in adult women with urinary tract
      infection in childhood.
AB  - OBJECTIVE: To study 24-h ambulatory blood pressure (BP) and development of
      hypertension over four decades in women with childhood urinary tract infection
      (UTI) associated with renal damage. METHODS: A population-based group of 111
      women was followed from their first UTI in childhood. The cohort was investigated
      at a median age of 27 years using standardized office BP measurement and was
      reinvestigated 15 years later with 24-h ambulatory BP monitoring (ABPM) and Tc
      dimercaptosuccinic acid scan for evaluation of renal damage. RESULTS: Eighty-six
      women with median age 41 years completed the reinvestigation. Hypertension
      occurred in 26 women, four of 28 (14%) without and 22 of 58 (38%) with renal
      damage (P = 0.04). The hypertension was diagnosed before entry in seven and in
      the study by ABPM in another 19 women. In 78 women, of which 50 had renal damage,
      the ABPMs were correlated to renal damage. There was significant difference
      between the groups without and with renal damage when mean 24-h systolic, mean
      daytime systolic and mean night-time SBP were compared (P = 0.03, P = 0.04, P =
      0.01, respectively). The results remained significant when the group with damage
      was divided into subgroups with increasing extent of damage: class 1, 2 and 3 (P
      = 0.01, P = 0.02, P = 0.008, respectively). CONCLUSION: Women with UTI-associated
      renal damage but well preserved function had significantly higher 24-h ambulatory
      BP and more often hypertension than comparable women without damage. This shows
      that women with UTI-associated renal damage are at increased risk of hypertension
      and should be considered for regular BP screening, preferably with 24-h ABPM.

PMID- 24875181
TI  - Evaluation of renal nerve morphological changes and norepinephrine levels
      following treatment with novel bipolar radiofrequency delivery systems in a
      porcine model.
AB  - OBJECTIVE: To evaluate the safety and effectiveness of different bipolar
      radiofrequency system algorithms in interrupting the renal sympathetic nerves and
      reducing renal norepinephrine in a healthy porcine model. METHODS: A porcine
      model (N = 46) was used to investigate renal norepinephrine levels and changes to
      renal artery tissues and nerves following percutaneous renal denervation with
      radiofrequency bipolar electrodes mounted on a balloon catheter. Parameters of
      the radiofrequency system (i.e. electrode length and energy delivery algorithm),
      and the effects of single and longitudinal treatments along the artery were
      studied with a 7-day model in which swine received unilateral radiofrequency
      treatments. Additional sets of animals were used to examine norepinephrine and
      histological changes 28 days following bilateral percutaneous radiofrequency
      treatment or surgical denervation; untreated swine were used for comparison of
      renal norepinephrine levels. RESULTS: Seven days postprocedure, norepinephrine
      concentrations decreased proportionally to electrode length, with 81, 60 and 38%
      reductions (vs. contralateral control) using 16, 4 and 2-mm electrodes,
      respectively. Applying a temperature-control algorithm with the 4-mm electrodes
      increased efficacy, with a mean 89.5% norepinephrine reduction following a 30-s
      treatment at 68 degrees C. Applying this treatment along the entire artery length
      affected more nerves vs. a single treatment, resulting in superior norepinephrine
      reduction 28 days following bilateral treatment. CONCLUSION: Percutaneous renal
      artery application of bipolar radiofrequency energy demonstrated safety and
      resulted in a significant renal norepinephrine content reduction and renal nerve
      injury compared with untreated controls in porcine models.

PMID- 24875182
TI  - Evidence of bird dropping masquerading by a spider to avoid predators.
AB  - Masquerading comes at various costs and benefits. The principal benefit being the
      avoidance of predators. The orb-web spider Cyclosa ginnaga has a silver body and
      adds a white discoid-shaped silk decoration to its web. The size, shape and
      colour of C. ginnaga's body resemble, when viewed by the human eye against its
      decoration, a bird dropping. We therefore hypothesized that their body
      colouration might combine with its web decoration to form a bird dropping
      masquerade to protect it from predators. We measured the spectral reflectance of:
      (i) the spider's body, (ii) the web decoration, and (iii) bird droppings, in the
      field against a natural background and found that the colour of the spider bodies
      and decorations were indistinguishable from each other and from bird droppings
      when viewed by hymentopteran predators. We monitored the predatory attacks on C.
      ginnaga when the spider's body and/or its decorations were blackened and found
      that predator attack probabilities were greater when only the decorations were
      blackened. Accordingly, we concluded that C. ginnaga's decoration and body
      colouration forms a bird dropping masquerade, which reduces its probability of
      predation. 

PMID- 24875178
TI  - Neurotrophins in the ventral tegmental area: Role in social stress, mood
      disorders and drug abuse.
AB  - This review discusses the impact of neurotrophins and other trophic factors,
      including fibroblast growth factor and glial cell line-derived neurotrophic
      factor, on mood disorders, weight regulation and drug abuse, with an emphasis on
      stress- and drug-induced changes in the ventral tegmental area (VTA).
      Neurotrophins, comprising nerve growth factor, brain-derived neurotrophic factor
      (BDNF), and neurotrophins 3 and 4/5 play important roles in neuronal plasticity
      and the development of different psychopathologies. In the VTA, most research has
      focused on the role of BDNF, because other neurotrophins are not found there in
      significant quantities. BDNF originating in the VTA provides trophic support to
      dopamine neurons. The diverse intracellular signaling pathways activated by BDNF
      may underlie precise physiological functions specific to the VTA. In general, VTA
      BDNF expression increases after psychostimulant exposures, and enhanced BDNF
      level in the VTA facilitates psychostimulant effects. The impact of VTA BDNF on
      the behavioral effects of psychostimulants relies primarily on its action within
      the mesocorticolimbic circuit. In the case of opiates, VTA BDNF expression and
      effects seem to be dependent on whether an animal is drug-naive or has a history
      of drug use, only the latter of which is related to dopamine mechanisms. Social
      defeat stress that is continuous in mice or intermittent in rats increases VTA
      BDNF expression, and is associated with depressive and social avoidance
      behaviors. Intermittent social defeat stress induces persistent VTA BDNF
      expression that triggers psychostimulant cross-sensitization. Understanding the
      cellular and molecular substrates of neurotrophin effects may lead to novel
      therapeutic approaches for the prevention and treatment of substance use and mood
      disorders. 

PMID- 24875184
TI  - A nurse-run clinic for patients with incidentally discovered small abdominal
      aortic aneurysms is feasible and cost-effective.
AB  - INTRODUCTION: Patients with incidentally discovered small abdominal aortic
      aneurysms (AAA) require assessment by a vascular surgery department for possible
      enrollment in a surveillance programme. Our unit implemented a vascular nurse-run
      AAA clinic in October 2010. The aim of this study was to assess the feasibility
      of a specialist nurse-run small AAA clinic. METHODS: Demographic and clinical
      data were collected prospectively for all patients seen in the new vascular nurse
      clinic between October 2010 and November 2012. A validated AAA operative
      mortality score was used to aid decision making by the vascular nurse. RESULTS:
      Some 250 patients were seen in the clinic. 198 (79.2%) patients were enrolled in
      surveillance, 40 (16%) declined enrollment and 12 (4.8%) were referred to a
      consultant clinic for further assessment. The majority of patients were male and
      the mean age was 73.7 years. Co-morbidities included hypertension, a history of
      cardiovascular disease, and hyperlipidaemia. The majority of referrals were
      considered to be low operative risk. No aneurysms ruptured whilst under
      surveillance. CONCLUSIONS: A nurse-run clinic that assesses patients with
      incidentally discovered small AAAs for inclusion in AAA surveillance is a
      feasible alternative to assessment of these patients in a consultant-run clinic.

PMID- 24875183
TI  - SIRT1 mediates FOXA2 breakdown by deacetylation in a nutrient-dependent manner.
AB  - The Forkhead transcription factor FOXA2 plays a fundamental role in controlling
      metabolic homeostasis in the liver during fasting. The precise molecular
      regulation of FOXA2 in response to nutrients is not fully understood. Here, we
      studied whether FOXA2 could be controlled at a post-translational level by
      acetylation. By means of LC-MS/MS analyses, we identified five acetylated
      residues in FOXA2. Sirtuin family member SIRT1 was found to interact with and
      deacetylate FOXA2, the latter process being dependent on the NAD+-binding
      catalytic site of SIRT1. Deacetylation by SIRT1 reduced protein stability of
      FOXA2 by targeting it towards proteasomal degradation, and inhibited
      transcription from the FOXA2-driven G6pase and CPT1a promoters. While mutation of
      the five identified acetylated residues weakly affected protein acetylation and
      stability, mutation of at least seven additional lysine residues was required to
      abolish acetylation and reduce protein levels of FOXA2. The importance of
      acetylation of FOXA2 became apparent upon changes in nutrient levels. The
      interaction of FOXA2 and SIRT1 was strongly reduced upon nutrient withdrawal in
      cell culture, while enhanced Foxa2 acetylation levels were observed in murine
      liver in vivo after starvation for 36 hours. Collectively, this study
      demonstrates that SIRT1 controls the acetylation level of FOXA2 in a nutrient
      dependent manner and in times of nutrient shortage the interaction between SIRT1
      and FOXA2 is reduced. As a result, FOXA2 is protected from degradation by
      enhanced acetylation, hence enabling the FOXA2 transcriptional program to be
      executed to maintain metabolic homeostasis. 

PMID- 24875185
TI  - Carotid endarterectomy under local and/or regional anesthesia has less risk of
      myocardial infarction compared to general anesthesia: An analysis of national
      surgical quality improvement program database.
AB  - Multiple studies have evaluated the effect of anesthesia type on carotid
      endarterectomy with inconsistent results. Our study compared 30-day postoperative
      myocardial infarction, stroke, and mortality between carotid endarterectomy under
      local or regional anesthesia and carotid endarterectomy under general anesthesia
      utilizing National Surgical Quality Improvement Program database. All patients
      listed in National Surgical Quality Improvement Program database that underwent
      carotid endarterectomy under general anesthesia and local or regional anesthesia
      from 2005 to 2011 were included with the exception of patients undergoing
      simultaneous carotid endarterectomy and coronary artery bypass grafting. The data
      revealed substantial differences between the two groups compared, and these were
      adjusted using multiple logistic regression. Postoperative myocardial infarction,
      stroke, and death at 30 days were compared between the two groups. A total of
      42,265 carotid endarterectomy cases were included. A total of 37,502 (88.7%) were
      performed under general anesthesia and 4763 (11.3%) under local or regional
      anesthesia. Carotid endarterectomy under local or regional anesthesia had a
      significantly decreased risk of 30-day postoperative myocardial infarction when
      compared to carotid endarterectomy under general anesthesia (0.4% vs 0.86%, p =
      0.012). No statistically significant differences were found in postoperative
      stroke or mortality. Carotid endarterectomy under local or regional anesthesia
      carries a decreased risk of postoperative myocardial infarction when compared to
      carotid endarterectomy under general anesthesia. Therefore, patients at risk of
      postoperative myocardial infarction undergoing carotid endarterectomy,
      consideration of local or regional anesthesia may reduce that risk.

PMID- 24875186
TI  - Scabies mites alter the skin microbiome and promote growth of opportunistic
      pathogens in a porcine model.
AB  - BACKGROUND: The resident skin microbiota plays an important role in restricting
      pathogenic bacteria, thereby protecting the host. Scabies mites (Sarcoptes
      scabiei) are thought to promote bacterial infections by breaching the skin
      barrier and excreting molecules that inhibit host innate immune responses.
      Epidemiological studies in humans confirm increased incidence of impetigo,
      generally caused by Staphylococcus aureus and Streptococcus pyogenes, secondary
      to the epidermal infestation with the parasitic mite. It is therefore possible
      that mite infestation could alter the healthy skin microbiota making way for the
      opportunistic pathogens. A longitudinal study to test this hypothesis in humans
      is near impossible due to ethical reasons. In a porcine model we generated
      scabies infestations closely resembling the disease manifestation in humans and
      investigated the scabies associated changes in the skin microbiota over the
      course of a mite infestation. METHODOLOGY/PRINCIPAL FINDINGS: In a 21 week trial,
      skin scrapings were collected from pigs infected with S. scabies var. suis and
      scabies-free control animals. A total of 96 skin scrapings were collected before,
      during infection and after acaricide treatment, and analyzed by bacterial 16S
      rDNA tag-encoded FLX-titanium amplicon pyrosequencing. We found significant
      changes in the epidermal microbiota, in particular a dramatic increase in
      Staphylococcus correlating with the onset of mite infestation in animals
      challenged with scabies mites. This increase persisted beyond treatment from mite
      infection and healing of skin. Furthermore, the staphylococci population shifted
      from the commensal S. hominis on the healthy skin prior to scabies mite challenge
      to S. chromogenes, which is increasingly recognized as being pathogenic,
      coinciding with scabies infection in pigs. In contrast, all animals in the
      scabies-free cohort remained relatively free of Staphylococcus throughout the
      trial. CONCLUSIONS/SIGNIFICANCE: This is the first experimental in vivo evidence
      supporting previous assumptions that establishment of pathogens follow scabies
      infection. Our findings provide an explanation for a biologically important
      aspect of the disease pathogenesis. The methods developed from this pig trial
      will serve as a guide to analyze human clinical samples. Studies building on this
      will offer implications for development of novel intervention strategies against
      the mites and the secondary infections.

PMID- 24875187
TI  - Genome-wide estimation of linkage disequilibrium from population-level high
      throughput sequencing data.
AB  - Rapidly improving sequencing technologies provide unprecedented opportunities for
      analyzing genome-wide patterns of polymorphisms. In particular, they have great
      potential for linkage-disequilibrium analyses on both global and local genetic
      scales, which will substantially improve our ability to derive evolutionary
      inferences. However, there are some difficulties with analyzing high-throughput
      sequencing data, including high error rates associated with base reads and
      complications from the random sampling of sequenced chromosomes in diploid
      organisms. To overcome these difficulties, we developed a maximum-likelihood
      estimator of linkage disequilibrium for use with error-prone sampling data.
      Computer simulations indicate that the estimator is nearly unbiased with a
      sampling variance at high coverage asymptotically approaching the value expected
      when all relevant information is accurately estimated. The estimator does not
      require phasing of haplotypes and enables the estimation of linkage
      disequilibrium even when all individual reads cover just single polymorphic
      sites. 

PMID- 24875189
TI  - Detection, epidemiology and characterization of VP6 and VP7 genes of group D
      rotavirus in broiler chickens.
AB  - Rotaviruses infect humans and animals and are classified into eight groups (A to
      H). Group D rotavirus (RVD) has been described in birds, although relatively few
      reports are available. The present study focused on RVD, including
      epidemiological and molecular aspects of samples collected from broiler chickens
      in the state of Para, Brazil. A total of 85 faecal samples were collected between
      2008 and 2011 from 37 chicken farms located in eight different municipalities.
      The viral double-stranded RNA was extracted from faecal suspensions and analysed
      using polyacrylamide gel electrophoresis (PAGE), followed by reverse
      transcriptase-polymerase chain reaction (RT-PCR) and nucleotide sequencing of the
      VP6 and VP7 genes. Comparing the positive results, 16.5% (14/85) were obtained by
      PAGE and 35.3% (30/85) by RT-PCR. Samples from seven of eight municipalities were
      positive for RVD and infections were recorded in 17 (45.9%) of 37 chicken farms.
      The RVD infection rate was significantly higher in the 16-day to 30-day age group
      (62.2%; 23/37) compared with other ages. No consistent relationship was found
      between the infection rate and either the population density in poultry houses or
      the climatic conditions. The nucleotide sequences of the VP6 gene were 89.9 to
      90.9% similar to the prototype strain 05V0049 and were 88.3 to 100% similar among
      themselves; VP7 gene nucleotide sequences were 84.3 to 85.4% similar to the
      prototype strain 05V0049 and 93.8 to 100% similar among themselves. Overall, this
      study provides new insights into the epidemiology and genome characterization of
      group D rotaviruses. 

PMID- 24875190
TI  - The role of laboratory dissection training in neurosurgical residency: results of
      a national survey.
AB  - OBJECTIVE: Work hour restrictions and current quality, financial, and legal
      concerns have reduced resident operative volume and autonomy. Although laboratory
      (cadaveric or animal) dissection has a rich history in neurosurgery, its current
      role in resident training is unclear. Recent literature suggests educators have
      looked to simulation to accelerate the learning curve of acquiring neurosurgical
      technical skills. The purpose of this study was to determine the prevalence,
      characteristics, and extent of laboratory dissection in neurosurgical residency
      programs in the United States. METHODS: A survey was sent to program directors of
      all 100 neurosurgical residency programs in the United States. RESULTS: Response
      rate was 65%. Most programs (93.8%) incorporate laboratory dissection into
      resident training. Most programs have 1-3 (36.1%) or 4-6 (39.3%) sessions
      annually. Residents in postgraduate years 2-6 (85.2%-93.4%) most commonly
      participate. The most common topics are cranial approaches (100%), spinal
      approaches (88.5%), spine instrumentation (80.3%), and endoscopy (50.8%). Thirty
      one (47.7%) programs use artificial physical model or virtual reality simulators;
      the most common simulators are endoscopy (15.4%), microvascular anastomosis
      (13.8%), and endovascular (10.8%). Only 8 programs (13.1%) formally grade
      dissection skills. Educators (95.4%) believe laboratory dissection is an integral
      component of training and no respondent believed simulation could currently
      provide greater educational benefit than laboratory dissection. Most (89.2%)
      respondents would support a national "suggested" dissection curriculum and
      manual. CONCLUSIONS: In neurosurgical resident education, laboratory dissection
      is widely used; however, significant variation exists. Nonetheless, program
      directors believe laboratory dissection plays an integral role in neurosurgical
      training and is currently associated with greater educational benefit than
      simulation.

PMID- 24875188
TI  - The role of Dbf4-dependent protein kinase in DNA polymerase zeta-dependent
      mutagenesis in Saccharomyces cerevisiae.
AB  - The yeast Dbf4-dependent kinase (DDK) (composed of Dbf4 and Cdc7 subunits) is an
      essential, conserved Ser/Thr protein kinase that regulates multiple processes in
      the cell, including DNA replication, recombination and induced mutagenesis. Only
      DDK substrates important for replication and recombination have been identified.
      Consequently, the mechanism by which DDK regulates mutagenesis is unknown. The
      yeast mcm5-bob1 mutation that bypasses DDK's essential role in DNA replication
      was used here to examine whether loss of DDK affects spontaneous as well as
      induced mutagenesis. Using the sensitive lys2DeltaA746 frameshift reversion
      assay, we show DDK is required to generate "complex" spontaneous mutations, which
      are a hallmark of the Polzeta translesion synthesis DNA polymerase. DDK co
      immunoprecipitated with the Rev7 regulatory, but not with the Rev3 polymerase
      subunit of Polzeta. Conversely, Rev7 bound mainly to the Cdc7 kinase subunit and
      not to Dbf4. The Rev7 subunit of Polzeta may be regulated by DDK phosphorylation
      as immunoprecipitates of yeast Cdc7 and also recombinant Xenopus DDK
      phosphorylated GST-Rev7 in vitro. In addition to promoting Polzeta-dependent
      mutagenesis, DDK was also important for generating Polzeta-independent large
      deletions that revert the lys2DeltaA746 allele. The decrease in large deletions
      observed in the absence of DDK likely results from an increase in the rate of
      replication fork restart after an encounter with spontaneous DNA damage. Finally,
      nonepistatic, additive/synergistic UV sensitivity was observed in cdc7Delta
      pol32Delta and cdc7Delta pol30-K127R,K164R double mutants, suggesting that DDK
      may regulate Rev7 protein during postreplication "gap filling" rather than during
      "polymerase switching" by ubiquitinated and sumoylated modified Pol30 (PCNA) and
      Pol32. 

PMID- 24875191
TI  - American Society of Nephrology Quiz and Questionnaire 2013: RRT.
AB  - The Nephrology Quiz and Questionnaire (NQ&Q) remains an extremely popular session
      for attendees of the Annual Meeting of the American Society of Nephrology. As in
      past years, the conference hall of the 2013 meeting was overflowing with
      interested audience members. Topics covered by expert discussants included
      electrolyte and acid-base disorders, glomerular disease, ESRD/dialysis, and
      transplantation. Complex cases representing each of these categories, along with
      single best answer questions, were prepared by a panel of experts. Before the
      meeting, program directors of United States nephrology training programs answered
      questions through an Internet-based questionnaire. A new addition to the NQ&Q was
      participation in the questionnaire by nephrology fellows. To review the process,
      members of the audience test their knowledge and judgment on a series of case
      oriented questions prepared and discussed by experts. Their answers are compared
      in real time using audience response devices with the answers of nephrology
      fellows and training program directors. The correct and incorrect answers are
      then briefly discussed after the audience responses and the results of the
      questionnaire are displayed. This article recapitulates the session and
      reproduces its educational value for CJASN readers. Enjoy the clinical cases and
      expert discussions. 

PMID- 24875193
TI  - Skin autofluorescence and all-cause mortality in stage 3 CKD.
AB  - BACKGROUND AND OBJECTIVES: Novel markers may help to improve risk prediction in
      CKD. One potential candidate is tissue advanced glycation end product
      accumulation, a marker of cumulative metabolic stress, which can be assessed by a
      simple noninvasive measurement of skin autofluorescence. Skin autofluorescence
      correlates with higher risk of cardiovascular events and mortality in people with
      diabetes or people requiring RRT, but its role in earlier CKD has not been
      studied. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A prospective cohort of
      1741 people with CKD stage 3 was recruited from primary care between August 2008
      and March 2010. Participants underwent medical history, clinical assessment,
      blood and urine sampling for biochemistry, and measurement of skin
      autofluorescence. Kaplan-Meier plots and multivariate Cox proportional hazards
      models were used to investigate associations between skin autofluorescence
      (categorical in quartiles) and all-cause mortality. RESULTS: In total, 1707
      participants had skin autofluorescence measured; 170 (10%) participants died
      after a median of 3.6 years of follow-up. The most common cause of death was
      cardiovascular disease (41%). Higher skin autofluorescence was associated
      significantly with poorer survival (all-cause mortality, P<0.001) on Kaplan-Meier
      analysis. Univariate and age/sex-adjusted Cox proportional hazards models showed
      that the highest quartile of skin autofluorescence was associated with all-cause
      mortality (hazard ratio, 2.64; 95% confidence interval, 1.71 to 4.08; P<0.001 and
      hazard ratio, 1.84; 95% confidence interval, 1.18 to 2.86; P=0.003, respectively,
      compared with the lowest quartile). This association was not maintained after
      additional adjustment to include cardiovascular disease, diabetes, smoking, body
      mass index, eGFR, albuminuria, and hemoglobin. CONCLUSIONS: Skin autofluorescence
      was not independently associated with all-cause mortality in this study.
      Additional research is needed to clarify whether it has a role in risk prediction
      in CKD.

PMID- 24875194
TI  - A randomized, open-label, dose-response study of losartan in hypertensive
      children.
AB  - BACKGROUND AND OBJECTIVES: Once-daily losartan reduces BP in a dose-dependent
      manner and is well tolerated in hypertensive children aged 6-16 years. This study
      assessed the dose-response relationship, safety, and tolerability of losartan in
      hypertensive children aged 6 months to 6 years. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: This was a 12-week, randomized, open-label, dose-ranging study,
      with a 2-year extension. Patients were randomized to losartan at the following
      dosages: 0.1 mg/kg per day (low), 0.3 mg/kg per day (medium), or 0.7 mg/kg per
      day (high). Losartan was titrated to the next dose level (to a 1.4 mg/kg per day
      maximum dosage, not exceeding 100 mg/d, which was not one of the three original
      doses offered at randomization) at weeks 3, 6, and 9 for patients who did not
      attain their goal BP and were not taking the highest dose. Dose response was
      evaluated by analyzing the slope of change in sitting systolic BP (SBP; primary
      end point) and diastolic BP (DBP; secondary end point) after 3 weeks compared
      with baseline. Adverse events (AEs) were recorded throughout. RESULTS: Of the 101
      patients randomized, 99 were included in the analysis (low dose, n=32; medium
      dose, n=34; and high dose, n=33). Mean sitting BP decreased from baseline in the
      low-, medium-, and high-dose groups by 7.3, 7.6, and 6.7 mmHg, respectively, for
      SBP and 8.2, 5.1, and 6.7 mmHg, respectively, for DBP after 3 weeks. No dose
      response relationship was established by the slope analysis on SBP (P=0.75) or
      DBP (P=0.64). The BP-lowering effect was observed throughout the 2-year
      extension. The incidence of AEs was low and comparable between groups.
      CONCLUSIONS: Hypertensive children aged 6 months to 6 years treated with losartan
      0.1-0.7 mg/kg per day had clinically significant decreases from baseline in SBP
      and DBP, yet no dose-response relationship was evident. Losartan, at a dosage up
      to 1.4 mg/kg per day, was well tolerated.

PMID- 24875192
TI  - Collecting duct principal cell transport processes and their regulation.
AB  - The principal cell of the kidney collecting duct is one of the most highly
      regulated epithelial cell types in vertebrates. The effects of hormonal,
      autocrine, and paracrine factors to regulate principal cell transport processes
      are central to the maintenance of fluid and electrolyte balance in the face of
      wide variations in food and water intake. In marked contrast with the epithelial
      cells lining the proximal tubule, the collecting duct is electrically tight, and
      ion and osmotic gradients can be very high. The central role of principal cells
      in salt and water transport is reflected by their defining transporters-the
      epithelial Na(+) channel (ENaC), the renal outer medullary K(+) channel, and the
      aquaporin 2 (AQP2) water channel. The coordinated regulation of ENaC by
      aldosterone, and AQP2 by arginine vasopressin (AVP) in principal cells is
      essential for the control of plasma Na(+) and K(+) concentrations, extracellular
      fluid volume, and BP. In addition to these essential hormones, additional
      neuronal, physical, and chemical factors influence Na(+), K(+), and water
      homeostasis. Notably, a variety of secreted paracrine and autocrine agents such
      as bradykinin, ATP, endothelin, nitric oxide, and prostaglandin E2 counterbalance
      and limit the natriferic effects of aldosterone and the water-retaining effects
      of AVP. Considerable recent progress has improved our understanding of the
      transporters, receptors, second messengers, and signaling events that mediate
      principal cell responses to changing environments in health and disease. This
      review primarily addresses the structure and function of the key transporters and
      the complex interplay of regulatory factors that modulate principal cell ion and
      water transport. 

PMID- 24875197
TI  - The importance of briefings and debriefings.

PMID- 24875195
TI  - Acute respiratory distress syndrome and risk of AKI among critically ill
      patients.
AB  - BACKGROUND AND OBJECTIVES: Increasing experimental evidence suggests that acute
      respiratory distress syndrome (ARDS) may promote AKI. The primary objective of
      this study was to assess ARDS as a risk factor for AKI in critically ill
      patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was an
      observational study on a prospective database fed by 18 intensive care units
      (ICUs). Patients with ICU stays >24 hours were enrolled over a 14-year period.
      ARDS was defined using the Berlin criteria and AKI was defined using the Risk,
      Injury, Failure, Loss of kidney function, and End-stage kidney disease criteria.
      Patients with AKI before ARDS onset were excluded. RESULTS: This study enrolled
      8029 patients, including 1879 patients with ARDS. AKI occurred in 31.3% of
      patients and was more common in patients with ARDS (44.3% versus 27.4% in
      patients without ARDS; P<0.001). After adjustment for confounders, both
      mechanical ventilation without ARDS (odds ratio [OR], 4.34; 95% confidence
      interval [95% CI], 3.71 to 5.10) and ARDS (OR, 11.01; 95% CI, 6.83 to 17.73) were
      independently associated with AKI. Hospital mortality was 14.2% (n=1140) and was
      higher in patients with ARDS (27.9% versus 10.0% in patients without ARDS;
      P<0.001) and in patients with AKI (27.6% versus 8.1% in those without AKI;
      P<0.001). AKI was associated with higher mortality in patients with ARDS (42.3%
      versus 20.2%; P<0.001). CONCLUSIONS: ARDS was independently associated with AKI.
      This study suggests that ARDS should be considered as a risk factor for AKI in
      critically ill patients.

PMID- 24875196
TI  - The glomerulus: the sphere of influence.
AB  - The glomerulus, the filtering unit of the kidney, is a unique bundle of
      capillaries lined by delicate fenestrated endothelia, a complex mesh of proteins
      that serve as the glomerular basement membrane and specialized visceral
      epithelial cells that form the slit diaphragms between interdigitating foot
      processes. Taken together, this arrangement allows continuous filtration of the
      plasma volume. The dynamic physical forces that determine the single nephron
      glomerular filtration are considered. In addition, new insights into the cellular
      and molecular components of the glomerular tuft and their contribution to
      glomerular disorders are explored. 

PMID- 24875198
TI  - The future of nursing: an opportunity for advocacy.

PMID- 24875199
TI  - NPO practices and preoperative oral carbohydrate intake.

PMID- 24875200
TI  - Author response.

PMID- 24875201
TI  - Missed opportunity related to statistical methods.

PMID- 24875204
TI  - AORN surgical conference & expo education sessions.

PMID- 24875202
TI  - Author response.

PMID- 24875205
TI  - AORN surgical conference & expo general sessions.

PMID- 24875206
TI  - AORN surgical conference & expo business sessions.

PMID- 24875207
TI  - Research, evidence-based practice, and clinical improvement/innovation posters.

PMID- 24875209
TI  - Using an age-specific nursing model to tailor care to the adolescent surgical
      patient.
AB  - A surgical experience can be stressful for any patient. When the patient is an
      adolescent, however, the surgical experience can create significant stress, which
      is related to normal adolescent development. Perioperative nursing care should
      address what adolescent patients perceive as stressful and should provide a safe
      environment so that a successful surgical outcome can be achieved. To accomplish
      this, a nursing model specific to perioperative nursing practice should be
      developed to guide nurses when providing care to adolescents. The Adolescent
      Perioperative System Stability Model based on the Neuman Systems Model provides a
      framework for defining scope of practice and organizing nursing care that is
      appropriate for the adolescent during a surgical experience. In addition to
      guiding nursing practice, this model provides direction and guidance for future
      studies of adolescents in the perioperative setting. 

PMID- 24875210
TI  - Electromagnetic navigational bronchoscopy and robotic-assisted thoracic surgery.
AB  - With the use of electromagnetic navigational bronchoscopy and robotics, lung
      lesions can be diagnosed and resected during one surgical procedure. Global
      positioning system technology allows surgeons to identify and mark a thoracic
      tumor, and then robotics technology allows them to perform minimally invasive
      resection and cancer staging procedures. Nurses on the perioperative robotics
      team must consider the logistics of providing safe and competent care when
      performing combined procedures during one surgical encounter. Instrumentation, OR
      organization and room setup, and patient positioning are important factors to
      consider to complete the procedure systematically and efficiently. This
      revolutionary concept of combining navigational bronchoscopy with robotics
      requires a team of dedicated nurses to facilitate the sequence of events
      essential for providing optimal patient outcomes in highly advanced surgical
      procedures. 

PMID- 24875211
TI  - Applications for radio-frequency identification technology in the perioperative
      setting.
AB  - We implemented a two-year project to develop a security-gated management system
      for the perioperative setting using radio-frequency identification (RFID)
      technology to enhance the management efficiency of the OR. We installed RFID
      readers beside the entrances to the OR and changing areas to receive and process
      signals from the RFID tags that we sewed into surgical scrub attire and shoes.
      The system also required integrating automatic access control panels,
      computerized lockers, light-emitting diode (LED) information screens, wireless
      networks, and an information system. By doing this, we are able to control the
      flow of personnel and materials more effectively, reduce OR costs, optimize the
      registration and attire-changing process for personnel, and improve management
      efficiency. We also anticipate this system will improve patient safety by
      reducing the risk of surgical site infection. Application of security-gated
      management systems is an important and effective way to help ensure a clean,
      convenient, and safe management process to manage costs in the perioperative area
      and promote patient safety. 

PMID- 24875212
TI  - 10 years in, why time out still matters.

PMID- 24875213
TI  - Managing care interventions for the patient with COPD undergoing surgery.

PMID- 24875214
TI  - Standardization of tissue handling from the OR to the laboratory.

PMID- 24875216
TI  - Death by PCA.

PMID- 24875219
TI  - Isolation of the CH3 rotor in a thermally stable inert matrix: first
      characterization of the gradual transition from classical to quantum behaviour at
      low temperatures.
AB  - Matrix isolation is a method which plays a key role in isolating and
      characterizing highly reactive molecular radicals. However, the isolation
      matrices, usually composed of noble gases or small diamagnetic molecules, are
      stable only at very low temperatures, as they begin to desegregate even above a
      few tens of Kelvin. Here we report on the successful isolation of CH3 radicals in
      the cages of a nearly inert clathrate-SiO2 matrix. This host is found to exhibit
      a comparable inertness with respect to that of most conventional noble gas
      matrices but it is characterized by a peculiar thermal stability. The latter
      property is related to the covalent nature of the host material and gives the
      opportunity to study the confined radicals from a few degrees of Kelvin up to at
      least room temperature. Thanks to this advantage we were able to explore with
      continuity for the first time the CH3 rotor properties by electron paramagnetic
      resonance spectroscopy, starting from the quantum rotations which are observable
      only at the lowest temperatures (T ~ 4 K), going through the gradual transition
      to the classical motion (4 K < T < 30 K), and ending with the properties of the
      fully classical rotor (T > 30 K). The method of isolation presented here is found
      to be very effective and promising, as it is expected to be applicable to a large
      variety of different molecular radicals. 

PMID- 24875218
TI  - Clarification of the concept of Ganoderma orbiforme with high morphological
      plasticity.
AB  - Ganoderma has been considered a very difficult genus among the polypores to
      classify and is currently in a state of taxonomic chaos. In a study of Ganoderma
      collections including numerous type specimens, we found that six species namely
      G. cupreum, G. densizonatum, G. limushanense, G. mastoporum, G. orbiforme, G.
      subtornatum, and records of G. fornicatum from Mainland China and Taiwan are very
      similar to one another in basidiocarp texture, pilear cuticle structure, context
      color, pore color and basidiospore characteristics. Further, we sequenced the
      nrDNA ITS region (ITS1 and ITS2) and partial mtDNA SSU region of the studied
      materials, and performed phylogenetic analyses based on these sequence data. The
      nrDNA ITS sequence analysis results show that the eight nrDNA ITS sequences
      derived from this study have single-nucleotide polymorphisms in ITS1 and/or ITS2
      at inter- and intra-individual levels. In the nrDNA ITS phylogenetic trees, all
      the sequences from this study are grouped together with those of G. cupreum and
      G. mastoporum retrieved from GenBank to form a distinct clade. The mtDNA SSU
      sequence analysis results reveal that the five mtDNA SSU sequences derived from
      this study are clustered together with those of G. cupreum retrieved from GenBank
      and also form a distinct clade in the mtDNA SSU phylogenetic trees. Based on
      morphological and molecular data, we conclude that the studied taxa are
      conspecific. Among the names assigned to this species, G. fornicatum given to
      Asian collections has nomenclatural priority over the others. However, the type
      of G. fornicatum from Brazil is probably lost and a modern description based on
      the type lacks. The identification of the Asian collections to G. fornicatum
      therefore cannot be confirmed. To the best of our knowledge, G. orbiforme is the
      earliest valid name for use. 

PMID- 24875220
TI  - Highly accurate excited-state structure of [Os(bpy)2dcbpy](2+) determined by X
      ray transient absorption spectroscopy.
AB  - Determining the electronic and geometric structures of photoexcited transient
      species with high accuracy is crucial for understanding their fundamental
      photochemistry and controlling their photoreactivity. We have applied X-ray
      transient absorption spectroscopy to measure the XANES and EXAFS spectra of a
      dilute (submillimolar) solution of the osmium(II) polypyridyl complex
      [Os(bpy)2dcbpy](PF6)2 (dcbpy = 4,4'-dicarboxy-2,2'-bipyridine) (OsL2L') in
      methanol at the Os LIII edge. We have obtained spectra of superb quality for both
      the ground state and the photoinduced (3)MLCT excited state that have allowed us
      not only to extract detailed information about the Os 5d orbitals but also to
      resolve very small differences of 0.010 +/- 0.008 A in the average Os-N bond
      lengths of the ground and excited states. Theoretical calculations using a
      recently developed DFT-based approach support the measured electronic structures
      and further identify the nature of the molecular orbitals that contribute to the
      main absorption bands in the XANES spectra. 

PMID- 24875221
TI  - Telomere length - a cellular aging marker for depression and Post-traumatic
      Stress Disorder.
AB  - Telomeres play a central role in cell fate and aging by adjusting the cellular
      response to both biological and psychological stress. Human telomeres are regions
      of tandem TTAGGG repeats at chromosomal ends that protect chromosomes from
      degradation, fusion, and recombination. They are made up of approximately 1000
      2500 copies of the repeated DNA sequence. Over time, at each cell division, the
      telomere ends become shorter. Thus, telomere length (TL) has been considered a
      cellular marker for age-related diseases. In addition to biochemical stressors
      such as oxidation and inflammation, psychosocial traumatic stress has also been
      linked to shorter telomeres. TL is significantly inversely correlated with long
      term depression, even after controlling for age. Average TL in depressed
      subjects, who were above the median of lifetime depression, was 281 base pairs
      shorter than that in controls, corresponding to approximately 7years of
      accelerated cell aging. Several recent studies have also demonstrated an inverse
      relationship between leukocyte telomere length (LTL) and the risk of PTSD. TL was
      inversely correlated with the duration of caregiving and PTSD. Here, we focus on
      the discussion of findings in studies of the relationships between stress-related
      disorders (e.g., depression and PTSD) and telomeres. We also present direct
      evidence that TL is associated with traumatic stress, depression, and PTSD, and
      hypothesize that traumatic stress affects not only mental disorders but also
      cellular aging. The nature of this relationship between stress and TL warrants
      further evaluation in psychiatry. 

PMID- 24875222
TI  - Re: Spontaneously resolved exudative retinal detachment caused by orbital
      cellulitis in an immune compromised adult.

PMID- 24875223
TI  - Response to Perera and Ali.

PMID- 24875217
TI  - E3 ubiquitin ligase Cbl-b in innate and adaptive immunity.
AB  - Casitas B-lineage lymphoma proto-oncogene-b (Cbl-b), a RING finger E3 ubiquitin
      protein ligase, has been demonstrated to play a crucial role in establishing the
      threshold for T-cell activation and controlling peripheral T-cell tolerance via
      multiple mechanisms. Accumulating evidence suggests that Cbl-b also regulates
      innate immune responses and plays an important role in host defense to pathogens.
      Understanding the signaling pathways regulated by Cbl-b in innate and adaptive
      immune cells is therefore essential for efficient manipulation of Cbl-b in
      emerging immunotherapies for human disorders such as autoimmune diseases,
      allergic inflammation, infections, and cancer. In this article, we review the
      latest developments in the molecular structural basis of Cbl-b function, the
      regulation of Cbl-b expression, the signaling mechanisms of Cbl-b in immune
      cells, as well as the biological function of Cbl-b in physiological and
      pathological immune responses in animal models and human diseases. 

PMID- 24875224
TI  - Safety of Brilliant Blue G.

PMID- 24875226
TI  - On the safety profile of Ocublue Plus (BBG 0.05%).

PMID- 24875225
TI  - Intravitreal bevacizumab in the treatment of vasoproliferative retinal tumours.
AB  - AIM: To evaluate the efficacy of intravitreal bevacizumab in the treatment of
      retinal vasoproliferative tumours (VPT). MATERIALS AND METHODS: Six eyes of 6
      patients with VPT who received intravitreal bevacizumab were retrospectively
      reviewed. All patients received between one and three injections of intravitreal
      bevacizumab depending upon response to treatment. Best-corrected visual acuity
      (BCVA), tumour size, and presence of co-pathology or sequelae were noted pre- and
      postoperatively and then analysed. Subsequent retreatments were performed in
      patients with recurrent or persistent VPT according to the ophthalmologist's
      discretion. Retreatments included photodynamic therapy with verteporfin,
      ruthenium-106 plaque brachytherapy, or endoresection of tumour. RESULTS: The mean
      follow-up duration was 33.3 months (range 10-66 months). At baseline, the mean
      logMAR BCVA was 1.45 (Snellen equivalent of 6/165); range 0.10-1.90 (6/8-CF).
      Following bevacizumab treatment the mean logMAR BCVA was 0.98 (Snellen equivalent
      of 6/57); range 0.5-1.9 (Snellen equivalent of 6/19 to CF). Therefore, there was
      no statistically significant change in visual acuity. The mean tumour thickness
      reduced from 2.4 to 2.1 mm following treatment with bevacizumab. However, this
      did not reach the statistical significance of P<0.05. Despite the visual
      improvement following bevacizumab therapy, five out of six patients had
      recurrence of tumour activity during the follow-up period and required further
      intervention in order to achieve sustained regression. CONCLUSIONS: Intravitreal
      bevacizumab appeared to result in temporary reduction of tumour thickness in 3
      out of 6 VPT patients. However, neither the reduction in tumour thickness nor the
      change in visual acuity were statistically significant and intravitreal
      bevacizumab monotherapy had limited effectiveness in causing long-term regression
      of the lesions. Additional therapy was indicated in five out of six patients to
      establish long-term regression. The efficacy of bevacizumab as an adjunct is as
      yet undetermined and further studies are needed. Presently, we recommend other
      treatment modalities in the long-term management of VPTs.

PMID- 24875227
TI  - Portsmouth visual field database: an audit of glaucoma progression.
AB  - AIM: To explore visual field (VF) progression in a cohort of secondary care
      treated glaucoma and ocular hypertensive (OHT) patients. METHODS: We extracted
      VFs from our database drawn from our normal clinical practice. VF series from
      4177 eyes from 2208 patients who had five or more VFs were obtained, the 'better'
      eye was selected and the rate of VF progression was calculated using mean
      deviation (MD) data. RESULTS: The median rate of progression for the whole sample
      was -0.1 dB/year (interquartile range (IQR) -4 to 0 dB/year) over a median of 6.7
      years (IQR 4.9-8.7). Of 2208 patients, 477 (21.2%) progressed at > -0.5 dB/year;
      46 (2.1%) progressed at >-2.0 dB/year. Of those with a 'final MD' of worse than 
      10 dB (N=244) in their better eye; 14.0% were 'fast progressors' (>-2 dB/year),
      33.7% 'moderate progressors' (-1 to -2 dB/year), and 28.8% 'slow progressors' (
      0.3 dB to -1 dB/year). Of those with 'initial MD' better than -3 dB and those
      with worse than -3 dB, 31/1679 (1.8%) and 213/529 (40.3%) respectively, had a
      final MD of worse than -10 dB. CONCLUSION: Fast progressors, while important, are
      relatively rare. Moderate and slow progressors make up the majority of the
      progressing population within this data set. The risk of significant visual loss
      is much higher in those with initial damage. With increasing life expectancy,
      moderate and slow progressors may become increasingly clinically important.

PMID- 24875228
TI  - The impact of new methods of investigation and treatment on the understanding of
      the pathology of scleral inflammation.
AB  - Recent advances in the understanding of the initiation and perpetuation of the
      immune response strongly suggest that all forms of noninfective immunologically
      induced scleral inflammation have a common origin. Analysis of the progress of
      patients with scleritis corroborates the current clinical classification that,
      together with studies of the immunohistology fluoresceine/ICG angiography, 3D
      proteoglycan, and keratan sulphate electron microscopy of scleritis, strongly
      suggests that from the initiation of the inflammatory process, necrotizing
      scleritis and diffuse and nodular scleritis not only pursue a different course
      but also have a different pathogenesis; nonnecrotizing scleritis being the
      consequence of an auto immune response, whereas necrotizing scleritis being the
      complication of an already present (if not always manifest), systemic immune
      mediated systemic disease and its associated vasculitis. The increasing imaging
      capacity of anterior segment ocular coherence tomography (OCT) and en face OCT
      enables the changes occurring in the sclera during the course of the disease to
      be observed for the first time. These observations suggest that the inflammatory
      changes involve the potential suprachoroidal space between choroid and sclera, an
      observation supported by the presence of subscleral granulomas on histopathology.
      New imaging techniques have also been able to explain the changes seen in the
      cornea as a complication of scleritis. These findings have implications for
      investigation and the treatment of these conditions. 

PMID- 24875229
TI  - Localized peripheral primitive neuroectodermal tumor of the conjunctiva: a rare
      presentation.

PMID- 24875230
TI  - Syntheses and radiosyntheses of two carbon-11 labeled potent and selective
      radioligands for imaging vesicular acetylcholine transporter.
AB  - PURPOSE: The vesicular acetylcholine transporter (VAChT) is a specific biomarker
      for imaging presynaptic cholinergic neurons. The syntheses and C-11 labeling of
      two potent enantiopure VAChT inhibitors are reported here. PROCEDURES: Two VAChT
      inhibitors, (+/-)-2 and (+/-)-6, were successfully synthesized. A chiral HPLC
      column was used to resolve the enantiomers from each corresponding racemic
      mixture for in vitro characterization. The radiosyntheses of (-)-[(11)C]2 and (-)
      [(11)C]6 from the corresponding desmethyl phenol precursor was accomplished using
      [(11)C]methyl iodide or [(11)C]methyl triflate, respectively. RESULTS: The
      synthesis of (-)-[(11)C]2 was accomplished with 40-50 % radiochemical yield
      (decay-corrected), SA > 480 GBq/MUmol (EOB), and radiochemical purity >99 %.
      Synthesis of (-)-[(11)C]6 was accomplished with 5-10 % yield, SA > 140 GBq/MUmol
      (EOB), and radiochemical purity >97 %. The radiosynthesis and dose formulation of
      each tracer was completed in 55-60 min. CONCLUSIONS: Two potent enantiopure VAChT
      ligands were synthesized and (11)C-labeled with good radiochemical yield and
      specific activity.

PMID- 24875232
TI  - The association between having a first-degree family history of cancer and
      smoking status.
AB  - OBJECTIVE: A diagnosis of cancer within the family provides an opportunity for
      smokers to adopt a health-promoting behavior. This study examines the
      associations between having a first-degree family history of cancer and smoking
      status using population-based data with a large and diverse sample. METHOD: Cross
      sectional data from the 2009 California Health Interview Survey on 47,331 adults
      were analyzed. Sample weights were applied to account for the survey design with
      results generalizable to non-institutionalized adults in California (27.4
      million). RESULTS: In 2009, 3.7 million (13.6%) adults were current-smokers, 6.3
      million (23.0%) were former smokers and 17.4 million (63.4%) were never-smokers.
      Nine-million-six-hundred-thousand (35%) had a first-degree family history of
      cancer. Controlling for all covariates, first-degree family history of cancer was
      significantly associated with being a current smoker (OR=1.16; 95% CI=1.01-1.35)
      and to being a former smoker (OR=1.17; 95% CI=1.05-1.30). CONCLUSION: In
      California, although many adults with a first-degree family history of cancer
      quit smoking, a significant subset still smoke which places them at higher risk
      for poor health outcomes. This subset represents an important target population
      for smoking cessation interventions.

PMID- 24875231
TI  - Neighborhood-level socioeconomic deprivation predicts weight gain in a multi
      ethnic population: longitudinal data from the Dallas Heart Study.
AB  - OBJECTIVE: The aim of this study is to examine a relationship between
      neighborhood-level socioeconomic deprivation and weight change in a multi-ethnic
      cohort from Dallas County, Texas and whether behavioral/psychosocial factors
      attenuate the relationship. METHODS: Non-movers (those in the same neighborhood
      throughout the study period) aged 18-65 (N=939) in Dallas Heart Study (DHS)
      underwent weight measurements between 2000 and 2009 (median 7-year follow-up).
      Geocoded home addresses defined block groups; a neighborhood deprivation index
      (NDI) was created (higher NDI=greater deprivation). Multi-level modeling
      determined weight change relative to NDI. Model fit improvement was examined with
      adding physical activity and neighborhood environment perceptions (higher
      score=more unfavorable perceptions) as covariates. A significant interaction
      between residence length and NDI was found (p-interaction=0.04); results were
      stratified by median residence length (11 years). RESULTS: Adjusting for age,
      sex, race/ethnicity, smoking, and education/income, those who lived in
      neighborhood >11 years gained 1.0 kg per one-unit increment of NDI (p=0.03), or 6
      kg for those in highest NDI tertile compared with those in the lowest tertile.
      Physical activity improved model fit; NDI remained associated with weight gain
      after adjustment for physical activity and neighborhood environment perceptions.
      There was no significant relationship between NDI and weight change for those in
      their neighborhood <=11 years. CONCLUSIONS: Living in more socioeconomically
      deprived neighborhoods over a longer time period was associated with weight gain
      in DHS.

PMID- 24875233
TI  - Comparing the effect of hypercapnia and hypoxia on the electroencephalogram
      during wakefulness.
AB  - OBJECTIVE: Hypoxia has been postulated as a key mechanism for neurocognitive
      impairment in sleep-disordered breathing. However, the effect of hypoxia on the
      electroencephalogram (EEG) is not clear. METHODS: We examined quantitative EEG
      recordings from 20 normal volunteers under three 5-min ventilatory control
      protocols: progressive hypercapnia with iso-hyperoxia (pO2=150mmHg) (Protocol 1),
      progressive hypercapnia with iso-hypoxia (pO2=50mmHg) (Protocol 2), and
      progressive hypoxia with a CO2 scrubber in the circuit (Protocol 3). Each
      protocol started with a 5-min session of breathing room air as baseline. RESULTS:
      In Protocol 1, compared to its baseline, iso-hyperoxia hypercapnia led to a lower
      Alpha% and higher Delta/Alpha (D/A) ratio. Similarly, in Protocol 2, the iso
      hypoxia hypercapnia induced a higher Delta%, a lower Alpha% and higher D/A ratio.
      No difference was found in any EEG spectral band including the D/A ratio when
      Protocols 1 & 2 were compared. In Protocol 3, the Delta%, Alpha% and D/A ratio
      recorded during hypoxia were not significantly different from baseline.
      CONCLUSIONS: We found that hypercapnia, but not hypoxia, may play a key role in
      slowing of the EEG in healthy humans. SIGNIFICANCE: Hypercapnia may be a greater
      influence than hypoxia on brain neuroelectrical activities.

PMID- 24875234
TI  - Excellent interrater agreement for the differentiation of fasciculations and
      artefacts - a dynamic myosonography study.
AB  - OBJECTIVE: The aim of the study was to confirm the diagnostic performance of
      dynamic myosonography with regard to its reliability to correctly identify
      fasciculations and to distinguish them from artefacts. Furthermore, interrater
      agreement regarding the identification of different muscle movements was
      investigated. METHODS: A total of 11 observers analysed 25 muscle ultrasound
      videos acquired using a standardized protocol. The video files illustrated
      fasciculations and artefacts (voluntary probe movements, voluntary contractions
      or swallowing and pulsating vessels) in different muscle groups. RESULTS:
      Fasciculations could be distinguished from artefacts with a sensitivity of 90.9%
      and specificity of 98.5%. Interrater agreement regarding the presence or absence
      of fasciculations showed an overall median of 100% (interquartile range, IQR: 96
      100%). In every investigated muscle group, the median of the interpreter
      agreement was found to be 100% (correct ratings of all observers: submental
      muscles: 43 of 44; biceps muscles: 22 of 22; forearm flexors: 31 of 33; rectus
      abdominis muscles: 33 of 33; quadriceps muscles: 19 of 22; tibialis anterior
      muscles: 51 of 55; undefinable muscles: 65 of 66). CONCLUSION: Dynamic
      myosonography is an extremely reliable tool with excellent interrater agreement
      to correctly identify fasciculations and to distinguish them from artefacts.
      SIGNIFICANCE: Myosonography should be further incorporated in clinical routine
      diagnostic work-up.

PMID- 24875235
TI  - Juvenile idiopathic arthritis subtype- and sex-specific associations with genetic
      variants in the PSMA6/PSMC6/PSMA3 gene cluster.
AB  - BACKGROUND: The ubiquitin proteasome system plays an exceptional biological role
      in the antigen processing and immune response and it could potentially be
      involved in pathogenesis of many immunity-related diseases, including juvenile
      idiopathic arthritis (JIA). METHODS: The PSMB5 (rs11543947), PSMA6 (rs2277460,
      rs1048990), PSMC6 (rs2295826, rs2295827), and PSMA3 (rs2348071) proteasomal genes
      were genotyped on JIA subtype- and sex-specific association; plasma proteasome
      levels was measured in patients having risk and protective four-locus genotypes
      and eventual functional significance of allele substitutions was evaluated in
      silico. RESULTS: Loci rs11543947 and rs1048990 were identified as disease neutral
      and other loci as disease susceptible (p < 0.05). The rs2277460, rs2295826, and
      rs2295827 loci had the strongest association with oligoarthritis [odds ratio (OR)
      = 2.024, 95% confidence interval (CI) 1.101-3.722; OR = 2.371, 95% CI 1.390
      4.044; OR = 2.183, 95% CI 1.272-2.737, respectively), but the rs2348071 locus was
      associated with polyarthritis in females (OR = 3.438, 95% CI 1.626-7.265). A
      strong (p < 0.001) association was detected between the
      rs2277460/rs2295826/rs2295827/rs2348071 four-locus genotypes and the healthy
      phenotype when all loci were homozygous on common alleles (OR 0.439, 95% CI 0.283
      0.681) and with the disease phenotype when the rs2348071 and the rs2295826 and/or
      rs2295827 loci were represented by risk genotypes simultaneously (OR 4.674, 95%
      CI 2.096-10.425). Rarely observed in controls, the double rs2277460/rs2348071
      heterozygotes were rather frequent in affected males and more strongly associated
      with polyarthritis (p < 0.05). Haplotypes carrying the rare rs2295826/rs2295827
      and rs2277460 alleles showed a strong (p < 0.001) association with oligo- and
      polyarthritis, respectively. The plasma proteasome level was found to be
      significantly higher in females having four-locus risk genotypes compared with
      protective genotypes (p < 0.001). Sequence affinity to transcription factors and
      similarity to splicing signals, microRNAs and/or hairpin precursors potentially
      depend on allele substitutions in disease susceptible loci. CONCLUSION: We
      demonstrate for the first time evidence of a sex-specific association of
      PSMA6/PSMC6/PSMA3 genetic variants with subtypes of JIA and plasma proteasome
      concentrations. Theoretical models of the functional significance of allele
      substitutions are discussed.

PMID- 24875236
TI  - Reevaluating reference ranges of oxygen saturation for healthy full-term neonates
      using pulse oximetry.
AB  - BACKGROUND: We compared our clinical experience with currently available
      reference oxygen saturation level (SpO(2)) values from the American Academy of
      Pediatrics/American Heart Association (AAP/AHA) neonatal resuscitation program
      guidelines. METHODS: We enrolled 145 healthy full-term neonates; infants showing
      respiratory distress and those with serious congenital anomalies were excluded.
      SpO(2) values at every 1 minute until 10 minutes after birth were measured and
      recorded. Infants were classified into the cesarean section (CS) and normal
      spontaneous delivery (NSD) groups for evaluating differences. The 10(th)
      percentiles of SpO(2) at each minute were used as the lower limits of normal
      oxygen saturation, and these were compared with the lowest target values
      recommended in the AAP/AHA guidelines. RESULTS: Overall, 130 vigorous full-term
      neonates (median gestational age: 38 5/7 weeks; body weight at birth: 2405-3960
      g) were analyzed. The median SpO(2) were 67% and 89% at the 1(st) and 4(th)
      minute, respectively. On average, SpO(2) values reached >90% at the 5(th) minute.
      No statistical differences were noted in the SpO(2) values between the CS and NSD
      groups after 5 minutes; however, a trend of higher SpO(2) was observed in the NSD
      group. We noted a gradually increasing trend for SpO(2) values over time, similar
      to that noted in the AAP/AHA guidelines. However, SpO(2) values at the 10(th)
      percentiles of each minute within the first 5 minutes in our study were equal to
      or significantly lower than those in the AAP/AHA guidelines; moreover, at the
      10(th) minute, SpO(2) values at the 10(th) percentiles were significantly higher
      than those in the guidelines. CONCLUSION: The delivery modes did not affect the
      SpO(2) values of full-term healthy neonates. Discrepancies in SpO(2) changes in
      full-term neonates not requiring resuscitation between this study and the AAP/AHA
      guidelines were significant. SpO(2) ranges for each time point within the first
      10 minutes after birth should therefore be reevaluated locally.

PMID- 24875237
TI  - Kidney function assessment and its role in drug development, review and
      utilization.
AB  - A key regulatory requirement pertaining to drug development is characterization
      of the role of kidney function in drug disposition and response, along with
      provision of corresponding renal dose adjustment recommendations. Traditionally,
      this information has been derived from Phase I pharmacokinetic studies in which
      regulatory guidance exists for pharmaceutical manufacturers on the design,
      conduct, analysis, and interpretation of data. Categorization and stratification
      of subjects into kidney function groups and dosing recommendations have
      historically been based on creatinine clearance estimates using the Cockcroft
      Gault equation. As new estimating equations have emerged, the choice of equation
      for assessment of kidney function has become an area of debate. This review
      highlights these equations and provides recent examples of the use of
      quantitative models, incorporating efficacy and safety to make rational dose
      recommendations in subjects with impaired kidney function.

PMID- 24875238
TI  - Difficulties in everyday life: young persons with attention-deficit/hyperactivity
      disorder and autism spectrum disorders perspectives. A chat-log analysis.
AB  - This study focuses on the everyday life of young persons with attention
      deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). There
      are follow-up studies describing ADHD, and ASD in adults, and residual
      impairments that affect life. Few qualitative studies have been conducted on the
      subject of their experiences of everyday life, and even fewer are from young
      persons' perspectives. This study's aim was to describe how young persons with
      ADHD and ASD function and how they manage their everyday life based on analyses
      of Internet-based chat logs. Twelve young persons (7 males and 5 females aged 15
      26) diagnosed with ADHD and ASD were included consecutively and offered 8 weeks
      of Internet-based Support and Coaching (IBSC). Data were collected from 12 chat
      logs (445 pages of text) produced interactively by the participants and the
      coaches. Qualitative content analysis was applied. The text was coded and sorted
      into subthemes and further interpreted into themes. The findings revealed two
      themes: "fighting against an everyday life lived in vulnerability" with the
      following subthemes: "difficult things," "stress and rest," and "when feelings
      and thoughts are a concern"; and the theme "struggling to find a life of one's
      own" with the following subthemes: "decide and carry out," "making life choices,"
      and "taking care of oneself." Dealing with the problematic situations that
      everyday encompasses requires personal strength and a desire to find adequate
      solutions, as well as to discover a role in society. This study, into the
      provision of support and coaching over the Internet, led to more in-depth
      knowledge about these young persons' everyday lives and revealed their ability to
      use IBSC to express the complexity of everyday life for young persons with ADHD
      and ASD. The implications of the findings are that using online coaching makes
      available new opportunities for healthcare professionals to acknowledge these
      young persons' problems. 

PMID- 24875239
TI  - The benefits of in-group contact through physical activity involvement for health
      and well-being among Korean immigrants.
AB  - This qualitative study is designed to examine the benefits of physical activity
      involvement with members of the same ethnic group. For this study, Korean
      immigrants who were members of Korean physical activity clubs such as badminton
      and tennis were selected as participants. Using a constructive grounded theory
      methodology, three themes were identified as benefits of physical activity
      involvement: (1) the experience of psychological well-being, (2) the creation of
      a unique cultural world, and (3) the facilitation of physical activity
      involvement. The findings of this study suggest that Korean immigrant
      participants gained various social, cultural, and psychological benefits by
      engaging in activities with other Korean immigrants. 

PMID- 24875241
TI  - Prognosis: how long do we wait for the doctor?

PMID- 24875242
TI  - Symptoms and palliative care needs of pancreatic adenocarcinoma patients.

PMID- 24875243
TI  - Dexmedetomidine #280.

PMID- 24875244
TI  - A radiation oncologist's story: high tech meets high touch.

PMID- 24875245
TI  - High school reunion.

PMID- 24875246
TI  - A quiet story.

PMID- 24875247
TI  - One round.

PMID- 24875248
TI  - Efficient Expansion of Dissociated Human Pluripotent Stem Cells Using a Synthetic
      Substrate.
AB  - Human pluripotent stem cells (hPSCs), including human embryonic stem cells and
      human-induced pluripotent stem cells, are a renewable cell source for a wide
      range of applications in regenerative medicine and useful tools for human disease
      modeling and drug discovery. For these purposes, large numbers of high-quality
      cells are essential. Recently, we showed that a biological substrate, recombinant
      E8 fragments of laminin isoforms, sustains long-term self-renewal of hPSCs in
      defined, xeno-free medium with dissociated single-cell passaging. Here, we
      describe a modified culture system with similar performance to efficiently expand
      hPSCs under defined, xeno-free conditions using a non-biological synthetic
      substrate. 

PMID- 24875249
TI  - Fabrication of biofunctionalized, cell-laden macroporous 3D PEG hydrogels as bone
      marrow analogs for the cultivation of human hematopoietic stem and progenitor
      cells.
AB  - In vitro proliferation of hematopoietic stem cells (HSCs) is yet an unresolved
      challenge. Found in the bone marrow, HSCs can undergo self-renewing cell division
      and thereby multiply. Recapitulation of the bone marrow environment in order to
      provide the required signals for their expansion is a promising approach.Here, we
      describe a technique to produce biofunctionalized, macroporous poly(ethylene
      glycol) diacrylate (PEGDA) hydrogels that mimic the spongy 3D architecture of
      trabecular bones, which host the red, blood-forming bone marrow. After seeding
      these scaffolds with cells, they can be used as simplified bone marrow analogs
      for the cultivation of HSCs. This method can easily be conducted with standard
      laboratory chemicals and equipment. The 3D hydrogels are produced via salt
      leaching and biofunctionalization of the material is achieved by co-polymerizing
      the PEGDA with an RGD peptide. Finally, cell seeding and retrieval are described.

PMID- 24875251
TI  - Molecular phylogeny and biogeography of air sac catfishes of the Heteropneustes
      fossilis species complex (Siluriformes: Heteropneustidae).
AB  - The air sac catfish, Heteropneustes fossilis (Siluriformes: Heteropneustidae), is
      widely distributed in freshwaters of the Indian subcontinent and mainland
      southeast Asia. No comprehensive molecular studies that cover the broad
      distributional areas have been carried out to date. Here, we conducted molecular
      phylogenetic analyses using both mitochondrial and nuclear gene sequences to
      suggest that the Heteropneustes fossilis species complex consists of three clades
      that may potentially be separate species with distinct geographical distribution
      (southeast Asia, northeastern India, and southwestern India). The first and
      second clades are more closely related to each other than they are to the third
      clade. Within the first clade there is a basal divergence of a subclade
      consisting of individuals from the Upper Irrawaddy River basin of Myanmar, which
      share some morphological traits with members of the Indian clades. Our molecular
      and morphological data are congruent with hypotheses that the Early-Middle
      Miocene disconnection between the paleo-Tsangpo River and the Irrawaddy River
      caused the vicariant divergence between southeast Asian and northeastern Indian
      clades, and that the southeast Asian Heteropneustes originated from the Upper
      Irrawaddy. 

PMID- 24875250
TI  - Association of serum levels of CEA, CA199, CA125, CYFRA21-1 and CA72-4 and
      disease characteristics in colorectal cancer.
AB  - Identifying predictive biomarkers for colorectal cancer would facilitate
      diagnosis and treatment of the disease. This study aimed to investigate the
      association of the serological biomarkers CEA, CA19-9, CA125, CYFRA21-1 and CA72
      4 with patient characteristics and disease outcomes in colorectal cancer.
      Patients (N = 373) with colorectal cancer were evaluated for the association of
      CEA, CA19-9, CA125, CYFRA21-1, and CA72-4 pre and post-surgery and at disease
      recurrence with demographics, disease characteristics including pathological
      types, degree of differentiation, invasion depth, abdominal lymph node
      metastasis, TMN stage, Dukes stage, location of cancer and metastasis, and
      disease outcomes. It was more common for a patient to express these markers prior
      to surgery and at disease recurrence than following surgery. Overall, the serum
      levels of CEA, CA19-9, CA125, CYFRA21-1, and CA72-4 were not associated with age,
      gender, pathological type and location of cancer (all P-values >0.05), but were
      associated with the poor tumor differentiation, higher tumor invasion, greater
      degree of abdominal lymph node metastasis, and higher TNM and Duke stage tumors
      (all P-values < 0.01). CEA expression was associated with older ages (median age
      65 years). Multivariate analysis indicated that CEA was correlated with overall
      survival and none of the markers correlated with disease recurrence. The
      expression of CEA, CA19-9, CA125, CYFRA21-1, and CA72-4 was associated with
      specific disease characteristics which tended to indicated more advanced disease
      and disease recurrence consistent with these biomarkers being useful for
      detecting colorectal cancer.

PMID- 24875252
TI  - Antitropical distributions and species delimitation in a group of ophiocomid
      brittle stars (Echinodermata: Ophiuroidea: Ophiocomidae).
AB  - In this paper we examine the phylogeny and biogeography of the temperate genera
      of the Ophiocomidae (Echinodermata: Ophiuroidea) which have an interesting
      asymmetrical anti-tropical distribution, with two genera (Ophiocomina and
      Ophiopteris) previously considered to have a separate species in both the North
      and South hemispheres, and the third (Clarkcoma) diversifying in the southern
      Australian/New Zealand region. Our phylogeny, generated from one mitochondrial
      and two nuclear markers, revealed that Ophiopteris is sister to a mixed
      Ophiocomina/Clarkcoma clade. Ophiocomina was polyphyletic, with O. nigra and an
      undescribed species from the South Atlantic Ocean sister to a clade including
      Clarkcoma species and O. australis. The phylogeny also revealed a number of
      recently diverged lineages occurring within Clarkcoma, some of which are
      considered to be cryptic species due to the similarity in morphology combined
      with the apparent absence of interbreeding in a sympatric distribution, while the
      status of others is less certain. The phylogeny provides support for two
      transequatorial events in the group under study. A molecular clock analysis
      places both events in the middle to late Miocene. The analysis excludes a
      tectonic vicariance hypothesis for the antitropical distribution associated with
      the breakup of Pangaea and also excludes the hypothesis of more recent gene flow
      associated with Plio/Pleistocene glacial cycling. 

PMID- 24875253
TI  - Heteroatoms ternary-doped porous carbons derived from MOFs as metal-free
      electrocatalysts for oxygen reduction reaction.
AB  - The nitrogen (N), phosphorus (P) and sulphur (S) ternary-doped metal-free porous
      carbon materials have been successfully synthesized using MOFs as templates
      (denoted as NPS-C-MOF-5) for oxygen reduction reaction (ORR) for the first time.
      The influences of porous carbons from carbonizing different MOFs and
      carbonization temperature on ORR have been systematically investigated. Due to
      the synergistic effect of N, P and S ternary-doping, the NPS-C-MOF-5 catalyst
      shows a higher onset potential as a metal-free electrocatalyst for ORR among the
      currently reported metal-free electrocatalysts, very close to the commercial Pt-C
      catalyst. In particular, the kinetic limiting current density of NPS-C-MOF-5
      catalyst at -0.6 V is up to approximate -11.6 mA cm(-2), which is 1.2 times
      higher than that of the commercial Pt-C catalyst. Furthermore, the outstanding
      methanol tolerance and excellent long-term stability of NPS-C-MOF-5 are superior
      to those of the commercial Pt-C catalyst for ORR in alkaline media. 

PMID- 24875256
TI  - Wyburn-Mason syndrome.

PMID- 24875254
TI  - Deep sequencing reveals novel Set7 networks.
AB  - BACKGROUND: Methyl-dependent regulation of transcription has expanded from a
      traditional focus on histones to encompass transcription factor modulation. While
      the Set7 lysine methyltransferase is associated with pro-inflammatory gene
      expression in vascular endothelial cells, genome-wide regulatory roles remain to
      be investigated. From initial characterization of Set7 as specific for methyl
      lysine 4 of H3 histones (H3K4m1), biochemical activity toward non-histone
      substrates has revealed additional mechanisms of gene regulation. RESULTS: mRNA
      Seq revealed transcriptional deregulation of over 8,000 genes in an endothelial
      model of Set7 knockdown. Gene ontology identified up-regulated pathways involved
      in developmental processes and extracellular matrix remodeling, whereas pathways
      regulating the inflammatory response as well as nitric oxide signaling were down
      regulated. Chromatin maps derived from ChIP-Seq profiling of H3K4m1 identified
      several hundred loci with loss of H3K4m1 at gene regulatory elements associated
      with an unexpectedly subtle effect on gene expression. Transcription factor
      network analysis implicated six previously described Set7 substrates in mRNA-Seq
      changes, and we predict that Set7 post-translationally regulates other
      transcription factors associated with vascular endothelial gene expression
      through the presence of Set7 amino acid methylation motifs. CONCLUSION: We
      describe a role for Set7 in regulating developmental pathways and response to
      stimuli (inflammation/immune response) in human endothelial cells of vascular
      origin. Set7-dependent gene expression changes that occurred independent of
      H3K4m1 may involve transcription factor lysine methylation events. The method of
      mapping measured transcriptional changes to transcription factors to identify
      putative substrates with strong associations to functional changes is applicable
      to substrate prediction for other broad-substrate histone modifiers.

PMID- 24875255
TI  - Assessing the ecotoxicological effects of long-term contaminated mine soils on
      plants and earthworms: relevance of soil (total and available) and body
      concentrations.
AB  - The interactions and relevance of the soil (total and available) concentrations,
      accumulation, and acute toxicity of several essential and non-essential trace
      elements were investigated to determine their importance in environmental soil
      assessment. Three plant species (T. aestivum, R. sativum, and V. sativa) and E.
      fetida were simultaneously exposed for 21 days to long-term contaminated soils
      collected from the surroundings of an abandoned pyrite mine. The soils presented
      different levels of As and metals, mainly Zn and Cu, and were tested at different
      soil concentrations [12.5, 25, 50, and 100% of contaminated soil/soil (w/w)] to
      increase the range of total and available soil concentrations necessary for the
      study. The total concentrations in the soils (of both As and metals) were better
      predictors of earthworm uptake than were the available concentrations. In plants,
      the accumulation of metals was related to the available concentrations of Zn and
      Cu, which could indicate that plants and earthworms accumulate elements from
      different pools of soil contaminants. Moreover, Zn and Cu, which are essential
      elements, showed controlled uptake at low concentrations. The external metal
      concentrations predicted earthworm mortality, whereas in plants, the effects on
      growth were correlated to the As and metal contents in the plants. In general,
      the bioaccumulation factors were lower at higher exposure levels, which implies
      the existence of auto-regulation in the uptake of both essential and non
      essential elements by plants and earthworms.

PMID- 24875257
TI  - Occurrence of multi-antibiotic resistant Pseudomonas spp. in drinking water
      produced from karstic hydrosystems.
AB  - Aquatic environments could play a role in the spread of antibiotic resistance
      genes by enabling antibiotic-resistant bacteria transferred through wastewater
      inputs to connect with autochthonous bacteria. Consequently, drinking water could
      be a potential pathway to humans and animals for antibiotic resistance genes. The
      aim of this study was to investigate occurrences of Escherichia coli and
      Pseudomonas spp. in drinking water produced from a karst, a vulnerable aquifer
      with frequent increases in water turbidity after rainfall events and run-offs.
      Water samples were collected throughout the system from the karstic springs to
      the drinking water tap during three non-turbid periods and two turbid events. E.
      coli densities in the springs were 10- to 1000-fold higher during the turbid
      events than during the non-turbid periods, indicating that, with increased
      turbidity, surface water had entered the karstic system and contaminated the
      spring water. However, no E. coli were isolated in the drinking water. In
      contrast, Pseudomonas spp. were isolated from the drinking water only during
      turbid events, while the densities in the springs were from 10- to 100-fold
      higher than in the non-turbid periods. All the 580 Pseudomonas spp. isolates
      obtained from the sampling periods were resistant (to between 1 and 10
      antibiotics), with similar resistance patterns. Among all the Pseudomonas
      isolated throughout the drinking water production system, between 32% and 86%
      carried the major resistance pattern: ticarcillin, ticarcillin-clavulanic acid,
      cefsulodin, and/or aztreonam, and/or sulfamethoxazol-trimethoprim, and/or
      fosfomycin. Finally, 8 Pseudomonas spp. isolates, related to the Pseudomonas
      putida and Pseudomonas fluorescens species, were isolated from the drinking
      water. Thus, Pseudomonas could be involved in the dissemination of antibiotic
      resistance via drinking water during critical periods. 

PMID- 24875258
TI  - Applications of stochastic models and geostatistical analyses to study sources
      and spatial patterns of soil heavy metals in a metalliferous industrial district
      of China.
AB  - An extensive soil survey was conducted to study pollution sources and delineate
      contamination of heavy metals in one of the metalliferous industrial bases, in
      the karst areas of southwest China. A total of 597 topsoil samples were collected
      and the concentrations of five heavy metals, namely Cd, As (metalloid), Pb, Hg
      and Cr were analyzed. Stochastic models including a conditional inference tree
      (CIT) and a finite mixture distribution model (FMDM) were applied to identify the
      sources and partition the contribution from natural and anthropogenic sources for
      heavy metal in topsoils of the study area. Regression trees for Cd, As, Pb and Hg
      were proved to depend mostly on indicators of anthropogenic activities such as
      industrial type and distance from urban area, while the regression tree for Cr
      was found to be mainly influenced by the geogenic characteristics. The FMDM
      analysis showed that the geometric means of modeled background values for Cd, As,
      Pb, Hg and Cr were close to their background values previously reported in the
      study area, while the contamination of Cd and Hg were widespread in the study
      area, imposing potentially detrimental effects on organisms through the food
      chain. Finally, the probabilities of single and multiple heavy metals exceeding
      the threshold values derived from the FMDM were estimated using indicator kriging
      (IK) and multivariate indicator kriging (MVIK). The high probabilities exceeding
      the thresholds of heavy metals were associated with metalliferous production and
      atmospheric deposition of heavy metals transported from the urban and industrial
      areas. Geostatistics coupled with stochastic models provide an effective way to
      delineate multiple heavy metal pollution to facilitate improved environmental
      management. 

PMID- 24875259
TI  - The role of litterfall in transferring Fukushima-derived radiocesium to a
      coniferous forest floor.
AB  - The deposition of Fukushima-derived radiocesium via falling litter in a
      coniferous forest 180 km downwind immediately following the nuclear power plant
      accident was investigated. The litterfall contribution to the transfer of
      radiocesium from the forest canopy to the forest floor was determined, and this
      pathway was compared with hydrological pathways. The results demonstrated that
      during the observation period, a total of approximately 5.5 kBq m(-2) of
      Fukushima-derived radiocesium was deposited on the forest floor through
      throughfall (53%), stemflow (2.3%) and litterfall (45%) routes. The data revealed
      that the contributions of hydrological pathways became less important as time
      passed. However, the litterfall route, which transferred approximately 31% (2.5+/
      0.6 kBq m(-2)) of the local fallout within the observation period, continued
      depositing radiocesium onto the forest floor.

PMID- 24875260
TI  - Polychlorinated biphenyls still pose significant health risks to northwest
      Atlantic harbor seals.
AB  - Polychlorinated biphenyls (PCBs) have been detected at relatively high
      concentrations in harbor seals, apex predators in the northwest Atlantic. As part
      of an ongoing assessment of the effects of PCBs on population health, we analyzed
      tri- to deca-PCBs in the liver of 56 harbor seals (6 adult males, 50 pups) and in
      11 blubber samples (4 adult males, 7 pups) and examined tissue-specific
      accumulation patterns, biomagnification potential, and toxic implications of
      current PCB concentrations. Hepatic ?30PCB concentrations (overall mean+/
      standard deviation: 76,860+/-111,800 ng/g lipid weight, lw) were higher than
      blubber concentrations (48,180+/-69,420 ng/g lw). Regional trends were suggestive
      of fresh PCB inputs from the industrialized, densely populated southern coast of
      New England versus the rural north. The lack of temporal trends confirmed that
      tissue concentrations of PCBs have plateaued since the early 1990s. Tissue
      distribution of PCBs varied significantly by age and, surprisingly by gender
      among the pups. Principal Component Analysis (PCA) revealed that lighter PCBs are
      selectively transferred from mother to pup blubber in relation to lipid
      solubility (log Kow), but heavier PCBs may be efficiently transferred during late
      lactation from mother to pup liver. Biomagnification factors (BMFs) for ?6PCBs
      from prey fish to adult male seals ranged from 90 to 547 in the liver and 88 to
      532 in the blubber, and suggested that molecular structure and metabolic capacity
      were more important influences than log Kow on the retention of PCBs. Blubber
      concentrations of ?30PCBs in 87% of the pups were an order of magnitude higher
      than recent toxic reference values (TRVs) calculated for ?154PCBs in nursing
      harbor seals, suggesting that the pups are at risk for PCB-mediated toxicity at a
      vulnerable stage of development. Given the recurring pattern of epizootics in
      these seals, the health of the population is of concern.

PMID- 24875261
TI  - Receptor modelling of airborne particulate matter in the vicinity of a major
      steelworks site.
AB  - In this study, the Multilinear Engine (ME-2) receptor model was applied to
      speciated particulate matter concentration data collected with two different
      measuring instruments upwind and downwind of a steelworks complex in Port Talbot,
      South Wales, United Kingdom. Hourly and daily PM samples were collected with
      Streaker and Partisol samplers, respectively, during a one month sampling
      campaign between April 18 and May 16, 2012. Daily samples (PM10, PM2.5, PM2.5-10)
      were analysed for trace metals and water-soluble ions using standard procedures.
      Hourly samples (PM2.5 and PM2.5-10) were assayed for 22 elements by Particle
      Induced X-ray Emission (PIXE). PM10 data analysis using ME-2 resolved 6 factors
      from both datasets identifying different steel processing units including
      emissions from the blast furnaces (BF), the basic oxygen furnace steelmaking
      plant (BOS), the coke-making plant, and the sinter plant. Steelworks emissions
      were the main contributors to PM10 accounting for 45% of the mass when including
      also secondary aerosol. The blast furnaces were the largest emitter of primary
      PM10 in the study area, explaining about one-fifth of the mass. Other source
      contributions to PM10 were from marine aerosol (28%), traffic (16%), and
      background aerosol (11%). ME-2 analysis was also performed on daily PM2.5 and
      PM2.5-10 data resolving 7 and 6 factors, respectively. The largest contributions
      to PM2.5-10 were from marine aerosol (30%) and blast furnace emissions (28%).
      Secondary components explained one-half of PM2.5 mass. The influence of
      steelworks sources on ambient particulate matter at Port Talbot was
      distinguishable for several separate processing sections within the steelworks in
      all PM fractions.

PMID- 24875262
TI  - Mechanism for the formation and microphysical characteristics of submicron
      aerosol during heavy haze pollution episode in the Yangtze River Delta, China.
AB  - In this paper we investigate a severe pollution episode that occurred in the
      Yangtze River Delta (YRD) region in January 2013. The episode was caused by the
      combination of anthropogenic emissions and unusual atmospheric circulation, the
      depression of strong cold air activities and the very unfavorable dispersion. The
      episode contained three haze events (haze1: Jan. 4-9, haze2: Jan. 10-13, and
      haze3: Jan. 14-16). In Nanjing, aerosol size distributions from 10nm to 10 MUm
      and chemical components of single particles from 0.2 to 2 MUm were measured with
      a Wide Range Particle Spectrometer (WPS) and a Single Particle Aerosol Mass
      Spectrometer (SPAMS), respectively. The results indicate that the mean PM2.5
      concentrations in the YRD region were greater than 110 MUg.m(-3). The highest
      PM2.5 concentration of 175.6 MUg.m(-3) occurred in Nanjing; the other cities had
      values in the range of 110.8-147.3 MUg.m(-3). The average PM2.5 concentrations
      were 58.3, 122.7, 145.4 and 154.7 MUg.m(-3) on clean and haze1, haze2 and haze3
      days, respectively. The highest PM2.5 values of 416.5, 415.5 and 300.5 MUg.m(-3)
      in Nanjing occurred during the three haze events. The spectra of the aerosol
      number concentrations had unimodal distributions on clean and haze days. The
      maximum surface area peaks were located at 0.5-0.7 MUm and had values of 419,
      1397, 1309 and 1378 MUm(2).cm(-3).nm(-1) on clean and haze1, haze2 and haze3
      days, respectively. The number concentrations of biomass/biofuel burning
      containing particles (biomass), organic carbon-containing particles (OC),
      elemental carbon-containing particles (EC), nitrate-containing particles
      (nitrate) and sulfate-containing particles (sulfate) increased significantly
      during the haze events. The chemical components of the aerosols during the haze1
      and haze2 events were similar to those on clean days, and variations were caused
      by local particle accumulations under poor diffusion conditions. The high EC
      particle concentration of 24.76% during the haze3 event was impacted by the
      pollutants transported from surrounding cities. In addition, the different
      chemical components showed distinct size distributions.

PMID- 24875263
TI  - Rural:urban inequalities in post 2015 targets and indicators for drinking-water.
AB  - Disparities in access to drinking water between rural and urban areas are
      pronounced. Although use of improved sources has increased more rapidly in rural
      areas, rising from 62% in 1990 to 81% in 2011, the proportion of the rural
      population using an improved water source remains substantially lower than in
      urban areas. Inequalities in coverage are compounded by disparities in other
      aspects of water service. Not all improved sources are safe and evidence from a
      systematic review demonstrates that water is more likely to contain detectable
      fecal indicator bacteria in rural areas. Piped water on premises is a service
      enjoyed primarily by those living in urban areas so differentiating amongst
      improved sources would exacerbate rural:urban disparities yet further. We argue
      that an urban bias may have resulted due to apparent stagnation in urban coverage
      and the inequity observed between urban and peri-urban areas. The apparent
      stagnation at around 95% coverage in urban areas stems in part from relative
      population growth - over the last two decades more people gained access to
      improved water in urban areas. There are calls for setting higher standards in
      urban areas which would exacerbate the already extreme rural disadvantage.
      Instead of setting different targets, health, economic, and human rights
      perspectives, We suggest that the focus should be kept on achieving universal
      access to safe water (primarily in rural areas) while monitoring progress towards
      higher service levels, including greater water safety (both in rural and urban
      areas and among different economic strata). 

PMID- 24875264
TI  - Elemental concentrations in deposited dust on leaves along an urbanization
      gradient.
AB  - Environmental health is an essential component of the quality of life in modern
      societies. Monitoring of environmental quality and the assessment of
      environmental risks are often species based on the elemental concentration of
      deposited dust. Our result suggested that stomata size and distribution were the
      most important factors influencing the accumulation of air contaminants in
      leaves. We found that the leaves' surfaces of Acer negundo and Celtis
      occidentalis were covered by a large number of trichomes, and these species have
      proven to be suitable biomonitors for atmospheric pollution difficult; these can
      be overcome using bioindicator species. Leaves of Padus serotina, Acer campestre,
      A. negundo, Quercus robur and C. occidentalis were used to assess the amount of
      deposited dust and the concentration of contaminants in deposited dust in and
      around the city of Debrecen, Hungary. Samples were collected from an urban,
      suburban and rural area along an urbanization gradient. The concentrations of Ba,
      Cu, Fe, Mn, Ni, Pb, S, Sr and Zn were determined in deposited dust using ICP-OES.
      Scanning electron microscopy (SEM) was used to explore the morphological
      structure and dust absorbing capacity of leaves. We found significant differences
      in dust deposition among species, and dust deposition correlated with trichomes'
      density. Principal component analysis (PCA) also showed a total separation of
      tree. 

PMID- 24875265
TI  - Experimental and theoretical studies on the effect of the oxo group in 1,4
      benzodiazepines.
AB  - Two families of regioisomeric 1,4-benzodiazepines, 4-benzyl-3H
      benzo[e][1,4]diazepin-5-ones and 4-benzoyl-4,5-dihydro-3H
      benzo[e][1,4]diazepines, have been synthesized through a similar Ugi/reduction
      cyclization sequence. Their conformation and stability depend on the position of
      the tautomeric imine/enamine equilibrium present in the diazepine nucleus, which
      in turn depends on the relative position of the carbonyl group adjacent to the
      nitrogen at the 4-position in the benzodiazepine system. Moreover, the
      electrophilic center on the imine tautomer is essential for the antitumor
      activity of some benzodiazepines as a DNA binding position. The mechanism of
      tautomerization in the presence or absence of the oxo group has been studied
      computationally using DFT methods (B3LYP/6-31G** level). 

PMID- 24875266
TI  - The role of ceramide chain length distribution on the barrier properties of the
      skin lipid membranes.
AB  - The skin barrier function is provided by the stratum corneum (SC). The lipids in
      the SC are composed of three lipid classes: ceramides (CERs), cholesterol (CHOL)
      and free fatty acids (FFAs) which form two crystalline lamellar structures. In
      the present study, we investigate the effect of CER chain length distribution on
      the barrier properties of model lipid membranes mimicking the lipid composition
      and organization of SC. The membranes were prepared with either isolated pig CERs
      (PCERs) or synthetic CERs. While PCERs have a wide chain length distribution, the
      synthetic CERs are quite uniform in chain length. The barrier properties were
      examined by means of permeation studies using hydrocortisone as a model drug. Our
      studies revealed a reduced barrier in lipid membranes prepared with PCERs
      compared to synthetic CERs. Additional studies revealed that a wider chain length
      distribution of PCERs results in an enhanced hexagonal packing and increased
      conformational disordering of the lipid tails compared to synthetic CERs, while
      the lamellar phases did not change. This demonstrates that the chain length
      distribution affects the lipid barrier by reducing the lipid ordering and density
      within the lipid lamellae. In subsequent studies, the effect of increased levels
      of FFAs or CERs with a long acyl chain in the PCERs membranes was also studied.
      These changes in lipid composition enhanced the level of orthorhombic packing,
      reduced the conformational disordering and increased the barrier of the lipid
      membranes. In conclusion, the CER chain length distribution is an important key
      factor for maintaining a proper barrier. 

PMID- 24875268
TI  - Enhancing animal welfare by creating opportunities for positive affective
      engagement.
AB  - In line with an increasing emphasis on promoting positive welfare states in
      animals, this review extends previous accounts of how recent affective
      neuroscience observations may be used to identify and then to encourage animals
      to engage in reward-motivated behaviours. The terms affective states or affects
      are used to mean the subjective experiences, feelings or emotions that may
      motivate animals to behave in goal-directed ways and which may accompany success
      or failure to achieve those goals. These motivational affects may be positive,
      experienced as rewarding or pleasurable, or negative, experienced as aversive or
      punishing. There are two overall types: homeostasis-related negative affects that
      reflect an animal's internal physiological state, and situation-related positive
      or negative affects that reflect an animal's perception of its external
      circumstances. The major emphasis is on positive situation-related affects, in
      particular those that are potentially associated with exploration, feeding and
      animal-to-animal affiliative behaviours. The review introduces the new concept of
      positive affective engagement which represents the experience animals may have
      when they actively respond to motivations to engage in rewarding behaviours, and
      it incorporates all associated affects that are positive. For example, it would
      represent a state of engaged aliveness that may attend an animal's goal-directed,
      energised exploration of and interactions with a stimulus-rich environment. It
      also represents some states of equally energised, highly focused predatory
      stalking by carnivores or the focused and engaged foraging by herbivores when
      they are grazing in natural environments where food sources are abundant.
      Positive affective engagement may also be anticipated to accompany some aspects
      of reciprocated affiliative interactions between animals, the dedicated maternal
      nurturing and care of young, the joyfulness of rough-and-tumble play, and the
      eroticism and orgasmic pleasures of sexual activity. It is argued that
      highlighting the genetically pre-programmed, affectively positive impulses to
      engage in reward-motivated activities such as these, and the positive affects
      that may attend different facets of the process, draws attention to a wider
      spectrum of welfare enhancing experiences than has hitherto been considered to be
      important to animals. These neuroscience-supported observations strengthen many
      prior inferences made from predominantly behaviour-based investigations of
      animals' preferences, aversions and priorities, the associated development of
      successful environmental enrichments and the inclusion of these, where
      practicable, in more recent codes of practice or welfare.

PMID- 24875267
TI  - The role of epidemiology in evidence-based policy making: a case study of tobacco
      use in youth.
AB  - PURPOSE: Sound public health policy is based on relevant and timely information.
      A brief review of the history of youth tobacco control illustrates the central
      role of epidemiology to inform policy choices and evaluate their consequences.
      METHODS: A narrative review was conducted. RESULTS: Epidemiologic studies have
      shown that most smokers begin as adolescents or young adults and individuals who
      reach their mid-20s as nonsmokers are unlikely to ever become smokers. This key
      recognition made it clear that long-term tobacco control must prevent initiation
      of smoking among youth. Over time, tobacco use prevention interventions have
      evolved, increasing in reach and effectiveness as they moved from initially
      focusing on the individual to an approach that targets both populations and
      communities. Effective interventions for preventing youth smoking include raising
      tobacco prices, clean indoor air laws, and intensive mass media campaigns.
      CONCLUSIONS: Great strides have been made in youth tobacco control but 18% of
      high-school students continue to smoke. It is up to epidemiologists, fellow
      scientists, practitioners, and advocates to assure that strategies that are known
      to work are fully implemented and to continue to find more successful solutions
      that can further lower the incidence of youth smoking initiation and can address
      new tobacco products and changing contexts.

PMID- 24875269
TI  - Preparation of ansa-metallocenes for production of poly(alpha-olefin) lubricants.
AB  - An ansa-zirconocene bearing methyl substituents at all positions adjacent to the
      bridgehead [(-C(Ph)HC(Ph)H-)(eta(5)-2,5-Me2C5H2)2ZrCl2] (4) was prepared in high
      yields (78%) through the reductive dimerization of 1,4-dimethyl-6-phenylfulvene
      utilizing ZrCl2.DME generated in situ. The structure of 4 was subsequently
      confirmed using X-ray crystallography. 4 exhibited excellent catalytic
      performance with regard to 1-decene oligomerization, which was carried out with
      the intention of preparing lubricant base stocks. High activities (21 * 10(6) g
      mol(-1) Zr h(-1) activity; TON = 150 000; TOF = 42 s(-1)) were observed at
      temperatures as high as 120  degrees C and the oligomer distribution was
      appropriate for lubricant application. The simulated distillation (SIMDIS) data
      confirmed that a wide range of oligomers were formed, ranging from the dimer (2
      mer) to 20-mer. A minimal amount of the dimer and oligomers larger than the 10
      mer was formed (13 and 25 wt%, respectively). Alternatively, a typical unbridged
      complex such as (eta(5)-nBuC5H4)2ZrCl2 primarily produced dimers (54 wt%),
      whereas the ansa-zirconocene (EBI)ZrCl2 primarily produced oligomers larger than
      10-mer (62 wt%). The methyl substituents at the positions adjacent to the
      bridgehead in 4 played a significant role in the catalytic performance. 

PMID- 24875270
TI  - Association of vitamin D receptor gene polymorphism with the risk of lung cancer:
      a meta-analysis.
AB  - Relationship between vitamin D receptor (VDR) gene polymorphism and the risk of
      lung cancer from the published reports are still conflicting. This study was
      conducted to evaluate the relationship between VDR TaqI (rs731236), BsmI
      (rs1544410) and ApaI (rs7975232) gene polymorphism and the risk of lung cancer
      using meta-analysis method. The association studies were identified from PubMed
      and Cochrane Library on 1 December 2013, and eligible investigations were
      included and synthesized using meta-analysis method. Six reports were recruited
      into this meta-analysis for the association of VDR gene polymorphism with lung
      cancer susceptibility. In the meta-analysis for ApaI gene polymorphism, AA
      genotype was associated with the risk of lung cancer in Asians. In the meta
      analysis for BsmI gene polymorphism, B allele, BB genotype and bb genotype were
      associated with lung cancer in Asians, and B allele bb genotype were associated
      with lung cancer risk in overall populations; furthermore, bb genotype was
      associated with lung cancer risk in Caucasians. In the meta-analysis for TaqI
      gene polymorphism, t allele and TT genotype were associated with lung cancer in
      overall populations and in Caucasians. In conclusion, B allele bb genotype t
      allele and TT genotype were associated with lung cancer risk in overall
      populations. AA genotype, B allele, BB genotype and bb genotype were associated
      with the risk of lung cancer in Asians. Furthermore, bb genotype t allele and TT
      genotype was associated with lung cancer risk in Caucasians. However, more
      studies should be conducted to confirm it.

PMID- 24875271
TI  - An efficient synthetic method and theoretical calculations of olmesartan methyl
      ether: study of biological function of AT1 antagonism.
AB  - The dissolution of the antihypertensive AT1 antagonist olmesartan in methanol
      generates in situ a new highly bioactive methyl ether analogue via SN1 mechanism
      involving an intramolecular proton transfer from carboxyl to hydroxyl group.
      Theoretical calculations confirmed the thermodynamic control preference of methyl
      ether versus the antagonistic product methyl ester. Alpha facile synthetic method
      for olmesartan methyl ether from olmesartan or olmesartan medoxomil is also
      described. Interestingly, the introduction of the methyl group to olmesartan did
      not alter its pharmacological properties. This observation opens new avenues in
      the synthesis of novel drugs, since hydroxyl and carboxylate groups have an
      orthogonal relationship in many drugs. 

PMID- 24875272
TI  - Effect of CYP3A5 genotype, steroids, and azoles on tacrolimus in a pediatric
      renal transplant population.
AB  - BACKGROUND: Numerous studies have described the impact of cytochrome P450 3A5
      (CYP3A5) genotype on Tacrolimus (TAC) exposure. The purpose of this study was to
      conduct a comprehensive analysis of genetic and non-genetic factors affecting the
      TAC dose-exposure relationship over the first year post pediatric renal
      transplant. METHODS: Data were collected retrospectively for the first year post
      transplant in pediatric renal transplant patients receiving TAC maintenance
      immunosuppression. The effect of CYP3A5 genotype (CYP3A5*3 and *6 alleles), age,
      azoles, and corticosteroids on TAC trough concentration normalized for dose (TAC
      Co/D ng/ml/mg/kg/day) was assessed using a linear mixed model. RESULTS: Over
      time, TAC Co/D was lower in recipients with CYP3A5*1/*3 genotype compared to
      those with CYP3A5*3/*3 genotype (44.5 +/- 14.4 vs. 107.6 +/- 6.4, p = 0.03),
      increased in patients >12 years of age compared to < 12 years (93.9 +/- 8.7 vs.
      53.1 +/- 12.9, p = 0.007), and decreased by concomitant corticosteroids (69.5 +/-
      12.7 vs. 89.9 +/- 20.0, p = 0.04). The observed increased TAC Co/D in the
      presence of azoles (271 +/- 41 vs. 111 +/- 91, p = 0.016) could be attributed to
      clotrimazole. CONCLUSIONS: Multiple factors, including CYP3A5 genotype, and age,
      influence TAC Co/D in pediatric kidney transplant recipients. Clotrimazole
      administered as troches also contribute to TAC Co/D variability.

PMID- 24875274
TI  - Separation and enrichment of enantiopure from racemic compounds using magnetic
      levitation.
AB  - Crystallization of a solution with high enantiomeric excess can generate a
      mixture of crystals of the desired enantiomer and the racemic compound. Using a
      mixture of S-/RS-ibuprofen crystals as a model, we demonstrated that magnetic
      levitation (MagLev) is a useful technique for analysis, separation and
      enantioenrichment of chiral/racemic products. 

PMID- 24875276
TI  - Mapping the force field of a hydrogen-bonded assembly.
AB  - Hydrogen bonding underpins the properties of a vast array of systems spanning a
      wide variety of scientific fields. From the elegance of base pair interactions in
      DNA to the symmetry of extended supramolecular assemblies, hydrogen bonds play an
      essential role in directing intermolecular forces. Yet fundamental aspects of the
      hydrogen bond continue to be vigorously debated. Here we use dynamic force
      microscopy (DFM) to quantitatively map the tip-sample force field for naphthalene
      tetracarboxylic diimide molecules hydrogen-bonded in two-dimensional assemblies.
      A comparison of experimental images and force spectra with their simulated
      counterparts shows that intermolecular contrast arises from repulsive tip-sample
      interactions whose interpretation can be aided via an examination of charge
      density depletion across the molecular system. Interpreting DFM images of
      hydrogen-bonded systems therefore necessitates detailed consideration of the
      coupled tip-molecule system: analyses based on intermolecular charge density in
      the absence of the tip fail to capture the essential physical chemistry
      underpinning the imaging mechanism. 

PMID- 24875275
TI  - Validity of diagnostic codes and prevalence of physician-diagnosed psoriasis and
      psoriatic arthritis in southern Sweden--a population-based register study.
AB  - OBJECTIVE: To validate diagnostic codes for psoriasis and psoriatic arthritis
      (PsA) and estimate physician-diagnosed prevalence of psoriasis and PsA in the
      Skane region, Sweden. METHODS: In the Skane Healthcare Register (SHR), all
      healthcare consultations are continuously collected for all inhabitants in the
      Skane region (population 1.2 million). During 2005-2010 we identified individuals
      with >=1 physician-consultations consistent with psoriasis (ICD-10). Within this
      group we also identified those diagnosed with PsA. We performed a validation by
      reviewing medical records in 100 randomly selected cases for psoriasis and
      psoriasis with PsA, respectively. Further, we estimated the pre- and post
      validation point prevalence by December 31, 2010. RESULTS: We identified 16 171
      individuals (psoriasis alone: n = 13 185, psoriasis with PsA n = 2 986). The
      proportion of ICD-10 codes that could be confirmed by review of medical records
      was 81% for psoriasis and 63% for psoriasis with PsA with highest percentage of
      confirmed codes for cases diagnosed >=2 occasions in specialized care. For 19%
      and 29% of the cases respectively it was not possible to determine diagnosis due
      to insufficient information. Thus, the positive predicted value (PPV) of one ICD
      10 code for psoriasis and psoriasis with PsA ranged between 81-100% and 63-92%,
      respectively. Assuming the most conservative PPV, the post-validation prevalence
      was 1.23% (95% CI: 1.21-1.25) for psoriasis (with or without PsA), 1.02% (95% CI:
      1.00-1.03) for psoriasis alone and 0.21% (95% CI: 0.20-0.22) for psoriasis with
      PsA. The post-validation prevalence of PsA in the psoriasis cohort was 17.3% (95%
      CI: 16.65-17.96). CONCLUSIONS: The proportion of diagnostic codes in SHR that
      could be verified varied with frequency of diagnostic codes and level of care
      highlighting the importance of sensitivity analyses using different case
      ascertainment criteria. The prevalence of physician-diagnosed psoriasis and PsA
      confirm other population-based studies, also after adjustment due to
      misclassification of disease.

PMID- 24875277
TI  - Preoperative study of the surface ECG for the prognosis of atrial fibrillation
      maze surgery outcome at discharge.
AB  - The Cox-maze surgery is an effective procedure for terminating atrial
      fibrillation (AF) in patients requiring open-heart surgery associated with
      another heart disease. After the intervention, regardless of the patient's
      rhythm, all are treated with oral anticoagulants and antiarrhythmic drugs prior
      to discharge. Furthermore, patients maintaining AF before discharge could also be
      treated with electrical cardioversion (ECV). In view of this, a preoperative
      prognosis of the patient's rhythm at discharge would be helpful for optimizing
      drug therapy planning as well as for advancing ECV therapy. This work analyzes 30
      preoperative electrocardiograms (ECGs) from patients suffering from AF in order
      to predict the Cox-maze surgery outcome at discharge. Two different
      characteristics of the AF pattern have been studied. On the one hand, the atrial
      activity (AA) organization, which provides information about the number of
      propagating wavelets in the atria, was investigated. AA organization has been
      successfully used in previous studies related to spontaneous reversion of
      paroxysmal AF and to the outcome of ECV. To assess organization, the dominant
      atrial frequency (DAF) and sample entropy (SampEn) have been computed. On the
      other hand, the second characteristic studied was the fibrillatory wave (f-wave)
      amplitude, which has been demonstrated to be a valuable indicator of the Cox-maze
      surgery outcome in previous studies. Moreover, this parameter has been obtained
      through a new methodology, based on computing the f-wave average power (fWP).
      Finally, all the computed indices were combined in a decision tree in order to
      improve prediction capability. Results for the DAF yielded a sensitivity (Se), a
      specificity (Sp) and an accuracy (Acc) of 61.54%, 82.35% and 73.33%,
      respectively. For SampEn the values were 69.23%, 76.00% and 73.33%, respectively,
      and for fWP they were 92.31%, 82.35% and 86.67%, respectively. Finally, the
      decision tree combining the three parameters analyzed improved the preoperative
      prognosis of the Cox-maze outcome with values of Se, Sp and Acc of 100%, 82.35%
      and 90%, respectively. As a consequence, the analysis of parameters related to
      the f-wave pattern, extracted from the preoperative ECG, has provided a
      considerable ability to predict the outcome of AF Cox-maze surgery at discharge. 

PMID- 24875278
TI  - Rapid analysis of trace volatile formaldehyde in aquatic products by
      derivatization reaction-based surface enhanced Raman spectroscopy.
AB  - Toxic formaldehyde is sometimes used illegally as a food preservative, however,
      on-site rapid analysis of trace formaldehyde in aquatic products remains a
      challenge. In this work, a simple on-site rapid quantification method for trace
      volatile formaldehyde in aquatic products was developed by a derivative reaction
      based surface enhanced Raman spectroscopy (SERS) technique coupled with a
      homemade portable purge-sampling device. Trace formaldehyde separated from
      complicated aquatic matrices via a purge-sampling procedure was reacted with a
      derivative reagent to produce a Raman-active analyte for consequent SERS
      analysis. Au/SiO2 nanoparticles (NPs) were employed as the enhancement substrate
      to achieve significant enhancement of Raman signal intensity. Conditions of
      derivative reaction and SERS detection were optimized in detail, and the
      selectivity of this analytical method was also evaluated based on related
      analogs. Under optimal conditions, an extremely low detection limit of 0.17 MUg
      L(-1) was achieved. Trace volatile formaldehyde can be found in fresh squid and
      shrimp samples without obvious matrix interference, and this was quantified to be
      0.13-0.21 mg kg(-1) using the described method. The recoveries of spiked aquatic
      product samples were found to be 70.0-89.1% with RSDs of 2.3-7.2% (n = 3). The
      results suggest that the proposed method is reliable and suitable for on-site
      rapid analysis of trace formaldehyde in aquatic products. 

PMID- 24875280
TI  - Graphene quantum dots, graphene oxide, carbon quantum dots and graphite
      nanocrystals in coals.
AB  - Six coal samples of different ranks have been used to prepare single-layer
      graphene quantum dots (S-GQDs). After chemical oxidation and a series of
      centrifugation separation, every coal could be treated into two fractions,
      namely, CoalA and CoalB. According to the characterization results of TEM, AFM,
      XRD, Raman and FTIR, CoalA was revealed to be mainly composed of S-GQDs, which
      have an average height of about 0.5 nm and an average plane dimension of about 10
      nm. The obtained S-GQDs showed excitation-dependent fluorescence and excellent
      electrochemiluminescence. CoalB was found to be some other carbon-based
      nanomaterials (CNMs), including agglomerated GQDs, graphene oxide, carbon quantum
      dots and agglomerated carbon nanocrystals. Generally, low-ranked coals might be
      more suitable for the preparation of S-GQDs. The production yield of S-GQDs from
      the six investigated coals decreased from 56.30% to 14.66% when the coal rank
      increased gradually. In contrast, high-ranked coals had high production yield of
      CoalB and might be more suitable for preparing other CNMs that were contained in
      CoalB, although those CNMs were difficult to separate from each other in our
      experiment. 

PMID- 24875279
TI  - Influences on domestic well water testing behavior in a Central Maine area with
      frequent groundwater arsenic occurrence.
AB  - In 2001 the Environmental Protection Agency (EPA) adopted a new standard for
      arsenic (As) in drinking water of 10 MUg/L, replacing the old standard of 50
      MUg/L. However, for the 12% of the U.S. population relying on unregulated
      domestic well water, including half of the population of Maine, it is solely the
      well owner's responsibility to test and treat the water. A mailed household
      survey was implemented in January 2013 in 13 towns of Central Maine with the goal
      of understanding the population's testing and treatment practices and the key
      behavior influencing factors in an area with high well-water dependency and
      frequent natural groundwater As. The response rate was 58.3%; 525 of 900 likely
      delivered surveys to randomly selected addresses were completed. Although 78% of
      the households reported that their well has been tested, half of it was more than
      5 years ago. Among the 58.7% who believe they have tested for As, most do not
      remember the results. Better educated, higher income homeowners who more recently
      purchased their homes are most likely to have included As when last testing.
      While households agree that water and As-related health risks can be severe, they
      feel low personal vulnerability and there are low testing norms overall.
      Significant predictors of including As when last testing include: having
      knowledge that years of exposure increases As-related health risks (risk
      knowledge), knowing who to contact to test well water (action knowledge),
      believing that regular testing does not take too much time (instrumental
      attitude), and having neighbors who regularly test their water (descriptive
      norm). Homeowners in As-affected communities have the tendency to underestimate
      their As risks compared to their neighbors. The reasons for this optimistic bias
      require further study, but low testing behaviors in this area may be due to the
      influence of a combination of norm, ability, and attitude factors and barriers.

PMID- 24875281
TI  - Suppression by geraniol of the growth of A549 human lung adenocarcinoma cells and
      inhibition of the mevalonate pathway in culture and in vivo: potential use in
      cancer chemotherapy.
AB  - Geraniol (G)-a natural compound present in the essential oils of many aromatic
      plants-has attracted interest for its potential antitumor effects. The molecular
      mechanisms of the growth inhibition and apoptosis induced by G in cancer cells,
      however, remain unclear. In this study, we investigated the effects of G on cell
      proliferation in culture in A549 cells and in vivo in those same tumor cells
      implanted in nude mice fed diets supplemented with 25, 50, and 75 mmol G/kg. We
      demonstrated that G caused a dose- and time-dependent growth inhibition of A549
      cells and tumor growth in vivo along with an induction of apoptosis. Moreover,
      further in vivo assays indicated that G decreased the levels of 3
      hydroxymethylglutarylcoenzyme-A reductase-the rate-limiting enzyme in
      cholesterogenesis-in a dose-dependent manner along with cholesterogenesis and
      cholesterolemia in addition to reducing the amount of membrane-bound Ras protein.
      These results showed that the doses of G used in this work, though nontoxic to
      animals, clearly inhibited the mevalonate pathway, which is closely linked to
      cell proliferation and increased apoptosis in A549 tumors, but not in normal
      mouse-liver cells. Accordingly, we suggest that G displays significant antitumor
      activity and should be a promising candidate for cancer chemotherapy.

PMID- 24875282
TI  - Influence of emotional balance during a learning and recall test in horses (Equus
      caballus).
AB  - Modern day horse-human relationships entail different types of sport and riding
      activities, which all require learning. In evaluating the interaction between
      learning and emotions, studying normal coping strategies or adaptive responses to
      the surroundings is critical. 34 horses were involved in a cognitive test, in the
      absence of physical effort, to analyze performance, as well as physiological and
      behavioral responses related to learning, memorization and recall, associated to
      the capacity to reverse a learned model. Synthetic Equine Appeasing Pheromone
      (EAP) was used in 17 horses in order to modulate their emotional state and
      evaluate differences in cognitive-emotional response during cognitive effort in
      comparison to the control group (placebo group). Both groups showed statistically
      significant changes in heart rate during the test, indicating emotional and
      physio-cognitive activation. The EAP group produced fewer errors and made more
      correct choices, showing behaviors related to increased attention, with less
      influence from environmental stimuli. The capacity to learn to learn, as shown in
      the bibliography, allows animals to establish conceptual learning, when a normal
      or positive emotional state (in this case modulated by semiochemicals) is used to
      control limbic system activation and, consequently, decrease stressful/fearful
      reactions, resulting in better learning capacities during the cognitive test. 

PMID- 24875284
TI  - An analog VLSI implementation of the inner hair cell and auditory nerve using a
      dual AGC model.
AB  - An analog inner hair cell and auditory nerve circuit using a dual AGC model has
      been implemented using 0.35 micron mixed-signal technology. A fully-differential
      current-mode architecture is used and the ability to correct channel mismatch is
      evaluated with matched layouts as well as with digital current tuning. The Meddis
      test paradigm is used to examine the analog implementation's auditory processing
      capabilities and investigate the circuit's ability to correct DC mismatch. The
      correction techniques used demonstrate the analog inner hair cell and auditory
      nerve circuit's potential use in low-power, multiple-sensor analog biomimetic
      systems with highly reproducible signal processing blocks on a single massively
      parallel integrated circuit. 

PMID- 24875285
TI  - A configurable and low-power mixed signal SoC for portable ECG monitoring
      applications.
AB  - This paper describes a mixed-signal ECG System-on-Chip (SoC) that is capable of
      implementing configurable functionality with low-power consumption for portable
      ECG monitoring applications. A low-voltage and high performance analog front-end
      extracts 3-channel ECG signals and single channel electrode-tissue-impedance
      (ETI) measurement with high signal quality. This can be used to evaluate the
      quality of the ECG measurement and to filter motion artifacts. A custom digital
      signal processor consisting of 4-way SIMD processor provides the configurability
      and advanced functionality like motion artifact removal and R peak detection. A
      built-in 12-bit analog-to-digital converter (ADC) is capable of adaptive sampling
      achieving a compression ratio of up to 7, and loop buffer integration reduces the
      power consumption for on-chip memory access. The SoC is implemented in 0.18 MUm
      CMOS process and consumes 32 MU W from a 1.2 V while heart beat detection
      application is running, and integrated in a wireless ECG monitoring system with
      Bluetooth protocol. Thanks to the ECG SoC, the overall system power consumption
      can be reduced significantly. 

PMID- 24875283
TI  - The ApoE4 genotype modifies the relationship of long-term glycemic control with
      cognitive functioning in elderly with type 2 diabetes.
AB  - AIM: To assess whether the APOE4 genotype affects the relationship of long-term
      glycemic control with cognitive function in elderly with type 2 diabetes (T2D).
      METHODS: Participants were cognitively normal and pertained to a Diabetes
      Registry which provided access to HbA1c levels and other T2D related factors
      since 1998. Glycemic control was defined as the mean of all HbA1c measurements
      available (averaging 18 measurements) per subject. Four cognitive domains
      (episodic memory, semantic categorization, attention/working memory and executive
      function), based on factor analysis and an overall cognitive score (the sum of
      the 4 cognitive domains) were the outcome measures. RESULTS: The analysis
      included 808 subjects; 107 (11.9%) subjects had >=1ApoE4 allele. In ApoE4
      carriers, higher mean HbA1c level was significantly associated with lower scores
      on all cognitive measures except attention/working memory (p-values ranging from
      0.047 to 0.003). In ApoE4 non-carriers, higher mean HbA1c level was significantly
      associated with lower scores on executive function, but not with other cognitive
      measures-despite the larger sample size. Compared to non-carriers, there were
      significantly stronger associations in ApoE4 carriers for overall cognition
      (p=0.02), semantic categorization (p=0.03) and episodic memory (p=0.02), and the
      difference for executive function approached statistical significance (p=0.06).
      CONCLUSION: In this cross-sectional study of cognitively normal T2D subjects,
      higher mean HbA1c levels were generally associated with lower cognitive
      performance in ApoE4 carriers, but not in non-carriers, suggesting that ApoE4
      affects the relationship between long-term glycemic control and cognition, so
      APOE4 carriers may be more vulnerable to the insults of poor glycemic control.

PMID- 24875286
TI  - Real-time machine vision FPGA implementation for microfluidic monitoring on Lab
      on-Chips.
AB  - A machine vision implementation on a field-programmable gate array (FPGA) device
      for real-time microfluidic monitoring on Lab-On-Chips is presented in this paper.
      The machine vision system is designed to follow continuous or plug flows, for
      which the menisci of the fluids are always visible. The system discriminates
      between the front or "head" of the flow and the back or "tail" and is able to
      follow flows with a maximum speed of 20 mm/sec in circular channels of a diameter
      of 200 MUm (corresponding to approx. 60 MUl/sec ). It is designed to be part of a
      complete Point-of-Care system, which will be portable and operate in non-ideal
      laboratory conditions. Thus, it is able to cope with noise due to lighting
      conditions and small LoC displacements during the experiment execution. The
      machine vision system can be used for a variety of LoC devices, without the need
      for fiducial markers (such as redundancy patterns) for its operation. The
      underlying application requirements called for a complete hardware
      implementation. The architecture uses a variety of techniques to improve
      performance and minimize memory access requirements. The system input is 8 bit
      grayscale uncompressed video of up to 1 Mpixel resolution. The system uses an
      operating frequency of 170 Mhz and achieves a computational time of 13.97 ms
      (worst case), which leads to a throughput of 71.6 fps for 1 Mpixel video
      resolution. 

PMID- 24875287
TI  - Noise limits of CMOS current interfaces for biosensors: a review.
AB  - Current sensing readout is one of the most frequent techniques used in biosensing
      due to the charge-transfer phenomena occurring at solid-liquid interfaces. The
      development of novel nanodevices for biosensing determines new challenges for
      electronic interface design based on current sensing, especially when compact and
      efficient arrays need to be organized, such as in recent trends of rapid label
      free electronic detection of DNA synthesis. This paper will review the basic
      noise limitations of current sensing interfaces with particular emphasis on
      integrated CMOS technology. Starting from the basic theory, the paper presents,
      investigates and compares charge-sensitive amplifier architectures used in both
      continuous-time and discrete-time approaches, along with their design trade-offs
      involving noise floor, sensitivity to stray capacitance and bandwidth. The
      ultimate goal of this review is providing analog designers with helpful design
      rules and analytical tools. Also, in order to present a comprehensive overview of
      the state-of-the-art, the most relevant papers recently appeared in the
      literature about this topic are discussed and compared. 

PMID- 24875288
TI  - Compressive sensing of electrocardiogram signals by promoting sparsity on the
      second-order difference and by using dictionary learning.
AB  - A new algorithm for the reconstruction of electrocardiogram (ECG) signals and a
      dictionary learning algorithm for the enhancement of its reconstruction
      performance for a class of signals are proposed. The signal reconstruction
      algorithm is based on minimizing the lp pseudo-norm of the second-order
      difference, called as the lp(2d) pseudo-norm, of the signal. The optimization
      involved is carried out using a sequential conjugate-gradient algorithm. The
      dictionary learning algorithm uses an iterative procedure wherein a signal
      reconstruction and a dictionary update steps are repeated until a convergence
      criterion is satisfied. The signal reconstruction step is implemented by using
      the proposed signal reconstruction algorithm and the dictionary update step is
      implemented by using the linear least-squares method. Extensive simulation
      results demonstrate that the proposed algorithm yields improved reconstruction
      performance for temporally correlated ECG signals relative to the state-of-the
      art lp(1d)-regularized least-squares and Bayesian learning based algorithms. Also
      for a known class of signals, the reconstruction performance of the proposed
      algorithm can be improved by applying it in conjunction with a dictionary
      obtained using the proposed dictionary learning algorithm. 

PMID- 24875289
TI  - Redefining self: patients' decision making about treatment for multiple
      sclerosis.
AB  - The treatment of multiple sclerosis (MS) has become possible with the advent of
      disease-modifying therapies, but little is known about patients' experiences when
      faced with a complex array of treatment options. The purpose of this
      phenomenological study was to explore the lived experience of making a first
      decision about treatment with disease-modifying therapies for relapsing-remitting
      MS. Nine participants shared their perspectives on negotiating the decision to
      accept, refuse, or delay treatment. All individuals described a core theme in
      which decision making about treatment was part of a process of coming to a
      "redefined self." This core theme included reflections about self-image, quality
      of life, goals, and being a person with MS. Six common themes supporting this
      core theme were (a) weighing and deciding what's important, (b) acknowledging the
      illness as part of oneself, (c) playing the mental game, (d) seeking credible
      resources, (e) evaluating symptoms and fit with quality of life, and (f) managing
      the roles and involvement of family. The findings of this study provide a greater
      understanding about the experience of making a therapeutic choice for those with
      MS and offer insights for nurses when supporting patients faced with options
      about treatment. 

PMID- 24875290
TI  - Peripheral immune response and infection in first-time and recurrent ischemic
      stroke or transient ischemic attack.
AB  - GOALS: The aims of this study were to determine if the infection rate differs
      between the first and recurrent ischemic stroke/transient ischemic attack (TIA),
      if the pattern of the peripheral immune response (PIR) differs between the first
      and recurrent ischemic stroke/TIA and if infection further influenced the pattern
      of the PIR. METHODS: Retrospective review of 500 stroke cases with strict
      exclusion criteria (e.g., hemorrhagic stroke, subarachnoid hemorrhage, or
      spontaneous intracerebral hemorrhage; history of cancer; on steroids or immune
      suppressive drugs; recent invasive procedure) resulted in inclusion of 198 cases.
      Independent variables were first stroke or recurrent stroke and not infected or
      infected cases. Main-effect dependent variables were the white blood cell (WBC)
      and differential leukocyte counts (percentages of 100 cell counts for
      neutrophils, lymphocytes, and monocytes and absolute counts of neutrophils,
      lymphocytes, and monocytes). FINDINGS: Infection rate was not different between
      the first versus recurrent stroke (p = .279). The pattern of WBC and differential
      counts were not different between groups, but addition of the covariate of
      infection showed group differences (p = .05). A four-group comparison of the
      dependent variables with the laboratory normal ranges showed lymphocyte
      percentages below the lower range limit in all four groups. Generalized linear
      modeling showed a modest rise (15%) in WBC counts in both groups with concomitant
      infection, a modestly low (-18%) lymphocyte percentage in recurrent stroke with
      infection, and a more substantial rise (22%-26%) in absolute neutrophil count in
      both groups with concomitant infection. CONCLUSIONS: Infection influences the
      pattern of the PIR in the first and recurrent stroke/TIA, and this difference can
      be quantified.

PMID- 24875291
TI  - Effect of panel shape of soccer ball on its flight characteristics.
AB  - Soccer balls are typically constructed from 32 pentagonal and hexagonal panels.
      Recently, however, newer balls named Cafusa, Teamgeist 2, and Jabulani were
      respectively produced from 32, 14, and 8 panels with shapes and designs
      dramatically different from those of conventional balls. The newest type of ball,
      named Brazuca, was produced from six panels and will be used in the 2014 FIFA
      World Cup in Brazil. There have, however, been few studies on the aerodynamic
      properties of balls constructed from different numbers and shapes of panels.
      Hence, we used wind tunnel tests and a kick-robot to examine the relationship
      between the panel shape and orientation of modern soccer balls and their
      aerodynamic and flight characteristics. We observed a correlation between the
      wind tunnel test results and the actual ball trajectories, and also clarified how
      the panel characteristics affected the flight of the ball, which enabled
      prediction of the trajectory. 

PMID- 24875292
TI  - Quantification of eggshell microstructure using X-ray micro computed tomography.
AB  - 1. X-ray microcomputed tomography can be used to produce rapid, fully analysable,
      three-dimensional images of biological and other materials without the need for
      complex or tedious sample preparation and sectioning. We describe the use of this
      technique to visualise and analyse the microstructure of fragments of shell taken
      from three regions of chicken eggs (sharp pole, blunt pole and equatorial
      region). 2. Two- and three-dimensional images and data were obtained at a
      resolution of 1.5 microns. The images were analysed to provide measurements of
      shell thickness, the spacial density of mammillary bodies, the frequency, shape,
      volume and effective diameter of individual pore spaces, and the intrinsic
      sponginess (proportion of non-X-ray dense material formed by vesicles) of the
      shell matrix. Measurements of these parameters were comparable with those derived
      by traditional methods and reported in the literature. 3. The advantages of using
      this technology for the quantification of eggshell microstructural parameters and
      its potential application for commercial, research and other purposes are
      discussed.

PMID- 24875293
TI  - Metabolic syndrome reduces bone mineral density in overweight adolescents.
AB  - Growing concern has focused on the occurrence of metabolic syndrome (MetS) and
      its effects on bone mass. There is little information available in the literature
      concerning the relationship between MetS and BMD in adolescents. The aim of this
      study was to evaluate the effects of MetS and its components on bone mineral
      density (BMD) in overweight adolescent boys and girls. This cross-sectional study
      assessed 271 overweight adolescents with or without MetS (age 10 to 16years).
      Anthropometric and biochemical tests were performed. Lumbar spine, proximal femur
      and total and subtotal body BMD values were obtained by bone densitometry with
      dual-energy X-ray absorptiometry. MetS was observed in 14% of the adolescents.
      Overweight adolescents of both genders who were positive for MetS presented with
      significant decreases in BMD (g/cm(2)/kg bodyweight) at all sites evaluated
      (p<0.01). Female adolescents with large waist circumference, low HDLc,
      hypertriglyceridemia and high blood pressure showed significant reductions in BMD
      at all sites evaluated (p<0.01) and, with the exception of increased
      triglycerides (which had no effect on BMD, p>0.05), the same pattern was observed
      in male adolescents. Linear regression analyses revealed that waist circumference
      was negatively correlated with BMD in both genders and that triglycerides were
      negatively correlated with BMD only in female adolescents. Our results suggest
      that overweight adolescents with MetS have lower BMD than adolescents without
      MetS. Among all MetS components measured, increased waist circumference had the
      strongest relationship with reductions in BMD. 

PMID- 24875295
TI  - Structural order in ultrathin films of the monolayer protected clusters based
      upon 4 nm gold nanocrystals: an experimental and theoretical study.
AB  - The structural order in ultrathin films of monolayer protected clusters (MPCs) is
      important in a number of application areas but can be difficult to demonstrate by
      conventional methods, particularly when the metallic core dimension, d, is in the
      intermediate size-range, 1.5 < d < 5.0 nm. Here, improved techniques for the
      synthesis of monodisperse thiolate-protected gold nanoparticles have made
      possible the production of dodecane-thiolate saturated ~4 +/- 0.5 nm Au clusters
      with single-crystal core structure and morphology. An ultrathin ordered film or
      superlattice of these nanocrystal-core MPCs is prepared and investigated using
      aberration corrected scanning/transmission electron microscopy (STEM) which
      allowed imaging of long-range hexagonally ordered superlattices of the
      nanocrystals, separated by the thiolate groups. The lattice constants determined
      by direct imaging are in good agreement with those determined by small-angle
      electron diffraction. The STEM image revealed the characteristic grain boundary
      (GB) with sigma (Sigma) 13 in the interface between two crystals. The formation
      and structures found are interpreted on the basis of theoretical calculations
      employing molecular dynamics (MD) simulations and coarse-grained (CG) approach. 

PMID- 24875296
TI  - C-kit overexpression is not associated with KIT gene mutations in chromophobe
      renal cell carcinoma or renal oncocytoma.
AB  - INTRODUCTION: C-kit overexpression has previously been described in chromophobe
      renal cell carcinoma (cpRCC) and renal oncocytoma (RO). However, so far no KIT
      mutations have been found. The objective of our study was to analyse c-kit in a
      large cohort of renal tumors and to perform KIT mutation analysis in a subset
      cpRCC and RO cases with overexpression of c-kit. MATERIALS AND METHODS: We
      studied the immunohistochemical expression of c-kit on tissue microarrays
      containing formalin-fixed, paraffin-embedded samples of 948 patients with renal
      tumors. CpRCC and RO cases with c-kit overexpression (n=23) were analyzed for KIT
      mutations in exons 9, 11, 13, 14, 15, and 17. RESULTS: Expression of c-kit was
      found in 6/642 (0.9%) clear cell RCC, 3/154 (1.9%) papillary RCC, 54/69 (78.3%)
      cpRCC, 37/45 (82.2%) RO and 2/30 (6.7%) of other unclassified tumor types. In
      none of the RO and cpRCC cases analyzed, a KIT gene mutation was found.
      CONCLUSION: C-kit expression is found in the majority of cpRCC and RO, but these
      tumors do not harbor the usual c-kit activating mutations. This may have
      implications for the use of tyrosine kinase inhibitors in patients with advanced
      cpRCC and c-kit expression.

PMID- 24875294
TI  - SHP2 regulates chondrocyte terminal differentiation, growth plate architecture
      and skeletal cell fates.
AB  - Loss of PTPN11/SHP2 in mice or in human metachondromatosis (MC) patients causes
      benign cartilage tumors on the bone surface (exostoses) and within bones
      (enchondromas). To elucidate the mechanisms underlying cartilage tumor formation,
      we investigated the role of SHP2 in the specification, maturation and
      organization of chondrocytes. Firstly, we studied chondrocyte maturation by
      performing RNA-seq on primary chondrocyte pellet cultures. We found that SHP2
      depletion, or inhibition of the ERK1/2 pathway, delays the terminal
      differentiation of chondrocytes from the early-hypertrophic to the late
      hypertrophic stage. Secondly, we studied chondrocyte maturation and organization
      in mice with a mosaic postnatal inactivation of Ptpn11 in chondrocytes. We found
      that the vertebral growth plates of these mice have expanded domains of early
      hypertrophic chondrocytes that have not yet terminally differentiated, and their
      enchondroma-like lesions arise from chondrocytes displaced from the growth plate
      due to a disruption in the organization of maturation and ossification zones.
      Furthermore, we observed that lesions from human MC patients also display
      disorganized chondrocyte maturation zones. Next, we found that inactivation of
      Ptpn11 in Fsp1-Cre-expressing fibroblasts induces exostosis-like outgrowths,
      suggesting that loss of SHP2 in cells on the bone surface and at bone-ligament
      attachment sites induces ectopic chondrogenesis. Finally, we performed lineage
      tracing to show that exostoses and enchondromas in mice likely contain mixtures
      of wild-type and SHP2-deficient chondrocytes. Together, these data indicate that
      in patients with MC, who are heterozygous for inherited PTPN11 loss-of-function
      mutations, second-hit mutations in PTPN11 can induce enchondromas by disrupting
      the organization and delaying the terminal differentiation of growth plate
      chondrocytes, and can induce exostoses by causing ectopic chondrogenesis of cells
      on the bone surface. Furthermore, the data are consistent with paracrine
      signaling from SHP2-deficient cells causing SHP2-sufficient cells to be
      incorporated into the lesions.

PMID- 24875297
TI  - Immunohistochemical localization of steroid receptor coactivators in
      chondrosarcoma: an in vivo tissue microarray study.
AB  - Chondrosarcoma is the second most common type of primary bone malignancy
      following up osteosarcoma, characterized by resistance to conventional
      chemotherapeutic agents and radiation regimens. The p160 family members steroid
      receptor coactivator-1 and -3 (SRC-1 and SRC-3) have been implied in the
      regulation of cancer growth, migration, invasion, metastasis and chemotherapeutic
      resistance; but we still lack detailed information about the levels of SRCs in
      chondrosarcoma. In this study, expression of SRC-1 and SRC-3 in chondrosarcoma
      was examined by immunohistochemistry with tissue microarrays; the four score
      system (0, 1, 2 and 3) was used to evaluate the staining. The results showed that
      there were no gender-, site- or age-differences regarding the expression of SRC-1
      or SRC-3 (p>0.05); organ (bone or cartilage) -differences were only detected for
      SRC-1 but not SRC-3 (p<0.05). Significant higher levels of SRC-1 and SRC-3 were
      detected in MDC and PDC when compared to WDC. Our study clearly demonstrated
      differentiation-dependant expression of SRC-1 and SRC-3 in chondrosarcoma, may be
      novel targets for the prognosis and/or treatment of chondrosarcoma, would have
      opened a new avenue and established foundation for studying chondrosarcoma. 

PMID- 24875299
TI  - Translational research is a key to nongeneticist physicians' genomics education.

PMID- 24875298
TI  - Targeted next-generation sequencing of deafness genes in hearing-impaired
      individuals uncovers informative mutations.
AB  - PURPOSE: Targeted next-generation sequencing provides a remarkable opportunity to
      identify variants in known disease genes, particularly in extremely heterogeneous
      disorders such as nonsyndromic hearing loss. The present study attempts to shed
      light on the complexity of hearing impairment. METHODS: Using one of two next
      generation sequencing panels containing either 80 or 129 deafness genes, we
      screened 30 individuals with nonsyndromic hearing loss (from 23 unrelated
      families) and analyzed 9 normal-hearing controls. RESULTS: Overall, we found an
      average of 3.7 variants (in 80 genes) with deleterious prediction outcome,
      including a number of novel variants, in individuals with nonsyndromic hearing
      loss and 1.4 in controls. By next-generation sequencing alone, 12 of 23 (52%)
      probands were diagnosed with monogenic forms of nonsyndromic hearing loss; one
      individual displayed a DNA sequence mutation together with a microdeletion. Two
      (9%) probands have Usher syndrome. In the undiagnosed individuals (10/23; 43%) we
      detected a significant enrichment of potentially pathogenic variants as compared
      to controls. CONCLUSION: Next-generation sequencing combined with microarrays
      provides the diagnosis for approximately half of the GJB2 mutation-negative
      individuals. Usher syndrome was found to be more frequent in the study cohort
      than anticipated. The conditions in a proportion of individuals with nonsyndromic
      hearing loss, particularly in the undiagnosed group, may have been caused or
      modified by an accumulation of unfavorable variants across multiple genes.

PMID- 24875300
TI  - Ethnic effect on FMR1 carrier rate and AGG repeat interruptions among Ashkenazi
      women.
AB  - PURPOSE: Fragile X syndrome, a common cause of intellectual disability, is
      usually caused by CGG trinucleotide expansion in the FMR1 gene. CGG repeat size
      correlates with expansion risk. Premutation alleles (55-200 repeats) may expand
      to full mutations in female meiosis. Interspersed AGG repeats decrease allele
      instability and expansion risk. The carrier rate and stability of FMR1 alleles
      were evaluated in large cohorts of Ashkenazi and non-Ashkenazi women. METHODS: A
      total of 4,344 Ashkenazi and 4,985 non-Ashkenazi cases were analyzed using
      Southern blotting and polymerase chain reaction between 2004 and 2011. In
      addition, AGG interruptions were evaluated in 326 Ashkenazi and 298 non-Ashkenazi
      women who were recruited during 2011. RESULTS: Both groups had major peaks of 30
      and 29 repeats. Ashkenazi women had a higher frequency of 30 repeats and a lower
      frequency of other peaks (P < 0.0001). A higher rate of premutations in the 55-59
      repeats range (1:114 vs. 1:277) was detected among the Ashkenazi women. Loss of
      AGG interruptions (<2) was significantly less common among Ashkenazi women (9 vs.
      19.5% for non-Ashkenazi women, P = 0.0002). CONCLUSION: Ashkenazi women have a
      high fragile X syndrome carrier rate and mostly lower-range premutations, and
      carry a low risk for expansion to a full mutation. Normal-sized alleles in
      Ashkenazi women have higher average number of AGG interruptions that may increase
      stability. These factors may decrease the risk for fragile X syndrome offspring
      among Ashkenazi women.

PMID- 24875302
TI  - How do research participants perceive "uncertainty" in genome sequencing?
AB  - PURPOSE: The scope of uncertainty in genome sequence information has no rival in
      health-care delivery. We present data from adults participating in a National
      Institutes of Health study using this technology, in which perceptions of
      uncertainty are hypothesized to be key in predicting decisions to learn and act
      on genome health information. METHODS: We conducted six professionally moderated
      focus groups with 39 randomly selected ClinSeq participants varying on whether
      they had coronary heart disease and had received prior sequence results. We
      elicited perceptions of the uncertainties associated with genome sequencing using
      written prompts. RESULTS: Participants perceived uncertainty as a quality of
      genome information. The majority of participants characterized uncertainty of
      sequencing information as "changing, fluid, developing, or ground breaking."
      These responses led to anticipation of more optimistic future outcomes. Fewer
      participants described uncertainty as "questionable, less accurate, limited, or
      poorly understood." These perceptions seemed to undermine participants' faith in
      genome information, leading to feelings of disillusionment. CONCLUSION: Our
      findings suggest that perceptions of uncertainty are related to epistemological
      beliefs that inform expectations for the information. Interventions that promote
      realistic expectations of genome sequencing may mitigate negative responses to
      uncertainty.

PMID- 24875304
TI  - Serious Fraud Office launches criminal inquiry into GlaxoSmithKline.

PMID- 24875303
TI  - The UK abortion anomaly that can no longer be ignored.

PMID- 24875301
TI  - Postanalytical tools improve performance of newborn screening by tandem mass
      spectrometry.
AB  - PURPOSE: The purpose of this study was to compare performance metrics of
      postanalytical interpretive tools of the Region 4 Stork collaborative project to
      the actual outcome based on cutoff values for amino acids and acylcarnitines
      selected by the California newborn screening program. METHODS: This study was a
      retrospective review of the outcome of 176,186 subjects born in California
      between 1 January and 30 June 2012. Raw data were uploaded to the Region 4 Stork
      Web portal as .csv files to calculate tool scores for 48 conditions
      simultaneously using a previously unpublished functionality, the tool runner.
      Scores for individual target conditions were deemed informative when equal or
      greater to the value representing the first percentile rank of known true
      positive cases (17,099 cases in total). RESULTS: In the study period, the actual
      false-positive rate and positive predictive value were 0.26 and 10%,
      respectively. Utilization of the Region 4 Stork tools, simple interpretation
      rules, and second-tier tests could have achieved a false-positive rate as low as
      0.02% and a positive predictive value >50% by replacing the cutoff system with
      Region 4 Stork tools as the primary method for postanalytical interpretation.
      CONCLUSION: Region 4 Stork interpretive tools, second-tier tests, and other
      evidence-based interpretation rules could have reduced false-positive cases by up
      to 90% in California.

PMID- 24875305
TI  - Computational comparison of mediated current generation capacity of Chlamydomonas
      reinhardtii in photosynthetic and respiratory growth modes.
AB  - Chlamydomonas reinhardtii possesses many potential advantages to be exploited as
      a biocatalyst in microbial fuel cells (MFCs) for electricity generation. In the
      present study, we performed computational studies based on flux balance analysis
      (FBA) to probe the maximum potential of C. reinhardtii for current output and
      identify the metabolic mechanisms supporting a high current generation in three
      different cultivation conditions, i.e., heterotrophic, photoautotrophic and
      mixotrophic growth. The results showed that flux balance limitations allow the
      highest current output for C. reinhardtii in the mixotrophic growth mode (2.368
      A/gDW), followed by heterotrophic growth (1.141 A/gDW) and photoautotrophic
      growth the lowest (0.7035 A/gDW). The significantly higher mediated electron
      transfer (MET) rate in the mixotrophic mode is in complete contrast to previous
      findings for a photosynthetic cyanobacterium, and was attributed to the fact that
      for C. reinhardtii the photophosphorylation improved the efficiency of converting
      the acetate into biomass and NADH production. Overall, the cytosolic NADH
      dependent current production was mainly associated with five reactions in both
      mixotrophic and photoautotrophic nutritional modes, whereas four reactions
      participated in the heterotrophic mode. The mixotrophic and photoautotrophic
      metabolisms were alike and shared the same set of reactions for maximizing
      current production, whereas in the heterotrophic mode, the current production was
      additionally contributed by the metabolic activities in the two organelles:
      glyoxysome and chloroplast. In conclusion, C. reinhardtii has a potential to be
      exploited in MFCs of MET mode to produce a high current output. 

PMID- 24875307
TI  - Heavy metals and polycyclic aromatic hydrocarbons in sediments from the Shenzhen
      River, South China.
AB  - With the analysis of eight heavy metals (As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn) and
      sixteen polycyclic aromatic hydrocarbons (PAHs) in sediments from the Shenzhen
      River, South China, the ecological risks associated were evaluated using
      Hakanson's method (for the metals) and the Effect Range Low/Effect Range Median
      (ERL/ERM) method (for the PAHs). The result shows concentrations of heavy metal
      in the order Zn > Cu > Cr > Ni > Pb > As > Cd > Hg, and among which the Zn, Cu,
      Ni, and Pb are exceeding the maximum contaminant level for sediments while those
      of PAHs are far below. The potential ecological risk index value for the heavy
      metals in the sediment samples was 261.90, which is in the moderate risk
      category. Total PAH concentrations in the sediments ranged from 1,028 to 1,120
      ng/g, which are all far lower than the sediment guideline concentration of 4,022
      ng/g, indicating that the risks of biological impacts caused by PAHs in Shenzhen
      River sediments are, therefore, relatively low. Besides, the fluorene
      concentration was above the ERL, and would potentially cause negative biological
      effects in the Shenzhen River. Heavy metals risks are suggested among the most
      important concerns that the environmental recover measures pay attention to.

PMID- 24875308
TI  - The effect of spent bleaching earth ageing process on its physicochemical and
      microbial composition and its potential use as a source of fatty acids and
      triterpenes.
AB  - This study was aimed at investigating the physicochemical and microbiological
      changes that took place during the ageing process of spent bleaching earth in the
      presence of autochthonous microorganisms. Research material included fresh spent
      bleaching earth (SBE0) and the same material after 3 years of storage at the
      constant temperature of 20  degrees C, without aeration and moistening (SBE3).
      Changes in the chemical composition of analysed waste material were observed
      during its ageing process point to a spontaneous bioconversion of fat substance
      towards formation and/or release of free saturated fatty acids C16:0 and C18:0
      (14.3 g 100 g(-1) D.M.), triterpenes (8.48 g 100 g(-1) D.M.), cholesterol (3.29 g
      100 g(-1) D.M.), small quantities of carbohydrates and esters (0.80 g 100 g(-1)
      D.M.). This process was accompanied by other changes in physicochemical
      parameters of the waste material, such as colour, odour and viscosity, decrease
      in fat content from 28.27 to 24.6 % and that of soluble forms of metals (Mo, Cu,
      Fe, Zn, Ni, Cr and Mn), ranging from 25 to 75 %, and an increase in pH, from 3.85
      to 4.2. At the same time, changes in the microbial consortium were observed.

PMID- 24875306
TI  - Inaccurate ascertainment of morbidity and mortality due to influenza in
      administrative databases: a population-based record linkage study.
AB  - BACKGROUND: Historically, counting influenza recorded in administrative health
      outcome databases has been considered insufficient to estimate influenza
      attributable morbidity and mortality in populations. We used database record
      linkage to evaluate whether modern databases have similar limitations. METHODS:
      Person-level records were linked across databases of laboratory notified
      influenza, emergency department (ED) presentations, hospital admissions and death
      registrations, from the population (~6.9 million) of New South Wales (NSW),
      Australia, 2005 to 2008. RESULTS: There were 2568 virologically diagnosed
      influenza infections notified. Among those, 25% of 40 who died, 49% of 1451 with
      a hospital admission and 7% of 1742 with an ED presentation had influenza
      recorded on the respective database record. Compared with persons aged >=65 years
      and residents of regional and remote areas, respectively, children and residents
      of major cities were more likely to have influenza coded on their admission
      record. Compared with older persons and admitted patients, respectively, working
      age persons and non-admitted persons were more likely to have influenza coded on
      their ED record. On both ED and admission records, persons with influenza type A
      infection were more likely than those with type B infection to have influenza
      coded. Among death registrations, hospital admissions and ED presentations with
      influenza recorded as a cause of illness, 15%, 28% and 1.4%, respectively, also
      had laboratory notified influenza. Time trends in counts of influenza recorded on
      the ED, admission and death databases reflected the trend in counts of
      virologically diagnosed influenza. CONCLUSIONS: A minority of the death, hospital
      admission and ED records for persons with a virologically diagnosed influenza
      infection identified influenza as a cause of illness. Few database records with
      influenza recorded as a cause had laboratory confirmation. The databases have
      limited value for estimating incidence of influenza outcomes, but can be used for
      monitoring variation in incidence over time.

PMID- 24875309
TI  - Mercury accumulation and tissue-specific antioxidant efficiency in the wild
      European sea bass (Dicentrarchus labrax) with emphasis on seasonality.
AB  - The main goal of this study was to assess both mercury (Hg) accumulation and
      organs' specific oxidative stress responses of gills, liver and kidney of
      Dicentrarchus labrax with emphasis on seasonality. Fish were collected in cold
      and warm periods in three stations: reference, moderated and highly contaminated
      sites. Our results showed that seasonal factors slightly influenced Hg
      accumulation between year periods (cold and warm) and strongly affected organs'
      response basal levels. In contrast, seasonality seemed not to influence oxidative
      stress responses, since similar response patterns were obtained for both year
      periods, and moderate degree of antioxidant responses was obtained. Moreover, the
      oxidative stress profile may be attributed to Hg contamination degree, which
      showed organ-specific response and accumulation patterns. Hence, gills showed to
      be able to adapt to Hg contamination, and in opposition, kidney and liver
      demonstrated some vulnerability to Hg toxicity. The critical Hg concentrations
      indicated specific threshold limits for each organ. Overall, seasonality should
      be taken into account in monitoring programmes, helping to characterize the
      individuals' reference values of response and thus to discriminate between the
      effects induced by natural causes or by contamination. 

PMID- 24875310
TI  - Microbial diversity in innovative mesophilic/thermophilic temperature-phased
      anaerobic digestion of sludge.
AB  - Anaerobic digestion (AD) is one of the few sustainable technologies that both
      produce energy and treat waste streams. Driven by a complex and diverse community
      of microbes, AD may be affected by different factors, many of which also
      influence the composition and activity of the microbial community. In this study,
      the biodiversity of microbial populations in innovative mesophilic/thermophilic
      temperature-phased AD of sludge was evaluated by means of fluorescence in situ
      hybridization (FISH). The increase of digestion temperature drastically affected
      the microbial composition and selected specialized biomass. Hydrogenotrophic
      Methanobacteriales and the protein fermentative bacterium Coprothermobacter spp.
      were identified in the thermophilic anaerobic biomass. Shannon-Weaver diversity
      (H') and evenness (E) indices were calculated using FISH data. Species richness
      was lower under thermophilic conditions compared with the values estimated in
      mesophilic samples, and it was flanked by similar trend of the evenness
      indicating that thermophilic communities may be therefore more susceptible to
      sudden changes and less prompt to adapting to operative variations. 

PMID- 24875311
TI  - Antifungal efficiency assessment of the TiO2 coating on facade paints.
AB  - The work studies the photocatalytic activity and the antifungal efficiency of the
      TiO2/Zn-Al coatings placed on the target commercial facade paints. The
      photocatalytic active nanocomposite based on TiO2 and Zn-Al-layered double
      hydroxides (ZnAl-LDHs) was synthesized by a wet impregnation technique with 3 %
      w/w TiO2. The freshly prepared suspension was applied by spray technique on the
      surfaces of the white facade paints. The goal of the work was to develop a method
      that quickly quantifies the antifungal activity of the commercial facade paints
      with and without biocidal components covered with a photocatalytic coating. The
      essence of the proposed method is the monitoring of the fungal growth (artificial
      ageing conditions) and the quantification of its development (UV-A 0.13 mWcm(-2))
      on the facade paint surfaces. A special fungus nutrient (potato dextrose agar
      (PDA)) was inoculated with the spores of the Aspergillus niger ATCC 6275, and the
      test samples (facade paints with and without photocatalytic coating) were placed
      on the inoculated nutrient in the petri dishes. The images of the fungal growth
      on the samples of the facade paints, during a period of 5 days, were imported
      into Matlab R2012a where they were converted to binary images (BW), based on the
      adequate threshold. The percentage of the surface coverage was calculated by
      applying the specifically written program code which determines the ratio of the
      black and white pixels. The black pixels correspond to the surface covered with
      hyphae and mycelia of the fungus.

PMID- 24875313
TI  - Physicochemical and morphological properties of plasticized poly(vinyl alcohol)
      agar biodegradable films.
AB  - The effects of the addition of glycerol (GLY) on the physicochemical and
      morphological properties of poly(vinyl alcohol) (PVA)-agar films were reported.
      PVA-agar films were prepared by solution cast method, and the addition of GLY in
      PVA-agar films altered the optical properties, resulting in a decrease in opacity
      values and in the color difference (DeltaE) of the films. Structural
      characterization using Fourier transformation infrared (FTIR) spectroscopy and X
      ray diffraction (XRD) indicated that the presence of GLY altered the intensity of
      the bands (from 1200 to 800cm(-1)) and crystallinity. The characterization of the
      thermal properties indicated that an increase in the agar content produces a
      decrease in the melting temperature and augments the heat of fusion. Similar
      tendencies were observed in plasticized films, but at different magnification.
      The formulation that demonstrated the lowest mechanical properties contained
      25wt.% agar, whereas the formulation that contained 75wt.% agar demonstrated a
      significant improvement. The water vapor transmission rate (WVTR) and surface
      morphology analysis demonstrated that the structure of PVA-agar films is
      reorganized upon GLY addition. The physicochemical properties of PVA-agar films
      using GLY as a plasticizer provide information for the application of this
      formulation as packaging material for specific food applications. 

PMID- 24875315
TI  - Characterization and cDNA sequence of Bothriechis schlegeliil-amino acid oxidase
      with antibacterial activity.
AB  - Snake venoms are complex mixtures of proteins including l-amino acid oxidase
      (lAAO). A lAAO (named BslAAO) with a mass of 56kDa and a theoretical Ip of 5.79,
      was purified from Bothriechis schlegelii venom through size-exclusion, ion
      exchange and affinity chromatography. The entire protein sequence of 498 amino
      acids, was determined from cDNA using reverse-transcribed mRNA isolated from
      venom gland. The enzyme showed dose-dependent inhibition of bacterial growth.
      BslAAO showed inhibitory effect against S. aureus with a MIC of 4MUg/mL and a MBC
      of 8MUg/mL. Against Acinetobacter baumannii, showed a MIC of 2MUg/mL and MBC of
      4MUg/mL, No effect was observed in Escherichia coli. This antibacterial activity
      was inhibited by catalase, indicating that antimicrobial activity was due to H2O2
      production. BslAAO did not show any cytotoxic activity toward mouse myoblast cell
      line C2C12 or peripheral blood mononuclear cells. The enzyme oxidated l-Leu, with
      a Km of 16.37MUM and a Vmax of 0.39MUM/min. Snake venoms lAAOs, are potential
      frames of different therapeutics molecules since these enzymes exhibit low MICs
      and MBCs and show to be harmless to human cells due to microorganisms being
      generally several fold more sensitive to reactive oxygen species than human
      tissues. 

PMID- 24875312
TI  - Exposure to multiple parasites is associated with the prevalence of active
      convulsive epilepsy in sub-Saharan Africa.
AB  - BACKGROUND: Epilepsy is common in developing countries, and it is often
      associated with parasitic infections. We investigated the relationship between
      exposure to parasitic infections, particularly multiple infections and active
      convulsive epilepsy (ACE), in five sites across sub-Saharan Africa. METHODS AND
      FINDINGS: A case-control design that matched on age and location was used. Blood
      samples were collected from 986 prevalent cases and 1,313 age-matched community
      controls and tested for presence of antibodies to Onchocerca volvulus, Toxocara
      canis, Toxoplasma gondii, Plasmodium falciparum, Taenia solium and HIV. Exposure
      (seropositivity) to Onchocerca volvulus (OR = 1.98; 95%CI: 1.52-2.58, p<0.001),
      Toxocara canis (OR = 1.52; 95%CI: 1.23-1.87, p<0.001), Toxoplasma gondii (OR =
      1.28; 95%CI: 1.04-1.56, p = 0.018) and higher antibody levels (top tertile) to
      Toxocara canis (OR = 1.70; 95%CI: 1.30-2.24, p<0.001) were associated with an
      increased prevalence of ACE. Exposure to multiple infections was common (73.8% of
      cases and 65.5% of controls had been exposed to two or more infections), and for
      T. gondii and O. volvulus co-infection, their combined effect on the prevalence
      of ACE, as determined by the relative excess risk due to interaction (RERI), was
      more than additive (T. gondii and O. volvulus, RERI = 1.19). The prevalence of T.
      solium antibodies was low (2.8% of cases and 2.2% of controls) and was not
      associated with ACE in the study areas. CONCLUSION: This study investigates how
      the degree of exposure to parasites and multiple parasitic infections are
      associated with ACE and may explain conflicting results obtained when only
      seropositivity is considered. The findings from this study should be further
      validated.

PMID- 24875317
TI  - Influence of the acid type in the production of chitosan films reinforced with
      bacterial nanocellulose.
AB  - Chitosan films reinforced with bacterial cellulose (BC) nanoribbons were studied
      to understand the influence of acid (acetic and lactic acids) on the reinforcing
      effect. For both acids, the maximum concentration of the reinforcing constituent
      was 5wt% with respect to the dry weight of chitosan. The infrared spectra,
      mechanical properties, morphology and antimicrobial activity of the films were
      analyzed. The results showed a difference between the acids in their behavior and
      effect on the reinforcement, with a tensile strength of 12.3MPa for the acetic
      acid films and 3.3MPa for the lactic acid films. Additionally, the bacterial
      inhibition tests were shown to be positive for the lactic acid films and negative
      for the acetic acid films. Therefore, exchanging the acid used in these films may
      be desirable for certain applications. 

PMID- 24875316
TI  - Characterization and pharmacodynamic properties of Arnica montana complex.
AB  - A dark brown polymeric complex was isolated from flowering parts of medicinal
      plant Arnica montana L. by hot alkaline extraction followed by neutralization and
      multi-step extractions with organic solvents. It was recovered in 5.7% yield, on
      GPC showed two peaks of molecular mass of 9 and 3.5kDa. The compositional
      analyses of Arnica complex revealed the presence of carbohydrates (26%), uronic
      acids (12%), phenolics (1.25mM or 213mg of GAE/1g), and low protein content
      (~1%). The carbohydrate moiety was rich mainly in rhamnogalacturonan and
      arabinogalactan. The antitussive tests showed the reduction of the cough efforts
      by Arnica complex, however, its total antitussive effect was lower compared with
      that of codeine, the strongest antitussive agent. The bronchodilatory activity of
      Arnica complex was similar to salbutamol, a classic antiasthmatic drug, and was
      confirmed by significantly decreased values of specific airways resistance in
      vivo and by considerably attenuated the amplitude of acetylcholine and histamine
      induced contractions in vitro. Arnica complex did not show any cytotoxic effect
      on mouse fibroblast cultures and human lung cells, up to the dose of 500MUg/mL. 

PMID- 24875314
TI  - Radiation degradation of (1->3)-beta-d-glucan from yeast with a potential
      application as a plant growth promoter.
AB  - The (1->3)-beta-d-glucan extracted from the yeast cell wall was irradiated by
      gamma-rays from a Co-60 source at dose range of 100-300kGy in a swelling
      condition of 10, 15 and 20% for degradation. The water-soluble contents of
      irradiated samples obtained by 10% (1->3)-beta-d-glucan mixture increased from
      25.89 to 66.71% by the increasing of irradiation doses from 100 to 300kGy. While
      the molecular weight of the water-soluble (1->3)-beta-d-glucan was found to be
      decreased from 48.13 to 10.77kDa. In the UV-spectra of irradiated water-soluble
      (1->3)-beta-d-glucan, a new peak appeared at 265nm with the intensity increased
      by the increase of the dose. The IR spectra of irradiated (1->3)-beta-d-glucan
      were recognized by a decrease of the peak intensity at 1156cm(-1) indicated to
      COC glycosidic linkages with the increasing of irradiation dose. In addition,
      radiation degraded (1->3)-beta-d-glucan with Mw about 18kDa prepared at the dose
      of 250kGy displayed a strongly promotion effect on the growth of mustard green
      and the optimum concentration of the degraded (1->3)-beta-d-glucan was found to
      be about 75mgl(-1). Thus, the degraded (1->3)-beta-d-glucan prepared by radiation
      technique displayed as a promising, safety and high effective plant growth
      promoter for agriculture application. 

PMID- 24875319
TI  - Physicochemical characteristics and antioxidant activity of Prunus cerasoides D.
      Don gum exudates.
AB  - The physicochemical properties and antioxidant activity of Prunus cerasoides D.
      Don gum exudates was investigated in this study. The total carbohydrate and
      protein content were found to be 73.72+/-2.44% and 2.33+/-1.25%, respectively.
      Analysis of monosaccharide composition by HPLC-RI system after acid hydrolysis of
      the gum showed the presence of arabinose, galactose, glucose, rhamnose and
      xylose. The molecular weight of the gum was also found to be 5.55*10(5)Da. FTIR
      and DSC studies showed characteristics typical of a natural polysaccharide. The
      viscosity of 2% aqueous solution of the gum exhibited non-Newtonian type of flow
      and the gum was also found to show pH dependent swelling. Determination of the
      angle of repose, Carr's index and Hausner ratio indicate the gum possess fairly
      good powder flow property. The antioxidant properties of the gum were evaluated
      by determining DPPH and hydroxyl scavenging activities, reducing power and total
      phenolic contents which showed the gum possess antioxidant property. 

PMID- 24875320
TI  - Chitosan nanocomposite films based on Ag-NP and Au-NP biosynthesis by Bacillus
      Subtilis as packaging materials.
AB  - Chitosan-silver (CS-Ag) and Chitosan-gold (CS-Au) nanocomposites films were
      synthesized by a simple chemical method. A local bacterial isolate identified as
      Bacillus subtilis ss subtilis was found to be capable to synthesize both silver
      nanoparticles (Ag-NP) and gold nanoparticles (Au-NP) from silver nitrate (AgNO3)
      and chloroauric acid (AuCl(4-)) solutions, respectively. The biosynthesis of both
      Ag-NP and Au-NP characterize using UV/vis spectroscopy, scanning electron
      microscopy (SEM), transmission electron microscopy (TEM) and X-ray diffraction
      (XRD), and then added to chitosan by different ratios (0.5, 1 and 2%). The
      prepared chitosan nanocomposites films were characterize using UV, XRD, SEM and
      TEM. Moreover, the antibacterial activity of the prepared films was evaluated
      against gram positive (Staphylococcus aureus) and gram negative bacteria
      (Pseudomonas aerugenosa), fungi (Aspergillus niger) and yeast (Candida albicans).
      Therefore, these materials can be potential used as antimicrobial agents in
      packaging applications. 

PMID- 24875318
TI  - Sulfated glucan can improve the immune efficacy of Newcastle disease vaccine in
      chicken.
AB  - To evaluate the immune effect of sulfated glucan from saccharomyces cerevisiae
      (SGSC) on chickens, two experiments were researched. In vitro experiment, the
      effects of SGSC on chicken splenic lymphocyte proliferation were determined. The
      results displayed that SGSC could significantly stimulate chicken splenic
      lymphocyte proliferation. In vivo experiment, 200 14-day-old chickens were
      averagely divided into 5 groups. The chickens, except blank control (BC) group,
      were vaccinated with Newcastle disease (ND) vaccine, repeated vaccination at 28
      days old. At the same time of the first vaccination, the chickens in three SGSC
      groups were injected, respectively, with the SGSC at low, medium and high
      concentrations, in vaccination control (VC) and BC group, with equal volume of
      physiological saline, once a day for three successive days. On days 7, 14, 21,
      28, 35 and 42 after the first vaccination, the lymphocyte proliferation, serum
      antibody titer and interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) were
      measured. The results showed that SGSC at suitable dose could significantly
      promote lymphocyte proliferation, enhance serum antibody titer, and improve serum
      IL-2 and IFN-gamma concentrations. It indicated that SGSC could significantly
      improve the immune efficacy of Newcastle disease vaccine, and would be as the
      candidate of a new-type immune adjuvant. 

PMID- 24875322
TI  - Fast removal of malachite green dye using novel superparamagnetic sodium alginate
      coated Fe3O4 nanoparticles.
AB  - In this study, superparamagnetic sodium alginate-coated Fe3O4 nanoparticles (Alg
      Fe3O4) as a novel magnetic adsorbent were prepared by in situ coprecipitation
      method, in which Fe3O4 nanoparticles were precipitated from FeCl3 and FeCl2 under
      alkaline medium in the presence of sodium alginate. The Alg-Fe3O4 nanoparticles
      were used for removal of malachite green (MG) from aqueous solutions using batch
      adsorption technique. The characterization of synthesized nanoparticles was
      performed using XRD, FTIR, TEM, TGA and vibrating sample magnetometer (VSM)
      techniques. FTIR analysis of synthesized nanoparticles provided the evidence that
      sodium alginate was successfully coated on the surface of Fe3O4 nanoparticles.
      The FT-IR and TGA characterization showed that the Alg-Fe3O4 nanoparticles
      contained about 14% (w/w) of sodium alginate. Moreover, TEM analysis indicated
      that the average diameter of the Alg-Fe3O4 nanoparticles was about 12nm. The
      effects of adsorbent dosage, pH and temperature were investigated on the
      adsorption properties of MG onto Alg-Fe3O4 nanoparticles. The equilibrium
      adsorption data were modeled using the Langmuir and Freundlich isotherms. The
      maximum adsorption capacity obtained from Langmuir isotherm equation was
      47.84mg/g. The kinetics of adsorption of MG onto Alg-Fe3O4 nanoparticles were
      investigated using the pseudo-first-order and pseudo-second-order kinetic models.
      The results showed that the adsorption of MG onto nanoparticles followed pseudo
      second-order kinetic model. 

PMID- 24875321
TI  - Antioxidant activity of carboxymethyl (1->3)-beta-d-glucan (from the sclerotium
      of Poria cocos) sulfate (in vitro).
AB  - (1->3)-beta-d-glucan derived from Poria cocos hardly exhibits bioactivities. To
      extend its use, three types of (1->3)-beta-d-glucan derivatives, which were
      sulfated (1->3)-beta-d-glucan (S-P), carboxymethyl (1->3)-beta-d-glucan (CMP) and
      carboxylmethyl (1->3)-beta-d-glucan sulfate (S-CMP), were synthesized. Potential
      antioxidant activities of S-P, CMP and S-CMP were evaluated in vitro. The
      experiments of scavenging abilities of free radicals were carried out, such as
      1,1-diphenyl-2-picrylhydrazyl (DPPH), superoxide anion and hydroxyl. Deeply study
      of the derivatives' inhibitory effect for lipid peroxidation, DNA oxidative
      damage, erythrocyte hemolysis, and malondialdehyde (MDA) production were
      determined. And S-CMP significantly (P<0.01) increased the antioxidant activity
      of beta-glucan. These results showed that multiple modifications of
      polysaccharides may bring the derivatives with excellent properties and various
      applications. 

PMID- 24875323
TI  - Optimization of selenylation conditions for a pectic polysaccharide and its
      structural characteristic.
AB  - CPP1b is a pectic polysaccharide isolated from Codonopsis pilosula, and it
      possesses potent antitumor activity. In this study, a HNO3-Na2SeO3 method was
      performed to synthesize selenium-CPP1b (sCPP1b). The effects of BaCl2 usage
      amount and HNO3 concentration on the yield and selenium content of sCPP1b were
      investigated by single-factor experiments. Reaction time, reaction temperature
      and the ratio of polysaccharide to Na2SeO3 were optimized by orthogonal
      experimental design at three levels of each of the three factors (L9(3)(4)) based
      on antitumor activity, selenium content and yield of sCPP1b. Our results showed
      that 5h of reaction time, 60 degrees C of reaction temperature, and 2:2 ratio of
      polysaccharide to Na2SeO3 were the optimal selenylation modification conditions.
      The validation experiments completed under the optimal conditions gave the mean
      selenium content and yield of sCPP1b were 478.17MUg/g (RSD=5.7%) and 595mg/g
      (RSD=1.6%), respectively. Selenylation modification can significantly increase
      the antitumor activity of CPP1b in vitro. The structural characterization of
      sCPP1b was further characterized by Fourier-transform infrared spectroscopy,
      thermogravimetric analysis, and high-performance gel permeation chromatography
      coupled with multi-angle laser light scattering. These structure analysis results
      indicated that sCPP1b has been successfully selenylation modified with similar
      structure to polysaccharide of CPP1b. 

PMID- 24875324
TI  - Protective effects of Gynostemma pentaphyllum polysaccharides on PC12 cells
      impaired by MPP(+).
AB  - The aim of the present study was to explore the neuroprotective effects of
      Gynostemma pentaphyllum polysaccharides (GP) in a 1-methyl-4-phenylpyridiniumion
      (MPP(+))-induced cellular model of Parkinson's disease (PD) and the underlying
      mechanisms. Our results indicated that exposure of PC12 cells to 1mM MPP(+)
      significantly decreased the cell viability when examined by MTT assay, LDH assay,
      and annexin-V-FITC and propidium iodide (PI) apoptosis detection assays. MPP(+)
      induced apoptosis in PC12 cells was accompanied by an increased Bax/Bcl-2 ratio,
      release of mitochondrial cytochrome c into the cytosol, activation of caspase-3/9
      and cleavage of poly (ADP-ribose) polymerase (PARP). However, pretreatment of
      PC12 cells with 50MUg/ml GP prior to MPP(+) exposure effectively attenuated the
      cytotoxicity and improved cell viability via inhibiting elevated Bax/Bcl-2 ratio,
      as well as the release of cytosolic cytochrome c. Furthermore, GP was effective
      in attenuating caspase-3/9 activation and cleavage of PARP in MPP(+)-exposed PC12
      cells. These results suggest that the GP has protective effects against MPP(+)
      induced neuronal apoptosis in PC12 cells by suppressing apoptosis-related
      protein, and therefore, might likely be a promising candidate for the treatment
      of Parkinson's disease (PD). 

PMID- 24875325
TI  - Water-soluble polysaccharides from agro-industrial by-products: functional and
      biological properties.
AB  - Water-soluble polysaccharides were isolated from almond (AWSP) and pistachio
      (PWSP) juice processing by-products. Their chemical and physical characteristics
      were determined using NMR and Infrared spectroscopic analysis. The complexities
      of the spectra reflected the heterogeneity of these polysaccharides. The ACE
      inhibitory activities (IC50 AWSP=2.81mgmL(-1) and IC50 PWSP=2.59mgmL(-1)) and
      antioxidant properties of AWSP and PWSP were investigated based on the DPPH
      radical-scavenging capacity assay (IC50 AWSP=2.87mgmL(-1) and IC50 PWSP=1.61mgmL(
      1)). Reducing power, beta-carotene bleaching inhibition (IC50AWSP=4.46mgmL(-1)
      and IC50 PWSP=3.39mgmL(-1)), and ferrous chelating assays (IC50 AWSP=0.22mgmL(-1)
      and IC50 PWSP=0.19mgmL(-1)) were also performed. The findings revealed that water
      soluble polysaccharides exhibited antioxidant and antihypertensive activities.
      AWSP and PWSP showed excellent interfacial concentration-dependent properties.
      Overall, the results suggested that both AWSP and PWSP are promising sources of
      natural antioxidants and ACE inhibitory agents and could, therefore, be used as
      alternative additives in food, pharmaceutical and cosmetic preparations. 

PMID- 24875327
TI  - Understanding ictogenesis in generalized epilepsies.
AB  - Generalized seizures are defined by bilateral symmetric and synchronous
      epileptiform EEG discharge over the entire convexity and commonly thought to
      involve the entire brain homogeneously. The characteristic 3-3.5 Hz Spike-and
      Wave pattern is conceived as a resonance phenomenon originating in a cortico
      thalamic circuit where it can start at variable sites. Investigations with EEG
      source analysis, magnetencephalography, positron emission tomography and single
      photon emission computerized tomography, functional magnetic resonance imaging
      and transcranial magnetic stimulation have suggested that generalized seizures
      have cortical onset and the thalamus has an essential role in the recruitment of
      a network comprising frontal, parietal and occipital cortex and the default mode
      network. Studies of reflex epileptic traits have shown that 'generalized'
      ictogenesis largely uses pre-existing functional anatomic networks normally
      serving physiological functions. It has therefore been proposed to consider these
      epilepsies as system disorders of the brain. Treatment is fundamentally
      pharmacological with a role for behavioral interventions. Generalized epileptic
      encephalopathies of early childhood are sometimes surgically remediable. 

PMID- 24875326
TI  - Survival and clinical metastases among prostate cancer patients treated with
      androgen deprivation therapy in Sweden.
AB  - OBJECTIVES: To examine the incidence of metastases and clinical course of
      prostate cancer patients who are without confirmed metastasis when initiating
      androgen deprivation therapy (ADT). METHODS: Retrospective cohort study conducted
      using electronic medical records from Swedish outpatient urology clinics linked
      to national mandatory registries to capture medical and demographic data.
      Prostate cancer patients initiating ADT between 2000 and 2010 were followed from
      initiation of ADT to metastasis, death, and/or end of follow-up. RESULTS: The 5
      year cumulative incidence (CI) of metastasis was 18%. Survival was 60% after 5
      years; results were similar for bone metastasis-free survival. The 5-year CI of
      castration-resistant prostate cancer (CRPC) was 50% and the median survival from
      CRPC development was 2.7 years. Serum prostate-specific antigen (PSA) levels and
      PSA doubling time were strong predictors of bone metastasis, any metastasis, and
      death. CONCLUSION: This study provides understanding of the clinical course of
      prostate cancer patients without confirmed metastasis treated with ADT in Sweden.
      Greater PSA values and shorter PSA doubling time (particularly <= 6 months) were
      associated with increased risk of bone metastasis, any metastasis, and death.

PMID- 24875330
TI  - Recent evolution of antibiotic resistance in the anaerobes as compared to
      previous decades.
AB  - Evolution of antibiotic resistance in the anaerobes was reviewed using recent
      data covering 2000-2013 as compared to previous years. All studies reported
      growing moxifloxacin resistance in Bacteroides/Parabacteroides spp. in Europe and
      USA and in Clostridium difficile in Europe. In half or more studies, the
      resistance rates in Bacteroides/Parabacteroides spp. to amoxicillin-clavulanate
      or ampicillin-sulbactam and clindamycin rose. In some studies, an increase in
      resistance was found in Bacteroides/Parabacteroides spp. to cefoxitin/cefotetan
      and carbapenems, in Prevotella spp. to penicillins, in anaerobic cocci to
      clindamycin and in Bacteroides/Parabacteroides spp. and C. difficile to
      metronidazole. Decreasing resistance was also observed, e.g. in
      Bacteroides/Parabacteroides spp. to cephalosporins, in Prevotella spp. and C.
      difficile to tetracyclines and in C. difficile to rifampin. No resistance changes
      were found to tigecycline, in Bacteroides/Parabacteroides spp. to chloramphenicol
      and in C. difficile to vancomycin. Factors influencing the resistance were the
      species, ribotype, country, hospital centre, antibiotic consumption and specimen
      type. In conclusion, the antibiotic resistance changes in the anaerobes are
      diverse and dynamic. Regular national surveys of resistance and both anaerobic
      microbiology and susceptibility testing of the isolates become more and more
      valuable. 

PMID- 24875331
TI  - Development and evaluation of new primers for PCR-based identification of
      Prevotella intermedia.
AB  - The aim of this study was to develop new Prevotella intermedia-specific PCR
      primers based on the 16S rRNA. The new primer set, Pi-192 and Pi-468, increased
      the accuracy of PCR-based P. intermedia identification and could be useful in the
      detection of P. intermedia as well as epidemiological studies on periodontal
      disease. 

PMID- 24875328
TI  - The amino-terminus of high voltage activated calcium channels: CaM you or can't
      you?

PMID- 24875333
TI  - Choosing your health insurance package: a method for measuring the public's
      preferences for changes in the national health insurance plan.
AB  - With rising healthcare expenditure and limited budgets available, countries are
      having to make choices about the content of health insurance plans. The views of
      the general population can help determine such priorities. In this article, we
      investigate whether preferences of the general population regarding the content
      of health insurance plans could be measured with the help of a stated preference
      method: the Basket Method (BM). In this method, people use an online tool to
      include or exclude healthcare interventions from their hypothetical insurance
      package; this then affects their monthly premium. The study was conducted in the
      Netherlands. In total, 1007 members of two panels managed by the NIVEL filled out
      an online questionnaire that included the BM. The suitability of the BM was
      tested with the help of five criteria, e.g. the BM's ability to distinguish
      between healthcare interventions. Our results suggest that the BM is suitable for
      measuring preferences of the general population regarding the content of the
      health insurance plan, as it performs well on most criteria. Policy makers can
      use these preferences when deciding the content of the health insurance plan. Its
      contents will then be more aligned to the population's needs and preferences. 

PMID- 24875334
TI  - Amputation characteristics vary by branch of service.
AB  - This study examines the amputees from the Army and Marine Corps, the two military
      branches that have sustained the majority of combat-related amputations. All U.S.
      service members who sustained major extremity amputations from October 2001
      through July 2011 were analyzed. Amputation levels, demographics, and mounted or
      dismounted status at injury were examined. There were 835 Army and 344 Marine
      amputees; 52.9% of all Marine amputees occurred during 2010 and 2011. Over 50% of
      Marine and 44% of Army amputees sustaining an amputation during 2010 and 2011
      sustained multiple amputations. Dismounted service members had significantly (p <
      .0001) higher Injury Severity Scores and were significantly more likely to
      sustain double (p = .0082) and triple (p < .0001) amputations than mounted
      personnel. Marine amputees were significantly (p < .0001) more likely to be
      dismounted than Army amputees. The number of multiple amputees increased
      substantially in 2010 and 2011. Marine amputees, particularly dismounted, are at
      an increased risk of sustaining multiple amputations. 

PMID- 24875335
TI  - Evidence-based medicine in military orthopaedics: are we doing our part?
AB  - The clinical application of evidence-based medicine is influenced by the quality
      of the published literature. Journals assign objective levels of evidence to
      articles to describe the quality and reliability of individual articles. Studies
      assigned levels I to III are considered higher quality studies. This study
      reviewed 60 continuous years of the American edition of the Journal of Bone and
      Joint Surgery to analyze trends in the quality of research published by U.S.
      military orthopaedic surgeons. Three hundred and six of 371 identified articles
      were assigned a level of evidence from I to V. These were then analyzed to
      determine if military orthopaedic surgeons were producing higher quality studies
      over time. Over time, the total number of articles published decreased. However,
      the number of higher quality studies and average level of evidence per decade
      improved over time. This trend toward publishing higher quality studies is
      consistent with the general orthopaedic community and highlights the need for
      continued work by the military orthopaedic community to conduct higher quality
      studies. 

PMID- 24875332
TI  - Axon guidance factor netrin-1 and its receptors regulate angiogenesis after
      cerebral ischemia.
AB  - Neurogenesis and angiogenesis play important roles in functional recovery after
      ischemic stroke. When cerebral ischemia occurs, axon regeneration can compensate
      for the loss of apoptotic neurons in the ischemic area. The formation of new
      blood vessels ameliorates the local decrease in blood supply, enhancing the
      supply of oxygen and nutrients to newly-formed neurons. New blood vessels also
      act as a scaffold for the migration of neuroblasts to the infarct area after
      ischemic stroke. In light of this, researchers have been actively searching for
      methods to treat cerebral infarction. Netrins were first identified as a family
      of proteins that mediate axon guidance and direct axon migration during
      embryogenesis. Later studies have revealed other functions of this protein
      family. In this review, we focus on netrin-1, which has been shown to be involved
      in axon migration and angiogenesis, which are required for recovery after
      cerebral ischemia. Thus, therapies targeting netrin-1 may be useful for the
      treatment of ischemic stroke. 

PMID- 24875336
TI  - Outcome of minimally invasive hip replacement in obese, overweight, and nonobese
      patients.
AB  - The goal of this study was to determine whether obesity affects implant
      positioning or early functional outcome after minimally invasive total hip
      replacement. The authors evaluated 119 patients who had undergone minimally
      invasive total hip replacement via a direct anterior approach. The patients were
      segregated according to World Health Organization body mass index categories:
      nonobese, overweight, or obese. Perioperative variables, resulting cup position,
      and early outcome (Harris Hip Score) were assessed. The only significant
      difference among the groups was mean operative time (obese > overweight >
      nonobese). Although the obese group's 2-year Harris Hip Score was the lowest, all
      patients had good to excellent results. In conclusion, minimally invasive hip
      replacement in obese patients provides early outcomes comparable to those in
      nonobese patients. 

PMID- 24875337
TI  - Pelvic crescent fractures: variations in injury mechanism and radiographic
      pattern.
AB  - Pelvic crescent fracture, also known as sacroiliac fracture-dislocation, is
      traditionally considered as a lateral compression injury and a vertically stable
      injury. Thirty consecutive cases were analyzed and it was found that 63% of cases
      were caused by lateral compression (LC), 27% by anteroposterior compression
      (APC), and 10% by vertical shear (VS). APC and VS injuries cause significant
      displacement of the anterior iliac fragment, but 21% of LC injury cases showed
      minimal displacement and were treated successfully with nonoperative treatment.
      Different injury mechanisms also produce different types of pelvic instability.
      More important, different injury mechanisms produce distinct radiographic
      fracture patterns regarding the obliquity of the fracture line and fracture
      surface. These differences in the fracture pattern will influence the decision of
      internal fixation options. Therefore, treatment of pelvic crescent fractures
      should be based on individual analysis of injury mechanism and radiographic
      fracture pattern. 

PMID- 24875339
TI  - Brachial plexus injury: a descriptive study of American football.
AB  - A stinger is a common, yet understudied, injury that involves stretching or
      compression of the brachial plexus, often occurring during contact sports. Five
      football teams, including high school, collegiate, and professional teams,
      completed questionnaires. Questions were designed to obtain descriptive
      information regarding the nature and consequence of this injury and assess
      effectiveness of current preventive measures. Three hundred and four surveys were
      returned with 153 players reporting a stinger in their career (50.3%). The
      prevalence increased with years played and was most common in running backs
      (69%), defensive linemen (60%), linebackers (55%), and defensive secondary (54%).
      Current protective equipment and neck-strengthening programs did not provide
      protective benefits. Players at greatest risk of developing a stinger include
      those having played 3 or more years and players whose primary position is running
      back, defensive back, or defensive lineman. Further study is needed to better
      evaluate the effectiveness of current preventive measures. 

PMID- 24875338
TI  - Effect of head and neck positioning on cerebral perfusion during shoulder
      arthroscopy in beach chair position.
AB  - The aim of this prospective cohort study was to investigate the effect of head
      and neck positioning on cerebral perfusion during shoulder arthroscopy in the
      beach chair position. Regional cerebral tissue oxygen saturation (rSO2) was
      monitored intraoperatively using near-infrared spectroscopy on 51 consecutive
      patients undergoing arthroscopic shoulder surgery in the beach chair position.
      The head of each subject was manipulated by the examiner and sequentially
      positioned for 45 seconds in terminal flexion, extension, bilateral rotation, and
      bilateral lateral bending. Decreases in rSO2 of 20% or greater from baseline were
      defined as a cerebral desaturation event (CDE). The association between head and
      neck position and cerebral perfusion was assessed. Eight percent of patients
      (4/51) experienced CDE during head and neck positioning. Body mass index was
      found to be a risk factor for CDE (p = .05). When comparing preoperative baseline
      rSO2 to intraoperative supine and intraoperative upright rSO2, there was no
      significant decrease in saturation levels for any of the six tested positions.
      Frequent intraoperative evaluations of the head and neck position as well as
      careful preoperative positioning may reduce the risk of position-related
      complications in patients undergoing elective shoulder arthroscopy in the beach
      chair position. In this study's patient population, however, head and neck
      position was not found to cause significant cerebral desaturation for the time
      period tested compared to preoperative baselines. 

PMID- 24875340
TI  - Use of emergency department services for hand, wrist, and forearm fractures in
      the United States in 2008.
AB  - The objective of this study was to determine demographic characteristics and
      epidemiology of hand, wrist, and forearm fracture patients treated in the
      emergency departments (EDs) to identify the at-risk populations. The Nationwide
      Emergency Department Sample database collected by the Agency for Healthcare
      Research and Quality was used to estimate ED visits for hand, wrist, and forearm
      fractures during 2008. The overall rate of ED visits for these injuries was 54
      per 10,000 population. Children aged 6 to 15 had the highest rate of ED visits at
      124 per 10,000. A secondary increase in ED visits occurred at age 50 and rose
      with age. Metacarpals were the most common fracture location in adults aged 16 to
      25, while radius and ulna were the most common fracture location in all other age
      groups. Demographic analysis identified children, adult males aged 16 to 25, and
      the elderly as target populations for preventive interventions. 

PMID- 24875341
TI  - "Zone of vulnerability" for radial nerve injury: anatomic study.
AB  - The authors of this study sought improved understanding of the radial nerve
      course through the brachium and hypothesized that the most proximal aspect of the
      triceps tendon (PATT) serves as a useful superficial landmark for localizing the
      nerve. It was also hypothesized that a poorly appreciated area of vulnerability
      for nerve injury exists where the radial nerve runs along the lateral cortex of
      the humerus proximal to its transit through the lateral intermuscular septum
      (LIMS). The authors assessed 33 fresh-frozen cadaveric specimens. A 6.7-cm span
      of the nerve lies directly on the periosteum of the humerus before piercing the
      LIMS. The proximal 4.6~cm abuts the posterior cortex. The final 2.1~cm just
      proximal to the LIMS runs along the lateral cortex. The nerve at the posterior
      midline of the humerus is 2.3~cm proximal to the level of the PATT. The radial
      nerve lies directly on the lateral humeral cortex for 2~cm proximal to its
      transit through the LIMS. The PATT appears to be a consistent and practical
      superficial landmark to determine the location of the radial nerve from a
      posterior approach. 

PMID- 24875342
TI  - Papillary endothelial hyperplasia in association with vascular malformation of
      the hand.
AB  - Vascular malformations are uncommonly encountered in the hand. This case report
      involves the unique case of a rapidly enlarging mass associated with a known
      vascular malformation. Final pathology revealed dense reactive fibrous tissue,
      with prominent blood vessels, consistent with a venous malformation and
      associated papillary endothelial hyperplasia. The intraoperative finding of two
      separately identifiable masses, one fibrotic and one vascular, has not previously
      been reported. 

PMID- 24875343
TI  - Anterior intrapelvic migration of femoral trial head requiring secondary surgical
      approach for retrieval.
AB  - The current report describes a revision total hip arthroplasty in which the trial
      femoral head disassociated during reduction and migrated into a soft tissue
      capsule of the true pelvis between the external iliac vein and corona mortise.
      The authors believe this previously undescribed migration pattern was created by
      the patient's history of recurrent dislocations. To retrieve the trial prosthesis
      without injuring the adjacent vasculature, a secondary surgical approach was
      utilized. The described case identifies the risk of pelvic migration in patients
      with a history of dislocations and reminds us that a secondary surgical approach
      should be considered to avoid devastating injury to the neighboring vasculature. 

PMID- 24875344
TI  - Adhesive capsulitis.
AB  - Adhesive capsulitis of the shoulder, commonly known as "frozen shoulder" or
      "frozen shoulder syndrome," is a self-limited painful condition that is quite
      common. In 1984, the prevalence of frozen shoulder was demonstrated at slightly
      greater than 2% in the general population. In the authors' practice, consisting
      primarily of orthopedic magnetic resonance imaging, this diagnosis is frequently
      seen in patients referred for evaluation of rotator cuff tear because the
      presenting symptoms are similar. 

PMID- 24875345
TI  - The d-p band-inversion topological insulator in bismuth-based skutterudites.
AB  - Skutterudites, a class of materials with cage-like crystal structure which have
      received considerable research interest in recent years, are the breeding ground
      of several unusual phenomena such as heavy fermion superconductivity, exciton
      mediated superconducting state and Weyl fermions. Here, we predict a new
      topological insulator in bismuth-based skutterudites, in which the bands involved
      in the topological band-inversion process are d- and p-orbitals, which is
      distinctive with usual topological insulators, for instance in Bi2Se3 and BiTeI
      the bands involved in the topological band-inversion process are only p-orbitals.
      Due to the present of large d-electronic states, the electronic interaction in
      this topological insulator is much stronger than that in other conventional
      topological insulators. The stability of the new material is verified by binding
      energy calculation, phonon modes analysis, and the finite temperature molecular
      dynamics simulations. This new material can provide nearly zero-resistivity
      signal current for devices and is expected to be applied in spintronics devices. 

PMID- 24875346
TI  - Prospective associations of vitamin D status with beta-cell function, insulin
      sensitivity, and glycemia: the impact of parathyroid hormone status.
AB  - Previous studies have yielded conflicting findings on the relationship between
      low vitamin D (25-OH-D) and impaired glucose homeostasis. In this context, we
      hypothesized that combined assessment of 25-OH-D with its regulator parathyroid
      hormone (PTH) may be required for optimal evaluation of the impact of vitamin D
      status on glucose metabolism. Thus, we evaluated the prospective associations of
      25-OH-D and PTH at 3 months postpartum with beta-cell function (Insulin Secretion
      Sensitivity Index-2 [ISSI-2]), insulin sensitivity (Matsuda index), and glycemia
      at 12 months postpartum in 494 women undergoing serial metabolic
      characterization. Notably, 32% of those with prediabetes/diabetes mellitus at 12
      months postpartum had both vitamin D deficiency and PTH in the highest tertile at
      3 months postpartum. On multiple-adjusted linear regression analyses, vitamin D
      deficiency/insufficiency with PTH in the highest tertile at 3 months
      independently predicted poorer beta-cell function (P = 0.03) and insulin
      sensitivity (P = 0.01) and increased fasting (P = 0.03) and 2-h glucose (P =
      0.002) at 12 months postpartum. In contrast, vitamin D deficiency/insufficiency
      with lower PTH did not predict these outcomes. In conclusion, only vitamin D
      deficiency/insufficiency with increased PTH is an independent predictor of beta
      cell dysfunction, insulin resistance, and glycemia, highlighting the need for
      consideration of the PTH/25-OH-D axis when studying the impact of vitamin D
      status on glucose homeostasis. 

PMID- 24875347
TI  - Soil adsorption studies of a rice herbicide, cyhalofop-butyl, in two texturally
      different soils of India.
AB  - The ability of herbicides to be adsorbed by the soil and sediment and their
      tendency to be desorbed are some of the most important factors affecting soil and
      water contamination. Therefore, a sorption study was conducted to evaluate the
      adsorption of cyhalofop-butyl, butyl (2R)-2-[4-(4-cyano-2-fluorophenoxy) phenoxy]
      propanoate, in the sandy clay loam and clayey soils using a batch equilibrium
      method. The adsorption of cyhalofop-butyl was found positively related with the
      clay and organic carbon content. Freundlich constants (Kf) of cyhalofop-butyl in
      the clayey and sandy clay loam were found to be 13.39 and 2.21, respectively.
      Sorption coefficients (Koc) and distribution coefficients (Kd) were found to be
      265.38 and 2,092.79, and 1.38 and 11.48, for sandy clay loam and clayey soils,
      respectively. The adsorption isotherm suggested a relatively higher affinity of
      cyhalofop-butyl to the adsorption sites at low equilibrium concentrations. The
      low value of the soil organic carbon partition coefficient (Koc) of cyhalofop
      butyl in the sandy loam soil suggested its weaker adsorption in soil and thus
      increased its risk of mobility into water sources; hence, it should be used
      judiciously to prevent groundwater contamination.

PMID- 24875348
TI  - Wavelet analysis of some rivers in SE Europe and selected climate indices.
AB  - The influence of some climatic oscillations and sunspot number on river flows in
      Romania, Ukraine, and Moldova is verified by using standard wavelet analyses. The
      selected climate oscillations are Arctic Oscillation (AO), Antarctic Oscillation
      (AAO), East Atlantic Oscillation (EAO), East Atlantic/West Russia Oscillation
      (EAWRO), NINO3.4, North Atlantic Oscillation (NAO), Pacific/North America
      Oscillation (PNAO), Pacific Decadal Oscillation (PDO), Polar/Eurasia Oscillation
      (PEO), Scandinavian Oscillation (ScandO), Southern Oscillation (SO), and West
      Pacific Oscillation (WPO). Forty-five hydrological stations from an area of
      45,000 km(2) were used in order to discover the spatial evolution of the
      periodicities found in rivers. The wavelet analysis is novel for the rivers in
      the study area. There is an important difference between the periodicities found
      in mountain and plateau areas and those found in the plain area. There is a
      general downstream increase in the confidence level of the identified periods,
      even if the atmospheric precipitation has more relevant periodicities in the
      mountain area. The periodicities can be grouped into two compact groups: 1-16.5
      and 27.8-55.6 years. The correlation matrix of the global wavelet spectrum (GWS)
      values indicates that NAO, EAWRO, PDO, and the sunspot number are the main
      factors that generate the periodicities in rivers. It is the first time when the
      influence of PDO on local rivers is proven. All river periodicities smaller than
      16 years have a confidence level of 0.95 or above, as proven by the GWS analysis
      of the daily discharge data, and are caused by multiple external factors.

PMID- 24875349
TI  - Groundwater quality assessment in the urban-west region of Zanzibar Island.
AB  - This paper highlights the levels of anions (nitrate, nitrite, sulfate, bromide,
      chloride, and fluoride) and cations (potassium, sodium, magnesium, and calcium)
      in selected springs and groundwater sources in the urban-west region of Zanzibar
      Island. The levels of total dissolved solids (TDS) and sodium adsorption ratio
      (SAR) were also studied. Thirty water samples were collected in December 2012
      from various types of water sources, which included closed hand-dug wells (CHDW),
      open hand-dug wells (OHDW), springwater (SW), public bore wells (PBW), and bore
      wells owned by private individuals (BWP), and analyzed after filtration and
      sometimes dilution. The cations were analyzed using inductively coupled plasma
      optical emission spectrometry (ICP-OES). The anions were analyzed by chemically
      suppressed ion chromatography (IC). The ranges of the levels of the investigated
      parameters were as follows: Na 13.68-3,656 mg L(-1), K 2.66-583 mg L(-1), Mg 0.63
      131.10 mg L(-1), Ca 16.79-189.9 mg L(-1), Cl(-) 8.61-4,340.97 mg L(-1), F(-) 0
      1.02 mg L(-1), Br(-) 0-10.88 mg L(-1), NO3(-) 0.18-342.4 mg L(-1), NO2(-) 0-1.39,
      SO4(2-) 4.43-534.02 mg L(-1), TDS 7-6,380 mg L(-1), and SAR 0.63-50. Except
      fluoride, most of the studied parameters in the water samples had concentrations
      beyond the permissible limits of the World Health Organization (WHO). The
      elevated concentrations are a result of seepage of contaminated water from on
      site septic tanks, pit latrines, landfill leachates, fertilizer applications, and
      domestic effluents. These results should alert domestic water stakeholders in
      Zanzibar to the urgent task of initiating a quick mitigation response to control
      these alarming water risks.

PMID- 24875350
TI  - Occurrence of aflatoxin M1 in UHT milk and infant formula samples consumed in
      Burdur, Turkey.
AB  - Aflatoxins are toxic fungal metabolites found in foods and feeds. Aflatoxin M1
      (AFM1), a metabolite of the potent carcinogen aflatoxin B1(AFB1), occurs in milk
      from animals consuming feed contaminated with AFB1. The aim of this study was to
      investigate the occurrence and levels of AFM1 in ultra-high temperature (UHT)
      milk and infant formula samples consumed in Burdur City. During 2011, 41 samples
      of UHT milk and 33 samples of infant formula were randomly collected from
      different supermarkets and drug stores. The occurrence and contamination levels
      of AFM1 in the samples were investigated using the competitive enzyme-linked
      immunoabsorbent assay (ELISA) method. AFM1 was detected in 30 samples (73.2%) in
      concentrations ranging from 6.42 to 71.33 ng/L (mean level, 17.76 ng/L).
      Altogether, only three (7.3%) samples of UHT milk were contaminated at levels
      above the Turkish legal limit (50 ng/L). However, AFM1 was not detected in all
      infant formula samples. It is concluded that despite the widespread occurrence of
      AFM1 in UHT milk samples, the contamination levels were not serious for public
      health.

PMID- 24875351
TI  - Delayed-onset interface fluid syndrome after laser-assisted in situ
      keratomileusis secondary to descemet stripping automated endothelial
      keratoplasty.

PMID- 24875354
TI  - A total synthesis of (+)-negamycin through isoxazolidine allylation.
AB  - The beta-amino acid antibiotic (+)-negamycin has been synthesised in ten steps
      from epichlorohydrin via Sakurai allylation of an isoxazolidine intermediate. The
      key allylation reaction proceeded with complete trans-selectivity, which is
      attributed to electrostatic attraction between the chlorine atom and the iminium
      ion in the Sakurai intermediate. 

PMID- 24875353
TI  - The association between physical environment and cycling to school among Turkish
      and Moroccan adolescents in Amsterdam.
AB  - OBJECTIVES: This study examined the effect of physical environment on cycling to
      and from school among boys and girls of Turkish and Moroccan origin living in
      Amsterdam. METHODS: The LASER study (n = 697) was an interview study that
      included information on cycling to and from school and the perceived physical
      environment. Objective information on physical environment was gathered from
      Statistics Netherlands and the Department for Research and Statistics at the
      Municipality of Amsterdam. Structural equation modelling with latent variables
      was applied, taking into account age, gender, self-assessed health, education,
      country of origin, and distance to school. RESULTS: For every unit increase in
      the latent variable scale for bicycle-friendly infrastructure, we observed a 21%
      increase in the odds for cycling to and from school. The association was only
      borderline statistically significant and disappeared after controlling for
      distance to school. The enjoyable environment was not associated with cycling to
      and from school after controlling for all background factors. CONCLUSIONS:
      Bicycle-friendly infrastructure and an enjoyable environment were not important
      factors for cycling to and from school among those with no cultural cycling
      background.

PMID- 24875352
TI  - Sources of European drug consumption data at a country level.
AB  - OBJECTIVES: This study aimed at outlining the characteristics of nationwide
      administrative databases monitoring drug consumption in Europe. METHODS: Internet
      and bibliographic databases (April 2010) were searched and experts in drug
      utilization (DU) research interviewed to find nationwide administrative medicines
      consumption databases in Europe, with data for the out- and inpatient healthcare
      sector. A questionnaire was developed to gather additional information. We
      collected data providers, websites, accessibility, data sources, healthcare
      settings, population coverage, medicines-related data, patient and prescriber
      data, periods covered, and linkage to other databases. RESULTS: Thirty-one
      administrative nationwide medicine consumption databases in 25 countries were
      identified. Questionnaires were responded for 20 databases. Eleven provided
      wholesalers' sales data, 11 on reimbursed, 5 on prescribed, and 4 on dispensing
      medicines. Fifteen databases provided inpatient drug consumption data, mainly
      wholesalers' sales. CONCLUSIONS: Nationwide administrative databases are of value
      to all stakeholders involved in the conduct and interpretation of post-marketing
      safety studies, and in the conduct of DU research. The endorsement of the
      anatomical therapeutic chemical/defined daily dose methodology by these databases
      contributes to data harmonization. However, there is still a lack of information
      on inpatient medicines consumption at a patient-level.

PMID- 24875357
TI  - Chronic haloperidol increases voltage-gated Na+ currents in mouse cortical
      neurons.
AB  - Typical antipsychotics are characterized by extrapyramidal syndrome (EPS).
      Previous studies demonstrated that typical antipsychotics could inhibit neuronal
      voltage-gated sodium channel (VGSC). However, EPS typically emerge only upon
      prolonged exposure. As a result, we examined effects of haloperidol, a prototype
      typical antipsychotic, on neuronal VGSC upon incubation for varying duration.
      Briefly, VGSC currents were activated and recorded using a whole-cell patch-clamp
      technique in primary culture of mouse cortical neurons. VGSC activity was
      inhibited by acute haloperidol exposure (for minutes), but enhanced in a time-
      and concentration-dependent manner by chronic haloperidol exposure (for hours).
      The effects of chronic haloperidol were associated with increased expression of
      VGSC subunits as well as corresponding electrophysiological channel properties.
      In summary, we found enhanced VGSC currents upon chronic haloperidol exposure in
      cortical neurons in contrast to inhibition by acute haloperidol exposure. Such a
      results may contribute to EPS of typical antipsychotics. 

PMID- 24875355
TI  - Negative transcriptional regulation of mitochondrial transcription factor A
      (TFAM) by nuclear TFAM.
AB  - The nuclear DNA-encoded mitochondrial transcription factor A (TFAM) is
      synthesized in cytoplasm and transported into mitochondria. TFAM enhances both
      transcription and replication of mitochondrial DNA. It is unclear, however,
      whether TFAM plays a role in regulating nuclear gene expression. Here, we
      demonstrated that TFAM was localized to the nucleus and mitochondria by
      immunostaining, subcellular fractionation, and TFAM-green fluorescent protein
      hybrid protein studies. In HT22 hippocampal neuronal cells, human TFAM (hTFAM)
      overexpression suppressed human Tfam promoter-mediated luciferase activity in a
      dose-dependent manner. The mitochondria targeting sequence-deficient hTFAM also
      repressed Tfam promoter activity to the same degree as hTFAM. It indicated that
      nuclear hTFAM suppressed Tfam expression without modulating mitochondrial
      activity. The repression required for nuclear respiratory factor-1 (NRF-1), but
      hTFAM did not bind to the NRF-1 binding site of its promoter. TFAM was co
      immunoprecipitated with NRF-1. Taken together, we suggest that nuclear TFAM down
      regulate its own gene expression as a NRF-1 repressor, showing that TFAM may play
      different roles depending on its subcellular localizations. 

PMID- 24875358
TI  - Structure determination of archaea-specific ribosomal protein L46a reveals a
      novel protein fold.
AB  - Three archaea-specific ribosomal proteins recently identified show no sequence
      homology with other known proteins. Here we determined the structure of L46a, the
      most conserved one among the three proteins, from Sulfolobus solfataricus P2
      using NMR spectroscopy. The structure presents a twisted beta-sheet formed by the
      N-terminal part and two helices at the C-terminus. The L46a structure has a
      positively charged surface which is conserved in the L46a protein family and is
      the potential rRNA-binding site. Searching homologous structures in Protein Data
      Bank revealed that the structure of L46a represents a novel protein fold. The
      backbone dynamics identified by NMR relaxation experiments reveal significant
      flexibility at the rRNA binding surface. The potential position of L46a on the
      ribosome was proposed by fitting the structure into a previous electron
      microscopy map of the ribosomal 50S subunit, which indicated that L46a contacts
      to domain I of 23S rRNA near a multifunctional ribosomal protein L7ae. 

PMID- 24875356
TI  - Studies on the mechanism of testicular dysfunction in the early stage of a
      streptozotocin induced diabetic rat model.
AB  - Streptozotocin (STZ) induced diabetic model has been widely used to study the
      effects of diabetes mellitus (DM) on male infertility, but it remains unclear
      whether the responses in this model are due to hyperglycemia or STZ per se. This
      study was designed to investigate the mechanism of STZ on testicular dysfunction.
      In the present study, sperm characteristics, serum testosterone, steroidogenic
      enzymes (StAR and 3beta-HSD), and the vimentin apical extension of sertoli cells
      decreased significantly in the STZ group compared with those in the normal
      controls (p<0.05), while Johnsen's score, testicular lipid peroxidation,
      spermatogenic cell apoptosis, and the expressions of NF-kappaB and Wnt4
      significantly increased (p<0.05). Insulin replacement mainly restored the
      decreased serum testosterone and steroidogenic enzymes, but not other parameters.
      The results indicated that spermatogenic dysfunction in the early stage of STZ
      induced diabetic rats was due to direct STZ cytotoxicity to sertoli cells, which
      could be regulated by Wnt4 and NF-kappaB, while steroidogenic dysfunction might
      be a direct or indirect consequence of insulin deficiency. The results suggested
      that STZ-induced diabetic model, at least in the early stage, is not suitable to
      study the diabetes-related spermatogenic dysfunction. 

PMID- 24875359
TI  - MiR-124 protects human hepatic L02 cells from H2O2-induced apoptosis by targeting
      Rab38 gene.
AB  - BACKGROUND: Hepatic ischemia reperfusion injury (IRI) is an inevitable clinical
      problem for liver surgeons. Because microRNAs (miRNAs) participate in various
      hepatic pathophysiological processes, this study aimed to explore the role and
      potential mechanism of miR-124 in hepatic IRI. METHODS: A liver IRI model was
      established in rats. The differential expression of miRNAs was detected using
      microarrays, and the expression of miR-124 was measured by qRT-PCR. A hydrogen
      peroxide (H2O2)-induced oxidative stress apoptosis model was also established.
      Cell apoptosis was detected by flow cytometry, and viability was detected by
      CCK8. The expression of Rab38 was detected by Western blotting and qRT-PCR, and a
      luciferase reporter assay was used to verify the expression of the miR-124 target
      gene. RESULTS: The miRNA spectrum changes dramatically after hepatic IRI in rats,
      and miR-124 is significantly down-regulated after liver IRI. MiR-124 decreases
      the H2O2-induced apoptosis of human hepatic L02 cells by up-regulating the
      activation of the AKT pathway. Rab38 is a target gene of miR-124 and is involved
      in H2O2-induced apoptosis. Interference with the expression of the Rab38 gene can
      protect hepatic L02 from H2O2-induced apoptosis by increasing the phosphorylation
      of AKT. These protective effects of miR-124 are attenuated by over-expression of
      Rab38. CONCLUSIONS: Many miRNAs are involved in hepatic IRI in rats, and miR-124
      is significantly decreased in this model. MiR-124 significantly decreases the
      H2O2-induced apoptosis of human hepatic L02 cells by targeting the Rab38 gene and
      activating the AKT pathway.

PMID- 24875360
TI  - Activation of farnesoid X receptor (FXR) protects against fructose-induced liver
      steatosis via inflammatory inhibition and ADRP reduction.
AB  - Fructose is a key dietary factor in the development of nonalcoholic fatty liver
      disease (NAFLD). Here we investigated whether WAY-362450 (WAY), a potent
      synthetic and orally active FXR agonist, protects against fructose-induced
      steatosis and the underlying mechanisms. C57BL/6J mice, fed 30% fructose for 8
      weeks, were treated with or without WAY, 30 mg/kg, for 20 days. The elevation of
      serum and hepatic triglyceride in mice fed 30% fructose was reversed by WAY
      treatment. Histologically, WAY significantly reduced triglyceride accumulation in
      liver, attenuated microphage infiltration and protected the junction integrity in
      intestine. Moreover, WAY remarkably decreased portal endotoxin level, and lowered
      serum TNFalpha concentration. In lipopolysaccharide (LPS)-induced NAFLD model,
      WAY attenuated serum TNFalpha level. Moreover, WAY suppressed LPS-induced
      expression of hepatic lipid droplet protein adipose differentiation-related
      protein (ADRP), down-regulation of it in mice fed 30% fructose. Furthermore, WAY
      repressed lipid accumulation and ADRP expression in a dose-dependent manner in
      palmitic acid (PA)-treated HepG2 and Huh7 cells. WAY suppressed TNFalpha-induced
      ADRP up-regulation via competing with AP-1 for ADRP promoter binding region.
      Together, our findings suggest that WAY, an FXR agonist, attenuates liver
      steatosis through multiple mechanisms critically involved in the development of
      hepatosteatosis, and represents a candidate for NAFLD treatment.

PMID- 24875367
TI  - Positive animal welfare states and encouraging environment-focused and animal-to
      animal interactive behaviours.
AB  - Affective neuroscience, incorporating neurophysiology and neuropsychology, is
      providing increasing evidence that certain behaviours of animals may be
      interpreted in terms of what they are intending to achieve, i.e. their goals. It
      is also providing evidence that allows inferences to be made about the affective
      contents of some goal-directed behaviours. These neuroscience-supported
      inferences are aligned with recommendations based on prior behaviour-based
      investigations of animals' preferences, aversions and priorities, and these
      observations together support the cautious use of particular behaviours to infer
      what the accompanying affects may be. In this review, therefore, some attention
      is given to negative affects and their relationships to poor animal welfare, but
      the primary focus is the positive affects animals may experience when they
      successfully engage in rewarding goal-directed behaviours, encapsulated in the
      concept of positive affective engagement. The review draws together reports of
      environment-focused and animal-to-animal interactive behaviours observed in a
      range of species and under diverse circumstances in order to illustrate the
      likely widespread occurrence of the positive affects that may accompany them.
      Particular consideration is given to affects that are potentially associated with
      some aspects of exploration and food acquisition in stimulus rich or impoverished
      environments, and to those that may be associated with aspects of the affiliative
      interactions of bonding or bond affirmation, maternal care, play and sexual
      activity. It is concluded that animals given the opportunity to engage in such
      activities may experience some positive affects. However, the intensity of an
      animal's experience of particular positive affects is likely to range from zero
      to very high because the associated behaviours occur intermittently, variation
      may occur during different phases of a goal-directed behaviour, and other
      positive or negative affects experienced at the same time may have greater
      impact. As good welfare is achieved both by minimising negative affects and
      promoting positive ones and as conscious sentient animals may be expected to have
      an interest in experiencing as little pain and as much pleasure as possible, it
      is argued that there is an ethical obligation to take practical steps to help
      them to achieve these outcomes. Such steps would include providing them with
      opportunities to express more behaviours that are associated with rewarding or
      satisfying experiences understood in terms of positive affective engagement.

PMID- 24875369
TI  - Hysteretic behaviour in a vacuum deposited submonolayer of single ion magnets.
AB  - With element-specific X-ray absorption spectroscopy and X-ray magnetic circular
      dichroism we have investigated submonolayer coverages of TbPc2 and DyPc2
      molecules sublimated on highly ordered pyrolytic graphite. We have studied the
      field dependence of the magnetization of the central lanthanide ion at very low
      temperatures. Even in zero applied magnetic field we still observe a remanence in
      the magnetization. Since there are neither intermolecular coupling nor magnetic
      interactions with the substrate, this remanent behaviour results just from single
      ion anisotropy. On the very inert surface of graphite at temperatures between 0.5
      K and 2 K the spin relaxation is slow enough to observe a memory effect in the
      timescale of the experimental measurements. 

PMID- 24875368
TI  - Twenty-Four-Month Results of Intravitreal Bevacizumab in Macular Edema Secondary
      to Branch Retinal Vein Occlusion.
AB  - PURPOSE: The aim of this study is to evaluate the long-term efficacy of
      intravitreal bevacizumab (IVB) in macular edema (ME) due to branch retinal vein
      occlusion (BRVO) in a real clinical practice setting at a tertiary referral
      center. METHODS: A retrospective analysis of a final total number of 35 eyes of
      35 patients with a 24-month follow-up was performed. RESULTS: At 24 months, mean
      best-corrected visual acuity improved by 0.09 LogMAR units from baseline (95% CI:
      -0.03-0.24, p = 0.0674). The mean CFT decreased by 75 microns (95% CI: 27-123, p
      = 0.0026). The median number of injections was 6 (IQR: 3-9). Macular edema showed
      complete resolution in 12 eyes (34.3%), responded partially in six eyes (17%),
      recurred in eight eyes (23%), and remained persistent in nine eyes (25.7%, three
      eyes at six months, one eye at 12 months, three eyes at 18 months and two eyes at
      24 months). CONCLUSION: Our study shows that treatment with IVB in patients with
      ME due to BRVO during a period of 24 months provided complete resolution of the
      ME in more than one-third of patients. In one-third of the cases, ME resolved
      partially or recurred and in less than one-third of patients ME remained
      persistent. Visual acuity increased significantly in 23% of patients and remained
      stable in the majority of patients. However, a median number of six injections
      was necessary to maintain a lasting beneficial effect. Further long-term
      prospective studies are required comparing intravitreal bevacizumab with other
      treatment modalities.

PMID- 24875370
TI  - Formulation for beginners.
AB  - OBJECTIVE: Developing a formulation is an important method of understanding the
      people we treat. Writing a formulation need not be seen as burdensome or
      difficult. Our objective is to provide a framework for the formulation process to
      make it more accessible for beginners. CONCLUSION: We describe a method that
      beginners can adopt easily and then build upon as their experience and knowledge
      broadens.

PMID- 24875372
TI  - Invited commentary: nighttime light exposure as a risk factor for obesity through
      disruption of circadian and circannual rhythms.
AB  - In this issue of the American Journal of Epidemiology, McFadden et al. (Am J
      Epidemiol. 2014;180(3):245-250) report findings on the relationship between light
      exposure at night and obesity from a cross-sectional study of United Kingdom
      women. Their research extends findings from a previous study with elderly
      participants by including a larger sample size of over 100,000 women and a
      broader age range of 16 years or older. The findings are consistent with animal
      studies showing that prolonged light exposure leads to weight gain. Humans'
      circadian, circannual, and metabolic regulatory systems evolved to be adaptive in
      environments that were quite different from those faced in modern industrial
      society. Technology has allowed exposures to levels and timing of light, nutrient
      intake, and physical activity never before possible. This commentary discusses
      how nighttime light exposure can increase the risk of obesity and the metabolic
      syndrome by disrupting circadian and circannual rhythms. 

PMID- 24875371
TI  - The relationship between obesity and exposure to light at night: cross-sectional
      analyses of over 100,000 women in the Breakthrough Generations Study.
AB  - There has been a worldwide epidemic of obesity in recent decades. In animal
      studies, there is convincing evidence that light exposure causes weight gain,
      even when calorie intake and physical activity are held constant. Disruption of
      sleep and circadian rhythms by exposure to light at night (LAN) might be one
      mechanism contributing to the rise in obesity, but it has not been well
      investigated in humans. Using multinomial logistic regression, we examined the
      association between exposure to LAN and obesity in questionnaire data from over
      100,000 women in the Breakthrough Generations Study, a cohort study of women aged
      16 years or older who were living in the United Kingdom and recruited during 2003
      2012. The odds of obesity, measured using body mass index, waist:hip ratio,
      waist:height ratio, and waist circumference, increased with increasing levels of
      LAN exposure (P < 0.001), even after adjustment for potential confounders such as
      sleep duration, alcohol intake, physical activity, and current smoking. We found
      a significant association between LAN exposure and obesity which was not
      explained by potential confounders we could measure. While the possibility of
      residual confounding cannot be excluded, the pattern is intriguing, accords with
      the results of animal experiments, and warrants further investigation. 

PMID- 24875373
TI  - Differential geographical risk of initial Pseudomonas aeruginosa acquisition in
      young US children with cystic fibrosis.
AB  - Pseudomonas aeruginosa is the sentinel respiratory pathogen in cystic fibrosis
      patients. We conducted a retrospective study to examine whether state of
      residence affected risk of P. aeruginosa acquisition among US children under 6
      years of age with cystic fibrosis by using data from the Cystic Fibrosis
      Foundation National Patient Registry, 2003-2009. The outcome was time to first
      isolation of P. aeruginosa from a respiratory culture. We used a Bayesian
      hierarchical Weibull regression model with interval-censored outcomes. Spatial
      random effects, included at the state level and modeled using an intrinsic
      conditional autoregressive prior, allowed estimation of the residual spatial
      correlation. The regression portion of the model was adjusted for demographic and
      disease characteristics potentially affecting P. aeruginosa acquisition. A total
      of 3,608 children met the inclusion criteria and were followed for an average of
      2.1 (standard deviation, 1.6) years. P. aeruginosa was cultured in 1,714 (48%)
      subjects. There was a moderately elevated spatial residual relative risk. An
      estimated 95% credible interval for the residual hazard ratio under 1 of the
      fitted models was 0.64-1.57; the strongest positive association was observed in
      the Southern states. The fact that risk for P. aeruginosa acquisition displayed
      spatial dependence suggests that regional factors, such as climate, may play an
      important role in P. aeruginosa acquisition.

PMID- 24875375
TI  - Immobilization of 5-aminopyridine-2-tetrazole on cross-linked polystyrene for the
      preparation of a new adsorbent to remove heavy metal ions from aqueous solution.
AB  - Novel 5-aminopyridine-2-tetrazole-functionalized polystyrene resin (APTZ-PS) was
      prepared by anchoring 5-aminopyridine-2-carbonitrile onto chloromethylated
      polystyrene beads (CMPS) and subsequently using the cyano-tetrazole conversion
      reaction. The APTZ-PS resin was characterized by Fourier transform infrared
      spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS) and specific surface
      area and pore size analyses. The adsorption experiments of the prepared resin for
      heavy metal ions were conducted by batch methods. The effects of the experimental
      conditions, such as pH, contact time and initial metal ion concentration on the
      adsorption properties of Cu(II), Pb(II) and Hg(II) were investigated. The results
      showed that the resin possessed perfect adsorption capacities for Cu(II), Pb(II)
      and Hg(II), and the selectivity was different from the commonly used
      iminodiacetic acid-chelating resin. The sorption kinetics of the three metal ions
      followed the pseudo-second-order equation. The adsorption isotherms for Cu(II)
      and Pb(II) could be better fitted by the Langmuir model than the Freundlich
      model, whereas the Freundlich model was the best for the Hg(II) ion. Even after
      five consecutive adsorption-desorption cycles, no obvious change in the
      adsorption capacity of the resin was found, which implied that the APTZ-PS resin
      was suitable for the efficient removal of heavy metal ions from aqueous solution.

PMID- 24875377
TI  - Positive Portrayals of Old Age Do Not Always Have Positive Consequences.
AB  - OBJECTIVES: The literature on "image of aging" suggests that exposure to positive
      portrayals of old age has positive downstream consequences for older adults. This
      study examined whether these positive consequences might have limits, such that
      they occurred for portrayals of old age that were positive, but not those that
      were extremely positive. METHOD: Younger and older adults were allowed to
      selectively view (Study 1) or were experimentally exposed to (Studies 2 and 3)
      portrayals of old age of different levels of positivity. Their attention (Study
      1) and physiological responses (Study 2) toward the portrayals, as well as
      perception of personal aging (Study 1) and memory performance (Study 3) after the
      exposure, were assessed. RESULTS: Findings from 3 studies suggested that older
      adults have a less negative perception of personal aging (Study 1) and a stronger
      calming physiological response (Study 2) when being exposed to portrayals of old
      age that were positive, but not extremely positive. Moreover, extremely positive
      portrayals lowered downstream memory performance (Study 3) and attracted less
      attention from older adults when they found these portrayals unrealistic (Study
      1). DISCUSSION: These findings pinpoint the conditions under which positive
      portrayals of old age may benefit older adults.

PMID- 24875378
TI  - Challenges and Opportunities for a Human Rights Frame in South Korea: Context and
      Strategizing in the Anti-Domestic Violence Movement.
AB  - Korean feminists are keenly aware that transnational feminists emphasize a human
      rights framework to eradicate violence against women. But in the 1990s, they
      based their anti-domestic violence campaign on a frame of "preservation of the
      family" because it was more culturally resonant at the time than a human rights
      frame. The results include passage of two legislative Acts, failure to implement
      as intended, and a continued search for a more effective frame. Ironically, the
      human rights frame has re-emerged as a possible solution.

PMID- 24875376
TI  - Assessment of neighborhood context in a nationally representative study.
AB  - OBJECTIVES: This paper introduces new measures of neighborhood context that are
      included in the second wave of the National Social Life, Health, and Aging
      Project (NSHAP). We describe the use of field interviewer ratings of respondents'
      neighborhood conditions, as well as the adaptation of existing measures for the
      assessment of neighborhood social context among urban and nonurban older adults.
      METHOD: We construct scales of neighborhood problems, neighborhood social
      cohesion, neighborhood social ties, and perceived neighborhood danger, and assess
      their reliability and validity. We then calculate descriptive statistics for
      measures of neighborhood context across respondent age, gender, and racial/ethnic
      background, and across low-, moderate-, and high-density residential blocks.
      RESULTS: We find that older women report greater neighborhood cohesion and more
      neighborhood ties than older men, but women also perceive more neighborhood
      danger. Black and Hispanic older adults reside in neighborhoods with more
      problems, lower cohesion, fewer social ties, and greater perceived danger.
      Neighborhood characteristics also vary across residential densities. Neighborhood
      problems and perceived danger increase with block-level density, but neighborhood
      social cohesion and social ties were lowest among residents of moderate-density
      blocks. DISCUSSION: The inclusion of neighborhood context measures in the second
      wave of NSHAP provides a unique opportunity to explore associations among
      neighborhood context, social connectedness, and indicators of health and function
      among older adults. We discuss limitations of the measures and provide
      recommendations for their use.

PMID- 24875374
TI  - Variation in the association between colorectal cancer susceptibility loci and
      colorectal polyps by polyp type.
AB  - We conducted a case-control study of the association between subsets of
      colorectal polyps, including adenomas and serrated polyps, and single-nucleotide
      polymorphisms (SNPs) related to colorectal cancer through prior genome-wide
      association studies (GWAS). Participants were enrollees in the Group Health
      Cooperative (Seattle, Washington) aged 24-79 years who received a colonoscopy
      from 1998 to 2007, donated a buccal or blood sample, and completed a structured
      questionnaire. We performed genotyping of 13 colorectal cancer susceptibility
      SNPs. Polytomous logistic regression models were used to estimate odds ratios and
      95% confidence intervals for associations between polyps and the colorectal
      cancer risk allele for each SNP under a log-additive model. Analyses included 781
      controls, 489 cases with adenoma, 401 cases with serrated polyps, and 188 cases
      with both polyp types. The following SNPs were associated with advanced adenomas:
      rs10936599, rs10795668, rs16892766, and rs9929218 (P < 0.05). For nonadvanced
      adenomas and for serrated polyps overall, only rs961253 was statistically
      significant (P < 0.05). These associations were in the same directions as those
      in prior colorectal cancer GWAS. No SNP was significantly associated with
      hyperplastic polyps, and only rs6983267 was significantly associated with sessile
      serrated polyps, but this association was opposite of that found in colorectal
      cancer GWAS. Our results suggest that the association between colorectal cancer
      susceptibility SNPs and colorectal polyps varies by polyp type. 

PMID- 24875379
TI  - The Impact of Sexual Assault Nurse Examiner Programs on Criminal Justice Case
      Outcomes: A Multisite Replication Study.
AB  - To address the underreporting and underprosecution of adult sexual assaults,
      communities throughout the United States have implemented multidisciplinary
      interventions to improve postassault care for victims and the criminal justice
      system response. One such model is the Sexual Assault Nurse Examiner (SANE)
      Program, whereby specially trained nurses provide comprehensive psychological,
      medical, and forensic services for sexual assault. In this study, we conducted a
      multisite evaluation of six SANE programs (two rural programs, two serving
      midsized communities, two urban) to assess how implementation of SANE programs
      affects adult sexual assault prosecution rates. At each site, most sexual
      assaults reported to law enforcement were never referred by police to prosecutors
      or were not charged by the prosecutor's office (80%-89%). Individually, none of
      the sites had a statistically significant increase in prosecution rates pre-SANE
      to post-SANE. However, when the data were aggregated across sites, thereby
      increasing statistical power, there was a significant effect such that cases were
      more likely to be prosecuted post-SANE as compared with pre-SANE. These findings
      suggest that the SANE intervention model does have a positive impact on sexual
      assault case progression in the criminal justice system. Nevertheless, there is
      still a pressing need for improvement as the vast majority of both pre-SANE and
      post-SANE resulted in nonreferral/no charges filed.

PMID- 24875380
TI  - Non-Small Cell Lung Carcinoma: An Overview on Targeted Therapy.
AB  - Non-small cell lung cancer (NSCLC) represents close to 90% of all lung cancers.
      When diagnosed, most cases are on an advanced and inoperable stage, with limited
      therapeutic options. Existing therapies have shown to be insufficient and novel
      strategies are urgently necessary. New advances in understanding the disease at
      cellular and molecular level however have helped researchers in devising novel
      strategies for therapy. These directed therapies limit cancer growth by targeting
      specific molecules related with tumor progression. Such strategies have shown to
      be more effective than chemotherapy and radiotherapy and can be complemented to
      existing therapeutic paradigm in augmenting beneficial outcome. Lung cancer could
      benefit from such innovative therapy. RNA interference (RNAi) is a sequence
      specific gene silencing mechanism and, since its discovery widespread
      applications have pointed it as a powerful tool in cancer treatment. Several on
      going clinical trials have been successfully demonstrating its potential as a
      novel therapeutic, including in the treatment of NSCLC. Here, we revise the
      recent findings concerning the therapeutic effects of molecular variations
      associated with NSCLC and where targeted therapies stand in its treatment, with
      special focus on RNAi-mediated gene silencing as a powerful strategy for NSCLC
      treatment. 

PMID- 24875381
TI  - Effect of vertebroplasty with bone filler device and comparison with balloon
      kyphoplasty.
AB  - PURPOSE: To evaluate the effect of vertebroplasty with a bone filler device
      compared with balloon kyphoplasty. METHODS: A total of 222 patients underwent
      operations from January 2008 to October 2012. One-level fractures numbered 169
      (86.7%) cases and two-level fractures numbered 26 (13.3%). A total of 221
      vertebral levels were analyzed consequently. Vertebral height, compression ratio,
      and segmental Cobb's angle were measured in preoperative and postoperative
      lateral X-rays. RESULTS: The compression ratio was the most influential parameter
      among three variables. Adjusted postoperative compression ratio was not
      significantly different between two operation groups. Bone cement leakage rates
      did not differ (p < 0.05). Bone cement distribution was spongy type in the
      majority of the vertebroplasty with bone filler device (94.5%), but only in 42.0%
      of the kyphoplasty. High bone densitometry readings and long period from
      diagnosis to operation were significant risk factors for bone cement leakage.
      CONCLUSIONS: Vertebroplasty with a bone filler device could achieve equivalent
      compression reduction and bone cement leakage rate, as well as greater sponge
      type bone cement distribution, which were advantages over balloon kyphoplasty.

PMID- 24875382
TI  - Axial suspension test to assess pre-operative spinal flexibility in patients with
      adolescent idiopathic scoliosis.
AB  - INTRODUCTION: An accurate description of the biomechanical behavior of the spine
      is crucial for the planning of scoliotic surgical correction as well as for the
      understanding of degenerative spine disorders. The current clinical assessments
      of spinal mechanics such as side-bending or fulcrum-bending tests rely on the
      displacement of the spine observed during motion of the patient. Since these
      tests focused solely on the spinal kinematics without considering mechanical
      loads, no quantification of the mechanical flexibility of the spine can be
      provided. METHODS: A spinal suspension test (SST) has been developed to
      simultaneously monitor the force applied on the spine and the induced vertebral
      displacements. The system relies on cervical elevation of the patient and
      orthogonal radiographic images are used to measure the position of the vertebras.
      The system has been used to quantify the spinal flexibility on five AIS patients.
      RESULTS: Based on the SST, the overall spinal flexibility varied between 0.3 
      degrees /Nm for the patient with the stiffer curve and 2  degrees /Nm for the
      less rigid curve. A linear correlation was observed between the overall spinal
      flexibility and the change in Cobb angle. In addition, the segmental flexibility
      calculated for five segments around the apex was 0.13 +/- 0.07  degrees /Nm,
      which is similar to intra-operative stiffness measurements previously published.
      CONCLUSIONS: In summary, the SST seems suitable to provide pre-operative
      information on the complex functional behavior and stiffness of spinal segments
      under physiological loading conditions. Such tools will become increasingly
      important in the future due to the ever-increasing complexity of the surgical
      instrumentation and procedures.

PMID- 24875383
TI  - Definition of Plant-Pathogenic Pseudomonas Genomospecies of the Pseudomonas
      syringae Complex Through Multiple Comparative Approaches.
AB  - A total of 34 phytopathogenic strain genomes belonging to the Pseudomonas
      syringae species complex and related species, including many pathotype strains,
      were assessed using average nucleotide identity (ANI) analysis. Their taxonomic
      relationships were consistently confirmed by the tetranucleotide frequency
      correlation coefficient (TETRA) values, multilocus sequence typing analysis
      (MLSA) performed with seven housekeeping genes, using both maximum likelihood and
      Bayesian methods, and split consensus network analyses. The ANI, MLSA, and split
      consensus analyses provided consistent and identical results. We confirmed the
      occurrence of the well-demarcated genomospecies inferred sensu Gardan et al.
      using DNA-DNA hybridization and ribotyping analyses. However, some P. syringae
      strains of the pathovars morsprunorum and lachrymans were placed in different
      genomospecies in our analyses. Genomospecies 1, 2, 4, 6, and 9 resulted well
      demarcated, whereas strains of genomospecies 3 and 8 had ANI values between 95
      and 96% in some cases, confirming that this threshold reveals very closely
      related species that might represent cases of splitting entities or the
      convergence of different species to the same ecological niche. This study
      confirms the robustness of the combination of genomic and phylogenetic approaches
      in revealing taxonomic relationships among closely related bacterial strains and
      provides the basis for a further reliable demarcation of the phytopathogenic
      Pseudomonas species. Within each species, the pathovars might represent distinct
      ecological units. The possibility of performing extensive and standardized host
      range and phenotypic tests with many strains of different pathovars can assist
      phytobacteriologists for better determining the boundaries of these ecological
      units.

PMID- 24875385
TI  - A Recombinant of Bean common mosaic virus Induces Temperature-Insensitive
      Necrosis in an I Gene-Bearing Line of Common Bean.
AB  - The I gene is a single, dominant gene conferring temperature-sensitive resistance
      to all known strains of Bean common mosaic virus (BCMV) in common bean (Phaseolus
      vulgaris). However, the closely related Bean common mosaic necrosis virus (BCMNV)
      induces whole plant necrosis in I-bearing genotypes of common bean, and the
      presence of additional, recessive genes is required to prevent this severe whole
      plant necrotic reaction caused by BCMNV. Almost all known BCMNV isolates have so
      far been classified as having pathotype VI based on their interactions with the
      five BCMV resistance genes, and all have a distinct serotype A. Here, we describe
      a new isolate of BCMV, RU1M, capable of inducing whole plant necrosis in the
      presence of the I gene, that appears to belong to pathotype VII and exhibits B
      serotype. Unlike other isolates of BCMV, RU1M was able to induce severe whole
      plant necrosis below 30 degrees C in bean cultivar Jubila that carries the I gene
      and a protective recessive gene bc-1. The whole genome of RU1M was cloned and
      sequenced and determined to be 9,953 nucleotides long excluding poly(A), coding
      for a single polyprotein of 3,186 amino acids. Most of the genome was found
      almost identical (>98%) to the BCMV isolate RU1-OR (also pathotype VII) that did
      not induce necrotic symptoms in 'Jubila'. Inspection of the nucleotide sequences
      for BCMV isolates RU1-OR, RU1M, and US10 (all pathotype VII) and three closely
      related sequences of BCMV isolates RU1P, RU1D, and RU1W (all pathotype VI)
      revealed that RU1M is a product of recombination between RU1-OR and a yet unknown
      potyvirus. A 0.8-kb fragment of an unknown origin in the RU1M genome may have led
      to its ability to induce necrosis regardless of temperature in beans carrying the
      I gene. This is the first report of a BCMV isolate inducing temperature
      insensitive necrosis in an I gene containing bean genotype.

PMID- 24875384
TI  - Postinfection Activity of Synthetic Antimicrobial Peptides Against Stemphylium
      vesicarium in Pear.
AB  - Brown spot of pear is a fungal disease of economic importance caused by
      Stemphylium vesicarium that affects the pear crops in Europe. Due to the
      characteristics of this disease and the moderate efficacy of available
      fungicides, the effectiveness of control measures is very limited; however,
      synthetic antimicrobial peptides (AMPs) may be a complement to these fungicides.
      In the present study, 12 AMPs of the CECMEL11 library were screened for
      fungicidal activity against S. vesicarium. In vitro experiments showed that eight
      AMPs significantly reduced the germination of conidia. The most effective
      peptides, BP15, BP22, and BP25, reduced fungal growth and sporulation at
      concentrations below 50 MUM. Leaf assays showed that preventive application of
      BP15 and BP22 did not reduce infection; however, when the peptides were applied
      curatively, infection was significantly reduced. The use of a BP15 fluorescein 5
      isothiocyanate conjugate revealed that the peptide binds to hyphae and germ tubes
      and produces malformations that irreversibly stop their development.

PMID- 24875386
TI  - Ecological interactions shape the dynamics of seed predation in Acrocomia
      aculeata (Arecaceae).
AB  - BACKGROUND: The complex network of direct and indirect relationships determines
      not only the species abundances but also the community characteristics such as
      diversity and stability. In this context, seed predation is a direct interaction
      that affects the reproductive success of the plant. For Acrocomia aculeata, the
      seed predation by Pachymerus cardo and Speciomerus revoili in post-dispersal may
      destroy more than 70% of the propagules and is influenced by the herbivory of the
      fruits during pre-dispersal. Fruits of plants with a higher level of herbivory
      during pre-dispersal are less attacked by predators in post-dispersal. We
      proposed a hypothesis that describes this interaction as an indirect defense
      mediated by fungi in a multitrophic interaction. As explanations, we proposed the
      predictions: i) injuries caused by herbivores in the fruits of A. aculeata favor
      fungal colonization and ii) the colonization of A. acuelata fruit by decomposing
      fungi reduces the selection of the egg-laying site by predator.
      METHODOLOGY/PRINCIPAL FINDINGS: For prediction (i), differences in the fungal
      colonization in fruits with an intact or damaged epicarp were evaluated in fruits
      exposed in the field. For prediction (ii), we performed fruit observations in the
      field to determine the number of eggs of P. cardo and/or S. revoili per fruit and
      the amount of fungal colonization in the fruits. In another experiment, in the
      laboratory, we use P. cardo females in a triple-choice protocol. Each insect to
      choose one of the three options: healthy fruits, fruits with fungus, or an empty
      pot. The proposed hypothesis was corroborated. Fruits with injuries in the
      epicarp had a higher fungal colonization, and fruits colonized by fungi were less
      attractive for egg-laying by seed predators. CONCLUSION/SIGNIFICANCE: This study
      emphasizes the importance of exploring the networks of interactions between
      multitrophic systems to understand the dynamics and maintenance of natural
      populations.

PMID- 24875387
TI  - Assessment of validity and predictability of the FiO2-SpO2 transfer-function in
      preterm infants.
AB  - In this paper an investigation of the gain, delay, and time-constant parameters
      of the transfer function describing the relation between fraction of inspired
      oxygen (FiO2) and oxygen saturation in the blood (SpO2) in preterm infants is
      presented. The parameters were estimated following FiO2 adjustments and goodness
      of fit was used to assess the validity of the model when using an assumed first
      order transfer function. For responses identified to be first-order, the
      estimated parameters were then clustered to identify areas where they tended to
      be concentrated. Each group described an operating region of the transfer
      function; thus, predicting the right operating region could potentially assist a
      range-based robust inspired oxygen controller to provide more optimal control by
      adapting itself to different clusters. Accordingly, the samples were assigned
      labels based on their cluster associations and 14 features available at the time
      of each adjustment were used as inputs to an artificial neural network to
      classify the clustered samples. The validity study suggested that 37% of the
      adjustments were followed by first-order responses. Prediction studies on the
      first-order responses indicated that the clusters could be predicted with an
      average accuracy of 64% when the parameters were divided into two groups. 

PMID- 24875390
TI  - Treatment of patients with acute deep vein thrombosis and/or pulmonary embolism:
      efficacy and safety of non-VKA oral anticoagulants in selected populations.
AB  - Venous thromboembolism (VTE), comprising deep vein thrombosis (DVT) and pulmonary
      embolism (PE), presents a large clinical burden. Prompt, effective and sustained
      anticoagulation is vital because of the risk of recurrent events, including life
      threatening PE, and complications such as post-thrombotic syndrome and chronic
      thromboembolic pulmonary hypertension. Dual-drug standard therapy is effective;
      however, parenteral low molecular weight heparin, coupled with routine
      coagulation monitoring and dose adjustment of vitamin K antagonists (VKAs),
      presents challenges for patients and healthcare providers. Non-VKA oral
      anticoagulants provide a simplified option for VTE treatment. Phase III studies
      have investigated rivaroxaban and apixaban as single-drug approaches, and
      edoxaban and dabigatran in conjunction with initial heparin therapy. These agents
      demonstrated non-inferiority to standard therapy, and most showed significant
      reductions in major bleeding. However, clinical information is limited in patient
      subgroups, e.g. fragile patients or patients with renal impairment or cancer, who
      may be at higher risk of bleeding and/or VTE. A prespecified pooled analysis of
      the EINSTEIN DVT and EINSTEIN PE studies (8281 patients), undertaken to evaluate
      clinical outcomes with rivaroxaban versus standard therapy, confirmed the non
      inferiority of rivaroxaban, with significant reductions in major bleeding and
      fewer intracranial and retroperitoneal bleeding events. Consistent efficacy and
      safety were observed with rivaroxaban, irrespective of fragility, cancer or clot
      severity. The introduction of the non-VKA oral anticoagulants and approval of
      rivaroxaban in the EU, US and Canada for the treatment and secondary prevention
      of DVT and PE offer the potential for improvements in effective care across a
      broad spectrum of patients with VTE. 

PMID- 24875388
TI  - Human CD4+ T cell responses to the dog major allergen Can f 1 and its human
      homologue tear lipocalin resemble each other.
AB  - Lipocalin allergens form a notable group of proteins, as they contain most of the
      significant respiratory allergens from mammals. The basis for the allergenic
      capacity of allergens in the lipocalin family, that is, the development of T
      helper type 2 immunity against them, is still unresolved. As immunogenicity has
      been proposed to be a decisive feature of allergens, the purpose of this work was
      to examine human CD4+ T cell responses to the major dog allergen Can f 1 and to
      compare them with those to its human homologue, tear lipocalin (TL). For this,
      specific T cell lines were induced in vitro from the peripheral blood mononuclear
      cells of Can f 1-allergic and healthy dog dust-exposed subjects with peptides
      containing the immunodominant T cell epitopes of Can f 1 and the corresponding TL
      peptides. We found that the frequency of Can f 1 and TL-specific T cells in both
      subject groups was low and close to each other, the difference being about two
      fold. Importantly, we found that the proliferative responses of both Can f 1 and
      TL-specific T cell lines from allergic subjects were stronger than those from
      healthy subjects, but that the strength of the responses within the subject
      groups did not differ between these two antigens. Moreover, the phenotype of the
      Can f 1 and TL-specific T cell lines, determined by cytokine production and
      expression of cell surface markers, resembled each other. The HLA system appeared
      to have a minimal role in explaining the allergenicity of Can f 1, as the
      allergic and healthy subjects' HLA background did not differ, and HLA binding was
      very similar between Can f 1 and TL peptides. Along with existing data on
      lipocalin allergens, we conclude that strong antigenicity is not decisive for the
      allergenicity of Can f 1. 

PMID- 24875389
TI  - Prospective study of leptospirosis transmission in an urban slum community: role
      of poor environment in repeated exposures to the Leptospira agent.
AB  - BACKGROUND: Leptospirosis has emerged as an urban health problem as slum
      settlements have rapidly spread worldwide and created conditions for rat-borne
      transmission. Prospective studies have not been performed to determine the
      disease burden, identify risk factors for infection and provide information
      needed to guide interventions in these marginalized communities.
      METHODOLOGY/PRINCIPAL FINDINGS: We enrolled and followed a cohort of 2,003
      residents from a slum community in the city of Salvador, Brazil. Baseline and one
      year serosurveys were performed to identify primary and secondary Leptospira
      infections, defined as respectively, seroconversion and four-fold rise in
      microscopic agglutination titers. We used multinomial logistic regression models
      to evaluate risk exposures for acquiring primary and secondary infection. A total
      of 51 Leptospira infections were identified among 1,585 (79%) participants who
      completed the one-year follow-up protocol. The crude infection rate was 37.8 per
      1,000 person-years. The secondary infection rate was 2.3 times higher than that
      of primary infection rate (71.7 and 31.1 infections per 1,000 person-years,
      respectively). Male gender (OR 2.88; 95% CI 1.40-5.91) and lower per capita
      household income (OR 0.54; 95% CI, 0.30-0.98 for an increase of $1 per person per
      day) were independent risk factors for primary infection. In contrast, the 15-34
      year age group (OR 10.82, 95% CI 1.38-85.08), and proximity of residence to an
      open sewer (OR 0.95; 0.91-0.99 for an increase of 1 m distance) were significant
      risk factors for secondary infection. CONCLUSIONS/SIGNIFICANCE: This study found
      that slum residents had high risk (>3% per year) for acquiring a Leptospira
      infection. Re-infection is a frequent event and occurs in regions of slum
      settlements that are in proximity to open sewers. Effective prevention of
      leptospirosis will therefore require interventions that address the
      infrastructure deficiencies that contribute to repeated exposures among slum
      inhabitants.

PMID- 24875391
TI  - Cell reorientation under cyclic stretching.
AB  - Mechanical cues from the extracellular microenvironment play a central role in
      regulating the structure, function and fate of living cells. Nevertheless, the
      precise nature of the mechanisms and processes underlying this crucial cellular
      mechanosensitivity remains a fundamental open problem. Here we provide a novel
      framework for addressing cellular sensitivity and response to external forces by
      experimentally and theoretically studying one of its most striking manifestations
      -cell reorientation to a uniform angle in response to cyclic stretching of the
      underlying substrate. We first show that existing approaches are incompatible
      with our extensive measurements of cell reorientation. We then propose a
      fundamentally new theory that shows that dissipative relaxation of the cell's
      passively-stored, two-dimensional, elastic energy to its minimum actively drives
      the reorientation process. Our theory is in excellent quantitative agreement with
      the complete temporal reorientation dynamics of individual cells measured over a
      wide range of experimental conditions, thus elucidating a basic aspect of
      mechanosensitivity.

PMID- 24875392
TI  - Test-retest reliabilities of resting-state FMRI measurements in human brain
      functional connectomics: a systems neuroscience perspective.
AB  - Resting-state functional magnetic resonance imaging (RFMRI) enables researchers
      to monitor fluctuations in the spontaneous brain activities of thousands of
      regions in the human brain simultaneously, representing a popular tool for macro
      scale functional connectomics to characterize normal brain function, mind-brain
      associations, and the various disorders. However, the test-retest reliability of
      RFMRI remains largely unknown. We review previously published papers on the test
      retest reliability of voxel-wise metrics and conduct a meta-summary reliability
      analysis of seven common brain networks. This analysis revealed that the
      heteromodal associative (default, control, and attention) networks were mostly
      reliable across the seven networks. Regarding examined metrics, independent
      component analysis with dual regression, local functional homogeneity and
      functional homotopic connectivity were the three mostly reliable RFMRI metrics.
      These observations can guide the use of reliable metrics and further improvement
      of test-retest reliability for other metics in functional connectomics. We
      discuss the main issues with low reliability related to sub-optimal design and
      the choice of data processing options. Future research should use large-sample
      test-retest data to rectify both the within-subject and between-subject
      variability of RFMRI measurements and accelerate the application of functional
      connectomics. 

PMID- 24875395
TI  - A QM/MM study of the catalytic mechanism of aspartate ammonia lyase.
AB  - Aspartate ammonia lyase (Asp) is one of three types of ammonia lyases specific
      for aspartate or its derivatives as substrates, which catalyzes the reversible
      reaction of l-aspartate to yield fumarate and ammonia. In this paper, the
      catalytic mechanism of Asp has been studied by using combined quantum
      mechanical/molecular-mechanical (QM/MM) approach. The calculation results
      indicate that the overall reaction only contains two elementary steps. The first
      step is the abstraction of Cbeta proton of l-aspartate by Ser318, which is
      calculated to be rate limiting. The second step is the cleavage of CalphaN bond
      of l-aspartate to form fumarate and ammonia. Ser318 functions as the catalytic
      base, whereas His188 is a dispensable residue, but its protonation state can
      influence the active site structure and the existing form of leaving amino group,
      thereby influences the activity of the enzyme, which can well explain the pH
      dependence of enzymatic activity. Mutation of His188 to Ala only changes the
      active site structure and slightly elongates the distance of Cbeta proton of
      substrate with Ser318, causing the enzyme to remain significant but reduced
      activity. 

PMID- 24875393
TI  - A genome-wide assessment of the role of untagged copy number variants in type 1
      diabetes.
AB  - Genome-wide association studies (GWAS) for type 1 diabetes (T1D) have
      successfully identified more than 40 independent T1D associated tagging single
      nucleotide polymorphisms (SNPs). However, owing to technical limitations of copy
      number variants (CNVs) genotyping assays, the assessment of the role of CNVs has
      been limited to the subset of these in high linkage disequilibrium with tag SNPs.
      The contribution of untagged CNVs, often multi-allelic and difficult to genotype
      using existing assays, to the heritability of T1D remains an open question. To
      investigate this issue, we designed a custom comparative genetic hybridization
      array (aCGH) specifically designed to assay untagged CNV loci identified from a
      variety of sources. To overcome the technical limitations of the case control
      design for this class of CNVs, we genotyped the Type 1 Diabetes Genetics
      Consortium (T1DGC) family resource (representing 3,903 transmissions from parents
      to affected offspring) and used an association testing strategy that does not
      necessitate obtaining discrete genotypes. Our design targeted 4,309 CNVs, of
      which 3,410 passed stringent quality control filters. As a positive control, the
      scan confirmed the known T1D association at the INS locus by direct typing of the
      5' variable number of tandem repeat (VNTR) locus. Our results clarify the fact
      that the disease association is indistinguishable from the two main polymorphic
      allele classes of the INS VNTR, class I-and class III. We also identified novel
      technical artifacts resulting into spurious associations at the somatically
      rearranging loci, T cell receptor, TCRA/TCRD and TCRB, and Immunoglobulin heavy
      chain, IGH, loci on chromosomes 14q11.2, 7q34 and 14q32.33, respectively.
      However, our data did not identify novel T1D loci. Our results do not support a
      major role of untagged CNVs in T1D heritability.

PMID- 24875394
TI  - Surveillance for emerging biodiversity diseases of wildlife.

PMID- 24875397
TI  - Study of circulating hepcidin in association with iron excess, metabolic
      syndrome, and BMP-6 expression in granulosa cells in women with polycystic ovary
      syndrome.
AB  - OBJECTIVE: To identify the role of hepcidin in polycystic ovary syndrome (PCOS)
      patients. DESIGN: Cross-sectional case-control study. SETTING: Academic medical
      center. PATIENT(S): Sixty-seven PCOS patients and 94 healthy parous women
      volunteered for the study. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Serum
      levels of hepcidin, hormone and lipid profiles, parameters of iron and glucose
      metabolism, high-sensitivity C-reactive protein (hs-CRP), and bone morphogenetic
      protein 6 (BMP-6) mRNA expressions in the granulosa cells (GCs). RESULT(S): PCOS
      patients showed increased serum iron concentration and higher circulating
      hepcidin levels compared with control subjects, even with only lean subjects.
      Circulating hepcidin correlated with iron parameters, androgen index, hs-CRP, and
      fasting glucose and insulin levels, and with iron and ferritin levels after
      multiple regression analysis. We analyzed BMP-6 mRNA expression in the 89 GCs
      from nine PCOS patients and five non-PCOS women with the use of quantitative real
      time polymerase chain reaction, and no correlations existed between iron
      parameters, including circulating hepcidin, and BMP-6 expression in the GCs from
      PCOS women. CONCLUSION(S): PCOS patients had iron excess and higher hepcidin
      levels, which are associated with metabolic derangements. Circulating hepcidin is
      appropriately increased relative to the iron burden even in PCOS women,
      suggesting that iron excess in PCOS women does not result from a defect in the
      production of hepcidin. But there were no correlations between iron parameters
      and the expression of the BMP-6 in GCs from PCOS patients.

PMID- 24875396
TI  - Follicular-phase ovarian follicular fluid and plasma cytokine profiling of
      natural cycle in vitro fertilization patients.
AB  - OBJECTIVE: To characterize follicular fluid (FF) and systemic cytokine profiles
      at various time points during the natural-cycle follicular and periovulatory
      phases. DESIGN: Observational clinical study across two consecutive cycles.
      SETTING: Hospital-based in vitro fertilization program. PATIENT(S): Ten women
      undergoing modified natural-cycle in vitro fertilization (MNC-IVF).
      INTERVENTION(S): Plasma and follicular fluid (FF) collection. MAIN OUTCOME
      MEASURE(S): Forty FF cytokine concentrations from individual follicles and plasma
      from each patient were determined by fluid-phase multiplex immunoassay in two
      consecutive cycles: 1) tracking cycle-midfollicular or luteal surge; and 2)
      treatment cycle-periovulatory (at the time of MNC-IVF). Demographic, cycle, and
      cytokine data were compared with the use of chi-square, paired-scores t test, or
      Wilcoxon signed ranks tests. RESULT(S): Fluctuations in various FF cytokines were
      evident during the follicular phase: Levels of interleukin (IL) 6 and IL-8 were
      higher in periovulatory samples, and IL-1 receptor antagonist and vascular
      endothelial growth factor were elevated earlier in the cycle. Luteal surge
      profiles were similar to those found in periovulatory samples. Conversely,
      circulatory cytokine concentrations were more stable during the follicular phase.
      CONCLUSION(S): These findings present an extensive physiologic reference profile
      of FF cytokines associated with antral folliculogenesis and highlight the
      compartmentalization of systemic and intraovarian cytokine networks in natural
      cycles.

PMID- 24875398
TI  - Assessment of anovulation in eumenorrheic women: comparison of ovulation
      detection algorithms.
AB  - OBJECTIVE: To compare previously used algorithms to identify anovulatory
      menstrual cycles in women self-reporting regular menses. DESIGN: Prospective
      cohort study. SETTING: Western New York. PATIENT(S): Two hundred fifty-nine
      healthy, regularly menstruating women followed for one (n=9) or two (n=250)
      menstrual cycles (2005-2007). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S):
      Prevalence of sporadic anovulatory cycles identified using 11 previously defined
      algorithms that use E2, P, and LH concentrations. RESULT(S): Algorithms based on
      serum LH, E2, and P levels detected a prevalence of anovulation across the study
      period of 5.5%-12.8% (concordant classification for 91.7%-97.4% of cycles). The
      prevalence of anovulatory cycles varied from 3.4% to 18.6% using algorithms based
      on urinary LH alone or with the primary E2 metabolite, estrone-3-glucuronide,
      levels. CONCLUSION(S): The prevalence of anovulatory cycles among healthy women
      varied by algorithm. Mid-cycle LH surge urine-based algorithms used in over-the
      counter fertility monitors tended to classify a higher proportion of anovulatory
      cycles compared with luteal-phase P serum-based algorithms. Our study
      demonstrates that algorithms based on the LH surge, or in conjunction with
      estrone-3-glucuronide, potentially estimate a higher percentage of anovulatory
      episodes. Addition of measurements of postovulatory serum P or urine pregnanediol
      may aid in detecting ovulation.

PMID- 24875399
TI  - Mullerian duct anomalies diagnosed by saline contrast sonohysterography:
      prevalence in a general population.
AB  - OBJECTIVE: To estimate the prevalence of uterine mullerian duct anomalies in a
      general population. DESIGN: Cross-sectional study. SETTING: University hospital
      in collaboration with the Danish Civil Registry. PATIENT(S): A total of 1,654
      women randomly recruited from a general population; 686 women were eligible and
      accepted inclusion (429 pre- and 257 postmenopausal). Saline contrast
      sonohysterography (SCSH) was finally performed in 622 women (aged 20-74 years)
      (the procedure was impossible owing to cervical stenosis in 58, contraindicated
      in 2, other patient-related factors in 4). INTERVENTION(S): The shape of the
      uterus was dynamically evaluated in the transversal and longitudinal planes
      during SCSH and classified in accordance with American Fertility Society as
      normal, arcuate, septate (partial, complete), bicorn (partial, complete), or
      unicorn. History of previous miscarriage and menstrual cycle was obtained by a
      questionnaire. MAIN OUTCOME MEASURE(S): Prevalence of mullerian anomalies,
      miscarriage, and oligomenorrhea. RESULT(S): The overall prevalence of mullerian
      anomalies was 9.8% (61 of 622) (95% confidence interval [CI] 7.5-12.1). The
      majority had arcuate uteri (n=42, 6.8%), 17 partial septate (2.7%), 1 complete
      septate (1.6%), and 1 unicorn uterus (1.6%). Mullerian anomalies were
      significantly more frequently diagnosed in nulliparous (20% [26 of 128]) compared
      with parous women (7% [35 of 494]). Mullerian anomalies were more frequent in
      women with oligomenorrhea compared with women with normal menstrual periods (19%
      [15 of 79] vs. 10% [34 of 339]). One first-trimester miscarriage or multiple
      miscarriages (more than one) were not significantly more frequent in
      premenopausal women with mullerian anomalies compared with women with normal
      shaped uteri (24% [6 of 25] vs. 22% [57 of 265]). CONCLUSION(S): In a general
      population examined by SCSH the prevalence of Mullerian anomalies is estimated at
      9.8%. Mullerian anomalies were more frequent in nulliparous women. Both impaired
      fertility and a pregnancy-associated modulation of the uterine corpus are among
      explanations. Mullerian anomalies were associated with oligomenorrhea in
      premenopausal women. In this general population there was no association between
      miscarriage and mullerian anomalies; however, the number of cases was limited.

PMID- 24875400
TI  - Voluntary and involuntary childlessness in female veterans: associations with
      sexual assault.
AB  - OBJECTIVE: To assess associations between lifetime sexual assault and
      childlessness in female veterans. DESIGN: Cross-sectional, computer-assisted
      telephone interview study. SETTING: Two Midwestern Veterans Administration (VA)
      medical centers. PATIENT(S): A total of 1,004 women aged <=52 years, VA-enrolled
      between 2000 and 2008. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S):
      Sociodemographic variables, reproductive history and care utilization, and mental
      health. RESULT(S): A total of 620 veterans (62%) reported at least one attempted
      or completed sexual assault in their lifetime (LSA). Veterans with LSA more often
      self-reported a history of pregnancy termination (31% vs. 19%) and infertility
      (23% vs. 12%), as well as sexually transmitted infection (42% vs. 27%),
      posttraumatic stress disorder (32% vs. 10%), and postpartum dysphoria (62% vs.
      44%). Lifetime sexual assault was independently associated with termination and
      infertility in multivariate models; sexually transmitted infection, posttraumatic
      stress disorder, and postpartum dysphoria were not. The LSA by period of life was
      as follows: 41% of participants in childhood, 15% in adulthood before the
      military, 33% in military, and 13% after the military (not mutually exclusive).
      Among the 511 who experienced a completed LSA, 23% self-reported delaying or
      foregoing pregnancy because of their assault. CONCLUSION(S): This study
      demonstrated associations between sexual assault history and pregnancy
      termination, delay or avoidance (voluntary childlessness), and infertility
      (involuntary childlessness) among female veterans. Improved gender-specific
      veteran medical care must attend to these reproductive complexities.

PMID- 24875402
TI  - A novel dual-switch fluorescent probe for Cr(III) ion based on PET-FRET
      processes.
AB  - Two different strategies for photoinduced electron transfer (PET) and
      fluorescence resonance energy transfer (FRET) have been designed and combined
      into one sensing system. The novel probe NNRhB was developed based on 1,8
      naphthalimide and rhodamine moieties, in which two fluorophores are sensitive to
      the presence of Cr(3+) in different chromium ion concentration regimens.
      Therefore, the proposed sensing system represents dual-switch states and
      segmented detection behavior, with the fluorescence emission color spans from
      green to orange over an increasing Cr(3+) concentration gradient. When excited in
      the visible region, the initial emission band at 537 nm was enhanced. That was
      attributed to the suppression of the PET process, which arose from Cr(3+)
      coordination with a 1,8-naphthalimide derivative. At a sufficiently high
      concentration of Cr(3+) (over 9 MUM), the spirolactam rhodamine component in
      NNRhB converted to the opened form as a result of Cr(3+) coordination, which
      turned the emission color from green to orange via FRET. The fluorescence
      phenomena of the compound 1 and compound 2 split from compound NNRhB confirm our
      hypothesis of the spectral response mechanisms. Moreover, compared with a single
      fluorescent response in compound 1 or compound 2, the dual-switch fluorescent
      probe NNRhB shows a more sensitive and distinct visual detection ability for
      Cr(3+) ions. This probe affords a high selectivity and sensitivity to Cr(3+) from
      30 nM to 80 MUM; the detection limit was 0.14 nM. The results of practical
      application experiments suggest that the Cr(3+)-selective ligand prepared here
      may provide an effective strategy for detection of Cr(3+) in environmental and
      biological applications.

PMID- 24875403
TI  - Au nanorod quartets and Raman signal enhancement: towards the design of plasmonic
      platforms.
AB  - Quartets of Au nanorods were designed by combining the methodologies of lateral
      and longitudinal assemblies. A high electric field prevailing at the quartet
      junctions results in large enhancement in the Raman signals of molecules. FDTD
      simulations showed that the displacement of the lateral dimers in quartets
      expands the scope of hot spot distribution. 

PMID- 24875401
TI  - Dietary acrylamide and human cancer: a systematic review of literature.
AB  - Cancer remains the second leading cause of death in the United States, and the
      number of cases is expected to continue to rise worldwide. Cancer prevention
      strategies are crucial for reducing the cancer burden. The carcinogenic potential
      of dietary acrylamide exposure from cooked foods is unknown. Acrylamide is a by
      product of the common Maillard reaction where reducing sugars (i.e., fructose and
      glucose) react with the amino acid, asparagine. Based on the evidence of
      acrylamide carcinogenicity in animals, the International Agency for Research on
      Cancer has classified acrylamide as a group 2A carcinogen for humans. Since the
      discovery of acrylamide in foods in 2002, a number of studies have explored its
      potential as a human carcinogen. This article outlines a systematic review of
      dietary acrylamide and human cancer, acrylamide exposure and internal dose,
      exposure assessment methods in the epidemiologic studies, existing data gaps, and
      future directions. A majority of the studies reported no statistically
      significant association between dietary acrylamide intake and various cancers,
      and few studies reported increased risk for renal, endometrial, and ovarian
      cancers; however, the exposure assessment has been inadequate leading to
      potential misclassification or underestimation of exposure. Future studies with
      improved dietary acrylamide exposure assessment are encouraged. 

PMID- 24875405
TI  - Effects of vaginal lactobacilli in Chlamydia trachomatis infection.
AB  - Increasing evidence indicates that abnormal vaginal flora lacking lactobacilli
      facilitates the acquisition of several sexually transmitted diseases including
      Chlamydia trachomatis. C. trachomatis, the most common bacterial agent of genital
      infections worldwide, can progress from the lower to upper reproductive tract and
      induce severe sequelae. The ability of C. trachomatis to develop into a
      persistent form has been suggested as key pathogenetic mechanism underlying
      chronic infections and sequelae. The aim of our study was to investigate the C.
      trachomatis interaction with vaginal microbiota analyzing the effects of
      Lactobacillus strains (L. brevis and L. salivarius) on the different phases of C.
      trachomatis developmental cycle. In addition, the effect of lactobacilli on
      persistent chlamydial forms induced by HSV-2 coinfection has also been evaluated.
      Our results demonstrated significant inhibition of C. trachomatis multiplication
      by vaginal lactobacilli. L. brevis was significantly more effective than L.
      salivarius (p<0.05) on all the steps of chlamydial infection cycle suggesting
      that the ability of lactobacilli to protect from infection is strain-dependent.
      Lactobacilli had an adverse effect on elementary chlamydial bodies (p<0.05), on
      chlamydial adsorption to epithelial cells (p<0.001) and on intracellular phases
      of chlamydial replication (p<0.0001). Our study also demonstrated a protective
      effect of lactobacilli toward persistent C. trachomatis forms induced by HSV-2
      coinfection. A significant increase in the production of C. trachomatis
      infectious progeny was observed in C. trachomatis/HSV-2 coinfection in the
      presence of L. brevis (p=0.01) despite a significant inhibition of C. trachomatis
      multiplication (p=0.028). Our data suggest that a healthy vaginal microbiota can
      reduce the risk of acquiring C. trachomatis infection and counteract the
      development of persistent chlamydial forms. 

PMID- 24875406
TI  - How graphene is expected to impact neurotherapeutics in the near future.
AB  - The scientific research on graphene, a monolayer honeycomb lattice made of carbon
      atoms which was initially isolated in 2004, has grown exponentially in the last
      decade. The increasing amount of research funding directed to basic science
      studies on such revolutionary material promises to boost the scientific
      discoveries and technological developments in such field in an unprecedented way.
      Because its unique mechanical, optical, thermal, electronic and magnetic
      properties, graphene research is expected to foster new technological
      developments with significant applications to neurotherapeutics in several
      different fields in the near future. However, before the advances on graphene
      research may reach the clinical practice, future studies on the biocompatibility,
      neurotoxicity as well as long-term effects of distinct graphene forms (as well as
      graphene's derivatives) upon different biological tissues are still required. 

PMID- 24875404
TI  - Spatial regulation of Aurora A activity during mitotic spindle assembly requires
      RHAMM to correctly localize TPX2.
AB  - Construction of a mitotic spindle requires biochemical pathways to assemble
      spindle microtubules and structural proteins to organize these microtubules into
      a bipolar array. Through a complex with dynein, the receptor for hyaluronan
      mediated motility (RHAMM) cross-links mitotic microtubules to provide structural
      support, maintain spindle integrity, and correctly orient the mitotic spindle.
      Here, we locate RHAMM to sites of microtubule assembly at centrosomes and non
      centrosome sites near kinetochores and demonstrate that RHAMM is required for the
      activation of Aurora kinase A. Silencing of RHAMM delays the kinetics of spindle
      assembly, mislocalizes targeting protein for XKlp2 (TPX2), and attenuates the
      localized activation of Aurora kinase A with a consequent reduction in mitotic
      spindle length. The RHAMM-TPX2 complex requires a C-terminal basic leucine zipper
      in RHAMM and a domain that includes the nuclear localization signal in TPX2.
      Together, our findings identify RHAMM as a critical regulator for Aurora kinase A
      signaling and suggest that RHAMM ensures bipolar spindle assembly and mitotic
      progression through the integration of biochemical and structural pathways. 

PMID- 24875407
TI  - Parathyroid hormone as a marker for metabolic bone disease of prematurity.
AB  - OBJECTIVE: To compare parathyroid hormone to alkaline phosphatase as a serologic
      marker for metabolic bone disease (MBD) in preterm infants. STUDY DESIGN: An 18
      month prospective observational study in neonates with birth weight < 1250 g.
      Simultaneous serum parathyroid hormone (PTH), alkaline phosphatase (ALP), calcium
      (Ca) and phosphorus (P) were measured at scheduled intervals during
      hospitalization. At 6 weeks of age, MBD was evaluated using knee radiographs.
      Comparisons were analyzed using multivariate logistic regression, receiver
      operating characteristic (ROC) curves, chi2 and Student t-test. RESULT: Fourty
      nine infants were included in the study: 7 with severe and 42 with mild MBD.
      Using ROC curves, at 660 U l-1 ALP had a sensitivity of 29% and specificity of
      93% for severe MBD, while a cutoff point of 180 pg ml-1 gave PTH a sensitivity of
      71% and specificity of 88%. Infants with severe bone disease had a lower birth
      weight, 21-day serum P, an increased use of glucocorticoids and caffeine, and
      more likely to have major neonatal morbidities. CONCLUSION: PTH is an early
      marker with better sensitivity than ALP in screening for MBD. At 3 weeks
      chronologic age, a PTH level > 180 mg dl-1 or a P level <4.6 pg ml-1 yielded a
      sensitivity of 100% and specificity of 94% for severe MBD [corrected].

PMID- 24875408
TI  - Factors affecting nasal intermittent positive pressure ventilation failure and
      impact on bronchopulmonary dysplasia in neonates.
AB  - BACKGROUND: Nasal intermittent positive pressure ventilation (NIPPV) is becoming
      more important as a mode of ventilation in premature neonates predisposed to
      development of bronchopulmonary dysplasia (BPD). To the best of our knowledge,
      there have been no detailed studies characterizing neonates who fail NIPPV.
      OBJECTIVE: To determine the differences between neonates who are successfully
      extubated to NIPPV and those who require re-intubation from NIPPV, and the impact
      of timing of NIPPV failure on BPD rates. STUDY DESIGN: This was a retrospective
      cohort study in which we included infants with gestational age (GA) ? 28 weeks
      and birth weight ? 1000 g. chi2-test, analysis of variance and multivariate
      logistic regression models were used. RESULTS: Two hundred and forty infants were
      studied; 180 failed NIPPV and of those, 33 (18%), 39 (22%) and 108 (60%) failed
      NIPPV within 0 to 6 h, ? 6 to 24 h and ? 24 h, respectively. Female sex and
      increased weight were protective against NIPPV failure (adjusted odds ratio (95%
      confidence interval): 0.28 (0.14 to 0.58), 0.04 (0.01 to 0.22)). Increased GA at
      extubation and female sex were both associated with increased time to failure
      (P=0.008, <0.001, respectively). Apnea was more likely the cause for failure ? 24
      h (P=0.015), whereas increased work of breathing/fraction of inspired oxygen
      requirements were more significant when NIPPV failure occurred earlier (P=0.001).
      Neonates who failed NIPPV within 24 h did not have any association with
      likelihood of developing BPD or severity of BPD, after adjusting for confounding
      variables. CONCLUSION: Significant differences in neonatal characteristics may
      help identify which neonates are more likely to fail NIPPV, and their timing of
      failure.

PMID- 24875409
TI  - Mode of delivery in pregnancies complicated by major fetal congenital heart
      disease: a retrospective cohort study.
AB  - OBJECTIVE: To determine the mode of delivery in pregnancies complicated by
      complex fetal congenital heart disease (CHD). STUDY DESIGN: Five-year
      retrospective cohort study at a tertiary fetal medicine center (2007 to 2011).
      Cases of complex fetal CHD (n=126) were compared with 45 069 non-anomalous
      singleton infants ?500 g to determine rates of emergency intrapartum cesarean
      section (CS), preterm delivery and induction of labor. RESULT: Intrapartum CS is
      significantly higher in fetal CHD than non-anomalous controls (21% vs 13.5%, odds
      ratio (OR) 1.7, 95% confidence interval (CI): 1.0 to 2.7; P=0.035), predominantly
      related to CS for non-reassuring fetal status (OR 2.2, 95% CI: 1.1 to 4.1;
      P=0.022). Although fetal CHD did not increase emergency CS rates in nulliparous
      women, CS was significantly increased in multiparous pregnancies (OR 2.4, 95% CI:
      1.8 to 4.6; P=0.014). Rates of preterm delivery (OR 3.4, 95% CI: 2.0 to 5.4;
      P<0.0001) and induction of labor (OR 1.9, 95% CI: 1.3 to 2.9; P=0.001) were
      higher in the CHD cases. CONCLUSION: Emergency CS is increased in fetal CHD,
      attributed to a higher rate of CS for non-reassuring fetal status and seen mostly
      in multiparous women.

PMID- 24875410
TI  - The utilization of circulating cell-free fetal DNA testing and decrease in
      invasive diagnostic procedures: an institutional experience.
AB  - OBJECTIVE: To characterize the patient population utilizing circulating cell-free
      fetal DNA (ccffDNA) testing at a large academic center and evaluate trends in the
      performance of invasive diagnostic procedures. STUDY DESIGN: A retrospective
      cohort study of all patients who underwent cell-free DNA testing from May to
      December 2012 was performed. RESULT: During the study period, 206 patients had
      cell-free DNA testing. Of those, 75% (155/206) were of ages ? 35 years. Of those
      undergoing ccffDNA testing, 41% had positive aneuploidy screening and 38% had
      abnormal ultrasound findings. Only 7% of the patients with negative ccffDNA
      testing opted for an invasive diagnostic procedure compared with 60% with
      positive testing (P<0.01). The rate of invasive procedures decreased from 5.9% of
      all visits to the center during a similar 8-month period in 2010 to 4.1% of all
      visits during the study period (P<0.01). CONCLUSION: Our data suggest that
      ccffDNA testing leads to reduced uptake of invasive procedures.

PMID- 24875411
TI  - Severe perineal laceration during operative vaginal delivery: the impact of
      occiput posterior position.
AB  - OBJECTIVE: To identify risk factors for severe (third/fourth degree) perineal
      laceration with operative vaginal delivery (OVD, forceps or vacuum). STUDY
      DESIGN: Case-control study comparing singleton OVDs with or without severe
      laceration (n=138). RESULT: In multivariable analyses, severe perineal laceration
      was associated with occiput posterior (OP) position at delivery, vaginal
      nulliparity, use of forceps, longer period pushing in the second stage and lower
      gestational age, but not birth weight, labor induction or episiotomy. Among 29 OP
      patients at full dilation, 9/13 (69%) attempted rotations to occiput anterior
      (OA) were successful, and 14/16 (88%) patients in whom rotation was not attempted
      remained OP at delivery. Successful rotation from OP to OA was associated with
      fewer severe lacerations than no attempt or unsuccessful rotation (22 vs 75%,
      P=0.01). CONCLUSION: Severe perineal laceration during OVD is associated with OP
      position at delivery and is reduced threefold in patients successfully rotated
      from OP to OA.

PMID- 24875414
TI  - Genetic predisposition to left ventricular dysfunction: a multigenic and multi
      analytical approach.
AB  - BACKGROUND: Left ventricular dysfunction (LVD) is a complex, multifactorial
      condition, caused by mechanical, neurohormonal, and genetic factors. We have
      previously observed association of renin-angiotensin-aldosterone system (RAAS),
      matrix metalloproteinases (MMPs) and inflammatory pathway genes with LVD.
      Therefore the present study was undertaken to identify the combination of genetic
      variants and their possible interactions contributing towards genetic
      susceptibility to LVD in the background of coronary artery disease (CAD). METHODS
      AND RESULTS: The study included 230 healthy controls and 510 consecutive patients
      with angiographically confirmed CAD. Among them, 162 with reduced left ventricle
      ejection fraction (LVEF<=45%) were categorized as having LVD. We analyzed 11
      polymorphisms of RAAS, MMPs and inflammatory pathways. Single locus analysis
      showed that AT1 A1166C (p value<0.001; OR=3.67), MMP9 R668Q (p value=0.007;
      OR=3.48) and NFKB1-94 ATTG ins/del (p value=0.013; OR=2.01) polymorphisms were
      independently associated with LVD when compared with both non-LVD patients and
      healthy controls. High-order gene-gene interaction analysis, using classification
      and regression tree (CART) and multifactor dimensionality reduction (MDR)
      revealed that AT1 A1166C and NFKB1-94 ATTG ins/del polymorphisms jointly
      increased the risk of LVD to great extent (p-value=0.001; OR=8.55) and best four
      factor interaction model consisted of AT1 A1166C, MMP7 A-181G, MMP9 R668Q and
      NFKB1-94 ATTG ins/del polymorphisms with testing accuracy of 0.566 and cross
      validation consistency (CVC)=9/10 (permutation p<0.001) showed increased risk for
      LVD respectively. CONCLUSION: AT1 A1166C independently and in combination with
      MMP9 R668Q and NFKB1-94 ATTG ins/del polymorphisms plays important role in
      conferring genetic susceptibility to LVD in CAD patients.

PMID- 24875415
TI  - Fluctuation of Dof1/Dof2 expression ratio under the influence of varying nitrogen
      and light conditions: involvement in differential regulation of nitrogen
      metabolism in two genotypes of finger millet (Eleusine coracana L.).
AB  - In order to gain insights into the mechanism of high nitrogen use efficiency
      (NUE) of finger millet (FM) the role of Dof2 transcription factor (TF), which is
      a repressor of genes involved in C/N metabolism was investigated. The partial
      cDNA fragment of EcDof2 (912-bp; GenBank acc. no. KF261117) was isolated and
      characterized from finger millet (FM) that showed 63% and 58% homology with Dof2
      of Zea mays at nucleotide and protein level, respectively. Its expression studies
      were carried out along with the activator EcDof1 in two genotypes (GE3885, high
      protein genotype (HPG); GE1437, low protein genotype (LPG)) of FM differing in
      grain protein contents (13.8% and 6.2%) showed that EcDof2 is expressed in both
      shoot and root tissues with significantly (p<=0.05) higher expression in the
      roots. The diurnal expression of both EcDof1 and EcDof2 in shoots was
      differential having different time of peak expression indicating a differential
      response to diurnal condition. Under continuous dark conditions, expression of
      EcDof1 and EcDof2 oscillated in both the genotypes whereas on illumination, the
      fold expression of EcDof1 was higher as compared to EcDof2. Under increasing
      nitrate concentration, EcDof2 expression increases in roots and shoots of LPG
      while it remains unchanged in HPG. However, the EcDof1 expression was found to
      increase in both genotypes. Further, time kinetics studies under single nitrate
      concentration revealed that EcDof2 was repressed in the roots of both genotypes
      whereas EcDof1 oscillated with time. The EcDof1/EcDof2 ratio measured showed
      differential response under different light and nitrogen conditions. It was
      higher in the roots of HPG indicating higher activation of genes involved in N
      uptake and assimilation resulting in high grain protein accumulation. The results
      indicate that both light and nitrogen concentration influence Dof1 and Dof2
      expression and suggests a complex pattern of regulation of genes influenced by
      these plant specific TFs. In nutshell, the Dof1/Dof2 ratio can serve as an index
      for measuring the N responsiveness and NUE of crops and can be further validated
      by Dof2 knock down approach. 

PMID- 24875416
TI  - Transcriptome analysis of grain-filling caryopses reveals the potential formation
      mechanism of the rice sugary mutant.
AB  - A sugary mutant with low total starch and high sugar contents was compared with
      its wild type Sindongjin for grain-filling caryopses. In the present study,
      developing seeds of Sindongjin and sugary mutant from the 11th day after
      flowering (DAF) were subjected to RNA sequencing (RNA-Seq). A total of 30,385 and
      32,243 genes were identified in Sindongjin and sugary mutant. Transcriptomic
      change analysis showed that 7713 differentially expressed genes (DEGs) (log2 fold
      change >=1, false discovery rate (FDR)<=0.001) were identified based on our RNA
      Seq data, with 7239 genes up-regulated and 474 down-regulated in the sugary
      mutant. A large number of DEGs were found related to metabolic, biosynthesis of
      secondary metabolites, plant-pathogen interaction, plant hormone signal
      transduction and starch/sugar metabolism. Detailed pathway dissection and
      quantitative real time PCR (qRT-PCR) demonstrated that most genes involved in
      sucrose to starch synthesis are up-regulated, whereas the expression of the ADP
      glucose pyrophosphorylase small subunit (OsAGPS2b) catalyzing the first committed
      step of starch biosynthesis was specifically inhibited during the grain-filling
      stage in sugary mutant. Further analysis suggested that the OsAGPS2b is a
      considerable candidate gene responsible for phenotype of sugary mutant.

PMID- 24875417
TI  - Molecular cloning and expression analysis of the sucrose transporter gene family
      from Theobroma cacao L.
AB  - In this study, we performed cloning and expression analysis of six putative
      sucrose transporter genes, designated TcSUT1, TcSUT2, TcSUT3, TcSUT4, TcSUT5 and
      TcSUT6, from the cacao genotype 'TAS-R8'. The combination of cDNA and genomic DNA
      sequences revealed that the cacao SUT genes contained exon numbers ranging from 1
      to 14. The average molecular mass of all six deduced proteins was approximately
      56 kDa (range 52 to 66 kDa). All six proteins were predicted to exhibit typical
      features of sucrose transporters with 12 trans-membrane spanning domains.
      Phylogenetic analysis revealed that TcSUT2 and TcSUT4 belonged to Group 2 SUT and
      Group 4 SUT, respectively, and the other TcSUT proteins were belonging to Group 1
      SUT. Real-time PCR was conducted to investigate the expression pattern of each
      member of the SUT family in cacao. Our experiment showed that TcSUT1 was
      expressed dominantly in pods and that, TcSUT3 and TcSUT4 were highly expressed in
      both pods and in bark with phloem. Within pods, TcSUT1 and TcSUT4 were expressed
      more in the seed coat and seed from the pod enlargement stage to the ripening
      stage. TcSUT5 expression sharply increased to its highest expression level in the
      seed coat during the ripening stage. Expression pattern analysis indicated that
      TcSUT genes may be associated with photoassimilate transport into developing
      seeds and may, therefore, have an impact on seed production.

PMID- 24875418
TI  - Cytoplasmic effects on DNA methylation between male sterile lines and the
      maintainer in wheat (Triticum aestivum L.).
AB  - Male sterile cytoplasm plays an important role in hybrid wheat, and three-line
      system including male sterile (A line), its maintainer (B line) and restoring (R
      line) has played a major role in wheat hybrid production. It is well known that
      DNA methylation plays an important role in gene expression regulation during
      biological development in wheat. However, no reports are available on DNA
      methylation affected by different male sterile cytoplasms in hybrid wheat. We
      employed a methylation-sensitive amplified polymorphism technique to characterize
      nuclear DNA methylation in three male sterile cytoplasms. A and B lines share the
      same nucleus, but have different cytoplasms which is male sterile for the A and
      fertile for the B. The results revealed a relationship of DNA methylation at
      these sites specifically with male sterile cytoplasms, as well as male sterility,
      since the only difference between the A lines and B line was the cytoplasm. The
      DNA methylation was markedly affected by male sterile cytoplasms. K-type
      cytoplasm affected the methylation to a much greater degree than T-type and S
      type cytoplasms, as indicated by the ratio of methylated sites, ratio of fully
      methylated sites, and polymorphism between A lines and B line for these
      cytoplasms. The genetic distance between the cytoplasm and nucleus for the K-type
      is much greater than for the T- and S-types because the former is between
      Aegilops genus and Triticum genus and the latter is within Triticum genus between
      Triticum spelta and Triticum timopheevii species. Thus, this difference in
      genetic distance may be responsible for the variation in methylation that we
      observed.

PMID- 24875419
TI  - Functional sequence variants within the SIRT1 gene promoter in indirect inguinal
      hernia.
AB  - Inguinal hernia is a common surgical disease, for which genetic factors have been
      suggested to play a role. Sirtuin 1 (SIRT1), a highly conserved NAD-dependent
      class III deacetylase, has been implicated in human diseases. Since SIRT1
      regulates differentiation and proliferation of human skeletal muscles and
      fibroblasts, we speculated that misregulation of SIRT1 gene, caused by DNA
      sequence variants (DSVs) within its regulatory regions, may contribute to
      inguinal hernia development. In this study, SIRT1 gene promoter was genetically
      and functionally analyzed in patients with indirect inguinal hernia (IIH) (n=139)
      and ethnic-matched healthy controls (n=148). Two heterozygous DSVs, g.69644213G>A
      and g.69644268T>A, and one single nucleotide polymorphism (SNP), g.69643707A>C
      (rs35706870), were found in IIH patients, but not in controls. Two closely-linked
      SNPs, g.69644217A>C (rs932658) and g.69644341G>C (rs2394443), were found in IIH
      patients with significantly higher frequency, compared to controls (P=0.006). The
      C alleles of the SNPs g.69644217A>C (rs932658) and g.69644341G>C (rs2394443) were
      associated with IIH (P=0.028, OR 1.600, 95%CI 1.049-2.439). These DSVs
      significantly altered the transcriptional activities of the SIRT1 gene promoter
      in cultured cells. Therefore, our data suggested that these DSVs may alter the
      transcriptional activities of SIRT1 gene promoter and change SIRT1 levels,
      contributing to IIH development as risk factors.

PMID- 24875420
TI  - Simple and compact optode for real-time in-situ temperature detection in very
      small samples.
AB  - Real-time in-situ temperature detection is essential in many applications. In
      this paper, a simple and robust optode, which uses Ruthenium (II) complex as a
      temperature indicator, has been developed for rapid and sensitive temperature
      detection in small volume samples (<5 MUL). Transmission of excitation light and
      collection and transmission of fluorescence are performed by a homemade single
      multi mode fiber coupler, which provides the entire system with a simple and
      robust structure. The photoluminescence intensity of Ruthenium (II) complex
      diminishes monotonically from 0 degrees C to 80 degrees C, and the response to
      temperature is rapid and completely reversible. When temperature is less than (or
      higher than) 50 degrees C, a linear correlation exists between the fluorescence
      intensity and the temperature. Excellent agreement was also observed between the
      continuous and in situ measurements obtained by the presented optode and the
      discrete temperature values measured by a conventional thermometer. The proposed
      optode has high sensitivity, high photostability and chemical stability, a wide
      detection range, and thermal reversibility, and can be applied to real-time in
      situ temperature detection of a very small volume biological, environmental, and
      chemical sample.

PMID- 24875421
TI  - Candida albicans cis-prenyltransferase Rer2 is required for protein
      glycosylation, cell wall integrity and hypha formation.
AB  - cis-Prenyltransferase is the first enzyme of the mevalonate pathway committed to
      the biosynthesis of dolichol in eukaryotes. The RER2 gene encoding cis
      prenyltransferase (Rer2p) in the human fungal pathogen Candida albicans was
      characterized. In addition, the ORF19.5236 encoding the second cis
      prenyltransferase, which putatively is responsible for the synthesis of longer
      polyisoprenoids chains, was identified. When cultivated under repressive
      conditions, the conditional mutant strain expressing the RER2 gene from the
      regulatable MET3 promoter contained only 4% of cis-prenyltransferase activity and
      markedly diminished amounts of dolichols, as compared to the wild-type strain.
      Moreover, transcriptomal analyses revealed changes in the expression of 300
      genes, mainly involved in transport, response to stress, filamentous growth and
      organelle organization. Growth of the conditional strain was blocked completely
      at 37  degrees C. The strain was hypersensitive to a wide range of inhibitors,
      which suggested glycosylation defects and compromised cell wall integrity.
      Moreover, the rer2 conditional mutant grown in the repressive conditions, unlike
      the same strain in the absence of repressor, failed to form hyphae. The results
      indicate that dolichols are essential not only for protein glycosylation and cell
      wall integrity but also for growth and development of C. albicans.

PMID- 24875422
TI  - Role of MoAND1-mediated nuclear positioning in morphogenesis and pathogenicity in
      the rice blast fungus, Magnaporthe oryzae.
AB  - To cause disease on host plants, many phytopathogenic fungi undergo morphological
      transitions including development of reproductive structures as well as
      specialized infection structures called appressoria. Such morphological
      transitions display distinct nuclear dynamics. Here we report the developmental
      requirement of MoAND1-mediated nuclear positioning for pathogenesis of the rice
      blast fungus, Magnaporthe oryzae. The MoAND1 gene encodes a protein that shows
      high similarity to Num1 in Saccharomyces cerevisiae and ApsA in Aspergillus
      nidulans, both of which are cell cortex proteins involved in nuclear migration
      and positioning. Targeted deletion of MoAND1 did not affect radial growth of the
      fungus but impaired nuclear distribution along the hyphae, which is reminiscent
      of ApsA mutant. In contrast to the wild-type, which produces three to five spores
      in a sympodial manner on the conidiophore, only a single spore was borne on the
      conidiophore of DeltaMoand1, resulting in ~65% decrease in conidia production,
      compared to the wild-type. The mutant conidia displayed abnormalities in
      septation pattern and nuclear distribution, which were correlated with their
      inability to germinate. Spores of the mutant that did germinate were capable of
      differentiating appressoria but were defective in the execution of programmed
      nuclear migration and positioning during development. Furthermore, mutant
      appressoria were not fully functional, leading to delay in penetration of host
      plants. However, the ability of DeltaMoand1 to grow inside host tissues was
      comparable to that of the wild-type. All these defects greatly decreased the
      virulence of the mutant. Taken together, our data suggest that there is a
      stringent but incomplete developmental requirement for proper migration and
      positioning of fungal nuclei mediated by MoAND1 during asexual reproduction and
      pre-penetration phase of fungal pathogenesis. 

PMID- 24875423
TI  - The HAP complex in Fusarium verticillioides is a key regulator of growth,
      morphogenesis, secondary metabolism, and pathogenesis.
AB  - Among eukaryotic organisms, the HAP complex is a conserved, multimeric
      transcription factor that regulates gene expression by binding to the consensus
      sequence CCAAT. In filamentous fungi, the HAP complex has been linked to primary
      and secondary metabolism, but its role in pathogenesis has not been investigated
      extensively. The overarching goal of this study was to elucidate the role of the
      HAP complex in Fusariumverticillioides, a ubiquitous and damaging pathogen of
      maize. To this end, orthologs of core HAP complex genes (FvHAP2, FvHAP3, and
      FvHAP5) were identified and deleted in F. verticillioides via a reverse genetics
      approach. Deletion of FvHAP2, FvHAP3, or FvHAP5 resulted in an indistinguishable
      phenotype among the deletion strains, including reduced radial growth and
      conidiation, altered colony morphology, and derepression of pigmentation.
      Additionally, disruption of the HAP complex impaired infection and colonization
      of maize stalks. Deletion strains were hypersensitive to osmotic and oxidative
      stress, which suggests the HAP complex of F. verticillioides may mediate
      responses to environmental stress during pathogenesis. This study directly
      implicates the HAP complex in primary and secondary metabolism in F.
      verticillioides and provides one of the first links between the HAP complex and
      virulence in a plant pathogenic fungus. 

PMID- 24875424
TI  - Alpbach special issue.

PMID- 24875425
TI  - Physical size associations to offensive performance among major league leaders.
AB  - Minimal work has studied physical size effects on statistical performance among
      Major League players. In this study, longitudinal, bivariate, and regression
      analyses studied the impact of physical size on offensive baseball statistics
      within a homogeneous talent sample of Major League batting leaders. Body mass
      index (BMI) was calculated from heights and weights that were publicly available
      to form a statistical database of 4,360 offense leaders from 1950 to 2010.
      Repeated-measures analysis of variances examined differences in anthropometrics
      and baseball statistics between each decade from 1950 to 2010. Bivariate
      correlation and linear regression analyses evaluated BMI as an independent
      variable of influence, where all tests applied an a priori significance level (p
      <= 0.05). After 1980, offensive performance increased (p <= 0.05) concurrent to
      body mass and BMI growth (p < 0.001). During the 1960s, only batting average and
      on-base plus slugging percentages were found statistically decreased (p <= 0.05).
      All baseball statistics were positively correlated and predicted by BMI (p <
      0.001). Consideration to covariant factors is required in data interpretation,
      yet nonetheless, our results showed physical size (BMI) to positively influence
      Major League offensive statistics. Over the 60-year period, greater body weight
      to-height proportions owed to improved competitive performance, which suggests
      greater emphasis on hypertrophic stimuli in training and nutrition, as well as
      selection of larger professional baseball prospects.

PMID- 24875426
TI  - Contribution of strength characteristics to change of direction and agility
      performance in female basketball athletes.
AB  - Research has often examined the relationship between 1 or 2 measures of strength
      and change of direction (COD) ability reporting inconsistent relationships to
      performance. These inconsistencies may be the result of the strength assessment
      used and the assumption that 1 measure of strength can represent all "types" of
      strength required during a COD task. Therefore the purpose of this study was to
      determine the relationship between several lower-body strength and power
      measures, COD, and agility performance. Twelve (n = 12) elite female basketball
      athletes completed a maximal dynamic back squat, isometric midthigh pull,
      eccentric and concentric only back squat, and a countermovement jump, followed by
      2 COD tests (505 and T-test) and a reactive agility test. Pearson product-moment
      correlation and stepwise regression analysis were performed on all variables. The
      percentage contribution of each strength measure to an athletes total strength
      score was also determined. Our results demonstrated that both COD tests were
      significantly correlated to maximal dynamic, isometric, concentric, and eccentric
      strength (r = -0.79 to -0.89), with eccentric strength identified as the sole
      predictor of COD performance. Agility performance did not correlate with any
      measure of strength (r = -0.08 to -0.36), whereas lower-body power demonstrated
      no correlation to either agility or COD performance (r = -0.19 to -0.46). These
      findings demonstrate the importance of multiple strength components for COD
      ability, highlighting eccentric strength as a deterministic factor of COD
      performance. Coaches should aim to develop a well-rounded strength base in
      athletes; ensuring eccentric strength is developed as effectively as the often
      emphasized concentric or overall dynamic strength capacity.

PMID- 24875427
TI  - Allometric scaling of strength scores in NCAA division I-A football athletes.
AB  - This study examined population-specific allometric exponents to control for the
      effect of body mass (BM) on bench press, clean, and squat strength measures among
      Division I-A collegiate football athletes. One repetition maximum data were
      obtained from a university pre-season football strength assessment (bench press,
      n = 207; clean, n = 88; and squat n = 86) and categorized into 3 groups by
      positions (line, linebacker, and skill). Regression diagnostics and correlations
      of scaled strength data to BM were used to assess the efficacy of the allometric
      scaling model and contrasted with that of ratio scaling and theoretically based
      allometric exponents of 0.67 and 0.33. The log-linear regression models yielded
      the following exponents (b): b = 0.559, 0.287, and 0.496 for bench press, clean,
      and squat, respectively. Correlations between bench press, clean, and squat to BM
      were r = -0.024, -0.047, and -0.018, respectively, suggesting that the derived
      allometric exponents were effective in partialling out the effect of BM on these
      lifts and removing between-group differences. Conversely, unscaled, ratio-scaled,
      and allometrically scaled (b = 0.67 or 0.33) data resulted in significant
      differences between groups. It is suggested that the exponents derived in the
      present study be used for allometrically scaling strength measures in National
      Collegiate Athletic Association Division I-A football athletes. Use of the
      normative percentile rank scores provide coaches and trainers with a valid means
      of judging the effectiveness of their training programs by allowing comparisons
      between individuals without the confounding influence of BM.

PMID- 24875428
TI  - Hydration profile and sweat loss perception of male and female division II
      basketball players during practice.
AB  - Hydration affects multiple aspects of basketball performance, but few
      investigations have examined the hydration profiles of collegiate basketball
      players. We examined multiday prepractice hydration status of 11 male and 11
      female NCAA (National Collegiate Athletic Association) Division II basketball
      players' sweat losses, fluid intake, and how accurately players estimated their
      sweat losses. Urine-specific gravity (USG) was spontaneously assessed before 2
      practices. Sweat losses and fluid intakes were measured during a conditioning
      practice (CP) and sport-specific practice (SP). After practices, players filled
      1,030 ml practice bottles to estimate their sweat losses. Urine-specific gravity
      between practices exhibited a moderate correlation (r = 0.54; p = 0.012) and were
      consistently high (17% of samples = USG >1.030) with no difference in mean USG
      between men (1.026 +/- 0.004) and women (1.022 +/- 0.008). Athletes' estimations
      of their sweat loss volumes between CP and the longer SP were strongly correlated
      (r = 0.88; p < 0.001). Estimation error was high (absolute error for both
      practices = 71 +/- 52%) and error direction varied greatly within men. Women
      consistently underestimated sweat losses by 63 +/- 28% and 65 +/- 20% during CP
      and SP. Sweat losses during SP equaled 2,471 +/- 495 ml and 1,910 +/- 441 ml for
      men and women, respectively, but high practice fluid intake limited body mass
      losses to 1.1 +/- 0.6% by the end of practice. It is plausible that hypohydration
      is related to poor conceptualization of sweat losses. Simulating the methodology
      of this study could help identify chronically hypohydrated athletes and be used
      to educate on between-practice fluid needs.

PMID- 24875429
TI  - Visual tracking speed is related to basketball-specific measures of performance
      in NBA players.
AB  - The purpose of this study was to determine the relationship between visual
      tracking speed (VTS) and reaction time (RT) on basketball-specific measures of
      performance. Twelve professional basketball players were tested before the 2012
      13 season. Visual tracking speed was obtained from 1 core session (20 trials) of
      the multiple object tracking test, whereas RT was measured by fixed- and variable
      region choice reaction tests, using a light-based testing device. Performance in
      VTS and RT was compared with basketball-specific measures of performance (assists
      [AST]; turnovers [TO]; assist-to-turnover ratio [AST/TO]; steals [STL]) during
      the regular basketball season. All performance measures were reported per 100
      minutes played. Performance differences between backcourt (guards; n = 5) and
      frontcourt (forward/centers; n = 7) positions were also examined. Relationships
      were most likely present between VTS and AST (r = 0.78; p < 0.003), STL (r =
      0.77; p < 0.003), and AST/TO (r = 0.78; p < 0.003), whereas a likely relationship
      was also observed with TO (r = 0.49; p < 0.109). Reaction time was not related to
      any of the basketball-specific performance measures. Backcourt players were most
      likely to outperform frontcourt players in AST and very likely to do so for VTS,
      TO, and AST/TO. In conclusion, VTS seems to be related to a basketball player's
      ability to see and respond to various stimuli on the basketball court that
      results in more positive plays as reflected by greater number of AST and STL and
      lower turnovers.

PMID- 24875430
TI  - Erratum to: Gender and Race/Ethnicity Differences in Mental Health Care Use
      Before and During the Great Recession.

PMID- 24875432
TI  - Photoenhanced electrochemical interaction between Shewanella and a hematite
      nanowire photoanode.
AB  - Here we report the investigation of interplay between light, a hematite nanowire
      arrayed photoelectrode, and Shewanella oneidensis MR-1 in a solar-assisted
      microbial photoelectrochemical system (solar MPS). Whole cell electrochemistry
      and microbial fuel cell (MFC) characterization of Shewanella oneidensis strain MR
      1 showed that these cells cultured under (semi)anaerobic conditions expressed
      substantial c-type cytochrome outer membrane proteins, exhibited well-defined
      redox peaks, and generated bioelectricity in a MFC device. Cyclic voltammogram
      studies of hematite nanowire electrodes revealed active electron transfer at the
      hematite/cell interface. Notably, under a positive bias and light illumination,
      the hematite electrode immersed in a live cell culture was able to produce 150%
      more photocurrent than that in the abiotic control of medium or dead culture,
      suggesting a photoenhanced electrochemical interaction between hematite and
      Shewanella. The enhanced photocurrent was attributed to the additional redox
      species associated with MR-1 cells that are more thermodynamically favorable to
      be oxidized than water. Long-term operation of the hematite solar MPS with light
      on/off cycles showed stable current generation up to 2 weeks. Fluorescent optical
      microscope and scanning electron microscope imaging revealed that the top of the
      hematite nanowire arrays were covered by a biofilm, and iron determination
      colorimetric assay revealed 11% iron loss after a 10-day operation. To our
      knowledge, this is the first report on interfacing a photoanode directly with
      electricigens in a MFC system. Such a system could open up new possibilities in
      solar-microbial device that can harvest solar energy and recycle biomass
      simultaneously to treat wastewater, produce electricity, and chemical fuels in a
      self-sustained manner. 

PMID- 24875431
TI  - Borderline Personality Disorder and High Utilization of Inpatient Psychiatric
      Hospitalization: Concordance Between Research and Clinical Diagnosis.
AB  - The goals of this study were to (1) assess prevalence rates of borderline
      personality disorder (BPD) in public mental health patients and (2) compare
      research assessment rates to clinical record rates in those with and without a
      history of high utilization of inpatient psychiatric hospitalization. One hundred
      and sixty participants randomly selected from county mental health centers were
      fully assessed. Among the non-high utilizers, 10% met criteria for BPD on
      research diagnosis, 4.5% on clinical record diagnosis, and 1.5% on both. Among
      high utilizers, 42% met criteria for BPD on research diagnosis, 19% on clinical
      record diagnosis, and 19% on both. For the non-high utilizers, the sensitivity of
      the clinical record diagnosis (compared to the gold standard of the research
      diagnosis) was 15% and the specificity was 97%. For the high utilizer group, the
      sensitivity of the clinical record diagnosis was 45% and specificity was 100%
      indicating that there was never an incorrect clinical diagnosis of BPD among the
      high utilizers. Thus, while the specificity of the clinical record was high, the
      sensitivity of the clinical record diagnosis was quite low, and the clinical
      record greatly underestimated the prevalence of BPD in this sample. Further,
      since effective outpatient treatment has been developed for these expensive high
      utilizers with BPD, the under-recognition of BPD has significant implications for
      the planning of outpatient mental health services in public sector settings. 

PMID- 24875434
TI  - Effect of substrate provision on performance and behaviour of laying hens in the
      pecking and scratching area of furnished cages.
AB  - 1. An experiment was set up to study the effects of substrate provision on
      performance and behaviour in the pecking and scratching area (PSA) of non-beak
      trimmed hens housed in large furnished cages (60 hens/cage). 2. Three layer
      hybrids (two brown and one white, ISA-Hendrix Genetics, France) and two substrate
      conditions (with or without wheat bran automatically distributed on the PSA) were
      compared in a 3 * 2 experimental design with 12 cages per treatment. 3. Substrate
      distribution improved laying rate with no impact on the frequency of dirty or
      cracked eggs. 4. Substrate distribution improved the viability and body integrity
      of hens, which were not beak-trimmed. 5. Distribution of substrate tended to
      increase the number of hens in the PSA and enhanced their pecking and scratching
      behaviours but had a negative impact on the number of dust bath bouts per cage
      and encouraged dust bathing on the wire floor close to the feeder. 6. The white
      hens laid more eggs in the nest than the brown birds and used the PSA more for
      pecking, scratching and dust bathing at the end of the day than the brown hens,
      underlining the necessity to adapt cage furnishing and rearing management to
      specific behaviours of each layer genotype.

PMID- 24875436
TI  - Flaps, flaps, flaps: the evolution continues.

PMID- 24875435
TI  - Early morning awakening and nonrestorative sleep are associated with increased
      minor non-fatal accidents during work and leisure time.
AB  - BACKGROUND: The relationship between a composite measure of insomnia and
      occupational or fatal accidents has been investigated previously; however, little
      is known regarding the effect of various insomnia symptoms on minor non-fatal
      accidents during work and leisure time. OBJECTIVE: We investigated the predicting
      role of insomnia symptoms on minor non-fatal accidents during work and leisure
      time. METHODS: Data from the 2005 Taiwan Social Development Trend Survey of
      36,473 Taiwanese aged >=18 years were analyzed in 2013. Insomnia symptoms,
      including difficulty in initiating sleep (DIS), difficulty in maintaining sleep
      (DMS), early morning awakening (EMA), and nonrestorative sleep (NRS) were
      investigated. A minor non-fatal accident was defined as any mishap such as
      forgetting to turn off the gas or faucets, accidental falls, and abrasions or
      cuts occurring during work and leisure time in the past month that do not require
      immediate medical attention. Multivariable logistic regression was performed to
      assess the odds ratios (ORs) and associated 95% confidence interval (CI) of minor
      non-fatal accidents (as a binary variable) for each insomnia symptom compared
      with those of people presenting no symptoms, while controlling for possible
      confounders. RESULTS: EMA and NRS increased the odds of minor non-fatal accidents
      occurring during work and leisure time (adjusted OR=1.19, 95% CI=1.08-1.32 and
      adjusted OR=1.27, 95% CI=1.17-1.37, respectively). CONCLUSION: EMA and NRS are
      two symptoms that are significantly associated with an increased likelihood of
      minor non-fatal accidents during work and leisure time after adjusting for of a
      range of covariates.

PMID- 24875433
TI  - Evaluating the optimal timing of revascularisation in patients with transient ST
      segment elevation myocardial infarction: rationale and design of the TRANSIENT
      Trial.
AB  - Patients with chest pain and a prehospital ST-segment elevation myocardial
      infarction (STEMI) are preferably treated with immediate percutaneous coronary
      intervention (PCI). However, patients with normalization of symptoms and ST
      segment elevation upon hospital arrival (transient STEMI) received inconsistent
      therapy due to logistic reasons and the absence of evidence or explicit
      guidelines. In this trial, the optimal timing of coronary angiography and
      subsequent revascularisation is investigated in patients presenting with
      transient STEMI. In this prospective, multicentre, randomized controlled clinical
      trial, 142 consecutive patients with initially acute chest pain and STEMI, whose
      symptoms and ST-segment elevation resolve upon admission, are randomized to
      immediate intervention or a delayed intervention. Primary outcome is infarct size
      measured at 4 days determined by cardiovascular magnetic resonance. Secondary
      outcomes are left ventricular function and volumes, myocardial salvage and
      microvascular injury at baseline; the change in left ventricular function,
      volumes and infarct size at 4 months; and major adverse cardiac events at 4 and
      12 months. The TRANSIENT Trial evaluates whether a delayed invasive strategy
      (according to NSTEMI-guidelines) is superior to an immediate invasive strategy
      (according to STEMI-guidelines) in patients with a transient STEMI. 

PMID- 24875437
TI  - Functional reconstruction of a large anterior thigh defect using contralateral
      anterolateral thigh flap with tensor fasciae latae and motorized vastus
      lateralis.

PMID- 24875438
TI  - Autologous breast reconstruction: preoperative magnetic resonance angiography for
      perforator flap vessel mapping.
AB  - BACKGROUND: Selection of a vascular pedicle for autologous breast reconstruction
      is time consuming and depends on visual evaluation during the surgery.
      Preoperative imaging of donor site for mapping the perforator artery anatomy
      greatly improves the efficiency of perforator selection and significantly reduces
      the operative time. In this article, we present our experience with magnetic
      resonance angiography (MRA) for perforator vessel mapping including MRA technique
      and interpretation. METHODS: We have performed over 400 MRA examinations from
      August 2008 to August 2013 at our institution for preoperative imaging of donor
      site for mapping the perforator vessel anatomy. Using our optimized imaging
      protocol with blood pool magnetic resonance imaging contrast agents, multiple
      donor sites can be imaged in a single MRA examination. Following imaging using
      the postprocessing and reporting tool, we estimated incidence of commonly used
      perforators for autologous breast reconstruction. RESULTS: In our practice,
      anterior abdominal wall tissue is the most commonly used donor site for
      perforator flap breast reconstruction and deep inferior epigastric artery
      perforators are the most commonly used vascular pedicle. A thigh flap, based on
      the profunda femoral artery perforator has become the second most used flap at
      our institution. In addition, MRA imaging also showed evidence of metastatic
      disease in 4% of our patient subset. CONCLUSION: Our MRA technique allows the
      surgeons to confidently assess multiple donor sites for the best perforator and
      flap design. In conclusion, a well-performed MRA with specific postprocessing
      provides an accurate method for mapping perforator vessel, at the same time
      avoiding ionizing radiation.

PMID- 24875439
TI  - Water adsorption in MOFs: fundamentals and applications.
AB  - This review article presents the fundamental and practical aspects of water
      adsorption in Metal-Organic Frameworks (MOFs). The state of the art of MOF
      stability in water, a crucial issue to many applications in which MOFs are
      promising candidates, is discussed here. Stability in both gaseous (such as humid
      gases) and aqueous media is considered. By considering a non-exhaustive yet
      representative set of MOFs, the different mechanisms of water adsorption in this
      class of materials are presented: reversible and continuous pore filling,
      irreversible and discontinuous pore filling through capillary condensation, and
      irreversibility arising from the flexibility and possible structural
      modifications of the host material. Water adsorption properties of more than 60
      MOF samples are reported. The applications of MOFs as materials for heat-pumps
      and adsorbent-based chillers and proton conductors are also reviewed. Some
      directions for future work are suggested as concluding remarks. 

PMID- 24875440
TI  - Rationale and approaches to the prevention of smoking-related diseases: overview
      of recent studies on chemoprevention of smoking-induced tumors in rodent models.
AB  - Tobacco smoke plays a dominant role in the epidemiology of lung cancer, cancer at
      other sites, and a variety of other chronic diseases. It is the leading cause of
      death in developed countries, and the global burden of cancer is escalating in
      less developed regions. For a rational implementation of strategies exploitable
      for the prevention smoking-related diseases, it is crucial to elucidate both the
      mechanisms of action of cigarette smoke and the protective mechanisms of the host
      organism. The imperative primary prevention goal is to avoid any type of exposure
      to smoke. Epidemiological studies have shown that a decrease in the consumption
      of cigarettes can be successful in attenuating the epidemic of lung cancer in
      several countries. Chemoprevention by means of dietary and/or pharmacological
      agents provides a complementary strategy aimed at decreasing the risk of
      developing smoking-associated diseases in addicted current smokers, who are
      unable to quit smoking, and especially in involuntary smokers and ex-smokers. The
      availability of new animal models that are suitable to detect the carcinogenicity
      of cigarette smoke and to assess the underlying molecular mechanisms provides new
      tools for evaluating both safety and efficacy of putative chemopreventive agents.

PMID- 24875442
TI  - Environmental exposure to lead (Pb) and variations in its susceptibility.
AB  - Based on exposure frequency and intrinsic toxicity, lead (Pb) ranks one of the
      highest priority toxic materials. Continuous regulation of environmental Pb
      exposure has contributed to dramatically diminished exposure levels of Pb, for
      example, blood level of Pb. However, the safety level of Pb is not established,
      as low-level exposure to Pb still shows severe toxicity in high susceptible
      population and late onset of some diseases from early exposure. In the present
      study, we focused on food-borne Pb exposure and found broad variations in Pb
      exposure levels via food among countries. In addition, there are genetic or
      ethnical variations in Pb-targeted and protective genes. Moreover, various
      epigenetic alterations were induced by Pb poisoning. Therefore, we suggest a
      systemic approach including governmental (public) and individual prevention from
      Pb exposure with continuous biological monitoring and genetic or epigenetic
      consideration. 

PMID- 24875443
TI  - Enzyme-like activity of nanomaterials.
AB  - Due to possessing an extremely small size and a large surface area per unit of
      volume, nanomaterials have specific characteristic physical, chemical,
      photochemical, and biological properties that are very useful in many new
      applications. Nanoparticles' catalytic activity and intrinsic ability in
      generating or scavenging reactive oxygen species in general can be used to mimic
      the catalytic activity of natural enzymes. Many nanoparticles with enzyme-like
      activities have been found, potentially capable of being applied for commercial
      uses, such as in biosensors, pharmaceutical processes, and the food industry. To
      date, a variety of nanoparticles, especially those formed from noble metals, have
      been determined to possess oxidase-like, peroxidase-like, catalase-like, and/or
      superoxide dismutase-like activity. The ability of nanoparticles to mimic
      enzymatic activity, especially peroxidase mimics, can be used in a variety of
      applications, such as detection of glucose in biological samples and waste water
      treatment. To study the enzyme-like activity of nanoparticles, the electron spin
      resonance method represents a critically important and convenient analytical
      approach for zero-time detection of the reactive substrates and products as well
      as for mechanism determination. 

PMID- 24875444
TI  - A comparative analysis of the statistical properties of large mobile phone
      calling networks.
AB  - Mobile phone calling is one of the most widely used communication methods in
      modern society. The records of calls among mobile phone users provide us a
      valuable proxy for the understanding of human communication patterns embedded in
      social networks. Mobile phone users call each other forming a directed calling
      network. If only reciprocal calls are considered, we obtain an undirected mutual
      calling network. The preferential communication behavior between two connected
      users can be statistically tested and it results in two Bonferroni networks with
      statistically validated edges. We perform a comparative analysis of the
      statistical properties of these four networks, which are constructed from the
      calling records of more than nine million individuals in Shanghai over a period
      of 110 days. We find that these networks share many common structural properties
      and also exhibit idiosyncratic features when compared with previously studied
      large mobile calling networks. The empirical findings provide us an intriguing
      picture of a representative large social network that might shed new lights on
      the modelling of large social networks. 

PMID- 24875445
TI  - Collateral sensitivity of resistant MRP1-overexpressing cells to flavonoids and
      derivatives through GSH efflux.
AB  - The multidrug resistance protein 1 (MRP1) is involved in multidrug resistance of
      cancer cells by mediating drug efflux out of cells, often in co-transport with
      glutathione (GSH). GSH efflux mediated by MRP1 can be stimulated by verapamil. In
      cells overexpressing MRP1, we have previously shown that verapamil induced a huge
      intracellular GSH depletion which triggered apoptosis of the cells. That
      phenomenon takes place in the more global anticancer strategy called "collateral
      sensitivity" and could be exploited to eradicate some chemoresistant cancer
      cells. Seeking alternative compounds to verapamil, we screened a library of
      natural flavonoids and synthetic derivatives. A large number of these compounds
      stimulate MRP1-mediated GSH efflux and the most active ones have been evaluated
      for their cytotoxic effect on MRP1-overexpressing cells versus parental cells.
      Interestingly, some are highly and selectively cytotoxic for MRP1-cells, leading
      them to apoptosis. However, some others do not exhibit any cytotoxicity while
      promoting a strong GSH efflux, indicating that GSH efflux is necessary but not
      sufficient for MRP1-cells apoptosis. In support to this hypothesis, structure
      activity relationships show that the absence of a hydroxyl group at position 3 of
      the flavonoid C ring is an absolute requirement for induction of MRP1-cells
      death, but is not for GSH efflux stimulation. Chrysin (compound 8) and its
      derivatives, compounds 11 and 22, exhibit a high selectivity toward MRP1-cells
      with a IC50 value of 4.1 MUM for compound 11 and 4.9 MUM for chrysin and compound
      22, making them among the best described selective killer compounds of multidrug
      ABC transporter-overexpressing cells.

PMID- 24875447
TI  - An autophagic switch in the response of tumor cells to radiation and
      chemotherapy.
AB  - Four different functional forms of autophagy have been observed to occur in tumor
      cells in response to chemotherapeutic drugs and radiation. Currently the
      different forms of autophagy are distinguished almost exclusively by determining
      the impact of autophagy inhibition on drug and radiation sensitivity. That is, it
      cannot otherwise be predicted whether the autophagy induced by radiation or
      chemotherapy is associated with resistance and the circumstances under which
      autophagy inhibition might be a useful strategy for enhancing sensitivity to
      therapy. This commentary highlights an additional level of complexity in the
      autophagy landscape, specifically that autophagy can switch its function even
      within the context of a specific external stress and/or a biological cancer
      model.

PMID- 24875446
TI  - Assessment of the potential of polyphenols as a CYP17 inhibitor free of adverse
      corticosteroid elevation.
AB  - Inhibition of 17alpha-hydroxylase/17,20-lyase (CYP17), which dictates the
      proceeding of androgen biosynthesis, is recommended as an effective treatment for
      androgen-dependent diseases. However, androgen depletion by selective CYP17
      inhibition is accompanied with corticosteroid elevation, which increases risk of
      cardiovascular diseases. In this study, we evaluated the likelihood of
      polyphenols as a CYP17 inhibitor without cardiovascular complications. All
      examined polyphenols significantly inhibited CYP17 in human adrenocortical H295R
      cells, but their effects on androgen and cortisol biosynthesis were diverse.
      Resveratrol was the most potent CYP17 inhibitor with an approximate IC50 of 4
      MUM, and the inhibition might weigh on the 17alpha-hydroxylase activity more than
      the 17,20-lyase activity. Resveratrol also inhibited 21alpha-hydroxylase (CYP21)
      essential for corticosteroid biosynthesis but to a lesser extent, thus preventing
      the occurrence of cortisol elevation following CYP17 blockade. Although
      transcriptional down-regulation was important for alpha-naphthoflavone-mediated
      CYP17 inhibition, resveratrol inhibited CYP17 and CYP21 mainly at the level of
      enzyme activity rather than enzyme abundance and cytochrome P450 electron
      transfer. Daidzein also inhibited CYP17 and CYP21 although less potent than
      resveratrol. Daidzein was the only polyphenol showing inhibition of 3beta
      hydroxysteroid dehydrogenase type II (3betaHSD2). The exceptional 3betaHSD2
      inhibition led to dehydroepiandrosterone accumulation alongside daidzein-caused
      androgen biosynthetic impairment. In contrast, androgen and cortisol secretion
      was increased or remained normal under alpha-naphthoflavone and beta
      naphthoflavone treatments, suggesting that CYP17 inhibition was counteracted by
      increased substrate generation. alpha-naphthoflavone and beta-naphthoflavone also
      enhanced the formation of cortisol from 17-hydroxyprogesterone and testosterone
      from androstenedione. Our findings suggest a potential application of resveratrol
      in androgen deprivation therapy.

PMID- 24875441
TI  - Toxicogenomics and cancer susceptibility: advances with next-generation
      sequencing.
AB  - The aim of this review is to comprehensively summarize the recent achievements in
      the field of toxicogenomics and cancer research regarding genetic-environmental
      interactions in carcinogenesis and detection of genetic aberrations in cancer
      genomes by next-generation sequencing technology. Cancer is primarily a genetic
      disease in which genetic factors and environmental stimuli interact to cause
      genetic and epigenetic aberrations in human cells. Mutations in the germline act
      as either high-penetrance alleles that strongly increase the risk of cancer
      development, or as low-penetrance alleles that mildly change an individual's
      susceptibility to cancer. Somatic mutations, resulting from either DNA damage
      induced by exposure to environmental mutagens or from spontaneous errors in DNA
      replication or repair are involved in the development or progression of the
      cancer. Induced or spontaneous changes in the epigenome may also drive
      carcinogenesis. Advances in next-generation sequencing technology provide us
      opportunities to accurately, economically, and rapidly identify genetic variants,
      somatic mutations, gene expression profiles, and epigenetic alterations with
      single-base resolution. Whole genome sequencing, whole exome sequencing, and RNA
      sequencing of paired cancer and adjacent normal tissue present a comprehensive
      picture of the cancer genome. These new findings should benefit public health by
      providing insights in understanding cancer biology, and in improving cancer
      diagnosis and therapy. 

PMID- 24875450
TI  - Rhipicephalus (Boophilus) microplus tick in vitro feeding methods for functional
      (dsRNA) and vaccine candidate (antibody) screening.
AB  - Rhipicephalus (Boophilus) microplus (Acari: Ixodidae) ticks cause economic losses
      for cattle industries throughout tropical and subtropical regions of the world
      estimated at $US2.5 billion annually. Lack of access to efficacious long-lasting
      vaccination regimes and increases in tick acaricide resistance have led to the
      investigation of targets for the development of novel tick vaccines and
      treatments. In vitro tick feeding has been used for many tick species to study
      the effect of new acaricides on the transmission of tick-borne pathogens. Few
      studies have reported the use of in vitro feeding for functional genomic studies
      using RNA interference and/or the effect of specific anti-tick antibodies. In
      particular, in vitro feeding reports for the cattle tick are limited due to its
      relatively short hypostome. Previously published methods were further modified to
      broaden optimal tick sizes/weights, feeding sources including bovine and ovine
      serum, optimisation of commercially available blood anti-coagulant tubes, and IgG
      concentrations for effective antibody delivery. Ticks are fed overnight and
      monitored for ~5-6 weeks to determine egg output and success of larval emergence
      using a humidified incubator. Lithium-heparin blood tubes provided the most
      reliable anti-coagulant for bovine blood feeding compared with commercial
      citrated (CPDA) and EDTA tubes. Although >30mg semi-engorged ticks fed more
      reliably, ticks as small as 15mg also fed to repletion to lay viable eggs. Ticks
      which gained less than ~10mg during in vitro feeding typically did not lay eggs.
      One mg/ml IgG from Bm86-vaccinated cattle produced a potent anti-tick effect in
      vitro (83% efficacy) similar to that observed in vivo. Alternatively, feeding of
      dsRNA targeting Bm86 did not demonstrate anti-tick effects (11% efficacy)
      compared with the potent effects of ubiquitin dsRNA. This study optimises R.
      microplus tick in vitro feeding methods which support the development of cattle
      tick vaccines and treatments. 

PMID- 24875448
TI  - Sanguinarine suppresses basal-like breast cancer growth through dihydrofolate
      reductase inhibition.
AB  - Basal-like breast cancer (BLBC) remains a great challenge because of its
      clinically aggressive nature and lack of effective targeted therapy. We analyzed
      the potential anti-neoplastic effects of sanguinarine, a natural
      benzophenanthridine alkaloid, against BLBC cells. Sanguinarine treatment resulted
      in a reduction of cell migration, in a dose-dependent inhibition of cell
      viability and in the induction of cell death by apoptosis in both human (MDA-MB
      231 cells) and mouse (A17 cells) in vitro models of BLBC. In vivo experiments
      demonstrated that oral administration of sanguinarine reduced the development and
      growth of A17 transplantable tumors in FVB syngeneic mice. Western blotting
      analysis revealed that suppression of BLBC growth by sanguinarine was correlated
      with a concurrent upregulation of p27 and downregulation of cyclin D1 and with
      the inhibition of STAT3 activation. In addition, we identified sanguinarine as a
      potent inhibitor of dihydrofolate reductase (DHFR), able to impair enzyme
      activity even in methotrexate resistant MDA-MB-231 cells. These results provide
      evidence that sanguinarine is a promising anticancer drug for the treatment of
      BLBC.

PMID- 24875451
TI  - Shape-based virtual screening, docking, and molecular dynamics simulations to
      identify Mtb-ASADH inhibitors.
AB  - Aspartate beta-semialdehyde dehydrogenase (ASADH) is a key enzyme for the
      biosynthesis of essential amino acids and several important metabolites in
      microbes. Inhibition of ASADH enzyme is a promising drug target strategy against
      Mycobacterium tuberculosis (Mtb). In this work, in silico approach was used to
      identify potent inhibitors of Mtb-ASADH. Aspartyl beta-difluorophosphonate (beta
      AFP), a known lead compound, was used to understand the molecular recognition
      interactions (using molecular docking and molecular dynamics analysis). This
      analysis helped in validating the computational protocol and established the
      participation of Arg99, Glu224, Cys130, Arg249, and His256 amino acids as the key
      amino acids in stabilizing ligand-enzyme interactions for effective binding, an
      essential feature is H-bonding interactions with the two arginyl residues at the
      two ends of the ligand. Best binding conformation of beta-AFP was selected as a
      template for shape-based virtual screening (ZINC and NCI databases) to identify
      compounds that competitively inhibit the Mtb-ASADH. The top rank hits were
      further subjected to ADME and toxicity filters. Final filter was based on
      molecular docking analysis. Each screened molecule carries the characteristics of
      the highly electronegative groups on both sides separated by an average distance
      of 6 A. Finally, the best predicted 20 compounds exhibited minimum three H
      bonding interactions with Arg99 and Arg249. These identified hits can be further
      used for designing the more potent inhibitors against ASADH family. MD
      simulations were also performed on two selected compounds (NSC4862 and
      ZINC02534243) for further validation. During the MD simulations, both compounds
      showed same H-bonding interactions and remained bound to key active residues of
      Mtb-ASADH. 

PMID- 24875449
TI  - Class A scavenger receptor deficiency augments angiotensin II-induced vascular
      remodeling.
AB  - Class A scavenger receptor (SR-A) is a multifunctional molecule that participates
      in macrophage-mediated inflammation. Here we evaluated the role of SR-A in
      angiotensin II (Ang II)-induced hypertensive vascular remodeling. Chronic
      infusion of Ang II leads to an increased systolic blood pressure both in SR-A
      knockout (SR-A(-/-)) and wild type (SR-A(+/+)) mice with no significant
      difference between these two groups. SR-A(-/-) hypertensive mice, however,
      exhibited a marked augmentation of arterial wall thickening and vascular cell
      proliferation compared with SR-A(+/+) hypertensive mice. M1 macrophage markers
      were increased whereas M2 macrophage markers were decreased in vascular tissues
      of SR-A(-/-) mice. Co-culture experiments revealed that more pro-inflammatory
      cytokines like TNF-alpha were produced by SR-A(-/-) peritoneal macrophages
      leading to a stronger proliferation of primary vascular smooth muscle cells in
      vitro. In addition, SR-A(-/-) macrophages were more prone to lipopolysaccharide
      induced M1 differentiation while resisting interleukin-4-induced M2
      differentiation. Importantly, transplantation of SR-A(-/-) bone marrow into SR
      A(+/+) mice significantly augmented Ang II-induced vascular remodeling. These
      results show that SR-A is critical for Ang II-induced vascular remodeling by
      regulating macrophage polarization. Therefore, SR-A may be a useful therapeutic
      target for the intervention of hypertensive vascular remodeling.

PMID- 24875454
TI  - A study of allosteric binding behaviour of a 1,3-alternate thiacalix[4]arene
      based receptor using fluorescence signal.
AB  - A novel heteroditopic thiacalix[4]arene receptor L possessing 1,3-alternate
      conformation, which contains two pyrene moieties attached to the lower rim via
      urea linkages together with a crown ether moiety appended at the opposite side of
      the thiacalix[4]arene cavity, has been synthesized. The complexation behaviour of
      receptor L was studied by means of fluorescence spectra and (1)H NMR titration
      experiments in the presence of K(+) ions and a variety of other anions. The
      results suggested that receptor L can complex efficiently via the urea cavity or
      the crown ether moiety, and a positive/negative allosteric effect operating in
      receptor L was observed.

PMID- 24875452
TI  - Heat-shock protein 70 modulates apoptosis signal-regulating kinase 1 in stressed
      hepatocytes of Mugil cephalus.
AB  - Oxidative stress causes damage at the cellular level and activates a number of
      signaling pathways. Heat-shock proteins (HSPs) play an important role in repair
      and protective mechanisms under cell response to stress conditions. HSP70 has
      been shown to act as an inhibitor of apoptosis. Apoptosis signal-regulating
      kinase-1 (ASK1) activity is regulated at multiple levels, one of which is through
      inhibition by cytosolic chaperons HSP70. The current study was aimed to
      investigate the alteration in signaling molecules that allow the fish to survive
      under stressed natural field conditions. The study also investigates the
      variation in biomolecular composition of hepatocytes by using Fourier transform
      infrared spectroscopy. The impact of stress on hepatocytes was assessed by
      measuring the level of lipid peroxides (LPO), catalase activity (CAT) and
      assessing the changes in hepatocytes of Mugil cephalus inhabiting Kovalam and
      Ennore estuaries. The expression of HSP70 and ASK1 were analyzed by immunoblot
      analysis and ELISA, respectively. The spectral analysis showed variations in
      biomolecular composition of hepatocytes at a wave number region of 4,000-400 cm(
      1). There was significant decrease of CAT activity (p < 0.01) (25 %) with
      significant increase of LPO (p < 0.001) (35 %) and HSP70 (p < 0.001) and
      insignificant increase of ASK1 (p < 0.05) (16 %) in fish hepatocytes inhabiting
      Ennore estuary than Kovalam estuary. In conclusion, the present study suggests
      that the survival of fish in the Ennore estuary under stressed condition may be
      due to the upregulation of HSP70 that mediates the altered signal pathway which
      promotes cellular resistance against apoptosis.

PMID- 24875453
TI  - Beyond screening for risk factors: objective detection of strabismus and
      amblyopia.
AB  - IMPORTANCE: Commercially available automated vision screening devices assess
      refractive risk factors, not amblyopia or strabismus, underreferring affected
      children and overreferring healthy children. Nearly half of affected children are
      not identified until after age 5 years, when treatment is less effective.
      OBJECTIVES: To determine the diagnostic accuracy of the Pediatric Vision Scanner
      (PVS), a binocular retinal birefringence scanner, to objectively identify
      strabismus and amblyopia, and to compare retinal birefringence screening with a
      widely used automated pediatric screening device. DESIGN, SETTING, AND
      PARTICIPANTS: Three hundred consecutive preschool children (aged 2-6 years) were
      screened using the PVS and the SureSight Autorefractor at 2 pediatric
      ophthalmology private practices. A masked comprehensive pediatric ophthalmic
      examination provided the gold standard for determining sensitivity and
      specificity for each screening device. MAIN OUTCOMES AND MEASURES: The primary
      outcome was sensitivity and specificity of the PVS for detecting the targeted
      conditions, strabismus and amblyopia, in children aged 2 to 6 years. Secondary
      outcomes included the positive and negative likelihood ratios of the PVS for
      identifying the targeted conditions. In addition, sensitivity, specificity, and
      positive and negative likelihood ratios of the SureSight Autorefractor for the
      targeted conditions were assessed in the same cohort of children. RESULTS: Of the
      300 patients, 188 had strabismus only, amblyopia only, or both, and 112 had no
      strabismus or amblyopia. The sensitivity of the PVS to detect strabismus and
      amblyopia (0.97; 95% CI, 0.94-1.00) was significantly higher than that of the
      SureSight Autorefractor (0.74; 95% CI, 0.66-0.83). Specificity of the PVS for
      strabismus and amblyopia (0.87; 95% CI, 0.80-0.95) was significantly higher than
      that of the SureSight Autorefractor (0.62; 95% CI, 0.50-0.73). CONCLUSIONS AND
      RELEVANCE: The PVS identified children with strabismus and/or amblyopia with high
      sensitivity, outperforming the SureSight Autorefractor. Accurate, early detection
      of these conditions could improve long-term vision outcomes of affected preschool
      children.

PMID- 24875455
TI  - Diagnosis and management of nocardiosis after bone marrow stem cell
      transplantation in adults: lack of lymphocyte recovery as a major contributing
      factor.
AB  - Hematopoietic cell transplantation (HCT) is a curative treatment for
      hematological malignancies. This therapeutic approach is associated with a
      profound immune deficiency and an increased rate of opportunistic infections.
      Nocardiosis is a rare bacterial infection occurring mainly in patients with
      deficient cell-mediated immunity, such as AIDS patients or transplant recipients.
      Diagnosis of nocardiosis can be challenging, as signs and symptoms are non
      specific. Routine prophylaxis with trimethoprin/sulfamethoxazole (TMP/SMZ) does
      not prevent the risk of infection. Between May 2001 and December 2009, five cases
      of nocardiosis were diagnosed from the 366 allogeneic HCT recipients in our
      centre. Four patients developed a disseminated nocardiosis within the first year
      after HCT. The fifth patient presented a localized cutaneous nocardiosis. In
      disseminated cases, median total CD4+ T-cells were below 100 cells/MUL. Naive
      CD4+ CD45RA+/RO- T-cells were almost undetectable. CD8(+) T-cells and NK cells
      were below the normal range and CD19+ B-cell reconstitution was completely
      deficient. In a localized case, we observed a lack of naive thymic emigrants CD4+
      CD45RA+/RO- T-cells.

PMID- 24875457
TI  - The reduction of nosocomial MRSA infection in Germany: an analysis of data from
      the Hospital Infection Surveillance System (KISS) between 2007 and 2012.
AB  - BACKGROUND: Infections with multiresistant Gram negative pathogens are rising
      around the world, but many European countries have recently seen a decline in
      infections due to methicillin resistant Staphylococcus aureus (MRSA). We
      determined the percentage of nosocomial Staphylococcus aureus infections in
      Germany that were accounted for by MRSA in the past six years and looked for
      regional differences in the overall downward trend. METHODS: Data from the German
      Hospital Infection Surveillance System (Krankenhaus-Infektions-Surveillance
      System, KISS) from the years 2007-2012 were analyzed. In intensive care units,
      data on the following nosocomial infections were registered: primary sepsis,
      lower respiratory tract infections, and urinary tract infections; in surgical
      wards, data on postoperative wound infections were collected. RESULTS: The number
      of participating intensive care units varied from 465 to 645, while the number of
      participating surgical wards varied from 432 to 681. Over the period 2007-2012,
      the percentage of nosocomial Staphylococcus aureus infections that were due to
      MRSA dropped significantly, from 33% to 27%. More specifically, the percentage of
      infections due to MRSA dropped from 36% to 31% for primary sepsis and from 36% to
      30% for lower respiratory tract infections. Regression analysis revealed
      significantly lower MRSA fractions in the German states of Brandenburg (odds
      ratio [OR] 0.41), Bavaria (OR 0.73), and Saxony-Anhalt (OR 0.53), with higher
      fractions in Berlin (OR 1.59), Mecklenburg-West Pomerania (OR 1.91), Lower Saxony
      (OR 1.85), and North Rhine-Westphalia (OR 1.55). There were no significant
      differences in the remaining German states. CONCLUSION: In Germany, the
      percentage of nosocomial Staphylococcus aureus infections due to MRSA dropped
      significantly over the period 2007-2012. The causes of this decline are unclear;
      it may have resulted from human intervention, pathogen biology, or both.

PMID- 24875456
TI  - The role of patient-clinician information engagement and information seeking from
      nonmedical channels in fruit and vegetable intake among cancer patients.
AB  - Previous research suggests positive effects of health information seeking on
      prevention behaviors such as diet, exercise, and fruit and vegetable consumption.
      The present study builds upon this research and strengthens causal claims from it
      by examining the lagged effect of patient-clinician information engagement on
      fruit and vegetable consumption as well as the indirect effect on the outcome
      through seeking information from nonmedical channels. The results are based on
      data collected from a randomly drawn sample of breast, prostate, and colorectal
      cancer patients from the Pennsylvania Cancer Registry who completed mail surveys
      in the Fall of 2006 and 2007. There was a 65% response rate for baseline subjects
      (resulting n = 2,013); of those, 1,293 were interviewed 1 year later, and 1,257
      were available for our analyses. Results show a positive lagged main effect of
      patient-clinician information engagement at baseline on fruit and vegetable
      consumption at follow-up (B = 0.26, SE = 0.10, p = .01). The mediation analysis
      shows that patient-clinician information engagement leads to increased fruit and
      vegetable consumption among cancer patients, in part through patients'
      information seeking from nonmedical channels. Implications of these findings for
      the cancer patient population and for physicians are discussed.

PMID- 24875458
TI  - Birth weight and special educational needs: results of a population-based study
      in Berlin.
AB  - BACKGROUND: Preterm infants are at higher risk for developmental problems. The
      aim of this study is to quantify the relation between birth weight and special
      educational needs. METHODS: We analyzed data from the pre-school examinations of
      134 313 children in Berlin aged 5 to 6 who were examined between 2007 and 2011.
      RESULTS: Special educational needs were diagnosed in 8058 children (6.0%), 4943
      (61%) of whom had weighed 3000 g or more at birth. The percentage of children
      with special educational needs rose steadily with decreasing birth weight (2250
      2499 g, 9.2%; 1250-1499 g, 21.1%; less than 750 g, 35.6%). Logistic regression
      analysis yielded odds ratios and 99% confidence intervals for special educational
      needs that ranged from 1.32 [1.17-1.47] for birth weight 2750-2999 g to 12.83
      [7.48-22.03] for birth weight less than 750 g. Further risk factors were male sex
      (1.88 [1.75-2.03]), low social status (5.96 [5.21-6.82]), an immigrant background
      associated with poor German language skills in the family (1.63 [1.43-1.86]), and
      being raised by a single parent (1.21 [1.12-1.31]). On the other hand, nursery
      school and/or kindergarten enrollment for at least two years before entering
      school (0.82 [0.73-0.91]) and an immigrant background with good German skills in
      the family (0.39 [0.34-0.45]) were associated with lower rates of special
      educational needs. CONCLUSION: The risk of special educational needs increases
      already with moderately decreased birth weight. The most important factor other
      than birth weight is the family's social status. Although children of very low
      birth weight have a much higher rate of special educational needs than other
      children, they still make up only a small percentage of all children with special
      educational needs.

PMID- 24875460
TI  - Diminished sub-maximal quadriceps force control in anterior cruciate ligament
      reconstructed patients is related to quadriceps and hamstring muscle dyskinesia.
AB  - The aim of this study was to determine the effects of anterior cruciate ligament
      reconstruction (ACLR) on sub-maximal quadriceps force control with respect to
      quadriceps and hamstring muscle activity. Thirty ACLR individuals together with
      30 healthy individuals participated. With real-time visual feedback of muscle
      force output and electromyographic electrodes attached to the quadriceps and
      hamstring muscles, subjects performed an isometric knee extension task where they
      increased and decreased their muscle force output at 0.128Hz within a range of 5
      30% maximum voluntary capacity. The ACLR group completed the task with more error
      and increased medial hamstring and vastus medialis activation (p<0.05). Moderate
      negative correlations (p<0.05) were observed between quadriceps force control and
      medial (Spearman's rho=-0.448, p=0.022) and lateral (Spearman's rho=-0.401,
      p=0.034) hamstring activation in the ACLR group. Diminished quadriceps sub
      maximal force control in ACLR subjects was reflective of medial quadriceps and
      hamstring dyskinesia (i.e., altered muscle activity patterns and coordination
      deficits). Within the ACLR group however, augmented hamstring co-activation was
      associated with better quadriceps force control. Future studies should explore
      the convergent validity of quadriceps force control in ACLR patients. 

PMID- 24875459
TI  - Acquired hemophilia with inhibitors presenting as an emergency: misinterpretation
      of clotting results during direct oral anticoagulation.
AB  - BACKGROUND: Direct oral anticoagulants (DOACs) were recently introduced and are
      being increasingly prescribed. Most DOACs alter the values of traditional
      coagulation tests, such as the international normalized ratio (INR) or the
      activated partial thromboplastin time (aPTT). Although vitamin K antagonists
      raise the INR value to an extent that mirrors their anticoagulant effect, DOACs
      do not, in general, alter standard clotting values in any consistent way. Thus,
      there is a risk that abnormal INR and aPTT values can be misinterpreted. CASE
      ILLUSTRATION: A woman taking rivaroxaban, a DOAC, presented with ileus and was
      scheduled for urgent surgery. A prolonged aPTT was, at first, wrongly attributed
      to rivaroxaban, delaying the correct diagnosis of autoantibody-associated
      acquired hemophilia (a rare condition with incidence, 1.34-1.48 cases per million
      people per year). The patient had a history of unusually intense bleeding in the
      skin and mucous membranes during anticoagulant treatment. Her aPTT had been
      prolonged even before any anticoagulants were taken. COURSE: The operation was
      delayed to await the elimination of rivaroxaban. The aPTT was still prolonged 24
      hours later. The diagnosis of autoantibody-associated acquired hemophilia was
      suspected and then confirmed by the measurement of a factor VIII residual
      activity of 1% and the demonstration of factor VIII inhibition at an intensity of
      9.2 Bethesda units per mL. CONCLUSION: The causes of abnormal clotting test
      results must be clarified before beginning anticoagulant therapy. Unusually
      intense bleeding during oral anticoagulation should arouse suspicion of a
      previously undiagnosed acquired coagulopathy, e.g., antibody-associated acquired
      hemophilia.

PMID- 24875461
TI  - Associations between cervical and scapular posture and the spatial distribution
      of trapezius muscle activity.
AB  - The first aim of this investigation was to quantify the distribution of trapezius
      muscle activity with different scapular postures while seated. The second aim of
      this investigation was to examine the association between changes in cervical and
      scapular posture when attempting to recruit different subdivisions of the
      trapezius muscle. Cervical posture, scapular posture, and trapezius muscle
      activity were recorded from 20 healthy participants during three directed
      shoulder postures. Planar angles formed by reflective markers placed on the
      acromion process, C7, and tragus were used to quantify cervical and scapular
      posture. Distribution of trapezius muscle activity was recorded using two high
      density surface electromyography (HDsEMG) electrodes positioned over the upper,
      middle, and lower trapezius. Results validated the assumption that directed
      scapular postures preferentially activate different subdivisions of the trapezius
      muscle. In particular, scapular depression was associated with a more inferior
      location of trapezius muscle activity (r=0.53). Scapular elevation was coupled
      with scapular abduction (r=0.52). Scapular adduction was coupled with cervical
      extension (r=0.35); all other changes in cervical posture were independent of
      changes in scapular posture. This investigation provides empirical support for
      reductions in static loading of the upper trapezius and improvements in neck
      posture through verbal cueing of scapular posture. 

PMID- 24875462
TI  - Fuzzy MUAP recognition in HSR-EMG detection basing on morphological features.
AB  - The idea of 'besides the MU properties and depending on the recording techniques,
      MUAPs can have unique pattern' was adopted. The aim of this work was to recognise
      whether a Laplacian-detected MUAP is isolated or overlapped basing on novel
      morphological features using fuzzy classifier. Training data set was constructed
      to elaborate and test the 'if-then' fuzzy rules using signals provided by three
      muscles: the abductor pollicis brevis (APB), the first dorsal interosseous (FDI)
      and the biceps brachii (BB) muscles of 11 healthy subjects. The proposed fuzzy
      classier recognized automatically the isolated MUAPs with a performance of 95.03%
      which was improved to 97.8% by adjusting the certainty grades of rules using
      genetic algorithms (GA). Synthetic signals were used as reference to further
      evaluate the performance of the elaborated classifier. The recognition of the
      isolated MUAPs depends largely on noise level and is acceptable down to the
      signal to noise ratio of 20 dB with a detection probability of 0.96. The
      recognition of overlapped MUAPs depends slightly on the noise level with a
      detection probability of about 0.8. The corresponding misrecognition is caused
      principally by the synchronisation and the small overlapping degree. 

PMID- 24875463
TI  - Absorption, distribution, metabolism, and excretion of the novel antibacterial
      prodrug tedizolid phosphate.
AB  - Tedizolid phosphate is a novel antibacterial prodrug with potent activity against
      Gram-positive pathogens. In vitro and in vivo studies demonstrated that the
      prodrug is rapidly converted by nonspecific phosphatases to the biologically
      active moiety tedizolid. Single oral dose radiolabeled (14)C-tedizolid phosphate
      kinetic studies in human subjects (100 uCi in 204 mg tedizolid phosphate free
      acid) confirmed a rapid time to maximum tedizolid concentration (Tmax, 1.28
      hours), a long terminal half-life (10.6 hours), and a Cmax of 1.99 ug/ml.
      Metabolite analysis of plasma, fecal, and urine samples from rats, dogs, and
      humans confirmed that tedizolid is the only measurable metabolite in plasma after
      intravenous (in animals only) or oral administration and that tedizolid sulfate
      is the major metabolite excreted from the body. Excellent mass balance recovery
      was achieved and demonstrated that fecal excretion is the predominant (80-90%)
      route of elimination across species, primarily as tedizolid sulfate. Urine
      excretion accounted for the balance of drug elimination but contained a broader
      range of minor metabolites. Glucuronidation products were not detected. Similar
      results were observed in rats and dogs after both intravenous and oral
      administration. The tedizolid metabolites showed less potent antibacterial
      activity than tedizolid. The observations from these studies support once daily
      dosing of tedizolid phosphate and highlight important metabolism and excretion
      features that differentiate tedizolid phosphate from linezolid. 

PMID- 24875465
TI  - Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF)
      predictors of police officer problem behavior.
AB  - The purpose of this study was to investigate the predictive validity of the
      Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF) in a
      sample of law enforcement officers. MMPI-2-RF scores were collected from
      preemployment psychological evaluations of 136 male police officers, and
      supervisor ratings of performance and problem behavior were subsequently obtained
      during the initial probationary period. The sample produced meaningfully lower
      and less variant substantive scale scores than the general population and the
      MMPI-2-RF Police Candidate comparison group, which significantly affected effect
      sizes for the zero-order correlations. After applying a correction for range
      restriction, MMPI-2-RF substantive scales demonstrated moderate to strong
      associations with criteria, particularly in the Emotional Dysfunction and
      Interpersonal Functioning domains. Relative risk ratio analyses showed that
      cutoffs of 45T and 50T maintained reasonable selection ratios because of the
      exceptionally low scores in this sample and were associated with significantly
      increased risk for problematic behavior. These results provide support for the
      predictive validity of the MMPI-2-RF substantive scales in this setting.
      Implications of these findings and limitations of these results are discussed. 

PMID- 24875464
TI  - Factors influencing the CNS distribution of a novel MEK-1/2 inhibitor:
      implications for combination therapy for melanoma brain metastases.
AB  - Brain metastases are a major cause of mortality in patients with advanced
      melanoma. Adequate brain distribution of targeted agents for melanoma will be
      critical for treatment success. Recently, improvement in overall survival led to
      US Food and Drug Administration (FDA) approval of the v-raf murine sarcoma viral
      oncogene homolog B (BRAF) inhibitors, vemurafenib and dabrafenib, and the mitogen
      activated protein kinase kinase-1 (MEK)-1/2 inhibitor, trametinib. However, brain
      metastases and emergence of resistance remain a significant problem. MEK-1/2 is
      downstream of BRAF in the mitogen-activated protein kinase (MAPK) signaling
      pathway, making it an attractive target to combat resistance. The recently
      approved combination of dabrafenib and trametinib has shown improvement in
      progression-free survival; however, adequate brain distribution of both compounds
      is required to effectively treat brain metastases. In previous studies, we found
      limited brain distribution of dabrafenib. The purpose of the current study was to
      investigate factors influencing the brain distribution of trametinib. In vitro
      studies indicated that trametinib is a substrate for both P-glycoprotein (P-gp)
      and Bcrp, efflux transporters found at the blood-brain barrier. In vivo studies
      in transgenic mouse models confirmed that P-gp plays an important role in
      restricting brain distribution of trametinib. The brain-to-plasma partition
      coefficient (AUCbrain/AUCplasma) was approximately 5-fold higher in Mdr1a/b((-/
      )) (P-gp knockout) and Mdr1a/b((-/-))Bcrp1((-/-)) (triple knockout) mice when
      compared with wild-type and Bcrp1((-/-)) (Bcrp knockout) mice. The brain
      distribution of trametinib was similar between the wild-type and Bcrp knockout
      mice. These results show that P-gp plays an important role in limiting brain
      distribution of trametinib and may have important implications for use of
      trametinib as single agent or in combination therapy for treatment of melanoma
      brain metastases. 

PMID- 24875466
TI  - Early initiation of oral feeding following upper gastrointestinal tumor surgery:
      a randomized controlled trial.
AB  - OBJECTIVES: Despite increasing trends toward the early initiation of oral feeding
      after gastrointestinal (GI) surgeries, current evidence has not been convincing.
      The present randomized clinical trial aimed to compare the clinical outcomes of
      early oral feeding (EOF) with late oral feeding (LOF) following surgery for upper
      GI tumors. METHODS: One hundred and nine consecutive patients with esophageal or
      gastric tumors undergoing surgical resection in two hospitals in Tehran, Iran,
      were enrolled in this prospective randomized controlled trial, and were randomly
      assigned to a group starting EOF on the first postoperative day and another group
      that remained nil by mouth until the return of bowel sounds (LOF group). The
      clinical and surgical outcomes were compared between the two groups. RESULTS: The
      clinical outcomes were significantly better in the patients in the EOF group (p <
      0.05). Repeated nil per os (14.8 vs. 30.9 %) and re-hospitalization (1.8 vs. 7.3
      %) were more common in LOF group (p < 0.0001). Additionally, gas passage,
      nasogastric tube (NGT) discharge, a decrease in intravenous serum to less than
      1000 ml per day, the time to start a soft diet and hospital discharge following
      surgery occurred significantly earlier in the EOF group than in the LOF group (p
      < 0.0001). CONCLUSION: Early oral feeding after the surgical resection of
      esophageal and gastric tumors is safe, and is associated with favorable early in
      hospital outcomes and a sooner return to physiological GI function and hospital
      discharge.

PMID- 24875467
TI  - Successful laparoscopic gastric resection and safe introduction of a single
      incision technique for gastric submucosal tumors located near the esophagogastric
      junction.
AB  - PURPOSE: Laparoscopic gastric resection cannot be easily applied for submucosal
      tumors near the esophagogastric junction (NEJ-SMTs). Furthermore, there have been
      no reports of single-incision laparoscopic surgery (SILS) for NEJ-SMTs. We
      evaluated our laparoscopic surgical outcomes for NEJ-SMTs, including a newly
      introduced phase of SILS. METHODS: We retrospectively reviewed a total of 18
      patients diagnosed with NEJ-SMTs who underwent laparoscopic surgery between April
      2002 and September 2013. RESULTS: All patients underwent laparoscopic gastric
      resection without local complications and with a negative surgical margin,
      including 12 patients treated with conventional laparoscopic surgery (CLS) and
      six patients treated with SILS. The mean length of the operation was 184.3 +/-
      52.3 min, and the mean blood loss was 19.2 +/- 17.7 mL. All patients underwent
      complete resection. There were no statistically significant differences between
      the CLS and SILS groups in terms of the surgical outcomes. CONCLUSION: Despite
      this challenging location of the tumor, laparoscopic gastric resection for NEJ
      SMTs is safe and feasible. Furthermore, SILS can provide a better cosmetic
      result, which can lead to better global patient satisfaction in carefully
      selected patients with NEJ-SMTs.

PMID- 24875468
TI  - Investigating language lateralization during phonological and semantic fluency
      tasks using functional transcranial Doppler sonography.
AB  - Although there is consensus that the left hemisphere plays a critical role in
      language processing, some questions remain. Here we examine the influence of
      overt versus covert speech production on lateralization, the relationship between
      lateralization and behavioural measures of language performance and the strength
      of lateralization across the subcomponents of language. The present study used
      functional transcranial Doppler sonography (fTCD) to investigate lateralization
      of phonological and semantic fluency during both overt and covert word generation
      in right-handed adults. The laterality index (LI) was left lateralized in all
      conditions, and there was no difference in the strength of LI between overt and
      covert speech. This supports the validity of using overt speech in fTCD studies,
      another benefit of which is a reliable measure of speech production. 

PMID- 24875469
TI  - Arthroscopic Hip Revision Surgery for Residual Femoroacetabular Impingement
      (FAI): Surgical Outcomes Compared With a Matched Cohort After Primary
      Arthroscopic FAI Correction.
AB  - BACKGROUND: There are limited data reporting outcomes after revision arthroscopic
      surgery for residual femoroacetabular impingement (FAI). HYPOTHESIS: (1) Revision
      arthroscopic FAI correction results in improved outcomes, but they are inferior
      to those of primary arthroscopic FAI correction. (2) Improved postrevision
      radiographic parameters are predictive of better outcomes. STUDY DESIGN: Cohort
      study; Level of evidence, 3. METHODS: Patients who underwent arthroscopic hip
      revision for residual FAI were reviewed. Pathomorphological findings,
      intraoperative findings, and preoperative and postoperative modified Harris Hip
      Score (MHHS), Short Form-12 (SF-12), and pain on a visual analog scale (VAS)
      values were evaluated. Outcomes after revision arthroscopic FAI correction were
      compared with outcomes of a matched cohort who underwent primary arthroscopic FAI
      correction. RESULTS: A total of 79 patients (85 hips) with a mean age of 29.5
      years underwent arthroscopic revision FAI correction (mean follow-up, 26 months).
      The labrum was debrided (27 hips), repaired (49 hips), or reconstructed (7 hips).
      Two labrums were stable and required no treatment. The results of revision
      arthroscopic FAI correction were compared with those of 220 age- and sex-matched
      patients (237 hips) who underwent primary arthroscopic FAI correction (mean
      follow-up, 23 months). The mean improvement in outcome scores after revision FAI
      correction was 17.8 (MHHS), 12.5 (SF-12), and 1.4 (VAS) points compared with 23.4
      (MHHS), 19.7 (SF-12), and 4.6 (VAS) points after primary arthroscopic FAI
      correction. The mean improvement was significantly better in the primary cohort
      compared with the revision cohort (P < .01 for MHHS, SF-12, and VAS values).
      Good/excellent results were achieved in 81.7% of the primary cohort and 62.7% of
      the revision cohort (P < .01). Greater postoperative head-neck offset (P = .024),
      subspine/anterior inferior iliac spine (AIIS) decompression (P = .014), labral
      repair/reconstruction (P = .009), and capsular plication (P = .032) were
      significant predictors for better outcomes after revision surgery. CONCLUSION:
      Arthroscopic hip revision surgery for residual FAI yielded significantly improved
      outcome measures, but these were inferior to those after primary arthroscopic FAI
      corrective surgery. Improved femoral head-neck offset after cam decompression,
      identification and treatment of subspine/AIIS impingement, labral
      preservation/reconstruction, and capsular preservation/plication may be paramount
      to achieve satisfactory outcomes.

PMID- 24875470
TI  - Physics and financial economics (1776-2014): puzzles, Ising and agent-based
      models.
AB  - This short review presents a selected history of the mutual fertilization between
      physics and economics--from Isaac Newton and Adam Smith to the present. The
      fundamentally different perspectives embraced in theories developed in financial
      economics compared with physics are dissected with the examples of the volatility
      smile and of the excess volatility puzzle. The role of the Ising model of phase
      transitions to model social and financial systems is reviewed, with the concepts
      of random utilities and the logit model as the analog of the Boltzmann factor in
      statistical physics. Recent extensions in terms of quantum decision theory are
      also covered. A wealth of models are discussed briefly that build on the Ising
      model and generalize it to account for the many stylized facts of financial
      markets. A summary of the relevance of the Ising model and its extensions is
      provided to account for financial bubbles and crashes. The review would be
      incomplete if it did not cover the dynamical field of agent-based models (ABMs),
      also known as computational economic models, of which the Ising-type models are
      just special ABM implementations. We formulate the 'Emerging Intelligence Market
      Hypothesis' to reconcile the pervasive presence of 'noise traders' with the near
      efficiency of financial markets. Finally, we note that evolutionary biology, more
      than physics, is now playing a growing role to inspire models of financial
      markets.

PMID- 24875471
TI  - PTHGRN: unraveling post-translational hierarchical gene regulatory networks using
      PPI, ChIP-seq and gene expression data.
AB  - Interactions among transcriptional factors (TFs), cofactors and other proteins or
      enzymes can affect transcriptional regulatory capabilities of eukaryotic
      organisms. Post-translational modifications (PTMs) cooperate with TFs and
      epigenetic alterations to constitute a hierarchical complexity in transcriptional
      gene regulation. While clearly implicated in biological processes, our
      understanding of these complex regulatory mechanisms is still limited and
      incomplete. Various online software have been proposed for uncovering
      transcriptional and epigenetic regulatory networks, however, there is a lack of
      effective web-based software capable of constructing underlying interactive
      organizations between post-translational and transcriptional regulatory
      components. Here, we present an open web server, post-translational hierarchical
      gene regulatory network (PTHGRN) to unravel relationships among PTMs, TFs,
      epigenetic modifications and gene expression. PTHGRN utilizes a graphical
      Gaussian model with partial least squares regression-based methodology, and is
      able to integrate protein-protein interactions, ChIP-seq and gene expression data
      and to capture essential regulation features behind high-throughput data. The
      server provides an integrative platform for users to analyze ready-to-use public
      high-throughput Omics resources or upload their own data for systems biology
      study. Users can choose various parameters in the method, build network
      topologies of interests and dissect their associations with biological functions.
      Application of the software to stem cell and breast cancer demonstrates that it
      is an effective tool for understanding regulatory mechanisms in biological
      complex systems. PTHGRN web server is publically available at web site
      http://www.byanbioinfo.org/pthgrn. 

PMID- 24875472
TI  - SPIB and BATF provide alternate determinants of IRF4 occupancy in diffuse large B
      cell lymphoma linked to disease heterogeneity.
AB  - Interferon regulatory factor 4 (IRF4) is central to the transcriptional network
      of activated B-cell-like diffuse large B-cell lymphoma (ABC-DLBCL), an aggressive
      lymphoma subgroup defined by gene expression profiling. Since cofactor
      association modifies transcriptional regulatory input by IRF4, we assessed genome
      occupancy by IRF4 and endogenous cofactors in ABC-DLBCL cell lines. IRF4 partners
      with SPIB, PU.1 and BATF genome-wide, but SPIB provides the dominant IRF4 partner
      in this context. Upon SPIB knockdown IRF4 occupancy is depleted and neither PU.1
      nor BATF acutely compensates. Integration with ENCODE data from lymphoblastoid
      cell line GM12878, demonstrates that IRF4 adopts either SPIB- or BATF-centric
      genome-wide distributions in related states of post-germinal centre B-cell
      transformation. In primary DLBCL high-SPIB and low-BATF or the reciprocal low
      SPIB and high-BATF mRNA expression links to differential gene expression profiles
      across nine data sets, identifying distinct associations with SPIB occupancy,
      signatures of B-cell differentiation stage and potential pathogenetic mechanisms.
      In a population-based patient cohort, SPIBhigh/BATFlow-ABC-DLBCL is enriched for
      mutation of MYD88, and SPIBhigh/BATFlow-ABC-DLBCL with MYD88-L265P mutation
      identifies a small subgroup of patients among this otherwise aggressive disease
      subgroup with distinct favourable outcome. We conclude that differential
      expression of IRF4 cofactors SPIB and BATF identifies biologically and clinically
      significant heterogeneity among ABC-DLBCL.

PMID- 24875473
TI  - Lessons from miR-143/145: the importance of cell-type localization of miRNAs.
AB  - miR-143 and miR-145 are co-expressed microRNAs (miRNAs) that have been
      extensively studied as potential tumor suppressors. These miRNAs are highly
      expressed in the colon and are consistently reported as being downregulated in
      colorectal and other cancers. Through regulation of multiple targets, they elicit
      potent effects on cancer cell growth and tumorigenesis. Importantly, a recent
      discovery demonstrates that miR-143 and miR-145 are not expressed in colonic
      epithelial cells; rather, these two miRNAs are highly expressed in mesenchymal
      cells such as fibroblasts and smooth muscle cells. The expression patterns of miR
      143 and miR-145 and other miRNAs were initially determined from tissue level data
      without consideration that multiple different cell types, each with their own
      unique miRNA expression patterns, make up each tissue. Herein, we discuss the
      early reports on the identification of dysregulated miR-143 and miR-145
      expression in colorectal cancer and how lack of consideration of cellular
      composition of normal tissue led to the misconception that these miRNAs are
      downregulated in cancer. We evaluate mechanistic data from miR-143/145 studies in
      context of their cell type-restricted expression pattern and the potential of
      these miRNAs to be considered tumor suppressors. Further, we examine other
      examples of miRNAs being investigated in inappropriate cell types modulating
      pathways in a non-biological fashion. Our review highlights the importance of
      determining the cellular expression pattern of each miRNA, so that downstream
      studies are conducted in the appropriate cell type. 

PMID- 24875474
TI  - Genomic and proteomic analysis of transcription factor TFII-I reveals insight
      into the response to cellular stress.
AB  - The ubiquitously expressed transcription factor TFII-I exerts both positive and
      negative effects on transcription. Using biotinylation tagging technology and
      high-throughput sequencing, we determined sites of chromatin interactions for
      TFII-I in the human erythroleukemia cell line K562. This analysis revealed that
      TFII-I binds upstream of the transcription start site of expressed genes, both
      upstream and downstream of the transcription start site of repressed genes, and
      downstream of RNA polymerase II peaks at the ATF3 and other stress responsive
      genes. At the ATF3 gene, TFII-I binds immediately downstream of a Pol II peak
      located 5 kb upstream of exon 1. Induction of ATF3 expression increases
      transcription throughout the ATF3 gene locus which requires TFII-I and correlates
      with increased association of Pol II and Elongin A. Pull-down assays demonstrated
      that TFII-I interacts with Elongin A. Partial depletion of TFII-I expression
      caused a reduction in the association of Elongin A with and transcription of the
      DNMT1 and EFR3A genes without a decrease in Pol II recruitment. The data reveal
      different interaction patterns of TFII-I at active, repressed, or inducible
      genes, identify novel TFII-I interacting proteins, implicate TFII-I in the
      regulation of transcription elongation and provide insight into the role of TFII
      I during the response to cellular stress. 

PMID- 24875475
TI  - siPools: highly complex but accurately defined siRNA pools eliminate off-target
      effects.
AB  - Short interfering RNAs (siRNAs) are widely used as tool for gene inactivation in
      basic research and therapeutic applications. One of the major shortcomings of
      siRNA experiments are sequence-specific off-target effects. Such effects are
      largely unpredictable because siRNAs can affect partially complementary sequences
      and function like microRNAs (miRNAs), which inhibit gene expression on mRNA
      stability or translational levels. Here we demonstrate that novel, enzymatically
      generated siRNA pools-referred to as siPools-containing up to 60 accurately
      defined siRNAs eliminate off-target effects. This is achieved by the low
      concentration of each individual siRNA diluting sequence-specific off-target
      effects below detection limits. In fact, whole transcriptome analyses reveal that
      single siRNA transfections can severely affect global gene expression. However,
      when complex siRNA pools are transfected, almost no transcriptome alterations are
      observed. Taken together, we present enzymatically produced complex but
      accurately defined siRNA pools with potent on-target silencing but without
      detectable off-target effects. 

PMID- 24875476
TI  - DDI-CPI, a server that predicts drug-drug interactions through implementing the
      chemical-protein interactome.
AB  - Drug-drug interactions (DDIs) may cause serious side-effects that draw great
      attention from both academia and industry. Since some DDIs are mediated by
      unexpected drug-human protein interactions, it is reasonable to analyze the
      chemical-protein interactome (CPI) profiles of the drugs to predict their DDIs.
      Here we introduce the DDI-CPI server, which can make real-time DDI predictions
      based only on molecular structure. When the user submits a molecule, the server
      will dock user's molecule across 611 human proteins, generating a CPI profile
      that can be used as a feature vector for the pre-constructed prediction model. It
      can suggest potential DDIs between the user's molecule and our library of 2515
      drug molecules. In cross-validation and independent validation, the server
      achieved an AUC greater than 0.85. Additionally, by investigating the CPI
      profiles of predicted DDI, users can explore the PK/PD proteins that might be
      involved in a particular DDI. A 3D visualization of the drug-protein interaction
      will be provided as well. The DDI-CPI is freely accessible at http://cpi.bio
      x.cn/ddi/. 

PMID- 24875477
TI  - Cooperative gene regulation by microRNA pairs and their identification using a
      computational workflow.
AB  - MicroRNAs (miRNAs) are an integral part of gene regulation at the post
      transcriptional level. Recently, it has been shown that pairs of miRNAs can
      repress the translation of a target mRNA in a cooperative manner, which leads to
      an enhanced effectiveness and specificity in target repression. However, it
      remains unclear which miRNA pairs can synergize and which genes are target of
      cooperative miRNA regulation. In this paper, we present a computational workflow
      for the prediction and analysis of cooperating miRNAs and their mutual target
      genes, which we refer to as RNA triplexes. The workflow integrates methods of
      miRNA target prediction; triplex structure analysis; molecular dynamics
      simulations and mathematical modeling for a reliable prediction of functional RNA
      triplexes and target repression efficiency. In a case study we analyzed the human
      genome and identified several thousand targets of cooperative gene regulation.
      Our results suggest that miRNA cooperativity is a frequent mechanism for an
      enhanced target repression by pairs of miRNAs facilitating distinctive and fine
      tuned target gene expression patterns. Human RNA triplexes predicted and
      characterized in this study are organized in a web resource at www.sbi.uni
      rostock.de/triplexrna/. 

PMID- 24875478
TI  - Analysis of tetra- and hepta-nucleotides motifs promoting -1 ribosomal
      frameshifting in Escherichia coli.
AB  - Programmed ribosomal -1 frameshifting is a non-standard decoding process
      occurring when ribosomes encounter a signal embedded in the mRNA of certain
      eukaryotic and prokaryotic genes. This signal has a mandatory component, the
      frameshift motif: it is either a Z_ZZN tetramer or a X_XXZ_ZZN heptamer (where
      ZZZ and XXX are three identical nucleotides) allowing cognate or near-cognate
      repairing to the -1 frame of the A site or A and P sites tRNAs. Depending on the
      signal, the frameshifting frequency can vary over a wide range, from less than 1%
      to more than 50%. The present study combines experimental and bioinformatics
      approaches to carry out (i) a systematic analysis of the frameshift propensity of
      all possible motifs (16 Z_ZZN tetramers and 64 X_XXZ_ZZN heptamers) in
      Escherichia coli and (ii) the identification of genes potentially using this mode
      of expression amongst 36 Enterobacteriaceae genomes. While motif efficiency
      varies widely, a major distinctive rule of bacterial -1 frameshifting is that the
      most efficient motifs are those allowing cognate re-pairing of the A site tRNA
      from ZZN to ZZZ. The outcome of the genomic search is a set of 69 gene clusters,
      59 of which constitute new candidates for functional utilization of -1
      frameshifting. 

PMID- 24875479
TI  - BiQ Analyzer HiMod: an interactive software tool for high-throughput locus
      specific analysis of 5-methylcytosine and its oxidized derivatives.
AB  - Recent data suggest important biological roles for oxidative modifications of
      methylated cytosines, specifically hydroxymethylation, formylation and
      carboxylation. Several assays are now available for profiling these DNA
      modifications genome-wide as well as in targeted, locus-specific settings. Here
      we present BiQ Analyzer HiMod, a user-friendly software tool for sequence
      alignment, quality control and initial analysis of locus-specific DNA
      modification data. The software supports four different assay types, and it leads
      the user from raw sequence reads to DNA modification statistics and publication
      quality plots. BiQ Analyzer HiMod combines well-established graphical user
      interface of its predecessor tool, BiQ Analyzer HT, with new and extended
      analysis modes. BiQ Analyzer HiMod also includes updates of the analysis
      workspace, an intuitive interface, a custom vector graphics engine and support of
      additional input and output data formats. The tool is freely available as a stand
      alone installation package from http://biq-analyzer-himod.bioinf.mpi-inf.mpg.de/.

PMID- 24875480
TI  - The strength of the template effect attracting nucleotides to naked DNA.
AB  - The transmission of genetic information relies on Watson-Crick base pairing
      between nucleoside phosphates and template bases in template-primer complexes.
      Enzyme-free primer extension is the purest form of the transmission process,
      without any chaperon-like effect of polymerases. This simple form of copying of
      sequences is intimately linked to the origin of life and provides new
      opportunities for reading genetic information. Here, we report the dissociation
      constants for complexes between (deoxy)nucleotides and template-primer complexes,
      as determined by nuclear magnetic resonance and the inhibitory effect of
      unactivated nucleotides on enzyme-free primer extension. Depending on the
      sequence context, Kd's range from 280 mM for thymidine monophosphate binding to a
      terminal adenine of a hairpin to 2 mM for a deoxyguanosine monophosphate binding
      in the interior of a sequence with a neighboring strand. Combined with rate
      constants for the chemical step of extension and hydrolytic inactivation, our
      quantitative theory explains why some enzyme-free copying reactions are
      incomplete while others are not. For example, for GMP binding to ribonucleic
      acid, inhibition is a significant factor in low-yielding reactions, whereas for
      amino-terminal DNA hydrolysis of monomers is critical. Our results thus provide a
      quantitative basis for enzyme-free copying. 

PMID- 24875482
TI  - Non-aneurysmatic rupture of an iliac artery presenting as pseudoaneurysm followed
      by endovascular treatment.

PMID- 24875481
TI  - TET1 is a maintenance DNA demethylase that prevents methylation spreading in
      differentiated cells.
AB  - TET1 is a 5-methylcytosine dioxygenase and its DNA demethylating activity has
      been implicated in pluripotency and reprogramming. However, the precise role of
      TET1 in DNA methylation regulation outside of developmental reprogramming is
      still unclear. Here, we show that overexpression of the TET1 catalytic domain but
      not full length TET1 (TET1-FL) induces massive global DNA demethylation in
      differentiated cells. Genome-wide mapping reveals that 5-hydroxymethylcytosine
      production by TET1-FL is inhibited as DNA methylation increases, which can be
      explained by the preferential binding of TET1-FL to unmethylated CpG islands
      (CGIs) through its CXXC domain. TET1-FL specifically accumulates 5
      hydroxymethylcytosine at the edges of hypomethylated CGIs, while knockdown of
      endogenous TET1 induces methylation spreading from methylated edges into
      hypomethylated CGIs. We also found that gene expression changes after TET1-FL
      overexpression are relatively small and independent of its dioxygenase function.
      Thus, our results identify TET1 as a maintenance DNA demethylase that does not
      purposely decrease methylation levels, but specifically prevents aberrant
      methylation spreading into CGIs in differentiated cells. 

PMID- 24875485
TI  - Association between pesticide exposure and suicide rates in Brazil.
AB  - INTRODUCTION: The association between pesticide use and an increased suicide risk
      is a controversial issue. Previous studies have shown higher rates of suicide
      among agricultural workers and people living in small municipalities, but have
      not identified the causes of these results. OBJECTIVE: To investigate the
      association between pesticide exposure and suicide rates. METHODS: Crude suicide
      rates of a 15-year time series (1996-2010) were examined, followed by an
      ecological study using age-standardized suicide rates for the period 2006-2010.
      The unit of analysis was all 558 Brazilian micro-regions. Pesticide exposure was
      evaluated according to the proportion of farms that used pesticides and had
      reported cases of pesticide poisonings. The statistics were analysed using
      Pearson's correlation and multiple linear regression adjusted for socioeconomic,
      demographic and cultural factors. RESULTS: Among the age group that was analysed,
      the mean suicide rate was 6.4 cases/100,000 per year in the 2006-2010 period,
      with a male/female ratio of 4.2. The times series showed that there were higher
      suicide rates among people aged 35-64 years and among men aged 15-34 years. The
      ecological analysis showed that the suicide rates were higher in micro-regions
      with a higher proportion of farms run by 35-64 year olds, female workers and on
      farms with better economic indicators (higher farming income, level of
      mechanization and farm area). There was a positive association between the
      Catholic religion and suicide rates. Micro-regions with a greater use of
      pesticides, and with a high proportion of pesticide poisoning had the highest
      suicide rates for all three groups analysed: both genders, men, and women (p
      ranging from 0.01 to p<0.001). CONCLUSION: This study reinforces the hypothesis
      that pesticide use and pesticide poisoning increase the suicide rates. However,
      due to the limitations of the study's ecological design, such as ecological
      fallacy, further appropriately designed studies are needed to confirm the causal
      relationships.

PMID- 24875484
TI  - Occupational exposure to pesticides, nicotine and minor psychiatric disorders
      among tobacco farmers in southern Brazil.
AB  - INTRODUCTION: Exposure to pesticides has been associated with psychiatric
      problems among farm workers, although there is still controversy as to chemical
      types, intensity and forms of exposure that represent risk factors for
      neuropsychological problems. Furthermore, tobacco workers are exposed to dermal
      absorption of nicotine, although its effect on mental health has not yet been
      studied. OBJECTIVES: To identify the prevalence of minor psychiatric disorders
      (MPD) among tobacco farmers and associated factors, paying special attention to
      pesticide and nicotine exposure. METHODS: This is a cross-sectional study with a
      representative sample of tobacco growers, characterizing economic indicators of
      the farms, socio-demographic factors, lifestyle habits and occupational
      exposures. Multivariate analysis was performed using a hierarchical Poisson
      regression model. RESULTS: A total of 2400 tobacco farmers were assessed and MPD
      prevalence was 12%. MPD was higher among women (PR 1.4), workers aged 40 or over,
      tenants/employees (PR 1.8) and those who reported having difficulty in paying
      debts (PR 2.0). Low socioeconomic status was inversely associated with MPD
      prevalence. Tasks involving dermal exposure to pesticides showed risk varying
      between 35% and 71%, whereas tobacco growers on farms using organophosphates had
      50% more risk of MPD than those not exposed to this kind of pesticide. The number
      of pesticide poisoning and green tobacco sickness episodes showed linear
      association with MPD. CONCLUSIONS: The study reinforces the evidence of the
      association between pesticide poisoning and mental health disorders. It also
      points to increased risk of MPD from low socioeconomic status, dermal pesticide
      exposure as well as from exposure to organophosphates. Furthermore, the study
      reveals intense nicotine exposure as a risk for tobacco farmers' mental health.

PMID- 24875486
TI  - Early ischemic blood brain barrier damage: a potential indicator for hemorrhagic
      transformation following tissue plasminogen activator (tPA) thrombolysis?
AB  - Tissue plasminogen activator (tPA) thrombolysis, remains to be the only United
      States Food and Drug Administration (FDA) approved treatment for acute ischemia
      stroke. However, the use of tPA has been profoundly constrained due to its narrow
      therapeutic time window and the increased risk of potentially deadly hemorrhagic
      complications. TPA-associated hemorrhagic transformation (HT) often occurs as a
      result of catastrophic failure of the blood brain barrier (BBB), wherein the
      affected cerebral capillaries can no longer hold blood constituents. Due to its
      direct contribution to edema and HT, reperfusion-associated BBB damage has been
      extensively studied, while BBB damage that occurs within the thrombolytic time
      window is largely neglected. Of note, ischemia-induced BBB damage in the early
      stroke stages is increasingly appreciated to negatively affect the safety and
      efficacy profiles of thrombolytic therapy for ischemic stroke. In this review, we
      discussed the recent findings of spatio-temporal evolution of BBB injury in the
      early stages of cerebral ischemia and its association with intracerebral
      hemorrhage following tPA thrombolysis. The increased understanding of early
      ischemic BBB damage and its close link to tPA-associated HT is of particular
      importance for developing new preventive and therapeutic strategies to reduce the
      hemorrhagic complications in stroke thrombolysis. 

PMID- 24875483
TI  - pT305-CaMKII stabilizes a learning-induced increase in AMPA receptors for ongoing
      memory consolidation after classical conditioning.
AB  - The role of CaMKII in learning-induced activation and trafficking of AMPA
      receptors (AMPARs) is well established. However, the link between the
      phosphorylation state of CaMKII and the agonist-triggered proteasomal degradation
      of AMPARs during memory consolidation remains unknown. Here we describe a novel
      CaMKII-dependent mechanism by which a learning-induced increase in AMPAR levels
      is stabilized for consolidation of associative long-term memory. Six hours after
      classical conditioning the levels of both autophosphorylated pT305-CaMKII and
      GluA1 type AMPAR subunits are significantly elevated in the ganglia containing
      the learning circuits of the snail Lymnaea stagnalis. CaMKIINtide treatment
      significantly reduces the learning-induced elevation of both pT305-CaMKII and
      GluA1 levels and impairs associative long-term memory. Inhibition of proteasomal
      activity offsets the deleterious effects of CaMKIINtide on both GluA1 levels and
      long-term memory. These findings suggest that increased levels of pT305-CaMKII
      play a role in AMPAR-dependent memory consolidation by reducing proteasomal
      degradation of GluA1 receptor subunits. 

PMID- 24875488
TI  - Iron overload is associated with perihematoma edema growth following
      intracerebral hemorrhage that may contribute to in-hospital mortality and long
      term functional outcome.
AB  - Iron overload may contribute to brain damage that involves delayed brain atrophy,
      edema, and neuronal cell death as well as unfavorable outcome following ischemic
      stroke and intracerebral hemorrhage (ICH). This prospective study was performed
      to determine the association of serum ferritin level, an iron storage protein,
      with perihematoma edema (PHE) growth as well as in-hospital mortality and long
      term clinical outcome of patients with ICH. Data was collected from patients with
      ICH from February 2011 to April 2012. Demographic and clinical data were recorded
      and serum ferritin was measured on admission. Brain CT scan was performed on
      admission and 72 hours later. Volume of hematoma and PHE was calculated using
      ABC/2 formula. Functional outcome was assessed using modified Rankin Scale. A
      total of 63 patients were included in this study, of those 11 (17.5%) patients
      died during the first 72 hours of admission. There was a significant correlation
      between PHE growth during first 72 hours of hospitalization and serum ferritin
      (P<0.001) as well as history of diabetes mellitus (P<0.001). PHE growth during
      the first 72-hours of hospitalization and baseline hematoma volume were both
      predictors of in-hospital mortality and poor outcome (P=0.026 and P=0.035,
      respectively). These results indicate the role of iron overload in the
      development of PHE following ICH. However, it seems that serum ferritin level is
      not directly associated with in-hospital mortality and long-term functional
      outcome. 

PMID- 24875487
TI  - Urinary albumin to creatinine ratio as potential biomarker for cerebral
      microvascular disease.
AB  - Elevated urinary albumin to creatinine ratio (ACR) and white matter
      hyperintensity (WMH) volume seen on brain MRI are measures of microvascular
      disease which may have shared susceptibility to metabolic and vascular insults.
      We hypothesized that elevated ACR may be useful as inexpensive biomarker to
      predict presence of cerebral microvascular disease. We assessed the association
      between ACR at study entry and subsequent WMH volume. We evaluated pulse
      pressure, mean arterial pressure, hypertension duration, waist circumference,
      fasting glucose, glomerular filtration rate (GFR) and C-reactive protein (CRP) as
      potential mediators and diabetes as a moderator of the association between ACR
      and WMH. Data were collected at study entry and at follow-up approximately 7
      years later in a multiethnic population sample of 1281 participants (mean age =
      51, SD = 9.5) from Dallas County. Overall, ACR differences were only marginally
      (p = 0.05) associated with subsequent WMH. In mediator analysis, however, ACR
      differences related specifically to arterial pulsatility(beta = 0.010, bootstrap
      95% Confidence Interval (CI): 0.002 to 0.021) and waist circumference (beta = 
      0.004, bootstrap 95% CI: -0.011 to -0.001) were significantly associated with
      WMH. ACR differences related to serum glucose and CRP were not associated with
      WMH. ACR evaluated at the same time as WMH had a higher level of significance (p
      < 0.001) indicating greater utility in predicting current cerebrovascular
      insults.

PMID- 24875489
TI  - A qualitative study of stakeholder views regarding participation in locally
      commissioned enhanced optometric services.
AB  - OBJECTIVES: To explore the views of optometrists, general practitioners (GPs) and
      ophthalmologists regarding the development and organisation of community-based
      enhanced optometric services. DESIGN: Qualitative study using free-text
      questionnaires and telephone interviews. SETTING: A minor eye conditions scheme
      (MECS) and a glaucoma referral refinement scheme (GRRS) are based on accredited
      community optometry practices. PARTICIPANTS: 41 optometrists, 6 ophthalmologists
      and 25 GPs. RESULTS: The most common reason given by optometrists for
      participation in enhanced schemes was to further their professional development;
      however, as providers of 'for-profit' healthcare, it was clear that participants
      had also considered the impact of the schemes on their business. Lack of fit with
      the 'retail' business model of optometry was a frequently given reason for non
      participation. The methods used for training and accreditation were generally
      thought to be appropriate, and participating optometrists welcomed the
      opportunities for ongoing training. The ophthalmologists involved in the MECS and
      GRRS expressed very positive views regarding the schemes and widely acknowledged
      that the new care pathways would reduce unnecessary referrals and shorten patient
      waiting times. GPs involved in the MECS were also very supportive. They felt that
      the scheme provided an 'expert' local opinion that could potentially reduce the
      number of secondary care referrals. CONCLUSIONS: The results of this study
      demonstrated strong stakeholder support for the development of community-based
      enhanced optometric services. Although optometrists welcomed the opportunity to
      develop their professional skills and knowledge, enhanced schemes must also
      provide a sufficient financial incentive so as not to compromise the
      profitability of their business.

PMID- 24875491
TI  - Mind the gap between recommendation and implementation-principles and lessons in
      the aftermath of incident investigations: a semi-quantitative and qualitative
      study of factors leading to the successful implementation of recommendations.
AB  - OBJECTIVES: Using the findings of incident investigations to improve patient
      safety management is well-established and mandatory under Swedish law. This study
      seeks to identify the mechanisms behind successful implementation of the
      recommendations of incident investigations. SETTING: This study was based in a
      university hospital in southern Sweden. PARTICIPANTS: A sample of 55 incident
      investigations from 2008 to 2010 were selected from the hospital's incident
      reporting system by staff in the office of the chief medical officer. These
      investigations were initiated by 23 different commissioning bodies and contained
      289 separate recommendations. We used a three-stage method: content analysis to
      code the recommendations, semi-structured interviews with the commissioning
      bodies focusing on which recommendations had been implemented and why, and data
      analysis of the coded recommendations together with data from the interviews.
      RESULTS: We found that a clear majority (70%) of the recommendations presented to
      the commissioning bodies were targeted at the micro-level of the organisation. In
      nearly half (45%) of all recommendations, actions had been taken and a clear
      majority (73%) of these were at the micro-level. Changes in the management
      positions of the commissioning bodies meant that very little further action was
      taken. Other actions, independent of incident investigations, were often taken
      within the organisation. CONCLUSIONS: We conclude that two principles ('close in
      space' and 'close in time') seem to be important for bridging the gap between
      recommendation and implementation. The micro-level focus was expected because of
      the method of investigation used. Adverse events trigger organisational action
      independently of incident investigations.

PMID- 24875490
TI  - Higher risk of incident hepatitis C virus among young women who inject drugs
      compared with young men in association with sexual relationships: a prospective
      analysis from the UFO Study cohort.
AB  - BACKGROUND: Female injection drug users (IDUs) may report differences in
      injection behaviours that put them at greater risk for hepatitis C virus (HCV).
      Few studies have examined these in association with HCV incidence. METHODS:
      Longitudinal data from a cohort of 417 HCV-uninfected IDU aged 30 or younger were
      analysed. Cox proportional hazards was used to model female sex as a predictor of
      new HCV infection. General estimating equation (GEE) analysis was used to model
      female sex as a predictor of HCV-associated risk behaviour prospectively.
      RESULTS: Women were significantly more likely than men to become infected with
      HCV during study follow-up (HR 1.4, p<0.05), and were also more likely than men
      to report high-risk injecting behaviours, especially in the context of sexual and
      injecting relationships. Sex differences in injecting behaviours appeared to
      explain the relationship between sex and HCV infection. CONCLUSIONS: Young
      women's riskier injection practices lead to their higher rates of HCV infection.
      Further study on the impact of intimate partnership on women's risk behaviour is
      warranted.

PMID- 24875492
TI  - Service configuration, unit characteristics and variation in intervention rates
      in a national sample of obstetric units in England: an exploratory analysis.
AB  - OBJECTIVES: To explore whether service configuration and obstetric unit (OU)
      characteristics explain variation in OU intervention rates in 'low-risk' women.
      DESIGN: Ecological study using funnel plots to explore unit-level variations in
      adjusted intervention rates and simple linear regression, stratified by parity,
      to investigate possible associations between unit characteristics/configuration
      and adjusted intervention rates in planned OU births. Characteristics considered:
      OU size, presence of an alongside midwifery unit (AMU), proportion of births in
      the National Health Service (NHS) trust planned in midwifery units or at home and
      midwifery 'under' staffing. SETTING: 36 OUs in England. PARTICIPANTS: 'Low-risk'
      women with a 'term' pregnancy planning vaginal birth in a stratified, random
      sample of 36 OUs. MAIN OUTCOME MEASURES: Adjusted rates of intrapartum caesarean
      section, instrumental delivery and two composite measures capturing birth without
      intervention ('straightforward' and 'normal' birth). RESULTS: Funnel plots showed
      unexplained variation in adjusted intervention rates. In NHS trusts where
      proportionately more non-OU births were planned, adjusted intrapartum caesarean
      section rates in the planned OU births were significantly higher (nulliparous:
      R(2)=31.8%, coefficient=0.31, p=0.02; multiparous: R(2)=43.2%, coefficient=0.23,
      p=0.01), and for multiparous women, rates of 'straightforward' (R(2)=26.3%,
      coefficient=-0.22, p=0.01) and 'normal' birth (R(2)=17.5%, coefficient=0.24,
      p=0.01) were lower. The size of the OU (number of births), midwifery 'under'
      staffing levels (the proportion of shifts where there were more women than
      midwives) and the presence of an AMU were associated with significant variation
      in some interventions. CONCLUSIONS: Trusts with greater provision of non-OU
      intrapartum care may have higher intervention rates in planned 'low-risk' OU
      births, but at a trust level this is likely to be more than offset by lower
      intervention rates in planned non-OU births. Further research using high quality
      data on unit characteristics and outcomes in a larger sample of OUs and trusts is
      required.

PMID- 24875493
TI  - Glycoligand-targeted core-shell nanospheres with tunable drug release profiles
      from calixarene-cyclodextrin heterodimers.
AB  - Stable core-shell nanospheres self-assemble in water from heterodimers combining
      a hydrophobic calix[4]arene moiety and a hydrophilic beta-cyclodextrin head;
      their potential to encapsulate and provide sustained release of the anticancer
      drug docetaxel and undergo surface post-modification with glycoligands targeting
      the macrophage mannose receptor is discussed. 

PMID- 24875494
TI  - Crystal structure of penicillin-binding protein 3 (PBP3) from Escherichia coli.
AB  - In Escherichia coli, penicillin-binding protein 3 (PBP3), also known as FtsI, is
      a central component of the divisome, catalyzing cross-linking of the cell wall
      peptidoglycan during cell division. PBP3 is mainly periplasmic, with a 23
      residues cytoplasmic tail and a single transmembrane helix. We have solved the
      crystal structure of a soluble form of PBP3 (PBP3(57-577)) at 2.5 A revealing the
      two modules of high molecular weight class B PBPs, a carboxy terminal module
      exhibiting transpeptidase activity and an amino terminal module of unknown
      function. To gain additional insight, the PBP3 Val88-Ser165 subdomain (PBP3(88
      165)), for which the electron density is poorly defined in the PBP3 crystal, was
      produced and its structure solved by SAD phasing at 2.1 A. The structure shows a
      three dimensional domain swapping with a beta-strand of one molecule inserted
      between two strands of the paired molecule, suggesting a possible role in PBP3(57
      577) dimerization.

PMID- 24875495
TI  - Differences in supraspinal and spinal excitability during various force outputs
      of the biceps brachii in chronic- and non-resistance trained individuals.
AB  - Motor evoked potentials (MEP) and cervicomedullary evoked potentials (CMEP) may
      help determine the corticospinal adaptations underlying chronic resistance
      training-induced increases in voluntary force production. The purpose of the
      study was to determine the effect of chronic resistance training on corticospinal
      excitability (CE) of the biceps brachii during elbow flexion contractions at
      various intensities and the CNS site (i.e. supraspinal or spinal) predominantly
      responsible for any training-induced differences in CE. Fifteen male subjects
      were divided into two groups: 1) chronic resistance-trained (RT), (n = 8) and 2)
      non-RT, (n = 7). Each group performed four sets of ~5 s elbow flexion
      contractions of the dominant arm at 10 target forces (from 10%-100% MVC). During
      each contraction, subjects received 1) transcranial magnetic stimulation, 2)
      transmastoid electrical stimulation and 3) brachial plexus electrical
      stimulation, to determine MEP, CMEP and compound muscle action potential (Mmax)
      amplitudes, respectively, of the biceps brachii. All MEP and CMEP amplitudes were
      normalized to Mmax. MEP amplitudes were similar in both groups up to 50% MVC,
      however, beyond 50% MVC, MEP amplitudes were lower in the chronic RT group
      (p<0.05). CMEP amplitudes recorded from 10-100% MVC were similar for both groups.
      The ratio of MEP amplitude/absolute force and CMEP amplitude/absolute force were
      reduced (p<0.012) at all contraction intensities from 10-100% MVC in the chronic
      RT compared to the non-RT group. In conclusion, chronic resistance training
      alters supraspinal and spinal excitability. However, adaptations in the spinal
      cord (i.e. motoneurone) seem to have a greater influence on the altered CE. 

PMID- 24875497
TI  - How big of a threat is needlestick-injury-induced complex regional pain syndrome?
      A "scientific" perspective.
AB  - Complex regional pain syndrome (CRPS), previously known as reflex sympathetic
      dystrophy, is attracting more public attention in Japan which is likely a result
      of the recent upsurge in lawsuits filed against medical institutes. A recent
      court ruling over a case of injection-needlestick-injury induced CRPS has touched
      off serious debates among both medical practitioners and legal professionals.
      Although the court rejected the plaintiff's claims, the high court admitted them
      in view of the evidence and the entire pleadings and ordered the defendant to pay
      compensation. As venipuncture is the most frequently conducted and minimally
      invasive procedure in daily clinical practice, this court decision has attracted
      tremendous interest throughout the nation, alarming medical practitioners, and
      encouraging attorneys. The purpose of this article is twofold: to highlight the
      patient's clinical course in summary based on an unofficial case law report and
      to provide a scientific perspective on this issue based on recent relevant
      articles.

PMID- 24875498
TI  - Posterolateral rotatory instability of the elbow after corrective osteotomy for
      previously asymptomatic cubitus varus deformity.
AB  - BACKGROUND: We identified a subset of patients who had posterolateral rotatory
      instability (PLRI) following corrective osteotomy for asymptomatic cubitus varus
      deformity. We aimed to identify risk factors for PLRI in such patients by
      comparing this subgroup to patients who did not demonstrate PLRI following
      osteotomy. METHODS: We retrospectively reviewed the medical records and
      radiographs of 22 patients with cubitus varus that underwent corrective osteotomy
      at our institution between 2003 and 2010. All patients underwent surgery for
      cosmetic reasons, and no patient reported functional problems such as PLRI or
      ulnar nerve symptoms pre-operatively. We sought to identify differences between
      those that experienced an increase in PLRI after osteotomy (PLRI group) and those
      that did not (non-PLRI group) with regard to demographics, degree of deformity,
      amount of surgical correction, and final outcomes. RESULTS: Five patients had
      PLRI after osteotomy, and all five subsequently underwent lateral ulnar
      collateral ligament reconstruction using a triceps tendon graft. No statistically
      significant difference was observed between the PLRI and non-PLRI groups in terms
      of demographics, degree of deformity, amount of surgical correction, range of
      motion, and final Mayo Elbow Performance Index (MEPI) and the Disabilities of
      Arm, Shoulder, and Hand (DASH) scores. However, the PLRI group had marginally
      greater medial displacement of the distal fragment. CONCLUSIONS: This study
      demonstrates that PLRI can become apparent after corrective osteotomy for cubitus
      varus in the absence of clinical symptoms of instability preoperatively. We
      suggest that careful examination for PLRI should be performed after surgical
      correction for cubitus varus deformity, and surgeons should be prepared to
      proceed with simultaneous reconstruction of the lateral ligaments of the elbow.

PMID- 24875496
TI  - Mapping the global distribution of livestock.
AB  - Livestock contributes directly to the livelihoods and food security of almost a
      billion people and affects the diet and health of many more. With estimated
      standing populations of 1.43 billion cattle, 1.87 billion sheep and goats, 0.98
      billion pigs, and 19.60 billion chickens, reliable and accessible information on
      the distribution and abundance of livestock is needed for a many reasons. These
      include analyses of the social and economic aspects of the livestock sector; the
      environmental impacts of livestock such as the production and management of
      waste, greenhouse gas emissions and livestock-related land-use change; and large
      scale public health and epidemiological investigations. The Gridded Livestock of
      the World (GLW) database, produced in 2007, provided modelled livestock densities
      of the world, adjusted to match official (FAOSTAT) national estimates for the
      reference year 2005, at a spatial resolution of 3 minutes of arc (about 5*5 km at
      the equator). Recent methodological improvements have significantly enhanced
      these distributions: more up-to date and detailed sub-national livestock
      statistics have been collected; a new, higher resolution set of predictor
      variables is used; and the analytical procedure has been revised and extended to
      include a more systematic assessment of model accuracy and the representation of
      uncertainties associated with the predictions. This paper describes the current
      approach in detail and presents new global distribution maps at 1 km resolution
      for cattle, pigs and chickens, and a partial distribution map for ducks. These
      digital layers are made publically available via the Livestock Geo-Wiki
      (http://www.livestock.geo-wiki.org), as will be the maps of other livestock types
      as they are produced. 

PMID- 24875499
TI  - Anatomy of the extensor pollicis brevis associated with an extension mechanism of
      the thumb metacarpophalangeal joint.
AB  - This study aimed to determine whether the extensor pollicis longus (EPL) or
      abductor pollicis longus (APL) can replace the function of thumb extension in
      hands in which the extensor pollicis brevis (EPB) is absent. Cadaver dissection
      was performed to examine anatomical association between the interphalangeal (IP)
      joint and metacarpophalangeal (MP) joint of the thumb, as well as extension
      mechanism in clinical cases. EPB insertion could be classified into eight types,
      and the EPB was absent in 7.6% of all cases. In hands without an EPB, the width
      of the EPL tendon tended to be wider, and the number of APL tendons was
      significantly greater than in hands with an EPB. In hands without an EPB, the EPL
      and APL may replace the function of the EPB. As a result, a greater load is
      imposed on these two tendons than in hands with the EPB.

PMID- 24875500
TI  - Posterior interosseous artery flap: our experience and review of modifications
      done.
AB  - This is a report on the 14 PIA flaps done in our centre for traumatic hand
      defects over both volar and dorsal aspects, as well as thumb reconstruction over
      a six-year period from 2000 to 2007. We were able to achieve reach to the DIPJ
      with the use of fascia extension and better flap survival with more perforators
      captured in the flap.

PMID- 24875501
TI  - Flexor pollicis longus reconstruction using the palmaris longus in anterior
      interosseus nerve syndrome.
AB  - In anterior interosseus nerve syndrome, reconstruction of the paralyzed flexor
      pollicis longus is occasionally required. Traditionally, the brachioradialis has
      been used as a motor, but we utilised the palmaris longus, which is expendable.
      The palmaris longus tendon was transferred in an end-to-side manner, leaving the
      flexor pollicis longus in situ. The procedure was performed in three patients.
      All patients regained a full range of thumb interphalangeal joint motion and an
      average 90% of the pinch strength. The only complication noted was thenar pain
      due to the adhesion of the palmar branch of the median nerve with the transferred
      tendon in one patient. This can be avoided if the interlacing suture was placed
      more proximally. Palmaris longus transfer is a simple technique that gives a
      satisfactory result.

PMID- 24875502
TI  - Structural changes of the carpal tunnel, median nerve and flexor tendons in MRI
      before and after endoscopic carpal tunnel release.
AB  - The purpose of this study is to investigate the structural changes of the carpal
      tunnel, median nerve, and flexor tendons in magnetic resonance imaging (MRI)
      before and after endoscopic carpal tunnel release (ECTR). We studied 36 hands
      undergoing ECTR. In MRI, the cross-sectional area of the carpal tunnel and the
      median nerve at the hamate and the pisiform levels were measured. The distance
      from the volar side of carpal bone to the median nerve or tendons and the volar
      displacement were measured. In post-operative MRI, the transverse carpal ligament
      could not be well delineated and the carpal tunnel was significantly enlarged
      both at the hamate and pisiform levels. The median nerve was enlarged at the
      hamate level. The median nerve and flexor tendons significantly moved to the
      volar side. The volar displacement of the median nerve and flexor digitorum
      superficialis in the long and ring fingers was greater than the other tendons.

PMID- 24875503
TI  - Thumb opposition in severe carpal tunnel syndrome with undetectable APB-CMAP.
AB  - Thumb opposition does not always represent the function of the median nerve due
      to variations in thenar muscle innervation. One hundred and thirty hands of 109
      idiopathic carpal tunnel syndrome (CTS) patients with an undetectable compound
      muscle action potential of the abductor pollicis brevis (APB-CMAP) were
      classified into one of four groups; Type 1 (86.2%) had thenar muscle atrophy and
      could not perform thumb opposition; Type 2 (10.8%) had thenar muscle atrophy but
      could perform thumb opposition; Type 3 (2.3%) did not have thenar muscle atrophy
      and could perform thumb opposition, but needle electromyography of the APB showed
      neurogenic changes and Type 4 (0.8%) had no thenar muscle atrophy, could perform
      thumb opposition, and needle electromyography showed no neurogenic changes. Over
      10% of severe CTS patients have mild or no muscle atrophy and intact thumb
      opposition. The purpose of this study was to investigate the variations in thenar
      muscle innervation in patients with severe CTS.

PMID- 24875505
TI  - A 20-year analysis of hand and wrist research productivity in Asia.
AB  - Bibliometric analyses of the hand and wrist research have previously shown a
      significant increase in research productivity in Asia. We examined the key
      contributors to this change by performing bibliometric analyses regarding hand
      and wrist research in all Asian countries producing significant research.
      Original research articles from 1988 to 2007 were collected from seven English
      language journals based on the impact factor. Trends in research productivity
      were determined by country using linear regression analysis. Compared to the rest
      of the world, Asia produced fewer level I and basic studies, but more level IV
      studies. Significant increase in both research volume and productivity in Asia
      was observed, with Japan, Korea, and Taiwan having the highest aggregate
      productivity in hand and wrist research. From 1988 to 2007, the relative research
      production among Asian countries showed significant change, in contrary to that
      of Europe, Latin American, and the United States.

PMID- 24875506
TI  - Treatment of extra-articular distal radial malunion with percutaneous osteotomy
      and an intramedullary implant.
AB  - PURPOSE: Distal radius malunion is often seen after distal radius fracture. We
      performed a less invasive but secure corrective surgery using an intramedullary
      implant combined with percutaneous osteotomy. The purpose of this study was to
      evaluate the results of this surgical technique. PATIENTS AND METHODS: Three
      patients with malunion of a distal radius fracture were included. We assessed the
      wrist joint disability scores pre-operatively and at the final follow-up an
      average of 21 months after surgery. We also performed radiological assessments of
      volar tilt, radial inclination, and ulnar variance. RESULTS: All three patients
      achieved excellent clinical results with an average joint disability score of
      93.3 at the final follow-up. The radiological parameters improved without any
      post-operative correction loss. DISCUSSION: Intramedullary implant combined with
      percutaneous osteotomy provides sufficient stability after correction of distal
      radius malunion and avoids the complications associated with the use of a volar
      plate.

PMID- 24875504
TI  - Resource utilisation associated with single digit Dupuytren's contracture treated
      with either surgery or injection of collagenase Clostridium histolyticum.
AB  - The gold standard treatment for Dupuytren's contracture is surgical excision of
      the cord. A non-surgical treatment with collagenase clostridium histolyticum
      injection is available but appears costly. OBJECTIVES: To provide data on
      resource consumption related to surgical and non-surgical treatment for
      Dupuytren's contracture. DESIGN AND PARTICIPANTS: Twenty patients with a single
      digit Dupuytren's contracture, 10 treated with surgical excision, and 10 treated
      with a single injection of collagenase. MEASUREMENTS: Minutes spent in theatre,
      number of follow-up appointments, time to skin healing, and patients return to
      normal activities of daily living. RESULTS: The injection group was significantly
      better regarding theatre time (p < 0.0001), follow-up appointments (p = 0.048),
      skin healing time (p < 0.001), and return to normal activities of daily living (p
      = 0.02) than the operated group. CONCLUSIONS: There are significant personal and
      health economic differences between the two methods of treatment which may
      influence local choice.

PMID- 24875507
TI  - Intraosseous xanthoma of the distal radius - a case report.
AB  - An intraosseous xanthoma is a very rare condition. It has an aggressive
      appearance on radiographs mimicking primary or metastatic malignant bone tumors.
      We report a case of intraosseous xanthoma of the distal radius in a 51-year-old
      male with no history of hyperlipidaemia. To the best of our knowledge, this
      condition has not been reported so far in the wrist and forearm region. The
      lesion was successfully excised and at last follow-up, there were no signs of
      recurrence and patient has been symptom-free.

PMID- 24875508
TI  - Sauve-Kapandji procedure in a patient with wrist disarticulation: case report.
AB  - The advantage of preserving the distal radioulnar joint in wrist disarticulation
      is that full forearm rotation is possible if the joint is intact, which improves
      the capability of the amputee. The Sauve-Kapandji procedure has been performed to
      treat rheumatoid or post-traumatic chronic instability and/or arthritis of the
      distal radioulnar joint. We report a patient with wrist disarticulation that
      presented to us with limited supination of the wrist due to an injured distal
      radioulnar joint. We performed the Sauve-Kapandji procedure, and the patient
      could regain functional supination of the forearm without losing the ulnar
      styloid flare that improved prosthetic suspension. This case suggests that the
      Sauve-Kapandji procedure can be performed to maintain the advantage of wrist
      disarticulation even when the initial trauma involves an irreparable injury of
      the distal radioulnar joint. 

PMID- 24875509
TI  - Two cases of proximal pole scaphoid fracture accompanied by lunate fracture.
AB  - We experienced two cases of simultaneous fracture of the scaphoid and the lunate.
      In two cases, both scaphoid and lunate fractures existed on the same plane, which
      may help us to understand the mechanism of proximal fracture of the scaphoid. 

PMID- 24875510
TI  - A case report of trigger wrist associated with carpal tunnel syndrome caused by
      an intramuscular lipoma.
AB  - Triggering at the wrist with finger movement is an uncommon presentation. We
      present the case of a 46 year old male with painful wrist triggering with
      associated carpal tunnel syndrome caused by an intramuscular lipoma of the
      lumbrical muscle. As far as we are aware this is only the second documented case
      of wrist triggering caused by an intramuscular limpoma. Surgical removal of the
      tumour led to a resolution of the patients symptoms. We review the literature and
      discuss other published cases of this rare presentation.

PMID- 24875511
TI  - Spontaneous rupture of EPL and ECRB tendons in a washerwoman: an unusual
      phenomenon.
AB  - Spontaneous rupture of the extensor pollicis longus (EPL) tendon is rare, and
      spontaneous non-traumatic rupture of both extensor pollicis longus (EPL) and
      extensor carpi radialis brevis (ECRB) tendons is not reported in literature.
      Rupture of EPL is usually associated with rheumatoid arthritis, systemic or local
      steroid injections, fractures of the wrist and repetitive and excessive abnormal
      motion of the wrist joint. We describe a case of spontaneous rupture of the EPL
      and ECRB tendons in a female patient, washerwoman by occupation, with no
      predisposing factor. Exploration of the tendons along with end to end tendon
      repair was done with excellent results. We describe the possible mechanism of the
      injury and result after one year follow up.

PMID- 24875512
TI  - A case of recurring multifocal giant cell tumour of the tendon sheath in a child.
AB  - Giant cell tumour of the tendon sheath is rare in children. We present an unusual
      case of a recurring multifocal giant cell tumour of the tendon sheath in the hand
      and wrist of an 11-year-old boy. We are not aware of any similar report in the
      literature.

PMID- 24875513
TI  - Mycobacterium kanasii flexor tenosynovitis of the finger.
AB  - We report an extreme case of Mycobacterium kanasii flexor tenosynovitis with
      flexor tendon rupture in a healthy 65-year-old left-hand dominant Caucasian
      housewife. This case highlights the diagnostic conundrum of atypical mycobacteria
      infections due to their insidious presentation, the need for a high index of
      suspicion to prevent worsening or delaying the diagnosis from inappropriate
      steroid use and that these infections can occur in otherwise healthy individuals.

PMID- 24875514
TI  - Congenital defects of the flexor digitorum profundus tendon of the little finger.
AB  - The cases of two patients, a four-year-old boy and an eight-year-old boy, who had
      been incapable of active flexion of the little finger since birth, are presented.
      They were capable of active flexion of the metacarpophalangeal (MP) joint, but
      not of the proximal interphalangeal (PIP) and distal interphalangeal (DIP)
      joints. They were diagnosed with a defect of the flexor digitorum profundus (FDP)
      tendon of the little finger and underwent surgery. In both cases, the FDP tendon
      turned into fibrous tissue proximal to the palm and lost continuity on this side.
      Reconstruction was performed by making an end-to-side anastomosis of the residual
      proximal end of the FDP tendon to the FDP tendon of the ring finger in the palmar
      region. Although one patient required repeated surgery due to post-operative
      tendon adhesion, good outcomes were achieved, with both patients becoming capable
      of active flexion.

PMID- 24875515
TI  - Atypical subcutaneous granuloma annulare on the digit: a case report.
AB  - Subcutaneous granuloma annulare is a benign inflammatory disorder consisting of
      deep dermal or subcutaneous nodules, and frequently occurring in the extremities
      and scalp in children. The occurrence of aggregated multiple nodules in a digit
      is quite atypical. This is a report of an eight-year-old girl who presented with
      increasingly asymptomatic multiple nodules on her middle finger over a period of
      six months. Definitive diagnosis of subcutaneous granuloma annulare was achieved
      with surgical biopsy and no aggressive growth subsequently and showed a tendency
      toward spontaneous resolution.

PMID- 24875516
TI  - Sea urchin spine arthritis of the proximal interphalangeal joint of the hand:
      radiological, intraoperative and histopathological findings.
AB  - Penetrating sea urchin spine injuries, can lead to devastating, irreversible
      consequences. Persistent inflammation, cutaneous granuloma, neuroma,
      tenosynovitis, arthritis and destructive arthritis, leading to permanent loss of
      function and digit amputation, can occur. We present a case of a patient who
      developed sea urchin spine arthritis of the proximal interphalangeal joint. Only
      17 cases of sea urchin spine arthritis of the hand have been documented in the
      medical literature. However, in this case, the article also includes sequential
      radiographs, histopathological slides, and intra-operative photographs.

PMID- 24875517
TI  - Intraosseous epidermoid cyst discovered in the distal phalanx of a thumb: a case
      report.
AB  - Intraosseous epidermoid cyst is considered a rare benign inclusion cyst found
      mainly in the skull and phalanges. Once the cyst is differentiated from other
      similar lesions, the cyst can be treated with simple curettage, seldom requiring
      additional managements. We experienced this rare case that had been treated
      successfully without complication.

PMID- 24875518
TI  - A new building block: costo-osteochondral graft for intra-articular incongruity
      after distal radius fracture.
AB  - Even with the invention of locking plates, intra-articular fractures of distal
      radius with extreme comminution remain a challenge for orthopaedic surgeons.
      Osteochondral graft is a potential choice to reconstruct the articular defect. We
      report a patient who had a fracture of distal radius with costo-osteochondral
      graft for articular reconstruction which has not yet been described in the
      English literature. At nine-year follow-up, he was pain free and had full range
      of movement of the wrist. The authors suggest that costo-osteochondral graft
      could be an option with satisfactory result.

PMID- 24875519
TI  - Wrist arthrodesis in children - a new technique: case presentation.
AB  - Wrist arthrodesis is exceptionally performed in children. The main indication is
      severe wrist flexion contracture resulting from Volkmann's ischaemia or
      spasticity. In such cases, a proximal row carpectomy is usually necessary to
      allow the wrist to be positioned in neutral position. In young children, it is
      essential to preserve the distal radius growth plate, to prevent physeal closure.
      In these very particular indications, with high stresses along the stretched
      palmar soft-tissues, Kirschner wire fixation provides poor stability, and plate
      fixation is contra-indicated. Radio-metacarpal external fixation is an excellent
      alternative, preserving the distal radius growth plate and offering sufficient
      stability. This technique was used in a seven-year-old girl suffering from
      Volkmann's ischaemic contracture, treated by first carpal bone resection and
      subsequent arthrodesis with radio-metacarpal external fixation. Bone healing was
      achieved in three months, with a five years follow-up preservation of the distal
      radius growth plate.

PMID- 24875520
TI  - Arthroscopic assisted percutaneous screw fixation of Bennett's fracture.
AB  - Several techniques are used for fixation of Bennett's fractures. The aim of this
      study was to assess a technique of arthroscopic-assisted reduction and
      percutaneous cannulated screw fixation of Bennett's fractures. Seven patients
      (mean age 29 years) with three fractures Type I and four fractures Type II
      according to Gedda were operated under arthroscopic lavage, fluoroscopic screw
      fixation, and arthroscopic control of the joint reduction. Arthroscopy, showed
      satisfactory joint reduction in all cases. At 4.5 months, the mean pain score was
      1 (0-4), QuickDASH 15 (0-61), and Kapandji score 9 (5-10). Compared to the
      contralateral side, first web opening was 86% (58-100), key pinch 73% (45-89),
      grip strength, and 85% (40-100). Four secondary displacements were noted, two of
      which had a step of more than 1 mm. Our results showed that the use of
      arthroscopy for percutaneous screw fixation of Bennett's fractures facilitates
      joint reduction but does not guarantee stability of fixation.

PMID- 24875521
TI  - Usefulness of braided polyblend polyethylene suture material for flexor tendon
      repair in zone II by the side-locking loop technique.
AB  - Flexor tendon injuries in zone II were treated in 14 fingers of 13 patients with
      our method. Firstly, a 2-strand core suture was made by the side-locking loop
      technique using a USP 2-0-sized braided polyblend polyethylene suture, then 7
      strand peripheral cross-stitches were added using a USP 5-0-sized monofilament
      nylon suture. Post-operative exercises included passive flexion and extension
      without external fixation on the next day of surgery. Average follow-up
      observation period was 18 months. As results, the Strickland method of assessment
      for surgical outcome showed excellent in eight digits and good in five digits,
      though there was a poor outcome in one digit. Our suture method enabled early
      post-operative mobilisation exercise without using a splint, while preventing
      adhesion between the repaired tendon and peripheral tissues, which is considered
      to provide far greater ultimate tensile strength and a smaller gap at the sutured
      site than by the conventional method.

PMID- 24875522
TI  - Surgical tips to optimize digital flexor sheath washout.
AB  - Flexor sheath infection is a hand surgery emergency, and emergent washout is the
      accepted practice to prevent digital amputation. The authors describe surgical
      steps to optimize flexor sheath irrigation. 

PMID- 24875523
TI  - Management of flexor tendon injuries - Part 1: Australian contributions.
AB  - This review article describes the contribution of Australian authors to the basic
      science and clinical management of flexor tendon injuries.

PMID- 24875525
TI  - Wrist arthroplasty: where do we stand today? A review of historic and
      contemporary designs.
AB  - Earlier generations of wrist arthroplasty were limited to low demand patients.
      Bone fixation problems, excessive wear, and adverse designs resulting in
      loosening, imbalance, and dislocation led to the withdrawal of a number of
      models. Contemporary wrist prostheses aim at replacing wrist arthrodesis in the
      majority of patients with radiocarpal destruction, including high demand cases.
      Contraindications are wrist imbalance, insufficient soft tissue, or bone stock
      and infection. Various designs, fixation principles, bearing materials, and
      articulations have been employed. Some of the devises (RE-MOTIONTM, Motec((r)))
      demonstrate promising short- to midterm results, and calls for cautious optimism.

PMID- 24875524
TI  - Management of flexor tendon injuries - Part 2: current practice in Australia and
      guidelines for training young surgeons.
AB  - INTRODUCTION: This study aims to gain a better understanding of current practice
      for the surgical management and rehabilitation of flexor tendon injuries in
      Australia, with the intent of establishing common guidelines for training of
      young surgeons. METHODS: A survey was distributed to the membership of the
      Australian Hand Surgery Society to determine whether a consensus could be
      obtained for: suture material and gauge; core and epitenon suture techniques;
      sheath and pulley management; and post-operative protocols for primary flexor
      tendon repair. RESULTS: The predominant materials used for core suture are
      TicronTM Suture (Tyco Healthcare Group LP, Norwalk, Connecticut, USA) (34%) and
      EthibondTM Polyester Suture (Ethicon, Somerville, New Jersey, USA) (24%). The two
      core suture configurations commonly used are the Adelaide (45%) and Kessler (32%)
      repair. The predominant materials used for epitendinous sutures are 6-0 ProleneTM
      Polypropylene Suture (Ethicon, Somerville, New Jersey, USA) (56%), 5-0 ProleneTM
      (21%) and 6-0 EthilonTM Nylon Suture (Ethicon, Somerville, New Jersey, USA)
      (13%); and the majority (63%) use a running epitendinous technique. The
      management of critical pulleys is variable, with 89% prepared to perform some
      release of A2 and A4 pulleys. Rehabilitation protocols vary widely, with 24% of
      respondents using the same method for all patients, while 76% tailor their
      approach to each patient. Some component of active motion was used by most.
      DISCUSSION: There exists some consensus on the management of flexor tendon
      injuries in Australia. However, the management of critical pulleys and methods of
      post-operative rehabilitation remain varied. For the training of young surgeons,
      a majority advise a 3-0 gauge braided polyester core suture of four strands,
      combined with a 6-0 ProleneTM simple running epitendinous suture for increased
      tendon repair strength and smooth glide. Trainees should attempt to retain the
      integrity of the A2 and A4 pulleys. Post-operative rehabilitation should include
      a component of active flexion.

PMID- 24875526
TI  - Understanding Z plasties - deepening of webspace on chicken foot model.

PMID- 24875527
TI  - Response to: Beware the volar ulnar fragment in a comminuted Bartons fracture.

PMID- 24875528
TI  - The magic of hands: India's IFSSH legacy in schools.

PMID- 24875529
TI  - Gold-mercaptopropionic acid-polyethylenimine composite based DNA sensor for early
      detection of rheumatic heart disease.
AB  - The first gold-mercaptopropionic acid-polyethylenimine composite based
      electrochemical DNA biosensor was fabricated for the early detection of
      Streptococcus pyogenes infection in humans causing rheumatic heart disease (heart
      valve damage). No biosensor is available for the detection of rheumatic heart
      disease (RHD). Therefore, the mga gene based sensor was developed by the covalent
      immobilization of a 5'-carboxyl modified single stranded DNA probe onto the gold
      composite electrode. The immobilized probe was hybridized with the genomic DNA (G
      DNA) of S. pyogenes from throat swabs and the electrochemical response was
      measured by cyclic voltammetry (CV), differential pulse voltammetry (DPV) and
      electrochemical impedance (EI). Covalent immobilization of the probe onto the
      gold composite and its hybridization with G-DNA was characterized by FTIR and
      SEM. The sensitivity of the sensor was 110.25 MUA cm(-2) ng(-1) with DPV and the
      lower limit of detection was 10 pg per 6 MUL. The sensor was validated with
      patient throat swab samples and results were compared with available methods. The
      sensor is highly specific to S. pyogenes and can prevent damage to heart valves
      by the early detection of the infection in only 30 min. 

PMID- 24875530
TI  - Venus kinase receptors control reproduction in the platyhelminth parasite
      Schistosoma mansoni.
AB  - The Venus kinase receptor (VKR) is a single transmembrane molecule composed of an
      intracellular tyrosine kinase domain close to that of insulin receptor and an
      extracellular Venus Flytrap (VFT) structure similar to the ligand binding domain
      of many class C G protein coupled receptors. This receptor tyrosine kinase (RTK)
      was first discovered in the platyhelminth parasite Schistosoma mansoni, then in a
      large variety of invertebrates. A single vkr gene is found in most genomes,
      except in S. mansoni in which two genes Smvkr1 and Smvkr2 exist. VKRs form a
      unique family of RTKs present only in invertebrates and their biological
      functions are still to be discovered. In this work, we show that SmVKRs are
      expressed in the reproductive organs of S. mansoni, particularly in the ovaries
      of female worms. By transcriptional analyses evidence was obtained that both
      SmVKRs fulfill different roles during oocyte maturation. Suppression of Smvkr
      expression by RNA interference induced spectacular morphological changes in
      female worms with a strong disorganization of the ovary, which was dominated by
      the presence of primary oocytes, and a defect of egg formation. Following
      expression in Xenopus oocytes, SmVKR1 and SmVKR2 receptors were shown to be
      activated by distinct ligands which are L-Arginine and calcium ions,
      respectively. Signalling analysis in Xenopus oocytes revealed the capacity of
      SmVKRs to activate the PI3K/Akt/p70S6K and Erk MAPK pathways involved in cellular
      growth and proliferation. Additionally, SmVKR1 induced phosphorylation of JNK (c
      Jun N-terminal kinase). Activation of JNK by SmVKR1 was supported by the results
      of yeast two-hybrid experiments identifying several components of the JNK pathway
      as specific interacting partners of SmVKR1. In conclusion, these results
      demonstrate the functions of SmVKR in gametogenesis, and particularly in
      oogenesis and egg formation. By eliciting signalling pathways potentially
      involved in oocyte proliferation, growth and migration, these receptors control
      parasite reproduction and can therefore be considered as potential targets for
      anti-schistosome therapies.

PMID- 24875532
TI  - Decreased CD34+ cell number is correlated with cardiac dysfunction in patients
      with acute exacerbation of COPD.
AB  - BACKGROUND AND PURPOSE: Acute exacerbation of chronic obstructive pulmonary
      disease (AECOPD) is associated with a higher risk of cardiovascular disease
      (CVD). Previous studies have indicated that the reduction of bone marrow-derived
      multipotent progenitors (CD34+ cells) may lead to reduced vascular repair
      capacity and may help to identify patients that pose an increased cardiovascular
      risk. However, the relationship between CD34+cells and CVD risk in AECOPD remains
      unclear. The aim of the present study was to assess CD34+ cell counts and their
      relationship with classical adverse cardiac outcome predictors in AECOPD.
      METHODS: For our study, 27 patients with AECOPD (GOLD stage III, IV), 26 with
      stable COPD (GOLD stage III, IV), and 24 healthy controls were enrolled. CD34+
      cells were enumerated, and plasma concentrations of N-terminal pro-B-type
      natriuretic peptide (NT-proBNP), a systemic inflammation marker (high-sensitivity
      C-reactive protein, hsCRP) and mobilisation marker (matrix metalloproteinase-9,
      MMP-9), were measured. Echocardiography was performed to evaluate cardiac
      dysfunction and pulmonary hypertension. RESULTS: Compared with healthy controls,
      AECOPD patients had a significantly decreased CD34+ cell count (5.1 +/- 2.6
      versus 9.4 +/- 3.6 * 103/ml), especially in patients with a prior history of
      acute exacerbation. For patients with AECOPD, the CD34+ cell count was inversely
      correlated with NT-proBNP levels, pulmonary artery systolic pressure (PASP) and
      resting heart rate, and positively correlated with left ventricular ejection
      fraction (LVEF). In all three groups, CD34+ cell count was negatively correlated
      with hsCRP. CONCLUSIONS: The circulating CD34+ cell count was decreased and
      correlated with cardiac dysfunction in AECOPD patients, and thus may account for
      the increased cardiovascular risk in this population.

PMID- 24875533
TI  - Biomarkers in acute respiratory distress syndrome: from pathobiology to improving
      patient care.
AB  - Acute respiratory distress syndrome (ARDS) is a clinical syndrome characterized
      by alveolar flooding with protein-rich pulmonary edema fluid. Despite an improved
      understanding of ARDS pathogenesis, our ability to predict the development of
      ARDS and risk-stratify patients with the disease remains limited. Biomarkers may
      help identify patients at highest risk of developing ARDS, assess response to
      therapy, predict outcome, and optimize enrollment in clinical trials. This review
      begins with a general description of biomarker use in clinical medicine. We then
      review evidence that supports the value of various ARDS biomarkers organized by
      the cellular injury processes central to ARDS development: endothelial injury,
      epithelial injury, disordered inflammation and coagulation, fibrosis, and
      apoptosis. Finally, we summarize the growing contributions of genomic and
      proteomic research and suggest ways in which the field may evolve in the coming
      years. 

PMID- 24875531
TI  - Ribosomal protein mutations induce autophagy through S6 kinase inhibition of the
      insulin pathway.
AB  - Mutations affecting the ribosome lead to several diseases known as
      ribosomopathies, with phenotypes that include growth defects, cytopenia, and bone
      marrow failure. Diamond-Blackfan anemia (DBA), for example, is a pure red cell
      aplasia linked to the mutation of ribosomal protein (RP) genes. Here we show the
      knock-down of the DBA-linked RPS19 gene induces the cellular self-digestion
      process of autophagy, a pathway critical for proper hematopoiesis. We also
      observe an increase of autophagy in cells derived from DBA patients, in CD34+
      erythrocyte progenitor cells with RPS19 knock down, in the red blood cells of
      zebrafish embryos with RP-deficiency, and in cells from patients with Shwachman
      Diamond syndrome (SDS). The loss of RPs in all these models results in a marked
      increase in S6 kinase phosphorylation that we find is triggered by an increase in
      reactive oxygen species (ROS). We show that this increase in S6 kinase
      phosphorylation inhibits the insulin pathway and AKT phosphorylation activity
      through a mechanism reminiscent of insulin resistance. While stimulating RP
      deficient cells with insulin reduces autophagy, antioxidant treatment reduces S6
      kinase phosphorylation, autophagy, and stabilization of the p53 tumor suppressor.
      Our data suggest that RP loss promotes the aberrant activation of both S6 kinase
      and p53 by increasing intracellular ROS levels. The deregulation of these
      signaling pathways is likely playing a major role in the pathophysiology of
      ribosomopathies.

PMID- 24875534
TI  - Targeting Nrf2-Keap1 signaling for chemoprevention of skin carcinogenesis with
      bioactive phytochemicals.
AB  - The incidence of skin cancer is increasing worldwide. Over the last several
      decades, attention has been focused on understanding the molecular basis of skin
      carcinogenesis and identifying substances for use in chemoprevention of skin
      cancer. Reactive oxygen species generated by chemical carcinogens or UV
      irradiation play a key role in skin tumorigenesis. Multiple lines of evidence
      suggest that cellular antioxidant and/or phase-2 detoxification enzymes,
      collectively known as cytoprotective proteins, can protect against skin
      carcinogenesis. A redox sensitive transcription factor, nuclear factor-erythroid
      related factor-2 (Nrf2), is a master regulator of transcriptional activation of
      genes encoding cytoprotective proteins. Many chemopreventive phytochemicals are
      known to activate Nrf2 either by oxidative or covalent modification of its
      cytosolic repressor Kelch-like ECH-associated protein (Keap1) or by
      phosphorylation of Nrf2. Upon activation, Nrf2 translocates to the nucleus and
      binds to the antioxidant response element (ARE) located in the promoter regions
      of genes encoding cytoprotective proteins. Mice genetically deficient in Nrf2 are
      highly susceptible to chemically induced skin tumorigenesis and are less
      responsive to the cytoprotective effects of some chemopreventive phytochemicals.
      This article highlights the Nrf2-ARE signaling as a prime target for
      chemoprevention of skin cancer with some phytochemicals. 

PMID- 24875535
TI  - Novel dose-dependent alterations in excitatory GABA during embryonic development
      associated with lead (Pb) neurotoxicity.
AB  - Lead (Pb) is a heavy metal that is toxic to numerous physiological processes. Its
      use in industrial applications is widespread and results in an increased risk of
      human environmental exposure. The central nervous system (CNS) is most sensitive
      to Pb exposure during early development due to rapid cell proliferation and
      migration, axonal growth, and synaptogenesis. One of the key components of CNS
      development is the Gamma-aminobutyric acid (GABA)-ergic system. GABA is the
      primary inhibitory neurotransmitter in the adult brain. However, during
      development GABA acts as an excitatory neurotrophic factor which contributes to
      these cellular processes. Multiple studies report effects of Pb on GABA in the
      mature brain; however, little is known regarding the adverse effects of Pb
      exposure on the GABAergic system during embryonic development. To characterize
      the effects of Pb on the GABAergic system during development, zebrafish embryos
      were exposed to 10, 50, or 100 ppb Pb or a control treatment. Tissue up-take,
      gross morphological alterations, gene expression, and neurotransmitter levels
      were analyzed. Analysis revealed that alterations in gene expression throughout
      the GABAergic system and GABA levels were dose and developmental time point
      specific. These data provide a framework for further analysis of the effects of
      Pb on the GABAergic system during the excitatory phase and as GABA transitions to
      an inhibitory neurotransmitter during development.

PMID- 24875536
TI  - Inhibition of cathepsin S induces autophagy and apoptosis in human glioblastoma
      cell lines through ROS-mediated PI3K/AKT/mTOR/p70S6K and JNK signaling pathways.
AB  - Cathepsin S is a lysosomal cysteine protease that is overexpressed in various
      cancer models and plays important role in tumorigenesis, however the mechanisms
      are unclear. In the present study, we found that inhibition of cathepsin S
      induced autophagy and mitochondrial apoptosis in human glioblastoma cells.
      Blockade of autophagy by either a chemical inhibitor or RNA interference
      attenuated cathespin S inhibition-induced apoptosis. Furthermore, autophagy and
      apoptosis induction was dependent on the suppression of phosphatidylinositide 3
      kinases/protein kinase B/mammalian target of rapamycin/p70S6 kinase
      (PI3K/AKT/mTOR/p70S6K) signaling pathway and activation of c-Jun N-terminal
      kinase (JNK) signaling pathway. In addition, reactive oxygen species (ROS) served
      as an upstream of PI3K/AKT/mTOR/p70S6K and JNK signaling pathways. In conclusion,
      the current study revealed that cathepsin S played an important role in the
      regulation of autophagy and apoptosis in human glioblastoma cells. 

PMID- 24875537
TI  - Inhibition of dihydroceramide desaturase activity by the sphingosine kinase
      inhibitor SKI II.
AB  - Sphingosine kinase inhibitor (SKI) II has been reported as a dual inhibitor of
      sphingosine kinases (SKs) 1 and 2 and has been extensively used to prove the
      involvement of SKs and sphingosine-1-phosphate (S1P) in cellular processes.
      Dihydroceramide desaturase (Des1), the last enzyme in the de novo synthesis of
      ceramide (Cer), regulates the balance between dihydroceramides (dhCers) and Cers.
      Both SKs and Des1 have interest as therapeutic targets. Here we show that SKI II
      is a noncompetitive inhibitor (Ki = 0.3 MUM) of Des1 activity with effect also in
      intact cells without modifying Des1 protein levels. Molecular modeling studies
      support that the SKI II-induced decrease in Des1 activity could result from
      inhibition of NADH-cytochrome b5 reductase. SKI II, but not the SK1-specific
      inhibitor PF-543, provoked a remarkable accumulation of dhCers and their
      metabolites, while both SKI II and PF-543 reduced S1P to almost undetectable
      levels. SKI II, but not PF543, reduced cell proliferation with accumulation of
      cells in the G0/G1 phase. SKI II, but not PF543, induced autophagy. These overall
      findings should be taken into account when using SKI II as a pharmacological
      tool, as some of the effects attributed to decreased S1P may actually be caused
      by augmented dhCers and/or their metabolites. 

PMID- 24875539
TI  - Loss of hydroxyl groups from the ceramide moiety can modify the lateral diffusion
      of membrane proteins in S. cerevisiae.
AB  - In the yeast Saccharomyces cerevisiae, structural diversities of complex
      sphingolipids [inositol phosphorylceramide (IPC), mannosylinositol
      phosphorylceramide, and mannosyldiinositol phosphorylceramide] are often observed
      in the presence or absence of hydroxyl groups on the C-4 position of long-chain
      base (C4-OH) and the C-2 position of very long-chain fatty acids (C2-OH), but the
      biological significance of these groups remains unclear. Here, we evaluated
      cellular membrane fluidity in hydroxyl group-defective yeast mutants by
      fluorescence recovery after photobleaching. The lateral diffusion of enhanced
      green fluorescent protein-tagged hexose transporter 1 (Hxt1-EGFP) was influenced
      by the absence of C4-OH and/or C2-OH. Notably, the fluorescence recovery of Hxt1
      EGFP was dramatically decreased in the sur2Delta mutant (absence of C4-OH) under
      the csg1Deltacsh1Delta background, in which mannosylation of IPC is blocked
      leading to IPC accumulation, while the recovery in the scs7Delta mutant (absence
      of C2-OH) under the same background was modestly decreased. In addition, the
      amount of low affinity tryptophan transporter 1 (Tat1)-EGFP was markedly
      decreased in the sur2Deltacsg1Deltacsh1Delta mutant and accumulated in
      intracellular membranes in the scs7Deltacsg1Deltacsh1Delta mutant without
      altering its protein expression. These results suggest that C4-OH and C2-OH are
      most probably critical factors for maintaining membrane fluidity and proper
      turnover of membrane molecules in yeast containing complex sphingolipids with
      only one hydrophilic head group.

PMID- 24875538
TI  - Enriched endogenous omega-3 fatty acids in mice protect against global ischemia
      injury.
AB  - Transient global cerebral ischemia, one of the consequences of cardiac arrest and
      cardiovascular surgery, usually leads to delayed death of hippocampal cornu
      Ammonis1 (CA1) neurons and cognitive deficits. Currently, there are no effective
      preventions or treatments for this condition. Omega-3 (omega-3) PUFAs have been
      shown to have therapeutic potential in a variety of neurological disorders. Here,
      we report that the transgenic mice that express the fat-1 gene encoding for omega
      3 fatty acid desaturase, which leads to an increase in endogenous omega-3 PUFAs
      and a concomitant decrease in omega-6 PUFAs, were protected from global cerebral
      ischemia injury. The results of the study show that the hippocampal CA1 neuronal
      loss and cognitive deficits induced by global ischemia insult were significantly
      less severe in fat-1 mice than in WT mice controls. The protection against global
      cerebral ischemia injury was closely correlated with increased production of
      resolvin D1, suppressed nuclear factor-kappa B activation, and reduced generation
      of pro-inflammatory mediators in the hippocampus of fat-1 mice compared with WT
      mice controls. Our study demonstrates that fat-1 mice with high endogenous omega
      3 PUFAs exhibit protective effects on hippocampal CA1 neurons and cognitive
      functions in a global ischemia injury model.

PMID- 24875543
TI  - Recessive mutations in CAKUT and VACTERL association.
AB  - Understanding the complex genetic makeup underlying congenital anomalies of the
      kidney and urinary tract (CAKUT) is of primary importance to improve diagnosis,
      stratify risk for later-onset complications, and develop therapeutic strategies.
      Saisawat et al. used homozygosity mapping coupled with next-generation sequencing
      to identify recessive mutations in TRAP1 in families with isolated CAKUT and with
      VACTERL association. This study points to a novel player in kidney development,
      possibly affecting apoptosis and endoplasmic reticulum stress signaling. 

PMID- 24875540
TI  - Characterisation of cytoplasmic DNA complementary to non-retroviral RNA viruses
      in human cells.
AB  - The synthesis and subsequent genomic integration of DNA that is complementary to
      the genomes of non-retroviral RNA viruses are rarely observed. However, upon
      infection of various human cell lines and primary fibroblasts with the vesicular
      stomatitis virus (VSV), we detected DNA complementary to the VSV RNA. The VSV DNA
      was detected in the cytoplasm as single-stranded DNA fully complementary to the
      viral mRNA from the poly(A) region to the 7-methyl guanosine cap. The formation
      of this DNA was cell-dependent. Experimentally, we found that the transduction of
      cells that do not produce VSV DNA with the long interspersed nuclear element 1
      and their infection with VSV could lead to the formation of VSV DNA. Viral DNA
      complementary to other RNA viruses was also detected in the respective infected
      human cells. Thus, the genetic information of the non-retroviral RNA virus genome
      can flow into the DNA of mammalian cells expressing LINE-1-like elements. 

PMID- 24875544
TI  - Hydrogen sulfide to the rescue in obstructive kidney injury.
AB  - Hydrogen sulfide is a gasotransmitter with far-reaching effects on cell function.
      Studies show that, depending on the context, hydrogen sulfide can function as an
      ameliorative agent or as a mediator of kidney injury. 

PMID- 24875545
TI  - Decrease of muscle volume in chronic kidney disease: the role of mitochondria in
      skeletal muscle.
AB  - Reduced muscle volume and impaired exercise endurance are well-documented
      phenomena in chronic kidney disease, and the relevant molecular mechanisms have
      been gradually unveiled. Tamaki et al. demonstrate a reduction of mitochondria
      content in skeletal muscles as a novel mechanism of reduced exercise endurance in
      renal insufficiency. In addition, they show that a high-protein diet reduces
      exercise endurance through an inhibition of muscle pyruvate dehydrogenase. 

PMID- 24875546
TI  - Enigmatic Cassandra: renal FGF23 formation in polycystic kidney disease.
AB  - Fibroblast growth factor 23 (FGF23) counteracts phosphate excess and tissue
      calcification. Phosphate intake, Ca(2+), parathyroid hormone, and 1,25
      dihydroxyvitamin D3 (1,25(OH)2D3) stimulate FGF23 release from bone. FGF23
      inhibits renal 1,25(OH)2D3 formation and phosphate reabsorption. Spichtig and
      colleagues demonstrate that FGF23 is generated in rodent polycystic kidneys,
      leading to an increase in plasma FGF23 concentration before reduction in kidney
      function. FGF23 fails to appreciably downregulate renal phosphate transporter and
      1alpha-25OH-vitamin D hydroxylase activities. Unraveling underlying mechanisms
      may open diagnostic and therapeutic opportunities. 

PMID- 24875547
TI  - Death from cancer: a sobering truth for patients with kidney transplants.
AB  - Cancer is a major cause of morbidity among those with kidney transplants.
      Farrugia et al. examined the overall and site-specific risk of cancer death among
      kidney transplant recipients. Cancer outcomes, particularly for those with a
      history of cancer prior to transplantation, are poor. The overall risk of death
      attributed to cancer in patients with kidney transplants is increased at least
      tenfold over that in cancer patients in the general population. 

PMID- 24875548
TI  - Thrombo-prevention in membranous nephropathy: a new tool for decision making?
AB  - Thromboembolic events occur in primary membranous nephropathy, especially when
      serum albumin is less than 2.8 g/dl. In such patients, a conundrum arises
      concerning anticipated benefits and risks when a prophylactic oral anticoagulant
      is considered. Lee et al. describe a flexible Markov decision tree program to aid
      decision making. Its application to individual patients will probably be useful,
      but physicians will need to assess patients' tolerance for the benefit-to-risk
      ratio, considering the many factors bearing on the risk of thromboembolic events
      and/or serious bleeding.

PMID- 24875549
TI  - Within-patient variability in immunosuppressive drug exposure as a predictor for
      poor outcome after transplantation.
AB  - Within-patient variability in immunosuppressive drug exposure is easily
      identified by measurement of drug concentrations at the outpatient clinic.
      Fluctuating levels despite a stable drug dose can be observed in a substantial
      proportion of patients. It has now been shown that this within-patient
      variability is a predictor for poor long-term outcome after transplantation.
      Nonadherence most likely is an important determinant of variability, and
      strategies to tackle nonadherence are being developed. 

PMID- 24875550
TI  - The author replies.

PMID- 24875551
TI  - Elevated soluble urokinase receptors in focal segmental glomerulosclerosis: a
      role for IL-2?

PMID- 24875552
TI  - Increasing mortality by living kidney donation?: the devil is in the details.

PMID- 24875553
TI  - The authors reply:.

PMID- 24875554
TI  - Levels of haloacetic acids in tap water in an urban Australian city and its
      relevance to autosomal dominant polycystic kidney disease.

PMID- 24875559
TI  - CYP24A1 mutation leading to nephrocalcinosis.

PMID- 24875560
TI  - A flagellated protozoa in the urine: other than Trichomonas.

PMID- 24875561
TI  - The Case | Renal dysfunction in a pregnant patient with IgA nephropathy.

PMID- 24875564
TI  - Adipose tissue and liver metabolic responses to different levels of dietary
      carbohydrates in gilthead sea bream (Sparus aurata).
AB  - This study analyzes the effects of replacing dietary lipids by carbohydrates and
      carbohydrates by fiber on gilthead sea bream growth, as well as lipid and glucose
      metabolism in adipose tissue and liver over the course of a 15-week feeding
      trial. Six different diets were formulated and fish were classified into two
      experimental groups sharing one diet. In the first group (LS), fish were fed four
      diets where lipids were reduced (23%-17%) by increasing carbohydrates (12%-28%)
      and, the second group (SF) consisted on three diets where the amount of
      carbohydrates (28%-11%) was exchanged at expenses of fiber (1%-18%). Differences
      in growth were not observed; nevertheless, the hepatosomatic index was positively
      related to dietary starch levels, apparently not due to enhanced hepatic
      lipogenesis, partly supported by unchanged G6PDH expression. In the LS group,
      lipogenic activity of adipose tissue was stimulated with low-lipid/high
      carbohydrate diets by up-regulating G6PDH expression and a tendency to increase
      FAS, and promoted carbohydrate utilization versus fatty acid oxidation by
      modulating the transcription factors LXRalpha, PPARalpha and PPARbeta expression.
      In the SF group, PPARs and LXRalpha increased parallel to fiber levels in adipose
      tissue. Furthermore, an adaptation of hepatic GK to dietary starch inclusion was
      observed in both groups; however, the lack of effects on G6Pase expression
      indicated that gluconeogenesis was not nutritionally regulated under the
      conditions examined. Overall, metabolic adaptations directed to an efficient use
      of dietary carbohydrates are present in gilthead sea bream, supporting the
      possibility of increasing carbohydrate or fiber content in diets for aquaculture
      sustainability. 

PMID- 24875566
TI  - Molecular responses of fishes to elevated carbon dioxide.
AB  - Hypercarbia, or elevated carbon dioxide, is an environmental challenge that can
      have detrimental effects on the physiology and performance of aquatic organisms.
      With aquatic hypercarbia predicted to become more prevalent in the future due to
      global climate change, it is important to quantify how hypercarbia impacts
      aquatic organisms, especially fish. The impact of hypercarbia on the behavior and
      physiology of fishes has been well studied, but relatively few studies have
      examined the molecular processes that underlie resulting behavioral and
      physiological changes. In an effort to define the molecular response of fishes to
      acute hypercarbia exposure, bluegill (Lepomis macrochirus) and silver carp
      (Hypophthalmichthys molitrix) were exposed to either 30 mg L(-1) CO2 (pCO2~15,700
      MUatm) or ambient (10 mg L(-1) CO2; pCO2~920 MUatm) conditions for 1h and the
      expression of a variety of genes, across three tissues, were compared. Exposure
      to 30 mg L(-1) CO2 in bluegill and silver carp resulted in an increase in c-fos,
      hif1-alpha, and gr-2 transcripts, while silver carp alone showed increases in
      hsp70 and hsc70-2 mRNA. This study demonstrates that acute hypercarbia exposure
      impacts gene expression in a species and tissue specific manner, which can be
      useful in identifying potential mechanisms for hypercarbia tolerance between
      species, and pinpoint specific tissues that are sensitive to hypercarbia
      exposure.

PMID- 24875565
TI  - The effects of exogenous cortisol on myostatin transcription in rainbow trout,
      Oncorhynchus mykiss.
AB  - Glucocorticoids (GCs) strongly regulate myostatin expression in mammals via
      glucocorticoid response elements (GREs), and bioinformatics methods suggest that
      this regulatory mechanism is conserved among many vertebrates. However, the
      multiple myostatin genes found in some fishes may be an exception. In silico
      promoter analyses of the three putative rainbow trout (Oncorhynchus mykiss)
      myostatin promoters have failed to identify putative GREs, suggesting a
      divergence in myostatin function. Therefore, we hypothesized that myostatin mRNA
      expression is not regulated by glucocorticoids in rainbow trout. In this study,
      both juvenile rainbow trout and primary trout myoblasts were treated with
      cortisol to examine the effects on myostatin mRNA expression. Results suggest
      that exogenous cortisol does not regulate myostatin-1a and -1b expression in
      vivo, as myostatin mRNA levels were not significantly affected by cortisol
      treatment in either red or white muscle tissue. In red muscle, myostatin-2a
      levels were significantly elevated in the cortisol treatment group relative to
      the control, but not the vehicle control, at both 12 h and 24 h post-injection.
      As such, it is unclear if cortisol was acting alone or in combination with the
      vehicle. Cortisol increased myostatin-1b expression in a dose-dependent manner in
      vitro. Further work is needed to determine if this response is the direct result
      of cortisol acting on the myostatin-1b promoter or through an alternative
      mechanism. These results suggest that regulation of myostatin by cortisol may not
      be as highly conserved as previously thought and support previous work that
      describes potential functional divergence of the multiple myostatin genes in
      fishes.

PMID- 24875567
TI  - [Multiple sclerosis and pelviperineology: Urinary and sexual dysfunctions and
      pregnancy].
AB  - GOAL: The aim was to review the literature on genito-urinary dysfunction in
      multiple sclerosis (MS). MATERIAL: A literature review through the PubMed library
      until August, 31 2013 was carried out using the following keywords: multiple
      sclerosis and neurogenic bladder, neuropathic bladder, bladder, management,
      follow-up, urological complications, urological treatment, sexual dysfunction,
      female sexual function, male sexual function, erectile dysfunction, anorectal,
      faecal, constipation, bowel, pregnancy, parturition, delivery, breast-feeding.
      RESULTS: Genito-urinary dysfunction is frequent in MS (35-90%) and may happen
      soon in the disease. Urinary symptoms (10-90%) are manifold resulting in a
      quality of life alteration and the onset of complications in 30% of the cases
      requiring a long-term follow-up. Sexual dysfunctions (35-87%) are also manifold
      affecting all the sexuality domains in men and women. Except the
      phosphodiesterase V inhibitors, few treatments have been assessed in this
      population. Pregnancy is nowadays considered as beneficial resulting in a disease
      slow-down and the lack of disease worsening despite an increase in disease
      relapse during the post-partum first quarter. It seems to be better to consider
      getting pregnant after at least one year without any relapse and to emphasize an
      exclusive breast-feeding. CONCLUSION: Urinary and sexual dysfunctions are
      frequent in MS. A transdisciplinary approach including the neurologist and
      pelviperineology specialists facilitates a disability adapted early management.

PMID- 24875568
TI  - [Clinical and paraclinical evaluations of bladder sensitivity. Review of the
      literature].
AB  - INTRODUCTION: The aim of this work was to carry out a review of the literature on
      the clinical and paraclinical evaluation of bladder sensory (BS) to better
      understand BS disorders in nonneurological patients. METHODS: Thirty-three
      articles were selected from the Medline((r)) Database between 1992 and 2012 using
      the following key words: "sensory/sensitivity bladder evaluation",
      "sensory/sensitivity bladder scale", "sensory/sensitivity bladder questionnaire",
      "urodynamic bladder sensory", "urgency questionnaire" and "Overactive Bladder
      (OAB) questionnaire". RESULTS: Evaluation of BS by asking questions during
      cystometry is validated (LE 2). The sensation of the desire to void progresses
      linearly with bladder filling (LE 2). Many symptoms and quality of life
      questionnaires related to BS anomalies have been proposed. Bladder diaries,
      frequency/volume curves (LE 2) and clinical algorithms (LE 3) could be an
      alternative to evaluate BS. CONCLUSION: Current evaluation only provides a
      partial view of BS. A multidimensional approach should lead to better
      understanding of BS disorders.

PMID- 24875569
TI  - [Efficacy of periurethral injections of polyacrylamide hydrogel (Bulkamid((r)))
      and quality of life of patients with urinary incontinence due to sphincter
      deficiency (IUE-IS)].
AB  - INTRODUCTION: This study was carried out to evaluate the efficacy of periurethral
      injection of polyacrylamide hydrogel (PAHG, Bulkamid((r)), Ethicon) for the
      treatment of female stress urinary incontinence (SUI). METHODS: Single-center
      prospective study: periurethral injection of Bulkamid((r)) was performed in 80
      patients with severe urinary incontinence between June 2010 and October 2011. The
      evaluation of the impact on quality of life was carried out using the Patient
      Global Impression of Severity (PGI-S), the International Consultation on
      Incontinence Questionnaire - Short Form (ICIQ-SF) and Patient Global Impression
      of Improvement (PGI-I) before and after treatment. RESULTS: With a mean follow-up
      of 18.6 +/- 5.3 months, 60% of patients had improved. For 30/74 (40%) there was
      no improvement and no patient had worsening of PGI-I after injection. Before
      surgery, 55.4% of patients considered their condition as severe (PGI-S). After
      injecting 21/74 (28%) and 11/74 (15%) considered it normal and severe (zero
      leakage). The ICIQ -SF score increased from 17 +/- 2.84 before injection to 13 +/
      5.52 after surgery, with a significant 30% decrease (P<0.00001). The reinjection
      rate was 29%. The complication rate was 16% (17/108): 11 cases of transient
      postoperative retention, 2 cases of cystitis, dysuria four episodes. No abscess
      or infection at the injection site, no specific complication to the product used.
      CONCLUSION: With an (PGI-I) improvement rate of 60 and 15% of patients without
      leakage (PGI-S/ICIQ), periurethral injection of Bulkamid((r)) is an effective and
      safe treatment option for women with a severe urinary incontinence especially in
      therapeutic failure. LEVEL OF PROOF: 4.

PMID- 24875570
TI  - [Functional symptoms and associations of women with genital prolapse].
AB  - OBJECTIVE: To assess functional symptoms related to genital prolapse and to test
      anatomo-functional associations. PATIENTS AND METHODS: Observational study,
      performed between January 2005 and June 2012, on all patients operated for
      prolapse in a French tertiary referral centre. Data were collected from
      standardized patients' notes, including baseline characteristics, complete
      interview on urinary and colo-rectal functional symptoms, MHU score, and POP-Q
      (Pelvic Organ Prolapse Quantification) clinical evaluation. RESULTS: Three
      hundred and seventy-four patients, with a mean age of 65.1 years old, mean parity
      of 2.5, and mean BMI of 25.4, were included. These patients were post-menopausal
      in 92.5% of cases. Urinary symptoms were: SUI in 30.5%, urgencies in 44.4%, and
      voiding difficulties in 38.8%. Colo-rectal symptoms, such as defecatory
      dysfunction and anal incontinence, occurred in 25.1% and 18.5%, respectively. On
      clinical examination, anterior vaginal wall prolapses were the most common
      (74.1%). Patients with stage 3-4 cystocele suffered significantly more frequently
      of nocturia (P=0.04), voiding difficulties (P=0.04), and occult stress urinary
      incontinence (P<0.001). Patients with stage 3-4 rectocele suffered significantly
      more frequently of defecatory dysfunction (P=0.005) and performed more often
      maneuver for defecation (P<0.001). CONCLUSION: Urinary and colo-rectal symptoms
      are commonly associated with genital prolapse. Anatomo-functional associations
      were shown regarding different prolapse types and stages. LEVEL OF PROOF: 4.

PMID- 24875571
TI  - [Transvaginal repair of genital prolapse using a light-weight mesh by the vaginal
      route].
AB  - OBJECTIVE: To evaluate the results associated with the transvaginal repair of
      genital prolapse using a tension free light-weight polypropylene mesh. PATIENTS
      AND METHODS: One hundred and fifteen patients have been treated in a single
      centre. Pre-operative and operative data and complications were recorded.
      Patients were examined at 1, 6 and 12 months. Anatomical failure was defined as
      follows: Pelvic Organ Prolapse Quantification (POP-Q) stage II or more. RESULTS:
      Seventy-seven (67%) patients completed 6 months follow-up and 45 (39%) patients
      completed 12 months follow-up. Finally, 70 (61%) patients were lost to follow-up,
      including 2 deaths (not related to surgery). Mean age was 66 years. All patients
      were treated with an anterior and apical and 20 patients were additionally
      treated with a posterior mesh. Among the 77 patients who completed 6 months
      follow-up, the complications reported were: 2 (2%) bladder injuries, 1 (1%)
      hematoma, 1 (1%) bleeding>200 mL and 1 (1%) vaginal mesh exposure. At one year, 6
      (7%) patients suffered from urinary stress incontinence, 5 (4%) suffered from
      urgency and 4 (5%) had dyspareunia. Among the 45 patients who completed 12 months
      follow-up, functional success was 95% and anatomical success was 77%. CONCLUSION:
      In this series, the placement of a light-weight transvaginal polypropylene mesh
      was associated with good functional results and a moderate prevalence of
      complications. LEVEL OF EVIDENCE: 4.

PMID- 24875573
TI  - [Cervical carcinoma and complete genital prolapse].

PMID- 24875572
TI  - [Epidemiology, etiology and psychosocial impact of urogenital fistulas in a
      cohort of 170 consecutive patients managed in three treatment centers in Burkina
      Faso from 2010 to 2012].
AB  - OBJECTIVE: To describe the socio-demographical aspects, etiologies and
      psychosocial consequences of urogenital fistula patients (UGF) in Burkina Faso
      (BF). PATIENTS AND METHODS: Descriptive study of a cohort of consecutive patients
      during a period of 18 months (December 1st 2010 to August 31st 2012) in three
      centers of treatment in BF. Each patient has had a standardized complete medical
      observation focused on sociodemographics, clinical finding, past medical history
      and etiologies of UGF. Some patients had an interview with a psychologist.
      RESULTS: One hundred and seventy patients with mean age 35 years (minimum: 16,
      maximum: 70) were enrolled during the study period. The majority of patients were
      housewives (90.5%, n=152) and illiterates (92.9%, n=158). Among the patients,
      62.4% (n=106) lived in rural zones. Obstetrical fistula was the most common cause
      of UGF (87.6%, n=149) in our study and prolonged labor occurred in 93.3% (n=139)
      of cases with 17.5% (n=26) who delivered at home. The majority of our cases were
      vesico-vaginal fistula (70.6%, n=120). Fifty-five patients (32.4%) were divorced
      after the fistula. The sensation of humiliation and sadness were noted at all the
      patients who had a psychological evaluation and 87.5% (n=14) of them have had
      suicidal ideas. CONCLUSION: The UGF are frequent in Burkina Faso and obstetrical
      etiology is dominant. The physical and psychosocial repercussions are important
      for the women victims of this pathology. LEVEL OF EVIDENCE: 4.

PMID- 24875576
TI  - Carbon nanotube terahertz detector.
AB  - Terahertz (THz) technologies are promising for diverse areas such as medicine,
      bioengineering, astronomy, environmental monitoring, and communications. However,
      despite decades of worldwide efforts, the THz region of the electromagnetic
      spectrum still continues to be elusive for solid state technology. Here, we
      report on the development of a powerless, compact, broadband, flexible, large
      area, and polarization-sensitive carbon nanotube THz detector that works at room
      temperature. The detector is sensitive throughout the entire range of the THz
      technology gap, with responsivities as high as ~2.5 V/W and polarization ratios
      as high as ~5:1. Complete thermoelectric and opto-thermal characterization
      together unambiguously reveal the photothermoelectric origin of the THz
      photosignal, triggered by plasmonic absorption and collective antenna effects,
      and suggest that judicious design of thermal management and quantum engineering
      of Seebeck coefficients will lead to further enhancement of device performance.

PMID- 24875574
TI  - The juvenile myoclonic epilepsy mutant of the calcium channel beta(4) subunit
      displays normal nuclear targeting in nerve and muscle cells.
AB  - Voltage-gated calcium channels regulate gene expression by controlling calcium
      entry through the plasma membrane and by direct interactions of channel fragments
      and auxiliary beta subunits with promoters and the epigenetic machinery in the
      nucleus. Mutations of the calcium channel beta(4) subunit gene (CACNB4) cause
      juvenile myoclonic epilepsy in humans and ataxia and epileptic seizures in mice.
      Recently a model has been proposed according to which failed nuclear
      translocation of the truncated beta(4) subunit R482X mutation resulted in altered
      transcriptional regulation and consequently in neurological disease. Here we
      examined the nuclear targeting properties of the truncated beta(4b(1-481))
      subunit in tsA-201 cells, skeletal myotubes, and in hippocampal neurons. Contrary
      to expectation, nuclear targeting of beta(4b(1-481)) was not reduced compared
      with full-length beta(4b) in any one of the three cell systems. These findings
      oppose an essential role of the beta(4) distal C-terminus in nuclear targeting
      and challenge the idea that the nuclear function of calcium channel beta(4)
      subunits is critically involved in the etiology of epilepsy and ataxia in
      patients and mouse models with mutations in the CACNB4 gene.

PMID- 24875577
TI  - F-18 FDG PET/CT in the evaluation of Takayasu arteritis: an experience from the
      tropics.
AB  - OBJECTIVE: To evaluate the performance parameters of FDG PET/CT in patients with
      Takayasu arteritis at diagnosis and during immunosuppression. METHODS:
      Retrospective analysis of 60 FDG PET/CT studies in 51 patients was performed (17
      scans at diagnosis out of which 4 had follow-up scans also and 43 scans on
      immunosuppression). The degree of FDG uptake in the vessels was assessed visually
      using a 4-point scale and maximum standardized uptake value (SUVmax), SUVratio,
      extent of vasculitis and association with ESR were calculated. RESULTS: PET/CT
      was positive for active vasculitis in all 17 patients at diagnosis. The mean
      SUVmax and mean SUV ratio of the active areas were 5.1 +/- 3.0 and 3.2 +/- 1.9,
      respectively. On immunosuppression, PET scan was positive for active vasculitis
      in 14/43 (32.5%) scans. The mean SUVmax and mean SUVratio of the active areas
      were 1.7 +/- 2.1 and 0.95 +/- 1.2, respectively. There was significant difference
      between the mean SUVmax and mean SUVratio at diagnosis and on immunosuppression,
      respectively (P < .01). The median number of vascular segments in each uptake
      grade group was also statistically different (P < .01) between scans at diagnosis
      and on immunosuppression. The median ESR level in PET positive scans was 29
      mm/hour (2-53), whereas in PET negative scans was 35.5 mm/hour (6-50) and the
      difference was not statistically significant. CONCLUSION: FDG PET/CT showed good
      sensitivity to detect active vasculitis at diagnosis and during
      immunosuppression. The change in SUVmax between the successive FDG PET/CT scans
      may give an objective assessment of response to immunosuppression.

PMID- 24875578
TI  - Preclinical characterization of a novel radiolabeled analog of practolol for the
      molecular imaging of myocardial beta-adrenoceptor density.
AB  - BACKGROUND: The great clinical potential of myocardial beta-AR imaging has been
      shown by recent studies evaluating the beta-AR-specific, non-selective agent
      [(11)C]-CGP12177 in the setting of idiopathic-dilated cardiomyopathy, and
      myocardial infarction. However, the short half-life of (11)C hampers the
      potential of [(11)C]-CGP12177 for routine clinical use. AMI9 is an analog of the
      beta-adrenoceptor ligand practolol that can readily be labeled using radioactive
      isotopes of iodine. The present study was aimed at characterizing the in vitro,
      ex vivo, and in vivo beta-AR binding properties of [(125)I]-AMI9. METHODS AND
      RESULTS: Newborn rat cardiomyocytes were used for saturation and kinetic binding
      assays as well as for displacement and competition experiments. Isolated perfused
      rat hearts were used to evaluate the pharmacological activity of AMI9. The in
      vivo kinetics of [(125)I]-AMI9 were studied using biodistribution experiments in
      mice. [1(25)I]-AMI9 displayed high specific affinity for beta-AR with no beta-AR
      subtype selectivity (K D, 5.6 +/- 0.3 nM; B max, 231 +/- 7 fmol.(mg protein)(
      1)). AMI9 potently inhibited the inotropic effects of isoproterenol. The early in
      vivo cardiac and lung activities of [(125)I]-AMI9 compared favorably with those
      of the clinically validated tracer CGP12177. CONCLUSION: Iodine-labeled AMI9 is a
      promising agent for the molecular imaging of myocardial beta-AR density.

PMID- 24875579
TI  - Is TOMPOOL (gated blood-pool SPECT processing software) accurate to diagnose
      right and left ventricular dysfunction in a clinical setting?
AB  - BACKGROUND: The assessment of right ventricular function is crucial for
      management of heart disease. TOMPOOL is a software that processes data acquired
      with Tomographic Equilibrium Radionuclide Ventriculography. In this report,
      TOMPOOL's diagnostic accuracy and inter-observer reproducibility were assessed in
      a cohort of patients with various etiologies of ventricular dysfunction. METHODS
      AND RESULTS: End-diastolic volume (EDV), ejection fraction (EF), and cardiac
      output (CO) were calculated for the right ventricle (RV) and the left ventricle
      (LV) using TOMPOOL in 99 consecutive patients. Thirty-five patients underwent
      cardiac magnetic resonance imaging (CMR) considered as the reference-standard to
      measure EDV and EF; the Spearman's rho correlation coefficients were r =
      0.73/0.80 and 0.67/0.73 for right/left EF and EDV, respectively. Twenty-one
      patients had thermodilution measurements of right CO (reference-standard), the
      correlation was r = 0.57. The best cut-off points (sensitivity/specificity) in
      order to diagnose a ventricular dysfunction or enlargement were 46% for RVEF
      (67%/89%), 62% for LVEF (100%/90%), 94 mL for RVEDV (77%/73%), and 84 mL for
      LVEDV (100%/91%). The areas under the ROC curve were, respectively, 0.79, 0.91,
      0.83, and 0.99. Inter-observer reproducibility was r = 0.81/0.94, 0.77/0.90, and
      0.78/0.75 for Right/Left EF, EDV, and CO, respectively. CONCLUSION: TOMPOOL is
      accurate: measurements of EDV, EF, and CO are reproducible and correlate with CMR
      and thermodilution. However, thresholds must be adjusted.

PMID- 24875581
TI  - Threonine requirement of White Pekin ducks from hatch to 21 d of age.
AB  - 1. A dose-response experiment with 5 dietary threonine concentrations (5.0, 5.8,
      6.6, 7.4 and 8.2 g/kg) was conducted to estimate the threonine requirement of
      White Pekin ducks from hatch to 21 d of age. 2. A total of 240 one-d-old male
      White Pekin ducks were allotted to 5 experimental treatments and each treatment
      contained 6 replicate pens with 8 ducks per pen. Ducks were reared in raised wire
      floor pens from hatch to 21 d of age. At 21 d of age, growth performance and
      intestinal morphology were determined. 3. The weight gain and feed intake of
      Pekin ducks increased and feed/gain of these birds decreased linearly or
      quadratically as dietary threonine increased from 5.0 to 8.2 g threonine/kg.
      Compared to ducks fed on diets containing 5.0 g threonine/kg, ducks given diets
      containing 7.4 g threonine/kg had higher villus height in duodenum, jejunum and
      ileum. 4. The threonine requirements for weight gain of White Pekin ducks from
      hatch to 21 d of age was estimated to be 6.72 g/kg when dietary crude protein
      concentration was 189.8 g/kg and threonine supply was critical for maintaining
      intestinal structure of these birds.

PMID- 24875582
TI  - Concurrent validity of approximate number sense tasks in adults and children.
AB  - Reasoning with non-symbolic numerosities is suggested to be rooted in the
      Approximate Number System (ANS) and evidence pointing to a relationship between
      the acuity of this system and mathematics is available. In order to use the
      acuity of this ANS as a screening instrument to detect future math problems, it
      is important to model ANS acuity over development. However, whether ANS acuity
      and its development have been described accurately can be questioned. Namely,
      different tasks were used to examine the developmental trajectory of ANS acuity
      and studies comparing performances on these different tasks are scarce. In the
      present study, we examined whether different tasks designed to measure the acuity
      of the ANS are comparable and lead to related ANS acuity measures (i.e., the
      concurrent validity of these tasks). We contrasted the change detection task,
      which is used in infants, with tasks that are more commonly used in older
      children and adults (i.e., comparison and same-different tasks). Together, our
      results suggest that ANS acuity measures obtained with different tasks are not
      related. This poses serious problems for the comparison of ANS acuity measures
      derived from different tasks and thus for the establishment of the developmental
      trajectory of ANS acuity. 

PMID- 24875583
TI  - Flexible metal-organic frameworks.
AB  - Advances in flexible and functional metal-organic frameworks (MOFs), also called
      soft porous crystals, are reviewed by covering the literature of the five years
      period 2009-2013 with reference to the early pertinent work since the late 1990s.
      Flexible MOFs combine the crystalline order of the underlying coordination
      network with cooperative structural transformability. These materials can respond
      to physical and chemical stimuli of various kinds in a tunable fashion by
      molecular design, which does not exist for other known solid-state materials.
      Among the fascinating properties are so-called breathing and swelling phenomena
      as a function of host-guest interactions. Phase transitions are triggered by
      guest adsorption/desorption, photochemical, thermal, and mechanical stimuli.
      Other important flexible properties of MOFs, such as linker rotation and sub-net
      sliding, which are not necessarily accompanied by crystallographic phase
      transitions, are briefly mentioned as well. Emphasis is given on reviewing the
      recent progress in application of in situ characterization techniques and the
      results of theoretical approaches to characterize and understand the breathing
      mechanisms and phase transitions. The flexible MOF systems, which are discussed,
      are categorized by the type of metal-nodes involved and how their coordination
      chemistry with the linker molecules controls the framework dynamics. Aspects of
      tailoring the flexible and responsive properties by the mixed component solid
      solution concept are included, and as well examples of possible applications of
      flexible metal-organic frameworks for separation, catalysis, sensing, and
      biomedicine. 

PMID- 24875580
TI  - A multilevel analysis of gender, Latino immigrant enclaves, and tobacco use
      behavior.
AB  - Research suggests that immigrant enclaves positively influence health behaviors
      such as tobacco use through supportive social networks and informal social
      control mechanisms that promote healthy behavioral norms. Yet, the influence of
      social cohesion and control on tobacco use may depend on smoking-related norms,
      which can vary by gender. This study examines the influence of neighborhood
      Latino immigrant enclave status on smoking and cessation among Hispanic men and
      women. Data from the Los Angeles Family and Neighborhood Survey was combined with
      census data to assess the relationship between immigrant enclaves, gender, and
      smoking using multilevel regression. The effect of the Hispanic enclave
      environment on smoking differed by gender. Living in an enclave had a harmful
      effect on tobacco use among Hispanic men, marginally increasing the likelihood of
      smoking and significantly reducing cessation. This effect was independent of
      neighborhood socioeconomic status, nativity, and other individual demographics.
      Neighborhood immigrant concentration was not associated with smoking or cessation
      for Hispanic women. Research, interventions, and policies aimed at reducing
      smoking among Hispanics may need to be gender responsive to ensure effectiveness
      as well as health and gender equity. 

PMID- 24875584
TI  - Extremely efficient liquid exfoliation and dispersion of layered materials by
      unusual acoustic cavitation.
AB  - Layered materials must be exfoliated and dispersed in solvents for diverse
      applications. Usually, highly energetic probe sonication may be considered to be
      an unfavourable method for the less defective exfoliation and dispersion of
      layered materials. Here we show that judicious use of ultrasonic cavitation can
      produce exfoliated transition metal dichalcogenide nanosheets extraordinarily
      dispersed in non-toxic solvent by minimising the sonolysis of solvent molecules.
      Our method can also lead to produce less defective, large graphene oxide
      nanosheets from graphite oxide in a short time (within 10 min), which show high
      electrical conductivity (>20,000 S m(-1)) of the printed film. This was achieved
      by adjusting the ultrasonic probe depth to the liquid surface to generate less
      energetic cavitation (delivered power ~6 W), while maintaining sufficient
      acoustic shearing (0.73 m s(-1)) and generating additional microbubbling by
      aeration at the liquid surface.

PMID- 24875585
TI  - Granzyme B gene polymorphism associated with subacute sclerosing panencephalitis.
AB  - BACKGROUND:  Subacute sclerosing panencephalitis (SSPE) is a late complication of
      measles infection. Immune dysfunction related to genetic susceptibility has been
      considered in disease pathogenesis. A functional single nucleotide polymorphism
      (SNP) of granzyme B gene (GZMB) reported in several pathologies may also be
      involved in susceptibility to SSPE. PATIENTS AND METHODS:  An SNP (rs8192917, G 
      > A, R->Q) was screened in 118 SSPE patients and 221 healthy controls (HC) by
      polymerase chain reaction-restriction fragment length polymorphism. Frequencies
      were compared between groups. In vitro production of GZMB was measured in
      controls with different genotypes. RESULTS:  The SNP had a minor allele (G)
      frequency of 0.22 in patients and 0.31 in controls. GG genotype was significantly
      less frequent in patients (odds ratio, 0.23). G allele carriers produced
      relatively higher levels of GZMB, when stimulated in vitro. CONCLUSION:  These
      findings implicate possible effect of this genetic polymorphism in susceptibility
      to SSPE which needs to be confirmed in bigger populations.

PMID- 24875586
TI  - Melittin modifies bending elasticity in an unexpected way.
AB  - Understanding the molecular mechanism of the interaction of amphipathic and
      antimicrobial peptides with membranes is of fundamental interest, especially
      because of the potential of amphipathic peptides as therapeutics. The most
      studied amphipathic peptides in this context are certainly melittin, magainin and
      alamethicin, of which melittin is the only one to exhibit a powerful hemolytic
      and therefore toxic action. Herein we study the effect of the antimicrobial but
      hemolytic peptide melittin on the bending elasticity of giant unilamellar
      vesicles (GUVs). The results are compared to the effects of non-hemolytic
      amphipathic peptides such as alamethicin. We found that monomeric melittin acts
      very differently on the membrane mechanical properties. Strikingly, the
      difference is the most pronounced for low peptide concentrations, relevant for
      the hemolytic action. This gives some insight into the subtle nature of this
      peptide-membrane interaction. Furthermore, the results show that bending
      elasticity measurements might be a sensitive way to distinguish between lytic and
      non-lytic antimicrobial peptides. 

PMID- 24875587
TI  - Engraftment of mouse amniotic fluid-derived progenitor cells after in utero
      transplantation in mice.
AB  - BACKGROUND/PURPOSE: Amniotic fluid-derived progenitor cells (AFPCs) are
      oligopotent and shed from the fetus into the amniotic fluid. It was reported that
      AFPCs express stem cell-like markers and are capable of differentiating into
      specific cell type in in vitro experiments. However, no study has fully
      investigated the potentiality and destiny of these cells in in vivo experiments.
      METHODS: Ds-red transgenic mice (on Day 13.5 of pregnancy) were transplanted in
      utero with enhanced green fluorescent protein-labeled mouse AFPC (EGFP-mAFPCs).
      After birth, baby mice were euthanized at 3-week intervals beginning 3 weeks
      postnatally, and the specimens were examined by polymerase chain reaction,
      histology, and flow cytometry. RESULTS: Our results demonstrate the
      transplantability of mAFPCs into all three germ layers and the potential of
      mAFPCs in the study of progenitor cell homing, differentiation, and function.
      Engraftment of EGFP-mAFPCs was detected in the intestine, kidney, muscle, skin,
      bladder, heart, stomach, etc., at 3 weeks after delivery. CONCLUSION: This model
      using EGFP-mAFPCs injected in utero may provide an ideal method for determining
      the fate of transplanted cells in recipients and these findings may justify a
      clinical trial of in utero transplantation during gestation for patients who have
      inherited genetic disorders.

PMID- 24875588
TI  - Errors in science: the role of reviewers.
AB  - Reviewers play a key role in science, although studies suggest the current peer
      reviewing system has faults. We propose to introduce a quality control system to
      evaluate each journal's review process, and produce a Review Quality Index. We
      propose four schemes that have the potential to reduce errors in a key step in
      scientific decision making: the reviewing process. 

PMID- 24875589
TI  - Fine-grain modeling of species' response to climate change: holdouts, stepping
      stones, and microrefugia.
AB  - Microclimates have played a critical role in past species range shifts,
      suggesting that they could be important in biological response to future change.
      Terms are needed to discuss these future effects. We propose that populations
      occupying microclimates be referred to as holdouts, stepping stones and
      microrefugia. A holdout is a population that persists in a microclimate for a
      limited period of time under deteriorating climatic conditions. Stepping stones
      successively occupy microclimates in a way that facilitates species' range
      shifts. Microrefugia refer to populations that persist in microclimates through a
      period of unfavorable climate. Because climate projections show that return to
      present climate is highly unlikely, conservation strategies need to be built
      around holdouts and stepping stones, rather than low-probability microrefugia.

PMID- 24875591
TI  - Construction of rotacatenanes using rotaxane and catenane frameworks.
AB  - The construction of novel mechanically interlocked structures has become a topic
      of great current interest due to the requirements of topology and their potential
      application in molecular machines and devices. Rotaxane and catenane as two basic
      topological frameworks can be used to construct the fused structures. In the
      current investigation, a class of novel ammonium backbones were synthesized. The
      ammonium group incorporated in the linear part of the molecule can be used for
      templating rotaxane formation while the macrocyclic part of the molecule can be
      used for templating catenane formation. Accordingly, they were subjected to
      dynamic covalent chemistry, resulting in a series of [n]rota[n]catenane
      structures (n = 2, 3, 4). In this process, the N-hetero crown ethers were
      installed on ammonium template sites of linear and macrocyclic components all at
      once by a template-directed clipping reaction. The results showed that these
      novel building blocks could be assembled with high efficiencies. Finally, this
      investigation provides a foundation for future studies aimed at constructing
      complicated integrated structures or polymers with multiple topological units. 

PMID- 24875590
TI  - A prognostic model of therapy-related myelodysplastic syndrome for predicting
      survival and transformation to acute myeloid leukemia.
AB  - INTRODUCTION/BACKGROUND: We evaluated the characteristics of a cohort of patients
      with myelodysplastic syndrome (MDS) related to therapy (t-MDS) to create a
      prognostic model. PATIENTS AND METHODS: We identified 281 patients with MDS who
      had received previous chemotherapy and/or radiotherapy for previous malignancy.
      Potential prognostic factors were determined using univariate and multivariate
      analyses. RESULTS: Multivariate Cox regression analysis identified 7 factors that
      independently predicted short survival in t-MDS: age >= 65 years (hazard ratio
      [HR], 1.63), Eastern Cooperative Oncology Group performance status 2-4 (HR,
      1.86), poor cytogenetics (-7 and/or complex; HR, 2.47), World Health Organization
      MDS subtype (RARs or RAEB-1/2; HR, 1.92), hemoglobin (< 11 g/dL; HR, 2.24),
      platelets (< 50 * 10(9)/dL; HR, 2.01), and transfusion dependency (HR, 1.59).
      These risk factors were used to create a prognostic model that segregated
      patients into 3 groups with distinct median overall survival: good (0-2 risk
      factors; 34 months), intermediate (3-4 risk factors; 12 months), and poor (5-7
      risk factors; 5 months) (P < .001) and 1-year leukemia-free survival (96%, 84%,
      and 72%, respectively, P = .003). This model also identified distinct survival
      groups according to t-MDS therapy. CONCLUSION: In summary, we devised a
      prognostic model specifically for patients with t-MDS that predicted overall
      survival and leukemia-free survival. This model might facilitate the development
      of risk-adapted therapeutic strategies.

PMID- 24875593
TI  - Reciprocal influences between negative life events and callous-unemotional
      traits.
AB  - Children with conduct problems and co-occurring callous-unemotional (CU) traits
      show more severe, stable, and aggressive antisocial behaviors than those without
      CU traits. Exposure to negative life events has been identified as an important
      contributing factor to the expression of CU traits across time, although the
      directionality of this effect has remained unknown due to a lack of longitudinal
      study. The present longitudinal study examined potential bidirectional effects of
      CU traits leading to experiencing more negative life events and negative life
      events leading to increases in CU traits across 3 years among a sample of
      community-based school-aged (M = 10.9, SD = 1.71 years) boys and girls (N = 98).
      Repeated rating measures of CU traits, negative life events and conduct problems
      completed by children and parents during annual assessments were moderately to
      highly stable across time. Cross-lagged models supported a reciprocal
      relationship of moderate magnitude between child-reported CU traits and
      "controllable" negative life events. Parent-reported CU traits predicted
      "uncontrollable" life events at the earlier time point and controllable life
      events at the later time point, but no reciprocal effect was evident. These
      findings have important implications for understanding developmental processes
      that contribute to the stability of CU traits in youth. 

PMID- 24875592
TI  - Immigration transition and depressive symptoms: four major ethnic groups of
      midlife women in the United States.
AB  - The purpose of this study was to explore the relationships between immigration
      transition and depressive symptoms among 1,054 midlife women in the United
      States. This was a secondary analysis of the data from two national Internet
      survey studies. Questions on background characteristics and immigration
      transition and the Depression Index for Midlife Women were used to collect the
      data. The data were analyzed using inferential statistics including multiple
      regressions. Immigrants reported lower numbers of symptoms and less severe
      symptoms than nonimmigrants (p <.01). When controlling for background
      characteristics, self-reported racial/ethnic identity and immigration status were
      significant predictors of depressive symptoms (R(2) =.01, p <.05). 

PMID- 24875594
TI  - Factors affecting microbial spoilage and shelf-life of chilled vacuum-packed lamb
      transported to distant markets: a review.
AB  - Vacuum-packaging and stringent control of storage temperatures enable the export
      of meat to distant markets, supplying a chilled product that can favourably
      compete with local fresh meats. To save fuel and reduce emissions, the speed of
      ships travelling to international markets has decreased resulting in requirement
      for the shelf-life of chilled lamb to be extended beyond the recognised time of
      60-70 days. Growth of microorganisms and ability to cause spoilage of vacuum
      packed lamb are dependent on many factors, including the type and initial
      concentration of spoilage bacteria, meat pH, water activity, availability of
      substrates, oxygen availability and, most importantly, storage time and
      temperature of the packaged product. This paper reviews the existing knowledge of
      the spoilage bacteria affecting vacuum-packed lamb, discusses the impact of these
      bacteria on product quality, shelf-life and spoilage, and concludes that under
      specified conditions the shelf-life of chilled lamb can be extended to beyond 70
      days.

PMID- 24875595
TI  - VACTERL syndrome.

PMID- 24875596
TI  - [A giant staghorn calculus in the biliary tract].

PMID- 24875599
TI  - Localization of desmin in cultured astrocytes and its distribution in relation to
      glial fibrillary acidic (GFA) protein.
AB  - In dissociated cultures from newborn rat brain, it is shown that astrocytes which
      are positive with GFA antisera also stain with desmin antisera. However, the
      localization of these two proteins within the same cell seems to be different as
      revealed by double immunofluorescence employing both these antisera. 

PMID- 24875600
TI  - Role of ornithine decarboxylase and the polyamines in nervous system development:
      Short-term postnatal administration of alpha-difluoromethylornithine, an
      irreversible inhibitor of ornithine decarboxylase.
AB  - The role of ornithine decarboxylase (ODC) and the polyamines in development of
      central and peripheral catecholaminergic neurons was examined through the use of
      alpha-difluoromethylornithine (DFMO), a specific irreversible inhibitor of ODC.
      Short-term postnatal administration of DFMO (500 mg/kg daily on days 1-6) to
      neonatal rats resulted in effective inhibition of ODC and depletion of both
      putrescine and spermidine in brain, heart and kidney; after cessation of DFMO
      administration, polyamine levels returned to normal by 10-13 days of age. There
      were no signs of generalized toxicity of short-term DFMO treatment, as body
      weight gains were largely unaffected over the course of study (through weaning).
      However, development of peripheral sympathetic neurons was severely retarded by
      DFMO, with persistent and profound deficits of both cardiac and renal
      norepinephrine; the catecholamine deficiencies were unrelated to effects on end
      organ growth, as cardiac weights were essentially normal whereas kidney weights
      were adversely affected by DFMO. Development of the adrenal medulla, a peripheral
      catecholaminergic tissue which displays approximately the same developmental
      profile as do sympathetic neurons but which does not develop axonal projections,
      was not slowed by DFMO treatment; similarly, central noradrenergic and
      dopaminergic neurons, which undergo the majority of axonal outgrowth and
      synaptogenesis during the second to third postnatal week (just after the period
      in which polyamines returned to control levels), developed normally as assessed
      by measurements of transmitter levels, tyrosine hydroxylase activity and
      synaptosomal uptake of [(3)H]norepinephrine or [(3)H]dopamine. Extension of the
      period of DFMO treatment and consequent depletion of polyamines into the period
      in which central synaptogenesis occurs does, however, produce slowing of
      development of brain catecholamine neuronal projections. Thus, the ODC/polyamine
      system appears to play a critical postnatal role in catecholamine systems
      specifically undergoing active synaptogenesis. 

PMID- 24875597
TI  - Facile solid phase peptide synthesis with a Re-lysine conjugate generated via a
      one-pot procedure.
AB  - We have synthesized a Re(CO)3-modified lysine via a one-pot Schiff base formation
      reaction that can be used in the solid phase peptide synthesis. To demonstrate
      its potential use, we have attached it to a neurotensin fragment and observed
      uptake into human umbilical vascular endothelial cells. 

PMID- 24875598
TI  - Hypoxia-mediated retinal neovascularization and vascular leakage in diabetic
      retina is suppressed by HIF-1alpha destabilization by SH-1242 and SH-1280, novel
      hsp90 inhibitors.
AB  - In diabetic retinopathy (DR), visual deterioration is related with retinal
      neovascularization and vascular hyperpermeability. Anti-vascular endothelial
      growth factor (VEGF) agents are currently utilized to suppress retinal
      neovascularization and macular edema (ME); however, there are still concerns on
      the widespread use of them because VEGF is a trophic factor for neuronal and
      endothelial cells in the retina. As an alternative treatment strategy for DR, it
      is logical to address hypoxia-related molecules to treat DR because the retina is
      in relative hypoxia as DR progresses. In this study, we demonstrate that
      destabilization of hypoxia-inducible factor-1alpha (HIF-1alpha) by SH-1242 and SH
      1280, novel heat shock protein 90 (hsp90) inhibitors, leads to suppression of
      hypoxia-mediated retinal neovascularization and vascular leakage in diabetic
      retina. In vitro experiments showed that these inhibitors inhibited hypoxia
      induced upregulation of target genes of HIF-1alpha and further secretion of VEGF.
      Furthermore, these inhibitors effectively suppressed expression of target genes
      of HIF-1alpha including vegfa in the retina of oxygen-induced retinopathy (OIR)
      mice. Interestingly, despite hsp90 inhibition, these inhibitors do not induce
      definite toxicity at the level of gene expression, cellular viability, and
      histologic integrity. We suggest that SH-1242 and SH-1280 can be utilized in the
      treatment of DR, as an alternative treatment of direct VEGF inhibition. Key
      message: SH-1242 and SH-1280 are novel hsp90 inhibitors similar to deguelin. HIF
      1alpha destabilization by hsp90 inhibition leads to anti-angiogenic effects.
      Despite hsp90 inhibition, both inhibitors do not induce definite toxicity. HIF
      1alpha modulation can be a safer therapeutic option than direct VEGF inhibition.

PMID- 24875601
TI  - Binding and uptake of putative neurotransmitters in mutant mouse cerebellum and
      cerebellar reaggregat.
AB  - gamma-Amino butyric acid (GABA) appears to be the inhibitory transmitter of
      various cerebellar interneurons, while glutamate has been suggested as the
      excitatory transmitter of granule cells. In this study we have determined the
      developmental profile from day 2 to day 60 for the Na(a)-independent (presumably
      post-synaptic receptor) binding of [(3)H]GABA (Kd = 34 nM) and [(3)H]kainic acid,
      a glutamate analog (Kd = 53 nM. Both binding activities increase steadily to
      adult levels with kainic acid achieving this more rapidly. Cerebellar cells (7
      day) cultured as reaggregates for 14 days showed an increase in GABA binding and
      glutamate uptake compared to the starting tissue but did not achieve the levels
      seen in vivo, while kainic acid binding and GABA uptake remained low. Binding and
      uptake measurements were performed in neurological mutants. Agranular mutants,
      weaver, reeler and staggerer demonstrated as expected, marked decreases in total
      GABA binding and glutamate uptake into synaptosomes, and to a lesser extent GABA
      uptake. In addition total kainate binding was depressed. In comparison, Purkinje
      cell degeneration mutants showed only a small decrease in kainic acid binding.
      These results suggest that kainic acid binding does not identify the post
      synaptic glutamate receptor. 

PMID- 24875602
TI  - Synapse selection based on differences in synapse turnover.
AB  - Rat retinal neurons formed transient synapses with rat muscle cells in culture
      only during a discrete period in development, from the 20th day of embryonic
      development to the 7th neonatal day. In contrast, chick embryo spinal cord
      neurons formed synapses at all developmental stages tested, from the 2nd to the
      18th day of embryonic development. The percentage of cells from the spinal cord
      that formed synapses with muscle cells was maximum at 4 days of embryonic
      development and decreased thereafter. However, the number of synapses with muscle
      formed by cells from 8-day embryonic spinal cord did not decrease during 14 days
      of culture. Under identical conditions, all synapses formed between rat retinal
      neurons and muscle cells were terminated during 7 days of culture. These results
      show that differences in the rates of turnover of two populations of cholinergic
      synapses can result in the selective retention of one population of synapses and
      the loss of the other, and thereby alter the specificity of synaptic connections.

PMID- 24875603
TI  - Acute-phase alpha2-macroglobulin in csf during development of the fetal rat.
AB  - The concentration of acute phase alpha2-macroglobulin (APalpha2M) was measured in
      the cerebrospinal fluid (csf) and plasma of fetal (12-22 days gestation) and
      neonatal (0-10 days post partum) rats. APalpha2M was detectable in the fetus as
      early as samples could be obtained (12 days) and increased in both fluids to
      reach a peak near the time of birth (17 mg/100 ml in csf and 168 mg/100 ml in
      plasma). During the neonatal period APalpha2M concentration declined markedly in
      both fluids. The results are compared with values for albumin and alpha
      fetoprotein in fetal rats. It was concluded that maintenance of the csf:plasma
      ratios for the three proteins are incompatible with an explanation of passive
      diffusion from plasma to csf. Other mechanisms to explain the occurrence of high
      concentrations of plasma proteins in fetal csf are discussed. 

PMID- 24875604
TI  - Postnatal development of rat alpha- and beta-adrenergic receptors: A comparison
      between tissues.
AB  - The rates of development of rat kidney alpha- and beta-adrenoceptors were
      compared with those of heart and lung adrenoceptors in the same animals by direct
      binding studies using [(3)H]WB4101 (alpha1), [(3)H]yohimbine (alpha2) and
      [(125)I]HYP (beta). Kidney alpha1 and beta-adrenoceptors had reached adult
      concentrations 7 days after birth, while the alpha2-adrenoceptor concentration
      plateaued at 21 days. Lung beta-adrenoceptor concentration was stable initially,
      then increased rapidly to adult levels by 18 days. In contrast, heart alpha1-and
      beta-adrenoceptor concentrations were at mature levels at birth. In all tissues
      studied the increase in noradrenaline concentration was slower than the increases
      in adrenoceptor concentrations. 

PMID- 24875605
TI  - The adrenocortical response to stress from the pre-hatching period to the adult
      state in the pigeon: Thalamic participation.
AB  - The stress-induced adrenocortical response was kinetically evaluated for 100 min
      after ether vapor exposure in late embryos (30 h before hatching) and in 1, 2, 3
      and 6-wk-old squabs. An-adult-pattern of corticosterone profile was seen in
      intact 6-wk-old pigeons, i.e. a polyphasic increase of corticosterone including
      successive peaks at 12-15, 35, 60 and 90 min after stress application. In 1-wk
      old squabs, a small adrenocortical response to stress included only a single peak
      of corticosterone at 12-15 min. The early peak was found again, with the same
      magnitude, 2 wk after hatching but it was followed by two later and smaller peaks
      35 and 60 min after stress. The adult pattern was visible in 3-wk-old stressed
      pigeons, although the magnitude of the response was still smaller than in adult
      controls. A single, high peak of corticosterone occurred 12-15 min after stress
      application, without any later peak, in embryos and a similar monophasic response
      was seen in thalamic lesioned adult birds. Therefore, it can be suggested that
      the polyphasic reverberating adrenocortical response to stress depends upon
      relationships between the adrenocorticotrophic hypothalamus and the anterior
      mediodorsal thalamus. Such thalamic-hypothalamic interrelations appear to mature
      during the early post-hatching weeks. 

PMID- 24875606
TI  - Characterization of monoamine oxidase activity during early stages of quail
      embryogenesis.
AB  - Catecholamines and other biogenic amines may play a role in early embryogenesis
      in addition to functioning as neurotransmitters after neuronal differentiation.
      Regulation of amine levels is mediated by several different parameters including
      activity levels of degradative enzymes. Since monoamine oxidase (EC 1.4.3.4) is
      the primary degradative enzyme for these biogenic amines, we have begun to
      characterize MAO activity during quail embryogenesis. Our results demonstrate
      that MAO activity is present at all stages of development examined (stages 2-22)
      and that the MAO specific activity levels are highest during the earliest stages
      (stages 2-6). Two types of MAO activity similar to adult avian and mammalian MAO
      A and MAO-B have been demonstrated by differential clorgyline sensitivity of
      tryptamine deamination. In addition, SDS-PAGE of embryonic quail [(3)H]pargyiine
      labeled MAO demonstrates that the quail MAO-A and MAO-B flavin-containing
      subunits have apparent molecular weights of 63,000 and 62,000 respectively. We
      have begun to assess the functional significance of embryonic quail MAO activity
      by daily injection of MAO inhibitors (clorgyline or clorgyline plus deprenyl)
      into fertilized eggs. Clorgyline injection selectively and completely inhibited
      MAO-A activity, while injection of clorgyline and deprenyl inhibited both MAO-A
      and MAO-B activities when embryos were assayed after either 2 or 7 days of
      embryonic development. This paradigm will allow a detailed examination of the
      effects of MAO inhibition on the developing embryo. 

PMID- 24875607
TI  - Phosphoglycerides and their acyl group composition in myelin and microsomes of
      rat spinal cord during development.
AB  - The phosphoglycerides and their acyl group composition in myelin and microsomes
      isolated from rat spinal cords were examined at various stages of the postnatal
      developmental period. In the immature cord, diacyl-GPC is the major
      phosphoglyceride in both microsomal and myelin fractions. The proportion of this
      phosphoglyceride decreased steadily with age during development and the decrease
      was marked by an increase in diacyl-GPE in microsomes and ethanolamine
      plasmalogen in both fractions. Marked changes in acyl group composition were
      observed in the microsomes during development of spinal cord, whereas acyl groups
      of myelin showed less extensive changes. A considerable amount of monoenoic fatty
      acid is already present in the myelin of 7-day-old cord. Acyl groups of diacyl
      GPC in the microsomal fraction indicated a decrease in 16:0, 16:1,20:4(n-6) and
      an increase in 18:0, 18:1 and 20:1 with respect to development. On the other
      hand, microsomal diacyl-GPE and alkenylacyl-GPE indicated a decrease in 16:0,
      18:0 and 20:4(n-6), but an increase in 18:1 and 20:1. An exception is the
      proportion of 22:6(n-3) which increased in diacyl-GPE and decreased in
      alkenylacyl-GPE during development. The lack of obvious acyl group changes in
      myelin phosphoglycerides after 7 days of age is in agreement with the results of
      deSousa & Horrocks (Devl Neurosci. 1, 114-120, 1979) that myelination in spinal
      cord took on an early course and reached the adult composition sooner than the
      cerebrum. 

PMID- 24875608
TI  - Lipid composition of gray and white matter in developing rat brain.
AB  - The lipid composition of gray and white matter was studied in the developing rat
      brain. For this purpose, gray and white matter were separated from the brains of
      rats from different age groups and were used for the estimation of moisture and
      lipids. The moisture content of both gray and white matter decreased with age,
      but the decrease was more significant in the latter. The concentration of
      different lipids in gray matter reached adult values at 4 weeks of age, whereas
      the lipids in white matter showed a slower increase even after this period.
      Similarly, the content of gray matter reached adult values much earlier (by 3
      weeks) than white matter, which continued to increase throughout the period of
      study. Myelin represented 40% of the dry weight of whitematter. The non-myelin
      portion of white matter had a different lipid composition than gray matter, white
      matter, or myelin. 

PMID- 24875609
TI  - Editorial.

PMID- 24875611
TI  - Radiographic changes after anterior cervical discectomy and their clinical
      impact.

PMID- 24875610
TI  - Sustained visual acuity loss in the comparison of age-related macular
      degeneration treatments trials.
AB  - IMPORTANCE: Although anti-vascular endothelial growth factor treatment of
      neovascular age-related macular degeneration (AMD) results in improved vision
      overall, loss of substantial vision can occur. Understanding the processes that
      lead to loss of vision may lead to preventive strategies. OBJECTIVE: To determine
      the incidence, characteristics, causes, and baseline predictors of sustained
      visual acuity loss after 2 years of treatment with ranibizumab or bevacizumab for
      neovascular AMD. DESIGN, SETTING, AND PARTICIPANTS: A cohort study within a
      randomized clinical trial of participants in the Comparison of Age-Related
      Macular Degeneration Treatments Trials (CATT). INTERVENTIONS: Participants were
      randomly assigned to treatment with ranibizumab or bevacizumab and to 2 years of
      monthly or as needed injections or monthly injections for 1 year and as needed
      injections the following year. MAIN OUTCOMES AND MEASURES: Sustained visual
      acuity loss, defined as loss of 15 or more letters from baseline at weeks 88 and
      104. RESULTS: Among 1030 participants, 61 eyes (5.9%) developed sustained visual
      acuity loss in 2 years. Within this group, visual acuity decreased gradually over
      time, with a mean decrease of 2, 19, and 33 letters from baseline at 4 weeks, 1
      year, and 2 years, respectively. At 2 years, eyes with sustained visual acuity
      loss had more scarring (60.0% vs 41.4%, P = .007), more geographic atrophy (GA)
      (31.6% vs 20.7%, P = .004), larger lesions (16 vs 8 mm2, P < .001), and higher
      proportions of intraretinal fluid (82.5% vs 51.0%, P < .001), subretinal
      hyperreflective material (84.5% vs 44.2%, P < .001), retinal thinning (43.3% vs
      23.0%, P < .001), and thickening (20.0% vs 12.1%, P < .001). Likely causes of
      sustained visual acuity loss included foveal scarring (44.3%), pigmentary
      abnormalities (27.9%), and foveal GA (11.5%). Baseline factors independently
      associated with a higher incidence of sustained visual acuity loss were the
      presence of nonfoveal GA (odds ratio [OR],  2.86; 95% CI, 1.35-6.08; P = .006),
      larger area of choroidal neovascularization (OR for a >4-disc area vs <=1-disc
      area, 3.91; 95% CI, 1.70-9.03; P = .007), and bevacizumab treatment (OR,  1.83;
      95% CI, 1.07-3.14; P = .03). CONCLUSIONS AND RELEVANCE: Sustained visual acuity
      loss was relatively rare in CATT. The development of foveal scar, pigmentary
      abnormalities, or GA contributed to most of the sustained visual acuity loss.
      Risk was 3% higher among eyes treated with bevacizumab. Treatment that targeted
      the prevention of scarring or GA may improve vision outcomes. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT00593450.

PMID- 24875612
TI  - Comparison of a collagen membrane versus a fibrin sealant after a peroneal nerve
      section and repair: a functional and histological study.
AB  - BACKGROUND: To date, fibrin sealant is considered to be one of the most effective
      substitutes to prevent post-operative fibrosis and to limit neuroma formation
      after nerve suture. Because fibrin sealant presents a number of drawbacks, more
      suitable techniques should be considered. The aim of this study was to
      functionally and histologically compare the efficiency of a fibrin sealant to a
      resorbable semi-permeable porcine type I collagen membrane after a peroneal nerve
      lesion and repair on rats. METHODS: Rats were divided into four groups: (1) a
      SHAM group (n = 10) in which surgery was performed without damaging the nerve,
      (2) a LESION group (n = 15) in which the nerve was cut and immediately sutured
      without additional treatment, (3) a MEMBRANE group (n = 30) in which a collagen
      membrane was wrapped around the lesion site, and (4) a GLUE group (n = 30) in
      which the peroneal nerve was coated by fibrin sealant. Peroneal Functional Index
      (PFI), kinematic analysis of locomotion, muscular atrophy, axonal regrowth, and
      irritant ranking score (IRS) were performed during three months post-surgery.
      RESULTS: Our results indicate that at the third month post-surgery, no difference
      in both the functional recovery and the histological measurement was observed
      between groups. However, no deleterious effect was observed following the use of
      the collagen membrane. Indeed, the porcine membrane was well-integrated into the
      host tissue, with no noticeable foreign body reaction at three months post
      surgery. CONCLUSION: Our preliminary results highlight the fact that the collagen
      membrane could be used as an alternative to fibrin sealant in peripheral nerve
      repair surgery. Indeed, animals in which the collagen membrane was used to wrap
      the lesion site exhibited similar functional and histological results as animals
      in which a fibrin sealant was used to coat the lesion. The greatest advantage of
      this membrane is that it could be used as a drug delivery device, regulated by
      its degradation rate.

PMID- 24875613
TI  - Long-term seizure outcome after stereotactic amygdalohippocampectomy.
AB  - BACKGROUND: The aim of the study was to evaluate the long-term seizure outcome
      and complications after stereotactic radiofrequency amygdalohippocampectomy
      (SAHE) performed for mesial temporal lobe epilepsy (MTLE). METHODS: The article
      describes the cases of 61 patients who were treated at our institution during the
      period 2004-2010. Mean post-operative follow-up was 5.3 years. RESULTS: At the
      last postsurgical visit, 43 (70.5 %) patients were Engel Class I, six (9.8 %)
      Class II, nine (14.8 %) Class III and three (4.9 %) Class IV. The surgery was
      complicated by four intracranial haematomas. One of them caused acute
      hydrocephalus and was treated by shunting and resolved without sequelae. After
      SAHE, we performed open epilepsy surgery and re-thermo lesions in three and two
      patients, respectively (8.2 %). There were two cases of meningitis which required
      antibiotic treatment. In six patients psychiatric disorders developed and one of
      these committed suicide due to postoperative depression. CONCLUSIONS: Our results
      provide preliminary evidence for good long-term seizure outcomes after SAHE. SAHE
      could be an alternative therapy for MTLE.

PMID- 24875615
TI  - VE-cadherin, a potential marker for endothelial cell activation during hereditary
      angioedema attacks.

PMID- 24875616
TI  - Reply: To PMID 24522092.

PMID- 24875614
TI  - Prospective memory on a novel clinical task in older adults with mild cognitive
      impairment and subjective cognitive decline.
AB  - Despite the relevance of prospective memory to everyday functioning and the
      ability to live independently, prospective memory tasks are rarely incorporated
      into clinical evaluations of older adults. We investigated the validity and
      clinical utility of a recently developed measure, the Royal Prince Alfred
      Prospective Memory Test (RPA-ProMem), in a demographically diverse, non-demented,
      community-dwelling sample of 257 older adults (mean age = 80.78 years, 67.7%
      female) with amnestic mild cognitive impairment (aMCI, n = 18), nonamestic mild
      cognitive impairment (naMCI, n = 38), subjective cognitive decline (SCD, n = 83)
      despite intact performance on traditional episodic memory tests, and healthy
      controls (HC, n = 118). Those with aMCI and naMCI performed significantly worse
      than controls on the RPA-ProMem and its subtasks (time-based, event-based, short
      term, long-term). Also, those with SCD scored significantly lower than controls
      on long-term, more naturalistic subtasks. Additional results supported the
      validity and inter-rater reliability of the RPA-ProMem and demonstrated a
      relation between test scores and informant reports of real-world functioning. The
      RPA-ProMem may help detect subtle cognitive changes manifested by individuals in
      the earliest stages of dementia, which may be difficult to capture with
      traditional episodic memory tests. Also, assessment of prospective memory can
      help guide the development of cognitive interventions for older adults at risk
      for dementia. 

PMID- 24875617
TI  - Cow's milk allergy and the association between fatty acids and childhood asthma
      risk.

PMID- 24875619
TI  - Economic and health effect of full adherence to controller therapy in adults with
      uncontrolled asthma: a simulation study.
AB  - BACKGROUND: Adherence to evidence-based controller treatments for asthma is
      disappointingly low in many jurisdictions. Quantifying the burden associated with
      suboptimal adherence in patients with uncontrolled asthma will help establish the
      priorities for policymakers. OBJECTIVE: We sought to quantify the benefits in the
      United States of improving adherence to controller therapies in adults with
      uncontrolled asthma in terms of health care costs and quality-adjusted life years
      (QALYs). METHODS: A Markov model of asthma was created to simulate the effect of
      treatment with controller medications on asthma control and exacerbations over a
      10-year time horizon. Health care costs and QALYs associated with the current
      level of adherence (status quo) were compared with a hypothetical scenario in
      which each patient with uncontrolled asthma at baseline will be fully adherent to
      an evidence-based controller therapy (the full-adherence scenario). We also
      evaluated the cost-effectiveness of adherence interventions as a function of
      their costs and improvement in the adherence. RESULTS: The status quo level of
      asthma management was associated with $2,786 costs and 7.55 QALYs over 10 years,
      whereas the corresponding values for the full-adherence scenario were $5,973 and
      7.68, respectively. Consequently, the incremental cost-effectiveness ratio of the
      full-adherence versus the status quo was $24,515/QALY. To be cost-effective, a
      program that improves adherence by 50% should cost less than $130 ($450) per
      person annually at a willingness-to-pay value of $50,000/QALY ($100,000/QALY).
      Inclusion of productivity loss in the analysis resulted in the full-adherence
      scenario being cost-saving. CONCLUSION: Considering the extent of suboptimal
      adherence, our study shows that attempts in improving adherence to evidence-based
      therapies in patients with uncontrolled asthma can be associated with significant
      return on investment.

PMID- 24875620
TI  - What do we know about Lorentz invariance?
AB  - The realization that Planck-scale physics can be tested with existing technology
      through the search for spacetime-symmetry violation brought about the development
      of a comprehensive framework, known as the gravitational standard-model extension
      (SME), for studying deviations from exact Lorentz and CPT symmetry in nature. The
      development of this framework and its motivation led to an explosion of new tests
      of Lorentz symmetry over the past decade and to considerable theoretical interest
      in the subject. This work reviews the key concepts associated with Lorentz and
      CPT symmetry, the structure of the SME framework, and some recent experimental
      and theoretical results. 

PMID- 24875618
TI  - Asthmatic airway epithelial cells differentially regulate fibroblast expression
      of extracellular matrix components.
AB  - BACKGROUND: Airway remodeling might explain lung function decline among asthmatic
      children. Extracellular matrix (ECM) deposition by human lung fibroblasts (HLFs)
      is implicated in airway remodeling. Airway epithelial cell (AEC) signaling might
      regulate HLF ECM expression. OBJECTIVES: We sought to determine whether AECs from
      asthmatic children differentially regulate HLF expression of ECM constituents.
      METHODS: Primary AECs were obtained from well-characterized atopic asthmatic (n =
      10) and healthy (n = 10) children intubated during anesthesia for an elective
      surgical procedure. AECs were differentiated at an air-liquid interface for 3
      weeks and then cocultured with HLFs from a healthy child for 96 hours. Collagen I
      (COL1A1), collagen III (COL3A1), hyaluronan synthase (HAS) 2, and fibronectin
      expression by HLFs and prostaglandin E2 synthase (PGE2S) expression by AECs were
      assessed by using RT-PCR. TGF-beta1 and TGF-beta2 concentrations in media were
      measured by using ELISA. RESULTS: COL1A1 and COL3A1 expression by HLFs cocultured
      with AECs from asthmatic patients was greater than that by HLFs cocultured with
      AECs from healthy subjects (2.2-fold, P < .02; 10.8-fold, P < .02). HAS2
      expression by HLFs cocultured with AECs from asthmatic patients was 2.5-fold
      higher than that by HLFs cocultured with AECs from healthy subjects (P < .002).
      Fibronectin expression by HLFs cocultured with AECs from asthmatic patients was
      significantly greater than that by HLFs alone. TGF-beta2 activity was increased
      in cocultures of HLFs with AECs from asthmatic patients (P < .05), whereas PGES2
      was downregulated in AEC-HLF cocultures (2.2-fold, P < .006). CONCLUSIONS: HLFs
      cocultured with AECs from asthmatic patients showed differential expression of
      the ECM constituents COL1A1 and COL3A1 and HAS2 compared with HLFs cocultured
      with AECs from healthy subjects. These findings support a role for altered ECM
      production in asthmatic airway remodeling, possibly regulated by unbalanced AEC
      signaling.

PMID- 24875622
TI  - A real-time 3D video tracking system for monitoring primate groups.
AB  - To date, assessing the solitary and social behaviors of laboratory primates'
      colonies relies on time-consuming manual scoring methods. Here, we describe a
      real-time multi-camera 3D tracking system developed to measure the behavior of
      socially-housed primates. Their positions are identified using non-invasive color
      markers such as plastic collars, thus allowing to also track colored objects and
      to measure their usage. Compared to traditional manual ethological scoring, we
      show that this system can reliably evaluate solitary behaviors (foraging,
      solitary resting, toy usage, locomotion) as well as spatial proximity with peers,
      which is considered as a good proxy of their social motivation. Compared to
      existing video-based commercial systems currently available to measure animal
      activity, this system offers many possibilities (real-time data, large volume
      coverage, multiple animal tracking) at a lower hardware cost. Quantitative
      behavioral data of animal groups can now be obtained automatically over very long
      periods of time, thus opening new perspectives in particular for studying the
      neuroethology of social behavior in primates. 

PMID- 24875621
TI  - Cooperativity and equilibrium with FOXA1 define the androgen receptor
      transcriptional program.
AB  - The pioneering factor FOXA1 opens chromatin to facilitate androgen receptor (AR)
      binding to prostate-specific genes. How FOXA1 controls the AR cistrome, however,
      is incompletely understood. Here we show that AR directly binds chromatin through
      the androgen response elements (AREs). FOXA1 is not required for AR-chromatin
      interaction, but instrumental in recruiting AR to low-affinity half-AREs by
      opening local chromatin around adjacent FKHD sites. Too much FOXA1 creates
      excessive open chromatin regions, which serve as reservoirs that retain AR via
      abundant half-AREs, thereby reducing its availability for specific sites. FOXA1
      downregulation, by contrast, relinquishes AR to permissively bind AREs across the
      genome, resulting in substantial AR-binding events and AR target gene expression
      even in the absence of androgen. Taken together, our data illustrate the
      mechanistic details by which cooperativity and equilibrium with FOXA1 define AR
      cistrome and reveal a previously unknown function of FOXA1 in inhibiting AR
      signalling and castration-resistant prostate cancer growth. 

PMID- 24875623
TI  - Methods for estimating cortical motor representation size and location in
      navigated transcranial magnetic stimulation.
AB  - BACKGROUND: Navigated transcranial magnetic stimulation (nTMS) is used for
      locating and outlining cortical representation areas, e.g., of motor function and
      speech. At present there are no standard methods of measuring the size of the
      cortical representation areas mapped with nTMS. The aim was to compare four
      computation methods for estimating muscle representation size and location for
      nTMS studies. NEW METHOD: The motor cortex of six subjects was mapped to outline
      the motor cortical representation of hand muscles. Four methods were compared to
      assess cortical representation size in nTMS. These methods included: (1) spline
      interpolation method, (2) convex hull method, which outlines all positive motor
      responses, (3) Voronoi tessellation method, which assigns a specific cortical
      area for each stimulus location, and (4) average point-area method, which
      computes an average representation area for each stimulus with the assumption of
      evenly spaced stimulus locations, i.e., the use of a grid. RESULTS: All applied
      methods demonstrated good repeatability in measuring muscle representation size
      and location, while the spline interpolation and the convex hull method
      demonstrated systematically larger representation areas (p<0.05) as compared to
      the average point-area method. Spline interpolation method demonstrated the best
      repeatability in location. COMPARISON WITH EXISTING METHODS: Unlike the previous
      methods, the presented methods can be applied for the estimation of the
      representation area of nTMS-induced activation without the use of an evenly
      spaced stimulus grid. CONCLUSIONS: The spline interpolation method and the
      Voronoi tessellation method could be used for evaluating motor cortical muscle
      representation size and location with nTMS, e.g., to study cortical plasticity.

PMID- 24875624
TI  - An efficient seizure prediction method using KNN-based undersampling and linear
      frequency measures.
AB  - Seizure prediction based on analysis of electroencephalogram signals has
      generated considerable research interests. A reliable seizure prediction
      algorithm with minimal computational requirements is prominent issue for medical
      facilities; however, it has not been addressed correctly. In this study, an
      optimized novel method is proposed in order to remove computational complexity,
      and predict epileptic seizures clinically. It is based on the univariate linear
      features in eight frequency sub-bands. It also employs principal component
      analysis (PCA) for dimension reduction and optimal feature selection. Class
      unbalanced problem is tackled by K-nearest neighbor (KNN)-based undersampling
      combined with support vector machine (SVM) classifier. To find out the best
      results two types of postprocessing methods were studied. The proposed algorithm
      was evaluated on seizures and 434.9h of interictal data from 18 patients of
      Freiburg database. It predicted 100% of seizures with average false alarm rate of
      0.13 per hour ranging between 0 and 0.39. Furthermore, G-Mean and F-measure were
      used for validation which were 0.97 and 0.90, respectively. These results
      confirmed the discriminative ability of the algorithm. In comparison with other
      studies, the proposed method improves trade-off between sensitivity and false
      prediction rate with linear features and low computational requirements and it
      can potentially be employed in implantable devices. Achieving high performance by
      linear features, PCA, KNN-based undersampling, and SVM demonstrates that this
      method can potentially be used in implantable devices. 

PMID- 24875625
TI  - Synergistic combination therapy using a lipid shell-droplet core nanosphere with
      tunable thickness.
AB  - A newly-designed drug carrier composed of an internal droplet core and a
      thickness-controllable shell was successfully developed. By co-delivering
      paclitaxel, doxorubicin and quantum dots simultaneously, this combinational drug
      delivery system could achieve in vitro fluorescence imaging, chemotherapeutic and
      oxidation therapy. 

PMID- 24875626
TI  - Identification of a novel strong and ubiquitous promoter/enhancer in the silkworm
      Bombyx mori.
AB  - Transgenic techniques offer a valuable tool for determining gene functions.
      Although various promoters are available for use in gene overexpression, gene
      knockdown, and identification of transgenic individuals, there is nevertheless a
      lack of versatile promoters for such studies, and this dearth acts as a
      bottleneck, especially with regard to nonmodel organisms. Here, we succeeded in
      identifying a novel strong and ubiquitous promoter/enhancer in the silkworm. We
      identified a unique silkworm strain whose reporter gene showed strong and
      ubiquitous expression during the establishment of enhancer trap strains. In this
      strain, the transposon was inserted into the 5'UTR of hsp90, a housekeeping gene
      that is abundantly expressed in a range of tissues. To determine whether the
      promoter/enhancer of hsp90 could be used to induce strong gene expression, a 2.9
      kb upstream genomic fragment of hsp90 was isolated (hsp90(P2.9k)), and its
      transcriptional activation activity was examined. Strikingly, hsp90(P2.9k)
      induced strong gene expression in silkworm cell cultures and also strongly
      induced gene expression in various tissues and developmental stages of the
      silkworm. hsp90(P2.9k) also exhibited significant promoter/enhancer activity in
      Sf9, a cell culture from the armyworm, suggesting that this fragment might
      possibly be used as a gene expression tool in other Lepidoptera. We further found
      that 2.0 kb of hsp90(P2.9k) is sufficient for the induction of strong gene
      expression. We believe that this element will be of value for a range of studies
      such as targeted gene overexpression, gene knockdown and marker gene expression,
      not only in the silkworm but also in other insect species. 

PMID- 24875628
TI  - RNA-guided genome editing in Drosophila with the purified Cas9 protein.
AB  - We report a method for generating Drosophila germline mutants effectively via
      injection of the complex of the purified Cas9 protein, tracrRNA, and gene
      specific crRNAs, which may reduce delayed mutations because of the transient
      activity of the Cas9 protein, combined with the simple mutation detection in GO
      founders by the T7E1 assay. 

PMID- 24875627
TI  - Functional conservation of the pre-sensor one beta-finger hairpin (PS1-hp)
      structures in mini-chromosome maintenance proteins of Saccharomyces cerevisiae
      and archaea.
AB  - Mini-chromosome maintenance (MCM) proteins form complexes that are required for
      DNA replication and are highly conserved throughout evolution. The replicative
      helicase of eukaryotic organisms is composed of the six paralogs MCM2-7, which
      form a heterohexameric ring structure. In contrast, the structure of the archaean
      replicative MCM helicase is a single Mcm protein that forms a homohexameric
      complex. Atomic structures of archaeal MCMs have identified multiple beta-finger
      structures in Mcm proteins whose in vivo function is unknown. In the present
      study, we have investigated the physiological role of the pre-sensor 1 beta
      hairpin (PS1-hp) beta-fingers of Saccharomyces cerevisiae Mcm4p and Mcm5p in DNA
      replication initiation and elongation in vivo. The PS1-hp beta-finger mutant of
      Mcm5p (mcm5-HAT K506A::URA3) has a growth defect at both 18 degrees  and 37
      degrees . Mutation of the Mcm4p PS1-hp beta-finger (mcm4-HA K658A::TRP1) does not
      have a growth defect, indicating different functional contributions of the PS1-hp
      beta-finger structures of different MCM helicase subunits. Both Mcm4p and Mcm5p
      PS1-hp beta-finger mutants can coimmunoprecipitate Mcm2p, indicating the
      formation of the hexameric MCM helicase complex. Both PS1-hp beta-finger mutants
      have a plasmid loss phenotype that is suppressible by origin dosage, indicating a
      defective replication initiation. Surprisingly, a defect in the binding of PS1-hp
      MCM mutants to origins of DNA replication was not found by chromatin
      immunoprecipitation, suggesting a novel interpretation in which the defect is in
      a subsequent step of DNA strand separation by the MCM helicase. The double mutant
      mcm4-HA K658A::TRP1 mcm5-HAT K506A::URA3 is lethal, displaying a terminal MCM
      mutant phenotype of large budded cells. 

PMID- 24875631
TI  - Is the study of mortality reduction alone indicating the effectiveness of the
      guideline?

PMID- 24875630
TI  - Validation of six genetic determinants of susceptibility to estrogen-induced
      mammary cancer in the rat and assessment of their relevance to breast cancer risk
      in humans.
AB  - When treated with 17beta-estradiol, female ACI rats (Rattus norvegicus) rapidly
      develop mammary cancers that share multiple phenotypes with luminal breast
      cancers. Seven distinct quantitative trait loci that harbor genetic determinants
      of susceptibility to 17beta-estradiol-induced mammary cancer have been mapped in
      reciprocal intercrosses between susceptible ACI rats and resistant Brown Norway
      (BN) rats. A panel of unique congenic rat strains has now been generated and
      characterized to confirm the existence of these quantitative trait loci,
      designated Emca3 through Emca9, and to quantify their individual effects on
      susceptibility to 17beta-estradiol-induced mammary cancer. Each congenic strain
      carries BN alleles spanning an individual Emca locus, introgressed onto the ACI
      genetic background. Data presented herein indicate that BN alleles at Emca3,
      Emca4, Emca5, Emca6, and Emca9 reduce susceptibility to 17beta-estradiol-induced
      mammary cancer, whereas BN alleles at Emca7 increase susceptibility, thereby
      confirming the previous interval mapping data. All of these Emca loci are
      orthologous to regions of the human genome that have been demonstrated in genome
      wide association studies to harbor genetic variants that influence breast cancer
      risk. Moreover, four of the Emca loci are orthologous to loci in humans that have
      been associated with mammographic breast density, a biomarker of breast cancer
      risk. This study further establishes the relevance of the ACI and derived
      congenic rat models of 17beta-estradiol-induced mammary cancer for defining the
      genetic bases of breast cancer susceptibility and elucidating the mechanisms
      through which 17beta-estradiol contributes to breast cancer development. 

PMID- 24875629
TI  - Essential domains of Schizosaccharomyces pombe Rad8 required for DNA damage
      response.
AB  - Schizosaccharomyces pombe Rad8 is a conserved protein homologous to S. cerevisiae
      Rad5 and human HLTF that is required for error-free postreplication repair by
      contributing to polyubiquitylation of PCNA. It has three conserved domains: an E3
      ubiquitin ligase motif, a SNF2-family helicase domain, and a family-specific
      HIRAN domain. Data from humans and budding yeast suggest that helicase activity
      contributes to replication fork regression and template switching for fork
      restart. We constructed specific mutations in the three conserved domains and
      found that both the E3 ligase and HIRAN domains are required for proper response
      to DNA damage caused by a variety of agents. In contrast, mutations in the
      helicase domain show no phenotypes in a wild-type background. To determine
      whether Rad8 functionally overlaps with other helicases, we compared the
      phenotypes of single and double mutants with a panel of 23 nonessential helicase
      mutants, which we categorized into five phenotypic groups. Synthetic phenotypes
      with rad8? were observed for mutants affecting recombination, and a rad8 helicase
      mutation affected the HU response of a subset of recombination mutants. Our data
      suggest that the S. pombe Rad8 ubiquitin ligase activity is important for
      response to a variety of damaging agents, while the helicase domain plays only a
      minor role in modulating recombination-based fork restart during specific forms
      of replication stress. 

PMID- 24875632
TI  - Associations between muscle-related cytokines and selected patient outcomes in
      the ICU.
AB  - INTRODUCTION: Systemic cytokines produced by contracting skeletal muscles may
      affect the onset and severity of intensive care unit (ICU)-acquired weakness
      after critical illness. AIMS: The purpose of this research was to determine the
      serum levels of interleukin (IL)-8, IL-15, and tumor necrosis factor-alpha (TNF
      alpha) among patients receiving mechanical ventilation for >48 hr and examine the
      relationships of these myokines to outcomes of patient delirium, muscle strength,
      activities of daily living (ADLs), duration of mechanical ventilation, and length
      of ICU stay. METHODS: In this exploratory, repeated-measures interventional
      study, the 36 participants received 20 min of once-daily in-bed or out-of-bed
      activity using an established early progressive mobility protocol after
      physiologic stability had been demonstrated for >4 hr in the ICU. Blood samples
      were drawn on 3 consecutive days, beginning on the day of study enrollment, for
      serum cytokine quantification. RESULTS: IL-8, IL-15, and TNF-alpha were highly
      variable and consistently elevated in participants compared to normal healthy
      adults. About 1/3 of participants were positive for significant muscle weakness
      at discharge from ICU. Repeated values of mean postactivity IL-8 serum values
      were significantly associated only with ADL following ICU discharge. There were
      no significant associations with repeated values of mean postactivity IL-15 or
      TNF-alpha serum values and outcomes. CONCLUSION: Results provide preliminary data
      for exploring the potential effects of elevated serum values IL-8 and IL-15 in
      muscle health and TNF-alpha for muscle damage, including effect sizes to
      calculate the sample sizes needed for future studies.

PMID- 24875635
TI  - Nitrogen-Vacancy color center in diamond-emerging nanoscale applications in
      bioimaging and biosensing.
AB  - Nitrogen-Vacancy (NV) color center in diamond is a flourishing research area
      that, in recent years, has displayed remarkable progress. The system offers great
      potential for realizing futuristic applications in nanoscience, benefiting a
      range of fields from bioimaging to quantum-sensing. The ability to image single
      NV color centers in a nanodiamond and manipulate NV electron spin optically under
      ambient condition is the main driving force behind developments in nanoscale
      sensing and novel imaging techniques. In this article we discuss current status
      on the applications of fluorescent nanodiamonds (FND) for optical super
      resolution nanoscopy, magneto-optical (spin-assisted) sub-wavelength localization
      and imaging. We present emerging applications such as single molecule spin
      imaging, nanoscale imaging of biomagnetic fields, sensing molecular fluctuations
      and temperatures in live cellular environments. We summarize other current
      advances and future prospects of NV diamond for imaging and sensing pertaining to
      bio-medical applications. 

PMID- 24875636
TI  - Advances in live-cell single-particle tracking and dynamic super-resolution
      imaging.
AB  - Resolving the movement of individual molecules in living cells by single particle
      tracking methods has allowed many molecular behaviors to be deciphered over the
      past three decades. These methods have increasingly benefited from advances in
      microscopy of single nano-objects such as fluorescent dye molecules, proteins or
      nanoparticles as well as tiny absorbing metal nanoparticles. In parallel to these
      efforts aiming at tracking ever smaller and more photostable nano-objects in
      living cells, the development of localization-based super-resolution imaging
      provided means to increase the number of single molecules tracked on a single
      cell. In this review we will present the most recent advances in the field. 

PMID- 24875633
TI  - Chemical and enzymatic fractionation of cell walls from Fucales: insights into
      the structure of the extracellular matrix of brown algae.
AB  - BACKGROUND AND AIMS: Brown algae are photosynthetic multicellular marine
      organisms evolutionarily distant from land plants, with a distinctive cell wall.
      They feature carbohydrates shared with plants (cellulose), animals (fucose
      containing sulfated polysaccharides, FCSPs) or bacteria (alginates). How these
      components are organized into a three-dimensional extracellular matrix (ECM)
      still remains unclear. Recent molecular analysis of the corresponding
      biosynthetic routes points toward a complex evolutionary history that shaped the
      ECM structure in brown algae. METHODS: Exhaustive sequential extractions and
      composition analyses of cell wall material from various brown algae of the order
      Fucales were performed. Dedicated enzymatic degradations were used to release and
      identify cell wall partners. This approach was complemented by systematic
      chromatographic analysis to study polymer interlinks further. An additional
      structural assessment of the sulfated fucan extracted from Himanthalia elongata
      was made. KEY RESULTS: The data indicate that FCSPs are tightly associated with
      proteins and cellulose within the walls. Alginates are associated with most
      phenolic compounds. The sulfated fucans from H. elongata were shown to have a
      regular alpha-(1->3) backbone structure, while an alternating alpha-(1->3), (1
      >4) structure has been described in some brown algae from the order Fucales.
      CONCLUSIONS: The data provide a global snapshot of the cell wall architecture in
      brown algae, and contribute to the understanding of the structure-function
      relationships of the main cell wall components. Enzymatic cross-linking of
      alginates by phenols may regulate the strengthening of the wall, and sulfated
      polysaccharides may play a key role in the adaptation to osmotic stress. The
      emergence and evolution of ECM components is further discussed in relation to the
      evolution of multicellularity in brown algae.

PMID- 24875634
TI  - Blood cis-eQTL analysis fails to identify novel association signals among sub
      threshold candidates from genome-wide association studies in restless legs
      syndrome.
AB  - Restless legs syndrome (RLS) is a common neurologic disorder characterized by
      nightly dysesthesias affecting the legs primarily during periods of rest and
      relieved by movement. RLS is a complex genetic disease and susceptibility factors
      in six genomic regions have been identified by means of genome-wide association
      studies (GWAS). For some complex genetic traits, expression quantitative trait
      loci (eQTLs) are enriched among trait-associated single nucleotide polymorphisms
      (SNPs). With the aim of identifying new genetic susceptibility factors for RLS,
      we assessed the 332 best-associated SNPs from the genome-wide phase of the to
      date largest RLS GWAS for cis-eQTL effects in peripheral blood from individuals
      of European descent. In 740 individuals belonging to the KORA general population
      cohort, 52 cis-eQTLs with pnominal<10(-3) were identified, while in 976
      individuals belonging to the SHIP-TREND general population study 53 cis-eQTLs
      with pnominal<10(-3) were present. 23 of these cis-eQTLs overlapped between the
      two cohorts. Subsequently, the twelve of the 23 cis-eQTL SNPs, which were not
      located at an already published RLS-associated locus, were tested for association
      in 2449 RLS cases and 1462 controls. The top SNP, located in the DET1 gene, was
      nominally significant (p<0.05) but did not withstand correction for multiple
      testing (p = 0.42). Although a similar approach has been used successfully with
      regard to other complex diseases, we were unable to identify new genetic
      susceptibility factor for RLS by adding this novel level of functional assessment
      to RLS GWAS data.

PMID- 24875637
TI  - Tuberculosis vaccines--rethinking the current paradigm.
AB  - The vaccine discovery paradigm in tuberculosis (TB) has been to mimic the natural
      immune response to infection. With an emphasis on interferon (IFN)-gamma as the
      main protective cytokine, researchers have selected dominant antigens and
      administered them in delivery systems to promote strong T helper (Th)1 responses.
      However, the Bacillus Calmette-Guerin (BCG) vaccine is a strong inducer of Th1
      cells, yet has limited protection in adults, and further boosting by the Modified
      Vaccinia-Ankara (MVA)85A vaccine failed to enhance efficacy in a clinical trial.
      We review the current understanding of host-pathogen interactions in TB infection
      and propose that rather than boosting Th1 responses, we should focus on
      understanding protective immune responses that are lacking or insufficiently
      promoted by BCG that can intervene at critical stages of the TB life cycle. 

PMID- 24875640
TI  - Different micro-RNA expression profiles distinguish subtypes of neuroendocrine
      tumors of the lung: results of a profiling study.
AB  - MicroRNAs (miRNAs) are a class of small (~22 nucleotides), non-coding, highly
      conserved single-stranded RNAs with posttranscriptional regulatory features,
      including the regulation of cell proliferation, differentiation, survival, and
      apoptosis. They are deregulated in a broad variety of tumors showing
      characteristic expression patterns and can, thus, be used as a diagnostic tool.
      In contrast to non-small cell carcinoma of the lung neuroendocrine lung tumors,
      encompassing typical and atypical carcinoids, small cell lung cancer and large
      cell neuroendocrine lung cancer, no data about deregulation of tumor entity
      specific miRNAs are available to date. miRNA expression differences might give
      useful information about the biological characteristics of these tumors, as well
      as serve as helpful markers.In 12 pulmonary neuroendocrine tumors classified as
      either typical carcinoid, atypical, large cell neuroendocrine or small cell lung
      cancer, screening for 763 miRNAs known to be involved in pulmonary cancerogenesis
      was conducted by performing 384-well TaqMan low-density array real-time qPCR. In
      the entire cohort, 44 miRNAs were identified, which showed a significantly
      different miRNA expression. For 12 miRNAs, the difference was highly significant
      (P<0.01). Eight miRNAs showed a negative (miR-22, miR-29a, miR-29b, miR-29c, miR
      367*; miR-504, miR-513C, miR-1200) and four miRNAs a positive (miR-18a, miR-15b*,
      miR-335*, miR-1201) correlation to the grade of tumor biology. The miRNAs let-7d;
      miR-19; miR-576-5p; miR-340*; miR-1286 are significantly associated with
      survival. Members of the miR-29 family seem to be extremely important in this
      group of tumors. We found a number of miRNAs, which showed a highly significant
      deregulation in pulmonary neuroendocrine tumors. Moreover, some of these
      deregulated miRNAs seem to allow discrimination of the various subtypes of
      pulmonary neuroendocrine tumors. Thus, the analysis of specific sets of miRNAs
      can be proposed as diagnostic and/or predictive markers in this group of
      neoplasias. 

PMID- 24875638
TI  - Synchronization of developmental processes and defense signaling by growth
      regulating transcription factors.
AB  - Growth regulating factors (GRFs) are a conserved class of transcription factor in
      seed plants. GRFs are involved in various aspects of tissue differentiation and
      organ development. The implication of GRFs in biotic stress response has also
      been recently reported, suggesting a role of these transcription factors in
      coordinating the interaction between developmental processes and defense
      dynamics. However, the molecular mechanisms by which GRFs mediate the overlaps
      between defense signaling and developmental pathways are elusive. Here, we report
      large scale identification of putative target candidates of Arabidopsis GRF1 and
      GRF3 by comparing mRNA profiles of the grf1/grf2/grf3 triple mutant and those of
      the transgenic plants overexpressing miR396-resistant version of GRF1 or GRF3. We
      identified 1,098 and 600 genes as putative targets of GRF1 and GRF3,
      respectively. Functional classification of the potential target candidates
      revealed that GRF1 and GRF3 contribute to the regulation of various biological
      processes associated with defense response and disease resistance. GRF1 and GRF3
      participate specifically in the regulation of defense-related transcription
      factors, cell-wall modifications, cytokinin biosynthesis and signaling, and
      secondary metabolites accumulation. GRF1 and GRF3 seem to fine-tune the crosstalk
      between miRNA signaling networks by regulating the expression of several miRNA
      target genes. In addition, our data suggest that GRF1 and GRF3 may function as
      negative regulators of gene expression through their association with other
      transcription factors. Collectively, our data provide new insights into how GRF1
      and GRF3 might coordinate the interactions between defense signaling and plant
      growth and developmental pathways. 

PMID- 24875641
TI  - Measuring static seated pressure distributions and risk for skin pressure
      ulceration in ice sledge hockey players.
AB  - PURPOSE: To determine whether sledge hockey players with physical disability have
      higher average seated pressures compared to non-disabled controls. METHOD:
      Fifteen age-matched controls without physical disability and 15 experimental
      participants with physical disability were studied using a pressure mapping
      device to determine risk for skin pressure ulceration and the impact of
      cushioning and knee angle positioning on seated pressure distributions. RESULTS:
      Regardless of participant group, cushioning, or knee angle, average seated
      pressures exceeded clinically acceptable seated pressures. Controls had
      significantly higher average seated pressures than the disability group when
      knees were flexed, both with the cushion (p = 0.013) and without (p = 0.015).
      Knee extension showed significantly lower average pressures in controls, both
      with the cushion (p < 0.001) and without (p < 0.001). Placement of the cushion
      resulted in significantly lower average pressure in controls when knees were
      extended (p = 0.024) but not when flexed (p = 0.248). Placement of the cushion
      resulted in no difference in pressure (p = 0.443) in the disability group.
      CONCLUSIONS: Pressures recorded indicate high risk for skin ulceration.
      Cushioning was effective only in the control group with knees extended. That knee
      extension significantly lowered average seated pressures is important, as many
      sledge hockey players utilize positioning with larger knee flexion angles.
      Implications for Rehabilitation Ice sledge hockey is a fast growing adaptive
      sport. Adaptive sports have been associated with several positive improvements in
      overall health and quality of life, though may be putting players at risk for
      skin ulceration. Measured static seated pressure in sledges greatly exceeds
      current clinically accepted clinical guidelines. With modern improvements in
      wheelchair pressure relief/cushioning there are potential methods for improvement
      of elevated seated pressure in ice hockey sledges.

PMID- 24875639
TI  - Skeletal muscle contractions induce acute changes in cytosolic superoxide, but
      slower responses in mitochondrial superoxide and cellular hydrogen peroxide.
AB  - Skeletal muscle generation of reactive oxygen species (ROS) is increased
      following contractile activity and these species interact with multiple signaling
      pathways to mediate adaptations to contractions. The sources and time course of
      the increase in ROS during contractions remain undefined. Confocal microscopy
      with specific fluorescent probes was used to compare the activities of superoxide
      in mitochondria and cytosol and the hydrogen peroxide content of the cytosol in
      isolated single mature skeletal muscle (flexor digitorum brevis) fibers prior to,
      during, and after electrically stimulated contractions. Superoxide in
      mitochondria and cytoplasm were assessed using MitoSox red and dihydroethidium
      (DHE) respectively. The product of superoxide with DHE, 2-hydroxyethidium (2-HE)
      was acutely increased in the fiber cytosol by contractions, whereas hydroxy
      MitoSox showed a slow cumulative increase. Inhibition of nitric oxide synthases
      increased the contraction-induced formation of hydroxy-MitoSox only with no
      effect on 2-HE formation. These data indicate that the acute increases in
      cytosolic superoxide induced by contractions are not derived from mitochondria.
      Data also indicate that, in muscle mitochondria, nitric oxide (NO) reduces the
      availability of superoxide, but no effect of NO on cytosolic superoxide
      availability was detected. To determine the relationship of changes in superoxide
      to hydrogen peroxide, an alternative specific approach was used where fibers were
      transduced using an adeno-associated viral vector to express the hydrogen
      peroxide probe, HyPer within the cytoplasmic compartment. HyPer fluorescence was
      significantly increased in fibers following contractions, but surprisingly
      followed a relatively slow time course that did not appear directly related to
      cytosolic superoxide. These data demonstrate for the first time temporal and site
      specific differences in specific ROS that occur in skeletal muscle fibers during
      and after contractile activity. 

PMID- 24875643
TI  - The evolutionarily conserved mediator subunit MDT-15/MED15 links protective
      innate immune responses and xenobiotic detoxification.
AB  - Metazoans protect themselves from environmental toxins and virulent pathogens
      through detoxification and immune responses. We previously identified a small
      molecule xenobiotic toxin that extends survival of Caenorhabditis elegans
      infected with human bacterial pathogens by activating the conserved p38 MAP
      kinase PMK-1 host defense pathway. Here we investigate the cellular mechanisms
      that couple activation of a detoxification response to innate immunity. From an
      RNAi screen of 1,420 genes expressed in the C. elegans intestine, we identified
      the conserved Mediator subunit MDT-15/MED15 and 28 other gene inactivations that
      abrogate the induction of PMK-1-dependent immune effectors by this small
      molecule. We demonstrate that MDT-15/MED15 is required for the xenobiotic-induced
      expression of p38 MAP kinase PMK-1-dependent immune genes and protection from
      Pseudomonas aeruginosa infection. We also show that MDT-15 controls the induction
      of detoxification genes and functions to protect the host from bacteria-derived
      phenazine toxins. These data define a central role for MDT-15/MED15 in the
      coordination of xenobiotic detoxification and innate immune responses. 

PMID- 24875644
TI  - Supplementing with Opuntia ficus-indica Mill and Dioscorea nipponica Makino
      extracts synergistically attenuates menopausal symptoms in estrogen-deficient
      rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Prickly pear cactus grown in Korea (Opuntia ficus
      indica Mill, KC) and Buchema (Dioscorea nipponica Makino, B) have been
      traditionally used in East Asia and South America to treat various metabolic
      diseases. The aim of the present study was to determine whether the extracts of
      KC, B, and KC+B can prevent the impairments of energy, glucose, lipid and bone
      homeostasis in estrogen-deficient ovariectomized (OVX) rats and to explore their
      mechanisms. MATERIALS AND METHODS: OVX rats were divided into 4 groups and fed
      high fat diets supplemented with either 3% dextrin (control), 3% KC, 3% B or 1.5%
      KC+1.5% B. Sham rats were fed 3% dextrin. After 12 weeks of diet consumption,
      energy, lipid, glucose and bone metabolisms were analyzed and Wnt signaling in
      the femur and hepatic signaling were determined. RESULTS: OVX impaired energy,
      glucose and lipid metabolism and decreased uterine and bone masses. B and KC+B
      prevented the decrease in energy expenditure, especially from fat oxidation, in
      OVX rats, but did not affect food intake. KC+B and B reduced body weight and
      visceral fat levels, as compared to the OVX-control, by decreasing fat synthesis
      and inhibiting FAS and SREBP-1c expression. KC+B and B prevented the increases in
      serum lipid levels and insulin resistance by improving hepatic insulin signaling
      (pIRS->pAkt->pGSK-3beta). KC and KC+B also prevented decreases in bone mineral
      density (BMD) in the femur and lumbar spine in OVX rats. This was related to
      decreased expressions of bone turnover markers such as serum osteocalcin,
      alkaline phosphatase (ALP) and bone-specific ALP levels, and increased serum P
      levels. KC and KC+B upregulated low-density lipoprotein receptor-related protein
      5 and beta-catenin in OVX rats, but suppressed the expression of dickkopf-related
      protein 1. B alone improved energy, lipid and glucose homeostasis, but not bone
      loss, whereas KC alone enhanced BMD, but not energy, lipid or glucose
      homeostasis. CONCLUSION: KC+B synergistically attenuated impairments of bone,
      energy, lipid and glucose metabolism by OVX, suggesting potential efficacy of the
      combination for alleviating menopausal symptoms.

PMID- 24875642
TI  - Thioredoxin reductase and its inhibitors.
AB  - Thioredoxin plays a crucial role in a wide number of physiological processes,
      which span from reduction of nucleotides to deoxyriboucleotides to the
      detoxification from xenobiotics, oxidants and radicals. The redox function of
      Thioredoxin is critically dependent on the enzyme Thioredoxin NADPH Reductase
      (TrxR). In view of its indirect involvement in the above mentioned
      physio/pathological processes, inhibition of TrxR is an important clinical goal.
      As a general rule, the affinities and mechanisms of binding of TrxR inhibitors to
      the target enzyme are known with scarce precision and conflicting results abound
      in the literature. A relevant analysis of published results as well as the
      experimental procedures is therefore needed, also in view of the critical
      interest of TrxR inhibitors. We review the inhibitors of TrxR and related
      flavoreductases and the classical treatment of reversible, competitive, non
      competitive and uncompetitive inhibition with respect to TrxR, and in some cases
      we are able to reconcile contradictory results generated by oversimplified data
      analysis. 

PMID- 24875645
TI  - "Qufeng Tongluo" acupuncture prevents the progression of glomerulonephritis by
      decreasing renal sympathetic nerve activity.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Although the exact mechanism(s) underlying
      acupuncture remain unknown, acupuncture and acupuncture-like somatic nerve
      stimulation have been used to treat different kidney diseases and several
      complications related to them.The aim of this preliminary study was to assess the
      effectiveness of acupuncture on glomerulonephritis (GN) according to the theory
      of "Wind-hided renal collaterals" previously proposed. MATERIAL AND METHODS: We
      used a New Zealand white rabbit model of cationized bovine serum albumin (cBSA)
      induced glomerulonephritis and then administered them metoprolol, irbesartan or
      acupuncture to evaluate the effectiveness of acupuncture treatment and
      preliminarily explore its potential mechanism. RESULTS: After immunization, our
      results showed that compared to the cBSA+MET and cBSA+IRB medication groups,
      "Qufeng Tongluo" significantly lowered parameters of renal function and improved
      podocyte injury in the 3rd, 6th and 8th weeks of treatment. Moreover, acupuncture
      increased the protein expression of phosphorylated ERK1/2. CONCLUSIONS: Our study
      suggests that a potential mechanism by which acupuncture has an antihypertensive
      effect and can significantly halt deteriorating renal function due to cBSA GN
      might be mediated by inhibiting the Erk1/2 MAPK pathway to reduce renal
      sympathetic nerve activity (RSNA).

PMID- 24875646
TI  - Effect of the total saponins of Aralia elata (Miq) Seem on cardiac contractile
      function and intracellular calcium cycling regulation.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Total saponins of Aralia elata (Miq) Seem (AS)
      from the Chinese traditional herb Longya Aralia chinensis L. can improve cardiac
      function, although the active mechanism remains poorly understood. The present
      study aimed to determine the direct effect of AS on cardiac function in dogs and
      the effects on Ca2+ transient and contractions in isolated rat cardiomyocytes.
      MATERIAL AND METHODS: In anesthetized dogs, hemodynamic indexes and myocardial
      oxygen consumption were determined before and after AS was administered. In
      isolated adult rat cardiomyocytes, contractile and intracellular Ca2+ properties
      were determined simultaneously in real time by using an IonOptix MyoCam system.
      RESULTS: Our results showed that AS directly induced a positive inotropic effect
      and improved coronary blood flow and energy metabolism, indicating that AS
      induced a beneficial effect to treat myocardial ischemia/reperfusion injury.
      Moreover, AS increased sarcomere shortening, maximal velocity of
      shortening/relengthening (+/-dL/dt), amplitude of [Ca2+]i transients and SERCA
      activity in a concentration-dependent manner. PKCepsilon was also activated after
      the cells were treated with AS. CONCLUSION: These findings revealed the positive
      inotropic effect of AS on canine myocardium and isolated rat cardiomyocytes. This
      effect was possibly associated with an increase in amplitude of the [Ca2+]i
      transient and PKCepsilon-dependent signaling pathway.

PMID- 24875647
TI  - Discovery and functional annotation of SIX6 variants in primary open-angle
      glaucoma.
AB  - Glaucoma is a leading cause of blindness worldwide. Primary open-angle glaucoma
      (POAG) is the most common subtype and is a complex trait with multigenic
      inheritance. Genome-wide association studies have previously identified a
      significant association between POAG and the SIX6 locus (rs10483727, odds ratio
      (OR) = 1.32, p = 3.87*10(-11)). SIX6 plays a role in ocular development and has
      been associated with the morphology of the optic nerve. We sequenced the SIX6
      coding and regulatory regions in 262 POAG cases and 256 controls and identified
      six nonsynonymous coding variants, including five rare and one common variant,
      Asn141His (rs33912345), which was associated significantly with POAG (OR = 1.27,
      p = 4.2*10(-10)) in the NEIGHBOR/GLAUGEN datasets. These variants were tested in
      an in vivo Danio rerio (zebrafish) complementation assay to evaluate ocular
      metrics such as eye size and optic nerve structure. Five variants, found
      primarily in POAG cases, were hypomorphic or null, while the sixth variant, found
      only in controls, was benign. One variant in the SIX6 enhancer increased
      expression of SIX6 and disrupted its regulation. Finally, to our knowledge for
      the first time, we have identified a clinical feature in POAG patients that
      appears to be dependent upon SIX6 genotype: patients who are homozygous for the
      SIX6 risk allele (His141) have a statistically thinner retinal nerve fiber layer
      than patients homozygous for the SIX6 non-risk allele (Asn141). Our results, in
      combination with previous SIX6 work, lead us to hypothesize that SIX6 risk
      variants disrupt the development of the neural retina, leading to a reduced
      number of retinal ganglion cells, thereby increasing the risk of glaucoma
      associated vision loss.

PMID- 24875648
TI  - Use of herbal medicines and natural products: an alternative approach to
      overcoming the apoptotic resistance of pancreatic cancer.
AB  - Pancreatic cancer has a poor prognosis with a 5-year survival rate of <5%. It
      does not respond well to either chemotherapy or radiotherapy, due partly to
      apoptotic resistance (AR) of the cancer cells. AR has been attributed to certain
      genetic abnormalities or defects in apoptotic signaling pathways. In pancreatic
      cancer, significant mutations of K-ras and p53, constitutive activation of
      NFkappaB, over-expression of heat shock proteins (Hsp90, Hsp70), histone
      deacetylase (HDACs) and the activities of other proteins (COX-2, Nrf2 and bcl-2
      family members) are closely linked with resistance to apoptosis and invasion. AR
      has also been associated with aberrant signaling of MAPK, PI3K-AKT, JAK/STAT,
      SHH, Notch, and Wnt/beta-catenin pathways. Strategies targeting these signaling
      molecules and pathways provide an alternative for overcoming AR in pancreatic
      cancer. The use of herbal medicines or natural products (HM/NPs) alone or in
      combination with conventional anti-cancer agents has been shown to produce
      beneficial effects through actions upon multiple molecular pathways involved in
      AR. The current standard first-line chemotherapeutic agents for pancreatic cancer
      are gemcitabine (Gem) or Gem-containing combinations; however, the efficacy is
      dissatisfied and this limitation is largely attributed to AR. Meanwhile, emerging
      data have pointed to a combination of HM/NPs that may augment the sensitivity of
      pancreatic cancer cells to Gem. Greater understanding of how these compounds
      affect the molecular mechanisms of apoptosis may propel development of HM/NPs as
      anti-cancer agents and/or adjuvant therapies forward. In this review, we give a
      critical appraisal of the use of HM/NPs alone and in combination with anti-cancer
      drugs. We also discuss the potential regulatory mechanisms whereby AR is involved
      in these protective pathways. 

PMID- 24875649
TI  - Next generation sequencing reveals microRNA isoforms in liver cirrhosis and
      hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) represents the major histological subtype of liver
      cancer. Tumorigenic changes in hepatic cells potentially result from aberrant
      expression of microRNAs (miRNAs). Individual microRNA gene may give rise to
      miRNAs of different length, named isomiRNAs that proved to be functionally
      relevant. Since microRNA length heterogeneity in hepatic tissue has not been
      described before, we employed next-generation sequencing to comprehensively
      analyze microRNA transcriptome in HCC tumors (n=24) and unaffected tissue
      adjacent to tumors (n=24), including samples with (n=15) and without cirrhosis
      (n=9). We detected 374 microRNAs expressed in liver, including miR-122-5p that
      constituted over 39% of the hepatic miRnome. Among the liver expressed miRs, the
      levels of 64 significantly differed between tumor and control samples (FDR<0.05,
      fold change>2). Top deregulated miRNAs included miR-1269a (T/N=22.95), miR-3144
      3p (T/N=5.24), miR-183-5p (T/N=4.63), miR-10b-5p (T/N=3.87), miR-490-3p
      (T/N=0.13), miR-199a-5p (T/N=0.17), miR-199a-3p/miR-199b-3p (T/N=0.19), miR-214
      5p (T/N=0.20) and miR-214-3p (T/N=0.21). Almost all miRNA genes produced several
      mature molecules differing in length (isomiRNAs). The reference sequence was not
      the most prevalent in 38.6% and completely absent in 10.5% of isomiRNAs. Over
      26.1% of miRNAs produced isoforms carrying>=2 alternative seed regions, of which
      35.5% constituted novel, previously unknown seeds. This fact sheds new light on
      the percentage of the human genome regulated by microRNAs and their variants.
      Among the most deregulated miRNAs, miR-199a-3p/miR-199b-3p (T/N fold change=0.18,
      FDR=0.005) was expressed in 9 isoforms with 3 different seeds, concertedly
      leading to upregulation of TGF-beta signaling pathway (OR=1.99; p=0.004). In
      conclusion, the study reveals the comprehensive miRNome of hepatic tissue and
      provides new tools for investigation of microRNA-dependent pathways in cirrhotic
      liver and hepatocellular carcinoma. This article is part of a Directed Issue
      entitled: Rare Cancers. 

PMID- 24875650
TI  - Biophysical characterization of sites of host adaptive mutation in the influenza
      A virus RNA polymerase PB2 RNA-binding domain.
AB  - Influenza RNA polymerase is composed of three subunits, PA, PB1, and PB2, which
      interact with each other for transcription and replication of the viral RNA
      genome in the nucleus of infected cells. PB2 RNA-binding 627-domain (residues 535
      693), located in the C-terminus, presents a highly basic surface around residue
      lysine 627 and has been proposed to interact with viral or cellular factors,
      resulting in host adaptation. However, the function of this domain is not yet
      characterized in detail. In this study, we identified RNA-binding activity and
      RNA-binding surfaces in both the N-terminal and basic C-terminal regions of PB2
      627-domain using NMR experiments. Through mutagenesis studies, we confirmed which
      residues directly interact with RNA and mapped their locations on the RNA-binding
      surface. In addition, by luciferase activity assays, we showed that influenza
      virus polymerase activity may correlate with the interaction between PB2 and RNA.
      Representative host adaptive mutations (residues 591 and 627) were found to be
      located on the RNA-binding surface and were confirmed to directly interact with
      RNA and to affect polymerase activity. From these results, we suggest that
      influenza virus polymerase activity may be regulated through the interaction
      between PB2 627-domain and RNA and that consequently host adaptation of the virus
      may be influenced. 

PMID- 24875651
TI  - Bosutinib: a third generation tyrosine kinase inhibitor for the treatment of
      chronic myeloid leukemia.
AB  - Bosutinib is an oral tyrosine kinase inhibitor (TKI) with very potent dual
      inhibitory activity against SRC and abelson gene. Bosutinib was approved in 2012
      for the treatment of resistant Philadelphia chromosome positive chronic myeloid
      leukemia (CML). Bosutinib is a very effective TKI against all phases of
      intolerant or resistant CML regardless of the presence or absence of an abelson
      gene domain mutation, except for cases with detectable T315I or V299L. Bosutinib
      is overall well tolerated and associated with a unique, but manageable toxicity
      profile. Factors that influence the prescribing pattern of this drug are complex
      and include physicians', and increasingly patients and families' preference,
      patients' comorbid conditions, schedule of administration, as well as financial
      factors. This paper provides an overview of CML, the TKI market,
      pharmacokinetics, pharmacodynamics, clinical efficacy, safety and tolerability of
      bosutinib. 

PMID- 24875653
TI  - Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic
      review and meta-analysis.
AB  - BACKGROUND: Inflammation may play an important role in cancer progression, and a
      high neutrophil-to-lymphocyte ratio (NLR) has been reported to be a poor
      prognostic indicator in several malignancies. Here we quantify the prognostic
      impact of this biomarker and assess its consistency in solid tumors. METHODS: A
      systematic review of electronic databases was conducted to identify publications
      exploring the association of blood NLR and clinical outcome in solid tumors.
      Overall survival (OS) was the primary outcome, and cancer-specific survival
      (CSS), progression-free survival (PFS), and disease-free survival (DFS) were
      secondary outcomes. Data from studies reporting a hazard ratio and 95% confidence
      interval (CI) or a P value were pooled in a meta-analysis. Pooled hazard ratios
      were computed and weighted using generic inverse-variance and random-effect
      modeling. All statistical tests were two-sided. RESULTS: One hundred studies
      comprising 40559 patients were included in the analysis, 57 of them published in
      2012 or later. Median cutoff for NLR was 4. Overall, NLR greater than the cutoff
      was associated with a hazard ratio for OS of 1.81 (95% CI = 1.67 to 1.97; P <
      .001), an effect observed in all disease subgroups, sites, and stages. Hazard
      ratios for NLR greater than the cutoff for CSS, PFS, and DFS were 1.61, 1.63, and
      2.27, respectively (all P < .001). CONCLUSIONS: A high NLR is associated with an
      adverse OS in many solid tumors. The NLR is a readily available and inexpensive
      biomarker, and its addition to established prognostic scores for clinical
      decision making warrants further investigation.

PMID- 24875654
TI  - Low Resistance Thought Induction Sleep-regulating Technique (TIP3-2) combined
      with medication for primary insomnia: a randomized controlled trial.
AB  - BACKGROUND: Cognitive behavioral therapy for insomnia (CBT-I) is well-validated
      in the western countries. However, it has not been widely adopted or disseminated
      in China. One possibility is that therapeutic approaches drawn from traditional
      Chinese medicine (TCM) will be more widely accepted. PURPOSE: This study aimed to
      evaluate the efficacy of medication in combination with a therapeutic approach
      drawn from TCM, Low Resistance Thought Induction Sleep-regulating Technique (TIP3
      2), for acute treatment of insomnia. METHOD: A randomized controlled trial was
      conducted. Ninety primary insomnia patients were randomly assigned to receive
      TIP3-2 combined with medication (n = 45) or medication only (n = 45) for 4 weeks.
      Medication consisted of 1-2 mg Estazolam nightly. On the basis of taking
      Estazolam, TIP3-2 combined with medication group was given Low Resistance Thought
      Induction Sleep-regulating Technique (TIP3-2) treatment twice a week. Outcomes
      were assessed with the Pittsburgh sleep quality index (PSQI) and polysomnography
      (PSG) before and after treatment. RESULTS: Both groups demonstrated significant
      improvements in the PSQI and polysomnography indices. The TIP3-2+ medication
      group demonstrated a significant difference between the two groups in PSQI total
      score, sleep medication use, daytime dysfunction, subjective sleep quality, as
      well as polysomnography indices of sleep efficiency and awakening times (P <
      0.05). CONCLUSION: Among patients with primary insomnia, the addition of TIP3-2
      provided benefits above and beyond the role of medication alone.

PMID- 24875655
TI  - Tissue surface information for intraoperative incision planning and focus
      adjustment in laser surgery.
AB  - PURPOSE: Introducing computational methods to laser surgery are an emerging
      field. Focusing on endoscopic laser interventions, a novel approach is presented
      to enhance intraoperative incision planning and laser focusing by means of tissue
      surface information obtained by stereoscopic vision. METHODS: Tissue surface is
      estimated with stereo-based methods using nonparametric image transforms.
      Subsequently, laser-to-camera registration is obtained by ablating a pattern on
      tissue substitutes and performing a principle component analysis for precise
      laser axis estimation. Furthermore, a virtual laser view is computed utilizing
      trifocal transfer. Depth-based laser focus adaptation is integrated into a custom
      experimental laser setup in order to achieve optimal ablation morphology.
      Experimental validation is conducted on tissue substitutes and ex vivo animal
      tissue. RESULTS: Laser-to-camera registration gives an error between planning and
      ablation of less than 0.2 mm. As a result, the laser workspace can accurately be
      highlighted within the live views and incision planning can directly be
      performed. Experiments related to laser focus adaptation demonstrate that
      ablation geometry can be kept almost uniform within a depth range of 7.9 mm,
      whereas cutting quality significantly decreases when the laser is defocused.
      CONCLUSIONS: An automatic laser focus adjustment on tissue surfaces based on
      stereoscopic scene information is feasible and has the potential to become an
      effective methodology for optimal ablation. Laser-to-camera registration
      facilitates advanced surgical planning for prospective user interfaces and
      augmented reality extensions.

PMID- 24875657
TI  - Photoelectrochemical hydrogen production on InP nanowire arrays with molybdenum
      sulfide electrocatalysts.
AB  - Semiconductor nanowire arrays are expected to be advantageous for
      photoelectrochemical energy conversion due to their reduced materials
      consumption. In addition, with the nanowire geometry the length scales for light
      absorption and carrier separation are decoupled, which should suppress bulk
      recombination. Here, we use vertically aligned p-type InP nanowire arrays, coated
      with noble-metal-free MoS3 nanoparticles, as the cathode for photoelectrochemical
      hydrogen production from water. We demonstrate a photocathode efficiency of 6.4%
      under Air Mass 1.5G illumination with only 3% of the surface area covered by
      nanowires.

PMID- 24875658
TI  - Copper(II)-catalyzed C-O coupling of aryl bromides with aliphatic diols:
      synthesis of ethers, phenols, and benzo-fused cyclic ethers.
AB  - A highly efficient copper-catalyzed C-O cross-coupling reaction between aryl
      bromides and aliphatic diols has been developed employing a cheaper, more
      efficient, and easily removable copper(II) catalyst. A broad range of aryl
      bromides were coupled with aliphatic diols of different lengths using 5 mol%
      CuCl2 and 3 equivalents of K2CO3 in the absence of any other ligands or solvents
      to afford the corresponding hydroxyalkyl aryl ethers in good to excellent yields.
      In this newly developed protocol, aliphatic diols have multilateral functions as
      coupling reactants, ligands, and solvents. The resulting hydroxyalkyl aryl ethers
      were further readily converted into the corresponding phenols, presenting a
      valuable alternative way to phenols from aryl bromides. Furthermore, it was
      demonstrated that they are useful intermediates for more advanced molecules such
      as benzofurans and benzo-fused cyclic ethers.

PMID- 24875656
TI  - Engineering of hollow mesoporous silica nanoparticles for remarkably enhanced
      tumor active targeting efficacy.
AB  - Hollow mesoporous silica nanoparticle (HMSN) has recently gained increasing
      interests due to their tremendous potential as an attractive nano-platform for
      cancer imaging and therapy. However, possibly due to the lack of efficient in
      vivo targeting strategy and well-developed surface engineering techniques,
      engineering of HMSN for in vivo active tumor targeting, quantitative tumor uptake
      assessment, multimodality imaging, biodistribution and enhanced drug delivery
      have not been achieved to date. Here, we report the in vivo tumor targeted
      positron emission tomography (PET)/near-infrared fluorescence (NIRF) dual
      modality imaging and enhanced drug delivery of HMSN using a generally applicable
      surface engineering technique. Systematic in vitro and in vivo studies have been
      performed to investigate the stability, tumor targeting efficacy and specificity,
      biodistribution and drug delivery capability of well-functionalized HMSN nano
      conjugates. The highest uptake of TRC105 (which binds to CD105 on tumor
      neovasculature) conjugated HMSN in the 4T1 murine breast cancer model was
      ~10%ID/g, 3 times higher than that of the non-targeted group, making surface
      engineered HMSN a highly attractive drug delivery nano-platform for future cancer
      theranostics. 

PMID- 24875659
TI  - Plasma ghrelin concentrations are negatively correlated with urine albumin-to
      creatinine ratio in newly diagnosed type 2 diabetes.
AB  - BACKGROUND: Aging is associated with a decrease in appetite, energy intake and
      glucose tolerance. Experimental studies have suggested that ghrelin and obestatin
      play a role in glucose homeostasis and in the regulation of energy metabolism.
      However, few studies have been performed on the role of ghrelin and obestatin in
      middle-aged and old adults. METHODS: In the present study, we investigated the
      plasma concentrations of ghrelin and obestatin in middle-aged (41-64 years) and
      old (65-76 years) subjects with newly diagnosed type 2 diabetes mellitus (NDD)
      and normal glucose tolerance (NGT). We also characterized the relationship among
      plasma ghrelin and obestatin levels and glucose/lipid metabolism. The fasting
      plasma ghrelin and obestatin concentrations were analyzed using enzyme
      immunoassay method. RESULTS: Plasma obestatin concentrations in diabetic subjects
      were significantly lower than those in NGT subjects. Plasma ghrelin were
      negatively associated with fasting glucose, hemoglobin A1c, urine albumin-to
      creatinine ratio (UACR) and positively correlated with high-density lipoprotein
      cholesterol. In addition, plasma obestatin level was correlated negatively with
      systolic blood pressure, triglycerides and total cholesterol. Furthermore,
      multiple regression analysis indicated that UACR was a significantly independent
      predictor of fasting plasma ghrelin levels. CONCLUSIONS: Collectively, ghrelin
      and obestatin levels may be markers reflecting glucose and lipid conditions in
      NDD. The lower ghrelin levels may be a potential indicator for renal dysfunction
      in patients with type 2 diabetes mellitus.

PMID- 24875660
TI  - Peritoneal dialysis: misperceptions and reality.
AB  - Peritoneal dialysis (PD) continues to be underutilized in the United States, even
      though it is less expensive, provides better quality of life and has better
      outcomes compared with hemodialysis. The reasons for low utilization of PD are
      influenced by complex psychosocial and economic factors, lack of physician
      training, physician bias and inadequate pre-end-stage renal disease care and
      education to the patients. Providing quality pre-end-stage renal disease
      education to patients and families and improving education and training of
      physician in PD, so that they become comfortable with the therapy, are of
      paramount importance to increase PD growth. Minimizing episodes of PD-related
      infections and noninfectious complications, preserving peritoneal membrane using
      more biocompatible solutions and drugs, such as angiotensin-converting enzyme
      inhibitors and angiotensin receptor blockers, and careful management of volume
      status can reduce the loss of PD patients to hemodialysis. Timely surgical
      interventions can prevent the malfunction and loss of PD catheters. Consolidating
      smaller PD facilities in a given geographical area into a single large PD center
      can further improve PD outcomes and PD growth. Finally, with the introduction of
      bundled payment for dialysis services, PD may emerge as a cost-effective therapy
      and rekindle interest in the dialysis community to consider PD as a better renal
      replacement therapy option.

PMID- 24875661
TI  - Why do we not toe the line drawn by the National Institute for Clinical
      Excellence for internal jugular vein cannulation?

PMID- 24875662
TI  - 'Known unknowns and unknown unknowns': electroencephalographic burst suppression
      and mortality.

PMID- 24875664
TI  - Limited destruction of renal nerves after catheter-based renal denervation:
      results of a human case study.
AB  - Renal denervation (RDN) is a promising novel treatment for resistant
      hypertension. Effectiveness of treatment is, however, highly variable and
      unpredictable. Incomplete denervation of the renal nerves is a plausible
      explanation for the variable blood pressure lowering effect of RDN. Here, we
      present for the first time a histopathological evaluation of the effects of RDN
      on perivascular nerves of the renal arteries in a human patient. Our findings
      potentially have important implications for future directions with RDN. 

PMID- 24875663
TI  - Treatment of established left ventricular hypertrophy with fibroblast growth
      factor receptor blockade in an animal model of CKD.
AB  - BACKGROUND: Activation of fibroblast growth factor receptor (FGFR)-dependent
      signalling by FGF23 may contribute to the complex pathogenesis of left
      ventricular hypertrophy (LVH) in chronic kidney disease (CKD). Pan FGFR blockade
      by PD173074 prevented development of LVH in the 5/6 nephrectomy rat model of CKD,
      but its ability to treat and reverse established LVH is unknown. METHODS: CKD was
      induced in rats by 5/6 nephrectomy. Two weeks later, rats began treatment with
      vehicle (0.9% NaCl) or PD173074, 1 mg/kg once-daily for 3 weeks. Renal function
      was determined by urine and blood analyses. Left ventricular (LV) structure and
      function were determined by echocardiography, histopathology, staining for
      myocardial fibrosis (Sirius-Red) and investigating cardiac gene expression
      profiles by real-time PCR. RESULTS: Two weeks after inducing CKD by 5/6
      nephrectomy, rats manifested higher (mean +/- SEM) systolic blood pressure (208
      +/- 4 versus 139 +/- 3 mmHg; P < 0.01), serum FGF23 levels (1023 +/- 225 versus
      199 +/- 9 pg/mL; P < 0.01) and LV mass (292 +/- 9 versus 220 +/- 3 mg; P < 0.01)
      when compared with sham-operated animals. Thereafter, 3 weeks of treatment with
      PD173074 compared with vehicle did not significantly change blood pressure,
      kidney function or metabolic parameters, but significantly reduced LV mass (230
      +/- 14 versus 341 +/- 33 mg; P < 0.01), myocardial fibrosis (2.5 +/- 0.7 versus
      5.4 +/- 0.95% staining/field; P < 0.01) and cardiac expression of genes
      associated with pathological LVH, while significantly increasing ejection
      fraction (18 versus 2.5% post-treatment increase; P < 0.05). CONCLUSIONS: FGFR
      blockade improved cardiac structure and function in 5/6 nephrectomy rats with
      previously established LVH. These data support FGFR activation as a potentially
      modifiable, blood pressure-independent molecular mechanism of LVH in CKD.

PMID- 24875665
TI  - Testing of a femtosecond pulse laser in outer space.
AB  - We report a test operation of an Er-doped fibre femtosecond laser which was
      conducted for the first time in outer space. The fibre-based ultrashort pulse
      laser payload was designed to meet space-use requirements, undergone through
      ground qualification tests and finally launched into a low-earth orbit early in
      2013. Test results obtained during a one-year mission lifetime confirmed stable
      mode-locking all the way through although the radiation induced attenuation (RIA)
      in the Er-doped gain fibre caused an 8.6% reduction in the output power. This
      successful test operation would help facilitate diverse scientific and
      technological applications of femtosecond lasers in space and earth atmosphere in
      the near future. 

PMID- 24875666
TI  - Evaluation of dried blood spot collection paper blotters for avian sexing by
      direct PCR.
AB  - Abstract 1. Avian sexing by polymerase chain reaction (PCR) plays an important
      role in sexual identification of avian species with similar phenotypes. Dried
      blood spots (DBSs) on paper blotters can help reduce the cost and problem of
      sample transportation and processing. 2. In the first experiment, several kinds
      of papers were evaluated for collecting DBS for chicken sexing by direct PCR with
      different processing methods. The most practical method with cost optimality was
      the utilisation of Whatman grade 1 filter paper with the combination of methanol
      fixation and boiling. 3. A second experiment was performed to determine whether
      cross-contamination could occur among samples cut with the same scissors. No
      clean scissors were compared with ones cleaned with bleach-ethanol combination or
      0.3N HCl. The PCR results showed that all three methods provided correct amplicon
      sizes without any false-positives regardless of the utilisation of cleaning
      intervention. 4. In conclusion, a technique that is suitable for DBS collection
      for avian sexing by direct PCR with cost efficacy was developed, and it was also
      shown that the utilisation of the same pair of scissors for several DBS samples
      did not affect the PCR results. 

PMID- 24875667
TI  - Mining novel effector proteins from the esophageal gland cells of Meloidogyne
      incognita.
AB  - Meloidogyne incognita is one of the most economically damaging plant pathogens in
      agriculture and horticulture. Identifying and characterizing the effector
      proteins which M. incognita secretes into its host plants during infection is an
      important step toward finding new ways to manage this pest. In this study, we
      have identified the cDNAs for 18 putative effectors (i.e., proteins that have the
      potential to facilitate M. incognita parasitism of host plants). These putative
      effectors are secretory proteins that do not contain transmembrane domains and
      whose genes are specifically expressed in the secretory gland cells of the
      nematode, indicating that they are likely secreted from the nematode through its
      stylet. We have determined that, in the plant cells, these putative effectors are
      likely to localize to the cytoplasm. Furthermore, the transcripts of many of
      these novel effectors are specifically upregulated during different stages of the
      nematode's life cycle, indicating that they function at specific stages during M.
      incognita parasitism. The predicted proteins showed little to no homology to
      known proteins from free-living nematode species, suggesting that they evolved
      recently to support the parasitic lifestyle. On the other hand, several of the
      effectors are part of gene families within the M. incognita genome as well as
      that of M. hapla, which points to an important role that these putative effectors
      are playing in both parasites. With the discovery of these putative effectors, we
      have increased our knowledge of the effector repertoire utilized by root-knot
      nematodes to infect, feed on, and reproduce on their host plants. Future studies
      investigating the roles that these proteins play in planta will help mitigate the
      effects of this damaging pest. 

PMID- 24875669
TI  - A comparative study on the effects of pristine and functionalized single-walled
      carbon nanotubes on osteoblasts: ultrastructural and biochemical properties.
AB  - A comparative study was performed to investigate the ultrastructural and
      biomolecular properties of osteoblasts induced by three types of single-walled
      carbon nanotubes (SWNTs). The results on cellular uptake and ultrastructural
      alteration indicate that SWNTs enter osteoblasts by endocytosis. SWNTs-COOH and
      SWNTs-OH particles were freely dispersed in the cytoplasm, while pristine SWNTs
      were localized to the periphery of the cell. Both SWNTs-OH and SWNTs-COOH
      promoted cell changes in cell activity regarding mRNA expression at doses of 50
      and 100 MUg/mL in the first 24 h. When treated with 50 MUg/mL SWNTs-COOH for 48
      h, the expression of type I collagen increased by 6.3-fold (for MG63) or 9.1-fold
      (for primary osteoblasts) compared with the control group. The present study
      observed for the first time that SWNTs-COOH initiated the prompt and the maximum
      upregulation of type I collagen gene expression, and simultaneously induced the
      expansion of the endoplasmic reticulum for increased protein synthesis, which in
      turn accelerated the mineralization process. However, impaired cell properties
      and mitochondrial injury were detected following treatment with SWNTs at 100
      MUg/mL after 48 h. In conclusion, we believe that SWNTs-COOH is a good candidate
      for the fabrication of biomedical scaffolds for bone regeneration. 

PMID- 24875668
TI  - Research updates in neuroimaging studies of children who stutter.
AB  - In the past two decades, neuroimaging investigations of stuttering have led to
      important discoveries of structural and functional brain differences in people
      who stutter, providing significant clues to the neurological basis of stuttering.
      One major limitation, however, has been that most studies so far have only
      examined adults who stutter, whose brain and behavior likely would have adopted
      compensatory reactions to their stuttering; these confounding factors have made
      interpretations of the findings difficult. Developmental stuttering is a
      neurodevelopmental condition, and like many other neurodevelopmental disorders,
      stuttering is associated with an early childhood onset of symptoms and greater
      incidence in males relative to females. More recent studies have begun to examine
      children who stutter using various neuroimaging techniques that allow examination
      of functional neuroanatomy and interaction of major brain areas that
      differentiate children who stutter compared with age-matched controls. In this
      article, I review these more recent neuroimaging investigations of children who
      stutter, in the context of what we know about typical brain development,
      neuroplasticity, and sex differences relevant to speech and language development.
      Although the picture is still far from complete, these studies have potential to
      provide information that can be used as early objective markers, or prognostic
      indicators, for persistent stuttering in the future. Furthermore, these studies
      are the first steps in finding potential neural targets for novel therapies that
      may involve modulating neuroplastic growth conducive to developing and
      maintaining fluent speech, which can be applied to treatment of young children
      who stutter. 

PMID- 24875671
TI  - Effect of high potassium diet on endothelial function.
AB  - BACKGROUND AND AIMS: Increased potassium intake is related to reduced blood
      pressure (BP) and reduced stroke rate. The effect of increased dietary potassium
      on endothelial function remains unknown. The aim was to determine the effect of
      increased dietary potassium from fruit and vegetables on endothelial function.
      METHODS AND RESULTS: Thirty five healthy men and women (age 32 +/- 12 y)
      successfully completed a randomised cross-over study of 2 * 6 day diets either
      high or low in potassium. Flow mediated dilatation (FMD), BP, pulse wave velocity
      (PWV), augmentation index (AI) and a fasting blood sample for analysis of
      Intercellular Adhesion Molecule-1 (ICAM-1), E-selectin, asymmetric
      dimethylarginine (ADMA) and endothelin-1 were taken on completion of each
      intervention. Dietary change was achieved by including bananas and potatoes in
      the high potassium and apples and rice/pasta in the low potassium diet. Dietary
      adherence was assessed using 6 day weighed food diaries and a 24 h urine sample.
      The difference in potassium excretion between the two diets was 48 +/- 32 mmol/d
      (P = 0.000). Fasting FMD was significantly improved by 0.6% +/- 1.5% following
      the high compared to the low potassium diet (P = 0.03). There were no significant
      differences in BP, PWV, AI, ICAM-1, ADMA or endothelin-1 between the
      interventions. There was a significant reduction in E-selectin following the high
      (Median = 5.96 ng/ml) vs the low potassium diet (Median = 6.24 ng/ml), z = -2.49,
      P = 0.013. CONCLUSION: Increased dietary potassium from fruit and vegetables
      improves FMD within 1 week in healthy men and women but the mechanisms for this
      effect remain unclear. CLINICAL TRIAL REGISTRY: ACTRN12612000822886.

PMID- 24875670
TI  - Breaking up prolonged sitting reduces resting blood pressure in overweight/obese
      adults.
AB  - AIM: To compare the effect of 7 h of prolonged sitting on resting blood pressure
      with a similar duration of sitting combined with intermittent brief bouts of
      light-intensity or moderate-intensity physical activity. METHODS AND RESULTS:
      Overweight/obese adults (n = 19; aged 45-65 years) were recruited for a
      randomized three-treatment crossover trial with a one-week washout between
      treatments: 1) uninterrupted sitting; 2) sitting with 2 min bouts of light
      intensity walking at 3.2 km/h every 20 min; and, 3) sitting with 2 min bouts of
      moderate-intensity walking at between 5.8 and 6.4 km/h every 20 min. After an
      initial 2 h period seated, participants consumed a test meal (75 g carbohydrate,
      50 g fat) and completed each condition over the next 5 h. Resting blood pressure
      was assessed oscillometrically every hour as a single measurement, 5 min prior to
      each activity bout. GEE models were adjusted for sex, age, BMI, fasting blood
      pressure and treatment order. After adjustment for potential confounding
      variables, breaking up prolonged sitting with light and moderate-intensity
      activity breaks was associated with lower systolic blood pressure [light: 120 +/-
      1 mmHg (estimated marginal mean +/- SEM), P = 0.002; moderate: 121 +/- 1 mmHg, P
      = 0.02], compared to uninterrupted sitting (123 +/- 1 mmHg). Diastolic blood
      pressure was also significantly lower during both of the activity conditions
      (light: 76 +/- 1 mmHg, P = 0.006; moderate: 77 +/- 1 mmHg, P = 0.03) compared to
      uninterrupted sitting (79 +/- 1 mmHg). No significant between-condition
      differences were observed in mean arterial pressure or heart rate. CONCLUSION:
      Regularly breaking up prolonged sitting may reduce systolic and diastolic blood
      pressure. TRIAL REGISTRATION NUMBER: ACTRN12609000656235
      (http://www.anzctr.org.au) TRIAL REGISTRATION DATE: August 4th 2009.

PMID- 24875673
TI  - Sleep time during adolescence and risk of overweight: an implausible
      relationship.

PMID- 24875675
TI  - The mechanism of catalytic methylation of 2-phenylpyridine using di-tert-butyl
      peroxide.
AB  - The mechanism of palladium chloride-catalyzed direct methylation of arenes with
      peroxides is elucidated by using the energetics computed at the M06 density
      functional theory. The introduction of a methyl group by tert-butyl peroxides at
      the ortho-position of a prototypical 2-phenyl pyridine, a commonly used substrate
      in directed C-H functionalization reactions, is examined in detail by identifying
      the key intermediates and transition states involved in the reaction sequence.
      Different possibilities that differ in terms of the site of catalyst coordination
      with the substrate and the ensuing mechanism are presented. The important
      mechanistic events involved are (a) an oxidative or a homolytic cleavage of the
      peroxide O-O bond, (b) C-H bond activation, (c) C-C bond activation, and (d)
      reductive elimination involving methyl transfer to the aromatic ring. We have
      examined both radical and non-radical pathways. In the non-radical pathway, the
      lowest energy pathway involves C-H bond activation prior to the coordination of
      the peroxide to palladium, which is subsequently followed by the O-O bond
      cleavage of the peroxide and the C-C bond activation. Reductive elimination in
      the resulting intermediate leads to the vital C-C bond formation between methyl
      and aryl carbon atoms. In the non-radical pathway, the C-C bond activation is
      higher in energy and has been identified as the rate-limiting step of this
      reaction. In the radical pathway, however, the activation barrier for the C-C
      bond cleavage is lower than for the peroxide O-O bond cleavage. A combination of
      a radical pathway up to the formation of a palladium methyl intermediate and a
      subsequent non-radical pathway has been identified as the most favored pathway
      for the title reaction. The predicted mechanism is in good agreement with the
      experimental observations on PdCl2 catalyzed methylation of 2-phenyl pyridine
      using tert-butyl peroxide. 

PMID- 24875674
TI  - Results from the first 12 months of the national surveillance of healthcare
      associated outbreaks in Germany, 2011/2012.
AB  - BACKGROUND: In August 2011, the German Protection against Infection Act was
      amended, mandating the reporting of healthcare associated infection (HAI)
      outbreak notifications by all healthcare workers in Germany via local public
      health authorities and federal states to the Robert Koch Institute (RKI).
      OBJECTIVE: To describe the reported HAI-outbreaks and the surveillance system's
      structure and capabilities. METHODS: Information on each outbreak was collected
      using standard paper forms and notified to RKI. Notifications were screened daily
      and regularly analysed. RESULTS: Between November 2011 and November 2012, 1,326
      paper forms notified 578 HAI-outbreaks, between 7 and 116 outbreaks per month.
      The main causative agent was norovirus (n = 414/578; 72%). Among the 108
      outbreaks caused by bacteria, the most frequent pathogens were Clostridium
      difficile (25%) Klebsiella spp. (19%) and Staphylococcus spp. (19%). Multidrug
      resistant bacteria were responsible for 54/108 (50%) bacterial outbreaks.
      Hospitals were affected most frequently (485/578; 84%). Hospital outbreaks due to
      bacteria were mostly reported from intensive care units (ICUs) (45%), followed by
      internal medicine wards (16%). CONCLUSION: The mandatory HAI-outbreak
      surveillance system describes common outbreaks. Pathogens with a particular high
      potential to cause large or severe outbreaks may be identified, enabling us to
      further focus research and preventive measures. Increasing the sensitivity and
      reliability of the data collection further will facilitate identification of
      outbreaks able to increase in size and severity, and guide specific control
      measures to interrupt their propagation.

PMID- 24875676
TI  - A truncated [Mn(III)12] tetrahedron from oxime-based [Mn(III)3O] building blocks.
AB  - The use of the novel pro-ligand H4L combining the complimentary phenolic oxime
      and diethanolamine moieties in one organic framework, results in the formation of
      the first example of a [Mn(III)12] truncated tetrahedron and an extremely rare
      example of a Mn cage conforming to an Archimedean solid. 

PMID- 24875672
TI  - Dietary isoflavone intake is associated with evoked responses to inflammatory
      cardiometabolic stimuli and improved glucose homeostasis in healthy volunteers.
AB  - BACKGROUND AND AIMS: Consumption of foods that modulate inflammatory stress in
      genetically-prone individuals may influence development of cardiometabolic
      diseases. Isoflavones in soy-derived foods function as phytoestrogens, have
      antioxidant and anti-inflammatory activity, inhibit protein-tyrosine kinase
      activity, and may be atheroprotective. We examined the relationship between soy
      food consumption and inflammatory responses to endotoxemia, postprandial
      responses to oral lipid tolerance test (OLTT), and insulin sensitivity from
      frequently sampled intravenous tolerance tests (FSIGTT). METHODS AND RESULTS: We
      administered low-dose endotoxin (LPS 1 ng/kg) to induce transient endotoxemia in
      young, healthy volunteers (N = 215) of African (AA), and European (EA) ancestry
      as part of the GENE Study. We further supported these findings in two independent
      samples: the MECHE Study and NHANES. Soy food consumption was a significant
      predictor of peak cytokine response following LPS. Individuals with moderate-high
      (>1.48 mg/day, N = 65) vs. low-no (<1.48 mg/day, N = 150) isoflavone consumption
      had significantly higher tumor necrosis factor alpha (TNFalpha) post-LPS (AUC, P
      = 0.009). Further, high-isoflavone consumers were protected against inflammation
      induced decline in insulin sensitivity (SI) in GENE. We observed significant
      differences by soy consumption in the interferon gamma (IFNgamma) response to
      OLTT, and the insulin response to OGTT in MECHE, as well as significantly lower
      fasting insulin, and 2-hour glucose post-OGTT in EA NHANES subjects. CONCLUSION:
      We demonstrate that soy consumption may influence inflammatory and metabolic
      responses. In research of nutritional exposures, measuring evoked phenotypes may
      be more informative than describing resting characteristics. The GENE Study was
      registered under NCT00953667 and the MECHE Study under NCT01172951, both at
      clinicaltrials.gov.

PMID- 24875679
TI  - Section I. Editorial.

PMID- 24875677
TI  - KCNH2 polymorphism and methadone dosage interact to enhance QT duration.
AB  - BACKGROUND: Many drugs increase the duration of the QT interval of patients,
      potentially leading to harmful effects such as polymorphic ventricular
      arrhythmias. Most of these drugs do so by inhibiting the rapid component IKr of
      the delayed rectifier potassium current IK. Methadone is the most prescribed
      heroin maintenance treatment and is known to inhibit the cardiac potassium
      channel hERG, which recapitulates IKr. In order to evaluate if any polymorphism
      of potassium channels' genes could explain some of the "idiosyncratic" QT
      prolongations observed in patients treated with methadone, we tested the
      association between KCNE1, KCNE2, and KCNH2 polymorphism and the QT interval
      prolongation in those patients, controlling for other variables associated with a
      decrease of the repolarizing reserve. METHODS: A cohort of 82 patients treated
      with stable dosage of methadone (mean dosage 65 mg/d) for at least three months
      was genotyped for five polymorphisms in KCNE1, KCNE2 and KCNH2 genes and had
      their corrected QT (QTc) assessed. RESULTS: The mean QTc interval was 415+/-34ms.
      In a linear regression model, longer QTc interval was associated with methadone
      dosage and with one genetic factor. Each copy of a Lys allele at codon 897 of
      KCNH2, the gene that encodes the cardiac potassium voltage-gated channel hERG,
      was associated with a 15.4ms longer QTc (95% CI [4.6-26.2]; p=0.001). CONCLUSION:
      KCNH2 genotyping may be relevant in the analysis of cumulative risk factors for
      QT prolongation in patients on methadone maintenance treatment.

PMID- 24875678
TI  - The nonmedical use of prescription medicines among high school students: a cross
      sectional study in Southern China.
AB  - OBJECTIVES: The objective of this study was to examine the prevalence of the
      nonmedical use of prescription medicines (NMUPM) and the association between
      NMUPM and demographic, family and school factors. METHODS: A cross-sectional
      study was conducted from 2007 to 2009. A total of 21,672 middle and high school
      students were surveyed in seven cities of Guangdong Province. Self-reported NMUPM
      and information regarding family and school factors were collected. Multilevel
      logistic regression analyses were used to explore potentially influential
      factors. RESULTS: Of the total sample, the mean age was 16 (+/-1.9) years.
      Approximately 6.0% of respondents reported lifetime NMUPM. The most common
      nonmedically used prescription drug among NMUPM users was scattered analgesics,
      at approximately 3.9%, followed by cough medicine with codeine (2.1%). Multilevel
      logistic regression analysis indicated that living arrangements, available money,
      social friends, and smoking were significantly correlated with NMUPM among boys
      and girls. Academic achievement and family relationships were only significantly
      correlated with NMUPM among girls, and communication with parents was only
      associated with NMUPM among boys. CONCLUSIONS: These results indicate that NMUPM
      represented a considerable problem for particular subgroups of adolescents. A
      well-established surveillance system and target intervention programs are needed
      given the potential long-term negative outcomes of NMUPM.

PMID- 24875680
TI  - Positive change: connecting the virtual and the real.
AB  - How do we lastingly change our lives for the better? There is not an easy answer
      to this question. However, due to the advances in psychology and neuroscience,
      now we have a better view of personal change, that is not limited to a specific
      viewpoint. In particular, the emergence of integrative and transdiagnostic
      accounts suggests that change is contextual, depending on the person, the issues,
      and the situation. More, personal change is a process, happening in discontinuous
      and nonlinear ways, following life transitions and traumatic events. In this
      process a key role can be played by technology: using the "Positive Technology"
      approach it is possible to use technology to manipulate the quality of
      experience, with the goal of increasing wellness, and generating strengths and
      resilience in individuals, organizations and society. 

PMID- 24875681
TI  - Section II. Critical Reviews.

PMID- 24875683
TI  - Section III. Evaluation Studies.

PMID- 24875682
TI  - Enabling eHealth as a Pathway for Patient Engagement: a Toolkit for Medical
      Practice.
AB  - Academic and managerial interest in patient engagement is rapidly earning
      attention and becoming a necessary tool for researchers, clinicians and
      policymakers worldwide to manage the increasing burden of chronic conditions. The
      concept of patient engagement calls for a reframe of healthcare organizations'
      models and approaches to care. This also requires innovations in the direction of
      facilitating the exchanges between the patients and the healthcare. eHealth,
      namely the use of new communication technologies to provide healthcare, is proved
      to be proposable to innovate healthcare organizations and to improve exchanges
      between patients and health providers. However, little attention has been still
      devoted to how to best design eHealth tools in order to engage patients in their
      care. eHealth tools have to be appropriately designed according to the specific
      patients' unmet needs and priorities featuring the different phases of the
      engagement process. Basing on the Patient Engagement model and on the Positive
      Technology paradigm, we suggest a toolkit of phase-specific technological
      resources, highlighting their specific potentialities in fostering the patient
      engagement process. 

PMID- 24875684
TI  - Positive technology: a free mobile platform for the self-management of
      psychological stress.
AB  - We describe the main features and preliminary evaluation of Positive Technology,
      a free mobile platform for the self-management of psychological stress
      (http://positiveapp.info/). The mobile platform features three main components:
      (i) guided relaxation, which provides the user with the opportunity of browsing a
      gallery of relaxation music and video-narrative resources for reducing stress;
      (ii) 3D biofeedback, which helps the user learning to control his/her responses,
      by visualizing variations of heart rate in an engaging 3D environment; (iii)
      stress tracking, by the recording of heart rate and self-reports. We evaluated
      the Positive Technology app in an online trial involving 32 participants, out of
      which 7 used the application in combination with the wrist sensor. Overall,
      feedback from users was satisfactory and the analysis of data collected online
      indicated the capability of the app for reducing perceived stress levels. A
      future goal is to improve the usability of the application and include more
      advanced stress monitoring features, based on the analysis of heart rate
      variability indexes. 

PMID- 24875685
TI  - Virtual humans and formative assessment to train diagnostic skills in bulimia
      nervosa.
AB  - Carrying out a diagnostic interview requires skills that need to be taught in a
      controlled environment. Virtual Reality (VR) environments are increasingly used
      in the training of professionals, as they offer the most realistic alternative
      while not requiring students to face situations for which they are yet
      unprepared. The results of the training of diagnostic skills can also be
      generalized to any other situation in which effective communication skills play a
      major role. Our aim with this study has been to develop a procedure of formative
      assessment in order to increment the effectiveness of virtual learning simulation
      systems and then to assess their efficacy. 

PMID- 24875686
TI  - A personal health information toolkit for health intervention research.
AB  - With the emergence of mobile health (mHealth) apps, there is a growing demand for
      better tools for developing and evaluating mobile health interventions. Recently
      we developed the Personal Health Intervention Toolkit (PHIT), a software
      framework which eases app implementation and facilitates scientific evaluation.
      PHIT integrates self-report and physiological sensor instruments, evidence-based
      advisor logic, and self-help interventions such as meditation, health education,
      and cognitive behavior change. PHIT can be used to facilitate research,
      interventions for chronic diseases, risky behaviors, sleep, medication adherence,
      environmental monitoring, momentary data collection health screening, and
      clinical decision support. In a series of usability evaluations, participants
      reported an overall usability score of 4.5 on a 1-5 Likert scale and an 85 score
      on the System Usability Scale, indicating a high percentile rank of 95%. 

PMID- 24875687
TI  - Cognitive Assessment of OCD Patients: NeuroVR vs Neuropsychological Test.
AB  - This study aimed to evaluate the reliability and validity of the Neuro-Virtual
      Reality as tool for the neuropsychological assessment in OCD patients. We used
      the neuropsychological battery and a virtual version of the Multiple Errand Test
      (V-MET), developed using the NeuroVR software, in order to evaluate the executive
      functions, the ability to plan ahead on complex problem solving tasks in daily
      life in 30 obsessive compulsive disorder (OCD) patients and 30 healthy controls.
      The results showed the presence of difficulties of OCD patients: lower levels of
      divided attention and higher levels of errors; higher mean rank of
      inefficiencies, interpretation failures and rule breaks and longer time of
      execution of the whole task. By contrast, controls have higher level of
      efficiency and better performance. In addition, a significant correlation was
      found between the V-MET and the neuropsychological battery which confirms and
      supports the ecological validity of neurocognitive assessment through
      NeuroVirtual Reality. 

PMID- 24875688
TI  - A (Cyber)place For Wellbeing: Managing Interactions in eHealth.
AB  - Yukendu is a personal mobile coaching service that supports people in reaching
      good levels of psychological and physical wellbeing through the use of an app and
      a relationship with a health coach. Presenting Yukendu's app functioning, this
      paper aims not only to show that by means of web 2.0 tools is possible to manage
      in a functional way effective eHealth coaching interactions, but also that
      relationships between a coach and a coachee managed in such a way give birth to
      what we could call a 'cyber-wellbeing-place'. 

PMID- 24875689
TI  - Simulated job interview improves skills for adults with serious mental illnesses.
AB  - Adults with serious mental illnesses (e.g., Autism Spectrum Disorder [ASD],
      schizophrenia, post-traumatic stress disorder [PTSD]) often have difficulties
      obtaining employment. The Job Interview Training System with Molly Porter,
      developed in collaboration with Yale and Northwestern Universities and vocational
      rehabilitation specialists with funding from The National Institutes of Health
      (R43/44MH080496), allows learners to practice job interviews on computers in a
      stress free environment. The system includes user-driven educational materials,
      an interactive job application, a practice simulation with a fictional
      interviewer (Molly Porter), and extensive feedback. SIMmersion's PeopleSIMTM
      technology allows each conversation with Molly to provide a unique interview
      experience, enabling users to gain confidence while building skills. The on
      screen coach provides insight during the conversation, and a comprehensive after
      action review provides learners with feedback on the entire interview. In a
      randomized control trial, the system was proven effective at improving
      participants' interview skills and confidence. Ninety-six (96) unemployed adults
      with ASD (n=26), schizophrenia/other (n=37) or PTSD (n=33) were recruited.
      Participants were randomized into control (n=32) and experimental (n=64)
      conditions. The control group was "wait-listed" to receive training, and the
      experimental group used the training system with Molly Porter. Both groups
      completed pre- and post-intervention role-play interviews and self-assessment
      questionnaires. Analyses of covariance showed that the simulation provided a
      highly significant training effect, with experimental group participants scoring
      better in the role-play interviews and self-assessing higher than control group
      participants. By increasing skills and confidence, this system may ultimately
      reduce the length of unemployment for adults with mental illnesses. 

PMID- 24875690
TI  - Controlling a stream of paranoia evoking events in a virtual reality environment.
AB  - Although virtual reality exposure has been reported as a method to induce
      paranoid thought, little is known about mechanisms to control specific virtual
      stressors. This paper reports on a study that examines the effect of controlling
      the stream of potential paranoia evoking events in a virtual restaurant world. A
      2-by-2 experiment with a non-clinical group (n = 24) was conducted with as two
      within-subject factors: (1) the cycle time (short/long) for when the computer
      considers activation of a paranoia evoking event and (2) the probability that a
      paranoia-evoking event (low/high) would be triggered at the completion of a
      cycle. The results showed a significant main effect for the probability factor
      and two-way interaction effect with the cycle time factor on the number of
      paranoid comments participants made and their self-reported anxiety. 

PMID- 24875691
TI  - Compelling Evidence that Exposure Therapy for PTSD Normalizes Brain Function.
AB  - Functional magnetic resonance imaging (fMRI) is helping us better understand the
      neurologic pathways involved in posttraumatic stress disorder (PTSD). We
      previously reported that military service members with PTSD after deployment to
      Iraq or Afghanistan demonstrated significant improvement, or normalization, in
      the fMRI-measured activation of the amygdala, prefrontal cortex and anterior
      cingulate gyrus following exposure therapy for PTSD. However, our original study
      design did not include repeat scans of control participants, rendering it
      difficult to discern how much of the observed normalization in brain activity is
      attributable to treatment, rather than merely a practice effect. Using the same
      Affective Stroop task paradigm, we now report on a larger sample of PTSD-positive
      combat veterans that we treated with exposure therapy, as well as a combat
      exposed control group of service members who completed repeat scans at 3-4 month
      intervals. Findings from the treatment group are similar to our prior report.
      Combat controls showed no significant change on repeat scanning, indicating that
      the observed differences in the intervention group were in fact due to treatment.
      We continue to scan additional study participants, in order to determine whether
      virtual reality exposure therapy has a different impact on regional brain
      activation than other therapies for PTSD. 

PMID- 24875692
TI  - Effects of simulation fidelity on user experience in virtual fear of public
      speaking training - an experimental study.
AB  - Realistic models in virtual reality training applications are considered to
      positively influence presence and performance. The experimental study presented,
      analyzed the effect of simulation fidelity (static vs. animated audience) on
      presence as a prerequisite for performance in a prototype virtual fear of public
      speaking application with a sample of N = 40 academic non-phobic users. Contrary
      to the state of research, no influence was shown on virtual presence and
      perceived realism, but an animated audience led to significantly higher effects
      in anxiety during giving a talk. Although these findings could be explained by an
      application that might not have been realistic enough, they still question the
      role of presence as a mediating factor in virtual exposure applications. 

PMID- 24875694
TI  - Section IV. Original Research.

PMID- 24875695
TI  - The mediating role of facebook fan pages.
AB  - Using the dual mediation hypothesis, this study investigates the role of
      interestingness (the power of attracting or holding one's attention) attitude
      towards the news, in the formation of Facebook Fan Page users' electronic word-of
      mouth intentions. A total of 599 Facebook fan page users in Taiwan were recruited
      and structural equation modeling (SEM) was used to test the research hypotheses.
      The results show that both perceived news entertainment and informativeness
      positively influence interestingness attitude towards the news. Interestingness
      attitude towards the news subsequently influences hedonism and utilitarianism
      attitudes towards the Fan Page, which then influence eWOM intentions.
      Interestingness attitude towards the news plays a more important role than
      hedonism and utilitarianism attitudes in generating electronic word-of-mouth
      intentions. Based on the findings, the implications and future research
      suggestions are provided. 

PMID- 24875693
TI  - Development of a VR Application for Binge Eating Treatment: Identification of
      Contexts and Cues Related to Bingeing Behavior in Spanish Italian Patients.
AB  - The objective of this study was to identify frequent situations and specific cues
      that produce the craving to binge in Spanish and Italian samples of patients with
      eating disorders (ED). There were two main aims: to assess transcultural
      differences in the contexts and cues that elicit food craving; and to develop
      valid, reliable VR environments for effective cue-exposure therapy (CET) for
      patients from both countries. Twenty-six Spanish and 75 Italian ED patients
      completed an ad hoc questionnaire to assess contexts and cues that trigger the
      craving to binge. No differences between groups were found. All patients reported
      experiencing higher levels of craving in the afternoon/early evening and in the
      late evening/night, between meals, when alone, and more frequently at the end of
      the week. Being in the dining room, the kitchen, the bedroom, the bakery and the
      supermarket were the specific situations that produced the highest levels of
      craving to binge. We used the questionnaire results to develop a virtual reality
      application for CET. 

PMID- 24875696
TI  - Marketing analysis of a positive technology app for the self-management of
      psychological stress.
AB  - The INTERSTRESS project developed a completely new concept in the treatment of
      psychological stress: Interreality, a concept that combines cognitive behavioral
      therapy with a hybrid, closed-loop empowering experience bridging real and
      virtual worlds. This model provides the opportunity for individual citizens to
      become active participants in their own health and well-being. This article
      contains the results of the Marketing Trial and analysis of the opinions of
      individual consumers/end users of the INTERSTRESS product. The specific objective
      of this study was to evaluate the feasibility, efficacy and user acceptance of a
      novel mobile-based relaxation training tool in combination with biofeedback
      exercises and wearable biosensors. Relaxation was aided through immersion in a
      mobile virtual scenario (a virtual island) featuring pre-recorded audio
      narratives guiding a series of relaxation exercises. During biofeedback
      exercises, a wearable biosensor system provided data which directly modified the
      virtual reality experience in real-time. Thirty-six participants evaluated the
      product and overall feedback from users was positive, with some variation seen
      based on participant gender. A larger market study is now underway to understand
      if there are cultural variations in acceptability of the device. 

PMID- 24875697
TI  - VR Mobile Solutions For Chronic Stress Reduction in Young Adults.
AB  - Chronic stress in young adults has become a growing problem within recent decades
      and many are unable to find cost-effective and accessible treatment for
      psychological stress in their daily lives. We analyze the market of using a
      mobile application, Positive Technology, as a solution. Eleven participants, aged
      between 18 and 24, participated in the exercise. Self-reported stress reduction
      was measured via an online marketing survey, while physiological measurements
      were monitored via peripheral devices. Secondary goals assessed the app's ease-of
      use, accessibility, and cost. Results indicate that participants enjoyed the
      availability of the mobile solution and found the app to be fun and easy to
      learn. Stress levels were reduced in 73% of the participants, with higher effects
      in females and in participants aged 18-24. We conclude that the mobile platform
      is an effective means of delivering psychological stress reduction, and could
      provide an accessible, cost-effective solution. 

PMID- 24875698
TI  - Quantifying the effectiveness of virtual reality pain management: a pilot study.
AB  - Sensory pathways, consisting of chains of neurons, which spread from the receptor
      organ to the cerebral cortex, are responsible for the perception of sensations
      (including pain). In this study, we set out to determine how effective virtual
      reality (VR) could be in distracting patients from pain experienced through
      thermoreceptors on the skin. Six healthy subjects were exposed to uncomfortable
      pain stimuli with and without VR distraction. Subjects reported a drop in pain
      while in the VR environment, and mean pain rating was significantly lower than
      the session with no VR distraction. These results indicate that VR distraction
      can diminish pain experienced by subjects, thus we conclude by eliciting future
      directions for quantifying effectiveness of VR as a pain management solution. 

PMID- 24875699
TI  - Parental mediation and cyberbullying - a longitudinal study.
AB  - Parents use active and restrictive mediation strategies to guide and regulate
      children's online participation and the online risks they encounter. However,
      changes in parental mediation do occur over time and the effectiveness of these
      strategies on cyberbullying demands for further empirical investigation. The
      current study addresses these issues with a sample of 1084 students (49% girls)
      in a longitudinal, three-wave design. Gender differences were tested via multi
      group analyses. Longitudinal growth models showed that parental use of both
      active and restrictive mediation decreased over time. For both types of
      mediation, the mean rate of change had a significant effect on boys' engagement
      in cyberbullying, but not for girls. Initial levels of restrictive mediation, but
      not active mediation, were found to be significantly predictive of cyberbullying
      in both genders. Girls had higher initial levels of both parental mediation types
      in comparison to boys. The results reveal that the effectiveness of active and
      restrictive mediation in relation to students' cyberbullying differs and informs
      us on gender differences. The implications of these results for parental
      education in online mediation are discussed. 

PMID- 24875700
TI  - Cognitive assessment of stroke patients with mobile apps: a controlled study.
AB  - Stroke is a major cause of cognitive impairments. New technologies such as
      virtual reality and mobile apps have opened up new possibilities of
      neuropsychological assessment and intervention. This paper reports a controlled
      study assessing cognitive functioning through a mobile virtual reality
      application. Fifteen stroke patients recruited from a rehabilitation hospital and
      15 healthy control subjects underwent neuropsychological evaluation with
      traditional paper-and-pencil tests as well as with a pilot version of the
      Systemic Lisbon Battery (SLB). The criterion validity was the performance of
      stroke patients vs. healthy controls - which was lower both on the
      neuropsychological tests and on the SLB for patients. The pattern of correlations
      between neuropsychological tests and the SLB sub-tests for the respective
      dimensions showed overall moderate correlations in the predicted directions. We
      conclude that the SLB applications were able to discriminate the dimensions that
      they were designed to assess. 

PMID- 24875701
TI  - What do we mean by social networking sites?
AB  - The purpose of this study was to explore people's conceptual understanding of
      Social Networking Sites (SNSs) through exploring the combined use of a range of
      popular SNSs, including Facebook, Twitter, Myspace, Instagram, Tumblr, LinkedIn
      and Google Plus. Seventy-three adults, aged 18 to 63, participated in an online
      survey that used open-ended questions to ask how participants define and use
      different SNSs. Four themes were identified, including the explicit presentation
      and interpretation of different selves, the love-hate relationship with SNSs,
      privacy and danger concerns, and limited SNS knowledge. The findings from this
      study suggest that researchers need to consider how people use SNSs in
      combination as this influences the decisions people make about which SNS accounts
      they use and how they present themselves on these sites. 

PMID- 24875702
TI  - Online perspective-taking as an intervention tool against cyberbullying.
AB  - This study will examine the use of an online role-playing experiment as a
      cyberbullying intervention tool. The study will be carried out among 14 - to 18
      year old adolescents (N = 200). Respondents will be assigned a fictitious
      character and a role (perpetrator, victim or bystander) in a cyberbullying
      situation. They will be asked to identify with this character and act accordingly
      in an initiated mock, but realistic online bullying situation. We expect, based
      on role playing literature and bullying prevention programs, a positive change in
      the adolescents' behavioral intentions (e.g. defending a victim). 

PMID- 24875703
TI  - Grief support groups in second life.
AB  - Online grief support groups serve as an avenue of support for the bereaved. In
      the past, facilitators have criticized the ability to provide group participants
      with a sense of therapeutic support, given the lack of face-to-face interaction
      in online groups. However, with the growing technological advances, 3-D virtual
      worlds, such as Second Life, may increase a participant's sense of presence and
      improve their group experience. A web-based survey was utilized to explore
      facilitator attitudes towards grief support groups in Second Life. 

PMID- 24875704
TI  - How do client and therapists in online text therapy experience their exchanges
      and relationship?
AB  - The impact of online therapy text exchanges and the client-therapist alliance was
      compared to previously published means and standard deviations on face-to-face
      therapy using an aggregate benchmarking strategy. Further, the moderating effects
      of 4 participant factors found significant in the face-to-face therapy literature
      was investigated using mixed modeling analytic techniques. Thirty therapists and
      30 clients visited an online site to report weekly to complete session impact and
      therapeutic alliance measures for a minimum of six weeks, which allowed for a
      naturalistic and nuanced examination of the process of online text psychotherapy.
      The impact of exchanges and client-therapist alliance in text therapy were
      similar to but in some respects more positive than previous evaluations of face
      to-face therapy. A notable exception was substantially lower Arousal scores
      replicating the previously-observed online calming effect. The significance of
      participant factors previously found to influence impact and alliance in face-to
      face therapy was not replicated except that therapists with the more symptomatic
      clients rated their text exchanges as less smooth and comfortable. 

PMID- 24875705
TI  - Exploring Identity Motives in Twitter Usage in Saudi Arabia and the UK.
AB  - This study explores identity motives for using a microblogging site (Twitter)
      among Internet users in Saudi Arabia and the UK. The former boasts the world's
      highest per capita use of Twitter, which provides a forum in which users have
      more opportunity for self-expression than they do in the offline world, and is
      not subject to the heavy censorship which the Saudi government imposes on other
      Internet content [1]. Approximately 5000 tweets from the period April-May 2013
      were coded and analyzed, using Motivated Identity Construction Theory as a
      conceptual framework [2]. This theory proposes six universal identity motives of
      meaning, belonging, continuity, distinctiveness, efficacy, and self-esteem. We
      consider these motives in turn, and examine their relative prominence in an
      online context. Support was found for all six universal motives, but the relative
      prominence of motives and the ways in which they were pursued appeared to depend
      on the affordances of both the OSN in question, Twitter and the cultural context
      in which the user was posting: Saudi users appeared to seek distinctiveness,
      whereas for British users, belonging was a more salient motive. Themes related to
      meaning, efficacy, and self-esteem were detected frequently, whereas themes
      related to continuity were less apparent. 

PMID- 24875707
TI  - Section v. Clinical observations.

PMID- 24875706
TI  - The impact of cyberstalking: the lived experience - a thematic analysis.
AB  - Cyberstalking (CS) can have major psychosocial impacts on individuals. Victims
      report a number of serious consequences of victimization such as increased
      suicidal ideation, fear, anger, depression, and post traumatic stress disorder
      (PTSD) symptomology. Research is largely limited to quantitative outcome
      research. This study examines the diversity of experiences reported by people who
      define themselves as having been cyberstalked. Thematic analysis was used to
      explore 100 CS victim narratives, gathered by means of an online survey
      questionnaire designed to capture structured text responses. Five emergent themes
      were evident in the data: control and intimidation; determined offender;
      development of harassment; negative consequences; and lack of support. Findings
      identify similarities and differences to traditional stalking, along with the
      necessity of support for victims and illustration of the negative impacts this
      form of harassment produces. 

PMID- 24875708
TI  - Virtual reality graded exposure therapy with arousal control for the treatment of
      combat related posttraumatic stress disorder: a follow up case series.
AB  - Important challenges confronting DOD/military medical care are that of
      maintaining or increasing quality of care and increasing the effectiveness of
      treatments for warriors diagnosed with Posttraumatic Stress Disorder (PTSD)
      secondary to their combat deployments to Iraq and/or Afghanistan. Virtual Reality
      Graded Exposure Therapy with Arousal Control (VR-GET) has demonstrated a positive
      treatment effectiveness resulting in significant reductions of PTSD symptom
      severity. This positive treatment effectiveness has been maintained for up to 22
      weeks after VR-GET therapy was completed. A robust methodology for the assessment
      of Virtual Reality efficacy suggests that the ideal time for follow-up begins at
      twelve months. Others have suggested that follow-up should occur between two and
      four years post treatment. In this report we describe the outcome of VR-GET for
      the treatment of combat-related PTSD with three warriors between five and seven
      years following their having completed treatment. 

PMID- 24875710
TI  - Section VI. Work in Progress.

PMID- 24875709
TI  - Validation of VR-based Software for Binge Eating Treatment: Preliminary Data.
AB  - This study shows preliminary data on the validity of a new virtual reality-based
      application for cue-exposure treatment of binge eating in bulimia nervosa and
      binge eating disorder. Thirty-eight undergraduate students without eating
      disorders were exposed to several virtual environments with different foods in
      four different contexts (kitchen, dining-room, bedroom, and bakery/cafe).
      Participants were asked to indicate the level of food craving experienced in each
      situation. They also completed the Spanish version of the State and Trait Food
      Cravings Questionnaires. The results suggest that virtual reality is an effective
      technology for eliciting food craving, especially in the case of participants
      with high reactivity to food cues, and those who were hungry or experienced
      strong desire to eat during the experiment. 

PMID- 24875711
TI  - Assessing the mental frame syncing in the elderly: a virtual reality protocol.
AB  - Decline in spatial memory in the elderly is often underestimated, and it is
      crucial to fully investigate the cognitive underpinnings of early spatial
      impairment. A virtual reality-based procedure was developed to assess deficit in
      the "mental frame syncing", namely the cognitive ability that allows an effective
      orientation by synchronizing the allocentric view-point independent
      representation with the allocentric view-point dependent representation. A pilot
      study was carried out to evaluate abilities in the mental frame syncing in a
      sample of 16 elderly participants. Preliminary results indicated that the general
      cognitive functioning was associated with the ability in the synchronization
      between these two allocentric references frames. 

PMID- 24875712
TI  - Intersubjectivity in video interview.
AB  - The concept of relationship has rapidly evolved over the past few years, since
      the emergence of the internet network and the development of remote communication
      and exchanges. The emergence of cyberculture with the development of the internet
      has led to a new representation of the social link, in which communication never
      stops. In this context, computer mediated intersubjective relationships represent
      a main line of thinking and research. Thus, can we consider for example that
      relationship is only composed of an informational exchange? Would there be other
      dimensions possibly missing in computer mediated relationships? In this case, how
      could we re-introduce these aspects, "re-humanize" the remote relationships? New
      practices in psychology emerge with the ICT usage, both in the fields of research
      and for therapeutic purposes. Some fields like medicine already use remote health
      platforms that have proven useful in certain situations. In the field of remote
      clinical psychology, different media are used that contribute to the framework
      definition of the remote clinical interview, where the concept of relation holds
      a central place. Videoconference enables the introduction of an important element
      from the point of view of sensoriality: the body image, which engages the
      subjects' interaction in a different way than in a written or verbal exchange.
      But is the use of videoconference sufficient to establish a clinical framework
      comparable to the traditional one? How can the computer-mediated relationship
      enable and establish a potential object relation, rather than a mirrored one?
      Thinking through an online adaptation of the clinical interview framework led to
      the elaboration of a specific tool dedicated to this purpose and to research into
      the access to intersubjectivity in clinical video interview. This study's
      encouraging results have fostered the pursuit of this experience in the form of a
      platform dedicated to the conduction of clinical interviews through
      videoconferencing for psychotherapists and patients at large. A methodological
      analysis accompanies this research work, in order to continuously observe this
      specific clinical practice, which can be used in different fields of psychology
      and different psychotherapeutic methods. 

PMID- 24875713
TI  - NIRS Study of the Effects of Computerized Brain Training Games for Cognitive
      Rehabilitation of Major Depressive Disorder Patients in Remission: A Pilot Study.
AB  - We used functional Near-Infrared Spectroscopy (fNIRS) to estimate brain activity
      in Major Depressive Disorder (MDD) patients (in remission), while they played a
      computerized brain training games for cognitive rehabilitation. MDD is
      characterized by marked deterioration in affect as well as significant impairment
      in cognitive function. It was found, that depressed patients showed long-lasting
      impaired cognitive performance on cognitive demanding tasks despite significant
      improvement in the depression symptoms. Previous studies have shown that video
      games can improve cognitive functions. But assessment was made only with
      cognitive tests. The main objective of this research was to study the effects of
      brain training games on cognitive functions of MDD patients in remission with
      objective instrumental NIRS method. Tissue oxygen saturation (StO2) and absolute
      concentrations of oxyhemoglobin ([O2Hb]), deoxyhemoglobin ([HHb]) and total
      hemoglobin ([tHb]) were measured by functional near-infrared spectroscopy (fNIRS)
      - Oxyprem (BORL, Zurich, Switzerland). Preliminary results are discussed. 

PMID- 24875714
TI  - Usability Assessment of the Virtual Multitasking Test (V-MT) for Elderly People.
AB  - In the last decades an increasing number of psychological researches have used
      Virtual Reality (VR) technology in different fields. Nevertheless, few studies
      used Virtual Environments (VEs) with a sample of older users. The aim of the
      present study is to assess the usability of the Virtual Multitasking Test (V-MT),
      which consists in a virtual apartment created to assess cognitive functions in
      elderly people. This study reports the preliminary results to support the
      development of a VE in which elderly people feel present and fully immersed. 

PMID- 24875715
TI  - Addressing Cultural Contexts in the Management of Stress via Narrative and Mobile
      Technology.
AB  - In developing applications for stress management and mental health, developers
      have largely ignored cultural context in design, opting instead to produce apps
      for a general audience. However, apps designed without a specific population in
      mind actually have limited reach. Generally stress trackers and socalled
      "therapists in your pocket", tend to be lost among a jungle of other generic apps
      that appeal only to the quantified self population and those already predisposed
      to help-seeking behavior. To reach a broader audience, designing for a specific
      population may have appeal. The AppHappy Project's Journey to the West is a
      mobile app being developed by a multidisciplinary group of students at the
      University of Pennsylvania. The objective is to promote better stress management
      and mental health among Asian international college students and facilitate their
      social integration with the general student population. With a prevalence of
      depression twice that of domestic college students, a reluctance to engage in
      help-seeking behavior due to stigma, and the challenge of cultural integration,
      creating interventions for this population requires a different approach to app
      mediated therapy. Journey to the West packages bite-sized pieces of Cognitive
      Behavioral Therapy techniques within the framework of a role-playing game. Every
      element of its design-from its characters to its art style, from its narrative to
      its mechanics to its approach to community features-is rooted in a culturally
      appropriate context. An avatar serves as a surrogate of self while experiencing
      externalized stressors. Each quest blends therapeutic elements into gameplay with
      the goal of building resilience towards stressful events. 

PMID- 24875719
TI  - Cellular automata simulation of osteoblast growth on microfibrous-carbon-based
      scaffolds.
AB  - The objective of this study was to investigate the use of three fibrous carbon
      materials (T300, P25, and P120) for bone repair and develop and validate
      theoretical and computational methods in which bone tissue regeneration and
      repair could be accurately predicted. T300 was prepared from polyacrylonitrile
      precursor while P25 and P120 fibers were prepared from pitch, both common fiber
      precursors. Results showed that osteoblast growth on carbon scaffolds was
      enhanced with increased crystallinity, surface roughness, and material
      orientation. For unidirectional scaffolds at 120 h, there was 33% difference in
      cell growth between T300 and P25 fibers and 64% difference between P25 and P120
      fibers. Moreover, for multidirectional fibers at 120 h, there was 35% difference
      in cell growth between T300 and P25 fibers and 43% difference between P25 and
      P120 fibers. Results showed that material alignment was integral to promoting
      cell growth with multidirectional scaffolds having the capacity for greater
      growth over unidirectional scaffolds. At 120 h there was 24% increase in cell
      growth between unidirectional alignment and multidirectional alignment on high
      crystalline carbon fibers. Ultimately, data indicated that carbon scaffolds
      exhibited excellent bioactivity and may be tuned to stimulate unique reactions.
      Additionally, numerical and computational simulations provided evidence that
      corroborated experimental data with simulations. Results illustrated the
      capability of cellular automata models for assessing osteoblast cell response to
      biomaterials. 

PMID- 24875720
TI  - Prenatal and postnatal development of synapses and acetylcholinesterase staining
      in the dentate gyrus of the rhesus monkey.
AB  - Morphogenesis, distribution of cholinergic enzyme acetylcholinesterase and
      synaptogenesis in the dentate gyrus of the rhesus monkey during the pre- and
      postnatal periods of development were examined using histological, histochemical
      and ultrastructural methods. The pattern of neuronal differentiation in the
      dentate gyrus demonstrated distinct superficial-to-deep and lateral-to-medial
      gradients. The histochemical reaction for acetylcholinesterase was present on
      gestation day 120 as minimal staining in the supragranular band and in the inner
      one-third of the dentate molecular layer. At term, the laminar distribution of
      the enzyme assumed mature pattern although considerable enhancement in staining
      intensity was achieved postnatally. At term and at 9 months of postnatal age, the
      most pronounced enzyme activity was found in the supragranular band and in the
      inner one-third of the molecular layer. Synaptogenesis in the dentate molecular
      layer was characterized by the early formation of axo-dendritic contacts on
      dendritic trunks and branches followed by the appearance of synapses on simple
      and complex spines. Spines were detected infrequently on gestation day 132. On
      day 148, they ranged in morphology from short stubby protrusions to pedunculated,
      triangular processes. The majority of the spines exhibited flat postsynaptic
      surfaces. Complex, synapse-bearing U- and W-shaped spines were observed rarely at
      this age but appeared more frequently at term and at 15 months of postnatal age.
      However, at all ages, including 15 months postnatally, synapses on flat-surfaced
      simple spines predominated. Most synapses were of the asymmetric variety. With
      certain exceptions, these features of development of the rhesus dentate gyrus
      resemble the reported patterns of postnatal ontogenesis of this structure in the
      rat. However, the ingrowth of cholinergic afferents and the major modifications
      in synapse structure occur prenatally in the rhesus monkey during the second half
      of the gestation period. This temporal difference between the two species should
      receive consideration in the planning of neuroplasticity experiments designed to
      explore lesion-induced adaptations in afferent growth and synaptogenesis in the
      rhesus dentate gyrus. 

PMID- 24875721
TI  - Response of neuropeptides and neurotransmitter binding sites in the retina and
      brain of the developing chick to reduced visual input.
AB  - The effect of 17 days of monocular suture of eyelids of day-old chicks upon
      levels of neuropeptides and high affinity binding sites was studied. A
      significant reduction of met-enkephalin, but not of substance P or neurotensin,
      was observed in the retina of the eye receiving dim and unpatterned light.
      Retinal muscarinic, dopaminergic, opiate, and benzodiazepine receptors appeared
      unaltered by the experimental procedure. Levels of neuropeptides were not
      significantly changed in optic lobes contralateral to and innervated by the
      sutured eyes relative to the optic lobes receiving afferentation from the open
      eyes. Seventeen days after unilateral enucleation of new-hatched chicks, the
      neuropeptide content of the smaller denervated optic lobes did not differ from
      that of the lobes receiving an intact neuronal input. 

PMID- 24875722
TI  - Neonatal hypothyroidism and early undernutrition affect myelin and myelin
      precursor membranes in a different way.
AB  - The lipid and protein composition as well as the activity of 2'3' cyclic
      nucleotide 3' phosphohydrolase (CNPH) and the distribution of individual proteins
      separated by SDS-PAGE were studied in myelin and in a fraction closely related to
      myelin or assumed to be a precursor membrane of mature myelin (fraction SN4)
      isolated from 20-day-old rats made hypothyroid at birth or submitted to early
      malnutrition. In both experimental conditions lipid and protein components were
      found to be reduced in myelin when data were expressed as mg/g fresh tissue, but
      the results were close to those obtained in normal controls when data were
      expressed as mg/mg total protein of each fraction. CNPH activity was normal in
      myelin but markedly reduced in fraction SN4. Although the results appear to
      suggest that both experimental conditions produce a reduction in the amount of
      myelin but no qualitative changes, the data obtained with SDS-PAGE show that the
      distribution of the various types of proteins present in this fraction and
      fraction SN4 was abnormal. Myelin and fraction SN4 isolated from malnourished
      animals displayed a protein profile which was quite similar to that found in
      fraction SN4 isolated from normal rats, indicating a delay in the process of
      myelin maturation. The changes in protein composition of myelin and fraction SN4
      produced by neonatal hypothyroidism on the other hand differed clearly from those
      produced by early malnutrition; the ratio small basic protein: large basic
      protein (SBP:LBP) was found to be reduced in both membrane fractions in the
      former condition and the protein patterns of myelin and that of fraction SN4 were
      different, at variance with what was found in the case of malnourished animals.
      Our findings appear to suggest that the effects of early malnutrition and
      neonatal hypothyroidism upon myelin and myelin-related membranes are different,
      and that myelination is more affected in the latter condition. 

PMID- 24875723
TI  - Critical periods for the role of ornithine decarboxylase and the polyamines in
      growth and development of the rat: Effects of exposure to alpha
      difluoromethylornithine during discrete prenatal or postnatal intervals.
AB  - The roles of ornithine decarboxylase (ODC) and the polyamines in fetal and
      neonatal development were examined through the use of alpha
      difluoromethylornithine (DFMO), a specific irreversible inhibitor of ODC.
      Administration to pregnant rats of 500 mg/kg of DFMO every 12 h for a 4-day
      period (8 DFMO injections) resulted in fetal and neonatal death; DFMO early in
      gestation produced fetal resorption whereas late gestational exposure did not
      compromise fetal viability but instead resulted in a delayed toxic effect, with
      high mortality in the first postnatal week. Generalized toxicity of DFMO was not
      apparent in later developmental periods, as 4 days of DFMO treatment begun
      postnatally did not produce any neonatal death. Shortening the course of
      gestational DFMO treatment to 2.5 days (5 DFMO injections) also did not adversely
      affect fetal or neonatal viability and thus permitted identification of critical
      periods in which various tissues are sensitive to DFMO. Examination of growth
      patterns of brain, heart and kidney and of neurochemical development of central
      and peripheral catecholaminergic neurons indicated that different critical
      periods exist for effects of DFMO on each tissue or even on the various cell
      types within a tissue. The separable sensitivities were apparent even though the
      effects of DFMO on ODC and the polyamines for any given treatment period were
      fairly uniform in all tissues studied. These results indicate that the
      ODC/polyamine system plays multiple roles in fetal survival and in tissue growth
      during discrete periods of development; because the time course of cellular
      maturation differs for each tissue or cell population, DFMO administered during
      any one brief period can produce organ-specific developmental deficits. 

PMID- 24875724
TI  - Fine structure of the human fetal cervical ganglia.
AB  - Cervical sympathetic ganglia from nine human fetuses in the second trimester were
      studied by light-, fluorescence- and electronmicroscopy. Within ganglia granule
      containing cells, corresponding to the small intensely fluorescent (SIF) cells,
      were sparsely distributed along capillaries. Satellite cells were interspersed
      among neuronal cell types. All stages of the developing sympathetic ganglion
      cells were present. Primitive sympathetic ganglion cells (PSC) had dark nuclei
      and scanty cytoplasm in which the rough endoplasmic reticulum (RER) was not
      organized. These cells often contacted each other vs the more mature pattern of
      satellite cell support. Neuroblasts had more voluminous cytoplasm, RER was more
      apparent than in the PSCs and dense-cored vesicles and mitochondria were more
      frequently seen. Their diameter was between 5 and 20 MUm. The most mature
      neuronal cell type, the young sympathetic ganglion cell, was often covered by
      satellite cells, but synaptic contacts often appeared on the somata. Maturity of
      the cells was underscored by an abundant RER and ribosomes organized as Nissl
      bodies. Indeed all the organelles typical of an adult ganglion cell were present
      and fully developed, although in smaller amounts. However, the diameter (20-30
      MUm) of the cells was smaller than in adult ganglia. All ganglia examined
      possessed mature axodendritic and axosomatic synapses. Large dense-cored vesicles
      were found in some neuroblasts and in young sympathetic ganglion cells. However,
      neither cytoplasmic nor synaptic small dense-cored vesicles were seen. These
      morphological results correlate with pharmacological and immunohistochemical data
      on human fetal tissue which show that both cholinergic and adrenergic receptors,
      catecholamine-synthesizing enzymes and enkephalin are developed by the end of the
      first trimester. 

PMID- 24875726
TI  - Axonal transport of gangliosides in the visual system of the developing chick
      embryo.
AB  - Chick embryos aged 7-18 days of development were injected with N-[ (3)H]
      acetylmannosamine into one eye. The labeling of gangliosides was significantly
      higher in the contralateral- than in the ipsilateral-optic tectum in embryos aged
      14 days or older. Comparison of the radioactivities of thin-layer chromatograms
      of gangliosides from the contralateral- and ipsilateral-optic tecta showed that
      in the 14-day-old embryo about 56 and 29% of the transported radioactivity
      chromatographed as GD1a and GT1, respectively. Most of the remaining
      radioactivity chromatographed in the zone of less complex gangliosides (GM2-GD3,
      3%; GM3, 6%). In the 18-day-old embryo about 72% of the transported radioactivity
      chromatographed as GD1a; the radioactivity in the zone of GT1 was reduced to
      about 2% and that in the less complex gangliosides remained low (about 14% in the
      zone of GM2-GD3 and 7% in the zone of GM3). 

PMID- 24875725
TI  - The arachnoid granulations of the newborn human: An ultrastructural study.
AB  - Portions of the superior sagittal sinus and lacunae laterales containing
      arachnoid villi and granulations from 8 full-term newborn babies were studied by
      transmission electron microscopy. Arachnoid proliferations from 3 subjects were
      distended and fixed in vitro by applying a differential pressure of 8 cm H2O to
      the subarachnoid aspect of the tissues. The remaining cases were fixed in a
      collapsed state. Distended arachnoid proliferations showed morphologic
      characteristics associated with similar functional structures in experimental
      animals: shortened and enlarged interendothelial spaces; micropinocytotic
      activity and a system of endothelial-lined tubules. All this is taken as evidence
      that arachnoid proliferations in newborn babies could already be engaged in
      cerebrospinal fluid absorption. 

PMID- 24875727
TI  - Effects of changes in neonatal thyroid status on the development of neuropeptide
      systems in the rat brain.
AB  - The effects of neonatal thyroid deficiency or hyperthyroidism on the development
      of neurones containing certain neuropeptides was examined in the brains of rats
      killed at two weeks of age. Five brain areas were dissected and extracted for
      radioimmunoassay measurement of vasoactive intestinal polypeptide (VIP),
      somatostatin, cholecystokinin octapeptide (CCK), substance P and neurotensin,
      whilst corresponding immunocytochemical data were obtained from a quantitative
      morphological analysis of cell bodies in the cingulate cortex. The two methods of
      analysis did not always agree, but in hypothyroidism both the concentration of
      VIP and the number of cells containing VIP-like immunoreactivity were
      significantly decreased in the anterior and posterior cingulate cortex. In
      contrast to these effects on the late maturing VIP neurones, the earlier
      developing somatostatin system was relatively unaffected, whilst neuropeptides
      localized in cortical fibres rather than cell bodies (such as substance P and
      neurotensin) were found by radioimmunoassay to be elevated. Hyperthyroidism had
      less marked effects than neonatal thyroidectomy, although the concentration of
      CCK (but not the number of immunostained cells) was significantly increased in
      the cingulate cortex. Radioimmunoassay results from three subcortical areas
      showed a decrease in VIP concentration in the hypothyroid hypothalamus, and in
      hyperthyroidism significant elevations of VIP in the basal ganglia, somatostatin
      in the hypothalamus and CCK in the hippocampus. It appears that in the brain
      areas studied thyroid disorders result in dis-synchronous shifts in the
      developmental patterns of the different neuropeptides, and that the effects of
      thyroid hormone on peptides as on other transmitters are critically dependent on
      the developmental profile of the system in question. 

PMID- 24875728
TI  - Is there a relationship between executive functions and academic success in
      children with neurofibromatosis type 1?
AB  - The present study aimed to compare the executive function (EF) of children with
      neurofibromatosis type 1 (NF1) to those of typically developing children and to
      investigate whether those abilities could predict the child's academic success in
      terms of academic skills and enablers. Twenty-nine children with NF1 and 27 age
      and-gender-matched controls (aged 8-16 years) were examined with two tests to
      measure EF in an ecologically valid manner: the Behavioural Assessment of the
      Dysexecutive Syndrome in Children (BADS-C) and the parent questionnaire for the
      Behavior Rating Inventory of Executive Function (BRIEF). In order to evaluate
      academic success we used the Academic Competence Evaluation Scales (ACES). The
      performance of the NF1 group was significantly lower on the Water and Key search
      subtest of the BADS-C and on four scales of the BRIEF: initiate; working memory;
      plan/organise and organisation of materials. Significant correlations and
      predictive models via regression analysis were generated for: BADS-C, BRIEF and
      ACES scores. Based on these findings, children with NF1 have executive
      dysfunction that partially accounts for their difficulties in academic
      achievements. 

PMID- 24875729
TI  - Induction of PD-L1 on monocytes: a new mechanism by which IVIg inhibits mixed
      lymphocyte reactions.
AB  - Allograft rejection and graft-versus-host disease (GvHD) are frequent
      complications following solid organ or stem cell transplantation in which T cell
      activation plays a central role. Despite the development of new immunosuppressive
      drugs that improve the success rate of transplantation, allograft survival
      continues to be a challenge. Recently, intravenous immunoglobulin (IVIg) has been
      proposed as prophylaxis and post-transplant treatment to reduce acute rejection
      episodes. IVIg is a therapeutic agent that is known to down-modulate T cell
      functions in patients with autoimmune disorders. To test the hypothesis that this
      immunomodulatory effect could be beneficial in the context of transplantation, we
      used mixed lymphocyte reactions (MLR) as an in vitro model of allograft rejection
      and GvHD. Our results show that IVIg strongly inhibits the MLR as evaluated by IL
      2 secretion, a well-known marker of T cell activation. IVIg also modulates the
      secretion of other pro-(IL-6, IFN-gamma) and anti-inflammatory (IL-1RA)
      cytokines. More importantly, we show that IVIg induces monocytes with a CD80(low)
      PD-L1(high) phenotype and that blockade of PD-L1 partially abrogates the
      inhibitory effect of IVIg. We have thus identified a new mechanism by which IVIg
      inhibits T cell functions in the context of transplantation, supporting the
      potential usefulness of IVIg in the prevention or treatment of graft rejection
      and GvHD.

PMID- 24875730
TI  - microRNAs: novel players in hepatitis C virus infection.
AB  - Hepatitis C virus (HCV) is a single-stranded, positive-sense RNA virus. About 70%
      of patients exposed to HCV develop a chronic infection, which can lead to
      scarring of the liver and ultimately to cirrhosis, liver failure, and
      hepatocellular carcinoma. For the past decade, the standard therapy for HCV
      infection has been a combination of interferon-alpha and ribavirin. In recent
      years, direct-acting antiviral agents, boceprevir and telaprevir, have been added
      to the therapeutic regimen and considerably improve the cure rates for HCV
      infection. However, the treatment continues to cause substantial side effects and
      is associated with drug resistance due to frequent mutations in the HCV RNA
      genome resulting from the low fidelity of its RNA polymerase. MicroRNAs (miRNAs)
      are a class of small, non-coding RNAs approximately 22 nucleotides in length.
      They are derived from cellular or viral transcripts and bind to their target
      mRNAs in a sequence-specific manner, resulting in either mRNA cleavage or
      translational repression and subsequent modulation of the expression of the
      majority of the protein-coding genes. miRNAs have been implicated in regulating
      multiple aspects of HCV life cycles and certain miRNAs serve as essential
      mediators for the interferon-based antiviral therapy. Furthermore, recent studies
      have documented the potential values of miRNAs as novel therapeutic targets
      against hepatitis C infectivity.

PMID- 24875731
TI  - Effect of a teleretinal screening program on eye care use and resources.
AB  - IMPORTANCE: Telemedicine is a useful clinical method to extend health care to
      patients with limited access. Minimal information exists on the subsequent effect
      of telemedicine activities on eye care resources. OBJECTIVE: To evaluate the
      effect of a community-based diabetic teleretinal screening program on eye care
      use and resources. DESIGN, SETTING, AND PARTICIPANTS: The current study was a
      retrospective medical record review of patients who underwent diabetic
      teleretinal screening in the community-based clinics of the Atlanta Veterans
      Affairs Medical Center from October 1, 2008, through March 31, 2009, and who were
      referred for an ophthalmic examination in the eye clinic. EXPOSURES: Clinical
      medical records were reviewed for a 2-year period after patients were referred
      from teleretinal screening. The following information was collected for analysis:
      patient demographics, referral and confirmatory diagnoses, ophthalmology clinic
      visits, diagnostic procedures, surgical procedures, medications, and spectacle
      prescriptions. MAIN OUTCOMES AND MEASURES: The accuracy between referring and
      final diagnoses and the eye care resources that were used in the care of referred
      patients. RESULTS: The most common referral diagnoses were nonmacular diabetic
      retinopathy (43.2%), nerve-related disease (30.8%), lens or media opacity
      (19.1%), age-related macular degeneration (12.9%), and diabetic macular edema
      (5.6%). The percentage of agreement among these 5 visually significant diagnoses
      was 90.4%, with a total sensitivity of 73.6%. Diabetic macular edema required the
      greatest number of ophthalmology clinic visits, diagnostic tests, and surgical
      procedures. Using Medicare cost data estimates, the mean cost incurred during a 2
      year period per patient seen in the eye clinic was approximately $1000.
      CONCLUSIONS AND RELEVANCE: Although a teleretinal screening program can be
      accurate and sensitive for multiple visually significant diagnoses, measurable
      resource burdens should be anticipated to adequately prepare for the associated
      increase in clinical care.

PMID- 24875733
TI  - Factors influencing K-wire migration in tension-band wiring of olecranon
      fractures.
AB  - BACKGROUND: Tension-band wiring is a popular method of internal fixation for
      simple olecranon fractures. Although fracture union rates and clinical outcomes
      are good, up to 80% of patients require removal because of prominent/symptomatic
      metalwork. The current literature remains unclear as to the best orientation of
      the longitudinal wires to minimize hardware failure. The aim of this study was to
      determine the surgically modifiable factors related to spontaneous wire pullout.
      METHODS: A retrospective review of hospital theater records over a period of 6
      years was performed to identify all olecranon tension-band wire procedures.
      Preoperative radiographs were used to confirm and classify the fracture.
      Intraoperative and postoperative radiographs were analyzed for a number of wire
      associated variables: wire length within the ulna, medullary/cortical position,
      parallelism of wires, proximal wire prominence, wire angle relative to the ulna,
      distance from the articular surface, fracture gap, and subsequent pullout.
      RESULTS: A total of 182 wires were analyzed. The mean age was 52.5 years, and the
      mean radiographic follow-up period was 7.3 months. Intramedullary wires had a
      mean pullout of 5.5 mm compared with 2.4 mm for transcortical wires (P < .0001).
      A multiple regression model noted 7 independent variables affecting wire pullout:
      age, bent wires, medullary/transcortical wire positioning, proximal prominence,
      ulnar shaft angle, distance from the articular surface, and articular step.
      CONCLUSION: To minimize postoperative pullout of wires, we suggest anatomic
      reduction and transcortical wire orientation, without bending, in the subchondral
      bone close to the articular surface.

PMID- 24875732
TI  - Upregulation of transforming growth factor-beta signaling in a rat model of
      rotator cuff tears.
AB  - BACKGROUND: Muscle atrophy, fatty infiltration, and fibrosis of the muscle have
      been described as important factors governing outcome after rotator cuff injury
      and repair. Muscle fibrosis is also thought to have a role in determining muscle
      compliance at the time of surgery. The transforming growth factor-beta (TGF-beta)
      pathways are highly conserved pathways that exert a potent level of control over
      muscle gene expression and are critical regulators of fibrosis in multiple organ
      systems. It has been shown that TGF-beta can regulate important pathways of
      muscle atrophy, including the Akt/mammalian target of rapamycin pathway. The
      purpose of this study was to evaluate the expression of TGF-beta and its
      downstream effectors of fibrosis after a massive rotator cuff tear (RCT) in a
      previously established rat model. METHODS: To simulate a massive RCT,
      infraspinatus and supraspinatus tenotomy and suprascapular nerve transection were
      performed on Sprague-Dawley rats with use of a validated model. Two and 6 weeks
      after surgery, supraspinatus muscles were harvested to study alterations in TGF
      beta signaling by Western blotting, quantitative polymerase chain reaction, and
      histologic analysis. RESULTS: There was a significant increase in fibrosis in the
      rotator cuff muscle after RCT in our animal model. There was a concomitant
      increase in TGF-beta gene and protein expression at both 2 and 6 weeks after RCT.
      Evaluation of the TGF-beta signaling pathway revealed an increase in SMAD2
      activation but not in SMAD3. There was an increase in profibrotic markers
      collagen I, collagen III, and alpha-smooth muscle actin. CONCLUSIONS: TGF-beta
      signaling is significantly upregulated in rat supraspinatus muscles after RCTs.

PMID- 24875734
TI  - Sticking to it: tracking the paths of integrin signalling.

PMID- 24875737
TI  - Embryonic stem cell identity grounded in the embryo.
AB  - Pluripotent embryonic stem cells (ESCs) can be derived from blastocyst-stage
      mouse embryos. However, the exact in vivo counterpart of ESCs has remained
      elusive. A combination of expression profiling and stem cell derivation
      identifies epiblast cells from late-stage blastocysts as the source, and
      functional equivalent, of ESCs. 

PMID- 24875735
TI  - Oncogenic roles of EMT-inducing transcription factors.
AB  - The plasticity of cancer cells underlies their capacity to adapt to the selective
      pressures they encounter during tumour development. Aberrant reactivation of
      epithelial-mesenchymal transition (EMT), an essential embryonic process, can
      promote cancer cell plasticity and fuel both tumour initiation and metastatic
      spread. Here we discuss the roles of EMT-inducing transcription factors in
      creating a pro-tumorigenic setting characterized by an intrinsic ability to
      withstand oncogenic insults through the mitigation of p53-dependent
      oncosuppressive functions and the gain of stemness-related properties. 

PMID- 24875739
TI  - Galectins CLIC cargo inside.
AB  - Clathrin-independent endocytosis removes membrane receptors and other proteins
      from the cell surface, yet the mechanisms controlling this process remain
      unclear. Galectin-3 is now shown to regulate the biogenesis of a subpopulation of
      clathrin-independent carriers (CLICs). Galectin-3 binds to glycosylated cargo
      proteins and interacts with membrane glycosphingolipids to induce membrane
      deformation and CLIC formation. 

PMID- 24875738
TI  - A centrosomal route for cancer genome instability.
AB  - Despite the widespread occurrence of aneuploidy in cancer cells, the molecular
      causes for chromosomal instability are not well established. Cyclin B2 is now
      shown to control a pathway - involving the centrosomal kinases aurora A and Plk1
      and the tumour suppressor p53 - the alteration of which causes defective
      centrosome separation, aneuploidy and tumour development. 

PMID- 24875740
TI  - Cadherin adhesion controlled by cortical actin dynamics.
AB  - Cadherin-containing cell-cell junctions respond to intercellular tension by
      increasing their size, strength and complexity. The mechanical regulation of
      cadherin adhesions is now shown to involve myosin-dependent tension in the
      cortical actomyosin cytoskeleton. This reduces actin turnover to decrease the
      mobility of cadherin molecules and increase their concentration at junctions. 

PMID- 24875736
TI  - Cargo recognition and trafficking in selective autophagy.
AB  - Selective autophagy is a quality control pathway through which cellular
      components are sequestered into double-membrane vesicles and delivered to
      specific intracellular compartments. This process requires autophagy receptors
      that link cargo to growing autophagosomal membranes. Selective autophagy is also
      implicated in various membrane trafficking events. Here we discuss the current
      view on how cargo selection and transport are achieved during selective
      autophagy, and point out molecular mechanisms that are congruent between
      autophagy and vesicle trafficking pathways. 

PMID- 24875746
TI  - Microwave-assisted preparation of nucleoside-phosphoramidites.
AB  - Microwave-assisted phosphitylation of sterically hindered nucleosides is
      demonstrated to be an efficient method for the preparation of corresponding
      phosphoramidites (otherwise onerous under standard conditions) and is shown to be
      general in its applicability. 

PMID- 24875747
TI  - Establishing a regional nitrogen management approach to mitigate greenhouse gas
      emission intensity from intensive smallholder maize production.
AB  - The overuse of Nitrogen (N) fertilizers on smallholder farms in rapidly
      developing countries has increased greenhouse gas (GHG) emissions and accelerated
      global N consumption over the past 20 years. In this study, a regional N
      management approach was developed based on the cost of the agricultural response
      to N application rates from 1,726 on-farm experiments to optimize N management
      across 12 agroecological subregions in the intensive Chinese smallholder maize
      belt. The grain yield and GHG emission intensity of this regional N management
      approach was investigated and compared to field-specific N management and
      farmers' practices. The regional N rate ranged from 150 to 219 kg N ha(-1) for
      the 12 agroecological subregions. Grain yields and GHG emission intensities were
      consistent with this regional N management approach compared to field-specific N
      management, which indicated that this regional N rate was close to the
      economically optimal N application. This regional N management approach, if
      widely adopted in China, could reduce N fertilizer use by more than 1.4 MT per
      year, increase maize production by 31.9 MT annually, and reduce annual GHG
      emissions by 18.6 MT. This regional N management approach can minimize net N
      losses and reduce GHG emission intensity from over- and underapplications, and
      therefore can also be used as a reference point for regional agricultural
      extension employees where soil and/or plant N monitoring is lacking.

PMID- 24875748
TI  - Implementing a complex intervention to support personal recovery: a qualitative
      study nested within a cluster randomised controlled trial.
AB  - OBJECTIVE: To investigate staff and trainer perspectives on the barriers and
      facilitators to implementing a complex intervention to help staff support the
      recovery of service users with a primary diagnosis of psychosis in community
      mental health teams. DESIGN: Process evaluation nested within a cluster
      randomised controlled trial (RCT). PARTICIPANTS: 28 interviews with mental health
      care staff, 3 interviews with trainers, 4 focus groups with intervention teams
      and 28 written trainer reports. SETTING: 14 community-based mental health teams
      in two UK sites (one urban, one semi-rural) who received the intervention.
      RESULTS: The factors influencing the implementation of the intervention can be
      organised under two over-arching themes: Organisational readiness for change and
      Training effectiveness. Organisational readiness for change comprised three sub
      themes: NHS Trust readiness; Team readiness; and Practitioner readiness. Training
      effectiveness comprised three sub-themes: Engagement strategies; Delivery style
      and Modelling recovery principles. CONCLUSIONS: Three findings can inform future
      implementation and evaluation of complex interventions. First, the underlying
      intervention model predicted that three areas would be important for changing
      practice: staff skill development; intention to implement; and actual
      implementation behaviour. This study highlighted the importance of targeting the
      transition from practitioners' intent to implement to actual implementation
      behaviour, using experiential learning and target setting. Second, practitioners
      make inferences about organisational commitment by observing the allocation of
      resources, Knowledge Performance Indicators and service evaluation outcome
      measures. These need to be aligned with recovery values, principles and practice.
      Finally, we recommend the use of organisational readiness tools as an inclusion
      criteria for selecting both organisations and teams in cluster RCTs. We believe
      this would maximise the likelihood of adequate implementation and hence reduce
      waste in research expenditure. TRIAL REGISTRATION: Controlled-Trials.com
      ISRCTN02507940.

PMID- 24875749
TI  - Dietary acid load, insulin sensitivity and risk of type 2 diabetes in community
      dwelling older men.
AB  - AIMS/HYPOTHESIS: We tested the hypothesis that dietary acid load may increase the
      risk of type 2 diabetes, and studied the association between acid load and
      insulin sensitivity as a possible mechanism involved. METHODS: An observational
      survey with prospective follow-up including 911 non-diabetic Swedish men aged 70
      71 years was carried out. The gold standard euglycaemic-hyperinsulinaemic clamp
      technique and the OGTT were used to determine insulin sensitivity and beta cell
      function, respectively. Diabetes incidence was assessed during 18 years of follow
      up. Renal function was estimated from serum cystatin C concentrations. Dietary
      acid load was calculated as potential renal acid load (PRAL) and net endogenous
      acid production (NEAP) algorithms from 7 day food records. Adequate dietary
      reporters were identified by Goldberg cut-offs. RESULTS: PRAL and NEAP were not
      associated with insulin sensitivity or beta cell function. Underlying kidney
      function or consideration of dietary adequate reporters did not modify these null
      findings. During follow-up, 115 new cases of diabetes were validated. Neither
      PRAL nor NEAP was associated with diabetes incidence. CONCLUSIONS/INTERPRETATION:
      Our results do not support the hypothesis that dietary acid load influences
      insulin sensitivity, beta cell function or diabetes risk. Interventional studies
      modifying acid-base dietary intake are needed to further elucidate a possible
      role of acid load in the development of type 2 diabetes.

PMID- 24875750
TI  - The novel transferrin E592A variant impairs the diagnostics of congenital
      disorders of glycosylation.
AB  - BACKGROUND: The analysis of serum transferrin either by high-performance liquid
      chromatography (HPLC) or isoelectric focusing (IEF) is the standard diagnostic
      procedure in patients with the suspicion of a congenital disorder of
      glycosylation (CDG). Carbohydrate-deficient transferrin (CDT) is also analysed in
      monitoring programmes in cases of alcohol abuse. We report a novel transferrin
      variant that impairs the analysis using conventional methods and propose
      alternative forms of analysis. METHODS: Transferrin samples were analysed using
      HPLC, immunoprecipitation followed by SDS-PAGE and IEF. Neuraminidase treatment
      followed by conventional IEF and electrospray ionization time of flight mass
      spectrometry (ESI-TOF MS) were applied before sequencing of the transferrin gene
      was performed. RESULTS: The novel transferrin variant E592A, found both in
      homozygous and heterozygous form, causes an altered charge of the transferrin
      molecule, which changes the results of IEF and HPLC and mimics an increase in
      trisialo-transferrin. The change in charge can be detected either by
      neuraminidase digestion followed by IEF or by ESI-TOF MS. CONCLUSION:
      Conventional diagnostic methods for CDG are hindered by the novel transferrin
      E592A. Neuraminidase treatment followed by IEF and ESI-TOF MS can identify the
      mutation. The mutation appears to be functionally normal.

PMID- 24875751
TI  - Molecular characteristics of patients with glycosaminoglycan storage disorders in
      Russia.
AB  - BACKGROUND: The mucopolysaccharidoses (MPSs) are rare genetic disorders caused by
      mutations in lysosomal enzymes involved in the degradation of glycosaminoglycans
      (GAGs). In this study, we analyzed a total of 48 patients including MPSI (n=6),
      MPSII (n=18), MPSIIIA (n=11), MPSIVA (n=3), and MPSVI (n=10). METHODS: In MPS
      patients, urinary GAGs were colorimetrically assayed. Enzyme activity was
      quantified by colorimetric and fluorimetric assays. To find mutations, all IDUA,
      IDS, SGSH, GALNS, and ARSB exons and intronic flanks were sequenced. New
      mutations were functionally assessed by reconstructing mutant alleles with site
      directed mutagenesis followed with expression of wild-type and mutant genetic
      variants in CHO cells, measuring enzymatic activity, and Western blot analysis of
      protein expression of normal and mutated enzymes in cell lysates. RESULTS: A
      total of five novel mutations were found including p.Asn348Lys (IDUA) in MPSI,
      p.Tyr240Cys (GALNS) in MPSIVA, and three ARSB mutations (p.Gln110*,
      p.Asn262Lysfs*14, and pArg315*) in MPSVI patients. In case of mutations
      p.Asn348Lys, p.Asn262Lysfs*14, and p.Gln110*, no mutant protein was detected
      while activity of the mutant protein was <1% of that of the normal enzyme. For
      p.Tyr240Cys, a trace of mutant protein was observed with a remnant activity of
      3.6% of the wild-type GALNS activity. For pArg315*, a truncated 30-kDa protein
      that had 7.9% of activity of the normal ARSB was detected. CONCLUSIONS: These
      data further enrich our knowledge of the genetic background of MPSs.

PMID- 24875752
TI  - Low- and high-grade bladder cancer appraisal via serum-based proteomics approach.
AB  - OBJECTIVE: To address the shortcomings of urine cytology and cystoscopy for
      screening and grading of urinary bladder cancer (BC) we applied a serum-based
      proteomics approach as a surrogate tactic for rapid BC probing. METHODS: This
      study was performed on 90 sera samples comprising of low-grade (LG, n=33) and
      high-grade (HG, n=32) BC, and healthy controls (HC, n=25). Two-dimensional gel
      electrophoresis (2DE) tactic was executed to describe serum proteome. MALDI-TOF
      MS (MS) was used to identify the characteristics of aberrantly expressed proteins
      in 2DE and validated using Western blot (WB) and ELISA approach. Receiver
      operating characteristics (ROC) curve analysis was also performed to determine
      the clinical usefulness of these proteins to discriminate among LG, HG and HC
      cohorts. RESULTS: This comprehensive approach of 2DE, MS, WB and ELISA reveals
      five differentially expressed proteins. Among them two biomarkers (S100A8 and
      S100A9) were able to accurately (ROC, 0.946) distinguish 81% of BC (LG+HG) cases
      compared to HC with highest sensitivity and specificity. With a comparable
      tactic, two biomarkers (S100A8 and S100A4) were able to precisely (ROC, 0.941)
      discriminate 92% of LG cases from HG with utmost sensitivity and specificity.
      CONCLUSIONS: Serum proteomics probing appears to be an encouraging and least
      invasive tactic for screening and grading of BC.

PMID- 24875753
TI  - Human indoleamine 2,3-dioxygenase-2 has substrate specificity and inhibition
      characteristics distinct from those of indoleamine 2,3-dioxygenase-1.
AB  - Indoleamine 2,3-dioxygenase-2 (IDO2) is one of three enzymes (alongside
      tryptophan 2,3-dioxygenase and indoleamine 2,3-dioxygenase (IDO1)) that catalyse
      dioxygenation of L-tryptophan as the first step in the kynurenine pathway.
      Despite the reported expression of IDO2 in tumours, some fundamental
      characteristics of the enzyme, such as substrate specificity and inhibition
      selectivity, are still to be clearly defined. In this study, we report the
      kinetic and inhibition characteristics of recombinant human IDO2. Choosing from a
      series of likely IDO2 substrates, we screened 54 tryptophan derivatives and
      tryptophan-like molecules, and characterised the 8 with which the enzyme was most
      active. Specificity of IDO2 for the two isomers of 1-methyltryptophan was also
      evaluated and the findings compared with those obtained in other studies on IDO2
      and IDO1. Interestingly, IDO2 demonstrates behaviour distinct from that of IDO1
      in terms of substrate specificity and affinity, such that we have identified
      tryptophan derivatives that are mutually exclusive as substrates for IDO1 and
      IDO2. Our results support the idea that the antitumour activity of 1-Me-D-Trp is
      unlikely to be related with competitive inhibition of IDO2, and also imply that
      there are subtle differences in active site structure in the two enzymes that may
      be exploited in the development of specific inhibitors of these enzymes, a route
      which may prove important in defining their role(s) in cancer.

PMID- 24875754
TI  - Comparison between an independent midwifery program and a district hospital in
      rural Tanzania: observations regarding the treatment of female patients.
AB  - Tanzania faces a significant shortage of physicians. In light of this, nurse
      midwives have been critical in reducing maternal mortality in Tanzania in recent
      years. Despite the importance of both entities in providing health care to women
      in Tanzania, there have been few studies addressing the cultural competency of
      each entity. We shadowed and assisted both an independent nurse-midwife as well
      as physicians and nurse-midwives at a large district hospital in rural Tanzania.
      In this article we describe our observations regarding the treatment of female
      patients within the culture of an independent midwifery practice and at a large
      district hospital. 

PMID- 24875755
TI  - The failure of genomics in biology.
AB  - We live in the age of genomics and have discovered hundreds of thousands of genes
      of which we understand almost nothing: genomics has failed biology. We need to
      understand what genes do, something that we have stopped studying. Parasites are
      different from free-living species, and so they will have genes with novel
      functions, which we will only discover by studying this directly, not by doing
      genomics. 

PMID- 24875756
TI  - Folding graft copolymer with pendant drug segments for co-delivery of anticancer
      drugs.
AB  - A graft copolymer with pendant drug segments can fold into nanostructures in a
      protein folding-like manner. The graft copolymer is constructed by directly
      polymerizing gamma-camptothecin-glutamate N-carboxyanhydride (Glu(CPT)-NCA) on
      multiple sites of poly(ethylene glycol) (PEG)-based main chain via the ring open
      polymerization (ROP). The "purely" conjugated anticancer agent camptothecin (CPT)
      is hydrophobic and serves as the principal driving force during the folding
      process. When exposed to water, the obtained copolymer, together with doxorubicin
      (Dox), another anticancer agent, can fold into monodispersed nanocarriers (with a
      diameter of around 50 nm) for dual-drug delivery. Equipped with a PEG shell, the
      nanocarriers displayed good stability and can be internalized by a variety of
      cancer cell lines via the lipid raft and clathrin-mediated endocytotic pathway
      without premature leakage, which showed a high synergetic activity of CPT and Dox
      toward various cancer cells. In vivo study validated that the nanocarriers
      exhibited strong accumulation in tumor sites and showed a prominent anticancer
      activity against the lung cancer xenograft mice model compared with free drugs.

PMID- 24875758
TI  - Lentiviral MGMT(P140K)-mediated in vivo selection employing a ubiquitous
      chromatin opening element (A2UCOE) linked to a cellular promoter.
AB  - Notwithstanding recent successes, insertional mutagenesis as well as silencing
      and variegation of transgene expression still represent considerable obstacles to
      hematopoietic gene therapy. This also applies to O(6)-methylguanine DNA
      methyltransferase (MGMT)-mediated myeloprotection, a concept recently proven
      clinically effective in the context of glioblastoma therapy. To improve on this
      situation we here evaluate a SIN-lentiviral vector expressing the MGMT(P140K)
      cDNA from a combined A2UCOE/PGK-promoter. In a murine in vivo chemoselection
      model the A2UCOE.PGK.MGMT construct allowed for significant myeloprotection as
      well as robust and stable selection of transgenic hematopoietic cells. In
      contrast, only transient enrichment and severe myelotoxicity was observed for a
      PGK.MGMT control vector. Selection of A2UCOE.PGK.MGMT-transduced myeloid and
      lymphoid mature and progenitor cells was demonstrated in the peripheral blood,
      bone marrow, spleen, and thymus. Unlike the PGK and SFFV promoters used as
      controls, the A2UCOE.PGK promoter allowed for sustained vector copy number
      related transgene expression throughout the experiment indicating an increased
      resistance to silencing, which was further confirmed by CpG methylation studies
      of the PGK promoter. Thus, our data support a potential role of the
      A2UCOE.PGK.MGMT-vector in future MGMT-based myeloprotection and chemoselection
      strategies, and underlines the suitability of the A2UCOE element to stabilize
      lentiviral transgene expression in hematopoietic gene therapy.

PMID- 24875757
TI  - Hybrid polymeric micelles based on bioactive polypeptides as pH-responsive
      delivery systems against melanoma.
AB  - The bioactive polymer poly(L-glutamic acid)n-b-poly(D, L-lactic acid)m was
      synthesized and used to form doxorubicin-loaded hybrid polymeric micelles to
      treat melanoma. These polymers exhibited pH-responsive changes in conformation,
      which controlled the diverse functionalities of the micelles. During circulation,
      poly(L-glutamic acid)n-b-poly(D, L-lactic acid)m protected Tat peptides on the
      micelles from proteolysis. Under tumor-acidic conditions, polymers with shorter
      poly(l-glutamic acid) blocks underwent a conformational change to form channels
      that accelerated the release of doxorubicin. The conformational change also
      exposed the Tat peptides to tumor cells, thereby promoting cellular
      internalization of the micelles. Enhanced cellular uptake of the micelles induced
      significant apoptosis of A375 melanoma cells in tumor-acidic conditions. In vivo
      studies demonstrated that the micelles with shorter poly(L-glutamic acid) blocks
      could effectively accumulate in tumor tissues, suppress tumor growth and help
      maintain the body weight of tumor-bearing mice. However, micelles with longer
      poly(l-glutamic acid) blocks did not undergo a conformational change under acidic
      conditions and performed poorly in both in vitro and in vivo evaluations. Our
      work provides a strategy for applying bioactive polymers to the rational
      construction of pH-responsive delivery systems for solid tumors and lends insight
      into possible conformational effects on the bioactivity of drug carriers.

PMID- 24875759
TI  - Direct cytosolic siRNA delivery by reconstituted high density lipoprotein for
      target-specific therapy of tumor angiogenesis.
AB  - We described here the mechanisms by which small interfering RNA (siRNA) molecules
      incorporated in reconstituted high density lipoprotein (rHDL) were efficiently
      transferred into the cytoplasm of cells to perform target-specific therapy of
      tumor angiogenesis. Using fluorescent-tagged apolipoprotein A-I (apoA-I) and
      cholesterol-conjugated siRNA (Chol-siRNA), it was confirmed with FACS and
      confocal microscopic measurements that Chol-siRNA-loaded rHDL nanoparticles
      (rHDL/Chol-siRNA complexes) were successfully established and apoA-I certainly
      was attached to the surface of Chol-siRNA-loaded lipoplexes (Lipos/Chol-siRNA
      complexes). Stably assembled rHDL/Chol-siRNA complexes demonstrated proper
      nanosize, quasi-spherical shape and improved nuclease protection over naked Chol
      siRNA. It was also interesting to note that rHDL provided a highly effective
      approach to transfer Chol-siRNA across the membrane directly into the cytoplasm
      via the scavenger receptor BI (SR-BI)-mediated non-endocytotic mechanism, thereby
      bypassing endo-lysosomal trapping. We also showed clear evidence that the in
      vitro implementation of rHDL for Chol-siRNA-VEGF (Chol-siRNA targeting vascular
      endothelial growth factor gene) delivery markedly promoted RNA interference
      (RNAi)-mediated degradation of VEGF mRNA, resulting in down-regulation of
      secreted VEGF protein. In vivo fluorescence imaging indicated that near-infrared
      (NIR) dye Cy5 labeled Chol-siRNA-loaded rHDL nanoparticles (rHDL/Cy5-Chol-siRNA
      complexes) displayed long circulation time, SR-BI positive tumor-selective
      targeting, and efficient cytosolic delivery capabilities. Furthermore,
      intravenous administration of Chol-siRNA-VEGF-loaded rHDL nanoparticles
      (rHDL/Chol-siRNA-VEGF complexes) significantly enhanced anti-tumor efficacy
      against breast cancer, decreased VEGF expression level, and inhibited formation
      of intratumoral microvessels at the tumor tissue. It was concluded that rHDL
      possessed therapeutic potential and versatility in mediating Chol-siRNA-VEGF
      direct cytosolic delivery for target-specific anti-angiogenic therapy in breast
      cancer.

PMID- 24875760
TI  - Kinetics of oxygen uptake by cells potentially used in a tissue engineered
      trachea.
AB  - Synthetic polymer scaffold seeded with autologous cells have a clinical
      translational potential. A rational design oriented to clinical applications must
      ensure an efficient mass transfer of nutrients as a function of specific
      metabolic rates, especially for precariously vascularized tissues grown in vitro
      or integrated in vivo. In this work, luminescence lifetime-based sensors were
      used to provide accurate, extensive and non-invasive measurements of the oxygen
      uptake rate for human mesenchymal stem cells (hMSCs), tracheal epithelial cells
      (hTEpiCs) and human chondrocytes (hCCs) within a range of 2-40% O2 partial
      pressure. Estimated Michaelis-Menten parameters were: V(max) = 0.099 pmol/cell?h
      and K(M) = 2.12 * 10(-7) mol/cm(3) for hMSCs, V(max) = 1.23 pmol/cell?h and K(M)
      = 2.14 * 10(-7) mol/cm(3) for hTEpiCs, V(max) = 0.515 pmol/cell?h and K(M) = 1.65
      * 10(-7) mol/cm(3) for hCCs. Kinetics data served as an input to a preliminary
      computational simulation of cell culture on a poly-ethylene terephthalate (PET)
      tracheal scaffold obtaining an efficient mass transfer at cell density of 10(6)
      cell/cm(3). Oxygen concentration affected the glucose uptake and lactate
      production rates of cells that adapted their metabolism according to energy
      demand in hypoxic and normoxic conditions.

PMID- 24875762
TI  - Tenogenic differentiation of human induced pluripotent stem cell-derived
      mesenchymal stem cells dictated by properties of braided submicron fibrous
      scaffolds.
AB  - Tendon and ligament (T/L) engineering is a growing area of research with
      potential to address the inadequacies of current T/L defect treatments. Our group
      previously developed braided submicron fibrous scaffolds (BSMFSs) and
      demonstrated the viability of BSMFSs for T/L tissue engineering. The objective of
      this study was to investigate the effect of fiber chemistry and braiding angle on
      BSMFS mechanical properties and in turn, tenogenic differentiation of human
      induced pluripotent stem cell-derived mesenchymal stem cells (hiPSC-MSCs) seeded
      on BSMFSs subjected to cyclic tensile stimulation in the absence of tenogenic
      medium. By varying fiber chemistry and/or braiding angle, BSMFSs with a range of
      mechanical properties were produced. We found that fiber chemistry dictated cell
      adhesion while braiding angle dictated the tissue-specific lineage commitment of
      hiPSC-MSCs. Scaffolds braided with large angles better supported hiPSC-MSC
      tenogenic differentiation as evidenced by the production of T/L-associated
      markers, downregulation of osteogenic markers, and expression of fibroblast-like,
      spindle cell morphology compared to scaffolds braided with small angles. Our
      results demonstrate the importance of substrate properties and mechanical
      stimulation on tenogenic differentiation. These results also demonstrate the
      versatility of BSMFSs and the potential of hiPSC-MSCs for T/L tissue engineering.

PMID- 24875761
TI  - Preserved bioactivity and tunable release of a SDF1-GPVI bi-specific protein
      using photo-crosslinked PEGda hydrogels.
AB  - Chemokine-induced stem cell recruitment is a promising strategy for post
      myocardial infarction treatment. Injection of stromal cell-derived factor 1
      (SDF1) has been shown to attract bone marrow-derived progenitor cells (BMPCs)
      from the blood that have the potential to differentiate into cardiovascular
      cells, which support angiogenesis, enabling the improvement of myocardial
      function. SDF1-GPVI bi-specific protein contains a glycoprotein VI (GPVI)-domain
      that serves as an anchor for collagen type I (Col I) and III, which are exposed
      in the wall of injured vasculature. In this study, we generated a cytocompatible
      hydrogel via photo-crosslinking of poly(ethylene glycol) diacrylate that serves
      as a reservoir for SDF1-GPVI. Controlled and sustained release of SDF1-GPVI was
      demonstrated over a period of 7 days. Release features were modifiable depending
      on the degree of the crosslinking density. Functionality of the GPVI-domain was
      investigated using a GPVI-binding ELISA to Col I. Activity of the SDF1-domain was
      tested for its CXCR4 binding potential. Preserved functionality of SDF1-GPVI bi
      specific protein after photo-crosslinking and controllable release was
      successfully demonstrated in vitro supporting the implementation of this drug
      delivery system as a powerful tool for therapeutic protein delivery in the
      treatment of cardiovascular ischemic disease.

PMID- 24875763
TI  - Anti-inflammatory effects of three-dimensional graphene foams cultured with
      microglial cells.
AB  - One of the key goals in nerve tissue engineering is to develop new materials
      which cause less or no neuroinflammation. Despite the rapid advances of using
      graphene as a neural interface material, it still remains unknown whether
      graphene could provoke neuroinflammation or not, and whether and how the
      topographical features of graphene influence the neuroinflammation induction. By
      immunofluorescence, Elisa technique, western blot, scanning electron microscope
      (SEM) methods, we investigated the pro- and/or anti-inflammatory responses of
      microglia in the graphene films (2D-graphene) or graphene foams (3D-graphene)
      culturing systems. Furthermore, the growth situations of the neural stem cells
      (NSCs) in the conditioned culture medium produced in the graphene substrates were
      evaluated. The results show that: 1) neither 2D nor 3D graphene induced distinct
      neuroinflammation when compared to the tissue culture polystyrene (TCPS)
      substrates; 2) the topographical structures of the graphene might affect the
      material/cell interactions, leading to disparate effects on lipopolysaccharide
      (LPS)-induced neuroinflammation; 3) 3D graphene exhibited a remarkable capability
      of rescuing LPS-induced neuroinflammation probably through the restriction of
      microglia morphological transformation by the unique topographical features on
      the surface, showing the ability of anti-inflammation against external insults,
      while 2D graphene failed to. These results provide insights into the diverse
      biological effects of the material's topographical structures and open new
      opportunity for the applications of graphene in neuroscience. 

PMID- 24875764
TI  - An aptamer ligand based liposomal nanocarrier system that targets tumor
      endothelial cells.
AB  - The objective of this study was to construct our recently developed aptamer
      modified targeted liposome nano-carrier (Apt-PEG-LPs) system to target primary
      cultured mouse tumor endothelial cells (mTEC), both in vitro and in vivo. We
      first synthesized an aptamer-polyethylene glycol 2000-distearoyl
      phosphoethanolamine (Apt-PEG2000-DSPE). The conjugation of the Apt-PEG2000-DSPE
      was confirmed by MALDI-TOF mass spectroscopy. A lipid hydration method was used
      to prepare Apt-PEG-LPs, in which the outer surface of the PEG-spacer was
      decorated with the aptamer. Apt-PEG-LPs were significantly taken up by mTECs.
      Cellular uptake capacity was observed both quantitatively and qualitatively using
      spectrofluorometry, and confocal laser scanning microscopy (CLSM), respectively.
      In examining the extent of localization of aptamer-modified liposomes that
      entered the cells, approximately 39% of the Apt-PEG-LPs were not co-localized
      with lysotracker, indicating that they had escaped from endosomes. The uptake
      route involved a receptor mediated pathway, followed by clathrin mediated
      endocytosis. This Apt-PEG-LP was also applied for in vivo research whether this
      system could target tumor endothelial cells. Apt-PEG-LP and PEG5000-DSPE modified
      Apt-PEG-LP (Apt/PEG5000-LP) were investigated by human renal cell carcinoma (OS
      RC-2 cells) inoculating mice using CLSM. Apt-PEG-LP and Apt/PEG5000-LP showed
      higher accumulation on tumor vasculature compared to PEG-LP and the co
      localization efficacy of Apt-PEG-LP and Apt/PEG5000-LP on TEC were quantified 16%
      and 25% respectively, which was also better than PEG-LP (3%). The findings
      suggest that this system is considerable promise for targeting tumor endothelial
      cells to deliver drugs or genes in vitro and in vivo.

PMID- 24875766
TI  - Interaction between viral RNA silencing suppressors and host factors in plant
      immunity.
AB  - To elucidate events in the molecular arms race between the host and pathogen in
      evaluating plant immunity, a zigzag model is useful for uncovering aspects common
      to different host-pathogen interactions. By analogy of the steps in virus-host
      interactions with the steps in the standard zigzag model outlined in recent
      papers, we may regard RNA silencing as pattern-triggered immunity (PTI) against
      viruses, RNA silencing suppressors (RSSs) as effectors to overcome host RNA
      silencing and resistance gene (R-gene)-mediated defense as effector-triggered
      immunity (ETI) recognizing RSSs as avirulence proteins. However, because the
      standard zigzag model does not fully apply to some unique aspects in the
      interactions between a plant host and virus, we here defined a model especially
      designed for viruses. Although we simplified the phenomena involved in the virus
      host interactions in the model, certain specific interactive steps can be
      explained by integrating additional host factors into the model. These host
      factors are thought to play an important role in maintaining the efficacy of the
      various steps in the main pathway of defense against viruses in this model for
      virus-plant interactions. For example, we propose candidates that may interact
      with viral RSSs to induce the resistance response. 

PMID- 24875767
TI  - Staying in touch: mechanical signals in plant-microbe interactions.
AB  - Mechanical stimulations play a significant role in the day to day existence of
      plants. Plants exhibit varied responses depending on the nature and intensity of
      these stimuli. In this review, we present recent literature on the responses of
      plants to mechanical stimuli, focusing primarily on those exerted during plant
      microbe interactions. We discuss how microbes are able to apply mechanical
      stimuli on plants and how some plant responses to pathogenic and symbiotic
      microbes present striking similarities with responses to mechanical stimuli
      applied, for instance, using micro-needles. We hypothesize that appropriate
      responses of plants to pathogenic and symbiotic microbes may require a tight
      integration of both chemical and mechanical stimulations exerted by these
      microbes. 

PMID- 24875768
TI  - Synthesis, structure-activity relationships and biological activity of new isatin
      derivatives as tyrosinase inhibitors.
AB  - A newly series of isatin derivatives (6a-t) containing alkyl/aryl urea groups
      were synthesized and their inhibitory effects on the diphenolase activity of
      banana tyrosinase were evaluated. Tyrosinase was purified from banana on an
      affinity gel comprised of Sepharose 4B-L-tyrosine-p-aminobenzoic acid. The
      results showed that all the synthesized compounds inhibited the tyrosinase enzyme
      activity. Among them, 1-(2,3-dioxoindolin-5-yl)-3-(4-nitrophenyl)urea (6l) was
      found to be most active compound (Ki = 24.96 uM). The inhibition kinetics was
      analysed by Lineweaver-Burk double reciprocal plots. It revealed that compound 6l
      was a competitive inhibitor. According to results of structure-activity
      relationship, generally, the compounds electron-donating group bonded to the
      phenyl ring have higher inhibitory activity against tyrosinase than halogen group
      bonded to the phenyl ring. The inhibitory activities of alkyl urea substituted
      compounds decreased with increasing carbon number of the alkyl groups at urea
      moiety. The halogen series at the para position of the phenyl ring showed a
      qualitative relationship for higher inhibitory activity with increasing size and
      polarizability. HOMOLUMO energy levels and dipole moments of some selected
      compounds (6a, 6d, 6h, 6l and 6o) were also calculated by Gaussian software.

PMID- 24875765
TI  - Gene delivery from supercharged coiled-coil protein and cationic lipid hybrid
      complex.
AB  - A lipoproteoplex comprised of an engineered supercharged coiled-coil protein
      (CSP) bearing multiple arginines and the cationic lipid formulation FuGENE HD
      (FG) was developed for effective condensation and delivery of nucleic acids. The
      CSP was able to maintain helical structure and self-assembly properties while
      exhibiting binding to plasmid DNA. The ternary CSP.DNA(8:1).FG lipoproteoplex
      complex demonstrated enhanced transfection of beta-galactosidase DNA into MC3T3
      E1 mouse preosteoblasts. The lipoproteoplexes showed significant increases in
      transfection efficiency when compared to conventional FG and an mTat.FG
      lipopolyplex with a 6- and 2.5-fold increase in transfection, respectively. The
      CSP.DNA(8:1).FG lipoproteoplex assembled into spherical particles with a net
      positive surface charge, enabling efficient gene delivery. These results support
      the application of lipoproteoplexes with protein engineered CSP for non-viral
      gene delivery. 

PMID- 24875770
TI  - Subchronic and mild social defeat stress accelerates food intake and body weight
      gain with polydipsia-like features in mice.
AB  - Development and characterization of animal models of depression are essential for
      fully understanding the pathogenesis of depression in humans. We made and
      analyzed a mouse model exhibiting social deficit and hyperphagia-like behavior
      using a subchronic and mild social defeat stress (sCSDS) paradigm. The body
      weight, food and water intake of mice were monitored during a test period, and
      their behaviors and serum components were analyzed at two stages: immediately
      after the sCSDS period and 1 month after the sCSDS. The body weight and food
      intake of defeated mice were significantly higher than control mice at the sCSDS
      period, and these differences were sustained until 1 month after the sCSDS,
      whereas the water intake of defeated mice was significantly higher than control
      mice for the period of sCSDS only. Behavioral analyses revealed that the defeated
      mice exhibit significant social aversion to unfamiliar mice in a social
      interaction test and a trend of anxiety-like behavior in an elevated-plus maze
      test. Possibly due to polydipsia-like symptoms, defeated mice had significantly
      lower levels of albumin and blood urea nitrogen than control mice immediately
      after the sCSDS period but not at 1 month after sCSDS. The present study revealed
      that our sCSDS mice keep much more water in their body than control mice. This
      study reports the first step toward an understanding of the mechanisms of stress
      induced overhydration, over-eating and resultant weight gain. 

PMID- 24875769
TI  - Maintenance of dominance status is necessary for resistance to social defeat
      stress in Syrian hamsters.
AB  - Resilience is an active process that involves a discrete set of neural substrates
      and cellular mechanisms and enables individuals to avoid some of the negative
      consequences of extreme stress. We have previously shown that dominant
      individuals show less stress-induced changes in behavior compared to subordinates
      using a conditioned defeat model in male Syrian hamsters (Mesocricetus auratus).
      To rule out pre-existing differences between dominants and subordinates, we
      examined whether 14 days of dominance experience is required to reduce the
      conditioned defeat response and whether the development of conditioned defeat
      resistance correlates with defeat-induced neural activation in select brain
      regions. We paired hamsters in daily 5-min aggressive encounters for 1, 7, or 14
      days and then exposed animals to 3, 5-min social defeat episodes. The next day
      animals received conditioned defeat testing which involved a 5-min social
      interaction test with a non-aggressive intruder. In separate animals brains were
      collected after social defeat for c-Fos immunohistochemistry. We found that 14
      day dominants showed a decreased conditioned defeat response compared to 14-day
      subordinates and controls, while 1-day and 7-day dominants did not differ from
      their subordinate counterparts. Also, the duration of dominance relationship was
      associated with distinct patterns of defeat-induced neural activation such that
      only 14-day dominants showed elevated c-Fos immunoreactivity in the ventral
      medial prefrontal cortex, medial amygdala, and lateral portions of the ventral
      medial hypothalamus. Our data suggest that resistance to social stress develops
      during the maintenance of dominance relationships and is associated with
      experience-dependent neural plasticity in select brain regions. 

PMID- 24875771
TI  - Functional interaction and cross-tolerance between ethanol and Delta9-THC:
      possible modulation by mouse cerebellar adenosinergic A1/GABAergic-A receptors.
AB  - We have previously shown a functional motor interaction between ethanol and
      Delta(9)-tetrahydrocannabinol (Delta(9)-THC) that involved cerebellar
      adenosinergic A1 and GABAergic A receptor modulation. We now report the
      development of cross-tolerance between intracerebellar Delta(9)-THC and
      intraperitoneal ethanol using ataxia as the test response in male CD-1 mice. The
      drugs [Delta(9)-THC (20 MUg), N(6)-cyclohexyladenosine, CHA (12 ng), muscimol (20
      ng)] used in the study were directly microinfused stereotaxically via guide
      cannulas into the cerebellum except ethanol. Delta(9)-THC, infused once daily for
      5 days followed 16 h after the last infusion by acute ethanol (2g/kg) and Rotorod
      evaluation, virtually abolished ethanol ataxia indicating development of cross
      tolerance. The cross-tolerance was also observed when the order of ethanol and
      Delta(9)-THC treatment was reversed, i.e., ethanol injected once daily for 5 days
      followed 16 h after the last ethanol injection by Delta(9)-THC infusion. The
      cross-tolerance appeared within 24-48 h, lasted over 72 h and was maximal in 5
      day ethanol/Delta(9)-THC-treated animals. Finally, tolerance in chronic
      ethanol/Delta(9)-THC/-treated animals developed not only to ethanol/Delta(9)-THC
      induced ataxia, respectively, but also to the ataxia potentiating effect of CHA
      and muscimol, indicating modulation by cerebellar adenosinergic A1 and GABAA
      receptors. A practical implication of these results could be that marijuana
      smokers may experience little or no negative effects such as ataxia following
      alcohol consumption. Clinically, such antagonism of ethanol-induced ataxia can be
      observed in marijuana users thereby encouraging more alcohol consumption and thus
      may represent a risk factor for the development of alcoholism in this segment of
      population.

PMID- 24875772
TI  - Evidence for anxiolytic effects of acute caffeine on anxiety-related behavior in
      male and female rats tested with and without bright light.
AB  - Male and female PVG/c rats were observed in an open field (OF) and an elevated
      plus maze (EPM) either with or without a bright light stressor (600-692 lx)
      following an intraperitoneal injection of saline, 25 or 50mg/kg of caffeine. One
      week later, the same rats were observed under the same drug and lighting
      conditions but in the opposite apparatus to that experienced earlier. Either the
      higher or both doses of caffeine decreased anxiety as indicated by increased OF
      rearing and decreased grooming, immobility and corner occupancy (in the presence
      of bright light). A similar interpretation applied to caffeine-related increased
      entries into and observations in the EPM open arms for males only, and increased
      entries into the open arms for females alone in the presence of bright light.
      Bright light increased anxiety as shown by longer latencies of emergence into the
      OF and decreased ambulation and, for males only, decreased center occupancy and
      increased corner occupancy. Fewer entries into the open arms in the presence of
      bright light for females only also suggested heightened anxiety. Apart from one
      OF and one EPM measure, bright light did not appear to markedly influence the
      effects of caffeine which were concluded to be primarily anxiolytic, with males
      being more affected than females. Although the central mechanisms responsible for
      caffeine's anxiolytic action remain to be established, it is possible that
      antagonism of A2A adenosine receptors might somehow be involved.

PMID- 24875773
TI  - Inhibition of propofol on single neuron and neuronal ensemble activity in
      prefrontal cortex of rats during working memory task.
AB  - Working memory (WM) refers to the temporary storage and manipulation of
      information necessary for performance of complex cognitive tasks. There is a
      growing interest in whether and how propofol anesthesia inhibits WM function. The
      aim of this study is to investigate the possible inhibition mechanism of propofol
      anesthesia from the view of single neuron and neuronal ensemble activities. Adult
      SD rats were randomly divided into two groups: propofol group (0.9 mg kg(-1)min(
      1), 2h via a tail vein catheter) and control group. All the rats were tested for
      working memory performances in a Y-maze-rewarded alternation task (a task of
      delayed non-matched-to-sample) at 24, 48, 72 h after propofol anesthesia, and the
      behavior results of WM tasks were recorded at the same time. Spatio-temporal
      trains of action potentials were obtained from the original signals. Single
      neuron activity was characterized by peri-event time histograms analysis and
      neuron ensemble activities were characterized by Granger causality to describe
      the interactions within the neuron ensemble. The results show that: comparing
      with the control group, the percentage of neurons excited and related to WM was
      significantly decreased (p<0.01 in 24h, p<0.05 in 48 h); the interactions within
      neuron ensemble were significantly weakened (p<0.01 in 24h, p<0.05 in 48 h),
      whereas no significant difference in 72 h (p>0.05), which were consistent with
      the behavior results. These findings could lead to improved understanding of the
      mechanism of anesthesia inhibition on WM functions from the view of single neuron
      activity and neuron ensemble interactions.

PMID- 24875774
TI  - Direct observation of half-metallicity in the Heusler compound Co2MnSi.
AB  - Ferromagnetic thin films of Heusler compounds are highly relevant for spintronic
      applications owing to their predicted half-metallicity, that is, 100% spin
      polarization at the Fermi energy. However, experimental evidence for this
      property is scarce. Here we investigate epitaxial thin films of the compound
      Co2MnSi in situ by ultraviolet-photoemission spectroscopy, taking advantage of a
      novel multi-channel spin filter. By this surface sensitive method, an
      exceptionally large spin polarization of (93(-11)(+7)) % at room temperature is
      observed directly. As a more bulk sensitive method, additional ex situ spin
      integrated high energy X-ray photoemission spectroscopy experiments are
      performed. All experimental results are compared with advanced band structure and
      photoemission calculations which include surface effects. Excellent agreement is
      obtained with calculations, which show a highly spin polarized bulk-like surface
      resonance ingrained in a half metallic bulk band structure.

PMID- 24875777
TI  - Theory of mind understanding and empathic behavior in children with autism
      spectrum disorders.
AB  - This paper begins with a review of past research on theory of mind and empathy in
      children with ASD. Using varied operational definitions of empathy ranging from
      physiological heart rate through story vignettes to reports by privileged
      observers (e.g., teachers) of children's empathic behavior, results of previous
      studies are limited and contradictory. Thus new evidence is needed to answer two
      key questions: Are children with ASD less empathic than typically developing
      children? Do individual differences in theory of mind (ToM) understanding among
      children with ASD predict differences in their behavioral empathy? An original
      empirical study of 76 children aged 3-12 years (37 with ASD; 39 with typical
      development) addressed these. Results showed that children with ASD were
      significantly less empathic, according to their teachers, than typically
      developing children. However, this was not because of their slower ToM
      development. Findings showed equally clearly that ToM understanding was unrelated
      to empathy in children with ASD. The same was true for typically developing
      children once age and verbal maturity were controlled. Indeed, even the subgroup
      of older children with ASD in the sample who passed false belief tests were
      significantly less empathic than younger preschoolers who failed them. 

PMID- 24875778
TI  - Alterations of visual and auditory evoked potentials in fragile X syndrome.
AB  - BACKGROUND: Fragile X Syndrome (FXS) is the most common monogenic form of
      intellectual disability and one of the few known monogenic causes of autism. It
      is caused by a trinucleotide repeat expansion in the FMR1 ('Fragile X Mental
      Retardation 1') gene, which prevents expression of the 'Fragile X Mental
      Retardation Protein' (FMRP). In FXS, the absence of FMRP leads to altered
      structural and functional development of the synapse, while preventing activity
      based synapse maturation and synaptic pruning, which are essential for normal
      brain development and cognitive development. Possible impairments in information
      processing can be non-invasively investigated using electrophysiology. METHODS:
      We compared auditory (AEP) and visual (VEP) evoked potentials in twelve
      adolescents and young adults (10-22 years) affected by FXS to healthy controls
      matched by chronological age (N=12) and developmental age of cognitive
      functioning (N=9; 5-7 years), using analysis of variance. RESULTS: In the visual
      modality, the N70 and N2 amplitude have been found increased in FXS in comparison
      to the chronological, but not the developmental control group at occipital sites,
      whereas in the auditory modality N1, P2 and N2 amplitude as well as N2 latency
      have been found increased in FXS, relative to both chronological and
      developmental control groups at mid-central sites. CONCLUSIONS: The AEP/VEP
      profile suggests disruptions in sensory processing specific to FXS that exceed
      immaturity of physiological activity. In addition, the auditory modality seems to
      be more affected than the visual modality. Results are discussed in light of
      possible underlying neuronal mechanisms, including deficits in synaptic pruning
      and neuronal inhibition that might account for a hyperreactive nervous system in
      FXS.

PMID- 24875776
TI  - The impact of population demography and selection on the genetic architecture of
      complex traits.
AB  - Population genetic studies have found evidence for dramatic population growth in
      recent human history. It is unclear how this recent population growth, combined
      with the effects of negative natural selection, has affected patterns of
      deleterious variation, as well as the number, frequency, and effect sizes of
      mutations that contribute risk to complex traits. Because researchers are
      performing exome sequencing studies aimed at uncovering the role of low-frequency
      variants in the risk of complex traits, this topic is of critical importance.
      Here I use simulations under population genetic models where a proportion of the
      heritability of the trait is accounted for by mutations in a subset of the exome.
      I show that recent population growth increases the proportion of nonsynonymous
      variants segregating in the population, but does not affect the genetic load
      relative to a population that did not expand. Under a model where a mutation's
      effect on a trait is correlated with its effect on fitness, rare variants explain
      a greater portion of the additive genetic variance of the trait in a population
      that has recently expanded than in a population that did not recently expand.
      Further, when using a single-marker test, for a given false-positive rate and
      sample size, recent population growth decreases the expected number of
      significant associations with the trait relative to the number detected in a
      population that did not expand. However, in a model where there is no correlation
      between a mutation's effect on fitness and the effect on the trait, common
      variants account for much of the additive genetic variance, regardless of
      demography. Moreover, here demography does not affect the number of significant
      associations detected. These findings suggest recent population history may be an
      important factor influencing the power of association tests and in accounting for
      the missing heritability of certain complex traits.

PMID- 24875779
TI  - Noncirrhotic intrahepatic portal hypertension: towards a unifying definition and
      etiology.

PMID- 24875780
TI  - Outcome of Medically Versus Surgically Treated Patients With Chronic
      Thromboembolic Pulmonary Hypertension.
AB  - Chronic thromboembolic pulmonary hypertension (CTEPH) is an ominous disease
      leading to progressive right heart failure. Selected patients can be treated by
      pulmonary endarterectomy (PEA). We assessed long-term clinical outcome of
      patients with CTEPH who underwent PEA and patients who remained on medical
      treatment alone. A total of 112 consecutive patients with CTEPH referred between
      1998 and 2008 to one center were followed for a mean of 35 (range 0-128) months
      after diagnosis. All the patients had advanced pulmonary hypertension at
      baseline. The operated group had higher World Health Organization functional
      class compared to the nonoperated group. No other differences in hemodynamic,
      echocardiographic, or biochemical parameters were observed at baseline. Despite
      the perioperative mortality rate of 9.1%, patients who underwent PEA had
      significantly lower long-term mortality compared to nonoperated patients (12.7%
      vs 34.8%; P = .003), and PEA survivors showed sustained clinical improvement. All
      efforts should be undertaken to perform PEA in all patients with operable CTEPH. 

PMID- 24875775
TI  - The inflammasome pyrin contributes to pertussis toxin-induced IL-1beta synthesis,
      neutrophil intravascular crawling and autoimmune encephalomyelitis.
AB  - Microbial agents can aggravate inflammatory diseases, such as multiple sclerosis
      (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). An
      example is pertussis toxin (PTX), a bacterial virulence factor commonly used as
      an adjuvant to promote EAE, but whose mechanism of action is unclear. We have
      reported that PTX triggers an IL-6-mediated signaling cascade that increases the
      number of leukocytes that patrol the vasculature by crawling on its luminal
      surface. In the present study, we examined this response in mice lacking either
      TLR4 or inflammasome components and using enzymatically active and inactive forms
      of PTX. Our results indicate that PTX, through its ADP-ribosyltransferase
      activity, induces two series of events upstream of IL-6: 1) the activation of
      TLR4 signaling in myeloid cells, leading to pro-IL-1beta synthesis; and 2) the
      formation of a pyrin-dependent inflammasome that cleaves pro-IL-1beta into its
      active form. In turn, IL-1beta stimulates nearby stromal cells to secrete IL-6,
      which is known to induce vascular changes required for leukocyte adhesion.
      Without pyrin, PTX does not induce neutrophil adhesion to cerebral capillaries
      and is less effective at inducing EAE in transgenic mice with encephalitogenic T
      lymphocytes. This study identifies the first microbial molecule that activates
      pyrin, a mechanism by which infections may influence MS and a potential
      therapeutic target for immune disorders. 

PMID- 24875782
TI  - Can the increasing number of newly developed leucine-rich repeat kinase 2
      inhibitors validate or invalidate a potential disease-modifying therapeutic
      approach for Parkinson's disease?
AB  - Leucine-rich repeat kinase 2 (LRRK2) is considered an attractive therapeutic
      target for potential disease-modifying treatment of Parkinson's disease (PD).
      Both genetic and cell biological evidence have contributed to the hypothesis that
      LRRK2 kinase inhibition may have therapeutic potential in PD. This hypothesis was
      widely translated in drug discovery programs as illustrated by the growing number
      of patents covering newly discovered LRRK2 kinase inhibitors and emanating from
      at least 20 different public and private research organizations. With work still
      under way, this research shows the feasibility of developing potent, selective
      and brain permeable LRRK2 kinase inhibitors. The growing availability of these
      pharmacological tools should contribute to filling in the gaps in our knowledge
      on the safety and efficacy of LRRK2 kinase inhibition and validate/invalidate
      this therapeutic strategy for further development. Validation criteria should
      include a lack of toxic effects following long-term treatment with inhibitors as
      well as confirmation of target engagement in cells and animal models leading to
      improvement of pathological features in phenotypic assays. The state of
      advancement of the field of LRRK2 is such that existing biological tools and
      expertise can be combined with the increasing number of available LRRK2 kinase
      inhibitors to address these key issues. 

PMID- 24875781
TI  - Major bleeding with dabigatran and rivaroxaban in patients with atrial
      fibrillation: a real-world setting.
AB  - BACKGROUND: Although the rate of bleeding among patients with atrial fibrillation
      (AF) taking novel oral anticoagulants in randomized controlled trials is
      described, the rate of bleeding with "real-world" use is uncertain. METHODS: We
      conducted a retrospective electronic medical record interrogation and subsequent
      chart review among patients within Intermountain Healthcare between October 2010
      and November 2012. Patients were included if they had a diagnosis of AF and were
      receiving either dabigatran or rivaroxaban. Rates of major bleeding were
      calculated. RESULTS: Among 2579 patients, 13 (0.5%) experienced major bleeding
      (95% confidence interval [CI] 0.23-0.77), 5 (0.19%) experienced intracranial
      hemorrhage (95% CI 0.02-0.36), and 2 (0.08%) experienced fatal bleeding. Of the
      13 patients experiencing a major bleed, 8 (61.5%) would have been excluded from
      the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) and
      Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K
      Antagonism for prevention of Stroke and Embolism Trial in Atrial Fibrillation
      (ROCKET AF) clinical trials. CONCLUSION: We observed a rate of major bleeding
      similar to that reported in randomized clinical trials among patients with AF
      prescribed dabigatran or rivaroxaban.

PMID- 24875783
TI  - The continual reassessment method for multiple toxicity grades: a bayesian model
      selection approach.
AB  - Grade information has been considered in Yuan et al. (2007) wherein they proposed
      a Quasi-CRM method to incorporate the grade toxicity information in phase I
      trials. A potential problem with the Quasi-CRM model is that the choice of
      skeleton may dramatically vary the performance of the CRM model, which results in
      similar consequences for the Quasi-CRM model. In this paper, we propose a new
      model by utilizing bayesian model selection approach--Robust Quasi-CRM model--to
      tackle the above-mentioned pitfall with the Quasi-CRM model. The Robust Quasi-CRM
      model literally inherits the BMA-CRM model proposed by Yin and Yuan (2009) to
      consider a parallel of skeletons for Quasi-CRM. The superior performance of
      Robust Quasi-CRM model was demonstrated by extensive simulation studies. We
      conclude that the proposed method can be freely used in real practice.

PMID- 24875784
TI  - Special issue.

PMID- 24875785
TI  - Studying the role of synchronized and chaotic spiking neural ensembles in neural
      information processing.
AB  - The brain is characterized by performing many diverse processing tasks ranging
      from elaborate processes such as pattern recognition, memory or decision making
      to more simple functionalities such as linear filtering in image processing.
      Understanding the mechanisms by which the brain is able to produce such a
      different range of cortical operations remains a fundamental problem in
      neuroscience. Here we show a study about which processes are related to chaotic
      and synchronized states based on the study of in-silico implementation of
      Stochastic Spiking Neural Networks (SSNN). The measurements obtained reveal that
      chaotic neural ensembles are excellent transmission and convolution systems since
      mutual information between signals is minimized. At the same time, synchronized
      cells (that can be understood as ordered states of the brain) can be associated
      to more complex nonlinear computations. In this sense, we experimentally show
      that complex and quick pattern recognition processes arise when both synchronized
      and chaotic states are mixed. These measurements are in accordance with in vivo
      observations related to the role of neural synchrony in pattern recognition and
      to the speed of the real biological process. We also suggest that the high-level
      adaptive mechanisms of the brain that are the Hebbian and non-Hebbian learning
      rules can be understood as processes devoted to generate the appropriate
      clustering of both synchronized and chaotic ensembles. The measurements obtained
      from the hardware implementation of different types of neural systems suggest
      that the brain processing can be governed by the superposition of these two
      complementary states with complementary functionalities (nonlinear processing for
      synchronized states and information convolution and parallelization for chaotic).

PMID- 24875786
TI  - Optimal sparse approximation with integrate and fire neurons.
AB  - Sparse approximation is a hypothesized coding strategy where a population of
      sensory neurons (e.g. V1) encodes a stimulus using as few active neurons as
      possible. We present the Spiking LCA (locally competitive algorithm), a rate
      encoded Spiking Neural Network (SNN) of integrate and fire neurons that calculate
      sparse approximations. The Spiking LCA is designed to be equivalent to the
      nonspiking LCA, an analog dynamical system that converges on a l(1)-norm sparse
      approximations exponentially. We show that the firing rate of the Spiking LCA
      converges on the same solution as the analog LCA, with an error inversely
      proportional to the sampling time. We simulate in NEURON a network of 128 neuron
      pairs that encode 8 * 8 pixel image patches, demonstrating that the network
      converges to nearly optimal encodings within 20 ms of biological time. We also
      show that when using more biophysically realistic parameters in the neurons, the
      gain function encourages additional l(0)-norm sparsity in the encoding, relative
      both to ideal neurons and digital solvers. 

PMID- 24875787
TI  - Simulating vertical and horizontal inhibition with short-term dynamics in a multi
      column multi-layer model of neocortex.
AB  - The paper introduces a multi-layer multi-column model of the cortex that uses
      four different neuron types and short-term plasticity dynamics. It was designed
      with details of neuronal connectivity available in the literature and meets these
      conditions: (1) biologically accurate laminar and columnar flows of activity, (2)
      normal function of low-threshold spiking and fast spiking neurons, and (3)
      ability to generate different stages of epileptiform activity. With these
      characteristics the model allows for modeling lesioned or malformed cortex, i.e.
      examine properties of developmentally malformed cortex in which the balance
      between inhibitory neuron subtypes is disturbed. 

PMID- 24875788
TI  - A generalized Leaky Integrate-and-Fire neuron model with fast implementation
      method.
AB  - This study introduces a new Generalized Leaky Integrate-and-Fire (GLIF) neuron
      model with variable leaking resistor and bias current in order to reproduce
      accurately the membrane voltage dynamics of a biological neuron. The accuracy of
      this model is ensured by adjusting its parameters to the statistical properties
      of the Hodgkin-Huxley model outputs; while the speed is enhanced by introducing a
      Generalized Exponential Moving Average method that converts the parameterized
      kernel functions into pre-calculated lookup tables based on an analytic solution
      of the dynamic equations of the GLIF model. 

PMID- 24875789
TI  - An optimization spiking neural p system for approximately solving combinatorial
      optimization problems.
AB  - Membrane systems (also called P systems) refer to the computing models abstracted
      from the structure and the functioning of the living cell as well as from the
      cooperation of cells in tissues, organs, and other populations of cells. Spiking
      neural P systems (SNPS) are a class of distributed and parallel computing models
      that incorporate the idea of spiking neurons into P systems. To attain the
      solution of optimization problems, P systems are used to properly organize
      evolutionary operators of heuristic approaches, which are named as membrane
      inspired evolutionary algorithms (MIEAs). This paper proposes a novel way to
      design a P system for directly obtaining the approximate solutions of
      combinatorial optimization problems without the aid of evolutionary operators
      like in the case of MIEAs. To this aim, an extended spiking neural P system
      (ESNPS) has been proposed by introducing the probabilistic selection of evolution
      rules and multi-neurons output and a family of ESNPS, called optimization spiking
      neural P system (OSNPS), are further designed through introducing a guider to
      adaptively adjust rule probabilities to approximately solve combinatorial
      optimization problems. Extensive experiments on knapsack problems have been
      reported to experimentally prove the viability and effectiveness of the proposed
      neural system. 

PMID- 24875790
TI  - Code-specific learning rules improve action selection by populations of spiking
      neurons.
AB  - Population coding is widely regarded as a key mechanism for achieving reliable
      behavioral decisions. We previously introduced reinforcement learning for
      population-based decision making by spiking neurons. Here we generalize
      population reinforcement learning to spike-based plasticity rules that take
      account of the postsynaptic neural code. We consider spike/no-spike, spike count
      and spike latency codes. The multi-valued and continuous-valued features in the
      postsynaptic code allow for a generalization of binary decision making to multi
      valued decision making and continuous-valued action selection. We show that code
      specific learning rules speed up learning both for the discrete classification
      and the continuous regression tasks. The suggested learning rules also speed up
      with increasing population size as opposed to standard reinforcement learning
      rules. Continuous action selection is further shown to explain realistic learning
      speeds in the Morris water maze. Finally, we introduce the concept of action
      perturbation as opposed to the classical weight- or node-perturbation as an
      exploration mechanism underlying reinforcement learning. Exploration in the
      action space greatly increases the speed of learning as compared to exploration
      in the neuron or weight space. 

PMID- 24875793
TI  - Recessive mutation identifies auxin-repressed protein ARP1, which regulates
      growth and disease resistance in tobacco.
AB  - To study the molecular mechanism that underpins crosstalk between plant growth
      and disease resistance, we performed a mutant screening on tobacco and created a
      recessive mutation that caused the phenotype of growth enhancement and resistance
      impairment (geri1). In the geri1 mutant, growth enhancement accompanies promoted
      expression of growth-promoting genes, whereas repressed expression of defense
      response genes is consistent with impaired resistance to diseases caused by
      viral, bacterial, and oomycete pathogens. The geri1 allele identifies a single
      genetic locus hypothetically containing the tagged GERI1 gene. The isolated GERI1
      gene was predicted to encode auxin-repressed protein ARP1, which was determined
      to be 13.5 kDa in size. The ARP1/GERI1 gene was further characterized as a
      repressor of plant growth and an activator of disease resistance based on genetic
      complementation, gene silencing, and overexpression analyses. ARP1/GERI1
      resembles pathogen-associated molecular patterns and is required for them to
      repress plant growth and activate plant immunity responses. ARP1/GERI1 represses
      growth by inhibiting the expression of AUXIN RESPONSE FACTOR gene ARF8, and
      ARP1/GERI1 recruits the NPR1 gene, which is essential for the salicylic-acid
      mediated defense, to coregulate disease resistance. In conclusion, ARP1/GERI1 is
      an integral regulator for crosstalk between growth and disease resistance in the
      plant. 

PMID- 24875792
TI  - Provider and patient expectations for dietary supplement discussions.
AB  - BACKGROUND: Dietary supplement use in the United States is common. Patients can
      procure supplements without a prescription, and often do not disclose supplement
      use to their healthcare providers. Providers and patients may be uncertain about
      what would be appropriate or helpful in discussions of supplements during routine
      office visits. OBJECTIVE: To explore provider and patient expectations for
      discussions of dietary supplements. DESIGN: Semi-structured interviews were
      conducted with a purposeful sample of healthcare providers from three specialties
      and their patients who reported taking supplements. PARTICIPANTS: Thirty-five
      outpatient providers (14 primary care, six integrative medicine, and 15
      complementary and alternative medicine (CAM) providers) and 107 of their
      patients. APPROACH: Qualitative analysis of transcripts using grounded theory and
      iterative review. RESULTS: Both providers and patients raised twelve common
      topics about dietary supplements that they felt were important to discuss during
      office visits, such as: supplements taken; supplement risks (interactions,
      safety/harm, side effects/adverse events); treatment benefits; efficacy;
      alternative treatments; and patient expectations/preferences for treatment. Some
      topics were mentioned more frequently by providers than patients, such as how to
      take, reason for taking, and evidence for use. Providers raised several topics
      that were mentioned infrequently by patients. Supplement costs and regulations
      were not brought up by any patients, even though consideration of these topics
      could influence patient decisions to take supplements. Complementary healthcare
      providers brought up topics not mentioned by primary care providers, such as the
      importance of supplement brands and supplement mega-dosing. CONCLUSIONS: Patients
      and providers have concordant views about the need to discuss patient supplement
      use and ensure patient safety. Patients may undervalue, be unaware of, or
      discount information about cost or regulations that could affect their decision
      making about supplement use. Future studies could examine the value,
      acceptability, and influence of a more comprehensive approach to discussions to
      help patients appropriately evaluate supplements.

PMID- 24875794
TI  - Secret lifestyles of Neurospora crassa.
AB  - Neurospora crassa has a long history as an excellent model for genetic, cellular,
      and biochemical research. Although this fungus is known as a saprotroph, it
      normally appears on burned vegetations or trees after forest fires. However, due
      to a lack of experimental evidence, the nature of its association with living
      plants remains enigmatic. Here we report that Scots pine (Pinus sylvestris) is a
      host plant for N. crassa. The endophytic lifestyle of N. crassa was found in its
      interaction with Scots pine. Moreover, the fungus can switch to a pathogenic
      state when its balanced interaction with the host is disrupted. Our data reveal
      previously unknown lifestyles of N. crassa, which are likely controlled by both
      environmental and host factors. Switching among the endophytic, pathogenic, and
      saprotrophic lifestyles confers upon fungi phenotypic plasticity in adapting to
      changing environments and drives the evolution of fungi and associated plants. 

PMID- 24875796
TI  - Ameliorating reperfusion injury in STEMI: dead or alive?

PMID- 24875795
TI  - Right heart dysfunction in heart failure with preserved ejection fraction.
AB  - AIM: Right heart function is not well characterized in patients with heart
      failure and preserved ejection fraction (HFpEF). The goal of this study was to
      examine the haemodynamic, clinical, and prognostic correlates of right
      ventricular dysfunction (RVD) in HFpEF. METHODS AND RESULTS: Heart failure and
      preserved ejection fraction patients (n = 96) and controls (n = 46) underwent
      right heart catheterization, echocardiographic assessment, and follow-up. Right
      and left heart filling pressures, pulmonary artery (PA) pressures, and right
      sided chamber dimensions were higher in HFpEF compared with controls, while left
      ventricular size and EF were similar. Right ventricular dysfunction (defined by
      RV fractional area change, FAC <35%) was present in 33% of HFpEF patients and was
      associated with more severe symptoms and greater comorbidity burden. Right
      ventricular function was impaired in HFpEF compared with controls using both load
      dependent (FAC: 40 +/- 10 vs. 53 +/- 7%, P < 0.0001) and load-independent indices
      (FAC adjusted to PA pressure, P = 0.003), with enhanced afterload-sensitivity
      compared with controls (steeper FAC vs. PA pressure relationship). In addition to
      haemodynamic load, RVD in HFpEF was associated with male sex, atrial
      fibrillation, coronary disease, and greater ventricular interdependence. Over a
      median follow-up of 529 days (IQR: 143-1066), 31% of HFpEF patients died. In Cox
      analysis, RVD was the strongest predictor of death (HR: 2.4, 95% CI: 1.6-2.6; P <
      0.0001). CONCLUSION: Right heart dysfunction is common in HFpEF and is caused by
      both RV contractile impairment and afterload mismatch from pulmonary
      hypertension. Right ventricular dysfunction in HFpEF develops with increasing PA
      pressures, atrial fibrillation, male sex, and left ventricular dysfunction, and
      may represent a novel therapeutic target.

PMID- 24875797
TI  - Should we use the angiotensin-converting enzyme inhibitors for the treatment of
      anti-VEGF-induced hypertension?

PMID- 24875799
TI  - Adverse events with everolimus in BOLERO-2.

PMID- 24875798
TI  - Controversies and role of HPV16 in recurrent/metastatic squamous cell cancers of
      the head and neck.

PMID- 24875801
TI  - Inferring sources for mercury to inland lakes using sediment chronologies of
      polycyclic aromatic hydrocarbons.
AB  - Sediment chronologies from inland lakes suggest the influence of local to sub
      regional scale sources for mercury (Hg). However, apportionment of sources for Hg
      using sediment chronologies is difficult due to the mixing of sources and
      pathways. Mercury and polycyclic aromatic hydrocarbons (PAH) often share common
      sources and pathways into the environment. Thus, chronologies of PAHs in dated
      cores of sediments might be a useful tool to infer sources of Hg. Sediment cores
      from seven inland lakes of Michigan were collected for measurement of PAHs and Hg
      and dated by use of (210)Pb. PAH concentrations and ratios of kinetic and
      thermodynamic PAH compounds were used to infer sources of Hg. Ratios indicate the
      existence of modern combustion sources to each lake and historic combustion
      sources to lakes near cement kilns and an iron foundry. Coal combustion sources
      were identified for two lakes near urban centers. Whereas a petroleum combustion
      source was identified for a lake that has a coal fired power plant along its
      shoreline. These results have implications for the cycling of Hg on local to
      regional scales. 

PMID- 24875800
TI  - Endogenous antibodies for tumor detection.
AB  - The study of cancer immunology has provided diagnostic and therapeutic
      instruments through serum autoantibody biomarkers and exogenous monoclonal
      antibodies. While some endogenous antibodies are found within or surrounding
      transformed tissue, the extent to which this exists has not been entirely
      characterized. We find that in transgenic and xenograft mouse models of cancer,
      endogenous gamma immunoglobulin (IgG) is present at higher concentration in
      malignantly transformed organs compared to non-transformed organs in the same
      mouse or organs of cognate wild-type mice. The enrichment of endogenous
      antibodies within the malignant tissue provides a potential means of identifying
      and tracking malignant cells in vivo as they mutate and diversify. Exploiting
      these antibodies for diagnostic and therapeutic purposes is possible through the
      use of agents that bind endogenous antibodies. 

PMID- 24875802
TI  - Soil and soil environmental quality monitoring in China: a review.
AB  - Over the past few decades, numerous concerns have been raised in China over the
      issue of environmental sustainability. Various soil survey and monitoring
      programs have been carried out in China to study soil quality, and to provide a
      scientific basis for environment policy making. This paper provides an overview
      of past and current soil quality surveys and monitoring activities in China. This
      paper includes a summary of concerns over background concentrations of elements
      in soil, and soil environmental standards and guidelines in China. Levels of
      pollution in urban soil, agricultural soil, and soil in mining and smelting areas
      were compared using the concentrations and pollution indexes. In addition to soil
      surveys, soil monitoring is essential to study the data and to examine the
      effects of contaminants in soils. However, the current soil quality monitoring
      system was insufficient to accurately determine the soil quality status of soils
      across China. For accurate soil monitoring in China, it will be necessary to set
      up routine monitoring systems at various scales (national, provincial, and local
      scales), taking into consideration monitoring indicators and quality assurance.
      This is currently an important priority for the environmental protection
      administration of China. 

PMID- 24875803
TI  - Child exposure to indoor and outdoor air pollutants in schools in Barcelona,
      Spain.
AB  - Proximity to road traffic involves higher health risks because of atmospheric
      pollutants. In addition to outdoor air, indoor air quality contributes to overall
      exposure. In the framework of the BREATHE study, indoor and outdoor air pollution
      was assessed in 39 schools in Barcelona. The study quantifies indoor and outdoor
      air quality during school hours of the BREATHE schools. High levels of fine
      particles (PM2.5), nitrogen dioxide (NO2), equivalent black carbon (EBC),
      ultrafine particle (UFP) number concentration and road traffic related trace
      metals were detected in school playgrounds and indoor environments. PM2.5 almost
      doubled (factor of 1.7) the usual urban background (UB) levels reported for
      Barcelona owing to high school-sourced PM2.5 contributions: [1] an indoor
      generated source characterised mainly by organic carbon (OC) from organic textile
      fibres, cooking and other organic emissions, and by calcium and strontium (chalk
      dust) and; [2] mineral elements from sand-filled playgrounds, detected both
      indoors and outdoors. The levels of mineral elements are unusually high in PM2.5
      because of the breakdown of mineral particles during playground activities.
      Moreover, anthropogenic PM components (such as OC and arsenic) are dry/wet
      deposited in this mineral matter. Therefore, PM2.5 cannot be considered a good
      tracer of traffic emissions in schools despite being influenced by them. On the
      other hand, outdoor NO2, EBC, UFP, and antimony appear to be good indicators of
      traffic emissions. The concentrations of NO2 are 1.2 times higher at schools than
      UB, suggesting the proximity of some schools to road traffic. Indoor levels of
      these traffic-sourced pollutants are very similar to those detected outdoors,
      indicating easy penetration of atmospheric pollutants. Spatial variation shows
      higher levels of EBC, NO2, UFP and, partially, PM2.5 in schools in the centre
      than in the outskirts of Barcelona, highlighting the influence of traffic
      emissions. Mean child exposure to pollutants in schools in Barcelona attains
      intermediate levels between UB and traffic stations. 

PMID- 24875804
TI  - Short daily versus conventional hemodialysis for hypertensive patients: a
      randomized cross-over study.
AB  - BACKGROUND: Treatment of end stage renal disease patients with short daily
      hemodialysis has been associated with an improvement in blood pressure. It is
      unclear from these studies if anti-hypertensive management had been optimized
      prior to starting short daily hemodialysis. Also, the potential mechanism(s) of
      blood pressure improvement remain to be fully elucidated. STUDY DESIGN, SETTING
      AND PARTICIPANTS: We undertook a randomized cross-over trial in adult
      hypertensive patients with ESRD treated with conventional hemodialysis to
      determine: 1) if short-daily hemodialysis is associated with a reduction in
      systolic blood pressure after a 3-month blood pressure optimization period and;
      2) the potential mechanism(s) of blood pressure reduction. Blood pressure was
      measured using Canadian Hypertension Education Program guidelines. Extracellular
      fluid volume (ECFV) was assessed with bioimpedance. Serum catecholamines were
      used to assess the sympathetic nervous system. Interleukin-6 (IL-6) and
      thiobarbituric acid reactive substances (T-BARS) were used as markers of
      inflammation and oxidative stress respectively. RESULTS: After a 3-month run-in
      phase in which systolic blood pressure improved, there was no significant
      difference in pre-dialysis systolic pressure between short-daily and conventional
      hemodialysis (p = 0.39). However, similar blood pressures were achieved on fewer
      anti-hypertensive medications with short daily hemodialysis compared to
      conventional hemodialysis (p = 0.01). Short daily hemodialysis, compared to
      conventional hemodialysis, was not associated with a difference in dry weight or
      ECFV (p = 0.77). Sympathetic nervous system activity as assessed by plasma
      epinephrine (p = 1.0) and norepinephrine (p = 0.52) was also not different.
      Markers of inflammation (p = 0.42) and oxidative stress (p = 0.83) were also
      similar between the two treatment arms. CONCLUSIONS: Patients treated with short
      daily, compared to conventional hemodialysis, have similar blood pressure control
      on fewer anti-hypertensive medications. The mechanism(s) by which short daily
      hemodialysis allows for decreased anti-hypertensive medication use remains
      unclear but effects on sodium balance and changes in peripheral vascular
      resistance require further study. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT00759967.

PMID- 24875806
TI  - Pyrexia of postimplantation syndrome for patients undergoing (thoracic)
      endovascular aortic repair.
AB  - OBJECTIVE: While a clear definition and explanation to postimplantation syndrome
      are yet to be clarified, this study aims to investigate its nature by
      retrospectively analyzing postprocedural fever pattern with patient
      characteristics, procedure details, and responses to medical treatments.
      MATERIALS AND METHOD: Twenty-three patients undergoing (thoracic) endovascular
      aortic repair between January 2011 and January 2012 were studied for their
      postimplantation fever pattern. The demographic information, procedure
      specifications, and postprocedure care details were collected for statistical
      analysis to find associations between fever pattern and the above-mentioned
      parameters. RESULTS: None of the postprocedure microbial studies returned
      positive. Longer fever duration and higher fever frequency are statistically
      associated with younger age (95% confidence interval [CI] -0.82 to -0.04, p <
      0.04 and 95% CI -0.74 to -0.01, p = 0.05 respectively), longer procedure duration
      (95% CI 0.35-0.90, p < 0.01 and 95% CI 0.02-0.75, p = 0.04 respectively), more
      entry sites created (95% CI 0.09-0.95 p < 0.03 and 95% CI 0.02-0.88, p < 0.04,
      respectively), and longer stent grafts implanted (95% CI 0.27-0.89, p < 0.01,
      fever duration only). Fever pattern and different postprocedure medical treatment
      did not convey a statistically significant association, but effective and
      dramatic response to steroids was observed in patients with persistent pyrexia
      that responded poorly to antibiotics and nonsteroidal anti-inflammatory drugs.
      CONCLUSION: Our findings support the view that postimplantation syndrome is
      caused by host immune response; none of our cases are related with infection and
      no benefits were observed from the prolonged use of antibiotics, thus adding to
      the plausibility of employing steroids as part of the postprocedure care scheme.

PMID- 24875805
TI  - Notchless is required for axial skeleton formation in mice.
AB  - Maintenance of cell survival is essential for proper embryonic development. In
      the mouse, Notchless homolog 1 (Drosophila) (Nle1) is instrumental for survival
      of cells of the inner cell mass upon implantation. Here, we analyze the function
      of Nle1 after implantation using the Meox2(tm1(cre)Sor) mouse that expresses the
      Cre recombinase specifically in the epiblast at E5.5. First, we find that NLE1
      function is required in epiblast cells, as Nle1-deficient cells are rapidly
      eliminated. In this report, we also show that the Meox2(Cre) transgene is active
      in specific tissues during organogenesis. In particular, we detect high Cre
      expression in the vertebral column, ribs, limbs and tailbud. We took advantage of
      this dynamic expression profile to analyze the effects of inducing mosaic
      deletion of Nle1 in the embryo. We show that Nle1 deletion in this context,
      results in severe developmental anomalies leading to lethality at birth. Mutant
      embryos display multiple developmental defects in particular during axial
      skeletal formation. We also provide evidence that axial defects are due to an
      increase in apoptotic cell death in the somite at E9.5. These data demonstrate an
      essential role for Nle1 during organogenesis and in particular during axial
      development.

PMID- 24875807
TI  - Increased content of resistin in epicardial adipose tissue of patients with
      advanced coronary atherosclerosis and history of myocardial infarction.
AB  - OBJECTIVES: The aim of the study was to assess whether the plasma level and
      content of adipokines, in adipose tissue, is associated with a medical history of
      myocardial infarction. PATIENTS AND METHODS: The study group consisted of 33
      consecutive patients (12 females, 21 males, aged 68.6 +/- 6.8 years) who
      underwent cardiac bypass surgery. Patients were divided into groups; group 1
      presented with a history of myocardial infarction and group 2 presented without a
      history of myocardial infarction. During cardiac surgery, samples of epicardial
      adipose tissue, adipose tissue located at internal mammary artery, subcutaneous
      adipose tissue, and blood samples were taken for further assessment.Significantly
      higher levels of resistin in adipose tissue from the epicardial tissue were found
      in group 1 than in group 2: median and interquartile range, respectively, 37.2
      (8.9-121.5) ng/g versus 15.0 (7.1-24.1) ng/g; p < 0.049. Multivariate analysis
      found that previous myocardial infarction was associated with male gender, older
      age, and higher content of resistin in epicardial adipose tissue. CONCLUSION: The
      resistin content in epicardial adipose tissue in patients with advanced coronary
      atherosclerosis seems higher in those with a history myocardial infarction.
      Increased resistin epicardial content seems related to the previous myocardial
      infarction independent of the other established risk factors such as age and male
      gender. The importance of paracrine function of adipose pericardial tissue in the
      occurrence of complications of atherosclerosis merits further investigations.

PMID- 24875809
TI  - Major bleeding in patients with mediastinitis: a heartbreaking series.
AB  - Deep sternal wound infection (DSWI) is a life-threatening complication that
      develops in 5% of patients undergoing median sternotomy. One feared complication
      is major bleeding, associated with up to 50% mortality. We characterized a series
      of patients who experienced major bleeding following DSWI. We included eight
      patients with DSWI who experienced major bleeding at our institution from 1990 to
      2012. The median age was 70.9 (range, 47-81) and the cohort consisted of seven
      male patients and one female patient. All eight patients required emergent
      surgical repair for the bleeding and all survived past 30 days postoperatively
      from the repair. 

PMID- 24875808
TI  - Outcomes of outpatient treatment for primary spontaneous pneumothorax using a
      small-bore portable thoracic drainage device.
AB  - BACKGROUND: There is no consensus regarding the initial intervention for primary
      spontaneous pneumothorax. We report the outcomes of outpatient treatment for
      primary spontaneous pneumothorax using a portable thoracic drainage device.
      PATIENTS AND METHODS: Between April 2007 and December 2011, 99 consecutive
      patients with a first episode of primary spontaneous pneumothorax were indicated
      for insertion of a portable thoracic drainage device. All patients were treated
      with a small-bore portable thoracic drainage device that consists of a flexible
      9F silicone catheter with one-way valves and a small plastic chamber. Successful
      treatment was defined as when the pneumothorax was resolved after the insertion
      of a portable thoracic drainage device solely on an outpatient basis. Demographic
      data and treatment outcomes were obtained by a retrospective chart review.
      RESULTS: Ninety-seven patients (98%) with a first primary spontaneous
      pneumothorax were discharged from the emergency department after insertion of a
      portable thoracic drainage device. Ninety-three patients (94%) resolved with
      outpatient treatment. The median duration of portable thoracic drainage device
      insertion was 4 days (range, 0-33 days). The recurrence rate after treatment with
      a portable thoracic drainage device was 34% (32/93). There were two infections
      (2.0%), two instances of hemothoraces (2.0%), and one severe discomfort at the
      insertion site (1.0%). There were no cases of tension pneumothorax or reexpansion
      edema. CONCLUSION: Outpatient treatment for primary spontaneous pneumothorax
      using a portable thoracic drainage device had a high success rate with few
      serious complications and an acceptable recurrence rate.

PMID- 24875810
TI  - Prospective randomized trial comparing buttressed versus nonbuttressed stapling
      in patients undergoing pulmonary lobectomy.
AB  - BACKGROUND: The aim of this study was to evaluate the efficacy of buttressed
      stapling using a stapler with an attached polyglycolic acid sheet in reducing the
      rate of air leak associated with pulmonary lobectomy. Materials and METHODS: A
      prospective, randomized, phase III study was conducted to confirm the superiority
      of a buttressed stapler in a test treatment group to a conventional nonbuttressed
      stapler in a current international standard of care group among patients
      undergoing pulmonary lobectomy. The primary end point was the frequency of
      intraoperative air leaks. RESULTS: Although no fatal postoperative bleeding
      occurred in the present study, this trial closed early with 100 patients because
      the manufacturer recalled the buttressed stapler based on reports of 13 serious
      injuries and 3 fatalities following pulmonary resection in routine clinical
      practice. A total of 76 patients treated with a stapler (35 in the non-B group
      and 41 in the B group) were included as subjects in the analysis. No statistical
      differences were observed between the groups in the frequency of intraoperative
      air leaks (22 [63%] vs. 26 [63%]) or the postoperative duration of air leaks
      (mean: 3.5 vs. 2.9 days). The frequency of air leak from stapler holes was
      significantly lower in the B group than in the non-B group (2% [1/41] vs. 20%
      [7/35]; p=0.016). CONCLUSIONS: The efficacy of buttressed stapling in reducing
      the rate of air leak in patients undergoing pulmonary lobectomy could not be
      clearly demonstrated. However, air leak from stapler holes can be prevented with
      buttressed stapling.

PMID- 24875811
TI  - GUCY2D- or GUCA1A-related autosomal dominant cone-rod dystrophy: is there a
      phenotypic difference?
AB  - PURPOSE: To compare the phenotype of patients with heterozygous mutation in
      GUCY2D or GUCA1A causing autosomal dominant cone or cone-rod dystrophies.
      METHODS: Five patients from one family with GUCA1A and nine patients from four
      families with GUCY2D mutations were included. Psychophysical and
      electrophysiological examinations were performed to study retinal function.
      Fundus autofluorescence imaging and spectral domain optical coherence tomography
      were performed for morphologic characterization. RESULTS: Genetic analysis
      revealed the mutation c.451C>T (p.L151F) in the GUCA1A family. In the GUCY2D
      group, c.2512C>T (p.R838C) was the most frequent (2 families), c.2512C>G
      (p.R838G) and c.2513G>A (p.R838H) were found in one family each. Visual acuity
      was reduced to 0.04 to 0.7 in GUCA1A and to 0.014 to 0.5 in patients with GUCY2D.
      Dark adaptation showed elevated thresholds in the GUCY2D group. Scotopic
      electroretinography revealed a tendency to a more affected rod function in the
      GUCY2D group. Photopic electroretinography showed residual or absent responses in
      both groups. Fundus alterations were confined to the macula in both groups.
      CONCLUSION: GUCA1A and GUCY2D mutations are both accompanied by similar pattern
      of generalized cone dysfunction with a tendency to less involvement of the rod
      photoreceptors and a less severe phenotype in patients with GUCA1A.

PMID- 24875813
TI  - Editorial.

PMID- 24875814
TI  - Commentary on Kawanishi et al. 'A comparison of 3-D computed tomography versus 2
      D radiography measurements of ulnar variance and ulno-lunate distance during
      forearm rotation'.

PMID- 24875815
TI  - Advice on academic research in hand surgery.

PMID- 24875816
TI  - Re: Dieter Buck-Gramcko.

PMID- 24875817
TI  - [Acute multifocal posterior placoid pigment epitheliopathy and central retinal
      vein occlusion: association in a sarcoidosis patient].
AB  - Acute multifocal posterior placoid pigment epitheliopathy is a chorioretinal
      inflammatory disease characterized by whitish lesions with ill-defined margins,
      deep to the retina and concentrated in the posterior pole. We report the case of
      a 17-year-old man who presented with the typical findings of bilateral acute
      multifocal posterior placoid pigment epitheliopathy. He developed secondary
      central retinal vein occlusion in the right eye. Systemic manifestations and
      additional investigations resulted in a diagnosis of sarcoidosis.

PMID- 24875818
TI  - Exploring the role of anti-angiogenic therapies in prostate cancer: results from
      the phase 3 trial of sunitinib.

PMID- 24875819
TI  - Intensity of stromal changes is associated with tumor relapse in clinically
      advanced prostate cancer after castration therapy.
AB  - Reactive stromal changes in prostate cancer (PCa) are likely involved in the
      emergence of castration-resistant PCa (CRPC). This study was designed to
      investigate stromal changes in patients with clinically advanced PCa and analyze
      their prognostic significance. Prostate needle biopsies obtained from 148
      patients before castration therapy were analyzed by Masson trichrome staining and
      immunohistochemical analysis of vimentin and desmin. Reactive stroma grading was
      inversely correlated with Gleason score. Stroma grade (Masson stain 82.8% vs
      45.6%, P < 0.001) and vimentin expression (P = 0.005) were significantly higher,
      and desmin expression (P = 0.004) significantly lower, in reactive stroma of
      tumors with a Gleason score of 6-7 than in adjacent peritumoral tissue. Kaplan
      Meier analysis showed a significant association between reactive stroma grade in
      tumors and the occurrence of CRPC in patients with a Gleason score of 6-7 (P =
      0.009). Furthermore, patients with higher vimentin or lower desmin expression had
      a shorter disease-free period. In multivariate analysis, only vimentin expression
      was a significant predictor of tumor relapse (hazard ratio 1.78, 95% confidence
      interval 1.12-10.26, P = 0.012). These findings indicate that the intensity of
      reactive stroma is associated with castration responsiveness, especially in
      patients with a lower Gleason score where the abundant stroma component is most
      frequently found. High expression of vimentin in tumor stroma was independently
      associated with poor outcomes in patients with Gleason scores of 6-7, and may
      serve as a new prognostic marker in daily practice.

PMID- 24875821
TI  - Prostatic stromal tumor of uncertain malignant potential presenting as a huge
      bladder mass: an unusual case.

PMID- 24875820
TI  - Association of 370-371insACA, 494T>C, and 1423C>T haplotype in ubiquitin-specific
      protease 26 gene and male infertility: a meta-analysis.
AB  - Whether the 370-371insACA, 494T>C, and 1423C>T haplotype in ubiquitin-specific
      protease 26 (USP26) gene is associated with male infertility is controversial. To
      clarify this issue, we conducted a meta-analysis based on the most recent
      studies. Eligible studies were screened by using PubMed and Embase. Pooled odd
      ratio (OR) with 95% confidence interval (CI) was calculated with fixed effect
      models. Ten studies with 1603 patients and 2505 controls were included. Overall,
      the results indicated that there was an association between the haplotype and
      male infertile risk (OR = 1.74, 95% CI: 1.09-2.77). The OR calculated based on
      the five studies in Asia and three in Europe was 1.96 (95% CI: 1.05-3.67) and
      1.54 (95% CI: 0.75-3.16) respectively, however, the OR was 0.86 (95% CI: 0.05
      15.29) based on the two investigations in America. In addition, the data from the
      patients with azoospermia (AZO) showed an increased pooled OR of 2.35 (95% CI:
      1.22-4.50). In contrast, the studies with oligoasthenoteratozoospermia (OAT)
      exhibited that the pooled OR was 0.97 (95% CI: 0.43-2.16). Our analyses indicate
      that there is an association of alteration in USP26 with male infertility,
      especially in AZO and Asian population.

PMID- 24875822
TI  - Management of localized prostate cancer: the pendulum swings (back to the
      middle).

PMID- 24875824
TI  - Redundant prepuce increases the odds of chronic prostatitis/chronic pelvic pain
      syndrome (CP/CPPS).
AB  - Some published evidence has revealed that the dendritic cells can interact with
      pathogens that exist in the inner foreskin. This information provides a new
      vision that pathogens could play a role through the redundant prepuce; numerous
      studies have failed to find pathogens in prostates of patients who had chronic
      prostatitis/chronic pelvic pain syndrome (CP/CPPS). However, no studies have
      reported an association between foreskin length and CP/CPPS. Hence, we conducted
      a retrospective case-control study of clinical data from 322 CP/CPPS patients
      (case group) and 341 nonCP/CPPS patients (control group). Demographic
      characteristics, lifestyle factors, and foreskin lengths were collected and
      analyzed. Multivariate logistic regression was adopted to calculate the odds of
      foreskin length for CP/CPPS. According to the multivariate logistic regression
      results, when the foreskin length covered up more than half of the glans penis,
      the odds for CP/CPPS were higher with an increased foreskin (odds ratio (OR):
      1.66, 95% confidence interval (CI): 1.04-2.66). In comparison, when the glans
      penis was completely covered by the foreskin, the OR value increased to 1.86 (95%
      CI, 1.2-2.88). The study results showed an association between foreskin length
      and the odds of CP/CPPS. When the foreskin length covered up more than half of
      the glans penis, there were greater odds for CP/CPPS. This possible mechanism
      might result from interaction between pathogens and DCs in the inner foreskin,
      consequently activating T-cells to mediate allergic inflammation in the prostate
      and producing the autoimmunizations causing CP/CPPS. 

PMID- 24875823
TI  - Risk factors for hypospadias in China.
AB  - This case-controlled study was designed to evaluate the association between
      various baseline parental factors and the risk of hypospadias in China. Patients
      were selected from tertiary referral hospitals in Anhui, a province in mid
      eastern China. A questionnaire was given to the parents of each patient. The
      final database included 193 cases and 835 controls. The incidence of additional
      coexistent anomalies was 13.0%, primarily cryptorchidism (9.8%). Ten patients
      (5.1%) were from families with genital anomaly, including five families (2.6%)
      with hypospadias. The risks of hypospadias was higher for children of mothers >
      35 (odds ratio [OR] =1.47) and < 18 (OR = 2.95) years of age, and in mothers who
      had consumed alcohol (OR = 2.67), used drugs (OR = 1.53) and had an infection (OR
      = 1.87) during pregnancy. The risk of hypospadias was also higher when mothers
      (OR = 1.68) and fathers (OR = 1.74) were engaged in agriculture. Other factors
      assessed were not associated with the risk of hypospadias.

PMID- 24875825
TI  - Antiglycation activity of quinoline derivatives- a new therapeutic class for the
      management of type 2 diabetes complications.
AB  - We report here a new class of compounds, quinoline derivatives, as potential
      inhibitors of in vitro bovine serum albumin-methylglyoxal glycation. Among
      compounds 1-19, compound 14 was found to be the most active analog with IC50 of
      282.98 +/- 8.4 uM. Compounds 12 (IC50 = 661.78 +/- 8.7 uM) and 15 (IC50 = 629.43
      +/- 7.85 7 uM) were also identified as modest inhibitors, in comparison to the
      standard inhibitor, rutin (IC50 = 294.50 +/- 1.5 uM). When evaluated for
      antioxidant activity through in vitro DPPH radical scavenging assay, compounds 3
      (IC50 = 2.19 +/- 0.27 uM), 6 (IC50 = 7.35 +/- 2.27 uM), 11 (IC50 = 8.96 +/- 0.56
      uM), and 12 (IC50 = 10.11 +/- 2.03 uM), and 15 (IC50 = 7.01 +/- 3.87 uM) were
      found to be more active than the standard i.e. gallic acid (IC50 = 23.34 +/- 0.43
      uM). These compounds were also evaluated for cytotoxicity against rat fibroblast
      cell line (3T3 cell line). All compounds were found to be non-toxic in cellular
      model. This study identifies quinoline derivatives as a new class of inhibitors
      of protein glycation in vitro, along with antioxidant and non-toxic nature. These
      properties make them interesting leads for further studies as potential anti
      diabetic agents.

PMID- 24875826
TI  - Quinoxaline derivatives: novel and selective butyrylcholinesterase inhibitors.
AB  - Alzheimer's disease (AD) is a progressive brain disorder which occurs due to
      lower levels of acetylcholine (ACh) neurotransmitters, and results in a gradual
      decline in memory and other cognitive processes. Acetycholinesterase (AChE) and
      butyrylcholinesterase (BChE) are considered to be primary regulators of the ACh
      levels in the brain. Evidence shows that AChE activity decreases in AD, while
      activity of BChE does not change or even elevate in advanced AD, which suggests a
      key involvement of BChE in ACh hydrolysis during AD symptoms. Therefore,
      inhibiting the activity of BChE may be an effective way to control AD associated
      disorders. In this regard, a series of quinoxaline derivatives 1-17 was
      synthesized and biologically evaluated against cholinesterases (AChE and BChE)
      and as well as against alpha- chymotrypsin and urease. The compounds 1-17 were
      found to be selective inhibitors for BChE, as no activity was found against other
      enzymes. Among the series, compounds 6 (IC50 = 7.7 +/- 1.0 uM) and 7 (IC50 = 9.7
      +/- 0.9 uM) were found to be the most active inhibitors against BChE. Their IC50
      values are comparable to the standard, galantamine (IC50 = 6.6 +/- 0.38 uM).
      Their considerable BChE inhibitory activity makes them selective candidates for
      the development of BChE inhibitors. Structure-activity relationship (SAR) of this
      new class of selective BChE inhibitors has been discussed. 

PMID- 24875827
TI  - Utilizing an earthworm bioassay (Eisenia andrei) to assess a South African soil
      screening value with regards to effects from a copper manufacturing industry.
AB  - Metal contamination of soil due to industrialization has become an increasingly
      important problem in South Africa. This study aimed to investigate the potential
      impact of a copper (CuSO4.5H2O) production company on the soil environment.
      Bioassays using Eisenia andrei were performed to assess changes in biomass,
      reproduction and a biomarker, neutral red retention time, over a 28 day period.
      Earthworms exposed to soils from the Cu production site differed significantly (p
      < 0.05) from those exposed to soils 500 m and 5 km away in terms of the measured
      endpoints. These findings are consistent with the results from the chemical
      analysis which showed an elevated soil Cu content for both sites closest to the
      chemical production company compared to the reference site. The results confirm
      the importance and predictive value of using bioassays in conjunction with
      chemical analysis during soil quality assessments.

PMID- 24875831
TI  - Synthesis of benzofuro[2,3-c]pyridines via a one-pot three-component reaction.
AB  - A convenient one-pot reaction was conducted by mixing bromoacetophenone, a
      functionalized alpha,beta-unsaturated ketone and potassium hydroxide in
      tetrahydrofuran at room temperature, ammonium acetate was added and heated to
      reflux, resulting in four chemical bonds forming from easily accessible
      substrates. This process provides a flexible and rapid synthetic route for the
      construction of polysubstituted benzofuro[2,3-c]pyridines in moderate to good
      yields. 

PMID- 24875828
TI  - A large family of antivirulence regulators modulates the effects of
      transcriptional activators in Gram-negative pathogenic bacteria.
AB  - We have reported that transcription of a hypothetical small open reading frame
      (orf60) in enteroaggregative E. coli (EAEC) strain 042 is impaired after mutation
      of aggR, which encodes a global virulence activator. We have also reported that
      the cryptic orf60 locus was linked to protection against EAEC diarrhea in two
      epidemiologic studies. Here, we report that the orf60 product acts as a negative
      regulator of aggR itself. The orf60 protein product lacks homology to known
      repressors, but displays 44-100% similarity to at least fifty previously
      undescribed small (<10 kDa) hypothetical proteins found in many gram negative
      pathogen genomes. Expression of orf60 homologs from enterotoxigenic E. coli
      (ETEC) repressed the expression of the AraC-transcriptional ETEC regulator
      CfaD/Rns and its regulon in ETEC strain H10407. Complementation in trans of EAEC
      042orf60 by orf60 homologs from ETEC and the mouse pathogen Citrobacter rodentium
      resulted in dramatic suppression of aggR. A C. rodentium orf60 homolog mutant
      showed increased levels of activator RegA and increased colonization of the adult
      mouse. We propose the name Aar (AggR-activated regulator) for the clinically and
      epidemiologically important orf60 product in EAEC, and postulate the existence of
      a large family of homologs among pathogenic Enterobacteriaceae and
      Pasteurellaceae. We propose the name ANR (AraC Negative Regulators) for this
      family. 

PMID- 24875832
TI  - Influence of depth of interaction upon the performance of scintillator detectors.
AB  - The uncertainty in time of particle detection within a scintillator detector,
      characterised by the coincidence time resolution (CTR), is explored with respect
      to the interaction position within the scintillator crystal itself. Electronic
      collimation between two scintillator detectors is utilised to determine the CTR
      with depth of interaction (DOI) for different materials, geometries and
      wrappings. Significantly, no relationship between the CTR and DOI is observed
      within experimental error. Confinement of the interaction position is seen to
      degrade the CTR in long scintillator crystals by 10%.

PMID- 24875833
TI  - Mini-symposium: oxygen and infancy.

PMID- 24875835
TI  - TRUE gene silencing for hematologic malignancies.

PMID- 24875836
TI  - Detection of recent holding of firearms: improving the sensitivity of the PDT
      test.
AB  - Despite the significant improvement of the PDT test for detecting recent contact
      with firearms, there are still many occasions in which the modified reagent
      (FerrotraceTM) shows insufficient sensitivity. Two techniques have been devised
      and tested for the enhancement of the sensitivity of this process: exposure to
      water vapors and accelerated sweating. Exposure of the hand to water vapors after
      spraying with the reagent significantly improved the quality of the colored
      impressions. The average increase was by 1 quality-grade (on an arbitrary scale
      of 4 grades). The technique is very simple and does not require any particular
      skill or equipment. Mechanistic aspects of the process are also discussed. 

PMID- 24875837
TI  - Analysis of chain saw lubricating oils commonly used in Thailand's southern
      border provinces for forensic science purpose.
AB  - In recent years, Thailand's southern border provinces (Malay-Muslim-majority
      border provinces) have become the scene of violence and insurgency. One of the
      attack patterns is the blocking of roads with perennial plants followed by
      planned attacks using improvised explosive devices (IEDs) or weapons on first
      responders. Containers of viscous dark lubricating oil and traces of lubricants
      on the felled trees were usually found at the scene. These were suspected to be
      chain oil lubricant from the chainsaws used to cut down the trees used for the
      roadblock. This work aimed to differentiate the chromatographic patterns of used
      lubricating oils available in automobile repair shops from various locations
      across Thailand's southern border provinces. Lubricating oils were analyzed using
      gas chromatography/flame ionization detector (GC/FID) every two weeks to study
      their variation in chemical compositions over time. The results obtained from
      GC/FID were normalized for differentiation. This included four two-stroke, six
      four-stroke, and three recycled oils. Two lubricating oils found at an incident
      scene were also analyzed and the results compared with the chain oil from five
      seized chainsaws. 

PMID- 24875834
TI  - Mosaic epigenetic dysregulation of ectodermal cells in autism spectrum disorder.
AB  - DNA mutational events are increasingly being identified in autism spectrum
      disorder (ASD), but the potential additional role of dysregulation of the
      epigenome in the pathogenesis of the condition remains unclear. The epigenome is
      of interest as a possible mediator of environmental effects during development,
      encoding a cellular memory reflected by altered function of progeny cells.
      Advanced maternal age (AMA) is associated with an increased risk of having a
      child with ASD for reasons that are not understood. To explore whether AMA
      involves covert aneuploidy or epigenetic dysregulation leading to ASD in the
      offspring, we tested a homogeneous ectodermal cell type from 47 individuals with
      ASD compared with 48 typically developing (TD) controls born to mothers of >=35
      years, using a quantitative genome-wide DNA methylation assay. We show that DNA
      methylation patterns are dysregulated in ectodermal cells in these individuals,
      having accounted for confounding effects due to subject age, sex and ancestral
      haplotype. We did not find mosaic aneuploidy or copy number variability to occur
      at differentially-methylated regions in these subjects. Of note, the loci with
      distinctive DNA methylation were found at genes expressed in the brain and
      encoding protein products significantly enriched for interactions with those
      produced by known ASD-causing genes, representing a perturbation by epigenomic
      dysregulation of the same networks compromised by DNA mutational mechanisms. The
      results indicate the presence of a mosaic subpopulation of epigenetically
      dysregulated, ectodermally-derived cells in subjects with ASD. The epigenetic
      dysregulation observed in these ASD subjects born to older mothers may be
      associated with aging parental gametes, environmental influences during
      embryogenesis or could be the consequence of mutations of the chromatin
      regulatory genes increasingly implicated in ASD. The results indicate that
      epigenetic dysregulatory mechanisms may complement and interact with DNA
      mutations in the pathogenesis of the disorder.

PMID- 24875838
TI  - Historical imagination, narrative learning and nursing practice: graduate nursing
      students' reader-responses to a nurse's storytelling from the past.
AB  - Storytelling and narrative are widely used in nurse education and the value of
      narrative-based curricula, such as those governed by narrative pedagogy, is well
      recognised. Storytelling stimulates students' imagination, a central feature of
      narrative learning. One form of story and imagination yet to be fully considered
      by educators is the historical story and historical imagination. The use of
      historical storytelling creates a temporal dissonance between the story and
      reader that stimulates readers' imagination and response, and enables them to
      gain rich insights which can be applied to the present. Reader-response theory
      can support educators when using narrative and storytelling. This article
      presents an analysis of graduate nursing students' reader-responses to a nurse's
      story from the past. This narrative learning group used their historical
      imagination in responding to the story and prompted and challenged each other in
      their interpretation and in translating their responses to their current nursing
      practice. The article discusses this analysis within the context of reader
      response theory and its potential application to narrative-based learning in
      nurse education. Historical stories stimulate historical imagination and offer a
      different frame of reference for students' development of textual competence and
      for applying insights to the present. 

PMID- 24875839
TI  - Clinical simulation: dare we venture into the uncanny valley?

PMID- 24875840
TI  - The knowledge and attitudes of student nurses towards patients with sexually
      transmitted infections: exploring changes to the curriculum.
AB  - Evidence suggests that nurses can struggle to care for patients with sexually
      transmitted infections in a non-judgemental way. It is unknown how targeted
      education can influence the knowledge and attitudes of student nurses towards
      caring for patients with sexually transmitted infections. This study aimed to
      investigate how a change in curriculum influenced the reported sexual health
      knowledge and attitudes of pre-registration adult student nurses in a University
      in the UK. A two phase mixed methods study, using a sequential explanatory
      strategy, collected quantitative questionnaire data (n = 117) followed by
      qualitative group data (n = 12). Data were collected from one cohort of students
      before a curriculum change and then from a subsequent cohort of students. Those
      students who had increased educational input in relation to sexual health
      reported higher degrees of knowledge and demonstrated a more positive attitude
      towards patients with a sexually transmitted infection. Both cohorts of students
      identified that education in this subject area was essential to challenge
      negative attitudes and positively influence patient care. Active learning
      approaches in the curriculum such as small group debates and service user
      involvement have the ability to allow students to express and challenge their
      beliefs in a safe and supportive environment.

PMID- 24875842
TI  - Idiopathic pulmonary fibrosis in the USA.

PMID- 24875841
TI  - Idiopathic pulmonary fibrosis in US Medicare beneficiaries aged 65 years and
      older: incidence, prevalence, and survival, 2001-11.
AB  - BACKGROUND: Published data for the epidemiology of idiopathic pulmonary fibrosis
      in the USA are scarce. We sought to estimate the incidence, prevalence, and
      mortality risk of idiopathic pulmonary fibrosis among US Medicare beneficiaries.
      METHODS: We used administrative claims from a 5% random sample of Medicare
      beneficiaries (aged 65 years and older) from the years 2000-11 as a data source.
      Idiopathic pulmonary fibrosis was defined by International Classification of
      Diseases, Ninth Revision, Clinical Modification diagnosis codes. We estimated
      annual incidence and cumulative prevalence of idiopathic pulmonary fibrosis,
      median survival time of patients, and potential risk factors for diagnosis of
      idiopathic pulmonary fibrosis and death between 2001 and 2011. We also estimated
      incidence and prevalence using more restrictive algorithms for diagnosis.
      FINDINGS: The annual incidence of idiopathic pulmonary fibrosis in the Medicare
      population remained stable between 2001 and 2011, with an overall estimate of
      93.7 cases per 100000 person-years (95% CI 91.9-95.4) across the study period.
      The annual cumulative prevalence increased steadily from 202.2 cases per 100000
      people in 2001 to 494.5 cases per 100000 people in 2011. Among newly diagnosed
      patients with Medicare (mean age 79.4 years [SD 7.2], 54% female, 91% white), the
      median survival time was 3.8 years (95% CI 3.5-3.8). Older age and male sex were
      associated with a higher incidence of disease and shorter survival time after
      diagnosis. Mortality risk was lower in patients diagnosed in more recent years
      (median survival time 3.3 years [95% CI 3.0-3.8] in 2001 vs 4.0 years [3.8-4.5]
      in 2007). INTERPRETATION: The incidence and prevalence of idiopathic pulmonary
      fibrosis in people aged 65 years and older in the USA are substantially higher
      than previously reported, and prevalence is increasing annually, even in the
      subgroups based on more restrictive algorithms for diagnosis. Patients with
      idiopathic pulmonary fibrosis aged 65 years and older were living longer in 2011
      than they were 10 years before, which could partly account for the steady
      increase in prevalence. FUNDING: Biogen Idec.

PMID- 24875843
TI  - Topotactic condensation of layer silicates with ferrierite-type layers forming
      porous tectosilicates.
AB  - Five different hydrous layer silicates (HLSs) containing fer layers (ferrierite
      type layers) were obtained by hydrothermal syntheses from mixtures of silicic
      acid, water and tetraalkylammonium/tetraalkylphosphonium hydroxides. The organic
      cations had been added as structure directing agents (SDA). A characteristic
      feature of the structures is the presence of strong to medium strong hydrogen
      bonds between the terminal silanol/siloxy groups of neighbouring layers. The five
      layered silicates differ chemically only with respect to the organic cations.
      Structurally, they differ with respect to the arrangement of the fer layers
      relative to each other, which is distinct for every SDA-fer-layer system. RUB-20
      (containing tetramethylammonium) and RUB-40 (tetramethylphosphonium) are
      monoclinic with stacking sequence AAA and shift vectors between successive layers
      1a0 + 0b0 + 0.19c0 and 1a0 + 0b0 + 0.24c0, respectively. RUB-36
      (diethyldimethylammonium), RUB-38 (methyltriethylammonium) and RUB-48
      (trimethylisopropylammonium) are orthorhombic with stacking sequence ABAB and
      shift vectors 0.5a0 + 0b0+/- 0.36c0, 0.5a0 + 0b0 + 0.5c0 and 0.5a0 + 0b0+/-
      0.39c0, respectively. Unprecedented among the HLSs, two monoclinic materials are
      made up of fer layers which possess a significant amount of ordered defects
      within the layer. The ordered defects involve one particular Si-O-Si bridge which
      is, to a fraction of ca. 50%, hydrolyzed to form nests of two =Si-OH groups. When
      heated to 500-600  degrees C in air, the HLSs condense to form framework
      silicates. Although all layered precursors were moderately to well ordered, the
      resulting framework structures were of quite different crystallinity. The
      orthorhombic materials RUB-36, -38 and -48, general formula SDA4Si36O72(OH)4,
      which possess very strong hydrogen bonds (d[O...O] ~ 2.4 A), transform into a
      fairly or well ordered CDO-type silica zeolite RUB-37. The monoclinic materials
      RUB-20 and -40, general formula SDA2Si18O36(OH)2OH, possessing medium strong
      hydrogen bonds (d[O...O] ~ 2.65 A) are transformed into poorly ordered framework
      silicates. Some rules of thumb can be established concerning the successful
      zeolite synthesis via a topotactic condensation of layered precursors.
      Favourably, the precursor (i) possesses already a well ordered structure without
      defects, (ii) contains strong inter-layer hydrogen bonds and does not contain
      strong intra-layer hydrogen bonds and (iii) contains a suitable cation. The
      nature of the organic cation (size, geometry, flexibility, thermal stability)
      plays a key role in the formation of a microporous tectosilicate with well
      ordered structure. RUB-36 which meets these criteria yields a well ordered
      condensation product (RUB-37).

PMID- 24875846
TI  - Opiate binding to brain slices and ontogenesis of hypothalamic [(3)H]naloxone
      binding sites.
AB  - We have developed a radioligand binding assay based on the use of hypothalamic
      slices and have examined the ontogenesis of [(3)H]naloxone binding sites in male
      and female rats. [(3)H]NAL binding is reversible, saturable, stereospecific, of
      high affinity, readily displaceable by morphine and is sensitive to
      phenoxybenzamine. These characteristics suggest that [(3)H]NAL readily binds to
      opiate receptors in brain slices. With this assay we have demonstrated that: (a)
      there is an age-related increase in opiate binding sites in rat hypothalamus, (b)
      there are sex differences in the binding affinity of the sites and (c) the values
      of Bmax are approximately 2-5-fold higher than the levels previously reported
      from assays with brain homogenates. 

PMID- 24875845
TI  - Changes in the morphology and proliferation of astrocytes induced by two
      modalities of chemically functionalized single-walled carbon nanotubes are
      differentially mediated by glial fibrillary acidic protein.
AB  - Alterations in glial fibrillary acidic protein (GFAP) levels accompany the
      changes in the morphology and proliferation of astrocytes induced by colloidal
      solutes and films of carbon nanotubes (CNTs). To determine if GFAP is required
      for the effects of CNTs on astrocytes, we used astrocytes isolated from GFAP null
      mice. We find that selected astrocytic changes induced by CNTs are mediated by
      GFAP, i.e., perimeter, shape, and cell death for solutes, and proliferation for
      films. 

PMID- 24875847
TI  - Influence of nerve growth factor on developing dorso-medial and ventro-lateral
      neurons of chick and mouse trigeminal ganglia.
AB  - Trigeminal ganglia have been removed from five, six, seven and eight day chick
      embryos and explants of the dorso-medial (DM) and ventro-lateral (VL) parts of
      the maxillomandibular lobe were grown in tissue culture. Quantitative methods
      were used to assess the influence of nerve growth factor (NGF) on fiber outgrowth
      from these explants. At all ages outgrowth from DM explants was significantly
      greater than from VL explants, the difference being most pronounced between the
      extreme DM and VL poles of the maxillomandibular lobe. These observations are
      interpreted as indicating the existence of two distinct populations of neurons in
      terms of their response to NGF rather than the consequence of the asynchronous
      differentiation and maturation of the VL and DM neurons. A similar study of 10,
      11 and 12 day embryonic mouse trigeminal ganglia revealed no significant
      difference in neurite outgrowth between DM and VL regions grown in the presence
      or absence of NGF. 

PMID- 24875844
TI  - Characterisation of the vaginal Lactobacillus microbiota associated with preterm
      delivery.
AB  - The presence of an abnormal vaginal microflora in early pregnancy is a risk
      factor for preterm delivery. There is no investigation on vaginal flora dominated
      by lactic acid bacteria and possible association with preterm delivery. We
      assessed the dominant vaginal Lactobacillus species in healthy pregnant women in
      early pregnancy in relation to pregnancy outcome. We observed 111 low risk
      pregnant women with a normal vaginal microflora 11 + 0 to 14 + 0 weeks of
      pregnancy without subjective complaints. Vaginal smears were taken for the
      identification of lactobacilli using denaturing gradient gel electrophoresis
      (DGGE). Pregnancy outcome was recorded as term or preterm delivery (limit 36 + 6
      weeks of gestation). The diversity of Lactobacillus species in term vs. preterm
      was the main outcome measure. L. iners alone was detected in 11 from 13 (85%)
      women who delivered preterm. By contrast, L. iners alone was detected in only 16
      from 98 (16%) women who delivered at term (p < 0.001). Fifty six percent women
      that delivered at term and 8% women that delivered preterm had two or more
      vaginal Lactobacillus spp. at the same time. This study suggests that dominating
      L. iners alone detected in vaginal smears of healthy women in early pregnancy
      might be associated with preterm delivery. 

PMID- 24875848
TI  - Polyamine acetylation in the developing and aging mouse brain.
AB  - Putrescine and spermidine acetylation is at least 10-fold higher in the brain
      homogenate of the neonate (1-day-old) mouse than in the adult (90 days old).
      Although the pattern of putrescine and spermidine acetylation is similar
      throughout development, the acetylation of spermidine is consistently higher. As
      the animal matures, the activity curves tend to converge. In the P1 (crude
      nuclei) and microsomal fractions, the acetylation of spermidine is highest at day
      1, while putrescine acetylation peaks at day 4. In contrast to the adult animal,
      putrescine and spermidine acetylation are present in the P2 (crude mitochondria)
      and soluble fractions. In the P2 fraction, spermidine acetylation is highest at
      birth, while the acetylation of putrescine peaks at day 3. Acetylation of both
      substrates is barely detectable by day 42. In the soluble fraction, putrescine
      and spermidine acetylation show the highest activity at day 5. The activity
      declined towards adult values by day 10 in all the fractions examined.
      Acetylation of putrescine and spermidine is approximately 4-fold higher in the
      brain homogenate of the 120-day-old mouse than in that of the 90-day-old mouse.
      Both the acetylation of putrescine and spermidine decline as the animal grows
      older. In contrast to the perinatal period (day 20 of gestation to 4 days old)
      the acetylation of putrescine is almost identical to that of spermidine in the
      adult mouse. These results suggest that polyamine acetylation may play an
      important role in polyamine metabolism in the developing mouse brain. The
      presence of activity in the P2 and soluble fractions of the neonatal, but not
      adult mouse brain, suggests that putrescine, via acetylputrescine, may contribute
      to the GABA levels during development. 

PMID- 24875849
TI  - Hypothalamic testosterone increase in the male rat at birth.
AB  - In the male rat, a dramatic increase in serum testosterone occurs during the
      first 2 h of postnatal life. Since the hypothalamus is known to be an important
      site for sexual differentiation of the brain, this early testosterone surge was a
      good model to use to study the transfer of serum testosterone to the hypothalamus
      and cerebral cortex. Endogenous testosterone was measured by radioimmunoassay in
      the hypothalamus and the cerebral cortex of the foetus and newborn rats during
      the first 6 h following birth. In the male, hypothalamic testosterone increased
      between 0 h in utero and 2 h; in the males gonadectomized at 0 h in utero and
      killed at the age of 2 h, the testosterone surge was abolished, clearly
      indicating the testicular origin of this hormone in the neonate. The small
      testosterone increase in the cerebral cortex compared with that in the
      hypothalamus reflects a preferential uptake of this hormone by the hypothalamus
      of the newborn. In the female, hypothalamic testosterone slightly decreased
      between 0 h in utero and 6 h. These results are in agreement with the view that
      hypothalamic modifications form the basis for some behavioral and physiological
      changes attributed to the effect of perinatal hormonal stimulation. 

PMID- 24875851
TI  - Teaching minority children hygiene: investigating hygiene education in
      kindergartens and homes of ethnic minority children in northern Vietnam.
AB  - OBJECTIVES: Ethnic minority children in Vietnam experience high levels of hygiene
      and sanitation-related diseases. Improving hygiene for minority children is
      therefore vital for improving child health. The study objective was to
      investigate how kindergarten and home environments influence the learning of
      hygiene of pre-school ethnic minority children in rural Vietnam. DESIGN: Eight
      months of ethnographic field studies were conducted among four ethnic minority
      groups living in highland and lowland communities in northern Vietnam. Data
      included participant observation in four kindergartens and 20 homes of pre-school
      children, together with 67 semi-structured interviews with caregivers and five
      kindergarten staff. Thematic analysis was applied and concepts of social learning
      provided inputs to the analysis. FINDINGS: This study showed that poor living
      conditions with lack of basic sanitation infrastructures were important barriers
      for the implementation of safe home child hygiene. Furthermore, the everyday life
      of highland villages, with parents working away from the households resulted in
      little daily adult supervision of safe child hygiene practices. While
      kindergartens were identified as potentially important institutions for improving
      child hygiene education, essential and well-functioning hygiene infrastructures
      were lacking. Also, hygiene teaching relied on theoretical and non-practice-based
      learning styles, which did not facilitate hygiene behaviour change in small
      children. Minority children were further disadvantaged as teaching was only
      provided in non-minority language. CONCLUSIONS: Kindergartens can be important
      institutions for the promotion of safe hygiene practices among children, but they
      must invest in the maintenance of hygiene and sanitation infrastructures and
      adopt a strong practice-based teaching approach in daily work and in teacher's
      education. To support highland minority children in particular, teaching styles
      must take local living conditions and caregiver structures into account and teach
      in local languages. Creating stronger links between home and institutional
      learning environments can be vital to support disadvantaged highland families in
      improving child health.

PMID- 24875852
TI  - Recent insights on the significance of transcriptomic and metabolomic analysis of
      male factor infertility.
AB  - Infertility is a worldwide reproductive health problem which affects
      approximately 15% of couples, with male factor infertility dominating nearly 50%
      of the affected population. The nature of the phenomenon is underscored by a
      complex array of transcriptomic, proteomic and metabolic differences which
      interact in unknown ways. Many causes of male factor infertility are still
      defined as idiopathic, and most diagnosis tends to be more descriptive rather
      than specific. As such, the emergence of novel transcriptomic and metabolomic
      studies may hold the key to more accurately diagnose and treat male factor
      infertility. This paper provides the most recent evidence underlying the role of
      transcriptomic and metabolomic analysis in the management of male infertility. A
      summary of the current knowledge and new discovery of noninvasive, highly
      sensitive and specific biomarkers which allow the expansion of this area is
      outlined. 

PMID- 24875850
TI  - Nucleotide-type chemical shift assignment of the encapsulated 40 kbp dsDNA in
      intact bacteriophage T7 by MAS solid-state NMR.
AB  - The icosahedral bacteriophage T7 is a 50 MDa double-stranded DNA (dsDNA) virus
      that infects Escherichia coli. Although there is substantial information on the
      physical and morphological properties of T7, structural information, based mostly
      on Raman spectroscopy and cryo-electron microscopy, is limited. Here, we apply
      the magic-angle spinning (MAS) solid-state NMR (SSNMR) technique to study a
      uniformly (13)C and (15)N labeled wild-type T7 phage. We describe the details of
      the large-scale preparation and purification of an isotopically enriched phage
      sample under fully hydrated conditions, and show a complete (13)C and a near
      complete (15)N nucleotide-type specific assignment of the sugar and base moieties
      in the 40 kbp dsDNA of T7 using two-dimensional (13)C-(13)C and (15)N-(13)C
      correlation experiments. The chemical shifts are interpreted as reporters of a B
      form conformation of the encapsulated dsDNA. While MAS SSNMR was found to be
      extremely useful in determining the structures of proteins in native-like
      environments, its application to nucleic acids has lagged behind, leaving a
      missing (13)C and (15)N chemical shift database. This work therefore expands the
      (13)C and (15)N database of real B-form DNA systems, and opens routes to
      characterize more complex nucleic acid systems by SSNMR. 

PMID- 24875853
TI  - Histoplasmosis mimicking malignant adenopathy during diagnostic thyroid
      lobectomy.
AB  - IMPORTANCE: Benign granulomatous disease may mimic malignant disease in the
      evaluation of mediastinal or pulmonary lesions. However, histoplasmosis as a
      cause of cervical lymphadenopathy is relatively rare. We report the first case of
      Histoplasma infection mimicking malignant adenopathy discovered during diagnostic
      thyroid lobectomy. OBSERVATIONS: A 2.5-cm, calcified, right paratracheal lymph
      node intimately involving the recurrent laryngeal nerve was discovered during
      lobectomy for a follicular lesion of undetermined significance with a positive
      NRAS mutation. Although metastatic thyroid cancer was the most probable
      diagnosis, results of gross inspection of the bisected thyroid nodule suggested a
      benign process. Partial removal of the node, sparing the nerve, established the
      diagnosis of Histoplasma capsulatum infection. CONCLUSIONS AND RELEVANCE:
      Histoplasmosis is a rare cause of cervical adenopathy that should be considered
      in cases in which a discordance arises between the malignant gross appearance of
      the adenopathy and the benign gross appearance of an associated thyroid nodule.

PMID- 24875854
TI  - A recyclable and reusable supported Cu(I) catalyzed azide-alkyne click
      polymerization.
AB  - The azide-alkyne click polymerization (AACP) has emerged as a powerful tool for
      the synthesis of functional polytriazoles. While, for the Cu(I)-catalyzed AACP,
      the removal of the catalytic Cu(I) species from the resulting polytriazoles is
      difficult, and the research on the recyclability and reusability of the catalyst
      remains intact. Herein, we reported the first example of using recyclable and
      reusable supported Cu(I) catalyst of CuI@A-21 for the AACP. CuI@A-21 could not
      only efficiently catalyze the AACP but also be reused for at least 4 cycles.
      Moreover, pronounced reduction of copper residues in the products was achieved.
      Apart from being a green and cost-effective polymer synthesis strategy, this
      method will also broaden the application of AACP in material and biological
      sciences and provide guidelines for other polymerizations with metal catalysts. 

PMID- 24875855
TI  - The Touch and Zap method for in vivo whole-cell patch recording of intrinsic and
      visual responses of cortical neurons and glial cells.
AB  - Whole-cell patch recording is an essential tool for quantitatively establishing
      the biophysics of brain function, particularly in vivo. This method is of
      particular interest for studying the functional roles of cortical glial cells in
      the intact brain, which cannot be assessed with extracellular recordings.
      Nevertheless, a reasonable success rate remains a challenge because of stability,
      recording duration and electrical quality constraints, particularly for voltage
      clamp, dynamic clamp or conductance measurements. To address this, we describe
      "Touch and Zap", an alternative method for whole-cell patch clamp recordings,
      with the goal of being simpler, quicker and more gentle to brain tissue than
      previous approaches. Under current clamp mode with a continuous train of
      hyperpolarizing current pulses, seal formation is initiated immediately upon cell
      contact, thus the "Touch". By maintaining the current injection, whole-cell
      access is spontaneously achieved within seconds from the cell-attached
      configuration by a self-limited membrane electroporation, or "Zap", as seal
      resistance increases. We present examples of intrinsic and visual responses of
      neurons and putative glial cells obtained with the revised method from cat and
      rat cortices in vivo. Recording parameters and biophysical properties obtained
      with the Touch and Zap method compare favourably with those obtained with the
      traditional blind patch approach, demonstrating that the revised approach does
      not compromise the recorded cell. We find that the method is particularly well
      suited for whole-cell patch recordings of cortical glial cells in vivo, targeting
      a wider population of this cell type than the standard method, with better access
      resistance. Overall, the gentler Touch and Zap method is promising for studying
      quantitative functional properties in the intact brain with minimal perturbation
      of the cell's intrinsic properties and local network. Because the Touch and Zap
      method is performed semi-automatically, this approach is more reproducible and
      less dependent on experimenter technique. 

PMID- 24875856
TI  - The evolution of morphospace in phytophagous scarab chafers: no competition--no
      divergence?
AB  - Body shape reflects species' evolution and mediates its role in the environment
      as it integrates gene expression, life style, and structural morphology. Its
      comparative analysis may reveal insight on what shapes shape, being a useful
      approach when other evidence is lacking. Here we investigated evolutionary
      patterns of body shape in the highly diverse phytophagous chafers (Scarabaeidae:
      Pleurosticti), a polyphagous group utilizing different parts of angiosperms.
      Because the reasons of their successful diversification are largely unknown, we
      used a phylogenetic tree and multivariate analysis on twenty linear measurements
      of body morphology including all major Pleurosticti lineages to infer patterns of
      morphospace covariation and divergence. The chafer's different feeding types
      resulted to be not distinguishable in the described morphospace which was largely
      attributed to large occupancy of the morphospace of some feeding types and to
      multiple convergences of feeding behavior (particularly of anthophagy). Low
      correlation between molecular and morphological rates of evolution, including
      significant rate shifts for some lineages, indicated directed selection within
      feeding types. This is supported by morphospace divergence within feeding types
      and convergent evolution in Australian Melolonthinae. Traits driving morphospace
      divergence were extremities and traits linked with locomotion behavior, but also
      body size. Being highly adaptive for burrowing and locomotion these traits showed
      major changes in the evolution of pleurostict scarabs. These activities also
      affected another trait, the metacoxal length, which is highly influenced by key
      innovations of the metacoxa (extended mesal process, secondary closure)
      particularly in one lineage, the Sericini. Significant shape divergence between
      major lineages and a lack of strong differentiation among closely related
      lineages indicated that the question about the presence or absence of competition
      derived directed selection needs to be addressed for different time scales.
      Striking divergence between some sister lineages at their origin revealed strong
      driven selection towards morphospace divergence, possibly linked with resource
      partitioning. 

PMID- 24875857
TI  - Autophagy is required for glucose homeostasis and lung tumor maintenance.
AB  - Macroautophagy (autophagy hereafter) recycles intracellular components to sustain
      mitochondrial metabolism that promotes the growth, stress tolerance, and
      malignancy of lung cancers, suggesting that autophagy inhibition may have
      antitumor activity. To assess the functional significance of autophagy in both
      normal and tumor tissue, we conditionally deleted the essential autophagy gene,
      autophagy related 7 (Atg7), throughout adult mice. Here, we report that systemic
      ATG7 ablation caused susceptibility to infection and neurodegeneration that
      limited survival to 2 to 3 months. Moreover, upon fasting, autophagy-deficient
      mice suffered fatal hypoglycemia. Prior autophagy ablation did not alter the
      efficiency of non-small cell lung cancer (NSCLC) initiation by activation of
      oncogenic Kras(G12D) and deletion of the Trp53 tumor suppressor. Acute autophagy
      ablation in mice with preexisting NSCLC, however, blocked tumor growth, promoted
      tumor cell death, and generated more benign disease (oncocytomas). This antitumor
      activity occurred before destruction of normal tissues, suggesting that acute
      autophagy inhibition may be therapeutically beneficial in cancer. SIGNIFICANCE:
      We systemically ablated cellular self-cannibalization by autophagy in adult mice
      and determined that it is dispensable for short-term survival, but required to
      prevent fatal hypoglycemia and cachexia during fasting, delineating a new role
      for autophagy in metabolism. Importantly, acute, systemic autophagy ablation was
      selectively destructive to established tumors compared with normal tissues,
      thereby providing the preclinical evidence that strategies to inhibit autophagy
      may be therapeutically advantageous for RAS-driven cancers.

PMID- 24875859
TI  - Inflammatory myofibroblastic tumors harbor multiple potentially actionable kinase
      fusions.
AB  - Inflammatory myofibroblastic tumor (IMT) is a neoplasm that typically occurs in
      children. The genetic landscape of this tumor is incompletely understood and
      therapeutic options are limited. Although 50% of IMTs harbor anaplastic lymphoma
      kinase (ALK) rearrangements, no therapeutic targets have been identified in ALK
      negative tumors. We report for the first time that IMTs harbor other actionable
      targets, including ROS1 and PDGFRbeta fusions. We detail the case of an 8-year
      old boy with treatment-refractory ALK-negative IMT. Molecular tumor profiling
      revealed a ROS1 fusion, and he had a dramatic response to the ROS1 inhibitor
      crizotinib. This case prompted assessment of a larger series of IMTs. Next
      generation sequencing revealed that 85% of cases evaluated harbored kinase
      fusions involving ALK, ROS1, or PDGFRbeta. Our study represents the most
      comprehensive genetic analysis of IMTs to date and also provides a rationale for
      routine molecular profiling of these tumors to detect therapeutically actionable
      kinase fusions. SIGNIFICANCE: Our study describes the most comprehensive genomics
      based evaluation of IMT to date. Because there is no "standard-of-care" therapy
      for IMT, the identification of actionable genomic alterations, in addition to
      ALK, is expected to redefine management strategies for patients with this
      disease.

PMID- 24875858
TI  - NSD3-NUT fusion oncoprotein in NUT midline carcinoma: implications for a novel
      oncogenic mechanism.
AB  - NUT midline carcinoma (NMC) is an aggressive subtype of squamous cell carcinoma
      that typically harbors BRD4/3-NUT fusion oncoproteins that block differentiation
      and maintain tumor growth. In 20% of cases, NUT is fused to uncharacterized non
      BRD gene(s). We established a new patient-derived NMC cell line (1221) and
      demonstrated that it harbors a novel NSD3-NUT fusion oncogene. We find that NSD3
      NUT is both necessary and sufficient for the blockade of differentiation and
      maintenance of proliferation in NMC cells. NSD3-NUT binds to BRD4, and BRD
      bromodomain inhibitors induce differentiation and arrest proliferation of 1221
      cells. We find further that NSD3 is required for the blockade of differentiation
      in BRD4-NUT-expressing NMCs. These findings identify NSD3 as a novel critical
      oncogenic component and potential therapeutic target in NMC. SIGNIFICANCE: The
      existence of a family of fusion oncogenes in squamous cell carcinoma is
      unprecedented, and should lead to key insights into aberrant differentiation in
      NMC and possibly other squamous cell carcinomas. The involvement of the NSD3
      methyltransferase as a component of the NUT fusion protein oncogenic complex
      identifies a new potential therapeutic target.

PMID- 24875861
TI  - Venous endothelin guides sympathetic innervation of the developing mouse heart.
AB  - The mechanisms responsible for establishing correct target innervation during
      organ development are largely unknown. Sympathetic nerves follow blood vessels-
      typically arteries--to reach their endorgans, suggesting the existence of
      vascular guidance cues that direct axonal extension. The sinoatrial node and the
      ventricle of the heart receive sympathetic innervation from the stellate ganglia
      (STG). Here we show that STG axons follow veins, specifically the superior vena
      cavae and sinus venosus, to reach these targets. We find that election of these
      routes is determined by venous endothelium-derived endothelin-1, acting through
      its specific receptor Ednra expressed within a subpopulation of STG neurons.
      Furthermore, we demonstrate that Edn1-Ednra signalling is essential for
      functional regulation of the heart by sympathetic nerves. Our findings present
      venous Edn1 as a sympathetic guidance cue, and show how axon guidance mechanisms
      are coordinated with endorgan morphogenesis.

PMID- 24875862
TI  - Breast cancer screening among women of child-bearing age.
AB  - We explored behavioral factors that contributed to late presentation of breast
      cancer. A cross-sectional survey of 120 women of child-bearing age was employed,
      and data were collected using interviewer-administered questionnaires addressing
      predisposing, enabling, and reinforcing factors associated with breast cancer
      screening. A total of 53.5% knew what breast cancer screening was; breast self
      exam was the most commonly known form of screening, although only 7.5% practiced
      it. Lack of awareness (p =.004) and the knowledge of someone who previously had
      breast cancer (p =.0004) were prominent predictors for breast cancer screening,
      leading to either delay in or early presentation of the condition, respectively. 

PMID- 24875860
TI  - Autophagy is critical for pancreatic tumor growth and progression in tumors with
      p53 alterations.
AB  - Pancreatic ductal adenocarcinoma is refractory to available therapies. We have
      previously shown that these tumors have elevated autophagy and that inhibition of
      autophagy leads to decreased tumor growth. Using an autochthonous model of
      pancreatic cancer driven by oncogenic Kras and the stochastic LOH of Trp53, we
      demonstrate that although genetic ablation of autophagy in the pancreas leads to
      increased tumor initiation, these premalignant lesions are impaired in their
      ability to progress to invasive cancer, leading to prolonged survival. In
      addition, mouse pancreatic cancer cell lines with differing p53 status are all
      sensitive to pharmacologic and genetic inhibition of autophagy. Finally, a mouse
      preclinical trial using cohorts of genetically characterized patient-derived
      xenografts treated with hydroxychloroquine showed responses across the collection
      of tumors. Together, our data support the critical role of autophagy in
      pancreatic cancer and show that inhibition of autophagy may have clinical utility
      in the treatment of these cancers, independent of p53 status. SIGNIFICANCE:
      Recently, a mouse model with embryonic homozygous Trp53 deletion showed
      paradoxical effects of autophagy inhibition. We used a mouse model with Trp53 LOH
      (similar to human tumors), tumor cell lines, and patient-derived xenografts to
      show that p53 status does not affect response to autophagy inhibition. These
      findings have important implications on ongoing clinical trials.

PMID- 24875863
TI  - The identification of metallothionein in rare minnow (Gobiocypris rarus) and its
      expression following heavy metal exposure.
AB  - Heavy metal, such as cadmium (Cd), lead (Pb) and copper (Cu) poses serious toxin
      to aquatic organisms. These exogenous materials affect biological processes
      including physiology, biochemistry and development. Metallothionein (MT), one of
      the metal-regulated genes, participates in regulating essential and detoxifying
      non-essential metals in living animals. In this study, MT EST in rare minnow
      (Gobiocypris rarus) (GrMT) was obtained from the cDNA subtraction library and the
      GrMT cDNA was firstly cloned by RACE with a sequence of 379 bp, which can code 60
      amino acids. After Cd exposure, the GrMT expression levels dramatically changed
      in liver, spleen, gill, kidney, intestine, but moderately in muscle.
      Significantly positive relationships were found between Cd dosages and MT
      expression levels in liver. And there distinction existed at the GrMT transcript
      level in fish gender and developmental stages during Cd exposure. While Pb
      exposure, the expression alteration happened in spleen, gill, intestine, muscle,
      and moderately in liver. In the Cu treatment test, there were slight changes in
      intestine and kidney, but more significant changes occurred in spleen, gill,
      muscle, and liver. This study had investigated the effects of diverse heavy
      metals on GrMT expression patterns. The results suggest that GrMT would be a
      potential biomarker to metal contamination monitoring in aquatic environments and
      rare minnow could be one of the perfect experimental fishes for surveying the
      freshwater pollution in China.

PMID- 24875864
TI  - Atmospheric reactions of 9,10-anthraquinone.
AB  - The probably carcinogenic compound 9,10-anthraquinone is mainly existing in the
      atmosphere in the particulate phase and is often detected and measured among
      other oxygenated PAHs in atmospheric samples. Its fate, once released or formed
      in the atmosphere, still remains unknown. In this work, heterogeneous chemical
      oxidation processes of 9,10-anthraquinone were investigated with ozone (O3),
      nitrogen dioxide (NO2) and hydroxyl radical (OH). The study of 9,10-anthraquinone
      adsorbed on silica particles showed no reactivity with O3 and NO2. On the other
      hand, the reaction with OH radicals was observed and led to the formation of 1
      hydroxy-9,10-anthraquinone, another oxidation product recognized as possibly
      carcinogenic to humans. This study showed that reactions with ozone and nitrogen
      dioxide are unlikely to contribute to atmospheric degradation of 9,10
      anthraquinone, whereas reactions with OH radicals could be involved in 9,10
      anthraquinone degradation processes, even if such reaction is probably very slow
      under ambient conditions. 

PMID- 24875865
TI  - Effect of long-term phosphorus fertilization on soil Se and transfer of soil Se
      to crops in northern Japan.
AB  - Phosphorus (P) fertilizer can potentially serve as a source for Se accumulation
      in croplands. Furthermore, it has been reported that the addition of P fertilizer
      to soil may enhance Se availability. Japanese agricultural soils are typically
      enriched in P as a result of long-term, excessive P fertilization. Therefore, we
      conducted a three-year field experiment in order to evaluate the effect of P
      fertilization on the Se content of soils and crops. Potato, wheat and barley were
      cultivated with and without P fertilization at two field sites in Hokkaido
      (northern Japan) with different levels of historical P accumulation. The first
      field site consisted of an Andosol soil with low available P and the second site,
      a Cambisol soil with high available P. The three years of continuous P
      fertilization over the course of the experiment did not result in a significant
      increase in the Se content of soils or plants. The Se content of soils and
      plants, however, was higher in soil samples from the Cambisol field site than
      from the Andosol field site, and total soil Se was significantly correlated with
      available soil P. Soluble soil Se and the soil-plant transfer factor for Se were
      not affected by P fertilization. Thus, we concluded that the higher plant Se
      content at the Cambisol field site was primarily due to the higher levels of
      accumulated Se in the soil at the site and that historical excess P fertilization
      typical of agricultural soils in Japan contributes to increased Se uptake by
      crops. 

PMID- 24875866
TI  - Role of submerged vegetation in the retention processes of three plant protection
      products in flow-through stream mesocosms.
AB  - Quantitative information on the processes leading to the retention of plant
      protection products (PPPs) in surface waters is not available, particularly for
      flow-through systems. The influence of aquatic vegetation on the hydraulic- and
      sorption-mediated mitigation processes of three PPPs (triflumuron, pencycuron,
      and penflufen; logKOW 3.3-4.9) in 45-m slow-flowing stream mesocosms was
      investigated. Peak reductions were 35-38% in an unvegetated stream mesocosm, 60
      62% in a sparsely vegetated stream mesocosm (13% coverage with Elodea nuttallii),
      and in a similar range of 57-69% in a densely vegetated stream mesocosm (100%
      coverage). Between 89% and 93% of the measured total peak reductions in the
      sparsely vegetated stream can be explained by an increase of vegetation-induced
      dispersion (estimated with the one-dimensional solute transport model OTIS),
      while 7-11% of the peak reduction can be attributed to sorption processes.
      However, dispersion contributed only 59-71% of the peak reductions in the densely
      vegetated stream mesocosm, where 29% to 41% of the total peak reductions can be
      attributed to sorption processes. In the densely vegetated stream, 8-27% of the
      applied PPPs, depending on the logKOW values of the compounds, were temporarily
      retained by macrophytes. Increasing PPP recoveries in the aqueous phase were
      accompanied by a decrease of PPP concentrations in macrophytes indicating kinetic
      desorption over time. This is the first study to provide quantitative data on how
      the interaction of dispersion and sorption, driven by aquatic macrophytes,
      influences the mitigation of PPP concentrations in flowing vegetated stream
      systems. 

PMID- 24875867
TI  - Characteristics of volatile organic compounds emission profiles from hot road
      bitumens.
AB  - A procedure for the investigation and comparison of volatile organic compounds
      (VOCs) emission profiles to the atmosphere from road bitumens with various
      degrees of oxidation is proposed. The procedure makes use of headspace analysis
      and gas chromatography with universal as well as selective detection, including
      gas chromatography-mass spectrometry (GC-MS). The studies revealed that so-called
      vacuum residue, which is the main component of the charge, contains variable VOC
      concentrations, from trace to relatively high ones, depending on the extent of
      thermal cracking in the boiler of the vacuum distillation column. The VOC content
      in the oxidation product, so-called oxidized paving bitumen, is similarly varied.
      There are major differences in VOC emission profiles between vacuum residue and
      oxidized bitumens undergoing thermal cracking. The VOC content in oxidized
      bitumens, which did not undergo thermal cracking, increases with the degree of
      oxidation of bitumens. The studies revealed that the total VOC content increases
      from about 120 ppm for the raw vacuum residue to about 1900 ppm for so-called
      bitumen 35/50. The amount of volatile sulfur compounds (VSCs) in the volatile
      fraction of fumes of oxidized bitumens increases with the degree of oxidation of
      bitumen and constitutes from 0.34% to 3.66% (w/w). The contribution of volatile
      nitrogen compounds (VNCs) to total VOC content remains constant for the
      investigated types of bitumens (from 0.16 to 0.28% (w/w) of total VOCs). The
      results of these studies can also find use during the selection of appropriate
      bitumen additives to minimize their malodorousness. The obtained data append the
      existing knowledge on VOC emission from oxidized bitumens. They should be
      included in reports on the environmental impact of facilities in which hot
      bitumen binders are used.

PMID- 24875868
TI  - Electrokinetic-enhanced bioremediation of organic contaminants: a review of
      processes and environmental applications.
AB  - There is current interest in finding sustainable remediation technologies for the
      removal of contaminants from soil and groundwater. This review focuses on the
      combination of electrokinetics, the use of an electric potential to move organic
      and inorganic compounds, or charged particles/organisms in the subsurface
      independent of hydraulic conductivity; and bioremediation, the destruction of
      organic contaminants or attenuation of inorganic compounds by the activity of
      microorganisms in situ or ex situ. The objective of the review is to examine the
      state of knowledge on electrokinetic bioremediation and critically evaluate
      factors which affect the up-scaling of laboratory and bench-scale research to
      field-scale application. It discusses the mechanisms of electrokinetic
      bioremediation in the subsurface environment at different micro and macroscales,
      the influence of environmental processes on electrokinetic phenomena and the
      design options available for application to the field scale. The review also
      presents results from a modelling exercise to illustrate the effectiveness of
      electrokinetics on the supply electron acceptors to a plume scale scenario where
      these are limiting. Current research needs include analysis of electrokinetic
      bioremediation in more representative environmental settings, such as those in
      physically heterogeneous systems in order to gain a greater understanding of the
      controlling mechanisms on both electrokinetics and bioremediation in those
      scenarios. 

PMID- 24875869
TI  - Influence and interactions of multi-factors on the bioavailability of PAHs in
      compost amended contaminated soils.
AB  - Compost amendment to contaminated soils is a potential approach for waste
      recycling and soil remediation. The relative importance and interactions of
      multiple factors on PAH bioavailability in soils were investigated using conjoint
      analysis and five-way analysis of variance. Results indicated that soil type and
      contact time were the two most significant factors influencing the PAH
      bioavailability in amended soils. The other two factors (compost type and ratio
      of compost addition) were less important but their interactions with other
      factors were significant. Specifically the 4-factor interactions showed that
      compost addition stimulated the degradation of high molecular PAHs at the initial
      stage (3 month) by enhancing the competitive sorption within PAH groups. Such
      findings suggest that a realistic decision-making towards hydrocarbon
      bioavailability assessment should consider interactions among various factors.
      Further to this, this study demonstrated that compost amendment can enhance the
      removal of recalcitrant hydrocarbons such as PAHs in contaminated soils.

PMID- 24875870
TI  - Characterization of carbohydrates in rainwater from the southeastern North
      Carolina.
AB  - Carbohydrates have been widely reported in atmospheric aerosols, but have not
      previously been quantified in rainwater. We have identified and quantified a
      series of 11 specific compounds including monosaccharides (glucose, fructose,
      arabinose, galactose and pinitol), disaccharides (sucrose and trehalose), sugar
      alcohols (arabitol, dulcitol and mannitol) and the anhydrosaccharide
      levoglucosan. Rainwater analyzed in this study includes 52 distinct precipitation
      events in Wilmington, NC between June 2011 and October 2012. Our analysis
      indicates carbohydrates typically contribute <1% of total dissolved organic
      carbon in rain, but can account for as much as 10-35% during periods of high
      pollen or local fires. Concentrations of individual carbohydrates reached as high
      as 5.8 MUM, with glucose and sucrose typically being the predominant species. The
      distribution of carbohydrates exhibited a distinct seasonal pattern, with higher
      concentrations of most carbohydrates, especially sucrose, in spring and summer,
      driven primarily by increased biogenic inputs during the growing season.
      Concentrations of carbohydrates were an order of magnitude higher in storms of
      terrestrial origin compared to marine events, further supporting a terrestrial
      biogenic origin of most species. Sequential sampling of Hurricane Irene showed
      significant quantities of carbohydrates present at the end of the storm when air
      mass back trajectories traversed over land. The highest level of levoglucosan, a
      compound associated with biomass burning, was detected in rain with an air mass
      back trajectory that traveled over a region affected by wildfires. When compared
      to aerosol concentrations reported by others, the sugar concentrations in rain
      demonstrate wet deposition is an important removal mechanism of this water
      soluble and bioavailable fraction of atmospheric particulate organic matter.

PMID- 24875871
TI  - Surfactant-modified fatty acid composition of Citrobacter sp. SA01 and its effect
      on phenanthrene transmembrane transport.
AB  - The effects of the surfactants, Tween 80 and sodium dodecyl benzene sulfonate
      (SDBS) on a membrane's fatty acid composition and the transmembrane transport of
      phenanthrene were investigated. The results indicated that both surfactants could
      modify the composition of fatty acids of Citrobacter sp. Strain SA01 cells, 50 mg
      L(-1) of both surfactants changed the composition of the fatty acids the most,
      increasing the amount of unsaturated fatty acids. The comparison of fatty acid
      profiles with diphenylhexatriene fluorescence anisotropy, a probe for plasma
      membrane fluidity, suggested that an increased amount of unsaturated fatty acids
      corresponded to greater membrane fluidity. In addition, increased unsaturated
      fatty acids promoted phenanthrene to partition from the extracellular matrix to
      cell debris, which increased reverse partitioning from the cell debris to the
      cytochylema. The results of this study were expected in that the addition of a
      surfactant is a simple and effective method for accelerating the rate-limiting
      step of transmembrane transport of hydrophobic organic compounds (HOCs) in
      bioremediation.

PMID- 24875872
TI  - Identification of phase II pharmaceutical metabolites in reclaimed water using
      high resolution benchtop Orbitrap mass spectrometry.
AB  - This study described an analytical method for the identification of common phase
      II pharmaceutical metabolites in reclaimed water using liquid chromatography high
      resolution Orbitrap mass spectrometry after solid phase extraction (SPE).
      Orbitrap mass spectrometer was operated at resolution of 70000 in MS mode and
      35000 in data-dependent MS/MS mode, without using lock mass. Firstly, parent
      drugs and their metabolites were tentatively identified based on accurate mass
      using a mass tolerance of 5 ppm. A detailed examination of the extracted ion
      chromatograms (XICs) for all potential metabolites revealed the presence of two
      phase II metabolites of sulfamethoxazole, acetylsulfamethoxazole and
      sulfamethoxazole glucuronide in reclaimed water. Secondly, the high resolution
      data-dependent MS/MS spectra of each compound were further investigated using
      metabolic profiling software. After comparing characteristic ions obtained in
      MS/MS mode with those predicted by the software and reported in previous studies,
      the two phase II metabolites were positively identified in reclaimed water.
      Lastly, the two metabolites were detected and quantified in the reclaimed water
      samples collected during a period of one month. As a result, averaged
      concentrations of sulfamethoxazole, acetylsulfamethoxazole and sulfamethoxazole
      glucuronide were calculated at 2848 +/- 1367 ng L(-)(1), 1980 +/- 1410 ng L(
      )(1), and 2859 +/- 1526 ng L(-)(1), respectively. The two metabolites represented
      54% of the source of sulfamethoxazole in reclaimed water suggesting the
      importance of measuring pharmaceutical metabolites in the environment. To our
      knowledge, this is the first known report of sulfamethoxazole glucuronide
      surviving intact through wastewater treatment plants and occurring in
      environmental water samples.

PMID- 24875873
TI  - Evaluation of the QuEChERS method for the extraction of pharmaceuticals and
      personal care products from drinking-water treatment sludge with determination by
      UPLC-ESI-MS/MS.
AB  - A modified version of the QuEChERS method has been evaluated for the
      determination of 21 pharmaceuticals and 6 personal care products (PPCPs) in
      drinking-water sludge samples by employing ultra high liquid chromatography
      tandem mass spectrometry (UPLC-MS/MS). The performance of the method was
      evaluated through linearity, recovery, precision (intra-day), method detection
      and quantification limits (MDL and MQL) and matrix effect. The calibration curves
      prepared in acetonitrile and in the matrix extract showed a correlation
      coefficient ranging from 0.98 to 0.99. MQLs values were on the ng g(-1) order of
      magnitude for most compounds. Recoveries between 50% and 93% were reached with
      RSDs lower than 10% for most compounds. Matrix effect was almost absent with
      values lower than 16% for 93% of the compounds. By coupling a quick and simple
      extraction called QuEChERS with the UPLC-MS/MS analysis, a method that is both
      selective and sensitive was obtained. This methodology was successfully applied
      to real samples and caffeine and benzophenone-3 were detected in ng g(-1) levels.

PMID- 24875874
TI  - A review on black carbon emissions, worldwide and in China.
AB  - Black carbon (BC) produced from open burning (OB) and controlled combustion (CC)
      is a range of carbonaceous products of incomplete combustion of biomass and
      fossil fuel, and is deemed as one of the major contributors to impact global
      environment and human health. BC has a strong relationship with POPs, in waste
      combustion, BC promotes the formation of POPs, and then the transport of POPs in
      the environment is highly influenced by BC. However less is known about BC
      formation, measurement and emissions estimation especially in developing
      countries such as China. Different forms of BC are produced both in CC and OB. BC
      emission characteristics and combustion parameters which determine BC emissions
      from CC and OB are discussed. Recent studies showed a lack of common methodology
      and the resulting data for describing the mechanisms related to BC formation
      during combustion processes. Because BC is a continuum carbonaceous combustion
      product, different sampling and measuring methods are used for measuring their
      emissions with great quantitative uncertainty. We discuss the commonly used BC
      sampling and measuring methods along with the causes for uncertainty and measures
      to minimizing the uncertainty. Then, we discuss the estimations of BC emission
      factors and emission inventory for CC and OB sources. The total emissions of BC
      from CC and OB in China are also estimated and compared with previous BC emission
      inventories in this review and we find the inventories tend to be overestimated.
      As China becomes the largest contributor to global BC emissions, studies for
      characterizing BC emissions from OB and CC sources are absent in China. Finally,
      we comment on the current state of BC emission research and identify major
      deficiencies that need to overcome. Moreover, the advancement in research tools,
      measuring technique in particular, as discussed in this review is critical for
      researchers in developing countries to improve their capability to study BC
      emissions for addressing the growing climate change and public health concerns. 

PMID- 24875875
TI  - Carbon and chlorine isotope fractionation during Fenton-like degradation of
      trichloroethene.
AB  - Dual isotope approach has been proposed as a viable tool for characterizing and
      assessing in situ contaminant transformation, however, little data is currently
      available on its applicability to chlorinated ethenes. This study determined
      carbon and chlorine isotope fractionation during Fenton-like degradation of
      trichloroethene (TCE). Carbon and chlorine isotope enrichment factors were
      epsilonC=-2.9 +/- 0.30/00 and epsilonCl=-0.9 +/- 0.10/00, respectively. An
      observed small secondary chlorine isotope effect (AKIECl=1.001) was consistent
      with an initial transformation by adding hydroxyl radicals (OH) to CC bonds
      without cleavage of CCl bonds. The relative change in carbon and chlorine isotope
      ratios (Delta=Deltadelta(13)C/Deltadelta(37)Cl) was calculated to be 3.1 +/- 0.2,
      approximately equal to the ratio of chlorine and carbon isotope enrichment
      factors (epsilonC/epsilonCl=3.2). The similarity of the Delta (or
      epsilonC/epsilonCl) values between Fenton-like degradation and microbial
      reductive dechlorination of TCE was observed, indicating that application of
      solely dual isotope approach may be limited in distinguishing the two
      transformation pathways.

PMID- 24875876
TI  - Efficiency of soil organic and inorganic amendments on the remediation of a
      contaminated mine soil: II. Biological and ecotoxicological evaluation.
AB  - The feasibility of two organic materials (pig slurry and compost) in combination
      with hydrated lime for the remediation of a highly acidic trace elements (TEs)
      contaminated mine soil was assessed in a mesocosm experiment. The effects of the
      amendments on soil biochemical and ecotoxicological properties were evaluated and
      related with the main physicochemical characteristics of soil and soil solution.
      The original soil showed impaired basic ecological functions due to the high
      availability of TEs, its acidic pH and high salinity. The three amendments
      slightly reduced the direct and indirect soil toxicity to plants, invertebrates
      and microorganisms as a consequence of the TEs' mobility decrease in topsoil,
      reducing therefore the soil associated risks. The organic amendments, especially
      compost, thanks to the supply of essential nutrients, were able to improve soil
      health, as they stimulated plant growth and significantly increased enzyme
      activities related with the key nutrients in soil. Therefore, the use of compost
      or pig slurry, in combination with hydrated lime, decreased soil ecotoxicity and
      seems to be a suitable management strategy for the remediation of highly acidic
      TEs contaminated soils. 

PMID- 24875877
TI  - Effects of biochar and the geophagous earthworm Metaphire guillelmi on fate of
      (14)C-catechol in an agricultural soil.
AB  - Both biochar and earthworms can exert influence on behaviors of soil-borne
      monomeric phenols in soil; however, little was known about the combined effects
      of biochar and earthworm activities on fate of these chemicals in soil. Using
      (14)C-catechol as a representative, the mineralization, transformation and
      residue distribution of phenolic humus monomer in soil amended with different
      amounts of biochar (0%, 0.05%, 0.5%, and 5%) without/with the geophagous
      earthworm Metaphire guillelmi were investigated. The results showed biochar at
      amendment rate <0.5% did not affect (14)C-catechol mineralization, whereas 5%
      biochar amendment significantly inhibited the mineralization. Earthworms did not
      affect the mineralization of (14)C-catechol in soil amended with <0.5% biochar,
      but significantly enhanced the mineralization in 5% biochar amended soil when
      they were present in soil for 9 d. When earthworms were removed from the soil,
      the mineralization of (14)C-catechol was significantly lower than that of in
      earthworm-free soil indicating that (14)C-catecholic residues were stabilized
      during their passage through earthworm gut. The assimilation of (14)C by
      earthworms was low (1.2%), and was significantly enhanced by biochar amendment,
      which was attributed to the release of biochar-associated (14)C-catecholic
      residues during gut passage of earthworm. 

PMID- 24875878
TI  - Revealing organic carbon-nitrate linear relationship from UV spectra of
      freshwaters in agricultural environment.
AB  - A strong non linear relationship between nitrate and organic matter (assessed by
      dissolved organic carbon, DOC) has been recently demonstrated by Taylor and
      Townsend (2010), namely for freshwaters. In this context, our study explores this
      relation from the behavior of sets of normalized UV spectra (same area under each
      spectrum) of different water samples showing a hidden isosbestic point (HIP)
      around 225 nm. This HIP is linked to the existence of a simple relation between
      nitrate and DOC, the proportions of which vary according to the sampling location
      and environmental factors. In a second step, a simple linear model is proposed
      for nitrate-DOC relationship (alpha?NO3+beta?DOC=1) and a validation is proposed
      for more than 150 samples of different Brittany rivers and lakes. For samples of
      the largest watershed, a complementary exploitation from data acquired during the
      different campaigns confirmed the seasonal evolution between spring (high
      nitrate/low DOC) and autumn (high DOC/low nitrate). Further investigation on
      other freshwater samples is needed in order to improve the limits of this linear
      model.

PMID- 24875880
TI  - Biogenic and anthropogenic organic components of Saharan sands.
AB  - Till now, the Sahara desert sands have scarcely characterized for their organic
      contents, despite they are known to heavily affect Europe and America when
      transported by winds. In this study, the composition of sands collected in ten
      oasis lying in two regions of the Algerian Sahara during 2011 was investigated
      with regards to organic fraction. Attention was paid to anthropogenic and
      biogenic sources of organics associated to sands, through the characterization of
      n-alkanes, n-alkanoic and n-alkanedioic acids, n-alkanols, sterols, PAHs and
      caffeine. The organic fraction load on sands associable to natural sources was
      higher in the Region of Biskra than in that of Ouargla. The biogenic contribution
      to the total amount of organics in sands exceeded that of the anthropogenic
      sources. The composition of sands from Hassi Messaoud, compared to that observed
      there in 2006, showed that the anthropic impact over the region was not changed. 

PMID- 24875879
TI  - Efficiency of soil organic and inorganic amendments on the remediation of a
      contaminated mine soil: I. Effects on trace elements and nutrients solubility and
      leaching risk.
AB  - A mesocosm experiment, in columns, was conducted in a growth chamber to assess
      the viability of two organic materials (pig slurry and compost; in combination
      with hydrated lime) for the remediation of a highly acidic and trace elements
      (TEs) contaminated mine soil and the reduction of its associated leaching risks.
      Their influence on the evolution throughout the soil depth of the physicochemical
      properties (including TEs mobility) of the soil and soil solution (in situ
      periodic collection) and on Lolium perenne growth and foliar TEs accumulation was
      evaluated. Soluble and extractable concentrations of the different TEs were
      considerably high, although the organic amendments (with lime) and lime addition
      successfully decreased TEs mobility in the top soil layer, as a consequence of a
      rise in pH and changes in the redox conditions. Compost and pig slurry increased
      the soluble organic-C and dissolved N, K and P of the soil, producing a certain
      downwards displacement of N and K. The organic amendments allowed the growth of
      L. perenne in the soil, thus indicating improvement of soil conditions, but
      elevated TEs availability in the soil led to toxicity symptoms and abnormally
      high TEs concentrations in the plants. An evaluation of the functioning and
      ecotoxicological risks of the remediated soils is reported in part II: this
      allows verification of the viability of the amendments for remediation
      strategies. 

PMID- 24875881
TI  - Enhancement of the photocatalytic activity of Ferrous Oxide by doping onto the
      nano-clinoptilolite particles towards photodegradation of tetracycline.
AB  - Photodegradation of tetracycline (TC) aqueous solution by FeO doped onto nano
      clinoptilolite particles was investigated using a high pressure Hg lamp as
      radiation source. Nano-particles of clinoptilolite were prepared using ball
      milling of micro crystals of zeolite. The pretreated nano-particles ion exchanged
      in a ferrous solution and the Fe(II)-exchanged form was calcined at 450 degrees
      C. All samples were characterized by FT-IR, DRS, SEM and XRD. The degradation
      extent was determined via UV-Vis absorption spectroscopy and COD. Based on the
      study of the effect of key operating parameters, the optimal conditions were
      determined to reach the higher efficiency of the process. The best photocatalytic
      activity was obtained in presence of the catalyst containing 5.4% FeO. 

PMID- 24875882
TI  - Rapid evolution of PARP genes suggests a broad role for ADP-ribosylation in host
      virus conflicts.
AB  - Post-translational protein modifications such as phosphorylation and
      ubiquitinylation are common molecular targets of conflict between viruses and
      their hosts. However, the role of other post-translational modifications, such as
      ADP-ribosylation, in host-virus interactions is less well characterized. ADP
      ribosylation is carried out by proteins encoded by the PARP (also called ARTD)
      gene family. The majority of the 17 human PARP genes are poorly characterized.
      However, one PARP protein, PARP13/ZAP, has broad antiviral activity and has
      evolved under positive (diversifying) selection in primates. Such evolution is
      typical of domains that are locked in antagonistic 'arms races' with viral
      factors. To identify additional PARP genes that may be involved in host-virus
      interactions, we performed evolutionary analyses on all primate PARP genes to
      search for signatures of rapid evolution. Contrary to expectations that most PARP
      genes are involved in 'housekeeping' functions, we found that nearly one-third of
      PARP genes are evolving under strong recurrent positive selection. We identified
      a >300 amino acid disordered region of PARP4, a component of cytoplasmic vault
      structures, to be rapidly evolving in several mammalian lineages, suggesting this
      region serves as an important host-pathogen specificity interface. We also found
      positive selection of PARP9, 14 and 15, the only three human genes that contain
      both PARP domains and macrodomains. Macrodomains uniquely recognize, and in some
      cases can reverse, protein mono-ADP-ribosylation, and we observed strong
      signatures of recurrent positive selection throughout the macro-PARP
      macrodomains. Furthermore, PARP14 and PARP15 have undergone repeated rounds of
      gene birth and loss during vertebrate evolution, consistent with recurrent gene
      innovation. Together with previous studies that implicated several PARPs in
      immunity, as well as those that demonstrated a role for virally encoded
      macrodomains in host immune evasion, our evolutionary analyses suggest that
      addition, recognition and removal of ADP-ribosylation is a critical,
      underappreciated currency in host-virus conflicts.

PMID- 24875884
TI  - BRG1 expression is increased in thoracic aortic aneurysms and regulates
      proliferation and apoptosis of vascular smooth muscle cells through the long non
      coding RNA HIF1A-AS1 in vitro.
AB  - OBJECTIVES: Brahma-related gene 1 (BRG1) and long non-coding RNAs (lncRNAs) play
      important roles in cellular processes. However, little is known regarding their
      roles in thoracic aortic aneurysms. We investigated BRG1 expression in thoracic
      aortic aneurysms and the roles of BRG1 and the lncRNA HIF 1 alpha-antisense RNA 1
      in regulating the proliferation and apoptosis of aortic smooth muscle cells in
      vitro. METHODS: BRG1 mRNA and protein expression in human aortic media specimens
      were examined by quantitative real-time polymerase chain reaction,
      immunohistochemical staining and western blot. BRG1 expression was up-regulated
      by lentiviral vectors. Vascular smooth muscle cell proliferation and apoptosis
      were studied using Cell Counting Kit-8 and terminal deoxynucleotidyl transferase
      dUTP nick-end labelling assays. We performed western blots to detect Caspase3 and
      Bcl2 protein expression. LncRNAs regulated by BRG1 were identified through
      microarray in BRG1 gain- and loss-of-function vascular smooth muscle cells.
      Finally, the expression of HIF 1 alpha-antisense RNA 1 was reduced by siRNA and
      cell proliferation and apoptosis was studied using Cell Counting Kit-8 assays,
      caspase-3 activity assays and western blot. RESULTS: BRG1 expression in the
      aortic media was significantly higher in thoracic aortic aneurysms than in normal
      controls. Overexpression of BRG1 in human aortic smooth muscle cells promoted
      apoptosis and reduced proliferation. The expression of HIF 1 alpha-antisense RNA
      1 was significantly down- and up-regulated in BRG1 knock-down and overexpressing
      vascular smooth muscle cells, respectively. We further demonstrated that
      suppression of HIF 1 alpha-antisense RNA 1 by siRNA in vascular smooth muscle
      cells reduced apoptosis and promoted proliferation. CONCLUSIONS: BRG1 is
      overexpressed in the aortic media of thoracic aortic aneurysms and the
      interaction between BRG1 and HIF 1 alpha-antisense RNA 1 plays a key role in the
      proliferation and apoptosis of vascular smooth muscle cells in vitro, which may
      contribute to the pathogenesis of thoracic aortic aneurysms.

PMID- 24875885
TI  - Is the lymphatic drainage of lung cancer lobe-specific? A surgical appraisal.
AB  - OBJECTIVES: Nowadays, early-stage lung cancers are more frequently encountered.
      Selective lymph node (LN) dissection based on lobe-specific lymphatic pathway has
      been proposed. Our aim was to study nodal involvement according to tumour
      location. METHODS: We reviewed 1779 lobectomized patients and analysed their
      pathological characteristics according to tumour location: Group 1 (G1), right
      upper lobe; Group 2 (G2), right middle lobe; Group 3 (G3), right lower lobe;
      Group 4 (G4), left upper division; Group 5 (G5), lingula; Group 6 (G6), left
      lower lobe. The pN status was recorded for each group to analyse the lymphatic
      spread of non-small-cell lung cancer (NSCLC) according to tumour location.
      RESULTS: The numbers and proportions of lobectomies in each group were 613
      patients in G1 (59.2%), 64 in G2 (6.4%), 359 in G3 (34.6%), 404 in G4 (54.3%), 54
      in G5 (7.3%) and 286 in G6 (38.4%). The rates of pN2 involvement were similar,
      whatever the group was, even when deciphering single- and multistation diseases.
      on the right side, single-station N2 disease was mainly found in the superior
      mediastinum (SM) for G1 (95%), and in the inferior for G3 (90%). On the left
      side, single-station N2 was mainly found in the SM in G4 (94%), and the inferior
      in G6 (48%). Whatever the side, in case of two-station involvement, both
      mediastina were concerned in 40% (in G4) to 81% of the case (in G3). Long-term
      survival rates were different in skip metastasis, single- and multistation
      involvement, but not between lobes. CONCLUSIONS: Tumour location is not a
      predictor of nodal metastasis pattern. In surgical treatment of NSCLC, complete
      systematic mediastinal LN dissection remains the only acceptable procedure from
      an oncological point of view.

PMID- 24875883
TI  - Bacterial superantigens promote acute nasopharyngeal infection by Streptococcus
      pyogenes in a human MHC Class II-dependent manner.
AB  - Establishing the genetic determinants of niche adaptation by microbial pathogens
      to specific hosts is important for the management and control of infectious
      disease. Streptococcus pyogenes is a globally prominent human-specific bacterial
      pathogen that secretes superantigens (SAgs) as 'trademark' virulence factors.
      SAgs function to force the activation of T lymphocytes through direct binding to
      lateral surfaces of T cell receptors and class II major histocompatibility
      complex (MHC-II) molecules. S. pyogenes invariably encodes multiple SAgs, often
      within putative mobile genetic elements, and although SAgs are documented
      virulence factors for diseases such as scarlet fever and the streptococcal toxic
      shock syndrome (STSS), how these exotoxins contribute to the fitness and
      evolution of S. pyogenes is unknown. Here we show that acute infection in the
      nasopharynx is dependent upon both bacterial SAgs and host MHC-II molecules. S.
      pyogenes was rapidly cleared from the nasal cavity of wild-type C57BL/6 (B6)
      mice, whereas infection was enhanced up to ~10,000-fold in B6 mice that express
      human MHC-II. This phenotype required the SpeA superantigen, and vaccination with
      an MHC -II binding mutant toxoid of SpeA dramatically inhibited infection. Our
      findings indicate that streptococcal SAgs are critical for the establishment of
      nasopharyngeal infection, thus providing an explanation as to why S. pyogenes
      produces these potent toxins. This work also highlights that SAg redundancy
      exists to avoid host anti-SAg humoral immune responses and to potentially
      overcome host MHC-II polymorphisms. 

PMID- 24875887
TI  - GlideScope stylet associated with endotracheal tube T-connector split causing a
      breathing circuit leak.

PMID- 24875888
TI  - Broken spinal needle: case report and review of the literature.
AB  - The occurrence of broken spinal and epidural needles has been reported. However,
      most case reports have focused primarily on prevention rather than on management.
      A broken spinal needle fragment was left in a patient before it was removed one
      month later due to back pain. 

PMID- 24875889
TI  - Percussion pacing as management of nonresponsive asystole during pediatric
      strabismus surgery.

PMID- 24875890
TI  - Intranasal dexmedetomidine premedication reduces the minimum alveolar
      concentration of sevoflurane for tracheal intubation in children: a randomized
      trial.
AB  - STUDY OBJECTIVE: To determine the effects of dexmedetomidine premedication on the
      minimum alveolar concentration of sevoflurane for tracheal intubation (MACTI) in
      children. DESIGN: Prospective, randomized, clinical comparison study. SETTING:
      Operating room of an academic hospital. PATIENTS: 90 pediatric, ASA physical
      status 1 patients, aged 3 to 7 years, scheduled for minor elective surgery.
      INTERVENTIONS: Patients were randomized to three groups to receive placebo,
      dexmedetomidine 1 MUg/kg, or dexmedetomidine 2 MUg/kg approximately 60 minutes
      before anesthesia. Anesthesia was induced with sevoflurane. Each concentration of
      sevoflurane for which a tracheal intubation was attempted was predetermined
      according to modification of the Dixon's up-and-down method, with 0.25% as a step
      size and held constant for at least 15 minutes before tracheal intubation. All
      responses ("movement" or "no movement") to tracheal intubation were assessed.
      MEASUREMENTS AND MAIN RESULTS: The MACTI of sevoflurane was 2.82% +/- 0.17% in
      the control group, 2.26% +/- 0.18% in the 1 MUg/kg dexmedetomidine group, and
      1.83% +/- 0.16% in the 2 MUg/kg dexmedetomidine group. Dexmedetomidine
      premedication (1 and 2 MUg/kg) decreased the MACTI of sevoflurane by 20% and 35%,
      respectively. There were no clinically significant episodes of hypotension or
      bradycardia in any patients. CONCLUSION: Intranasal dexmedetomidine premedication
      produces a dose-dependent decrease in the concentration of sevoflurane needed for
      tracheal intubation in children.

PMID- 24875891
TI  - An unusual cause of cerebellar and oculomotor dysfunction by rapid infusion of
      meperidine.

PMID- 24875893
TI  - Truncated trigonal prismatic tubular crystals consisting of a zeolite L-mimic
      metal-organic framework.
AB  - Research on the construction, crystal morphology, and functions of a novel
      zeolite L-mimic metal-organic framework (ZLMOF) was carried out. Treatment of the
      tubular crystals with AgBF4 in acetone at 40  degrees C smoothly coated the
      surface of the ZLMOF crystals with silver(0) nanoparticles. 

PMID- 24875892
TI  - Formation of a fibrin net on the polypropylene membrane oxygenator used for
      percutaneous cardiopulmonary support in a patient with acute myocarditis.

PMID- 24875894
TI  - A practical guide to self-sustaining point-of-care ultrasound education programs
      in resource-limited settings.
AB  - The value of point-of-care ultrasound education in resource-limited settings is
      increasingly recognized, though little guidance exists on how to best construct a
      sustainable training program. Herein we offer a practical overview of core
      factors to consider when developing and implementing a point-of-care ultrasound
      education program in a resource-limited setting. Considerations include analysis
      of needs assessment findings, development of locally relevant curriculum, access
      to ultrasound machines and related technological and financial resources, quality
      assurance and follow-up plans, strategic partnerships, and outcomes measures.
      Well-planned education programs in these settings increase the potential for long
      term influence on clinician skills and patient care. 

PMID- 24875895
TI  - What is the best first-line agent for benzodiazepine-resistant convulsive status
      epilepticus?

PMID- 24875896
TI  - Patient flow in the emergency department: a classification and analysis of
      admission process policies.
AB  - STUDY OBJECTIVE: We investigate the effect of admission process policies on
      patient flow in the emergency department (ED). METHODS: We surveyed an advisory
      panel group to determine approaches to admission process policies and classified
      them as admission decision is made by the team of providers (attending
      physicians, residents, physician extenders) (type 1) or attending physicians
      (type 2) on the admitting service, team of providers (type 3), or attending
      physicians (type 4) in the ED. We developed discrete-event simulation models of
      patient flow to evaluate the potential effect of the 4 basic policy types and 2
      hybrid types, referred to as triage attending physician consultation and remote
      collaborative consultation on key performance measures. RESULTS: Compared with
      the current admission process policy (type 1), the alternatives were all
      effective in reducing the length of stay of admitted patients by 14% to 26%. In
      other words, patients may spend 1.4 to 2.5 hours fewer on average in the ED
      before being admitted to internal medicine under a new admission process policy.
      The improved flow of admitted patients decreased both the ED length of stay of
      discharged patients and the overall length of stay by up to 5% and 6.4%,
      respectively. These results are framed in context of teaching mission and
      physician experience. CONCLUSION: An efficient admission process can reduce
      waiting times for both admitted and discharged ED patients. This study
      contributed to demonstrating the potential value of leveraging admission process
      policies and developing a framework for pursuing these policies.

PMID- 24875897
TI  - Expression and localization of 20alpha-hydroxysteroid dehydrogenase (20alpha-HSD)
      in porcine reproductive tissues during pregnancy.
AB  - The aims of this study were to determine the specific site of 20alpha-HSD
      expression in the reproductive tissues on day 30 of pregnancy and during pre
      parturition. 20alpha-HSD mRNA was demonstrated to have the highest expression in
      the placenta on day 30 of pregnancy and in the ovary during pre-parturition. Weak
      mRNA expression was observed in the uterus and ovary on day 30 of pregnancy.
      However, the mRNA was not expressed in the oviduct on day 30 of pregnancy. The
      mRNA was also specifically detected in the placenta on day 30 of pregnancy by
      northern blot analysis. Western blot analysis indicated that the expression
      pattern of the 20alpha-HSD protein in the reproductive tissues was similar to
      that of 20alpha-HSD mRNA. Immunohistochemical analysis also revealed that the pig
      20alpha-HSD protein was localized in the trophoblast villus in the placenta on
      day 30 of pregnancy. It was highly expressed in the glandular epithelial cells of
      the endometrium and the luminal epithelial cells of the uterus. The 20alpha-HSD
      protein was highly localized in the large luteal cells of the ovary on day 30 of
      pregnancy and during pre-parturition. Taken together, our study demonstrated that
      the pig 20alpha-HSD mRNA and protein are mainly localized in the trophoblast
      villus in the placenta on day 30 of pregnancy. The expression of the protein is
      also localized in the large luteal cells of the ovary. In addition, the protein
      is highly expressed in the glandular epithelial cells of the endometrium and the
      luminal epithelial cells of the uterus.

PMID- 24875899
TI  - Cross-scale interactions and the distribution-abundance relationship.
AB  - Positive interspecific relationships between local abundance and extent of
      regional distribution are among the most ubiquitous patterns in ecology. Although
      multiple hypotheses have been proposed, the mechanisms underlying distribution
      abundance (d-a) relationships remain poorly understood. We examined the intra-
      and interspecific distribution-abundance relationships for a metacommunity of 13
      amphibian species sampled for 15 consecutive years. Mean density of larvae in
      occupied ponds was positively related to number of ponds occupied by species;
      employing the fraction of ponds uniquely available to each species this same
      relationship sharply decelerates. The latter relationship suggested that more
      abundant species inhabited most available habitats annually, whereas rarer
      species were dispersal limited. We inferred the mechanisms responsible for this
      pattern based on the dynamics of one species, Pseudacris triseriata, which
      transitioned between a rare, narrowly distributed species to a common, widely
      distributed species and then back again. Both transitions were presaged by marked
      changes in mean local densities driven by climatic effects on habitat quality. We
      identified threshold densities separating these population regime shifts that
      differed with landscape configuration. Our data suggest that these transitions
      were caused by strong cross-scale interactions between local resource/niche
      processes and larger scale metapopulation processes. The patterns we observed
      have relevance for understanding the mechanisms of interspecific d-a
      relationships and critical thresholds associated with habitat fragmentation. 

PMID- 24875900
TI  - Re: Fisher CG, Vaccaro AR, Prasad SK, et al. Evidence-based recommendations for
      spine surgery. Spine (Phila Pa 1976) 2014;39:E52-9.

PMID- 24875902
TI  - At the right distance: ER-mitochondria juxtaposition in cell life and death.
AB  - The interface between mitochondria and the endoplasmic reticulum is emerging as a
      crucial hub for calcium signalling, apoptosis, autophagy and lipid biosynthesis,
      with far reaching implications in cell life and death and in the regulation of
      mitochondrial and endoplasmic reticulum function. Here we review our current
      knowledge on the structural and functional aspects of this interorganellar
      juxtaposition. This article is part of a Special Issue entitled: Calcium
      Signaling In Health and Disease. Guest Editors: Geert Bultynck, Jacques Haiech,
      Claus W. Heizmann, Joachim Krebs, and Marc Moreau. 

PMID- 24875898
TI  - Mechanisms underlying the effects of prenatal psychosocial stress on child
      outcomes: beyond the HPA axis.
AB  - Accumulating evidence from preclinical and clinical studies indicates that
      maternal psychosocial stress and anxiety during pregnancy adversely affect child
      outcomes. However, knowledge on the possible mechanisms underlying these
      relations is limited. In the present paper, we review the most often proposed
      mechanism, namely that involving the HPA axis and cortisol, as well as other less
      well-studied but possibly relevant and complementary mechanisms. We present
      evidence for a role of the following mechanisms: compromised placental
      functioning, including the 11beta-HSD2 enzyme, increased catecholamines,
      compromised maternal immune system and intestinal microbiota, and altered health
      behaviors including eating, sleep, and exercise. The roles of (epi)genetics, the
      postnatal environment and the fetus are also discussed. We conclude that maternal
      prenatal psychosocial stress is a complex phenomenon that affects maternal
      emotions, behavior and physiology in many ways, and may influence the physiology
      and functioning of the fetus through a network of different pathways. The review
      concludes with recommendations for future research that helps our understanding
      of the mechanisms by which maternal prenatal stress exerts its effect on the
      fetus. 

PMID- 24875903
TI  - A mutation leading to super-assembly of twin-arginine translocase (Tat) protein
      complexes.
AB  - The Tat system transports folded proteins across the bacterial plasma membrane.
      The mechanism is believed to involve coalescence of a TatC-containing unit with a
      separate TatA complex, but the full translocation complex has never been
      visualised and the assembly process is poorly defined. We report the analysis of
      the Bacillus subtilis TatAyCy system, which occurs as separate TatAyCy and TatAy
      complexes at steady state, using single-particle electron microscopy (EM) and
      advanced atomic force microscopy (AFM) approaches. We show that a P2A mutation in
      the TatAy subunit leads to apparent super-assembly of Tat complexes. Purification
      of TatCy-containing complexes leads to a large increase in the TatA:TatC ratio,
      suggesting that TatAy(P2A) complexes may have attached to the TatAyCy complex. EM
      and AFM analyses show that the wild-type TatAyCy complex purifies as roughly
      spherical complexes of 9-16nm diameter, whereas the P2A mutation leads to
      accumulation of large (up to 500nm long) fibrils that are chains of numerous
      complexes. Time lapsed AFM imaging, recorded on fibrils under liquid, shows that
      they adopt a variety of tightly curved conformations, with radii of curvature of
      10-12nm comparable to the size of single TatAy(P2A) complexes. The combined data
      indicate that the mutation leads to super-assembly of TatAy(P2A) complexes and we
      propose that an individual TatAy(P2A) complex assembles initially with a
      TatAy(P2A)Cy complex, after which further TatAy(P2A) complexes attach to each
      other. The data further suggest that the N-terminal extracytoplasmic domain of
      TatAy plays an essential role in Tat complex interactions. 

PMID- 24875904
TI  - RANKL expression in myeloma cells is regulated by a network involving RANKL
      promoter methylation, DNMT1, microRNA and TNFalpha in the microenvironment.
AB  - We studied the regulation of RANKL expression in myeloma by promoter DNA
      methylation. Methylation-specific polymerase chain reaction showed complete
      methylation of RANKL promoter in WL-2 myeloma cells but partial methylation in
      eight other lines. 5-AzadC treatment of WL-2 cells led to demethylation and re
      expression of RANKL. Transwell and contact co-culture of WL-2 cells with normal
      bone marrow-derived mesenchymal stromal cells (BMSCs) resulted in comparable
      repression of DNA methyltransferase-1 (DNMT1) and re-expression of RANKL in WL-2
      cells. Moreover, treatment of WL-2 cells with TNFalpha led to repression of DNMT1
      and re-expression of RANKL in association with upregulation of miR-140-3p and miR
      126, which are partially offset by addition of anti-TNFalpha antibody to
      transwell-coculture of WL2 with BMSC. Taken together, our results showed that
      TNFalpha in the marrow microenvironment led to RANKL demethylation and re
      expression in myeloma cells through DNMT1 repression and upregulation of miR-126
      3p and miR-140, both known to repress DNMT1 translation. 

PMID- 24875905
TI  - Aquatic hazard and biodegradability of light and middle atmospheric distillate
      petroleum streams.
AB  - Light and middle atmospheric distillate petroleum substances are blended to
      produce fuels used in transportation and heating. These substances represent the
      majority by volume of crude oil refined products in the United States. The goal
      of this research was to develop biodegradability and aquatic toxicity data for
      four substances; heavy, straight-run naphtha (HSRN), hydro-desulfurized kerosene
      (HDK), hydro-cracked gas oil (HCGO), and catalytic-cracked gas oil (CCGO). Ready
      biodegradability tests demonstrated rapid and extensive microbial oxidation of
      these test substances, indicating a lack of persistence in the aquatic
      environment. Differences in biodegradation patterns reflected compositional
      differences in the constituent hydrocarbons. Results of aquatic toxicity tests on
      alga, cladocera, and fish demonstrated that toxicity was greatest for catalytic
      cracked gas oil, which contained a high proportion of aromatic hydrocarbons.
      Aromatic hydrocarbons are more soluble, and hence more bioavailable, resulting in
      higher toxicity. When expressed on the basis of loading rates, acute toxicity
      values (LL/EL50) ranged between 0.3 and 5.5 mg L(-1) for all three species, while
      chronic no-observed-effect loading rates (NOELR) ranged between 0.05 and 0.64 mg
      L(-1). PETROTOX estimates for acute and chronic toxicity ranged from 0.18 to 2.3
      mg L(-1) and 0.06 to 0.14 mg L(-1), respectively, which were generally more
      conservative than experimental data.

PMID- 24875906
TI  - A new in silico classification model for ready biodegradability, based on
      molecular fragments.
AB  - Regulations such as the European REACH (Registration, Evaluation, Authorization
      and restriction of Chemicals) often require chemicals to be evaluated for ready
      biodegradability, to assess the potential risk for environmental and human
      health. Because not all chemicals can be tested, there is an increasing demand
      for tools for quick and inexpensive biodegradability screening, such as computer
      based (in silico) theoretical models. We developed an in silico model starting
      from a dataset of 728 chemicals with ready biodegradability data (MITI-test
      Ministry of International Trade and Industry). We used the novel software SARpy
      to automatically extract, through a structural fragmentation process, a set of
      substructures statistically related to ready biodegradability. Then, we analysed
      these substructures in order to build some general rules. The model consists of a
      rule-set made up of the combination of the statistically relevant fragments and
      of the expert-based rules. The model gives good statistical performance with 92%,
      82% and 76% accuracy on the training, test and external set respectively. These
      results are comparable with other in silico models like BIOWIN developed by the
      United States Environmental Protection Agency (EPA); moreover this new model
      includes an easily understandable explanation. 

PMID- 24875907
TI  - Development of in silico models for predicting LSER molecular parameters and for
      acute toxicity prediction to fathead minnow (Pimephales promelas).
AB  - Many chemicals with toxic effects to aquatic species are produced every year. To
      date, linear solvation energy relationship (LSER) models for toxicity prediction
      to aquatic species are limited to non-polar and polar narcotic compounds. In this
      study, the Verhaar scheme was used to classify chemicals into five modes of toxic
      actions. LSER models for predicting acute toxicity to fathead minnow were
      developed by identifying chemical functional groups that influence toxicity
      prediction of reactive chemicals. Moreover, the predictive models that can be
      used to estimate LSER molecular parameters have been developed by using quantum
      chemical and Dragon descriptors. All the predictive models were developed
      following the OECD guidelines for QSAR model development and validation, with a
      satisfactory goodness-of-fit, robustness and predictive ability. The McGowans
      volume was the most significant descriptor in the toxicity models. This study
      also inferred that, compounds with carbonyl group have different behaviors such
      that some can biodegrade in the organism while others do not biodegrade, which
      might be the reason for the difficulties in modeling the acute toxicity of
      reactive chemicals. 

PMID- 24875908
TI  - Study on the interaction of catalase with pesticides by flow injection
      chemiluminescence and molecular docking.
AB  - The interaction mechanisms of catalase (CAT) with pesticides (including
      organophosphates: disulfoton, isofenphos-methyl, malathion, isocarbophos,
      dimethoate, dipterex, methamidophos and acephate; carbamates: carbaryl and
      methomyl; pyrethroids: fenvalerate and deltamethrin) were first investigated by
      flow injection (FI) chemiluminescence (CL) analysis and molecular docking. By
      homemade FI-CL model of lg[(I0-I)/I]=lgK+nlg[D], it was found that the binding
      processes of pesticides to CAT were spontaneous with the apparent binding
      constants K of 10(3)-10(5) L mol(-1) and the numbers of binding sites about 1.0.
      The binding abilities of pesticides to CAT followed the order:
      fenvalerate>deltamethrin>disulfoton>isofenphos
      methyl>carbaryl>malathion>isocarbophos>dimethoate>dipterex>acephate>methomyl>meth
      midophos, which was generally similar to the order of determination sensitivity
      of pesticides. The thermodynamic parameters revealed that CAT bound with
      hydrophobic pesticides by hydrophobic interaction force, and with hydrophilic
      pesticides by hydrogen bond and van der Waals force. The pesticides to CAT
      molecular docking study showed that pesticides could enter into the cavity
      locating among the four subdomains of CAT, giving the specific amino acid
      residues and hydrogen bonds involved in CAT-pesticides interaction. It was also
      found that the lgK values of pesticides to CAT increased regularly with
      increasing lgP, Mr, MR and MV, suggesting that the hydrophobicity and steric
      property of pesticide played essential roles in its binding to CAT.

PMID- 24875909
TI  - The effects of prenatal exposure to low-level cadmium, lead and selenium on birth
      outcomes.
AB  - To evaluate the current maternal and fetal exposure to cadmium (Cd), lead (Pb)
      and selenium (Se), and their potential effect on newborn birth outcomes, a cross
      sectional study involving an assessment of the levels of these three metals in
      maternal blood, urine and umbilical cord blood was conducted in 209 pregnant
      women living in Eastern China. The maternal blood, urine and cord blood samples
      were collected and measured with inductively coupled plasma mass spectrometry
      (ICP-MS). The maternal blood concentrations of Cd, Pb and Se (the geometric means
      (GMs) were 0.48, 39.50 and 143.53 MUg L(-1)) were significantly higher than and
      correlated with those in the cord blood (GM: 0.09, 31.62 and 124.61 MUg L(-1)).
      In the urine samples, the GMs for Cd, Pb and Se were 0.13, 0.48, and 4.78 MUg L(
      1), respectively. Passive smoking was found to positively correlate with urine Cd
      (r=0.16) and negatively correlate with urine Se (r=-0.29). The maternal blood Se
      level was negatively associated with the cord Cd levels (r=-0.41). The blood Cd
      concentration in the mother could significantly affect the newborn birth weight
      (r=-0.22), but it was not correlated with birth height. We identified cord Se as
      a new factor which significantly correlated with birth weight. In conclusion,
      maternal Cd, Pb, Se exposure correlated with their umbilical cord concentration,
      and maternal Cd exposure might affect the newborn birth weight. Increasing the Se
      intake might reduce the cord blood Cd concentration and promote the fetal growth.

PMID- 24875910
TI  - Association of CYP1A1, CYP1B1 and CYP17 gene polymorphisms and organochlorine
      pesticides with benign prostatic hyperplasia.
AB  - It is well established that steroidal hormones (testosterone and estrogen)
      increase benign prostatic hyperplasia (BPH) risk. Cytochrome P450 (CYP) enzymes
      especially CYP1A1, CYP1B1 and CYP17 metabolize these hormones. Apart from that,
      several endocrine disrupting organochlorine pesticides (OCPs) are reported to
      mimic the activity of these steroidal hormones. Therefore, functional
      polymorphisms in these genes and exposure to such pesticides may increase BPH
      risk further. Our study included 100 newly diagnosed BPH subjects and 100 age
      matched healthy male controls. CYP1A1, CYP1B1 and CYP17 polymorphisms were
      studied using PCR-RFLP and allele-specific PCR method. OCP levels in blood were
      analyzed by gas chromatography (GC). Levels of p,p'-DDE and endosulfan alpha were
      found to be significantly higher amongst BPH subjects as compared to controls (p
      values=0.001 and 0.03 respectively) and CYP17 polymorphism was observed to be
      significantly associated with BPH subjects as compared to controls (p
      values=0.03), indicating that these factors may be important risk factors for
      BPH. However, further studies are required before unequivocal conclusion. 

PMID- 24875911
TI  - Toxic effects of triazophos on rare minnow (Gobiocypris rarus) embryos and
      larvae.
AB  - Triazophos (TAP) has been widely used in agriculture for controlling insect pests
      and is a known organophosphorus pesticide. Due to TAP characteristics, such as
      high chemical and photochemical stability, its potential toxicity to aquatic
      organisms has gained great interest. To explore the potential developmental
      toxicity of TAP, Gobiocypris rarus embryos and larvae were exposed to various
      concentrations of TAP (0.1-15 mg L(-1)) until 72 h. Results showed that values of
      72 h LC50 and EC50 were 7.44 and 5.60 mg L(-1) for embryos, 2.52 and 1.37 mg L(
      1) for larvae. Increased malformation, decreased heart rate and body length
      provide a gradual concentration-dependent pattern. Enzyme activities and mRNA
      levels were significantly changed even at low concentration (0.05 mg L(-1) for
      embryos and 0.01 mg L(-(1) for larvae). Overall, the present study points out
      that TAP is likely a risk to the early development of G. rarus. The information
      presented in this study will be helpful in better understanding the toxicity
      induced by TAP in fish embryos and larvae.

PMID- 24875912
TI  - Use of toxicogenomics to predict the potential toxic effect of Benzo(a)pyrene on
      zebrafish embryos: ocular developmental toxicity.
AB  - Benzo(a)pyrene (BaP) is a representative polycyclic aromatic hydrocarbon (PAH),
      which is ubiquitous in the environment. The toxic effects of BaP on fish embryos
      have been described in detail, but some potentially toxic effects of BaP might
      have been neglected owing to the limitations of traditional techniques. In the
      present research, global transcriptional patterns were used to study the
      potentially toxic effects of BaP, as well as its underlying toxicological
      mechanisms. The expression levels of multiple genes were significantly changed by
      BaP exposure. The results of ontology assignments and cluster analysis showed
      that BaP could affect the processes of photoreceptor maintenance and
      phototransduction. We also conducted an experiment on phototactic response and
      found that larvae exposed to BaP displayed a decreasing response to light. In
      addition, BaP exposure decreased the cellular density of the ganglion cell layer
      (GCL) significantly. These results suggested that BaP exposure induced visual
      system developmental defects and dysfunction by perturbation of photoreceptor
      development related genes. Our results were helpful for an understanding of the
      toxicity of BaP. This study also indicated that microarray analysis was effective
      for predicting the potential toxicity of chemicals with high sensitivity and
      accuracy. 

PMID- 24875913
TI  - Elements levels in dogs from "triangle of death" and different areas of Campania
      region (Italy).
AB  - In the last twenty years, many concerns have raised in Campania region (Southern
      Italy) about illegal waste dumping and toxic waste and their possible adverse
      effects on health. Many human activities are considered to be important sources
      of environmental pollutants, elements among them. In this study, pet dogs were
      enrolled as environmental sentinels from three different areas of Campania, with
      a different degree of pollution, evaluating elements in blood and hair. The
      obtained data indicated that dogs from less polluted area were exposed to a hot
      spot of pollution, as only animals from one city (Sessa Aurunca) presented
      elements concentrations very close to toxic levels. When excluding these animals,
      the area proved to be the less contaminated. The present report confirm the
      higher degree of pollution of the most industrialized areas, and a certain
      concern originates from Cr, Ni and As, which are present as levels well above
      toxic thresholds. These data are indicative of a reduced pollution of the areas
      considered by Cd and Pb, but arise concern for Hg, As, Cr and Ni, which reach
      concentrations high enough to impact dogs and humans health, in term of acute (in
      the city of Sessa Aurunca) and chronic toxicity (i.e. reproduction impairment,
      endocrine disruption, immunosuppression). Additional studies are necessary to
      better define not only the precise distribution of hot spots of pollution, but
      also the real impact of such an exposure on the health of dogs, in term of
      endocrine balance and/or immune system activity. 

PMID- 24875914
TI  - Surfactants present complex joint effects on the toxicities of metal oxide
      nanoparticles.
AB  - The potential toxicities of nanoparticles (NPs) have been intensively discussed
      over the past decade. In addition to their single toxicities, NPs can interact
      with other environmental chemicals and thereby exert joint effects on biological
      systems and the environment. The present study investigated the combined
      toxicities of NPs and surfactants, which are among the chemicals that most likely
      coexist with NPs. Photobacterium phosphoreum was employed as the model organism.
      The results indicate that surfactants with different ion types can alter the
      properties of NPs (i.e., particle size and surface charge) in different ways and
      present complex joint effects on NP toxicities. Mixtures of different NPs and
      surfactants exhibited antagonistic, synergistic, and additive effects. In
      particular, the toxicity of ZnO was observed to result from its dissolved Zn(2+);
      thus, the joint effects of the ZnO NPs and surfactants can be explained by the
      interactions between the Zn ions and the surfactants. Our study suggests that the
      potential hazards caused by mixtures of NPs and surfactants are different from
      those caused by single NPs. Because surfactants are extensively used in the field
      of nanotechnology and are likely to coexist with NPs in natural waters, the
      ecological risk assessments of NPs should consider the impacts of surfactants. 

PMID- 24875916
TI  - Vertisol prevent cadmium accumulation in rice: analysis by ecophysiological
      toxicity markers.
AB  - Alfisol and vertisol cover more than fifty percent of rice fields in Asia. Rice
      cultivated in these soils is found to be contaminated with cadmium (Cd).
      Influence of physiochemical properties of these soils on Cd accumulation and
      ecophysiological functions of Oryza sativa L. cv MTU 7029 and MO 16 were
      analyzed. Plants grown in vertisol accumulated lower amount of Cd compare with
      those in alfisol. Soil properties such as cation exchange capacity and alkalinity
      played major role in decrease in Cd accumulation. Difference in Cd accumulation
      also reflected as more decrease in ecophysiological components such as biomass,
      relative water content and non-photochemical quenching among plants grown in
      alfisol. Plants grown in vertisol produced more flavanols, chlorophyll,
      anthocyanin, sugar, and protein than those in alfisol under Cd stress. But
      phenolic content was higher in plants grown in alfisol. Quantum efficiency of
      PSII, thiols, and silicon was increased while carotenes and calcium were
      decreased upon Cd accumulation. These changes were irrespective of soil type.
      Among the varieties chosen for the study, MTU 7029 accumulated more Cd compare
      with MO 16. It was concluded that soil properties caused difference in Cd
      accumulation among the plants grown in soils chosen and this would differentially
      reflect on specific ecophysiological markers. 

PMID- 24875915
TI  - Influence of releases of (129)I and (137)Cs from European reprocessing facilities
      in Fucus vesiculosus and seawater from the Kattegat and Skagerrak areas.
AB  - (129)I is a very long-lived radionuclide (T1/2=15.7*10(6) years) that is present
      in the environment because of natural and anthropogenic sources. Compared to the
      pre-nuclear era, large amounts of (129)I have been released to the marine
      environment, especially as liquid and gaseous discharges from two European
      reprocessing facilities located at Sellafield (England) and La Hague (France).
      The marine environment, i.e., the oceans, is the major source of iodine. Brown
      seaweed accumulates iodine at high levels up to 1.0% of dry weigh, and therefore
      they are ideal bioindicators for studying levels of (129)I. In this work, (129)I
      concentrations have been determined in seaweed Fucus vesiculosus and seawater
      collected in the Kattegat and Skagerrak areas in July 2007. The resulting data
      were evaluated in terms of (129)I concentrations and (129)I/(137)Cs ratios.
      (129)I concentrations were found to be in the order of (44-575)*10(9) atoms g(-1)
      in seaweed and (5.4-51)*10(9) atoms g(-1) in seawater, with an enhancement in the
      Skagerrak area in comparison to the Kattegat area. Iodine-129 concentrations in
      both seaweed and seawater were used to determine the concentration factor of
      iodine in brown seaweed F. vesiculosus. The high levels of (129)I and
      (129)I/(137)Cs ratios in the Skagerrak area and their gradually decreasing trend
      to the Kattegat indicates that the most important contribution to the (129)I
      inventory in those areas comes from Sellafield and La Hague reprocessing plants.

PMID- 24875917
TI  - Genotoxicity of mixtures of glyphosate and atrazine and their environmental
      transformation products before and after photoactivation.
AB  - The photo-inducible cytogenetic toxicity of glyphosate, atrazine, aminomethyl
      phosphoric acid (AMPA), desethyl-atrazine (DEA), and their various mixtures was
      assessed by the in vitro micronucleus assay on CHO-K1 cells. Results demonstrated
      that the cytogenetic potentials of pesticides greatly depended on their physico
      chemical environment. The mixture made with the four pesticides exhibited the
      most potent cytogenetic toxicity, which was 20-fold higher than those of the most
      active compound AMPA, and 100-fold increased after light-irradiation.
      Intracellular ROS assessment suggested the involvement of oxidative stress in the
      genotoxic impact of pesticides and pesticide mixtures. This study established
      that enhanced cytogenetic activities could be observed in pesticide mixtures
      containing glyphosate, atrazine, and their degradation products AMPA and DEA. It
      highlighted the importance of cocktail effects in environmental matrices, and
      pointed out the limits of usual testing strategies based on individual molecules,
      to efficiently estimate environmental risks. 

PMID- 24875918
TI  - Estrogenic activity of constituents of underarm deodorants determined by E-Screen
      assay.
AB  - The purpose of this study was to ascertain whether different kinds of underarm
      deodorants commercially available in Germany might contain substances with
      estrogenic potential which after use enter the aquatic environment via
      wastewater. Twenty five deodorants produced by ten different manufacturers in the
      form of sprays, roll-ons and sticks were investigated using an in vitro-test
      system (E-Screen assay) for the determination of estrogenic activity based on the
      human breast cancer cell line MCF-7. Seven out of ten spray deodorant samples
      showed a quantifiable estrogenic activity. In the case of the sticks and roll-ons
      it was only one out of six and one out of nine, respectively. The 17beta
      estradiol equivalent concentrations (EEQs) of the samples ranged from 0.1 ng g(
      1) to 9 ng g(-1) deodorant. Spray deodorant samples showed the highest activities
      in the E-Screen assay compared to the stick and roll-on deodorants. In order to
      identify substances possibly contributing to the observed biological activity the
      samples were additionally analyzed by GC/MS. The obtained results of this non
      target screening led to the selection of 62 single substances present in the
      deodorants which for their part were analyzed by E-Screen assay. Eight of these
      single substances, all of them fragrances, showed estrogenic effects with
      estradiol equivalence factors (EEFs) similar to parabens, a group of 4
      hydroxybenzoic acid esters commonly used as preservatives in personal care
      products, which are known to have a slight estrogenic effect. Thus, these
      fragrances are obviously responsible to a substantial degree for the observed
      estrogenic activity of the deodorants.

PMID- 24875919
TI  - Synthesis, characterization and toxicological evaluation of a core-shell copper
      oxide/polyaniline nanocomposite.
AB  - The newest generation of copper oxide NPs (CuO NPs) is the CuO core-shell (CS),
      which has potential applications in several areas (e.g., electronics and paint)
      and is able to provide a greater service life due to its coating; however, its
      toxicity is not fully understood. The objective of this study was to synthesize,
      characterize and evaluate the aquatic toxicology of CuO NPs and CuO core-shells
      through acute and chronic toxicity tests with the freshwater microcrustaceans
      Daphnia magna and to evaluate its acute toxicity with the marine bioluminescent
      bacteria Vibrio fischeri. The NPs were synthesized by direct thermal
      decomposition after being coated as a CS with polyaniline (PANI). With respect to
      acute toxicity with D. magna, the CuO NPs and CS CuO/PANI presented EC50 values
      of 0.32 mg L(-1) and 0.48 mg L(-1), respectively. For the tests with V. fischeri,
      the CuO NPs (EC50-15 min=7.79 mg L(-1)) exhibited behavior similar to that of the
      CS CuO/PANI (EC50-15 min=9.05 mg L(-1)) after 15 min of exposure. Regarding
      chronic toxicity, both forms showed a statistically significant effect (p<0.05)
      on the growth and reproduction parameters. Based on the characterization and
      toxicity results, it can be concluded that both forms of CuO were toxic and
      presented similar behaviors during the acute tests; however, after 21 d of
      exposure, CS CuO/PANI showed higher toxicity to the reproduction parameter,
      highlighting the importance of a complete study of the NP to better understand
      its toxicity mechanism.

PMID- 24875920
TI  - Matching pollution with adaptive changes in mangrove plants by multivariate
      statistics. A case study, Rhizophora mangle from four neotropical mangroves in
      Brazil.
AB  - Roots of mangrove trees have an important role in depurating water and sediments
      by retaining metals that may accumulate in different plant tissues, affecting
      physiological processes and anatomy. The present study aimed to evaluate adaptive
      changes in root of Rhizophora mangle in response to different levels of chemical
      elements (metals/metalloids) in interstitial water and sediments from four
      neotropical mangroves in Brazil. What sets this study apart from other studies is
      that we not only investigate adaptive modifications in R. mangle but also changes
      in environments where this plant grows, evaluating correspondence between
      physical, chemical and biological issues by a combined set of multivariate
      statistical methods (pattern recognition). Thus, we looked to match changes in
      the environment with adaptations in plants. Multivariate statistics highlighted
      that the lignified periderm and the air gaps are directly related to the
      environmental contamination. Current results provide new evidences of root
      anatomical strategies to deal with contaminated environments. Multivariate
      statistics greatly contributes to extrapolate results from complex data matrixes
      obtained when analyzing environmental issues, pointing out parameters involved in
      environmental changes and also evidencing the adaptive response of the exposed
      biota. 

PMID- 24875921
TI  - Children's personal exposure to PM10 and associated metals in urban, rural and
      mining activity areas.
AB  - There has been limited study of children's personal exposure to PM10 and
      associated metals in rural and iron ore mining activity areas where PM10
      concentrations can be very high. We undertook a small study of 70 children where
      13 children were recruited in an area of iron ore mining processing and shipping,
      15 children from an area in the same region with no mining activities, and 42
      children in an urban area. Each child provided a 24h personal exposure PM10
      sample, a first morning void urine sample, a hair sample, time activity diary,
      and self administered questionnaire. Children's 24h personal PM10 concentrations
      were low (median of 28 MUg m(-3) in the mining area; 48 MUg m(-3) in the rural
      area and 45 MUg m(-3) in the urban area) with corresponding outdoor PM10
      concentrations also low. Some very high personal PM10 concentrations were
      recorded for individuals (>300 MUg m(-3)) with the highest concentrations
      recorded in the mining and rural areas in the dry season. PM10 concentrations
      were highly variable. Hair aluminium, cadmium and manganese concentrations were
      higher in the iron ore activity area, while hair mercury, copper and nickel
      concentrations were higher in the urban area. Factors such as season and
      ventilation appear to be important but this study lacked power to confirm this.
      These results need to be confirmed by a larger study and the potential for
      absorption of the metals needs to be established along with the factors that
      increase exposures and the potential for health risks arising from exposure.

PMID- 24875922
TI  - Proteolytic activity of Porphyromonas gingivalis attenuates MCP-1 mRNA expression
      in LPS-stimulated THP-1 cells.
AB  - Bacteria can modulate cytokine production of host cells. In this study, we
      examined effects of Porphyromonas gingivalis, an important periodontal pathogen,
      on the cytokine production in lipopolysaccharide (LPS)-stimulated THP-1
      macrophagic cells. A wide range of doses of P. gingivalis increased the tumor
      necrosis factor-alpha (TNF-alpha) production. However, monocyte chemoattractant
      protein-1 (MCP-1) production was substantially suppressed by high doses of P.
      gingivalis and this effect was demonstrated at the mRNA level. Challenges with a
      congenic protease mutant strain did not significantly attenuate the MCP-1 mRNA
      expression and addition of leupeptin, a protease inhibitor, to the cultures
      largely prevented the inhibition of MCP-1 expression by P. gingivalis. Transwell
      experiments showed that direct contact of P. gingivalis with THP-1 cells was not
      required for the MCP-1 inhibition. Furthermore, blockade of internalization of P.
      gingivalis into THP-1 cells had no effect on the MCP-1 inhibition by P.
      gingivalis. Finally, degradation of MCP-1 mRNA in LPS-stimulated THP-1 cells was
      accelerated in the presence of P. gingivalis. These results suggest that the
      proteolytic activity of P. gingivalis attenuate MCP-1 mRNA expression by
      promoting the decay of MCP-1 mRNA in LPS-stimulated THP-1 cells.

PMID- 24875924
TI  - Rare Streptomyces sp. polyketides as modulators of K-Ras localisation.
AB  - Chemical investigations of a soil-derived Streptomyces sp. led to the isolation
      of five new polyketides, (+)-oxanthromicin, (+/-)-hemi-oxanthromicins A/B, (+/-)
      spiro-oxanthromicin A and oxanthroquinone, and the known alkaloid staurosporine,
      and the detection of four new metastable analogues, (+/-)-spiro-oxanthromicins
      B1/B2/C1/C2. Among the compounds tested, SAR investigations established that the
      synthetic oxanthroquinone ethyl ester and 3-O-methyl-oxanthroquinone ethyl ester
      were optimal at mislocalising oncogenic mutant K-Ras from the plasma membrane of
      intact Madin-Darby canine kidney (MDCK) cells (IC50 4.6 and 1.2 MUM), while a sub
      EC50 dose of (+/-)-spiro-oxanthromicin A was optimal at potentiating (750%) the K
      Ras inhibitory activity of staurosporine (IC50 60 pM). These studies demonstrate
      that a rare class of Streptomyces polyketide modulates K-Ras plasma membrane
      localisation, with implications for the future treatment of K-Ras dependent
      cancers. 

PMID- 24875925
TI  - Canadian Headache Society systematic review and recommendations on the treatment
      of migraine pain in emergency settings.
AB  - BACKGROUND: There is a considerable amount of practice variation in managing
      migraines in emergency settings, and evidence-based therapies are often not used
      first line. METHODS: A peer-reviewed search of databases (MEDLINE, Embase,
      CENTRAL) was carried out to identify randomized and quasi-randomized controlled
      trials of interventions for acute pain relief in adults presenting with migraine
      to emergency settings. Where possible, data were pooled into meta-analyses.
      RESULTS: Two independent reviewers screened 831 titles and abstracts for
      eligibility. Three independent reviewers subsequently evaluated 120 full text
      articles for inclusion, of which 44 were included. Individual studies were then
      assigned a US Preventive Services Task Force quality rating. The GRADE scheme was
      used to assign a level of evidence and recommendation strength for each
      intervention. INTERPRETATION: We strongly recommend the use of prochlorperazine
      based on a high level of evidence, lysine acetylsalicylic acid, metoclopramide
      and sumatriptan, based on a moderate level of evidence, and ketorolac, based on a
      low level of evidence. We weakly recommend the use of chlorpromazine based on a
      moderate level of evidence, and ergotamine, dihydroergotamine, lidocaine
      intranasal and meperidine, based on a low level of evidence. We found evidence to
      recommend strongly against the use of dexamethasone, based on a moderate level of
      evidence, and granisetron, haloperidol and trimethobenzamide based on a low level
      of evidence. Based on moderate-quality evidence, we recommend weakly against the
      use of acetaminophen and magnesium sulfate. Based on low-quality evidence, we
      recommend weakly against the use of diclofenac, droperidol, lidocaine
      intravenous, lysine clonixinate, morphine, propofol, sodium valproate and
      tramadol.

PMID- 24875926
TI  - Pathophysiology of hypnic headache.
AB  - BACKGROUND: Hypnic headache (HH) is a rare primary headache disorder that is
      characterized by strictly sleep related headache attacks. PURPOSE: The underlying
      pathophysiology of HH is mainly enigmatic but some clinical characteristics such
      as circadian rhythmicity and caffeine responsiveness may point toward possible
      underlying mechanisms. METHOD: Current studies that deal with the pathophysiology
      of HH are summarized. Data on cerebral imaging, sleep, electrophysiology studies,
      effectiveness of drugs, and symptomatic headache types are discussed to
      illuminate underlying pathophysiologic mechanisms. CONCLUSION: HH can be clearly
      differentiated by its clinical presentation as well as imaging and
      electrophysiological study results from other primary headaches such as migraine
      or cluster headache. The underlying pathophysiology is still enigmatic but a
      hypothalamic involvement seems to be likely.

PMID- 24875927
TI  - Space headache on Earth: head-down-tilted bed rest studies simulating outer-space
      microgravity.
AB  - BACKGROUND: Headache is a common symptom during space travel, both isolated and
      as part of space motion syndrome. Head-down-tilted bed rest (HDTBR) studies are
      used to simulate outer space microgravity on Earth, and allow countermeasure
      interventions such as artificial gravity and training protocols, aimed at
      restoring microgravity-induced physiological changes. OBJECTIVES: The objectives
      of this article are to assess headache incidence and characteristics during
      HDTBR, and to evaluate the effects of countermeasures. METHODS: In a randomized
      cross-over design by the European Space Agency (ESA), 22 healthy male subjects,
      without primary headache history, underwent three periods of -6-degree HDTBR. In
      two of these episodes countermeasure protocols were added, with either
      centrifugation or aerobic exercise training protocols. Headache occurrence and
      characteristics were daily assessed using a specially designed questionnaire.
      RESULTS: In total 14/22 (63.6%) subjects reported a headache during >=1 of the
      three HDTBR periods, in 12/14 (85.7%) non-specific, and two of 14 (14.4%)
      migraine. The occurrence of headache did not differ between HDTBR with and
      without countermeasures: 12/22 (54.5%) subjects vs. eight of 22 (36.4%) subjects;
      p = 0.20; 13/109 (11.9%) headache days vs. 36/213 (16.9%) headache days; p =
      0.24). During countermeasures headaches were, however, more often mild (p = 0.03)
      and had fewer associated symptoms (p = 0.008). CONCLUSIONS: Simulated
      microgravity during HDTBR induces headache episodes, mostly on the first day.
      Countermeasures are useful in reducing headache severity and associated symptoms.
      Reversible, microgravity-induced cephalic fluid shift may cause headache, also on
      Earth. HDTBR can be used to study space headache on Earth.

PMID- 24875928
TI  - Use of mobile phones as a tool for weight loss: a systematic review.
AB  - We conducted a systematic review of the literature on the use of mobile phones
      for weight loss. A total of 43 studies were identified on obese or overweight
      adults, aged 18 years or over. After review, ten articles met the inclusion
      criteria. There were 19-534 participants per study. Participants were from
      European, Asian and North American regions. The mean body mass index (BMI) of the
      subjects varied from 22 to 36 kg/m(2). Two studies used text messaging or
      multimedia messaging. All the other studies used mobile-phone apps or web-based
      programmes that could be accessed from mobile phones as a part of a weight-loss
      intervention or for evaluating their potential for use and their acceptance. Most
      studies lasted 2-4 months and the maximum duration was 1 year. All but two
      studies showed reductions in the participants' bodyweight, BMI, waist
      circumference and body fat in the various interventions. There appeared to be a
      proportional relationship between weight loss and programme use. The programmes
      most benefited those who took a pro-active approach to everyday problems.
      Frequent self-recording of weight seemed to be important, as was the
      personalisation of the intervention (counselling and individualized feedback).
      Finally, a social support system acted as a motivational tool.

PMID- 24875929
TI  - Telemedicine for retinal care in developing nations: the ORBIS Cyber-Sight
      programme, 2003-2011.
AB  - ORBIS International has provided a web-based ophthalmic disease consultation
      service, Cyber-Sight, for developing nations since 2003. The system connects
      partner physicians with mentor physicians. We have reviewed consultations
      concerning retinal cases submitted from June 2003 to December 2011. Of 943
      retinal consultations reviewed, 117 were excluded, mainly for reasons of
      technical limitations at the partner sites. Of the 826 included cases, 504
      patients were male and 322 were female. The average age of the patients was 43
      years (range 2 months to 86 years). Cases were submitted from partner physicians
      in 30 countries, with five countries accounting for 82% of the cases (India,
      Vietnam, Indonesia, China, Jordan). There was a rise in the case submission rate
      to a peak of 251 cases in 2010. The mean consultant response time was 5 days (SD
      9). The mean time to case closure was 19 days (SD 92). The most common diagnoses
      were diabetic retinopathy (n = 101), retinal vascular occlusion (n = 75) and
      retinal detachment (n = 61). The working diagnosis submitted by the partner did
      not match the mentor's diagnosis in 153 cases (19%). The number of incorrect
      initial partner diagnoses demonstrates that the teleretinal programme serves a
      useful diagnostic role for partner physicians. The Cyber-Sight programme is a
      viable method of delivering advanced retinal expertise to partner institutions
      and increasing capacity for partner doctors in the developing world.

PMID- 24875930
TI  - Development of an orthopaedic teleconsulting service in Italy.

PMID- 24875932
TI  - Complete quantum control of exciton qubits bound to isoelectronic centres.
AB  - In recent years, impressive demonstrations related to quantum information
      processing have been realized. The scalability of quantum interactions between
      arbitrary qubits within an array remains however a significant hurdle to the
      practical realization of a quantum computer. Among the proposed ideas to achieve
      fully scalable quantum processing, the use of photons is appealing because they
      can mediate long-range quantum interactions and could serve as buses to build
      quantum networks. Quantum dots or nitrogen-vacancy centres in diamond can be
      coupled to light, but the former system lacks optical homogeneity while the
      latter suffers from a low dipole moment, rendering their large-scale
      interconnection challenging. Here, through the complete quantum control of
      exciton qubits, we demonstrate that nitrogen isoelectronic centres in GaAs
      combine both the uniformity and predictability of atomic defects and the dipole
      moment of semiconductor quantum dots. This establishes isoelectronic centres as a
      promising platform for quantum information processing. 

PMID- 24875933
TI  - Reply to letter to the editor by dr. Dimitrios tsamis.

PMID- 24875931
TI  - Dynamics of HIV latency and reactivation in a primary CD4+ T cell model.
AB  - HIV latency is a major obstacle to curing infection. Current strategies to
      eradicate HIV aim at increasing transcription of the latent provirus. In the
      present study we observed that latently infected CD4+ T cells from HIV-infected
      individuals failed to produce viral particles upon ex vivo exposure to SAHA
      (vorinostat), despite effective inhibition of histone deacetylases. To identify
      steps that were not susceptible to the action of SAHA or other latency reverting
      agents, we used a primary CD4+ T cell model, joint host and viral RNA sequencing,
      and a viral-encoded reporter. This model served to investigate the
      characteristics of latently infected cells, the dynamics of HIV latency, and the
      process of reactivation induced by various stimuli. During latency, we observed
      persistence of viral transcripts but only limited viral translation. Similarly,
      the reactivating agents SAHA and disulfiram successfully increased viral
      transcription, but failed to effectively enhance viral translation, mirroring the
      ex vivo data. This study highlights the importance of post-transcriptional blocks
      as one mechanism leading to HIV latency that needs to be relieved in order to
      purge the viral reservoir. 

PMID- 24875935
TI  - Using portable X-ray fluorescence spectrometry and GIS to assess environmental
      risk and identify sources of trace metals in soils of peri-urban areas in the
      Yangtze Delta region, China.
AB  - Portable X-ray fluorescence (PXRF) spectrometry may be very suitable for a fast
      and effective environmental assessment and source identification of trace metals
      in soils. In this study, topsoils (0-10 cm) at 139 sites were in situ scanned for
      total trace metals (Cr, Cu, Ni, Pb and Zn) and arsenic concentrations by PXRF in
      a typical town in Yangtze Delta region of Jiangsu province, China. To validate
      the utility of PXRF, 53 samples were collected from the scanning sites for the
      determination of selected trace metals using conventional methods. Based on trace
      metal concentrations detected by in situ PXRF, the contamination extent and
      sources of trace metals were studied via geo-accumulation index, multivariate
      analysis and geostatistics. The trace metal concentrations determined by PXRF
      were similar to those obtained via conventional chemical analysis. The median
      concentration of As, Cr, Cu, Ni, Pb and Zn in soils were 10.8, 56.4, 41.5, 43.5,
      33.5, and 77.7 mg kg(-1), respectively. The distribution patterns of Cr, Cu, Ni,
      Pb, and Zn were mostly affected by anthropogenic sources, while As was mainly
      derived from lithogenic sources. Overall, PXRF has been successfully applied to
      contamination assessment and source identification of trace metals in soils.

PMID- 24875936
TI  - China's sustained drive to eliminate neglected tropical diseases.
AB  - Non-communicable diseases dominate the public health arena in China, yet
      neglected tropical diseases (NTDs) are still widespread and create a substantial
      burden. We review the geographical distribution, prevalence, and epidemic
      characteristics of NTDs identified in China caused by helminths, protozoa,
      bacteria, and viruses. Lymphatic filariasis was eliminated in 2007, but
      schistosomiasis still affects up to 5% of local village residents in some endemic
      counties with around 300 000 people infected. China harbours more than 90% of the
      world's burden of alveolar echinococcosis and food-borne zoonoses are emerging.
      In 2010, the overall prevalence of soil-transmitted helminth infections caused by
      Ascaris lumbricoides, Trichuris trichiura, and hookworm was 11.4%, with 6.8% of
      these infections caused by A lumbricoides. Corresponding figures for food-borne
      trematodiasis, echinococcosis, and cysticercosis are more than 5%. Dengue,
      leishmaniasis, leprosy, rabies, and trachoma exist in many areas and should not
      be overlooked. Transmission of vector-borne diseases can be interrupted;
      nevertheless, epidemics occur in remote areas, creating a challenge for
      surveillance and control. Rigorous surveillance, followed by immediate and
      integrated response packages tailored to specific social and ecological systems,
      is essential for progress towards the elimination of NTDs in China. 

PMID- 24875938
TI  - Synergy between experimental and theoretical methods in the exploration of
      homogeneous transition metal catalysis.
AB  - In this Perspective, we will focus on the use of both experimental and
      theoretical methods in the exploration of reaction mechanisms in homogeneous
      transition metal catalysis. We briefly introduce the use of Hammett studies and
      kinetic isotope effects (KIE). Both of these techniques can be complemented by
      computational chemistry - in particular in cases where interpretation of the
      experimental results is not straightforward. The good correspondence between
      experiment and theory is only possible due to recent advances within the applied
      theoretical framework. We therefore also highlight the innovations made in the
      last decades with emphasis on dispersion-corrected DFT and solvation models. The
      current state-of-the-art is highlighted using examples from the literature with
      particular focus on the synergy between experiment and theory. 

PMID- 24875937
TI  - Role of glucocorticoids and Toxoplasma gondii infection on murine intestinal
      epithelial cells.
AB  - Glucocorticoids (GCs) are stress hormones secreted in response to perceived
      psychological and or physiological stress. GCs have been shown to reduce tissue
      inflammation by down-regulating the production of inflammatory chemokines
      produced by epithelial cells. The protozoan parasite Toxoplasma gondii is known
      to increase cytokine, chemokine, and Toll-like receptors (TLRs) expression in
      parasite infected mouse intestinal epithelial cells (IECs). We sought to analyze
      the role of an anti-inflammatory protein, glucocorticoid-induced leucine zipper
      (GILZ) in MODE-K cells during infection with T. gondii. GILZ expression in MODE-K
      cells was assessed by PCR and immunoblotting after stimulation with GCs
      (corticosterone, CORT) or T. gondii infection. GILZ mRNA was constitutively
      expressed in MODE-K cells but not its protein product. While infection and pre
      exposure to CORT decreased GILZ isoforms of 28 and 17 kD, the presence of CORT
      during infection increased levels of 17 kD isoform. Infected cells treated with
      CORT had decreased expression of chemokines (IP-10/CXCL10, MCP-1/CCL2, MIP
      2/CXCL8) while their expression was increased when endogenous GILZ was removed by
      siRNA treatment. GILZ up-regulation during infection may serve as a mechanism to
      decrease epithelial cell responses and facilitate parasite replication.

PMID- 24875939
TI  - Positron emission tomography and stage migration in head and neck cancer.
AB  - IMPORTANCE: Since 2001, there has been a rapid adoption of positron emission
      tomography (PET) for diagnosis and American Joint Committee on Cancer (AJCC)
      staging of head and neck cancer (HNC) without data describing improved clinical
      outcomes. OBJECTIVE: To determine the association between increased use of PET
      and stage and/or survival for patients with HNC in the managed care environment.
      DESIGN, SETTING, AND PARTICIPANTS: Adult patients diagnosed as having HNC (n =
      958) from 2000 to 2008 at 4 integrated health systems were identified via tumor
      registries linked to administrative data. The AJCC stage distribution, patient
      and treatment characteristics, and survival between pre-PET era (2000-2004) vs
      PET era (2005-2008) and use of PET vs no use of PET during the PET era were
      compared. The AJCC stages were categorized to represent localized (stage I or
      II), locally advanced (stage III, IVA, or IVB), and metastatic (stage IVC)
      disease. INTERVENTIONS: Treatments were determined by billing codes for surgery,
      radiation treatment, and chemotherapy. MAIN OUTCOMES AND MEASURES: The primary
      outcome for this study was the use of PET. Secondary outcomes included treatment
      received and 2-year survival. A logit model estimated the effects of PET on
      diagnosis of locally advanced disease. Kaplan-Meier estimates described overall
      survival differences between PET and non-PET. Cox regression evaluated the
      association of PET on survival in patients with locally advanced disease.
      RESULTS: An association between PET and locally advanced disease was found (odds
      ratio, 2.86 [95% CI, 1.90-4.29) (P < .001). Two-year overall survival for
      patients with locally advanced disease with and without PET was 52% and 32%,
      respectively (P = .004), but there was no difference for all stages (P = .69). On
      Cox proportional hazard regression, PET had no association with survival in
      patients with locally advanced disease (hazard ratio, 1.208 [95% CI, 0.778
      1.877]) (P = .40). CONCLUSIONS AND RELEVANCE: The increasing use of PET among
      patients with HNC is associated with a greater number of patients with higher
      stage disease and a dilution of the population with higher-stage disease with
      patients who have a better prognosis. Thus, the improved survival in patients
      with locally advanced disease likely reflects selection bias and stage migration.
      Further research on PET use among patients with HNC is necessary to determine if
      it results in improved treatment for individual patients.

PMID- 24875941
TI  - Infrapatellar fat pad osteochondroma: three cases and a systematic review.
AB  - Extraskeletal para-articular osteochondromas of the infrapatellar fat pad are
      unique soft-tissue tumors whose etiology and clinical history remain poorly
      understood. We report three cases and a systematic review of the literature.
      Three females, aged 47, 54, and 70 years, presented with pain and a parapatellar
      knee mass. All three underwent marginal excision with no complications and no
      recurrence. In the literature, 32 reports describing 42 cases were identified.
      Mean age at presentation was 51.1 years (range: 12-75). There were 25 females and
      20 males. Seven patients (15.6%) had a history of antecedent trauma. Mean
      duration of presenting symptoms was 63.9 months (range: 2-300). All patients
      except for one underwent open excision. Mean follow-up was 14.9 months (range: 3
      96). There were no reports of recurrence or malignant transformation. Para
      articular extraskeletal osteochondromas of the infrapatellar fat pad have a
      benign clinical history regardless of whether they are managed by arthroscopic or
      open marginal excision. 

PMID- 24875940
TI  - Evaluation of genetic association of the INK4 locus with primary open angle
      glaucoma in East Indian population.
AB  - INK4 locus at chromosome 9p21 has been reported to be associated with primary
      open angle glaucoma (POAG) and its subtypes along with the associated optic disc
      parameters across the populations of European, Japanese and African ancestries.
      The locus encodes three tumor suppressor genes namely CDKN2A, ARF, CDKN2B and a
      long non-coding RNA CDKN2B-AS1 (also known as ANRIL). Here, we report association
      study of 34 SNPs from INK4 locus with POAG in a population of Indo-European
      ancestry from the eastern part of India (350 patients and 354 controls). With 81%
      power to detect genetic association we observed only nominal association of
      rs1011970 (uncorrected p = 0.048) with POAG and rs10120688 (uncorrected p =
      0.048) in patients without a high intra-ocular pressure (IOP<21 mm of Hg)
      compared to controls. This study, in contrast to the previous reports, suggests
      lack of significant genetic association of INK4 locus with POAG in East Indian
      population which needs to be replicated in larger studies in diverse world
      populations. 

PMID- 24875942
TI  - Readmission rates for cruciate-retaining total knee arthroplasty.
AB  - Currently, the readmission rates for patients treated with cruciate-retaining
      (CR) prostheses have not been widely evaluated. The purpose of this study was to
      report on readmission rates after CR total knee arthroplasties (TKAs) and to
      evaluate the potential contributing factors for these events. We reviewed a
      prospectively collected database of 412 patients (441 TKAs) at 11 institutions.
      This included 170 men and 242 women who had a mean age of 66 years. Overall,
      there were 15 unplanned readmissions (3.4%) in 15 patients during the first 90
      days following discharge after the index arthroplasty procedure. This included a
      readmission rate of 2% at 30 days and 3.2% at 60 days after discharge. Of the 15
      readmissions, nine were due to general medical-related causes, while the other
      six events were as a result of operative site or surgery-related complications.
      However, readmitted patients had a 29.8% higher incidence of cardiovascular
      disorders at baseline compared with the patients who were not readmitted. The 30-
      and 90-day readmission rates for patients treated with cruciate-retaining (CR)
      TKAs are encouraging since these are comparable to previously reported
      readmission rates of other prostheses. Unplanned hospital readmissions are
      expensive and an undesired outcome for the patient, physician, and health care
      system. The authors believe that the positive mid-term clinical performance of
      this CR prosthesis may have contributed to the lower readmission rates, and
      believe that this is a stepping stone for further larger prospective studies and
      is necessary to better evaluate these findings. 

PMID- 24875943
TI  - Conditioned medium from spinal cord cells stimulates DRG cells to migrate,
      cluster and rearrange in dissociated cell cultures.
AB  - Murine spinal sensory neurons migrate in dissociated cell culture resulting in
      convergence, divergence and cluster rearrangement by the cells. We found that
      culture medium which had been conditioned by the growth of spinal cord cells
      stimulated the convergence of DRG cells into clusters. Binuclear sensory neurons,
      which are often found in these cultures, failed to migrate or proceed with
      mitotic cleavage during the 2 weeks of observation. We conclude that these cells
      were arrested in mitosis during or shortly after their removal from the 13-day
      old embryo. 

PMID- 24875944
TI  - Developmental effects of early postnatal treatment of rats with prochlorperazine.
AB  - This study examined effects of neonatal prochlorperazine in rats tested as adults
      in a variety of behaviors. The drug exposure impaired open field behavior during
      treatment neonatally. However, no differences in open field behavior were
      observed in adulthood. Adult females that had received drug were less efficient
      in obtaining food reinforcement in a conditioned maze performance than were
      respective controls and showed a slight increase in motor activity during
      accommodation. d-Amphetamine-induced motor activity was greater in both treated
      males and females relative to respective controls. Spaced trials in shuttle-box
      avoidance uncovered an avoidance decrement in the treated females only. This drug
      treatment appears to cause subtle changes in brain development in the rat. 

PMID- 24875945
TI  - Activity of muscle cultures measured by 2-deoxyglucose uptake.
AB  - Glucose consumption of skeletal muscle differentiated in vitro was studied under
      various experimental conditions by means of the [(3)H]deoxyglucose ([(3)H]DG)
      uptake technique. The results show that glucose uptake by skeletal muscle is a
      function of its activity; when the muscle is electrically stimulated to contract
      the uptake of [(3)H]DG is increased, and when spontaneous activity is inhibited,
      the uptake of [(3)H]DG is decreased. While electrical stimulation (ES) did not
      affect the uptake of 3-O-methyl-glucose (3-OMG), DG uptake was enhanced in spite
      of the presence of cycloheximide in electrically stimulated cultures, suggesting
      that muscle contraction probably activates the enzyme hexokinase. Thus our data
      show that the uptake of [(3)H]DG can be a tool for measuring muscle contraction. 

PMID- 24875946
TI  - Intraocular transplants of olfactory neuroepithelium in rat.
AB  - Olfactory neuroepithelium of neonatal rat pups has been transplanted in the
      anterior chamber of the eye of adult rats. Structural and ultrastructural
      observations at 5, 10, 30, 50, 90 and 120 days show that mature neurons
      degenerate rapidly in the expiant (before 5 days) while the basal elements
      proliferate and produce a new population of young neurons between 1 and 10 days.
      At longer survivals (30-120 days) it is seen that the neurons acquire
      morphological maturity, and positivity to the olfactory marker protein, as
      demonstrated by immunohistochemical methods. Our observations show that new
      neurons can be generated in the transplanted neuroepithelium and that their
      generation and maturation occurs in the absence of connections with a brain
      target. 

PMID- 24875947
TI  - A comparison of the regional ontogenesis of nicotine- and muscarine-like binding
      sites in mouse brain.
AB  - The postnatal development of the cholinergic neurotransmitter system was studied
      in the cortex, hippocampus, midbrain and cerebellum of 3-, 7-, 12-, 17- and 30
      day-old NMRI mice. The concentration of muscarine-like binding sites determined
      with [(3)H]quinuclidinyl benzilate as a ligand increased progressively with age.
      A similar developmental pattern was found for the activity of a presynaptic
      marker, choline acetyltransferase (ChAT). When expressed as a percentage of the
      values for 30-day-old mice, however, the muscarine-like receptors were parallel
      but preceding the development of ChAT in all the brain regions studied. The
      concentration of nicotine-like binding sites studied with [(3)H]alpha-bungaro
      toxin as a ligand gradually increased with age in the cortex, hippocampus and
      midbrain, with a peak between days 7 and 12, followed by a decrease towards day
      30. With [(3)H]tubocurarine as a ligand, on the other hand, the concentration of
      nicotine-like binding sites was in general high at 3 days and gradually decreased
      with age, suggesting that different subpopulations of nicotine-like receptors
      might be determined when the two ligands are used. 

PMID- 24875948
TI  - Biochemical compensation and recovery following temporary inhibition of ornithine
      decarboxylase during the development of rat cerebellar cortex.
AB  - Specific inhibition of ornithine decarboxylase selectively in the developing rat
      cerebellum was achieved within 10 min after intrathecal injection of alpha
      difluoromethylornithine. Twelve hours later the activity started to increase,
      passed control levels between 2 and 3 days, continued to increase and reached its
      peak values by day 3 (when animals were 10 days old), 3 days after peak control
      values. Ornithine decarboxylase activity then declined and attained low adult
      values simultaneously with controls. Glutamic acid decarboxylase activity, a
      marker of gabaergic neurons maturation, declined to a nadir at 3 days
      postinjection, and then was elevated transiently above control levels with a peak
      at 11 days postinjection. We conclude that after such a temporary insult
      neuroblasts of the cerebellar cortex are capable of full recovery, which is
      apparent by a reversible reduction in ornithine decarboxylase and glutamic acid
      decarboxylase activities followed by a transient compensatory elevation in both
      enzymes. 

PMID- 24875949
TI  - Effects of extended periods of reserpine and alpha-methyl-p-tyrosine treatment on
      the development of the putamen in fetal rabbits.
AB  - Developing nigrostriatal neuroblasts exhibit catecholamine-induced fluorescence
      before their axons have left the vicinity of the cell bodies. To evaluate
      possible developmental effects of dopamine, we have used reserpine and alpha
      methyl-p-tyrosine to deplete dopamine chronically during the development of these
      axons. We found that dopamine-induced fluorescence was either absent or markedly
      decreased in the fetal putamens. To determine whether the absence of fluorescence
      was due to a reduction of dopamine terminals, the uptake of tritium-labeled
      dopamine was measured in the putamen. Uptake of labeled dopamine was
      significantly depressed in reserpine-treated fetuses to 70% of that of controls;
      however, no depression of labeled dopamine was found in the alpha-methyl-p
      tyrosine-treated fetuses. After both drug treatments, the striatal perikarya were
      less mature than those of controls. Although we cannot rule out possible non
      specific or toxic effects of the drugs, these observations support the conclusion
      that presynaptic dopamine may be important for development of target neurons in
      the neostriatum. 

PMID- 24875950
TI  - Cultured embryonic non-innervated mouse muzzle is capable of generating a whisker
      pattern.
AB  - The whisker pattern on the muzzle of the mouse is mapped in the contralateral
      parietal neocortex, each whisker follicle projecting to its own multineuronal
      unit ('barrel'). To determine the role, if any, of the peripheral innervation in
      the establishment of the vibrissal array, we cultured non-innervated prospective
      whiskerpads from 9- and 10-day-old embryos, mostly on chorioallantoic membrane.
      The results show that skin, alone, is capable of generating the whisker pattern,
      thus adducing a strong argument for the hypothesis that the central brain maps
      have their origin in the periphery. 

PMID- 24875951
TI  - Transcriptional control of dendritic cell differentiation.
AB  - Dendritic cells (DCs) are professional antigen presenting cells involved
      critically not only in provoking innate immune responses but also in establishing
      adaptive immune responses. Dendritic cells are heterogenous and divided into
      several subsets, including plasmactyoid DCs (pDCs) and several types of
      conventional DCs (cDCs), which show subset-specific functions. Plasmactyoid DCs
      are featured by their ability to produce large amounts of type I interferons
      (IFNs) in response to nucleic acid sensors, TLR7 and TLR9 and involved in anti
      viral immunity and pathogenesis of certain autoimmune disorders such as
      psoriasis. Conventional DCs include the DC subsets with high crosspresentation
      activity, which contributes to anti-viral and anti-tumor immunity. These subsets
      are generated from hematopoietic stem cells (HSCs) via several intermediate
      progenitors and the development is regulated by the transcriptional mechanisms in
      which subset-specific transcription factors play major roles. We have recently
      found that an Ets family transcription factor, SPI-B, which is abundantly
      expressed in pDCs among DC subsets, plays critical roles in functions and late
      stage development of pDCs. SPI-B functions in cooperation with other
      transcription factors, especially, interferon regulatory factor (IRF) family
      members. Here we review the transcription factor-based molecular mechanisms for
      generation and functions of DCs, mainly by focusing on the roles of SPI-B and its
      relatives. 

PMID- 24875953
TI  - Synergistic catalysis: highly diastereoselective benzoxazole addition to Morita
      Baylis-Hillman carbonates.
AB  - An expedited method has been developed for the diastereoselective synthesis of
      highly functionalized alkyl-azaarene systems with good yields and high
      diastereoselectivities (>15 : 1 dr). The methodology includes a synergistic
      catalysis event involving organometallic (10 mol% AgOAc) activation of an alkyl
      azaarene and Lewis base (10 mol% DABCO) activation of a Morita-Baylis-Hillman
      carbonate. The structure and relative configuration of a representative product
      were confirmed by X-ray analysis. 

PMID- 24875952
TI  - 3D landmarking in multiexpression face analysis: a preliminary study on eyebrows
      and mouth.
AB  - The application of three-dimensional (3D) facial analysis and landmarking
      algorithms in the field of maxillofacial surgery and other medical applications,
      such as diagnosis of diseases by facial anomalies and dysmorphism, has gained a
      lot of attention. In a previous work, we used a geometric approach to
      automatically extract some 3D facial key points, called landmarks, working in the
      differential geometry domain, through the coefficients of fundamental forms,
      principal curvatures, mean and Gaussian curvatures, derivatives, shape and
      curvedness indexes, and tangent map. In this article we describe the extension of
      our previous landmarking algorithm, which is now able to extract eyebrows and
      mouth landmarks using both old and new meshes. The algorithm has been tested on
      our face database and on the public Bosphorus 3D database. We chose to work on
      the mouth and eyebrows as a separate study because of the role that these parts
      play in facial expressions. In fact, since the mouth is the part of the face that
      moves the most and affects mainly facial expressions, extracting mouth landmarks
      from various facial poses means that the newly developed algorithm is pose
      independent. NO LEVEL ASSIGNED: This journal requires that authors assign a level
      of evidence to each submission to which Evidence-Based Medicine rankings are
      applicable. This excludes Review Articles, Book Reviews, and manuscripts that
      concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies.
      For a full description of these Evidence-Based Medicine ratings, please refer to
      the Table of Contents or the online Instructions to Authors
      http://www.springer.com/00266 .

PMID- 24875955
TI  - Timing and predictors of return to short-term functional activity in adolescent
      idiopathic scoliosis after posterior spinal fusion: a prospective study.
AB  - STUDY DESIGN: Prospective study. OBJECTIVE: To assess the timing and predictors
      of return to short-term functional activity in patients with adolescent
      idiopathic scoliosis (AIS) after posterior spinal fusion (PSF). SUMMARY OF
      BACKGROUND DATA: Few studies have examined the timing and rate of return to short
      term functional activity in patients with AIS after PSF. No study has yet
      evaluated the timing and factors that predict a delayed return to school/college-
      a topic relevant to patients who have had or anticipate having spinal fusion, and
      their treating surgeons. METHODS: Seventy-seven eligible subjects with AIS who
      underwent PSF and correction (January 2010 to April 2012) were followed up until
      return to the functional outcomes under analysis. Timing of return to
      school/college and physical activity, as per the patients' preoperative level or
      better, was assessed. Binary logistic regression analysis was used to determine
      predictors of delayed return to school/college full-time (>16 wk) and
      unrestricted physical activity (>32 wk) relative to sociodemographic,
      anthropometric, radiographical, clinical, and surgical factors. In the present
      study, a "delayed" return to all the functional outcomes recorded was defined as
      "greater than the 75th percentile" of the continuous distribution. RESULTS: Mean
      follow-up was 12.8 months (SD, 5.7). Mean age was 15.04 years (SD, 1.89). The
      median time to return to school/college full-time (n = 75) was 10 weeks; the
      majority returned by 16 weeks (77.3%). Preoperative curves greater than 70
      degrees  (relative risk, 3.38; P = 0.008), postoperative weight loss greater than
      5 kg (relative risk, 3.02; P = 0.012), and minor perioperative respiratory
      complication incidence (relative risk, 2.89; P = 0.024) independently predicted
      delayed return to school/college full-time. By 24 and 52 weeks, 51.4% and 88.5%
      of subjects, respectively, returned to unrestricted physical activity. At final
      follow-up, nonreturn to unrestricted physical activity was identified in only 3
      subjects (4.3%) because of chronic back pain. CONCLUSION: The majority of
      patients with AIS can expect to return to school/college full-time by 16 weeks
      and unrestricted physical activity by 52 weeks after PSF. Preoperative curves
      greater than 70 degrees , postoperative weight loss greater than 5 kg, and minor
      perioperative respiratory complication incidence independently predicted a
      delayed return to school/college full-time. These findings add to the current
      knowledge base regarding actual versus anticipated timing of return to short-term
      functional outcomes in this population. LEVEL OF EVIDENCE: 3.

PMID- 24875956
TI  - Efficacy of transcranial motor evoked potentials, mechanically elicited
      electromyography, and evoked electromyography to assess nerve root function
      during sustained compression in a porcine model.
AB  - STUDY DESIGN: This is an animal experiment using transcranial motor evoked
      potentials (TcMEPs), mechanically elicited electromyographic (EMG) responses, and
      evoked EMG responses during nerve root compression in a pig model. OBJECTIVE: To
      compare these 3 electrophysiological measures for compression applied to a lumbar
      nerve root. SUMMARY OF BACKGROUND DATA: Lumbar nerve root injury may result in
      motor weakness in up to 30% of spinal deformity cases. Compressive injury may
      occur during the surgical approach, decompression, and manipulation of the spine.
      Using an established porcine model, we examined the changes to TcMEPs,
      mechanically elicited EMG responses, and evoked EMG responses during varied
      compressive forces. METHODS: TcMEPs, mechanically elicited EMG responses, and
      evoked EMG responses were recorded for the tibialis anterior muscle in 16
      experiments. Precompression TcMEP and nerve root stimulation threshold (NRT) were
      obtained. The dominant root was compressed at 1 N (n = 8) or 2 N (n = 8) for 10
      minutes. TcMEP was recorded every minute during compression, and TcMEP and NRT
      were recorded after both compression and 10 minutes of recovery. RESULTS: After
      10 minutes of 1-N compression, TcMEP amplitude of the tibialis anterior muscle
      decreased to 69% +/- 13% of baseline (P < 0.02 vs. baseline). The mean NRT
      increased to 645% +/- 433% (P < 0.02 vs. baseline NRT). After the recovery
      period, TcMEP in the 1-N group returned to 98% +/- 11% of baseline (P = 0.36 vs.
      baseline). After 10 minutes of 2-N compression, TcMEPs from the tibialis anterior
      muscle decreased to 27% +/- 15% of baseline (P < 0.02 vs. baseline). After the
      recovery period, TcMEP in the 2-N group returned to 30% +/- 10% of baseline (P <
      0.02 vs. baseline). Tonic EMG activity was observed in 3 nerve roots compressed
      at 2 N. CONCLUSION: Compression at 1 and 2 N produced consistent changes in
      TcMEPs and EMG responses. TcMEP monitoring is sensitive to an increase in
      compressive force. TcMEP amplitude change was correlated to the force applied and
      the ability of the nerve root to recover. Mechanically elicited EMG responses
      were not sensitive to nerve root compression. LEVEL OF EVIDENCE: N/A.

PMID- 24875957
TI  - Case reviews of infections of the spine in patients with a history of solid organ
      transplantation.
AB  - STUDY DESIGN: Retrospective clinical case series. OBJECTIVE: To report on the
      epidemiological, microbiological, and clinical characteristics of spinal
      infections in patients who have undergone solid organ transplantation. SUMMARY OF
      BACKGROUND DATA: Spine infections remain a therapeutic challenge, particularly in
      patients who are immunocompromised. Solid organ transplant patients represent a
      growing population of immunocompromised hosts. To our knowledge, no previous
      reports have examined the clinical characteristics spinal infections in this at
      risk population in a systematic fashion. METHODS: The records of patients with a
      history of solid organ transplantation from January 2007 through December 2012
      were identified using Current Procedural Terminology procedure codes. Patients
      with spine infections who have received transplants were then identified using
      International Classification of Diseases, Ninth Revision codes for spine
      infection. In addition to demographic data, we recorded medical comorbidities,
      immunosuppressant medications, laboratory results, culture data, treatment
      received, and short-term results. RESULTS: During this 6-year period, 2764 solid
      organ transplants were performed at our institution. Of this cohort, 6 patients
      (0.22%) were treated for a spinal infection. Patient's age ranged from 51 to 80
      years (mean, 63 yr). All spine infections occurred within 1 year after organ
      transplantation. All patients had an elevated erythrocyte sedimentation rate.
      Only 1 patient had an elevated white blood cell count. The most common organisms
      were Escherichia coli and Staphylococcus. Four patients required surgical
      treatment. All patients had complete resolution of symptoms. CONCLUSION: Our data
      suggest that patients with a history of solid organ transplantation may be more
      susceptible to developing spine infections than the general population. The most
      common organisms in our cohort were E. coli and Staphylococcus. Spine infections
      caused by atypical organisms do also occur in the organ transplant population, as
      is the case in other immunocompromised patients. The identification of these
      organisms and timely institution of treatment remains critical in the management
      of this at-risk population. LEVEL OF EVIDENCE: 4.

PMID- 24875958
TI  - Primary stiffness of a modified transforaminal lumbar interbody fusion cage with
      integrated screw fixation: cadaveric biomechanical study.
AB  - STUDY DESIGN: In vitro biomechanical study using human fresh-frozen vertebrae.
      OBJECTIVE: To investigate the influence of the additional screw fixation on the
      stability of a noncommercially available prototype transforaminal lumbar
      interbody fusion (TLIF) cage, when used as a stand-alone fusion device and in
      combination with pedicle screws (PSs). SUMMARY OF BACKGROUND DATA: Generally
      interbody fusion cages are supplemented by additional fixation devices such as
      PS. However, such posterior instrumented techniques are associated with
      additional soft-tissue trauma and potentially increased complication rate. To
      limit such drawbacks, a conventional posterior TLIF cage was modified to allow
      supplemental screw fixation to the adjacent vertebral bodies, to increase initial
      stiffness and possibly allow as a stand-alone posterior interbody cage. METHODS:
      Six monosegmental lumbar spine segments were loaded in a spine simulator with
      pure bending moments of 7.5 Nm in lateral bending, flexion/extension, and axial
      rotation. The following paradigms were tested: intact spines; a destabilized
      spine (i.e., after discectomy and unilateral facetectomy); and the modified TLIF
      cage with (i.e., fixed TLIF cage) and without (i.e., TLIF cage) integrated screw
      fixation as a stand-alone model and with and without additional posterior
      fixation with bilateral PS. The range of motion (RoM) was recorded by a 3
      dimensional motion analysis system. RESULTS: The TLIF cage with integrated screw
      fixation had minimal additional stabilizing effect in all motion planes with or
      without supplemental PS fixation. Moreover, compared with the intact spines, the
      stand-alone TLIF cage with and without integrated screw fixation did not reduce
      the RoM in any of the 3 motion planes. Comparison of the TLIF cage with
      integrated screw fixation to the TLIF cage supplemented with PS showed a
      significantly greater RoM in all testing conditions (P < 0.05). CONCLUSION: In
      several testing paradigms, the prototype TLIF cage with the integrated screw
      fixation had limited effect in reducing RoM and providing stability. The PS was
      the main contributor in reducing RoM in the destabilized spine and remains the
      current "gold standard" in posterolateral spinal fixation. LEVEL OF EVIDENCE:
      N/A.

PMID- 24875959
TI  - The cutoff amplitude of transcranial motor evoked potentials for transient
      postoperative motor deficits in intramedullary spinal cord tumor surgery.
AB  - STUDY DESIGN: Retrospective clinical study of intraoperative transcranial motor
      evoked potential (TcMEP) amplitudes and postoperative motor deficits (PMDs).
      OBJECTIVE: To determine the quantifiable cutoff amplitude of TcMEP for predicting
      transient PMDs in intramedullary spinal cord tumor (IMSCT) surgery. SUMMARY OF
      BACKGROUND DATA: The "presence or absence" criterion is reliable and widely used
      the alarm criterion for preventing permanent PMDs in IMSCT surgery. However, we
      wanted to prevent PMDs even if it is transient. The cutoff amplitude for
      transient PMDs should be identified. METHODS: We conducted a retrospective study
      to identify the cutoff amplitude for predicting transient PMDs in IMSCT surgery.
      Thirty-seven patients were included in the study. We examined intraoperative
      electrophysiological changes and perioperative motor status in these patients.
      Receiver operating characteristic analyses were performed to identify the cutoff
      amplitudes for predicting transient PMDs in IMSCT surgery. The incidence of PMDs
      and cutoff TcMEP amplitude in cervical and thoracic lesions were compared.
      RESULTS: Thirteen cases demonstrated transient PMDs. Among 280 monitorable
      muscles in 37 cases, 51 muscles in 13 patients showed PMDs. Through receiver
      operating characteristic analysis, the relative and the absolute cutoff
      amplitudes at the intraoperative point of deterioration were identified to be 12%
      residual of baseline amplitude and 3.2 MUV, respectively. Sensitivity/specificity
      for those cutoff points are 86%/74% and 88%/78%, respectively. The incidence of
      PMD was significantly higher, and the cutoff amplitude was lower in the thoracic
      lesions than in the cervical lesions. CONCLUSION: We determined the cutoff TcMEP
      amplitude for predicting transient PMDs in IMSCT surgery. The cutoff amplitude
      for the cervical lesions was higher than that for the thoracic lesions. The
      results suggest the need for setting different alarm criteria in different level
      of spine. LEVEL OF EVIDENCE: 3.

PMID- 24875960
TI  - Preoperative serum albumin level as a predictor of postoperative complication
      after spine fusion.
AB  - STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To investigate the
      association between preoperative baseline serum albumin and postoperative
      surgical complication. SUMMARY OF BACKGROUND DATA: The prevalence of malnutrition
      in the hospitalized patient population has only been recently recognized.
      Preoperative hypoalbuminemia (serum albumin <3.5 g/dL) has been shown to be
      associated with increased morbidity and mortality rates. The prognostic
      implications and significance of hypoalbuminemia after spine fusion surgery
      remain unknown. In this study, we assess the predictive value of preoperative
      nutritional status (serum albumin level) on postoperative complication rates.
      METHODS: The medical records of 136 consecutive patients undergoing spine fusion
      at Duke University Medical Center were reviewed. Preoperative serum albumin level
      was assessed on all patients and used to quantify nutritional status. Albumin
      less than 3.5 g/dL was recognized as hypoalbuminemia (malnourished). Patient
      demographics, comorbidities, and postoperative complication rates were collected.
      Patients were also stratified into 2 groups based on their cause, namely elective
      degenerative/deformity versus nonelective cases. The association between
      preoperative serum albumin level and postoperative complication was assessed via
      logistic regression analysis. RESULTS: Overall, 40 (29.4%) patients experience at
      least 1 postoperative complication. Patients undergoing elective surgery had more
      complications based on preoperative albumin levels (malnourished patients: 35.7%
      vs. nourished patients: 11.7%, P = 0.03), whereas those undergoing nonelective
      surgery had similar complication rates (malnourished patients: 46.5% vs.
      nourished patients: 42.1%, P = 0.75). For patients undergoing elective spinal
      surgery, logistic regression with and without propensity score adjustment for
      risk factors, demonstrated that preoperative serum albumin level was a
      significant predictor of postoperative complications (OR: 4.21; 95% CI: 1.09
      16.19; P = 0.04) and (OR: 4.54; 95% CI: 1.17-19.32; P = 0.04), respectively.
      CONCLUSION: Preoperative hypoalbuminemia is an independent risk factor for
      postoperative complications after elective spine surgery for degenerative and
      deformity causes, and should be used more frequently as a prognostic tool to
      detect malnutrition and risk of adverse surgical outcomes. LEVEL OF EVIDENCE: 2.

PMID- 24875961
TI  - Incidence and risk factors for early wound complications after spinal arthrodesis
      in children: analysis of 30-day follow-up data from the ACS-NSQIP.
AB  - STUDY DESIGN: Retrospective review of prospectively collected data. OBJECTIVE: To
      determine the incidence and risk factors for 30-day wound complication after
      spinal arthrodesis in pediatric patients. SUMMARY OF BACKGROUND DATA: Although
      multiple prior studies have reported on wound complications in pediatric spine,
      the majority have been single-center retrospective series. METHODS: The National
      Surgical Quality Improvement Program (NSQIP) employs on-site personnel to
      prospectively collect 30-day morbidity data from 50 pediatric centers. Year 2012
      was the first year of enrollment, and 1915 cases with thoracic or lumbar spinal
      fusion were included. Patients were divided into cohorts of those with and
      without a wound complication, with univariate and multivariate analyses used to
      identify risk factors. A P value of less than 0.05 was considered significant.
      RESULTS: Wound complications occurred in 67 patients (3.5%). The incidence was
      significantly higher in patients with congenital (4.35%) or neuromuscular (4.67%)
      diagnoses, as opposed to idiopathic (2.7%) or infantile (1.61%). Procedures with
      fusions extending to the pelvis (9.91%) or an osteotomy (4.99%) were associated
      with higher risk. Longer hospital lengths of stay, increased operative time,
      increased patient body mass index, and patients with cardiac, gastrointestinal,
      neurological, or pulmonary comorbidities were also associated with a higher risk.
      In the multivariate analysis, a body mass index of more than 30 kg/m2, patients
      with cardiac risk factors, and fusions extending to the pelvis were independent
      risk factors. CONCLUSIONS: Data from this large prospective multicenter study
      confirm that the incidence of early wound complications in pediatric spine
      surgery is low. Patients with a fusion extending to the pelvis, obese patients,
      and patients with significant cardiac conditions were independently associated
      with higher risk for this complication. These data should be useful for patients'
      counseling and for preoperative risk stratification. Interventions for minimizing
      wound complication risk may be most applicable to the high-risk groups identified
      here. LEVEL OF EVIDENCE: 2.

PMID- 24875962
TI  - Incidence of sacral fractures and in-hospital postoperative complications in the
      United States: an analysis of 2002-2011 data.
AB  - STUDY DESIGN: Retrospective study of an administrative database. OBJECTIVE: To
      estimate the incidence of sacral fractures in the United States and report short
      term outcomes after their surgical management. SUMMARY OF BACKGROUND DATA: The
      incidence of sacral fractures in the United States is currently unknown, and
      these lesions have been associated with significant morbidity after their
      surgical management. METHODS: This study used the Nationwide Inpatient Sample
      database for the years 2002-2011. All patients with a primary discharge diagnosis
      of a sacral fracture with and without a neurological injury were identified using
      International Classification of Diseases, Ninth Revision, Clinical Modification
      codes. Patients with a diagnosis of osteoporosis or pathological fracture were
      excluded. A stepwise multivariate logistic regression analysis was performed to
      identify factors associated with an in-hospital complication. RESULTS: During the
      study period, 10,177 patients with a nonosteoporotic sacral fracture were
      identified, of whom 1002 patients underwent surgery. Between 2002 and 2011, the
      estimated incidence of sacral fractures increased from 0.67 per 100,000 persons
      to 2.09 (P < 0.001). Similarly, the rate of surgical treatment for sacral
      fractures increased from 0.05 per 100,000 persons in 2002 to 0.24 per 100,000 in
      2011 (P < 0.001). Complications occurred in 25.95% of patients and remained
      steady over time (P = 0.992). Average length of stay significantly decreased from
      11.93 days to 9.66 days in the 10-year period (P = 0.023). The independent
      factors associated with an in-hospital complication were congestive heart failure
      (odds ratio, 3.65; 95% confidence interval, 1.18-11.26), coagulopathy (odds
      ratio, 3.58; 95% confidence interval, 1.88-6.81), and electrolyte abnormalities
      (odds ratio, 3.28; 95% confidence interval, 2.14-5.02). CONCLUSION: During the
      examined 10-year period, both the incidence of nonosteoporotic sacral fractures
      and the surgical treatment of these lesions increased in the United States.
      Between 2002 and 2011, although patient comorbidity increased, in-hospital
      complication rates remained stable and length of stay significantly decreased
      over time. LEVEL OF EVIDENCE: 4.

PMID- 24875963
TI  - Is there a relationship between thoracic dimensions and pulmonary function in
      early-onset scoliosis?
AB  - STUDY DESIGN: Cross-sectional retrospective analysis. OBJECTIVE: To examine the
      degree of correlation between thoracic dimension outcome measures and pulmonary
      function in early-onset scoliosis (EOS). SUMMARY OF BACKGROUND DATA: Change in
      thoracic dimension (TD) measurements and spine length are commonly reported
      outcome measures after treatment for EOS. Although ultimately improving or
      maintaining pulmonary function is the goal of EOS treatment strategies, it is
      unclear whether commonly reported 2-dimensional TD measurements represent good
      predictors of pulmonary function. METHODS: A cross-sectional analysis of patients
      including all diagnoses obtained from 2 EOS databases containing TD measurements
      and pulmonary function data was performed. Relationships between individual TD
      measurements and pulmonary function measurements were assessed using the Pearson
      correlation analysis. TD measurements (pelvic inlet width, T1-T12 height, T1-S1
      height, and coronal chest width) and standard pulmonary function measurements
      were compared. TD percentiles normalized for pelvic inlet width were also
      calculated and correlated with pulmonary function measurement percentiles.
      Univariate and multivariate linear regression analyses determined whether TD
      measurements could predict pulmonary function. RESULTS: There were 121 patients
      (65 females, 56 males) in the study. Mean age at evaluation was 9.3 years (range,
      2.7-18.1 yr). T1-T12 height, T1-S1 height, maximal chest width, and pelvic inlet
      width were all significantly correlated with forced air volume expelled in 1
      second, total forced air volume, and total lung capacity (correlation
      coefficients [r] 0.33-0.61; all P<0.001). T1-T12 predicted percentile (normalized
      for pelvic width) was significantly correlated with forced air volume expelled in
      1 second and total forced air volume predicted percentiles (r=0.32, P<0.001 and
      r=0.27, P=0.004, respectively). Regression analysis determined that T1-T12
      percentile was a significant predictor of forced air volume expelled in 1 second
      percentile and total forced air volume percentiles. Regression analysis found no
      predictive factors of total lung capacity percentile. CONCLUSION: Traditional 2
      dimensional TD measurements (T1-T12 height) used to measure outcomes in EOS can
      be used as weak predictors of pulmonary function outcome. However, better outcome
      measures need to be developed, such as 3-dimensional and dynamic measurements.
      LEVEL OF EVIDENCE: 3.

PMID- 24875964
TI  - Preoperative pain neuroscience education for lumbar radiculopathy: a multicenter
      randomized controlled trial with 1-year follow-up.
AB  - STUDY DESIGN: Multicenter, randomized, controlled trial on preoperative pain
      neuroscience education (NE) for lumbar radiculopathy. OBJECTIVE: To determine if
      the addition of NE to usual preoperative education would result in superior
      outcomes with regard to pain, function, surgical experience, and health care
      utilization postsurgery. SUMMARY OF BACKGROUND DATA: One in 4 patients after
      lumbar surgery (LS) for radiculopathy experience persistent pain and disability,
      which is nonresponsive to perioperative treatments. NE focusing on the
      neurophysiology of pain has been shown to decrease pain and disability in
      populations with chronic low back pain. METHODS: Eligible patients scheduled for
      LS for radiculopathy were randomized to receive either preoperative usual care
      (UC) or a combination of UC plus 1 session of NE delivered by a physical
      therapist (verbal one-on-one format) and a NE booklet. Sixty-seven patients
      completed the following outcomes prior to LS (baseline), and 1, 3, 6, and 12
      months after LS: low back pain (numeric rating scale), leg pain (numeric rating
      scale), function (Oswestry Disability Index), various beliefs and experiences
      related to LS (10-item survey with Likert scale responses), and postoperative
      utilization of health care (utilization of health care questionnaire). RESULTS:
      At 1-year follow-up, there were no statistical differences between the
      experimental and control groups with regard to primary outcome measure of low
      back pain (P = 0.183), leg pain (P = 0.075), and function (P = 0.365). In a
      majority of the categories regarding surgical experience, the NE group scored
      significantly better: better prepared for LS (P = 0.001); preoperative session
      preparing them for LS (P < 0.001) and LS meeting their expectations (P = 0.021).
      Health care utilization post-LS also favored the NE group (P = 0.007) resulting
      in 45% less health care expenditure compared with the control group in the 1-year
      follow-up period. CONCLUSION: NE resulted in significant behavior change. Despite
      a similar pain and functional trajectory during the 1-year trial, patients with
      LS who received NE viewed their surgical experience more favorably and used less
      health care facility in the form of medical tests and treatments. LEVEL OF
      EVIDENCE: 2.

PMID- 24875965
TI  - Secular changes of spinal canal dimensions in Western Switzerland: a narrowing
      epidemic?
AB  - STUDY DESIGN: Computed tomography-based anatomical study. OBJECTIVE: To study the
      secular changes in lumbar spinal canal dimensions. SUMMARY OF BACKGROUND DATA:
      Development of symptomatic lumbar spinal stenosis, among other factors, is
      related to the dimensions of the bony canal. The canal reaches its adult size
      early on in life. Several factors, including protein intake, may influence its
      final dimensions. As with increases in human stature from improvements of
      socioeconomic conditions, we hypothesized that adult bony canal size has also
      grown larger in recent generations. METHODS: This study analyzes computed
      tomographic reconstructions from 184 subjects performed for either trauma (n =
      81) or abdominal pathologies (n = 103) and born either between 1940 and 1949 (n =
      88) or 1970 and 1979 (n = 96). The cross-sectional area of the bony canal was
      digitally measured at the level of the pedicle (i.e., at a level not influenced
      by degenerative changes) for each lumbar vertebra. Intra- and interobserver
      reliability was assessed. RESULTS: Intra- and interobserver measurement
      reliability were excellent (interclass correlation coefficient = 0.87) and good
      (interclass correlation coefficient = 0.61), respectively. Contrary to our
      hypothesis, the 1940-1949 generation patient group exhibited larger lumbar canals
      at all levels as compared with the 1970-1979 group. Statistically this difference
      was highly significant (P < 0.001) and particularly pronounced in the trauma
      subgroup. CONCLUSION: Given that human stature evolution has stabilized and adult
      height is established during the first 2 years of long bone growth, it is
      possible that antenatal factors are responsible for this surprising finding.
      Maternal smoking and age may be possible explanations. This finding may have
      significant implications. An increasing number of patients may emerge with lumbar
      spinal stenosis as degenerative changes develop, putting a strain on health
      resources. Further studies in different population groups and countries will be
      important to further confirm this trend. LEVEL OF EVIDENCE: 3.

PMID- 24875966
TI  - An intraosseous lipoma of the calcaneus: a case report.
AB  - Intraosseous lipomas are one of the rarest bone tumors found in the body. The
      incidence has been reported to be <0.1% of all primary bone tumors. The
      differential diagnoses of an intraosseous lipoma in the calcaneus include plantar
      fasciitis, retrocalcaneal bursitis, gout, stress fracture, unicameral bone cyst,
      aneurysmal bone cyst, osteoblastoma, enchondroma, chondromyxoid fibroma,
      nonossifying fibroma, giant cell tumor, chondroblastoma, fibrous dysplasia, and
      chondrosarcoma. It has been reported that 60% to 70% of patients with an
      intraosseous lipoma present with symptoms. This article describes a case of a
      pathologic fracture secondary to a large intraosseous lipoma, the surgical
      treatments, and the subsequent resolution of symptoms. The purpose of our report
      was 3-fold: (1) to increase awareness of intraosseous lipomas and their potential
      to cause pathologic fractures in the calcaneus; (2) to suggest a possible
      treatment protocol for intraosseous lipomas in the calcaneus; and (3) to describe
      a rare case of an intraosseous lipoma of the calcaneus not located exclusively in
      the neutral triangle. 

PMID- 24875967
TI  - Ankle syndesmotic fixation using two screws: risk of injury to the perforating
      branch of the peroneal artery.
AB  - Trans-syndesmotic screws are commonly used to repair syndesmosis ruptures and
      stabilize the ankle joint. Just as with any surgery, the neurovascular structures
      can be compromised, causing complications. We evaluated the position of the
      perforating branch of the peroneal artery to define the risk of arterial
      compromise during placement of 2 trans-syndesmotic screws. In 37 cadaveric
      specimens, 2 trans-syndesmotic screws were inserted 2 and 4 cm proximal to the
      ankle joint. The distances between the perforating branch of the peroneal artery
      and the screws and the other anatomic landmarks were measured. Significant
      differences were calculated between the male and female limbs, and regression
      analysis was used to determine the significant associations between the tibial
      length and screw location. The perforating branch of the peroneal artery passed
      through the interosseous membrane 3.42 +/- 0.6 cm proximal to the tibial plafond.
      The artery was located up to 4 mm from the superior and inferior screws 51.4% and
      10.8% of the time, respectively. A greater percentage of male specimens displayed
      close proximity between the artery and the superior screw, and the distance of
      the artery from the distal fibula was statistically significant compared with the
      distance in the female specimens. Regression analysis revealed that the greater
      the tibial length, the closer the superior screw was to the artery, with a
      negative correlation discovered for the inferior screw. We concluded that
      superior screw placement increased the risk of injuring the perforating branch of
      the peroneal artery injury, and the likelihood of injuring the artery with the
      inferior screw increased as the length of the tibia decreased.

PMID- 24875968
TI  - Pregabalin reduces opioid consumption and improves outcome in chronic pain
      patients undergoing total knee arthroplasty.
AB  - INTRODUCTION: Recently, multimodal pain control has been used to manage
      postoperative pain in patients undergoing total knee arthroplasty (TKA). This
      approach combines numerous modalities, such as opioids, nonsteroidal anti
      inflammatory drugs, local anesthetics, and acetaminophen, in an effort to reduce
      overall opioid consumption and also to provide better pain control.
      Gabapentinoids are a class of drugs that have been used as part of multimodal
      approach, and may be effective in patients who are previous users of chronic pain
      medication. The hypothesis of this study was that the addition of pregabalin
      reduces opioid consumption and/or improves pain after TKA, even in patients who
      are previous users of chronic pain medications. METHODS: Using a prospectively
      collected database, 262 consecutive patients undergoing primary TKA between
      December 2011 and April 2012 were identified who received multimodal analgesia
      after surgery that included pregabalin. Using the same database, these patients
      were compared with 268 patients undergoing TKA from January to December 2010 who
      also received multimodal analgesia but were not given pregabalin. The clinical
      records of these patients were reviewed in detail to determine the incidence and
      nature of postoperative complications, opioid consumption, and visual analog
      scale (VAS) pain scores. RESULTS: The incidence of respiratory, renal, and
      hemodynamic complications was significantly lower in the patients who received
      pregabalin. Gastrointestinal complications, which included nausea, were not
      significantly different between the groups. Patients receiving pregabalin had a
      lower average opioid consumption, and their minimum and maximum levels of opioid
      consumption were also reduced. Previous users of chronic pain medications had
      higher VAS scores but the same opioid consumption compared with those who were
      not previous users of chronic pain medications. No difference was seen in the
      maximum VAS scores between patients who received pregabalin and those who did
      not. CONCLUSION: Pregabalin in the context of multimodal pain management may be
      associated with reduced opioid consumption and other medical complications in
      patients undergoing TKA, including previous users of chronic pain medications.

PMID- 24875969
TI  - Nonprescription pain medication use in collegiate athletes: a comparison of
      samples.
AB  - BACKGROUND: Despite recent research, nonprescription pain medication use among
      collegiate athletes across all divisions of the National Collegiate Athletic
      Association (NCAA) is still not well understood. HYPOTHESIS: Non-Division I-A
      NCAA athletes have a different usage pattern of nonprescription pain medication
      than NCAA Division I-A football athletes. METHODS: A modified version of a
      nonprescription medication usage survey that had been used with Division I-A
      football athletes was distributed to Division II and Division III athletes during
      pre-participation exams. The statistics were analyzed by calculating the z-ratio
      for the significance of the difference between 2 independent proportions.
      RESULTS: A total of 198 athletes from 16 different sports were surveyed. It was
      found that 62% of athletes used nonprescription medications for sports-related
      pain, which was significantly lower than previous findings for Division I-A
      football athletes: 12% reported taking more than the recommended dose; 1.5%
      reported taking nonprescription pain medication for > 10 consecutive days; and
      38% reported that they read the label the first time they took a new
      nonprescription pain medication. These results, when compared with findings on
      Division I-A football athletes, demonstrated that Division II and III athletes
      are less likely to take more than the recommended dose of nonprescription pain
      medications and are less likely to use the medications for > 10 consecutive days
      characteristics that are used to define misuse. Similar results were found when
      comparing Division I-A football athletes with non-Division I-A football athletes.
      CONCLUSIONS: Athletes from NCAA Division II and Division III sports appear to use
      nonprescription pain medication for sports-related pain less often and have lower
      rates of misuse than do Division I-A football athletes. Division I-A football
      athletes may be more likely to misuse nonprescription pain medication than non
      Division I-A athletes. Special attention should be paid to this population to
      help reduce adverse event risks.

PMID- 24875970
TI  - The effects of platelet-rich plasma in the treatment of large-joint
      osteoarthritis: a systematic review.
AB  - CONTEXT: Osteoarthritis (OA) is a common and costly condition with both operative
      and nonoperative treatments available. Platelet-rich plasma (PRP) is emerging as
      a treatment option for a variety of musculoskeletal pathologies, including OA.
      OBJECTIVE: To evaluate the effectiveness of intra-articular PRP injection in the
      treatment of large-joint OA. DATA SOURCES: PubMed, Web of Knowledge, Scopus, and
      the Cochrane Database were searched. The references of all articles that met the
      inclusion criteria were manually searched for additional articles. STUDY
      SELECTION: English studies that enrolled human participants were included, with
      level of evidence I to IV. RESULTS: Thirteen articles met the inclusion criteria:
      12 focused on knee OA, and 1 on hip OA. All studies showed statistically
      significant improvement in patient outcome scores with PRP. Platelet-rich plasma
      has a statistically significant benefit in knee OA when compared with hyaluronic
      acid. The benefit from PRP appears to last between 6 and 12 months. CONCLUSION:
      Platelet-rich plasma may be an effective treatment for knee OA. However, because
      of the low level of evidence, small sample sizes, and wide variability in
      treatment, no definitive recommendations can be made at this time.

PMID- 24875971
TI  - Evaluation of hip pain in young adults.
AB  - Hip pain is a common complaint in the young, athletic patient population.
      Primary, intra-articular sources of hip pain are becoming increasingly recognized
      by primary care providers and sports medicine specialists. Prior to deciding
      among the various treatment options for the many sources of hip pain in the
      athletic patient population, the clinician must be able to recognize and
      accurately diagnose the underlying pathology. Advances in imaging modalities and
      our understanding of the pathophysiology have improved our ability to accurately
      understand and diagnose the source of hip pain in this patient population. This
      review presents a comprehensive strategy for the workup and diagnosis of young,
      athletic patients presenting with hip pain, and provides the sports medicine
      specialist with the tools to correlate the patient's history, physical
      examination, and imaging findings and to treat these challenging patients. 

PMID- 24875972
TI  - Effect of kinesiology taping on pain in individuals with musculoskeletal
      injuries: systematic review and meta-analysis.
AB  - Kinesiology tape, an elastic tape used by sports medicine clinicians to enhance
      sports performance in athletes, is purported to facilitate a reduction in pain
      during physical activity in individuals with orthopedic injuries, but high
      quality literature on this topic remains scarce. The purpose of this meta
      analysis is to critically examine and review the existing literature to evaluate
      the effect of kinesiology tape application on pain in individuals with
      musculoskeletal injury. English-language publications from 2003 to 2013 were
      surveyed by searching SPORTDiscus, Scopus, ScienceDirect, CINAHL, Cochrane
      Library, PubMed, and PEDro databases using the terms kinesio tap*, kinesiology
      tap*, kinesiotap*, and pain. Thirteen articles investigating the effects of
      kinesiology tape application on pain with at least level II evidence were
      selected. The combined results of this meta-analysis indicate that kinesiology
      tape may have limited potential to reduce pain in individuals with
      musculoskeletal injury; however, depending on the conditions, the reduction in
      pain may not be clinically meaningful. Kinesiology tape application did not
      reduce specific pain measures related to musculoskeletal injury above and beyond
      other modalities compared in the context of included articles. We suggest that
      kinesiology tape may be used in conjunction with or in place of more traditional
      therapies, and further research that employs controlled measures compared with
      kinesiology tape is needed to evaluate efficacy.

PMID- 24875973
TI  - Evidence-based approach of treatment options for postoperative knee pain.
AB  - Optimal pain management is critical after knee surgery to avoid adverse events
      and to improve surgical outcomes. Pain may affect surgical outcomes by
      contributing to limitations in range of motion, strength, and functional
      recovery. The causes of postoperative pain are multifactorial; therefore, an
      appropriate pain management strategy must take into account preoperative,
      intraoperative, and postoperative factors to create a comprehensive and
      individualized plan for the patient. Preoperative assessment includes management
      of patient expectations, recognition of conditions and early counseling for high
      risk patients (ie, opioid dependence, psychiatric comorbidities), and use of
      preemptive analgesia techniques (ie, preoperative IV medications, peripheral
      nerve blocks, incisional field blocks). Intraoperative strategies include
      meticulous surgical technique, limiting the use of tourniquets (ie, duration and
      pressure), and using preventive analgesia methods (ie, postoperative field block,
      continuous nerve catheters, intra-articular injection). Postoperative analgesia
      may be facilitated by cryotherapy, early mobilization, bracing, and
      rehabilitation. Certain modalities (ie, continuous passive motion devices,
      transcutaneous electrical nerve stimulation units, iontophoresis) may be
      important adjuncts in the perioperative period as well. There may be an evolving
      role for alternative medicine strategies. Early recognition and treatment of
      exaggerated postoperative pain responses may mitigate the effects of complex
      regional pain syndrome or the development of chronic pain. 

PMID- 24875974
TI  - Low proportion of high school senior athletes receiving recommended
      immunizations.
AB  - BACKGROUND: The preparticipation physical evaluation (PPE) often serves as the
      only preventive health care visit for athletes, but immunization status is not
      uniformly addressed in such visits. Thus, athletes may not be receiving
      recommended immunizations. Our aim was to determine the proportion of high school
      senior athletes who received all recommended immunizations. HYPOTHESIS: Our
      hypothesis was that females would be less likely than males to receive all
      recommended immunizations given suboptimal human papillomavirus (HPV) vaccine
      uptake. METHODS: We conducted a cross-sectional survey evaluation of the
      immunization status of high school senior athletes in Davidson County, TN. The
      primary composite outcome was receipt of recommended immunizations for tetanus,
      meningococcal, and seasonal influenza. For females, the primary outcome also
      included completion of the HPV series. RESULTS: A total of 162 participants, 104
      males and 58 females, were included. More males than females received all
      recommended immunizations (15.4% vs 3.5%; P = 0.02). When HPV immunization was
      excluded from the composite outcome, there was no difference in the proportion of
      males and females who received all recommended immunizations (15.4% vs 15.5%; P =
      0.98). The odds of receiving all recommended immunizations was 0.14 (95% CI, 0.03
      0.72) for females compared with males when adjusted for covariates. Athletes seen
      at retail-based clinics for their PPE were less likely to receive all recommended
      immunizations compared with athletes seen in primary care (OR, 0.13; 95% CI, 0.02
      0.69). CONCLUSIONS: Only 1 in 6 high school senior athletes received the
      recommended tetanus, meningococcal, and influenza immunizations. A lower
      proportion of females, only 1 in 28, received all recommended immunizations due
      to the HPV series. Policy changes requiring a review of immunizations at the PPE
      would benefit many high school athletes.

PMID- 24875975
TI  - Muscle activation in young men during a lower limb aquatic resistance exercise
      with different devices.
AB  - Little research has been reported on the effects of using different devices with
      resistance exercises in a water environment. This study compared muscular
      activation of lower extremity and core muscles during leg adduction performed at
      maximum velocity with drag and floating devices of different sizes. A total of 24
      young men (mean age 23.20 +/- 1.18 years) performed 3 repetitions of leg
      adduction at maximum velocity using 4 different devices (ie, large/small and
      drag/floating). The maximum amplitude of the electromyographic root mean square
      of the adductor longus, rectus abdominis, external oblique on the dominant side,
      external oblique on the nondominant side, and erector lumbar spinae were
      recorded. Electromyographic signals were normalized to the maximum voluntary
      isometric contraction (MVIC). Unexpectedly, no significant (P > 0.05) differences
      were found in the neuromuscular responses among the different devices used; the
      average activation of agonist muscle adequate for neuromuscular conditioning was
      40.95% of MVIC. In addition, external oblique activation is greater on the
      contralateral side to stabilize the body (average, 151.74%; P < 0.05). Therefore,
      if maximum muscle activation is required, the kind of device is not relevant.
      Thus, the choice should be based on economic factors. 

PMID- 24875976
TI  - A brief review and clinical application of heart rate variability biofeedback in
      sports, exercise, and rehabilitation medicine.
AB  - CONTEXT: An important component of the effective management of chronic
      noncommunicable disease is the assessment and management of psychosocial stress.
      The measurement and modulation of heart rate variability (HRV) may be valuable in
      this regard. OBJECTIVE: To describe the measurement and physiological control of
      HRV; to describe the impact of psychosocial stress on cardiovascular disease,
      metabolic syndrome, and chronic respiratory disease, and the relationship between
      these diseases and changes in HRV; and to describe the influence of biofeedback
      and exercise on HRV and the use of HRV biofeedback in the management of chronic
      disease. DATA SOURCES AND STUDY SELECTION: The PubMed, Medline, and Embase
      databases were searched (up to August 2013). Additional articles were obtained
      from the reference lists of relevant articles and reviews. Articles were
      individually selected for further review based on the quality and focus of the
      study, and the population studied. RESULTS: Heart rate variability is reduced in
      stress and in many chronic diseases, and may even predict the development and
      prognosis of some diseases. Heart rate variability can be increased with both
      exercise and biofeedback. Although the research on the effect of exercise is
      conflicting, there is evidence that aerobic training may increase HRV and cardiac
      vagal tone both in healthy individuals and in patients with disease. Heart rate
      variability biofeedback is also an effective method of increasing HRV and cardiac
      vagal tone, and has been shown to decrease stress and reduce the morbidity and
      mortality of disease. CONCLUSION: The assessment and management of psychosocial
      stress is a challenging but important component of effective comprehensive
      lifestyle interventions for the management of noncommunicable disease. It is,
      therefore, important for the sports and exercise physician to have an
      understanding of the therapeutic use of HRV modulation, both in the reduction of
      stress and in the management of chronic disease.

PMID- 24875977
TI  - Exercise, the athlete's heart, and sudden cardiac death.
AB  - Physical activity is a potent therapy for both the prevention and treatment of
      cardiovascular disease. Exercise appears to most benefit people who are the least
      active. There is some evidence to suggest that a curvilinear relationship exists
      between exercise and survival, whereby beyond an optimal level of fitness, the
      principle of diminishing returns applies. Indeed, some go further in suggesting
      that there is evidence that extreme athletic training may be harmful in some
      individuals. The incidence of sudden cardiac death in athletes is greater than in
      matched, nonathletic counterparts, and this finding is driven by the provocation
      of an underlying cardiac abnormality by strenuous exertion. The task of detecting
      pathological myocardial substrate in athletes is made difficult by physiological
      adaptations to exercise that can mimic the appearance of cardiomyopathies and ion
      channelopathies in some individuals. This article details the clinical evaluation
      of the athlete with reference limits for cardiac physiological remodeling and
      discusses the diagnostic dilemmas that arise. 

PMID- 24875978
TI  - Functional results following surgical repair of simultaneous bilateral quadriceps
      tendon ruptures.
AB  - BACKGROUND: Unilateral quadriceps tendon ruptures are common conditions treated
      by orthopedic surgeons. There is a paucity of information concerning functional
      outcomes in bilateral tendon ruptures. The aim of this study is to assess a
      series of 5 cases with simultaneous quadriceps tendon ruptures that underwent
      acute surgical repair with the purpose of identifying the functional outcomes as
      compared with unilateral injuries. We hypothesize that patients with bilateral
      quadriceps tendon ruptures have worse functional outcomes than patients with
      unilateral ruptures. METHODS: Five cases of bilateral quadriceps tendon ruptures
      were identified. All patients underwent acute surgical extensor tendon repair
      employing a 3-patellar hole and a locked, running, nonabsorbable suture technique
      followed by a 6-week period of immobilization and bracing for 10 to 12 weeks.
      Mechanism of injury, medical history, social history, operative report, and
      postoperative exam were recorded with a minimum 1-year follow-up. In addition,
      each patient completed a subjective International Knee Documentation Committee
      (IKDC) score at 18 months. Five patients with unilateral injuries and with
      similar medical history were included as age-matched controls. RESULTS: The mean
      age for the bilateral group was 54.8 years (range, 44-68 years). Mean
      postoperative knee flexion was 129 degrees and all patients had active, resisted
      knee extension. Only 1 patient had a medical comorbidity (diabetes mellitus). The
      mean IKDC score (mean follow-up, 25.4 months; range, 22-29 months) was 71.9
      (range, 34.4 to 91.6), whereas the age-matched control group had a mean IKDC
      score of 88.3 (P = 0.23). There was no statistical significance between the 2
      groups with regard to range of motion (P = 0.24), IKDC score, and return to
      activity (P = 0.29). CONCLUSION: Patients with early surgical repair of
      bilateral, simultaneous extensor mechanism ruptures exhibit adequate recovery and
      return to a high level of function. Our patients were younger than those reported
      in the literature and had minimal comorbidities. The IKDC scores reflected good
      outcomes in the bilateral rupture group, albeit lower than in the unilateral
      group.

PMID- 24875979
TI  - Diet and exercise interventions following coronary artery bypass graft surgery: a
      review and call to action.
AB  - Coronary artery bypass graft (CABG) surgery has been used for the treatment of
      coronary artery disease (CAD) for approximately 50 years, and has been performed
      on millions of people globally. However, little is known about the impact of diet
      and exercise on long-term outcomes of patients who have undergone CABG surgery.
      Although clinical practice guidelines on the management of this patient
      population have been available for approximately 2 decades, evidence regarding
      secondary prevention behavioral interventions, lifestyle modifications and self
      management to slow the progressive decline of CAD, reduce cardiac
      hospitalizations, and prevent reoperation remains virtually absent from the
      literature. Diet and exercise are modifiable factors that affect secondary CAD
      risk. This article reviews the relevant current literature on long-term diet and
      exercise outcomes in patients who underwent CABG. The limited available
      literature shows the positive impacts of exercise on psychosocial well-being and
      physical fitness. Current evidence indicates diet and exercise interventions are
      effective in the short-term, but effects fade over time. Potential age and sex
      differences were found across the reviewed studies; however, further research is
      needed with more rigorous designs to replicate and confirm findings, and to
      define optimal management regimens and cost-effective prevention strategies. 

PMID- 24875980
TI  - Drug abuse relapse rates linked to level of education: can we repair
      hypodopaminergic-induced cognitive decline with nutrient therapy?
AB  - It is well known that athletes and other individuals who have suffered painful
      injuries are at increased risk for all reward deficiency syndrome (RDS)
      behaviors, including substance use disorder (SUD). Comparing patient demographics
      and relapse rates in chemical dependence programs is pertinent because
      demographics may affect outcomes. Increased risk for relapse and lower academic
      achievement were found to have a significant association in recent outcome data
      from a holistic treatment center (HTC) located in North Miami Beach, FL. Relapse
      outcomes from the Drug Addiction Treatment Outcome Study (DATOS; n = 1738) and
      HTC (n = 224) were compared for a 12-month period. Post-discharge relapse was
      reported by 26% of HTC patients and 58% of patients in DATOS. When broken out by
      education level-less than high school, high school diploma, college degree, and
      graduate degree-HTC patient relapse was 50%, 36%, 33%, and 16%, respectively, and
      demonstrated an inverse linear association (F = 5.702; P = 0.017). Looking at
      DATOS patient relapse rates broken down by educational grades/years completed,
      patients who attended school between 7th grade and 4 years of college also
      demonstrated an inverse linear association (F = 5.563; P = 0.018). Additionally,
      the lowest performers, patients who reported their academic performance as "not
      so good," had the highest relapse (F = 4.226; P = 0.04). Albeit certain
      limitations, compared with DATOS patients, HTC patients produced significantly
      larger net differences in relapse rates (X 2 = 84.09; P = 0.0001), suggesting
      that other variables, such as the treatment model may also affect patient
      relapse. Our results implicate the use of vitamin and mineral supplements coupled
      with a well-researched natural dopamine agonist nutrient therapy; both have been
      shown to improve cognition and behavior, and thus academic achievement. That
      relapse is highest among addicts who have less education and who report lower
      grades is a factor that can be useful when considering treatment type and
      controlled for when comparing treatment outcomes. 

PMID- 24875982
TI  - Sports reporting: a comprehensive review of the medical literature regarding
      North American professional sports.
AB  - BACKGROUND: The increased physical demands of professional athletes predispose
      this patient population to a unique set of injuries typically not seen in the
      general population. This systematic literature review investigates the nature of
      injury reporting (both orthopedic and nonorthopedic conditions) in the medical
      literature of professional athletes in the National Football League (NFL), Major
      League Baseball (MLB), the National Basketball Association (NBA), and the
      National Hockey League (NHL). Rigorous reporting of sports injuries helps
      clinicians better understand disease mechanisms relevant to specific sports.
      HYPOTHESIS: The nature of injury reporting will differ within each professional
      sport and reflect the anatomic emphasis of each sport. METHODS: An electronic
      literature search of all publications addressing injuries and medical conditions
      among professional athletes in the NFL, MLB, NBA, and NHL was conducted using the
      Pubmed/Medline, Scopus, and Embase databases through January 2013. Retrieved
      publications were categorized by journal type, medical type, and area of focus.
      RESULTS: A total of 536 publications met all inclusion criteria. There were a
      higher number of articles regarding the NFL (n = 211) and MLB (n = 216) when
      compared with the NBA (n = 34) or NHL (n = 75). The NFL had significantly more
      articles addressing nonorthopedic injuries/medical issues than were found with
      the MLB, NBA, or NHL (109 vs 75, 14, 41, respectively). Both the NFL (33 of 109,
      30%) and NHL (6 of 41, 15%) had a relatively high percentage of articles
      regarding concussions/neurology, and MLB had a relatively high percentage of
      articles dedicated to vascular medicine (13 of 65, 20%). The proportion of
      publications dedicated to the knee/lower leg were highest in the NFL (29 of 102,
      28%) and NBA (9 of 20, 45%), those dedicated to the shoulder/elbow were highest
      in MLB (113 of 151, 75%), and those dedicated to the hip/pelvis were highest in
      the NHL (16 of 34, 47%). CONCLUSIONS: The number and type of publications vary
      among the 4 professional sports leagues, and generally reflect the nature of the
      sport being played.

PMID- 24875983
TI  - Nanomechanical and optical properties of yttrium thin films by magnetron
      sputtering.
AB  - This Letter reports on nanomechanical and optical properties of yttrium thin
      films deposited on an Si (100) wafer. Elemental depth profiling by a secondary
      ion mass spectrometer revealed absence of formation of yttrium hydride, both on
      the surface and beneath. The optical properties were investigated by
      spectroscopic ellipsometry, and the refractive indices extracted after suitable
      modeling were found to be 2.51 at 546 nm. Hardness and elastic modulus of these
      films were found to be 7 and 142 GPa, respectively. These studies indicate that
      yttrium thin films are suitable for x-ray mirrors, photocathode emitters in e
      beam lithography, electron microscopes, and free-electron lasers. 

PMID- 24875981
TI  - Epidemiology of basketball, soccer, and volleyball injuries in middle-school
      female athletes.
AB  - BACKGROUND: An estimated 30 to 40 million school children participate in sports
      in the United States; 34% of middle-school participants become injured and seek
      medical treatment at an annual cost close to $2 billion. The purpose of the
      current study was to evaluate the injury incidence and rates in female athletes
      in the middle-school setting during the course of 3 seasons. METHODS: Female
      basketball, soccer, and volleyball players were recruited from a single county
      public school district in Kentucky consisting of 5 middle schools. A total of 268
      female athletes (162 basketball, 26 soccer, and 80 volleyball) participated.
      Athletes were monitored for sports-related injury and number of athlete exposures
      (AEs) by an athletic trainer. Injury rates were calculated for specific types of
      injuries within each sport. Injury rates for games and practices were also
      calculated and compared for each sport. RESULTS: A total of 134 injuries were
      recorded during the 3 sport seasons. The knee was the most commonly injured body
      part (99 injuries [73.9%]), of which patellofemoral dysfunction (31.3%), Osgood
      Schlatter disease (10.4%), and Sinding-Larsen-Johansson/patella tendinosis (9%)
      had the greatest incidence. The ankle was the second most commonly injured body
      part, accounting for 16.4% of all injuries. The overall rates of injury by sport
      were as follows: soccer, 6.66 per 1000 AEs; volleyball, 3.68 per 1000 AEs; and
      basketball, 2.86 per 1000 AEs. CONCLUSIONS: Female middle-school athletes
      displayed comparable injury patterns to those seen in their high-school
      counterparts. Future work is warranted to determine the potential for improved
      outcomes in female middle-school athletes with access to athletic training
      services. CLINICAL RELEVANCE: As the participation levels and number of injuries
      continue to rise, middle-school athletes demonstrate an increasing need for
      medical services provided by a certified athletic trainer.

PMID- 24875984
TI  - Er/Tm:fiber laser system for coherent Raman microscopy.
AB  - We present a novel architecture for a fiber-based hybrid laser system for
      coherent Raman microscopy, combining an amplified Er:fiber femtosecond oscillator
      with a Tm:fiber amplifier boosting the power of the 2-MUm portion of a
      supercontinuum up to 300 mW. This is enough to obtain, by means of nonlinear
      spectral compression, sub-20-cm(-1) wide pump and Stokes pulses with 2500-3300 
      cm(-1) frequency detuning and average power at the 100-mW level. Application of
      this system to stimulated Raman scattering microscopy is discussed.

PMID- 24875985
TI  - Dynamic control of wideband slow wave in graphene based waveguides.
AB  - Enlarged group index has been reported previously when surface plasmons propagate
      through the graphene sheet, yet a clear slow wave performance in graphene has not
      been explored. We proposed and numerically analyzed here for the first time to
      the best of our knowledge an extremely wideband slow surface wave in a graphene
      based grating waveguide. The strongly delayed wave (120<n(g)<167) with extremely
      large bandwidth (2.7 THz>Deltaf>0.7 THz) can be dynamically controlled via the
      gate-voltage dependent optical properties of graphene. Our results suggest that
      graphene may be a very promising slow light medium, promoting future slow light
      devices based on graphene.

PMID- 24875986
TI  - Observation of two-photon fluorescence for Rhodamine 6G in microbubble
      resonators.
AB  - We report an observation of multi-photon excitation of organic chromophores in
      microbubble whispering gallery mode resonators. High-Q microbubble resonators
      were formed by heating a pressurized fused silica capillary to form a hollow
      bubble that was then filled with liquid. In this work, the microbubble was filled
      with a solution of Rhodamine 6G dye. The resonator and dye were excited by
      evanescently coupling continuous wave (CW) light from a 980 nm laser diode using
      a tapered optical fiber. The two-photon fluorescence of the dye can be seen with
      pump powers as low as 700 MUW. 

PMID- 24875987
TI  - Molecular specificity in photoacoustic microscopy by time-resolved transient
      absorption.
AB  - We have recently harnessed transient absorption, a resonant two-photon process,
      for ultrahigh resolution photoacoustic microscopy, achieving nearly an order of
      magnitude improvement in axial resolution. The axial resolution is optically
      constrained due to the two-photon process unlike traditional photoacoustic
      microscopy where the axial resolution is inversely proportional to the frequency
      bandwidth of the detector. As a resonant process, the arrival time of the two
      photons need not be instantaneous. Systematically recording the signal as a
      function of the delay between two pulses will result in the measurement of an
      exponential decay whose time constant is related to the molecular dynamics. This
      time constant, analogous to the fluorescence lifetime, but encompassing
      nonradiative decay as well, can be used to differentiate between molecular
      systems with overlapping absorption spectra. This is frequently the situation for
      closely related yet distinct molecules such as redox pairs. In order to enable
      the measure of the exponential decay, we have reconfigured our transient
      absorption ultrasonic microscopy (TAUM) system to incorporate two laser sources
      with precisely controlled pulse trains. The system was tested by measuring
      Rhodamine 6G, an efficient laser dye where the molecular dynamics are dominated
      by the fluorescence pathway. As expected, the measured exponential time constant
      or ground state recovery time, 3.3+/-0.7  ns, was similar to the well-known
      fluorescence lifetime, 4.11+/-0.05  ns. Oxy- and deoxy-hemoglobin are the
      quintessential pair whose relative concentration is related to the local blood
      oxygen saturation. We have measured the ground state recovery times of these two
      species in fully oxygenated and deoxygenated bovine whole blood to be 3.7+/-0.8 
      ns and 7.9+/-1.0  ns, respectively. Hence, even very closely related pairs of
      molecules may be differentiated with this technique. 

PMID- 24875988
TI  - CMOS-compatible 75 mW erbium-doped distributed feedback laser.
AB  - On-chip, high-power, erbium-doped distributed feedback lasers are demonstrated in
      a CMOS-compatible fabrication flow. The laser cavities consist of silicon nitride
      waveguide and grating features, defined by wafer-scale immersion lithography and
      an erbium-doped aluminum oxide layer deposited as the final step in the
      fabrication process. The large mode size lasers demonstrate single-mode
      continuous wave operation with a maximum output power of 75 mW without any
      thermal damage. The laser output power does not saturate at high pump intensities
      and is, therefore, capable of delivering even higher on-chip signals if a
      stronger pump is utilized. The amplitude noise of the laser is investigated and
      the laser is shown to be stable and free from self-pulsing when the pump power is
      sufficiently above threshold. 

PMID- 24875989
TI  - Stokes vector direct detection for short-reach optical communication.
AB  - We propose the Stokes vector direct detection (SV-DD) scheme which simultaneously
      achieves receiver phase diversity and the cancellation of photodetection
      nonlinearity. An 80  Gb/s single-polarization modulated SV-DD signal is
      successfully received after 160 km SSMF transmission with 11.64  bit/s/Hz
      electrical spectrum efficiency.

PMID- 24875990
TI  - Crystal orientation dependence of femtosecond laser-induced periodic surface
      structure on (100) silicon.
AB  - It is widely believed that laser-induced periodic surface structures (LIPSS) are
      independent of material crystal structures. This Letter reports an abnormal
      phenomenon of strong dependence of the anisotropic formation of periodic ripples
      on crystal orientation, when Si (100) is processed by a linearly polarized
      femtosecond laser (800 nm, 50 fs, 1 kHz). LIPSS formation sensitivity with a pi/2
      modulation is found along different crystal orientations with a quasi-cosinusoid
      function when the angle between the crystal orientation and polarization
      direction is changed from 0 degrees  to 180 degrees . Our experiments indicate
      that it is much easier (or more difficult) to form ripple structures when the
      polarization direction is aligned with the lattice axis [011]/[011-] (or [001]).
      The modulated nonlinear ionization rate along different crystal orientations,
      which arises from the direction dependence of the effective mass of the electron
      is proposed to interpret the unexpected anisotropic LIPSS formation phenomenon.
      Also, we demonstrate that the abnormal phenomenon can be applied to control the
      continuity of scanned ripple lines along different crystal orientations. 

PMID- 24875992
TI  - High-power beam transport through a hollow-core photonic bandgap fiber.
AB  - We investigate the use of a seven-cell hollow-core photonic bandgap fiber for
      transport of CW laser radiation from a single-mode, narrow-linewidth, high-power
      fiber laser amplifier. Over 90% of the amplifier output was coupled successfully
      and transmitted through the fiber in a near-Gaussian mode, with negligible
      backreflection into the source. 100 W of power was successfully transmitted
      continuously without damage and 160 W of power was transmitted briefly before the
      onset of thermal lensing in the coupling optics. 

PMID- 24875991
TI  - Resolution enhancement of confocal microscopy by subtraction method with vector
      beams.
AB  - We proposed a subtraction method using vector beams for resolution enhancement in
      confocal microscopy. The imaging simulation revealed that the negative side lobe
      due to the excess subtraction resulted in the degradation of the object image.
      The subtraction imaging using vector beams demonstrated high spatial resolution
      with avoiding the negative side lobe. Further resolution enhancement beyond 100
      nm was predicted by using a flat-top beam obtained by the combination of beams
      with radial and azimuthal polarizations and a higher-order transverse mode
      azimuthally polarized beam without significant negative side lobe. 

PMID- 24875993
TI  - Modeling the temporal evolution of an aero-optical aberration with the minimum
      description length principle.
AB  - A method of building a dynamical model for temporal evolution of an aero-optical
      aberration is presented. Based on the proper orthogonal decomposition (POD) of
      the optical aberration, the minimum description length (MDL) principle is used to
      select a dynamical model for the POD coefficients. The MDL principle can balance
      the model error against model size so as to prevent the model from overfitting.
      This strategy is validated with the numerical simulation of the aero-optical
      aberration caused by the supersonic mixing layer, and the model obtained can
      accurately predict the time evolution of the POD coefficients in short time. The
      potential application of our method in extending the bandwidth of the adaptive
      optics system is also discussed. 

PMID- 24875994
TI  - Mechanical impedance measurement and damage detection using noncontact laser
      ultrasound.
AB  - This Letter proposes a mechanical impedance (MI) measurement technique using
      noncontact laser ultrasound. The ultrasound is generated by shooting a pulse
      laser beam onto a target structure, and its response is measured using a laser
      vibrometer. Once ultrasound propagation converges to structural vibration, MI is
      formed over the entire structure. Because noncontact lasers are utilized, this
      technique is applicable in harsh environments, free of electromagnetic
      interference, and able to perform wide-range scanning. The formation of MI and
      its feasibility for damage detection are verified through thermo-mechanical
      finite element analysis and lab-scale experiments. 

PMID- 24875995
TI  - Temporal focusing-based multiphoton excitation microscopy via digital micromirror
      device.
AB  - This Letter presents an enhanced temporal focusing-based multiphoton excitation
      (MPE) microscope in which the conventional diffraction grating is replaced by a
      digital micromirror device (DMD). Experimental results from imaging a thin
      fluorescence film show that the 4.0 MUm axial resolution of the microscope is
      comparable with that of a setup incorporating a 600  lines/mm grating; hence, the
      optical sectioning ability of the proposed setup is demonstrated. Similar to a
      grating, the DMD diffracts illuminating light frequencies for temporal focusing;
      additionally, it generates arbitrary patterns. Since the DMD is placed on the
      image-conjugate plane of the objective lens' focal plane, the MPE pattern can be
      projected on the focal plane precisely. 

PMID- 24875996
TI  - Narrow-line magneto-optical trap for dysprosium atoms.
AB  - We present our technique to create a magneto-optical trap (MOT) for dysprosium
      atoms using the narrow-line cooling transition at 626 nm to achieve suitable
      conditions for direct loading into an optical dipole trap. The MOT is loaded from
      an atomic beam via a Zeeman slower using the strongest atomic transition at 421
      nm. With this combination of two cooling transitions we can trap up to 2.0.10(8)
      atoms at temperatures down to 6 MUK. This cooling approach is simpler than
      present work with ultracold dysprosium and provides similar starting conditions
      for a transfer to an optical dipole trap.

PMID- 24875997
TI  - Influence of pollutants in the magneto-dielectric response of silicon
      nanoparticles.
AB  - The influence of the degree of purity of a silicon nanoparticle on its
      resonances, either electric or magnetic, is assessed by using Mie theory as well
      as finite-element simulations. In particular, it is shown that the main effect of
      the increase of absorption due to the pollutants is observed in the magnetic
      resonances. Concerning Kerker's conditions for the directionality of the
      scattering [J. Opt. Soc. Am.73, 765 (1983)], it is found that both are strongly
      shifted when the material's purity is varied. Resistive losses confirm the
      quenching of magnetic resonances, showing that the region of influence in the
      magnetic dipole resonance is much larger than in the electric one, although it
      has been found that losses are not critical for silicon content over 99.50%. 

PMID- 24875998
TI  - Multi-mJ, kHz, 2.1 MUm optical parametric chirped-pulse amplifier and high-flux
      soft x-ray high-harmonic generation.
AB  - We report on a multi-mJ 2.1 MUm optical parametric chirped-pulse amplification
      (OPCPA) system operating at 1 kHz repetition rate, pumped by a picosecond
      cryogenic Yb:YAG laser, and the demonstration of soft x-ray high-harmonic
      generation (HHG) with a flux of ~2*10(8)  photon/s/1% bandwidth at 160 eV in Ar.
      The 1 kHz cryogenic Yb:YAG pump laser amplifies pulses up to 56 mJ and delivers
      compressed 42 mJ, 17 ps pulses to the 2.1 MUm OPCPA system. In the three-stage
      OPCPA chain, we have obtained up to 2.6 mJ of output energies at 2.1 MUm and
      pulses compressed to 40 fs with good beam quality. Finally, we show cut-off
      extension of HHG driven by this 2.1 MUm source in Ar and N2 gas cells to 190 eV
      with high photon flux. Our 3D propagation simulation confirms the generation of
      soft x-ray attosecond pulses from the experiment with Ar.

PMID- 24875999
TI  - Uniqueness of the differential Mueller matrix of uniform homogeneous media.
AB  - We show that the differential matrix of a uniform homogeneous medium containing
      birefringence may not be uniquely determined from its Mueller matrix, resulting
      in the potential existence of an infinite set of elementary polarization
      properties parameterized by an integer parameter. The uniqueness depends on the
      symmetry properties of a special differential matrix derived from the eigenvalue
      decomposition of the Mueller matrix. The conditions for the uniqueness of the
      differential matrix are identified, physically discussed, and illustrated in
      examples from the literature. 

PMID- 24876000
TI  - Characterization of distributed modal birefringence in a few-mode fiber based on
      Brillouin dynamic grating.
AB  - We propose and demonstrate generation of Brillouin dynamic grating (BDG) in a few
      mode fiber (FMF) with a Gaussian pulse pump and a counterpropagating continuous
      wave pump in LP01 mode. Brillouin optical time-domain analysis (BOTDA) is
      achieved by launching a third Gaussian pulse probe in LP11 mode. With coherent
      detection and time-domain analysis on the backreflected probe signal, the modal
      birefringence of the FMF is characterized via the distributed BDG with high
      spatial resolution and high accuracy.

PMID- 24876001
TI  - Enhancement of diffraction efficiency via higher-order operation of a multilayer
      blazed grating.
AB  - Imperfections in the multilayer stack deposited on a saw-tooth substrate are the
      main factor limiting the diffraction efficiency of extreme ultraviolet and soft x
      ray multilayer-coated blazed gratings (MBGs). Since the multilayer perturbations
      occur in the vicinity of antiblazed facets of the substrates, reduction of the
      groove density of MBGs is expected to enlarge the area of unperturbed multilayer
      and result in higher diffraction efficiency. At the same time the grating should
      be optimized for higher-order operation in order to keep high dispersion and
      spectral resolution. In this work we show the validity of this approach and
      demonstrate significant enhancement of diffraction efficiency of MBGs using
      higher-order diffraction. A new record for diffraction efficiency of 52% in the
      second diffraction order was achieved for an optimized MBG with groove density of
      2525  lines/mm at the wavelength of 13.4 nm. 

PMID- 24876002
TI  - Efficient continuous-wave four-wave mixing in bandgap-engineered AlGaAs
      waveguides.
AB  - We present a side-by-side comparison of the nonlinear behavior of four passive
      AlGaAs ridge waveguides where the bandgap energy of the core layers ranges from
      1.60 to 1.79 eV. By engineering the bandgap to suppress two-photon absorption,
      minimizing the linear loss, and minimizing the mode area, we achieve efficient
      wavelength conversion in the C-band via partially degenerate four-wave mixing
      with a continuous-wave pump. The observed conversion efficiency
      [Idler(OUT)/Signal(IN)=-6.8  dB] is among the highest reported in passive
      semiconductor or glass waveguides. 

PMID- 24876003
TI  - Dynamic generation of plasmonic bottle-beams with controlled shape.
AB  - We demonstrate the generation of plasmonic bottle-beams based on self
      accelerating surface plasmons. These beams are excited from free-space beams
      through a special binary phase mask. The mask generates two mirror-imaged self
      accelerating surface plasmons, which form the plasmonic bottle-beam and a hot
      spot at the point of convergence. The shape and area of the bottle-beams,
      together with the location of the hot-spot, are statically controlled by
      designing arbitrary convex trajectories for the two counter-accelerating beams
      and also are dynamically controlled by the illumination beam. 

PMID- 24876004
TI  - Extra-thin infrared camera for low-cost surveillance applications.
AB  - We designed a cheap broadband uncooled microimager operating in the long
      wavelength infrared range using only one lens at a minimal cost for the
      manufacturing process. The approach is based on thin optics where the device
      volume is small and therefore inexpensive materials can be used because some
      absorption can be tolerated. We have used a Fresnel lens on a thin silicon
      substrate. Up to now, Fresnel lenses have not been used for broadband imaging
      because of their chromatic properties. However, working in a relatively high
      diffraction order can significantly reduce chromatism. A prototype has been made
      for short range or indoor low-cost surveillance applications like people
      counting, and experimental images are presented. 

PMID- 24876005
TI  - Double metal subwavelength slit arrays interference to measure the orbital
      angular momentum and the polarization of light.
AB  - We put forward a double-slit interference device based on two metal subwavelength
      slit arrays to measure the orbital angular momentum (OAM) and the polarization of
      beams simultaneously. The subwavelength slit serves as a localized spatial
      polarizer, and each slit array can be regarded as a wide diffraction-slit. When
      an OAM beam is normally incident upon the two slit arrays, the interference
      fringes twist, and the displacement depends on the topological charge of OAM
      beams. We present a detailed theoretical analysis of this measurement model. This
      model does not need additional reference light and is a linear model. 

PMID- 24876006
TI  - Robust and accurate transient light transport decomposition via convolutional
      sparse coding.
AB  - Ultrafast sources and detectors have been used to record the time-resolved
      scattering of light propagating through macroscopic scenes. In the context of
      computational imaging, decomposition of this transient light transport (TLT) is
      useful for applications, such as characterizing materials, imaging through
      diffuser layers, and relighting scenes dynamically. Here, we demonstrate a method
      of convolutional sparse coding to decompose TLT into direct reflections, inter
      reflections, and subsurface scattering. The method relies on the sparsity
      composition of the time-resolved kernel. We show that it is robust and accurate
      to noise during the acquisition process. 

PMID- 24876007
TI  - Ultraviolet-to-visible downconversion luminescence in solgel oxyfluoride glass
      ceramics containing Eu3+:GdF3 nanocrystals.
AB  - GdF3 nanocrystals doped with Eu3+ ions in oxyfluoride glass ceramics were
      prepared by a solgel method. The structural properties were examined by x-ray
      diffraction measurements. The effects of gadolinium codoping on europium emission
      in the prepared solgel glasses and glass ceramics have been studied. The emission
      bands originating from the 5D0 state of Eu3+ ions are enhanced under excitation
      of Gd3+ ions by 273 nm line. The electric dipole 5D0->7F2 transitions were
      dominant in the samples before heat treatment, whereas magnetic dipole 5D0->7F1
      transitions had a higher probability in the samples after annealing. The
      luminescence lifetime for the 5D0 level of Eu3+ ions in the samples after
      excitation at 273 nm is long lived in comparison to excitation at 393 nm and
      increased to 190%. Energy transfer from Gd3+ to Eu3+ was observed.

PMID- 24876008
TI  - Enhancing intensity and refractive index sensing capability with infrared
      plasmonic perfect absorbers.
AB  - An infrared refractive index sensor based on plasmonic perfect absorbers for
      glucose concentration sensing is experimentally demonstrated. Utilizing
      substantial absorption contrast between a perfect absorber (~98% at normal
      incidence) and a non-perfect absorber upon the refractive index change, a maximum
      value of figure of merit (FOM<sup>*</sup>) about 55 and a bulk wavelength
      sensitivity about 590  nm/RIU are achieved. The demonstrated sensing platform
      provides great potential in improving the performance of plasmonic refractive
      index sensors and developing future surface enhanced infrared spectroscopy. 

PMID- 24876009
TI  - Dual-resonances approach to broadband cavity-assisted optical signal processing
      beyond the carrier relaxation rate.
AB  - We propose and analyze a differential control scheme for cavity-enhanced optical
      signal processing devices based on carrier nonlinearities. The scheme relies on
      two optical cavities to increase the bandwidth beyond the limit given by the
      slowest carrier relaxation rate of the medium. Practical implementations are
      envisioned using photonic crystal cavities, and the controls may be electrical or
      optical in nature. 

PMID- 24876010
TI  - High-power red, orange, and green Pr3+:LiYF4 lasers.
AB  - Laser experiments with Pr(3+):LiYF4 under excitation with a frequency doubled
      optically pumped semiconductor laser emitting 5 W at 479 nm were performed at
      seven different laser wavelengths of 523, 546, 604, 607, 640, 698, and 720 nm. At
      all these wavelengths the output power exceeded 1 W. The best performance at 523
      nm with an output power of 2.9 W at a slope efficiency of 72% and an optical-to
      optical efficiency of 67% with respect to the incident pump power represents the
      highest efficiency ever reported for a praseodymium-doped laser material.

PMID- 24876011
TI  - Wavefront aberration statistics in normal eye populations: are they well
      described by the Kolmogorov model?
AB  - This Letter studies the statistics of wavefront aberrations in a sample of eyes
      with normal vision. Methods relying on the statistics of the measured wavefront
      slopes are used, not including the aberration estimation stage. Power-law
      aberration models, an extension of the Kolmogorov one, are rejected by chi2-tests
      performed on fits to the slope structure function data. This is due to the large
      weight of defocus and astigmatism variations in normal eyes. Models of only
      second-order changes are not ruled out. The results are compared with previous
      works in the area.

PMID- 24876013
TI  - Plasmonic sectoral horn nanoantennas.
AB  - In this Letter, plasmonic sectoral horn nanoantennas working at near-infrared
      wavelength (1550 nm) have been investigated. We demonstrate that, although there
      are certain differences between the plasmonic and classical radiofrequency (RF)
      sectoral horn antennas, the plasmonic horns still possess a number of attractive
      features, like their RF counterparts, such as tunable high directivities,
      simplicity in fabrication, and ease of coupling to waveguides. As a specific
      application, we further show how to exploit these findings to optimize an optical
      wireless nanolink using the proposed horn nanoantennas, and obtain a 60-fold
      increase in the received power compared with the situation of matched dipole
      nanoantennas. 

PMID- 24876012
TI  - Optimization of fiber grating couplers on SOI using advanced search algorithms.
AB  - A one-dimensional fiber grating coupler is derived from a waveguide with random
      etches using implementations of particle swarm and genetic algorithms. The
      resulting gratings yield a theoretical coupling efficiency of up to 1.1 dB and
      prompt clear design rules for the layout of highly efficient fiber grating
      couplers.

PMID- 24876015
TI  - Low-threshold optical bistabilities in ultrathin nonlinear metamaterials.
AB  - Optical bistability typically occurs only when the optical thickness in the
      device or the input light power is unfavorably large. Here we show that, for a
      class of plasmonic metamaterials consisting of ultrathin holey metallic plates
      filled with nonlinear materials, the optical bistability can occur with an
      ultralow excitation power. We present a realistic design working at 0.2 THz and
      perform full-wave simulations to quantitatively study its optical bistability
      properties. An analytical model is developed to explain the inherent physics and
      provides a general design guideline for future development. 

PMID- 24876014
TI  - Laser-induced dispersion control.
AB  - An intense laser pulse is used to control the spectral phase of a weak probe
      pulse as they overlap in fused silica. The laser-induced linear chirp is
      controlled by the delay time between pulses. Dependence from intensity and
      spectral phase of the pump pulse is also studied. Experimental data is validated
      by numerical simulation based on optical Kerr effect. Results show that laser
      induced pulse shaping is possible and may be useful for intracavity pulse
      compression and shaping in enhancement cavities. 

PMID- 24876016
TI  - Hybrid booster at 1940 nm based on Tm:Lu2O3 ceramics implementing fiber combined
      signal and pump sources.
AB  - A novel concept of a booster amplifier for a pulsed Tm fiber laser at 1940 nm
      based on Tm:Lu2O3 ceramics and implementing fiber-combined signal and pump was
      examined. The pumping emission of the ceramics at 1678 nm was obtained from Raman
      shifted Er fiber laser radiation. The hybrid fiber-ceramics amplifier with a gain
      factor of up to 6 dB and a pulse energy of more than 650 MUJ with single-mode
      output was demonstrated.

PMID- 24876017
TI  - Enhanced photovoltaic performance of organic/silicon nanowire hybrid solar cells
      by solution-evacuated method.
AB  - A method has been developed to fabricate organic-inorganic hybrid heterojunction
      solar cells based on n-type silicon nanowire (SiNW) and poly (3,4
      ethylenedioxythiophene):poly (styrenesulfonate) (PEDOT:PSS) hybrid structures by
      evacuating the PEDOT:PSS solution with dip-dropping on the top of SiNWs before
      spin-coating (solution-evacuating). The coverage and contact interface between
      PEDOT:PSS and SiNW arrays can be dramatically enhanced by optimizing the solution
      evacuated time. The maximum power conversion efficiency (PCE) reaches 9.22% for a
      solution-evacuated time of 2 min compared with 5.17% for the untreated pristine
      device. The improvement photovoltaic performance is mainly attributed to better
      organic coverage and contact with an n-type SiNW surface. 

PMID- 24876018
TI  - Raman-induced gratings in atomic media.
AB  - A novel type of electromagnetically induced gratings based on the Raman
      nonlinearity in the field of standing pump waves are proposed. Unlike
      electromagnetically induced absorption gratings, these gratings are based on the
      spatial modulation of Raman susceptibility. We present a theoretical study of the
      optical response of such a spatial periodically modulated three-level atomic
      medium. It is shown that transmission and reflection of a probe Raman wave can be
      simultaneously amplified in the grating. Transmission and reflection spectra can
      be controlled by varying the pump field intensity. The basic mechanism
      responsible for all-optical control of transmission and reflection in the samples
      of Raman driven atoms are discussed. 

PMID- 24876019
TI  - Plasmonic bandpass filters with cascaded rectangular ring resonators.
AB  - We theoretically present the analysis and design of a nanoplasmonic bandpass
      filter with flat-top spectral characteristics by cascading a series of directly
      connected rectangular ring resonators based on metal-insulator-metal waveguides.
      Analyzed by the equivalent lumped circuit model of the transmission line to
      plasmonic waveguides, the transmission properties of a symmetric rectangular ring
      resonator with the directly connected input and output waveguides are
      approximately the same as that of a Fabry-Perot resonator. Then the thin-film
      design methodology is applied to realize a plasmonic bandpass filter with the
      squared passband. An example of cascaded two-rectangular ring resonator structure
      is numerically demonstrated by using the transmission line model and 2D finite
      difference time domain method. 

PMID- 24876020
TI  - High-brightness single-mode double-tapered laser diodes with laterally coupled
      high-order surface grating.
AB  - Double-tapered laser diodes with 23rd order laterally coupled surface gratings
      are fabricated at 913 nm. A narrow ridge waveguide restricts the lateral mode
      number, and tapered waveguides are utilized to enhance the output power. The
      gratings defined on the sides of ridge waveguide filter not only the longitudinal
      modes but also the high-order lateral modes. Experimentally, continuous wave
      power of over 560  mW/facet is achieved. The lateral far-field pattern exhibits a
      single-lobe profile and narrow divergence, and the lowest divergence angle is
      only twice the diffraction-limited one. The measured side-mode suppression ratio
      is about 27 dB. This device has great potential for high-power single-mode near
      diffraction-limited laser emission with easy fabrication. 

PMID- 24876021
TI  - Width and amplitude tunable square-wave pulse in dual-pump passively mode-locked
      fiber laser.
AB  - We have proposed and demonstrated a figure-8 dual-pump passively mode-locked
      fiber laser to generate square-wave pulse tunable by both width and amplitude.
      Just by simply adjusting the power of the pumps, both the amplitude and width of
      the output square-wave pulse can be tuned independently and continuously. One
      pump is used to tune the output pulsewidth while the other is used to tune
      amplitude. 

PMID- 24876022
TI  - Beat note stabilization of mode-locked lasers for quantum information processing.
AB  - We stabilize a chosen radio frequency beat note between two optical fields
      derived from the same mode-locked laser pulse train in order to coherently
      manipulate quantum information. This scheme does not require access or active
      stabilization of the laser repetition rate. We implement and characterize this
      external lock, in the context of two-photon stimulated Raman transitions between
      the hyperfine ground states of trapped 171Yb(+) quantum bits.

PMID- 24876023
TI  - Silicon single-crystal cryogenic optical resonator.
AB  - We report on the demonstration and characterization of a silicon optical
      resonator for laser frequency stabilization, operating in the deep cryogenic
      regime at temperatures as low as 1.5 K. Robust operation was achieved, with
      absolute frequency drift less than 20 Hz over 1 h. This stability allowed
      sensitive measurements of the resonator thermal expansion coefficient (alpha). We
      found that alpha=4.6*10(-13)  K(-1) at 1.6 K. At 16.8 K alpha vanishes, with a
      derivative equal to -6*10(-10)  K(-2). The temperature of the resonator was
      stabilized to a level below 10 MUK for averaging times longer than 20 s. The
      sensitivity of the resonator frequency to a variation of the laser power was also
      studied. The corresponding sensitivities and the expected Brownian noise indicate
      that this system should enable frequency stabilization of lasers at the low-10(
      17) level.

PMID- 24876024
TI  - Supercontinuum generation from 2 to 20 MUm in GaAs pumped by picosecond CO2 laser
      pulses.
AB  - We report on the generation of supercontinuum radiation from 2 to 20 MUm in a 67
      mm long GaAs crystal pumped by a train of 3 ps CO2 laser pulses. Temporal
      measurements indicate that sub-picosecond pulse splitting is involved in the
      production of such wide-bandwidth radiation in GaAs. The results show that the
      observed spectral broadening is heavily influenced by four-wave mixing and
      stimulated Raman scattering.

PMID- 24876025
TI  - Multifocal noncontact color imaging for depth-sensitive fluorescence measurements
      of epithelial cancer.
AB  - We propose a multifocal noncontact setup to perform depth-sensitive fluorescence
      imaging on a two-layered epithelial tissue model. The combination of a microlens
      array and a tunable lens enables the depth of the multifocal plane to be
      conveniently adjusted without any mechanical movement of the imaging lens or the
      sample. This advantage is particularly desirable in the clinical setting. Results
      from the phantom study demonstrate that the setup can achieve depth-sensitive
      color imaging for fluorescence measurements, which is further confirmed by
      spectral measurements. 

PMID- 24876026
TI  - Ultra-broadband wide-angle unidirectional plasmonic coupler based on joint
      effects of plasmonic critical angles and subwavelength metallic gratings.
AB  - A unidirectional plasmonic coupler with ultra-broadband and wide-angle coupling
      efficiency is proposed and demonstrated. Employing the plasmonic critical angle
      (PCA) phenomenon in conjunction with the effect of subwavelength metallic
      gratings, a wide incident angular full-width-half-maximum (AFWHM >28 degrees )
      coupling efficiency larger than 50% and extinction ratio better than 15 dB over
      an ultrabroad wavelength range 725-985 nm (bandwidth >260  nm) are achieved. The
      operation principle and performance of the structure are clarified and
      theoretically illustrated. 

PMID- 24876027
TI  - Diversity-multiplexing tradeoff in mode-division multiplexing.
AB  - The capacity of mode-division multiplexing (MDM) systems is limited, for a given
      outage probability, by mode-dependent loss (MDL) and gain. Modal degrees of
      freedom may be exploited to increase transmission rate (multiplexing gain) or
      lower outage probability (diversity gain), but there is a fundamental tradeoff
      between the achievable multiplexing and diversity gains. In this Letter, we
      present the diversity-multiplexing tradeoff in MDM systems for the first time,
      studying the impact of signal-to-noise ratio, MDL, and frequency diversity order
      on the tradeoff in the strong-mode-coupling regime. 

PMID- 24876028
TI  - Measurement of a compact colorless 3 dB hybrid plasmonic directional coupler.
AB  - We fabricated and measured a compact 3 dB hybrid plasmonic directional coupler
      for silicon photonics integrated circuits with a length of 21.2 MUm. The coupler
      has a 50?50 coupling ratio over a spectral bandwidth of more than 100 nm around a
      wavelength of 1.55 MUm and has an insertion loss of less than 1 dB. 

PMID- 24876029
TI  - Pulse dynamics in a mode-locked fiber laser and its quantum limited comb
      frequency uncertainty.
AB  - We present an experimental study of pulse dynamics in a mode-locked Er:fiber
      laser. By injecting a continuous wave laser with sinusoidal intensity modulation
      into the fiber laser, we are able to modulate the gain. Measuring the response of
      the pulse energy, central frequency, central pulse time, and phase to the gain
      modulation allows determination of the parameters that describe their coupling.
      Based on the experimentally derived parameters, we evaluate the free running comb
      linewidth and frequency uncertainty with feedback included, assuming quantum
      noise is the limiting factor. Optimization of fiber lasers is also discussed. 

PMID- 24876030
TI  - Two-crystal mid-infrared optical parametric oscillator for absorption and
      dispersion dual-comb spectroscopy.
AB  - We present a femtosecond optical parametric oscillator (OPO) containing two
      magnesium-doped periodically poled lithium niobate crystals in a singly resonant
      ring cavity, pumped by two mode-locked Yb-fiber lasers. As such, the OPO
      generates two idler combs (up to 220 mW), covering a wavelength range from 2.7 to
      4.2 MUm, from which a mid-infrared dual-comb Fourier transform spectrometer is
      constructed. By detecting the heterodyning signal between the two idler beams a
      full broadband spectrum of a molecular gas can be observed over 250  cm(-1)
      within 70 MUs with a spectral resolution of 15 GHz. The absorption and dispersion
      spectra of acetylene and methane have been measured around 3000  cm(-1),
      indicating that this OPO represents an ideal broadband mid-infrared source for
      fast chemical sensing.

PMID- 24876031
TI  - All-photoinduced terahertz optical activity.
AB  - We proposed and demonstrated active control of terahertz optical activity via
      chiral patterned photoexcitation in a semiconductor with a spatial light
      modulator (SLM). Arbitrary patterns can be generated by a SLM, including
      completely symmetric enantiomer pairs. This technique provides a new route to
      terahertz polarization modulators. 

PMID- 24876032
TI  - Coherent beam combination of Yb:YAG single-crystal rod amplifiers.
AB  - Coherent combination of ultrashort laser pulses emitted from spatially separated
      amplifiers is a promising power-scaling technique for ultrafast laser systems. It
      has been successfully applied to fiber amplifiers, since guidance of the signal
      provides the advantage of an excellent beam quality and straightforward
      superposition of beams as compared to bulk-type amplifier implementations. Herein
      we demonstrate, for the first time to our knowledge, a two-channel combining
      scheme employing Yb:YAG single-crystal rod amplifiers as an energy booster in a
      fiber chirped-pulse amplification system. In this proof-of-principle experiment,
      combined and compressed pulses with a duration of 695 fs and an energy of 3 mJ
      (3.7 GW of peak power) are obtained. The combining efficiency is as high as 94%
      and the beam quality of the combined output is characterized by a measured M2
      value of 1.2.

PMID- 24876033
TI  - Radially oscillating and quasi-guided surface plasmon polaritons in cylindrical
      metallic nanostructures.
AB  - We analytically propose radially oscillating and quasi-guided surface plasmon
      polaritons (SPPs) by designing the outer and core dielectric permittivities
      epsilon(a) and epsilon(c) of a cylindrical metallic nanotube. When the
      propagation constant satisfies ?epsilon(a)<Re(k(z)/k(0))<?epsilon(c), the
      electromagnetic field propagates along the radial direction in the core region
      and decays outside the nanotube, forming a standing radially oscillating SPP. In
      contrast, when ?epsilon(c)<Re(k(z)/k(0))<?epsilon(a), the electromagnetic field
      decays in the core region and propagates outside the nanotube, forming a quasi
      guided SPP. The propagation length of both SPPs can reach tens of micrometers, in
      particular, the radially oscillating SPPs have an ultrastrong light confinement.
      Finally, we design position-flexible broadband plasmonic router based on quasi
      guided SPPs, and we also discuss the advantages of a nanolaser based on radially
      oscillating SPPs.

PMID- 24876034
TI  - Imaging performance of finite uniaxial metamaterials with large anisotropy.
AB  - Metamaterials with extreme anisotropy overcome the diffraction limit by
      supporting the propagation of otherwise evanescent waves. Recent experiments in
      slabs of wire media have shown that images deteriorate away from the longitudinal
      Fabry-Perot resonances of the slab. Existing theoretical models explain this
      using nonlocality, surface waves, and additional boundary conditions. We show
      that image aberrations can be understood as originating from cavity resonances of
      uniaxial media with large local axial permittivity. We apply a simple cavity
      resonator model and a transfer matrix approach to replicate salient experimental
      features of wire media hyperlenses. These results offer avenues to reduce
      observed imaging artefacts, and are applicable to all uniaxial media with large
      magnitude of the axial permittivity, e.g., wire media and layered media. 

PMID- 24876035
TI  - Optically controlled microwave phase shifter based on nonlinear polarization
      rotation in a highly nonlinear fiber.
AB  - This Letter reports an optically controlled microwave phase shifter with an ultra
      wideband working bandwidth and a full 360 degrees  phase shifting range based on
      nonlinear polarization rotation (NPR) in a highly nonlinear fiber (HNLF). A
      continuous wave probe light is modulated by a polarization modulator (PolM) that
      is driven by a microwave signal to be phase shifted. The optical carrier and the
      first-order sidebands of the probe light experience different phase shifts due to
      the NPR induced by the control light in the HNLF. An optical bandpass filter is
      used to realize single-sideband modulation of the probe light by removing one of
      the first-order sidebands, as well as to reject the control light. After
      detecting by a photodetector, the phase of the recovered microwave signal is
      continuously tunable by adjusting the power of the control light. The proposed
      approach is theoretically analyzed and experimentally verified. A full 360
      degrees  tunable phase shift is realized over an ultra-wideband frequency range
      from 8 to 38 GHz when the power of the control light is tuned from 0 to 570 mW.

PMID- 24876037
TI  - Microring-based ratio-metric wavelength monitor on silicon.
AB  - An integrated dual-ring ratio-metric wavelength monitor (DR-RMWM) with ultra-high
      wavelength resolution and compact size is demonstrated. Two microrings are used
      as the edge filters and designed to achieve an "X-type" spectral response in a
      particular wavelength range. It is fabricated with the CMOS-compatible
      fabrication process on the silicon-on-insulator. The measured wavelength
      resolution is 5 pm in a 1.2 nm wide wavelength range. By tuning the resonant
      wavelength thermally, the functional wavelength range can be shifted. The DR-RMWM
      can find applications in wavelength monitoring systems, especially the on-chip
      systems. 

PMID- 24876036
TI  - Fiber Bragg grating stabilization of a passively mode-locked 2.8 MUm Er3+:
      fluoride glass fiber laser.
AB  - We report the first stable mode-locking from an Er3+: fluoride glass fiber laser
      linear cavity operating near 3 MUm to the best of our knowledge. The linear
      cavity includes a saturable absorber mirror and a fiber Bragg grating to provide
      a controlled and wavelength selective feedback. The pulse train has a 51.75 MHz
      repetition rate, an estimated 60 ps pulse duration, and an average power of 440
      mW. The stable and self-starting mode-locking regime is confirmed by RF spectral
      measurements and is maintained over several hours.

PMID- 24876038
TI  - Rayleigh-Brillouin scattering of carbon dioxide.
AB  - The spectral line shape of spontaneous Rayleigh-Brillouin scattering in CO2 is
      studied in a range of pressures. The spectrum is influenced by the bulk viscosity
      eta(b), which is a relaxation phenomenon involving the internal degrees of
      freedom of the molecule. The associated relaxation rates can be compared to the
      frequency shift of the scattered light, which demands precise measurements of the
      spectral line shape. We find eta(b)=(5.7+/-0.6)*10(-6)  kg m(-1) s(-1) for the
      range of pressures p=2-4 bar and for room temperature conditions.

PMID- 24876039
TI  - High-power picosecond 355 nm laser based on La2CaB10O19 crystal.
AB  - Third harmonic generation experiments were performed on a type-I phase-matching
      La2CaB10O19 crystal cut at theta=49.4 degrees  and phi=0.0 degrees  with
      dimensions of 4.0  mm*4.0  mm*17.6  mm. A 1064 nm laser with a maximum average
      power of 35.2 W was employed as the fundamental light source, which has a pulse
      width of 10 picoseconds and a pulse repetition rate of 80 MHz. A type-I
      noncritical phase-matching LBO crystal was used to generate 532 nm lasers. By
      investigating a series of focusing lens combinations, a picosecond 355 nm laser
      of 5.3 W was obtained, which is the highest power of picosecond 355 nm laser
      based on a La2CaB10O19 crystal so far. The total conversion efficiency from 1064
      to 355 nm was up to 15.1%.

PMID- 24876040
TI  - Scaling in light scattering by sharp conical metal tips.
AB  - Using the electrostatic approximation, we analyze electromagnetic fields
      scattered by sharp conical metal tips, which are illuminated with light polarized
      along the tip axis. We establish scaling relations for the scattered field
      amplitude and phase, and verify the validity with numerical simulations. Analytic
      expressions for the wavelength at which the scattered field near the tip changes
      its direction and for the field decay near the tip extremity are obtained,
      relating these characteristics to the cone angle and metal permittivity. The
      results obtained have important implications for various tip-enhanced phenomena,
      ranging from Raman and scattering near-field imaging to photoemission
      spectroscopy and nano-optical trapping. 

PMID- 24876041
TI  - Single-step implementation of a multiple-target-qubit controlled phase gate
      without need of classical pulses.
AB  - We propose a simple method for achieving a multiqubit phase gate of one qubit
      simultaneously controlling n target qubits, by using three-level quantum systems
      (i.e., qutrits) coupled to a cavity or resonator. The gate can be realized via
      one operational step, without need of classical pulses, and by a virtual photon
      process. Thus, the gate operation is greatly simplified and decoherence from the
      cavity decay is much reduced, when compared with previous proposals. In addition,
      the operation time is independent of the number of qubits and no adjustment of
      the qutrit level spacings or the cavity frequency is needed during the operation.

PMID- 24876042
TI  - Simultaneous detection of rotational and translational motion in optical tweezers
      by measurement of backscattered intensity.
AB  - We describe a simple yet powerful technique of simultaneously measuring both
      translational and rotational motion of mesoscopic particles in optical tweezers
      by measuring the backscattered intensity on a quadrant photodiode (QPD). While
      the measurement of translational motion by taking the difference of the
      backscattered intensity incident on adjacent quadrants of a QPD is well known, we
      demonstrate that rotational motion can be measured very precisely by taking the
      difference between the diagonal quadrants. The latter measurement eliminates the
      translational component entirely and leads to a detection sensitivity of around
      50 mdeg at S/N of 2 for angular motion of a driven microrod. The technique is
      also able to resolve the translational and rotational Brownian motion components
      of the microrod in an unperturbed trap and can be very useful in measuring
      translation-rotation coupling of micro-objects induced by hydrodynamic
      interactions. 

PMID- 24876043
TI  - Near-infrared sensitive photorefractive device using polymer dispersed liquid
      crystal and BSO:Ru hybrid structure.
AB  - A near-infrared sensitive hybrid device, based on a Ru-doped BSO photorefractive
      substrate and polymer dispersed liquid crystal (PDLC) layer, is reported. It is
      found that the photoexcited charge carriers generated in the BSO:Ru substrate
      create an optically induced space charge field, sufficient to penetrate into the
      PDLC layer and to re-orient the LC molecules inside the droplets. Beam-coupling
      measurements at the Bragg regime are performed showing prospective amplification
      values and high spatial resolution. The proposed structure does not require
      indium tin oxide (ITO) contacts and alignment layers. Such a device allows all
      the processes to be controlled by light, thus opening further potential for real
      time image processing at the near-infrared range. 

PMID- 24876044
TI  - Isotope 87Rb Faraday anomalous dispersion optical filter at 420 nm.
AB  - We demonstrate a Faraday anomalous dispersion optical filter (FADOF) operating on
      5S(1/2)-6P(3/2) transition at 420 nm with a 5 cm long cell of 96.5% enriched 87Rb
      and measure the transmission as a function of the magnetic field and temperature.
      The isotope 87Rb FADOF achieves a peak transmission of 98% with a bandwidth of
      2.5 GHz when the temperature of the isotope 87Rb cell is 280 degrees C and the
      magnetic field is 500 G. The corresponding equivalent noise bandwidth is 5.9 GHz.
      The isotope 87Rb FADOF is applied to submarine communications, is used as the
      laser frequency stabilization for some atomic lines, and is also used as the pump
      laser in four-level Rb active optical clock.

PMID- 24876045
TI  - Confocal photoacoustic microscopy using a single multifunctional lens.
AB  - Photoacoustic microscopy (PAM) has remained one of the fastest developing
      biomedical imaging modalities in the past decade. The confocal strategy of
      optical illumination and acoustic detection is a way to boost the sensitivity of
      PAM. To achieve confocal PAM, current PAM systems utilize separate acoustic and
      optical converging devices, making the systems bulky and complicated. In this
      Letter, we demonstrate the use of a single-liquid lens to successfully achieve
      acoustic and optical confocal configuration for optical-resolution PAM (ORPAM).
      Using the lens with a numerical aperture of 0.43, we show that the resolution of
      the ORPAM system is 4.8 MUm with a significantly improved sensitivity of acoustic
      detection. We also apply this compact ORPAM system to in vivo imaging of the
      vasculature of a rat ear. 

PMID- 24876046
TI  - Phase-contrast microscopy at high x-ray energy with a laboratory setup.
AB  - We report on the design and realization of an x-ray imaging system for
      quantitative phase-contrast microscopy at high x-ray energy with laboratory-scale
      instrumentation. Phase and amplitude were separated quantitatively at x-ray
      energies up to 80 keV with micrometric spatial resolution. The accuracy of the
      results was tested against numerical simulations, and the spatial resolution was
      experimentally quantified by measuring a Siemens star phase object. This simple
      setup should find broad application in those areas of x-ray imaging where high
      energy and spatial resolution are simultaneously required and in those difficult
      cases where the sample contains materials with similar x-ray absorption. 

PMID- 24876047
TI  - Experimental study of turbulence-induced beam wander and deformation of a
      partially coherent beam.
AB  - We carry out an experimental study of the effect of spatial coherence on the beam
      wander and the deformation of a Gaussian Schell-model (GSM) beam propagating
      through thermally induced turbulence. It is demonstrated that a GSM beam with
      lower coherence indeed experiences smaller beam wander and deformation than that
      with higher coherence. Our experimental results are explained by the beam wander
      theory of partially coherent beam reasonably, and will be useful in free-space
      optical communications. 

PMID- 24876048
TI  - Temperature insensitive single-mode-multimode-single-mode fiber optic structures
      with two multimode fibers in series.
AB  - We propose and demonstrate a temperature insensitive single-mode-multimode-single
      mode fiber optic structure consisting of two in-series multimode fibers of
      appropriate lengths and of opposite temperature sensitivities. A simple
      approximate expression to estimate the required length ratio of the multimode
      fiber sections has also been derived whose prediction is found in good agreement
      with the experiment. The study should be useful in realizing various fiber optic
      devices based on multimode interference with zero temperature cross sensitivity. 

PMID- 24876049
TI  - Magneto-optic spatial light modulator with submicron-size magnetic pixels for
      wide-viewing-angle holographic displays.
AB  - Spatial light modulators (SLMs) with submicron-size pixels are promising devices
      for use in wide-viewing-angle glasses-free holographic 3D displays. In accordance
      with estimations, an SLM with 1 MUm pitch pixels can display holographic images
      over viewing angles of 30 deg. In the present work, we have studied magneto-optic
      SLMs (MOSLMs) with submicron-size pixels for wide-viewing-angle holographic
      displays that are driven by thermomagnetic recording. Amorphous TbFe films were
      used as a magneto-optic material. The MOSLM with an 800 nm diameter pixels array
      displayed wide-viewing-angle holographic images. These results demonstrated that
      MOSLMs with submicron-size pixels have promise for glasses-free holographic 3D
      displays. 

PMID- 24876050
TI  - Phase singularity diffusion.
AB  - We follow the trajectories of phase singularities at nulls of intensity in the
      speckle pattern of waves transmitted through random media as the frequency of the
      incident radiation is scanned in microwave experiments and numerical simulations.
      Phase singularities are observed to diffuse with a linear increase of the square
      displacement <R2> with frequency shift. The product of the diffusion coefficient
      of phase singularities in the transmitted speckle pattern and the photon
      diffusion coefficient through the random medium is proportional to the square of
      the effective sample length. This provides the photon diffusion coefficient and a
      method for characterizing the motion of dynamic material systems.

PMID- 24876051
TI  - Simultaneous measurement of position and color of single fluorescent emitters
      using diffractive optics.
AB  - We propose a method for simultaneously measuring the position and emission color
      of single fluorescent emitters based on the use of a large pitch diffraction
      grating in the emission light path. The grating produces satellite spots adjacent
      to the main spot; the relative distance between the spots is a measure for the
      emission wavelength. We present proof-of-principle experiments on beads and
      mixtures of quantum dots using a spatial light modulator for making a
      programmable diffraction grating. A wavelength precision of around 10 nm can be
      achieved for 1000 signal photons and practical background levels, while
      maintaining a localization precision of around 10 nm. 

PMID- 24876052
TI  - Shifted knife-edge aperture digital in-line holography for fluid velocimetry.
AB  - We describe a digital holography technique that, with the simplicity of an in
      line configuration, produces holograms where the real and virtual images are
      completely separated, as in an off-axis configuration. An in-line setup, in which
      the object is imaged near the sensor, is modified by placing a shifted knife-edge
      aperture that blocks half the frequency spectrum at the focal plane of the
      imaging lens. This simple modification of the in-line holographic configuration
      allows discriminating the virtual and real images. As a fluid velocimetry
      technique, the use of this aperture removes the minimum defocusing distance
      requisite and reduces the out-of-plane velocity measurement errors of classical
      in-line holography. Results with different test objects are shown. 

PMID- 24876053
TI  - Stable fiber delivery of radio-frequency signal based on passive phase
      correction.
AB  - A novel passive phase correction method for stable fiber transfer of radio
      frequency (RF) signal is proposed and demonstrated. By employing only one local
      oscillator and two frequency mixers in the local station, an RF signal received
      by an optical remote antenna unit is transmitted to the local station with very
      small phase jitter. An experiment is performed. When a 6 GHz RF signal is
      delivered through a 20 km single-mode fiber, effective cancellation of the RF
      signal's phase jitter induced by environmental perturbations is achieved. The
      residual jitter is less than 1.33 ps (about 0.05 rad). The proposed scheme
      requires no active mechanism to compensate the fiber-length fluctuations, and is
      thus compact, cost-effective, and easy to implement. 

PMID- 24876054
TI  - Diabetes attenuates the inhibitory effects of endomorphin-2, but not endomorphin
      1 on gastrointestinal transit in mice.
AB  - Diabetes affects the entire gastrointestinal tract from the esophagus to the
      anus. In the present study, the charcoal meal test was undertaken to evaluate and
      compare the effects of intracerebroventricular (i.c.v.) administration of
      endomorphins (EMs) on gastrointestinal transit in non-diabetic and diabetic mice.
      Significantly delayed gastrointestinal transit was found in both 4 and 8 weeks
      alloxan-induced diabetes compared to non-diabetes. Moreover, i.c.v. EM-1 and EM-2
      dose-dependently delayed gastrointestinal transit in non-diabetes and diabetes.
      The EM-1-induced inhibitory effects of gastrointestinal transit in 4 weeks
      diabetes were qualitatively similar to those of non-diabetes. However, at higher
      doses, the EM-1-induced effects in 8 weeks diabetes were largely enhanced.
      Different to EM-1, the EM-2-induced inhibition of gastrointestinal transit in
      diabetic mice was significantly attenuated compared to non-diabetic mice.
      Moreover, these effects were further decreased in 8 weeks diabetes. The delayed
      gastrointestinal transit effects caused by EM-1 may be primarily mediated by MU2
      opioid receptor in both non-diabetes and 4 weeks diabetes. Interestingly, in 8
      weeks diabetes, these effects were mediated by MU2- and delta-receptors. However,
      the inhibitory effects of EM-2 were mediated by MU1-opioid receptor, which
      exerted a reduced function in diabetes. Also, poor blood glucose control might
      result in the attenuated effects of EM-2. Our present results demonstrated that
      diabetes attenuates the inhibitory effects of EM-2, but not EM-1 on
      gastrointestinal transit in mice. The different effects of EM-1 and EM-2 on
      gastrointestinal transit in diabetes may be due to changes of opioid receptor
      subtypes and their functional responses. 

PMID- 24876055
TI  - Antiarrhythmic activity of some xanthone derivatives with beta1-adrenoceptor
      affinities in rats.
AB  - A series of aminoalkanolic derivatives of xanthone with high affinity for beta1
      adrenoceptors was evaluated for antiarrhythmic activity in the model of ischemia
      reperfusion in isolated hearts, as well as in barium chloride- and adrenaline
      induced model of arrhythmia. In order to better understand biological activity of
      studied compounds, the influence on beta2-adrenoceptors in guinea-pig trachea and
      vasorelaxant properties in rat aorta were evaluated. Furthermore, due to assessed
      antioxidant activity, some biochemical studies were also performed. All tested
      compounds showed prominent antiarrhythmic activity in the model of ventricular
      arrhythmias associated with coronary artery occlusion and reperfusion. In this
      experiment the most active was compound MH-97. Whereas, compound MH-82 was the
      most active in barium- and adrenaline-induced arrhythmia after i.v. or p.o.
      administration, respectively. These two compounds have higher affinity to beta1
      adrenoceptors than compound MH-87, thus it suggests that blocking properties of
      beta1-adrenoceptors are involved in the observed antiarrhythmic effects. All
      studied compounds have revealed antagonistic potency for beta2-adrenoceptors in
      tracheal smooth muscle, however weaker than that of propranolol. None of tested
      compounds demonstrated antioxidant effect. They also had weak calcium entry
      blocking activity. The results of this study suggest that new compounds with
      antiarrhythmic activity might be found in the group of xanthone derivatives. 

PMID- 24876056
TI  - Myricetin enhances osteogenic differentiation through the activation of canonical
      Wnt/beta-catenin signaling in human bone marrow stromal cells.
AB  - Myricetina flavonoid compound, has been reported to possess antioxidative,
      antiproliferative and anti-inflammatory effects. However, no study has yet
      investigated the effect of myricetin on osteogenic differentiation of human bone
      marrow stem cells (hBMSCs). This study was designed to investigate the effects of
      myricetin on osteogenic differentiation of hBMSCs in vitro. Cell viability was
      analyzed by MTT and osteogenic differentiation was evaluated by alkaline
      phosphatase (ALP) activity assay, Alizarin red S dye, real time-polymerase chain
      reaction (RT-PCR) and Western blot analysis. We found that the ALP activity and
      the mineralization of hBMSCs were enhanced by treatment with myricetin. Myricetin
      increased the mRNA expressions of Osteocalcin (OCN), Collagen type I (COL-I), ALP
      and Runt-related transcription factor 2 (RUNX2). Additionally, we found that
      myricetin activated the Wnt/beta-catenin pathway and increased the expression of
      several downstream genes including T-cell factor-1(TCF-1) and lymphoid enhancer
      factor-1 (LEF-1). Depletion of beta-catenin almost completely blocked the
      positive role of myricetin on osteogenic differentiation. Taken together, our
      findings suggest that myricetin enhanced osteogenic differentiation of hBMSCs by
      activating the Wnt/beta-catenin signaling. The study may aid in the development
      of a therapeutic approach utilizing myricetin for the enhancement of bone health
      and prevention of osteoporosis. 

PMID- 24876057
TI  - Promoting neurogenesis via Wnt/beta-catenin signaling pathway accounts for the
      neurorestorative effects of morroniside against cerebral ischemia injury.
AB  - Ischemic stroke is a leading cause of mortality and permanent disability in
      adults worldwide. Neurogenesis triggered by ischemia in the adult mammalian brain
      may provide insights into stroke treatment. Morroniside is an active component of
      sarcocarp of C. officinalis that have shown neuroprotective effects. The aim of
      the present study is to test whether morroniside promotes neurogenesis via
      Wnt/beta-catenin signaling pathway for brain recovery in a rat model of focal
      cerebral ischemia. Morroniside was administered intragastrically once daily at
      the concentrations of 30, 90 and 270 mg/kg for 7 days post-ischemia. Neurological
      functions were detected by Ludmila Belayev score tests. Endogenous neural stem
      cells responses were investigated with immunofluorescence staining of Ki-67 and
      Nestin to identify the neurogenesis in the subventricular zone (SVZ). The
      expression of proteins involved in and related to Wnt/beta-catenin signaling
      pathway was detected by western blotting analysis. Morroniside significantly
      promoted neurogenesis for brain recovery 7 days post-ischemia. Increased
      expression of Wnt 3a, beta-catenin and T-cell transcription factor-4 (Tcf-4),
      along with activation of downstream transcription factors Pax6 and neurogenin2
      (Ngn2), indicated that the neurorestorative effects of morroniside may be
      associated with Wnt/beta-catenin signaling pathway. These data provide support
      for understanding the mechanisms of morroniside in neurorestorative effects and
      suggest a potential new strategy for ischemic stroke treatment.

PMID- 24876059
TI  - The role of spinal serotonin receptor and alpha adrenoceptor on the antiallodynic
      effects induced by intrathecal milnacipran in chronic constriction injury rats.
AB  - Milnacipran, a reuptake inhibitor of noradrenaline (NA) and serotonin (5-HT),
      elicits an antiallodynic effect in rats with neuropathic pain; however, the role
      of NA and 5-HT receptors in the induction of the antiallodynic effect of
      milnacipran remains unclear. Thus, we examined the effects of prazosin as an
      alpha1 adrenoceptor antagonist, yohimbine as an alpha2 adrenoceptor antagonist,
      metergoline as a 5-HT1, 5-HT2 and 5-HT7 receptor antagonist, cyanopindolol as a 5
      HT1A/1B receptor antagonist, ketanserin as a 5-HT2 receptor antagonist, and
      ondansetoron as a 5-HT3 receptor antagonist on the antiallodynic effect of
      milnacipran in neuropathic rats with chronic constriction injury (CCI). The CCI
      rats expressed mechanical and thermal allodynia, which was attenuated by
      intrathecal injection of milnacipran. Yohimbine, but not prazosin, reversed the
      milnacipran-induced antiallodynic effect. The antiallodynic effect of milnacipran
      was also reversed by metergoline, ketanserin and ondansetron, while cyanopindolol
      reversed the antiallodynic effect on mechanical, but not thermal stimulation.
      Furthermore, c-Fos expression in lamina I/II of the spinal dorsal horn was
      enhanced by thermal stimulation and the enhanced expression of c-Fos was
      suppressed by milnacipran. This effect of milnacipran was reversed by yohimbine,
      metergoline, katanserin and ondansetron, but not prazosin. These results indicate
      that the effect of milnacipran on mechanical and thermal allodynia and c-Fos
      expression is elicited through the alpha2 adrenoceptor, but not alpha1
      adrenoceptor, and 5-HT2 and 5-HT3 receptors; furthermore, the 5-HT1A/1B receptor
      is involved in mechanical allodynia, but not thermal allodynia. 

PMID- 24876058
TI  - Dexmedetomidine increases the activity of excitatory amino acid transporter type
      3 expressed in Xenopus oocytes: the involvement of protein kinase C and
      phosphatidylinositol 3-kinase.
AB  - Dexmedetomidine, an alpha2 adrenergic agonist, has neuroprotective and
      anticonvulsant properties in addition to its sedative and anxiolytic effects. We
      hypothesized that dexmedetomidine would increase the activity of excitatory amino
      acid transporter type 3 (EAAT3) and that this effect would involve protein kinase
      C (PKC) and phosphatidylinositol 3-kinase (PI3K), two protein kinases known to
      regulate EAAT3 activity. EAAT3 was expressed in Xenopus oocytes by injecting its
      mRNA. Two-electrode voltage clamping was used to record membrane currents before,
      during, and after application of 30 MUM l-glutamate in the presence of 0.1-30 nM
      dexmedetomidine. Dexmedetomidine-treated oocytes were also exposed to a PKC
      activator (phorbol-12-myristate-13-acetate [PMA]), PKC inhibitors (chelerythrine,
      staurosporine, and calphostin C), and PI3K inhibitors (wortmannin and LY294002)
      before current measurement. Dexmedetomidine application resulted in a
      concentration-dependent increase in the EAAT3 activity in response to l
      glutamate. The kinetic study showed that dexmedetomidine significantly increased
      the Vmax without changing Km. Treatment of oocytes with PMA significantly
      increased transporter currents compared with controls, but treatment with
      dexmedetomidine plus PMA did not further increase the response compared with PMA
      or dexmedetomidine alone. In addition, pre-treatment of oocytes with PKC
      inhibitors and PI3K inhibitors significantly abolished the dexmedetomidine
      enhanced EAAT3 activity. These results suggest that dexmedetomidine increases the
      activity of EAAT3 expressed in Xenopus oocytes. PKC and PI3K seem to mediate this
      effect. These findings may explain the neuroprotective and anticonvulsant effects
      of dexmedetomidine.

PMID- 24876060
TI  - Role of hydrogen sulfide in the formalin-induced orofacial pain in rats.
AB  - Hydrogen sulfide (H2S) is a gasotransmitter synthesized in peripheral tissues by
      the enzyme cystathionine gamma-lyase (CSE). This gas has been documented to be
      involved in a wide variety of processes including inflammation and nociception.
      The aim of the present study was to investigate the role of the peripheral H2S
      pathway in nociceptive response to the orofacial formalin experimental model of
      pain. Orofacial pain was induced by subcutaneous injection of formalin (1.5%, 50
      ul) into the upper lip of rats, and the time spent rubbing the face was measured
      at 3-min intervals for 45 min. Formalin induced a marked biphasic pain (first
      phase: 0-3 min; second phase: 15-33 min). Pretreatment with H2S donor (Na2S; 90
      umol/kg), CSE inhibitor (propargylglycine; 26.5 and 88.4 umol/kg), or a
      preferential blocker of T-type Ca(2+) channels (mibefradil; 0.28 and 2.81
      umol/kg) attenuated the second phase of face rubbing when injected locally as
      well as systemically. Pretreatment with a selective blocker of K(+)ATP channels
      (glybenclamide; 2.81 umol/kg) suppressed the Na2S-mediated attenuation of the
      formalin-induced pain second phase. Taken together these results suggest that
      endogenously produced H2S plays a pronociceptive role probably via T-type Ca(2+)
      channels, whereas exogenous H2S exerts antinociceptive effects mediated by
      K(+)ATP channels.

PMID- 24876063
TI  - Psychosocial and sociodemographic correlates of life satisfaction among patients
      diagnosed with cancer in Jordan.
AB  - Cancer is a worldwide disease, and the psychosocial concerns are nearly universal
      among patients with cancer. The purpose of this study is to investigate the
      psychosocial correlates of life satisfaction among patients diagnosed with cancer
      in Jordan. A cross-sectional survey using 92 patients diagnosed with cancer used
      to collect data in regard to life satisfaction, depressive symptoms,
      psychological distress, coping, and perceived social support. In general, about
      50% of patients reported high level of life satisfaction and 50% of the patients
      reported moderate levels of ability to effectively cope with life situations.
      Moreover, 78% of patients reported that they had depressive symptoms and 45.3% of
      them reported that they had moderate to severe depressive symptoms. Depressive
      symptoms had significant and negative correlation with life satisfaction (r = 
      0.50, p < 0.001), and stress had weak nonsignificant correlation with life
      satisfaction (r = 0.05, p > 0.05). On the other hand, social support from others
      has positive and significant correlation with life satisfaction (r = 0.32, p <
      0.01). Marital status, times of admission, perceived social support from others,
      and depressive symptoms were significant predictors of life satisfaction. Health
      professionals need to integrate their medical care with psychosocial intervention
      early at admission and during follow-up care, so early detection of psychological
      disturbances will help to implement effective treatment plans.

PMID- 24876064
TI  - N-truncation and pyroglutaminylation enhances the opsonizing capacity of Abeta
      peptides and facilitates phagocytosis by macrophages and microglia.
AB  - Abnormal accumulations of amyloid-beta (Abeta)-peptides are one of the
      pathological hallmarks of Alzheimer's disease (AD). The precursor of the Abeta
      peptides, the amyloid precursor protein (APP), is also found in peripheral blood
      cells, but its function in these cells remains elusive. We previously observed
      that mononuclear phagocytes release Abeta-peptides during activation and
      phagocytosis, suggesting a physiologic role in inflammatory processes. Here, we
      show that supplementing the media with soluble N-terminally truncated Abeta(2-40)
      and Abeta(2-42) as well as Abeta(1-42) induced the phagocytosis of polystyrene
      particles (PSPs) by primary human monocytes. If the PSPs were pre-incubated with
      Abeta-peptides, phagocytosis was induced by all tested Abeta-peptide species. N
      terminally truncated Abeta(x-42) induced the phagocytosis of PSPs significantly
      more effectively than did Abeta(x-40). Similarly, the phagocytosis of Escherichia
      coli by GM-CSF- and M-CSF-elicited macrophages as well as microglia was
      particularly facilitated by pre-incubation with N-terminally truncated Abeta(x
      42). The proinflammatory polarization of monocytes was indicated by the reduced
      MSRI expression and IL-10 secretion after phagocytosis of PSPs coated with
      Abeta(1-42), Abeta(2-42) and Abeta(3p-42). Polarization of the macrophages by GM
      CSF reduced the phagocytic activity, but it did not affect the capabilities of
      Abeta-peptides to opsonize prey. Taken together, Abeta-peptides support
      phagocytosis as soluble factors and act as opsonins. Differential effects among
      the Abeta-peptide variants point to distinct mechanisms of interaction among
      monocytes/macrophages, prey and Abeta-peptides. A proinflammatory polarization
      induced by the phagocytosis of Abeta-peptide coated particles may provide a model
      for the chronic inflammatory reaction and sustained plaque deposition in AD.

PMID- 24876065
TI  - Analysis of myocardial temperature changes in conventional isolated coronary
      artery bypass grafting.
AB  - BACKGROUNDS: To determine whether cold blood cardioplegia (CBCP) can get over
      coronary artery lesions, we analyzed the relationship between myocardial
      temperature changes and lesion severity of major coronary arteries. METHODS AND
      RESULTS: From April 1991 to October 2003, we measured myocardial temperature
      before and after antegrade and retrograde delivery of CBCP in 492 patients
      undergoing conventional coronary artery bypass grafting. Stenotic severity of
      three major coronary arteries was classified into four grades according to
      preoperative coronary arteriography; grade 0 for 50 % or less, 1 for 75 %, 2 for
      90 %, 3 for 99 % or 100 %. We analyzed relationships between myocardial
      temperature changes [DeltaT-A (antegrade) & DeltaT-R (retrograde)] and the
      coronary artery lesion's severity. Average DeltaT-A of the right coronary artery
      had no relationship with stenotic grades. Mean DeltaT-A of the left anterior
      descending (LAD) became less and less in proportion to its stenotic grade [9.7 
      degrees C for grade 0, 8.2  degrees C for grade 1, 7.1  degrees C for grade 2,
      and 6.0  degrees C for grade 3, respectively, (p = 0.0042)]. DeltaT-A of the
      circumflex artery showed similar but weaker tendency than those of LAD.
      Significant inverse correlations were found between DeltaT-A and DeltaT-R1 in
      each territory (p < 0.001). CONCLUSIONS: Antegrade delivery was less effective in
      situations with tight proximal lesion, especially in the LAD territory.
      Retrograde delivery supplemented antegrade delivery. Myocardial temperature
      monitoring enables us to deal with inadequate cardioplegic delivery, and is a
      good indicator of myocardial protection.

PMID- 24876066
TI  - A novel dilute and shoot HPLC assay method for quantification of irbesartan and
      hydrochlorothiazide in combination tablets and urine using second generation C18
      bonded monolithic silica column with double gradient elution.
AB  - Irbesartan (IRB) and hydrochlorothiazide (HCT) are angiotensin-II receptor
      antagonist and thiazide-class diuretic compounds, respectively, which are in use
      in the treatment of hypertension. A novel dilute-and-shoot HPLC assay method for
      simultaneous quantification of IRB and HCT in fixed-dose combination tablets and
      urine samples was described. The separation of IRB, HCT and agomelatine (internal
      standard) was carried out using a second generation C18-bonded monolithic silica
      column (Chromolith((r)) High Resolution RP-18e, 100*4.6mm, Merck KGaA), utilizing
      both mobile phase and flow rate gradient elution programs. The analytes were
      detected at 230 nm wavelength using photodiode array detector within 24 minutes
      with high resolution, observing about 50 percent more peak capacity when using
      second generation C18-bonded monolithic silica column. Urine samples were
      introduced into the system effortlessly, with only filtration and subsequent
      dilution. Validation studies were performed according to the official
      recommendations of USP and ICH, and the developed method was successfully applied
      to pharmaceutical tablets and urine samples. 

PMID- 24876067
TI  - Direct analysis of 18 flavonol glycosides, aglycones and terpene trilactones in
      Ginkgo biloba tablets by matrix solid phase dispersion coupled with ultra-high
      performance liquid chromatography tandem triple quadrupole mass spectrometry.
AB  - Analysis and quality control of Ginkgo biloba have been comprehensively studied.
      However, little attention has been devoted to the simultaneous extraction and
      analysis of flavonols and terpene trilactones, especially for direct
      quantification of flavonol glycosides. This work described a rapid strategy for
      one-step extraction and quantification of the components. A matrix solid phase
      dispersion (MSPD) method was designed for the extraction of ginkgo ingredients
      and compared with the heat-reflux and ultrasonic extraction methods. An ultra
      high performance liquid chromatography (UHPLC)-tandem-triple-quadrupole-mass
      spectrometry (QQQ-MS) method was developed for detection of the 18 components,
      including 10 original flavonol glycosides, 3 aglycones, and 5 lactones.
      Subsequently, the proposed strategy was used for the analysis of 12 G. biloba
      tablets. Results showed that MSPD produced comparable extraction efficiency but
      consumed less time and required lower solvent volumes compared with conventional
      methods. Without hydrolysis, the concentration detected was much closer to the
      original in the sample. The total flavonol glycoside contents in ginkgo tablets
      ranged from 3.59 to 125.21MUgmg(-1), and the terpene trilactone varied from 3.45
      to 57.8MUgmg(-1) among different manufacturers. In conclusion, the proposed MSPD
      and UHPLC-QQQ-MS is rapid and sensitive in providing comprehensive profile of
      chemical constituents especially the genuine flavonol glycosides for improved
      quality control of ginkgo products. 

PMID- 24876068
TI  - Correlation study of retention data and antimalarial activity of 1,2,4,5-mixed
      tetraoxanes with their molecular structure descriptors and LSER parameters.
AB  - The chromatographic behavior of mixed 1,2,4,5-tetraoxanes, cholic and deoxycholic
      acid derivatives with distinct biological activity, was examined by high
      performance thin-layer chromatography in order to correlate their structure and
      retention. Chromatographic systems were consisted of RP-18 or CN-silica as
      stationary phase, and binary mixtures of water with methanol, dioxane or acetone
      as mobile phase. Based on the respective retentions, the lipophilicity of the
      investigated compounds was determined. Multiple linear regression and partial
      least squares have been used to select variables that best describe the behavior
      of the investigated compounds in chromatographic systems and to quantify
      influences of most important parameters. The validation and cross-validation of
      the QSRR model suggest its applicability for prediction and understanding of
      retention of congeners. The models indicate the importance of nonpolar properties
      of the solutes and their ability for hydrophobic interactions, as well as the
      importance of proton donating abilities, hydrophilic and pi interactions pointing
      out on that way the possible separation mechanism in the studied chromatographic
      systems. Observed correlations between structure and biological activity of mixed
      1,2,4,5-tetraoxanes, indicate that the antimalarial activity against W2 and D6
      Plasmodium falciparum strains, is governed by hydrophobic feature (measured with
      lipophilicity parameter), hydrophilic feature (measured with HLB, %HS, HB and HBA
      descriptors), and electronic feature (HOMO). 

PMID- 24876069
TI  - Halide selective anion recognition by an amide-triazolium axle containing
      [2]rotaxane.
AB  - A new rotaxane containing the 3-amido-phenyl-triazolium group incorporated into
      the interlocked structure's axle component has been prepared by a chloride anion
      templated clipping strategy. Proton NMR titration experiments reveal that the
      interlocked host displays a high degree of halide anion recognition in
      competitive 1 : 1 CDCl3-CD3OD solvent mixture. Chloride and bromide anions are
      bound strongly and selectively, with negligible complexation of the larger, more
      basic oxoanions, acetate and dihydrogen phosphate being observed. Density
      functional theory calculations on the related axle motifs 3-amido-phenyl
      triazolium, pyridinium bis-triazole and pyridinium bis-amide were performed, and
      indicate that the new rotaxane axle motif displays much weaker oxoanion binding
      than the pyridinium based systems. 

PMID- 24876070
TI  - TiO2/CdSe core-shell nanofiber film for photoelectrochemical hydrogen generation.
AB  - We report on a novel core-shell TiO2/CdSe nanofiber photoanode for
      photoelectrochemical hydrogen generation. The core-shell nanofiber films, with a
      hierarchical network structure, are prepared on fluorine-doped tin oxide coated
      substrates via electrospinning pyrolysis and chemical bath deposition. The
      hierarchical network structure shows significantly improved photoelectrochemical
      properties due, we believe, to possessing more active sites for the oxidation
      reaction and a larger TiO2/CdSe interface area for photogenerated charges'
      separation. The synthesis details are discussed to provide a generic route for
      preparing other similar photoanodes with hierarchical network structures. 

PMID- 24876072
TI  - S-shaped decanuclear heterometallic [Ni8Ln2] complexes [Ln(III) = Gd, Tb, Dy and
      Ho]: theoretical modeling of the magnetic properties of the gadolinium analogue.
AB  - The reaction of 8-quinolinol-2-carboaldoxime (LH2) with Ni(II) and Ln(III) salts
      afforded the heterometallic decanuclear compounds [Ni8Dy2(MU3
      OH)2(L)8(LH)2(H2O)6](ClO4)2.16H2O (1), [Ni8Gd2(MU3
      OH)2(L)8(LH)2(H2O)4(MeOH)2](NO3)2.12H2O (2), [Ni8Ho2(MU3
      OH)2(L)8(LH)2(H2O)4(MeOH)2](ClO4)2.2MeOH.12H2O (3) and [Ni8Tb2 (MU3
      OH)2(L)8(LH)2(MeOH)4(OMe)2].2CH2Cl2.8H2O (4). While compounds 1-3 are dicationic,
      compound 4 is neutral. These compounds possess an S-shaped architecture and
      comprise a long chain of metal ions bound to each other. In all the complexes,
      the eight Ni(II) and two Ln(III) ions of the multimetallic ensemble are hold
      together by two MU3-OH, eight dianionic (L(2-)) and two monoanionic oxime ligands
      (LH(-)) whereas compound 4 has two MU3-OH, eight dianionic (L(2-)), two
      monoanionic oxime ligands (LH(-)) and two terminal methoxy (MeO(-)) ligands. The
      central portion of the S-shaped molecular wire is made up of an octanuclear
      Ni(II) ensemble which has at its two ends the Ln(III) caps. Magnetic studies on 1
      4 reveal that the magnetic interactions between neighboring metal ions are
      negligible at room temperature. On the other hand, at lower temperatures in all
      the compounds anti-ferromagnetic interactions seem to be dominated. Analysis of
      the magnetic data for the Gd(III) derivative indicates Ni(II)-Ni(II) anti
      ferromagnetic interactions and Gd(III)-Ni(II) ferromagnetic interactions at low
      temperatures. A theoretical density functional study on the magnetic behavior of
      the Gd(III) derivative suggests that while the weak ferromagnetic interaction
      between Gd(III) and Ni(II) is in line with the expectation of the magnetic
      interactions between orthogonal d and f orbitals, antiferromagnetic Ni(II)-Ni(II)
      interactions are related to the wide Ni-O-Ni angles (~102 degrees ) and quasi
      planar conformation of the Ni2O2 core. 

PMID- 24876073
TI  - Trends of online ratings of otolaryngologists: what do your patients really think
      of you?
AB  - IMPORTANCE: The otolaryngologist's online reputation is of increasing importance.
      Physician rating websites are becoming increasingly prevalent, and patients are
      using them to evaluate their current and future physicians. OBJECTIVE: To
      evaluate patterns in online ratings of otolaryngologists. DESIGN, SETTING, AND
      PARTICIPANTS: From May 1, 2013, through June 1, 2013, lists of academic program
      faculty members in the Northeastern United States were compiled, and academic
      allopathic otolaryngologists from the Eastern Section of the Triological Society
      were identified. Each faculty member's name was searched using the Google search
      engine to link to profiles on the Healthgrades.com and Vitals.com websites. MAIN
      OUTCOMES AND MEASURES: State, program, academic position, years in practice,
      subspecialty, ratings, and reviews were recorded. Ratings were compared using
      analysis of variance. RESULTS: A total of 281 faculty members from 25 programs
      were identified. A total of 266 otolaryngologists (94.7%) had a profile on
      Healthgrades, and 247 (87.9%) had a profile on Vitals. Of those with profiles,
      186 (69.9%) and 202 (81.8%) had patient reviews on Healthgrades and Vitals,
      respectively. The mean score was 4.4 of 5.0 on Healthgrades and 3.4 of 4.0 on
      Vitals. On Vitals, 179 profiles (63.7%) had comments associated with them.
      Overall, 49 comments (27.3%) were determined to be negative, and 138
      otolaryngologists (49.1%) had at least 1 negative comment. Academic position and
      subspecialty affected reviews on Healthgrades. State and years in practice did
      not influence reviews. CONCLUSIONS AND RELEVANCE: Most patients use online
      resources for information on health care professionals. Physician perceptions of
      these sites tend to be negative. Awareness of the content and rating patterns may
      help physicians better manage their online reputation.

PMID- 24876071
TI  - Australia's arid-adapted butcherbirds experienced range expansions during
      Pleistocene glacial maxima.
AB  - A model of range expansions during glacial maxima (GM) for cold-adapted species
      is generally accepted for the Northern Hemisphere. Given that GM in Australia
      largely resulted in the expansion of arid zones, rather than glaciation, it could
      be expected that arid-adapted species might have had expanded ranges at GM, as
      cold-adapted species did in the Northern Hemisphere. For Australian biota,
      however, it remains paradigmatic that arid-adapted species contracted to refugia
      at GM. Here we use multilocus data and ecological niche models (ENMs) to test
      alternative GM models for butcherbirds. ENMs, mtDNA and estimates of nuclear
      introgression and past population sizes support a model of GM expansion in the
      arid-tolerant Grey Butcherbird that resulted in secondary contact with its close
      relative--the savanna-inhabiting Silver-backed Butcherbird--whose contemporary
      distribution is widely separated. Together, these data reject the universal use
      of a GM contraction model for Australia's dry woodland and arid biota.

PMID- 24876075
TI  - Therapeutic implications of melatonin in cerebral edema.
AB  - Cerebral edema/brain edema refers to the accumulation of fluid in the brain and
      is one of the fatal conditions that require immediate medical attention. Cerebral
      edema develops as a consequence of cerebral trauma, cerebral infarction,
      hemorrhages, abscess, tumor, hypoxia, and other toxic or metabolic factors. Based
      on the causative factors cerebral edema is differentiated into cytotoxic cerebral
      edema, vasogenic cerebral edema, osmotic and interstitial cerebral edema.
      Treatment of cerebral edema depends on timely diagnosis and medical assistance.
      Pragmatic treatment strategies such as antihypertensive medications, nonsteroidal
      anti-inflammatory drugs, barbiturates, steroids, glutamate and N-methyl-D
      aspartate receptor antagonists and trometamol are used in clinical practice.
      Although the above mentioned treatment approaches are being used, owing to the
      complexity of the mechanisms involved in cerebral edema, a single therapeutic
      strategy which could ameliorate cerebral edema is yet to be identified. However,
      recent experimental studies have suggested that melatonin, a neurohormone
      produced by the pineal gland, could be an effective alternative for treating
      cerebral edema. In animal models of stroke, melatonin was not only shown to
      reduce cerebral edema but also preserved the blood brain barrier. Melatonin's
      beneficial effects were attributed to its properties, such as being a potent anti
      oxidant, and its ability to cross the blood brain barrier within minutes after
      its administration. This review summarizes the beneficial effects of melatonin
      when used for treating cerebral edema.

PMID- 24876077
TI  - Improving the public health sector in South Africa: eliciting public preferences
      using a discrete choice experiment.
AB  - BACKGROUND: The introduction of national health insurance (NHI), aimed at
      achieving universal coverage, is the most important issue currently on the South
      African health policy agenda. Improvement in public sector health-care provision
      is crucial for the successful implementation of NHI as, regardless of whether
      health-care services become more affordable and available, if the quality of the
      services provided is not acceptable, people will not use the services. Although
      there has been criticism of the quality of public sector health services, limited
      research is available to identify what communities regard as the greatest
      problems with the services. METHODS: A discrete choice experiment (DCE) was
      undertaken to elicit public preferences on key dimensions of quality of care when
      selecting public health facilities in South Africa. Qualitative methods were
      applied to establish attributes and levels for the DCE. To elicit preferences,
      interviews with community members were held in two South African provinces: 491
      in Western Cape and 499 in Eastern Cape. RESULTS: The availability of necessary
      medicine at health facilities has the greatest impact on the probability of
      attending public health facilities. Other clinical quality attributes (i.e.
      provision of expert advice and provision of a thorough examination) are more
      valued than non-clinical quality of care attributes (i.e. staff attitude,
      treatment by doctors or nurses, and waiting time). Treatment by a doctor was less
      valued than all other attributes. CONCLUSION: Communities are prepared to
      tolerate public sector health service characteristics such as a long waiting
      time, poor staff attitudes and lack of direct access to doctors if they receive
      the medicine they need, a thorough examination and a clear explanation of the
      diagnosis and prescribed treatment from health professionals. These findings
      prioritize issues that the South African government must address in order to meet
      their commitment to improve public sector health-care service provision.

PMID- 24876076
TI  - The cost of a knowledge silo: a systematic re-review of water, sanitation and
      hygiene interventions.
AB  - Divisions between communities, disciplinary and practice, impede understanding of
      how complex interventions in health and other sectors actually work and slow the
      development and spread of more effective ones. We test this hypothesis by re
      reviewing a Cochrane-standard systematic review (SR) of water, sanitation and
      hygiene (WASH) interventions' impact on child diarrhoea morbidity: can greater
      understanding of impacts and how they are achieved be gained when the same papers
      are reviewed jointly from health and development perspectives? Using realist
      review methods, researchers examined the 27 papers for evidence of other impact
      pathways operating than assumed in the papers and SR. Evidence relating to four
      questions was judged on a scale of likelihood. At the 'more than possible' or
      'likely' level, 22% of interventions were judged to involve substantially more
      actions than the SR's label indicated; 37% resulted in substantial additional
      impacts, beyond reduced diarrhoea morbidity; and unforeseen actions by
      individuals, households or communities substantially contributed to the impacts
      in 48% of studies. In 44%, it was judged that these additional impacts and
      actions would have substantially affected the intervention's effect on diarrhoea
      morbidity. The prevalence of these impacts and actions might well be found
      greater in studies not so narrowly selected. We identify six impact pathways
      suggested by these studies that were not considered by the SR: these are
      tentative, given the limitations of the literature we reviewed, but may help
      stimulate wider review and primary evaluation efforts. This re-review offers a
      fuller understanding of the impacts of these interventions and how they are
      produced, pointing to several ways in which investments might enhance health and
      wellbeing. It suggests that some conclusions of the SR and earlier reviews should
      be reconsidered. Moreover, it contributes important experience to the continuing
      debate on appropriate methods to evaluate and synthesize evidence on complex
      interventions. 

PMID- 24876079
TI  - Inhibition of serotonin reuptake by antidepressants and cerebral microbleeds in
      the general population.
AB  - BACKGROUND AND PURPOSE: Serotonin reuptake inhibiting antidepressants decrease
      platelet aggregation. This may cause an increased risk of intracerebral
      hemorrhage. However, the risk of subclinical microbleeds, which are highly
      prevalent in middle-aged and elderly people, is unknown. We studied whether
      serotonin reuptake inhibiting antidepressants increase the frequency of cerebral
      microbleeds and secondarily whether they lower the presence of ischemic vascular
      damage. METHODS: Within the population-based Rotterdam Study, information on
      antidepressant use was obtained from continuously monitored pharmacy records.
      Brain MRI was available in 4945 participants (55% women, mean age 64 years)
      between 2005 and 2011. We categorized antidepressants based on affinity for the
      serotonin transporter: high, intermediate, or low. Microbleeds (presence and
      location) and ischemic lesions (lacunes, white matter lesions) were rated on MRI.
      Logistic and linear regression, adjusted for age, sex, depressive symptoms, and
      cardiovascular risk were used to study the association of antidepressants with
      microbleeds and ischemic vascular lesions. RESULTS: Antidepressant use with
      strong serotonin reuptake inhibition was not associated with microbleed presence
      (odds ratio compared with nonuse, 1.03; confidence interval, 0.75-1.39)
      irrespective of microbleed location in the brain. Exclusion of antithrombotic
      users or persons with cortical infarcts did not change our results. Furthermore,
      serotonin reuptake inhibition was not related to ischemic vascular brain damage.
      CONCLUSIONS: In the general population, use of serotonin reuptake inhibiting
      antidepressants is not related to presence of cerebral microbleeds. This
      strengthens the idea that the platelet inhibitor effects of antidepressant drugs
      with affinity for serotonin are minimal and further supports the safety of
      selective serotonin reuptake inhibitors for nongastrointestinal bleedings.

PMID- 24876078
TI  - Association of kidney disease measures with ischemic versus hemorrhagic strokes:
      pooled analyses of 4 prospective community-based cohorts.
AB  - BACKGROUND AND PURPOSE: Although low glomerular filtration rate (GFR) and
      albuminuria are associated with increased risk of stroke, few studies compared
      their contribution to risk of ischemic versus hemorrhagic stroke separately. We
      contrasted the association of these kidney measures with ischemic versus
      hemorrhagic stroke. METHODS: We pooled individual participant data from 4
      community-based cohorts: 3 from the United States and 1 from The Netherlands. GFR
      was estimated using both creatinine and cystatin C, and albuminuria was
      quantified by urinary albumin-to-creatinine ratio (ACR). Associations of
      estimated GFR and ACR were compared for each stroke type (ischemic versus
      intraparenchymal hemorrhagic) using study-stratified Cox regression. RESULTS:
      Among 29,595 participants (mean age, 61 [SD 12.5] years; 46% men; 17% black),
      1261 developed stroke (12% hemorrhagic) during 280,549 person-years. Low
      estimated GFR was significantly associated with increased risk of ischemic
      stroke, but not hemorrhagic stroke, whereas high ACR was associated with both
      stroke types. Adjusted hazard ratios for ischemic and hemorrhagic stroke at
      estimated GFR of 45 (versus 95) mL/min per 1.73 m2 were 1.30 (95% confidence
      interval, 1.01-1.68) and 0.92 (0.47-1.81), respectively. In contrast, the
      corresponding hazard ratios for ACR of 300 (versus 5) mg/g were 1.62 (1.27-2.07)
      for ischemic and 2.57 (1.37-4.83) for hemorrhagic stroke, with significantly
      stronger association with hemorrhagic stroke (P=0.04). For hemorrhagic stroke,
      the association of elevated ACR was of similar magnitude as that of elevated
      systolic blood pressure. CONCLUSIONS: Whereas albuminuria showed significant
      association with both stroke types, the association of decreased estimated GFR
      was only significant for ischemic stroke. The strong association of albuminuria
      with both stroke types warrants clinical attention and further investigations.

PMID- 24876080
TI  - Hospital-directed feedback to Emergency Medical Services improves prehospital
      performance.
AB  - BACKGROUND AND PURPOSE: A potential way to improve prehospital stroke care and
      patient handoff is hospital-directed feedback for emergency medical service (EMS)
      providers. We evaluated whether a hospital-directed EMS stroke follow-up tool
      improved documentation of adherence to the Rhode Island state prehospital stroke
      protocol for EMS providers. METHODS: A standardized, 10-item feedback tool was
      developed in 2012 and sent to EMS directors for every transported patient with a
      discharge diagnosis of ischemic stroke. We reviewed patient charts meeting these
      criteria between January 2008 and December 2013. Performance on the tool was
      compared between the preintervention (January 2008 through January 2012) and
      postintervention (February 2012 through December 2013) periods. RESULTS: We
      identified 1176 patients with ischemic stroke who arrived by EMS in the study
      period: 668 in the preintervention period and 508 in the postintervention period.
      The overall score for the preintervention group was 5.31 and for the
      postintervention group 6.42 (P<0.001). Each of the 10 items, except checking
      blood glucose, showed statistically significant improvement in the
      postintervention period compared with the preintervention period. CONCLUSIONS:
      Hospital-directed feedback to EMS was associated with improved overall compliance
      with state protocols and documentation of 9 out of 10 individual items. Future
      confirmatory studies in different locales and studies on the impact of this
      intervention on actual tissue-type plasminogen activator administration rates and
      EMS personnel knowledge and behavior are needed.

PMID- 24876081
TI  - Impact of collaterals on successful revascularization in Solitaire FR with the
      intention for thrombectomy.
AB  - BACKGROUND AND PURPOSE: Collaterals at angiography before endovascular therapy
      were analyzed to ascertain the effect on a novel end point of successful
      revascularization without symptomatic hemorrhage in the Solitaire FR With the
      Intention for Thrombectomy (SWIFT) study. METHODS: Collateral grade (American
      Society of Interventional and Therapeutic Neuroradiology/Society of
      Interventional Radiology) on baseline angiography was independently assessed,
      blind to other data, with statistical analyses delineating the relationship with
      clinical, laboratory, and imaging parameters. RESULTS: Angiographic data on
      collaterals were available in 119 of 144 subjects (mean age, 67+/-12 years; 52%
      woman; median National Institutes of Health Stroke Scale, 18 [range, 8-28]).
      Worse collaterals were noted in subjects with elevated baseline blood glucose
      (P=0.013) and those with elevated baseline systolic blood pressure (P=0.039).
      Multivariate predictors of partial or worse collaterals included absence of prior
      hypertension (odds ratio, 4.049, P=0.012), smoking history (odds ratio, 3.822;
      P=0.013), and higher blood glucose (odds ratio, 1.017; P=0.022). Collaterals were
      strongly related to Alberta Stroke Program Early CT Score (ASPECTS) at baseline
      (0-1: median 8 [3-10]; 2-9 [5-10]; 3-9 [7-10]; 4-9 [8-10]; P<0.001) and 24 hours
      (0-1: median 1 [0-5]; 2-6 [0-10]; 3-8 [0-10]; 4-8 [4-8]; P<0.001). Better
      collaterals were linked with Thrombolysis in Cerebral Infarction 2b/3 reperfusion
      (P=0.019), better median National Institutes of Health Stroke Scale at day
      7/discharge (P<0.001), and better day 90 modified Rankin Scale (P<0.001). Better
      collateral grade was associated with successful revascularization without
      symptomatic hemorrhage, mean 2.3 (95% confidence interval, 2.1-2.5) versus 1.9
      (95% confidence interval, 1.7-2.2), P=0.021. CONCLUSIONS: Better collaterals were
      associated with lower glucose, lower blood pressure, smaller baseline infarcts in
      SWIFT, and greater likelihood of successful revascularization without hemorrhage
      and good clinical outcomes. CLINICAL TRIAL REGISTRATION URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT01054560.

PMID- 24876083
TI  - Stroke mortality rates vary in local communities in a metropolitan area: racial
      and spatial disparities and correlates.
AB  - BACKGROUND AND PURPOSE: For the past decade, stroke has held steady as one of the
      top 4 leading causes of death in the United States. Aggregated data provide
      information about how the country or individual states are faring with respect to
      stroke mortality, but disaggregation provides data that may facilitate targeted
      interventions and community engagement. METHODS: We analyzed deaths from stroke
      to residents of Chicago to calculate age-adjusted stroke mortality rates
      (AASMRs). We calculated AASMRs for Chicago by race/ethnicity, sex, and community
      area. We also examined the correlation between AASMR and (1) racial/ethnic
      composition of a community area and (2) median household income. RESULTS: The
      AASMR for Chicago (44.9 per 100,000 population) was significantly higher than the
      national rate (42.2). Within both the United States and Chicago, the highest
      AASMRs were found among non-Hispanic blacks, followed by non-Hispanic whites, and
      then Hispanics. There was a strong, positive correlation between the proportion
      of black residents in a community area and the AASMR (0.58). There was a strong,
      negative relationship between household income and the AASMR for the entire city
      (-0.56) and for the predominantly black community areas (-0.47). CONCLUSIONS:
      These data provide insight into where the worst stroke mortality problems reside
      in Chicago. We anticipate that the data can be used to work toward the
      development of solutions to the high stroke mortality rates observed in several
      of Chicago's community areas and in similar communities throughout the United
      States.

PMID- 24876082
TI  - Predictors of functional dependence despite successful revascularization in large
      vessel occlusion strokes.
AB  - BACKGROUND AND PURPOSE: High revascularization rates in large-vessel occlusion
      strokes treated by mechanical thrombectomy are not always associated with good
      clinical outcomes. We evaluated predictors of functional dependence despite
      successful revascularization among patients with acute ischemic stroke treated
      with thrombectomy. METHODS: We analyzed the pooled data from the Multi Mechanical
      Embolus Removal in Cerebral Ischemia (MERCI), Thrombectomy Revascularization of
      Large Vessel Occlusions in Acute Ischemic Stroke (TREVO), and TREVO 2 trials.
      Successful revascularization was defined as thrombolysis in cerebral infarction
      score 2b or 3. Functional dependence was defined as a score of 3 to 6 on the
      modified Rankin Scale at 3 months. We assessed relationship of demographic,
      clinical, angiographic characteristics, and hemorrhage with functional dependence
      despite successful revascularization. RESULTS: Two hundred and twenty-eight
      patients with successful revascularization had clinical outcome follow-up. The
      rates of functional dependence with endovascular success were 48.6% for Trevo
      thrombectomy and 58.0% for Merci thrombectomy. Age (odds ratio, 1.04; 95%
      confidence interval, 1.02-1.06 per 1-year increase), National Institutes of
      Health Stroke Scale score (odds ratio, 1.08; 95% confidence interval, 1.02-1.15
      per 1-point increase), and symptom onset to endovascular treatment time (odds
      ratio, 1.11; 95% confidence interval, 1.01-1.22 per 30-minute delay) were
      predictors of functional dependence despite successful revascularization. Symptom
      onset to reperfusion time beyond 5 hours was associated with functional
      dependence. All subjects with symptomatic intracranial hemorrhage had functional
      dependence. CONCLUSIONS: One half of patients with successful mechanical
      thrombectomy do not have good outcomes. Age, severe neurological deficits, and
      delayed endovascular treatment were associated with functional dependence despite
      successful revascularization. Our data support efforts to minimize delays to
      endovascular therapy in patients with acute ischemic stroke to improve outcomes.
      CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique
      identifier: NCT00318071, NCT01088672, and NCT01270867.

PMID- 24876085
TI  - Decision making in acute stroke care: learning from neuroeconomics,
      neuromarketing, and poker players.

PMID- 24876084
TI  - Endoglin deficiency impairs stroke recovery.
AB  - BACKGROUND AND PURPOSE: Endoglin deficiency causes hereditary hemorrhagic
      telangiectasia-1 and impairs myocardial repair. Pulmonary arteriovenous
      malformations in patients with hereditary hemorrhagic telangiectasia-1 are
      associated with a high incidence of paradoxical embolism in the cerebral
      circulation and ischemic brain injury. We hypothesized that endoglin deficiency
      impairs stroke recovery. METHODS: Eng heterozygous (Eng+/-) and wild-type mice
      underwent permanent distal middle cerebral artery occlusion (pMCAO). Pial
      collateral vessels were quantified before pMCAO. Infarct/atrophic volume,
      vascular density, and macrophages were quantified in various days after pMCAO,
      and behavioral function was assessed using corner and adhesive removal tests on
      days 3, 15, 30, and 60 after pMCAO. The association between ENG 207G>A
      polymorphism and brain arteriovenous malformation rupture and surgery outcome was
      analyzed using logistic regression analysis in 256 ruptured and 157 unruptured
      patients. RESULTS: After pMCAO, Eng+/- mice showed larger infarct/atrophic
      volumes at all time points (P<0.05) and showed worse behavior performance
      (P<0.05) at 15, 30, and 60 days when compared with wild-type mice. Eng+/- mice
      had fewer macrophages on day 3 (P=0.009) and more macrophages on day 60 (P=0.02)
      in the peri-infarct region. Although Eng+/- and wild-type mice had similar
      numbers of pial collateral vessels before pMCAO, Eng+/- mice had lower vascular
      density in the peri-infarct region (P=0.05) on day 60 after pMCAO. In humans, ENG
      207A allele has been associated with worse outcomes after arteriovenous
      malformation rupture or surgery of patients with unruptured arteriovenous
      malformation. CONCLUSIONS: Endoglin deficiency impairs brain injury recovery.
      Reduced angiogenesis, impaired macrophage homing, and delayed inflammation
      resolution could be the underlying mechanism.

PMID- 24876086
TI  - Primary preventive potential for stroke by avoidance of major lifestyle risk
      factors: the European Prospective Investigation into Cancer and Nutrition
      Heidelberg cohort.
AB  - BACKGROUND AND PURPOSE: Because primary prevention of stroke is a priority, our
      aim was to assess the primary preventive potential of major lifestyle risk
      factors for stroke in middle-aged women and men. METHODS: Among 23,927 persons,
      551 (195 women and 356 men) had a first diagnosis of stroke during an average
      follow-up of 12.7 years. Using Cox proportional hazards models, we estimated the
      associations of adiposity, smoking, physical activity, alcohol consumption, and
      diet with risk of developing stroke. A competing risk model built from cause
      specific proportional hazards models accounting for concurrent risk of death was
      used to calculate relative and absolute reductions in stroke occurrences that
      could have been achieved by maintaining a healthy lifestyle pattern. RESULTS:
      Obesity, smoking, alcohol consumption, diet, and physical inactivity were each
      identified as modifiable lifestyle risk factors for stroke. About 38% of stroke
      cases were estimated as preventable through adherence to a healthy lifestyle
      profile (never smoking, maintaining optimal body mass index and waist
      circumference, performing physical exercise, consuming a moderate quantity of
      alcohol, and following a healthy dietary pattern). Age-specific estimates of 5
      year incidence rates for stroke in the actual cohort and in a hypothetical,
      comparable cohort of individuals following a healthy lifestyle would be reduced
      from 153 to 94 per 100,000 women and from 261 to 161 per 100,000 men for the age
      group 60 to 65 years. CONCLUSIONS: Our analysis confirms the strong primary
      prevention potential for stroke based on avoidance of excess body weight,
      smoking, heavy alcohol consumption, unhealthy diet, and physical inactivity.

PMID- 24876087
TI  - Unexplained early neurological deterioration after intravenous thrombolysis:
      incidence, predictors, and associated factors.
AB  - BACKGROUND AND PURPOSE: Early neurological deterioration (END) after anterior
      circulation stroke is a serious clinical event strongly associated with poor
      outcome. Regarding specifically END occurring within 24 hours of intravenous
      recombinant tissue-type plasminogen activator, apart from definite causes such as
      symptomatic intracranial hemorrhage and malignant edema whose incidence,
      predictors, and clinical management are well established, little is known about
      END without clear mechanism (ENDunexplained). METHODS: We analyzed 309
      consecutive patients thrombolysed intravenously <=4.5 hours from onset of
      anterior circulation stroke. ENDunexplained was defined as a >=4-point
      deterioration on 24-hour National Institutes of Health Stroke Scale, without
      definite mechanism on concomitant imaging. ENDunexplained and no-END patients
      were compared for pretreatment clinical and imaging (including magnetic resonance
      diffusion and diffusion/perfusion mismatch volumes) data and 24-hour post
      treatment clinical (including blood pressure and glycemic changes) and imaging
      (24-hour recanalization) data, using univariate logistic regression. Exploratory
      multivariate analysis was also performed after variable reduction, with bootstrap
      analysis for internal validation. RESULTS: Among 33 END patients, 23 (7% of whole
      sample) had ENDunexplained. ENDunexplained was associated with poor 3-month
      outcome (P<0.01). In univariate analysis, admission predictors of ENDunexplained
      included no prior use of antiplatelets (P=0.02), lower National Institutes of
      Health Stroke Scale score (P<0.01), higher glycemia (P=0.03), larger mismatch
      volume (P=0.03), and proximal occlusion (P=0.01), with consistent results from
      the multivariate analysis. Among factors recorded during the first 24 hours, only
      no recanalization was associated with ENDunexplained in multivariate analysis
      (P=0.02). CONCLUSIONS: ENDunexplained affected 7% of patients and accounted for
      most cases of END. Several predictors and associated factors were identified,
      with important implications regarding underlying mechanisms and potential
      prevention of this ominous event.

PMID- 24876088
TI  - Selective serotonin reuptake inhibitors and risk of cerebral bleeding.

PMID- 24876089
TI  - The CAVE score for predicting late seizures after intracerebral hemorrhage.
AB  - BACKGROUND AND PURPOSE: Seizures are a common complication of intracerebral
      hemorrhage (ICH). We developed a novel tool to quantify this risk in individual
      patients. METHODS: Retrospective analysis of the observational Helsinki ICH Study
      (n=993; median follow-up, 2.7 years) and the Lille Prognosis of InTra-Cerebral
      Hemorrhage (n=325; 2.2 years) cohorts of consecutive ICH patients admitted
      between 2004 and 2010. Helsinki ICH Study patients' province-wide electronic
      records were evaluated for early seizures occurring within 7 days of ICH and
      among 7-day survivors (n=764) for late seizures (LSs) occurring >7 days from ICH.
      A Cox regression model estimating risk of LSs was used to derive a prognostic
      score, validated in the Prognosis of InTra-Cerebral Hemorrhage cohort. RESULTS:
      Of the Helsinki ICH Study patients, 109 (11.0%) had early seizures within 7 days
      of ICH. Among the 7-day survivors, 70 (9.2%) patients developed LSs. The
      cumulative risk of LSs was 7.1%, 10.0%, 10.2%, 11.0%, and 11.8% at 1 to 5 years
      after ICH, respectively. We created the CAVE score (0-4 points) to estimate the
      risk of LSs, with 1 point for each of cortical involvement, age<65 years,
      volume>10 mL, and early seizures within 7 days of ICH. The risk of LSs was 0.6%,
      3.6%, 9.8%, 34.8%, and 46.2% for CAVE scores 0 to 4, respectively. The c
      statistic was 0.81 (0.76-0.86) and 0.69 (0.59-0.78) in the validation cohort.
      CONCLUSIONS: One in 10 patients will develop seizures after ICH. The risk of this
      adverse outcome can be estimated by a simple score based on baseline variables.

PMID- 24876090
TI  - 16S ribosomal DNA sequence-based identification of bacteria in laboratory
      rodents: a practical approach in laboratory animal bacteriology diagnostics.
AB  - Correct identification of bacteria is crucial for the management of rodent
      colonies. Some bacteria are difficult to identify phenotypically outside
      reference laboratories. In this study, we evaluated the utility of 16S ribosomal
      DNA (rDNA) sequencing as a means of identifying a collection of 30 isolates of
      rodent origin which are conventionally difficult to identify. Sequence analysis
      of the first approximate 720 to 880 bp of the 5'- end of 16S rDNA identified 25
      isolates (83.33%) with >= 99% similarity to a sequence of a type strain, whereas
      three isolates (10%) displayed a sequence similarity >= 97% but <99% to the type
      strain sequences. These similarity scores were used to define identification to
      species and genus levels, respectively. Two of the 30 isolates (6.67%) displayed
      a sequence similarity of >= 95 but <97% to the reference strains and were thus
      allocated to a family. This technique allowed us to document the association of
      mice with bacteria relevant for the colonies management such as Pasteurellaceae,
      Bordetella hinzii or Streptococcus danieliae. In addition, human potential
      pathogens such as Acinetobacter spp., Ochrobactrum anthropi and Paracoccus yeei
      or others not yet reported in mouse bacterial species such as Leucobacter
      chironomi, Neisseria perflava and Pantoea dispersa were observed. In conclusion,
      the sequence analysis of 16S rDNA proved to be a useful diagnostic tool, with
      higher performance characteristics than the classical phenotypic methods, for
      identification of laboratory animal bacteria. For the first time this method
      allowed us to document the association of certain bacterial species with the
      laboratory mouse.

PMID- 24876091
TI  - A simplified necropsy technique for mice: making the most of unscheduled deaths.
AB  - Sudden or unexpected deaths in experimental mice can be potential causes of lost
      data or lost opportunities to diagnose health problems. In small animal units and
      in particular out of normal working hours there may not be the time or expertise
      available to attempt a careful dissection on unscheduled mortalities or moribund
      animals. This paper outlines a robust and easy necropsy technique which can be
      easily learnt, uses minimal equipment and can be used to implement the 3Rs
      (replacement, refinement and reduction) by maximizing the amount of information
      gained from experimental animals. 

PMID- 24876092
TI  - Excimer emission in norepinephrine and epinephrine drugs with alpha- and beta
      cyclodextrins: spectral and molecular modeling studies.
AB  - The inclusion complexation behavior of norepinephrine (NORE) and epinephrine
      (EPIN) with native cyclodextrins (alpha-CD and beta-CD) were investigated by UV
      visible, fluorimetry, time-resolved fluorescence, SEM, TEM, FT-IR, (1)H NMR, DSC,
      powder XRD and PM3 methods. Single emission was observed in aqueous solution
      where as dual emission (excimer) noticed in the CD solutions. Both drugs form 1:1
      drug-CD complexes in lower CD concentrations and 1:2 CD-drug2 complexes in the
      higher CD concentrations. Time-resolved fluorescence studies indicated that both
      drugs showed single exponential decay in water and biexponential decay in CD.
      Nano-sized self-aggregated particles of drug-CD were found by TEM studies.
      Molecular modeling studies indicated that aliphatic chain part of the drug was
      entrapped in the CD cavity. Thermodynamic parameters and binding affinity of
      complex formation of the CD were determined according to PM3 method. The PM3
      results were in good agreement with the experimental results. 

PMID- 24876096
TI  - Brain drain causing severe tricuspid regurgitation.

PMID- 24876095
TI  - Autophagy contributes to gefitinib-induced glioma cell growth inhibition.
AB  - Epidermal growth factor receptor tyrosine kinase inhibitors, including gefitinib,
      have been evaluated in patients with malignant gliomas. However, the molecular
      mechanisms involved in gefitinib-mediated anticancer effects against glioma are
      incompletely understood. In the present study, the cytostatic potential of
      gefitinib was demonstrated by the inhibition of glioma cell growth, long-term
      clonogenic survival, and xenograft tumor growth. The cytostatic consequences were
      accompanied by autophagy, as evidenced by monodansylcadaverine staining of acidic
      vesicle formation, conversion of microtubule-associated protein-1 light chain 3
      II (LC3-II), degradation of p62, punctate pattern of GFP-LC3, and conversion of
      GFP-LC3 to cleaved-GFP. Autophagy inhibitor 3-methyladenosine and chloroquine and
      genetic silencing of LC3 or Beclin 1 attenuated gefitinib-induced growth
      inhibition. Gefitinib-induced autophagy was not accompanied by the disruption of
      the Akt/mammalian target of rapamycin signaling. Instead, the activation of liver
      kinase-B1/AMP-activated protein kinase (AMPK) signaling correlated well with the
      induction of autophagy and growth inhibition caused by gefitinib. Silencing of
      AMPK suppressed gefitinib-induced autophagy and growth inhibition. The crucial
      role of AMPK activation in inducing glioma autophagy and growth inhibition was
      further supported by the actions of AMP mimetic AICAR. Gefitinib was shown to be
      capable of reducing the proliferation of glioma cells, presumably by autophagic
      mechanisms involving AMPK activation.

PMID- 24876093
TI  - Concurrent dendritic cell vaccine and strontium-89 radiation therapy in the
      management of multiple bone metastases.
AB  - BACKGROUND: In addition to its direct cytotoxic effects, radiation therapy
      renders tumor cells more susceptible to T cell-mediated cytotoxicity by
      modulating cell surface molecules involved in antigen presentation. The purpose
      of the present study was to determine the benefit of combined 89Sr radiation and
      dendritic cell (DC) vaccine therapy in bone metastasis patients. METHODS:
      Patients were treated with intravenous 89Sr at a dose of 40 MUCi/kg of body
      weight on the first day after the peripheral blood mononuclear cell collection.
      Seven days later, patients received DCs once a week for 6 weeks. The first three
      vaccines were administered by intravenous infusion, and the last three vaccines
      were administered by 24-point intradermal injection. Clinical response was
      evaluated by the number of bone metastatic foci demonstrated on bone
      scintigraphy; cell-mediated cytotoxicity response was evaluated by delayed-type
      hypersensitivity (DTH) reaction. All treatment-related toxicities including
      vaccine-induced fever and 89Sr-associated hematological toxicity were carefully
      monitored. RESULTS: Twenty-six patients with histologically diagnosed with
      primary cancers and multiple bone metastases demonstrated on bone scintigraphy
      were studied. The overall survival rate was 58.3%. The total positive DTH rate
      was 50%. The efficiency rate for pain relief was 60% (6/10), for quantity of life
      was 80%, and for clinic responses was 90%. Out of 10 cases, the Grade 1 or 2 of
      hematological depression in 4, erythema in 1, and fever in 7 were observed.
      CONCLUSIONS: The study has important implications for that combined 89Sr
      radiation, and DC vaccine therapy can benefit cancer patients with bone
      metastasis.

PMID- 24876094
TI  - Blood lipid profile and BMI-Z-score in adolescents with hyperuricemia.
AB  - BACKGROUND: Numerous studies have demonstrated that elevated serum uric acid
      concentration (SUA) is correlated with lipid profile in hypertensive or obese
      patients. However, the relationship between serum uric acid levels and lipid
      profile in non-obese late adolescent population was not examined before. AIMS: In
      this study we decided to assess the potential relationship between SUA and lipid
      profile, according to gender in adolescents with HU. METHODS: The study group
      comprises 607 Polish adolescents (474 males, 133 females) with HU. Retrospective
      analysis included demographic, clinical, and laboratory data. Lipid profile was
      assessed including total cholesterol (TC), low-density lipoprotein cholesterol
      (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), total
      cholesterol to HDL-C ratio (TC/HDL-C). RESULTS: In the examined group 187/607
      (31%) of teenagers were diagnosed with metabolic syndrome (MetS). Median BMI-Z
      score was 1.11 Q1-Q3: (-0.02-2.03) and both females and males in the upper
      tertile of SUA had statistically significant higher BMI-Z-score. The males in the
      upper tertile of serum uric acid levels also had higher values of TG and lower of
      HDL-C. In females, we have not found significant differences in lipid profile.
      Multiple regression analyses indicated that male gender, BMI-Z-score, and
      presence of hypertension correlated significantly with serum uric acid
      concentration. CONCLUSIONS: In summary, the results of our study confirm higher
      prevalence of hyperuricemia in males when compared to females and a stronger
      association of HU with BMI-Z-score and lipid profile in male adolescents.
      Nevertheless, multiple regression does not confirm the independent association of
      SUA with lipid profile.

PMID- 24876097
TI  - Non-invasive vulnerable plaque imaging: how do we know that treatment works?
AB  - Atherosclerosis is an inflammatory disorder that can evolve into an acute
      clinical event by plaque development, rupture, and thrombosis. Plaque
      vulnerability represents the susceptibility of a plaque to rupture and to result
      in an acute cardiovascular event. Nevertheless, plaque vulnerability is not an
      established medical diagnosis, but rather an evolving concept that has gained
      attention to improve risk prediction. The availability of high-resolution imaging
      modalities has significantly facilitated the possibility of performing in vivo
      regression studies and documenting serial changes in plaque stability. This
      review summarizes the currently available non-invasive methods to identify
      vulnerable plaques and to evaluate the effects of the current cardiovascular
      treatments on plaque evolution. 

PMID- 24876098
TI  - Prognostic significance of p16 and its relationship with human papillomavirus in
      pharyngeal squamous cell carcinomas.
AB  - IMPORTANCE: The prognostic significance of p16 in squamous cell carcinoma (SCC)
      of the hypopharynx (HP) and nasopharynx (NP) and relationship between human
      papillomavirus (HPV) and p16 is unclear. OBJECTIVES: To evaluate the prognostic
      significance of p16 in pharyngeal subsites (oropharynx [OP], HP, and NP) and
      assess the relationship between HPV and p16 in the HP and NP. DESIGN, SETTING,
      AND PARTICIPANTS: Retrospective medical record review of 172 patients with SCC of
      the pharynx treated with definitive radiation therapy from 2002 to 2013 at a
      university tertiary referral center, with tissue available for
      immunohistochemical analysis. The median follow-up was 30.1 months.
      INTERVENTIONS: A total of 118 patients were treated with chemoradiation, and 54
      patients were treated with radiation alone. Immunohistochemical analysis for p16
      was performed for all tumors. Hypopharynx and NP tumors were tested for HPV using
      in situ hybridization, and NP tumors were tested for Epstein-Barr virus. MAIN
      OUTCOMES AND MEASURES: Overall survival, locoregional control, and disease-free
      survival were analyzed according to p16, HPV, and Epstein-Barr virus status.
      RESULTS: Thirty-two patients had HP SCC, 127 had OP SCC, and 13 had NP SCC. p16
      Was positive in the HP (34%), OP (66%), and NP (46%). Prevalence of HPV was 14%
      in the HP and 50% in the NP. As a test for HPV, p16 had a positive predictive
      value of 38% (HP) and 67% (NP) and a negative predictive value of 100% in HP and
      NP tumors. p16 Status was a significant predictor of all clinical outcomes for
      patients with OP SCC (P<.001), but not for patients with HP or NP SCC. Patients
      with Epstein-Barr virus- or HPV-associated NP SCC had improved clinical outcomes.
      CONCLUSIONS AND RELEVANCE: p16 Was not associated with improved outcomes in
      patients with HP or NP SCC. The positive predictive value of p16 as a test for
      HPV is too low for p16 testing alone in the HP and NP. However, p16 negativity is
      sufficient to rule out HPV. As a research approach, we recommend p16
      immunohistochemistry as a screening test for HPV in NP SCC and HP SCC followed by
      confirmatory HPV in situ hybridization when p16 positive.

PMID- 24876099
TI  - The correlation between carotid artery atherosclerosis and clinical ischemic
      heart disease in lupus patients.
AB  - AIM: The extent of subclinical atherosclerosis can be assessed by ultrasound
      measurement of carotid intima-media thickness (cIMT) and total plaque area (TPA).
      We aimed to investigate the correlation between measures of atherosclerosis as
      documented on imaging studies of the carotid vasculature and clinical coronary
      artery disease (CAD) in systemic lupus erythematosus (SLE). METHODS: The study
      patients were recruited from the University of Toronto prospective cohort of SLE
      patients. Patients who had a history of CAD were compared to those without CAD.
      TPA and cIMT were measured using high-resolution optimized ultrasound systems.
      Logistic regression models were used to investigate the strength of association
      between ultrasound measures of atherosclerosis and CAD. The strength of
      association as expressed by odds ratio (OR) was compared between TPA and cIMT.
      RESULTS: A total of 103 SLE patients were analyzed (27 patients with a history of
      CAD). Carotid IMT correlated only moderately with TPA (r = 0.43, p < 0.001). Both
      measures were significantly associated with the presence of CAD. However, TPA
      showed a stronger association than cIMT (OR 9.55 vs. 2.02, respectively). TPA was
      also more strongly associated with dyslipidemia and hypertension compared to
      cIMT. CONCLUSIONS: In SLE patients, cIMT correlates only moderately with TPA,
      suggesting that they measure different phenotypes of atherosclerosis. Carotid TPA
      correlated better than cIMT with cardiovascular risk factors and CAD, suggesting
      that it may serve as a better tool for the investigation of atherosclerosis in
      SLE.

PMID- 24876101
TI  - CBP-93872 inhibits NBS1-mediated ATR activation, abrogating maintenance of the
      DNA double-strand break-specific G2 checkpoint.
AB  - CBP-93872 was previously identified as a G2 checkpoint inhibitor using a cell
      based high-throughput screening system. However, its molecular actions as well as
      cellular targets are largely unknown. Here, we uncovered the molecular mechanisms
      underlying abrogation of the G2 checkpoint by CBP-93872. CBP-93872 specifically
      abrogates the DNA double-stranded break (DSB)-induced G2 checkpoint through
      inhibiting maintenance but not initiation of G2 arrest because of specific
      inhibition of DSB-dependent ATR activation. Hence, ATR-dependent phosphorylation
      of Nbs1 and replication protein A 2 upon DSB was strongly suppressed in the
      presence of CBP-93872. CBP-93872 did not seem to inhibit DNA-end resection, but
      did inhibit Nbs1-dependent and ssDNA-induced ATR activation in vitro in a dose
      dependent manner. Taken together, our results suggest that CBP-93872 is an
      inhibitor of maintenance of the DSB-specific G2 checkpoint and thus might be a
      strong candidate as the basis for a drug that specifically sensitizes p53-mutated
      cancer cells to DSB-inducing DNA damage therapy.

PMID- 24876100
TI  - Deliberate learning in health care: the effect of importing best practices and
      creative problem solving on hospital performance improvement.
AB  - This article examines the effect on quality improvement of two common but
      distinct approaches to organizational learning: importing best practices (an
      externally oriented approach rooted in learning by imitating others' best
      practices) and internal creative problem solving (an internally oriented approach
      rooted in learning by experimenting with self-generated solutions). We propose
      that independent and interaction effects of these approaches depend on where
      organizations are in their improvement journey - initial push or later phase. We
      examine this contingency in hospitals focused on improving treatment time for
      patients with heart attacks. Our results show that importing best practices helps
      hospitals achieve initial phase but not later phase improvement. Once hospitals
      enter the later phase of their efforts, however, significant improvement requires
      creative problem solving as well. Together, our results suggest that importing
      best practices delivers greater short-term improvement, but continued improvement
      depends on creative problem solving. 

PMID- 24876102
TI  - Neuromedin U: a candidate biomarker and therapeutic target to predict and
      overcome resistance to HER-tyrosine kinase inhibitors.
AB  - Intrinsic and acquired resistance to HER-targeting drugs occurs in a significant
      proportion of HER2-overexpressing breast cancers. Thus, there remains a need to
      identify predictive biomarkers that could improve patient selection and
      circumvent these types of drug resistance. Here, we report the identification of
      neuromedin U (NmU) as an extracellular biomarker in cells resistant to HER
      targeted drugs. NmU overexpression occurred in cells with acquired or innate
      resistance to lapatinib, trastuzumab, neratinib, and afatinib, all of which
      displayed a similar trend upon short-term exposure, suggesting NmU induction may
      be an early response. An analysis of 3,489 cases of breast cancer showed NmU to
      be associated with poor patient outcome, particularly those with HER2
      overexpressing tumors independent of established prognostic indicators. Ectopic
      overexpression of NmU in drug-sensitive cells conferred resistance to all HER
      targeting drugs, whereas RNAi-mediated attenuation sensitized cells exhibiting
      acquired or innate drug resistance. Mechanistic investigations suggested that NmU
      acted through HSP27 as partner protein to stabilize HER2 protein levels. We also
      obtained evidence of functional NmU receptors on HER2-overexpressing cells, with
      the addition of exogenous NmU eliciting an elevation in HER2 and EGFR expression
      along with drug resistance. Finally, we found that NmU seemed to function in cell
      motility, invasion, and anoikis resistance. In vivo studies revealed that NmU
      attenuation impaired tumor growth and metastasis. Taken together, our results
      defined NmU as a candidate drug response biomarker for HER2-overexpressing
      cancers and as a candidate therapeutic target to limit metastatic progression and
      improve the efficacy of HER-targeted drugs.

PMID- 24876103
TI  - Hyperpolarized [1-13C] glutamate: a metabolic imaging biomarker of IDH1
      mutational status in glioma.
AB  - Mutations of the isocitrate dehydrogenase 1 (IDH1) gene are among the most
      prevalent in low-grade glioma and secondary glioblastoma, represent an early
      pathogenic event, and are associated with epigenetically driven modulations of
      metabolism. Of particular interest is the recently uncovered relationship between
      the IDH1 mutation and decreased activity of the branched-chain amino acid
      transaminase 1 (BCAT1) enzyme. Noninvasive imaging methods that can assess BCAT1
      activity could therefore improve detection of mutant IDH1 tumors and aid in
      developing and monitoring new targeted therapies. BCAT1 catalyzes the
      transamination of branched-chain amino acids while converting alpha-ketoglutarate
      (alpha-KG) to glutamate. Our goal was to use (13)C magnetic resonance
      spectroscopy to probe the conversion of hyperpolarized [1-(13)C] alpha-KG to
      hyperpolarized [1-(13)C] glutamate as a readout of BCAT1 activity. We
      investigated two isogenic glioblastoma lines that differed only in their IDH1
      status and performed experiments in live cells and in vivo in rat orthotopic
      tumors. Following injection of hyperpolarized [1-(13)C] alpha-KG, hyperpolarized
      [1-(13)C] glutamate production was detected both in cells and in vivo, and the
      level of hyperpolarized [1-(13)C] glutamate was significantly lower in mutant
      IDH1 cells and tumors compared with their IDH1-wild-type counterparts.
      Importantly however, in our cells the observed drop in hyperpolarized [1-(13)C]
      glutamate was likely mediated not only by a drop in BCAT1 activity, but also by
      reductions in aspartate transaminase and glutamate dehydrogenase activities,
      suggesting additional metabolic reprogramming at least in our model.
      Hyperpolarized [1-(13)C] glutamate could thus inform on multiple mutant IDH1
      associated metabolic events that mediate reduced glutamate production.

PMID- 24876104
TI  - A recombinant reporter system for monitoring reactivation of an endogenously DNA
      hypermethylated gene.
AB  - Reversing abnormal gene silencing in cancer cells due to DNA hypermethylation of
      promoter CpG islands may offer new cancer prevention or therapeutic approaches.
      Moreover, such approaches may be broadly applicable to enhance the efficacy of
      radiotherapy, chemotherapy, or immunotherapy. Here, we demonstrate the powerful
      utility of a novel gene reporter system to permit studies of the dynamics,
      mechanisms, and translational relevance of candidate therapies of this type in
      human colon cancer cells. The reporter system is based on in situ modification of
      the endogenous locus of the tumor-suppressor gene SFRP1, a pivotal regulator of
      the Wnt pathway that is silenced by DNA hypermethylation in many colon cancers.
      The modified SFRP1-GFP reporter allele used remained basally silent, like the
      unaltered allele, and it was activated only by drug treatments that derepress
      gene silencing by reversing DNA hypermethylation. We used the established DNA
      methyltransferase inhibitor (DNMTi) 5-aza-deoxycitidine (DAC) to show how this
      system can be used to address key questions in the clinical development of
      epigenetic cancer therapies. First, we defined conditions for which clinically
      relevant dosing could induce sustained induction of RNA and protein. Second, we
      found that, in vivo, a more prolonged drug exposure than anticipated was
      essential to derepress gene silencing in significant cell numbers, and this has
      implications for generating effective anticancer responses in patients with
      hematopoietic or solid tumors. Finally, we discovered how histone deacetylase
      inhibitors (HDACi) alone, when administered to cells actively replicating DNA,
      can robustly reexpress the silenced gene with no change in promoter methylation
      status. Taken together, our findings offer a new tool and insights for devising
      optimal clinical experiments to evaluate DNMTi and HDACi, alone or in
      combination, and with other cancer treatments, as agents for the epigenetic
      management and prevention of cancer.

PMID- 24876105
TI  - miR-155 drives telomere fragility in human breast cancer by targeting TRF1.
AB  - Telomeres consist of DNA tandem repeats that recruit the multiprotein complex
      shelterin to build a chromatin structure that protects chromosome ends. Although
      cancer formation is linked to alterations in telomere homeostasis, there is
      little understanding of how shelterin function is limited in cancer cells. Using
      a small-scale screening approach, we identified miR-155 as a key regulator in
      breast cancer cell expression of the shelterin component TERF1 (TRF1). miR-155
      targeted a conserved sequence motif in the 3'UTR of TRF1, resulting in its
      translational repression. miR-155 was upregulated commonly in breast cancer
      specimens, as associated with reduced TRF1 protein expression, metastasis-free
      survival, and relapse-free survival in estrogen receptor-positive cases.
      Modulating miR-155 expression in cells altered TRF1 levels and TRF1 abundance at
      telomeres. Compromising TRF1 expression by elevating miR-155 increased telomere
      fragility and altered the structure of metaphase chromosomes. In contrast,
      reducing miR-155 levels improved telomere function and genomic stability. These
      results implied that miR-155 upregulation antagonizes telomere integrity in
      breast cancer cells, increasing genomic instability linked to poor clinical
      outcome in estrogen receptor-positive disease. Our work argued that miRNA
      dependent regulation of shelterin function has a clinically significant impact on
      telomere function, suggesting the existence of "telo-miRNAs" that have an impact
      on cancer and aging.

PMID- 24876107
TI  - Constraint-based soft tissue simulation for virtual surgical training.
AB  - Most of surgical simulators employ a linear elastic model to simulate soft tissue
      material properties due to its computational efficiency and the simplicity.
      However, soft tissues often have elaborate nonlinear material characteristics.
      Most prominently, soft tissues are soft and compliant to small strains, but after
      initial deformations they are very resistant to further deformations even under
      large forces. Such material characteristic is referred as the nonlinear material
      incompliant which is computationally expensive and numerically difficult to
      simulate. This paper presents a constraint-based finite-element algorithm to
      simulate the nonlinear incompliant tissue materials efficiently for interactive
      simulation applications such as virtual surgery. Firstly, the proposed algorithm
      models the material stiffness behavior of soft tissues with a set of 3-D strain
      limit constraints on deformation strain tensors. By enforcing a large number of
      geometric constraints to achieve the material stiffness, the algorithm reduces
      the task of solving stiff equations of motion with a general numerical solver to
      iteratively resolving a set of constraints with a nonlinear Gauss-Seidel
      iterative process. Secondly, as a Gauss-Seidel method processes constraints
      individually, in order to speed up the global convergence of the large
      constrained system, a multiresolution hierarchy structure is also used to
      accelerate the computation significantly, making interactive simulations possible
      at a high level of details. Finally, this paper also presents a simple-to-build
      data acquisition system to validate simulation results with ex vivo tissue
      measurements. An interactive virtual reality-based simulation system is also
      demonstrated. 

PMID- 24876106
TI  - Molecular imaging with bioluminescence and PET reveals viral oncolysis kinetics
      and tumor viability.
AB  - Viral oncolysis, the destruction of cancer cells by replicating virus, is an
      experimental cancer therapy that continues to be explored. The treatment paradigm
      for this therapy involves successive waves of lytic replication in cancer cells.
      At present, monitoring viral titer at sites of replication requires biopsy.
      However, repeat serial biopsies are not practically feasible for temporal
      monitoring of viral replication and tumor response in patients. Molecular imaging
      provides a noninvasive method to identify intracellular viral gene expression in
      real time. We imaged viral oncolysis and tumor response to oncolysis sequentially
      with bioluminescence and positron emission tomography (PET), revealing the
      kinetics of both processes in tumor xenografts. We demonstrate that virus
      replication cycles can be identified as successive waves of reporter expression
      that occur ~2 days after the initial viral tumor infection peak. These waves
      correspond to virions that are released following a replication cycle. The viral
      and cellular kinetics were imaged with Fluc and Rluc bioluminescence reporters
      plus two 18F-labeled PET reporters FHBG [9-(4-18F-fluoro-3-[hydroxymethyl] butyl)
      guanine] and FLT (18F-3'-deoxy-3-'fluorothymidine), respectively. Correlative
      immunohistochemistry on tumor xenograft sections confirmed in vivo results. Our
      findings show how PET can be used to identify virus replication cycles and for
      real-time measurements of intratumoral replicating virus levels. This noninvasive
      imaging approach has potential utility for monitoring viral oncolysis therapy in
      patients.

PMID- 24876108
TI  - Clinically relevant CNT dispersions with exceptionally high dielectric properties
      for microwave theranostic applications.
AB  - We present a formulation for achieving stable high-concentration (up to 20 mg/ml)
      aqueous dispersions of carbon nanotubes (CNTs) with exceptionally high microwave
      frequency (0.5-6 GHz) dielectric properties. The formulation involves
      functionalizing CVD-synthesized CNTs via sonication in nitric and sulfuric acid.
      The overall chemical integrity of the CNTs is largely preserved, as demonstrated
      via physical and chemical characterizations, despite significant shortening and
      functionalization with oxygen-containing groups. This is attributed to the
      protected inner walls of double-walled CNTs in the samples. The resulting CNT
      dispersions show greatly enhanced dielectric properties compared to a CNT-free
      control. For example, at 3 GHz, the average relative permittivity and effective
      conductivity across several 20 mg/ml CNT samples were increased by ~ 70% and ~
      400%, respectively, compared to the control. These CNT dispersions exhibit the
      stability and extraordinary microwave properties desired in systemically
      administered theranostic agents for microwave diagnostic imaging and/or thermal
      therapy.

PMID- 24876109
TI  - Comparative validation of single-shot optical techniques for laparoscopic 3-D
      surface reconstruction.
AB  - Intra-operative imaging techniques for obtaining the shape and morphology of soft
      tissue surfaces in vivo are a key enabling technology for advanced surgical
      systems. Different optical techniques for 3-D surface reconstruction in
      laparoscopy have been proposed, however, so far no quantitative and comparative
      validation has been performed. Furthermore, robustness of the methods to
      clinically important factors like smoke or bleeding has not yet been assessed. To
      address these issues, we have formed a joint international initiative with the
      aim of validating different state-of-the-art passive and active reconstruction
      methods in a comparative manner. In this comprehensive in vitro study, we
      investigated reconstruction accuracy using different organs with various shape
      and texture and also tested reconstruction robustness with respect to a number of
      factors like the pose of the endoscope as well as the amount of blood or smoke
      present in the scene. The study suggests complementary advantages of the
      different techniques with respect to accuracy, robustness, point density,
      hardware complexity and computation time. While reconstruction accuracy under
      ideal conditions was generally high, robustness is a remaining issue to be
      addressed. Future work should include sensor fusion and in vivo validation
      studies in a specific clinical context. To trigger further research in surface
      reconstruction, stereoscopic data of the study will be made publically available
      at www.open-CAS.com upon publication of the paper. 

PMID- 24876110
TI  - Including anatomical and functional information in MC simulation of PET and SPECT
      brain studies. Brain-VISET: a voxel-based iterative method.
AB  - Monte Carlo (MC) simulation provides a flexible and robust framework to
      efficiently evaluate and optimize image processing methods in emission
      tomography. In this work we present Brain-VISET (Voxel-based Iterative Simulation
      for Emission Tomography), a method that aims to simulate realistic [ (99m) Tc]
      SPECT and [ (18) F]-PET brain databases by including anatomical and functional
      information. To this end, activity and attenuation maps generated using high
      resolution anatomical images from patients were used as input maps in a MC
      projector to simulate SPECT or PET sinograms. The reconstructed images were
      compared with the corresponding real SPECT or PET studies in an iterative process
      where the activity inputs maps were being modified at each iteration. Datasets of
      30 refractory epileptic patients were used to assess the new method. Each set
      consisted of structural images (MRI and CT) and functional studies (SPECT and
      PET), thereby allowing the inclusion of anatomical and functional variability in
      the simulation input models. SPECT and PET sinograms were obtained using the
      SimSET package and were reconstructed with the same protocols as those employed
      for the clinical studies. The convergence of Brain-VISET was evaluated by
      studying the behavior throughout iterations of the correlation coefficient, the
      quotient image histogram and a ROI analysis comparing simulated with real
      studies. The realism of generated maps was also evaluated. Our findings show that
      Brain-VISET is able to generate realistic SPECT and PET studies and that four
      iterations is a suitable number of iterations to guarantee a good agreement
      between simulated and real studies. 

PMID- 24876111
TI  - Optoacoustic imaging of subcutaneous microvasculature with a class one laser.
AB  - We developed a combined imaging platform allowing optoacoustic and ultrasound
      imaging based on a low energy laser and a handheld probe. The device is based on
      a sensitive single element 35-MHz focused transducer, a 2-D piezoscanner and a
      dual-wavelength switchable Nd:YAG laser. Acoustical detection and optical
      illumination are confocal for optimization of optoacoustic signal-to-noise ratio.
      The system allows to scan over a range up to 12 mm *12 mm in xy-direction with an
      isotropic lateral resolution of about 90 MUm. Although the device is a class 1
      laser product having pulse energies in the range, in vivo images of subcutaneous
      microvasculature could be obtained from human skin with signal-to-noise levels as
      good as 20 dB. 

PMID- 24876112
TI  - It takes a spark to light a fire: kindling interest in nephrology careers.

PMID- 24876113
TI  - Risk of AKI with gentamicin as surgical prophylaxis.
AB  - In 2009, the Scottish government issued a target to reduce Clostridium difficile
      infection by 30% in 2 years. Consequently, Scottish hospitals changed from
      cephalosporins to gentamicin for surgical antibiotic prophylaxis. This study
      examined rates of postoperative AKI before and after this policy change. The
      study population comprised 12,482 adults undergoing surgery (orthopedic, urology,
      vascular, gastrointestinal, and gynecology) with antibiotic prophylaxis between
      October 1, 2006, and September 30, 2010 in the Tayside region of Scotland.
      Postoperative AKI was defined by the Kidney Disease Improving Global Outcomes
      criteria. The study design was an interrupted time series with segmented
      regression analysis. In orthopedic patients, change in policy from cefuroxime to
      flucloxacillin (two doses of 1 g) and single-dose gentamicin (4 mg/kg) was
      associated with a 94% increase in AKI (P=0.04; 95% confidence interval, 93.8% to
      94.3%). Most patients who developed AKI after prophylactic gentamicin had stage 1
      AKI, but some patients developed persistent stage 2 or stage 3 AKI. The
      antibiotic policy change was not associated with a significant increase in AKI in
      the other groups. Regardless of antibiotic regimen, however, rates of AKI were
      high (24%) after vascular surgery, and increased steadily after gastrointestinal
      surgery. Rates could only be ascertained in 52% of urology patients and 47% of
      gynecology patients because of a lack of creatinine testing. These results
      suggest that gentamicin should be avoided in orthopedic patients in the
      perioperative period. Our findings also raise concerns about the increasing
      prevalence of postoperative AKI and failures to consistently measure
      postoperative renal function. 

PMID- 24876114
TI  - Endogenous fructose production and fructokinase activation mediate renal injury
      in diabetic nephropathy.
AB  - Diabetes is associated with activation of the polyol pathway, in which glucose is
      converted to sorbitol by aldose reductase. Previous studies focused on the role
      of sorbitol in mediating diabetic complications. However, in the proximal tubule,
      sorbitol can be converted to fructose, which is then metabolized largely by
      fructokinase, also known as ketohexokinase, leading to ATP depletion,
      proinflammatory cytokine expression, and oxidative stress. We and others recently
      identified a potential deleterious role of dietary fructose in the generation of
      tubulointerstitial injury and the acceleration of CKD. In this study, we
      investigated the potential role of endogenous fructose production, as opposed to
      dietary fructose, and its metabolism through fructokinase in the development of
      diabetic nephropathy. Wild-type mice with streptozotocin-induced diabetes
      developed proteinuria, reduced GFR, and renal glomerular and proximal tubular
      injury. Increased renal expression of aldose reductase; elevated levels of renal
      sorbitol, fructose, and uric acid; and low levels of ATP confirmed activation of
      the fructokinase pathway. Furthermore, renal expression of inflammatory cytokines
      with macrophage infiltration was prominent. In contrast, diabetic fructokinase
      deficient mice demonstrated significantly less proteinuria, renal dysfunction,
      renal injury, and inflammation. These studies identify fructokinase as a novel
      mediator of diabetic nephropathy and document a novel role for endogenous
      fructose production, or fructoneogenesis, in driving renal disease. 

PMID- 24876115
TI  - CKD and the risk of incident cancer.
AB  - Previous studies report a higher risk of cancer in patients with ESRD, but the
      impact of less severe CKD on risk of cancer is uncertain. Our objective was to
      evaluate the association between level of kidney function and subsequent cancer
      risk. We performed a retrospective cohort study of 1,190,538 adults who were
      receiving care within a health care delivery system, had a measurement of kidney
      function obtained between 2000 and 2008, and had no prior cancer. We examined the
      association between level of eGFR and the risk of incident cancer; the primary
      outcome was renal cancer, and secondary outcomes were any cancer and specific
      cancers (urothelial, prostate, breast, lung, and colorectal). During 6,000,420
      person-years of follow-up, we identified 76,809 incident cancers in 72,875
      subjects. After adjustment for time-updated confounders, lower eGFR (in
      milliliters per minute per 1.73 m(2)) was associated with an increased risk of
      renal cancer (adjusted hazard ratio [HR], 1.39; 95% confidence interval [95% CI],
      1.22 to 1.58 for eGFR=45-59; HR, 1.81; 95% CI, 1.51 to 2.17 for eGFR=30-44; HR,
      2.28; 95% CI, 1.78 to 2.92 for eGFR<30). We also observed an increased risk of
      urothelial cancer at eGFR<30 but no significant associations between eGFR and
      prostate, breast, lung, colorectal, or any cancer overall. In conclusion, reduced
      eGFR is associated with an independently higher risk of renal and urothelial
      cancer but not other cancer types. 

PMID- 24876116
TI  - A homozygous missense mutation in the ciliary gene TTC21B causes familial FSGS.
AB  - Several genes, mainly involved in podocyte cytoskeleton regulation, have been
      implicated in familial forms of primary FSGS. We identified a homozygous missense
      mutation (p.P209L) in the TTC21B gene in seven families with FSGS. Mutations in
      this ciliary gene were previously reported to cause nephronophthisis, a chronic
      tubulointerstitial nephropathy. Notably, tubular basement membrane thickening
      reminiscent of that observed in nephronophthisis was present in patients with
      FSGS and the p.P209L mutation. We demonstrated that the TTC21B gene product
      IFT139, an intraflagellar transport-A component, mainly localizes at the base of
      the primary cilium in developing podocytes from human fetal tissue and in
      undifferentiated cultured podocytes. In contrast, in nonciliated adult podocytes
      and differentiated cultured cells, IFT139 relocalized along the extended
      microtubule network. We further showed that knockdown of IFT139 in podocytes
      leads to primary cilia defects, abnormal cell migration, and cytoskeleton
      alterations, which can be partially rescued by p.P209L overexpression, indicating
      its hypomorphic effect. Our results demonstrate the involvement of a ciliary gene
      in a glomerular disorder and point to a critical function of IFT139 in podocytes.
      Altogether, these data suggest that this homozygous TTC21B p.P209L mutation leads
      to a novel hereditary kidney disorder with both glomerular and tubulointerstitial
      damages. 

PMID- 24876117
TI  - Sequencing of LRP2 reveals multiple rare variants associated with urinary trefoil
      factor-3.
AB  - Novel biomarkers are being investigated to identify patients with kidney disease.
      We measured a panel of 13 urinary biomarkers in participants from the Offspring
      Cohort of the Framingham Heart Study. Using an Affymetrix chip with imputation to
      2.5 M single-nucleotide polymorphisms (SNPs), we conducted a GWAS of these
      biomarkers (n=2640) followed by exonic sequencing and genotyping. Functional
      studies in zebrafish were used to investigate histologic correlation with renal
      function. Across all 13 biomarkers, there were 97 significant SNPs at three loci.
      Lead SNPs at each locus were rs6555820 (P=6.7*10(-49); minor allele frequency
      [MAF]=0.49) in HAVCR1 (associated with kidney injury molecule-1), rs7565788
      (P=2.15*10(-16); MAF=0.22) in LRP2 (associated with trefoil factor 3 [TFF3]), and
      rs11048230 (P=4.77*10(-8); MAF=0.10) in an intergenic region near RASSF8
      (associated with vascular endothelial growth factor). Validation in the CKDGen
      Consortium (n=67,093) showed that only rs7565788 at LRP2, which encodes megalin,
      was associated with eGFR (P=0.003). Sequencing of exons 16-72 of LRP2 in 200
      unrelated individuals at extremes of urinary TFF3 levels identified 197 variants
      (152 rare; MAF<0.05), 31 of which (27 rare) were nonsynonymous. In aggregate
      testing, rare variants were associated with urinary TFF3 levels (P=0.003), and
      the lead GWAS signal was not explained by these variants. Knockdown of LRP2 in
      zebrafish did not alter the renal phenotype in static or kidney injury models. In
      conclusion, this study revealed common variants associated with urinary levels of
      TFF3, kidney injury molecule-1, and vascular endothelial growth factor and
      identified a cluster of rare variants independently associated with TFF3.

PMID- 24876118
TI  - The seen and the unseen: clinical guidelines and cost-effective care.

PMID- 24876119
TI  - Sweet debate: fructose versus glucose in diabetic kidney disease.

PMID- 24876120
TI  - The Kidney Disease Screening and Awareness Program (KDSAP): a novel translatable
      model for increasing interest in nephrology careers.
AB  - Despite the increasing prevalence of CKD in the United States, there is a
      declining interest among United States medical graduates in nephrology as a
      career choice. Effective programs are needed to generate interest at early
      educational stages when career choices can be influenced. The Kidney Disease
      Screening and Awareness Program (KDSAP) is a novel program initiated at Harvard
      College that increases student knowledge of and interest in kidney health and
      disease, interest in nephrology career paths, and participation in kidney disease
      research. This model, built on physician mentoring, kidney screening of
      underserved populations, direct interactions with kidney patients, and
      opportunities to participate in kidney research, can be reproduced and translated
      to other workforce-challenged subspecialties. 

PMID- 24876124
TI  - Rate-constrained 3D surface estimation from noise-corrupted multiview depth
      videos.
AB  - Transmitting compactly represented geometry of a dynamic 3D scene from a sender
      can enable a multitude of imaging functionalities at a receiver, such as
      synthesis of virtual images at freely chosen viewpoints via depth-image-based
      rendering. While depth maps-projections of 3D geometry onto 2D image planes at
      chosen camera viewpoints-can nowadays be readily captured by inexpensive depth
      sensors, they are often corrupted by non-negligible acquisition noise. Given
      depth maps need to be denoised and compressed at the encoder for efficient
      network transmission to the decoder, in this paper, we consider the denoising and
      compression problems jointly, arguing that doing so will result in a better
      overall performance than the alternative of solving the two problems separately
      in two stages. Specifically, we formulate a rate-constrained estimation problem,
      where given a set of observed noise-corrupted depth maps, the most probable
      (maximum a posteriori (MAP)) 3D surface is sought within a search space of
      surfaces with representation size no larger than a prespecified rate constraint.
      Our rate-constrained MAP solution reduces to the conventional unconstrained MAP
      3D surface reconstruction solution if the rate constraint is loose. To solve our
      posed rate-constrained estimation problem, we propose an iterative algorithm,
      where in each iteration the structure (object boundaries) and the texture
      (surfaces within the object boundaries) of the depth maps are optimized
      alternately. Using the MVC codec for compression of multiview depth video and
      MPEG free viewpoint video sequences as input, experimental results show that rate
      constrained estimated 3D surfaces computed by our algorithm can reduce coding
      rate of depth maps by up to 32% compared with unconstrained estimated surfaces
      for the same quality of synthesized virtual views at the decoder.

PMID- 24876122
TI  - Dysfunction of intraflagellar transport proteins beyond the primary cilium.

PMID- 24876123
TI  - CKD and risk of renal cell carcinoma: a causal association?

PMID- 24876125
TI  - Progressive image denoising.
AB  - Image denoising continues to be an active research topic. Although state-of-the
      art denoising methods are numerically impressive and approch theoretical limits,
      they suffer from visible artifacts.While they produce acceptable results for
      natural images, human eyes are less forgiving when viewing synthetic images. At
      the same time, current methods are becoming more complex, making analysis, and
      implementation difficult. We propose image denoising as a simple physical
      process, which progressively reduces noise by deterministic annealing. The
      results of our implementation are numerically and visually excellent. We further
      demonstrate that our method is particularly suited for synthetic images. Finally,
      we offer a new perspective on image denoising using robust estimators.

PMID- 24876126
TI  - Complex background subtraction by pursuing dynamic spatio-temporal models.
AB  - Although it has been widely discussed in video surveillance, background
      subtraction is still an open problem in the context of complex scenarios, e.g.,
      dynamic backgrounds, illumination variations, and indistinct foreground objects.
      To address these challenges, we propose an effective background subtraction
      method by learning and maintaining an array of dynamic texture models within the
      spatio-temporal representations. At any location of the scene, we extract a
      sequence of regular video bricks, i.e., video volumes spanning over both spatial
      and temporal domain. The background modeling is thus posed as pursuing subspaces
      within the video bricks while adapting the scene variations. For each sequence of
      video bricks, we pursue the subspace by employing the auto regressive moving
      average model that jointly characterizes the appearance consistency and temporal
      coherence of the observations. During online processing, we incrementally update
      the subspaces to cope with disturbances from foreground objects and scene
      changes. In the experiments, we validate the proposed method in several complex
      scenarios, and show superior performances over other state-of-the-art approaches
      of background subtraction. The empirical studies of parameter setting and
      component analysis are presented as well.

PMID- 24876121
TI  - Reduced renal calcium excretion in the absence of sclerostin expression: evidence
      for a novel calcium-regulating bone kidney axis.
AB  - The kidneys contribute to calcium homeostasis by adjusting the reabsorption and
      excretion of filtered calcium through processes that are regulated by parathyroid
      hormone (PTH) and 1alpha,25-dihydroxyvitamin D3 (1alpha,25[OH]2D3). Most of the
      filtered calcium is reabsorbed in the proximal tubule, primarily by paracellular
      mechanisms that are not sensitive to calcium-regulating hormones in
      physiologically relevant ways. In the distal tubule, however, calcium is
      reabsorbed by channels and transporters, the activity or expression of which is
      highly regulated and increased by PTH and 1alpha,25(OH)2D3. Recent research
      suggests that other, heretofore unrecognized factors, such as the osteocyte
      specific protein sclerostin, also regulate renal calcium excretion. Clues in this
      regard have come from the study of humans and mice with inactivating mutations of
      the sclerostin gene that both have increased skeletal density, which would
      necessitate an increase in intestinal absorption and/or renal reabsorption of
      calcium. Deletion of the sclerostin gene in mice significantly diminishes urinary
      calcium excretion and increases fractional renal calcium reabsorption. This is
      associated with increased circulating 1alpha,25(OH)2D3 levels, whereas sclerostin
      directly suppresses 1alpha-hydroxylase in immortalized proximal tubular cells.
      Thus, evidence is accumulating that sclerostin directly or indirectly reduces
      renal calcium reabsorption, suggesting the presence of a novel calcium-excreting
      bone-kidney axis. 

PMID- 24876127
TI  - Coordinated control of senescence by lncRNA and a novel T-box3 co-repressor
      complex.
AB  - Cellular senescence is a crucial tumor suppressor mechanism. We discovered a
      CAPERalpha/TBX3 repressor complex required to prevent senescence in primary cells
      and mouse embryos. Critical, previously unknown roles for CAPERalpha in
      controlling cell proliferation are manifest in an obligatory interaction with
      TBX3 to regulate chromatin structure and repress transcription of CDKN2A-p16INK
      and the RB pathway. The IncRNA UCA1 is a direct target of CAPERalpha/TBX3
      repression whose overexpression is sufficient to induce senescence. In
      proliferating cells, we found that hnRNPA1 binds and destabilizes CDKN2A-p16INK
      mRNA whereas during senescence, UCA1 sequesters hnRNPA1 and thus stabilizes
      CDKN2A-p16INK. Thus CAPERalpha/TBX3 and UCA1 constitute a coordinated,
      reinforcing mechanism to regulate both CDKN2A-p16INK transcription and mRNA
      stability. Dissociation of the CAPERalpha/TBX3 co-repressor during oncogenic
      stress activates UCA1, revealing a novel mechanism for oncogene-induced
      senescence. Our elucidation of CAPERalpha and UCA1 functions in vivo provides new
      insights into senescence induction, and the oncogenic and developmental
      properties of TBX3. 

PMID- 24876128
TI  - TAF7L modulates brown adipose tissue formation.
AB  - Brown adipose tissue (BAT) plays an essential role in metabolic homeostasis by
      dissipating energy via thermogenesis through uncoupling protein 1 (UCP1).
      Previously, we reported that the TATA-binding protein associated factor 7L
      (TAF7L) is an important regulator of white adipose tissue (WAT) differentiation.
      In this study, we show that TAF7L also serves as a molecular switch between brown
      fat and muscle lineages in vivo and in vitro. In adipose tissue, TAF7L-containing
      TFIID complexes associate with PPARgamma to mediate DNA looping between distal
      enhancers and core promoter elements. Our findings suggest that the presence of
      the tissue-specific TAF7L subunit in TFIID functions to promote long-range
      chromatin interactions during BAT lineage specification. 

PMID- 24876130
TI  - 3-D flexible nano-textured high-density microelectrode arrays for high
      performance neuro-monitoring and neuro-stimulation.
AB  - We introduce a new 3-D flexible microelectrode array for high performance
      electrographic neural signal recording and stimulation. The microelectrode
      architecture maximizes the number of channels on each shank and minimizes its
      footprint. The electrode was implemented on flexible polyimide substrate using
      microfabrication and thin-film processing. The electrode has a planar layout and
      comprises multiple shanks. Each shank is three mm in length and carries six gold
      pads representing the neuro-interfacing channels. The channels are used in
      recording important precursors with potential clinical relevance and consequent
      electrical stimulation to perturb the clinical condition. The polyimide structure
      satisfied the mechanical characteristics required for the proper electrode
      implantation and operation. Pad postprocessing technique was developed to improve
      the electrode electrical performance. The planar electrodes were used for
      creating 3-D "Waterloo Array" microelectrode with controlled gaps using custom
      designed stackers. Electrode characterization and benchmarking against commercial
      equivalents demonstrated the superiority of the Flex electrodes. The Flex and
      commercial electrodes were associated with low-power implantable responsive neuro
      stimulation system. The electrodes performance in recording and stimulation
      application was quantified through in vitro and in vivo acute and chronic
      experiments on human brain slices and freely-moving rodents. The Flex electrodes
      exhibited remarkable drop in the electric impedance (100 times at 100 Hz),
      improved electrode-electrolyte interface noise (dropped by four times) and higher
      signal-to-noise ratio (3.3 times). 

PMID- 24876131
TI  - Cross-comparison of three electromyogram decomposition algorithms assessed with
      experimental and simulated data.
AB  - The reliability of clinical and scientific information provided by algorithms
      that automatically decompose the electromyogram (EMG) depends on the algorithms'
      accuracies. We used experimental and simulated data to assess the agreement and
      accuracy of three publicly available decomposition algorithms-EMGlab (McGill ,
      2005) (single channel data only), Fuzzy Expert (Erim and Lim, 2008) and Montreal
      (Florestal , 2009). Data consisted of quadrifilar needle EMGs from the tibialis
      anterior of 12 subjects at 10%, 20% and 50% maximum voluntary contraction (MVC);
      single channel needle EMGs from the biceps brachii of 10 controls and 10 patients
      during contractions just above threshold; and matched simulated data. Performance
      was assessed via agreement between pairs of algorithms for experimental data and
      accuracy with respect to the known decomposition for simulated data. For the
      quadrifilar experimental data, median agreements between the Montreal and Fuzzy
      Expert algorithms at 10%, 20%, and 50% MVC were 95%, 86%, and 64%, respectively.
      For the single channel control and patient data, median agreements between the
      three algorithm pairs were statistically similar at ~ 97% and ~ 92%,
      respectively. Accuracy on the simulated data exceeded this performance.
      Agreement/accuracy was strongly related to the Decomposability Index (Florestal ,
      2009). When agreement was high between algorithm pairs applied to simulated data,
      so was accuracy.

PMID- 24876129
TI  - Cyclin D activates the Rb tumor suppressor by mono-phosphorylation.
AB  - The widely accepted model of G1 cell cycle progression proposes that cyclin
      D:Cdk4/6 inactivates the Rb tumor suppressor during early G1 phase by progressive
      multi-phosphorylation, termed hypo-phosphorylation, to release E2F transcription
      factors. However, this model remains unproven biochemically and the biologically
      active form(s) of Rb remains unknown. In this study, we find that Rb is
      exclusively mono-phosphorylated in early G1 phase by cyclin D:Cdk4/6. Mono
      phosphorylated Rb is composed of 14 independent isoforms that are all targeted by
      the E1a oncoprotein, but show preferential E2F binding patterns. At the late G1
      Restriction Point, cyclin E:Cdk2 inactivates Rb by quantum hyper-phosphorylation.
      Cells undergoing a DNA damage response activate cyclin D:Cdk4/6 to generate mono
      phosphorylated Rb that regulates global transcription, whereas cells undergoing
      differentiation utilize un-phosphorylated Rb. These observations fundamentally
      change our understanding of G1 cell cycle progression and show that mono
      phosphorylated Rb, generated by cyclin D:Cdk4/6, is the only Rb isoform in early
      G1 phase. 

PMID- 24876132
TI  - Enhanced effective connectivity in mild occipital stroke patients with
      hemianopia.
AB  - Plasticity-based spontaneous recovery and rehabilitation intervention of stroke
      induced hemianopia have drawn great attention in recent years. However, the
      underlying neural mechanism remains unknown. This study aims to investigate brain
      network disruption and reorganization in hemianopia patients due to mild
      occipital stroke. Resting-state networks were constructed from 12 hemianopia
      patients with right occipital infarct by partial directed coherence analysis of
      multi-channel electroencephalograms. Compared with control subjects, the patients
      presented enhanced connectivity owing to newly formed connections. Compensational
      connections mostly originated from the peri-infarct area and targeted
      contralesional frontal, central, and parietal cortices. These new ipsilesional-to
      contralesional inter-hemispheric connections coordinately presented significant
      correlation with the extent of vision loss. The enhancement of connectivity might
      be the neural substrate for brain plasticity in stroke-induced hemianopia and may
      shed light on plasticity-based recovery or rehabilitation. 

PMID- 24876133
TI  - Automated detection of sleep apnea and hypopnea events based on robust airflow
      envelope tracking in the presence of breathing artifacts.
AB  - The paper presents a new approach to detection of apnea/hypopnea events, in the
      presence of artifacts and breathing irregularities, from a single-channel airflow
      record. The proposed algorithm, based on a robust envelope detector, identifies
      segments of signal affected by a high amplitude modulation corresponding to
      apnea/hypopnea events. It is shown that a robust airflow envelope-free of
      breathing artifacts-improves effectiveness of the diagnostic process and allows
      one to localize the beginning and the end of each episode more accurately. The
      performance of the proposed approach, evaluated on 30 overnight polysomnographic
      recordings, was assessed using diagnostic measures such as accuracy, sensitivity,
      specificity, and Cohen's coefficient of agreement; the achieved levels were equal
      to 95%, 90%, 96%, and 0.82, respectively. The results suggest that the algorithm
      may be implemented successfully in portable monitoring devices, as well as in
      software-packages used in sleep laboratories for automated evaluation of sleep
      apnea/hypopnea syndrome.

PMID- 24876134
TI  - Simulation-based scenario-specific channel modeling for WBAN cooperative
      transmission schemes.
AB  - Wireless body area networks (WBANs) are an emerging technology for realizing
      efficient healthcare and remote medicine for the aging society of the future. In
      order to improve the reliability of WBAN systems and support its various
      applications, channel modeling and performance evaluation are important. This
      paper proposes a simulation-based channel modeling for evaluating the performance
      of WBAN cooperative transmission schemes. The time series of path losses among
      seven on-body nodes are generated by the finite-difference time-domain method for
      seven body motions. The statistical parameters of the path loss for all the
      motions are also obtained. The generated path loss is then applied to the
      evaluation of the two-hop decode-and-forward relaying scheme, yielding an
      improvement in transmit power. From the evaluation of body motion, useful
      insights are obtained such as which relay links are more robust than others.
      Finally, the proposed approach is validated through comparison with a measurement
      based approach. 

PMID- 24876135
TI  - Electromagnetic respiratory effort harvester: human testing and metabolic cost
      analysis.
AB  - Remote health monitoring is increasingly recognized as a valuable tool in chronic
      disease management. Continuous respiratory monitoring could be a powerful tool in
      managing chronic diseases, however it is infrequently performed because of
      obtrusiveness and inconvenience of the existing methods. The movements of the
      chest wall and abdominal area during normal breathing can be monitored and
      harvested to enable self-powered wearable biosensors for continuous remote
      monitoring. This paper presents human testing results of a light-weight (30 g),
      wearable respiratory effort energy harvesting sensor. The harvester output
      voltage, power, and its metabolic burden, are measured on twenty subjects in two
      resting and exercise conditions each lasting 5 min. The system includes two off
      the-shelf miniature electromagnetic generators harvesting and sensing thoracic
      and abdominal movements. Modules can be placed in series to increase the output
      voltage for rectification purposes. Electromagnetic respiratory effort
      harvester/sensor system can produce up to 1.4 V, 6.44 mW, and harvests 30.4 mJ
      during a 5-min exercise stage. A statistical paired t-test analysis of the
      calculated EE confirmed there is no significant change ( P > 0.05 ) in the
      metabolic rate of subjects wearing the electromagnetic harvester and biosensor.

PMID- 24876136
TI  - MyHealthAssistant: an event-driven middleware for multiple medical applications
      on a smartphone-mediated body sensor network.
AB  - An ever-growing range of wireless sensors for medical monitoring has shown that
      there is significant interest in monitoring patients in their everyday
      surroundings. It however remains a challenge to merge information from several
      wireless sensors and applications are commonly built from scratch. This paper
      presents a middleware targeted for medical applications on smartphone-like
      platforms that relies on an event-based design to enable flexible coupling with
      changing sets of wireless sensor units, while posing only a minor overhead on the
      resources and battery capacity of the interconnected devices. We illustrate the
      requirements for such middleware with three different healthcare applications
      that were deployed with our middleware solution, and characterize the performance
      with energy consumption, overhead caused for the smartphone, and processing time
      under real-world circumstances. Results show that with sensing-intensive
      applications, our solution only minimally impacts the phone's resources, with an
      added CPU utilization of 3% and a memory usage under 7 MB. Furthermore, for a
      minimum message delivery ratio of 99.9%, up to 12 sensor readings per second are
      guaranteed to be handled, regardless of the number of applications using our
      middleware. 

PMID- 24876137
TI  - [Quantitative PCR (qPCR) and the guide to good practices MIQE: adapting and
      relevance in the clinical biology context].
AB  - The qPCR has been introduced in clinical and biomedical research for over 10
      years from now. Its use in trials and diagnostics is continuously increasing. Due
      to this heavy use, the question of relyability and relevance of qPCR results has
      to be asked. This review proposes a documented and evidence based answer to this
      question, thanks to the MIQE (minimum information for publication of quantitative
      real-time PCR experiments) guideline. The whole analysis process is addressed,
      from nucleic acids extraction to data management. Simple answers are given,
      taking into account the technical constraints from clinical research in order to
      allow a realistic application of this guideline.

PMID- 24876138
TI  - [Complement deficiencies and human diseases].
AB  - The complement system is a complex system involving serum and membrane proteins
      interacting in a regulated manner. The complement system plays a major role in
      antibacterial immunity, in inflammation, and in immune complex processing.
      Therefore, deficiencies in complement proteins are associated with increased
      susceptibility to bacterial infections and autoimmune diseases. These
      deficiencies can be inherited or acquired. Most of them can be screened by simple
      laboratory tests but require a diagnosis in a specialized laboratory. All
      sequences of complement genes are known, and the discovery of a deficiency must
      lead to genetic testing. The discovery of a congenital deficiency requires a
      familial study and a prophylaxis. In this article, we review the complement
      cascade, the laboratory tests to explore it, and the main diseases associated
      with complement deficiencies. 

PMID- 24876139
TI  - [Immunogenetics of nasopharyngeal carcinoma].
AB  - Nasopharyngeal carcinoma (NPC) is a complex multifactorial disorder involving
      both genetic and environmental factors. Genetic predisposition linked to the
      immune system has been associated with various tumors. This involves genetic
      diversity of the genes encoding the molecules of the immune response such as
      inflammation and anti-tumor surveillance. In this work, we examined the impact of
      the immunogenetic diversity on the risk of the NPC in different populations
      studied. These data show that the interindividual variability of the genetic
      regulation of immune processes increases the risk of NPC in individuals
      previously predisposed due to other risk factors (genetic / environmental). This
      synthesis, in addition to the predictive aspects, could provide innovative
      research for the development of new therapeutic approaches.

PMID- 24876140
TI  - [Changes of Von Willebrand factor concentration during pregnancy].
AB  - The multimeric glycoprotein Von Willebrand factor (vWF), is produced by vascular
      endothelium and platelet. If some constitutionals deficiencies leading to
      hemorrhagic syndrome have been explored in the literature, increased production
      of vWF observed during cellular distress and pregnancy have not been explored in
      our milieu. The aim of this study was to determine vWF changes during pregnancy
      in a group of Cameroonian women and find out the possibility of using it as a
      marker of fetal distress. Serum was collected from 46 women in the second and
      third trimesters of pregnancy. The determination of vWF concentration was
      performed using the Asserachrom vWF reagent: Ag (Diagnostica Stago, France). The
      average concentrations of vWF in the second and third trimester samples were
      respectively 215.47 +/- 9.38% (UI/dL) and 264.09 +/- 11.58% (UI/dL). The
      difference between (i) concentrations of vWF during the second and third
      trimester of pregnancy was statistically significant (P-value<0.0001); (ii)
      concentrations of vWF according to mother's ages was not significant; (iii)
      concentrations of vWF in blood group O and B women was statistically significant
      (P-value<0.05). We observed a difference between vWF values in women whose babies
      had Apgar score 4 to 6 compared to those with Apgar score between 7 and 10. The
      different was not statistically significant probably due to low effective. In
      conclusion, vWF production during the pregnancy varies with gestational age and
      maternal blood group. It may increases during fetal distress. 

PMID- 24876141
TI  - [Hemolysis influence on twenty-two biochemical parameters measurement].
AB  - The study of the influence of hemolysis was determined experimentally for twenty
      two biochemical parameters on the analyzer Cobas 6000 ce (Roche Diagnostics). The
      addition method of hemolysate was used to create an increasing concentration of
      hemoglobin ranging from 0 to 2000 MUmol/L. The limit of 10% variation was chosen
      to define the influence of hemolysis on the measurement. The parameters studied
      were classified into several categories: the parameters for which hemolysis does
      not influence the measurement: albumin, uric acid, calcium, C-reactive protein,
      myoglobin, NT -pro BNP, S100 protein, and urea; parameters impacted positively
      leading to an overestimation of the result: aspartate aminotransferase, total
      cholesterol, creatine kinase, creatinine, lactate dehydrogenase, magnesium,
      magnesium, total protein, triglycerides; and negatively impacted settings so
      causing an underestimation of the result: alanine amino- transferase, gamma
      glutamyl transferase, lipase, alkaline phosphatase, troponin T hypersensitive.
      Certain parameters influence of hemolysis varies depending on the magnitude of
      the measured parameter this interference being observed for normal values but
      disappearing for pathological values: creatinine, cholesterol, alkaline
      phosphatase, triglycerides, or the inverse interference is greater than for
      conventional pathological values: lipase, alanine amino-transferase. Knowledge of
      this variability interference allows the biologist to adapt its methods of
      reporting in the case of haemolysed samples.

PMID- 24876142
TI  - [Development and analytical validation according COFRAC recommendations of
      pyruvate and ketone body assay on open automated analyser].
AB  - Measurements of pyruvate and ketones bodies (acetoacetate and 3-hydroxybutyrate)
      are essential to the investigation of intermediary metabolism. Indeed, their
      blood levels reflect energy balance influenced by nutritional status. This
      balance can be disturbed in certain diseases such as diabetes and some inherited
      metabolic disorders. We have developed methods for assays on open automated
      biochemistry analyser, Konelab 20 XT (ThermoFischer, Whaltham USA), using kits
      marketed by Sobioda (Montbonnot, France) for pyruvate and Wako Chemicals GmbH
      (Neuss, Germany) for ketones, on deproteinised blood sample. We have validated
      the performance of these three quantitative methods using NF EN ISO 15189 (range
      B) standard criteria. We obtain satisfactory results concerning fidelity
      (precision measured as within and between batch CVs are respectively less than 7%
      and less than 6%), measuring ranges (from 7.7 to 228 MUmol/L for pyruvate and
      from 22.6 to 650 MUM for total ketone bodies), accuracy (10.4 MUmol/L in
      physiological range for pyruvate and 7.1 MUmol/L for 3-hydroxybutyrate) and
      comparing methods (versus manual assay with spectrophotometry on Uvikon XL).
      Establishment of reference ranges (35 to 74 MUmol/L for pyruvate, less than 100
      MUM for 3-hydroxybutyrate and less than 44 MUmol/L for acetoacetate) and reagents
      stability study (up to 12 weeks if frozen) have enabled us to finalize method
      validation and to add these assays to our routine laboratory repertoire.

PMID- 24876143
TI  - [ADAMTS13 and thrombotic thrombocytopenic purpura retrospective study at the
      hospital of Le Mans].
AB  - Thrombotic thrombocytopenic purpura (TTP) is a rare disease with poor prognosis
      in the absence of treatment. The aim of the study was to compare with the
      literature, the clinical, biological and therapeutic management of PTT at the
      hospital of Le Mans (CHM) and to identify sub groups. The criteria for inclusion
      were all patients hospitalized between 2006 and 2012 at CHM with a number of
      platelets, level of hemoglobin and ADAMTS13 activity respectively less than 150
      G/L, 110 g/L and 10 %. Eleven patients were included, confirming the
      epidemiological level rarity of this disease and the prevalence in young women,
      with immune dysfunction, and Afro-Caribbean origin. Consistent with literature,
      patients had heterogeneous symptoms but mainly neurological symptoms. Biological
      results were heteregenous and also different from the diagnostic described by
      Amorosi. Concerning therapy, all patients underwent plasma exchange with fresh
      frozen plasma substitution, confirming this as a reference treatment of first
      intention. Sub-group analysis have highlighted three predictive factors of
      mortality which were: an age over 70 years of age, a renal failure and a
      haptoglobin level superior to 0.10 g/dL. This study reminded the clinical,
      biological and therapeutic recommendations about TTP and described predictive
      factors of mortality.

PMID- 24876144
TI  - Prevalence of Y chromosome microdeletions in infertile Tunisian men.
AB  - Yq microdeletions are the leading genetic cause of male infertility and its
      detection in clinically relevant for appropriate genetic counseling. The
      objective of this study was to determine the frequency of Y microdeletion in a
      group of Tunisian infertile men and to compare the prevalence of these
      abnormalities with other countries and other Tunisian reported series. Totally,
      105 Tunisian idiopathic infertile men (74 azoospermic and 31 severe
      oligozoospermic) were screened for the presence of Y chromosome microdeletions.
      The screening of Yq microdeletions was performed by two multiplex PCRs using six
      STS markers recommended by the EAA/EMQN. No microdeletions were detected in the
      men with severe oligozoospermia. In the azoospermic group, 2/74 (2.7%) patients
      showed Y chromosome microdeletions. Both had complete deletion of the AZFc
      region. No microdeletion was identified in the AZFa region or in the AZFb region.
      The estimated frequency of Y chromosome microdeletions in the present survey was
      similar to some other reports but lower than that of previous reports in Tunisian
      populations. 

PMID- 24876145
TI  - [Influence of anticoagulant on the plasma level of fifteen biochemical
      parameters].
AB  - The study of the influence of the anticoagulant used in blood collection tubes to
      obtain plasma was performed for fifteen biochemical parameters measured with
      automated Cobas 6000 (Roche Diagnostics). For each parameter tested the entire
      measurement domain was studied. The comparison of results obtained on plasma
      blood sample obtained by lithium heparin and EDTA include: correlation, the
      limits of acceptability in the standards of monitoring and interpretation
      standards regression defined by the SFBC and analysis of Bland-Altman. The
      parameters studied were classified into three categories. The parameters for
      which the assay is not influenced by the nature of the anticoagulant used:
      apolipoprotein A1, apolipoprotein B, alanine amino-transferase, creatine kinase,
      creatinine, total cholesterol, HDL-cholesterol, lipase, NT-Pro BNP, troponine T
      and urea. The parameters for which the results are underestimated EDTA plasma,
      including those for which the impact is moderate and for which the interpretive
      standards are not changed: triglycerides, and those for which performance
      standards are changed on one or more levels: aspartate aminotransferase and
      lactate dehydrogenase; and finally the not practicable EDTA plasma parameters:
      alkaline phosphatase.

PMID- 24876148
TI  - Paraneoplastic granulocytosis in an advanced lung cancer patient.
AB  - Paraneoplastic syndromes (PNPs) refer to cancer-associated signs and symptoms
      arising in organs and tissues that are remote from the cancer and unrelated to
      metastasis. Currently the best described PNPs are attributed to tumor secretion
      of functional peptides and hormones or immune cross-reactivity between tumor and
      normal host tissues. Paraneoplastic hematologic syndromes are observed more
      rarely. Here we report a case of paraneoplastic granulocytosis in an advanced
      lung cancer patient. 

PMID- 24876146
TI  - [Evolution of autoantibodies profile in systemic lupus erythematosus according to
      age and clinical manifestations].
AB  - Clinical features and auto-antibodies profile of 35 Senegalese patients'
      diagnosed systemic lupus erythematosus (SLE) were analyzed after measurement of
      antinuclear antibodies (ANA) by IFI, detection of Abs anti-DNA native by ELISA
      and evaluation of antibodies anti-Sm, anti-RNP, anti-SSA anti-SSB, anti-CCP2,
      anti-J0, and anti-Scl70 levels by immunodot. Mean age of 33 yrs (18-50 yrs) and
      sex ratio (F/M) of 16 were found. The most frequent clinical features were
      rheumatic (88.7%) and cutaneous (79.4%) disorders. ANA and anti-DNAn Abs were
      detected in 85.7% and 62.5% of the patients respectively. Abs anti-RNP, anti-Sm,
      anti-SSA, anti-SSB and anti-CCP2 were detected in 30 to 70% of patients. In young
      patients, the levels of anti-DNAn and anti-Sm Abs were higher than in patients
      older than 40 yrs (P<0.05). In addition, associations of cutaneous and rheumatic
      symptoms were characterized by high levels of anti-DNAn, anti-SSA and anti-SSB
      Abs. Our study shows the interest of a measurement of anti-DNAn, anti-SSA and
      anti-SSB Abs during the follow of SLE patients particularly in those presenting
      both rheumatic and cutaneous symptoms.

PMID- 24876147
TI  - [Chronic myeloid leukemia with variant e19a2 BCR-ABL1 fusion transcript: interest
      of the molecular identification at diagnosis for minimal residual disease follow
      up].
AB  - We report here the case of a sixty-eight-year old woman with chronic myeloid
      leukemia. Molecular techniques identified the presence of the rare e19a2 BCR-ABL1
      transcript. The patient was treated by 1(st) generation tyrosine-kinase inhibitor
      (TKI) (imatinib). Disease monitoring was performed by cytogenetic analyses and
      quantification of the BCR-ABL1 transcript. After 3 months, the treatment was
      modified due to an absence of biological response and poor tolerance. After 21
      months with 2nd generation TKIs (nilotinib), the patient was responding optimally
      to treatment, with a complete cytogenetic response and a major molecular
      response. This observation emphasizes the importance of determining the
      chromosomal breakpoints at diagnosis to enable adequate molecular monitoring of
      residual disease. Careful monitoring of minimal residual disease is important to
      thoroughly assess the response to treatment, detect resistance and adapt the
      therapeutic strategy. The kinetics and the depth of the response to TKI also
      represent major prognostic factors. Molecular monitoring is performed using real
      time quantitative PCR, which has to be adapted to each type of transcript. For
      rare BCR-ABL1 transcripts, an international standardization, as it is developed
      for conventional transcripts, is lacking. Yet, such a harmonization would be
      useful to assess in an optimal and large scale way the response to TKI in these
      patients, and to determine what the best management is. 

PMID- 24876149
TI  - [An adult patient with 49, XXXXY syndrome: further clinical and biological
      delineation].
AB  - 49, XXXXY syndrome is a rare sex chromosome aneuploidy occurring in 1:80 000
      1:100 000 male births. Data on this aneuploidy in adulthood are limited, with
      most of the literature data based on paediatric patients. We report a new male
      patient whose 49, XXXXY diagnosis was formally made at the age of 54 years. So
      far, no medical follow-up was performed specifically for his condition. This man
      presented with facial features (epicanthus, hypertelorism, up-slanting palpebral
      fissures), microorchidism and features of chronic hypoandrogenism with muscular
      weakness, sparse body hair, dry skin with abnormal healing of skin wounds.
      Endocrine evaluation confirmed a hypergonadotropic hypogonadism. He had moderate
      intellectual deficiency with more affected verbal skills. A recent deep vein
      thrombosis was diagnosed in his left leg. Unusually, in addition to moderate
      deafness, he developed progressively a severe vision impairment leading to
      blindness. There have been very few reports of adult individuals with 49, XXXXY
      syndrome and this kind of report may contribute to improved management of
      prospective medical healthcare associated with this condition in older
      individuals. 

PMID- 24876150
TI  - Schnitzler's syndrome; a case highlighting the complications of long-standing
      acquired autoinflammation.

PMID- 24876152
TI  - The role of the hepatocyte growth factor/c-MET pathway in pancreatic stellate
      cell-endothelial cell interactions: antiangiogenic implications in pancreatic
      cancer.
AB  - Activated cancer-associated human pancreatic stellate cells (CAhPSCs, which
      produce the collagenous stroma of pancreatic cancer [PC]) are known to play a
      major role in PC progression. Apart from inducing cancer cell proliferation and
      migration, CAhPSCs have also been implicated in neoangiogenesis in PC. However,
      the mechanisms mediating the observed angiogenic effects of CAhPSCs are unknown.
      A candidate pathway that may be involved in this process is the hepatocyte growth
      factor (HGF)/c-MET pathway and its helper molecule, urokinase-type plasminogen
      activator (uPA). This study investigated the effects of CAhPSC secretions on
      endothelial cell function in the presence and absence of HGF, c-MET and uPA
      inhibitors. HGF levels in CAhPSC secretions were quantified using ELISA. CAhPSC
      secretions were then incubated with human microvascular endothelial cells (HMEC
      1) and angiogenesis assessed by quantifying HMEC-1 tube formation and
      proliferation. CAhPSC-secreted HGF significantly increased HMEC-1 tube formation
      and proliferation; notably, these effects were downregulated by inhibition of
      HGF, its receptor c-MET and uPA. Phosphorylation of p38 mitogen-activated protein
      kinase was downregulated during inhibition of the HGF/c-MET pathway, whereas
      phosphatidylinositol-3 kinase and ERK1/2 remained unaffected. Our studies have
      shown for the first time that CAhPSCs induce proliferation and tube formation of
      HMEC-1 and that the HGF/c-MET pathway plays a major role in this induction. Given
      that standard antiangiogenic treatment targeting vascular endothelial growth
      factor has had limited success in the clinical setting, the findings of the
      current study provide strong support for a novel, alternative antiangiogenic
      approach targeting the HGF/c-MET and uPA pathways in PC. 

PMID- 24876151
TI  - Flavonoids from each of the six structural groups reactivate BRM, a possible
      cofactor for the anticancer effects of flavonoids.
AB  - Flavonoids have been extensively studied and are well documented to have
      anticancer effects, but it is not entirely known how they impact cellular
      mechanisms to elicit these effects. In the course of this study, we found that a
      variety of different flavonoids readily restored Brahma (BRM) in BRM-deficient
      cancer cell lines. Flavonoids from each of the six different structural groups
      were effective at inducing BRM expression as well as inhibiting growth in these
      BRM-deficient cancer cells. By blocking the induction of BRM with shRNA, we found
      that flavonoid-induced growth inhibition was BRM dependent. We also found that
      flavonoids can restore BRM functionality by reversing BRM acetylation. In
      addition, we observed that an array of natural flavonoid-containing products both
      induced BRM expression as well as deacetylated the BRM protein. We also tested
      two of the BRM-inducing flavonoids (Rutin and Diosmin) at both a low and a high
      dose on the development of tumors in an established murine lung cancer model. We
      found that these flavonoids effectively blocked development of adenomas in the
      lungs of wild-type mice but not in that of BRMnull mice. These data demonstrate
      that BRM expression and function are regulated by flavonoids and that functional
      BRM appears to be a prerequisite for the anticancer effects of flavonoids both in
      vitro and in vivo. 

PMID- 24876153
TI  - Protein tyrosine phosphatase receptor U (PTPRU) is required for glioma growth and
      motility.
AB  - The membrane protein tyrosine phosphatase receptor U (PTPRU) has been shown to
      function as a negative regulator of adhesion and proliferation in certain cancer
      cell types, primarily through its dephosphorylation of beta-catenin and
      inhibition of subsequent downstream signaling. In the present study, we set out
      to characterize the role of PTPRU in glioma and found that, while the expression
      of full-length PTPRU protein is low in these tumors, a number of non-full-length
      PTPRU isoforms are highly expressed. Among these isoforms, one in particular is
      localized to the nucleus, and its expression is increased in glioma tissues in a
      manner that positively correlates with malignancy grade. Short hairpin RNA
      knockdown of endogenous PTPRU in human and rat glioma cell lines suppressed
      proliferation, survival, invasion, migration, adhesion and vasculogenic tube
      formation in vitro, as well as intracranial tumor progression in vivo. In
      addition, knocking down PTPRU reduced tyrosine phosphorylation (pY) and
      transcriptional activity of beta-catenin, and we were able to specifically rescue
      the cell migration defect by expressing a LEF1-beta-catenin fusion protein in
      PTPRU-depleted cells. PTPRU knockdown also led to increased tyrosine pY of the E3
      ubiquitin ligase c-Cbl and to the destabilization of several focal adhesion
      proteins. Taken together, our findings demonstrate that endogenous PTPRU promote
      glioma progression through their effect on beta-catenin and focal adhesion
      signaling. 

PMID- 24876154
TI  - Purple urine bag syndrome.

PMID- 24876155
TI  - A patient with respiratory distress.

PMID- 24876157
TI  - Interleukin-8 is associated with acute and persistent dysfunction after optic
      neuritis.
AB  - BACKGROUND: Acute optic neuritis is often in association with multiple sclerosis
      (MS). Proinflammatory cytokines trigger neuronal damage in neuroinflammatory
      disorders but their role in optic neuritis is poorly investigated. OBJECTIVE: The
      objective of this work is to investigate the associations of intrathecal contents
      of proinflammatory cytokines with transient and persistent dysfunctions after
      optic neuritis. METHODS: In 50 MS patients followed for up to six months,
      cerebrospinal fluid (CSF) levels of IL-1beta, TNF and IL-8 were determined, along
      with clinical, neurophysiological and morphological measures of optic neuritis
      severity. RESULTS: Visual impairment, measured by high- and low-contrast visual
      acuity, and delayed visual-evoked potential (VEP) latencies were significantly
      correlated to IL-8 levels during optic neuritis. IL-8 at the time of optic
      neuritis was also associated with persistent demyelination and final axonal loss,
      inferred by VEP and optical coherence tomography measures, respectively. Contents
      of IL-8 were correlated to functional visual outcomes, being higher among
      patients with incomplete recovery. Multivariate analysis confirmed that IL-8
      significantly predicted final visual acuity, at equal values of demographics and
      baseline visual scores. CONCLUSION: Our study points to IL-8 as the main
      inflammatory cytokine associated with demyelination and secondary
      neurodegeneration in the optic nerve after optic neuritis.

PMID- 24876156
TI  - The effect of pelvic floor muscle training alone or in combination with
      electrostimulation in the treatment of sexual dysfunction in women with multiple
      sclerosis.
AB  - BACKGROUND: Sexual dysfunction (SD) affects up to 80% of multiple sclerosis (MS)
      patients and pelvic floor muscles (PFMs) play an important role in the sexual
      function of these patients. OBJECTIVES: The objective of this paper is to
      evaluate the impact of a rehabilitation program to treat lower urinary tract
      symptoms on SD of women with MS. METHODS: Thirty MS women were randomly allocated
      to one of three groups: pelvic floor muscle training (PFMT) with
      electromyographic (EMG) biofeedback and sham neuromuscular electrostimulation
      (NMES) (Group I), PFMT with EMG biofeedback and intravaginal NMES (Group II), and
      PFMT with EMG biofeedback and transcutaneous tibial nerve stimulation (TTNS)
      (Group III). Assessments, before and after the treatment, included: PFM function,
      PFM tone, flexibility of the vaginal opening and ability to relax the PFMs, and
      the Female Sexual Function Index (FSFI) questionnaire. RESULTS: After treatment,
      all groups showed improvements in all domains of the PERFECT scheme. PFM tone and
      flexibility of the vaginal opening was lower after the intervention only for
      Group II. All groups improved in arousal, lubrication, satisfaction and total
      score domains of the FSFI questionnaire. CONCLUSION: This study indicates that
      PFMT alone or in combination with intravaginal NMES or TTNS contributes to the
      improvement of SD.

PMID- 24876159
TI  - Retraction Notice.

PMID- 24876162
TI  - Generalized fixed drug eruption induced by tranexamic acid.

PMID- 24876160
TI  - P38alpha MAPK underlies muscular dystrophy and myofiber death through a Bax
      dependent mechanism.
AB  - Muscular dystrophies are a group of genetic diseases that lead to muscle wasting
      and, in most cases, premature death. Cytokines and inflammatory factors are
      released during the disease process where they promote deleterious signaling
      events that directly participate in myofiber death. Here, we show that p38alpha,
      a kinase in the greater mitogen-activated protein kinase (MAPK)-signaling
      network, serves as a nodal regulator of disease signaling in dystrophic muscle.
      Deletion of Mapk14 (p38alpha-encoding gene) in the skeletal muscle of mdx-
      (lacking dystrophin) or sgcd- (delta-sarcoglycan-encoding gene) null mice
      resulted in a significant reduction in pathology up to 6 months of age. We also
      generated MAPK kinase 6 (MKK6) muscle-specific transgenic mice to model
      heightened p38alpha disease signaling that occurs in dystrophic muscle, which
      resulted in severe myofiber necrosis and many hallmarks of muscular dystrophy.
      Mechanistically, we show that p38alpha directly induces myofiber death through a
      mitochondrial-dependent pathway involving direct phosphorylation and activation
      of the pro-death Bcl-2 family member Bax. Indeed, muscle-specific deletion of
      Bax, but not the apoptosis regulatory gene Tp53 (encoding p53), significantly
      reduced dystrophic pathology in the muscles of MKK6 transgenic mice. Moreover,
      use of a p38 MAPK pharmacologic inhibitor reduced dystrophic disease in Sgcd(-/-)
      mice suggesting a future therapeutic approach to delay disease. 

PMID- 24876161
TI  - Analysis of FMRP mRNA target datasets reveals highly associated mRNAs mediated by
      G-quadruplex structures formed via clustered WGGA sequences.
AB  - Fragile X syndrome, a common cause of intellectual disability and a well-known
      cause of autism spectrum disorder, is the result of loss or dysfunction of
      fragile X mental retardation protein (FMRP), a highly selective RNA-binding
      protein and translation regulator. A major research priority has been the
      identification of the mRNA targets of FMRP, particularly as recent studies
      suggest an excess of FMRP targets among genes implicated in idiopathic autism and
      schizophrenia. Several large-scale studies have attempted to identify mRNAs bound
      by FMRP through several methods, each generating a list of putative target genes,
      leading to distinct hypotheses by which FMRP recognizes its targets; namely, by
      RNA structure or sequence. However, no in depth analyses have been performed to
      identify the level of consensus among the studies. Here, we analyze four large
      FMRP target datasets to generate high-confidence consensus lists, and examine all
      datasets for sequence elements within the target RNAs to validate reported FMRP
      binding motifs (GACR, ACUK and WGGA). We found GACR to be highly enriched in FMRP
      datasets, while ACUK was not. The WGGA pattern was modestly enriched in several,
      but not all datasets. The previous association between FMRP and G-quadruplexes
      prompted the analysis of the distribution of WGGA in the target genes. Consistent
      with the requirements for G-quadruplex formation, we observed highly clustered
      WGGA motifs in FMRP targets compared with other genes, implicating both RNA
      structure and sequence in the recognition motif of FMRP. In addition, we generate
      a list of the top 40 FMRP targets associated with FXS-related phenotypes. 

PMID- 24876163
TI  - Continuation of all-trans retinoic acid despite the development of scrotal
      ulcerations in a black male.
AB  - Acute promyelocytic leukemia, an aggressive subtype of acute myeloid leukemia, is
      characterized by the t(15;17) translocation. Standard induction chemotherapy
      consists of (ATRA) in combination with anthracycline-based chemotherapy with or
      without the addition of cytarabine. Rare and serious side effects of ATRA have
      been reported including painful lip and scrotal ulcerations. Of 20 previous
      reports of genital ulceration, 17 patients had ATRA discontinued and
      corticosteroids initiated; however, the corticosteroid regimens and duration of
      therapy were not well described. Herein we present the first known case of a
      Black male with ATRA-associated scrotal ulcerations who was successfully managed
      with corticosteroids without cessation of all-trans retinoic acid. We report this
      case to highlight its rarity and to note that ATRA can be continued in
      combination with corticosteroids throughout induction.

PMID- 24876164
TI  - A controlled trial of photodynamic therapy of actinic keratosis comparing
      different red light sources.
AB  - BACKGROUND: Photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA) with red
      light is well established for actinic keratosis (AK). Differences have been
      observed concerning pain and efficacy rates with different red light sources.
      OBJECTIVES: To compare pain scores, short- and long-term efficacy rates of PDT of
      multiple AKs when employing different red light sources. MATERIAL AND METHODS: In
      a controlled trial, 88 patients (310 AK lesions) received ALA-PDT in combination
      with either visible light (VIS) + water-filtered infrared A (wIRA) light
      (PhotoDyn((r)) 750 (PD750), 580-1400 nm) for 30 min or incoherent light
      (Waldmann((r)) 1200L (Wa1200L), 600-720 nm) for 10-11 min. Follow-up visits were
      performed after 1, 3, 6, and 12 months. If there was no complete cure after 1, 3
      or 6 months, a second cycle of PDT was performed. RESULTS: Pain scores were
      significantly lower in patients illuminated with PD750 rather than Wa1200L.
      Patient complete clearance rates were 85% and 91% after 1 month, 79% and 92%
      after 3 months, 97% and 92% after 6 months, and 69% and 85% after 12 months in
      the PD750 and Wa1200L groups, respectively. Lesion complete clearance rates were
      94% and 92% after 1 month, 88% and 97% after 3 months, 96% and 95% after 6
      months, and 81% and 89% after 12 months in the PD750 and Wa1200L group,
      respectively. The efficacy rates were not significantly different. CONCLUSION: A
      VIS + wIRA light source produced considerably less pain, while efficacy was not
      much affected in contrast to previously published studies, probably because the
      illumination time was longer in this study.

PMID- 24876165
TI  - Preventing postpartum depression in a pediatric primary care clinic: a pilot
      study.

PMID- 24876166
TI  - Acute peripheral unilateral facial nerve paralysis following minor surgery.

PMID- 24876167
TI  - Rapid systematic review of repeated application of the epley maneuver for
      treating posterior BPPV.
AB  - OBJECTIVE: To evaluate the effect of repeated application of the Epley maneuver
      on patient-reported symptom relief and resolution of nystagmus in patients with
      posterior benign paroxysmal positional vertigo (p-BPPV). DATA SOURCES: PubMed,
      Embase, and the Cochrane Library. METHODS: A systematic search was conducted.
      Studies reporting original study data were included. Relevance and risk of bias
      (RoB) of the selected articles were assessed. Studies with low relevance, high
      RoB, or both were excluded. Success percentages and mean values were extracted.
      RESULTS: A total of 955 unique studies were retrieved. Fourteen of these
      satisfied the eligibility criteria. All of the included studies carried a high
      relevance and a moderate RoB. The majority of studies were 1-armed trials, in
      which the Epley was repeated only in case previous attempt(s) had failed. The
      maneuver was not repeated if it was successful. In 32% to 90% of patients, the
      first treatment session was successful. Reported cumulative success percentages
      ranged from 40% to 100% after the second session, 67% to 98% after the third
      session, 87% to 100% after the fourth session, and 100% in the studies in which
      patients received 5 sessions. One study evaluating the effect of multiple
      maneuvers in a single session showed a rise in success percentages from 84% for 1
      maneuver to 90% after 2 maneuvers and 92% after 3 maneuvers. CONCLUSION: Multiple
      studies with moderate RoB show a beneficial effect of multiple sessions of the
      Epley maneuver in p-BPPV patients who are not fully cleared of symptoms after the
      first session.

PMID- 24876168
TI  - [How do Cameroonian women experience their first gynecological examination? How
      can the procedure be modified to improve this experience?].
AB  - The gynecological examination is a key element in the diagnosis of the most
      genitourinary disorders. Improving how women experience the first gynecological
      examination (FGE) should have a significant impact on their perception of this
      examination and on their general feeling about it afterwards. OBJECTIVE: The aim
      of our study was to describe the general feeling of Cameroonian women towards the
      FGE and to identify the factors associated with negative feelings. METHODOLOGY:
      In this one-month survey study, we asked patients to complete a questionnaire
      about how they had experienced the FGE. The answers have been analyzed and the
      factors influencing the way they experience this examination determined. RESULTS:
      At the end of the FGE, 41.5% of the women had negative feelings, and 38.6%
      reported that the examination had been painful. The average age of women who
      experienced pain was younger than that of those who did not [19.4 vs 20.39 years,
      P = 0.029], as was that of women with negative feelings lower [19.41 vs 20.43
      years, P = 0.024]. A negative experience was significantly associated with a
      painful examination [P<=0.001], an examiner not specialized in gynecology [P =
      0.04], lack of information [P = 0.001], and lack of a separate room to undress [P
      = 0.038]. The rate of subsequent refusals of a gynecological examination was
      higher among women with a negative first experience [56.2% vs. 35.9%, P = 0.008].
      CONCLUSION: The FGE is experienced by Cameroonian women as very difficult. Their
      feelings at the end of this examination significantly influences their behavior
      towards gynecological examinations in general.

PMID- 24876169
TI  - [Intestinal cryptococcosis: an unusual presentation of disseminated
      cryptococcosis].
AB  - Cryptococcosis is a serious infection caused by an encapsulated yeast-like
      fungus, Cryptococcus neoformans. It is pathogenic most often in the lungs and
      central nervous system of immunocompromised patients. In this work we report an
      unusual localization of cryptococcosis in an HIV-infected patient. This rare
      localization was diagnosed from a stool sample sent to our laboratory for
      parasitological study. Direct examination of fresh stool showed the presence of
      many large, rounded thick-walled fungi. India ink staining of the stool showed
      encapsulated cryptococci, and C. neoformans was isolated by culture. Despite
      flucanazole treatment, the patient died. 

PMID- 24876170
TI  - Contact dermatitis to cobalt chloride with an unusual mechanism.
AB  - BACKGROUND: Contact dermatitis is a frequent inflammatory skin disease. A
      suspected diagnosis is based on clinical symptoms, a plausible contact to
      allergens and a suitable history of dermatitis. Therefore, careful diagnosis by
      patch testing is of great importance because the patch testing is important to
      find out which allergen/material causes the complaints. Metallic allergens such
      as cobalt are among the most common causes of allergic contact dermatitis, but
      frequencies of contact dermatitis to these allergens may vary in different skin
      areas. Here, we report an unusual case of cobalt allergy on the skin contact with
      the prosthetic leg of a 30-year-old female patient. CASE DESCRIPTION AND METHODS:
      The patient developed maculopapular and vesicular lesions on her contact region
      of residual limb to prosthetic leg. FINDINGS AND OUTCOME: She underwent standard
      patch testing, which resulted in a strong positive reaction to cobalt chloride.
      CONCLUSION: This case report may serve to remind doctors to be aware of potential
      allergic reactions to prostheses and to enable them to recognize a metal allergy
      if it appears. Prosthetists should also be reminded of potential allergic
      reactions. CLINICAL RELEVANCE: Cobalt can be used as an accelerator in making a
      prosthetic socket. Several cases have been reported concerning allergies to
      components of the prosthetic socket. This is the first report of sensitization to
      cobalt which is used in making a prosthetic leg.

PMID- 24876171
TI  - Depression and suicidality in COPD: understandable reaction or independent
      disorders?
AB  - Both depression and chronic obstructive pulmonary disease (COPD) are prevalent,
      severe and often comorbid disorders. There is a risk of undertreatment for
      depression in patients with COPD as depressive symptoms, including suicidal
      tendencies, can erroneously be conceptualised as an understandable reaction to
      COPD and not as signs of an independent depressive disorder. In this context, the
      comorbidity rates of COPD and depression, the risk of suicidal behaviour in
      patients with COPD, and the evidence base for pharmaco- and psychotherapy in
      these patients are reviewed. Because symptoms of depression and COPD overlap it
      remains unclear how far the prevalence of major depression in COPD exceeds that
      in the general population. The suicide risk appears to be increased in COPD.
      Methodological studies providing evidence for the antidepressant efficacy of
      antidepressants or psychotherapy in patients with COPD are lacking.
      Recommendations for clinicians on how to separate depression from an
      understandable reaction to COPD are provided. Given the profound effects of
      depression on quality of life, life expectancy, COPD prognosis and suicide risk
      it is important to carefully diagnose and treat depression in patients with COPD
      according to national guidelines. 

PMID- 24876172
TI  - Prolonged shedding of rhinovirus and re-infection in adults with respiratory
      tract illness.
AB  - Rhinovirus infections occur frequently throughout life and have been reported in
      about one-third of asymptomatic cases. The clinical significance of sequential
      rhinovirus infections remains unclear. To determine the incidence and clinical
      relevance of sequential rhinovirus detections, nasopharyngeal samples from 2485
      adults with acute cough/lower respiratory illness were analysed. Patients were
      enrolled prospectively by general practitioners from 12 European Union countries
      during three consecutive years (2007-2010). Nasopharyngeal samples were collected
      at the initial general practitioner consultation and 28 days thereafter and
      symptom scores were recorded by patients over that period. Rhinovirus RNA was
      detected in 444 (18%) out of 2485 visit one samples and in 110 (4.4%) out of 2485
      visit two respiratory samples. 21 (5%) of the 444 patients had both samples
      positive for rhinovirus. Genotyping of both virus detections was successful for
      17 (81%) out of 21 of these patients. Prolonged rhinovirus shedding occurred in
      six (35%) out of 21 and re-infection with a different rhinovirus in 11 (65%) out
      of 21. Rhinovirus re-infections were significantly associated with chronic
      obstructive pulmonary disease (p=0.04) and asthma (p=0.02) and appeared to be
      more severe than prolonged infections. Our findings indicate that in
      immunocompetent adults rhinovirus re-infections are more common than prolonged
      infections, and chronic airway comorbidities might predispose to more frequent
      rhinovirus re-infections. 

PMID- 24876174
TI  - Antifibrotic properties of epigallocatechin-3-gallate in endometriosis.
AB  - STUDY QUESTION: Is epigallocatechin-3-gallate (EGCG) treatment effective in the
      treatment of fibrosis in endometriosis? SUMMARY ANSWER: EGCG appears to have
      antifibrotic properties in endometriosis. WHAT IS KNOWN ALREADY: Histologically,
      endometriosis is characterized by dense fibrous tissue surrounding the
      endometrial glands and stroma. However, only a few studies to date have evaluated
      candidate new therapies for endometriosis-associated fibrosis. STUDY DESIGN,
      SIZE, DURATION: For this laboratory study, samples from 55 patients (45 with and
      10 without endometriosis) of reproductive age with normal menstrual cycles were
      analyzed. A total of 40 nude mice received single injection proliferative
      endometrial fragments from a total of 10 samples. PARTICIPANTS/MATERIALS,
      SETTING, METHODS: The in vitro effects of EGCG and N-acetyl-l-cysteine on
      fibrotic markers (alpha-smooth muscle actin, type I collagen, connective tissue
      growth factor and fibronectin) with and without transforming growth factor (TGF)
      beta1 stimulation, as well as on cell proliferation, migration and invasion and
      collagen gel contraction of endometrial and endometriotic stromal cells were
      evaluated by real-time PCR, immunocytochemistry, cell proliferation assays, in
      vitro migration and invasion assays and/or collagen gel contraction assays. The
      in vitro effects of EGCG on mitogen-activated protein kinase (MAPK) and Smad
      signaling pathways in endometrial and endometriotic stromal cells were evaluated
      by western blotting. Additionally, the effects of EGCG treatment on endometriotic
      implants were evaluated in a xenograft model of endometriosis in immunodeficient
      nude mice. MAIN RESULTS AND THE ROLE OF CHANCE: Treatment with EGCG significantly
      inhibited cell proliferation, migration and invasion of endometrial and
      endometriotic stromal cells from patients with endometriosis. In addition, EGCG
      treatment significantly decreased the TGF-beta1-dependent increase in the mRNA
      expression of fibrotic markers in both endometriotic and endometrial stromal
      cells. Both endometriotic and endometrial stromal cell-mediated contraction of
      collagen gels were significantly attenuated at 8, 12 and 24 h after treatment
      with EGCG. Epigallocatechin-3-gallate also significantly inhibited TGF-beta1
      stimulated activation of MAPK and Smad signaling pathways in endometrial and
      endometriotic stromal cells. Animal experiments showed that EGCG prevented the
      progression of fibrosis in endometriosis. LIMITATIONS, REASONS FOR CAUTION: The
      attractiveness of epigallocatechin-3-gallate as a drug candidate has been
      diminished by its relatively low bioavailability. However, numerous alterations
      to the EGCG molecule have been patented, either to improve the integrity of the
      native compound or to generate a more stable yet similarly efficacious molecule.
      Therefore, EGCG and its derivatives, analogs and prodrugs could potentially be
      developed into agents for the future treatment and/or prevention of
      endometriosis. WIDER IMPLICATIONS OF THE FINDINGS: Epigallocatechin-3-gallate is
      a potential drug candidate for the treatment and/or prevention of endometriosis.
      STUDY FUNDING/COMPETING INTERESTS: This study was supported in part by Karl Storz
      Endoscopy & GmbH (Tuttlingen, Germany). No competing interests are declared.

PMID- 24876173
TI  - The clinical and genetic features of COPD-asthma overlap syndrome.
AB  - Individuals with chronic obstructive pulmonary disease (COPD) and asthma are an
      important but poorly characterised group. The genetic determinants of COPD and
      asthma overlap have not been studied. The aim of this study was to identify
      clinical features and genetic risk factors for COPD and asthma overlap. Subjects
      were current or former smoking non-Hispanic whites or African-Americans with
      COPD. Overlap subjects reported a history of physician-diagnosed asthma before
      the age of 40 years. We compared clinical and radiographic features between COPD
      and overlap subjects. We performed genome-wide association studies (GWAS) in the
      non-Hispanic whites and African-American populations, and combined these results
      in a meta-analysis. More females and African-Americans reported a history of
      asthma. Overlap subjects had more severe and more frequent respiratory
      exacerbations, less emphysema and greater airway wall thickness compared to
      subjects with COPD alone. The non-Hispanic white GWAS identified single
      nucleotide polymorphisms in the genes CSMD1 (rs11779254, p=1.57 * 10(-6)) and
      SOX5 (rs59569785, p=1.61 * 10(-6)) and the meta-analysis identified single
      nucleotide polymorphisms in the gene GPR65 (rs6574978, p=1.18 * 10(-7))
      associated with COPD and asthma overlap. Overlap subjects have more
      exacerbations, less emphysema and more airway disease for any degree of lung
      function impairment compared to COPD alone. We identified novel genetic variants
      associated with this syndrome. COPD and asthma overlap is an important syndrome
      and may require distinct clinical management.

PMID- 24876175
TI  - Excess mortality in mothers of patients with polycystic ovary syndrome.
AB  - STUDY QUESTION: Do diabetic parents of patients with polycystic ovary syndrome
      (PCOS) encounter excess mortality compared with the mortality of men and women
      with type 2 diabetes, recruited without selection for PCOS? SUMMARY ANSWER: Type
      2 diabetes among mothers of PCOS patients results in excess mortality compared
      with women with diabetes from the general population. WHAT IS KNOWN ALREADY:
      Insulin resistance is a prominent feature of PCOS. Because of the heritable
      nature of PCOS, parents of these patients are also prone to develop type 2
      diabetes mellitus, which might influence their life expectancy. STUDY DESIGN,
      SIZE, DURATION: This reverse parent-offspring study included 946 mothers and 902
      fathers of patients with PCOS. PARTICIPANTS/MATERIALS, SETTING, METHODS: The
      medical history of the parents was primarily obtained during the initial
      screening of each patient and updated via questionnaires. Mortality data of these
      parents were compared with the mortality rates of the general Dutch population
      and with mortality rates of a control population consisting of 1353 men and women
      diagnosed with type 2 diabetes mellitus. The standardized mortality ratio (SMR)
      was calculated as the ratio of the observed mortality of the parents to the
      expected mortality in the general Dutch population. The mortality of parents with
      type 2 diabetes mellitus relative to controls with diabetes but not related to
      anyone with PCOS was standardized for age, gender and calendar period using
      Poisson regression. MAIN RESULTS AND ROLE OF CHANCE: In total, 302 parents were
      deceased in 62 693 person-years. Mothers above age 60 had a significant excess
      mortality of 1.50 (95% CI 1.15-1.92) compared with the general Dutch population.
      Moreover, mothers with diabetes had two-times higher mortality risk compared with
      control women with diabetes (RR 2.0, 95% CI 1.19-3.41). No excess mortality among
      fathers of PCOS patients was observed. LIMITATIONS, REASON FOR CAUTION: Although
      recall bias for family history was previously demonstrated to be minimal for long
      term chronic diseases, the prevalence of diabetes in the parents was based on
      their daughter's self-report and was not clinically confirmed. Also, no other
      additional clinical data regarding the parent population were available.
      Prospective long-term follow-up studies should be conducted to confirm this
      excess mortality. WIDER IMPLICATIONS OF THE FINDINGS: Our findings justify
      screening for type 2 diabetes mellitus among the mothers with a daughter
      suffering from PCOS to ensure that timely preventive and therapeutic measures
      according to the appropriate guidelines can be taken. STUDY FUNDING/COMPETING
      INTERESTS: No particular funding was received for this study. Y.V.L., M.E.R.-S.,
      N.K., J.R.v.L., M.v.d.B., H.J.G.B. and E.J.G.S. do not have any conflict of
      interest. J.S.E.L. has received fees and grant support from the following
      companies (in alphabetic order): Ferring, Genovum, Merck-Serono, Organon,
      Schering Plough and Serono. B.C.J.M.F. has received fees and grant support from
      the following companies (in alphabetic order): Andromed, Ardana, Ferring,
      Genovum, Merck Serono, Organon, Pantharei Bioscience, PregLem, Schering, Schering
      Plough, Serono, and Wyeth. These companies had no role in study design, data
      collection and analysis, decision to publish, or preparation of the manuscript.

PMID- 24876176
TI  - [Peripheral arterial disease of the lower limbs at Antananarivo University
      Hospital (Madagascar)].
AB  - OBJECTIVE: To analyze problems in the management of reversible peripheral
      arterial disease (PAD) to assess the local technical feasibility of
      revascularization surgery. PATIENTS AND METHODS: This observational study of
      lower-limb PAD in the vascular surgery department at Antananarivo University
      Hospital covered the 3-year period from January 2009 to January 2012. Cases of
      non-atherosclerotic PAD and those with incomplete records were excluded from this
      study. The characteristics studied were time until specialist management began,
      clinical presentation, diagnostic tools used, surgical treatment, course, and
      prognosis in the medium term. RESULTS: Of the 43 files examined, we selected 29
      cases. The time from initial symptoms until management by specialists ranged from
      90 to 730 days; for most patients it was between 366 and 730 days. More than half
      the patients had stage IV PAD according to the classification of Leriche and
      Fontaine, and the general health status of 31% was impaired. Doppler ultrasound
      was readily accessible, but computerized tomographic angiography was possible for
      only 31% of the patients requiring revascularization. Revascularization surgery
      could be performed for 48.2%, while initial amputation was required for 51.7%.
      Outcomes of revascularization surgery after 12 months included death for 6.9% of
      patients, failure of bypass surgery for 6.9%, and a limb salvage rate of 85.7%.
      CONCLUSION: Despite the lack of technical equipment, conventional surgery can
      still save limbs for patients at the reversible stage.

PMID- 24876178
TI  - Profound Versus Superficial Coping With Mortality Threats: Action Orientation
      Moderates Implicit but Not Explicit Outgroup Prejudice.
AB  - Mortality salience (MS) strengthens cultural values but individuals might differ
      in whether this process operates at a superficial, explicit level only or also at
      a profound, implicit level. Two studies investigated whether explicit and
      implicit attitudes toward Muslims after an MS induction vary as a function of
      threat-related action orientation (AOT), an efficient form of self-regulation of
      emotion and behavior that draws on the activation of the implicit, integrated
      self. In Study 1, there was a main effect of MS on explicit prejudice but only
      participants with high levels of AOT showed reduced implicit prejudice following
      MS. In Study 2, this interaction effect was replicated using an alternative
      implicit measure of prejudice. Defense in response to MS might thus not be a
      uniform phenomenon but might be composed of processes operating on different
      (i.e., profound vs. superficial) levels that vary with types of self-regulation
      such as high versus low AOT.

PMID- 24876177
TI  - [Profile and characteristics of pregnant adolescents in Madagascar].
AB  - Madagascar's population is predominantly young: those under 15 years account for
      45% of the total population, and their number is expected to double again by
      2025. First pregnancies accelerate particularly between the ages of 15 and 19
      years among Malagasy teens. It seemed essential to know the profile of pregnant
      adolescents receiving care at a level-2 maternity hospital in the capital so that
      care and social services can be adapted to meet their specific needs. We found
      that teenagers accounted for 16.04% of the admissions to this maternity ward.
      Although more than half had used contraception at some point (most often
      condoms), most had not planned and did not want this pregnancy. The overall fetal
      loss rate was 9.77%, and the rate of complicated induced abortions 4.23%. Nearly
      three quarters (73.15%) of the teens had regular prenatal care. The preterm
      delivery rate was 3.25%. Promoting reproductive health education and preventing
      teenage pregnancy are urgent public health policy priorities in Madagascar. 

PMID- 24876179
TI  - Sexual and gender-based violence in the European asylum and reception sector: a
      perpetuum mobile?
AB  - BACKGROUND: Refugees, asylum seekers and undocumented migrants are at risk of
      sexual and gender-based violence (SGBV) and subsequent ill-health in Europe; yet,
      European minimum reception standards do not address SGBV. Hence, this paper
      explores the nature of SGBV occurring in this sector and discusses determinants
      for 'Desirable Prevention'. METHODS: Applying community-based participatory
      research, we conducted an SGBV knowledge, attitude and practice survey with
      residents and professionals in eight European countries. We conducted logistic
      regression using mixed models to analyse the data in R. RESULTS: Of the 562
      respondents, 58.3% reported cases of direct (23.3%) or peer (76.6%)
      victimization. Our results indicate that when men were involved, it most likely
      concerned sexual perpetration (adjusted odds ratio [aOR]: 4.09, confidence
      interval [CI]: 1.2; 13.89) and physical victimization (aOR: 2.57, CI: 1.65; 4),
      compared with females, who then rather perpetrated emotional violence (aOR: 1.85,
      CI: 1.08; 3.13) and underwent sexual victimization (aOR: 7.14, CI: 3.33; 16.67).
      Compared with others, asylum seekers appeared more likely to perpetrate physical
      (aOR 7.14, CI: 4; 12.5) and endure socio-economic violence (aOR: 10, CI: 1.37;
      100), whereas professionals rather bore emotional (aOR: 2.01, CI: 0.98; 4.12) and
      perpetrated socio-economic violence (aOR: 25.91, CI: 13.41; 50.07). When group
      perpetration (aOR: 2.13, CI: 1.27; 3.58) or victimization (aOR: 1.84, CI: 1.1;
      3.06) occurred, it most likely concerned socio-economic violence. CONCLUSION:
      Within the European asylum reception sector, residents and professionals of both
      sexes experience SGBV victimization and perpetration. Given the lack of
      prevention policies, our findings call for urgent Desirable Prevention programmes
      addressing determinants socio-ecologically.

PMID- 24876180
TI  - [Severe macrophage activation syndrome following visceral leishmaniasis in a
      child].
AB  - Visceral leishmaniasis (VL) is a parasitic disease that is a public health
      problem in Morocco and is one of the frequent infectious causes of macrophage
      activation syndrome (MAS). The combination of clinical and laboratory criteria,
      even very unspecific, make it possible to diagnose MAS, but a definitive
      diagnosis requires cytological examination. Rapid treatment is essential. The
      outcome was favorable. 

PMID- 24876181
TI  - Rab5a is required for spindle length control and kinetochore-microtubule
      attachment during meiosis in oocytes.
AB  - Rab GTPases are highly conserved components of vesicle trafficking pathways.
      Rab5, as a master regulator of endocytic trafficking, has been shown to function
      in membrane tethering and docking. However, the function of Rab5 in meiosis has
      not been addressed. Here, we report elongated spindles and misaligned
      chromosomes, with kinetochore-microtubule misattachments, on specific depletion
      of Rab5a in mouse oocytes. Moreover, the localization and levels of centromere
      protein F (CENPF), a component of the nuclear matrix, are severely reduced at
      kinetochores in metaphase oocytes following Rab5a knockdown. Consistent with this
      finding, nuclear lamina disassembly in the transition from prophase arrest to
      meiosis I is also impaired in Rab5a-depleted oocytes. Notably, oocyte-specific
      ablation of CENPF phenocopies the meiotic defects resulting from Rab5a knockdown.
      In summary, our data support a model where Rab5a-positive vesicles, likely
      through interaction with nuclear lamina, modulate CENPF localization and levels
      at centromeres, consequently ensuring proper spindle length and kinetochore
      microtubule attachment in meiotic oocytes.

PMID- 24876182
TI  - Pharmacological treatment of neuropsychiatric symptoms in Alzheimer's disease: a
      systematic review and meta-analysis.
AB  - BACKGROUND: A wide variety of pharmacological agents are used in the management
      of neuropsychiatric symptoms, which are common in Alzheimer's disease (AD), but
      results from randomised controlled trials (RCTs) on the efficacy and safety of
      these agents are conflicting. OBJECTIVES: To quantify the efficacy and safety of
      pharmacological treatment on neuropsychiatric symptoms in AD patients. METHODS:
      Systematic review and meta-analysis of RCTs comparing pharmacological agents with
      placebo on Neuropsychiatric Inventory (NPI) and safety outcomes in AD patients
      with neuropsychiatric symptoms. RESULTS: Cholinesterase inhibitors (ChEIs) and
      atypical antipsychotics improved NPI total scores (ChEIs: standardised mean
      difference (SMD) -0.12; 95% CI -0.23 to -0.02; atypical antipsychotics: SMD 
      0.21; 95% CI -0.29 to -0.12), but antidepressants (95% CI -0.35 to 0.37) and
      memantine (95% CI -0.27 to 0.03) did not. However, ChEIs and atypical
      antipsychotics increased risk of dropouts due to adverse events (ChEIs: risk
      ratio (RR) 1.64; 95% CI 1.12 to 2.42; atypical antipsychotics: RR 2.24; 95% CI
      1.53 to 3.26) and on incidence of adverse events (ChEIs: RR 1.08; 95% CI 1.01 to
      1.17; atypical antipsychotics: RR 1.17; 95% CI 1.05 to 1.31). For typical
      antipsychotics, no study was included. CONCLUSIONS: ChEIs and atypical
      antipsychotics could improve neuropsychiatric symptoms in AD patients, but with
      bad safety outcomes.

PMID- 24876183
TI  - Abnormal inflammatory activity returns after natalizumab cessation in multiple
      sclerosis.
AB  - OBJECTIVE: To characterise recurrence of multiple sclerosis (MS) inflammatory
      activity during the year following natalizumab (NTZ) cessation. METHODS: Thirty
      two patients with MS were included in a monocentric cohort study. Data were
      collected prospectively during and after NTZ, with serial clinical and MRI
      evaluations. The first relapse occurring after interrupting NTZ was the primary
      outcome measure. The numbers of gadolinium-enhancing lesions before, during and
      after NTZ treatment, were compared. RESULTS: During the year following NTZ
      cessation, the cumulative probability of relapses was estimated at 52.9% and an
      unusually high MRI inflammation was noticed. It was defined by a number of
      gadolinium-enhancing lesions >5 and exceeding the gadolinium lesions existing
      before NTZ initiation. Rebound of MS activity after NTZ cessation was
      characterised by association of relapses and unusual MRI inflammation. Cumulative
      probability of rebound was estimated at 39% and mostly occurring between 3 months
      and 9months after interrupting NTZ. Risk of rebound appears related with a higher
      annualised relapse rate and a lower Expanded Disability Status Scale score before
      NTZ initiation. Rebound was associated with severe recurring relapses in 9% of
      the patients. CONCLUSIONS: This study identifies rebound after NTZ cessation as
      an association of relapses and high MRI activity.

PMID- 24876184
TI  - The link between hyperoxia, delayed cerebral ischaemia and poor outcome after
      aneurysmal SAH: association or therapeutic endeavour.

PMID- 24876185
TI  - Hospitalisation and comorbidities in Parkinson's disease: a large Australian
      retrospective study.
AB  - OBJECTIVES: Patients with Parkinson's disease (PD) require higher levels of care
      during hospitalisation. Management of comorbidities in these patients aims to
      optimise function while minimising complications. The objective of this study was
      to examine patterns of hospitalisation of patients with PD in NSW with regards to
      sociodemographic factors, comorbidities and aspects of clinical management.
      METHODS: A retrospective study of all patients with idiopathic PD and a control
      group of non-PD patients admitted for acute care to NSW hospitals between 2008
      and 2012. RESULTS: The study group comprised 5637 cases and 8143 controls. The
      mean PD patient age was 75.0 years (+/-10.9). Patients with PD had a
      significantly longer hospital stay (median 7 days, IQR 3-13 vs 1 day, IQR 1-7,
      p<0.001) than control patients. Patients with PD were five times more likely to
      be treated for delirium, three times more likely to experience an adverse drug
      event and syncope, more than twice as likely to require management of
      falls/fractures, dementia, gastrointestinal complications, genitourinary
      infections, reduced mobility and other trauma but half as likely to require
      hospitalisation for chronic airways disease and neoplasia, including melanoma,
      than the control group (all p<0.001). CONCLUSIONS: Patients with PD are more
      likely to suffer serious health problems, including delirium, adverse drug
      reactions, syncope, falls and fractures than controls. These findings highlight
      PD as a multisystem neuropsychiatric disorder in which motor and non-motor
      features contribute to morbidity. Increased awareness of the added risk PD poses
      in acute hospitalised patients can be used to inform strategies to improve
      patient outcomes.

PMID- 24876186
TI  - Pathological findings of anti-Yo cerebellar degeneration with Holmes tremor.

PMID- 24876187
TI  - Neuropsychiatric symptoms of dementia: are pharmacological treatments effective
      and safe?

PMID- 24876188
TI  - Herpes simplex encephalitis in glioma patients: a challenging diagnosis.
AB  - OBJECTIVES: In recent years, herpes simplex encephalitis (HSE) has been reported
      with increasing frequency in settings of immunosuppression, such as acquired
      immunodeficiency, transplantation and cancer. As observed, in immunocompromised
      individuals HSE presents peculiar clinical and paraclinical features, and poorer
      prognosis. METHODS: Here we describe a retrospective series of seven cases of HSE
      in patients with high-grade glioma (HGG), collected among three institutions in a
      5-year period (during this time, a total of 1750 patients with HGG were treated).
      RESULTS: Diagnosis of the condition was particularly challenging due to the
      confounding clinical presentation and the atypical biological findings. As a
      result, antiviral treatment was started with a sharp delay compared with
      immunocompetent hosts. Prognosis was poor, with high short-term mortality and
      severe residual disability in survivors. CONCLUSIONS: The substantial incidence
      of HSE observed in our centres together with the difficulty in diagnosing the
      condition suggest that the incidence of this complication may be highly
      underestimated. The aim of our report is to strengthen the observation of HSE in
      patients with HGG and outline the key elements that may allow its diagnosis.

PMID- 24876190
TI  - Serum angiogenin levels are elevated in ALS, but not Parkinson's disease.

PMID- 24876192
TI  - Mosquitoes actively remove drops deposited by fog and dew.
AB  - We report mosquito behaviors for removing accumulated drops of water which would
      otherwise increase the energy expended during takeoff and free flight. These
      techniques take advantage of the insect's small size and great structural
      strength. To dry their wings before takeoff, mosquitoes employ a flutter stroke,
      at double the wingbeat frequency of normal flight, generating nearly 2500
      gravities of acceleration. Mosquitoes may also remove drops by the respective
      accelerations associated with takeoff and collision with the ground. We correlate
      the accelerations and size of drops ejected using a simple model involving the
      drop's inertial force and surface tension. We note mosquitoes may use similar
      techniques to remove synthetic drops, making our observations applicable for
      understanding the resistance of insects to insecticides. 

PMID- 24876189
TI  - Temporal lobe epilepsy and affective disorders: the role of the subgenual
      anterior cingulate cortex.
AB  - OBJECTIVE: Reduced deactivation within the default mode network (DMN) is common
      in individuals with primary affective disorders relative to healthy volunteers
      (HVs). It is unknown whether similar network abnormalities are present in
      temporal lobe epilepsy (TLE) patients with a history of affective
      psychopathology. METHODS: 17 TLE patients with a lifetime affective diagnosis, 31
      TLE patients with no formal psychiatric history and 30 HVs were included. We used
      a visuo-spatial 'n-back' paradigm to compare working memory (WM) network
      activation between these groups. Post hoc analyses included voxel-based
      morphometry and diffusion tensor imaging. The Beck Depression Inventory-Fast
      Screen and Beck Anxiety Inventory were completed on the day of scanning.
      FINDINGS: Each group activated the fronto-parietal WM networks and deactivated
      the typical DMN in response to increasing task demands. Group comparison revealed
      that TLE patients with lifetime affective morbidity showed significantly greater
      deactivation in subgenual anterior cingulate cortex (sACC) than either the TLE
      only or the HVs (p<0.001). This effect persisted after covarying for current
      psychotropic medication and severity of current depressive/anxiety symptoms (all
      p<0.001). Correlational analysis revealed that this finding was not driven by
      differences in task performance. There were no significant differences in grey
      matter volume or structural connectivity between the TLE groups. CONCLUSIONS: Our
      results provide novel evidence suggesting that affective psychopathology in TLE
      has a neurobiological correlate, and in this context the sACC performs
      differently compared with network activity in primary affective disorders.

PMID- 24876191
TI  - Unilateral magnetic resonance guided focused ultrasound thalamotomy for essential
      tremor: practices and clinicoradiological outcomes.
AB  - BACKGROUND: Several options exist for surgical management of essential tremor
      (ET), including radiofrequency lesioning, deep brain stimulation and gamma knife
      radiosurgery of the ventralis intermedius nucleus of the thalamus. Recently,
      magnetic resonance-guided focused ultrasound (MRgFUS) has been developed as a
      less-invasive surgical tool aimed to precisely generate focal thermal lesions in
      the brain. METHODS: Patients underwent tremor evaluation and neuroimaging study
      at baseline and up to 6 months after MRgFUS. Tremor severity and functional
      impairment were assessed at baseline and then at 1 week, 1 month, 3 months and 6
      months after treatment. Adverse effects were also sought and ascertained by
      directed questions, neuroimaging results and neurological examination. RESULTS:
      The current feasibility study attempted MRgFUS thalamotomy in 11 patients with
      medication-resistant ET. Among them, eight patients completed treatment with
      MRgFUS, whereas three patients could not complete the treatment because of
      insufficient temperature. All patients who completed treatment with MRgFUS showed
      immediate and sustained improvements in tremors lasting for the 6-month follow-up
      period. Skull volume and maximum temperature rise were linearly correlated
      (linear regression, p=0.003). Other than one patient who had mild and delayed
      postoperative balance, no patient developed significant postsurgical
      complications; about half of the patients had bouts of dizziness during the
      MRgFUS. CONCLUSIONS: Our results demonstrate that MRgFUS thalamotomy is a safe,
      effective and less-invasive surgical method for treating medication-refractory
      ET. However, several issues must be resolved before clinical application of
      MRgFUS, including optimal patient selection and management of patients during
      treatment.

PMID- 24876193
TI  - A beginner's guide to nutritional profiling in physiology and ecology.
AB  - The nutritional history of an organism is often difficult to ascertain.
      Nonetheless, this information on past diet can be particularly important when
      explaining the role of nutrition in physiological responses and ecological
      dynamics. One approach to infer the past dietary history of an individual is
      through characterization of its nutritional phenotype, an interrelated set of
      molecular and physiological properties that are sensitive to dietary stress.
      Comparisons of nutritional phenotypes between a study organism and reference
      phenotypes have the potential to provide insight into the type and intensity of
      past dietary constraints. Here, we describe this process of nutritional profiling
      for ecophysiological research in which a suite of molecular and physiological
      responses are cataloged for animals experiencing known types and intensities of
      dietary stress and are quantitatively compared with those of unknown individuals.
      We supplement this delineation of the process of nutritional profiling with a
      first-order analysis of its sensitivity to the number of response variables in
      the reference database, their responsiveness to diet, and the size of reference
      populations. In doing so, we demonstrate the considerable promise this approach
      has to transform future studies of nutrition by its ability to provide more and
      better information on responses to dietary stress in animals and their
      populations. 

PMID- 24876194
TI  - Testing the Hamilton-Zuk hypothesis: past, present, and future.
AB  - Hamilton and Zuk proposed a good-genes model of sexual selection in which genetic
      variation can be maintained when females prefer ornaments that indicate
      resistance to parasites. When trait expression depends on a male's resistance,
      the co-adaptive cycles between host resistance and parasite virulence provide a
      mechanism in which genetic variation for fitness is continually renewed. The
      model made predictions at both the intraspecific and interspecific levels. In the
      three decades since its publication, these predictions have been theoretically
      examined in models of varying complexity, and empirically tested across many
      vertebrate and invertebrate taxa. Despite such prolonged interest, however, it
      has turned out to be extremely difficult to empirically demonstrate the process
      described, in part because we have not been able to test the underlying
      mechanisms that would unequivocally identify how parasites act as mediators of
      sexual selection. Here, we discuss how the use of high-throughput sequencing
      datasets available from modern genomic approaches might improve our ability to
      test this model. We expect that important contributions will come through the
      ability to identify and quantify the suite of parasites likely to influence the
      evolution of hosts' resistance, to confidently reconstruct phylogenies of both
      host and parasite taxa, and, perhaps most exciting, to detect generational cycles
      of heritable variants in populations of hosts and parasites. Integrative
      approaches, building on systems undergoing parasite-mediated selection with
      genomic resources already available, will be particularly useful in moving toward
      robust tests of this hypothesis. We finish by presenting case studies of well
      studied host-parasite relationships that represent promising avenues for future
      research. 

PMID- 24876195
TI  - Biomechanics and control of landing in toads.
AB  - Anything that jumps must land, but unlike during jumping when muscles produce
      energy to accelerate the body into the air, controlled landing requires muscles
      to dissipate energy and decelerate the body. Among anurans, toads (genus Bufo)
      exhibit highly coordinated landing behaviors, using their forelimbs to stabilize
      the body after touch-down as they lower their hindlimbs to the ground. Moreover,
      toads land frequently, as they cover distances by stringing together long series
      of relatively short hops. We have been using toads as a model to understand the
      biomechanics and motor control strategies of coordinated landing. Our results
      show that toads prepare for landing differently depending on how far they hop.
      For example, the forelimbs are extended farther prior to impact after long hops
      than after short ones. Such kinematic alterations are mirrored by predictable
      modulation of the recruitment intensity of forelimb muscles before impact, such
      that longer hops lead to higher levels of pre-landing recruitment of muscles.
      These differences in kinematics and muscular activity help to control the most
      flexed configuration of the elbow that is achieved after impact, which in turn
      constrains the extent to which muscles involved in dissipating energy are
      stretched. Indeed, a combination of in vivo and in vitro experiments has shown
      that the elbow-extending anconeus muscle, which is stretched during landing as
      the elbow flexes, rarely reaches lengths longer than those on the plateau of the
      muscle's length-tension curve (where damage becomes more likely). We have also
      been studying how movements of the hindlimbs after take-off help to stabilize
      animals during landing. In particular, the immediate and rapid flexion of a
      toad's knees after take-off leads to a repositioning of the animal's center of
      mass (COM) that better aligns it with ground-reaction forces (GRFs) at impact and
      reduces torques that would destabilize the animal. Finally, recent work on
      sensory feedback involved in preparation for landing demonstrates that vision is
      not required for coordinated landing. Toads can effectively utilize
      proprioceptive and/or vestibular information during take-off to help inform
      themselves about landing conditions, but may also use other sensory modalities
      after take-off to modulate landing behavior. 

PMID- 24876196
TI  - Change in practice after the Surfactant, Positive Pressure and Oxygenation
      Randomised Trial.
AB  - OBJECTIVE: To test the hypothesis that the proportion of endotracheal intubation
      (ETI) in the delivery room (DR) decreased in Neonatal Research Network (NRN)
      centres after the National Institute of Child Health and Human Development NRN
      Surfactant, Positive Pressure, and Oxygenation Randomised Trial (SUPPORT).
      DESIGN: Retrospective cohort study using the prospective NRN generic database.
      SETTING: Eleven centres that participated in the SUPPORT trial and remained part
      of the NRN. Preterm neonates 24(0/7)-27(6/7) weeks' gestational age enrolled in
      the SUPPORT trial were randomised to: (1) DR continuous positive airway pressure
      or DR ETI with early surfactant administration; and (2) oxygen saturation targets
      of 85-89% or 91-95%. The prior NRN feasibility trial had assessed the feasibility
      of randomisation to continuous positive airway pressure versus ETI. PATIENTS:
      Infants 24(0/7)-27(6/7) weeks' gestational age, excluding infants with syndromes
      or major malformations and those on comfort care only. MAIN OUTCOME MEASURE:
      Proportion of DR ETI. RESULTS: The proportion of DR ETI decreased significantly
      in the group of infants from centres that had not participated in the feasibility
      trial (91% before vs 75% after SUPPORT, adjusted relative risk 0.86, 95% CI 0.83
      0.89, p<0.0001) but not in the group of infants from the other centres, where the
      proportion of ETI was already lower prior to initiation of the SUPPORT trial (61%
      before vs 58% after SUPPORT, adjusted relative risk 0.96, 95% CI 0.89 to 1.05,
      p=0.40). CONCLUSION: This study shows that DR ETI changed after SUPPORT only in
      NRN centres that had not participated in a similar trial. TRIAL REGISTRATION
      NUMBER: NCT00063063 (GDB) and NCT00233324 (SUPPORT).

PMID- 24876199
TI  - Pro: sympathetic renal denervation in hypertension and in chronic kidney disease.

PMID- 24876198
TI  - Con: renal denervation for all resistant hypertensive patients: the Emperor's new
      clothes.

PMID- 24876200
TI  - Moderator's view: renal denervation: the jury is still out and the verdict will
      be more complex than initially envisaged.

PMID- 24876203
TI  - Lactate dehydrogenase as a biomarker for silica exposure-induced toxicity in
      agate workers.
AB  - OBJECTIVES: Agate workers are chronically exposed to silica dust generated from
      agate grinding, which makes them susceptible to silicosis. In the absence of
      diagnosis at an early stage, the workers continue to be exposed to silica dust
      until the development of silicosis. The present study was undertaken to
      investigate total lactate dehydrogenase (LDH) activity in blood samples of silica
      exposed agate workers as a non-invasive way to measure silica-induced toxicity.
      METHODS: Blood samples were collected from agate workers and control subjects.
      Total LDH activity was measured in the blood plasma and blood cells of agate
      workers and non-exposed (control) subjects using sodium pyruvate as a substrate.
      The reduction of pyruvate to L-lactate with the concurrent oxidation of
      nicotinamide adenine dinucleotide (NADH) during the assay was monitored by change
      in absorbance (or optical density (OD)) at 340 nm at the fixed interval of 10
      min. The ratio of LDH activity (blood plasma/blood cells) in the blood samples
      was calculated as a measure to detect cytotoxicity in exposed workers. RESULTS:
      The LDH activity in blood plasma samples of exposed workers was found to increase
      about 25 times, while the activity in the blood cells of silica-exposed agate
      workers was reduced to 10% of control subjects. The ratio of LDH activity (blood
      plasma/cells) was found to be 6.6 in the silica-exposed agate workers, while it
      was 0.02 in control (non-exposed) subjects. CONCLUSIONS: This study proposes that
      total LDH activity and the LDH ratio (plasma/cells), along with occupational
      exposure history, are markers for silica exposure-induced toxicity in agate
      workers.

PMID- 24876197
TI  - The impact of a regional care bundle on maternal breast milk use in preterm
      infants: outcomes of the East of England quality improvement programme.
AB  - OBJECTIVE: To evaluate a quality improvement (QI) programme to increase the use
      of maternal breast milk (MBM) in preterm infants. DESIGN: Interrupted time series
      analysis. SETTING: 17 neonatal units in the East of England (EoE) Perinatal
      Network; 144 in the rest of the UK Neonatal Collaborative (UKNC). PATIENTS:
      Infants born <=32(+6) weeks gestation admitted to neonatal care between 2009 and
      2012. INTERVENTION: A 'care bundle' to promote MBM in the EoE. OUTCOMES:
      Percentage of infants receiving exclusive or any MBM at discharge and care days
      where any MBM was received. METHODS: Data were extracted from the National
      Neonatal Research Database; outcomes were compared preintervention and
      postintervention, and in relation to the rest of the UKNC. RESULTS: Exclusive and
      any MBM use at discharge increased from 26% to 33% and 50% to 57% respectively in
      the EoE, though there was no evidence of a step or trend change following the
      introduction of the care bundle. Exclusive MBM use at discharge improved
      significantly faster in EoE than the rest of the UKNC; 0.22% (95% CI 0.11 to
      0.34) increase per month versus 0.05% (95% CI 0.01 to 0.09, p=0.007 for
      difference). The percentage of infants receiving MBM at discharge and care days
      where any MBM was received was not significantly different between EoE and the
      rest of the UKNC. CONCLUSIONS: This QI programme was associated with some
      improvement in MBM use in preterm infants that would not have been evident
      without the use of routinely recorded national comparator data.

PMID- 24876204
TI  - Prognostic stratification of metastatic gastroenteropancreatic neuroendocrine
      neoplasms by 18F-FDG PET: feasibility of a metabolic grading system.
AB  - The tumor proliferation marker, Ki-67 index, is a well-established prognostic
      marker in gastroenteropancreatic neuroendocrine neoplasms (NENs). Noninvasive
      molecular imaging allows whole-body metabolic characterization of metastatic
      disease. We investigated the prognostic impact of (18)F-FDG PET in inoperable
      multifocal disease. METHODS: Retrospective, dual-center analysis was performed on
      89 patients with histologically confirmed, inoperable metastatic
      gastroenteropancreatic NENs undergoing (18)F-FDG PET/CT within the staging
      routine. Metabolic (PET-based) grading was in accordance with the most prominent
      (18)F-FDG uptake (reference tumor lesion): mG1, tumor-to-liver ratio of maximum
      standardized uptake value <= 1.0; mG2, 1.0-2.3; mG3, >2.3. Other potential
      variables influencing overall survival, including age, tumor origin, performance
      status, tumor burden, plasma chromogranin A (>=600 MUg/L), neuron-specific
      enolase (>=25 MUg/L), and classic grading (Ki-67-based) underwent univariate (log
      rank test) and multivariate analysis (Cox proportional hazards model), with a P
      value of less than 0.05 considered significant. RESULTS: The median follow-up
      period was 38 mo (95% confidence interval [CI], 27-49 mo); median overall
      survival of the 89 patients left for multivariate analysis was 29 mo (95% CI, 21
      37 mo). According to metabolic grading, 9 patients (10.2%) had mG1 tumors, 22
      (25.0%) mG2, and 57 (64.8%) mG3. On multivariate analysis, markedly elevated
      plasma neuron-specific enolase (P = 0.016; hazard ratio, 2.9; 95% CI, 1.2-7.0)
      and high metabolic grade (P = 0.015; hazard ratio, 4.7; 95% CI, 1.2-7.0) were
      independent predictors of survival. CONCLUSION: This study demonstrated the
      feasibility of prognostic 3-grade stratification of metastatic
      gastroenteropancreatic NENs by whole-body molecular imaging using (18)F-FDG PET.

PMID- 24876205
TI  - Perfusion scintigraphy versus 256-slice CT angiography in pregnant patients
      suspected of pulmonary embolism: comparison of radiation risks.
AB  - One aim of the current study was to determine normalized dose data for maternal
      radiosensitive organs and embryo/fetus from 256-slice CT pulmonary angiography
      (CTPA) performed on pregnant patients suspected of having pulmonary embolism. A
      second aim was to provide reliable maternal and fetal doses and associated
      radiation cancer risk estimates from 256-slice CTPA and lung perfusion
      scintigraphy (LPS) for comparison. METHODS: Mathematic anthropomorphic phantoms
      were generated to simulate the average woman at early pregnancy and at the third,
      sixth, and ninth months of gestation. In each phantom, 0-3 additional 1.5-cm
      thick fat tissue layers were added to derive 4 phantoms representing pregnant
      women with different body sizes. Monte Carlo methods were used to simulate low
      dose 256-slice CTPA exposures on each of the 16 generated phantoms. Normalized
      organ and embryo/fetal dose data were derived for exposures at 80, 100, and 120
      kV. Maternal effective dose and embryo/fetal dose from 256-slice CTPA and
      associated lifetime attributable risks of radiation cancer were determined for
      different body sizes and gestational stages and compared with corresponding data
      from LPS. RESULTS: For an average-sized pregnant patient at the first trimester,
      the 256-slice CTPA exposure resulted in a maternal effective dose of 1 mSv and an
      embryo/fetal dose of 0.05 mGy. However, maternal effective dose considerably
      increased with body size, whereas embryo/fetal dose increased with both body size
      and gestational stage. Compared with LPS, low-dose CTPA to an average-sized
      pregnant patient resulted in a 30% higher maternal effective dose but a 3.4-6
      times lower embryo/fetal dose. Nevertheless, LPS was associated with less
      aggregated radiation risk for an average-sized pregnant patient, with the
      difference from CTPA being increased further for larger patients. CONCLUSION:
      Compared with CTPA performed with a modern wide-area CT scanner, LPS remains
      comparatively more dose-efficient.

PMID- 24876206
TI  - Prevalence of adverse events to radiopharmaceuticals from 2007 to 2011.
AB  - We studied the changing patterns of radiopharmaceutical use and the incidence of
      adverse events (AEs) to PET radiopharmaceuticals, non-PET radiopharmaceuticals,
      and adjunctive nonradioactive pharmaceuticals in nuclear medicine from 2007 to
      2011. METHODS: Fifteen academic institutions submitted quarterly reports of
      radiopharmaceutical use and AEs covering 2007-2011. RESULTS: 1,024,177
      radiopharmaceutical administrations were monitored: 207,281 diagnostic PET,
      803,696 diagnostic non-PET, and 13,200 therapeutic. In addition, 112,830
      adjunctive nonradioactive pharmaceutical administrations were monitored. The
      annual use of bone scintigraphy and radiotracer therapies was unchanged. PET
      radiopharmaceutical use increased from 17% to 26% of diagnostic procedures (P <
      0.01). The incidence of radiopharmaceutical AEs was 2.1/10(5) administrations,
      with no hospitalizations or deaths. CONCLUSION: From 2007 to 2011, PET studies
      increased, and therapeutic radiopharmaceutical use and bone scintigraphy were
      unchanged. Over 2 decades, the incidence of AEs has remained stable at 2.1
      2.3/10(5) dosages.

PMID- 24876207
TI  - Evaluation of cobalt-labeled octreotide analogs for molecular imaging and auger
      electron-based radionuclide therapy.
AB  - The somatostatin receptor, which is overexpressed by many neuroendocrine tumors,
      is a well-known target for molecular imaging and peptide receptor radionuclide
      therapy. Recently, (57)Co-labeled DOTATOC, an octreotide analog, was shown to
      have the highest affinity yet found for somatostatin receptor subtype 2. The aim
      of this study was to evaluate the biologic effects of novel cobalt-labeled
      octreotide analogs targeting the somatostatin receptor to identify promising
      candidates for molecular imaging and Auger electron-based radionuclide therapy.
      METHODS: Cobalt-labeled DOTATATE, DOTATOC, and DOTANOC were prepared with (57)Co
      or (58m)Co for SPECT or Auger electron-based therapy, respectively. The cellular
      uptake and intracellular distribution of the radioligands were characterized with
      the pancreatic tumor cell line AR42J in vitro, including assessment of the
      therapeutic effects of (58m)Co-DOTATATE via DNA double-strand break and
      proliferation assays. Comparisons with the therapeutic effects of (111)In- and
      (177)Lu-DOTATATE were also performed. Tumor uptake and normal tissue uptake were
      characterized in a subcutaneous pancreatic tumor mouse model. RESULTS: All 3
      cobalt-conjugated peptides resulted in time-dependent and receptor-specific
      uptake, with a high level (>=88%) of cellular internalization in vitro of the
      total cell-associated radioactivity. The DNA double-strand break yield showed a
      dose-dependent increase with activity, whereas cell survival showed a dose
      dependent decrease. (58m)Co-DOTATATE was significantly more efficient in cell
      killing per cumulated decay than (111)In- and (177)Lu-DOTATATE. The in vivo
      pharmacokinetic studies showed a high level of receptor-specific tumor uptake.
      CONCLUSION: All cobalt-labeled radioligands showed a high level of receptor
      specific uptake both in vitro and in vivo in tumor-bearing mice. Furthermore,
      (58m)Co-DOTATATE showed considerable therapeutic effects in vitro and, thus,
      could be an effective agent for eradicating disseminated tumor cells and
      micrometastases.

PMID- 24876208
TI  - Pontine stroke and bladder dysfunction.
AB  - We report the case of a 54-year-old hypertensive woman who presented with sudden
      onset left hemiparesis with facial asymmetry and inability to pass urine. Her
      bladder was distended and she had to be catheterised. MRI of her brain showed a
      large infarct in the right pontine region. Antiplatelet therapy was instituted
      and the patient showed good recovery and was able to walk with support after a
      fortnight at the time of discharge. She was discharged with a catheter in situ.
      After 6 months, she could walk with the support of a stick, but had increased
      frequency and urgency of micturition along with nocturia. Urodynamic study
      revealed detrusor hyper-reflexia, possibly due to involvement of the pontine
      micturition centre.

PMID- 24876209
TI  - Mistaken identity: normotensive scleroderma renal crisis.
AB  - A patient presented with neuromuscular, respiratory and cardiac symptoms and was
      initially diagnosed with amyotrophic lateral sclerosis (ALS), myocardial
      ischaemia and pneumonia. He developed unexplained progressive kidney failure over
      the ensuing week, and his kidney biopsy showed thrombotic microangiopathy that
      led to the correct diagnosis of normotensive scleroderma renal crisis. His
      clinical presentation and course were consistent with systemic sclerosis and
      normotensive scleroderma renal crisis. He was treated with an ACE inhibitor
      (ACEi) and haemodialysis with significant functional improvement over the next 3
      months to his prior baseline with the exception of kidney failure. This case
      highlights a diagnostic challenge requiring astute history and physical
      examination skills, and the value of a kidney biopsy in providing the final
      diagnosis.

PMID- 24876210
TI  - Bilateral sclerosing orbital pseudotumour in an adult.
AB  - Sclerosing pseudotumour of the orbit is a rare idiopathic chronic inflammatory
      process, which greatly mimics neoplasms both clinically and on imaging studies.
      It is therefore important to differentiate this entity from true neoplasms and to
      rule out any systemic associations. We present a rare case of sclerosing orbital
      pseudotumour in an adult man with no systemic illnesses who presented with
      painless progressive proptosis of both eyes and showed a gradual initial response
      to steroid therapy but relapsed after a 2-year interval. 

PMID- 24876211
TI  - Streptococcus viridians bacteraemia and colonic adenocarcinoma.
AB  - Even though Streptococcus bacteraemia is an infrequent presentation of colonic
      malignancies, there is a well-established link between Streptococcus bovis
      bacteraemia and colonic malignancies. Most of the physicians are well aware of
      this correlation and further workup is pursued in most of the cases. However,
      many physicians may not be aware that other species of Streptococcus viridians,
      other than S. bovis, can be associated with colonic malignancies. In this case
      report, we present a case of Streptococcus viridians (anginosus) bacteraemia as a
      complication of an undiagnosed sigmoid adenocarcinoma. While further evidence is
      needed to warrant a gastrointestinal (GI) workup in a patient with other species
      of Streptococcus viridians bacteraemia, we would like to increase the awareness
      in the physicians' community regarding Streptococcus viridians, other than S.
      bovis bacteraemia. This would be especially relevant for patients who have no GI
      screening, as Streptococcus viridians bacteraemia can be an early sign of colonic
      neoplasm. 

PMID- 24876213
TI  - An unusual presentation of endometriosis.
AB  - A 25-year-old nulliparous woman attended an orthopaedic clinic with a 12-month
      history of right hip pain and was found to have a hard tender mass in her right
      groin. Fine-needle aspiration yielded a diagnosis of endometrial glands. The
      lesion was excised completely and the final diagnosis was round ligament
      endometriosis. The patient was pain free 3 months postsurgery. 

PMID- 24876212
TI  - Cytological diagnosis of chondroblastoma: diagnostic challenge for the
      cytopathologist.
AB  - Chondroblastoma is an uncommon osseous neoplasm that accounts for less than 1% of
      all bone tumours. It characteristically arises in the epiphysis or epimetaphyseal
      region of long bones and has been reported to affect people of all ages with
      slight male predilection. WHO has defined chondroblastoma as 'a benign, cartilage
      producing neoplasm usually arising in the epiphyses of skeletally immature
      patients'. The authors document the cytological features on fine-needle
      aspiration cytology of a chondroblastoma which appeared as a lytic lesion in the
      upper end of the right fibula, an uncommon site, in an 18-year-old male patient.
      X-ray feature combined with fine-needle aspiration cytology favoured the
      diagnosis of chondroblastoma, which was further confirmed by histopathological
      examination. 

PMID- 24876214
TI  - Not your average birth: considering the possibility of denied or concealed
      pregnancy.
AB  - A 23-year-old woman presented to the emergency department (ED) with a 3-day
      history of lower back pain. She had seen her general practitioner 2 days
      previously who prescribed trimethoprim for a confirmed urinary tract infection.
      Routine admission observations showed she was tachycardic, tachypnoeic and
      slightly hypotensive but non-feverish with normal oxygen saturations. Her urine
      sample revealed that she was pregnant but was otherwise negative. The patient
      maintained that she was unaware she was pregnant. She was reviewed by an ED staff
      grade who was suspicious of a ruptured ectopic pregnancy. She was subsequently
      referred to the obstetrics and gynaecology registrar who on examination found she
      had a gravid uterus and vaginal examination revealed that her cervix was 8 cm
      dilated. The patient was very promptly admitted onto the labour ward for further
      assessment. She gave birth to a live male infant in the early hours of the next
      morning. 

PMID- 24876215
TI  - Preterm delivery and neonatal meningitis due to transplacental acquisition of non
      typhoidal Salmonella serovar montevideo.
AB  - A male infant was born at 34 weeks' gestation to a primigravida mother. The
      mother had a history of 1 day of diarrhoea and mild fever 8 days prior to
      delivery. Her blood culture was negative during the illness and her stool did not
      grow any pathological organism. The baby had poor feeding during the first day of
      his life followed by hypoglycaemia and episodes of seizure on day 2 and 3 of
      life. Blood culture of the baby and placental swab from the mother grew
      Salmonella serovar montevideo. Both baby and mother were treated with a course of
      cephalosporin for 21 and 7 days, respectively. Although non-typhoidal Salmonella
      often causes gastroenteritis in normal humans, it can cause invasive diseases in
      immunocompromised hosts and people at extremes of ages. Transplacental spread of
      Salmonella needs consideration in favourable epidemiological scenarios as its
      implications on fetal and newborn's life are serious. 

PMID- 24876216
TI  - Triple cardiac rupture.
AB  - Left ventricular free wall rupture and acute ischaemic mitral regurgitation are
      nowadays rare, but still potentially lethal mechanical complications after acute
      myocardial infarction. We report a case of a sequential left ventricular free
      wall rupture, anterolateral papillary muscle disruption, secondary severe mitral
      regurgitation and subsequent posteromedial papillary muscle head rupture in a
      single patient during the same ischaemic episode after myocardial infarction, and
      their related successful surgical procedures and management until discharge.
      Prompt bedside diagnosis and emergent consecutive surgical procedures, as well as
      temporary left ventricular assistance, were crucial in the survival of this
      patient. 

PMID- 24876217
TI  - Effect of the P2Y12 antagonist ticagrelor on neointimal hyperplasia in a rabbit
      carotid anastomosis model?.
AB  - OBJECTIVES: In the present study, we aimed to deterimine the dose-related effects
      of ticagrelor, the first reversible inhibitor of the P2Y12 receptor, found in
      smooth muscle cells as well as platelets, during neointimal hyperplasia in a
      rabbit carotid anastomosis model. METHODS: This study was an experimental,
      prospective, randomized controlled study including 20 New Zealand white female
      rabbits (6-months old; weighing 2300 +/- 300 g). Under general anaesthesia, the
      rabbits underwent transection of the right carotid artery and subsequent
      anastomosis of both ends. The study animals were divided into the following 4
      groups: T1 (ticagrelor 5 mg/kg, orally, daily), T2 (ticagrelor 10 mg/kg, orally,
      daily), T3 (ticagrelor 20 mg/kg, orally, daily) and control (no ticagrelor
      treatment). The single oral doses were administered in phosphate-buffered saline.
      The control group received sterile phosphate-buffered saline (2 ml/kg/day,
      orally) for 3 weeks postoperatively. At the end of the study, the animals were
      killed, and the anastomosed segment of the right carotid artery and part of the
      left carotid artery were excised from each animal. Antibodies against
      transforming growth factor-beta were used in staining of arterial sections, which
      was followed by histomorphological and immunohistochemical studies. RESULTS: The
      median intimal thickness (2.0 +/- 0.14 um left vs 73.4 +/- 35.8 um anastomosed
      right arteries; P <0.05), the median medial thickness (70.8 +/- 5.6 um left vs
      92.3 +/- 4.5 um anastomosed right arteries; P <0.05) and the index ratio of
      intimal thickness to medial thickness (0.03 +/- 0.00 left vs 0.8 +/- 0.35
      anastomosed control right arteries; P <0.05) increased significantly in the
      anastomosed right arteries compared with the left carotid arteries in the control
      group. In the treatment groups, the intimal thickness (73.4 +/- 35.8 um in
      control group vs T1 32.7 +/- 19;1 um, T2 1.9 +/- 0.09 um and T3 2.2 +/- 0.5 um; P
      = 0.047, P = 0.009 and P = 0.009, respectively), carotid artery intima/media
      ratio (0.8 +/- 0.35 in control group vs T1 0.4 +/- 0.2, T2 0.03 +/- 0.01 and T3
      0.03 +/- 0.01 in ticagrelor groups; P = 0.028, P = 0.009 and P = 0.009,
      respectively) and medial thickness (92.3 +/- 4.5 um in control group vs T2 65.6
      +/- 7.1 and T3 66.1 +/- 7.6 um; P = 0.009 and P = 0.009, respectively) decreased
      significantly in the anastomosed right arteries. CONCLUSIONS: This study
      indicates that effective doses (10 and 20 mg/kg, daily) of the antiplatelet agent
      ticagrelor in a rabbit model may be beneficial in prevention of intimal
      hyperplasia. Restenosis due to intimal hyperplasia has been high. Ticagrelor has
      also been linked to inhibition of smooth muscle cell proliferation and, hence,
      reduced intimal hyperplasia.

PMID- 24876218
TI  - Delayed fracture of MatrixRIB precontoured plate system.
AB  - OBJECTIVES: Use of titanium prostheses for reconstructing chest wall defects
      following major chest wall resections is rapidly increasing in popularity.
      Previously, complications including prosthesis fracture have been reported for
      the system secured to the rib ends using clips following chest wall
      reconstruction and pectus excavatum repair. By contrast, fracture failure in
      titanium systems fastening the plate to the rib with locking screws through
      predrilled holes has not been previously reported, possibly owing to differences
      in the design and material of the system. METHODS: We report an index case of
      plate fracture in the latter design following rib reconstruction and discuss the
      pathophysiology and relative risks behind such fractures. RESULTS: Fracture of
      titanium plate occurred after chest impact during sport at 25 months following
      initial plate implantation. Surgical excision was performed because of persistent
      pain and cough. CONCLUSIONS: Fracture failure can occur in those systems
      fastening the plate to the rib with locking-screws, and patients, particularly
      those engaged in contact sports or occupations with chest impact risks, should be
      informed of this possibility during consent, as surgical removal is most likely
      required following implant fracture failur.

PMID- 24876219
TI  - What type of valve is most appropriate for osteogenesis imperfecta patients?
AB  - A best evidence topic in cardiac surgery was written according to a structured
      protocol. The question addressed was in osteogenesis imperfecta (OI) patients
      with valve disease undergoing valve replacement which type of valve
      (bioprosthetic or mechanical) is most appropriate in terms of safety,
      complications and survival. Altogether more than 77 papers were found as a result
      of the reported search, of which 43 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. Previous review articles have presented case reports up to 2009. As
      all published data are based on case reports, we conducted a more detailed
      analysis that included the aforementioned series, reports that were missed prior
      to 2009 and all published data from 2009 to October 2013. Our analysis identified
      43 OI patients. Mechanical valves were used in the majority of cases (31
      patients), bioprosthetic valves in 10 patients and homografts in 2 patients. We
      conclude that based on the best available evidence, it appears that bioprosthetic
      valves have had better outcomes (mortality rate 10%) and a lower valve-related
      complication rate (0%) compared with mechanical valves (mortality rate 16.1%,
      complication rate 16.1%), even though differences were not statistically
      significant. Although the existing evidence is solely based on case reports of a
      relatively small number, we would suggest the use of bioprosthetic valves in OI
      patients with valve disease, as they appear to be safer according to our
      analysis. Moreover, considering the surgical difficulties related to the
      friability and weakness of the tissues in terms of suture lines and implantation
      of the valve as well as the high risk of perioperative bleeding which can be
      related to tissue friability, capillary fragility and platelet dysfunction
      followed by the risk of major traumatic fractures and a possible risk of aortic
      dissection in the future, the bioprosthetic valves seem to be safer taking into
      account the avoidance of lifelong anticoagulation and its secondary bleeding
      complications. 

PMID- 24876220
TI  - A perilous course following myocardial infarction: ischaemic ventricular septal
      defect in a transplanted heart.
AB  - Coronary artery disease in the donor heart is an established cause of early graft
      failure. However, identification of this before implantation is difficult.
      Cardiogenic shock associated with significant myocardial infarction during the
      early postoperative period is rare. Here, we report a case of a 42-year-old man
      who presented acutely with cardiogenic shock; he was supported by short-term
      extracorporeal support as a bridge to transplantation. Following successful
      orthotopic heart transplantation, he sustained coronary artery atheromatous
      plaque rupture, resulting in acute coronary artery occlusion, and subsequently
      developed an ischaemic ventricular septal defect on the third postoperative day. 

PMID- 24876222
TI  - ER stress signaling requires RHD3, a functionally conserved ER-shaping GTPase.
AB  - Whether structure and function are correlated features of organelles is a
      fundamental question in cell biology. Here, we have assessed the ability of
      Arabidopsis mutants with a defective endoplasmic reticulum (ER) structure to
      invoke the unfolded protein response (UPR), an essential ER signaling pathway.
      Through molecular and genetic approaches, we show that loss of the ER-shaping
      GTPase Root Hair Defective 3 (RHD3) specifically disrupts the UPR by interfering
      with the mRNA splicing function of the master regulator IRE1. These findings
      establish a new role for RHD3 in the ER and support specificity of the effects of
      ER-shaping mutations on ER function. 

PMID- 24876223
TI  - Phosphorylation and ubiquitylation are opposing processes that regulate
      endocytosis of the water channel aquaporin-2.
AB  - The post-translational modifications (PTMs) phosphorylation and ubiquitylation
      regulate plasma membrane protein function. Here, we examine the interplay between
      phosphorylation and ubiquitylation of the membrane protein aquaporin-2 (AQP2) and
      demonstrate that phosphorylation can override the previously suggested dominant
      endocytic signal of K63-linked polyubiquitylation. In polarized epithelial cells,
      although S256 is an important phosphorylation site for AQP2 membrane
      localization, the rate of AQP2 endocytosis was reduced by prolonging
      phosphorylation specifically at S269. Despite their close proximity, AQP2
      phosphorylation at S269 and ubiquitylation at K270 can occur in parallel, with
      increased S269 phosphorylation and decreased AQP2 endocytosis occurring when K270
      polyubiquitylation levels are maximal. In vivo studies support this data, with
      maximal levels of AQP2 ubiquitylation occurring in parallel to maximal S269
      phosphorylation and enhanced AQP2 plasma membrane localization. In conclusion, we
      demonstrate for the first time that although K63-linked polyubiquitylation marks
      AQP2 for endocytosis, site-specific phosphorylation can counteract
      polyubiquitylation to determine its final localization. Similar mechanisms might
      exist for other plasma membrane proteins. 

PMID- 24876224
TI  - Lipid droplet formation in response to oleic acid in Huh-7 cells is mediated by
      the fatty acid receptor FFAR4.
AB  - It is unclear how changes in lipid droplet size and number are regulated - for
      example, it is not known whether this involves a signalling pathway or is
      directed by cellular lipid uptake. Here, we show that oleic acid stimulates lipid
      droplet formation by activating the long-chain fatty acid receptor FFAR4, which
      signals through a pertussis-toxin-sensitive G-protein signalling pathway
      involving phosphoinositide 3-kinase (PI3-kinase), AKT (also known as protein
      kinase B) and phospholipase D (PLD) activities. This initial lipid droplet
      formation is not dependent upon exogenous lipid, whereas the subsequent more
      sustained increase in the number of lipid droplets is dependent upon lipid
      uptake. These two mechanisms of lipid droplet formation point to distinct
      potential intervention points.

PMID- 24876227
TI  - Evolution, Practice, and Challenges of Cardiopulmonary Bypass.

PMID- 24876225
TI  - The BAG-1 isoform BAG-1M regulates keratin-associated Hsp70 chaperoning of aPKC
      in intestinal cells during activation of inflammatory signaling.
AB  - Atypical PKC (iota/lambda and zeta; hereafter referred to as aPKC) is a key
      player in the acquisition of epithelial polarity and participates in other
      signaling cascades including the control of NF-kappaB signaling. This kinase is
      post-translationally regulated through Hsp70-mediated refolding. Previous work
      has shown that such a chaperoning activity is specifically localized to keratin
      intermediate filaments. Our work was performed with the goal of identifying the
      molecule(s) that block Hsp70 activity on keratin filaments during inflammation. A
      transcriptional screen allowed us to focus on BAG-1, a multi-functional protein
      that assists Hsp70 in nucleotide exchange but also blocks its activity at higher
      concentrations. We found the BAG-1 isoform BAG-1M upregulated threefold in human
      Caco-2 cells following stimulation with tumor necrosis factor receptor alpha
      (TNFalpha) to induce a pro-inflammatory response, and up to sixfold in mouse
      enterocytes following treatment with dextran sodium sulfate (DSS) to induce
      colitis. BAG-1M, but no other isoform, was found to co-purify with intermediate
      filaments and block Hsp70 activity in the keratin fraction but not in the soluble
      fraction within the range of concentrations found in epithelial cells cultured
      under control and inflammation conditions. Constitutive expression of BAG-1M
      decreased levels of phosphorylated aPKC. By contrast, knockdown of BAG-1, blocked
      the TNFalpha-induced decrease of phosphorylated aPKC. We conclude that BAG-1M
      mediates Hsp70 inhibition downstream of NF-kappaB. 

PMID- 24876228
TI  - Perioperative Maintenance of Tissue Perfusion and Cardiac Output in Cardiac
      Surgery Patients.

PMID- 24876226
TI  - Long-term ultraviolet flux, other potential risk factors, and skin cancer risk: a
      cohort study.
AB  - BACKGROUND: Few prospective studies have examined the relationship between sun
      exposure, other potential risk factors, and risk of different skin cancers
      [including basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and
      melanoma] simultaneously. METHODS: We evaluated the association between a number
      of potential risk factors and skin cancer risk in a cohort of 108,916 US women,
      the Nurses' Health Study II (1989-2009). RESULTS: During 2.05 million years of
      follow-up, we identified 6,955, 880, and 779 diagnoses of BCC, SCC, and melanoma,
      respectively. Compared with participants in the lowest quintile of cumulative
      ultraviolet flux in adulthood, participants in the highest quintile had
      multivariable-adjusted relative risks (RR) of 2.35 (Ptrend < 0.0001) for BCC,
      2.53 (Ptrend = 0.009) for SCC, and 0.68 (Ptrend = 0.38) for melanoma. In
      contrast, the RRs were 1.68 (95% CI, 1.55-1.82) for BCC, 1.68 (95% CI, 1.34-2.11)
      for SCC, and 1.80 (95% CI, 1.42-2.28) for melanoma for participants with >=5
      blistering sunburns when compared with participants without sunburn between ages
      15 and 20 years. We found significant interactions between family history of
      melanoma, number of blistering sunburns between ages 15 and 20 years and BCC
      risk, and between sunburn reaction as a child/adolescent and SCC risk (all
      Pinteraction < 0.05). CONCLUSION: In a cohort of U.S. women, we found that sun
      exposures in both early life and adulthood were predictive of BCC and SCC risks,
      whereas melanoma risk was predominantly associated with sun exposure in early
      life. IMPACT: Our results may have potential implications for the prevention of
      skin cancers. Cancer Epidemiol Biomarkers Prev; 23(6); 1080-9. (c)2014 AACR.

PMID- 24876229
TI  - Aortic Surgery and Deep-Hypothermic Circulatory Arrest: Anesthetic Update.
AB  - Aortic arch surgery has become increasingly complex, and novel surgical
      approaches have been utilized. Efforts aimed at improving neurological outcomes
      in this patient population have been numerous, with varying degrees of success.
      This article summarizes the anesthetic considerations for procedures on the
      aortic arch, including evidence-based outcomes with respect to temperature
      management, perfusion strategies, hemodynamic goals, adjunct agents, and
      neuromonitoring. 

PMID- 24876230
TI  - Recent Advances in Pediatric Cardiopulmonary Bypass.
AB  - There have been numerous recent advances geared specifically toward the practice
      of pediatric cardiopulmonary bypass (CPB). These advances include the development
      of the first oxygenator intended solely for the neonatal CPB patient; pediatric
      oxygenators with low prime volumes and surface areas, which allow flows up to 2
      L/min; pediatric oxygenators with integrated arterial filters; and miniature
      ultrafiltration (UF) devices, which allow for high rates of ultrafiltrate
      removal. When used in combination with heart lung machines with mast-mounted
      pumps, these advances can result in significant decreases in CPB circuit surface
      areas and prime volumes. This may attenuate CPB-associated hemodilution and
      decrease or eliminate the need for homologous red blood cells during or after
      CPB. In addition to these equipment-related advances, changes in myocardial
      protection strategies and the technique of modified UF as it relates to these
      advances are discussed. 

PMID- 24876231
TI  - Pathophysiology of Cardiopulmonary Bypass: Current Strategies for the Prevention
      and Treatment of Anemia, Coagulopathy, and Organ Dysfunction.
AB  - The techniques and equipment of cardiopulmonary bypass (CPB) have evolved over
      the past 60 years, and numerous numbers of cardiac surgical procedures are
      conducted around the world using CPB. Despite more widespread applications of
      percutaneous coronary and valvular interventions, the need for cardiac surgery
      using CPB remains the standard approach for certain cardiac pathologies because
      some patients are ineligible for percutaneous procedures, or such procedures are
      unsuccessful in some. The ageing patient population for cardiac surgery poses a
      number of clinical challenges, including anemia, decreased cardiopulmonary
      reserve, chronic antithrombotic therapy, neurocognitive dysfunction, and renal
      insufficiency. The use of CPB is associated with inductions of systemic
      inflammatory responses involving both cellular and humoral interactions.
      Inflammatory pathways are complex and redundant, and thus, the reactions can be
      profoundly amplified to produce a multiorgan dysfunction that can manifest as
      capillary leak syndrome, coagulopathy, respiratory failure, myocardial
      dysfunction, renal insufficiency, and neurocognitive decline. In this review,
      pathophysiological aspects of CPB are considered from a practical point of view,
      and preventive strategies for hemodilutional anemia, coagulopathy, inflammation,
      metabolic derangement, and neurocognitive and renal dysfunction are discussed. 

PMID- 24876232
TI  - A 2014 Update on Coagulation Management for Cardiopulmonary Bypass.
AB  - Coagulopathy after cardiac surgery with cardiopulmonary bypass is a serious
      complication that may result in massive bleeding requiring transfusion of
      significant amounts of blood products, plasma, and platelets. In addition to
      increased patient morbidity and mortality it is associated with longer hospital
      stay and increased resource utilization. The current review discusses aspects in
      cardiopulmonary bypass-induced coagulopathy with emphasis on point-of-care
      testing and individualized "goal-directed" therapy in patients who develop
      excessive bleeding after cardiac surgery. 

PMID- 24876235
TI  - AZD9272 and AZD2066: selective and highly central nervous system penetrant mGluR5
      antagonists characterized by their discriminative effects.
AB  - The metabotropic glutamate receptor 5 (mGluR5) antagonists fenobam, MPEP (2
      methyl-6-(phenylethynyl)pyridine), and MTEP (3-[(2-methyl-1,3-thiazol-4
      yl)ethynyl]pyridine) were previously shown to not cause N-methyl-D-aspartate
      antagonist-like psychoactive effects in phencyclidine (PCP) drug discrimination
      studies, but to cause MTEP-like discrimination in rats, suggesting that the
      psychoactive and psychotomimetic effects reported with fenobam in humans were
      likely mediated by mGluR5 antagonist mechanisms. The present study was designed
      to characterize AZD9272 (3-fluoro-5-(3-(5-fluoropyridin-2-yl)-1,2,4-oxadiazol5
      yl)benzonitrile) and AZD2066 [4-(5-{(1R)-1-[5-(3-chlorophenyl)isoxazol-3
      yl]ethoxy}-4-methyl-4H-1,2,4-triazol-3-yl)pyridine], two mGluR5 antagonists taken
      to clinical development for analgesia. AZD9272 was evaluated in several groups of
      rats trained to discriminate cocaine, PCP, chlordiazepoxide, (-)-Delta(9)
      tetrahydrocannabinol [(-)-Delta(9)-THC], or MTEP from no drug. AZD9272 shared
      discriminative properties with MTEP only. The discriminative half-life was 3.23
      hours for MTEP and 21.93 hours for AZD9272 in rats trained to discriminate MTEP
      from no drug. Other rats were successfully trained to discriminate AZD9272 from
      no drug. Due to the long duration of action of AZD9272, discrimination training
      was conducted every other day. AZD9272 caused a dose-dependent increase in
      AZD9272-appropriate responding. PCP did not cause AZD9272-appropriate responding,
      whereas MTEP, fenobam, and the mGluR5 antagonist AZD2066 did. The discriminative
      half-life of AZD9272 was 24.3 hours in rats trained to discriminate AZD9272 from
      no drug. It is concluded that the discriminative effects of AZD9272 and AZD2066
      are similar to those of previously investigated mGluR5 antagonists and dissimilar
      to those of cocaine, PCP, chlordiazepoxide, and (-)-Delta(9)-THC. The
      discriminative half-life of AZD9272 is approximately 7-fold longer than for MTEP.
      These data support and extend previous findings suggesting that mGluR5 antagonism
      causes psychoactive effects selectively mediated by mGluR5 mechanisms. 

PMID- 24876236
TI  - Health of Danish seafarers and fishermen 1970-2010: What have register-based
      studies found?
AB  - BACKGROUND: This study aimed to review Danish register-studies on seafarers' and
      fishermen's health and safety. METHODS: Register-based or register-linked studies
      from 1970 until 2012 were identified and reviewed. Four categories of studies
      were included: mortality, hospitalization, specific diagnoses and conditions and
      accidents. Standardized risks estimates were typically calculated by comparison
      with the total Danish working population. RESULTS: Elevated rates were found in
      all four categories. For mortality male seafarers had excess rates of accidents,
      cirrhosis of the liver, cancer, and suicides, and fishermen of accidents and
      cardiovascular disorders. Female seafarers in male-dominated occupations also had
      increased mortality rates. Elevated hospitalization rates for male seafarers were
      particularly prominent for endocrine/nutritional conditions, cervical discopathy,
      gastrointestinal and cardiovascular diseases, cancers, hearing impairment, and
      injuries, and for female seafarers cancers, circulatory and genitourinary
      diseases and injuries. Fishermen had increased hospitalization rates for
      cardiovascular diseases, bronchitis, emphysema, lung cancer, gonarthrosis,
      thoracolumbar discopathy, rotator cuff syndrome, carpal tunnel syndrome, injuries
      and hearing impairment. Specific diagnoses and conditions: There was an elevated
      risk of tuberculosis, hepatitis B and certain cancers for male seafarers, and of
      obesity and occupational accidents for both fishermen and seafarers. CONCLUSIONS:
      In spite of safety measures and significant structural changes in the Danish
      merchant and fishing fleet, the spectrum of health indicators continues to
      indicate considerable risk factors in the maritime environment and/or the
      lifestyle of seafarers and fishermen. Future monitoring of fishermen's and
      seafarers' health will remain essential for implementing appropriate preventive
      measures.

PMID- 24876234
TI  - Further characterization of quinpirole-elicited yawning as a model of dopamine D3
      receptor activation in male and female monkeys.
AB  - The dopamine (DA) D3 receptor (D3R) has been associated with impulsivity,
      pathologic gambling, and drug addiction, making it a potential target for
      pharmacotherapy development. Positron emission tomography studies using the D3R
      preferring radioligand [(11)C]PHNO ([(11)C](+)-propyl-hexahydro-naphtho-oxazin)
      have shown higher binding potentials in drug abusers compared with control
      subjects. Preclinical studies have examined D3R receptor activation using the DA
      agonist quinpirole and the unconditioned behavior of yawning. However, the
      relationship between quinpirole-elicited yawning and D3R receptor availability
      has not been determined. In Experiment 1, eight drug-naive male rhesus monkeys
      were scanned with [(11)C]PHNO, and the ability of quinpirole (0.01-0.3 mg/kg
      i.m.) to elicit yawning was examined. Significant positive (globus pallidus) and
      negative (caudate nucleus, putamen, ventral pallidum, and hippocampus)
      relationships between D3R receptor availability and quinpirole-induced yawns were
      noted. Experiment 2 replicated earlier findings that a history of cocaine self
      administration (n = 11) did not affect quinpirole-induced yawning and extended
      this to examine monkeys (n = 3) with a history of methamphetamine (MA) self
      administration and found that monkeys with experience self-administering MA
      showed greater potency and significantly higher quinpirole-elicited yawning
      compared with controls. Finally, quinpirole-elicited yawning was studied in drug
      naive female monkeys (n = 6) and compared with drug-naive male monkeys (n = 8).
      Sex differences were noted, with quinpirole being more potent and eliciting
      significantly more yawns in males compared with females. Taken together these
      findings support the use of quinpirole-elicited yawning as a behavioral tool for
      examining D3R activation in monkeys and that both drug history and sex may
      influence individual sensitivity to the behavioral effects of D3R compounds. 

PMID- 24876237
TI  - Flavihumibacter solisilvae sp. nov., isolated from forest soil.
AB  - A Gram-stain-positive, strictly aerobic, yellow colony-forming bacterium,
      designated strain 3-3(T), was isolated from forest soil of Bac Kan Province in
      Vietnam. Cells were non-motile rods without gliding motility, showing oxidase-
      and catalase-positive reactions. Growth was observed at 20-37  degrees C
      (optimum, 28  degrees C) and pH 5.5-9.5 (optimum, pH 7.5). The major cellular
      fatty acids were iso-C(15 : 0), iso-C(15 : 1) G and summed feature 3 (comprising
      C(16 : 1)omega6c and/or C(16 : 1)omega7c). Strain 3-3(T) contained
      phosphatidylethanoamine, three unidentified aminolipids and three unidentified
      lipids. The G+C content of the genomic DNA was 49.5 mol% and the only isoprenoid
      quinone detected was menaquinone 7 (MK-7). Phylogenetic analysis based on 16S
      rRNA gene sequences indicated that strain 3-3(T) formed a tight phylogenetic
      lineage with Flavihumibacter petaseus T41(T) with a bootstrap value of 100%.
      Strain 3-3(T) was related most closely to F. petaseus T41(T) with 97.3% 16S rRNA
      gene sequence similarity and the level of DNA-DNA relatedness between the two was
      9.4+/-1.2%. Based on phenotypic, chemotaxonomic and molecular features, strain 3
      3(T) represents a novel species of the genus Flavihumibacter, for which the name
      Flavihumibacter solisilvae sp. nov. is proposed. The type strain is 3-3(T) ( =
      KACC 17917(T) = JCM 19891(T)).

PMID- 24876238
TI  - Tamlana sedimentorum sp. nov., isolated from shallow sand sediments of the Sea of
      Japan.
AB  - An aerobic, Gram-stain-negative, saffron-pigmented, non-motile bacterial strain
      KMM 9545(T), was isolated from a marine sand sediment sample obtained from the
      Sea of Japan seashore and characterized in a taxonomic study using a polyphasic
      approach. The 16S rRNA gene sequence of strain KMM 9545(T) showed a high level of
      similarity to species of the genus Gaetbulibacter (95.1-96.2%), the type strains
      of species of the genus Tamlana (94.9-96.1%) and members of the genus Algibacter
      (94.8-96.1%). Phylogenetic analysis based on the 16S rRNA gene sequences
      positioned strain KMM 9545(T) as a distinct lineage in the cluster comprising
      species of the genus Tamlana. Strain KMM 9545(T) grew at temperatures between 5
      36  degrees C and in the presence of 2-4% (w/v) NaCl. It contained MK-6 as the
      predominant menaquinone and iso-C(15 : 0), iso-C(15 : 1), iso-C(17 : 1) 3-OH, iso
      C(15 : 0) 3-OH and iso-C(15 : 0) 2-OH as the major fatty acids. The genomic DNA
      G+C content was 31.3 mol%. On the basis of the phenotypic characteristics and
      phylogenetic distance, it can be concluded that strain KMM 9545(T) represents a
      novel species of the genus Tamlana, for which the name Tamlana sedimentorum sp.
      nov. is proposed. The type strain is KMM 9545(T) ( = NRIC 0921(T) = JCM
      19808(T)).

PMID- 24876239
TI  - Campylobacter corcagiensis sp. nov., isolated from faeces of captive lion-tailed
      macaques (Macaca silenus).
AB  - An investigation of the prevalence of Campylobacter ureolyticus in a variety of
      animals led to the identification of the strain CIT 045(T), in the faeces of
      captive lion-tailed macaques (Macaca silenus). Originally, believed to be
      Campylobacter ureolyticus based on the colony morphology and positive urease
      test, analysis of 16S rRNA and hsp60 gene sequences of this isolate revealed that
      the strain differs significantly from other species of the genus Campylobacter
      described to date. Species-specific primers for 16S rRNA and hsp60 genes were
      designed and used to identify two additional strains isolated from faeces samples
      from other macaques. Nucleotide sequence analysis of the 16S rRNA and hsp60 genes
      revealed <=95% and <=82  % sequence similarity to recognized species of the genus
      Campylobacter respectively. All three isolates formed a distinct group within the
      genus Campylobacter based on their 16S rRNA and hsp60 sequences and matrix
      assisted laser desorption/ionization time of flight (MALDI-TOF) profiles. The
      unique species status was further supported by phenotypic characteristics of the
      isolates. All isolates were found to be oxidase-, catalase- and urease-positive,
      they grew well at 37  degrees C and 42  degrees C and produced H2S on TSI (triple
      sugar iron) and SIM (sulfide indole motility) media. The name Campylobacter
      corcagiensis sp. nov. is proposed for this novel species, with the strain CIT
      045(T) as the type strain CIT 045(T) ( = LMG 27932(T), CCUG 64942(T)).

PMID- 24876240
TI  - Lactobacillus furfuricola sp. nov., isolated from Nukadoko, rice bran paste for
      Japanese pickles.
AB  - Two strains of lactic acid bacteria, Nu27(T) and Nu29, were isolated from
      Nukadoko, rice bran paste for Japanese pickles. The isolates were Gram-stain
      positive, rod-shaped, catalase-negative, non-motile and facultatively anaerobic
      lactic acid bacteria. The isolates showed identical 16S rRNA gene sequences. The
      closest relatives to strain Nu27(T) based on 16S rRNA gene sequence similarities
      were Lactobacillus versmoldensis KU-3(T) (98.9% 16S rRNA gene sequence
      similarity), Lactobacillus nodensis iz4b(T) (96.3%) and Lactobacillus tucceti
      CECT 5290(T) (97.2%). DNA-DNA relatedness values revealed genotype separation of
      the two isolates from the above three species. Based on the physiological,
      biochemical and genotypic characteristics provided, the isolates represent a
      novel species of the genus Lactobacillus, for which name is Lactobacillus
      furfuricola proposed. The type strain is Nu 27(T) ( = JCM 18764(T) = NRIC 0900(T)
      = DSM 27174(T)).

PMID- 24876241
TI  - Desulfocarbo indianensis gen. nov., sp. nov., a benzoate-oxidizing, sulfate
      reducing bacterium isolated from water extracted from a coal bed.
AB  - A novel, strictly anaerobic, sulfate-reducing bacterium, designated strain
      SCBM(T), was isolated from water extracted from a coal bed in Indiana, USA. The
      isolate was characterized by a polyphasic taxonomic approach that included
      phenotypic and genotypic characterizations. Cells of strain SCBM(T) were vibrio
      shaped, polarly flagellated, Gram-negative, motile, oxidase-negative and weakly
      catalase-positive. Growth of strain SCBM(T) was observed at NaCl concentrations
      ranging from 0 to 300 mM. However, no growth was observed when 1 M or more NaCl
      was present. Growth was observed at 16-37  degrees C, with optimal growth at 30 
      degrees C. The optimum pH for growth was 7, although growth was observed from pH
      6.5 to 8. The doubling time under optimal growth conditions (30  degrees C, pH 7,
      2.5 mM benzoate, 14 mM sulfate) was 2.7 days. Bicarbonate, HEPES, PIPES and MES
      were effective buffers for growth of strain SCBM(T), but citrate inhibited
      growth. When sulfate was provided as the electron acceptor, strain SCBM(T) grew
      autotrophically with hydrogen as the electron donor and heterotrophically on
      benzoate, formate, acetate, pyruvate, butyrate, fumarate, succinate and
      palmitate. None of the substrates tested supported fermentative growth.
      Thiosulfate and sulfate were used as electron acceptors coupled to benzoate
      oxidation, but sulfite, elemental sulfur, DMSO, anthraquinone 2,6-disulfonate,
      nitrate, nitrite, ferric citrate, hydrous iron oxide and oxygen were not. The G+C
      content of genomic DNA was 62.5 mol%. The major cellular fatty acids were anteiso
      C(15 : 0) and C(18 : 1)omega7c. Phylogenetic analysis based on 16S rRNA gene
      sequencing placed strain SCBM(T) into a distinct lineage within the class
      Deltaproteobacteria. The closest, cultivated phylogenetic relative of strain
      SCBM(T) was Desulfarculus baarsii DSM 2075(T), with only 91.7% 16S rRNA gene
      sequence identity. On the basis of phenotypic and genotypic analyses, strain
      SCBM(T) represents a novel genus and species of sulfate-reducing bacteria, for
      which the name Desulfocarbo indianensis gen. nov., sp. nov. is proposed. The type
      strain of Desulfocarbo indianensis is SCBM(T) ( = DSM 28127(T) = JCM 19826(T)).
      Desulfocarbo is the second genus of the order Desulfarculales.

PMID- 24876242
TI  - Acute carotid T occlusion in a young patient: cryptogenic origin?

PMID- 24876243
TI  - Methodology for a community-based stroke preparedness intervention: the Acute
      Stroke Program of Interventions Addressing Racial and Ethnic Disparities Study.
AB  - BACKGROUND AND PURPOSE: Acute stroke education has focused on stroke symptom
      recognition. Lack of education about stroke preparedness and appropriate actions
      may prevent people from seeking immediate care. Few interventions have rigorously
      evaluated preparedness strategies in multiethnic community settings. METHODS: The
      Acute Stroke Program of Interventions Addressing Racial and Ethnic Disparities
      (ASPIRE) project is a multilevel program using a community-engaged approach to
      stroke preparedness targeted to underserved black communities in the District of
      Columbia. This intervention aimed to decrease acute stroke presentation times and
      increase intravenous tissue-type plasminogen activator utilization for acute
      ischemic stroke. RESULTS: Phase 1 included (1) enhancement of focus of emergency
      medical services on acute stroke; (2) hospital collaborations to implement and
      enrich acute stroke protocols and transition District of Columbia hospitals
      toward primary stroke center certification; and (3) preintervention acute stroke
      patient data collection in all 7 acute care District of Columbia hospitals. A
      community advisory committee, focus groups, and surveys identified perceptions of
      barriers to emergency stroke care. Phase 2 included a pilot intervention and
      subsequent citywide intervention rollout. A total of 531 community interventions
      were conducted, reaching >10,256 participants; 3289 intervention evaluations were
      performed, and 19,000 preparedness bracelets and 14,000 stroke warning magnets
      were distributed. Phase 3 included an evaluation of emergency medical services
      and hospital processes for acute stroke care and a year-long postintervention
      acute stroke data collection period to assess changes in intravenous tissue-type
      plasminogen utilization. CONCLUSIONS: We report the methods, feasibility, and
      preintervention data collection efforts of the ASPIRE intervention. CLINICAL
      TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier:
      NCT00724555.

PMID- 24876244
TI  - Optimal workflow and process-based performance measures for endovascular therapy
      in acute ischemic stroke: analysis of the Solitaire FR thrombectomy for acute
      revascularization study.
AB  - BACKGROUND AND PURPOSE: We report on workflow and process-based performance
      measures and their effect on clinical outcome in Solitaire FR Thrombectomy for
      Acute Revascularization (STAR), a multicenter, prospective, single-arm study of
      Solitaire FR thrombectomy in large vessel anterior circulation stroke patients.
      METHODS: Two hundred two patients were enrolled across 14 centers in Europe,
      Canada, and Australia. The following time intervals were measured: stroke onset
      to hospital arrival, hospital arrival to baseline imaging, baseline imaging to
      groin puncture, groin puncture to first stent deployment, and first stent
      deployment to reperfusion. Effects of time of day, general anesthesia use, and
      multimodal imaging on workflow were evaluated. Patient characteristics and
      workflow processes associated with prolonged interval times and good clinical
      outcome (90-day modified Rankin score, 0-2) were analyzed. RESULTS: Median times
      were onset of stroke to hospital arrival, 123 minutes (interquartile range, 163
      minutes); hospital arrival to thrombolysis in cerebral infarction (TICI) 2b/3 or
      final digital subtraction angiography, 133 minutes (interquartile range, 99
      minutes); and baseline imaging to groin puncture, 86 minutes (interquartile
      range, 24 minutes). Time from baseline imaging to puncture was prolonged in
      patients receiving intravenous tissue-type plasminogen activator (32-minute mean
      delay) and when magnetic resonance-based imaging at baseline was used (18-minute
      mean delay). Extracranial carotid disease delayed puncture to first stent
      deployment time on average by 25 minutes. For each 1-hour increase in stroke
      onset to final digital subtraction angiography (or TICI 2b/3) time, odds of good
      clinical outcome decreased by 38%. CONCLUSIONS: Interval times in the STAR study
      reflect current intra-arterial therapy for patients with acute ischemic stroke.
      Improving workflow metrics can further improve clinical outcome. CLINICAL TRIAL
      REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01327989.

PMID- 24876246
TI  - Warfarin-associated intracerebral hemorrhage after ischemic stroke.
AB  - BACKGROUND AND PURPOSE: The aim was to investigate the risk of intracerebral
      hemorrhage (ICH) in patients with ischemic stroke taking warfarin and whether
      this risk changed over time. METHODS: Between 2001 and 2008, the Swedish Stroke
      Register registered 12,790 patients with ischemic stroke discharged on warfarin.
      The patients was studied in two 4-year periods (inclusion 2001-2004: follow-up
      until 2005 and inclusion 2005-2008: follow-up until 2009) for which rates of
      subsequent ICH were calculated. Adjusted hazard ratios, comparing the second
      period with the first period, were estimated in Cox regression models. RESULTS:
      Of 6039 patients, 58 patients (1.0%) in the first period and 69 of 6751 patients
      (1.0%) in the second period had subsequent ICH. Annual rates of ICH ranged from
      0.37% in the first period to 0.39% in the second period (adjusted hazard ratio,
      1.04; 95% confidence interval, 0.73-1.48). CONCLUSIONS: In this nationwide study,
      the risk of warfarin-associated ICH among ischemic stroke patients was low and
      did not change during the 2000s.

PMID- 24876245
TI  - Pretreatment blood-brain barrier damage and post-treatment intracranial
      hemorrhage in patients receiving intravenous tissue-type plasminogen activator.
AB  - BACKGROUND AND PURPOSE: Early blood-brain barrier damage after acute ischemic
      stroke has previously been qualitatively linked to subsequent intracranial
      hemorrhage (ICH). In this quantitative study, it was investigated whether the
      amount of blood-brain barrier damage evident on pre-tissue-type plasminogen
      activator MRI scans was related to the degree of post-tissue-type plasminogen
      activator ICH in patients with acute ischemic stroke. METHODS: Analysis was
      performed on a database of patients with acute ischemic stroke provided by the
      Stroke Imaging Repository (STIR) and Virtual International Stroke Trials Archive
      (VISTA) Imaging Investigators. Patients with perfusion-weighted imaging
      lesions>10 mL and negative gradient-recalled echo imaging before intravenous
      tissue-type plasminogen activator were included. Postprocessing of the perfusion
      weighted imaging source images was performed to estimate changes in blood-brain
      barrier permeability within the perfusion deficit relative to the unaffected
      hemisphere. Follow-up gradient-recalled echo images were reviewed for evidence of
      ICH and divided into 3 groups according to European Cooperative Acute Stroke
      Study (ECASS) criteria: no hemorrhage, hemorrhagic infarction, and parenchymal
      hematoma. RESULTS: Seventy-five patients from the database met the inclusion
      criteria, 28 of whom experienced ICH, of which 19 were classified as hemorrhagic
      infarction and 9 were classified as parenchymal hematoma. The mean permeability
      (+/-SDs), expressed as an index of contrast leakage, was 17.0+/-8.8% in the no
      hemorrhage group, 19.4+/-4.0% in the hemorrhagic infarction group, and 24.6+/
      4.5% in the parenchymal hematoma group. Permeability was significantly correlated
      with ICH grade in univariate (P=0.007) and multivariate (P=0.008) linear
      regression modeling. CONCLUSIONS: A perfusion-weighted imaging-derived index of
      blood-brain barrier damage measured before intravenous tissue-type plasminogen
      activator is given is associated with the severity of ICH after treatment in
      patients with acute ischemic stroke.

PMID- 24876251
TI  - Consequences of Whole-Genome Triplication as Revealed by Comparative Genomic
      Analyses of the Wild Radish Raphanus raphanistrum and Three Other Brassicaceae
      Species.
AB  - Polyploidization events are frequent among flowering plants, and the duplicate
      genes produced via such events contribute significantly to plant evolution. We
      sequenced the genome of wild radish (Raphanus raphanistrum), a Brassicaceae
      species that experienced a whole-genome triplication event prior to diverging
      from Brassica rapa. Despite substantial gene gains in these two species compared
      with Arabidopsis thaliana and Arabidopsis lyrata, ~70% of the orthologous groups
      experienced gene losses in R. raphanistrum and B. rapa, with most of the losses
      occurring prior to their divergence. The retained duplicates show substantial
      divergence in sequence and expression. Based on comparison of A. thaliana and R.
      raphanistrum ortholog floral expression levels, retained radish duplicates
      diverged primarily via maintenance of ancestral expression level in one copy and
      reduction of expression level in others. In addition, retained duplicates
      differed significantly from genes that reverted to singleton state in function,
      sequence composition, expression patterns, network connectivity, and rates of
      evolution. Using these properties, we established a statistical learning model
      for predicting whether a duplicate would be retained postpolyploidization.
      Overall, our study provides new insights into the processes of plant duplicate
      loss, retention, and functional divergence and highlights the need for further
      understanding factors controlling duplicate gene fate.

PMID- 24876250
TI  - miR824-Regulated AGAMOUS-LIKE16 Contributes to Flowering Time Repression in
      Arabidopsis.
AB  - The timing of flowering is pivotal for maximizing reproductive success under
      fluctuating environmental conditions. Flowering time is tightly controlled by
      complex genetic networks that integrate endogenous and exogenous cues, such as
      light, temperature, photoperiod, and hormones. Here, we show that AGAMOUS-LIKE16
      (AGL16) and its negative regulator microRNA824 (miR824) control flowering time in
      Arabidopsis thaliana. Knockout of AGL16 effectively accelerates flowering in
      nonvernalized Col-FRI, in which the floral inhibitor FLOWERING LOCUS C (FLC) is
      strongly expressed, but shows no effect if plants are vernalized or grown in
      short days. Alteration of AGL16 expression levels by manipulating miR824
      abundance influences the timing of flowering quantitatively, depending on the
      expression level and number of functional FLC alleles. The effect of AGL16 is
      fully dependent on the presence of FLOWERING LOCUS T (FT). Further experiments
      show that AGL16 can interact directly with SHORT VEGETATIVE PHASE and indirectly
      with FLC, two proteins that form a complex to repress expression of FT. Our data
      reveal that miR824 and AGL16 modulate the extent of flowering time repression in
      a long-day photoperiod.

PMID- 24876252
TI  - An EAR-Dependent Regulatory Module Promotes Male Germ Cell Division and Sperm
      Fertility in Arabidopsis.
AB  - The production of the sperm cells in angiosperms requires coordination of cell
      division and cell differentiation. In Arabidopsis thaliana, the germline-specific
      MYB protein DUO1 integrates these processes, but the regulatory hierarchy in
      which DUO1 functions is unknown. Here, we identify an essential role for two
      germline-specific DUO1 target genes, DAZ1 and DAZ2, which encode EAR motif
      containing C2H2-type zinc finger proteins. We show that DAZ1/DAZ2 are required
      for germ cell division and for the proper accumulation of mitotic cyclins.
      Importantly, DAZ1/DAZ2 are sufficient to promote G2- to M-phase transition and
      germ cell division in the absence of DUO1. DAZ1/DAZ2 are also required for DUO1
      dependent cell differentiation and are essential for gamete fusion at
      fertilization. We demonstrate that the two EAR motifs in DAZ1/DAZ2 mediate their
      function in the male germline and are required for transcriptional repression and
      for physical interaction with the corepressor TOPLESS. Our findings uncover an
      essential module in a regulatory hierarchy that drives mitotic transition in male
      germ cells and implicates gene repression pathways in sperm cell formation and
      fertility.

PMID- 24876253
TI  - Repair of Site-Specific DNA Double-Strand Breaks in Barley Occurs via Diverse
      Pathways Primarily Involving the Sister Chromatid.
AB  - DNA double-strand break (DSB) repair mechanisms differ in their requirements for
      a homologous repair template and in the accuracy of the result. We aimed to
      quantify the outcome of repair of a single targeted DSB in somatic cells of young
      barley (Hordeum vulgare) plants. Amplicon sequencing of three reporter constructs
      revealed 47 to 58% of reads as repaired via nonhomologous end-joining (NHEJ) with
      deletions and/or small (1 to 3 bp) insertions. Alternative NHEJ revealed 2 to 5
      bp microhomology (15.7% of cases) or new replication-mediated short duplications
      at sealed breaks. Although deletions outweigh insertions in barley, this bias was
      less pronounced and deleted sequences were shorter than in Arabidopsis thaliana.
      Between 17 and 33% of reads likely represent restoration of the original
      sequence. Depending on the construct, 20 to 33% of reads arose via gene
      conversion (homologous recombination). Remarkably, <1 to >8% of reads apparently
      display synthesis-dependent strand annealing linked with NHEJ, inserting 4 to 61
      bp, mostly originating from the surrounding of breakpoints. Positional
      coincidence of >81% of sister chromatid exchanges with target loci is
      unprecedented for higher eukaryotes and indicates that most repair events for
      staggered DSBs, at least in barley, involve the sister chromatid and occur during
      S or G2 phase of the cell cycle.

PMID- 24876256
TI  - Uncovering Male Germline Development in Arabidopsis: The Gametophyte Revealed.

PMID- 24876255
TI  - Large-Scale Proteomics of the Cassava Storage Root and Identification of a Target
      Gene to Reduce Postharvest Deterioration.
AB  - Cassava (Manihot esculenta) is the most important root crop in the tropics, but
      rapid postharvest physiological deterioration (PPD) of the root is a major
      constraint to commercial cassava production. We established a reliable method for
      image-based PPD symptom quantification and used label-free quantitative
      proteomics to generate an extensive cassava root and PPD proteome. Over 2600
      unique proteins were identified in the cassava root, and nearly 300 proteins
      showed significant abundance regulation during PPD. We identified protein
      abundance modulation in pathways associated with oxidative stress,
      phenylpropanoid biosynthesis (including scopoletin), the glutathione cycle, fatty
      acid alpha-oxidation, folate transformation, and the sulfate reduction II
      pathway. Increasing protein abundances and enzymatic activities of glutathione
      associated enzymes, including glutathione reductases, glutaredoxins, and
      glutathione S-transferases, indicated a key role for ascorbate/glutathione
      cycles. Based on combined proteomics data, enzymatic activities, and lipid
      peroxidation assays, we identified glutathione peroxidase as a candidate for
      reducing PPD. Transgenic cassava overexpressing a cytosolic glutathione
      peroxidase in storage roots showed delayed PPD and reduced lipid peroxidation as
      well as decreased H2O2 accumulation. Quantitative proteomics data from ethene and
      phenylpropanoid pathways indicate additional gene candidates to further delay
      PPD. Cassava root proteomics data are available at www.pep2pro.ethz.ch for easy
      access and comparison with other proteomics data.

PMID- 24876254
TI  - Bipolar Plasma Membrane Distribution of Phosphoinositides and Their Requirement
      for Auxin-Mediated Cell Polarity and Patterning in Arabidopsis.
AB  - Cell polarity manifested by asymmetric distribution of cargoes, such as receptors
      and transporters, within the plasma membrane (PM) is crucial for essential
      functions in multicellular organisms. In plants, cell polarity (re)establishment
      is intimately linked to patterning processes. Despite the importance of cell
      polarity, its underlying mechanisms are still largely unknown, including the
      definition and distinctiveness of the polar domains within the PM. Here, we show
      in Arabidopsis thaliana that the signaling membrane components, the
      phosphoinositides phosphatidylinositol 4-phosphate (PtdIns4P) and
      phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] as well as PtdIns4P 5
      kinases mediating their interconversion, are specifically enriched at apical and
      basal polar plasma membrane domains. The PtdIns4P 5-kinases PIP5K1 and PIP5K2 are
      redundantly required for polar localization of specifically apical and basal
      cargoes, such as PIN-FORMED transporters for the plant hormone auxin. As a
      consequence of the polarity defects, instructive auxin gradients as well as
      embryonic and postembryonic patterning are severely compromised. Furthermore,
      auxin itself regulates PIP5K transcription and PtdIns4P and PtdIns(4,5)P2 levels,
      in particular their association with polar PM domains. Our results provide
      insight into the polar domain-delineating mechanisms in plant cells that depend
      on apical and basal distribution of membrane lipids and are essential for
      embryonic and postembryonic patterning.

PMID- 24876259
TI  - Vitamin K antagonists and risk of subdural hematoma: meta-analysis of randomized
      clinical trials.
AB  - BACKGROUND AND PURPOSE: Subdural hematomas are an important bleeding complication
      of anticoagulation. We quantify the risk of subdural hematoma associated with
      anticoagulation with vitamin K antagonists (VKAs) compared with other oral
      antithrombotic therapies. METHODS: Randomized trials were identified from the
      Cochrane Central Register of Controlled Trials and were included if published
      since 1980 and compared oral VKAs with antiplatelet therapy or with direct-acting
      oral anticoagulants. Two reviewers independently extracted data with differences
      resolved by joint review. RESULTS: Nineteen randomized trials were included that
      involved 92 156 patients and 275 subdural hematomas. By meta-analysis, VKAs were
      associated with a significantly increased risk of subdural hematoma (odds ratios,
      3.0; 95% confidence interval, 1.5-6.1) compared with antiplatelet therapy (9
      trials, 11 603 participants). The risk of subdural hematoma was also
      significantly higher with VKAs versus factor Xa inhibitors (meta-analysis odds
      ratios, 2.9; 95% confidence interval, 2.1-4.1; 5 trials, 49 687 patients) and
      direct thrombin inhibitors (meta-analysis odds ratios, 1.8; 95% confidence
      interval, 1.2-2.7; 5 trials, 30 866 patients) versus VKAs. The absolute rate of
      subdural hematoma among 24 485 patients with atrial fibrillation treated with
      VKAs pooled from 6 trials testing direct-acting oral anticoagulants was 2.9 (95%
      confidence interval, 2.5-3.5) per 1000 patient-years. CONCLUSIONS: VKA use
      significantly increases the risk of subdural hematoma by ~3-fold relative to
      antiplatelet therapy. Direct-acting oral anticoagulants are associated with a
      significantly reduced risk of subdural hematomas versus VKAs. Based on indirect
      comparisons to VKAs, the risks of subdural hematoma are similar with antiplatelet
      monotherapies and factor Xa inhibitors.

PMID- 24876260
TI  - Comparison of computed tomographic and magnetic resonance perfusion measurements
      in acute ischemic stroke: back-to-back quantitative analysis.
AB  - BACKGROUND AND PURPOSE: Magnetic resonance perfusion (MRP) and computed
      tomographic perfusion (CTP) are being increasingly applied in acute stroke trials
      and clinical practice, yet the comparability of their perfusion values is not
      well validated. The aim of this study was to validate the comparability of CTP
      and MRP measures. METHODS: A 3-step approach was used. Step 1 was a derivation
      step, where we analyzed 45 patients with acute ischemic stroke who had both CTP
      and MRP performed within 2 hours of each other and within 9 hours of stroke
      onset. In this step, we derived the optimal perfusion map with the least
      difference between MRP and CTP. In step 2, the optimal map was validated on whole
      brain perfusion data of 15 patients. Step 3 was to apply the optimal perfusion
      map to define cross-modality reperfusion from acute CTP to 24-hour MRP in 45
      patients and, in turn, to assess how accurately this predicted 3-month clinical
      outcome. RESULTS: Among 8 different perfusion maps included in this study, time
      to peak of the residual function (T(max)) was the only one with a nonsignificant
      difference between CTP and MRP in delineating perfusion defects. This was
      validated on whole-brain perfusion data, showing high concordance of T(max)
      between the 2 modalities (concordance correlation coefficient of Lin, >0.91); the
      best concordance was at 6 s. At T(max)>6 s threshold, MRP and CTP reached
      substantial agreement in mismatch classification (kappa >0.61). Cross-modality
      reperfusion calculated by T(max)>6 s strongly predicted good functional outcome
      at 3 months (area under the curve, 0.979; P<0.05). CONCLUSIONS: MRP and CTP can
      be used interchangeably if one uses T(max) measurement.

PMID- 24876262
TI  - Postacute stromal cell-derived factor-1alpha expression promotes neurovascular
      recovery in ischemic mice.
AB  - BACKGROUND AND PURPOSE: Acute interventions of stroke are often challenged by a
      narrow treatment window. In this study, we explore treatments in the postacute
      phase of stroke with wider windows of opportunity. We investigated the effects of
      stromal cell-derived factor (SDF-1alpha) in neurovascular recovery during the
      postacute phase and downstream signaling pathways, underlying SDF-1alpha-mediated
      neurovascular recovery. METHODS: Adult male Institute of Cancer Research (ICR)
      mice underwent middle cerebral artery occlusion. One week after middle cerebral
      artery occlusion, the animals received stereotactic injection of adenoassociated
      virus (AAV) carrying SDF-1alpha gene as treatment or AAV-green fluorescent
      protein as control and were monitored for 5 weeks. Neurobehavioral outcomes were
      evaluated, and brain atrophy was measured. Neurogenesis and angiogenesis were
      examined. The proliferation and migration of neural progenitor cells were
      evaluated. Downstream pathways of SDF-1alpha were investigated. Inflammatory
      response was monitored. RESULTS: Neurobehavioral outcomes were improved, and
      brain atrophy was greatly reduced for <=5 weeks in AAV-SDF-1alpha groups when
      compared with the control. SDF-1 receptor CXCR4 was upregulated and colocalized
      with neural and endothelial progenitor cells. The number of nestin(+) and
      doublecortin(+)/bromodeoxyuridine(+) cells in the subventricular zone,
      doublecortin(+) and neuron(+)/bromodeoxyuridine(+) cells in the perifocal region,
      and cluster of differentiation (CD)31(+) and bromodeoxyuridine(+)/CD31(+)
      microvessels are also significantly increased in AAV-SDF-1alpha groups.
      Administration of CXCR4 antagonist AMD3100 eliminated the beneficial effects of
      SDF-1alpha. SDF-1alpha/CXCR4 interaction activated AKT, extracellular signal
      regulated kinases (ERK), and P38 mitogen-activated protein kinase (MAPK)
      signaling pathways but not the c-Jun N-terminal kinase (JNK) pathway.
      CONCLUSIONS: SDF-1alpha promoted neurogenesis and angiogenesis during the
      postacute phase of ischemia without eliciting an inflammatory response. AAV-SDF
      1alpha expression represents a promising avenue for ischemic stroke therapy with
      a wider treatment window.

PMID- 24876265
TI  - Effect of English proficiency and research funding on acceptance of submitted
      articles to stroke journal.

PMID- 24876263
TI  - Migraine, white matter hyperintensities, and subclinical brain infarction in a
      diverse community: the northern Manhattan study.
AB  - BACKGROUND AND PURPOSE: Migraine with aura is a risk factor for ischemic stroke.
      The goals of this study are to examine the association between migraine and
      subclinical cerebrovascular damage in a race/ethnically diverse older population
      based cohort study. METHODS: In the Northern Manhattan Study (NOMAS), we
      quantified subclinical brain infarctions and white matter hyperintensity volumes
      among participants with self-reported migraine, confirmed by the International
      Classification of Headache Disorders-2 criteria. RESULTS: Of 546 study
      participants with imaging and migraine data (41% men; mean age at MRI, 71+/-8
      years; mostly Hispanic [65%]), those reporting migraine overall had double the
      odds of subclinical brain infarction (adjusted odds ratio, 2.1; 95% confidence
      interval, 1.0-4.2) when compared with those reporting no migraine, after
      adjusting for sociodemographics and vascular risk factors. No association was
      observed between migraine with or without aura and white matter hyperintensity
      volume. CONCLUSIONS: Migraine may be a risk factor for subclinical brain
      infarction. Prospective studies are needed in race/ethnically diverse
      populations.

PMID- 24876266
TI  - Organizational update: American Heart Association Stroke Council.

PMID- 24876264
TI  - Risk factors for computed tomography angiography spot sign in deep and lobar
      intracerebral hemorrhage are shared.
AB  - BACKGROUND AND PURPOSE: Patients with intracerebral hemorrhage (ICH) who present
      with a spot sign on computed tomography angiography are at increased risk of
      hematoma expansion and poor outcome. Because primary ICH is the acute
      manifestation of chronic cerebral small vessel disease, we investigated whether
      different clinical or imaging characteristics predict spot sign presence, using
      ICH location as a surrogate for arteriolosclerosis- and cerebral amyloid
      angiopathy-related ICH. METHODS: Patients with primary ICH and available computed
      tomography angiography at presentation were included. Predictors of spot sign
      were assessed using uni- and multivariable regression, stratified by ICH
      location. RESULTS: Seven hundred forty-one patients were eligible, 335 (45%) deep
      and 406 (55%) lobar ICH. At least one spot sign was present in 76 (23%) deep and
      102 (25%) lobar ICH patients. In multivariable regression, warfarin (odds ratio
      [OR], 2.42; 95% confidence interval [CI], 1.01-5.71; P=0.04), baseline ICH volume
      (OR, 1.20; 95% CI, 1.09-1.33, per 10 mL increase; P<0.001), and time from symptom
      onset to computed tomography angiography (OR, 0.89; 95% CI, 0.80-0.96, per hour;
      P=0.009) were associated with the spot sign in deep ICH. Predictors of spot sign
      in lobar ICH were warfarin (OR, 3.95; 95% CI, 1.87-8.51; P<0.001) and baseline
      ICH volume (OR, 1.20; 95% CI, 1.10-1.31, per 10 mL increase; P<0.001).
      CONCLUSIONS: The most potent associations with spot sign are shared between deep
      and lobar ICH, suggesting that the acute bleeding process that arises in the
      setting of different chronic small vessel diseases shares commonalities.

PMID- 24876268
TI  - Time for a sugary drinks tax in the UK?

PMID- 24876261
TI  - Drivers of costs associated with reperfusion therapy in acute stroke: the
      Interventional Management of Stroke III Trial.
AB  - BACKGROUND AND PURPOSE: The Interventional Management of Stroke (IMS) III study
      tested the effect of intravenous tissue-type plasminogen activator (tPA) alone
      when compared with intravenous tPA followed by endovascular therapy and collected
      cost data to assess the economic implications of the 2 therapies. This report
      describes the factors affecting the costs of the initial hospitalization for
      acute stroke subjects from the United States. METHODS: Prospective cost analysis
      of the US subjects was treated with intravenous tPA alone or with intravenous tPA
      followed by endovascular therapy in the IMS III trial. Results were compared with
      expected Medicare payments. RESULTS: The adjusted cost of a stroke admission in
      the study was $35 130 for subjects treated with endovascular therapy after
      intravenous tPA treatment and $25 630 for subjects treated with intravenous tPA
      alone (P<0.0001). Significant factors related to costs included treatment group,
      baseline National Institutes of Health Stroke Scale, time from stroke onset to
      intravenous tPA, age, stroke location, and comorbid diabetes mellitus. The mean
      cost for subjects who had routine use of general anesthesia as part of
      endovascular therapy was $46 444 when compared with $30 350 for those who did not
      have general anesthesia. The costs of embolectomy for IMS III subjects and
      patients from the National Inpatient Sample cohort exceeded the Medicare
      diagnosis-related group payment in >=75% of patients. CONCLUSIONS: Minimizing the
      time to start of intravenous tPA and decreasing the use of routine general
      anesthesia may improve the cost-effectiveness of medical and endovascular therapy
      for acute stroke. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov.
      Unique identifier: NCT00359424.

PMID- 24876269
TI  - Promoting resilience in adults with experience of intimate partner violence or
      child maltreatment: a narrative synthesis of evidence across settings.
AB  - BACKGROUND: People who have experienced intimate partner violence (IPV) or child
      maltreatment (CM) are at risk of having lower resilience and adverse
      psychological outcomes. In keeping with the social and environmental factors that
      support resilience, there is a need to take a public health approach to its
      investigation and to identify existing initiatives in particular settings and
      populations that can guide its deliberate promotion. METHOD: This narrative
      synthesis examines quantitative and qualitative studies of interventions with
      resilience-related outcomes in specified health and other settings. Clinical RCTs
      are excluded as beyond the scope of this review. RESULTS: Twenty studies were
      identified for review in several settings, consisting of 14 quantitative studies,
      2 review studies, 2 qualitative studies and 2 mixed-methods studies. Three
      quantitative studies produced strong evidence to support: a home visitation
      program for at-risk mothers; a methadone program for women and a substance abuse
      program. This review reveals that few studies use specific resilience measures.
      CONCLUSIONS: The topic has been little studied despite high needs for public
      health interventions in countries of all types. Interventions and research
      studies that use specific resilience measures are likely to help measure and
      integrate what is currently a disparate area. IMPLICATIONS: The participation of
      people with IPV or CM history in program and research design and implementation
      is indicated to support advocacy, innovation and sustainable interventions. This
      is especially pertinent for interventions in LAMIC and indigenous settings where
      continuing programs are sorely needed.

PMID- 24876270
TI  - How good is compliance with smoke-free legislation in India? Results of 38
      subnational surveys.
AB  - BACKGROUND: India has been implementing smoke-free legislation since 2008
      prohibiting smoking in public places. This study aimed to assess the level of
      compliance with smoke-free legislation (defined as the presence of no-smoking
      signage and the absence of active smoking, smoking aids, cigarette butts/bidi
      ends and smoking smell) and the role of enforcement systems in Indian
      jurisdictions. METHODS: This was a cross-sectional, retrospective review of
      reports and primary data sheets of surveys conducted in 38 selected jurisdictions
      across India in 2012-2013. RESULTS: Of 20 455 public places (in 38
      jurisdictions), 10 377 (51%) demonstrated full compliance with smoke-free law.
      Educational institutions and healthcare facilities performed well at 65% and 62%,
      respectively, while eateries and frequently visited other public places (such as
      bus stands, railway stations, shopping malls, stadia, cinema halls etc.)
      performed poorly at 37% and 27%, respectively. Absence of no-smoking signage was
      the largest contributor to non-compliance across all types of public places.
      Enforcement systems were present in all jurisdictions, but no associations could
      be demonstrated between these and smoke-free compliance. CONCLUSION: Smoke-free
      compliance in public places in India was suboptimal and was mainly related to the
      absence of no-smoking signage. This warrants further pragmatic and innovative
      ways to improve the situation.

PMID- 24876272
TI  - Titan solar occultation observations reveal transit spectra of a hazy world.
AB  - High-altitude clouds and hazes are integral to understanding exoplanet
      observations, and are proposed to explain observed featureless transit spectra.
      However, it is difficult to make inferences from these data because of the need
      to disentangle effects of gas absorption from haze extinction. Here, we turn to
      the quintessential hazy world, Titan, to clarify how high-altitude hazes
      influence transit spectra. We use solar occultation observations of Titan's
      atmosphere from the Visual and Infrared Mapping Spectrometer aboard National
      Aeronautics and Space Administration's (NASA) Cassini spacecraft to generate
      transit spectra. Data span 0.88-5 MUm at a resolution of 12-18 nm, with
      uncertainties typically smaller than 1%. Our approach exploits symmetry between
      occultations and transits, producing transit radius spectra that inherently
      include the effects of haze multiple scattering, refraction, and gas absorption.
      We use a simple model of haze extinction to explore how Titan's haze affects its
      transit spectrum. Our spectra show strong methane-absorption features, and weaker
      features due to other gases. Most importantly, the data demonstrate that high
      altitude hazes can severely limit the atmospheric depths probed by transit
      spectra, bounding observations to pressures smaller than 0.1-10 mbar, depending
      on wavelength. Unlike the usual assumption made when modeling and interpreting
      transit observations of potentially hazy worlds, the slope set by haze in our
      spectra is not flat, and creates a variation in transit height whose magnitude is
      comparable to those from the strongest gaseous-absorption features. These
      findings have important consequences for interpreting future exoplanet
      observations, including those from NASA's James Webb Space Telescope. 

PMID- 24876271
TI  - RBE and OER within the spread-out Bragg peak for proton beam therapy: in vitro
      study at the Proton Medical Research Center at the University of Tsukuba.
AB  - There are few reports on the biological homogeneity within the spread-out Bragg
      peak (SOBP) of proton beams. Therefore, to evaluate the relative biological
      effectiveness (RBE) and the oxygen enhancement ratio (OER), human salivary gland
      tumor (HSG) cells were irradiated at the plateau position (position A) and three
      different positions within a 6-cm-wide SOBP (position B, 26 mm proximal to the
      middle; position C, middle; position D, 26 mm distal to the middle) using 155
      MeV/n proton beams under both normoxic and hypoxic conditions at the Proton
      Medical Research Center, University of Tsukuba, Japan. The RBE to the plateau
      region (RBE(plateau)) and the OER value were calculated from the doses
      corresponding to 10% survival data. Under the normoxic condition, the
      RBE(plateau) was 1.00, 0.99 and 1.09 for positions B, C and D, respectively.
      Under the hypoxic condition, the RBE(plateau) was 1.10, 1.06 and 1.12 for
      positions B, C and D, respectively. The OER was 2.84, 2.60, 2.63 and 2.76 for
      positions A, B, C and D, respectively. There were no significant differences in
      either the RBE(plateau) or the OER between these three positions within the SOBP.
      In conclusion, biological homogeneity need not necessarily be taken into account
      for treatment planning for proton beam therapy at the University of Tsukuba.

PMID- 24876274
TI  - Function determines structure in complex neural networks.

PMID- 24876273
TI  - Targeting RPL39 and MLF2 reduces tumor initiation and metastasis in breast cancer
      by inhibiting nitric oxide synthase signaling.
AB  - We previously described a gene signature for breast cancer stem cells (BCSCs)
      derived from patient biopsies. Selective shRNA knockdown identified ribosomal
      protein L39 (RPL39) and myeloid leukemia factor 2 (MLF2) as the top candidates
      that affect BCSC self-renewal. Knockdown of RPL39 and MLF2 by specific siRNA
      nanoparticles in patient-derived and human cancer xenografts reduced tumor volume
      and lung metastases with a concomitant decrease in BCSCs. RNA deep sequencing
      identified damaging mutations in both genes. These mutations were confirmed in
      patient lung metastases (n = 53) and were statistically associated with shorter
      median time to pulmonary metastasis. Both genes affect the nitric oxide synthase
      pathway and are altered by hypoxia. These findings support that extensive tumor
      heterogeneity exists within primary cancers; distinct subpopulations associated
      with stem-like properties have increased metastatic potential. 

PMID- 24876275
TI  - Existing cardiomyocytes generate cardiomyocytes at a low rate after birth in
      mice.
AB  - The mammalian heart has long been considered a postmitotic organ, implying that
      the total number of cardiomyocytes is set at birth. Analysis of cell division in
      the mammalian heart is complicated by cardiomyocyte binucleation shortly after
      birth, which makes it challenging to interpret traditional assays of cell
      turnover [Laflamme MA, Murray CE (2011) Nature 473(7347):326-335; Bergmann O, et
      al. (2009) Science 324(5923):98-102]. An elegant multi-isotope imaging-mass
      spectrometry technique recently calculated the low, discrete rate of
      cardiomyocyte generation in mice [Senyo SE, et al. (2013) Nature 493(7432):433
      436], yet our cellular-level understanding of postnatal cardiomyogenesis remains
      limited. Herein, we provide a new line of evidence for the differentiated alpha
      myosin heavy chain-expressing cardiomyocyte as the cell of origin of postnatal
      cardiomyogenesis using the "mosaic analysis with double markers" mouse model. We
      show limited, life-long, symmetric division of cardiomyocytes as a rare event
      that is evident in utero but significantly diminishes after the first month of
      life in mice; daughter cardiomyocytes divide very seldom, which this study is the
      first to demonstrate, to our knowledge. Furthermore, ligation of the left
      anterior descending coronary artery, which causes a myocardial infarction in the
      mosaic analysis with double-marker mice, did not increase the rate of
      cardiomyocyte division above the basal level for up to 4 wk after the injury. The
      clonal analysis described here provides direct evidence of postnatal mammalian
      cardiomyogenesis. 

PMID- 24876276
TI  - HLA-B*51 the primary risk in Behcet disease.

PMID- 24876277
TI  - Assessing what is cultural about Asian Americans' academic advantage.

PMID- 24876278
TI  - Protease-activated receptor 2 (PAR2) is upregulated by Acanthamoeba plasminogen
      activator (aPA) and induces proinflammatory cytokine in human corneal epithelial
      cells.
AB  - PURPOSE: Acanthamoeba plasminogen activator (aPA) is a serine protease elaborated
      by Acanthamoeba trophozoites that facilitates the invasion of trophozoites to the
      host and contributes to the pathogenesis of Acanthamoeba keratitis (AK). The aim
      of this study was to explore if aPA stimulates proinflammatory cytokine in human
      corneal epithelial (HCE) cells via the protease-activated receptors (PARs)
      pathway. METHODS: Acanthamoeba castellanii trophozoites were grown in peptone
      yeast extract glucose for 7 days, and the supernatants were collected and
      centrifuged. The aPA was purified using the fast protein liquid chromatography
      system, and aPA activity was determined by zymography assays. Human corneal
      epithelial cells were incubated with or without aPA (100 MUg/mL), PAR1 agonists
      (thrombin, 10 MUM; TRAP-6, 10 MUM), and PAR2 agonists (SLIGRL-NH2, 100 MUM; AC
      55541, 10 MUM) for 24 and 48 hours. Inhibition of PAR1 and PAR2 involved
      preincubating the HCE cells for 1 hour with the antagonist of PAR1 (SCH 79797, 60
      MUM) and PAR2 (FSLLRY-NH2, 100 MUM) with or without aPA. Human corneal epithelial
      cells also were preincubated with PAR1 and PAR2 antagonists and then incubated
      with or without PAR1 agonists (thrombin and TRAP-6) and PAR2 agonists (SLIGRL-NH2
      and AC 55541). Expression of PAR1 and PAR2 was examined by quantitative RT-PCR
      (qRT-PCR), flow cytometry, and immunocytochemistry. Interleukin-8 expression was
      quantified by qRT-PCR and ELISA. RESULTS: Human corneal epithelial cells
      constitutively expressed PAR1 and PAR2 mRNA. Acanthamoeba plasminogen activator
      and PAR2 agonists significantly upregulated PAR2 mRNA expression (1- and 2-fold,
      respectively) (P < 0.05). Protease-activated receptor 2 antagonist significantly
      inhibited aPA, and PAR2 agonists induced PAR2 mRNA expression in HCE cells (P <
      0.05). Protease-activated receptor 1 agonists, but not aPA, significantly
      upregulated PAR1 mRNA expression, which was significantly inhibited by PAR1
      antagonist in HCE cells. Acanthamoeba plasminogen activator and PAR2 agonists
      stimulated IL-8 mRNA expression and protein production, which is significantly
      diminished by PAR2 antagonist (P < 0.05). Protease-activated receptor 1
      antagonist did not alter aPA-stimulated IL-8 mRNA expression and protein
      production in HCE cells. Flow cytometry and immunocytochemistry showed that aPA
      and SLIGRL-NH2 (PAR2 agonist) upregulated PAR2 surface protein as compared to
      that in unstimulated HCE cells. Thrombin, but not aPA, stimulated PAR1 surface
      protein in HCE cells. CONCLUSIONS: Acanthamoeba plasminogen activator
      specifically induces expression and production of IL-8 in HCE cells via PAR2
      pathway, and PAR2 antagonists may be used as a therapeutic target in AK.

PMID- 24876280
TI  - MMP-2, MMP-3, TIMP-1, TIMP-2, and TIMP-3 protein levels in human aqueous humor:
      relationship with axial length.
AB  - PURPOSE: We measured the aqueous humor levels of matrix metalloproteinases (MMP)
      MMP-1, MMP-2, MMP-3, and tissue inhibitors of matrix metalloproteinases (TIMP)
      TIMP-1, TIMP-2, and TIMP-3 in patients with myopia or cataract, and investigated
      the relationship between their levels and axial length (AL). METHODS: We measured
      MMP/TIMPs levels with the Luminex xMAP Technology by using commercially available
      Milliplex xMAP Kits. A total of 65 aqueous humor samples was collected from
      patients with myopia or cataract during cataract or clear lens extraction
      surgery. According to the AL, the samples were divided into three groups: group
      A, AL <= 24 mm; group B, AL 24 to 26 mm; and group C, AL >= 26 mm. RESULTS:
      Levels of MMP-2, MMP-3, TIMP-1, TIMP-2, and TIMP-3 could be detected in the
      aqueous humor. The levels of MMP-2, TIMP-1, TIMP-2, and TIMP-3 were positively
      correlated with AL. The differences of the levels of these MMPs/TIMPs among the
      three groups were statistically significant. The MMP-3 levels were not correlated
      with AL and there was no significant difference in MMP-3 levels among these three
      groups. Levels of MMP-1 could not be detected in the aqueous humor samples.
      CONCLUSIONS: Elevated levels of aqueous MMP-2, TIMP-1, TIMP-2, and TIMP-3 were
      found in the eyes with elongated axis.

PMID- 24876281
TI  - Reproducibility of anterior chamber angle analyses with the swept-source optical
      coherence tomography in young, healthy Caucasians.
AB  - PURPOSE: To assess the reproducibility of iridocorneal angle (ICA) analysis in
      young, healthy Caucasian subjects using swept-source optical coherence tomography
      (SS-OCT) by determining variability and interobserver agreement between expert
      and nonexpert observers. METHODS: Thirty-one healthy volunteers (nonexperts)
      acquired three consecutive SS-OCT images of the right eyes of their peer
      nonexperts. Images were analyzed by 31 nonexperts and additionally by three
      experts, whereby the angle opening distance (AOD) and the trabecular iris space
      area (TISA) at 500 and 750 MUm were calculated. A random intercept model was used
      to determine the amount of variation between observers. In addition, the intra
      observer variability between nonexperts and experts was calculated by determining
      the coefficient of variation (CV). RESULTS: A significant difference was found in
      the expert analysis for the nasal and temporal angle in the AOD500 (P = 0.002),
      AOD750 (P < 0.01), and TISA750 (P < 0.01), and the values AOD500 (P = 0.025),
      AOD750 (P = 0.012), and TISA500 (P = 0.010) were significantly larger if
      nonexperts analyzed SS-OCT images. The CV was only significant larger for
      nonexperts for AOD500 (11.1% vs. 8.7%, P < 0.01). CONCLUSIONS: This study
      demonstrated high reproducibility of angle analysis in young, healthy Caucasian
      subjects using SS-OCT. Nevertheless, nonexperts obtained significant larger
      values compared with experts, implying that training is a necessary requirement
      before analyzing SS-OCT images in ophthalmic practice.

PMID- 24876279
TI  - IMPG2-associated retinitis pigmentosa displays relatively early macular
      involvement.
AB  - PURPOSE: To provide the first detailed clinical description in patients with RP
      caused by recessive mutations in IMPG2. METHODS: This international collaborative
      study includes 17 RP patients with inherited retinal disease caused by mutations
      in IMPG2. The patients were clinically (re-)examined, including extensive medical
      history taking, slit-lamp biomicroscopy, ophthalmoscopy, perimetry, ERG, optical
      coherence tomography (OCT), fundus autofluorescence (FAF) imaging, fundus
      photography, and color vision tests. The main outcome measures included mean age
      at onset, initial symptom, best-corrected visual acuity, fundus appearance,
      perimetry results, ERG responses, OCT images, FAF imaging, color vision test
      reports and DNA sequence variants. RESULTS: The mean age at onset was 10.5 years
      (range, 4-20 years). Initial symptoms included night blindness in 59% of
      patients, a decreased visual acuity in 35%, and visual field loss in 6%. Fundus
      abnormalities were typical of RP: optic disc pallor, attenuated vessels, bone
      spicules, and generalized atrophy of the retina and choriocapillaris.
      Additionally, we observed macular abnormalities in all patients, ranging from
      subtle mottling of the macular pigment epithelium (two patients) and a bull's eye
      maculopathy (seven patients) to macular chorioretinal atrophy (seven patients).
      CONCLUSIONS: Mutations in IMPG2 cause a severe form of RP with symptoms
      manifesting in the first 2 decades of life. IMPG2-associated RP is frequently
      accompanied by macular involvement, ranging from mild pigment alterations to
      profound chorioretinal atrophy. The resulting decrease in central vision in
      combination with the severe tunnel vision leads to severe visual impairment in
      patients with IMPG2-associated RP.

PMID- 24876282
TI  - Higher-order aberrations of anterior and posterior corneal surfaces in patients
      with keratectasia after LASIK.
AB  - PURPOSE: We investigated higher-order aberrations (HOAs) of the anterior and
      posterior corneal surfaces in patients with keratectasia after LASIK. METHODS:
      The subjects comprised four groups: 12 eyes with keratectasia after LASIK, 30
      eyes following LASIK without keratectasia, 30 keratoconic eyes, and 30 normal
      eyes. Corneal HOAs due to the anterior and posterior corneal surfaces for 6-mm
      pupils (root mean square [MUm]) were obtained using a Scheimpflug-based corneal
      tomographer and compared among the four groups. RESULTS: There were significant
      differences in total HOAs of the anterior and posterior corneal surfaces (mean +/
      SD) in the keratectasia (2.49 +/- 1.37 and 0.83 +/- 0.57), keratoconus (4.50 +/-
      2.57 and 1.18 +/- 0.65), LASIK (0.84 +/- 0.25 and 0.14 +/- 0.04), and normal
      (0.52 +/- 0.15 and 0.17 +/- 0.06) groups except for between keratoconus and
      keratectasia at the posterior surface. Keratectasia and keratoconus showed
      similar coma-dominant patterns at both surfaces, and there were no significant
      differences in the Zernike terms between both groups except for the total HOAs
      and coma aberration at the anterior surface. CONCLUSIONS: Although flap creation
      and laser ablation were supposed to center on the primary line of sight in LASIK,
      keratectasia after LASIK showed coma-dominant HOAs at both corneal surfaces. This
      suggests that the cornea in keratectasia has optical properties similar to those
      in keratoconus.

PMID- 24876283
TI  - Relative flow volume, a novel blood flow index in the human retina derived from
      laser speckle flowgraphy.
AB  - PURPOSE: We investigated the accuracy and reproducibility of relative flow volume
      (RFV), a novel index of blood flow in the human retina derived from laser speckle
      flowgraphy (LSFG). METHODS: Pre- and postbranch retinal RFV measurements were
      compared in 34 retinal venous bifurcations in 34 healthy volunteers (mean age,
      49.0 +/- 14.8 years) to determine the accuracy of RFV. Next, the coefficient of
      variation (COV) of RFV was determined for 30 temporal retinal arteries in a
      second group of 18 healthy volunteers (mean age, 30.3 +/- 7.7 years). Finally,
      laser Doppler velocimetry (LDV) data were obtained from the same study population
      and compared to RFV data from the retinal vessels. RESULTS: A comparison of RFV
      measurements in a trunk vessel of the retina and the sum of its two daughter
      vessels revealed a strong correlation (r = 0.98, P < 0.001). Reproducibility
      analysis showed that the COV for RFV was 5.9% +/- 3.6%. Linear regression
      analysis revealed that RFV was correlated significantly with LDV measurements of
      mean retinal blood velocity (vmean) and retinal blood flow (FLDV, vmean, r =
      0.61, P < 0.001; FLDV, r = 0.51, P = 0.004, respectively), but not significantly
      correlated with ocular perfusion pressure (r = -0.04, P = 0.76). CONCLUSIONS:
      These results suggest that RFV values obtained with LSFG can be considered an
      accurate and reliable index of relative blood flow in the human retina. Thus,
      RFV, a novel LSFG-derived variable, has potential for assessing retinal blood
      flow alterations in ocular disease.

PMID- 24876285
TI  - Intraocular pressure and associated factors in children: the Shandong children
      eye study.
AB  - PURPOSE: We examined the distribution of intraocular pressure (IOP) and its
      associated factors in children. METHODS: Using a random cluster sampling from
      kindergartens, primary schools, and junior and senior high schools from rural
      Guanxian County and the city of Weihai, the school-based cross-sectional Shandong
      Children Eye Study included children aged 4 to 18 years. All participants
      underwent an ocular examination, including ocular biometry, cycloplegic
      refractometry, and noncontact tonometry. RESULTS: Mean IOP was 17.6 +/- 2.7 mm Hg
      (range, 10-28 mm Hg). The IOP increased up to an age of 10 years and subsequently
      decreased with older age. In multivariate regression analysis, higher IOP was
      associated with female sex (P < 0.001; standardized correlation coefficient beta,
      0.06; regression coefficient beta, 0.34; 95% confidence interval [CI], 0.18,
      0.50), higher body mass index (P < 0.001; correlation coefficient beta, 0.09;
      regression coefficient beta, 0.07; 95% CI, 0.04,0.09), younger age (P < 0.001;
      correlation coefficient beta, -0.15; regression coefficient beta, -0.13; 95% CI, 
      0.17,-0.10), maternal myopia (P < 0.001; correlation coefficient beta, 0.05;
      regression coefficient beta, 0.34; 95% CI, 0.15,0.53), and more time spent
      indoors with reading/writing (P = 0.002; correlation coefficient beta, 0.05;
      regression coefficient beta, 0.07; 95% CI, 0.03,0.11), and with the ocular
      parameters of longer axial length (P < 0.001; correlation coefficient beta, 0.14;
      regression coefficient beta, 0.29; 95% CI, 0.21,0.37) and smaller corneal
      horizontal diameter (P < 0.001; correlation coefficient beta, -0.06; regression
      coefficient beta, -0.31; 95% CI, -0.46,-0.15). CONCLUSIONS: In children aged 4 to
      18 years, IOP showed an M-shaped association with age. Higher IOP was associated
      with the nonocular parameters of female sex (P < 0.001), higher body mass index
      (P < 0.001), younger age (P < 0.001), maternal myopia (P < 0.001), and more time
      spent indoors with reading/writing (P = 0.002), and with the ocular parameters of
      longer axial length (P < 0.001) and smaller corneal horizontal diameter (P <
      0.001).

PMID- 24876287
TI  - Surface properties of artificial tear film lipid layers: effects of wax esters.
AB  - PURPOSE: The tear film lipid layer is believed to stabilize the tear film and to
      retard evaporation. Based on previous simple in vitro studies, the evidence for
      the latter property is scarce. In this study, we used complex lipid mixtures
      including various wax esters to study their physical properties and evaporation
      retarding effect. METHODS: Twelve samples of artificial tear film lipid layer
      mixtures composed of (L-alpha)-phosphatidylcholine, cholesterol oleate, and
      triglycerides were mixed with wax esters. A Langmuir balance was used to analyze
      the compressibility and rheological properties of these mixtures. In addition, a
      custom-built system was used for the evaporation studies used at 35 degrees C.
      Lipid films were imaged with Brewster angle microscopy. RESULTS: None of the
      studied lipid mixtures decreased the evaporation rate. All lipid mixtures had
      similar compression isotherms and viscoelastic properties regardless of the wax
      ester species or its concentration. The results suggest that the overall
      properties of these mixtures are independent of individual lipid species and that
      these films are very cooperative and showed minor variation depending on the wax
      ester species. Brewster angle microscopy images revealed that the lipid films
      assembled into multiple layers. CONCLUSIONS: Wax ester-containing lipid mixtures
      resembling the tear film lipid layer are organized in a layered fashion so that
      amphiphilic lipids are adjacent to the aqueous phase and the nonpolar lipids are
      layered on top of these. This organization does not retard evaporation and raises
      overall questions about the role of lipids in the tear film.

PMID- 24876286
TI  - Multipurpose care solution-induced corneal surface disruption and Pseudomonas
      aeruginosa internalization in the rabbit corneal epithelium.
AB  - PURPOSE: To evaluate the effects of a chemically preserved multipurpose contact
      lens care solution (MPS) on the corneal epithelial surface and Pseudomonas
      aeruginosa (PA) internalization in the rabbit corneal epithelium. METHODS:
      Rabbits were fit in one eye with a silicone hydrogel lens (balafilcon A) soaked
      overnight in a borate-buffered MPS (BioTrue). The contralateral eye was fit with
      a lens removed directly from the blister pack containing borate-buffered saline
      (control). Lenses were worn for 2 hours. Upon lens removal, corneas were
      challenged ex vivo with invasive PA strain 6487 and assessed for PA
      internalization. Ultrastructural changes were assessed using scanning electron
      (SEM) and transmission electron microscopy (TEM). RESULTS: Scanning electron
      microscopy showed frank loss of surface epithelium in MPS-exposed eyes, while
      control eyes exhibited occasional loss of surface membranes but retention of
      intact junctional borders. Transmission electron microscopy data supported and
      extended SEM findings, demonstrating the presence of epithelial edema in MPS
      treated eyes. There was a 12-fold increase in PA uptake into the corneal
      epithelium following wear of the MPS-treated lens compared to control (P =
      0.008). CONCLUSIONS: These data demonstrate that corneal exposure to MPS during
      lens wear damages the surface epithelium and are consistent with our previous
      clinical data showing an increase in bacterial binding to exfoliated epithelial
      cells following MPS use with resultant increased risk for lens-mediated
      infection. These findings also demonstrate that the PA invasion assay may provide
      a highly sensitive quantitative metric for assessing the physiological impact of
      lens-solution biocompatibility on the corneal epithelium.

PMID- 24876284
TI  - Intraocular pressure, blood pressure, and retinal blood flow autoregulation: a
      mathematical model to clarify their relationship and clinical relevance.
AB  - PURPOSE: This study investigates the relationship between intraocular pressure
      (IOP) and retinal hemodynamics and predicts how arterial blood pressure (BP) and
      blood flow autoregulation (AR) influence this relationship. METHODS: A
      mathematical model is developed to simulate blood flow in the central retinal
      vessels and retinal microvasculature as current flowing through a network of
      resistances and capacitances. Variable resistances describe active and passive
      diameter changes due to AR and IOP. The model is validated by using clinically
      measured values of retinal blood flow and velocity. The model simulations for six
      theoretical patients with high, normal, and low BP (HBP-, NBP-, LBP-) and
      functional or absent AR (-wAR, -woAR) are compared with clinical data. RESULTS:
      The model predicts that NBPwAR and HBPwAR patients can regulate retinal blood
      flow (RBF) as IOP varies between 15 and 23 mm Hg and between 23 and 29 mm Hg,
      respectively, whereas LBPwAR patients do not adequately regulate blood flow if
      IOP is 15 mm Hg or higher. Hemodynamic alterations would be noticeable only if
      IOP changes occur outside of the regulating range, which, most importantly,
      depend on BP. The model predictions are consistent with clinical data for IOP
      reduction via surgery and medications and for cases of induced IOP elevation.
      CONCLUSIONS: The theoretical model results suggest that the ability of IOP to
      induce noticeable changes in retinal hemodynamics depends on the levels of BP and
      AR of the individual. These predictions might help to explain the inconsistencies
      found in the clinical literature concerning the relationship between IOP and
      retinal hemodynamics.

PMID- 24876288
TI  - Aerobic exercise increases tear secretion in type 2 diabetic mice.
AB  - PURPOSE: To investigate the effects of exercise on tear secretion in type 2
      diabetic mice, and to investigate the effect of the adenosine monophosphate
      activated protein kinase (AMPK) activator 5-aminoimidazole-4-carboxamide
      ribonucleoside (AICAR). METHODS: Heterozygous controls (db/m; m Lepr(db)) and
      type 2 diabetic mice (db/db; Lepr(db)) either underwent forced treadmill exercise
      training 5 days a week or remained sedentary for 8 weeks. Tear secretion volume
      was measured by cotton threads for 30 seconds pre- and post intervention. The
      levels of oxidative stress markers (8-hydroxy-2'-deoxyguanosine [8-OHdG],
      propanoyl lysine [PRL], and hexanoyl lysine [HEL]) in tears were measured in the
      postintervention period. Furthermore, C57BL/6JJc1 mice, db/db mice, and db/m mice
      received a single intraperitoneal injection of AICAR or PBS each day for 5 days,
      and tear secretion volume was measured. RESULTS: Exercise training for 8 weeks
      increased tear secretion volume in db/m and db/db mice. The levels of oxidative
      stress markers in tears were less in the exercise group than in the control
      group. In C57BL/6JJc1 mice, the tear secretion volumes in both the AICAR 125
      mg/kg and AICAR 250 mg/kg groups were significantly larger than in the PBS group
      (P < 0.01 and P < 0.01, respectively). Additionally, in db/db mice, tear
      secretion volume in the AICAR 125 mg/kg group was also significantly larger than
      in the PBS group (P < 0.05). CONCLUSIONS: Exercise training for 8 weeks and a
      daily injection of AICAR for 5 days increased tear secretion in mice. The results
      suggest that exercise may be a potential therapy to modulate tear secretion.

PMID- 24876290
TI  - Taxes, prices and illicit trade: the need for sound evidence.

PMID- 24876289
TI  - Patient complaints in healthcare systems: a systematic review and coding
      taxonomy.
AB  - BACKGROUND: Patient complaints have been identified as a valuable resource for
      monitoring and improving patient safety. This article critically reviews the
      literature on patient complaints, and synthesises the research findings to
      develop a coding taxonomy for analysing patient complaints. METHODS: The PubMed,
      Science Direct and Medline databases were systematically investigated to identify
      patient complaint research studies. Publications were included if they reported
      primary quantitative data on the content of patient-initiated complaints. Data
      were extracted and synthesised on (1) basic study characteristics; (2)
      methodological details; and (3) the issues patients complained about. RESULTS: 59
      studies, reporting 88,069 patient complaints, were included. Patient complaint
      coding methodologies varied considerably (eg, in attributing single or multiple
      causes to complaints). In total, 113,551 issues were found to underlie the
      patient complaints. These were analysed using 205 different analytical codes
      which when combined represented 29 subcategories of complaint issue. The most
      common issues complained about were 'treatment' (15.6%) and 'communication'
      (13.7%). To develop a patient complaint coding taxonomy, the subcategories were
      thematically grouped into seven categories, and then three conceptually distinct
      domains. The first domain related to complaints on the safety and quality of
      clinical care (representing 33.7% of complaint issues), the second to the
      management of healthcare organisations (35.1%) and the third to problems in
      healthcare staff-patient relationships (29.1%). CONCLUSIONS: Rigorous analyses of
      patient complaints will help to identify problems in patient safety. To achieve
      this, it is necessary to standardise how patient complaints are analysed and
      interpreted. Through synthesising data from 59 patient complaint studies, we
      propose a coding taxonomy for supporting future research and practice in the
      analysis of patient complaint data.

PMID- 24876291
TI  - Effect of extending the photoperiod with low-intensity red or far-red light on
      the timing of shoot elongation and flower-bud formation of 1-year-old Japanese
      pear (Pyrus pyrifolia).
AB  - To investigate the effects of light quality (wavelength) on shoot elongation and
      flower-bud formation in Japanese pear (Pyrus pyrifolia (Burm. f.) Nakai), we
      treated 1-year-old trees with the following: (i) 8 h sunlight + 16 h dark (SD);
      (ii) 8 h sunlight + 16 h red light (LD(SD + R)); or (iii) 8 h sunlight + 16 h far
      red (FR) light (LD(SD + FR)) daily for 4 months from early April (before the
      spring flush) until early August in 2009 and 2010. In both years, shoot
      elongation stopped earlier in the LD(SD + FR) treatment than in the SD and LD(SD
      + R) treatments. After 4 months of treatments, 21% (2009) or 40% (2010) of LD(SD
      + FR)-treated trees formed flower buds in the shoot apices, whereas all the shoot
      apices from SD or LD(SD + R)-treated plants remained vegetative. With an
      additional experiment conducted in 2012, we confirmed that FR light at 730 nm was
      the most efficacious wavelength to induce flower-bud formation. Reverse
      transcription-quantitative polymerase chain reaction revealed that the expression
      of two floral meristem identity gene orthologues, LEAFY (PpLFY2a) and APETALA1
      (PpMADS2-1a), were up-regulated in the shoot apex of LD(SD + FR). In contrast,
      the expression of a flowering repressor gene, TERMINAL FLOWER 1 (PpTFL1-1a,
      PpTFL1-2a), was down-regulated. In addition, expression of an orthologue of the
      flower-promoting gene FLOWERING LOCUS T (PpFT1a) was positively correlated with
      flower-bud formation, although the expression of another orthologue, PpFT2a, was
      negatively correlated with shoot growth. Biologically active cytokinin and
      gibberellic acid concentrations in shoot apices were reduced with LD(SD + FR)
      treatment. Taken together, our results indicate that pear plants are able to
      regulate flowering in response to the R : FR ratio. Furthermore, LD(SD + FR)
      treatment terminated shoot elongation and subsequent flower-bud formation in the
      shoot apex at an earlier time, possibly by influencing the expression of
      flowering-related genes and modifying plant hormone concentrations.

PMID- 24876292
TI  - Wood biosynthesis and typologies: a molecular rhapsody.
AB  - Wood represents one of the most important renewable commodities for humanity and
      plays a crucial role in terrestrial ecosystem carbon-cycling. Wood formation is
      the result of a multitude of events that require the concerted action of
      endogenous and exogenous factors under the influence of photoperiod, for instance
      genes and plant growth regulators. Beyond providing mechanical support and being
      responsible for the increase in stem radial diameter, woody tissues constitute
      the vascular system of trees and are capable of reacting to environmental
      stimuli, and as such are therefore quite plastic and responsive. Despite the
      ecological and economic importance of wood, not all aspects of its formation have
      been unveiled. Many gaps in our knowledge are still present, which hinder the
      maximal exploitation of this precious bioresource. This review aims at surveying
      the current knowledge of wood formation and the available molecular data
      addressing the relationship between wood production and environmental factors,
      which have crucial influences on the rhythmic regulation of cambial activity and
      exert profound effects on tree stem growth, wood yield and properties. We will
      here go beyond wood sensu stricto, i.e., secondary xylem, and extend our survey
      to other tissues, namely vascular cambium, phloem and fibres. The purpose is to
      provide the reader with an overview of the complexity of the topic and to
      highlight the importance of progressing in the future towards an integrated
      knowledge on the subject. 

PMID- 24876293
TI  - Internal development of vegetative buds of Norway spruce trees in relation to
      accumulated chilling and forcing temperatures.
AB  - The timing of budburst of temperate trees is known to be controlled by
      complicated interactions of temperature and photoperiod. To improve the
      phenological models of budburst, better knowledge of the internal bud development
      preceding budburst in relation to environmental cues is needed. We studied the
      effect of accumulated chilling and forcing temperatures on the internal
      development of vegetative buds preceding budburst in Norway spruce [Picea abies
      (L.) Karst.]. Branches from 17-year-old trees of southern Finnish origin were
      transferred eight times at 1- to 2-week intervals from October to December 2007
      from the field at Punkaharju (61 degrees 48'N, 29 degrees 20'E) to the greenhouse
      with forcing conditions (day length 12 h, +20  degrees C). After seven different
      durations of forcing, the developmental phase and primordial shoot growth of the
      buds were analysed at the stereomicroscopic level. Air temperature was recorded
      hourly throughout the study period. The accumulated chilling unit sum had a
      significant effect on the temperature sum that was required to attain a certain
      developmental phase; a higher amount of chilling required a lower amount of
      forcing. The variation in the rate of development of different buds within each
      sample branch in relation to the chilling unit and forcing temperature sum was
      low. Regarding primordial shoot growth, there was also an inverse relation
      between accumulated chilling and forcing, i.e., a higher accumulated chilling
      unit sum before forcing required a lower temperature sum to initiate primordial
      shoot growth and resulted in a stronger effect of accumulated forcing. A second
      order regression model with an interaction of chilling and forcing explained the
      variation of primordial shoot growth with high precision (R(2) = 0.88). However,
      further studies are required to determine the final parameter values to be used
      in phenological modelling.

PMID- 24876294
TI  - Vertical variations in wood CO2 efflux for live emergent trees in a Bornean
      tropical rainforest.
AB  - Difficult access to 40-m-tall emergent trees in tropical rainforests has resulted
      in a lack of data related to vertical variations in wood CO2 efflux, even though
      significant variations in wood CO2 efflux are an important source of errors when
      estimating whole-tree total wood CO2 efflux. This study aimed to clarify vertical
      variations in wood CO2 efflux for emergent trees and to document the impact of
      the variations on the whole-tree estimates of stem and branch CO2 efflux. First,
      we measured wood CO2 efflux and factors related to tree morphology and
      environment for seven live emergent trees of two dipterocarp species at four to
      seven heights of up to ~ 40 m for each tree using ladders and a crane. No
      systematic tendencies in vertical variations were observed for all the trees.
      Wood CO2 efflux was not affected by stem and air temperature, stem diameter, stem
      height or stem growth. The ratios of wood CO2 efflux at the treetop to that at
      breast height were larger in emergent trees with relatively smaller diameters at
      breast height. Second, we compared whole-tree stem CO2 efflux estimates using
      vertical measurements with those based on solely breast height measurements. We
      found similar whole-tree stem CO2 efflux estimates regardless of the patterns of
      vertical variations in CO2 efflux because the surface area in the canopy, where
      wood CO2 efflux often differed from that at breast height, was very small
      compared with that at low stem heights, resulting in little effect of the
      vertical variations on the estimate. Additionally, whole-tree branch CO2 efflux
      estimates using measured wood CO2 efflux in the canopy were considerably
      different from those measured using only breast height measurements.
      Uncertainties in wood CO2 efflux in the canopy did not cause any bias in stem CO2
      efflux scaling, but affected branch CO2 efflux.

PMID- 24876295
TI  - Phenological niches and the future of invaded ecosystems with climate change.
AB  - In recent years, research in invasion biology has focused increasing attention on
      understanding the role of phenology in shaping plant invasions. Multiple studies
      have found non-native species that tend to flower distinctly early or late in the
      growing season, advance more with warming or have shifted earlier with climate
      change compared with native species. This growing body of literature has focused
      on patterns of phenological differences, but there is a need now for mechanistic
      studies of how phenology contributes to invasions. To do this, however, requires
      understanding how phenology fits within complex functional trait relationships.
      Towards this goal, we review recent literature linking phenology with other
      functional traits, and discuss the role of phenology in mediating how plants
      experience disturbance and stress-via climate, herbivory and competition-across
      the growing season. Because climate change may alter the timing and severity of
      stress and disturbance in many systems, it could provide novel opportunities for
      invasion-depending upon the dominant climate controller of the system, the
      projected climate change, and the traits of native and non-native species. Based
      on our current understanding of plant phenological and growth strategies
      especially rapid growing, early-flowering species versus later-flowering species
      that make slower-return investments in growth-we project optimal periods for
      invasions across three distinct systems under current climate change scenarios.
      Research on plant invasions and phenology within this predictive framework would
      provide a more rigorous test of what drives invader success, while at the same
      time testing basic plant ecological theory. Additionally, extensions could
      provide the basis to model how ecosystem processes may shift in the future with
      continued climate change. 

PMID- 24876296
TI  - Bulk elastic moduli and solute potentials in leaves of freshwater, coastal and
      marine hydrophytes. Are marine plants more rigid?
AB  - Bulk modulus of elasticity (E), depicting the flexibility of plant tissues, is
      recognized as an important component in maintaining internal water balance.
      Elevated E and comparatively low osmotic potential (Psipi) may work in concert to
      effectively maintain vital cellular water content. This concept, termed the 'cell
      water conservation hypothesis', may foster tolerance for lower soil-water
      potentials in plants while minimizing cell dehydration and shrinkage. Therefore,
      the accumulation of solutes in marine plants, causing decreases in Psipi, play an
      important role in plant-water relations and likely works with higher E to achieve
      favourable cell volumes. While it is generally held that plants residing in
      marine systems have higher leaf tissue E, to our knowledge no study has
      specifically addressed this notion in aquatic and wetland plants residing in
      marine and freshwater systems. Therefore, we compared E and Psipi in leaf tissues
      of 38 freshwater, coastal and marine plant species using data collected in our
      laboratory, with additional values from the literature. Overall, 8 of the 10
      highest E values were observed in marine plants, and 20 of the lowest 25 E values
      were recorded in freshwater plants. As expected, marine plants often had lower
      Psipi, wherein the majority of marine plants were below -1.0 MPa and the majority
      of freshwater plants were above -1.0 MPa. While there were no differences among
      habitat type and symplastic water content (thetasym), we did observe higher
      thetasym in shrubs when compared with graminoids, and believe that the
      comparatively low thetasym observed in aquatic grasses may be attributed to their
      tendency to develop aerenchyma that hold apoplastic water. These results, with
      few exceptions, support the premise that leaf tissues of plants acclimated to
      marine environments tend to have higher E and lower Psipi, and agree with the
      general tenets of the cell water conservation hypothesis. 

PMID- 24876297
TI  - Molecular basis of floral petaloidy: insights from androecia of Canna indica.
AB  - Floral organs that take on the characteristics of petals can occur in all whorls
      of the monocot order Zingiberales. In Canna indica, the most ornamental or
      'petaloid' parts of the flowers are of androecial origin and are considered
      staminodes. However, the precise nature of these petaloid organs is yet to be
      determined. In order to gain a better understanding of the genetic basis of
      androecial identity, a molecular investigation of B- and C-class genes was
      carried out. Two MADS-box genes GLOBOSA (GLO) and AGAMOUS (AG) were isolated from
      young inflorescences of C. indica by 3' rapid amplification of cDNA ends
      polymerase chain reaction (3'-RACE PCR). Sequence characterization and
      phylogenetic analyses show that CiGLO and CiAG belong to the B- and C-class MADS
      box gene family, respectively. CiAG is expressed in petaloid staminodes, the
      labellum, the fertile stamen and carpels. CiGLO is expressed in petals, petaloid
      staminodes, the labellum, the fertile stamen and carpels. Expression patterns in
      mature tissues of CiGLO and CiAG suggest that petaloid staminodes and the
      labellum are of androecial identity, in agreement with their position within the
      flower and with described Arabidopsis thaliana expression patterns. Although B-
      and C-class genes are important components of androecial determination, their
      expression patterns are not sufficient to explain the distinct morphology
      observed in staminodes and the fertile stamen in C. indica. 

PMID- 24876298
TI  - Learning from nature: the use of non-model species to identify novel acclimations
      to flooding stress.
AB  - Excess water in the form of waterlogged soil or deeper submergence (generically
      termed 'flooding') influences plant growth, survival and species distribution in
      many natural ecosystems. It also has a negative impact on crop growth and yield
      since many agricultural species are flooding intolerant. The often devastating
      effect of flooding on plant performance is related to its interference with gas
      exchange between the plant and its environment. This results in energy deficiency
      and carbohydrate starvation. In the near future, flooding frequency is expected
      to increase due to global climate change and the human population is expected to
      increase to ~9 billion people by 2050. The need for increased agricultural
      productivity is self-evident and this will require a better mechanistic
      understanding of the interaction between plants and abiotic stresses such as
      flooding. We argue that, in seeking this understanding, we should not restrict
      the research to model species such as rice (Oryza sativa) and Arabidopsis
      (Arabidopsis thaliana). This is because some stress-tolerance mechanisms are not
      found in these species. Examples are given of how flooding tolerance is achieved
      by non-model species of Rumex and Rorippa that have evolved to cope with flooding
      in natural environments. These findings will add usefully to the spread of
      resources available to plant breeding programmes aimed at improving flooding
      tolerance in crop plants. 

PMID- 24876299
TI  - Waterlogging-induced changes in root architecture of germplasm accessions of the
      tropical forage grass Brachiaria humidicola.
AB  - Waterlogging is one of the major factors limiting the productivity of pastures in
      the humid tropics. Brachiaria humidicola is a forage grass commonly used in zones
      prone to temporary waterlogging. Brachiaria humidicola accessions adapt to
      waterlogging by increasing aerenchyma in nodal roots above constitutive levels to
      improve oxygenation of root tissues. In some accessions, waterlogging reduces the
      number of lateral roots developed from main root axes. Waterlogging-induced
      reduction of lateral roots could be of adaptive value as lateral roots consume
      oxygen supplied from above ground via their parent root. However, a reduction in
      lateral root development could also be detrimental by decreasing the surface area
      for nutrient and water absorption. To examine the impact of waterlogging on
      lateral root development, an outdoor study was conducted to test differences in
      vertical root distribution (in terms of dry mass and length) and the proportion
      of lateral roots to the total root system (sum of nodal and lateral roots) down
      the soil profile under drained or waterlogged soil conditions. Plant material
      consisted of 12 B. humidicola accessions from the gene bank of the International
      Center for Tropical Agriculture, Colombia. Rooting depth was restricted by 21
      days of waterlogging and confined to the first 30 cm below the soil surface.
      Although waterlogging reduced the overall proportion of lateral roots, its
      proportion significantly increased in the top 10 cm of the soil. This suggests
      that soil flooding increases lateral root proliferation of B. humidicola in the
      upper soil layers. This may compensate for the reduction of root surface area
      brought about by the restriction of root growth at depths below 30 cm. Further
      work is needed to test the relative efficiency of nodal and lateral roots for
      nutrient and water uptake under waterlogged soil conditions. 

PMID- 24876300
TI  - Poplar saplings exposed to recurring temperature shifts of different amplitude
      exhibit differences in leaf gas exchange and growth despite equal mean
      temperature.
AB  - Most investigations of plant responses to changes in temperature have focused on
      a constant increase in mean day/night temperature without considering how
      differences in temperature cycles can affect physiological processes and growth.
      To test the effects of changes in growth temperature on foliar carbon balance and
      plant growth, we repeatedly exposed poplar saplings (Populus deltoides * nigra)
      to temperature cycles consisting of 5 days of a moderate (M, +5  degrees C) or
      extreme (E, +10  degrees C) increase in temperature followed by 5 days of a
      moderate (M, -5  degrees C) or extreme (E, -10  degrees C) decrease in
      temperature, with respect to a control treatment (C, 23.4  degrees C). The
      temperature treatments had the same mean temperature over each warm and cool
      cycle and over the entire study. Our goal was to examine the influence of
      recurring temperature shifts on growth. Net photosynthesis (A) was relatively
      insensitive to changes in growth temperature (from 20 to 35  degrees C),
      suggesting a broad range of optimum temperature for photosynthesis. Leaf
      respiration (R) exhibited substantial acclimation to temperature, having nearly
      the same rate at 13  degrees C as at 33  degrees C. There was no evidence that
      preconditioning through temperature cycles affected the response of A or R to
      treatment temperature fluctuations. Averaged across the complete warm/cool
      temperature cycle, the A : R ratio did not differ among the temperature
      treatments. While foliar carbon balance was not affected, the temperature
      treatments significantly affected growth. Whole-plant biomass was 1.5 times
      greater in the M treatment relative to the C treatment. Carbon allocation was
      also affected with shoot volume and biomass greater in the M and E treatments
      than in the C treatment. Our findings indicate that temperature fluctuations can
      have important effects on growth, though there were few effects on leaf gas
      exchange, and can help explain differences in growth that are not correlated with
      mean growth temperature. 

PMID- 24876301
TI  - Biaxial tensile tests identify epidermis and hypodermis as the main structural
      elements of sweet cherry skin.
AB  - The skin of developing soft and fleshy fruit is subjected to considerable growth
      stress, and failure of the skin is associated with impaired barrier properties in
      water transport and pathogen defence. The objectives were to establish a
      standardized, biaxial tensile test of the skin of soft and fleshy fruit and to
      use it to characterize and quantify mechanical properties of the sweet cherry
      (Prunus avium) fruit skin as a model. A segment of the exocarp (ES) comprising
      cuticle, epidermis, hypodermis and adhering flesh was mounted in the elastometer
      such that the in vivo strain was maintained. The ES was pressurized from the
      inner surface and the pressure and extent of associated bulging were recorded.
      Pressure : strain responses were almost linear up to the point of fracture,
      indicating that the modulus of elasticity was nearly constant. Abrading the
      cuticle decreased the fracture strain but had no effect on the fracture pressure.
      When pressure was held constant, bulging of the ES continued to increase. Strain
      relaxation upon releasing the pressure was complete and depended on time. Strains
      in longitudinal and latitudinal directions on the bulging ES did not differ
      significantly. Exocarp segments that released their in vivo strain before the
      test had higher fracture strains and lower moduli of elasticity. The results
      demonstrate that the cherry skin is isotropic in the tangential plane and
      exhibits elastic and viscoelastic behaviour. The epidermis and hypodermis, but
      not the cuticle, represent the structural 'backbone' in a cherry skin. This test
      is useful in quantifying the mechanical properties of soft and fleshy fruit of a
      range of species under standardized conditions. 

PMID- 24876303
TI  - Adherence in childhood asthma: the elephant in the room.
AB  - Adherence to inhaled steroids is suboptimal in many children with asthma and can
      lead to poor disease control. Many previous studies in paediatric populations
      have used subjective and inaccurate adherence measurements, reducing their
      validity. Adherence studies now often use objective electronic monitoring, which
      can give us an accurate indication of the extent of non-adherence in children
      with asthma. A review of the studies using electronic adherence monitoring shows
      that half of them report mean adherence rates of 50% or below, and the majority
      report rates below 75%. Reasons for non-adherence are both intentional and non
      intentional, incorporating illness perceptions, medication beliefs and practical
      adherence barriers. Interventions to improve adherence in the paediatric
      population have had limited success, with the most effective containing both
      educational and behavioural aspects.

PMID- 24876302
TI  - Is continuous positive airway pressure a feasible treatment modality for neonates
      with respiratory distress syndrome in a rural district hospital?
AB  - OBJECTIVES: To assess the feasibility of using nasal continuous positive airway
      pressure (nCPAP) in neonates with respiratory distress syndrome at district
      hospital level by assessing in-hospital survival rates and the impact on transfer
      rates. METHODS: A prospective database was kept from 2008 to record the outcomes
      of neonates with mild to moderate respiratory distress treated with nCPAP at a
      South African rural district hospital. Transfer rates were compared for the two
      years before and after introduction of neonatal nCPAP using additional
      retrospective data from the Perinatal Problem Identification Programme (PPIP) for
      comparison. Outcomes for nCPAP neonates for the first 5 years after programme
      implementation are presented. RESULTS: One hundred and twenty-eight babies were
      treated with nCPAP over the study period. Nine of 13 extremely low birth weight
      (<1000 g) babies died. Eighty-four (72.4%) of the babies weighing >1000 g were
      successfully treated, 16 (13.8%) were transferred after trial of nCPAP and 15
      (12.9%) died in hospital. Most of the transferred babies and deaths had co
      morbidities. There was a significant reduction in transfer rates of low birth
      weight babies from 21 to 7% in the first 2 years following the introduction of
      nCPAP. CONCLUSIONS: nCPAP for neonatal respiratory distress at the district
      hospital is feasible, safe and offers the potential for significant cost savings.

PMID- 24876304
TI  - Genome-wide association studies of refractive error and myopia, lessons learned,
      and implications for the future.
AB  - The investigation of the genetic basis of refractive error and myopia entered a
      new stage with the introduction of genome-wide association studies (GWAS).
      Multiple GWAS on many ethnic groups have been published over the years, providing
      new insight into the genetic architecture and pathophysiology of refractive
      error. This is a review of the GWAS published to date, the main lessons learned,
      and future possible directions of genetic studies of myopia and refractive error.

PMID- 24876305
TI  - Role of sialic acids in feline enteric coronavirus infections.
AB  - To initiate infections, many coronaviruses use sialic acids, either as receptor
      determinants or as attachment factors helping the virus find its receptor
      underneath the heavily glycosylated mucus layer. In the present study, the role
      of sialic acids in serotype I feline enteric coronavirus (FECV) infections was
      studied in feline intestinal epithelial cell cultures. Treatment of cells with
      neuraminidase (NA) enhanced infection efficiency, showing that terminal sialic
      acid residues on the cell surface were not receptor determinants and even
      hampered efficient virus-receptor engagement. Knowing that NA treatment of
      coronaviruses can unmask viral sialic acid binding activity, replication of
      untreated and NA-treated viruses was compared, showing that NA treatment of the
      virus enhanced infectivity in untreated cells, but was detrimental in NA-treated
      cells. By using sialylated compounds as competitive inhibitors, it was
      demonstrated that sialyllactose (2,6-alpha-linked over 2,3-alpha-linked) notably
      reduced infectivity of NA-treated viruses, whereas bovine submaxillary mucin
      inhibited both treated and untreated viruses. In desialylated cells, however,
      viruses were less prone to competitive inhibition with sialylated compounds. In
      conclusion, this study demonstrated that FECV had a sialic acid binding capacity,
      which was partially masked by virus-associated sialic acids, and that attachment
      to sialylated compounds could facilitate enterocyte infections. However, sialic
      acid binding was not a prerequisite for the initiation of infection and virus
      receptor engagement was even more efficient after desialylation of cells,
      indicating that FECV requires sialidases for efficient enterocyte infections. 

PMID- 24876306
TI  - miRNA modulation of SOCS1 using an influenza A virus delivery system.
AB  - Difficulties associated with efficient delivery and targeting of miRNAs to cells
      is hampering the real world application of miRNA technology. This study utilized
      an influenza A-based delivery system to express miR-155 in order to knockdown
      SOCS1 mRNA. Using qPCR and dual luciferase technology we show that miR-155
      delivery resulted in a significant increase in cellular miR-155 which facilitated
      a downregulation of SOCS1 gene expression and a functional increase in IL-6 and
      IFN-beta cytokines.

PMID- 24876307
TI  - Role of peroxidation and heme catalysis in coloration of raw meat.
AB  - It is known, that lipid peroxidation is one of the main factors limiting the
      quality and acceptability of meat and other animal tissues. The current data
      concerning connection of heme and peroxidation were summarized and analysed here.
      The muscle food compounds that are most influenced by oxidative processes include
      unsaturated fatty acids of lipids, amino acids of proteins and heme groups of
      pigments. Heme proteins and particularly myoglobin are abundant in muscle
      tissues. Meat colour is primarily influenced by the concentration and chemical
      State of heme pigments, myoglobin and hemoglobin. Oxygenated myoglobin oxidized
      to the brown metmyoglobin form and its accumulation is highly correlated with
      progress of lipid peroxidation. Heme proteins such as hemoglobin or myoglobin
      accelerate the decomposition of hydroperoxides to free radicals. Metmyoglobin
      possesses "pseudoperoxidase" activity and catalyzes the oxidation of various
      compounds following the reaction with hydrogen peroxide. The reaction between
      hydrogen peroxide and metmyoglobin results in the formation of two active
      hypervalent myoglobin species, perferrylmyoglobin (.MbFe(IV)=0) and
      ferrylmyoglobin (MbFe(IV)=0), which participate in lipid oxidation catalysis.
      Both MbFe(IV)=0 and .MbFe(IV)=0 are deactivated in the presence of reducing
      agents, whose nature determines the overall effect of the pseudoperoxidase cycle.
      Hypothesis can be put forward that loss of cellular antioxidants might precede
      the rise of peroxidase-like activity, thus being a sign of incipient
      discoloration of meats and muscle components of foods.

PMID- 24876308
TI  - Drying method effects on the antioxidant activity of quince (Cydonia oblonga
      Miller) tea.
AB  - BACKGROUND: Quince has many health benefits. Dried quince has been used as a tea
      for centuries. The aim of this study was to investigate the influences of two
      drying methods on the antioxidant activity of the quince. MATERIAL AND METHODS:
      Fifty two fresh Iranian quinces (Cydonia oblonga) were obtained from different
      parts of Shiraz. Half of the quinces were peeled and both peel and flesh
      immediately frozen at -20 degrees C individually. The remainder was divided in
      two groups, and dried with sun and oven drying methods. Proximate analysis,
      caloric, mineral and vitamin C contents were determined in the fresh quinces. The
      total phenolic, DPPH radical scavenging activity and reducing power analysis were
      done on flesh, peel, sun-dried and oven-dried quinces. RESULTS: The proximate and
      nutritional composition of the fresh quinces was similar to those reported by
      other researchers. Oven-dried and quince peel contained higher amounts of
      phenolics than the sun-dried and flesh quinces, respectively. Sun-dried and flesh
      samples showed lower radical scavenging effect and reducing antioxidant capacity
      than oven-dried and quince peel, respectively. CONCLUSION: Overall, oven drying
      can better preserve the antioxidative activity of the quince.

PMID- 24876309
TI  - Effect of ethanolic flax (Linum usitatissimum L.) extracts on lipid oxidation and
      changes in nutritive value of frozen-stored meat products.
AB  - BACKGROUND: Flaxseed (Linum usitatissimum L.) is an important source of phenolic
      compounds, mainly lignans. Antioxidant capacities of flaxseed extracts that
      contain the compounds have been reported earlier. However, there is a lack of
      accessible information about their activity against lipid oxidation in meat
      products. Therefore, the effect of ethanolic flaxseed extracts (EFEs) on lipid
      stability and changes in nutritive value of frozen-stored meat products (pork
      meatballs and burgers) was determined. MATERIAL AND METHODS: EFEs from three
      Polish flax varieties (Szafir, Oliwin, Jantarol) were applied in the study.
      During 150-day storage of meat products, the lipid oxidation (peroxide and TBARS
      value) and thiamine retention were periodically monitored, alongside with
      methionine and lysine availability and protein digestibility. RESULTS: The
      addition of EFEs significantly limited lipid oxidation in stored meatballs and
      burgers. EFE from brown seeds of Szafir var. was superior to the others from
      golden seeds of Jantarol and Oliwin. Moreover, the extracts reduced changes in
      thiamine and available lysine content, as well as protein digestibility, during
      storage time. The effect of EFE addition on available methionine retention was
      limited. CONCLUSION: The ethanolic flaxseed extracts exhibit antioxidant activity
      during frozen storage of meat products. They can be utilized to prolong shelf
      life of the products by protecting them against lipid oxidation and deterioration
      of their nutritional quality. However, antioxidant efficiency of the extracts
      seems to depend on chemical composition of raw material (flax variety). Further
      investigations should be carried on to explain the issue.

PMID- 24876310
TI  - Optimization of extraction conditions of some polyphenolic compounds from parsley
      leaves (Petroselinum crispum).
AB  - BACKGROUND: Parsley leaf is a rich source of natural antioxidants, which serve a
      lot of functions in human body and prevent food from oxidation processes. The aim
      of the study was to investigate the influence of different extraction solvents
      and times of extraction on natural antioxidants content. Owing to the knowledge
      of the properties of extracted components and solvents, as well as their
      interactions, it is possible to achieve a high effectiveness of active compounds
      recovery. MATERIAL AND METHODS: Three different extraction solvents (acetone 70%
      in water, methanol 80% in water and distilled water) and different times of
      extraction (30 and 60 minutes) were used to determine the efficiency of
      extraction of polyphenols and catechins, antioxidant activity against free
      radicals DPPH and ABTS and the ability to chelate ion Fe(2+) in dried parsley
      leaves. Other natural antioxidants contents in parsley leaves were also
      determined. RESULTS AND DISCUSSION: In this study the best extraction solvent for
      polyphenols was acetone 70% and for catechins was distilled water. All extracts
      examined displayed the antioxidative activity, but water was the best solvent in
      the method of assaying the activity against ABTS(*+) and Fe(2+) ions chelating
      capability, whereas methanol turned out to be the least effective in this
      respect. Opposite results were observed in the case of determining the activity
      against DPPH(*). The prolongation of the extraction time enhanced or decreased
      antiradical activity in some cases. Additionally, important biologically active
      compounds in parsley leaves, such as vitamin C (248.31 mg/100 g dry matter),
      carotenoids (31.28 mg/100 g dry matter), chlorophyll (0.185 mg/g dry matter) were
      also analysed.

PMID- 24876311
TI  - Optimized microwave-assisted extraction of 6-gingerol from Zingiber officinale
      Roscoeand evaluation of antioxidant activity in vitro.
AB  - BACKGROUND: 6-Gingerol is one of the most pharmacologically active and abundant
      components in ginger, which has a wide array of biochemical and pharmacologic
      activities. In recent years, the application of microwave-assisted extraction
      (MAE) for obtaining bioactive compounds from plant materials has shown tremendous
      research interest and potential. In this study, an efficient microwave-assisted
      extraction (MAE) technique was developed to extract 6-gingerol from ginger. The
      extraction efficiency of MAE was also compared with conventional extraction
      techniques. MATERIAL AND METHODS: Fresh gingers (Zingiber officinale Rose.) were
      harvested at commercial maturity (originally from Shandong, laiwu, China). In
      single-factor experiments for the recovery of 6-gingerol, proper ranges of ratio
      of liquid to solid, ethanol proportion, microwave power, extraction time were
      determined. Based on the values obtained in single-factor experiments, a Box
      Behnken design (BBD) was applied to determine the best combination of extraction
      variables on the yield of 6-gingerol. RESULTS: The optimum extraction conditions
      were as follows: microwave power 528 W, ratio of liquid to solid 26 mL.g(-1),
      extraction time 31 s and ethanol proportion 78%. Furthermore, more 6-gingerol and
      total polyphenols contents were extracted by MAE than conventional methods
      including Maceration (MAC), Stirring Extraction (SE), Heat reflux extraction
      (HRE), Ultrasound-assisted extraction (UAE), as well as the antioxidant capacity.
      CONCLUSION: Microwave-assisted extraction showed obvious advantages in terms of
      high extraction efficiency and antioxidant activity of extract within shortest
      extraction time. Scanning electron microscopy (SEM) images of ginger powder
      materials after different extractions were obtained to provide visual evidence of
      the disruption effect. To our best knowledge, this is the first report about
      usage of MAE of 6-gingerol extraction from ginger, which could be referenced for
      the extraction of other active compounds from herbal plants.

PMID- 24876312
TI  - Biochemical and nutritional components of selected honey samples.
AB  - BACKGROUND: The purpose of this study was to investigate the relationship of
      biochemical (enzymes) and nutritional components in the selected honey samples
      from Malaysia. The relationship is important to estimate the quality of honey
      based on the concentration of these nutritious components. Such a study is
      limited for honey samples from tropical countries with heavy rainfall throughout
      the year. METHODOLOGY: A number of six honey samples that commonly consumed by
      local people were collected for the study. Both the biochemical and nutritional
      components were analysed by using standard methods from Association of Official
      Analytical Chemists (AOAC). Individual monosaccharides, disaccharides and 17
      amino acids in honey were determined by using liquid chromatographic method.
      RESULTS: The results showed that the peroxide activity was positively correlated
      with moisture content (r = 0.8264), but negatively correlated with carbohydrate
      content (r = 0.7755) in honey. The chromatographic sugar and free amino acid
      profiles showed that the honey samples could be clustered based on the type and
      maturity of honey. Proline explained for 64.9% of the total variance in principle
      component analysis (PCA). CONCLUSION: The correlation between honey components
      and honey quality has been established for the selected honey samples based on
      their biochemical and nutritional concentrations. PCA results revealed that the
      ratio of sucrose to maltose could be used to measure honey maturity, whereas
      proline was the marker compound used to distinguish honey either as floral or
      honeydew.

PMID- 24876313
TI  - Proteomic analysis of albumin and globulin fractions of pea (Pisum sativum L.)
      seeds.
AB  - BACKGROUND: Proteomic analysis is emerging as a highly useful tool in food
      research, including studies of food allergies. Two-dimensional gel
      electrophoresis involving isoelectric focusing and sodium dodecyl sulfate
      polyacrylamide gel electrophoresis is the most effective method of separating
      hundreds or even thousands of proteins. In this study, albumin and globulin
      tractions of pea seeds cv. Ramrod were subjected to proteomic analysis. Selected
      potentially alergenic proteins were identified based on their molecular weights
      and isoelectric points. MATERIAL AND METHODS: Pea seeds (Pisum sativum L.) cv.
      Ramrod harvested over a period of two years (Plant Breeding Station in Piaski
      Szelejewo) were used in the experiment. The isolated albumins, globulins and
      legumin and vicilin fractions of globulins were separated by two-dimensional gel
      electrophoresis. Proteomic images were analysed in the ImageMaster 2D Platinum
      program with the use of algorithms from the Melanie application. The relative
      content, isoelectric points and molecular weights were computed for all
      identified proteins. Electrophoregrams were analysed by matching spot positions
      from three independent replications. RESULTS: The proteomes of albumins,
      globulins and legumin and vicilin fractions of globulins produced up to several
      hundred spots (proteins). Spots most characteristic of a given fraction were
      identified by computer analysis and spot matching. The albumin proteome
      accumulated spots of relatively high intensity over a broad range of pi values of
      ~4.2-8.1 in 3 molecular weight (MW) ranges: I - high molecular-weight albumins
      with MW of ~50-110 kDa, II - average molecular-weight albumins with MW of ~20-35
      kDa, and III - low molecular-weight albumins with MW of ~13-17 kDa. 2D gel
      electrophoregrams revealed the presence of 81 characteristic spots, including 24
      characteristic of legumin and 14 - of vicilin. CONCLUSIONS: Two-dimensional gel
      electrophoresis proved to be a useful tool for identifying pea proteins. Patterns
      of spots with similar isoelectric points and different molecular weights or spots
      with different isoelectric points and similar molecular weights play an important
      role in proteome analysis. The regions characteristic of albumin, globulin and
      legumin and vicilin fractions of globulin with typical MW and pi values were
      identified as the results of performed 2D electrophoretic separations of pea
      proteins. 2D gel electrophoresis of albumins and the vicilin fraction of
      globulins revealed the presence of 4 and 2 spots, respectively, representing
      potentially allergenic proteins. They probably corresponded to vicilin fragments
      synthesized during post-translational modification of the analysed protein.

PMID- 24876314
TI  - Health effects of dietary fiber.
AB  - Dietary fibre is a group of food components which is resistant to digestive
      enzymes and found mainly in cereals, fruits and vegetables. Dietary fi ber and
      whole grains contain a unique blend of bioactive components including resistant
      starches, vitamins, minerals, phytochemicals and antioxidants. Dietary fi ber
      which indigestible in human small intestinal, on the other hand digested
      completely or partially fermented in the large intestine, is examined in two
      groups: water-soluble and water insoluble organic compounds. Dietary fi ber can
      be separated into many different fractions. These fractions include arabinoxylan,
      inulin, pectin, bran, cellulose, beta-glucan and resistant starch. Dietary fibres
      compose the major component of products with low energy value that have had an
      increasing importance in recent years. Dietary fibres also have technological and
      functional properties that can be used in the formulation of foods, as well as
      numerous beneficial effects on human health. Dietary fibre components organise
      functions of large intestine and have important physiological effects on glucose,
      lipid metabolism and mineral bioavailability. Today, dietary fibers are known to
      be protective effect against certain gastrointestinal diseases, constipation,
      hemorrhoids, colon cancer, gastroesophageal reflux disease, duodenal ulcer,
      diverticulitis, obesity, diabetes, stroke, hypertension and cardiovascular
      diseases. In this review the physicochemical and biological properties of dietary
      fibers and their important implications on human health will be investigated.

PMID- 24876315
TI  - Effects of physical activity during pregnancy and gestational weight gain on
      newborn weight and length at birth in Warminsko-Mazurskie province.
AB  - BACKGROUND: Epidemiological research has identified a relationship between
      maternal physical activity, early nutrition and infant birth weight with
      likelihood of developing future diseases. The aim of the study was to determine a
      relationship between gestational weight gain and physical activity during
      pregnancy to the nutritional status of newborns. MATERIAL AND METHODS: The
      presented study was conducted in the period from February 2010 until November
      2012 in the gynecological and obstetric clinics in Warminsko-Mazurskie
      voivodeship with various levels of reference. The research subjects included 510
      women in the puerperal period aged 18-36. The scope of the research included an
      assessment of the selected anthropometric parameters of both pregnant women (body
      mass, height, BMI, gestational weight gain) and newborns (infant birth weight,
      infant length, Ponderal Index), as well as an analysis of the connections between
      the gestational weight gain, physical activity during pregnancy and
      anthropometric parameters of newborns. RESULTS AND CONCLUSIONS: In the study
      group there was a significant percentage of women characterised by an inactive
      lifestyle and excessive gestational weight gain. There were significantly higher
      neonatal birth anthropometric parameters in women with abnormal excessive
      gestational weight gain than in women with normal and inappropriate - low
      gestational weight gain. The highest percentage of women with appropriate weight
      gain was observed in the group of women who are physically active, although this
      requires confirmation in larger population. Our studies have not shown
      statistically significant differences between the gestational weight gain and
      nutritional status of newborns in relation to the level of physical activity of
      pregnant women.

PMID- 24876316
TI  - Assessment of the risk of exposure to cadmium and lead as a result of the
      consumption of low-fat dairy products by expectant and lactating women.
AB  - BACKGROUND: The study aimed to assess the risk related to consumption of low-fat
      dairy products by expectant and lactating women. MATERIAL AND METHODS: A survey
      was used to verify the popularity of such products among expectant and lactating
      women and then the content of Cd and Pb in low-fat dairy products was determined.
      RESULTS: In the group of expectant women consuming dairy products, nearly 93% of
      the respondents consumed low-fat dairy products, while among lactating women the
      result was 90%. Both the expectant and lactating women mostly preferred milk and
      fruit yoghurt. It was found that the studied low-fat products did not contain
      more Cd and Pb than their standard counterparts. CONCLUSION: Taking into account
      the intake of low-fat milk and dairy products declared by respondents, such
      products must be regarded safe in terms of Cd and Pb content. The maximum supply
      of Cd and Pb for both groups of women did not exceed 3% TWI and 2% BMDL10.

PMID- 24876317
TI  - Primary spindle cell sarcoma of the breast masquerading as necrotizing fasciitis.
AB  - Breast sarcomas are rare neoplasms arising from the few epithelial elements of
      the gland. It represents much <1% of all breast cancer. Of the heterogeneous
      group of sarcomas, the more common subtypes include spindle cell sarcoma. The
      main risk factor for the development of breast sarcomas is previous radiation
      therapy following breast-conservation surgery for breast cancer or non-Hodgkin's
      lymphoma. We report on an idiopathic presentation of spindle cell sarcoma in an
      otherwise healthy middle-aged woman. An emphasis is made on the rare occurrence
      of lymphatic metastasis. We discuss our recommended management strategy with
      particular reference to the benefit of multidisciplinary team decision-making. 

PMID- 24876318
TI  - Mucinous adenocarcinoma of the umbilicus 8 years following anterior resection for
      villous adenoma of the rectum.
AB  - We present the case of an 80-year-old retired consultant histopathologist who
      presented to us with a malignant umbilical mass 8years following resection of a
      sigmoid adenoma. The report details initial investigation and management of the
      umbilical mass and the subsequently discovered pelvic recurrence. Our conclusions
      of its origin, as a malignant transformation due to seeding of the original
      sigmoid adenoma, show the slow progression of some colorectal tumours; and the
      importance of obtaining a complete specimen intra-operatively. 

PMID- 24876319
TI  - Laparoscopic reconstruction of the extrahepatic bile duct using a jejunal tube:
      an innovative, more physiological and anatomical technique for biliodigestive
      derivation?.
AB  - The incidence of bile duct injuries has increased as a consequence of the
      increasing number of cholecystectomies. However, the results of biliodigestive
      derivation currently used for bile duct reconstruction are unsatisfactory. We
      report here the case of a patient with iatrogenic Bismuth II bile duct injury and
      propose a new technique that permits more anatomical and physiological
      reconstruction of extensive bile duct injuries using transverse retubularization
      of a pedicled jejunal segment interposed between the bile duct and duodenum. 

PMID- 24876320
TI  - Internal hernia and small bowel obstruction caused by a linear cutter staple at
      appendiceal stump following laparoscopic appendectomy.
AB  - Commonly linear staplers are used to perform laparoscopic appendectomies. We
      report a case of a small bowel obstruction caused by a staple on the appendiceal
      stump creating an internal hernia <1 week after laparoscopic appendectomy. We
      discuss the available literature on bowel obstructions caused by staples. Most of
      the discussed complications were caused by staples free in the abdomen, which
      were remote from the staple line. Generally, loose staples do not cause problems,
      but if noted during the operation, we recommend removal to prevent future
      obstruction. 

PMID- 24876321
TI  - Synchronous asymptomatic colonic metastasis from primary esophageal squamous cell
      carcinoma.
AB  - The management of synchronous asymptomatic colonic metastases from primary
      esophageal squamous cell carcinoma (ESCC) has not yet been reported. A 64-year
      old male patient was diagnosed with middle thoracic ESCC. The patient received
      chemoradiotherapy and incomplete response/stable disease was achieved.
      Preoperative colonoscopy revealed a 1.0-cm submucosal tumor at the splenic
      flexure of the colon, and biopsy results indicated possible metastasis from
      primary ESCC. The patient underwent subtotal esophagectomy and the colonic tumor
      was excised. A postoperative pathological diagnosis confirmed that the colonic
      tumor had metastasized from primary ESCC. Even though the patient was discharged
      18 days after surgery without any complications, he died on the 72nd
      postoperative day due to multiple bone metastases and pleural dissemination. Our
      findings suggest that even with well-controlled and asymptomatic colonic
      metastasis from primary esophageal lesions, the prognosis of patients with
      primary ESCC is poor. 

PMID- 24876322
TI  - Confirmed testicular torsion in a 67 year old.
AB  - Torsion amongst the elderly population is rarely described. This case presents
      the oldest surgically confirmed case of testicular torsion, in a 67-year-old
      male, within the UK. Presenting to the emergency department with a 10-day history
      of left-sided testicular pain, initially treated with antibiotics. There was no
      pyrexia or urinary symptoms and negative urine dipstick. In adults above the age
      of 40, likely diagnoses include epididymo-orchitis, epididymitis, neoplasm or
      hydrocele. Clinical differentiation with epididymo-orchitis can be difficult in
      any age range. Clinical signs such as fever, elevated C-reactive protein and
      positive urine dipstick test are suggestive of epididymo-orchitis/orchitis. This
      case study demonstrates that testicular torsion can occur at any age, and
      clinical suspicion should always be high in patients presenting with testicular
      pain and a negative urine dipstick, regardless of age. Although risk in this
      subgroup is low, the identification of a potentially reversible testicular
      abnormality should be of high priority. 

PMID- 24876323
TI  - Complexities of abdominoperineal surgery: synchronous resection of an ano-rectal
      adenocarcinoma and pelvic schwannoma.
AB  - Abdominoperineal resection (APR) is indicated for low rectal/ano-rectal cancers.
      It necessitates fastidious pelvic dissection posing certain operative
      difficulties. We present the surgical challenges in a unique case of a patient
      presenting with a low rectal adenocarcinoma and a synchronous pelvic schwannomas,
      both requiring resection. A 71-year-old gentleman presented for surveillance
      colonoscopy following previous excision of colonic polyps. This investigation
      revealed a polypoid mass at the ano-rectal junction which was histologically
      proven as an adenocarcinoma with high-grade dysplasia. A staging computed
      tomography scan revealed an incidental 10 * 15 cm homogeneous, pre-sacral mass.
      After meticulous operative planning, the patient underwent successful open
      resection of this mass and concurrent APR for his low rectal lesion. This case
      demonstrates a rare presentation of a low rectal adenocarcinoma and concurrent
      pelvic schwannoma. We discuss the technical difficulties encountered in the
      management of such complex pelvic tumours and highlight the successful outcomes
      of the synchronous resection. 

PMID- 24876324
TI  - Twenty-year-old female with leiomyosarcoma of the breast.
AB  - Primary leiomyosarcoma is a disease with <50 documented cases in the literature
      worldwide. The standard of care for these tumors has not been established.
      Physicians who have seen these cases in the past have used wide local excision
      with or without adjunctive chemo-radiation therapy. We review the literature
      concerning the mainstay of treatment as well as present a new case of an
      adolescent with primary leiomyosarcoma. 

PMID- 24876325
TI  - Laparoscopic resection of a retroperitoneal pelvic schwannoma.
AB  - Schwannomas are rarely located in the pelvis. A 54-year-old woman was found
      incidentally to have a tumor in the abdomen. Abdominal computed tomography and
      magnetic resonance imaging revealed a well-defined, heterogeneous tumor, 5 cm in
      diameter, in the pelvic cavity. With a diagnosis of a mesenteric tumor, a
      laparoscopic procedure was performed. Intra-operatively, an elastic tumor was
      identified in the pelvis adjacent to the right internal iliac vein and ureter.
      The tumor was dissected free from adjacent structures using Liga-Sure and blunt
      maneuvers. A complete laparoscopic excision was performed. Histopathological
      examination revealed a benign schwannoma. The patient had an uneventful post
      operative course, and was discharged on the fourth post-operative day.
      Laparoscopic treatment is useful and feasible for retroperitoneal pelvic
      schwannoma, with minimal invasiveness and an early post-operative recovery. Thus,
      this procedure may be the first-choice surgical procedure for retroperitoneal
      pelvic schwannomas. 

PMID- 24876326
TI  - A mystifying mass.
AB  - A 57-year-old male was referred by his general practitioner (GP) to hospital with
      right upper quadrant pain and a palpable mass (10 * 9 cm). He had been assessed
      by his GP several weeks earlier and represented as initial treatment failed. On
      his second presentation a mass was evident and thought to represent cholecystitis
      by the referring GP. However, the correct and prompt use of appropriate
      radiological imaging enabled swift diagnosis and management of atypical acute
      appendicitis through microbial specific therapy. Atypical appendicitis delays
      diagnosis and treatment which represents greater levels of appendiceal ischaemia
      and heightened perforation risk. This case study highlights the non-surgical
      management of acute atypical appendicitis and also reinforces the use of
      appropriate imaging modalities. 

PMID- 24876327
TI  - Postoperative radiotherapy in diffuse idiopathic skeletal hyperostosis:
      prophylaxis of recurrence after resection of osteophytes from C3 to C5 in a case
      of dysphagia.
AB  - In diffuse idiopathic skeletal hyperostosis (DISH), recurrence of hyperostosis
      after surgical removal is common. While both non-steroidal anti-inflammatory
      drugs (NSAIDs) and radiotherapy have been used in the prevention of heterotopic
      ossification, only NSAIDs have been applied for prophylaxis in DISH. As a
      previously undescribed prophylaxis of recurrence in DISH, we report a case
      treated with local radiotherapy. 

PMID- 24876328
TI  - Placental infarction probably associated with late term premature delivery.
AB  - Here the histopathology findings of placental infarction associated with late
      preterm birth are reported. The subject was a male neonate delivered at 34 weeks
      and 5 days of gestation with a birth weight of ~2500 g. His mother had been
      diagnosed with a threatened premature birth at 27 weeks of pregnancy. The size
      and weight of the placenta was considered appropriate for gestational age. On the
      cut surface of the placenta, a white-colored focal infarct was noted beneath the
      site of the umbilical cord insertion. There were small focal infarcts scattered
      within the marginal area. There were no particular vascular abnormalities or
      apparent thrombi. The placental villi were of appropriate maturity for the
      gestational age and the villous vessels showed no structural abnormalities. This
      case highlights the benefits of examining the histopathology of postpartum
      placentas for preterm children to explore their significance in premature birth. 

PMID- 24876329
TI  - Human papilloma virus-16 causing giant condyloma acuminata.
AB  - A 28-year-old multiparous lady presented to the Gynaecology outpatient department
      with a 12 * 5 cm warty growth in the vulva. A biopsy of the growth revealed
      condyloma acuminata of the vulva. Simple vulvectomy was done. A PCR of the
      specimen detected the presence of human papilloma virus (HPV)-16 which is usually
      considered as a high-risk HPV type for carcinogenesis. 

PMID- 24876330
TI  - Breast filariasis.
AB  - Filarial involvement of breast is a rare entity. Here is an unusual case of an
      old lady with right breast lump with axillary lymphadenopathy mimicking breast
      carcinoma, cytologically diagnosed as filarial mastitis. The patient subsequently
      received antihelmenthic therapy and showed marked clinical response within few
      weeks. 

PMID- 24876331
TI  - Metastatic breast cancer in the mandibular condyle mimicking temporomandibular
      joint (TMJ) disease.
AB  - Metastases or tumour to the jaws are rare and those to the temporomandibular
      joint (TMJ) are even rarer. The symptoms like preauricular pain, swelling and
      clicking are generally associated with TMJ disease. But the same symptoms are
      also found in tumours of the jaws or other diseases. We report on the case of a
      48-year-old woman with a 12-year history of breast cancer who was referred to our
      department for clarification of preauricular swelling and pain. The possible
      aetiology of TMJ disorders and the frequency and localization of metastases to
      the jaws are discussed. 

PMID- 24876332
TI  - Major complications following total en bloc spondylectomy for giant-cell tumor.
AB  - The authors present the case of a 32-year-old Caucasian female with a giant-cell
      tumor of the eighth thoracic vertebra, causing unremitting pain, segmental
      kyphosis and imminent local instability. A total en bloc spondylectomy by a
      posterior-only approach was performed, complemented with anterior-column
      reconstruction with a titanium mesh and structural allograft, as well as pedicle
      screw fixation. Despite the surgery being uneventful, several complications
      developed over the ensuing weeks: bilateral hemothorax, empyema and sepsis,
      requiring numerous revision surgeries for postoperative infection. The same
      pathogen was identified in different samples collected, including a sample from
      the allograft used. Only the aggressive therapeutic measures adopted allowed
      improvement in clinical and analytic parameters. The present report alerts to the
      possible complications following major spine surgery, and raises concerns on the
      safety of the bone allografts provided, renewing the interest in the development
      of alternative bone substitutes. 

PMID- 24876333
TI  - Intrathoracic migration of a Kirschner wire.
AB  - Kirschner (K) wires can easily migrate, resulting in serious complications. We
      report a 49-year-old woman who had a rare and late complication related to the
      migration of K wire. It had been used for left hip replacement 8 years ago. The
      patient admitted to our hospital with breathing-dependent chest pain and
      increasing dyspnea for ~2 h. Chest X-ray and chest computed tomographic scans
      revealed the presence of a metallic image of ~5-6 cm in the right hemithorax.
      There was a large hemothorax but no pneumothorax. A right thoracotomy was
      performed and the wire was removed without complications. Surprisingly, no injury
      was noted to any intervening abdominal structure intra-operatively. Patients, who
      are treated with K wire, should be informed of the risk of wire migration and
      should undergo regular postoperative follow-ups including radiography. 

PMID- 24876334
TI  - Component separation in abdominal trauma.
AB  - Component separation is established for complex hernia repairs. This case
      presents early component separation and release of the anterior and posterior
      sheath to facilitate closure of the abdominal wall following emergency
      laparotomy, reinforcing the repair with a biological mesh. On Day 11 following an
      emergency laparotomy for penetrating trauma, this patient underwent component
      separation and release of the anterior and posterior sheath. An intra-abdominal
      biological mesh was secured, and the fascia and skin closed successfully. Primary
      abdominal closure can be achieved in patients with penetrating abdominal trauma
      with the use of component separation and insertion of intra-abdominal biological
      mesh, where standard closure is not possible. 

PMID- 24876335
TI  - The Trotter procedure: a forgotten approach?
AB  - Anatomically, the surgical management of tongue base lesions is a challenging
      prospect for any head and neck surgeon. William Trotter described a median labio
      mandibular glossotomy for access to such lesions (Meis JM, Enzinger FM. Myolipoma
      of soft tissue. Am J Surg Pathol 1991;15:121-5). Not widely reported, this
      approach still remains an important tool in the armamentarium of head and neck
      surgeons. We outline the use of this approach to remove a myolipoma from the
      tongue base. 

PMID- 24876336
TI  - Advanced micro- and nanofabrication technologies for tissue engineering.

PMID- 24876337
TI  - Software for evaluation of EPR-dosimetry performance.
AB  - Electron paramagnetic resonance (EPR) with tooth enamel is a method extensively
      used for retrospective external dosimetry. Different research groups apply
      different equipment, sample preparation procedures and spectrum processing
      algorithms for EPR dosimetry. A uniform algorithm for description and comparison
      of performances was designed and implemented in a new computer code. The aim of
      the paper is to introduce the new software 'EPR-dosimetry performance'. The
      computer code is a user-friendly tool for providing a full description of method
      specific capabilities of EPR tooth dosimetry, from metrological characteristics
      to practical limitations in applications. The software designed for scientists
      and engineers has several applications, including support of method calibration
      by evaluation of calibration parameters, evaluation of critical value and
      detection limit for registration of radiation-induced signal amplitude,
      estimation of critical value and detection limit for dose evaluation, estimation
      of minimal detectable value for anthropogenic dose assessment and description of
      method uncertainty. 

PMID- 24876338
TI  - Evaluation of organ and effective doses during paediatric barium meal
      examinations using PCXMC 2.0 Monte Carlo code.
AB  - Radiation protection and estimation of the radiological risk in paediatric
      radiology is essential due to children's significant radiosensitivity and their
      greater overall health risk. The purpose of this study was to estimate the organ
      and effective doses of paediatric patients undergoing barium meal (BM)
      examinations and also to evaluate the assessment of radiation Risk of Exposure
      Induced cancer Death (REID) to paediatric patients undergoing BM examinations.
      During the BM studies, fluoroscopy and multiple radiographs are involved. Since
      direct measurements of the dose in each organ are very difficult if possible at
      all, clinical measurements of dose-area products (DAPs) and the PCXMC 2.0 Monte
      Carlo code were involved. In clinical measurements, DAPs were assessed during
      examination of 51 patients undergoing BM examinations, separated almost equally
      in three age categories, neonatal, 1- and 5-y old. Organs receiving the highest
      amounts of radiation during BM examinations were as follows: the stomach (10.4,
      10.2 and 11.1 mGy), the gall bladder (7.1, 5.8 and 5.2 mGy) and the spleen (7.5,
      8.2 and 4.3 mGy). The three values in the brackets correspond to neonatal, 1- and
      5-y-old patients, respectively. For all ages, the main contributors to the total
      organ and effective doses are the fluoroscopy projections. The average DAP values
      and absorbed doses to patient were higher for the left lateral projections. The
      REID was calculated for boys (4.8 * 10(-2), 3.0 * 10(-2) and 2.0 * 10(-2) %) for
      neonatal, 1- and 5-y old patients, respectively. The corresponding values for
      girl patients were calculated (12.1 * 10(-2), 5.5 * 10(-2) and 3.4 * 10(-2) %). 

PMID- 24876339
TI  - An alternative method using microwave power saturate in fingernail/electron
      paramagnetic resonance dosimetry.
AB  - An alternative method for fingernail/electron paramagnetic resonance (EPR)
      dosimetry valid at low doses (0-3 Gy) is suggested in this paper. The method
      consisted of two steps. The first step involved dehydrating fingernail clippings
      to remove their water content by heating them at 70  degrees C for 72 h. As the
      water content in the fingernails decreased, the variability of the EPR signals
      improved. The second step involved measuring and fitting the EPR signals at
      successive microwave power levels. A newly derived value known as 'curvature',
      which was based on the conventional peak-to-peak amplitudes of the EPR signals,
      was applied for the dosimetry. This method could be used as an alternative method
      in cases of low-radiation exposure doses (<3 Gy) or where use of the conventional
      dosimetry method is not proper for a fingernail sample. 

PMID- 24876340
TI  - Exposure estimates based on broadband ELF magnetic field measurements versus the
      ICNIRP multiple frequency rule.
AB  - The evaluation of exposure to extremely low-frequency (ELF) magnetic fields using
      broadband measurement techniques gives satisfactory results when the field has
      essentially a single frequency. Nevertheless, magnetic fields are in most cases
      distorted by harmonic components. This work analyses the harmonic components of
      the ELF magnetic field in an outdoor urban context and compares the evaluation of
      the exposure based on broadband measurements with that based on spectral
      analysis. The multiple frequency rule of the International Commission on Non
      ionizing Radiation Protection (ICNIRP) regulatory guidelines was applied. With
      the 1998 ICNIRP guideline, harmonics dominated the exposure with a 55%
      contribution. With the 2010 ICNIRP guideline, however, the primary frequency
      dominated the exposure with a 78% contribution. Values of the exposure based on
      spectral analysis were significantly higher than those based on broadband
      measurements. Hence, it is clearly necessary to determine the harmonic components
      of the ELF magnetic field to assess exposure in urban contexts.

PMID- 24876341
TI  - Applicability of EPR/alanine dosimetry for quality assurance in proton eye
      radiotherapy.
AB  - A new quality assurance and quality control method for proton eye radiotherapy
      based on electron paramagnetic resonance (EPR)/alanine dosimetry has been
      developed. It is based on Spread-Out Bragg Peak entrance dose measurement with
      alanine detectors. The entrance dose is well correlated with the dose at the
      facility isocenter, where, during the therapeutic irradiation, the tumour is
      placed. The unique alanine detector features namely keeping the dose record in a
      form of stable radiation-induced free radicals trapped in the material structure,
      and the non-destructive read-out makes this type of detector a good candidate for
      additional documentation of the patient's exposure over the therapy course. 

PMID- 24876343
TI  - Patterned hydrogel microfibers prepared using multilayered microfluidic devices
      for guiding network formation of neural cells.
AB  - Multilayered microfluidic devices with a micronozzle array structure have been
      developed to prepare unique hydrogel microfibers with highly complex cross
      sectional morphologies. Hydrogel precursor solutions with different compositions
      are introduced through vertical micronozzles, united and focused, and
      continuously gelled to form hydrogel fibers with multiple regions of different
      physicochemical composition. We prepared alginate hydrogel microfibers with
      diameters of 60 ~ 130 MUm and 4/8 parallel regions in the periphery. Neuron-like
      PC12 cells encapsulated in the parallel region, which was made of a soft hydrogel
      matrix, proliferated and formed linear intercellular networks along the fiber
      length because of the physical restrictions imposed by the relatively rigid
      regions. After cultivation for 14 days, one-millimeter-long intercellular
      networks that structurally mimic complex nerve bundles found in vivo were formed.
      The proposed fibers should be useful for producing various in vivo linear tissues
      and should be applicable to regenerative medicine and physiological studies of
      cells.

PMID- 24876342
TI  - Bioreactor for modulation of cardiac microtissue phenotype by combined static
      stretch and electrical stimulation.
AB  - We describe here a bioreactor capable of applying electrical field stimulation in
      conjunction with static strain and on-line force of contraction measurements. It
      consisted of a polydimethylsiloxane (PDMS) tissue chamber and a pneumatically
      driven stretch platform. The chamber contained eight tissue microwells (8.05 mm
      in length and 2.5 mm in width) with a pair of posts (2.78 mm in height and 0.8 mm
      in diameter) in each well to serve as fixation points and for measurements of
      contraction force. Carbon rods, stimulating electrodes, were placed into the PDMS
      chamber such that one pair stimulated four microwells. For feasibility studies,
      neonatal rat cardiomyocytes were seeded in collagen gels into the microwells.
      Following 3 days of gel compaction, electrical field stimulation at 3-4 V cm(-1)
      and 1 Hz, mechanical stimulation of 5% static strain or electromechanical
      stimulation (field stimulation at 3-4 V cm(-1), 1 Hz and 5% static strain) were
      applied for 3 days. Cardiac microtissues subjected to electromechanical
      stimulation exhibited elevated amplitude of contraction and improved sarcomere
      structure as evidenced by sarcomeric alpha-actinin, actin and troponin T staining
      compared to microtissues subjected to electrical or mechanical stimulation alone
      or non-stimulated controls. The expression of atrial natriuretic factor and brain
      natriuretic peptide was also elevated in the electromechanically stimulated
      group. 

PMID- 24876344
TI  - Effect of nano- and micro-scale topological features on alignment of muscle cells
      and commitment of myogenic differentiation.
AB  - Skeletal muscle injury can lead to severe motor deficits that adversely affect
      movement and quality of life. Current surgical treatments for skeletal muscle are
      hindered by the poor formation of organized myotube bundles at the wound site.
      Tissue-engineered skeletal muscle constructs to date have been unable to generate
      high degrees of myotube density and alignment. Generating a suitable in vitro
      tissue-engineered skeletal muscle construct requires the design of a scaffold
      that recapitulates the structural combination of nanoscale collagen fibrils and
      aligned microscale basal lamina tracks present in the native extracellular matrix
      (ECM). We hypothesized that a 3D aligned tubular porous scaffold containing
      aligned nanofibers inside the pores can mimic the native muscle tissue
      environment. We constructed a laminar section of the hypothesized scaffold with
      aligned chitosan-PCL nanofibers arranged co-axially with the aligned microscale
      chitosan scaffold bands to mimic the required myogenic environment. A 6-day study
      of C2C12 mouse myoblast cells cultured on this hybrid scaffold indicated that the
      nanofibers and scaffold bands in the scaffold played a synergetic role in
      directing cell orientation, interaction, migration and organization. Our results
      showed that aligned nanofibers mediated cell alignment and the aligned scaffold
      bands induced the formation of a more compact assembly of myotube cells as
      compared to various control substrates including chitosan films, nanofibers, and
      chitosan bands. The expression levels of both early and late-stage myogenic
      differentiation genes associated with myogenin and myosin heavy chain,
      respectively, were higher on the hybrid substrate than on control substrates. Our
      study suggests that the combination of nano and microscale topological features
      in the ECM can direct myogenic differentiation, and the hybrid material has the
      potential to improve the outcome of skeletal tissue engineering. 

PMID- 24876345
TI  - Human cognition. Foundations of human reasoning in the prefrontal cortex.
AB  - The prefrontal cortex (PFC) subserves reasoning in the service of adaptive
      behavior. Little is known, however, about the architecture of reasoning processes
      in the PFC. Using computational modeling and neuroimaging, we show here that the
      human PFC has two concurrent inferential tracks: (i) one from ventromedial to
      dorsomedial PFC regions that makes probabilistic inferences about the reliability
      of the ongoing behavioral strategy and arbitrates between adjusting this strategy
      versus exploring new ones from long-term memory, and (ii) another from polar to
      lateral PFC regions that makes probabilistic inferences about the reliability of
      two or three alternative strategies and arbitrates between exploring new
      strategies versus exploiting these alternative ones. The two tracks interact and,
      along with the striatum, realize hypothesis testing for accepting versus
      rejecting newly created strategies. 

PMID- 24876347
TI  - Hydroxylation of the surface of PbS nanocrystals passivated with oleic acid.
AB  - Controlling the structure of colloidal nanocrystals (NCs) is key to the
      generation of their complex functionality. This requires an understanding of the
      NC surface at the atomic level. The structure of colloidal PbS NCs passivated
      with oleic acid has been studied theoretically and experimentally. We show the
      existence of surface OH(-) groups, which play a key role in stabilizing the
      PbS(111) facets, consistent with x-ray photoelectron spectroscopy as well as
      other spectroscopic and chemical experiments. The role of water in the synthesis
      process is also revealed. Our model, along with existing observations of NC
      surface termination and passivation by ligands, helps to explain and predict the
      properties of NCs and their assemblies. 

PMID- 24876346
TI  - Neural migration. Structures of netrin-1 bound to two receptors provide insight
      into its axon guidance mechanism.
AB  - Netrins are secreted proteins that regulate axon guidance and neuronal migration.
      Deleted in colorectal cancer (DCC) is a well-established netrin-1 receptor
      mediating attractive responses. We provide evidence that its close relative
      neogenin is also a functional netrin-1 receptor that acts with DCC to mediate
      guidance in vivo. We determined the structures of a functional netrin-1 region,
      alone and in complexes with neogenin or DCC. Netrin-1 has a rigid elongated
      structure containing two receptor-binding sites at opposite ends through which it
      brings together receptor molecules. The ligand/receptor complexes reveal two
      distinct architectures: a 2:2 heterotetramer and a continuous ligand/receptor
      assembly. The differences result from different lengths of the linker connecting
      receptor domains fibronectin type III domain 4 (FN4) and FN5, which differs among
      DCC and neogenin splice variants, providing a basis for diverse signaling
      outcomes. 

PMID- 24876349
TI  - Recent highlights of ATVB: calcification.

PMID- 24876348
TI  - Lipoprotein subfractions highly associated with renal damage in familial
      lecithin:cholesterol acyltransferase deficiency.
AB  - OBJECTIVE: In familial lecithin:cholesterol acyltransferase (LCAT) deficiency
      (FLD), deposition of abnormal lipoproteins in the renal stroma ultimately leads
      to renal failure. However, fish-eye disease (FED) does not lead to renal damage
      although the causative mutations for both FLD and FED lie within the same LCAT
      gene. This study was performed to identify the lipoproteins important for the
      development of renal failure in genetically diagnosed FLD in comparison with FED,
      using high-performance liquid chromatography with a gel filtration column.
      APPROACH AND RESULTS: Lipoprotein profiles of 9 patients with LCAT deficiency
      were examined. Four lipoprotein fractions specific to both FLD and FED were
      identified: (1) large lipoproteins (>80 nm), (2) lipoproteins corresponding to
      large low-density lipoprotein (LDL), (3) lipoproteins corresponding to small LDL
      to large high-density lipoprotein, and (4) to small high-density lipoprotein.
      Contents of cholesteryl ester and triglyceride of the large LDL in FLD (below
      detection limit and 45.8+/-3.8%) and FED (20.7+/-6.4% and 28.0+/-6.5%) were
      significantly different, respectively. On in vitro incubation with recombinant
      LCAT, content of cholesteryl ester in the large LDL in FLD, but not in FED, was
      significantly increased (to 4.2+/-1.4%), whereas dysfunctional high-density
      lipoprotein was diminished in both FLD and FED. CONCLUSIONS: Our novel analytic
      approach using high-performance liquid chromatography with a gel filtration
      column identified large LDL and high-density lipoprotein with a composition
      specific to FLD, but not to FED. The abnormal lipoproteins were sensitive to
      treatment with recombinant LCAT and thus may play a causal role in the renal
      pathology of FLD.

PMID- 24876351
TI  - Chemokine (C-X-C motif) receptor 4 blockade by AMD3100 inhibits experimental
      abdominal aortic aneurysm expansion through anti-inflammatory effects.
AB  - OBJECTIVE: Inflammation plays a critical role in the development of abdominal
      aortic aneurysms (AAAs). Because stromal cell-derived factor 1 (SDF-1) is known
      for its ability to attract inflammatory cells, we investigated whether SDF
      1/chemokine (C-X-C motif) receptor 4 (CXCR4) axis is expressed in aneurysmal
      aortic wall and plays a role in AAA physiopathology and asked whether its
      blockade modulates AAA formation and expansion. APPROACH AND RESULTS:
      Quantitative real-time polymerase chain reaction analysis showed that SDF-1alpha
      and CXCR4 mRNA levels are increased in both human and CaCl2-induced mouse AAA
      wall and are positively correlated to the aortic diameter in mice. ELISA
      quantification and immunostaining demonstrated that, in mice, aortic SDF-1alpha
      is rapidly induced during AAA formation, first by apoptotic vascular smooth
      muscle cells in the injured media and then by adventitial macrophages once AAA is
      fully established. Using green fluorescent protein-positive (GFP(+/-)) bone
      marrow transplantation experiments, we demonstrated that aortic SDF-1
      overexpression is implicated in the recruitment of bone marrow-derived
      macrophages within the AAA wall. Furthermore, in mice, blockade of CXCR4 by
      AMD3100 decreases the infiltration of adventitial macrophages, inhibits AAA
      formation, and prevents aortic wall destruction. AMD3100 reduces the mRNA levels
      of MMP-12 and MMP-14 as well as that of inflammatory effectors MCP-1, MIP-1beta,
      MIP-2alpha, RANTES, IL-1beta, IL-6, TNF-alpha, and E-selectin. Finally, AMD3100
      stabilizes the diameter of formed, expanding AAAs in 2 experimental models.
      CONCLUSIONS: SDF-1/CXCR4 axis is upregulated in human and mouse AAAs. Blockade of
      CXCR4 with AMD3100 suppresses AAA formation and progression in two rodent models.
      Blockade of SDF-1/CXCR4 axis may represent a new strategy to limit progression of
      small human AAAs.

PMID- 24876350
TI  - Mediation of cardiovascular risk factor effects through subclinical vascular
      disease: the Multi-Ethnic Study of Atherosclerosis.
AB  - OBJECTIVE: It is unclear to what extent subclinical cardiovascular disease (CVD)
      such as coronary artery calcium (CAC), carotid intima-media thickness (CIMT), and
      brachial flow-mediated dilation (FMD) are mediators of the known associations
      between traditional cardiovascular risk factors and incident CVD events. We
      assessed the portion of the effects of risk factors on incident CVD events that
      are mediated through CAC, CIMT, and FMD. APPROACH AND RESULTS: Six thousand three
      hundred fifty-five of 6814 Multi-Ethnic Study of Atherosclerosis participants
      were included. Nonlinear implementation of structural equation modeling (STATA
      mediation package) was used to assess whether CAC, CIMT, or FMD are mediators of
      the association between traditional risk factors and incident CVD event. Mean age
      was 62 years, with 47% men, 12% diabetics, and 13% current smokers. After a mean
      follow-up of 7.5 years, there were 539 CVD adjudicated events. CAC showed the
      highest mediation while FMD showed the least. Age had the highest percent of
      total effect mediated via CAC for CVD outcomes, whereas current cigarette smoking
      had the least percent of total effect mediated via CAC (percent [95% confidence
      interval]: 80.2 [58.8-126.7] versus 10.6 [6.1-38.5], respectively). Body mass
      index showed the highest percent of total effect mediated via CIMT (17.7 [11.6
      38.9]); only a negligible amount of the association between traditional risk
      factors and CVD was mediated via FMD. CONCLUSIONS: Many of the risk factors for
      incident CVD (other than age, sex, and body mass index) showed a modest level of
      mediation via CAC, CIMT, and FMD, suggesting that current subclinical CVD markers
      may not be optimal intermediaries for gauging upstream risk factor modification.

PMID- 24876353
TI  - Skin autofluorescence associates with vascular calcification in chronic kidney
      disease.
AB  - OBJECTIVE: This study aims to evaluate the relationship between tissue advanced
      glycation end products, as reflected by skin autofluorescence, and vascular
      calcification in chronic kidney disease. APPROACH AND RESULTS: Three hundred
      patients with stage 3 to 5 chronic kidney disease underwent multislice computed
      tomography to estimate total coronary artery calcium score (CACS) and had tissue
      advanced glycation end product assessed using a skin autofluorescence reader.
      Intact parathyroid hormone (P<0.001) displaced estimated glomerular filtration
      rate as third most significant factor associated with skin autofluorescence after
      age (P<0.001) and diabetes mellitus (P<0.001) in multiple regression analysis. On
      univariate multinomial logistic regression analysis, every 1-U increase in skin
      autofluorescence was associated with a 7.43-fold (95% confidence intervals, 3.59
      15.37; P<0.001) increased odds of having CACS >=400 compared with those with zero
      CACS. Skin autofluorescence retained significance in predicting CACS >=400 (odds
      ratio, 3.63; 95% confidence intervals, 1.44-9.18; P=0.006) when adjusting for
      age, sex, serum calcium, phosphate, albumin, C-reactive protein, lipids, blood
      pressure, estimated glomerular filtration rate, and intact parathyroid hormone
      but marginally lost significance when additionally adjusting for diabetes
      mellitus (odds ratio, 2.23; 95% confidence intervals, 0.81-6.14; P=0.1).
      Combination of diabetes mellitus and higher intact parathyroid hormone was
      associated with greater skin autofluorescence and CACS versus those without
      diabetes mellitus and having lower intact parathyroid hormone. CONCLUSIONS:
      Tissue advanced glycation end product, as reflected by skin autofluorescence,
      showed a significant novel association with vascular calcification in chronic
      kidney disease. These data suggest that increased tissue advanced glycation end
      product may contribute to vascular calcification in chronic kidney disease and
      diabetes mellitus and warrant further experimental investigation.

PMID- 24876352
TI  - Estrogen effects on vascular inflammation are age dependent: role of estrogen
      receptors.
AB  - OBJECTIVE: 17beta-Estradiol (E2) offers cardiovascular protection in young female
      animals and postmenopausal women. In contrast, randomized trials of menopausal
      hormones performed in older women have shown harm or no cardiovascular benefit.
      We hypothesize that E2 effects on vascular inflammation are age dependent.
      APPROACH AND RESULTS: Young (10 weeks) and aged (52 weeks) female C57BL/6 mice
      were used as source for primary cultures of bone marrow-derived macrophages
      (BMMs) and vascular smooth muscle cells (VSMCs). E2 pretreatment of cells derived
      from young mice attenuated C-reactive protein (CRP)-induced expression of
      inflammatory mediators. In contrast, E2 pretreatment of cells from aged mice did
      not alter (BMMs) or paradoxically exaggerated (VSMCs) inflammatory mediator
      response to CRP. Using E2 receptor (ER) knockout mice, we demonstrated that E2
      regulates inflammatory response to CRP in BMMs via ERalpha and in VSMCs via
      ERbeta. BMMs derived from aged (versus young) mice expressed significantly less
      ERalpha mRNA and protein. A selective ligand of the novel ER GPR30 reproduced the
      E2 effects in BMMs and VSMCs. Unlike in young mice, E2 did not reduce neointima
      formation in ligated carotid arteries of aged CRP transgenic mice. CONCLUSIONS:
      E2 attenuates inflammatory response to CRP in BMMs and VSMCs derived from young
      but not aged mice and reduces neointima formation in injured carotid arteries of
      young but not aged CRP transgenic mice. ERalpha expression in BMMs is greatly
      diminished with aging. These data suggest that vasoprotective effects of E2 are
      age dependent and may explain the vasotoxic effects of E2 seen in clinical trials
      of postmenopausal women.

PMID- 24876354
TI  - Shear stress-initiated signaling and its regulation of endothelial function.
AB  - Atherosclerosis develops preferentially at branches and curvatures of the
      arterial tree, where blood flow pattern is disturbed rather than being laminar,
      and wall shear stress has an irregular distribution without defined directions.
      The endothelium in the atherosusceptible regions, in comparison to that in
      atheroresistant regions, shows activation of proproliferative and proinflammatory
      gene expressions, reduced production of nitric oxide (NO), increased leukocyte
      adhesion, and permeability, as well as other atheroprone phenotypes. Differences
      in gene expressions and cell phenotypes have been detected in endothelia residing
      in native atherosusceptible and atheroresistant regions of the arteries, or in
      arteries from animal models with artificial creation of disturbed flow. Similar
      results have also been shown in in vitro systems that apply controlled shear
      stresses with or without clear directions to cultured endothelial cells in fluid
      dynamically designed flow-loading devices. The available evidence indicates that
      the coordination of multiple signaling networks, rather than individual separate
      pathways, links the mechanical signals to specific genetic circuitries in
      orchestrating the mechanoresponsive networks to evoke comprehensive genetic and
      functional responses. 

PMID- 24876355
TI  - Cardiac and kidney markers for cardiovascular prediction in individuals with
      chronic kidney disease: the Atherosclerosis Risk in Communities study.
AB  - OBJECTIVE: Traditional predictors suboptimally predict cardiovascular disease
      (CVD) in individuals with chronic kidney disease (CKD). This study compared 5
      nontraditional cardiac and kidney markers on the improvement of cardiovascular
      prediction among those with CKD. APPROACH AND RESULTS: Among 8622 participants
      aged 52 to 75 years in the Atherosclerosis Risk in Communities (ARIC) Study,
      cardiac troponin T, N-terminal pro-B-type natriuretic peptide, cystatin C, beta2
      microglobulin, and beta-trace protein were compared for improvement in predicting
      incident CVD after stratifying by CKD status (940 participants with CKD [kidney
      dysfunction or albuminuria]). During a median follow-up of 11.9 years, there were
      1672 CVD events including coronary disease, stroke, and heart failure (336 cases
      in CKD). Every marker was independently associated with incident CVD in
      participants with and without CKD. The adjusted hazard ratios (per 1 SD) were
      larger for cardiac markers than for kidney markers, particularly in CKD (1.61
      [95% confidence interval, 1.43-1.81] for cardiac troponin T, 1.50 [1.34-1.68] for
      N-terminal pro-B-type natriuretic peptide, and <1.26 for kidney markers).
      Particularly in CKD group, cardiac markers compared with kidney markers
      contributed to greater c-statistic increment (0.032-0.036 versus 0.012-0.015 from
      0.679 with only conventional predictors in CKD and 0.008-0.011 versus 0.002-0.010
      from 0.697 in non-CKD) and categorical net reclassification improvement (0.086
      0.127 versus 0.020-0.066 in CKD and 0.057-0.077 versus 0.014-0.048 in non-CKD).
      The superiority of cardiac markers was largely consistent in individual CVD
      outcomes. CONCLUSIONS: A greater improvement in cardiovascular prediction was
      observed for cardiac markers than for kidney markers in people with CKD. These
      results suggest that cardiac troponin T and N-terminal pro-B-type natriuretic
      peptide are useful for better CVD risk classification in this population.

PMID- 24876357
TI  - Reductions in central venous pressure by lower body negative pressure or blood
      loss elicit similar hemodynamic responses.
AB  - The purpose of this study was to compare hemodynamic and blood analyte responses
      to reduced central venous pressure (CVP) and pulse pressure (PP) elicited during
      graded lower body negative pressure (LBNP) to those observed during graded blood
      loss (BL) in conscious humans. We hypothesized that the stimulus-response
      relationships of CVP and PP to hemodynamic responses during LBNP would mimic
      those observed during BL. We assessed CVP, PP, heart rate, mean arterial pressure
      (MAP), and other hemodynamic markers in 12 men during LBNP and BL. Blood samples
      were obtained for analysis of catecholamines, hematocrit, hemoglobin, arginine
      vasopressin, and blood gases. LBNP consisted of 5-min stages at 0, 15, 30, and 45
      mmHg of suction. BL consisted of 5 min at baseline and following three stages of
      333 ml of hemorrhage (1,000 ml total). Individual r(2) values and linear
      regression slopes were calculated to determine whether the stimulus (CVP and PP)
      hemodynamic response trajectories were similar between protocols. The CVP-MAP
      trajectory was the only CVP-response slope that was statistically different
      during LBNP compared with BL (0.93 +/- 0.27 vs. 0.13 +/- 0.26; P = 0.037). The PP
      heart rate trajectory was the only PP-response slope that was statistically
      different during LBNP compared with BL (-1.85 +/- 0.45 vs. -0.46 +/- 0.27; P =
      0.024). Norepinephrine, hematocrit, and hemoglobin were all lower at termination
      in the BL protocol compared with LBNP (P < 0.05). Consistent with our hypothesis,
      LBNP mimics the hemodynamic stimulus-response trajectories observed during BL
      across a significant range of CVP in humans.

PMID- 24876356
TI  - Sustained AS160 and TBC1D1 phosphorylations in human skeletal muscle 30 min after
      a single bout of exercise.
AB  - BACKGROUND: phosphorylation of AS160 and TBC1D1 plays an important role for GLUT4
      mobilization to the cell surface. The phosphorylation of AS160 and TBC1D1 in
      humans in response to acute exercise is not fully characterized. OBJECTIVE: to
      study AS160 and TBC1D1 phosphorylation in human skeletal muscle after aerobic
      exercise followed by a hyperinsulinemic euglycemic clamp. DESIGN: eight healthy
      men were studied on two occasions: 1) in the resting state and 2) in the hours
      after a 1-h bout of ergometer cycling. A hyperinsulinemic euglycemic clamp was
      initiated 240 min after exercise and in a time-matched nonexercised control
      condition. We obtained muscle biopsies 30 min after exercise and in a time
      matched nonexercised control condition (t = 30) and after 30 min of insulin
      stimulation (t = 270) and investigated site-specific phosphorylation of AS160 and
      TBC1D1. RESULTS: phosphorylation on AS160 and TBC1D1 was increased 30 min after
      the exercise bout, whereas phosphorylation of the putative upstream kinases, Akt
      and AMPK, was unchanged compared with resting control condition. Exercise
      augmented insulin-stimulated phosphorylation on AS160 at Ser(341) and Ser(704)
      270 min after exercise. No additional exercise effects were observed on insulin
      stimulated phosphorylation of Thr(642) and Ser(588) on AS160 or Ser(237) and
      Thr(596) on TBC1D1. CONCLUSIONS: AS160 and TBC1D1 phosphorylations were evident
      30 min after exercise without simultaneously increased Akt and AMPK
      phosphorylation. Unlike TBC1D1, insulin-stimulated site-specific AS160
      phosphorylation is modified by prior exercise, but these sites do not include
      Thr(642) and Ser(588). Together, these data provide new insights into
      phosphorylation of key regulators of glucose transport in human skeletal muscle.

PMID- 24876358
TI  - Ventricular structure, function, and mechanics at high altitude: chronic
      remodeling in Sherpa vs. short-term lowlander adaptation.
AB  - Short-term, high-altitude (HA) exposure raises pulmonary artery systolic pressure
      (PASP) and decreases left-ventricular (LV) volumes. However, relatively little is
      known of the long-term cardiac consequences of prolonged exposure in Sherpa, a
      highly adapted HA population. To investigate short-term adaptation and potential
      long-term cardiac remodeling, we studied ventricular structure and function in
      Sherpa at 5,050 m (n = 11; 31 +/- 13 yr; mass 68 +/- 10 kg; height 169 +/- 6 cm)
      and lowlanders at sea level (SL) and following 10 +/- 3 days at 5,050 m (n = 9;
      34 +/- 7 yr; mass 82 +/- 10 kg; height 177 +/- 6 cm) using conventional and
      speckle-tracking echocardiography. At HA, PASP was higher in Sherpa and
      lowlanders compared with lowlanders at SL (both P < 0.05). Sherpa had smaller
      right-ventricular (RV) and LV stroke volumes than lowlanders at SL with lower RV
      systolic strain (P < 0.05) but similar LV systolic mechanics. In contrast to LV
      systolic mechanics, LV diastolic, untwisting velocity was significantly lower in
      Sherpa compared with lowlanders at both SL and HA. After partial acclimatization,
      lowlanders demonstrated no change in the RV end-diastolic area; however, both RV
      strain and LV end-diastolic volume were reduced. In conclusion, short-term
      hypoxia induced a reduction in RV systolic function that was also evident in
      Sherpa following chronic exposure. We propose that this was consequent to a
      persistently higher PASP. In contrast to the RV, remodeling of LV volumes and
      normalization of systolic mechanics indicate structural and functional adaptation
      to HA. However, altered LV diastolic relaxation after chronic hypoxic exposure
      may reflect differential remodeling of systolic and diastolic LV function. 

PMID- 24876360
TI  - Length-force characteristics of in vivo human muscle reflected by supersonic
      shear imaging.
AB  - Recently, an ultrasound-based elastography technique has been used to measure
      stiffness (shear modulus) of an active human muscle along the axis of
      contraction. Using this technique, we explored 1) whether muscle shear modulus,
      like muscle force, is length dependent; and 2) whether the length dependence of
      muscle shear modulus is consistent between electrically elicited and voluntary
      contractions. From nine healthy participants, ankle joint torque and shear
      modulus of the tibialis anterior muscle were measured at five different ankle
      joint angles during tetanic contractions and during maximal voluntary
      contractions. Fascicle length, pennation angle, and tendon moment arm length of
      the tetanized tibialis anterior calculated from ultrasound images were used to
      reveal the length-dependent changes in muscle force and shear modulus. Over the
      range of joint angles examined, both force and shear modulus of the tetanized
      muscle increased with increasing fascicle length. Regression analysis of
      normalized data revealed a significant linear relationship between force and
      shear modulus (R(2) = 0.52, n = 45, P < 0.001). Although the length dependence of
      shear modulus was consistent, irrespective of contraction mode, the slope of
      length-shear modulus relationship was steeper during maximal voluntary
      contractions than during tetanic contractions. These results provide novel
      evidence that length-force relationship, one of the most fundamental
      characteristics of muscle, can be inferred from in vivo imaging of shear modulus
      in the tibialis anterior muscle. Furthermore, the estimation of length-force
      relationship may be applicable to voluntary contractions in which neural and
      mechanical interactions of multiple muscles are involved. 

PMID- 24876361
TI  - Direct measurement of cell-free DNA from serially collected capillary plasma
      during incremental exercise.
AB  - To investigate the kinetics of cell-free DNA (cfDNA) due to exercise, we
      established a direct real-time PCR for the quantification of cfDNA from
      unpurified capillary plasma by amplification of a 90- and a 222-bp multilocus
      L1PA2 sequence. Twenty-six male athletes performed an incremental treadmill test.
      For cfDNA measurement, capillary samples were collected serially from the
      fingertip preexercise, during, and several times postexercise. Venous blood was
      drawn before and immediately after exercise to compare capillary and venous cfDNA
      values. To elucidate the strongest association of cfDNA accumulations with either
      cardiorespiratory or metabolic function during exercise, capillary cfDNA values
      were correlated with standard measures like heart rate, oxygen consumption, or
      lactate concentrations. The venous cfDNA concentrations were significantly higher
      compared with the capillary plasma, but in both fractions cfDNA increased 9.8
      fold and the values correlated significantly (r = 0.796). During incremental
      treadmill running, the capillary cfDNA concentrations increased nearly parallel
      to the lactate values. The values correlated best with heart rate and energy
      expenditure, followed by oxygen consumption, Borg values, and lactate levels
      (0.710 <= r >= 0.808). With this article, we present a sensitive procedure for
      the direct quantification of cfDNA in unpurified capillary plasma instead of
      purified venous plasma. Further studies should investigate the differences
      between capillary and venous cfDNA that might mirror different physiological
      mechanisms. Enhanced cardiorespiratory function during exercise might lead to the
      accumulation of cfDNA via the release of stress hormones that already increase at
      intensities below the anaerobic threshold. Furthermore, cfDNA might be released
      by neutrophil extracellular traps.

PMID- 24876359
TI  - Distribution of normal human left ventricular myofiber stress at end diastole and
      end systole: a target for in silico design of heart failure treatments.
AB  - Ventricular wall stress is believed to be responsible for many physical
      mechanisms taking place in the human heart, including ventricular remodeling,
      which is frequently associated with heart failure. Therefore, normalization of
      ventricular wall stress is the cornerstone of many existing and new treatments
      for heart failure. In this paper, we sought to construct reference maps of normal
      ventricular wall stress in humans that could be used as a target for in silico
      optimization studies of existing and potential new treatments for heart failure.
      To do so, we constructed personalized computational models of the left ventricles
      of five normal human subjects using magnetic resonance images and the finite
      element method. These models were calibrated using left ventricular volume data
      extracted from magnetic resonance imaging (MRI) and validated through comparison
      with strain measurements from tagged MRI (950 +/- 170 strain
      comparisons/subject). The calibrated passive material parameter values were C0 =
      0.115 +/- 0.008 kPa and B0 = 14.4 +/- 3.18; the active material parameter value
      was Tmax = 143 +/- 11.1 kPa. These values could serve as a reference for future
      construction of normal human left ventricular computational models. The
      differences between the predicted and the measured circumferential and
      longitudinal strains in each subject were 3.4 +/- 6.3 and 0.5 +/- 5.9%,
      respectively. The predicted end-diastolic and end-systolic myofiber stress fields
      for the five subjects were 2.21 +/- 0.58 and 16.54 +/- 4.73 kPa, respectively.
      Thus these stresses could serve as targets for in silico design of heart failure
      treatments.

PMID- 24876362
TI  - Differential regulation of the fiber type-specific gene expression of the
      sarcoplasmic reticulum calcium-ATPase isoforms induced by exercise training.
AB  - The regulatory role of adenosine monophosphate-activated protein kinase (AMPK)
      alpha2 on sarcoplasmic reticulum calcium-ATPase (SERCA) 1a and SERCA2a in
      different skeletal muscle fiber types has yet to be elucidated. Sedentary (Sed)
      or exercise-trained (Ex) wild-type (WT) and AMPKalpha2-kinase dead (KD)
      transgenic mice, which overexpress a mutated and inactivated AMPKalpha2 subunit,
      were utilized to characterize how genotype or exercise training influenced the
      regulation of SERCA isoforms in gastrocnemius. As expected, both Sed and Ex KD
      mice had >40% lower AMPK phosphorylation and 30% lower SERCA1a protein than WT
      mice (P < 0.05). In contrast, SERCA2a protein was not different among KD and WT
      mice. Exercise increased SERCA1a and SERCA2a protein content among WT and KD
      mice, compared with their Sed counterparts. Maximal SERCA activity was lower in
      KD mice, compared with WT. Total phospholamban protein was higher in KD mice than
      in WT and lower in Ex compared with Sed mice. Exercise training increased
      phospholamban Ser(16) phosphorylation in WT mice. Laser capture microdissection
      and quantitative PCR indicated that SERCA1a mRNA expression among type I fibers
      was not altered by genotype or exercise, but SERCA2a mRNA was increased 30-fold
      in WT+Ex, compared with WT+Sed. In contrast, the exercise-stimulated increase for
      SERCA2a mRNA was blunted in KD mice. Exercise upregulated SERCA1a and SERCA2a
      mRNA among type II fibers, but was not altered by genotype. Collectively, these
      data suggest that exercise differentially influences SERCA isoform expression in
      type I and type II fibers. Additionally, AMPKalpha2 influences the regulation of
      SERCA2a mRNA in type I skeletal muscle fibers following exercise training. 

PMID- 24876364
TI  - Four postmortem case reports with quantitative detection of the synthetic
      cannabinoid, 5F-PB-22.
AB  - In January 2014, the US government temporarily designated 5F-PB-22, along with
      three other synthetic cannabinoids (AB-FUBINACA, ADB-PINACA and PB-22), into
      Schedule I. Over the course of a 4-month time period (July-October 2013), our
      laboratory quantitatively identified 5F-PB-22 in specimens obtained from four
      postmortem cases. We describe the four cases, to include pertinent autopsy
      findings and decedent histories, together with quantitative results for 5F-PB-22
      determined in postmortem blood and antemortem serum. Samples were prepared via a
      liquid-liquid extraction at pH 10.2 into hexane : ethyl acetate. Instrumental
      analysis was achieved with liquid chromatography coupled with electrospray
      ionization tandem mass spectrometry operating in multiple reaction monitoring
      mode. Two ion transitions were monitored for the analyte of interest, and one ion
      transition was monitored for the internal standard. The observed concentration
      range of 5F-PB-22 is 1.1-1.5 ng/mL for three postmortem blood specimens and one
      antemortem serum specimen. Three of the decedents experienced abrupt, sudden
      death; however, one decedent expired after a rapidly deteriorating hospital
      course. 

PMID- 24876365
TI  - An unusual presentation of aplastic anaemia: compartment syndrome.
AB  - This is a case of a previously fit and healthy 17-year-old man presenting with
      atraumatic forearm compartment syndrome. On his initial blood film, he was found
      to have a pancytopenia and was subsequently diagnosed with aplastic anaemia. His
      compartment syndrome was treated with urgent fasciotomy after correction of his
      pancytopenia. He made a good functional recovery with only a very minor deficit,
      and no recurrence of his compartment syndrome. He has undergone a successful bone
      marrow transplant for treatment of his aplastic anaemia. 

PMID- 24876366
TI  - Vaginal repair of vaginal vault dehiscence after postpartum hysterectomy.
AB  - Vaginal vault dehiscence (VVD) may occur rarely after hysterectomy. Although
      mostly, a vaginal cuff dehiscence is seen after robotic or laparoscopic
      hysterectomy, it may also be observed as a complication of abdominal or vaginal
      hysterectomy. Vaginal repair is one of the techniques used for VVD. Here, we will
      describe a case of vaginally repaired VVD, associated with intra-abdominal
      hematoma after postpartum hysterectomy. 

PMID- 24876367
TI  - Successful embolization of vulval varices arising from the external pudendal
      vein?.
AB  - Varicose veins in the vulvar and peri-vulvar area are seen in 4% of women and
      most commonly seen during pregnancy. It is thought to be as a direct result of
      the presence of ovarian and pelvic varicosities. Diagnostic modalities used in
      the investigation of this condition included pelvic ultrasound, computed
      venography, magnetic resonance venography and catheter-directed venography. The
      treatment options in the past were hysterectomy and/or ligation of ovarian veins
      by open or laparoscopic approach. Modern techniques involve embolization of the
      varicosity via radiological techniques. In this case the patient presented with
      vulval and upper thigh varices associated with pelvic pain. They were located to
      be from the superficial external pudendal vein, which is not a common source but
      worth considering with other causes. They were treated successfully with
      fluoroscopy-guided embolization. 

PMID- 24876368
TI  - Fetus-in-fetu: a pediatric rarity.
AB  - Fetus-in-fetu (FIF) is a rare entity resulting from abnormal embryogenesis in
      diamniotic monochorionic twins, being first described by Johann Friedrich Meckel
      (1800s). This occurs when a vertebrate fetus is enclosed in a normally growing
      fetus. Clinical manifestations vary. Detection is most often in infancy, the
      oldest reported age being 47. We report the case of a 4-day-old girl who was
      referred postnatally following a prenatal fetal scan which had revealed the
      presence of a multi-loculated retroperitoneal mass lesion with calcifications
      within. A provisional radiological diagnosis of FIF was made. Elective laparotomy
      revealed a well encapsulated retroperitoneal mass containing among other
      structures a skull vault and rudimentary limb buds. Recovery was uneventful. Here
      we discuss the difference between FIF and teratomas, risks of non-operative
      therapy and the role of serology in surveillance and detection of malignant
      change. 

PMID- 24876363
TI  - Altered nutrient response of mTORC1 as a result of changes in REDD1 expression:
      effect of obesity vs. REDD1 deficiency.
AB  - Although aberrant mTORC1 signaling has been well established in models of
      obesity, little is known about its repressor, REDD1. Therefore, the initial goal
      of this study was to determine the role of REDD1 on mTORC1 in obese skeletal
      muscle. REDD1 expression (protein and message) and mTORC1 signaling (S6K1, 4E
      BP1, raptor-mTOR association, Rheb GTP) were examined in lean vs. ob/ob and REDD1
      wild-type (WT) vs. knockout (KO) mice, under conditions of altered nutrient
      intake [fasted and fed or diet-induced obesity (10% vs. 60% fat diet)]. Despite
      higher (P < 0.05) S6K1 and 4E-BP1 phosphorylation, two models of obesity (ob/ob
      and diet-induced) displayed elevated (P < 0.05) skeletal muscle REDD1 expression
      compared with lean or low-fat-fed mouse muscle under fasted conditions. The ob/ob
      mice displayed elevated REDD1 expression (P < 0.05) that coincided with aberrant
      mTORC1 signaling (hyperactive S6K1, low raptor-mTOR binding, elevated Rheb GTP; P
      < 0.05) under fasted conditions, compared with the lean, which persisted in a
      dysregulated fashion under fed conditions. REDD1 KO mice gained limited body mass
      on a high-fat diet, although S6K1 and 4E-BP1 phosphorylation remained elevated (P
      < 0.05) in both the low-fat and high-fat-fed KO vs. WT mice. Similarly, the REDD1
      KO mouse muscle displayed blunted mTORC1 signaling responses (S6K1 and 4E-BP1,
      raptor-mTOR binding) and circulating insulin under fed conditions vs. the robust
      responses (P < 0.05) in the WT fed mouse muscle. These studies suggest that REDD1
      in skeletal muscle may serve to limit hyperactive mTORC1, which promotes aberrant
      mTORC1 signaling responses during altered nutrient states. 

PMID- 24876369
TI  - Progression of malrotation into volvulus in an adult after appendectomy.
AB  - Among the pediatric population malrotation is the most common cause of volvulus.
      This paper describes a case of adult malrotation, which progressed to volvulus
      shortly after appendectomy. It also reviews clinical presentations and diagnostic
      tools, discusses the recommended management, and considerations when addressing
      of this rare malady. 

PMID- 24876370
TI  - Primary malignant melanoma of the oesophagus: two case reports.
AB  - Primary malignant melanoma of the oesophagus is a rare and aggressive malignancy.
      This tumour entity accounts for 0.1-0.2% of all oesophageal malignancies and risk
      factors are yet to be established, although melanosis of the oesophagus may
      reflect its precursor form. Dysphagia is the commonest symptom. On gastroscopy,
      it appears as an elevated pigmented mass with satellite lesions in some cases.
      Unfortunately, most patients present late with metastatic disease. The prognosis
      is poor with a mean survival time post-operatively of 10-14 months and a 5-year
      survival rate of 4.5%. Although adjuvant therapy offers some loco-regional
      control, complete surgical resection offers the best hope for survival. 

PMID- 24876371
TI  - A rare case of umbilical hernia containing the pancreas.
AB  - We present an extremely rare case of anterior abdominal wall hernia containing
      multiple viscera and the pancreas in a morbidly obese patient. 

PMID- 24876372
TI  - Chopart arthrodesis with graft bone from the iliac crest after a traumatic
      subamputation of the forefoot: surgical technique.
AB  - We present a 49-year-old man with a traumatic subamputation of the forefoot,
      associated with lacerated wound in correspondence of the dorsal surface of the
      right foot, with injuries of tendinous, ligamentous and vascular structures and
      with the loss of talus head. The patient underwent salvage arthrodesis of the
      talonavicular and calcanealcuboid joints with graft bone harvested from the iliac
      crest. The patient was re-evaluated during a clinical and radiographic follow-up.
      The arthrodesis was consolidated in ~3 months. There were no infectious problems
      and the patient has resumed normal work activities. At a sixth month follow-up,
      the patient had returned to work and remained pain free while walking. Early
      anatomic reduction, stable fixation and ligament reconstruction are essential for
      a good outcome. Primary arthrodesis is a viable option for severe midfoot
      fracture dislocations, because it facilitates rehabilitation and functional
      recovery and obviates the need for a secondary arthrodesis should arthritis
      arise. 

PMID- 24876373
TI  - De Garengeot's hernia: diagnosis and surgical management of a rare type of
      femoral hernia.
AB  - De Garengeot's hernia is quite rare and is a femoral hernia that contains a
      vermiform appendix and can present as a painful, tender swelling or an
      asymptomatic lump. We present the case of a 70-year-old patient who presented to
      our surgical unit after being referred for diagnostic imaging of an asymptomatic
      groin lump which was found to be a De Garengeot's hernia. She had an open repair
      of her femoral hernia and laparoscopic appendicectomy. Her post-operative stay
      was uneventful. De Garengeot's hernia is rare; however, imaging is usually
      required to make a diagnosis preoperatively. Management is usually surgical with
      simultaneous repair of the femoral hernia and appendicectomy. 

PMID- 24876374
TI  - Small bowel obstruction secondary to bilateral obturator hernia: a rare
      occurrence.
AB  - Obturator hernia (OH) is a rare type of pelvic hernia. It can cause significant
      morbidity and mortality, especially in the elderly age group. Delayed treatment
      is associated with high rates of strangulation (25-100%). We present an 88-year
      old woman who presented with symptoms of bowel obstruction and right hip pain.
      Computed tomography (CT) abdomen revealed bilateral OHs and bowel obstruction
      secondary to the right OH. She was managed conservatively due to her age and co
      morbidities and her bowel obstruction subsequently resolved. She was discharged,
      only to re-present 1 month later with similar complaints. A repeat CT scan
      revealed bilateral OHs and bowel obstruction due to the left OH. She underwent
      midline laparatomy and both OHs were reduced. The right OH was fixed with
      polypropylene mesh plug and the left OH was fixed with primary closure. The
      patient recovered and no recurrence was noted during follow-up. 

PMID- 24876375
TI  - CAVER Analyst 1.0: graphic tool for interactive visualization and analysis of
      tunnels and channels in protein structures.
AB  - The transport of ligands, ions or solvent molecules into proteins with buried
      binding sites or through the membrane is enabled by protein tunnels and channels.
      CAVER Analyst is a software tool for calculation, analysis and real-time
      visualization of access tunnels and channels in static and dynamic protein
      structures. It provides an intuitive graphic user interface for setting up the
      calculation and interactive exploration of identified tunnels/channels and their
      characteristics. AVAILABILITY AND IMPLEMENTATION: CAVER Analyst is a multi
      platform software written in JAVA. Binaries and documentation are freely
      available for non-commercial use at http://www.caver.cz.

PMID- 24876376
TI  - Reference-free prediction of rearrangement breakpoint reads.
AB  - MOTIVATION: Chromosome rearrangement events are triggered by atypical breaking
      and rejoining of DNA molecules, which are observed in many cancer-related
      diseases. The detection of rearrangement is typically done by using short reads
      generated by next-generation sequencing (NGS) and combining the reads with
      knowledge of a reference genome. Because structural variations and genomes differ
      from one person to another, intermediate comparison via a reference genome may
      lead to loss of information. RESULTS: In this article, we propose a reference
      free method for detecting clusters of breakpoints from the chromosomal
      rearrangements. This is done by directly comparing a set of NGS normal reads with
      another set that may be rearranged. Our method SlideSort-BPR (breakpoint reads)
      is based on a fast algorithm for all-against-all comparisons of short reads and
      theoretical analyses of the number of neighboring reads. When applied to a
      dataset with a sequencing depth of 100*, it finds ~ 88% of the breakpoints
      correctly with no false-positive reads. Moreover, evaluation on a real prostate
      cancer dataset shows that the proposed method predicts more fusion transcripts
      correctly than previous approaches, and yet produces fewer false-positive reads.
      To our knowledge, this is the first method to detect breakpoint reads without
      using a reference genome. AVAILABILITY AND IMPLEMENTATION: The source code of
      SlideSort-BPR can be freely downloaded from https://code.google.com/p/slidesort
      bpr/.

PMID- 24876377
TI  - PatternCNV: a versatile tool for detecting copy number changes from exome
      sequencing data.
AB  - MOTIVATION: Exome sequencing (exome-seq) data, which are typically used for
      calling exonic mutations, have also been utilized in detecting DNA copy number
      variations (CNVs). Despite the existence of several CNV detection tools, there is
      still a great need for a sensitive and an accurate CNV-calling algorithm with
      built-in QC steps, and does not require a paired reference for each sample.
      RESULTS: We developed a novel method named PatternCNV, which (i) accounts for the
      read coverage variations between exons while leveraging the consistencies of this
      variability across different samples; (ii) reduces alignment BAM files to WIG
      format and therefore greatly accelerates computation; (iii) incorporates multiple
      QC measures designed to identify outlier samples and batch effects; and (iv)
      provides a variety of visualization options including chromosome, gene and exon
      level views of CNVs, along with a tabular summarization of the exon-level CNVs.
      Compared with other CNV-calling algorithms using data from a lymphoma exome-seq
      study, PatternCNV has higher sensitivity and specificity. AVAILABILITY AND
      IMPLEMENTATION: The software for PatternCNV is implemented using Perl and R, and
      can be used in Mac or Linux environments. Software and user manual are available
      at http://bioinformaticstools.mayo.edu/research/patterncnv/, and R package at
      https://github.com/topsoil/patternCNV/.

PMID- 24876378
TI  - Reelin induces Erk1/2 signaling in cortical neurons through a non-canonical
      pathway.
AB  - Reelin is an extracellular protein that controls many aspects of pre- and
      postnatal brain development and function. The molecular mechanisms that mediate
      postnatal activities of Reelin are not well understood. Here, we first set out to
      express and purify the full length Reelin protein and a biologically active
      central fragment. Second, we investigated in detail the signal transduction
      mechanisms elicited by these purified Reelin proteins in cortical neurons.
      Unexpectedly, we discovered that the full-length Reelin moiety, but not the
      central fragment, is capable of activating Erk1/2 signaling, leading to increased
      p90RSK phosphorylation and the induction of immediate-early gene expression.
      Remarkably, Erk1/2 activation is not mediated by the canonical signal
      transduction pathway, involving ApoER2/VLDLR and Dab1, that mediates other
      functions of Reelin in early brain development. The activation of Erk1/2
      signaling likely contributes to the modulation of neuronal maturation and
      synaptic plasticity by Reelin in the postnatal and adult brain. 

PMID- 24876379
TI  - The development and maintenance of paclitaxel-induced neuropathic pain require
      activation of the sphingosine 1-phosphate receptor subtype 1.
AB  - The ceramide-sphingosine 1-phosphate (S1P) rheostat is important in regulating
      cell fate. Several chemotherapeutic agents, including paclitaxel (Taxol), involve
      pro-apoptotic ceramide in their anticancer effects. The ceramide-to-S1P pathway
      is also implicated in the development of pain, raising the intriguing possibility
      that these sphingolipids may contribute to chemotherapy- induced painful
      peripheral neuropathy, which can be a critical dose-limiting side effect of many
      widely used chemotherapeutic agents.We demonstrate that the development of
      paclitaxel-induced neuropathic pain was associated with ceramide and S1P
      formation in the spinal dorsal horn that corresponded with the engagement of S1P
      receptor subtype 1 (S1PR(1))- dependent neuroinflammatory processes as follows:
      activation of redox-sensitive transcription factors (NFkappaB) and MAPKs (ERK and
      p38) as well as enhanced formation of pro-inflammatory and neuroexcitatory
      cytokines (TNF-alpha and IL-1beta). Intrathecal delivery of the S1PR1 antagonist
      W146 reduced these neuroinflammatory processes but increased IL-10 and IL-4,
      potent anti-inflammatory/ neuroprotective cytokines. Additionally, spinal W146
      reversed established neuropathic pain. Noteworthy, systemic administration of the
      S1PR1 modulator FTY720 (Food and Drug Administration- approved for multiple
      sclerosis) attenuated the activation of these neuroinflammatory processes and
      abrogated neuropathic pain without altering anticancer properties of paclitaxel
      and with beneficial effects extended to oxaliplatin. Similar effects were
      observed with other structurally and chemically unrelated S1PR1 modulators
      (ponesimod and CYM-5442) and S1PR1 antagonists (NIBR-14/15) but not S1PR1
      agonists (SEW2871). Our findings identify for the first time the S1P/S1PR1 axis
      as a promising molecular and therapeutic target in chemotherapy-induced painful
      peripheral neuropathy, establish a mechanistic insight into the biomolecular
      signaling pathways, and provide the rationale for the clinical evaluation of
      FTY720 in chronic pain patients.

PMID- 24876380
TI  - Predicting enzyme adsorption to lignin films by calculating enzyme surface
      hydrophobicity.
AB  - The inhibitory action of lignin on cellulase cocktails is a major challenge to
      the biological saccharification of plant cell wall polysaccharides. Although the
      mechanism remains unclear, hydrophobic interactions between enzymes and lignin
      are hypothesized to drive adsorption. Here we evaluate the role of hydrophobic
      interactions in enzyme-lignin binding. The hydrophobicity of the enzyme surface
      was quantified using an estimation of the clustering of nonpolar atoms,
      identifying potential interaction sites. The adsorption of enzymes to lignin
      surfaces, measured using the quartz crystal microbalance, correlates to the
      hydrophobic cluster scores. Further, these results suggest a minimum hydrophobic
      cluster size for a protein to preferentially adsorb to lignin. The impact of
      electrostatic contribution was ruled out by comparing the isoelectric point (pI)
      values to the adsorption of proteins to lignin surfaces. These results
      demonstrate the ability to predict enzyme-lignin adsorption and could potentially
      be used to design improved cellulase cocktails, thus lowering the overall cost of
      biofuel production. 

PMID- 24876381
TI  - The Fab conformations in the solution structure of human immunoglobulin G4 (IgG4)
      restrict access to its Fc region: implications for functional activity.
AB  - Human IgG4 antibody shows therapeutically useful properties compared with the
      IgG1, IgG2, and IgG3 subclasses. Thus IgG4 does not activate complement and shows
      conformational variability. These properties are attributable to its hinge
      region, which is the shortest of the four IgG subclasses. Using high throughput
      scattering methods, we studied the solution structure of wild-type IgG4(Ser(222))
      and a hinge mutant IgG4(Pro(222)) in different buffers and temperatures where the
      proline substitution suppresses the formation of half-antibody. Analytical
      ultracentrifugation showed that both IgG4 forms were principally monomeric with
      sedimentation coefficients s20,w(0) of 6.6-6.8 S. A monomer-dimer equilibrium was
      observed in heavy water buffer at low temperature. Scattering showed that the x
      ray radius of gyration Rg was unchanged with concentration in 50-250 mm NaCl
      buffers, whereas the neutron Rg values showed a concentration-dependent increase
      as the temperature decreased in heavy water buffers. The distance distribution
      curves (P(r)) revealed two peaks, M1 and M2, that shifted below 2 mg/ml to
      indicate concentration-dependent IgG4 structures in addition to IgG4 dimer
      formation at high concentration in heavy water. Constrained x-ray and neutron
      scattering modeling revealed asymmetric solution structures for IgG4(Ser(222))
      with extended hinge structures. The IgG4(Pro(222)) structure was similar. Both
      IgG4 structures showed that their Fab regions were positioned close enough to the
      Fc region to restrict C1q binding. Our new molecular models for IgG4 explain its
      inability to activate complement and clarify aspects of its stability and
      function for therapeutic applications. 

PMID- 24876382
TI  - Hypoxia-inducible lipid droplet-associated (HILPDA) is a novel peroxisome
      proliferator-activated receptor (PPAR) target involved in hepatic triglyceride
      secretion.
AB  - Peroxisome proliferator-activated receptors (PPARs) play major roles in the
      regulation of hepatic lipid metabolism through the control of numerous genes
      involved in processes such as lipid uptake and fatty acid oxidation. Here we
      identify hypoxia-inducible lipid droplet-associated (Hilpda/Hig2) as a novel PPAR
      target gene and demonstrate its involvement in hepatic lipid metabolism.
      Microarray analysis revealed that Hilpda is one of the most highly induced genes
      by the PPARalpha agonist Wy14643 in mouse precision cut liver slices. Induction
      of Hilpda mRNA by Wy14643 was confirmed in mouse and human hepatocytes. Oral
      dosing with Wy14643 similarly induced Hilpda mRNA levels in livers of wild-type
      mice but not Ppara(-/-) mice. Transactivation studies and chromatin
      immunoprecipitation showed that Hilpda is a direct PPARalpha target gene via a
      conserved PPAR response element located 1200 base pairs upstream of the
      transcription start site. Hepatic overexpression of HILPDA in mice via adeno
      associated virus led to a 4-fold increase in liver triglyceride storage, without
      any changes in key genes involved in de novo lipogenesis, beta-oxidation, or
      lipolysis. Moreover, intracellular lipase activity was not affected by HILPDA
      overexpression. Strikingly, HILPDA overexpression significantly impaired hepatic
      triglyceride secretion. Taken together, our data uncover HILPDA as a novel PPAR
      target that raises hepatic triglyceride storage via regulation of triglyceride
      secretion. 

PMID- 24876384
TI  - Robustness of the rotary catalysis mechanism of F1-ATPase.
AB  - F1-ATPase (F1) is the rotary motor protein fueled by ATP hydrolysis. Previous
      studies have suggested that three charged residues are indispensable for
      catalysis of F1 as follows: the P-loop lysine in the phosphate-binding loop,
      GXXXXGK(T/S); a glutamic acid that activates water molecules for nucleophilic
      attack on the gamma-phosphate of ATP (general base); and an arginine directly
      contacting the gamma-phosphate (arginine finger). These residues are well
      conserved among P-loop NTPases. In this study, we investigated the role of these
      charged residues in catalysis and torque generation by analyzing alanine
      substituted mutants in the single-molecule rotation assay. Surprisingly, all
      mutants continuously drove rotary motion, even though the rotational velocity was
      at least 100,000 times slower than that of wild type. Thus, although these
      charged residues contribute to highly efficient catalysis, they are not
      indispensable to chemo-mechanical energy coupling, and the rotary catalysis
      mechanism of F1 is far more robust than previously thought. 

PMID- 24876383
TI  - Conserved allosteric hot spots in the transmembrane domains of cystic fibrosis
      transmembrane conductance regulator (CFTR) channels and multidrug resistance
      protein (MRP) pumps.
AB  - ATP-binding cassette (ABC) transporters are an ancient family of transmembrane
      proteins that utilize ATPase activity to move substrates across cell membranes.
      The ABCC subfamily of the ABC transporters includes active drug exporters (the
      multidrug resistance proteins (MRPs)) and a unique ATP-gated ion channel (cystic
      fibrosis transmembrane conductance regulator (CFTR)). The CFTR channel shares
      gating principles with conventional ligand-gated ion channels, but the allosteric
      network that couples ATP binding at its nucleotide binding domains (NBDs) with
      conformational changes in its transmembrane helices (TMs) is poorly defined. It
      is also unclear whether the mechanisms that govern CFTR gating are conserved with
      the thermodynamically distinct MRPs. Here we report a new class of gain of
      function (GOF) mutation of a conserved proline at the base of the pore-lining
      TM6. Multiple substitutions of this proline promoted ATP-free CFTR activity and
      activation by the weak agonist, 5'-adenylyl-beta,gamma-imidodiphosphate (AMP
      PNP). TM6 proline mutations exhibited additive GOF effects when combined with a
      previously reported GOF mutation located in an outer collar of TMs that surrounds
      the pore-lining TMs. Each TM substitution allosterically rescued the ATP
      sensitivity of CFTR gating when introduced into an NBD mutant with defective ATP
      binding. Both classes of GOF mutations also rescued defective drug export by a
      yeast MRP (Yor1p) with ATP binding defects in its NBDs. We conclude that the
      conserved TM6 proline helps set the energy barrier to both CFTR channel opening
      and MRP-mediated drug efflux and that CFTR channels and MRP pumps utilize similar
      allosteric mechanisms for coupling conformational changes in their translocation
      pathways to ATP binding at their NBDs. 

PMID- 24876386
TI  - Mammalian COPII coat component SEC24C is required for embryonic development in
      mice.
AB  - COPII-coated vesicles mediate the transport of newly synthesized proteins from
      the endoplasmic reticulum to the Golgi. SEC24 is the COPII component primarily
      responsible for recruitment of protein cargoes into nascent vesicles. There are
      four Sec24 paralogs in mammals, with mice deficient in SEC24A, -B, and -D
      exhibiting a wide range of phenotypes. We now report the characterization of mice
      with deficiency in the fourth Sec24 paralog, SEC24C. Although mice
      haploinsufficient for Sec24c exhibit no apparent abnormalities, homozygous
      deficiency results in embryonic lethality at approximately embryonic day 7.
      Tissue-specific deletion of Sec24c in hepatocytes, pancreatic cells, smooth
      muscle cells, and intestinal epithelial cells results in phenotypically normal
      mice. Thus, SEC24C is required in early mammalian development but is dispensable
      in a number of tissues, likely as a result of compensation by other Sec24
      paralogs. The embryonic lethality resulting from loss of SEC24C occurs
      considerably later than the lethality previously observed in SEC24D deficiency;
      it is clearly distinct from the restricted neural tube phenotype of Sec24b null
      embryos and the mild hypocholesterolemic phenotype of adult Sec24a null mice.
      Taken together, these results demonstrate that the four Sec24 paralogs have
      developed unique functions over the course of vertebrate evolution.

PMID- 24876385
TI  - Cross-talk phosphorylations by protein kinase C and Pho85p-Pho80p protein kinase
      regulate Pah1p phosphatidate phosphatase abundance in Saccharomyces cerevisiae.
AB  - Yeast Pah1p is the phosphatidate phosphatase that catalyzes the penultimate step
      in triacylglycerol synthesis and plays a role in the transcriptional regulation
      of phospholipid synthesis genes. The enzyme is multiply phosphorylated, some of
      which is mediated by Pho85p-Pho80p, Cdc28p-cyclin B, and protein kinase A. Here,
      we showed that Pah1p is a bona fide substrate of protein kinase C; the
      phosphorylation reaction was time- and dose-dependent and dependent on the
      concentrations of ATP (Km = 4.5 MUm) and Pah1p (Km = 0.75 MUm). The stoichiometry
      of the reaction was 0.8 mol of phosphate/mol of Pah1p. By combining mass
      spectrometry, truncation analysis, site-directed mutagenesis, and phosphopeptide
      mapping, we identified Ser-677, Ser-769, Ser-773, and Ser-788 as major sites of
      phosphorylation. Analysis of Pah1p phosphorylations by different protein kinases
      showed that prephosphorylation with protein kinase C reduces its subsequent
      phosphorylation with protein kinase A and vice versa. Prephosphorylation with
      Pho85p-Pho80p had an inhibitory effect on its subsequent phosphorylation with
      protein kinase C; however, prephosphorylation with protein kinase C had no effect
      on the subsequent phosphorylation with Pho85p-Pho80p. Unlike its phosphorylations
      by Pho85p-Pho80p and protein kinase A, which cause a significant reduction in
      phosphatidate phosphatase activity, the phosphorylation of Pah1p by protein
      kinase C had a small stimulatory effect on the enzyme activity. Analysis of
      phosphorylation-deficient forms of Pah1p indicated that protein kinase C does not
      have a major effect on its location or its function in triacylglycerol synthesis,
      but instead, the phosphorylation favors loss of Pah1p abundance when it is not
      phosphorylated with Pho85p-Pho80p. 

PMID- 24876387
TI  - Cenp-meta is required for sustained spindle checkpoint.
AB  - Cenp-E is a kinesin-like motor protein required for efficient end-on attachment
      of kinetochores to the spindle microtubules. Cenp-E immunodepletion in Xenopus
      mitotic extracts results in the loss of mitotic arrest and massive chromosome
      missegregation, whereas its depletion in mammalian cells leads to chromosome
      segregation defects despite the presence of a functional spindle assembly
      checkpoint (SAC). Cenp-meta has previously been reported to be the Drosophila
      homolog of vertebrate Cenp-E. In this study, we show that cenp-metaDelta mutant
      neuroblasts arrest in mitosis when treated with colchicine. cenp-metaDelta mutant
      cells display a mitotic delay. Yet, despite the persistence of the two checkpoint
      proteins Mad2 and BubR1 on unattached kinetochores, these cells eventually enter
      anaphase and give rise to highly aneuploid daughter cells. Indeed, we find that
      cenp-metaDelta mutant cells display a slow but continuous degradation of cyclin
      B, which eventually triggers the mitotic exit observed. Thus, our data provide
      evidence for a role of Cenp-meta in sustaining the SAC response. 

PMID- 24876388
TI  - Ballchen is required for self-renewal of germline stem cells in Drosophila
      melanogaster.
AB  - Self-renewing stem cells are pools of undifferentiated cells, which are
      maintained in cellular niche environments by distinct tissue-specific signalling
      pathways. In Drosophila melanogaster, female germline stem cells (GSCs) are
      maintained in a somatic niche of the gonads by BMP signalling. Here we report a
      novel function of the Drosophila kinase Ballchen (BALL), showing that its cell
      autonomous role is to maintain the self-renewing capacity of female GSCs
      independent of BMP signalling. ball mutant GSCs are eliminated from the niche and
      subsequently differentiate into mature eggs, indicating that BALL is largely
      dispensable for differentiation. Similar to female GSCs, BALL is required to
      maintain self-renewal of male GSCs, suggesting a tissue independent requirement
      of BALL for self-renewal of germline stem cells. 

PMID- 24876389
TI  - Fission yeast arrestin-related trafficking adaptor, Arn1/Any1, is ubiquitinated
      by Pub1 E3 ligase and regulates endocytosis of Cat1 amino acid transporter.
AB  - The Tsc1-Tsc2 complex homologous to human tuberous sclerosis complex proteins
      governs amino acid uptake by regulating the expression and intracellular
      distribution of amino acid transporters in Schizosaccharomyces pombe. Here, we
      performed a genetic screening for molecules that are involved in amino acid
      uptake and found Arn1 (also known as Any1). Arn1 is homologous to ART1, an
      arrestin-related trafficking adaptor (ART) in Saccharomyces cerevisiae, and
      contains a conserved arrestin motif, a ubiquitination site, and two PY motifs.
      Overexpression of arn1(+) confers canavanine resistance on cells, whereas its
      disruption causes hypersensitivity to canavanine. We also show that Arn1
      regulates endocytosis of the Cat1 amino acid transporter. Furthermore, deletion
      of arn1(+) suppresses a defect of amino acid uptake and the aberrant Cat1
      localization in tsc2Delta. Arn1 interacts with and is ubiquitinated by the Pub1
      ubiquitin ligase, which is necessary to regulate Cat1 endocytosis. Cat1 undergoes
      ubiquitinations on lysine residues within the N-terminus, which are mediated, in
      part, by Arn1 to determine Cat1 localization. Correctively, Arn1 is an ART in S.
      pombe and contributes to amino acid uptake through regulating Cat1 endocytosis in
      which Tsc2 is involved. 

PMID- 24876391
TI  - Defects in the synthetic pathway prevent DIF-1 mediated stalk lineage
      specification cascade in the non-differentiating social amoeba, Acytostelium
      subglobosum.
AB  - Separation of somatic cells from germ-line cells is a crucial event for
      multicellular organisms, but how this step was achieved during evolution remains
      elusive. In Dictyostelium discoideum and many other dictyostelid species,
      solitary amoebae gather and form a multicellular fruiting body in which germ-line
      spores and somatic stalk cells differentiate, whereas in Acytostelium
      subglobosum, acellular stalks form and all aggregated amoebae become spores. In
      this study, because most D. discoideum genes known to be required for stalk cell
      differentiation have homologs in A. subglobosum, we inferred functional
      variations in these genes and examined conservation of the stalk cell
      specification cascade of D. discoideum mediated by the polyketide differentiation
      inducing factor-1 (DIF-1) in A. subglobosum. Through heterologous expression of
      A. subglobosum orthologs of DIF-1 biosynthesis genes in D. discoideum, we
      confirmed that two of the three genes were functional equivalents, while DIF
      methyltransferase (As-dmtA) involved at the final step of DIF-1 synthesis was
      not. In fact, DIF-1 activity was undetectable in A. subglobosum lysates and
      amoebae of this species were not responsive to DIF-1, suggesting a lack of DIF-1
      production in this species. On the other hand, the molecular function of an A.
      subglobosum ortholog of DIF-1 responsive transcription factor was equivalent with
      that of D. discoideum and inhibition of polyketide synthesis caused developmental
      arrest in A. subglobosum, which could not be rescued by DIF-1 addition. These
      results suggest that non-DIF-1 polyketide cascades involving downstream
      transcription factors are required for fruiting body development of A.
      subglobosum. 

PMID- 24876393
TI  - Ipilimumab-induced colonic perforation.
AB  - Biologic immune modulators such as ipilimumab have demonstrated the efficacy
      against metastatic melanoma. We present a recent case of a 52-year-old male who
      initially developed mild colitis following the initiation of ipilimumab treatment
      for metastatic melanoma. Despite initial improvement with immediate cessation of
      drug and initiation of high-dose steroid therapy his clinical condition worsened
      and the patient presented to our facility in extremis from colonic perforation.
      Following an extended right hemicolectomy his postoperative period was extended
      due to continued symptomatic enteritis. After 3 weeks colonoscopy revealed that
      the autoimmune event had begun to subside;  his condition improved, resulting in
      discharge. We discuss this particular side effect with respect to ipilimumab
      adjuvant therapy in melanoma. 

PMID- 24876390
TI  - Inward cholesterol gradient of the membrane system in P. falciparum-infected
      erythrocytes involves a dilution effect from parasite-produced lipids.
AB  - Plasmodium falciparum (Pf) infection remodels the human erythrocyte with new
      membrane systems, including a modified host erythrocyte membrane (EM), a
      parasitophorous vacuole membrane (PVM), a tubulovesicular network (TVN), and
      Maurer's clefts (MC). Here we report on the relative cholesterol contents of
      these membranes in parasitized normal (HbAA) and hemoglobin S-containing (HbAS,
      HbAS) erythrocytes. Results from fluorescence lifetime imaging microscopy (FLIM)
      experiments with a cholesterol-sensitive fluorophore show that membrane
      cholesterol levels in parasitized erythrocytes (pRBC) decrease inwardly from the
      EM, to the MC/TVN, to the PVM, and finally to the parasite membrane (PM).
      Cholesterol depletion of pRBC by methyl-beta-cyclodextrin treatment caused a
      collapse of this gradient. Lipid and cholesterol exchange data suggest that the
      cholesterol gradient involves a dilution effect from non-sterol lipids produced
      by the parasite. FLIM signals from the PVM or PM showed little or no difference
      between parasitized HbAA vs HbS-containing erythrocytes that differed in lipid
      content, suggesting that malaria parasites may regulate the cholesterol contents
      of the PVM and PM independently of levels in the host cell membrane. Cholesterol
      levels may affect raft structures and the membrane trafficking and sorting
      functions that support Pf survival in HbAA, HbAS and HbSS erythrocytes. 

PMID- 24876392
TI  - Spontaneous surgical emphysema of the larynx following hyperextension of the
      neck.
AB  - Surgical emphysema of the larynx is rare in the absence of trauma and there are a
      paucity of case reports that describe such conditions. We present what we believe
      to be an unusual, atraumatic mechanism for mucosal breech of the larynx with
      subsequent surgical emphysema. Nasendoscopy revealed oedema of the arytenoid
      cartilage and computed tomography revealed moderate subcutaneous emphysema of the
      larynx. No fracture was seen. After conservative management the patient made a
      complete recovery. 

PMID- 24876394
TI  - A painless swelling of the abdominal wall.
AB  - Case report. A man with a painless swelling of the abdominal wall. A 77-year-old
      male presented with a progressively increasing painless swelling of the abdominal
      wall due to nodular fasciitis. 

PMID- 24876395
TI  - Chylous mesenteric cysts: a rare surgical challenge.
AB  - A mesenteric cyst is defined as a cyst that is located in the mesentery of the
      gastrointestinal tract and may extend from the base of the mesentery into the
      retroperitoneum. It is often asymptomatic and therefore it is usually found as an
      incidental finding. Preoperative diagnosis may be possible with computed
      tomography and magnetic resonance imaging. However, the correct diagnosis can
      only be made with histology. The first-choice therapy is the complete removal of
      the cyst, which must be accurately planned according to the anatomy of the
      lesion, its dimensions and its relationships with major abdominal structures. We
      present two clinical cases: the one of a 30-year-old man with a mesenteric cyst
      that was removed by laparoscopy and the other of a 61-year-old woman who
      underwent open excision of a huge retroperitoneal cyst. 

PMID- 24876396
TI  - Enteropathy associated T-cell lymphoma presenting with multiple episodes of small
      bowel haemorrhage and perforation.
AB  - Enteropathy-associated T cell lymphoma (EATCL) is an intestinal neoplasm of intra
      epithelial T lymphocytes associated with coeliac disease. Although the incidence
      is rare, EATCL runs an aggressive disease course and produces multi-focal
      ulcerative lesions most commonly in the proximal small bowel. As such, patients
      may present with intestinal perforation, obstruction or haemorrhage. Management
      of EATCL requires a combination of early diagnosis and treatment by surgical
      resection followed by chemotherapy to achieve treatment success. Overall however,
      the treatment completion rate remains at 50% and EATCL carries a poor prognosis
      with a 5-year survival rate of <20%. 

PMID- 24876397
TI  - Intercalary endoprosthesis for salvage of failed intraoperative extracorporeal
      autogeneous irradiated bone grafting (IORBG) reconstruction.
AB  - Intraoperative extracorporeal autogeneous irradiated bone grafting (IORBG) after
      femoral tumor resection ultimately sometimes will fail in patients achieving long
      term survival. There are several alternative surgical approaches for revision of
      these reconstructions. In 2002 and 2005, two patients with femoral intercalary
      resection of malignant tumor (synovial sarcoma and MFH) underwent IORBG
      reconstruction with intramedullary nail or plate. At 32 and 96 months after IORBG
      reconstruction, both patients had failed IORBG (pathological fracture) in the
      femur. We used custom-made endoprostheses in these two patients to reconstruct
      femoral diaphyseal bone defect after excision of failed IORBG. Follow-up of the
      patients averaged 40.5 months (range, 39-42 months) after endoprosthetic
      revision. Musculoskeletal Tumor Society scores averaged 75% (66-83%). When used
      to salvage massive IORBG failure from fractures, intercalary endoprosthetic
      revision preserves limb function with minimal complications. 

PMID- 24876398
TI  - Discovery of a rare ileocecal plasmacytoma.
AB  - Here we report the discovery of an extramedullary ileocecal plasmacytoma, a rare
      entity reported only ~60 times in the literature. This finding occurred during
      management of a patient who had sustained an occult perforation during diagnostic
      colonoscopy. We explored the patient finding a large ileocecal perforation, and
      thus a right hemicolectomy was performed. Interestingly, the pathology of the
      mass was consistent with an extramedullary plasmacytoma, which is a very rare
      gastrointestinal diagnosis. We end by summarizing the presentation and work-up of
      extramedullary plasmacytoma. 

PMID- 24876399
TI  - Indirect inguinal hernia sac containing testis and spermatic cord in an adult
      patient with cryptorchidism.
AB  - Sliding hernias are those in which part of the sac wall is formed by a
      retroperitoneal organ and/or its mesentery protruding outside the abdominal wall
      cavity. The hernia sac may contain jejunum, ileum, vermiform appendix, Meckel's
      diverticulum, stomach, ovary, fallopian tube or urinary bladder. Our report
      features an adult case with cryptorchidism in which testis and spermatic cord
      constitute a component of the indirect inguinal hernia sac. 

PMID- 24876400
TI  - Anterior knee pain: an unusual presentation of renal cell carcinoma.
AB  - Metastasis of any kind to the patella is rare. Metastasis to the patella causing
      symptoms representing the first presentation of underlying malignancy is rarer
      still. We report the case of a previously fit and well 74-year-old male
      presenting with left anterior knee pain. The initial diagnosis was osteoarthritis
      but after continued symptoms a diagnosis of solitary patella metastasis from a
      primary renal cell carcinoma was confirmed. 

PMID- 24876401
TI  - Searching for the G spot in the urinary bladder: autoerotism and potential
      complications.
AB  - Self-insertion of foreign bodies into the urethra and urinary bladder for
      autoerotic stimulation is a rather rare urological emergency condition. We
      present a case of 41-year-old lady who self-inserted a crochet needle into the
      urethra for sexual pleasure, which was successfully retrieved during examination
      under general anaesthetic and endoscopic bladder evaluation. Foreign bodies in
      the urinary bladder are rarely encountered yet represent a urological challenge
      that requires prompt management in view of possible sequellae if left untreated. 

PMID- 24876402
TI  - A rare three part proximal ulnar shear fracture requiring innovative reduction
      and fixation in a paediatric elbow.
AB  - Fracture of the proximal ulna in children is an uncommon injury with various
      classification models. An 8-year-old boy presented to our emergency department
      with an isolated three part intra-articular fracture of his right proximal ulna
      from an extension injury sustained during skiing which has not been previously
      described in the literature. He was taken to the operating room for open
      reduction and internal fixation. Two cannulated screws positioned in a posterior
      anterior direction were used to hold the reduction. He was discharged from the
      hospital 24 h post-reduction in a complete cast. At 5 weeks follow-up, his elbow
      radiographs indicate no loss of reduction and at 4 months follow-up, he has
      regained a full range of movement at the elbow joint. The cannulated screws were
      left in situ as it did not cause him any harm. We propose that the described
      fracture pattern should be managed by open reduction and internal fixation
      (cannulated screws used to hold the reduction, position in a posterior-anterior
      direction). 

PMID- 24876403
TI  - Single incision laparoscopic surgery technique for transanal removal of rectal
      foreign body.
AB  - A foreign body in the rectum is not a very common surgical emergency case. In the
      treatment of rectal foreign bodies, the aim is to use the simplest possible
      method while protecting the integrity of the intestine. Many removal techniques
      have been described in the literature. Here we report a case in which a transanal
      technique using a single incision laparoscopic surgery port was successfully
      used. 

PMID- 24876404
TI  - A surprising cause of unilateral nasal obstruction and epistaxis: nasal septal
      schwannoma.
AB  - Schwannomas of the head and neck are the most common form of benign nerve sheath
      tumours, most commonly arising in the form of vestibular schwannomas. Schwannoma
      of the nasal cavity is an uncommon presentation of this pathology and
      specifically Schwannoma of the nasal septum is a rare presentation of this well
      understood disease process. We present the case of a 31-year-old Eastern European
      male who presented with unilateral nasal obstruction, congestion and epistaxis of
      3 months duration. After imaging and biopsy, the diagnosis of nasal septal
      schwannoma was made on histological examination. This diagnosis of a unilateral
      nasal mass in a young man provides an opportunity to discuss the varied
      presentations of schwannoma as well as to examine to possible causes of nasal and
      septal masses in this demographic. 

PMID- 24876405
TI  - p204-initiated innate antiviral response in mouse Leydig cells.
AB  - The mammalian testis is an immunoprivileged organ where local tissue-specific
      cells acquire an effective innate immune function against invading microbial
      pathogens. The present study demonstrated that mouse Leydig cells had innate
      antiviral activities in response to viral DNA challenge through p204 activation.
      The DNA sensor p204 and its signaling adaptor stimulator of interferon (IFN)
      genes (STING) were constitutively expressed in Leydig cells. Synthetic herpes
      simplex virus DNA analog (HSV60), a p204 agonist, induced the expression of type
      I IFNs and various antiviral proteins, including IFN-stimulating gene 15, 2'5'
      oligoadenylate synthetase, and Mx glutamyl transpeptidase 1, in Leydig cells. The
      HSV60-induced innate antiviral response in Leydig cells was significantly reduced
      by inhibiting p204 signaling using specific small interfering RNAs targeting p204
      and Sting. The antiviral response did not affect steroidogenesis in Leydig cells.
      These results indicated a novel mechanism underlying the testicular innate
      antiviral response. 

PMID- 24876406
TI  - Physiology of na+/h+ exchangers in the male reproductive tract: relevance for
      male fertility.
AB  - The maintenance of pH homeostasis in the male reproductive tract is kept through
      the involvement of several mechanisms, among which is included the
      transmembranous movement of H(+) ions. Na(+)-H(+) exchangers (SLC9, solute
      carrier 9 family members) are among the membrane transporters known to
      participate in intracellular and extracellular pH regulation but also have
      important roles in salt and water absorption across epithelia and in the
      regulation of cell volume. The presence of several Na(+)-H(+) exchangers has been
      reported in the male reproductive tract. Their involvement in the processes that
      ensure the correct pursuance of the spermatogenetic event and spermatozoa
      maturation has been suggested. Indeed, the formation of mature spermatozoa is
      highly dependent on the maintenance of adequate ductal luminal milieu pH and
      ionic balance. Perturbations in these processes result in reduced male
      reproductive potential and consequently male subfertility and/or infertility.
      Thus, it is imperative to understand H(+) transport dynamics in order to identify
      and counteract possible alterations associated with reduced male fertility caused
      by pathological conditions. Herein, we will discuss the expression pattern and
      physiological roles of SLC9 family members in the cells of the male reproductive
      tract as well as the molecular basis of H(+) transport and its involvement in
      male reproductive potential. 

PMID- 24876408
TI  - Enrichment of spermatogonial stem cells using side population in teleost.
AB  - Spermatogenesis originates from a small population of spermatogonial stem cells;
      this population can maintain continuous sperm production throughout the life of
      fish via self-renewal and differentiation. Despite their biological importance,
      spermatogonial stem cells are not thoroughly characterized because they are
      difficult to distinguish from their progeny cells that become committed to
      differentiation. We previously established a novel technique for germ cell
      transplantation to identify spermatogonial stem cells based on their colonizing
      activity and their ability to initiate donor-derived gametogenesis in the rainbow
      trout (Oncorhynchus mykiss). Although spermatogonial stem cells can be
      retrospectively identified after transplantation, there is currently no technique
      to prospectively enrich for or purify spermatogonial stem cells. Here, we
      describe a method for spermatogonial stem cell enrichment using a side
      population. With optimized Hoechst 33342 staining conditions, we successfully
      identified side-population cells among type A spermatogonia. Side-population
      cells were transcriptomically and morphologically distinct from non-side
      population cells. To functionally determine whether the transplantable
      spermatogonial stem cells were enriched in the side-population fraction, we
      compared the colonization activity of side-population cells with that of non-side
      population cells. Colonization efficiency was significantly higher with side
      population cells than with non-side-population cells or with total type A
      spermatogonia. In addition, side-population cells could produce billions of sperm
      in recipients. These results indicated that transplantable spermatogonial stem
      cells were enriched in the side-population fraction. This method will provide
      biological information that may advance our understanding of spermatogonial stem
      cells in teleosts. Additionally, this technique will increase the efficiency of
      germ cell transplantation used in surrogate broodstock technology. 

PMID- 24876407
TI  - Age- and species-dependent infiltration of macrophages into the testis of rats
      and mice exposed to mono-(2-Ethylhexyl) phthalate (MEHP).
AB  - The mechanism by which noninfectious testicular inflammation results in
      infertility is poorly understood. Here the infiltration of CD11b+ immunoreactive
      testicular interstitial cells (neutrophil, macrophages, dendritic cells) in
      immature (Postnatal Day [PND] 21, 28, and 35) and adult (PND 56) Fischer rats is
      described at 12, 24, and 48 h after an oral dose of 1 g/kg mono-(2-ethylhexyl)
      phthalate (MEHP), a well-described Sertoli cell toxicant. Increases of CD11b+
      cells are evident 12 h after MEHP exposure in PND 21 and 28 rats. In PND 28 rats,
      CD11b+ cells remained significantly elevated at 48 h, while in PND 21 rats, it
      returned to control levels by 24 h. The peak number of CD11b+ cells in PND 35 rat
      testis is delayed until 24 h, but remains significantly elevated at 48 h. In PND
      56 rats, no increase in CD11b+ cells occurs after MEHP exposure. In PND 21, 28,
      and 35 rats, a significant increase in monocyte chemoattractant protein-1 (MCP-1)
      by peritubular myoid cells occurs 12 h after MEHP. Interestingly, MEHP treatment
      of C57BL/6J mice did not incite an infiltration of CD11b+ cells at either PND 21
      or 28. The peak level of germ cell apoptosis observed 24 h after MEHP exposure in
      young rats is not seen in mice at any age or in PND 56 rats. Taken together,
      these findings implicate MCP-1 released by peritubular myoid cells in provoking
      the migration of CD11b+ cells into the immature rat testis early after MEHP
      exposure and point to a role for CD11b+ cells in triggering germ cell apoptosis
      in an age- and species-dependent manner. 

PMID- 24876409
TI  - Intrauterine coadministration of ERK1/2 inhibitor U0126 inhibits interferon TAU
      action in the endometrium and restores luteolytic PGF2alpha pulses in sheep.
AB  - In ruminants, prostaglandin F2 alpha (PGF2alpha) is synthesized and released in a
      pulsatile pattern from the endometrial luminal epithelial (LE) cells during the
      process of luteolysis. Interferon tau (IFNT) is a Type 1 IFN secreted by the
      trophoblast cells of the developing conceptus. IFNT acts locally on endometrial
      LE cells to inhibit pulsatile releases of PGF2alpha and thus establish an
      endocrine environment for recognition of pregnancy. Cell signaling pathways
      through which IFNT stimulates expression of multiple genes or proteins in
      endometrial LE are largely unknown. Results of the present investigation indicate
      that intrauterine administration of IFNT inhibits pulsatile release of PGF2alpha,
      while coadministration IFNT and ERK 1/2 inhibitor U0126 restores luteolytic
      PGF2alpha pulses in sheep. IFNT increases phosphorylation of ERK1/2 proteins and
      increases its interaction with PGT proteins in endometrial LE. Blockade of ERK1/2
      pathways inhibits IFNT action, decreases pERK1/2 and PGT protein interactions,
      and re-establishes the spatial expression of the oxytocin receptor protein
      completely and the estrogen receptor protein partially without modulating the
      expression of interferon regulatory factor-2 (IRF-2) protein in endometrial LE.
      IFNT does not decrease expression of COX-2, PGDH, or PGT protein in endometrial
      LE. Our results provide important new insights into IFNT signaling and the
      molecular endocrine control of PGF2alpha release at the time of establishment of
      pregnancy in ruminants. This novel IFNT-ERK1/2 signaling module needs to be
      explored in future studies to understand molecular and cellular mechanisms of
      IFNT action in endometrial LE in ruminants. 

PMID- 24876410
TI  - Cardiovascular autonomic neuropathy is associated with macrovascular risk factors
      in type 2 diabetes: new technology used for routine large-scale screening adds
      new insight.
AB  - The objective was to identify the presence of cardiovascular autonomic neuropathy
      (CAN) in a cohort of individuals with diabetes in outpatient clinics from 4
      different parts of Denmark and to explore the difference between type 1 and type
      2 diabetes in relation to CAN. The DAN-Study is a Danish multicenter study
      focusing on diabetic autonomic neuropathy. Over a period of 12 months, 382 type 1
      and 271 type 2 individuals with diabetes were tested for CAN. Patients were
      randomly recruited and tested during normal visits to outpatient clinics at 4
      Danish hospitals. The presence of CAN was quantified by performing 3
      cardiovascular reflex tests (response to standing, deep breathing, and valsalva).
      To describe possible associations, multivariate analysis with CAN as the
      dependent variable was performed. The prevalence of CAN was higher among patients
      with type 2 diabetes (35%) compared to patients with type 1 diabetes (25%).
      Multivariate analysis revealed significant associations between CAN and different
      risk markers in the 2 populations. In type 1 diabetes patients CAN was associated
      with microalbuminuria (P < .001), macroalbuminuria (P = .011), simplex
      retinopathy (P < .001), proliferative retinopathy (P < .001), and peripheral
      neuropathy (P = .041). Among type 2 diabetes patients CAN was independently
      associated with high pulse pressure (P < .01), BMI (P = .006), and smoking (P =
      .025). In this cross-sectional observational study CAN was independently
      associated with microvascular complication in type 1, whereas in type 2 CAN was
      associated with macrovascular risk factors. 

PMID- 24876411
TI  - Comparison of intensive insulin therapy using a bolus calculator in type 1 vs.
      type 2.

PMID- 24876412
TI  - A novel algorithm for prediction and detection of hypoglycemia based on
      continuous glucose monitoring and heart rate variability in patients with type 1
      diabetes.
AB  - Hypoglycemia is a common and serious side effect of insulin therapy in patients
      with diabetes. Early detection and prediction of hypoglycemia may improve
      treatment and avoidance of serious complications. Continuous glucose monitoring
      (CGM) has previously been used for detection of hypoglycemia, but with a modest
      accuracy. Therefore, our aim was to investigate whether a novel algorithm that
      adds information of the complex dynamic/pattern of heart rate variability (HRV)
      could improve the accuracy of hypoglycemia as detected by a CGM device. Data from
      10 patients with type 1 diabetes studied during insulin-induced hypoglycemia were
      obtained. Blood glucose samples were used as reference. HRV patterns and CGM data
      were combined in a mathematical prediction algorithm. Detection of hypoglycemic
      periods, performed by the algorithm, was treated as a pattern recognition problem
      and features/patterns derived from HRV and CGM prior to each blood glucose sample
      were used to decide if that particular point in time was below the hypoglycemic
      threshold of 3.9 mmol/L. A total of 903 samples were analyzed by the novel
      algorithm, which yielded a sensitivity of 79% and a specificity of 99%. The
      algorithm was able to detect 16/16 hypoglycemic events with no false positives
      and had a lead time of 22 minutes as compared to the CGM device. Detection
      accuracy and lead time were significantly improved by the novel algorithm
      compared to that of CGM alone. 

PMID- 24876413
TI  - Pilot study using mobile health to coordinate the diabetic patient,
      diabetologist, and ophthalmologist.
AB  - In the United States, more than 25 million adults have diabetes, 40% of diabetics
      have diabetic retinopathy, and diabetes is the leading cause of blindness in
      people 20 to 74 years of age. Clinical trials have shown that strict control of
      blood glucose level and other risk factors delays diabetic retinopathy onset,
      progression, and vision loss. Patients with Type 1 or Type 2 diabetes mellitus,
      access to an Apple iPhone or iPad, and no psychological or medical condition that
      would interfere with the study participated in a nonrandomized clinical trial
      using SightBookTM, a free mobile app that enables self-measurement of visual
      function and creates a password-protected web account for each patient. Sixty
      patients enrolled in the clinical trial over a 6 month period. Twenty-six
      participants were men and 34 were women, with ages from 23 to 72 years (mean 45
      +/- 15) and diabetes duration of 1.5 to 50 years (mean 15.5 +/- 11.5). Thirty
      nine (65%) patients reported Type 1 diabetes and 21 (35%) patients reported Type
      2 diabetes. Every patient established a personal web account on SightBook and
      invited participation of treating physicians; 51 (85%) patients completed the
      validated self-reported outcome assessments. Diabetologist examinations of 49
      (82%) patients demonstrated systolic hypertension (>=140 mgHg) in 20% and
      hemoglobin A1c >= 7.0% in 56%. Ophthalmology examinations of 45 patients showed
      visual acuity in the worse-seeing eye of < 20/40 in 18% and diabetic retinopathy
      in 42% of patients. This clinical trial used a mobile health app to incorporate
      diabetic patient self-measurement of vision and coordinate the diabetic patient,
      diabetologist, and ophthalmologist for control of diabetes and diabetic
      retinopathy risk factors. 

PMID- 24876414
TI  - Improving type 1 diabetes management with mobile tools: a systematic review.
AB  - This study aims to provide a better understanding of the ability of mobile health
      tools to offer glycemic control for patients with type 1 diabetes mellitus. Data
      gained from research articles searched in PubMed, Ovid (Medline), and CINAHL from
      2005 to 2013 focused on interventions introduced to a type 1 diabetic population.
      Articles were screened to identify interventions that examined mobile health
      tools effect on glycemic control using %A1C as a proxy. Fourteen articles were
      included in this study. Descriptive data, %A1C difference, and statistical
      significance, if available, were extracted for comparison. Five major categories
      were identified across the spectrum of interventions, including "Internet,"
      "Mobile," "Mobile and Internet," "Phone," and "Videoconference and phone." Seven
      of the 14 articles reported statistically significant decreases in measured
      outcomes. Seven studies examine a single cohort, and 7 examined a double cohort.
      Eleven of the 14 authors (79%) reported success with their intervention. Twelve
      studies reported a decrease in %A1C values in their intervention groups. Initial
      results for glycemic control through these tools appear promising, though
      inconclusive. Additional measures of mobile health tool efficacy should be
      assessed more directly. More rigorous study methods are also needed to improve
      the reliability of results. 

PMID- 24876415
TI  - Selective allosteric antibodies to the insulin receptor for the treatment of
      hyperglycemic and hypoglycemic disorders.
AB  - Many therapeutic monoclonal antibodies act as antagonists to receptors by
      targeting and blocking the natural ligand binding site (orthosteric site). In
      contrast, the use of antibodies to target receptors at allosteric sites (distinct
      from the orthosteric site) has not been extensively studied. This approach is
      especially important in metabolic diseases in which endogenous ligand levels are
      dysregulated. Herein, we review our investigations of 3 categories of human
      monoclonal antibodies that bind allosterically to the insulin receptor (INSR) and
      affect its activity: XMetA, XMetS and XMetD. XMetA directly activates the INSR
      either alone or in combination with insulin. XMetS, in contrast, does not
      directly activate the INSR but markedly enhances the receptor's ability to bind
      insulin and potentiate insulin signaling. Both XMetA and XMetS are effective in
      controlling hyperglycemia in mouse models of diabetes. A third allosteric
      antibody, XMetD, is an inhibitor of INSR signaling. This antibody reverses
      insulin-induced hypoglycemia in a mouse model of hyperinsulinemia. These studies
      indicate, therefore, that allosteric antibodies to INSR can modulate its
      signaling and correct conditions of glucose dysregulation. These studies also
      raise the possibility that the use of allosteric antibodies can be expanded to
      other receptors for the treatment of metabolic disorders. 

PMID- 24876416
TI  - Skin and adhesive issues with continuous glucose monitors: a sticky situation.
AB  - The purpose of this article is to describe challenges associated with successful
      use of continuous glucose monitoring (CGM) by young children with type 1 diabetes
      (T1D) and to detail the techniques and products used to improve the duration of
      sensor wear. The DirecNet Study Group conducted 2 studies in 169 children with
      T1D between the ages of 1 and 9 years who were instructed to wear a CGM device
      daily. Problems related to skin irritation and sensor adhesiveness in these young
      children presented challenges to daily use of the CGM. Study coordinators
      instituted a variety of techniques using commercially available products to
      attempt to overcome these problems. Three primary factors that contributed to
      reduced CGM use were identified: the limited body surface area in smaller
      children, ambient temperature and humidity, as well as the type and duration of
      physical activity. Using supplemental products to minimize the impact of these
      factors resulted in improved adherence and reduced skin irritation. Achieving
      satisfactory adhesion of the CGM sensor and transmitter may involve finding the
      right supplemental product or combination of products through trial and error.
      Optimizing adhesion and minimizing skin irritation can significantly improve
      duration of use and tolerability of CGM devices by young children. 

PMID- 24876417
TI  - Postprandial plasma glucose response and gastrointestinal symptom severity in
      patients with diabetic gastroparesis.
AB  - Gastroparesis is a well-known diabetic complication. The pathogenesis is not
      fully understood. However, it is important to early diagnose these patients. This
      study evaluated the plasma glucose response after a test meal, and
      gastrointestinal (GI) symptom severity in patients with clinical suspicion of
      diabetic gastroparesis, and assessed its usefulness to predict gastroparesis. In
      all, 83 subjects with insulin-treated diabetes mellitus (DM) type 1 and 2 were
      included; 53 subjects had gastroparesis and 30 had normal gastric emptying
      determined by gastric scintigraphy. GI symptom severity during the preceding 2
      weeks was evaluated with a validated questionnaire. The test meal consisted of
      100 g meat, 40 g pasta, 150 g carrot, and 5 g oil. The subjects ingested the meal
      under fasting conditions, and plasma glucose was followed during 180 minutes.
      Patients with gastroparesis demonstrated a blunted plasma glucose response after
      a test meal versus patients with normal gastric emptying (P < .005), reflected by
      lower maximum increase in plasma glucose response and incremental area under the
      curve of the plasma glucose, but a similar time to the maximum plasma glucose
      level. All GI symptoms were more severe in patients with gastroparesis. GI
      symptom severity had the best discriminative value to identify patients with
      gastroparesis with an area under the receiver operating curve of 0.83 (optimal
      cutoff: sensitivity 87%, specificity 80%). Patients with diabetic gastroparesis
      have a blunted postprandial plasma glucose response. Combining this information
      with the presence of GI symptoms can help clinicians identify diabetic patients
      with gastroparesis. 

PMID- 24876419
TI  - Improving the drug quality and safety net.
AB  - When large quantities of contaminated, subpotent, or superpotent drugs are
      introduced into the medical supply pipeline, injury or death of hundreds or
      thousands of patients can occur. Tracing the origin of substandard and dangerous
      products and tracking across regions and countries where shipped is quite costly
      in both money and time. From patients' perspective, timely access to quality
      product is paramount. Receiving deficient product threatens their survival and
      creates huge sums of financial cost to both them and the medical system. With the
      passage of HR 3204 the FDA must now find a way to be proactive in policing the
      global medical product supply line without restricting market availability.
      Without a comprehensive, world-focused implementation plan these new regulations
      will fail to protect the public. 

PMID- 24876418
TI  - Skin blood perfusion and cellular response to insertion of insulin pen needles
      with different diameters.
AB  - Today most research on pen needle design revolves around pain perception
      statements through clinical trials, but these are both costly, timely, and
      require high sample sizes. The purpose of this study was to test if tissue
      damage, caused by different types of needles, can be assessed by evaluating skin
      blood perfusion response around needle insertion sites. Three common sized pen
      needles of 28G, 30G, and 32G as well as hooked 32G needles, were inserted into
      the neck skin of pigs and then removed. Laser Speckle Contrast Analysis was used
      to measure skin blood perfusion for 20 minutes after the insertions. Seven pigs
      were included in the study and a total of 118 randomized needle insertions were
      conducted. Histology was made of tissue samples inserted with 18G, 28G, and 32G
      needles, and stained to quantify red and white blood cell response. Based on area
      under curve, calculated for each individual blood perfusion recording and grouped
      according to needle type, skin blood perfusion response relates to needle
      diameter. The response was significantly higher after insertions with 28G and
      hooked 32G needles than with 30G (P < .05) and 32G (P < .01) needles. Histology
      results were not significant, but there was a trend of an increased response with
      increasing needle diameter. Skin blood perfusion response to pen needle
      insertions rank according to needle diameter, and the tissue response caused by
      hooked 32G needles corresponds to that of 28G needles. The relation between
      needle diameter and trauma when analyzing histology was also suggested. 

PMID- 24876420
TI  - Comparison between one-point calibration and two-point calibration approaches in
      a continuous glucose monitoring algorithm.
AB  - The purpose of this study was to investigate the effect of using a 1-point
      calibration approach instead of a 2-point calibration approach on the accuracy of
      a continuous glucose monitoring (CGM) algorithm. A previously published real-time
      CGM algorithm was compared with its updated version, which used a 1-point
      calibration instead of a 2-point calibration. In addition, the contribution of
      the corrective intercept (CI) to the calibration performance was assessed.
      Finally, the sensor background current was estimated real-time and
      retrospectively. The study was performed on 132 type 1 diabetes patients.
      Replacing the 2-point calibration with the 1-point calibration improved the CGM
      accuracy, with the greatest improvement achieved in hypoglycemia (18.4% median
      absolute relative differences [MARD] in hypoglycemia for the 2-point calibration,
      and 12.1% MARD in hypoglycemia for the 1-point calibration). Using 1-point
      calibration increased the percentage of sensor readings in zone A+B of the Clarke
      error grid analysis (EGA) in the full glycemic range, and also enhanced
      hypoglycemia sensitivity. Exclusion of CI from calibration reduced hypoglycemia
      accuracy, while slightly increased euglycemia accuracy. Both real-time and
      retrospective estimation of the sensor background current suggest that the
      background current can be considered zero in the calibration of the SCGM1 sensor.
      The sensor readings calibrated with the 1-point calibration approach indicated to
      have higher accuracy than those calibrated with the 2-point calibration approach.

PMID- 24876421
TI  - Childhood diabetes in the Nordic countries: a comparison of quality registries.
AB  - In 2008 a Nordic collaboration was established between the quality registries in
      Denmark, Iceland, Norway, and Sweden to improve quality of care for children with
      diabetes. This study aimed to describe those registries and confirm that the
      registry variables are comparable. Selected variables were used to demonstrate
      outcome measurements. The organization of the registries and methodology are
      described. Cross-sectional data for patients between birth and 14.9 years with
      type 1 diabetes mellitus in 2009 (n = 6523) from 89 centers were analyzed.
      Variables were age, gender, and diabetic ketoacidosis at onset, together with
      age, gender, HbA1c, insulin regimen, and severe hypoglycemia at follow-up in
      2009. All 4 registries use a standardized registration at the onset of diabetes
      and at follow-up, conducted at the local pediatric diabetes centers. Methods for
      measuring HbA1c varied as did methods of registration for factors such as
      hypoglycemia. No differences were found between the outcomes of the clinical
      variables at onset. Significant variations were found at follow-up for mean
      HbA1c, the proportion of children with HbA1c < 57 mmol/mol (NGSP/DCCT 7.4%),
      (range 15-31%), the proportion with insulin pumps (range 34-55%), and the numbers
      with severe hypoglycemia (range 5.6-8.3/100 patient years). In this large
      unselected population from 4 Nordic countries, a high proportion did not reach
      their treatment target, indicating a need to improve the quality of pediatric
      diabetes care. International collaboration is needed to develop and harmonize
      quality indicators and offers possibilities to study large geographic
      populations, identify problems, and share knowledge. 

PMID- 24876422
TI  - Development of the Likelihood of Low Glucose (LLG) algorithm for evaluating risk
      of hypoglycemia: a new approach for using continuous glucose data to guide
      therapeutic decision making.
AB  - The objective was to develop an analysis methodology for generating diabetes
      therapy decision guidance using continuous glucose (CG) data. The novel
      Likelihood of Low Glucose (LLG) methodology, which exploits the relationship
      between glucose median, glucose variability, and hypoglycemia risk, is
      mathematically based and can be implemented in computer software. Using JDRF
      Continuous Glucose Monitoring Clinical Trial data, CG values for all participants
      were divided into 4-week periods starting at the first available sensor reading.
      The safety and sensitivity performance regarding hypoglycemia guidance
      "stoplights" were compared between the LLG method and one based on 10th
      percentile (P10) values. Examining 13 932 hypoglycemia guidance outputs, the
      safety performance of the LLG method ranged from 0.5% to 5.4% incorrect "green"
      indicators, compared with 0.9% to 6.0% for P10 value of 110 mg/dL. Guidance with
      lower P10 values yielded higher rates of incorrect indicators, such as 11.7% to
      38% at 80 mg/dL. When evaluated only for periods of higher glucose (median above
      155 mg/dL), the safety performance of the LLG method was superior to the P10
      method. Sensitivity performance of correct "red" indicators of the LLG method had
      an in sample rate of 88.3% and an out of sample rate of 59.6%, comparable with
      the P10 method up to about 80 mg/dL. To aid in therapeutic decision making, we
      developed an algorithm-supported report that graphically highlights low glucose
      risk and increased variability. When tested with clinical data, the proposed
      method demonstrated equivalent or superior safety and sensitivity performance. 

PMID- 24876423
TI  - A comparative effectiveness analysis of three continuous glucose monitors: the
      Navigator, G4 Platinum, and Enlite.
AB  - The effectiveness and safety of continuous glucose monitors (CGMs) is dependent
      on their accuracy and reliability. The objective of this study was to compare 3
      CGMs in adult and pediatric subjects with type 1 diabetes under closed-loop blood
      glucose (BG) control. Twenty-four subjects (12 adults) with type 1 diabetes each
      participated in one 48-hour closed-loop BG control experiment. Venous plasma
      glucose (PG) measurements obtained every 15 minutes (4657 values) were paired in
      time with corresponding CGM glucose (CGMG) measurements obtained from 3 CGMs
      (FreeStyle Navigator, Abbott Diabetes Care; G4 Platinum, Dexcom; Enlite,
      Medtronic) worn simultaneously by each subject. The Navigator and G4 Platinum
      (G4) had the best overall accuracy, with an aggregate mean absolute relative
      difference (MARD) of all paired points of 12.3 +/- 12.1% and 10.8 +/- 9.9%,
      respectively. Both had lower MARDs of all paired points than Enlite (17.9 +/-
      15.8%, P < .005). Very large errors (MARD > 50%) were less common with the G4
      (0.5%) than with the Enlite (4.3%, P = .0001) while the number of very large
      errors with the Navigator (1.4%) was intermediate between the G4 and Enlite (P =
      .1 and P = .06, respectively). The average MARD for experiments in adolescent
      subjects were lower than in adult subjects for the Navigator and G4, while there
      was no difference for Enlite. All 3 devices had similar reliability. A
      comprehensive head-to-head-to-head comparison of 3 CGMs revealed marked
      differences in both accuracy and precision. The Navigator and G4 were found to
      outperform the Enlite in these areas. 

PMID- 24876424
TI  - Evaluation of intravascular microdialysis for continuous blood glucose monitoring
      in hypoglycemia: an animal model.
AB  - We have previously shown that intravascular microdialysis in a central vein is an
      accurate method for continuous glucose monitoring in patients undergoing cardiac
      surgery. However, no hypoglycemia occurred in our earlier studies, prompting
      further evaluation of the accuracy of intravascular microdialysis in the
      hypoglycemic range. Thus, this animal study was performed. A porcine model was
      developed; hypoglycemia was induced using insulin injections. The pigs were
      monitored with intravascular microdialysis integrated in a triple-lumen central
      venous catheter. As reference, venous blood gas samples were taken every 5
      minutes and analyzed in a blood gas analyzer. Ethical permission for the animal
      experiments was obtained from the Stockholm Regional Ethical Committee, reference
      no N397/09. A total of 213 paired samples were obtained for analysis, and 126
      (59.2%) of these were in the hypoglycemic range (<74 mg/dl). Using Clarke error
      grid analysis, 100% of the paired samples were in region AB and 99% in region A.
      The ISO standard (ISO15197) was met. Bland-Altman analysis showed bias (mean
      difference) +/- limits of agreement was -0.18 +/- 16.2 mg/dl. No influence from
      glucose infusions was seen. The microdialysis monitoring system was found to be
      very responsive in rapid changes in blood glucose concentration. This study shows
      that intravascular microdialysis in a central vein is an accurate method for
      continuous glucose monitoring in hypoglycemia in a porcine experimental model.
      Furthermore, the system was not influenced by glucose administration and was
      found to be responsive in rapid blood glucose fluctuations. 

PMID- 24876425
TI  - Evaluation of the utility of a glycemic pattern identification system.
AB  - BACKGROUND: With the increasing prevalence of systems allowing automated, real
      time transmission of blood glucose data there is a need for pattern recognition
      techniques that can inform of deleterious patterns in glycemic control when
      people test. We evaluated the utility of pattern identification with a novel
      pattern identification system named VigilantTM and compared it to standard
      pattern identification methods in diabetes. METHOD: To characterize the
      importance of an identified pattern we evaluated the relative risk of future
      hypoglycemic and hyperglycemic events in diurnal periods following identification
      of a pattern in a data set of 536 patients with diabetes. We evaluated events 2
      days, 7 days, 30 days, and 61-90 days from pattern identification, across
      diabetes types and cohorts of glycemic control, and also compared the system to 6
      pattern identification methods consisting of deleterious event counts and
      percentages over 5-, 14-, and 30-day windows. RESULTS: Episodes of hypoglycemia,
      hyperglycemia, severe hypoglycemia, and severe hyperglycemia were 120%, 46%,
      123%, and 76% more likely after pattern identification, respectively, compared to
      periods when no pattern was identified. The system was also significantly more
      predictive of deleterious events than other pattern identification methods
      evaluated, and was persistently predictive up to 3 months after pattern
      identification. CONCLUSIONS: The system identified patterns that are
      significantly predictive of deleterious glycemic events, and more so relative to
      many pattern identification methods used in diabetes management today. Further
      study will inform how improved pattern identification can lead to improved
      glycemic control.

PMID- 24876427
TI  - Accuracy evaluation of blood glucose monitoring systems in children on overnight
      closed-loop control.
AB  - This pilot study evaluated the difference in accuracy between the Bayer
      Contour(r) Next (CN) and HemoCue(r) (HC) glucose monitoring systems in children
      with type 1 diabetes participating in overnight closed-loop studies. Subjects
      aged 10-18 years old were admitted to a clinical research center and glucose
      values were obtained every 30 minutes overnight. Glucose values were measured
      using whole blood samples for CN and HC readings and results were compared to
      Yellow Springs Instrument (YSI) reference values obtained with plasma from the
      same sample. System accuracy was compared using mean absolute relative difference
      (MARD) and International Organization for Standardization (ISO) accuracy
      standards. A total of 28 subjects were enrolled in the study. Glucose
      measurements were evaluated at 457 time points. CN performed better than HC with
      an average MARD of 3.13% compared to 10.73% for HC (P < .001). With a limited
      sample size, CN met ISO criteria (2003 and 2013) at all glucose ranges while HC
      did not. CN performed very well, and would make an excellent meter for future
      closed-loop studies outside of a research center. 

PMID- 24876426
TI  - Design and implementation of a web-based reporting and benchmarking center for
      inpatient glucometrics.
AB  - Insulin is a top source of adverse drug events in the hospital, and glycemic
      control is a focus of improvement efforts across the country. Yet, the majority
      of hospitals have no data to gauge their performance on glycemic control,
      hypoglycemia rates, or hypoglycemic management. Current tools to outsource
      glucometrics reports are limited in availability or function. Society of Hospital
      Medicine (SHM) faculty designed and implemented a web-based data and reporting
      center that calculates glucometrics on blood glucose data files securely uploaded
      by users. Unit labels, care type (critical care, non-critical care), and unit
      type (eg, medical, surgical, mixed, pediatrics) are defined on upload allowing
      for robust, flexible reporting. Reports for any date range, care type, unit type,
      or any combination of units are available on demand for review or downloading
      into a variety of file formats. Four reports with supporting graphics depict
      glycemic control, hypoglycemia, and hypoglycemia management by patient day or
      patient stay. Benchmarking and performance ranking reports are generated
      periodically for all hospitals in the database. In all, 76 hospitals have
      uploaded at least 12 months of data for non-critical care areas and 67 sites have
      uploaded critical care data. Critical care benchmarking reveals wide variability
      in performance. Some hospitals achieve top quartile performance in both glycemic
      control and hypoglycemia parameters. This new web-based glucometrics data and
      reporting tool allows hospitals to track their performance with a flexible
      reporting system, and provides them with external benchmarking. Tools like this
      help to establish standardized glucometrics and performance standards. 

PMID- 24876428
TI  - Application of PK/PD modeling and simulation to dosing regimen optimization of
      high-dose human regular U-500 insulin.
AB  - Pharmacokinetic/pharmacodynamic (PK/PD) studies of human regular U-500 insulin (U
      500R) at high doses commonly used in clinical practice (>100 units) have not been
      performed. The current analysis applied PK/PD modeling/simulation to fit the data
      and simulate single-dose and steady-state PK/PD of U-500R high-dose regimens.
      Data from 3 single-dose euglycemic clamp studies in healthy obese and normal
      weight patients, and normal-weight patients with type 1 diabetes were used to
      build the model. The model was sequential (PK inputs fed into PD component). PK
      was described using a 1-compartment model with first-order absorption and
      elimination. The model estimated separate absorption rate constants for U-500R
      and human regular U-100 insulin. The PD component used an effect compartment
      model, parameterized in terms of maximum pharmacologic effect (E(max)) and
      concentration to achieve 50% of E(max). The model described the data well. Steady
      state PK for once-daily (QD), twice-daily (BID), or thrice-daily (TID)
      administration appeared to be reached 24 hours after the first dose. At steady
      state, QD dosing showed the greatest fluctuations in PK/PD. BID dosing showed a
      gradual increase in insulin action with each dose and a fairly stable basal
      insulin effect. For TID dosing, activity was maintained throughout the dosing
      interval. PK/PD modeling/simulation of high U-500R doses supports BID or TID
      administration with an extended duration of activity relative to QD. TID dosing
      may provide slightly better full-day insulin effect. Additional PK/PD studies and
      randomized controlled trials of U-500R are needed to validate model predictions
      in patients with insulin-resistant diabetes requiring high-dose insulin.

PMID- 24876429
TI  - Characterizing normal-use temperature conditions of pumped insulin.
AB  - In this study, the temperature profiles of insulin pump reservoirs during normal
      wear conditions across multiple seasons were characterized. Thermocouples secured
      in reservoirs filled with insulin diluent were loaded in infusion pumps worn by
      volunteers. Reservoir and ambient environmental temperature data and activity
      levels were logged during the course of normal daily activities in February
      (winter), April (spring), and August (summer). Each seasonal data set comprised 7
      to 14 days of wear from 3 to 5 volunteers. Reservoir temperature profiles were
      generally higher than ambient temperatures, likely due to heat transfer from the
      wearer when the pump was placed close to the body. Temperature conditions inside
      pump reservoirs fluctuated between 25 degrees C and 37 degrees C regardless of
      seasonal variations. The average reservoir temperature remained close to 30
      degrees C across all seasons, notably lower than used in previously published
      compatibility and stability protocols (37 degrees C). Results from this study
      could be utilized to develop more accurate stability and compatibility testing
      procedures for new insulin formulations and/or delivery devices. 

PMID- 24876430
TI  - A study of patient experience using a blood glucose meter with an in-built
      insulin dose calculator.
AB  - Accurate calculation and adjustment of insulin doses is integral to maintaining
      glycemic control in insulin treated patients. Difficulties with insulin dose
      calculations may lead to poor adherence to blood glucose monitoring and insulin
      treatment regimes, resulting in poor metabolic control. The main objective of
      this study was to evaluate ease of use and user preference of a high
      specification touch screen blood glucose meter, which has an in-built insulin
      calculator, compared to patients' usual method of testing blood glucose and
      deciding insulin doses. Patients with diabetes on a multiple daily injection
      insulin regime used the Test Meter without the insulin calculator and 1 of 3
      comparator meters, each for a 7-day period. They then used the Test Meter with
      the in-built calculator for 10 days. Patients completed an ease of use
      questionnaire after each 7-day period, a preference questionnaire after the
      second 7-day period, and a questionnaire comparing the Test Meter with their
      usual method after the final 10-day period. Of 164 patients who completed the
      study, 76% stated a preference for the Test Meter as a diabetes management tool
      compared to their usual method. A small number of patients preferred familiar
      methods and/or calculating insulin doses themselves. The log book function of
      meters was important to most patients. The Test Meter system with in-built
      insulin calculator supports people to better manage their diabetes and increases
      their confidence. Patients have different needs and preferences which should be
      acknowledged and supported in a patient centered health service. 

PMID- 24876431
TI  - Use of the DISST model to estimate the HOMA and Matsuda indexes using only a
      basal insulin assay.
AB  - It is hypothesized that early detection of reduced insulin sensitivity (SI) could
      prompt intervention that may reduce the considerable financial strain type 2
      diabetes mellitus (T2DM) places on global health care. Reduction of the cost of
      already inexpensive SI metrics such as the Matsuda and HOMA indexes would enable
      more widespread, economically feasible use of these metrics for screening. The
      goal of this research was to determine a means of reducing the number of insulin
      samples and therefore the cost required to provide an accurate Matsuda Index
      value. The Dynamic Insulin Sensitivity and Secretion Test (DISST) model was used
      with the glucose and basal insulin measurements from an Oral Glucose Tolerance
      Test (OGTT) to predict patient insulin responses. The insulin response to the
      OGTT was determined via population based regression analysis that incorporated
      the 60-minute glucose and basal insulin values. The proposed method derived
      accurate and precise Matsuda Indices as compared to the fully sampled Matsuda (R
      = .95) using only the basal assay insulin-level data and 4 glucose measurements.
      Using a model employing the basal insulin also allows for determination of the 1
      day HOMA value. The DISST model was successfully modified to allow for the
      accurate prediction an individual's insulin response to the OGTT. In turn, this
      enabled highly accurate and precise estimation of a Matsuda Index using only the
      glucose and basal insulin assays. As insulin assays account for the majority of
      the cost of the Matsuda Index, this model offers a significant reduction in assay
      cost. 

PMID- 24876432
TI  - Clinical evaluation of a novel on-strip calibration method for blood glucose
      measurement.
AB  - This study evaluated a novel technology for improving accuracy of self-monitoring
      of blood glucose (SMBG). The technology calibrates each and every test by
      measuring the response from a predetermined amount of glucose present in the
      sample chamber of each test strip. SMBG test strips were modified to include a
      lid coated with a fast dissolving formulation containing glucose. These test
      strips were characterized for hematocrit (Hct) and temperature induced error
      response to develop a calibration algorithm. The modified test strips were used
      in a clinical evaluation involving fingerstick blood samples from 160 subjects.
      Experiments involving Hct and temperature induced errors show that the technology
      generates a signal characteristic of the error conditions in any particular test,
      but independent of glucose concentration, allowing a correction algorithm to be
      derived. The approach substantially reduced Hct and temperature derived errors.
      Clinical evaluation using fingerstick blood directly applied to prototype strips
      showed the error (measured as MARD) was reduced from 11.1 to 5.9% by the on-strip
      correction approach and the number of outliers reduced by approximately 90%. This
      technology could improve the accuracy and precision of glucose monitoring systems
      and so reduce decision errors particularly in clinical situations where
      hematocrit and temperature may be significant confounders. 

PMID- 24876433
TI  - Predictors of insulin initiation in metformin and sulfonylurea users in primary
      care practices: the role of kidney function.
AB  - The aims were to investigate predictors of insulin initiation in new users of
      metformin or sulfonylureas in primary care practices, in particular, its
      association with decreased renal function. Data from 9103 new metformin and 1120
      sulfonylurea users with normal baseline glomerular filtration rate (eGFR) >90
      ml/min/1.73 m(2) from 1072 practices were retrospectively analyzed (Disease
      Analyzer Germany: 01/2003-06/2012). Cox regression models and propensity score
      matching was used to adjust for confounders (age, sex, practice characteristics,
      comorbidity). Insulin treatment was started in 394 (4.3%) metformin and in 162
      (14.5%) sulfonylurea users within 6 years (P < .001). Kaplan-Meier curves
      (propensity score matched patients) showed that the metformin group was at a
      lower risk of insulin initiation compared to sulfonylurea users throughout the
      study period. A substantial eGFR decline (category: 15-<30 ml/min/1.73 m(2)) was
      significantly associated with a higher likelihood to have insulin initiated
      (adjusted hazard ratio [HR]: 2.39; 95% CI: 1.09-5.23) in metformin but not in
      sulfonylurea (HR: 0.45; 95% CI: 0.16-1.30) users. New users of sulfonylurea
      monotherapy in primary care practices in Germany were about 3-fold more likely to
      start insulin therapy than those with metformin. Kidney function decline was
      associated with earlier insulin initiation in metformin but not in sulfonylurea
      users. 

PMID- 24876434
TI  - Studying pancreatic risks caused by incretin-based therapies: is it a game? It's
      not a game!
AB  - A manuscript published recently on histological changes induced in the pancreas
      by incretin-based medications has been widely criticized because of ill-matched
      groups treated with incretin-based versus non-incretin-based medications and
      because of methodological problems identifying glucagon-producing cells. Now a
      study making use of the same tissue bank is available, and does not easily
      confirm the bulk of findings originally reported. This is an important
      opportunity to discuss the responsibility of authors to publish results
      potentially reproducible by other scientists as an important quality criterion,
      and the responsibility of reviewers and editors in handling such manuscripts. The
      main conclusion is that attempts to reproduce controversial findings are a
      necessity if finally the essence of novel results is at stake. 

PMID- 24876435
TI  - Help! Someone is beeping...

PMID- 24876436
TI  - Bolus calculators.
AB  - Matching meal insulin to carbohydrate intake, blood glucose, and activity level
      is recommended in type 1 diabetes management. Calculating an appropriate insulin
      bolus size several times per day is, however, challenging and resource demanding.
      Accordingly, there is a need for bolus calculators to support patients in insulin
      treatment decisions. Currently, bolus calculators are available integrated in
      insulin pumps, as stand-alone devices and in the form of software applications
      that can be downloaded to, for example, smartphones. Functionality and complexity
      of bolus calculators vary greatly, and the few handfuls of published bolus
      calculator studies are heterogeneous with regard to study design, intervention,
      duration, and outcome measures. Furthermore, many factors unrelated to the
      specific device affect outcomes from bolus calculator use and therefore bolus
      calculator study comparisons should be conducted cautiously. Despite these
      reservations, there seems to be increasing evidence that bolus calculators may
      improve glycemic control and treatment satisfaction in patients who use the
      devices actively and as intended. 

PMID- 24876437
TI  - Continuous glucose monitoring and trend accuracy: news about a trend compass.
AB  - Continuous glucose monitoring (CGM) devices are being increasingly used to
      monitor glycemia in people with diabetes. One advantage with CGM is the ability
      to monitor the trend of sensor glucose (SG) over time. However, there are few
      metrics available for assessing the trend accuracy of CGM devices. The aim of
      this study was to develop an easy to interpret tool for assessing trend accuracy
      of CGM data. SG data from CGM were compared to hourly blood glucose (BG)
      measurements and trend accuracy was quantified using the dot product. Trend
      accuracy results are displayed on the Trend Compass, which depicts trend accuracy
      as a function of BG. A trend performance table and Trend Index (TI) metric are
      also proposed. The Trend Compass was tested using simulated CGM data with varying
      levels of error and variability, as well as real clinical CGM data. The results
      show that the Trend Compass is an effective tool for differentiating good trend
      accuracy from poor trend accuracy, independent of glycemic variability.
      Furthermore, the real clinical data show that the Trend Compass assesses trend
      accuracy independent of point bias error. Finally, the importance of assessing
      trend accuracy as a function of BG level is highlighted in a case example of low
      and falling BG data, with corresponding rising SG data. This study developed a
      simple to use tool for quantifying trend accuracy. The resulting trend accuracy
      is easily interpreted on the Trend Compass plot, and if required, performance
      table and TI metric. 

PMID- 24876438
TI  - Autonomy of patients with type 2 diabetes with an insulin pump device: is it
      predictable?
AB  - BACKGROUND: Insulin pump therapy may be offered to patients with type 2 diabetes
      that is not controlled by multiple daily injections. Patients with type 2
      diabetes may suffer from unrecognized cognitive disabilities, which may
      compromise the use of a pump device. METHODS: To predict patient autonomy, we
      evaluated 39 patients with type 2 diabetes from our database (n = 143) after
      continuous subcutaneous insulin infusion (CSII) initiation using (1) an autonomy
      questionnaire evaluating the patient's cognitive and operative capacities for
      CSII utilization, (2) the Montreal Cognitive Assessment (MOCA) for the detection
      of mild cognitive disabilities, (3) the Hospital Anxiety and Depression Scale
      (HADS) for the detection of anxiety and depression, and (4) the Diabetes
      Treatment Satisfaction Questionnaire (DTSQ). Patients were selected to constitute
      3 groups matched for age, with different degrees of autonomy at discharge after
      the initial training program: complete (n = 13), partial (n = 13), or no autonomy
      (n = 13). RESULTS: The satisfaction level with the pump device was high. At the
      last follow-up visit, only 23% of patients did not reach complete autonomy. The
      autonomy score correlated fairly with the MOCA score (R = 0.771, P < .001). A
      receiver operating characteristic (ROC) analysis showed that at a cut-off score
      of 24, the MOCA identified autonomous versus dependent patients at long-term
      follow-up (area under the ROC curve [AUC], 0.893; sensitivity, 81%; specificity,
      81%). The HADS correlated negatively with the autonomy score, and the
      sociocultural level also influenced autonomy with pump utilization. CONCLUSION:
      Patients with type 2 diabetes with partial autonomy at discharge may progress to
      complete autonomy. The MOCA and HADS may help predict a patient's ability to
      manage with a pump device.

PMID- 24876439
TI  - A clinical evaluation of routine blood sampling practices in patients with
      diabetes: impact on fingerstick blood volume and pain.
AB  - BACKGROUND: There is a perception that patients with diabetes struggle to produce
      sufficient blood to fill glucose test strips, including strips with 1-uL fill
      requirements. The purpose of this study was to determine the volume of blood
      expressed when these patients perform routine fingersticks using their own
      lancing device and sampling technique and to evaluate the relationship between
      blood volume and pain. METHODS: Sixty-four patients (type 1 or type 2 diabetes)
      performed 8 fingersticks using their own lancing device and preferred depth
      setting and lancing technique. Eight different commercially available lancing
      systems were used (8 patients/system). Blood volume and perceived pain were
      recorded after each fingerstick. RESULTS: The mean blood volume across all
      patients was 3.1 uL (512 fingersticks), with 97% of patients expressing a mean of
      >=1.0 uL of blood. There was no correlation between pain response and the volume
      of blood expressed. Nearly all patients agreed that they could easily and
      comfortably obtain a 1-uL blood sample, and most patients actually preferred a
      larger drop size to ease sampling and avoid wasting strips. CONCLUSION: These
      results provide evidence across 8 lancing systems that challenge the current
      perceptions that patients with diabetes struggle to produce sufficient blood
      samples to fill most test strips, including those with 1-uL fill requirements,
      and that obtaining larger volumes of blood is more painful. These results are
      consistent with the previous literature suggesting that patients derive no real
      benefits from very low strip volumes and generally prefer a blood drop size that
      enables them to confidently fill their test strip.

PMID- 24876440
TI  - Glucose control in the ICU: is there a time for more ambitious targets again?
AB  - During the last 2 decades, the treatment of hyperglycemia in critically ill
      patients has become one of the most discussed topics in the intensive medicine
      field. The initial data suggesting significant benefit of normalization of blood
      glucose levels in critically ill patients using intensive intravenous insulin
      therapy have been challenged or even neglected by some later studies. At the
      moment, the need for glucose control in critically ill patients is generally
      accepted yet the target glucose values are still the subject of ongoing debates.
      In this review, we summarize the current data on the benefits and risks of tight
      glucose control in critically ill patients focusing on the novel technological
      approaches including continuous glucose monitoring and its combination with
      computer-based algorithms that might help to overcome some of the hurdles of
      tight glucose control. Since increased risk of hypoglycemia appears to be the
      major obstacle of tight glucose control, we try to put forward novel approaches
      that may help to achieve optimal glucose control with low risk of hypoglycemia.
      If such approaches can be implemented in real-world practice the entire concept
      of tight glucose control may need to be revisited. 

PMID- 24876441
TI  - Practical experience with a new prefilled pen device for a long-acting insulin
      analog in Japan.

PMID- 24876444
TI  - EASD diabetes technology meeting: medical associations are on track.
AB  - The first diabetes technology meeting organized by the European Diabetes
      Association covers the range from regulatory aspects, patient safety, about
      registries to clinical studies. After an intensive discussion about the evidence
      required for registration and reimbursement on new medical devices and in vitro
      diagnostics it becomes clear that more and better clinical trials will be
      required in the future. This was also highlighted by representatives of the
      American Diabetes Association. The 2 associations will be active in this field of
      research by a joint committee. This meeting is intended not to become a large
      scale meeting focused on education but to provide a platform for an open
      discussion of experts involved in all areas that are relevant to achieve a
      meaningful usage of diabetes technology. 

PMID- 24876443
TI  - Effect of algorithm aggressiveness on the performance of the Hypoglycemia
      Hyperglycemia Minimizer (HHM) System.
AB  - The Hypoglycemia-Hyperglycemia Minimizer (HHM) System aims to mitigate glucose
      excursions by preemptively modulating insulin delivery based on continuous
      glucose monitor (CGM) measurements. The "aggressiveness factor" is a key
      parameter in the HHM System algorithm, affecting how readily the system adjusts
      insulin infusion in response to changing CGM levels. Twenty adults with type 1
      diabetes were studied in closed-loop in a clinical research center for
      approximately 26 hours. This analysis focused on the effect of the aggressiveness
      factor on the insulin dosing characteristics of the algorithm and, to a lesser
      extent, on the glucose control results observed. As the aggressiveness factor
      increased from conservative to medium to aggressive: the maximum observed insulin
      dose delivered by the algorithm-which is designed to give doses that are
      corrective in nature every 5 minutes-increased (1.00 vs 1.15 vs 2.20 U,
      respectively); tendency to adhere to the subject's nominal basal dose decreased
      (61.9% vs 56.6% vs 53.4%); and readiness to decrease insulin below basal also
      increased (18.4% vs 19.4% vs 25.2%). Glucose analyses by both CGM and Yellow
      Springs Instruments (YSI) indicated that the aggressive setting of the algorithm
      resulted in the least time spent at levels >180 mg/dL, and the most time spent
      between 70-180 mg/dL. There was no severe hyperglycemia, diabetic ketoacidosis,
      or severe hypoglycemia for any of the aggressiveness values investigated. These
      analyses underscore the importance of investigating the sensitivity of the HHM
      System to its key parameters, such as the aggressiveness factor, to guide future
      development decisions.

PMID- 24876442
TI  - The role of self-monitoring of blood glucose in patients treated with SGLT-2
      inhibitors: a European expert recommendation.
AB  - The role for the novel treatment approach of sodium-glucose cotransporter-2 (SGLT
      2) in type 2 diabetes is increasing. Structured self-monitoring of blood glucose
      (SMBG), based on a less intensive and a more intensive scheme, may contribute to
      an optimization of SGLT-2 inhibitor based treatment. The current expert
      recommendation suggests individualized approaches of SMBG, using simple and
      clinically applicable schemes. Potential benefits of SMBG in SGLT-2 inhibitor
      based treatment approaches are early assessment of treatment success or failure,
      timely modification of treatment, detection of hypoglycemic episodes, assessment
      of glucose excursions, and support of diabetes management and education. The
      length and frequency of SMBG should depend on the clinical setting and the
      quality of metabolic control. 

PMID- 24876445
TI  - A heads-up display for diabetic limb salvage surgery: a view through the google
      looking glass.
AB  - Although the use of augmented reality has been well described over the past
      several years, available devices suffer from high cost, an uncomfortable form
      factor, suboptimal battery life, and lack an app-based developer ecosystem. This
      article describes the potential use of a novel, consumer-based, wearable device
      to assist surgeons in real time during limb preservation surgery and clinical
      consultation. Using routine intraoperative, clinical, and educational case
      examples, we describe the use of a wearable augmented reality device (Google
      Glass; Google, Mountain View, CA). The device facilitated hands-free, rapid
      communication, documentation, and consultation. An eyeglass-mounted screen form
      factor has the potential to improve communication, safety, and efficiency of
      intraoperative and clinical care. We believe this represents a natural
      progression toward union of medical devices with consumer technology. 

PMID- 24876446
TI  - Glucometrics of diabetic patients admitted to intensive care unit in hospitals
      with limited information technology support: is it possible?

PMID- 24876447
TI  - Accuracy assessment of two novel systems for self-monitoring of blood glucose
      following ISO 15197:2013.

PMID- 24876448
TI  - Accuracy of a novel noninvasive transdermal continuous glucose monitor in
      critically ill patients.
AB  - Stress hyperglycemia and hypoglycemia are associated with increased morbidity and
      mortality in the critically ill. Intermittent, random blood glucose (BG)
      measurements can miss episodes of hyper- and hypoglycemia. The purpose of this
      study was to determine the accuracy of the Symphony(r) continuous glucose monitor
      (CGM) in critically ill cardiac surgery patients. Fifteen adult cardiac surgery
      patients were evaluated immediately postoperatively in the intensive care unit.
      Prelude(r) SkinPrep prepared the skin and a sensor was applied to 2 test sites on
      each subject to monitor interstitial fluid glucose. Reference BG was sampled at
      30- to 60-minute intervals. The skin at the test sites was inspected for adverse
      effects. Accuracy of the retrospectively analyzed CGM data relative to reference
      BG values was determined using continuous glucose-error grid analysis (CG-EGA)
      and mean absolute relative difference (MARD). Using 570 Symphony CGM glucose
      readings paired with reference BG measurements, CG-EGA showed that 99.6% of the
      readings were within zones A and B. BG measurements ranged from 73 to 251 mg/dL.
      The MARD was 12.3%. No adverse device effects were reported. The Symphony CGM
      system is able to safely, continuously, and noninvasively monitor glucose in the
      transdermal interstitial fluid of cardiac surgery intensive care unit patients
      with accuracy similar to that reported with other CGM systems. Future versions of
      the system will need real-time data analysis, fast warm-up, and less frequent
      calibrations to be used in the clinical setting. 

PMID- 24876449
TI  - Effect of whole body vibration on skin blood flow and nitric oxide production.
AB  - BACKGROUND: Vascular dysfunction due to hyperglycemia in individuals with
      diabetes is a factor contributing to distal symmetric polyneuropathy (DSPN).
      Reactive oxygen species reduce the bioavailability of nitric oxide (NO), a
      powerful vasodilator, resulting in reduced circulation and nerve ischemia.
      Increases in blood NO concentrations and circulation have been attributed to
      whole body vibration (WBV). The purpose of this study was to the determine the
      effects of low-frequency, low-amplitude WBV on whole blood NO concentrations and
      skin blood flow (SBF) in individuals with symptoms of DSPN. METHODS: Ten patients
      with diabetes and impaired sensory perception in the lower limbs participated in
      this crossover study. Each submitted to 2 treatment conditions, WBV and sham,
      with a 1-week washout period between. Blood draws for NO analysis and laser
      Doppler imager scans of SBF were performed before, immediately after, and
      following a 5-minute recovery of each of the treatments. RESULTS: Low-frequency,
      low-amplitude WBV significantly increased SBF compared to the sham condition
      (F(2,18) = 5.82, P = .0115). Whole blood NO concentrations did not differ between
      the WBV and sham conditions immediately or 5 minutes after treatment (F(2,18) =
      1.88, P = .1813). CONCLUSIONS: These findings demonstrate that patients with
      diabetes respond to WBV with increased SBF compared to the sham condition. The
      implication is that WBV is a potential nonpharmacological therapy for
      neurovascular complications of diabetes.

PMID- 24876450
TI  - A detailed description of the implementation of inpatient insulin orders with a
      commercial electronic health record system.
AB  - In the setting of Meaningful Use laws and professional society guidelines,
      hospitals are rapidly implementing electronic glycemic management order sets.
      There are a number of best practices established in the literature for glycemic
      management protocols and programs. We believe that this is the first published
      account of the detailed steps to be taken to design, implement, and optimize
      glycemic management protocols in a commercial computerized provider order entry
      (CPOE) system. Prior to CPOE implementation, our hospital already had a mature
      glycemic management program. To transition to CPOE, we underwent the following 4
      steps: (1) preparation and requirements gathering, (2) design and build, (3)
      implementation and dissemination, and (4) optimization. These steps required more
      than 2 years of coordinated work between physicians, nurses, pharmacists, and
      programmers. With the move to CPOE, our complex glycemic management order sets
      were successfully implemented without any significant interruptions in care. With
      feedback from users, we have continued to refine the order sets, and this remains
      an ongoing process. Successful implementation of glycemic management protocols in
      CPOE is dependent on broad stakeholder input and buy-in. When using a commercial
      CPOE system, there may be limitations of the system, necessitating workarounds.
      There should be an upfront plan to apply resources for continuous process
      improvement and optimization after implementation. 

PMID- 24876451
TI  - A novel hierarchal-based approach to measure insulin sensitivity and secretion in
      at-risk populations.
AB  - The pathogenesis of type 2 diabetes is characterized by insulin resistance and
      insulin secretory dysfunction. Few existing metabolic tests measure both
      characteristics, and no such tests are inexpensive enough to enable widespread
      use. A hierarchical approach uses 2 down-sampled tests in the dynamic insulin
      sensitivity and secretion test (DISST) family to first determine insulin
      sensitivity (SI) using 4 glucose measurements. Second the insulin secretion is
      determined for only participants with reduced SI using 3 C-peptide measurements
      from the original test. The hierarchical approach is assessed via its ability to
      classify 214 individual test responses of 71 females with an elevated risk of
      type 2 diabetes into 5 bins with equivalence to the fully sampled DISST. Using an
      arbitrary SI cut-off, 102 test responses were reassayed for C-peptide and unique
      insulin secretion characteristics estimated. The hierarchical approach correctly
      classified 84.5% of the test responses and 94.4% of the responses of individuals
      with increased fasting glucose. The hierarchical approach is a low-cost
      methodology for measuring key characteristics of type 2 diabetes. Thus the
      approach could provide an economical approach to studying the pathogenesis of
      type 2 diabetes, or in early risk screening. As the higher cost test uses the
      same clinical protocol as the low-cost test, the cost of the additional
      information is limited to the assay cost of C-peptide, and no additional
      procedures or callbacks are required. 

PMID- 24876452
TI  - The effect of using a shared electronic health record on quality of care in
      people with type 2 diabetes.

PMID- 24876453
TI  - Glycemic variability in nondiabetic morbidly obese persons: results of an
      observational study and review of the literature.
AB  - Glycemic variability (GV) is correlated with oxidative stress which may lead to
      increased cardiovascular risk and poor clinical outcomes in people with
      prediabetes and diabetes. We sought to understand whether morbidly obese persons
      without diabetes by standard criteria have dysglycemia as measured by GV. We
      performed an observational study of GV metrics and carotid intima media thickness
      (CIMT) in 21 morbidly obese normoglycemic and 15 morbidly obese prediabetic
      applicants to The Biggest Loser television show. The results were compared to
      previously published studies in normoglycemic nonobese and obese individuals.
      Glucose was measured with a masked continuous glucose monitor (CGM) over 3 to 8
      days and carotid intima media thickness (CIMT) was determined by ultrasound. CGM
      derived GV metrics for GV were coefficient of variation (CV), standard deviation
      (SD), mean amplitude of glycemic excursions (MAGE), continuous overall net
      glycemic action-1 hour (CONGA1), and mean of daily differences (MODD). We found
      that morbidly obese subjects (n = 21) who were normoglycemic by standard criteria
      had higher GV (CV = 22%, SD = 24.2 mg/dl and MAGE = 48.6 mg/dl) than previous
      reports of normoglycemic, nonobese individuals (CV = 12-18%, SD = 11.5-15.0
      mg/dl, and MAGE = 26.3-28.3 mg/dl). Morbidly obese prediabetic subjects (n = 15)
      had GV metrics indistinguishable from those morbidly obese subjects who were
      normoglycemic. CIMT was higher in both morbidly obese groups compared with
      historical age- and sex-matched controls. Normoglycemic and prediabetic morbidly
      obese individuals have higher GV compared with normal weight, nondiabetic
      individuals. We speculate that this may increase the risk for macrovascular
      disease through excessive oxidative stress. 

PMID- 24876454
TI  - Cross-sectional survey and retrospective analysis of a large cohort of adults
      with type 1 diabetes with long-term continuous subcutaneous insulin infusion
      treatment.
AB  - Background. Continuous subcutaneous insulin infusion (CSII) is an established
      modality for intensive insulin treatment of type 1 diabetes (T1D), but long-term
      data concerning satisfaction, CSII function use, safety, and efficacy in real
      life conditions are scarce. Methods. We analyzed a cohort of adult patients with
      T1D treated with CSII for more than 1 year in a single diabetes center. We
      performed a cross-sectional survey in 2010 (tolerance/satisfaction and behavior
      forms) and a retrospective analysis of medical records (including HbA1c level,
      hospitalization, and catheter infections). The primary objective was to assess
      long-term tolerance/satisfaction, and secondary objectives were safety and
      efficacy. Results. There were 295 patients analyzed. After a median duration of
      CSII use of 5 years, overall satisfaction was high for about 90% of patients.
      Mean CSII-related discomfort scores were low for work, recreation, and sleep and
      moderate for sport and sexual activity (2.5 +/- 1.9, 2.6 +/- 1.8, 2.6 +/- 2.1,
      3.4 +/- 2.3, and 4.0 +/- 2.9 of 10, respectively). Despite a high level of
      diabetes education, only one third of patients were using advanced CSII
      functions. During long-term follow-up, the safety of CSII treatment was good; the
      hospitalization rate was 0.18 patients/year, and catheter infections were scarce.
      The HbA1c level dropped about -0.5% independently from CSII duration (P < .05).
      Conclusions. In this adult cohort, satisfaction and tolerance, together with
      safety, of CSII were maintained at long-term follow up. The sole basic functions
      of CSII were currently used by patients. A 0.5% decrease in the HbA1c level was
      maintained during the study period. 

PMID- 24876455
TI  - Real-world assessment of glycemic control after V-Go(r) initiation in an
      endocrine practice in the southeastern United States.

PMID- 24876456
TI  - Authors' response: evaluation of choroidal thickness among patients with
      oculocutaneous albinism.

PMID- 24876457
TI  - Managing antiplatelet and anticoagulant drugs in patients undergoing elective
      ophthalmic surgery. Authors' response.

PMID- 24876458
TI  - Acute cholecystitis presenting with massive intra-abdominal haemorrhage.
AB  - Haemorrhagic cholecystitis is a known rare life-threatening complication of acute
      cholecystitis. In this case report, we describe clinical presentation and
      radiological findings of acute cholecystitis presenting with massive intra
      abdominal haemorrhage. We present a case of a 57-year-old male presenting to the
      emergency department with clinical symptoms of acute cholecystitis. Initially,
      the patient was haemodynamically stable. Gallbladder could not be visualized by
      ultrasound. Computed tomography with IV contrast showed a large haematoma in the
      gallbladder fossa, with active extravasation of IV contrast. On angiography the
      bleeding was localized to a branch of the cystic artery, which was embolized
      using gelfoam material. The patient was taken to the operating room for an urgent
      laparotomy and cholecystectomy. 

PMID- 24876460
TI  - Surgical clip migration following laparoscopic cholecystectomy as a cause of
      cholangitis.
AB  - Gallstone disease is a common surgical presentation, and laparoscopic
      cholecystectomy is the favoured method of surgical management. Ligation of the
      cystic duct is usually performed with surgical clips, which have the potential to
      migrate into the common bile duct with time. This paper describes a case of
      cholangitis secondary to clip migration in a 42-year-old male patient 9 years
      after the initial laparoscopic cholecystectomy. Magnetic resonance
      cholangiopancreaography imaging revealed a surgical clip lodged in dilated common
      bile duct. The patient was managed successfully by endoscopic retrograde
      cholangiopancreatography. 

PMID- 24876459
TI  - Bascule caecal volvulus: a rare cause of intestinal obstruction.
AB  - Caecal volvulus is a rare cause of intestinal obstruction, with the bascule
      subtype accounting for <10% of all cases of caecal volvulus. It is associated
      with significant morbidity and mortality if left undiagnosed. We present the case
      of a 58-year-old female who presented to our surgical department with symptoms of
      intestinal obstruction. She had various radiological investigations, which
      supported the diagnosis of a caecal volvulus of the bascule subtype. She was
      subsequently managed surgically and had a right hemicolectomy and ileocolic
      anastomosis. Her recovery was uneventful and she was discharged within 1 week of
      having her operation. Fortunately, caecal volvulus of the bascule subtype is
      rarely encountered; however, clinicians need to be aware of its presentation and
      subsequent management options so that clinical outcomes are improved. 

PMID- 24876462
TI  - Bowel hath no fury like a gallbladder inflamed.
AB  - Gallstone ileus is a well-established phenomenon in which a large gallstone leads
      to mechanical small bowel obstruction. This case, however, reports the novel
      finding of a patient presenting with suprapubic pain and guarding caused by
      paralytic ileus of the small bowel and a duodenal perforation secondary to a
      necrotic gallbladder. It highlights the importance of distinguishing between
      gallstone ileus and paralytic ileus and how the management of the two conditions
      differs. Furthermore, this article discusses how paralytic ileus caused by intra
      abdominal inflammatory conditions such as cholecystitis can mask the typical
      clinical findings making the diagnosis difficult. 

PMID- 24876461
TI  - Emphysematous cholecystitis successfully treated by laparoscopic surgery.
AB  - Emphysematous cholecystitis (EC) is an uncommon variant of acute cholecystitis,
      which is caused by secondary infection of the gallbladder wall with gas-forming
      organisms. The mortality rate of EC is still as high as 25%. Emergency surgical
      intervention is indicated. Open cholecystectomy has been traditionally accepted
      as a standard treatment for EC. We present a case of EC successfully treated by
      laparoscopic surgery. Laparoscopic cholecystectomy for EC is considered to be
      safe and effective when indicated. 

PMID- 24876463
TI  - Fixation failure in an isolated tibial eminence ACL traction avulsion fracture in
      a paratrooper: is there an association with vitamin D deficiency?
AB  - Tibial eminence avulsion fracture at the ACL footprint may be caused by high
      energy forces such as a fall, in which the ACL ligament proves stronger than the
      forces that hold the bone together. For reasons of bone maturity however, tibial
      spine avulsion fractures where the ACL remains intact, typically occur in
      children but are rare in adults. This case demonstrates a rare type of adult
      tibial avulsion fracture with intact ACL and subsequent fragment fixation failure
      in which vitamin D deficiency may have been contributory. Because there is a high
      rate of inadequate vitamin D levels in patients undergoing orthopaedic surgery
      and a known impact on bone healing complications, post-operative bone fixation
      failure may also occur. This case report may therefore prompt further awareness
      for considering pre-surgical vitamin D deficiency screening in adults presenting
      with rare avulsion fractures, and may further demonstrate its impact on surgical
      outcomes. 

PMID- 24876464
TI  - The hunt for MH370.

PMID- 24876469
TI  - Science in China. Tiananmen's bitter legacy.

PMID- 24876470
TI  - Neuroscience. BRAIN project meets physics.

PMID- 24876471
TI  - Particle physics. Plan to internationalize U.S. project may face headwind.

PMID- 24876472
TI  - Scientific community. Psychologist's defense challenged.

PMID- 24876473
TI  - Interview. Where's France Cordova? In the Washington hot seat.

PMID- 24876474
TI  - Views of science clash in debate over NSF bill.

PMID- 24876475
TI  - Lost at sea.

PMID- 24876476
TI  - Six handshakes, then silence.

PMID- 24876477
TI  - Target small firms for antibiotic innovation.

PMID- 24876478
TI  - Imaging techniques. Mapping bond orientations with polarized x-rays.

PMID- 24876479
TI  - Translational genomics. Clues from the resilient.

PMID- 24876480
TI  - Biochemistry. A bacterial seek-and-destroy system for foreign DNA.

PMID- 24876481
TI  - Geochemistry. How sulfur beats iron.

PMID- 24876482
TI  - Ecology. Managing the side effects of invasion control.

PMID- 24876483
TI  - Physics. Hitting the limit of magnetic anisotropy.

PMID- 24876484
TI  - Retraction.

PMID- 24876485
TI  - CKDu in Sri Lanka.

PMID- 24876486
TI  - Fear beyond predators.

PMID- 24876487
TI  - Comment on "High-resolution global maps of 21st-century forest cover change".
AB  - Hansen et al. (Reports, 15 November 2013, p. 850) published a high-resolution
      global forest map with detailed information on local forest loss and gain. We
      show that their product does not distinguish tropical forests from plantations
      and even herbaceous crops, which leads to a substantial underestimate of forest
      loss and compromises its value for local policy decisions. 

PMID- 24876488
TI  - Response to comment on "High-resolution global maps of 21st-century forest cover
      change".
AB  - Tropek et al. critique the Hansen et al. global forest loss paper in terms of its
      utility and accuracy. Both criticisms suffer from a miscomprehension of the
      definition of forest employed as well as the requirements of product validation.
      Utility of the product is enhanced through its integration with forest type,
      carbon stock, protected area status, and other ancillary data. 

PMID- 24876489
TI  - Crystal structure of a heterotetrameric NMDA receptor ion channel.
AB  - N-Methyl-D-aspartate (NMDA) receptors belong to the family of ionotropic
      glutamate receptors, which mediate most excitatory synaptic transmission in
      mammalian brains. Calcium permeation triggered by activation of NMDA receptors is
      the pivotal event for initiation of neuronal plasticity. Here, we show the
      crystal structure of the intact heterotetrameric GluN1-GluN2B NMDA receptor ion
      channel at 4 angstroms. The NMDA receptors are arranged as a dimer of GluN1
      GluN2B heterodimers with the twofold symmetry axis running through the entire
      molecule composed of an amino terminal domain (ATD), a ligand-binding domain
      (LBD), and a transmembrane domain (TMD). The ATD and LBD are much more highly
      packed in the NMDA receptors than non-NMDA receptors, which may explain why ATD
      regulates ion channel activity in NMDA receptors but not in non-NMDA receptors.

PMID- 24876490
TI  - Labor market returns to an early childhood stimulation intervention in Jamaica.
AB  - A substantial literature shows that U.S. early childhood interventions have
      important long-term economic benefits. However, there is little evidence on this
      question for developing countries. We report substantial effects on the earnings
      of participants in a randomized intervention conducted in 1986-1987 that gave
      psychosocial stimulation to growth-stunted Jamaican toddlers. The intervention
      consisted of weekly visits from community health workers over a 2-year period
      that taught parenting skills and encouraged mothers and children to interact in
      ways that develop cognitive and socioemotional skills. The authors reinterviewed
      105 out of 129 study participants 20 years later and found that the intervention
      increased earnings by 25%, enough for them to catch up to the earnings of a
      nonstunted comparison group identified at baseline (65 out of 84 participants). 

PMID- 24876492
TI  - Amorphous TiO2 coatings stabilize Si, GaAs, and GaP photoanodes for efficient
      water oxidation.
AB  - Although semiconductors such as silicon (Si), gallium arsenide (GaAs), and
      gallium phosphide (GaP) have band gaps that make them efficient photoanodes for
      solar fuel production, these materials are unstable in aqueous media. We show
      that TiO2 coatings (4 to 143 nanometers thick) grown by atomic layer deposition
      prevent corrosion, have electronic defects that promote hole conduction, and are
      sufficiently transparent to reach the light-limited performance of protected
      semiconductors. In conjunction with a thin layer or islands of Ni oxide
      electrocatalysts, Si photoanodes exhibited continuous oxidation of 1.0 molar
      aqueous KOH to O2 for more than 100 hours at photocurrent densities of >30
      milliamperes per square centimeter and ~100% Faradaic efficiency. TiO2-coated
      GaAs and GaP photoelectrodes exhibited photovoltages of 0.81 and 0.59 V and light
      limiting photocurrent densities of 14.3 and 3.4 milliamperes per square
      centimeter, respectively, for water oxidation. 

PMID- 24876491
TI  - Coherent ultrafast charge transfer in an organic photovoltaic blend.
AB  - Blends of conjugated polymers and fullerene derivatives are prototype systems for
      organic photovoltaic devices. The primary charge-generation mechanism involves a
      light-induced ultrafast electron transfer from the light-absorbing and electron
      donating polymer to the fullerene electron acceptor. Here, we elucidate the
      initial quantum dynamics of this process. Experimentally, we observed coherent
      vibrational motion of the fullerene moiety after impulsive optical excitation of
      the polymer donor. Comparison with first-principle theoretical simulations
      evidences coherent electron transfer between donor and acceptor and oscillations
      of the transferred charge with a 25-femtosecond period matching that of the
      observed vibrational modes. Our results show that coherent vibronic coupling
      between electronic and nuclear degrees of freedom is of key importance in
      triggering charge delocalization and transfer in a noncovalently bound reference
      system. 

PMID- 24876493
TI  - Vibrational spectral signature of the proton defect in the three-dimensional
      H+(H2O)21 cluster.
AB  - The way in which a three-dimensional network of water molecules accommodates an
      excess proton is hard to discern from the broad vibrational spectra of dilute
      acids. The sharper bands displayed by cold gas-phase clusters, H(+)(H2O)n, are
      therefore useful because they encode the network-dependent speciation of the
      proton defect and yet are small enough to be accurately treated with electronic
      structure theory. We identified the previously elusive spectral signature of the
      proton defect in the three-dimensional cage structure adopted by the particularly
      stable H(+)(H2O)21 cluster. Cryogenically cooling the ion and tagging it with
      loosely bound deuterium (D2) enabled detection of its vibrational spectrum over
      the 600 to 4000 cm(-1) range. The excess charge is consistent with a
      tricoordinated H3O(+) moiety embedded on the surface of a clathrate-like cage. 

PMID- 24876494
TI  - X-ray birefringence imaging.
AB  - The polarizing optical microscope has been used since the 19th century to study
      the structural anisotropy of materials, based on the phenomenon of optical
      birefringence. In contrast, the phenomenon of x-ray birefringence has been
      demonstrated only recently and has been shown to be a sensitive probe of the
      orientational properties of individual molecules and/or bonds in anisotropic
      solids. Here, we report a technique-x-ray birefringence imaging (XBI)-that
      enables spatially resolved mapping of x-ray birefringence of materials,
      representing the x-ray analog of the polarizing optical microscope. Our results
      demonstrate the utility and potential of XBI as a sensitive technique for imaging
      the local orientational properties of anisotropic materials, including
      characterization of changes in molecular orientational ordering associated with
      solid-state phase transitions and identification of the size, spatial
      distribution, and temperature dependence of domain structures. 

PMID- 24876495
TI  - Quaternary coral reef refugia preserved fish diversity.
AB  - The most prominent pattern in global marine biogeography is the biodiversity peak
      in the Indo-Australian Archipelago. Yet the processes that underpin this pattern
      are still actively debated. By reconstructing global marine paleoenvironments
      over the past 3 million years on the basis of sediment cores, we assessed the
      extent to which Quaternary climate fluctuations can explain global variation in
      current reef fish richness. Comparing global historical coral reef habitat
      availability with the present-day distribution of 6316 reef fish species, we find
      that distance from stable coral reef habitats during historical periods of
      habitat loss explains 62% of the variation in fish richness, outweighing present
      day environmental factors. Our results highlight the importance of habitat
      persistence during periods of climate change for preserving marine biodiversity. 

PMID- 24876496
TI  - Composition of isolated synaptic boutons reveals the amounts of vesicle
      trafficking proteins.
AB  - Synaptic vesicle recycling has long served as a model for the general mechanisms
      of cellular trafficking. We used an integrative approach, combining quantitative
      immunoblotting and mass spectrometry to determine protein numbers; electron
      microscopy to measure organelle numbers, sizes, and positions; and super
      resolution fluorescence microscopy to localize the proteins. Using these data, we
      generated a three-dimensional model of an "average" synapse, displaying 300,000
      proteins in atomic detail. The copy numbers of proteins involved in the same step
      of synaptic vesicle recycling correlated closely. In contrast, copy numbers
      varied over more than three orders of magnitude between steps, from about 150
      copies for the endosomal fusion proteins to more than 20,000 for the exocytotic
      ones. 

PMID- 24876497
TI  - Optimal approaches for balancing invasive species eradication and endangered
      species management.
AB  - Resolving conflicting ecosystem management goals-such as maintaining fisheries
      while conserving marine species or harvesting timber while preserving habitat-is
      a widely recognized challenge. Even more challenging may be conflicts between two
      conservation goals that are typically considered complementary. Here, we model a
      case where eradication of an invasive plant, hybrid Spartina, threatens the
      recovery of an endangered bird that uses Spartina for nesting. Achieving both
      goals requires restoration of native Spartina. We show that the optimal
      management entails less intensive treatment over longer time scales to fit with
      the time scale of natural processes. In contrast, both eradication and
      restoration, when considered separately, would optimally proceed as fast as
      possible. Thus, managers should simultaneously consider multiple, potentially
      conflicting goals, which may require flexibility in the timing of expenditures. 

PMID- 24876498
TI  - High-resolution mapping of intracellular fluctuations using carbon nanotubes.
AB  - Cells are active systems with molecular force generation that drives complex
      dynamics at the supramolecular scale. We present a quantitative study of
      molecular motions in cells over times from milliseconds to hours. Noninvasive
      tracking was accomplished by imaging highly stable near-infrared luminescence of
      single-walled carbon nanotubes targeted to kinesin-1 motor proteins in COS-7
      cells. We observed a regime of active random "stirring" that constitutes an
      intermediate mode of transport, different from both thermal diffusion and
      directed motor activity. High-frequency motion was found to be thermally driven.
      At times greater than 100 milliseconds, nonequilibrium dynamics dominated. In
      addition to directed transport along microtubules, we observed strong random
      dynamics driven by myosins that result in enhanced nonspecific transport. We
      present a quantitative model connecting molecular mechanisms to mesoscopic
      fluctuations. 

PMID- 24876500
TI  - Winter is coming.

PMID- 24876501
TI  - The biodiversity of species and their rates of extinction, distribution, and
      protection.
AB  - Recent studies clarify where the most vulnerable species live, where and how
      humanity changes the planet, and how this drives extinctions. We assess key
      statistics about species, their distribution, and their status. Most are
      undescribed. Those we know best have large geographical ranges and are often
      common within them. Most known species have small ranges. The numbers of small
      ranged species are increasing quickly, even in well-known taxa. They are
      geographically concentrated and are disproportionately likely to be threatened or
      already extinct. Current rates of extinction are about 1000 times the likely
      background rate of extinction. Future rates depend on many factors and are poised
      to increase. Although there has been rapid progress in developing protected
      areas, such efforts are not ecologically representative, nor do they optimally
      protect biodiversity. 

PMID- 24876502
TI  - Adrenocortical carcinoma posing as a pheochromocytoma: a diagnostic dilemma.
AB  - Adrenocortical carcinoma (ACC) is a malignant tumour arising from the adrenal
      cortex, whereas pheochromocytoma is a tumour of the adrenal medulla with
      occasional presence at extra-adrenal sites. Most of the adrenocortical tumours
      present clinically with Cushing's syndrome and signs of virilization due to over
      production of the respective hormones. It is, however, rare for an adrenocortical
      tumour to present clinically as a pheochromocytoma. We report the case of a 45
      year-old female presenting with clinical symptoms and signs of pheochromocytoma
      and investigations that resulted in a diagnostic dilemma. The histopathological
      examination confirmed the presence of ACC after the tumour was excised. This
      phenomenon was due to the presence of neuroendocrine features of ACC referred to,
      as a pseudo-pheochromocytoma with extremely limited data in the literature. 

PMID- 24876499
TI  - Structures of PI4KIIIbeta complexes show simultaneous recruitment of Rab11 and
      its effectors.
AB  - Phosphatidylinositol 4-kinases (PI4Ks) and small guanosine triphosphatases
      (GTPases) are essential for processes that require expansion and remodeling of
      phosphatidylinositol 4-phosphate (PI4P)-containing membranes, including
      cytokinesis, intracellular development of malarial pathogens, and replication of
      a wide range of RNA viruses. However, the structural basis for coordination of
      PI4K, GTPases, and their effectors is unknown. Here, we describe structures of
      PI4Kbeta (PI4KIIIbeta) bound to the small GTPase Rab11a without and with the
      Rab11 effector protein FIP3. The Rab11-PI4KIIIbeta interface is distinct compared
      with known structures of Rab complexes and does not involve switch regions used
      by GTPase effectors. Our data provide a mechanism for how PI4KIIIbeta coordinates
      Rab11 and its effectors on PI4P-enriched membranes and also provide strategies
      for the design of specific inhibitors that could potentially target plasmodial
      PI4KIIIbeta to combat malaria. 

PMID- 24876503
TI  - Recurrent wound dehiscence and small bowel herniation following Caesarean section
      in a woman with hidradenitis suppurativa.
AB  - Caesarean wound dehiscence that is severe enough to result in bowel herniation is
      exceptionally rare. This case describes a woman who experienced wound dehiscence
      following each of her two Caesarean sections, with bowel herniation present in
      the second case. The contribution of her comorbid hidradenitis suppurativa will
      be discussed. 

PMID- 24876504
TI  - Mediastinal emphysema following fracture of the orbital floor.
AB  - Pneumomediastinum (PM) is mainly an atypical finding among traumatic neck or
      thoracic injury patients. Moreover, PM secondary to isolated orbital floor
      fracture remains a rare event which is infrequently associated with severe
      complications such as mediastinitis, airway obstruction and pneumothorax. Herein,
      we report an atypical case of mediastinal emphysema consequent to orbital floor
      fracture along with review of the literature. 

PMID- 24876505
TI  - Gastropleural fistula in metastatic ovarian cancer.
AB  - Gastropleural fistula is a rare condition, most frequently reported as a result
      of trauma, peptic ulcer disease or malignancy. We report a case of gastropleural
      fistula in a patient with metastatic ovarian cancer who presented with
      hydropneumothorax and mediastinal shift. She was successfully managed with an
      open partial gastrectomy, repair of diaphragmatic defect, and thoracoscopic
      washout and decortication. Based on our case and review of the literature,
      surgical repair of gastropleural fistula should be considered as a palliative
      procedure even in patients with end-stage cancer. 

PMID- 24876506
TI  - Secondary repair of severe chronic fourth-degree perineal tear due to obstetric
      trauma.
AB  - Obstetric injury is the commonest cause of anal incontinence. We report a case of
      anal incontinence as a result of severe chronic fourth-degree perineal tear
      secondary to birthing with complete disruption of the perineum. Secondary repair
      consisting of an anterior sphincter repair and levatorplasty in a poor resourced
      area rendered excellent immediate clinical result. The outcome of anterior
      sphincter repair following obstetric trauma is good but long-term follow-up is
      required because of the underlying complexity of obstetric injury. As prevention
      is not always possible, immediate recognition and adequate primary treatment is
      of importance. 

PMID- 24876507
TI  - Small bowel obstruction caused by sigmoid mesocolic hernia.
AB  - Internal hernia is an unusual cause of small bowel obstruction and classified
      several types according to locations. Sigmoid mesocolic hernia is an uncommon
      condition and among others intramesosigmoid hernia was rarely reported in the
      literature. We report the case of a 49-year-old female with a rare type of
      congenital internal hernia, through the mesosigmoid, causing small bowel
      obstruction. She suffered from obstructive symptoms but with no previous history
      of laparotomy. The diagnosis of internal hernia was suggested by computed
      tomography, but the type of internal hernia was confirmed by laparoscopic
      exploration. She underwent laparoscopic detachment of peritoneal attachment
      comprising hernia sac without defect repair. The postoperative course was
      uneventful and the patient is free from symptoms and recurrence. This report
      presents a case of intrasigmoid hernia managed successfully by the laparoscopic
      approach and shows another surgical technique according to hernia types. 

PMID- 24876508
TI  - Enterocolic lymphocytic phlebitis: an oncologic surgical resection without a
      preoperative pathologic diagnosis.
AB  - A patient with complaints of an abdominal (mesenteric) mass is presented.
      Differential diagnosis included neoplastic processes, such as malignant lymphoma,
      desmoid tumour, a carcinoid or a gastro-intestinal stromal cell tumour. An
      oncological resection was performed. Despite the malignant appearance of the
      tumour no malignancy was found with histopathological examination. Vasculitic
      lesions were seen in venous structures, resembling veno-occlusive disease with
      signs of recanalization and with the presence of inflammatory cells, mainly
      lymphocytes. A diagnosis of enterocolic lymphocytic phlebitis was made. This
      benign condition can mimic malignancy, necessitating a wide excision, also
      because obtaining a pre-operative histopathological diagnosis is hardly possible.

PMID- 24876509
TI  - Flexor digitorum profundus entrapment in paediatric forearm fractures.
AB  - Entrapment of the flexor digitorum profundus (FDP) is a recognized complication
      of paediatric both-bone forearm fractures. Although a rare complication, it is
      usually missed at the time of initial fracture management resulting in the need
      for corrective surgery. An attempted closed manipulation followed by immediate
      surgical correction of FDP entrapment in our hospital prompted a review of the
      evidence on this underreported problem. A comprehensive English language
      literature search was performed using Embase, Medline and Pubmed. Twenty cases
      have been reported in the literature and all were diagnosed post-operatively
      (range 2 days-16 years). Eighteen cases (90%) required surgical correction. Five
      cases (25%) were initially diagnosed as mild Volkmann's contracture yet at
      surgery no case was found to have evidence of previous muscle ischaemia. Although
      subclinical or mild Volkmann's ischaemic contracture is a recognized complication
      of closed forearm fracture, this report highlights the importance of considering
      a diagnosis of muscle entrapment in cases of flexion contracture. 

PMID- 24876510
TI  - Exacerbation of left ventricular outlet obstruction in hypertrophic obstructive
      cardiomyopathy: an unexpected complication of gastric banding.
AB  - Hypertrophic obstructive cardiomyopathy (HOCM) is characterized by a dynamic left
      ventricular outlet tract (LVOT) obstruction, which may be exacerbated by reduced
      preload and Valsalva. Laparoscopic adjustable gastric band (LAGB) placement is a
      restrictive bariatric procedure which may be complicated by recurrent vomiting
      and Valsalva. Pre-operative cardiac evaluation of patients scheduled for LAGB
      usually focuses on ischemic heart disease. Reported here is the case of a 64-year
      old female admitted for evaluation of recurrent pre-syncopal episodes. The
      patient was diagnosed with HOCM with a significant increase in an LVOT pressure
      gradient during Valsalva. Thus, recurrent vomiting secondary to LAGB exacerbated
      a pre-existing cardiomyopathy. Symptoms resolved after gastric band deflation.
      This is the first report of such a complication after LAGB, demonstrating the
      hemodynamics of HOCM in a unique setting and underscoring the need for a
      structural cardiac assessment prior to bariatric surgery. 

PMID- 24876511
TI  - Open perilunate injury with lunate revascularization after complete ligamentous
      avulsion.
AB  - Perilunate dislocations are a devastating injury to the carpus that carry a
      guarded long-term prognosis. Mayfield type 4 perilunate dislocations are rare,
      high-energy injuries that carry a risk for avascular necrosis (AVN) of the
      lunate. When AVN ensues and the carpus collapses, primary treatment with a
      proximal row carpectomy or arthrodesis has been advocated. This case reports a
      successful clinical result and revascularization of an extruded lunate with open
      reduction and internal fixation. This type 4, Gustilo grade 1 open perilunate
      dislocation exhibited complete avulsion of all lunate ligamentous attachments.
      Management included open reduction and internal fixation as well as carpal tunnel
      release through a combined dorsal and volar approach. Despite concerns for lunate
      AVN due to complete disruption of lunate vascularity, a 10-month postoperative
      clinical and radiographic examination demonstrated no pain with activities of
      daily living as well as a revascularized lunate. 

PMID- 24876512
TI  - Colo-articular fistula following a Girdlestone resection arthroplasty.
AB  - Colo-articular fistulas are rare complications that are usually associated with
      inflammatory, infective or malignant bowel disease. We report the case of a 44
      year-old male who was found to have a colo-articular fistula intra-operatively
      during the washout of a septic hip joint. The patient had no pre-existing bowel
      disease, but was an intravenous drug user, who had previously undergone a
      Girdlestone procedure for osteomyelitis of the proximal femur. The patient was
      managed through a multi-disciplinary team approach with subsequent debridement
      and formation of a transverse loop colostomy to control the faeculent fistulous
      discharge. 

PMID- 24876513
TI  - Trocar site hernias from using bladeless trocars: should fascial closure be
      performed?
AB  - Laparoscopic surgery is the modality of choice in the surgical treatment of
      colorectal malignancies. The reported incidence of trocar site hernias is 0.65
      2.80% with conventional cutting-tip trocars, and this risk increases with the
      diameter of the trocar. Newer bladeless, blunt-tipped trocars effectively
      mitigate this risk, and routine fascial closure has been generally deemed
      unnecessary. We present two cases of trocar site hernias despite the use of
      bladeless trocars in laparoscopic colorectal surgery, challenging the
      conventional wisdom of leaving such fascial defects open. 

PMID- 24876514
TI  - A rare presentation of triple-negative apocrine breast carcinoma with metastases.
AB  - Apocrine breast carcinoma is a rare subtype of the invasive ductal carcinoma and
      accounts for as little as 0.3-1% of all breast cancers. It is usually positive
      for human epidermal growth factor receptor 2 (HER-2) and negative for both
      estrogen receptor and progesterone receptor. Here we present an exceptionally
      rare case of apocrine breast carcinoma that is a triple receptor negative with
      metastases and to our knowledge this is the first published case. This is a
      significant finding because it implies that the tumor would not respond to the
      typical hormonal agents. This case highlights the need for studies to elucidate
      better treatment strategies for these types of patients. 

PMID- 24876515
TI  - Endometriosis within a left-sided inguinal hernia sac.
AB  - Endometriosis is a common gynecologic disorder wherein ectopic endometrial glands
      and stroma are found at extrauterine sites. Extrapelvic endometriosis is a well
      documented, yet rare, disease entity that can affect almost any organ system.
      Inguinal endometriosis is an extremely rare disease entity characterized by
      tender inguinal swelling. Here we report a case of a sudden-onset and acutely
      painful left inguinal hernia with concordant endometriosis. A review of the
      literature is presented. The presence of isolated endometriosis contained within
      a left-sided inguinal hernia sac has, to our knowledge, never been reported.
      Often diagnosed incidentally or on histologic examination, general surgeons
      should consider inguinal endometriosis in the differential diagnosis of inguinal
      masses, even in the absence of catamenial symptoms. Surgical excision, with
      gynecologic follow-up, is locally curative and the treatment of choice for
      inguinal endometriosis. 

PMID- 24876516
TI  - Immediate postoperative parastomal end sigmoid hernia resulting in evisceration
      and strangulation.
AB  - Parastomal evisceration is a very rare complication occurring after stoma
      formation. We report the case of this complication which occurred within 3 days
      status post end sigmoid colostomy in a 69-year-old male who initially presented
      with perianal infection-severe necrotizing fasciitis. This case highlights the
      significance of the size of a stomatal aperture and should remind general
      surgeons of the one of dangerous complications indicated by a stomatal aperture
      that is just a centimeter larger than the accepted ideal size. 

PMID- 24876517
TI  - Suspected incisional hernia leading to resection of rib sequestrum: a rare case
      report.
AB  - Intercostal incisional hernias are rarely encountered post-operative
      complications. Bone sequestra of the ribs are similarly rare. We report a very
      rare case of a left sided rib bone sequestrum mimicking an incisional hernia
      after a nephrectomy, splenectomy, and distal pancreatectomy. 

PMID- 24876518
TI  - Primary mesenteric gastrointestinal stromal tumour.
AB  - Primary mesenteric gastrointestinal stromal tumours (GISTs) are rare tumours and
      can be included as a differential for an expanding intraabdominal mass. We
      present the case, in our institution, of a 72-year-old male who presented with
      non-specific symptoms and was diagnosed with a primary mesenteric GIST following
      resection. We report his follow-up and discuss the current theories as to the
      origins of these rare tumours and current treatment modalities. 

PMID- 24876519
TI  - Isolated partial, transient hypoglossal nerve injury following acupuncture.
AB  - We report a case of isolated unilateral hypoglossal nerve injury following
      ipsilateral acupuncture for migraines in a 53-year-old lady. The palsy was
      partial, with no associated dysarthria, and transient. Further examination and
      imaging was negative. Cranial nerve injuries secondary to acupuncture are not
      reported in the literature, but are a theoretical risk given the location of the
      cranial nerves in the neck. Anatomical knowledge is essential in those
      administering the treatment, and those reviewing patients with possible
      complications. 

PMID- 24876520
TI  - Hybrid repair of aortic arch pathology.
AB  - The objective was to evaluate a 13-year single-centre experience of arch
      endovascular aortic repair using the hybrid approach. Between 1999 and 2013, 491
      patients were treated with endografts for thoracic aortic pathologies. The aortic
      arch was involved in 179 (36.5%) patients (128 men; mean age 70.2 +/- 10.8 years,
      range 27-84). A hybrid approach was performed for all Zone 0 and 1 procedures and
      in nearly half of Zone 2 procedures. Early and mid-term outcomes were reviewed
      retrospectively. Overall primary technical success (24 h) was achieved in 162
      (90.5%) of the 179 cases; 2 deaths and 15 Type 1 endoleaks were observed.
      Clinical success at 30 days was achieved in 161 (89.9%) of the 179 patients, with
      a mortality rate of 4.5% (8/179). Short-term clinical success at 6 months was
      achieved in 169 (94.4%) of the 179 patients; the rates for the different landing
      zones did not differ significantly. At a mean follow-up of 27.3 +/- 15.7 months
      (range 1-94), the mid-term clinical success was 165 (92.2%) of the 179 patients;
      the rates among the different proximal zones did not differ significantly. In
      selected patients, early and mid-term outcomes of arch endovascular aortic repair
      using the hybrid approach are promising; however, mortality and morbidity are not
      negligible. Our results may have practical implications for the ongoing
      evaluation of the hybrid procedure in the aortic arch, as well as for patients
      fit for traditional surgery.

PMID- 24876521
TI  - Of mice and men....

PMID- 24876522
TI  - CLL and NHL: the end of chemotherapy?

PMID- 24876523
TI  - p57(Kip2) regulates T-cell development and lymphoma.

PMID- 24876524
TI  - The missing link in early follicular lymphoma development.

PMID- 24876525
TI  - A(nother) day in the life of neonatal platelets.

PMID- 24876526
TI  - Antibodies in APS with competing interest.

PMID- 24876527
TI  - Bye-bye TRALI: by understanding and innovation.

PMID- 24876528
TI  - Siglec-G signaling DAMPens GVHD.

PMID- 24876529
TI  - New Wearable Computers Move Ahead: Google Glass and Smart Wigs.

PMID- 24876530
TI  - Biosimilar Insulins: Basic Considerations.
AB  - Until now most of the insulin used in developed countries has been manufactured
      and distributed by a small number of multinational companies. Beyond the
      established insulin manufacturers, a number of new players have developed insulin
      manufacturing capacities based on modern biotechnological methods. Because the
      patents for many of the approved insulin formulations have expired or are going
      to expire soon, these not yet established companies are increasingly interested
      in seeking market approval for their insulin products as biosimilar insulins (BI)
      in highly regulated markets like the EU and the United States. Differences in the
      manufacturing process (none of the insulin manufacturing procedures are 100%
      identical) can lead to insulins that to some extent may differ from the
      originator insulin. The key questions are if subtle differences in the structure
      of the insulins, purity, and so on are clinically relevant and may result in
      different biological effects. The aim of this article is to introduce and discuss
      basic aspects that may be of relevance with regard to BI.

PMID- 24876531
TI  - Drug Development and Potential Regulatory Paths for Insulin Biosimilars.
AB  - Under the Biologics Price Competition and Innovation Act (BPCI Act), a biological
      product may be demonstrated to be "biosimilar" if data show that, among other
      things, the product is "highly similar" to an already-approved biological
      product. Biosimilar insulins have the potential to reduce ever growing costs
      associated with insulin treatment by allowing competition. In this article, we
      describe the current drug development and regulatory paths for biosimilar
      insulins. Most likely basis of market approval for biosimilar insulins by the US
      Food and Drug Administration (FDA) and guidance for developing insulin
      biosimilars by European Medicines Agency (EMA) are discussed in detail.
      Currently, no product specific biosimilar FDA guidance for insulin biosimilarity
      assessment exists. We propose efficient and cost-effective drug development and
      potential regulatory paths based on scientific justification. In addition, novel
      trial designs for demonstrating interchangeability between the biosimilar and the
      reference insulin products are presented.

PMID- 24876532
TI  - Multiple Source Biosimilar Insulin, What's a Provider to Do?
AB  - In the United States the FDA designates generic products that are bioequivalent
      as AB substitutable (FDA rating signifying the approved application contains
      adequate scientific evidence establishing through in vivo and/or in vitro studies
      the bioequivalence of the product to a selected reference product) and are
      expected to produce the same therapeutic results as the innovator product. In the
      case of biological proteins that are similar to already approved innovator
      biologicals, such as recombinant human insulin, the insulin molecule and
      accompanying secondary and tertiary structures will differ between manufacturing
      sources. Even subtle differences between innovator (branded) and alternative
      "biosimilar" products may produce different therapeutic endpoints. Substitution
      of a branded insulin with a biosimilar insulin product may result in more, less,
      or equal therapeutic response making in difficult for the practitioner to assess
      glycemic control between patient follow-up visits. Significant therapeutic
      difference is possible, which could result in mild to severe hypoglycemia
      reaction or hyperglycemia induced tissue damage. Slight molecular changes along
      with different accompanying proteins, protein fragments, and other naturally
      occurring contaminants theoretically increase odds of insulin resistance or
      allergic reaction. Current review of medication product and device quality relies
      on manufacturer self-oversight and individual reporting of product adverse events
      after use. While this is usually sufficient for oral medications and many medical
      devices, critical use products such as sterile products, biosimilar insulin,
      insulin delivery devices, self-monitoring blood glucose monitoring systems, and
      test strips require much more vigorous oversight to prevent individual and/or
      large scale catastrophe. Health care providers should advocate for their patient
      to have access to affordable, consistent, quality-assured products to effectively
      and safely manage their medical issues. A potential commonsense solution would be
      to utilize existing nonprofit organizations with access to pharmacy/laboratory
      services that have vested interest in ensuring product quality throughout the
      supply pipeline. The old adage "an ounce of prevention is worth a pound of cure"
      holds even more true in today's medical environment.

PMID- 24876533
TI  - Patient Perspectives on Biosimilar Insulin.
AB  - Given that a new wave of biosimilar insulins will likely enter the market in
      coming years, it is important to understand patient perspectives on these
      biosimilars. A survey (N = 3214) conducted by the market research company dQ&A,
      which maintains a 10 000-patient panel of people with type 1 or type 2 diabetes
      in roughly equal measure, investigated these perspectives. The survey asked
      whether patients would switch to a hypothetical less expensive biosimilar insulin
      that was approved by their provider. Approximately 66% of respondents reported
      that they would "definitely" or "likely" use a biosimilar insulin, while 17%
      reported that they were "unlikely" to use or would "definitely not use" such a
      product. Type 2 diabetes patients demonstrated slightly more willingness to use
      biosimilars than type 1 diabetes patients. Common patient concerns included
      whether biosimilars would be as effective as reference products (~650
      respondents), whether side effect profiles would deviate from those of reference
      products (~220 respondents), and the design of the delivery device (~50
      respondents). While cost savings associated with biosimilar insulins could
      increase patient uptake, especially among patients without health insurance (some
      recent estimates suggest that biosimilars will come at a substantial discount),
      patients may still need assurance that a cheaper price tag is not necessarily
      associated with substandard quality. Overall, the dQ&A survey indicates that the
      majority of patients are willing to consider biosimilar insulins, but
      manufacturers will need to work proactively to address and assuage patient
      concerns regarding efficacy, safety, drug administration, and other factors.

PMID- 24876534
TI  - The UVA/PADOVA Type 1 Diabetes Simulator: New Features.
AB  - Recent studies have provided new insights into nonlinearities of insulin action
      in the hypoglycemic range and into glucagon kinetics as it relates to response to
      hypoglycemia. Based on these data, we developed a new version of the UVA/PADOVA
      Type 1 Diabetes Simulator, which was submitted to FDA in 2013 (S2013). The model
      of glucose kinetics in hypoglycemia has been improved, implementing the notion
      that insulin-dependent utilization increases nonlinearly when glucose decreases
      below a certain threshold. In addition, glucagon kinetics and secretion and
      action models have been incorporated into the simulator: glucagon kinetics is a
      single compartment; glucagon secretion is controlled by plasma insulin, plasma
      glucose below a certain threshold, and glucose rate of change; and plasma
      glucagon stimulates with some delay endogenous glucose production. A refined
      statistical strategy for virtual patient generation has been adopted as well.
      Finally, new rules for determining insulin to carbs ratio (CR) and correction
      factor (CF) of the virtual patients have been implemented to better comply with
      clinical definitions. S2013 shows a better performance in describing hypoglycemic
      events. In addition, the new virtual subjects span well the real type 1 diabetes
      mellitus population as demonstrated by good agreement between real and simulated
      distribution of patient-specific parameters, such as CR and CF. S2013 provides a
      more reliable framework for in silico trials, for testing glucose sensors and
      insulin augmented pump prediction methods, and for closed-loop single/dual
      hormone controller design, testing, and validation.

PMID- 24876535
TI  - Closed-Loop Control Performance of the Hypoglycemia-Hyperglycemia Minimizer (HHM)
      System in a Feasibility Study.
AB  - BACKGROUND: This feasibility study investigated the insulin-delivery
      characteristics of the Hypoglycemia-Hyperglycemia Minimizer (HHM) System-an
      automated insulin delivery device-in participants with type 1 diabetes. METHODS:
      Thirteen adults with type 1 diabetes were enrolled in this nonrandomized,
      uncontrolled, clinical-research-center-based feasibility study. The HHM System
      comprised a continuous subcutaneous insulin infusion pump, a continuous glucose
      monitor (CGM), and a model predictive control algorithm with a safety module, run
      on a laptop platform. Closed-loop control lasted approximately 20 hours,
      including an overnight period and two meals. RESULTS: When attempting to minimize
      glucose excursions outside of a prespecified target zone, the predictive HHM
      System decreased insulin infusion rates below the participants' preset basal
      rates in advance of below-zone excursions (CGM < 90 mg/dl), and delivered 80.4%
      less insulin than basal during those excursions. Similarly, the HHM System
      increased infusion rates above basal during above-zone excursions (CGM > 140
      mg/dl), delivering 39.9% more insulin than basal during those excursions. Based
      on YSI, participants spent a mean +/- standard deviation (SD) of 0.2 +/- 0.5% of
      the closed-loop control time at glucose levels < 70 mg/dl, including 0.3 +/- 0.9%
      for the overnight period. The mean +/- SD glucose based on YSI for all
      participants was 164.5 +/- 23.5 mg/dl. There were nine instances of algorithm
      recommended supplemental carbohydrate administrations, and there was no severe
      hypoglycemia or diabetic ketoacidosis. CONCLUSIONS: Results of this study
      indicate that the current HHM System is a feasible foundation for development of
      a closed-loop insulin delivery device.

PMID- 24876536
TI  - Measurement of Lens Autofluorescence Can Distinguish Subjects With Diabetes From
      Those Without.
AB  - Lens autofluorescence is increased in patients with diabetes mellitus, but
      clinical application has been limited by the lack of an instrument suitable for
      routine clinical use. We investigate possible uses of a new scanning confocal
      biomicroscope (1) to identify subjects with undiagnosed type 2 diabetes and (2)
      as a marker for the progression of diabetes. One hundred seventy-eight subjects
      self-reported as normal and 53 subjects physician-diagnosed with diabetes or
      prediabetes were recruited. Measurements were collected using a ClearPath DS-120
      Lens Fluorescence Biomicroscope calibrated with standards traceable to National
      Institute of Standards and Technology (NIST). Fluorescence intensities were
      corrected for age by subtracting the value expected from a regression of
      intensity versus age for normal subjects. This "fluorescence deviation" showed
      progressively higher values for normal, prediabetes, type 2 diabetes, and type 1
      diabetes and a high degree of predictability of diabetes diagnosis. A receiver
      operating characteristics curve was used to determine sensitivity and specificity
      for prediction of diabetes type 2. At a fluorescence deviation of 2500, a
      sensitivity of 67% at 94% specificity was observed detection of type 2 diabetes.
      The progressively higher fluorescence deviations are consistent with the
      physiological mechanisms of accumulation of fluorescent advanced glycation end
      products as the subject ages. The sensitivity and specificity performance of the
      lens autofluorescence test for type 2 diabetes is comparable to the performance
      of glucose threshold tests. The statistically significant difference between
      fluorescence deviations of normal and type 2 diabetes supports the feasibility of
      lens autofluorescence to screen subjects for undiagnosed type 2 diabetes.
      Ophthalmic practices are points of care at which there may be a public health
      benefit for screening patients for undiagnosed diabetes.

PMID- 24876537
TI  - Measurement of Lens Autofluorescence for Diabetes Screening.
AB  - Many efforts have been made lately to develop cost-effective, simple, and
      reproducible tests for diabetes screening besides the already established fasting
      plasma glucose, the oral glucose tolerance test, and the glycated hemoglobin A1c.
      Several tests have been proposed lately, based on the measurement of the so
      called advanced glycation endproducts (AGEs). AGEs production is exacerbated
      during hyperglycemia, and their accumulation in different tissues reflects the
      degree and duration of dysglycemia. The human lens represents a tissue where AGEs
      accumulation can be particularly well assessed. The present article comments on
      the article by Cahn et al. published in this issue of the Journal of Diabetes
      Science and Technology. Cahn and coauthors tested a new scanning confocal
      biomicroscope for its accuracy to detect noninvasively subjects with diabetes or
      at risk for developing diabetes.

PMID- 24876538
TI  - Accuracy of a Novel Noninvasive Multisensor Technology to Estimate Glucose in
      Diabetic Subjects During Dynamic Conditions.
AB  - The purpose of this study was to determine whether an approach of multisensor
      technology with integrated data analysis in an armband system (SenseWear(r) Pro
      Armband, SWA) can provide estimates of plasma glucose concentration in diabetes.
      In all, 41 subjects with diabetes participated. On day 1 subjects underwent an
      oral glucose tolerance test (OGTT) and on day 2 a 60-minute treadmill test (TT).
      SWA plasma glucose estimates were compared against reference peripheral venous
      glucose concentrations. A continuous glucose monitoring device (CGM) was also
      placed on each subject to serve as a reference for clinical comparison. Pearson
      coefficient, Clarke error grid (CEG), and mean absolute relative difference
      (MARD) analyses were used to compare the performance of plasma glucose
      estimation. There were significant correlations between plasma glucose
      concentrations estimated by the SWA and the reference plasma glucose
      concentration during the OGTT (r = .65, P < .05) and the TT (r = .91, P < .05).
      CEG analysis revealed that during the OGTT, 93% of plasma glucose concentration
      readings were in the clinically acceptable zone A+B for the SWA and 95% for the
      CGM. During the TT, the SWA had 96% of readings in zone A+B, compared to 97% for
      the CGM. During OGTTs, MARDs for the SWA and CGM were 26% and 18%, respectively.
      During TTs, MARDs were 16% and 12%, respectively. Plasma glucose concentration
      estimation by the SWA's noninvasive multisensor approach appears to be feasible
      and its performance in estimating glucose approaches that of a CGM. The success
      of this pilot study suggests that multisensor technology holds promising
      potential for the development of a wearable, noninvasive, painless glucose
      monitor.

PMID- 24876539
TI  - The Impact of Accelerometer and Heart Rate Data on Hypoglycemia Mitigation in
      Type 1 Diabetes.
AB  - Aerobic exercise can lower blood glucose levels and alter insulin sensitivity
      both during and several hours after exercise, creating challenges for a closed
      loop artificial pancreas. Predictive low glucose suspend (PLGS) algorithms are a
      first step toward an artificial pancreas, but few of these have been successfully
      applied to exercise. This study incorporates physical activity measurements from
      a combined accelerometer/heart rate monitor (HRM) to improve the performance of
      an existing PLGS algorithm at mitigating exercise-associated hypoglycemia in
      participants with type 1 diabetes. In all, 22 subjects with type 1 diabetes on
      insulin pump therapy were provided a combined accelerometer/HRM and (if not
      already using one) a continuous glucose monitor (CGM), then instructed to go
      about their everyday lives while wearing the devices. After the monitoring
      period, each subject's insulin pump, CGM, and accelerometer/HRM were downloaded
      and the data were used to augment an existing PLGS algorithm to incorporate
      activity. Using a computer simulator, the accelerometer-augmented algorithm was
      compared to the HRM-augmented algorithm to determine which was most effective at
      mitigating hypoglycemia. Mean length of monitoring was 4.9 days. Across all
      subjects, 11 061 CGM readings were recorded during the monitoring period. In the
      simulator analysis, the PLGS algorithm reduced hypoglycemia by 62%, compared to
      71% and 74% reductions for the HRM-augmented and accelerometer-augmented
      algorithms, respectively; combined accelerometer and HRM augmentation provided a
      76% reduction. In a simulated setting, the accelerometer-augmented pump
      suspension algorithm decreases the incidence of exercise-related hypoglycemia by
      a meaningful amount compared to the PLGS algorithm alone. Results also failed to
      justify the additional user burden of a HRM.

PMID- 24876540
TI  - Average Daily Risk Range (ADRR) in Young Children With Type 1 Diabetes.
AB  - OBJECTIVE: The objective was to examine the utility of the average daily risk
      range (ADRR) in young children with type 1 diabetes. METHODS: Self-monitored
      blood glucose (BG) data and A1c values were collected from 134 children (ages 2
      6). Other measures of BG variability and diabetes care were calculated using self
      monitored BG data. ADRR, A1c, and other glycemic indices were compared to assess
      their distinctiveness and utility as measures of BG variability and glycemic
      control. RESULTS: Of young children's ADRR values, 72% were in the "high-risk"
      range using adult guidelines. ADRR and A1c were highly correlated with indicators
      of hyperglycemia but only weakly correlated with measures of hypoglycemia. ADRR
      was moderately correlated with minimum BG value in the past 30 days but not
      percentage of BG values below 70 mg/dL. A1c was not correlated with either
      measure of hypoglycemia. CONCLUSIONS: ADRR values confirm the high degree of BG
      variability present in young children with type 1 diabetes, particularly as
      compared with adults. New ADRR risk guidelines are needed for pediatric patients.
      ADRR and A1c are adequate indicators of hyperglycemia in young children. However,
      both ADRR and A1c failed to effectively capture hypoglycemia risk in this sample,
      and neither ADRR nor A1c can take the place of review of raw BG data to evaluate
      BG variability in young children.

PMID- 24876541
TI  - Using Patient-Generated Health Data From Mobile Technologies for Diabetes Self
      Management Support: Provider Perspectives From an Academic Medical Center.
AB  - BACKGROUND: Mobile health and patient-generated health data are promising health
      IT tools for delivering self-management support in diabetes, but little is known
      about provider perspectives on how best to integrate these programs into routine
      care. We explored provider perceptions of a patient-generated health data report
      from a text-message-based diabetes self-management program. The report was
      designed to relay clinically relevant data obtained from participants' responses
      to self-assessment questions delivered over text message. METHODS: Likert-type
      scale response surveys and in-depth interviews were conducted with primary care
      physicians and endocrinologists who pilot tested the patient-generated health
      data report in an actual clinical encounter. Interview guides were designed to
      assess providers' perceptions of the feasibility and utility of patient-generated
      health data in routine clinical practice. Interviews were audiotaped,
      transcribed, and analyzed using the constant comparative method. RESULTS: Twelve
      providers successfully piloted the summary report in clinic. Although only a
      minority of providers felt the report changed the care they provided (3 of 12 or
      25%), most were willing to use the summary report in a future clinical encounter
      (9 of 12 or 75%). Perceived benefits of patient-generated health data included
      agenda setting, assessment of self-care, and identification of patient barriers.
      Major themes discussed included patient selection, reliability of patient
      generated health information, and integration into clinical workflow. CONCLUSION:
      Providers perceived multiple benefits of patient-generated health data in
      overcoming common barriers to self-management support in clinical practice and
      found the summary report feasible and usable in a clinical context.

PMID- 24876542
TI  - Short-Term Thermal-Humidity Shock Affects Point-of-Care Glucose Testing:
      Implications for Health Professionals and Patients.
AB  - The objective was to assess the effects of short-term (<=1 hour) static high
      temperature and humidity stresses on the performance of point-of-care (POC)
      glucose test strips and meters. Glucose meters are used by medical responders and
      patients in a variety of settings including hospitals, clinics, homes, and the
      field. Reagent test strips and instruments are potentially exposed to austere
      environmental conditions. Glucose test strips and meters were exposed to a mean
      relative humidity of 83.0% (SD = 8.0%) and temperature of 42 degrees C (107.6
      degrees F, SD = 3.2) in a Tenney BTRC environmental chamber. Stressed and
      unstressed glucose reagent strips and meters were tested with spiked blood
      samples (n = 40 measurements per time point for each of 4 trials) after 15, 30,
      45, and 60 minutes of exposure. Wilcoxon's signed rank test was applied to
      compare measurements test strip and meter measurements to isolate and
      characterize the magnitude of meter versus test strip effects individually.
      Stressed POC meters and test strips produced elevated glucose results, with
      stressed meter bias as high as 20 mg/dL (17.7% error), and stressed test strip
      bias as high as 13 mg/dL (12.2% error). The aggregate stress effect on meter and
      test strips yielded a positive bias as high as 33 mg/dL (30.1% error) after 15
      minutes of exposure. Short-term exposure (15 minutes) to high temperature and
      humidity can significantly affect the performance of POC glucose test strips and
      meters, with measurement biases that potentially affect clinical decision making
      and patient safety.

PMID- 24876543
TI  - Feasibility of Factory Calibration for Subcutaneous Glucose Sensors in Subjects
      With Diabetes.
AB  - BACKGROUND: Continuous glucose monitoring using subcutaneously inserted sensors
      currently requires blood glucose tests for sensor calibration. Alternatively,
      sensors precalibrated during the manufacturing process may eliminate the need for
      fingerstick calibrations. In this study we evaluated the feasibility of sensor
      factory calibration in subjects with diabetes. METHODS: A total of 33 subjects
      with diabetes were asked to wear 4 sensors in parallel, 2 on the arm and 2 on the
      abdomen. Sensors from a lot with low in vitro sensitivity coefficient of
      variation were used in the study. Based on frequent capillary blood glucose
      measurements, the average glucose sensitivity of each sensor was determined over
      a 5-day wear time. The in vivo sensitivities were analyzed for inter- and
      intrasubject variation. Mean absolute relative difference (MARD) calculation and
      consensus error grid analysis (EGA) were performed using a single calibration
      factor for all sensors, to simulate factory calibration and compared against
      conventional finger-stick calibration. RESULTS: The sensitivity coefficient of
      variation between sensors increased from 2.9% in vitro to 6.0% in vivo. No
      difference in sensor response between subjects (P = .069) as well as between
      insertion sites (arm and abdomen) was detected (P = .104). Applying one
      calibration factor to all sensors in the study resulted in an MARD of 13.4%, and
      83.5% of the values fell in consensus EGA zone A. Multiple fingerstick
      calibration resulted in an MARD of 12.7% and 84.1% in zone A. CONCLUSIONS:
      Feasibility of factory calibration was demonstrated in subjects with diabetes
      using sensors based on "wired enzyme" technology, resulting in accuracy metrics
      similar to sensors calibrated with capillary blood glucose.

PMID- 24876544
TI  - Validity and Reliability of a Glucometer Against Industry Reference Standards.
AB  - As an appealing alternative to reference glucose analyzers, portable glucometers
      are recommended for self-monitoring at home, in the field, and in research
      settings. The purpose was to characterize the accuracy and precision, and bias of
      glucometers in biomedical research. Fifteen young (20-36 years; mean = 24.5),
      moderately to highly active men (n = 10) and women (n = 5), defined by exercising
      2 to 3 times a week for the past 6 months, were given an oral glucose tolerance
      test (OGTT) after an overnight fast. Participants ingested 50, 75, or 150 grams
      of glucose over a 5-minute period. The glucometer was compared to a reference
      instrument. The glucometer had 39% of values within 15% of measurements made
      using the reference instrument ranging from 45.05 to 169.37 mg/dl. There was both
      a proportional (-0.45 to -0.39) and small fixed (5.06 and 0.90 mg/dl) bias.
      Results of the present study suggest that the glucometer provided poor validity
      and reliability results compared to the results provided by the reference
      laboratory analyzer. The portable glucometers should be used for patient
      management, but not for diagnosis, treatment, or research purposes.

PMID- 24876545
TI  - Glucose Measurement by Affinity Sensor and Pulsed Measurements of Fluidic
      Resistances: Proof of Principle.
AB  - Affinity sensors for glucose are based on a different measuring principle than
      the commercially available amperometric needle type sensors: reversible affinity
      interaction of glucose with specific receptors is the primary recognition
      mechanism instead of an enzymatic glucose oxidation. A novel pulsed-flow micro
      fluidic system was used to characterize first the viscosity of a sensitive liquid
      containing the glucose receptor Concanavalin A and dextran and in a second
      approach to characterize the geometry of a fluidic resistance. In the viscometric
      sensor, glucose of the sensitive liquid is equilibrated, while passing through a
      dialysis chamber, with the surrounding medium. With the membrane flow sensor, the
      viscosity of the liquid remains constant but the pores of the flow-resisting
      membrane contain a swellable hydrogel affecting the width of the pores. Two types
      of hydrogel were tested with the membrane flow sensor; one is highly sensitive to
      pH and salt concentration, the other contains receptors of phenyl boronic acids
      to obtain sensitivity to glucose. The viscometric affinity sensor (first
      approach) showed a linear response over 0 to 30 mmol/L glucose concentration
      range. The disturbing effect of air bubbles could be compensated for. The sensing
      proof of principle of the second approach could be demonstrated by its linear
      response to different saline concentrations; however, the glucose-sensitive
      membrane developed showed only a small response to glucose. Glucose monitoring
      based on this pulsed flow measuring principle offers interesting alternatives for
      the development of CGM systems with different options for the glucose sensing
      part.

PMID- 24876546
TI  - A Disposable Tear Glucose Biosensor-Part 4: Preliminary Animal Model Study
      Assessing Efficacy, Safety, and Feasibility.
AB  - OBJECTIVE: A prototype tear glucose (TG) sensor was tested in New Zealand white
      rabbits to assess eye irritation, blood glucose (BG) and TG lag time, and
      correlation with BG. METHODS: A total of 4 animals were used. Eye irritation was
      monitored by Lissamine green dye and analyzed using image analysis software. Lag
      time was correlated with an oral glucose load while recording TG and BG readings.
      Correlation between TG and BG were plotted against one another to form a
      correlation diagram, using a Yellow Springs Instrument (YSI) and self-monitoring
      of blood glucose as the reference measurements. Finally, TG levels were
      calculated using analytically derived expressions. RESULTS: From repeated testing
      carried over the course of 12 months, little to no eye irritation was detected.
      TG fluctuations over time visually appeared to trace the same pattern as BG with
      an average lag times of 13 minutes. TG levels calculated from the device current
      measurements ranged from 4 to 20 mg/dL and correlated linearly with BG levels of
      75-160 mg/dL (TG = 0.1723 BG = 7.9448 mg/dL; R2 = .7544). CONCLUSION: The first
      steps were taken toward preliminary development of a sensor for self-monitoring
      of tear glucose (SMTG). No conjunctival irritation in any of the animals was
      noted. Lag time between TG and BG was found to be noticeable, but a quantitative
      modeling to correlate lag time in this study is unnecessary. Measured currents
      from the sensors and the calculated TG showed promising correlation to BG levels.
      Previous analytical bench marking showed BG and TG levels consistent with other
      literature.

PMID- 24876547
TI  - Evaluation of an Algorithm for Retrospective Hypoglycemia Detection Using
      Professional Continuous Glucose Monitoring Data.
AB  - BACKGROUND: People with type 1 diabetes (T1D) are unable to produce insulin and
      thus rely on exogenous supply to lower their blood glucose. Studies have shown
      that intensive insulin therapy reduces the risk of late-diabetic complications by
      lowering average blood glucose. However, the therapy leads to increased incidence
      of hypoglycemia. Although inaccurate, professional continuous glucose monitoring
      (PCGM) can be used to identify hypoglycemic events, which can be useful for
      adjusting glucose-regulating factors. New pattern classification approaches based
      on identifying hypoglycemic events through retrospective analysis of PCGM data
      have shown promising results. The aim of this study was to evaluate a new pattern
      classification approach by comparing the performance with a newly developed PCGM
      calibration algorithm. METHODS: Ten male subjects with T1D were recruited and
      monitored with PCGM and self-monitoring blood glucose during insulin-induced
      hypoglycemia. A total of 19 hypoglycemic events occurred during the sessions.
      RESULTS: The pattern classification algorithm detected 19/19 hypoglycemic events
      with 1 false positive, while the PCGM with the new calibration algorithm detected
      17/19 events with 2 false positives. CONCLUSIONS: We can conclude that even after
      the introduction of new calibration algorithms, the pattern classification
      approach is still a valuable addition for improving retrospective hypoglycemia
      detection using PCGM.

PMID- 24876549
TI  - A Multicenter, Prospective, Randomized, Double-blind Study to Evaluate the Safety
      and Efficacy of Saroglitazar 2 and 4 mg Compared to Pioglitazone 45 mg in
      Diabetic Dyslipidemia (PRESS V).
AB  - Dual PPARalpha/gamma can improve both metabolic effects and minimized the side
      effects caused by either PPARalpha or PPARgamma agonist. The PRESS V study was
      aimed to evaluate the safety, tolerability, and efficacy of saroglitazar 2 mg and
      4 mg capsules (LipaglynTM; Zydus Code: ZYH1) as compared to high dose
      pioglitazone in patients with diabetic dyslipidemia. In this 26-week double
      blind, parallel arm, phase 3 study patients with hypertriglyceridemia with type 2
      diabetes mellitus (BMI > 23 kg/m2; hypertriglyceridemia: TG > 200 to 400 mg/dL;
      glycosylated hemoglobin [HbA1c] >7 to 9%) were enrolled from 14 sites in India.
      After 2 weeks of lifestyle modification, 122 patients were randomized double
      blind to 24-week treatment with the study drugs (saroglitazar 2 mg or 4 mg or
      pioglitazone 45 mg once daily) in a 1:1:1 ratio. The primary end point was change
      in plasma triglyceride level at week 24. The secondary end points were change in
      lipid profile and fasting plasma glucose at week 24. Patients who received study
      medication and had undergone at least 1 postbaseline efficacy evaluation were
      included in the efficacy analysis. All randomized patients who received at least
      a single dose were included for safety evaluation. The efficacy analysis included
      109 patients (n = 37 in saroglitazar 2 mg; n = 39 in saroglitazar 4 mg; n = 33 in
      pioglitazone). Saroglitazar 2 mg and 4 mg significantly reduced (P < .001) plasma
      triglyceride from baseline by 26.4% (absolute change +/- SD: -78.2 +/- 81.98
      mg/dL) and 45% (absolute change +/- SD -115.4 +/- 68.11 mg/dL), respectively, as
      compared to pioglitazone -15.5% (absolute change +/- SD: -33.3 +/- 162.41 mg/dL)
      at week 24. Saroglitazar 4 mg treatment also demonstrated marked decrease in low
      density lipoprotein (5%), very-low-density lipoprotein (45.5%), total cholesterol
      (7.7%), and apolipoprotein-B (10.9%). Saroglitazar treatment was generally safe
      and well tolerated. No serious adverse events were reported in saroglitazar
      treatment arm and no persistent change in laboratory parameters. Saroglitazar
      appeared to be an effective and safe therapeutic option for improving
      hypertriglyceridemia in patients with type 2 diabetes mellitus.

PMID- 24876550
TI  - Recommendations for Insulin Dose Calculator Risk Management.
AB  - Several studies have shown the usefulness of an automated insulin dose bolus
      advisor (BA) in achieving improved glycemic control for insulin-using diabetes
      patients. Although regulatory agencies have approved several BAs over the past
      decades, these devices are not standardized in their approach to dosage
      calculation and include many features that may introduce risk to patients.
      Moreover, there is no single standard of care for diabetes worldwide and no
      guidance documents for BAs, specifically. Given the emerging and more stringent
      regulations on software used in medical devices, the approval process is becoming
      more difficult for manufacturers to navigate, with some manufacturers opting to
      remove BAs from their products altogether. A comprehensive literature search was
      performed, including publications discussing: diabetes BA use and benefit,
      infusion pump safety and regulation, regulatory submissions, novel BAs, and
      recommendations for regulation and risk management of BAs. Also included were
      country-specific and international guidance documents for medical device,
      infusion pump, medical software, and mobile medical application risk management
      and regulation. No definitive worldwide guidance exists regarding risk management
      requirements for BAs, specifically. However, local and international guidance
      documents for medical devices, infusion pumps, and medical device software offer
      guidance that can be applied to this technology. In addition, risk management
      exercises that are algorithm-specific can help prepare manufacturers for
      regulatory submissions. This article discusses key issues relevant to BA use and
      safety, and recommends risk management activities incorporating current research
      and guidance.

PMID- 24876548
TI  - Comparative Assessment of Lixisenatide, Exenatide, and Liraglutide Pen Devices: A
      Pilot User-Based Study.
AB  - BACKGROUND: Glucagon-like peptide-1 (GLP-1) receptor agonists are a relatively
      recent addition to the treatment options for type 2 diabetes mellitus (T2DM) and
      are administered using prefilled pen devices. METHOD: In this open-label task and
      interview-based pilot study, 3 GLP-1 receptor agonist pen devices-exenatide
      (Byetta(r), Bristol-Myers Squibb/AstraZeneca), liraglutide (Victoza(r), Novo
      Nordisk), and lixisenatide (Lyxumia(r), Sanofi-Aventis)-were comparatively
      assessed in a randomized order in 30 participants with T2DM for ease of use,
      using a series of key performance measures (time taken to complete a series of
      tasks, number of user errors [successful performance], and user satisfaction
      rating). Linear and logistic regression analysis was conducted for the
      lixisenatide and liraglutide pens versus the exenatide pen. Participants' mean
      age was 60 years; 27% and 20% of the participants had visual impairments and
      reduced manual dexterity, respectively. RESULTS: Tasks were completed faster (P <
      .001) and with higher successful performance (P = .001) with the lixisenatide pen
      than with the exenatide pen, whereas the liraglutide pen was not statistically
      significant versus the exenatide pen on these parameters. Overall, user
      satisfaction was statistically higher for the lixisenatide and liraglutide pens
      versus the exenatide pen (P < .001 for both). CONCLUSIONS: Lixisenatide and
      liraglutide pens are associated with higher user satisfaction compared with the
      exenatide pen. In addition, the lixisenatide pen is faster and results in fewer
      errors than its comparator (exenatide). The lixisenatide pen may therefore be a
      suitable choice for patients with T2DM, including older and pen device-naive
      patients, and those with visual impairments and reduced manual dexterity.

PMID- 24876551
TI  - Does Device Make Any Difference? A Real-world Retrospective Study of Insulin
      Treatment Among Elderly Patients With Type 2 Diabetes.
AB  - We compared real-world clinical and economic outcomes for insulin glargine
      treatment administered by disposable pen and traditional vial-and-syringe
      injections among elderly patients with type 2 diabetes mellitus (T2DM). Using a
      large database of US retirees, this retrospective longitudinal study examined 1
      year follow-up outcomes in patients with T2DM aged 65 years or older who were
      either insulin naive and initiated insulin glargine via disposable pen (pen
      initiators [PI]) or vial (vial initiators [VI]) or were already insulin glargine
      users but either continued with a vial (vial continuers [VC]) or switched to a
      disposable pen (pen switchers [PS]). There were 7856 propensity-score-matched
      patients, including 2930 each in the PI and VI cohorts, and 998 each in the VC
      and PS cohorts. Compared with vial-and-syringe users, the disposable pen users
      had significantly greater treatment persistence (P < .0001 for both comparisons),
      duration of persistence (P < .0001 for both), and adherence (P < .01 for both)
      and lower insulin daily average consumption (P < .05 for both). Compared with the
      VI cohort, the PI cohort had significantly fewer hypoglycemia-related events (P =
      .0164). Total health care costs were comparable for the respective matched
      cohorts. In elderly patients with T2DM receiving insulin glargine therapy,
      initiating or switching to a disposable pen was associated with better treatment
      persistence and adherence than initiating or continuing with vial-and-syringe,
      without increased total health care costs. Among insulin-naive patients,
      initiating insulin glargine by disposable pen was also associated with
      significantly reduced risk of hypoglycemia compared with vial-and-syringe
      patients.

PMID- 24876553
TI  - Confusion Regarding Duration of Insulin Action: A Potential Source for Major
      Insulin Dose Errors by Bolus Calculators.
AB  - People with diabetes on insulin pumps often use a bolus calculator (BC) to obtain
      insulin dose recommendations. After the first bolus of the day, residual insulin
      activity, called bolus insulin on board (BOB), must be correctly accounted for to
      reduce the size of subsequent boluses and minimize the insulin stacking that
      would otherwise occur. Critical to achieving this calculation is having an
      appropriate duration of insulin action (DIA) setting in the BC. Unfortunately,
      the widespread use of inappropriately short DIAs may be causing unrecognized
      "stacking" of insulin that leads to unexplained hypoglycemic events. Currently,
      there is no widely accepted definition or value of the DIA for use in a BC.
      Various shortcomings regarding the selection of an appropriate DIA setting have
      led to considerable confusion among clinicians and insulin pump users about this
      important concept. Traditional pharmacological studies used to determine the
      pharmacodynamic (PD) properties of rapid-acting insulins create a misleading
      impression that insulin action times (IATs) in daily life vary from 3 to 5 hours
      and cause IATs to appear more variable than they actually are. These IAT time
      ranges are not appropriate for use as the DIA time value required to obtain an
      accurate bolus recommendation from a BC. We highlight the problems that arise
      when an inappropriately short DIA leads to excessive bolus recommendations,
      provide a research protocol to accurately measure DIA, and suggest appropriate
      DIA time recommendations for use in current clinical practice.

PMID- 24876554
TI  - Impact of Biosimilar Insulins on Clinical Practice: Meeting Report.
AB  - The availability of biosimilar insulins can potentially lead to lower insulin
      costs and increased access for patients with diabetes, worldwide. However,
      clinicians and regulatory agencies have raised several concerns regarding the
      safety and efficacy of these new medications. The European regulatory agencies
      have established guidelines for market approval of biosimilar insulins; however,
      many issues remain unresolved. Moreover, although the FDA has developed
      preliminary pathways for biosimilar protein development and is prepared to review
      each application on a case-by-case basis, insulins do not fall under this pathway
      at this time. The development of effective postmarketing surveillance protocols,
      determination of product interchangeability, and product identification/labeling
      remain key concerns. Numerous issues surround the development and
      commercialization of biosimilar insulins; thus, it is important that all
      stakeholders fully understand the complexity of these issues and how they can
      potentially affect patient care. Bridging the educational gap among clinicians
      and regulatory agencies will be challenging but necessary for ensuring patient
      safety.

PMID- 24876555
TI  - Reimbursement for Diabetes Medical Devices in Germany.

PMID- 24876552
TI  - Extracellular Matrix Scaffold Technology for Bioartificial Pancreas Engineering:
      State of the Art and Future Challenges.
AB  - Emergent technologies in regenerative medicine may soon overcome the limitations
      of conventional diabetes therapies. Collaborative efforts across the subfields of
      stem cell technology, islet encapsulation, and biomaterial carriers seek to
      produce a bioengineered pancreas capable of restoring endocrine function in
      patients with insulin-dependent diabetes. These technologies rely on a robust
      understanding of the extracellular matrix (ECM), the supportive 3-dimensional
      network of proteins necessary for cellular attachment, proliferation, and
      differentiation. Although these functions can be partially approximated by
      biosynthetic carriers, novel decellularization protocols have allowed researchers
      to discover the advantages afforded by the native pancreatic ECM. The native ECM
      has proven to be an optimal platform for recellularization and whole-organ
      pancreas bioengineering, an exciting new field with the potential to resolve the
      dire shortage of transplantable organs. This review seeks to contextualize recent
      findings, discuss current research goals, and identify future challenges of
      regenerative medicine as it applies to diabetes management.

PMID- 24876556
TI  - Use of a Smart Glucose Monitoring System to Guide Insulin Dosing in Patients With
      Diabetes in Regular Clinical Practice.

PMID- 24876557
TI  - Use of Real-Time Continuous Glucose Monitoring in Patients on Insulin Pump
      Therapy: Real-Life Experience in an Endocrinology Office.

PMID- 24876558
TI  - Accessibility of Insulin Pump Displays to People With Low Vision.

PMID- 24876559
TI  - Evaluation of the Performance of a Novel Five-Level A1c Cellular Linearity
      Calibration Verification Kit.

PMID- 24876560
TI  - Plasminogen promotes macrophage phagocytosis in mice.
AB  - The phagocytic function of macrophages plays a pivotal role in eliminating
      apoptotic cells and invading pathogens. Evidence implicating plasminogen (Plg),
      the zymogen of plasmin, in phagocytosis is extremely limited with the most recent
      in vitro study showing that plasmin acts on prey cells rather than on
      macrophages. Here, we use apoptotic thymocytes and immunoglobulin opsonized
      bodies to show that Plg exerts a profound effect on macrophage-mediated
      phagocytosis in vitro and in vivo. Plg enhanced the uptake of these prey by
      J774A.1 macrophage-like cells by 3.5- to fivefold Plg receptors and plasmin
      proteolytic activity were required for phagocytosis of both preys. Compared with
      Plg(+/+) mice, Plg(-/-) mice exhibited a 60% delay in clearance of apoptotic
      thymocytes by spleen and an 85% reduction in uptake by peritoneal macrophages.
      Phagocytosis of antibody-mediated erythrocyte clearance by liver Kupffer cells
      was reduced by 90% in Plg(-/-) mice compared with Plg(+/+) mice. A gene array of
      splenic and hepatic tissues from Plg(-/-) and Plg(+/+) mice showed downregulation
      of numerous genes in Plg(-/-) mice involved in phagocytosis and regulation of
      phagocytic gene expression was confirmed in macrophage-like cells. Thus, Plg may
      play an important role in innate immunity by changing expression of genes that
      contribute to phagocytosis. 

PMID- 24876561
TI  - Diagnostic and risk criteria for HSCT-associated thrombotic microangiopathy: a
      study in children and young adults.
AB  - Transplant-associated thrombotic microangiopathy (TMA) leads to generalized
      endothelial dysfunction that can progress to multiorgan injury, and severe cases
      are associated with poor outcomes after hematopoietic stem cell transplantation
      (HSCT). Identifying patients at highest risk for severe disease is challenging.
      We prospectively evaluated 100 consecutive HSCT recipients to determine the
      incidence of moderate and severe TMA and factors associated with poor overall
      outcomes. Thirty-nine subjects (39%) met previously published criteria for TMA.
      Subjects with TMA had a significantly higher nonrelapse mortality (43.6% vs 7.8%,
      P < .0001) at 1 year post-HSCT compared with those without TMA. Elevated lactate
      dehydrogenase, proteinuria on routine urinalysis, and hypertension were the
      earliest markers of TMA. Proteinuria (>30 mg/dL) and evidence of terminal
      complement activation (elevated sC5b-9) in the blood at the time of TMA diagnosis
      were associated with very poor survival (<20% at 1 year), whereas all TMA
      subjects without proteinuria and a normal sC5b-9 serum concentration survived (P
      < .01). Based on these prospective observations, we conclude that severe TMA
      occurred in 18% of HSCT recipients in our cohort and propose an algorithm to
      identify the highest-risk patients who might benefit from prompt clinical
      interventions. 

PMID- 24876562
TI  - Chemokine treatment rescues profound T-lineage progenitor homing defect after
      bone marrow transplant conditioning in mice.
AB  - Development of T cells in the thymus requires continuous importation of T-lineage
      progenitors from the bone marrow via the circulation. Following bone marrow
      transplant, recovery of a normal peripheral T-cell pool depends on production of
      naive T cells in the thymus; however, delivery of progenitors to the thymus
      limits T-lineage reconstitution. Here, we examine homing of intravenously
      delivered progenitors to the thymus following irradiation and bone marrow
      reconstitution. Surprisingly, following host conditioning by irradiation, we find
      that homing of lymphoid-primed multipotent progenitors and common lymphoid
      progenitors to the thymus decreases more than 10-fold relative to unirradiated
      mice. The reduction in thymic homing in irradiated mice is accompanied by a
      significant reduction in CCL25, an important chemokine ligand for thymic homing.
      We show that pretreatment of bone marrow progenitors with CCL25 and CCL21
      corrects the defect in thymic homing after irradiation and promotes thymic
      reconstitution. These data suggest new therapeutic approaches to promote T-cell
      regeneration. 

PMID- 24876563
TI  - Current concepts in the diagnosis and management of cytokine release syndrome.
AB  - As immune-based therapies for cancer become potent, more effective, and more
      widely available, optimal management of their unique toxicities becomes
      increasingly important. Cytokine release syndrome (CRS) is a potentially life
      threatening toxicity that has been observed following administration of natural
      and bispecific antibodies and, more recently, following adoptive T-cell therapies
      for cancer. CRS is associated with elevated circulating levels of several
      cytokines including interleukin (IL)-6 and interferon gamma, and uncontrolled
      studies demonstrate that immunosuppression using tocilizumab, an anti-IL-6
      receptor antibody, with or without corticosteroids, can reverse the syndrome.
      However, because early and aggressive immunosuppression could limit the efficacy
      of the immunotherapy, current approaches seek to limit administration of
      immunosuppressive therapy to patients at risk for life-threatening consequences
      of the syndrome. This report presents a novel system to grade the severity of CRS
      in individual patients and a treatment algorithm for management of CRS based on
      severity. The goal of our approach is to maximize the chance for therapeutic
      benefit from the immunotherapy while minimizing the risk for life threatening
      complications of CRS. 

PMID- 24876564
TI  - Multiparameter flow cytometry for staging of solitary bone plasmacytoma: new
      criteria for risk of progression to myeloma.
AB  - Solitary plasmacytoma represents a heterogeneous group of patients; approximately
      half develop multiple myeloma (MM) in 2 or 3 years, whereas others remain disease
      free at 10 years. By definition, these patients do not have morphologic bone
      marrow (BM) plasma cell (PC) infiltration. Here, we investigated whether
      sensitive BM evaluation of patients with solitary bone plasmacytoma (SBP; n = 35)
      and extramedullary plasmacytoma (EMP; n = 29) through multiparameter flow
      cytometry (MFC) would unravel the presence of clonal PCs in otherwise disease
      free BM, and whether BM clonality predicted higher risk of progression. BM clonal
      PCs were detected in 17 of 35 SBP (49%) and 11 of 29 EMP (38%) patients. Seventy
      one percent of flow-positive vs only 8% of flow-negative SBP patients evolved to
      MM (median time to progression of 26 months vs not reached; hazard ratio, 17.4; P
      < .001). No significant differences were observed among EMP cases. Our results
      highlight the importance of MFC for sensitive BM evaluation of SBP patients, to
      predict risk of developing treatment-requiring MM and to plan disease monitoring.

PMID- 24876565
TI  - Molecular liaisons between erythropoiesis and iron metabolism.
AB  - Although most circulating iron in blood plasma is destined for erythropoiesis,
      the mechanisms by which erythropoietic demand modulates the iron supply
      ("erythroid regulators") remain largely unknown. Iron absorption, plasma iron
      concentrations, and tissue iron distribution are tightly controlled by the liver
      produced hormone hepcidin. During the last decade, much progress has been made in
      elucidating hepcidin regulation by iron and inflammation. This review discusses
      the less understood mechanisms and mediators of hepcidin suppression in
      physiologically and pathologically stimulated erythropoiesis. 

PMID- 24876567
TI  - We Need More Research and Better Designs for Insulin Infusion Sets.

PMID- 24876566
TI  - Failure-free survival after initial systemic treatment of chronic graft-versus
      host disease.
AB  - This study was designed to characterize failure-free survival (FFS) as a novel
      end point for clinical trials of chronic graft-versus-host disease (GVHD). The
      study cohort included 400 consecutive patients who received initial systemic
      treatment of chronic GVHD at our center. FFS was defined by the absence of second
      line treatment, nonrelapse mortality, and recurrent malignancy during initial
      treatment. The FFS rate was 68% at 6 months and 54% at 12 months after initial
      treatment. Multivariate analysis identified 4 risk factors associated with
      treatment failure: time interval <12 months from transplantation to initial
      treatment, patient age >=60 years, severe involvement of the gastrointestinal
      tract, liver, or lungs, and Karnofsky score <80% at initial treatment. Initial
      steroid doses and the type of initial treatment were not associated with risk of
      treatment failure. Lower steroid doses after 12 months of initial treatment were
      associated with long-term success in withdrawing all systemic treatment. FFS
      offers a potentially useful basis for interpreting results of initial treatment
      of chronic GVHD. Incorporation of steroid doses at 12 months would increase
      clinical benefit associated with the end point. Studies using FFS as the primary
      end point should measure changes in GVHD-related symptoms, activity, damage, and
      disability as secondary end points. 

PMID- 24876568
TI  - Comparative Study of the Routine Daily Usability of FoodLog: A Smartphone-based
      Food Recording Tool Assisted by Image Retrieval.
AB  - The health care field is focusing considerable attention on dietary control,
      which requires that individuals record what they eat. We have developed a novel
      smartphone application called FoodLog, a multimedia food recording tool that
      allows users to take photos of their meals and to produce textual food records.
      Unlike conventional smartphone-based food recording tools, FoodLog allows users
      to employ meal photos to help them to input textual descriptions based on image
      retrieval. In this study, we conducted usability experiments to evaluate the
      routine daily use of FoodLog systems with and without image-based assistance. We
      produced 2 food recording tools: FoodLog with image-based assistance (FL-I) and
      FoodLog with text input only (FL-T). We recruited 18 university students (age =
      18-24 years), all of whom performed food recording for the first time. The
      participants used FoodLog on a daily basis for 1 month. In the subjective
      evaluation, FL-I had higher average scores for questions related to ease of use,
      fun, frequency of browsing, and intention to continue. In particular, the latter
      3 factors received significantly higher scores with FL-I than with FL-T. In the
      quantitative evaluation, the daily average number of meal events and food records
      did not differ significantly between FL-I and FL-T. A detailed analysis of the
      individual records showed that 1 participant produced 3 times as many records
      using FL-I compared with FL-T. The subjective assessment showed that our new
      tool, which fully exploits the use of images, is a promising method for food
      recording.

PMID- 24876569
TI  - DialBetics: A Novel Smartphone-based Self-management Support System for Type 2
      Diabetes Patients.
AB  - Numerous diabetes-management systems and programs for improving glycemic control
      to meet guideline targets have been proposed, using IT technology. But all of
      them allow only limited-or no-real-time interaction between patients and the
      system in terms of system response to patient input; few studies have effectively
      assessed the systems' usability and feasibility to determine how well patients
      understand and can adopt the technology involved. DialBetics is composed of 4
      modules: (1) data transmission module, (2) evaluation module, (3) communication
      module, and (4) dietary evaluation module. A 3-month randomized study was
      designed to assess the safety and usability of a remote health-data monitoring
      system, and especially its impact on modifying patient lifestyles to improve
      diabetes self-management and, thus, clinical outcomes. Fifty-four type 2 diabetes
      patients were randomly divided into 2 groups, 27 in the DialBetics group and 27
      in the non-DialBetics control group. HbA1c and fasting blood sugar (FBS) values
      declined significantly in the DialBetics group: HbA1c decreased an average of
      0.4% (from 7.1 +/- 1.0% to 6.7 +/- 0.7%) compared with an average increase of
      0.1% in the non-DialBetics group (from 7.0 +/- 0.9% to 7.1 +/- 1.1%) (P = .015);
      The DialBetics group FBS decreased an average of 5.5 mg/dl compared with a non
      DialBetics group average increase of 16.9 mg/dl (P = .019). BMI improvement
      although not statistically significant because of the small sample size-was
      greater in the DialBetics group. DialBetics was shown to be a feasible and an
      effective tool for improving HbA1c by providing patients with real-time support
      based on their measurements and inputs.

PMID- 24876570
TI  - Monitoring Artificial Pancreas Trials Through Agent-based Technologies: A Case
      Report.
AB  - The increase in the availability and reliability of network connections lets
      envision systems supporting a continuous remote monitoring of clinical parameters
      useful either for overseeing chronic diseases or for following clinical trials
      involving outpatients. We report here the results achieved by a telemedicine
      infrastructure that has been linked to an artificial pancreas platform and used
      during a trial of the AP@home project, funded by the European Union. The
      telemedicine infrastructure is based on a multiagent paradigm and is able to
      deliver to the clinic any information concerning the patient status and the
      operation of the artificial pancreas. A web application has also been developed,
      so that the clinic staff and the researchers involved in the design of the blood
      glucose control algorithms are able to follow the ongoing experiments. Albeit the
      duration of the experiments in the trial discussed in the article was limited to
      only 2 days, the system proved to be successful for monitoring patients, in
      particular overnight when the patients are sleeping. Based on that outcome we can
      conclude that the infrastructure is suitable for the purpose of accomplishing an
      intelligent monitoring of an artificial pancreas either during longer trials or
      whenever that system will be used as a routine treatment.

PMID- 24876571
TI  - Assessment of Patient Perceptions About Web Telemonitoring Applied to Artificial
      Pancreas Use at Home.
AB  - Patients with chronic diseases as well as health care systems could benefit from
      telemedicine applications such as remote monitoring (RM). RM relies on a device
      that sends patients' health data to a remote server accessible by care teams.
      Recent smartphone-based artificial pancreas (AP) systems collect comprehensive
      set of information and could therefore support the development of RM applied to
      diabetes. To better understand how RM could be integrated in future AP systems,
      we wanted to get patients' opinion on this concept, as they are the final users
      of these systems. An online questionnaire with 11 items was sent to 20
      experienced patients who tested AP and RM during our recent outpatient studies in
      France and Italy. We received 17 answers. All patients considered that during
      their participation in trials, RM was useful, reassuring, and essential. One
      third wouldn't have participated without it. When AP is commercialized, 88% of
      respondents think that AP should go with a RM tool, but it should be activated
      only at certain times, at first use or in case of difficulties (82%).
      Participants ask for technical support when a device fails (88%) and for medical
      help in case of prolonged hyperglycemia (65%) or severe or repeated hypoglycemia
      (53%), but not after each case of hypoglycemia (6%). More than 75% think that RM
      could help them to improve their blood glucose control. This preliminary work
      indicates that patients expect RM to be part of future AP development. Larger
      studies remain to be performed to investigate its usefulness and potential
      economic effectiveness.

PMID- 24876572
TI  - Differences Between Patients With Type 2 Diabetes Mellitus Interested and
      Uninterested in the Use of a Patient Platform (e-VitaDM-2/ZODIAC-41).
AB  - The prevalence of type 2 diabetes mellitus (T2DM) is rising in the Netherlands,
      and health care's workload will increase. e-Health applications may increase
      patients' participation in their care and could help reducing workload. To
      explore potential users, differences in patients interested and uninterested in e
      Health are characterized. A prospective cohort study was initiated in the Drenthe
      region of the Netherlands. This study included inviting T2DM patients to use e
      Health (the e-Vita platform). Patients were offered access to clinical data,
      laboratory results, educational modules, and a self-management support program.
      Data were obtained from health record systems of general practices and
      questionnaires. Out of 2674 patients, 1378 (51.5%) participated in the study. Of
      the 1378 patients, 974 (70.7%) were interested in e-Health. Of 974, 405 (41.6%)
      were registered for e-Health. Interested patients were more often male, were
      younger, had shorter T2DM duration, and were higher educated. Of 405, 110 (27.2%)
      used the e-Health. No differences were found between users and nonusers of e
      Health. Patients interested in e-Health were more often male, were younger, had
      shorter T2DM duration, and were more often higher educated. However, even in this
      interested group, the actual participation rate remained low. Together with
      characteristics and attitudes of caregivers and T2DM patients, the look and
      content of the e-Health platform strategies that increase interest and
      participation need to be developed.

PMID- 24876573
TI  - Patient-oriented Computerized Clinical Guidelines for Mobile Decision Support in
      Gestational Diabetes.
AB  - The risks associated with gestational diabetes (GD) can be reduced with an active
      treatment able to improve glycemic control. Advances in mobile health can provide
      new patient-centric models for GD to create personalized health care services,
      increase patient independence and improve patients' self-management capabilities,
      and potentially improve their treatment compliance. In these models, decision
      support functions play an essential role. The telemedicine system MobiGuide
      provides personalized medical decision support for GD patients that is based on
      computerized clinical guidelines and adapted to a mobile environment. The
      patient's access to the system is supported by a smartphone-based application
      that enhances the efficiency and ease of use of the system. We formalized the GD
      guideline into a computer-interpretable guideline (CIG). We identified several
      workflows that provide decision-support functionalities to patients and 4 types
      of personalized advice to be delivered through a mobile application at home,
      which is a preliminary step to providing decision-support tools in a telemedicine
      system: (1) therapy, to help patients to comply with medical prescriptions; (2)
      monitoring, to help patients to comply with monitoring instructions; (3) clinical
      assessment, to inform patients about their health conditions; and (4) upcoming
      events, to deal with patients' personal context or special events. The whole
      process to specify patient-oriented decision support functionalities ensures that
      it is based on the knowledge contained in the GD clinical guideline and thus
      follows evidence-based recommendations but at the same time is patient-oriented,
      which could enhance clinical outcomes and patients' acceptance of the whole
      system.

PMID- 24876574
TI  - The Added Value of Log File Analyses of the Use of a Personal Health Record for
      Patients With Type 2 Diabetes Mellitus: Preliminary Results.
AB  - The electronic personal health record (PHR) is a promising technology for
      improving the quality of chronic disease management. Until now, evaluations of
      such systems have provided only little insight into why a particular outcome
      occurred. The aim of this study is to gain insight into the navigation process
      (what functionalities are used, and in what sequence) of e-Vita, a PHR for
      patients with type 2 diabetes mellitus (T2DM), to increase the efficiency of the
      system and improve the long-term adherence. Log data of the first visits in the
      first 6 weeks after the release of a renewed version of e-Vita were analyzed to
      identify the usage patterns that emerge when users explore a new application.
      After receiving the invitation, 28% of all registered users visited e-Vita. In
      total, 70 unique usage patterns could be identified. When users visited the
      education service first, 93% of all users ended their session. Most users visited
      either 1 or 5 or more services during their first session, but the distribution
      of the routes was diffuse. In conclusion, log file analyses can provide valuable
      prompts for improving the system design of a PHR. In this way, the match between
      the system and its users and the long-term adherence has the potential to
      increase.

PMID- 24876575
TI  - Tele-diabetology to Screen for Diabetes and Associated Complications in Rural
      India: The Chunampet Rural Diabetes Prevention Project Model.
AB  - Diabetes, with its acute and long-term complications, has become a major health
      hazard in developing countries. An estimated 62.4 million people in India have
      diabetes. With increasing urbanization and industrialization, we can expect huge
      numbers of people with diabetes in India in the future. Moreover, all diabetes
      efforts in India are currently focused in urban areas while 70% of India's
      population actually lives in rural areas. The current statistics demonstrates
      that urgent interventions are mandatory to curb the epidemic of diabetes and its
      complications at the grassroots level. This gap in providing diabetes care can be
      nullified by the use of tele-diabetology. This holds great potential to overcome
      barriers and improve quality and access to diabetes care to remote, underserved
      areas of developing counties. The Chunampet Rural Diabetes Prevention Project
      (CRDPP) has been developed and tested as a successful model for screening and
      delivering diabetes care to rural areas in developing countries. Using a tele
      diabetology mobile van loaded with appropriate equipment, trained technicians,
      and satellite technology helped us to screen for diabetes and its complications
      and deliver diabetes care to remote villages in southern India. The Chunampet
      model can be applied in reaching out to remote areas where specialized diabetes
      care facilities may not be available.

PMID- 24876576
TI  - Teleophthalmology in Diabetic Retinopathy.
AB  - Over the past decade, there have been rapid strides in progress in the fields of
      telecommunication and medical imaging. There is growing evidence regarding use of
      teleophthalmology for screening of diabetic retinopathy. This article highlights
      some pertinent questions regarding use of telescreening for diabetic retinopathy.
      It deals with evidence regarding accuracy of diagnosis, patients satisfaction and
      cost-effectiveness. The American Telemedicine Association have given certain
      guidelines for teleheath practices for diabetic retinopathy. The article
      discusses regarding these guidelines. Finally, a working model for diabetic
      retinopathy screening through teleophthalmology has been described. Telescreening
      for diabetic retinopathy seems to be a cost-effective, accurate, and reliable
      method for screening for diabetic retinopathy. The American Telemedicine
      Association has set up guidelines for telescreening that should be adhered to
      provide quality screening services to people with diabetes.

PMID- 24876577
TI  - Evaluating the Performance of a Novel Embedded Closed-loop System.
AB  - The objective was to assess the reliability of a novel automated closed-loop
      glucose control system developed within the AP@home consortium in adults with
      type 1 diabetes. Eight adults with type 1 diabetes on insulin pump therapy (3
      men; ages 40.5 +/- 14.3 years; HbA1c 8.2 +/- 0.8%) participated in an open-label,
      single-center, single-arm, 12-hour overnight study performed at the clinical
      research facility. A standardized evening meal (80 g CHO) accompanied by prandial
      insulin boluses were given at 19:00 followed by an optional snack of 15 g at
      22:00 without insulin bolus. Automated closed-loop glucose control was started at
      19:00 and continued until 07:00 the next day. Basal insulin delivery (Accu-Chek
      Spirit, Roche) was automatically adjusted by Cambridge model predictive control
      algorithm, running on a purpose-built embedded device, based on real-time
      continuous glucose monitor readings (Dexcom G4 Platinum). Closed-loop system was
      operational as intended over 99% of the time. Overnight plasma glucose levels
      (22:00 to 07:00) were within the target range (3.9 to 8.0 mmol/l) for 75.4%
      (37.5, 92.9) of the time without any time spent in hypoglycemia (<3.9 mmol/l).
      Mean overnight glucose was 7.8 +/- 1.3 mmol/l. For the entire 12-hour closed-loop
      period (19:00 until 07:00) plasma glucose levels were within the target range
      (3.9 to 10.0 mmol/l) for 84.4% (63.3, 100) of time. There were no adverse events
      noted during the trial. We observed a high degree of reliability of the automated
      closed-loop system. The time spent in target glucose level overnight was
      comparable to results of previously published studies. Further developments to
      miniaturize the system for home studies are warranted.

PMID- 24876578
TI  - The Minimum Duration of Sensor Data From Which Glycemic Variability Can Be
      Consistently Assessed.
AB  - Despite much discussion regarding the clinical relevance of glycemic variation
      (GV), little discourse has addressed the properties of the data set from which it
      is derived. We aimed to assess the minimum duration of data required using
      continuous glucose monitoring (CGM) that most closely approximates to a gold
      standard 90-day measure. Data from 20 children and adolescents with type 1
      diabetes were examined. All participants had CGM data sets of 90 days duration,
      from which standard deviation (SD), coefficient of variation (CV), mean amplitude
      of glycemic action (MAGE), and continuous overlapping net glycemic action (CONGA1
      8) were calculated for the overall period and then investigational periods of 2,
      4, 6, 12, 18, 24, and 30 days. The percentage difference between each measure and
      the overall measure per time period was assessed. As the duration of the CGM data
      set increased, the percentage error continued to decrease, giving a metric
      approximating more closely toward the overall measure. Median SD and CV differed
      from the overall measure by <10% at 12 days duration. The frequency of
      interruptions to the CGM trace rendered MAGE and CONGA unreliable, hence SD and
      CV were reported. We suggest that data sets used to infer GV should be of a
      minimum duration of 12 days. MAGE and CONGA exhibit poor performance in the
      setting of frequent trace interruption.

PMID- 24876579
TI  - The Association of Glucose Variability and Home Discharge Among Survivors of
      Critical Illness Managed With a Computerized Decision-Support Tool for Glycemic
      Control.
AB  - In-intensive care unit (ICU) glucose variability (GV) is associated with
      increased mortality. However, the impact of GV on hospital survivors' morbidity
      and associated changes in destination at time of hospital discharge are unknown.
      We studied a retrospective patient cohort in a medical/surgical ICU, requiring
      insulin infusion, using computer-guided insulin dosing software. Standard
      deviation (GluSD) and coefficient of variation (GluCV) were used as GV measures.
      We examined rates of home discharge (H) in the whole cohort and selected
      subgroups across GV quartiles, between patients with and without H, determinants
      of H, and determinants of GV and its association with patients' ICU length of
      stay (LOS). A total of 351 patients met study criteria. The association of GV and
      H varied among examined subgroups. H increased with GV quartile (GluSD; P =
      .004). GV was higher in patients with H than non-H (GluSD 36.1 vs 30.0 mg/dl,
      respectively; P = .002). Increased GV was not a predictor of reduced H on
      multivariate analysis. GV was inversely associated with patients' ICU LOS in all
      examined subgroups. Increased number of hypoglycemic events and time to attain
      target glycemia were independent predictors of reduced H. GV was not associated
      with adverse impact on H in the present cohort, and its prognostic impact should
      be considered in the context of ICU LOS of examined patient populations. Further
      studies are needed to examine the morbidity effects of GV and other glycemia
      related measures among hospital survivors of critical illness across varying ICU
      populations, glycemic control approaches, and glycemic targets.

PMID- 24876580
TI  - Differences in Glycemic Variability Between Normoglycemic and Prediabetic
      Subjects.
AB  - So far the criteria for NGT and abnormal glucose tolerance (AGT) are based on
      HbA1c and 75 g oGTT. We present data on GV and diurnal profiles in stratified
      cohorts with AGT versus controls. 28 NGT, 42 AGT (15 IGT, 11 IFG, 16 CGI) matched
      for age and BMI classified by 75 g oGTT underwent a CGM with test meal (TM).
      Diurnal profiles, glucose excursion after TM, and GV (SD, MAGE) were calculated
      for day 2 and 3. HbA1c, with its values of 5.5 +/- 0.37% versus 5.65 +/- 0.36%,
      was within normal range. Average interstitial glucose (AiG) was 5.84 +/- 0.52
      mmol/l) in NGT and 6.35 +/- 0.65 mmol/l in AGT (P = .002). The 2 h incremental
      area under curve (iAUC) from TM until 2 h after TM was 1.94 +/- 1.31 mmol/l*h
      versus 2.89 ( +/- 1.75) mmol/l*h (P = .012), AiG 2 hours after TM was 5.99 +/-
      1.14 mmol/l*d versus 6.64 +/- 1.30 mmol/l (P = .035). Peaks of AiG after TM were
      7.69 +/- 1.48 mmol/l*d versus 9.18 +/- 1.67 mmol/l*d (P = .001). SD was
      significantly higher for AGT (1.12 +/- 0.37 vs. 0.85 +/- 0.32 mmol/l, P = .01)
      and MAGE 2.26 +/- 0.84 vs. 1.60 +/- 0.69 mmol/l, P = .005). In this comparative
      analysis NGT and AGT well matched for age, BMI, and comorbidities, CGM revealed
      significant differences in daytime AiG, pp glucose excursion and postprandial
      peaks. SD and MAGE was significantly higher for subjects with AGT. I Impaired
      glucose homeostasis a better characterizes degree of AGTe than HbA1c and 75 g
      OGTT.

PMID- 24876581
TI  - Passive Diffusion of Transdermal Glucose: Noninvasive Glucose Sensing Using a
      Fluorescent Glucose Binding Protein.
AB  - The motivation for this study was to determine if a statistically significant
      correlation exists between blood glucose (BG) and transdermal glucose (TG)
      collected by passive diffusion. A positive outcome will indicate that noninvasive
      passive TG diffusion is a painless alternative to collecting blood through a
      break on the skin. Sampling involves placing a small volume of buffer solution on
      the surface of membrane or skin for 5 minutes. The sample is then assayed with
      fluorescent GBP. In vitro testing was done on regenerated cellulose and a porcine
      skin model to determine diffusion of standard glucose solutions. In vivo testing
      was done on a healthy subject and a subject with type 2 diabetes. Glucose
      diffused readily through the regenerated cellulose membrane with good correlation
      between surface and internal glucose concentrations (R 2 = .997). But the porcine
      skin model required a surface prewash to achieve the same good correlation R 2 =
      .943). Based on this, an optimum prewash step was determined for the in vivo
      studies. The resulting correlation coefficients between TG and BG after a 15
      minute prewash in a healthy subject and type 2 subject were .87 and .93,
      respectively. Removal of the extraneous glucose in the skin by prewashing was an
      important step in achieving good correlation between TG and BG. The results
      suggest that passive collection of TG is a noninvasive alternative to current
      practice of breaking the skin. Further studies are under way to determine the lag
      time between TG and BG and for the sampling protocol to be more amenable to point
      of-care application.

PMID- 24876582
TI  - "Glucose-at-a-Glance": New Method to Visualize the Dynamics of Continuous Glucose
      Monitoring Data.
AB  - The standard continuous glucose monitoring (CGM) output provides multiple
      graphical and numerical summaries. A useful adjunct would be a visualization tool
      that facilitates immediate assessment of both long- and short-term variability.
      We developed an algorithm based on the mathematical method of delay maps to
      display CGM signals in which the glucose value at time ti is plotted against its
      value at time ti+1. The data points are then color-coded based on their frequency
      of occurrence (density). Examples of this new visualization tool, along with the
      accompanying time series, are presented for selected patients with type 2
      diabetes and non-diabetic controls over the age of 70 years. The method reveals
      differences in the structure of the glucose variability between subjects with a
      similar range of glucose values. We also observe that patients with comparable
      hemoglobin A1c (HbA1c) values may have very different delay maps, consistent with
      marked differences in the dynamics of glucose control. These differences are not
      accounted by the amplitude of the fluctuations. Furthermore, the delay maps allow
      for rapid recognition of hypo- and hyperglycemic periods over the full duration
      of monitoring or any subinterval. The glucose-at-a-glance visualization tool,
      based on colorized delay maps, provides a way to quickly assess the complex data
      acquired by CGM systems. This method yields dynamical information not contained
      in single summary statistics, such as HbA1c values, and may also serve as the
      basis for developing novel metrics of glycemic control.

PMID- 24876583
TI  - Design of the Glucose Rate Increase Detector: A Meal Detection Module for the
      Health Monitoring System.
AB  - The Glucose Rate Increase Detector (GRID), a module of the Health Monitoring
      System (HMS), has been designed to operate in parallel to the glucose controller
      to detect meal events and safely trigger a meal bolus. The GRID algorithm was
      tuned on clinical data with 40-70 g CHO meals and tested on simulation data with
      50-100 g CHO meals. Active closed- and open-loop protocols were executed in
      silico with various treatments, including automatic boluses based on a 75 g CHO
      meal and boluses based on simulated user input of meal size. An optional function
      was used to reduce the recommended bolus using recent insulin and glucose
      history. For closed-loop control of a 3-meal scenario (50, 75, and 100 g CHO),
      the GRID improved median time in the 80-180 mg/dL range by 17% and in the >180
      range by 14% over unannounced meals, using an automatic bolus for a 75 g CHO meal
      at detection. Under open-loop control of a 75 g CHO meal, the GRID shifted the
      median glucose peak down by 73 mg/dL and earlier by 120 min and reduced the time
      >180 mg/dL by 57% over a missed-meal bolus scenario, using a full meal bolus at
      detection. The GRID improved closed-loop control in the presence of large meals,
      without increasing late postprandial hypoglycemia. Users of basal-bolus therapy
      could also benefit from GRID as a safety alert for missed meal corrections.

PMID- 24876584
TI  - Predicting Plasma Glucose From Interstitial Glucose Observations Using Bayesian
      Methods.
AB  - One way of constructing a control algorithm for an artificial pancreas is to
      identify a model capable of predicting plasma glucose (PG) from interstitial
      glucose (IG) observations. Stochastic differential equations (SDEs) make it
      possible to account both for the unknown influence of the continuous glucose
      monitor (CGM) and for unknown physiological influences. Combined with prior
      knowledge about the measurement devices, this approach can be used to obtain a
      robust predictive model. A stochastic-differential-equation-based gray box (SDE
      GB) model is formulated on the basis of an identifiable physiological model of
      the glucoregulatory system for type 1 diabetes mellitus (T1DM) patients. A
      Bayesian method is used to estimate robust parameters from clinical data. The
      models are then used to predict PG from IG observations from 2 separate study
      occasions on the same patient. First, all statistically significant diffusion
      terms of the model are identified using likelihood ratio tests, yielding
      inclusion of [Formula: see text], [Formula: see text], and [Formula: see text].
      Second, estimates using maximum likelihood are obtained, but prediction
      capability is poor. Finally a Bayesian method is implemented. Using this method
      the identified models are able to predict PG using only IG observations. These
      predictions are assessed visually. We are also able to validate these estimates
      on a separate data set from the same patient. This study shows that SDE-GBs and a
      Bayesian method can be used to identify a reliable model for prediction of PG
      using IG observations obtained with a CGM. The model could eventually be used in
      an artificial pancreas.

PMID- 24876585
TI  - Personalized State-space Modeling of Glucose Dynamics for Type 1 Diabetes Using
      Continuously Monitored Glucose, Insulin Dose, and Meal Intake: An Extended Kalman
      Filter Approach.
AB  - An essential component of any artificial pancreas is on the prediction of blood
      glucose levels as a function of exogenous and endogenous perturbations such as
      insulin dose, meal intake, and physical activity and emotional tone under natural
      living conditions. In this article, we present a new data-driven state-space
      dynamic model with time-varying coefficients that are used to explicitly quantify
      the time-varying patient-specific effects of insulin dose and meal intake on
      blood glucose fluctuations. Using the 3-variate time series of glucose level,
      insulin dose, and meal intake of an individual type 1 diabetic subject, we apply
      an extended Kalman filter (EKF) to estimate time-varying coefficients of the
      patient-specific state-space model. We evaluate our empirical modeling using (1)
      the FDA-approved UVa/Padova simulator with 30 virtual patients and (2) clinical
      data of 5 type 1 diabetic patients under natural living conditions. Compared to a
      forgetting-factor-based recursive ARX model of the same order, the EKF model
      predictions have higher fit, and significantly better temporal gain and J index
      and thus are superior in early detection of upward and downward trends in
      glucose. The EKF based state-space model developed in this article is
      particularly suitable for model-based state-feedback control designs since the
      Kalman filter estimates the state variable of the glucose dynamics based on the
      measured glucose time series. In addition, since the model parameters are
      estimated in real time, this model is also suitable for adaptive control.

PMID- 24876586
TI  - Negative Pressure Wound Therapy With Low Pressure and Gauze Dressings to Treat
      Diabetic Foot Wounds.
AB  - This study was a prospective cohort study to evaluate negative pressure wound
      therapy (NPWT) with low pressure and a gauze dressing to treat diabetic foot
      wounds. Thirty patients with diabetic foot wounds were consented to a prospective
      study to evaluate wound closure and complications to evaluate NPWT with low
      pressure (80 mmHg) and a gauze dressing interface (EZCare, Smith and Nephew) for
      up to 5 weeks. NPWT was changed 3 times a week. Study subjects were evaluated
      once a week for adverse events and wound measurements. Of study subjects, 43%
      attained at least a 50% wound area reduction after 4 weeks of therapy. Our
      results suggest that a high rate of wound closure could be expected with low
      pressure and a gauze interface.

PMID- 24876587
TI  - Detection of 1,5-Anhydroglucitol by Electrochemical Impedance Spectroscopy.
AB  - Multiple markers are used to assess glycemic control in patients with diabetes
      mellitus (DM). New technology that permits simultaneous detection of multiple
      biomarkers combined with those used at the point of care indicative of glycemic
      control, including glycemic variability determined from 1,5-anhydroglucitol
      measurement, could provide better management and further insight into the
      disease. This platform was based on previous research involving glucose detection
      and uses electrochemical impedance spectroscopy to detect a range of 1,5
      anhydroglucitol concentrations at an optimal binding frequency. The enzyme
      pyranose oxidase was fixed to gold electrodes while a sine wave of sweeping
      frequencies was induced in purified solutions and in variable presence of whole
      blood. The optimal binding frequency for the detection of 1,5-anhydroglucitol was
      found to be 3.71 kHz. The impedance response compared to the concentration of
      target present was found to have a logarithmic slope of 7.04 with an R-squared
      value of 0.96. This response includes 2 experimental sets, a single test of a low
      concentration range and a high concentration range with 5 replicates. The
      relative standard deviation of the high range varied from 28% to 27% from lowest
      to highest concentrations. Best detection in complex solutions was found in lower
      blood concentrations of 0.5% and 1%, but maintained relatively high accuracy in
      concentrations 5% and 10%. The sensor platform was successfully evaluated at a
      high dynamic range of 1,5-AG in purified solutions. In the presence of whole
      blood, lowest percentages yielded the best results indicating that filtering
      interferents may be necessary in final device architecture.

PMID- 24876588
TI  - Retinal Microcirculation in Type 1 Diabetic Patients With and Without Peripheral
      Sensory Neuropathy.
AB  - In patients with diabetes mellitus (DM), early retinal microvascular alterations
      can be observed even before the clinical diagnosis of diabetic retinopathy. This
      study aimed to investigate morphological and functional changes in retinal
      microvascular blood flow in type 1 diabetic patients with and without peripheral
      neuropathy (PNP) as compared to nondiabetic controls. Retinal microvascular blood
      flow (RBF) was assessed using scanning laser Doppler flowmetry (Heidelberg Retina
      Flowmeter, Heidelberg Engineering, Germany) before and after stimulation with
      flicker light. PNP was assessed using the neuropathy disability score (NDS) and
      by the evaluation of the vibration perception threshold (VPT). A total of 41
      subjects were recruited for study participation and were stratified to 3
      different groups according to their metabolic and neurological status: 14
      nondiabetic subjects without PNP, 14 diabetic patients without PNP, and 13
      diabetic patients with PNP. All subjects were free from diabetic retinopathy as
      assessed by fundoscopy. In diabetic patients with PNP, baseline and stimulated
      RBF was higher compared with diabetic patients without PNP and the nondiabetic
      control group. No difference with regard to RBF could be observed between the
      nondiabetic control subjects and patients with type 1 DM without PNP. No
      difference in the arterial WLR could be observed between the 3 groups. A linear
      correlation was found for VPT and RBF (r = .38, P < .001) and for NDS and RBF (r
      = .44, P < .0001). In our study population of patients with type 1 diabetes, PNP
      was associated with functional but not morphological changes in RBF.

PMID- 24876589
TI  - Mobile Diabetes Intervention for Glycemic Control: Impact on Physician
      Prescribing.
AB  - Of adults with type 2 diabetes, 84% take antihyperglycemic medication. Successful
      treatment requires active monitoring and medication dose adjustment by health
      providers. The objective of this study was to determine how a mobile-phone-based
      coaching system for diabetes management influences physician prescribing
      behavior. This secondary data analysis is based on a cluster randomized clinical
      trial that reported patients provided with mobile self-management had reduction
      in glycated hemoglobin (HbA1c) of 1.9% over 1 year, compared to 0.7% in control
      patients (P < .001). Participants were primary care patients with type 2 diabetes
      randomized at physician practice level into a control group (n = 55) and
      intervention group (n = 62). Main study measures were patients' medication
      records (medication, dose, frequency, start and end date) abstracted at baseline
      and study end. Antihyperglycemic medications, including sulfonylureas or
      thiazolidinediones, and antihypertensive and antilipemic medications were
      analyzed. A higher percentage of patients in the intervention group had
      modification and intensification of incretin mimetics during the 1-year study
      period (9.7% vs 0.0% and 8.1% vs 0.0%, both P = .008). A higher percentage of
      patients in the intervention group had modification and intensification of
      metformin (24.2% vs 7.3%, P = .033). The overall difference in physician
      prescribing of oral antihyperglycemic medications was not statistically
      significant. Our results suggest mobile diabetes interventions can encourage
      physicians to modify and intensify antihyperglycemic medications in patients with
      type 2 diabetes. Differences in physician prescribing behavior were modest, and
      do not appear to be large enough to explain a 1.2% decrease in HbA1c.

PMID- 24876590
TI  - Changes in Insulin Requirements From the Onset of Continuous Subcutaneous Insulin
      Infusion (CSII) Until Optimization of Glycemic Control.
AB  - The aim was to evaluate changes in insulin requirements from onset of continuous
      subcutaneous insulin infusion (CSII) until glucose optimization in type 1
      diabetes and to determine patient characteristics to be considered when CSII is
      implemented. We retrospectively analyzed 74 type 1 diabetic patients over a
      follow-up of 5 months after starting CSII. Patients without a decrease in HbA1c
      levels at the end of follow-up were excluded. We compared total daily doses
      (TDD), basal/bolus distribution, basal diurnal/nocturnal proportion, number of
      basal segments, and HbA1c levels in relation to sex, age, body mass index (BMI),
      diabetes duration, and indication for CSII. At follow-up, HbA1c decreased by
      0.75%, TDD decreased by 18%, basal rate was 60% of TDD, and diurnal basal rate
      was 60% of total basal rate. Insulin requirements were higher in males and in
      obese patients. Female patients and patients with longer diabetes duration showed
      a higher percentage of basal insulin. The number of basal segments was 4.9 +/-
      2.9. Basal requirements were higher in the second half of the nocturnal period.
      The dawn phenomenon was more relevant in men. Improvements in glycemic control
      were more marked in younger patients, in patients with higher HbA1c, in patients
      using more basal segments, and in patients initiating CSII for glucose control
      before pregnancy. Sex, diabetes duration, and BMI should be considered when
      initiating CSII. Our findings may help clinicians in clinical decision making
      regarding CSII therapy.

PMID- 24876592
TI  - Current Trends in Continuous Glucose Monitoring.
AB  - The market introduction of systems for continuous glucose monitoring (CGM) some
      15 years ago did not immediately revolutionize the treatment of diabetes;
      however, for a given group of patients, it would almost be inconceivable nowadays
      to imagine life without CGM. One day the development of insulin pumps together
      with CGM could culminate in an artificial pancreas system. The performance of the
      glucose sensors used for glucose measurement in the interstitial fluid in the
      subcutaneous tissue and the algorithms employed to analyze these data have
      improved so much over the past decade that current CGM systems by far outperform
      those of the first generations. This commentary discusses a number of aspects
      about what we have learned since CGM systems entered the market and what current
      trends exist in their usage. Some of these are major hurdles facing a more
      widespread usage of CGM.

PMID- 24876593
TI  - What Are the Next Steps in Continuous Glucose Monitoring?
AB  - The development of glucose sensors for continuous glucose monitoring (CGM) is
      likely still in its early days. A number of novel approaches-along with many
      attempts to improve current CGM systems-are in development. The next generation
      of glucose sensors (NGGS) will also enable, for example, reliable glucose
      measurement in the low glycemic range. NGGS systems represent an important step
      forward for closed-loop systems. This commentary discusses a number of aspects
      that are relevant in this context.

PMID- 24876591
TI  - Telehealth Remote Monitoring Systematic Review: Structured Self-monitoring of
      Blood Glucose and Impact on A1C.
AB  - The aim was to summarize research on telehealth remote patient monitoring
      interventions that incorporate key elements of structured self-monitoring of
      blood glucose (SMBG) identified as essential for improving A1C. A systematic
      review was conducted using the Medline, Cumulative Index to Nursing and Allied
      Health Literature, EMBASE, and OVID Medline databases with search terms
      "Telemedicine" AND "Monitoring, Physiologic" AND "Diabetes Mellitus, Type 2."
      Study selection criteria included original randomized clinical trials evaluating
      the impact of telehealth remote patient monitoring on A1C among adults with type
      2 diabetes and incorporated 1 or more essential elements of SMBG identified by
      the International Diabetes Federation (patient education, provider education,
      structured SMBG profile, SMBG goals, feedback, data used to modify treatment,
      interactive communication or shared decision making). Fifteen studies were
      included, with interventions ranging from 3 to 12 months (mean 8 months) with
      sample sizes from 30 to 1665. Key SMBG elements were grouped into 3 categories:
      education, SMBG protocols, and feedback. Research incorporating 5 of the 7
      elements consistently achieved significant A1C improvements between study groups.
      Interventions using more SMBG elements are associated with an improvement in A1C.
      Studies with the largest A1C decrease incorporated 6 of the 7 elements and
      computer decision support. Two studies with 5 of the 7 elements and active
      medication management achieved significant A1C decreases. Telehealth remote
      patient monitoring interventions in type 2 diabetes have not included all
      structured monitoring elements recommended by the IDF. Incorporating more
      elements of structured SMBG is associated with improved A1C.

PMID- 24876596
TI  - The Danger of Using Total Error Models to Compare Glucose Meter Performance.
AB  - Glucose meter performance specifications provide limits for 95% of results, which
      is the same as total error. A popular total error model is that total error
      equals (average) bias plus 2 times imprecision. This model has been used to
      specify combinations of average bias and imprecision that satisfy total error
      goals. But this model is incomplete and its conclusions are suspect. It is shown
      that when interferences occur in glucose meters as exemplified by hematocrit
      interference, the total error model proposed by Boyd and Bruns cannot distinguish
      between meters that differ in performance. The CLSI standard EP21-A, does not
      have this problem because it directly estimates total error bypassing the need
      for a model. An example illustrates these points.

PMID- 24876595
TI  - Biologic Basis of Nerve Decompression Surgery for Focal Entrapments in Diabetic
      Peripheral Neuropathy.
AB  - The most recent (2011) National Diabetes Fact Sheet states the combined diagnosed
      and undiagnosed number of diabetes cases in the United States is approaching 25
      million, and another 79 million are prediabetic. Of the diabetes patients, 60-70%
      suffer from mild to severe neuropathy. This combined loss of sensory and motor
      control in diabetic limbs is usually considered an irreversible, progressive
      process. Patients suffering from these losses are at a significantly higher risk
      for development of foot ulceration, frequently leading to infection and partial
      or major limb amputation. However, a review of focal nerve entrapment surgical
      decompression literature suggests that several diabetic sensorimotor
      polyneuropathy (DSPN) symptoms and complications are potentially partially
      reversible or preventable. Decompression surgery represents a paradigm shift in
      treatment protocols because it both relieves pain and restores protective
      sensation, while providing significant protection against a cascade of serious
      foot complications. This review surveys current research regarding the biological
      basis for diabetic focal entrapment neuropathy. Metabolic dysfunction related to
      aldose reductase, oxidative stress, and advanced glycation end products are
      considered and correlated to peripheral nerve enlargement and entrapment. In
      addition, observational studies correlated to that biological basis are presented
      as well as surgical outcomes illustrating the effect of decompression on DSPN
      symptomatic relief, nerve function, and protection against complications.

PMID- 24876597
TI  - Accuracy Evaluation of Three Systems for Self-monitoring of Blood Glucose With
      Three Different Test Strip Lots Following ISO 15197.

PMID- 24876594
TI  - Nanomaterial-mediated Biosensors for Monitoring Glucose.
AB  - Real-time monitoring of physiological glucose transport is crucial for gaining
      new understanding of diabetes. Many techniques and equipment currently exist for
      measuring glucose, but these techniques are limited by complexity of the
      measurement, requirement of bulky equipment, and low temporal/spatial resolution.
      The development of various types of biosensors (eg, electrochemical, optical
      sensors) for laboratory and/or clinical applications will provide new insights
      into the cause(s) and possible treatments of diabetes. State-of-the-art
      biosensors are improved by incorporating catalytic nanomaterials such as carbon
      nanotubes, graphene, electrospun nanofibers, and quantum dots. These
      nanomaterials greatly enhance biosensor performance, namely sensitivity, response
      time, and limit of detection. A wide range of new biosensors that incorporate
      nanomaterials such as lab-on-chip and nanosensor devices are currently being
      developed for in vivo and in vitro glucose sensing. These real-time monitoring
      tools represent a powerful diagnostic and monitoring tool for measuring glucose
      in diabetes research and point of care diagnostics. However, concerns over the
      possible toxicity of some nanomaterials limit the application of these devices
      for in vivo sensing. This review provides a general overview of the state of the
      art in nanomaterial-mediated biosensors for in vivo and in vitro glucose sensing,
      and discusses some of the challenges associated with nanomaterial toxicity.

PMID- 24876598
TI  - Efficacy and Safety of Continuous Insulin Infusion Protocols With Glycemic
      Targets of 110-140 mg/dL in Patients With and Without Diabetes Following Cardiac
      Surgery.

PMID- 24876599
TI  - Basal Insulin Use in the Non-Critical Care Setting: Is Fasting Hypoglycemia
      Inevitable or Preventable?

PMID- 24876600
TI  - Blood Glucose Test Strip Utilization Within Medicare.

PMID- 24876601
TI  - Diurnal Heart Rate Variability Fluctuations in Normal Volunteers.

PMID- 24876602
TI  - Analytical Evaluation of the Xpress and Hospital Blood Glucose Monitoring
      Systems.

PMID- 24876603
TI  - ADAG study group data links A1C levels with empirically measured blood glucose
      values - new treatment guidelines will now be needed.

PMID- 24876604
TI  - Effect of force of microneedle insertion on the permeability of insulin in skin.
AB  - Many experiments conducted in the literature have investigated the effect of
      microneedles (MNs) on insulin permeation across skin. There are also a number of
      articles that deal with the effect of MN insertion force in skin. However, there
      is little known on quantifying the relationship between the effect of MN
      insertion force and the amount of insulin permeated for given MNs. This issue is
      addressed in this article. MNs of 1100 um and 1400 um are used to conduct in
      vitro permeability experiments on porcine skin, using insulin. Histological
      images of MN treated skin are obtained from a microtome and the viscoelastic
      properties of the skin sample are measured using a rheometer. An in-house
      insertion force device is utilized that can reproducibly apply a specified force
      on MNs for a set period of time using compressed air. It is deduced that when
      porcine skin was pretreated with an applied force of 60.5 N and 69.1 N, the
      resultant amount of insulin permeated was approximately 3 ug and 25 ug over a 4
      hour period for the MNs used. The amount of MN force applied to porcine skin was
      shown to be related to the amount of insulin permeated. An increase in insertion
      force increase the amount of insulin permeated. It was also demonstrated that
      using insufficient force may have reduced or prevented the amount of insulin
      passing through the skin, regardless of the geometry of the MNs. 

PMID- 24876605
TI  - Intradermal insulin delivery: a promising future for diabetes management.
AB  - The incidence of insulinopenic diabetes mellitus is constantly increasing, and in
      addition, approximately a third of all hyperinsulinemic diabetic patients develop
      insulinopenia. Optimal glycemic control is essential to minimize the risk for
      diabetes-induced complications, but the majority of diabetic patients fail to
      achieve proper long-term glucose levels even in clinical trials, and even more so
      in clinical practice. Compliance with a treatment regimen is likely to be higher
      if the procedure is simple, painless, and discreet. Thus, insulin has been
      suggested for nasal, gastrointestinal, and inhalation therapy, but so far with
      considerable downsides in effect, side effects, or patient acceptance. The
      stratum corneum is the main barrier preventing convenient drug administration
      without the drawbacks of subcutaneous injections. Recently, devices with
      miniaturized needles have been developed that combine the simplicity and
      discretion of patch-based treatments, but with the potential of peptide and
      protein administration. As this review describes, initial comparisons with
      subcutaneous administration now suggest microneedle patches for active insulin
      delivery are efficient in maintaining glycemic control. Hollow microneedle
      technology could also prove to be efficient in systemic as well as local delivery
      of other macromolecular drugs, such as vaccines. 

PMID- 24876606
TI  - Oral insulin reloaded: a structured approach.
AB  - Optimal coverage of insulin needs is the paramount aim of insulin replacement
      therapy in patients with diabetes mellitus. To apply insulin without breaking the
      skin barrier by a needle and/or to allow a more physiological provision of
      insulin are the main reasons triggering the continuous search for alternative
      routes of insulin administration. Despite numerous attempts over the past 9
      decades to develop an insulin pill, no insulin for oral dosing is commercially
      available. By way of a structured approach, we aim to provide a systematic update
      on the most recent developments toward an orally available insulin formulation
      with a clear focus on data from clinical-experimental and clinical studies.
      Thirteen companies that claim to be working on oral insulin formulations were
      identified. However, only 6 of these companies published new clinical trial
      results within the past 5 years. Interestingly, these clinical data reports make
      up a mere 4% of the considerably high total number of publications on the
      development of oral insulin formulations within this time period. While this
      picture clearly reflects the rising research interest in orally bioavailable
      insulin formulations, it also highlights the fact that the lion's share of
      research efforts is still allocated to the preclinical stages. 

PMID- 24876607
TI  - Analytical performance of glucose monitoring systems at different blood glucose
      ranges and analysis of outliers in a clinical setting.
AB  - We investigated the analytical accuracy of 27 glucose monitoring systems (GMS) in
      a clinical setting, using the new ISO accuracy limits. In addition to measuring
      accuracy at blood glucose (BG) levels < 100 mg/dl and > 100 mg/dl, we also
      analyzed devices performance with respect to these criteria at 5 specific BG
      level ranges, making it possible to further differentiate between devices with
      regard to overall performance. Carbohydrate meals and insulin injections were
      used to induce an increase or decrease in BG levels in 37 insulin-dependent
      patients. Capillary blood samples were collected at 10-minute intervals, and BG
      levels determined simultaneously using GMS and a laboratory-based method. Results
      obtained via both methods were analyzed according to the new ISO criteria. Only
      12 of 27 devices tested met overall requirements of the new ISO accuracy limits.
      When accuracy was assessed at BG levels < 100 mg/dl and > 100 mg/dl, criteria
      were met by 14 and 13 devices, respectively. A more detailed analysis involving 5
      different BG level ranges revealed that 13 (48.1%) devices met the required
      criteria at BG levels between 50 and 150 mg/dl, whereas 19 (70.3%) met these
      criteria at BG levels above 250 mg/dl. The overall frequency of outliers was low.
      The assessment of analytical accuracy of GMS at a number of BG level ranges made
      it possible to further differentiate between devices with regard to overall
      performance, a process that is of particular importance given the user-centered
      nature of the devices' intended use. 

PMID- 24876608
TI  - Insulin pump patient characteristics and glucose control in the hospitalized
      setting.
AB  - Patients' knowledge of their insulin pumps and glucose control during
      hospitalization has not been studied. The aim was to study the determinants of
      glycemic control in patients using continuous subcutaneous insulin infusion
      (CSII) in the hospital. Three groups of patients were identified: those who did
      not need any inpatient education and continued on CSII (gorup A), those who
      received education then continued on CSII (group B), and those for whom CSII was
      not appropriate and were treated with multiple daily insulin injections (gorup
      C). We compared the measures of glycemic control between the 3 groups and
      analyzed which variables impacted glucose control. There were 50 patients, with
      51 hospital admissions, 57% males, mean age 48 +/- 13 years, 86% had type 1
      diabetes (T1DM). The mean DM duration was 26 +/- 14 years, mean duration of CSII
      use was 8.7 +/- 6 years, and mean HbA1c was 7.6 +/- 1.4%. The mean duration of
      hospital stay was 5.6 +/- 4.6 days. Mean blood glucose (BG) and frequency of
      hyperglycemia and hypoglycemic events among the 3 groups adjusted for their
      duration of hospital stay were not statistically different. None of the patients
      developed diabetic ketoacidosis while using their pump. Stepwise multivariate
      analysis revealed knowledge of hypoglycemia correction was the single most
      important predictor of mean BG (P < .001). Patients who received inpatient
      education performed similarly to patients who did not need inpatient education.
      Patients who receive inpatient education on CSII fare similar as patients who did
      not require inpatient education. 

PMID- 24876610
TI  - Design, development, and evaluation of a novel microneedle array-based continuous
      glucose monitor.
AB  - The development of accurate, minimally invasive continuous glucose monitoring
      (CGM) devices has been the subject of much work by several groups, as it is
      believed that a less invasive and more user-friendly device will result in
      greater adoption of CGM by persons with insulin-dependent diabetes. This article
      presents the results of preliminary clinical studies in subjects with diabetes of
      a novel prototype microneedle-based continuous glucose monitor. In this device,
      an array of tiny hollow microneedles is applied into the epidermis from where
      glucose in interstitial fluid (ISF) is transported via passive diffusion to an
      amperometric glucose sensor external to the body. Comparison of 1396 paired
      device glucose measurements and fingerstick blood glucose readings for up to 72
      hour wear in 10 diabetic subjects shows the device to be accurate and well
      tolerated by the subjects. Overall mean absolute relative difference (MARD) is
      15% with 98.4% of paired points in the A+B region of the Clarke error grid. The
      prototype device has demonstrated clinically accurate glucose readings over 72
      hours, the first time a microneedle-based device has achieved such performance. 

PMID- 24876609
TI  - Impact of a reduced error range of SMBG in insulin-treated patients in Germany.
AB  - Modeling approaches demonstrate that improvement in the accuracy of blood glucose
      (BG) meters may lead to cost savings. An improvement of accuracy of BG meters on
      the basis of a reduction in error range from 20% to 5% has been reported to be
      associated with substantial cost savings in Germany. The aim of this study is to
      analyze potential cost savings related to a reduction in error range from 20% to
      15% and 10% of glucose meters in Germany. The health economic analysis included
      the number of type 1 diabetic and the number of insulin-treated patients in
      Germany, the costs for glucose monitoring, a model on the effects of the
      improvement of accuracy on the impact of severe hypoglycemic episodes, HbA1c, and
      subsequently myocardial infarctions and the costs of diabetes-related
      complications in Germany. In the model, a reduction of 1% and 3.5% reduction in
      severe hypoglycemic episodes, and a 0.14% and 0.28% reduction in HbA1c was
      included. In type 1 diabetes the savings could be equal to a reduction in health
      care expenditures of more than ?1.0 million (20% vs 15% error range) and ?3.4
      million (20% vs 10% error range). Respectively, potential savings of more than
      ?6.0 million and ?20.1 million were calculated for the group of insulin-treated
      patients. The model demonstrates that a reduction of error range of BG meters
      from 20% to 15% and 10% may translate into substantial savings for the German
      health care system. 

PMID- 24876611
TI  - Continuous glucose monitors: use of waveform versus glycemic values in the
      improvements of glucose control, quality of life, and fear of hypoglycemia.
AB  - How patients are benefitting from continuous glucose monitoring (CGM) remains
      poorly understood. The focus on numerical glucose values persists, even though
      access to the glucose waveform and rate of change may contribute more to improved
      control. This pilot study compared outcomes of patients using CGMs with or
      without access to the numerical values on their CGM. Ten persons with type 1
      diabetes, naive to CGM use, enrolled in a 12-week study. Subjects were randomly
      assigned to either unmodified CGM receivers, or to CGM receivers that had their
      numerical values obscured but otherwise functioned normally. HbA1c, quality of
      life (QLI-D), and fear of hypoglycemia (HFS) were assessed, at baseline and at
      week 12. Baseline HbA1c for the entire group was 7.46 +/- 1.27%. At week 12 the
      experimental group HbA1c reduction was 1.5 +/- 0.9% (p < .05), the control
      group's reduction was 0.06 +/- 0.61% (p > .05). Repeated measures testing
      revealed no significant difference in HbA1c reduction between groups. Both groups
      had reductions in HFS; these reductions were statistically significant within
      groups (p < .05), but not between groups. QLI-D indices demonstrated improvements
      (p < .05) in QLI-D total and the health and family subscales, but not between
      groups. The results of this pilot study suggest that benefits of CGM extend
      beyond reductions in HbA1c to reductions in fear of hypoglycemia and improvements
      in quality of life. The display of a numerical glucose value did not improve
      control when compared to numerically blinded units. 

PMID- 24876612
TI  - Treatment recommendations following 3-day masked continuous glucose monitoring
      (CGM) in youth with type 1 diabetes.
AB  - Glycemic control remains suboptimal in youth with type 1 diabetes. Retrospective
      continuous glucose monitoring (CGM) has demonstrated utility in fine-tuning
      diabetes management by detecting postprandial hyperglycemia and hypoglycemia. In
      this study, we explored the process of 3-day masked CGM use, subsequent treatment
      recommendations, and impact on A1c in a clinic-based sample of youth with type 1
      diabetes. Over 2 years, 122 youth were referred for masked CGM. Patients/families
      completed a diary of blood glucose levels, insulin doses, food intake, and
      exercise during CGM use. A1c was assessed pre- and 2-3 months post-CGM. Treatment
      recommendations were formulated using data from CGM reports and diaries. Mean age
      was 14.3 +/- 3.9 years, diabetes duration was 7.5 +/- 4.7 years, and A1c was 8.5
      +/- 1.1% (69 +/- 12 mmol/mol); 61% were pump-treated. Patients received an
      average of 3.1 +/- 1.1 treatment recommendations following review of the CGM
      report. Most (80%) received reinforcement of the importance of preprandial
      bolusing; 37% received a recommendation regarding advanced insulin management
      (use of combination boluses/attend to active insulin). Receipt of the latter
      recommendation was related to A1c improvement >=0.5% (OR: 4.0, P < .001). Masked
      CGM offers opportunities to guide advanced insulin management (by injection or
      pump), which may yield A1c improvements in youth with type 1 diabetes. 

PMID- 24876613
TI  - An integrated multivariable artificial pancreas control system.
AB  - The objective was to develop a closed-loop (CL) artificial pancreas (AP) control
      system that uses continuous measurements of glucose concentration and
      physiological variables, integrated with a hypoglycemia early alarm module to
      regulate glucose concentration and prevent hypoglycemia. Eleven open-loop (OL)
      and 9 CL experiments were performed. A multivariable adaptive artificial pancreas
      (MAAP) system was used for the first 6 CL experiments. An integrated
      multivariable adaptive artificial pancreas (IMAAP) system consisting of MAAP
      augmented with a hypoglycemia early alarm system was used during the last 3 CL
      experiments. Glucose values and physical activity information were measured and
      transferred to the controller every 10 minutes and insulin suggestions were
      entered to the pump manually. All experiments were designed to be close to real
      life conditions. Severe hypoglycemic episodes were seen several times during the
      OL experiments. With the MAAP system, the occurrence of severe hypoglycemia was
      decreased significantly (P < .01). No hypoglycemia was seen with the IMAAP
      system. There was also a significant difference (P < .01) between OL and CL
      experiments with regard to percentage of glucose concentration (54% vs 58%) that
      remained within target range (70-180 mg/dl). Integration of an adaptive control
      and hypoglycemia early alarm system was able to keep glucose concentration values
      in target range in patients with type 1 diabetes. Postprandial hypoglycemia and
      exercise-induced hypoglycemia did not occur when this system was used. Physical
      activity information improved estimation of the blood glucose concentration and
      effectiveness of the control system. 

PMID- 24876614
TI  - Application of the reference method isotope dilution gas chromatography mass
      spectrometry (ID/GC/MS) to establish metrological traceability for calibration
      and control of blood glucose test systems.
AB  - Self-monitoring of blood glucose (BG) by means of handheld BG systems is a
      cornerstone in diabetes therapy. The aim of this article is to describe a
      procedure with proven traceability for calibration and evaluation of BG systems
      to guarantee reliable BG measurements. Isotope dilution gas chromatography mass
      spectrometry (ID/GC/MS) is a method that fulfills all requirements to be used in
      a higher-order reference measurement procedure. However, this method is not
      applicable for routine measurements because of the time-consuming sample
      preparation. A hexokinase method with perchloric acid (PCA) sample pretreatment
      is used in a measurement procedure for such purposes. This method is directly
      linked to the ID/GC/MS method by calibration with a glucose solution that has an
      ID/GC/MS-determined target value. BG systems are calibrated with whole blood
      samples. The glucose levels in such samples are analyzed by this ID/GC/MS-linked
      hexokinase method to establish traceability to higher-order reference material.
      For method comparison, the glucose concentrations in 577 whole blood samples were
      measured using the PCA-hexokinase method and the ID/GC/MS method; this resulted
      in a mean deviation of 0.1%. The mean deviation between BG levels measured in
      >500 valid whole blood samples with BG systems and the ID/GC/MS was 1.1%. BG
      systems allow a reliable glucose measurement if a true reference measurement
      procedure, with a noninterrupted traceability chain using ID/GC/MS linked
      hexokinase method for calibration of BG systems, is implemented. Systems should
      be calibrated by means of a traceable and defined measurement procedure to avoid
      bias. 

PMID- 24876615
TI  - The impact of continuous glucose monitoring on low interstitial glucose values
      and low blood glucose values assessed by point-of-care blood glucose meters:
      results of a crossover trial.
AB  - In a randomized crossover trial the impact of continuous glucose monitoring (CGM)
      was tested on the occurrence of low blood glucose values measured by point of
      care (POC) measurement and on low glucose values measured by CGM in the
      interstitial fluid. A total of 41 type 1 diabetic patients (age 42.0 +/- 11.4
      years, diabetes duration 15.3 +/- 10.1 years, A1c 8.2 +/- 1.4%) used a CGM system
      (Dexcom SEVEN PLUS system) twice. In first study phase (CGM blind), patients were
      blind regarding the CGM current glucose levels and were not alerted when critical
      glucose values were reached. In the second phase (CGM real time), patients had
      access to current glucose levels and were alerted if critical glucose values were
      reached. During CGM real time the proportion of hypoglycemic POC blood glucose
      values were significantly reduced (7.5 +/- 5.6% vs 10.1 +/- 7.5%; P = .04),
      whereas the proportion of euglycemic blood glucose values were significantly
      enhanced (73.7 +/- 18.3% vs 68.3 +/- 12.1%; P = .01). The duration of low glucose
      periods in the interstitial fluid was significantly lower in the CGM real time
      phase (125 +/- 89 vs 181 +/- 125 minutes per day; P = .005). The time until a low
      blood glucose was detected by POC measurement was shortened by 33.2 +/- 76.1
      minutes (P = .03). The study demonstrated that CGM is able to not only reduce
      duration of hypoglycemia measured by CGM in interstitial fluid, but also reduce
      the proportion of low POC blood glucose measurements. In addition, hypoglycemia
      can be detected earlier. 

PMID- 24876616
TI  - Lessons learned from a pilot RCT of simultaneous versus delayed initiation of
      continuous glucose monitoring in children and adolescents with type 1 diabetes
      starting insulin pump therapy.
AB  - Uncertainty remains about effectiveness of continuous glucose monitoring (CGM) in
      pediatric type 1 diabetes (T1D). Success with CGM is related to CGM adherence,
      which may relate to readiness to make the behavior changes required for effective
      use. We hypothesize that readiness for change will be greater at initiation of
      insulin pump therapy than in established pump users, and that this will predict
      CGM adherence. Our objective was to evaluate the feasibility of a randomized
      controlled trial (RCT) in children with established T1D comparing simultaneous
      pump and CGM initiation to standard pump therapy with delayed CGM initiation. We
      randomized participants to simultaneous pump and CGM initiation or to standard
      pump therapy with the option of adding CGM 4 months later. CGM adherence was
      tracked via web-based download and readiness for change assessed with the
      SOCRATES questionnaire. Of 41 eligible children, 20 agreed to participate; 15
      subjects completed the study (7 males; baseline age 11.8 +/- 4.0 years; T1D
      duration 2.7 +/- 2.7 years; mean A1C 8.2 +/- 0.8%). Six of 8 simultaneous group
      subjects used CGM > 60% of the time for 4 months compared to 1 of 7 delayed group
      subjects (P = .02). Using SOCRATES, we could assign 87-100% of subjects to a
      single motivation stage at baseline and 4 months. This pilot study demonstrates
      the feasibility of randomizing pump naive children and adolescents with
      established T1D to simultaneous pump and CGM initiation versus standard pump
      therapy with delayed CGM initiation. Lessons from this pilot study were used to
      inform development of a full-scale multicenter RCT. 

PMID- 24876617
TI  - A model of glucose-insulin-pramlintide pharmacokinetics and pharmacodynamics in
      type I diabetes.
AB  - Type 1 diabetes mellitus (T1DM) complications are significantly reduced when
      normoglycemic levels are maintained via intensive therapy. The artificial
      pancreas is designed for intensive glycemic control; however, large postprandial
      excursions after a meal result in poor glucose regulation. Pramlintide, a
      synthetic analog of the hormone amylin, reduces the severity of postprandial
      excursions by reducing appetite, suppressing glucagon release, and slowing the
      rate of gastric emptying. The goal of this study is to create a glucose-insulin
      pramlintide physiological model that can be employed into a controller to improve
      current control approaches used in the artificial pancreas. A model of
      subcutaneous (SC) pramlintide pharmacokinetics (PK) was developed by revising an
      intravenous (IV) pramlintide PK model and adapting SC insulin PK from a glucose
      insulin model. Gray-box modeling and least squares optimization were used to
      obtain parameter estimates. Pharmacodynamics (PD) were obtained by choosing
      parameters most applicable to pramlintide mechanisms and then testing using a
      proportional PD effect using least squares optimization. The model was fit and
      validated using 27 data sets, which included placebo, PK, and PD data. SC
      pramlintide PK root mean square error values range from 1.98 to 10.66 pmol/L.
      Pramlintide PD RMSE values range from 10.48 to 42.76 mg/dL. A new in silico model
      of the glucose-insulin-pramlintide regulatory system is presented. This model can
      be used as a platform to optimize dosing of both pramlintide and insulin as a
      combined therapy for glycemic regulation, and in the development of an artificial
      pancreas as the kernel for a model-based controller. 

PMID- 24876618
TI  - Continuous glucose monitoring in newborn infants: how do errors in calibration
      measurements affect detected hypoglycemia?
AB  - Neonatal hypoglycemia is common and can cause serious brain injury. Continuous
      glucose monitoring (CGM) could improve hypoglycemia detection, while reducing
      blood glucose (BG) measurements. Calibration algorithms use BG measurements to
      convert sensor signals into CGM data. Thus, inaccuracies in calibration BG
      measurements directly affect CGM values and any metrics calculated from them. The
      aim was to quantify the effect of timing delays and calibration BG measurement
      errors on hypoglycemia metrics in newborn infants. Data from 155 babies were
      used. Two timing and 3 BG meter error models (Abbott Optium Xceed, Roche Accu
      Chek Inform II, Nova Statstrip) were created using empirical data. Monte-Carlo
      methods were employed, and each simulation was run 1000 times. Each set of
      patient data in each simulation had randomly selected timing and/or measurement
      error added to BG measurements before CGM data were calibrated. The number of
      hypoglycemic events, duration of hypoglycemia, and hypoglycemic index were then
      calculated using the CGM data and compared to baseline values. Timing error alone
      had little effect on hypoglycemia metrics, but measurement error caused
      substantial variation. Abbott results underreported the number of hypoglycemic
      events by up to 8 and Roche overreported by up to 4 where the original number
      reported was 2. Nova results were closest to baseline. Similar trends were
      observed in the other hypoglycemia metrics. Errors in blood glucose concentration
      measurements used for calibration of CGM devices can have a clinically important
      impact on detection of hypoglycemia. If CGM devices are going to be used for
      assessing hypoglycemia it is important to understand of the impact of these
      errors on CGM data. 

PMID- 24876619
TI  - A single-blind, placebo-controlled, dose-ranging trial of oral hepatic-directed
      vesicle insulin add-on to oral antidiabetic treatment in patients with type 2
      diabetes mellitus.
AB  - The dose response of postprandial plasma glucose (PPG) to add-on, premeal oral
      hepatic-directed vesicle-insulin (HDV-I), an investigational lipid bio
      nanoparticle hepatocyte-targeted insulin delivery system, was evaluated in a 3
      test-meal/day model in type 2 diabetes patients. The single-blind, placebo
      controlled, dose-escalating trial enrolled 6 patients with HbA(1c) 8.6 +/- 2.0%
      (70.0 +/- 21.9 mmol/mol) and on stable metformin therapy. Patients received oral
      HDV-I capsules daily 30 minutes before breakfast, lunch, and dinner as follows:
      placebo capsules, 0.05, 0.1, 0.2, and 0.4 U/kg on days 1, 2, 3, 4, and 5,
      respectively. Outcome measures were PPG and incremental PPG area under the
      concentration-time curve (AUC). All 4 doses of oral HDV-I statistically
      significantly lowered mean PPG (P <= .0110 each) and incremental PPG (P <= .0352
      each) AUC compared to placebo. A linear dose response was not observed. The 0.05
      U/kg dose was the minimum effective dose in the dosage range studied. Three
      adverse events unrelated to treatment were observed. Add-on oral HDV-I 0.05-0.4
      U/kg significantly lowered PPG excursions and the dose response curve was flat.
      These results are consistent with the lack of a linear dose response between
      portal and systemic plasma insulin concentrations in previous animal and human
      studies. Oral HDV-I was safe and well tolerated.

PMID- 24876620
TI  - Statistical transformation and the interpretation of inpatient glucose control
      data from the intensive care unit.
AB  - Glucose control can be problematic in critically ill patients. We evaluated the
      impact of statistical transformation on interpretation of intensive care unit
      inpatient glucose control data. Point-of-care blood glucose (POC-BG) data derived
      from patients in the intensive care unit for 2011 was obtained. Box-Cox
      transformation of POC-BG measurements was performed, and distribution of data was
      determined before and after transformation. Different data subsets were used to
      establish statistical upper and lower control limits. Exponentially weighted
      moving average (EWMA) control charts constructed from April, October, and
      November data determined whether out-of-control events could be identified
      differently in transformed versus nontransformed data. A total of 8679 POC-BG
      values were analyzed. POC-BG distributions in nontransformed data were skewed but
      approached normality after transformation. EWMA control charts revealed
      differences in projected detection of out-of-control events. In April, an out-of
      control process resulting in the lower control limit being exceeded was
      identified at sample 116 in nontransformed data but not in transformed data.
      October transformed data detected an out-of-control process exceeding the upper
      control limit at sample 27 that was not detected in nontransformed data.
      Nontransformed November results remained in control, but transformation
      identified an out-of-control event less than 10 samples into the observation
      period. Using statistical methods to assess population-based glucose control in
      the intensive care unit could alter conclusions about the effectiveness of care
      processes for managing hyperglycemia. Further study is required to determine
      whether transformed versus nontransformed data change clinical decisions about
      the interpretation of care or intervention results. 

PMID- 24876621
TI  - Can glucose be monitored accurately at the site of subcutaneous insulin delivery?
AB  - Because insulin promotes glucose uptake into adipocytes, it has been assumed that
      during measurement of glucose at the site of insulin delivery, the local glucose
      level would be much lower than systemic glucose. However, recent investigations
      challenge this notion. What explanations could account for a reduced local effect
      of insulin in the subcutaneous space? One explanation is that, in humans, the
      effect of insulin on adipocytes appears to be small. Another is that insulin
      monomers and dimers (from hexamer disassociation) might be absorbed into the
      circulation before they can increase glucose uptake locally. In addition,
      negative cooperativity of insulin action (a lower than expected effect of very
      high insulin concentrations)may play a contributing role. Other factors to be
      considered include dilution of interstitial fluid by the insulin vehicle and the
      possibility that some of the local decline in glucose might be due to the
      systemic effect of insulin. With regard to future research, redundant sensing
      units might be able to quantify the effects of proximity, leading to a
      compensatory algorithm. In summary, when measured at the site of insulin
      delivery, the decline in subcutaneous glucose level appears to be minimal, though
      the literature base is not large. Findings thus far support (1) the development
      of integrated devices that monitor glucose and deliver insulin and (2) the use of
      such devices to investigate the relationship between subcutaneous delivery of
      insulin and its local effects on glucose. A reduction in the number of
      percutaneous devices needed to manage diabetes would be welcome. 

PMID- 24876622
TI  - Intraportal islet oxygenation.
AB  - Islet transplantation (IT) is a promising therapy for the treatment of diabetes.
      The large number of islets required to achieve insulin independence limit its
      cost-effectiveness and the number of patients who can be treated. It is believed
      that >50% of islets are lost in the immediate post-IT period. Poor oxygenation in
      the early post-IT period is recognized as a possible reason for islet loss and
      dysfunction but has not been extensively studied. Several key variables affect
      oxygenation in this setting, including (1) local oxygen partial pressure (pO(2)),
      (2) islet oxygen consumption, (3) islet size (diameter, D), and (4) presence or
      absence of thrombosis on the islet surface. We discuss implications of oxygen
      limiting conditions on intraportal islet viability and function. Of the 4 key
      variables, the islet size appears to be the most important determinant of the
      anoxic and nonfunctional islet volume fractions. Similarly, the effect of
      thrombus formation on the islet surface may be substantial. At the University of
      Minnesota, average size distribution data from clinical alloislet preparations (n
      = 10) indicate that >150-um D islets account for only ~30% of the total islet
      number, but >85% of the total islet volume. This suggests that improved oxygen
      supply to the islets may have a profound impact on islet survivability and
      function since most of the beta-cell volume is within large islets which are most
      susceptible to oxygen-limiting conditions. The assumption that the liver is a
      suitable islet transplant site from the standpoint of oxygenation should be
      reconsidered.

PMID- 24876623
TI  - Percutaneous coronary intervention in patients with diabetes: current concepts
      and future directions.
AB  - Patients with diabetes and coronary artery disease represent a challenging and
      growing subset of the population. Although surgical revascularization is the
      preferred treatment for patients with diabetes and multivessel coronary artery
      disease with stable angina, a significant proportion of diabetic patients undergo
      percutaneous revascularization due to comorbidities, presence of single-vessel
      disease, or presentation with myocardial infarction. The development of drug
      eluting stents has significantly improved the results of percutaneous
      revascularization among diabetic patients, but a number of challenges remain,
      including higher rates of restenosis and stent thrombosis among diabetic
      patients. With current technologies, the outcomes of diabetic patients treated
      with noninsulin agents have approached that of nondiabetic patients. In
      comparison, patients with diabetes who require insulin therapy represent a high
      risk cohort with increased rates of target vessel failure after coronary
      revascularization. The development of bioresorbable stents and new drug elution
      systems may provide additional future benefit among patients with diabetes
      undergoing percutaneous coronary artery revascularization. 

PMID- 24876624
TI  - Vagus nerve stimulation and food intake: effect of body mass index.
AB  - Animal research suggests that vagus nerve stimulation (VNS) is associated with
      weight loss and decreased appetite. Results from human studies are mixed; some
      suggest that VNS affects weight whereas others do not, and it is unclear how VNS
      affects eating behaviors. Baseline body mass index (BMI) and VNS device settings
      may moderate the effects of VNS on caloric intake. This study investigates the
      association among BMI, VNS device settings, and caloric intake of highly
      palatable foods during VNS on versus VNS off sessions in 16 adult patients (62.5%
      female; BMI mean = 29.11 +/- 6.65) using VNS therapy for either epilepsy or
      depression. Participants attended 2 experimental sessions (VNS on versus off)
      where they were presented with 4 preferred snack foods totaling 1600 calories. At
      the start of the session, they either had their VNS devices turned off or left
      on. Caloric intake was calculated by weighing foods before and after each
      session. BMI category (overweight/obese and lean) was the between group factor in
      the analysis. After controlling for covariates, an interaction of condition and
      BMI category (P = .03) was found. There was an interaction of condition and
      device output current (P = .05) and a trend toward an interaction of condition
      and device on time (P = .07). Excess weight may impact how neurobiological
      signals from the vagus nerve affect appetite and eating. Future research is
      needed to further elucidate this relationship. 

PMID- 24876626
TI  - Self-monitoring of blood glucose: a prerequisite for diabetes management in
      outcome trials.
AB  - Evidence for the value of self-monitoring of blood glucose (SMBG) with regard to
      the achievement of treatment targets, detection of postprandial glucose
      excursions, and minimization of glycemic variability is increasing. In large
      clinical trials, SMBG is a key component for the optimization of diabetes
      treatment in insulin-treated diabetes. It also plays an essential role in outcome
      studies. However, details of SMBG use in both the methods and results sections of
      clinical articles are frequently scarce. Also, a discussion of the SMBG data and
      its impact on insulin therapy is valuable. In the recently completed Outcome
      Reduction with an Initial Glargine INtervention (ORIGIN) trial, SMBG was
      described in detail and insulin titration was largely driven by SMBG. Both
      aspects largely contributed to the fact that near-normal control was achieved
      over a long-term period. 

PMID- 24876625
TI  - The technology boom: a new era in obesity management.
AB  - As technology continues to develop rapidly, the incidence of obesity also
      continues to climb at an alarming rate. The increase in available technology is
      thought to be a contributor in the obesogenic environment, yet at the same time
      technology can also be used to intervene and improve health and health behaviors.
      This article reviews the components of effective weight management programs and
      the novel role that technology, such as SMS, websites, and smartphone apps, is
      playing to improve the success of such programs. Use of these modern technologies
      can now allow for individualized treatment recommendations to be delivered to
      individuals remotely, increased self-monitoring/tracking of health-related data,
      broader and more rapid dissemination of health information/recommendations, and
      increased patient-dietician/physician contact. The use of technology in weight
      management programs results in improved long-term weight management, and in most
      cases improved cost-effectiveness. Rather than blaming increased food intake and
      sedentary lifestyle on technology, rapidly developing and innovative technologies
      should be used to our advantage and deployed to combat the obesity epidemic. 

PMID- 24876627
TI  - Transitioning to a national (New Zealand) sole supply scheme for glucose meters:
      lessons learned, problems yet to be solved.
AB  - This case study describes the clinical impact of moving to a single brand of
      glucose test strips. In 2013 the New Zealand public health system completed a
      move to procure test strips at a significant discount. The associated direct
      savings is estimated at around 40% of the total glucose strip budget. Half the
      local diabetes population undertake glucose monitoring using government-funded
      diabetes supplies. These patients no longer have a choice of brand of meters and
      strips. Although the majority of patients adapted well to this change, a small
      percentage did not. Also, some consumers expressed concerns about analytical
      performance of the new strips, when used in everyday life. A pragmatic
      postmarketing surveillance system, designed with consumer input, may help address
      these residual concerns. 

PMID- 24876628
TI  - Contributions of overnight glycemia to the overall hyperglycemia of type 2
      diabetic patients: variations with HbA1c levels.

PMID- 24876629
TI  - Vibration perception threshold in the screening of sensorimotor distal symmetric
      polyneuropathy: the need of more accurate age-specific reference values.

PMID- 24876630
TI  - Corrigendum.
AB  - We Need More Research and Better Designs for Insulin Infusion Sets. 2014;8(2);199
      202. DOI: 10.1177/1932296814523882. 

PMID- 24876631
TI  - Artemisinin induces hormonal imbalance and oxidative damage in the erythrocytes
      and uterus but not in the ovary of rats.
AB  - Artemisinin is an antimalarial drug previously reported to induce neurotoxicity
      and embryotoxicity in animal models. This study investigated the erythrocytes and
      reproductive toxicity potentials of artemisinin in female rats. Animals were
      randomly divided into four study groups of eight rats each. The control group
      (group I) received corn oil, the vehicle, while groups II-IV were orally exposed
      to 7, 35 and 70 mg kg(-1) day(-1) of artemisinin, respectively, by gastric
      intubation for 7 consecutive days. Subsequently, we evaluated the impact of
      artemisinin on the endocrine environment and selected markers of oxidative damage
      and antioxidant status of the erythrocytes, ovary and uterus. Artemisinin
      significantly increased hydrogen peroxide (H2O2) and malondialdehyde (MDA) levels
      and decreased catalase, glutathione peroxidase and superoxide dismutase
      activities in erythrocytes and uterus of rats compared with control group (p <
      0.05). However, artemisinin did not alter ovarian MDA, H2O2, glutathione levels
      and catalase activity, while ovarian and uterine histological assessment revealed
      absence of visible lesions. Moreover, artemisinin significantly decreased
      follicle-stimulating hormone and increased progesterone levels compared with
      control (p < 0.05). Thus, these data suggest that in the absence of malarial
      parasite infection, artemisinin induced hormonal imbalance and oxidative damage
      in the erythrocytes and uterus but spared the ovary of rats. 

PMID- 24876633
TI  - Psychometric Properties of the Psychopathy Checklist: Youth Version Among
      Portuguese Juvenile Delinquents.
AB  - The main aim of the present study was to examine some psychometric properties of
      the Psychopathy Checklist: Youth Version (PCL:YV) among Portuguese juvenile
      delinquents. With forensic sample of 192 incarcerated male participants, the
      Portuguese version of the PCL:YV demonstrated promising psychometric properties
      of the three-factor model of youth psychopathy, internal consistency, convergent
      validity, concurrent validity, and retrospective validity that generally justify
      its use among Portuguese youths. Statistically significant associations were
      found with age of criminal onset, frequency of crimes, number of victims, and use
      of physical violence. 

PMID- 24876632
TI  - Grounding evidence-based approaches to cancer prevention in the community: a case
      study of mammography barriers in underserved African American women.
AB  - When community health planners select an evidence-based intervention that has
      been developed and tested in one situation and adapt it for use in a different
      situation or community, best practice suggests needs assessment and formative
      research in the new setting. Cancer prevention planners who are interested in
      adopting and adapting evidence-based approaches need to base their choices on a
      sound understanding of the health or behavioral risk problem in which they mean
      to intervene. This requires a balancing act of weighing community information
      against a broader perspective from the scientific literature and using the
      combination to identify and adapt an evidence-based intervention program that is
      likely to be effective in the new setting. This report is a case study of a
      community and organizational assessment conducted as a foundation for selecting
      and recommending adaptation of an evidence-based intervention for improving
      mammography appointment attendance. We used an inductive sequential exploratory
      mixed-methods design to inform this process. The process provides a model for
      formative research grounding evidence-based practice for cancer control planners.
      Future studies that incorporate findings from needs assessment into the
      adaptation of the selected intervention program may promote the effective
      dissemination of evidence-based programs. 

PMID- 24876634
TI  - Strain Localization in an Oscillating Maxwell Viscoelastic Cylinder.
AB  - The transient rotation responses of simple, axisymmetric, viscoelastic structures
      are of interest for interpretation of experiments designed to characterize
      materials and closed structures such as the brain using magnetic resonance
      techniques. Here, we studied the response of a Maxwell viscoelastic cylinder to
      small, sinusoidal displacement of its outer boundary. The transient strain field
      can be calculated in closed form using any of several conventional approaches.
      The solution is surprising: the strain field develops a singularity that appears
      when the wavefront leaves the center of the cylinder, and persists as the
      wavefront reflects to the outer boundary and back to the center of the cylinder.
      The singularity is alternately annihilated and reinitiated upon subsequent
      departures of the wavefront from the center of the cylinder until it disappears
      in the limit of steady state oscillations. We present the solution for this
      strain field, characterize the nature of this singularity, and discuss its
      potential role in the mechanical response and evolved morphology of the brain.

PMID- 24876636
TI  - Effect of packaging materials and storage environment on postharvest quality of
      papaya fruit.
AB  - This experiment was conducted to assess the effects of packaging materials and
      storage environments on shelf life of papaya fruit (Carica papaya L.). A
      factorial combination of five packaging materials and two storage environments
      using randomized complete block design with three replications were used. The
      papaya fruits were evaluated for weight loss, percentage marketability, firmness,
      total soluble solids, pH, titratable acidity, ascorbic acid, reducing sugar and
      total sugar content. The packaged and cooled fruits remained firmer than
      unpackaged and evaporatively cooled fruits. Higher chemical compositions were
      recorded in the control fruits stored under ambient conditions during the earlier
      times of storage. Packaging and cooling maintained the chemical quality of papaya
      fruits better than the control sample fruits towards the end of storage periods.
      The evaporatively cooled storage combined with packaging improved the shelf life
      of papaya fruits by more than two fold. The polyethylene bag packaging combined
      with evaporatively cooled storage maintained the superior quality of papaya fruit
      for a period of 21 days. This integrated agro-technology is recommended for
      postharvest loss reduction biotechnology in hot regions. 

PMID- 24876635
TI  - Health benefits of finger millet (Eleusine coracana L.) polyphenols and dietary
      fiber: a review.
AB  - The growing public awareness of nutrition and health care research substantiates
      the potential of phytochemicals such as polyphenols and dietary fiber on their
      health beneficial properties. Hence, there is in need to identify newer sources
      of neutraceuticals and other natural and nutritional materials with the desirable
      functional characteristics. Finger millet (Eleusine coracana), one of the minor
      cereals, is known for several health benefits and some of the health benefits are
      attributed to its polyphenol and dietary fiber contents. It is an important
      staple food in India for people of low income groups. Nutritionally, its
      importance is well recognised because of its high content of calcium (0.38%),
      dietary fiber (18%) and phenolic compounds (0.3-3%). They are also recognized for
      their health beneficial effects, such as anti-diabetic, anti-tumerogenic,
      atherosclerogenic effects, antioxidant and antimicrobial properties. This review
      deals with the nature of polyphenols and dietary fiber of finger millet and their
      role with respect to the health benefits associated with millet. 

PMID- 24876637
TI  - Microwave-assisted hydrodistillation of essential oil from rosemary.
AB  - Effects of microwave assisted hydrodistillation (MAHD) and conventional
      hydrodistillation (HD) methods on yield, composition, specific gravity,
      refractive index, and antioxidant and antimicrobial activities of essential oil
      of Rosmarinus officinalis L were studied. The main aroma compounds of rosemary
      essential oil were found as 1,8-cineole and camphor. Trolox equivalent
      antioxidant capacity (TEAC) values for essential oils extracted by MAHD and HD
      were 1.52 mM/ml oil and 1.95 mM/ml oil, respectively. DPPH radical scavenging
      activity of the oils obtained by MAHD and HD were found as 60.55% and 51.04%
      respectively. Inhibitory effects of essential oils obtained by two methods on
      linoleic acid peroxidation were almost the same. Essential oils obtained by two
      methods inhibited growth of Esherichia coli O157:H7, Salmonella typhimurium NRRLE
      4463 and Listeria monocytogenes Scott A with the same degree. However, inhibitory
      activity of essential oil obtained by MAHD on Staphylococcus aureus 6538P was
      stronger than that of obtained by HD (p < 0.05). 

PMID- 24876638
TI  - Effect of pentosans addition on pasting properties of flours of eight hard white
      spring wheat cultivars.
AB  - The effects of water extractable pentosans (WEP) and water unextractable
      pentosans (WUP) on pasting properties in flours of eight different hard white
      spring wheat (HWSW) cultivars was studied. WEP and WUP isolated from a hard wheat
      flour were added to each of the cultivars at 1% and 2% level. The results
      indicated that WEP exhibited a pronounced effect on pasting properties as
      compared to WUP and variety. Univariate analysis of variance (ANOVA) was used to
      evaluate sources of variation. The variety significantly (P < 0.001) influenced
      all the pasting parameters. WUP caused significant (P < 0.001) variation in paste
      viscosities (except breakdown). WEP influenced more pronouncedly the hot paste,
      cold paste, breakdown and setback viscosities with F values-221.802, 214.286,
      98.073 and 120.159, respectively. Variety-by-WEP interaction exhibited
      significant (P < 0.01) influence on pasting time, peak, hot paste and cold paste
      viscosities. Whereas, variety-by-WUP interaction only significantly (P < 0.001)
      influenced the pasting- time and -temperature. Duncan's test was used to analyze
      the significant difference (P < 0.05) within the variety. The results revealed
      that WUP did not induce significant (P < 0.05) influence on all the pasting
      parameters, whereas, WEP influenced significantly (P < 0.05) the paste
      viscosities of some of the varieties. It was also found that the addition of WEP
      remarkably reduced the setback, hot paste, cold paste viscosities and increased
      the breakdown viscosity in all cultivar flours. The effect of WEP was greater at
      higher level of supplementation on paste viscosities. 

PMID- 24876639
TI  - Effect of frying conditions on the physico-chemical properties of rice bran oil
      and its blended oil.
AB  - The changes occurring in rice bran oil and its blend with sunflower oil during
      repeated frying cycles of dried and moist potato chips were monitored. The
      parameters assessed were: Colour, Refractive Index, SpecificGravity, Oryzanol
      Value, Free fatty acid, Iodine Value, Peroxide value, anisidine value,
      Saponification Value, trans fats and fatty acid composition. No significant
      changes (p<=0.05) were observed in the refractive index and specific gravity of
      rice bran oil, sunflower oil and their model blend. The colour of blended oil was
      lesser than RBO and the intensity of color increased after each frying cycle
      during the deep fat frying of moistened and dried potato chips. The oryzanol
      content and iodine value decreased with the frying cycles. The decrease in
      oryzanol value during the frying operation was more prominent in rice bran oil as
      compared to the blended oils. The increase in p-anisidine value was more in rice
      bran oil as compared to blended oil. No significant changes (P<0.05) in the
      myristic, palmitic and stearic acid composition was observed during the repeated
      deep fat frying cycles in both the rice bran oil and blended oils samples. The
      amount of unsaturated fatty acid decreased gradually during repeated deep fat
      frying cycles in both the oils. The trans fat increased with repeated deep fat
      frying cycles in both the rice bran and blended oils, when used to fry moistened
      and dried potato chips. Both the oil samples showed greater formation of trans
      fatty acids when the moistened potato chips were used during frying. 

PMID- 24876640
TI  - Effect of emulsifiers on oil separation problem and quality characteristics of
      Tahin Helva during storage.
AB  - Tahin helva is one of Turkish traditional confectionary foods. Sesame paste,
      sugar syrup and soapwort extract were used for tahin helva's production. The
      purpose of this study was to solve the oil separation problem occurred in tahin
      helva by using food additives permitted as an emulsifier for tahin helva in the
      Turkish and EU Codex. Sorbitan tristearate (STS), sorbitan monopalmitate (SMP)
      and their combinations (STS:SMP, 1:1) were added to tahin helva, then helva
      samples were stored at the storage temperatures of 20  degrees C, 30  degrees C,
      and 40  degrees C. The emulsifiers did not have any effect on physical, chemical
      and sensory properties of tahin helva except on its oil content, whereas storage
      temperature and storage time had effects on those properties of helva. STS:SMP
      combination was found to be statistically more effective than SMP and STS
      formulations in preventing oil separation. Penetration force of tahin helva has
      increased by increasing the storage temperature and storage time. It was found
      that there was a decrease in -a colour value of helva through the storage time at
      20  degrees C and 30  degrees C, while there was an increase in that value at 40 
      degrees C. The highest change in the moisture content of all helva samples
      through storage was observed at the storage temperature of 20  degrees C. Sensory
      scores for appearance, texture and flavour characteristics of helva have
      decreased significantly during the storage period. 

PMID- 24876641
TI  - Identification of phenolic compositions and the antioxidant capacity of mandarin
      juices and wines.
AB  - This research was undertaken to determine the phenolic composition and
      antioxidant capacity of juices and wines obtained from Robinson, Fremont and
      Satsuma mandarins. High-performance liquid chromatography coupled with diode
      array detection was used for identifying and quantifying phenolic compounds. The
      total amount of phenolic compounds ranged from 36.6 to 132.6 mg/L for the
      mandarin juice, and from 14.1 to 54.5 mg/L for the wines. In the juices and
      wines, the major hydroxybenzoic acid was vanillic acid; the major hydroxycinnamic
      acid was ferulic acid; and the major flavanone was hesperidin. The antioxidant
      activity was measured using the DPPH and ABTS radical scavenging assays, and the
      antioxidant capacity of mandarin juices was found to be higher than that of
      wines. Results of this study indicated that these mandarin wines had a
      composition similar to other beverages, thus demonstrating that these fruits have
      the potential to be used to produce fermented beverages. 

PMID- 24876642
TI  - Modification of fish skin collagen film and absorption property of tannic acid.
AB  - Fish collagen is a biomacromolecule material and is usually used as a clarifying
      agent. However, fish collagen is not recyclable, and sedimentation usually occurs
      in the clarification process using fish collagen so that the filtration process
      is inevitable. This work aimed to provide a recyclable modified fish skin
      collagen film (MFCF) for adsorption of tannic acids. The collagen from channel
      catfish skin was extracted and used for preparation of the fish skin collagen
      film (FCF) and MFCF. The result indicated that the mechanical properties of MFCF
      were improved by addition of 2 ml/L glycerol, 6 ml/L polyvinyl alcohol (PVA) and
      2 ml/L glutaraldehyde in 15 g/L collagen solution. As the most important property
      of adsorption material, the hydroscopicity of MFCF was only 54%, significantly
      lower than that of FCF (295%). Therefore, MFCF would not collapse in water. The
      infrared and thermal properties of MFCF were also investigated in this work.
      Results indicated that, in comparison to FCF, the physical and chemical
      properties of MFCF had been improved significantly. MFCF had higher shrink
      temperature (79.3  degrees C) and it did not collapse in distilled water at
      normal temperature. Furthermore, absorption and desorption properties of tannic
      acid were studied. MFCF showed good capability of absorption and desorption of
      tannic acid, which leaded to the suggestion that MFCF could have potential
      applications in adsorption material. 

PMID- 24876643
TI  - Development and shelf-life evaluation of pearl millet based upma dry mix.
AB  - Upma, a popular breakfast of southern India, traditionally made from wheat, was
      prepared using pearl millet semolina (PMS). Prior to preparation of semolina,
      pearl millet grains were hydro-thermally treated to reduce anti-nutritional
      factors and inactivate lipase activity. Hydrothermal treatments (soaking up to
      moisture 30 +/- 2%, steaming 1.05 kg cm(-2), 20 min) reduced the anti-nutritional
      factors significantly (p <= 0.05). No lipase activity was detected after
      steaming. Central composite rotatable design (CCRD) with three independent
      variables i.e. vanaspati (vegetable fat), citric acid and water for rehydration
      were used to design the experiments. Sensory responses and rehydration ratio were
      used to study the individual and interactive effects of variables. Sensory score
      for taste varied from 6.5 to 8.1, mouth feel 6.7-8.0, overall acceptability 6.7
      8.1 and rehydration ratio from 2.4 to 3.3. Based upon the experiments, the
      optimized level of ingredients was: vanaspati 46.5 g 100 g(-1) PMS, citric acid
      0.17 g 100 g(-1) PMS and water for rehydration 244.6 ml 100 g(-1) dry mix with
      98.5% desirability. The prepared upma mix was monitored for peroxide value, free
      fatty acids and thiobarbituric acid value as well as sensory quality during
      storage and was found stable for 6 months at ambient conditions (20-35  degrees
      C) in poly ethylene pouches (75 MU). 

PMID- 24876644
TI  - Biogenic amines, amino acids and microflora changes in Indian mackerel
      (Rastrellinger kanagurta) stored at ambient (25-29  degrees C) and ice
      temperature (0  degrees C).
AB  - Biogenic amines formation in Indian mackerel of tropical region was investigated
      during storage at ambient (25-29  degrees C) and ice temperature (0  degrees C)
      in relation with changes of amino acids content and amines forming bacteria. All
      amines increased significantly during storage at two temperatures except for
      spermidine and spermine. Histamine concentration of 363.5 ppm was detected after
      16 h stored at ambient temperature. Aerobic plate count of fish stored at ambient
      temperature reached 6.98 log CFU g(-1) after 16 h, close to the upper limit (7
      log CFU g(-1)) suggested by International Commission on the Microbiological
      Specifications for Foods (ICMSF). However, proper icing procedure retarded the
      formation of histamine effectively, resulting only 8.31 ppm after 16 days of ice
      storage. Aerobic plate count of 5.99 and 7.72 log CFU g(-1) were recorded for
      fish stored in ice after 16 days and ambient temperature after 20 h,
      respectively. Histamine exhibited high correlation with histidine (r(2) = -0.963,
      P < 0.01) as well as cadaverine with lysine (r(2) = -0.750, P < 0.05). However,
      tyramine-tyrosine demonstrated a weaker relationship (r(2) = -0.138, P > 0.05).
      As storage time progressed, the amines forming bacteria grew significantly except
      for that stored in ice. 

PMID- 24876645
TI  - Comparative evaluation of Jatropha curcas L. seed meals obtained by different
      methods of defatting on toxic, antinutritional and nutritive factors.
AB  - Different methods of defatting have a great impact on toxic, antinutritional and
      nutritive factors in the oilseed meals. In order to find the most suitable
      methods of defatting for Jatropha curcas seed meals, the Jatropha curcas L. seed
      meals, defatted by Soxhlet extraction and screw-press were characterized for
      their toxic, anti-nutritional and nutrient factors in this study. The toxins
      (phorbolesters, 3.1 and 2.9 mg/g) and some anti-nutritional factors (saponins,
      2.9 and 2.6%; phytates, 11.1 and 11.6%) in meals obtained by the two defatting
      methods were present at high concentrations. However, the trypsin inhibitors
      activity (TIA) and lectin (2.7 mg/g and 1.5 mg/ml) in the screw-pressed meal were
      significantly lower, due to the high temperature (120  degrees C) used in this
      defatting process. From nutritional side, the values of crude protein (CP),
      buffer-soluble nitrogen, non-protein nitrogen, pepsin insoluble nitrogen, in
      vitro protein digestibility (IVPD), as well as essential amino acid index (EAAI),
      biological value (BV), nutritional index (NI) and protein-digestibility-corrected
      amino acid score (PDCAAS) of the meal obtained by Soxhlet extraction were better
      than the screw-pressed meal. However, taking practical application into account,
      from detoxification side, screw-pressed meal is better for detoxification. 

PMID- 24876646
TI  - Migration study of optical brighteners from polymer packing materials to jam
      squeeze and fruit drink by spectrofluorimetry and RP-HPLC methods.
AB  - Optical brighteners are commonly used to modify the appearance and to improve
      polymer properties of packaging. They are not chemically bound to polymers and
      able to migrate from packaging into the foods. These migrants are potentially
      harmful to human health. In concern with human safety an approach was made to
      analyze three optical brighteners such as diphenylbutadiene, Uvitex-OB,
      benzophenone in commercial fruit juice and jam. The migration level of these
      optical brighteners from low density poly ethylene packaging into fruit juice and
      jam was studied. Two optimized and validated analytical techniques such as
      spectrofluorimetry and high performance liquid chromatography with photo diode
      array detector used for migration study. Both methods have shown high correlation
      coefficients (>0.999), over a concentration range of 0.1-3.2 MUg/mL, 0.1-1
      MUg/mL, 0.05-3.2 MUg/mL for diphenylbutadiene, Uvitex-OB and benzophenone
      respectively. The preliminary studies confirm that the low density poly ethylene
      layer taken for study contained of diphenylbutadiene and the other two were
      absent. The migration level of diphenylbutadiene was studied at room temperature
      and different elevated temperature from 30  degrees C to 60  degrees C for up to
      3 weeks. At room temperature no migration of diphenylbutadiene was observed where
      as at higher temperature migration could be observed. The maximum quantity of
      diphenylbutadiene migrated was found to be 0.0462 mg/kg from tetrapak, and 0.0382
      mg/kg from jam squeeze after 3 weeks treatment at 60  degrees C. The migration of
      diphenylbutadiene was found to be less than allowable concentration during the
      study period. 

PMID- 24876647
TI  - Development and quality evaluation of value added instant rab mixes.
AB  - Rab is a traditional Rajasthani preparation prepared by boiling maize grits and
      or flour in buttermilk for 2-3 h. It is sour in taste with curd and cumin seed
      flavour and has thick soup like consistency. Two instant mixes of rab were
      developed using two types of curds prepared from two different culture
      combination (i) S. lactis + S. thermophilus + S. diacetylactis and (ii) L.
      bulgaricus + S. diacetylactis. Processed greengram dhal and spinach leaves powder
      were added to the mixes for their value addition. In all, six mixes were
      developed from two types of curd. The mixes were analysed for nutritional
      composition at zero month and sensory characteristics and shelf life was
      evaluated for 4 months. The rab mixes provided moisture 4.0-5.5 g; protein 15.1
      17.6 g; carbohydrate 62.3-70.29 g; energy 357-394 kcal; fat 4.4-6.1 g; iron 3.15
      3.89 mg and calcium 346-386 mg per 100 g of mixes. There was an increase in
      protein, ash, fiber and iron content of mixes through value addition. Sensory
      evaluation of rab reconstituted from mixes revealed that the scores ranged
      between 7 and 8 depicting that rab was liked very much. The mixes were free from
      coliforms and S.aureus bacteria and the counts for TVC, yeast and molds were
      within safe limits during storage of 4 months at 28-30 degrees C and RH 55-65%. 

PMID- 24876649
TI  - Studies on the optimization and stability of instant wheat porridge (Dalia) mix.
AB  - Instant wheat porridge (Dalia) mix based on precooked broken wheat, sugar, skim
      milk powder and flavouring agents was developed using response surface
      methodology and central composite rotatable design. Stability of instant wheat
      porridge (Dalia) mix packed in polypropylene (PP) and metallised polyester (MP)
      pouches was evaluated. Instant porridge (Dalia) mix remained stable for 9 and 12
      m respectively in PP and MP pouches under ambient temperature (15-34  degrees C)
      conditions. Deterioration in instant porridge mix during storage was mainly
      caused by autoxidation of lipids, browning due to maillard reaction and
      development of off-flavour. 

PMID- 24876648
TI  - Dahi containing Lactobacillus acidophilus and Bifidobacterium bifidum improves
      phagocytic potential of macrophages in aged mice.
AB  - The present study investigated the effect of Dahi containing potential probiotic
      bacterial strains on macrophage functions in ageing mice. Probiotic Dahi was
      prepared by co-culturing Dahi bacteria (Lactococcus lactis ssp. cremoris and
      Lactococcus lactis ssp. lactis biovar diacetylactis) along with Lactobacillus
      acidophilus LaVK2 (La-Dahi) or combined L. acidophilus LaVK2 and Bifidobacterium
      bifidum BbVK3 (LaBb-Dahi) in buffalo milk. The effect of ageing on phagocytic
      function was evaluated on 4 mo, 12 mo and 16 mo old mice. The effect of probiotic
      Dahi was evaluated for macrophage functions in ageing mice (12 mo old) fed La
      Dahi or LaBb-Dahi supplements for 4 months. The production of extracellular
      superoxide and H2O2 declined in peritoneal macrophages but enhanced in splenic
      macrophages, while intracellular superoxide declined in both peritoneal and
      splenic macrophages with ageing in mice. A decline in phagocytic activity of
      peritoneal macrophages was also observed in aged mice. Supplementation of diet
      with La-Dahi or LaBb-Dahi for 4 months improved production of reactive oxygen
      species and phagocytic and adherence indices of peritoneal macrophages in aged
      mice. These results suggest that oral administration of La-Dahi or LaBb-Dahi has
      potential to improve immune functions in ageing individuals. 

PMID- 24876650
TI  - Microbial based assay for specific detection of beta-lactam group of antibiotics
      in milk.
AB  - The spore forming Bacillus cereus (66) was screened for the induction of beta
      lactamase in presence of an inducer using iodometric assay. A significant
      induction in marker enzyme was observed in B. cereus 66 at maximum residual limit
      (MRL) of penicillin, ampicillin, cloxacillin, amoxicillin, cefalexin, and
      cephazolin belonging to beta-lactam group of antibiotics. A microbial based
      assay, where enzyme induction was optimized at pH 7.0, temperature 30 degrees C,
      and whey powder (0.25%) after 4 h of incubation. The spore based assay was tested
      with milk samples spiked with 6 different beta-lactam antibiotics. The results
      were 100 and 83.33% in correlation with microbial receptor and inhibition based
      assay, respectively. Overall, spore based assay can be a useful and cost
      effective tool for the specific detection of beta-lactam group of antibiotics in
      milk. 

PMID- 24876651
TI  - Study of antioxidant activity of non-conventional Brazilian fruits.
AB  - This study aimed to analyze the proximate composition of seeds from some non
      conventional Brazilian fruits, as well as to evaluate the antioxidant activity
      through DPPH(*) free radical and to quantify the total phenolic compounds. To
      obtain the extracts, dried and crushed seeds were extracted with ethanol for 30
      min, in a ratio of 1:3 (seeds:ethyl alcohol), under continuous agitation, at room
      temperature. Then, the mixtures were filtered and the supernatants were subjected
      to rotary evaporator under pressure reduced to 40  degrees C. The results report
      that the seeds of non-conventional fruits are remarkable sources of lipids, and
      the extraction of oil from these seeds could be an alternative for the commercial
      utilization of waste. They also presented significant percentages of protein and
      carbohydrates. Ethanol extracts of seeds from non-conventional Brazilian fruits
      showed relevant antioxidant activity and high amount of phenolic compounds.
      Therefore Brazilian non-conventional fruits can be used as functional food
      products or feed. 

PMID- 24876652
TI  - Physico-chemical and sensory changes during the storage of lal peda.
AB  - Lal peda is a popular heat desiccated traditional dairy delicacy of eastern India
      specially Uttar Pradesh. It is prepared by blending of khoa and sugar followed by
      heat desiccation until characteristic reddish brown colour appears. It is a
      nutritive, palatable and a very good source of energy. In order to commercially
      manufacture and market lal peda, studies on its shelf-life were considered to be
      very important. Lal peda samples were packed in paper boxes and stored at two
      different temperatures i.e. 4 and 37  degrees C and physico-chemical and sensory
      changes were monitored during storage period. There was a continuous loss of
      moisture during storage and rate of loss of moisture was higher at 37  degrees C.
      FFA and HMF contents in lal peda increased during storage and these changes were
      found to be temperature sensitive. Changes in textural properties of lal peda in
      terms of hardness, springiness, cohesiveness, chewiness and gumminess were also
      studied. Lal peda samples stored at 4 and 37  degrees C were acceptable up to 31
      days and 9 days, respectively on the basis of textural and sensory attributes. 

PMID- 24876653
TI  - Prediction of textural attributes using color values of banana (Musa sapientum)
      during ripening.
AB  - Banana is an important sub-tropical fruit in international trade. It undergoes
      significant textural and color transformations during ripening process, which in
      turn influence the eating quality of the fruit. In present study, color ('L', 'a'
      and 'b' value) and textural attributes of bananas (peel, fruit and pulp firmness;
      pulp toughness; stickiness) were studied simultaneously using Hunter Color Lab
      and Texture Analyser, respectively, during ripening period of 10 days at ambient
      atmosphere. There was significant effect of ripening period on all the considered
      textural characteristics and color properties of bananas except color value 'b'.
      In general, textural descriptors (peel, fruit and pulp firmness; and pulp
      toughness) decreased during ripening except stickiness, while color values viz
      'a' and 'b' increased with ripening barring 'L' value. Among various textural
      attributes, peel toughness and pulp firmness showed highest correlation (r) with
      'a' value of banana peel. In order to predict textural properties using color
      values of banana, five types of equations
      (linear/polynomial/exponential/logarithmic/power) were fitted. Among them,
      polynomial equation was found to be the best fit (highest coefficient of
      determination, R(2)) for prediction of texture using color properties for
      bananas. The pulp firmness, peel toughness and pulp toughness showed R(2) above
      0.84 with indicating its potentiality of the fitted equations for prediction of
      textural profile of bananas non-destructively using 'a' value. 

PMID- 24876654
TI  - Purification and properties of heat-stable extracellular protease from
      Pseudomonads fluorescens BJ-10.
AB  - Pseudomonas fluorescens BJ-10, a kind of psychrotrophic bacteria, was isolated
      from raw milk. It produced an extracellular protease of 47 kDa by SDS-PAGE. The
      crude proteases were purified by ammonium sulfate fractionation, ion-exchange and
      gel filtration chromatography. The specific activity of purified protease
      increased 61.38-fold. The optimum pH and temperature were pH 7.0 and 30  degrees
      C, respectively. The purified protease was partially inhibited by DL
      dithiothreitol, and the activity increased a little upon Fe(2+) addition. The
      protease showed typical heat-stable behavior. After treatment at 100  degrees C
      for 3 min, more than 94% activity remained. This work might lay the foundation
      for possible relationship between the heat stable protease and gelation of UHT
      milk. 

PMID- 24876655
TI  - Storage stability of smoked buffalo rumen meat product treated with ginger
      extract.
AB  - Smoked buffalo rumen meat products were prepared from 3 times blade tenderized
      buffalo tripe with 5.0% ginger extract and were subjected to various physico
      chemical parameters, microbial profile and sensory quality at 25 +/- 1  degrees C
      under aerobic packaging. All physico-chemical parameters, microbial counts and
      sensory evaluation score of ginger extract treated buffalo rumen meat product
      were higher compared to control. pH, moisture content, thiobarbituric acid,
      tyrosine values, total plate, yeast and mould and staphylococcal counts were
      increased and extract release volume were decreased significantly with increasing
      storage period. Throughout the storage period, all microbial counts and sensory
      evaluation score were within the acceptable limits up to storage period of 15
      days at 25 +/- 1  degrees C in LDPE pouches under aerobic packaging. 

PMID- 24876656
TI  - Detecting the specific parameters that affect the maturation of farmed sea bass
      (Dicentrarchus labrax) fillets stored in sunflower oil.
AB  - In this study, it was aimed to detect the specific parameters that effect the
      maturation of farmed sea bass fillets stored in sunflower oil. Sea bass fillets
      were taken into the pickling solution (2.5% acetic acid and 11% sodium chloride)
      at 4  degrees C(+/-1). Fish meat in each group was analysed for the following
      parameters; pH, moisture%, acetic acid% and NaCl% in the maturation pickling
      solution and in sunflower oil. At the end of the 90 days storage, there were not
      any negative situations about the fish in terms of the scientific approach. It
      was detected that the skinless samples had the less NaCl and acidity values but
      scaly and scaleless samples had the higher values. Main reasons are: for the
      scaly and scaleless samples, the skin acted as a barrier in the pickling solution
      or oil and for scaly samples, scales depart from the skin and defeat the passing
      of NaCl and acid to the meat. When evaluating this study results, the fillet
      group samples which contain more salt and acetic acid are thought to be more
      appropriate for marinating in terms of shelf-life and quality. 

PMID- 24876657
TI  - Evaluation of sensory acceptability and storage stability of frozen carrot based
      dessert.
AB  - In the present study a recipe for frozen carrot based dessert (carrot halwa) was
      standardized on the basis of sensory characteristics such as appearance, odor,
      texture, taste and overall acceptability (OAA). The product was developed without
      addition of pure ghee to improve the storage stability under frozen conditions (
      20  degrees C). Sensory properties of the developed product (OAA score = 8.60)
      were found to be equally good as compared to the conventional carrot halwa (OAA
      score = 8.75) which was prepared using pure ghee. From the physico-chemical
      analysis the developed product was found to have lower amount of fat (ca. 12%)
      than the conventional one. During the frozen storage, microbial growth in the
      product was found to be non-significant (P > 0.05). The free fatty acid content,
      peroxide value and thiobarbituric acid content increased during frozen storage of
      15 months. But the increase was insignificant. Loss in total carotenoids content
      of the product was found to be 60.5% from initial value at the end of 15 months
      frozen storage. 

PMID- 24876659
TI  - A novel method to stabilize meat colour: ligand coordinating with hemin.
AB  - Carbon monoxide (CO), L-cysteine and L-histidine were tested to coordinate with
      hemin chloride (pigment containing haem iron). In the presence of sodium
      dithionite, both CO and L-cysteine could react with hemin to afford respectively
      the corresponding complexes: CO-hemin and L-cysteine hemin; while L-histidine
      could not react with hemin. Both CO-hemin and L-cysteine hemin could decompose
      and release the corresponding ligand to generate hemin. Both light and
      temperature had an obvious effect on stabilization of these complexes. By sensory
      evaluation, both CO-hemin and L-cysteine hemin have bright red colour and show a
      potential as cured cooked-meat pigments (CCMP) in the manufacture of meat
      product. 

PMID- 24876658
TI  - Influence of Lentinus edodes and Agaricus blazei extracts on the prevention of
      oxidation and retention of tocopherols in soybean oil in an accelerated storage
      test.
AB  - This study aimed to evaluate the influence of the methanol extracts of mushrooms
      Lentinus edodes and Agaricus blazei on the retention of tocopherols in soybean
      oil, when subjected to an accelerated storage test. The following treatments were
      subjected to an accelerated storage test in an oven at 60  degrees C for 15 days:
      Control (soybean oil without antioxidants), TBHQ (soybean oil + 100 mg/kg of
      TBHQ), BHT (soybean oil + 100 mg/kg of BHT), L. edodes (soybean oil + 3,500 mg/kg
      of L. edodes extract) and A. blazei (soybean oil + 3,500 mg/kg of A. blazei
      extract). The samples were analyzed for tocopherols naturally present in soybean
      oil and mass gain. The results showed, the time required to reach a 0.5% increase
      in mass was 13 days for TBHQ and 15 days for A. blazei. The content of
      tocopherols for TBHQ was 457.50 mg/kg and the A. blazei, 477.20 mg/kg. 

PMID- 24876660
TI  - Nisin based stabilization of novel fruit and vegetable functional juices
      containing bacterial cellulose at ambient temperature.
AB  - The current study reports the preparation and stabilization of novel functional
      drinks based on fruit and vegetable juices incorporating bacterial cellulose from
      Acetobacter xylinum. Pineapple, musk melon, carrot, tomato, beet root and a blend
      juice containing 20 % each of carrot and tomato juice with 60 % beet root juice
      has been studied. These juices have been stabilized over a storage period of 90
      days at 28  degrees C, by the use of nisin and maintaining a low pH circumventing
      the need for any chemical preservatives or refrigeration. Instrumental color
      values have been correlated with the pigment concentrations present in the fresh
      as well as stored juices. There was 36, 72 and 60 % loss of total carotenoids in
      the case of carrot, pineapple and musk melon juices respectively while the
      lycopene content remained unchanged after 90 days of storage. The betanin content
      decreased 37 % in the case of beetroot juice and 25 % in the case of beetroot
      juice blended with carrot and tomato juices. Sensory analysis has revealed a
      clear preference for the beetroot blended mixed juice. 

PMID- 24876661
TI  - Improved synthesis of structural analogues of (-)-epicatechin gallate for
      modulation of staphylococcal beta-lactam resistance.
AB  - The high-yielding synthesis of enantiomerically pure epicatechin gallate
      analogues where the A and/or B-ring hydroxylation is reduced or altered has been
      achieved by optimising routes to the catechin stereochemistry. The B-ring
      analogues were synthesised by using an electrophilic ring closure onto an
      enantiomerically enriched epoxide as a key step. The A and B-ring hydroxyl
      deleted analogues were synthesised through a Mitsunobu cyclisation. For the B
      ring analogues, the anti- (catechin) stereochemistry was converted to the syn-
      (epicatechin) stereochemistry by a known oxidation/reduction protocol. Absolute
      stereochemistry was derived from either a Sharpless epoxidation or asymmetric
      dihydroxylation.

PMID- 24876662
TI  - UNITED STATES DENTAL PROFESSIONALS' PERCEPTIONS OF DENTAL ANXIETY AND NEED FOR
      SEDATION IN PATIENTS WITH MENTAL ILLNESS.
AB  - Dental fear is a barrier to receiving dental care, particularly for those
      patients who also suffer from mental illnesses. The current study examined United
      States dental professionals' perceptions of dental fear experienced by patients
      with mental illness, and frequency of sedation of patients with and without
      mental illness. Dentists and dental staff members (n = 187) completed a survey
      about their experiences in treating patients with mental illness. More
      participants agreed (79.8%) than disagreed (20.2%) that patients with mental
      illness have more anxiety regarding dental treatment (p < .001) than dental
      patients without mental illness. Further, significantly more participants
      reported mentally ill patients' anxiety is "possibly" or "definitely" a barrier
      to both receiving (96.8%; p < .001) and providing (76.9%; p < .01) dental
      treatment. Despite reporting more fear in these patients, there were no
      significant differences in frequency of sedation procedures between those with
      and without mental illness, regardless of type of sedation (p's > .05). This lack
      of difference in sedation for mentally ill patients suggests hesitancy on the
      part of dental providers to sedate patients with mental illness and highlights a
      lack of clinical guidelines for this population in the US. Suggestions are given
      for the assessment and clinical management of patients with mental illness.

PMID- 24876663
TI  - Assessment of urinary osteopontin in association with podocyte for early
      predication of nephropathy in diabetic patients.
AB  - OBJECTIVES: Microalbuminuria has been clinically used for noninvasive evaluation
      of renal dysfunctions. However, it is a nonspecific marker of diabetic
      nephropathy (DN). METHODS: This study was conducted from March 2012 to April 2013
      at Biochemistry Unit, King Fahd Medical Research Center (KFMRC). In this study,
      urinary osteopontin, podocytes number, and levels of immunoglobulin M (IgM) were
      determined in 60 patients (diabetic normoalbuminuria, diabetic microalbuminuria,
      and nephritic syndrome) compared with healthy subjects. RESULTS: It was found
      that in diabetic microalbuminuria patients have a highly significant increase in
      urinary IgM, osteopontin, and podocyte levels as compared to other groups.
      Nephrotic syndrome patients showed a moderate significant elevation of these
      parameters compared to control subjects. At a given specificity of 97%, podocytes
      yielded the highest sensitivity of all markers, 95.5%. The sensitivity was
      considerably higher compared to IgM and osteopontin. Podocyte number was
      positively correlated with serum IgM and osteopontin (r = 0.63 and 0.56),
      respectively. Its cutoff corresponding to the 10% coefficient of variation was
      most appropriate for early diagnosis of DN. CONCLUSION: Monitoring urinary
      podocyte may provide a noninvasive tool that is a sensitive, accurate, and
      specific biomarker of glomerular injury and can be used in combination with
      osteopontin and IgM to more reliably detect and monitor prognosis.

PMID- 24876664
TI  - Expression of the microtubule-associated protein MAP9/ASAP and its partners AURKA
      and PLK1 in colorectal and breast cancers.
AB  - BACKGROUND: Colorectal and breast cancers are among the most common cancers
      worldwide. They result from a conjugated deficiency of gene maintenance and cell
      cycle control. OBJECTIVE: We investigate the expression of the microtubule
      associated protein MAP9/ASAP and its two partners AURKA and PLK1 in colorectal
      tumors as well as in ductal breast cancers. MATERIALS AND METHODS: 26 colorectal
      cancer samples and adjacent normal tissues and 77 ductal breast cancer samples
      from grade I to grade III were collected. Real-time quantitative PCR was used to
      analyse the expression of MAP9, AURKA, and PLK1. Results. Expression of MAP9 is
      downregulated in colorectal cancer compared to normal tissues (P > 10(-3)),
      whereas those of AURKA and PLK1 are upregulated (P > 10(-4)). In ductal breast
      cancer, we found a grade-dependent increase of AURKA expression (P > 10(-3)),
      while the variations of expression of MAP9 and PLK1 are not significant (P >
      0.2). CONCLUSIONS: MAP9 downregulation is associated with colorectal malignancy
      and could be used as a disease marker and a new drug target, while AURKA and PLK1
      are upregulated. In ductal breast cancer, AURKA overexpression is strongly
      associated with the tumor grade and is therefore of prognostic value for the
      progression of the disease.

PMID- 24876665
TI  - Perseveration found in a human drawing task: six-fingered hands drawn by patients
      with right anterior insula and operculum damage.
AB  - BACKGROUND: Perseveration has been observed in a number of behavioural contexts,
      including speaking, writing, and drawing. However, no previous report describes
      patients who show perseveration only for drawing a human figure. OBJECTIVE: The
      present report describes a group of patients who show body awareness-related
      cognitive impairment during a human figure drawing task, a different presentation
      from previously described neuropsychological cases. METHODS: Participants were 15
      patients who had a frontal lobe brain tumour around the insula cortex of the
      right hemisphere and had subsequently undergone a neurosurgical resective
      operation. Participants were asked to draw a human figure in both "hands-down"
      and "hands-up" configurations. RESULTS: Eight of the 15 patients drew a human
      figure with six fingers during the "hands-up" and the "hands-down" human figure
      drawing tasks (one patient drew eight fingers). A statistical analysis of
      potential lesion areas revealed damage to the right anterior frontal insula and
      operculum in this group of patients relative to the five-finger drawing group.
      CONCLUSIONS: Our findings reveal a newly described neuropsychological phenomenon
      that could reflect impairment in attention directed towards body representations.

PMID- 24876666
TI  - Interaction with mesenchymal stem cells provokes natural killer cells for
      enhanced IL-12/IL-18-induced interferon-gamma secretion.
AB  - Tissue injury induces an inflammatory response accompanied by the recruitment of
      immune cells and of mesenchymal stem cells (MSC) that contribute to tissue
      regeneration. After stimulation with interleukin- (IL-) 12 and IL-18 natural
      killer (NK) cells secrete the proinflammatory cytokine interferon- (IFN-) gamma.
      IFN- gamma plays a crucial role in the defense against infections and modulates
      tissue regeneration. In consideration of close proximity of NK cells and MSC at
      the site of injury we investigated if MSC could influence the ability of NK-cells
      to produce IFN-gamma. Coculture experiments were performed with bone marrow
      derived human MSC and human NK cells. MSC enhanced the ability of IL-12/IL-18
      stimulated NK cells to secrete IFN- gamma in a dose-dependent manner. This
      activation of NK cells was dependent on cell-cell contact as well as on soluble
      factors. The increased IFN- gamma secretion from NK cells after contact with MSC
      correlated with an increased level of intracellular IFN- gamma. Alterations in
      the IL-12 signaling pathway including an increased expression of the IL-12beta1
      receptor subunit and an increased phosphorylation of signal transducer and
      activator of transcription 4 (STAT4) could be observed. In conclusion, MSC
      enhance the IFN- gamma release from NK cells which might improve the defense
      against infections at the site of injury but additionally might affect tissue
      regeneration.

PMID- 24876667
TI  - Chemokines profiling of patients with preterm birth.
AB  - INTRODUCTION: Nowadays it is thought that the main cause of premature birth is
      subclinical infection. However, none of the currently used methods provide
      effective prevention to preterm labor. The aim of the study was to determine the
      concentration of selected chemokines in sera of patients with premature birth
      without clinical signs of infection (n = 62), threatened preterm labor (n = 47),
      and term births (n = 28). METHOD: To assess the concentration of chemokines in
      the blood serum, we used a multiplex method, which allows the simultaneous
      determination of 40 chemokines per sample. The sets consist of the following
      chemokines: 6Ckine/CCL21, Axl, BTC, CCL28, CTACK/CCL27, CXCL16, ENA-78/CXCL5,
      Eotaxin-3/CCL26, GCP-2/CXC, GRO (GRO alpha /CXCL1, GRO beta /CXCL2 and GRO gamma
      /CXCL3), HCC-1/CCL14, HCC-4/CCL16, IL-9, IL-17F, IL18-BPa, IL-28A, IL-29, IL-31,
      IP-10/CXCL10, I-TAC/CXCL11, LIF, LIGHT/TNFSF14, Lymphotactin/XCL1, MCP-2/CCL8,
      MCP-3/CCL7, MCP-4/CCL13, MDC/CCL22, MIF, MIP-3 alpha /CCL20, MIP-3- beta /CCL19,
      MPIF-1/CCL23, NAP-2/CXCL7, MSP alpha , OPN, PARC/CCL18, PF4, SDF-1/CXCL12,
      TARC/CCL17, TECK/CCL25, and TSLP. RESULTS: We showed possible implication of 4
      chemokines, that is, HCC-4, I-TAC, MIP-3 alpha , and TARC in women with symptoms
      of preterm delivery. CONCLUSION: On the basis of our findings, it seems that the
      chemokines may play role in the pathogenesis of preterm labor. Defining their
      potential as biochemical markers of preterm birth requires further investigation
      on larger group of patients.

PMID- 24876668
TI  - Amyloidosis, inflammation, and oxidative stress in the heart of an alkaptonuric
      patient.
AB  - BACKGROUND: Alkaptonuria, a rare autosomal recessive metabolic disorder caused by
      deficiency in homogentisate 1,2-dioxygenase activity, leads to accumulation of
      oxidised homogentisic acid in cartilage and collagenous structures present in all
      organs and tissues, especially joints and heart, causing a pigmentation called
      ochronosis. A secondary amyloidosis is associated with AKU. Here we report a
      study of an aortic valve from an AKU patient. RESULTS: Congo Red birefringence,
      Th-T fluorescence, and biochemical assays demonstrated the presence of SAA
      amyloid deposits in AKU stenotic aortic valve. Light and electron microscopy
      assessed the colocalization of ochronotic pigment and SAA-amyloid, the presence
      of calcified areas in the valve. Immunofluorescence detected lipid peroxidation
      of the tissue and lymphocyte/macrophage infiltration causing inflammation. High
      SAA plasma levels and proinflammatory cytokines levels comparable to those from
      rheumatoid arthritis patients were found in AKU patient. CONCLUSIONS: SAA
      amyloidosis was present in the aortic valve from an AKU patient and colocalized
      with ochronotic pigment as well as with tissue calcification, lipid oxidation,
      macrophages infiltration, cell death, and tissue degeneration. A local HGD
      expression in human cardiac tissue has also been ascertained suggesting a
      consequent local production of ochronotic pigment in AKU heart.

PMID- 24876669
TI  - MicroRNAs involved in the lipid metabolism and their possible implications for
      atherosclerosis development and treatment.
AB  - Hyperlipidemia is a well-accepted risk factor in the development of
      atherosclerosis. MicroRNAs (miRNAs), a novel class of posttranscriptional
      regulators of gene expression, are involved in a variety of biological and
      pathological processes, including the regulation of the lipid metabolism and
      atherosclerosis. As our knowledge of miRNAs expands, a new class of "circulating
      miRNAs" has recently been described. It includes miRNAs which may be found in
      various bodily fluids packaged in microvesicles/exosomes, or bound to specific
      transporting proteins. High-density lipoprotein (HDL) particles have been
      identified as one such carrier. As this class of miRNAs likely plays a role in
      intercellular communication, it may also contribute to the atherosclerosis
      development and progression. This review aims to provide a comprehensive
      explanation of the roles of distinct miRNAs involved in the regulation of the
      lipid metabolism. These microRNAs seem to be promising therapeutic agents, as
      documented in rodents and African green monkeys. The second part of the review
      focuses on circulating miRNAs and their involvement in the atherosclerosis,
      especially as their levels have been described as altered in patients with
      dyslipidemia/hyperlipidemia. Special emphasis is placed on miRNAs transported in
      a complex with HDL particles and on those which may be considered potential
      atherosclerosis biomarkers. 

PMID- 24876670
TI  - Active smoking increases microsomal PGE2-synthase-1/PGE-receptor-4 axis in human
      abdominal aortic aneurysms.
AB  - BACKGROUND: The cyclooxygenase- (COX-) 2/microsomal PGE-synthase- (mPGES-) 1/PGE
      receptor- (EP-) 4 axis could play a key role in the physiopathology of abdominal
      aortic aneurysm (AAA) in humans. In this study, we investigated the influence of
      cardiovascular risk factors on the expression of the PGE2 pathway in human AAA.
      METHODS: Aortic (n = 89) and plasma (n = 79) samples from patients who underwent
      AAA repair were collected. Patients were grouped according to risk factors. COX
      isoenzymes, mPGES-1, EPs, alpha-actin, and CD45 and CD68 transcripts levels were
      quantified by QRT-PCR and plasma PGE2 metabolites by EIA. RESULTS: Current
      smoking (CS) patients compared to no-CS had significantly higher local levels of
      mPGES-1 (P = 0.009), EP-4 (P = 0.007), and PGE2 metabolites plasma levels (P =
      0.008). In the multiple linear regression analysis, these parameters remained
      significantly enhanced in CS after adding confounding factors. Results from
      association studies with cell type markers suggested that the increased mPGES
      1/EP-4 levels were mainly associated with microvascular endothelial cells.
      CONCLUSIONS: This study shows that elements of the PGE2 pathway, which play an
      important role in AAA development, are increased in CS. These results provide
      insight into the relevance of tobacco smoking in AAA development and reinforce
      the potential of mPGES-1 and EP-4 as targets for therapy in AAA patients.

PMID- 24876672
TI  - Subnormal peripheral blood leukocyte counts are related to the lowest prevalence
      and incidence of metabolic syndrome: Tianjin chronic low-grade systemic
      inflammation and health cohort study.
AB  - Few studies have assessed the relationship between a subnormal inflammatory
      status and metabolic syndrome (MS). We therefore designed a cross-sectional and 5
      year cohort study to evaluate how a subnormal peripheral blood leukocyte count is
      related to MS. Participants were recruited from Tianjin Medical University
      General Hospital-Health Management Centre. Both a baseline cross-sectional (n =
      46,179) and a prospective assessment (n = 13,061) were performed. Participants
      without a history of MS were followed up for 5 years. Leukocyte counts and MS
      components were assessed at baseline and yearly during the follow-up. Adjusted
      logistic and Cox proportional hazards regression models were used to assess
      relationships between the categories of leukocyte counts and MS. The subnormal
      leukocyte counts group (1,100-3,900 cells/mm(3)) had the lowest prevalence and
      incidence of MS. The odds ratio and hazard ratio (95% confidence interval) of the
      highest leukocyte counts were 1.98 (1.57-2.49) and 1.50 (1.22-1.84) (both P for
      trend <0.0001), respectively, when compared to the subnormal leukocyte counts
      group after adjusting for potential confounders. This study has shown that
      subnormal leukocyte counts are independently related to the lowest prevalence and
      incidence of MS. The findings suggest that it is necessary to restudy and discuss
      the clinical or preventive value of subnormal leukocyte counts.

PMID- 24876671
TI  - Chrysophanol inhibits NALP3 inflammasome activation and ameliorates cerebral
      ischemia/reperfusion in mice.
AB  - The most effective way to contain cerebral ischemic injury is reperfusion;
      however, reperfusion itself may result in tissue injury, for which inflammatory
      damage is one of the main causative factors. NALP3 inflammasome is a multiprotein
      complex. It consists of NALP3, ASC, and caspase-1, whose function is to switch on
      the inflammatory process. Chrysophanol is an extract from plants of Rheum genus
      and it possesses many pharmacological effects including its anti-inflammation
      activity. In this study, the effects of chrysophanol in cerebral
      ischemia/reperfusion and the potential mechanisms were investigated. Male CD1
      mice were subject to transient middle cerebral artery occlusion (tMCAO). The
      NALP3 inflammasome activation status and its dynamic expression during the
      natural inflammatory response induced by tMCAO were first profiled. The
      neuroprotective effects of chrysophanol were then assessed and the potential
      mechanisms mediating the observed neuroprotection were then explored. Physical
      parameters including neurological deficit, infarct size, brain edema, and BBB
      permeability were measured at 24 h after tMCAO. Confocal microscopy, Western
      blotting, immunohistochemistry, and qRT-PCR techniques were utilized to analyze
      the expression of NALP3 inflammasome and IL-1 beta . Our results indicated that
      the brain tissue damage during cerebral ischemia/reperfusion is accompanied by
      NALP3 inflammasome activation. Chrysophanol could inhibit the activation of NALP3
      inflammasome and protect cerebral ischemic stroke.

PMID- 24876673
TI  - The effects of florfenicol on the values of serum tumor necrosis factor-alpha and
      other biochemical markers in lipopolysaccharide-induced endotoxemia in brown
      trout.
AB  - The aim of the present study was to determine the effects of florfenicol on the
      expected changes in sTNF-alpha, damage markers of the liver and kidney, and the
      lipid metabolism parameters in endotoxemic brown trout. Ninety-six brown trout
      were included in this study. After six of the fish were reserved as the control
      group, the remaining 90 fish were divided equally into 3 groups as follows: LPS
      (2 mg/kg, IP), LPS (2 mg/kg, IP) + florfenicol (40 mg/kg, IM), and florfenicol
      (40 mg/kg, IM). Blood samples were obtained from the tail of the fish at 1.5, 3,
      6, 10, and 24 hours. The levels of sTNF-alpha were determined by ELISA and
      biochemical markers were evaluated with an autoanalyzer. A significant increase
      was observed in the values of sTNF-alpha in the LPS and LPS + florfenicol groups
      (P < 0.05). Significant increases were found in the kidney and liver damage
      determinants in the LPS and LPS + florfenicol groups (P < 0.05). Irregular
      changes in the lipid metabolism parameters were observed in all the subgroups. In
      conclusion, florfenicol does not affect the increases of sTNF-alpha caused by LPS
      and does not prevent liver or kidney damage; at least, it can be said that
      florfenicol does not have any evident positive effects on the acute endotoxemia
      of fish.

PMID- 24876676
TI  - Anti-inflammatory functions of protein C require RAGE and ICAM-1 in a stimulus
      dependent manner.
AB  - By binding beta 2-integrins both ICAM-1 and the receptor for advanced glycation
      end products (RAGE) mediate leukocyte recruitment in a stimulus-dependent manner.
      Using different inflammatory mouse models we investigated how RAGE and ICAM-1 are
      involved in anti-inflammatory functions of protein C (PC; Ceprotin, 100 U/kg). We
      found that, depending on the stimulus, RAGE and ICAM-1 are cooperatively involved
      in PC-induced inhibition of leukocyte recruitment in cremaster models of
      inflammation. During short-term proinflammatory stimulation (trauma, fMLP, and
      CXCL1), ICAM-1 is more important for mediation of anti-inflammatory effects of
      PC, whereas RAGE plays a major role after longer proinflammatory stimulation (TNF
      alpha ). In contrast to WT and Icam-1(-/-) mice, PC had no effect on
      bronchoalveolar neutrophil emigration in RAGE(-/-) mice during LPS-induced acute
      lung injury, suggesting that RAGE critically mediates PC effects during acute
      lung inflammation. In parallel, PC treatment effectively blocked leukocyte
      recruitment and improved survival of WT mice and Icam-1-deficient mice in LPS
      induced endotoxemia, but failed to do so in RAGE-deficient mice. Exploring
      underlying mechanisms, we found that PC is capable of downregulating
      intracellular RAGE and extracellular ICAM-1 in endothelial cells. Taken together,
      our data show that RAGE and ICAM-1 are required for the anti-inflammatory
      functions of PC.

PMID- 24876675
TI  - ADAMTS-12: a multifaced metalloproteinase in arthritis and inflammation.
AB  - ADAMTS-12 is a member of a disintegrin and metalloproteinase with thrombospondin
      motifs (ADAMTS) family of proteases, which were known to play important roles in
      various biological and pathological processes, such as development, angiogenesis,
      inflammation, cancer, arthritis, and atherosclerosis. In this review, we briefly
      summarize the structural organization of ADAMTS-12; concentrate on the emerging
      role of ADAMTS-12 in several pathophysiological conditions, including
      intervertebral disc degeneration, tumorigenesis and angioinhibitory effects,
      pediatric stroke, gonad differentiation, trophoblast invasion, and genetic
      linkage to schizophrenia and asthma, with special focus on its role in arthritis
      and inflammation; and end with the perspective research of ADAMTS-12 and its
      potential as a promising diagnostic and therapeutic target in various kinds of
      diseases and conditions. 

PMID- 24876674
TI  - The role of inflammatory and anti-inflammatory cytokines in the pathogenesis of
      osteoarthritis.
AB  - Osteoarthritis (OA) is the most common chronic disease of human joints. The basis
      of pathologic changes involves all the tissues forming the joint; already, at an
      early stage, it has the nature of inflammation with varying degrees of severity.
      An analysis of the complex relationships indicates that the processes taking
      place inside the joint are not merely a set that (seemingly) only includes
      catabolic effects. Apart from them, anti-inflammatory anabolic processes also
      occur continually. These phenomena are driven by various mediators, of which the
      key role is attributed to the interactions within the cytokine network. The most
      important group controlling the disease seems to be inflammatory cytokines,
      including IL-1 beta , TNF alpha , IL-6, IL-15, IL-17, and IL-18. The second group
      with antagonistic effect is formed by cytokines known as anti-inflammatory
      cytokines such as IL-4, IL-10, and IL-13. The role of inflammatory and anti
      inflammatory cytokines in the pathogenesis of OA with respect to inter- and
      intracellular signaling pathways is still under investigation. This paper
      summarizes the current state of knowledge. The cytokine network in OA is put in
      the context of cells involved in this degenerative joint disease. The
      possibilities for further implementation of new therapeutic strategies in OA are
      also pointed. 

PMID- 24876680
TI  - Proceedings of German Society for Stem Cell Research (PGSSCR).

PMID- 24876679
TI  - Proceedings of the Annual Symposium on Regenerative Medicine(PASRM).

PMID- 24876681
TI  - Python bite: an unusual cause of hand injury.
AB  - We report a patient that sustained a severe hand injury following a python bite.
      Python bite injuries are rare and we were unable to find guidelines in literature
      regarding the management of this injury. This report details our experience in
      managing this case and summarizes the available literature. 

PMID- 24876677
TI  - Evaluation on potential contributions of protease activated receptors related
      mediators in allergic inflammation.
AB  - Protease activated receptors (PARs) have been recognized as a distinctive four
      member family of seven transmembrane G protein-coupled receptors (GPCRs) that can
      be cleaved by certain serine proteases. In recent years, there has been
      considerable interest in the role of PARs in allergic inflammation, the
      fundamental pathologic changes of allergy, but the potential roles of PARs in
      allergy remain obscure. Since many of these proteases are produced and actively
      involved in the pathologic process of inflammation including exudation of plasma
      components, inflammatory cell infiltration, and tissue damage and repair, PARs
      appear to make important contribution to allergy. The aim of the present review
      is to summarize the expression of PARs in inflammatory and structural cells, the
      influence of agonists or antagonists of PARs on cell behavior, and the
      involvement of PARs in allergic disorders, which will help us to better
      understand the roles of serine proteases and PARs in allergy. 

PMID- 24876682
TI  - Diagnosis of carpal tunnel syndrome: interobserver reliability of the blinded
      scratch-collapse test.
AB  - The reliability of the scratch-collapse test for diagnosis of carpal tunnel
      syndrome (CTS) has not been tested by independent investigators. This study
      measured the reliability of the scratch-collapse test comparing the treating hand
      surgeon and blinded evaluators. We performed a prospective observational study of
      41 patients with a provisional diagnosis of CTS or a combination of CTS and
      cubital tunnel syndrome and prescribed electrodiagnostic testing. The treating
      hand surgeon performed the scratch-collapse test. Next, the test was administered
      by one of the six observers, unaware of the patient's symptoms and the diagnosis
      made by treating hand surgeon. The kappa statistic (kappa) was used to calculate
      the interrater reliability between the treating hand surgeons and blinded
      scratchers. The agreement between the blinded observers and the hand surgeons on
      the scratch-collapse test was substantial 0.63 (95 % CI, 0.34-0.87; p < 0.001).
      The sensitivity of the blinded scratch test in our sample was 32 %. In a small
      study with a spectrum bias favoring electrophysiologically confirmed CTS the
      reliability was lower than that reported by the inventors of the test, but was
      still substantial. We propose a larger study of patients with a greater variety
      of electrodiagnostic test results using fewer observers with more experience. 

PMID- 24876683
TI  - A comparison of the reliability of make versus break testing in measuring palmar
      abduction strength of the thumb.
AB  - Previous studies have established the role of quantitative measurements of palmar
      abduction strength of the thumb (PAST). This study compares the reliability of
      the 'make' versus the 'break' test in measuring PAST in healthy volunteers. In a
      'make' test, the body part being tested is positioned at the start of its range
      of motion and the participant is asked to exert his/her maximal force. In a
      'break' test, increasing force is applied to a body part after it has completed
      its range of motion, until the joint being tested gives way. PAST was measured in
      both hands in 100 healthy volunteers using a handheld device. Two examiners
      measured PAST using both the 'make' and 'break' test to determine inter-rater
      reliability. The tests were repeated in 30 volunteers 6 weeks after the initial
      testing to determine intra-rater reliability. Our results showed that the 'make'
      test has better inter and intra-rater reliability. 

PMID- 24876678
TI  - Interaction of dietary fatty acids with tumour necrosis factor family cytokines
      during colon inflammation and cancer.
AB  - Intestinal homeostasis is precisely regulated by a number of endogenous
      regulatory molecules but significantly influenced by dietary compounds.
      Malfunction of this system may result in chronic inflammation and cancer. Dietary
      essential n-3 polyunsaturated fatty acids (PUFAs) and short-chain fatty acid
      butyrate produced from fibre display anti-inflammatory and anticancer activities.
      Both compounds were shown to modulate the production and activities of TNF family
      cytokines. Cytokines from the TNF family (TNF- alpha, TRAIL, and FasL) have
      potent inflammatory activities and can also regulate apoptosis, which plays an
      important role in cancer development. The results of our own research showed
      enhancement of apoptosis in colon cancer cells by a combination of either
      docosahexaenoic acid (DHA) or butyrate with TNF family cytokines, especially by
      promotion of the mitochondrial apoptotic pathway and modulation of NF kappa B
      activity. This review is focused mainly on the interaction of dietary PUFAs and
      butyrate with these cytokines during colon inflammation and cancer development.
      We summarised recent knowledge about the cellular and molecular mechanisms
      involved in such effects and outcomes for intestinal cell behaviour and
      pathologies. Finally, the possible application for the prevention and therapy of
      colon inflammation and cancer is also outlined.

PMID- 24876684
TI  - Diagnostic accuracy of two-dimensional and three-dimensional imaging and modeling
      of radial head fractures.
AB  - To tests the hypothesis that classification and characterization of fractures of
      the radial head is more accurate with 3D than 2D computed tomography images and
      radiographs, using a prospective study design with intraoperative inspection as
      the reference standard. Treating surgeons and first assistants completed a
      questionnaire assigning a fracture type according to the Broberg and Morrey
      modification of Mason's classification, evaluating selected fracture
      characteristics, and electing preferred management based upon radiographs and 2D
      images alone; then adding 3D-CT; then 3D printed physical models; and finally
      intra-operative visualization. The addition of the 3D CT and physical models
      improved the sensitivity for fracture line separating the entire head from the
      neck, comminution of the radial neck, fracture involving the articular surface,
      articular fracture gap greater than 2 mm, impacted fracture fragments, greater
      than 3 articular fragments, and articular fragments judged too small to repair.
      There were no significant differences in diagnostic performance with the addition
      of 3D models. The addition of 3D CT and models improved the reliability of
      Broberg and Morrey classification. We conclude that 3DCT and 3D physical modeling
      provide more accurate fracture classification and characterization of fracture of
      the radial head with less proposed variability in treatment. We did not
      demonstrate a clear advantage for modeling over 3DCT reconstructions. LEVEL OF
      EVIDENCE: Diagnostic, Level I.

PMID- 24876686
TI  - A simple method for identifying the acromioclavicular joint during arthroscopic
      procedures.
AB  - Arthroscopic acromioclavicular joint excision is performed via an anterior portal
      and is technically demanding. We present a simple method for identifying the
      acromioclavicular joint during arthroscopic procedures. 

PMID- 24876685
TI  - The pisotriquetral joint: osteoarthritis and enthesopathy.
AB  - Pisotriquetral (PT) osteoarthritis (OA) and enthesopathy of the flexor carpi
      ulnaris (FCU) are pathologies of the hypothenar eminence which both often remain
      undiagnosed, but can cause ulnar wrist pain. This study determined the prevalence
      of these pathologies in an older donor population. Twenty wrists were obtained
      from 10 cadavers with an age ranging from 65 to 94 years. Radiographs were taken
      of all wrists with the hand in pisotriquetral view and were assessed for
      osteoarthritic changes of the PT joint and signs of enthesopathy of the FCU. Ten
      wrists were grossly dissected and the other ten wrists were sagitally sectioned
      at a thickness of 10 MUm. The wrists were analyzed for type and grade of
      osteoarthritis and signs of enthesopathy. On radiology, 2 out of 20 wrists showed
      no signs of osteoarthritis, 5 wrists showed severe changes. One wrist showed
      signs of enthesopathy. On macroscopy, 9 out of 10 wrists showed osteoartritic
      changes; 5 of these were severely osteoarthritic. On microscopy, all wrists
      showed some degree of osteoarthritis of which five showed severe changes. Signs
      of enthesopathy were seen in seven wrists. Pisotriquetral osteoarthritis has a
      high prevalence in the older donor population and may therefore be a cause of
      ulnar sided wrist pain. It should therefore always be considered in the
      differential diagnosis of ulnar sided wrist pain. By performing clinical
      examination with these pathologies in mind, diagnosis could be a lot faster.
      Furthermore, based on our results, radiographs seem to be not accurate in
      diagnosing osteoarthritis of the PT joint and enthesopathy of the FCU. 

PMID- 24876688
TI  - Variable presentation of brachioradialis muscle during radial artery forearm free
      flap harvest-an accessory distal belly.

PMID- 24876687
TI  - Evaluation of Non Diseased Specified Outcome Measures in Hand Injuries to Assess
      Activity and Participation Based on ICF Content.
AB  - The objective of the study is to provide information about non disease specified
      outcome measures which evaluate disability in patients who have impairments in
      hand and upper extremity and to find the extent to which they are evaluating
      "disability" based on ICF hand Core Set (activity limitation and participation
      restriction). MEDLINE, CINAHL, GOOGLE SCHOLAR , OVID and SCIENCE DIRECT databases
      were systematically searched for studies on non disease specified outcome
      measures used to evaluate upper extremity function; only studies written in
      English were considered. We reviewed titles and abstracts of the identified
      studies to determine whether the studies met predefined eligibility criteria (eg,
      non disease specified out come measures used in hand injured patients). All the
      outcome measures which had eligibility included. After full text review ,7 non
      disease specified outcome measures in hand were identified. Studies were
      extracted, and the information retrieved from them. All the outcome measures
      which had incuded, were linked with ICF hand core set disability part (activity
      and participation). All of them only linked to 16 (42 %) components of ICF hand
      Core Set, which were most activity and less participation from ICF. None of the
      non disease specified out come measures in hand injuries cover all domains of
      disability from the ICF Hand Core Set. 

PMID- 24876689
TI  - Global reconstruction of the flexor apparatus after wide local excision of a
      recurrent diffuse giant cell tumor of the hand: a case report and literature
      review.

PMID- 24876690
TI  - Fibrochondroma of Digital Flexor Tendon Sheath-a Rare Presentation.

PMID- 24876691
TI  - How to kill a flap: munchausen syndrome - a silent trap for plastic surgeons.

PMID- 24876692
TI  - Angioleiomyoma of middle finger terminal phalanx-case report and review of
      literature.

PMID- 24876693
TI  - Absent palmar cutaneous branch of median nerve.

PMID- 24876694
TI  - Mid-axial injection of steroid into the flexor sheath for trigger fingers.

PMID- 24876695
TI  - Impact of Bisphosphonate on Orthodontic tooth movement and osteoclastic count: An
      Animal Study.
AB  - Background : The aim of the current study is to examine the effect of
      systemically administered BP-Pamidronate, on Orthodontic Tooth Movement (OTM)
      along with osteoclastic quantification in New Zealand white rabbits. Materials &
      Methods : Twenty rabbits used in the study, were equally divided into 2 groups ;
      Group-1 as Control & Group-2 as Experimental. A sentalloy NITI closed coil spring
      (GAC International, USA) of 100 gram force, ligated between the lower first molar
      and the anterior most incisors of the rabbit has served as orthodontic force
      element. The BP- Pamidronate was administered at the dosage of 1.5 mg/kg body
      intra-peritonially, on the 1st, 7th and 14th day of the experiment. On the 21st
      day both group of animals were sacrificed, mandibles were dissected. The formed
      diastema between the 1st and 2nd molar was measured on the dissected mandibles
      using standard metric scale, which is considered as the OTM in the mesial
      direction. Next, the alveolar bone regions along with intact mesial surfaces were
      processed for histological investigation (osteoclastic count). Results : The
      student 't' test has been done to compare the mean values of molar tooth movement
      and osteoclastic count. Parameter :1 molar tooth movement has shown a significant
      difference between the control (3.750 +/- 0.548 mm) and the experimental group
      (3.050 +/- 0.556 mm) with calculated 'p' value (p-value <0.05) is significant at
      0.0110 level. Parameter : 2 osteoclastic count has shown a significant difference
      between the control (13.335000 +/- 0.735856 per square mm.) and the experimental
      group (11.426900 +/- 1.49369 per square mm) calculated 'p' value (p-value <0.05)
      is significant at 0.003 level. Conclusion : The molar tooth movement and the
      osteoclastic count were significantly reduced in BP - Pamidronate administered
      animals than non-drug recipients. How to cite the article: Venkataramana V,
      Chidambaram S, Reddy BV, Goud EV, Arafath M, Krishnan S. Impact of Bisphosphonate
      on Orthodontic tooth movement and olsteoclastic count: An Animal Study. J Int
      Oral Health 2014;6(2):1-8. 

PMID- 24876696
TI  - Mandibular third molar impactions in male adults: Relationship of Operative time
      and Types of impaction on inflammatory complications.
AB  - BACKGROUND: This paper investigates the relationship betweendifferent types of
      impactions with postoperativeinflammatory tissue reaction. MATERIALS & METHODS:
      Consecutive patients with only mandibular third molar impactions were included in
      our study. They were classified by winter's classification. The disimpactions
      were performed under local anaesthesia. Time for surgery was noted for each
      surgical procedure. Postoperative inflammatory complication in terms of pain,
      swelling and trismus were noted. RESULTS: 150 male patients in the age groupof 18
      40 years were studied. Inflammatory tissue reactions were increasing with more
      operative time. Distoangular and Horizontal impactions were associated with more
      pain on first 3 days of surgery along with more swelling and trismus. Vertically
      impacted teeth were associated with least complications. CONCLUSION: Post
      operative morbidity was increasing along with moreoperating time and increase in
      the depth of mandibular third molar impaction. How to cite the article: Mansuri
      S, Mujeeb A, Hussain SA, Hussain MA. Mandibular third molar impactions in male
      adults: Relationship of Operative time and Types of impaction on inflammatory
      complications. J Int Oral Health 2014;6(2):9-15.

PMID- 24876697
TI  - Comparison of anchorage loss following initial leveling and aligning using ROTH
      and MBT Prescription - A clinical prospective study.
AB  - BACKGROUND: To evaluate the amount and percentage of anchor loss after initial
      leveling and aligning using a ROTH and MBT prescription. MATERIALS & METHODS: Pre
      and post alignment lateral cephalograms & dental casts of 10 ROTH & 10 MBT
      patients. RESULTS: In the study, it was found that the amount of anchor loss is
      greater in the ROTH group than the MBT group. This could be due to the increased
      anterior tip in the ROTH prescription, compared to MBT. The total anterior tip in
      ROTH is 270 and in MBT is 200. The additional tip of 70 in ROTH prescription
      itself would have resulted in forward thrust of the anteriors. CONCLUSION: The
      use of laceback and cinchbacks creates a statistically and clinically significant
      increase in the anchorage loss specifically when the posterior anchorage is not
      enhanced. In this study TPA was not used but studies have shown that passive TPA
      has almost no effect on the clinician's need to preserve anchorage in the
      correction of malocclusion. On the other hand, the TPA is an excellent way to
      prevent molar rotation and maintain the original vertical and transverse
      dimension when desired. How to cite the article: Rajesh M, Kishore MS, Shetty KS.
      Comparison of anchorage loss following initial leveling and aligning using ROTH
      and MBT Prescription - A clinical prospective study. J Int Oral Health
      2014;6(2):16-21.

PMID- 24876698
TI  - An in-vitro evaluation of effect of EDTAC on root dentin with respect to time.
AB  - BACKGROUND: The present study was devised to evaluate the effects of 17% EDTAC on
      smear layer removal and on the dentin structure after irrigation with 1 minute
      and 10 minutes. MATERIALS & METHODS: One hundred extracted mandibular molars with
      two separate mesial canals were selected; mesiobuccal canal was instrumented to
      size 30 file with crown down technique. One half of each root (either mesial or
      distal) was randomly selected and prepared for scanning electron microscopic
      (SEM) evaluation that was then cut longitudinally into two equal segments. Using
      10 ml of 17% EDTA solution, halves belonging to the same root were irrigated for
      1 and 10 min, respectively. All specimens were subjected to irrigation with 10 ml
      of 5% NaOCl. Then all the specimens were prepared for SEM evaluation. RESULTS:
      The results showed that 1 min EDTA irrigation is effective in removing the smear
      layer. However a 10-min application of EDTA caused excessive peritubular and
      intertubular dentinal erosion. CONCLUSION: Therefore we suggest that this
      procedure should not be prolonged >1 min during endodontic treatment. How to cite
      the article: Darda S, Madria K, Jamenis R, Heda A, Khanna A, Sardar L. An in
      vitro evaluation of effect of EDTAC on root dentin with respect to time. J Int
      Oral Health 2014;6(2):22-7.

PMID- 24876699
TI  - Post-Obturation pain following one-visit and two-visit root canal treatment in
      necrotic anterior teeth.
AB  - BACKGROUND: To investigate and compare the post-obturation pain after one-visit
      and two-visit root canal treatment in non-vital anterior teeth. MATERIALS &
      METHODS: One hundred forty eight patients requiring root canal therapy on
      permanent anterior non-vital teeth with single root were included in this study.
      Patients were randomly assigned to either the one-appointment or the
      twoappointment group. The standardized protocol for all the teeth involved local
      anesthesia, isolation and access, engine-driven rotary nickel-titanium canal
      instrumentation with 2.5% NaOCl irrigation and obturation. Teeth in group 1 (n =
      74) were obturated during the first appointment by using laterally condensed
      gutta-percha and resin sealer. Teeth in group 2 (n = 74) were given closed
      dressing and were obturated during the second appointment, 7 to 14 days later. A
      modified Visual Analogue Scale was used to measure pain after 6 hours, 24 hours,
      48 hours and 7 days after the treatment. Statistical analysis was done to compare
      groups at each interval by using an independent-samples t test. RESULTS: The
      incidence and intensity of post-obturation pain in both Group 'A' and Group 'B'
      gradually reduced over the study period. When the incidence of pain was compared
      in the single and two visit group, it was found that the single-visit group
      experienced slightly less pain than the two-visit group during all study
      intervals, but the difference found was not statistically significant.
      CONCLUSION: There was no difference in postoperative pain between patients
      treated in only one appointment and patients treated in two appointments. The
      majority of patients in both groups reported no pain or only minimal pain after 7
      days of treatment. How to cite the article: Rao KN, Kandaswamy R, Umashetty G,
      Rathore VP, Hotkar C, Patil BS. Post-Obturation pain following one-visit and two
      visit root canal treatment in necrotic anterior teeth. J Int Oral Health
      2014;6(2):28-32.

PMID- 24876700
TI  - Serum lipid profile in oral precancer and cancer: a diagnostic or prognostic
      marker?
AB  - BACKGROUND: Changes in lipid profile have been associated with malignancy because
      of their key role in the maintenance the integrity of the cell membrane. This
      study evaluated the alterations in serum lipid profile in untreated patients of
      oral submucus fibrosis (OSMF), oral leukoplakia, and oral lichen planus and
      proven cases of oral cancer with respect to healthy controls. MATERIALS &
      METHODS: In this case control study, 20 clinically and histopathologically proven
      patients of oral precancer and oral cancer each were compared with 20 healthy
      controls. In these groups, serumlipids including: (i) Total cholesterol. (ii)
      Triglycerides (TGL). (iii) High density lipoprotein cholesterol (HDL), low
      density lipoprotein cholesterol (LDL) and very low density lipoprotein
      cholesterol (VLDL) were analyzed. RESULTS: Decrease in plasma total cholesterol,
      triglycerides, HDL, LDL, VLDL in the subjects with the oral precancer and oral
      cancer as compared to the controls was statistically significant. There was also
      decrease in plasma levels of TGL and VLDL in oral cancer subjects as compared to
      precancer subjects. Thus, it was found that there is an inverse relationship
      between plasma lipid levels and patients. CONCLUSION: Post operative morbidity
      was increasing along with more operating time and increase in the depth of
      mandibular third molar impaction. How to cite the article: Garg D, Sunil MK,
      Singh PP, Singla N, Rani SR, Kaur B. Serum lipid profile in oral precancer and
      cancer: a diagnostic or prognostic marker? J Int Oral Health 2014;6(2):33-9.

PMID- 24876701
TI  - Modified stethoscope for auscultation of temporomandibular joint sounds.
AB  - BACKGROUND: Purpose of this study was to modify the stethoscope which can
      auscultate the temporomandibular joint (TMJ) sounds more precisely than
      conventional stethoscope, and fabrication of stethoscope compatible software
      which analyses the auscultated sound and gives documentary evidence of that
      analysis in the form of graph. MATERIALS & METHODS: The conventional stethoscope
      was modified by attaching a custom made soundscope with a recording device which
      can be placed in external auditory meatus (EAM) for auscultation of TMJ sounds.
      When this small and smooth end of custom made soundscope of modified stethoscope
      is placed in EAM & connected with specially developed software it records the TMJ
      sounds & analyzes them in form of graph. RESULTS: Fabrication of modified
      stethoscope with software records the auscultated sound as a sound wave in form
      of graph and analyses this sound wave graph to give graphic evidence of prominent
      intensity at prominent frequency as spectrum analysis graph, and duration of that
      sound as a sound length graph. CONCLUSION: The use of modified stethoscope with
      software increases the accuracy of auscultation of TMJ sounds without any
      patient's discomfort and helps in diagnosis of TMJ disorders. The modified
      stethoscope with software for auscultation of TMJ sounds results in more precise
      auscultation & analysis of TMJ for sounds even of low intensity & frequency. How
      to cite the article: Dagar SR, Turakiya V, Pakhan AJ, Jaggi N, Kalra A, Vaidya V.
      Modified stethoscope for auscultation of temporomandibular joint sounds. J Int
      Oral Health 2014;6(2):40-4.

PMID- 24876702
TI  - An evaluation of the position of the neutral zone in relation to the crest of
      mandibular alveolar ridge - An In-vivo study.
AB  - BACKGROUND: In view of the importance of neutral zone in complete denture
      construction, it was thought feasible to determine the relation between the
      centre of the alveolar ridge crest in relation to the neutral zone in a
      buccolingual direction which will help in positioning of the teeth in a region of
      minimum conflict so that the stability of the denture is enhanced. MATERIALS &
      METHODS: The position of the neutral zone to alveolar ridge crest was
      investigated in 30 edentulous patients comprising of both males and females
      divided into three groups, Group I consisted of ten patients whose period of
      edentulousness varied from 0-4 years. Group II included ten patients who were
      edentulous for more than 4 years but less than 8 years. Group III consisted of
      ten patients whose period of edentulousness varied between 8-12 years. One-way
      ANOVA test and multiple comparisons by bonferroni post-hoc tests were used to
      analyze the results and the significance was tabulated. RESULTS: The results of
      the present study state that the neutral zone serves as a guide and suggests that
      the period of edentulousness should be considered while arranging the teeth for
      complete dentures. CONCLUSION: The findings of the current study may serve as an
      important guide in arrangement of teeth for complete denture prosthesis and would
      help to determine the correlation between the neutral zone in relation to the
      crest of the alveolar ridge and the period of edentulousness. How to cite the
      article: Bhorgonde D, Nandakumar K, Khurana PR, Kumari VS, Reddy MS, Siddique S.
      An evaluation of the position of the neutral zone in relation to the crest of
      mandibular alveolar ridge - An In-vivo study. J Int Oral Health 2014;6(2):45-54.

PMID- 24876704
TI  - Use of cortical bone screws in maxillofacial surgery - a prospective study.
AB  - BACKGROUND: The aim of this study is to evaluate the various applications of
      cortical bone screws in oral and maxillofacial surgery. MATERIALS & METHODS: The
      study was conducted in a teaching hospital located in, Bangalore, India, on 20
      patients. These patients were categorized into three groups depending on the
      applications of these screws like, for achieving intermaxillary fixation in Group
      1, for treatment of simple, undisplaced fractures by "Tension wire" method in
      Group-2, and further application of these screws were evaluated in Group-3.
      Different parameters were used to evaluate the efficacy of these screws. RESULTS:
      In Group-1(n=12) there was satisfactory occlusion in all the patients with
      minimal incidence of complications. In Group-2 (n=4) post-operative reduction and
      fixation was satisfactory and in Group-3 (n=4) the function of these screws was
      satisfactory when it was used for vestibuloplasty and also as a suspension wiring
      in treatment of comminuted fracture of zygoma with minimal incidence of
      complications. CONCLUSION: Use of cortical bone screws is a valid alternative for
      achieving intermaxillary fixation, reduction and fixation of simple, undisplaced
      or minimally displaced fractures through Tension wire method owing to its
      simplicity, economy and ease of use, and as a fixation method for apically
      positioned flap in vestibuloplasty procedure. How to cite the article: Satish M,
      Rahman NM, Reddy VS, Yuvaraj A, Muliyar S, Razak PA. Use of Cortical Bone Screws
      in Maxillofacial Surgery - A Prospective Study. J Int Oral Health 2014;6(2):62-7.

PMID- 24876703
TI  - Tensile and shear bond strength of hard and soft denture relining materials to
      the conventional heat cured acrylic denture base resin: An In-vitro study.
AB  - BACKGROUND: The condition of the denture bearing tissues may be adversely
      affected by high stress concentration during function. Chairside Denture (Hard
      and Soft) reliners are used to distribute forces applied to soft tissues during
      function. Tensile and shear bond strength has been shown to be dependent on their
      chemical composition. A weak bond could harbor bacteria, promote staining and
      delamination of the lining material. To investigate tensile and shear bond
      strength of 4 different commercially available denture relining materials to
      conventional heat cured acrylic denture base resin. MATERIALS & METHODS: 4 mm
      sections in the middle of 160 Acrylic cylindrical specimens (20 mm x 8 mm) were
      removed, packed with test materials (Mollosil, G C Reline Soft, G C Reline Hard
      (Kooliner) and Ufi Gel Hard and polymerized. Specimens were divided into 8 groups
      of 20 each. Tensile and shear bond strength to the conventional heat cured
      acrylic denture base resin were examined by Instron Universal Tensile Testing
      Machine using the equation F=N/A (F-maximum force exerted on the specimen
      (Newton) and A-bonding area= 50.24 mm2). One-way ANOVA was used for multiple
      group comparisons followed by Bonferroni Test and Hsu's MCB for multiple pairwise
      comparisons to asses any significant differences between the groups. RESULTS: The
      highest mean Tensile bond strength value was obtained for Ufi Gel Hard (6.49+0.08
      MPa) and lowest for G C Reline Soft (0.52+0.01 MPa). The highest mean Shear bond
      strength value was obtained for Ufi Gel Hard (16.19+0.1 MPa) and lowest for
      Mollosil (0.59+0.05 MPa). The Benferroni test showed a significant difference in
      the mean tensile bond strength and the mean shear bond strength when the two
      denture soft liners were compared as well as when the two denture hard liners
      were compared. Hsu's MCB implied that Ufi gel hard is better than its other
      closest competitors. CONCLUSION: The Tensile and Shear bond strength values of
      denture soft reliners were significantly lower than denture hard reliners. How to
      cite the article: Lau M, Amarnath GS, Muddugangadhar BC, Swetha MU, Das KA.
      Tensile and shear bond strength of hard and soft denture relining materials to
      the conventional heat cured acrylic denture base resin: An In-vitro study. J Int
      Oral Health 2014;6(2):55-61.

PMID- 24876705
TI  - A comparative evaluation of the dimensional accuracy of heat polymerised PMMA
      denture base cured by different curing cycles and clamped by R S technique and
      conventional method - An In-vitro study.
AB  - BACKGROUND: The aim of this study is to evaluate the dimensional accuracy of heat
      polymerized PMMA denture base clamped by the conventional method and by R.S
      technique and cured by a different curing cycle. MATERIALS & METHODS: In this
      study, a total of 40 standardized maxillary record bases were fabricated with
      seven reference points: Point A - Incisive papilla, Point B & C - Canine region
      on either side, Point E & G - Midpoint of tuberosities on either side, Point F-
      Midpoint of the line joining the two tuberosities, Point D- Midpoint between the
      line joining A and F. Group A: Ten maxillary record bases were fabricated by
      conventional clamping method and cured by long curing cycle. Group A1: Ten
      maxillary record bases were fabricated by R.S tension clamping method and cured
      by long curing cycle. Group B: Ten maxillary record bases were fabricated by
      conventional clamping method and cured by short curing cycle. Group B1: Ten
      maxillary record bases were fabricated by R.S tension clamping method and cured
      by short curing cycle. The distances between the reference points i.e. A-B, A-C,
      A-D, D-F, B-E, C-G, E-F, F-G, B-D, D-G, CD, D-E of all three thermoplastic
      denture base plates were measured and recorded with the help of a travelling
      microscope and were used for comparison with the measured and recorded readings
      of processed acrylic denture bases. The data obtained was analyzed by using the
      One Way Analysis of Variance. RESULTS: The overall results of the in vitro study
      indicate that among all the PMMA bases cured by the two clamping systems and the
      different curing cycle, group A' was the most dimensionally stable, followed by
      control group A, then followed by B' and B was most unstable. CONCLUSION: The
      study concluded that the denture bases fabricated by the R.S Technique using the
      long curing cycle would produce the most dimensionally stable PMMA denture bases.
      How to cite the article: Babu MR, Rao CS, Ahmed ST, Bharat JS, Rao NV, Vinod V. A
      comparative evaluation of the dimensional accuracy of heat polymerised PMMA
      denture base cured by different curing cycles and clamped by R S technique and
      conventional method - An In-vitro study. J Int Oral Health 2014;6(2):68-75.

PMID- 24876706
TI  - A comparative study to evaluate the effects of ligation methods on friction in
      sliding mechanics using 0.022" slot brackets in dry state: An In-vitro study.
AB  - BACKGROUND: Friction between archwires and brackets is assuming greater
      importance for finishing with increased use of sliding mechanics in orthodontics
      as friction impedes the desired tooth movement. The following study is conducted
      to compare and evaluate the effect of ligation on friction in sliding mechanics
      using 0.022" slot bracket in dry condition. MATERIALS & METHODS: In the study 48
      combinations of brackets, archwires and different ligation techniques were tested
      in order to provide best combination that offers less friction during sliding
      mechanics. Instron- 4467 machine was used to evaluate static and kinetic friction
      force values and the results were subjected to Statistical Analysis and Anova
      test. RESULTS: The results of the study showed that 0.022" metal brackets,
      Stainless steel wires and Slick modules provided the optimum frictional
      resistance to sliding mechanics. It is observed that frictional forces of 0.019"
      x 0.025" were higher when compared with 0.016" x 0.022" Stainless steel archwire
      due to the increase in dimension. Self-ligating brackets offered least friction
      followed by mini twin, variable force, regular stainless steel, ceramic with
      metal insert bracket and ceramic brackets. The stainless steel ligature offered
      less resistance than slick and grey modules, and TMA wires recorded maximum
      friction. CONCLUSION: The stainless steel archwire of 0.019" x 0.025" dimension
      are preferred during sliding mechanics, these archwires with variable force
      brackets ligated with Slick Modules offer decreased friction and is cost
      effective combination which can be utilized during sliding mechanics. How to cite
      the article: Vinay K, Venkatesh MJ, Nayak RS, Pasha A, Rajesh M, Kumar P. A
      comparative study to evaluate the effects of ligation methods on friction in
      sliding mechanics using 0.022" slot brackets in dry state: An In-vitro study. J
      Int Oral Health 2014;6(2):76-83.

PMID- 24876707
TI  - Comparative evaluation of Shear bond strength of different Pit and fissure
      Sealants in Primary and Permanent teeth - An In-Vitro Study.
AB  - BACKGROUND: Dental caries among children is one of the greatest challenges faced
      by dentists globally; especially that of susceptible surfaces like the Pit and
      fissures. Dental sealants have proved to be an effective way to prevent caries
      development. The Clinical success of any material depends upon its adhesion to
      tooth structure, resistance to wear and ability to withstand the masticatory or
      occlusal forces. Hence it is important to evaluate the shear bond strength (SBS).
      The Present study's aim was to evaluate and compare the shear bond strength of
      different pit and fissure sealants placed on Primary molars and Permanent
      Premolars. MATERIALS & METHODS: Sixty noncarious extracted teeth comprising of
      thirty Primary molars and thirty Permanent Premolars were divided into four
      groups of 15 each. The buccal surfaces of all teeth were dried, etched and the
      etched surfaces of Primary molars (Group I) and Permanent Premolars (Group III)
      were placed with Helioseal-F while Groups II and IV, that included Primary molars
      and Permanent Premolars received Clinpro. Shear bond strength was evaluated and
      the mean was obtained for all the groups. The results were analyzed using twoway
      analysis of variance followed by Tukeys post hoc procedure to check for
      significant differences. RESULTS: The specimens of unfilled sealant Clinpro
      (Groups II & IV) showed higher Shear bond strength when compared to the specimens
      of filled sealant Helioseal-F (Groups I & III). CONCLUSION: The unfilled sealant
      showed a better Shear bond strength compared to the filled sealant. The bond
      strength in Primary molars was slightly higher compared to Permanent Premolars.
      How to cite the article: Pushpalatha HM, Ravichandra KS, Srikanth K, Divya G,
      Done V, Krishna KB, Patil V. Comparative evaluation of Shear bond strength of
      different Pit and fissure Sealants in Primary and Permanent teeth - An In-Vitro
      Study. J Int Oral Health 2014;6(2):84-9.

PMID- 24876708
TI  - Evaluation of efficacy of combinations of five endodontic sealers with five
      antibiotics against Enterococcus Faecalis - An in-vitro study.
AB  - BACKGROUND: To evaluate and compare in vitro the antibacterial efficacy of five
      antibiotics when added individually to five endodontic sealers against
      Enterococcus faecalis (EF). MATERIALS & METHODS: This controlled trial with
      systematic allocation method was carried out to detect the combined antibacterial
      activity of five endodontic sealers (Kerr sealer EWT, Endomethasone, AH26, AH
      Plus, Roekoseal) with five antibiotics regularly used (Amoxicillin,
      metronidazole, azithromyacin, gatifloxacin, doxycycline) on EF. For each
      sealerantibiotic combinations, thirty BHI agar plates (15 aerobic and 15
      anaerobic) were inoculated with EF, containing five sterile paper discs- three of
      various sealer- antibiotic combinations, one of sealer alone (positive control) &
      plain disc as negative control were incubated at 370C for 48 hrs and the zone of
      inhibition was measured. Data analysis was done by ANOVA and Tukey's post- hoc
      test using SPSS( version 17). RESULTS: The findings of this study revealed that
      sealer-antibiotic combination containing amoxicillin had the significant
      difference (p<0.001) in the mean zone of inhibition compared to other
      combinations. Metronidazole showed the minimum zone of inhibition among used
      antibiotics. The sealers in the decreasing order according to their effectiveness
      on EF were Kerr sealer endomethasone, AH26, Rockseal, AH plus. CONCLUSION:
      Addition of antibiotics to endodontic sealers enhances their antibacterial
      activity against Enterococcus faecalis. How to cite the article: Sharma D, Grover
      R, Pinnameneni PS, Dey S, Raju PR. Evaluation of efficacy of combinations of five
      endodontic sealers with five antibiotics against Enterococcus Faecalis - An in
      vitro study. J Int Oral Health 2014;6(2):90-5.

PMID- 24876709
TI  - Elasticity in Elastics-An in-vitro study.
AB  - BACKGROUND: Orthodontic tooth movement results from application of forces to
      teeth. Elastics in orthodontics have been used both intra-orally and extra-
      orally to a great effect. Their use, combined with good patient co-operation
      provides the clinician with the ability to correct both anteroposterior and
      vertical discrepancies. Force decay over a period of time is a major problem in
      the clinical usage of latex elastics and synthetic elastomers. This loss of force
      makes it difficult for the clinician to determine the actual force transmitted to
      the dentition. It's the intent of the clinician to maintain optimal force values
      over desired period of time. The majority of the orthodontic elastics on the
      market are latex elastics. Since the early 1990s, synthetic products have been
      offered in the market for latex-sensitive patients and are sold as nonlatex
      elastics. There is limited information on the risk that latex elastics may pose
      to patients. Some have estimated that 0.12-6% of the general population and 6.2%
      of dental professionals have hypersensitivity to latex protein. There are some
      reported cases of adverse reactions to latex in the orthodontic population but
      these are very limited to date. Although the risk is not yet clear, it would
      still be inadvisable to prescribe latex elastics to a patient with a known latex
      allergy. To compare the in-vitro performance of latex and non latex elastics.
      MATERIALS & METHODS: Samples of 0.25 inch, latex and non latex elastics (light,
      medium, heavy elastics) were obtained from three manufacturers (Forestadent, GAC,
      Glenroe) and a sample size of ten elastics per group was tested. The properties
      tested included cross sectional area, internal diameter, initial force generated
      by the elastics, breaking force and the force relaxation for the different types
      of elastics. Force relaxation testing involved stretching the elastics to three
      times marketed internal diameter (19.05 mm) and measuring force level at
      intervals over a period of 48 hours. The data were analyzed with student
      independent - t test, analysis of variance and the Tukey - HSD test at p <0.05
      level of significance. RESULTS: Non latex elastics had greater cross sectional
      area than latex elastics in all types of elastics. Forestadent heavy elastics had
      grater cross sectional area than GAC and Glenroe. There was no statistically
      significant difference in the internal diameter in between all type of elastics.
      Forestadent non latex elastics had greater breaking force compared to GAC and
      Glenroe elastics. Forces generated by the elastics decreased over 48 hours to an
      average load approximating 65-75% of the manufacturer's values. Force degradation
      was greater in non latex elastics compared to latex elastics. CONCLUSION: The
      results of the study demonstrated that the clinical choice of elastics should be
      based on the patient's medical history and the specific mechanical properties of
      the type of elastic. How to cite the article: Kamisetty SK, Nimagadda C, Begam
      MP, Nalamotu R, Srivastav T, Shwetha GS. Elasticity in Elastics-An in-vitro
      study. J Int Oral Health 2014;6(2):96-105.

PMID- 24876711
TI  - Saliva: A tool in assessing glucose levels in Diabetes Mellitus.
AB  - BACKGROUND: Diabetes mellitus is a metabolic disorder affecting people worldwide,
      which require constant monitoring of their glucose levels. Commonly employed
      procedures include collection of blood or urine samples causing discomfort to the
      patients. Hence the need for an alternative non invasive technique is required to
      monitor glucose levels. Saliva present in the oral cavity not only maintains the
      health of the oral cavity but plays a important role in diagnosis of cancers of
      the oral cavity, periodontal diseases, HIV, heart diseases etc. The aim of the
      present study was undertaken to correlate the glucose levels in saliva and blood
      of diabetic and healthy non diabetic individuals and to determine the efficacy of
      saliva as a diagnostic tool. MATERIALS & METHODS: A total of 30 individuals of
      which 20 patients were diabetic patients and on medication and 10 patients were
      healthy non diabetic individuals were included in the study. Blood and saliva
      were collected under resting conditions and were subjected to glucose estimation.
      RESULTS: Salivary and blood glucose concentrations were determined in non
      diabetic healthy individuals (n=10) and Type II Diabetes mellitus patients
      (n=20). Glycosylated haemoglobin A1c was also determined in both Type II diabetic
      patients and Control group and a significant correlation (r=0.73) and (r=0.46)
      was found between HbA1c and serum glucose concentrations in diabetic and control
      group respectively. A significant correlation (r=0.54) and (r=0.45) was found
      between fasting blood glucose and fasting salivary glucose for diabetic group and
      control group respectively. A positive correlation (r=0.39) and (r=0.38) was
      found between fasting salivary glucose and HbA1c for diabetic and control group
      respectively. CONCLUSION: These findings suggest that the saliva can be used in
      the assessment of the blood glucose concentration in diabetes mellitus patients.
      How to cite the article: Satish BN, Srikala P, Maharudrappa B, Awanti M, Kumar P,
      Hugar D. Saliva: A tool in assessing glucose levels in Diabetes Mellitus. J Int
      Oral Health 2014;6(2):114-7.

PMID- 24876710
TI  - Dento-Alveolar distraction osteogenesis using rigid intra-oral tooth borne
      distraction device.
AB  - BACKGROUND: The aim of this clinical prospective study is to apply and evaluate
      an approach to reduce the overall orthodontic treatment time, by means of
      dentoalveolar distraction osteogenesis to achieve rapid canine retraction using
      an indigenously developed intra-oral tooth-borne distraction device. MATERIALS &
      METHODS: This study was carried out in the Department of Orthodontics and
      Dentofacial Orthopedics. Four patients selected for the purpose of Maxillary
      and/or Mandibular canine distraction with a rigid custom-made, intra-oral
      distraction device made of stainless steel and were scheduled for orthodontic
      treatment with bilateral first premolar extraction and then subsequent bilateral
      canine teeth distalization. RESULTS: In all the patients the canine teeth moved
      distally and made contact with the second premolars within 14-16 days range after
      which they were kept passive, with the appliance for a week of consolidation. The
      amount of canine retraction was in 7-7.5mms range, in all the patients, in each
      of the four quadrants studied. Bodily movement, tipping and buccal flaring of the
      canine teeth were noticed in all the cases. CONCLUSION: Combination of newer
      orthodontic appliances and the principles of biomechanics to maintain the control
      over rapid tooth movement, rapid canine distalization using distraction
      osteogenesis awaits further development before routine application, of this
      innovative and exciting approach. How to cite the article: Nair A, Kumar JP,
      Venkataramana V, Yuvaraj A, Reddy VS, Kumar SK. Dento-Alveolar distraction
      osteogenesis using rigid intra-oral tooth borne distraction device. J Int Oral
      Health 2014;6(2):106-13.

PMID- 24876712
TI  - The Clinical, Radiographic and Histological evaluation of three different
      concentrations of Formocresol as a pulpotomy agent.
AB  - BACKGROUND: Formocresol, though the center of much controversy is still the most
      widely used medicament for primary teeth pulpotomy and an intracanal medicament
      which has undergone a lengthy evolution to shorten the formocresol application
      time and reduce the concentration of formocresol exposure to the pulp tissue.
      Hence, the determination of the actual effective dose and concentration of
      formocresol for clinical application in primary teeth is an important area of
      research and a thorough clinical, radiographic and histological investigation in
      human subjects is very much needed. MATERIALS & METHODS: The study was conducted
      on 45 primary molars for the Clinical, Radiographic study and 45 premolars
      orthodontically indicated for extraction for the Histological study. The samples
      were randomly and equally divided into 3 groups of 15 each for pulpotomy with
      full strength formocresol, 1:5 diluted formocresol and 1:25 diluted formocresol
      respectively. The pulpotomized primary molars were clinically evaluated at 1st,
      3rd, 6th and 9th month while the pulpotomized premolars were subjected for
      histological evaluation after extraction. RESULTS: Obtained by chi-square test
      revealed that all the pulpotomized primary molars were asymptomatic till the end
      of the study period; suggesting 100% clinical and radiographic success while
      histologically, the three concentrations of formocresol showed decreased severity
      of fixation of the pulp tissue with decreasing concentration of formocresol.
      CONCLUSION: It can be inferred that the diluted formulations (1:5 and 1:25) of
      formocresol are equally efficient when compared to full-strength formocresol and
      thus, can be recommended for pulpotomy in primary teeth. How to cite the article:
      Goyal S, Abuwala T, Joshi K, Mehta J, Indushekar KR, Hallikerimath S. The
      Clinical, Radiographic and Histological evaluation of three different
      concentrations of Formocresol as a pulpotomy agent. J Int Oral Health
      2014;6(2):118-25.

PMID- 24876713
TI  - Assessment of oral side effects of Antiepileptic drugs and traumatic oro-facial
      injuries encountered in Epileptic children.
AB  - BACKGROUND: Epilepsy is a chronic disorder with unpredictably recurring seizure.
      Uncontrolled attacks can put patients at risk of suffering oro-facial trauma.
      Antiepileptic drugs (AED) provide satisfactory control of seizures in most of the
      patients with epilepsy. However use of AED has been found to cause many side
      effects inclusive of side effects in the oral cavity also. MATERIALS & METHODS:
      This study was conducted on 150 epileptic children, who were on anti epileptic
      medication for one year. RESULTS: Gingival over growth was seen as common side
      effect of the AED drugs. Lip and cheek biting were the most common soft tissue
      injury, while tooth fracture was the most common hard tissue dental injury.
      CONCLUSION: General physicians, physicians & dentists should be well aware of the
      potential side effects of AED. A Dentist should be well versed and trained to
      manage oro-facial injuries in the emergency department. How to cite the article:
      Ghafoor PA, Rafeeq M, Dubey A. Assessment of oral side effects of Antiepileptic
      drugs and traumaticoro-facial injuries encountered in Epileptic children. J Int
      Oral Health 2014;6(2):126-8.

PMID- 24876714
TI  - A case report of a rare finding of supernumerary primary and permanent canines.
AB  - A supernumerary tooth is a tooth that is additional to the normal series of
      teeth. These can occur anywhere in the primary or permanent dentition and are
      most commonly found in the anterior maxilla. Supernumerary canines are rare with
      little available literature and case reports in this area. This case presents a
      patient with a unilateral maxillary supernumerary deciduous and permanent canine
      associated with an unusual cleft of the alveolus. How to cite the article: Parker
      K, Hay N. A case report of a rare finding of supernumerary primary and permanent
      canines. J Int Oral Health 2014;6(2):129-131. 

PMID- 24876715
TI  - Predictable aesthetic outcome with immediate placement and early loading of one
      piece mini implant - A 5 year follow-up case report.
AB  - One piece mini implants are viable and predictable options to conventional
      implants in areas of deficit bone width. These can be placed without complex
      surgical augmentation procedures and are cost effective. Four mini implants were
      placed in a 40 year old female patient replacing her mobile mandibular anterior
      teeth. Provisional restoration was given after 2 weeks followed by individual
      ceramic crowns after 6 months. 5 year follow-up showed aesthetic soft tissue
      contours and successful osseointegration. One piece mini implants are viable
      treatment option in the aesthetic management of partial edentulism especially in
      the mandibular anterior region. How to cite the article: Mohan CS, Harinath P,
      Cholan PK, Kumar DL . Predictable aesthetic outcome with immediate placement and
      early loading of one piece mini implant - A 5 year follow-up case report. J Int
      Oral Health 2014;6(2):132-5. 

PMID- 24876716
TI  - A multidisciplinary approach to full mouth rehabilitation and solving the dilemma
      of wriggling dentures- a case report.
AB  - A successful management of full mouth rehabilitation demands a multi-disciplinary
      approach for its long lasting success. The present case report is intended to
      give an insight into the use of multiple treatment modalities to achieve a
      balanced, efficient and biomechanically successful prosthodontic treatment with
      acceptable aesthetics. Treatment of a maxillary and mandibular bilateral distal
      free end edentulous arch along with upper and lower anterior teeth requires
      plenty of contemporary and conventional prosthodontic treatment modalities.
      Management of distal extension situation provides complexity of biomechanical
      problems due to the three dimensional movements of the distal extension denture.
      A distal most implant can convert a distal extension RPD from a tooth and tissue
      supported prosthesis to a tooth and implant supported prosthesis which provides a
      definite stop thus enhancing the retention and stability of the prosthesis,
      eliminating the problems often associated with a tooth and tissue supported
      distal extension RPD. How to cite the article: Nidawani P, Galagali G, Reddy ES,
      Behera SS. A Multidisciplinary Approach to Full Mouth Rehabilitation and Solving
      the Dilemma of Wriggling Dentures- A Case Report. J Int Oral Health 2014;6(2):136
      40. 

PMID- 24876717
TI  - Prognostic factors for hepatocellular carcinoma recurrence.
AB  - The recurrence of hepatocellular carcinoma, the sixth most common neoplasm and
      the third leading cause of cancer-related mortality worldwide, represents an
      important clinical problem, since it may occur after both surgical and medical
      treatment. The recurrence rate involves 2 phases: an early phase and a late
      phase. The early phase usually occurs within 2 years after resection; it is
      mainly related to local invasion and intrahepatic metastases and, therefore, to
      the intrinsic biology of the tumor. On the other hand, the late phase occurs more
      than 2 years after surgery and is mainly related to de novo tumor formation as a
      consequence of the carcinogenic cirrhotic environment. Since recent studies have
      reported that early and late recurrences may have different risk factors, it is
      clinically important to recognize these factors in the individual patient as soon
      as possible. The aim of this review was, therefore, to identify predicting
      factors for the recurrence of hepatocellular carcinoma, by means of invasive and
      non-invasive methods, according to the different therapeutic strategies
      available. In particular the role of emerging techniques (e.g., transient
      elastography) and biological features of hepatocellular carcinoma in predicting
      recurrence have been discussed. In particular, invasive methods were
      differentiated from non-invasive ones for research purposes, taking into
      consideration the emerging role of the genetic signature of hepatocellular
      carcinoma in order to better allocate treatment strategies and surveillance
      follow-up in patients with this type of tumor.

PMID- 24876718
TI  - Occult hepatitis B virus and hepatocellular carcinoma.
AB  - Occult hepatitis B virus (HBV) infection (OBI) is a challenging pathobiological
      and clinical issue that has been widely debated for several decades. By
      definition, OBI is characterized by the persistence of HBV DNA in the liver
      tissue (and in some cases also in the serum) in the absence of circulating HBV
      surface antigen (HBsAg). Many epidemiological and molecular studies have
      indicated that OBI is an important risk factor for hepatocellular carcinoma (HCC)
      development. OBI may exert direct pro-oncogenic effects through the activation of
      the same oncogenic mechanisms that are activated in the course of an HBsAg
      positive infection. Indeed, in OBI as in HBV-positive infection, HBV DNA can
      persist in the hepatocytes both integrated into the host genome as well as free
      episome, and may maintain the capacity to produce proteins-mainly X protein and
      truncated preS-S protein - provided with potential transforming properties.
      Furthermore, OBI may indirectly favor HCC development. It has been shown that the
      persistence of very low viral replicative activity during OBI may induce mild
      liver necro-inflammation continuing for life, and substantial clinical evidence
      indicates that OBI can accelerate the progression of liver disease towards
      cirrhosis that is considered the most important risk factor for HCC development.

PMID- 24876719
TI  - miR-106b-25/miR-17-92 clusters: polycistrons with oncogenic roles in
      hepatocellular carcinoma.
AB  - MicroRNAs are small endogenously expressed RNA molecules which are involved in
      the process of silencing gene expression through translational regulation. The
      polycistronic miR-17-92 cluster is the first microRNA cluster shown to play a
      role in tumorigenesis. It has two other paralogs in the human genome, the miR
      106b-25 cluster and the miR-106a-363 cluster. Collectively, the microRNAs encoded
      by these clusters can be further grouped based on the seed sequences into four
      families, namely the miR-17, the miR-92, the miR-18 and the miR-19 families. Over
      expression of the miR-106b-25 and miR-17-92 clusters has been reported not only
      during the development of cirrhosis but also subsequently during the development
      of hepatocellular carcinoma. Members of these clusters have also been shown to
      affect the replication of hepatitis B and hepatitis C viruses. Various targets of
      these microRNAs have been identified, and these targets are involved in tumor
      growth, cell survival and metastasis. In this review, we first describe the
      regulation of these clusters by c-Myc and E2F1, and how the members of these
      clusters in turn regulate E2F1 expression forming an auto-regulatory loop. In
      addition, the roles of the various members of the clusters in affecting relevant
      target gene expression in the pathogenesis of hepatocellular carcinoma will also
      be discussed.

PMID- 24876722
TI  - Significance of viral status on occurrence of hepatitis B-related hepatocellular
      carcinoma.
AB  - Hepatitis B virus (HBV) infection remains a challenging global health problem,
      with more than 350 million people chronically infected and at risk of developing
      hepatocellular carcinoma (HCC). Interactions that occur among host,
      environmental, and viral factors determine the natural course and predict the
      prognosis of patients with chronic HBV infection. In the past decades, several
      important viral factors of predictive of HCC have been identified, such as high
      hepatitis B surface antigen level, seropositivity of hepatitis B e antigen, high
      viral load, viral genotype, and specific viral sequence mutations. Identification
      of certain viral risk factors for HCC development and stratification of patient
      risk are very important to perform future surveillance programs. In this article,
      we thus reviewed the risk of viral factors involved in hepatocarcinogenesis.

PMID- 24876721
TI  - Value of radiofrequency ablation in the treatment of hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is a malignant disease that substantially affects
      public health worldwide. It is especially prevalent in east Asia and sub-Saharan
      Africa, where the main etiology is the endemic status of chronic hepatitis B.
      Effective treatments with curative intent for early HCC include liver
      transplantation, liver resection (LR), and radiofrequency ablation (RFA). RFA has
      become the most widely used local thermal ablation method in recent years because
      of its technical ease, safety, satisfactory local tumor control, and minimally
      invasive nature. This technique has also emerged as an important treatment
      strategy for HCC in recent years. RFA, liver transplantation, and hepatectomy can
      be complementary to one another in the treatment of HCC, and the outcome benefits
      have been demonstrated by numerous clinical studies. As a pretransplantation
      bridge therapy, RFA extends the average waiting time without increasing the risk
      of dropout or death. In contrast to LR, RFA causes almost no intra-abdominal
      adhesion, thus producing favorable conditions for subsequent liver
      transplantation. Many studies have demonstrated mutual interactions between RFA
      and hepatectomy, effectively expanding the operative indications for patients
      with HCC and enhancing the efficacy of these approaches. However, treated tumor
      tissue remains within the body after RFA, and residual tumors or satellite
      nodules can limit the effectiveness of this treatment. Therefore, future research
      should focus on this issue.

PMID- 24876720
TI  - MicroRNAs as therapeutic strategy for hepatitis B virus-associated hepatocellular
      carcinoma: current status and future prospects.
AB  - Hepatocellular carcinoma (HCC) remains to be one of the top causing cancer
      related deaths today. The majority of HCC cases are reported to be the result of
      chronic hepatitis B virus (HBV) infection. Current treatments for HBV-related HCC
      revolve around the use of drugs to inhibit viral replication, as a high level of
      viral load and antigen in circulation often presents a poor patient prognosis.
      However, existing therapies are inefficient in the complete eradication of HBV,
      often resulting in tumour recurrence. The involvement of microRNAs (miRNAs) in
      important processes in HBV-related HCC makes it an important player in the
      progression of HCC in chronic hepatitis B infected patients. In this review, we
      discuss the key aspects of HBV infection and the important viral products that
      may regulate cancer-related processes via their interaction with miRNAs or their
      closely related protein machinery. Conversely, we also look at how miRNAs may go
      about regulating the virus, especially in vital processes like viral replication.
      Apart from miRNAs acting as either oncogenes or tumour-suppressors, we also look
      at how miRNAs may function as biomarkers that may possibly serve as better
      candidates than those currently employed in the diagnosis of HBV infection or HBV
      related HCC. A summary of the roles of miRNAs in HBV-related HCC will hopefully
      lead to a gain in understanding of the pathogenesis process and pave the way for
      new insights in medical therapy.

PMID- 24876723
TI  - Impact of antiviral therapy on post-hepatectomy outcome for hepatitis B-related
      hepatocellular carcinoma.
AB  - The outcome after curative resection for hepatocellular carcinoma (HCC) remains
      unsatisfactory due to the high recurrence rate after surgery. In patients with
      hepatitis B virus (HBV)-related HCC, which is the majority of patients with HCC
      in Asia, a high viral load is a strong risk factor for HCC recurrence. It is
      logical to believe that antiviral therapy may improve the post-operative outcome
      by promoting viral clearance and hepatocyte regeneration, as well as improving
      residual liver volume in HCC patients with hepatitis B. However, the effect of
      antiviral therapy on clinical outcomes after liver resection in patients with HBV
      related HCC remains to be established. There are two main groups of antiviral
      treatment for HBV-oral nucleos(t)ide analogues and interferon. Interferon
      treatment reduces the overall incidence of HBV-related HCC in sustained
      responders. However, side effects may limit its long-term clinical application.
      Nucleos(t)ide analogues carry fewer side effects and are potent in terms of viral
      suppression when compared to interferon and are typically implemented for
      patients with more advanced liver diseases. They may also improve the outcome
      after curative resection for HBV-related HCC. There are increasing evidence to
      suggest that antiviral therapy could suppress HBV, decrease the perioperative
      reactivation of viral replication, reduce liver injury, preserve the liver
      function before and after operation, and may lower the risk of HCC recurrence.
      After all, antiviral therapy may improve the survival after liver resection by
      reducing recurrence and delaying the liver damage by the virus, resulting in a
      higher chance of receiving aggressive salvage therapy during HCC recurrence.

PMID- 24876724
TI  - Irritable bowel syndrome in children: pathogenesis, diagnosis and evidence-based
      treatment.
AB  - Irritable bowel syndrome (IBS) is the commonest cause of recurrent abdominal pain
      (RAP) in children in both more developed and developing parts of the world. It is
      defined by the Rome III criteria for functional gastrointestinal disorders. It is
      characterized by abdominal pain that is improved by defecation and whose onset is
      associated with a change in stool form and or frequency and is not explained by
      structural or biochemical abnormalities. It is estimated that 10%-15% of older
      children and adolescents suffer from IBS. IBS can be considered to be a brain-gut
      disorder possibly due to complex interaction between environmental and hereditary
      factors. The diagnosis of IBS is made based on the Rome III criteria together
      with ruling out organic causes of RAP in children such as inflammatory bowel
      disease and celiac disease. Once the diagnosis of IBS is made, it is important to
      explain to the parents (and children) that there is no serious underlying
      disease. This reassurance may be effective treatment in a large number of cases.
      Lifestyle modifications, stress management, dietary interventions and probiotics
      may be beneficial in some cases. Although there is limited evidence for efficacy
      of pharmacological therapies such as antispasmodics and antidiarrheals; these
      have a role in severe cases. Biopsychosocial therapies have shown encouraging
      results in initial trials but are beset by limited availability. Further research
      is necessary to understand the pathophysiology and provide specific focused
      therapies.

PMID- 24876725
TI  - Irritable bowel syndrome: relations with functional, mental, and somatoform
      disorders.
AB  - This review describes the conceptual and clinical relations between irritable
      bowel syndrome (IBS), other functional, somatoform, and mental disorders, and
      points to appropriate future conceptualizations. IBS is considered to be a
      functional somatic syndrome (FSS) with a considerable symptom overlap with other
      FSSs like chronic fatigue syndrome or fibromyalgia syndrome. IBS patients show an
      increased prevalence of psychiatric symptoms and disorders, especially depression
      and anxiety. IBS is largely congruent with the concepts of somatoform and somatic
      symptom disorders. Roughly 50% of IBS patients complain of gastrointestinal
      symptoms only and have no psychiatric comorbidity. IBS concepts, treatment
      approaches, as well as health care structures should acknowledge its variability
      and multidimensionality by: (1) awareness of additional extraintestinal and
      psychobehavioral symptoms in patients with IBS; (2) general and collaborative
      care rather than specialist and separated care; and (3) implementation of
      "interface disorders" to abandon the dualistic classification of purely organic
      or purely mental disorders.

PMID- 24876726
TI  - Role of antispasmodics in the treatment of irritable bowel syndrome.
AB  - Irritable bowel syndrome (IBS) is a long-lasting, relapsing disorder
      characterized by abdominal pain/discomfort and altered bowel habits. Intestinal
      motility impairment and visceral hypersensitivity are the key factors among its
      multifactorial pathogenesis, both of which require effective treatment. Voltage
      gated calcium channels mediate smooth muscle contraction and endocrine secretion
      and play important roles in neuronal transmission. Antispasmodics are a group of
      drugs that have been used in the treatment of IBS for decades. Alverine citrate,
      a spasmolytic, decreases the sensitivity of smooth muscle contractile proteins to
      calcium, and it is a selective 5-HT1A receptor antagonist. Alverine, in
      combination with simethicone, has been demonstrated to effectively reduce
      abdominal pain and discomfort in a large placebo-controlled trial. Mebeverine is
      a musculotropic agent that potently blocks intestinal peristalsis. Non-placebo
      controlled trials have shown positive effects of mebeverine in IBS regarding
      symptom control; nevertheless, in recent placebo-controlled studies, mebeverine
      did not exhibit superiority over placebo. Otilonium bromide is poorly absorbed
      from the GI tract, where it acts locally as an L-type calcium channel blocker, an
      antimuscarinic and a tachykinin NK2 receptor antagonist. Otilonium has
      effectively reduced pain and improved defecation alterations in placebo
      controlled trials in IBS patients. Pinaverium bromide is also an L-type calcium
      channel blocker that acts locally in the GI tract. Pinaverium improves motility
      disorders and consequently reduces stool problems in IBS patients. Phloroglucinol
      and trimethylphloroglucinol are non-specific antispasmodics that reduced pain in
      IBS patients in a placebo-controlled trial. Antispasmodics have excellent safety
      profiles. T-type calcium channel blockers can abolish visceral hypersensitivity
      in animal models, which makes them potential candidates for the development of
      novel therapeutic agents in the treatment of IBS.

PMID- 24876727
TI  - Acupuncture-moxibustion in treating irritable bowel syndrome: how does it work?
AB  - Irritable bowel syndrome (IBS) is a functional intestinal disease characterized
      by abdominal pain or discomfort and altered bowel habits. It has drawn great
      attention because of its high prevalence, reoccurring symptoms, and severe
      influence on patients' lives. Many clinical studies have demonstrated the
      efficacy of acupuncture-moxibustion in treating IBS. Increasing attention has
      been paid to research regarding the action mechanisms of acupuncture-moxibustion
      for IBS, and the adoption of modern techniques has achieved some progress. This
      article reviews the latest advances among action mechanism studies from the
      perspectives of gastrointestinal motility, visceral hypersensitivity, the brain
      gut axis, the neuroendocrine system, and the immune system. It is shown that
      acupuncture-moxibustion can effectively regulate the above items, and thus, this
      treatment should have a high efficacy in the treatment of IBS. This article also
      identifies existing problems in current mechanism research and raises several
      ideas for future studies. Further revelations regarding these action mechanisms
      will promote the application of acupuncture-moxibustion in treating IBS. 

PMID- 24876729
TI  - Single-incision laparoscopic colorectal surgery for cancer: state of art.
AB  - A number of clinical trials have demonstrated that the laparoscopic approach for
      colorectal cancer resection provides the same oncologic results as open surgery
      along with all clinical benefits of minimally invasive surgery. During the last
      years, a great effort has been made to research for minimizing parietal trauma,
      yet for cosmetic reasons and in order to further reduce surgery-related pain and
      morbidity. New techniques, such as natural orifice transluminal endoscopic
      surgery (NOTES) and single-incision laparoscopy (SIL) have been developed in
      order to reach the goal of "scarless" surgery. Although NOTES may seem not fully
      suitable or safe for advanced procedures, such as colectomies, SIL is currently
      regarded as the next major advance in the progress of minimally invasive surgical
      approaches to colorectal disease that is more feasible in generalized use. The
      small incision through the umbilicus allows surgeons to use familiar standard
      laparoscopic instruments and thus, perform even complex procedures which require
      extraction of large surgical specimens or intestinal anastomosis. The cosmetic
      result from SIL is also better because the only incision is made through the
      umbilicus which can hide the wound effectively after operation. However, SIL
      raises a number of specific new challenges compared with the laparoscopic
      conventional approach. A reduced capacity for triangulation, the repeated
      conflicts between the shafts of the instruments and the difficulties to achieve a
      correct exposure of the operative field are the most claimed issues. The use
      therefore of this new approach for complex colorectal procedures might
      understandingly be viewed as difficult to implement, especially for oncologic
      cases.

PMID- 24876730
TI  - Bevacizumab in the pre-operative treatment of locally advanced rectal cancer: a
      systematic review.
AB  - Despite advances in the management of patients with locally advanced, non
      metastatic rectal adenocarcinoma (LARC), prognosis remains largely unsatisfactory
      due to a high rate of distant relapse. In fact, currently available neoadjuvant
      protocols, represented by fluoropyrimidine-based chemo-radiotherapy (CT-RT) or
      short-course RT, together with improved surgical techniques, have largely reduced
      the risk of local relapse, with limited impact on distant recurrence. Available
      results of phase III trials with additional cytotoxic agents combined with
      standard CT-RT are disappointing, as no significant reduction in the risk of
      recurrence has been demonstrated. In order to improve the control of
      micrometastatic disease, integrating targeted agents into neoadjuvant treatment
      protocols thus offers a rational approach. In particular, the antiangiogenic
      agent bevacizumab has demonstrated synergistic activity with both CT and RT in
      pre-clinical and clinical models, and thus may represent a suitable companion in
      the neoadjuvant treatment of LARC. Preliminary results of phase I-II clinical
      studies are promising and suggest potential clinical parameters and molecular
      predictive biomarkers useful for patient selection: treatment personalization is
      indeed the key in order to maximize the benefit while reducing the risk of more
      complex neoadjuvant treatment schedules.

PMID- 24876731
TI  - Should capecitabine replace 5-fluorouracil in the first-line treatment of
      metastatic colorectal cancer?
AB  - Fluoropyrimidines play a central role in the first-line treatment of metastatic
      colorectal cancer. Our aim was to review whether capecitabine was a safer, non
      inferior, economically superior and more convenient alternative to 5
      fluorouracil. Capecitabine has previously been compared to 5-fluorouracil-either
      as a monotherapy or in combination with oxaliplatin, irinotecan, or biological
      drugs-and has been found to have comparable efficacy and safety profiles.
      Furthermore, pharmacoeconomic data and patients' preferences for oral
      chemotherapy further favor capecitabine. Therefore, capecitabine appears to be an
      effective and safe alternative to fluorouracil in the first-line treatment of
      metastatic colorectal cancer.

PMID- 24876728
TI  - Epidemiological transition of colorectal cancer in developing countries:
      environmental factors, molecular pathways, and opportunities for prevention.
AB  - Colorectal cancer (CRC) is one of the leading causes of cancer and cancer-related
      mortality worldwide. The disease has been traditionally a major health problem in
      industrial countries, however the CRC rates are increasing in the developing
      countries that are undergoing economic growth. Several environmental risk
      factors, mainly changes in diet and life style, have been suggested to underlie
      the rise of CRC in these populations. Diet and lifestyle impinge on nuclear
      receptors, on the intestinal microbiota and on crucial molecular pathways that
      are implicated in intestinal carcinogenesis. In this respect, the epidemiological
      transition in several regions of the world offers a unique opportunity to better
      understand CRC carcinogenesis by studying the disease phenotypes and their
      environmental and molecular associations in different populations. The data from
      these studies may have important implications for the global prevention and
      treatment of CRC.

PMID- 24876732
TI  - Targeted therapy in advanced metastatic colorectal cancer: current concepts and
      perspectives.
AB  - The introduction of new cytotoxic substances as well as agents that target
      vascular endothelial growth factor (VEGF) and epidermal growth factor receptor
      (EGFR) signaling has improved clinical outcome of patients with metastatic
      colorectal cancer (mCRC). In this review we summarize the most relevant clinical
      data on VEGF and EGFR targeting regimens in mCRC. The effects of available
      treatment strategies for mCRC are often temporary, with resistance and disease
      progression developing in most patients. Thus, new treatment strategies are
      urgently needed. Some GI peptides including gastrin and gastrin releasing
      peptide, certain growth factors such as insulin-like growth factor-I and II and
      neuropeptides such as growth hormone releasing hormone (GHRH) are implicated in
      the growth of CRC. Experimental investigations in CRC with antagonistic analogs
      of bombesin/gastrin-releasing peptide, GHRH, and with cytotoxic peptides that can
      be targeted to peptide receptors on tumors, are summarized in the second part of
      the review.

PMID- 24876733
TI  - Role of surgery in colorectal cancer liver metastases.
AB  - Colorectal carcinoma (CRC) is the third most common cancer, and approximately 35%
      55% of patients with CRC will develop hepatic metastases during the course of
      their disease. Surgical resection represents the only chance of long-term
      survival. The goal of surgery should be to resect all metastases with negative
      histological margins while preserving sufficient functional hepatic parenchyma.
      Although resection remains the only chance of long-term survival, management
      strategies should be tailored for each case. For patients with extensive
      metastatic disease who would otherwise be unresectable, the combination of
      advances in medical therapy, such as systemic chemotherapy (CTX), and the
      improvement in surgical techniques for metastatic disease, have enhanced
      prognosis with prolongation of the median survival rate and cure. The use of
      portal vein embolization and preoperative CTX may also increase the number of
      patients suitable for surgical treatment. Despite current treatment options, many
      patients still experience a recurrence after hepatic resection. More active
      systemic CTX agents are being used increasingly as adjuvant therapy either before
      or after surgery. Local tumor ablative therapies, such as microwave coagulation
      therapy and radiofrequency ablation therapy, should be considered as an adjunct
      to hepatic resection, in which resection cannot deal with all of the tumor
      lesions. Formulation of an individualized plan, which combines surgery with
      systemic CTX, is a necessary task of the multidisciplinary team. The aim of this
      paper is to discuss different approaches for patients that are treated due to CRC
      liver metastasis.

PMID- 24876734
TI  - Clinicopathological utility of sialoglycoconjugates in diagnosing and treating
      colorectal cancer.
AB  - Aberrant expression of glycoconjugates occurs during malignant transformation of
      cancer cells. Overexpression of sialoglycoconjugates in particular may play an
      important role in the progression, i.e., invasion or metastasis, of cancer.
      Various types of sialoglycoconjugates have been investigated to clarify their
      biological significance and clinical utility in diagnosing and treating
      colorectal cancer. This review focuses specifically on expression of mucin (MUC)
      1 and it suggests that MUC1 with the specific structure of a sialo
      oligosaccharide has biological significance in determining the metastatic
      potential of colorectal cancer cells and clinicopathological utility in
      evaluating the effectiveness of treatments and the prognosis for patients with
      colorectal cancer. Further studies are expected to contribute to the expanded use
      of cancer-associated sialoglycoconjugates in cancer diagnosis and therapy.

PMID- 24876735
TI  - Pulmonary metastasectomy for colorectal cancer: how many nodules, how many times?
AB  - Colorectal cancer (CRC) is one of the most common cancers worldwide, with 5%-15%
      of CRC patients eventually developing lung metastasis (LM). Despite doubts about
      the role of locoregional therapy in the management of systemic disease, many
      surgeons have performed pulmonary metastasectomy (PM) for CRC in properly
      selected patients. However, the use of pulmonary metastasectomy remains
      controversial due to the lack of randomized controlled studies. This article
      reviews the results of surgical treatment of pulmonary metastases for CRC,
      focusing on (1) current treatment guidelines and surgical techniques of PM in
      patients with LM from CRC; (2) outcomes of PM and its prognostic factors; and (3)
      controversial issues in PM, focusing on repeated metastasectomy, bilateral
      multiple metastases, and combined liver and lung metastasectomy.

PMID- 24876736
TI  - Transfusion and coagulation management in liver transplantation.
AB  - There is wide variation in the management of coagulation and blood transfusion
      practice in liver transplantation. The use of blood products intraoperatively is
      declining and transfusion free transplantations take place ever more frequently.
      Allogenic blood products have been shown to increase morbidity and mortality.
      Primary haemostasis, coagulation and fibrinolysis are altered by liver disease.
      This, combined with intraoperative disturbances of coagulation, increases the
      risk of bleeding. Meanwhile, the rebalancing of coagulation homeostasis can put
      patients at risk of hypercoagulability and thrombosis. The application of the
      principles of patient blood management to transplantation can reduce the risk of
      transfusion. This includes: preoperative recognition and treatment of anaemia,
      reduction of perioperative blood loss and the use of restrictive haemoglobin
      based transfusion triggers. The use of point of care coagulation monitoring using
      whole blood viscoelastic testing provides a picture of the complete coagulation
      process by which to guide and direct coagulation management. Pharmacological
      methods to reduce blood loss include the use of anti-fibrinolytic drugs to reduce
      fibrinolysis, and rarely, the use of recombinant factor VIIa. Factor concentrates
      are increasingly used; fibrinogen concentrates to improve clot strength and
      stability, and prothrombin complex concentrates to improve thrombin generation.
      Non-pharmacological methods to reduce blood loss include surgical utilisation of
      the piggyback technique and maintenance of a low central venous pressure. The use
      of intraoperative cell salvage and normovolaemic haemodilution reduces allogenic
      blood transfusion. Further research into methods of decreasing blood loss and
      alternatives to blood transfusion remains necessary to continue to improve
      outcomes after transplantation.

PMID- 24876738
TI  - Donor transmitted and de novo cancer after liver transplantation.
AB  - Cancers in solid organ recipients may be classified as donor transmitted, donor
      derived, de novo or recurrent. The risk of donor-transmitted cancer is very low
      and can be reduced by careful screening of the donor but cannot be abolished and,
      in the United Kingdom series is less than 0.03%. For donors with a known history
      of cancer, the risks will depend on the nature of the cancer, the interventions
      given and the interval between diagnosis and organ donation. The risks of cancer
      transmission must be balanced against the risks of death awaiting a new graft and
      strict adherence to current guidelines may result increased patient death. Organs
      from selected patients, even with high-grade central nervous system (CNS)
      malignancy and after a shunt, can, in some circumstances, be considered. Of
      potential donors with non-CNS cancers, whether organs may be safely used again
      depends on the nature of the cancer, the treatment and interval. Data are scarce
      about the most appropriate treatment when donor transmitted cancer is diagnosed:
      sometimes substitution of agents and reduction of the immunosuppressive load may
      be adequate and the impact of graft removal should be considered but not always
      indicated. Liver allograft recipients are at increased risk of some de novo
      cancers, especially those grafted for alcohol-related liver disease and hepatitis
      C virus infection. The risk of lymphoproliferative disease and cancers of the
      skin, upper airway and bowel are increased but not breast. Recipients should be
      advised to avoid risk behavior and monitored appropriately.

PMID- 24876737
TI  - Aetiology and risk factors of ischaemic cholangiopathy after liver
      transplantation.
AB  - Liver transplantation (LT) is the best treatment for end-stage hepatic failure,
      with an excellent survival rates over the last decade. Biliary complications
      after LT pose a major challenge especially with the increasing number of procured
      organs after circulatory death. Ischaemic cholangiopathy (IC) is a set of
      disorders characterized by multiple diffuse strictures affecting the graft
      biliary system in the absence of hepatic artery thrombosis or stenosis. It
      commonly presents with cholestasis and cholangitis resulting in higher
      readmission rates, longer length of stay, repeated therapeutic interventions, and
      eventually re-transplantation with consequent effects on the patient's quality of
      life and increased health care costs. The pathogenesis of IC is unclear and
      exhibits a higher prevalence with prolonged ischaemia time, donation after
      circulatory death (DCD), rejection, and cytomegalovirus infection. The majority
      of IC occurs within 12 mo after LT. Prolonged warm ischaemic times predispose to
      a profound injury with a subsequently higher prevalence of IC. Biliary
      complications and IC rates are between 16% and 29% in DCD grafts compared to
      between 3% and 17% in donation after brain death (DBD) grafts. The majority of
      ischaemic biliary lesions occur within 30 d in DCD compared to 90 d in DBD grafts
      following transplantation. However, there are many other risk factors for IC that
      should be considered. The benefits of DCD in expanding the donor pool are
      hindered by the higher incidence of IC with increased rates of re
      transplantation. Careful donor selection and procurement might help to optimize
      the utilization of DCD grafts.

PMID- 24876739
TI  - Post-operative imaging in liver transplantation: state-of-the-art and future
      perspectives.
AB  - Orthotopic liver transplantation (OLT) represents a major treatment for end-stage
      chronic liver disease, as well as selected cases of hepatocellular carcinoma and
      acute liver failure. The ever-increasing development of imaging modalities
      significantly contributed, over the last decades, to the management of recipients
      both in the pre-operative and post-operative period, thus impacting on graft and
      patients survival. When properly used, imaging modalities such as ultrasound,
      multidetector computed tomography, magnetic resonance imaging (MRI) and
      procedures of direct cholangiography are capable to provide rapid and reliable
      recognition and treatment of vascular and biliary complications occurring after
      OLT. Less defined is the role for imaging in assessing primary graft dysfunction
      (including rejection) or chronic allograft disease after OLT, e.g., hepatitis C
      virus (HCV) recurrence. This paper: (1) describes specific characteristic of the
      above imaging modalities and the rationale for their use in clinical practice;
      (2) illustrates main imaging findings related to post-OLT complications in adult
      patients; and (3) reviews future perspectives emerging in the surveillance of
      recipients with HCV recurrence, with special emphasis on MRI.

PMID- 24876740
TI  - Multidrug-resistant bacterial infections after liver transplantation: an ever
      growing challenge.
AB  - Bacterial infections are a leading cause of morbidity and mortality among solid
      organ transplant recipients. Over the last two decades, various multidrug
      resistant (MDR) pathogens have emerged as relevant causes of infection in this
      population. Although this fact reflects the spread of MDR pathogens in health
      care facilities worldwide, several factors relating to the care of transplant
      donor candidates and recipients render these patients particularly prone to the
      acquisition of MDR bacteria and increase the likelihood of MDR infectious
      outbreaks in transplant units. The awareness of this high vulnerability of
      transplant recipients to infection leads to the more frequent use of broad
      spectrum empiric antibiotic therapy, which further contributes to the selection
      of drug resistance. This vicious cycle is difficult to avoid and leads to a
      scenario of increased complexity and narrowed therapeutic options. Infection by
      MDR pathogens is more frequently associated with a failure to start appropriate
      empiric antimicrobial therapy. The lack of appropriate treatment may contribute
      to the high mortality occurring in transplant recipients with MDR infections.
      Furthermore, high therapeutic failure rates have been observed in patients
      infected with extensively-resistant pathogens, such as carbapenem-resistant
      Enterobacteriaceae, for which optimal treatment remains undefined. In such a
      context, the careful implementation of preventive strategies is of utmost
      importance to minimize the negative impact that MDR infections may have on the
      outcome of liver transplant recipients. This article reviews the current
      literature regarding the incidence and outcome of MDR infections in liver
      transplant recipients, and summarizes current preventive and therapeutic
      recommendations.

PMID- 24876741
TI  - Bacterial infection after liver transplantation.
AB  - Infectious complications are major causes of morbidity and mortality after liver
      transplantation, despite recent advances in the transplant field. Bacteria,
      fungi, viruses and parasites can cause infection before and after
      transplantation. Among them, bacterial infections are predominant during the
      first two months post-transplantation and affect patient and graft survival. They
      might cause surgical site infections, including deep intra-abdominal infections,
      bacteremia, pneumonia, catheter-related infections and urinary tract infections.
      The risk factors for bacterial infections differ between the periods after
      transplant, and between centers. Recently, the emergence of multi-drug resistant
      bacteria is great concern in liver transplant (LT) patients. The instructive data
      about effects of infections with extended-spectrum beta lactamase producing
      bacteria, carbapenem-resistant gram-negative bacteria, and glycopeptide-resistant
      gram-positive bacteria were reported on a center-by-center basis. To prevent post
      transplant bacterial infections, proper strategies need to be established based
      upon center-specific data and evidence from well-controlled studies. This article
      reviewed the recent epidemiological data, risk factors for each type of
      infections and important clinical issues in bacterial infection after LT.

PMID- 24876742
TI  - Interventional radiology in living donor liver transplant.
AB  - The shortage of deceased donor liver grafts led to the use of living donor liver
      transplant (LDLT). Patients who undergo LDLT have a higher risk of complications
      than those who undergo deceased donor liver transplantation (LT). Interventional
      radiology has acquired a key role in every LT program by treating the majority of
      vascular and non-vascular post-transplant complications, improving graft and
      patient survival and avoiding, in the majority of cases, surgical revision and/or
      re-transplant. The aim of this paper is to review indications, diagnostic
      modalities, technical considerations, achievements and potential complications of
      interventional radiology procedures after LDLT.

PMID- 24876744
TI  - Role of hepatitis B virus DNA integration in human hepatocarcinogenesis.
AB  - Liver cancer ranks sixth in cancer incidence, and is the third leading cause of
      cancer-related deaths worldwide. Hepatocellular carcinoma (HCC) is the most
      common type of liver cancer, which arises from hepatocytes and accounts for
      approximately 70%-85% of cases. Hepatitis B virus (HBV) frequently causes liver
      inflammation, hepatic damage and subsequent cirrhosis. Integrated viral DNA is
      found in 85%-90% of HBV-related HCCs. Its presence in tumors from non-cirrhotic
      livers of children or young adults further supports the role of viral DNA
      integration in hepatocarcinogenesis. Integration of subgenomic HBV DNA fragments
      into different locations within the host DNA is a significant feature of chronic
      HBV infection. Integration has two potential consequences: (1) the host genome
      becomes altered ("cis" effect); and (2) the HBV genome becomes altered ("trans"
      effect). The cis effect includes insertional mutagenesis, which can potentially
      disrupt host gene function or alter host gene regulation. Tumor progression is
      frequently associated with rearrangement and partial gain or loss of both viral
      and host sequences. However, the role of integrated HBV DNA in
      hepatocarcinogenesis remains controversial. Modern technology has provided a new
      paradigm to further our understanding of disease mechanisms. This review
      summarizes the role of HBV DNA integration in human carcinogenesis.

PMID- 24876745
TI  - Risk calculators for hepatocellular carcinoma in patients affected with chronic
      hepatitis B in Asia.
AB  - Risk calculators are widely used in many clinical fields, and integrate several
      important risk factors through the conversion of a risk function into a single
      measure of risk. Several studies have been carried out to create risk calculators
      for the prediction of hepatocellular carcinoma (HCC) in patients with chronic
      hepatitis B (CHB). Most of them were hospital-based, with limited sample sizes
      and insufficient external validation. These study groups collaborated to
      establish the REACH-B risk score, which incorporated five clinical variables to
      predict HCC risk. This risk score was then validated in international clinical
      cohorts. Evidence suggests that quantitative serum HBsAg level provides
      additional predictability of HCC, especially in patients with low levels of
      hepatitis B virus DNA. This novel marker was incorporated into a risk calculator
      and was internally validated. This tool will hopefully be externally validated in
      the near future. Risk calculators can be used to support clinical practice, and
      to establish preventive measures; several "off-label" extension usages have also
      been implemented. Albeit beneficial, several precautions and discussions should
      be noted in using the risk calculators. The future development of risk
      calculators for CHB patients can be extended by applying them to additional CHB
      related outcomes, and by incorporating emerging risk parameters.

PMID- 24876743
TI  - Relationship between cytokine gene polymorphisms and chronic hepatitis B virus
      infection.
AB  - Hepatitis B virus (HBV) infection is still a public health problem worldwide,
      being endemic in some parts of the world. It can lead to serious liver diseases
      such as chronic hepatitis, cirrhosis, and hepatocellular cancer. The differences
      in host immune response can be one of the reasons for the various clinical
      presentations of HBV infection. Polymorphisms of genes encoding the
      proinflammatory and antiinflammatory cytokines, which are responsible for
      regulation of the immune response, can affect the clinical presentation of the
      infection. Particularly, the polymorphisms of the genes encoding cytokines such
      as interleukin (IL)-1, IL-6, IL-8, IL-10, IL-18, IL-28B, interferon-gamma, tumor
      necrosis factor-alpha, tumor growth factor-beta1, and regulatory molecules like
      vitamin D receptor and chemokine receptor 5 can be responsible for different
      clinical presentations of HBV infections. The genomic information about cytokines
      and other mediators can be important for determining high-risk people for
      developing chronic hepatitis or hepatocellular cancer and may be used to plan
      treatment and preventive approaches for these people. In this review, the current
      knowledge in the literature on the association between cytokine/regulatory
      molecule gene polymorphisms and clinical course of chronic HBV infection is
      summarized, and the clinical implementations and future prospects regarding this
      knowledge are discussed.

PMID- 24876746
TI  - Molecular mechanisms of gender disparity in hepatitis B virus-associated
      hepatocellular carcinoma.
AB  - Chronic hepatitis B virus (HBV) infection is one of the most common causes of
      hepatocellular carcinoma (HCC), a malignant tumor with high mortality worldwide.
      One remarkable clinical feature of HBV-related HCC is that its incidence is
      higher in males and postmenopausal females compared to other females. Increasing
      evidence indicates that HBV-associated HCC may involve gender disparity and that
      it may be a type of hormone-responsive malignant tumor. Sex hormones, such as
      androgen and estrogen, have been shown to play very different roles in the
      progression of an HBV infection and in the development of HBV-related HCC.
      Through binding to their specific cellular receptors and affecting the
      corresponding signaling pathways, sex hormones can regulate the transactivation
      of HBx, cause the chronic release of inflammatory cytokines in the hepatocellular
      microenvironment, and participate in epigenetic and genetic alternations in
      hepatocytes. All of these functions may be related to the initiation and
      progression of HBV-associated HCC. A thorough investigation of the molecular
      mechanisms underlying the gender-related disparity in HBV-related HCC should
      provide a new perspective for better understanding its pathogenesis and exploring
      more effective methods for the prevention and treatment of this disease.

PMID- 24876747
TI  - Management of chronic hepatitis B infection: current treatment guidelines,
      challenges, and new developments.
AB  - Chronic hepatitis B (CHB) virus infection is a global public health problem,
      affecting more than 400 million people worldwide. The clinical spectrum is wide,
      ranging from a subclinical inactive carrier state, to progressive chronic
      hepatitis, cirrhosis, decompensation, and hepatocellular carcinoma. However,
      complications of hepatitis B virus (HBV)-related chronic liver disease may be
      reduced by viral suppression. Current international guidelines recommend first
      line treatment of CHB infection with pegylated interferon, entecavir, or
      tenofovir, but the optimal treatment for an individual patient is controversial.
      The indications for treatment are contentious, and increasing evidence suggests
      that HBV genotyping, as well as serial on-treatment measurements of hepatitis B
      surface antigen and HBV DNA kinetics should be used to predict antiviral
      treatment response. The likelihood of achieving a sustained virological response
      is also increased by extending treatment duration, and using combination therapy.
      Hence the paradigm for treatment of CHB is constantly evolving. This article
      summarizes the different indications for treatment, and systematically reviews
      the evidence for the efficacy of various antiviral agents. It further discusses
      the shortcomings of current guidelines, use of rescue therapy in drug-resistant
      strains of HBV, and highlights the promising clinical trials for emerging
      therapies in the pipeline. This concise overview presents an updated practical
      approach to guide the clinical management of CHB.

PMID- 24876749
TI  - Telomere and telomerase in chronic liver disease and hepatocarcinoma.
AB  - The pathogenesis of liver cirrhosis is not completely elucidated. Although in the
      majority of patients, the risk factors may be identified in B and C viral
      hepatitis, alcohol intake, drugs or fatty liver disease, there is a small
      percentage of patients with no apparent risk factors. In addition, the evolution
      of chronic liver disease is highly heterogeneous from one patient to another.
      Among patient with identical risk factors, some rapidly progress to cirrhosis and
      hepatocellular carcinoma (HCC) whereas others have a benign course. Therefore, a
      genetic predisposition may contribute to the development of cirrhosis and HCC.
      Evidence supporting the role of genetic factors as a risk for cirrhosis has been
      accumulating during the past years. In addition to the results from
      epidemiological studies, polymorphisms studies and data on twins, the concept of
      telomere shortening as a genetic risk factor for chronic liver disease and HCC
      has been proposed. Here we review the literature on telomerase mutations,
      telomere shortening and liver disease including hepatocellular carcinoma.

PMID- 24876750
TI  - Cancers in Eastern Libya: first results from Benghazi Medical Center.
AB  - AIM: To study the pattern of cancer incidence and determine the incidence rates
      in Eastern Libya (for the first time in a decade). METHODS: A hospital-based
      registry of cancer patients was formed using records from the primary oncology
      center in eastern Libya - focusing on those diagnosed in the year 2012. RESULTS:
      The most common malignancies in men were cancers of the colon (22.3%, n = 90),
      lung (20.3%, n = 82), prostate (16.1%, n = 65), pancreas (4.2%, n = 17) and liver
      (4.2%, n = 17). For women, they were found to be cancers of the breast (41.5%, n
      = 213), colon (16.4%, n = 84), uterus (8%, n = 41), ovary (5.5%, n = 28) and
      pancreas (3.1%, n = 16). Additionally age-standardized rates (ASR) were
      determined for Libya. The different cities and towns in eastern Libya were
      compared for any variation. The city of Beida in particular was found to have a
      remarkably high incidence of gastric cancer. The different findings were
      discussed and comparisons were made with past literature as well as the incidence
      rates for neighbouring countries. The incidence rates given for the eastern
      region showed differences from previously reported values (i.e., the rate of
      colon cancer was the highest in North Africa whereas other malignancies occurred
      less frequently). Potential explanations for the urban-rural difference as well
      as the difference in incidence rates were put forth. The significance of this
      study is that it establishes a baseline of cancer incidence which should be the
      backbone for any future national cancer plan in Libya. CONCLUSION: Proper
      surveillance programs need to be in place and healthcare policy should be
      adjusted to take into account the more prevalent and pressing cancers in society.

PMID- 24876748
TI  - Alcoholic hepatitis: a comprehensive review of pathogenesis and treatment.
AB  - Alcoholic hepatitis (AH) is an acute hepatic inflammation associated with
      significant morbidity and mortality. Current evidence suggests that the
      pathogenesis is the end result of the complex interplay between ethanol
      metabolism, inflammation and innate immunity. Several clinical scoring systems
      have been derived to predict the clinical outcomes of patients with AH; such as
      Child-Turcotte-Pugh score, the Maddrey discriminant function, the Lille Model,
      the model for end stage liver disease scores, and the Glasgow alcoholic hepatitis
      score. At present, Corticosteroids or pentoxifylline are the current
      pharmacologic treatment options; though the outcomes from the therapies are poor.
      Liver transplantation as the treatment of alcoholic hepatitis remains
      controversial, and in an era of organ shortage current guidelines do not
      recommend transplantation as the treatment option. Because of the limitations in
      the therapeutic options, it is no doubt that there is a critical need for the
      newer and more effective pharmacological agents to treat AH.

PMID- 24876751
TI  - Allele and haplotype frequencies for HLA-DQ in Iranian celiac disease patients.
AB  - AIM: To assess the distribution of human leukocyte antigen (HLA)-DQ2 and -DQ8 in
      Iranian celiac disease (CD) patients and compare them to healthy Iranian
      controls. METHODS: To predict the HLA-DQA1 and -DQB1 genes, we used six
      previously reported HLA-tagging single nucleotide polymorphism to determine HLA
      genotypes in 59 Iranian patients with 'biopsy-confirmed' CD and in 151 healthy
      Iranian individuals. To test the transferability of the method, 50 cases and
      controls were also typed using a commercial kit that identifies individual
      carriers of DQ2, DQ7 and DQ8 alleles. RESULTS: In this pilot study 97% of CD
      cases (n = 57) and 58% of controls (n = 87) were carriers of HLA-DQ2 and/or HLA
      DQ8 heterodimers, either in the homozygous or heterozygous state. The HLA-DQ
      pattern of these 57 CD patients: heterozygous DQ2.2 (n = 14) and homozygous DQ2.2
      (n = 1), heterozygous DQ2.5 (n = 33) and homozygous DQ2.5 (n = 8), heterozygous
      DQ8 (n = 13) and homozygous DQ8 (n = 2). Two CD patients were negative for both
      DQ2 and DQ8 (3%). CONCLUSION: The prevalence of DQ8 in our CD population was
      higher than that reported in other populations (25.4%). As reported in other
      populations, our results underline the primary importance of HLA-DQ alleles in
      the Iranian population's susceptibility to CD.

PMID- 24876752
TI  - Outcomes after stenting for malignant large bowel obstruction without radiologist
      support.
AB  - AIM: To assess outcomes after colonic stent insertion for obstructing colorectal
      malignancies performed by an endoscopist without radiologist support. METHODS:
      This is a retrospective study of all stents inserted by a single surgeon in a
      District General Hospital over an eight year period. All stents were inserted for
      patients with acute large bowel obstruction secondary to a malignant colorectal
      pathology either for palliation or as a bridge to surgery. Procedures were
      performed by a single surgeon endoscopically with fluoroscopic control in the X
      ray department but without the support of an interventional radiologist. Data was
      collected prospectively on a pre-designed database. RESULTS: The indication for
      all stent procedures was an obstructing colorectal malignancy. Out of 53
      patients, the overall success rate was 90.6%. Eight patients had a stent intended
      as a bridge to surgery and 45 as a palliative procedure. Technical success was
      achieved in 50 out of 53 procedures (94.3%) and clinical success in 48 of those
      remaining 50 (96.0%). Those with unsuccessful technical or clinical procedures
      went on to have defunctioning stomas to treat their obstruction. There were six
      complications from the technically successful stents (12.0%). These included one
      migration, one persisting obstructive symptoms and four cases of tumour
      overgrowth of the stents at a later date. Haemorrhagic complications, perforation
      or mortality were not observed in our series. Our results are comparable to
      several other studies assessing stent outcomes for obstructing bowel cancer.
      CONCLUSION: Our data suggests that colorectal stents can be inserted without
      radiologist support by an adequately trained individual with good outcomes.

PMID- 24876753
TI  - LncRNAs expression signatures of hepatocellular carcinoma revealed by microarray.
AB  - AIM: To analyze the expression profiles of long non-coding RNAs (lncRNAs) in
      hepatocellular carcinoma. METHODS: Hepatocellular carcinoma (HCC) tissues and
      matched adjacent non-tumor (NT) liver tissues were collected from 29 patients
      with HCC, immediately after liver resection, between March 2011 and July 2013.
      The diagnosis of HCC was made based on histological examination. Differentially
      expressed lncRNAs between HCC and NT tissues were revealed through microarray
      based lncRNAs expression profiling. Further, quantification of selected lncRNAs
      was performed using quantitative real-time reverse transcription polymerase chain
      reaction (qRT-PCR). RESULTS: Six hundred and fifty-nine lncRNAs were
      differentially expressed between HCC and NT tissues, of which five
      [TCONS_00018278, AK093543, D16366, ENST00000501583, NR_002819 (MALAT1)] were
      selected for validation. Four of them were significantly downregulated in HCC
      tissues compared with NT tissues (P = 0.012, 0.045, 0.000 and 0.000,
      respectively), and the expression level of MALAT1 showed no significant
      difference (P = 0.114). CONCLUSION: This study identified a set of lncRNAs
      differentially expressed in HCC tissues and provided useful information for
      exploring potential therapeutic targets and diagnostic biomarkers of this cancer.

PMID- 24876754
TI  - Clinicopathologic factors influencing the accuracy of EUS for superficial
      esophageal carcinoma.
AB  - AIM: To identify clinicopathologic factors influencing the accuracy of a high
      frequency catheter probe endoscopic ultrasonography (EUS) for superficial
      esophageal carcinomas (SECs). METHODS: A total of 126 patients with
      endoscopically suspected SEC, who underwent EUS and curative treatment at Pusan
      National University Hospital during 2005-2013, were enrolled. We reviewed the
      medical records of the 126 patients and compared EUS findings with
      histopathologic results according to clinicopathologic factors. RESULTS: A total
      of 114 lesions in 113 patients were included in the final analysis. The EUS
      assessment of tumor invasion depth was accurate in 78.9% (90/114) patients.
      Accuracy did not differ according to histologic type, tumor differentiation,
      tumor location, or macroscopic shape. However, accuracy significantly decreased
      for tumors >= 3 cm in size (P = 0.002). Overestimation and underestimation of the
      invasion depth occurred for 11 (9.6%) and 13 lesions (11.4%), respectively. In
      multivariate analyses, tumor size >= 3 cm was the only factor significantly
      associated with EUS accuracy (P = 0.031), and was specifically associated with
      the underestimation of invasion depth. CONCLUSION: EUS using a high-frequency
      catheter probe generally provides highly accurate assessments of SEC invasion
      depth, but its accuracy decreases for tumors >= 3 cm.

PMID- 24876755
TI  - Detection of promoter hypermethylation of Wnt antagonist genes in fecal samples
      for diagnosis of early colorectal cancer.
AB  - AIM: To investigate the feasibility of detecting aberrantly hypermethylated Wnt
      antagonist gene promoters (SFRP2 and WIF-1) in fecal DNA as non-invasive
      biomarkers for early colorectal cancer (CRC). METHODS: The methylation-specific
      polymerase chain reaction assay was performed to blindly analyze the methylation
      status of SFRP2 and WIF-1 gene promoters in fecal samples from 48 subjects with
      CRC, 35 with adenomas, 32 with hyperplastic polyps and 30 endoscopically normal
      subjects. Additionally, we compared the diagnostic efficiency of measuring the
      hypermethylated SFRP2 and WIF-1 genes in the feces to the fecal occult blood test
      (FOBT) for the early detection of CRC. RESULTS: Hypermethylated SFRP2 was
      detected in the feces of 56.3% (27/48) of CRC cases, 51.4% (18/35) of adenoma
      cases and 12.5% (4/32) of patients with hyperplastic polyps. The hypermethylation
      of WIF-1 was detected in 60.4% (29/48), 45.7% (16/35) and 18.7% (6/32) of fecal
      samples from CRC, adenoma and hyperplastic polyp patients, respectively. At least
      one hypermethylated gene was detected in 81.3% (39/48) of CRC and 65.7% (23/35)
      of adenoma samples. In contrast, only a hypermethylated WIF-1 gene was detected
      in one case of normal fecal samples. Moreover, no significant associations were
      observed between SFPR2 and WIF-1 hypermethylation and clinicopathological
      features. Additionally, 81.8% of CRC cases diagnosed as Dukes A stage or advanced
      adenomas had at least one hypermethylated gene detected, while the detection rate
      with the FOBT was only 31.8% (P < 0.001). CONCLUSION: Hypermethylated SFRP2 and
      WIF-1 genes in fecal DNA are novel and promising molecular biomarkers that have
      great diagnostic potential for early CRC.

PMID- 24876756
TI  - Prognostic and clinicopathological significance of glypican-3 overexpression in
      hepatocellular carcinoma: a meta-analysis.
AB  - AIM: To investigate the prognostic and clinicopathological significance of
      glypican-3 (GPC3) overexpression in hepatocellular carcinoma (HCC). METHODS:
      Publications were searched using PubMed, EMBASE, the Cochrane Library and the
      Chinese Biomedical Literature Database up to March 2013. Inclusion and exclusion
      criteria were established to screen eligible studies for meta-analysis. The
      hazard ratios (HRs) of the eligible studies were pooled using RevMan 5.2 software
      to evaluate the impact of GPC3 overexpression on overall survival (OS) and
      disease-free survival (DFS) in HCC patients. The correlation between GPC3
      expression and clinicopathological parameters of HCC was also analyzed. RESULTS:
      A total of five studies with 493 patients were included in the meta-analysis. The
      combined HRs indicated that GPC3 overexpression can predict poor OS (n = 362 in 3
      studies, HR = 2.18, 95%CI: 1.47-3.24, Z = 3.86, P = 0.0001) and DFS (n = 325 in 3
      studies, HR = 2.05, 95%CI: 1.43-2.93, Z = 3.94, P < 0.0001) in HCC patients
      without heterogeneity. Egger's and Begg's tests were applied to detect
      publication bias, and the results showed that there was no evidence of
      publication bias detected in the OS studies (the P value for Egger's test was
      0.216) or DFS studies (the P value for Egger's test was 0.488). The combined odds
      ratios (ORs) suggested that GPC3 expression tends to be associated with tumor
      vascular invasion (OR = 2.74, 95%CI: 1.15-6.52, P = 0.02), hepatic cirrhosis (OR
      = 2.10, 95%CI: 1.31-3.36, P = 0.002), poor tumor differentiation (OR = 0.22,
      95%CI: 0.13-0.40, P < 0.00001) and advanced TNM stage (OR = 0.31, 95%CI: 0.18
      0.51, P < 0.00001). CONCLUSION: From this study, we conclude that GPC3
      overexpression tends to be associated with a poor prognosis (poor OS or DFS) in
      HCC.

PMID- 24876757
TI  - No association of G-protein beta polypeptide 3 polymorphism with irritable bowel
      syndrome: evidence from a meta-analysis.
AB  - AIM: To clarify the associations between G-protein beta polypeptide 3 (GNB3)
      C825T polymorphism and risk of the irritable bowel syndrome (IBS) by a meta
      analysis. METHODS: We searched relevant studies in PubMed, EMBASE, CNKI, Google
      Scholar, Ovid and Cochrane library prior to October 2013. The strengths of the
      associations between GNB3 C825T polymorphism and IBS risk were estimated by odds
      ratios (ORs) with 95% confidence interval (CIs). RESULTS: We identified seven
      case-control studies with 1085 IBS cases and 1695 controls for the analysis. We
      found no significantly associations of GNB3 C825T polymorphism with IBS risk in
      the overall population (CC vs TT, OR = 1.12, 95%CI: 0.86-1.45; CC + CT vs TT, OR
      = 1.17, 95%CI: 0.92-1.49; TT + CT vs CC, OR = 0.93, 95%CI: 0.80-1.08; C vs T, OR
      = 1.08, 95%CI: 0.97-1.21). Subgroup analysis did not reveal significant
      associations either in Asian population or Caucasian population. The pooled
      results of four studies fail to show associations of GNB3 C825T polymorphism with
      subtypes of IBS (constipation-dominant type, diarrhea-dominant type and mixed
      type). CONCLUSION: The present study suggests no associations of GNB3 C825T
      polymorphism with IBS risk.

PMID- 24876758
TI  - Laparoscopic resection of synchronous gastric cancer and primary small intestinal
      lymphoma: a case report.
AB  - Synchronous gastric cancer and primary small intestinal lymphoma are extremely
      rare. A 49-year-old woman was referred to our hospital with a history of upper
      abdominal pain for two weeks and was diagnosed with synchronous cancer. During
      hospitalization, the patient underwent laparoscopic distal gastrectomy +
      resection of bilateral ovaries + partial resection of both small intestine and
      descending colon. Pathological examination revealed a synchronous cancer
      consisting of early gastric cancer with poorly differentiated adenocarcinoma
      located in mucosa, with lymph node metastasis (3+/29) (T1N1M0, stage IB); and
      diffuse large B cell lymphoma of small intestine involving descending colon and
      bilateral ovaries, with lymph node metastasis (2+/5) (Ann Arbor IIE). The patient
      recovered well, without any obvious complications and was discharged on post
      operative day 7. The patient received six cycles of chemotherapy after operation.
      She has been doing well with no evidence of recurrence for 13 mo.

PMID- 24876759
TI  - Classroom Goal Structures and HIV/Pregnancy Prevention Education in Rural High
      School Health Classrooms.
AB  - Over 5,000 adolescents enrolled in required rural high school health courses
      reported their perceptions of mastery and extrinsic goal structures in their
      health classrooms. Data were collected from all students at three time points
      (prior to HIV/pregnancy instruction, three months after instruction, and one year
      after instruction). Results indicated that classroom goal structures were related
      to both proximal and distal knowledge, attitudes, intentions, and efficacy
      beliefs. Results in particular indicate that the perception of a mastery goal
      structure in health education classrooms fosters knowledge, improved attitudes,
      enhanced efficacy beliefs, and lower intentions to have sexual intercourse.

PMID- 24876760
TI  - Choroidal neovascularization after intraocular foreign body.
AB  - We report an unusual case of choroidal neovascularization secondary to
      intraocular foreign body (IOFB) penetrating trauma. A 44-year-old man was
      referred to our department for IOFB trauma in the right eye. Vitrectomy and IOFB
      extraction was performed with good visual results. However, 2 months after
      surgery, he returned complaining of a drop in visual acuity. Choroidal
      neovascularization originating from a direct choroidal rupture at the IOFB impact
      site was observed. The patient was treated with 6-monthly intravitreal injections
      of antivascular endothelial growth factor, and showed regression of
      neovascularization and a final visual acuity of 20/80. IOFB trauma is a serious
      condition, indeed in spite of initially good results after a favorable surgical
      outcome. Choroidal neovascularization after direct traumatic choroidal rupture is
      usually aggressive and requires more active antivascular endothelial growth
      factor therapy. 

PMID- 24876761
TI  - Treatment of systemic hypertension is important for improvement of macular edema
      associated with retinal vein occlusion.
AB  - BACKGROUND: We report our findings in three cases of unilateral macular edema
      associated with retinal vein occlusion (RVO) that improved after successful
      treatment of systemic hypertension alone. METHODS: All three cases had systemic
      hypertension but no diabetes mellitus or other ocular diseases associated with
      macular edema. All patients were treated only with medication for systemic
      hypertension. Optical coherence tomography was performed to determine the foveal
      thickness before and after treatment. RESULTS: Case one was a 72-year-old woman
      with a central RVO who had macular edema in her left eye and a visual acuity (VA)
      of 20/50. Her blood pressure (BP) was 169/96 mmHg. One month after the initiation
      of a calcium blocker to treat her systemic hypertension, her BP was decreased,
      macular edema was reduced, and her VA improved to 20/20. Case two was a 62-year
      old woman with branch RVO. Her VA was 20/40 and her BP was 165/97 mmHg. Six weeks
      after initiation of medication to treat her systemic hypertension, her RVO
      related macular edema had decreased and her VA improved to 20/20. Case three was
      a 71-year-old man with branch RVO. His VA was 20/50 and his BP was 165/87 mmHg.
      One month after initiation of treatment for systemic hypertension, his RVO
      related macular edema had disappeared and his VA improved to 20/20. All three
      cases had nonischemic RVO by fluorescein angiography, and they did not develop
      ischemic changes for at least 1 year. CONCLUSION: The reduction of macular edema
      following a decrease in the systemic hypertension suggests that the edema was
      most likely caused by leakage of fluids from the blood vessels. We recommend that
      the blood pressure should be measured in all patients with macular edema before
      initiating intravitreal anti-VEGF therapy.

PMID- 24876762
TI  - Progression of nuclear sclerosis based on changes in refractive values after lens
      sparing vitrectomy in proliferative diabetic retinopathy.
AB  - BACKGROUND: Nuclear sclerosis (NS) based on the Emery-Little classification and
      refractive values after lens-sparing vitrectomy was compared between
      proliferative diabetic retinopathy (DR) patients and nondiabetic patients.
      METHODS: Progression of NS based on the Emery-Little classification and changes
      in refractive values were compared between 13 proliferative DR patients (14 eyes,
      DR group) and 14 nondiabetic patients (14 eyes, non-DR group) who underwent lens
      sparing vitrectomy. All patients revealed grade I NS based on the Emery-Little
      classification. Mean patient age and refractive value just after surgery were
      56.07 years and -0.33 diopters (D) in the DR group, and 57.06 years and -0.96 D
      in the non-DR group. RESULTS: The Emery-Little classification in the DR group at
      6 and 24 months postoperative were grade I (13 eyes)/grade II (one eye) and grade
      I (eleven eyes)/grade II (three eyes), respectively. Mean refractive values in
      the DR group at 6, 12, and 24 months postoperative were +0.28 D, +0.27 D, and
      +0.37 D, respectively. The Emery-Little classification in the non-DR group at 6
      and 24 months (or preoperative for patients undergoing cataract surgery) were
      grade I (five eyes)/grade II (eight eyes) and grade I (zero eyes)/grade II (eight
      eyes)/grade III (five eyes), respectively. The mean refractive value in the non
      DR group at 6 months postoperative was -3.20 D. All eyes exhibited myopic changes
      and progression of NS. CONCLUSION: The findings of this study show that the
      progression of NS postvitrectomy is mild, even for DR patients 50 years of age or
      older, thus suggesting the need to reconsider the indications for simultaneous
      cataract surgery with vitrectomy.

PMID- 24876763
TI  - The efficacy of bromfenac ophthalmic solution 0.07% dosed once daily in achieving
      zero-to-trace anterior chamber cell severity following cataract surgery.
AB  - PURPOSE: To evaluate the efficacy of bromfenac ophthalmic solution 0.07% dosed
      once daily in achieving zero-to-trace (0-5 cells) anterior chamber cells,
      following cataract surgery with posterior chamber intraocular lens implantation.
      METHODS: The study designed employed two Phase III, double-masked, placebo
      controlled, multicenter clinical trials of 440 subjects, randomized to either
      bromfenac ophthalmic solution 0.07% (n=222) or placebo (n=218). Subjects self
      dosed once daily, beginning 1 day before undergoing cataract surgery with
      intraocular lens implantation (day -1) and again on the day of surgery (day 0)
      and for 14 days postoperatively. Follow-up was on days 1, 3, 8, and 15. The
      outcome measures included the percentage of subjects with zero-to-trace anterior
      chamber cells at each visit, as determined by the percentage of subjects with <=5
      anterior chamber cells, overall anterior chamber cell grades, and summed ocular
      inflammation score (SOIS) (combined anterior chamber cell and flare scores).
      RESULTS: The proportion of subjects with zero-to-trace anterior chamber cells was
      significantly higher in the bromfenac 0.07% group compared with the placebo group
      as early as day 3 (P=0.0007), continued at day 8 (P<0.0001), and through day 15
      (P<0.0001). At day 15, 80.2% of subjects in the bromfenac 0.07% group achieved
      zero-to-trace anterior chamber cells compared with 47.2% of subjects who did so
      in the placebo group. The overall anterior chamber cell scores were significantly
      lower in the bromfenac 0.07% group compared with the placebo group at days 3, 8,
      and 15 (P<0.0001 at each visit). The SOIS were also significantly lower in the
      bromfenac group compared with the placebo group at days 3, 8, and 15 (P<0.0001 at
      each visit). CONCLUSION: Bromfenac ophthalmic solution 0.07%, dosed once daily
      was clinically effective in achieving zero-to-trace anterior chamber cell
      severity after cataract surgery and was superior to placebo in all anterior
      chamber cell severity and inflammation outcome measures.

PMID- 24876764
TI  - Advanced Coats' disease treated with intravitreal bevacizumab combined with laser
      vascular ablation.
AB  - PURPOSE: To evaluate the impact of intravitreal bevacizumab combined with laser
      vascular ablation in the management of advanced Coats' disease presenting with
      exudative retinal detachment. METHODS: This was a retrospective review of 24
      children that presented with exudative retinal detachments associated with
      advanced Coats' disease. Mean patient age was 62 months (range 9-160 months).
      Presenting signs included retinal detachment in 24 children (100%), vascular
      telangiectasia in 24 children (100%), and retinal ischemia in 24 children (100%).
      Twenty of 24 children presented with elevated, vascular leakage in the fovea
      (83%). Two children presented with sub-retinal fibrosis associated with presumed
      long-standing retinal detachment without evidence of rhegmatogenous retinal
      detachment. Ten patients exhibited vascular alterations in the periphery of the
      second eye without clinical evidence of exudation. All 24 children were treated
      with a large-spot-size diode laser directly to areas of abnormal telangiectatic
      vasculature. All 24 children received intravitreal bevacizumab injection.
      RESULTS: All 24 children had resolution of exudative retinal detachment, ablation
      of vascular telangiectasia, and anatomic improvement of the retina. No child
      exhibited progressive retinal detachment and no eye required enucleation. No
      cases of neovascular glaucoma were seen. Fellow eyes with peripheral vascular
      alterations showed no progression to exudative vasculopathy during the
      observation period. Intravitreal bevacizumab injection was not associated with
      endophthalmitis or systemically-observed complications. CONCLUSION: Repetitive
      intravitreal bevacizumab combined with laser vascular ablation may be utilized
      effectively for advanced Coats' disease presenting with exudative retinal
      detachment.

PMID- 24876765
TI  - Probing of congenital nasolacrimal duct obstruction with dacryoendoscope.
AB  - BACKGROUND: A congenital nasolacrimal duct obstruction (CNLDO) is a relatively
      common disease in infants. We evaluated the results of probing three patients
      with CNLDO, under direct view, with a dacryoendoscope. METHODS: Three cases of
      CNLDO were examined and treated by probing with a dacryoendoscope, under
      intravenous anesthesia. The diameter of the dacryoendoscope probe was 0.7 mm, and
      we were able to observe the inner walls of the lacrimal duct and able to guide
      the probe through the duct. RESULTS: In all cases, the site of obstruction was
      detected, and the probe was used to remove the obstruction. At 2 weeks after the
      removal of the obstruction, there was no epiphora or mucopurulent discharge in
      any of the cases. No complications were detected intra- and postoperatively.
      CONCLUSION: Although only three cases were studied, we believe that probing with
      a dacryoendoscope is a safe and effective method of treating a CNLDO. More cases
      need to be studied.

PMID- 24876769
TI  - Patient preferences and satisfaction in a multispecialty infusion center.
AB  - PURPOSE: Direct feedback from patients about their preferred modes of medication
      administration has been increasingly sought by providers to develop care programs
      that best match patient goals. Multispecialty infusion centers generally provide
      care to hematology-oncology (HO) and non-HO patients in one unit, with the same
      nursing staff. Our staff perceived that this was dissatisfying to our non-HO
      patients. We assessed patient satisfaction, as well as nursing and physician
      perceptions of patient preference/satisfaction with our infusion center, to
      determine whether a separate unit should be recommended when designing our new
      Cancer Institute Infusion Center. PATIENTS AND METHODS: A seven-question Likert
      scale satisfaction survey for patients, and a separate survey to assess nurses'
      and physicians' perception of patient satisfaction, were developed. The survey
      was administered to non-HO patients receiving infusions, doctors prescribing
      infusions, and nurses administering infusions. Results of the survey were
      compared between groups to assess differences in responses. RESULTS: Responses
      were received from 52 non-HO patients, 18 physicians, and 13 nurses. Patients had
      more satisfaction, on all survey items, with the multispecialty infusion center
      than had been realized by physicians and nurses. Analysis demonstrated that
      patients were satisfied with care in a multispecialty infusion unit and were in
      favor of continuing their care in this combined center. Total scores of patient
      surveys were significantly different (P<0.001) from those of physicians and
      nurses, who had assumed patients would prefer to have their care in a non-HO
      infusion setting. CONCLUSION: Understanding patient preferences is an important
      step in deciding the structure of infusion centers. Based on these survey
      conclusions, a combined multispecialty infusion center has been continued at our
      institution, thus improving quality by including patients in decision-making
      affecting their care.

PMID- 24876766
TI  - Molecular pharmacodynamics of new oral drugs used in the treatment of multiple
      sclerosis.
AB  - New oral drugs have considerably enriched the therapeutic armamentarium for the
      treatment of multiple sclerosis. This review focuses on the molecular
      pharmacodynamics of fingolimod, dimethyl fumarate (BG-12), laquinimod, and
      teriflunomide. We specifically comment on the action of these drugs at three
      levels: 1) the regulation of the immune system; 2) the permeability of the blood
      brain barrier; and 3) the central nervous system. Fingolimod phosphate (the
      active metabolite of fingolimod) has a unique mechanism of action and represents
      the first ligand of G-protein-coupled receptors (sphingosine-1-phosphate
      receptors) active in the treatment of multiple sclerosis. Dimethyl fumarate
      activates the nuclear factor (erythroid-derived 2)-related factor 2 pathway of
      cell defense as a result of an initial depletion of reduced glutathione. We
      discuss how this mechanism lies on the border between cell protection and
      toxicity. Laquinimod has multiple (but less defined) mechanisms of action, which
      make the drug slightly more effective on disability progression than on
      annualized relapse rate in clinical studies. Teriflunomide acts as a specific
      inhibitor of the de novo pyrimidine biosynthesis. We also discuss new unexpected
      mechanisms of these drugs, such as the induction of brain-derived neurotrophic
      factor by fingolimod and the possibility that laquinimod and teriflunomide
      regulate the kynurenine pathway of tryptophan metabolism. 

PMID- 24876768
TI  - Effectiveness of music therapy: a summary of systematic reviews based on
      randomized controlled trials of music interventions.
AB  - OBJECTIVE: The objective of this review was to summarize evidence for the
      effectiveness of music therapy (MT) and to assess the quality of systematic
      reviews (SRs) based on randomized controlled trials (RCTs). STUDY DESIGN: An SR
      of SRs based on RCTs. METHODS: Studies were eligible if they were RCTs. Studies
      included were those with at least one treatment group in which MT was applied. We
      searched the following databases from 1995 to October 1, 2012: MEDLINE via
      PubMed, CINAHL (Cumulative Index of Nursing and Allied Health Literature), Web of
      Science, Global Health Library, and Ichushi-Web. We also searched all Cochrane
      Database and Campbell Systematic Reviews up to October 1, 2012. Based on the
      International Classification of Diseases, 10th revision, we identified a disease
      targeted for each article. RESULTS: Twenty-one studies met all inclusion
      criteria. This study included 16 Cochrane reviews. As a whole, the quality of the
      articles was very good. Eight studies were about "Mental and behavioural
      disorders (F00-99)"; there were two studies on "Diseases of the nervous system
      (G00-99)" and "Diseases of the respiratory system (J00-99)"; and there was one
      study each for "Endocrine, nutritional and metabolic diseases (E00-90)",
      "Diseases of the circulatory system (I00-99)", and "Pregnancy, childbirth and the
      puerperium (O60)". MT treatment improved the following: global and social
      functioning in schizophrenia and/or serious mental disorders, gait and related
      activities in Parkinson's disease, depressive symptoms, and sleep quality.
      CONCLUSION: THIS COMPREHENSIVE SUMMARY OF SRS DEMONSTRATED THAT MT TREATMENT
      IMPROVED THE FOLLOWING: global and social functioning in schizophrenia and/or
      serious mental disorders, gait and related activities in Parkinson's disease,
      depressive symptoms, and sleep quality. MT may have the potential for improving
      other diseases, but there is not enough evidence at present. Most importantly, no
      specific adverse effect or harmful phenomenon occurred in any of the studies, and
      MT was well tolerated by almost all patients.

PMID- 24876771
TI  - Chronic disease self-management and exercise in COPD as pulmonary rehabilitation:
      a randomized controlled trial.
AB  - PURPOSE: Both exercise and self-management are advocated in pulmonary
      rehabilitation for people with chronic obstructive pulmonary disease (COPD). The
      widely used 6-week, group-based Chronic Disease Self-Management Program (CDSMP)
      increases self-reported exercise, despite supervised exercise not being a program
      component. This has been little explored in COPD. Whether adding supervised
      exercise to the CDSMP would add benefit is unknown. We investigated the CDSMP in
      COPD, with and without a formal supervised exercise component, to address this
      question. PATIENTS AND METHODS: Adult outpatients with COPD were randomized to
      the CDSMP with or without one hour of weekly supervised exercise over 6 weeks.
      The primary outcome measure was 6-minute walk test distance (6MWD). Secondary
      outcomes included self-reported exercise, exercise stage of change, exercise self
      efficacy, breathlessness, quality of life, and self-management behaviors. Within-
      and between-group differences were analyzed on an intention-to-treat basis.
      RESULTS: Of 84 subjects recruited, 15 withdrew. 6MWD increased similarly in both
      groups: CDSMP-plus-exercise (intervention group) by 18.6+/-46.2 m; CDSMP-alone
      (control group) by 20.0+/-46.2 m. There was no significant difference for any
      secondary outcome. CONCLUSION: The CDSMP produced a small statistically
      significant increase in 6MWD. The addition of a single supervised exercise
      session did not further increase exercise capacity. Our findings confirm the
      efficacy of a behaviorally based intervention in COPD, but this would seem to be
      less than expected from conventional exercise-based pulmonary rehabilitation,
      raising the question of how, if at all, the small gains observed in this study
      may be augmented.

PMID- 24876770
TI  - Depression and anxiety predict health-related quality of life in chronic
      obstructive pulmonary disease: systematic review and meta-analysis.
AB  - BACKGROUND: The causal association between depression, anxiety, and health
      related quality of life (HRQoL) in chronic obstructive pulmonary disease (COPD)
      is unclear. We therefore conducted a systematic review of prospective cohort
      studies that measured depression, anxiety, and HRQoL in COPD. METHODS: Electronic
      databases (Medline, Embase, Cumulative Index to Nursing and Allied Health
      Literature [CINAHL], British Nursing Index and Archive, PsycINFO and Cochrane
      database) were searched from inception to June 18, 2013. Studies were eligible
      for inclusion if they: used a nonexperimental prospective cohort design; included
      patients with a diagnosis of COPD confirmed by spirometry; and used validated
      measures of depression, anxiety, and HRQoL. Data were extracted and pooled using
      random effects models. RESULTS: Six studies were included in the systematic
      review; of these, three were included in the meta-analysis for depression and two
      were included for the meta-analysis for anxiety. Depression was significantly
      correlated with HRQoL at 1-year follow-up (pooled r=0.48, 95% confidence interval
      0.37-0.57, P<0.001). Anxiety was also significantly correlated with HRQoL at 1
      year follow-up (pooled r=0.36, 95% confidence interval 0.23-0.48, P<0.001).
      CONCLUSION: Anxiety and depression predict HRQoL in COPD. However, this
      longitudinal analysis does not show cause and effect relationships between
      depression and anxiety and future HRQoL. Future studies should identify
      psychological predictors of poor HRQoL in well designed prospective cohorts with
      a view to isolating the mediating role played by anxiety disorder and depression.

PMID- 24876772
TI  - Physicochemical features and transfection properties of chitosan/poloxamer
      188/poly(D,L-lactide-co-glycolide) nanoplexes.
AB  - The aim of this study was the evaluation of the effects of two emulsifiers on the
      physicochemical and technological properties of low molecular weight
      chitosan/poly (D,L-lactide-co-glycolide) (PLGA) nanoplexes and their transfection
      efficiency. Nanospheres were prepared using the nanoprecipitation method of the
      preformed polymer. The mean diameter and surface charge of the nanospheres were
      investigated by photocorrelation spectroscopy. The degree of binding of the
      plasmid with the nanoplexes was qualitatively and quantitatively determined. MTT
      (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) testing was
      performed using HeLa, RPMI8226, and SKMM1 cell lines. Flow cytometry and confocal
      laser scanning microscopy were used to determine the degree of cellular
      transfection and internalization of the nanoplexes into cells, respectively. The
      nanoplexes had a positive zeta potential, and low amounts of PLGA and poloxamer
      188 showed a mean colloidal size of ~200 nm with a polydispersity index of ~0.14.
      The nanoplexes had suitable entrapment efficiency (80%). In vitro experiments
      showed that the colloidal nanodevices did not induce significant cytotoxicity.
      The nanoplexes investigated in this study could represent efficient and useful
      nonviral devices for gene delivery. Use of low amounts of PLGA and poloxamer 188
      enabled development of a nanosphere able to transfect cells efficiently. These
      nanosystems are a helpful platform for delivery of genetic material while
      preserving therapeutic efficacy. 

PMID- 24876773
TI  - Nanosilver particles in medical applications: synthesis, performance, and
      toxicity.
AB  - Nanosilver particles (NSPs), are among the most attractive nanomaterials, and
      have been widely used in a range of biomedical applications, including diagnosis,
      treatment, drug delivery, medical device coating, and for personal health care.
      With the increasing application of NSPs in medical contexts, it is becoming
      necessary for a better understanding of the mechanisms of NSPs' biological
      interactions and their potential toxicity. In this review, we first introduce the
      synthesis routes of NSPs, including physical, chemical, and biological or green
      synthesis. Then the unique physiochemical properties of NSPs, such as
      antibacterial, antifungal, antiviral, and anti-inflammatory activity, are
      discussed in detail. Further, some recent applications of NSPs in prevention,
      diagnosis, and treatment in medical fields are described. Finally, potential
      toxicology considerations of NSPs, both in vitro and in vivo, are also addressed.

PMID- 24876774
TI  - Nanoparticles containing allotropes of carbon have genotoxic effects on
      glioblastoma multiforme cells.
AB  - The carbon-based nanomaterial family consists of nanoparticles containing
      allotropes of carbon, which may have a number of interactions with biological
      systems. The objective of this study was to evaluate the toxicity of
      nanoparticles comprised of pristine graphene, reduced graphene oxide, graphene
      oxide, graphite, and ultradispersed detonation diamond in a U87 cell line. The
      scope of the work consisted of structural analysis of the nanoparticles using
      transmission electron microscopy, evaluation of cell morphology, and assessment
      of cell viability by Trypan blue assay and level of DNA fragmentation of U87
      cells after 24 hours of incubation with 50 MUg/mL carbon nanoparticles. DNA
      fragmentation was studied using single-cell gel electrophoresis. Incubation with
      nanoparticles containing the allotropes of carbon did not alter the morphology of
      the U87 cancer cells. However, incubation with pristine graphene and reduced
      graphene oxide led to a significant decrease in cell viability, whereas
      incubation with graphene oxide, graphite, and ultradispersed detonation diamond
      led to a smaller decrease in cell viability. The results of a comet assay
      demonstrated that pristine graphene, reduced graphene oxide, graphite, and
      ultradispersed detonation diamond caused DNA damage and were therefore genotoxic
      in U87 cells, whereas graphene oxide was not. 

PMID- 24876776
TI  - Biosynthesis of silver nanoparticles using Acacia leucophloea extract and their
      antibacterial activity.
AB  - The immense potential of nanobiotechnology makes it an intensely researched field
      in modern medicine. Green nanomaterial synthesis techniques for medicinal
      applications are desired because of their biocompatibility and lack of toxic
      byproducts. We report the toxic byproducts free phytosynthesis of stable silver
      nanoparticles (AgNPs) using the bark extract of the traditional medicinal plant
      Acacia leucophloea (Fabaceae). Visual observation, ultraviolet-visible
      spectroscopy, and transmission electron microscopy (TEM) were used to
      characterize the synthesized AgNPs. The visible yellow-brown color formation and
      surface plasmon resonance at 440 nm indicates the biosynthesis of AgNP. The TEM
      images show polydisperse, mostly spherical AgNP particles of 17-29 nm. Fourier
      transform infrared spectroscopy revealed that primary amines, aldehyde/ketone,
      aromatic, azo, and nitro compounds of the A. leucophloea extract may participate
      in the bioreduction and capping of the formed AgNPs. X-ray diffraction confirmed
      the crystallinity of the AgNPs. The in vitro agar well diffusion method confirmed
      the potential antibacterial activity of the plant extract and synthesized AgNPs
      against the common bacterial pathogens Staphylococcus aureus (MTCC 737), Bacillus
      cereus (MTCC 1272), Listeria monocytogenes (MTCC 657), and Shigella flexneri
      (MTCC 1475). This research combines the inherent antimicrobial activity of silver
      metals with the A. leucophloea extract, yielding antibacterial activity-enhanced
      AgNPs. This new biomimetic approach using traditional medicinal plant (A.
      leucophloea) barks to synthesize biocompatible antibacterial AgNPs could easily
      be scaled up for additional biomedical applications. These polydisperse AgNPs
      green-synthesized via A. leucophloea bark extract can readily be used in many
      applications not requiring high uniformity in particle size or shape. 

PMID- 24876775
TI  - Antioxidative nanofullerol prevents intervertebral disk degeneration.
AB  - Compelling evidence suggests that reactive oxygen species (ROS) play a pivotal
      role in disk degeneration. Fullerol nanoparticles prepared in aqueous solution
      have been demonstrated to have outstanding ability to scavenge ROS. In this
      report, in vitro and in vivo models were used to study the efficacy of fullerol
      in preventing disk degeneration. For in vitro experiments, a pro-oxidant H2O2 or
      an inflammatory cytokine interleukin (IL)-1beta was employed to induce
      degenerated phenotypes in human nucleus pulposus cells encapsulated in alginate
      beads, and fullerol was added in the culture medium. For the animal study, an
      annulus-puncture model with rabbit was created, and fullerol was injected into
      disks. It was shown that cytotoxicity and cellular ROS level induced by H2O2 were
      significantly diminished by fullerol. IL-1beta-induced nitric oxide generation in
      culture medium was suppressed by fullerol as well. Gene-profile and biochemical
      assays showed that fullerol effectively reversed the matrix degradation caused by
      either H2O2 or IL-1beta. The animal study delineated that intradiskal injection
      of fullerol prevented disk degeneration, increasing water and proteoglycan
      content and inhibiting ectopic bone formation. These results suggest that
      antioxidative fullerol may have a potential therapeutic application for disk
      degeneration. 

PMID- 24876778
TI  - Second case report of successful electroconvulsive therapy for a patient with
      schizophrenia and severe hemophilia A.
AB  - Electroconvulsive therapy (ECT) is used for medication-resistant and life
      threatening mental disorders, and therefore it occupies an important position in
      psychiatric treatment. ECT reportedly increases intracranial pressure and is
      suspected of increasing the risk of intracranial hemorrhage, especially in
      patients with hemorrhagic diseases such as hemophilia. A decrease in or loss of
      blood coagulation factors, including factor VIII and factor IX, are found in
      hemophilia A and B, respectively. Psychiatrists may hesitate to perform ECT on
      patients with bleeding tendencies, such as in hemophilia. Here, we report the
      successful use of ECT on a neuroleptic-resistant patient with schizophrenia and
      severe hemophilia A. We performed ECT 16 times supplemented with coagulation
      factor VIII to prevent intracranial and systematic hemorrhage. We administered
      factor VIII concentrates to the patient to keep factor VIII activity at 30%-40%
      during ECT. The patient did not show bleeding or other complications during the
      ECT sessions. We suggest that pretreatment with factor VIII can help manage the
      increased risks of intracranial and systematic bleeding during ECT that is
      present in patients with hemophilia A. The present report supports the idea of
      performing ECT safely on patients with hemophilia A by administering factor VIII.

PMID- 24876777
TI  - Olanzapine in Chinese patients with schizophrenia or bipolar disorder: a
      systematic literature review.
AB  - BACKGROUND: Despite the burden of schizophrenia and bipolar disorder in the
      Chinese population, country-specific data to guide practitioners regarding
      antipsychotic therapy are lacking. The primary aim of this systematic review was
      to examine evidence of the efficacy, effectiveness, and safety of olanzapine in
      Chinese populations. METHODS: A systematic literature search was conducted using
      databases covering international and Chinese core journals using search terms
      related to schizophrenia and bipolar disorder, specified countries (People's
      Republic of China, Hong Kong, Taiwan), and olanzapine treatment. Following
      initial screening, inclusion and exclusion criteria were applied to the search
      results to identify relevant studies from which data were extracted. RESULTS: A
      total of 489 publications were retrieved and 61 studies were identified for
      inclusion. Most studies were related to schizophrenia (n=54), with six studies
      related to bipolar disorder and one study related to both conditions. The quality
      of study methods and reporting in international journals was noticeably better
      than in Chinese language journals. Most studies included relatively small patient
      populations and were of short duration. The efficacy of olanzapine in Chinese
      populations was confirmed by multiple comparative and noncomparative studies that
      found statistically significant reductions in symptom measures in studies
      conducted for >=6 weeks (schizophrenia) or >=3 weeks (bipolar disorder). Findings
      related to effectiveness (treatment discontinuation, quality of life, and
      neurocognitive improvements) were generally consistent with those observed in non
      Chinese populations. No new safety signals specific for Chinese populations were
      raised for olanzapine. CONCLUSION: Chinese and non-Chinese populations with
      schizophrenia or bipolar disorder treated with olanzapine display broadly similar
      responses. Differences between these populations, especially in relation to the
      relative efficacy of olanzapine versus other antipsychotics, may warrant further
      investigation via studies incorporating both populations. Use of local data to
      provide evidence for practice guidelines should be encouraged, and may promote
      ongoing improvements in the quality of research and study reporting.

PMID- 24876780
TI  - Temperament, character traits, and alexithymia in patients with panic disorder.
AB  - BACKGROUND: The primary aim of the present study was to compare temperament and
      character traits and levels of alexithymia between patients with panic disorder
      and healthy controls. METHODS: Sixty patients with panic disorder admitted to the
      psychiatry clinic at Firat University Hospital were enrolled in the study, along
      with 62 healthy age-matched and sex-matched controls. The Structured Clinical
      Interview for DSM-IV axis I (SCID-I), Temperament and Character Inventory (TCI),
      Toronto Alexithymia Scale (TAS-20), and Panic Agoraphobia Scale (PAS) were
      administered to all subjects. RESULTS: Within the temperament dimension, the mean
      subscale score for harm avoidance was significantly higher in patients with panic
      disorder than in controls. With respect to character traits, mean scores for self
      directedness and cooperativeness were significantly lower than in healthy
      controls. Rates of alexithymia were 35% (n=21) and 11.3% (n=7) in patients with
      panic disorder and healthy controls, respectively. The difficulty identifying
      feelings subscale score was significantly higher in patients with panic disorder
      (P=0.03). A moderate positive correlation was identified between PAS and TAS
      scores (r=0.447, P<0.01). Moderately significant positive correlations were also
      noted for PAS and TCI subscale scores and scores for novelty seeking, harm
      avoidance, and self-transcendence. CONCLUSION: In our study sample, patients with
      panic disorder and healthy controls differed in TCI parameters and rate of
      alexithymia. Larger prospective studies are required to assess for causal
      associations.

PMID- 24876779
TI  - Factors associated with early response to olanzapine and clinical and functional
      outcomes of early responders treated for schizophrenia in the People's Republic
      of China.
AB  - BACKGROUND: The aims of this analysis were to identify factors associated with
      early response (at 4 weeks) to olanzapine treatment and to assess whether early
      response is associated with better longer-term outcomes for patients with
      schizophrenia in the People's Republic of China. METHODS: A post hoc analysis of
      a multi-country, 6-month, prospective, observational study of outpatients with
      schizophrenia or bipolar mania who initiated or switched to treatment with oral
      olanzapine was conducted using data from the Chinese schizophrenia subgroup
      (n=330). Factors associated with early response were identified using a stepwise
      logistic regression with baseline clinical characteristics, baseline
      participation in a weight control program, and adherence with antipsychotics
      during the first 4 weeks of treatment. Mixed models for repeated measures with
      baseline covariates were used to compare outcomes over time between early
      responders and early nonresponders to olanzapine. RESULTS: One hundred and thirty
      patients (40%) achieved an early response. Early response was independently
      predicted by higher baseline Clinical Global Impressions-Severity score (odds
      ratio [OR] 1.51, 95% confidence interval [CI] 1.15-1.97), fewer years since first
      diagnosis (OR 0.94, CI 0.90-0.98), a greater number of social activities (OR
      1.22, CI 1.05-1.40), participation in a weight control program (OR 1.81, CI 1.04
      3.15), and high adherence with antipsychotics during the first 4 weeks of
      treatment (OR 2.98, CI 1.59-5.58). Relative to early nonresponders, early
      responders were significantly more likely to meet treatment response criteria at
      endpoint, had significantly greater symptom improvement (Clinical Global
      Impressions-Severity), and had significantly greater improvement in functional
      outcomes (all P<0.05). CONCLUSION: High levels of adherence to prescribed
      antipsychotics and participation in a weight control program were associated with
      early response to olanzapine in Chinese patients with schizophrenia. Early
      response was associated with greater improvement in symptomatic, functional, and
      quality of life outcomes at 6 months compared with early nonresponse. Current
      findings are consistent with previous research outside of the People's Republic
      of China.

PMID- 24876781
TI  - Rheumatoid arthritis in Jordan: a cross sectional study of disease severity and
      associated comorbidities.
AB  - Treating rheumatoid arthritis (RA) to target is advocated using disease activity
      measures. The impact of RA on the general health status of affected patients in
      Jordan is not well described. This study reported the severity of RA in Jordan
      and its association with consequent disabilities and comorbidities. A cross
      sectional, observational study was conducted at King Abdullah University Hospital
      in the north of Jordan. All patients who were diagnosed with RA were included.
      Patients' demographics, comorbidities, disease activity score (DAS 28), and
      clinical disease activity index (CDAI) were collected. Both DAS 28 and CDAI were
      utilized to categorize RA disease activity. A total of 465 patients with RA were
      included: 82% were females; mean age +/- standard deviation (SD) was 47.62+/-14.6
      years; and mean disease duration +/- SD was 6+/-4.45 years. The mean +/- SD for
      the DAS 28 and CDAI was 5.1+/-1.5 and 23+/-14.2, respectively. According to the
      DAS 28, 51% of the patients were in the high disease activity category and only
      5% were in remission. On the other hand, according to the CDAI, 44% were in the
      high disease activity category and only 1% were in remission. In Jordan, patients
      with RA have a high severe disease rate and a low remission rate. The disease is
      often progressive and associated with comorbidities that need to be managed. 

PMID- 24876782
TI  - Radiation dose to the nodal regions during prone versus supine breast
      irradiation.
AB  - BACKGROUND: Prone positioning for breast radiotherapy is preferable when the aim
      is a reduction of the dose to the ipsilateral lung or the heart in certain left
      sided cases. MATERIALS AND METHODS: In 100 breast cancer cases awaiting
      postoperative whole-breast radiotherapy, conformal radiotherapy plans were
      prospectively generated in both prone and supine positions. The axillary nodal
      region (levels I-III) and internal mammary (IM) lymph-node region in the upper
      three intercostal spaces were retrospectively contoured. The mean doses to the
      nodal regions and the volume receiving 25 Gy (V25Gy), V45Gy, and V47.5Gy were
      compared between the two treatment positions. RESULTS: In most cases, the doses
      to axillary levels I-III and the IM lymph nodes were inadequate, regardless of
      the treatment position. The nodal doses were significantly lower in the prone
      than in the supine position. The radiation doses to levels II-III and IM nodes
      were especially low. The V45Gy and V47.5Gy of the level I axillary lymph nodes
      were 54.6% and 40.2%, respectively, in the supine, and 3.0% and 1.7%,
      respectively, in the prone position. In the supine position, only 17 patients
      (17%) received a mean dose of 45 Gy to the axillary level I nodes. CONCLUSION:
      The radiation dose to the axillary and IM lymph nodes during breast radiotherapy
      is therapeutically insufficient in most cases, and is significantly lower in the
      prone position than in the supine position.

PMID- 24876783
TI  - Investigation and analysis of oncologists' knowledge of morphine usage in cancer
      pain treatment.
AB  - PURPOSE: To examine oncologists' knowledge of cancer pain and morphine's clinical
      application in the People's Republic of China. In addition, this study analyzes
      and discusses the negative factors that currently affect the clinical application
      of morphine. PATIENTS AND METHODS: A questionnaire survey was given to a random
      sample of 150 oncologists from Tianjin Medical University Cancer Institute and
      Hospital. The statistical results were analyzed and processed using SPSS version
      21.0 and Matlab version 2012a statistical software. Single-factor analysis of
      variance, Kruskal-Wallis nonparametric test, and independent samples t-test were
      adopted to analyze the difference in knowledge scores of morphine usage. The
      study also identified major impediment factors on clinical use of morphine.
      RESULTS: Among the 127 respondents, morphine controlled-release tablets were the
      most popular drug chosen to treat severe cancer pain (76 respondents, 35.8%).
      Participants who reported having received training in cancer pain management and
      drug use demonstrated a significantly higher mean score of basic knowledge
      compared with their untrained peers (11.51+/-2.60 versus 9.28+/-3.68, t=2.48,
      P=0.022). The top four barriers to widespread clinical use of morphine for cancer
      pain were 1) insufficient analgesia administration training for medical
      personnel, 2) poor patient compliance, 3) drug side effects, and 4) concerns
      surrounding drug addiction. CONCLUSION: The oncologists in the People's Republic
      of China simultaneously lack comprehensive knowledge and harbor misconceptions
      with regard to cancer pain treatment and morphine's clinical application.
      Creating professional training initiatives for oncologists is necessary to
      enhance their awareness and expertise in morphine use for cancer pain treatment.

PMID- 24876784
TI  - Clinical potential of bevacizumab in the treatment of metastatic and locally
      advanced cervical cancer: current evidence.
AB  - The addition of bevacizumab to established therapies for metastatic and locally
      advanced cervical cancer is an area of evolving research and a potential strategy
      toward improving historically suboptimal outcomes for women with advanced
      disease. Bevacizumab, when added to first-line chemotherapy, has now been shown
      to improve overall survival among women with metastatic cervical cancer, and
      recent Phase II data suggests it is safe and effective for patients with locally
      advanced disease treated with curative intent. Here we review the rationale and
      current evidence for bevacizumab in clinical practice, with an emphasis on the
      emerging role of bevacizumab in the treatment of metastatic and locally advanced
      cervical cancer. 

PMID- 24876785
TI  - Treating advanced non-small-cell lung cancer in Chinese patients: focus on
      icotinib.
AB  - Icotinib hydrochloride is an orally administered small-molecule reversible
      tyrosine kinase inhibitor that has been independently researched and developed
      and has independent intellectual property rights in the People's Republic of
      China. Clinical trials have demonstrated that the response to icotinib among
      advanced non-small-cell lung cancer (NSCLC) patients who received at least one
      platinum-based chemotherapy regimen was not inferior to gefitinib. Since being
      launched August 2011 in the People's Republic of China, icotinib has been widely
      used in clinics, and has become an important treatment option for Chinese
      patients with advanced NSCLC. The present study presents the Phase I, II, and III
      clinical trials of icotinib and discusses current clinical applications in the
      People's Republic of China and future research directions. 

PMID- 24876786
TI  - Clinical utility of telavancin for treatment of hospital-acquired pneumonia:
      focus on non-ventilator-associated pneumonia.
AB  - BACKGROUND: Hospital-acquired pneumonia (HAP) is the most common health care
      associated infection contributing to death. Studies have indicated that there may
      be differences in the causative pathogens and outcomes of ventilator-associated
      pneumonia (VAP) and non-ventilator-associated pneumonia (NV-HAP). However, with
      limited NV-HAP-specific data available, treatment is generally based on data from
      studies of VAP. The Phase 3 Assessment of Telavancin for Treatment of Hospital
      Acquired Pneumonia (ATTAIN) studies were two double-blind randomized controlled
      trials that demonstrated the non-inferiority of telavancin to vancomycin for
      treatment of Gram-positive HAP. We conducted a post hoc subgroup analysis of
      patients enrolled in the ATTAIN studies who had NV-HAP. METHODS: Data from the
      two ATTAIN studies were pooled, and patients with NV-HAP were analyzed. The all
      treated (AT) population consisted of all randomized patients who received >=1
      dose of study medication, and the clinically evaluable (CE) population consisted
      of AT patients who were protocol-adherent or who died on or after study day 3,
      where death was attributable to the HAP episode under study. The primary endpoint
      was clinical response (cure, failure, or indeterminate) at the follow-up/test of
      cure visit, conducted 7-14 days after the end of therapy. RESULTS: A total of
      1,076 patients (71.6% of overall ATTAIN AT population) had NV-HAP (533 and 543
      patients in the telavancin and vancomycin treatment groups, respectively).
      Clinical cure rates in the CE population were similar for patients with NV-HAP
      treated with telavancin and vancomycin (83.1% [201/242] and 84.1% [233/277],
      respectively). In patients with methicillin-resistant Staphylococcus aureus
      isolated at baseline, cure rates in the CE population were 74.8% (77/103) for
      telavancin and 79.3% (96/121) for vancomycin. The incidence of adverse events,
      serious adverse events, and deaths in patients with NV-HAP was similar whether
      patients received telavancin or vancomycin. CONCLUSION: This post hoc subgroup
      analysis of the ATTAIN studies demonstrated similar cure rates for telavancin and
      vancomycin for treatment of NV-HAP.

PMID- 24876787
TI  - Health economics evidence for medical nutrition: are these interventions value
      for money in integrated care?
AB  - BACKGROUND: Health care decision-makers have begun to realize that medical
      nutrition plays an important role in the delivery of care, and it needs to be
      seen as a sole category within the overall health care reimbursement system to
      establish the value for money. Indeed, improving health through improving
      patients' nutrition may contribute to the cost-effectiveness and financial
      sustainability of health care systems. Medical nutrition is regulated by a
      specific bill either in Europe or in the United States, which offers specific
      legislations and guidelines (as provided to patients with special nutritional
      needs) and indications for nutritional support. Given that the efficacy of
      medical nutrition has been proven, one can wonder whether the heterogeneous
      nature of its coverage/reimbursement across countries might be due to the lack of
      health-related economic evidence or value-for-money of nutritional interventions.
      This paper aims to address this knowledge gap by performing a systematic
      literature review on health economics evidence regarding medical nutrition, and
      by summarizing the results of these publications related to the value for money
      of medical nutrition interventions. METHODS: A systematic literature search was
      initiated and executed based on a predefined search protocol following the
      population, intervention, comparison, and outcomes (PICO) criteria. Following the
      systematic literature search of recently published literature on health economics
      evidence regarding medical nutrition, this study aims to summarize the results of
      those publications that are related to the value for money of medical nutrition
      interventions. The evaluations were conducted by analyzing different medical
      nutrition according to their indications, the economic methodology or perspective
      adopted, the cost source and utility measures, selected efficiency measures, as
      well as the incremental cost-effectiveness ratio. RESULTS: A total of 225
      abstracts were identified for the detailed review, and the data were entered into
      a data extraction sheet. For the abstracts that finally met the predefined
      inclusion criteria (n=53), full-text publications were obtained via PubMed,
      subito, or directly via each journal's Webpage for further assessment. After a
      detailed review of the full text articles, 34 publications have been qualified
      for a thorough data extraction procedure. When differentiating the resulting
      articles in terms of their settings, 20 studies covered inpatients, whereas 14
      articles covered outpatients, including patients in community centers. When
      reviewing the value-for-money evaluations, the indications showed that the
      different results were mostly impacted by the different perspectives adopted and
      the comparisons that were made. In order to draw comprehensive conclusions, the
      results were split according to the main indications and diseases. DISCUSSION:
      The systematic literature search has shown that there is not only an interest in
      health economics and its application in medical nutrition, but that there is a
      lot of ongoing research in this area. Based on the underlying systematic
      analysis, it has been shown that medical nutrition interventions offer value for
      money in the different health care settings, particularly for the specific
      disease areas that have been pointed out. CONCLUSION: Based on the systematic
      literature search that was performed, it was shown that medical nutrition
      interventions offer value for money in the different health care settings.
      Although medical nutrition has been the topic of some health economic analyses,
      the usual willingness to pay threshold used in health care rarely was applied.
      Often, these products are either directly part of a lump sum in the financing
      system (for example, diagnosis-related groups), or they are covered as out-of
      pocket payments by patients directly. More research would be necessary to better
      understand how medical nutrition interventions can be optimally funded by the
      health care system, given the clinical value they bring to patients in their
      recovery process.

PMID- 24876788
TI  - Conversion of the Seattle Angina Questionnaire into EQ-5D utilities for ischemic
      heart disease: a systematic review and catalog of the literature.
AB  - BACKGROUND: There is a paucity of preference-based (utility) measures of health
      related quality of life for patients with ischemic heart disease (IHD); in
      contrast, the Seattle Angina Questionnaire (SAQ) is a widely used descriptive
      measure. Our objective was to perform a systematic review of the literature to
      identify IHD studies reporting SAQ scores in order to apply a mapping algorithm
      to convert these to preference-based scores for secondary use in economic
      evaluations. METHODS: Relevant articles were identified in MEDLINE (Ovid), EMBASE
      (Ovid), Cochrane Library (Wiley), HealthStar (Ovid), and PubMed from inception to
      2012. We previously developed and validated a mapping algorithm that converts SAQ
      descriptive scores to European Quality of Life-5 Dimensions (EQ-5D) utility
      scores. In the current study, this mapping algorithm was used to estimate EQ-5D
      utility scores from SAQ scores. RESULTS: Thirty-six studies met the inclusion
      criteria. The studies were categorized into three groups, ie, general IHD (n=13),
      acute coronary syndromes (n=4), and revascularization (n=19). EQ-5D scores for
      patients with general IHD were in the range of 0.605-0.843 at baseline, and
      increased to 0.649-0.877 post follow-up. EQ-5D scores for studies of patients
      with recent acute coronary syndromes increased from 0.706-0.796 at baseline to
      0.795-0.942 post follow-up. The revascularization studies had EQ-5D scores in the
      range of 0.616-0.790 at baseline, and increased to 0.653-0.928 after treatment;
      studies that focused only on coronary artery bypass grafting increased from 0.643
      0.788 at baseline to 0.653-0.928 after grafting, and studies that focused only on
      percutaneous coronary intervention increased in score from 0.616-0.790 at
      baseline to 0.668-0.897 after treatment. CONCLUSION: In this review, we provide a
      catalog of estimated health utility scores across a wide range of disease
      severity and following various interventions in patients with IHD. Our catalog of
      EQ-5D scores can be used in IHD-related economic evaluations.

PMID- 24876789
TI  - Measuring disease activity in Crohn's disease: what is currently available to the
      clinician.
AB  - Crohn's disease (CD) is a chronic inflammatory bowel disease characterized by a
      relapsing-remitting clinical behavior and dominated by intestinal inflammation.
      Being a chronic disorder that with time develops into a disabling disease, it is
      important to monitor the severity of inflammation to assess the efficacy of
      medication, rule out complications, and prevent progression. This is particularly
      true now that the goals of treatment are mucosal healing and deep remission.
      Endoscopy has always been the gold standard for assessing mucosal activity in CD,
      but its use is limited by its invasiveness and its inability to examine the small
      intestine, proximal to the terminal ileum. Enteroscopy and the less invasive
      small bowel capsule endoscopy enable the small bowel to be thoroughly explored
      and scores are emerging for classifying small bowel disease activity. Cross
      sectional imaging techniques (ultrasound, magnetic resonance, computed
      tomography) are emerging as valid tools for monitoring CD patients, assessing
      inflammatory activity in the mucosa and the transmucosal extent of the disease,
      and for excluding extra-intestinal complications. Neither endoscopy nor imaging
      are suitable for assessing patients frequently, however. Noninvasive markers such
      as C-reactive protein, and fecal biomarkers such as calprotectin and lactoferrin,
      are therefore useful to confirm the inflammatory burden of the disease and to
      identify patients requiring further investigations. 

PMID- 24876790
TI  - Influence of oncogenic transcription factors on chromatin conformation and
      implications in prostate cancer.
AB  - In recent years, facilitated by rapid technological advances, we are becoming
      more adept at probing the molecular processes, which take place in the nucleus,
      that are crucial for the hierarchical regulation and organization of chromatin
      architecture. With an unprecedented level of resolution, a detailed atlas of
      chromosomal structures (histone displacement, variants, modifications, chromosome
      territories, and DNA looping) and mechanisms underlying their establishment,
      provides invaluable insight into physiological as well as pathological phenomena.
      In this review, we will focus on prostate cancer, a prevalent malignancy in men
      worldwide, and for which a curative treatment strategy is yet to be attained. We
      aim to catalog the most frequently observed oncogenic alterations associated with
      chromatin conformation, while emphasizing the TMPRSS2-ERG fusion, which is found
      in more than one-half of prostate cancer patients and its functions in
      compromising the chromatin landscape in prostate cancer. 

PMID- 24876792
TI  - Efficacy and tolerability of celecoxib and naproxen versus placebo in Hispanic
      patients with knee osteoarthritis.
AB  - BACKGROUND: Celecoxib is an effective treatment for osteoarthritis (OA). However,
      information on its efficacy and safety profile in different racial/ethnic groups
      is limited. Noticeable differences among racial groups are found in other disease
      states, but a thorough investigation of OA is lacking. The objective of this
      study was to determine if celecoxib 200 mg once daily is as effective as naproxen
      500 mg twice daily in the treatment of OA of the knee in Hispanic patients.
      METHODS: Hispanic patients aged >=45 years with knee OA were randomized to
      receive celecoxib 200 mg once daily, naproxen 500 mg twice daily, or placebo for
      6 weeks. The primary efficacy variable was the change in Patient's Assessment of
      Arthritis Pain at 6 weeks compared with baseline. Secondary variables were change
      in Patient's and Physician's Global Assessments of Arthritis from baseline to
      week 6/early termination, change in Western Ontario and McMaster Universities OA
      Index (WOMAC) from baseline to week 6/early termination, change in American Pain
      Society pain score, Pain Satisfaction Scale, Patient Health Questionnaire (PHQ
      9), and measurements of upper gastrointestinal tolerability. RESULTS: In total,
      239 patients completed the trial (96 celecoxib, 96 naproxen, 47 placebo).
      Celecoxib was as effective as naproxen in reducing OA pain (least squares mean
      change from baseline [standard error] -39.7 [2.7] for celecoxib and -36.9 [2.6]
      for naproxen). Patient's and Physician's Global Assessments of Arthritis, WOMAC
      scores, upper gastrointestinal tolerability, Pain Satisfaction Scale, and PHQ-9
      showed no statistically significant differences between the celecoxib and
      naproxen groups. The incidence of adverse events and treatment-related adverse
      events were similar among the treatment groups. CONCLUSION: Celecoxib 200 mg once
      daily was as effective as naproxen 500 mg twice daily in the treatment of signs
      and symptoms of knee OA in Hispanic patients. Celecoxib was shown to be safe and
      well tolerated in this patient population.

PMID- 24876791
TI  - Angelman syndrome: review of clinical and molecular aspects.
AB  - "Angelman syndrome" (AS) is a neurodevelopmental disorder whose main features are
      intellectual disability, lack of speech, seizures, and a characteristic
      behavioral profile. The behavioral features of AS include a happy demeanor,
      easily provoked laughter, short attention span, hypermotoric behavior, mouthing
      of objects, sleep disturbance, and an affinity for water. Microcephaly and subtle
      dysmorphic features, as well as ataxia and other movement disturbances, are
      additional features seen in most affected individuals. AS is due to deficient
      expression of the ubiquitin protein ligase E3A (UBE3A) gene, which displays
      paternal imprinting. There are four molecular classes of AS, and some genotype
      phenotype correlations have emerged. Much remains to be understood regarding how
      insufficiency of E6-AP, the protein product of UBE3A, results in the observed
      neurodevelopmental deficits. Studies of mouse models of AS have implicated UBE3A
      in experience-dependent synaptic remodeling. 

PMID- 24876794
TI  - Effects of nutrition counseling and monitoring on the weight and hemoglobin of
      patients receiving antiretroviral therapy in Ebonyi State, Southeast Nigeria.
AB  - INTRODUCTION: The relationship between human immunodeficiency virus (HIV) and
      malnutrition is easily explained, and the etiology of malnutrition in HIV disease
      is believed to be multifactorial. It therefore follows that ongoing assessment of
      nutritional and medical status is crucial to quality nutrition care for every
      person living with HIV. The aim of this study was to find out the effect of
      nutritional counseling and monitoring, using personalized dietary prescriptions,
      on the body mass index (BMI) and hemoglobin of patients who are HIV-infected and
      also receiving highly active antiretroviral drugs. METHODS: A total of 84
      patients were selected using simple random sampling and allocated into
      intervention and control groups. Nutritional counseling and monitoring was done
      for the intervention group, while only weight, height, and hemoglobin
      concentration were monitored for the control group. At the end of 6 months, the
      differences in mean body mass index (BMI) and hemoglobin concentrations of the
      intervention and control groups were compared using the Student's t-test.
      Statistical level of significance was put at P<0.05. RESULTS: Among respondents,
      30.96% were males and 69.04% were females, and the mean age of the intervention
      group was 33.8 years and was 35.3 in the control group. After 6 months of study,
      the difference in the mean BMI among the males of both groups (24.9 kg/m(2)
      [intervention] and 24.3 kg/m(2) [control]) was not significant (P=0.53) but was
      significant among the females (24.9 kg/m(2) [intervention group] versus 21.8
      kg/m(2) [control group]) (P=0.0005). The difference in mean hemoglobin
      concentration between the intervention and control groups for both males and
      females were statistically significant (12.2 mg/dL for males in the intervention
      group and 11.0 mg/dL for males in the control group [P=0.005]; 11.9 mg/dL for
      females in the intervention group and 11.0 mg/dL for females in the control group
      [P=0.010. CONCLUSION: Nutrition intervention is important in the management of
      people living with HIV/acquired immunodeficiency disease (AIDS) while on
      antiretroviral therapy. This can be achieved through nutritional counseling and
      monitoring.

PMID- 24876793
TI  - Critical appraisal of elvitegravir in the treatment of HIV-1/AIDS.
AB  - Human immunodeficiency virus type 1 (HIV-1) integrase inhibitors belong to a
      novel class of antiretroviral drugs with high potency and better tolerability.
      Elvitegravir (EVG) is the second integrase inhibitor approved by the US Food and
      Drug Administration when administered in combination with a novel
      pharmacoenhancer, cobicistat (COBI), and two nucleoside/nucleotide reverse
      transcriptase inhibitors, emtricitabine (FTC) and tenofovir disoproxil fumarate
      (TDF). This combination of drugs (EVG/COBI/FTC/TDF) developed and marketed by
      Gilead Sciences Inc. (Foster City, CA, USA) as STRIBILD((r)), is the first
      integrase inhibitor-based single-tablet regimen administered once-daily. In the
      USA, it has been approved for use in antiretroviral treatment-naive HIV-1
      patients with estimated creatinine clearance of >70 mL/min. The Department of
      Health and Human Services has approved EVG/COBI/FTC/TDF as one of preferred first
      line regimens for HIV-1 treatment. In Europe, the European Medicines Agency has
      approved STRIBILD in treatment-naive patients as well as in patients having no
      resistant mutation to any of the antiviral agents contained in STRIBILD. Its
      availability as a fixed-dose combination and once-daily dosage makes the
      adherence highly likely. However, it also discounts the possibility of dosage
      adjustment if needed. 

PMID- 24876795
TI  - Pertuzumab in human epidermal growth-factor receptor 2-positive breast cancer:
      clinical and economic considerations.
AB  - In the absence of specific therapy, the 15%-20% of breast cancers demonstrating
      human epidermal growth-factor receptor 2 (HER2) protein overexpression and/or
      gene amplification are characterized by a more aggressive phenotype and poorer
      prognosis compared to their HER2-negative counterparts. Trastuzumab (Herceptin),
      the first anti-HER2-targeted therapy, has been associated with improved survival
      outcomes in HER2-positive breast cancer. However, many patients with early stage
      disease continue to relapse, and metastatic disease remains incurable. In order
      to further improve these outcomes, several novel HER2-targeted agents have
      recently been developed. Pertuzumab (Perjeta), a monoclonal antibody against the
      HER2 dimerization domain, has also been associated with improved patient outcomes
      in clinical trials, and has recently been approved in combination with
      chemotherapy and trastuzumab for neoadjuvant therapy of early stage, HER2
      positive breast cancer and first-line treatment of metastatic disease. This
      review briefly summarizes pertuzumab's clinical development as well as the
      published evidence supporting its use, and highlights some of the currently
      unanswered questions that will influence pertuzumab's incorporation into clinical
      practice. 

PMID- 24876796
TI  - A proposed framework to improve the safety of medical devices in a Canadian
      hospital context.
AB  - PURPOSE: Medical devices are used to monitor, replace, or modify anatomy or
      physiological processes. They are important health care innovations that enable
      effective treatment using less invasive techniques, and they improve health care
      delivery and patient outcomes. Devices can also introduce risk of harm to
      patients. Our objective was to propose a surveillance system framework to improve
      the safety associated with the use of medical devices in a hospital. MATERIALS
      AND METHODS: The proposed medical device surveillance system incorporates
      multiple components to accurately document and assess the appropriate actions to
      reduce the risk of incidents, adverse events, and patient harm. The assumptions
      on which the framework is based are highlighted. The surveillance system was
      designed from the perspective of a tertiary teaching hospital that includes
      dedicated hospital staff whose mandate is to provide safe patient care to
      inpatients and outpatients and biomedical engineering services. RESULTS: The main
      components of the surveillance system would include an adverse medical device
      events database, a medical device/equipment library, education and training, and
      an open communication and feedback strategy. Close linkages among these
      components and with external medical device/equipment networks to the hospital
      must be established and maintained. A feedback mechanism on medical device
      related incidents, as well as implementation and evaluation strategies for the
      surveillance system are described to ensure a seamless transition and a high
      satisfactory level among the hospital staff. The direct cost items of the
      proposed surveillance system for consideration, and its potential benefits are
      outlined. CONCLUSION: The effectiveness of the proposed medical device
      surveillance system framework can be measured after it has been implemented in a
      Canadian hospital facility.

PMID- 24876797
TI  - A proposal for including nomophobia in the new DSM-V.
AB  - The Diagnostic and Statistical Manual of Mental Disorders (DSM) is considered to
      be the gold standard manual for assessing the psychiatric diseases and is
      currently in its fourth version (DSM-IV), while a fifth (DSM-V) has just been
      released in May 2013. The DSM-V Anxiety Work Group has put forward
      recommendations to modify the criteria for diagnosing specific phobias. In this
      manuscript, we propose to consider the inclusion of nomophobia in the DSM-V, and
      we make a comprehensive overview of the existing literature, discussing the
      clinical relevance of this pathology, its epidemiological features, the available
      psychometric scales, and the proposed treatment. Even though nomophobia has not
      been included in the DSM-V, much more attention is paid to the psychopathological
      effects of the new media, and the interest in this topic will increase in the
      near future, together with the attention and caution not to hypercodify as
      pathological normal behaviors. 

PMID- 24876798
TI  - Maximizing the benefit of health workforce secondment in Botswana: an approach
      for strengthening health systems in resource-limited settings.
AB  - To address health systems challenges in limited-resource settings, global health
      initiatives, particularly the President's Emergency Plan for AIDS Relief, have
      seconded health workers to the public sector. Implementation considerations for
      secondment as a health workforce development strategy are not well documented.
      The purpose of this article is to present outcomes, best practices, and lessons
      learned from a President's Emergency Plan for AIDS Relief-funded secondment
      program in Botswana. Outcomes are documented across four World Health
      Organization health systems' building blocks. Best practices include
      documentation of joint stakeholder expectations, collaborative recruitment, and
      early identification of counterparts. Lessons learned include inadequate
      ownership, a two-tier employment system, and ill-defined position duration. These
      findings can inform program and policy development to maximize the benefit of
      health workforce secondment. Secondment requires substantial investment, and
      emphasis should be placed on high-level technical positions responsible for
      building systems, developing health workers, and strengthening government to
      translate policy into programs. 

PMID- 24876800
TI  - Associations of teacher credibility and teacher affinity with learning outcomes
      in health classrooms.
AB  - In the present study (N = 633), we examine the role of teacher credibility and
      teacher affinity in classrooms. We explore the relations among these two
      characteristics and student gains in knowledge and valuing of learning about HIV
      and pregnancy prevention across high school classrooms. Results marshaled support
      for the notion that teacher characteristics are associated with classroom-level
      gains in learning outcomes. Above and beyond student-level predictors, teacher
      credibility (aggregated to the classroom level) was positively related to
      increases in knowledge across classrooms, whereas aggregated teacher affinity was
      positively related to an increased valuing of learning about HIV and pregnancy
      prevention across classrooms. Future directions and implications for practice are
      discussed.

PMID- 24876801
TI  - Medics and Marine Mammals - An Unlikely but Important Connection for Humanity's
      Survival.
AB  - Marine mammals, as top predators in the marine food web, are sentinels of changes
      in the oceans and public health. Pollution in the sea and overfishing of seafood
      resources affects these organisms just as much as it affects human beings.
      Medics, especially doctors, have an influential reach to patients, and are in an
      ideal position to get better acquainted with ongoing marine environmental issues
      and subsequently disseminating such information to them. While seemingly an out
      of-the-box approach, it is one that can help with environmental conservation and
      preservation for the future of humanity. 

PMID- 24876799
TI  - Empathy levels among first year Malaysian medical students: an observational
      study.
AB  - BACKGROUND: The literature indicates that medical practitioners experience
      declining empathy levels in clinical practice. This highlights the need to
      educate medical students about empathy as an attribute early in the academic
      curriculum. The objective of this study was to evaluate year one students' self
      reported empathy levels following a 2-hour empathy workshop at a large medical
      school in Malaysia. METHODS: Changes in empathy scores were examined using a
      paired repeated-measures t-test in this prospective before and after study.
      RESULTS: Analyzing the matched data, there was a statistically significant
      difference and moderate effect size between mean empathy scores before and 5
      weeks after the workshop (112.08+/-10.67 versus 117.93+/-13.13, P<0.0001, d=0.48)
      using the Jefferson Scale Physician Empathy (Student Version). CONCLUSION: The
      results of this observational study indicate improved mean self-reported empathy
      scores following an empathy workshop.

PMID- 24876803
TI  - Investigating the effects of imputation methods for modelling gene networks using
      a dynamic bayesian network from gene expression data.
AB  - BACKGROUND: Gene expression data often contain missing expression values.
      Therefore, several imputation methods have been applied to solve the missing
      values, which include k-nearest neighbour (kNN), local least squares (LLS), and
      Bayesian principal component analysis (BPCA). However, the effects of these
      imputation methods on the modelling of gene regulatory networks from gene
      expression data have rarely been investigated and analysed using a dynamic
      Bayesian network (DBN). METHODS: In the present study, we separately imputed
      datasets of the Escherichia coli S.O.S. DNA repair pathway and the Saccharomyces
      cerevisiae cell cycle pathway with kNN, LLS, and BPCA, and subsequently used
      these to generate gene regulatory networks (GRNs) using a discrete DBN. We made
      comparisons on the basis of previous studies in order to select the gene network
      with the least error. RESULTS: We found that BPCA and LLS performed better on
      larger networks (based on the S. cerevisiae dataset), whereas kNN performed
      better on smaller networks (based on the E. coli dataset). CONCLUSION: The
      results suggest that the performance of each imputation method is dependent on
      the size of the dataset, and this subsequently affects the modelling of the
      resultant GRNs using a DBN. In addition, on the basis of these results, a DBN has
      the capacity to discover potential edges, as well as display interactions,
      between genes.

PMID- 24876802
TI  - Intra-articular and Peri-articular Tumours and Tumour Mimics- What a Clinician
      and Onco-imaging Radiologist Should Know.
AB  - Definitive determination of the cause of articular swelling may be difficult
      based on just the clinical symptoms, physical examinations and laboratory tests.
      Joint disorders fall under the realms of rheumatology and general orthopaedics;
      however, patients with joint conditions manifesting primarily as intra-articular
      and peri-articular soft tissue swelling may at times be referred to an
      orthopaedic oncology department with suspicion of a tumour. In such a situation,
      an onco-radiologist needs to think beyond the usual neoplastic lesions and
      consider the diagnoses of various non-neoplastic arthritic conditions that may be
      clinically masquerading as masses. Differential diagnoses of articular lesions
      include infectious and non-infectious synovial proliferative processes,
      degenerative lesions, deposition diseases, vascular malformations, benign and
      malignant neoplasms and additional miscellaneous conditions. Many of these
      diseases have specific imaging findings. Knowledge of these radiological
      characteristics in an appropriate clinical context will allow for a more
      confident diagnosis. 

PMID- 24876804
TI  - Correlation between Degree of Radiologic Signs of Osteoarthritis and Functional
      Status in Patients with Chronic Mechanical Low Back Pain.
AB  - BACKGROUND: Osteoarthritis is the most intervening factors in producing
      mechanical low back pain (LBP). We aimed to evaluate the correlation between
      radiologic signs of osteoarthritis and functional status in patients with chronic
      mechanical LBP. METHODS: Severity of osteoarthritis and disability were evaluated
      with Kellgren and Lawrence Grading Scale (K&L) by simple lumbar X-ray and
      Oswestry Disability Questionnaire (ODQ) respectively. RESULTS: Although there was
      no significant correlation between ODQ and K&L score in general, the correlation
      was seen in female group (P = 0.024, r = 0.207). CONCLUSION: Mechanical LBP
      provides more disability in females suffering from more advanced osteoarthritis.

PMID- 24876805
TI  - A preliminary assessment of asymptomatic bacteriuria of pregnancy in brunei
      darussalam.
AB  - BACKGROUND: Asymptomatic bacteriuria describes a condition in which urine culture
      reveals a significant growth of pathogenic bacteria, specifically greater than
      10(5) of colony-forming units per millilitre of urine. It has a direct bearing on
      the health of a pregnant woman, her pregnancy and consequently the foetus. Thus,
      this study investigated the prevalence of asymptomatic bacteriuria of pregnancy
      in Raja Isteri Pengiran Anak Saleha (RIPAS) Hospital, the premiere tertiary
      hospital in Brunei Darussalam. METHODS: A total of 170 pregnant women who were
      visiting the Department of Obstetrics and Gynaecology at RIPAS Hospital for
      routine antenatal care between February and March 2011 volunteered for this cross
      sectional study. They did not present with any clinical symptoms of bacteriuria
      or indeed any other illness. They were investigated for bacteriuria by urine
      microscopy, culture, and sensitivity. RESULTS: Urine samples from seven of the
      women produced significant bacterial growth, showing a prevalence of 4.1%. The
      organisms isolated were Klebsiella species (2.94%) and Escherichia coli (1.18%);
      these bacteria were both sensitive to amoxicillin, vancomycin, tetracycline, and
      erythromycin. CONCLUSION: Brunei has a similar prevalence of asymptomatic
      bacteriuria to other South-East Asian countries.

PMID- 24876806
TI  - Influence of Age, Weight, and Pirani Score on the Number of Castings in the Early
      Phase of Clubfoot Treatment using Ponseti Method.
AB  - BACKGROUND: The objectives of this study were to investigate whether severity of
      clubfoot, age, and weight of the patients at initial manipulation and casting
      influence the total number of castings required. METHODS: This prospective study
      was conducted on 38 idiopathic clubfoot patients undergoing weekly manipulation
      and casting using the method recommended by Ponseti. The patients' age, weight,
      and foot Pirani score at the start of manipulation and casting were analysed
      against the total number of castings required to achieve correction to 60 degrees
      abduction. RESULTS: Simple linear regression analysis on the influence of
      weight, age, and Pirani score at the time of cast initiation showed that the
      Pirani score was the only significant predictor for the total number of castings
      required. CONCLUSION: The total number of castings required to treat clubfoot was
      determined by the severity of clubfoot but not by the weight and age of patients.

PMID- 24876807
TI  - The Effect of Second-Hand Smoke Exposure during Pregnancy on the Newborn Weight
      in Malaysia.
AB  - BACKGROUND: There was strong evidence from studies conducted in developed
      countries that second-hand smoke (SHS) exposure is detrimental to the birth
      weight of newborn. This study was conducted to determine the effect of exposure
      to SHS smoke during pregnancy on the weight of newborns. METHODS: A retrospective
      cohort study was conducted. The exposed group consists of 209 postnatal women who
      experienced SHS exposure at home because of a husband or other housemate who
      smoked inside the house throughout the pregnancy. The non-exposed group included
      211 women who did not experience SHS exposure at home or at work during
      pregnancy. We excluded non-Malay ethnicity, multiple births, and congenital
      defects. RESULTS: There was a significant difference in the adjusted mean birth
      weight between exposed infants [2893.0 g (95% confidence interval (CI): 2781.3,
      3004.7)] and not exposed infants to SHS [3046.1 g (95% CI 2929.5, 3162.6) (P <
      0.001)] after controlling for significant maternal factors. There was a 12.9 g
      (95% CI: 7.01, 18.96) reduction in birth weight for a corresponding increase in
      the exposure to the smoke of one cigarette (P < 0.001). The incidence of low
      birth weight (LBW) was higher in exposed women, [10% (95% CI: 5.94, 14.06)]
      compared to non-exposed women [4.7% (95% CI: 1.85, 7.55)]. CONCLUSION: This study
      found a significant association between SHS exposure during pregnancy and
      decreased birth weight.

PMID- 24876808
TI  - The implementation of teleneurosurgery in the management of referrals to a
      neurosurgical department in hospital sultanah amninah johor bahru.
AB  - BACKGROUND: Telemedicine in neurosurgery or teleneurosurgery has been widely used
      for transmission of clinical data and images throughout the country since its
      implementation in 2006. The impact is a reduction of patient number that need to
      be reviewed in the level III hospitals and an increment in the number of patients
      that are kept in level II hospitals for observation by the primary team. This
      translates to reduction of unnecessary transfer of patients and subsequently cost
      benefits for patients and medical providers. The main aim is to determine the
      amount of reduction in unnecessary transfer by the implementation of
      teleneurosurgery in the management of referrals to neurosurgical department in
      Hospital Sultanah Amninah Johor Bahru (HSAJB). Other factors associated with
      transfer decision are also evaluated. METHODS: This prospective cohort study was
      conducted in HSAJB, Johor over four months. A total of 349 subjects referred to
      HSAJB are included with 12 subjects excluded. The subjects are followed up from
      the time of referral until three months post-referrals. Related data includes the
      decision before and after reviewing the radiological images on teleconsultation
      website with clinical data available. RESULTS: There was a significant reduction
      in the number of inter-hospital transfer. 37% of transfer is avoided and patients
      are best kept in their original hospitals. However, there are additional findings
      in which there are 20.1% of patients that thought does not require transfer based
      on clinical data alone, would have to be transferred when the clinical data and
      images are reviewed. This translates to an increment of 20.1% need to be observed
      in neurosurgical center. Without the images, these patients might be observed in
      the referral hospitals with higher risk of deterioration. Other factors that are
      related to transfer decision apart from images include Glasgow Coma Scale (GCS)
      and diagnosis. The GCS significantly associated with transfer when only clinical
      data is reviewed. However, in situation where clinical data and images are
      reviewed together, the GCS and diagnosis are significantly associated with
      transfer decision. On multi-factorial analysis, more of mild head injury being
      transferred for observation in neurosurgical unit after images and clinical data
      reviewed which correlates to an increment from 1.85% to 3.9%. Another finding is
      reduced of risk of patients transferred for trauma from 1.85% to 0.519% after the
      data reviewed. CONCLUSION: Teleneurosurgery is beneficial in the management of
      referrals from level II hospitals. The inter-hospital transfer is significantly
      reduced, however there is an increased in the number of patients that need to be
      observed in neurosurgery unit for the risk of potential deterioration.

PMID- 24876810
TI  - Amoebic colitis presenting as ileocaecal intussusception - a rare case.
AB  - Ileocaecal intussusception is a common cause of acute intestinal obstruction
      presenting as a surgical emergency. We report a case of amoebic colitis in a 62
      years old man complaining of acute colicky pain in the right iliac fossa,
      associated with a three-day history of constipation but no other gastrointestinal
      tract symptoms. There was rebound tenderness on palpation of the right iliac
      fossa. Ultrasound scans revealed free fluid and a loop within a loop image in
      this area. At laparotomy, we discovered an Ileocaecal intussusception associated
      with a gangrenous caecum. A right hemicolectomy was performed with satisfactory
      outcome. The final diagnosis of amoebic colitis was obtained post-operatively
      using serology and pathology. This rare aetiology must be considered in patients
      with acute pain in the right iliac fossa in the tropical regions. Tropical
      surgeons must be aware of this scenario before they label a case of
      intussusception as idiopathic. The identification and treatment of invasive
      amoebic infection may reduce the recurrence of idiopathic intussusception. 

PMID- 24876809
TI  - Present status and future concerns of expanded newborn screening in malaysia:
      sustainability, challenges and perspectives.
AB  - Newborn screening (NBS) program is an important tool for the early diagnosis and
      preventive treatment of life-long impairments. NBS is one of the strategies
      recommended by the World Health Organization to promote the primary prevention of
      congenital anomalies and the health of children with these conditions. However,
      NBS initiation and implementation in developing countries, especially South-East
      Asian and North African regions, are slow and challenging. Expanded NBS is not
      mandatory and has not yet been incorporated into the public healthcare system in
      our country. Limited funding, manpower shortages, inadequate support services,
      low public awareness, and uncertain commitment from healthcare practitioners are
      the main challenges in establishing this program at the national level.
      Involvement and support from policy makers are very important to the success of
      the program and the benefit of the entire population. 

PMID- 24876811
TI  - Henoch-schonlein purpura associated with gangrenous appendicitis: a case report.
AB  - Henoch-Schonlein Purpura (HSP) is a leucocytoclastic vasculitis of unclear
      aetiology characterised by symmetrical, non-traumatic, nonthrombocytopenic
      purpura mostly involving the lower limbs and buttocks, as well as arthritis,
      gastrointestinal manifestations, and occasional nephritis. A 35 years old male
      presented with purpuric rash on the lower extremities, abdominal pain, fever,
      arthralgia, and melaena. A diagnosis of HSP with appendicitis was made, which is
      an exceedingly rare phenomenon. 

PMID- 24876812
TI  - Giant vascular hamartoma of the tongue.
AB  - We present one of the largest lingual hamartomas of the tongue base to have been
      reported, along with a review of the current literature and a description of the
      management of this case, as well as insights into the histopathology of the
      lesion. A 21-year-old woman presented with a mass on the base of her tongue,
      extending to the vallecula. The mass was found to be over 4 cm and enhancing on
      computed tomography. The size, vascularity, and site of the lesion merited its
      excision using the suprahyoid pharyngotomy approach. Histopathology confirmed the
      mass to be a vascular hamartoma. In reviewing the literature, we encountered 61
      reported cases of lingual hamartomas, which are described with a number of
      pathological variants and sites of occurrence and with different methods of
      surgical excision. The size, vascularity, and site of the lesion we found merited
      a different approach from the conventional transoral approach that was used in
      all of the previous reports. Also, our study agrees with current world literature
      that histopathological examination plays an important role in the final
      diagnosis. 

PMID- 24876813
TI  - Stroke thrombolysis at 5.5 hours based on computed tomography perfusion.
AB  - A young man was admitted with sudden onset of right-sided weakness. He was
      assessed in the emergency department, and an immediate computed tomography (CT)
      perfusion study of the brain was arranged, which showed a left middle cerebral
      artery territory infarct with occlusion of the M1 segment. There was a
      significant penumbra measuring approximately 50% of the arterial territory. By
      the time his assessment was completed, it was 5.5 hours from the onset of
      symptoms. He was nonetheless administered intravenous recombinant tissue
      plasminogen activator (rtPA) based on the significant penumbra. He was discharged
      from the hospital after one week with significant residual deficit. At 2 months
      clinic follow-up, he showed almost complete recovery with a Modified Rankin Score
      of 1. We hope to demonstrate that a significant penumbra is an important
      determinant for good neurological recovery and outcome following stroke
      thrombolysis, even when patients present outside the 4.5 hours onset-to-treatment
      time window. 

PMID- 24876814
TI  - The diagnostics of colorectal cancer.
AB  - Colorectal cancer (CRC) is one of the most frequent human malignant neoplasms.
      CRC has an estimated incidence of more than 1,000,000 new cases annually
      worldwide. Approximately one out of three people who develop CRC dies from the
      disease. Furthermore, CRC often affects inhabitants of industrialized countries
      in comparison to less developed countries. Several markers of colon cancer,
      including CEA, CA-19-9, TPS, TAG-72 and lysosomal hydrolases, have been
      identified and are now being adopted in routine clinical practice. Increased
      values of these markers are often the first signal of recurrence or metastases,
      which is useful in prediction and prognosis of clinical outcome of patients with
      CRC. Determination of the activity of lysosomal exoglycosidases in body fluids
      may bring some hope of improving diagnosis of colorectal cancer. However, it has
      to be remembered that currently the most effective diagnostic method of CRC is
      endoscopy. 

PMID- 24876816
TI  - New drugs in multiple myeloma - role of carfilzomib and pomalidomide.
AB  - Carfilzomib (CFZ), an epoxyketone with specific chymotrypsin-like activity, is a
      second-generation proteasome inhibitor with significant activity in patients with
      relapsed and refractory multiple myeloma. On July 20, 2012, the US Food and Drug
      Administration approved CFZ to treat patients with multiple myeloma who have
      received at least two prior therapies including bortezomib (BORT) and an
      immunomodulatory agent and have demonstrated disease progression on or within 60
      days of completion of the last therapy. Cytogenetic abnormalities did not appear
      to have a significant impact on the CFZ activity. Carfilzomib was well tolerated
      and demonstrated promising efficacy in patients with renal insufficiency.
      Pomalidomide (POM) (CC-4047) is a novel immunomodulatory derivative (IMID) with a
      stronger in vitro anti-myeloma effect compared with "older" IMIDs - thalidomide
      and lenalidomide (LEN). On February 8, 2013, the US Food and Drug Administration
      approved POM (Pomalyst, Celgene) for the treatment of MM patients who have
      received at least two prior therapies including LEN and BORT and have
      demonstrated progression on or within 60 days of completion of the last therapy.
      Pomalidomide is a novel IMID with significant anti-myeloma activity and
      manageable toxicity. This compound has shown high efficacy in MM patients who
      were resistant to prior use of LEN/BORT as well as in patients with a high-risk
      cytogenetic profile. Carfilzomib and POM have very high efficacy and will be used
      also in first line therapy in future. 

PMID- 24876815
TI  - Genetic and immune factors underlying the efficacy of cetuximab and panitumumab
      in the treatment of patients with metastatic colorectal cancer.
AB  - Efficacy of monoclonal anti-EGFR antibodies (cetuximab, panitumumab) used in
      combination with chemotherapy or alone has been demonstrated in clinical trials
      of patients with mCRC. Both drugs block signaling EGFR pathway in malignant cells
      (blocking ligand binding and EGFR dimerization). Obtaining treatment responses
      with anti-EGFR agents is possible only in a selected subgroup of patients with
      mCRC. Successful treatment with cetuximab and panitumab is possible almost
      exclusively in patients without RAS mutations. Research on predictive value of
      EGFR gene copy number, PI3KCA gene mutations, P53 and PTEN, and EGFR their
      ligands concentrations is ongoing. Cetuximab, as IgG1 class antibody, can cause
      antibody dependent cellular cytotoxicity against neoplasm cells, while
      panitumumab, as IgG2 class antibody, does not induce such effect. Therefore a
      potential predictor cetuximab therapy may be the presence of different
      polymorphic forms of the genes for receptor immunoglobulin Fc fragments:
      FcgammaRIIa and FcgammaRIII subclasses. 

PMID- 24876817
TI  - Comparison of 4-hydroxynonenal-induced p53-mediated apoptosis in prostate cancer
      cells LNCaP and DU145.
AB  - AIM OF THE STUDY: To explore the mechanism of oxidative stress in the development
      of prostate cancer, here we compared 4-hydroxynonenal (4-HNE)- treated LNCaP
      (hormone-sensitive) and DU145 (hormone insensitive) cells with significant
      differences in sensitivity to androgen. MATERIAL AND METHODS: The prostate cancer
      cell line LNCaP and late cell line DU145 were treated with different
      concentrations of 4-HNE. The cell proliferation, apoptosis and mitochondrial
      transmembrane potential were detected at different time points, and expression of
      related molecules in cell proliferation and apoptosis signal pathway was analyzed
      by Western blot, and the over-expression of glutathione S-transferase (GSTA-4)
      was used to validate the changes of the effects of 4-HNE on the two kinds of
      cells. RESULTS: LNCaP cells showed greater antiproliferative and proapoptotic
      activities of HNE in a time- and dose-dependent manner corresponding to the
      activation of p53-mediated intrinsic apoptotic signaling, but JNK activation was
      not observed. In contrast, HNE-treated DU145 cells showed less apoptosis and
      proliferation was not inhibited; instead there was sustained activation of JNK,
      but activation of p53, p-p53, p21, Bax and caspase-3 was not observed. In
      addition, their effect of induction of apoptosis can be inhibited by
      overexpression of GSTA-4. CONCLUSIONS: These studies suggest that 4-HNE promotes
      prostate cancer cell apoptosis through the p53 signaling pathway; the differences
      of sensitivity to 4-HNE in LNCaP and DU145 cells may be related to the androgen
      sensitivity of prostate cancer cells; and the 4-HNE-induced p53-mediated
      apoptosis signal is regulated by GSTA-4.

PMID- 24876818
TI  - Possible role of CD22, CD79b and CD20 expression in distinguishing small
      lymphocytic lymphoma from chronic lymphocytic leukemia.
AB  - AIM OF THE STUDY: Flow cytometry has an important role in diagnosis and
      classification of B-cell lymphoproliferative disorders (BCLPDs). However, in
      distinguishing chronic lymphocytic leukemia (CLL) from small lymphocytic lymphoma
      (SLL) only clinical criteria are available so far. Aim of the study was to
      determine differences in the expression of common B cell markers (CD22, CD79b and
      CD20) on the malignant lymphocytes in the peripheral blood samples of CLL and SLL
      patients. MATERIAL AND METHODS: Peripheral blood samples of 56 CLL and 11 SLL
      patients were analyzed by 5-color flow cytometry on the CD45/CD19/CD5 gate for
      CD22, CD79b and CD20. RESULTS: In the samples collected from the CLL patients,
      CD22 expression was detected in only 20% of patients in the low pattern, while in
      SLL patients the expression was medium and present in 90.9% of patients (p <
      0.0001). For CD79b expression, statistical significance is reached both in the
      expression pattern, which was low/medium for CLL and high for SLL, and expression
      level (p = 0.006). The expression of CD20 was counted as the CD20/CD19 ratio. The
      average ratio was 0.512 in the CLL patients vs. 0.931 in the SLL patients (p =
      0.0001). CONCLUSIONS: The pattern of expression and expression level of CD22,
      CD79b and CD20 in peripheral blood could be used for distinguishing SLL from CLL
      patients.

PMID- 24876819
TI  - Lack of prognostic significance of adiponectin immunohistochemical expression in
      patients with triple-negative breast cancer.
AB  - INTRODUCTION: Triple-negative breast cancers (TNBCs) - which lack the expression
      of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth
      factor receptor 2 (HER-2) - have no established markers that can be used for
      prognostic stratification. As adiponectin has been previously implicated in a
      more aggressive phenotype of primary breast cancer, we explored the relation
      between adiponectin immunohistochemical expression and prognosis in TNBCs.
      MATERIAL AND METHODS: Immunohistochemical staining for adiponectin was performed
      in 38 TNBC patients. Disease-free survival (DFS) and overall survival (OS) served
      as the main outcome measures. RESULTS: Of the 38 TNBC patients, 18 (47%) had
      negative and 20 (53%) positive adiponectin immunohistochemical expression. We did
      not find any significant association between adiponectin immunohistochemical
      expression and the baseline characteristics. In addition, there were no
      associations between adiponectin immunohistochemical expression and prognosis.
      CONCLUSIONS: Although our results suggest that adiponectin immunohistochemical
      expression is not of prognostic significance in TNBCs, further studies are
      warranted to determine the role of this adipokine in breast cancer biology.

PMID- 24876820
TI  - The efficacy and safety of thalidomide-based therapy in patients with advanced
      non-small cell lung cancer: a meta-analysis.
AB  - Several randomized controlled clinical trials have compared therapy with or
      without thalidomide in the treatment of advanced non-small cell lung cancer
      (NSCLC). However, these studies did not produce consistent results. We carried
      out a meta-analysis to determine the efficacy and safety of thalidomide-based
      therapy in patients with advanced NSCLC. For this meta-analysis, we selected
      randomized clinical trials that compared thalidomide in combination with other
      therapy or other therapy alone in patients with advanced NSCLC. The outcomes
      included median overall survival (OS), one- and two-year survival, tumor
      response, and toxicities. Hazard ratios (HRs) or risk ratios (RRs) were reported
      with 95% confidence intervals (CIs). A total of 5 eligible trials were included
      for the meta-analysis, with 729 patients in the thalidomide group and 711
      patients in the control group. Compared with non-thalidomide-based therapy,
      patients receiving thalidomide plus other therapy did not differ significantly in
      terms of one- and two-year survival or tumor response (RR = 1.32, 95% CI: 0.66
      2.63, p = 0.43; RR = 1.22, 95% CI: 0.48-3.11, p = 0.68; RR = 1.05, 95% CI: 0.92
      1.19, p = 0.51, respectively). However, thalidomide-based therapy induced more
      grade 3-4 dizziness and constipation (RR = 2.05, 95% CI: 1.10-3.81, p = 0.02; RR
      = 4.78, 95% CI: 1.84-12.38, p = 0.001, respectively). The addition of thalidomide
      to other therapy did not improve survival and tumor response in patients with
      advanced NSCLC, and thalidomide-based therapy was associated with more grade 3/4
      dizziness and constipation. 

PMID- 24876822
TI  - Serrated polyps detected during screening colonoscopies.
AB  - AIM OF THE STUDY: It is estimated that between 15% and 35% of sporadic colorectal
      cancers (CRC) developing from adenomas come from serrated polyps. Currently, the
      most effective method used to prevent CRC is the removal of adenomas, including
      serrated polyps, during colonoscopy. The aim of this paper is to analyze the
      changes characterized as serrated polyps and detected during screening
      colonoscopies performed as part of the Screening Program for Early Colorectal
      Cancer Detection (SPED). MATERIAL AND METHODS: In our center, as part of the
      nationwide SPED between 2000 and 2009, 1,442 screening colonoscopies were
      performed. RESULTS: Serrated polyps were found in 11.9% of all patients and in
      45.8% of patients who had polyps removed by endoscopy. In screening colonoscopy
      of the large intestine, the following polyps were found most frequently:
      hyperplastic, < 1 cm, without a stalk, multiple, located in the distal part of
      the large intestine, in men and in patients with a first-degree relative with a
      history of abdominal cancer. Detecting and removing polyps was facilitated by the
      fact that the cecum was intubated and the bowel preparation had been performed
      either very well or well. The detection rate of serrated polyps was not
      influenced by patients' place of residence or their age. CONCLUSIONS: Serrated
      polyps constitute a frequent, and very frequent among removed polyps, abnormality
      detected during screening colonoscopy.

PMID- 24876821
TI  - Outcome of refractory and relapsed acute myeloid leukemia in children treated
      during 2005-2011 - experience of the Polish Pediatric Leukemia/Lymphoma Study
      Group (PPLLSG).
AB  - AIM OF THE STUDY: Recent studies showed relatively better outcome for children
      with refractory (refAML) and relapsed acute myeloid leukemia (relAML). Treatment
      of these patients has not been unified within Polish Pediatric Leukemia/Lymphoma
      Study Group (PPLLSG) so far. The goal of this study is to analyze the results of
      this therapy performed between 2005-2011. MATERIAL AND METHODS: The outcome data
      of 16 patients with refAML and 62 with relAML were analyzed retrospectively.
      Reinduction was usually based on idarubicine, fludarabine and cytarabine with
      allogenic hematopoietic stem cell transplant (alloHSCT) in 5 refAML and 30 relAML
      children. RESULTS: Seventy seven percent relAML patients entered second complete
      remission (CR2). Five-year OS and disease-free survival (DFS) were estimated at
      16% and 30%. The outcome for patients after alloHSCT in CR2 (63%) was better than
      that of those not transplanted (36%) with 5-year OS of 34% vs. 2-year of 7% and 5
      year DFS of 40% vs. 12.5%. Second complete remission achievement and alloHSCT
      were the most significant predictors of better prognosis (p = 0.000 and p =
      0.024). The outcome of refAML children was significantly worse than relAML with
      first remission (CR1) rate of 33%, OS and DFS of 25% at 3 years and 53% at 2
      years, respectively. All survivors of refAML were treated with alloHSCT after
      CR1. CONCLUSIONS: The uniform reinduction regimen of the documented efficacy and
      subsequent alloHSCT in remission is needed to improve the outcome for ref/relAML
      children treated within PPLLSG. The focus should be on the future risk-directed
      both front and second line AML therapy.

PMID- 24876823
TI  - A meta-analysis of treatment of vestibular schwannoma using Gamma Knife
      radiosurgery.
AB  - AIM OF THE STUDY: One of the alternative methods of surgical treatment of
      vestibular schwannoma is Gamma Knife radiosurgery. The purpose of this
      metaanalysis was to analyze the progress in treatment of vestibular schwannoma
      using Gamma Knife radiosurgery based on data in the literature of the last five
      years. MATERIAL AND METHODS: In the collected English-language literature from
      the years 2007-2011, contained in 20 scientific journals, clinical articles of
      many years study at a single center were extracted and also review papers and
      case reports. The main criteria of our own analysis were: patient age, tumor
      size, the dose in Gy, the time from surgery to follow-up, the degree of tumor
      growth inhibition, and hearing preservation. For statistical calculations
      comparing series of studies we used nonparametric analysis of variance and tests
      at the significance level of p > 0.05. RESULTS: The 46 evaluated clinical
      articles show the results of studies over many years. A comparison of the results
      of the analysis made on the basis of papers published in the period 1998-2007
      with the results of the current series from the period 2007-2011 allowed us to
      establish that the average dose applied to the periphery of the tumor was lower
      (12.4 Gy) than in the earlier series of 1998-2007 (14.2 Gy), and hearing
      preservation was higher (66.45% vs. 51.0%). CONCLUSIONS: Clinical findings widely
      documented in the literature over the past five years indicate the progress in
      treatment of vestibular schwannoma using Gamma Knife radiosurgery.

PMID- 24876824
TI  - Spontaneous hematological remission of acute myeloid leukemia.
AB  - Spontaneous remission (SR) of acute myeloid leukemia (AML) in adults is observed
      very rarely. To date, about 100 cases have been presented in the literature. To
      our best knowledge, we describe the first adult Polish patient suffering from
      acute myelomonocytic leukemia (48, XY, +13, +21/46, XY), in whom after supportive
      therapy, including non-irradiated, non-leukocyte depleted red cell transfusions
      and low-dose corticosteroid, we observed resolution of the disease without
      cytogenetic remission. We suggest a potential transfusion-associated graft versus
      host-diseases (TA-GVHD) and graft-versus leukemia (GVL) reaction which might lead
      to spontaneous hematological remission. However, we did not observe clinical
      symptoms of such reactions apart from a short episode of non-infectious diarrhea.
      Additionally, steroids were administered but their role in inducing SR, in our
      opinion, seems less probable. This 77-year-old man remained in SR for 7 months,
      when repeated analysis showed AML recurrence. He died due to septic shock 2.5
      months later. Additionally, we present a review of the literature. 

PMID- 24876825
TI  - Skin and maxillary sinus involvement of colon cancer.

PMID- 24876826
TI  - Cardiac rhabdomyosarcoma of the left atrium.

PMID- 24876827
TI  - Effect of Furin inhibitor on lung adenocarcinoma cell growth and metastasis.
AB  - BACKGROUND: To investigate the mechanisms of lung adenocarcinoma cell metastasis
      and provide a theoretical basis for the in-depth study of lung adenocarcinoma.
      METHODS: A549 cells are incubated with different concentrations of Furin
      inhibitor for indicated times. The proliferation and migration were confirmed
      with MTT, colony formation, wound Healing and Transwell assayes. Hochest 33342 /
      PI double staining was used to detect apoptosis. Cell migration and apoptosis
      associated proteins were analysed by enzyme-linked immunosorbent assay (ELISA)
      and western blot. RESULTS: We have found that Furin inhibitor play a significant
      role in inhibition A549 cell growth. And we also found cell migration was
      inhibited significantly upon Furin inhibitor treatment. CONCLUSION: The
      proliferration and migration of A549 cell were inhibited by Furin inbitor through
      down-regulation the expression of migration and apoptosis related proteins.

PMID- 24876828
TI  - Effects of dietary intervention in young female athletes with menstrual
      disorders.
AB  - BACKGROUND: The aim of this study was to evaluate the influence of three months
      of dietary intervention on menstrual cycle in young female athletes with
      amenorrhea or oligomenorrhea. METHODS: From forty-five female professional
      athletes with menstrual irregularity that were recruited thirty-one, aged 18.1 +/
      2.6 years, completed the study and were analyzed. Hyperprolactinemia, thyroid
      dysfunction, primary ovarian failure and hyperandrogenism were excluded in the
      study participants. The subjects started intense training at the age of 11.2 +/-
      3.5 years and continued during next 6.8 +/- 3.3 years. Energy and nutrients
      intake, total energy expenditure, energy availability and body composition as
      well as serum concentrations of LH, FSH, 17 - beta estradiol and progesterone
      were measured at the beginning of the study and after three months of
      individualized dietary intervention. RESULTS: Following three months of dietary
      intervention significant increase in energy intake (2354 +/- 539 vs. 258 8 +/-
      557 kcal, P = 0.004) and energy availability (28.3 +/- 9.2 vs. 35.8 +/- 12.3
      kcal/kg FFM/d, P = 0.011) was observed as well as improved energy balance (-288
      +/- 477 vs. -51 +/- 224 kcal/d, P = 0.002). Though no changes in BMI and body
      composition were noted but significant rise in LH concentrations (3.04 +/- 1.63
      vs. 4.59 +/- 2.53 mIU/ml, P = 0.009) and LH to FSH ratio (0.84 +/- 0.56 vs. 0.96
      +/- 0.52, P = 0.001) was achieved, but no restoration of menstrual cyclicity.
      CONCLUSIONS: This report provides further support for the role of energy
      deficiency in menstrual disorders among young female athletes and the benefits of
      an adequate energy intake and energy availability on hormones concentration.
      Continuation controlled dietary intervention is needed to assess the extent to
      which long-term improvement in the nutritional status results in improvements in
      the hormonal status of female athletes, to an extent that would allow the
      regulation of the menstrual cyclity.

PMID- 24876831
TI  - Case report on the illness of paul klee (1879-1940).
AB  - This article reports on the disease that afflicted Paul Klee, the famous artist.
      He died before the disease that killed him could be properly diagnosed. There was
      some conjecture afterwards that he may have suffered from scleroderma. The
      thorough and diligent research the author of this article has carried out over
      many years allows him to argue that Paul Klee was suffering from this autoimmune
      disease since 1935. With a degree of probability that borders on certainty, it
      seems that the artist suffered from 'diffuse systemic sclerosis', and it is from
      this, the most severe form of the rare autoimmune disease, that he died in 1940. 

PMID- 24876829
TI  - Type 2 Innate Lymphoid Cells in Allergic Disease.
AB  - Type II innate lymphoid cells (ILC2) are a novel population of lineage-negative
      cells that produce high levels of Th2 cytokines IL-5 and IL-13. ILC2 are found in
      human respiratory and gastrointestinal tissue as well as in skin. Studies from
      mouse models of asthma and atopic dermatitis suggest a role for ILC2 in promoting
      allergic inflammation. The epithelial cytokines IL-25, IL-33, and TSLP, as well
      as the lipid mediator leukotriene D4, have been shown to potently activate ILC2
      under specific conditions and supporting the notion that many separate pathways
      in allergic disease may result in stimulation of ILC2. Ongoing investigations are
      required to better characterize the relative contribution of ILC2 in allergic
      inflammation as well as mechanisms by which other cell types including
      conventional T cells regulate ILC2 survival, proliferation, and cytokine
      production. Importantly, therapeutic strategies to target ILC2 may reduce
      allergic inflammation in afflicted individuals. This review summarizes the
      development, surface marker profile, cytokine production, and upstream regulation
      of ILC2, and focuses on the role of ILC2 in common allergic diseases.

PMID- 24876830
TI  - Bladder Injury During Cesarean Delivery.
AB  - Cesarean section is the most common surgery performed in the United States with
      over 30% of deliveries occurring via this route. This number is likely to
      increase given decreasing rates of vaginal birth after cesarean section (VBAC)
      and primary cesarean delivery on maternal request, which carries the inherent
      risk for intraoperative complications. Urologic injury is the most common injury
      at the time of either obstetric or gynecologic surgery, with the bladder being
      the most frequent organ damaged. Risk factors for bladder injury during cesarean
      section include previous cesarean delivery, adhesions, emergent cesarean
      delivery, and cesarean section performed at the time of the second stage of
      labor. Fortunately, most bladder injuries are recognized at the time of surgery,
      which is important, as quick recognition and repair are associated with a
      significant reduction in patient mortality. Although cesarean delivery is a
      cornerstone of obstetrics, there is a paucity of data in the literature either
      supporting or refuting specific techniques that are performed today. There is
      evidence to support double-layer closure of the hysterotomy, the routine use of
      adhesive barriers, and performing a Pfannenstiel skin incision versus a vertical
      midline subumbilical incision to decrease the risk for bladder injury during
      cesarean section. There is also no evidence that supports the creation of a
      bladder flap, although routinely performed during cesarean section, as a method
      to reduce the risk of bladder injury. Finally, more research is needed to
      determine if indwelling catheterization, exteriorization of the uterus, and
      methods to extend hysterotomy incision lead to bladder injury.

PMID- 24876832
TI  - Malignant solitary fibrous kidney tumor with peritoneal disease: a case report.
AB  - We report a case of a large malignant solitary fibrous kidney tumor. A complete
      surgical resection of the primary tumor and peritoneal disease was carried out,
      and a histological examination confirmed the initial diagnosis. We describe and
      discuss the characteristics of this rare kidney neoplasm. 

PMID- 24876833
TI  - Response of Bone Resorption Markers to Aristolochia longa Intake by Algerian
      Breast Cancer Postmenopausal Women.
AB  - Aristolochia longa is widely used in traditional medicine in Algeria to treat
      breast cancer. The aim of the present study was to investigate the response of
      bone resorption markers to A. longa intake by Algerian breast cancer
      postmenopausal women. According to the A. longa intake, breast cancer patients
      were grouped into A. longa group (Al) (n = 54) and non-A. longa group (non-Al) (n
      = 24). 32 women constituted the control group. Bone resorption markers (from
      urine) pyridinoline (PYD) and deoxypyridinoline (DPD) were determined by HPLC.
      Serum and urinary creatinine, uric acid, and urea were measured. 1 g of A. longa
      intake resulted in significant rise of renal serum markers and a pronounced
      increase of bone resorption markers. The intake of A. longa roots is detrimental
      for kidney function and resulted in high bone resorption, maybe due to the
      reduction in renal function caused by the aristolochic acids contained in the
      roots. 

PMID- 24876834
TI  - Impact of benign prostatic hyperplasia pharmacological treatment on transrectal
      prostate biopsy adverse effects.
AB  - Background. Benign prostatic hyperplasia (BPH) pharmacological treatment may
      promote a decrease in prostate vascularization and bladder neck relaxation with
      theoretical improvement in prostate biopsy morbidity, though never explored in
      the literature. Methods. Among 242 consecutive unselected patients who underwent
      prostate biopsy, after excluding those with history of prostate biopsy/surgery or
      using medications not for BPH, we studied 190 patients. On the 15th day after
      procedure patients were questioned about symptoms lasting over a week and
      classified according to pharmacological BPH treatment. Results. Thirty-three
      patients (17%) were using alpha-blocker exclusively, five (3%) 5-alpha-reductase
      inhibitor exclusively, twelve (6%) patients used both medications, and 140 (74%)
      patients used none. There was no difference in regard to age among groups (P =
      0.5). Postbiopsy adverse effects occurred as follows: hematuria 96 (50%),
      hematospermia 53 (28%), hematochezia 22 (12%), urethrorrhagia 19 (10%), fever 5
      (3%), and pain 20 (10%). There was a significant negative correlation between
      postbiopsy hematuria and BPH pharmacological treatment with stronger correlation
      for combined use of 5-alpha-reductase inhibitor and alpha-blocker over 6 months
      (P = 0.0027). Conclusion. BPH pharmacological treatment, mainly combined for at
      least 6 months seems to protect against prostate biopsy adverse effects. Future
      studies are necessary to confirm our novel results. 

PMID- 24876835
TI  - Incidental prostate cancer in transurethral resection of the prostate specimens
      in the modern era.
AB  - Objectives. To identify rates of incidentally detected prostate cancer in
      patients undergoing surgical management of benign prostatic hyperplasia (BPH).
      Materials and Methods. A retrospective review was performed on all transurethral
      resections of the prostate (TURP) regardless of technique from 2006 to 2011 at a
      single tertiary care institution. 793 men (ages 45-90) were identified by
      pathology specimen. Those with a known diagnosis of prostate cancer prior to TURP
      were excluded (n = 22) from the analysis. Results. 760 patients had benign
      pathology; eleven (1.4%) patients were found to have prostate cancer. Grade of
      disease ranged from Gleason 3 + 3 = 6 to Gleason 3 + 4 = 7. Nine patients had
      cT1a disease and two had cT1b disease. Seven patients were managed by active
      surveillance with no further events, one patient underwent radiation, and three
      patients underwent radical prostatectomy. Conclusions. Our series demonstrates
      that 1.4% of patients were found to have prostate cancer, of these 0.5% required
      treatment. Given the low incidental prostate cancer detection rate, the value of
      pathologic review of TURP specimens may be limited depending on the patient
      population. 

PMID- 24876836
TI  - Geriatric Hip Fractures and Inpatient Services: Predicting Hospital Charges Using
      the ASA Score.
AB  - Purpose. To determine if the American Society of Anesthesiologist (ASA) score can
      be used to predict hospital charges for inpatient services. Materials and
      Methods. A retrospective chart review was conducted at a level I trauma center on
      547 patients over the age of 60 who presented with a hip fracture and required
      operative fixation. Hospital charges associated with inpatient and postoperative
      services were organized within six categories of care. Analysis of variance and a
      linear regression model were performed to compare preoperative ASA scores with
      charges and inpatient services. Results. Inpatient and postoperative charges and
      services were significantly associated with patients' ASA scores. Patients with
      an ASA score of 4 had the highest average inpatient charges of services of
      $15,555, compared to $10,923 for patients with an ASA score of 2. Patients with
      an ASA score of 4 had an average of 45.3 hospital services compared to 24.1 for
      patients with a score of 2. Conclusions. A patient's ASA score is associated with
      total and specific hospital charges related to inpatient services. The findings
      of this study will allow payers to identify the major cost drivers for inpatient
      services based on a hip fracture patient's preoperative physical status. 

PMID- 24876837
TI  - How good are simplified models for protein structure prediction?
AB  - Protein structure prediction (PSP) has been one of the most challenging problems
      in computational biology for several decades. The challenge is largely due to the
      complexity of the all-atomic details and the unknown nature of the energy
      function. Researchers have therefore used simplified energy models that consider
      interaction potentials only between the amino acid monomers in contact on
      discrete lattices. The restricted nature of the lattices and the energy models
      poses a twofold concern regarding the assessment of the models. Can a native or a
      very close structure be obtained when structures are mapped to lattices? Can the
      contact based energy models on discrete lattices guide the search towards the
      native structures? In this paper, we use the protein chain lattice fitting (PCLF)
      problem to address the first concern; we developed a constraint-based local
      search algorithm for the PCLF problem for cubic and face-centered cubic lattices
      and found very close lattice fits for the native structures. For the second
      concern, we use a number of techniques to sample the conformation space and find
      correlations between energy functions and root mean square deviation (RMSD)
      distance of the lattice-based structures with the native structures. Our analysis
      reveals weakness of several contact based energy models used that are popular in
      PSP. 

PMID- 24876838
TI  - Oxidative stress and inflammation in diabetic complications.

PMID- 24876839
TI  - Primary thyroid disorders in patients with endogenous hypercortisolism: an
      observational study.
AB  - Cushing's syndrome (CS) may alter the performance of the hypothalamic-hypophyseal
      thyroid axis. We searched for a relationship between hypercortisolism and primary
      thyroid disorders. The medical records of 40 patients with CS were
      retrospectively examined. Thyroid ultrasonography (USG), basal thyroid function
      test results (TFT), and antithyroglobulin and antithyroperoxidase antibodies were
      analyzed. In 80 control subjects, matched by age and gender with CS patients,
      thyroid USG, TFTs, and autoantibody panel were obtained. Among the CS patients,
      17 had nodular goiter, versus 24 controls (42.5% versus 30%, P > 0.05). Among the
      twenty-five patients with an available TFT and autoantibody panel-before and
      after surgical curative treatment-autoantibody positivity was detected in 2 (8%)
      patients before and 3 (12%) after surgery (P = 0.48). Regarding TFT results, 1
      (2.5%) patient had subclinical hyperthyroidism and 1 (2.5%) had subclinical
      hypothyroidism, whereas 1 (2.5%) control had hyperthyroidism. In total, 21
      (52.5%) patients and 32 (40%) controls had >=1 of the features of thyroid
      disorder, including goiter, positive thyroid autoantibody, and thyroid function
      abnormality; the difference was not significant (P > 0.05). The prevalence of
      primary thyroid disorders is not significantly increased in patients with CS. 

PMID- 24876840
TI  - Cancer in the elderly.

PMID- 24876841
TI  - Novel Gyroviruses, including Chicken Anaemia Virus, in Clinical and Chicken
      Samples from South Africa.
AB  - Introduction. Chicken anaemia virus, CAV, was until recently the only member of
      the Gyrovirus genus. 6 novel gyroviruses, AGV2, HGyV1, and GyV3-6, have since
      been discovered in human and chicken samples. Methods. PCR amplification of the
      VP2 gene was used to detect AGV2/HGyV1, GyV3, and CAV in a range of clinical
      samples including stool, respiratory, CSF, and HIV-positive plasma. Screening of
      fresh local chicken meat was also performed. Results. AGV2/HGyV1 or GyV3 was
      detected in stools from healthy children (17/49, 34.7%) and patients with
      diarrhoea (22/149, 14.8%). 1.2% (3/246) nasopharyngeal respiratory samples were
      positive. No AGV2/HGyV1 or GyV3 was detected in nasal swabs from wheezing
      patients, in CSF from patients with meningitis, and in HIVpositive plasma. CAV
      was found in 51% (25/49) of stools from healthy children and 16% (24/149) in
      diarrhoea samples. Screening of 28 chicken samples showed a higher prevalence of
      gyrovirus (20/28, 71%) compared to CAV (1/28, 3.6%). Phylogenetic analysis of the
      CAV VP1 gene showed South African sequences clustering with Brazilian isolates
      from genotypes D2 and A2. Conclusion. Novel gyroviruses, including CAV, are
      present in the South African population with diarrhoea and respiratory illness as
      well as in healthy children. Their presence suggests an origin from chicken meat
      consumption. 

PMID- 24876842
TI  - The Efficacy of Inositol and N-Acetyl Cysteine Administration (Ovaric HP) in
      Improving the Ovarian Function in Infertile Women with PCOS with or without
      Insulin Resistance.
AB  - Objective. Substances such as inositol and N-acetylcysteine (NAC) have been
      recently shown to be effective in treatment of PCOS patients. The aim of this
      prospective trial is to evaluate the efficacy of NAC + Inositol + folic acid on
      ovulation rate and menstrual regularity in PCOS patients with and without insulin
      resistance. Methods. Among the 91 PCOS patients treated with NAC + Inositol +
      folic, insulin resistance was present in 44 subjects (A) and absent in 47 (B).
      The primary endpoint was the ovulation rate/year, determined by menstrual diary,
      serum progesterone performed between 21 degrees  and 24 degrees  days, ultrasound
      findings of growth follicular or luteal cysts, and luteal ratio. HOMA-index
      assessment after 6 and 12 months of treatment was evaluated as secondary
      endpoint. Results. In both groups there was a significant increase in ovulation
      rate and no significant differences were found in the primary outcome between two
      groups. In group A, a significant reduction of HOMA-index was observed.
      Conclusions. The association NAC + Inositol + folic, regardless of insulin
      resistance state, seems to improve ovarian function in PCOS patients. Therefore,
      inositol and NAC may have additional noninsulin-related mechanisms of action that
      allow achieving benefits also in those patients with negative HOMA-index. 

PMID- 24876843
TI  - Extreme REM Rebound during Continuous Positive Airway Pressure Titration for
      Obstructive Sleep Apnea in a Depressed Patient.
AB  - A 20% increase in REM sleep duration has been proposed as a threshold to identify
      REM rebound in patients with obstructive sleep apnea (OSA) who start continuous
      positive airway pressure (CPAP) treatment. We describe the case of one patient
      with OSA who showed an unexpectedly high degree of REM rebound during titration
      of CPAP. A 34-year-old man was diagnosed with OSA. He remained untreated for many
      years, during which he developed systemic hypertension, depression, and severe
      daytime somnolence. When he was reevaluated sixteen years later, his Epworth
      sleepiness score was 18, and his OSA had greatly worsened (apnea/hypopnea index:
      47, lowest nocturnal saturation: 57%). He underwent a successful CPAP titration
      during nocturnal polysomnography. Electroencephalographic analysis of the sleep
      recording revealed a huge amount of REM sleep, accounting for 72% of the total
      sleep time. When asked, the patient referred that he had suddenly interrupted
      paroxetine assumption three days before the polysomnography. The very large REM
      rebound observed in this patient could be due to additional effects of initiation
      of CPAP therapy and suspension of antidepressive treatment. This case does not
      report any dangerous consequence, but sudden antidepressive withdrawal could be
      dangerous for patients with OSA who develop hypoventilation during REM sleep with
      CPAP application. 

PMID- 24876844
TI  - Valsalva retinopathy associated with sexual activity.
AB  - A 54-year-old healthy male presented complaining of sudden loss of vision in the
      right eye. Initial visual acuity was counting fingers. The patient's acute vision
      loss developed after sexual activity. Color fundus photos and fluorescein
      angiography were performed showing a large subinternal limiting membrane
      hemorrhage in the macular area. A 23-gauge sutureless pars plana vitrectomy with
      brilliant blue assisted internal limiting membrane peeling was performed with
      best-corrected visual acuity recovery to 20/50 at 6 months of followup. 

PMID- 24876845
TI  - Pars plana vitrectomy combined with focal endolaser photocoagulation for
      idiopathic macular telangiectasia.
AB  - Background. To report the outcome of pars plana vitrectomy (PPV) combined with
      intraoperative endolaser focal photocoagulation (PC) on eyes with idiopathic
      macular telangiectasis (MacTel) type 1. Methods. This was a retrospective study
      of two female patients with MacTel type 1 who were resistant to focal
      photocoagulation, sub-Tenon triamcinolone injection, and/or antiangiogenic drugs.
      The best-corrected visual acuity (BCVA) was determined, and fluorescein
      angiography (FA) and spectral domain optical coherence tomography (SD-OCT) were
      performed before and after surgery for up to 19 months. Results. After surgery,
      the BCVA gradually improved from 20/100 to 20/20 at 19 months in Case 1 and from
      20/50 to 20/13 at 13 months in Case 2. Fluorescein angiography (FA) showed
      leakage at the late phase, and OCT showed that the cystoid macular edema was
      resolved and the fovea was considerably thinner postoperatively. Conclusion.
      Patients with MacTel type 1 who are refractory to the other types of treatments
      can benefit from PPV combined with intraoperative endolaser focal PC with
      functional and morphological improvements. 

PMID- 24876847
TI  - Enhanced adipogenicity of bone marrow mesenchymal stem cells in aplastic anemia.
AB  - Fatty bone marrow (BM) and defective hematopoiesis are a pathologic hallmark of
      aplastic anemia (AA). We have investigated adipogenic and osteogenic potential of
      BM mesenchymal stem cells (BM-MSC) in 10 AA patients (08 males and 02 females)
      with median age of 37 years (range: 06 to 79 years) and in the same number of age
      and sex matched controls. It was observed that BM-MSC of AA patients had a
      morphology, phenotype, and osteogenic differentiation potential similar to
      control subjects but adipocytes differentiated from AA BM-MSC had a higher
      density and larger size of lipid droplets and they expressed significantly higher
      levels of adiponectin and FABP4 genes and proteins as compared to control BM-MSC
      (P < 0.01 for both). Thus our data shows that AA BM-MSC have enhanced
      adipogenicity, which may have an important implication in the pathogenesis of the
      disease. 

PMID- 24876846
TI  - Bortezomib induced hepatitis B reactivation.
AB  - Background. It has recently been reported that hepatitis B (HBV) reactivation
      often occurs after the use of rituximab and stem cell transplantation in patients
      with lymphoma who are hepatitis B surface antigen (HBsAg) negative. However,
      clinical data on HBV reactivation in multiple myeloma (MM) is limited to only a
      few reported cases. Bortezomib and lenalidomide have remarkable activity in MM
      with manageable toxicity profiles, but reactivation of viral infections may
      emerge as a problem. We present a case of MM that developed HBV reactivation
      after bortezomib and lenalidomide therapy. Case Report. A 73-year-old female with
      a history of marginal cell lymphoma was monitored without requiring therapy. In
      2009, she developed MM, presenting as a plasmacytoma requiring vertebral
      decompression and focal radiation. While receiving radiation she developed renal
      failure and was started on bortezomib and liposomal doxorubicin. After a
      transient response to 5 cycles, treatment was switched to lenalidomide. Preceding
      therapy initiation, her serology indicated resolved infection. Serial monitoring
      for HBV displayed seroconversion one month after change in therapy. Conclusion.
      Bortezomib associated late HBV reactivation appears to be a unique event that
      requires further confirmation and brings to discussion whether hepatitis B core
      positive individuals would benefit from monitoring of HBV activation while on
      therapy. 

PMID- 24876849
TI  - The efficacy of mesenchymal stem cell transplantation in caustic esophagus
      injury: an experimental study.
AB  - Introduction. Ingestion of corrosive substances may lead to stricture formation
      in esophagus as a late complication. Full thickness injury seems to exterminate
      tissue stem cells of esophagus. Mesenchymal stem cells (MSCs) can differentiate
      into specific cell lineages and have the capacity of homing in sites of injury.
      Aim and Methods. We aimed to investigate the efficacy of MSC transplantation, on
      prevention of esophageal damage and stricture formation after caustic esophagus
      injury in rats. 54 rats were allocated into four groups; 4 rats were sacrificed
      for MSC production. Group 1, untreated controls (n: 10). Group 2, membrane
      labeled MSCs-treated rats (n: 20). Group 3, biodistribution of fluorodeoxyglucose
      labeled MSCs via positron emission tomography (PET) imaging (n: 10). Group 4,
      sham operated (n: 10). Standard caustic esophageal burns were created and MSCs
      were transplanted 24 hours after. All rats were sacrificed at the 21st days.
      Results. PET scan images revealed the homing behavior of MSCs to the injury site.
      The histopathology damage score was not significantly different from controls.
      However, we demonstrated Dil labeled epithelial and muscle cells which were
      originating from transplanted MSCs. Conclusion. MSC transplantation after caustic
      esophageal injury may be a helpful treatment modality; however, probably repeated
      infusions are needed. 

PMID- 24876850
TI  - Cryptosporidiosis in Iranian Farm Workers and Their Household Members: A
      Hypothesis about Possible Zoonotic Transmission.
AB  - Objectives. The prevalence of Cryptosporidium and the risk factors of zoonotic
      transmission in Najafabad, Isfahan, Iran dairy farms were examined. Methods. One
      fecal sample was collected from all calves less than 6 months old in eight dairy
      farms around Najafabad (Isfahan province, Central Iran) as well as individuals
      working in these farms and their household members. A two-step nested PCR
      protocol was used to amplify the 18S rRNA gene (830 bp). Results. Cryptosporidium
      was identified in the stool of 36 (prevalence 8.5%) of 96 farm workers and 326
      household members. Furthermore, 31 (14.2%) of 218 calf samples were positive.
      Cryptosporidium parvum was identified in 15 (72%) of the positive farm workers
      and 10 (65%) of the positive household members. Of the positive calves, 20
      (64.5%) were infected with C. parvum, indicating possible zoonotic transmission
      in these farms. Contact with calves (P < 0.0001) was the most significant risk
      factor of C. parvum infection. A considerable negative association was observed
      between C. parvum infection and cleaning of shoes/boots after daily work (P =
      0.004), hand washing (P = 0.013), and use of piped water (P < 0.006). In the
      multivariate analysis with logistic regression, only contact with calves was
      significant. Conclusion. Zoonotic transmission of C. parvum due to contact with
      calves is predominant among farm workers and their household members of this
      region and appropriate health measures must be applied to control the infection
      and decrease of zoonotic transmission of this parasite. 

PMID- 24876848
TI  - Clinical applications of mesenchymal stem cells in chronic diseases.
AB  - Extraordinary progress in understanding several key features of stem cells has
      been made in the last ten years, including definition of the niche, and
      identification of signals regulating mobilization and homing as well as partial
      understanding of the mechanisms controlling self-renewal, commitment, and
      differentiation. This progress produced invaluable tools for the development of
      rational cell therapy protocols that have yielded positive results in preclinical
      models of genetic and acquired diseases and, in several cases, have entered
      clinical experimentation with positive outcome. Adult mesenchymal stem cells
      (MSCs) are nonhematopoietic cells with multilineage potential to differentiate
      into various tissues of mesodermal origin. They can be isolated from bone marrow
      and other tissues and have the capacity to extensively proliferate in vitro.
      Moreover, MSCs have also been shown to produce anti-inflammatory molecules which
      can modulate humoral and cellular immune responses. Considering their
      regenerative potential and immunoregulatory effect, MSC therapy is a promising
      tool in the treatment of degenerative, inflammatory, and autoimmune diseases. It
      is obvious that much work remains to be done to increase our knowledge of the
      mechanisms regulating development, homeostasis, and tissue repair and thus to
      provide new tools to implement the efficacy of cell therapy trials. 

PMID- 24876851
TI  - Strategies to overcome antileishmanial drugs unresponsiveness.
AB  - In the absence of effective vector control measures and vaccines against
      leishmaniasis, effective chemotherapy remains the mainstay of treatment. As the
      armoury of antileishmanial drugs is limited, strategies should be made to target
      the emergence of drug resistance. The loss of efficacy of antimonials such as
      sodium stibogluconate in the Indian subcontinent which has been the mainstay of
      treatment for more than six decades has raised concern to save the other drugs.
      In the current review, we highlight various steps which could be implemented to
      halt the increasing unresponsiveness of drugs such as monitoring of therapy in
      the form of rational dosing and duration of treatment, understanding the
      mechanism of action of the drugs and drug resistance, identification of markers
      of resistance, distribution of drugs free of cost, evolution of effective
      combination therapy and immunotherapy, and proper management of HIV/VL
      coinfection and post-kala-azar dermal leishmaniasis (PKDL). Strong support from
      governmental agencies and local communities in the form of education and
      orientation programmes for feasibility of implementing these strategies and
      affordability within the context of their health systems is needed in controlling
      and preventing leishmaniasis. 

PMID- 24876852
TI  - Current Status of Coronary Intervention in Patients with ST-Segment Elevation
      Myocardial Infarction and Multivessel Coronary Artery Disease.
AB  - Primary percutaneous coronary intervention (PCI) is a standard interventional
      treatment modality for ST-segment elevation myocardial infarction (STEMI).
      Diagnostic coronary angiogram during PCI reveals multivessel coronary artery
      disease in about half of patients with STEMI, and it is difficult to make
      decision on the extent of intervention in these patients. Although
      revascularization for the infarct-related artery only is still effective for
      STEMI patients, several studies have reported the efficacy of multivessel
      revascularization during primary PCI, as well as in a staged PCI procedure.
      Clinicians should consider clinical aspects such as initial cardiogenic shock and
      myocardial viability when performing primary multivessel intervention, including
      the risks and benefits of multivessel revascularization in patients undergoing
      primary PCI. This review describes the current status of performing multivessel
      PCI in patients with STEMI and proposes an optimal revascularization strategy
      based on the previous literature. 

PMID- 24876853
TI  - Coronary circulation; macro or micro, that it the question.

PMID- 24876854
TI  - Association between Cardiac Troponin Level and Coronary Flow Reserve in Patients
      without Coronary Artery Disease: Insight from a Thermodilution Technique Using an
      Intracoronary Pressure Wire.
AB  - BACKGROUND AND OBJECTIVES: Cardiac troponins are associated with increased
      mortality, even among patients with no coronary artery disease. Elevated cardiac
      troponin levels are frequently observed in patients without significant coronary
      lesions, although the mechanism underlying this finding is unclear. The aim of
      our study was to evaluate the association between the levels of cardiac troponin
      and coronary flow reserve (CFR). SUBJECTS AND METHODS: We evaluated serum cardiac
      troponin-I in 19 patients (9 female; age 61.9+/-10.9 year-old). All patients had
      an ejection fraction >40% and angiographically normal coronary arteries.
      Simultaneous measurements of fractional flow reserve (FFR), the index of
      microcirculatory resistance (IMR), and CFR measurements using an intracoronary
      temperature- and pressure-sensing guidewire under basal conditions and during
      maximal hyperemia were performed in three vessels: the left anterior descending
      artery (LAD), left circumflex artery (LCX) and right coronary artery (RCA).
      RESULTS: All patients were followed for a median of 13 months. FFR, IMR, and CFR
      measurements were performed successfully in all subjects. Mean CFRs of LAD, LCX,
      and RCA were 1.98+/-1.20, 2.75+/-2.11, and 4.44+/-2.51, respectively. Mean IMRs
      of LAD, LCX and RCA were 33.28+/-18.78, 29.11+/-26.70, and 30.55+/-23.65,
      respectively. There was a poor correlation between CFR and troponin-I values in
      each vessel. In selecting the lowest value of CFR in each patient as the
      corresponding value, the lowest CFR was not associated with troponin-I levels (r=
      0.219, p=0.367). CONCLUSION: In patients without significant coronary lesions,
      the correlation between CFR and troponin-I level was not significant using a
      thermodilution technique. Further study of a larger population with longer-term
      follow-up may be needed to more fully understand microvascular dysfunction.

PMID- 24876855
TI  - Clinical Outcomes in Patients with Intermediate Coronary Stenoses: MINIATURE
      Investigators (Korea MultIceNter TrIal on Long-Term Clinical Outcome According to
      the Plaque Burden and Treatment Strategy in Lesions with MinimUm Lumen ARea lEss
      Than 4 mm(2) Using Intravascular Ultrasound).
AB  - BACKGROUND AND OBJECTIVES: We evaluated the two-year clinical outcomes in
      patients with angiographically intermediate lesions according to the plaque
      burden and treatment strategy. SUBJECTS AND METHODS: We prospectively enrolled
      patients with angiographically intermediate lesions (diameter stenosis 30-70%)
      with an intravascular ultrasound (IVUS) minimum lumen area (MLA) <4 mm(2) with 50
      70% plaque burden of 16 Korean percutaneous coronary intervention centers.
      Patients were divided into medical therapy group (n=85) and zotarolimus-eluting
      stent group (ZES; Resolute) group (n=74). We evaluated the incidences of two-year
      major adverse cardiovascular events (MACE). RESULTS: A two-year clinical follow
      up was completed in 143 patients and MACE occurred in 12 patients. There were no
      significant differences in the incidences of death (1.3% vs. 3.0%, p=0.471),
      target vessel-related non-fatal myocardial infarction (0.0% vs. 0.0%, p=1.000)
      and target vessel revascularizations (7.8% vs. 4.5%, p=0.425) between medical and
      ZES groups. Independent predictors of two-year MACE included acute myocardial
      infarction {odds ratio (OR)=2.87; 95% confidence interval (CI) 1.43-6.12,
      p=0.014}, diabetes mellitus (OR=2.46; 95% CI 1.24-5.56, p=0.028) and non-statin
      therapy (OR=2.32; 95% CI 1.18-5.24, p=0.034). CONCLUSION: Medical therapy shows
      comparable results with ZES, and myocardial infarction, diabetes mellitus and non
      statin therapy were associated with the occurrence of two-year MACE in patients
      with intermediate lesion with IVUS MLA <4 mm(2) with 50-70% of plaque burden.

PMID- 24876856
TI  - A pilot study of target weight guided treatment in acute heart failure using
      ultrafiltration or usual care: effect on sodium removal.
AB  - BACKGROUND AND OBJECTIVES: In the Ultrafiltration versus Intravenous Diuretics
      for Patients Hospitalized for Acute Decompensated Heart Failure trial,
      ultrafiltration (UF) removed volume more effectively than usual care (UC).
      Hypothetically, UF may be superior to UC due to increased sodium (Na) removal and
      less neurohormonal activation. We compared UF and UC in a randomized pilot trial
      of target weight guided therapy for acute decompensated heart failure (ADHF).
      SUBJECTS AND METHODS: Sixteen patients with ADHF were enrolled and target weights
      established prospectively, prior to randomization to UC or UF. UF patients did
      not receive diuretics and UC patients were all treated with a continuous
      furosemide drip. All urine and ultrafiltrate were collected and Na concentrations
      measured. RESULTS: Similar volumes were removed in UC and UF groups (110105 mL
      and 107415 mL, respectively) and the UF group also produced 45325 mL of urine. Na
      concentration was 138+/-6 meq/L in the ultrafiltrate, 85+/-73 meq/L in the UC
      group's urine, and 26+/-23 meq/L in the UF group's urine. Given the relevant
      associated volumes, total meq of the Na removed was similar (1168 in UC vs. 1216
      in UF). The UF group produced isotonic ultrafiltrate and a higher volume of
      dilute urine than anticipated. CONCLUSION: In a randomized pilot study of target
      weight guided therapy with UC or UF for ADHF, there were no differences in total
      volumes or Na removed, and lengths of hospital stays were similar. Isotonic fluid
      loss by UF was accompanied by the production of very dilute urine.

PMID- 24876857
TI  - Aortic aneurysm screening in a high-risk population: a non-contrast computed
      tomography study in korean males with hypertension.
AB  - BACKGROUND AND OBJECTIVES: Screening strategies for aortic aneurysm (AA)
      according to risk factors and ethnicity are controversial. This study explored
      the prevalence of AA and determined whether screening is necessary in a
      population of multiple risk factors. SUBJECTS AND METHODS: From June, 2012 to
      April, 2013, 542 consecutive elderly (>=65 years) male hypertensive patients
      without a history of AA were prospectively enrolled. After excluding 15 patients
      (2.8%) with aortic valve surgery, 30 patients (5.5%) with suboptimal computed
      tomography (CT) images, the remaining 496 patients (age 73+/-5 years) comprised
      the study population. Maximal diameters of the thoracic and abdominal aorta were
      measured using non-contrast CT. RESULTS: The prevalence of thoracic AA (TAA,
      diameter >=40 mm) and abdominal AA (AAA, diameter >=30 mm) was 36.5% (181/496)
      and 6.0% (30/496), respectively. In the multivariate logistic regression
      analysis, determinants for TAA were age {odds ratio (OR) 1.059, 95% confidence
      interval (CI) 1.018-1.101, p=0.005}, dyslipidemia (OR 0.621, 95% CI 0.418-0.923,
      p=0.018), body surface area (OR 11.92, 95% CI 2.787-50.97, p=0.001), diastolic
      blood pressure (OR 1.029, 95% CI 1.009-1.049, p=0.004) and AAA (OR 3.070, 95% CI
      1.398-6.754, p=0.005). In contrast, AAA was independently associated with
      dysplipidemia (OR 2.792, 95% CI 1.091-7.143, p=0.032), current/past smokerfs (OR
      4.074, 95% CI 1.160-14.31, p=0.028), and TAA (OR 3.367, 95% CI 1.550-7.313,
      p=0.002). CONCLUSION: The prevalence of AA was significant and TAA was more
      prevalent than AAA in elderly Korean males with hypertension. Future research
      should establish distinct screening strategies for TAA and AAA according to risk
      factors and ethnicity.

PMID- 24876858
TI  - Clinical Utility of Coronary CT Angiography with Stress Perfusion CT in
      Preoperative Cardiac Risk Evaluation.
AB  - BACKGROUND AND OBJECTIVES: Vascular surgery carries high operative risk. Recently
      developed cardiac computed tomography (CT) provides excellent imaging of coronary
      artery disease (CAD), as well as myocardial perfusions. We investigated the role
      of stress perfusion CT with coronary computed tomography angiography (CCTA) using
      128-slice dual source CT (DSCT) in preoperative cardiac risk evaluation. SUBJECTS
      AND METHODS: Patients scheduled for vascular surgery were admitted and underwent
      the adenosine stress perfusion CT with CCTA using DSCT. Patients who presented
      with unstable angina, recent myocardial infarction, decompensated heart failure,
      or renal failure were excluded. Stress perfusion CT was first acquired using
      sequential mode during adenosine infusion, after which, scanning for CT
      angiography was followed by helical mode. Perioperative events were followed up
      for 1 month. RESULTS: Ninety-one patients completed the study. Most patients
      (94.5%) had coronary atherosclerosis, with 36 (39.6%) patients had more than 50%
      coronary artery stenosis. Perfusion defects with significant stenosis were found
      in 12 cases (13.2%). Revascularization after DSCT was rarely performed. Four
      patients (4.4%) experienced cardiac events in the perioperative period: two
      experienced heart failure and two had non-fatal myocardial infarction.
      CONCLUSION: We cannot conclude that the stress perfusion CT, with CCTA using
      DSCT, plays a significant role in preoperative risk evaluation from this study.
      However, the coronary atherosclerosis and the significant CAD were commonly
      found. The perfusion defects with significant lesions were found in only small
      fraction of the patients, and did not contribute to perioperative myocardial
      infarction or heart failure.

PMID- 24876859
TI  - Angiopoietin-like 4 is involved in the poor angiogenic potential of high glucose
      insulted bone marrow stem cells.
AB  - BACKGROUND AND OBJECTIVES: Diabetes is reported to reduce the function or number
      of progenitor cells. We compared the gene expression patterns of bone marrow
      derived mesenchymal stem cells from diabetic (DM-BMCs) and healthy (non-DM-BMCs)
      rats and suggested Angiopoietin-like 4 (Angptl4) could be a responsible factor
      for impaired angiogenesis of DM-BMCs. SUBJECTS AND METHODS: BMCs were isolated
      from DM or non-DM rat, and in vitro angiogenesis activity was compared by tube
      formation assay on Matrigel and complementary deoxyribonucleic acid expression
      was analyzed by microarray with or without oxytocin treatment. Human BMCs (hBMCs)
      were treated with high glucose, and were performed polymerase chain reaction,
      Western blot, and enzyme-linked immunosorbent assay. Angptl4 plasmid DNA and
      micro ribonucleic acid-132 (miR-132) were transfected to immortalized hBMCs.
      RESULTS: In vitro angiogenesis assay showed the impaired tube formation in DM
      BMCs, and slightly recovery by oxytocin treatment. Angptl4, an adipokine, was
      upregulated in DM-BMCs compared to non-DM-BMCs. Oxytocin treatment reduced
      Angptl4 in DM-BMCs. In hBMCs, overexpression of Angptl4 attenuated the tube
      formation. In addition to Angptl4, miR-132 was increased by high glucose
      treatment. Collectively, high glucose resulted in impaired tube formation through
      miR-132 induction and Angptl4 upregulation in BMCs. CONCLUSION: Our results show
      that the angiogenic activity of BMCs is impaired by high glucose stress, which
      would be mediated by Angptl4 and miR-132.

PMID- 24876860
TI  - Retrograde distal superficial femoral artery approach in the supine position for
      chronic superficial femoral artery occlusion.
AB  - Subintimal angioplasty is an effective method for the treatment of long
      superficial femoral artery (SFA) occlusions. One of the major limiting factors
      for the success of this procedure is the failure to re-enter the true lumen. The
      recently introduced luminal re-entry devices provide a high technical success
      rate, but failures can occur. In such cases, a retrograde popliteal approach can
      serve as a potential backup option. However, the need to reposition the patient
      remains a drawback. Here, we report a case of an 81-year-old male with a long SFA
      occlusion treated using a retrograde distal SFA approach in the supine position
      after the initial failure of antegrade angioplasty. 

PMID- 24876861
TI  - Nonbacterial Thrombotic Endocarditis in a Patient with Bowel Infarction due to
      Mesenteric Vein Thrombosis.
AB  - Ante mortem cases of venous thrombosis in patients with nonbacterial thrombotic
      endocarditis (NBTE) have not yet been reported. We describe a rare case of NBTE
      in a patient with mesenteric vein thrombosis. A healthy 37-year-old man with
      abdominal pain and fever underwent emergency small bowel resection due to bowel
      ischemia resulting from mesenteric vein thrombosis. Transthoracic
      echocardiography revealed multiple mobile masses attached to the anterior leaflet
      of the mitral valves and their chordae tendineae. On suspicion of infective
      endocarditis, the cardiac masses were excised through open-heart surgery.
      However, pathologic reviews were compatible with NBTE. The patient was stable
      after the cardiac surgery and was treated with warfarin. Laboratory and imaging
      findings regarding his hypercoagulable condition were all negative. 

PMID- 24876862
TI  - Aorta-right atrial tunnel: an interesting type of a congenital coronary artery
      anomaly.
AB  - An 18-year-old girl with an aortico-right atrial tunnel originating from the left
      sinus of Valsalva, in which the left anterior descending and circumflex coronary
      arteries arose independently from the different parts of the tunnel, was
      reported. In the differential diagnosis of continuous murmur, this type of tunnel
      should be taken into consideration. Surgical approach should be offered. 

PMID- 24876863
TI  - An adult case of tetralogy of fallot accompanied by multiple anomalies including
      multidirectional coronary artery fistulas.
AB  - Multidirectional coronary artery fistulas (CAFs) are rare in patients with
      tetralogy of Fallot (TOF). We report an adult patient who underwent open-heart
      surgery for TOF 24 years before the discussed presentation. Coronary angiogram
      and cardiac computed tomography revealed multidirectional CAFs originating from
      the left main coronary artery and draining to the left atrium, pulmonary artery
      and subphrenic artery. The patient also showed additional congenital anomalies,
      such as persistent left superior vena cava and right-sided aortic arch. 

PMID- 24876864
TI  - Statins for patients with cardiogenic shock.

PMID- 24876867
TI  - Investigation of the Chemical Changes from Crude and Processed Paeoniae Radix
      Alba-Atractylodis Macrocephalae Rhizoma Herbal Pair Extracts by Using Q Exactive
      High-Performance Benchtop Quadrupole-Orbitrap LC-MS/MS.
AB  - The Paeoniae Radix Alba-Atractylodis Macrocephalae Rhizoma herbal pair is mainly
      used for regulating the functions of liver and spleen, benefiting qi, and
      nourishing blood. However, the bioactive compounds for the pharmacological
      activities of the crude and processed Paeoniae Radix Alba-Atractylodis
      Macrocephalae Rhizoma herbal pair extracts are still unclear to date. In the
      present study, Q Exactive high-performance benchtop quadrupole-Orbitrap LC-MS/MS
      was applied to identify the complicated components from crude and processed
      Paeoniae Radix Alba, crude and processed Atractylodis Macrocephalae Rhizoma, and
      their crude and processed herbal pair extracts. 123 and 101 compounds were
      identified in crude and processed Paeoniae Radix Alba samples, respectively.
      Meanwhile, 32 and 26 compounds were identified in crude and processed
      Atractylodis Macrocephalae Rhizoma samples, respectively. In the crude and
      processed Paeoniae Radix Alba-Atractylodis Macrocephalae Rhizoma herbal pair
      extracts, co-decoction could significantly change the chemical composition of
      Paeoniae Radix Alba and Atractylodis Macrocephalae Rhizoma in solution. The
      developed method may provide a scientific foundation for deeply elucidating the
      processing and compatibility mechanism of Paeoniae Radix Alba and Atractylodis
      Macrocephalae Rhizoma. 

PMID- 24876866
TI  - Ginseng and anticancer drug combination to improve cancer chemotherapy: a
      critical review.
AB  - Ginseng, a well-known herb, is often used in combination with anticancer drugs to
      enhance chemotherapy. Its wide usage as well as many documentations are often
      cited to support its clinical benefit of such combination therapy. However the
      literature based on objective evidence to make such recommendation is still
      lacking. The present review critically evaluated relevant studies reported in
      English and Chinese literature on such combination. Based on our review, we found
      good evidence from in vitro and in vivo animal studies showing enhanced antitumor
      effect when ginseng is used in combination with some anticancer drugs. However,
      there is insufficient clinical evidence of such benefit as very few clinical
      studies are available. Future research should focus on clinically relevant
      studies of such combination to validate the utility of ginseng in cancer. 

PMID- 24876868
TI  - Role of complementary and alternative medicine in controlling dyslipidemia.

PMID- 24876869
TI  - Potential retinoid x receptor agonists for treating Alzheimer's disease from
      traditional chinese medicine.
AB  - Alzheimer's disease is neurodegenerative disorder due to the accumulation of
      amyloid- beta in the brain and causes dementia with ageing. Some researches
      indicate that the RXR agonist, Targretin, has also been used for treatment of
      Alzheimer's disease in mouse models. We investigate the potent candidates as RXR
      agonists from the vast repertoire of TCM compounds in TCM Database@Taiwan. The
      potential TCM compounds, beta -lipoic acid and sulfanilic acid, had higher potent
      binding affinities than both 9-cis-retinoic acid and Targretin in docking
      simulation and have stable H-bonds with residues Arg316 and some equivalent
      hydrophobic contacts with residues Ala272, Gln275, Leu309, Phe313, Val342,
      Ile345, and Cys432 as Targretin. The carboxyl or sulfonyl hydroxide group can
      form a H-bond with key residue Arg316 in the docking pose, and the phenyl group
      next to the carboxyl or sulfonyl hydroxide group can form a pi interaction with
      residue Phe313. Moreover, beta -lipoic acid and sulfanilic acid have stable H
      bonds with residue Gln275, Ser313, and residue Ala327, respectively, which may
      strengthen and stabilize TCM candidates inside the binding domain of RXR protein.
      Hence, we propose beta -lipoic acid and sulfanilic acid as potential lead
      compounds for further study in drug development process with the RXR protein
      against Alzheimer's disease. 

PMID- 24876870
TI  - Lead Screening for HIV of C-C Chemokine Receptor Type 5 Receptor Inhibited by
      Traditional Chinese Medicine.
AB  - The acquired immunodeficiency syndrome (AIDS), caused by the human
      immunodeficiency virus (HIV), has become a serious world-wide problem because of
      this disease's rapid propagation and incurability. Recent research has pointed
      out that the C-C chemokine receptor type 5 (CCR5) is an important target for HIV
      infection. The traditional Chinese medicine (TCM) database
      (http://tcm.cmu.edu.tw/) has been screened for molecular compounds that, by
      simulating molecular docking and molecular dynamics, may protect CCR5 against
      HIV. Saussureamine C, 5-hydroxy-L-tryptophan, and abrine are selected based on
      the docking score being higher than Maraviroc and other TCM compounds. The
      molecular dynamics are helpful in the analysis and detection of protein-ligand
      interactions. According to the docking poses, hydrophobic interactions, and
      hydrogen bond variations, this research surmises TRP86, TYR108, GLN194, TYR251,
      and GLU283 are the main regions of important amino acids in CCR5. In addition to
      the detection of TCM compound efficacy, we suggest saussureamine C is better than
      the others for maintaining protein composition during protein-ligand interaction,
      based on the structural variation. 

PMID- 24876871
TI  - Supplementation with the extract of schisandrae fructus pulp, seed, or their
      combination influences the metabolism of lipids and glucose in mice fed with
      normal and hypercholesterolemic diet.
AB  - SCHISANDRAE FRUCTUS (SF), WHICH POSSESSES FIVE TASTES: sweet (fruit skin), sour
      (pulp), bitter/pungent (seed core), and saltiness (all parts), can produce a wide
      spectrum of biological activities in the body. Here, we investigated the effects
      of the ethanolic extract of SF pulp, seed, or their combination (namely, EtSF-P,
      EtSF-S, or EtSF-P/S, resp.; collectively called EtSF) on the metabolism of lipids
      and glucose in normal diet- (ND-) and hypercholesterolemic diet- (HCLD-) fed
      mice. Supplementation with EtSF significantly reduced hepatic triglyceride and
      cholesterol levels by 18-47% in both ND- and HCLD-fed mice. EtSF supplementation
      reduced serum triglyceride levels (approximately 29%), whereas EtSF-P and EtSF
      S/P elevated serum cholesterol (up to 26 and 44%, resp.) in HCLD-fed mice.
      Treatment with EtSF decreased hepatic glucose levels (by 9-44%) in both ND- and
      HCLD-fed mice. Supplementation with EtSF-S or EtSF-S/P (at 1 and 3%) increased
      biliary or fecal TC contents in HCLD-fed mice. However, supplementation with EtSF
      S/P at 9% reduced biliary TC levels in HCLD-fed mice. EtSF-P or EtSF-S/P
      supplementation reduced serum alanine aminotransferase activity in HCLD-fed mice.
      The findings suggested that supplementation with EtSF lowered lipid and glucose
      accumulation in the liver and increased fecal cholesterol contents in mice.
      Dietary supplementation with EtSF-P or EtSF-S/P attenuated liver damage in HCLD
      fed mice.

PMID- 24876872
TI  - Evaluation of Preclinical Assays to Investigate an Anthroposophic Pharmaceutical
      Process Applied to Mistletoe (Viscum album L.) Extracts.
AB  - Extracts from European mistletoe (Viscum album L.) developed in anthroposophic
      medicine are based on specific pharmaceutical procedures to enhance remedy
      efficacy. One such anthroposophic pharmaceutical process was evaluated regarding
      effects on cancer cell toxicity in vitro and on colchicine tumor formation in
      Lepidium sativum. Anthroposophically processed Viscum album extract (APVAE) was
      produced by mixing winter and summer mistletoe extracts in the edge of a high
      speed rotating disk and was compared with manually mixed Viscum album extract
      (VAE). The antiproliferative effect of VAE/APVAE was determined in five cell
      lines (NCI-H460, DU-145, HCC1143, MV3, and PA-TU-8902) by WST-1 assay in vitro;
      no difference was found between VAE and APVAE in any cell line tested (P > 0.14).
      Incidence of colchicine tumor formation was assessed by measurement of the
      root/shoot-ratio of seedlings of Lepidium sativum treated with colchicine as well
      as VAE, APVAE, or water. Colchicine tumor formation decreased after application
      of VAE (-5.4% compared to water, P < 0.001) and was even stronger by APVAE (-8.8%
      compared to water, P < 0.001). The high-speed mistletoe extract mixing process
      investigated thus did not influence toxicity against cancer cells but seemed to
      sustain morphostasis and to enhance resistance against external noxious
      influences leading to phenomenological malformations. 

PMID- 24876873
TI  - Ameliorating Adriamycin-Induced Chronic Kidney Disease in Rats by Orally
      Administrated Cardiotoxin from Naja naja atra Venom.
AB  - Previous studies reported the oral administration of Naja naja atra venom (NNAV)
      reduced adriamycin-induced chronic kidney damage. This study investigated the
      effects of intragastric administrated cardiotoxin from Naja naja atra venom on
      chronic kidney disease in rats. Wistar rats were injected with adriamycin (ADR; 6
      mg/kg body weight) via the tail vein to induce chronic kidney disease. The
      cardiotoxin was administrated daily by intragastric injection at doses of 45, 90,
      and 180  MU g/kg body weight until the end of the protocol. The rats were placed
      in metabolic cages for 24 hours to collect urine, for determination of
      proteinuria, once a week. After 6 weeks, the rats were sacrificed to determine
      serum profiles relevant to chronic kidney disease, including albumin, total
      cholesterol, phosphorus, blood urea nitrogen, and serum creatinine. Kidney
      histology was examined with hematoxylin and eosin, periodic acid-Schiff, and
      Masson's trichrome staining. The levels of kidney podocin were analyzed by
      Western blot analysis and immunofluorescence. We found that cardiotoxin reduced
      proteinuria and can improve biological parameters in the adriamycin-induced
      kidney disease model. Cardiotoxin also reduced adriamycin-induced kidney
      pathology, suggesting that cardiotoxin is an active component of NNAV for
      ameliorating adriamycin-induced kidney damage and may have a potential
      therapeutic value on chronic kidney disease. 

PMID- 24876874
TI  - In vivo lipid regulation mechanism of polygoni multiflori radix in high-fat diet
      fed rats.
AB  - Mechanisms of the water extracts of Polygoni Multiflori Radix (PMR) and its
      processed products (PMRP) on liver lipid metabolism were observed in this paper.
      Aqueous extract of PMR and PMRP was given to nonalcoholic fatty liver model rats,
      respectively. PMR was better in reducing the contents of very low density
      lipoprotein (VLDL) than PMRP and the positive control groups. In the aspect of
      regulating TG, medium dose PMR reduced the activity of diacylglycerol
      acyltransferase (DGAT) to 1536 +/- 47.69 pg/mL (P < 0.001) and promoted the
      expression of hepatic lipase (HL) to 23.59 +/- 0.2758 U/mL (P < 0.05). HL
      promotion ability of medium dose PMR was similar with the simvastatin positive
      control. Both medium and high dose of PMR showed significant alterations in TC,
      which were related to the downregulation effects on hydroxyl methyl-glutaryl
      coenzyme A reductase (HMGCR) and upregulation effects on cholesterol 7-alpha
      hydroxylase or cytochrome P450 7A (CYP7A). Quantitative relationships research
      indicated that the prominent effect on inhibiting the content of HMGCR (r =
      0.756, P < 0.05) was strongly positive correlated with to the TC regulation
      effects. Effects of PMR on enhancing decomposition rate or reducing de novo
      synthesis rate of TG and TC were better than PMRP. 

PMID- 24876875
TI  - Effect of Eclipta prostrata on 11Beta-Hydroxysteroid Dehydrogenase in Rat Liver
      and Kidney.
AB  - Eclipta prostrata (EP) is often prescribed in combination with glucocorticoid to
      treat glomerular nephritis, nephrotic syndrome, and IgA nephropathy in clinical
      practice of Traditional Chinese Medicine. Previous studies from our laboratory
      revealed that coadministration of EP significantly increased the plasma
      concentration of prednisolone while decreased the level of cotreated prednisone
      in rats. However, the underlying mechanism remains unclear. 11 beta 
      Hydroxysteroid dehydrogenase (11 beta -HSD) belongs to the family of
      oxidoreductases that catalyze the interconversion of prednisone to active
      prednisolone. Therefore, the current study aimed to investigate the effects of EP
      on the activity and expression of 11 beta -HSD in rat liver and kidney. The
      results showed that oral administration of EP significantly increased the
      activity of 11 beta -HSD I in the liver and 11 beta -HSD II in the kidney by
      employing the microsomal incubation system. Moreover, gene and protein
      expressions of 11 beta -HSD I and 11 beta -HSD II were also increased in rat
      liver and kidney, respectively. These results suggest that the effects of EP on
      11 beta -HSD may attribute to the mechanism that administration of EP improves
      the efficacy and reduces adverse drug reactions of glucocorticoid in patients
      undergoing combinational therapy. 

PMID- 24876876
TI  - Somatosensory Nerve Fibers Mediated Generation of De-qi in Manual Acupuncture and
      Local Moxibustion-Like Stimuli-Modulated Gastric Motility in Rats.
AB  - The aim of this study was to reveal the somatosensory nerve fibers mediated
      generation of De-qi in manual acupuncture stimuli (MAS) and local moxibustion
      like stimuli (LMS). The effects of strong and slight MAS, as well as 41 degrees
      C, 43 degrees C, and 45 degrees C LMS at ST36 and CV12 on gastric motility were
      observed in rats. Gastric motility was continuously measured by an intrapyloric
      balloon, and the average amplitude, integral, and frequency of gastric motility
      during LMS were compared with those of background activity. Gastric motility was
      facilitated by MAS and LMS at ST36 and inhibited at CV12. The modulatory effects
      induced by strong MA with potent De-qi (needle grasp feeling) were markedly
      higher than those by slight MA with mild De-qi sensation (P < 0.05). The
      nociceptive 43 degrees C and 45 degrees C LMS, rather than nonnociceptive 41
      degrees C LMS, produced significant regulatory effects on gastric motility. Based
      on the afferent fibers activated in the present study, these results support the
      hypothesis that A delta - and C-afferent fibers were more likely to be involved
      in the generation of De-qi sensation. 

PMID- 24876877
TI  - Genus caulophyllum: an overview of chemistry and bioactivity.
AB  - Recently, some promising advances have been achieved in understanding the
      chemistry, pharmacology, and action mechanisms of constituents from genus
      Caulophyllum. Despite this, there is to date no systematic review of those of
      genus Caulophyllum. This review covers naturally occurring alkaloids and saponins
      and those resulting from synthetic novel taspine derivatives. The paper further
      discussed several aspects of this genus, including pharmacological properties,
      mechanisms of action, pharmacokinetics, and cell membrane chromatography for
      activity screening. The aim of this paper is to provide a point of reference for
      pharmaceutical researchers to develop new drugs from constituents of Caulophyllum
      plants. 

PMID- 24876878
TI  - The protective effect of aged garlic extract on nonsteroidal anti-inflammatory
      drug-induced gastric inflammations in male albino rats.
AB  - Natural products have long gained wide acceptance among the public and scientific
      community in the gastrointestinal ulcerative field. The present study explore the
      potential effects of aged garlic extract (AGE) on indomethacin-(IN-) induced
      gastric inflammation in male rats. Animals were divided into six groups (n = 8)
      control group, IN-induced gastric inflammation group via oral single dose (30
      mg/kg to fasted rats) two AGE orally administered groups (100 and 200 mg/kg for
      30 consecutive days) two AGE orally administered groups to rats pretreated with
      IN at the same aforementioned doses. The results declared the more potent effect
      of the higher AGE dose (200 mg/kg) as compared to that of the 100 mg/kg dose in
      the gastroprotective effects reflected by significant gastric mucosal healing of
      damage and reduction in the total microbial induced due to indomethacin
      administration. In addition to the significant effect to normalize the
      significant increase in malondialdehyde (MDA), myeloperoxidase (MPO), tumor
      necrosis factor- alpha (TNF- alpha ) values, and the significant decrease in the
      total glutathione (tGSH), superoxide dismutase (SOD), and catalase (CAT) values
      induced by indomethacin. The results support AGE antioxidant, anti-inflammatory,
      and antimicrobial potency reflected by the healing of the gastric tissue damage
      induced by indomethacin. 

PMID- 24876879
TI  - Do changes in electrical skin resistance of acupuncture points reflect menstrual
      pain? A comparative study in healthy volunteers and primary dysmenorrhea
      patients.
AB  - Electrical skin resistance (ESR) measurements were performed with a four
      electrode impedance detector at 10 points bilaterally on the first day of and the
      third day after menstruation in 48 healthy volunteers and 46 primary dysmenorrhea
      (PD) patients, to assess whether ESR changes of acupuncture points can reflect
      menstrual pain or not. The results showed statistical reductions in ESR imbalance
      ratio between left and right side that were detected at SP8 (Diji) and GB39
      (Xuanzhong) (P < 0.05), and a statistical increase was detected at SP6
      (Sanyinjiao) (P = 0.05) on the first day of menstruation compared with those
      values on the third day after menstruation in dysmenorrhea group. No significant
      differences were detected at other points within and between two groups (P >
      0.05). This study showed that the imbalance of ESR at uterine-relevant points in
      PD patients is not significantly different from those of healthy women on both
      the 1st day of and the 3rd day after menstruation. The ESR imbalance ratio of
      certain points can either be lower or higher during menstruation in PD patients.
      The ESR property of acupuncture points needs to be investigated in further
      clinical trials with appropriate points, diseases, larger sample sizes, and
      optimal device. 

PMID- 24876880
TI  - Investigation of anti-infection mechanism of lactoferricin and splunc-1.
AB  - The innate immune system is the first line in the defense system and prevents the
      body from further bacteria, virus, or fungal infections. Most of the innate
      immune system is relevant to mucosa immunity. Lactotransferrin is secreted from
      the human mammal breast duct epithelial tissue and strengthens infant immunity to
      defense with regard to outward pathogens. Splunc-1 is also an innate material
      secreted from the soft palate, lung, nasal cavity epithelium, and mucosa. It
      helps with mucosa defense against bacterial, virus, and even fungus. LPS is the
      main etiology of Gram-negative bacilla infection source. And studies of
      lactoferricin and slpunc-1 both can combine with LPS and subsequently cause
      insults to the mucosa. Although, we know that both of them partake in an
      important role in innate immunity, we do not know the effects when they work
      together. In this study, we just overview silicon stimulation to examine the
      combination of Lactoferricin and Splunc-1 and the effect with regard to LPS. 

PMID- 24876881
TI  - In Silico Investigation of Potential PARP-1 Inhibitors from Traditional Chinese
      Medicine.
AB  - Poly(ADP-ribose) polymerases (PARPs) are nuclear enzymes which catalyze the poly
      ADP-ribosylation involved in gene transcription, DNA damage repair, and cell
      death signaling. As PARP-1 protein contains a DNA-binding domain, which can bind
      to DNA strand breaks and repair the damaged DNA over a low basal level, the
      inhibitors of poly(ADP-ribose) polymerase 1 (PARP-1) have been indicated as the
      agents treated for cancer. This study employed the compounds from TCM
      Database@Taiwan to identify the potential PARP-1 inhibitors from the vast
      repertoire of TCM compounds. The binding affinities of the potential TCM
      compounds were also predicted utilized several distinct scoring functions.
      Molecular dynamics simulations were performed to optimize the result of docking
      simulation and analyze the stability of interactions between protein and ligand.
      The top TCM candidates, isopraeroside IV, picrasidine M, and aurantiamide
      acetate, had higher potent binding affinities than control, A927929. They have
      stable H-bonds with residues Gly202 and, Ser243 as A927929 and stable H-bonds
      with residues Asp105, Tyr228, and His248 in the other side of the binding domain,
      which may strengthen and stabilize ligand inside the binding domain of PARP-1
      protein. Hence, we propose isopraeroside IV and aurantiamide acetate as potential
      lead compounds for further study in drug development process with the PARP-1
      protein. 

PMID- 24876882
TI  - Si-jun-zi decoction treatment promotes the restoration of intestinal function
      after obstruction by regulating intestinal homeostasis.
AB  - Intestinal obstruction is a common disease requiring abdominal surgery with
      significant morbidity and mortality. Currently, an effective medical treatment
      for obstruction, other than surgical resection or decompression, does not exist.
      Si-Jun-Zi Decoction is a famous Chinese medicine used to replenish qi and
      invigorate the functions of the spleen. Modern pharmacological studies show that
      this prescription can improve gastrointestinal function and strengthen immune
      function. In this study, we investigated the effects of a famous Chinese herbal
      formula, Si-Jun-Zi Decoction, on the restoration of intestinal function after the
      relief of obstruction in a rabbit model. We found that Si-Jun-Zi Decoction could
      reduce intestinal mucosal injury while promoting the recovery of the small
      intestine. Further, Si-Jun-Zi Decoction could regulate the intestinal immune
      system. Our results suggest that Si-Jun-Zi Decoction promotes the restoration of
      intestinal function after obstruction by regulating intestinal homeostasis. Our
      observations indicate that Si-Jun-Zi Decoction is potentially a therapeutic drug
      for intestinal obstruction. 

PMID- 24876883
TI  - Electroacupuncture Ameliorates Acute Lung Injury through Promoting
      Gastrointestinal Motility in Rats with Acute Pancreatitis.
AB  - Objective. Gastrointestinal disfunction and acute lung injury (ALI) were common
      in acute pancreatitis (AP). The effect of electro-acupuncture (EA) on
      gastrointestinal motility and ALI in rats with AP was investigated to verify the
      theory of "lung and large intestine are interior exteriorly related" in
      traditional Chinese medicine. Methods. Male Sprague-Dawley rats were randomly
      divided into the normal group, model group, and EA group. AP model was
      established by three injections of 20% L-arginine at 1 h intervals. EA were
      applied to bilateral ST-25 and ST-36 for 30 minutes twice a day after modeling
      for 3 days. Arterial blood, pancreas, lung, and intestinal tissues were collected
      for detecting the inflammatory factors and histopathology. Intestinal propulsion
      rate (IPR) was also measured at 72 h. Results. EA treatment improved IPR and
      increased CCK-8 level compared with model group (P < 0.05). It lowered the serum
      levels of TNF- alpha and IL-6 and increased the level of IL-4 with no effect on
      IL-10. EA treatment reduced serum vasoactive intestinal peptide (VIP) and
      myeloperoxidase (MPO) level in the lung and the pathologic scores of pancreas,
      lung and intestine were decreased (P < 0.05). Conclusion. EA treatment could
      promote gastrointestinal motility through inhibiting VIP, and promoting CCK
      expression and regulate pro- and anti-inflammatory mediators to ameliorate ALI in
      AP. 

PMID- 24876884
TI  - Ethnobotanical Study of Herbaceous Flora along an Altitudinal Gradient in
      Bharmour Forest Division, District Chamba of Himachal Pradesh, India.
AB  - The present ethnobotanical study was carried out in Holi (Deol, Kut, Dal, and
      Lahaud Dhar) forest range and in Bharmor (Seri, Bharmour, Malkauta, Bharmani,
      Harsar, Dhancho, Sundrasi, Gorikund, and Manimahesh) forest range to obtain
      information on the plants used by the local inhabitants for several purposes. A
      total of 54 plants were recorded in this study. The plants are employed to treat
      simple diseases (cough, cold, fever, and burns) and some serious diseases
      (typhoid, jaundice, and kidney disease). Some of the plants are also used as
      incense for religious ceremonies and several other daily needs. But due to
      absence of scientific monitoring of plants, their cultivation, harvesting, and
      management techniques as well as sustainable use and lack of awareness of social
      factors, the availability of valuable plant resources is decreasing at an
      alarming rate. In addition, the indigenous knowledge regarding the use of lesser
      known plants of this region is also rapidly declining. Therefore, the
      documentation of plant resources is a necessary step towards the goal of raising
      awareness in local communities about the importance of these plants and their
      further conservation. 

PMID- 24876885
TI  - Neurological effects of honey: current and future prospects.
AB  - Honey is the only insect-derived natural product with therapeutic, traditional,
      spiritual, nutritional, cosmetic, and industrial value. In addition to having
      excellent nutritional value, honey is a good source of physiologically active
      natural compounds, such as polyphenols. Unfortunately, there are very few current
      research projects investigating the nootropic and neuropharmacological effects of
      honey, and these are still in their early stages. Raw honey possesses nootropic
      effects, such as memory-enhancing effects, as well as neuropharmacological
      activities, such as anxiolytic, antinociceptive, anticonvulsant, and
      antidepressant activities. Research suggests that the polyphenol constituents of
      honey can quench biological reactive oxygen species and counter oxidative stress
      while restoring the cellular antioxidant defense system. Honey polyphenols are
      also directly involved in apoptotic activities while attenuating microglia
      induced neuroinflammation. Honey polyphenols are useful in improving memory
      deficits and can act at the molecular level. Therefore, the ultimate biochemical
      impact of honey on specific neurodegenerative diseases, apoptosis, necrosis,
      neuroinflammation, synaptic plasticity, and behavior-modulating neural circuitry
      should be evaluated with appropriate mechanistic approaches using biochemical and
      molecular tools. 

PMID- 24876886
TI  - Scale effects and morphological diversification in hindlimb segment mass
      proportions in neognath birds.
AB  - INTRODUCTION: In spite of considerable work on the linear proportions of limbs in
      amniotes, it remains unknown whether differences in scale effects between
      proximal and distal limb segments has the potential to influence locomotor costs
      in amniote lineages and how changes in the mass proportions of limbs have
      factored into amniote diversification. To broaden our understanding of how the
      mass proportions of limbs vary within amniote lineages, I collected data on
      hindlimb segment masses - thigh, shank, pes, tarsometatarsal segment, and digits 
      from 38 species of neognath birds, one of the most speciose amniote clades. I
      scaled each of these traits against measures of body size (body mass) and
      hindlimb size (hindlimb length) to test for departures from isometry.
      Additionally, I applied two parameters of trait evolution (Pagel's lambda and
      delta) to understand patterns of diversification in hindlimb segment mass in
      neognaths. RESULTS: All segment masses are positively allometric with body mass.
      Segment masses are isometric with hindlimb length. When examining scale effects
      in the neognath subclade Land Birds, segment masses were again positively
      allometric with body mass; however, shank, pedal, and tarsometatarsal segment
      masses were also positively allometric with hindlimb length. Methods of branch
      length scaling to detect phylogenetic signal (i.e., Pagel's lambda) and
      increasing or decreasing rates of trait change over time (i.e., Pagel's delta)
      suffer from wide confidence intervals, likely due to small sample size and deep
      divergence times. CONCLUSIONS: The scaling of segment masses appears to be more
      strongly related to the scaling of limb bone mass as opposed to length, and the
      scaling of hindlimb mass distribution is more a function of scale effects in limb
      posture than proximo-distal differences in the scaling of limb segment mass.
      Though negative allometry of segment masses appears to be precluded by the need
      for mechanically sound limbs, the positive allometry of segment masses relative
      to body mass may underlie scale effects in stride frequency and length between
      smaller and larger neognaths. While variation in linear proportions of limbs
      appear to be governed by developmental mechanisms, variation in mass proportions
      does not appear to be constrained so.

PMID- 24876887
TI  - Effect of acid suppression therapy on gastroesophageal reflux and cough in
      idiopathic pulmonary fibrosis: an intervention study.
AB  - BACKGROUND: Chronic cough affects more than 70 percent of patients with
      Idiopathic Pulmonary Fibrosis and causes significant morbidity. Gastroesophageal
      reflux is the cause of some cases of chronic cough; and also has a postulated
      role in the aetiology of Idiopathic Pulmonary Fibrosis. A high prevalence of
      acid; and more recently non-acid, reflux has been observed in Idiopathic
      Pulmonary Fibrosis cohorts. Therefore, gastroesophageal reflux may be implicated
      in the pathogenesis of cough in Idiopathic Pulmonary Fibrosis. METHODS: Eighteen
      subjects with Idiopathic Pulmonary Fibrosis underwent 24-hour oesophageal
      impedance and cough count monitoring after the careful exclusion of causes of
      chronic cough other than gastroesophageal reflux. All 18 were then treated with
      high dose acid suppression therapies. Fourteen subjects underwent repeat 24-hour
      oesophageal impedance and cough count monitoring after eight weeks. RESULTS:
      Total reflux and acid reflux frequencies were within the normal range in the
      majority of this cohort. The frequencies of non-acid and proximal reflux events
      were above the normal range. Following high dose acid suppression therapy there
      was a significant decrease in the number of acid reflux events (p = 0.02), but an
      increase in the number of non-acid reflux events (p = 0.01). There was no change
      in cough frequency (p = 0.70). CONCLUSIONS: This study confirms that non-acid
      reflux is prevalent; and that proximal oesophageal reflux occurs in the majority,
      of subjects with Idiopathic Pulmonary Fibrosis. It is the first study to
      investigate the effect of acid suppression therapy on gastroesophageal reflux and
      cough in patients with Idiopathic Pulmonary Fibrosis. The observation that cough
      frequency does not improve despite verifiable reductions in oesophageal acid
      exposure challenges the role of acid reflux in Idiopathic Pulmonary Fibrosis
      associated cough. The finding that non-acid reflux is increased following the use
      of acid suppression therapies cautions against the widespread use of acid
      suppression in patients with Idiopathic Pulmonary Fibrosis given the potential
      role for non-acid reflux in the pathogenesis of cough and Idiopathic Pulmonary
      Fibrosis itself. STUDY REGISTRATION: The study was registered with the Cardiff
      and Vale University Local Health Board Research and Development Committee
      (09/CMC/4619) and the South East Wales Ethics Committee (09/WSE04/57).

PMID- 24876888
TI  - Changes of anxiety in Chinese military personnels over time: a cross-temporal
      meta-analysis.
AB  - BACKGROUND: Previous cross-temporal meta-analyses have demonstrated that anxiety
      would get severer over time. The changes of anxiety in Chinese military
      personnels over time remain unclear. AIM: To explore the changes of anxiety in
      Chinese military personnels over nearly past two decades. METHODS: Studies using
      the Chinese version of Spielberger's State-Trait Anxiety Inventory (STAI) in
      Chinese serviceman on active duty were primarily collected. Mean, standard
      deviation and sample size of each study were extracted for meta-analysis. With
      sample size of each study as weighted least-squares weight, we regressed the mean
      scores on the data collection year to evaluate changes in anxiety from 1991 to
      2011. Correlations between the anxiety scores and some social indicators were
      also examined. RESULTS: The final sample consisted of 45 separate studies with a
      total of 18,106 participants for state anxiety and 21,047 participants for trait
      anxiety. Both state anxiety and trait anxiety significantly increased over the
      past two decades. The effect sizes for state anxiety and trait anxiety were 0.88
      and 0.63, respectively. Anxiety scores were significantly correlated with some
      social indicators (e.g., crime rate, unemployment rate) of the corresponding
      years or 5 years prior to the anxiety data collection. CONCLUSIONS: Some measures
      must be taken to tackle the problem of the rising anxiety scores. Given that
      Chinese military personnels are continuing to experience high levels of anxiety,
      it is crucial to consider the implications for mental health care and treatment.
      More cross-temporal meta-analyses are needed to examine the changes of mental
      health in Chinese military personnels over time.

PMID- 24876889
TI  - Consolidated bioprocessing of transgenic switchgrass by an engineered and evolved
      Clostridium thermocellum strain.
AB  - BACKGROUND: Switchgrass is an abundant and dedicated bioenergy feedstock, however
      its inherent recalcitrance is one of the economic hurdles for producing biofuels.
      The downregulation of the caffeic acid O-methyl transferase (COMT) gene in the
      lignin pathway of switchgrass reduced lignin content and S/G ratio, and the
      transgenic lines showed improved fermentation yield with Saccharomyces cerevisiae
      and wild-type Clostridium thermocellum (ATCC 27405) in comparison to the wild
      type switchgrass. RESULTS: Here we examine the conversion and yield of the COMT
      transgenic and wild-type switchgrass lines with an engineered and evolved C.
      thermocellum (M1570) strain. The fermentation of the transgenic switchgrass by
      M1570 had superior conversion relative to the wild-type control switchgrass line
      with an increase in conversion of approximately 20% and ethanol being the primary
      product accounting for 90% of the total metabolites measured by HPLC analysis.
      CONCLUSIONS: The engineered and evolved C. thermocellum M1570 was found to
      respond to the apparent reduced recalcitrance of the COMT switchgrass with no
      substrate inhibition, producing more ethanol on the transgenic feedstock than the
      wild-type substrate. Since ethanol was the main fermentation metabolite produced
      by an engineered and evolved C. thermocellum strain, its ethanol yield on a
      transgenic switchgrass substrate (gram/gram (g/g) glucan liberated) is the
      highest produced thus far. This result indicates that the advantages of a
      modified feedstock can be combined with a modified consolidated bioprocessing
      microorganism as anticipated.

PMID- 24876891
TI  - Osteoblastoma arising from the orbital roof.

PMID- 24876890
TI  - Expanding the fragrance chemical space for virtual screening.
AB  - The properties of fragrance molecules in the public databases SuperScent and
      Flavornet were analyzed to define a "fragrance-like" (FL) property range (Heavy
      Atom Count <= 21, only C, H, O, S, (O + S) <= 3, Hydrogen Bond Donor <= 1) and
      the corresponding chemical space including FL molecules from PubChem (NIH
      repository of molecules), ChEMBL (bioactive molecules), ZINC (drug-like
      molecules), and GDB-13 (all possible organic molecules up to 13 atoms of C, N, O,
      S, Cl). The FL subsets of these databases were classified by MQN (Molecular
      Quantum Numbers, a set of 42 integer value descriptors of molecular structure)
      and formatted for fast MQN-similarity searching and interactive exploration of
      color-coded principal component maps in form of the FL-mapplet and FL-browser
      applications freely available at http://www.gdb.unibe.ch. MQN-similarity is shown
      to efficiently recover 15 different fragrance molecule families from the
      different FL subsets, demonstrating the relevance of the MQN-based tool to
      explore the fragrance chemical space. 

PMID- 24876892
TI  - Human brucellosis: seroprevalence and associated exposure factors among abattoir
      workers in Abuja, Nigeria - 2011.
AB  - INTRODUCTION: Brucellosis, a neglected debilitating zoonosis, is a recognized
      occupational hazard with a high prevalence in developing countries. Transmission
      to humans can occur through contact with infected animals or animal products.
      Brucellosis presents with fever. In Nigeria, there is a possibility of missed
      diagnoses by physicians leading to a long debilitating illness. We conducted a
      study to determine the seroprevalence and factors associated with Human
      Brucellosis (HB) among abattoir-workers in Abuja, Nigeria. METHODS: We conducted
      a cross-sectional study and selected abattoir-workers using stratified random
      sampling. Structured questionnaires were used to collect data on demographics and
      exposure-factors. We tested the workers' serum-samples using Rose-Bengal (RBPT)
      and ELISA tests. A worker with HB was one whose serum tested positive to RBPT or
      ELISA. We tested differences in proportions between workers with HB and those
      without HB using odds-ratio and X(2) tests. RESULTS: Of 224 workers, 172 (76.8%)
      were male and mean age was 30 + 9.0 years. Of 224 sera collected, 54 were
      positive giving a seroprevalence of 24.1%. Of these, 32 (59.3%) were butchers,
      and 11 (20.4%) were meat-sellers. Slaughtering animals while having open-wounds
      (Odds-ratio (OR) = 2.15, 95% Confidence Interval (CI) = 1.15-4.04); occupational
      exposure of >5years (OR = 2.30, CI = 1.11-4.78) and eating raw meat (OR = 2.75,
      CI = 1.21-6.26) were significantly associated with HB. Multivariate analyses
      showed that occupational-exposure of >5years (Adjusted OR (AOR) =2.45, CI = 1.15 
      5.30) and eating raw-meat (AOR = 2.64, CI = 1.14 - 6.14) remained significantly
      associated with HB. CONCLUSION: Seroprevalence of HB among abattoir-workers in
      Abuja was high. Factors associated with HB were occupational-exposure of >5years
      and eating raw-meat. Abattoir-workers should be discouraged from eating raw-meat
      and educated on adherence to safe animal-product handling practices.

PMID- 24876894
TI  - [Xeroderma pigmentosum and dermoscopy].

PMID- 24876893
TI  - Traumatic spinal cord injury in Saudi Arabia: a review of the literature.
AB  - Traumatic Spinal Cord Injury (TSCI) is a condition where the neural elements
      suffer acute trauma, resulting in short-term or permanent sensory and motor
      problems. An understanding the underlying structural and functional biological
      repairs of the TSCI mechanisms has intensely increased over the last two decades.
      However, compared with the other fields in medicine, the present degree of
      treatment and care for TSCI are quite unsatisfactory. The Kingdom of Saudi Arabia
      (KSA), the largest country in the Middle East, occupies nearly four-fifths of the
      Arabian Peninsula with a population of over 28 million. It also has the
      distinction of having one of the highest rates of spinal cord injuries in the
      world. However, research on TSCI has been very limited. Therefore, studies on the
      long-term incidence of TSCI in Saudi Arabia are vital and most essential to
      identify the high-risk groups, create awareness, establish trends, predict the
      needs, and thus contribute to effective health care planning of this condition.
      In this review, we discuss various aspects of TSCI in Saudi Arabia from the
      available literature. 

PMID- 24876895
TI  - Ruptured heterotopic pregnancy in a natural conception cycle: a case report at
      the Yaounde central Hospital (Cameroon).
AB  - Heterotopic pregnancy is very rare under natural circumstances. We report the
      case of a 28 year old Gravida2 Para1001 woman at 9 weeks of pregnancy who
      consulted in emergency for acute pelvic pain following metrorrhagia. Physical
      exam revealed hemoperitoneum without shock. An emergency ultrasonography revealed
      two gestational sacs, one intra-uterine and the other extra-uterine. Laparotomy
      was done and the findings were: a ruptured right tubal pregnancy with 1,300
      milliliters of hemoperitoneum, type B left utero-adnexal adhesions and an
      increased uterus consistent with a 9 weeks pregnancy. Right total salpingectomy
      was done and the patient did well postoperatively. That intrauterine pregnancy
      evolved normally under progesterone supply and the woman delivered a termed live
      female baby weighing 3.1 kilogrammes. In our context where ultrasound is not
      always available, practitioners carrying out salpingectomy for ruptured ectopic
      pregnancies should bear in mind the plausibleness of heterotopic pregnancy in
      order to properly handle the uterus. 

PMID- 24876896
TI  - [Hepatic angiomyolipoma].

PMID- 24876897
TI  - [Necrotizing fasciitis of the chest wall complicating an empyema].

PMID- 24876898
TI  - [Skin localization of mantle cell lymphoma].

PMID- 24876899
TI  - Maiden immunization coverage survey in the republic of South Sudan: a cross
      sectional study providing baselines for future performance measurement.
AB  - INTRODUCTION: Since the comprehensive peace agreement was signed in 2005,
      institutionalization of immunization services in South Sudan remained a priority.
      Routine administrative reporting systems were established and showed that
      national coverage rates for DTP-3 rose from 20% in 2002 to 80% in 2011. This
      survey was conducted as part of an overall review of progress in implementation
      of the first EPI Multi-Year Plan for South Sudan 2007-2011. This report provides
      maiden community coverage estimates for immunization. METHODS: A cross sectional
      community survey was conducted between January and May 2012. Ten cluster surveys
      were conducted to generate state-specific coverage estimates. The WHO 30x7
      cluster sampling method was employed. Data was collected using pre-tested,
      interviewer guided, structured questionnaires through house to house visits.
      RESULTS: The fully immunized children were 7.3%. Coverage for specific antigens
      were; BCG (28.3%), DTP-1(25.9%), DTP-3 (22.0%), Measles (16.8%). The drop-out
      rate between the first and third doses of DTP was 21.3%. Immunization coverage
      estimates based on card and history were higher, at 45.7% for DTP-3, 45.8% for
      MCV and 32.2% for full immunization. Majority of immunizations (80.8%) were
      received at health facilities compared to community service points (19.2%). The
      major reason for missed immunizations was inadequate information (41.1%).
      CONCLUSION: The proportion of card-verified, fully vaccinated among children aged
      12-23 months is very low at 7.3%. Future efforts to improve vaccination quality
      and coverage should prioritize training of vaccinators and program communication
      to levels equivalent or higher than investments in EPI cold chain systems since
      2007.

PMID- 24876901
TI  - [Chronic lupus erythematosus: a new etiology of macrocheilia].

PMID- 24876902
TI  - Ovarian pregnancy: a case report in a resource-poor setting.
AB  - Ovarian pregnancy is very rare and to our knowledge, no case has been reported in
      Cameroon. We herein report a case at the Yaounde Central Hospital. It is the case
      of a 29 years old woman who consulted in emergency for left pelvic pain at 9
      weeks of pregnancy. The level of beta human chorionic gonadotropin was 96702
      milli-international Units/ milliliter and ultrasound revealed an intra-ovarian
      gestational sac, an empty uterus and no peritoneal effusion. In the absence of
      facilities for laparoscopy, an emergency laparotomy was done. We found the non
      ruptured mass inside the left ovary. The left fallopian tube, the uterus and the
      right adnexae were normal. We did a successful ovarian dissection and resection
      of gestational sac. Trophoblastic tissue was found at pathology. Similar symptoms
      should draw attention of practitioners on the plausibility of ovarian pregnancy. 

PMID- 24876900
TI  - Evaluation of HIV and AIDS knowledge in rural Cameroon men with the use of a
      questionnaire.
AB  - INTRODUCTION: HIV/AIDS, the most important health problem in Africa, is the
      leading cause of death on the continent. Ignorance on HIV/AIDS status will hamper
      treatment and prevention. To investigate the level of HIV/AIDS knowledge among
      men in a rural area, we performed a questionnaire study on HIV/AIDS knowledge in
      men living in Banga Bakundu, a rural village in Cameroon. METHODS: Forty-eight
      men, aged 17-66 years, were interviewed. They were divided in 2 groups: <= 29
      years, being those young enough to be able to have knowledge about HIV/AIDS at
      the time of their first sexual contact, and those > 29 years who weren't. A semi
      structured clinical interview was performed to obtain information about socio
      demographic characteristics, sexual activity, knowledge about HIV/AIDS and its
      prevention. RESULTS: There is an overall good HIV/AIDS knowledge and what should
      be done about it. Men with a higher level of education and more HIV/AIDS
      knowledge seem to take less preventive measures. The differentiation per age
      group showed that age influenced the data on knowledge and behaviour. CONCLUSION:
      Our data are consistent with other studies. Remarkable is the difference in
      HIV/AIDS knowledge between the 2 age groups, and the relation between HIV/AIDS
      knowledge and sexual habits and prevention. Sufficient HIV/AIDS knowledge did not
      lead to significant changes in sexual behaviour. The questionnaire showed to
      provide sufficient information and was easy to use. Further research should be
      performed.

PMID- 24876904
TI  - [Cutaneous mastocytosis: baby leopard appearance].

PMID- 24876903
TI  - Carcinosarcoma of the corpus uteri (Malignant Mullerian Mixed Tumor): a case
      report in Yaounde (Cameroon).
AB  - Carcinosarcoma of the uterus is a rare tumor representing 2-4% of uterine
      malignancies. Its prognosis is poor with a 5 years survival rate of 10-30%. We
      report a first documented case of carcinosarcoma occurring in a 62 years old
      woman who presented with postmenopausal vaginal bleeding for one year. The
      preoperative biopsy of endometrium revealed a leiomyosarcoma. Total body
      Computerized Tomography (CT) Scan revealed a mass limited to the uterus without
      other abnormalities. We carried out a total abdominal hysterectomy with bilateral
      salpingo-oophorectomy. Post operative histology of the specimen found a
      carcinosarcoma. The patient underwent a course of radiotherapy and a total body
      CT Scan done eight months later revealed no signs of recurrence or metastasis.
      Clinicopathological aspects, treatment options and prognosis of this aggressive
      neoplasm are reviewed. We recommend practitioners to be aware of this lesion for
      an early diagnosis and appropriate treatment. 

PMID- 24876906
TI  - [Aplasia cutis congenita of the vertex in the newborn].

PMID- 24876905
TI  - A case of abdominal textiloma following gynecologic surgery at the Yaounde
      Central Hospital, Cameroon.
AB  - Textiloma is the inadvertent retention of a textile foreign body on the surgical
      site. It is a rare complication of surgery but which carries severe consequences
      for both patients and surgeons in terms of morbi-mortality and medico-legal
      procedures respectively. We herein report the case of an abdominal textiloma in a
      42 year old woman who underwent a total abdominal hysterectomy for symptomatic
      leiomyomas. We also depict the errors that led to this mishap in a tertiary
      hospital in Yaounde (Cameroon). The textiloma was recognized six weeks after the
      causative surgery and removed by laparotomy without further complications. 

PMID- 24876907
TI  - Correlation of transrectal and transabodominal ultrasound measurement of
      transition zone volume with post-operative enucleated adenoma volume in benign
      prostatic hypertrophy.
AB  - INTRODUCTION: Benign prostatic hyperplasia is a common disease of ageing men
      worldwide. Though transrectal ultrasonography (TRUS) is the standard in most
      parts of the world in evaluation of benign prostatic hyperplasia (BPH), it is
      rarely done in some less developed countries because of non availability of
      appropriate probes and or specialists. Transabdominal ultrasonography (TAUS)
      remains the mainstay in these areas. Some controversies still exist in literature
      about the accuracy of TAUS evaluation of prostatic volume in patients with BPH.
      This study aimed at comparing the transition zone volume estimation of the
      prostate on transrectal and transabdominal ultrasound with post-operative
      enucleated adenoma volume in Nigeria patients with BPH and to suggest better
      predictor of prostate volume in evaluation of BPH. METHODS: Forty-six (46)
      patients with lower urinary tract symptoms due to BPH attending the urologic
      clinic were evaluated ultrasonographically and eventually managed with open
      surgery (prostatectomy) after due counselling. The post operative samples were
      weighted using a sensitive top loading weighing balance and converted to volume.
      Since the specific gravity of the prostate is equivalent to that of water,the
      weight is the same as volume. RESULTS: Patients' ages ranged between 59 and 90
      years with a peak age incidence at seventh decade. Transition Zone (TZ) volume
      estimation on both transrectal and transabdominal ultrasound showed positive
      correlation with the post operative enucleated adenoma(r = 0.594, p < 0.001) but
      the transrectal method was more accurate. There was no significant relationship
      between the TZ volume and patients' symptoms(r = 0.491, p = 0.007). CONCLUSION:
      Both TRUS and TAUS are comparable at TZ volume estimation and therefore TAUS can
      be utilized in regions where intracavitary probes and or the expertise is/are not
      available.

PMID- 24876908
TI  - Intraoperative rupture of popliteal artery pseudoaneurysm secondary to distal
      femur osteochondroma: case report and review of the literature.
AB  - Vascular complications from osteochondroma are rare and include essentially
      stenosis, occlusion, and pseudoaneurysms. The authors report an original case of
      intraoperative rupture of undiagnosed popliteal artery pseudoaneurysm during
      resection surgery for a distal femur osteochondroma. 

PMID- 24876910
TI  - The potential protective effect of Physalis peruviana L. against carbon
      tetrachloride-induced hepatotoxicity in rats is mediated by suppression of
      oxidative stress and downregulation of MMP-9 expression.
AB  - The active constituent profile in Cape gooseberry (Physalis peruviana L.) juice
      was determined by GC-MS. Quercetin and kaempferol were active components in the
      juice. In this study we have evaluated its potential protective effect on hepatic
      injury and fibrosis induced by carbon tetrachloride (CCl4). Twenty-eight rats
      divided into 4 groups: Group I served as control group, and Group II received
      weekly i.p. injection of 2 mL CCl4/kg bwt for 12 weeks. Group III were
      supplemented with Physalis juice via the drinking water. The animals of Group IV
      received Physalis juice as Group III and also were intraperitoneally injected
      weekly with 2 mL CCl4/kg bwt for 12 weeks. Hepatoprotective effect was evaluated
      by improvement in liver enzymes serum levels, reduction in collagen areas,
      downregulation in expression of the fibrotic marker MMP-9, reduction in the
      peroxidative marker malonaldehyde and the inflammatory marker nitric oxide, and
      restoration of the activity of antioxidant enzymatic and nonenzymatic systems,
      namely, glutathione content, superoxide dismutase, catalase, glutathione-S
      transferase, glutathione peroxidase, and glutathione reductase activities. The
      results show that the potential hepatoprotective effects of Physalis peruviana
      may be due to physalis acts by promotion of processes that restore hepatolobular
      architecture and through the inhibition of oxidative stress pathway. 

PMID- 24876911
TI  - Evidence of higher oxidative status in depression and anxiety.
AB  - We use a simple method for evaluating antioxidative status, by measuring the
      redox potential of urine, and correlate the findings with measures of anxiety and
      depression. We include 63 individuals (28 males and 35 females aged between 20
      and 65 years). The validated anxiety State-Trait Anxiety Inventory questionnaire
      and the validated BDI (Beck Depression Inventory) questionnaire were used to
      evaluate anxiety and depression. Antioxidative status was determined by measuring
      the redox potential of urine collected in standard conditions. Correlation of the
      antioxidant capacity of urines evaluated using the ferric ion/specific dye method
      or through redox potential using the platinum electrode demonstrated the
      suitability of this last procedure. We found that normal anxiety state values
      corresponded to low urine redox potentials, whereas higher anxiety states were
      associated with high urinary redox potential. We also found that individuals with
      normal BDI values had significantly lower urine redox potentials than individuals
      with higher BDI values. 

PMID- 24876909
TI  - Functional roles of protein nitration in acute and chronic liver diseases.
AB  - Nitric oxide, when combined with superoxide, produces peroxynitrite, which is
      known to be an important mediator for a number of diseases including various
      liver diseases. Peroxynitrite can modify tyrosine residue(s) of many proteins
      resulting in protein nitration, which may alter structure and function of each
      target protein. Various proteomics and immunological methods including mass
      spectrometry combined with both high pressure liquid chromatography and 2D PAGE
      have been employed to identify and characterize nitrated proteins from
      pathological tissue samples to determine their roles. However, these methods
      contain a few technical problems such as low efficiencies with the detection of a
      limited number of nitrated proteins and labor intensiveness. Therefore, a
      systematic approach to efficiently identify nitrated proteins and characterize
      their functional roles is likely to shed new insights into understanding of the
      mechanisms of hepatic disease pathophysiology and subsequent development of new
      therapeutics. The aims of this review are to briefly describe the mechanisms of
      hepatic diseases. In addition, we specifically describe a systematic approach to
      efficiently identify nitrated proteins to study their causal roles or functional
      consequences in promoting acute and chronic liver diseases including alcoholic
      and nonalcoholic fatty liver diseases. We finally discuss translational research
      applications by analyzing nitrated proteins in evaluating the efficacies of
      potentially beneficial agents to prevent or treat various diseases in the liver
      and other tissues. 

PMID- 24876912
TI  - The attenuation of Moutan Cortex on oxidative stress for renal injury in AGEs
      induced mesangial cell dysfunction and streptozotocin-induced diabetic
      nephropathy rats.
AB  - Oxidative stress (OS) has been regarded as one of the major pathogeneses of
      diabetic nephropathy (DN) through damaging kidney which is associated with renal
      cells dysfunction. The aim of this study was to investigate whether Moutan Cortex
      (MC) could protect kidney function against oxidative stress in vitro or in vivo.
      The compounds in MC extract were analyzed by HPLC-ESI-MS. High-glucose-fat diet
      and STZ (30 mg kg(-1)) were used to induce DN rats model, while 200 MUg mL(-1)
      AGEs were for HBZY-1 mesangial cell damage. The treatment with MC could
      significantly increase the activity of SOD, glutathione peroxidase (GSH-PX), and
      catalase (CAT). However, lipid peroxidation malondialdehyde (MDA) was reduced
      markedly in vitro or in vivo. Furthermore, MC decreased markedly the levels of
      blood glucose, serum creatinine, and urine protein in DN rats.
      Immunohistochemical assay showed that MC downregulated significantly transforming
      growth factor beta 2 (TGF-beta2) protein expression in renal tissue. Our data
      provided evidence to support this fact that MC attenuated OS in AGEs-induced
      mesangial cell dysfunction and also in high-glucose-fat diet and STZ-induced DN
      rats. 

PMID- 24876914
TI  - Effects of treating old rats with an aqueous Agaricus blazei extract on oxidative
      and functional parameters of the brain tissue and brain mitochondria.
AB  - Dysfunction of the mitochondrial respiratory chain and increased oxidative stress
      is a striking phenomenon in the brain of aged individuals. For this reason there
      has been a constant search for drugs and natural products able to prevent or at
      least to mitigate these problems. In the present study the effects of an aqueous
      extract of Agaricus blazei, a medicinal mushroom, on the oxidative state and on
      the functionality of mitochondria from the brain of old rats (21 months) were
      conducted. The extract was administered intragastrically during 21 days at doses
      of 200 mg/kg. The administration of the A. blazei extract was protective to the
      brain of old rats against oxidative stress by decreasing the lipid peroxidation
      levels and the reactive oxygen species content and by increasing the nonenzymic
      and enzymic antioxidant capacities. Administration of the A. blazei extract also
      increased the activity of several mitochondrial respiratory enzymes and,
      depending on the substrate, the mitochondrial coupled respiration. 

PMID- 24876915
TI  - Intake of red wine in different meals modulates oxidized LDL level, oxidative and
      inflammatory gene expression in healthy people: a randomized crossover trial.
AB  - Several studies have found that adherence to the Mediterranean Diet, including
      consumption of red wine, is associated with beneficial effects on oxidative and
      inflammatory conditions. We evaluate the outcome of consumption of a McDonald's
      Meal (McD) and a Mediterranean Meal (MM), with and without the additive effect of
      red wine, in order to ascertain whether the addition of the latter has a positive
      impact on oxidized (ox-) LDL and on expression of oxidative and inflammatory
      genes. A total of 24 subjects were analyzed for ox-LDL, CAT, GPX1, SOD2, SIRT2,
      and CCL5 gene expression levels, before and after consumption of the 4 different
      meal combinations with washout intervals between each meal. When red wine is
      associated with McD or MM, values of ox-LDL are lowered (P < 0.05) and expression
      of antioxidant genes is increased, while CCL5 expression is decreased (P < 0.05).
      SIRT2 expression after MM and fasting with red wine is significantly correlated
      with downregulation of CCL5 and upregulation of CAT (P < 0.001). GPX1 increased
      significantly in the comparison between baseline and all conditions with red
      wine. We highlighted for the first time the positive effect of red wine intake
      combined with different but widely consumed meal types on ox-LDL and gene
      expression. Trial Registration. This trial is registered with ClinicalTrials.gov
      NCT01890070. 

PMID- 24876916
TI  - Lipid and protein oxidation in newborn infants after lutein administration.
AB  - OBJECTIVES: To test the hypothesis that neonatal supplementation with lutein in
      the first hours of life reduces neonatal oxidative stress (OS) in the immediate
      postpartum period. METHODS: A randomized controlled, double-blinded clinical
      trial was conducted among 150 newborns divided into control group, not
      supplemented (n = 47), and test group, supplemented with lutein on the first day
      postpartum (n = 103). Blood Samples were collected at birth from cord and at 48
      hrs postpartum while routine neonatal metabolic screenings were taking place.
      Total hydroperoxide (TH), advanced oxidation protein products (AOPP), and
      biological antioxidant potential (BAP) were measured by spectrophotometry and
      data were analyzed by Wilcoxon rank sum test and by multivariate logistic
      regression analysis. RESULTS: Before lutein supplementation, the mean blood
      concentrations of AOPP, TH, and BAP were 36.10 umol/L, 156.75 mmol/H2O2, and
      2361.04 umol/L in the test group. After lutein supplementation, significantly
      higher BAP increment (0.17 +/- 0.22 versus 0.06 versus +/- 0.46) and lower TH
      increment (0.46 +/- 0.54 versus 0.34 +/- 0.52) were observed in the test group
      compared to controls. CONCLUSION: Neonatal supplementation with lutein in the
      first hours of life increases BAP and reduces TH in supplemented babies compared
      to those untreated. The generation of free radical-induced damage at birth is
      reduced by lutein. This trial is registered with ClinicalTrials.gov NCT02068807.

PMID- 24876917
TI  - Multi-detector CT features of acute intestinal ischemia and their prognostic
      correlations.
AB  - Acute intestinal ischemia is an abdominal emergency occurring in nearly 1% of
      patients presenting with acute abdomen. The causes can be occlusive or non
      occlusive. Early diagnosis is important to improve survival rates. In most cases
      of late or missed diagnosis, the mortality rate from intestinal infarction is
      very high, with a reported value ranging from 60% to 90%. Multi-detector computed
      tomography (MDCT) is a fundamental imaging technique that must be promptly
      performed in all patients with suspected bowel ischemia. Thanks to the new
      dedicated reconstruction program, its diagnostic potential is much improved
      compared to the past and currently it is superior to that of any other
      noninvasive technique. The increased spatial and temporal resolution, high
      quality multi-planar reconstructions, maximum intensity projections, vessel
      probe, surface-shaded volume rending and tissue transition projections make MDCT
      the gold standard for the diagnosis of intestinal ischemia, with reported
      sensitivity, specificity, positive and negative predictive values of 64%-93%, 92%
      100%, 90%-100% and 94%-98%, respectively. MDCT contributes to appropriate
      treatment planning and provides important prognostic information thanks to its
      ability to define the nature and extent of the disease. The purpose of this
      review is to examine the diagnostic and prognostic role of MDCT in bowel ischemia
      with special regard to the state of art new reconstruction software. 

PMID- 24876918
TI  - Use of cone beam computed tomography in periodontology.
AB  - Diagnosis of periodontal disease mainly depends on clinical signs and symptoms.
      However, in the case of bone destruction, radiographs are valuable diagnostic
      tools as an adjunct to the clinical examination. Two dimensional periapical and
      panoramic radiographs are routinely used for diagnosing periodontal bone levels.
      In two dimensional imaging, evaluation of bone craters, lamina dura and
      periodontal bone level is limited by projection geometry and superpositions of
      adjacent anatomical structures. Those limitations of 2D radiographs can be
      eliminated by three-dimensional imaging techniques such as computed tomography.
      Cone beam computed tomography (CBCT) generates 3D volumetric images and is also
      commonly used in dentistry. All CBCT units provide axial, coronal and sagittal
      multi-planar reconstructed images without magnification. Also, panoramic images
      without distortion and magnification can be generated with curved planar
      reformation. CBCT displays 3D images that are necessary for the diagnosis of
      intra bony defects, furcation involvements and buccal/lingual bone destructions.
      CBCT applications provide obvious benefits in periodontics, however; it should be
      used only in correct indications considering the necessity and the potential
      hazards of the examination. 

PMID- 24876919
TI  - Coronary plaque imaging by coronary computed tomography angiography.
AB  - Coronary computed tomography angiography (CTA) has become the useful noninvasive
      imaging modality alternative to the invasive coronary angiography for detecting
      coronary artery stenoses in patients with suspected coronary artery disease
      (CAD). With the development of technical aspects of coronary CTA, clinical
      practice and research are increasingly shifting toward defining the clinical
      implication of plaque morphology and patients outcomes by coronary CTA. In this
      review we discuss the coronary plaque morphology estimated by CTA beyond coronary
      angiography including the comparison to the currently available other imaging
      modalities used to examine morphological characteristics of the atherosclerotic
      plaque. Furthermore, this review underlies the value of a combined assessment of
      coronary anatomy and myocardial perfusion in patients with CAD, and adds to an
      increasing body of evidence suggesting an added diagnostic value when combining
      both modalities. We hope that an integrated, multi-modality imaging approach will
      become the gold standard for noninvasive evaluation of coronary plaque morphology
      and outcome data in clinical practice. 

PMID- 24876920
TI  - Partial splenic artery embolization in cirrhotic patients.
AB  - Splenomegaly is a common sequela of cirrhosis, and is frequently associated with
      decreased hematologic indices including thrombocytopenia and leukopenia. Partial
      splenic artery embolization (PSE) has been demonstrated to effectively increase
      hematologic indices in cirrhotic patients with splenomegaly. This is particularly
      valuable amongst those cirrhotic patients who are not viable candidates for
      splenectomy. Although PSE was originally developed decades ago, it has recently
      received increased attention. Presently, PSE is being utilized to address a
      number of clinical concerns in the setting of cirrhosis, including: decreased
      hematologic indices, portal hypertension and its associated sequela, and splenic
      artery steal syndrome. Following PSE patients demonstrate significant increases
      in platelets and leukocytes. Though progressive decline of hematologic indices
      occur following PSE, they remain improved as compared to pre-procedural values
      over long-term follow-up. PSE, however, is not without risk and complications of
      the procedure may occur. The most common complication of PSE is post-embolization
      syndrome, which involves a constellation of symptoms including fever, pain, and
      nausea/vomiting. The rate of complications has been shown to increase as the
      percent of total splenic volume embolized increases. The purpose of this review
      is to explore the current literature in regards to PSE in cirrhotic patients and
      to highlight their techniques, and statistically summarize their results and
      associated complications. 

PMID- 24876921
TI  - Unusual fistulas and connections in the cardiovascular system: A pictorial
      review.
AB  - A fistula is an abnormal vascular connection leading to diversion of blood from a
      high resistance arterial circuit to low resistance venous circuit. Coronary
      artery fistulas are abnormal communications of the coronary artery with a chamber
      of the heart, or with any segment of systemic or pulmonary circulation, bypassing
      the myocardial capillaries. Other unusual fistulas include connection between
      aorta and the right atrium/superior vena cava, aorta and the inferior vena cava
      or between a coronary artery bypass graft and a cardiac vein. Abnormal
      connections also include origin of the coronary artery from the pulmonary artery.
      In this article, we review the imaging, particularly computed tomography and
      magnetic resonance imaging of unusual fistulas and connections involving the
      cardiovascular system, particularly the coronary arteries and the aorta. 

PMID- 24876913
TI  - Oxidative stress and mitochondrial dysfunction across broad-ranging pathologies:
      toward mitochondria-targeted clinical strategies.
AB  - Beyond the disorders recognized as mitochondrial diseases, abnormalities in
      function and/or ultrastructure of mitochondria have been reported in several
      unrelated pathologies. These encompass ageing, malformations, and a number of
      genetic or acquired diseases, as diabetes and cardiologic, haematologic, organ
      specific (e.g., eye or liver), neurologic and psychiatric, autoimmune, and
      dermatologic disorders. The mechanistic grounds for mitochondrial dysfunction
      (MDF) along with the occurrence of oxidative stress (OS) have been investigated
      within the pathogenesis of individual disorders or in groups of interrelated
      disorders. We attempt to review broad-ranging pathologies that involve
      mitochondrial-specific deficiencies or rely on cytosol-derived prooxidant states
      or on autoimmune-induced mitochondrial damage. The established knowledge in these
      subjects warrants studies aimed at elucidating several open questions that are
      highlighted in the present review. The relevance of OS and MDF in different
      pathologies may establish the grounds for chemoprevention trials aimed at
      compensating OS/MDF by means of antioxidants and mitochondrial nutrients. 

PMID- 24876922
TI  - Role of (18)F-FDG PET/CT in pre and post treatment evaluation in head and neck
      carcinoma.
AB  - Head and neck cancer (HNC) ranks as the 6(th) most common cancer worldwide, with
      the vast majority being head and neck squamous cell carcinoma (HNSCC). The
      majority of patients present with complicated locally advanced disease (typically
      stage III and IV) requiring multidisciplinary treatment plans with combinations
      of surgery, radiation therapy and chemotherapy. Tumor staging is critical to
      decide therapeutic planning. Multiple challenges include accurate tumor
      localization with precise delineation of tumor volume, cervical lymph node
      staging, detection of distant metastasis as well as ruling out synchronous second
      primary tumors. Some patients present with cervical lymph node metastasis without
      obvious primary tumors on clinical examination or conventional cross sectional
      imaging. Treatment planning includes surgery, radiation, chemotherapy or
      combinations that could significantly alter the anatomy and physiology of this
      complex head and neck region, making assessment of treatment response and
      detection of residual/ recurrent tumor very difficult by clinical evaluation and
      computed tomography (CT) or magnetic resonance imaging (MRI). (18)F-2-fluoro-2
      deoxy-D-glucose positron emission tomography/CT ((18)F-FDG PET/CT) has been
      widely used to assess HNC for more than a decade with high diagnostic accuracy
      especially in detection of initial distant metastasis and evaluation of treatment
      response. There are some limitations that are unique to PET/CT including
      artifacts, lower soft tissue contrast and resolution as compared to MRI, false
      positivity in post-treatment phase due to inflammation and granulation tissues,
      etc. The aim of this article is to review the roles of PET/CT in both pre and
      post treatment management of HNSCC including its limitations that radiologists
      must know. Accurate PET/CT interpretation is the crucial initial step that leads
      to appropriate tumor staging and treatment planning. 

PMID- 24876923
TI  - Atherosclerosis imaging using 3D black blood TSE SPACE vs 2D TSE.
AB  - AIM: To compare 3D Black Blood turbo spin echo (TSE) sampling perfection with
      application-optimized contrast using different flip angle evolution (SPACE) vs 2D
      TSE in evaluating atherosclerotic plaques in multiple vascular territories.
      METHODS: The carotid, aortic, and femoral arterial walls of 16 patients at risk
      for cardiovascular or atherosclerotic disease were studied using both 3D black
      blood magnetic resonance imaging SPACE and conventional 2D multi-contrast TSE
      sequences using a consolidated imaging approach in the same imaging session.
      Qualitative and quantitative analyses were performed on the images. Agreement of
      morphometric measurements between the two imaging sequences was assessed using a
      two-sample t-test, calculation of the intra-class correlation coefficient and by
      the method of linear regression and Bland-Altman analyses. RESULTS: No
      statistically significant qualitative differences were found between the 3D SPACE
      and 2D TSE techniques for images of the carotids and aorta. For images of the
      femoral arteries, however, there were statistically significant differences in
      all four qualitative scores between the two techniques. Using the current
      approach, 3D SPACE is suboptimal for femoral imaging. However, this may be due to
      coils not being optimized for femoral imaging. Quantitatively, in our study,
      higher mean total vessel area measurements for the 3D SPACE technique across all
      three vascular beds were observed. No significant differences in lumen area for
      both the right and left carotids were observed between the two techniques.
      Overall, a significant-correlation existed between measures obtained between the
      two approaches. CONCLUSION: Qualitative and quantitative measurements between 3D
      SPACE and 2D TSE techniques are comparable. 3D-SPACE may be a feasible approach
      in the evaluation of cardiovascular patients.

PMID- 24876924
TI  - Comparison of different magnetic resonance imaging sequences for assessment of
      fistula-in-ano.
AB  - AIM: To assess agreement between different forms of T2 weighted imaging (T2WI),
      and post-contrast T1WI in the depiction of fistula tracts, inflammation, and
      internal openings with that of a reference test. METHODS: Thirty-nine consecutive
      prospective cases were enrolled. The following sequences were used for T2WI: 2D
      turbo-spin-echo (2D T2 TSE); 3D T2 TSE; short tau inversion recovery (STIR); 2D
      T2 TSE with fat saturation performed in all patients. T1WI were either a 3D T1
      weighted prepared gradient echo sequence with fat saturation or a 2D T1 fat
      saturation [Spectral presaturation with inversion (SPIR)]. Agreement for each
      sequence for determination of fistula extension, internal openings, and the
      presence of active inflammation was assessed separately and blindly against a
      reference test comprised of follow-up, surgery, endoscopic ultrasound, and
      assessment by an independent experienced radiologist with access to all images.
      RESULTS: Fifty-six fistula tracts were found: 2 inter-sphincteric, 13 trans
      sphincteric, and 24 with additional tracts. The best T2 weighted sequence for
      depiction of fistula tracts was 2D T2 TSE (Cohen's kappa = 1.0), followed by 3D
      T2 TSE (0.88), T2 with fat saturation (0.54), and STIR (0.19). Internal openings
      were best seen on 2D T2 TSE (Cohen's kappa = 0.88), followed by 3D T2 TSE (0.70),
      T2 with fat saturation (0.54), and STIR (0.31). Detection of inflammation showed
      Cohen's kappa of 0.88 with 2D T2 TSE, 0.62 with 3D T2 TSE, 0.63 with STIR, and
      0.54 with T2 with fat saturation. STIR, 3D T2 TSE, and T2 with fat saturation did
      not make any contributions compared to 2D T2 TSE. Post-contrast 3D T1 weighted
      prepared gradient echo sequence with fat saturation showed better agreement in
      the depiction of fistulae (Cohen's kappa = 0.94), finding internal openings
      (Cohen's kappa = 0.97), and evaluating inflammation (Cohen's kappa = 0.94)
      compared to post-contrast 2D T1 fat saturation or SPIR where the corresponding
      figures were 0.71, 0.66, and 0.87, respectively. Comparing the best T1 and T2
      sequences showed that, for best results, both sequences were necessary.
      CONCLUSION: 3D T1 weighted sequences were best for the depiction of internal
      openings and active inflammatory components, while 2D T2 TSE provided the best
      assessment of fistula extension.

PMID- 24876925
TI  - Size-specific dose estimates: Localizer or transverse abdominal computed
      tomography images?
AB  - AIM: To investigate effect of body dimensions obtained from localizer radiograph
      and transverse abdominal computed tomography (CT) images on Size Specific Dose
      Estimate. METHODS: This study was approved by Institutional Review Board and was
      compliant with Health Insurance Portability and Accountability Act. Fifty
      patients with abdominal CT examinations (58 +/- 13 years, Male:Female 28:22) were
      included in this study. Anterior-posterior (AP) and lateral (Lat) diameters were
      measured at 5 cm intervals from the CT exam localizer radiograph (simple X-ray
      image acquired for planning the CT exam before starting the scan) and transverse
      CT images. Average of measured AP and Lat diameters, as well as maximum, minimum
      and mid location AP and Lat were measured on both image sets. In addition, off
      centering of patients from the gantry iso-center was calculated from the
      localizers. Conversion factors from American Association of Physicists in
      Medicine (AAPM) report 204 were obtained for AP, Lat, AP + Lat, and effective
      diameter (? AP * Lat) to determine size specific dose estimate (SSDE) from the CT
      dose index volume (CTDIvol) recorded from the dose reports. Data were analyzed
      using SPSS v19. RESULTS: Total number of 5376 measurements was done. In some
      patients entire body circumference was not covered on either projection
      radiograph or transverse CT images; hence accurate measurement of AP and Lat
      diameters was not possible in 11% (278/2488) of locations. Forty one patients
      were off-centered with mean of 1.9 +/- 1.8 cm (range: 0.4-7 cm). Conversion
      factors for attained diameters were not listed on AAPM look-up tables in 3%
      (80/2488) of measurements. SSDE values were significantly different compared to
      CTDIvol, ranging from 32% lower to 74% greater than CTDIvol. CONCLUSION: There is
      underestimation and overestimation of dose comparing SSDE values to CTDIvol.
      Localizer radiographs are associated with overestimation of patient size and
      therefore underestimation of SSDE.

PMID- 24876926
TI  - Factors influencing the yield of mesenteric angiography in lower gastrointestinal
      bleed.
AB  - AIM: To assess if certain triaging rules could be established to optimize the
      yield of mesenteric angiography. METHODS: Medical records of 101 patients were
      retrospectively reviewed and parameters relating to age, gender, pulse rate,
      blood pressure, serum hemoglobin, intensive care unit (ICU) admission, and the
      number of packed red blood cells (PRBC) transfused in the 12 and 24 h prior to
      the angiography were tabulated in two groups with positive and negative
      angiography results. RESULTS: We found no correlation between gender, pulse rate,
      blood pressure or serum hemoglobin and positivity of the mesenteric angiogram.
      But patients with positive angiogram were found to be on average 7 years older
      (73.2 years vs 65.9 years old) (P = 0.02). Angiogram was positive in 39.3 %
      (11/28) of patients admitted in ICU vs 23.2% (17/73) who were admitted elsewhere
      in the hospital (P = 0.03). In the 12 and 24 h prior to angiography, patients
      with a positive angiogram received a mean of 2.7 +/- 2.3 and 3.3 +/- 2.6 units of
      PRBC s respectively, while patients with a negative angiogram had a mean of 1.6
      +/- 1.9 (P = 0.02) and 2.1 +/- 2.6 units (P = 0.04) received respectively in the
      same period. CONCLUSION: Older age, ICU admission, having received at least 4
      units PRBC over 12 h or 5 units over 24 h prior to angiogram are leading
      indicators for a positive study.

PMID- 24876927
TI  - Mitochondrial fusion protein MFN2 interacts with the mitostatin-related protein
      MNS1 required for mouse sperm flagellar structure and function.
AB  - BACKGROUND: Cilia and the sperm flagellum share many structural properties.
      Meiosis-specific nuclear structural 1 (MNS1) is a recently characterized protein
      that is abundantly expressed in post-meiotic spermatids and is required for
      proper flagellar and motile cilia formation. To explore the possible functions of
      MNS1, we performed a BLAST search and determined it is homologous to the
      conserved domain pfam13868, exemplified by mitostatin. This protein interacts
      with mitofusin 2 (MFN2), a protein that participates in regulating mitochondrial
      associations to subcellular organelles. We hypothesized that an association
      between MFN2 and MNS1 in the sperm is involved in flagellar biogenesis and
      function. RESULTS: In the studies reported here, MFN2 was found in murine
      reproductive and somatic tissues high in ciliary content while MNS1 was present
      as two closely migrating bands in reproductive tissues. Interestingly, mitostatin
      was also present in reproductive tissues. Similar to Mns1 and mitostatin, Mfn2
      was expressed in the testis as detected by RT-PCR. In addition, Mfn2 and Mns1
      decreased in expression from pachytene spermatocytes to condensing spermatids as
      assessed by quantitative RT-PCR. Co-immunoprecipitation demonstrated an
      association between MFN2 and MNS1 in spermatogenic cells. Indirect
      immunofluorescence indicated that MFN2 and MNS1 co-localized to the sperm
      flagellum in freshly collected cauda epididymal sperm. MFN2 associated with the
      midpiece while MNS1 was present throughout the sperm tail in caput and cauda
      epididymal sperm. In spermatogenic cells, MFN2 was seen in the mitochondria, and
      MNS1 was present throughout the cell cytoplasm. MFN2 and MNS1 were present in
      detergent-resistant flagellar structures of the sperm. CONCLUSIONS: These results
      demonstrate that MFN2 and MNS1 are present in spermatogenic cells and are an
      integral part of the sperm flagellum, indicating they play a role in flagellar
      biogenesis and/or function.

PMID- 24876929
TI  - Lessons from next-generation sequencing in genetic skeletal disorders.

PMID- 24876928
TI  - Osteoimmunology: oncostatin M as a pleiotropic regulator of bone formation and
      resorption in health and disease.
AB  - Bone remodeling in health and disease is carried out by osteoblasts and
      osteoclasts, which respectively produce bone matrix and resorb it. Endocrine and
      paracrine control of these cells can be direct, but they are also exerted
      indirectly, either by influencing progenitor cell differentiation or by
      stimulating paracrine signals from local accessory cells including osteocytes
      (which form a critical communication and regulation network within the bone
      matrix), macrophages and T lymphocytes. Here we review the osteotropic actions of
      the interleukin-6 family member cytokine oncostatin M (OSM), which is of
      particular interest because of its ability to stimulate bone accrual. OSM is
      produced within the bone microenvironment by cells of both mesenchymal and
      hematopoietic origin, including osteocytes, osteoblasts, macrophages and T
      lymphocytes, and can act via two receptor complexes: OSM receptor:gp130 and
      leukemia inhibitory factor receptor (LIFR):gp130. Although OSM can directly
      stimulate osteoblast mineralization activity and differentiation, it can also
      stimulate mesenchymal stem cell osteoblastic commitment at the expense of
      adipogenesis. In osteocytes, OSM can suppress the production of the bone
      formation inhibitor sclerostin, an action that is mediated by LIFR:gp130. OSM
      also stimulates the production of receptor activator of nuclear factor kappaB
      ligand by osteoblasts and thereby drives the formation of osteoclasts
      particularly in pathological conditions. Thus, cellular effects of OSM on bone
      metabolism include direct and indirect actions mediated by two related
      receptor/ligand complexes. OSM therefore provides an example of paracrine and
      endocrine control mechanisms that regulate bone mass by controlling both bone
      formation and resorption. 

PMID- 24876931
TI  - Sensitivity of osteoporosis screening guidelines for eventual hip fracture in
      older male veterans.
AB  - This study sought to determine whether guideline-recommended clinical criteria to
      select men for osteoporosis screening provide significantly better sensitivity
      than the osteoporotic screening tool (OST) among men who later went on to have a
      hip fracture, and whether the sensitivity differs by race. This retrospective
      observational study uses data from the Department of Veterans Affairs Austin
      Automation Center. We identified 825 male veterans with hip fractures from 2007
      to 2009. Clinical risk factors used as screening selection criteria were
      abstracted from five accepted guidelines. Outpatient encounters were examined for
      each subject to determine whether they would have met screening selection
      criteria for each guideline in the 5 years before their hip fracture event.
      Sensitivities for each guideline were compared with the OST, using McNemar's
      exact test. Sensitivities of Veterans Affairs Health Service Research and
      Development Services (VA HSR&D) and National Osteoporosis Foundation (NOF)
      guidelines were 77% and 82%, respectively, and were significantly better than the
      OST sensitivity of 72% (P<0.05). Sensitivities of American College of Physicians
      (ACP; 68%), VA Secretary's Letters (45%) and Center for Medicare and Medicaid
      Services (13%) were significantly worse than the OST sensitivity (P<0.001). The
      sensitivities of the VA HSR&D, ACP and NOF were significantly higher in Whites
      compared with non-Whites (76% vs 65%, P<0.01; 70% vs 58%, P<0.01; and 84% vs 70%,
      P<0.001, respectively). Only VA HSR&D and NOF clinical screening criteria are
      more sensitive than OST in identifying veterans who subsequently experience hip
      fractures, and these sensitivities vary by race. 

PMID- 24876932
TI  - Oily wastewaters treatment using Pseudomonas sp. isolated from the compost
      fertilizer.
AB  - BACKGROUND: Discharging the oily wastewater in the environment causes serious
      problems, because of the oil compounds and organic materials presence. Applying
      biological methods using the lipase enzyme producer microorganisms can be an
      appropriate choice for treatment of these wastewaters. The aim of this study is
      to treat those oil wastewaters having high concentration of oil by applying
      lipase enzyme producer bacteria. MATERIALS AND METHODS: Oil concentration
      measurement was conducted using the standard method of gravimetric and the
      wastewater under study was synthetically made and contained olive, canola and
      sunflower oil. The strain used in this study was Pseudomonas strain isolated from
      compost fertilizer. The oil under study had concentration of 1.5 to 22 g/l.
      RESULTS: The oil removal amount in concentrations lower than 8.4 g/l was over 95
      +/- 1.5%. Increase of the oil's concentration to 22 g/l decreases the amount of
      removal in retention time of 44 hours to 85 +/- 2.5%. The best yield of removing
      this strain in retention time of 44 hours and temperature of 30 degrees C was
      achieved using Ammonium Nitrate as the nitrogen resource which yield was about 95
      percent. CONCLUSION: The findings of the research showed that Pseudomonas
      bacteria isolated from the compost fertilizer can degrade high concentration
      oils.

PMID- 24876930
TI  - Bisphosphonates and bone quality.
AB  - Bisphosphonates (BPs) are bone-avid compounds used as first-line medications for
      the prevention and treatment of osteoporosis. They are also used in other
      skeletal pathologies such as Paget's and metastatic bone disease. They
      effectively reduce osteoclast viability and also activity in the resorptive phase
      of bone remodelling and help preserve bone micro-architecture, both major
      determinants of bone strength and ultimately of the susceptibility to fractures.
      The chemically distinctive structure of each BP used in the clinic determines
      their unique affinity, distribution/penetration throughout the bone and their
      individual effects on bone geometry, micro-architecture and composition or what
      we call 'bone quality'. BPs have no clinically significant anabolic effects. This
      review will touch upon some of the components of bone quality that could be
      affected by the administration of BPs. 

PMID- 24876933
TI  - Esophageal cancer: staging system and guidelines for staging and treatment.
AB  - Survival of esophageal cancer is improving but remains poor. Esophageal cancer
      stage is based on depth of tumor invasion, involvement of regional lymph nodes,
      and the presence or absence of metastatic disease. Appropriate work-up is
      critical to identify accurate pre-treatment staging so that both under-treatment
      and unnecessary treatment is avoided. Treatment strategy should follow guideline
      recommendations, and generally should be developed after multidisciplinary
      evaluation. 

PMID- 24876934
TI  - Endoscopic therapies for Barrett's neoplasia.
AB  - The standard of care for treatment of Barrett's esophagus (BE) with early
      esophageal neoplasia, including high-grade dysplasia (HGD) and intramucosal
      adenocarcinoma (IMC), has undergone a revolution over the past several years.
      With the introduction and popularization of endoscopic ablative technologies,
      along with the refinement of endoscopic mucosal resection (EMR) techniques, the
      majority of cases of early neoplasia in the setting of BE now are managed by
      endoscopic approaches. As a result, many patients who previously would have been
      referred for esophagectomy now may be spared from this major surgical procedure
      with its inherent morbidity, potential for mortality, and negative impact on long
      term gastrointestinal function. The esophageal surgeon must be knowledgeable
      about the indications for such endoscopic therapies, as well as their limitations
      and potential pitfalls, so as to apply them in the appropriate clinical
      scenarios. 

PMID- 24876935
TI  - The role of induction therapy.
AB  - The incidence of esophageal cancer has been steadily increasing. The 5-year
      survival of esophageal cancer has minimally improved over the past 30 years. In
      this article, we review the management of esophageal cancer, focusing on the
      literature investigating the role of induction chemotherapy and radiation
      therapy. 

PMID- 24876936
TI  - Minimally invasive and robotic Ivor Lewis esophagectomy.
AB  - Esophageal cancer is the eighth most common malignancy and the sixth most common
      cause of cancer-related death worldwide. Esophagectomy provides a curative
      treatment but carries significant morbidity and mortality. Ivor Lewis
      esophagectomy (ILE) is one of the most commonly employed open techniques of
      esophagectomy. Minimally invasive approaches have been explored in ILE in an
      effort to reduce operative morbidity. This article reviews recent literature of
      minimally invasive Ivor Lewis esophagectomy (MI-ILE), discusses its clinical
      outcomes, and introduces the robotic approach in MI-ILE. MI-ILE has demonstrated
      comparable postoperative outcomes to open ILE, and it has shown potential to
      reduce blood loss and length of hospitalization. Due to limited studies, no
      significant improvement of long-term survival has been reported in MI-ILE.
      Robotic ILE is safe and feasible, but more studies are needed to prove
      identifiable benefits. Randomized controlled trials comparing MI-ILE or robotic
      ILE with conventional open ILE are warranted to determine the optimal surgical
      procedure for the treatment of esophageal cancer. 

PMID- 24876937
TI  - Mckeown esophagogastrectomy.
AB  - Esophageal cancer is increasing in incidence faster than other cancers in the US.
      Outcomes after esophagectomy may be related to many factors, including the age of
      the patient, the stage of the tumor, the operative approach, and the incidence of
      postoperative morbidity. Pulmonary complications are the major source of
      morbidity and mortality following esophageal resection, and numerous studies have
      identified various factors associated with these complications. Various operative
      approaches have been applied to the management of esophageal cancer, with the
      goal of optimal oncologic results with the lowest possible morbidity and
      mortality. The McKeown esophagogastrectomy is applicable for most patients with
      esophageal cancer, and the technique and results are reviewed. 

PMID- 24876938
TI  - Extent of lymph node dissection: common hepatic artery lymph node dissection can
      be omitted for esophageal squamous cell carcinoma.
AB  - OBJECTIVES: Controversy persists regarding the adequate extent of lymph node (LN)
      dissection in thoracic esophageal cancer (EC) surgery. Oncologic efficacy should
      be balanced with the increased risk of postoperative complications after
      aggressive radical LN dissection. Here, we evaluate the effectiveness of common
      hepatic artery LN dissection in surgery for thoracic esophageal squamous cell
      carcinoma. PATIENTS AND METHODS: Among a total of 1,563 EC patients who underwent
      surgery from May 2005 to December 2012 at the Fudan University Shanghai Cancer
      Center, 1,248 thoracic esophageal squamous cell carcinoma were selected for this
      study, including 682 patients who underwent esophagectomy with common hepatic
      artery LN dissection and 566 patients who underwent esophagectomy without common
      hepatic artery LN dissection. The clinical data of patients were retrospectively
      analyzed. In addition, the locoregional LN metastasis, relationship between
      metastatic rates of common hepatic artery LN and clinicopathological factors were
      analyzed. A propensity score match analysis were performed to control for
      potential differences in the characteristics of patients with EC cell carcinoma,
      and postoperative complications were analyzed after propensity score-matching.
      RESULTS: The metastatic rate of common hepatic LN was 3.5%. Logistic regression
      analysis revealed tumor diameter, N classification and pTNM stage were risk
      factors for common hepatic LN metastasis. Matching based on propensity scores
      produced 361 patients in each group. The overall incidence of postoperative
      complications was 32.70% and 35.45%, respectively, no significant difference was
      found (P=0.432). CONCLUSIONS: The metastatic rate of common hepatic artery LN is
      low. For patients who undergo resection for Stage I thoracic esophageal squamous
      cell carcinoma, the dissection of common hepatic artery LN may be safely omitted.

PMID- 24876939
TI  - Jejunal graft conduits after esophagectomy.
AB  - INTRODUCTION: The jejunum is uniquely suitable for esophageal reconstruction
      because it is relatively abundant, does not require a formal preparation, is
      typically free of disease, has similar luminal size compared to the esophagus,
      has intrinsic peristalsis, and may not undergo senescent lengthening to the
      extent that colon does. METHODS: To obtain data to determine the outcomes of
      jejunal interposition for esophageal replacement, electronic databases were
      searched, including MEDLINE (Ovid SP), Scopus, EMBASE (Ovid SP), Science Direct's
      full-text database, and the Cochrane Library from January 1990 to September 2013.
      RESULTS: Two-hundred and forty-six abstracts were reviewed and an article search
      was performed on selected abstracts. Additional references from article
      bibliographies were included as appropriate. A thorough search of the literature
      demonstrates the widespread use of jejunum, either as a free, pedicled, or free-
      and pedicled-graft with acceptable results. CONCLUSIONS: Any region of the
      esophagus can be replaced by jejunum, whether it is distal esophagus as a
      Merendino procedure for a vagal-sparing esophagectomy and segmental jejunal
      reconstruction connected to stomach, mid-thoracic esophagus as a pedicled jejunal
      interposition or free flap, cervical esophagus as a free segmental interposition,
      or the entire length as a long-segment super-charged pedicled jejunal
      interposition. When used, the jejunum is either pedicled, augmented ("super
      charged"), a free segment (requiring microvascular anastomosis of artery and
      vein), or a combination of the above.

PMID- 24876940
TI  - Salvage esophagectomy.
AB  - Patients with locally advanced esophageal cancer are treated with definitive
      chemoradiation (dCXRT) for a number of reasons. Some patients are never referred
      to a surgeon for a con-versation about surgery, others decline surgery, and some
      are not candidates for surgery due to a sag in performance status secondary to
      therapy. Regardless of method of arrival at dCXRT, the risk of local/regional
      recurrence during follow-up is significant. Many of these patients are faced with
      limited options for therapy once dCXRT has failed. Salvage esoph-agectomy has
      historically been considered a morbid procedure and poor choice for lo
      cal/regional recurrence. This chapter reviews the recent literature arguing the
      relevance of salvage resection. We recommend that any patient suffering from
      persistent or recurrent lo-cal/regional only disease after dCXRT should be
      referred to an experienced esophageal center to consider surgical options. 

PMID- 24876942
TI  - Managing complications I: leaks, strictures, emptying, reflux, chylothorax.
AB  - Esophagectomy can be used to treat several esophageal diseases; it is most
      commonly used for treatment of esophageal cancer. Esophagectomy is a major
      procedure that may result in various complications. This article reviews only the
      important complications resulting from esophageal resection, which are
      anastomotic complications after esophageal reconstruction (leakage and
      stricture), delayed emptying or dumping syndrome, reflux, and chylothorax. 

PMID- 24876941
TI  - Cervical triangulating stapled anastomosis: technique and initial experience.
AB  - OBJECTIVE: To explore the safety and efficacy of modified cervical triangulating
      stapled anastomosis (TSA) for gastroesophageal anastomosis (GEA) in minimally
      invasive esophagectomy (MIE). METHODS: From January 2013 to November 2013, eighty
      four patients who underwent three-stage MIE was enrolled. During the cervical
      stage, either circular stapled (CS) or triangulating stapled (TS) anastomosis was
      applied for GEA. Clinical features were collected and compared to identify the
      differences between the two groups. RESULTS: A total of 84 patients were included
      in this study. The clinical characteristics were close between the two groups.
      Intra-operatively, the duration of GEA was close between the two groups (18+/-3.4
      vs. 17+/-2.7 min, P=0.139). Post-operatively, Cervical anastomotic leakage
      occurred in one (3.0%) of the 33 TS patients, but in six (11.8%) of the 51 CS
      patients (P=0.312). The incidence of anastomotic stenosis was 0.0% and 13.7% in
      the TS and CS groups, respectively (P=0.069). The overall incidence of
      postoperative complications was significantly lower in TS than that in CS (15.2%
      vs. 35.3%, P=0.043). There was no difference in the median length of hospital
      stay or perioperative mortality rate between the two groups. CONCLUSIONS: TSA is
      a safe and effective alternative for GEA, which would probably lower the
      incidence of leakage and stenosis following MIE. Further studies based on larger
      volumes are required to confirm these findings.

PMID- 24876943
TI  - Managing complications II: conduit failure and conduit airway fistulas.
AB  - Conduit failure and conduit airway fistula are rare complications after
      esophagectomy, however they can be catastrophic resulting in high mortality.
      Survivors can expect a prolonged hospital course with multiple interventions and
      an extended period of time prior to being able to resume oral nutrition. High
      index of suspicion can aid in early diagnosis. Conduit failure usually requires a
      period of proximal esophageal diversion and staged reconstruction. Conduit airway
      fistulas may be amenable to endoscopic repair but this has a high failure rate
      and many patients will require surgical repair with closure of the fistula and
      interposition of vascularized tissue to minimize recurrence. 

PMID- 24876944
TI  - PCR-Based Detection of Babesia ovis in Rhipicephalus bursa and Small Ruminants.
AB  - This study aimed to assess the prevalence of Babesia ovis infection in adult
      Rhipicephalus bursa and small ruminants in West Azerbaijan province, Iran. Blood
      samples were collected from 280 sheep and 122 goats of forty randomly selected
      flocks. Specific B. ovis fragment was detected in 67 animals (16.7%), of which 52
      animals (18.6%) were sheep and 15 animals (12.2%) goats (P < 0.05). Of the 848 R.
      bursa collected from naturally infested small ruminants and farm dogs, Babesia
      ovis was detected by PCR in salivary glands of 94 adult ticks. The frequency of
      B. ovis infection was higher in flocks with tick in comparison with animals
      without tick (P < 0.05). Positive amplification from blood of ruminants, ticks,
      oviposition ticks, eggs, and larvae was subjected to restriction digestion with
      HphI. One RFLP profile was produced. The PCR-RFLP results indicated that one
      strain of B. ovis exists in this area. The results showed that the PCR was useful
      method to investigate the epidemiology of small ruminants' babesiosis.
      Furthermore, R. Bursa, which can transovarially transmit B. ovis and as well as
      being widely distributed in West Azerbaijan province, Iran, might play an
      important role in the field as a natural vector of B. ovis. 

PMID- 24876945
TI  - Association of Maternal Age to Development and Progression of Retinopathy of
      Prematurity in Infants of Gestational Age under 33 Weeks.
AB  - Aim. To find predictive and indicative markers of risk for development of
      retinopathy of prematurity (ROP) and its progression to the stage requiring laser
      treatment, in premature infants whose gestational age (GA) was under 33 weeks.
      Methods. We retrospectively reviewed medical records of 197 premature infants
      born in 2005-2010 whose GA < 33 weeks and underwent eye screening at Keio
      University Hospital. The association between candidate risk factors and
      development or progression of ROP was assessed. Results. Among the 182 eligible
      infants (median GA, 29.1 weeks; median birth weight (BW), 1028 g), 84 (46%)
      developed any stage of ROP, of which 45 (25%) required laser treatment.
      Multivariate analysis using a stepwise method showed that GA (P = 0.002; 95%
      confidence interval (CI), 0.508-0.858), BW (P < 0.001; 95% CI, 0.994-0.998), and
      lower maternal age (P = 0.032; 95% CI, 0.819-0.991) were the risk factors for ROP
      development and GA (P < 0.001; 95% CI, 0.387-0.609) and lower maternal age (P =
      0.012; 95% CI, 0.795-0.973) were for laser treatment. The odds ratio of requiring
      laser treatment was 3.3 when the maternal age was <33 years. Conclusion. ROP was
      more likely to be developed and progressed in infants born from younger mother
      and low GA. 

PMID- 24876946
TI  - Response time, visual search strategy, and anticipatory skills in volleyball
      players.
AB  - This paper aimed at comparing expert and novice volleyball players in a
      visuomotor task using realistic stimuli. Videos of a volleyball setter performing
      offensive action were presented to participants, while their eye movements were
      recorded by a head-mounted video based eye tracker. Participants were asked to
      foresee the direction (forward or backward) of the setter's toss by pressing one
      of two keys. Key-press response time, response accuracy, and gaze behaviour were
      measured from the first frame showing the setter's hand-ball contact to the
      button pressed by the participants. Experts were faster and more accurate in
      predicting the direction of the setting than novices, showing accurate
      predictions when they used a search strategy involving fewer fixations of longer
      duration, as well as spending less time in fixating all display areas from which
      they extract critical information for the judgment. These results are consistent
      with the view that superior performance in experts is due to their ability to
      efficiently encode domain-specific information that is relevant to the task. 

PMID- 24876947
TI  - Salient distractors can induce saccade adaptation.
AB  - When saccadic eye movements consistently fail to land on their intended target,
      saccade accuracy is maintained by gradually adapting the movement size of
      successive saccades. The proposed error signal for saccade adaptation has been
      based on the distance between where the eye lands and the visual target (retinal
      error). We studied whether the error signal could alternatively be based on the
      distance between the predicted and actual locus of attention after the saccade.
      Unlike conventional adaptation experiments that surreptitiously displace the
      target once a saccade is initiated towards it, we instead attempted to draw
      attention away from the target by briefly presenting salient distractor images on
      one side of the target after the saccade. To test whether less salient, more
      predictable distractors would induce less adaptation, we separately used fixed
      random noise distractors. We found that both visual attention distractors were
      able to induce a small degree of downward saccade adaptation but significantly
      more to the more salient distractors. As in conventional adaptation experiments,
      upward adaptation was less effective and salient distractors did not
      significantly increase amplitudes. We conclude that the locus of attention after
      the saccade can act as an error signal for saccade adaptation. 

PMID- 24876948
TI  - The difference in translaminar pressure gradient and neuroretinal rim area in
      glaucoma and healthy subjects.
AB  - Purpose. To assess differences in translaminar pressure gradient (TPG) and
      neuroretinal rim area (NRA) in patients with normal tension glaucoma (NTG), high
      tension glaucoma (HTG), and healthy controls. Methods. 27 patients with NTG, HTG,
      and healthy controls were included in the prospective pilot study (each group
      consisted of 9 patients). Intraocular pressure (IOP), intracranial pressure
      (ICP), and confocal laser scanning tomography were assessed. TPG was calculated
      as the difference of IOP minus ICP. ICP was measured using noninvasive two-depth
      transcranial Doppler device. The level of significance P < 0.05 was considered
      significant. Results. NTG patients had significantly lower IOP (13.7(1.6) mmHg),
      NRA (0.97(0.36) mm(2)), comparing with HTG and healthy subjects, P < 0.05. ICP
      was lower in NTG (7.4(2.7) mmHg), compared with HTG (8.9(1.9) mmHg) and healthy
      subjects (10.5(3.0) mmHg); however, the difference between groups was not
      statistically significant (P > 0.05). The difference between TPG for healthy
      (5.4(7.7) mmHg) and glaucomatous eyes (NTG 6.3(3.1) mmHg, HTG 15.7(7.7) mmHg) was
      statistically significant (P < 0.001). Higher TPG was correlated with decreased
      NRA (r = -0.83; P = 0.01) in the NTG group. Conclusion. Translaminar pressure
      gradient was higher in glaucoma patients. Reduction of NRA was related to higher
      TPG in NTG patients. Further prospective studies are warranted to investigate the
      involvement of TPG in glaucoma management. 

PMID- 24876949
TI  - Elements of the B cell signalosome are differentially affected by mercury
      intoxication.
AB  - It has been suggested that environmental exposures to mercury contribute to
      autoimmune disease. Disruption of BCR signaling is associated with failure of
      central tolerance and autoimmunity, and we have previously shown that low levels
      of Hg(2+) interfere with BCR signaling. In this report we have employed
      multiparametric phosphoflow cytometry, as well as a novel generalization of the
      Overton algorithm from one- to two-dimensional unimodal distributions to
      simultaneously monitor the effect of low level Hg(2+) intoxication on activation
      of ERK and several upstream elements of the BCR signaling pathway in WEHI-231 B
      cells. We have found that, after exposure to low levels of Hg(2+), only about a
      third of the cells are sensitive to the metal. For those cells which are
      sensitive, we confirm our earlier work that activation of ERK is attenuated but
      now report that Hg(2+) has little upstream effect on the Btk tyrosine kinase. On
      the other hand, we find that signaling upstream through the Syk tyrosine kinase
      is actually augmented, as is upstream activation of the B cell signalosome
      scaffolding protein BLNK. 

PMID- 24876952
TI  - The challenges of conducting a nurse-led intervention in a randomized controlled
      trial with vulnerable participants.
AB  - This paper discusses the challenges encountered by researchers while conducting a
      randomized controlled trial (RCT) testing the efficacy of a healthy lifestyle
      educational and exercise intervention for people with serious mental illness.
      RCTs, even though considered the "gold standard" of research designs, are still
      prone to risks of potential bias and threats to their validity. Based on
      researcher reflexivity, the combination of reflection and action, during the
      conduct of the study, this paper outlines a number of challenges faced by the
      researchers. These included managing the need of participants to tell their story
      and be heard, reluctance of participants to remain in allocated groups,
      participant literacy, dual role of the nurse nurse-researcher, and reporting the
      benefits of nonstatistical results of a quantitative research project.
      Recommendations for conducting future behaviour intervention studies of this type
      include the incorporation of a reflexive component for the nurse nurse
      researcher, highlighting the importance of taking a reflexive stance in both
      qualitative and quantitative research designs. 

PMID- 24876950
TI  - Potential Sources and Roles of Adaptive Immunity in Age-Related Macular
      Degeneration: Shall We Rename AMD into Autoimmune Macular Disease?
AB  - Age-related macular degeneration (AMD) is the leading cause of vision loss in the
      elderly throughout the industrialized world. Its most prominent pathologic
      features are lesions involving the retinal pigment epithelium (RPE) the Bruch's
      membrane, the degeneration of photoreceptors, and, in the most aggressive cases,
      choroidal neovascularization. Genetic associations between the risk of developing
      AMD and polymorphism within components of the complement system, as well as
      chemokine receptors expressed on microglial cells and macrophages, have linked
      retinal degeneration and choroidal neovascularization to innate immunity
      (inflammation). In addition to inflammation, players of the adaptive immunity
      including cytokines, chemokines, antibodies, and T cells have been detected in
      animal models of AMD and in patients suffering from this pathology. These
      observations suggest that adaptive immunity might play a role in different
      processes associated with AMD such as RPE atrophy, neovascularization, and
      retinal degeneration. To this date however, the exact roles (if any) of
      autoantibodies and T cells in AMD remain unknown. In this review we discuss the
      potential effects of adaptive immune responses in AMD pathogenesis. 

PMID- 24876951
TI  - Autoimmunity and asbestos exposure.
AB  - Despite a body of evidence supporting an association between asbestos exposure
      and autoantibodies indicative of systemic autoimmunity, such as antinuclear
      antibodies (ANA), a strong epidemiological link has never been made to specific
      autoimmune diseases. This is in contrast with another silicate dust, crystalline
      silica, for which there is considerable evidence linking exposure to diseases
      such as systemic lupus erythematosus, systemic sclerosis, and rheumatoid
      arthritis. Instead, the asbestos literature is heavily focused on cancer,
      including mesothelioma and pulmonary carcinoma. Possible contributing factors to
      the absence of a stronger epidemiological association between asbestos and
      autoimmune disease include (a) a lack of statistical power due to relatively
      small or diffuse exposure cohorts, (b) exposure misclassification, (c) latency of
      clinical disease, (d) mild or subclinical entities that remain undetected or
      masked by other pathologies, or (e) effects that are specific to certain fiber
      types, so that analyses on mixed exposures do not reach statistical significance.
      This review summarizes epidemiological, animal model, and in vitro data related
      to asbestos exposures and autoimmunity. These combined data help build toward a
      better understanding of the fiber-associated factors contributing to immune
      dysfunction that may raise the risk of autoimmunity and the possible contribution
      to asbestos-related pulmonary disease. 

PMID- 24876953
TI  - Physician Orders for Life Sustaining Treatment in US Nursing Homes: A Case Study
      of CRNP Engagement in the Care Planning Process.
AB  - This case study describes changes in Physician Orders for Life Saving Treatment
      (POLST) status among long-stay residents of a US nursing home who had a certified
      registered nurse practitioner (CRNP) adopt the practice of participating in
      nursing home staff care plan meetings. The CRNP attended a nonrandomized sample
      of 60 care plan meetings, each featuring a review of POLST preferences with
      residents and/or family members. Days since original POLST completion, Charlson
      Comorbidity Index score, number of hospitalizations since index admission, and
      other sociodemographic characteristics including religion and payer source were
      among the data elements extracted via chart review for the sample as well as for
      a nonequivalent control group of 115 residents also under the care of the medical
      provider group practice at the nursing home. Twenty-three percent (n = 14) of the
      60 care conferences attended by the CRNP resulted in a change in POLST status
      after consultations with the resident and/or family. In all cases, POLST changes
      involved restated preferences from a higher level of intervention to a lower
      level of intervention. Fifty-nine percent of the CRNP-attended conferences
      resulted in the issuance of new medical provider orders. CRNP participation in
      care conferences may represent a best practice opportunity to revisit goals of
      care with individuals and their family members in the context of broader
      interprofessional treatment planning. 

PMID- 24876954
TI  - Validating SPICES as a Screening Tool for Frailty Risks among Hospitalized Older
      Adults.
AB  - Older patients are vulnerable to adverse hospital events related to frailty.
      SPICES, a common screening protocol to identify risk factors in older patients,
      alerts nurses to initiate care plans to reduce the probability of patient harm.
      However, there is little published validating the association between SPICES and
      measures of frailty and adverse outcomes. This paper used data from a prospective
      cohort study on frailty among 174 older adult inpatients to validate SPICES.
      Almost all patients met one or more SPICES criteria. The sum of SPICES was
      significantly correlated with age and other well-validated assessments for
      vulnerability, comorbid conditions, and depression. Individuals meeting two or
      more SPICES criteria had a risk of adverse hospital events three times greater
      than individuals with either no or one criterion. Results suggest that as a
      screening tool used within 24 hours of admission, SPICES is both valid and
      predictive of adverse events. 

PMID- 24876955
TI  - Prospective Observational Study of Single-Site Multiport Per-umbilical
      Laparoscopic Endosurgery versus Conventional Multiport Laparoscopic
      Cholecystectomy: Critical Appraisal of a Unique Umbilical Approach.
AB  - Purpose. This prospective observational study compares an innovative approach of
      Single-Site Multi-Port Per-umbilical Laparoscopic Endo-surgery (SSMPPLE)
      cholecystectomy with the gold standard-Conventional Multi-port Laparoscopic
      Cholecystectomy (CMLC)-to assess the feasibility and efficacy of the former.
      Methods. In all, 646 patients were studied. SSMPPLE cholecystectomy utilized
      three ports inserted through three independent mini-incisions at the umbilicus.
      Only the day-to-day rigid laparoscopic instruments were used in all cases. The
      SSMPPLE cholecystectomy group had 320 patients and the CMLC group had 326
      patients. The outcomes were statistically compared. Results. SSMPPLE
      cholecystectomy had average operative time of 43.8 min and blood loss of 9.4 mL.
      Their duration of hospitalization was 1.3 days (range, 1-5). Six patients (1.9%)
      of this group were converted to CMLC. Eleven patients had controlled gallbladder
      perforations at dissection. The Visual Analogue Scores for pain on postoperative
      days 0 and 7, the operative time, and the scar grades were significantly better
      for SSMPPLE than CMLC. However, umbilical sepsis and seroma outcomes were
      similar. We had no bile-duct injuries or port-site hernias in this study.
      Conclusion. SSMPPLE cholecystectomy approach complies with the principles of
      laparoscopic triangulation; it seems feasible and safe method of minimally
      invasive cholecystectomy. Overall, it has a potential to emerge as an
      economically viable alternative to single-port surgery. 

PMID- 24876957
TI  - Effect of pregabalin and dexamethasone on postoperative analgesia after
      septoplasty.
AB  - Objectives. The aim of this study was to explore effect of a combination of
      pregabalin and dexamethasone on pain control after septoplasty operations.
      Methods. In this study, 90 patients who were scheduled for septoplasty under
      general anesthesia were randomly assigned into groups that received either
      placebo (Group C), pregabalin (Group P), or pregabalin and dexamethasone (Group
      PD). Preoperatively, patients received either pregabalin 300 mg one hour before
      surgery, dexamethasone 8 mg intravenously during induction, or placebo according
      to their allocation. Postoperative pain treatment included tramadol and
      diclofenac sodium 30 minutes before the end of the operation. Numeric rating
      scale (NRS) for pain assessment, side effects, and consumption of tramadol,
      pethidine, and ondansetron were recorded. Results. The median NRS score at the
      postoperative 0 and the 2nd h was significantly higher in Group C than in Group P
      and Group PD (P <= 0.004 for both). The 24 h tramadol and pethidine, consumptions
      were significantly reduced in Groups P and PD compared to Group C (P < 0.001 and
      P < 0.001). The incidence of blurred vision was significantly higher in Group PD
      compared to Group C within both 0-2 h and 0-24 h periods (P = 0.002 and P <
      0.001, resp.). Conclusions. We conclude that administration of 300 mg pregabalin
      preoperatively may be an adequate choice for pain control after septoplasty.
      Addition of dexamethasone does not significantly reduce pain in these patients. 

PMID- 24876958
TI  - Frequency and intensive care related risk factors of pneumothorax in ventilated
      neonates.
AB  - OBJECTIVES: Relationships of mechanical ventilation to pneumothorax in neonates
      and care procedures in particular are rarely studied. We aimed to evaluate the
      relationship of selected ventilator variables and risk events to pneumothorax.
      METHODS: Pneumothorax was defined as accumulation of air in pleural cavity as
      confirmed by chest radiograph. Relationship of ventilator mode, selected
      settings, and risk procedures prior to detection of pneumothorax was studied
      using matched controls. RESULTS: Of 540 neonates receiving mechanical
      ventilation, 10 (1.85%) were found to have pneumothorax. Respiratory distress
      syndrome, meconium aspiration syndrome, and pneumonia were the underlying lung
      pathology. Pneumothorax mostly (80%) occurred within 48 hours of life. Among
      ventilated neonates, significantly higher percentage with pneumothorax received
      mandatory ventilation than controls (70% versus 20%; P < 0.01). Peak inspiratory
      pressure >20 cm H2O and overventilation were not significantly associated with
      pneumothorax. More cases than controls underwent care procedures in the preceding
      3 hours of pneumothorax event. Mean airway pressure change (P = 0.052) and
      endotracheal suctioning (P = 0.05) were not significantly associated with
      pneumothorax. Reintubation (P = 0.003), and bagging (P = 0.015) were
      significantly associated with pneumothorax. CONCLUSION: Pneumothorax among
      ventilated neonates occurred at low frequency. Mandatory ventilation and selected
      care procedures in the preceding 3 hours had significant association.

PMID- 24876956
TI  - Barriers and delays in tuberculosis diagnosis and treatment services: does gender
      matter?
AB  - Background. Tuberculosis (TB) remains a global public health problem with known
      gender-related disparities. We reviewed the quantitative evidence for gender
      related differences in accessing TB services from symptom onset to treatment
      initiation. Methods. Following a systematic review process, we: searched 12
      electronic databases; included quantitative studies assessing gender differences
      in accessing TB diagnostic and treatment services; abstracted data; and assessed
      study validity. We defined barriers and delays at the individual and
      provider/system levels using a conceptual framework of the TB care continuum and
      examined gender-related differences. Results. Among 13,448 articles, 137 were
      included: many assessed individual-level barriers (52%) and delays (42%), 76%
      surveyed persons presenting for care with diagnosed or suspected TB, 24% surveyed
      community members, and two-thirds were from African and Asian regions. Many
      studies reported no gender differences. Among studies reporting disparities,
      women faced greater barriers (financial: 64% versus 36%; physical: 100% versus
      0%; stigma: 85% versus 15%; health literacy: 67% versus 33%; and provider-/system
      level: 100% versus 0%) and longer delays (presentation to diagnosis: 45% versus
      0%) than men. Conclusions. Many studies found no quantitative gender-related
      differences in barriers and delays limiting access to TB services. When
      differences were identified, women experienced greater barriers and longer delays
      than men. 

PMID- 24876959
TI  - Quality of Sleep in an HIV Population on Antiretroviral Therapy at an Urban
      Tertiary Centre in Lagos, Nigeria.
AB  - Aim. To determine the prevalence of sleep disturbance and its associated
      characteristics in HIV-positive outpatients on HAART using the PSQI. Methods.
      Using a cross-sectional design, 300 patients attending the outpatient HIV/AIDS
      clinic at the Lagos State University Teaching Hospital were recruited. Baseline
      data obtained included the participants' demographic data, educational
      qualification, and marital status. Their treatment history, including duration
      since HIV diagnosis, the most recent CD4 cell count, and current antiretroviral
      therapies, was obtained from their case records. Each participant completed the
      PSQI questionnaire and those with scores >=5 were diagnosed with poor sleep
      quality. Results. The participants were made up of 70.7% females and 29.3% males.
      Their ages ranged between 18 and 74 years with a mean of 38.9 +/- 10.3 years.
      According to the PSQI, 59.3% reported poor sleep quality. The mean score of those
      with poor quality sleep (9.2 +/- 3.3) was comparable to that of those with good
      quality sleep (1.26 +/- 1.4). P < 0.001. Significant differences were observed in
      all the individual components of the PSQI (P < 0.001). On multivariate analyses,
      the independent associations with sleep quality were the duration since HIV
      diagnosis (P = 0.29), efavirenz based regimen (P < 0.001), and lower CD4 cell
      count (P < 0.001). Conclusions. Sleep disturbances are quite common in the HIV
      population even in the era of HAART. Early recognition via routine assessment and
      effective treatments could prevent the resultant complications and improve
      quality of life. 

PMID- 24876961
TI  - Characteristics of children who lost the diagnosis of autism: a sample from
      istanbul, Turkey.
AB  - Aim. The aim of this study was to describe a group of children who lost a
      diagnosis of autism following participation in early educational programs.
      Method. This is a descriptive study reporting the characteristics of children (n:
      39) who lost their diagnosis of autism and explaining the educational programs
      that these children followed. The data were collected by reviewing the
      participants' files and through examinations. Results. All of the children were
      placed at regular psychiatric follow-ups. The mean age at referral was 2.39+/
      0.75 years, whereas the mean age at the time of optimal outcome reported was 5.11
      +/- 1.95 years. Two of the children were in early intensive behavioral
      intervention (EIBI), and the rest were in a comprehensive naturalistic behavioral
      program. The childhood autism rating scale (CARS) total scores at baseline and
      final were 32.75 +/- 3.15 and 18.01 +/- 1.76, respectively. The mean IQ of the
      group at final examination was 116.70 +/- 18.88. Conclusion. It could be
      concluded that a group of children with an autism diagnosis could lose the
      diagnosis of autism upon early intervention. High IQ and the development of
      communicative and language skills at an early age could be the most powerful
      factors contributing to an optimal outcome. 

PMID- 24876960
TI  - Peripheral cytokines as a chemical mediator for postconcussion like sickness
      behaviour in trauma and perioperative patients: literature review.
AB  - Besides brain injury and systemic infection, cognitive and concussion like
      sickness behaviour is associated with muscular trauma and perioperative patients,
      which represents a major obstacle to daily activities and rehabilitation. The
      neuroinflammatory response triggers glial activation and consequently the release
      of proinflammatory cytokines within the hippocampus. We review clinical studies
      that have investigated neurocognitive and psychosomatic symptoms related to
      muscular trauma and in perioperative conditions. These include impaired attention
      and executive and general cognitive functioning. The purpose of this literature
      review is to focus on the systemic inflammation and the role of proinflammatory
      cytokines IL1, IL6,and TNF and other inflammatory mediators which mediates the
      cognitive impairment and induces sickness behaviour. Moreover, this review will
      also help to determine if some patients could have long-term cognitive changes
      associated with musculoskeletal injuries or as a consequence of surgery and
      thereby will lead to efforts in reducing that risk. 

PMID- 24876962
TI  - Long-term risperidone treatment induces visceral adiposity associated with
      hepatic steatosis in mice: a magnetic resonance approach.
AB  - Although atypical antipsychotic drugs (APDs) have led to significant advances in
      the treatment of psychotic disorders, they still induce metabolic disturbances.
      We aimed at characterizing the metabolic consequences of a risperidone treatment
      and at establishing a link with noninvasive MR markers, in order to develop a
      tool for predicting symptoms of the metabolic syndrome. Fat deposition and liver
      morphometry were assessed by T1-weighted imaging. Fatty acid composition and fat
      accumulations in tissues were determined using MR spectroscopy with and without
      water suppression, respectively. Risperidone treatment induced a weight gain
      accompanied with metabolic disturbances such as hyperglycemic status, an increase
      in visceral adipose tissue (VAT), and liver fat depositions. Correlations using
      Methylene-Water Ratio (MWR) and Polyunsaturated Index (PUI) demonstrated a
      concomitant increase in the weight gain, VAT and liver fat depositions, and a
      decrease in the quantity of polyunsaturated fatty acids. These results were
      consistent with a hepatic steatosis state. We evaluated the ability of MR
      techniques to detect subtle metabolic disorders induced by APDs. Thus, our model
      and methodology offer the possibility to investigate APDs side effects in order
      to improve the health conditions of schizophrenic patients. 

PMID- 24876963
TI  - Ferric carboxymaltose-mediated attenuation of Doxorubicin-induced cardiotoxicity
      in an iron deficiency rat model.
AB  - Since anthracycline-induced cardiotoxicity (AIC), a complication of anthracycline
      based chemotherapies, is thought to involve iron, concerns exist about using iron
      for anaemia treatment in anthracycline-receiving cancer patients. This study
      evaluated how intravenous ferric carboxymaltose (FCM) modulates the influence of
      iron deficiency anaemia (IDA) and doxorubicin (3-5 mg per kg body weight [BW]) on
      oxidative/nitrosative stress, inflammation, and cardiorenal function in
      spontaneously hypertensive stroke-prone (SHR-SP) rats. FCM was given as repeated
      small or single total dose (15 mg iron per kg BW), either concurrent with or
      three days after doxorubicin. IDA (after dietary iron restriction) induced
      cardiac and renal oxidative stress (markers included malondialdehyde, catalase,
      Cu,Zn-superoxide dismutase, and glutathione peroxidase), nitrosative stress
      (inducible nitric oxide synthase and nitrotyrosine), inflammation (tumour
      necrosis factor-alpha and interleukin-6), and functional/morphological
      abnormalities (left ventricle end-diastolic and end-systolic diameter, fractional
      shortening, density of cardiomyocytes and capillaries, caveolin-1 expression,
      creatinine clearance, and urine neutrophil gelatinase-associated lipocalin) that
      were aggravated by doxorubicin. Notably, iron treatment with FCM did not
      exacerbate but attenuated the cardiorenal effects of IDA and doxorubicin
      independent of the iron dosing regimen. The results of this model suggest that
      intravenous FCM can be used concomitantly with an anthracycline-based
      chemotherapy without increasing signs of AIC. 

PMID- 24876964
TI  - Estimated visceral adipose tissue, but not body mass index, is associated with
      reductions in glomerular filtration rate based on cystatin C in the early stages
      of chronic kidney disease.
AB  - Information on the association between obesity and initial phases of chronic
      kidney disease (CKD) is still limited, principally those regarding the influence
      of visceral adipose tissue. We investigated whether the visceral adipose tissue
      is more associated with reductions in glomerular filtration rate (GFR) than total
      and abdominal obesity in hypertensive individuals with stage 1-2 CKD. A cross
      sectional study was implemented which involved 241 hypertensive patients
      undergoing treatment at a primary health care facility. GFR was estimated using
      equations based on creatinine and cystatin C levels. Explanatory variables
      included body mass index (BMI), waist circumference (WC), and estimated visceral
      adipose tissue (eVAT). The mean age was 59.6 +/- 9.2 years old and 75.9% were
      female. According to BMI, 28.2% of subjects were obese. Prevalence of increased
      WC and eVAT was 63.9% and 58.5%, respectively. Results from the assessment of GFR
      by BMI, WC, and eVAT categories showed that only women with increased eVAT (>=150
      cm(2)) had a lower mean GFR by Larsson (P = 0.016), Levey 2 (P = 0.005), and
      Levey 3 (P = 0.008) equations. The same result was not observed when the MDRD
      equation was employed. No association was found between BMI, WC, eVAT, and GFR
      using only serum creatinine. In the early stages of CKD, increased eVAT in
      hypertensive women was associated with decreased GFR based on cystatin C. 

PMID- 24876965
TI  - Expression of TPM1kappa, a Novel Sarcomeric Isoform of the TPM1 Gene, in Mouse
      Heart and Skeletal Muscle.
AB  - We have investigated the expression of TPM1 alpha and TPM1 kappa in mouse
      striated muscles. TPM1 alpha and TMP1 kappa were amplified from the cDNA of mouse
      heart by using conventional RT-PCR. We have cloned the PCR amplified DNA and
      determined the nucleotide sequences. Deduced amino acid sequences show that there
      are three amino acid changes in mouse exon 2a when compared with the human TPM1
      kappa . However, the deduced amino acid sequences of human TPM1 alpha and mouse
      TPM1 alpha are identical. Conventional RT-PCR data as well as qRT-PCR data,
      calculating both absolute copy number and relative expression, revealed that the
      expression of TPM1 kappa is significantly lower compared to TPM1 alpha in both
      mouse heart and skeletal muscle. It was also found that the expression level of
      TPM1 kappa transcripts in mouse heart is higher than it is in skeletal muscle. To
      the best of our knowledge, this is the first report of the expression of TPM1
      kappa in mammalian skeletal muscle. 

PMID- 24876966
TI  - Bedside tested ocular motor disorders in multiple sclerosis patients.
AB  - Background/Aims. Ocular motor disorders (OMDs) are a common feature of multiple
      sclerosis (MS). In clinical practice, if not reported by patients, OMDs are often
      underdiagnosed and their prevalence is underestimated. Methods. We studied 163
      patients (125 women, 76.7%, 38 men, 23.3%; median age 45.0 years; median disease
      duration 10 years; median EDSS 3.5) with definite MS (n = 150, 92%) or clinically
      isolated syndrome (n = 13, 8%) who underwent a thorough clinical examination of
      eye movements. Data on localization of previous relapses, MS subtype, and MRI
      findings were collected and analyzed. Results. Overall, 111/163 (68.1%) patients
      showed at least one abnormality of eye movement. Most frequent OMDs were impaired
      smooth pursuit (42.3%), saccadic dysmetria (41.7%), unilateral internuclear
      ophthalmoplegia (14.7%), slowing of saccades (14.7%), skew deviation (13.5%), and
      gaze evoked nystagmus (13.5%). Patients with OMDs had more severe disability (P =
      0.0005) and showed more frequently infratentorial MRI lesions (P = 0.004).
      Localization of previous relapses was not associated with presence of OMDs.
      Conclusion. OMDs are frequent in patients with stable (no relapses) MS. A precise
      bedside examination of eye motility can disclose abnormalities that imply the
      presence of subclinical MS lesions and may have a substantial impact on
      definition of the diagnosis and on management of MS patients. 

PMID- 24876967
TI  - Morphogenesis of Mammary Glands in Buffalo (Bubalus bubalis).
AB  - The present research was elucidated on the morphogenesis of mammary gland of
      buffalo during prenatal development. Total of 16 foetuses ranging from 1.2 cm (34
      days) to 108 cm CVRL (curved crown rump length) (317 days) were used for study.
      The study revealed that mammary line was first observed at 1.2 cm CVRL (34 days),
      mammary hillock at 1.7 cm (37 days), and mammary bud at 2.6 cm CVRL (41 days)
      foetuses. Epidermal cone was found at 6.7 cm CVRL (58 days) whereas primary and
      secondary ducts were observed at 7.4 cm CVRL (62 days) and 15 cm CVRL (96 days),
      respectively. Connective tissue whorls were reported at 18.2 cm CVRL (110 days)
      and internal elastic lamina and muscle layers at 24.1 cm CVRL (129 days). Lobules
      were observed at 29.3 cm CVRL (140 days), rosette of furstenberg at 39.5 cm CVRL
      (163 days), and keratin plug at 45.5 cm CVRL (176 days) foetus. Primordia of
      sweat and sebaceous glands around hair follicle were seen at 21.2 cm CVRL (122
      days) of foetal life. Differentiation of all the skin layers along with
      cornification was observed at 69 cm (229 days) in group III foetuses. 

PMID- 24876968
TI  - The efficacy of nebulized furosemide and salbutamol compared with salbutamol
      alone in reactive airway disease: a double blind randomized, clinical trial.
AB  - We undertook this randomized clinical trial to investigate whether adding
      furosemide to salbutamol could improve the peak expiratory flow rate (PEFR) and
      clinical signs of reactive airway disease (RAD) patients. Eligible 18- to 55-year
      old patients were randomly divided into intervention and control groups. Patients
      received 5 mg of nebulized salbutamol and 40 mg of nebulized furosemide in the
      intervention group and 5 mg of nebulized salbutamol alone in the control group.
      Patients in both groups received 100 mg of methylprednisolone intravenously stat.
      Severity of the RAD was estimated before and 45 minutes after treatment in both
      groups. PEFR was estimated before treatment and at 15, 30, and 45 minutes later.
      Ninety patients were enrolled, 45 in each group. There were no significant
      differences between two groups regarding gender, mean age, and normalized PEFR.
      The baseline mean PEFR was not significantly different between groups (P = 0.58).
      A repeated measure analysis of variance revealed that the differences between the
      two treatments was significant (P = 0.0001) and the behavior of two treatments
      was not similar across the time (P = 0.001). Comparison of clinical severity of
      acute RAD revealed no significant differences between groups at the end of the
      trial (0.06). This study showed that adding nebulized furosemide to salbutamol in
      RAD patients improved PEFR. 

PMID- 24876970
TI  - Autologous Graft versus Host Disease: An Emerging Complication in Patients with
      Multiple Myeloma.
AB  - Autologous graft versus host disease (autoGVHD) is a rare transplant complication
      with significant morbidity and mortality. It has been hypothesized that patients
      with multiple myeloma might be predisposed to autoGVHD through dysregulation of
      the immune response resulting from either their disease, the immunomodulatory
      agents (IMiDs) used to treat it, or transplant conditioning regimen.
      Hematopoietic progenitor cell (HPC) products were available from 8 multiple
      myeloma patients with biopsy-proven autoGVHD, 16 matched multiple myeloma
      patients who did not develop autoGVHD, and 7 healthy research donors. The data on
      number of transplants prior to developing autoGVHD, mobilization regimens,
      exposure to proteasome inhibitors, use of IMiDs, and class I human leukocyte
      antigen types (HLA A and B) were collected. The HPC products were analyzed by
      flow cytometry for expression of CD3, CD4, CD8, CD25, CD56, and FoxP3. CD3(+)
      cell number was significantly lower in autoGVHD patients compared to unaffected
      controls (P = 0.047). On subset analysis of CD3(+) cells, CD8(+) cells (but not
      CD4(+) cells) were found to be significantly lower in patients with autoGVHD (P =
      0.038). HLA-B55 expression was significantly associated with development of
      autoGVHD (P = 0.032). Lower percentages of CD3(+) and CD8(+) T-cells and HLA-B55
      expression may be predisposing factors for developing autoGVHD in myeloma. 

PMID- 24876969
TI  - Assessing function and endurance in adults with spinal and bulbar muscular
      atrophy: validity of the adult myopathy assessment tool.
AB  - Purpose. The adult myopathy assessment tool (AMAT) is a performance-based battery
      comprised of functional and endurance subscales that can be completed in
      approximately 30 minutes without the use of specialized equipment. The purpose of
      this study was to determine the construct validity and internal consistency of
      the AMAT with a sample of adults with spinal and bulbar muscular atrophy (SBMA).
      Methods. AMAT validity was assessed in 56-male participants with genetically
      confirmed SBMA (mean age, 53 +/- 10 years). The participants completed the AMAT
      and assessments for disease status, strength, and functional status. Results.
      Lower AMAT scores were associated with longer disease duration (r = -0.29; P <
      0.03) and lower serum androgen levels (r = 0.49-0.59; P < 0.001). The AMAT was
      significantly correlated with strength and functional status (r = 0.82-0.88; P <
      0.001). The domains of the AMAT exhibited good internal consistency (Cronbach's
      alpha  = 0.77-0.89; P < 0.001). Conclusions. The AMAT is a standardized,
      performance-based tool that may be used to assess functional limitations and
      muscle endurance. The AMAT has good internal consistency, and the construct
      validity of the AMAT is supported by its significant associations with hormonal,
      strength, and functional characteristics of adults with SBMA. This trial is
      registered with Clinicaltrials.gov identifier NCT00303446. 

PMID- 24876972
TI  - Radiographic markers of femoroacetabular impingement: correlation of herniation
      pit and femoral bump with a positive cross-over ratio.
AB  - Introduction. The goal of this study was to research the association of femoral
      bumps and herniation pits with the overlap-ratio of the cross-over sign. Methods.
      Pelvic X-rays and CT-scans of 2925 patients with good assessment of the anterior
      and the posterior acetabular wall and absence of neutral pelvic tilt were
      enrolled in the investigation. Finally pelvic X-rays were assessed for the
      presence of a positive cross-over sign, and CT-scans for a femoral bump or a
      herniation pit. Additionally, if a positive cross-over sign was discovered, the
      overlap-ratio was calculated. Results. A femoral bump was found in 53.3% (n =
      1559), and a herniation pit in 27.2% (n = 796) of all hips. The overlap-ratio
      correlated positively with the presence of a femoral bump, while a negative
      correlation between the overlap-ratio and the presence of a herniation pit was
      found. The latter was significantly more often combined with a femoral bump than
      without. Conclusions. We detected an increased prevalence of femoral bump with
      increasing overlap-ratios of the cross-over sign indicating a relation to
      biomechanical stress. The observed decreased prevalence of herniation pits with
      increasing overlap-ratios could be explained by reduced mechanical stress due to
      nontightened iliofemoral ligament in the presence of retroversion of the
      acetabulum. 

PMID- 24876973
TI  - Sleep and emotional and behavioral symptoms in adolescents with inflammatory
      bowel disease.
AB  - The current study assessed the associations between sleep and psychosocial
      symptoms in 157 Finnish adolescents with inflammatory bowel disease (IBD). Sleep
      trouble was self-rated in Sleep Self-Report (SSR) and in Youth Self-Report (YSR).
      Psychosocial symptoms of the adolescents were assessed by the YSR and Child
      Behavior Checklist (CBCL). Patients reporting sleep trouble had significantly
      more psychosocial symptoms than their counterparts without sleep trouble. This
      was shown in the CBCL and YSR scales of total problems (P < 0.01),
      anxious/depressed mood (P < 0.05), and aggressive behavior (P < 0.01).
      Additionally, SSR sleep problem subscale scores indicating lower sleep quality
      (bedtime, sleep behavior) associated significantly with attention problems (P <
      0.05). These results point out that sleep trouble should be recognized and
      treated in adolescents with IBD to possibly avoid the emerging of psychosocial
      symptoms. 

PMID- 24876974
TI  - The Effect of the Transition to Home Monitoring for the Diagnosis of OSAS on Test
      Availability, Waiting Time, Patients' Satisfaction, and Outcome in a Large Health
      Provider System.
AB  - During 2009, the Haifa district of Clalit Health Services (CHS) has switched from
      in-lab polysomnography (PSG) to home studies for the diagnosis of obstructive
      sleep apnea (OSA). We assessed the effects of this change on accessibility,
      waiting time, satisfaction, costs, and CPAP purchase by the patients. Data
      regarding sleep studies, CPAP purchase, and waiting times were collected
      retrospectively from the computerized database of CHS. Patients' satisfaction was
      assessed utilizing a telephone questionnaire introduced to a randomized small
      sample of 70 patients. Comparisons were made between 2007 and 2008 (in-lab PSGs)
      and 2010 and 2011 (when most studies were ambulatory). Of about 650000 insured
      individuals in the Haifa district of CHS, 1471 sleep studies were performed
      during 2007-2008 compared to 2794 tests during 2010-2011. The average waiting
      time was 9.9 weeks in 2007-2008 compared to 1.1 weeks in 2010-2011 (P < 0.05).
      597 CPAPs were purchased in 2007-2008 compared to 831 in 2010-2011. The overall
      patients' satisfaction was similar, but discomfort tended to be higher in the in
      laboratory group (4.1 vs 2.7 in a scale of 0-10; P = 0.11). Switching to
      ambulatory diagnosis improved the test accessibility and reduced the waiting
      times. Patients' satisfaction remained similarly high. The total direct cost of
      OSA management was reduced. 

PMID- 24876975
TI  - Validation of the CPAP Habit Index-5: A Tool to Understand Adherence to CPAP
      Treatment in Patients with Obstructive Sleep Apnea.
AB  - Long-term adherence to continuous positive airway pressure (CPAP) is low among
      patients with obstructive sleep apnea (OSA). The potential role of "habit" in
      sustaining adherence to CPAP use has not been studied. This study aimed to
      establish the relevance of habit to CPAP adherence, via validation of an
      adaptation of the Self-Report Habit Index (the CPAP Habit Index-5; CHI-5).
      Analyses focused on the homogeneity, reliability, and factor structure of the CHI
      5 and, in line with theoretical predictions, its utility as a predictor of long
      term CPAP adherence in middle-aged patients with OSA. A prospective longitudinal
      design was used. 117 patients with objectively verified OSA intended for CPAP
      treatment were recruited. Data was collected via clinical examinations,
      respiratory recordings, questionnaires, and CPAP devices at baseline, 2 weeks, 6
      months, and 12 months. The CHI-5 showed satisfactory homogeneity interitem
      correlations (0.42-0.93), item-total correlations (0.58-0.91), and reliability (
      alpha = 0.92). CHI-5 data at 6 months showed a one-factor solution and predicted
      63% of variance in total CPAP use hours after 12 months. Based on the
      satisfactory measurement properties and the high amount of CPAP use variance it
      explained, the CHI-5 can be seen as a useful tool in clinical practice. 

PMID- 24876976
TI  - Spontaneous recovery of paraplegia caused by spinal epidural hematoma after
      removal of epidural catheter.
AB  - We report a patient who developed paraplegia caused by a spinal epidural hematoma
      after removal of an epidural catheter, which resolved spontaneously. A 60-year
      old woman underwent thoracoscopic partial resection of the left lung under
      general anesthesia combined with epidural anesthesia. She neither was
      coagulopathic nor had received anticoagulants. Paraplegia occurred 40 minutes
      after removal of the epidural catheter on the first postoperative day. Magnetic
      resonance images revealed a spinal epidural hematoma. Surgery was not required as
      the paraplegia gradually improved until, within 1 hour, it had completely
      resolved. Hypoesthesia had completely resolved by the third postoperative day. 

PMID- 24876978
TI  - Necrotizing fasciitis of the nose complicated with cavernous sinus thrombosis.
AB  - Necrotizing fasciitis is a rapidly progressive life threatening bacterial
      infection of the skin, the subcutaneous tissue, and the fascia. We present a case
      of necrotizing fasciitis involving the nose complicated by cavernous sinus
      thrombosis. Few cases of septic cavernous sinus thrombosis have been reported to
      be caused by cellulitis of the face but necrotizing fasciitis of the nose is
      rare. It is very important to recognize the early signs of cavernous thrombosis.
      Treatment for septic cavernous sinus thrombosis is controversial but early use of
      empirical antibiotics is imperative. 

PMID- 24876977
TI  - Resolution of localized chronic periodontitis associated with longstanding
      calculus deposits.
AB  - This report, which is based on nonstandardized serial radiographs obtained over a
      period of 15 years, documents a case of localized chronic periodontitis
      associated with progressive deposition of calculus on the distal aspect of a
      mandibular second molar. The site was treated by scaling and root planing,
      followed by a course of adjunctive systemic azithromycin. Treatment yielded
      favorable reductions in probing depth and clinical inflammation, leaving only few
      isolated sites with pockets no deeper than 4 mm. Two years after completion of
      active treatment, there was radiographic evidence of increased bone density
      distal to the second molar. 

PMID- 24876979
TI  - Adenosquamous carcinoma of vesicovaginal fistula: a rare entity.
AB  - A 56-year-old lady presented with a vesicovaginal fistula (VVF) along with past
      history of abdominal hysterectomy. Biopsy of the fistulous tract showed squamous
      cell carcinoma (SCC). Patient underwent radical cystourethrectomy, total
      vaginectomy, and bilateral pelvic lymph node dissection along with ileal conduit.
      The final histopathology report of the resected specimen showed adenosquamous
      carcinoma in VVF. As this is a rare entity, we are reporting this case. 

PMID- 24876980
TI  - Rapidly progressed primary intestinal follicular lymphoma with elevation of
      soluble interleukin-2 receptor levels.
AB  - A 62-year-old Japanese male was diagnosed with primary intestinal follicular
      lymphoma involving the duodenum, jejunum, and rectum without lymph node
      involvement. The patient was classified as low risk by the follicular lymphoma
      international prognostic index (FLIPI) system. Treatment was deferred because he
      had no symptoms. Eleven months after the diagnosis, his soluble interleukin-2
      receptor (sIL-2R) levels had risen from 383 to 617 U/mL. Lymphoma progression
      involving an enlarged perigastric lymph node was also documented. This report
      illustrates a case of rapidly progressed intestinal follicular lymphoma,
      suggesting the possible usefulness of sIL-2R levels as an indicator of lymphoma
      progression. 

PMID- 24876982
TI  - Elbow dislocation with complete triceps avulsion.
AB  - Radio-ulnar Fracture dislocation of the elbow is a high-energy trauma which can
      be associated with significant ligamentous injury in adults. We report an unusual
      triad of injury in a patient with avulsion injury of the triceps. This injury can
      be thought of as a variant of "terrible triad" with dislocation of radio-ulnar
      joint, radial head fracture, and medial collateral ligament injury with avulsion
      of the triceps. Elbow has to be stabilized with early repair of the ligaments for
      a successful outcome. 

PMID- 24876981
TI  - Oral metastasis of metaplastic breast carcinoma in a patient with
      neurofibromatosis 1.
AB  - Neurofibromatosis type 1 (NF1) has been associated with an increased risk for
      development of malignancy, especially malignant peripheral nerve sheath tumors.
      In addition, recently, literature has demonstrated an increased risk of breast
      cancer in women with NF1. The present paper shows a 53-year-old woman with NF1
      who presented with metaplastic breast carcinoma and developed multiple
      metastases, including mandible. Furthermore, we reviewed the English literature,
      found 63 cases showing the association between NF1 and breast cancer, and added
      one more case. The present study demonstrated an important association between
      NF1 and breast cancer. Until the present time, there has been only one case of
      metaplastic breast carcinoma associated with NF1. Curiously, in our case the oral
      metastasis corresponded to sarcomatous component of metaplastic breast carcinoma.

PMID- 24876983
TI  - Median nerve compression in carpal tunnel caused by a giant lipoma.
AB  - A lipoma is a common, benign soft-tissue tumor that rarely arises in the upper
      limb. When one does occur in the hand, the location of the lipoma can cause nerve
      compression, which can mimic carpal tunnel symptoms. Magnetic resonance imaging
      is the visualization modality of choice for diagnosis and surgical planning of
      lipomas. Surgical resection is recommended to relieve the neurological
      manifestations of this disease. The surgeon should always suspect liposarcoma
      first before voluminous, atypical, or recurrent tumors are considered. 

PMID- 24876984
TI  - Troubling toys: rare-Earth magnet ingestion in children causing bowel
      perforations.
AB  - Ingestion of foreign bodies in the pediatric population is common and magnet
      ingestion is known to cause a significant morbidity. Rare-earth magnets are small
      3-6 mm diameter spherical powerful magnets that are sold as popular desk toys for
      adults and were previously found in construction toys in attractive colors for
      children to play with. We describe 2 young healthy children who ingested rare
      earth magnets Buckyballs while playing with these magnetic toys and later
      presented in emergency with acute abdomen. Abdominal imaging revealed several (26
      and 5) pieces of rare-earth magnets in the bowel loops. Emergency surgical
      exploration revealed multiple gastrointestinal perforations and fistula formation
      at sites of bowel entrapment in between strong magnets apposed to one another. We
      highlight the potential dangers of rare-earth magnets in children and suggest
      increasing public awareness about risks involved in rare-earth magnets ingestion
      by children to overcome this serious public health issue. 

PMID- 24876985
TI  - A case of blau syndrome.
AB  - We present a case of systemic granulomatous disorder/Blau syndrome. A patient was
      seen at our clinic with a diagnosis of Juvenile Idiopathic Arthritis (JIA). He
      was diagnosed with polyarticular JIA when he was two years old, at that time
      primary manifestations included inflammation of the hand and wrist joints
      bilaterally, later he developed ocular symptoms, which were attributed to JIA. He
      had liver, skin, pulmonary manifestations, and diagnostic workup including biopsy
      revealed granulomatous inflammation of these sites. During the diagnostic workup,
      he had worsening of ocular complaints, retinal exam showed panuveitis with
      multifocal choroiditis. These ocular findings are not seen in JIA, this, along
      with his other systemic manifestations, led us to revisit the diagnosis.
      Laboratory testing for genetic mutation for Blau syndrome was done and came back
      positive. Now all of his systemic findings were placed under one umbrella of
      systemic granulomatous syndrome/Blau syndrome. Due to worsening of ocular
      manifestations, he was started on Adalimumab with marked improvement of ocular
      and systemic manifestations and is followed by team that consists of
      Rheumatologist, Ophthalmologist, and Gastroenterologist. 

PMID- 24876987
TI  - A prospective study of soft tissue tumors histocytopathology correlation.
AB  - Background. Soft tissue tumors are defined as nonepithelial extraskeletal tissue
      of the body exclusive of the reticuloendothelial system, glia, and supporting
      tissue of various parenchymal organs. The absence of recognizable tissue
      architectural patterns in cytological preparation makes diagnosis by FNAC more
      difficult. Aims. To assess the utility of FNAC in diagnosing soft tissue tumors
      and to determine their patterns compared with with the respective histopathology
      results. Materials and Methods. 150 cases of soft tissue tumors were included in
      this study for cytologic and histologic correlation. FNAC air dried smears were
      stained with Giemsa stain and 95% ethanol fixed smears were stained with
      Papanicolaou stain. The smears were studied for cytological diagnosis and were
      categorized as benign, suspicious of malignancy, and malignant along with
      specific subtyping of the lesion. All diagnostic FNAC results were compared for
      diagnostic concordance using histology results as the "gold standard." Results.
      The sensitivity, specificity, positive predictive value, negative predictive
      value, and efficiency were 70%, 100%, 97.90%, 100%, and 98%, respectively. P
      value was <0.0001 which shows statistically extreme significant correlation.
      Conclusion. FNAC is a very important preliminary diagnostic tool in palpable soft
      tissue lumps with high degree of correlation with the final histopathology
      report. 

PMID- 24876986
TI  - Cervical thymic cyst in an adult.
AB  - Cervical thymic cysts (CTCs) are unusual lesions, representing only 1% of cystic
      cervical masses. Diagnosis of this condition in adults is even rarer. We report a
      34-year-old female who presented with asymptomatic progressively growing left
      sided neck swelling. Neck ultrasound (US) showed a large cystic lesion with
      septation, compressing the ipsilateral vessels. Magnetic resonance imaging (MRI)
      confirmed the US findings. Surgical excision was performed which subsequently
      showed findings consistent with CTC. CTC in adult is extremely rare, with few
      reported cases identified in the literature. Thymic gland anomalies in the neck
      are the consequences of an arrest in the descent of the gland, sequestration of
      the thymic tissue, or failure of involution. The diagnosis of this condition is
      rarely done prior to surgical excision. The clinical presentation, radiologic
      imaging, surgical findings, and histologic appearance are all essential
      components to make the correct diagnosis of this very rare differential diagnosis
      of cystic lateral neck swelling. 

PMID- 24876988
TI  - Bolus-Infusion Delays of Alteplase during Thrombolysis in Acute Ischaemic Stroke
      and Functional Outcome at 3 Months.
AB  - Background. The efficacy of alteplase in acute ischaemic stroke (AIS) is highly
      time dependent. Hence, alteplase is administered as soon as possible with a bolus
      followed by an infusion. Delays between bolus and infusion may occur, but the
      extent of these delays and the impact on outcome are unclear. Aims. We
      investigated the extent of bolus-infusion delays and the relationship between
      delays and stroke outcome. Method. We reviewed medical records of 276 patients
      who received alteplase for AIS at our centre between April, 2008, and June, 2013.
      Complete demographic and clinical data including 3-month modified Rankin Score
      (mRS) from 229 patients were analysed comparing delays of 0-8 and >8 minutes.
      Results. Overall mean (SD) bolus-infusion delay was 9 (7) minutes. Baseline
      characteristics were similar apart from more severe strokes in delays >8 minutes.
      Three-month outcomes were not significantly different although delays >8 minutes
      had lower functional independence rate (mRS 0-1: 23.1% versus 28.1%; adjusted OR
      1.2 (95% CI 0.6 to 2.4, P = 0.68)) and higher mortality rate (18% versus 11%, OR
      1.0, 95% CI 0.6 to 1.7, P = 0.95). Conclusions. In this single centre series,
      bolus-infusion delays of alteplase in AIS were common and no effect of bolus
      infusion delays on independence and mortality was found. 

PMID- 24876990
TI  - Chemical Immobilization of Sloth Bears (Melursus ursinus) with Ketamine
      Hydrochloride and Xylazine Hydrochloride: Hematology and Serum Biochemical
      Values.
AB  - The present study was conducted to define the physiological responses of captive
      sloth bears immobilized with ketamine hydrochloride and xylazine hydrochloride
      and to determine and compare the values of hematology and serum biochemical
      parameters between sexes. A total of 15 sloth bears were immobilized using
      combination of ketamine hydrochloride and xylazine hydrochloride drugs at the
      dose rate of 5.0 milligram (mg) per kg body weight and 2.0 mg per kg body weight,
      respectively. The use of combination of these drugs was found satisfactory for
      the chemical immobilization of captive sloth bears. There were no significant
      differences observed in induction time and recovery time and physiological
      parameters such as heart rate, respiratory rate, and rectal temperature between
      sexes. Health related parameters comprising hematological values like packed cell
      volume (PCV), hemoglobin (Hb), red blood cell count (RBC), erythrocyte indices,
      and so forth and biochemical values like total protein, blood urea nitrogen
      (BUN), creatinine, alkaline amino-transferase (ALT), aspartate amino-transferase
      (AST), and so forth were estimated in 11 (5 males and 6 females) apparently
      healthy bears. Comparison between sexes revealed significant difference in PCV (P
      < 0.05) and mean corpuscular hemoglobin concentration (MCHC) (P < 0.05). The
      study might help to evaluate health profiles of sloth bears for appropriate line
      treatment. 

PMID- 24876989
TI  - Current Perspectives on Mycobacterium farcinogenes and Mycobacterium senegalense,
      the Causal Agents of Bovine Farcy.
AB  - Mycobacterium farcinogenes and M. senegalense are the causal agents of bovine
      farcy, a chronic, progressive disease of the skin and lymphatics of zebu cattle.
      The disease, which is prevalent mainly in sub-Saharan Africa, was in earlier
      times thought to be caused by Nocardia farcinica and can be described as one of
      the neglected diseases in cattle. Some aspects of the disease have been
      investigated during the last five decades but the major development had been in
      the bacteriological, chemotaxonomic, and phylogenetic aspects. Molecular analyses
      confirmed that M. farcinogenes and M. senegalense fall in a subclade together
      with M. houstonense and M. fortuitum. This subclade is closely related to the one
      accommodating M. peregrinum, M. porcinum, M. septicum, M. neworleansense, and M.
      alvei. DNA probes were designed from 16S-23S rRNA internal transcribed spacer and
      could be used for the rapid diagnosis of bovine farcy. An ELISA assay has been
      evaluated for the serodiagnosis of the disease. The zoonotic potentials of M.
      farcinogenes and M. senegalense are unknown; few studies reported the isolation
      of M. senegalense and M. farcinogenes from human clinical sources but not from
      environmental sources or from other domestic or wild animals. 

PMID- 24876991
TI  - Antioxidant Potential of the Polyherbal Formulation "ImmuPlus": A Nutritional
      Supplement for Horses.
AB  - In order to counteract harmful effects of oxidative stress due to pathological
      conditions or physical exercise, horses are often administered dietary
      supplements having supposed high antioxidant activities. The aim of the present
      study was to identify the in vitro antioxidant potential of "ImmuPlus", a
      polyherbal formulation (Global Herbs LTD, Chichester, West Sussex, Great
      Britain), containing three medicinal plants (Withania somnifera, Tinospora
      cordifolia, and Emblica officinalis), known in Ayurveda for their use in human
      disease treatment. Extracts obtained by different solvents (water, methanol,
      ethanol, acetone, and hexane) were tested for total antioxidant capacity, total
      reducing power, scavenging activity against DPPH radical, and total polyphenol
      and flavonoid contents. Our results showed that, except as regards hexane, all
      the used solvents are able to extract compounds having high antioxidant activity,
      even when compared to ascorbic acid. Regression analysis showed significant
      correlations between antioxidant properties and polyphenol/flavonoid contents,
      indicating the latter, known for their beneficial effects on health of human and
      animal beings, as major components responsible for the strong antioxidant
      capacities. Moreover, obtained results suggest the effective role of the
      polyherbal mixture as good source of antioxidants in horses. 

PMID- 24876992
TI  - Genes Encoding Toxin of Clostridium difficile in Children with and without
      Diarrhea.
AB  - The presence of gene 16S rRNA and genes encoding toxin A (tcdA), toxin B (tcdB),
      and binary toxin (cdtA/cdtB) of Clostridium difficile in stool samples from
      children with (110) and without (150) diarrhea was determined by using a TaqMan
      system. Fifty-seven (21.9%) out of 260 stool samples harbored the 16S rRNA gene.
      The genetic profile of tcdA+/tcdB- and cdtA+/cdtB+ was verified in one C.
      difficile-positive diarrhea sample and of tcdA+/tcdB+ in three C. difficile
      positive nondiarrhea samples. The presence of tcdA+/tcdB+ in stools obtained from
      children without diarrhea, suggests that they were asymptomatic carriers of
      toxigenic strains. 

PMID- 24876994
TI  - Exogenous pulmonary surfactant as a vehicle for antimicrobials: assessment of
      surfactant-antibacterial interactions in vitro.
AB  - Owing to its unique surface-active properties, an exogenous pulmonary surfactant
      may become a promising drug delivery agent, in particular, acting as a vehicle
      for antibiotics in topical treatment of pneumonia. The purpose of this study was
      to assess a mutual influence of natural surfactant preparation and three
      antibiotics (amikacin, cefepime, and colistimethate sodium) in vitro and to
      identify appropriate combination(s) for subsequent in vivo investigations of
      experimental surfactant/antibiotic mixtures. Influence of antibiotics on surface
      active properties of exogenous surfactant was assessed using the modified Pattle
      method. Effects of exogenous surfactant on antibacterial activity of
      antimicrobials against Staphylococcus aureus, Klebsiella pneumoniae, and
      Pseudomonas aeruginosa were evaluated using conventional microbiologic
      procedures. Addition of amikacin or cefepime to surfactant had no significant
      influence on surface-active properties of the latter. Obvious reduction of
      surface-active properties was confirmed for surfactant/colistimethate
      composition. When suspended with antibiotics, surfactant either had no impact on
      their antimicrobial activity (amikacin) or exerted mild to moderate influence
      (reduction of cefepime bactericidal activity and increase of colistimethate
      bacteriostatic activity against S. aureus and P. aeruginosa). Considering
      favorable compatibility profile, the surfactant/amikacin combination is advisable
      for subsequent investigation of joint surfactant/antibacterial therapy in animals
      with bacterial pneumonia. 

PMID- 24876993
TI  - Targeting mRNA for Alzheimer's and related dementias.
AB  - Brain deposition of the amyloid beta-protein (A beta ) and tau are characteristic
      features in Alzheimer's disease (AD). Mutations in the A beta precursor protein
      (APP) and a protease involved in A beta production from APP strongly argue for a
      pathogenic role of A beta in AD, while mutations in tau are associated with
      related disorders collectively called frontotemporal lobar degeneration (FTLD).
      Despite intense effort, therapeutic strategies that target A beta or tau have not
      yet yielded medications, suggesting that alternative approaches should be
      pursued. In recent years, our laboratory has studied the role of mRNA in AD and
      FTLD, specifically those encoding tau and the A beta -producing protease BACE1.
      As many FTLD-causing tau mutations destabilize a hairpin structure that regulates
      RNA splicing, we have targeted this structure with small molecules, antisense
      oligonucleotides, and small molecule-antisense conjugates. We have also
      discovered that microRNA interaction with the 3'-untranslated region of tau
      regulates tau expression. Regarding BACE1, we found that alternative splicing
      leads to inactive splice isoforms and antisense oligonucleotides shift splicing
      toward these inactive isoforms to decrease A beta production. In addition, a G
      quadruplex structure in the BACE1 mRNA plays a role in splice regulation. The
      prospects for targeting tau and BACE1 mRNAs as therapeutic strategies will be
      discussed. 

PMID- 24876995
TI  - The korean social life, health and aging project-health examination cohort.
AB  - The Korean Social Life, Health, and Aging Project (KSHAP) is a population-based
      longitudinal study of health determinants among elderly Koreans. The target
      population of the KSHAP are people aged 60 years or older and their spouses
      living in a rural community of Korea. A complete enumeration survey was conducted
      in the first wave of the KSHAP on 94.7% (814 of 860) of the target population
      between December 2011 and July 2012. The KSHAP-Health Examination (KSHAP-HE)
      cohort consists of 698 people who completed additional health examinations at a
      public health center (n=533) or at their home (n=165). Face-to-face
      questionnaires were used to interview participants on their demographics, social
      network characteristics, medical history, health behaviors, cognitive function,
      and depression symptoms. Health center examinations included anthropometric
      measures, body impedance analysis, resting blood pressure measurement, radial
      artery tonometry, bone densitometry, the timed up-and-go test, and fasting blood
      analysis. However, only anthropometric measures, blood pressure measurement, and
      non-fasting blood analysis were available for home health examinations.
      Collaboration is encouraged and access to the KSHAP baseline data will be
      available via the website of the Korean Social Science Data Archive
      (http://www.kossda.or.kr). 

PMID- 24876996
TI  - Cellular imaging of deep organ using two-photon Bessel light-sheet nonlinear
      structured illumination microscopy.
AB  - In vivo fluorescent cellular imaging of deep internal organs is highly
      challenging, because the excitation needs to penetrate through strong scattering
      tissue and the emission signal is degraded significantly by photon diffusion
      induced by tissue-scattering. We report that by combining two-photon Bessel light
      sheet microscopy with nonlinear structured illumination microscopy (SIM), live
      samples up to 600 microns wide can be imaged by light-sheet microscopy with 500
      microns penetration depth, and diffused background in deep tissue light-sheet
      imaging can be reduced to obtain clear images at cellular resolution in depth
      beyond 200 microns. We demonstrate in vivo two-color imaging of pronephric
      glomeruli and vasculature of zebrafish kidney, whose cellular structures located
      at the center of the fish body are revealed in high clarity by two-color two
      photon Bessel light-sheet SIM. 

PMID- 24876997
TI  - Quantitative monitoring of radiation induced skin toxicities in nude mice using
      optical biomarkers measured from diffuse optical reflectance spectroscopy.
AB  - Monitoring the onset of erythema following external beam radiation therapy has
      the potential to offer a means of managing skin toxicities via biological
      targeted agents - prior to full progression. However, current skin toxicity
      scoring systems are subjective and provide at best a qualitative evaluation.
      Here, we investigate the potential of diffuse optical spectroscopy (DOS) to
      provide quantitative metrics for scoring skin toxicity. A DOS fiberoptic
      reflectance probe was used to collect white light spectra at two probing depths
      using two short fixed source-collector pairs with optical probing depths
      sensitive to the skin surface. The acquired spectra were fit to a diffusion
      theory model of light transport in tissue to extract optical biomarkers
      (hemoglobin concentration, oxygen saturation, scattering power and slope) from
      superficial skin layers of nude mice, which were subjected to erythema inducing
      doses of ionizing radiation. A statistically significant increase in oxygenated
      hemoglobin (p < 0.0016) was found in the skin post-irradiation - confirming
      previous reports. More interesting, we observed for the first time that the
      spectral scattering parameters, A (p = 0.026) and k (p = 0.011), were an
      indicator of erythema at day 6 and could potentially serve as an early detection
      optical biomarker of skin toxicity. Our data suggests that reflectance DOS may be
      employed to provide quantitative assessment of skin toxicities following curative
      doses of external beam radiation. 

PMID- 24876998
TI  - Three-dimensional transillumination image reconstruction for small animal with
      new scattering suppression technique.
AB  - To realize three-dimensional (3D) optical imaging of the internal structure of an
      animal body, we have developed a new technique to reconstruct optical computed
      tomography (optical CT) images from two-dimensional (2D) transillumination
      images. In transillumination imaging of an animal body using near-infrared light,
      the image is blurred because of the strong scattering in the tissue. To overcome
      this problem, we propose a novel technique to apply the point spread function
      (PSF) for a light source located inside the medium to the transilluminated image
      of light-absorbing structure. The problem of the depth-dependence of PSF was
      solved in the calculation of the projection image in the filtered back-projection
      method. The effectiveness of the proposed technique was assessed in the
      experiments with a model phantom and a mouse. These analyses verified the
      feasibility of the practical 3D imaging of the internal light-absorbing structure
      of a small animal. 

PMID- 24876999
TI  - Diffuse reflectance optical topography: location of inclusions in 3D and
      detectability limits.
AB  - In the present contribution we investigate the images of CW diffusely reflected
      light for a point-like source, registered by a CCD camera imaging a turbid medium
      containing an absorbing lesion. We show that detection of MUa variations
      (absorption anomalies) is achieved if images are normalized to background
      intensity. A theoretical analysis based on the diffusion approximation is
      presented to investigate the sensitivity and the limitations of our proposal and
      a novel procedure to find the location of the inclusions in 3D is given and
      tested. An analysis of the noise and its influence on the detection capabilities
      of our proposal is provided. Experimental results on phantoms are also given,
      supporting the proposed approach. 

PMID- 24877000
TI  - Photo-induced processes in collagen-hypericin system revealed by fluorescence
      spectroscopy and multiphoton microscopy.
AB  - Collagen is the main structural protein and the key determinant of mechanical and
      functional properties of tissues and organs. Proper balance between synthesis and
      degradation of collagen molecules is critical for maintaining normal
      physiological functions. In addition, collagen influences tumor development and
      drug delivery, which makes it a potential cancer therapy target. Using second
      harmonic generation, two-photon excited fluorescence microscopy, and
      spectrofluorimetry, we show that the natural pigment hypericin induces
      photosensitized destruction of collagen-based tissues. We demonstrate that
      hypericin-mediated processes in collagen fibers are irreversible and may be used
      for the treatment of cancer and collagen-related disorders. 

PMID- 24877001
TI  - Basis pursuit deconvolution for improving model-based reconstructed images in
      photoacoustic tomography.
AB  - The model-based image reconstruction approaches in photoacoustic tomography have
      a distinct advantage compared to traditional analytical methods for cases where
      limited data is available. These methods typically deploy Tikhonov based
      regularization scheme to reconstruct the initial pressure from the boundary
      acoustic data. The model-resolution for these cases represents the blur induced
      by the regularization scheme. A method that utilizes this blurring model and
      performs the basis pursuit deconvolution to improve the quantitative accuracy of
      the reconstructed photoacoustic image is proposed and shown to be superior
      compared to other traditional methods via three numerical experiments. Moreover,
      this deconvolution including the building of an approximate blur matrix is
      achieved via the Lanczos bidagonalization (least-squares QR) making this approach
      attractive in real-time. 

PMID- 24877002
TI  - Hyperspectral and differential CARS microscopy for quantitative chemical imaging
      in human adipocytes.
AB  - In this work, we demonstrate the applicability of coherent anti-Stokes Raman
      scattering (CARS) micro-spectroscopy for quantitative chemical imaging of
      saturated and unsaturated lipids in human stem-cell derived adipocytes. We
      compare dual-frequency/differential CARS (D-CARS), which enables rapid imaging
      and simple data analysis, with broadband hyperspectral CARS microscopy analyzed
      using an unsupervised phase-retrieval and factorization method recently developed
      by us for quantitative chemical image analysis. Measurements were taken in the
      vibrational fingerprint region (1200-2000/cm) and in the CH stretch region (2600
      3300/cm) using a home-built CARS set-up which enables hyperspectral imaging with
      10/cm resolution via spectral focussing from a single broadband 5 fs Ti:Sa laser
      source. Through a ratiometric analysis, both D-CARS and phase-retrieved
      hyperspectral CARS determine the concentration of unsaturated lipids with
      comparable accuracy in the fingerprint region, while in the CH stretch region D
      CARS provides only a qualitative contrast owing to its non-linear behavior. When
      analyzing hyperspectral CARS images using the blind factorization into
      susceptibilities and concentrations of chemical components recently demonstrated
      by us, we are able to determine vol:vol concentrations of different lipid
      components and spatially resolve inhomogeneities in lipid composition with
      superior accuracy compared to state-of-the art ratiometric methods. 

PMID- 24877003
TI  - Scleral birefringence as measured by polarization-sensitive optical coherence
      tomography and ocular biometric parameters of human eyes in vivo.
AB  - The relationship between scleral birefringence and biometric parameters of human
      eyes in vivo is investigated. Scleral birefringence near the limbus of 21 healthy
      human eyes was measured using polarization-sensitive optical coherence
      tomography. Spherical equivalent refractive error, axial eye length, and
      intraocular pressure (IOP) were measured in all subjects. IOP and scleral
      birefringence of human eyes in vivo was found to have statistically significant
      correlations (r = -0.63, P = 0.002). The slope of linear regression was -2.4 *
      10(-2) deg/MUm/mmHg. Neither spherical equivalent refractive error nor axial eye
      length had significant correlations with scleral birefringence. To evaluate the
      direct influence of IOP to scleral birefringence, scleral birefringence of 16 ex
      vivo porcine eyes was measured under controlled IOP of 5-60 mmHg. In these ex
      vivo porcine eyes, the mean linear regression slope between controlled IOP and
      scleral birefringence was -9.9 * 10(-4) deg/MUm/mmHg. In addition, porcine
      scleral collagen fibers were observed with second-harmonic-generation (SHG)
      microscopy. SHG images of porcine sclera, measured on the external surface at the
      superior side to the cornea, showed highly aligned collagen fibers parallel to
      the limbus. In conclusion, scleral birefringence of healthy human eyes was
      correlated with IOP, indicating that the ultrastructure of scleral collagen was
      correlated with IOP. It remains to show whether scleral collagen ultrastructure
      of human eyes is affected by IOP as a long-term effect. 

PMID- 24877004
TI  - Laser induced surface acoustic wave combined with phase sensitive optical
      coherence tomography for superficial tissue characterization: a solution for
      practical application.
AB  - Mechanical properties are important parameters that can be used to assess the
      physiologic conditions of biologic tissue. Measurements and mapping of tissue
      mechanical properties can aid in the diagnosis, characterisation and treatment of
      diseases. As a non-invasive, non-destructive and non-contact method, laser
      induced surface acoustic waves (SAWs) have potential to accurately characterise
      tissue elastic properties. However, challenge still exists when the laser is
      directly applied to the tissue because of potential heat generation due to laser
      energy deposition. This paper focuses on the thermal effect of the laser induced
      SAW on the tissue target and provides an alternate solution to facilitate its
      application in clinic environment. The solution proposed is to apply a thin agar
      membrane as surface shield to protect the tissue. Transient thermal analysis is
      developed and verified by experiments to study the effects of the high energy
      Nd:YAG laser pulse on the surface shield. The approach is then verified by
      measuring the mechanical property of skin in a Thiel mouse model. The results
      demonstrate a useful step toward the practical application of laser induced SAW
      method for measuring real elasticity of normal and diseased tissues in
      dermatology and other surface epithelia. 

PMID- 24877005
TI  - Spatial characterization of corneal biomechanical properties with optical
      coherence elastography after UV cross-linking.
AB  - Corneal collagen cross-linking (CXL) is a clinical treatment for keratoconus that
      structurally reinforces degenerating ocular tissue, thereby limiting disease
      progression. Clinical outcomes would benefit from noninvasive methods to assess
      tissue material properties in affected individuals. Regional variations in tissue
      properties were quantified before and after CXL in rabbit eyes using optical
      coherence elastography (OCE) imaging. Low-amplitude (<1um) elastic waves were
      generated using micro air-pulse stimulation and the resulting wave amplitude and
      speed were measured using phase-stabilized swept-source OCE. OCE imaging
      following CXL treatment demonstrates increased corneal stiffness through faster
      elastic wave propagation speeds and lower wave amplitudes. 

PMID- 24877006
TI  - Towards simultaneous Talbot bands based optical coherence tomography and scanning
      laser ophthalmoscopy imaging.
AB  - We report a Talbot bands-based optical coherence tomography (OCT) system capable
      of producing longitudinal B-scan OCT images and en-face scanning laser
      ophthalmoscopy (SLO) images of the human retina in-vivo. The OCT channel employs
      a broadband optical source and a spectrometer. A gap is created between the
      sample and reference beams while on their way towards the spectrometer's
      dispersive element to create Talbot bands. The spatial separation of the two
      beams facilitates collection by an SLO channel of optical power originating
      exclusively from the retina, deprived from any contribution from the reference
      beam. Three different modes of operation are presented, constrained by the
      minimum integration time of the camera used in the spectrometer and by the galvo
      scanners' scanning rate: (i) a simultaneous acquisition mode over the two
      channels, useful for small size imaging, that conserves the pixel-to-pixel
      correspondence between them; (ii) a hybrid sequential mode, where the system
      switches itself between the two regimes and (iii) a sequential "on-demand" mode,
      where the system can be used in either OCT or SLO regimes for as long as
      required. The two sequential modes present varying degrees of trade-off between
      pixel-to-pixel correspondence and independent full control of parameters within
      each channel. Images of the optic nerve and fovea regions obtained in the
      simultaneous (i) and in the hybrid sequential mode (ii) are presented. 

PMID- 24877007
TI  - Measurement of cardiac output by use of noninvasively measured transient
      hemodilution curves with photoacoustic technology.
AB  - We present the theoretical basis and experimental verification for cardiac output
      measurements using noninvasively measured hemodilution curves afforded with an
      indicator dilution technique and the emerging photoacoustic technology. A
      photoacoustic system noninvasively tracks a transient hemodilution effect induced
      by a bolus of isotonic saline as an indicator. As a result, a photoacoustic
      indicator dilution curve is obtained, which allows to estimate cardiac output
      from the developed algorithm. The experiments with a porcine blood circulatory
      phantom system demonstrated the feasibility of this technology towards the
      development of a noninvasive cardiac output measurement system for patient
      monitoring. 

PMID- 24877008
TI  - Optical architecture design for detection of absorbers embedded in visceral fat.
AB  - Optically absorbing ducts embedded in scattering adipose tissue can be injured
      during laparoscopic surgery. Non-sequential simulations and theoretical analysis
      compare optical system configurations for detecting these absorbers. For
      absorbers in deep scattering volumes, trans-illumination is preferred instead of
      diffuse reflectance. For improved contrast, a scanning source with a large area
      detector is preferred instead of a large area source with a pixelated detector. 

PMID- 24877009
TI  - Separation of superficial and cerebral hemodynamics using a single distance time
      domain NIRS measurement.
AB  - In functional near-infrared spectroscopy (fNIRS) superficial hemodynamics can
      mask optical signals related to brain activity. We present a method to separate
      superficial and cerebral absorption changes based on the analysis of changes in
      moments of time-of-flight distributions and a two-layered model. The related
      sensitivity factors were calculated from individual optical properties. The
      method was validated on a two-layer liquid phantom. Absorption changes in the
      lower layer were retrieved with an accuracy better than 20%. The method was
      successfully applied to in vivo data and compared to the reconstruction of
      homogeneous absorption changes. 

PMID- 24877010
TI  - Real-time high resolution laser speckle imaging of cerebral vascular changes in a
      rodent photothrombosis model.
AB  - The study of hemodynamic and vascular changes following ischemic stroke is of
      great importance in the understanding of physiological and pathological processes
      during the thrombus formation. The photothrombosis model is preferred by
      researchers in stroke study for its minimal invasiveness, controllable infarct
      volume and lesion location. Nevertheless, there is a lack in high spatiotemporal
      resolution techniques for real time monitoring of cerebral blood flow (CBF)
      changes in 2D-profile. In this study, we implemented a microscopic laser speckle
      imaging (LSI) system to detect CBF and other vascular changes in the rodent model
      of photothrombotic stroke. Using a high resolution and high speed CCD (640 * 480
      pixels, 60 fps), online image registration technique, and automatic parabolic
      curve fitting, we obtained real time CBF and blood velocity profile (BVP) changes
      in cortical vessels. Real time CBF and BVP monitoring has been shown to reveal
      details of vascular disturbances and the stages of blood coagulation in
      photothrombotic stroke. Moreover, LSI also provides information on additional
      parameters including vessel morphologic size, blood flow centerline velocity and
      CBF spatiotemporal fluctuations, which are very important for understanding the
      physiology and neurovascular pathology in the photothrombosis model. 

PMID- 24877011
TI  - Cornea characterization using a combined multiphoton microscopy and optical
      coherence tomography system.
AB  - We present a multimodal imaging system which combines multiphoton microscopy and
      optical coherence tomography to visualize the morphological structures, and to
      quantify the refractive index (RI) and thickness of cornea. The morphological
      similarities and differences at different corneal layers across various species
      are identified. In the piscine and human corneas, the stromata exhibit thin
      fibers that indicate an overall collagen direction. Human corneas display
      collagen micro-folds which cause increased light attenuation. In the murine,
      porcine and bovine corneas, the stromata show interwoven collagen patterns. The
      Bowman's layer and the Descemet's membrane are also distinguished in some
      species. The RI and thicknesses are quantified for the epithelium and the stromal
      layers respectively, where the epithelium is found to have slightly higher RI
      than the stroma. The average epithelial and stromal RI are, respectively, 1.371
      +/- 0.016 and 1.360 +/- 0.008 for the murine corneas; 1.502 +/- 0.057 and 1.335
      +/- 0.011 for the piscine corneas; 1.433 +/- 0.023 and 1.357 +/- 0.013 for the
      human corneas; 1.476 +/- 0.091 and 1.343 +/- 0.013 for the porcine corneas; and
      1.400 +/- 0.007 and 1.376 +/- 0.003 for the bovine corneas. The multimodal system
      can potentially provide a comprehensive characterization of the cornea. 

PMID- 24877012
TI  - Prostate cancer detection using combined auto-fluorescence and light reflectance
      spectroscopy: ex vivo study of human prostates.
AB  - This study was conducted to evaluate the capability of detecting prostate cancer
      (PCa) using auto-fluorescence lifetime spectroscopy (AFLS) and light reflectance
      spectroscopy (LRS). AFLS used excitation at 447 nm with four emission wavelengths
      (532, 562, 632, and 684 nm), where their lifetimes and weights were analyzed
      using a double exponent model. LRS was measured between 500 and 840 nm and
      analyzed by a quantitative model to determine hemoglobin concentrations and light
      scattering. Both AFLS and LRS were taken on n = 724 distinct locations from both
      prostate capsular (nc = 185) and parenchymal (np = 539) tissues, including PCa
      tissue, benign peripheral zone tissue and benign prostatic hyperplasia (BPH), of
      fresh ex vivo radical prostatectomy specimens from 37 patients with high volume,
      intermediate-to-high-grade PCa (Gleason score, GS >=7). AFLS and LRS parameters
      from parenchymal tissues were analyzed for statistical testing and
      classification. A feature selection algorithm based on multinomial logistic
      regression was implemented to identify critical parameters in order to classify
      high-grade PCa tissue. The regression model was in turn used to classify PCa
      tissue at the individual aggressive level of GS = 7,8,9. Receiver operating
      characteristic curves were generated and used to determine classification
      accuracy for each tissue type. We show that our dual-modal technique resulted in
      accuracies of 87.9%, 90.1%, and 85.1% for PCa classification at GS = 7, 8, 9
      within parenchymal tissues, and up to 91.1%, 91.9%, and 94.3% if capsular tissues
      were included for detection. Possible biochemical and physiological mechanisms
      causing signal differences in AFLS and LRS between PCa and benign tissues were
      also discussed. 

PMID- 24877013
TI  - Shadowless-illuminated variable-angle TIRF (siva-TIRF) microscopy for the
      observation of spatial-temporal dynamics in live cells.
AB  - Total-internal-reflection fluorescence (TIRF) microscopy provides high optical
      sectioning capability and a good signal-contrast ratio for structures near the
      surfaces of cells. In recent years, several improvements have been developed,
      such as variable-angle TIRF (VA-TIRF) and spinning TIRF (sp-TIRF), which permit
      quantitative image analysis and address non-uniform scattering fringes,
      respectively. Here, we present a dual-color DMD-based shadowless-illuminated
      variable-angle TIRF (siva-TIRF) system that provides a uniform illumination
      field. By adjusting the incidence angle of the illuminating laser on the back
      focal plane (BFP) of the objective, we can rapidly illuminate biological samples
      in layers of various thicknesses in TIRF or hollow-cone epi-fluorescence mode.
      Compared with other methods of accomplishing VA-TIRF/sp-TIRF illumination, our
      system is simple to build and cost-effective, and it provides optimal multi-plane
      dual-color images. By showing spatiotemporal correlated movement of clathrin
      coated structures with microtubule filaments from various layers of live cells,
      we demonstrate that cortical microtubules are important spatial regulators of
      clathrin-coated structures. Moreover, our system can be used to prove superb
      axial information of three-dimensional movement of structures near the plasma
      membrane within live cells. 

PMID- 24877014
TI  - Automated three-dimensional reconstruction and morphological analysis of
      dendritic spines based on semi-supervised learning.
AB  - A dendritic spine is a small membranous protrusion from a neuron's dendrite that
      typically receives input from a single synapse of an axon. Recent research shows
      that the morphological changes of dendritic spines have a close relationship with
      some specific diseases. The distribution of different dendritic spine phenotypes
      is a key indicator of such changes. Therefore, it is necessary to classify
      detected spines with different phenotypes online. Since the dendritic spines have
      complex three dimensional (3D) structures, current neuron morphological analysis
      approaches cannot classify the dendritic spines accurately with limited features.
      In this paper, we propose a novel semi-supervised learning approach in order to
      perform the online morphological classification of dendritic spines. Spines are
      detected by a new approach based on wavelet transform in the 3D space. A small
      training data set is chosen from the detected spines, which has the spines
      labeled by the neurobiologists. The remaining spines are then classified online
      by the semi-supervised learning (SSL) approach. Experimental results show that
      our method can quickly and accurately analyze neuron images with modest human
      intervention. 

PMID- 24877015
TI  - Fully automated digital holographic processing for monitoring the dynamics of a
      vesicle suspension under shear flow.
AB  - We investigate the dynamics of a vesicle suspension under shear flow between
      plates using DHM with a spatially reduced coherent source. Holograms are grabbed
      at a frequency of 24 frames/sec. The distribution of the vesicle suspension is
      obtained after numerical processing of the digital holograms sequence resulting
      in a 4D distribution. Obtaining this distribution is not straightforward and
      requires special processing to automate the analysis. We present an original
      method that fully automates the analysis and provides distributions that are
      further analyzed to extract physical properties of the fluid. Details of the
      numerical implementation, as well as sample experimental results are presented. 

PMID- 24877016
TI  - Directional sensitivity of the retina: A layered scattering model of outer
      segment photoreceptor pigments.
AB  - Photoreceptor outer segments have been modeled as stacked arrays of discs or
      membrane infoldings containing visual pigments with light-induced dipole moments.
      Waveguiding has been excluded so fields diffract beyond the physical boundaries
      of each photoreceptor cell. Optical reciprocity is used to argue for identical
      radiative and light gathering properties of pigments to model vision. Two models
      have been introduced: one a macroscopic model that assumes a uniform pigment
      density across each layer and another microscopic model that includes the spatial
      location of each pigment molecule within each layer. Both models result in highly
      similar directionality at the pupil plane which proves to be insensitive to the
      exact details of the outer-segment packing being predominantly determined by the
      first and last contributing layers as set by the fraction of bleaching. The
      versatility of the microscopic model is demonstrated with an array of examples
      that includes the Stiles-Crawford effect, visibility of a focused beam of light
      and the role of defocus. 

PMID- 24877017
TI  - Optimal lens design and use in laser-scanning microscopy.
AB  - In laser-scanning microscopy often an off-the-shelf achromatic doublet is used as
      a scan lens which can reduce the available diffraction-limited field-of-view
      (FOV) by a factor of 3 and introduce chromatic aberrations that are scan angle
      dependent. Here we present several simple lens designs of superior quality that
      fully make use of high-NA low-magnification objectives, offering diffraction
      limited imaging over a large FOV and wavelength range. We constructed a two
      photon laser-scanning microscope with optimized custom lenses which had a near
      diffraction limit point-spread-function (PSF) with less than 3.6% variation over
      a 400 um FOV and less than 0.5 um lateral color between 750 and 1050 nm. 

PMID- 24877018
TI  - Use of colloidal quantum dots as a digitally switched swept light source for gold
      nanoparticle based hyperspectral microscopy.
AB  - We propose a method to utilize colloidal quantum dots (QDs) as a swept light
      source for hyperspectral microscopy. The use of QD allows for uniform multicolor
      emission which covers visible-NIR wavelengths. We used 8 colors of CdSe/ZnS and
      CdTe/ZnS colloidal quantum dots with the peak emission wavelengths from 520 nm to
      800 nm. The QDs are packed in a compact enclosure, composing a low-cost, solid
      state swept light source that can be easily used in most microscopes. Multicolor
      emission from the QDs is simply controlled by digitally switching excitation
      UVLEDs, eliminating the use of mechanically-driven gratings or filters. We used
      gold nanoparticles as optical markers for hyperspectral microscopy. Due to the
      effect of localized surface plasmon resonance, gold nanoparticles demonstrate
      size and shape-dependent absorption spectra. Employed in a standard microscope,
      the QD light source enabled multispectral absorption imaging of macrophage cells
      labeled with gold nanorods and nanospheres. 

PMID- 24877019
TI  - Optical assessment of the cardiac rhythm of contracting cardiomyocytes in vitro
      and a pulsating heart in vivo for pharmacological screening.
AB  - Our quest in the pathogenesis and therapies targeting human heart diseases
      requires assessment of the contractile dynamics of cardiac models of varied
      complexity, such as isolated cardiomyocytes and the heart of a model animal. It
      is hence beneficial to have an integral means that can interrogate both
      cardiomyocytes in vitro and a heart in vivo. Herein we report an application of
      dual-beam optical reflectometry to determine noninvasively the rhythm of two
      representative cardiac models-chick embryonic cardiomyocytes and the heart of
      zebrafish. We probed self-beating cardiomyocytes and revealed the temporally
      varying contractile frequency with a short-time Fourier transform. Our unique
      dual-beam setup uniquely records the atrial and ventricular pulsations of
      zebrafish simultaneously. To minimize the cross talk between signals associated
      with atrial and ventricular chambers, we particularly modulated the two probe
      beams at distinct frequencies and extracted the signals specific to individual
      cardiac chambers with phase-sensitive detection. With this setup, we determined
      the atrio-ventricular interval, a parameter that is manifested by the electrical
      conduction from the atrium to the ventricle. To demonstrate pharmacological
      applications, we characterized zebrafish treated with various cardioactive and
      cardiotoxic drugs, and identified abnormal cardiac rhythms and atrioventricular
      (AV) blocks of varied degree. In light of its potential capability to assess
      cardiac models both in vitro and in vivo and to screen drugs with cardioactivity
      or toxicity, we expect this approach to have broad applications ranging from
      cardiopharmacology to developmental biology. 

PMID- 24877020
TI  - Fabricating low cost and high performance elastomer lenses using hanging
      droplets.
AB  - Existing methods for low cost lenses using parallel mold stamping and high
      temperature reflow requires complex engineering controls to produce high quality
      lenses. These manufacturing techniques rely on expensive equipment. In this
      paper, we propose a low cost (< $ 0.01 per pc) flexible moldless lens fabrication
      method based on curing a hanging transparent polydimethylsiloxane (PDMS)
      elastomer droplet on a curved substrate. Additional deposition of hanging
      droplets in the same manner led to a substantial increase in the lens curvature
      and concomitant decrease in the focal length of the PDMS lenses down to ~2 mm.
      The shortest focal length lenses were shown to collimate light from a bare light
      emitting diode (LED) and image microscopic structures down to around 4 um with
      160x magnification. Our hanging droplet lens fabrication technique heralds a new
      paradigm in the manufacture of low cost, high performance optical lenses for the
      masses. Using these lenses, we were able to transform an ordinary commercial
      smartphone camera into a low-cost digital dermascope (60x magnification) that can
      readily visualize microscopic structures on skin such as sweat pores. 

PMID- 24877021
TI  - Glucose sensing by waveguide-based absorption spectroscopy on a silicon chip.
AB  - In this work, we demonstrate in vitro detection of glucose by means of a lab-on
      chip absorption spectroscopy approach. This optical method allows label-free and
      specific detection of glucose. We show glucose detection in aqueous glucose
      solutions in the clinically relevant concentration range with a silicon-based
      optofluidic chip. The sample interface is a spiral-shaped rib waveguide
      integrated on a silicon-on-insulator (SOI) photonic chip. This SOI chip is
      combined with micro-fluidics in poly(dimethylsiloxane) (PDMS). We apply aqueous
      glucose solutions with different concentrations and monitor continuously how the
      transmission spectrum changes due to glucose. Based on these measurements, we
      derived a linear regression model, to relate the measured glucose spectra with
      concentration with an error-of-fitting of only 1.14 mM. This paper explains the
      challenges involved and discusses the optimal configuration for on-chip
      evanescent absorption spectroscopy. In addition, the prospects for using this
      sensor for glucose detection in complex physiological media (e.g. serum) is
      briefly discussed. 

PMID- 24877022
TI  - An analytical method for predicting the geometrical and optical properties of the
      human lens under accommodation.
AB  - We present an analytical method to describe the accommodative changes in the
      human crystalline lens. The method is based on the geometry-invariant lens model,
      in which the gradient-index (GRIN) iso-indicial contours are coupled to the
      external shape. This feature ensures that any given number of iso-indicial
      contours does not change with accommodation, which preserves the optical
      integrity of the GRIN structure. The coupling also enables us to define the GRIN
      structure if the radii and asphericities of the external lens surfaces are known.
      As an example, the accommodative changes in lenticular radii and central
      thickness were taken from the literature, while the asphericities of the external
      surfaces were derived analytically by adhering to the basic physical conditions
      of constant lens volume and its axial position. The resulting changes in lens
      geometry are consistent with experimental data, and the optical properties are in
      line with expected values for optical power and spherical aberration. The aim of
      the paper is to provide an anatomically and optically accurate lens model that is
      valid for 3 mm pupils and can be used as a new tool for better understanding of
      accommodation. 

PMID- 24877023
TI  - Hybrid FMT-MRI applied to in vivo atherosclerosis imaging.
AB  - Combining Fluorescent Molecular Tomography (FMT) with anatomical imaging, e.g.
      MRI facilitates interpreting functional information. Furthermore, using a
      heterogeneous model for light propagation has been shown in simulations to be
      superior to homogeneous modeling to quantify fluorescence. Here, we present a
      combined FMT-MRI system and apply it to heart and aorta molecular imaging, a
      challenging area due to strong tissue heterogeneity and the presence of air-voids
      due to lungs. First investigating performance in a phantom and mouse corpse, the
      MRI-enabled heterogeneous models resulted in an improved quantification of
      fluorescence reconstructions. The system was then used in mice for in vivo
      atherosclerosis molecular imaging. Results show that, when using the
      heterogeneous model, reconstructions were in agreement with the ex vivo
      measurements. Therefore, the proposed system might serve as a powerful imaging
      tool for atherosclerosis in mice. 

PMID- 24877024
TI  - Intravital imaging of mouse colonic adenoma using MMP-based molecular probes with
      multi-channel fluorescence endoscopy.
AB  - Intravital imaging has provided molecular, cellular and anatomical insight into
      the study of tumor. Early detection and treatment of gastrointestinal (GI)
      diseases can be enhanced with specific molecular markers and endoscopic imaging
      modalities. We present a wide-field multi-channel fluorescence endoscope to
      screen GI tract for colon cancer using multiple molecular probes targeting matrix
      metalloproteinases (MMP) conjugated with quantum dots (QD) in AOM/DSS mouse
      model. MMP9 and MMP14 antibody (Ab)-QD conjugates demonstrate specific binding to
      colonic adenoma. The average target-to-background (T/B) ratios are 2.10 +/- 0.28
      and 1.78 +/- 0.18 for MMP14 Ab-QD and MMP9 Ab-QD, respectively. The overlap
      between the two molecular probes is 67.7 +/- 8.4%. The presence of false negative
      indicates that even more number of targeting could increase the sensitivity of
      overall detection given heterogeneous molecular expression in tumors. Our
      approach indicates potential for the screening of small or flat lesions that are
      precancerous. 

PMID- 24877025
TI  - Confocal Raman micro-spectroscopy for rapid and label-free detection of maleic
      acid-induced variations in human sperm.
AB  - Confocal Raman microspectroscopy is a valuable analytical tool in biological and
      medical research, allowing the detection of sample variations without external
      labels or extensive preparation. To determine whether this method can assess the
      effect of maleic acid on sperm, we prepared human sperm samples incubated in
      different concentrations of maleic acid, after which Raman spectra from the
      various regions of sperm cells were recorded. Following the maleic acid
      treatment, Raman spectra indicated significant changes. Combined with other
      means, we found that the structures and chemical compositions of sperm membranes
      were damaged, and even the sperm DNA was damaged by the incorporation of maleic
      acid. Thus, this technique can be used for detection and identification of maleic
      acid-induced changes in human sperm at a molecular level. Although this
      particular application of Raman microspectroscopy still requires further
      validation, it has potentially promise as a diagnostic tool for reproductive
      medicine. 

PMID- 24877026
TI  - Pristimerin Induces Apoptosis in Prostate Cancer Cells by Down-regulating Bcl-2
      through ROS-dependent Ubiquitin-proteasomal Degradation Pathway.
AB  - Pristimerin is a quinonemethide triterpenoid with the potential of a promising
      anticancer agent. Pristimerin (PM) has shown anticancer activity against a range
      of cancer cell lines, but its activity for prostate cancer has not been
      adequately investigated. In the present study we have examined the underlying
      mechanisms of the apoptotic response of the hormone-sensitive (LNCaP) and hormone
      refractory (PC-3) prostate cancer cell lines to PM. Treatment with PM induced
      apoptosis in both cell lines as characterized by increased annexin V-binding and
      cleavage of PARP-1 and procaspases-3 and -9. It also induced mitochondrial
      depolarization, cytochrome c release from mitochondria and generation of reactive
      oxygen species (ROS). Response to PM is regulated by Bcl-2 since it down
      regulated Bcl-2 expression and overexpression of Bcl-2 rendered prostate cancer
      cells resistant to PM. ROS plays a role in down-regulation of Bcl-2, since
      treatment with PM in the presence of various ROS modulators, e.g., n
      acetylcysteine (NAC), a general purpose antioxidant; diphenylene iodonium (DPI),
      a NADPH inhibitor; rotenone (ROT), a mitochondrial electron transport chain
      interrupter rotenone or MnTBAP, a O2 scavenger, attenuated the down-regulation of
      Bcl-2. Furthermore, ROS is also involved in the ubiquitination and proteasomal
      degradation of Bcl-2 as both of these events were blocked by O 2- scavenger
      MnTBAP. Thus, pristimerin induces apoptosis in prostate cancer cells
      predominately through the mitochondrial apoptotic pathway by inhibiting
      antiapoptic Bcl-2 through a ROS-dependent ubiquitin-proteasomal degradation
      pathway.

PMID- 24877027
TI  - Analysis of in situ diversity and population structure in Ethiopian cultivated
      Sorghum bicolor (L.) landraces using phenotypic traits and SSR markers.
AB  - Genetic diversity is a fundamental input for every plant breeding program,
      genetic resources conservation, and evolutionary studies. In situ diversity and
      population genetic structure of eight cultivated sorghum landrace populations
      were investigated in the center of origin, Ethiopia using seven phenotypic traits
      and 12 highly polymorphic sorghum SSR markers. In farmers' fields, DNA samples
      were collected using Whatman(r) plant saver card and quantitative phenotypic
      traits were measured from 160 individual plant samples belonging to the eight
      populations representing three diverse geographical regions. High diversity was
      observed among the various populations for the measured phenotypic traits. The 12
      SSR loci produced a total of 123 alleles of which 78 (63.41%) were rare
      (frequency <=0.05) with an average of 10.25 alleles per polymorphic locus. The
      polymorphism information content (PIC) was in the range 0.39-0.85 showing the
      good discriminatory power of the SSR loci used. Average observed heterozygosity
      and gene diversity across all populations and loci ranged 0.04-0.33 and 0.41
      0.87, respectively. Neighbor-joining and STRUCTURE analyses grouped the 160
      samples from the eight populations differently. AMOVA showed 54.44% of the
      variation to be within populations, 32.76% among populations within regions, and
      12.8% among the regions of origin. There was high divergence in the total
      populations (FST = 0.40) indicating low level of gene flow (Nm = 0.38), but high
      gene flow was also observed in some adjacent populations. The populations from
      Wello displayed close relationship with remote Gibe and Metekel populations
      indicating that the variation followed human migration patterns. Implications of
      the results for sorghum improvement and germplasm conservation are discussed. 

PMID- 24877028
TI  - Adsorptive treatment of brewery effluent using activated Chrysophyllum albidium
      seed shell carbon.
AB  - Chrysophyllum albidium seed shell, an abundant, biodegradable and inexpensive
      natural resource was used as a precursor to bioadsorbent production for the
      removal of suspended and dissolved particles (SDP) from initially coagulated
      Brewery Effluent (BRE). Influence of key parameters such as contact time,
      bioadsorbent dose, pH and temperature were investigated using batch mode. The
      thermal behavior studies were evaluated using Thermogravimetric and Differential
      scanning calorimetric analyses. The morphological observations and functional
      groups of the bioadsorbents were determined using scanning electron microscopy
      and Fourier transform infrared spectroscopy, respectively. The adsorption
      equilibrium, thermodynamics and kinetic of SDP adsorption on H3PO4-treated shell
      and NH4Cl-treated shell were examined at specified temperatures. Equilibrium data
      sufficiently fitted the Langmuir isotherm model (R (2) > 0.99; SSE < 0.09). The
      pseudo-second order kinetic model provided the best correlation (R (2) > 0.99;
      SSE < 0.14) with the experimental data. The values of DeltaG degrees  and DeltaH
      degrees  indicated the spontaneous and endothermic nature of the process. This
      study demonstrated that C. albidium seed shell could be utilized as low cost,
      renewable, ecofriendly bioadsorbent for the uptake of SDP from BRE. 

PMID- 24877029
TI  - Assessment of the reliability of reproducing two-dimensional resistivity models
      using an image processing technique.
AB  - This study attempts to combine the results of geophysical images obtained from
      three commonly used electrode configurations using an image processing technique
      in order to assess their capabilities to reproduce two-dimensional (2-D)
      resistivity models. All the inverse resistivity models were processed using the
      PCI Geomatica software package commonly used for remote sensing data sets.
      Preprocessing of the 2-D inverse models was carried out to facilitate further
      processing and statistical analyses. Four Raster layers were created, three of
      these layers were used for the input images and the fourth layer was used as the
      output of the combined images. The data sets were merged using basic statistical
      approach. Interpreted results show that all images resolved and reconstructed the
      essential features of the models. An assessment of the accuracy of the images for
      the four geologic models was performed using four criteria: the mean absolute
      error and mean percentage absolute error, resistivity values of the reconstructed
      blocks and their displacements from the true models. Generally, the blocks of the
      images of maximum approach give the least estimated errors. Also, the
      displacement of the reconstructed blocks from the true blocks is the least and
      the reconstructed resistivities of the blocks are closer to the true blocks than
      any other combined used. Thus, it is corroborated that when inverse resistivity
      models are combined, most reliable and detailed information about the geologic
      models is obtained than using individual data sets. 

PMID- 24877030
TI  - Performance and sex difference in ultra-triathlon performance from Ironman to
      Double Deca Iron ultra-triathlon between 1978 and 2013.
AB  - It was assumed that women would be able to outperform men in ultra-marathon
      running. The present study investigated the sex difference in performance for all
      ultra-triathlon distances from the Ironman distance (i.e. 3.8 km swimming, 180 km
      cycling and 42 km running) in the 'Ironman Hawaii' to the Double Deca Iron ultra
      triathlon distance (i.e. 76 km swimming, 3,600 km cycling and 840 km running)
      between 1978 and 2013. The changes in performance and in the sex difference in
      performance for the annual three fastest finishers were analysed using linear,
      non-linear and multi-variate regression analyses from 46,123 athletes (i.e. 9,802
      women and 46,123 men). Women accounted for 11.9 +/- 5.8% of the total field and
      their percentage was highest in 'Ironman Hawaii' (22.1%) and lowest in Deca Iron
      ultra-triathlon (6.5%). In 'Ironman Hawaii', the sex difference decreased non
      linearly in swimming, cycling, running and overall race time. In Double Iron
      ultra-triathlon, the sex difference increased non-linearly in overall race time.
      In Triple Iron ultra-triathlon, the sex difference increased non-linearly in
      cycling and overall race time but linearly in running. For the three fastest
      finishers ever, the sex difference in performance showed no change with
      increasing race distance with the exception for the swimming split where the sex
      difference increased with increasing race distance (r(2) = 0.93, P = 0.001). The
      sex differences for the three fastest finishers ever for swimming, cycling,
      running and overall race times for all distances from Ironman to Deca Iron ultra
      triathlon were 27.0 +/- 17.8%, 24.3 +/- 9.9%, 24.5 +/- 11.0%, and 24.0 +/- 6.7%,
      respectively. To summarize, these findings showed that women reduced the sex
      difference in the shorter ultra-triathlon distances (i.e. Ironman distance) but
      extended the sex difference in longer distances (i.e. Double and Triple Iron
      ultra-triathlon). It seems very unlikely that women will ever outperform men in
      ultra-triathlons from Ironman to Double Iron ultra-triathlon. 

PMID- 24877031
TI  - LAP degradation product reflects plasma kallikrein-dependent TGF-beta activation
      in patients with hepatic fibrosis.
AB  - Byproducts of cytokine activation are sometimes useful as surrogate biomarkers
      for monitoring cytokine generation in patients. Transforming growth factor (TGF)
      beta plays a pivotal role in pathogenesis of hepatic fibrosis. TGF-beta is
      produced as part of an inactive latent complex, in which the cytokine is trapped
      by its propeptide, the latency-associated protein (LAP). Therefore, to exert its
      biological activity, TGF-beta must be released from the latent complex. Several
      proteases activate latent TGF-beta by cutting LAP. We previously reported that
      Camostat Mesilate, a broad spectrum protease inhibitor, which is especially
      potent at inhibiting plasma kallikrein (PLK), prevented liver fibrosis in the
      porcine serum-induced liver fibrosis model in rats. We suggested that PLK may
      work as an activator of latent TGF-beta during the pathogenesis of liver diseases
      in the animal models. However, it remained to be elucidated whether this
      activation mechanism also functions in fibrotic liver in patients. Here, we
      report that PLK cleaves LAP between R(58) and L(59) residues. We have produced
      monoclonal antibodies against two degradation products of LAP (LAP-DP) by PLK,
      and we have used these specific antibodies to immunostain LAP-DP in liver tissues
      from both fibrotic animals and patients. The N-terminal side LAP-DP ending at
      R(58) (R(58) LAP-DP) was detected in liver tissues, while the C-terminal side LAP
      DP beginning at L(59) (L(59) LAP-DP) was not detectable. The R(58) LAP-DP was
      seen mostly in alpha-smooth muscle actin-positive activated stellate cells. These
      data suggest for the first time that the occurrence of a PLK-dependent TGF-beta
      activation reaction in patients and indicates that the LAP-DP may be useful as a
      surrogate marker reflecting PLK-dependent TGF-beta activation in fibrotic liver
      both in animal models and in patients. 

PMID- 24877032
TI  - Post-treatment neutrophil-to-lymphocyte ratio in predicting prognosis in patients
      with metastatic clear cell renal cell carcinoma receiving sunitinib as first line
      therapy.
AB  - PURPOSE: Neutrophil-to-lymphocyte ratio (NLR) was evaluated as a prognostic
      factor in patients with metastatic clear cell renal cell carcinoma (RCC)
      receiving sunitinib as first line therapy. METHODS: Between December 2005 and
      December 2011, 109 patients with metastatic clear cell RCC were treated with
      sunitinib. The values of NLR were assessed at two time points: at baseline (pre
      treatment) and on day 1 of the second cycle (post-treatment). The prognostic
      significance of NLR on treatment outcome was evaluated with adjustment for known
      confounding risk factors. RESULTS: The median follow-up duration after sunitinib
      treatment was 24 months. There was no association between the pre-treatment NLR
      and tumor response (median pre-treatment NLRs: 2.2 for partial response [PR], 2.3
      for stable disease [SD], and 1.9 for progressive disease [PD]; p = 0.531).
      However, lower post-treatment NLR (1.1 for PR, 1.2 for SD, 2.3 for PD; p = 0.021)
      and larger reduction in NLR after treatment (-45.8% for PR, -45.6% for SD, 14.8%
      for PD; p = 0.009) was significantly associated with a better tumor response.
      When the patients were divided into two subgroups according to the cutoff value
      of the post-treatment NLR 1.1, the differences in median cancer-specific survival
      were observed between subgroups (not reached vs. 19.0 months, p = 0.012). In
      multivariate analysis, body mass index, MSKCC risk group, serum hemoglobin, and
      post-treatment NLR were significantly associated with cancer-specific mortality.
      CONCLUSIONS: Higher post-treatment NLR was associated with poor prognosis. An
      early reduction in the NLR after sunitinib treatment may indicate survival
      benefit in patients with metastatic clear cell RCC.

PMID- 24877034
TI  - Application of the generalized shift operator to the Hankel transform.
AB  - It is well known that the Hankel transform possesses neither a shift-modulation
      nor a convolution-multiplication rule, both of which have found many uses when
      used with other integral transforms. In this paper, the generalized shift
      operator, as defined by Levitan, is applied to the Hankel transform. It is shown
      that under this generalized definition of shift, both convolution and shift
      theorems now apply to the Hankel transform. The operation of a generalized shift
      is compared to that of a simple shift via example. 

PMID- 24877033
TI  - MiT translocation renal cell carcinomas: two subgroups of tumours with
      translocations involving 6p21 [t (6; 11)] and Xp11.2 [t (X;1 or X or 17)].
AB  - INTRODUCTION: MiT translocation renal cell carcinomas (TRCC) predominantly occur
      in younger patients with only 25% of patients being over 40 years. TRCC contains
      two main subgroups with translocations involving 6p21 or Xp11.2. Herein we
      present 10 cases. MATERIALS: Eight cases were treated at main author's
      institution (identified among 1653 (0.48%) cases of kidney tumours in adults).
      Two cases were retrieved from the Pilsen (CZ) Tumour Registry. RESULTS: Six cases
      were type Xp11.2 and four 6p21; 7 female, 3 male patients; Xp11.2 4:2, 6p21 3:1.
      The mean age 49 years (range: 21-80), 5 patients (50%) over 40 years. The mean
      age of the group with Xp11.2 TRCCs was 55 (median 51) and 6p21 41 (32) years. One
      female with a 6p21 tumour (24 years) underwent nephrectomy at 4 months of
      pregnancy. Stage (UICC, 7th ed. 2009) was 5xI, 3xIII, 2xIV. The mean size of
      tumour was 80 (40-165) mm. The mean follow-up was 33.2 (1-92) months. In patients
      with 6p21 tumours, one (25%) died after 3 months due to widely metastatic
      disease. In patients with Xp11.2 tumours, 3 (50%) succumbed due to metastatic
      disease (range 1-8 months). Three patients with Xp11.2 are alive at 7, 52 and 92
      months of follow-up, were diagnosed at early stage (T1a). CONCLUSION: TRCCs were
      more common in females. Patient with 6p21 tumours were younger than those with
      Xp11.2. Both types have definitive malignant potential Type Xp11.2 seems to be a
      more aggressive neoplasm than 6p21. The case with metastatic 6p21 tumour is the
      4th case described in the English literature.

PMID- 24877037
TI  - Popularization of exercise rehabilitation in the information age.

PMID- 24877035
TI  - Prospective, comprehensive, and effective viral monitoring in Cuban children
      undergoing solid organ transplantation.
AB  - PURPOSE: In Cuba, viral monitoring in the post-transplant period was not
      routinely performed. The aim of this research is to identify the most frequent
      viruses that affect transplanted Cuban children, by implementing a viral follow
      up during the post-transplant period. METHODS: The study population included all
      Cuban pediatric patients who underwent solid organ transplantation (SOT) between
      November 2009 and December 2012. A total of 34 transplanted pediatric patients of
      kidney (n = 11) and liver (n = 23) were prospectively monitored during a 34-week
      period for viral DNAemia and DNAuria by simultaneous detection of cytomegalovirus
      (CMV), Epstein-Barr virus, herpes simplex virus type 1 and 2, varicella zoster
      virus, human herpesvirus 6, human adenovirus, and polyomaviruses (BKV and JCV)
      using quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: Viral
      genome of at least one virus was detected in 21 of 34 recipients, 18 patients
      excreted virus in urine while 12 presented DNAemia. CMV (41.2%) and BKV (35.3%)
      were the most frequent viruses detected during the follow-up. CMV was the virus
      mainly associated with clinical symptoms and DNAemia. Its excretion in urine
      (with cut off value of 219 copies/mL) was associated with detection in plasma (p
      < 0.001); furthermore, CMV viruria was predictive of CMV viremia (OR:8.4, CI:2.4
      29.1, p = 0.001). There was no association between high viral load and clinical
      complications, due to the prompt initiation of preemptive ganciclovir.
      CONCLUSION: This comprehensive viral monitoring program effectively prevents the
      development of critical viral disease, thus urge the implementation of qRT-PCR as
      routine for viral monitoring of transplanted Cuban organ recipients.

PMID- 24877036
TI  - Adaptation of the African couples HIV testing and counseling model for men who
      have sex with men in the United States: an application of the ADAPT-ITT
      framework.
AB  - To respond to the need for new HIV prevention services for men who have sex with
      men (MSM) in the United States, and to respond to new data on the key role of
      main partnerships in US MSM epidemics, we sought to develop a new service for
      joint HIV testing of male couples. We used the ADAPT-ITT framework to guide our
      work. From May 2009 to July 2013, a multiphase process was undertaken to identify
      an appropriate service as the basis for adaptation, collect data to inform the
      adaptation, adapt the testing service, develop training materials, test the
      adapted service, and scale up and evaluate the initial version of the service. We
      chose to base our adaptation on an African couples HIV testing service that was
      developed in the 1980s and has been widely disseminated in low- and middle-income
      countries. Our adaptation was informed by qualitative data collections from MSM
      and HIV counselors, multiple online surveys of MSM, information gathering from
      key stakeholders, and theater testing of the adapted service with MSM and HIV
      counselors. Results of initial testing indicate that the adapted service is
      highly acceptable to MSM and to HIV counselors, that there are no evident harms
      (e.g., intimate partner violence, relationship dissolution) associated with the
      service, and that the service identifies a substantial number of HIV
      serodiscordant male couples. The story of the development and scale-up of the
      adapted service illustrates how multiple public and foundation funding sources
      can collaborate to bring a prevention adaptation from concept to public health
      application, touching on research, program evaluation, implementation science,
      and public health program delivery. The result of this process is an adapted
      couples HIV testing approach, with training materials and handoff from academic
      partners to public health for assessment of effectiveness and consideration of
      the potential benefits of implementation; further work is needed to optimally
      adapt the African couples testing service for use with male-female couples in the
      United States. 

PMID- 24877038
TI  - Role of adiponectin in metabolic and cardiovascular disease.
AB  - Under disease conditions including obesity (insulin resistance) and diabetes,
      dysregulation of adipokines such as tumor necrosis factor (TNF)-alpha, leptin,
      resistin, and adiponectin contribute to the development of metabolic and
      cardiovascular disease. Unlike other adipokines, adiponectin has been shown to be
      a therapeutic target for metabolic syndrome and cardiovascular disease.
      Circulating levels of adiponectin are markedly reduced in obese, diabetic,
      hypertensive, and coronary artery disease patients as well as experimental animal
      models of insulin resistance and diabetes. Recently, the small molecule
      adiponectin receptors (AdipoRs) agonist was discovered and suggested that the
      agonist is a novel therapeutic target for the treatment of type 2 diabetes linked
      to obesity in an experimental mouse model. This review will focus on signaling
      pathways involved in adiponectin and its receptors and the role of adiponectin in
      metabolic and cardiovascular disease including insulin resistance,
      cardiomyopathy, and cardiovascular dysfunction. 

PMID- 24877040
TI  - Swimming exercise ameliorates multiple sclerosis-induced impairment of short-term
      memory by suppressing apoptosis in the hippocampus of rats.
AB  - Multiple sclerosis is one of the autoimmune diseases in the central nervous
      system. Multiple sclerosis occurs through multiple mechanisms, and it is also
      mediated in part by an apoptotic mechanism. Swimming exercise has been
      recommended for the prevention and treatment of chronic diseases. In the present
      study, we investigated the effects of swimming exercise on short-term memory in
      relation with apoptotic neuronal cell death in the hippocampus following
      induction of multiple sclerosis. For this study, step-down avoidance task,
      terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)
      assay, immunohistochemistry for caspase-3 were performed. The animal model of
      multiple sclerosis was made by bilateral intracerebral ventricle injection of
      ethidium bromide. The rats in the swimming exercise groups were forced to swim
      for 30 min once daily for 14 consecutive days, starting 3 days after induction of
      multiple sclerosis. In the present results, short-term memory was deteriorated in
      the multiple sclerosis-induced rats. The number of TUNEL-positive and caspase-3
      positive cells in the hippocampal dentate gyrus was increased in the multiple
      sclerosis-induced rats. Swimming exercise alleviated multiple sclerosis-induced
      short-term memory impairment by suppressing apoptotic neuronal cell death in the
      hippocampus. These effects of swimming exercise may aid symptom relief in the
      incurable neurodegenerative diseases. 

PMID- 24877041
TI  - Duration-dependence of the effect of treadmill exercise on hyperactivity in
      attention deficit hyperactivity disorder rats.
AB  - Attention-deficit hyperactivity disorder (ADHD) is a common neurobehavioral
      disorder, and its symptoms are hyperactivity and deficits in learning and memory.
      Physical exercise increases dopamine synthesis and neuronal activity in various
      brain regions. In the present study, we investigate the duration-dependence of
      the treadmill exercise on hyperactivity in relation with dopamine expression in
      ADHD. Spontaneously hypertensive rats were used for the ADHD rats and Wistar
      Kyoto rats were used for the control rats. The rats in the exercise groups were
      forced to run on a treadmill for 10 min, 30 min, and 60 min once daily for 28
      consecutive days. For this experiment, open field test and immunohistochemistry
      for tyrosine hydroxylase were conducted. The present results revealed that ADHD
      rats showed hyperactivity, and tyrosine hydroxylase expression in the striatum
      and substantia nigra were decreased in ADHD rats. Treadmill exercise alleviated
      hyperactivity and also increased TH expression in ADHD rats. Treadmill exercise
      for 30 min per day showed most potent suppressing effect on hyperactivity, and
      this dose of treadmill exercise also most potently inhibited tyrosine hydroxylase
      expression. The present study suggests that treadmill exercise for 30 min once a
      day is the most effective therapeutic intervention for ADHD patients. 

PMID- 24877039
TI  - Effects of interventions on adiponectin and adiponectin receptors.
AB  - Adiponectin secreted from adipose tissue binds to two distinct adiponectin
      receptors (AdipoR1 and AdipoR2) identified and exerts its anti-diabetic effects
      in insulin-sensitive organs including liver, skeletal muscle and adipose tissue
      as well as amelioration of vascular dysfunction in the various vasculatures. A
      number of experimental and clinical observations have demonstrated that
      circulating levels of adiponectin are markedly reduced in obesity, type 2
      diabetes, hypertension, and coronary artery disease. Therapeutic interventions
      which can improve the action of adiponectin including elevation of circulating
      adiponectin concentration or up-regulation and/or activation of its receptors,
      could provide better understanding of strategies to ameliorate metabolic
      disorders and vascular disease. The focus of the present review is to summarize
      accumulating evidence showing the role of interventions such as pharmacological
      agents, exercise, and calorie restriction in the expression of adiponectin and
      adiponectin receptors. 

PMID- 24877042
TI  - Treadmill exercise alleviates impairment of spatial learning ability through
      enhancing cell proliferation in the streptozotocin-induced Alzheimer's disease
      rats.
AB  - Alzheimer's disease is the most common cause of dementia. This disease is a
      progressive and irreversible brain disorder accompanied with severe learning and
      memory impairment. Exercise increases cognitive ability, attenuates motor
      deficits, increases new neuron formation, and ameliorates neurological
      impairments in several neurodegenerative diseases. This study investigated the
      effects of treadmill exercise on spatial learning ability in relation with cell
      proliferation in the hippocampus. The rat model of Alzheimer's disease was
      induced by intracerebroventricular (ICV) injection of streptozotocin (STZ) using
      a stereotaxic instrument. The rats in the exercise groups were forced to run on a
      treadmill for once 30 min daily for 28 consecutive days starting at 3 days after
      the ICV injection of STZ. Radial 8-arm maze test was conducted for the spatial
      learning ability. New neuron formation in the hippocampus was detected by 5-bromo
      2'-deoxyuridine (BrdU) immunohistochemistry. Brain-derived neurotrophic factor
      (BDNF) and tyrosine kinase B (TrkB) expressions were examined by western blot
      analysis. The present results show that ICV injection of STZ impaired spatial
      learning ability. Decreased cell proliferation with decrement of BDNF and TrkB
      expressions in the hippocampus were observed in the STZ-induced Alzheimer's
      disease rats. However, treadmill exercise alleviated deficits of spatial learning
      ability. Treadmill exercise enhanced cell proliferation and increased BDNF and
      TrkB expressions in the rats with ICV injection of STZ. The present study
      suggests that treadmill exercise can be a useful strategy for treating memory
      impairment induced by several neurodegenerative diseases. 

PMID- 24877043
TI  - Effects of new sports tennis type exercise on aerobic capacity, follicle
      stimulating hormone and N-terminal telopeptide in the postmenopausal women.
AB  - Menopause is characterized by rapid decreases in bone mineral density, aerobic
      fitness, muscle strength, and balance. In the present study, we investigated the
      effects of new sports tennis type exercise on aerobic capacity, follicle
      stimulating hormone (FSH) and N-terminal telopeptide (NTX) in the postmenopausal
      women. Subjects were consisted of 20 postmenopausal women, who had not
      menstruated for at least 1 yr and had follicle-stimulating hormone levels > 35
      mIU/L, estradiol levels< 40 pg/mL. The subjects were randomly divided into two
      groups: control group (n= 10), new sports tennis type exercise group (n= 10). New
      sports tennis type exercise was consisted of warm up (10 min), new sports tennis
      type exercise (40 min), cool down (10 min) 3 days a per week for 12 weeks. The
      aerobic capacities were increased by 12 weeks new sports tennis type exercise.
      New sports tennis type exercise significantly increased FSH and NTx levels,
      indicating biochemical markers of bone formation and resorption. These findings
      indicate that 12 weeks of new sports tennis type exercise can be effective in
      prevention of bone loss and enhancement of aerobic capacity in postmenopausal
      women. 

PMID- 24877044
TI  - The effect of push factors in the leisure sports participation of the retired
      elderly on re-socialization recovery resilience.
AB  - This study aimed to provide useful materials for the realization of healthy and
      happy welfare society through the re-socialization of the retired elderly by
      identifying the effect of the push factors in the leisure sports participation of
      the retired elderly on re-socialization and recovery resilience. To achieve the
      study purpose, 304 subjects over the age of 55 residing in Seoul and Gyeonggin
      among the retired elderly were selected by using the method of systematic
      stratified cluster random sampling. As research methods, questionnaire papers
      were used. The data were collected and data which were judged to be incomplete or
      unreliable in responses were excluded from the analysis. After inputting data
      which are available to analysis and SPSS 18.0 program was used for statistical
      techniques. In this, data were processed by factor analysis, correlation
      analysis, and multiple regression analysis. The study results that were obtained
      from this analysis are as follows: First, the psychological stability among the
      push factors in the leisure sports participation of the elderly had a significant
      effect on re-socialization, while health pursuit had a significant effect on
      personal exchange and economic activity among the sub-factors of re
      socialization. Second, psychological stability among the push factors in the
      leisure sports participation of the retired elderly had a significant effect on
      recovery resilience; personal relationships had an effect on empathy skills,
      impulse control, and self-efficacy; and health pursuit had a significant effect
      on impulse control, optimism, and self-efficacy. 

PMID- 24877045
TI  - The preferential contraction ratios of transversus abdominis on the variations of
      knee angles during abdominal drawing-in maneuver in wall support standing.
AB  - The objective of this study was to determine appropriate knee angles for the
      abdominal drawing-in maneuver (ADIM) through evaluation of changes in contraction
      ratios of the abdominal muscles and activity of quadriceps muscle in relation to
      changes in knee angles occurring while the ADIM is performed in the wall support
      standing (WSS). 20 subjects performed the ADIM at different knee angles (0
      degrees , 20 degrees , 40 degrees , 60 degrees ) in random order, standing at a
      point 6 inches away from the wall with the spine maintained in the neutral
      position. The WSS with knee flexion at 20 degrees  showed significantly higher
      preferential contraction ratio (PCR) of transversus abdominis (TrA) compared to
      other positions (0 degrees , 40 degrees , 60 degrees ). Therefore, performing the
      ADIM in the WSS with knee flexion at 20 degrees  appears to be the most
      appropriate position for TrA PCR. 

PMID- 24877046
TI  - A study on the development of the protocol of leisure activity program for the
      elderly's deviant prevention.
AB  - The purpose of this study is to provide planning methods for leisure activity
      program to prevent the elderly's deviance, using the program components and
      protocol factors. This section discusses the results obtained through document
      analysis and Delphi technique. First, the components of leisure activity program
      were classified into five stages such as definition, condition analysis, program
      composition, application and evaluation. Second, the protocol factors in each
      stage of leisure activity program for the elderly's deviant prevention were 19
      main themes and 75 sub-themes respectively. In the stage of condition analysis,
      five main themes such as deviant prediction, individual, socio-demographic,
      social and cultural factors and 25 sub-themes were found. Program composition
      included three main themes, facilities, instructor and program and 16 sub-themes
      and in the application stage, there were three key themes, facilities, instructor
      and program and 14 sub-themes. Lastly, the evaluation found four main themes such
      as deviant prevention, participation in leisure activities, management and
      wellbeing and 16 sub-themes. 

PMID- 24877047
TI  - The relationships of elementary school students' sports participation with
      optimism, humor styles, and school life satisfaction.
AB  - The purpose of this study is to elucidate the relationships of children's sports
      participation with optimism, humor styles, and school life satisfaction. To
      achieve the study purpose, this study selected 150 subjects as a sample
      population among the elementary school senior students, currently participating
      in sports activities in metropolitan areas. As research methods, questionnaire
      papers were used and reliability analysis, factor analysis, correlation analysis,
      and multiple regression analysis were conducted by utilizing SPSS 18.0 after
      inputting analysis data into the computer. The study results, obtained in this
      study are as follows: First, the participation of children in sports had a
      significant effect on optimism. Second, in terms of the effect of children's
      sports participation on humor styles, participation frequency, participation
      period, and participation intensity in sports had a significant effect on
      affiliative humor, while participation period had an effect on enhancing humor
      among the sub-factors of humor styles. Third, in terms of the effect of
      children's sports participation on school life satisfaction, participation period
      had a significant effect on school life satisfaction; participation frequency had
      an effect on peer relations and regulation-observance; and participation
      intensity had an effect on peer relations and school life among the sub-factors
      of school life satisfaction. 

PMID- 24877048
TI  - Parents' perspectives and young athletes' perceptions of social support.
AB  - The purpose of this study was to examine experiences of being elite tennis
      players' parents, social support they provided to their children, and athletes'
      perceptions of influences of their parents' support. Four focus groups (2
      athletes and 2 parents groups) were conducted to collect data from both athletes
      and parents. The data were analyzed by thematic analysis and resulted in nine
      higher order themes including initiation of sporting career, expectations,
      satisfaction, parents' concerns, tangible, esteem, information, emotion, and
      network support. Later five themes which indicate kinds of support for athletes
      received from their parents were used to develop a matrix which can explain
      athletes' perceptions for each support they received from their parents. The
      findings revealed that there were some gaps between providers' and receivers'
      perspectives in effectiveness of provided support because some kinds of support
      were not effective when the support was provided without considering athletes
      needs. Therefore, the findings highlighted that support could be much effective
      if support providers for athletes consider athletes needs before they provide
      certain support to those athletes. 

PMID- 24877049
TI  - Effects of 16-week functional movement screen training program on strength and
      flexibility of elite high school baseball players.
AB  - Functional Movement Screen (FMS) is a way to pretest functional movement. This
      study examined the effects of the FMS training program on the strength and
      flexibility of 62 elite male high school baseball players (31 in the training
      group, 31 in the control group). All players who received less than two points on
      each FMS test item had to join the 16-week, three times weekly FMS training
      program. To analyze results among the FMS participants, measures including
      intraclass correlation coefficient (ICC) and repeated measure ANOVA were
      utilized. The Kappa coefficient was 0.805 when the intraclass correlation
      coefficient of the three participants was inspected. Strength showed a
      significant interaction depending on time and group (hand grip strength: P=0.011,
      bench press and squat both for one-repetition maximum (1RM): P=0.001 and P=0.008,
      respectively). Back muscle strength did not show a significant difference
      (P=0.660). Trunk forward flexion showed no interaction depending on time and
      groups (P=0.983) but trunk extension backward showed significant differences
      depending on groups (P=0.004) and time (P=0.001). Splits showed a significant
      difference depending on time and groups (P=0.004). The FMS training program
      improved the strength and flexibility of elite high school baseball players. 

PMID- 24877050
TI  - The effect of sustained natural apophyseal glides on headache, duration and
      cervical function in women with cervicogenic headache.
AB  - The objective of this study is to investigate the effect of sustained natural
      apophyseal glides (SNAGs) on pain and headache duration in women with
      cervicogenic headache. The method of this study is a single blind and randomized
      controlled trial. Forty patients with headache were divided randomly into the
      SNAGs group (n= 20), and control group (n= 20). The expectation of this study was
      that the SNAGs group, with facilitatory glide, has full range of movement without
      pain. Sustained end range holds or overpressure can be applied to the
      physiological movement and subjects in the control group received just light
      contact to the occipital area for the same amount of time as the SNAGs group,
      which is three times per week for a period of four weeks. Visual Analogue Scale
      (VAS), Headache Duration and Neck Disability Index (NDI) were evaluated by
      patients before and after the intervention. NDI in the SNAGs group showed
      significantly greater improvement, compared to the control group, in which only
      the SNAGS placebo technique was applied. In addition, a significantly greater
      improvement on the visual analogue scale was also observed in the SNAGs group
      compared with the control group (P< 0.05). In conclusion, the SNAGs technique can
      help middle aged female patients suffering from cervicogenic headache for relief
      of cervical pain and headache. It can also be used in physiotherapy on headache. 

PMID- 24877051
TI  - Effects of therapeutic massage on gait and pain after delayed onset muscle
      soreness.
AB  - Unfamiliar or sudden exercise can induce delayed onset muscle soreness (DOMS)
      within 12-24 h. So, several researchers have reported various interventions to
      treat DOMS. Massage is generally known to eliminate muscle fatigue. However,
      effect of massage after DOMS is still not clear. We investigated whether the
      massage is effective on pain and gait after DOMS. The participants were divided
      into a control group (n= 10) with DOMS and an experimental group (n= 11) with the
      massage treated after DOMS. We induced DOMS by taking isotonic exercise with
      going up and down 20 times in 5-story building. We applied the massage and
      assessment on gastrocnemius of dominant foot. The change of gait and pain was
      assessed using gaitrite and algometer. In the present results, the massage on
      gastrocnemius after DOMS showed significant difference in pain (P< 0.05). Also,
      there was a significant difference in gait (P< 0.05), especially, spatial
      parameters (distance, step length, stride length) and temporal parameters
      (ambulation, heel on off time, stride velocity). Moreover, the pain relief after
      massage-treated in DOMS correlated with gait. These results suggest that the
      massage on gastrocnemius after DOMS has influence on pain and gait performance.
      Therefore, massage can be applied as intervention for delayed onset muscle
      soreness. 

PMID- 24877052
TI  - Unipolar mania: recent updates and review of the literature.
AB  - Introduction. Unipolar mania (UM) has received less than the expected attention,
      when compared to its contemporary mood disorders, unipolar depression (UD) and
      bipolar disorder (BD). Method. The literature search included PUBMED and PSYCINFO
      databases. Cross-searches of key references were made to identify other articles
      of importance. Results. There seems to be a bipolar subgroup with a stable,
      unipolar recurrent manic course. Although UM does not have significant
      differences from bipolar mania in terms of sociodemographic variables, there are
      certain significant differences in clinical features. UM is reported to have more
      grandiosity, psychotic symptoms, and premorbid hyperthymic temperament, but less
      rapid cycling, suicidality, seasonality, and comorbid anxiety disorders. It seems
      to have a better course of illness with better social and professional
      adjustment. However, its response to lithium prophylaxis is found to be poor as
      compared to classical BD and valproate could be a better choice in this case.
      Conclusion. The available literature suggests that UM has certain differences
      from classical BD. The evidence, however, is insufficient to categorize it as
      separate diagnostic entity. However, considering UM as a course specifier of BD
      would be a reasonable step. 

PMID- 24877053
TI  - Value of fused 18F-Choline-PET/MRI to evaluate prostate cancer relapse in
      patients showing biochemical recurrence after EBRT: preliminary results.
AB  - PURPOSE: We compared the accuracy of (18)F-Choline-PET/MRI with that of
      multiparametric MRI (mMRI), (18)F-Choline-PET/CT, (18)F-Fluoride-PET/CT, and
      contrast-enhanced CT (CeCT) in detecting relapse in patients with suspected
      relapse of prostate cancer (PC) after external beam radiotherapy (EBRT). We
      assessed the association between standard uptake value (SUV) and apparent
      diffusion coefficient (ADC). METHODS: We evaluated 21 patients with biochemical
      relapse after EBRT. Patients underwent (18)F-Choline-PET/contrast-enhanced
      (Ce)CT, (18)F-Fluoride-PET/CT, and mMRI. Imaging coregistration of PET and mMRI
      was performed. RESULTS: (18)F-Choline-PET/MRI was positive in 18/21 patients,
      with a detection rate (DR) of 86%. DRs of (18)F-Choline-PET/CT, CeCT, and mMRI
      were 76%, 43%, and 81%, respectively. In terms of DR the only significant
      difference was between (18)F-Choline-PET/MRI and CeCT. On lesion-based analysis,
      the accuracy of (18)F-Choline-PET/MRI, (18)F-Choline-PET/CT, CeCT, and mMRI was
      99%, 95%, 70%, and 85%, respectively. Accuracy, sensitivity, and NPV of (18)F
      Choline-PET/MRI were significantly higher than those of both mMRI and CeCT. On
      whole-body assessment of bone metastases, the sensitivity of (18)F-Choline-PET/CT
      and (18)F-Fluoride-PET/CT was significantly higher than that of CeCT. Regarding
      local and lymph node relapse, we found a significant inverse correlation between
      ADC and SUV-max. CONCLUSION: (18)F-Choline-PET/MRI is a promising technique in
      detecting PC relapse.

PMID- 24877054
TI  - Predictors of memory and processing speed dysfunctions after traumatic brain
      injury.
AB  - BACKGROUND: The aims of this study were to evaluate the predictive value of
      admission Glasgow Coma Scale (GCS) scores, duration of unconsciousness,
      neurosurgical intervention, and countercoup lesion on the impairment of memory
      and processing speed functions six months after a traumatic brain injury (TBI)
      based on a structural equation modeling. METHODS: Thirty TBI patients recruited
      from Neurosurgical Department at the Kaohsiung Medical University Hospital were
      administered the Wechsler Memory Scale-III (WMS-III) and the Wechsler Adult
      Intelligence Scale-III processing speed index to evaluate the memory and
      processing speed functions. RESULTS: The study showed that GCS scores accounted
      for 40% of the variance in memory/processing speed. No significant predictive
      effects were found for the other three variables. GCS classification at the time
      of TBI seems to correspond moderately to the severity of memory/processing speed
      dysfunctions. CONCLUSIONS: The present study demonstrated that admission GCS
      score is a robust predictor of memory/processing speed dysfunctions after TBI.
      The results should be replicated with a large sample of patients with TBI, or be
      extended by examining other potential clinical predictors.

PMID- 24877055
TI  - The association among antioxidant enzymes, autoantibodies, and disease severity
      score in systemic lupus erythematosus: comparison of neuropsychiatric and
      nonneuropsychiatric groups.
AB  - BACKGROUND: Antioxidative capacity plays an important role in the severity of
      systemic lupus erythematosus (SLE), which is characterized by autoantibodies.
      This study aimed to determine the relationship among autoantibody titers,
      antioxidative stress reserve, and severity of SLE. METHODS: The autoantibody
      titers, clinical markers, antioxidant enzyme levels, and disease activity index
      (SLEDAI-2k) of 32 SLE patients and 16 healthy controls were compared. We also
      compared both the neuropsychiatric (NPSLE) and nonneuropsychiatric (non-NPSLE)
      groups. RESULTS: Superoxide dismutase in red blood cells was significantly lower
      in the SLE than in the control group. CRP levels are significant higher in SLE
      patients than in control group (P = 0.034). Among the autoantibodies, anti-U1RNP
      (P = 0.008), a-Sm (P = 0.027), and anti-ribosomal p (P = 0.028) significantly
      negatively correlated with glutathione levels. There has no significant
      correlation between SLE disease activity indexes (SLEDAI) and levels of C3, C4,
      and antioxidant enzymes. CONCLUSIONS: Erythrocyte superoxide dismutase is
      significantly lower in both NPSLE and non-NPSLE groups. SLE patients have both
      higher CRP and autoantibodies level and decreased superoxide dismutase level than
      the healthy control group.

PMID- 24877056
TI  - Inflammation-based scores: a new method for patient-targeted strategies and
      improved perioperative outcome in cancer patients.
AB  - Systemic inflammatory response (SIR) has actually been shown as an important
      prognostic factor associated with lower postoperative survival in several types
      of cancer. Thus, the challenge for physicians is to find specific, low-cost, and
      highly reliable inflammatory markers, clearly correlated with prognosis and able
      to preoperatively stratify patient's risk. Inflammation is a promising target to
      improve perioperative outcome, and data show that anti-inflammation techniques
      have a great potential in the perioperative period of cancer surgery.
      Inflammation scores could be useful to stratify patients with a potential better
      response to anti-inflammation strategies. Furthermore, inflammation scores could
      prevent failure of clinical trials by a better definition of patients to be
      included in such trials; inflammation scoring could clarify the real role of
      different drugs and techniques on outcome after cancer surgery, defining if
      different therapies are required for different patients. The role of this review
      is to focus on the currently available scores, in order to clarify their
      rationale and to analyze the actual evidence and limits, providing physicians
      with an updated overview of the possible inflammation-based prognostic scores for
      cancer patients undergoing surgery.

PMID- 24877057
TI  - Depressive symptoms in multiple sclerosis from an in vivo study with TBSS.
AB  - Clinically significant depression can impact up to 50% of patients with multiple
      sclerosis (MS) over a course of their life time, which is associated with an
      increased morbidity and mortality. In our study, fifteen relapsing-remitting MS
      (RRMS) patients and 15 age- and gender-matched normal controls were included.
      Diffusion tensor imaging (DTI) was acquired by employing a single-shot echo
      planar imaging sequence on a 3.0 T MR scanner and fractional anisotropy (FA) was
      performed with tract-based spatial statistics (TBSS) approach. Finally,
      widespread WM and GM abnormalities were observed in RRMS patients. Moreover, the
      relationships between the depressive symptoms which can be measured by Hamilton
      depression rating scale (HAMD) as well as clinical disabilities measured by the
      expanded disability status scale (EDSS) and FA changes were listed. There was a
      positive relation between EDSS and the FA changes in the right inferior parietal
      lobule, while negative relation was located in the left anterior cingulate cortex
      and hippocampus. Also a positive relation between HAMD and FA changes was found
      in the right posterior middle cingulate gyrus, the right hippocampus, the left
      hypothalamus, the right precentral gyrus, and the posterior cingulate which
      demonstrated a link between the depressive symptoms and clinically relevant brain
      areas in RRMS patients. 

PMID- 24877059
TI  - Evaluation of inhibitory effect of recreational drugs on dopaminergic terminal
      neuron by PET and whole-body autoradiography.
AB  - There is little investigation for the functional roles of peripheral dopamine.
      [(18)F]FDOPA has been used in cancer imaging (i.e., neuroendocrine and tumors
      pancreatic tumors) and neuroimaging (i.e., Parkinson's disease and Huntington's
      disease). Here, we accessed side effects of recreational drugs such as ketamine,
      cocaine, and methamphetamine on dopamine neurons in peripheral organs by using
      positron emission tomography (PET) imaging and quantitative whole-body
      autoradiography (QWBAR) with [(18)F]FDOPA. The images were applied for the
      measurement of specific binding ratios (SBRs) of striatum with the cerebellum as
      the reference region. Clear striatal [(18)F]FDOPA-derived radioactivity was
      observed. Moderate level of radiotracer accumulation was presented in the mucosal
      layers of the stomach and small intestine. The medulla layers of kidney had
      higher radioactivity than that of the cortex. Blocking images markedly eliminated
      the specific binding of [(18)F]FDOPA in the striatum and in peripheral organs
      such as stomachs, intestines, and kidney. Ketamine showed the highest inhibitory
      effect on striatal [(18)F]FDOPA-derived radioactivity followed by cocaine and
      methamphetamine. The current results demonstrated a useful crossing-validating
      tool that enhances the capability of [(18)F]FDOPA for further investigations of
      the alteration of dopaminergic neurons in the brain disorder or cancer diseases
      in peripheral tissues. 

PMID- 24877060
TI  - Pathogenesis of renal failure in multiple myeloma: any role of contrast media?
AB  - The spectrum of kidney disease-associated monoclonal immunoglobulin and plasma
      cell malignancies is remarkably broad and encompasses nearly all nephropathologic
      entities. Multiple myeloma with kidney impairment at presentation is a medical
      emergency since the recovery of kidney function is associated with survival
      benefits. In most cases, kidney impairment may be the first clinical
      manifestation of malignant plasma cell dyscrasias like multiple myeloma and light
      chain amyloidosis. Multiple myeloma per se cannot be considered a main risk
      factor for developing acute kidney injury following intravascular administration
      of iodinated contrast media. The risk is increased by comorbidities such as
      chronic kidney disease, diabetes, hypercalcemia, dehydration, and use of
      nephrotoxic drugs. Before the administration of contrast media, the current
      recommended laboratory tests for assessing kidney function are serum creatinine
      measurement and the estimation of glomerular filtration rate by using the CKD-EPI
      equation. The assessment of Bence Jones proteinuria is unnecessary for evaluating
      the risk of kidney failure in patients with multiple myeloma, since this test
      cannot be considered a surrogate biomarker of kidney function. 

PMID- 24877061
TI  - Inflammation based regulation of cancer cachexia.
AB  - Cancer cachexia, consisting of significant skeletal muscle wasting independent of
      nutritional intake, is a major concern for patients with solid tumors that
      affects surgical, therapeutic, and quality of life outcomes. This review
      summarizes the clinical implications, background of inflammatory cytokines, and
      the origin and sources of procachectic factors including TNF-alpha, IL-6, IL-1,
      INF-gamma, and PIF. Molecular mechanisms and pathways are described to elucidate
      the link between the immune response caused by the presence of the tumor and the
      final result of skeletal muscle wasting. 

PMID- 24877058
TI  - Involvement of DNA damage response pathways in hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) has been known as one of the most lethal human
      malignancies, due to the difficulty of early detection, chemoresistance, and
      radioresistance, and is characterized by active angiogenesis and metastasis,
      which account for rapid recurrence and poor survival. Its development has been
      closely associated with multiple risk factors, including hepatitis B and C virus
      infection, alcohol consumption, obesity, and diet contamination. Genetic
      alterations and genomic instability, probably resulted from unrepaired DNA
      lesions, are increasingly recognized as a common feature of human HCC.
      Dysregulation of DNA damage repair and signaling to cell cycle checkpoints, known
      as the DNA damage response (DDR), is associated with a predisposition to cancer
      and affects responses to DNA-damaging anticancer therapy. It has been
      demonstrated that various HCC-associated risk factors are able to promote DNA
      damages, formation of DNA adducts, and chromosomal aberrations. Hence,
      alterations in the DDR pathways may accumulate these lesions to trigger
      hepatocarcinogenesis and also to facilitate advanced HCC progression. This review
      collects some of the most known information about the link between HCC-associated
      risk factors and DDR pathways in HCC. Hopefully, the review will remind the
      researchers and clinicians of further characterizing and validating the roles of
      these DDR pathways in HCC. 

PMID- 24877062
TI  - Peripheral blood mononuclear cells as a laboratory to study dementia in the
      elderly.
AB  - The steady and dramatic increase in the incidence of Alzheimer's disease (AD) and
      the lack of effective treatments have stimulated the search for strategies to
      prevent or delay its onset and/or progression. Since the diagnosis of dementia
      requires a number of established features that are present when the disease is
      fully developed, but not always in the early stages, the need for a biological
      marker has proven to be urgent, in terms of both diagnosis and monitoring of AD.
      AD has been shown to affect peripheral blood mononuclear cells (PBMCs) that are a
      critical component of the immune system which provide defence against infection.
      Although studies are continuously supplying additional data that emphasize the
      central role of inflammation in AD, PBMCs have not been sufficiently investigated
      in this context. Delineating biochemical alterations in AD blood constituents may
      prove valuable in identifying accessible footprints that reflect degenerative
      processes within the Central Nervous System (CNS). In this review, we address the
      role of biomarkers in AD with a focus on the notion that PBMCs may serve as a
      peripheral laboratory to find molecular signatures that could aid in differential
      diagnosis with other forms of dementia and in monitoring of disease progression. 

PMID- 24877063
TI  - Bortezomib treatment produces nocifensive behavior and changes in the expression
      of TRPV1, CGRP, and substance P in the rat DRG, spinal cord, and sciatic nerve.
AB  - To investigate neurochemical changes associated with bortezomib-induced painful
      peripheral neuropathy (PN), we examined the effects of a single-dose intravenous
      administration of bortezomib and a well-established "chronic" schedule in a rat
      model of bortezomib-induced PN. The TRPV1 channel and sensory neuropeptides CGRP
      and substance P (SP) were studied in L4-L5 dorsal root ganglia (DRGs), spinal
      cord, and sciatic nerve. Behavioral measures, performed at the end of the chronic
      bortezomib treatment, confirmed a reduction of mechanical nociceptive threshold,
      whereas no difference occurred in thermal withdrawal latency. Western blot
      analysis showed a relative increase of TRPV1 in DRG and spinal cord after both
      acute and chronic bortezomib administration. Reverse transcriptase-polymerase
      chain reaction revealed a decrease of TRPV1 and CGRP mRNA relative levels after
      chronic treatment. Immunohistochemistry showed that in the DRGs, TRPV1-, CGRP-,
      and SP-immunoreactive neurons were mostly small- and medium-sized and the
      proportion of TRPV1- and CGRP-labeled neurons increased after treatment. A
      bortezomib-induced increase in density of TRPV1- and CGRP-immunoreactive
      innervation in the dorsal horn was also observed. Our findings show that
      bortezomib-treatment selectively affects subsets of DRG neurons likely involved
      in the processing of nociceptive stimuli and that neurochemical changes may
      contribute to development and persistence of pain in bortezomib-induced PN. 

PMID- 24877065
TI  - Mining seasonal marine microbial pattern with greedy heuristic clustering and
      symmetrical nonnegative matrix factorization.
AB  - With the development of high-throughput and low-cost sequencing technology, a
      large number of marine microbial sequences were generated. The association
      patterns between marine microbial species and environment factors are hidden in
      these large amount sequences. Mining these association patterns is beneficial to
      exploit the marine resources. However, very few marine microbial association
      patterns are well investigated in this field. The present study reports the
      development of a novel method called HC-sNMF to detect the marine microbial
      association patterns. The results show that the four seasonal marine microbial
      association networks have characters of complex networks, the same environmental
      factor influences different species in the four seasons, and the correlative
      relationships are stronger between OTUs (taxa) than with environmental factors in
      the four seasons detecting community. 

PMID- 24877064
TI  - A review on antibacterial, antiviral, and antifungal activity of curcumin.
AB  - Curcuma longa L. (Zingiberaceae family) and its polyphenolic compound curcumin
      have been subjected to a variety of antimicrobial investigations due to extensive
      traditional uses and low side effects. Antimicrobial activities for curcumin and
      rhizome extract of C. longa against different bacteria, viruses, fungi, and
      parasites have been reported. The promising results for antimicrobial activity of
      curcumin made it a good candidate to enhance the inhibitory effect of existing
      antimicrobial agents through synergism. Indeed, different investigations have
      been done to increase the antimicrobial activity of curcumin, including synthesis
      of different chemical derivatives to increase its water solubility as well ass
      cell up take of curcumin. This review aims to summarize previous antimicrobial
      studies of curcumin towards its application in the future studies as a natural
      antimicrobial agent. 

PMID- 24877066
TI  - Homocysteine serum levels in diabetic patients with non proliferative,
      proliferative and without retinopathy.
AB  - Homocysteine has been associated with extracellular matrix changes. The diabetic
      retinopathy is a neurovascular complication of diabetes mellitus and it is the
      leading cause of vision loss among working adults worldwide. In this study, we
      evaluate the role of homocysteine in diabetic retinopathy analyzing the plasma
      levels of homocysteine in 63 diabetic type 2 patients with nonproliferative
      retinopathy (NPDR), 62 patients with proliferative diabetic retinopathy (PDR), 50
      healthy subjects used as control group, and 75 randomly selected patients. 

PMID- 24877067
TI  - Evaluation of the DDSolver software applications.
AB  - When a new oral dosage form is developed, its dissolution behavior must be
      quantitatively analyzed. Dissolution analysis involves a comparison of the
      dissolution profiles and the application of mathematical models to describe the
      drug release pattern. This report aims to assess the application of the DDSolver,
      an Excel add-in software package, which is designed to analyze data obtained from
      dissolution experiments. The data used in this report were chosen from two
      dissolution studies. The results of the DDSolver analysis were compared with
      those obtained using an Excel worksheet. The comparisons among three different
      products obtained similarity factors (f 2) of 23.21, 46.66, and 17.91 using both
      DDSolver and the Excel worksheet. The results differed when DDSolver and Excel
      were used to calculate the release exponent "n" in the Korsmeyer-Peppas model.
      Performing routine quantitative analysis proved to be much easier using the
      DDSolver program than an Excel spreadsheet. The use of the DDSolver program
      reduced the calculation time and has the potential to omit calculation errors,
      thus making this software package a convenient tool for dissolution comparison. 

PMID- 24877068
TI  - The zoonotic risk of Ancylostoma ceylanicum isolated from stray dogs and cats in
      Guangzhou, South China.
AB  - Canine and feline hookworm infection is endemic in many countries with zoonotic
      transmission representing a potentially significant public health concern.
      However, there is limited data available on the zoonotic transmission of canine
      and feline hookworms in China. This study was conducted to evaluate the zoonotic
      risk of Ancylostoma ceylanicum isolated from stray dogs and cats in Guangzhou,
      south China. Primer pairs CAF/CAR were designed to amplify complete ITS sequences
      of obtained A. ceylanicum. The results were compared with fourteen ITS reference
      sequences of human-derived A. ceylanicum registered in GenBank, and phylogenetic
      trees were established by using NJ and ML methods. The sequence similarity of
      three dog-derived and five cat-derived A. ceylanicum with fourteen human-derived
      A. ceylanicum were 96.8%~100% and 97.8%~100%, respectively. Phylogenetic analysis
      placed A. ceylanicum isolated from dogs and cats in the same group with A.
      ceylanicum human isolates. Due to the ability of A. ceylanicum to cause a patent
      infection in humans, the zoonotic risk arising from dog and cat reservoirs to
      communities in this region should be determined. 

PMID- 24877069
TI  - Evolving ablative therapies for hepatic malignancy.
AB  - The liver is a common site for both primary and secondary malignancy. Hepatic
      resection and transplantation are the two treatment modalities that have been
      shown to achieve complete cure, but only 10 to 20% of patients are candidates for
      these treatments. For the remaining patients, tumor ablation has emerged as the
      most promising alternative modality. In addition to providing local control and
      improving survival outcomes, tumor ablation also helps to down stage patients for
      potential curative treatments, both alone as well as in combination with other
      treatments. While tumor ablation can be achieved in multiple ways, the
      introduction of newer ablative techniques has shifted the focus from palliation
      to potentially curative treatment. Because the long-term safety and survival
      benefits are not substantive at present, it is important that we strive to
      evaluate the results from these studies using appropriate comparative outcome
      methodologies. 

PMID- 24877070
TI  - Circulating conventional and plasmacytoid dendritic cell subsets display distinct
      kinetics during in vivo repeated allergen skin challenges in atopic subjects.
AB  - Upon allergen challenge, DC subsets are recruited to target sites under the
      influence of chemotactic agents; however, details pertinent to their trafficking
      remain largely unknown. We investigated the kinetic profiles of blood and skin
      infiltrating DC subsets in twelve atopic subjects receiving six weekly
      intradermal allergen and diluent injections. The role of activin-A, a cytokine
      induced in allergic and tissue repair processes, on the chemotactic profiles of
      DC subsets was also examined. Plasmacytoid (pDCs) and conventional DCs (cDCs)
      were evaluated at various time-points in the blood and skin. In situ activin-A
      expression was assessed in the skin and its effects on chemokine receptor
      expression of isolated cDCs were investigated. Blood pDCs were reduced 1 h after
      challenge, while cDCs decreased gradually within 24 h. Skin cDCs increased
      significantly 24 h after the first challenge, inversely correlating with blood
      cDCs. Activin-A in the skin increased 24 h after the first allergen challenge and
      correlated with infiltrating cDCs. Activin-A increased the CCR10/CCR4 expression
      ratio in cultured human cDCs. DC subsets demonstrate distinct kinetic profiles in
      the blood and skin especially during acute allergic inflammation, pointing to
      disparate roles depending on each phase of the inflammatory response. The effects
      of activin-A on modulating the chemotactic profile of cDCs suggest it may be a
      plausible therapeutic target for allergic diseases.

PMID- 24877072
TI  - Epidemiology of injuries in Belgium: contribution of hospital data for
      surveillance.
AB  - OBJECTIVES: Investigating injuries in terms of occurrences and patient and
      hospital stay characteristics. METHODS: 17370 stays, with at least one E code,
      were investigated based on data from 13 Belgian hospitals. Pearson's chi-square
      and Kruskal-Wallis tests were used to assess the variations between distributions
      of the investigated factors according to the injury's types. RESULTS: Major
      injuries were accidental falls, transport injuries, and self-inflicted injuries.
      There were more men in the transport injuries group and the accidental falls
      group was older. For the transport injuries, there were more arrivals with the
      support of a mobile intensive care unit and/or a paramedic intervention team and
      a general practitioner was more implicated for the accidental falls. In three
      quarters of cases, it was a primary diagnostic related to injury and poisoning
      which was made. The median length of stay was nearly equal to one week and for
      accidental falls, this value is three times higher. The median cost, from the
      social security point of view, for all injuries was equal to ? 1377 and there was
      a higher median cost within the falls group. CONCLUSION: This study based on
      hospitals data provides important information both on factors associated with and
      on hospital costs generated by injuries.

PMID- 24877071
TI  - Phenotypic and genotypic characterization of enterotoxigenic Escherichia coli
      clinical isolates from northern Colombia, South America.
AB  - Enterotoxigenic Escherichia coli (ETEC) are major causes of childhood diarrhea in
      low and middle income countries including Colombia, South America. To understand
      the diversity of ETEC strains in the region, clinical isolates obtained from
      northern Colombia children were evaluated for multiple locus sequencing typing,
      serotyping, classical and nonclassical virulence genes, and antibiotic
      susceptibility. Among 40 ETEC clinical isolates evaluated, 21 (52.5%) were
      positive for LT gene, 13 (32.5%) for ST gene, and 6 (15%) for both ST and LT. The
      most prevalent colonization surface antigens (CS) were CS21 and CFA/I identified
      in 21 (50%) and 13 (32.5%) isolates, respectively. The eatA, irp2, and fyuA were
      the most common nonclassical virulence genes present in more than 60% of the
      isolates. Ampicillin resistance (80% of the strains) was the most frequent
      phenotype among ETEC strains followed by trimethoprim-sulfamethoxazole resistance
      (52.5%). Based on multiple locus sequencing typing (MLST), we recognize that 6
      clonal groups of ETEC clinical isolates circulate in Colombia. ETEC clinical
      isolates from children in northern Colombia are highly diverse, yet some isolates
      circulating in the community belong to well-defined clonal groups that share a
      unique set of virulence factors, serotypes, and MLST sequence types. 

PMID- 24877073
TI  - Synchronous and metachronous breast malignancies: a cross-sectional retrospective
      study and review of the literature.
AB  - OBJECTIVE: There is increasing interest in patients with metachronous (MBC) and
      synchronous breast cancer (SBC). The objective of this study was to evaluate the
      occurrence and outcome of MBCs and SBCs. METHODS: A retrospective study on women
      operated in our department for breast cancer between 2002 and 2005 was carried
      out. Patients were divided into three groups: women with MBC, SBC, and unilateral
      breast cancer (UBC). Moreover, we performed a meta-analysis of the English
      literature about multiple breast cancers between 2000 and 2011 taking into
      consideration their prevalence and overall survival (OS). RESULTS: We identified
      584 breast cancer patients: 16 women (3%) presented SBC and 40 MBC (7%, second
      cancer after 72-month follow-up IQR 40-145). Although the meta-analysis showed
      significant OS differences between MBC or SBC and UBC, we did not observe any
      significant OS difference among the three groups of our population. Anyway, we
      found a significant worse disease-free survival in MBC than UBC and a significant
      higher prevalence of radical surgery in MBC and SBC than UBC. CONCLUSIONS:
      Despite the low prevalence of MBC and SBC, the presence of a long time risk of
      MBC confirms the crucial role of ipsi- and contralateral mammographies in the
      postoperative follow-up.

PMID- 24877074
TI  - Morphogenesis and production of enzymes by Penicillium echinulatum in response to
      different carbon sources.
AB  - The effect of different carbon sources on morphology and cellulase and xylanase
      production of Penicillium echinulatum was evaluated in this work. Among the six
      carbon sources studied, cellulose and sugar cane bagasse were the most suitable
      for the production of filter paper activity, endoglucanases, xylanases, and beta
      glucosidases. However, sucrose and glucose showed beta -glucosidase activities
      similar to those obtained with the insoluble sources. The polyacrylamide gels
      proved the enzymatic activity, since different standards bands were detected in
      the media mentioned above. Regarding morphology, it was observed that the
      mycelium in a dispersed form provided the greatest enzymatic activity, possibly
      due to greater interaction between the substrate and hyphae. These data are
      important in understanding the physiology of fungi and could contribute to
      obtaining enzyme with potential application in the technology of second
      generation ethanol.

PMID- 24877075
TI  - A founder large deletion mutation in Xeroderma pigmentosum-Variant form in
      Tunisia: implication for molecular diagnosis and therapy.
AB  - Xeroderma pigmentosum Variant (XP-V) form is characterized by a late onset of
      skin symptoms. Our aim is the clinical and genetic investigations of XP-V
      Tunisian patients in order to develop a simple tool for early diagnosis. We
      investigated 16 suspected XP patients belonging to ten consanguineous families.
      Analysis of the POLH gene was performed by linkage analysis, long range PCR, and
      sequencing. Genetic analysis showed linkage to the POLH gene with a founder
      haplotype in all affected patients. Long range PCR of exon 9 to exon 11 showed a
      3926 bp deletion compared to control individuals. Sequence analysis demonstrates
      that this deletion has occurred between two Alu-Sq2 repetitive sequences in the
      same orientation, respectively, in introns 9 and 10. We suggest that this
      mutation POLH NG_009252.1: g.36847_40771del3925 is caused by an equal crossover
      event that occurred between two homologous chromosomes at meiosis. These results
      allowed us to develop a simple test based on a simple PCR in order to screen
      suspected XP-V patients. In Tunisia, the prevalence of XP-V group seems to be
      underestimated and clinical diagnosis is usually later. Cascade screening of this
      founder mutation by PCR in regions with high frequency of XP provides a rapid and
      cost-effective tool for early diagnosis of XP-V in Tunisia and North Africa.

PMID- 24877076
TI  - OWL reasoning framework over big biological knowledge network.
AB  - Recently, huge amounts of data are generated in the domain of biology. Embedded
      with domain knowledge from different disciplines, the isolated biological
      resources are implicitly connected. Thus it has shaped a big network of versatile
      biological knowledge. Faced with such massive, disparate, and interlinked
      biological data, providing an efficient way to model, integrate, and analyze the
      big biological network becomes a challenge. In this paper, we present a general
      OWL (web ontology language) reasoning framework to study the implicit
      relationships among biological entities. A comprehensive biological ontology
      across traditional Chinese medicine (TCM) and western medicine (WM) is used to
      create a conceptual model for the biological network. Then corresponding
      biological data is integrated into a biological knowledge network as the data
      model. Based on the conceptual model and data model, a scalable OWL reasoning
      method is utilized to infer the potential associations between biological
      entities from the biological network. In our experiment, we focus on the
      association discovery between TCM and WM. The derived associations are quite
      useful for biologists to promote the development of novel drugs and TCM
      modernization. The experimental results show that the system achieves high
      efficiency, accuracy, scalability, and effectivity. 

PMID- 24877077
TI  - Potential role of A2B adenosine receptors on proliferation/migration of fetal
      endothelium derived from preeclamptic pregnancies.
AB  - To investigate the functionality of A2B adenosine receptor (A2BAR) and the nitric
      oxide (NO) and vascular endothelial growth factor (VEGF) signaling pathway in the
      endothelial cell proliferation/migration during preeclampsia, we used human
      umbilical vein endothelial cells (HUVECs) isolated from normal pregnancies (n =
      15) or pregnancies with preeclampsia (n = 15). Experiments were performed in
      presence or absence of the nonselective adenosine receptor agonist NECA, the
      A2BAR selective antagonist MRS-1754, and the nitric oxide synthase (NOS)
      inhibitor L-NAME. Results indicated that cells from preeclampsia exhibited a
      significant higher protein level of A2BAR and logEC50 for NECA-mediated
      proliferation than normotensive pregnancies. The stimulatory effect of NECA (10
      MUM, 24 h) on cell proliferation was prevented by MRS-1754 (5 nM) coincubation
      only in cells from normotensive pregnancies. Nevertheless, L-NAME (100 MUM, 24 h)
      reduced the NECA-induced cell proliferation/migration in HUVEC from normal
      pregnancy; however in preeclampsia only NECA-induced cell proliferation was
      reduced by L-NAME. Moreover, NECA increased protein nitration and abundance of
      VEGF in cells from normal pregnancy and effect prevented by MRS-1754
      coincubation. Nevertheless, in preeclampsia NECA did not affect the protein level
      of VEGF. In conclusion HUVECs from preeclampsia exhibit elevated protein level of
      A2BAR and impairment of A2BAR-mediated NO/VEGF signaling pathway.

PMID- 24877078
TI  - The effects of high-intensity versus low-intensity resistance training on leg
      extensor power and recovery of knee function after ACL-reconstruction.
AB  - OBJECTIVE: Persistent weakness is a common problem after anterior cruciate
      ligament- (ACL-) reconstruction. This study investigated the effects of high
      intensity (HRT) versus low-intensity (LRT) resistance training on leg extensor
      power and recovery of knee function after ACL-reconstruction. METHODS: 31 males
      and 19 females were randomized to HRT (n = 24) or LRT (n = 26) from week 8-20
      after ACL-reconstruction. Leg extensor power, joint laxity, and self-reported
      knee function were measured before and 7, 14, and 20 weeks after surgery. Hop
      tests were assessed before and after 20 weeks. RESULTS: Power in the injured leg
      was 90% (95% CI 86-94%) of the noninjured leg, decreasing to 64% (95% CI 60-69%)
      7 weeks after surgery. During the resistance training phase there was a
      significant group by time interaction for power (P = 0.020). Power was regained
      more with HRT compared to LRT at week 14 (84% versus 73% of noninjured leg,
      resp.; P = 0.027) and at week 20 (98% versus 83% of noninjured leg, resp.; P =
      0.006) without adverse effects on joint laxity. No other between-group
      differences were found. CONCLUSION: High-intensity resistance training during
      rehabilitation after ACL-reconstruction can improve muscle power without adverse
      effects on joint laxity.

PMID- 24877079
TI  - Cecropia pachystachya: a species with expressive in vivo topical anti
      inflammatory and in vitro antioxidant effects.
AB  - Cecropia pachystachya is a species traditionally used in Brazil to treat
      inflammation. This work aims to evaluate the topical anti-inflammatory and
      antioxidant activities of the methanolic extract of C. pachystachya (CPM) and to
      perform its chemical fingerprint by HPLC-DAD. The topical anti-inflammatory
      activity was evaluated using the mouse models of acute ear inflammation induced
      by croton oil, arachidonic acid, capsaicin, EPP, phenol, and chronic inflammation
      induced by multiple application of croton oil. The in vitro antioxidant effect of
      CPM was investigated using DPPH, reducing power, beta -carotene bleaching, and
      TBARS assays. HPLC analysis was performed to quantify the antioxidant phenolics
      orientin, isoorientin, and chlorogenic acid previously identified in CPM. CPM
      exhibited significant anti-inflammatory effect in the acute models, in some cases
      comparable to the reference drugs. Histopathological analysis showed a moderate
      chronic skin anti-inflammatory effect with decrease in vasodilation, edema, cell
      infiltration, and epidermal hyperproliferation. It also showed strong in vitro
      antioxidant activity. The contents of orientin, isoorientin, and chlorogenic acid
      were 66.5 +/- 1.8, 118.8 +/- 0.7, and 5.4 +/- 0.2 ug/mg extract, respectively.
      The topical anti-inflammatory activity of CPM could be based on its antioxidant
      properties, although other effects are probably involved, including COX
      inhibition and other mechanisms.

PMID- 24877080
TI  - Rural residents in China are at increased risk of exposure to tick-borne
      pathogens Anaplasma phagocytophilum and Ehrlichia chaffeensis.
AB  - As emerging tick born rickettsial diseases caused by A. phagocytophilum and E.
      chaffeensis, anaplasmosis and ehrlichiosis have become a serious threat to human
      and animal health throughout the world. In particular, in China, an unusual
      transmission of nosocomial cases of human granulocytic anaplasmosis occurred in
      Anhui Province in 2006 and more recent coinfection case of A. phagocytophilum and
      E. chaffeensis was documented in Shandong Province. Although the seroprevalence
      of human granulocytic anaplasmosis (former human granulocytic ehrlichiosis, HGE)
      has been documented in several studies, these data existed on local
      investigations, and also little data was reported on the seroprevalence of human
      monocytic ehrlichiosis (HME) in China. In this cross-sectional epidemiological
      study, indirect immunofluorescence antibody assay (IFA) proposed by WHO was used
      to detect A. phagocytophilum and E. chaffeensis IgG antibodies for 7,322 serum
      samples from agrarian residents from 9 provinces/cities and 819 urban residents
      from 2 provinces. Our data showed that farmers were at substantially increased
      risk of exposure. However, even among urban residents, risk was considerable.
      Seroprevalence of HGA and HME occurred in diverse regions of the country and
      tended to be the highest in young adults. Many species of ticks were confirmed
      carrying A. phagocytophilum organisms in China while several kinds of domestic
      animals including dog, goats, sheep, cattle, horse, wild rabbit, and some small
      wild rodents were proposed to be the reservoir hosts of A. phagocytophilum. The
      broad distribution of vector and hosts of the A. phagocytophilum and E.
      chaffeensis, especially the relationship between the generalized susceptibility
      of vectors and reservoirs and the severity of the disease's clinical
      manifestations and the genetic variation of Chinese HGA isolates in China, is
      urgently needed to be further investigated. 

PMID- 24877081
TI  - Mass spectrometric analysis of differentially expressed proteins in an endangered
      medicinal herb, Picrorhiza kurroa.
AB  - Picrorhiza kurroa grown in the Northwestern Himalayan region is used in various
      herbal formulations but extensive harvesting of this plant has led it to near
      extinction. The active constituents responsible for the medicinal properties of
      P. kurroa have been identified as picroside-I and picroside-II which are present
      in a particular ratio (1:1.5) in herbal formulations like Picroliv. The
      biosynthetic pathway of picrosides has been partially deciphered till date and
      needs to be elucidated completely. Review of literature revealed that no
      information is available as of today on the proteome analysis of Picrorhiza
      kurroa w.r.t. picroside-II biosynthesis. Therefore, with the aim of identifying
      proteins associated with picroside biosynthesis in Picrorhiza kurroa,
      differential protein expression was studied under picroside accumulating versus
      nonaccumulating conditions using SDS-PAGE. A total of 19 differentially expressed
      proteins were identified using MALDI-TOF/TOF MS followed by MASCOT search.
      Proteins involved in diverse functions were identified amongst which the most
      important proteins were glyceraldehyde-3-phosphate dehydrogenase, 1
      aminocyclopropane-1-carboxylate oxidase, photosystem I reaction centre subunit V,
      2-oxoglutarate ferrous-dependent oxygenase and putative cytochrome P450
      superfamily protein because of their role in picroside biosynthesis. These
      identified proteins provide an insight and a basic platform for thorough
      understanding of biosynthesis of secondary metabolites and various other
      physiological processes of P. kurroa.

PMID- 24877082
TI  - FOXP3 transcription factor: a candidate marker for susceptibility and prognosis
      in triple negative breast cancer.
AB  - Triple negative breast cancer (TNBC) is a relevant subgroup of neoplasia which
      presents negative phenotype of estrogen and progesterone receptors and has no
      overexpression of the human epidermal growth factor 2 (HER2). FOXP3 (forkhead
      transcription factor 3) is a marker of regulatory T cells (Tregs), whose
      expression may be increased in tumor cells. This study aimed to investigate a
      polymorphism (rs3761548) and the protein expression of FOXP3 for a possible
      involvement in TNBC susceptibility and prognosis. Genetic polymorphism was
      evaluated in 50 patients and in 115 controls by allele-specific PCR (polymerase
      chain reaction). Protein expression was evaluated in 38 patients by
      immunohistochemistry. It was observed a positive association for homozygous AA
      (OR = 3.78; 95% CI = 1.02-14.06) in relation to TNBC susceptibility. Most of the
      patients (83%) showed a strong staining for FOXP3 protein in the tumor cells. In
      relation to FOXP3-positive infiltrate, 47% and 58% of patients had a moderate or
      intense intratumoral and peritumoral mononuclear infiltrate cells, respectively.
      Tumor size was positively correlated to intratumoral FOXP3-positive infiltrate (P
      = 0.026). In conclusion, since FOXP3 was positively associated with TNBC
      susceptibility and prognosis, it seems to be a promising candidate for further
      investigation in larger TNBC samples. 

PMID- 24877084
TI  - Activity and safety of bevacizumab plus fotemustine for recurrent malignant
      gliomas.
AB  - BACKGROUND: No established chemotherapeutic regimen exists for the treatment of
      recurrent malignant gliomas (rMGs). Herein, we report the activity and safety
      results of the bevacizumab (B) plus fotemustine (FTM) combination for the
      treatment of rMGs. PATIENTS AND METHODS: An induction phase consisted of B 10
      mg/kg days 1, 15 plus FTM 65 mg/m(2) days 1, 8, and 15. Nonprogressive patients
      entered the maintenance phase with B 10 mg/kg plus FTM 75 mg/m(2) every 3 weeks.
      The primary endpoint was response rate; secondary endpoints included safety,
      progression free survival (PFS), and overall survival (OS). RESULTS: Twenty-six
      patients affected by recurrent MGs (50% glioblastoma) were enrolled. Eight
      partial responses (31%) were observed. Median PFS and OS were 4 (95% C.I.: 2.8
      5.1) and 6 months (95% C.I.: 4.2-7.8), respectively. Responses were significantly
      associated with both improved PFS and OS (P = 0.002 and P = 0.001, resp.).
      Treatment adverse events were mostly mild to moderate in intensity. Bevacizumab
      related adverse events included grade 3 venous thromboembolic event (8%), grade 2
      epistaxis (4%), hypertension (8%), and gastrointestinal perforation (4%).
      CONCLUSIONS: Bevacizumab plus FTM showed activity and good tolerability in
      pretreated MGs. Further investigations are needed in order to verify the benefits
      deriving from the addition of B to a cytotoxic in this clinical setting of
      patients.

PMID- 24877083
TI  - Epigenetic control of autophagy by microRNAs in ovarian cancer.
AB  - Autophagy is a lysosomal-driven catabolic process that contributes to the
      preservation of cell homeostasis through the regular elimination of cellular
      damaged, aged, and redundant molecules and organelles. Autophagy plays dual
      opposite roles in cancer: on one hand it prevents carcinogenesis; on the other
      hand it confers an advantage to cancer cells to survive under prohibitive
      conditions. Autophagy has been implicated in ovarian cancer aggressiveness and in
      ovarian cancer cell chemoresistance and dormancy. Small noncoding microRNAs
      (miRNAs) regulate gene expression at posttranscriptional level, thus playing an
      important role in many aspects of cell pathophysiology, including cancerogenesis
      and cancer progression. Certain miRNAs have recently emerged as important
      epigenetic modulators of autophagy in cancer cells. The mRNA of several autophagy
      related genes contains, in fact, the target sequence for miRNAs belonging to
      different families, with either oncosuppressive or oncogenic activities. MiRNA
      profiling studies have identified some miRNAs aberrantly expressed in ovarian
      cancer tissues that can impact autophagy. In addition, plasma and stroma cell
      derived miRNAs in tumour-bearing patients can regulate the expression of relevant
      autophagy genes in cancer cells. The present review focuses on the potential
      implications of miRNAs regulating autophagy in ovarian cancer pathogenesis and
      progression. 

PMID- 24877086
TI  - The structural modeling of the interaction between levofloxacin and the
      Mycobacterium tuberculosis gyrase catalytic site sheds light on the mechanisms of
      fluoroquinolones resistant tuberculosis in Colombian clinical isolates.
AB  - We compared the prevalence of levofloxacin (LVX) resistance with that of
      ofloxacin (OFX) and moxifloxacin (MFX) among multidrug resistant (MDR) MTB
      clinical isolates collected in Medellin, Colombia, between 2004 and 2009 and
      aimed at unraveling the underlying molecular mechanisms that explain the
      correlation between QRDR-A mutations and LVX resistance phenotype. We tested 104
      MDR isolates for their susceptibility to OFX, MFX, and LVX. Resistance to OFX was
      encountered in 10 (9.6%) of the isolates among which 8 (7.7%) were also resistant
      to LVX and 6 (5.7%) to MFX. Four isolates resistant to the 3 FQ were harboring
      the Asp94Gly substitution, whilst 2 other isolates resistant to OFX and LVX
      presented the Ala90Val mutation. No mutations were found in the QRDR-B region.
      The molecular modeling of the interaction between LVX and the DNA-DNA gyrase
      complex indicates that the loss of an acetyl group in the Asp94Gly mutation
      removes the acid base interaction with LVX necessary for the quinolone activity.
      The Ala90Val mutation that substitutes a methyl for an isopropyl group induces a
      steric modification that blocks the LVX access to the gyrase catalytic site. 

PMID- 24877085
TI  - Vitreous substitutes: the present and the future.
AB  - Vitreoretinal surgery has advanced in numerous directions during recent years.
      The removal of the vitreous body is one of the main characteristics of this
      surgical procedure. Several molecules have been tested in the past to fill the
      vitreous cavity and to mimic its functions. We here review the currently
      available vitreous substitutes, focusing on their molecular properties and
      functions, together with their adverse effects. Afterwards we describe the
      characteristics of the ideal vitreous substitute. The challenges facing every
      ophthalmology researcher are to reach a long-term intraocular permanence of
      vitreous substitute with total inertness of the molecule injected and the control
      of inflammatory reactions. We report new polymers with gelification
      characteristics and smart hydrogels representing the future of vitreoretinal
      surgery. Finally, we describe the current studies on vitreous regeneration and
      cell cultures to create new intraocular gels with optimal biocompatibility and
      rheological properties. 

PMID- 24877087
TI  - Assessment of DNA damage and telomerase activity in exfoliated urinary cells as
      sensitive and noninvasive biomarkers for early diagnosis of bladder cancer in ex
      workers of a rubber tyres industry.
AB  - The aim of the present study was to identify sensitive and noninvasive biomarkers
      of early carcinogenic effect at target organ to use in biomonitoring studies of
      workers at risk for previous occupational exposure to potential carcinogens.
      Standard urine cytology (Papanicolaou staining test), comet assay, and
      quantitative telomerase repeat amplification protocol (TRAP) assay were performed
      in 159 ex-rubber workers employed in tyres production and 97 unexposed subjects.
      In TRAP positive cases, a second level analysis using FISH (Urovysion) was done.
      Cystoscopy results were available for 11 individuals whose 6 FISH/TRAP/comet
      positive showed in 3 cases a dysplastic condition confirmed by biopsy, 1 comet
      positive resulted in infiltrating UBC to the biopsy and with hyperplasia and
      slight dysplasia to the urinary cytology, 1 comet positive resulted in papillary
      superficial UBC to the biopsy, 1 FISH/TRAP positive showed a normal condition,
      and 2 TRAP positive showed in one case a phlogosis condition. The results
      evidenced good concordance of TRAP, comet, and FISH assays as early biomarkers of
      procarcinogenic effect confirmed by the dysplastic condition and UBC found by
      cystoscopy-biopsy analysis. The analysis of these markers in urine cells could be
      potentially more accurate than conventional cytology in monitoring workers
      exposed to mixture of bladder potential carcinogens. 

PMID- 24877088
TI  - Complete cell killing by applying high hydrostatic pressure for acellular
      vascular graft preparation.
AB  - Pressure treatment has been developed in tissue engineering application. Although
      the tissue scaffold prepared by a ultrahydrostatic pressure treatment has been
      reported, an excessive pressure has a potential to disrupt a structure of
      extracellular matrix through protein denaturation. It is important to understand
      the suitable low-pressure condition and mechanisms for cell killing. In this
      study, cellular morphology, mitochondria activity, and membrane permeability of
      mammalian cells with various pressure treatments were investigated with in vitro
      models. When the cells were treated with a pressure of 100 MPa for 10 min, cell
      morphology and adherence were the same as an untreated cells. Dehydrogenase
      activity in mitochondria was almost the same as untreated cells. On the other
      hand, when the cells were treated with the pressure of more than 200 MPa, the
      cells did not adhere, and the dehydrogenase activity was completely suppressed.
      However, green fluorescence was observed in the live/dead staining images, and
      the cells were completely stained as red after above 500 MPa. That is, membrane
      permeability was disturbed with the pressure treatment of above 500 MPa. These
      results indicated that the pressure of 200 MPa for 10 min was enough to induce
      cell killing through inactivation of mitochondria activity.

PMID- 24877089
TI  - Design and reliability of a novel heel rise test measuring device for
      plantarflexion endurance.
AB  - BACKGROUND: Plantarflexion results from the combined action of the soleus and
      gastrocnemius muscles in the calf. The heel rise test is commonly used to test
      calf muscle endurance, function, and performance by a wide variety of
      professionals; however, no uniform description of the test is available. This
      paper aims to document the construction and reliability of a novel heel rise test
      device and measurement protocol that is suitable for the needs of most
      individuals. METHODS: This device was constructed from compact and lightweight
      materials and is fully adjustable, enabling the testing of a wide variety of
      individuals. It is easy to assemble and disassemble, ensuring that it is portable
      for use in different settings. FINDINGS: We tested reliability on 40
      participants, finding excellent interrater reliability (ICC2,1 0.97, 95% CI: 0.94
      to 0.98). Limits of agreement were less than two repetitions in 90% of cases and
      the Bland-Altman plot showed no bias. INTERPRETATION: We have designed a novel,
      standardized, simple, and reliable device and measurement protocol for the heel
      rise test which can be used by researchers and clinicians in a variety of
      settings.

PMID- 24877090
TI  - Nerve injury-induced c-Jun activation in Schwann cells is JNK independent.
AB  - We investigated (a) if activation of the mitogen activated protein kinase (MAPK)
      pathway was linked to the stress activated protein kinase (SAPK) pathway and (b)
      if JNK was required for activation of c-Jun in Schwann cells of rat sciatic nerve
      following injury. To this aim, ERK1/2 and the transcription factors c-Jun and ATF
      3 were studied by immunohistochemistry in segments of transected nerves. We
      utilized pharmacological inhibitors of both signal transduction pathways in vitro
      to determine the effects on downstream signalling events, such as c-Jun
      activation, and on Schwann cell survival and proliferation. A transection induces
      c-Jun and ATF-3 transcription in Schwann cells. These events are followed by
      Schwann cell activation of c-Jun in the injured nerve. The MAPK inhibitor U0126
      blocked ERK1/2 activation and reduced Schwann cell proliferation as well as
      induction of c-Jun transcription. The JNK inhibitor SP600125 reduced Schwann cell
      proliferation, but did not affect the expression of ERK1/2 or injury-induced
      increases in c-Jun or ATF-3 levels. Importantly, nerve injury induces Schwann
      cell activation of c-Jun by phosphorylation, which, in contrast to in sensory
      neurons, is JNK independent. MAP kinases, other than JNK, can potentially
      activate c-Jun in Schwann cells following injury; information that is crucial to
      create new nerve reconstruction strategies. 

PMID- 24877091
TI  - CCAAT/enhancer-binding protein alpha is a crucial regulator of human fat mass and
      obesity associated gene transcription and expression.
AB  - Several susceptibility loci have been reported associated with obesity and T2DM
      in GWAS. Fat mass and obesity associated gene (FTO) is the first gene associated
      with body mass index (BMI) and risk for diabetes in diverse patient populations.
      FTO is highly expressed in the brain and pancreas, and is involved in regulating
      dietary intake and energy expenditure. While much is known about the epigenetic
      mutations contributing to obesity and T2DM, less is certain with the expression
      regulation of FTO gene. In this study, a highly conserved canonical C/EBP alpha
      binding site was located around position -45~-54 bp relative to the human FTO
      gene transcriptional start site. Site-directed mutagenesis of the putative C/EBP
      alpha binding sites decreased FTO promoter activity. Overexpression and RNAi
      studies also indicated that C/EBP alpha was required for the expression of FTO.
      Chromatin immunoprecipitation (ChIP) experiment was carried out and the result
      shows direct binding of C/EBP alpha to the putative binding regions in the FTO
      promoter. Collectively, our data suggest that C/EBP alpha may act as a positive
      regulator binding to FTO promoter and consequently, activates the gene
      transcription.

PMID- 24877093
TI  - The Kampo medicine Rokumigan possesses antibiofilm, anti-inflammatory, and wound
      healing properties.
AB  - Periodontal diseases, which are inflammatory diseases of bacterial origin
      affecting the tooth-supporting tissues, are characterized by inflammation and
      destruction of gingival connective tissue and alveolar bone, and may lead to
      tooth loss. The aim of the study was to investigate Rokumigan, a Kampo Japanese
      traditional medicine made of six different plants, for its capacity to prevent
      biofilm formation by Fusobacterium nucleatum, to inhibit interleukin-6 (IL-6) and
      interleukin-8 (IL-8) secretion by mucosal cells, and to promote wound healing in
      a fibroblast model. Using a microplate colorimetric assay, Rokumigan prevented
      biofilm formation by F. nucleatum, while it had no effect on bacterial growth.
      Rokumigan inhibited IL-6 secretion in both epithelial cells and fibroblasts
      stimulated with lipopolysaccharide. However, it caused no significant inhibition
      of IL-8 secretion by both cell types. Rokumigan significantly increased
      proliferation and migration of gingival fibroblasts in a wound healing assay. In
      conclusion, the Kampo formulation Rokumigan, through suppression of biofilm
      formation by F. nucleatum, inhibition of IL-6 secretion by gingival epithelial
      cells and fibroblasts, and promotion of wound healing in a fibroblast model, may
      have potential application for periodontal diseases. 

PMID- 24877094
TI  - Distensibility and strength of the pelvic floor muscles of women in the third
      trimester of pregnancy.
AB  - OBJECTIVE: The objective of this study was to compare the role of the pelvic
      floor muscles between nulliparous and multiparous women in the third trimester of
      pregnancy, by analyzing the relationship between electrical activity (surface
      electromyography-EMG), vaginal palpation (modified Oxford scale), and perineal
      distensibility (Epi-no). METHODS: This was an observational cross-sectional study
      on a sample of 60 healthy pregnant women with no cervical dilation, single fetus,
      gestational age between 35 and 40 weeks, and maternal age ranging from 15 to 40
      years. The methods used were bidigital palpation (modified Oxford scale, graded 0
      5), surface EMG (electrical activity during maximal voluntary contraction), and
      perineal distensibility (Epi-no device). The Pearson correlation coefficient (r)
      was used to analyze the Epi-no values and the surface EMG findings. The Kruskal
      Wallis test was used to compare the median values from surface EMG and Epi-no,
      using the modified Oxford scale scores. RESULTS: Among the 60 patients included
      in this study, 30 were nulliparous and 30 multiparous. The average maternal age
      and gestational age were 26.06 (+/- 5.58) and 36.56 (+/- 1.23), respectively. It
      was observed that nulliparous women had both higher perineal muscle strength
      (2.53 +/- 0.57 versus 2.06 +/- 0.64; P = 0.005) and higher electrical activity
      (45.35 +/- 12.24 MUV versus 35.79 +/- 11.66 MUV; P = 0.003), while among the
      multiparous women, distensibility was higher (19.39 +/- 1.92 versus 18.05 +/-
      2.14; P = 0.013). We observed that there was no correlation between perineal
      distensibility and electrical activity during maximal voluntary contraction (r = 
      0.193; P = 0.140). However, we found a positive relationship between vaginal
      palpation and surface electromyography (P = 0.008), but none between Epi-no
      values (P = 0.785). CONCLUSION: The electrical activity and muscle strength of
      the pelvic floor muscles of the multiparous women were damaged, in relation to
      the nulliparous women, while the perineal distensibility was lower in the latter
      group. There was a positive relationship between surface EMG and the modified
      Oxford scale.

PMID- 24877092
TI  - The role of physical exercise in inflammatory bowel disease.
AB  - We reviewed and analyzed the relationship between physical exercise and
      inflammatory bowel disease (IBD) which covers a group of chronic, relapsing, and
      remitting intestinal disorders including Crohn's disease (CD) and ulcerative
      colitis. The etiology of IBD likely involves a combination of genetic
      predisposition and environmental risk factors. Physical training has been
      suggested to be protective against the onset of IBD, but there are
      inconsistencies in the findings of the published literature. Hypertrophy of the
      mesenteric white adipose tissue (mWAT) is recognized as a characteristic feature
      of CD, but its importance for the perpetuation of onset of this intestinal
      disease is unknown. Adipocytes synthesize proinflammatory and anti-inflammatory
      cytokines. Hypertrophy of mWAT could play a role as a barrier to the inflammatory
      process, but recent data suggest that deregulation of adipokine secretion is
      involved in the pathogenesis of CD. Adipocytokines and macrophage mediators
      perpetuate the intestinal inflammatory process, leading to mucosal ulcerations
      along the mesenteric border, a typical feature of CD. Contracting skeletal
      muscles release biologically active myokines, known to exert the direct anti
      inflammatory effects, and inhibit the release of proinflammatory mediators from
      visceral fat. Further research is required to confirm these observations and
      establish exercise regimes for IBD patients. 

PMID- 24877095
TI  - Psychometric properties of questionnaires on functional health status in
      oropharyngeal dysphagia: a systematic literature review.
AB  - INTRODUCTION: Questionnaires on Functional Health Status (FHS) are part of the
      assessment of oropharyngeal dysphagia. OBJECTIVE: To conduct a systematic review
      of the literature on the psychometric properties of English-language FHS
      questionnaires in adults with oropharyngeal dysphagia. METHODS: A systematic
      search was performed using the electronic databases Pubmed and Embase. The
      psychometric properties of the questionnaires were determined based on the COSMIN
      taxonomy of measurement properties and definitions for health-related patient
      reported outcomes and the COSMIN checklist using preset psychometric criteria.
      RESULTS: Three questionnaires were included: the Eating Assessment Tool (EAT-10),
      the Swallowing Outcome after Laryngectomy (SOAL), and the Self-report Symptom
      Inventory. The Sydney Swallow Questionnaire (SSQ) proved to be identical to the
      Modified Self-report Symptom Inventory. All FHS questionnaires obtained poor
      overall methodological quality scores for most measurement properties.
      CONCLUSIONS: The retrieved FHS questionnaires need psychometric reevaluation; if
      the overall methodological quality shows satisfactory improvement on most
      measurement properties, the use of the questionnaires in daily clinic and
      research can be justified. However, in case of insufficient validity and/or
      reliability scores, new FHS questionnaires need to be developed using and
      reporting on preestablished psychometric criteria as recommended in literature.

PMID- 24877096
TI  - Elastase and cathepsin G from primed leukocytes cleave vascular endothelial
      cadherin in hemodialysis patients.
AB  - AIMS: To test the hypothesis that primed PMNLs in blood of chronic kidney disease
      patients release the active form of elastase and cathepsin G causing degradation
      of vital proteins and promote tissue damage. METHODS: RT-PCR, immunocytochemical
      staining, immunoblotting, and FACS analyses were used to study these enzymes in
      hemodialysis patients (HD) versus healthy normal controls (NC). Using PMNLs and
      endothelial cells cocultivation system we measure the effect of HD PMNLs on the
      endothelial VE-cadherin, an essential protein for maintaining endothelial
      integrity. RESULTS: Levels of elastase and cathepsin G were reduced in PMNLs of
      HD patients, while mRNA enzymes levels were not different. Elevated levels of the
      active form of these enzymes were found in blood of HD patients compared to NC.HD
      plasma had higher levels of soluble VE-cadherin present in three molecular forms:
      whole 140 kDa molecule and two fragments of 100 and 40 kDa. Cocultivation studies
      showed that primed PMNLs cleave the endothelial cadherin, resulting in a 100 kDa
      fragment. CONCLUSIONS: Elastase and cathepsin G are elevated in the plasma of HD
      patients, originating from primed PMNLs. In these patients, chronic elevation of
      these enzymes contributes to cleavage of VE-cadherin and possible disruption of
      endothelial integrity.

PMID- 24877097
TI  - Long-term outcome after laparoscopic bowel resections for deep infiltrating
      endometriosis: a single-center experience after 900 cases.
AB  - BACKGROUND: Laparoscopic bowel resections for endometriosis are safe and
      effective but only short-term follow-up has been evaluated. In the present study
      long-term outcome in terms of intestinal and urinary function, fertility, chronic
      pain, and recurrence was assessed. MATERIALS AND METHODS: From January 2002 to
      December 2010 nine hundred patients underwent laparoscopic bowel resection for
      endometriosis, and on 774 (86%) a questionnaire was administered. Patients were
      divided into 3 groups on the strength of the operation date. Postoperative
      diarrhea, constipation, rectal bleeding, tenesmus, dyschezia, dysuria,
      dyspareunia, fertility, and recurrence of disease were assessed. RESULTS: The
      median follow-up was 54 months (range 1-120). All the evaluated symptoms
      significantly improved over time, with P = 0.0001 for dyspareunia, constipation,
      and pelvic pain and P = 0.004 for diarrhea. Nonsignificant improvement was
      reported for dysuria and rectal bleeding (with P = 0.452 and P = 0.097, resp.).
      CONCLUSIONS: The present results confirm that bowel resections for endometriosis
      are correlated with an acceptable complication rate even at long-term follow-up
      and that symptoms significantly improve over time, except for rectal bleeding and
      dysuria, the latter associated with a neurological damage.

PMID- 24877099
TI  - A survey of Italian physicians' opinion about stem cells research: what doctors
      prefer and what the law requires.
AB  - To evaluate the Italian physicians' knowledge/information level about the
      therapeutic potential of stem cells, the research choice between embryonic and
      cordonal stem cells, and the preference between autologous and heterologous
      storage of cordonal stem cells, we performed a national survey. The questionnaire
      -distributed to 3361 physicians--involved physicians of different religious
      orientations and of different medical specialities. Most of the physicians
      involved (67%) were Catholics, and the majority were gynaecologists and
      paediatricians (43%) who are mainly in charge to inform future mothers about the
      possibility of cordonal stem cells conservation. The majority of the physicians
      interviewed do not have specific knowledge about stem cells (59%), most of them
      having only generic information (92%). The largest part of physicians prefer to
      use umbilical cord blood cells rather than embryonic stem cells. Nevertheless, a
      large percentage of physicians were in favour of embryo research, especially when
      embryos are supernumerary (44% versus 34%). Eighty-seven % of the physicians
      interviewed proved to have a general knowledge about stem cells and believe in
      their therapeutic potential. They prefer research on cordonal stem cells rather
      than on embryo stem cells. Although they are in favour of heterologous stem cells
      donation, they still prefer cryopreservation for personal use.

PMID- 24877098
TI  - Cystitis: from urothelial cell biology to clinical applications.
AB  - Cystitis is a urinary bladder disease with many causes and symptoms. The severity
      of cystitis ranges from mild lower abdominal discomfort to life-threatening
      haemorrhagic cystitis. The course of disease is often chronic or recurrent.
      Although cystitis represents huge economical and medical burden throughout the
      world and in many cases treatments are ineffective, the mechanisms of its origin
      and development as well as measures for effective treatment are still poorly
      understood. However, many studies have demonstrated that urothelial dysfunction
      plays a crucial role. In the present review we first discuss fundamental issues
      of urothelial cell biology, which is the core for comprehension of cystitis. Then
      we focus on many forms of cystitis, its current treatments, and advances in its
      research. Additionally we review haemorrhagic cystitis with one of the leading
      causative agents being chemotherapeutic drug cyclophosphamide and summarise its
      management strategies. At the end we describe an excellent and widely used animal
      model of cyclophosphamide induced cystitis, which gives researches the
      opportunity to get a better insight into the mechanisms involved and possibility
      to develop new therapy approaches. 

PMID- 24877101
TI  - Downtime after critical incidents in emergency medical technicians/paramedics.
AB  - Effective workplace-based interventions after critical incidents (CIs) are needed
      for emergency medical technicians (EMT)/paramedics. The evidence for a period out
      of service post-CI (downtime) is sparse; however it may prevent posttraumatic
      stress disorder (PTSD) and burnout symptoms. We examined the hypothesis that
      downtime post-CI is associated with fewer symptoms of four long-term emotional
      sequelae in EMT/paramedics: depression, PTSD, burnout, and stress-related
      emotional symptoms (accepted cut-offs defined high scores). Two hundred and one
      paramedics completed questionnaires concerning an index CI including downtime
      experience, acute distress, and current emotional symptoms. Nearly 75% received
      downtime; 59% found it helpful; 84% spent it with peers. Downtime was associated
      only with lower depression symptoms, not with other outcomes. The optimal period
      for downtime was between <30 minutes and end of shift, with >1 day being less
      effective. Planned testing of mediation of the association between downtime and
      depression by either calming acute post-CI distress or feeling helped by others
      was not performed because post-CI distress was not associated with downtime and
      perceived helpfulness was not associated with depression. These results suggest
      that outcomes of CIs follow different pathways and may require different
      interventions. A brief downtime is a relatively simple and effective strategy in
      preventing later depression symptoms. 

PMID- 24877102
TI  - Novel molecular beacon probe-based real-time RT-PCR assay for diagnosis of
      Crimean-Congo hemorrhagic fever encountered in India.
AB  - Crimean-Congo hemorrhagic fever (CCHF) is an emerging zoonotic disease in India
      and requires immediate detection of infection both for preventing further
      transmission and for controlling the infection. The present study describes
      development, optimization, and evaluation of a novel molecular beacon-based real
      time RT-PCR assay for rapid, sensitive, and specific diagnosis of Crimean-Congo
      hemorrhagic fever virus (CCHFV). The developed assay was found to be a better
      alternative to the reported TaqMan assay for routine diagnosis of CCHF. 

PMID- 24877100
TI  - Investigating the synergistic interaction of diabetes, tobacco smoking, alcohol
      consumption, and hypercholesterolemia on the risk of pancreatic cancer: a case
      control study in Italy.
AB  - The aims of the present research are to investigate the possible predictors of
      pancreatic cancer, in particular smoking status, alcohol consumption,
      hypercholesterolemia, and diabetes mellitus, in patients with histologically
      confirmed pancreatic carcinoma and to examine the synergism between risk factors.
      A case-control study (80 patients and 392 controls) was conducted at the Teaching
      Hospital "Agostino Gemelli" in Rome. A conditional logistic regression was used
      for the statistical analysis and results were presented as odds ratio (OR) and
      95% confidence intervals (95% CI). We also investigated the possible interactions
      between risk factors and calculated the synergism index (SI). The multivariate
      analysis revealed that hypercholesterolemia and alcohol consumption resulted in
      important risk factors for pancreatic cancer even after the adjustment for all
      variables (OR: 5.05, 95% CI: 2.94-8.66; OR: 2.25, 95% CI: 1.30-3.89, resp.).
      Interestingly, important synergistic interactions between risk factors were
      found, especially between ever smoking status and alcohol consumptions (SI =
      17.61) as well as alcohol consumption and diabetes (SI = 17.77). In conclusion,
      the study confirms that hypercholesterolemia and alcohol consumption represent
      significant and independent risk factors for pancreatic cancer. Moreover, there
      is evidence of synergistic interaction between diabetes and lifestyle factors
      (drinking alcohol and eating fatty foods). 

PMID- 24877103
TI  - Possible association of IL-4 VNTR polymorphism with susceptibility to
      preeclampsia.
AB  - Preeclampsia (PE) is a pregnancy-specific disorder that results in maternal
      mortality and morbidity. Growing evidence indicated that cytokines are involved
      in the pathogenesis of PE and interleukin-4 VNTR polymorphism could be implicated
      in altering the PE risk. The aim of this study was to evaluate the possible
      association between IL-4 VNTR polymorphism and susceptibility to PE in Iranian
      population for the first time. Genetic polymorphism was evaluated in 192 PE and
      186 healthy control women by polymerase chain reaction method. We found that the
      VNTR polymorphism of IL-4 gene has significantly increased the risk of
      preeclampsia (RP2/RP1 versus RP1/RP1, OR, 2.8 [95% CI, 1.7 to 8.8]; P = 0.0001
      and RP2/RP2 versus RP1/RP1; P = 0.002). The results showed that carriage of IL-4
      VNTR RP2 allele has positive association with preeclampsia susceptibility. 

PMID- 24877104
TI  - Differential hypermethylation of death-associated protein kinase promoter in
      central neurocytoma and oligodendroglioma.
AB  - BACKGROUND: Central neurocytoma and oligodendroglioma are rare tumors of the
      central nervous system. However, diagnosis between these two types of tumors is
      challenging due to their many cytological and histological similarities. Death
      associated protein kinase (DAPK) is a calcium/calmodulin-regulated
      serine/threonine protein kinase involved in many apoptosis pathways, and
      repressed expression of DAPK by promoter hypermethylation has been found in a
      variety of human cancers. The purpose of this study was to assess DAPK protein
      expression and promoter hypermethylation in central neurocytoma and
      oligodendroglioma. METHOD: Central neurocytoma and oligodendroglioma samples were
      obtained from age- and sex-matched patients. DAPK protein expression was
      performed using immunohistochemical assays in formalin-fixed, paraffin-embedded
      sections. DAPK promoter hypermethylation was carried out using bisulfite-modified
      genomic DNA in methylation-specific PCR followed by separation in agarose gels.
      FINDINGS: A statistically significant difference (P = 0.021) in DAPK promoter
      hypermethylation between central neurocytoma (76.9%) and oligodendroglioma (20%)
      was observed. High levels of DAPK protein expression were generally found in
      oligodendroglioma (90%), compared with 38.5% in central neurocytoma (P = 0.054;
      not statistically significant). There was an inverse correlation between DAPK
      protein expression and DAPK promoter hypermethylation in the cohort of 23
      patients (P = 0.002). CONCLUSIONS: The results show that DAPK promoter
      hypermethylation and repressed expression of DAPK protein were more common in
      central neurocytoma than in oligodendroglioma. Thus, DAPK promoter
      hypermethylation could be useful for differential diagnosis between these two
      types of tumors, whereas DAPK protein expression might be less predictive. The
      role of DAPK promoter hypermethylation in the pathogenesis of central neurocytoma
      warrants further study.

PMID- 24877105
TI  - Relationships of alpha-SMA-positive fibroblasts and SDF-1-positive tumor cells
      with neoangiogenesis in nasopharyngeal carcinoma.
AB  - Nasopharyngeal carcinoma (NPC) is one of the most prevalent malignant tumors with
      poor prognosis in Southern China and Southeast Asia. Angiogenesis-related
      molecules can be promising therapeutic targets in NPC. To investigate the
      relationships of cancer-associated fibroblasts (CAFs) and chemokine-related
      molecules with neoangiogenesis, we compared immunohistochemical analyses of alpha
      smooth-muscle actin (alpha-SMA), stroma-derived factor-1 (SDF-1), and its
      receptor CXCR4 in primary NPC specimens and chronic nasopharyngitis tissues. In
      addition, we examined the expression of vascular endothelial growth factor (VEGF
      A), and CD133- and VEGF- receptor-2 (VEGFR-2) double positive cells, as
      endothelial progenitor cells (EPCs). We also assessed CD34-positive microvessels.
      Significantly higher expression of alpha -SMA was observed in fibroblasts in NPC
      stroma. The immunoreactive intensities of SDF-1 and CXCR4 were significantly
      higher in NPC cells. CXCR4-positive cells and CD133/VEGFR-2- double positive
      cells were observed in the stroma surrounding cancer nests, and VEGF was detected
      in both cancer and stromal cells. Microvessel density was significantly higher in
      the stroma of NPC tissues compared to chronic nasopharyngitis tissues. Our data
      suggest that CAFs and NPC tumor cells may enhance neoangiogenesis in a VEGF- and
      SDF-1-dependent manner by recruiting EPCs from the bone marrow into tumor stroma.

PMID- 24877106
TI  - Role of dried fruits of Carissa carandas as anti-inflammatory agents and the
      analysis of phytochemical constituents by GC-MS.
AB  - Inflammation plays an important role in various diseases with high prevalence
      within populations such as rheumatoid arthritis, ulcer, atherosclerosis, and
      asthma. Many drugs are available in the market for inflammatory diseases. They
      exhibit several unwanted side effects to humans. Therefore, alternative
      treatments with safer compounds are needed. Carissa carandas plant is used in
      traditional medicinal system for its various diseases curing property. In the
      present study, we examined the anti-inflammatory effects of dried fruit methanol
      extract on carrageenan-induced hind paw edema in rats. C. carandas was defatted
      with petroleum ether, followed by methanol extraction. The methanol extracts of
      the dried fruits of Carissa carandas were given orally to the experimental rats
      caused significant activity (P <= 0.05) when compared with the control group. The
      maximum inhibition of paw edema was found to be in Group V, that is, 76.12% with
      inhibition of paw volume in a dose-dependent manner. The anti-inflammatory
      activity of the methanol extract of the dried fruits shows that the presence of
      potential constituents present in this extract may provide assistance in the drug
      discovery process. The phytochemical compounds of the extract were screened by GC
      MS analysis and it was found that 11 compounds are present in methanol extract of
      dried fruits of Carissa carandas. 

PMID- 24877107
TI  - Watermelon (Citrullus lanatus (Thunb.) Matsum. and Nakai) juice modulates
      oxidative damage induced by low dose X-ray in mice.
AB  - Watermelon is a natural product that contains high level of antioxidants and may
      prevent oxidative damage in tissues due to free radical generation following an
      exposure to ionizing radiation. The present study aimed to investigate the
      radioprotective effects of watermelon (Citrullus lanatus (Thunb.) Matsum. and
      Nakai) juice against oxidative damage induced by low dose X-ray exposure in mice.
      Twelve adult male ICR mice were randomly divided into two groups consisting of
      radiation (Rx) and supplementation (Tx) groups. Rx received filtered tap water,
      while Tx was supplemented with 50% (v/v) watermelon juice for 28 days ad libitum
      prior to total body irradiation by 100 MUGy X-ray on day 29. Brain, lung, and
      liver tissues were assessed for the levels of malondialdehyde (MDA),
      apurinic/apyrimidinic (AP) sites, glutathione (GSH), and superoxide dismutase
      (SOD) inhibition activities. Results showed significant reduction of MDA levels
      and AP sites formation of Tx compared to Rx (P < 0.05). Mice supplemented with
      50% watermelon juice restore the intracellular antioxidant activities by
      significantly increased SOD inhibition activities and GSH levels compared to Rx.
      These findings may postulate that supplementation of 50% watermelon (Citrullus
      lanatus (Thunb.) Matsum. and Nakai) juice could modulate oxidative damage induced
      by low dose X-ray exposure.

PMID- 24877109
TI  - Significance of chromosome 9p status in renal cell carcinoma: a systematic review
      and quality of the reported studies.
AB  - Defining the prognosis of renal cell carcinoma (RCC) using genetic tests is an
      evolving area. The prognostic significance of 9p status in RCC, although
      described in the literature, remains underutilised in clinical practice. The
      study explored the causes of this translational gap. A systematic review on the
      significance of 9p status in RCC was performed to assess its clinical
      applicability and impact on clinical decision-making. Medline, Embase, and other
      electronic searches were made for studies reporting on 9p status in RCC. We
      collected data on: genetic techniques, pathological parameters, clinical
      outcomes, and completeness of follow-up assessment. Eleven studies reporting on
      1,431 patients using different genetic techniques were included. The most
      commonly used genetic technique for the assessment of 9p status in RCC was
      fluorescence in situ hybridization. Combined genomic hybridisation (CGH),
      microsatellite analysis, karyotyping, and sequencing were other reported
      techniques. Various thresholds and cut-off values were used for the diagnosis of
      9p deletion in different studies. Standardization, interobserver agreement, and
      consensus on the interpretation of test remained poor. The studies lacked
      validation and had high risk of bias and poor clinical applicability as assessed
      by two independent reviewers using a modified quality assessment tool. Further
      protocol driven studies with standardised methodology including use of
      appropriate positive and negative controls, assessment of interobserver
      variations, and evidenced based follow-up protocols are needed to clarify the
      role of 9p status in predicting oncological outcomes in renal cell cancer. 

PMID- 24877108
TI  - New tools for embryo selection: comprehensive chromosome screening by array
      comparative genomic hybridization.
AB  - The objective of this study was to evaluate the usefulness of comprehensive
      chromosome screening (CCS) using array comparative genomic hybridization (aCGH).
      The study included 1420 CCS cycles for recurrent miscarriage (n = 203);
      repetitive implantation failure (n = 188); severe male factor (n = 116); previous
      trisomic pregnancy (n = 33); and advanced maternal age (n = 880). CCS was
      performed in cycles with fresh oocytes and embryos (n = 774); mixed cycles with
      fresh and vitrified oocytes (n = 320); mixed cycles with fresh and vitrified day
      2 embryos (n = 235); and mixed cycles with fresh and vitrified day-3 embryos (n =
      91). Day-3 embryo biopsy was performed and analyzed by aCGH followed by day-5
      embryo transfer. Consistent implantation (range: 40.5-54.2%) and pregnancy rates
      per transfer (range: 46.0-62.9%) were obtained for all the indications and
      independently of the origin of the oocytes or embryos. However, a lower delivery
      rate per cycle was achieved in women aged over 40 years (18.1%) due to the higher
      percentage of aneuploid embryos (85.3%) and lower number of cycles with at least
      one euploid embryo available per transfer (40.3%). We concluded that aneuploidy
      is one of the major factors which affect embryo implantation. 

PMID- 24877110
TI  - Virulence factors associated with pediatric shigellosis in Brazilian Amazon.
AB  - Shigellosis is a global human health problem and the incidence is highest among
      children. In the present work, main Shigella virulence genes was examined by PCR
      and compared to symptoms of pediatric shigellosis. Thirty Shigella isolates were
      identified from an etiologic study at which 1,339 children ranging 0-10 years old
      were enrolled. S. flexneri was the most frequent species reaching 60.0% of
      isolates, 22.2% were S. sonnei, and 6.6% were both S. dysenteriae and S. boydii.
      All Shigella infected children had diarrhea, but not all were accompanied by
      others symptoms of bacillary dysentery. Among major virulence genes, the PCR
      typing revealed ipaBCD was present in all isolates, followed by IpaH7.8, set-1A,
      set-1B, sen/ospD3, virF, and invE. The pathogenic potential of the ShET-1B
      subunit was observed in relation to dehydration (P < 0.001) and ShET-2 related to
      the intestinal injury (P = 0.033) evidenced by the presence of bloody diarrhea.
      Our results show associations among symptoms of shigellosis and virulence genes
      of clinical isolates of Shigella spp. 

PMID- 24877111
TI  - IDH mutations: genotype-phenotype correlation and prognostic impact.
AB  - IDH1/2 mutation is the most frequent genomic alteration found in gliomas,
      affecting 40% of these tumors and is one of the earliest alterations occurring in
      gliomagenesis. We investigated a series of 1305 gliomas and showed that IDH
      mutation is almost constant in 1p19q codeleted tumors. We found that the
      distribution of IDH1(R132H) , IDH1(nonR132H) , and IDH2 mutations differed
      between astrocytic, mixed, and oligodendroglial tumors, with an
      overrepresentation of IDH2 mutations in oligodendroglial phenotype and an
      overrepresentation of IDH1(nonR132H) in astrocytic tumors. We stratified grade II
      and grade III gliomas according to the codeletion of 1p19q and IDH mutation to
      define three distinct prognostic subgroups: 1p19q and IDH mutated, IDH mutated-
      which contains mostly TP53 mutated tumors, and none of these alterations. We
      confirmed that IDH mutation with a hazard ratio = 0.358 is an independent
      prognostic factor of good outcome. These data refine current knowledge on IDH
      mutation prognostic impact and genotype-phenotype associations.

PMID- 24877112
TI  - Evaluation of anticonvulsant, sedative, anxiolytic, and phytochemical profile of
      the methanol extract from the aerial parts of Swertia corymbosa (Griseb.) wight
      ex C.B. Clarke.
AB  - The objective of the present study was to evaluate the anxiolytic,
      antidepressant, and anticonvulsant activity of the methanolic extract of Swertia
      corymbosa (SCMeOH). After acute toxicity test, oral treatment with SCMeOH at
      doses of 125, 250, and 500 mg/kg behavioral models of open field, elevated-plus
      maze, actophotometer, rotarod, pentylenetetrazole, isoniazid, and maximal
      electroshock induced seizure models were utilized. In open field test, SCMeOH
      (125, 250, and 500 mg/kg) (P < 0.01, P < 0.001) increased the number of rearings.
      However, the number of central motor and ambulation (P < 0.01, P < 0.001) were
      reduced. Likewise, the number of entries and the time spent in open arm were
      increased while the number of locomotion was decreased (P < 0.001) in elevated
      plus-maze and actophotometer test, respectively. SCMeOH (125-500 mg/kg) protected
      the mice against the pentylenetetrazole and isoniazid induced convulsions; it
      causes significant (P < 0.01 and P < 0.001) dose dependent increase in latency of
      convulsion. Treatment with SCMeOH reduced the duration of the tonic hind limb
      extension induced by electroshock. Two major compounds such as gentiopicroside
      and swertianin were analyzed by HPLC system.

PMID- 24877113
TI  - BMPs as therapeutic targets and biomarkers in astrocytic glioma.
AB  - Astrocytic glioma is the most common brain tumor. The glioma initiating cell
      (GIC) fraction of the tumor is considered as highly chemoresistant, suggesting
      that GICs are responsible for glioma relapse. A potential treatment for glioma is
      to induce differentiation of GICs to a more benign and/or druggable cell type.
      Given BMPs are among the most potent inducers of GIC differentiation, they have
      been considered as noncytotoxic therapeutic compounds that may be of use to
      prevent growth and recurrence of glioma. We herein summarize advances made in the
      understanding of the role of BMP signaling in astrocytic glioma, with a
      particular emphasis on the effects exerted on GICs. We discuss the prognostic
      value of BMP signaling components and the implications of BMPs in the
      differentiation of GICs and in their sensitization to alkylating drugs and
      oncolytic therapy/chemotherapy. This mechanistic insight may provide new
      opportunities for therapeutic intervention of brain cancer. 

PMID- 24877114
TI  - Serum C-reactive protein and procalcitonin kinetics in patients undergoing
      elective total hip arthroplasty.
AB  - BACKGROUND: The sensitivity and the specificity of different methods to detect
      periprosthetic infection have been questioned. The current study aimed to
      investigate the kinetics of C-reactive protein (CRP) and procalcitonin (PCT) in
      patients undergoing uncomplicated elective total hip arthroplasty (THA), to
      provide a better interpretation of their levels in noninfectious inflammatory
      reaction. METHODS: A total of 51 patients were included. Serum CRP and PCT
      concentrations were obtained before surgery, on the 1st, 3rd, and 7th
      postoperative days and after discharge on the 14th and 30th days and at 2 years.
      RESULTS: Both markers were confirmed to increase after surgery. The serum CRP
      showed a marked increase on the 3rd postoperative day while the peak of serum PCT
      was earlier, even if much lower, on the first day. Then, they declined slowly
      approaching the baseline values by the second postoperative week. PCT mean values
      never exceed concentrations typically related to bacterial infections.
      CONCLUSIONS: CRP is very sensitive to inflammation. It could be the routine
      screening test in the follow-up of THA orthopaedic patients, but it should be
      complemented by PCT when there is the clinical suspicion of periprosthetic
      infection.

PMID- 24877116
TI  - The efficacy of balance training with video game-based therapy in subacute stroke
      patients: a randomized controlled trial.
AB  - The video game-based therapy emerged as a potential valid tool in improving
      balance in several neurological conditions with controversial results, whereas
      little information is available regarding the use of this therapy in subacute
      stroke patients. The aim of this study was to investigate the efficacy of balance
      training using video game-based intervention on functional balance and disability
      in individuals with hemiparesis due to stroke in subacute phase. Fifty adult
      stroke patients participated to the study: 25 subjects were randomly assigned to
      balance training with Wii Fit, and the other 25 subjects were assigned to usual
      balance therapy. Both groups were also treated with conventional physical therapy
      (40 min 2 times/day). The main outcome was functional balance (Berg Balance Scale
      BBS), and secondary outcomes were disability (Barthel Index-BI), walking ability
      (Functional Ambulation Category), and walking speed (10-meters walking test). Wii
      Fit training was more effective than usual balance therapy in improving balance
      (BBS: 53 versus 48, P = 0.004) and independency in activity of daily living (BI:
      98 versus 93, P = 0.021). A balance training performed with a Wii Fit as an add
      on to the conventional therapy was found to be more effective than conventional
      therapy alone in improving balance and reducing disability in patients with
      subacute stroke.

PMID- 24877115
TI  - An historical perspective on how advances in microscopic imaging contributed to
      understanding the Leishmania Spp. and Trypanosoma cruzi host-parasite
      relationship.
AB  - The literature has identified complex aspects of intracellular host-parasite
      relationships, which require systematic, nonreductionist approaches and
      spatial/temporal information. Increasing and integrating temporal and spatial
      dimensions in host cell imaging have contributed to elucidating several
      conceptual gaps in the biology of intracellular parasites. To access and
      investigate complex and emergent dynamic events, it is mandatory to follow them
      in the context of living cells and organs, constructing scientific images with
      integrated high quality spatiotemporal data. This review discusses examples of
      how advances in microscopy have challenged established conceptual models of the
      intracellular life cycles of Leishmania spp. and Trypanosoma cruzi protozoan
      parasites. 

PMID- 24877117
TI  - Motor training in degenerative spinocerebellar disease: ataxia-specific
      improvements by intensive physiotherapy and exergames.
AB  - The cerebellum is essentially involved in movement control and plays a critical
      role in motor learning. It has remained controversial whether patients with
      degenerative cerebellar disease benefit from high-intensity coordinative
      training. Moreover, it remains unclear by which training methods and mechanisms
      these patients might improve their motor performance. Here, we review evidence
      from different high-intensity training studies in patients with degenerative
      spinocerebellar disease. These studies demonstrate that high-intensity
      coordinative training might lead to a significant benefit in patients with
      degenerative ataxia. This training might be based either on physiotherapy or on
      whole-body controlled videogames ("exergames"). The benefit shown in these
      studies is equal to regaining one or more years of natural disease progression.
      In addition, first case studies indicate that even subjects with advanced
      neurodegeneration might benefit from such training programs. For both types of
      training, the observed clinical improvements are paralleled by recoveries in
      ataxia-specific dysfunctions (e.g., multijoint coordination and dynamic
      stability). Importantly, for both types of training, the retention of the effects
      seems to depend on the frequency and continuity of training. Based on these
      studies, we here present preliminary recommendations for clinical practice, and
      articulate open questions that might guide future studies on neurorehabilitation
      in degenerative spinocerebellar disease. 

PMID- 24877118
TI  - Exploring population pharmacokinetic modeling with resampling visualization.
AB  - BACKGROUND: In the last decade, population pharmacokinetic (PopPK) modeling has
      spread its influence in the whole process of drug research and development. While
      targeting the construction of the dose-concentration of a drug based on a
      population of patients, it shows great flexibility in dealing with sparse
      samplings and unbalanced designs. The resampling approach has been considered an
      important statistical tool to assist in PopPK model validation by measuring the
      uncertainty of parameter estimates and evaluating the influence of individuals.
      METHODS: The current work describes a graphical diagnostic approach for PopPK
      models by visualizing resampling statistics, such as case deletion and bootstrap.
      To examine resampling statistics, we adapted visual methods from multivariate
      analysis, parallel coordinate plots, and multidimensional scaling. RESULTS:
      Multiple models were fitted, the information of parameter estimates and
      diagnostics were extracted, and the results were visualized. With careful
      scaling, the dependencies between different statistics are revealed. Using
      typical examples, the approach proved to have great capacity to identify
      influential outliers from the statistical perspective, which deserves special
      attention in a dosing regimen. DISCUSSION: By combining static graphics with
      interactive graphics, we are able to explore the multidimensional data from an
      integrated and systematic perspective. Complementary to current approaches, our
      proposed method provides a new way for PopPK modeling analysis.

PMID- 24877119
TI  - Early treatment response monitoring using 2-deoxy-2-[ 18F]fluoro-D-glucose
      positron emission tomography imaging during fractionated radiotherapy of head
      neck cancer xenografts.
AB  - BACKGROUND: To determine the optimal timing and analytic method of 2-deoxy-2
      [(18)F]fluoro-D-glucose positron emission tomography (PET) imaging during
      fractionated radiotherapy (RT) to predict tumor control. METHODS: Ten head neck
      squamous cell carcinoma xenografts derived from the UT-14-SCC cell line were
      irradiated with 50 Gy at 2 Gy per day over 5 weeks. Dynamic PET scans were
      acquired over 70 minutes at baseline (week 0) and weekly for seven weeks. PET
      data were analyzed using standard uptake value (SUV), retention index (RI),
      sensitivity factor (SF), and kinetic index (Ki). RESULTS: Four xenografts had
      local failure (LF) and 6 had local control. Eighty scans from week 0 to week 7
      were analyzed. RI and SF after 10 Gy appeared to be the optimal predictors for
      LF. In contrast, SUV and Ki during RT were not significant predictors for LF.
      CONCLUSION: RI and SF of PET obtained after the first week of fractionated RT
      were the optimal methods and timing to predict tumor control.

PMID- 24877120
TI  - Anti-inflammatory effects of the nicotinergic peptides SLURP-1 and SLURP-2 on
      human intestinal epithelial cells and immunocytes.
AB  - A search for novel and more efficient therapeutic modalities of inflammatory
      bowel disease (IBD) is one of the most important tasks of contemporary medicine.
      The anti-inflammatory action of nicotine in IBD might be therapeutic, but its
      toxicity due to off-target and nonreceptor effects limited its use and prompted a
      search for nontoxic nicotinergic drugs. We tested the hypothesis that SLURP-1 and
      -2--the physiological nicotinergic substances produced by the human intestinal
      epithelial cells (IEC) and immunocytes--can mimic the anti-inflammatory effects
      of nicotine. We used human CCL-241 enterocytes, CCL-248 colonocytes, CCRF-CEM T
      cells, and U937 macrophages. SLURP-1 diminished the TLR9-dependent secretion of
      IL-8 by CCL-241, and IFN gamma-induced upregulation of ICAM-1 in both IEC types.
      rSLURP-2 inhibited IL-1 beta-induced secretion of IL-6 and TLR4- and TLR9
      dependent induction of CXCL10 and IL-8, respectively, in CCL-241. rSLURP-1
      decreased production of TNFalpha by T-cells, downregulated IL-1 beta and IL-6
      secretion by macrophages, and moderately upregulated IL-10 production by both
      types of immunocytes. SLURP-2 downregulated TNFalpha and IFNgamma R in T-cells
      and reduced IL-6 production by macrophages. Combining both SLURPs amplified their
      anti-inflammatory effects. Learning the pharmacology of SLURP-1 and -2 actions on
      enterocytes, colonocytes, T cells, and macrophages may help develop novel
      effective treatments of IBD.

PMID- 24877122
TI  - Impairment of electron transfer chain induced by acute carnosine administration
      in skeletal muscle of young rats.
AB  - Serum carnosinase deficiency is an inherited disorder that leads to an
      accumulation of carnosine in the brain tissue, cerebrospinal fluid, skeletal
      muscle, and other tissues of affected patients. Considering that high levels of
      carnosine are associated with neurological dysfunction and that the
      pathophysiological mechanisms involved in serum carnosinase deficiency remain
      poorly understood, we investigated the in vivo effects of carnosine on
      bioenergetics parameters, namely, respiratory chain complexes (I-III, II, and II
      III), malate dehydrogenase, succinate dehydrogenase, and creatine kinase
      activities and the expression of mitochondrial-specific transcription factors
      (NRF-1, PGC-1alpha , and TFAM) in skeletal muscle of young Wistar rats. We
      observed a significant decrease of complexes I-III and II activities in animals
      receiving carnosine acutely, as compared to control group. However, no
      significant alterations in respiratory chain complexes, citric acid cycle
      enzymes, and creatine kinase activities were found between rats receiving
      carnosine chronically and control group animals. As compared to control group,
      mRNA levels of NRF-1, PGC-1alpha , and TFAM were unchanged. The present findings
      indicate that electron transfer through the respiratory chain is impaired in
      skeletal muscle of rats receiving carnosine acutely. In case these findings are
      confirmed by further studies and ATP depletion is also observed, impairment of
      bioenergetics could be considered a putative mechanism responsible for the muscle
      damage observed in serum carnosinase-deficient patients. 

PMID- 24877121
TI  - Mannan-binding lectin in cardiovascular disease.
AB  - Cardiovascular disease remains the leading cause of mortality and morbidity
      worldwide so research continues into underlying mechanisms. Since innate immunity
      and its potent component mannan-binding lectin have been proven to play an
      important role in the inflammatory response during infection and ischaemia
      reperfusion injury, attention has been paid to its role in the development of
      cardiovascular complications as well. This review provides a general outline of
      the structure and genetic polymorphism of MBL and its role in inflammation/tissue
      injury with emphasis on associations with cardiovascular disease. MBL appears to
      be involved in the pathogenesis of atherosclerosis and, in consequence, coronary
      artery disease and also inflammation and tissue injury after myocardial
      infarction and heart transplantation. The relationship between MBL and disease is
      rather complex and depends on different genetic and environmental factors. That
      could be why the data obtained from animal and clinical studies are sometimes
      contradictory proving not for the first time that innate immunity is a "double
      edge sword," sometimes beneficial and, at other times disastrous for the host. 

PMID- 24877124
TI  - The role of uric acid in kidney fibrosis: experimental evidences for the causal
      relationship.
AB  - Hyperuricemia is a common finding in chronic kidney disease due to decreased uric
      acid clearance. The role of uric acid as a risk factor for chronic kidney disease
      has been largely debated, and recent studies suggested a role of uric acid in the
      causation and progression of kidney fibrosis, a final common pathway in chronic
      kidney disease. Uric acid and xanthine oxidase may contribute to kidney fibrosis
      mainly by inducing inflammation, endothelial dysfunction, oxidative stress, and
      activation of the renin-angiotensin system. Besides, hyperuricemia induces
      alterations in renal hemodynamics via afferent arteriolopathy and contributes to
      the onset and progression of kidney fibrosis. Xanthine oxidase inhibitors may
      prevent kidney damage via lowering uric acid and/or inhibiting xanthine oxidase.
      However, there is still no sufficient evidence from interventional clinical
      researches supporting the causal relationship between uric acid and kidney
      fibrosis. The effect and role of xanthine oxidase inhibitors in preventing kidney
      fibrosis and chronic kidney disease progression must be further explored by
      performing future large scale clinical trials. 

PMID- 24877123
TI  - Effects of hypertension and exercise on cardiac proteome remodelling.
AB  - Left ventricle hypertrophy is a common outcome of pressure overload stimulus
      closely associated with hypertension. This process is triggered by adverse
      molecular signalling, gene expression, and proteome alteration. Proteomic
      research has revealed that several molecular targets are associated with
      pathologic cardiac hypertrophy, including angiotensin II, endothelin-1 and
      isoproterenol. Several metabolic, contractile, and stress-related proteins are
      shown to be altered in cardiac hypertrophy derived by hypertension. On the other
      hand, exercise is a nonpharmacologic agent used for hypertension treatment, where
      cardiac hypertrophy induced by exercise training is characterized by improvement
      in cardiac function and resistance against ischemic insult. Despite the scarcity
      of proteomic research performed with exercise, healthy and pathologic heart
      proteomes are shown to be modulated in a completely different way. Hence, the
      altered proteome induced by exercise is mostly associated with cardioprotective
      aspects such as contractile and metabolic improvement and physiologic cardiac
      hypertrophy. The present review, therefore, describes relevant studies involving
      the molecular characteristics and alterations from hypertensive-induced and
      exercise-induced hypertrophy, as well as the main proteomic research performed in
      this field. Furthermore, proteomic research into the effect of hypertension on
      other target-demerged organs is examined. 

PMID- 24877125
TI  - MAS-mediated antioxidant effects restore the functionality of angiotensin
      converting enzyme 2-angiotensin-(1-7)-MAS axis in diabetic rat carotid.
AB  - We hypothesized that endothelial AT1-activated NAD(P)H oxidase-driven generation
      of reactive oxygen species during type I-diabetes impairs carotid ACE2
      angiotensin-(1-7)-Mas axis functionality, which accounts for the impaired carotid
      flow in diabetic rats. We also hypothesized that angiotensin-(1-7) chronic
      treatment of diabetic rats restores carotid ACE2-angiotensin-(1-7)-Mas axis
      functionality and carotid flow. Relaxant curves for angiotensin II or angiotensin
      (1-7) were obtained in carotid from streptozotocin-induced diabetic rats.
      Superoxide or hydrogen peroxide levels were measured by flow cytometry in carotid
      endothelial cells. Carotid flow was also determined. We found that endothelial
      AT1-activated NAD(P)H oxidase-driven generation of superoxide and hydrogen
      peroxide in diabetic rat carotid impairs ACE2-angiotensin-(1-7)-Mas axis
      functionality, which reduces carotid flow. In this mechanism, hydrogen peroxide
      derived from superoxide dismutation inhibits ACE2 activity in generating
      angiotensin-(1-7) seemingly by activating I(Cl,SWELL0, while superoxide inhibits
      the nitrergic Mas-mediated vasorelaxation evoked by angiotensin-(1-7).
      Angiotensin-(1-7) treatment of diabetic rats restored carotid ACE2-angiotensin-(1
      7)-Mas axis functionality by triggering a positive feedback played by endothelial
      Mas receptors, that blunts endothelial AT1-activated NAD(P)H oxidase-driven
      generation of reactive oxygen species. Mas-mediated antioxidant effects also
      restored diabetic rat carotid flow, pointing to the contribution of ACE2
      angiotensin-(1-7)-Mas axis in maintaining carotid flow.

PMID- 24877129
TI  - In vivo antistress and antioxidant effects of fermented and germinated mung bean.
AB  - Mung bean has been traditionally used to alleviate heat stress. This effect may
      be contributed by the presence of flavonoids and gamma-aminobutyric acid (GABA).
      On the other hand, fermentation and germination have been practised to enhance
      the nutritional and antioxidant properties of certain food products. The main
      focus of current study was to compare the antistress effect of none-process,
      fermented and germinated mung bean extracts. Acute and chronic restraint stresses
      were observed to promote the elevation of serum biochemical markers including
      cholesterol, triglyceride, total protein, liver enzymes, and glucose. Chronic
      cold restraint stress was observed to increase the adrenal gland weight, brain 5
      hydroxytryptamine (5-HT), and malondialdehyde (MDA) level while reducing brain
      antioxidant enzyme level. However, these parameters were found reverted in mice
      treated with diazepam, high concentration of fermented mung bean and high
      concentration of germinated mung bean. Moreover, enhanced level of antioxidant on
      the chronic stress mice was observed in fermented and germinated mung bean
      treated groups. In comparison between germinated and fermented mung bean,
      fermented mung bean always showed better antistress and antioxidant effects
      throughout this study.

PMID- 24877128
TI  - Inflammatory profiling of Schwann cells in contact with growing axons distal to
      nerve injury.
AB  - Activated Schwann cells distal to nerve injury upregulate inflammatory mediators,
      including cytokines. The goal of the present study was to investigate expression
      of proinflammatory (IL-1beta, TNFalpha) and anti-inflammatory cytokines (IL-4, IL
      10) in activated Schwann cells in relation to growing axons distal to crush
      injury of rat sciatic nerves. Seven days from sciatic nerve crush, transverse
      cryostat sections were cut 5 mm distal to lesion and incubated for double
      immunostaining to indicate Schwann cells (GFAP or S100b) and individual
      investigated cytokines or to demonstrate growing axons (GAP43). The Schwann cells
      of naive sciatic nerves and those removed from sham-operated rats displayed
      similar weak immunoreactivity for the investigated cytokines. In contrast,
      increased intensity of cytokine immunofluorescence was found in Schwann cells
      distal to crush lesion. The cytokine-positive Schwann cells were found in close
      contact with growing axons detected by immunostaining for GAP43. The results of
      immunohistochemical analysis distal to nerve crush injury suggest that
      inflammatory profiling of Schwann cells including upregulation of both pro- and
      anti-inflammatory cytokines does not prevent growth of axons distal to nerve
      crush injury.

PMID- 24877127
TI  - B cells in rheumatoid arthritis: from pathogenic players to disease biomarkers.
AB  - The therapeutic benefit of depleting B cells in rheumatoid arthritis (RA) has
      refocused attention on B cells with increasing awareness on their role in
      autoimmunity and their function beyond autoantibody production. The rapid
      increase in our comprehension of B-cell pathobiology is progressively opening
      novel perspectives in the area of B cell-targeted therapies with the expectation
      to define more specific approaches able to preserve the homeostasis of the
      humoral response while disrupting the pathogenic components. In parallel, B-cell
      activity in RA is starting to be explored in its clinical value, in search of
      novel biomarkers embedded in the pathogenic process that could help classifying
      the disease and predicting its heterogeneous outcome beyond inflammation
      dynamics. In this review, we summarize current knowledge on the multiple roles
      that B cells play in several aspects of RA. We also analyze their distribution
      and potential function in different anatomic compartments with specific reference
      to the main sites in which the disease may be sustained and exert its detrimental
      effects: the systemic circulation, synovium, bone marrow, and draining lymph
      nodes. We also highlight novel data encouraging further research in the field of
      biomarkers related to B cells and their regulatory factors. 

PMID- 24877130
TI  - The importance of the ionic product for water to understand the physiology of the
      acid-base balance in humans.
AB  - Human plasma is an aqueous solution that has to abide by chemical rules such as
      the principle of electrical neutrality and the constancy of the ionic product for
      water. These rules define the acid-base balance in the human body. According to
      the electroneutrality principle, plasma has to be electrically neutral and the
      sum of its cations equals the sum of its anions. In addition, the ionic product
      for water has to be constant. Therefore, the plasma concentration of hydrogen
      ions depends on the plasma ionic composition. Variations in the concentration of
      plasma ions that alter the relative proportion of anions and cations predictably
      lead to a change in the plasma concentration of hydrogen ions by driving adaptive
      adjustments in water ionization that allow plasma electroneutrality while
      maintaining constant the ionic product for water. The accumulation of plasma
      anions out of proportion of cations induces an electrical imbalance compensated
      by a fall of hydroxide ions that brings about a rise in hydrogen ions (acidosis).
      By contrast, the deficiency of chloride relative to sodium generates plasma
      alkalosis by increasing hydroxide ions. The adjustment of plasma bicarbonate
      concentration to these changes is an important compensatory mechanism that
      protects plasma pH from severe deviations. 

PMID- 24877131
TI  - Analysis of the virulence of an atypical enteropathogenic Escherichia coli strain
      in vitro and in vivo and the influence of type three secretion system.
AB  - Atypical enteropathogenic Escherichia coli (aEPEC) inject various effectors into
      intestinal cells through a type three secretion system (T3SS), causing attaching
      and effacing (A/E) lesions. We investigated the role of T3SS in the ability of
      the aEPEC 1711-4 strain to interact with enterocytes in vitro (Caco-2 cells) and
      in vivo (rabbit ileal loops) and to translocate the rat intestinal mucosa in
      vivo. A T3SS isogenic mutant strain was constructed, which showed marked
      reduction in the ability to associate and invade but not to persist inside Caco-2
      cells. After rabbit infection, only aEPEC 1711-4 was detected inside enterocytes
      at 8 and 24 hours pointing to a T3SS-dependent invasive potential in vivo. In
      contrast to aEPEC 1711-4, the T3SS-deficient strain no longer produced A/E
      lesions or induced macrophage infiltration. We also demonstrated that the ability
      of aEPEC 1711-4 to translocate through mesenteric lymph nodes to spleen and liver
      in a rat model depends on a functional T3SS, since a decreased number of T3SS
      mutant bacteria were recovered from extraintestinal sites. These findings
      indicate that the full virulence potential of aEPEC 1711-4 depends on a
      functional T3SS, which contributes to efficient adhesion/invasion in vitro and in
      vivo and to bacterial translocation to extraintestinal sites. 

PMID- 24877134
TI  - Endothelium in diseased states.

PMID- 24877132
TI  - In vitro chronic administration of ERbeta selective ligands and prostate cancer
      cell growth: hypotheses on the selective role of 3beta-adiol in AR-positive RV1
      cells.
AB  - Prostate cancer (PC) progression from androgen-dependent (AD) to castration
      resistant (CR) disease is a process caused by modifications of different signal
      transduction pathways within tumor microenvironment. Reducing cell proliferation,
      estrogen receptor beta (ERbeta) is emerging as a potential target in PC
      chemoprevention. Among the known selective ERbeta ligands, 3beta-Adiol, the
      endogenous ligand in the prostate, has been proved to counteract PC progression.
      This study compares the effects of chronic exposure (1-12 weeks) to different
      ERbeta selective ligands (DPN, 8beta-VE2, 3beta-Adiol) on proliferation of human
      androgen-responsive CWR22Rv1 cells, representing an intermediate phenotype
      between the AD- and CR-PC. 3beta-Adiol (10 nM) is the sole ligand decreasing cell
      proliferation and increasing p21 levels. In vitro transcriptional activity assays
      were performed to elucidate different behavior between 3beta-Adiol and the other
      ligands; in these experiments the endogenous and the main ERbeta subtype
      activation were considered. It is concluded that ERbeta activation has positive
      effects also in androgen-responsive PC. The underlying mechanisms are still to be
      clarified and may include the interplay among different ERbeta subtypes and the
      specific PC microenvironment. ERbeta agonists might be useful in counteracting PC
      progression, although the final outcome may depend upon the molecular pattern
      specific to each PC lesion. 

PMID- 24877136
TI  - Recent developments in mycobacteriology: a clinical and diagnostic perspective.

PMID- 24877135
TI  - Differences in swallowing between high and low concentration taste stimuli.
AB  - Taste is a property that is thought to potentially modulate swallowing behavior.
      Whether such effects depend on taste, intensity remains unclear. This study
      explored differences in the amplitudes of tongue-palate pressures in swallowing
      as a function of taste stimulus concentration. Tongue-palate pressures were
      collected in 80 healthy women, in two age groups (under 40, over 60), stratified
      by genetic taste status (nontasters, supertasters). Liquids with different taste
      qualities (sweet, sour, salty, and bitter) were presented in high and low
      concentrations. General labeled magnitude scale ratings captured perceived taste
      intensity and liking/disliking of the test liquids. Path analysis explored
      whether factors of taste, concentration, age group, and/or genetic taste status
      impacted: (1) perceived intensity; (2) palatability; and (3) swallowing
      pressures. Higher ratings of perceived intensity were found in supertasters and
      with higher concentrations, which were more liked/disliked than lower
      concentrations. Sweet stimuli were more palatable than sour, salty, or bitter
      stimuli. Higher concentrations elicited stronger tongue-palate pressures
      independently and in association with intensity ratings. The perceived intensity
      of a taste stimulus varies as a function of stimulus concentration, taste
      quality, participant age, and genetic taste status and influences swallowing
      pressure amplitudes. High-concentration salty and sour stimuli elicit the
      greatest tongue-palate pressures. 

PMID- 24877133
TI  - The Yin and Yang of innate immunity in stroke.
AB  - Immune system plays an elementary role in the pathophysiological progress of
      ischemic stroke. It consists of innate and adaptive immune system. Activated
      within minutes after ischemic onset, innate immunity is responsible for the
      elimination of necrotic cells and tissue repair, while it is critically involved
      in the initiation and amplification of poststroke inflammation that amplifies
      ischemic damage to the brain tissue. Innate immune response requires days to be
      fully developed, providing a considerable time window for therapeutic
      intervention, suggesting prospect of novel immunomodulatory therapies against
      poststroke inflammation-induced brain injury. However, obstacles still exist and
      a comprehensive understanding of ischemic stroke and innate immune reaction is
      essential. In this review, we highlighted the current experimental and clinical
      data depicting the innate immune response following ischemic stroke, mainly
      focusing on the recognition of damage-associated molecular patterns, activation
      and recruitment of innate immune cells, and involvement of various cytokines. In
      addition, clinical trials targeting innate immunity were also documented
      regardless of the outcome, stressing the requirements for further investigation. 

PMID- 24877137
TI  - Measurement of bed turning and comparison with age, gender, and body mass index
      in a healthy population: application of a novel mobility detection system.
AB  - We developed a mobility detection system to analyze pressure changes over time
      during side-turns in 29 healthy volunteers (17 males and 12 females) with a mean
      age of 46.1 +/- 19.64 years (ranging from 23 to 86 years) in order to determine
      the effect of gender, age, and BMI on performance during bed postural change.
      Center of gravity (COG) location, peak pressure of counteraction, and time to
      reach peak pressure were the main outcomes used to gauge the ability to make a
      spontaneous side-turn. Men exhibited significantly higher side-turning force (P =
      0.002) and back-turning force (P = 0.002) compared with women. Subjects with BMI
      >= 27 kg/m(2) had significantly higher side-turning force (P = 0.007) and back
      turning force (P = 0.007) compared with those with BMI < 27 kg/m(2). After
      adjusting for other covariates, age positively correlated with back-turning time
      (P = 0.033) and negatively correlated with side-turning speed (P = 0.005), back
      turning speed (P = 0.014), side-turning force (P = 0.010), and back-turning force
      (P = 0.016), respectively. Turning times negatively correlated with time to reach
      peak pressure (P = 0.008). Our system was effective in detecting changes in
      turning swiftness in the bed-ridden subject.

PMID- 24877138
TI  - In vitro antiplasmodial activities and synergistic combinations of differential
      solvent extracts of the polyherbal product, Nefang.
AB  - Nefang, a polyherbal product composed of Mangifera indica (bark and leaf),
      Psidium guajava, Carica papaya, Cymbopogon citratus, Citrus sinensis, and Ocimum
      gratissimum (leaves), is a potential therapy against P. falciparum malaria. In
      vitro antiplasmodial activities of its constituent solvent extracts were analyzed
      on CQ-sensitive (3D7) and multidrug resistant (Dd2) P. falciparum strains. The
      interactions involving the differential solvent extracts were further analyzed
      using a variable potency ratio drug combination approach. Effective concentration
      50 (EC50) values were determined by nonlinear regression curve-fitting of the
      dose-response data and used in calculating the fractional inhibitory
      concentration 50 (FIC50) and combination indices (CI) for each pair. The derived
      EC50 values (3D7/Dd2, MU g/mL) are Nefang-96.96/55.08, MiB-65.33/34.58, MiL
      82.56/40.04, Pg-47.02/25.79, Cp-1188/317.5, Cc-723.3/141, Cs-184.4/105.1, and Og
      778.5/118.9. Synergism was obtained with MiB/Pg (CI = 0.351), MiL/Pg (0.358),
      MiB/Cs (0.366), MiL/Cs (0.482), Pg/Cs (0.483), and Cs/Og (0.414) when analyzed at
      equipotency ratios. Cytotoxicity testing of Nefang and the solvent extracts on
      two human cell lines (Hep G2 and U2OS) revealed no significant toxicity relative
      to their antiplasmodial activities (SI > 20). Taken together, our data confirm
      the antimalarial activities of Nefang and its constituent plant extracts and
      identified extract pairs with promising synergistic interactions for exploitation
      towards a rational phytotherapeutic and evidence-based antimalarial drug
      discovery. 

PMID- 24877140
TI  - Calcium influx and male fertility in the context of the sperm proteome: an
      update.
AB  - Freshly ejaculated spermatozoa are incapable or poorly capable of fertilizing an
      oocyte. The fertilization aptness of spermatozoa depends on the appropriate and
      time-dependent acquisition of hyperactivation, chemotaxis, capacitation, and the
      acrosome reaction, where calcium (Ca(2+)) is extensively involved in almost every
      step. A literature review showed that several ion channel proteins are likely
      responsible for regulation of the Ca(2+) uptake in spermatozoa. Therefore,
      manipulation of the functions of channel proteins is closely related to Ca(2+)
      influx, ultimately affecting male fertility. Recently, it has been shown that,
      together with different physiological stimuli, protein-protein interaction also
      modifies the Ca(2+) influx mechanism in spermatozoa. Modern proteomic analyses
      have identified several sperm proteins, and, therefore, these findings might
      provide further insight into understanding the Ca(2+) influx, protein functions,
      and regulation of fertility. The objective of this review was to synthesize the
      published findings on the Ca(2+) influx mechanism in mammalian spermatozoa and
      its implications for the regulation of male fertility in the context of sperm
      proteins. Finally, Pathway Studio (9.0) was used to catalog the sperm proteins
      that regulate the Ca(2+) influx signaling by using the information available from
      the PubMed database following a MedScan Reader (5.0) search. 

PMID- 24877141
TI  - Development and retranslational validation of an in vitro model to characterize
      acute infections in large human joints.
AB  - Bacterial infections can destroy cartilage integrity, resulting in
      osteoarthritis. Goal was to develop an in vitro model with in vivo validation of
      acute joint inflammation. Inflammation in cocultivated human synovial fibroblasts
      (SFB), chondrocytes (CHDR), and mononuclear cells (MNC) was successively relieved
      for 10 days. Articular effusions from patients with (n = 7) and without (n = 5)
      postoperative joint infection in healthy patients (ASA 1-2) were used as model
      validation. Inflammation in vitro resulted in an enormous increase in IL-1 and a
      successive reduction in SFB numbers. CHDR however, maintained metabolic activity
      and proteoglycan synthesis. While concentrations of bFGF in vivo and in vitro
      rose consistently, the mRNA increase was only moderate. Concurring with our in
      vivo data, cartilage-specific IGF-1 steadily increased, while IGF-1 mRNA in the
      CHDR and SFB did not correlate with protein levels. Similarly, aggrecan (ACAN)
      protein concentrations increased in vivo and failed to correlate in vitro with
      gene expression in either the CHDR or the SFB, indicating extracellular matrix
      breakdown. Anabolic cartilage-specific BMP-7 with highly significant intra
      articular levels was significantly elevated in vitro on day 10 following maximum
      inflammation. Our in vitro model enables us to validate early inflammation of in
      vivo cell- and cytokine-specific regulatory patterns. This trial is registered
      with MISSinG, DRKS 00003536. 

PMID- 24877142
TI  - Accumulation of misfolded SOD1 in dorsal root ganglion degenerating
      proprioceptive sensory neurons of transgenic mice with amyotrophic lateral
      sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is an adult-onset progressive
      neurodegenerative disease affecting upper and lower motoneurons (MNs). Although
      the motor phenotype is a hallmark for ALS, there is increasing evidence that
      systems other than the efferent MN system can be involved. Mutations of
      superoxide dismutase 1 (SOD1) gene cause a proportion of familial forms of this
      disease. Misfolding and aggregation of mutant SOD1 exert neurotoxicity in a
      noncell autonomous manner, as evidenced in studies using transgenic mouse models.
      Here, we used the SOD1(G93A) mouse model for ALS to detect, by means of
      conformational-specific anti-SOD1 antibodies, whether misfolded SOD1-mediated
      neurotoxicity extended to neuronal types other than MNs. We report that large
      dorsal root ganglion (DRG) proprioceptive neurons accumulate misfolded SOD1 and
      suffer a degenerative process involving the inflammatory recruitment of
      macrophagic cells. Degenerating sensory axons were also detected in association
      with activated microglial cells in the spinal cord dorsal horn of diseased
      animals. As large proprioceptive DRG neurons project monosynaptically to ventral
      horn MNs, we hypothesise that a prion-like mechanism may be responsible for the
      transsynaptic propagation of SOD1 misfolding from ventral horn MNs to DRG sensory
      neurons. 

PMID- 24877139
TI  - Cartilage repair surgery: outcome evaluation by using noninvasive cartilage
      biomarkers based on quantitative MRI techniques?
AB  - BACKGROUND: New quantitative magnetic resonance imaging (MRI) techniques are
      increasingly applied as outcome measures after cartilage repair. OBJECTIVE: To
      review the current literature on the use of quantitative MRI biomarkers for
      evaluation of cartilage repair at the knee and ankle. METHODS: Using PubMed
      literature research, studies on biochemical, quantitative MR imaging of cartilage
      repair were identified and reviewed. RESULTS: Quantitative MR biomarkers detect
      early degeneration of articular cartilage, mainly represented by an increasing
      water content, collagen disruption, and proteoglycan loss. Recently, feasibility
      of biochemical MR imaging of cartilage repair tissue and surrounding cartilage
      was demonstrated. Ultrastructural properties of the tissue after different repair
      procedures resulted in differences in imaging characteristics. T2 mapping, T1rho
      mapping, delayed gadolinium-enhanced MRI of cartilage (dGEMRIC), and diffusion
      weighted imaging (DWI) are applicable on most clinical 1.5 T and 3 T MR scanners.
      Currently, a standard of reference is difficult to define and knowledge is
      limited concerning correlation of clinical and MR findings. The lack of
      histological correlations complicates the identification of the exact tissue
      composition. CONCLUSIONS: A multimodal approach combining several quantitative
      MRI techniques in addition to morphological and clinical evaluation might be
      promising. Further investigations are required to demonstrate the potential for
      outcome evaluation after cartilage repair.

PMID- 24877143
TI  - Association between autoimmune rheumatic diseases and the risk of dementia.
AB  - AIM: Autoimmune rheumatic diseases (ARD) are characterized by systemic
      inflammation and may affect multiple organs and cause vascular events such as
      ischemic stroke and acute myocardial infarction. However, the association between
      ARD and increased risk of dementia is uncertain. This is a retrospective cohort
      study to investigate and compare the risk of dementia between patients clinically
      diagnosed with ARD and non-ARD patients during a 5-year follow-up period.
      METHODS: Data were obtained from the Longitudinal Health Insurance Database 2000
      (LHID2000). We included 1221 patients receiving ambulatory or hospitalization
      care and 6105 non-ARD patients; patients were matched by sex, age, and the year
      of index use of health care. Each patient was studied for 5 years to identify the
      subsequent manifestation of dementia. The data obtained were analyzed by Cox
      proportional hazard regression. RESULTS: During the 5-year follow-up period, 30
      ARD (2.48%) and 141 non-ARD patients (2.31%) developed dementia. During the 5
      year follow-up period, there were no significant differences in the risks of any
      type of dementia (adjusted hazard ratio (HR), 1.18; 95% CI, 0.79-1.76) in the ARD
      group after adjusting for demographics and comorbidities. CONCLUSIONS: Within the
      5-year period, patients with and without ARD were found to have similar risks of
      developing dementia.

PMID- 24877144
TI  - Role of calcium signaling in the transcriptional regulation of the apicoplast
      genome of Plasmodium falciparum.
AB  - Calcium is a universal second messenger that plays an important role in
      regulatory processes in eukaryotic cells. To understand calcium-dependent
      signaling in malaria parasites, we analyzed transcriptional responses of
      Plasmodium falciparum to two calcium ionophores (A23187 and ionomycin) that cause
      redistribution of intracellular calcium within the cytoplasm. While ionomycin
      induced a specific transcriptional response defined by up- or downregulation of a
      narrow set of genes, A23187 caused a developmental arrest in the schizont stage.
      In addition, we observed a dramatic decrease of mRNA levels of the transcripts
      encoded by the apicoplast genome during the exposure of P. falciparum to both
      calcium ionophores. Neither of the ionophores caused any disruptions to the DNA
      replication or the overall apicoplast morphology. This suggests that the mRNA
      downregulation reflects direct inhibition of the apicoplast gene transcription.
      Next, we identify a nuclear encoded protein with a calcium binding domain (EF
      hand) that is localized to the apicoplast. Overexpression of this protein (termed
      PfACBP1) in P. falciparum cells mediates an increased resistance to the
      ionophores which suggests its role in calcium-dependent signaling within the
      apicoplast. Our data indicate that the P. falciparum apicoplast requires calcium
      dependent signaling that involves a novel protein PfACBP1. 

PMID- 24877146
TI  - Variations in KIR genes: a study in HIV-1 serodiscordant couples.
AB  - BACKGROUND: NK cells have anti-HIV activity mediated through killer cell
      immunoglobulin-like receptors (KIRs). The current prospective cohort study
      evaluated whether variation in KIR genes is associated with HIV infection in
      discordant couples (DCs), where one spouse remains seronegative (HSN) despite
      repeated exposure to the HIV. METHODS: KIR was genotyped using PCR SSP. Viral
      load and CD4 counts were estimated using commercially available reagents. Data
      were analyzed using SPSS software. RESULTS: Among the 47 DCs, HSN spouses had
      significantly (P = 0.006) higher frequencies of KIR3DS1. Regression analysis
      revealed significant (P = 0.009) association of KIR2DS1 with low viral load.
      KIR2DS4 variant was associated (P = 0.032) with high viral load. Three pairs of
      KIR genes were in strong LD in HSNs and two pairs in HSPs. There were 60 KIR
      genotypes, and 16 are reported the first time in the Indian population. Exclusive
      genotypes were present either in HSPs (N = 22, 11 unique genotypes) or in HSNs (n
      = 27, 9 unique genotypes). CONCLUSIONS: This study highlights for the first time
      in the Indian population an association of KIR genes in HIV infection where
      presence of exclusive and unique genotypes indicates possible association with
      either HIV infection or with protection.

PMID- 24877145
TI  - Novel tools for prostate cancer prognosis, diagnosis, and follow-up.
AB  - Prostate-specific antigen (PSA) is the main diagnostic tool when it comes to
      prostate cancer but it possesses serious limitations. Therefore, there is an
      urgent need for more sensitive and specific biomarkers for prostate cancer
      prognosis and patient follow-up. Recent advances led to the discovery of many
      novel diagnostic/prognostic techniques and provided us with many worthwhile
      candidates. This paper briefly reviews the most promising biomarkers with respect
      to their implementation in screening, early detection, diagnostic confirmation,
      prognosis, and prediction of therapeutic response or monitoring disease and
      recurrence; and their use as possible therapeutic targets. This review also
      examines the possible future directions in the field of prostate cancer marker
      research. 

PMID- 24877147
TI  - The urethral rhabdosphincter, levator ani muscle, and perineal membrane: a
      review.
AB  - Detailed knowledge of the anatomy of the rhabdosphincter and adjacent tissues is
      mandatory during urologic surgery to ensure reliable oncologic and functional
      outcomes. To characterize the levator ani (LA) function for the urethral
      sphincter, we described connective tissue morphology between the LA and urethral
      rhabdosphincter. The interface tissue between the LA and rhabdosphincter area in
      males contained abundant irregularly arrayed elastic fibers and smooth muscles.
      The male rhabdosphincter was positioned alongside the LA to divide the elevation
      force and not in-series along the axis of LA contraction. The male perineal
      membrane was thin but solid and extends along the inferior margin or bottom of
      the rhabdosphincter area. In contrast, the female rhabdosphincter, including the
      compressor urethrae and urethrovaginal sphincter muscles, was embedded in the
      elastic fiber mesh that is continuous with the thick, multilaminar perineal
      membrane. The inferomedial edge of the female LA was attached to the upper
      surface of the perineal membrane and not directly attached to the
      rhabdosphincter. We presented new diagrams showing the gender differences in
      topographical anatomy of the LA and rhabdosphincter. 

PMID- 24877148
TI  - Current innovations in endoscopic therapy for the management of colorectal
      cancer: from endoscopic submucosal dissection to endoscopic full-thickness
      resection.
AB  - Endoscopic submucosal dissection (ESD) is accepted as a minimally invasive
      treatment for colorectal cancer. However, due to technical difficulties and an
      increased rate of complications, ESD is not widely used in the colorectum. In
      some cases, endoscopic treatment alone is insufficient for disease control, and
      laparoscopic surgery is required. The combination of laparoscopic surgery and
      endoscopic resection represents a new frontier in cancer treatment. Recent
      developments in advanced polypectomy and minimally invasive surgical techniques
      will enable surgeons and endoscopists to challenge current practice in colorectal
      cancer treatment. Endoscopic full-thickness resection (EFTR) of the colon offers
      the potential to decrease the postoperative morbidity and mortality associated
      with segmental colectomy while enhancing the diagnostic yield compared to current
      endoscopic techniques. However, closure is necessary after EFTR and natural
      transluminal endoscopic surgery (NOTES). Innovative methods and new devices for
      EFTR and suturing are being developed and may potentially change traditional
      paradigms to achieve minimally invasive surgery for colorectal cancer. The
      present paper aims to discuss the complementary role of ESD and the future
      development of EFTR. We focus on the possibility of achieving EFTR using the ESD
      method and closing devices. 

PMID- 24877149
TI  - Homeobox genes and melatonin synthesis: regulatory roles of the cone-rod homeobox
      transcription factor in the rodent pineal gland.
AB  - Nocturnal synthesis of melatonin in the pineal gland is controlled by a circadian
      rhythm in arylalkylamine N-acetyltransferase (AANAT) enzyme activity. In the
      rodent, Aanat gene expression displays a marked circadian rhythm; release of
      norepinephrine in the gland at night causes a cAMP-based induction of Aanat
      transcription. However, additional transcriptional control mechanisms exist.
      Homeobox genes, which are generally known to encode transcription factors
      controlling developmental processes, are also expressed in the mature rodent
      pineal gland. Among these, the cone-rod homeobox (CRX) transcription factor is
      believed to control pineal-specific Aanat expression. Based on recent advances in
      our understanding of Crx in the rodent pineal gland, we here suggest that
      homeobox genes play a role in adult pineal physiology both by ensuring pineal
      specific Aanat expression and by facilitating cAMP response element-based
      circadian melatonin production. 

PMID- 24877150
TI  - Endometrial receptivity profile in patients with premature progesterone elevation
      on the day of HCG administration.
AB  - The impact of a premature elevation of serum progesterone level, the day of hCG
      administration in patients under controlled ovarian stimulation during IVF
      procedure, on human endometrial receptivity is still debated. In the present
      study, we investigated the endometrial gene expression profile shifts during the
      prereceptive and receptive secretory stage in patients with normal and elevated
      serum progesterone level on the day of hCG administration in fifteen patients
      under stimulated cycles. Then, specific biomarkers of endometrial receptivity in
      these two groups of patients were tested. Endometrial biopsies were performed on
      oocyte retrieval day and on day 3 of embryo transfer, respectively, for each
      patient. Samples were analysed using DNA microarrays and qRT-PCR. The endometrial
      gene expression shift from the prereceptive to the receptive stage was altered in
      patients with high serum progesterone level (>1.5 ng/mL) on hCG day, suggesting
      accelerated endometrial maturation during the periovulation period. This was
      confirmed by the functional annotation of the differentially expressed genes as
      it showed downregulation of cell cycle-related genes. Conversely, the profile of
      endometrial receptivity was comparable in both groups. Premature progesterone
      rise alters the endometrial gene expression shift between the prereceptive and
      the receptive stage but does not affect endometrial receptivity.

PMID- 24877151
TI  - Prospective analysis of 18F-FDG PET/CT predictive value in patients with low
      rectal cancer treated with neoadjuvant chemoradiotherapy and conservative
      surgery.
AB  - This study prospectively assessed (18)F-FDG PET/CT in predicting the response of
      locally advanced low rectal cancer (LRC) to neoadjuvant chemoradiation (nCRT).
      METHODS: 56 patients treated with chemoradiation underwent two (18)F-FDG PET/CT
      scans (baseline and 5-6 weeks post-nCRT). (18)F-FDG uptake (SUVmax and SUVmean)
      and differences between baseline (SUV1) and post-nCRT (SUV2) scans (DeltaSUV and
      RI%) were evaluated. Results were related to the Mandard's TRG and (y)pTNM.
      RESULTS: (18)F-FDG PET/CT sensitivity, specificity, accuracy, PPV and NPV
      resulted in 88.6%, 66.7%, 83.92%, 90.7%, and 61.5%. SUV2 resulted in better than
      SUV1 to predict nCRT response by TRG, with no significant statistical difference
      between the SUVmax2 and SUVmean2 AUC (0.737 versus 0.736; P = 0.928). The same
      applies to the (y)pTNM (0.798 versus 0.782; P = 0.192). In relation to the TRG,
      RI values had a higher AUC than DeltaSUV, with no significant difference between
      RImax and RImean (0.672 versus 0.695; P = 0.292). The same applied to the (y)pTNM
      (0.742 versus 0.741; P = 0.940). In both cases DeltaSUV does not appear to be a
      good predictive tool. Logistic regression confirmed the better predictive role of
      SUVmax2 for the (y)pTNM (odds ratio = 1.58) and SUVmean2 for the TRG (odds ratio
      = 1.87). CONCLUSIONS: (18)F-FDG PET/CT can evaluate response to nCRT in LRC, even
      if more studies are required to define the most significant parameter for
      predicting pathologic tumor changes.

PMID- 24877152
TI  - Understanding the process of fibrosis in Duchenne muscular dystrophy.
AB  - Fibrosis is the aberrant deposition of extracellular matrix (ECM) components
      during tissue healing leading to loss of its architecture and function. Fibrotic
      diseases are often associated with chronic pathologies and occur in a large
      variety of vital organs and tissues, including skeletal muscle. In human muscle,
      fibrosis is most readily associated with the severe muscle wasting disorder
      Duchenne muscular dystrophy (DMD), caused by loss of dystrophin gene function. In
      DMD, skeletal muscle degenerates and is infiltrated by inflammatory cells and the
      functions of the muscle stem cells (satellite cells) become impeded and
      fibrogenic cells hyperproliferate and are overactivated, leading to the
      substitution of skeletal muscle with nonfunctional fibrotic tissue. Here, we
      review new developments in our understanding of the mechanisms leading to
      fibrosis in DMD and several recent advances towards reverting it, as potential
      treatments to attenuate disease progression. 

PMID- 24877153
TI  - Naja naja karachiensis envenomation: biochemical parameters for cardiac, liver,
      and renal damage along with their neutralization by medicinal plants.
AB  - Naja naja karachiensis envenomation was found to hit more drastically heart,
      liver, and kidneys. 400 MUg/kg of venom-raised moderate serum levels of ALT (72
      +/- 4.70 U/L, 0.1 > P > 0.05), AST (157 +/- 24.24 U/L, 0.1 > P > 0.05), urea (42
      +/- 3.08 mg/dL, 0.05 > P > 0.02), creatinine (1.74 +/- 0.03 mg/dL, 0.01 > P >
      0.001), CK-MB (21 +/- 1.5 U/L, 0.05 > P > 0.02), and LDH (2064 +/- 15.98 U/L, P <
      0.001) were injected in experimental rabbits. However, lethality was enhanced
      with 800 MUg/kg of venom in terms of significant release of ALT (86 +/- 5.0 U/L,
      0.05 > P > 0.02), AST (251 +/- 18.2 U/L, 0.01 > P > 0.001), urea (57.6 +/- 3.84
      mg/dL, 0.02 > P > 0.01), creatinine (2.1 +/- 0.10 mg/dL, 0.02 > P > 0.01), CK-MB
      (77 +/- 11.22 U/L, 0.05 > P > 0.02), and LDH (2562 +/- 25.14 U/L, P ? 0.001).
      Among twenty-eight tested medicinal plant extracts, only Stenolobium stans (L.)
      Seem was found the best antivenom (P > 0.5) compared to the efficacy of standard
      antidote (ALT = 52.5 +/- 3.51 U/L, AST = 69.5 +/- 18.55 U/L, urea = 31.5 +/- 0.50
      mg/dL, creatinine = 1.08 +/- 0.02 mg/dL, CK-MB = 09 +/- 0.85 U/L, and LDH = 763
      +/- 6.01 U/L). Other plant extracts were proved less beneficial and partly
      neutralized the toxicities posed by cobra venom. However, it is essential in
      future to isolate and characterize bioactive compound(s) from Stenolobium stans
      (L.) Seem extract to overcome the complications of snake bite.

PMID- 24877155
TI  - Vertical ridge augmentation of the atrophic posterior mandible with sandwich
      technique: bone block from the chin area versus corticocancellous bone block
      allograft--clinical and histological prospective randomized controlled study.
AB  - The aim of the present study is to compare the histological aspects of bone
      formation in atrophic posterior mandibles augmented by autologous bone block from
      chin area with corticocancellous bone block allograft used as inlays with the
      sandwich technique. MATERIALS AND METHODS: Sixteen patients with bilateral
      partial edentulism in the posterior mandible were selected. The residual bone
      height, preliminarily measured by computed tomography scans, ranged between 5 and
      7 mm from the inferior alveolar nerve. All patients required regeneration
      procedure with autologous bone block from chin area (control group) versus bone
      block allograft Puros (Zimmer Dental, 1900 Aston Avenue, Carlsbad, CA, USA) (test
      group). Histological and histomorphometric samples were collected at the time of
      implant positioning in order to analyze the percentage of newly formed bone, the
      residual graft material, and marrow spaces/soft tissue. RESULTS: No statistically
      significant differences between the two groups were found regarding the
      percentage of newly formed bone. The percentage of residual grafted material was
      significantly higher in the test group, whilst the percentage of marrow spaces
      was higher in control group. CONCLUSIONS: In conclusion, both procedures
      supported good results, although the use of bone blocks allograft was less
      invasive and preferable than harvesting bone from the mental symphysis.

PMID- 24877154
TI  - Association of tissue mRNA and serum antigen levels of members of the urokinase
      type plasminogen activator system with clinical and prognostic parameters in
      prostate cancer.
AB  - The objective was to determine the mRNA expression and protein levels of uPA
      system components in tissue specimens and serum samples, respectively, from
      prostate cancer (PCa) patients and to assess their association with
      clinicopathological parameters and overall survival (OS). The mRNA expression
      levels of uPA, its receptor (uPAR), and its inhibitor type 1 (PAI-1) were
      analyzed in corresponding malignant and adjacent nonmalignant tissue specimens
      from 132 PCa patients by quantitative PCR. Preoperative serum samples from 81 PCa
      patients were analyzed for antigen levels of uPA system members by ELISA. RNA
      levels of uPA system components displayed significant correlations with each
      other in the tumor tissues. A significantly decreased uPA mRNA expression in PCa
      compared to the corresponding nonmalignant tissue was detected. High uPA mRNA
      level was significantly associated with a high Gleason score. Elevated
      concentration of soluble uPAR (suPAR) in serum was significantly associated with
      a poor OS of PCa patients (P = 0.022). PCa patients with high suPAR levels have a
      significantly higher risk of death (multivariate Cox's regression analysis; HR =
      7.12, P = 0.027). The association of high suPAR levels with poor survival of PCa
      patients suggests a prognostic impact of suPAR levels in serum of cancer
      patients. 

PMID- 24877156
TI  - Osteodifferentiated mesenchymal stem cells from bone marrow and adipose tissue
      express HLA-G and display immunomodulatory properties in HLA-mismatched settings:
      implications in bone repair therapy.
AB  - Mesenchymal stem cells (MSCs) are multipotent cells that can be obtained from
      several sources such as bone marrow and adipose tissue. Depending on the culture
      conditions, they can differentiate into osteoblasts, chondroblasts, adipocytes,
      or neurons. In this regard, they constitute promising candidates for cell-based
      therapy aimed at repairing damaged tissues. In addition, MSCs display
      immunomodulatory properties through the expression of soluble factors including
      HLA-G. We here analyse both immunogenicity and immunosuppressive capacity of MSCs
      derived from bone marrow and adipose tissue before and after
      osteodifferentiation. Results show that HLA-G expression is maintained after
      osteodifferentiation and can be boosted in inflammatory conditions mimicked by
      the addition of IFN-gamma and TNF-alpha. Both MSCs and osteodifferentiated MSCs
      are hypoimmunogenic and exert immunomodulatory properties in HLA-mismatched
      settings as they suppress T cell alloproliferation in mixed lymphocyte reactions.
      Finally, addition of biomaterials that stimulate bone tissue formation did not
      modify MSC immune properties. As MSCs combine both abilities of osteoregeneration
      and immunomodulation, they may be considered as allogenic sources for the
      treatment of bone defects.

PMID- 24877158
TI  - A photoresponsive graphene oxide-C60 conjugate.
AB  - An all-carbon donor-acceptor hybrid combining graphene oxide (GO) and C60 has
      been prepared. Laser flash photolysis measurements revealed the occurrence of
      photoinduced electron transfer from the GO electron donor to the C60 electron
      acceptor in the conjugate. 

PMID- 24877159
TI  - Anthropogenic reaction parameters--the missing link between chemical intuition
      and the available chemical space.
AB  - How do skilled synthetic chemists develop good intuitive expertise? Why can we
      only access such a small amount of the available chemical space-both in terms of
      the reactions used and the chemical scaffolds we make? We argue here that these
      seemingly unrelated questions have a common root and are strongly interdependent.
      We performed a comprehensive analysis of organic reaction parameters dating back
      to 1771 and discovered that there are several anthropogenic factors that limit
      reaction parameters and thus the scope of synthetic chemistry. Nevertheless, many
      of the anthropogenic limitations such as narrow parameter space and the
      opportunity for rapid and clear feedback on the progress of reactions appear to
      be crucial for the acquisition of valid and reliable chemical intuition. In
      parallel, however, all of these same factors represent limitations for the
      exploration of available chemistry space and we argue that these are thus at
      least partly responsible for limited access to new chemistries. We advocate,
      therefore, that the present anthropogenic boundaries can be expanded by a more
      conscious exploration of "off-road" chemistry that would also extend the
      intuitive knowledge of trained chemists. 

PMID- 24877160
TI  - Application of diffusive gel-type probes for assessing redox zonation and mercury
      methylation in the Mekong Delta sediment.
AB  - The vertical profiles of PO4(3-), Mn, Fe, S(2-), Hg, and CH3Hg(+) in sediment
      pore water were investigated using DGT and DET probes in the Tien River, the
      northern branch of Vietnam's Mekong Delta. Although some of the DGT measurements
      could be lower than the actual pore water concentrations due to the depletion of
      the species, the measurements provided information for understanding redox
      zonation and Hg methylation. The gradual increases in the measured species
      concentrations with the sediment depth were observed and the diffusive fluxes of
      the species to overlying water were expected. The vertical profiles suggested
      that (1) SO4(2-) seemed to be reduced before Fe(3+), or the two electron
      acceptors were reduced simultaneously; (2) the release of PO4(3-) was more
      closely related to S(2-) than Fe release; and (3) Hg methylation was active in
      the micro-niche between the aerobic and anaerobic transition zones. The maximum
      pore water CH3Hg(+) concentrations were observed at depths just above where the
      maximum S(2-) concentrations were detected. Hence, the maximum CH3Hg(+)
      concentration was observed near surficial sediments (less than 1 cm from the
      surface) in brackish water, and at a depth of 3 cm in fresh water. The different
      vertical profiles led to a CH3Hg(+) diffusive flux eight-times greater in
      brackish than in fresh water. The present study showed that the in situ
      application of DGT and DET probes was helpful to understand coupled
      biogeochemical reactions and mercury methylation by measuring pore water redox
      species. 

PMID- 24877162
TI  - Cranial muscle development in frogs with different developmental modes: direct
      development versus biphasic development.
AB  - Normal development in anurans includes a free swimming larva that goes through
      metamorphosis to develop into the adult frog. We have investigated cranial muscle
      development and adult cranial muscle morphology in three different anuran
      species. Xenopus laevis is obligate aquatic throughout lifetime, Rana(Lithobates)
      pipiens has an aquatic larvae and a terrestrial adult form, and Eleutherodactylus
      coqui has direct developing juveniles that hatch from eggs deposited on leaves
      (terrestrial). The adult morphology shows hardly any differences between the
      investigated species. Cranial muscle development of E. coqui shows many
      similarities and only few differences to the development of Rana (Lithobates) and
      Xenopus. The differences are missing muscles of the branchial arches (which
      disappear during metamorphosis of biphasic anurans) and a few heterochronic
      changes. The development of the mandibular arch (adductor mandibulae) and hyoid
      arch (depressor mandibulae) muscles is similar to that observed in Xenopus and
      Rana (Lithobates), although the first appearance of these muscles displays a
      midmetamorphic pattern in E. coqui. We show that the mix of characters observed
      in E. coqui indicates that the larval stage is not completely lost even without a
      free swimming larval stage. Cryptic metamorphosis is the process in which
      morphological changes in the larva/embryo take place that are not as obvious as
      in normal metamorphosing anurans with a clear biphasic lifestyle. During cryptic
      metamorphosis, a normal adult frog develops, indicating that the majority of
      developmental mechanisms towards the functional adult cranial muscles are
      preserved.

PMID- 24877161
TI  - Angle sensing in magnetotaxis of Magnetospirillum magneticum AMB-1.
AB  - The mechanism of how magnetotactic bacteria navigate along the magnetic field has
      been a puzzle. Two main models disagree on whether the magnetotactic behavior
      results from passive alignment with the magnetic field or active sensing of the
      magnetic force. Here, we quantitatively studied the swimming patterns of
      Magnetospirillum magneticum AMB-1 cells to understand the origin of their
      magnetotactic behaviors. Single-cell tracking and swimming pattern analysis
      showed that the cells follow a mixed run-reverse-tumble pattern. The average run
      time decreased with the angle between the cell's moving velocity and the external
      magnetic field. For mutant cells without the methyl-accepting chemotaxis protein
      (MCP) Amb0994, such dependence disappeared and bacteria failed to align with
      magnetic field lines. This dysfunction was recovered by complementary Amb0994 on
      a plasmid. At high magnetic field (>5 mT), all strains with intact magnetosome
      chains (including the Deltaamb0994-0995 strains) showed alignment with the
      external magnetic field. These results suggested that the mechanism for
      magnetotaxis is magnetic field dependent. Due to the magnetic dipole moment of
      the cell, the external magnetic field exerts a torque on the cell. In high
      magnetic fields, this torque is large enough to overcome the random re
      orientation of the cell, and the cells align passively with the external magnetic
      field, much like a compass. In smaller (and biologically more relevant) external
      fields, the external force alone is not strong enough to align the cell
      mechanically. However, magnetotactic behaviors persist due to an active sensing
      mechanism in which the cell senses the torque by Amb0994 and actively regulates
      the flagella bias accordingly to align its orientation with the external magnetic
      field. Our results reconciled the two putative models for magnetotaxis and
      revealed a key molecular component in the underlying magneto-sensing pathway. 

PMID- 24877163
TI  - Increased clarity on the use of radiotherapy in the management of desmoplastic
      melanoma.

PMID- 24877164
TI  - [Eyelids and tear ducts].

PMID- 24877157
TI  - The role of dendritic cells in tissue-specific autoimmunity.
AB  - In this review, we explore the role of dendritic cell subsets in the development
      of tissue-specific autoimmune diseases. From the increasing list of dendritic
      cell subclasses, it is becoming clear that we are only at the beginning of
      understanding the role of these antigen presenting cells in mediating
      autoimmunity. Emerging research areas for the study of dendritic cell involvement
      in the onset and inhibition of tissue-specific autoimmunity are presented.
      Further, we compare tissue specific to systemic autoimmunity to demonstrate how
      development of dendritic cell-based therapies may be broadly applicable to both
      classes of autoimmunity. Continued development of these research areas will lead
      us closer to clinical assessment of novel immunosuppressive therapy for the
      reversal and prevention of tissue-specific autoimmunity. Through description of
      dendritic cell functions in the modulation of tissue-specific autoimmunity, we
      hope to stimulate a greater appreciation and understanding of the role dendritic
      cells play in the development and treatment of autoimmunity. 

PMID- 24877165
TI  - Lucio Parenzan: an appreciation.

PMID- 24877166
TI  - Obituary of Lucio Parenzan.

PMID- 24877168
TI  - The state of mind in the Anatolian Journal of Cardiology.

PMID- 24877167
TI  - Multi-institutional, randomized, double-blind, placebo-controlled trial to assess
      the efficacy of a mucoadhesive hydrogel (MuGard) in mitigating oral mucositis
      symptoms in patients being treated with chemoradiation therapy for cancers of the
      head and neck.
AB  - BACKGROUND: The objective of this trial was to determine how a mucoadhesive
      hydrogel (MuGard), a marketed medical device, would fare when tested with the
      strictness of a conventional multi-institutional, double-blind, randomized,
      placebo-controlled study format. METHODS: A total of 120 subjects planned to
      receive chemoradiation therapy (CRT) for treatment of head and neck cancers were
      randomized to receive either MuGard or sham control rinse (SC) during CRT.
      Subjects completed the validated Oral Mucositis Daily Questionnaire. Weight,
      opiate use, and World Health Organization (WHO) oral mucositis (OM) scores were
      recorded. Subjects who dosed at least once daily during the first 2.5 weeks of
      CRT were included in the efficacy analysis. RESULTS: Of 120 subjects enrolled, 78
      (SC, N=41; MuGard, N=37) were eligible for efficacy analysis. Both cohorts were
      similar in demographics, baseline characteristics, primary tumor type, and
      planned CRT regimen. MuGard effectively mitigated OM symptoms as reflected by
      area under the curve of daily patient-reported oral soreness (P=.034) and WHO
      scores on the last day of radiation therapy (P=.038). MuGard was also associated
      with nonsignificant trends related to therapeutic benefit including opioid use
      duration, and OM scores (WHO criteria) at CRT week 4. Rinse compliance was
      identical between cohorts. No significant adverse events were reported, and the
      adverse event incidence was similar between cohorts. CONCLUSIONS: Testing MuGard,
      a rinse marketed as a device, in a standard clinical trial format demonstrated
      its superiority to SC in mitigating OM symptoms, delaying OM progression, and its
      safety and tolerability.

PMID- 24877169
TI  - Mental health, transactions of the Epidemiological Society of London and
      Berkson's bias.

PMID- 24877170
TI  - Transitions.

PMID- 24877171
TI  - An atypical variant of phacomatosis pigmentokeratotica: verrucous epidermal
      nevus, speckled lentiginous nevus, and Spitz nevus associated with scoliosis.

PMID- 24877172
TI  - Remarks on the outbreak of cholera in Broad  Street, Golden Square, London, in
      1854.

PMID- 24877173
TI  - Proposed classification of longitudinal melanonychia based on clinical and
      dermoscopic criteria.
AB  - BACKGROUND: For longitudinal melanonychia, clinical and dermoscopic criteria for
      differentiating malignant melanoma in situ from benign nevus/lentigo/functional
      melanonychia have not been fully established. OBJECTIVE: To propose a clinical
      classification of longitudinal melanonychia that is useful in judging the need
      for follow-up. METHODS: A total of 137 patients with longitudinal melanonychia
      referred to our outpatient clinic in the most recent eight years were included.
      The mean and median lengths of follow-up for patients were 5.0 and 5.5 years,
      respectively. We classified the 137 lesions into three types by clinical and
      dermoscopic features of the nail and periungual skin, including Hutchinson sign,
      variation of color, and borders in the pigmentation band. We observed type I and
      II lesions with dermoscopy every six months and three months, respectively.
      RESULTS: After follow-up, all 72 lesions classified as type I were thought to be
      benign nevus/lentigo/functional melanonychia. Five of the 52 lesions classified
      as type II showed enlargement during follow-up, and biopsy was performed. Of
      these five lesions, three were diagnosed as nevus/lentigo, and the other two were
      diagnosed as malignant melanoma in situ. All 13 lesions classified as type III
      were diagnosed as malignant melanoma in situ. CONCLUSION: We can expect a type I
      lesion to be a benign nevus/lentigo/functional melanonychia and a type III lesion
      to be a malignant melanoma in situ; however, type II lesions fall in a gray zone.
      We believe this classification is useful in deciding treatment and follow-up.

PMID- 24877174
TI  - Porokeratotic eccrine ostial and dermal duct nevus with linear verrucous
      epidermal nevus: an unusual association.

PMID- 24877175
TI  - Re: Peyronie's disease plaque calcification--prevalence, time to identification,
      and development of a new grading classification.

PMID- 24877177
TI  - The global online sexuality survey (GOSS): the United States of America in 2011
      chapter III--premature ejaculation among English-speaking male Internet users.

PMID- 24877176
TI  - Medical research: Gene-therapy reboot.

PMID- 24877178
TI  - A rare case of rectovaginal fistula following consensual vaginal intercourse.
AB  - INTRODUCTION: Postcoital nonobstetric vaginal lacerations due to consensual
      sexual act are generally minute mucosal tears. In some cases, the vaginal mucosa
      is lacerated deeper and the bleeding may require suturing of opened vessel ends
      or even transfusion. AIM: The aim of this case report is to present a rare case
      of acute fistula formation by penile penetration through the full thickness of
      the rectovaginal wall after consensual vaginal intercourse and to its management
      in emergency settings. METHODS: We report a rare case of isolated rectovaginal
      laceration sparing anal sphincters and perineumin a 24-year-old woman following
      her second consensual vaginal intercourse with her new partner. Speculum
      examination demonstrated a 4 cm laceration on the left posterior vaginal wall
      forming a fistula between the rectum and vagina, 2 cm above the hymenal ring and
      not extending to the posterior fornix or perineum. Three layer suturing of
      rectal, vaginal mucosa, and rectovaginal septum was enough to treat the acute
      fistula in this case. RESULTS: After 2 months follow-up, we observed the complete
      healing of the rectovaginal laceration with no fistula formation and the patient
      resumed her sexual activity. Long term follow-up of patients is necessary to
      observe complete healing and to ensure the absence of a chronic fistula
      formation. CONCLUSION: Simple suturing of rectal and vaginal mucosa, appropriate
      antiseptic precautions, and antibiotic coverage are enough to treat acutely
      formed low rectovaginal fistulas resulting from coitus. Decision to form
      colostomy and diversion of feces in the repair of such injuries should be taken
      cautiously.

PMID- 24877179
TI  - Nebivolol potentiates the efficacy of PDE5 inhibitors to relax corpus cavernosum
      and penile arteries from diabetic patients by enhancing the NO/cGMP pathway.
AB  - INTRODUCTION: The efficacy of oral pharmacotherapy for erectile dysfunction (ED)
      (i.e., type 5 phosphodiesterase[PDE5] inhibitors) is significantly reduced in
      diabetic patients. Nebivolol is a selective beta1-blocker used for treatinghy
      pertension that has been shown to increase the efficacy of sildenafil to reverse
      ED in diabetic rats. AIM: To evaluate the effects of nebivolol on the efficacy of
      the PDE5 inhibitors, sildenafil, tadalafil, and vardenafil to relax human corpus
      cavernosum (HCC) and vasodilate human penile resistance arteries (HPRA) from
      diabetic patients with ED (DMED). The influence of nebivolol on the capacity of
      these three PDE5 inhibitors to stimulate cyclic guanosine monophosphate (cGMP)
      production in HCC was also evaluated. METHODS: HCC and HPRA were obtained from
      organ donors without ED (NEND; n = 18) or patients with diabetes undergoing
      penile prosthesis implantation (DMED; n = 19). Relaxations of HCC strips and HPRA
      to sildenafil,tadalafil, and vardenafil were evaluated in organ chambers and wire
      myographs. cGMP content in HCC was determined by ether extraction and
      quantification by ELISA. MAIN OUTCOME MEASURES: Effects of nebivolol on PDE5
      inhibitor-induced relaxation of HCC, vasodilation ofHPRA and cGMP accumulation in
      HCC. RESULTS: Treatment with nebivolol (1 MUM) significantly potentiated
      sildenafil-, tadalafil- and vardenafil-induced relaxations of HCC and
      vasodilations of HPRA from both NEND and DMED. Enhancement of relaxant capacity
      by nebivolol resulted in reversion of the impairment of PDE5 inhibition-induced
      responses in DMED and it was accompanied by enhancing the ability of PDE5
      inhibitors to increase cGMP in HCC restoring reduced cGMP levelsin HCC from DMED.
      CONCLUSIONS: Nebivolol potentiated the capacity of PDE5 inhibitors to relax
      vascular structures of erectile tissue from diabetic patients by enhancing the
      nitric oxide (NO)/cGMP pathway in these tissues. These effects suggest a
      potential therapeutic utility of nebivolol as an adjunct to PDE5 inhibitors for
      the treatment of ED associated with diabetes.

PMID- 24877180
TI  - Policy: An intergovernmental panel on antimicrobial resistance.

PMID- 24877181
TI  - A phase I study in patients with solid or hematologic malignancies of the dose
      proportionality of subcutaneous Azacitidine and its pharmacokinetics in patients
      with severe renal impairment.
AB  - STUDY OBJECTIVE: To assess the dose proportionality of azacitidine
      pharmacokinetics (PK) after single subcutaneous (SC) doses of 25-100 mg/m2, and
      determine the effect of renal impairment on PK after single and multiple 75 mg/m2
      SC azacitidine doses. DESIGN: Multicenter, phase I, open-label, parallel group
      study. SETTING: Community clinics and major academic centers. PATIENTS: Twenty
      seven patients with solid or hematologic malignancies. INTERVENTIONS: Part 1
      evaluated azacitidine dose proportionality in patients with normal renal function
      randomized to single 25, 50, 75, or 100 mg/m2 SC doses. The 75 mg/m2 dosing group
      received 4 additional days of SC azacitidine. In Part 2, patients with severe
      renal impairment (creatinine clearance < 30 ml/min/1.73 m2 Cockcroft-Gault
      adjusted) received azacitidine 75 mg/m2 for 5 consecutive days. MEASUREMENTS AND
      MAIN RESULTS: PK parameters were determined using noncompartmental methods. In
      patients with normal renal function (n=21), azacitidine area under the plasma
      time curve (AUC0-infinity) and maximum observed plasma concentration (Cmax) were
      dose proportional within the 25-100 mg/m2 range. Concentration versus time
      profiles after single and multiple azacitidine 75 mg/m2 doses were similar in
      shape for patients with normal (n=6) or impaired renal function (n=6), with
      higher mean concentrations in the latter group. Higher mean exposures (AUC0
      infinity and Cmax) in renally impaired patients were observed; however,
      individual exposure values were, with few exceptions, within the same range in
      both groups. No drug accumulation after multiple doses was observed in either
      group. Terminal half-life and time to maximum plasma concentration were
      comparable between groups. Azacitidine tolerability was similar in patients with
      normal or impaired renal function. CONCLUSION: Azacitidine is dose proportional
      over the 25-100 mg/m2 dosing range. Overall, renal impairment had no important
      effect on azacitidine PK. Therefore, no initial azacitidine dose adjustment in
      patients with renal impairment is required.

PMID- 24877182
TI  - Health care: Bring microbial sequencing to hospitals.

PMID- 24877183
TI  - A three-step plan for antibiotics.

PMID- 24877184
TI  - Clean break.

PMID- 24877185
TI  - Sigmoidal maximal effect modeling of low-density lipoprotein cholesterol
      concentration and annual incidence of coronary heart disease events in secondary
      prevention trials.
AB  - STUDY OBJECTIVES: To evaluate the relationship between low-density lipoprotein
      cholesterol (LDL-C) concentration and the annual incidence of combined coronary
      heart disease (CHD) events-death or nonfatal myocardial infarction (NFMI)-by
      using sigmoidal maximal effect (sEmax) modeling of published data in various
      populations at risk for CHD events, and to use the best performing sEmax model
      generated to calculate the number needed to treat (NNT) to prevent a single CHD
      death or NFMI event across a range of LDL-C concentrations. DESIGN: Literature
      based modeling analysis. PATIENTS: A total of 95,955 patients from 22 published
      cardiovascular secondary prevention trials. MEASUREMENTS AND MAIN RESULTS: Four
      distinct sEmax models were created based on intervention approach and CHD event
      risk for each trial population. Model outputs included the following: Emax
      (maximum CHD death/NFMI rate), E0 (minimum CHD death/NFMI rate), and fit
      parameters. The best-fitting sEmax model was compared with linear, log-linear,
      and logit models, and it was used for calculation of annualized NNT to prevent
      one CHD death or NFMI event with statins. The best fitting sEmax model was
      constructed from nine statin intervention trials in 60,483 clinically stable
      patients with CHD or CHD risk equivalents (Emax = 4.84%/year [95% confidence
      interval (CI) 4.11-5.41%/year], E0 = 1.24%/year [95% CI 0.64-1.83%/year]) and was
      superior to linear, log-linear, and logit models. Reduction of CHD death/NFMI
      incidence diminished at an LDL-C level near 90 mg/dl and became near static at an
      LDL-C level of 60-70 mg/dl. Annual NNT for LDL-C reduction from a baseline of 130
      100 mg/dl, 90, and 70 mg/dl was 129, 104, and 83, respectively, and from a
      baseline of 100-70 mg/dl was 232. CONCLUSION: An sEmax model fully characterized
      the relationship between LDL-C concentration and incidence of CHD death or NFMI
      in a high-risk population receiving statins, with diminishing event reduction at
      an LDL-C level less than 90 mg/dl, and limited projected event reduction beyond
      an LDL-C level of ~60-70 mg/dl. As baseline LDL-C level declines, the NNT sharply
      increases.

PMID- 24877186
TI  - Evaluation of preventive cardiovascular pharmacotherapy after coronary artery
      bypass graft surgery.
AB  - STUDY OBJECTIVE: To determine the rate of secondary prevention cardiovascular
      drug utilization in a cohort of patients who underwent coronary artery bypass
      graft (CABG) surgery-including specific drugs and their dosages, drug adherence,
      and assessment of targeted therapy--from admission to 1 year after CABG surgery.
      DESIGN: Retrospective analysis. SETTING: Cardiovascular quaternary care medical
      center in Edmonton, Canada. PATIENTS: The entire cohort consisted of 1031 adults
      who underwent CABG surgery between January 2009 and March 2010; a randomly
      selected subset of 151 patients was used to evaluate medication use and target
      directed therapy at 1 year after CABG surgery. MEASUREMENTS AND MAIN RESULTS:
      Utilization rates of aspirin, beta-blockers, statins, and angiotensin-converting
      enzyme inhibitors or angiotensin II receptor blockers (ACEIs/ARBs) on admission
      and at discharge were determined for the entire cohort by using data from a large
      clinical patient registry. The proportion of patients discharged receiving all
      four classes of medications was 35%. Individual utilization rates for aspirin,
      beta-blockers, and statins were 96%, 94%, and 95%, respectively; use of
      ACEIs/ARBs was lowest at 42%. In the 1-year post-CABG surgery substudy,
      medication use and target-directed therapy at 1 year after CABG surgery were
      evaluated by using community pharmacy and electronic health records. The
      proportion of patients receiving all four classes of medications at 1 year was
      48%. Individual utilization rates for aspirin, beta-blockers, statins, and
      ACEIs/ARBs were 95%, 84%, 84%, and 65%, respectively. Medication adherence,
      assessed by the medication possession ratio, for beta-blockers, statins, and
      angiotensin-modulating agents at 1 year exceeded 0.85, thereby demonstrating high
      adherence. Evaluation of target-directed treatment of dyslipidemia and diabetes
      mellitus demonstrated suboptimal control, with only 66% and 54% of patients,
      respectively, achieving the recommended therapeutic targets. CONCLUSION: The
      utilization rate for patients receiving all four classes of secondary prevention
      cardiovascular medications was 35% at discharge and 48% at 1 year after CABG
      surgery. These rates were primarily limited by the low utilization of angiotensin
      modulating agents, although their rate improved by 22% from discharge.
      Utilization rates, however, were high for aspirin, beta-blockers, and statins
      both at discharge and 1 year after surgery. Opportunities remain to further
      optimize secondary prevention cardiovascular pharmacotherapy in patients who
      undergo CABG surgery, either while in the hospital or immediately subsequent to
      discharge.

PMID- 24877187
TI  - Improving adherence to oral cancer therapy in clinical practice.
AB  - Adherence to oral chemotherapy regimens maximizes their effectiveness and
      minimizes any potential toxicities. Factors specifically related to the
      treatment, patient, and health care provider may influence medication adherence.
      Treatment-related factors include the complexity of the regimen, the cost of
      therapy, the possibility of side effects, and the delay in treatment benefits.
      Meanwhile, patients may not have an adequate support system or an understanding
      of the need for the medication, and providers may not fully succeed in
      communicating the importance of adherence and the types of side effects that may
      occur. Nonadherence may lead to an increased risk of toxicity, decreased
      effectiveness, and increased utilization of health care resources. Although
      various methods for measuring adherence are available, self-reporting is the most
      widely used. Studies describing adherence in a broad range of cancers are
      reviewed. Treatment of chronic myeloid leukemia has been revolutionized by the
      development of oral tyrosine kinase inhibitors that are highly effective in
      managing the disease when taken consistently. However, nonadherence is relatively
      common and can lead to reduced rates of response and increased medical costs.
      Similar effects of nonadherence on outcome and cost have also been observed in
      patients with various other hematologic malignancies and solid tumors.
      Interventions to improve adherence to oral chemotherapy regimens include
      communication about the importance of adherence and the potential consequences of
      nonadherence, simplification of the patient's medication schedule (if possible),
      and inclusion of a caregiver or family member in the conversation. Written
      materials should always be provided to accompany verbal instructions. This review
      summarizes factors influencing medication adherence, impact of nonadherence on
      patient outcomes, methods for measuring adherence, previous studies of
      nonadherence in patients with cancer, common barriers to access, and
      interventions to improve adherence in the community setting.

PMID- 24877188
TI  - Minimum qualifications for clinical pharmacy practice faculty.
AB  - The American College of Clinical Pharmacy 2013 Educational Affairs Committee was
      charged with developing recommendations for the minimum qualifications required
      for clinical pharmacy practice faculty in United States colleges and schools of
      pharmacy with respect to education, postgraduate training, board certification,
      and other experiences. From a review of the literature, the committee recommends
      that clinical pharmacy practice faculty possess the following minimum
      qualifications, noting that, for some positions, additional qualifications may be
      necessary. Clinical pharmacy practice faculty should possess the Doctor of
      Pharmacy degree from an Accreditation Council for Pharmacy Education-accredited
      institution. In addition, faculty should have completed a postgraduate year one
      (PGY1) residency or possess at least 3 years of direct patient care experience.
      Faculty who practice in identified areas of pharmacotherapy specialization, as
      identified by American Society of Health-System Pharmacists postgraduate year two
      (PGY2) residency guidelines, should have completed a PGY2 residency in that area
      of specialty practice. Alternatively, faculty should have completed a minimum of
      a PGY1 residency and 1 additional year of practice, with at least 50% of time
      spent in their area of specialization, which is documented in a portfolio, or 4
      years of direct patient care in their area of specialization, which is documented
      in a portfolio. Fellowship training or a graduate degree (e.g., Ph.D.) should be
      required for research-intensive clinical faculty positions. All faculty should
      obtain structured teaching experience during or after postgraduate training,
      preferably through a formal teaching certificate program or through activities
      documented in a teaching portfolio. A baseline record of scholarship should be
      obtained before hire as clinical pharmacy practice faculty through exposure in
      postgraduate programs or previous employment. Faculty should be board certified
      before hire or attain board certification within 2 years of hire through the
      Board of Pharmacy Specialties (BPS) or, if appropriate for the practice area,
      through a nonBPS-certifying agency. If no certification exists in the area of
      specialty, the faculty member should develop a portfolio with evidence of
      excellence in clinical practice, teaching, and scholarship.

PMID- 24877189
TI  - Innovation in clinical pharmacy practice and opportunities for academic--practice
      partnership.
AB  - Clinical pharmacy has a rich history of advancing practice through innovation.
      These innovations helped to mold clinical pharmacy into a patient-centered
      discipline recognized for its contributions to improving medication therapy
      outcomes. However, innovations in clinical pharmacy practice have now waned. In
      our view, the growth of academic-practice partnerships could reverse this trend
      and stimulate innovation among the next generation of pioneering clinical
      pharmacists. Although collaboration facilitates innovation,academic institutions
      and health care systems/organizations are not taking full advantage of this
      opportunity. The academic-practice partnership can be optimized by making both
      partners accountable for the desired outcomes of their collaboration, fostering
      symbiotic relationships that promote value-added clinical pharmacy services and
      emphasizing continuous quality improvement in the delivery of these services.
      Optimizing academic-practice collaboration on a broader scale requires both
      partners to adopt a culture that provides for dedicated time to pursue
      innovation, establishes mechanisms to incubate ideas, recognizes where motivation
      and vision align, and supports the purpose of the partnership. With appropriate
      leadership and support, a shift in current professional education and training
      practices, and a commitment to cultivate future innovators, the academic-practice
      partnership can develop new and innovative practice advancements that will
      improve patient outcomes.

PMID- 24877191
TI  - Author's reply.

PMID- 24877190
TI  - Author's reply: To PMID 23241338.

PMID- 24877192
TI  - Author's reply: To PMID 23395706.

PMID- 24877194
TI  - Author's reply.

PMID- 24877193
TI  - Author's reply: To PMID 23886900.

PMID- 24877196
TI  - Subcutaneous histiocytoid Sweet's syndrome in a patient with myelodysplastic
      syndrome and acute myeloblastic leukemia.
AB  - Subcutaneous histiocytoid Sweet's syndrome is a rare variant of histiocytoid
      Sweet's syndrome (SS). We present a 68-year-old woman with subcutaneous
      histiocytoid SS in association with refractory myelodysplastic syndrome
      transformed to acute myeloblastic leukemia (AML), status post induction
      chemotherapy and with persistent blasts (50%) in the bone marrow and blood,
      accompanied with neutropenia. The patient presented to the emergency room with
      fever and altered mental status. Clinical examination revealed approximately 20
      scattered 0.5-2 cm, pink to pink-purple non-tender firm nodules on the legs and
      left arm. The differential diagnosis included Sweet's syndrome (deep), leukemia
      cutis, infection, polyarteritis nodosa and erythema nodosum. Histopathologic
      examination of a biopsy from the left arm revealed a nodular infiltrate of
      neutrophils and histiocytoid mononuclear cells solely in the lobular compartment
      of the subcutaneous fat with focal areas of necrosis. Most cells in the
      infiltrate labeled with myeloperoxidase (MPO) including the histiocytoid cells.
      The cells were negative for CD34 and CD117. All special stains for microorganisms
      were negative. A diagnosis of subcutaneous histiocytoid SS was made. A
      subcutaneous histiocytoid SS should be suspected when a neutrophilic/histiocytoid
      panniculitis, occurring in the setting of myeloid disorders, is encountered and
      after exclusion of an infectious process and leukemia cutis.

PMID- 24877195
TI  - Cutaneous lymphatic malformation  characterized by swelling of digits:  a report
      of six cases.
AB  - BACKGROUND: Cutaneous lymphatic malformations represent a group of heterogeneous
      diseases. In clinical practice, some cases of cutaneous lymphatic malformation
      have been found to differ from the well-characterized entities, and are difficult
      to classify. OBJECTIVE: To report the clinical, histopathological and
      immunohistochemical characteristics of six cases of lymphatic malformation
      characterized by swelling of the digits. METHODS: Six patients with swelling of
      the digits were included in this study. Histopathological examination and
      immunohistochemical staining of CD31, D2-40, Prox1, Wilms tumor 1 (WT-1) and
      human herpesvirus-8 (HHV-8) were performed for all cases. RESULTS: All cases were
      congenital lesions and presented as swelling of single or multiple digits.
      Histopathologically, the lesions showed proliferation of small-to-medium-sized
      vessels in the dermis and subcutaneous tissue. These abnormal vessels were
      positive for CD31, D2-40 and Prox1, and negative for WT-1 and HHV-8. CONCLUSION:
      The six cases reported herein represent a specific cutaneous lymphatic
      malformation different from previously reported entities.

PMID- 24877198
TI  - Ultrasound guided epidural   catheter placement in a dog.

PMID- 24877197
TI  - Use of electrical nerve stimulation to monitor lumbosacral epidural needle
      placement in cats.
AB  - OBJECTIVE: To determine the minimal electrical threshold (MET) necessary to
      elicit muscle contraction of the pelvic limb or tail when an insulated needle is
      positioned outside (METout) and inside (METin) the lumbosacral epidural space in
      cats. STUDY DESIGN: Prospective, blinded study. ANIMALS: Twelve mixed-breed
      healthy adult cats, scheduled for a therapeutic procedure where lumbosacral
      epidural administration was indicated. METHODS: Under general anesthesia, an
      insulated needle was advanced through tissues of the lumbosacral interspace until
      its tip was thought to be just dorsal to the interarcuate ligament. An increasing
      electrical current (0.1 ms, 2 Hz) was applied through the stimulating needle in
      order to determine the MET necessary to obtain a muscle contraction of the pelvic
      limb or tail (METout), and then 0.05 mL kg-1 of iohexol was injected. The needle
      was further advanced until its tip was thought to be in the epidural space. The
      MET was determined again (METin) and 0.2 mL kg-1 of iohexol was injected. The
      cats were maintained in sternal position. Contrast medium spread was determined
      through lateral radiographic projections. RESULTS: The radiographic study
      confirmed the correct needle placement dorsal to the interarcuate ligament in all
      cats. When the needle was placed ventrally to the interarcuate ligament, iohexol
      was injected epidurally in ten and intrathecally in two cats. The METout and
      METin was 1.76 +/- 0.34 mA and 0.34 +/- 0.07 mA, respectively (p < 0.0001).
      CONCLUSION AND CLINICAL RELEVANCE: Nerve stimulation can be employed as a tool to
      determine penetration of the interarcuate ligament but not the piercing of the
      dura mater at the lumbosacral space in cats.

PMID- 24877199
TI  - Regulation of T-lymphocyte motility, adhesion and de-adhesion by  a cell surface
      mechanism directed by low density lipoprotein  receptor-related protein 1 and
      endogenous thrombospondin-1.
AB  - T lymphocytes are highly motile and constantly reposition themselves between a
      free-floating vascular state, transient adhesion and migration in tissues. The
      regulation behind this unique dynamic behaviour remains unclear. Here we show
      that T cells have a cell surface mechanism for integrated regulation of motility
      and adhesion and that integrin ligands and CXCL12/SDF-1 influence motility and
      adhesion through this mechanism. Targeting cell surface-expressed low-density
      lipoprotein receptor-related protein 1 (LRP1) with an antibody, or blocking
      transport of LRP1 to the cell surface, perturbed the cell surface distribution of
      endogenous thrombospondin-1 (TSP-1) while inhibiting motility and potentiating
      cytoplasmic spreading on intercellular adhesion molecule 1 (ICAM-1) and
      fibronectin. Integrin ligands and CXCL12 stimulated motility and enhanced cell
      surface expression of LRP1, intact TSP-1 and a 130,000 MW TSP-1 fragment while
      preventing formation of a de-adhesion-coupled 110 000 MW TSP-1 fragment. The
      appearance of the 130 000 MW TSP-1 fragment was inhibited by the antibody that
      targeted LRP1 expression, inhibited motility and enhanced spreading. The TSP-1
      binding site in the LRP1-associated protein, calreticulin, stimulated adhesion to
      ICAM-1 through intact TSP-1 and CD47. Shear flow enhanced cell surface expression
      of intact TSP-1. Hence, chemokines and integrin ligands up-regulate a dominant
      motogenic pathway through LRP1 and TSP-1 cleavage and activate an associated
      adhesion pathway through the LRP1-calreticulin complex, intact TSP-1 and CD47.
      This regulation of T-cell motility and adhesion makes pro-adhesive stimuli favour
      motile responses, which may explain why T cells prioritize movement before
      permanent adhesion.

PMID- 24877200
TI  - Educational and vocational outcomes of adults with childhood- and adult-onset
      systemic lupus erythematosus: nine years of followup.
AB  - OBJECTIVE: To compare educational and vocational outcomes among adults with
      childhood-onset systemic lupus erythematosus (SLE) and adult-onset SLE. METHODS:
      We used data derived from the 2002-2010 cycles of the Lupus Outcomes Study, a
      longitudinal cohort of 1,204 adult subjects with SLE. Subjects ages 18-60 years
      living in the US (n = 929) were included in the analysis and were classified as
      childhood-onset SLE if age at diagnosis was <18 years (n = 115). Logistic
      regression was used to assess the unadjusted and adjusted effect of childhood
      onset SLE, sex, race/ethnicity, baseline age, urban or rural location, and US
      region on the likelihood of completing a bachelor's degree. Generalized
      estimating equations were used to assess the effect of childhood-onset SLE,
      demographics, education, and disease-related factors on the odds of employment,
      accounting for multiple observations over the study period. RESULTS: Subjects
      with childhood-onset SLE were on average younger (mean +/- SD 29 +/- 10 years
      versus 44 +/- 9 years), with longer disease duration (mean +/- SD 15 +/- 10 years
      versus 11 +/- 8 years). Subjects with adult-onset SLE and childhood-onset SLE
      subjects were equally likely to complete a bachelor's degree. However, subjects
      with childhood-onset SLE were significantly less likely to be employed,
      independent of demographic and disease characteristics (odds ratio 0.62, 95%
      confidence interval 0.42-0.91). CONCLUSION: While subjects with SLE are just as
      likely as those with adult-onset SLE to complete college education, childhood
      onset SLE significantly increases the risk of not working in adulthood, even when
      controlling for disease and demographic factors. Exploring reasons for low rates
      of employment and providing vocational support may be important to maximize long
      term functional outcomes in patients with childhood-onset SLE.

PMID- 24877203
TI  - Ebola haemorrhagic fever in west Africa.

PMID- 24877202
TI  - Short wavelength-sensitive cones and the processing of   their signals.

PMID- 24877204
TI  - FDA action on animal antibiotics could still have loopholes.

PMID- 24877205
TI  - Labour complications. Life-threatening complications 'double' in Scotland.

PMID- 24877201
TI  - Cardiovascular risk factors in women with primary Sjogren's syndrome: United
      Kingdom primary Sjogren's syndrome registry results.
AB  - OBJECTIVE: To determine the prevalence of traditional cardiovascular risk factors
      using established definitions in a large cohort of clinically well-characterized
      primary Sjogren's syndrome (SS) patients and to compare them to healthy controls.
      METHODS: Data on cardiovascular risk factors in primary SS patients and controls
      were collected prospectively using a standardized pro forma. Cardiovascular risk
      factors were defined according to established definitions. The prevalence of
      cardiovascular risk factors in the primary SS group was determined and compared
      to that in the control group. RESULTS: Primary SS patients had a higher
      prevalence of hypertension (28-50% versus 15.5-25.6%; P < 0.01) and
      hypertriglyceridemia (21% versus 9.5%; P = 0.002) than age- and sex-matched
      healthy controls. Furthermore, a significant percentage (56%) of hypertensive
      patients expected to be on antihypertensive treatment according to best practice
      was not receiving it. CONCLUSION: Primary SS patients are more than 2 times more
      likely to experience hypertension and hypertriglyceridemia than age- and sex
      matched healthy controls. Additionally, hypertension is underdiagnosed and
      suboptimally treated in primary SS.

PMID- 24877206
TI  - Clamping update to be delivered.

PMID- 24877207
TI  - Are you involved?

PMID- 24877208
TI  - In an MSW's shoes.

PMID- 24877209
TI  - The next generation.

PMID- 24877210
TI  - The health of healthcare, Part IV: Standing before the court.
AB  - In 2012, when the U.S. Supreme Court upheld Obamacare, the law had not been
      implemented. No one was directly affected by the Patient Protection and
      Affordable Health Care Act until January 2014. After that time, if individuals
      can show proof of harm caused by Obamacare, they will have legal "standing" and
      can sue the federal government.

PMID- 24877211
TI  - Daily phosphodiesterase type 5 inhibitor therapy: a new treatment option for
      prostatitis/prostatodynia?

PMID- 24877212
TI  - Providing systematic detailed information on medication upon hospital discharge
      as an important step towards improved transitional care.
AB  - WHAT IS KNOWN AND OBJECTIVE: Good communication between hospital and primary care
      physicians (PCPs) is important for the continuity of patient care in the
      transition phase following hospital treatment. Drug-related problems and
      medication errors may occur at that interface. Discharge letters often lack a
      structured medication report at the end and therefore may not provide the reasons
      for medication changes, resulting in low adherence rates. The objectives were to
      develop a structured medication report as part of the discharge letter, to
      evaluate the impact of the medication report in ischaemic stroke patients and to
      identify the most important issues in the transitional care process of stroke
      patients. METHODS: First, a structured medication report was developed.
      Thereafter, the impact of this new medication report on clinical practice was
      evaluated with an open, prospective, interventional two-phase study conducted at
      the Klinikum Fulda gAG (Germany), which included patients with ischaemic stroke
      and >2 drugs in the discharge medication. In the control group (CG), the
      neurologist included the current medication in the discharge letter. In the
      intervention group (IG), the clinical pharmacist added the detailed information
      to a medication report. To evaluate adherence to discharge medication, the PCP
      was interviewed 3 months after hospital discharge about the medication. Adherence
      was measured with respect to the entire medication regimen, antithrombotic and
      cholesterol-lowering drugs and discontinued medication. The most important issues
      in the transitional care for patients with ischaemic stroke were identified on
      the basis of the secondary stroke prevention and cardiovascular risk factors.
      RESULTS AND DISCUSSION: Overall, 312 patients were enrolled in the study with 156
      patients in each group. By providing detailed information in the newly developed
      discharge letter, adherence increased significantly from 83.3% (CG) to 90.9% (IG;
      P = 0.01). Significant differences between the CG and IG were found with regard
      to adherence to both antithrombotic drugs [83.8% CG vs. 91.9% IG (P = 0.033)] and
      statin therapy [69.8% CG vs. 87.7% IG (P < 0.001)]. WHAT IS NEW AND CONCLUSION:
      The use of a structured medication report as part of the discharge letter leads
      to improved adherence to hospital discharge medication.

PMID- 24877213
TI  - Intersaccadic drift velocity is sensitive to short-term hypobaric hypoxia.
AB  - Hypoxia, defined as decreased availability of oxygen in the body's tissues, can
      lead to dyspnea, rapid pulse, syncope, visual dysfunction, mental disturbances
      such as delirium or euphoria, and even death. It is considered to be one of the
      most serious hazards during flight. Thus, early and objective detection of the
      physiological effects of hypoxia is critical to prevent catastrophes in civil and
      military aviation. The few studies that have addressed the effects of hypoxia on
      objective oculomotor metrics have had inconsistent results, however. Thus, the
      question of whether hypoxia modulates eye movement behavior remains open. Here we
      examined the effects of short-term hypobaric hypoxia on the velocity of saccadic
      eye movements and intersaccadic drift of Spanish Air Force pilots and flight
      engineers, compared with a control group that did not experience hypoxia.
      Saccadic velocity decreased with time-on-duty in both groups, in correlation with
      subjective fatigue. Intersaccadic drift velocity increased in the hypoxia group
      only, suggesting that acute hypoxia diminishes eye stability, independently of
      fatigue. Our results suggest that intersaccadic drift velocity could serve as a
      biomarker of acute hypoxia. These findings may also contribute to our
      understanding of the relationship between hypoxia episodes and central nervous
      system impairments.

PMID- 24877214
TI  - New atrial fibrillation classification by electrocardiogram will help general
      practitioners deliver personalized treatment.

PMID- 24877215
TI  - Shahbudin Rahimtoola: a world class cardiologist for a world class journal.

PMID- 24877216
TI  - Country of the month: Iceland.

PMID- 24877217
TI  - Boosting acute myocardial infarction treatment with stem cells.

PMID- 24877218
TI  - Reply: To PMID 24127760.

PMID- 24877219
TI  - Reflections: neurology and the humanities. Like it or not.

PMID- 24877220
TI  - Author response.

PMID- 24877221
TI  - Author response.

PMID- 24877222
TI  - Early-onset thrombocytopenia in near-term and term infants with perinatal
      asphyxia.
AB  - BACKGROUND: Neonates after perinatal asphyxia are at increased risk of
      thrombocytopenia. The correlation between perinatal asphyxia and the risk and
      severity of early-onset thrombocytopenia is not well known. OBJECTIVE: To
      estimate the incidence, severity and risk factors for early-onset
      thrombocytopenia in neonates after perinatal asphyxia. METHODS: We included all
      newborns (gestational age >= 36 weeks) admitted to our neonatal nursery due to
      perinatal asphyxia in this retrospective study. We collected platelet counts that
      were obtained within the first 48 h of life to estimate the incidence and
      severity of early-onset thrombocytopenia. RESULTS: A total number of 171 neonates
      with perinatal asphyxia were included in the study. The incidence of early-onset
      thrombocytopenia (platelet count < 150 * 109/l) was 51% (87/171). Several factors
      were associated with increased risk of early-onset thrombocytopenia, including
      prolonged prothrombin time (PT) [odds ratio (OR) 1.18, 95% confidence interval
      (CI) 1.08-1.30, P < 0.01], prolonged activated partial thromboplastin time (APTT)
      (OR 1.07, 95% CI 1.03-1.11, P < 0.01), low Apgar score at 10 min (OR 1.25, 95% CI
      1.08-1.45, P < 0.01) and high serum lactate (OR 1.12, 95% CI 1.06-1.19, P <
      0.01). After multiple logistic regression analysis, we found an independent
      association between early-onset thrombocytopenia and prolonged PT (OR 1.15, 95%
      CI 1.00-1.33, P = 0.045) and higher lactate level (OR 1.15, 95% CI 1.03-1.28, P =
      0.01). CONCLUSIONS: Early-onset thrombocytopenia occurs frequently in neonates
      after perinatal asphyxia and is independently associated with PT and lactate
      level.

PMID- 24877223
TI  - Allowing blood donation from men who had sex with men more than 5 years ago: a
      model to evaluate the impact on transfusion safety in Canada.
AB  - Canada now allows donations from men who had sex with men (MSM) if their last
      sexual contact with a man was more than 5 years ago. We modelled the impact of
      this policy on supply and safety. Approximately 4500 new donors will be added and
      assuming compliance to the new policy remains unchanged, the worst-case scenario
      predicts the introduction of one HIV-contaminated unit in the inventory every
      1072 years. This change will entail negligible additional HIV risk to recipients.
      A five-year deferral will also protect recipients against the theoretical concern
      that MSM may represent a group at higher risk of sexually transmitted, emerging
      blood borne pathogens.

PMID- 24877224
TI  - Authors' reply.

PMID- 24877225
TI  - Demographic and clinical factors associated with referrals and compliance to
      biopsy of oral and maxillofacial lesions.
AB  - BACKGROUND: The gold standard for diagnosing oral disease is tissue biopsy. Data
      regarding compliance with advised oral and maxillofacial (OMF) biopsy are scarce.
      PURPOSE: To quantify compliance and evaluate the demographics and clinical
      factors associated with referrals and compliance with OMF biopsy procedures.
      METHODS: Medical records of military personnel referred for a biopsy (RB; N =
      669) of OMF lesions over a 4-year period were studied retrospectively. These
      patients were divided into performed the biopsy (PB; N = 386) and not perform
      biopsy (NPB; N = 283) groups. Demographic and clinical features were analyzed,
      and demographics were compared to a control group of general military personnel
      (N > 100,000). RESULTS: The RB group differed from the control group regarding
      age >21 (OR = 1.681, P < 0.001) and education >12 years of schooling (OR = 1.545,
      P < 0.001). Differences between the PB and NPB groups related to the clinical
      features of the lesion but not to demographic parameters. Exophytic and suspected
      potentially malignant/malignant lesions were positively associated with higher
      compliance to biopsy (OR = 1.75, P = 0.004 and OR = 2.18, P = 0.017,
      respectively). CONCLUSION: Referrals to biopsy of OMF lesions are significantly
      influenced by age and education, whereas compliance is influenced by clinical
      features or suspected malignancy. Clinicians and health authorities should be
      aware of non-compliance, enhance awareness to biopsy as the gold standard in the
      diagnostic workup of OMF lesions, and closely monitor compliance patterns of
      patients with clinical and demographic risk factors.

PMID- 24877226
TI  - Impact--improving patient access time: arterial cannulation.
AB  - OBJECTIVES: The overall aim of the project was for an advanced critical care
      practitioner (ACCP)to develop the clinical competency of arterial
      catheterisation. The study examined the impact of the intervention being
      performed by a different staff group member. DESIGN: The project took the form of
      service development, employing a service redesign route-map. The general strategy
      was a pre/post implementation audit providing a baseline,to evaluate the change.
      SETTING: The setting was an Adult General High Dependency Unit (HDU) in a large
      Teaching Hospital. OUTCOME MEASURES: To reduce delay in arterial line insertion,
      whilst maintaining patient safety pre/post procedure, to a standard comparable to
      medical colleagues and to reduce the number of arterial punctures. RESULTS:
      Insertion complications reduced by 9% (1), with no increase in infection. Post
      procedure complications increased by 18% (2); however this occurred during
      medical team insertions, with no increase in infection during ACCP line
      insertions.Observing the whole service, both medical and ACCP insertions, mean
      length of wait, reduced from 4.3 hours to 1.2 hours: compared to less than 45
      minutes during ACCP insertions. The total number of arterial punctures for each
      patient, prior to receiving an arterial line, decreased to less than three stabs.
      CONCLUSION: All outcomes were achieved within ACCP practice, showing safe
      arterial line insertion by an ACCP in critically ill patients on HDU. Regular
      practice of the skill led to an improved technique and a reduction in delays.

PMID- 24877227
TI  - Reply to Jensen and Blackledge: Dual quantifications of intrinsically disordered
      proteins by NMR ensembles and molecular dynamics simulations.

PMID- 24877229
TI  - Chest X-ray quiz.

PMID- 24877228
TI  - Reply to Schmitt et al.: Data-filtering schemes for avoiding double-counting in
      circle sequencing.

PMID- 24877230
TI  - Concern over the use of recombinant bone morphogenetic protein in  spinal fusion
      surgery: are stem cells an alternative?

PMID- 24877231
TI  - Medicine in small doses: Avoiding prolonged opioid prescribing after  major
      surgery.

PMID- 24877232
TI  - Adaptive ageing surgeons.
AB  - The surgical workforce is ageing. This will impact on future workforce supply and
      planning, as well as the professional performance and welfare of surgeons
      themselves. This paper is a 'call to arms' to surgeons to consider the complex
      problem of advancing years and surgical performance. We aim to promote discussion
      about the issue of ageing as it relates to surgeons, while exploring ways in
      which successful ageing in surgeons may be promoted. The task-specific aspects of
      surgical practice suggest that it is a physically and cognitively demanding task,
      reliant on a range of fine motor, sensory, visuospatial, reasoning, memory and
      processing skills. Many of these skills potentially decline with age, although
      there is great inter-individual variation, particularly in cognitive performance.
      Nevertheless, there is some consensus in the literature that age-related
      cognitive changes exist in a proportion of surgeons, and there is an increase in
      operative mortality rates for certain surgical procedures performed by older and
      more experienced surgeons. In the absence of mandatory retirement, guidance is
      needed in regard to individualizing the timing of retirement and encouraging
      reflective and adaptive practice based on insight into how one's skills and
      performance may change with age. This may be best facilitated by some form of
      informed and guided self-monitoring or 'self-screening'. It should be emphasized
      that self-screening is not a form of self-treatment but aims to enhance insight,
      using a tool kit of resources to promote adaptive ageing. Moreover, self
      screening should not be restricted to cognition, which is only part of the
      picture of ageing, but extended to emphasize the maintenance of mental and
      physical wellness, and the acceptance of independent professional treatment and
      support when required.

PMID- 24877233
TI  - Appendiceal neuroendocrine neoplasms in the era of laparoscopic  appendicectomy.
AB  - BACKGROUND: Incidental appendiceal neuroendocrine neoplasms are identified in 1%
      of surgical resections for suspected appendicitis. A proportion of these patients
      will require further surgery because of high risk features, which include
      mesoappendiceal involvement or an involved margin. While an open appendicectomy
      technique usually involves en bloc mesoappendiceal resection, the increasingly
      common laparoscopic method often skeletonizes the appendix, leaving the
      mesoappendix in situ. This retrospective observational study investigates whether
      routine resection of the mesoappendix rather than skeletonization would reduce
      the need for further surgery in patients with an incidental finding of
      appendiceal neuroendocrine neoplasm. METHODS: We included appendicectomies
      performed over an 11-year period at Auckland City Hospital and identified all
      cases of incidental appendiceal neuroendocrine neoplasms. Histological data were
      collected to assess the risk of lymphatic spread and need for further surgery.
      Mesoappendix resection versus preservation and its effect on the recommendation
      for further surgery was recorded. RESULTS: An appendiceal neuroendocrine neoplasm
      was present in 73 (1%) of 7109 appendicectomy specimens. Of these, 10 patients
      (14%) required right hemicolectomy. Five of these could potentially have been
      spared the need for further surgery had the mesoappendix been removed en bloc
      with the appendix. DISCUSSION: We recommend en bloc mesoappendix resection during
      appendicectomy in order to better stage the neoplasm and reduce the need for
      unnecessary further surgery.

PMID- 24877234
TI  - Evaluation of two chlorhexidine-alcohol-based skin disinfectants in blood
      donation setting.
AB  - BACKGROUND: Source reduction is important in minimizing bacterial-contaminated
      risk of blood products, but previous evaluation of chlorhexidine (CHX) was
      confounded by inability of Tween and lecithin to neutralize CHX. The study aims
      to address this limitation and also evaluates the effectiveness of two CHX
      alcohol-based skin disinfectants in blood donation setting. METHODS: A two-stage
      observational study was conducted. A single step 2% chlorhexidine gluconate/70%
      isopropyl alcohol brush (CHX/IPA-1) was first compared with current skin
      disinfection procedure consisting of sequential application of 10% povidone
      iodine and 70% isopropyl alcohol (PI/IPA). Standard plates with conventional
      neutralizers (0.3% Tween-80, 0.1% lecithin) were used to enumerate residual
      bacterial counts. Then, CHX/IPA-1 was compared with another applicator CHX/IPA-2
      with identical disinfectant contents using in-house plates with neutralizers (3%
      Tween-80, 0.3% lecithin, 0.1% histidine, 0.5% sodium thiosulphate, 3% saponin, 1%
      ether sulphate) having enhanced ability to neutralize CHX. RESULTS: All three
      products were found to reduce plate counts by > 2 log10 after disinfection. The
      CHX/IPA-1 group gave fewer residual bacterial growth on standard plates than
      PI/IPA group (5.9% vs. 61.7%, P < 0.001). With the use of in-house plates,
      residual bacterial growth was of no difference in both CHX/IPA-1 and CHX/IPA-2
      groups (42.5% vs. 49.4%, P = 0.26). CONCLUSION: Good efficacy was observed with
      one-stage application of CHX/IPA in predonation skin disinfection and it could
      replace PI/IPA. However, the efficacy of CHX/IPA could be grossly overestimated
      in testing with standard plates because of insufficient neutralization

PMID- 24877235
TI  - Can change in FRAX score be used to "treat to target"? A population-based cohort
      study.
AB  - It is unknown how responsive the Fracture Risk Assessment (FRAX) tool is to
      osteoporosis treatment (OTX) or whether it can serve as a target for "goal
      directed" treatment. We studied 11,049 untreated women aged >=50 years undergoing
      baseline and follow-up DXA examinations in Manitoba, Canada. We identified
      clinical risk factors, intervening OTX based on medication possession ratios
      (MPR),and incident fractures. FRAX scores for major osteoporotic and hip
      fractures were computed for each scan using the most current(updated) FRAX
      inputs. Over 4 years, median FRAX scores showed an increase of 1.1% for major
      fractures and 0.3% for hip fractures,including women highly adherent to OTX (0.6%
      and 0.1% increases). Few (2.2%) highly adherent women had a decrease in major
      fracture probability exceeding 4%, whereas 9.0% had a decrease in hip fracture
      probability exceeding 1%. Compared with untreated women, OTX was associated with
      a higher dose-dependent likelihood of attenuating the expected increase in major
      fracture risk:adjusted odds ratios (aOR) 2.3 (95% confidence interval [CI] 1.8
      2.9) for MPR <0.50; 7.3 (95% CI 5.6-9.6) for MPR 0.50-0.79; and 12.0(95% CI 9.5
      15.2) for MPR >=0.80. In the 4 years after the second DXA scan, 620 (6%) women
      had major fractures (152 hip fractures). FRAX scores were strongly predictive of
      incident major fractures (adjusted hazard ratios [aHR] per SD increase in FRAX
      1.8, 95%CI 1.7-1.9) and hip fractures (aHR per SD 4.5, 95% CI 3.7-5.7); however,
      change in FRAX score was not independently associated with major fracture (p=0.8)
      or hip fracture (p=0.3). In conclusion, FRAX scores slowly increased over time,
      and this increase was attenuated but not prevented by treatment. Few women had
      meaningful reductions in FRAX scores, and change in FRAX score did not
      independently predict incident fracture, suggesting that FRAX with BMD is not
      responsive enough to be used as a target for goal-directed treatment.

PMID- 24877236
TI  - Prevalence of Treponema pallidum DNA among blood donors with two different
      serologic tests profiles for syphilis in Sao Paulo, Brazil.
AB  - The presence of Treponema pallidum DNA was assessed by real-time PCR in samples
      of blood donors with reactive serologic tests for syphilis. Treponema pallidum
      DNA was detected in two (1.02%) of 197 samples of VDRL>8, EIA+ and FTA-ABS+
      donors, and in no sample from 80 VDRL-, EIA+ and FTA-ABS+ donors. Donors VDRL-,
      EIA+ and FTA-ABS+ lack demonstrable T. pallidum DNA in their blood and are unlike
      to transmit syphilis. Donors VDRL>8, EIA+ and FTA-ABS+ carry the risk of syphilis
      infectivity even in concomitance to antibodies detection. Serologic screening for
      syphilis may still play a role to prevent its transfusion transmission.

PMID- 24877237
TI  - Pilot study of 'Scissorhands' technique for gastric  endoscopic submucosal
      dissection using novel gel and  endoscopic scissors in a porcine model (with
      video).
AB  - BACKGROUND AND AIM: Endoscopic submucosal dissection (ESD) is a complex procedure
      and is associated with significant risks. The aims of this pilot study were to
      study feasibility and procedural times of gastric ESD using a novel gel and
      endoscopic scissors in a porcine model. METHODS: Simulated 3-cm gastric
      submucosal lesions were created in a porcine model. Subsequently, viscous gel was
      injected into the created bleb. A needle knife was used to create an initial
      incision when needed. Endoscopic scissors were then used for circumferential
      incision around the simulated submucosal lesions. The inserted coil (i.e.
      submucosal lesion) was then removed. The submucosal surface was carefully
      examined for signs of injury. Procedural times were recorded. RESULTS: ESD was
      carried out in four consecutive pigs using the 'Scissorhands' technique. A small
      submucosal incision was created a using needle knife in the first pig and
      electrocautery was not used in the remaining three pigs. Circumferential incision
      using the scissors was done successfully in all pigs. Submucosal dissection was
      not required in any case. 'Auto-dissection' of created lesions by the gel was
      noted to be complete in all cases. Inserted coils were noted in the submucosal
      space during all experiments and were removed. All lesions were successfully
      resected en bloc. The mean procedure time was 19 min (range 13-22 min).
      CONCLUSION: The combined technique of endoscopic scissors for circumferential
      incision and viscous gel for submucosal dissection permitted easy, safe and
      efficient gastric ESD. Electrocautery may be avoided and its consequent adverse
      events (e.g. perforation).

PMID- 24877238
TI  - JK null alleles identified from Japanese individuals with Jk(a-b-) phenotype.
AB  - The Kidd blood group system consists of three common phenotypes: Jk(a+b-), Jk(a
      b+) and Jk(a+b+), and one rare phenotype, Jk(a-b-). Jka/Jkb polymorphism is
      associated with c.838G>A (p.Asp280Asn) in exon 9 of the JK (SLC14A1) gene, and
      the corresponding alleles are named JK*01 and JK*02. The rare phenotype Jk(a-b-)
      was first found in a Filipina of Spanish and Chinese ancestry, and to date,
      several JK null alleles responsible for the Jk(a-b-) phenotype have been
      reported. We report seven novel JK null alleles, 4 with a JK*01 background and 3
      with a JK*02 background, identified from Jk(a-b-) Japanese.

PMID- 24877239
TI  - Double-balloon colonoscopy carried out by a trainee after  incomplete
      conventional colonoscopy.
AB  - BACKGROUND AND AIM: It has been reported that double-balloon colonoscopy (DBC) is
      useful for patients after failed colonoscopy. In most cases previously reported,
      expert colonoscopists have carried out DBC. However, DBC may not require
      significant expertise. The objective of the present study is to assess DBC
      carried out by an inexperienced colonoscopist in patients referred after
      previously incomplete colonoscopy. METHODS: In a single center between June 2011
      and September 2012, we enrolled 28 consecutive patients referred following
      incomplete conventional colonoscopy. The reported reasons for previous failed
      colonoscopy were severe pain during the procedure in 15, long redundant colon in
      13 and sigmoid fixation in eight. Under instruction by an experienced
      colonoscopist, all procedures were carried out by a gastroenterology trainee with
      little colonoscopy experience. A double-balloon instrument with carbon dioxide
      insufflation was used under fluoroscopic guidance, with i.v. sedation. Cecal
      intubation rate, time to cecum and patient-reported pain using a visual analog
      scale (0 to 10) were evaluated. RESULTS: The trainee achieved a cecal intubation
      in all patients (100%) without primary involvement by the experienced
      colonoscopist. Time to cecum ranged from 6 min to 66 min (median time to cecum 15
      min 55 s). No patients required additional sedation. Visual analogue pain scores
      ranged from 0/10 to 10/10 (median score 2.5/10). There were no complications.
      CONCLUSION: DBC may enable inexperienced colonoscopists to achieve total
      colonoscopy after previously incomplete conventional colonoscopy.

PMID- 24877240
TI  - Relationship between frequency of surveillance  colonoscopy and colorectal cancer
      prevention.
AB  - BACKGROUND AND AIM: The impact of frequent colonoscopy on colorectal cancer (CRC)
      remains unclear. The present study aimed to determine the relationship between
      frequency of surveillance colonoscopy and CRC prevention. METHODS: From April
      2010 to April 2011, patients who underwent surveillance colonoscopy after
      screening and polypectomy in four Japanese endoscopy centers were enrolled in
      this multicenter historical cohort study. Patients were classified into the
      following two groups according to the findings of past colonoscopy: a low-risk
      group (no neoplasia or 1-2 cumulative adenomas <10 mm) and an increased-risk
      group (advanced adenoma or >= 3 cumulative adenomas). The relationship between
      colonoscopy frequency within the previous 5 years and the prevalence of advanced
      neoplasia in each group was analyzed using multiple logistic regression. RESULTS:
      The final analysis included 2391 patients. In the low-risk group, the odds ratios
      for advanced adenoma in patients undergoing moderately frequent colonoscopy (2-3
      times within the previous 5 years), and frequent colonoscopy (>= 4 times within 5
      years) were 0.33 (95% confidence interval [CI], 0.14-0.81) and 0.21 (95% CI, 0.02
      1.60), respectively, compared with infrequent colonoscopy (once or not at all
      within 5 years). In the increased-risk group, the respective odds ratios were
      0.48 (95% CI, 0.28-0.83) and 0.28 (95% CI, 0.12-0.64). CONCLUSIONS: Although
      frequent colonoscopy provides benefits against advanced adenoma, the optimal
      benefit was achieved at 2-3 times. With very frequent colonoscopy (i.e. >= 4
      times within 5 years), the additional risk reduction for advanced adenoma was
      relatively small.

PMID- 24877241
TI  - Lactoferrin stimulates osteoblast differentiation through PKA and p38 pathways
      independent of lactoferrin's receptor LRP1.
AB  - Lactoferrin (LF) has been established as a potent anabolic factor for bone health
      both in vivo and in vitro. However, the molecular mechanisms underlying LF's
      action are still largely unknown. Here, we explore the signaling pathways that
      mediate LF's beneficial effect on osteoblast differentiation. In primary
      osteoblast and preosteoblast MC3T3-E1, LF promoted alkaline phosphatase
      (ALP)activity, osteocalcin (OCN) secretion, and mineralization. Along with this
      enhanced osteogenic differentiation, activation of p38 mitogen-activated protein
      kinase (MAPK) was detected in LF-treated MC3T3-E1 cells. Downregulating p38 with
      selective inhibitor SB203580 or p38a small interfering RNA (siRNA) attenuated the
      effect of LF on osteogenesis. Furthermore, knockdown of p38alpha significantly
      decreased LF-induced Runt-related transcription factor 2 (Runx2) phosphorylation.
      According to previous studies and our results, we speculated that LF-induced
      osteoblast proliferation and differentiation were two relatively separate
      processes controlled by extracellular signal-regulated kinase 1/2 (ERK1/2) and
      p38 pathways, respectively. Besides p38 MAPK activation, protein kinase A(PKA)
      was also activated in MC3T3-E1 cells. PKA inhibitor H89 significantly inhibited
      LF-induced p38 activation, ALP activity, and OCN secretion, indicating that PKA
      possibly acted as an upstream kinase of p38. In order to further identify the
      role of LF's receptor low-density lipoprotein receptor-related protein 1 (LRP1),
      we constructed LRP1 stable-knockdown MC3T3-E1 cells. Neither LRP1 antagonist
      receptor associated protein (RAP), nor LRP1 knockdown approach could attenuate
      the LF-induced osteogenesis, implying that LF stimulated osteoblast
      differentiation via an LRP1-independent pathway. Taken together, the present work
      indicated that LF stimulated MC3T3-E1 preosteoblast differentiation mainly
      through LRP1-independent PKA and p38 signaling pathways. These results provided
      the first evidence of the signaling mechanisms of LF's effect on osteoblast
      differentiation.

PMID- 24877242
TI  - Randomized controlled trial comparing stylet-free  endoscopic ultrasound-guided
      fine-needle aspiration  with 22-G and 25-G needles.
AB  - BACKGROUND AND AIM: Previous studies comparing endoscopic ultrasound-guided fine
      needle aspiration (EUS-FNA) results with different gauge needles have all been
      carried out with the stylet in place and show no clear advantage to the larger 22
      G needle. Similar data for stylet-free EUS-FNA (SF-EUS-FNA) are unavailable. The
      aim of the present study was to determine whether diagnostic yield and specimen
      adequacy is superior with the 22-G needle as compared to the 25-G needle.
      METHODS: All patients >= 18 years referred for solid-lesion EUS-FNA were
      eligible. Patients with suspected diagnosis of lymphoma, gastrointestinal stromal
      tumor, sarcoidosis, significant coagulopathy (international normalized ratio >
      1.5 or platelets < 50000/mm(3)), use of clopidogrel within 7 days of EUS, and
      pregnancy were excluded. The two needles were compared regarding diagnostic
      yield, sample adequacy, bloodiness, ease of puncture, visibility, number of
      passes, failures, and complications. RESULTS: One hundred and twenty consecutive
      patients were included and 126 lesions were sampled. Sensitivity, specificity,
      positive predictive value and negative predictive value for the 22-G SF-EUS-FNA
      were 83%, 100%, 100% and 56%, respectively, and for the 25-G SF-EUS-FNA were
      88.8%, 100%, 100% and 76.5%, respectively (P=NS). There were no significant
      differences between the 22-G and the 25-G FNA needles in sample adequacy,
      bloodiness, ease of puncture, FNA failure, visibility, number of passes and
      complications; and no significant differences between either needle were found in
      relation to lesion site. CONCLUSION: For SF-EUS-FNA, the larger 22-G needle
      offers no advantage over the smaller 25-G needle.

PMID- 24877243
TI  - Circulating levels of carboxy-methyl-lysine (CML) are associated with hip
      fracture risk: the Cardiovascular Health Study.
AB  - Advanced glycation end products (AGE) in bone tissue are associated with impaired
      biomechanical properties and increased fracture risk. Here we examine whether
      serum levels of the AGE carboxy-methyl-lysine (CML) are associated with risk of
      hip fracture.We followed 3373 participants from the Cardiovascular Health Study
      (age 78 years; range, 68-102 years; 39.8% male) for a median of 9.22 years
      (range, 0.01-12.07 years). Rates of incident hip fracture were calculated by
      quartiles of baseline CML levels, and hazard ratios were adjusted for covariates
      associated with hip fracture risk. A subcohort of 1315 participants had bone
      mineral density (BMD)measurement. There were 348 hip fractures during follow-up,
      with incidence rates of hip fracture by CML quartiles of 0.94, 1.34, 1.18, and
      1.69 per 100 participant-years. The unadjusted hazard ratio of hip fracture
      increased with each 1 SD increase (189 ng/mL) of CML level (hazard ratio, 1.27;
      95% confidence interval [CI], 1.16-1.40]; p<0.001). Sequential adjustment for
      age, gender, race/ethnicity,body mass index (BMI), smoking, alcohol consumption,
      prevalent coronary heart disease (CHD), energy expenditure, and estimated
      glomerular filtration rate (based on cystatin C), moderately attenuated the
      hazard ratio for fracture (1.17; 95% CI, 1.05-1.31; p=0.006).In the cohort with
      BMD testing, total hip BMD was not significantly associated with CML levels. We
      conclude that increasing levels of CML are associated with hip fracture risk in
      older adults, independent of hip BMD. These results implicate AGE in the
      pathogenesis of hip fractures.

PMID- 24877246
TI  - Comment on "the ductus venosus: proposal for a uniform anatomical definition".

PMID- 24877247
TI  - Robotics in general surgery: an evidence-based review.
AB  - Since its introduction, robotic surgery has been rapidly adopted to the extent
      that it has already assumed an important position in the field of general
      surgery. This rapid progress is quantitative as well as qualitative. In this
      review, we focus on the relatively common procedures to which robotic surgery has
      been applied in several fields of general surgery, including gastric, colorectal,
      hepato-biliary-pancreatic, and endocrine surgery, and we discuss the results to
      date and future possibilities. In addition, the advantages and limitations of the
      current robotic system are reviewed, and the advanced technologies and
      instruments to be applied in the near future are introduced. Such progress is
      expected to facilitate the widespread introduction of robotic surgery in
      additional fields and to solve existing problems.

PMID- 24877245
TI  - Skeletal structure in postmenopausal women with osteopenia and fractures is
      characterized by abnormal trabecular plates and cortical thinning.
AB  - The majority of fragility fractures occur in women with osteopenia rather than
      osteoporosis as determined by dual-energy X-ray absorptiometry (DXA). However, it
      is difficult to identify which women with osteopenia are at greatest risk. We
      performed this study to determine whether osteopenic women with and without
      fractures had differences in trabecular morphology and biomechanical properties
      of bone. We hypothesized that women with fractures would have fewer trabecular
      plates, less trabecular connectivity, and lower stiffness. We enrolled 117
      postmenopausal women with osteopenia by DXA (mean age 66 years; 58 with fragility
      fractures and 59 nonfractured controls). All had areal bone mineral density
      (aBMD) measured by DXA. Trabecular and cortical volumetric bone mineral density
      (vBMD), trabecular microarchitecture, and cortical porosity were measured by high
      resolution peripheral computed tomography (HR-pQCT) of the distal radius and
      tibia. HR-pQCT scans were subjected to finite element analysis to estimate whole
      bone stiffness and individual trabecula segmentation (ITS) to evaluate trabecular
      type (as plate or rod), orientation, and connectivity.Groups had similar age,
      race, body mass index (BMI), and mean T-scores. Fracture subjects had lower
      cortical and trabecular vBMD, thinner cortices, and thinner, more widely
      separated trabeculae. By ITS, fracture subjects had fewer trabecular plates, less
      axially aligned trabeculae, and less trabecular connectivity. Whole bone
      stiffness was lower in women with fractures. Cortical porosity did not differ.
      Differences in cortical bone were found at both sites, whereas trabecular
      differences were more pronounced at the radius.In summary, postmenopausal women
      with osteopenia and fractures had lower cortical and trabecular vBMD; thinner,
      more widely separated and rodlike trabecular structure; less trabecular
      connectivity; and lower whole bone stiffness compared with controls,despite
      similar aBMD by DXA. Our results suggest that in addition to trabecular and
      cortical bone loss, changes in plate and rod structure may be important
      mechanisms of fracture in postmenopausal women with osteopenia.

PMID- 24877244
TI  - Innocent until proven guilty: mechanisms and roles of Streptococcus-Candida
      interactions in oral health and disease.
AB  - Candida albicans and streptococci of the mitis group colonize the oral cavities
      of the majority of healthy humans. While C. albicans is considered an
      opportunistic pathogen, streptococci of this group are broadly considered
      avirulent or even beneficial organisms. However, recent evidence suggests that
      multi-species biofilms with these organisms may play detrimental roles in host
      homeostasis and may promote infection. In this review we summarize the literature
      on molecular interactions between members of this streptococcal group and C.
      albicans, with emphasis on their potential role in the pathogenesis of
      opportunistic oral mucosal infections.

PMID- 24877248
TI  - Development and validation of a prediction algorithm for use by health
      professionals in prediction of recurrence of major depression.
AB  - BACKGROUND: There exists very little evidence to guide clinical management for
      preventing recurrence of major depression. The objective of this study was to
      develop and validate a prediction algorithm for recurrence of major depression.
      METHODS: Wave 1 and wave 2 longitudinal data from the U.S. National
      Epidemiological Survey on Alcohol and Related Condition (2001/2002-2003/2004)
      were used. Participants with a major depressive episode at baseline and who had
      visited health professionals for depression were included in this analysis (n =
      2,711). Mental disorders were assessed based on the DSM-IV criteria. RESULTS:
      With the development data (n = 1,518), a prediction model with 19 unique factors
      had a C statistics of 0.7504 and excellent calibration (P = .23). The model had a
      C statistics of 0.7195 in external validation data (n = 1,195) and 0.7365 in
      combined data. The algorithm calibrated very well in validation data. In the
      combined data, the 3-year observed and predicted risk of recurrence was 25.40%
      (95% CI: 23.76%, 27.04%) and 25.34% (95% CI: 24.73%, 25.95%), respectively. The
      predicted risk in the 1st and 10th decile risk group was 5.68% and 60.21%,
      respectively. CONCLUSIONS: The developed prediction model for recurrence of major
      depression has acceptable discrimination and excellent calibration, and is
      feasible to be used by physicians. The prognostic model may assist physicians and
      patients in quantifying the probability of recurrence so that physicians can
      develop specific treatment plans for those who are at high risk of recurrence,
      leading to personalized treatment and better use of resources.

PMID- 24877249
TI  - What effect is really being measured? An alternative explanation of paradoxical
      phenomena in studies of osteoarthritis progression.

PMID- 24877250
TI  - Suboptimal management of unfractionated heparin compared  with low-molecular
      weight heparin in the management of  pulmonary embolism.
AB  - BACKGROUND: Both low-molecular-weight heparin (LMWH) and unfractionated heparin
      (UFH) have been shown to be equivalent in efficacy and safety profiles for the
      management of pulmonary embolism (PE). AIMS: To assess the real world management
      of anticoagulation in PE in a tertiary hospital setting. METHODS: An audit of
      patients with a new diagnosis of PE from March 2011 to March 2012. Data collected
      included patient demographics, anticoagulant, complication, mortality, time to
      first administration, frequency of monitoring and dose adjustment for UFH, time
      to therapeutic range for UFH (based on activated partial thromboplastin time) and
      length of hospital stay. RESULTS: Of the 211 patients who were included, 139 were
      admitted through the Emergency Department, and 45 were managed with UFH. There
      was no significant difference in time to initial dose between those treated with
      LMWH and UFH (192 vs 98 min, P = 0.16). For UFH, average time to therapeutic
      range was 594 min (range 87-2257 min). During the course of UFH therapy, only 22%
      of activated partial thromboplastin time was within therapeutic range, while 44%
      was above and 33% was below therapeutic range. Average number of UFH dose
      adjustment was 5. Increasing weight and higher baseline fibrinogen levels
      significantly delayed time to therapeutic range for patients on UFH (P = 0.02 and
      0.04 respectively). Up to 18 months following PE, overall mortality rate was 28%,
      with no significant difference between LMWH and UFH (28% vs 29%). CONCLUSION: PE
      was predominantly managed with LMWH. UFH was suboptimally managed when used,
      although there was no impact on mortality rate.

PMID- 24877251
TI  - Cost effectiveness of duloxetine for osteoarthritis: a Quebec societal
      perspective.
AB  - OBJECTIVE: To assess the cost effectiveness of duloxetine compared to other oral
      postacetaminophen treatments for osteoarthritis (OA) from a Quebec societal
      perspective. METHODS: A cost-utility analysis was performed enhancing the Markov
      model from the 2008 OA guidelines of the National Institute for Health and
      Clinical Excellence (NICE). The NICE model was extended to include opioid and
      antidepressant comparators, adding titration, discontinuation, and relevant
      adverse events (AEs). Comparators included duloxetine, celecoxib, diclofenac,
      naproxen, hydromorphone, and oxycodone extended release (oxycodone). AEs included
      gastrointestinal and cardiovascular events associated with nonsteroidal
      antiinflammatory drugs (NSAIDs), as well as fracture, opioid abuse, and
      constipation, among others. Costs and incremental cost-effectiveness ratios
      (ICERs) were estimated in 2011 Canadian dollars. The base case modeled a cohort
      of 55-year-old patients with OA for a 12-month period of treatment, followed by
      treatment from a basket of post-discontinuation oral therapies until death.
      Sensitivity analyses (one-way and probabilistic) were conducted. RESULTS:
      Overall, naproxen was the least expensive treatment, whereas oxycodone was the
      most expensive. Duloxetine accumulated the highest number of quality-adjusted
      life years (QALYs), with an ICER of $36,291 per QALY versus celecoxib. Duloxetine
      was dominant over opioids. In subgroup analyses, ICERs for duloxetine versus
      celecoxib were $15,619 and $20,463 for patients at high risk of NSAID-related AEs
      and patients ages >65 years, respectively. CONCLUSION: Duloxetine was cost
      effective for a cohort of 55-year-old patients with OA, and more so in older
      patients and those with greater AE risks.

PMID- 24877252
TI  - Histopathological differences between prostate cancer foci that are  detected and
      missed using multiparametric magnetic resonance  imaging in Korean patients.
AB  - OBJECTIVES: We investigated whether multiparametric magnetic resonance imaging is
      appropriate to localize prostate cancer foci in Koreans. METHODS: A total of 141
      prostate cancer foci in 115 prostate specimens from patients who had undergone
      radical prostatectomy with preoperative 3 Tesla multiparametric magnetic
      resonance imaging including T2-weighted imaging, diffusion weighted imaging and
      magnetic resonance spectroscopy. Differences in the histopathological findings
      between detected and undetected prostate cancer foci on multiparametric magnetic
      resonance imaging were investigated. RESULTS: The mean tumor size was 1.9 cm, and
      31.9%, 48.9%, and 19.9% of the patients had Gleason scores of 6, 7, or >=8,
      respectively. The detection rates of prostate cancer foci were 54.6%, 57.4%,
      55.3%, and 45.4% on multiparametric magnetic resonance imaging, T2-weighted
      imaging, diffusion weighted imaging, and magnetic resonance spectroscopy,
      respectively. On multivariate analysis, tumor size >=1.5 cm (odds ratio 3.1; 95%
      confidence interval 1.31-7.49), Gleason score >7 (4 + 3; odds ratio 2.9; 95%
      confidence interval 1.05-8.05), and a malignant epithelium/stroma ratio of >=60%
      (odds ratio 2.9; 95% confidence interval 1.14-7.20) were significant independent
      predictors of prostate cancer foci detection on multiparametric magnetic
      resonance imaging and diffusion weighted imaging. In a multivariate linear model
      analysis, the apparent diffusion coefficient value was inversely associated with
      maximum tumor diameter (beta = -0.242, P < 0.05), Gleason score (beta = -0.234, P
      < 0.05)and high malignant epithelium/stroma ratio (beta = -0.229, P < 0.05).
      CONCLUSIONS: Distinct histological differences between prostate cancer foci that
      were detected and missed by multiparametric magnetic resonance imaging can be
      identified. Despite limitations, multiparametric magnetic resonance imaging seems
      useful for determining prostate cancer in Korean patients, particularly with
      Gleason score >7 and tumor diameter>1.5 cm.

PMID- 24877253
TI  - Long-term tolerance and efficacy of adjunctive exenatide  therapy on glycaemic
      control and bodyweight in type 2  diabetes: a retrospective study from a
      specialist diabetes  outpatient clinic.
AB  - BACKGROUND: Weight gain and hypoglycaemia are common adverse effects associated
      with anti-diabetic treatments. AIM: Our aim was to evaluate the long-term effects
      of adjunctive exenatide therapy on weight loss and glycaemic control in patients
      with type 2 diabetes. METHODS: A review of medical records in a specialist
      diabetes clinic over 5 years identified 446 patients who were prescribed
      exenatide therapy. We examined change in glycosylated haemoglobin (HbA1c),
      weight, albumin-creatinine ratio and hypoglycaemic medication during 24 months
      follow up. RESULTS: Subjects were aged 59 +/- 10 years (49% women) and received
      exenatide in combination with oral agents and insulin (47%). During an average of
      17 +/- 14 months follow up, 51% (more women than men; odds ratio 1.69, 95%
      confidence interval 1.14-2.49) remained on treatment. Lack of efficacy (33%)
      and/or gastrointestinal (27%) side-effects were the main reasons for treatment
      cessation. At 24 months, there was a reduction in HbA1c of 0.7 +/- 1.2% and
      weight loss of 4.3 +/- 5.2 kg. Change in HbA1c was similar regardless of
      concurrent insulin therapy, yet insulin was associated with greater weight
      reduction (4.8 +/- 5.3 vs 3.8 +/- 5.1 kg, P = 0.016). Independent predictors of
      HbA1c response were higher baseline HbA1c, longer duration of diabetes and use of
      insulin or sulfonylureas at study end. Predictors of weight response were
      baseline use of insulin or thiazolidinediones, increased age, female sex and
      sulfonylurea or thiazolidinediones at study end. Longer exenatide treatment
      duration was favourable for reducing HbA1c and weight. CONCLUSIONS: Exenatide is
      effective in reducing HbA1c and weight, regardless of concurrent insulin, and in
      a specialist diabetes outpatient clinic, is recommended for use in clinical
      practice.

PMID- 24877254
TI  - Prediction of non-biochemical recurrence rate after radical prostatectomy in a
      Japanese cohort: development of a postoperative nomogram.
AB  - OBJECTIVE: To develop a nomogram based on postoperative factors and prostate
      specific antigen levels to predict the non-biochemical recurrence rate after
      radical prostatectomy ina Japanese cohort. METHODS: A total of 606 Japanese
      patients with T1-3N0M0 prostate cancer who underwent radical prostatectomy and
      pelvic lymph node dissection at Tokyo Medical University hospital from 2000 to
      2010 were studied. A nomogram was constructed based on Cox hazard regression
      analysis evaluating the prognostic significance of serum prostate-specific
      antigen and pathological factors in the radical prostatectomy specimens. The
      discriminating ability of the nomogram was assessed by the concordance index (C
      index), and the predicted and actual outcomes were compared with a bootstrapped
      calibration plot. RESULTS: With a mean follow up of 60.0 months, a total of 187
      patients (30.9%) experienced biochemical recurrence, with a 5-year non
      biochemical recurrence rate of 72.3%. Based on a Cox hazard regression model, a
      nomogram was constructed to predict non-biochemical recurrence using serum
      prostate-specific antigen level and pathological features in radical
      prostatectomy specimens. The concordance index was 0.77, and the calibration
      plots appeared to be accurate. CONCLUSIONS: The postoperative nomogram described
      here can provide valuable information regarding the need for adjuvant/salvage
      radiation or hormonal therapy in patients after radical prostatectomy.

PMID- 24877255
TI  - Internal medicine in the bush: a clinical audit of a rural and  remote outreach
      programme.
AB  - BACKGROUND: Provision of internal medicine services in rural Australia is always
      problematic. AIM: The aim was to undertake an audit of an outreach service
      operating in Northern New South Wales since 2006. METHODS: The service is
      conducted eight times a year, involving a consultant and an advanced trainee who
      travel by car to the towns of Moree and Mungindi and conduct clinics in a general
      practice setting, an Aboriginal medical service and a local health district
      clinic. Since 2008, a cardiology service and a diabetes service have been added
      on a fly-in fly-out basis. Case records of all patients enrolled in the service
      between February 2006 and July 2013 were reviewed in determining the
      demographics, clinical presentations and level of service coverage. The
      experience of the authors in establishing the service provided insights into the
      challenges and the success factors involved. RESULTS: Five hundred and eighty
      three patients were seen on a total of 1070 occasions relating to a wide variety
      of clinical presentations. Of these, 31.3% were indigenous compared with 20% in
      the local statistical area, and both indigenous and non-indigenous patients were
      seen in all settings. Patients fell into 15 different diagnostic categories with
      indigenous patients more likely to present for diabetes (P < 0.001) and hepatitis
      B (P < 0.01), but less likely to present for treatment of hepatitis C (P < 0.01).
      CONCLUSIONS: In providing an outreach service to a mixed community, flexibility
      in both setting and personnel are essential. Diabetes and liver disease are
      highly prevalent in indigenous patients, but the low numbers presenting for
      hepatitis C requires further study.

PMID- 24877256
TI  - Molecular dynamics simulations of certain RGD-based peptides from Kistrin provide
      insight into the higher activity of REI-RGD34 protein at higher temperature.
AB  - To determine the bioactive conformation required to bind with receptor aIIbb3,
      the peptide sequence RIPRGDMP from Kistrin was inserted into CDR 1 loop region of
      REI protein, resulting in REI-RGD34. The activity of REI-RGD34 was observed to
      increase at higher temperature towards the receptor aIIbb3. It could be justified
      in either way: the modified complex forces the restricted peptide to adapt
      bioactive conformation or it unfolds the peptide in a way that opens its binding
      surface with high affinity for receptor. Here, we model the conformational
      preference of RGD sequence in RIPRGDMP at 25 and 42  degrees C using multiple MD
      simulations. Further, we model the peptide sequence RGD, PRGD and PRGDMP from
      kistrin to observe the effect of flanking residues on conformational sampling of
      RGD. The presence of flanking residues around RGD peptide greatly influenced the
      conformational sampling. A transition from bend to turn conformation was observed
      for RGD sequence at 42  degrees C. The turn conformation shows pharmacophoric
      parameters required to recognize the receptor aIIbb3. Thus, the
      temperaturedependent activity of RIPRGDMP when inserted into the loop region of
      REI can be explained by the presence of the turn conformation. This study will
      help in designing potential antagonist for the receptor aIIbb3.

PMID- 24877257
TI  - Epichloe spp. associated with grasses: new insights on life cycles, dissemination
      and evolution.
AB  - Epichloe species with their asexual states are specialized fungi associated with
      cool-season grasses. they grow endophytically in tissues of aerial parts of host
      plants to form systemic and mostly asymptomatic associations. Their life cycles
      may involve vertical transmission through host seeds and/or horizontal
      transmission from one plant to other plants of the same species through fungal
      propagules. Vertical transmission has been well studied, but comparatively little
      research has been done on horizontal dissemination. The goal of this review is to
      provide new insights on modes of dissemination of systemic grass endophytes. The
      review addresses recent progress in research on (i) the process of growth of
      Epichloe endophytes in the host plant tissues, (ii) the types and development of
      reproductive structures of the endophyte, (iii) the role of the reproductive
      structures in endophyte dissemination and host plant infection processes and (iv)
      some ecological and evolutionary implications of their modes of dissemination.
      Research in the Epichloe grass endophytes has accelerated in the past 25 y and
      has demonstrated the enormous complexity in endophyte-grass symbioses. There
      still remain large gaps in our understanding of the role and functions of these
      fungi in agricultural systems and understanding the functions, ecology and
      evolution of these endophytes in natural grass populations.

PMID- 24877259
TI  - Are you involved?

PMID- 24877260
TI  - A helping hand.

PMID- 24877258
TI  - March against austerity.

PMID- 24877261
TI  - In an MSW's shoes: Part two.

PMID- 24877262
TI  - Mind over matter: minimising the pain of labour (midwives 2011 7:20-1).

PMID- 24877263
TI  - Where to from here?

PMID- 24877264
TI  - Weight management. Watching diet while pregnant 'is safe'.

PMID- 24877266
TI  - An oasis of calm.

PMID- 24877265
TI  - The controversy of mapping genetics.

PMID- 24877267
TI  - The right tools for safe birth.

PMID- 24877268
TI  - Are you involved?

PMID- 24877269
TI  - Highlighting co screening.

PMID- 24877271
TI  - MSWs and the RCM.

PMID- 24877272
TI  - Getting our voice heard.

PMID- 24877273
TI  - Watching the figures.

PMID- 24877274
TI  - Report reflects birth rate diversity.

PMID- 24877275
TI  - The tragedy of stillbirths.

PMID- 24877277
TI  - At the coalface.

PMID- 24877278
TI  - The rise of the middle-aged mother.

PMID- 24877279
TI  - Euro vision.

PMID- 24877280
TI  - Home and away.

PMID- 24877281
TI  - Channelling maternity resources.

PMID- 24877301
TI  - Bilateral recession of the superior oblique in "A" pattern tropia.
AB  - A bilateral recession of an overacting superior oblique was performed in nine
      patients with "A" pattern ranging from 12 to 48 diopters, with an average of 24
      prism diopters.There were six esotropic and three exotropic subjects. In all
      cases but one, some surgery of one or two horizontal recti was done at same
      time.An under correction was observed in two patients, of respectively 13 and 9
      prism diopters. An overcorrection not exceeding 15 prism diopters was seen in six
      patients; in four it measured 3 prism diopters or less. A full correction was
      obtained in one case. The mean correction of "A" pattern was 25 prism
      diopters.Complications were not observed during the follow-up period.

PMID- 24877346
TI  - Optociliary veins, visual loss, and disc pallor in a child with a 22 year follow
      up.
AB  - A case of optociliary veins, disc pallor, and long-standing visual loss in an eye
      of a patient followed from age two to age 25 is presented. A review of the
      literature indicates the above triad to be usually suggestive of sphenoidal ridge
      meningioma. Our case, the youngest thus far reported in the literature, also
      developed ocular hypertension in this eye and exophthalmos. The patient has
      refused further diagnostic workup.

PMID- 24877354
TI  - The management of advanced rhabdomyosarcoma of the upper eyelid.
AB  - An advanced case of rhabdomyosarcoma of the upper eyelid is used to demonstrate
      and discuss the principles of diagnosis and proper management of this most
      malignant extra-ocular neoplasm in the orbital region.

PMID- 24877361
TI  - Retinal hamartoma in childhood.
AB  - Characteristic clinic details of two children affected with pigment-containing
      tumefactions of the posterior pole are described. The lesion although
      provisionally regarded as hamartomatous can, as in these two patients, exhibit
      inflammatory signs which may suggest a reactive inflammatory pathogenesis. Most
      tests are non-contributory, but fluorescence angiography and electro-oculography
      are of value in differential diagnosis. The former investigation has indicated
      that the pattern and intensity of vascular leakage in the mass may change over a
      period of a year.

PMID- 24877370
TI  - Subconjunctival cysticercosis.
AB  - Two cases of subconjunctival Cysticercus cellulosae have been reported. In one
      case the cyst presented in the lower fornix, while in the other it was found in
      the medial canthus. The literature has been reviewed.

PMID- 24877378
TI  - Abduction nystagmus.
AB  - An eight-year-old patient was seen with esotropia, a head turn to the right and
      nystagmus, more pronounced in abduction with either eye fixing. The fast phase of
      nystagmus was towards abduction of the fixing eye. In marked adduction (45
      degrees ), the direction of the fast phase of nystagmus was seen to reverse. The
      frequency of nystagmus was not affected by eye position or by which eye was
      fixing.Following recession of each medial rectus muscle the esotropia was
      eliminated. An interesting but unexplained postoperative finding was that the
      amplitude of nystagmus was greatest in the primary position only with fixation by
      the opposite eye.

PMID- 24877388
TI  - Optic disc anomalies and maternal ingestion of LSD.
AB  - two patients born to others habitually using LSD during pregnancy are described.
      Each infant had an isolated bilateral optic disc anomaly suggesting an early
      intrauterine insult. The possibility that LSD may express its teratogenicity in
      such relative benign fashion is suggested and the importance of further
      investigations concerning the etiology of disc anomalies is stressed.

PMID- 24877413
TI  - Late ocular recurrence of retinoblastoma after external radiation.

PMID- 24877419
TI  - Chloramphenicol-induced acute bilateral optic neuritis in cystic fibrosis.
AB  - An acute case of bilateral optic neuritis secondary to chloromycetin
      administration in a child with cystic fibrosis is described. We believe this to
      be the first description of the fluorescein angiographic finding in such case.

PMID- 24877437
TI  - Treatment of vernal keratoconjunctivitis with topical cromolyn sodium.
AB  - This paper presents five cases of steroid resistant vernal keratoconjunctivitis
      which were treated with cromolyn sodium. Four of the five patients had an
      associated punctate keratitis which cleared in this treatment. Topical
      application of cromolyn in the form of 4%aqueous solution appears to be an
      effective means for treating vernal keratoconjunctivitis .The drug is well
      tolerated and is without significant ocular side effects. The drug may be used in
      conjunction with topical corticosteroids without ill effect. More importantly,
      cromolyn may significantly reduce the need for topical corticosteroids.

PMID- 24877442
TI  - Modification of the Jensen procedure.
AB  - A modification of the Jensen procedure is presented in which the lateral two
      thirds of the superior and inferior rectus muscles and the center one-third of
      the lateral rectus are left uninvolved in order to reduce the possibility of
      anterior segment ischemia.

PMID- 24877449
TI  - Inferior rectus muscle fibrosis following orbital trauma.
AB  - Three cases of diployia and restriction of elevation developed several weeks
      after blunt trauma to the orbit. In no instance was an orbital floor fracture
      present, and all three cases demonstrated fibrosis and adhesions to the inferior
      rectus and oblique muscles.

PMID- 24877465
TI  - Prognosis in retinoblastoma: influence of histopathologic characteristics.
AB  - One hundred twenty-eight cases of retinoblastoma were reviewed. The mean age at
      diagnosis, presenting signs, clinical, and pathological features were
      investigated. Patients with bilateral tumors presented earlier and had a higher
      mortality rate than those with unilateral tumors. Histopathological features such
      as calcification, seeding into the vitreous, and the degree of differentiation
      had no significant effect on prognosis. There was no predominance of exophytic,
      endophytic, or mixed tumor growth patterns. Extension of the tumor to
      extraretinal structures increased the mortality rate significantly.

PMID- 24877476
TI  - Introducing... Ophthalmic surgery, lasers & imaging.

PMID- 24877471
TI  - Corneal sensitivity in albinos.
AB  - The study reports measurements of corneal sensitivity in albino eyes obtained
      with a Cochet-Bonnet aesthesiometer. It was found to be much less sensitive (150%
      on average) than in a group of normal eyes. This result may have some bearing on
      the correction of albinos by contact lenses.

PMID- 24877478
TI  - Late-onset bacterial endophthalmitis following glaucoma drainage implantation.
AB  - Abstract. A clinicopathologic report of late-onset bacterial endophthalmitis 4
      years after implantation of a Baerveldt drainage implant is described. An 80
      yearold woman with glaucoma presented 8 years after tube shunt implantation with
      clinical endophthalmitis. During surgical removal of the implant, a small
      conjunctival buttonhole caused by the suture securing the plate to the sclera was
      noted to be the only entry site. Vitreous and anterior chamber taps were
      performed with intravitreal antibiotics. Cultures revealed Streptococcus
      pneumoniae infection. The pathologic analysis showed epithelialization of the
      conjunctival buttonhole and diffuse ocular inflammation, mucopurulent material,
      and fibrovascular membranes. Due to severe pain, the eye was enucleated after 1
      week. [Ophthalmic Surg Lasers Imaging 2003;34:128-130.]. 

PMID- 24877483
TI  - Saving lives: children's and adults'.

PMID- 24877479
TI  - Bilateral juxtapapillary subretinal neovascularization and pseudopapilledema in a
      three-year-old child.
AB  - A case of bilateral pseudopapilledema associated with serous and hemorrhagic
      detachment of the juxtapapillary sensory retina in a 35-month-old girl was
      thought to be secondary to optic nerve drusen.

PMID- 24877484
TI  - ADHD: collaboration on diagnosis and management among the medical home, school,
      and family.

PMID- 24877485
TI  - A 4-year-old girl with abdominal pain and fever.

PMID- 24877487
TI  - A 10-year-old boy with fever, sudden onset of lower back pain, and gait change.

PMID- 24877486
TI  - Tricky triggers of intertrigo.

PMID- 24877489
TI  - Acquired and congenital pediatric cardiac disease.

PMID- 24877488
TI  - An 11-year-old boy with diffuse pulmonary infiltrates and respiratory failure.

PMID- 24877490
TI  - Pediatric upper-extremity fractures.
AB  - Upper-extremity fractures account for more than half of childhood bony injuries.
      The frequency of injury increases with increasing mobility. The most common
      mechanism is a fall on an outstretched hand while playing. Optimal management
      requires knowledge of the normal anatomy and variants unique to pediatric bones.
      The physician needs to maintain a high level of suspicion for growth plate
      injuries because if unrecognized, these may result in growth arrest. Although the
      vast majority of pediatric upper-extremity fractures will heal rapidly with
      minimal intervention, physicians should be aware of the complications that can
      arise from these injuries. 

PMID- 24877491
TI  - A neonate with critical congenital heart disease.
AB  - Critical congenital heart disease (CCHD) is defined as a ductal-dependent
      congenital heart defect requiring surgical or percutaneous intervention via
      cardiac catheterization before 1 year of age. Most cases of CCHD can be diagnosed
      with prenatal ultrasound or fetal echocardiogram. If not prenatally diagnosed,
      CCHD can be stable in the newborn nursery due to persistent ductal patency, and
      the patient may only be diagnosed after ductal closure and development of cardiac
      symptoms at home. In this case, a 6-day-old female presented to the emergency
      department (ED) floppy with agonal respirations, poor capillary refill, and
      absent femoral pulses. On the day of presentation, the patient became
      increasingly fussy, refused feeding, and began to gasp. The patient was
      transported to the ED for evaluation, where a bedside echocardiogram revealed
      interrupted aortic arch (IAA), ventricular septal defect, minimal flow through a
      thread-like ductus arteriosus, and severely depressed cardiac function. IAA is
      very rare, with an incidence of three cases per 1 million live births. Patients
      require neonatal supportive care, continuous prostaglandin E1 infusion, and
      urgent referral for neonatal surgical repair in the first days to weeks of life.
      To reduce the volume of undiagnosed CCHD in the immediate newborn period, the
      U.S. Department of Health and Human Services Secretary's Advisory Committee on
      Heritable Diseases in Newborns and Children (SACHDNC) recommended that CCHD
      screening via pulse oximetry be added to the recommended uniform screening panel.
      A positive screen results in an immediate referral for an echocardiogram. Fetal
      diagnosis, newborn screening, and/or careful clinical examination may have
      resulted in detection of IAA in our patient prior to ductal closure. 

PMID- 24877493
TI  - A 16-year-old male with dizziness, parasthesias, and ataxia.
AB  - A 16-year-old African-American male with no past medical history presented with
      gait instability and somnolence. He had intermittent neurological complaints
      during the prior 4 months, including dizziness, left arm paresthesias, decreased
      hearing, and inability to control his hands. After an initial diagnosis of
      vertigo, his symptoms progressed, leading to reevaluation and a second emergency
      department head computed tomography (CT) scan, which revealed a large area of
      hypodensity in the cerebellum. Repeat head CT on arrival to the intensive care
      unit showed a large, left cerebellar hemispheric stroke. This case study
      discusses the findings of the patient's cerebral angiogram, the diagnosis of
      fibromuscular dysplasia, and the aggressive treatment that likely prevented
      further devastating strokes in the brainstem, thalamus, and occipital lobe. This
      case serves as a reminder that strokes are not just an adult disease and that
      classic presentations can occur even in unconventional patients. 

PMID- 24877492
TI  - A 12-week-old male with a 10-day history of fever.
AB  - Kawasaki disease (KD) is a self-limited vasculitis that can have significant
      morbidity and even mortality if not identified and treated early. The purpose of
      this case study is to highlight the importance of keeping KD in the differential
      diagnosis, even if all clinical criteria are not met. This is especially true in
      children younger than 1 year of age, who are more likely to have an incomplete or
      atypical presentation. The patient in this study is a 12-week-old African
      American male with no significant past medical history who presented with a 10
      day history of fever up to 105 degrees  F. An echocardiogram shortly after
      admission demonstrated normal cardiac structure and function with evidence of
      coronary artery abnormalities. Diagnosis of KD (treatment with intravenous
      immunoglobulin, aspirin, and a tumor necrosis factor-alpha inhibitor) and follow
      up imaging are detailed. Treatment of KD in the acute phase is aimed at
      preventing coronary thrombosis and aneurysm formation.

PMID- 24877497
TI  - Retina and optic nerve imaging.

PMID- 24877494
TI  - An unusual cause of respiratory distress in an infant.
AB  - Partial anomalous venous connection (PAPVC) is a congenital cardiovascular defect
      where one or more (but not all) of the pulmonary veins return anomalously back to
      the right atrium, either via a direct or indirect connection. It often occurs
      with other cardiac defects, most commonly a secundum atrial septal defect.
      Individuals with a large degree of shunting will present with dyspnea, fatigue,
      and, in some cases, heart failure. Clinical associations and variants of PAPVC
      include scimitar syndrome, pseudo-scimitar or meandering right pulmonary vein,
      sinous venosus defects, malposition of the septum primum, and Turner syndrome.
      The patient in this case, a previously healthy, 6-month-old, full-term male,
      presented to the emergency department for evaluation of respiratory distress and
      wheezing. The infant was first seen in his pediatrician's office, where he was
      noted to be tachypneic and wheezing. He was feeding without difficulty, voiding
      well, and was active and playful. The patient had passed critical congenital
      heart disease screening after his birth and prior to discharge, and the family
      history was negative for any respiratory or cardiac conditions. Cardiac magnetic
      resonance imaging is becoming the mode of choice for diagnosis of PAPVC. The
      definitive treatment is surgical correction, but surgery is not indicated in all
      cases, especially if the patient is asymptomatic and the degree of shunting is
      small. Patients with isolated PAPVC who undergo surgical correction have good
      long-term outcomes. In this case, the patient underwent the Warden procedure,
      which causes an increased risk of superior vena cava stenosis or obstruction to
      the right atrium. This patient will require lifelong follow-up to assess for new
      onset pulmonary venous obstruction. 

PMID- 24877502
TI  - What I know for sure: the value of interprofessional education and practice in
      geriatrics and an exciting new collaboration for our journal.

PMID- 24877511
TI  - Retina, choroid, and vitreous: the requisites in ophthalmology, first edition.

PMID- 24877513
TI  - CATARACT SURGERY: TECHNIQUE, COMPLICATIONS, AND MANAGEMENT, 2nd ed.

PMID- 24877522
TI  - Practice management issues.

PMID- 24877523
TI  - Facial rash. . .with vision loss and bilateral retinopathy.

PMID- 24877524
TI  - Faster than a speeding bullet, more powerful than a locomotive...but much more
      precise!

PMID- 24877525
TI  - Effect of four-muscle tenotomy and reattachment on fusion maldevelopment
      nystagmus syndrome.

PMID- 24877527
TI  - Propranolol and periocular capillary hemangiomas: assessment of refractive
      effect.
AB  - PURPOSE: To assess the effects of systemic propranolol on refractive error in
      infants with periocular capillary hemangiomas. METHODS: A single-center study of
      consecutive patients with capillary hemangiomas treated with systemic
      propranolol. Refractive data were analyzed using Long's matrix formalism and the
      methods of Harris and Kaye. RESULTS: Seventeen patients were included. At 6
      months postoperatively, hemangioma size reduced from 3,214 to 1,806 mm(3)
      (standard deviation: 4,122 to 2,441). Mean refractive error in the affected eye
      significantly reduced: -1.25/0.38 * 36 (95% confidence intervals: -5.08/1.20 * 90
      to 1.64/1.43 * 180, P = .048) with a smaller change (P = .06) in the unaffected
      eye of -1.01/+0.31 * 3.16 (95% confidence intervals: -4.02/+1.12 * 180 to
      +1.49/+0.51 * 90). CONCLUSIONS: Propranolol produced a clinically significant
      reduction in the infants' refractive error and anisometropia. The reduction in
      the total refractive error and anisometropia has not been evident in previous
      analyses, which have concentrated on the change in the "cylinder" as the
      principal outcome measure.

PMID- 24877526
TI  - Pediatric infectious endophthalmitis: a review.
AB  - Infectious endophthalmitis is a rare but severe complication of septecemia,
      intraocular surgeries, or penetrating eye trauma. The etiology, prognosis, and
      management of pediatric endophthalmitis resulting from exogenous and endogenous
      infections are reviewed. Open-globe trauma and glaucoma surgery are the most
      frequent causes of endophthalmitis in children, whereas endogenous infection is
      the least common cause. Streptococcus and Staphylococcus species are common
      bacterial agents in both posttraumatic and postoperative pediatric
      endophthalmitis, whereas Candida albicans is a commonly reported organism in
      endogenous endophthalmitis. Additionally, Streptococcus pneumoniae and
      Haemophilus influenzae appear more likely as pathogens in children than in
      adults. The clinical manifestations and outcome usually correlate with the
      virulence of the infecting organism. The visual prognosis of endophthalmitis is
      generally poor.

PMID- 24877528
TI  - Congenital eyelid eversion.

PMID- 24877530
TI  - Ophthalmic photography: retinal photography, angiography, and electronic imaging,
      second edition.

PMID- 24877532
TI  - Pediatric cataract surgery: techniques, complications, and management.

PMID- 24877535
TI  - Photodynamic therapy of ocular diseases.

PMID- 24877544
TI  - Ocular pathology, 5th edition.

PMID- 24877537
TI  - Handbook of optical coherence tomography.

PMID- 24877548
TI  - Acute and critical care nurses' perceptions of palliative care competencies: a
      pilot study.
AB  - Competency development among acute and critical care nurses has focused primarily
      on the provision of life-sustaining care and less on the care of patients who
      fail to respond to life-prolonging treatments. Examining nurses' beliefs,
      perceptions, and experiences with patients' palliative care needs may improve
      continuing education programs, practice resources, educational curricula, and
      professional nursing practice. Survey methodology was used to conduct this pilot
      study. Forty-nine nurses completed a 33-item survey instrument in 2012.
      Respondents consisted of nurses attending a critical care continuing education
      event and graduate nursing students in an acute care nurse practitioner program.
      Statistical tests were used to examine differences in perceived importance of
      core competencies in palliative care. Findings from this study demonstrate
      variation in palliative care knowledge and perceived relative importance of core
      competencies needed in palliative care practice. This study provides preliminary
      data about knowledge differences among different nursing groups and a foundation
      for further study.

PMID- 24877549
TI  - Outcomes of a quality improvement project for educating nurses on medication
      administration and errors in nursing homes.
AB  - BACKGROUND: The Institute of Medicine has provided recommendations for preventing
      medication errors in nursing homes that include nursing education. Support for
      education on medication administration is derived from evidence, primarily in
      settings other than nursing homes. This quality improvement project implemented
      an educational program for licensed nurses to increase knowledge of medication
      administration and to decrease medication-related errors. METHOD: A descriptive
      study of 72 licensed nurses in two nursing homes was used for this project.
      Medication resources were provided at nursing stations in both facilities.
      Licensed nurses took a pretest and then watched a 35-minute education
      presentation. One month later, they took a posttest. RESULTS: Percentage scores
      on the tests were calculated. Paired t tests demonstrated an increase in nursing
      knowledge in one facility (p = 0.04) and no significant increase in nursing
      knowledge in the second. CONCLUSION: Mandatory participation by all staff members
      who administer medications would increase participation in the project. Multiple
      factors influence knowledge and medication administration in nursing homes and
      need further study.

PMID- 24877550
TI  - Providing 360-degree multisource feedback to nurse educators in the country of
      Georgia: a formative evaluation of acceptability.
AB  - BACKGROUND: Due to insufficient nursing education standards in the country of
      Georgia, 15 health professionals participated in a USAID grant-funded nurse
      educator faculty development program. These educators then offered continuing
      education courses and taught more than 1,700 practicing Georgian nurses over 3
      years. METHOD: Using a 360-degree multisource feedback model (MSF), self, video,
      learner, peer, and program coordinator evaluations of teaching effectiveness were
      completed. After nurse educators reviewed their results and identified areas for
      improvement, a questionnaire about the perceived acceptability of teacher
      evaluations was completed. RESULTS: Of the 15 nurse educators, 93.3% indicated
      that nurse educators should receive feedback through self, learner, peer, and
      video evaluations, and 100% indicated that nurse educators should receive
      feedback from the program coordinator. The accuracy and usefulness of the program
      coordinator evaluation was rated the highest, whereas peer evaluation was rated
      the lowest. CONCLUSION: This study revealed that MSF was acceptable to Georgian
      nurse educators.

PMID- 24877551
TI  - Scheimpflug imaging for long-term evaluation of optical components in Hungarian
      children with a history of preterm birth.
AB  - PURPOSE: To determine ocular geometry and refraction in children with a history
      of preterm birth, and compare them to age-matched full-term children. METHODS: In
      a prospective case-control study, 50 eyes of 27 premature patients 7 to 14 years
      of age were evaluated with Scheimpflug camera after cycloplegia. Age-matched full
      term children comprised the control group (68 eyes of 34 children). All of the
      eligible eyes had a normal-appearing posterior pole. Anterior segment parameters
      such as keratometry, anterior chamber volume or thickness, and lens thickness
      were measured. Corneal thickness, lower- and higher-order aberrations refractive
      errors of the cornea (root mean square of lower- and higher-order aberrations:
      RMS LOA, RMS HOA) were also assessed and exported for further analysis. RESULTS:
      In the premature eyes, anterior chamber depth was marginally smaller (P = .06),
      the lens was significantly thicker (P = .03), and axial length was significantly
      shorter (P < .001). Scheimpflug imaging showed a significant difference in
      corneal RMS (P = .03) and an increase in corneal RMS HOA (P = .002) in the
      premature group. Preterm birth showed significant impact on axial length (P <
      .01) and lens thickness (P = .05); at the same time, anterior chamber depth was
      more influenced by retinopathy of prematurity stage (P = .01). Laser treatment
      showed marginally significant impact (P = .06) on anterior chamber depth.
      CONCLUSIONS: In premature eyes with or without mild retinopathy of prematurity,
      anterior segment anatomy is slightly different and they have more higher-order
      corneal aberrations compared to the eyes of term-born children.

PMID- 24877553
TI  - Ocular biomechanical metrics by CorVis ST in healthy Brazilian patients.
AB  - PURPOSE: To evaluate ocular biomechanical metrics given by the CorVis ST (Oculus,
      Inc., Berlin, Germany) in a population of healthy Brazilian patients. METHODS: An
      observational and cross-sectional study involving 1 eye randomly selected from 90
      healthy patients. Studied parameters (including deformation amplitude, first
      applanation time, highest concavity time, second applanation time, first
      applanation length, second applanation length, curvature radius highest
      concavity, curvature radius normal, velocity in, and velocity out) derived from
      the CorVis ST were correlated to central corneal thickness from the Pentacam
      (Oculus, Inc.). Differences between data on the basis of gender were evaluated.
      RESULTS: Mean patient age was 35.80 +/- 12.83 years (range: 21.07 to 78.84
      years). Mean central corneal thickness was 547.50 +/- 32.00 MUm (range: 490 to
      647 MUm) and mean spherical equivalent refraction was -3.29 +/- 3.69 diopters
      (range: -9.50 to +10.37 diopters). Mean deformation amplitude was 1.05 +/- 0.08
      mm (range: 0.91 to 1.26 mm). Highest concavity time was 18.38 +/- 0.93 ms (range:
      16.95 to 21.07 ms). Intraocular pressure was 16.43 +/- 2.15 mm Hg (range: 11.50
      to 21.0 mm Hg). First applanation time was 8.32 +/- 0.33 ms (range: 7.53 to 9.12
      ms) and second applanation time was 23.80 +/- 0.44 ms (range: 22.76 to 24.95 ms).
      First applanation length (max) was 2.07 +/- 0.38 mm (range: 1.20 to 3.10 mm) and
      second applanation length (max) was 2.37 +/- 0.47 mm (range: 1.33 to 4.12 mm).
      Curvature radius highest concavity was 11.09 +/- 2.06 mm (range: 7.58 to 15.98
      mm) and curvature radius normal was 7.59 +/- 0.67 mm (range: 6.82 to 11.02 mm).
      Velocity in was 0.21 +/- 0.05 m/s (range: 0.16 to 0.72 m/s) and velocity out was 
      0.33 +/- 0.07 m/s (range: -0.72 to -0.20 m/s). Studied parameters were not
      associated with gender. CONCLUSIONS: Eight of 11 ocular biomechanical metrics
      given by the CorVis ST were associated with central corneal thickness, but the
      influence of central corneal thickness on these measurements was low.

PMID- 24877554
TI  - Femtosecond laser-assisted MyoRing implantation in postoperative LASIK ectasia.
AB  - PURPOSE: To evaluate the effect of MyoRing implantations (DIOPTEX GmbH, Linz,
      Austria) in patients with ectasia after LASIK. METHODS: MyoRing implantation was
      performed in 15 eyes of 14 patients with ectasia after LASIK using a femtosecond
      laser. Uncorrected and corrected distance visual acuity, refraction, keratometry,
      central corneal thickness, corneal biomechanical profile, and corneal aberrometry
      were evaluated preoperatively and at 1, 3, and 6 months, and 1 year
      postoperatively. RESULTS: Uncorrected distance visual acuity (1.02 +/- 0.48 to
      0.30 +/- 0.18 logMAR), maximum keratometry (50.14 +/- 1.82 to 43.80 +/- 1.21
      diopters), and sphere (-4.4 +/- 4.8 to +1.50 +/- 0.61 diopters) were
      significantly improved from preoperative values at 1 month after surgery with no
      significant change afterward. Corrected distance visual acuity did not improve
      significantly 1 month after implantation, but between the 1- and 3-month follow
      up visits, a significant improvement (0.30 +/- 0.1 to 0.17 +/- 0.13 logMAR) was
      observed without any additional improvement thereafter. A nearly significant (P =
      .05) increase in central corneal thickness (439.4 +/- 19 to 452.2 +/- 20 MUm) was
      observed during the 1-month postoperative period. Primary coma, higher-order
      aberrations, and trefoil showed an insignificant decrease 1 month after surgery
      and afterward. Spherical aberration significantly increased between the
      preoperative visit and the first postoperative visit. Corneal hysteresis and
      corneal resistance factor showed no significant change between visits.
      CONCLUSIONS: MyoRing is a safe and effective method in patients with ectasia
      after LASIK. It can improve corrected distance visual acuity and reduce
      refractive error in these patients.

PMID- 24877556
TI  - A molecular iron catalyst for the acceptorless dehydrogenation and hydrogenation
      of N-heterocycles.
AB  - A well-defined iron complex (3) supported by a bis(phosphino)amine pincer ligand
      efficiently catalyzes both acceptorless dehydrogenation and hydrogenation of N
      heterocycles. The products from these reactions are isolated in good yields.
      Complex 3, the active catalytic species in the dehydrogenation reaction, is
      independently synthesized and characterized, and its structure is confirmed by X
      ray crystallography. A trans-dihydride intermediate (4) is proposed to be
      involved in the hydrogenation reaction, and its existence is verified by NMR and
      trapping experiments. 

PMID- 24877557
TI  - Symmetry and coplanarity of organic molecules affect their packing and
      photovoltaic properties in solution-processed solar cells.
AB  - In this study we synthesized three acceptor-donor-acceptor (A-D-A) organic
      molecules, TB3t-BT, TB3t-BTT, and TB3t-BDT, comprising 2,2'-bithiophene (BT),
      benzo[1,2-b:3,4-b':5,6-d"]trithiophene (BTT), and benzo[1,2-b;4,5-b']dithiophene
      (BDT) units, respectively, as central cores (donors), terthiophene (3t) as pi
      conjugated spacers, and thiobarbituric acid (TB) units as acceptors. These
      molecules display different degrees of coplanarity as evidenced by the
      differences in dihedral angles calculated from density functional theory. By
      using differential scanning calorimetry and X-ray diffractions for probing their
      crystallization characteristics and molecular packing in active layers, we found
      that the symmetry and coplanarity of molecules would significantly affect the
      melting/crystallization behavior and the formation of crystalline domains in the
      blend film with fullerene, PC61BM. TB3t-BT and TB3t-BDT, which each possess an
      inversion center and display high crystallinity in their pristine state, but they
      have different driving forces in crystallization, presumably because of different
      degrees of coplanarity. On the other hand, the asymmetrical TB3t-BTT behaved as
      an amorphous material even though it possesses a coplanar structure. Among our
      tested systems, the device comprising as-spun TB3t-BDT/PC61BM (6:4, w/w) active
      layer featured crystalline domains and displayed the highest power conversion
      efficiency (PCE) of 4.1%. In contrast, the as-spun TB3t-BT/PC61BM (6:4, w/w)
      active layer showed well-mixed morphology and with a device PCE of 0.2%; it
      increased to 3.9% after annealing the active layer at 150  degrees C for 15 min.
      As for TB3t-BTT, it required a higher content of fullerene in the TB3t-BTT/PC61BM
      (4:6, w/w) active layer to optimize its device PCE to 1.6%. 

PMID- 24877559
TI  - Poly(glycerol sebacate urethane)-cellulose nanocomposites with water-active shape
      memory effects.
AB  - Biodegradable and biocompatible materials with shape-memory effects (SMEs) are
      attractive for use as minimally invasive medical devices. Nanocomposites with
      SMEs were prepared from biodegradable poly(glycerol sebacate urethane) (PGSU) and
      renewable cellulose nanocrystals (CNCs). The effects of CNC content on the
      structure, water absorption, and mechanical properties of the PGSU were studied.
      The water-responsive mechanically adaptive properties and shape-memory
      performance of PGSU-CNC nanocomposites were observed, which are dependent on the
      content of CNCs. The PGSU-CNC nanocomposite containing 23.2 vol % CNCs exhibited
      the best SMEs among the nanocomposites investigated, with the stable shape fixing
      and shape recovery ratios being 98 and 99%, respectively, attributable to the
      formation of a hydrophilic, yet strong, CNC network in the elastomeric matrix. In
      vitro degradation profiles of the nanocomposites were assessed with and without
      the presence of an enzyme. 

PMID- 24877558
TI  - Focal activation of cells by plasmon resonance assisted optical injection of
      signaling molecules.
AB  - Experimental methods for single cell intracellular delivery are essential for
      probing cell signaling dynamics within complex cellular networks, such as those
      making up the tumor microenvironment. Here, we show a quantitative and general
      method of interrogation of signaling pathways. We applied highly focused near
      infrared laser light to optically inject gold-coated liposomes encapsulating
      bioactive molecules into single cells for focal activation of cell signaling. For
      this demonstration, we encapsulated either inositol trisphosphate (IP3), an
      endogenous cell signaling second messenger, or adenophostin A (AdA), a potent
      analogue of IP, within 100 nm gold-coated liposomes, and injected these gold
      coated liposomes and their contents into the cytosol of single ovarian carcinoma
      cells to initiate calcium (Ca(2+)) release from intracellular stores. Upon
      optical injection of IP3 or AdA at doses above the activation threshold, we
      observed increases in cytosolic Ca(2+) concentration within the injected cell
      initiating the propagation of a Ca(2+) wave throughout nearby cells. As confirmed
      by octanol-induced inhibition, the intercellular Ca(2+) wave traveled via gap
      junctions. Optical injection of gold-coated liposomes represents a quantitative
      method of focal activation of signaling cascades of broad interest in biomedical
      research. 

PMID- 24877560
TI  - Targeting to endothelial cells augments the protective effect of novel dual
      bioactive antioxidant/anti-inflammatory nanoparticles.
AB  - Oxidative stress and inflammation are intertwined contributors to numerous acute
      vascular pathologies. A novel dual bioactive nanoparticle with antioxidant/anti
      inflammatory properties was developed based on the interactions of tocopherol
      phosphate and the manganese porphyrin SOD mimetic, MnTMPyP. The size and drug
      incorporation efficiency were shown to be dependent on the amount of MnTMPyP
      added as well as the choice of surfactant. MnTMPyP was shown to retain its SOD
      like activity while in intact particles and to release in a slow and controlled
      manner. Conjugation of anti-PECAM antibody to the nanoparticles provided
      endothelial targeting and potentiated nanoparticle-mediated suppression of
      inflammatory activation of these cells manifested by expression of VCAM, E
      selectin, and IL-8. This nanoparticle technology may find applicability with drug
      combinations relevant for other pathologies. 

PMID- 24877561
TI  - Leptin induces hippocampal synaptogenesis via CREB-regulated microRNA-132
      suppression of p250GAP.
AB  - Leptin acts in the hippocampus to enhance cognition and reduce depression and
      anxiety. Cognitive and emotional disorders are associated with abnormal
      hippocampal dendritic spine formation and synaptogenesis. Although leptin has
      been shown to induce synaptogenesis in the hypothalamus, its effects on
      hippocampal synaptogenesis and the mechanism(s) involved are not well understood.
      Here we show that leptin receptors (LepRs) are critical for hippocampal dendritic
      spine formation in vivo because db/db mice lacking the long form of the leptin
      receptor (LepRb) have reduced spine density on CA1 and CA3 neurons. Leptin
      promotes the formation of mature spines and functional glutamate synapses on
      hippocampal pyramidal neurons in both dissociated and slice cultures. These
      effects are blocked by short hairpin RNAs specifically targeting the LepRb and
      are absent in cultures from db/db mice. Activation of the LepR leads to cAMP
      response element-binding protein (CREB) phosphorylation and initiation of CREB
      dependent transcription via the MAPK kinase/Erk pathway. Furthermore, both
      Mek/Erk and CREB activation are required for leptin-induced synaptogenesis.
      Leptin also increases expression of microRNA-132 (miR132), a well-known CREB
      target, which is also required for leptin-induced synaptogenesis. Last, leptin
      suppresses the expression of p250GAP, a miR132 target, and this suppression is
      obligatory for leptin's effects as is the downstream target of p250GAP, Rac1.
      LepRs appear to be critical in vivo as db/db mice have lowered hippocampal miR132
      levels and elevated p250GAP expression. In conclusion, we identify a novel
      signaling pathway by which leptin increases synaptogenesis through inducing CREB
      transcription and increasing microRNA-mediated suppression of p250GAP activity,
      thus removing a known inhibitor of Rac1-stimulated synaptogenesis. 

PMID- 24877563
TI  - PKClambda haploinsufficiency prevents diabetes by a mechanism involving
      alterations in hepatic enzymes.
AB  - Tissue-specific knockout (KO) of atypical protein kinase C (aPKC), PKC-lambda,
      yields contrasting phenotypes, depending on the tissue. Thus, whereas muscle KO
      of PKC-lambda impairs glucose transport and causes glucose intolerance, insulin
      resistance, and liver-dependent lipid abnormalities, liver KO and adipocyte KO of
      PKC-lambda increase insulin sensitivity through salutary alterations in hepatic
      enzymes. Also note that, although total-body (TB) homozygous KO of PKC-lambda is
      embryonic lethal, TB heterozygous (Het) KO (TBHetlambdaKO) is well-tolerated.
      However, beneath their seemingly normal growth, appetite, and overall appearance,
      we found in TBHetlambdaKO mice that insulin receptor phosphorylation and
      signaling through insulin receptor substrates to phosphatidylinositol 3-kinase,
      Akt and residual aPKC were markedly diminished in liver, muscle, and adipose
      tissues, and glucose transport was impaired in muscle and adipose tissues.
      Furthermore, despite these global impairments in insulin signaling, other than
      mild hyperinsulinemia, glucose tolerance, serum lipids, and glucose disposal and
      hepatic glucose output in hyperinsulinemic clamp studies were normal. Moreover,
      TBHetlambdaKO mice were protected from developing glucose intolerance during high
      fat feeding. This metabolic protection (in the face of impaired insulin
      signaling) in HetlambdaKO mice seemed to reflect a deficiency of PKC-lambda in
      liver with resultant 1) increases in FoxO1 phosphorylation and decreases in
      expression of hepatic gluconeogenic enzymes and 2) diminished expression of
      hepatic lipogenic enzymes and proinflammatory cytokines. In keeping with this
      postulate, adenoviral-mediated supplementation of hepatic PKC-lambda induced a
      diabetic state in HetlambdaKO mice. Our findings underscore the importance of
      hepatic PKC-lambda in provoking abnormalities in glucose and lipid metabolism. 

PMID- 24877562
TI  - Human endometrial DNA methylome is cycle-dependent and is associated with gene
      expression regulation.
AB  - Human endometrium undergoes major gene expression changes, resulting in altered
      cellular functions in response to cyclic variations in circulating estradiol and
      progesterone, largely mediated by transcription factors and nuclear receptors. In
      addition to classic modulators, epigenetic mechanisms regulate gene expression
      during development in response to environmental factors and in some diseases and
      have roles in steroid hormone action. Herein, we tested the hypothesis that DNA
      methylation plays a role in gene expression regulation in human endometrium in
      different hormonal milieux. High throughput, genome-wide DNA methylation
      profiling of endometrial samples in proliferative, early secretory, and
      midsecretory phases revealed dynamic DNA methylation patterns with segregation of
      proliferative from secretory phase samples by unsupervised cluster analysis of
      differentially methylated genes. Changes involved different frequencies of gain
      and loss of methylation within or outside CpG islands. Comparison of changes in
      transcriptomes and corresponding DNA methylomes from the same samples revealed
      association of DNA methylation and gene expression in a number of loci, some
      important in endometrial biology. Human endometrial stromal fibroblasts treated
      in vitro with estradiol and progesterone exhibited DNA methylation changes in
      several genes observed in proliferative and secretory phase tissues,
      respectively. Taken together, the data support the observation that epigenetic
      mechanisms are involved in gene expression regulation in human endometrium in
      different hormonal milieux, adding endometrium to a small number of normal adult
      tissues exhibiting dynamic DNA methylation. The data also raise the possibility
      that the interplay between steroid hormone and methylome dynamics regulates
      normal endometrial functions and, if abnormal, may result in endometrial
      dysfunction and associated disorders. 

PMID- 24877564
TI  - Maternal thyroid hormones are essential for neural development in zebrafish.
AB  - Teleost eggs contain an abundant store of maternal thyroid hormones (THs), and
      early in zebrafish embryonic development, all the genes necessary for TH
      signaling are expressed. Nonetheless the function of THs in embryonic development
      remains elusive. To test the hypothesis that THs are fundamental for zebrafish
      embryonic development, an monocarboxilic transporter 8 (Mct8) knockdown strategy
      was deployed to prevent maternal TH uptake. Absence of maternal THs did not
      affect early specification of the neural epithelia but profoundly modified later
      dorsal specification of the brain and spinal cord as well as specific neuron
      differentiation. Maternal THs acted upstream of pax2a, pax7, and pax8 genes but
      downstream of shha and fgf8a signaling. The lack of inhibitory spinal cord
      interneurons and increased motoneurons in the mct8 morphants is consistent with
      their stiff axial body and impaired mobility. The mct8 mutations are associated
      with X-linked mental retardation in humans, and the cellular and molecular
      consequences of MCT8 knockdown during embryonic development in zebrafish provides
      new insight into the potential role of THs in this condition. 

PMID- 24877566
TI  - Pharmacophore modeling technique applied for the discovery of proteasome
      inhibitors.
AB  - INTRODUCTION: The 26S proteasome has many important roles in the biological
      functions of the cells, and proteasome inhibitors have multiple and complex
      activities on cells. These compounds can be natural or synthesized. Most
      synthetic derivatives have been rationally designed, synthesized and optimized to
      obtain the best selectivity and increase the activity. The design of chemical
      entities with desired molecular identification, which plays an important role in
      biological systems, is provided by pharmacophore modeling. Indeed, pharmacophore
      models can be established either in a ligand-based manner or in a receptor-based
      manner. AREAS COVERED: The authors discuss the application of pharmacophore
      modeling techniques to proteasome inhibitors development. Furthermore, the
      article reviews the classification of the currently discovered proteasome
      inhibitors where the principal mechanism of action and clinical application are
      represented. EXPERT OPINION: In the era of new drug development, database of
      compounds should be thoroughly evaluated with a combination of methods that
      consider both pharmacophore- and ligand-based virtual screening. The concept of
      pharmacophore helps to discover new active compounds and to evaluate their
      activity. The nature of proteasome inhibitor pharmacophore affects the secondary
      active-site specificity; indeed, increasing specificity decreases the
      cytotoxicity of the proteasome inhibitors. It is hypothesized that the balanced
      simultaneous modulation of a few druggable targets may have superior efficacy and
      fewer side effects than single-target or combination therapies for the treatment
      of human cancers. The discovery of new compounds should aim to find more active
      compounds that improve the compliance of patients.

PMID- 24877567
TI  - Rationale, methodology, implementation, and first results of the French out-of
      hospital cardiac arrest registry.
AB  - INTRODUCTION: Out-of-hospital cardiac arrest (OHCA) is an important public health
      issue with an estimated incidence of 50,000 cases per year in France. Community
      survival rates for OHCA are still low (approximately 5%). An effective,
      recognized way to study, assess, and improve OHCA care is to create a standard
      format database. OBJECTIVE: The aim of this work is to present the French OHCA
      registry (ReAC). METHODS: ReAC is a secure, web-based data management system that
      was initiated in 2009 and deployed nationally in June 2012. The main goal of this
      registry is to improve the care and survival rate of OHCA patients. The survey
      form is in compliance with the requirements of French organizations and is
      organized in accordance with the Utstein universal style. ReAC provides real-time
      statistical analyses and enables all French mobile emergency and resuscitation
      services (MERS) to assess and improve their professional OHCA care practices.
      RESULTS: In June 2012, the ReAC was nationally opened for all French MERSs. In
      June 2013, 221 of a possible 320 MERS participated in the ReAC. A total of 15,944
      OHCA have been collected (14,939 cases closed with follow-up monitoring). The
      current rate of inclusion is approximately 1,500 cases per month. Since August
      2012, the inclusion rate has increased by 9.5% per month, while the participation
      rate has increased by 9% per month. The first results show that the population is
      mainly male (65.4%) and the mean age is 65 +/- 19 years. On MERS arrival, 73.5%
      of the patients were in asystole. The rates of return of spontaneous circulation,
      survival to hospital admission, and 30-day survival are low (respectively 21.1%,
      17.2%, 4.6%). Of those who survived 30 days, 84.0% had a good neurological
      recovery. CONCLUSIONS: The ReAC registry is a reliable observation tool to
      improve public health management of OHCA. It provides relevant information to
      adapt or to develop diagnosis, treatments, and prognostic resources. Moreover, it
      enables the development of targeted awareness programs for the unique purpose of
      increasing the survival rates of OHCA patients.

PMID- 24877570
TI  - [Life destiny, work context, illness coping and psychosomatic psychotherapeutic
      treatment possibilities].

PMID- 24877565
TI  - The osteoblast to osteocyte transition: epigenetic changes and response to the
      vitamin D3 hormone.
AB  - Osteocytes are derived from osteoblast lineage cells that become progressively
      embedded in mineralized bone. Development of the osteocytogenic cell line IDG-SW3
      has enabled a temporal and mechanistic investigation of this process. Through RNA
      sequencing analyses, we show that although substantial changes in gene expression
      occur during the osteoblast to osteocyte transition, the majority of the
      transcriptome remains qualitatively osteoblast like. Genes either up-regulated or
      expressed uniquely in the osteocyte include local and systemic factors such as
      Sost and Fgf23 as well as genes implicated in neuronal, muscle, vascular, or
      regulatory function. As assessed by chromatin immunoprecipitation coupled to high
      throughput sequencing, numerous changes in epigenetic histone modifications also
      occur during osteocytogenesis; these are largely qualitative rather than
      quantitative. Specific epigenetic changes correlate with altered gene expression
      patterns that are observed during the transition. These genomic changes likely
      influence the highly restricted transcriptomic response to 1,25(OH)(2)D(3) that
      occurs during differentiation. VDR binding in osteocytes revealed an extensive
      cistrome co-occupied by retinoid X receptor and located predominantly at sites
      distal to regulated genes. Although sites of VDR binding were apparent near many
      1,25(OH)(2)D(3)-regulated genes, the expression of others adjacent to VDR-binding
      sites were unaffected; lack of VDR binding was particularly prevalent at down
      regulated genes. Interestingly, 1,25(OH)(2)D(3) was found to induce the Boc and
      Cdon coreceptors that are active in hedgehog signaling in osteocytes. We conclude
      that osteocytogenesis is accompanied by changes in gene expression that may be
      driven by both genetic and epigenetic components. These changes are likely
      responsible for the osteocyte phenotype and may contribute to reduced sensitivity
      to 1,25(OH)(2)D(3).

PMID- 24877571
TI  - [Non-response to therapy in acute and rehabilitative psychosomatic inpatient care
      - a systematic review].
AB  - OBJECTIVES: The study reviews the state-of-the art on failure research in acute
      and rehabilitative psychosomatic inpatient care. The main focus of interest lies
      in describing the frequency and possible predictors of unsuccessful therapeutic
      treatments. METHODS: We systematically searched the databases MEDLINE,
      PsycARTICLES, PsycINFO und PSYNDEX and selected studies from the past 20 years
      focusing on treatment failure in the inpatient psychosomatic treatment of adult
      patients. RESULTS: A total of 31 studies were included, 15 of which allowed the
      extraction of predictors of non-response or deterioration. 20 %to 30%of patients
      leave psychotherapeutic treatment without any significant change; 5 %to
      10%deteriorate during their stay.A high level of symptom distress at intake, a
      chronic course of the disease as well as somatoform or personality disorders are
      associated with non-response and deterioration. Early response to treatment and a
      dysfunctional therapeutic alliance are possible further predictors, whereas
      sociodemographic and sociomedical variables are unlikely to have a predictive
      validity. CONCLUSIONS: Hypotheses about possible predictors can be derived from
      the results of this review. However, the interpretation of the results is limited
      by the heterogeneity of the methodology and of the samples of the studies
      included. Nevertheless the results can be used as a basis for further hypothesis
      driven research.

PMID- 24877572
TI  - [Trauma, developmental stages, and motivational abilities in indentured Swiss
      child laborers in old age].
AB  - OBJECTIVES: The study examined the relationship between potential traumatic
      events in childhood and motivational abilities in old adulthood according to
      developmental stage. METHODS: The motivational abilities of self-efficacy,
      conscientiousness and impulsivity (self control) were investigated in a sample of
      114 formerly indentured Swiss child laborers. Adversities were assessed by the
      Childhood Trauma Questionnaire (CTQ). The sample was split into four age groups
      according to the beginning of the potential trauma: infancy (0-2), preschool (3
      5), early childhood (6-9), and early adolescence (>= 10). RESULTS: The strongest
      relationship was found between self-efficacy and CTQ in the group "early
      adolescence," followed by the relationship between conscientiousness and CTQ in
      the same group. Impulsivity and CTQ were most strongly associated in the
      "preschool" group. CONCLUSION: Childhood adversities seem to have a negative
      impact on self-efficacy and conscientiousness after the age of ten. In contrast,
      self-control seems to be affected by the deleterious effect of trauma or
      adversity already at an earlier age.

PMID- 24877573
TI  - [The self-concept of patients with Social Anxiety Disorder: manifestation and
      change through psychotherapy ].
AB  - OBJECTIVES: To determine whether the self-concept of patients with Social Anxiety
      Disorder deviates significantly from that found in the normative sample, to what
      extent it changes through psychotherapeutic short-term interventions and how such
      changes in self-concept relate to changes in the level of social anxiety.
      METHODS: The self-concept of N = 86 patients with Social Anxiety Disorder was
      assessed using the Frankfurter-Selbstkonzeptskalen (FSKN; Deusinger 1986).
      Patients were treated with a manualized cognitive (CT) or psychodynamic (PDT)
      short-term intervention. The level of social anxiety was assessed pre-therapy and
      post-therapy via the Liebowitz Social Anxiety Scale (Stangier & Heidenreich 2004)
      and the Social Phobia and Anxiety Scale (Fydrich 2002). RESULTS: Patients with
      Social Anxiety Disorder exhibited a significantly more negative self-concept than
      the norm (all ps0.001). Their self-concept improved significantly in all facets
      following psychotherapeutic short-term intervention (all ps0.01). No significant
      difference was found between cognitive and psychodynamic therapy. Improvements in
      self-concept correlate with reductions in social anxiety. CONCLUSIONS: The
      results confirm the relevance of self-concept in Social Anxiety Disorder and its
      susceptibility to short-term-therapy.

PMID- 24877574
TI  - [Treatment of psychosomatic disorders occurring in the vocational context -
      concept and first findings ].
AB  - OBJECTIVES: Psychosomatic symptoms often present within the vocational context.
      The unmet need for easily accessible and early interventions led to the
      development of a variety of offers in this area. From a scientific point of view,
      the question of how such a "psychosomatic consultation in the workplace" (PCIW)
      is best conceptualized remains open. METHODS: We analysed treatment documentation
      for all patients of two recently established PCIW from January 2011 to January
      2012 both descriptively and by qualitative content analysis. RESULTS: A total of
      67 patients were seen, 75% of whom were male. For 75% of users PCIW constituted
      the first contact with psychosomatic-psychotherapeutic-psychiatric services. For
      about 80%of the patients a work-related aetiology could be considered. 40%of
      patients were recommended to outpatient psychotherapeutic care. CONCLUSIONS: PCIW
      represents an easily accessible therapeutic offer in the vocational context.
      There often is a mix of work-related and personal problems that suggests the
      cooperation of occupational and psychosomatic physicians.

PMID- 24877575
TI  - Assessing psychosocial vulnerability and care needs of pretransplant patients by
      means of the INTERMED.
AB  - OBJECTIVE: We investigated whether the INTERMED, a generic instrument for
      assessing biopsychosocial case complexity and direct care, identifies organ
      transplant patients at risk of unfavourable post-transplant development by
      comparing it to the Transplant Evaluation Rating Scale (TERS), the established
      measure for pretransplant psychosocial evaluation. METHOD: One hundred nineteen
      kidney, liver, and heart transplant candidates were evaluated using the INTERMED,
      TERS, SF-36, EuroQol, Montgomery-Asberg Depression Rating Scale (MADRS), and
      Hospital Anxiety & Depression Scale (HADS). RESULTS: We found significant
      relationships between the INTERMED and the TERS scores. The INTERMED highly
      correlated with the HADS,MADRS, and mental and physical health scores of the SF
      36 Health Survey. CONCLUSIONS: The results demonstrate the validity and
      usefulness of the INTERMED instrument for pretransplant evaluation. Furthermore,
      our findings demonstrate the different qualities of INTERMED and TERS in clinical
      practice. The advantages of the psychiatric focus of the TERS and the
      biopsychosocial perspective of the INTERMED are discussed in the context of
      current literature on integrated care.

PMID- 24877579
TI  - Is the DSM-5 change in dementia labeling perilous for research?

PMID- 24877580
TI  - Re: Role of diffusion-weighted MRI in differentiation of hepatic abscesses from
      non-infected fluid collections.

PMID- 24877581
TI  - Overestimated value of (18)F-FDG PET/CT to diagnose pulmonary nodules: Analysis
      of 298 patients.
AB  - AIM: To investigate the accuracy and efficacy of combined 2-[(18)F]-fluoro-2
      deoxy-d-glucose (FDG) positron-emission tomography (PET)/computed tomography (CT)
      in the diagnosis of pulmonary nodules. MATERIAL AND METHODS: The present
      retrospective study included 298 patients with clinically suspected pulmonary
      malignancy who underwent preoperative PET/CT. The results of PET/CT were compared
      with the histopathological findings after thoracotomy or thoracoscopic surgery.
      RESULTS: Of 298 patients, pulmonary malignancy was histopathologically diagnosed
      in 248 and benign lesions in 50 patients. The sensitivity, specificity, positive
      predictive value (PPV), negative predictive value (NPV), and accuracy of PET/CT
      in detecting malignant lesions were 80.2%, 38%, 86.5%, 27.9%, and 73.1%,
      respectively. The specificity and NPV were very low, and the area under curve
      (AUC) in the receiver operating characteristic (ROC) curve analysis was 0.694.
      For 219 patients with non-small cell lung cancer (NSCLC), falsely negative
      results occurred in 43 patients. The multivariate risk-factor analysis identified
      high differentiation (p < 0.001), peripheral lung cancer (p = 0.016), non-pleural
      invasion (p = 0.001), tumour size <=3 cm (p = 0.026), adenocarcinoma (p = 0.062)
      and non-smoker (p = 0.066) as risk factors for false negatives.. CONCLUSION: The
      study suggests that the role of PET/CT in the detection of pulmonary malignancy
      has been overestimated in the past. It warrants attention that high
      differentiation, peripheral lung cancer, non-pleural invasion, tumour size <=3
      cm, adenocarcinoma, and non-smoker were independent risk factors for negative
      PET/CT findings of NSCLC..

PMID- 24877582
TI  - A new multichannel time reversal focusing method for circumferential Lamb waves
      and its applications for defect detection in thick-walled pipe with large
      diameter.
AB  - This paper proposes a new multichannel time reversal focusing (MTRF) method for
      circumferential Lamb waves which is based on modified time reversal algorithm and
      applies this method for detecting different kinds of defects in thick-walled pipe
      with large-diameter. The principle of time reversal of circumferential Lamb waves
      in pipe is presented along with the influence from multiple guided wave modes and
      propagation paths. Experimental study is carried out in a thick-walled and large
      diameter pipe with three artificial defects, namely two axial notches on its
      inner and outer surface respectively, and a corrosion-like defect on its outer
      surface. By using the proposed MTRF method, the multichannel signals focus at the
      defects, leading to the amplitude improvement of the defect scattered signal.
      Besides, another energy focus arises in the direct signal due to the partial
      compensation of dispersion and multimode of circumferential Lamb waves, alongside
      the multichannel focusing, during MTRF process. By taking the direct focus as a
      time base, accurate defect localization is implemented. Secondly, a new
      phenomenon is exhibited in this paper that defect scattered wave packet appears
      just before the right boundary of truncation window after time reversal, and to
      which two feasible explanations are given. Moreover, this phenomenon can be used
      as the theoretical basis in the determination of defect scattered waves in time
      reversal response signal. At last, in order to detect defects without prior
      knowing their exact position, a large-range truncation window is used in the
      proposed method. As a result, the experimental operation of MTRF method is
      simplified and defect detection and localization are well accomplished. 

PMID- 24877583
TI  - Total synthesis of (-)-dihydrosporothriolide utilizing an indium-mediated
      Reformatsky-Claisen rearrangement.
AB  - The asymmetric synthesis of (-)-dihydrosporothriolide (1), a biologically active
      bis-gamma-butyrolactone, is described, that proceeds through a D-proline
      catalyzed asymmetric aminooxylation, indium-mediated Reformatsky-Claisen
      rearrangement of an alpha,alpha-dibromoacetate derivative, and diastereoselective
      dihydroxylation. The route requires no protective group manipulation and allows
      the concise seven-step synthesis of 1 from n-octanal.

PMID- 24877585
TI  - Versatile triggered release of multiple molecules from cyclodextrin-modified gold
      gated mesoporous silica nanocontainers.
AB  - A versatile triggered release system by capping the cyclodextrin-modified gold
      nanoparticle onto the mesoporous silica was fabricated. The as-designed
      nanocontainers combine the merits of multiple molecules loading and sequential
      release by natural circulation manner and light initiation. 

PMID- 24877584
TI  - Total synthesis of the aristolochic acids, their major metabolites, and related
      compounds.
AB  - Plants from the Aristolochia genus have been recommended for the treatment of a
      variety of human ailments since the time of Hippocrates. However, many species
      produce the highly toxic aristolochic acids (AAs), which are both nephrotoxic and
      carcinogenic. For the purposes of extensive biological studies, a versatile
      approach to the synthesis of the AAs and their major metabolites was devised
      based primarily on a Suzuki-Miyaura coupling reaction. The key to success lies in
      the preparation of a common ring-A precursor, namely, the tetrahydropyranyl ether
      of 2-nitromethyl-3-iodo-4,5-methylendioxybenzyl alcohol (27), which was generated
      in excellent yield by oxidation of the aldoxime precursor 26. Suzuki-Miyaura
      coupling of 27 with a variety of benzaldehyde 2-boronates was accompanied by an
      aldol condensation/elimination reaction to give the desired phenanthrene
      intermediate directly. Deprotection of the benzyl alcohol followed by two
      sequential oxidation steps gave the desired phenanthrene nitrocarboxylic acids.
      This approach was used to synthesize AAs I-IV and several other related
      compounds, including AA I and AA II bearing an aminopropyloxy group at position
      6, which were required for further conversion to fluorescent biological probes.
      Further successful application of the Suzuki-Miyaura coupling reaction to the
      synthesis of the N-hydroxyaristolactams of AA I and AA II then allowed the
      synthesis of the putative, but until now elusive, N-acetoxy- and N-sulfonyloxy
      aristolactam metabolites. 

PMID- 24877586
TI  - Partially patent false lumen does not exhibit the highest growth rate.

PMID- 24877588
TI  - Is It TAVI or TAVR?

PMID- 24877587
TI  - Plasma 15-F2t-isoprostane in idiopathic pulmonary arterial hypertension.
AB  - BACKGROUND: 15-F2t-isoprostane (15-F2t-IsoP), a prostaglandin F2-like compound,
      is widely recognized as a biomarker of chronic heart failure. This study
      investigated the potential role and prognostic significance of plasma 15-F2t-IsoP
      in patients with idiopathic pulmonary arterial hypertension (IPAH). METHODS:
      Plasma 15-F2t-IsoP concentrations were determined in 80 consecutive IPAH patients
      at the time of their first right heart catheterization, and monitored for 30+/-12
      months. The expression of 15-F2t-IsoP protein in autopsy lung samples was
      determined by immunohistochemical staining. RESULTS: Plasma 15-F2t-IsoP
      concentrations were significantly increased in patients with IPAH compared with
      healthy controls (91 pg/ml vs. 30 pg/ml, respectively; P<0.001). Patients with
      baseline 15-F2t-IsoP concentrations>=97 pg/ml had a significantly lower survival
      rate than those with lower baseline concentrations (P<0.001). During follow-up,
      15-F2t-IsoP concentrations in survivors decreased, whereas concentrations in non
      surviving patients increased further (P<0.05). Elevated concentrations of 15-F2t
      IsoP were correlated with a severity of WHO functional class, lower 6-minute
      walking distance and mixed venous oxygen saturation, higher mean right atrial
      pressure and brain natriuretic peptide. Multivariate analysis revealed that the
      plasma 15-F2t-IsoP concentration was an independent factor associated with
      mortality. Histological studies showed that the expression of 15-F2t-IsoP was up
      regulated in remodeled pulmonary vessels. CONCLUSIONS: An elevated plasma 15-F2t
      IsoP concentration and a further increase during follow-up may be a risk factor
      for higher mortality in patients with IPAH.

PMID- 24877589
TI  - Combined percutaneous closure of paravalvular leaks and intraprosthetic
      regurgitation after transcatheter aortic valve implantation.

PMID- 24877591
TI  - Syncope by psychogenic hyperventilation in a patient with Chagas' disease.

PMID- 24877590
TI  - Effects of nebivolol on biomarkers in elderly patients with heart failure.
AB  - BACKGROUND: Heart failure activates neurohormones, and elevated levels of brain
      natriuretic peptide (BNP) are associated with adverse outcomes. The SENIORS trial
      showed that nebivolol, a highly selective beta-1 antagonist with vasodilating
      properties, reduced the composite outcome of all cause mortality or
      cardiovascular hospital admissions in older patients with heart failure. We
      explored the effects of nebivolol on a range of neurohormones, cytokines and
      markers of nitric oxide activity in heart failure. METHODS: In a subset of
      patients in SENIORS we measured N-terminal pro-brain natriuretic peptide (NT
      BNP), pro atrial natriuretic peptide (Pro-ANP), endothelin-1 (ET-1), peripheral
      norepinephrine (PNE), soluble Fas (sFas), soluble Fas-ligand (sFas-L), tumour
      necrosis factor-alpha (TNF-alpha), serum uric acid (SUA), symmetrical dimethyl
      arginine (SDMA), arginine, citrulline and asymmetrical dimethyl arginine (ADMA)
      at baseline (before study drug), at 6 months and 12 months in a prespecified
      substudy. RESULTS: One hundred and six patients were enrolled and 75 had a
      baseline and at least one follow-up sample. There were no significant differences
      in neurohormone cytokines or nitric oxide markers measured between the two groups
      at six or twelve months. NT-ProBNP showed a numerical increase in the nebivolol
      group compared to placebo (P=0.08) and sFas showed a numerical increase in
      patients on placebo (P=0.08). Mean baseline LVEF was 35% in both groups and at 12
      months was 43% on nebivolol group and 34% on placebo group (P=0.01). CONCLUSION:
      There were trends but no clear changes associated with nebivolol in
      neurohormones, cytokines or markers of nitric oxide activity in this study of
      elderly patients with heart failure. Further studies are needed to understand the
      mechanistic effects of beta blockers on biomarkers in heart failure.

PMID- 24877592
TI  - Smoking in China: Can or should China kick the habit?

PMID- 24877593
TI  - Effect of PEG molecular weight on stability, T2 contrast, cytotoxicity, and
      cellular uptake of superparamagnetic iron oxide nanoparticles (SPIONs).
AB  - Superparamagnetic iron oxide nanoparticles (SPIONs) are currently unavailable as
      MRI contrast agents for detecting atherosclerosis in the clinical setting because
      of either low signal enhancement or safety concerns. Therefore, a new generation
      of SPIONs with increased circulation time, enhanced image contrast, and less
      cytotoxicity is essential. In this study, monodisperse SPIONs were synthesized
      and coated with polyethylene glycol (PEG) of varying molecular weights. The
      resulting PEGylated SPIONs were characterized, and their interactions with
      vascular smooth muscle cells (VSMCs) were examined. SPIONs were tested at
      different concentrations (100 and 500 ppm Fe) for stability, T2 contrast,
      cytotoxicity, and cellular uptake to determine an optimal formulation for in vivo
      use. We found that at 100 ppm Fe, the PEG 2K SPIONs showed adequate stability and
      magnetic contrast, and exhibited the least cytotoxicity and nonspecific cellular
      uptake. An increase in cell viability was observed when the SPION-treated cells
      were washed with PBS after 1h incubation compared to 5 and 24h incubation without
      washing. Our investigation provides insight into the potential safe application
      of SPIONs in the clinic.

PMID- 24877595
TI  - Deletion mapping of the regions with AMELY from two Chinese males.
AB  - The amelogenin (AMEL) is widely used in many multiplex PCR kits for gender
      determination. However, the null of amelogenin Y (AMELY) can result in the
      incorrect genotyping of male samples as females. In this study, we report the
      deletion of AMELY in two cases with a deletion frequency of 0.019% (2/10526) in
      our laboratory. The deletion region with AMELY was mapped by using other twelve
      loci, which shows the class I deletion pattern. Further, the Y chromosome short
      tandem repeat (Y-STR) typing shows that these two cases share the same haplotype
      with other two cases from previous reports. The haplogroup of the two cases was
      predicted as O3 haplogroup with a 100% probability. Altogether, this study will
      provide evidence to further demonstrate the deletion of AMELY in Chinese
      population. 

PMID- 24877596
TI  - Detection of abused drugs in human blood by using the on-site drug-screening
      device Oratect(r) III.
AB  - A simple and precise drug screening method was developed for the detection of
      abused drugs in whole blood by using the Oratect(r) III device that is usually
      employed for the detection of drugs in saliva. Whole blood was acidified with
      phosphoric acid, following which the hemolyzed solution was filtered through the
      ultrafiltration column Vivaspin 2 Hydrosart(r). The filtrate was then tested for
      the presence of drugs using Oratect III. The detection limit of the device for
      methamphetamine, amphetamine, morphine, codeine, dihydrocodeine, diazepam,
      alprazolam, estazolam, and prazepam in whole blood was 125, 125, 50, 50, 50, 25,
      60, 15, and 75ng/mL, respectively. The concentration range detected was between
      therapeutic and toxic drug levels; therefore, the proposed method can be applied
      for detecting the presence of abused drugs in blood. Our method is a novel,
      optimized technique for use in forensic laboratories to screen whole blood for
      drugs of abuse. 

PMID- 24877594
TI  - What we know and do not know about the cannabinoid receptor 2 (CB2).
AB  - It has been well appreciated that the endocannabinoid system can regulate immune
      responses via the cannabinoid receptor 2 (CB2), which is primarily expressed by
      cells of the hematopoietic system. The endocannabinoid system is composed of
      receptors, ligands and enzymes controlling the synthesis and degradation of
      endocannabinoids. Along with endocannabinoids, both plant-derived and synthetic
      cannabinoids have been shown to bind to and signal through CB2 via G proteins
      leading to both inhibitory and stimulatory signals depending on the biological
      process. Because no cannabinoid ligand has been identified that only binds to
      CB2, the generation of mice deficient in CB2 has greatly expanded our knowledge
      of how CB2 contributes to immune cell development and function in health and
      disease. In regards to humans, genetic studies have associated CB2 with a variety
      of human diseases. Here, we review the endocannabinoid system with an emphasis on
      CB2 and its role in the immune system. 

PMID- 24877598
TI  - Biodegradation of toxic chemicals by Pleurotus eryngii in submerged fermentation
      and solid-state fermentation.
AB  - BACKGROUND/PURPOSE: The toxic chemicals bisphenol A (BPA), bisphenol F (BPF),
      nonylphenol (NP), and tetrabromobisphenol A (TBBPA) are endocrine-disrupting
      chemicals that have consequently drawn much concern regarding their effect on the
      environment. The objectives of this study were to investigate the degradation of
      BPA, BPF, NP, and TBBPA by enzymes from Pleurotus eryngii in submerged
      fermentation (SmF) and solid-state fermentation (SSF), and also to assess the
      removal of toxic chemicals in spent mushroom compost (SMC). METHODS: BPA and BPF
      were analyzed by high-performance liquid chromatography; NP and TBBPA were
      analyzed by gas chromatography. RESULTS: NP degradation was enhanced by adding
      CuSO4 (1 mM), MnSO4 (0.5 mM), gallic acid (1 mM), tartaric acid (20 mM), citric
      acid (20 mM), guaiacol (1 mM), or 2,2'-azino-bis- (3-ethylbenzothiazoline-6
      sulfonic acid; 1 mM), with the last yielding a higher NP degradation rate than
      the other additives from SmF. The optimal conditions for enzyme activity from SSF
      were a sawdust/wheat bran ratio of 1:4 and a moisture content of 5 mL/g. The
      enzyme activities were higher with sawdust/wheat bran than with sawdust/rice
      bran. The optimal conditions for the extraction of enzyme from SMC required using
      sodium acetate buffer (pH 5.0, solid/solution ratio 1:5), and extraction over 3
      hours. CONCLUSION: The removal rates of toxic chemicals by P. eryngii, in
      descending order of magnitude, were SSF > SmF > SMC. The removal rates were BPF >
      BPA > NP > TBBPA.

PMID- 24877597
TI  - The antifungal effect of silver nanoparticles on Trichosporon asahii.
AB  - BACKGROUND/PURPOSE: Silver nanoparticles are receiving increasing attention in
      biomedical applications. This study aims at evaluating the antifungal properties
      of silver nanoparticles against the pathogenic fungus Trichosporon asahii.
      METHODS: The growth of T. asahii on potato dextrose agar medium containing
      different concentrations of silver nanoparticles was examined and the antifungal
      effect was evaluated using minimum inhibitory concentration. Scanning and
      transmission electron microscopy were also used to investigate the antifungal
      effect of silver nanoparticles on T. asahii. RESULTS: Silver nanoparticles had a
      significant inhibitory effect on the growth of T. asahii. The minimum inhibitory
      concentration of silver nanoparticles against T. asahii was 0.5 MUg/mL, which was
      lower than amphotericin B, 5-flucytosine, caspofungin, terbinafine, fluconazole,
      and itraconazole and higher than voriconazole. Silver nanoparticles obviously
      damaged the cell wall, cell membrane, mitochondria, chromatin, and ribosome.
      CONCLUSION: Our results demonstrate that silver nanoparticles have good
      antifungal activity against T. asahii. Based on our electron microscopy
      observations, silver nanoparticles may inhibit the growth of T. asahii by
      permeating the fungal cell and damaging the cell wall and cellular components.

PMID- 24877599
TI  - Sleep disturbance, nocturnal agitation behaviors, and medical comorbidity in
      older adults with dementia: relationship to reported caregiver burden.
AB  - The purpose of this secondary analysis study was to determine whether care
      recipients' nighttime sleep patterns, medical comorbidity, observed nocturnal
      agitation behaviors, and caregivers' perceptions of nocturnal agitation behaviors
      in care recipients with dementia are associated with caregiver burden. Sixty care
      recipient-caregiver dyads, comprising older adults with geriatrician-diagnosed
      dementia living at home with caregivers, participated. Caregivers' perceptions of
      the frequency of care recipients' nocturnal agitation behaviors were associated
      with caregiver burden; however, objective, real-time data on the frequency of
      nocturnal agitation behaviors were not associated with burden. Care recipients'
      increased minutes of wakefulness before falling asleep and severe cognitive
      impairment with musculoskeletal/integument and neurological comorbidities were
      associated with higher caregiver burden. These results suggest that targeted
      interventions to reduce sleep onset latency, medical comorbidity, and caregivers'
      perception of frequency of nocturnal behaviors may reduce caregiver burden.

PMID- 24877600
TI  - High-efficiency "green" quantum dot solar cells.
AB  - Semiconductor quantum dots (QDs) are extremely interesting materials for the
      development of photovoltaic devices, but currently the present the drawback is
      that the most efficient devices have been prepared with toxic heavy metals of Cd
      or Pb. Solar cells based on "green" QDs--totally free of Cd or Pb--present a
      modest efficiency of 2.52%. Herein we achieve effective surface passivation of
      the ternary CuInS2 (CIS) QDs that provides high photovoltaic quality core/shell
      CIS/ZnS (CIS-Z) QDs, leading to the development of high-efficiency green QD solar
      cells that surpass the performance of those based on the toxic cadmium and lead
      chalcogenides QDs. Using wide absorption range QDs, CIS-Z-based quantum dot
      sensitized solar cell (QDSC) configuration with high QD loading and with the
      benefit of the recombination reduction with type-I core/shell structure, we boost
      the power conversion efficiency of Cd- and Pb-free QDSC to a record of 7.04%
      (with certified efficiency of 6.66%) under AM 1.5G one sun irradiation. This
      efficiency is the best performance to date for QDSCs and also demonstrates that
      it is possible to obtain comparable or even better photovoltaic performance from
      green CIS QDs to the toxic cadmium and lead chalcogenides QDs.

PMID- 24877602
TI  - Rathke's cleft cysts in twins with type 2C von Hippel-Lindau disease.
AB  - Von Hippel-Lindau disease (VHLD) is characterized by a spectrum of benign and
      malignant tumors in the CNS and visceral organs. Rathke's cleft cysts are benign,
      nonneoplastic sellar lesions that are often asymptomatic. The authors report the
      case of twin sisters with VHLD Type 2C with radiographically similar sellar
      lesions. One twin required surgery for progressive visual loss. Pathological
      examination of resected tissue demonstrated Rathke's cleft cyst. 

PMID- 24877601
TI  - Convergence of IPMK and LKB1-AMPK signaling pathways on metformin action.
AB  - Metformin is a biguanide drug that is widely prescribed for type 2 diabetes.
      Metformin suppresses hepatic gluconeogenesis and increases fatty acid oxidation.
      Although studies have suggested that metformin acts, at least in part, via
      activation of the liver kinase B1 (LKB1)/AMP-activated protein kinase (AMPK)
      pathway, the specific molecular mechanisms underlying metformin's regulation of
      glucose and lipid metabolism have not been well delineated. Recently, we have
      shown that inositol polyphosphate multikinase (IPMK) plays an important role in
      cellular energy metabolism and glucose-mediated AMPK regulation. Here we
      investigated the role of IPMK in metformin-induced AMPK activation. We observed
      that metformin-mediated activation of AMPK was impaired in the absence of IPMK.
      Overexpression of wild-type IPMK was sufficient to restore LKB1-AMPK activation
      by either metformin or AICAR in IPMK(-/-) murine embryonic fibroblast cells,
      suggesting that IPMK may act as an upstream regulator of LKB1-AMPK signaling in
      response to metformin. Moreover, this regulation was mediated by protein-protein
      interaction between IPMK and LKB1 as a dominant-negative peptide, which abrogates
      this interaction, attenuated metformin's ability to activate AMPK. Our data
      demonstrate that IPMK plays an important role in LKB1/AMPK signaling and may be
      targeted for treatment of metabolic diseases. 

PMID- 24877603
TI  - Minimizing transfusion requirements for children undergoing craniosynostosis
      repair: the CHoR protocol.
AB  - OBJECT: Children with craniosynostosis may require cranial vault remodeling to
      prevent or relieve elevated intracranial pressure and to correct the underlying
      craniofacial abnormalities. The procedure is typically associated with
      significant blood loss and high transfusion rates. The risks associated with
      transfusions are well documented and include transmission of infectious agents,
      bacterial contamination, acute hemolytic reactions, transfusion-related lung
      injury, and transfusion-related immune modulation. This study presents the
      Children's Hospital of Richmond (CHoR) protocol, which was developed to reduce
      the rate of blood transfusion in infants undergoing primary craniosynostosis
      repair. METHODS: A retrospective chart review of pediatric patients treated
      between January 2003 and Febuary 2012 was performed. The CHoR protocol was
      instituted in November 2008, with the following 3 components; 1) the use of
      preoperative erythropoietin and iron therapy, 2) the use of an intraoperative
      blood recycling device, and 3) acceptance of a lower level of hemoglobin as a
      trigger for transfusion (< 7 g/dl). Patients who underwent surgery prior to the
      protocol implementation served as controls. RESULTS: A total of 60 children were
      included in the study, 32 of whom were treated with the CHoR protocol. The
      control (C) and protocol (P) groups were comparable with respect to patient age
      (7 vs 8.4 months, p = 0.145). Recombinant erythropoietin effectively raised the
      mean preoperative hemoglobin level in the P group (12 vs 9.7 g/dl, p < 0.001).
      Although adoption of more aggressive surgical vault remodeling in 2008 resulted
      in a higher estimated blood loss (212 vs 114.5 ml, p = 0.004) and length of
      surgery (4 vs 2.8 hours, p < 0.001), transfusion was performed in significantly
      fewer cases in the P group (56% vs 96%, p < 0.001). The mean length of stay in
      the hospital was shorter for the P group (2.6 vs 3.4 days, p < 0.001).
      CONCLUSIONS: A protocol that includes preoperative administration of recombinant
      erythropoietin, intraoperative autologous blood recycling, and accepting a lower
      transfusion trigger significantly decreased transfusion utilization (p < 0.001).
      A decreased length of stay (p < 0.001) was seen, although the authors did not
      investigate whether composite transfusion complication reductions led to better
      outcomes.

PMID- 24877604
TI  - Predictors of the need for cerebrospinal fluid diversion in patients with
      myelomeningocele.
AB  - OBJECT: Many patients with myelomeningocele (MMC) develop hydrocephalus, and most
      will undergo CSF diversion. The goal of this retrospective study was to determine
      whether there was a change in the shunt rate over the 7 consecutive years of the
      study. The authors will also identify the criteria used to determine the need for
      shunt placement. METHODS: During a 7-year period, 73 patients underwent MMC
      closure at Arkansas Children's Hospital. The shunt rate for each year was
      calculated. Clinical characteristics were evaluated, including apneic and
      bradycardic spells, CSF leak, level of the MMC, head circumference, and rate of
      head growth. In addition, radiological images were reviewed, and the
      frontooccipital horn ratio (FOHR), ventricular index (VI), and thalamooccipital
      distance (TOD) were calculated. Comparisons were made between those patients who
      underwent shunt placement and those who did not. RESULTS: One patient was
      excluded due to death in the perinatal period. Of the 72 remaining patients, 54
      (75%) underwent placement of a ventriculoperitoneal shunt. This rate did not
      change significantly over time. Between the cohorts with and without a shunt
      there was no significant difference in age, sex, or race. There was no
      significant difference in apneic episodes or bradycardic episodes. There was a
      statistically significant difference in fontanelle characteristics, head
      circumference at birth, and rate of head growth. Patients who required CSF
      diversion had a mean head growth of 0.32 cm/day compared with those who did not
      receive a shunt (0.13 cm/day; p < 0.05). All radiological parameters were found
      to be statistically significant. CONCLUSIONS: In this study, several classic
      indicators of hydrocephalus in the neonate were not found to be significantly
      associated with the need for CSF diversion. Fontanelle characteristics, head
      circumference at birth, and head growth velocity were associated with the need
      for shunt placement. Imaging information including the VI, TOD, and FOHR are
      statistically significant measures to evaluate prior to placement of a
      ventriculoperitoneal shunt. The optimal patient with MMC for CSF diversion will
      have full to tense fontanelle, increasing head circumference of more than 3
      mm/day, and radiological evidence of an elevated VI, TOD, and/or FOHR.

PMID- 24877605
TI  - The role of formulation on the pharmacokinetics of antiretroviral drugs.
AB  - INTRODUCTION: A multitude of antiretroviral drug formulations are now available
      for HIV-infected adults and children. These formulations include individual and
      co-formulated drugs, many of which are also supplied in generic versions. Many
      antiretroviral drugs have a low aqueous solubility and poor bioavailability. Drug
      formulation can significantly affect bioavailability, and given the increasing
      number of new formulations and drug combinations, it is important to be aware
      that formulation can influence the pharmacokinetics of antiretroviral drugs.
      AREAS COVERED: This review provides an overview of studies assessing the
      pharmacokinetics of different antiretroviral drug formulations in adults and
      children, including fixed-dose combinations. For some antiretroviral drugs,
      differences in pharmacokinetics have been described, with largest differences in
      exposure when a liquid formulation is compared to a tablet or capsule
      formulation. Biopharmaceutical properties of antiretroviral drugs relevant to
      bioavailability are discussed. EXPERT OPINION: Antiretroviral drug formulations
      and their excipients can significantly impact drug exposure. However, this is not
      yet fully recognized. It is important to realize that children use different
      formulations than adults. Effort should be made to ensure that adequate drug
      exposures are achieved to treat HIV-infected children. In addition, manipulation
      of drug formulations may lead to differences in pharmacokinetics.

PMID- 24877607
TI  - A stereoselective ring-closing glycosylation via nonglycosylating pathway.
AB  - Two glycosyl partners were first coupled with as ester linkage, which upon
      reductive acetylation produced an alpha-acetoxy ether group. The subsequent
      activation with TfOH triggered the ring-closing process and provided the
      corresponding glycosidic bond in high beta-selectivity without relying on
      neighboring group participation. 

PMID- 24877608
TI  - Activation of inflammasomes by agents causing idiosyncratic skin reactions: a
      possible biomarker.
AB  - Chemically reactive drugs and drugs that form reactive metabolites often cause
      idiosyncratic drug reactions (IDRs); however, not all such drugs are associated
      with IDRs. Most IDRs appear to be immune mediated; therefore, the ability of a
      drug to induce an immune response may be the determinant of which drugs will
      cause IDRs. Inflammasome activation plays an important role in the initiation of
      an immune response. In this study, we studied two pairs of similar chemically
      reactive drugs, telaprevir/boceprevir and dimethyl fumarate/ethacrynic acid. In
      both pairs, the drug associated with skin reactions activated inflammasomes in
      THP-1 cells, and the drug not associated with skin reactions did not. 

PMID- 24877609
TI  - Protein binder for affinity purification of human immunoglobulin antibodies.
AB  - The importance of a downstream process for the purification of immunoglobulin
      antibodies is increasing with the growing application of monoclonal antibodies in
      many different areas. Although protein A is most commonly used for the affinity
      purification of antibodies, certain properties could be further improved: higher
      stability in alkaline solution and milder elution condition. Herein, we present
      the development of Fc-specific repebody by modular engineering approach and its
      potential as an affinity ligand for purification of human immunoglobulin
      antibodies. We previously developed the repebody scaffold composed of Leucine
      rich repeat (LRR) modules. The scaffold was shown to be highly stable over a wide
      range of pH and temperature, exhibiting a modular architecture. We first selected
      a repebody that binds the Fc fragment of human immunoglobulin G (IgG) through a
      phage display and increased its binding affinity up to 1.9 * 10(-7) M in a module
      by-module approach. The utility of the Fc-specific repebody was demonstrated by
      the performance of an immobilized repebody in affinity purification of antibodies
      from a mammalian cell-cultured medium. Bound-antibodies on an immobilized
      repebody were shown to be eluted at pH 4.0 with high purity (>94.6%) and recovery
      yield (>95.7%). The immobilized repebody allowed a repetitive purification
      process more than ten times without any loss of binding capability. The repebody
      remained almost intact even after incubation with 0.5 M NaOH for 15 days. The
      present approach could be effectively used for developing a repeat module-based
      binder for other target molecules for affinity purification. 

PMID- 24877606
TI  - Rho protein GTPases and their interactions with NFkappaB: crossroads of
      inflammation and matrix biology.
AB  - The RhoGTPases, with RhoA, Cdc42 and Rac being major members, are a group of key
      ubiquitous proteins present in all eukaryotic organisms that subserve such
      important functions as cell migration, adhesion and differentiation. The NFkappaB
      (nuclear factor kappaB) is a family of constitutive and inducible transcription
      factors that through their diverse target genes, play a major role in processes
      such as cytokine expression, stress regulation, cell division and transformation.
      Research over the past decade has uncovered new molecular links between the
      RhoGTPases and the NFkappaB pathway, with the RhoGTPases playing a positive or
      negative regulatory role on NFkappaB activation depending on the context. The
      RhoA-NFkappaB interaction has been shown to be important in cytokine-activated
      NFkappaB processes, such as those induced by TNFalpha (tumour necrosis factor
      alpha). On the other hand, Rac is important for activating the NFkappaB response
      downstream of integrin activation, such as after phagocytosis. Specific residues
      of Rac1 are important for triggering NFkappaB activation, and mutations do
      obliterate this response. Other upstream triggers of the RhoGTPase-NFkappaB
      interactions include the suppressive p120 catenin, with implications for skin
      inflammation. The networks described here are not only important areas for
      further research, but are also significant for discovery of targets for
      translational medicine. 

PMID- 24877610
TI  - Achieving highly efficient simple-emission layer fluorescence/phosphorescence
      hybrid white organic light-emitting devices via effective confinement of
      triplets.
AB  - Achieving high efficiencies in simple device configurations is a long-standing
      and meaningful target for organic light-emitting devices (OLEDs). Herein, by
      utilizing an efficient blue-violet fluorophor (CzS1) that has a high triplet
      energy of 2.62 eV, the significance of effective confinement of the green
      triplets in fluorescence/phosphorescence hybrid white devices (F/P-WOLEDs) that
      have highly simplified emission layers (EMLs) containing only RGB emitters was
      demonstrated. The non-p-i-n warm-white device exhibited excellent performance
      with a maximum forward power efficiency high up to 42.1 lm W(-1), and maintaining
      at 26.3 lm W(1-) at a practical luminance of 1000 cd m(-2). 

PMID- 24877611
TI  - Antenna-enhanced optoelectronic probing of carbon nanotubes.
AB  - We report on the first antenna-enhanced optoelectronic microscopy studies on
      nanoscale devices. By coupling the emission and excitation to a scanning optical
      antenna, we are able to locally enhance the electroluminescence and photocurrent
      along a carbon nanotube device. We show that the emission source of the
      electroluminescence can be pointlike with a spatial extension below 20 nm.
      Topographic and antenna-enhanced photocurrent measurements reveal that the
      emission takes place at the location of highest local electric field indicating
      that the mechanism behind the emission is the radiative decay of excitons created
      via impact excitation. 

PMID- 24877613
TI  - Recent advances in synthetic analogues of lantibiotics: What can we learn from
      these?
AB  - The lantibiotics are a family of antibacterial cyclic peptides distinguished by
      one or more thioether linkages between amino acid side chains, and by unique
      modes of action. Recent developments in the chemical synthesis, mutagenesis and
      mutasynthesis of these peptides are providing insights into the structural
      requirements for antibacterial activity and into the mode of action, as well as
      having the potential to produce analogues with greater stability, potency and
      bioavailability. This Review provides a survey of these recent advances. 

PMID- 24877614
TI  - [Incidence of cerebral palsy in a cohort of preterm infants with a gestational
      age of less than 28 weeks. Author's reply].

PMID- 24877615
TI  - [Comparison between 2 groups of nursing professionals on the knowledge of
      pediatric pain].
AB  - OBJECTIVE: To compare infant pain knowledge between a group of nurses who work in
      a pediatric hospital and one that works in a general hospital. MATERIAL AND
      METHODS: Descriptive study based on the use of a validated questionnaire for
      assessing the knowledge and attitudes of nurses about pediatric pain (Pediatric
      Nurses' Knowledge and Attitude Survey Regarding Pain [PNKAS]). PNKAS
      questionnaire was distributed to the nursing staff of a pediatric hospital and a
      general hospital and the results were compared. RESULTS: The average score
      obtained in the pediatric vs. the general hospital was: mean, 51.7% vs. 47.2%,
      95% confidence interval, 47.5 to 56% vs. 43.6 to 50.8% (P=.098). CONCLUSIONS:
      There were no differences between the scores in the PNKAS questionnaire between
      nurses working exclusively with children and nurses working with general
      population. Training on pediatric pain needs to be improved in nurses caring for
      sick children.

PMID- 24877616
TI  - Scattering features for lung cancer detection in fibered confocal fluorescence
      microscopy images.
AB  - OBJECTIVE: To assess the feasibility of lung cancer diagnosis using fibered
      confocal fluorescence microscopy (FCFM) imaging technique and scattering features
      for pattern recognition. METHODS: FCFM imaging technique is a new medical imaging
      technique for which interest has yet to be established for diagnosis. This paper
      addresses the problem of lung cancer detection using FCFM images and, as a first
      contribution, assesses the feasibility of computer-aided diagnosis through these
      images. Towards this aim, we have built a pattern recognition scheme which
      involves a feature extraction stage and a classification stage. The second
      contribution relies on the features used for discrimination. Indeed, we have
      employed the so-called scattering transform for extracting discriminative
      features, which are robust to small deformations in the images. We have also
      compared and combined these features with classical yet powerful features like
      local binary patterns (LBP) and their variants denoted as local quinary patterns
      (LQP). RESULTS: We show that scattering features yielded to better recognition
      performances than classical features like LBP and their LQP variants for the FCFM
      image classification problems. Another finding is that LBP-based and scattering
      based features provide complementary discriminative information and, in some
      situations, we empirically establish that performance can be improved when
      jointly using LBP, LQP and scattering features. CONCLUSIONS: In this work we
      analyze the joint capability of FCFM images and scattering features for lung
      cancer diagnosis. The proposed method achieves a good recognition rate for such a
      diagnosis problem. It also performs well when used in conjunction with other
      features for other classical medical imaging classification problems.

PMID- 24877617
TI  - Noninvasive evaluation of mental stress using by a refined rough set technique
      based on biomedical signals.
AB  - OBJECTIVE: Evaluating and treating of stress can substantially benefits to people
      with health problems. Currently, mental stress evaluated using medical
      questionnaires. However, the accuracy of this evaluation method is questionable
      because of variations caused by factors such as cultural differences and
      individual subjectivity. Measuring of biomedical signals is an effective method
      for estimating mental stress that enables this problem to be overcome. However,
      the relationship between the levels of mental stress and biomedical signals
      remain poorly understood. METHODS AND MATERIALS: A refined rough set algorithm is
      proposed to determine the relationship between mental stress and biomedical
      signals, this algorithm combines rough set theory with a hybrid Taguchi-genetic
      algorithm, called RS-HTGA. Two parameters were used for evaluating the
      performance of the proposed RS-HTGA method. A dataset obtained from a practice
      clinic comprising 362 cases (196 male, 166 female) was adopted to evaluate the
      performance of the proposed approach. RESULTS: The empirical results indicate
      that the proposed method can achieve acceptable accuracy in medical practice.
      Furthermore, the proposed method was successfully used to identify the
      relationship between mental stress levels and bio-medical signals. In addition,
      the comparison between the RS-HTGA and a support vector machine (SVM) method
      indicated that both methods yield good results. The total averages for
      sensitivity, specificity, and precision were greater than 96%, the results
      indicated that both algorithms produced highly accurate results, but a
      substantial difference in discrimination existed among people with Phase 0
      stress. The SVM algorithm shows 89% and the RS-HTGA shows 96%. Therefore, the RS
      HTGA is superior to the SVM algorithm. The kappa test results for both algorithms
      were greater than 0.936, indicating high accuracy and consistency. The area under
      receiver operating characteristic curve for both the RS-HTGA and a SVM method
      were greater than 0.77, indicating a good discrimination capability. CONCLUSIONS:
      In this study, crucial attributes in stress evaluation were successfully
      recognized using biomedical signals, thereby enabling the conservation of medical
      resources and elucidating the mapping relationship between levels of mental
      stress and candidate attributes. In addition, we developed a prototype system for
      mental stress evaluation that can be used to provide benefits in medical
      practice.

PMID- 24877618
TI  - Advanced portable remote monitoring system for the regulation of treadmill
      running exercises.
AB  - OBJECTIVE: This study aims to develop an advanced portable remote monitoring
      system to supervise high intensity treadmill exercises. MATERIALS AND METHODS:
      The supervisory level of the developed hierarchical system is implemented on a
      portable monitoring device (iPhone/iPad) as a client application, while the real
      time control of treadmill exercises is accomplished by using an on-line adaptive
      neural network control scheme in a local computer system. During training or
      rehabilitation exercises, the intensity (measured by heart rate) is regulated by
      simultaneously manipulating both treadmill speed and gradient. In order to
      achieve adaptive tracking performance, a neural network controller has been
      designed and implemented. RESULTS: Six real-time experiments have been conducted
      to test the performance of the developed monitoring system. Experimental results
      obtained in real-time with heart-rate set-point varying from 145 bpm to 180 bmp,
      demonstrate that the proposed system can quickly and accurately regulate exercise
      intensity of treadmill running exercises with desired performance (no overshoot,
      settling time Ts <= 100 s). Subjects aged from 29 to 38 years old participated in
      different set-point experiments to confirm the system's adaptability to inter-
      and intra-model uncertainty. The desired system performance under external
      disturbances has also been confirmed in a final real-time experiment
      demonstrating a user carrying the 10 kg bag then removing it during the exercise.
      CONCLUSION: In contrast with conventional control approaches, the proposed
      adaptive controller achieves better heart rate tracking performance under inter-
      and intra-model uncertainty and external disturbances. The developed system can
      automatically adapt to various individual exercisers and a range of exercise
      intensity.

PMID- 24877619
TI  - Elucidation of the Na(2/3)FePO4 and Li(2/3)FePO4 intermediate superstructure
      revealing a pseudouniform ordering in 2D.
AB  - Based on TEM, synchrotron X-ray diffraction, DFT calculations, and Mossbauer
      spectroscopy, a unified understanding of the Na and Li intercalation process in
      FePO4 is proposed. The key to this lies in solving the highly sought-after
      intermediate A(2/3)FePO4 (A = Na, Li) superstructures that are characterized by
      alkali ions as well as Fe(II)/Fe(III) charge orderings in a monoclinic three-fold
      supercell. Formation energies and electrochemical potential calculations confirm
      that Na(2/3)FePO4 and Li(2/3)FePO4 are stable and metastable, respectively, and
      that they yield insertion potentials in fair agreement with experimental values.
      The 2/3 Na(Li) and 1/3 vacancy sublattice of the intermediate phases forms a
      dense (101)(Pnma) plane in which the atom/vacancy ordering is very similar to
      that predicted for the most uniform distribution of 1/3 of vacancies in a 2D
      square lattice. Structural analysis strongly suggests that the key role of this
      dense plane is to constrain the intercalation in the diffusion channels to
      operate by cooperative filling of (bc)(Pnma). From a practical point of view,
      this generalized mechanism highlights the fact that an interesting strategy for
      obtaining high-rate FePO4 materials would consist in designing grains with an
      enhanced (101) surface area, thereby offering potential for substantial
      improvements with respect to the performance of rechargeable Li and Na batteries.

PMID- 24877620
TI  - Erratum.

PMID- 24877621
TI  - Differences in plantarflexor function during a stretch-shortening cycle task due
      to limb preference.
AB  - Most healthy humans move symmetrically at gross limb level but large kinetic and
      kinematic asymmetries have been observed at joint level during locomotion. The
      aim of this study was to assess muscle function asymmetries in healthy, active
      adults using an adapted force sledge apparatus which isolates the plantarflexors
      during a stretch-shortening cycle (SSC) task. Peak force, rate of force
      development and SSC function of preferred and non-preferred limbs were assessed
      in 21 healthy, active individuals using the adapted sledge and three-dimensional
      motion analysis. Between-limb differences and relationships were determined using
      paired t-tests/Wilcoxon Signed-rank test, Cohen's dz, absolute symmetry index and
      Pearson's r/Spearman's rho. Significant differences with moderate effect size
      (ES) were observed in peak force (ES: 0.66), rate of peak force development (ES:
      0.78), rate of force development in the first 50 ms (ES: 0.76), flight time (ES:
      0.64) and SSC function (0.68), with no difference in contact time or duration of
      eccentric loading. A small ES (0.56) was observed in rate of force development in
      the first 30 ms. The upper range of asymmetry observed (up to 44.6%) was larger
      than previously reported for healthy individuals, indicating compensations occur
      at proximal joints during locomotion to ensure symmetrical movement. 

PMID- 24877622
TI  - The medial amygdala-medullary PrRP-synthesizing neuron pathway mediates
      neuroendocrine responses to contextual conditioned fear in male rodents.
AB  - Fear responses play evolutionarily beneficial roles, although excessive fear
      memory can induce inappropriate fear expression observed in posttraumatic stress
      disorder, panic disorder, and phobia. To understand the neural machineries that
      underlie these disorders, it is important to clarify the neural pathways of fear
      responses. Contextual conditioned fear induces freezing behavior and
      neuroendocrine responses. Considerable evidence indicates that the central
      amygdala plays an essential role in expression of freezing behavior after
      contextual conditioned fear. On the other hand, mechanisms of neuroendocrine
      responses remain to be clarified. The medial amygdala (MeA), which is activated
      after contextual conditioned fear, was lesioned bilaterally by infusion of N
      methyl-d-aspartate after training of fear conditioning. Plasma oxytocin, ACTH,
      and prolactin concentrations were significantly increased after contextual
      conditioned fear in sham-lesioned rats. In MeA-lesioned rats, these
      neuroendocrine responses but not freezing behavior were significantly impaired
      compared with those in sham-lesioned rats. In contrast, the magnitudes of
      neuroendocrine responses after exposure to novel environmental stimuli were not
      significantly different in MeA-lesioned rats and sham-lesioned rats. Contextual
      conditioned fear activated prolactin-releasing peptide (PrRP)-synthesizing
      neurons in the medulla oblongata. In MeA-lesioned rats, the percentage of PrRP
      synthesizing neurons activated after contextual conditioned fear was
      significantly decreased. Furthermore, neuroendocrine responses after contextual
      conditioned fear disappeared in PrRP-deficient mice. Our findings suggest that
      the MeA-medullary PrRP-synthesizing neuron pathway plays an important role in
      neuroendocrine responses to contextual conditioned fear. 

PMID- 24877623
TI  - Estradiol modulates translocator protein (TSPO) and steroid acute regulatory
      protein (StAR) via protein kinase A (PKA) signaling in hypothalamic astrocytes.
AB  - The ability of the central nervous system to synthesize steroid hormones has wide
      ranging implications for physiology and pathology. Among the proposed roles of
      neurosteroids is the regulation of the LH surge. This involvement in the estrogen
      positive feedback demonstrates the integration of peripheral steroids with
      neurosteroids. Within the female hypothalamus, estradiol from developing
      follicles stimulates progesterone synthesis in astrocytes, which activate neural
      circuits regulating gonadotropin (GnRH) neurons. Estradiol acts at membrane
      estrogen receptor-alpha to activate cellular signaling that results in the
      release of inositol trisphosphate-sensitive calcium stores that are sufficient to
      induce neuroprogesterone synthesis. The purpose of the present studies was to
      characterize the estradiol-induced signaling leading to activation of steroid
      acute regulatory protein (StAR) and transporter protein (TSPO), which mediate the
      rate-limiting step in steroidogenesis, ie, the transport of cholesterol into the
      mitochondrion. Treatment of primary cultures of adult female rat hypothalamic
      astrocytes with estradiol induced a cascade of phosphorylation that resulted in
      the activation of a calcium-dependent adenylyl cyclase, AC1, elevation of cAMP,
      and activation of both StAR and TSPO. Blocking protein kinase A activation with H
      89 abrogated the estradiol-induced neuroprogesterone synthesis. Thus, together
      with previous results, these experiments completed the characterization of how
      estradiol action at the membrane leads to the augmentation of neuroprogesterone
      synthesis through increasing cAMP, activation of protein kinase A, and the
      phosphorylation of TSPO and StAR in hypothalamic astrocytes. 

PMID- 24877625
TI  - Loss of follicle-stimulating hormone receptor function causes masculinization and
      suppression of ovarian development in genetically female medaka.
AB  - FSH, a glycoprotein hormone, is circulated from the pituitary and functions by
      binding to a specific FSH receptor (FSHR). FSHR is a G protein-coupled, seven
      transmembrane receptor linked to the adenylyl cyclase or other pathways and is
      expressed in gonadal somatic cells. In some nonmammalian species, fshr expression
      is much higher in the ovary than in the testis during gonadal sex
      differentiation, suggesting that FSHR is involved in ovarian development in
      nonmammalian vertebrates. However, little is known of FSHR knockout phenotypes in
      these species. Here we screened for fshr mutations by a medaka (Oryzias latipes)
      target-induced local lesion in the genomes and identified one nonsense mutation
      located in the BXXBB motif, which is involved in G protein activation. Next, we
      used an in vitro reporter gene assay to demonstrate that this mutation prevents
      FSHR function. We then analyzed the phenotypes of fshr mutant medaka. The fshr
      mutant male medaka displayed normal testes and were fertile, whereas the mutant
      female fish displayed small ovaries and were infertile because vitellogenesis was
      inhibited. The mutant females also have suppressed expression of ovary-type
      aromatase (cyp19a1a), a steroidogenic enzyme responsible for the conversion of
      androgens to estrogens, resulting in decreased 17beta-estradiol levels. Moreover,
      loss of FSHR function caused female-to-male sex reversal in some cases. In
      addition, the transgenic overexpression of fshr in fshr mutants rescued FSHR
      function. These findings strongly suggest that in the medaka, FSH regulates the
      ovarian development and the maintenance mainly by the elevation of estrogen
      levels. We present the first FSHR knockout phenotype in a nonmammalian species. 

PMID- 24877624
TI  - Implantation failure in female Kiss1-/- mice is independent of their hypogonadic
      state and can be partially rescued by leukemia inhibitory factor.
AB  - The hypothalamic kisspeptin signaling system is a major positive regulator of the
      reproductive neuroendocrine axis, and loss of Kiss1 in the mouse results in
      infertility, a condition generally attributed to its hypogonadotropic
      hypogonadism. We demonstrate that in Kiss1(-/-) female mice, acute replacement of
      gonadotropins and estradiol restores ovulation, mating, and fertilization;
      however, these mice are still unable to achieve pregnancy because embryos fail to
      implant. Progesterone treatment did not overcome this defect. Kiss1(+/-) embryos
      transferred to a wild-type female mouse can successfully implant, demonstrating
      the defect is due to maternal factors. Kisspeptin and its receptor are expressed
      in the mouse uterus, and we suggest that it is the absence of uterine kisspeptin
      signaling that underlies the implantation failure. This absence, however, does
      not prevent the closure of the uterine implantation chamber, proper alignment of
      the embryo, and the ability of the uterus to undergo decidualization. Instead,
      the loss of Kiss1 expression specifically disrupts embryo attachment to the
      uterus. We observed that on the day of implantation, leukemia inhibitory factor
      (Lif), a cytokine that is absolutely required for implantation in mice, is weakly
      expressed in Kiss1(-/-) uterine glands and that the administration of exogenous
      Lif to hormone-primed Kiss1(-/-) female mice is sufficient to partially rescue
      implantation. Taken together, our study reveals that uterine kisspeptin signaling
      regulates glandular Lif levels, thereby identifying a novel and critical role for
      kisspeptin in regulating embryo implantation in the mouse. This study provides
      compelling reasons to explore this role in other species, particularly livestock
      and humans. 

PMID- 24877626
TI  - 5TNF-alpha and IL-1beta neutralization ameliorates angiotensin II-induced cardiac
      damage in male mice.
AB  - Inflammation is a key event in hypertensive organ damage, and TNF-alpha and IL
      1beta are elevated in hypertension. In this study, we evaluated the effects of
      TNF-alpha and IL-1beta elevation on hypertensive cardiac damage by treatment with
      a bifunctional inflammatory inhibitor, TNF receptor 2-fragment crystalization-IL
      1 receptor antagonist (TFI), which can neutralize these 2 cytokines
      simultaneously. A mouse hypertension model of angiotensin II (Ang II) infusion
      (1500 ng/kg.min for 7 d) was induced in wild-type mice. TNF-alpha and IL-1beta
      were inhibited by TFI administration (5 mg/kg, every other day), the effects of
      inhibition on cardiac damage were examined, and its mechanism on inflammatory
      infiltration was further studied in vivo and in vitro. Ang II infusion induced
      cardiac injury, including increased macrophage infiltration, expression of
      inflammatory cytokines (IL-12, IL-6, etc), and cardiac fibrosis, such as elevated
      alpha-smooth muscle actin, collagen I, and TGF-beta expression. Importantly, the
      Ang II-induced cardiac injury was suppressed by TFI treatment. Moreover, TFI
      reduced the expression of adhesion molecules (intercellular adhesion molecule-1
      and vascular cell adhesion molecule-1) and monocyte chemotactic protein-1
      expression in Ang II-treated hearts. Additionally, blockade of TNF-alpha and IL
      1beta by TFI reduced monocyte adherence to endothelia cell and macrophage
      migration. This study demonstrates that blocking TNF-alpha and IL-1beta by TFI
      prevents cardiac damage in response to Ang II, and targeting these 2 cytokines
      simultaneously might be a novel tool to treat hypertensive heart injury. 

PMID- 24877628
TI  - Lgr4 gene regulates corpus luteum maturation through modulation of the WNT
      mediated EGFR-ERK signaling pathway.
AB  - Luteal-phase insufficiency is one of the major causes of female infertility, but
      the molecular mechanisms are still largely unknown. Here we found that disruption
      of Lgr4/Gpr48, the newly identified receptor for R-spondins, greatly reduced
      female fertility in mice. The expression of Lgr4 was induced specifically in
      granulosa-lutein cells during luteinization. In Lgr4-deficient female mice, the
      estrous cycle was prolonged and serum progesterone levels were dramatically
      downregulated. In Lgr4(-/-) corpora lutea, the expression of key enzymes for
      steroidogenesis as well as common luteal marker genes was significantly
      decreased. Additionally, the activity of epidermal growth factor receptor (EGFR)
      ERK signaling was attenuated in Lgr4(-/-) granulosa-lutein cells. We found that
      the maturation of Lgr4(-/-) cells was impaired in cultured primary granulosa
      cells, but the defect was partially rescued by reactivation of EGFR signaling by
      heparin-binding EGF-like growth factor treatment. We found that the expression of
      wingless-type MMTV integration site family (WNT)/catenin (cadherin associated
      protein), beta 1 (CTNNB1) downstream targets, including matrix metalloproteinase
      9, which is a critical matrix metalloproteinase for activation of EGF-like
      factors, was significantly downregulated in Lgr4(-/-) ovaries. Matrix
      metalloproteinase 9 inhibitor treatment attenuated human chorionic gonadotropin-
      but not heparin-binding EGF-like growth factor-induced ERK activation and
      luteinization in primary granulosa cells. Together, we report that Lgr4 modulates
      WNT-mediated EGFR-ERK signaling to facilitate corpus luteum maturation and
      ovarian steroidogenesis to maintain female reproduction. 

PMID- 24877627
TI  - Endogenous NO upon estradiol-17beta stimulation and NO donor differentially
      regulate mitochondrial S-nitrosylation in endothelial cells.
AB  - Adduction of a nitric oxide (NO) moiety (NO(*)) to cysteines termed as S
      nitrosylation (SNO) has emerged as a crucial mechanism for NO signaling crucial
      for mediating the vascular effects of estrogens. Mitochondrion is a known
      vascular risk factor; however, the effects of estrogens on mitochondrial SNO are
      incompletely understood. In this study we determined the effects of estradiol
      17beta (E2beta) on mitochondrial protein SNO in primary human umbilical vein
      endothelial cells and compared the mitochondrial nitroso-proteomes in E2beta- and
      a NO donor S-nitrosoglutathione (GSNO)-treated cells using a proteomics approach.
      Treatment with 10 nM E2beta and 1 mM GSNO for 30 minutes significantly increased
      the levels of mitochondrial SNO-proteins. Subcellular localization of SNO
      proteins showed mitochondria as the major cellular organelle for protein SNO in
      response to E2beta and GSNO. E2beta stimulated mitochondrial endothelial nitric
      oxide synthase (eNOS) phosphorylation and mitochondrial protein SNO that was
      enhanced by overexpression of mitochondrion or Golgi, but not membrane targeting
      eNOS constructs. We identified 11, 32, and 54 SNO-proteins in the mitochondria
      from the untreated, E2beta-, and GSNO-treated human umbilical vein endothelial
      cells, respectively. Comparisons of the nitroso-proteomes revealed that common
      and different mitochondrial SNO-proteins were affected by endogenous NO on E2beta
      stimulation and exogenous NO from donor. These SNO-proteins were associated with
      various mitochondrial functions, including energy and redox regulation,
      transport, iron homeostasis, translation, mitochondrial morphology, and
      apoptosis, etc. Collectively, we conclude that estrogens rapidly stimulate
      protein SNO in endothelial mitochondria via mitochondrial eNOS, providing a
      mechanism for mediating the vascular effects of estrogens. 

PMID- 24877629
TI  - SIRT3 positively regulates the expression of folliculogenesis- and luteinization
      related genes and progesterone secretion by manipulating oxidative stress in
      human luteinized granulosa cells.
AB  - SIRT3 is a member of the sirtuin family and has recently emerged as a vital
      molecule in controlling the generation of reactive oxygen species (ROS) in
      oocytes. Appropriate levels of ROS play pivotal roles in human reproductive
      medicine. The aim of the present study was to investigate SIRT3 expression and
      analyze the SIRT3-mediated oxidative response in human luteinized granulosa cells
      (GCs). Human ovarian tissues were subjected to immunohistochemical analysis to
      localize SIRT3 expression. Hydrogen peroxide and human chorionic gonadotropin
      were used to analyze the relationship between ROS and SIRT3 by quantitative RT
      PCR and Western blotting. Intracellular levels of ROS were investigated by
      fluorescence after small interfering RNA-mediated knockdown of SIRT3 in human
      GCs. To uncover the role of SIRT3 in folliculogenesis and luteinization, mRNA
      levels of related genes and the progesterone concentration were analyzed by
      quantitative RT-PCR and immunoassays, respectively. We detected the expression of
      SIRT3 in the GCs of the human ovary. The mRNA levels of SIRT3, catalase, and
      superoxide dismutase 1 were up-regulated by hydrogen peroxide in both COV434
      cells and human GCs and down-regulated by human chorionic gonadotropin. Knockdown
      of SIRT3 markedly elevated ROS generation in human GCs. In addition, SIRT3
      depletion resulted in decreased mRNA expression of aromatase, 17beta
      hydroxysteroid dehydrogenase 1, steroidogenic acute regulatory protein,
      cholesterol side-chain cleavage enzyme, and 3beta-hydroxysteroid dehydrogenase in
      GCs and thus resulted in decreased progesterone secretion. These results have the
      important clinical implication that SIRT3 might play a positive role in the
      folliculogenesis and luteinization processes in GCs, possibly by sensing and
      regulating the generation of ROS. Activation of SIRT3 function might help to
      sustain human reproduction by maintaining GCs as well as oocytes. 

PMID- 24877630
TI  - Parathyroid hormone receptor signaling induces bone resorption in the adult
      skeleton by directly regulating the RANKL gene in osteocytes.
AB  - PTH upregulates the expression of the receptor activator of nuclear factor kappaB
      ligand (Rankl) in cells of the osteoblastic lineage, but the precise
      differentiation stage of the PTH target cell responsible for RANKL-mediated
      stimulation of bone resorption remains undefined. We report that constitutive
      activation of PTH receptor signaling only in osteocytes in transgenic mice (DMP1
      caPTHR1) was sufficient to increase Rankl expression and bone resorption.
      Resorption in DMP1-caPTHR1 mice crossed with mice lacking the distal control
      region regulated by PTH in the Rankl gene (DCR(-/-)) was similar to DMP1-caPTHR1
      mice at 1 month of age, but progressively declined to reach values
      undistinguishable from wild-type (WT) mice at 5 months of age. Moreover, DMP1
      caPTHR1 mice exhibited low tissue material density and increased serum alkaline
      phosphatase activity at 5 month of age, and these indices of high remodeling were
      partially and totally corrected in compound DMP1-caPTHR1;DCR(-/-) male mice, and
      less affected in female mice. Rankl expression in bones from DMP1-caPTHR1 mice
      was elevated at both 1 and 5 months of age, whereas it was high, similar to DMP1
      caPTHR1 mice at 1 month, but low, similar to WT levels at 5 months in compound
      mice. Moreover, PTH increased Rankl and decreased Sost and Opg expression in ex
      vivo bone organ cultures established from WT mice, but only regulated Sost and
      Opg expression in cultures from DCR(-/-) mice. PTH also increased RANKL
      expression in osteocyte-containing primary cultures of calvarial cells, in
      isolated murine osteocytes, and in WT but not in DCR(-/-) osteocyte-enriched
      bones. Thus, PTH upregulates Rankl expression in osteocytes in vitro, ex vivo and
      in vivo, and resorption induced by PTH receptor signaling in the adult skeleton
      requires direct regulation of the Rankl gene in osteocytes. 

PMID- 24877631
TI  - Loss of Ntrk2/Kiss1r signaling in oocytes causes premature ovarian failure.
AB  - Neurotrophins (NTs), once believed to be neural-specific trophic factors, are now
      known to also provide developmental cues to non-neural cells. In the ovary, NTs
      contribute to both the formation and development of follicles. Here we show that
      oocyte-specific deletion of the Ntrk2 gene that encodes the NTRK2 receptor
      (NTRK2) for neurotrophin-4/5 and brain-derived neurotrophic factor (BDNF) results
      in post-pubertal oocyte death, loss of follicular organization, and early
      adulthood infertility. Oocytes lacking NTRK2 do not respond to gonadotropins with
      activation of phosphatidylinositol 3-kinase (PI3K)-AKT-mediated signaling. Before
      puberty, oocytes only express a truncated NTRK2 form (NTRK2.T1), but at puberty
      full-length (NTRK2.FL) receptors are rapidly induced by the preovulatory
      gonadotropin surge. A cell line expressing both NTRK2.T1 and the kisspeptin
      receptor (KISS1R) responds to BDNF stimulation with activation of Ntrk2
      expression only if kisspeptin is present. This suggests that BDNF and kisspeptin
      that are produced by granulosa cells (GCs) of periovulatory follicles act in
      concert to mediate the effect of gonadotropins on Ntrk2 expression in oocytes. In
      keeping with this finding, the oocytes of NTRK2-intact mice fail to respond to
      gonadotropins with increased Ntrk2 expression in the absence of KISS1R. Our
      results demonstrate that the preovulatory gonadotropin surge promotes oocyte
      survival at the onset of reproductive cyclicity by inducing oocyte expression of
      NTRK2.FL receptors that set in motion an AKT-mediated survival pathway. They also
      suggest that gonadotropins activate NTRK2.FL expression via a dual communication
      pathway involving BDNF and kisspeptin produced in GCs and their respective
      receptors NTRK2.T1 and KISS1R expressed in oocytes. 

PMID- 24877633
TI  - Characterization of reproductive, metabolic, and endocrine features of polycystic
      ovary syndrome in female hyperandrogenic mouse models.
AB  - Polycystic ovary syndrome (PCOS) affects 5-10% of women of reproductive age,
      causing a range of reproductive, metabolic and endocrine defects including
      anovulation, infertility, hyperandrogenism, obesity, hyperinsulinism, and an
      increased risk of type 2 diabetes and cardiovascular disease. Hyperandrogenism is
      the most consistent feature of PCOS, but its etiology remains unknown, and
      ethical and logistic constraints limit definitive experimentation in humans to
      determine mechanisms involved. In this study, we provide the first comprehensive
      characterization of reproductive, endocrine, and metabolic PCOS traits in 4
      distinct murine models of hyperandrogenism, comprising prenatal
      dihydrotestosterone (DHT, potent nonaromatizable androgen) treatment during days
      16-18 of gestation, or long-term treatment (90 days from 21 days of age) with
      DHT, dehydroepiandrosterone (DHEA), or letrozole (aromatase inhibitor). Prenatal
      DHT-treated mature mice exhibited irregular estrous cycles, oligo-ovulation,
      reduced preantral follicle health, hepatic steatosis, and adipocyte hypertrophy,
      but lacked overall changes in body-fat composition. Long-term DHT treatment
      induced polycystic ovaries displaying unhealthy antral follicles (degenerate
      oocyte and/or > 10% pyknotic granulosa cells), as well as anovulation and
      acyclicity in mature (16-week-old) females. Long-term DHT also increased body and
      fat pad weights and induced adipocyte hypertrophy and hypercholesterolemia. Long
      term letrozole-treated mice exhibited absent or irregular cycles, oligo
      ovulation, polycystic ovaries containing hemorrhagic cysts atypical of PCOS, and
      displayed no metabolic features of PCOS. Long-term dehydroepiandrosterone
      treatment produced no PCOS features in mature mice. Our findings reveal that long
      term DHT treatment replicated a breadth of ovarian, endocrine, and metabolic
      features of human PCOS and provides the best mouse model for experimental studies
      of PCOS pathogenesis. 

PMID- 24877634
TI  - Circadian dynamics of the cone-rod homeobox (CRX) transcription factor in the rat
      pineal gland and its role in regulation of arylalkylamine N-acetyltransferase
      (AANAT).
AB  - The cone-rod homeobox (Crx) gene encodes a transcription factor in the retina and
      pineal gland. Crx deficiency influences the pineal transcriptome, including a
      reduced expression of arylalkylamine N-acetyltransferase (Aanat), a key enzyme in
      nocturnal pineal melatonin production. However, previous functional studies on
      pineal Crx have been performed in melatonin-deficient mice. In this study, we
      have investigated the role of Crx in the melatonin-proficient rat pineal gland.
      The current study shows that pineal Crx transcript levels exhibit a circadian
      rhythm with a peak in the middle of the night, which is transferred into daily
      changes in CRX protein. The study further shows that the sympathetic innervation
      of the pineal gland controls the Crx rhythm. By use of adenovirus-mediated short
      hairpin RNA gene knockdown targeting Crx mRNA in primary rat pinealocyte cell
      culture, we here show that intact levels of Crx mRNA are required to obtain high
      levels of Aanat expression, whereas overexpression of Crx induces Aanat
      transcription in vitro. This regulatory function of Crx is further supported by
      circadian analysis of Aanat in the pineal gland of the Crx-knockout mouse. Our
      data indicate that the rhythmic nature of pineal CRX protein may directly
      modulate the daily profile of Aanat expression by inducing nighttime expression
      of this enzyme, thus facilitating nocturnal melatonin synthesis in addition to
      its role in ensuring a correct tissue distribution of Aanat expression. 

PMID- 24877632
TI  - Hindbrain oxytocin receptors contribute to the effects of circulating oxytocin on
      food intake in male rats.
AB  - Oxytocin (OT)-elicited hypophagia has been linked to neural activity in the
      nucleus of the solitary tract (NTS). Because plasma OT levels increase after a
      meal, we hypothesized that circulating OT acts at both peripheral and hindbrain
      OT receptors (OTRs) to limit food intake. To initially determine whether
      circulating OT inhibits food intake by acting at hindbrain OTRs, we pretreated
      rats with an OTR antagonist administered into the fourth ventricle (4V) followed
      by either central or systemic OT administration. Administration of the OTR
      antagonist into the 4V blocked anorexia induced by either 4V or i.p. injection of
      OT. However, blockade of peripheral OTRs also weakened the anorectic response to
      ip OT. Our data suggest a predominant role for hindbrain OTRs in the hypophagic
      response to peripheral OT administration. To elucidate central mechanisms of OT
      hypophagia, we tested whether OT activates NTS catecholaminergic neurons. OT (ip)
      increased the number of NTS cells expressing c-Fos, of which 10%-15% were
      catecholaminergic. Furthermore, electrophysiological studies in mice revealed
      that OT stimulated 47% (8 of 17) of NTS catecholamine neurons through a
      presynaptic mechanism. However, OT-elicited hypophagia did not appear to require
      activation of alpha1-adrenoceptors, and blockade of glucagon-like peptide-1
      receptors similarly did not attenuate anorexia induced by OT. These findings
      demonstrate that OT elicits satiety through both central and peripheral OTRs and
      that although catecholamine neurons are a downstream target of OT signaling in
      the NTS, the hypophagic effect is mediated independently of alpha1-adrenoceptor
      signaling.

PMID- 24877635
TI  - Effect of adiposity, season, diet and calcium or vitamin D supplementation on the
      vitamin D status of healthy urban African and Asian-Indian adults.
AB  - Vitamin D deficiency has been implicated in the aetiology of infectious diseases
      and metabolic syndrome. These diseases are prevalent in the African and Asian
      Indian populations of South Africa; however, there is limited data on 25
      hydroxyvitamin D (25(OH)D) concentrations in these populations. The aim of the
      present study was to assess the vitamin D status and its predictors in healthy
      adults in Johannesburg. We assessed the vitamin D status of 730 adult African and
      Asian-Indian subjects residing in Johannesburg. The contributions of sun
      exposure, season, dietary intake of Ca and vitamin D, total body fat and body fat
      distribution to 25(OH)D concentrations were assessed. The concentrations of
      25(OH)D were measured by HPLC. The contribution of 25(OH)D3 to total 25(OH)D
      concentrations was assessed. The mean age of the subjects was 42.6 (SD 13.1)
      years (range: 18-65). Concentrations of 25(OH)D < 30 nmol/l were found in 28.6 %
      of the Asian-Indian subjects in comparison with 5.1 % of the African subjects (P<
      0.0001). Parathyroid hormone (PTH) concentrations were negatively associated with
      25(OH)D concentrations, while season and sun exposure were positive predictors
      explaining 16 % of the variance in 25(OH)D concentrations (P< 0.0001) in the
      African subjects. In the Asian-Indian subjects, PTH concentrations were
      negatively associated with 25(OH)D concentrations, while male sex, season and Ca
      supplementation were positive predictors and explained 17 % of the variance in
      25(OH)D concentrations (P< 0.0001). In the multivariate regression analysis,
      neither total body fat nor body fat distribution was predictive of 25(OH)D
      concentrations in either group. In conclusion, factors such as sun exposure,
      dietary supplement use and ethnicity are important determinants of plasma 25(OH)D
      concentrations.

PMID- 24877636
TI  - Vitelliform focal choroidal excavation.
AB  - Focal choroidal excavations (FCE) are characterized by foveal or perifoveal
      choroid excavations seen on optical coherence tomography (OCT). The authors
      report a case of FCE associated with a vitelliform lesion within the excavation.
      A case of FCE associated with a small vitelliform lesion has been described
      previously, but the larger extent of the vitelliform lesion observed in the
      current case has not been previously reported. This may represent a novel
      category of FCE, vitelliform focal choroidal excavation, in which deposition of
      vitelliform material is associated with its development.

PMID- 24877637
TI  - Assessing diurnal variation in choroidal thickness.

PMID- 24877638
TI  - Hispidin derived from Phellinus linteus affords protection against acrylamide
      induced oxidative stress in Caco-2 cells.
AB  - Acrylamide (AA), a well-known toxicant, has attracted numerous attentions for its
      presumably carcinogenesis, neurotoxicity and cytotoxicity. Oxidative stress was
      considered to be associated with acrylamide cytotoxicity, but the link between
      oxidative stress and acrylamide cytotoxicity is still unclear. In the present
      study, hispidin produced from the edible fungus Phellinus linteus displayed
      dramatically antioxidant activities against DPPH radicals, ABTS radicals, ferric
      reducing and hydroxyl radicals, as well as superoxide anion radicals. Moreover,
      the cytoprotective effect of hispidin against AA-induced oxidative stress was
      verified upon Caco-2 cells according to evaluate the cell viability,
      intracellular ROS, mitochondrial membrane potential (MMP) and glutathione (GSH)
      in the presence or absence of AA (5 mM) in a dose-dependent manner. Collectively,
      our results demonstrated for the first time that hispidin was able to inhibit AA
      induced oxidative stress, which might have implication for the dietary preventive
      application.

PMID- 24877639
TI  - Ellagic acid, an NF-kappaB inhibitor, ameliorates renal function in experimental
      diabetic nephropathy.
AB  - Diabetic nephropathy (DN) is a serious complication confronted by diabetic
      patients. Available data indicate that the development of DN is linked to
      inflammation. In this context, nuclear factor-kappa B (NF-kappaB) has received
      much attention. Ellagic acid (2,3,7,8-tetrahydroxy-chromeno[5,4,3-cde]chromene
      5,10-dione), found abundantly in plant extracts and fruits, possesses numerous
      medicinal properties. We investigated the nephroprotective effects of oral
      treatment of ellagic acid in high fat diet/low dose streptozotocin (HFD/STZ)
      induced type 2 diabetic Wistar albino rats. Ellagic acid treatment for 16weeks
      post induction of diabetes significantly attenuated renal dysfunction and
      oxidative stress. Ellagic acid significantly inhibited the renal NF-kB
      activation. Moreover, ellagic acid significantly lowered renal pathology and
      suppressed transforming growth factor-beta (TGF-beta) and fibronectin expressions
      in renal tissues. Ellagic acid also significantly reduced the serum levels of pro
      inflammatory cytokines, interleukin-1beta (IL-1beta), IL-6 and tumor necrosis
      factor-alpha (TNF-alpha). In cultured rat NRK 52E proximal tubular epithelial
      cells, ellagic acid treatment inhibited high glucose-induced activation of NF
      kappaB and pro-inflammatory cytokine synthesis. These results suggest that
      ellagic acid exhibited renal protective effect in diabetic rats partly through
      antihyperglycemia which was accompanied by attenuation of inflammatory processes
      via inhibition of NF-kappaB pathway. 

PMID- 24877640
TI  - Sophoricoside fails the embryo implantation by compromising the uterine
      endometrial receptivity at implantation "window" of pregnant mice.
AB  - Sophoricoside (SOPH) is an isoflavone glycoside isolated from the fruits of
      Sophora japonica. Since its first isolation in 1961, there are rare findings
      about the effects of SOPH on reproductive system. In the present study, the
      pregnant mice administrated by different doses of SOPH were used to explore the
      effect of SOPH on embryo implantation, especially on the endometrial receptivity.
      The statistical results showed that the number of implanted embryos was gradually
      declining along the increasing dose of SOPH. When the administrated dose of SOPH
      was 600 mg/kg per day, great changes were observed in the exposed uterine
      morphology and up-regulated progesterone receptor (PR) and down-regulated
      estrogen receptor alpha (ERalpha), E-cadherin, matrix metalloproteinase-2 (MMP-2)
      and integrin beta3 were also found in SOPH-exposed uterine. These findings
      demonstrated that SOPH exposure reduced the number of implanted embryos in a dose
      dependent manner and failed the embryo implantation through altering the
      morphology of uterine and compromising the endometrial receptivity.

PMID- 24877641
TI  - Enhanced biocompatibility of PLGA nanofibers with gelatin/nano-hydroxyapatite
      bone biomimetics incorporation.
AB  - The biocompatibility of biomaterials is essentially for its application. The aim
      of current study was to evaluate the biocompatibility of poly(lactic-co-glycolic
      acid) (PLGA)/gelatin/nanohydroxyapatite (n-HA) (PGH) nanofibers systemically to
      provide further rationales for the application of the composite electrospun
      fibers as a favorable platform for bone tissue engineering. The PGH composite
      scaffold with diameter ranging from nano- to micrometers was fabricated by using
      electrospinning technique. Subsequently, we utilized confocal laser scanning
      microscopy (CLSM) and MTT assay to evaluate its cyto-compatibility in vitro.
      Besides, real-time quantitative polymerase chain reaction (qPCR) analysis and
      alizarin red staining (ARS) were performed to assess the osteoinductive activity.
      To further test in vivo, we implanted either PLGA or PGH composite scaffold in a
      rat subcutaneous model. The results demonstrated that PGH scaffold could better
      support osteoblasts adhesion, spreading, and proliferation and show better cyto
      compatibility than pure PLGA scaffold. Besides, qPCR analysis and ARS showed that
      PGH composite scaffold exhibited higher osteoinductive activity owing to higher
      phenotypic expression of typical osteogenic genes and calcium deposition. The
      histology evaluation indicated that the incorporation of
      Gelatin/nanohydroxyapatite (GH) biomimetics could significantly reduce local
      inflammation. Our data indicated that PGH composite electrospun nanofibers
      possessed excellent cyto-compatibility, good osteogenic activity, as well as good
      performance of host tissue response, which could be versatile biocompatible
      scaffolds for bone tissue engineering. 

PMID- 24877642
TI  - Highly sensitive quinoline-based two-photon fluorescent probe for monitoring
      intracellular free zinc ions.
AB  - Zn(2+) plays vital roles in regulating physiological and pathological processes.
      A number of diseases are associated with the disruption of intracellular free
      Zn(2+) homeostasis, and the relationship is still uncovered. Thus, it is
      important to monitor intracellular free Zn(2+) ions in real time, which is still
      challenging due to the low content of intracellular free Zn(2+). In this work, we
      report on the design and synthesis of a new two-photon (2P) fluorescent probe,
      QZn, based on quinoline derivative for intracellular free Zn(2+). Theoretical
      calculations were carried out to rationalize the design. The probe displayed a
      moderate 2P action cross section value of 51 GM at 820 nm and up to 10-fold
      fluorescence enhancement upon Zn(2+) binding. The detection limit of Zn(2+) was
      15.1 pM, which presented a pronounced sensitivity toward Zn(2+) and indicated
      that QZn would be competent for detecting the low-content intracellular Zn(2+).
      By using two-photon microscopy, QZn was capable of monitoring the fluctuation of
      intracellular free zinc ions in real time. 

PMID- 24877643
TI  - Structure and biological activities of an alginate from Sargassum fusiforme, and
      its sulfated derivative.
AB  - An alginate fraction, 04S2P, was isolated from the brown seaweed Sargassum
      fusiforme and was structurally characterized by the ratio (M/G) of beta-d
      mannuronic acid residues (M) to alpha-l-guluronic acid residues (G) via (1)H and
      (13)C NMR spectroscopy. When compared to commercial alginate (Alg) and alginates
      from other brown algae, 04S2P has a higher M/G ratio of 9.0:1.0 as determined by
      a modified high-performance liquid chromatography method after pre-column
      derivatization with PMP. Furthermore, the sulfated polysaccharides 04S2P-S and
      Alg-S were prepared by the chlorosulfonic acid-pyridine method. Both C-2 and/or C
      3 of M and G residues of 04S2P-S were substituted by sulfate groups, with C-3 of
      M residues preferentially substituted. Their effects on tube formation of HMEC-1
      cells were examined, and the results indicated that the sulfated Alg, Alg-S,
      exhibited a strong anti-angiogenic effect on HMEC-1 cells. The anti-tumor
      activity of native and sulfated alginates was tested on five different tumor cell
      lines. Alg-S demonstrated significant anti-tumor effects on the Bel7402,
      SMMC7721, and HT-29 cell lines, whereas 04S2P-S showed a distinct anti-tumor
      effect only on the Bel7402 cell line. 

PMID- 24877644
TI  - Rheological behaviour of nanocellulose reinforced unsaturated polyester
      nanocomposites.
AB  - Nanocellulose (NC) reinforced unsaturated polyester (UPR) composites were
      prepared by mechanical mixing process. Effect of isora nanocellulose on the
      properties of polyester composites has been studied in detail. Rheological
      properties of unsaturated polyester resin suspensions containing various amounts
      (0.5, 1 and 3wt%) of nanocellulose were investigated by oscillatory rheometer
      with parallel plate geometry. Analysis of curing revealed that the time required
      for gelation in NC filled UPR is lower than neat resin, which describe the
      catalytic action of NC on cure reaction. NC reinforced polyester suspensions
      showed shear thinning behaviour initially and at higher shear rates they showed
      Newtonian behaviour. Tensile and impact properties showed superior behaviour
      revealing improved interfacial bonding between nanofiller and the polymer matrix.
      With respect to the neat polyester the percentage increase in tensile strength of
      0.5wt% NC reinforced composite is 57%. Optical and atomic force microscopic
      studies confirmed that the dispersion state of NC within the polyester matrix was
      adequate. Maximum glass transition temperature is obtained for 0.5wt% NC
      reinforced composite, which showed an increase of 10 degrees C than neat resin. 

PMID- 24877645
TI  - Sulfated exopolysaccharide produced by Labrenzia sp. PRIM-30, characterization
      and prospective applications.
AB  - Exopolysaccharides (EPS) are biopolymers produced by bacteria, having potential
      industrial applications. An EPS produced by a bacterium designated as PRIM-30
      isolated from the deep seawater collected from offshore region of Cochin, India
      was studied. The isolate was identified as Labrenzia sp. based on 16S rRNA gene
      sequencing. Under optimum conditions for EPS production, the EPS yield was
      840mgL(-1) culture medium. The average molecular weight of the EPS was 269kDa and
      composed of glucose, arabinose, galacturonic acid and mannose in the ratio
      14.4:1.2:1:0.6. Importantly, the purified EPS contained 4.76% (w/w) sulfate
      groups. Viscosity of the (1% w/v) EPS was 3.92cP (shear rate 300s(-1), 25 degrees
      C). Anodic peak potential (Epa) of the EPS by cyclic voltametric measurement was 
      0.7V. The EPS showed antioxidant activities with IC50 values of 640 and 190MUgmL(
      1), respectively, for the inhibition of DPPH and superoxide radicals. The EPS
      displayed a linear dose dependent increase in total antioxidant capacity and
      ferric reducing power activities. To date, only a very few marine
      alphaproteobacterial representatives have been reported for EPS production and
      this study for the first time, shows the production of a sulfated EPS by a member
      of the genus Labrenzia. 

PMID- 24877646
TI  - Characterization of C-terminally engineered laccases.
AB  - Extremities of proteins are potent sites for functionalization. Carboxy terminus
      variants of the Trametes sp. strain C30 LAC3 laccase were generated and produced
      in Saccharomyces cerevisiae. A variant deleted of the last 13 residues (CDelta)
      and its 6 His tagged counterpart (CDelta6H) were found active enzymes. The
      production of CDelta6H resulted in the synthesis of a unusually high proportion
      of highly glycosylated forms of the enzyme therefore allowing the additional
      purification of a hyper-glycosylated form of CDelta6H noted CDelta6Hh. Properties
      of CDelta, CDelta6H and CDelta6Hh were compared. Globally, LAC3 catalytic
      efficiency was moderately affected by terminal modifications except in CDelta for
      which the kcat/KM ratio decreased 4 fold (with syringaldazine as substrate) and
      10 fold (with ABTS as substrate) respectively. The catalytic parameters kcat and
      KM of CDelta6H and CDelta6Hh were found to be strictly comparable revealing that
      over glycosylation does not affect the enzyme catalytic efficiency. To the
      contrary, in vitro deglycosylation of laccase drastically reduced its activity.
      So, despite a complex glycosylated pattern observed for some of the variant
      enzymes, terminal sequences of laccases appear to be appropriate sites for the
      functionalization/immobilization of laccase. 

PMID- 24877647
TI  - In vitro and in vivo analysis of the antithrombotic and toxicological profile of
      new antiplatelets N-acylhydrazone derivatives and development of nanosystems:
      determination of novel NAH derivatives antiplatelet and nanotechnological
      approach.
AB  - BACKGROUND: Cardiovascular diseases are the most frequent cause of morbidity and
      mortality worldwide. Among the most important cardiovascular diseases are
      atherothrombosis and venous thromboembolism that present platelet aggregation as
      a key event. Currently, the commercial antiplatelet agents display several
      undesirable effects, which prompt the search for new compounds with better
      therapeutic index, more efficient body distribution and mechanism. METHODS: In
      this work we characterized in vivo and in vitro the antithrombotic and
      toxicological profiles of novel antiplatelet N-substituted-phenylamino-5-methyl
      1H-1,2,3-triazole-4-carbohydrazides derivatives also comparing them with aspirin.
      In addition we also analyzed the stability of the more active compound after
      encapsulation in PLGA or PCL nanoparticles and the release profile of these new
      nanosystems. RESULTS: The biological results revealed not only the selective
      effect against arachidonic acid-induced platelet aggregation mainly for compounds
      2c, 2e and 2h but also their in vivo active profile on thromboembolism pulmonary
      animal model with better survival rates (e.g. 82%) than aspirin (33%). The
      overall toxicological profile was determined by in vitro (MTT reduction tests,
      neutral red uptake in kidney VERO cells and hemolysis assays) and in vivo
      (pulmonary embolism) assays that pointed 2c as the most promising derivative with
      potential as a lead compound. By using the nanoprecipitation technique 2c was
      loaded into PLGA and PCL nanoparticles showing controlled release profile over
      21days according to our drug release tests. CONCLUSION: According to our results
      compound 2c is the most interesting derivative for further studies as it showed
      the best activity and toxicological profile also allowing the nanoencapsulation
      process. Thus 2c may assist in determining a new potential therapy with favorable
      pharmacokinetics for treatment of thrombotic disorders.

PMID- 24877648
TI  - A latent reaction in a model GFP chromophore revealed upon confinement:
      photohydroxylation of ortho-halo benzylidene-3-methylimidazolidiones via an
      electrocylization process.
AB  - Excited state behavior of halogen substituted model GFP chromophores was
      investigated in an acetonitrile solution and in a confined environment provided
      by an octa acid capsule in water. Of the ortho, meta, and para halogen
      substituted GFP chromophores only the ortho compounds gave a new product
      resulting from an unprecedented photosubstitution of halogens by the hydroxyl
      group. This unusual reaction highlights the importance of confined spaces in
      bringing about some unattainable photoreactions. 

PMID- 24877649
TI  - Is less more? Lessons from aptamer selection strategies.
AB  - Aptamers have many inherent advantages originating from their in vitro selection
      and tailored chemical synthesis that makes them appealing alternatives of
      antibodies in bioaffinity assays. However, what ultimately matters, and that is
      the prerequisite to give way to all these advantages, is how well, and how
      selectively the aptamers bind to their targets. With the aptamer selection
      largely in the hand of life scientists, analytical chemists focused mostly on
      methodological development of aptamer-based assays using a fairly restricted
      number of aptamers to prove their concepts. However, ideally the development of
      an aptamer-based assay should start from the selection of aptamers to ensure
      their proper functionality in real samples. For instance information on the
      sample matrix can be implemented within counter-selection steps to discard
      aptamer candidates that show cross-reactivity to matrix components or critical
      interferents. In general, a larger consideration of the analytical use during
      selection and characterization of aptamers have been shown to increase the
      applicability of aptamers. Therefore, this review is a short, subjective view on
      trends in aptamer development highlighting factors to consider during their
      selection for a successful analytical application. 

PMID- 24877650
TI  - Short-term obesity results in detrimental metabolic and cardiovascular changes
      that may not be reversed with weight loss in an obese dog model.
AB  - The time course of metabolic and cardiovascular changes with weight gain and
      subsequent weight loss has not been elucidated. The goal of the present study was
      to determine how weight gain, weight loss and altered body fat distribution
      affected metabolic and cardiovascular changes in an obese dog model. Testing was
      performed when the dogs were lean (scores 4-5 on a nine-point scale), after ad
      libitum feeding for 12 and 32 weeks to promote obesity (>5 score), and after
      weight loss. Measurements included serum glucose and insulin, plasma leptin,
      adiponectin and C-reactive protein, echocardiography, flow-mediated dilation and
      blood pressure. Body fat distribution was assessed by computed tomography.
      Fasting serum glucose concentrations increased significantly with obesity (P<
      0.05). Heart rate increased by 22 (SE 5) bpm after 12 weeks of obesity (P=
      0.003). Systolic left ventricular free wall thickness increased after 12 weeks of
      obesity (P= 0.002), but decreased after weight loss compared with that observed
      in the lean phase (P= 0.03). Ventricular free wall thickness was more strongly
      correlated with visceral fat (r 0.6, P= 0.001) than with total body fat (r 0.4,
      P= 0.03) and was not significantly correlated with subcutaneous body fat (r 0.3,
      P= 0.1). The present study provides evidence that metabolic and cardiovascular
      alterations occur within only 12 weeks of obesity in an obese dog model and are
      strongly predicted by visceral fat. These results emphasise the importance of
      obesity prevention, as weight loss did not result in the return of all metabolic
      indicators to their normal levels. Moreover, systolic cardiac muscle thickness
      was reduced after weight loss compared with the pre-obesity levels, suggesting
      possible acute adverse cardiovascular effects.

PMID- 24877652
TI  - Development of a universal metabolome-standard method for long-term LC-MS
      metabolome profiling and its application for bladder cancer urine-metabolite
      biomarker discovery.
AB  - Large-scale metabolomics study requires a quantitative method to generate
      metabolome data over an extended period with high technical reproducibility. We
      report a universal metabolome-standard (UMS) method, in conjunction with chemical
      isotope labeling liquid chromatography-mass spectrometry (LC-MS), to provide long
      term analytical reproducibility and facilitate metabolome comparison among
      different data sets. In this method, UMS of a specific type of sample labeled by
      an isotope reagent is prepared a priori. The UMS is spiked into any individual
      samples labeled by another form of the isotope reagent in a metabolomics study.
      The resultant mixture is analyzed by LC-MS to provide relative quantification of
      the individual sample metabolome to UMS. UMS is independent of a study
      undertaking as well as the time of analysis and useful for profiling the same
      type of samples in multiple studies. In this work, the UMS method was developed
      and applied for a urine metabolomics study of bladder cancer. UMS of human urine
      was prepared by (13)C2-dansyl labeling of a pooled sample from 20 healthy
      individuals. This method was first used to profile the discovery samples to
      generate a list of putative biomarkers potentially useful for bladder cancer
      detection and then used to analyze the verification samples about one year later.
      Within the discovery sample set, three-month technical reproducibility was
      examined using a quality control sample and found a mean CV of 13.9% and median
      CV of 9.4% for all the quantified metabolites. Statistical analysis of the urine
      metabolome data showed a clear separation between the bladder cancer group and
      the control group from the discovery samples, which was confirmed by the
      verification samples. Receiver operating characteristic (ROC) test showed that
      the area under the curve (AUC) was 0.956 in the discovery data set and 0.935 in
      the verification data set. These results demonstrated the utility of the UMS
      method for long-term metabolomics and discovering potential metabolite biomarkers
      for diagnosis of bladder cancer. 

PMID- 24877651
TI  - Stable isotope dilution microquantification of creatine metabolites in plasma,
      whole blood and dried blood spots for pharmacological studies in mouse models of
      creatine deficiency.
AB  - BACKGROUND: To develop an accurate stable isotope dilution assay for simultaneous
      quantification of creatine metabolites ornithine, arginine, creatine, creatinine,
      and guanidinoacetate in very small blood sample volumes to study creatine
      metabolism in mice. METHODS: Liquid-chromatography (C18) tandem mass spectrometry
      with butylation was performed in positive ionization mode. Stable isotope
      dilution assay with external calibration was applied to three different specimen
      types, plasma, whole blood and dried blood spot (DBS). RESULTS: Analytical
      separation, sensitivity, accuracy, and linearity of the assay were adequate. The
      stable isotope dilution assay in plasma revealed no significant bias to gold
      standard methods for the respective analytes. Compared to plasma, we observed an
      overestimate of creatine and creatinine (2- to 5-fold and 1.2- to 2-fold,
      respectively) in whole-blood and DBS, and an underestimate of arginine (2.5-fold)
      in DBS. Validation of the assay in mouse models of creatine deficiency revealed
      plasma creatine metabolite pattern in good accordance with those observed in
      human GAMT and AGAT deficiency. Single dose intraperitoneal application of
      ornithine in wild-type mice lead to fast ornithine uptake (Tmax <= 10 min) and
      elimination (T1/2=24 min), and a decline of guanidinoacetate. CONCLUSION: The
      assay is fast and reliable to study creatine metabolism and pharmacokinetics in
      mouse models of creatine deficiency.

PMID- 24877653
TI  - Effect of channel layer thickness on the performance of indium-zinc-tin oxide
      thin film transistors manufactured by inkjet printing.
AB  - We report the fabrication of high field-effect mobility of ~110 cm(2)/(V s) for
      inkjet printed indium-zinc-tin oxide (IZTO) thin film transistors (TFTs). It is
      found that the morphology of IZTO material deposited by inkjet printing depends
      strongly on its thickness. When the thickness is 35 nm, IZTO is an homogeneous
      amorphous material and the TFT exhibits mobility over 100 cm(2)/(V s) and on/off
      current ratio of >10(6). However, when the thickness is 85 nm, IZTO has a two
      layer structure of homogeneous and heterogeneous materials and thus the TFT
      exhibited a mobility of ~20 cm(2)/(V s). When the thickness is 800 nm, the
      morphology is porous and heterogeneous and thus the on/off current ratio is less
      than 1 * 10(3) and its mobility is ~14 cm(2)/(V s). It is concluded therefore
      that homogeneous amorphous IZTO TFT on Al2O3 gate insulator can show high
      mobility, which can be achieved by thin layer formation by inkjet printing. 

PMID- 24877655
TI  - Amphioxus as a model for investigating evolution of the vertebrate immune system.
AB  - As the most basal chordate, the cephalochordate amphioxus has unique features
      that make it a valuable model for understanding the phylogeny of immunity.
      Vertebrate adaptive immunity (VAI) mediated by lymphocytes bearing variable
      receptors has been well-studied in mammals but not observed in invertebrates.
      However, the identification of lymphocyte-like cells in the gill along with genes
      related with lymphoid proliferation and differentiation indicates the presence of
      some basic components of VAI in amphioxus. Without VAI, amphioxus utilizes about
      10% of its gene repertoires, and an ongoing domain reshuffling mechanism among
      these genes, for innate immunity, suggesting extraordinary innate complexity and
      diversity not observed in other species. Innate diversity may not be comparable
      to the somatic diversity of the VAI, but there is no doubt of the success of this
      immune system, since amphioxus has existed for over 500 million years. Studies of
      amphioxus immunity may provide information on the reduction of innate immune
      complexity and the conflict between microbiota and host shaped the evolution of
      adaptive immune systems (AIS) during chordate evolution. 

PMID- 24877654
TI  - Pilot study of diet and microbiota: interactive associations of fibers and
      polyphenols with human intestinal bacteria.
AB  - Several studies have addressed the use of dietary fibers in the modulation of
      intestinal microbiota; however, information about other highly correlated
      components in foods, such as polyphenols, is scarce. The aim of this work was to
      explore the association between the intake of fibers and polyphenols from a
      regular diet and fecal microbiota composition in 38 healthy adults. Food intake
      was recorded using an annual food frequency questionnaire (FFQ). Quantification
      of microbial populations in feces was performed by quantitative PCR. A negative
      association was found between the intake of pectins and flavanones from oranges
      and the levels of Blautia coccoides and Clostridium leptum. By contrast, white
      bread, providing hemicellulose and resistant starch, was directly associated with
      Lactobacillus. Because some effects on intestinal microbiota attributed to
      isolated fibers or polyphenols might be modified by other components present in
      the same food, future research should be focused on diet rather than individual
      compounds. 

PMID- 24877657
TI  - Characterisation of chicken ZAP.
AB  - Emerging pathogenic viruses, such as avian influenza (AI), represent a serious
      threat to the poultry industry and human health. The development of novel
      therapeutics to protect against these viruses is critical and necessitates
      understanding the host immune mechanisms to find new pathways for protection
      against virus infection. Interferon (IFN) is a major antiviral arm of the immune
      system and is generally the first line of defence against virus. The multiple
      genes orchestrated by IFN upregulation are not well characterised in chickens due
      to a lack of reagents and research efforts. Here we have identified chicken ZAP
      (chZAP), an IFN stimulated gene (ISG), that has antiviral properties in human
      models, and show that chZAP is upregulated in response to PAMPs. Moreover, we
      show that chZAP is upregulated in vivo following particular viral infections.
      This data will benefit further studies that aim to understand antiviral response
      pathways in the chicken. 

PMID- 24877656
TI  - Molecular cloning and characterization of a new G-type lysozyme gene (Ec-lysG) in
      orange-spotted grouper, Epinephelus coioides.
AB  - Lysozyme acts as an innate immunity molecule against pathogen infection. In this
      study, a new G-type lysozyme gene with a typical G-type lysozyme domain
      (designated as Ec-lysG) was cloned and characterized from the orange-spotted
      grouper, Epinephelus coioides. The full-length Ec-lysG cDNA contains 1419 bp and
      encodes a 256-residue protein containing a 25-residue signal peptide at the N
      terminus. BLAST analysis reveals Ec-lysG shares 64% identity with Siniperca
      chuatsi, but 63% to another reported G-type lysozyme from orange-spotted grouper
      (OSG-lysG). The genomic DNA of Ec-lysG contains four exons and three introns,
      with a total length of 2062 bp. An amino acid sequence alignment showed that Ec
      lysG shares the fundamental structural features of G-type lysozyme, including the
      catalytic residues, substrate binding sites, and soluble lytic transglycosylase
      domain. Quantitative PCR showed that Ec-lysG transcript is most abundant in the
      head kidney, and less abundant in the heart. The expression of Ec-lysG was
      differentially upregulated in the head kidney after stimulation with
      lipopolysaccharide, Vibrio alginolyticus, and Singapore grouper iridovirus
      (SGIV). A subcellular localization analysis showed that Ec-lysG is distributed
      predominantly in the cytoplasm. Recombinant Ec-lysG (rEc-lysG) has optimal
      activity at pH 7.5 and 35 degrees C. rEc-lysG showed lytic activities against
      Gram-positive bacterium Streptococcus iniae, Staphylococcus aureus, and
      Micrococcus lysodeikticus, and the Gram-negative bacterium V. alginolyticus.
      Scanning electron microscopy (SEM) showed that rEc-lysG acts on M. lysodeikticus
      cell walls. The overexpression of Ec-lysG in grouper cells did not significantly
      delay the occurrence of the cytopathic effect (CPE) induced by SGIV, and did not
      inhibit viral gene transcription. In conclusion, Ec-lysG might be a potent
      antibacterial protein, with a role in innate immunity.

PMID- 24877659
TI  - The many faces of hemophagocytic lymphohistiocytosis - a challenge in diagnosis
      and therapy.

PMID- 24877658
TI  - Preliminary characterization of complement in a colonial tunicate: C3, Bf and
      inhibition of C3 opsonic activity by compstatin.
AB  - The complement system is a fundamental effector mechanism of the innate immunity
      in both vertebrates and invertebrates. The comprehension of its roots in the
      evolution is a useful step to understand how the main complement-related proteins
      had changed in order to adapt to new environmental conditions and life-cycles or,
      in the case of vertebrates, to interact with the adaptive immunity. Data on
      organisms evolutionary close to vertebrates, such as tunicates, are of primary
      importance for a better understanding of the changes in immune responses
      associated with the invertebrate-vertebrate transition. Here we report on the
      characterization of C3 and Bf transcripts from the colonial ascidian Botryllus
      schlosseri (BsC3 and BsBf, respectively), a reliable model organism for
      immunobiological research, and present a comparative analysis of amino acid
      sequences of C3s and Bfs suggesting that, in deuterostomes, the structure of
      these proteins remained largely unchanged. We also present new data on the cells
      responsible of the expression of BsC3 and BsBf showing that cytotoxic immunocytes
      are the sole cells where the relative transcripts can be found. Finally, using
      the C3 specific inhibitor compstatin, we demonstrate the opsonic role of BsC3 in
      accordance with the idea that promotion of phagocytosis is one of the main
      function of C3 in metazoans. 

PMID- 24877660
TI  - Effect of whole soy and purified isoflavone daidzein on renal function--a 6-month
      randomized controlled trial in equol-producing postmenopausal women with
      prehypertension.
AB  - OBJECTIVES: The aim of the study was to examine the long-term effect of commonly
      used whole soy foods (soy flour) and purified daidzein (one major isoflavone and
      the precursor of equol) on renal function among prehypertensive postmenopausal
      women who are also equol producers, a population most likely to benefit from soy
      intervention. DESIGN AND METHODS: This was a 6-month double-blind, randomized,
      placebo-controlled trial. Two hundred seventy eligible Chinese women were
      randomized to either one of the three treatments: 40 g soy flour (whole soy
      group), 40 g low-fat milk powder + 63 mg daidzein (daidzein group) or 40 g low
      fat milk powder (placebo group) daily each for 6 months. Fasting blood and 24-h
      urine samples were collected at the beginning and end of trial. Serum creatinine,
      cystatin C, urea, angiotensin-converting enzyme, minerals and 24-h urinary
      creatinine and minerals were analyzed. Estimated glomerular filtration rate
      (eGFR) was calculated with the Cockcroft-Gault and the Chronic Kidney Disease
      Epidemiology Collaboration (CKD-EPI) equations. RESULTS: Two hundred fifty-three
      subjects completed the study according to the protocol. Urinary isoflavones
      indicated good compliance of participants. No significant changes were observed
      in most of renal parameters, however, there was a less decrease in eGFRcockcroft
      in 6-month change (p=0.044) and %change (p=0.031) with whole soy intake relative
      to milk placebo. Subgroup analysis among women with lowered renal function
      suggested whole soy consumption tended to improve markers of renal function
      relative to control. CONCLUSIONS: Six-month consumption of whole soy tended to
      have a modest improvement of renal function in prehypertensive postmenopausal
      women with lowered renal function. Future trials in subjects with more declined
      renal function are necessary. TRIAL REGISTRATION: The trial was registered in
      ClinicalTrials.gov with identifier of NCT01270737. (URL:
      http://clinicaltrials.gov/ct2/show/NCT01270737).

PMID- 24877661
TI  - New insights into subtypes of invasive bladder cancer: considerations of the
      clinician.

PMID- 24877662
TI  - Re: Samira A. Brooks, A. Rose Brannon, Joel S. Parker, et al. Clear Code34: a
      prognostic risk predictor for localized clear cell renal cell carcinoma. Eur Urol
      2014;66:77-84.

PMID- 24877663
TI  - Dietary methionine availability affects the main factors involved in muscle
      protein turnover in rainbow trout (Oncorhynchus mykiss).
AB  - Methionine is a limiting essential amino acid in most plant-based ingredients of
      fish feed. In the present study, we aimed to determine the effect of dietary
      methionine concentrations on several main factors involved in the regulation of
      mRNA translation and the two major proteolytic pathways (ubiquitin-proteasome and
      autophagy-lysosomal) in the white muscle of rainbow trout (Oncorhynchus mykiss).
      The fish were fed for 6 weeks one of the three isonitrogenous diets providing
      three different methionine concentrations (deficient (DEF), adequate (ADQ) and
      excess (EXC)). At the end of the experiment, the fish fed the DEF diet had a
      significantly lower body weight and feed efficiency compared with those fed the
      EXC and ADQ diets. This reduction in the growth of fish fed the DEF diet was
      accompanied by a decrease in the activation of the translation initiation factors
      ribosomal protein S6 and eIF2alpha. The levels of the main autophagy-related
      markers (LC3-II and beclin 1) as well as the expression of several autophagy
      genes (atg4b, atg12 l, Uvrag, SQSTM1, Mul1 and Bnip3) were higher in the white
      muscle of fish fed the DEF diet. Similarly, the mRNA levels of several proteasome
      related genes (Fbx32, MuRF2, MuRF3, ZNF216 and Trim32) were significantly up
      regulated by methionine limitation. Together, these results extend our
      understanding of mechanisms regulating the reduction of muscle growth induced by
      dietary methionine deficiency, providing valuable information on the biomarkers
      of the effects of low-fishmeal diets.

PMID- 24877667
TI  - The prognostic role of circulating tumor cells in heavily pretreated individuals
      with a low life expectancy.
AB  - AIMS: Studies of circulating tumor cells (CTCs) have generally recruited
      individuals with newly diagnosed metastatic cancer, with recent data also
      indicating their prognostic value in the adjuvant setting. Their role in dying
      patients has not been established. EXPERIMENTAL: CTCs were measured in 43
      individuals with metastatic breast cancer estimated to have less than 6 months to
      live who had exhausted standard therapeutic options. RESULTS: Those with a CTC
      count of <= 100 had a median of 182 days to live, compared with those with a CTC
      count of >100 who had a median of 17 days until death (p = 0.009, log rank, HR:
      3.1, 95% CI: 1.4-7.3). CONCLUSION: A CTC count of >100 is associated with
      imminent death. Provided external validity is demonstrated, such information
      would be useful for patients and their families who often request specific
      prognostic clarity and could improve the quality of end-of-life care.

PMID- 24877668
TI  - N-Heterocyclic carbene-catalyzed chemoselective cross-aza-benzoin reaction of
      enals with isatin-derived ketimines: access to chiral quaternary aminooxindoles.
AB  - A chemo- and enantioselective cross-aza-benzoin reaction between enals and isatin
      derived ketimines is disclosed. The high chemoselectivity (of the acyl anion
      reaction over enal alpha- and beta-carbon reactions) is enabled by the electronic
      and steric properties of the N-heterocyclic carbene organocatalyst. 

PMID- 24877669
TI  - Enhanced salt-induced antioxidative responses involve a contribution of polyamine
      biosynthesis in grapevine plants.
AB  - The possible involvement of polyamines in the salt stress adaptation was
      investigated in grapevine (Vitis vinifera L.) plantlets focusing on
      photosynthesis and oxidative metabolism. Salt stress resulted in the
      deterioration of plant growth and photosynthesis, and treatment of plantlets with
      methylglyoxal-bis(guanylhydrazone) (MGBG), a S-adenosylmethionine decarboxylase
      (SAMDC) inhibitor, enhanced the salt stress effect. A decrease in PSII quantum
      yield (Fv/Fm), effective PSII quantum yield (Y(II)) and coefficient of
      photochemical quenching (qP) as well as increases in non-photochemical quenching
      (NPQ) and its coefficient (qN) was observed by these treatments. Salt and/or MGBG
      treatments also triggered an increase in lipid peroxidation and reactive oxygen
      species (ROS) accumulation as well as an increase of superoxide dismutase (SOD)
      and peroxidase (POX) activities, but not ascorbate peroxidase (APX) activity.
      Salt stress also resulted in an accumulation of oxidized ascorbate (DHA) and a
      decrease in reduced glutathione. MGBG alone or in combination with salt stress
      increased monodehydroascorbate reductase (MDHAR), SOD and POX activities and
      surprisingly no accumulation of DHA was noticed following treatment with MGBG.
      These salt-induced responses correlated with the maintaining of high level of
      free and conjugated spermidine and spermine, whereas a reduction of agmatine and
      putrescine levels was observed, which seemed to be amplified by the MGBG
      treatment. These results suggest that maintaining polyamine biosynthesis through
      the enhanced SAMDC activity in grapevine leaf tissues under salt stress
      conditions could contribute to the enhanced ROS scavenging activity and a
      protection of photosynthetic apparatus from oxidative damages. 

PMID- 24877670
TI  - Salt tolerance and activity of antioxidative enzymes of transgenic finger millet
      overexpressing a vacuolar H(+)-pyrophosphatase gene (SbVPPase) from Sorghum
      bicolor.
AB  - A vacuolar proton pyrophosphatase cDNA clone was isolated from Sorghum bicolor
      (SbVPPase) using end-to-end gene-specific primer amplification. It showed 80-90%
      homology at the nucleotide and 85-95% homology at the amino acid level with other
      VPPases. The gene was introduced into expression vector pCAMBIA1301 under the
      control of the cauliflower mosaic virus 35S (CaMV35S) promoter and transformed
      into Agrobacterium tumifaciens strain LBA4404 to infect embryogenic calli of
      finger millet (Eleusine coracana). Successful transfer of SbVPPase was confirmed
      by a GUS histochemical assay and PCR analysis. Both, controls and transgenic
      plants were subjected to 100 and 200mM NaCl and certain biochemical and
      physiological parameters were studied. Relative water content (RWC), plant
      height, leaf expansion, finger length and width and grain weight were severely
      reduced (50-70%), and the flowering period was delayed by 20% in control plants
      compared to transgenic plants under salinity stress. With increasing salt stress,
      the proline and chlorophyll contents as well as the enzyme activities of
      superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), guaiacol
      peroxidase (GPX) and glutathione reductase (GR) increased by 25-100% in
      transgenics, while malondialdehyde (MDA) showed a 2-4-fold decrease. The
      increased activities of antioxidant enzymes and the reduction in the MDA content
      suggest efficient scavenging of reactive oxygen species (ROS) in transgenics and,
      as a consequence, probably alleviation of salt stress. Also, the leaf tissues of
      the transgenics accumulated 1.5-2.5-fold higher Na(+) and 0.4-0.8-fold higher
      K(+) levels. Together, these results clearly demonstrate that overexpression of
      SbVPPase in transgenic finger millet enhances the plant's performance under salt
      stress. 

PMID- 24877671
TI  - Electrophysiological assessment of water stress in fruit-bearing woody plants.
AB  - Development and evaluation of a real-time plant water stress sensor, based on the
      electrophysiological behavior of fruit-bearing woody plants is presented.
      Continuous electric potentials are measured in tree trunks for different
      irrigation schedules, inducing variable water stress conditions; results are
      discussed in relation to soil water content and micro-atmospheric evaporative
      demand, determined continuously by conventional sensors, correlating this
      information with tree electric potential measurements. Systematic and
      differentiable patterns of electric potentials for water-stressed and no-stressed
      trees in 2 fruit species are presented. Early detection and recovery dynamics of
      water stress conditions can also be monitored with these electrophysiology
      sensors, which enable continuous and non-destructive measurements for efficient
      irrigation scheduling throughout the year. The experiment is developed under
      controlled conditions, in Faraday cages located at a greenhouse area, both in
      Persea americana and Prunus domestica plants. Soil moisture evolution is
      controlled using capacitance sensors and solar radiation, temperature, relative
      humidity, wind intensity and direction are continuously registered with accurate
      weather sensors, in a micro-agrometeorological automatic station located at the
      experimental site. The electrophysiological sensor has two stainless steel
      electrodes (measuring/reference), inserted on the stem; a high precision Keithley
      2701 digital multimeter is used to measure plant electrical signals; an algorithm
      written in MatLab((r)), allows correlating the signal to environmental variables.
      An electric cyclic behavior is observed (circadian cycle) in the experimental
      plants. For non-irrigated plants, the electrical signal shows a time positive
      slope and then, a negative slope after restarting irrigation throughout a rather
      extended recovery process, before reaching a stable electrical signal with zero
      slope. Well-watered plants presented a continuous signal with daily maximum and a
      minimum EP of similar magnitude in time, with zero slope. This plant electrical
      behavior is proposed for the development of a sensor measuring real-time plant
      water status. 

PMID- 24877672
TI  - Some synthetic cyclitol derivatives alleviate the effect of water deficit in
      cultivated and wild-type chickpea species.
AB  - Cyclitols were prepared from corresponding allylic hydroperoxides, synthesized by
      photooxygenation of the appropriate cyclic alkenes. These hydroperoxides were
      then separately treated with a catalytic amount of OsO4. Synthesized dl
      cyclopentane-1,2,3-triol 9 (A), dl-cyclohexane-1,2,3-triol 12 (B), and dl
      cycloheptane-1,2,3-triol 15 (C) were used in the investigation of plant stress.
      Antioxidants, lipid peroxidation, and water status of chickpea species exposed to
      synthetic cyclitols under water deficit were examined. Cyclitol derivatives
      significantly decreased leaf water potential, lipid peroxidation and H2O2 levels
      of wild and cultivated species under water deficit. Cyclitol treatments affected
      antioxidant enzyme activities differently in both species under water deficit.
      The highest SOD activity was found in A10-treated Cicer arietinum (cultivar) and
      C10-treated Cicer reticulatum (wild type) under water deficit. CAT activity
      increased in C. arietinum exposed to A cyclitols, while it increased slightly and
      then decreased in cyclitol-treated C. reticulatum under stress conditions. AP and
      GR activities were significantly increased in C. arietinum under water deficit.
      AP activity increased in C derivatives-treated C. arietinum, while it remained
      unchanged in C. reticulatum on day 1 of water deficit. GR activity was increased
      in A derivaties-treated C. arietinum and C derivatives-treated C. reticulatum on
      day 1 of water deficit and decreased with severity of stress (except for B10
      treated C. arietinum). The level of AsA in C treatments and GSH in A treatments
      increased in C. arietinum on day 1 of water deficit, while in C. reticulatum, AsA
      and GSH levels decreased under stress conditions. We conclude that exogenous
      synthetic cyclitol derivatives are biologically active and noncytotoxic,
      resulting in higher antioxidant activities and lower water potential, thus
      increasing the water deficit tolerance of chickpea under water deficit,
      especially of cultivated chickpea. We also propose that synthetic cyclitol
      derivatives can reduce reactive oxygen species and membrane damage and are
      beneficial for stress adaptation. 

PMID- 24877673
TI  - Cucumber Pti1-L is a cytoplasmic protein kinase involved in defense responses and
      salt tolerance.
AB  - Homologs of the cytoplasmic protein kinase Pti1 are found in diverse plant
      species. A clear role of Pti1 in plant defense response has not been established.
      We identified a Pti1 homolog in cucumber (CsPti1-L). CsPti1-L expression was
      induced when cucumber plants were challenged with the fungal pathogen
      Sphaerotheca fuliginea or with salt treatment. CsPti1-L expression in cucumber
      leaves also was induced by methyl jasmonate, salicylic acid, and abscisic acid.
      CsPti1-L exhibited autophosphorylation activity and was targeted to the
      cytoplasm. Transgenic Nicotiana benthamiana expressing CsPti1-L exhibited greater
      cell death and increased ion leakage in response to the bacterial pathogen
      Pseudomonas syringae pv. tomato DC3000, resistance to Botrytis cinerea infection,
      and higher tolerance to salt stress. RT-PCR analysis of transgenic N. benthamiana
      overexpressing CsPti1-L revealed constitutive upregulation of multiple genes
      involved in plant-defense and osmotic-stress responses. Our results suggest a
      functional role for CsPti1-L as a positive regulator of pathogen-defense and salt
      stress responses. 

PMID- 24877674
TI  - Abscisic acid metabolism and anthocyanin synthesis in grape skin are affected by
      light emitting diode (LED) irradiation at night.
AB  - The effects of blue and red light irradiation at night on abscisic acid (ABA)
      metabolism and anthocyanin synthesis were examined in grape berries. The
      expressions of VlMYBA1-2, VlMYBA2, UDP-glucose-flavonoid 3-O-glucosyltransferase
      (VvUFGT), 9-cis-epoxycarotenoid dioxygenase (VvNCED1), and ABA 8'-hydroxylase
      (VvCYP707A1) were also investigated. Endogenous ABA, its metabolite phaseic acid
      (PA), and the expressions of VvNCED1 and VvCYP707A1 were highest in red light
      emitting diode (LED)-treated skin. In contrast, anthocyanin concentrations were
      highest in blue LED-treated skin, followed by red LED treatment. However, the
      expressions of VlMYBA1-2, VlMYBA2, and VvUFGT did not necessarily coincide with
      anthocyanin concentrations. The quality of coloring may depend on the amount of
      malvidin-based anthocyanin, which increased toward harvest in blue and red LED
      treated skin, unlike in untreated controls. An increase in sugars was also
      observed in blue and red LED-treated skin. These results suggest that blue LED
      irradiation at night may be effective in increasing anthocyanin and sugar
      concentrations in grape berries. However, there is evidence that another factor
      may influence anthocyanin concentrations in grape berry skin significantly more
      than endogenous ABA: ABA concentrations were highest in red LED-treated skin,
      which had lower anthocyanin concentrations than blue LED-treated skin. 

PMID- 24877676
TI  - Rootstock alleviates PEG-induced water stress in grafted pepper seedlings:
      physiological responses.
AB  - Recent studies have shown that tolerance to abiotic stress, including water
      stress, is improved by grafting. In a previous work, we took advantage of the
      natural variability of Capsicum spp. and selected accessions tolerant and
      sensitive to water stress as rootstocks. The behavior of commercial cultivar
      'Verset' seedlings grafted onto the selected rootstocks at two levels of water
      stress provoked by adding 3.5 and 7% PEG (polyethylene glycol) was examined over
      14 days. The objective was to identify the physiological traits responsible for
      the tolerance provided by the rootstock in order to determine if the tolerance is
      based on the maintenance of the water relations under water stress or through the
      activation of protective mechanisms. To achieve this goal, various physiological
      parameters were measured, including: water relations; proline accumulation; gas
      exchange; chlorophyll fluorescence; nitrate reductase activity; and antioxidant
      capacity. Our results indicate that the effect of water stress on the measured
      parameters depends on the duration and intensity of the stress level, as well as
      the rootstock used. Under control conditions (0% PEG) all plant combinations
      showed similar values for all measured parameters. In general terms, PEG provoked
      a strong decrease in the gas exchange parameters in the cultivar grafted onto the
      sensitive accessions, as also observed in the ungrafted plants. This effect was
      related to lower relative water content in the plants, provoked by an inefficient
      osmotic adjustment that was dependent on reduced proline accumulation. At the end
      of the experiment, chronic photoinhibition was observed in these plants. However,
      the plants grafted onto the tolerant rootstocks, despite the reduction in
      photosynthetic rate, maintained the protective capacity of the photosynthetic
      machinery mediated by osmotic adjustment (based on higher proline content). In
      addition, water stress limited uptake and further NO3(-) transfer to the leaves.
      Increased nitrate reductase activity in the roots was observed, mainly in plants
      grafted onto the sensitive rootstocks, as well as the ungrafted plants, and this
      was associated with the lessened flux to the leaves. This study suggests that PEG
      induced water stress can be partially alleviated by using tolerant accessions as
      rootstocks. 

PMID- 24877675
TI  - Identification of quantitative trait loci for abscisic acid responsiveness in the
      D-genome of hexaploid wheat.
AB  - In crop species such as wheat, abiotic stresses and preharvest sprouting reduce
      grain yield and quality. The plant hormone abscisic acid (ABA) plays important
      roles in abiotic stress tolerance and seed dormancy. In previous studies, we
      evaluated ABA responsiveness of 67 Aegilops tauschii accessions and their
      synthetic hexaploid wheat lines, finding wide variation that was due to the D
      genome. In this study, quantitative trait locus (QTL) analysis was performed
      using an F2 population derived from crosses of highly ABA-responsive and less
      responsive synthetic wheat lines. A significant QTL was detected on chromosome
      6D, in a similar location to that reported for ABA responsiveness using
      recombinant inbred lines derived from common wheat cultivars Mironovskaya 808 and
      Chinese Spring. A comparative map and physiological and expression analyses of
      the 6D QTL suggested that this locus involved in line differences among wheat
      synthetics is different from that involved in cultivar differences in common
      wheat. The common wheat 6D QTL was found to affect seed dormancy and the
      regulation of cold-responsive/late embryogenesis abundant genes during
      dehydration. However, in synthetic wheat, we failed to detect any association of
      ABA responsiveness with abiotic stress tolerance or seed dormancy, at least under
      our experimental conditions. Development of near-isogenic lines will be important
      for functional analyses of the synthetic wheat 6D QTL. 

PMID- 24877677
TI  - Determination of abscisic acid and its glucosyl ester in embryogenic callus
      cultures of Vitis vinifera in relation to the maturation of somatic embryos using
      a new liquid chromatography-ELISA analysis method.
AB  - The levels of abscisic acid (ABA), its conjugate ABA-GE, and IAA were determined
      in embryogenic calli of Vitis vinifera L. (cv. Mencia) cultured in DM1
      differentiation medium, to relate them to the maturation process of somatic
      embryos. To achieve this goal, we developed an analytical method that included
      two steps of solid-phase extraction, chromatographic separation by HPLC, ABA-GE
      hydrolysis, and sensitive ELISA quantification. Because the ABA immunoassay was
      based on new polyclonal antibodies raised against a C4'-ABA conjugate, the assay
      was characterized (detection limit, midrange, measure range, and cross-reaction)
      and validated by a comparison of the ABA data obtained with this ELISA procedure
      and with a physicochemical method (LC-ESI-MS/MS). Radioactive-labeled internal
      standards were initially added to callus extracts to correct the losses of plant
      hormones, and thus assure the accuracy of the measurements. The endogenous
      concentration of ABA in the embryogenic callus cultured in DM1 medium was doubled
      at the fifth week of culture, concurring with the maturation process of somatic
      embryos, as indicated by the accumulation of carbohydrates observed through
      histological analysis. The ABA-GE content was higher than ABA, decreasing at 21
      days of culture in DM1 medium but increasing thereafter. The data suggest the
      involvement of the synthesis and conjugation of ABA in the final stages of
      development in grapevine somatic embryos from embryogenic callus. IAA levels were
      low, suggesting that auxin plays no significant role during the maturation of
      somatic embryos. In addition, the lower ABA levels in calli cultured in DM
      differentiation medium with PGRs, a medium presenting high precocious germination
      and deficiencies in somatic embryo development indicate that an increase in ABA
      content during the development of somatic embryos in grapevine is necessary for
      their correct maturation. 

PMID- 24877679
TI  - Effects of subchronic exposure of silver nanoparticles on intestinal microbiota
      and gut-associated immune responses in the ileum of Sprague-Dawley rats.
AB  - Silver nanoparticles (AgNP) are widely used for their antibacterial properties.
      Incorporation of AgNP into food-related products and health supplements
      represents a potential route for oral exposure to AgNP; however, the effects of
      such exposure on the gastrointestinal system are mostly unknown. This study
      evaluated changes in the populations of intestinal-microbiota and intestinal
      mucosal gene expression in Sprague-Dawley rats (both male and female) that were
      gavaged orally with discrete sizes of AgNP (10, 75 and 110 nm) and silver
      acetate. Doses of AgNP (9, 18 and 36 mg/kg body weight/day) and silver acetate
      (100, 200 and 400 mg/kg body weight/day) were divided and administered to rats
      twice daily (~10 h apart) for 13 weeks. The results indicate that AgNP prompted
      size- and dose-dependent changes to ileal-mucosal microbial populations, as well
      as, intestinal gene expression and induced an apparent shift in the gut
      microbiota toward greater proportions of Gram-negative bacteria. DNA-based
      analyses revealed that exposure to 10 nm AgNP and low-dose silver acetate caused
      a decrease in populations of Firmicutes phyla, along with a decrease in the
      Lactobacillus genus. Analysis of host gene expression demonstrated that smaller
      sizes and lower doses of AgNP exposure prompted the decreased expression of
      important immunomodulatory genes, including MUC3, TLR2, TLR4, GPR43 and FOXP3.
      Gender-specific effects to AgNP exposure were more prominent for the gut
      associated immune responses. These results indicate that the oral exposure to
      AgNP alter mucosa-associated microbiota and modulate the gut-associated immune
      response and the overall homeostasis of the intestinal tract.

PMID- 24877678
TI  - Origin of the different phytotoxicity and biotransformation of cerium and
      lanthanum oxide nanoparticles in cucumber.
AB  - To investigate how the physicochemical properties of nanoparticles (NPs) affect
      their biological and toxicological effects, we evaluated the phytotoxicity of
      CeO2 and La2O3 NPs to cucumber (Cucumis sativus) plants and tried to clarify the
      relation between physicochemical properties of NPs and their behaviors. CeO2 NPs
      had no phytotoxicity to cucumber at all tested concentrations, while La2O3 NPs
      showed significant inhibition on root elongation (>= 2 mg/L), shoot elongation
      (at 2000 mg/L), root biomass (>= 2 mg/L), and shoot biomass (>= 20 mg/L), as well
      as induced more reactive oxygen species and cell death in roots (2000 mg/L). The
      different distribution and speciation of Ce and La in plants were determined by
      synchrotron-based micro X-ray fluorescence microscopy and X-ray absorption
      spectroscopy. In the aerial parts, all of La was combined with phosphate or
      carboxylic group, while a fraction of Ce was changed to Ce(III)-carboxyl
      complexes, implying that La2O3 acted as its ionic form, while CeO2 displayed the
      behavior of particles or particle-ion mixtures. The higher dissolution of La2O3
      than CeO2 NPs might be the reason for their significant difference in
      phytotoxicity and transporting behaviors in cucumbers. To our knowledge, this is
      the first detailed study of the relation between the level of dissolution of NPs
      and their behaviors in plant systems.

PMID- 24877681
TI  - Small steps ... and leaps ... toward big science: multicenter studies in
      neuromuscular ultrasound.

PMID- 24877680
TI  - Mapping mental calculation systems with electrocorticography.
AB  - OBJECTIVE: We investigated intracranially-recorded gamma activity during
      calculation tasks to better understand the cortical dynamics of calculation.
      METHODS: We studied 11 patients with focal epilepsy (age range: 9-28years) who
      underwent measurement of calculation- and naming-related gamma-augmentation
      during extraoperative electrocorticography (ECoG). The patients were instructed
      to overtly verbalize a one-word answer in response to auditorily-delivered
      calculation and naming questions. The assigned calculation tasks were addition
      and subtraction involving integers between 1 and 17. RESULTS: Out of the 1001
      analyzed cortical electrode sites, 63 showed gamma-augmentation at 50-120Hz
      elicited by both tasks, 88 specifically during naming, and 7 specifically during
      calculation. Common gamma-augmentation mainly took place in the Rolandic regions.
      Calculation-specific gamma-augmentation, involving the period between the
      question-offset and response-onset, was noted in the middle-temporal, inferior
      parietal, inferior post-central, middle-frontal, and premotor regions of the left
      hemisphere. Calculation-specific gamma-augmentation in the middle-temporal,
      inferior-parietal, and inferior post-central regions peaked around the question
      offset, while that in the frontal lobe peaked after the question offset and
      before the response onset. This study failed to detect a significant difference
      in calculation-specific gamma amplitude between easy trials and difficult ones
      requiring multi-digit operations. CONCLUSIONS: Auditorily-delivered stimuli can
      elicit calculation-specific gamma-augmentation in multiple regions of the left
      hemisphere including the parietal region. However, the additive diagnostic value
      of measurement of gamma-augmentation related to a simple calculation task appears
      modest. SIGNIFICANCE: Further studies are warranted to determine the functional
      significance of calculation-specific gamma-augmentation in each site, and to
      establish the optimal protocol for mapping mental calculation.

PMID- 24877683
TI  - Clinically meaningful biomarkers for psychosis: a systematic and quantitative
      review.
AB  - Despite five decades of search for clinically meaningful 'biomarkers' in
      schizophrenia there are still no common tests to inform diagnosis or treatment.
      Our aim was to understand why it has been so difficult to convert biological
      findings into clinical tests. We categorized all PubMed-indexed articles
      investigating psychosis-related biomarkers to date (over 3200). Studies showed an
      evident publication bias, a confusing array of terminology, and few systematic
      efforts at longitudinal evaluation or external validation. Fewer than 200 studies
      investigated biomarkers, longitudinally, for prediction of illness course and
      treatment response. These biomarkers were then evaluated in terms of their
      statistical reliability and clinical effect size. Only one passed our a priori
      threshold for clinical applicability. This is a modest record. In order to
      promote real progress, the field needs: (a) consistent use of terminology so that
      studies can be compared; (b) a system of standardized universal reporting to
      overcome the existing publication bias; and (c) practical criteria [a prototype
      is suggested here] for assessing the clinical applicability of the findings. 

PMID- 24877682
TI  - Carpal tunnel syndrome impairs sustained precision pinch performance.
AB  - OBJECTIVE: The purpose of this study was to investigate effects of carpal tunnel
      syndrome (CTS) on digit force control during a sustained precision pinch.
      METHODS: Eleven CTS individuals and 11 age- and gender-matched healthy volunteers
      participated in the study. The subjects were instructed to isometrically pinch an
      instrumented apparatus for 60s with a stable force output. Visual feedback of
      force output was provided for the first 30s but removed for the remaining 30s.
      Pinch forces were examined for accuracy, variability, and inter-digit
      correlation. RESULTS: CTS led to a decrease in force accuracy and an increase in
      amount of force variability, particularly without visual feedback (p<0.001).
      However, CTS did not affect the structure of force variability or force
      correlation between digits (p>0.05). The force of the thumb was less accurate and
      more variable than that of the index finger for both the CTS and healthy groups
      (p<0.001). CONCLUSIONS: Sensorimotor deficits associated with CTS lead to
      inaccurate and unstable digit forces during sustained precision pinch.
      SIGNIFICANCE: This study shed light on basic and pathophysiological mechanisms of
      fine motor control and aids in development of new strategies for diagnosis and
      evaluation of CTS.

PMID- 24877684
TI  - Consequences of psychophysiological stress on cytochrome P450-catalyzed drug
      metabolism.
AB  - Most drugs are metabolized in the liver by cytochromes P450 (CYPs). Stress can
      modify CYP-catalyzed drug metabolism and subsequently, the pharmacokinetic
      profile of a drug. Current evidence demonstrates a gene-, stress- and species
      specific interference in stress-mediated regulation of genes encoding the major
      drug-metabolizing CYP isozymes. Stress-induced up-regulation of CYPs that
      metabolize the majority of prescribed drugs can result in their increased
      metabolism and consequently, in failure of pharmacotherapy. In contrast, stress
      induced down-regulation of CYP isozymes, including CYP2E1 and CYP2B1/2,
      potentially reduces metabolism of several toxicants and specific drugs-substrates
      resulting in increased levels and altered toxicity. The primary stress effectors,
      the adrenergic receptor-linked pathways and glucocorticoids, play primary and
      distinct roles in stress-mediated regulation of CYPs. Evidence demonstrates that
      stress regulates major drug metabolizing CYP isozymes, suggesting that stress
      should be considered to ensure pharmacotherapy efficacy and minimize drug
      toxicity. A detailed understanding of the molecular events underlying the stress
      dependent regulation of drug metabolizing CYPs is crucial both for the design of
      new drugs and for physiology-based pharmacokinetic and pharmacodynamic modeling. 

PMID- 24877685
TI  - Anomalous course and diameter of left-sided vertebral arteries--significance and
      predisposing factors in clinical practice.
AB  - INTRODUCTION: The purpose of this study was to determine whether any correlation
      exists between the level of entry of vertebral arteries (VAs) into the foramen
      transversarium (FT) and their anomalous course or diameter. To our knowledge
      there are no studies in the literature concerning the diameter of the vertebral
      artery (VA) as an impact factor on entrance level. MATERIAL AND METHODS: Computed
      tomography angiography (CTA) images of the aortic arch (AA) and its branches,
      obtained at the Department of Radiology, Medical University of Lodz from May 2009
      to April 2012, were reviewed and the entrance points into the FT were determined.
      RESULTS: Left vertebral arteries arising directly from the AA more often had an
      anomalous entrance point to the foramen transversarium and were more frequently
      hypoplastic. In addition, hypoplastic VAs entered the FT at an anomalous level
      more often than VAs with normal diameter. CONCLUSION: The left vertebral arteries
      arising directly from the aortic arch are often more hypoplastic and often enter
      the foramen transversarium at a different level from the C6 vertebrae. In
      patients with hypoplastic VA detected on the basis of ultrasound Color Doppler
      examination, the presence of anomalies must be considered when planning surgical
      treatment.

PMID- 24877686
TI  - The effect of screw preload and framework material on the success of cementable
      fixed partial prostheses: A finite element study.
AB  - The rigidity of framework materials and overload of the implant system directly
      affect the final transferred load of the bone around implants. The aim of the
      present study has been to analyse the influence of framework materials on the
      transferred load to the implant system and the surrounding bone. A finite element
      model of a long-span cementable implant-supported fixed prosthesis was created
      with two coping layers (gold and hybrid composite) to optimise the fitting of the
      prosthesis to the abutments. Three framework materials were analysed: titanium,
      gold alloy, and zirconia. The connection screws were first preloaded with 200 N.
      The framework was then loaded with 500 N vertically and at 30 degrees  to the
      framework long axis. Two loading conditions were considered: at the mesial and
      distal boundaries of the framework and at the centre of the framework. The
      stresses and strains within the framework materials and bone bed around the
      supporting implants were analysed. The region and angle of load applications
      showed an obvious effect on the values of the stresses and strains within the
      framework itself and, consequently, their distribution in the implant system and
      surrounding bone. A correlation of the framework material and stresses of the
      coping materials was observed as well. The gold framework showed acceptable
      values of stress within the cortical bone (92 MPa and 89 MPa with 30 degrees 
      loading at two points and at the centre, respectively) in comparison to titanium
      (92 MPa and 113 MPa) and zirconia (88 MPa and 115 MPa).

PMID- 24877687
TI  - Inhibition of peripheral anion exchanger 3 decreases formalin-induced pain.
AB  - We determined the role of chloride-bicarbonate anion exchanger 3 in formalin
      induced acute and chronic rat nociception. Formalin (1%) produced acute (first
      phase) and tonic (second phase) nociceptive behaviors (flinching and
      licking/lifting) followed by long-lasting evoked secondary mechanical allodynia
      and hyperalgesia in both paws. Local peripheral pre-treatment with the chloride
      bicarbonate anion exchanger inhibitors 4,4'-diisothiocyanatostilbene-2,2'
      disulfonic acid and 4-acetamido-4'-isothiocyanato-2,2'-stilbenedisulfonic acid
      prevented formalin-induced nociception mainly during phase 2. These drugs also
      prevented in a dose-dependent fashion long-lasting evoked secondary mechanical
      allodynia and hyperalgesia in both paws. Furthermore, post-treatment (on day 1 or
      6) with 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid reversed established
      hypersensitivity. Anion exchanger 3 was expressed in dorsal root ganglion neurons
      and it co-localized with neuronal nuclei protein (NeuN), substance P and
      purinergic P2X3 receptors. Furthermore, Western blot analysis revealed a band of
      about 85 kDa indicative of anion exchanger 3 protein expression in dorsal root
      ganglia of naive rats, which was enhanced at 1 and 6 days after 1% formalin
      injection. On the other hand, this rise failed to occur during 4,4'
      diisothiocyanatostilbene-2,2'-disulfonic acid exposure. These results suggest
      that anion exchanger 3 is present in dorsal root ganglia and participates in the
      development and maintenance of short and long-lasting formalin-induced
      nociception.

PMID- 24877688
TI  - Inhibition of adipocyte inflammation and macrophage chemotaxis by butein.
AB  - Adipose tissue inflammation has been proposed as a therapeutic target for the
      treatment of obesity and metabolic disorders such as insulin resistance and type
      2 diabetes. Butein, a polyphenol of vegetal origin, exhibits anti-inflammatory
      effects in macrophages but it was not reported whether butein prevents adipocyte
      inflammation. Here, we investigated the effects of butein on adipocyte
      inflammation in 3T3-L1 cells and performed functional macrophage migration
      assays. Butein opposed the stimulation of inducible nitric oxide synthase (iNOS)
      protein expression and of nitric oxide production by simultaneous treatment of
      adipocytes with tumor necrosis factor alpha (TNFalpha), lipopolysaccharide (LPS),
      and interferon gamma (TLI). In addition, butein inhibited mRNA expression of pro
      inflammatory genes and chemokines in adipocytes stimulated with TLI or
      conditioned medium from RAW 264.7 macrophages treated with LPS. These effects
      were associated with suppression of inhibitor of kappa B alpha degradation
      induced by TNFalpha and with nuclear factor-kappa B (NF-kappaB) p65
      phosphorylation and acetylation. Moreover, butein prevented phosphorylation of
      extracellular signal-regulated kinases, c-Jun N-terminal kinase, and the mitogen
      activated protein kinase (MAPK) p38. These results suggest that butein suppresses
      adipocyte inflammation by inhibiting NF-kappaB/MAPK-dependent transcriptional
      activity. Furthermore, conditioned media from adipocytes stimulated macrophage
      chemotaxis, whereas media from adipocytes treated with butein blocked macrophage
      migration, an effect that was consistent with suppression of MCP-1 secretion by
      adipocytes treated with butein. In addition, macrophages treated with butein
      exhibited a reduced ability to migrate toward adipocyte CM. In conclusion, butein
      may represent a therapeutic agent to prevent adipose tissue inflammation and the
      obesity-linked insulin resistance. 

PMID- 24877689
TI  - Mitochondrial protein targets of radiosensitisation by 1,8-dihydroxy-3-acetyl-6
      methyl-9,10 anthraquinone on nasopharyngeal carcinoma cells.
AB  - In our preliminary study, 1,8-dihydroxy-3-acetyl-6-methyl-9,10 anthraquinone
      (GXHSWAQ-1), synthesised according to the basic structure of emodin, exhibited a
      1.58-fold radiosensitisation on nasopharyngeal carcinoma CNE-1 cells. This study
      demonstrated that its radiosensitisation activity was achieved by altering the
      mitochondrial structure: swollen volume, fragmented crista, and decreasing
      transmembrane potential (P<0.01). Using isobaric tag for relative and absolute
      quantitation (iTRAQ) technology, 1396 proteins were identified, and the
      differentially expressed proteins were involved in metabolism, cell
      proliferation, angiogenesis, DNA repair process according to the biological
      process clustering results. Bioinformatic analysis showed that CDH1, RAC1, CDC42
      proteins might be mostly mitochondrial targets in the radiosensitisation process.
      Western blotting analyses verified the differential expression of these proteins.

PMID- 24877690
TI  - Tissue kallikrein (kallidinogenase) protects against retinal ischemic damage in
      mice.
AB  - Ocular ischemic syndrome is likely stem from retinal ischemia, and which causes
      visual disorder. The pathological mechanism of ocular ischemic syndrome is still
      unknown, therefore the optimal treatment for ocular ischemic syndrome remains to
      be established. Then, this study aimed to evaluate the effects of tissue-derived
      kallidinogenase in retinal ischemia protection in mice. In the present study, the
      effects of tissue-derived kallidinogenase (1 or 10 MUg/kg, i.v.) on
      ischemia/reperfusion-induced retinal damage in mice were examined by
      histological, electrophysiological, and permeability analyses. In addition, we
      assessed phosphorylation of endothelial nitric oxide synthase (eNOS) and nuclear
      factor-kappa B (NF-kappaB), which is closely-involved in ischemic injury and
      permeability. Moreover, the neuroprotective effect of kallidinogenase in an in
      vitro model of ischemia induced by oxygen-glucose deprivation or hypoxia was
      examined. The results indicated that kallidinogenase significantly prevented the
      decrease in ganglion cell number induced by ischemia/reperfusion.
      Electroretinogram measurements showed that kallidinogenase significantly
      prevented the ischemia/reperfusion-induced reductions in a- and b-wave amplitudes
      seen 5 days after ischemia/reperfusion. Moreover, kallidinogenase significantly
      inhibited the permeability increase induced by ischemia/reperfusion. Similar to
      the results in vivo, kallidinogenase significantly inhibited the retinal ganglion
      cell death induced by oxygen-glucose deprivation. Also, kallidinogenase
      significantly suppressed the hypoxia-induced increase in permeability. However,
      these effects observed in vitro disappeared when an eNOS inhibitor was used
      concurrently. These findings suggest that kallidinogenase may prevent
      ischemia/reperfusion-induced retinal damage, might be through eNOS activation.

PMID- 24877691
TI  - Zinc oxide nanoparticles, a novel candidate for the treatment of allergic
      inflammatory diseases.
AB  - Zinc (Zn) is an essential trace metal for eukaryotes. The roles of Zn in the
      numerous physiological functions have been elucidated. Bamboo salt contains Zn
      that was shown to have anti-inflammatory effect and other health benefits.
      Nanoparticles of various types have found application in the biology, medicine,
      and physics. Here we synthesized tetrapod-like, zinc oxide nanoparticles (ZO-NP;
      diameter 200 nm, source of Zn) using a radio frequency thermal plasma system and
      investigated its effects on mast cell-mediated allergic inflammatory reactions.
      ZO-NP was found to inhibit the productions and mRNA expressions of inflammatory
      cytokines such as interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha
      on the phorbol 12-myristate 13-acetate plus A23187 (PMACI)-stimulated human mast
      cell line, HMC-1 cells. In these stimulated cells, caspase-1 and nuclear factor
      kappaB activations were abolished by ZO-NP, and the expressions of receptor
      interacting protein2 (RIP2) and IkappaB kinasebeta (IKKbeta) induced by PAMCI
      were reduced. On the other hand, ZO-NP alone increased the expressions of RIP2
      and IKKbeta in normal condition. ZO-NP inhibited the phosphorylation of
      extracellular signal-regulated protein kinase in the PMACI-stimulated HMC-1
      cells. Furthermore, ZO-NP significantly inhibited passive cutaneous anaphylaxis
      activated by anti-dinitrophenyl IgE. These findings indicate that ZO-NP
      effectively ameliorates mast cell-mediated allergic inflammatory reaction, and
      suggest that ZO-NP be considered a potential therapeutic for the treatment of
      mast cell-mediated allergic diseases.

PMID- 24877693
TI  - Microvesicles mediate transfer of P-glycoprotein to paclitaxel-sensitive A2780
      human ovarian cancer cells, conferring paclitaxel-resistance.
AB  - The overexpression of P-glycoprotein (P-gp) causes resistance to chemotherapy in
      human ovarian cancer. However, the underlying mechanism remains unclear. In the
      present study, we showed that, at membrane-bound protein level, P-gp was 'shared'
      between human ovarian cancer cells by the intercellular transfer of microvesicles
      (MVs). Paclitaxel-resistant human ovarian cancer cells (A2780/PTX) readily formed
      and released P-gp-containing MVs into the extracellular space compared with the
      wild-type parental line (A2780/WT). Shedding MVs bound to the chemosensitive
      A2780/WT cells in a time- and dose-dependent manner, transferring P-gp via the
      microenvironment. MV-mediated transfer of P-gp led to redistribution of the
      chemotherapeutic drug adriamycin in recipient cells (A2780/WT), which displayed 5
      and 5-fold higher resistance to adriamycin and paclitaxel, respectively. Thus,
      these findings demonstrate a new mechanism of drug-resistance acquisition via
      MVs. 

PMID- 24877692
TI  - Protective effect of linarin against D-galactosamine and lipopolysaccharide
      induced fulminant hepatic failure.
AB  - Linarin was isolated from Chrysanthemum indicum L. Fulminant hepatic failure is a
      serious clinical syndrome that results in massive inflammation and hepatocyte
      death. Apoptosis is an important cellular pathological process in d-galactosamine
      (GalN)/lipopolysaccharide (LPS)-induced liver injury, and regulation of liver
      apoptosis might be an effective therapeutic method for fulminant hepatic failure.
      This study examined the cytoprotective mechanisms of linarin against GalN/LPS
      induced hepatic failure. Mice were given an oral administration of linarin (12.5,
      25 and 50mg/kg) 1h before receiving GalN (800 mg/kg)/LPS (40 MUg/kg). Linarin
      treatment reversed the lethality induced by GalN/LPS. After 6h of GalN/LPS
      injection, the serum levels of alanine aminotransferase, aspartate
      aminotransferase, tumor necrosis factor (TNF)-alpha, interleukin-6 and interferon
      gamma were significantly elevated. GalN/LPS increased toll-like receptor 4 and
      interleukin-1 receptor-associated kinase protein expression. These increases were
      attenuated by linarin. Linarin attenuated the increased expression of Fas
      associated death domain and caspase-8 induced by GalN/LPS, reduced the cytosolic
      release of cytochrome c and caspase-3 cleavage induced by GalN/LPS, and reduced
      the pro-apoptotic Bim phosphorylation induced by GalN/LPS. However, linarin
      increased the level of anti-apoptotic Bcl-xL and phosphorylation of STAT3. Our
      results suggest that linarin alleviates GalN/LPS-induced liver injury by
      suppressing TNF-alpha-mediated apoptotic pathways.

PMID- 24877694
TI  - Antiviral activity of aloe-emodin against influenza A virus via galectin-3 up
      regulation.
AB  - Novel influenza A H7N9 virus, which emerged in 2013, and highly pathogenic H5N1
      virus, identified since 2003, pose challenges to public health and necessitate
      quest for new anti-influenza compounds. Anthraquinone derivatives like aloe
      emodin, emodin and chrysophanol, reportedly exhibit antiviral activity. This
      study probes their inhibitory mechanism and effect against influenza A virus. Of
      three anthraquinone derivatives, aloe-emodin, with a lower cytotoxicity showed
      concentration-dependently reducing virus-induced cytopathic effect and inhibiting
      replication of influenza A in MDCK cells. 50% inhibitory concentration value of
      aloe-emodin on virus yield was less than 0.05 MUg/ml. Proteomics and Western blot
      of MDCK cells indicated aloe-emodin up-regulating galectin-3, and thioredoxin as
      well as down-regulating nucleoside diphosphate kinase A. Western blot and
      quantitative PCR confirmed aloe-emodin up-regulating galectin-3 expression;
      recombinant galectin-3 augmented expression of antiviral genes IFN-beta, IFN
      gamma, PKR and 2'5',-OAS in infected cells, agreeing with expression pattern of
      those treated with aloe-emodin. Galectin-3 also inhibited influenza A virus
      replication. Proteomic analysis of treated cells indicated galectin-3 up
      regulation as one anti-influenza A virus action by aloe-emodin. Since galectin-3
      exhibited cytokine-like regulatory actions via JAK/STAT pathways, aloe-emodin
      also restored NS1-inhibited STAT1-mediated antiviral responses in transfected
      cells: e.g., STAT1 phosphorylation of interferon (IFN) stimulation response
      element (ISRE)-driven promoter, RNA-dependent protein kinase (PKR) and 2'5',
      oligoadenylate synthetase (2'5',-OAS) expression. Treatment with aloe-emodin
      could control influenza infection in humans.

PMID- 24877695
TI  - Study of the surfactant properties of aqueous stream from the corn milling
      industry.
AB  - Corn steep liquor (CSL) is a liquid byproduct generated by the corn wet-milling
      industry. This agroindustrial residue is obtained when corn is digested with warm
      water and SO2 in the presence of different spontaneously growing microorganisms.
      The microbial population of CSL includes lactic acid bacteria, which are widely
      known to produce biosurfactants. However, there is no information available about
      the possible existence of surface-active compounds in CSL. In this work the
      surface tension activity of CSL was evaluated and the biosurfactant contained in
      this residue was extracted with different organic solvents and characterized. The
      biosurfactant obtained from CSL was analyzed by Fourier transform infrared
      spectroscopy, and the composition in fatty acid was analyzed by gas
      chromatography-mass spectrometry. The hydrophobic chain of the biosurfactant
      contained in CSL comprised 50-55.2% linolelaidic acid, 15.7-22.2% oleic and/or
      elaidic acid, 5.9-14.6% stearic acid, and 14.9-19.6% palmitic acid. 

PMID- 24877696
TI  - Association of synchronous medullary and papillary thyroid carcinomas with
      primary hyperparathyroidism: first case report and literature review.
AB  - OBJECTIVE: We report a case of a patient with symptomatic primary
      hyperparathyroidism who was found, through a thorough radiological investigation,
      to also have papillary and medullary thyroid carcinomas. CASE REPORT: A 59-year
      old female was diagnosed with primary hyperparathyroidism. A further radiological
      investigation found suspicious areas within both thyroid lobes that were later
      diagnosed as foci of papillary and medullary thyroid carcinomas. Appropriate
      treatment was commenced. Reports of similar occurrences of synchronous thyroid
      and parathyroid pathologies are discussed. CONCLUSION: To our knowledge, this is
      the first reported case of two synchronous thyroid cancers occurring in the
      context of primary hyperparathyroidism. We strongly recommend a thorough
      radiological investigation of all patients with primary hyperparathyroidism to
      prevent missing concurrent thyroid cancers.

PMID- 24877701
TI  - A content analysis of cognitive and affective uses of patient support groups for
      rare and uncommon vascular diseases: comparisons of may thurner, thoracic outlet,
      and superior mesenteric artery syndrome.
AB  - Rare disease patients are the predominant group of patients who are now
      connecting online to patient support groups, yet research on their uses of
      support groups has received little attention. This is a content analysis of three
      vascular diseases of differing degrees of rarity. Wall posts from Facebook
      patient support groups for May Thurner syndrome, thoracic outlet syndrome, and
      superior mesenteric artery syndrome were analyzed over a period of two years.
      Using Uses and Gratifications as the theoretical framework, the study purpose was
      to assess how variations in health condition and rarity of condition affect
      online support group user needs. Results indicated common main cognitive and
      affective uses across conditions, indicating a consistent pattern of needs
      communicated by all patients. However, there were nuanced differences in
      subcategories of cognitive and affective uses between the most and least rare
      disorders, which inform areas for tailored support mechanisms. Additionally,
      these vascular patients used their respective support groups primarily for
      cognitive reasons, especially for the rarest conditions, which informs of basic
      medical informational needs these patients face related to tests, treatment,
      surgery, and diagnoses. 

PMID- 24877702
TI  - Assessment of the paraphilias.
AB  - Paraphilias are recurrent, persistent, and intense sexual interests in atypical
      objects or activities. The most commonly encountered paraphilias in sexological
      or forensic settings are pedophilia, sexual sadism, exhibitionism, and voyeurism.
      Paraphilias are often comorbid with other sexual, mood, and personality
      disorders. Assessment and diagnosis require an integration of multiple sources of
      clinical information, given the limits and biases of self-report (through
      clinical interview or questionnaires). Clinicians ideally have access to more
      objective assessment methods, such as phallometric testing of sexual arousal. The
      accurate assessment and diagnosis of paraphilias is essential to effective
      treatment and management. 

PMID- 24877703
TI  - Psychological treatment of sex offenders: recent innovations.
AB  - This article describes recent innovations in the psychological treatment of sex
      offenders. These recent innovations include the incorporation of Andrews and
      Bonta's RNR Principles, Ward's "Good Lives Model," and Miller and Rollnick's
      Motivational Interviewing into a strength-based approach. An example of a
      strength-based treatment program is described and treatment outcome evaluations
      are summarized.

PMID- 24877704
TI  - Pharmacologic treatment of paraphilias.
AB  - The treatment of paraphilias remains a challenge in the mental health field.
      Combined pharmacologic and psychotherapeutic treatment is associated with better
      efficacy. The gold standard treatment of severe paraphilias in adult males is
      antiandrogen treatment with cognitive behavioral therapy. Selective serotonin
      reuptake inhibitors have been used in mild types of paraphilia and in cases of
      sexual compulsions and juvenile paraphilias. Antiandrogen treatments seem to be
      effective in severe paraphilic subjects committing sexual offenses. In
      particular, gonadotropin-releasing hormone analogs have shown high efficacy
      working in a similar way to physical castration but being reversible at any time.
      Treatment recommendations, side effects, and contraindications are discussed. 

PMID- 24877705
TI  - Mental illness and sexual offending.
AB  - Transinstitutionalization (ie, the criminalization of those with mental illness)
      is relevant to individuals committing sexual offenses. Mental illness can affect
      the treatment and risk management of individuals committing sexual offenses. In
      this article the current literature on mentally disordered sexual offenders is
      described, including how psychosis, mood disorders, anxiety disorders, attention
      deficit/hyperactivity disorder, and dementing disorders may affect treatment and
      management. 

PMID- 24877706
TI  - Persons with intellectual disabilities and problematic sexual behaviors.
AB  - Persons with intellectual disabilities who have been identified because they
      committed a sexual offense may have done so because of a sexual paraphilia.
      However, special consideration in assessment is required to determine whether the
      offense is caused by a paraphilia alone or whether other factors relating to the
      individual's intellectual disabilities may be especially significant. This
      article reviews some factors that have been identified as significant and
      provides an overview of treatment approaches from multiple perspectives. 

PMID- 24877707
TI  - Treatment and management of child pornography use.
AB  - Advances in Internet and other digital technologies have created ready and
      affordable access to pornography involving real children or computer-generated
      images of children. To better understand and manage child pornography users,
      clinicians must acquaint themselves with the characteristics and behaviors of
      these offenders. This article distinguishes motivations to use child pornography
      and different types of child pornography offenders and provides a brief overview
      of the assessment, diagnosis, and management options available. The authors
      conclude with recommendations on future directions in the assessment, diagnosis,
      and management of child pornography offenders. 

PMID- 24877708
TI  - Sexual sadism in sexual offenders and sexually motivated homicide.
AB  - This article gives a clinically oriented overview of forensically relevant forms
      of sexual sadism disorder and its specific relationship to sexual homicide. In
      sexual homicide perpetrators, peculiar patterns of sexual sadism may be a
      motivational pathway to kill. Sexual sadism increases the risk for reoffending in
      sexual offenders. Through psychotherapy and pharmacological interventions,
      treatment of sadistic sex offenders has to consider special characteristics that
      may be different from those of nonsadistic sex offenders. Many of these offenders
      share a combination of sexual sadistic motives and an intact self-regulation,
      sometimes combined with a high level of sexual preoccupation. 

PMID- 24877709
TI  - Dysfunctional anger and sexual violence.
AB  - Sexual offenses with or without aggression attract attention from the popular
      media and the scientific community. Empirical research suggests a relationship
      between anger and sexual violence. This article describes the key themes of
      dysfunctional anger and sexual violence, and how dysfunctional anger relates to
      sexual fantasies, sexual offending, and sexual recidivism. The implications of
      the findings for clinical practice and future research are discussed. 

PMID- 24877710
TI  - Ethics and the treatment of sexual offenders.
AB  - Clinicians in sex offender treatment programs always encounter the need to
      balance the best interests of sex offenders and the safety needs of the
      community. The protection of the community often takes primacy, resulting in
      violation of traditional mental health codes of ethics. These ethical dilemmas
      have generated debates in the academic community. To minimize ethical dilemmas,
      clinicians in sex offender treatment programs need to acknowledge the conflicts,
      adhere to safeguards, and thoughtfully address the challenges with profession
      specific ethical values and codes. This article reviews ethical principles in
      relation to conceptualization of sex offenders and their assessment and treatment
      and research involving sex offenders. 

PMID- 24877711
TI  - The natural history of the paraphilias.

PMID- 24877712
TI  - Immunomodulation mediated by a herbal syrup containing a standardized Echinacea
      root extract: a pilot study in healthy human subjects on cytokine gene
      expression.
AB  - In this study, the immunomodulatory effect of a triply standardized Echinacea
      angustifolia root extract (Polinacea((r))) was evaluated in 10 healthy subjects.
      Ten ml of syrup containing one hundred mg of extract (corresponding to 4.7 mg of
      Echinacoside and 8.0mg of a high molecular weight-20,000 Da- polysaccharide) were
      administered as a herbal syrup once a day for one month. The immunomodulatory
      effect was evaluated before and after herbal syrup administration evaluating the
      expression levels of the cytokines IL-2, IL-8, IL-6 and TNF-alpha. Cytokine
      expression was studied in lympho-monocytes and in plasma samples measuring the
      mRNA and protein levels, respectively. The results were analysed by ANOVA and non
      parametric Friedman rank sum tests; when possible it was adopted a pair-wise
      comparisons at different post-treatment times, using the paired t-tests with Holm
      correction. The correlation between the variations of cytokine plasma levels and
      the respective mRNA was carried out using a linear regression model. In lympho
      monocytes our data indicate the up-regulation of the mRNA levels of IL-2 and IL-8
      and the down regulation of the mRNA levels of the pro-inflammatory cytokines TNF
      alpha and IL6. The differential regulation was maximal after 14 days of
      treatment. IL-2 up-regulation and IL-6 down-regulation were also confirmed at the
      protein level in plasma. Finally, the up-regulation of the mRNA of IL-2/IL-8 and
      the down-regulation of IL-6 positively correlated with the protein levels
      detected in the plasma. In conclusion, this pilot study suggests a relevant role
      for the standardized Echinacea angustifolia root extract in the control of
      cytokine expression. This first demonstration of the immuno-modulating activity
      of Echinacea angustifolia root extract in the healthy subject, supports at least
      in part the common use of such products as health promoting supplement.

PMID- 24877713
TI  - A heteroglycan from the cyanobacterium Nostoc commune modulates LPS-induced
      inflammatory cytokine secretion by THP-1 monocytes through phosphorylation of
      ERK1/2 and Akt.
AB  - Cyanobacteria (blue-green algae) have been consumed as food and used in folk
      medicine since ancient times to alleviate a variety of diseases. Cyanobacteria of
      the genus Nostoc have been shown to produce complex exopolysaccharides with
      antioxidant and antiviral activity. Furthermore, Nostoc sp. are common in
      cyanolichen symbiosis and lichen polysaccharides are known to have
      immunomodulating effects. Nc-5-s is a heteroglycan isolated from free-living
      colonies of Nostoc commune and its structure has been characterized in detail.
      The aim of this study was to determine the effects of Nc-5-s on the inflammatory
      response of lipopolysaccharide (LPS)-stimulated human THP-1 monocytes and how the
      effects are mediated. THP-1 monocytes primed with interferon-gamma and stimulated
      with LPS in the presence of Nc-5-s secreted less of the pro-inflammatory cytokine
      interleukin (IL)-6 and more of the anti-inflammatory cytokine IL-10 than THP-1
      monocytes stimulated without Nc-5-s. In contrast, Nc-5-s increased LPS-induced
      secretion of the pro-inflammatory cytokines tumor necrosis factor (TNF)-alpha and
      IL-8. Nc-5-s decreased LPS-induced phosphorylation of the extracellular regulated
      kinase (ERK)1/2 and Akt kinase, but did not affect phosphorylation of the p38
      kinase, activation of the nuclear factor kappa B pathway, nor DNA binding of c
      fos. These results show that Nc-5-s has anti-inflammatory effects on IL-6 and IL
      10 secretion by THP-1 monocytes, but its effects are pro-inflammatory when it
      comes to TNF-alpha and IL-8. Furthermore, they show that the effects of Nc-5-s
      may be mediated through the ERK1/2 pathway and/or the Akt/phosphoinositide 3
      kinase pathway and their downstream effectors. The ability of Nc-5-s to decrease
      IL-6 secretion, increase IL-10 secretion and moderate ERK1/2 activation indicates
      a potential for its development as an anti-inflammatory agent. 

PMID- 24877714
TI  - Effect of Tenuifoliside A isolated from Polygala tenuifolia on the ERK and PI3K
      pathways in C6 glioma cells.
AB  - Tenuifoliside A (TFSA) is a bioactive oligosaccharide ester component of Polygala
      tenuifolia Wild, a traditional Chinese medicine which was used to manage mental
      disorders effectively. The neuroprotective and anti-apoptotic effects of TFSA
      have been demonstrated in our previous studies. The present work was designed to
      study the molecular mechanism of TFSA on promoting the viability of rat glioma
      cells C6. We exposed C6 cells to TFSA (or combined with ERK, PI3K and TrkB
      inhibitors) to examine the effects of TFSA on the cell viability and the
      expression and phosphorylation of key proteins in the ERK and PI3K signaling
      pathway. TFSA increased levels of phospho-ERK and phospho-Akt, enhanced release
      of BDNF, which were blocked by ERK and PI3K inhibitors, respectively (U0126 and
      LY294002). Moreover, the TFSA caused the enhanced phosphorylation of cyclic AMP
      response element binding protein (CREB) at Ser133 site, the effect was revoked by
      U0126, LY294002 and K252a. Furthermore, when C6 cells were pretreated with K252a,
      a TrkB antagonist, known to significantly inhibit the activity of brain-derived
      neurotrophic factor (BDNF), blocked the levels of phospho-ERK, phospho-Akt and
      phosphor-CREB. Taking these results together, we suggested the neuroprotection of
      TFSA might be mediated through BDNF/TrkB-ERK/PI3K-CREB signaling pathway in C6
      glioma cells. 

PMID- 24877715
TI  - Hepatoprotective activity of LC-ESI-MS standardized Iris spuria rhizome extract
      on its main bioactive constituents.
AB  - The study was designed to evaluate the hepatoprotective activity of Iris spuria
      against paracetamol induced toxicity at two different doses 100 and 200 mg/kg.
      The extract showed significant protective activity (p>0.01) at both the doses in
      dose dependent manner. Administration of the plant extract restored the
      paracetamol induced elevated levels of serum marker and distorted hepatic tissue
      architecture. The lipid peroxides (LPO) and glutathione (GSH) levels were also
      restored towards normal in liver tissue significantly. The main chemical
      constituents of the extract identified by the liquid chromatography-tandem mass
      spectrometry (LC-ESI-MSMS) were found to be flavones and isoflavonoids.
      Tectoridin and iristectorigenin A were the principal compounds present in the
      methanolic extract of Iris spuria.

PMID- 24877716
TI  - Ginkgo biloba extract for essential hypertension: a systemic review.
AB  - BACKGROUND: Ginkgo biloba extract (GBE), a traditional natural herbal product, is
      often used in the treatment of essential hypertension (EH) as complementary
      therapy in China and European countries. AIM: To critically assess the current
      clinical evidence of efficacy and safety of GBE for EH. METHODS: 7 electronic
      databases (Cochrane Library, PubMed, EMBASE, VIP, CBM, Wanfang data, and CNKI)
      were searched to identify randomized controlled trials (RCTs) of GBE for EH.
      Methodological quality was assessed independently using the Cochrane Handbook for
      Systematic Reviews of Interventions. RESULTS: A total of 9 RCTs with 1012
      hypertensive patients were identified and reviewed. Most RCTs were of high risk
      of bias with flawed study design and poor methodological quality. 6 trials
      demonstrated potential positive effect of GBE as complementary therapy on BP
      reduction when compared with antihypertensive drug therapy; however, it was not
      associated with a statistically significant effect on both SBP and DBP reduction
      in 3 other trials. Despite the positive findings, there were so many
      methodological limitations and significant clinical heterogeneity. Most of the
      trials did not report adverse effects, and the safety of GBE is still uncertain.
      CONCLUSION: No confirmative conclusions on the efficacy and safety of GBE for EH
      could be drawn. More rigorous trials are warranted to support their clinical use.

PMID- 24877718
TI  - The cooked meat-derived mammary carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5
      b]pyridine (PhIP) elicits estrogenic-like microRNA responses in breast cancer
      cells.
AB  - The cooking of meat results in the generation of heterocyclic amines (HCA), the
      most abundant of which is 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP).
      Data from epidemiological, mechanistic, and animal studies indicate that PhIP
      could be causally linked to breast cancer incidence. Besides the established DNA
      damaging and mutagenic activities of PhIP, the chemical is reported to have
      oestrogenic activity that could contribute to its tissue specific
      carcinogenicity. In this study we investigated the effect of treatment with PhIP
      and 17-beta-estradiol (E2) on global microRNA (miRNA) expression of the oestrogen
      responsive MCF-7 human breast adenocarcinoma cell line. PhIP and E2 caused
      widespread and largely over-lapping effects on miRNA expression, with many of the
      commonly affected miRNA reported to be regulated by oestrogen and have been
      implicated in the initiation and progression of breast cancer. The regulatory
      activity of the miRNAs we show here to be responsive to PhIP treatment, are also
      predicted to mediate cellular phenotypes that are associated with PhIP exposure.
      Consequently, this study offers further support to the ability of PhIP to induce
      widespread effects via activation of oestrogen receptor alpha (ERalpha).
      Moreover, this study indicates that deregulation of miRNA by PhIP could
      potentially be an important non-DNA-damaging carcinogenic mechanism in breast
      cancer. 

PMID- 24877719
TI  - Chemoproteomics reveals time-dependent binding of histone deacetylase inhibitors
      to endogenous repressor complexes.
AB  - Class I histone deacetylases (HDACs) are attractive drug targets in oncology and
      inflammation. However, the development of selective inhibitors is complicated by
      the characteristic that the localization, activity, and selectivity of class I
      HDACs are regulated by association in megadalton repressor complexes. There is
      emerging evidence that isoform and protein complex selectivity can be achieved by
      aminobenzamide inhibitors. Here we present a chemoproteomics strategy for the
      determination of time-dependent inhibitor binding to endogenous HDACs and HDAC
      complexes. This approach enabled us to determine kinetic association and
      dissociation rates for endogenously expressed repressor complexes. We found that
      unlike hydroxamate type inhibitors, aminobenzamides exhibited slow binding
      kinetics dependent on association within protein complexes. These findings were
      in agreement with a delayed cellular response on acetylation levels of distinct
      histone sites and the inability of aminobenzamides to inhibit HDAC activity of a
      Sin3 complex isolated from K562 cells. 

PMID- 24877717
TI  - A Fraxinus excelsior L. seeds/fruits extract benefits glucose homeostasis and
      adiposity related markers in elderly overweight/obese subjects: a longitudinal,
      randomized, crossover, double-blind, placebo-controlled nutritional intervention
      study.
AB  - PURPOSE: The aim of this study was to investigate the potential benefits of an
      extract obtained from seeds/fruits of an Oleaceae (Fraxinus excelsior L.) on
      glucose homeostasis and associated metabolic markers in non-diabetic
      overweight/obese subjects. MATERIALS AND METHODS: This study was performed in 22
      participants (50-80 years-old; BMI 31.0 kg/m(2)). The design was a longitudinal,
      randomized, crossover, double-blind, placebo-controlled 7-week nutritional
      intervention. The participants received daily 3 capsules each containing either
      333 mg of an extract from Fraxinus excelsior L. seeds (Glucevia((r))) or placebo
      capsules (control) in a random order for 3 weeks with 1 week of washout between
      treatments. Moreover, they followed a balanced covert energy-restricted diet (
      15% energy). All variables were measured at the beginning and at the end of each
      period. RESULTS: Compared to baseline, the administration of 1 g of Glucevia((r))
      for 3 weeks resulted in significantly lower incremental glucose area under the
      curve (-28.2%; p<0.01), and significantly lower 2 h blood glucose values (-14%;
      p<0.01) following an oral glucose tolerance test. No significant changes were
      found in the control group (-7.9% AUC, -1.6% 2h blood glucose). Furthermore,
      significant differences were found between responses in the control and
      Glucevia((r)) groups with respect to serum fructosamine and plasma glucagon
      levels (p<0.01 and p<0.05, respectively). Interestingly, administration of
      Glucevia((r)) significantly increased the adiponectin:leptin ratio (p<0.05) and
      decreased fat mass (p<0.01) compared to control (p<0.05). CONCLUSION: The
      administration of an extract from Fraxinus excelsior L. seeds/fruits in
      combination with a moderate hypocaloric diet may be beneficial in metabolic
      disturbances linked to impaired glucose tolerance, obesity, insulin resistance
      and inflammatory status, specifically in older adults.

PMID- 24877720
TI  - Dislocation of a total hip arthroplasty: acute management in the ED.
AB  - Dislocation is one of the most common complications of total hip arthroplasty
      (THA). Because of the growing number of patients undergoing THA annually and the
      immense number of patients who have previously undergone the procedure,
      familiarity with the diagnosis and treatment of this complication is critical.
      Although the most common direction of dislocation is posterior, anterior
      dislocations do occur, and correctly identifying the direction of dislocation is
      important before attempted closed reduction as both the reduction maneuvers used
      and the postoperative instructions afterward are distinct for an anterior as
      opposed to a posterior dislocation. We present the current case of an anterior
      hip dislocation that was unable to be closed reduced as the direction of
      dislocation was presumed to be posterior. Although a shoot through lateral is
      recommended in all cases to confirm the direction of dislocation, we highlight
      how the physician can differentiate the direction of dislocation based on the
      position of the foot and location of the lesser trochanter on the anteroposterior
      radiograph.

PMID- 24877721
TI  - Resistance of Escherichia coli urinary isolates in ED-treated patients from a
      community hospital.
AB  - PURPOSE: The purpose of this study is to provide resistance data for Escherichia
      coli isolates causing urinary tract infections in emergency department (ED)
      patients not requiring admission and explore if differences between this
      subpopulation and the hospital antibiogram exist. Differences between community
      acquired urinary tract infection (CA-UTI) and health care-associated (HA-UTI)
      subgroups were also investigated. METHODS: Patients with a positive urine culture
      treated and discharged from the ED of a 200-bed community hospital were reviewed.
      Patients with urinary isolates of more than 100000 colony-forming unit/mL and
      documented intention to treat were included. Patients who required admission,
      were pregnant, less than the age of 18 years, or who had a positive culture but
      without any evidence of intention to treat were excluded. Only the initial visit
      was included for patients who returned to the ED within 7 days. RESULTS: Overall,
      308 visits were screened, and 217 were included. Of these, 78.3% were CA-UTI, and
      21.7% were HA-UTI. Females comprised 88.5% of all patients. E coli was the most
      common pathogen overall and in both subgroups. E coli resistance to levofloxacin
      was 13.5% overall, 9.2% for CA-UTI, and 38.5% for HA-UTI compared with 27% on the
      hospital antibiogram. E coli resistance to sulfamethoxazole/trimethoprim was
      26.9% overall, 25.2% for CA-UTI, and 34.6% for HA-UTI vs 26% on the antibiogram.
      CONCLUSIONS: E coli susceptibility for ED patients not requiring admission may
      not be accurately represented by hospital antibiograms that contain culture data
      from various patient types, sites of infection, or patients with varying illness
      severity. Separation of the ED population into CA-UTI and HA-UTI subgroups may be
      helpful when selecting empiric antibiotic therapy.

PMID- 24877723
TI  - Changes of murine sperm phospholipid composition during epididymal maturation
      determined by MALDI-TOF mass spectrometry.
AB  - After leaving the testis, spermatozoa undergo several important steps of
      biochemical maturation during the passage through the epididymis, increasing
      their motility and fertilizing ability. These changes comprise (among others) the
      modification of the phospholipid composition of the sperm membrane. This process
      is thought to be important for the achievement of motility and fertilizing
      capacity. The lipids of the sperm membrane are characterized by a significant
      content of unsaturated fatty acyl residues, resulting in a high sensitivity
      against oxidative stress. This is evidenced by the appearance of lysolipids, for
      example, lysophosphatidylcholine, which acts like a detergent and is normally
      present in only very small amounts in biological membranes. The epididymis
      represents a tubular system comprising three main parts (caput, corpus, and
      cauda), through which the spermatozoa are consecutively transported undergoing
      distinct maturation stages. Using matrix-assisted laser desorption/ionization
      time-of-flight mass spectrometry, we established three striking differences in
      the lipid composition of murine spermatozoa from the different epididymal
      regions: in comparison to the caput sperm, sperm from the cauda are characterized
      by (1) a higher degree of unsaturation (PC 18:0/22:5 and 18:0/22:6 vs. 18:0/20:4
      and 18:0/18:1), (2) an enhanced plasmalogen content, and (3) an enhanced content
      of lysolipids. These changes are likely to be of physiological relevance and
      potentially useful as diagnostic markers of sperm maturation and acquisition of
      motility.

PMID- 24877722
TI  - Effects of indole-3-carbinol on clonidine-induced neurotoxicity in rats: Impact
      on oxidative stress, inflammation, apoptosis and monoamine levels.
AB  - The relationship between inflammation, oxidative stress and the incidence of
      depression had been well studied. Indole-3-carbinol (I3C), a natural active
      compound found in cruciferous vegetables, was shown to have anti-oxidant and anti
      inflammatory activities. Therefore, the aim of this study was to investigate the
      potential protective effects of I3C against clonidine-induced depression-like
      behaviors in rats. Also, the possible mechanisms underlying this neuroprotection;
      anti-oxidant, anti-inflammatory as well as the modulatory effect on monoamine
      levels in brain tissues were investigated. I3C was given orally (50mg/kg) daily
      over 2 weeks starting 7 days before giving clonidine (0.8mg/kg i.p.). Fluoxetine
      was used as a standard anti-depressant. Open-field test and forced swimming test
      were carried out to assess exploratory activity and despair behavior,
      respectively. I3C showed a significant improvement in the behavioral changes
      induced by clonidine. As indicators of oxidative stress, clonidine induced a
      significant reduction in GSH and SOD levels as well as an increase lipid
      peroxidation level. Tissue levels of pro-inflammatory and apoptotic markers were
      significantly increased in clonidine group. In addition, monoamine levels;
      noradrenaline and serotonin, showed a drastic decrease in clonidine group. Also,
      neuron specific enolase (NSE) was significantly elevated in clonidine group. In
      contrast, I3C pre-treatment significantly attenuated clonidine-induced oxidative
      stress, inflammation, apoptosis, decreased NSE expression and increased levels of
      monoamines. Fluoxetine was used as a standard. In conclusion, the findings of
      this study suggest that I3C protects against clonidine-induced depression. This
      neuroprotective effect is partially mediated by its anti-oxidant, anti
      inflammatory and anti-apoptotic activities as well as elevating monoamines
      levels. 

PMID- 24877724
TI  - Monitoring preantral follicle survival and growth in bovine ovarian biopsies by
      repeated use of neutral red and cultured in vitro under low and high oxygen
      tension.
AB  - The development and optimization of preantral follicle culture methods are
      crucial in fertility preservation strategies. As preantral follicle dynamics are
      usually assessed by various invasive techniques, the need for alternative
      noninvasive evaluation tools exists. Recently, neutral red (NR) was put forward
      to visualize preantral follicles in situ within ovarian cortical fragments.
      However, intense light exposure of NR-stained tissues can lead to cell death
      because of increased reactive oxygen species production, which is also associated
      with elevated oxygen tension. Therefore, we hypothesize that after repeated NR
      staining, follicle viability and dynamics can be altered by changes in oxygen
      tension. In the present study, we aim (1) to determine whether NR can be used to
      repeatedly assess follicular growth, activation, and viability and (2) to assess
      the effect of a low (5% O2) or high (20% O2) oxygen tension on the viability,
      growth, and stage transition of preantral follicles cultured in vitro by means of
      repeated NR staining. Cortical slices (n = 132; six replicates) from bovine
      ovaries were incubated for 3 hours at 37  degrees C in a Leibovitz medium with 50
      MUg/mL NR. NR-stained follicles were evaluated in situ for follicle diameter and
      morphology. Next, cortical fragments were individually cultured in McCoy's 5A
      medium for 6 days at 37  degrees C, 5% CO2, and 5% or 20% O2. On Days 4 and 6,
      the fragments were restained by adding NR to the McCoy's medium and follicles
      were reassessed. In both low and high oxygen tension treatment groups,
      approximately 70% of the initial follicles survived a 6-day in vitro culture, but
      no significant difference in follicle survival on Day 4 or 6 could be observed
      compared with Day 0 (P > 0.05). A significant decrease in the number of
      primordial and increase in primary and secondary follicles was observed within 4
      days of culture (P < 0.001). In addition, a significant increase of the mean
      follicle diameter in NR-stained follicles was observed (P < 0.001), resulting in
      an average growth of 11.82 +/- 0.81 MUm (5% O2) and 11.78 +/- 1.06 MUm (20% O2)
      on Day 4 and 20.94 +/- 1.24 MUm (5% O2) and 19.12 +/- 1.36 MUm (20% O2) on Day 6
      compared with Day 0. No significant differences in follicle growth rate or stage
      transition could be observed between 5% and 20% O2 (P > 0.05). In conclusion,
      after repeated NR staining, we could not find a difference between low and high
      oxygen tension in terms of follicle viability, stage transition, or growth.
      Therefore, under our culture conditions follicle dynamics are not determined by
      the oxygen tension in combination with quality assessment protocols using
      repeated NR staining.

PMID- 24877728
TI  - Incremental learning by message passing in hierarchical temporal memory.
AB  - Hierarchical temporal memory (HTM) is a biologically inspired framework that can
      be used to learn invariant representations of patterns in a wide range of
      applications. Classical HTM learning is mainly unsupervised, and once training is
      completed, the network structure is frozen, thus making further training (i.e.,
      incremental learning) quite critical. In this letter, we develop a novel
      technique for HTM (incremental) supervised learning based on gradient descent
      error minimization. We prove that error backpropagation can be naturally and
      elegantly implemented through native HTM message passing based on belief
      propagation. Our experimental results demonstrate that a two-stage training
      approach composed of unsupervised pretraining and supervised refinement is very
      effective (both accurate and efficient). This is in line with recent findings on
      other deep architectures. 

PMID- 24877726
TI  - Genome-wide analysis of the regulatory function mediated by the small regulatory
      psm-mec RNA of methicillin-resistant Staphylococcus aureus.
AB  - Several methicillin resistance (SCCmec) clusters characteristic of hospital
      associated methicillin-resistant Staphylococcus aureus (MRSA) strains harbor the
      psm-mec locus. In addition to encoding the cytolysin, phenol-soluble modulin
      (PSM)-mec, this locus has been attributed gene regulatory functions. Here we
      employed genome-wide transcriptional profiling to define the regulatory function
      of the psm-mec locus. The immune evasion factor protein A emerged as the primary
      conserved and strongly regulated target of psm-mec, an effect we show is mediated
      by the psm-mec RNA. Furthermore, the psm-mec locus exerted regulatory effects
      that were more moderate in extent. For example, expression of PSM-mec limited
      expression of mecA, thereby decreasing methicillin resistance. Our study shows
      that the psm-mec locus has a rare dual regulatory RNA and encoded cytolysin
      function. Furthermore, our findings reveal a specific mechanism underscoring the
      recently emerging concept that S. aureus strains balance pronounced virulence and
      high expression of antibiotic resistance. 

PMID- 24877727
TI  - MALDI-TOF MS and chemometric based identification of the Acinetobacter
      calcoaceticus-Acinetobacter baumannii complex species.
AB  - MALDI-TOF MS is becoming the technique of choice for rapid bacterial
      identification at species level in routine diagnostics. However, some drawbacks
      concerning the identification of closely related species such as those belonging
      to the Acinetobacter calcoaceticus-Acinetobacter baumannii (Acb) complex lead to
      high rates of misidentifications. In this work we successfully developed an
      approach that combines MALDI-TOF MS and chemometric tools to discriminate the six
      Acb complex species (A. baumannii, Acinetobacter nosocomialis, Acinetobacter
      pittii, A. calcoaceticus, genomic species "Close to 13TU" and genomic species
      "Between 1 and 3"). Mass spectra of 83 taxonomically well characterized clinical
      strains, reflecting the breadth of currently known phenetic diversity within the
      Acb complex, were achieved from intact cells and cell extracts and analyzed with
      hierarchical cluster analysis (HCA) and partial least squares discriminant
      analysis (PLSDA). This combined approach lead to 100% of correct species
      identification using mass spectra obtained from intact cells. Moreover, it was
      possible to discriminate two Acb complex species (genomic species "Close to 13TU"
      and genomic species "Between 1 and 3") not included in the MALDI Biotyper
      database. 

PMID- 24877729
TI  - How to compress sequential memory patterns into periodic oscillations: general
      reduction rules.
AB  - A neural network with symmetric reciprocal connections always admits a Lyapunov
      function, whose minima correspond to the memory states stored in the network.
      Networks with suitable asymmetric connections can store and retrieve a sequence
      of memory patterns, but the dynamics of these networks cannot be characterized as
      readily as that of the symmetric networks due to the lack of established general
      methods. Here, a reduction method is developed for a class of asymmetric
      attractor networks that store sequences of activity patterns as associative
      memories, as in a Hopfield network. The method projects the original activity
      pattern of the network to a low-dimensional space such that sequential memory
      retrievals in the original network correspond to periodic oscillations in the
      reduced system. The reduced system is self-contained and provides quantitative
      information about the stability and speed of sequential memory retrieval in the
      original network. The time evolution of the overlaps between the network state
      and the stored memory patterns can also be determined from extended reduced
      systems. The reduction procedure can be summarized by a few reduction rules,
      which are applied to several network models, including coupled networks and
      networks with time-delayed connections, and the analytical solutions of the
      reduced systems are confirmed by numerical simulations of the original networks.
      Finally, a local learning rule that provides an approximation to the connection
      weights involving the pseudoinverse is also presented. 

PMID- 24877730
TI  - Bayesian active learning of neural firing rate maps with transformed gaussian
      process priors.
AB  - A firing rate map, also known as a tuning curve, describes the nonlinear
      relationship between a neuron's spike rate and a low-dimensional stimulus (e.g.,
      orientation, head direction, contrast, color). Here we investigate Bayesian
      active learning methods for estimating firing rate maps in closed-loop
      neurophysiology experiments. These methods can accelerate the characterization of
      such maps through the intelligent, adaptive selection of stimuli. Specifically,
      we explore the manner in which the prior and utility function used in Bayesian
      active learning affect stimulus selection and performance. Our approach relies on
      a flexible model that involves a nonlinearly transformed gaussian process (GP)
      prior over maps and conditionally Poisson spiking. We show that infomax learning,
      which selects stimuli to maximize the information gain about the firing rate map,
      exhibits strong dependence on the seemingly innocuous choice of nonlinear
      transformation function. We derive an alternate utility function that selects
      stimuli to minimize the average posterior variance of the firing rate map and
      analyze the surprising relationship between prior parameterization, stimulus
      selection, and active learning performance in GP-Poisson models. We apply these
      methods to color tuning measurements of neurons in macaque primary visual cortex.

PMID- 24877731
TI  - ROC-based estimates of neural-behavioral covariations using matched filters.
AB  - Correlations between responses in visual cortex and perceptual performance help
      draw a functional link between neural activity and visually guided behavior.
      These correlations are commonly derived with ROC-based neural-behavioral
      covariances (referred to as choice or detect probability) using boxcar analysis
      windows. Although boxcar windows capture the covariation between neural activity
      and behavior during steady-state stimulus presentations, they are not optimized
      to capture these correlations during short time-varying visual inputs. In this
      study, we implemented a matched-filter technique, combined with cross-validation,
      to improve the estimation of ROC-based neural-behavioral covariance under short
      and dynamic stimulus conditions. We show that this approach maximizes the area
      under the ROC curve and converges to the true neural-behavioral covariance using
      a Poisson spiking model. We also demonstrate that the matched filter, combined
      with cross-validation, reveals the dynamics of the neural-behavioral covariations
      of individual MT neurons during the detection of a brief motion stimulus. 

PMID- 24877732
TI  - Anatomical constraints on lateral competition in columnar cortical architectures.
AB  - Competition is a well-studied and powerful mechanism for information processing
      in neuronal networks, providing noise rejection, signal restoration, decision
      making and associative memory properties, with relatively simple requirements for
      network architecture. Models based on competitive interactions have been used to
      describe the shaping of functional properties in visual cortex, as well as the
      development of functional maps in columnar cortex. These models require
      competition within a cortical area to occur on a wider spatial scale than
      cooperation, usually implemented by lateral inhibitory connections having a
      longer range than local excitatory connections. However, measurements of cortical
      anatomy reveal that the spatial extent of inhibition is in fact more restricted
      than that of excitation. Relatively few models reflect this, and it is unknown
      whether lateral competition can occur in cortical-like networks that have a
      realistic spatial relationship between excitation and inhibition. Here we analyze
      simple models for cortical columns and perform simulations of larger models to
      show how the spatial scales of excitation and inhibition can interact to produce
      competition through disynaptic inhibition. Our findings give strong support to
      the direct coupling effect-that the presence of competition across the cortical
      surface is predicted well by the anatomy of direct excitatory and inhibitory
      coupling and that multisynaptic network effects are negligible. This implies that
      for networks with short-range inhibition and longer-range excitation, the spatial
      extent of competition is even narrower than the range of inhibitory connections.
      Our results suggest the presence of network mechanisms that focus on intra-rather
      than intercolumn competition in neocortex, highlighting the need for both new
      models and direct experimental characterizations of lateral inhibition and
      competition in columnar cortex. 

PMID- 24877733
TI  - Information-theoretic semi-supervised metric learning via entropy regularization.
AB  - We propose a general information-theoretic approach to semi-supervised metric
      learning called SERAPH (SEmi-supervised metRic leArning Paradigm with
      Hypersparsity) that does not rely on the manifold assumption. Given the
      probability parameterized by a Mahalanobis distance, we maximize its entropy on
      labeled data and minimize its entropy on unlabeled data following entropy
      regularization. For metric learning, entropy regularization improves manifold
      regularization by considering the dissimilarity information of unlabeled data in
      the unsupervised part, and hence it allows the supervised and unsupervised parts
      to be integrated in a natural and meaningful way. Moreover, we regularize SERAPH
      by trace-norm regularization to encourage low-dimensional projections associated
      with the distance metric. The nonconvex optimization problem of SERAPH could be
      solved efficiently and stably by either a gradient projection algorithm or an EM
      like iterative algorithm whose M-step is convex. Experiments demonstrate that
      SERAPH compares favorably with many well-known metric learning methods, and the
      learned Mahalanobis distance possesses high discriminability even under noisy
      environments. 

PMID- 24877734
TI  - Tonically balancing intracortical excitation and inhibition by GABAergic
      gliotransmission.
AB  - For sensory cortices to respond reliably to feature stimuli, the balancing of
      neuronal excitation and inhibition is crucial. A typical example might be the
      balancing of phasic excitation within cell assemblies and phasic inhibition
      between cell assemblies. The former controls the gain of and the latter the
      tuning of neuronal responses. A change in ambient GABA concentration might affect
      the dynamic behavior of neurons in a tonic manner. For instance, an increase in
      ambient GABA concentration enhances the activation of extrasynaptic receptors,
      augments an inhibitory current, and thus inhibits neurons. When a decrease in
      ambient GABA concentration occurs, the tonic inhibitory current is reduced, and
      thus the neurons are relatively excited. We simulated a neural network model in
      order to examine whether and how such a tonic excitatory-inhibitory mechanism
      could work for sensory information processing. The network consists of cell
      assemblies. Each cell assembly, comprising principal cells (P), GABAergic
      interneurons (Ia, Ib), and glial cells (glia), responds to one particular feature
      stimulus. GABA transporters, embedded in glial plasma membranes, regulate ambient
      GABA levels. Hypothetical neuron-glia signaling via inhibitory (Ia-to-glia) and
      excitatory (P-to-glia) synaptic contacts was assumed. The former let transporters
      import (remove) GABA from the extracellular space and excited stimulus-relevant P
      cells. The latter let them export GABA into the extracellular space and inhibited
      stimulus-irrelevant P cells. The main finding was that the glial membrane
      transporter gave a combinatorial excitatory-inhibitory effect on P cells in a
      tonic manner, thereby improving the gain and tuning of neuronal responses.
      Interestingly, it worked cooperatively with the conventional, phasic excitatory
      inhibitory mechanism. We suggest that the GABAergic gliotransmission mechanism
      may provide balanced intracortical excitation and inhibition so that the best
      perceptual performance of the cortex can be achieved. 

PMID- 24877735
TI  - The competing benefits of noise and heterogeneity in neural coding.
AB  - Noise and heterogeneity are both known to benefit neural coding. Stochastic
      resonance describes how noise, in the form of random fluctuations in a neuron's
      membrane voltage, can improve neural representations of an input signal. Neuronal
      heterogeneity refers to variation in any one of a number of neuron parameters and
      is also known to increase the information content of a population. We explore the
      interaction between noise and heterogeneity and find that their benefits to
      neural coding are not independent. Specifically, a neuronal population better
      represents an input signal when either noise or heterogeneity is added, but
      adding both does not always improve representation further. To explain this
      phenomenon, we propose that noise and heterogeneity operate using two shared
      mechanisms: (1) temporally desynchronizing the firing of neurons in the
      population and (2) linearizing the response of a population to a stimulus. We
      first characterize the effects of noise and heterogeneity on the information
      content of populations of either leaky integrate-and-fire or FitzHugh-Nagumo
      neurons. We then examine how the mechanisms of desynchronization and
      linearization produce these effects, and find that they work to distribute
      information equally across all neurons in the population in terms of both signal
      timing (desynchronization) and signal amplitude (linearization). Without noise or
      heterogeneity, all neurons encode the same aspects of the input signal; adding
      noise or heterogeneity allows neurons to encode complementary aspects of the
      input signal, thereby increasing information content. The simulations detailed in
      this letter highlight the importance of heterogeneity and noise in population
      coding, demonstrate their complex interactions in terms of the information
      content of neurons, and explain these effects in terms of underlying mechanisms. 

PMID- 24877736
TI  - A bayesian model of polychronicity.
AB  - A significant feature of spiking neural networks with varying connection delays,
      such as those in the brain, is the existence of strongly connected groups of
      neurons known as polychronous neural groups (PNGs). Polychronous groups are found
      in large numbers in these networks and are proposed by Izhikevich (2006a) to
      provide a neural basis for representation and memory. When exposed to a familiar
      stimulus, spiking neural networks produce consistencies in the spiking output
      data that are the hallmarks of PNG activation. Previous methods for studying the
      PNG activation response to stimuli have been limited by the template-based
      methods used to identify PNG activation. In this letter, we outline a new method
      that overcomes these difficulties by establishing for the first time a
      probabilistic interpretation of PNG activation. We then demonstrate the use of
      this method by investigating the claim that PNGs might provide the foundation of
      a representational system.

PMID- 24877737
TI  - Sequential activity in asymmetrically coupled winner-take-all circuits.
AB  - Understanding the sequence generation and learning mechanisms used by recurrent
      neural networks in the nervous system is an important problem that has been
      studied extensively. However, most of the models proposed in the literature are
      either not compatible with neuroanatomy and neurophysiology experimental
      findings, or are not robust to noise and rely on fine tuning of the parameters.
      In this work, we propose a novel model of sequence learning and generation that
      is based on the interactions among multiple asymmetrically coupled winner-take
      all (WTA) circuits. The network architecture is consistent with mammalian
      cortical connectivity data and uses realistic neuronal and synaptic dynamics that
      give rise to noise-robust patterns of sequential activity. The novel aspect of
      the network we propose lies in its ability to produce robust patterns of
      sequential activity that can be halted, resumed, and readily modulated by
      external input, and in its ability to make use of realistic plastic synapses to
      learn and reproduce the arbitrary input-imposed sequential patterns. Sequential
      activity takes the form of a single activity bump that stably propagates through
      multiple WTA circuits along one of a number of possible paths. Because the
      network can be configured to either generate spontaneous sequences or wait for
      external inputs to trigger a transition in the sequence, it provides the basis
      for creating state-dependent perception-action loops. We first analyze a rate
      based approximation of the proposed spiking network to highlight the relevant
      features of the network dynamics and then show numerical simulation results with
      spiking neurons, realistic conductance-based synapses, and spike-timing dependent
      plasticity (STDP) rules to validate the rate-based model. 

PMID- 24877738
TI  - Memory nearly on a spring: a mean first passage time approach to memory
      lifetimes.
AB  - We study memory lifetimes in a perceptron-based framework with binary synapses,
      using the mean first passage time for the perceptron's total input to fall below
      firing threshold to define memory lifetimes. Working with the simplest memory
      related model of synaptic plasticity, we may obtain exact results for memory
      lifetimes or, working in the continuum limit, good analytical approximations that
      afford either much qualitative insight or extremely good quantitative agreement.
      In one particular limit, we find that memory dynamics reduce to the well
      understood Ornstein-Uhlenbeck process. We show that asymptotically, the lifetimes
      of memories grow logarithmically in the number of synapses when the perceptron's
      firing threshold is zero, reproducing standard results from signal-to-noise ratio
      analyses. However, this is only an asymptotically valid result, and we show that
      extending its application outside the range of its validity leads to a massive
      overestimate of the minimum number of synapses required for successful memory
      encoding. In the case that the perceptron's firing threshold is positive, we find
      the remarkable result that memory lifetimes are strictly bounded from above.
      Asymptotically, the dependence of memory lifetimes on the number of synapses
      drops out entirely, and this asymptotic result provides a strict upper bound on
      memory lifetimes away from this asymptotic regime. The classic logarithmic growth
      of memory lifetimes in the simplest, palimpsest memories is therefore untypical
      and nongeneric: memory lifetimes are typically strictly bounded from above. 

PMID- 24877739
TI  - Model-driven engineering of gene expression from RNA replicons.
AB  - RNA replicons are an emerging platform for engineering synthetic biological
      systems. Replicons self-amplify, can provide persistent high-level expression of
      proteins even from a small initial dose, and, unlike DNA vectors, pose minimal
      risk of chromosomal integration. However, no quantitative model sufficient for
      engineering levels of protein expression from such replicon systems currently
      exists. Here, we aim to enable the engineering of multigene expression from more
      than one species of replicon by creating a computational model based on our
      experimental observations of the expression dynamics in single- and multireplicon
      systems. To this end, we studied fluorescent protein expression in baby hamster
      kidney (BHK-21) cells using a replicon derived from Sindbis virus (SINV). We
      characterized expression dynamics for this platform based on the dose-response of
      a single species of replicon over 50 h and on a titration of two cotransfected
      replicons expressing different fluorescent proteins. From this data, we derive a
      quantitative model of multireplicon expression and validate it by designing a
      variety of three-replicon systems, with profiles that match desired expression
      levels. We achieved a mean error of 1.7-fold on a 1000-fold range, thus
      demonstrating how our model can be applied to precisely control expression levels
      of each Sindbis replicon species in a system. 

PMID- 24877740
TI  - Hypoxia induced changes in expression of proteins involved in iron uptake and
      storage in cultured lens epithelial cells.
AB  - Hypoxia inducible factor (HIF) regulates expression of over 60 genes by binding
      to hypoxia response elements (HRE) located upstream of the transcriptional start
      sites. Many genes encoding proteins involved in iron transport and homeostasis
      are regulated by HIF. Expression of iron handling proteins can also be
      translationally regulated by binding of iron regulatory protein (IRP) to iron
      responsive elements (IREs) on the mRNA of ferritin chains and transferrin
      receptor (TfR). Lens epithelial cells (LEC) function in a low oxygen environment.
      This increases the risk of iron catalyzed formation of reactive oxygen species
      (ROS) and oxidative cell damage. We examined changes in expression of ferritin
      (iron storage protein) and Tf/TfR1 (iron uptake proteins) in LEC cultured under
      hypoxic conditions. Ferritin consists of 24 subunits of two types, heavy (H
      chain) and light (L-chain) assembled in a cell specific ratio. Real-time PCR
      showed that 24 h exposure to hypoxia lowered transcription of both ferritin
      chains by over 50% when compared with normoxic LEC. However it increased the
      level of ferritin chain proteins (20% average). We previously found that 6 h
      exposure of LEC to hypoxia increased the concentration of cytosolic iron which
      would stimulate translation of ferritin chains. This elevated ferritin
      concentration increased the iron storage capacity of LEC. Hypoxic LEC labeled
      with 59FeTf incorporated 70% more iron into ferritin after 6 h as compared to
      normoxic LEC. Exposure of LEC to hypoxia for 24 h reduced the concentration of
      TfR1 in cell lysates. As a result, hypoxic LEC internalized less Tf at this later
      time point. Incorporation of 59Fe into ferritin of hypoxic LEC after 24 h did not
      differ from that of normoxic LEC due to lower 59FeTf uptake. This study showed
      that hypoxia acutely increased iron storage capacity and lowered iron uptake due
      to changes in expression of iron handling proteins. These changes may better
      protect LEC against oxidative stress by limiting iron-catalyzed ROS formation in
      the low oxygen environment in which the lens resides.

PMID- 24877741
TI  - Massive formation of square array junctions dramatically alters cell shape but
      does not cause lens opacity in the cav1-KO mice.
AB  - The wavy square array junctions are composed of truncated aquaporin-0 (AQP0)
      proteins typically distributed in the deep cortical and nuclear fibers in wild
      type lenses. These junctions may help maintain the narrowed extracellular spaces
      between fiber cells to minimize light scattering. Herein, we investigate the
      impact of the cell shape changes, due to abnormal formation of extensive square
      array junctions, on the lens opacification in the caveolin-1 knockout mice. The
      cav1-KO and wild-type mice at age 1-22 months were used. By light microscopy
      examinations, cav1-KO lenses at age 1-18 months were transparent in both cortical
      and nuclear regions, whereas some lenses older than 18 months old exhibited
      nuclear cataracts. Scanning EM consistently observed the massive formation of
      ridge-and-valley membrane surfaces in young fibers at approximately 150 MUm deep
      in all cav1-KO lenses studied. In contrast, the typical ridge-and-valleys were
      only seen in mature fibers deeper than 400 MUm in wild-type lenses. The resulting
      extensive ridge-and-valleys dramatically altered the overall cell shape in cav1
      KO lenses. Remarkably, despite dramatic shape changes, these deformed fiber cells
      remained intact and made close contact with their neighboring cells. By freeze
      fracture TEM, ridge-and-valleys exhibited the typical orthogonal arrangement of
      6.6 nm square array intramembrane particles and displayed the narrowed
      extracellular spaces. Immunofluorescence analysis showed that AQP0 C-terminus
      labeling was significantly decreased in outer cortical fibers in cav1-KO lenses.
      However, freeze-fracture immunogold labeling showed that the AQP0 C-terminus
      antibody was sparsely distributed on the wavy square array junctions, suggesting
      that the cleavage of AQP0 C-termini might not yet be complete. The cav1-KO lenses
      with nuclear cataracts showed complete cellular breakdown and large globule
      formation in the lens nucleus. This study suggests that despite dramatic cell
      shape changes, the massive formation of wavy square array junctions in intact
      fibers may provide additional adhesive support for maintaining the narrowed
      extracellular spaces that are crucial for the transparency of cav1-KO lenses. 

PMID- 24877742
TI  - Neuroprotection by rat Muller glia against high glucose-induced neurodegeneration
      through a mechanism involving ERK1/2 activation.
AB  - Muller cell activation is an early finding in diabetic retinopathy (DR), but its
      physiopathologic role in the disease is still unclear, especially in the early
      phases. We investigated on Muller glial activation in primary rat retinal
      cultures, exposed to High Glucose (HG), and in retinas from streptozotocin (stz)
      induced diabetic rats. First of all, we checked if the presence of Muller glia
      influenced HG neurotoxicity. In mixed glial/neuronal retinal cultures, a single
      HG administration (sHG) for 48 h induced activation of Muller glia, in absence of
      neuronal damage. In contrast, in pure neuronal cultures, a marked neurotoxic
      effect was detected, suggesting that in this cell model Muller glia protect
      neurons from HG neurotoxicity. To better mimic the diabetic milieu, where retinal
      cells are constantly bathed in hyperglycemic fluid, and to further characterize
      astrocytic neuroprotective ability, mixed retinal cultures were exposed to
      repeated daily replacement of HG (rHG). In this paradigm, starting from 48 h,
      increased apoptosis and synaptic loss were observed, even in the presence of
      Muller cells. Phosphorylation of extracellular signal-regulated kinase 1/2
      (ERK1/2), whose activation triggers a prosurvival pathway, was increased by sHG,
      while it was down-regulated by rHG, suggesting that ERK1/2 activation is involved
      in neuroprotection. Consistently, in presence of ERK1/2 inhibitor PD98059, sHG
      exerted a proapoptotic effect also in glial/neuronal retinal cultures. In line
      with the in vitro data, early changes in diabetic retinas from stz-injected rats
      included Muller cell activation and increased pERK1/2 levels, but no signs of
      neuronal damage. These results suggest that, in the early phases of DR, Muller
      glial activation does not contribute to neurodegeneration, but may indeed have a
      neuroprotective activity against HG-induced neurotoxicity through a mechanism
      involving pERK1/2. 

PMID- 24877743
TI  - Acute renal failure and metformin-associated lactic acidosis following
      colonoscopy.
AB  - Two patients with type 2 DM developed acute kidney injury and lactic acidosis
      following colonoscopy despite withholding metformin. We recommend that DM
      patients on metformin also withhold ACEI, ARB until their dehydration is reversed
      after colonoscopy. This should reduce the risk of acute renal failure (ARF) and
      of lactic acidosis. 

PMID- 24877744
TI  - Genetic and biochemical evidence that recombinant Enterococcus spp. strains
      expressing gelatinase (GelE) produce bovine milk-derived hydrolysates with high
      angiotensin converting enzyme-inhibitory activity (ACE-IA).
AB  - In this work, genes encoding gelatinase (gelE) and serine proteinase (sprE), two
      extracellular proteases produced by Enterococcus faecalis DBH18, were cloned in
      the protein expression vector pMG36c, containing the constitutive P32 promoter,
      generating the recombinant plasmids pCG, pCSP, and pCGSP encoding gelE, sprE, and
      gelE-sprE, respectively. Transformation of noncaseinolytic E. faecalis P36, E.
      faecalis JH2-2, E. faecium AR24, and E. hirae AR14 strains with these plasmids
      permitted detection of caseinolytic activity only in the strains transformed with
      pCG or pCGSP. Complementation of a deletion (knockout) mutant of E. faecalis V583
      for production of gelatinase (GelE) with pCG unequivocally supported that gelE is
      responsible for the caseinolytic activity of the transformed strain grown in
      bovine skim milk (BSM). RP-HPLC-MS/MS analysis of hydrolysates of transformed
      Enterococcus spp. strains grown in BSM permitted the identification of 38 major
      peptide fragments including peptides with previously reported angiotensin
      converting enzyme-inhibitory activity (ACE-IA), antihypertensive activity, and
      antioxidant activity. 

PMID- 24877751
TI  - Motion of the shoulder complex in individuals with isolated acromioclavicular
      osteoarthritis and associated with rotator cuff dysfunction: part 1 - Three
      dimensional shoulder kinematics.
AB  - This study described the three-dimensional shoulder motion during the arm
      elevation in individuals with isolated acromioclavicular osteoarthritis (ACO) and
      ACO associated with rotator cuff disease (RCD), as compared to controls. Seventy
      four participants (ACO=23, ACO+RCD=25, Controls=26) took part of this study.
      Disability was assessed with the DASH, three-dimensional kinematics were
      collected during arm elevation in the sagittal and scapular planes, and pain was
      assessed with the 11-point numeric pain rating scale. For each kinematic variable
      and demographic variables, separate linear mixed-model 2-way ANOVAs were
      performed to compare groups. Both ACO groups had higher DASH and pain scores. At
      the scapulothoracic joint, the isolated ACO group had greater internal rotation
      than control, and the ACO+RCD group had greater upward rotation than both other
      groups. At the sternoclavicular joint, both groups with ACO had less retraction,
      and the isolated ACO group had less elevation and posterior rotation. At the
      acromioclavicular joint, the isolated ACO group had greater upward rotation, and
      both ACO groups had greater posterior tilting. Patients with ACO had altered
      shoulder kinematics, which may represent compensatory responses to reduce pain
      and facilitate arm motion during arm elevation and lowering. 

PMID- 24877745
TI  - Outcomes and cost benefits of functional endoscopic sinus surgery in severely
      asthmatic patients with chronic rhinosinusitis.
AB  - OBJECTIVES: To evaluate the outcomes (using validated outcome tools) and cost
      benefits of functional endoscopic sinus surgery in a population of severely
      asthmatic patients with chronic rhinosinusitis. METHODS: A prospective cohort
      study was conducted. The study comprised consecutive patients diagnosed with
      asthma and chronic rhinosinusitis for whom medical treatment had failed and who
      were scheduled for functional endoscopic sinus surgery. General health and
      disease-specific outcome questionnaires were completed pre- and post-operatively.
      Costs associated with both functional endoscopic sinus surgery and out-patient
      visits to a comprehensive asthma clinic were calculated. RESULTS: A total of 47
      patients completed the surveys. The average improvement in Chronic Sinusitis
      Survey scores following functional endoscopic sinus surgery was 17 per cent. The
      average reduction in out-patient asthma clinic visits was 50 per cent, which
      translates to an average cost saving of $1035 Canadian dollars per patient per
      year. CONCLUSION: Functional endoscopic sinus surgery is a cost-effective
      treatment modality for asthmatic patients with chronic rhinosinusitis. This
      information is important for: the distribution and planning of resources,
      prioritising health programmes, and establishing practice guidelines.

PMID- 24877752
TI  - Self-assembly of cyclo-diphenylalanine peptides in vacuum.
AB  - The diphenylalanine (FF) peptide self-assembles into a variety of nanostructures,
      including hollow nanotubes that form in aqueous solution with an unusually high
      degree of hydrophilic surface area. In contrast, diphenylalanine can also be
      vapor-deposited in vacuum to produce rodlike assemblies that are extremely
      hydrophobic; in this process FF has been found to dehydrate and cyclize to cyclo
      diphenylalanine (cyclo-FF). An earlier study used all-atom molecular dynamics
      (MD) simulations to understand the early stages of the self-assembly of linear-FF
      peptides in solution. Here, we examine the self-assembly of cyclo-FF peptides in
      vacuum and compare it to these previous results to understand the differences
      underlying the two cases. Using all-atom replica exchange MD simulations, we
      consider systems of 50 cyclo-FF peptides and examine free energies along various
      structural association coordinates. We find that cyclo-FF peptides form ladder
      like structures connected by double hydrogen bonds, and that multiple such
      ladders linearly align in a cooperative manner to form larger-scale, elongated
      assemblies. Unlike linear-FFs which mainly assemble through the interplay between
      hydrophobic and hydrophilic interactions, the assembly of cyclo-FFs in vacuum is
      primarily driven by electrostatic interactions along the backbone that induce
      alignment at long-range, followed by van der Waals interactions between side
      chains that become important for close-range packing. While both solution and
      vacuum phase driving forces result in ladder-like structures, the clustering of
      ladders is opposite: linear-FF peptide ladders form assemblies with side-chains
      buried inward, while cyclo-FF ladders point outward. 

PMID- 24877753
TI  - Message sensation and cognition values: factors of competition or integration?
AB  - Using the Activation Model of Information Exposure and Elaboration Likelihood
      Model as theoretical frameworks, this study explored the effects of message
      sensation value (MSV) and message cognition value (MCV) of antismoking public
      service announcements (PSAs) on ad processing and evaluation among young adults,
      and the difference between high sensation seekers and low sensation seekers in
      their perceptions and responses toward ads with different levels of sensation and
      cognition value. A 2 (MSV: high vs. low) * 2 (MCV: high vs. low) * 2 (need for
      sensation: high vs. low) mixed experimental design was conducted. Two
      physiological measures including skin conductance and heart rate were examined.
      Findings of this study show that MSV was not a distraction but a facilitator of
      message persuasiveness. These findings contribute to the activation model. In
      addition, need for sensation moderated the interaction effect of MSV and MCV on
      ad processing. Low sensation seekers were more likely to experience the
      interaction between MSV and MCV than high sensation seekers. Several observations
      related to the findings and implications for antismoking message designs are
      elaborated. Limitations and directions for future research are also outlined. 

PMID- 24877755
TI  - Beyond directed ortho metalation: ruthenium-catalyzed amide-directed C(Ar)-N
      activation/C-C coupling reaction of anthranilamides with organoboronates.
AB  - A new, catalytic, and general methodology for the synthesis of biaryls and
      heterobiaryls by the cross coupling of anthranilamide derivatives (o-NMe2
      benzamides) with aryl boroneopentylates is described. The reaction proceeds under
      catalytic RuH2(CO)(PPh3)3 conditions driven by the activation of the unreactive C
      N bond by amide directing group (DG)-Ru catalyst chelation. High
      regioselectivity, orthogonality with the Suzuki-Miyaura reaction, operational
      simplicity, and convenient scale-up are features of these reactions which may
      lend themselves to industrial applications. 

PMID- 24877754
TI  - The molecular mechanism of curcumol on inducing cell growth arrest and apoptosis
      in Jurkat cells, a model of CD4+ T cells.
AB  - CD4(+) T cells in rheumatoid arthritis (RA) express growth signaling pathway in
      association with deregulated growth and resistance to apoptosis. The janus kinase
      (Jak) 3 and signal transducer and activator of transcription (STAT) pathway play
      a critical role in interleukin-2 (IL-2)-induced CD4(+) T cell proliferation. The
      present study aimed to explore the anti-cell proliferation mechanism of curcumol,
      a pure monomer extracted from Chinese medical plant Rhizoma curcumae. Cell
      proliferation was determined using WST-1 assay after curcumol treatment. The cell
      cycle distribution and Bcl-2 protein expression were assessed by flow cytometry.
      The cellular morphology of apoptosis was evaluated by Hoechst 33258 staining. The
      expressions of phosphorylated-Jak3 (p-Jak3), p-STAT3, and p-STAT5a following IL-2
      stimulation were determined by western blot analysis. The Electrophoretic
      Mobility Shift Assay was used to detect the DNA binding activities of
      transcription factors STAT3 and STAT5. The study results showed that curcumol
      could inhibit the IL-2-induced Jurkat cell proliferation in a concentration- and
      time-dependent manner in vitro. Curcumol could cause cell cycle arrest at the S
      phase, induce cell apoptosis, and inhibit the expression of Bcl-2 in a dose
      dependent manner. Curcumol at 50MUg/mL and Jak3 inhibitor ZM39923 could inhibit
      the phosphorylation of Jak3 and STAT5a. In conclusion, the underlying mechanism
      of curcumol on suppressing CD4(+) T cell proliferation and inducing apoptosis
      might partly be mediated by inhibition of Jak3-STAT5-related molecular activities
      and Bcl-2 expression, respectively; further studies are required in vivo to test
      the use of curcumol as a promising therapeutic option for RA.

PMID- 24877756
TI  - Rv2466c mediates the activation of TP053 to kill replicating and non-replicating
      Mycobacterium tuberculosis.
AB  - The emergence of multidrug- and extensively drug-resistant strains of
      Mycobacterium tuberculosis highlights the need to discover new antitubercular
      agents. Here we describe the synthesis and characterization of a new series of
      thienopyrimidine (TP) compounds that kill both replicating and non-replicating M.
      tuberculosis. The strategy to determine the mechanism of action of these TP
      derivatives was to generate resistant mutants to the most effective compound
      TP053 and to isolate the genetic mutation responsible for this phenotype. The
      only non-synonymous mutation found was a g83c transition in the Rv2466c gene,
      resulting in the replacement of tryptophan 28 by a serine. The Rv2466c
      overexpression increased the sensitivity of M. tuberculosis wild-type and
      resistant mutant strains to TP053, indicating that TP053 is a prodrug activated
      by Rv2466c. Biochemical studies performed with purified Rv2466c demonstrated that
      only the reduced form of Rv2466c can activate TP053. The 1.7 A resolution crystal
      structure of the reduced form of Rv2466c, a protein whose expression is
      transcriptionally regulated during the oxidative stress response, revealed a
      unique homodimer in which a beta-strand is swapped between the thioredoxin
      domains of each subunit. A pronounced groove harboring the unusual active-site
      motif CPWC might account for the uncommon reactivity profile of the protein. The
      mutation of Trp28Ser clearly predicts structural defects in the thioredoxin fold,
      including the destabilization of the dimerization core and the CPWC motif, likely
      impairing the activity of Rv2466c against TP053. Altogether our experimental data
      provide insights into the molecular mechanism underlying the anti-mycobacterial
      activity of TP-based compounds, paving the way for future drug development
      programmes. 

PMID- 24877758
TI  - Risk factors of complications after open abdominal aortic aneurysm repair.

PMID- 24877757
TI  - A proposed model membrane and test method for microneedle insertion studies.
AB  - A commercial polymeric film (Parafilm M((r)), a blend of a hydrocarbon wax and a
      polyolefin) was evaluated as a model membrane for microneedle (MN) insertion
      studies. Polymeric MN arrays were inserted into Parafilm M((r)) (PF) and also
      into excised neonatal porcine skin. Parafilm M((r)) was folded before the
      insertions to closely approximate thickness of the excised skin. Insertion depths
      were evaluated using optical coherence tomography (OCT) using either a force
      applied by a Texture Analyser or by a group of human volunteers. The obtained
      insertion depths were, in general, slightly lower, especially for higher forces,
      for PF than for skin. However, this difference was not a large, being less than
      the 10% of the needle length. Therefore, all these data indicate that this model
      membrane could be a good alternative to biological tissue for MN insertion
      studies. As an alternative method to OCT, light microscopy was used to evaluate
      the insertion depths of MN in the model membrane. This provided a rapid, simple
      method to compare different MN formulations. The use of Parafilm M((r)), in
      conjunction with a standardised force/time profile applied by a Texture Analyser,
      could provide the basis for a rapid MN quality control test suitable for in
      process use. It could also be used as a comparative test of insertion efficiency
      between candidate MN formulations. 

PMID- 24877759
TI  - Methods to evaluate and strategies to improve the biocompatibility of dental
      materials and operative techniques.
AB  - OBJECTIVE: The general aim of this article is to describe the state-of-the-art of
      biocompatibility testing for dental materials, and present new strategies for
      improving operative dentistry techniques and the biocompatibility of dental
      materials as they relate to their interaction with the dentin-pulp complex.
      METHODS: The literature was reviewed focusing on articles related to
      biocompatibilty testing, the dentin-pulp complex and new strategies and materials
      for operative dentistry. For this purpose, the PubMed database as well as 118
      articles published in English from 1939 to 2014 were searched. Data concerning
      types of biological tests and standardization of in vitro and in vivo protocols
      employed to evaluate the cytotoxicity and biocompatibility of dental materials
      were also searched from the US Food and Drug Administration (FDA), International
      Standards Organization (ISO) and American National Standards Institute (ANSI).
      RESULTS: While there is an ongoing search for feasible strategies in the
      molecular approach to direct the repair or regeneration of structures that form
      the oral tissues, it is necessary for professionals to master the clinical
      therapies available at present. In turn, these techniques must be applied based
      on knowledge of the morphological and physiological characteristics of the
      tissues involved, as well as the physical, mechanical and biologic properties of
      the biomaterials recommended for each specific situation. Thus, particularly
      within modern esthetic restorative dentistry, the use of minimally invasive
      operative techniques associated with the use of dental materials with excellent
      properties and scientifically proved by means of clinical and laboratory studies
      must be a routine for dentists. This professional and responsible attitude will
      certainly result in greater possibility of achieving clinical success, benefiting
      patients and dentists themselves. SIGNIFICANCE: This article provides a general
      and critical view of the relations that permeate the interaction between dental
      materials and the dentin-pulp complex, and establish real possibilities and
      strategies that favor biocompatibility of the present and new products used in
      Dentistry, which will certainly benefit clinicians and their patients.

PMID- 24877760
TI  - Unraveling the structure-activity relationship of tomatidine, a steroid alkaloid
      with unique antibiotic properties against persistent forms of Staphylococcus
      aureus.
AB  - Staphylococcus aureus (S. aureus) is responsible for difficult-to-treat and
      relapsing infections and constitutes one of the most problematic pathogens due to
      its multiple resistances to clinically available antibiotics. Additionally, the
      ability of S. aureus to develop small-colony variants is associated with a
      reduced susceptibility to aminoglycoside antibiotics and in vivo persistence. We
      have recently demonstrated that tomatidine, a steroid alkaloid isolated from
      tomato plants, possesses anti-virulence activity against normal strains of S.
      aureus as well as the ability to potentiate the effect of aminoglycoside
      antibiotics. In addition, tomatidine has shown antibiotic activity against small
      colony variants of S. aureus. We herein report the first study of the structure
      activity relationship of tomatidine against S. aureus.

PMID- 24877761
TI  - Short-term effects of air temperature on blood pressure and pulse pressure in
      potentially susceptible individuals.
AB  - BACKGROUND: Only few epidemiological studies have investigated the association
      between air temperature and blood pressure (BP) or pulse pressure (PP), with
      inconsistent findings. We examined whether short-term changes in air temperature
      were associated with changes in BP or PP in three different populations. METHODS:
      Between March 2007 and December 2008, 371 systolic and diastolic BP measurements
      were collected in 30 individuals with type-2 diabetes mellitus (T2D), 30 persons
      with impaired glucose tolerance and 42 healthy individuals without a metabolic
      disorder from Augsburg, Germany. Hourly means of ambient meteorological data were
      obtained from a fixed measurement station. Personal temperature measurements were
      conducted using data loggers. Temperature effects were evaluated using additive
      mixed models adjusting for time trend and relative humidity. RESULTS: Decreases
      in air temperature were associated with an increase in systolic BP, diastolic BP
      and PP in individuals with T2D. For example, a 1 degrees C decrease in ambient
      temperature was associated with an immediate increase in systolic BP of 1.0 mmHg
      (95%-confidence interval: [0.5;1.4]mmHg). Effects of personally measured air
      temperature were similar. Temperature effects were modified by age, body mass
      index, gender, antihypertensive medication and whereabouts, such as being
      indoors. CONCLUSIONS: We observed associations between decreases in air
      temperature and increases in BP as well as PP in persons with T2D indicating that
      these people might be potentially more susceptible to changes in air temperature.
      Our findings may provide a hypothesis for a mechanism between air temperature
      decreases and short-term increases of cardiovascular events.

PMID- 24877763
TI  - Bedside emergency ultrasound in a case of acute parotid duct sialolithiasis.
AB  - BACKGROUND: Sialolithiasis with salivary gland obstruction can mimic more
      frequently occurring illnesses such as facial and dental infection and abscess.
      It is often difficult to discern the etiology of facial pain and swelling on
      physical examination alone, requiring advanced imaging in the emergency
      department. CASE REPORT: We describe the case of a 37-year-old man who presented
      with 5 days of worsening unilateral facial pain and swelling. Use of bedside
      emergency ultrasound by an emergency physician (EP) led to an appropriate
      diagnosis of parotid duct sialolithiasis. Why Should an Emergency Physician Be
      Aware of This? Use of bedside emergency ultrasound performed by a trained EP
      successfully diagnosed symptomatic sialolithiasis of the parotid duct in the
      emergency department without the need for computed tomography. The utility of
      bedside emergency ultrasound in the evaluation of sialolithiasis and the outcomes
      of our case are discussed here.

PMID- 24877762
TI  - Tropheryma whipplei and Whipple's disease.
AB  - Since its identification, information concerning Tropheryma whipplei, the
      causative agent of Whipple's disease (WD), has increased. Although T. whipplei is
      commonly infecting humans, WD is rare. The bacterium is most likely transmitted
      among humans via the oro-oral and the feco-oral routes. Infections result in
      chronic conditions such as asymptomatic carriage, disseminated Whipple's disease,
      which is usually preceded by arthralgias, and localized infections, such as
      endocarditis or encephalitis. T. whipplei is associated with acute infections
      including gastroenteritis, pneumonia, and/or bacteremia. Screening, based on the
      combined analyses of saliva and stool specimens using specific quantitative PCR,
      is useful if WD is suspected. Doxycycline and hydroxychloroquine for 12 months is
      the best treatment for WD; it should be followed by life-long treatment with
      doxycycline, as potentially fatal relapses can occur. T. whipplei seems to be an
      opportunistic bacterium that causes chronic infections in susceptible patients
      with as yet unknown predisposing factors. 

PMID- 24877764
TI  - The impact of pandemic A(H1N1)pdm09 influenza and vaccine-associated adverse
      events on parental attitudes and influenza vaccine uptake in young children.
AB  - INTRODUCTION: Parental attitudes towards vaccination significantly influence
      vaccine uptake. The A(H1N1)pdm09 influenza pandemic was followed in 2010 by an
      unprecedented increase in febrile reactions in children receiving trivalent
      inactivated influenza vaccine manufactured by bioCSL. Uptake of TIV in children
      <5 years in Western Australia (WA) decreased in 2010 and has remained low. The
      impact of pandemic A(H1N1)pdm09 and adverse-events on parental attitudes towards
      vaccination is uncertain. MATERIALS AND METHODS: A parental attitudes survey
      towards influenza illness and vaccination was conducted as part of the West
      Australian Influenza Vaccine Effectiveness study. Vaccination status was assessed
      by parental interview and confirmed by the national register and/or vaccine
      providers. Parental attitudes from vaccinated and unvaccinated children and
      attitudes in 2008-2009 and 2010-2012 were compared. Principal Component Analysis
      was conducted to determine core attitudes that influenced vaccine uptake.
      RESULTS: Vaccination history and parental attitude surveys were available from
      2576 children. Parents of fully vaccinated children less frequently stated that
      influenza was a mild disease, more frequently stated that influenza vaccine was
      safe and were less frequently worried about vaccine side effects. Uptake of
      influenza vaccine decreased significantly from 2010 onwards. From 2010, parents
      were less concerned about severe influenza, but more concerned about vaccine side
      effects and safety. Despite this significant shift in attitudes towards influenza
      vaccine, parental acceptance of vaccines on the national immunisation program did
      not change. Principal Component Analysis revealed that attitudes around vaccine
      safety and efficacy were the most important attitudes impacting on vaccine
      uptake. CONCLUSIONS: Parental attitudes to influenza vaccine changed from 2010.
      Confidence in the WA preschool influenza vaccination program remains low yet
      appeared unchanged for other vaccines. Restoring public confidence in childhood
      influenza vaccination is needed before uptake can be improved.

PMID- 24877765
TI  - Induction of CD8+ T-cell responses against subunit antigens by the novel cationic
      liposomal CAF09 adjuvant.
AB  - Vaccines inducing cytotoxic T-cell responses are required to achieve protection
      against cancers and intracellular infections such as HIV and Hepatitis C virus.
      Induction of CD8+ T cell responses in animal models can be achieved by the use of
      viral vectors or DNA vaccines but so far without much clinical success. Here we
      describe the novel CD8+ T-cell inducing adjuvant, cationic adjuvant formulation
      (CAF) 09, consisting of dimethyldioctadecylammonium (DDA)-liposomes stabilized
      with monomycoloyl glycerol (MMG)-1 and combined with the TLR3 ligand, Poly(I:C).
      Different antigens from tuberculosis (TB10.3, H56), HIV (Gag p24), HPV (E7) and
      the model antigen ovalbumin were formulated with CAF09 and administering these
      vaccines to mice resulted in a high frequency of antigen-specific CD8+ T cells.
      CAF09 was superior in its ability to induce antigen-specific CD8+ T cells as
      compared to other previously described CTL-inducing adjuvants, CAF05
      (DDA/trehalose dibehenate (TDB)/Poly(I:C)), Aluminium/monophosphoryl lipid-A
      (MPL) and Montanide/CpG/IL-2. The optimal effect was obtained when the CAF09
      adjuvanted vaccine was administered by the i.p. route, whereas s.c.
      administration primed limited CD8+ T-cell responses. The CD4+ T cells induced by
      CAF09 were mainly of an effector-memory-like phenotype and the CD8+ T cells were
      highly cytotoxic. Finally, in a mouse therapeutic skin tumor model, the HPV-16 E7
      antigen formulated in CAF09 significantly reduced the growth of already
      established subcutaneous E7-expressing TC-1 tumors in 38% of the mice and in a
      corresponding prophylactic model 100% of the mice were protected. Thus, CAF09 is
      a potent new adjuvant which is able to induce CD8+ T-cell responses against
      several antigens and to enhance the protective efficacy of an E7 vaccine both in
      a therapeutic and in a prophylactic tumor model.

PMID- 24877766
TI  - Modern adjuvants do not enhance the efficacy of an inactivated African swine
      fever virus vaccine preparation.
AB  - African swine fever (ASF) is among the most devastating viral diseases of pigs.
      In recent years, the disease has spread alarmingly. Despite intensive research
      activities, promising vaccine candidates are still lacking. For this reason, a
      study was undertaken to re-assess inactivated ASFV preparations with state-of-the
      art adjuvants. Inactivated preparations of ASF virus (ASFV) "Armenia08" were
      adjuvanted with either PolygenTM or Emulsigen((r))-D, respectively, and used to
      immunize six weaner pigs two times with a three-week interval. Six weeks after
      the first immunization, animals were challenged with the homologues highly
      virulent ASFV. Although ASFV-specific antibodies were detectable in all but one
      vaccinated animal prior to challenge, no protective effect of immunization was
      observed. All animals developed acute-lethal ASF and had to be euthanized within
      eleven days post challenge. A slightly accelerated clinical course in vaccinees
      could even indicate an antibody dependent enhancement, which could also influence
      efficacy of other vaccine approaches.

PMID- 24877767
TI  - Oral immunization with Lactococcus lactis-expressing EspB induces protective
      immune responses against Escherichia coli O157:H7 in a murine model of
      colonization.
AB  - Enterohemorrhagic Escherichia coli (EHEC) have been responsible for several
      outbreaks of hemolytic-uremic syndrome (HUS) worldwide. HUS is the most common
      cause of acute renal failure in children and results in fatalities as high as 50%
      in the elderly. Currently, neither a specific treatment nor a vaccine is
      available for EHEC. Lactococcus lactis is a generally regarded as safe "GRAS"
      bacterium that offers a valuable platform for oral vaccine delivery. Toward the
      development of an oral vaccine against EHEC, we have previously constructed a
      recombinant L. lactis strain expressing the EHEC antigen, EspB in the cytoplasmic
      compartment. However, oral immunization of mice with this strain induced weak
      priming of the immune system. This outcome was attributed to the rather low
      levels of EspB expressed by this recombinant strain. Therefore, in the present
      study we optimized the expression of EspB in L. lactis by secreting the antigen
      either under constitutive or nisin-inducible control. Indeed, oral immunization
      of mice with the EspB-secreting strains successfully induced specific mucosal and
      systemic antibody responses. These responses were associated with mixed Th1/Th2
      cell responses in Peyer's Patches and mesenteric lymph nodes. Moreover, immunized
      mice exhibited significant protection against E. coli O157:H7 colonization, as
      indicated by the reduced amount and/or duration of the bacterial fecal shedding.
      Our results demonstrate the protective potential of EspB as an oral vaccine
      against EHEC infection. Additionally, the study demonstrates the efficient
      delivery of recombinant EspB by the "GRAS" bacterium, L. lactis. The safety
      profile of L. lactis as a vaccine vehicle can particularly be beneficial to
      children and elderly as high-risk groups for HUS incidence. 

PMID- 24877768
TI  - A 5-year Chlamydia vaccination programme could reverse disease-related koala
      population decline: predictions from a mathematical model using field data.
AB  - BACKGROUND: Many koala populations around Australia are in serious decline, with
      a substantial component of this decline in some Southeast Queensland populations
      attributed to the impact of Chlamydia. A Chlamydia vaccine for koalas is in
      development and has shown promise in early trials. This study contributes to
      implementation preparedness by simulating vaccination strategies designed to
      reverse population decline and by identifying which age and sex category it would
      be most effective to target. METHODS: We used field data to inform the
      development and parameterisation of an individual-based stochastic simulation
      model of a koala population endemic with Chlamydia. The model took into account
      transmission, morbidity and mortality caused by Chlamydia infections. We
      calibrated the model to characteristics of typical Southeast Queensland koala
      populations. As there is uncertainty about the effectiveness of the vaccine in
      real-world settings, a variety of potential vaccine efficacies, half-lives and
      dosing schedules were simulated. RESULTS: Assuming other threats remain constant,
      it is expected that current population declines could be reversed in around 5-6
      years if female koalas aged 1-2 years are targeted, average vaccine protective
      efficacy is 75%, and vaccine coverage is around 10% per year. At lower vaccine
      efficacies the immunological effects of boosting become important: at 45% vaccine
      efficacy population decline is predicted to reverse in 6 years under optimistic
      boosting assumptions but in 9 years under pessimistic boosting assumptions.
      Terminating a successful vaccination programme at 5 years would lead to a rise in
      Chlamydia prevalence towards pre-vaccination levels. CONCLUSION: For a range of
      vaccine efficacy levels it is projected that population decline due to endemic
      Chlamydia can be reversed under realistic dosing schedules, potentially in just 5
      years. However, a vaccination programme might need to continue indefinitely in
      order to maintain Chlamydia prevalence at a sufficiently low level for population
      growth to continue.

PMID- 24877769
TI  - Red blood cells donate electrons to methylene blue mediated chemical reduction of
      methemoglobin compartmentalized in liposomes in blood.
AB  - Electron-energy-rich coenzymes in cells, NADH and NADPH, are re-energized
      repeatedly through the Embden-Meyerhof and pentose-phosphate glycolytic pathways,
      respectively. This study demonstrates extraction of their electron energies in
      red blood cells (RBCs) for in vivo extracellular chemical reactions using an
      electron mediator shuttling across the biomembrane. Hemoglobin-vesicles (HbVs)
      are an artificial oxygen carrier encapsulating purified and concentrated Hb
      solution in liposomes. Because of the absence of a metHb-reducing enzymatic
      system in HbV, HbO2 gradually autoxidizes to form metHb. Wistar rats received HbV
      suspension (10 mL/kg body weight) intravenously. At the metHb level of around
      50%, methylene blue [MB(+); 3,7-bis(dimethylamino)phenothiazinium chloride] was
      injected. The level of metHb quickly decreased to around 16% in 40 min, remaining
      for more than 5 h. In vitro mixing of HbV/MB(+) with RBCs recreated the in vivo
      metHb reduction, but not with plasma. NAD(P)H levels in RBCs decreased after
      metHb reduction. The addition of glucose facilitated metHb reduction. Liposome
      encapsulated NAD(P)H, a model of RBC, reduced metHb in HbV in the presence of
      MB(+). These results indicate that (i) NAD(P)H in RBCs reacts with MB(+) to
      convert it to leukomethylene blue (MBH); (ii) MB(+) and MBH shuttle freely
      between RBC and HbV across the hydrophobic lipid membranes; and (iii) MBH is
      transferred into HbV and reduces metHb in HbV. Four other electron mediators with
      appropriate redox potentials appeared to be as effective as MB(+) was, indicating
      the possibility for further optimization of electron mediators. We established an
      indirect enzymatic metHb reducing system for HbV using unlimited endogenous
      electrons created in RBCs in combination with an effective electron mediator that
      prolongs the functional lifespan of HbV in blood circulation. 

PMID- 24877771
TI  - Increase in the protein-bound form of glutathione in human blood after the oral
      administration of glutathione.
AB  - The present study examined the impact of the supplementation of glutathione
      (GSH), gamma-L-glutamyl-L-cysteinyl-glycine, on human blood GSH levels. Healthy
      human volunteers were orally supplemented with GSH (50 mg/kg body weight). Venous
      blood was collected from the cubital vein before and after ingestion. Plasma was
      mixed with 3 volumes of ethanol. The supernatant and precipitate were used for
      the deproteinized and protein fractions of plasma, respectively. Blood cell and
      plasma fractions were pretreated with 5% trichloroacetic acid-2% 2
      mercaptoethanol to reduce the oxidized form of GSH and liberate protein-bound
      GSH. The 2-mercaptoethanol-pretreated GSH was determined by precolumn
      derivatization with 6-aminoquinolyl-N-hydroxy succinimidyl carbamate and liquid
      chromatography-tandem mass spectrometry. There was no significant difference in
      GSH contents in the deproteinized fraction of plasma and blood cell fraction
      after GSH ingestion. However, the GSH contents in the protein-bound fraction of
      plasma significantly (P<0.01) increased from 60 to 120 min after GSH
      supplementation.

PMID- 24877774
TI  - [A link between research and routine practice].

PMID- 24877770
TI  - Hidden diversity and evolutionary trends in malacosporean parasites (Cnidaria:
      Myxozoa) identified using molecular phylogenetics.
AB  - Malacosporeans represent a small fraction of myxozoan biodiversity with only two
      genera and three species described. They cycle between bryozoans and freshwater
      fish. In this study, we (i) microscopically examine and screen different
      freshwater/marine fish species from various geographic locations and habitats for
      the presence of malacosporeans using PCR; (ii) study the morphology, prevalence,
      host species/habitat preference and distribution of malacosporeans; (iii) perform
      small subunit/large subunit rDNA and Elongation factor 2 based phylogenetic
      analyses of newly gathered data, together with all available malacosporean data
      in GenBank; and (iv) investigate the evolutionary trends of malacosporeans by
      mapping the morphology of bryozoan-related stages, host species, habitat and
      geographic data on the small subunit rDNA-based phylogenetic tree. We reveal a
      high prevalence and diversity of malacosporeans in several fish hosts in European
      freshwater habitats by adding five new species of Buddenbrockia and
      Tetracapsuloides from cyprinid and perciform fishes. Comprehensive phylogenetic
      analyses revealed that, apart from Buddenbrockia and Tetracapsuloides clades, a
      novel malacosporean lineage (likely a new genus) exists. The fish host species
      spectrum was extended for Buddenbrockia plumatellae and Buddenbrockia sp. 2. Co
      infections of up to three malacosporean species were found in individual fish.
      The significant increase in malacosporean species richness revealed in the
      present study points to a hidden biodiversity in this parasite group. This is
      most probably due to the cryptic nature of malacosporean sporogonic and
      presporogonic stages and mostly asymptomatic infections in the fish hosts. The
      potential existence of malacosporean life cycles in the marine environment as
      well as the evolution of worm- and sac-like morphology is discussed. This study
      improves the understanding of the biodiversity, prevalence, distribution, habitat
      and host preference of malacosporeans and unveils their evolutionary trends. 

PMID- 24877772
TI  - Oxidative stress, protein glycation and nutrition--interactions relevant to
      health and disease throughout the lifecycle.
AB  - Protein glycation has been studied for over a century now and plays an important
      role in disease pathogenesis throughout the lifecycle. Strongly related to
      diabetic complications, glycation of Hb has become the gold standard method for
      diabetes diagnosis and monitoring. It is however attracting attention in
      normoglycaemia as well lately. Longitudinal studies increasingly suggest a
      positive relationship between glycation and the risk of chronic diseases in
      normoglycaemic individuals, but the mechanisms behind this association remain
      unclear. The interaction between glycation and oxidative stress may be
      particularly relevant in the normoglycaemic context, as suggested by recent
      epidemiological and in vitro evidence. In that context nutritional and lifestyle
      factors with an influence on redox status, such as smoking, fruit and vegetable
      and antioxidants consumption, may have the capacity to promote or inhibit
      glycation. However, experimental data from controlled trials are lacking the
      quality and rigour needed to reach firm conclusions. In the present review, we
      discuss the importance of glycation for health through the lifecycle and focus on
      the importance of oxidative stress as a driver for glycation. The importance of
      nutrition to modulate glycation is discussed, based on the evidence available and
      recommendations towards higher quality future research are made. 

PMID- 24877775
TI  - [Adolescents in Web 2.0: risks and chances ].
AB  - That almost all adolescents possess an individual access to the internet and that
      they use it every day, lays the foundation for the improved means of self
      presentation and participation that are known by the notion of Web 2.0. Social
      networks and other interactive internet formats give rise to new risks like cyber
      mobbing which is the topic of three contributions. At the same time, Web 2.0
      offers chances in the form of online counseling and online therapy that cater to
      the preferences of media-friendly target group of adolescents.

PMID- 24877777
TI  - [How do adolescents in Germany define cyberbullying? A focus-group study of
      adolescents from a German major city].
AB  - A steadily growing number of empirical research on cyberbullying exists retaining
      the traditional definition of bullying. However, whether this scientific and
      theoretical definition represents youths' perceptions and experiences with
      cyberbullying is a subject of further investigation. Scenarios of cyberbullying
      incidents were used and later discussed in three focus groups with 20 adolescents
      (55 % boys, 45 % girls, 11-16 years old). Thematic and content analyses laid
      focus on the following questions: (1) Which terms are used by the adolescents to
      describe the behaviors in the incidents? (2) What are the roles of traditional
      bullying definition criteria (i. e. intention, repetition, and power imbalance)
      and two additional cyberbullying-specific criteria (i. e. anonymity and
      publicity)? (3) How are the behaviors perceived in comparison to each other?
      Results show that German adolescents perceive "cybermobbing" as the best term to
      describe the presented incidents. Impersonation was not perceived as
      cyberbullying by the adolescents, but rather viewed as a criminal act. In
      addition, adolescents perceived the intent to harm, the impact on the victim, and
      repetition relevant for defining cyberbullying. Moreover, analyses revealed an
      interdependence between criteria which suggests that anonymity and publicity have
      an effect on the severity of the behavior, however they were not essential for
      the definition of cyberbullying.

PMID- 24877776
TI  - [Coping of cybervictimization in adolescence - emotional and behavioral reactions
      to cyberbullying ].
AB  - The experience of cybervictimization is related to health, psychological, and
      behavioral problems among children and adolescents. Up to today research is
      scarce, how the persons affected by cybervictimization react and which
      determinants influence the choice for social, problem-focused, technical, or
      helpless coping behavior. The current online study with 428 adolescents considers
      age, sex, mean internet use, frequency of victimization, roles in cyberbullying,
      and emotional reactions to cybervictimization as potential determinants of the
      mentioned coping strategies. Based on the participant role approach, roles of
      cyberbullies, cybervictims, defenders or outsiders are frequently changing.
      Logistic regression analyses point out the important relevance of emotional
      reactions like anger or helplessness and the roles as cyberbully-victim or
      outsider. Further, younger participants reported cybervictimization more often,
      while the frequency of cybervictimization and sex did not and internet use only
      partially predict coping strategies. These findings corroborate the relevance of
      emotional reactions and the roles in the process of cyberbullying. As a starting
      point for prevention and intervention of cybervictimization, we suggest emotion
      regulation, teaching of technical coping behaviors as well as reflexion of roles
      in the context of cyberbullying. If feasible, different stakeholders should be
      engaged in this process: adolescents, parents, educational staff inside and
      outside of schools, experts from counseling and therapy as well as internet and
      mobile phone service providers.

PMID- 24877778
TI  - [Promotion of media competence and prevention of cyberbullying using the
      Medienhelden program: results from an evaluation study ].
AB  - The manualized Medienhelden (engl. Media Heroes) program (Schultze-Krumbholz,
      Zagorscak, Siebenbrock, Scheithauer, 2012) is implemented in the school
      environment either as a ten-week program during lessons (curriculum; IGL) or as a
      single project day with reduced content of the long version (IGK). In consecutive
      lessons, topics of the program are, for example: definition of cyberbullying, its
      negative impact, how to protect oneself on the internet, and opportunities to
      react in appropriate ways. The program utilizes mainly cognitive-behavioral
      methods. In the present contribution the program and selected results from a
      controlled, pre-follow-up evaluation study with 570 adolescents (Ncontrolgroup =
      289, NIGK = 98 and NIGL = 183), from one general high school and four college
      preparatory high schools from a German major city will be presented. Results show
      that cyberbullying decreased in both intervention groups (project day,
      curriculum) compared to the control group while at the same time an increase of
      social competencies, self-esteem, and subjective health was observed. These
      effects were more pronounced for the curriculum intervention group. An opposite
      pattern was found for the control group: Cyberbullying and empathy worsened, and
      no change was found for perspective-taking, self-esteem, and subjective health.
      The program shows both preventive and intervention effects.

PMID- 24877779
TI  - [Internet-based approaches in prevention and treatment of depressive symptoms in
      adolescents and young adults ].
AB  - Epidemiological findings indicate that up to 18.5 % of the German adolescents
      suffer from depressive symptoms and that younger adults display the highest risk
      for relevant symptoms of depression (9.9 %) within the German adult population.
      Internet-based interventions have been shown to be useful for preventing and
      treating depression and are more easily disseminated in internet-savvy
      generations. Available programs are usually based on principles of cognitive
      behavioural therapy. They differ significantly with regard to target groups,
      structure, content, degree of guidance provided by online-coaches and evidence
      for their efficacy. Whereas some studies could not prove the use of the trainings
      there are others that show large effect sizes (up to d = 0.84) for the reduction
      of depressive symptoms. In Germany there are some online counseling programs for
      children and adolescents in (acute) crises available. However, at this point no
      structured intervention program for the treatment of depression exists.

PMID- 24877783
TI  - Pathological and parasitological traits in experimentally infected cats with
      Gnathostoma binucleatum (Spirurida: Gnathostomatidae).
AB  - This study aims to describe some of the unknown pathological and parasitological
      traits of experimental feline gnathostomosis. Thirteen female cats were orally
      inoculated with 30 advanced third-stage Gnathostoma binucleatum larvae and were
      euthanized at various post-infection (p.i.) periods. Clinically, the cats
      presented with nausea, vomiting, abdominal pain and other nonspecific signs. None
      of the cats shed eggs in their fecal matter. One cat, euthanized at 6 months
      p.i., developed a fibrous vascular nodule 2-3 cm in diameter within its gastric
      wall. The nodule contained caverns filled with mucous and bloody fluid as well as
      a juvenile worm. The histological characteristics of the nodule were observed,
      and the morphology of the juvenile worm was revealed using scanning electron
      microscopy. Another cat, euthanized at 10 months p.i., was found to have a larva
      within its diaphragm. Infected cats developed increased antibody titers against
      antigens of G. binucleatum adults and larvae beginning in the first month p.i.,
      and these titers were maintained until the end of the experiment, suggesting the
      presence of undetected migrating larvae. The low number of cats with parasites
      and poor development of the parasites found suggest that cats have a low
      susceptibility to infection by G. binucleatum and cast doubt on the importance of
      domestic cats in maintaining the biological cycle of this parasite in nature.

PMID- 24877784
TI  - Superinfection of sows with Cystoisospora suis ante partum leads to a milder
      course of cystoisosporosis in suckling piglets.
AB  - Cystoisospora (syn. Isospora) suis is a leading cause of diarrheal disease in
      neonatal piglets. To address the possibility of maternal immunization against C.
      suis infection six non-naive pregnant sows were superinfected with 100,000
      oocysts 2 weeks ante partum and compared to non-superinfected animals. Their
      piglets were infected with 1000 oocysts on the third day of life. Clinical and
      parasitological parameters as well as antibody titers in colostrum/milk and blood
      of sows and in the blood of piglets were evaluated by IFAT against sporozoites
      and merozoites from 2 weeks ante partum until the 35th day after birth. For IFAT
      two different invasive stages of C. suis were used to find possible differences
      between the immune response against the initially infectious stages (sporozoites)
      and later occurring asexual developmental stages (merozoites), which might be
      responsible for persisting/extraintestinal infections. IFN-gamma production of
      PBMC and piglet splenocytes was determined by ELISPOT. Maternal superinfection
      resulted in increased titers of IgA, IgM and IgG in colostrum and milk as well as
      in the blood of sows and their piglets. Oocyst shedding and diarrhea were
      observed in the offspring of both groups, but piglets of superinfected sows
      showed significantly reduced oocyst shedding and less diarrhea. This protective
      effect was correlated with increased titers of antibodies, especially IgA, in
      colostrum, milk and blood serum of sows and piglets, and with the reactivity of
      splenocytes to parasite antigen. Superinfection of sows ante partum could
      partially protect piglets against the clinical outcome of experimental infection.
      Both colostrum and milk contain maternal protective substances as the effect of
      protection was highly correlated with antibody titers during the first 2 weeks of
      life. IgA in different substrates may serve as a marker for the level of
      protection against clinical cystoisosporosis. 

PMID- 24877785
TI  - Seroprevalence of Toxoplasma gondii and Encephalitozoon cuniculi in rabbits from
      different farming systems.
AB  - The breeding of domestic rabbit (Oryctolagus cuniculus) for human consumption has
      a long tradition mainly in European and Asian countries. Infections that can
      affect the production of meat or even be transmitted from animals to humans are
      important to monitor, especially for public health reasons as well as for their
      impact on animals health. This study aimed to collect sera from rabbits bred in
      different conditions and test the presence of Toxoplasma gondii and
      Encephalitozoon cuniculi antibodies. Whether infections were active or latent was
      assessed by determining the occurrence of IgM or IgM together with IgG antibodies
      which indicated active infection whereas latent infection was characterized by
      finding IgG antibodies only. An ELISA test was performed with 1883 sera samples
      collected throughout the Czech and Slovak Republics. The seroprevalence of T.
      gondii in 902 samples from 6 commercial farms (CF) was very low with only 4
      rabbits (0.4%) being positive. In total 99 (10.1%) individuals out of 981 samples
      from 29 household farms (HF) were positive for T. gondii antibodies. Only 2 (50%)
      of the T. gondii positive CF rabbits had active infections while the rest were
      latently infected. The serological results showed that 35 (35.4%) rabbits from
      the T. gondii positive HF group suffered from active infection. Out of CF samples
      185 (20.5%) were positive for E. cuniculi. Antibodies of E. cuniculi were
      detected in 497 (50.7%) HF rabbits. Active E. cuniculi infections were determined
      in 85.9% of CF and 56.3% of HF rabbits; respectively. Interestingly, the E.
      cuniculi positive rabbits were significantly more often positive for anti-T.
      gondii antibodies in comparison to E. cuniculi negative individuals. Prevalence
      of T. gondii in CF rabbits was negligible. According to our results meat of HF
      rabbits still poses a risk of T. gondii infection. Nevertheless, the risk is on
      its lowest level in 20 years which is apparently caused due to changes in feeding
      practices. The occurrence of E. cuniculi antibodies was significantly lower in
      rabbits from commercial farms, apparently because of better hygiene conditions. 

PMID- 24877786
TI  - Coprologically diagnosing Anoplocephala perfoliata in the presence of A. magna.
AB  - Current copro-diagnostic tests for Anoplocephala perfoliata show high variation
      in their sensitivity and given the morphological similarity of Anoplocephala spp.
      eggs, this could be related to the presence of Anoplocephala magna alone or co
      existing with A. perfoliata. In the present study, coprology was significantly
      more sensitive (p<0.01) at detecting A. magna than A. perfoliata. This difference
      was independent of the parasite burden and was greater when testing was limited
      to horses with mature or gravid tapeworms. A. magna infection was strongly linked
      to young horses (<= 2 years). The eggs of A. magna are smaller. Using 15 and 70
      MUm cut-offs for oncosphere diameter and the major shell bisector length,
      respectively, the eggs of A. perfoliata were identified with 100% sensitivity,
      97% specificity and 98% sensitivity, 84% specificity. The use of these two
      morphometric variables would therefore be useful for the copro-identification of
      A. perfoliata in countries where both species coexist.

PMID- 24877787
TI  - Comparison of two coproparasitological techniques for the detection of
      Platynosomum sp. infection in cats.
AB  - Platynosomum sp. is the etiologic agent of platynosomiasis, a hepatic disease
      that affects domestic cats. The parasite develops in the bile ducts and
      gallbladder, causing severe hepato-biliary disease. Considering the importance of
      the disease and the increase in the number of households with cats, the aim of
      this study was to compare two different techniques for the detection of the
      parasite's eggs and to assess the frequency of Platynosomum sp. infection in
      cats. Forty fecal samples from cats of different ages, from an animal shelter in
      the city of Salvador, Bahia State, Brazil, were subjected to two different
      techniques: a centrifugal fecal flotation procedure in Sheather's sugar solution
      and centrifugal sedimentation in formalin-ether solution. Positive results were
      found for 12.5% of the samples using the centrifugal fecal flotation assay,
      whereas all samples were negative when employing the centrifugal sedimentation
      test. The results suggest that this parasite can be found infecting cats in
      Salvador city and that centrifugal fecal flotation in sugar solution can be a
      more suitable detection of the parasite's eggs at fecal samples. Therefore,
      platynosomiasis must be included in the diseases to be studied routinely in
      domestic felids. 

PMID- 24877788
TI  - Low level deltamethrin resistance in ticks from cattle of Kerala, a south Indian
      state.
AB  - The deltamethrin resistance status in Rhipicephalus (Boophilus) annulatus and R.
      (B.) microplus ticks collected from cattle of five organized farms of Kerala,
      south India was evaluated. Resistance was characterized using biological (larval
      packet test), biochemical (esterase enzyme activity assay) and molecular tools
      (PCR amplification and sequencing of deltamethrin resistance-associated genes).
      Characterization of field isolates revealed level I resistance in ticks collected
      from four out of five farms. Elevated level of alpha/beta esterase activity was
      not recorded in isolates showing level I resistance. Previously reported point
      mutations in the carboxyl esterase (G1120A) and sodium channel (T2134A and C190A)
      genes were not observed in any of the field isolates. The present study showed a
      low level (level I) resistance is developed in the most economically important
      ticks infesting cattle of this state and it cautions the development of large
      scale resistance in future. 

PMID- 24877789
TI  - Further thoughts on "Asymptomatic dogs are highly competent to transmit
      Leishmania (Leishmania) infantum chagasi to the natural vector".

PMID- 24877790
TI  - Fluorescence correlation spectroscopy and nonlinear stochastic reaction
      diffusion.
AB  - The currently existing theory of fluorescence correlation spectroscopy (FCS) is
      based on the linear fluctuation theory originally developed by Einstein, Onsager,
      Lax, and others as a phenomenological approach to equilibrium fluctuations in
      bulk solutions. For mesoscopic reaction-diffusion systems with nonlinear chemical
      reactions among a small number of molecules, a situation often encountered in
      single-cell biochemistry, it is expected that FCS time correlation functions of a
      reaction-diffusion system can deviate from the classic results of Elson and Magde
      [ Biopolymers 1974, 13, 1 - 27]. We first discuss this nonlinear effect for
      reaction systems without diffusion. For nonlinear stochastic reaction-diffusion
      systems, there are no closed solutions; therefore, stochastic Monte Carlo
      simulations are carried out. We show that the deviation is small for a simple
      bimolecular reaction; the most significant deviations occur when the number of
      molecules is small and of the same order. Our results show that current linear
      FCS theory could be adequate for measurements on biological systems that contain
      many other sources of uncertainties. At the same time, it provides a framework
      for future measurements of nonlinear, fluctuating chemical reactions with high
      precision FCS. Extending Delbruck-Gillespie's theory for stochastic nonlinear
      reactions with rapid stirring to reaction-diffusion systems provides a mesoscopic
      model for chemical and biochemical reactions at nanometric and mesoscopic levels,
      such as a single biological cell.

PMID- 24877791
TI  - The benefits and risks of telling and listening to stories of difficulty over
      time: experimentally testing the expressive writing paradigm in the context of
      interpersonal communication between friends.
AB  - The overarching goal of the current study was to determine the impact of talking
      interpersonally over time on emerging adults' individual and relational health.
      Using an expressive writing study design (see Frattaroli, 2006), we assessed the
      degree to which psychological health improved over time for college students who
      told and listened to stories about friends' current difficulties in comparison
      with tellers in control conditions. We also investigated the effects on tellers'
      and listeners' perceptions of each other's communication competence, communicated
      perspective-taking, and the degree to which each threatened the other's face
      during the interaction over time to better understand the interpersonal
      communication complexities associated with talking about difficulty over time.
      After completing prestudy questionnaires, 49 friend pairs engaged in three
      interpersonal interactions over the course of 1 week wherein one talked about and
      one listened to a story of difficulty (treatment) or daily events (control). All
      participants completed a poststudy questionnaire 3 weeks later. Tellers' negative
      affect decreased over time for participants exposed to the treatment group,
      although life satisfaction increased and positive affect decreased across time
      for participants regardless of condition. Perceptions of friends' communication
      abilities decreased significantly over time for tellers. The current study
      contributes to the literature on expressive writing and social support by
      shedding light on the interpersonal implications of talking about difficulty, the
      often-overlooked effects of disclosure on listeners, and the health effects of
      talking about problems on college students' health. 

PMID- 24877792
TI  - Understanding and modeling removal of anionic organic contaminants (AOCs) by
      anion exchange resins.
AB  - Ionic organic contaminants (OCs) are a growing concern for water treatment and
      the environment and are removed inefficiently by many existing technologies. This
      study examined removal of anionic OCs by anion exchange resins (AXRs) as a
      promising alternative. Results indicate that two polystyrene AXRs (IRA910 and
      IRA96) have higher sorption capacities and selectivity than a polyacrylate resin
      (A860). For the polystyrene resins, selectivity follows: phenolates >= aromatic
      dicarboxylates > aromatic monocarboxylates > benzenesulfonate > aliphatic
      carboxylates. This trend can be explained based on hydration energy, the number
      of exchange groups, and aromaticity and hydrophobicity of the nonpolar moiety
      (NPM) of the anions. For A860, selectivity only varies within a narrow range
      (0.13-1.64). Despite the importance of the NPM of the anions, neutral solutes
      were sorbed much less, indicating synergistic combinations of electrostatic and
      nonelectrostatic interactions in the overall sorption. By conducting multiple
      linear regression between Abraham's descriptors and nature log of selectivity,
      induced dipole-related interactions and electrostatic interactions were found to
      be the most important interaction forces for sorption of the anions, while solute
      H-bond basicity has a negative effect. A predictive model was then developed for
      carboxylates and phenolates based on the poly parameter linear free energy
      relationships established for a diverse range of 16 anions and 5 neutral solutes,
      and was validated by accurate prediction of sorption of five test solutes within
      a wide range of equilibrium concentrations and that of benzoate at different pH. 

PMID- 24877794
TI  - Point/counterpoint. Medical physics residents should be placed using a matching
      program.

PMID- 24877795
TI  - Dosimetric effects caused by couch tops and immobilization devices: report of
      AAPM Task Group 176.
AB  - The dosimetric impact from devices external to the patient is a complex
      combination of increased skin dose, reduced tumor dose, and altered dose
      distribution. Although small monitor unit or dose corrections are routinely made
      for blocking trays, ion chamber correction factors, e.g., accounting for
      temperature and pressure, or tissue inhomogeneities, the dose perturbation of the
      treatment couch top or immobilization devices is often overlooked. These devices
      also increase skin dose, an effect which is also often ignored or underestimated.
      These concerns have grown recently due to the increased use of monolithic carbon
      fiber couch tops which are optimal for imaging for patient position verification
      but cause attenuation and increased skin dose compared to the "tennis racket"
      style couch top they often replace. Also, arc delivery techniques have replaced
      stationary gantry techniques which cause a greater fraction of the dose to be
      delivered from posterior angles. A host of immobilization devices are available
      and used to increase patient positioning reproducibility, and these also have
      attenuation and skin dose implications which are often ignored. This report of
      Task Group 176 serves to present a survey of published data that illustrates the
      magnitude of the dosimetric effects of a wide range of devices external to the
      patient. The report also provides methods for modeling couch tops in treatment
      planning systems so the physicist can accurately compute the dosimetric effects
      for indexed patient treatments. Both photon and proton beams are considered. A
      discussion on avoidance of high density structures during beam planning is also
      provided. An important aspect of this report are the recommendations the authors
      make to clinical physicists, treatment planning system vendors, and device
      vendors on how to make measurements of surface dose and attenuation and how to
      report these values. For the vendors, an appeal is made to work together to
      provide accurate couch top models in planning systems. 

PMID- 24877796
TI  - Comparison of TG-43 and TG-186 in breast irradiation using a low energy
      electronic brachytherapy source.
AB  - PURPOSE: The recently updated guidelines for dosimetry in brachytherapy in TG-186
      have recommended the use of model-based dosimetry calculations as a replacement
      for TG-43. TG-186 highlights shortcomings in the water-based approach in TG-43,
      particularly for low energy brachytherapy sources. The Xoft Axxent is a low
      energy (<50 kV) brachytherapy system used in accelerated partial breast
      irradiation (APBI). Breast tissue is a heterogeneous tissue in terms of density
      and composition. Dosimetric calculations of seven APBI patients treated with
      Axxent were made using a model-based Monte Carlo platform for a number of tissue
      models and dose reporting methods and compared to TG-43 based plans. METHODS: A
      model of the Axxent source, the S700, was created and validated against
      experimental data. CT scans of the patients were used to create realistic multi
      tissue/heterogeneous models with breast tissue segmented using a published
      technique. Alternative water models were used to isolate the influence of tissue
      heterogeneity and backscatter on the dose distribution. Dose calculations were
      performed using Geant4 according to the original treatment parameters. The effect
      of the Axxent balloon applicator used in APBI which could not be modeled in the
      CT-based model, was modeled using a novel technique that utilizes CAD-based
      geometries. These techniques were validated experimentally. Results were
      calculated using two dose reporting methods, dose to water (Dw,m) and dose to
      medium (Dm,m), for the heterogeneous simulations. All results were compared
      against TG-43-based dose distributions and evaluated using dose ratio maps and
      DVH metrics. Changes in skin and PTV dose were highlighted. RESULTS: All
      simulated heterogeneous models showed a reduced dose to the DVH metrics that is
      dependent on the method of dose reporting and patient geometry. Based on a
      prescription dose of 34 Gy, the average D90 to PTV was reduced by between ~4% and
      ~40%, depending on the scoring method, compared to the TG-43 result. Peak skin
      dose is also reduced by 10%-15% due to the absence of backscatter not accounted
      for in TG-43. The balloon applicator also contributed to the reduced dose. Other
      ROIs showed a difference depending on the method of dose reporting. CONCLUSIONS:
      TG-186-based calculations produce results that are different from TG-43 for the
      Axxent source. The differences depend strongly on the method of dose reporting.
      This study highlights the importance of backscatter to peak skin dose. Tissue
      heterogeneities, applicator, and patient geometries demonstrate the need for a
      more robust dose calculation method for low energy brachytherapy sources.

PMID- 24877793
TI  - Synthetic zinc finger proteins: the advent of targeted gene regulation and genome
      modification technologies.
AB  - The understanding of gene regulation and the structure and function of the human
      genome increased dramatically at the end of the 20th century. Yet the
      technologies for manipulating the genome have been slower to develop. For
      instance, the field of gene therapy has been focused on correcting genetic
      diseases and augmenting tissue repair for more than 40 years. However, with the
      exception of a few very low efficiency approaches, conventional genetic
      engineering methods have only been able to add auxiliary genes to cells. This has
      been a substantial obstacle to the clinical success of gene therapies and has
      also led to severe unintended consequences in several cases. Therefore,
      technologies that facilitate the precise modification of cellular genomes have
      diverse and significant implications in many facets of research and are essential
      for translating the products of the Genomic Revolution into tangible benefits for
      medicine and biotechnology. To address this need, in the 1990s, we embarked on a
      mission to develop technologies for engineering protein-DNA interactions with the
      aim of creating custom tools capable of targeting any DNA sequence. Our goal has
      been to allow researchers to reach into genomes to specifically regulate, knock
      out, or replace any gene. To realize these goals, we initially focused on
      understanding and manipulating zinc finger proteins. In particular, we sought to
      create a simple and straightforward method that enables unspecialized
      laboratories to engineer custom DNA-modifying proteins using only defined modular
      components, a web-based utility, and standard recombinant DNA technology. Two
      significant challenges we faced were (i) the development of zinc finger domains
      that target sequences not recognized by naturally occurring zinc finger proteins
      and (ii) determining how individual zinc finger domains could be tethered
      together as polydactyl proteins to recognize unique locations within complex
      genomes. We and others have since used this modular assembly method to engineer
      artificial proteins and enzymes that activate, repress, or create defined changes
      to user-specified genes in human cells, plants, and other organisms. We have also
      engineered novel methods for externally controlling protein activity and
      delivery, as well as developed new strategies for the directed evolution of
      protein and enzyme function. This Account summarizes our work in these areas and
      highlights independent studies that have successfully used the modular assembly
      approach to create proteins with novel function. We also discuss emerging
      alternative methods for genomic targeting, including transcription activator-like
      effectors (TALEs) and CRISPR/Cas systems, and how they complement the synthetic
      zinc finger protein technology.

PMID- 24877797
TI  - The impact of cine EPID image acquisition frame rate on markerless soft-tissue
      tracking.
AB  - PURPOSE: Although reduction of the cine electronic portal imaging device (EPID)
      acquisition frame rate through multiple frame averaging may reduce hardware
      memory burden and decrease image noise, it can hinder the continuity of soft
      tissue motion leading to poor autotracking results. The impact of motion blurring
      and image noise on the tracking performance was investigated. METHODS: Phantom
      and patient images were acquired at a frame rate of 12.87 Hz with an amorphous
      silicon portal imager (AS1000, Varian Medical Systems, Palo Alto, CA). The
      maximum frame rate of 12.87 Hz is imposed by the EPID. Low frame rate images were
      obtained by continuous frame averaging. A previously validated tracking algorithm
      was employed for autotracking. The difference between the programmed and
      autotracked positions of a Las Vegas phantom moving in the superior-inferior
      direction defined the tracking error (delta). Motion blurring was assessed by
      measuring the area change of the circle with the greatest depth. Additionally,
      lung tumors on 1747 frames acquired at 11 field angles from four radiotherapy
      patients are manually and automatically tracked with varying frame averaging.
      delta was defined by the position difference of the two tracking methods. Image
      noise was defined as the standard deviation of the background intensity. Motion
      blurring and image noise are correlated with delta using Pearson correlation
      coefficient (R). RESULTS: For both phantom and patient studies, the autotracking
      errors increased at frame rates lower than 4.29 Hz. Above 4.29 Hz, changes in
      errors were negligible withdelta < 1.60 mm. Motion blurring and image noise were
      observed to increase and decrease with frame averaging, respectively. Motion
      blurring and tracking errors were significantly correlated for the phantom (R =
      0.94) and patient studies (R = 0.72). Moderate to poor correlation was found
      between image noise and tracking error with R -0.58 and -0.19 for both studies,
      respectively. CONCLUSIONS: Cine EPID image acquisition at the frame rate of at
      least 4.29 Hz is recommended. Motion blurring in the images with frame rates
      below 4.29 Hz can significantly reduce the accuracy of autotracking.

PMID- 24877798
TI  - Toward the development of intrafraction tumor deformation tracking using a
      dynamic multi-leaf collimator.
AB  - PURPOSE: Intrafraction deformation limits targeting accuracy in radiotherapy.
      Studies show tumor deformation of over 10 mm for both single tumor deformation
      and system deformation (due to differential motion between primary tumors and
      involved lymph nodes). Such deformation cannot be adapted to with current
      radiotherapy methods. The objective of this study was to develop and
      experimentally investigate the ability of a dynamic multi-leaf collimator (DMLC)
      tracking system to account for tumor deformation. METHODS: To compensate for
      tumor deformation, the DMLC tracking strategy is to warp the planned beam
      aperture directly to conform to the new tumor shape based on real time tumor
      deformation input. Two deformable phantoms that correspond to a single tumor and
      a tumor system were developed. The planar deformations derived from the phantom
      images in beam's eye view were used to guide the aperture warping. An in-house
      deformable image registration software was developed to automatically trigger the
      registration once new target image was acquired and send the computed deformation
      to the DMLC tracking software. Because the registration speed is not fast enough
      to implement the experiment in real-time manner, the phantom deformation only
      proceeded to the next position until registration of the current deformation
      position was completed. The deformation tracking accuracy was evaluated by a
      geometric target coverage metric defined as the sum of the area incorrectly
      outside and inside the ideal aperture. The individual contributions from the
      deformable registration algorithm and the finite leaf width to the tracking
      uncertainty were analyzed. Clinical proof-of-principle experiment of deformation
      tracking using previously acquired MR images of a lung cancer patient was
      implemented to represent the MRI-Linac environment. Intensity-modulated radiation
      therapy (IMRT) treatment delivered with enabled deformation tracking was
      simulated and demonstrated. RESULTS: The first experimental investigation of
      adapting to tumor deformation has been performed using simple deformable
      phantoms. For the single tumor deformation, the A(u)+A(o) was reduced over 56%
      when deformation was larger than 2 mm. Overall, the total improvement was 82%.
      For the tumor system deformation, the A(u)+A(o) reductions were all above 75% and
      the total A(u)+A(o) improvement was 86%. Similar coverage improvement was also
      found in simulating deformation tracking during IMRT delivery. The deformable
      image registration algorithm was identified as the dominant contributor to the
      tracking error rather than the finite leaf width. The discrepancy between the
      warped beam shape and the ideal beam shape due to the deformable registration was
      observed to be partially compensated during leaf fitting due to the finite leaf
      width. The clinical proof-of-principle experiment demonstrated the feasibility of
      intrafraction deformable tracking for clinical scenarios. CONCLUSIONS: For the
      first time, we developed and demonstrated an experimental system that is capable
      of adapting the MLC aperture to account for tumor deformation. This work provides
      a potentially widely available management method to effectively account for
      intrafractional tumor deformation. This proof-of-principle study is the first
      experimental step toward the development of an image-guided radiotherapy system
      to treat deforming tumors in real-time.

PMID- 24877800
TI  - Comparison of x ray computed tomography number to proton relative linear stopping
      power conversion functions using a standard phantom.
AB  - PURPOSE: Adequate evaluation of the results from multi-institutional trials
      involving light ion beam treatments requires consideration of the planning
      margins applied to both targets and organs at risk. A major uncertainty that
      affects the size of these margins is the conversion of x ray computed tomography
      numbers (XCTNs) to relative linear stopping powers (RLSPs). Various facilities
      engaged in multi-institutional clinical trials involving proton beams have been
      applying significantly different margins in their patient planning. This study
      was performed to determine the variance in the conversion functions used at
      proton facilities in the U.S.A. wishing to participate in National Cancer
      Institute sponsored clinical trials. METHODS: A simplified method of determining
      the conversion function was developed using a standard phantom containing only
      water and aluminum. The new method was based on the premise that all scanners
      have their XCTNs for air and water calibrated daily to constant values but that
      the XCTNs for high density/high atomic number materials are variable with
      different scanning conditions. The standard phantom was taken to 10 different
      proton facilities and scanned with the local protocols resulting in 14 derived
      conversion functions which were compared to the conversion functions used at the
      local facilities. RESULTS: For tissues within +/-300 XCTN of water, all facility
      functions produced converted RLSP values within +/-6% of the values produced by
      the standard function and within 8% of the values from any other facility's
      function. For XCTNs corresponding to lung tissue, converted RLSP values differed
      by as great as +/-8% from the standard and up to 16% from the values of other
      facilities. For XCTNs corresponding to low-density immobilization foam, the
      maximum to minimum values differed by as much as 40%. CONCLUSIONS: The new method
      greatly simplifies determination of the conversion function, reduces ambiguity,
      and in the future could promote standardization between facilities. Although it
      was not possible from these experiments to determine which conversion function is
      most appropriate, the variation between facilities suggests that the margins used
      in some facilities to account for the uncertainty in converting XCTNs to RLSPs
      may be too small.

PMID- 24877799
TI  - Motion as perturbation. II. Development of the method for dosimetric analysis of
      motion effects with fixed-gantry IMRT.
AB  - PURPOSE: In this work, the feasibility of implementing a motion-perturbation
      approach to accurately estimate volumetric dose in the presence of organ motion-
      previously demonstrated for VMAT--is studied for static gantry IMRT. The method's
      accuracy is improved for the voxels that have very low planned dose but acquire
      appreciable dose due to motion. The study describes the modified algorithm and
      its experimental validation and provides an example of a clinical application.
      METHODS: A contoured region-of-interest is propagated according to the predefined
      motion kernel throughout time-resolved 4D phantom dose grids. This timed series
      of 3D dose grids is produced by the measurement-guided dose reconstruction
      algorithm, based on an irradiation of a static ARCCHECK (AC) helical dosimeter
      array (Sun Nuclear Corp., Melbourne, FL). Each moving voxel collects dose over
      the dynamic simulation. The difference in dose-to-moving voxel vs dose-to-static
      voxel in-phantom forms the basis of a motion perturbation correction that is
      applied to the corresponding voxel in the patient dataset. A new method to
      synchronize the accelerator and dosimeter clocks, applicable to fixed-gantry
      IMRT, was developed. Refinements to the algorithm account for the excursion of
      low dose voxels into high dose regions, causing appreciable dose increase due to
      motion (LDVE correction). For experimental validation, four plans using TG-119
      structure sets and objectives were produced using segmented IMRT direct machine
      parameters optimization in Pinnacle treatment planning system (v. 9.6, Philips
      Radiation Oncology Systems, Fitchburg, WI). All beams were delivered with the
      gantry angle of 0 degrees . Each beam was delivered three times: (1) to the
      static AC centered on the room lasers; (2) to a static phantom containing a
      MAPCHECK2 (MC2) planar diode array dosimeter (Sun Nuclear); and (3) to the moving
      MC2 phantom. The motion trajectory was an ellipse in the IEC XY plane, with 3 and
      1.5 cm axes. The period was 5 s, with the resulting average motion speed of 1.45
      cm/s. The motion-perturbed high resolution (2 mm voxel) volumetric dose grids on
      the MC2 phantom were generated for each beam. From each grid, a coronal dose
      plane at the detector level was extracted and compared to the corresponding
      moving MC2 measurement, using gamma analysis with both global (G) and local (L)
      dose-error normalization. RESULTS: Using the TG-119 criteria of (3%G/3 mm), per
      beam average gamma analysis passing rates exceeded 95% in all cases. No
      individual beam had a passing rate below 91%. LDVE correction eliminated
      systematic disagreement patterns at the beams' aperture edges. In a
      representative example, application of LDVE correction improved (2%L/2 mm) gamma
      analysis passing rate for an IMRT beam from 74% to 98%. CONCLUSIONS: The effect
      of motion on the moving region-of-interest IMRT dose can be estimated with a
      standard, static phantom QA measurement, provided the motion characteristics are
      independently known from 4D CT or otherwise. The motion-perturbed absolute dose
      estimates were validated by the direct planar diode array measurements, and were
      found to reliably agree with them in a homogeneous phantom.

PMID- 24877801
TI  - Minibeam radiation therapy for the management of osteosarcomas: a Monte Carlo
      study.
AB  - PURPOSE: Minibeam radiation therapy (MBRT) exploits the well-established tissue
      sparing effect provided by the combination of submillimetric field sizes and a
      spatial fractionation of the dose. The aim of this work is to evaluate the
      feasibility and potential therapeutic gain of MBRT, in comparison with
      conventional radiotherapy, for osteosarcoma treatments. METHODS: Monte Carlo
      simulations (PENELOPE/penEasy code) were used as a method to study the dose
      distributions resulting from MBRT irradiations of a rat femur and a realistic
      human femur phantoms. As a figure of merit, peak and valley doses and peak-to
      valley dose ratios (PVDR) were assessed. Conversion of absorbed dose to
      normalized total dose (NTD) was performed in the human case. Several field sizes
      and irradiation geometries were evaluated. RESULTS: It is feasible to deliver a
      uniform dose distribution in the target while the healthy tissue benefits from a
      spatial fractionation of the dose. Very high PVDR values (?20) were achieved in
      the entrance beam path in the rat case. PVDR values ranged from 2 to 9 in the
      human phantom. NTD(2.0) of 87 Gy might be reached in the tumor in the human femur
      while the healthy tissues might receive valley NTD(2.0) lower than 20 Gy. The
      doses in the tumor and healthy tissues might be significantly higher and lower
      than the ones commonly delivered used in conventional radiotherapy. CONCLUSIONS:
      The obtained dose distributions indicate that a gain in normal tissue sparing
      might be expected. This would allow the use of higher (and potentially curative)
      doses in the tumor. Biological experiments are warranted.

PMID- 24877802
TI  - Magnetization curves of sintered heavy tungsten alloys for applications in MRI
      guided radiotherapy.
AB  - PURPOSE: Due to the current interest in MRI-guided radiotherapy, the magnetic
      properties of the materials commonly used in radiotherapy are becoming
      increasingly important. In this paper, measurement results for the magnetization
      (BH) curves of a range of sintered heavy tungsten alloys used in radiation
      shielding and collimation are presented. METHODS: Sintered heavy tungsten alloys
      typically contain >90% tungsten and <10% of a combination of iron, nickel, and
      copper binders. Samples of eight different grades of sintered heavy tungsten
      alloys with varying binder content were investigated. Using a superconducting
      quantum interference detector magnetometer, the induced magnetic moment m was
      measured for each sample as a function of applied external field H0 and the BH
      curve derived. RESULTS: The iron content of the alloys was found to play a
      dominant role, directly influencing the magnetization M and thus the nonlinearity
      of the BH curve. Generally, the saturation magnetization increased with
      increasing iron content of the alloy. Furthermore, no measurable magnetization
      was found for all alloys without iron content, despite containing up to 6% of
      nickel. For two samples from different manufacturers but with identical quoted
      nominal elemental composition (95% W, 3.5% Ni, 1.5% Fe), a relative difference in
      the magnetization of 11%-16% was measured. CONCLUSIONS: The measured curves show
      that the magnetic properties of sintered heavy tungsten alloys strongly depend on
      the iron content, whereas the addition of nickel in the absence of iron led to no
      measurable effect. Since a difference in the BH curves for two samples with
      identical quoted nominal composition from different manufacturers was observed,
      measuring of the BH curve for each individual batch of heavy tungsten alloys is
      advisable whenever accurate knowledge of the magnetic properties is crucial. The
      obtained BH curves can be used in FEM simulations to predict the magnetic impact
      of sintered heavy tungsten alloys.

PMID- 24877803
TI  - Absolute calibration of the Gamma Knife(r) PerfexionTM and delivered dose
      verification using EPR/alanine dosimetry.
AB  - PURPOSE: Elekta Leksell Gamma Knife((r)) (LGK) is a radiotherapy beam machine
      whose features are not compliant with the international calibration protocols for
      radiotherapy. In this scope, the Laboratoire National Henri Becquerel and the
      Pitie-Salpetriere Hospital decided to conceive a new LKG dose calibration method
      and to compare it with the currently used one. Furthermore, the accuracy of the
      dose delivered by the LGK machine was checked using an "end-to-end" test. This
      study also aims to compare doses delivered by the two latest software versions of
      the Gammaplan treatment planning system (TPS). METHODS: The dosimetric method
      chosen is the electron paramagnetic resonance (EPR) of alanine. Dose rate
      (calibration) verification was done without TPS using a spherical phantom.
      Absolute calibration was done with factors calculated by Monte Carlo simulation
      (MCNP-X). For "end-to-end" test, irradiations in an anthropomorphic head phantom,
      close to real treatment conditions, are done using the TPS in order to verify the
      delivered dose. RESULTS: The comparison of the currently used calibration method
      with the new one revealed a deviation of +0.8% between the dose rates measured by
      ion chamber and EPR/alanine. For simple fields configuration (less than 16 mm
      diameter), the "end-to-end" tests showed out average deviations of -1.7% and 
      0.9% between the measured dose and the calculated dose by Gammaplan v9 and v10,
      respectively. CONCLUSIONS: This paper shows there is a good agreement between the
      new calibration method and the currently used one. There is also a good agreement
      between the calculated and delivered doses especially for Gammaplan v10.

PMID- 24877804
TI  - A streamlined failure mode and effects analysis.
AB  - PURPOSE: Explore the feasibility and impact of a streamlined failure mode and
      effects analysis (FMEA) using a structured process that is designed to minimize
      staff effort. METHODS: FMEA for the external beam process was conducted at an
      affiliate radiation oncology center that treats approximately 60 patients per
      day. A structured FMEA process was developed which included clearly defined roles
      and goals for each phase. A core group of seven people was identified and a
      facilitator was chosen to lead the effort. Failure modes were identified and
      scored according to the FMEA formalism. A risk priority number,RPN, was
      calculated and used to rank failure modes. Failure modes with RPN > 150 received
      safety improvement interventions. Staff effort was carefully tracked throughout
      the project. RESULTS: Fifty-two failure modes were identified, 22 collected
      during meetings, and 30 from take-home worksheets. The four top-ranked failure
      modes were: delay in film check, missing pacemaker protocol/consent, critical
      structures not contoured, and pregnant patient simulated without the team's
      knowledge of the pregnancy. These four failure modes had RPN > 150 and received
      safety interventions. The FMEA was completed in one month in four 1-h meetings. A
      total of 55 staff hours were required and, additionally, 20 h by the facilitator.
      CONCLUSIONS: Streamlined FMEA provides a means of accomplishing a relatively
      large-scale analysis with modest effort. One potential value of FMEA is that it
      potentially provides a means of measuring the impact of quality improvement
      efforts through a reduction in risk scores. Future study of this possibility is
      needed.

PMID- 24877805
TI  - Pilot study for compact microbeam radiation therapy using a carbon nanotube field
      emission micro-CT scanner.
AB  - PURPOSE: Microbeam radiation therapy (MRT) is defined as the use of parallel,
      microplanar x-ray beams with an energy spectrum between 50 and 300 keV for cancer
      treatment and brain radiosurgery. Up until now, the possibilities of MRT have
      mainly been studied using synchrotron sources due to their high flux (100s Gy/s)
      and approximately parallel x-ray paths. The authors have proposed a compact x-ray
      based MRT system capable of delivering MRT dose distributions at a high dose
      rate. This system would employ carbon nanotube (CNT) field emission technology to
      create an x-ray source array that surrounds the target of irradiation. Using such
      a geometry, multiple collimators would shape the irradiation from this array into
      multiple microbeams that would then overlap or interlace in the target region.
      This pilot study demonstrates the feasibility of attaining a high dose rate and
      parallel microbeam beams using such a system. METHODS: The microbeam dose
      distribution was generated by our CNT micro-CT scanner (100 MUm focal spot) and a
      custom-made microbeam collimator. An alignment assembly was fabricated and
      attached to the scanner in order to collimate and superimpose beams coming from
      different gantry positions. The MRT dose distribution was measured using two
      orthogonal radiochromic films embedded inside a cylindrical phantom. This target
      was irradiated with microbeams incident from 44 different gantry angles to
      simulate an array of x-ray sources as in the proposed compact CNT-based MRT
      system. Finally, phantom translation in a direction perpendicular to the
      microplanar beams was used to simulate the use of multiple parallel microbeams.
      RESULTS: Microbeams delivered from 44 gantry angles were superimposed to form a
      single microbeam dose distribution in the phantom with a FWHM of 300 MUm
      (calculated value was 290 MUm). Also, during the multiple beam simulation, a peak
      to valley dose ratio of ~10 was found when the phantom translation distance was
      roughly 4x the beam width. The first prototype CNT-based x-ray tube dedicated to
      the development of compact MRT technology development was proposed and planned
      based on the preliminary experimental results presented here and the previous
      corresponding Monte Carlo simulations. CONCLUSIONS: The authors have demonstrated
      the feasibility of creating microbeam dose distributions at a high dose rate
      using a proposed compact MRT system. The flexibility of CNT field emission x-ray
      sources could possibly bring compact and low cost MRT devices to the larger
      research community and assist in the translational research of this promising new
      approach to radiation therapy.

PMID- 24877806
TI  - A DVH-guided IMRT optimization algorithm for automatic treatment planning and
      adaptive radiotherapy replanning.
AB  - PURPOSE: To develop a novel algorithm that incorporates prior treatment knowledge
      into intensity modulated radiation therapy optimization to facilitate automatic
      treatment planning and adaptive radiotherapy (ART) replanning. METHODS: The
      algorithm automatically creates a treatment plan guided by the DVH curves of a
      reference plan that contains information on the clinician-approved dose-volume
      trade-offs among different targets/organs and among different portions of a DVH
      curve for an organ. In ART, the reference plan is the initial plan for the same
      patient, while for automatic treatment planning the reference plan is selected
      from a library of clinically approved and delivered plans of previously treated
      patients with similar medical conditions and geometry. The proposed algorithm
      employs a voxel-based optimization model and navigates the large voxel-based
      Pareto surface. The voxel weights are iteratively adjusted to approach a plan
      that is similar to the reference plan in terms of the DVHs. If the reference plan
      is feasible but not Pareto optimal, the algorithm generates a Pareto optimal plan
      with the DVHs better than the reference ones. If the reference plan is too
      restricting for the new geometry, the algorithm generates a Pareto plan with DVHs
      close to the reference ones. In both cases, the new plans have similar DVH trade
      offs as the reference plans. RESULTS: The algorithm was tested using three
      patient cases and found to be able to automatically adjust the voxel-weighting
      factors in order to generate a Pareto plan with similar DVH trade-offs as the
      reference plan. The algorithm has also been implemented on a GPU for high
      efficiency. CONCLUSIONS: A novel prior-knowledge-based optimization algorithm has
      been developed that automatically adjust the voxel weights and generate a
      clinical optimal plan at high efficiency. It is found that the new algorithm can
      significantly improve the plan quality and planning efficiency in ART replanning
      and automatic treatment planning.

PMID- 24877807
TI  - Angular dependence of the response of the nanoDot OSLD system for measurements at
      depth in clinical megavoltage beams.
AB  - PURPOSE: The purpose of this investigation was to assess the angular dependence
      of a commercial optically stimulated luminescence dosimeter (OSLD) dosimetry
      system in MV x-ray beams at depths beyond d(max) and to find ways to mitigate
      this dependence for measurements in phantoms. METHODS: Two special holders were
      designed which allow a dosimeter to be rotated around the center of its sensitive
      volume. The dosimeter's sensitive volume is a disk, 5 mm in diameter and 0.2 mm
      thick. The first holder rotates the disk in the traditional way. It positions the
      disk perpendicular to the beam (gantry pointing to the floor) in the initial
      position (0 degrees ). When the holder is rotated the angle of the disk towards
      the beam increases until the disk is parallel with the beam ("edge on," 90
      degrees ). This is referred to as Setup 1. The second holder offers a new,
      alternative measurement position. It positions the disk parallel to the beam for
      all angles while rotating around its center (Setup 2). Measurements with five to
      ten dosimeters per point were carried out for 6 MV at 3 and 10 cm depth. Monte
      Carlo simulations using GEANT4 were performed to simulate the response of the
      active detector material for several angles. Detector and housing were simulated
      in detail based on microCT data and communications with the manufacturer. Various
      material compositions and an all-water geometry were considered. RESULTS: For the
      traditional Setup 1 the response of the OSLD dropped on average by 1.4% +/- 0.7%
      (measurement) and 2.1% +/- 0.3% (Monte Carlo simulation) for the 90 degrees 
      orientation compared to 0 degrees . Monte Carlo simulations also showed a strong
      dependence of the effect on the composition of the sensitive layer. Assuming the
      layer to completely consist of the active material (Al2O3) results in a 7% drop
      in response for 90 degrees  compared to 0 degrees . Assuming the layer to be
      completely water, results in a flat response within the simulation uncertainty of
      about 1%. For the new Setup 2, measurements and Monte Carlo simulations found the
      angular dependence of the dosimeter to be below 1% and within the measurement
      uncertainty. CONCLUSIONS: The dosimeter system exhibits a small angular
      dependence of approximately 2% which needs to be considered for measurements
      involving other than normal incident beams angles. This applies in particular to
      clinical in vivo measurements where the orientation of the dosimeter is dictated
      by clinical circumstances and cannot be optimized as otherwise suggested here.
      When measuring in a phantom, the proposed new setup should be considered. It
      changes the orientation of the dosimeter so that a coplanar beam arrangement
      always hits the disk shaped detector material from the thin side and thereby
      reduces the angular dependence of the response to within the measurement
      uncertainty of about 1%. This improvement makes the dosimeter more attractive for
      clinical measurements with multiple coplanar beams in phantoms, as the overall
      measurement uncertainty is reduced. Similarly, phantom based postal audits can
      transition from the traditional TLD to the more accurate and convenient OSLD.

PMID- 24877808
TI  - Optimizing mini-ridge filter thickness to reduce proton treatment times in a spot
      scanning synchrotron system.
AB  - PURPOSE: Study the contributors to treatment time as a function of Mini-Ridge
      Filter (MRF) thickness to determine the optimal choice for breath-hold treatment
      of lung tumors in a synchrotron-based spot-scanning proton machine. METHODS: Five
      different spot-scanning nozzles were simulated in TOPAS: four with MRFs of
      varying maximal thicknesses (6.15-24.6 mm) and one with no MRF. The MRFs were
      designed with ridges aligned along orthogonal directions transverse to the beam,
      with the number of ridges (4-16) increasing with MRF thickness. The material
      thickness given by these ridges approximately followed a Gaussian distribution.
      Using these simulations, Monte Carlo data were generated for treatment planning
      commissioning. For each nozzle, standard and stereotactic (SR) lung phantom
      treatment plans were created and assessed for delivery time and plan quality.
      RESULTS: Use of a MRF resulted in a reduction of the number of energy layers
      needed in treatment plans, decreasing the number of synchrotron spills needed and
      hence the treatment time. For standard plans, the treatment time per field
      without a MRF was 67.0 +/- 0.1 s, whereas three of the four MRF plans had
      treatment times of less than 20 s per field; considered sufficiently low for a
      single breath-hold. For SR plans, the shortest treatment time achieved was 57.7
      +/- 1.9 s per field, compared to 95.5 +/- 0.5 s without a MRF. There were
      diminishing gains in time reduction as the MRF thickness increased. Dose
      uniformity of the PTV was comparable across all plans; however, when the plans
      were normalized to have the same coverage, dose conformality decreased with MRF
      thickness, as measured by the lung V20%. CONCLUSIONS: Single breath-hold
      treatment times for plans with standard fractionation can be achieved through the
      use of a MRF, making this a viable option for motion mitigation in lung tumors.
      For stereotactic plans, while a MRF can reduce treatment times, multiple breath
      holds would still be necessary due to the limit imposed by the proton extraction
      time. To balance treatment time and normal tissue dose, the ideal MRF choice was
      shown to be the thinnest option that is able to achieve the desired breath-hold
      timing.

PMID- 24877809
TI  - Tissue decomposition from dual energy CT data for MC based dose calculation in
      particle therapy.
AB  - PURPOSE: The authors describe a novel method of predicting mass density and
      elemental mass fractions of tissues from dual energy CT (DECT) data for Monte
      Carlo (MC) based dose planning. METHODS: The relative electron density rho(e) and
      effective atomic number Z(eff) are calculated for 71 tabulated tissue
      compositions. For MC simulations, the mass density is derived via one linear fit
      in the rho(e) that covers the entire range of tissue compositions (except lung
      tissue). Elemental mass fractions are predicted from the rho(e) and the Z(eff) in
      combination. Since particle therapy dose planning and verification is especially
      sensitive to accurate material assignment, differences to the ground truth are
      further analyzed for mass density, I-value predictions, and stopping power ratios
      (SPR) for ions. Dose studies with monoenergetic proton and carbon ions in 12
      tissues which showed the largest differences of single energy CT (SECT) to DECT
      are presented with respect to range uncertainties. The standard approach (SECT)
      and the new DECT approach are compared to reference Bragg peak positions.
      RESULTS: Mean deviations to ground truth in mass density predictions could be
      reduced for soft tissue from (0.5+/-0.6)% (SECT) to (0.2+/-0.2)% with the DECT
      method. Maximum SPR deviations could be reduced significantly for soft tissue
      from 3.1% (SECT) to 0.7% (DECT) and for bone tissue from 0.8% to 0.1%. Mean I
      value deviations could be reduced for soft tissue from (1.1+/-1.4%, SECT) to
      (0.4+/-0.3%) with the presented method. Predictions of elemental composition were
      improved for every element. Mean and maximum deviations from ground truth of all
      elemental mass fractions could be reduced by at least a half with DECT compared
      to SECT (except soft tissue hydrogen and nitrogen where the reduction was
      slightly smaller). The carbon and oxygen mass fraction predictions profit
      especially from the DECT information. Dose studies showed that most of the 12
      selected tissues would profit significantly (up to 2.2%) from DECT material
      decomposition with no noise present. The rho(e) associated with an absolute noise
      of +/-0.01 and Z(eff) associated with an absolute noise of +/-0.2 resulted in +/
      10% standard variation in the carbon and oxygen mass fraction prediction.
      CONCLUSIONS: Accurate stopping power prediction is mainly determined by the
      correct mass density prediction. Theoretical improvements in range predictions
      with DECT data in the order of 0.1%-2.1% were observed. Further work is needed to
      quantify the potential improvements from DECT compared to SECT in measured image
      data associated with artifacts and noise.

PMID- 24877810
TI  - Delivery validation of an automated modulated electron radiotherapy plan.
AB  - PURPOSE: Modulated electron radiation therapy (MERT) represents an active area of
      interest that offers the potential to improve healthy tissue sparing in treatment
      of certain cancer cases. Challenges remain however in accurate beamlet dose
      calculation, plan optimization, collimation method, and delivery accuracy. In
      this work, the authors investigate the accuracy and efficiency of an end-to-end
      MERT plan and automated delivery method. METHODS: Treatment planning was
      initiated on a previously treated whole breast irradiation case including an
      electron boost. All dose calculations were performed using Monte Carlo methods
      and beam weights were determined using a research-based treatment planning system
      capable of inverse optimization. The plan was delivered to radiochromic film
      placed in a water equivalent phantom for verification, using an automated
      motorized tertiary collimator. RESULTS: The automated delivery, which covered
      four electron energies, 196 subfields, and 6183 total MU was completed in 25.8
      min, including 6.2 min of beam-on time. The remainder of the delivery time was
      spent on collimator leaf motion and the automated interfacing with the
      accelerator in service mode. Comparison of the planned and delivered film dose
      gave 3%/3mm gamma pass rates of 62.1%, 99.8%, 97.8%, 98.3%, and 98.7% for the 9,
      12, 16, and 20 MeV, and combined energy deliveries, respectively. Delivery was
      also performed with a MapCHECK device and resulted in 3%/3 mm gamma pass rates of
      88.8%, 86.1%, 89.4%, and 94.8% for the 9, 12, 16, and 20 MeV energies,
      respectively. CONCLUSIONS: Results of the authors' study showed that an accurate
      delivery utilizing an add-on tertiary electron collimator is possible using Monte
      Carlo calculated plans and inverse optimization, which brings MERT closer to
      becoming a viable option for physicians in treating superficial malignancies.

PMID- 24877811
TI  - Dosimetric adaptive IMRT driven by fiducial points.
AB  - PURPOSE: Intensity modulated radiotherapy (IMRT) and volumetric modulated arc
      therapy have become standard treatments but are more sensitive to anatomical
      variations than 3D conformal techniques. To correct for inter- and intrafraction
      anatomical variations, fast and easy to implement methods are needed. Here, the
      authors propose a full dosimetric IMRT correction that finds a compromise in
      between basic repositioning (the current clinical practice) and full replanning.
      It simplifies replanning by avoiding a recontouring step and a full dose
      calculation. It surpasses repositioning by updating the preoptimized fluence and
      monitor units (MU) using a limited number of fiducial points and a pretreatment
      (CB)CT. To adapt the fluence the fiducial points were projected in the beam's eye
      view (BEV). To adapt the MUs, point dose calculation towards the same fiducial
      points were performed. The proposed method is intrinsically fast and robust, and
      simple to understand for operators, because of the use of only four fiducial
      points and the beam data based point dose calculations. METHODS: To perform our
      dosimetric adaptation, two fluence corrections in the BEV are combined with two
      MU correction steps along the beam's path. (1) A transformation of the fluence
      map such that it is realigned with the current target geometry. (2) A correction
      for an unintended scaling of the penumbra margin when the treatment beams scale
      to the current target size. (3) A correction for the target depth relative to the
      body contour and (4) a correction for the target distance to the source. The
      impact of the correction strategy and its individual components was evaluated by
      simulations on a virtual prostate phantom. This heterogeneous reference phantom
      was systematically subjected to population based prostate transformations to
      simulate interfraction variations. Additionally, a patient example illustrated
      the clinical practice. The correction strategy was evaluated using both
      dosimetric (CTV mean dose, conformity index) and clinical (tumor control
      probability, and normal tissue complication probability) measures. RESULTS: Based
      on the current experiments, the intended target dose and tumor control
      probability could be assured by the proposed method (TCP >= TCP(intended)).
      Additionally, the conformity index error was more than halved compared to the
      current clinical practice (DeltaCI(95%) from 40% to 16%) resulting in improved
      organ at risk protection. All the individual correction steps had an added value
      to the full correction. CONCLUSIONS: A limited number of fiducial points (no
      organ contours required) and an in-room (CB)CT are sufficient to perform a full
      dosimetric correction for IMRT plans. In the presence of interfraction variation,
      the corrected plans show superior dose distributions compared to our current
      clinical practice.

PMID- 24877812
TI  - Characterization of scatter in digital mammography from physical measurements.
AB  - PURPOSE: That scattered radiation negatively impacts the quality of medical
      radiographic imaging is well known. In mammography, even slight amounts of
      scatter reduce the high contrast required for subtle soft-tissue imaging. In
      current clinical mammography, image contrast is partially improved by use of an
      antiscatter grid. This form of scatter rejection comes with a sizeable dose
      penalty related to the concomitant elimination of valuable primary radiation.
      Digital mammography allows the use of image processing as a method of scatter
      correction that might avoid effects that negatively impact primary radiation,
      while potentially providing more contrast improvement than is currently possible
      with a grid. For this approach to be feasible, a detailed characterization of the
      scatter is needed. Previous research has modeled scatter as a constant background
      that serves as a DC bias across the imaging surface. The goal of this study was
      to provide a more substantive data set for characterizing the spatially-variant
      features of scatter radiation at the image detector of modern mammography units.
      METHODS: This data set was acquired from a model of the radiation beam as a
      matrix of very narrow rays or pencil beams. As each pencil beam penetrates
      tissue, the pencil widens in a predictable manner due to the production of
      scatter. The resultant spreading of the pencil beam at the detector surface can
      be characterized by two parameters: mean radial extent (MRE) and scatter fraction
      (SF). The SF and MRE were calculated from measurements obtained using the beam
      stop method. Two digital mammography units were utilized, and the SF and MRE were
      found as functions of target, filter, tube potential, phantom thickness, and
      presence or absence of a grid. These values were then used to generate general
      equations allowing the SF and MRE to be calculated for any combination of the
      above parameters. RESULTS: With a grid, the SF ranged from a minimum of about
      0.05 to a maximum of about 0.16, and the MRE ranged from about 3 to 13 mm.
      Without a grid, the SF ranged from a minimum of 0.25 to a maximum of 0.52, and
      the MRE ranged from about 20 to 45 mm. The SF with a grid demonstrated a mild
      dependence on target/filter combination and kV, whereas the SF without a grid was
      independent of these factors. The MRE demonstrated a complex relationship as a
      function of kV, with notable difference among target/filter combinations. The
      primary source of change in both the SF and MRE was phantom thickness.
      CONCLUSIONS: Because breast tissue varies spatially in physical density and
      elemental content, the effective thickness of breast tissue varies spatially
      across the imaging field, resulting in a spatially-variant scatter distribution
      in the imaging field. The data generated in this study can be used to
      characterize the scatter contribution on a point-by-point basis, for a variety of
      different techniques.

PMID- 24877814
TI  - Feature-space assessment of electrical impedance tomography coregistered with
      computed tomography in detecting multiple contrast targets.
AB  - PURPOSE: Fusion of electrical impedance tomography (EIT) with computed tomography
      (CT) can be useful as a clinical tool for providing additional physiological
      information about tissues, but requires suitable fusion algorithms and validation
      procedures. This work explores the feasibility of fusing EIT and CT images using
      an algorithm for coregistration. The imaging performance is validated through
      feature space assessment on phantom contrast targets. METHODS: EIT data were
      acquired by scanning a phantom using a circuit, configured for injecting current
      through 16 electrodes, placed around the phantom. A conductivity image of the
      phantom was obtained from the data using electrical impedance and diffuse optical
      tomography reconstruction software (EIDORS). A CT image of the phantom was also
      acquired. The EIT and CT images were fused using a region of interest (ROI)
      coregistration fusion algorithm. Phantom imaging experiments were carried out on
      objects of different contrasts, sizes, and positions. The conductive medium of
      the phantoms was made of a tissue-mimicking bolus material that is routinely used
      in clinical radiation therapy settings. To validate the imaging performance in
      detecting different contrasts, the ROI of the phantom was filled with distilled
      water and normal saline. Spatially separated cylindrical objects of different
      sizes were used for validating the imaging performance in multiple target
      detection. Analyses of the CT, EIT and the EIT/CT phantom images were carried out
      based on the variations of contrast, correlation, energy, and homogeneity, using
      a gray level co-occurrence matrix (GLCM). A reference image of the phantom was
      simulated using EIDORS, and the performances of the CT and EIT imaging systems
      were evaluated and compared against the performance of the EIT/CT system using
      various feature metrics, detectability, and structural similarity index measures.
      RESULTS: In detecting distilled and normal saline water in bolus medium, EIT as a
      stand-alone imaging system showed contrast discrimination of 47%, while the CT
      imaging system showed a discrimination of only 1.5%. The structural similarity
      index measure showed a drop of 24% with EIT imaging compared to CT imaging. The
      average detectability measure for CT imaging was found to be 2.375 +/- 0.19
      before fusion. After complementing with EIT information, the detectability
      measure increased to 11.06 +/- 2.04. Based on the feature metrics, the functional
      imaging quality of CT and EIT were found to be 2.29% and 86%, respectively,
      before fusion. Structural imaging quality was found to be 66% for CT and 16% for
      EIT. After fusion, functional imaging quality improved in CT imaging from 2.29%
      to 42% and the structural imaging quality of EIT imaging changed from 16% to 66%.
      The improvement in image quality was also observed in detecting objects of
      different sizes. CONCLUSIONS: The authors found a significant improvement in the
      contrast detectability performance of CT imaging when complemented with
      functional imaging information from EIT. Along with the feature assessment
      metrics, the concept of complementing CT with EIT imaging can lead to an EIT/CT
      imaging modality which might fully utilize the functional imaging abilities of
      EIT imaging, thereby enhancing the quality of care in the areas of cancer
      diagnosis and radiotherapy treatment planning.

PMID- 24877813
TI  - Fiducial marker-based correction for involuntary motion in weight-bearing C-arm
      CT scanning of knees. II. Experiment.
AB  - PURPOSE: A C-arm CT system has been shown to be capable of scanning a single
      cadaver leg under loaded conditions by virtue of its highly flexible acquisition
      trajectories. In Part I of this study, using the 4D XCAT-based numerical
      simulation, the authors predicted that the involuntary motion in the lower body
      of subjects in weight-bearing positions would seriously degrade image quality and
      the authors suggested three motion compensation methods by which the
      reconstructions could be corrected to provide diagnostic image quality. Here, the
      authors demonstrate that a flat-panel angiography system is appropriate for
      scanning both legs of subjects in vivo under weight-bearing conditions and
      further evaluate the three motion-correction algorithms using in vivo data.
      METHODS: The geometry of a C-arm CT system for a horizontal scan trajectory was
      calibrated using the PDS-2 phantom. The authors acquired images of two healthy
      volunteers while lying supine on a table, standing, and squatting at several knee
      flexion angles. In order to identify the involuntary motion of the lower body,
      nine 1-mm-diameter tantalum fiducial markers were attached around the knee. The
      static mean marker position in 3D, a reference for motion compensation, was
      estimated by back-projecting detected markers in multiple projections using
      calibrated projection matrices and identifying the intersection points in 3D of
      the back-projected rays. Motion was corrected using three different methods
      (described in detail previously): (1) 2D projection shifting, (2) 2D deformable
      projection warping, and (3) 3D rigid body warping. For quantitative image quality
      analysis, SSIM indices for the three methods were compared using the supine data
      as a ground truth. RESULTS: A 2D Euclidean distance-based metric of subjects'
      motion ranged from 0.85 mm (+/-0.49 mm) to 3.82 mm (+/-2.91 mm) (corresponding to
      2.76 to 12.41 pixels) resulting in severe motion artifacts in 3D reconstructions.
      Shifting in 2D, 2D warping, and 3D warping improved the SSIM in the central slice
      by 20.22%, 16.83%, and 25.77% in the data with the largest motion among the five
      datasets (SCAN5); improvement in off-center slices was 18.94%, 29.14%, and
      36.08%, respectively. CONCLUSIONS: The authors showed that C-arm CT control can
      be implemented for nonstandard horizontal trajectories which enabled us to scan
      and successfully reconstruct both legs of volunteers in weight-bearing positions.
      As predicted using theoretical models, the proposed motion correction methods
      improved image quality by reducing motion artifacts in reconstructions; 3D
      warping performed better than the 2D methods, especially in off-center slices.

PMID- 24877815
TI  - Measurement of cardiac output from dynamic pulmonary circulation time CT.
AB  - PURPOSE: To introduce a method of estimating cardiac output from the dynamic
      pulmonary circulation time CT that is primarily used to determine the optimal
      time window of CT pulmonary angiography (CTPA). METHODS: Dynamic pulmonary
      circulation time CT series, acquired for eight patients, were retrospectively
      analyzed. The dynamic CT series was acquired, prior to the main CTPA, in cine
      mode (1 frame/s) for a single slice at the level of the main pulmonary artery
      covering the cross sections of ascending aorta (AA) and descending aorta (DA)
      during the infusion of iodinated contrast. The time series of contrast changes
      obtained for DA, which is the downstream of AA, was assumed to be related to the
      time series for AA by the convolution with a delay function. The delay time
      constant in the delay function, representing the average time interval between
      the cross sections of AA and DA, was determined by least square error fitting
      between the convoluted AA time series and the DA time series. The cardiac output
      was then calculated by dividing the volume of the aortic arch between the cross
      sections of AA and DA (estimated from the single slice CT image) by the average
      time interval, and multiplying the result by a correction factor. RESULTS: The
      mean cardiac output value for the six patients was 5.11 (l/min) (with a standard
      deviation of 1.57 l/min), which is in good agreement with the literature value;
      the data for the other two patients were too noisy for processing. CONCLUSIONS:
      The dynamic single-slice pulmonary circulation time CT series also can be used to
      estimate cardiac output.

PMID- 24877816
TI  - Learning directional relative positions between mediastinal lymph node stations
      and organs.
AB  - PURPOSE: To automatically learn directional relative positions (DRP) between
      mediastinal lymph node stations and anatomical organs. Those spatial
      relationships are used to semiautomatically segment the stations in thoracic CT
      images. METHODS: Fuzzy maps of DRP were automatically extracted by a learning
      procedure from a database composed of images with stations and anatomical
      structures manually segmented by consensus between experts. Spatial relationships
      common to all patients were retained. The segmentation of a new image used an
      initial rough delineation of anatomical organs and applied the DRP operators. The
      algorithm was tested with a leave-one-out approach on a database of 5 patients
      with 10 lymph stations and 30 anatomical structures each. Results were compared
      to expert delineations with dice similarity coefficient (DSC) and bidirectional
      local distance (BLD). RESULTS: The overall mean DSC was 66% and the mean BLD was
      1.7 mm. Best matches were obtained from stations S3P or S4R while lower matches
      were obtained for stations 1R and 1L. On average, more than 30 spatial
      relationships were automatically extracted for each station. CONCLUSIONS: This
      feasibility study suggests that mediastinal lymph node stations could be
      satisfactory segmented from thoracic CT using automatically extracted positional
      relationships with anatomical organs. This approach requires the anatomical
      structures to be initially roughly delineated. A similar approach could be
      applied to other sites where spatial relationships exists between anatomical
      structures. The complete database of the five reference cases is made publicly
      available.

PMID- 24877817
TI  - Upright cone beam CT imaging using the onboard imager.
AB  - PURPOSE: Many patients could benefit from being treated in an upright position.
      The objectives of this study were to determine whether cone beam computed
      tomography (CBCT) could be used to acquire upright images for treatment planning
      and to demonstrate whether reconstruction of upright images maintained accurate
      geometry and Hounsfield units (HUs). METHODS: A TrueBeam linac was programmed in
      developer mode to take upright CBCT images. The gantry head was positioned at 0
      degrees , and the couch was rotated to 270 degrees . The x-ray source and
      detector arms were extended to their lateral positions. The x-ray source and
      gantry remained stationary as fluoroscopic projections were taken and the couch
      was rotated from 270 degrees  to 90 degrees . The x-ray tube current was
      normalized to deposit the same dose (measured using a calibrated Farmer ion
      chamber) as that received during a clinical helical CT scan to the center of a
      cylindrical, polyethylene phantom. To extend the field of view, two couch
      rotation scans were taken with the detector offset 15 cm superiorly and then 15
      cm inferiorly. The images from these two scans were stitched together before
      reconstruction. Upright reconstructions were compared to reconstructions from
      simulation CT scans of the same phantoms. Two methods were investigated for
      correcting the HUs, including direct calibration and mapping the values from a
      simulation CT. RESULTS: Overall geometry, spatial linearity, and high contrast
      resolution were maintained in upright reconstructions. Some artifacts were
      created and HU accuracy was compromised; however, these limitations could be
      removed by mapping the HUs from a simulation CT to the upright reconstruction for
      treatment planning. CONCLUSIONS: The feasibility of using the TrueBeam linac to
      take upright CBCT images was demonstrated. This technique is straightforward to
      implement and could be of enormous benefit to patients with thoracic tumors or
      those who find a supine position difficult to endure.

PMID- 24877818
TI  - Control algorithms for dynamic attenuators.
AB  - PURPOSE: The authors describe algorithms to control dynamic attenuators in CT and
      compare their performance using simulated scans. Dynamic attenuators are
      prepatient beam shaping filters that modulate the distribution of x-ray fluence
      incident on the patient on a view-by-view basis. These attenuators can reduce
      dose while improving key image quality metrics such as peak or mean variance. In
      each view, the attenuator presents several degrees of freedom which may be
      individually adjusted. The total number of degrees of freedom across all views is
      very large, making many optimization techniques impractical. The authors develop
      a theory for optimally controlling these attenuators. Special attention is paid
      to a theoretically perfect attenuator which controls the fluence for each ray
      individually, but the authors also investigate and compare three other, practical
      attenuator designs which have been previously proposed: the piecewise-linear
      attenuator, the translating attenuator, and the double wedge attenuator. METHODS:
      The authors pose and solve the optimization problems of minimizing the mean and
      peak variance subject to a fixed dose limit. For a perfect attenuator and mean
      variance minimization, this problem can be solved in simple, closed form. For
      other attenuator designs, the problem can be decomposed into separate problems
      for each view to greatly reduce the computational complexity. Peak variance
      minimization can be approximately solved using iterated, weighted mean variance
      (WMV) minimization. Also, the authors develop heuristics for the perfect and
      piecewise-linear attenuators which do not require a priori knowledge of the
      patient anatomy. The authors compare these control algorithms on different types
      of dynamic attenuators using simulated raw data from forward projected DICOM
      files of a thorax and an abdomen. RESULTS: The translating and double wedge
      attenuators reduce dose by an average of 30% relative to current techniques
      (bowtie filter with tube current modulation) without increasing peak variance.
      The 15-element piecewise-linear dynamic attenuator reduces dose by an average of
      42%, and the perfect attenuator reduces dose by an average of 50%. Improvements
      in peak variance are several times larger than improvements in mean variance.
      Heuristic control eliminates the need for a prescan. For the piecewise-linear
      attenuator, the cost of heuristic control is an increase in dose of 9%. The
      proposed iterated WMV minimization produces results that are within a few percent
      of the true solution. CONCLUSIONS: Dynamic attenuators show potential for
      significant dose reduction. A wide class of dynamic attenuators can be accurately
      controlled using the described methods.

PMID- 24877819
TI  - Task-based strategy for optimized contrast enhanced breast imaging: analysis of
      six imaging techniques for mammography and tomosynthesis.
AB  - PURPOSE: The use of contrast agents in breast imaging has the capability of
      enhancing nodule detectability and providing physiological information.
      Accordingly, there has been a growing trend toward using iodine as a contrast
      medium in digital mammography (DM) and digital breast tomosynthesis (DBT).
      Widespread use raises concerns about the best way to use iodine in DM and DBT,
      and thus a comparison is necessary to evaluate typical iodine-enhanced imaging
      methods. This study used a task-based observer model to determine the optimal
      imaging approach by analyzing six imaging paradigms in terms of their ability to
      resolve iodine at a given dose: unsubtracted mammography and tomosynthesis,
      temporal subtraction mammography and tomosynthesis, and dual energy subtraction
      mammography and tomosynthesis. METHODS: Imaging performance was characterized
      using a detectability index d', derived from the system task transfer function
      (TTF), an imaging task, iodine signal difference, and the noise power spectrum
      (NPS). The task modeled a 10 mm diameter lesion containing iodine concentrations
      between 2.1 mg/cc and 8.6 mg/cc. TTF was obtained using an edge phantom, and the
      NPS was measured over several exposure levels, energies, and target-filter
      combinations. Using a structured CIRS phantom, d' was generated as a function of
      dose and iodine concentration. RESULTS: For all iodine concentrations and dose,
      temporal subtraction techniques for mammography and tomosynthesis yielded the
      highest d', while dual energy techniques for both modalities demonstrated the
      next best performance. Unsubtracted imaging resulted in the lowest d' values for
      both modalities, with unsubtracted mammography performing the worst out of all
      six paradigms. CONCLUSIONS: At any dose, temporal subtraction imaging provides
      the greatest detectability, with temporally subtracted DBT performing the
      highest. The authors attribute the successful performance to excellent
      cancellation of inplane structures and improved signal difference in the lesion.

PMID- 24877820
TI  - Noise, sampling, and the number of projections in cone-beam CT with a flat-panel
      detector.
AB  - PURPOSE: To investigate the effect of the number of projection views on image
      noise in cone-beam CT (CBCT) with a flat-panel detector. METHODS: This fairly
      fundamental consideration in CBCT system design and operation was addressed
      experimentally (using a phantom presenting a uniform medium as well as
      statistically motivated "clutter") and theoretically (using a cascaded systems
      model describing CBCT noise) to elucidate the contributing factors of quantum
      noise (sigma(Q)), electronic noise (sigma(E)), and view aliasing (sigma(view)).
      Analysis included investigation of the noise, noise-power spectrum, and
      modulation transfer function as a function of the number of projections
      (N(proj)), dose (D(tot)), and voxel size (b(vox)). RESULTS: The results reveal a
      nonmonotonic relationship between image noise and N(proj) at fixed total dose:
      for the CBCT system considered, noise decreased with increasing N(proj) due to
      reduction of view sampling effects in the regime N(proj) <~200, above which noise
      increased with N(proj) due to increased electronic noise. View sampling effects
      were shown to depend on the heterogeneity of the object in a direct analytical
      relationship to power-law anatomical clutter of the form kappa/f(beta)--and a
      general model of individual noise components (sigma(Q), sigma(E), and
      sigma(view)) demonstrated agreement with measurements over a broad range in
      N(proj), D(tot), and b(vox). CONCLUSIONS: The work elucidates fairly basic
      elements of CBCT noise in a manner that demonstrates the role of distinct noise
      components (viz., quantum, electronic, and view sampling noise). For
      configurations fairly typical of CBCT with a flat-panel detector (FPD), the
      analysis reveals a "sweet spot" (i.e., minimum noise) in the range N(proj) ~ 250
      350, nearly an order of magnitude lower in N(proj) than typical of multidetector
      CT, owing to the relatively high electronic noise in FPDs. The analysis
      explicitly relates view aliasing and quantum noise in a manner that includes
      aspects of the object ("clutter") and imaging chain (including nonidealities of
      detector blur and electronic noise) to provide a more rigorous basis for commonly
      held intuition and heurism in CBCT system design and operation.

PMID- 24877821
TI  - Improved image quality of cone beam CT scans for radiotherapy image guidance
      using fiber-interspaced antiscatter grid.
AB  - PURPOSE: Medical linear accelerator mounted cone beam CT (CBCT) scanner provides
      useful soft tissue contrast for purposes of image guidance in radiotherapy. The
      presence of extensive scattered radiation has a negative effect on soft tissue
      visibility and uniformity of CBCT scans. Antiscatter grids (ASG) are used in the
      field of diagnostic radiography to mitigate the scatter. They usually do increase
      the contrast of the scan, but simultaneously increase the noise. Therefore, and
      considering other scatter mitigation mechanisms present in a CBCT scanner, the
      applicability of ASGs with aluminum interspacing for a wide range of imaging
      conditions has been inconclusive in previous studies. In recent years, grids
      using fiber interspacers have appeared, providing grids with higher scatter
      rejection while maintaining reasonable transmission of primary radiation. The
      purpose of this study was to evaluate the impact of one such grid on CBCT image
      quality. METHODS: The grid used (Philips Medical Systems) had ratio of 21:1,
      frequency 36 lp/cm, and nominal selectivity of 11.9. It was mounted on the kV
      flat panel detector of an Elekta Synergy linear accelerator and tested in a
      phantom and a clinical study. Due to the flex of the linac and presence of
      gridline artifacts an angle dependent gain correction algorithm was devised to
      mitigate resulting artifacts. Scan reconstruction was performed using XVI4.5
      augmented with inhouse developed image lag correction and Hounsfield unit
      calibration. To determine the necessary parameters for Hounsfield unit
      calibration and software scatter correction parameters, the Catphan 600 (The
      Phantom Laboratory) phantom was used. Image quality parameters were evaluated
      using CIRS CBCT Image Quality and Electron Density Phantom (CIRS) in two
      different geometries: one modeling head and neck and other pelvic region.
      Phantoms were acquired with and without the grid and reconstructed with and
      without software correction which was adapted for the different acquisition
      scenarios. Parameters used in the phantom study were t(cup) for nonuniformity and
      contrast-to-noise ratio (CNR) for soft tissue visibility. Clinical scans were
      evaluated in an observer study in which four experienced radiotherapy
      technologists rated soft tissue visibility and uniformity of scans with and
      without the grid. RESULTS: The proposed angle dependent gain correction algorithm
      suppressed the visible ring artifacts. Grid had a beneficial impact on
      nonuniformity, contrast to noise ratio, and Hounsfield unit accuracy for both
      scanning geometries. The nonuniformity reduced by 90% for head sized object and
      91% for pelvic-sized object. CNR improved compared to no corrections on average
      by a factor 2.8 for the head sized object, and 2.2 for the pelvic sized phantom.
      Grid outperformed software correction alone, but adding additional software
      correction to the grid was overall the best strategy. In the observer study, a
      significant improvement was found in both soft tissue visibility and
      nonuniformity of scans when grid is used. CONCLUSIONS: The evaluated fiber
      interspaced grid improved the image quality of the CBCT system for broad range of
      imaging conditions. Clinical scans show significant improvement in soft tissue
      visibility and uniformity without the need to increase the imaging dose.

PMID- 24877823
TI  - Imaging dose in variable pitch body perfusion CT scans: an analysis using TG111
      formalism.
AB  - PURPOSE: To investigate the variation of imaging dose with tube potential in
      variable pitch body CT perfusion (CTp) protocols using the TG111 dosimetric
      formalism. METHODS: TG111 recommendations were followed in choosing the phantom,
      dosimetric equipment, and methodology. Specifically, equilibrium doses (D(eq))
      were measured centrally and peripherally in a long PMMA phantom. Reference planar
      average equilibrium doses were determined for each tube potential, for a
      reference set of exposure parameters (collimation, pitch, filtration) on a
      Siemens Definition CT scanner. These reference values were utilized to predict
      the imaging dose during perfusion scans using interpretations of the TG111
      formalism. As a gold reference, the midscan average planar perfusion doses
      (D(CTp)) were obtained directly from central and peripheral D(eq) measurements
      for body CTp scans (144 and 271 mm) using variable pitch acquisition. Measurement
      based D(CTp) values obtained using a thimble chamber were compared to the TG111
      predicted values, and to CTDI(vol) reported at the console. RESULTS: Reference
      planar average equilibrium dose values measured for reference uniform pitch
      helical scans were consistently higher than console-reported or measured values
      for CTDI(vol). The measurement-based perfusion dose D(CTp) was predicted
      accurately by the reported CTDI(vol) for the 144 mm scan. The 271 mm scans
      delivered systematically larger dose than reported. The TG111-based dose
      estimates were proven to be conservative, as they were systematically higher than
      both the measured and the reported imaging doses. CONCLUSIONS: Upon successful
      implementation of TG111 formalism, standard imaging dose was measured for a body
      CTp protocol using the variable pitch helical acquisition. The TG111 formalism is
      not directly applicable to this type of acquisition. Measurement of dose for all
      variable pitch protocols is strongly suggested.

PMID- 24877822
TI  - Improved digital breast tomosynthesis images using automated ultrasound.
AB  - PURPOSE: Digital breast tomosynthesis (DBT) offers poor image quality along the
      depth direction. This paper presents a new method that improves the image quality
      of DBT considerably through the a priori information from automated ultrasound
      (AUS) images. METHODS: DBT and AUS images of a complex breast-mimicking phantom
      are acquired by a DBT/AUS dual-modality system. The AUS images are taken in the
      same geometry as the DBT images and the gradient information of the in-slice AUS
      images is adopted into the new loss functional during the DBT reconstruction
      process. The additional data allow for new iterative equations through solving
      the optimization problem utilizing the gradient descent method. Both visual
      comparison and quantitative analysis are employed to evaluate the improvement on
      DBT images. Normalized line profiles of lesions are obtained to compare the edges
      of the DBT and AUS-corrected DBT images. Additionally, image quality metrics such
      as signal difference to noise ratio (SDNR) and artifact spread function (ASF) are
      calculated to quantify the effectiveness of the proposed method. RESULTS: In
      traditional DBT image reconstructions, serious artifacts can be found along the
      depth direction (Z direction), resulting in the blurring of lesion edges in the
      off-focus planes parallel to the detector. However, by applying the proposed
      method, the quality of the reconstructed DBT images is greatly improved.
      Visually, the AUS-corrected DBT images have much clearer borders in both in-focus
      and off-focus planes, fewer Z direction artifacts and reduced overlapping effect
      compared to the conventional DBT images. Quantitatively, the corrected DBT images
      have better ASF, indicating a great reduction in Z direction artifacts as well as
      better Z resolution. The sharper line profiles along the Y direction show
      enhancement on the edges. Besides, noise is also reduced, evidenced by the
      obviously improved SDNR values. CONCLUSIONS: The proposed method provides great
      improvement on the quality of DBT images. This improvement makes it easier to
      locate and to distinguish a lesion, which may help improve the accuracy of the
      diagnosis using DBT imaging.

PMID- 24877824
TI  - A bronchoscopic navigation system using bronchoscope center calibration for
      accurate registration of electromagnetic tracker and CT volume without markers.
AB  - PURPOSE: Various bronchoscopic navigation systems are developed for diagnosis,
      staging, and treatment of lung and bronchus cancers. To construct
      electromagnetically navigated bronchoscopy systems, registration of preoperative
      images and an electromagnetic tracker must be performed. This paper proposes a
      new marker-free registration method, which uses the centerlines of the bronchial
      tree and the center of a bronchoscope tip where an electromagnetic sensor is
      attached, to align preoperative images and electromagnetic tracker systems.
      METHODS: The chest computed tomography (CT) volume (preoperative images) was
      segmented to extract the bronchial centerlines. An electromagnetic sensor was
      fixed at the bronchoscope tip surface. A model was designed and printed using a
      3D printer to calibrate the relationship between the fixed sensor and the
      bronchoscope tip center. For each sensor measurement that includes sensor
      position and orientation information, its corresponding bronchoscope tip center
      position was calculated. By minimizing the distance between each bronchoscope tip
      center position and the bronchial centerlines, the spatial alignment of the
      electromagnetic tracker system and the CT volume was determined. After obtaining
      the spatial alignment, an electromagnetic navigation bronchoscopy system was
      established to real-timely track or locate a bronchoscope inside the bronchial
      tree during bronchoscopic examinations. RESULTS: The electromagnetic navigation
      bronchoscopy system was validated on a dynamic bronchial phantom that can
      simulate respiratory motion with a breath rate range of 0-10 min(-1). The
      fiducial and target registration errors of this navigation system were evaluated.
      The average fiducial registration error was reduced from 8.7 to 6.6 mm. The
      average target registration error, which indicates all tracked or navigated
      bronchoscope position accuracy, was much reduced from 6.8 to 4.5 mm compared to
      previous registration methods. CONCLUSIONS: An electromagnetically navigated
      bronchoscopy system was constructed with accurate registration of an
      electromagnetic tracker and the CT volume on the basis of an improved marker-free
      registration approach that uses the bronchial centerlines and bronchoscope tip
      center information. The fiducial and target registration errors of our
      electromagnetic navigation system were about 6.6 and 4.5 mm in dynamic bronchial
      phantom validation.

PMID- 24877825
TI  - Alpha image reconstruction (AIR): a new iterative CT image reconstruction
      approach using voxel-wise alpha blending.
AB  - PURPOSE: Iterative image reconstruction gains more and more interest in clinical
      routine, as it promises to reduce image noise (and thereby patient dose), to
      reduce artifacts, or to improve spatial resolution. Among vendors and
      researchers, however, there is no consensus of how to best achieve these aims.
      The general approach is to incorporate a priori knowledge into iterative image
      reconstruction, for example, by adding additional constraints to the cost
      function, which penalize variations between neighboring voxels. However, this
      approach to regularization in general poses a resolution noise trade-off because
      the stronger the regularization, and thus the noise reduction, the stronger the
      loss of spatial resolution and thus loss of anatomical detail. The authors
      propose a method which tries to improve this trade-off. The proposed
      reconstruction algorithm is called alpha image reconstruction (AIR). One starts
      with generating basis images, which emphasize certain desired image properties,
      like high resolution or low noise. The AIR algorithm reconstructs voxel-specific
      weighting coefficients that are applied to combine the basis images. By combining
      the desired properties of each basis image, one can generate an image with lower
      noise and maintained high contrast resolution thus improving the resolution noise
      trade-off. METHODS: All simulations and reconstructions are performed in native
      fan-beam geometry. A water phantom with resolution bar patterns and low contrast
      disks is simulated. A filtered backprojection (FBP) reconstruction with a Ram-Lak
      kernel is used as a reference reconstruction. The results of AIR are compared
      against the FBP results and against a penalized weighted least squares
      reconstruction which uses total variation as regularization. The simulations are
      based on the geometry of the Siemens Somatom Definition Flash scanner. To
      quantitatively assess image quality, the authors analyze line profiles through
      resolution patterns to define a contrast factor for contrast-resolution plots.
      Furthermore, the authors calculate the contrast-to-noise ratio with the low
      contrast disks and the authors compare the agreement of the reconstructions with
      the ground truth by calculating the normalized cross-correlation and the root
      mean-square deviation. To evaluate the clinical performance of the proposed
      method, the authors reconstruct patient data acquired with a Somatom Definition
      Flash dual source CT scanner (Siemens Healthcare, Forchheim, Germany). RESULTS:
      The results of the simulation study show that among the compared algorithms AIR
      achieves the highest resolution and the highest agreement with the ground truth.
      Compared to the reference FBP reconstruction AIR is able to reduce the relative
      pixel noise by up to 50% and at the same time achieve a higher resolution by
      maintaining the edge information from the basis images. These results can be
      confirmed with the patient data. CONCLUSIONS: To evaluate the AIR algorithm
      simulated and measured patient data of a state-of-the-art clinical CT system were
      processed. It is shown, that generating CT images through the reconstruction of
      weighting coefficients has the potential to improve the resolution noise trade
      off and thus to improve the dose usage in clinical CT.

PMID- 24877826
TI  - Interior micro-CT with an offset detector.
AB  - PURPOSE: The size of field-of-view (FOV) of a microcomputed tomography (CT)
      system can be increased by offsetting the detector. The increased FOV is
      beneficial in many applications. All prior investigations, however, have been
      focused to the case in which the increased FOV after offset-detector acquisition
      can cover the transaxial extent of an object fully. Here, the authors studied a
      new problem where the FOV of a micro-CT system, although increased after offset
      detector acquisition, still covers an interior region-of-interest (ROI) within
      the object. METHODS: An interior-ROI-oriented micro-CT scan with an offset
      detector poses a difficult reconstruction problem, which is caused by both
      detector offset and projection truncation. Using the projection completion
      techniques, the authors first extended three previous reconstruction methods from
      offset-detector micro-CT to offset-detector interior micro-CT. The authors then
      proposed a novel method which combines two of the extended methods using a
      frequency split technique. The authors tested the four methods with phantom
      simulations at 9.4%, 18.8%, 28.2%, and 37.6% detector offset. The authors also
      applied these methods to physical phantom datasets acquired at the same amounts
      of detector offset from a customized micro-CT system. RESULTS: When the detector
      offset was small, all reconstruction methods showed good image quality. At large
      detector offset, the three extended methods gave either visible shading artifacts
      or high deviation of pixel value, while the authors' proposed method demonstrated
      no visible artifacts and minimal deviation of pixel value in both the numerical
      simulations and physical experiments. CONCLUSIONS: For an interior micro-CT with
      an offset detector, the three extended reconstruction methods can perform well at
      a small detector offset but show strong artifacts at a large detector offset.
      When the detector offset is large, the authors' proposed reconstruction method
      can outperform the three extended reconstruction methods by suppressing artifacts
      and maintaining pixel values.

PMID- 24877828
TI  - A method for multichannel dosimetry with EBT3 radiochromic films.
AB  - PURPOSE: An improved method for multichannel dosimetry is presented. This method
      explicitly takes into account the information provided by the unexposed image of
      the film. METHODS: The method calculates the dose by applying a couple of
      perturbations to the scanned dose, one dependent and the other independent on the
      color channel. The method has been compared with previous multichannel and two
      single channel methods (red and green) against measurements using two different
      tests: first, five percentage depth dose profiles covering a wide range of doses;
      second, the dose map perpendicular to the beam axis for a 15 * 15 cm(2) square
      field. Finally, the results of 30 IMRT quality assurances tests are presented.
      All tests have been evaluated using the gamma analysis. RESULTS: The coefficient
      of variation was found to be similar for all methods in a wide range of doses.
      The results of the proposed method are more in agreement with the experimental
      measurements and with the treatment planning system. Furthermore, the differences
      in the mean gamma pass rates are statistically significant. CONCLUSIONS: The
      improved multichannel dosimetric method is able to remove many of the common
      disturbances usually present in radiochromic films and improves the gamma
      analysis results compared with the other three methods.

PMID- 24877827
TI  - Optimization of the design of thick, segmented scintillators for megavoltage cone
      beam CT using a novel, hybrid modeling technique.
AB  - PURPOSE: Active matrix flat-panel imagers (AMFPIs) incorporating thick, segmented
      scintillators have demonstrated order-of-magnitude improvements in detective
      quantum efficiency (DQE) at radiotherapy energies compared to systems based on
      conventional phosphor screens. Such improved DQE values facilitate megavoltage
      cone-beam CT (MV CBCT) imaging at clinically practical doses. However, the MV
      CBCT performance of such AMFPIs is highly dependent on the design parameters of
      the scintillators. In this paper, optimization of the design of segmented
      scintillators was explored using a hybrid modeling technique which encompasses
      both radiation and optical effects. METHODS: Imaging performance in terms of the
      contrast-to-noise ratio (CNR) and spatial resolution of various hypothetical
      scintillator designs was examined through a hybrid technique involving Monte
      Carlo simulation of radiation transport in combination with simulation of optical
      gain distributions and optical point spread functions. The optical simulations
      employed optical parameters extracted from a best fit to measurement results
      reported in a previous investigation of a 1.13 cm thick, 1016 MUm pitch prototype
      BGO segmented scintillator. All hypothetical designs employed BGO material with a
      thickness and element-to-element pitch ranging from 0.5 to 6 cm and from 0.508 to
      1.524 mm, respectively. In the CNR study, for each design, full tomographic scans
      of a contrast phantom incorporating various soft-tissue inserts were simulated at
      a total dose of 4 cGy. RESULTS: Theoretical values for contrast, noise, and CNR
      were found to be in close agreement with empirical results from the BGO
      prototype, strongly supporting the validity of the modeling technique. CNR and
      spatial resolution for the various scintillator designs demonstrate complex
      behavior as scintillator thickness and element pitch are varied--with a clear
      trade-off between these two imaging metrics up to a thickness of ~3 cm. Based on
      these results, an optimization map indicating the regions of design that provide
      a balance between these metrics was obtained. The map shows that, for a given set
      of optical parameters, scintillator thickness and pixel pitch can be judiciously
      chosen to maximize performance without resorting to thicker, more costly
      scintillators. CONCLUSIONS: Modeling radiation and optical effects in thick,
      segmented scintillators through use of a hybrid technique can provide a practical
      way to gain insight as to how to optimize the performance of such devices in
      radiotherapy imaging. Assisted by such modeling, the development of practical
      designs should greatly facilitate low-dose, soft tissue visualization employing
      MV CBCT imaging in external beam radiotherapy.

PMID- 24877830
TI  - Quasi real time in vivo dosimetry for VMAT.
AB  - PURPOSE: Results about the feasibility of a method for quasi real time in vivo
      dosimetry (IVD) at the isocenter point for volumetric modulated arc therapy
      (VMAT) are here reported. The method is based on correlations between the EPID
      signal and the dose on the beam central axis. Moreover, the gamma-analysis of
      EPID images was adopted to verify off-axis reproducibility of fractionated plan
      delivery. METHODS: An algorithm to reconstruct in vivo the isocenter dose,
      D(iso), for RapidArc treatments has been developed. 20 VMAT plans, optimized with
      two opposite arcs, for prostate, pancreas, and head treatments have been
      delivered by a Varian linac both to a conic PMMA phantom with elliptical section
      and to patients. The ratios R between reconstructed D(iso) and the planned doses
      were determined for phantom and patient irradiations adopting an acceptance
      criterion of +/-5%. In total, 40 phantom checks and 400 patient checks were
      analyzed. Moreover, 3% and 3 mm criteria were adopted for portal image gamma
      analysis to assess patient irradiation reproducibility. RESULTS: The average
      ratio R, between reconstructed and planned doses for the PMMA phantom
      irradiations was equal to 1.007 +/- 0.024. When the IVD method was applied to the
      20 patients, the average R ratio was equal to 1.003 +/- 0.017 and 96% of the
      tests were within the acceptance criteria. The portal image gamma-analysis
      supplied 88% of the tests within the pass rates gamma(mean) <= 0.4 and P(gamma<1)
      >= 98%. All the warnings were understood comparing the CT and the cone beam CT
      images and in one case a patient's setup error was detected and corrected for the
      successive fractions. CONCLUSIONS: This preliminary experience suggests that the
      method is able to detect dosimetric errors in quasi real time at the end of the
      therapy session. The authors intend to extend this procedure to other pathologies
      with the integration of in-room imaging verification by cone beam CT.

PMID- 24877829
TI  - Video-rate optical dosimetry and dynamic visualization of IMRT and VMAT treatment
      plans in water using Cherenkov radiation.
AB  - PURPOSE: A novel technique for optical dosimetry of dynamic intensity-modulated
      radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) plans was
      investigated for the first time by capturing images of the induced Cherenkov
      radiation in water. METHODS: A high-sensitivity, intensified CCD camera (ICCD)
      was configured to acquire a two-dimensional (2D) projection image of the
      Cherenkov radiation induced by IMRT and VMAT plans, based on the Task Group 119
      (TG-119) C-Shape geometry. Plans were generated using the Varian Eclipse
      treatment planning system (TPS) and delivered using 6 MV x-rays from a Varian
      TrueBeam Linear Accelerator (Linac) incident on a water tank doped with the
      fluorophore quinine sulfate. The ICCD acquisition was gated to the Linac target
      trigger pulse to reduce background light artifacts, read out for a single
      radiation pulse, and binned to a resolution of 512 * 512 pixels. The resulting
      videos were analyzed temporally for various regions of interest (ROI) covering
      the planning target volume (PTV) and organ at risk (OAR), and summed to obtain an
      overall light intensity distribution, which was compared to the expected dose
      distribution from the TPS using a gamma-index analysis. RESULTS: The chosen
      camera settings resulted in 23.5 frames per second dosimetry videos. Temporal
      intensity plots of the PTV and OAR ROIs confirmed the preferential delivery of
      dose to the PTV versus the OAR, and the gamma analysis yielded 95.9% and 96.2%
      agreement between the experimentally captured Cherenkov light distribution and
      expected TPS dose distribution based upon a 3%/3 mm dose difference and distance
      to-agreement criterion for the IMRT and VMAT plans, respectively. CONCLUSIONS:
      The results from this initial study demonstrate the first documented use of
      Cherenkov radiation for video-rate optical dosimetry of dynamic IMRT and VMAT
      treatment plans. The proposed modality has several potential advantages over
      alternative methods including the real-time nature of the acquisition, and upon
      future refinement may prove to be a robust and novel dosimetry method with both
      research and clinical applications.

PMID- 24877831
TI  - An angle-dependent estimation of CT x-ray spectrum from rotational transmission
      measurements.
AB  - PURPOSE: Computed tomography (CT) performance as well as dose and image quality
      is directly affected by the x-ray spectrum. However, the current assessment
      approaches of the CT x-ray spectrum require costly measurement equipment and
      complicated operational procedures, and are often limited to the spectrum
      corresponding to the center of rotation. In order to address these limitations,
      the authors propose an angle-dependent estimation technique, where the incident
      spectra across a wide range of angular trajectories can be estimated accurately
      with only a single phantom and a single axial scan in the absence of the
      knowledge of the bowtie filter. METHODS: The proposed technique uses a uniform
      cylindrical phantom, made of ultra-high-molecular-weight polyethylene and
      positioned in an off-centered geometry. The projection data acquired with an
      axial scan have a twofold purpose. First, they serve as a reflection of the
      transmission measurements across different angular trajectories. Second, they are
      used to reconstruct the cross sectional image of the phantom, which is then
      utilized to compute the intersection length of each transmission measurement.
      With each CT detector element recording a range of transmission measurements for
      a single angular trajectory, the spectrum is estimated for that trajectory. A
      data conditioning procedure is used to combine information from hundreds of
      collected transmission measurements to accelerate the estimation speed, to reduce
      noise, and to improve estimation stability. The proposed spectral estimation
      technique was validated experimentally using a clinical scanner (Somatom
      Definition Flash, Siemens Healthcare, Germany) with spectra provided by the
      manufacturer serving as the comparison standard. Results obtained with the
      proposed technique were compared against those obtained from a second
      conventional transmission measurement technique with two materials (i.e., Cu and
      Al). After validation, the proposed technique was applied to measure spectra from
      the clinical system across a range of angular trajectories [-15 degrees , 15
      degrees ] and spectrum settings (80, 100, 120, 140 kVp). RESULTS: At 140 kVp, the
      proposed technique was comparable to the conventional technique in terms of the
      mean energy difference (MED, -0.29 keV) and the normalized root mean square
      difference (NRMSD, 0.84%) from the comparison standard compared to 0.64 keV and
      1.56%, respectively, with the conventional technique. The average absolute MEDs
      and NRMSDs across kVp settings and angular trajectories were less than 0.61 keV
      and 3.41%, respectively, which indicates a high level of estimation accuracy and
      stability. CONCLUSIONS: An angle-dependent estimation technique of CT x-ray
      spectra from rotational transmission measurements was proposed. Compared with the
      conventional technique, the proposed method simplifies the measurement procedures
      and enables incident spectral estimation for a wide range of angular
      trajectories. The proposed technique is suitable for rigorous research objectives
      as well as routine clinical quality control procedures.

PMID- 24877832
TI  - Characterization of calibration curves and energy dependence GafChromicTM XR-QA2
      model based radiochromic film dosimetry system.
AB  - PURPOSE: The authors investigated the energy response of XR-QA2 GafChromicTM film
      over a broad energy range used in diagnostic radiology examinations. The authors
      also made an assessment of the most suitable functions for both reference and
      relative dose measurements. METHODS: Pieces of XR-QA2 film were irradiated to
      nine different values of air kerma in air, following reference calibration of a
      number of beam qualities ranging in HVLs from 0.16 to 8.25 mm Al, which
      corresponds to effective energy range from 12.7 keV to 56.3 keV. For each beam
      quality, the authors tested three functional forms (rational, linear exponential,
      and power) to assess the most suitable function by fitting the delivered air
      kerma in air as a function of film response in terms of reflectance change. The
      authors also introduced and tested a new parameter chi = netDeltaR.e(m netDeltaR)
      that linearizes the inherently nonlinear response of the film. RESULTS: The
      authors have found that in the energy range investigated, the response of the XR
      QA2 based radiochromic film dosimetry system ranges from 0.222 to 0.420 in terms
      of netDeltaR at K(air)(air) = 8 cGy. For beam qualities commonly used in CT
      scanners (4.03-8.25 mm Al), the variation in film response (netDeltaR at
      K(air)(air) = 8 cGy) amounts to +/- 5%, while variation in K(air)(air) amounts to
      +/- 14%. CONCLUSIONS: Results of our investigation revealed that the use of XR
      QA2 GafChromicTM film is accompanied by a rather pronounced energy dependent
      response for beam qualities used for x-ray based diagnostic imaging purposes. The
      authors also found that the most appropriate function for the reference
      radiochromic film dosimetry would be the power function, while for the relative
      dosimetry one may use the exponential response function that can be easily
      linearized.

PMID- 24877833
TI  - Magnetic resonance visualization of conductive structures by sequence-triggered
      direct currents and spin-echo phase imaging.
AB  - PURPOSE: Instrument visualization in interventional magnetic resonance imaging
      (MRI) is commonly performed via susceptibility artifacts. Unfortunately, this
      approach suffers from limited conspicuity in inhomogeneous tissue and disturbed
      spatial encoding. Also, susceptibility artifacts are controllable only by
      sequence parameters. This work presents the basics of a new visualization method
      overcoming such problems by applying sequence-triggered direct current (DC)
      pulses in spin-echo (SE) imaging. SE phase images allow for background free
      current path localization. METHODS: Application of a sequence-triggered DC pulse
      in SE imaging, e.g., during a time period between radiofrequency excitation and
      refocusing, results in transient field inhomogeneities. Dependent on the
      additional z-magnetic field from the DC, a phase offset results despite the
      refocusing pulse. False spatial encoding is avoided by DC application during
      periods when read-out or slice-encoding gradients are inactive. A water phantom
      containing a brass conductor (water equivalent susceptibility) and a titanium
      needle (serving as susceptibility source) was used to demonstrate the
      feasibility. Artifact dependence on current strength and orientation was
      examined. RESULTS: Without DC, the brass conductor was only visible due to its
      water displacement. The titanium needle showed typical susceptibility artifacts.
      Applying triggered DC pulses, the phase offset of spins near the conductor
      appeared. Because SE phase images are homogenous also in regions of persistent
      field inhomogeneities, the position of the conductor could be determined with
      high reliability. Artifact characteristic could be easily controlled by amperage
      leaving sequence parameters unchanged. For an angle of 30 degrees  between
      current and static field visualization was still possible. CONCLUSIONS: SE phase
      images display the position of a conductor carrying pulsed DC free from artifacts
      caused by persistent field inhomogeneities. Magnitude and phase images are
      acquired simultaneously under the same conditions without the use of extra
      measurement time. The presented technique offers many advantages for precise
      instrument localization in interventional MRI.

PMID- 24877834
TI  - View-sharing PROPELLER with pixel-based optimal blade selection: application on
      dynamic contrast-enhanced imaging.
AB  - PURPOSE: To achieve better spatial and temporal resolution of dynamic contrast
      enhanced MR imaging, the concept of k-space data sharing, or view sharing, can be
      implemented for PROPELLER acquisition. As found in other view-sharing methods,
      the loss of high-resolution dynamics is possible for view-sharing PROPELLER (VS
      Prop) due to the temporal smoothing effect. The degradation can be more severe
      when a narrow blade with less phase encoding steps is chosen in the acquisition
      for higher frame rate. In this study, an iterative algorithm termed pixel-based
      optimal blade selection (POBS) is proposed to allow spatially dependent selection
      of the rotating blades, to generate high-resolution dynamic images with minimal
      reconstruction artifacts. METHODS: In the reconstruction of VS-Prop, the central
      k-space which dominates the image contrast is only provided by the target blade
      with the peripheral k-space contributed by a minimal number of consecutive
      rotating blades. To reduce the reconstruction artifacts, the set of neighboring
      blades exhibiting the closest image contrast with the target blade is picked by
      POBS algorithm. Numerical simulations and phantom experiments were conducted in
      this study to investigate the dynamic response and spatial profiles of images
      generated using our proposed method. In addition, dynamic contrast-enhanced
      cardiovascular imaging of healthy subjects was performed to demonstrate the
      feasibility and advantages. RESULTS: The simulation results show that POBS VS
      Prop can provide timely dynamic response to rapid signal change, especially for a
      small region of interest or with the use of narrow blades. The POBS algorithm
      also demonstrates its capability to capture nonsimultaneous signal changes over
      the entire FOV. In addition, both phantom and in vivo experiments show that the
      temporal smoothing effect can be avoided by means of POBS, leading to higher wash
      in slope of contrast enhancement after the bolus injection. CONCLUSIONS: With the
      satisfactory reconstruction quality provided by the POBS algorithm, VS-Prop
      acquisition technique may find useful clinical applications in DCE MR imaging
      studies where both spatial and temporal resolutions play important roles.

PMID- 24877835
TI  - Experimental evaluation and basis function optimization of the spatially variant
      image-space PSF on the Ingenuity PET/MR scanner.
AB  - PURPOSE: The Ingenuity time-of-flight (TF) PET/MR is a recently developed hybrid
      scanner combining the molecular imaging capabilities of PET with the excellent
      soft tissue contrast of MRI. It is becoming common practice to characterize the
      system's point spread function (PSF) and understand its variation under spatial
      transformations to guide clinical studies and potentially use it within
      resolution recovery image reconstruction algorithms. Furthermore, due to the
      system's utilization of overlapping and spherical symmetric Kaiser-Bessel basis
      functions during image reconstruction, its image space PSF and reconstructed
      spatial resolution could be affected by the selection of the basis function
      parameters. Hence, a detailed investigation into the multidimensional basis
      function parameter space is needed to evaluate the impact of these parameters on
      spatial resolution. METHODS: Using an array of 12 * 7 printed point sources,
      along with a custom made phantom, and with the MR magnet on, the system's
      spatially variant image-based PSF was characterized in detail. Moreover, basis
      function parameters were systematically varied during reconstruction (list-mode
      TF OSEM) to evaluate their impact on the reconstructed resolution and the image
      space PSF. Following the spatial resolution optimization, phantom, and clinical
      studies were subsequently reconstructed using representative basis function
      parameters. RESULTS: Based on the analysis and under standard basis function
      parameters, the axial and tangential components of the PSF were found to be
      almost invariant under spatial transformations (~4 mm) while the radial component
      varied modestly from 4 to 6.7 mm. Using a systematic investigation into the basis
      function parameter space, the spatial resolution was found to degrade for basis
      functions with a large radius and small shape parameter. However, it was found
      that optimizing the spatial resolution in the reconstructed PET images, while
      having a good basis function superposition and keeping the image representation
      error to a minimum, is feasible, with the parameter combination range depending
      upon the scanner's intrinsic resolution characteristics. CONCLUSIONS: Using the
      printed point source array as a MR compatible methodology for experimentally
      measuring the scanner's PSF, the system's spatially variant resolution properties
      were successfully evaluated in image space. Overall the PET subsystem exhibits
      excellent resolution characteristics mainly due to the fact that the raw data are
      not under-sampled/rebinned, enabling the spatial resolution to be dictated by the
      scanner's intrinsic resolution and the image reconstruction parameters. Due to
      the impact of these parameters on the resolution properties of the reconstructed
      images, the image space PSF varies both under spatial transformations and due to
      basis function parameter selection. Nonetheless, for a range of basis function
      parameters, the image space PSF remains unaffected, with the range depending on
      the scanner's intrinsic resolution properties.

PMID- 24877836
TI  - Effect of time-of-flight and point spread function modeling on detectability of
      myocardial defects in PET.
AB  - PURPOSE: A study was designed to investigate the impact of time-of-flight (TOF)
      and point spread function (PSF) modeling on the detectability of myocardial
      defects. METHODS: Clinical FDG-PET data were used to generate populations of
      defect-present and defect-absent images. Defects were incorporated at three
      contrast levels, and images were reconstructed by ordered subset expectation
      maximization (OSEM) iterative methods including ordinary Poisson, alone and with
      PSF, TOF, and PSF+TOF. Channelized Hotelling observer signal-to-noise ratio (SNR)
      was the surrogate for human observer performance. RESULTS: For three iterations,
      12 subsets, and no postreconstruction smoothing, TOF improved overall defect
      detection SNR by 8.6% as compared to its non-TOF counterpart for all the defect
      contrasts. Due to the slow convergence of PSF reconstruction, PSF yielded 4.4%
      less SNR than non-PSF. For reconstruction parameters (iteration number and
      postreconstruction smoothing kernel size) optimizing observer SNR, PSF showed
      larger improvement for faint defects. The combination of TOF and PSF improved
      mean detection SNR as compared to non-TOF and non-PSF counterparts by 3.0% and
      3.2%, respectively. CONCLUSIONS: For typical reconstruction protocol used in
      clinical practice, i.e., less than five iterations, TOF improved defect
      detectability. In contrast, PSF generally yielded less detectability. For large
      number of iterations, TOF+PSF yields the best observer performance.

PMID- 24877837
TI  - On the dose calculation at the cellular level and its implications for the RBE of
      (99m)Tc and 123I.
AB  - PURPOSE: Based on the authors' previous findings concerning the radiotoxicity
      of(99m)Tc, the authors compared the cellular survival under the influence of this
      nuclide with that following exposure to the Auger electron emitter (123)I. To
      evaluate the relative biological effectiveness (RBE) of both radionuclides,
      knowledge of the absorbed dose is essential. Thus, the authors present the dose
      calculations and discuss the results based on different models of the
      radionuclide distribution. Both different target volumes and the influence of the
      uptake kinetics were considered. METHODS: Rat thyroid PC Cl3 cells in culture
      were incubated with either(99m)Tc or (123)I or were irradiated using 200 kV x
      rays in the presence or absence of perchlorate. The clonogenic cell survival was
      measured via colony formation. In addition, the intracellular radionuclide uptake
      was quantified. Single-cell dose calculations were based on Monte Carlo
      simulations performed using Geant4. RESULTS: Compared with external radiation
      using x-rays (D37 = 2.6 Gy), the radionuclides (99m)Tc (D37 = 3.5 Gy), and (123)I
      (D37 = 3.8 Gy) were less toxic in the presence of perchlorate. In the absence of
      perchlorate, the amount of activity a37 that was necessary to reduce the
      surviving fraction (SF) to 0.37 was 22.8 times lower for (99m)Tc and 12.4 times
      lower for (123)I because of the dose increase caused by intracellular
      radionuclide accumulation. When the cell nucleus was considered as the target for
      the dose calculation, the authors found a RBE of 2.18 for (99m)Tc and RBE = 3.43
      for (123)I. Meanwhile, regarding the dose to the entire cell, RBE = 0.75 for
      (99m)Tc and RBE = 1.87 for (123)I. The dose to the entire cell was chosen as the
      dose criterion because of the intracellular radionuclide accumulation, which was
      found to occur solely in the cytoplasm. The calculated number of intracellular
      decays per cell was (975 +/- 109) decays/MBq for (99m)Tc and (221 +/- 82)
      decays/MBq for (123)I. CONCLUSIONS: The authors' data indicate that extra-nuclear
      targets to Auger electrons exist, which is obvious from our dose calculations.
      When considering the dose to the cell nucleus, the authors found an enhanced RBE
      for(99m)Tc and (123)I relative to acute x-ray irradiation and pure extracellular
      irradiation with both radionuclides. Surprisingly, the authors did not find any
      radionuclide accumulation in the cell nucleus, indicating that there are
      additional radiosensitive targets besides the DNA. In addition, the authors
      demonstrated the necessity of cellular dose calculations in radiobiological
      experiments using unsealed radionuclides and identified the relevant parameters.

PMID- 24877838
TI  - Focused ultrasound treatment of abscesses induced by methicillin resistant
      Staphylococcus aureus: feasibility study in a mouse model.
AB  - PURPOSE: To study the therapeutic effect of focused ultrasound on abscesses
      induced by methicillin-resistant Staphylococcus aureus (MRSA). MRSA is a major
      nosocomial pathogen where immunocompromised patients are prone to develop
      infections that are less and less responsive to regular treatments. Because of
      its capability to induce a rise of temperature at a very precise location, the
      use of focused ultrasound represents a considerable opportunity for therapy of
      localized MRSA-related infections. METHODS: 50 MUl of MRSA strain USA400 bacteria
      suspension at a concentration of 1.32 +/- 0.5 * 10(5) colony forming units
      (cfu)/MUl was injected subcutaneously in the left flank of BALB/c mice. An
      abscess of 6 +/- 2 mm in diameter formed after 48 h. A transducer operating at 3
      MHz with a focal length of 50 mm and diameter of 32 mm was used to treat the
      abscess. The focal point was positioned 2 mm under the skin at the abscess
      center. Forty-eight hours after injection four ultrasound exposures of 9 s each
      were applied to each abscess under magnetic resonance imaging guidance. Each
      exposure was followed by a 1 min pause. These parameters were based on
      preliminary experiments to ensure repetitive accurate heating of the abscess.
      Real-time estimation of change of temperature was done using water-proton
      resonance frequency and a communication toolbox (matMRI) developed inhouse. Three
      experimental groups of animals each were tested: control, moderate temperature
      (MT), and high temperature (HT). MT and HT groups reached, respectively, 52.3 +/-
      5.1 and 63.8 +/- 7.5  degrees C at the end of exposure. Effectiveness of the
      treatment was assessed by evaluating the bacteria amount of the treated abscess 1
      and 4 days after treatment. Myeloperoxidase (MPO) assay evaluating the neutrophil
      amount was performed to assess the local neutrophil recruitment and the white
      blood cell count was used to evaluate the systemic inflammatory response after
      focused ultrasound treatment. RESULTS: Macroscopic evaluation of treated abscess
      indicated a diminution of external size of abscess 1 day after treatment.
      Treatment did not cause open wounds. The median (lower to upper quartile)
      bacterial count 1 day after treatment was 6.18 * 10(3) (0.76 * 10(3)-11.18 *
      10(3)), 2.86 * 10(3) (1.22 * 10(3)-7.07 * 10(3)), and 3.52 * 10(3) (1.18 * 10(3)
      6.72 * 10(3)) cfu/100 MUl for control, MT and HT groups, respectively; for the 4
      day end point, the count was 1.37 * 10(3) (0.67 * 10(3)-2.89 * 10(3)), 1.35 *
      10(3) (0.09 * 10(3)-2.96 * 10(3)), and 0.07 * 10(3) (0.03 * 10(3)-0.36 * 10(3))
      cfu/100 MUl for control, MT and HT, showing a significant reduction (p = 0.002)
      on the bacterial load four days after focused ultrasound treatment when treating
      at high temperature (HT). The MPO amount remained unchanged between groups and
      days, indicating no change on local neutrophil recruitment in the abscess caused
      by the treatment. The white blood cell count remained unchanged between groups
      and days indicating that no systemic inflammatory response was caused by the
      treatment. CONCLUSIONS: Focused ultrasound induces a therapeutic effect in
      abscesses induced by MRSA. This effect is observed as a reduction of the number
      bacteria without significantly altering the amount of MPO at the site of a MRSA
      induced abscess. These initial results suggest that focused ultrasound is a
      viable option for the treatment of localized MRSA-related infections.

PMID- 24877839
TI  - Optimization of abdominal fat quantification on CT imaging through use of
      standardized anatomic space: a novel approach.
AB  - PURPOSE: The quantification of body fat plays an important role in the study of
      numerous diseases. It is common current practice to use the fat area at a single
      abdominal computed tomography (CT) slice as a marker of the body fat content in
      studying various disease processes. This paper sets out to answer three questions
      related to this issue which have not been addressed in the literature. At what
      single anatomic slice location do the areas of subcutaneous adipose tissue (SAT)
      and visceral adipose tissue (VAT) estimated from the slice correlate maximally
      with the corresponding fat volume measures? How does one ensure that the slices
      used for correlation calculation from different subjects are at the same anatomic
      location? Are there combinations of multiple slices (not necessarily contiguous)
      whose area sum correlates better with volume than does single slice area with
      volume? METHODS: The authors propose a novel strategy for mapping slice locations
      to a standardized anatomic space so that same anatomic slice locations are
      identified in different subjects. The authors then study the volume-to-area
      correlations and determine where they become maximal. To address the third issue,
      the authors carry out similar correlation studies by utilizing two and three
      slices for calculating area sum. RESULTS: Based on 50 abdominal CT data sets, the
      proposed mapping achieves significantly improved consistency of anatomic
      localization compared to current practice. Maximum correlations are achieved at
      different anatomic locations for SAT and VAT which are both different from the L4
      L5 junction commonly utilized currently for single slice area estimation as a
      marker. CONCLUSIONS: The maximum area-to-volume correlation achieved is quite
      high, suggesting that it may be reasonable to estimate body fat by measuring the
      area of fat from a single anatomic slice at the site of maximum correlation and
      use this as a marker. The site of maximum correlation is not at L4-L5 as commonly
      assumed, but is more superiorly located at T12-L1 for SAT and at L3-L4 for VAT.
      Furthermore, the optimal anatomic locations for SAT and VAT estimation are not
      the same, contrary to common assumption. The proposed standardized space mapping
      achieves high consistency of anatomic localization by accurately managing
      nonlinearities in the relationships among landmarks. Multiple slices achieve
      greater improvement in correlation for VAT than for SAT. The optimal locations in
      the case of multiple slices are not contiguous.

PMID- 24877840
TI  - Structure and adaptation of arteries to pulsatile flow: the case of the ascending
      aorta.
AB  - PURPOSE: The objectives are: (i) assess the development of the impedance of some
      arteries during the first decades of life; (ii) determine the influence of pulse
      rate in arterial impedance; (iii) compare the structure of some arterial segments
      with optimized structures with respect to blood flow; and (iv) explain the
      elongation of the ascending aorta throughout life in healthy subjects. METHODS: A
      model of the arterial network previously developed by the authors, together with
      data of lengths, diameters, and distensibilities of arterial segments reported in
      the literature were used. The impedances of the aorta and carotid artery were
      calculated based on that model. Similarly, the impedances of various arteries
      corresponding to heart rates of 65 bpm and 120 bpm were calculated. Values
      observed in arterial segments were compared with the respective optimal values
      from the viewpoint of hemodynamic performance. This allowed drawing conclusions
      on the arterial segments that might be critical with regard to hemodynamics.
      RESULTS: It was found that in healthy people impedances of the aorta and the
      carotid artery decrease markedly with age especially during body growth. It was
      also found that impedances of the main arteries do not significantly change with
      heart rate, even if sharp changes in arterial distensibility are observed. With
      respect to optimal flow performance, it was found that scaling between diameters
      of branching arteries is generally close to optimality, while the corresponding
      length scaling is far from optimality. It was also found that the ascending aorta
      and aortic arch are among those arterial segments whose lengths are much smaller
      than the optimum values. An explanation is offered for the age associated
      elongation of the aorta in healthy people. CONCLUSIONS: In healthy subjects, the
      human arterial system continues to optimize its performance at least until the
      age of 60.

PMID- 24877841
TI  - Occupational and patient exposure as well as image quality for full spine
      examinations with the EOS imaging system.
AB  - PURPOSE: EOS (EOS imaging S.A, Paris, France) is an x-ray imaging system that
      uses slot-scanning technology in order to optimize the trade-off between image
      quality and dose. The goal of this study was to characterize the EOS system in
      terms of occupational exposure, organ doses to patients as well as image quality
      for full spine examinations. METHODS: Occupational exposure was determined by
      measuring the ambient dose equivalents in the radiological room during a standard
      full spine examination. The patient dosimetry was performed using anthropomorphic
      phantoms representing an adolescent and a five-year-old child. The organ doses
      were measured with thermoluminescent detectors and then used to calculate
      effective doses. Patient exposure with EOS was then compared to dose levels
      reported for conventional radiological systems. Image quality was assessed in
      terms of spatial resolution and different noise contributions to evaluate the
      detector's performances of the system. The spatial-frequency signal transfer
      efficiency of the imaging system was quantified by the detective quantum
      efficiency (DQE). RESULTS: The use of a protective apron when the medical staff
      or parents have to stand near to the cubicle in the radiological room is
      recommended. The estimated effective dose to patients undergoing a full spine
      examination with the EOS system was 290 MUSv for an adult and 200 MUSv for a
      child. MTF and NPS are nonisotropic, with higher values in the scanning
      direction; they are in addition energy-dependent, but scanning speed independent.
      The system was shown to be quantum-limited, with a maximum DQE of 13%. The
      relevance of the DQE for slot-scanning system has been addressed. CONCLUSIONS: As
      a summary, the estimated effective dose was 290 MUSv for an adult; the image
      quality remains comparable to conventional systems.

PMID- 24877842
TI  - Assessment of individual organ doses in a realistic human phantom from neutron
      and gamma stimulated spectroscopy of the breast and liver.
AB  - PURPOSE: Understanding the radiation dose to a patient is essential when
      considering the use of an ionizing diagnostic imaging test for clinical diagnosis
      and screening. Using Monte Carlo simulations, the authors estimated the three
      dimensional organ-dose distribution from neutron and gamma irradiation of the
      male liver, female liver, and female breasts for neutron- and gamma-stimulated
      spectroscopic imaging. METHODS: Monte Carlo simulations were developed using the
      Geant4 GATE application and a voxelized XCAT human phantom. A male and a female
      whole body XCAT phantom was voxelized into 256 * 256 * 600 voxels (3.125 * 3.125
      * 3.125 mm(3)). A monoenergetic rectangular beam of 5.0 MeV neutrons or 7.0 MeV
      photons was made incident on a 2 cm thick slice of the phantom. The beam was
      rotated at eight different angles around the phantom ranging from 0 degrees  to
      180 degrees . Absorbed dose was calculated for each individual organ in the body
      and dose volume histograms were computed to analyze the absolute and relative
      doses in each organ. RESULTS: The neutron irradiations of the liver showed the
      highest organ dose absorption in the liver, with appreciably lower doses in other
      proximal organs. The dose distribution within the irradiated slice exhibited
      substantial attenuation with increasing depth along the beam path, attenuating to
      ~15% of the maximum value at the beam exit side. The gamma irradiation of the
      liver imparted the highest organ dose to the stomach wall. The dose distribution
      from the gammas showed a region of dose buildup at the beam entrance, followed by
      a relatively uniform dose distribution to all of the deep tissue structures,
      attenuating to ~75% of the maximum value at the beam exit side. For the breast
      scans, both the neutron and gamma irradiation registered maximum organ doses in
      the breasts, with all other organs receiving less than 1% of the breast dose.
      Effective doses ranged from 0.22 to 0.37 mSv for the neutron scans and 41 to 66
      mSv for the gamma scans. CONCLUSIONS: Neutron and gamma irradiation of a primary
      target organ was found to impart the majority of the total dose to the primary
      target organ (and other large organs) within the beam plane and considerably
      lower dose to proximal organs outside of the beam. These results also indicate
      that despite the use of a highly scattering particle such as a neutron, the dose
      from neutron stimulated emission computed tomography scans is on par with other
      clinical imaging techniques such as x-ray computed tomography (x-ray CT). Given
      the high nonuniformity in the dose across an organ during the neutron scan, care
      must be taken when computing average doses from neutron irradiations. The
      effective doses from neutron scanning were found to be comparable to x-ray CT.
      Further technique modifications are needed to reduce the effective dose levels
      from the gamma scans.

PMID- 24877843
TI  - Assessment of interpatient heterogeneity in tumor radiosensitivity for nonsmall
      cell lung cancer using tumor-volume variation data.
AB  - PURPOSE: In our previous work, the authors showed that a distribution of cell
      surviving fractions S2 in a heterogeneous group of patients could be derived from
      tumor-volume variation curves during radiotherapy for head and neck cancer. In
      this research study, the authors show that this algorithm can be applied to other
      tumors, specifically in nonsmall cell lung cancer. This new application includes
      larger patient volumes and includes comparison of data sets obtained at
      independent institutions. METHODS: Our analysis was based on two data sets of
      tumor-volume variation curves for heterogeneous groups of 17 patients treated for
      nonsmall cell lung cancer with conventional dose fractionation. The data sets
      were obtained previously at two independent institutions by using megavoltage
      computed tomography. Statistical distributions of cell surviving fractions S2 and
      clearance half-lives of lethally damaged cells T(1/2) have been reconstructed in
      each patient group by using a version of the two-level cell population model of
      tumor response and a simulated annealing algorithm. The reconstructed statistical
      distributions of the cell surviving fractions have been compared to the
      distributions measured using predictive assays in vitro. RESULTS: Nonsmall cell
      lung cancer presents certain difficulties for modeling surviving fractions using
      tumor-volume variation curves because of relatively large fractional hypoxic
      volume, low gradient of tumor-volume response, and possible uncertainties due to
      breathing motion. Despite these difficulties, cell surviving fractions S2 for
      nonsmall cell lung cancer derived from tumor-volume variation measured at
      different institutions have similar probability density functions (PDFs) with
      mean values of 0.30 and 0.43 and standard deviations of 0.13 and 0.18,
      respectively. The PDFs for cell surviving fractions S2 reconstructed from tumor
      volume variation agree with the PDF measured in vitro. CONCLUSIONS: The data
      obtained in this work, when taken together with the data obtained previously for
      head and neck cancer, suggests that the cell surviving fractions S2 can be
      reconstructed from the tumor volume variation curves measured during radiotherapy
      with conventional fractionation. The proposed method can be used for treatment
      evaluation and adaptation.

PMID- 24877844
TI  - A review of the use and potential of the GATE Monte Carlo simulation code for
      radiation therapy and dosimetry applications.
AB  - In this paper, the authors' review the applicability of the open-source GATE
      Monte Carlo simulation platform based on the GEANT4 toolkit for radiation therapy
      and dosimetry applications. The many applications of GATE for state-of-the-art
      radiotherapy simulations are described including external beam radiotherapy,
      brachytherapy, intraoperative radiotherapy, hadrontherapy, molecular
      radiotherapy, and in vivo dose monitoring. Investigations that have been
      performed using GEANT4 only are also mentioned to illustrate the potential of
      GATE. The very practical feature of GATE making it easy to model both a treatment
      and an imaging acquisition within the same framework is emphasized. The
      computational times associated with several applications are provided to
      illustrate the practical feasibility of the simulations using current computing
      facilities.

PMID- 24877845
TI  - Methods to correct dose-volume histograms based on LQ formalism.

PMID- 24877847
TI  - Alditols and monosaccharides from sorghum vinegar can attenuate platelet
      aggregation by inhibiting cyclooxygenase-1 and thromboxane-A2 synthase.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Vinegar has been used as both a common seasoning
      and a traditional Chinese medicine. Sorghum vinegar is an excellent source of
      physiological substances with multiple health benefits. AIM OF THIS STUDY: To
      evaluate the antiplatelet aggregation activity of alditols and monosaccharides
      extracted from sorghum vinegar and analysis its mechanism. MATERIALS AND METHODS:
      Alditol and monosaccharide extract (AME) from sorghum vinegar was first evaluated
      for antiplatelet activity using the turbidimetric method. Blood was collected
      from healthy volunteer donors. The platelet aggregation was induced by
      arachidonic acid (AA), collagen, adenosine diphosphate (ADP) and thrombin in
      vitro. AME was divided into three experimental groups with the concentration were
      0.10, 0.25 and 0.50 mg/mL. In order to determine the inhibitory activity of AME
      on COX1, TXS and TXA2 production experiments were conducted using the COX1, TXS
      and TXB2 EIA kit. Computational docking was used to find the docking pose of
      monosaccharides and alditols with COX1. RESULTS: AME showed significant induction
      of antiplatelet activity by arachidonic acid (AA), collagen, adenosine
      diphosphate (ADP) and thrombin in a concentration-dependent manner (p<0.05). AME
      (0.50 mg/mL) reduced the AA-induced aggregation rate to 10.35%+/-0.46%, which was
      comparable to acetylsalicylic acid (aspirin, ASA) (0.50 mg/mL, 6.35%+/-0.58%), a
      medical standard. Furthermore, AME strongly inhibited cyclooxygenase-1 (COX1) and
      thromboxane-A2 synthase (TXS), and subsequently attenuated thromboxane-A2 (TXA2)
      production. These findings indicated that AME attenuates platelet aggregation
      through the AA metabolism pathway. Computational docking showed that alditols (L
      erythritol, L-arabitol, xylitol and D-sorbitol), monosaccharides (D
      glucopyranose, D-fructofuranonse, D-xylopyranose, D-galactopyranose and D
      ribose), ethyl glucoside and 3,4-(methylenedioxy) mandelic acid could dock
      directly into the active site of COX1. CONCLUSION: Alditols and monosaccharides
      from sorghum vinegar inhibit multiple steps in the platelet aggregation pathway,
      and may be beneficial for the treatment of cardiovascular diseases.

PMID- 24877848
TI  - Neuroprotective effect of 1-methoxyoctadecan-1-ol from Uncaria sinensis on
      glutamate-induced hippocampal neuronal cell death.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: We isolated a single compound, 1-methoxyoctadecan
      1-ol (MOD), from dried hooks and stems of Uncaria sinensis, which is used in
      traditional Korean medicine to provide relief from various nervous related
      symptoms. MATERIALS AND METHODS: Neuroprotective effects of MOD against glutamate
      induced oxidative stress in HT22 cells were investigated by analyzing cell
      viability, lactate dehydrogenase, flow cytometry, reactive oxygen species (ROS)
      and Western blot assays. RESULTS: Exposure to glutamate alone resulted in
      remarkable hippocampal neuronal cell death; however, pretreatment with MOD
      resulted in suppression of neuronal death and ROS accumulation in connection with
      cellular Ca2+ level after exposure to glutamate. Stimulation by glutamate also
      caused significant protein level of phosphorylated p38 mitogen-activated protein
      kinases (MAPK), and dephosphorylated phosphatidylinositol-3 kinase (PI3K),
      however, pretreatment with MOD resulted in inhibition of these changes in protein
      level. Treatment with glutamate alone led to suppressed protein level of mature
      brain-derived neurotrophic factor (BDNF) and phosphorylated cAMP response element
      binding protein (CREB); however, pretreatment with MOD resulted in significant
      enhancement of this level of protein. Anti-oxidant N-acetyl-L-cysteine and both
      Ca2+ inhibitors, BAPTA and EGTA, showed effects similar to those of MOD in all
      proteins examined, except mature BDNF. CONCLUSIONS: Our results suggest that MOD
      mainly exerted neuroprotective effects in suppression of ROS accumulation and up
      regulation of mature BDNF in association with p38 MAPK and PI3K signaling in
      hippocampal neuronal cells.

PMID- 24877849
TI  - A review of the medicinal uses, phytochemistry and pharmacology of the genus
      Sapium.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Several species from the genus Sapium possess a
      broad range of medicinal properties and they have been used as traditional
      medicines by indigenous groups in several regions such as Malaysia, Africa,
      Southern China and Bolivia. Most of the species reported to possess therapeutic
      effects which are used for the treatment of skin-related diseases such as eczema
      and dermatitis, but they may also be used for overstrain, lumbago, constipation
      and hernia. Species of this genus are also used to treat wounds and snake bites.
      In addition, the saps/latex of Sapium glandulosum, Sapium indicum and Sapium
      sebiferum have/has toxic effects and are used as bird and fish poisons. This
      review discusses the current knowledge of the medicinal uses, phytochemistry,
      biological activities and toxicities of species from the genus Sapium to reveal
      their therapeutic potentials and gaps offering opportunities for future research.
      MATERIALS AND METHODS: This review is based on a literature study of scientific
      journals and books from libraries and electronic sources, such as ScienceDirect,
      PubMed and ACS. RESULTS: As many as 65 compounds are included in this review.
      They belong to different classes of compounds including flavonoids, terpenoids
      and several other types of compounds, such as alkaloids, phenolic acids and
      amides. The pharmacological studies revealed that various types of preparations,
      extracts and single compounds of species from this genus exhibited a broad
      spectrum of biological activities including antioxidant, antimicrobial, anti
      inflammatory and cytotoxic activities. However, Sapium glandulosum, Sapium
      indicum and Sapium sebiferum were reported to possess toxic effects and Sapium
      sebiferum was found to contain phorbol esters acting as a tumor-promoting agent.
      CONCLUSION: The genus Sapium consists of 23 accepted (high confidence) species.
      However, only very few of species have been phytochemically and pharmacologically
      studied. There is great potential to discover new chemical constituents from this
      genus because only a few species have been phytochemically investigated thus far.
      Only 27 compounds of 65 identified compounds have been studied for their
      biological activities. Several extracts and single compounds from this genus were
      reported to exhibit interesting biological activities such as antimicrobial,
      antioxidant and cytotoxic effects. Furthermore, the toxicity studies of some
      phorbol esters suggested that the compounds acted as potential tumor-promoting
      agents by stimulating protein kinase C. This is an interesting fact in which a
      plant with medicinal properties also possesses toxic effects as well. Therefore,
      more clinical studies on the toxicity of the extracts of the plants and the
      compounds isolated from this genus are also crucial to ensure their safety and to
      assess their eligibility for use as sources for modern medicines.

PMID- 24877851
TI  - Comparative systematic review and meta-analysis of compression modalities for the
      promotion of venous ulcer healing and reducing ulcer recurrence.
AB  - OBJECTIVE: This was a systematic review of the literature to determine which
      compression method is superior in promoting ulcer healing and reducing recurrence
      in patients with lower extremity venous ulcer disease. METHODS: We conducted a
      comprehensive search of multiple databases for randomized and nonrandomized
      comparative studies from 1990 to December 2013. RESULTS: We identified 36 studies
      and two Cochrane systematic reviews. Many studies had moderate risk of bias. We
      found no overall difference between compression stockings vs compression bandages
      with respect to ulcer healing, time to ulcer healing, or ulcer recurrence
      outcomes. When we compared stockings vs short stretch bandages, stockings were
      superior with respect to ulcer healing. However, stockings compared with four
      layer systems showed no difference in ulcer healing outcomes. When four-layer
      systems were compared with compression with less than four layers, there was also
      no significant difference in ulcer healing outcomes. Similarly, short stretch
      bandages were not superior to long stretch bandages with respect to ulcer
      healing, time to ulcer healing, or ulcer recurrence. One Cochrane review
      presented many additional comparisons and reported increased wound healing with
      compression compared with no compression, with multicomponent systems over single
      component systems, and compression systems with an elastic component over no
      elastic component. Another Cochrane review demonstrated a reduction in recurrence
      with compression in patients with healed ulcers. CONCLUSIONS: At least moderate
      quality evidence supports compression over no compression, multicomponent systems
      over single component systems, and systems with an elastic component over those
      without. We did not find significant differences with respect to ulcer healing
      outcomes for other comparisons. Low-quality evidence supports the effect of
      compression on ulcer recurrence.

PMID- 24877852
TI  - Clinical outcome of an extended proximal seal zone with the AFX endovascular
      aortic aneurysm system.
AB  - OBJECTIVE: Despite improvements in endograft technology, operator skill, and
      patient selection, endovascular aneurysm repair continues to be associated with
      device-related complications. A retrospective, observational study was undertaken
      to evaluate the clinical outcome and imaging findings of a unique device having
      externally-mounted, conformable graft material. METHODS: Infrarenal abdominal
      aortic aneurysms were treated with the Endologix, Inc AFX endovascular aortic
      aneurysm system (Irvine, Calif) endograft in 108 consecutive patients over a 25
      month period at two U.S. clinical sites. Baseline characteristics and procedural
      outcomes were reviewed by independent monitors. Serial computed tomography (CT)
      imaging assessments were performed by an independent core laboratory. Aortic neck
      characteristics and graft apposition were analyzed from center line-reformatted
      CT data sets in 37 patients in an imaging cohort comprising subjects with high
      resolution baseline and follow-up CT imaging for precise assessment of aortic
      neck characteristics. The mean follow-up was 11 +/- 5 months overall, 9 +/- 6
      months in patients with core laboratory imaging, and 5 +/- 2 months for patients
      in the imaging cohort. RESULTS: Among the 108 patients, 103 (95%) had intact
      aneurysms and five (4.6%) were treated for rupture; 80 (74%) were male and 28
      (26%) were female. On average, 2.3 +/- 0.7 endograft components were implanted
      per patient and no adjunctive proximal neck bare stents were used. There were no
      perioperative deaths in patients with intact aneurysms; two patients who
      presented with ruptured aortic aneurysms (40%) died. Major adverse events
      occurred within 30 days of implantation in two patients (1.9%) with intact
      aneurysms. Type II endoleaks were evident on completion angiography in 18
      patients (16.7%). Core laboratory analysis of CT studies identified two patients
      with type Ia endoleaks (2.3%), two with type III endoleaks (2.3%), and five with
      type II endoleaks (5.7%). Aneurysm-related secondary procedures were required in
      five patients over the first year of follow-up (4.6%). No patient developed
      endograft limb occlusion or aneurysm rupture and there were no open surgical
      conversions. In the imaging cohort, 360 degrees  graft-to-aortic wall apposition
      was continuous over a length of 25 +/- 17 mm and extended the seal zone an
      average of 5 mm beyond the end of the anatomic neck. Early sac regression was
      correlated with neck length (P = .019) and graft-to-aortic apposition surface
      area (P = .039). CONCLUSIONS: The real-world use of the AFX endograft was
      associated with a low rate of device-and procedure-related complications. The
      ability to achieve an extended seal zone beyond the anatomical neck might in part
      contribute to positive outcomes, including the low type Ia and type II endoleak
      rate. These findings suggest that the AFX device might offer some advantages over
      other currently marketed endografts, but confirmation awaits the availability of
      longer-term outcome data.

PMID- 24877853
TI  - Concomitant asymptomatic internal carotid artery and persistent primitive
      hypoglossal artery stenosis treated by endovascular stenting with proximal
      embolic protection.
AB  - The persistent primitive hypoglossal artery (PPHA) is a rare fetal variant of
      carotid-basilar anastomosis that increases the risk of ischemia and embolic
      infarction within the posterior cerebral circulation in patients with carotid
      stenosis proximal to the origin of the PPHA. A man presented with severe stenosis
      of the right internal carotid artery with extension to the origin of a PPHA. The
      area of stenosis was at a high position, which contraindicated carotid
      endarterectomy. Therefore, stenting was performed with proximal reversal of flow
      embolic protection. The unique anatomic and technical challenges associated with
      this case are reviewed in detail. 

PMID- 24877854
TI  - Patients carrying CYP2C19 loss of function alleles have a reduced response to
      clopidogrel therapy and a greater risk of in-stent restenosis after endovascular
      treatment of lower extremity peripheral arterial disease.
AB  - OBJECTIVE: This study evaluated the relationship between the cytochrome P450
      (CYP) 2C19 genotype and the antiplatelet effect of clopidogrel therapy and
      investigated whether genotyping can predict the risk of ischemic events after
      endovascular treatment (ET) of lower extremity peripheral arterial disease.
      METHODS: From January 2011 to July 2012, 120 consecutive patients with
      arteriosclerosis obliterans (TransAtlantic Inter-Society Consensus for the
      Management of Peripheral Arterial Disease [TASC II] A-C) in the superficial
      femoral artery were included in a prospectively maintained database. Patients
      received 75 mg clopidogrel and 100 mg aspirin daily for at least 5 days before
      TaqMan (Life Technologies, Grand Island, NY) of CYP2C19 single-nucleotide
      polymorphisms and thromboelastography of the clopidogrel response. ET was
      subsequently performed, and follow-up evaluations, including duplex ultrasound
      imaging and ankle-brachial index assessment, were performed at 1, 3, 6, and 12
      months after ET. During the follow-up, stent patency was assessed by ultrasound
      imaging, computed tomography angiography, or digital subtraction angiography.
      RESULTS: A total of 74 ET procedures were performed. Fifty of the enrolled
      patients (41.7%) completed the follow-up examinations and were included in the
      analysis. The mean duration of follow-up was 9.8 +/- 2.1 months (range, 1-30
      months). Carriers of at least one CYP2C19 loss-of-function (LOF) allele had a
      diminished pharmacodynamic response to clopidogrel (51.6 +/- 20.1 vs. 39.8 +/-
      15.2 for patients without and with LOF alleles, respectively; P = .022). Carriers
      of one LOF allele had an increased incidence of ischemic events compared with
      patients without any LOF alleles (59.0% vs. 20.8%, respectively; P = .008). This
      trend was even more evident in patients with two LOF alleles compared with
      patients with no LOF alleles (100% vs. 20.8% ischemic events; P = .002). The
      cumulative primary patency rate at 12 months was 56.0%, with significant
      differences between groups (73.1% vs. 34.6% in patients without and with LOF
      alleles, respectively; P = .0.006). CYP2C19 LOF carrier status was associated
      with an increased rate of primary end points (P = .007). On the basis of their
      adenosine diphosphate-induced platelet aggregation, patients with high platelet
      reactivity had a significantly higher risk of ischemic events (P = .012). CYP2C19
      genotypic classification (adjusted hazard ratio, 2.688; 95% confidence interval,
      1.366-5.288; P = .004) and history of smoking (adjusted hazard ratio, 2.430; 95%
      confidence interval, 1.024-5.765; P = .044) were independent risk factors for
      ischemic events. CONCLUSIONS: CYP2C19 LOF alleles were associated with a
      diminished platelet response to clopidogrel treatment. Patients carrying CYP2C19
      LOF alleles who are treated with clopidogrel may trend toward a poor prognosis
      after ET.

PMID- 24877855
TI  - Predicted shortfall in open aneurysm experience for vascular surgery trainees.
AB  - OBJECTIVE: Since the introduction of endovascular aneurysm repair (EVAR), the
      volume of open aneurysm repair (OAR) has steadily declined since 2000. The
      introduction of next-generation devices and branched and fenestrated endograft
      technology continues to increase the anatomic applicability of EVAR, further
      decreasing the need for OAR. This study models the decline in OAR and uses
      historical trends to forecast future decline in volume and its potential effect
      on vascular surgery training. METHODS: An S-curve modified logistic function was
      used to model the effect of introducing a new technology (EVAR) on the standard
      management of abdominal aortic aneurysm (AAA) with OAR starting in the year 2000,
      when an International Classification of Diseases, Ninth Revision, code was first
      introduced for EVAR. Patients who underwent EVAR and OAR for AAA were determined
      using the Nationwide Inpatient Sample from 1998 to 2011. Weighted samples and
      data from the United States Census Bureau were used to extrapolate these numbers
      to estimate population statistics. The number of cases completed at teaching
      hospitals was calculated using the Nationwide Inpatient Sample, and Accreditation
      Council for Graduate Medical Education case logs were used to forecast the number
      of cases completed by vascular surgery trainees. RESULTS: The highest number of
      OAR cases in this study was 42,872 in 2000 compared with just 10,039 in 2011.
      This was mirrored by a rise in EVAR from 2358 cases in 2000 (5.2%) to 35,028 in
      2011 (76.5% by volume). Of the OAR volume in 2011, 6055 cases (60.3%) were
      completed at teaching institutions. An S-curve model with a correlation
      coefficient of R2 = 0.982 predicted 3809 open AAA cases at teaching hospitals by
      2015, 2162 by 2020, and 1231 by 2025. When compared with the 2011 Accreditation
      Council for Graduate Medical Education National Resident Report, vascular surgery
      residents had 44.4% utilization with regard to OAR (2690 cases covered of 6055
      total). When combined with the increase in vascular surgery trainees and lower
      number of open repairs, vascular fellows will complete about 10 OAR cases in 2015
      and five OAR cases in 2020. CONCLUSIONS: The decreasing number of OAR cases will
      limit exposure for vascular trainees, who may be ill equipped to treat patients
      who require open repair beyond 2015. Additional methods for providing OAR
      training should be explored.

PMID- 24877856
TI  - Polyclonal intravenous immunoglobulin: an important additional strategy in
      sepsis?
AB  - Sepsis syndrome is characterized by a systemic inflammatory response to infection
      potentially leading to acute organ failure and rapid decline to death. Polyclonal
      intravenous immune globulin, a blood product derived from human donor blood, in
      addition to antiinfective activities, also exerts a broad antiinflammatory and
      immunomodulating effect. Intravenous immunoglobulin (IVIg) has been proposed as
      adjuvant therapy for sepsis even though the clinical studies demonstrating their
      efficacy and safety are relatively small. Several systematic reviews and meta
      analyses of intravenous immunoglobulin treatment in sepsis have been performed.
      As a result of heterogeneity across studies and inconsistencies in results, the
      majority have concluded that more evidence, coming from large, well-conducted
      randomized controlled trials (RCTs), is required. Moreover the appropriate timing
      of administration and the identification of specific clinical settings represent
      a key factor to maximizing their beneficial effect. The authors, in this
      revision, review the basic mechanisms of action of IVIg, the rationale for their
      use, and their clinical applications. 

PMID- 24877857
TI  - Changes in health related quality of life in women and men undergoing radiation
      treatment for head and neck cancer and the impact of smoking status in the
      radiation treatment period.
AB  - PURPOSE: The aim of this study was to evaluate health-related quality of life
      (HRQOL) in women and men undergoing radiation treatment for head and neck cancer
      through the intervention period and examine if age, body mass index (BMI) and
      smoking status at baseline may modify changes in HRQOL. METHODS: HRQOL was
      examined by the European Organization for Research and Treatment of Cancer
      (EORTC) QLQ-C30 and the EORTC QLQ-H&N35, in the beginning and end of the
      treatment period in 65 patients at the University Hospital in Northern Norway.
      Changes in HRQOL were calculated and compared by paired sample T-tests. Linear
      multiple regression analyses were used to examine if baseline characteristics had
      any influence towards HRQOL changes. RESULTS: Most aspects of HRQOL declined
      substantially and significantly (p < 0.001) with a magnitude of more than one
      standard deviation during the radiation treatment period irrespective of sex and
      age. Smoking status at baseline had some, albeit minor, influence on changes in
      HRQOL. Patients who continued smoking during therapy had significantly higher
      decline in several aspects of HRQOL, compared to patients who stopped smoking.
      CONCLUSIONS: HRQOL declined with substantial magnitude in patients undergoing
      radiation treatment for head and neck cancer, but smoking cessation may modify
      the declining quality of life.

PMID- 24877858
TI  - Hermeneutic phenomenological interpretations of patients with head and neck
      neoplasm experiences living with radiation-induced xerostomia: the price to pay?
AB  - PURPOSE: Patients with head and neck neoplasms often experience a number of
      persistent treatment related symptoms including xerostomia. The impact of
      xerostomia can be profound and wearing on the patients, hence negatively
      influencing their quality of life. The purpose of this study was to explore the
      in-depth experiences of the patients living with radiation-induced xerostomia.
      METHODS AND SAMPLE: This was a hermeneutic phenomenological study inspired by the
      Philosophy of Paul Ricoeur. Research data were retrieved with individual
      narratives from 15 patients diagnosed with head and neck neoplasm that underwent
      radiotherapy. Interpretation proceeded through three phases: naive reading,
      structural analysis and comprehensive understanding. RESULTS: Five themes
      consisting of ten sub-themes emerged from the narratives reflecting on the
      patients' lived experiences. The themes were "suffering of the body", "suffering
      of the person's world", "being helpless against xerostomia", "suffering of the
      mind" and "being alone". The comprehensive understanding disclosed new
      possibilities for being-in-the world in relation to living with xerostomia.
      CONCLUSION: The precedent consideration of xerostomia mainly as a physical side
      effect of radiotherapy was outweighed by the social and psychological effects
      revealed by this study. These xerostomia's effects are inflicted on the patients
      with an obvious reflection on their perceived quality of life. The findings call
      upon a shift towards acknowledging the severity of xerostomia and the need to
      care for these patients holistically.

PMID- 24877860
TI  - The origins of irritable bowel syndrome: experience of a lifetime.

PMID- 24877859
TI  - Retrospective study of radiotherapy-induced skin reactions in breast cancer
      patients: reduced incidence of moist desquamation with a hydroactive colloid gel
      versus dexpanthenol.
AB  - PURPOSE: Dermatitis is a very frequent and distressing side effect of radiation
      therapy that may necessitate a treatment interruption when evolving towards more
      severe forms such as moist desquamation (MD). The aim of this study was to
      compare the efficacy of two topical agents, a dexpanthenol cream vs a hydroactive
      colloid gel combining absorbing and moisturising properties, in preventing MD in
      breast cancer patients. METHODS: This retrospective study compared two successive
      groups of breast cancer patients undergoing radiotherapy after breast-sparing
      surgery between 2008 and 2012. A group of 267 patients applied a 5% dexpanthenol
      cream on the irradiated zone throughout the course of their radiotherapy. Another
      group of 216 patients applied first the dexpanthenol cream then replaced it by
      the hydroactive colloid gel after 11-14 days of radiotherapy. Radiation treatment
      (total dose, technique, and equipment) was the same for the two groups. The
      clinical outcomes were the occurrence and time to onset of moist desquamation.
      KEY RESULTS: The overall incidence of MD was significantly lower in patients who
      applied the hydroactive colloid gel (16%) than in those who applied the
      dexpanthenol cream (32%, odds-ratio = 0.35). Also, MD occurred significantly
      later with the hydroactive colloid gel than with the dexpanthenol cream (hazard
      ratio = 0.39). CONCLUSIONS: Compared with the dexpanthenol cream, the hydroactive
      colloid gel significantly reduced the risk of developing MD in patients
      undergoing radiotherapy for breast cancer. These promising results warrant
      further research on the efficacy of hydroactive colloid gels in managing
      radiation dermatitis.

PMID- 24877862
TI  - A gut feeling you should never ignore.

PMID- 24877861
TI  - A rare cause of a focal liver lesion.

PMID- 24877863
TI  - An unusual cause of gastrointestinal bleeding and encephalopathy in an elderly
      woman.

PMID- 24877864
TI  - Studies in human intestinal tissues: is it time to reemphasize research in human
      immunology?

PMID- 24877865
TI  - The good, the not so bad, and the ugly.

PMID- 24877866
TI  - Averting hepatocellular carcinoma in chronic hepatitis B with antiviral therapy:
      tipping the balance or not yet?

PMID- 24877867
TI  - Eltrombopag for thrombocytopenic patients with hepatitis C virus infection and
      cirrhosis.

PMID- 24877868
TI  - Acute hepatitis in pregnancy.

PMID- 24877869
TI  - Is treatment of moderate thrombocytopenia indicated for patients with HCV
      infection and cirrhosis?

PMID- 24877870
TI  - Reply: To PMID 24126097.

PMID- 24877871
TI  - Eltrombopag for thrombocytopenic patients with chronic HCV infection.

PMID- 24877872
TI  - An unusual cause of odynophagia in a patient with eosinophilic esophagitis.

PMID- 24877873
TI  - From the discovery of monoclonal antibodies to their therapeutic application: an
      historical reappraisal.
AB  - Vertebrate make billions of different antibodies, each with a binding site that
      recognizes a specific region of a macromolecule. The hybridoma technique allows
      monoclonal antibodies, highly specific antibodies produced in the laboratory by a
      variety of methods. In the last 35 years since the first process for creating
      monoclonal antibodies was introduced, their application have improved the growing
      biotechnology industry, but the most important application concerns the therapy
      of human malignancies. 

PMID- 24877875
TI  - Crammed signaling motifs in the T-cell receptor.
AB  - Although the T cell antigen receptor (TCR) is long known to contain multiple
      signaling subunits (CD3gamma, CD3delta, CD3E and CD3zeta), their role in signal
      transduction is still not well understood. The presence of at least one
      immunoreceptor tyrosine-based activation motif (ITAM) in each CD3 subunit has led
      to the idea that the multiplication of such elements essentially serves to
      amplify signals. However, the evolutionary conservation of non-ITAM sequences
      suggests that each CD3 subunit is likely to have specific non-redundant roles at
      some stage of development or in mature T cell function. The CD3E subunit is
      paradigmatic because in a relatively short cytoplasmic sequence (~55 amino acids)
      it contains several docking sites for proteins involved in intracellular
      trafficking and signaling, proteins whose relevance in T cell activation is
      slowly starting to be revealed. In this review we will summarize our current
      knowledge on the signaling effectors that bind directly to the TCR and we will
      propose a hierarchy in their response to TCR triggering. 

PMID- 24877876
TI  - Diarrhoea due to allergy to egg: is there a role for specific IgG?

PMID- 24877877
TI  - Gold nanoprisms for photothermal cell ablation in vivo.
AB  - AIM: To develop new methodologies for selective cell ablation in a temporally and
      spatially precise fashion in model organisms. MATERIALS & METHODS: living polyps
      (Hydra vulgaris) treated with gold nanoprisms were near-infrared (NIR) irradiated
      and the photothermal effects evaluated at whole-animal, cellular and molecular
      levels. RESULTS: Nanoprisms showed good efficiency of internalization in living
      specimens, with no sign of toxicity; under NIR irradiation they induced cell
      death and the overexpression of the hsp70 gene. CONCLUSION: gold nanoprisms could
      be employed as efficient heat mediators in model organisms, and NIR-triggered
      cell ablation may represent a new advanced tool to study cell function. Solving
      bioethical and economical issues, invertebrates may provide alternative models
      bridging the gap between cell research and preclinical studies of photothermal
      therapy.

PMID- 24877874
TI  - Cooperativity among secretory IgA, the polymeric immunoglobulin receptor, and the
      gut microbiota promotes host-microbial mutualism.
AB  - Secretory IgA (SIgA) antibodies in the intestinal tract form the first line of
      antigen-specific immune defense, preventing access of pathogens as well as
      commensal microbes to the body proper. SIgA is transported into external
      secretions by the polymeric immunoglobulin receptor (pIgR). Evidence is reported
      here that the gut microbiota regulates production of SIgA and pIgR, which act
      together to regulate the composition and activity of the microbiota. SIgA in the
      intestinal mucus layer helps to maintain spatial segregation between the
      microbiota and the epithelial surface without compromising the metabolic activity
      of the microbes. Products shed by members of the microbial community promote
      production of SIgA and pIgR by activating pattern recognition receptors on host
      epithelial and immune cells. Maternal SIgA in breast milk provides protection to
      newborn mammals until the developing intestinal immune system begins to produce
      its own SIgA. Disruption of the SIgA-pIgR-microbial triad can increase the risk
      of infectious, allergic and inflammatory diseases of the intestine. 

PMID- 24877879
TI  - Evaluation of suitable target antigens and immunoassays for high-accuracy immune
      monitoring of cytomegalovirus and Epstein-Barr virus-specific T cells as targets
      of interest in immunotherapeutic approaches.
AB  - Adoptive immunotherapy with donor-derived antiviral T cells can prevent viral
      complications such as with cytomegalovirus (CMV) and Epstein-Barr virus (EBV). In
      this context accurate monitoring of cellular immunity is essential and requires
      suitable quantitative and qualitative assays for high-throughput screening. We
      comparatively analyzed 57 HLA-typed healthy donors for memory T-cell responses to
      CMV- and EBV-derived proteins, peptide pools and single HLA-restricted peptides
      by five commonly used immunoassays in parallel: enzyme-linked immunospot
      (ELISPOT), cytokine secretion assay (CSA), intracellular cytokine staining (ICS),
      enzyme-linked immunosorbent assay (ELISA) and pMHC multimer staining. T-cell
      responses varied greatly between the different target antigens in the
      investigated assays. IFN-gamma ELISPOT consistently detected the highest T-cell
      response levels against CMV and EBV. CMV-specific T cells were detected in 100%
      of CMV-seropositive donors tested using CMVpp65 protein and/or overlapping
      CMVpp65 peptide pool. CMV-specific T cells in HLA-A*02:01-positive/CMV
      seropositive donors were identified directly by HLA-A02/CMVpp65 (A02pp65)
      multimer staining and, after short in vitro stimulation with HLA-A*02:01
      restricted pp65 peptide, by ELISPOT, ELISA, ICS and CSA. A peptide-specific T
      cell response was detected in only 4 HLA-A*02:01-positive donors (50%). Despite
      A02pp65 peptide negativity, T-cell responses to CMVpp65 protein and/or
      overlapping peptide pool were detected. Comparing the specific immune response
      against EBV antigens in healthy donors overall, BZLF1-specific T cells (<92.9%
      peptides, <56.3% peptide pool) were more frequent than EBNA-specific T cells
      (<64.3% peptides, <46.9% peptide pool) with higher percentage of positive
      findings for single HLA-restricted EBV peptides. T-cell response against HLA-B*08
      peptide epitopes was predominant (multimer staining: EBNA3A: 9/14 and BZLF1:
      7/14, IFN-gamma ELISPOT: EBNA3A: 13/14 and BZLF1: 11/14). The fact that responses
      to EBV-specific antigens were not detected in every single EBV-seropositive donor
      as well as that the T-cell frequencies in response to the investigated EBV
      antigens differed strongly in the donor cohort indicates that these epitopes are
      less immunodominant than CMVpp65. Taken together, precise monitoring of T-cell
      immunity against infectious agents in potential T-cell donors and post-transplant
      recipients requires individual selection of antigens and immunoassays for the
      efficient detection and generation of clinically relevant T cells. Due to its
      lower detection limit and direct visualization of each IFN-gamma-secreting cell
      we identified ELISPOT analysis to be preferable for high-throughput pre
      screening. CSA was found to be advantageous for a more detailed analysis of
      antigen-specific T-cell subsets.

PMID- 24877880
TI  - Fracture analysis for biological materials with an expanded cohesive zone model.
AB  - In this study, a theoretical framework for simulation of fracture of bone and
      bone-like materials is provided. An expanded cohesive zone model with
      thermodynamically consistent framework has been proposed and used to investigate
      the crack growth resistance of bone and bone-like materials. The reversible
      elastic deformation, irreversible plastic deformation caused by large deformation
      of soft protein matrix, and damage evidenced by the material separation and crack
      nucleation in the cohesive zone, were all taken into account in the model.
      Furthermore, the key mechanisms in deformation of biocomposites consisting of
      mineral platelets and protein interfacial layers were incorporated in the
      fracture process zone in this model, thereby overcoming the limitations of
      previous cohesive zone modeling of bone fracture. Finally, applications to
      fracture of cortical bone and human dentin were presented, which showed good
      agreement between numerical simulation and reported experiments and substantiated
      the effectiveness of the model in investigating the fracture behavior of bone
      like materials. 

PMID- 24877881
TI  - Effects of fabrication on the mechanics, microstructure and micromechanical
      environment of small intestinal submucosa scaffolds for vascular tissue
      engineering.
AB  - In small intestinal submucosa scaffolds for functional tissue engineering, the
      impact of scaffold fabrication parameters on success rate may be related to the
      mechanotransductory properties of the final microstructural organization of
      collagen fibers. We hypothesized that two fabrication parameters, 1) preservation
      (P) or removal (R) of a dense collagen layer present in SIS and 2) SIS in a final
      dehydrated (D) or hydrated (H) state, have an effect on scaffold void area,
      microstructural anisotropy (fiber alignment) and mechanical anisotropy (global
      mechanical compliance). We further integrated our experimental measurements in a
      constitutive model to explore final effects on the micromechanical environment
      inside the scaffold volume. Our results indicated that PH scaffolds might exhibit
      recurrent and large force fluctuations between layers (up to 195 pN), while
      fluctuations in RH scaffolds might be larger (up to 256 pN) but not as recurrent.
      In contrast, both PD and RD groups were estimated to produce scarcer and smaller
      fluctuations (not larger than 50 pN). We concluded that the hydration parameter
      strongly affects the micromechanics of SIS and that an adequate choice of
      fabrication parameters, assisted by the herein developed method, might leverage
      the use of SIS for functional tissue engineering applications, where forces at
      the cellular level are of concern in the guidance of new tissue formation.

PMID- 24877882
TI  - Prevention of measles spread on a paediatric ward.
AB  - Since measles is a highly contagious respiratory infection with significant
      airborne transmission risk in hospitals, effective prevention measures are
      crucial. After a mother accompanying her child on a paediatric ward lacking a
      negative pressure room was diagnosed with measles, exposed persons without
      evidence of immunity (documentary evidence of receiving two doses of measles
      mumps-rubella vaccine) were treated with vaccination or intravenous
      immunoglobulin (IVIG). The interruption of transmission with these treatments was
      evaluated. There were 44 children and 101 adults exposed to the index patient.
      Twenty-five children and 88 adults were considered immune, providing evidence of
      immunity. Nineteen children and 13 adults were either given vaccination or IVIG
      for post-exposure prophylaxis (PEP). There were no additional cases of measles
      after 3 weeks follow-up. We conclude that measles is highly preventable by
      adequate PEP with vaccination or IVIG in a healthcare setting that lacks the
      benefit of a negative pressure room.

PMID- 24877878
TI  - Sirtuins: guardians of mammalian healthspan.
AB  - The first link between sirtuins and longevity was made 15 years ago in yeast.
      These initial studies sparked efforts by many laboratories working in diverse
      model organisms to elucidate the relations between sirtuins, lifespan, and age
      associated dysfunction. Here, we discuss the current understanding of how
      sirtuins relate to aging. We focus primarily on mammalian sirtuins SIRT1, SIRT3,
      and SIRT6, the three sirtuins for which the most relevant data are available.
      Strikingly, a large body of evidence now indicates that these and other mammalian
      sirtuins suppress a variety of age-related pathologies and promote healthspan.
      Moreover, increased expression of SIRT1 or SIRT6 extends mouse lifespan. Overall,
      these data point to important roles for sirtuins in promoting mammalian health,
      and perhaps in modulating the aging process. 

PMID- 24877884
TI  - Tachyarrhythmia-induced cerebral sinovenous thrombosis in a neonate without
      cardiac malformation.

PMID- 24877883
TI  - Best of both worlds: on the complementarity of ligand-based and structure-based
      virtual screening.
AB  - Virtual screening with docking is an integral component of drug design,
      particularly during hit finding phases. While successful prospective studies of
      virtual screening exist, it remains a significant challenge to identify best
      practices a priori due to the many factors that influence the final outcome,
      including targets, data sets, software, metrics, and expert knowledge of the
      users. This study investigates the extent to which ligand-based methods can be
      applied to improve structure-based methods. The use of ligand-based methods to
      modulate the number of hits identified using the protein-ligand complex and also
      the diversity of these hits from the crystallographic ligand is discussed. In
      this study, 40 CDK2 ligand complexes were used together with two external data
      sets containing both actives and inactives from GlaxoSmithKline (GSK) and actives
      and decoys from the Directory of Useful Decoys (DUD). Results show how ligand
      based modeling can be used to select a more appropriate protein conformation for
      docking, as well as to assess the reliability of the docking experiment. The time
      gained by reducing the pool of virtual screening candidates via ligand-based
      similarity can be invested in more accurate docking procedures, as well as in
      downstream labor-intensive approaches (e.g., visual inspection) maximizing the
      use of the chemical and biological information available. This provides a
      framework for molecular modeling scientists that are involved in initiating
      virtual screening campaigns with practical advice to make best use of the
      information available to them. 

PMID- 24877885
TI  - The up-regulation of endothelin-1 and down-regulation of miRNA-125a-5p, -155, and
      -199a/b-3p in human atherosclerotic coronary artery.
AB  - BACKGROUND: Previous studies have reported important roles of endothelin-1 (ET-1)
      and angiotensin II (Ang II) in the pathogenesis of atherosclerosis. However, the
      expression of these two proteins and the underlying mechanisms in human
      atherosclerotic coronary arteries are largely unknown. METHODS: We examined the
      expression of ET-1 and Ang II in pericardial fluid and coronary arteries from 25
      individuals (n = 25) using enzyme-linked immuno sorbent assay (ELISA) and
      immunohistochemistry. Twelve patients died from acute coronary syndrome were
      classified as atherosclerotic plaque group (AP group) (n = 12), while 13 patients
      died from other causes were classified as non-AP group (n = 13). Meanwhile, we
      performed reverse transcription-polymerase chain reaction (RT-PCR) to measure the
      expression of six microRNAs targeting ET-1 in formalin-fixed, paraffin-embedded
      coronary arteries. RESULTS: Our data showed that ET-1 was significantly higher in
      both pericardial fluid and coronary arteries from AP group. However, Ang II
      showed no significant difference in pericardial fluid between the two groups,
      while it was even significantly lower in coronary arteries from AP group.
      Besides, miR-125a-5p, miR-155, and miR-199a/b-3p, which suppressed the expression
      of ET-1, were down-regulated in the coronary arteries from AP group. CONCLUSION:
      The up-regulation of ET-1, regulated by miR-125a-5p, miR-155, and miR-199a/b-3p,
      indicated that ET-1 played an important role in human coronary atherosclerosis.
      SUMMARY: We focused on the human coronary arteries with atherosclerotic plaques.
      The expression of ET-1, as well as its upstream miRNAs, was determined. Unlike
      any of previous study regarding miRNAs expression, we could exclude the
      discrepancy of artery-bed-specific miRNA expression. Besides, our data indicated,
      to some degree, that ET-1 might play a more vital role than Ang II in coronary
      atherosclerosis.

PMID- 24877886
TI  - 3D photography is as accurate as digital planimetry tracing in determining burn
      wound area.
AB  - BACKGROUND: In the paediatric population careful attention needs to be made
      concerning techniques utilised for wound assessment to minimise discomfort and
      stress to the child. AIM: To investigate whether 3D photography is a valid
      measure of burn wound area in children compared to the current clinical gold
      standard method of digital planimetry using VisitrakTM. METHOD: Twenty-five
      children presenting to the Stuart Pegg Paediatric Burn Centre for burn dressing
      change following acute burn injury were included in the study. Burn wound area
      measurement was undertaken using both digital planimetry (VisitrakTM system) and
      3D camera analysis. Inter-rater reliability of the 3D camera software was
      determined by three investigators independently assessing the burn wound area.
      RESULTS: A comparison of wound area was assessed using intraclass correlation co
      efficients (ICC) which demonstrated excellent agreement 0.994 (CI 0.986, 0.997).
      Inter-rater reliability measured using ICC 0.989 (95% CI 0.979, 0.995)
      demonstrated excellent inter-rater reliability. Time taken to map the wound was
      significantly quicker using the camera at bedside compared to VisitrakTM 14.68
      (7.00)s versus 36.84 (23.51)s (p<0.001). In contrast, analysing wound area was
      significantly quicker using the VisitrakTM tablet compared to Dermapix((r))
      software for the 3D Images 31.36 (19.67)s versus 179.48 (56.86)s (p<0.001).
      CONCLUSION: This study demonstrates that images taken with the 3D LifeVizTM
      camera and assessed with Dermapix((r)) software is a reliable method for wound
      area assessment in the acute paediatric burn setting.

PMID- 24877892
TI  - Laughing and crying: mixed emotions, compassion, and the effectiveness of a
      YouTube PSA about skin cancer.
AB  - Emotionally evocative public service announcements are one way that public health
      advocates hope to persuade people to take action against skin cancer, the most
      common type of cancer in the United States. This article describes an experiment
      (N = 193) to test the ways mixed emotional appeals influence communication and
      health outcomes. The data indicate that mixed emotional appeals foster feelings
      of compassion, which in turn motivate individual and social behaviors. The
      findings also provide insight into how audience reactions of fear impact
      postmessage behaviors. Implications for future research and health message design
      are discussed. 

PMID- 24877893
TI  - Influence of surface concentration on poly(vinyl alcohol) behavior at the water
      vacuum interface: a molecular dynamics simulation study.
AB  - Poly(vinyl alcohol) (PVA) is an amphiphilic macromolecule with surfactant
      activity. The peculiar behavior of this polymer at the water-air interface is at
      the basis of its use as material for hydrated microdevices, films, and
      nanofibers. This work aims to investigate the behavior of PVA and water within
      the surface domain of highly diluted aqueous solutions by means of atomistic
      molecular dynamics simulations. Monodisperse atactic oligomers of 30 residues
      were distributed within water slabs in a vacuum box and allowed to diffuse toward
      the surface. After equilibration, structural features and dynamical properties of
      polymer chains and water in the interfacial domains were analyzed as a function
      of PVA surface concentration at 293 K. Surface pressure values obtained from
      simulations are in agreement with experimental values at corresponding polymer
      specific surface areas. In the explored concentration range of 6-34 MUmol of
      residues/m(2), the chains display a transition between two states. At lower
      surface concentrations, elongated, quite rigid structures are adsorbed on the
      surface, whereas partially submerged globular aggregates, locally covered by thin
      water layers, are formed at higher surface concentrations. At PVA concentrations
      higher than about 20 MUmol of residues/m(2), the percolation of chain aggregates
      over the interface plane produces a surface-confined polymer network with stable
      pores filled by water molecules. A substantial slowing of polymer and water
      dynamics in the interfacial domains is highlighted by the mean squared
      displacement time behavior of terminal residues and the interaction time of PVA
      water hydrogen bonding. The diffusion coefficient of water and lifetime of
      hydrogen bonds between solvent molecules are halved and doubled, respectively, at
      the interface with the highest polymer concentration. The attenuation of water
      and polymer mobility concur to stabilize PVA hydrated networks in contact with
      air. 

PMID- 24877894
TI  - Iptycene-derived crown ether hosts for molecular recognition and self-assembly.
AB  - CONSPECTUS: Synthetic macrocyclic hosts have played key roles in the development
      of host-guest chemistry. Crown ethers are a class of macrocyclic molecules with
      unique flexible structures. They have served as the first generation of synthetic
      hosts, and researchers have extensively studied them in molecular recognition.
      However, the flexible structures of simple crown ethers and their relatively
      limited modes of complexation with guests have limited the further applications
      of these molecules. In recent years, researchers have moved toward fabricating
      interlocking molecules, supramolecular polymers, and other assemblies with
      specific structures and properties. Therefore, researchers have developed more
      complex crown ether-based macrocyclic hosts with multicavity structures and
      multicomplexation modes that provide more diverse and sophisticated host-guest
      systems. In this Account, we summarize our research on the synthesis and
      characterization of iptycene-derived crown ether hosts, their use as host
      molecules, and their applications in self-assembled complexes. Iptycenes
      including triptycenes and pentiptycenes are a class of aromatic compounds with
      unique rigid three-dimensional structures. As a result, they are promising
      building blocks for the synthesis of novel macrocyclic hosts and the construction
      of novel self-assembled complexes with specific structures and properties. During
      the last several years, we have designed and synthesized a new class of iptycene
      derived crown ether hosts including macrotricyclic polyethers, molecular tweezer
      like hosts, and tritopic tris(crown ether) hosts, which are all composed of rigid
      iptycene building blocks linked by flexible crown ether chains. We have examined
      the complexation behavior of these hosts with different types of organic guest
      molecules. Unlike with conventional crown ethers, the combination of iptycene
      moieties and crown ether chains provides the iptycene-derived crown ether hosts
      with complexation properties that differ based on the structure of the guests.
      The rigid iptycene moieties within these synthetic host molecules both maintain
      their inherent three-dimensional cavities and generate multicavity structures.
      The flexible crown ether chains allow the iptycene-derived hosts to adjust their
      conformations as they encapsulate guest molecules. Moreover, the expanded
      complexation properties also allow the host-guest systems based on the iptycene
      derived crown ethers to respond to multiple external stimuli, resulting in a
      variety of supramolecular assemblies. Finally, we also describe the construction
      of mechanically interlocked self-assemblies, molecular switches/molecular
      machines, and supramolecular polymers using these new host molecules. We expect
      that the unique structural features and diverse complexation properties of these
      iptycene-derived crown ether hosts will lead to increasing interest in this field
      and in supramolecular chemistry overall.

PMID- 24877895
TI  - Effect of oxy-combustion flue gas on mercury oxidation.
AB  - This study evaluates the effect of the gases present in a typical oxy-coal
      combustion atmosphere on mercury speciation and compares it with the mercury
      speciation produced in conventional air combustion atmospheres. The work was
      performed at laboratory scale at 150  degrees C. It was found that the minor
      constituents (SO2, NOx, and HCl) significantly modify the percentages of Hg(2+)
      in the gas. The influence of these species on mercury oxidation was demostrated
      when they were tested individually and also when they were blended in different
      gas compositions, although the effect was different to the sum of their
      individual effects. Of the minor constituents, NOx were the main species involved
      in oxidation of mercury. Moreover, it was found that a large concentration of H2O
      vapor also plays an important role in mercury oxidation. Around 50% of the total
      mercury was oxidized in atmospheres with H2O vapor concentrations typical of oxy
      combustion conditions. When the atmospheres have similar concentrations of SO2,
      NO, NO2, HCl, and H2O, the proportion of Hg(0)/Hg(2+) is similar regardless of
      whether CO2 (oxy-fuel combustion) or N2 (air combustion) are the main components
      of the gas. 

PMID- 24877896
TI  - Prevalence of asthma and its association with rhinitis in the elderly.
AB  - BACKGROUND: Asthma and rhinitis are frequent respiratory diseases in children and
      adults. Despite the increase in the aging population, there are few epidemiologic
      data on both diseases in the elderly. So far, no population-based study has
      analyzed the association between asthma and rhinitis symptoms and severity in
      this age group. This study aimed to estimate the prevalence of physician
      diagnosed asthma in the population aged >=65 years in mainland Portugal and to
      evaluate its association with the presence and classification of rhinitis
      according to ARIA recommendations, in this age group. METHODS: A cross-sectional,
      nationwide, population-based survey of individuals aged >=65 years, living in
      mainland Portugal was performed. RESULTS: Data were obtained from 3678
      respondents. The prevalence of physician-diagnosed asthma was 10.9% (95%
      confidence interval (95%CI) 9.9-11.9). The frequency of asthma diagnosis
      increased with the number of nasal symptoms (p < 0.001). A strong association
      between asthma and rhinitis was found (odds ratio (OR) 13.86 (95%CI 10.66
      18.02)). The strength of this association increased with the persistence and
      severity of rhinitis, being particularly high in elderly subjects with moderate
      severe persistent rhinitis (OR 39.9 (95%CI 27.5-58.0)). CONCLUSIONS: Asthma is
      common in the elderly and strongly associated with rhinitis. The OR for asthma is
      especially high in persistent and severe ARIA classification rhinitis types. This
      study strengthens the need for an integrated assessment of asthma together with
      rhinitis in the elderly.

PMID- 24877897
TI  - Interplay between RAS and opioids: opening the Pandora of complexities.
AB  - Angiotensin and endogenous opioids are important bioactive neuropeptides, which
      are widely distributed in the brain and peripheral regions to produce diverse
      biological and neurobiological activities. An endogenous opioid system includes
      proopiomelanocortin-derived enkephalin, dynorphin and endorphin that act on their
      specific receptors such as delta (delta), kappa (kappa) and mu (MU) receptors.
      Research evidence demonstrates significant positive as well as negative
      interactions between renin angiotensin system (RAS) and endogenous opioids in the
      brain and periphery. The diverse actions of Ang II are possibly mediated
      indirectly through endogenous opioids, while opioids are also shown to activate
      RAS components suggesting the up-regulation of each system in concern with each
      other. On the contrary, there are reports suggesting a negative correlation
      between RAS and opioid system. Research evidence also supports the notion that
      Ang II acts as anti-opioid peptide to decrease the actions of opioids. Moreover,
      opioids-induced decline in angiotensin release and functioning has also been
      reported. Co-administration of ACE inhibitors with opioids exhibits significant
      interactions possibly due to decreased metabolism of opioids leading to
      potentiation of their actions. The present review describes the complexities of
      positive and negative interactions between RAS and opioids along with possible
      mechanisms responsible for these interactions.

PMID- 24877898
TI  - Differential sensitivity of ethanol-elicited ERK phosphorylation in nucleus
      accumbens of Sardinian alcohol-preferring and -non preferring rats.
AB  - Sardinian alcohol-preferring (sP) and -non preferring (sNP) rats have been
      selectively bred for opposite ethanol preference and consumption; sP rats
      represent a validated experimental tool to model several aspects of excessive
      ethanol drinking in humans. Phosphorylated Extracellular signal-Regulated Kinase
      (pERK) in dopamine-rich terminal areas plays a critical role in several
      psychopharmacological effects of addictive drugs, including ethanol. This study
      was aimed at investigating whether ethanol-elicited ERK activation may differ in
      key brain areas of ethanol-naive sP and sNP rats. To this end, the effects of
      ethanol (0, 0.5, 1, and 2 g/kg, administered intra-gastrically [i.g.]) on ERK
      phosphorylation were assessed by pERK immunohistochemistry in the shell (AcbSh)
      and core (AcbC) of the nucleus accumbens (Acb) as well as in the prelimbic (PrL)
      and infralimbic (IL) prefrontal cortex (PFCx), in the bed nucleus of stria
      terminalis (BSTL) and in the central nucleus of the amygdala (CeA). Ethanol (1
      g/kg) significantly increased pERK immunoreactivity in AcbSh and AcbC of sP but
      not sNP rats. Conversely, ethanol failed to affect pERK expression in PrL and IL
      PFCx as well as in BSTL and CeA of both sP and sNP rats. These results suggest
      that selective breeding of these rat lines results in differential effects of
      acute ethanol on ERK phosphorylation in brain regions critical for the
      psychopharmacological effects of ethanol.

PMID- 24877899
TI  - Accumulation of modified proteins and aggregate formation in aging.
AB  - Increasing cellular damage during the aging process is considered to be one
      factor limiting the lifespan of organisms. Besides the DNA and lipids, proteins
      are frequent targets of non-enzymatic modifications by reactive substances
      including oxidants and glycating agents. Non-enzymatic protein modifications may
      alter the protein structure often leading to impaired functionality. Although
      proteolytic systems ensure the removal of modified proteins, the activity of
      these proteases was shown to decline during the aging process. The additional age
      related increase of reactive compounds as a result of impaired antioxidant
      systems leads to the accumulation of damaged proteins and the formation of
      protein aggregates. Both, non-enzymatic modified proteins and protein aggregates
      impair cellular functions and tissue properties by a variety of mechanisms. This
      is increasingly important in aging and age-related diseases. In this review, we
      will give an overview on oxidation and glycation of proteins and the function of
      modified proteins in aggregate formation. Furthermore, their effects as well as
      their role in aging and age-related diseases will be highlighted. 

PMID- 24877900
TI  - Comparison of a conventional HIV 1/2 line immunoassay with a rapid confirmatory
      HIV 1/2 assay.
AB  - The performance of the rapid confirmatory HIV 1/2 assay Geenius was compared with
      the conventional HIV 1/2 line immunoblot (INNO-LIA HIV I/II Score). One hundred
      HIV 1/2 confirmed positive samples from donors and patients and 136 negative
      screening samples from blood donors were evaluated with both assays. A 20 member
      performance panel consisting of different HIV 1 and 2 subtypes was also analysed.
      Ninety-nine of the confirmed HIV positive samples were positive with both assays.
      One sample was positive with the INNO-LIA HIV I/II Score but indeterminate with
      the Geenius HIV 1/2. From 136 negative blood donor samples (negative with a combo
      HIV assay and a highly sensitive ID-NAT), 125 were concordant negative. Six and
      five samples were incorrectly indeterminate with the INNO-LIA HIV I/II Score and
      the Geenius HIV 1/2, respectively. One sample was weak positive with the INNO-LIA
      HIV I/II Score but negative with the Geenius HIV 1/2. The 20 member performance
      showed equivalent results with both assays. The rapid assay showed a comparable
      sensitivity and specificity for confirmation for positive and negative HIV donor
      and patient samples as well for a 20 member performance panel. 

PMID- 24877901
TI  - Histopathological characterization and fluorescence in situ hybridization of
      Cyprinid herpesvirus 2 in cultured Prussian carp, Carassius auratus gibelio in
      China.
AB  - Cyprinid herpesvirus 2 (CyHV-2) is an emerging pathogen in the commercially
      exploited fish, Prussian carp (Carassius auratus gibelio), which has caused huge
      economic loss in China and appears to be spreading worldwide. In this article,
      CyHV-2 infection of Prussian carp was confirmed for the first time by polymerase
      chain reaction (PCR), which gave positive results from the tissue samples
      dissected from moribund fish including kidney, spleen, liver, and gill.
      Histological examination showed systemic inflammatory reactions in the infected
      tissues, with infiltration of hemocytes, hypertrophied nuclei, marginal chromatin
      and karyorrhexis, epithelial cell shedding, vacuolar degeneration and focal
      necrosis. Tissue alterations were also evaluated semi-quantitatively by the
      degree of tissue change. The values of degree of tissue change determined for
      kidney, spleen, liver, and gill were significantly greater than respective
      controls and kidney was the most severely damaged organ, with highest degree of
      tissue change value. In addition, a fluorescence in situ hybridization (FISH)
      based on oligonucleotide probes to detect the pathogen directly in the tissue,
      allowing pathogen-lesion correlation, was established. With the advantages of
      better tissue penetration, potentially more specific and stable, three
      oligonucleotide probes were designed. Positive reactions to the probes with
      intense green fluorescence were observed within the infected tissues where PCR
      and H&E analysis had suggested previously the presence of the virus within these
      lesions. The probes did not hybridize with host tissues of uninfected fish, nor
      did they cross-react with 3 other virus samples tested. The current research
      could facilitate the study of CyHV-2 infection mechanism in Prussian carp, and
      enhance the early diagnosis of the novel virus. 

PMID- 24877902
TI  - Patients' quality of life after stopping plasma exchange: a pilot study.
AB  - BACKGROUND: Plasma exchange is being widely used to treat various serious medical
      conditions. There has been very little follow-up data to describe the quality of
      life (QOL) of plasma exchange-recipients after active plasma exchange has
      stopped. OBJECTIVE: To assess the QOL of plasma exchange recipients after
      stopping plasma exchange. METHODS: A pilot study, based on responses to a postal
      questionnaire and clinical data obtained from the patients' charts, was carried
      out. The scores were computed from questionnaire responses and analyzed. RESULTS:
      The response rate was 59% with 58 patients completing a questionnaire three
      months after their final plasma exchange therapy. We identified significant
      heterogeneity in the quality of life of plasma exchange recipients after stopping
      plasma exchange therapy. This could be driven by different patient co
      morbidities. We recommend that during follow up visits, a multi-disciplinary
      approach including consultation with a social worker might be considered for
      patients who may continue to have some limitations in their psychosocial
      activities post-discontinuation of plasma exchange. The high response rate to the
      questionnaire indicates that PLEX patients are interested in being involved in
      QOL studies, which suggests potential support for a prospective study of QOL with
      pre and post questionnaires and more detailed tracking of baseline co
      morbidities.

PMID- 24877903
TI  - A chance to celebrate.

PMID- 24877904
TI  - The challenges of grounded theory.

PMID- 24877905
TI  - The roots and development of constructivist grounded theory.
AB  - AIM: To deconstruct how Charmaz's constructivist grounded theory (CGT) evolved
      from the original ideas of Glaser and Strauss, and to explore how CGT is similar
      to and different from the original grounded theory (GT). BACKGROUND: The origins
      of GT date to 1967 with Glaser and Strauss's study of the treatment of dying
      individuals, applying an inductive method allowing for the development of theory
      without the guidance of a preconceived theory. CGT moves away from the positivism
      of the Glaserian and Straussian GT schools, approaching GT through a
      constructivist lens that addresses how realities are made. DATA SOURCES: This
      article does not involve the collection and analysis of primary data; instead,
      academic literature written by leaders in the field of GT was reviewed to
      generate the ideas presented. REVIEW METHODS: Comprehensive literature review
      drawing on the 'integrative review' principles. DISCUSSION: When selecting a GT
      approach, the possibility of a congruence between the chosen methodology and the
      worldviews of the researcher's discipline and own outlook should be considered.
      CONCLUSION: The differences among the various schools of GT lie in their
      overarching goals and their perspectives of the nature of reality. IMPLICATIONS
      FOR RESEARCH/PRACTICE: Considering the alignment between the constructivist
      worldview and the field of nursing, CGT offers a valuable methodology for
      researchers in this area.

PMID- 24877907
TI  - Using case study research as a rigorous form of inquiry.
AB  - AIM: To describe how case study research (CSR) was used inductively as an all
      encompassing theoretical framework to examine learning in the workplace.
      BACKGROUND: Case study research is a method with strong philosophical
      underpinnings which provides a framework for exploratory research in real-life
      settings ( Yin 2009 ). DATA SOURCES: A study of five students' experiences of
      learning in healthcare environments to explore real-life contexts over the course
      of two years. The study was rich with empirical data, offering a pragmatic
      framework for learning in the workplace. REVIEW METHODS: Observations, interviews
      and documents were used. DISCUSSION: As a result of using CSR, the findings were
      analysed systematically and rigorously. Using multiple methods verified data and
      strengthened the significance of the findings. CONCLUSIONS: This paper focuses on
      the strengths of using the CSR methodology. CSR embraces qualitative research
      methods in a rigorous and systematic manner. CSR has been applied to one example
      of research, addressing each step of the research protocol to use CSR to its full
      potential. IMPLICATIONS FOR PRACTICE/RESEARCH: CSR enables real-life settings to
      be studied systematically and rigorously, offering examples of practice in
      nursing and education.

PMID- 24877906
TI  - Challenges in combining different data sets during analysis when using grounded
      theory.
AB  - AIM: To describe the challenges in combining two data sets during grounded theory
      analysis. BACKGROUND: The use of grounded theory in nursing research is common.
      It is a suitable method for studying human action and interaction. It is
      recommended that many alternative sources of data are collected to create as rich
      a dataset as possible. DATA SOURCES: Data from interviews with people with
      diabetes (n=19) and their family members (n=19). REVIEW METHODS: Combining two
      data sets. DISCUSSION: When using grounded theory, there are numerous challenges
      in collecting and managing data, especially for the novice researcher. One
      challenge is to combine different data sets during the analysis. There are many
      methodological textbooks about grounded theory but there is little written in the
      literature about combining different data sets. CONCLUSION: Discussion is needed
      on the management of data and the challenges of grounded theory. IMPLICATIONS FOR
      RESEARCH/PRACTICE: This article provides a means for combining different data
      sets in the grounded theory analysis process.

PMID- 24877908
TI  - Conducting qualitative research in the context of pre-existing peer and collegial
      relationships.
AB  - AIM: To highlight issues and challenges faced in recruitment and interviewing
      during a study that sought to explore the transition of nurses into academic life
      and the associated ethical implications. BACKGROUND: This paper explores the
      challenges faced in conducting research where the potential participants are
      peers and workplace colleagues. There are advantages when conducting research
      with those among whom a pre-existing relationship is shared. However,
      difficulties can also arise. REVIEW METHODS: A methodological review was
      undertaken. Key database searches included CINAHL, MEDLINE, PubMed, Scopus and
      Google Scholar using the keywords as search terms. Studies were included if they
      described in detail issues surrounding qualitative interviewing of peers and
      colleagues. DISCUSSION: Management of the issues involved is discussed, with
      emphasis on boundaries, trust and rapport, the use of self-disclosure and
      maintaining confidentiality. CONCLUSION: Research involving peers and colleagues
      has received relatively little consideration in the literature. There are
      difficulties associated with interviewing participants with whom the researcher
      has a pre-existing and ongoing relationship in the same organisation. To ensure
      ethical conduct, strategies can be used to mitigate negative situations such as
      issues surrounding dual roles, practising reflexivity, trust and rapport, self
      disclosure and confidentiality. IMPLICATIONS FOR RESEARCH/PRACTICE: It is
      imperative that dual roles are declared and acknowledged. Researchers need to be
      mindful of the difficulties that may occur and prioritise participants'
      confidentiality and privacy.

PMID- 24877909
TI  - An introduction to the biographical narrative interpretive method.
AB  - AIM: To introduce the biographical narrative interpretive method (BNIM) to nurse
      researchers in search of a new methodology and method. BACKGROUND: Listening to
      and interpreting the narratives of patients is a core feature of nursing.
      Research methodologies and methods frequently do not fully take into account the
      historical, psycho-social and biographical dynamics of people's lives. DATA
      SOURCES: This paper draws from the experiences of both authors who have
      previously utilised the BNIM method, as well as sourcing relevant literature.
      REVIEW METHODS: This is a methodology paper that reviews the historical context
      of BNIM and provides an overview of its potential application for nursing
      research. Discussion The core assumptions and analytic strategy of BNIM focus on
      three inter-related facets: the person's whole life history or story (biography),
      how they tell it (narrative) and the social interpretation (interpretive). BNIM
      uses a unique interviewing technique to elicit an uninterrupted story from
      participants. The BNIM analytic tool is formulaic and uses nine stages to analyse
      individual cases. A tenth stage helps with analysis across cases. CONCLUSION:
      BNIM methodology and methods empower participants to articulate the vicissitudes
      of their life and experiences of illness while also providing the researcher with
      a framework for data analysis and interpretation to give meaning to individuals'
      life stories. IMPLICATIONS FOR RESEARCH/PRACTICE: The BNIM interview technique
      and analytic framework are useful tools to help with an in-depth qualitative
      exploration of life stories in context.

PMID- 24877910
TI  - Adapting qualitative research strategies to technology savvy adolescents.
AB  - AIM: To adapt research strategies involving adolescents in a grounded theory
      qualitative research study by conducting email rather than face-to-face
      interviews. BACKGROUND: Adolescent culture relies heavily on text-based
      communication and teens prefer interactions mediated through technology.
      Traditional qualitative research strategies need to be rethought when working
      with adolescents. Adapting interviewing strategies to electronic environments is
      timely and relevant for researching adolescents. DATA SOURCES: Twenty three
      adolescents (aged 16-21) were interviewed by email. A letter of invitation was
      distributed. Potential participants emailed the researcher to convey interest in
      participating. If the inclusion criteria were met, email interviews were
      initiated. Participants controlled the interviews through their rate of response
      to interview questions. REVIEW METHODS: A grounded theory methodology was
      employed. Initial contact with participants reiterated confidentiality and the
      ability to withdraw from the study at any time. Interviews began with the
      collection of demographic information and a broad opening based on a semi
      structured interview guide. All data were permissible, including text, photos,
      music, videos or outside media, for example YouTube. The participant was allowed
      to give direction to the interview after initial questions were posed. Email
      interviews continued until saturation was reached in the data. DISCUSSION:
      Participants were enthusiastic about email interviewing. Attrition did not occur.
      Email interviewing gave participants more control over the research, decreased
      power differentials between the adolescent and researcher, allowed the study to
      be adapted to cultural, linguistic and developmental needs, and maintained
      confidentiality. CONCLUSION: As participants said that email communication was
      slow and they preferred instant messaging, replication in faster-paced media is
      recommended. Repetition in face-to-face settings is warranted to evaluate how
      technology may have influenced the findings. Implications for practice/research
      Adolescents' use of the internet and their preference for textbased communication
      makes a compelling support for modifying traditional face-to-face qualitative
      investigations to reflect these changing contextual conditions.

PMID- 24877914
TI  - The contribution our research makes to care.

PMID- 24877917
TI  - Observation of the second triatomic resonance in Efimov's scenario.
AB  - We report the observation of a three-body recombination resonance in an ultracold
      gas of cesium atoms at a very large negative value of the s-wave scattering
      length. The resonance is identified as the second triatomic Efimov resonance,
      which corresponds to the situation where the first excited Efimov state appears
      at the threshold of three free atoms. This observation, together with a finite
      temperature analysis and the known first resonance, allows the most accurate
      demonstration to date of the discrete scaling behavior at the heart of Efimov
      physics. For the system of three identical bosons, we obtain a scaling factor of
      21.0(1.3), close to the ideal value of 22.7. 

PMID- 24877918
TI  - Probing macroscopic realism via Ramsey correlation measurements.
AB  - We describe a new and experimentally feasible protocol for performing fundamental
      tests of quantum mechanics with massive objects. In our approach, a single two
      level system is used to probe the motion of a nanomechanical resonator via
      multiple Ramsey interference measurements. This scheme enables the measurement of
      modular variables of macroscopic continuous-variable systems; we show that
      correlations thereof violate a Leggett-Garg inequality and can be applied for
      tests of quantum contextuality. Our method can be implemented with a variety of
      different solid-state or photonic qubit-resonator systems, and it provides a
      clear experimental signature to distinguish the predictions of quantum mechanics
      from those of other alternative theories at a macroscopic scale. 

PMID- 24877919
TI  - Heisenberg-limited atom clocks based on entangled qubits.
AB  - We present a quantum-enhanced atomic clock protocol based on groups of
      sequentially larger Greenberger-Horne-Zeilinger (GHZ) states that achieves the
      best clock stability allowed by quantum theory up to a logarithmic correction.
      Importantly the protocol is designed to work under realistic conditions where the
      drift of the phase of the laser interrogating the atoms is the main source of
      decoherence. The simultaneous interrogation of the laser phase with a cascade of
      GHZ states realizes an incoherent version of the phase estimation algorithm that
      enables Heisenberg-limited operation while extending the coherent interrogation
      time beyond the laser noise limit. We compare and merge the new protocol with
      existing state of the art interrogation schemes, and identify the precise
      conditions under which entanglement provides an advantage for clock
      stabilization: it allows a significant gain in the stability for short averaging
      time. 

PMID- 24877920
TI  - Hamiltonian learning and certification using quantum resources.
AB  - In recent years quantum simulation has made great strides, culminating in
      experiments that existing supercomputers cannot easily simulate. Although this
      raises the possibility that special purpose analog quantum simulators may be able
      to perform computational tasks that existing computers cannot, it also introduces
      a major challenge: certifying that the quantum simulator is in fact simulating
      the correct quantum dynamics. We provide an algorithm that, under relatively weak
      assumptions, can be used to efficiently infer the Hamiltonian of a large but
      untrusted quantum simulator using a trusted quantum simulator. We illustrate the
      power of this approach by showing numerically that it can inexpensively learn the
      Hamiltonians for large frustrated Ising models, demonstrating that quantum
      resources can make certifying analog quantum simulators tractable. 

PMID- 24877921
TI  - Optimal quantum control of multimode couplings between trapped ion qubits for
      scalable entanglement.
AB  - We demonstrate entangling quantum gates within a chain of five trapped ion qubits
      by optimally shaping optical fields that couple to multiple collective modes of
      motion. We individually address qubits with segmented optical pulses to construct
      multipartite entangled states in a programmable way. This approach enables high
      fidelity gates that can be scaled to larger qubit registers for quantum
      computation and simulation. 

PMID- 24877922
TI  - Experimental demonstration of polarization encoding measurement-device
      independent quantum key distribution.
AB  - We demonstrate the first implementation of polarization encoding measurement
      device-independent quantum key distribution (MDI-QKD), which is immune to all
      detector side-channel attacks. Active phase randomization of each individual
      pulse is implemented to protect against attacks on imperfect sources. By
      optimizing the parameters in the decoy state protocol, we show that it is
      feasible to implement polarization encoding MDI-QKD with commercial off-the-shelf
      devices. A rigorous finite key analysis is applied to estimate the secure key
      rate. Our work paves the way for the realization of a MDI-QKD network, in which
      the users only need compact and low-cost state-preparation devices and can share
      complicated and expensive detectors provided by an untrusted network server. 

PMID- 24877924
TI  - Nonmodal linear stability of the Schwarzschild black hole.
AB  - A proof is given that the space L of solutions of the linearized vacuum Einstein
      equation around a Schwarzschild black hole is parametrized by two scalar fields,
      which are gauge invariant combinations of perturbed algebraic and differential
      invariants of the Weyl tensor and encode the information on the odd (-) and even
      (+) sectors L +/-. These fields measure the distortion of the geometry caused by
      a generic perturbation and are shown to be pointwise bounded on the outer region
      r >= 2M.

PMID- 24877923
TI  - Fast accurate state measurement with superconducting qubits.
AB  - Faster and more accurate state measurement is required for progress in
      superconducting qubit experiments with greater numbers of qubits and advanced
      techniques such as feedback. We have designed a multiplexed measurement system
      with a bandpass filter that allows fast measurement without increasing
      environmental damping of the qubits. We use this to demonstrate simultaneous
      measurement of four qubits on a single superconducting integrated circuit, the
      fastest of which can be measured to 99.8% accuracy in 140 ns. This accuracy and
      speed is suitable for advanced multiqubit experiments including surface-code
      error correction.

PMID- 24877925
TI  - How much can we learn about the physics of inflation?
AB  - The recent BICEP2 measurement of B modes in the polarization of the cosmic
      microwave background suggests that inflation was driven by a field at an energy
      scale of 2 * 10(16) GeV. I explore the potential of upcoming cosmic microwave
      radiation polarization experiments to further constrain the physics underlying
      inflation. If the signal is confirmed, then two sets of experiments covering a
      large area will shed light on inflation. Low-resolution measurements can pin down
      the tensor to scalar ratio at the percent level, thereby distinguishing models
      from one another. A high angular resolution experiment will be necessary to
      measure the tilt of the tensor spectrum, testing the consistency relation that
      relates the tilt to the amplitude.

PMID- 24877926
TI  - Inflationary tensor perturbations after BICEP2.
AB  - The measurement of B-mode polarization of the cosmic microwave background at
      large angular scales by the BICEP experiment suggests a stochastic gravitational
      wave background from early-Universe inflation with a surprisingly large
      amplitude. The power spectrum of these tensor perturbations can be probed both
      with further measurements of the microwave background polarization at smaller
      scales and also directly via interferometry in space. We show that sufficiently
      sensitive high-resolution B-mode measurements will ultimately have the ability to
      test the inflationary consistency relation between the amplitude and spectrum of
      the tensor perturbations, confirming their inflationary origin. Additionally, a
      precise B-mode measurement of the tensor spectrum will predict the tensor
      amplitude on solar system scales to 20% accuracy for an exact power-law tensor
      spectrum, so a direct detection will then measure the running of the tensor
      spectral index to high precision. 

PMID- 24877927
TI  - Can primordial magnetic fields be the origin of the BICEP2 data?
AB  - If the B-mode signal in the cosmic microwave background polarization seen by the
      BICEP2 experiment is confirmed, it has dramatic implications for models of
      inflation. The result is also in tension with Planck limits on standard
      inflationary models. It is, therefore, important to investigate whether this
      signal can arise from alternative sources. If so, this could lessen the pressure
      on inflationary models and the tension with Planck data. We investigate whether
      vector and tensor modes from primordial magnetic fields can explain the signal.
      We find that, in principle, magnetic fields generated during inflation can indeed
      produce the required B mode, for a suitable range of energy scales of inflation.
      In this case, the primordial gravitational wave amplitude is negligible, so that
      there is no tension with Planck and no problems posed for current inflationary
      models. However, the simplest magnetic model is in tension with Planck limits on
      non-Gaussianity in the trispectrum. It may be possible to fine tune the
      magnetogenesis model so that this non-Gaussianity is suppressed. Alternatively, a
      weaker magnetic field can pass the non-Gaussianity constraints and allow the
      primordial tensor mode to be reduced to r ? 0.09, thus removing the tension with
      Planck data and alleviating the problems with simple inflationary models.

PMID- 24877928
TI  - New constraints on dark matter effective theories from standard model loops.
AB  - We consider an effective field theory for a gauge singlet Dirac dark matter
      particle interacting with the standard model fields via effective operators
      suppressed by the scale Lambda ? 1 TeV. We perform a systematic analysis of the
      leading loop contributions to spin-independent Dirac dark matter-nucleon
      scattering using renormalization group evolution between Lambda and the low
      energy scale probed by direct detection experiments. We find that electroweak
      interactions induce operator mixings such that operators that are naively
      velocity suppressed and spin dependent can actually contribute to spin
      independent scattering. This allows us to put novel constraints on Wilson
      coefficients that were so far poorly bounded by direct detection. Constraints
      from current searches are already significantly stronger than LHC bounds, and
      will improve in the near future. Interestingly, the loop contribution we find is
      isospin violating even if the underlying theory is isospin conserving.

PMID- 24877929
TI  - Combined analysis of nuMU disappearance and nuMU->nue appearance in MINOS using
      accelerator and atmospheric neutrinos.
AB  - We report on a new analysis of neutrino oscillations in MINOS using the complete
      set of accelerator and atmospheric data. The analysis combines the nu(MU)
      disappearance and nu(e) appearance data using the three-flavor formalism. We
      measure |Deltam(32)(2)| = [2.28-2.46] * 10(-3) eV(2) (68% C.L.) and
      sin(2)theta(23) = 0.35-0.65 (90% C.L.) in the normal hierarchy, and
      |Deltam(32)(2)| = [2.32-2.53] * 10(-3) eV(2) (68% C.L.) and sin(2)theta(23) =
      0.34-0.67 (90% C.L.) in the inverted hierarchy. The data also constrain
      delta(CP), the theta(23} octant degeneracy and the mass hierarchy; we disfavor
      36% (11%) of this three-parameter space at 68% (90%) C.L.

PMID- 24877931
TI  - Natural Higgs mass in supersymmetry from nondecoupling effects.
AB  - The Higgs mass implies fine-tuning for minimal theories of weak-scale
      supersymmetry (SUSY). Nondecoupling effects can boost the Higgs mass when new
      states interact with the Higgs boson, but new sources of SUSY breaking that
      accompany such extensions threaten naturalness. We show that two singlets with a
      Dirac mass can increase the Higgs mass while maintaining naturalness in the
      presence of large SUSY breaking in the singlet sector. We explore the modified
      Higgs phenomenology of this scenario, which we call the "Dirac next-to-minimal
      supersymmetric standard model." 

PMID- 24877932
TI  - Noncommuting momenta of topological solitons.
AB  - We show that momentum operators of a topological soliton may not commute among
      themselves when the soliton is associated with the second cohomology H2 of the
      target space. The commutation relation is proportional to the winding number,
      taking a constant value within each topological sector. The noncommutativity
      makes it impossible to specify the momentum of a topological soliton, and induces
      a Magnus force.

PMID- 24877934
TI  - Laser-nucleus reactions: population of states far above yrast and far from
      stability.
AB  - Nuclear reactions induced by a strong zeptosecond laser pulse are studied
      theoretically in the quasiadiabatic regime where the photon absorption rate is
      comparable to the nuclear equilibration rate. We find that multiple photon
      absorption leads to the formation of a compound nucleus in the so-far unexplored
      regime of excitation energies several hundred MeV above the yrast line. At these
      energies, further photon absorption is limited by neutron decay and/or induced
      nucleon emission. With a laser pulse of ~ 50 zs duration, proton-rich nuclei far
      off the line of stability are produced.

PMID- 24877933
TI  - Novel method to study neutron capture of 235U and 238U simultaneously at keV
      energies.
AB  - The neutron capture cross sections of the main uranium isotopes, (235)U and
      (238)U, were measured simultaneously for keV energies, for the first time by
      combining activation technique and atom counting of the reaction products using
      accelerator mass spectrometry. New data, with a precision of 3%-5%, were obtained
      from mg-sized natural uranium samples for neutron energies with an equivalent
      Maxwell-Boltzmann distribution of kT ~ 25 keV and for a broad energy distribution
      peaking at 426 keV. The cross-section ratio of (235)U(n,gamma)/(238)U(n,gamma)
      can be deduced in accelerator mass spectrometry directly from the atom ratio of
      the reaction products (236)U/(239)U, independent of any fluence normalization.
      Our results confirm the values at the lower band of existing data. They serve as
      important anchor points to resolve present discrepancies in nuclear data
      libraries as well as for the normalization of cross-section data used in the
      nuclear astrophysics community for s-process studies.

PMID- 24877936
TI  - Enhanced one-photon double ionization of atoms and molecules in an environment of
      different species.
AB  - The correlated nature of electronic states in atoms and molecules is manifested
      in the simultaneous emission of two electrons after absorption of a single photon
      close to the respective threshold. Numerous observations in atoms and small
      molecules demonstrate that the double ionization efficiency close to threshold is
      rather small. In this Letter we show that this efficiency can be dramatically
      enhanced in the environment. To be specific, we concentrate on the case where the
      species in question has one or several He atoms as neighbors. The enhancement is
      achieved by an indirect process, where a He atom of the environment absorbs a
      photon and the resulting He(+) cation is neutralized fast by a process known as
      electron transfer mediated decay, producing thereby doubly ionized species. The
      enhancement of the double ionization is demonstrated in detail for the example of
      the Mg . He cluster. We show that the double ionization cross section of Mg
      becomes 3 orders of magnitude larger than the respective cross section of the
      isolated Mg atom. The impact of more neighbors is discussed and the extension to
      other species and environments is addressed.

PMID- 24877935
TI  - Measurements of fusion reactions of low-intensity radioactive carbon beams on 12C
      and their implications for the understanding of X-ray bursts.
AB  - The interaction between neutron-rich nuclei plays an important role for
      understanding the reaction mechanism of the fusion process as well as for the
      energy production through pycnonuclear reactions in the crust of neutron stars.
      We have performed the first measurements of the total fusion cross sections in
      the systems (10,14,15)C+(12)C using a new active target-detector system. In the
      energy region accessible with existing radioactive beams, a good agreement
      between the experimental and theoretical cross sections is observed. This gives
      confidence in our ability to calculate fusion cross sections for systems which
      are outside the range of today's radioactive beam facilities.

PMID- 24877937
TI  - Subcycle control of electron-electron correlation in double ionization.
AB  - Double ionization of neon with orthogonally polarized two-color (OTC) laser
      fields is investigated using coincidence momentum imaging. We show that the two
      electron emission dynamics in nonsequential double ionization can be controlled
      by tuning the subcycle shape of the electric field of the OTC pulses. We
      demonstrate experimentally switching from correlated to anticorrelated two
      electron emission, and control over the directionality of the two-electron
      emission. Simulations based on a semiclassical trajectory model qualitatively
      explain the experimental results by a subcycle dependence of the electron
      recollision time on the OTC field shape. 

PMID- 24877938
TI  - Interaction-induced quantum phase revivals and evidence for the transition to the
      quantum chaotic regime in 1D atomic Bloch oscillations.
AB  - We study atomic Bloch oscillations in an ensemble of one-dimensional tilted
      superfluids in the Bose-Hubbard regime. For large values of the tilt, we observe
      interaction-induced coherent decay and matter-wave quantum phase revivals of the
      Bloch oscillating ensemble. We analyze the revival period dependence on
      interactions by means of a Feshbach resonance. When reducing the value of the
      tilt, we observe the disappearance of the quasiperiodic phase revival signature
      towards an irreversible decay of Bloch oscillations, indicating the transition
      from regular to quantum chaotic dynamics. 

PMID- 24877939
TI  - Far-field signatures of a two-body bound state in collective emission from
      interacting two-level atoms on a lattice.
AB  - The collective emission from a one-dimensional chain of interacting two-level
      atoms is investigated. We calculate the light scattered by dissipative few
      excitation eigenstates in the far field, and, in particular, focus on signatures
      of a lattice two-body bound state. We present analytical results for the angle
      resolved, temporal decay of the scattered light intensity. Moreover, we find that
      the steady-state emission spectrum that emerges when the system is probed by a
      weak, incoherent driving field exhibits a distinct signature for the existence of
      a bound state, and allows us to determine the momentum distribution of the two
      body relative wave function. Intriguingly, our study does not rely on single-atom
      addressability and/or manipulation techniques. 

PMID- 24877940
TI  - Nature of spatiotemporal light bullets in bulk Kerr media.
AB  - We present a detailed experimental investigation which uncovers the nature of
      light bullets generated from self-focusing in a bulk dielectric medium with Kerr
      nonlinearity in the anomalous group velocity dispersion regime. By high dynamic
      range measurements of three-dimensional intensity profiles, we demonstrate that
      the light bullets consist of a sharply localized high-intensity core, which
      carries the self-compressed pulse and contains approximately 25% of the total
      energy, and a ring-shaped spatiotemporal periphery. Subdiffractive propagation
      along with dispersive broadening of the light bullets in free space after they
      exit the nonlinear medium indicate a strong space-time coupling within the
      bullet. This finding is confirmed by measurements of a spatiotemporal energy
      density flux that exhibits the same features as a stationary, polychromatic
      Bessel beam, thus highlighting the nature of the light bullets. 

PMID- 24877942
TI  - Anomalous light absorption around subwavelength apertures in metal films.
AB  - In this Letter, we study the heat dissipated at metal surfaces by the
      electromagnetic field scattered by isolated subwavelength apertures in metal
      screens. In contrast to the common belief that the intensity of waves created by
      local sources should decrease with the distance from the sources, we reveal that
      the dissipated heat at the surface remains constant over a broad spatial
      interval. This behavior that occurs for noble metals at near infrared wavelengths
      is observed with nonintrusive thermoreflectance measurements and is explained
      with an analytical model, which underlines the intricate role played by
      quasicylindrical waves in the phenomenon. Additionally, we show that, by
      monitoring the phase of the quasicylindrical waves, the total heat dissipated at
      the metal surface can be rendered substantially smaller than the heat dissipated
      by the launched plasmon. This interesting property offers an alternative to
      amplification for overcoming the loss issue in miniaturized plasmonic devices. 

PMID- 24877941
TI  - Observation of migrating transverse Anderson localizations of light in nonlocal
      media.
AB  - We report the experimental observation of the interaction and attraction of many
      localized modes in a two-dimensional system realized by a disordered optical
      fiber supporting transverse Anderson localization. We show that a nonlocal
      optically nonlinear response of thermal origin alters the localization length by
      an amount determined by the optical power and also induces an action at a
      distance between the localized modes and their spatial migration. Evidence of a
      collective and strongly interacting regime is given. 

PMID- 24877943
TI  - Long-term evolution of broken wakefields in finite-radius plasmas.
AB  - A novel effect of fast heating and charging a finite-radius plasma is discovered
      in the context of plasma wakefield acceleration. As the plasma wave breaks, most
      of its energy is transferred to plasma electrons. The electrons gain substantial
      transverse momentum and escape the plasma radially, which gives rise to a strong
      charge-separation electric field and azimuthal magnetic field around the plasma.
      The slowly varying field structure is preserved for hundreds of wakefield periods
      and contains (together with hot electrons) up to 80% of the initial wakefield
      energy. 

PMID- 24877945
TI  - Three-component ultracold Fermi gases with spin-orbit coupling.
AB  - We investigate the pairing physics in a three-component Fermi-Fermi mixture,
      where a few fermionic impurities are immersed in a noninteracting two-component
      Fermi gas with synthetic spin-orbit coupling (SOC), and interact attractively
      with one spin species in the Fermi gas. Because of the interplay of SOC and the
      spin-selective interaction, the molecular state intrinsically acquires a nonzero
      center-of-mass momentum, which results in a new type of Fulde-Ferrell (FF)
      pairing in spin-orbit coupled Fermi systems. The existence of the Fermi sea can
      also lead to the competition between FF-like molecular states with different
      center-of-mass momenta, which corresponds to a first-order transition between FF
      phases in the thermodynamic limit. As the interaction strength is tuned, a
      polaron-molecule transition occurs in the highly imbalanced system, where the
      boundary varies nonmonotonically with SOC parameters and gives rise to the
      reentrance of polaron states. The rich physics in this system can be probed using
      existing experimental techniques. 

PMID- 24877944
TI  - 2D X-ray radiography of imploding capsules at the national ignition facility.
AB  - First measurements of the in-flight shape of imploding inertial confinement
      fusion (ICF) capsules at the National Ignition Facility (NIF) were obtained by
      using two-dimensional x-ray radiography. The sequence of area-backlit, time-gated
      pinhole images is analyzed for implosion velocity, low-mode shape and density
      asymmetries, and the absolute offset and center-of-mass velocity of the capsule
      shell. The in-flight shell is often observed to be asymmetric even when the
      concomitant core self-emission is round. A ~ 15 MUm shell asymmetry amplitude of
      the Y(40) spherical harmonic mode was observed for standard NIF ICF hohlraums at
      a shell radius of ~ 200 MUm (capsule at ~ 5* radial compression). This asymmetry
      is mitigated by a ~ 10% increase in the hohlraum length.

PMID- 24877946
TI  - Driving ordering processes in molecular-dynamics simulations.
AB  - Self-organized criticality describes the emergence of complexity in dynamical
      nonequilibrium systems. In this paper we introduce a unique approach whereby a
      driven energy conversion is utilized as a sampling bias for ordered arrangements
      in molecular dynamics simulations of atomic and molecular fluids. This approach
      gives rise to dramatically accelerated nucleation rates, by as much as 30 orders
      of magnitude, without the need of predefined order parameters, which commonly
      employed rare-event sampling methods rely on. The measured heat fluxes suggest
      how the approach can be generalized. 

PMID- 24877947
TI  - Frozen topology: entanglements control nucleation and crystallization in
      polymers.
AB  - Polymer chains form lamellar structures during crystallization which display a
      memory of thermal history. Using molecular dynamics simulations and primitive
      path analysis, we show a direct dependence of both density and crystalline stem
      length on the local entanglement length. The slow relaxation of the entanglement
      state after a change of external conditions can directly explain the role of
      thermal history for polymer crystallization, in particular memory effects. The
      analysis of the local entanglement state can be used to predict the occurrence of
      nucleation events. Our results present a fresh insight of the nonequilibrium
      properties of polymer crystals which might be identified as "frozen topology" of
      polymer melts. 

PMID- 24877948
TI  - Metastable states and wetting transition of submerged superhydrophobic
      structures.
AB  - Superhydrophobicity on structured surfaces is frequently achieved via the
      maintenance of liquid-air interfaces adjacent to the trapped air pockets. These
      interfaces, however, are subject to instabilities due to the Cassie-Baxter-to
      Wenzel transition and total wetting. The current work examines in situ liquid-air
      interfaces on a submerged surface patterned with cylindrical micropores using
      confocal microscopy. Both the pinned Cassie-Baxter and depinned metastable states
      are directly observed and measured. The metastable state dynamically evolves,
      leading to a transition to the Wenzel state. This process is extensively
      quantified under different ambient pressure conditions, and the data are in good
      agreement with a diffusion-based model prediction. A similarity law along with a
      characteristic time scale is derived which governs the lifetime of the air
      pockets and which can be used to predict the longevity of underwater
      superhydrophobicity.

PMID- 24877949
TI  - TiO2/ferroelectric heterostructures as dynamic polarization-promoted catalysts
      for photochemical and electrochemical oxidation of water.
AB  - Using first-principles density functional theory calculations, we explore the
      chemical activity of epitaxial heterostructures of TiO2 anatase on strained polar
      SrTiO3 films focusing on the oxygen evolution reaction (OER), the bottleneck of
      water splitting. Our results show that the reactivity of the TiO2 surface is
      tuned by electric dipoles dynamically induced by the adsorbed species during the
      intermediate steps of the reaction while the initial and final steps remain
      unaffected. Compared to the OER on unsupported TiO2, the combined effects of the
      dynamically induced dipoles and epitaxial strain strongly reduce rate-limiting
      thermodynamic barriers and significantly improve the efficiency of the reaction.

PMID- 24877950
TI  - Atomic monolayer deposition on the surface of nanotube mechanical resonators.
AB  - We study monolayers of noble gas atoms (Xe, Kr, Ar, and Ne) deposited on
      individual ultraclean suspended nanotubes. For this, we record the resonance
      frequency of the mechanical motion of the nanotube, since it provides a direct
      measure of the coverage. The latter is the number of adsorbed atoms divided by
      the number of the carbon atoms of the suspended nanotube. Monolayers form when
      the temperature is lowered in a constant pressure of noble gas atoms. The
      coverage of Xe monolayers remains constant at 1/6 over a large temperature range.
      This finding reveals that Xe monolayers are solid phases with a triangular atomic
      arrangement, and are commensurate with the underlying carbon nanotube. By
      comparing our measurements to theoretical calculations, we identify the phases of
      Ar and Ne monolayers as fluids, and we tentatively describe Kr monolayers as
      solid phases. These results underscore that mechanical resonators made from
      single nanotubes are excellent probes for surface science. 

PMID- 24877951
TI  - Density-functional theory of thermoelectric phenomena.
AB  - We introduce a nonequilibrium density-functional theory of local temperature and
      associated local energy density that is suited for the study of thermoelectric
      phenomena. The theory rests on a local temperature field coupled to the energy
      density operator. We identify the excess-energy density, in addition to the
      particle density, as the basic variable, which is reproduced by an effective
      noninteracting Kohn-Sham system. A novel Kohn-Sham equation emerges featuring a
      time-dependent and spatially varying mass which represents local temperature
      variations. The adiabatic contribution to the Kohn-Sham potentials is related to
      the entropy viewed as a functional of the particle and energy density.
      Dissipation can be taken into account by employing linear response theory and the
      thermoelectric transport coefficients of the electron gas. 

PMID- 24877952
TI  - From infinite to two dimensions through the functional renormalization group.
AB  - We present a novel scheme for an unbiased, nonperturbative treatment of strongly
      correlated fermions. The proposed approach combines two of the most successful
      many-body methods, the dynamical mean field theory and the functional
      renormalization group. Physically, this allows for a systematic inclusion of
      nonlocal correlations via the functional renormalization group flow equations,
      after the local correlations are taken into account nonperturbatively by the
      dynamical mean field theory. To demonstrate the feasibility of the approach, we
      present numerical results for the two-dimensional Hubbard model at half filling. 

PMID- 24877953
TI  - Qubits based on polariton Rabi oscillators.
AB  - We propose a novel physical mechanism for the creation of long-lived macroscopic
      exciton-photon qubits in semiconductor microcavities with embedded quantum wells
      in the strong coupling regime. The polariton qubit is a superposition of lower
      branch and upper branch exciton-polariton states. We argue that the coherence
      time of Rabi oscillations can be dramatically enhanced due to their stimulated
      pumping from a permanent thermal reservoir of polaritons. We discuss applications
      of such qubits for quantum information processing, cloning, and storage purposes.

PMID- 24877954
TI  - Characterization of a topological Mott insulator in one dimension.
AB  - We investigate properties of a topological Mott insulator in one dimension by
      examining the bulk topological invariant and the entanglement spectrum of a
      correlated electron model. We clarify how gapless edge states in a noninteracting
      topological band insulator evolve into spinon edge states in a topological Mott
      insulator. Furthermore, we propose a topological Mott transition, which is a new
      type of topological phase transition which has never been observed in free
      fermion systems. This unconventional transition occurs in spin liquid phases in
      the Mott insulator and is accompanied by zeros of the single-electron Green's
      function and a gap closing in the spin excitation spectrum. 

PMID- 24877955
TI  - Selective equilibration of spin-polarized quantum Hall edge states in graphene.
AB  - We report on transport measurements of dual-gated, single-layer graphene devices
      in the quantum Hall regime, allowing for independent control of the filling
      factors in adjoining regions. Progress in device quality allows us to study
      scattering between edge states when the fourfold degeneracy of the Landau level
      is lifted by electron correlations, causing edge states to be spin and/or valley
      polarized. In this new regime, we observe a dramatic departure from the
      equilibration seen in more disordered devices: edge states with opposite spins
      propagate without mixing. As a result, the degree of equilibration inferred from
      transport can reveal the spin polarization of the ground state at each filling
      factor. In particular, the first Landau level is shown to be spin polarized at
      half filling, providing an independent confirmation of a conclusion of Young et
      al. [Nat. Phys. 8, 550 (2012). The conductance in the bipolar regime is strongly
      suppressed, indicating that copropagating edge states, even with the same spin,
      do not equilibrate along PN interfaces. We attribute this behavior to the
      formation of an insulating nu = 0 stripe at the PN interface.

PMID- 24877956
TI  - Emergence of massless Dirac fermions in graphene's Hofstadter butterfly at
      switches of the quantum Hall phase connectivity.
AB  - The fractal spectrum of magnetic minibands (Hofstadter butterfly), induced by the
      moire superlattice of graphene on a hexagonal crystal substrate, is known to
      exhibit gapped Dirac cones. We show that the gap can be closed by slightly
      misaligning the substrate, producing a hierarchy of conical singularities (Dirac
      points) in the band structure at rational values Phi = (p/q)(h/e) of the magnetic
      flux per supercell. Each Dirac point signals a switch of the topological quantum
      number in the connected component of the quantum Hall phase diagram. Model
      calculations reveal the scale-invariant conductivity sigma = 2qe(2)/pih and Klein
      tunneling associated with massless Dirac fermions at these connectivity switches.

PMID- 24877957
TI  - First principles explanation of the positive Seebeck coefficient of lithium.
AB  - Lithium is one of the simplest metals, with negative charge carriers and a close
      reproduction of free-electron dispersion. Experimentally, however, Li is one of a
      handful of elemental solids (along with Cu, Ag, and Au) where the sign of the
      Seebeck coefficient (S) is opposite to that of the carrier. This counterintuitive
      behavior still lacks a satisfactory interpretation. We calculate S fully from
      first principles, within the framework of Allen's formulation of Boltzmann
      transport theory. Here it is crucial to avoid the constant relaxation time
      approximation, which gives a sign for S which is necessarily that of the
      carriers. Our calculated S are in excellent agreement with experimental data, up
      to the melting point. In comparison with another alkali metal, Na, we demonstrate
      that within the simplest nontrivial model for the energy dependency of the
      electron lifetimes, the rapidly increasing density of states (DOS) across the
      Fermi energy is related to the sign of S in Li. The exceptional energy dependence
      of the DOS is beyond the free-electron model, as the dispersion is distorted by
      the Brillouin zone edge; this has a stronger effect in Li than other alkali
      metals. The electron lifetime dependency on energy is central, but the details of
      the electron-phonon interaction are found to be less important, contrary to what
      has been believed for several decades. Band engineering combined with the
      mechanism exposed here may open the door to new "ambipolar" thermoelectric
      materials, with a tunable sign for the thermopower even if either n- or p-type
      doping is impossible. 

PMID- 24877958
TI  - Transport properties of a 3D topological insulator based on a strained high
      mobility HgTe film.
AB  - We investigate the magnetotransport properties of strained 80 nm thick HgTe
      layers featuring a high mobility of MU ~ 4 * 10(5) cm(2)/V . s. By means of a top
      gate, the Fermi energy is tuned from the valence band through the Dirac-type
      surface states into the conduction band. Magnetotransport measurements allow us
      to disentangle the different contributions of conduction band electrons, holes,
      and Dirac electrons to the conductivity. The results are in line with previous
      claims that strained HgTe is a topological insulator with a bulk gap of ~ 15 meV
      and gapless surface states.

PMID- 24877959
TI  - Competition between covalent bonding and charge transfer at complex-oxide
      interfaces.
AB  - Here we study the electronic properties of cuprate-manganite interfaces. By means
      of atomic resolution electron microscopy and spectroscopy, we produce a
      subnanometer scale map of the transition metal oxidation state profile across the
      interface between the high Tc superconductor YBa2Cu3O7-delta and the colossal
      magnetoresistance compound (La,Ca)MnO3. A net transfer of electrons from
      manganite to cuprate with a peculiar nonmonotonic charge profile is observed.
      Model calculations rationalize the profile in terms of the competition between
      standard charge transfer tendencies (due to band mismatch), strong chemical
      bonding effects across the interface, and Cu substitution into the Mn lattice,
      with different characteristic length scales.

PMID- 24877960
TI  - Transport signatures of fractional fermions in Rashba nanowires.
AB  - We theoretically study transport through a semiconducting Rashba nanowire (NW) in
      the presence of uniform and spatially modulated magnetic fields. The system is
      fully gapped, and the interplay between the spin orbit interaction and the
      magnetic fields leads to fractionally charged fermion (FF) bound states of the
      Jackiw-Rebbi type at each end of the nanowire. We investigate the transport and
      noise behavior of a N/NW/N system, where the wire is contacted by two normal
      leads (N), and we look for possible signatures that could help in the
      experimental detection of such states. We find that the differential conductance
      and the shot noise exhibit a subgap structure which fully reveals the presence of
      the FF state. Alternatively, another confirmation of the presence of the FFs is
      provided by a conductance measurement in an Aharonov-Bohm setup, where the FFs
      are responsible for oscillations with double period. Our predictions can be
      tested in InSb/InAs nanowires and are within reach of the present technology. 

PMID- 24877961
TI  - Doping nature of native defects in 1T-TiSe2.
AB  - The transition-metal dichalcogenide 1T-TiSe2 is a quasi-two-dimensional layered
      material with a charge density wave (CDW) transition temperature of T(CDW) ~ 200
      K. Self-doping effects for crystals grown at different temperatures introduce
      structural defects, modify the temperature-dependent resistivity, and strongly
      perturbate the CDW phase. Here, we study the structural and doping nature of such
      native defects combining scanning tunneling microscopy or spectroscopy and ab
      initio calculations. The dominant native single atom dopants we identify in our
      single crystals are intercalated Ti atoms, Se vacancies, and Se substitutions by
      residual iodine and oxygen.

PMID- 24877962
TI  - Scaling of spin Hall angle in 3d, 4d, and 5d metals from Y3Fe5O12/metal spin
      pumping.
AB  - We have investigated spin pumping from Y3Fe5O12 thin films into Cu, Ag, Ta, W,
      Pt, and Au with varying spin-orbit coupling strengths. From measurements of
      Gilbert damping enhancement and inverse spin Hall signals spanning 3 orders of
      magnitude, we determine the spin Hall angles and interfacial spin mixing
      conductances for the six metals. The spin Hall angles largely vary as Z(4) (Z:
      atomic number), corroborating the role of spin-orbit coupling. Amongst the four
      5d metals, the variation of the spin Hall angle is dominated by the sensitivity
      of the d-orbital moment to the d-electron count, confirming theoretical
      predictions.

PMID- 24877963
TI  - Terahertz and gigahertz emission from an all-silicon nanocrystal.
AB  - Based on first-principles calculations, we predict the use of pure silicon
      nanocrystals as nano-oscillators in the giga- and terahertz region. Small- and
      large-amplitude, one-dimensional vibrations are observed. The former are
      spontaneously excited thermally at frequencies around 3 THz. Large-amplitude
      vibrations originate from oscillations between the inversion geometries of the
      nanocrystal and can be caused either classically by an external excitation or by
      quantum tunneling. The latter causes a ground-state splitting of 4.2 GHz,
      suggesting the use of the proposed nanocrystals as laser elements in a
      configuration analogous to that of the ammonia maser.

PMID- 24877964
TI  - Multiple soft-mode vibrations of lead zirconate.
AB  - Polarized Raman, IR, and time-domain THz spectroscopy of orthorhombic lead
      zirconate single crystals have yielded a comprehensive picture of temperature
      dependent quasiharmonic frequencies of its low-frequency phonon modes. It is
      argued that these modes primarily involve vibrations of Pb ions and librations of
      oxygen octahedra. Their relation to phonon modes of the parent cubic phase is
      proposed. Counts of the observed IR and Raman active modes belonging to distinct
      irreducible representations agree quite well with group-theory predictions.
      Analysis of the results yields insight into the phase transition mechanism,
      involving a soft ferroelectric branch coupled by a trilinear term to another two
      oxygen octahedra tilt modes. 

PMID- 24877965
TI  - Topological polymer dispersed liquid crystals with bulk nematic defect lines
      pinned to handlebody surfaces.
AB  - Polymer dispersed liquid crystals are a useful model system for studying the
      relationship between surface topology and defect structures. They are comprised
      of a polymer matrix with suspended spherical nematic drops and are topologically
      constrained to host defects of an elementary hedgehog charge per droplet, such as
      bulk or surface point defects or closed disclination loops. We control the genus
      of the closed surfaces confining such micrometer-sized nematic drops with
      tangential boundary conditions for molecular alignment imposed by the polymer
      matrix, allowing us to avoid defects or, on the contrary, to generate them in a
      controlled way. We show, both experimentally and through numerical modeling, that
      topological constraints in nematic microdrops can be satisfied by hosting
      topologically stable half-integer bulk defect lines anchored to opposite sides of
      handlebody surfaces. This enriches the interplay of topologies of closed surfaces
      and fields with nonpolar symmetry, yielding new unexpected configurations that
      cannot be realized in vector fields, having potential implications for
      topologically similar defects in cosmology and other fields. 

PMID- 24877966
TI  - Kovacs-like memory effect in driven granular gases.
AB  - While memory effects have been reported for dense enough disordered systems such
      as glasses, we show here by a combination of analytical and simulation techniques
      that they are also intrinsic to the dynamics of dilute granular gases. By means
      of a certain driving protocol, we prepare the gas in a state where the granular
      temperature T coincides with its long time limit. However, T does not
      subsequently remain constant but exhibits a nonmonotonic evolution before
      reaching its nonequilibrium steady value. The corresponding so-called Kovacs hump
      displays a normal behavior for weak dissipation (as observed in molecular
      systems) but is reversed under strong dissipation, where it, thus, becomes
      anomalous. 

PMID- 24877968
TI  - Anomalous dynamics of DNA hairpin folding.
AB  - By means of computer simulations of a coarse-grained DNA model we show that the
      DNA hairpin zippering dynamics is anomalous; i.e., the characteristic time tau
      scales nonlinearly with N, the hairpin length, tau ~ N(alpha) with alpha>1. This
      is in sharp contrast to the prediction of the zipper model for which tau ~ N. We
      show that the anomalous dynamics originates from an increase in the friction
      during zippering due to the tension built in the closing strands. From a simple
      polymer model we get alpha = 1+nu ~ 1.59 with nu being the Flory exponent, a
      result which is in agreement with the simulations. We discuss transition path
      times data where such effects should be detected.

PMID- 24877967
TI  - Why charged molecules move across a temperature gradient: the role of electric
      fields.
AB  - Methods to move solvated molecules are rare. Apart from electric fields, only
      thermal gradients are effective enough to move molecules inside a fluid. This
      effect is termed thermophoresis, and the underlying mechanisms are still poorly
      understood. Nevertheless, it is successfully used to quantify biomolecule binding
      in complex liquids. Here we show experiments that reveal that thermophoresis in
      water is dominated by two electric fields, both established by the salt ions of
      the solution. A local field around the molecule drives molecules along an energy
      gradient, whereas a global field moves the molecules by a combined
      thermoelectrophoresis mechanism known as the Seebeck effect. Both mechanisms
      combined predict the thermophoresis of DNA and RNA polymers for a wide range of
      experimental parameters. For example, we correctly predict a complex, nonlinear
      size transition, a salt-species-dependent offset, a maximum of thermophoresis
      over temperature, and the dependence of thermophoresis on the molecule
      concentration. 

PMID- 24877969
TI  - Phase behavior of active swimmers in depletants: molecular dynamics and integral
      equation theory.
AB  - We study the structure and phase behavior of a binary mixture where one of the
      components is self-propelling in nature. The interparticle interactions in the
      system are taken from the Asakura-Oosawa model for colloid-polymer mixtures for
      which the phase diagram is known. In the current model version, the colloid
      particles are made active using the Vicsek model for self-propelling particles.
      The resultant active system is studied by molecular dynamics methods and integral
      equation theory. Both methods produce results consistent with each other and
      demonstrate that the Vicsek model-based activity facilitates phase separation,
      thus, broadening the coexistence region. 

PMID- 24877970
TI  - Vibrationally coherent crossing and coupling of electronic states during internal
      conversion in beta-carotene.
AB  - Coupling of nuclear and electronic degrees of freedom mediates energy flow in
      molecules after optical excitation. The associated coherent dynamics in
      polyatomic systems, however, remain experimentally unexplored. Here, we combined
      transient absorption spectroscopy with electronic population control to reveal
      nuclear wave packet dynamics during the S2 -> S1 internal conversion in beta
      carotene. We show that passage through a conical intersection is vibrationally
      coherent and thereby provides direct feedback on the role of different
      vibrational coordinates in the breakdown of the Born-Oppenheimer approximation.

PMID- 24877971
TI  - Ab initio simulation of optical limiting: the case of metal-free phthalocyanine.
AB  - We present a fully ab initio, nonperturbative description of the optical limiting
      properties of a metal-free phthalocyanine by simulating the effects of a
      broadband electric field of increasing intensity. The results confirm reverse
      saturable absorption as the leading mechanism for optical limiting phenomena in
      this system and reveal that a number of dipole-forbidden excitations are
      populated by excited-state absorption at more intense external fields. The
      excellent agreement with the experimental data supports our approach as a
      powerful tool to predict optical limiting in view of applications.

PMID- 24877972
TI  - Comment on "Towards direct-gap silicon phases by the inverse band structure
      design approach".
AB  - A Comment on the Letter by H. J. Xiang, B. Huang, E. Kan, S.-H. Wei, and X. G.
      Gong, [Phys. Rev. Lett. 110, 118702 (2013).

PMID- 24877973
TI  - Xiang et al. reply.

PMID- 24877974
TI  - Preferential targeting of p39-activated Cdk5 to Rac1-induced lamellipodia.
AB  - Cdk5 is a member of the cyclin-dependent kinase (Cdk) family that plays a role in
      various neuronal activities including brain development, synaptic regulation, and
      neurodegeneration. Cdk5 requires the neuronal specific activators, p35 and p39
      for subcellular compartmentalization. However, it is not known how active Cdk5 is
      recruited to F-actin cytoskeleton, which is a Cdk5 target. Here we found p35 and
      p39 localized to F-actin rich regions of the plasma membrane and investigated the
      underlying targeting mechanism in vitro by expressing them with Rho family
      GTPases in Neuro2A cells. Both p35 and p39 accumulated at the cell peripheral
      lamellipodia and perinuclear regions, where active Rac1 is localized.
      Interestingly, p35 and p39 displayed different localization patterns as p35 was
      found more at the perinuclear region and p39 was found more in peripheral
      lamellipodia. We then confirmed this distinct localization in primary hippocampal
      neurons. We also determined that the localization of p39 to lamellipodia requires
      myristoylation and Lys clusters within the N-terminal p10 region. Additionally,
      we found that p39-Cdk5, but not p35-Cdk5 suppressed lamellipodia formation by
      reducing Rac1 activity. These results suggest that p39-Cdk5 has a dominant role
      in Rac1-dependent lamellipodial activity.

PMID- 24877975
TI  - Worldwide incidence of cervical lesions: a systematic review.
AB  - We conducted a systematic review summarizing data on incidence of high- and low
      grade lesions in women with normal baseline cervical cytology, stratified by age
      (<30 and ?30 years), and baseline human papillomavirus (HPV) infection. Incidence
      of high- and low-grade lesions in women aged ?30 years with a baseline HPV
      infection increased over follow-up time (5-127 months), although incidence
      generally remained <10%. Without baseline HPV infection, incidence of high-grade
      lesions remained low over follow-up time (<5% over 5-122 months). Incidence of
      high-grade lesions in women aged ?30 years with baseline HPV infection appeared
      similar to that in women aged <30 years. In some women aged <30 years, high-grade
      lesions can develop relatively shortly after initial HPV infection. We observed
      an increase in low-grade lesions over time in women aged ?30 years with baseline
      HPV infection, potentially indicative of an HPV infection that is potentially
      progressing to higher grade lesions.

PMID- 24877976
TI  - Ticks of the Hyalomma marginatum complex transported by migratory birds into
      Central Europe.
AB  - Hyalomma ticks are well-known vectors transmitting infectious agents, which can
      result in severe and potentially fatal diseases in humans. Migratory birds may
      carry infected ticks over long distances. Here, we report on records of ticks of
      the H. marginatum complex in birds from Central Europe during the spring
      migration in 2008-2012. A total of 1172 birds belonging to 32 species, 16
      families, and 3 orders was examined for ticks. Sixteen individuals of 6 passerine
      species were found to transport 30 ticks, identified as individuals belonging to
      the H. marginatum species complex (consisting of H. isaaci, H. marginatum sensu
      stricto, H. rufipes, H. turanicum, and H. glabrum) during 5 spring seasons.
      Infested bird species included the great reed warbler Acrocephalus arundinaceus,
      the Eurasian reed warbler A. scirpaceus, the marsh warbler A. palustris, the
      sedge warbler A. schoenobaenus, Savi's warbler Locustella luscinioides, and the
      common nightingale Luscinia megarhynchos. All of these Central European breeders
      are migratory species wintering in Africa. To our knowledge, this is the first
      study to record ticks of the H. marginatum complex on the great reed warbler and
      Savi's warbler. 

PMID- 24877977
TI  - Use of Percoll gradients to purify Anaplasma marginale (Rickettsiales:
      Anaplasmataceae) from tick cell cultures.
AB  - Anaplasma marginale (Rickettsiales: Anaplasmataceae) is an obligate intracellular
      bacterium that multiplies exclusively within membrane-bound vacuoles in the
      cytoplasm of host cells. A number of A. marginale isolates can be propagated in
      the Ixodes scapularis IDE8 tick cell line, which provides a reliable source of
      antigens for a wide variety of studies. However, because of its intracellular
      nature, separation of bacteria from host cell materials remains an important
      constraint for researchers. In the present study, we evaluated the use of Percoll
      gradients for purification of two Brazilian strains of A. marginale grown in IDE8
      tick cells. The purified A. marginale monitored in Giemsa-stained smears
      contained only minimal amounts of IDE8 cell stroma. The total protein yields were
      1.2mg and 1.7mg, while the DNA titers quantified with real-time PCR were
      6.4*10(9) for UFMG1 and 4.87*10(9) for UFMG2 copies in the purified material,
      respectively. Additionally, we confirmed the viability of purified bacteria by
      infecting tick cells after being freshly purified and after retrieval from long
      term storage. Importantly, the viability of the organisms is preserved after use
      of this separation method, and therefore the purified organisms can be used in
      enzymatic assays and other research approaches where live organisms would be
      preferred. 

PMID- 24877978
TI  - Evaluation of the stability of a mixture of volatile organic compounds on
      sorbents for the determination of emissions from indoor materials and products
      using thermal desorption/gas chromatography/mass spectrometry.
AB  - The standard method for the determination of volatile organic compounds (VOCs) in
      indoor and test chamber air (ISO 16000-6:2011) specifies sampling onto the
      sorbent Tenax TA followed by analysis using thermal desorption/gas
      chromatography/mass spectrometry (TD/GC/MS). The informative Annex D to the
      standard suggests the use of multi-sorbent samplers to extend the volatility
      range of compounds which can be determined. The aim of this study was to
      investigate the storage performance of Tenax TA and two multi-sorbent tubes
      loaded with a mixture of nine VOCs of relevance for material emissions testing.
      The sorbent combinations tested were quartz wool/Tenax TA/CarbographTM 5TD and
      quartz wool/Tenax TA/CarbopackTM X. A range of loading levels, loading conditions
      (humidities and air volume), storage times (1-4 weeks) and storage conditions
      (refrigerated and ambient) were investigated. Longer term storage trials (up to 1
      year) were conducted with Tenax TA tubes to evaluate the stability of tubes used
      for proficiency testing (PT) of material emissions analyses. The storage
      performance of the multi-sorbent tubes tested was found to be equal to that for
      Tenax TA, with recoveries after 4 weeks storage of within about 10% of the
      amounts loaded. No consistent differences in recoveries were found for the
      different loading or storage conditions. The longer term storage trials also
      showed good recovery for these compounds, although two other compounds, hexanal
      and BHT, were found to be unstable when stored on Tenax TA. The results of this
      study provide confidence in the stability of nine analytes for up to 4 weeks on
      two multi-sorbent tubes for material emissions testing and the same compounds
      loaded on Tenax TA sorbent for a recently introduced PT scheme for material
      emissions testing. 

PMID- 24877979
TI  - Determination of pore size distributions in capillary-channeled polymer fiber
      stationary phases by inverse size-exclusion chromatography and implications for
      fast protein separations.
AB  - Capillary-channeled polymer (C-CP) fibers have been utilized as liquid
      chromatography stationary phases, primarily for biomacromolecule separations on
      the analytical and preparative scales. The collinear packing of the eight
      channeled C-CP fibers provides for very efficient flow, allowing operation at
      high linear velocity (u>100mm s(-1)) and low backpressure (<2000psi) in
      analytical-scale separations. To take advantage of these fluid transport
      properties, there must not be mass transfer limitations as would be imposed by
      having an appreciably porous phase, wherein solute diffusion limits the overall
      mass transport rates. To better understand the physical nano-/micro- structure of
      C-CP fibers, inverse size exclusion chromatography (iSEC) has been employed to
      determine the pore size distribution (PSD) within C-CP fibers. A diversity of
      test species (from metal ions to large proteins) was used as probes under non
      retaining conditions to obtain a response curve reflecting the apparent partition
      coefficient (Kd) versus hydrodynamic radii (rm). A mean pore radius (rp) of 4.2nm
      with standard deviation (sp) of +/-1.1nm was calculated by fitting the Kd versus
      rm data to model equations with a Gaussian pore size distribution, and a pore
      radius of 4.0+/-0.1nm was calculated based on a log-normal distribution. The
      derived mean pore radius is much smaller than traditional support materials, with
      the standard deviation showing a relatively uniform pore distribution. van
      Deemter plots were analyzed to provide practical confirmation of the structural
      implications. Large molecules (e.g., proteins) that are fully excluded from pores
      have no significant C-terms in the van Deemter plots whereas small molecules that
      can access the pore volumes display appreciable C-terms, as expected. Fitting of
      retention data to the Knox equation suggests that the columns operate with a
      characteristic particle diameter (dp) of ~53MUm. 

PMID- 24877980
TI  - Planar solid phase extraction clean-up and microliter-flow injection analysis
      time-of-flight mass spectrometry for multi-residue screening of pesticides in
      food.
AB  - For multi-residue analysis of pesticides in food, a sufficient clean-up is
      essential for avoiding matrix effects in liquid and gas chromatography (LC and
      GC) analysis coupled to mass spectrometry (MS). In the last two years, high
      throughput planar solid phase extraction (HTpSPE) was established as a new clean
      up concept for pesticide residue analysis in fruits and vegetables (C. Oellig, W.
      Schwack, 2011) and tea (C. Oellig, W. Schwack, 2012). HTpSPE results in matrix
      free extracts almost free of interferences and matrix effects. In this study, a
      time-of-flight mass spectrometer (TOFMS) was applied to directly analyze HTpSPE
      extracts for pesticide residues. This HTpSPE-microliter-flow injection analysis
      (MUL-FIA)-TOFMS approach detects all pesticides at once in a single mass
      spectrum, without a liquid chromatographic separation step. Complete sample
      information was obtained after the injection of the cleaned extract within a
      single peak. Recovery studies for seven representative pesticides in four
      different matrices (apples, red grapes, cucumbers, tomatoes) provided mean
      recoveries of 86-116% with relative standard deviations of 1.3-10% (n=5) using
      the mass signal intensities under the entire sample peak. Comparing the mass
      spectra of sample peaks from spiked extracts and solvent standards indicated the
      efficiency of HTpSPE clean-up. A pesticide database search detected all spiked
      pesticides with a low incidence of false-positives. HTpSPE of one sample required
      a few minutes, and numerous samples could be cleaned in parallel at minimal cost
      with low sample and solvent consumption. The MUL-FIA-TOFMS screening then needed
      an additional 6min per sample. The novel screening approach was successfully
      applied to QuEChERS extracts of several real samples, and the pesticides
      identified by HTpSPE-MUL-FIA-TOFMS were identical to the pesticides detected by
      common target LC-MS/MS analyses. The high degree of concordantly identified
      pesticides by the new developed HTpSPE-MUL-FIA-TOFMS approach and target LC-MS/MS
      demonstrates the applicability as a routine screening method. 

PMID- 24877981
TI  - Double water compatible molecularly imprinted polymers applied as solid-phase
      extraction sorbent for selective preconcentration and determination of triazines
      in complicated water samples.
AB  - In the present work, double water compatible molecularly imprinted polymers (DWC
      MIPs) with water compatible core and hydrophilic polymer brushes were prepared by
      reversible addition-fragmentation chain transfer precipitate polymerization
      (RAFTPP) and applied as solid-phase extraction (SPE) sorbent for selective
      preconcentration and specific recognition of triazines in water samples. The DWC
      MIPs employed as SPE sorbent presented much higher extraction efficiency for four
      triazines in aqueous media based on the double water compatible property. The
      validated method was also successfully applied to tap water and river water
      sample analysis, and satisfactory recoveries were attained, such as 69.2-95.4%
      with the precision of 1.59-3.94% for four triazines at 100MUgL(-1). The DWC-MIPs
      SPE proves to be a highly effective cleanup and enrichment method for
      simultaneous separation and sensitive determination of triazines in complicated
      water samples. 

PMID- 24877982
TI  - Diffusion-weighted MR imaging in thymic epithelial tumors: correlation with World
      Health Organization classification and clinical staging.
AB  - PURPOSE: To assess thymic epithelial tumors with diffusion-weighted magnetic
      resonance (MR) imaging. MATERIALS AND METHODS: Informed consent from patients and
      institutional review board approval were obtained. Prospective study was
      conducted on 30 consecutive patients (21 men and nine women; age range, 35-71
      years) with thymic epithelial tumors. They underwent true fast imaging with
      steady-state precession and single-shot echo-planar diffusion-weighted MR imaging
      of the mediastinum with b values of 0, 400, and 800 sec/mm(2). Apparent diffusion
      coefficient (ADC) of the thymic epithelial tumors was calculated by the same
      observer at two settings and was correlated with World Health Organization
      classification and clinical staging. RESULTS: There was significant difference in
      longest diameter (P = .001) and necrotic part of the tumor (P = .014) between low
      risk thymoma, high-risk thymoma, and thymic carcinoma. Mean ADC value of both
      readings of thymic epithelial tumors (n = 30) was 1.24 * 10(-3) mm(2)/sec and
      1.22 * 10(-3) mm(2)/sec, with good intraobserver agreement (kappa = 0.732). There
      was significant difference in both readings (P = .01 and .20) of low-risk thymoma
      (1.30 * 10(-3) mm(2)/sec and 1.29 * 10(-3) mm(2)/sec), high-risk thymoma (1.16 *
      10(-3) mm(2)/sec and 1.14 * 10(-3) mm(2)/sec), and thymic carcinoma (1.18 * 10(
      3) mm(2)/sec and 1.06 * 10(-3) mm(2)/sec). Cutoff ADC values of both readings
      used to differentiate low-risk thymoma from high-risk thymoma and thymic
      carcinoma were 1.25 and 1.22 * 10(-3) mm(2)/sec with area under the curve of
      0.804 and 0.851, respectively. There was significant difference in both readings
      of ADC value of early (stage I, II) and advanced stages (stage III, IV) of thymic
      epithelial tumors (P = .006 and .005, respectively). CONCLUSION: ADC value is a
      noninvasive, reliable, and reproducible imaging parameter that may help to assess
      and characterize thymic epithelial tumors.

PMID- 24877983
TI  - Simultaneous whole-body PET/MR imaging in comparison to PET/CT in pediatric
      oncology: initial results.
AB  - PURPOSE: To compare positron emission tomography (PET)/magnetic resonance (MR)
      imaging and PET/computed tomography (CT) for lesion detection and interpretation,
      quantification of fluorine 18 ((18)F) fluorodeoxyglucose (FDG) uptake, and
      accuracy of MR-based PET attenuation correction in pediatric patients with solid
      tumors. Materials and Methods This prospective study had local ethics committee
      and German Federal Institute for Drugs and Medical Devices approval. Written
      informed consent was obtained from all patients and legal guardians. Twenty whole
      body (18)F-FDG PET/CT and (18)F-FDG PET/MR examinations were performed in 18
      pediatric patients (median age, 14 years; range, 11-17 years). (18)F-FDG PET/CT
      and (18)F-FDG PET/MR data were acquired sequentially on the same day for all
      patients. PET standardized uptake values (SUVs) were quantified with volume of
      interest measurements in lesions and healthy tissues. MR-based PET attenuation
      correction was compared with CT-derived attenuation maps (u-maps). Lesion
      detection was assessed with separate reading of PET/CT and PET/MR data. Estimates
      of radiation dose were derived from the applied doses of (18)F-FDG and CT
      protocol parameters. Descriptive statistical analyses were performed to report
      correlation coefficients and relative deviations for comparison of SUVs, rates of
      lesion detection, and percentage reductions in radiation dose. RESULTS: PET SUVs
      showed strong correlations between PET of PET/CT (PETCT) and PET of PET/MR
      (PETMR) (r > 0.85 for most tissues). Apart from drawbacks of MR-based PET
      attenuation correction in osseous structures and lungs, similar SUVs were found
      on PET images corrected with CT-based u-maps (13.1% deviation of SUVs for bone
      marrow and <5% deviation for other tissues). Lesion detection rate with PET/MR
      imaging was equivalent to that with PET/CT (61 areas of focal uptake on PETMR
      images vs 62 areas on PETCT images). Advantages of PET/MR were observed
      especially in soft-tissue regions. Furthermore, PET/MR offered significant dose
      reduction (73%) compared with PET/CT. CONCLUSION: Pediatric oncologic PET/MR is
      technically feasible, showing satisfactory performance for PET quantification
      with SUVs similar to those of PET/CT. Compared with PET/CT, PET/MR demonstrates
      equivalent lesion detection rates while offering markedly reduced radiation
      exposure. Thus, PET/MR is a promising modality for the clinical work-up of
      pediatric malignancies. Online supplemental material is available for this
      article.

PMID- 24877984
TI  - Closing in on the K edge: coronary CT angiography at 100, 80, and 70 kV-initial
      comparison of a second- versus a third-generation dual-source CT system.
AB  - PURPOSE: To prospectively evaluate radiation and contrast medium requirements for
      performing high-pitch coronary computed tomographic (CT) angiography at 70 kV
      using a third-generation dual-source CT system in comparison to a second
      generation dual-source CT system. MATERIALS AND METHODS: All patients gave
      informed consent for this institutional review board-approved study. Forty-five
      patients (median age, 52 years; 27 men) were imaged in high-pitch mode with a
      third-generation dual-source CT system at 70 kV (n = 15) or with a second
      generation dual-source CT system at 80 or 100 kV (n = 15 for each). Tube voltage
      was based on body mass index: 80 or 70 kV for less than 26 kg/m(2) versus 100 kV
      for 26-30 kg/m(2). For the 80- and 100-kV protocols, 80 mL of contrast material
      was injected, versus 45 mL for the 70-kV protocol. Data were reconstructed by
      using a second-generation iterative reconstruction algorithm for second
      generation dual-source CT and a recently introduced third-generation iterative
      reconstruction algorithm for third-generation dual-source CT. Objective image
      quality was measured for various regions of interest, and subjective image
      quality was evaluated with a five-point Likert scale. RESULTS: The signal-to
      noise ratio of the coronary CT angiography studies acquired with 70 kV was
      significantly higher (70 kV: 14.3-17.6 vs 80 kV: 7.1-12.9 vs 100 kV: 9.8-12.9; P
      < .0497) than those acquired with the other two protocols for all coronary
      arteries. Qualitative image quality analyses revealed no significant differences
      between the three CT angiography protocols (median score, 5; P > .05). The mean
      effective dose was 75% and 108% higher (0.92 mSv +/- 0.3 [standard deviation] and
      0.78 mSv +/- 0.2 vs 0.44 mSv +/- 0.1; P < .0001), respectively, for the 80- and
      100-kV CT angiography protocols than for the 70-kV CT angiography protocol.
      CONCLUSION: In nonobese patients, third-generation high-pitch coronary dual
      source CT angiography at 70 kV results in robust image quality for studying the
      coronary arteries, at significantly reduced radiation dose (0.44 mSv) and
      contrast medium volume (45 mL), thus enabling substantial radiation dose and
      contrast medium savings as compared with second-generation dual-source CT.

PMID- 24877986
TI  - Systemic therapy in neurofibromatosis type 2.
AB  - The systemic treatment of patients with neurofibromatosis type 2 associated
      tumours is challenging, as these patients often have prolonged survival but with
      the inevitable propensity for their disease to cause symptoms, and no effective
      therapies other than local treatments such as surgery. Understanding the
      molecular mechanisms driving NF-2 pathogenesis holds promise for the potential
      use of targeted therapy. Initial studies of agents such as bevacizumab
      (angiogenesis inhibitor) and lapatinib (epidermal growth factor and ErbB2
      inhibitor) have indicated benefit for selected patients. As the biology of NF-2
      is dependent on multiple interlinked downstream signalling pathways, targeting
      multiple pathways may be more effective than single agents. Phase zero trials,
      adaptive phase II or small multi-arm trials, are likely the way forward in this
      rare disease. Ideally, well-tolerated targeted therapy would appear to be the
      most promising approach for patients with NF-2, given the natural history of this
      disease.

PMID- 24877985
TI  - The independent contribution of diabetic foot ulcer on lower extremity amputation
      and mortality risk.
AB  - AIMS: To estimate 3-year risk for diabetic foot ulcer (DFU), lower extremity
      amputation (LEA) and death; determine predictive variables and assess derived
      models accuracy. MATERIAL AND METHODS: Retrospective cohort study including all
      subjects with diabetes enrolled in our diabetic foot outpatient clinic from
      beginning 2002 until middle 2010. Data were collected from clinical records.
      RESULTS: 644 subjects with mean age of 65.1 (+/-11.2) and diabetes duration of
      16.1 (+/-10.8) years. Cumulative incidence was 26.6% for DFU, 5.8% for LEA and
      14.0% for death. In multivariate analysis, physical impairment, peripheral
      arterial disease complication history, complication count and previous DFU were
      associated with DFU; complication count, foot pulses and previous DFU with LEA
      and age, complication count and previous DFU with death. Predictive models' areas
      under the ROC curves ranged from 0.80 to 0.83. A simplified model including
      previous DFU and complication count presented high accuracy. Previous DFU was
      associated with all outcomes, even when adjusted for complication count, in
      addition to more complex models. CONCLUSIONS: DFU seems more than a marker of
      complication status, having independent impact on LEA and mortality risk.
      Proposed models may be applicable in healthcare settings to identify patients at
      higher risk of DFU, LEA and death.

PMID- 24877987
TI  - Impact of neoadjuvant single or dual HER2 inhibition and chemotherapy backbone
      upon pathological complete response in operable and locally advanced breast
      cancer: Sensitivity analysis of randomized trials.
AB  - The role of the dual HER2 inhibition, and the best chemotherapy backbone for
      neoadjuvant chemotherapy still represent an issue for clinical practice. A
      literature-based meta-analysis exploring single versus dual HER2 inhibition in
      terms of pathological complete response (pCR, breast plus axilla) rate and
      testing the interaction according to the chemotherapy (anthracyclines-taxanes or
      taxanes) was conducted. In addition, an event-based pooled analysis by extracting
      activity and safety events and deriving 95% confidence intervals (CI) was
      accomplished. Fourteen trials (4149 patients) were identified, with 6 trials
      (1820 patients) included in the meta-analysis and 31 arms (14 trials, 3580
      patients) in the event-based pooled analysis. The dual HER2 inhibition
      significantly improves pCR rate, in the range of 16-19%, regardless of the
      chemotherapy backbone (relative risk 1.37, 95% CI 1.23-1.53, p<0.0001); pCR was
      significantly higher in the hormonal receptor negative population, regardless of
      the HER2 inhibition and type of chemotherapy. pCR and the rate of breast
      conserving surgery was higher when anthracyclines were added to taxanes,
      regardless of the HER2 inhibition. Severe neutropenia was higher with the
      addition of anthracyclines to taxanes, with an absolute difference of 19.7%,
      despite no differences in febrile neutropenia. While no significant differences
      according to the HER2 inhibition were found in terms of cardiotoxicity, a
      slightly difference for grade 3-4 (1.2%) against the addition of anthracyclines
      was calculated. The dual HER2 inhibition for the neoadjuvant treatment of HER2
      positive breast cancer significantly increases pCR; the combination of
      anthracyclines, taxanes and anti-Her2 agents should be currently considered the
      standard of care.

PMID- 24877988
TI  - Comparative study of primary intention lacrimal probing with and without nasal
      endoscopy.
AB  - OBJECTIVE: Our objective was to compare the results of probing with and without
      endoscopy in cases of congenital nasolacrimal duct obstruction without prior
      probing. METHODS: This was a retrospective analysis on 2 non-randomized cohorts,
      36 simple soundings (group 1) and 36 soundings with endoscope (group 2), between
      January 2011 and January 2013. Both groups were similar in age and had no
      previous surgery. The age of the patients studied ranged between 8 and 27 months
      in the first group and between 7 and 30 months in the second group. RESULTS: The
      procedure was successful in 50% of the conventional probing group and in 97.22%
      in the endoscopy probing group. In this group 16.67% of patients with tight
      inferior turbinate and 11.11% of those where the probe passed into the submucosal
      space were diagnosed and corrected intraoperatively. Some anomaly was observed in
      30.56% of patients undergoing endoscopy. CONCLUSION: Although nasal endoscopy is
      classically reserved for unsuccessful probing, its use in primary intention
      increases the success rate of the procedure. In our study, 97.22% of eyes had
      complete resolution of symptoms, avoiding a second surgery and the use of more
      expensive materials and techniques. Nasal endoscopy helps intraoperative
      visualisation, understanding and management of congenital nasolacrimal duct
      obstruction and is the only method that confirms the correct anatomic position of
      the catheterisation in real time.

PMID- 24877989
TI  - Diet and esophageal cancer risk in the Eastern Cape Province of South Africa.
AB  - A multicenter hospital-based case-control study comprising 670 incident cases of
      esophageal cancer (EC) and 1188 controls, frequency-matched for age and sex, was
      conducted to evaluate the role of diet on EC development in the Eastern Cape
      Province, South Africa. A locally relevant lifestyle and dietary questionnaire
      was used. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were
      computed using unconditional multivariable logistic regression. Individually,
      maize or sorghum consumption vs. never or rare consumption were not associated
      with EC (P > 0.1). Males and females consuming green leafy vegetables 5-7 days/wk
      had 38% (P = 0.04) and 50% (P = 0.007) reduced odds of developing EC,
      respectively, compared with consumption <=1 day/wk. A similar reduction in odds
      was observed with fruit consumption. Principal component factor analysis revealed
      3 distinct dietary patterns. In females, high vs. low consumption of Pattern 1
      (sorghum, green leafy vegetables, green legumes, fruits, meat) was inversely
      associated with EC development (OR = 0.54; 95% CI: 0.34-0.89), whereas for
      Pattern 2 (maize, wild greens-imifino, dry beans) the odds were elevated (OR =
      1.67; 95% CI: 1.04-2.67). Compared with low adherence, high adherence to Pattern
      3 (wheat-based products) reduced the odds by 35% for both sexes. This study
      provides further evidence on the role of diet in minimizing EC risk in this
      population.

PMID- 24877990
TI  - Polyplex formation between PEGylated linear cationic block copolymers and DNA:
      equilibrium and kinetic studies.
AB  - The basic requirement for understanding the nonviral gene delivery pathway is a
      thorough biophysical characterization of DNA polyplexes. In this work, we have
      studied the interactions between calf-thymus DNA (ctDNA)and a new series of
      linear cationic block copolymers (BCPs). The BCPs were synthesized via controlled
      radical polymerization using [3-(methacryloylamino)propyl] -trimethylammonium
      chloride (MAPTAC) and poly(ethyleneglycol) methyl ether (PEGMe) as comonomers. UV
      visible spectroscopy, ethidium bromide dye exclusion, and gel electrophoresis
      study revealed that these cationic BCPs were capable of efficiently binding with
      DNA. Steady-state fluorescence, UV melting, gel electrophoresis, and circular
      dichroism results suggested increased binding for BCPs containing higher PEG.
      Hydrophobic interactions between the PEG and the DNA base pairs became
      significant at close proximity of the two macromolecules, thereby influencing the
      binding trend. DLS studies showed a decrease in the size of DNA molecules at
      lower charge ratio (the ratio of "+" charge of the polymer to "-" charge of DNA)
      due to compaction, whereas the size increased at higher charge ratio due to
      aggregation among the polyplexes. Additionally, we have conducted kinetic studies
      of the binding process using the stop-flow fluorescence method. All the results
      of BCP-DNA binding studies suggested a two-step reaction mechanism--a rapid
      electrostatic binding between the cationic blocks and DNA, followed by a
      conformational change of the polyplexes in the subsequent step that led to DNA
      condensation. The relative rate constant(k'(1)) of the first step was much higher
      compared to that of the second step (k'(2)), and both were found to increase with
      an increase in BCP concentration. The charge ratios as well as the PEG content in
      the BCPs had a marked effect on the kinetics of the DNA-BCP polyplex formation.
      Introduction of a desired PEG chain length in the synthesized cationic blocks
      renders them potentially useful as nonviral gene delivery agents.

PMID- 24877991
TI  - Isolable 1,1-disubstituted silole dianion: a homogeneous two-electron-transfer
      reducing reagent.
AB  - The 1,1-disubstituted silole dianion 2 has been isolated and characterized by
      single-crystal X-ray analysis for the first time. 2 can be used as a two-electron
      transfer reducing reagent for the reduction of organic compounds and inorganic
      salts with regeneration of the corresponding neutral silole in nearly
      quantitative yields, indicating that it is an excellent reducing reagent.
      Reduction of (Mes)2SiCl2 with 2 selectively yielded the cyclotrisilane (Mes2Si)3
      in high yield, which has not been isolated in pure form with the existing
      methods. 

PMID- 24877992
TI  - Rotaxane-based molecular muscles.
AB  - CONSPECTUS: More than two decades of investigating the chemistry of bistable
      mechanically interlocked molecules (MIMs), such as rotaxanes and catenanes, has
      led to the advent of numerous molecular switches that express controlled
      translational or circumrotational movement on the nanoscale. Directed motion at
      this scale is an essential feature of many biomolecular assemblies known as
      molecular machines, which carry out essential life-sustaining functions of the
      cell. It follows that the use of bistable MIMs as artificial molecular machines
      (AMMs) has been long anticipated. This objective is rarely achieved, however,
      because of challenges associated with coupling the directed motions of mechanical
      switches with other systems on which they can perform work. A natural source of
      inspiration for designing AMMs is muscle tissue, since it is a material that
      relies on the hierarchical organization of molecular machines (myosin) and
      filaments (actin) to produce the force and motion that underpin locomotion,
      circulation, digestion, and many other essential life processes in humans and
      other animals. Muscle is characterized at both microscopic and macroscopic length
      scales by its ability to generate forces that vary the distance between two
      points at the expense of chemical energy. Artificial muscles that mimic this
      ability are highly sought for applications involving the transduction of
      mechanical energy. Rotaxane-based molecular switches are excellent candidates for
      artificial muscles because their architectures intrinsically possess movable
      filamentous molecular components. In this Account, we describe (i) the different
      types of rotaxane "molecular muscle" architectures that express contractile and
      extensile motion, (ii) the molecular recognition motifs and corresponding stimuli
      that have been used to actuate them, and (iii) the progress made on integrating
      and scaling up these motions for potential applications. We identify three types
      of rotaxane muscles, namely, "daisy chain", "press", and "cage" rotaxanes, and
      discuss their mechanical actuation driven by ions, pH, light, solvents, and redox
      stimuli. Different applications of these rotaxane-based molecular muscles are
      possible at various length scales. On a molecular level, they have been harnessed
      to create adjustable receptors and to control electronic communication between
      chemical species. On the mesoscale, they have been incorporated into artificial
      muscle materials that amplify their concerted motions and forces, making future
      applications at macroscopic length scales look feasible. We emphasize how
      rotaxanes constitute a remarkably versatile platform for directing force and
      motion, owing to the wide range of stimuli that can be used to actuate them and
      their diverse modes of mechanical switching as dictated by the stereochemistry of
      their mechanical bonds, that is, their mechanostereochemistry. We hope that this
      Account will serve as an exposition that sets the stage for new applications and
      materials that exploit the capabilities of rotaxanes to transduce mechanical
      energy and help in paving the path going forward to genuine AMMs.

PMID- 24877993
TI  - Predictors of decreased physical activity level over time among adults: a
      longitudinal study.
AB  - BACKGROUND: Leisure-time physical activity (LTPA) plays a key role in chronic
      disease prevention and health promotion. The impact of life-changing events on
      LTPA among adults is unknown. PURPOSE: To examine the association between life
      changing events and decreased LTPA levels. METHODS: Eight cycles of Canadian
      National Population Health Survey data were used for this study. A total of
      12,901 respondents aged >=18 years in 1994-1995 completed biannual follow-ups
      until 2008-2009. The association between life-changing events and decreased LTPA
      in any 2-year period was assessed with adjustment of potential confounding
      factors. Data were analyzed in 2012. RESULTS: From 1994-1995 to 2008-2009, nine
      of ten people changed their LTPA levels. Within each 2-year period, individuals
      were more likely to decrease their LTPA levels if they married within the 2-year
      period (men); became or remained overweight/obese (women); remained a regular
      smoker (men); became or remained unhealthy (men and women); developed or
      continued to have body pain (women); and acquired social support or remained
      without support (men). CONCLUSIONS: Most people change their LTPA levels or
      patterns, which are significantly influenced by life-changing events. An improved
      understanding of factors that influence LTPA may help better target those at high
      risk.

PMID- 24877994
TI  - Significant absences: the luxury of "being less critical".

PMID- 24877995
TI  - Ranolazine inhibition of hERG potassium channels: drug-pore interactions and
      reduced potency against inactivation mutants.
AB  - The antianginal drug ranolazine, which combines inhibitory actions on rapid and
      sustained sodium currents with inhibition of the hERG/IKr potassium channel,
      shows promise as an antiarrhythmic agent. This study investigated the structural
      basis of hERG block by ranolazine, with lidocaine used as a low potency,
      structurally similar comparator. Recordings of hERG current (IhERG) were made
      from cell lines expressing wild-type (WT) or mutant hERG channels. Docking
      simulations were performed using homology models built on MthK and KvAP
      templates. In conventional voltage clamp, ranolazine inhibited IhERG with an IC50
      of 8.03MUM; peak IhERG during ventricular action potential clamp was inhibited
      ~62% at 10MUM. The IC50 values for ranolazine inhibition of the S620T
      inactivation deficient and N588K attenuated inactivation mutants were
      respectively ~73-fold and ~15-fold that for WT IhERG. Mutations near the bottom
      of the selectivity filter (V625A, S624A, T623A) exhibited IC50s between ~8 and 19
      fold that for WT IhERG, whilst the Y652A and F656A S6 mutations had IC50s ~22
      fold and 53-fold WT controls. Low potency lidocaine was comparatively insensitive
      to both pore helix and S6 mutations, but was sensitive to direction of K(+) flux
      and particularly to loss of inactivation, with an IC50 for S620T-hERG ~49-fold
      that for WT IhERG. Docking simulations indicated that the larger size of
      ranolazine gives it potential for a greater range of interactions with hERG pore
      side chains compared to lidocaine, in particular enabling interaction of its two
      aromatic groups with side chains of both Y652 and F656. The N588K mutation is
      responsible for the SQT1 variant of short QT syndrome and our data suggest that
      ranolazine is unlikely to be effective against IKr/hERG in SQT1 patients. 

PMID- 24877998
TI  - Stumbles on the path to dengue control.

PMID- 24877997
TI  - Efficacy and safety of celgosivir in patients with dengue fever (CELADEN): a
      phase 1b, randomised, double-blind, placebo-controlled, proof-of-concept trial.
AB  - BACKGROUND: Dengue infection is the most common mosquito-borne viral disease
      worldwide, but no suitable antiviral drugs are available. We tested the alpha
      glucosidase inhibitor celgosivir as a treatment for acute dengue fever. METHODS:
      To establish eligibility for inclusion in a phase 1b, randomised, double-blind,
      placebo-controlled, proof-of-concept trial, individuals aged 21-65 years who had
      had a fever (>=38 degrees C) for less than 48 h, met at least two criteria
      indicating probable dengue infection, and had a positive result on a dengue point
      of-care test kit or PCR assay were referred for screening at a centre in
      Singapore between July 30, 2012, and March 4, 2013. Using a web-based system, we
      randomly assigned patients who met full inclusion criteria after screening (1:1;
      random permuted block length four) to celgosivir (initial 400 mg loading dose
      within 6 h of randomisation, followed by 200 mg every 12 h for a total of nine
      doses) or matched placebo. Patients and the entire study team were masked to
      group assignment. The primary endpoints were mean virological log reduction (VLR)
      from baseline for days 2, 3, and 4, and area under the fever curve (AUC) for a
      temperature above 37 degrees C from 0 h to 96 h. Efficacy analyses were by
      intention to treat. This study is registered with ClinicalTrials.gov, number
      NCT01619969. FINDINGS: We screened 69 patients and randomly assigned 50 (24 to
      celgosivir, 26 to placebo). Mean VLR was greater in the celgosivir group (-1.86,
      SD 1.07) than in the placebo group (-1.64, 0.75), but the difference was non
      significant (-0.22, 90% CI -0.65 to 0.22; one-sided p=0.203). The mean AUC was
      also higher in the celgosivir group (54.92, SD 31.04) than in the placebo group
      (40.72, 18.69), but again the difference was non-significant (14.20, 90% CI 2.16
      26.25; one-sided p=0.973). We noted similar incidences of adverse events between
      groups. INTERPRETATION: Although generally safe and well tolerated, celgosivir
      does not seem to reduce viral load or fever burden in patients with dengue.
      FUNDING: STOP Dengue Translational Clinical Research.

PMID- 24877999
TI  - Computational design of allosteric ribozymes as molecular biosensors.
AB  - Nucleic acids have proven to be a very suitable medium for engineering various
      nanostructures and devices. While synthetic DNAs are commonly used for self
      assembly of nanostructures and devices in vitro, functional RNAs, such as
      ribozymes, are employed both in vitro and in vivo. Allosteric ribozymes have
      applications in molecular computing, biosensoring, high-throughput screening
      arrays, exogenous control of gene expression, and others. They switch on and off
      their catalytic function as a result of a conformational change induced by ligand
      binding. Designer ribozymes are engineered to respond to different effectors by
      in vitro selection, rational and computational design methods. Here, I present
      diverse computational methods for designing allosteric ribozymes with various
      logic functions that sense oligonucleotides or small molecules. These methods
      yield the desired ribozyme sequences within minutes in contrast to the in vitro
      selection methods, which require weeks. Methods for synthesis and biochemical
      testing of ribozymes are also discussed. 

PMID- 24877996
TI  - Infection-induced inflammation and cerebral injury in preterm infants.
AB  - Preterm birth and infectious diseases are the most common causes of neonatal and
      early childhood deaths worldwide. The rates of preterm birth have increased over
      recent decades and account for 11% of all births worldwide. Preterm infants are
      at significant risk of severe infection in early life and throughout childhood.
      Bacteraemia, inflammation, or both during the neonatal period in preterm infants
      is associated with adverse outcomes, including death, chronic lung disease, and
      neurodevelopmental impairment. Recent studies suggest that bacteraemia could
      trigger cerebral injury even without penetration of viable bacteria into the CNS.
      Here we review available evidence that supports the concept of a strong
      association between bacteraemia, inflammation, and cerebral injury in preterm
      infants, with an emphasis on the underlying biological mechanisms, clinical
      correlates, and translational opportunities. 

PMID- 24878000
TI  - SOX11 as a minimal residual disease marker for Mantle cell lymphoma.
AB  - Recent studies have identified SOX11 as a novel diagnostic marker for mantle cell
      lymphoma (MCL). We quantified SOX11 by a truly mRNA specific qPCR assay in
      longitudinal peripheral blood samples from 20 patients and evidenced a close
      relationship of SOX11 expression and clinical status of the patients. In eight
      patient courses we validated the expression of SOX11 using t(11;14) and
      demonstrated positive correlation of SOX11 and t(11;14) levels. To the best of
      our knowledge this is the first report stating that quantification of SOX11 can
      be used as an minimal residual disease marker equal to the key translocation
      t(11;14) in MCL. 

PMID- 24878001
TI  - Comparison of promoter DNA methylation and expression levels of genes encoding
      CCAAT/enhancer binding proteins in AML patients.
AB  - CCAAT/enhancer binding proteins (CEBPs) are transcription factors regulating
      myeloid differentiation. Disturbances of their expression may contribute to
      leukemogenesis. In this study we compared promoter methylation and expression
      levels of selected CEBP genes in a group of 78 AML patients, normal bone marrow
      and hematopoietic precursor cells. CEBPA, CEBPD and CEBPE promoter methylation
      levels were elevated in 37%, 35.5% and 56.7% of patients. No CEBPZ(DDIT3)
      methylation was observed. An inverse relationship between CEBPA and CEBPD DNA
      methylation and expression levels was observed. AML cytogenetic risk groups and
      patients with particular translocation are characterized by distinct
      methylation/expression profile of CEBPs encoding genes.

PMID- 24878003
TI  - S/G-1: an ab initio force-field blending frozen Hermite Gaussian densities and
      distributed multipoles. Proof of concept and first applications to metal cations.
AB  - We demonstrate as a proof of principle the capabilities of a novel hybrid MM'/MM
      polarizable force field to integrate short-range quantum effects in molecular
      mechanics (MM) through the use of Gaussian electrostatics. This lead to a further
      gain in accuracy in the representation of the first coordination shell of metal
      ions. It uses advanced electrostatics and couples two point dipole polarizable
      force fields, namely, the Gaussian electrostatic model (GEM), a model based on
      density fitting, which uses fitted electronic densities to evaluate nonbonded
      interactions, and SIBFA (sum of interactions between fragments ab initio
      computed), which resorts to distributed multipoles. To understand the benefits of
      the use of Gaussian electrostatics, we evaluate first the accuracy of GEM, which
      is a pure density-based Gaussian electrostatics model on a test Ca(II)-H2O
      complex. GEM is shown to further improve the agreement of MM polarization with ab
      initio reference results. Indeed, GEM introduces nonclassical effects by modeling
      the short-range quantum behavior of electric fields and therefore enables a
      straightforward (and selective) inclusion of the sole overlap-dependent exchange
      polarization repulsive contribution by means of a Gaussian damping function
      acting on the GEM fields. The S/G-1 scheme is then introduced. Upon limiting the
      use of Gaussian electrostatics to metal centers only, it is shown to be able to
      capture the dominant quantum effects at play on the metal coordination sphere.
      S/G-1 is able to accurately reproduce ab initio total interaction energies within
      closed-shell metal complexes regarding each individual contribution including the
      separate contributions of induction, polarization, and charge-transfer.
      Applications of the method are provided for various systems including the HIV-1
      NCp7-Zn(II) metalloprotein. S/G-1 is then extended to heavy metal complexes.
      Tested on Hg(II) water complexes, S/G-1 is shown to accurately model polarization
      up to quadrupolar response level. This opens up the possibility of embodying
      explicit scalar relativistic effects in molecular mechanics thanks to the direct
      transferability of ab initio pseudopotentials. Therefore, incorporating GEM-like
      electron density for a metal cation enable the introduction of nonambiguous short
      range quantum effects within any point-dipole based polarizable force field
      without the need of an extensive parametrization. 

PMID- 24878002
TI  - A dual luciferase system for analysis of post-transcriptional regulation of gene
      expression in Leishmania.
AB  - Gene expression in kinetoplastid parasites is regulated via post-transcriptional
      mechanisms that modulate mRNA turnover, translation rate, and/or post
      translational protein stability. To facilitate the analysis of post
      transcriptional regulation, a dual luciferase system was developed in which
      firefly and Renilla luciferase reporters genetically fused to compatible drug
      resistance genes are integrated in place of one allele of the gene of interest
      and of an internal control gene, respectively, in a manner that preserves the
      cognate pre-mRNA processing signals. The sensitivity and reproducibility of the
      assay coupled with the ability to rapidly assemble reporter integration
      constructs render the dual luciferase system suitable for analysis of multiple
      candidates derived from global expression analysis platforms. To demonstrate the
      utility of the system, regulation of three genes in response to purine starvation
      was examined in Leishmania donovani promastigotes. This dual luciferase system
      should be directly applicable to the analysis of post-transcriptional regulation
      in other kinetoplastids. 

PMID- 24878004
TI  - Occupational performance and strategies for managing daily life among the elderly
      with heart failure.
AB  - AIM: The aim of this study was to describe experiences of limitations in
      occupational performance and strategies for managing daily activities among the
      elderly with chronic heart failure (CHF). METHODS: Ten participants from primary
      healthcare with a confirmed diagnosis of CHF were interviewed. The interviews
      were analysed using qualitative content analysis. RESULTS: The first theme,
      "Redefining an active life, aware of one's impaired body", was based on four sub
      themes: realizing one's limited activity ability; striving to preserve an active
      life; focusing on meaningful activities; and changing vs. not changing habits and
      roles. The second theme, "Planning activities and balancing the degree of
      effort", was based on three sub-themes: limiting, organizing, and rationalizing
      activities; adjusting activities to today's ability; and using technology and
      adapting the environment. CONCLUSIONS: Elderly people with CHF are struggling
      with an ongoing process of occupational adaptation due to periodical physical
      decline and fluctuating day-to-day ability. This highlights a need for
      information on strategies from a holistic perspective and client-centred
      occupational therapy interventions.

PMID- 24878005
TI  - Treatment of Bartter syndrome. Unsolved issue.
AB  - OBJECTIVE: To describe the results of a long-term follow-up of Bartter syndrome
      patients treated with different drugs. METHOD: Patients were diagnosed according
      to clinical and laboratory data. Treatment protocol was potassium
      supplementation, sodium, spironolactone, and non-steroidal anti-inflammatory
      drug. Patients who developed proteinuria were converted to angiotensin conversion
      enzyme inhibitor. The variables evaluated for each drug were Z-score for weight
      and stature, proteinuria, creatinine clearance, gastrointestinal complaints,
      amount of potassium supplementation, serum potassium and bicarbonate levels, and
      findings of upper digestive endoscopy. RESULTS: 20 patients were included. Follow
      up was 10.1 +/- 5.2 years. 17 patients received indomethacin for 5.9 +/- 5.3
      years; 19 received celecoxib, median of 35 months; and five received enalapril,
      median of 23 months. During indomethacin, a statistically significant increase
      was observed in the Z-score for stature and weight, without a change in the
      creatinine clearance. Seven of 17 patients had gastrointestinal symptoms, and
      upper digestive endoscopy evidenced gastritis in three patients and gastric ulcer
      in four patients. During celecoxib use, a significant increase was detected in
      the Z-score for stature and weight and a reduction of hyperfiltration; seven
      patients presented gastrointestinal symptoms, and upper digestive endoscopy
      evidenced mild gastritis in three. During enalapril use, no significant changes
      were observed in the Z-score for stature, weight and creatinine clearance. The
      conversion to enalapril resulted in a significant reduction in proteinuria.
      CONCLUSION: The authors suggest starting the treatment with celecoxib, and
      replacing by ACEi if necessary, monitoring the renal function. The safety and
      efficacy of celecoxib need to be assessed in larger controlled studies.

PMID- 24878006
TI  - Outcome of children with severe acquired aplastic anemia treated with rabbit
      antithymocyte globulin and cyclosporine A.
AB  - OBJECTIVE: To evaluate the outcome of children with severe acquired aplastic
      anemia treated with rabbit antithymocyte globulin and cyclosporine as first-line
      treatment at this institution. METHODS: Retrospective analysis of 26 pediatric
      patients with aplastic anemia, treated between 1996 and 2011 with rabbit
      antithymocyte globulin plus cyclosporine. RESULTS: The overall response rate at
      six months was 34.6% (9/26), and the cumulative incidence of relapse was 26.5%
      (95% confidence interval [CI]: 1.4%-66%) at 5 years. The cumulative incidence of
      clonal evolution after immunosuppressive therapy was 8.3% (95% CI: 0.001%-53.7%)
      at five years with both clonal evolutions in non -responders who acquired
      monosomy 7 karyotype. The overall survival at five years was 73.6% (95% CI: 49.2%
      87.5%). CONCLUSIONS: The present results confirm the poor response rate with
      rabbit antithymocyte globulin as first therapy in pediatrics patients, similar to
      what has been reported for patients of all ages. This confirmation is problematic
      in Brazil, given the lack of horse antithymocyte globulin in many markets outside
      the United States.

PMID- 24878009
TI  - Team-based health care in pathology training programs.

PMID- 24878007
TI  - Effects of erythromycin on gamma-glutamyl cysteine synthetase and interleukin
      1beta in hyperoxia-exposed lung tissue of premature newborn rats.
AB  - OBJECTIVE: To explore the effect of erythromycin on hyperoxia-induced lung
      injury. METHODS: One-day-old preterm offspring Sprague-Dawley (SD) rats were
      randomly divided into four groups: group 1, air + sodium chloride; group 2, air +
      erythromycin;group 3, hyperoxia + sodium chloride; and group 4, hyperoxia +
      erythromycin. At one, seven, and 14 days of exposure, glutathione (GSH) and
      interleukin-1 beta (IL-1 beta) were detected by double-antibody sandwich enzyme
      linked immunosorbent assay (ELISA), and bicinchoninic acid (BCA) was used to
      detect GSH protein. gamma-glutamine-cysteine synthetase (gamma-GCS) mRNA was
      detected by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS:
      Compared with group 1, expressions of GSH and gamma-GCS mRNA in group 3 were
      significantly increased at one and seven days of exposure (p < 0.05), but
      expression of gamma-GCS mRNA was significantly reduced at 14 days; expression of
      IL-1 beta in group 3 was significantly increased at seven days of exposure (p <
      0.05), and was significantly reduced at 14 days. Compared with group 3,
      expressions of GSH and gamma-GCS mRNA in group 4 were significantly increased at
      one, seven, and 14 days of exposure (p < 0.05), but expressions of GSH showed a
      downward trend at 14 days; expression of IL-1 beta in group 4 was significantly
      reduced at one and seven days of exposure (p < 0.05). CONCLUSIONS: Changes in
      oxidant-mediated IL-1 beta and GSH are involved in the development of hyperoxia
      induced lung injury. Erythromycin may up-regulate the activity of gamma-GCS,
      increasing the expression of GSH, inhibiting the levels of oxidant-mediated IL-1
      beta and alleviating hyperoxia-induced lung injury via an antioxidant effect.

PMID- 24878008
TI  - TLR-2 and TLR-4 expression in monocytes of newborns with late-onset sepsis.
AB  - OBJECTIVE: To analyze toll-like receptor (TLR)-2 and TLR-4 expression in
      monocytes of newborns with late-onset sepsis. METHODS: This prospective study
      included 27 full-term newborns aged 8 to 29 days, with clinical and laboratory
      diagnosis of late-onset sepsis. Ten newborns (37%) had positive cultures.
      Cytokines were measured by cytometric bead array in peripheral blood, while TLR
      2, TLR-4 expression, and median fluorescence intensity (MFI) were determined by
      immunophenotyping peripheral whole blood monocytes, and were analyzed with a BD
      FACSDiva flow cytometer (Becton, Dickinson and Company, USA). A comparison was
      performed with healthy adults. RESULTS: Microorganisms were identified in 37% of
      these septic newborns, and all of them had high levels of pro-inflammatory
      cytokines (IL-8, IL-6, IL-1beta) and anti-inflammatory cytokine (IL-10)
      corroborating the inflammatory/septic process. In monocytes, the frequency of TLR
      4 expression was higher in infected newborns (p = 0.01). CONCLUSION: This study
      investigated the innate immune response in septic newborns. Septic newborns that
      relied almost exclusively on the innate immune system showed little in vivo
      response at monocyte activation, suggesting impaired immune response and
      increased susceptibility to infection.

PMID- 24878010
TI  - The assessment of C-reactive protein does not improve the diagnosis of myocardial
      infarction using a high-sensitivity troponin immunoassay.

PMID- 24878011
TI  - Rebooting the pathology journal: learning in the age of digital pathology.

PMID- 24878012
TI  - An introduction to molecular pathology of the head and neck.

PMID- 24878013
TI  - Squamous cell carcinoma variants of the upper aerodigestive tract: a
      comprehensive review with a focus on genetic alterations.
AB  - CONTEXT: Squamous cell carcinoma of the upper aerodigestive tract is a
      heterogenous entity. Although conventional squamous cell carcinomas are easily
      recognized, the morphologic variants of squamous cell carcinoma can present a
      diagnostic challenge. Familiarity with these variants is necessary because many
      are associated with unique risk factors and are characterized by specific
      molecular alterations (eg, nuclear protein in testis midline carcinomas). Perhaps
      the most important distinction is in identifying viral-related from nonviral
      related carcinomas. The accurate diagnosis of these variants is necessary for
      prognostic and therapeutic reasons. OBJECTIVES: To provide a clinicopathologic
      overview and summary of the molecular alterations of the common squamous cell
      carcinoma variants, including verrucous, spindle cell, acantholytic,
      adenosquamous, basaloid, and papillary squamous cell carcinoma, as well as
      nuclear protein in testis midline carcinoma, and to discuss the distinguishing
      features of human papillomavirus- and Epstein-Barr virus-related squamous cell
      carcinomas. DATA SOURCES: Published peer-reviewed literature. CONCLUSIONS:
      Familiarity with squamous cell carcinoma variants is essential for proper
      diagnosis and to guide appropriate clinical management. Further insight into the
      molecular alterations underlying those variants may lead to alterations in
      existing treatment approaches and to evolution of novel treatment modalities.

PMID- 24878014
TI  - The molecular genetics of inflammatory, autoimmune, and infectious diseases of
      the sinonasal tract: a review.
AB  - CONTEXT: The sinonasal tract is frequently affected by a variety of nonneoplastic
      inflammatory disease processes that are often multifactorial in their etiology
      but commonly have a molecular genetic component. OBJECTIVE: To review the
      molecular genetics of a variety of nonneoplastic inflammatory diseases of the
      sinonasal tract. DATA SOURCES: Inflammatory lesions of the sinonasal tract can be
      divided into 3 main categories: (1) chronic rhinosinusitis, (2) infectious
      diseases, and (3) autoimmune diseases/vasculitides. The molecular diagnosis and
      pathways of a variety of these inflammatory lesions are currently being
      elucidated and will shed light on disease pathogenesis and treatment.
      CONCLUSIONS: The sinonasal tract is frequently affected by inflammatory lesions
      that arise through complex interactions of environmental, infectious, and genetic
      factors. Because these lesions are all inflammatory in nature, the molecular
      pathology surrounding them is most commonly due to upregulation and down
      regulation of genes that affect inflammatory responses and immune regulation.

PMID- 24878015
TI  - An overview of molecular and genetic alterations in selected benign odontogenic
      disorders.
AB  - CONTEXT: Some dental abnormalities have environmental causes. Other odontogenic
      alterations are idiopathic and may have hereditary etiologies. Investigations of
      these conditions are ongoing. OBJECTIVE: To provide a discussion of developmental
      odontogenic abnormalities and benign odontogenic overgrowths and neoplasms for
      which genetic alterations have been well demonstrated and well documented. DATA
      SOURCES: Relevant peer-reviewed literature. CONCLUSIONS: The understanding of
      benign odontogenic lesions at a molecular level is rather well developed for some
      lesions and at the initial stages for many others. Further characterization of
      the molecular underpinnings of these and other odontogenic lesions would result
      in an enhanced comprehension of odontogenesis and the pathogenesis of a variety
      of odontogenic aberrations. These advancements may lead to better prevention and
      treatment paradigms and improved patient outcomes.

PMID- 24878016
TI  - Molecular pathology of skin neoplasms of the head and neck.
AB  - CONTEXT: Skin neoplasms include the most common malignancies affecting humans.
      Many show an ultraviolet (UV)-induced pathogenesis and often affect the head and
      neck region. OBJECTIVE: To review literature on cutaneous neoplasms that show a
      predilection for the head and neck region and that are associated with molecular
      alterations. DATA SOURCES: Literature review. CONCLUSIONS: Common nonmelanoma
      skin cancers, such as basal and squamous cell carcinomas, show a UV-induced
      pathogenesis. Basal cell carcinomas are characterized by molecular alterations of
      the Hedgehog pathway, affecting patched and smoothened genes. While squamous cell
      carcinomas show UV-induced mutations in several genes, driver mutations are only
      beginning to be identified. In addition, certain adnexal neoplasms also
      predominantly affect the head and neck region and show interesting, recently
      discovered molecular abnormalities, or are associated with hereditary conditions
      whose molecular genetic pathogenesis is well understood. Furthermore, recent
      advances have led to an increased understanding of the molecular pathogenesis of
      melanoma. Certain melanoma subtypes, such as lentigo maligna melanoma and
      desmoplastic melanoma, which are more often seen on the chronically sun-damaged
      skin of the head and neck, show differences in their molecular signature when
      compared to the other more common subtypes, such as superficial spreading
      melanoma, which are more prone to occur at sites with acute intermittent sun
      damage. In summary, molecular alterations in cutaneous neoplasms of the head and
      neck are often related to UV exposure. Their molecular footprint often reflects
      the histologic tumor type, and familiarity with these changes will be
      increasingly necessary for diagnostic and therapeutic considerations.

PMID- 24878017
TI  - Utility of repeat testing of critical values: a Q-probes analysis of 86 clinical
      laboratories.
AB  - CONTEXT: A common laboratory practice is to repeat critical values before
      reporting the test results to the clinical care provider. This may be an
      unnecessary step that delays the reporting of critical test results without
      adding value to the accuracy of the test result. OBJECTIVES: To determine the
      proportions of repeated chemistry and hematology critical values that differ
      significantly from the original value as defined by the participating laboratory,
      to determine the threshold differences defined by the laboratory as clinically
      significant, and to determine the additional time required to analyze the repeat
      test. DESIGN: Participants prospectively reviewed critical test results for 4
      laboratory tests: glucose, potassium, white blood cell count, and platelet count.
      Participants reported the following information: initial and repeated test
      result; time initial and repeat results were first known to laboratory staff;
      critical result notification time; if the repeat result was still a critical
      result; if the repeat result was significantly different from the initial result,
      as judged by the laboratory professional or policy; significant difference
      threshold, as defined by the laboratory; the make and model of the instrument
      used for primary and repeat testing. RESULTS: Routine, repeat analysis of
      critical values is a common practice. Most laboratories did not formally define a
      significant difference between repeat results. Repeated results were rarely
      considered significantly different. Median repeated times were at least 17 to 21
      minutes for 10% of laboratories. Twenty percent of laboratories reported at least
      1 incident in the last calendar year of delayed result reporting that clinicians
      indicated had adversely affected patient care. CONCLUSION: Routine repeat
      analysis of automated chemistry and hematology critical values is unlikely to be
      clinically useful and may adversely affect patient care.

PMID- 24878018
TI  - Immunohistochemistry, fluorescence in situ hybridization, and reverse
      transcription-polymerase chain reaction for the detection of anaplastic lymphoma
      kinase gene rearrangements in patients with non-small cell lung cancer: potential
      advantages and methodologic pitfalls.
AB  - CONTEXT: Echinoderm microtubule-associated protein-like 4 gene (EML4) and
      anaplastic lymphoma kinase gene (ALK) fusion was shown to be the driver of
      tumorigenesis in approximately 3% to 5% of patients with non-small cell lung
      cancer (NSCLC) and is associated with response to inhibition with crizotinib.
      However, no complete agreement regarding the best diagnostic test for
      identification of ALK rearrangements has been achieved yet. OBJECTIVE: To
      investigate the concordance, sensitivity, and specificity of immunohistochemistry
      (IHC), fluorescence in situ hybridization (FISH), and reverse transcription
      polymerase chain reaction (RT-PCR) for detection of ALK rearrangements. DESIGN:
      Thirty-six prospectively tested patients with NSCLC who had adenocarcinoma and 10
      ALK-positive samples were included in the study. All samples were tested by IHC
      (ALK1 clone, 5A4 clone, D5F3 clone), FISH (LSI ALK Break Apart and ALK FISH
      Probe), and multiplexed RT-PCR. RESULTS: Immunohistochemistry staining was
      successful in all samples.. Clone D5F3 showed the best sensitivity and
      specificity of 100%; clones ALK1 and 5A4 showed sensitivities of 91% with
      specificity of 100%. Both FISH probes showed concordance with sensitivity and
      specificity of 100%. Hybridization and RT-PCR were successful in 98% and 93.4% of
      samples, respectively, with sensitivity of 88% and specificity of 100%. Frequent
      artifacts leading to misinterpretation were observed with all 3 methodologies.
      CONCLUSIONS: All 3 methodologies showed good sensitivity, specificity, and
      concordance, when artifacts were characterized and excluded. However, all
      ambiguous cases have to be confirmed as ALK rearranged by at least 2 of the 3
      methods.

PMID- 24878019
TI  - Creation of 3-dimensional prostate cancer maps: methodology and clinical and
      research implications.
AB  - CONTEXT: The creation of 3-dimensional prostate cancer maps could assist with
      surgical intervention, radiotherapy treatment planning and for correlative
      pathology-imaging research. OBJECTIVES: To develop methodology for creating
      detailed, 3-dimensional, prostate cancer maps (3DPCM) of tumor location, extra
      prostatic extension sites, and positive margins and to assess the adequacy of
      current clinical target volumes for postoperative radiotherapy to the prostate
      using 3DPCM coregistered with preoperative magnetic resonance imaging. DESIGN:
      Parallel slices of prostatectomy specimens were created with ProCUT, and 2
      dimensional cancer maps were generated as line diagrams after microscopic
      examination of each slice. The 2-dimensional cancer maps were aligned and stacked
      to create a 3DPCM, which was coregistered with the preoperative magnetic
      resonance imaging scan. The map was exported to the radiotherapy planning system
      and was used to determine the areas at greater risk, which were then compared
      against the current Radiation Therapy Oncology Group guidelines for contouring
      postoperative clinical target volumes to assess the adequacy of coverage.
      RESULTS: Twenty-eight patients with a mean age of 66 years (range, 52-73)
      underwent radical prostatectomy and postoperative radiotherapy. Seventeen
      patients (61%) received adjuvant radiotherapy for pT3 disease and/or positive
      margins, and the rest underwent salvage radiotherapy. Thirty-nine percent (11 of
      28) of the patients had Gleason scores of 8 or 9. The contours based on the
      Radiation Therapy Oncology Group guidelines for postoperative radiotherapy
      resulted in inadequate coverage of extraprostatic extensions in 79% (22 of 28)
      and positive margins in 64% (18 of 28) of the cases. CONCLUSIONS: We have
      developed a methodology for creation of 3DPCM. Modification of the radiotherapy
      contours, based on the 3DPCM coregistered with pretreatment magnetic resonance
      imaging, covers the areas at high risk of recurrence. The 3DPCM could become an
      important clinical and research tool for urologists, pathologists, radiologists,
      and oncologists.

PMID- 24878020
TI  - Development and initial validation of a project-based rubric to assess the
      systems-based practice competency of residents in the clinical chemistry rotation
      of a pathology residency.
AB  - CONTEXT: Systems-based practice (SBP) is 1 of 6 core competencies required in all
      resident training programs accredited by the Accreditation Council for Graduate
      Medical Education. Reliable methods of assessing resident competency in SBP have
      not been described in the medical literature. OBJECTIVE: To develop and validate
      an analytic grading rubric to assess pathology residents' analyses of SBP
      problems in clinical chemistry. DESIGN: Residents were assigned an SBP project
      based upon unmet clinical needs in the clinical chemistry laboratories. Using an
      iterative method, we created an analytic grading rubric based on critical
      thinking principles. Four faculty raters used the SBP project evaluation rubric
      to independently grade 11 residents' projects during their clinical chemistry
      rotations. Interrater reliability and Cronbach alpha were calculated to determine
      the reliability and validity of the rubric. Project mean scores and range were
      also assessed to determine whether the rubric differentiated resident critical
      thinking skills related to the SBP projects. RESULTS: Overall project scores
      ranged from 6.56 to 16.50 out of a possible 20 points. Cronbach alpha ranged from
      0.91 to 0.96, indicating that the 4 rubric categories were internally consistent
      without significant overlap. Intraclass correlation coefficients ranged from 0.63
      to 0.81, indicating moderate to strong interrater reliability. CONCLUSIONS: We
      report development and statistical analysis of a novel SBP project evaluation
      rubric. The results indicate the rubric can be used to reliably assess pathology
      residents' critical thinking skills in SBP.

PMID- 24878021
TI  - Touch preparations for the intraoperative evaluation of sentinel lymph nodes
      after neoadjuvant therapy have high false-negative rates in patients with breast
      cancer.
AB  - CONTEXT: The use of a touch preparation for intraoperative sentinel lymph node
      diagnosis has become a preferred method of many pathologists because of its
      reported high sensitivity and rapid turnaround time. However, after neoadjuvant
      chemotherapy many lymph nodes have significant treatment-related changes that may
      affect the diagnostic accuracy of the intraoperative evaluation. OBJECTIVE: To
      determine the accuracy of touch preparation for the intraoperative diagnosis of
      metastatic breast carcinoma in the neoadjuvant setting. DESIGN: We reviewed
      retrospectively the results of intraoperative evaluations for 148 different
      sentinel lymph nodes from 63 patients who had undergone neoadjuvant chemotherapy
      for invasive breast cancer at our institution. The intraoperative touch
      preparation results were compared with the final pathology reports in conjunction
      with relevant clinical data. RESULTS: Use of touch preparation for the evaluation
      of sentinel lymph nodes intraoperatively after neoadjuvant therapy was associated
      with a low sensitivity of 38.6% (95% confidence interval [CI], 24.4-54.5) but
      high specificity of 100% (95% CI, 96.5-100). There was no difference in
      sensitivity rates between cytopathologists and noncytopathologists in this cohort
      (P = .40). Patients with invasive lobular carcinoma and those who had a
      clinically positive axilla before the initiation of neoadjuvant therapy were the
      most likely to have a false-negative result at surgery. CONCLUSIONS:
      Intraoperative touch preparations should not be used alone for the evaluation of
      sentinel lymph nodes in the setting of neoadjuvant therapy for breast cancer
      because of low overall sensitivity.

PMID- 24878022
TI  - beta-Globin gene sequencing of hemoglobin Austin revises the historically
      reported electrophoretic migration pattern.
AB  - CONTEXT: Hemoglobin (Hb) Austin was defined in 1977, using amino acid sequencing
      of samples from 3 unrelated Mexican-Americans, as a substitution of serine for
      arginine at position 40 of the beta-globin chain (Arg40Ser). Its electrophoretic
      migration on both cellulose acetate (pH 8.4) and citrate agar (pH 6.2) was
      reported between Hb F and Hb A, and this description persists in reference
      literature. OBJECTIVES.-To review the clinical features and redefine the
      diagnostic characteristics of Hb Austin. DESIGN: Eight samples from 6 unrelated
      individuals and 2 siblings, all with Hispanic surnames, were submitted for
      abnormal Hb identification between June 2010 and September 2011. High-performance
      liquid chromatography, isoelectric focusing (IEF), citrate agar electrophoresis,
      and bidirectional DNA sequencing of the entire beta-globin gene were performed.
      RESULTS: DNA sequencing confirmed all 8 individuals to be heterozygous for Hb
      Austin (Arg40Ser). Retention time on high-performance liquid chromatography and
      migration on citrate agar electrophoresis were consistent with that
      identification. Migration on IEF, however, was not between Hb F and Hb A, as
      predicted from the report of cellulose acetate electrophoresis. By IEF, Hb Austin
      migrated anodal to ("faster than") Hb A. CONCLUSIONS: Hemoglobin Austin
      (Arg40Ser) appears on IEF as a "fast," anodally migrating, Hb variant, just as
      would be expected from its amino acid substitution. The cited historic report is,
      at best, not applicable to IEF and is probably erroneous. Our observation of 8
      cases in 16 months suggests that this variant may be relatively common in some
      Hispanic populations, making its recognition important. Furthermore, gene
      sequencing is proving itself a powerful and reliable tool for definitive
      identification of Hb variants.

PMID- 24878023
TI  - Loss of heterozygosity and microsatellite instability are rare in sporadic
      dedifferentiated liposarcoma: a study of 43 well-characterized cases.
AB  - CONTEXT: Defects in mismatch repair proteins have been identified in Lynch
      syndrome-associated liposarcomas, as well as in rare sporadic sarcomas. However,
      it is unclear if mismatch repair defects have a role in sarcoma tumorigenesis.
      Microsatellite instability is a surrogate marker of mismatch repair defects.
      OBJECTIVES: To determine whether sporadic dedifferentiated liposarcomas display
      microsatellite instability and, if so, to evaluate whether such instability
      differs between the lipogenic and nonlipogenic components of these tumors.
      DESIGN: The diagnoses of conventional dedifferentiated liposarcoma were confirmed
      by a combination of morphologic, immunophenotypic, and molecular studies.
      Standard fluorescence-based polymerase chain reaction, including 5 mononucleotide
      microsatellite markers (BAT25, BAT26, NR21, NR24, and MONO27), as well as 2
      pentanucleotide repeat markers (Penta C and Penta D), was used to test for
      instability and loss of heterozygosity. RESULTS: We demonstrated only a single
      case (1 of 43) with microsatellite instability at one mononucleotide marker. No
      sarcomas showed high-level microsatellite instability. However, loss of
      heterozygosity at the pentanucleotide markers was observed in 8 of 43 cases. The
      presence of loss of heterozygosity was overrepresented in the nonlipogenic
      (dedifferentiated) components compared with the paired lipogenic (well
      differentiated) components. CONCLUSIONS: Mismatch repair defects do not
      contribute to sporadic dedifferentiated liposarcoma tumorigenesis. Whether the
      observed loss of heterozygosity drives tumorigenesis in liposarcoma, for example
      by affecting tumor suppressor or cell cycle regulator genes, remains to be
      determined.

PMID- 24878024
TI  - Study of circulating microRNA-125b levels in serum exosomes in advanced melanoma.
AB  - CONTEXT: Malignant melanoma is an aggressive tumor that produces exosomes, which
      contain microRNAs (miRNAs) that could be of utility in following tumoral cell
      dysregulation. MicroR-125b is a miRNA whose down-regulation seems to be
      implicated in melanoma progression. OBJECTIVE: To analyze miR-125b levels in
      serum, and in exosomes obtained from serum, from patients with advanced melanoma.
      DESIGN: Serum samples were obtained from 21 patients with advanced melanoma, from
      16 disease-free patients with melanoma, and from 19 healthy volunteers. Exosomes
      were isolated from serum by precipitation, and miR-16 and miR-125b levels were
      quantified by real-time polymerase chain reaction. RESULTS: MicroR-16, but not
      miR-125b, was detected in all samples, and miR-16 levels were significantly
      higher in serum than they were in exosomes. MicroR-16 expression levels did not
      differ significantly between the 2 groups (patients with melanoma and healthy
      donors). There was a significant relationship between miR-125b and miR-16 levels
      in exosomes. Additionally, miR-125b levels in exosomes were significantly lower
      in patients with melanoma compared with disease-free patients with melanoma and
      healthy controls. CONCLUSIONS: Exosomes can provide a suitable material to
      measure circulating miRNA in melanoma, and miR-16 can be used as an endogenous
      normalizer. Lower levels of miR-125b in exosomes obtained from serum are
      associated with advanced melanoma disease, probably reflecting the tumoral cell
      dysregulation.

PMID- 24878025
TI  - Sudden cardiac death due to coronary artery involvement by IgG4-related disease:
      a rare, serious complication of a rare disease.
AB  - Immunoglobulin G4-related disease (IgG4-RD) is a systemic disorder characterized
      by multiorgan fibrosis with IgG4-producing plasma cells, increased IgG4 serum
      concentration, and responsiveness to steroid therapy. Involvement of the
      pancreas, salivary glands, orbit, aorta, and other sites has been well documented
      in the literature; however, there have been limited reports of cases involving
      the coronary arteries. We report the case of a 53-year-old Hispanic man who was
      brought to the emergency center and diagnosed with sudden cardiac death. Autopsy
      was subsequently performed, revealing multiorgan involvement by IgG4-RD,
      including involvement of the coronary arteries. The inflammation and fibrosis, in
      combination with concomitant atherosclerotic disease, resulted in severe stenosis
      of the coronary arteries. Two of the coronary arteries were further occluded by
      thrombosis. These factors led to cardiac hypoperfusion, myocardial infarction
      and, ultimately, sudden cardiac death. Fatal involvement of the coronary arteries
      has not been previously reported, raising a new concern for a severe complication
      of IgG4-RD. 

PMID- 24878026
TI  - Fatal spontaneous Clostridium septicum gas gangrene: a possible association with
      iatrogenic gastric acid suppression.
AB  - The long-term use of proton pump inhibitors has been linked to an increased risk
      for the development of gastric polyps, hip fractures, pneumonia, and Clostridium
      difficile colitis. There is evidence that chronic acid suppression from long-term
      use of proton pump inhibitors poses some risk for the development of C difficile
      associated diarrhea by decreasing the elimination of pathogenic microbes before
      reaching the lower gastrointestinal tract. Here we present a case of a 51-year
      old woman with a recent history of abdominal pain and fever who presented to the
      emergency department with rapidly progressive spontaneous necrotizing fasciitis
      and gas gangrene and died within hours of presentation. Postmortem examination
      confirmed spreading tissue gas gangrene and myonecrosis. In addition, multiple
      intestinal ulcers containing Clostridium septicum were present at autopsy. This
      case illustrates a possible association between proton pump inhibitor therapy and
      fatal C septicum infection. 

PMID- 24878027
TI  - Breast implant-associated anaplastic large cell lymphoma: review of a distinct
      clinicopathologic entity.
AB  - Primary breast anaplastic large cell lymphoma (ALCL) is rare but is more commonly
      seen in patients with implants; fewer than 50 cases of breast implant-associated
      ALCL have been reported in the English language literature. Breast implant
      associated ALCL is not a disease of the breast parenchyma, but instead is a
      disease of the fibrous capsule surrounding the implant. The patients usually
      present with an effusion around the implant and, rarely, with a solid mass.
      Morphologically, the neoplastic cells are large, epithelioid, and pleomorphic,
      with abundant cytoplasm, vesicular irregular nuclei, and frequent mitoses.
      Occasional "hallmark" cells may be present. The lesional cells typically show
      strong and diffuse immunoreactivity for CD30 and often express T-cell markers,
      cytotoxic-associated antigens, and epithelial membrane antigen. Almost all
      reported cases are negative for anaplastic lymphoma kinase. Molecular genetic
      analyses have demonstrated T-cell receptor gene rearrangements. The differential
      diagnosis essentially includes poorly differentiated carcinoma, other lymphomas,
      and chronic inflammation. Once a diagnosis of lymphoma is established, it is
      important to exclude systemic anaplastic lymphoma kinase-negative ALCL involving
      the breast, primary cutaneous ALCL, and other CD30(+) lymphoproliferative
      disorders. The patients with effusion-associated ALCL often have an indolent
      course and excellent prognosis, responding well to excision of the fibrous
      capsule around the implant (capsulectomy) and implant removal. In contrast,
      patients who present with a distinct mass may have a more aggressive course and
      poor prognosis, requiring chemotherapy and/or radiation therapy. 

PMID- 24878028
TI  - Copper(II) sequentially loads onto the N-terminal amino group of the cellular
      prion protein before the individual octarepeats.
AB  - The cellular prion protein (PrPC) binds to Cu2+ ions in vivo, and a misfolded
      form of PrPC is responsible for a range of transmissible spongiform
      encephalopathies. Recently, disruption of Cu2+ homeostasis in mice has been shown
      to impart resistance to scrapie infection. Using full-length PrPC and model
      peptide fragments, we monitor the sequential loading of Cu2+ ions onto PrPC using
      visible circular dichroism. We show the N-terminal amino group of PrPC is not the
      principal binding site for Cu2+; however, surprisingly, it has an affinity for
      Cu2+ tighter than that of the individual octarepeat binding sites present within
      PrPC. We re-evaluate what is understood about the sequential loading of Cu2+ onto
      the full-length protein and show for the first time that Cu2+ loads onto the N
      terminal amino group before the single octarepeat binding sites.

PMID- 24878029
TI  - Time-resolved spectra from millivolt EELS data.
AB  - The millivolt energy resolution now obtainable in electron energy-loss spectra
      (EELS) on the latest monochromated scanning transmission electron microscope
      corresponds, via the uncertainty principle, to a time range of 414 fs (for 10 meV
      resolution), and a time resolution of 0.138 fs (for energy range of 30 eV).
      (Thus, the width of an EELS peak is inversely related to the lifetime of an
      excitation.) This compares favorably with the latest X-ray free electron lasers.
      The time evolution of a Drude-Lorentz oscillator may be obtained from an EELS
      using logarithmic deconvolution followed by Kramers-Kronig analysis to extract
      the frequency-dependent dielectric function, and a final Fourier transform from
      frequency to time domain. This time-dependent dielectric function was interpreted
      as the impulse response of electrons, phonons, or ions based on the Drude-Lorentz
      theory. The time evolution of electronic oscillators from ice and protein,
      extracted from low resolution experimental data, were compared. Using higher
      energy resolution data we have also extracted the time-resolved spectra from
      excitons in an alkali halide, BaF2. Despite the small scanning transmission
      electron microscope probe size, delocalization limits the spatial resolution to
      about 50 nm, which is, nevertheless, better than the millimeter resolution of
      infrared absorption spectroscopy or Raman spectroscopy. 

PMID- 24878030
TI  - Pre-hospital evaluation of electrocardiographic grade 3 ischemia predicts infarct
      progression and final infarct size in ST elevation myocardial infarction patients
      treated with primary percutaneous coronary intervention.
AB  - BACKGROUND: In STEMI, grade-3 ischemia (G3) on admission ECG predicts larger
      infarct size (IS) than grade-2 (G2). We evaluated whether pre-hospital G3 and its
      temporal behavior are associated with IS and salvage after pPCI. METHODS: In 401
      STEMI patients, pre-hospital and pre-PCI ECGs were classified as G3 or G2. IS was
      assessed by single-photon emission computed tomography (SPECT) at 30days. In 245
      patients, pre-PCI SPECT was available to determine myocardium at risk (MaR).
      RESULTS: G3 criteria were met by 88, and G2 by 313 patients. G3 was independently
      associated with IS (p=0.006). With ST resolution (STR) group as a reference, G2
      >G2, G2->G3 and G3->G3 were associated with larger IS (B=4.4, p=0.004; B=5.4,
      p=0.01; B=10.2, p<0.001, respectively), whereas G3->G2 was not. Salvage was
      similar between G3 and G2 on pre-hospital ECG if treated early, however lower for
      G3 when treated later (>2.5h); 48% (35-78) vs 62% (40-87); p=0.04. CONCLUSION:
      Development or persistence of G3 is associated with larger IS and less salvage,
      but decreasing grade G3->G2 was not.

PMID- 24878031
TI  - The origin of monitoring of acute myocardial infarction with continuous
      vectorcardiography.
AB  - The continuous change of the ST and QRS vectorcardiograms reflect the underlying
      ischemic event, and can be used as a tool in the management of the acute event.
      It also reflects reperfusion, and can guide the clinician on when and how to
      intervene. Continuous vectorcardiography has proven to add prognostic
      information, both in the acute phase (can be used already in the ambulance during
      transportation to CCU) and after discharge from hospital. This paper reviews the
      origin of continous vectorcardiography as a monitoring device in AMI, including
      the follow-up research until today. 

PMID- 24878032
TI  - The stability of myocardial area at risk estimated electrocardiographically in
      patients with ST elevation myocardial infarction.
AB  - In patients with ST-elevation myocardial infarction (STEMI) the amount of
      myocardial area at risk (MaR) indicates the maximal potential loss of myocardium
      if the coronary artery remains occluded. During the time course of infarct
      evolution ischemic MaR is replaced by necrosis, which results in a decrease in ST
      segment elevation and QRS complex distortion. Recently it has been shown that
      combining the electrocardiographic (ECG) Aldrich ST and Selvester QRS scores
      result in a more accurate estimate of MaR than using either method alone.
      Therefore, we hypothesized that the combined Aldrich and Selvester score,
      indicating MaR, is stable until myocardial reperfusion therapy. In a
      retrospective analysis of a study population of 114 patients, 33 patients were
      included. The combined Aldrich and Selvester score was determined in ECGs
      recorded in the ambulance (ECG1) and in the hospital before reperfusion (ECG2).
      The combined Aldrich and Selvester score was considered stable if the difference
      between ECG1 and ECG2 was <4.5-percentage point. Stability of the combined
      Aldrich and Selvester score was observed in 12/33 patients (36.4%), and in
      regards to anterior and inferior ST elevation in 4/14 patients (28.6%) and 8/19
      patients (42.1%), respectively. The median time between the recording of ECG1 and
      ECG2 was 75 minutes, however the changes in ECG scores were independent of the
      time between ECG recordings. Patients not meeting the stability criterion either
      had a decrease (9 patients) or increase (12 patients) of the combined Aldrich and
      Selvester score. In conclusion, the ECG estimated MaR was stable between the
      earliest recording time and initiation of reperfusion treatment only in a
      subgroup of the patients with STEMI. The findings of this study may suggest
      heterogeneity in regards to the development of the MaR and could indicate a
      potential need for differentiation in the acute treatment.

PMID- 24878033
TI  - Predictors of survival for younger patients less than 50 years of age with non
      small cell lung cancer (NSCLC): a California Cancer Registry analysis.
AB  - BACKGROUND: Non-small cell lung cancer (NSCLC) is uncommonly diagnosed in
      patients younger than 50 years of age. We analyzed the California Cancer Registry
      (CCR) to describe epidemiologic characteristics and outcomes in this patient
      subset and to identify factors prognostic for cause-specific survival (CSS).
      METHODS: Patients diagnosed with NSCLC between 1/1/98 through 12/31/09 and
      reported to the (CCR) as of October 2011 were included. The primary outcome
      measure was CSS. Cox regression models were used to evaluate predictors of CSS in
      young patients with NSCLC, adjusted for potential confounders. Interaction
      analysis was performed between age groups (<50 vs. >=50) and specific demographic
      and tumor covariates. RESULTS: We identified 132,671 lung cancer cases, of which
      114,451 (86.3%) had NSCLC. Of these, 6389 (5.6%) were<50 years of age (median, 46
      years). The most common histology was adenocarcinoma (3697, 57.9%). Most patients
      had stage III (1522, 23.8%) or IV (3655, 57.2%) disease. Fewer young patients
      were diagnosed in recent years (n, % of total NSCLC population of that era): 1998
      2001 (2355, 6.0), 2002-2005 (2182, 5.7), and 2006-2009 (1852, 5.0), P<0.001.
      Multivariate analysis showed that age <50 years was an independent predictor of
      improved CSS (HR 0.827, P<0.001). Significant predictors of better CSS in
      patients <50 years included female sex, Asian or Hispanic ethnicity, lower stage,
      later year of diagnosis, and higher socioeconomic status, among others.
      Adenocarcinoma histology was not associated with improved CSS in this patient
      subset (HR 0.987, P=0.78). Interaction analysis revealed that Hispanic race and
      bronchioloalveolar histology had differential CSS outcomes dependent on age
      group. CONCLUSIONS: This large registry study found that age <50 years is an
      independent predictor of improved CSS. Variables prognostic for CSS differed
      somewhat from those in older patients.

PMID- 24878034
TI  - Changes in repeated-sprint performance in relation to change in locomotor profile
      in highly-trained young soccer players.
AB  - The aim of this study was to examine the effects of changes in maximal aerobic
      (MAS) and sprinting (MSS) speeds and the anaerobic reserve (ASR) on repeated
      sprint performance. Two hundred and seventy highly-trained soccer players (14.5
      +/- 1.6 year) completed three times per season (over 5 years) a maximal
      incremental running test to approach MAS, a 40-m sprint with 10-m splits to
      assess MSS and a repeated-sprint test (10 * 30-m sprints), where best (RSb) and
      mean (RSm) sprint times, and percentage of speed decrement (%Dec) were
      calculated. ASR was calculated as MSS-MAS. While ?RSb were related to ?MSS and
      ?body mass (r(2) = 0.42, 90%CL[0.34;0.49] for the overall multiple regression, n
      = 334), ?RSm was also correlated with ?MAS and ?sum of 7 skinfolds (r(2) = 0.43
      [0.35;0.50], n = 334). There was a small and positive association between ?%Dec
      and ?MAS (r(2) = 0.02 [-0.07;0.11], n = 334). Substantial ?MSS and ?MAS had a
      predictive value of 70 and 55% for ?RSm, respectively. Finally, ?ASR per se was
      not predictive of ?RSm (Cohen's = +0.8 to -0.3 with increased ASR), but the
      greater magnitude of ?RSm improvement was observed when MSS, MAS and ASR
      increased together (0.8 vs. +0.4 with ASR increased vs. not, additionally to MSS
      and MAS). Low-cost field tests aimed at assessing maximal sprinting and aerobic
      speeds can be used to monitor ?RS performance.

PMID- 24878035
TI  - The effect of age on rat rotator cuff muscle architecture.
AB  - BACKGROUND: Understanding rotator cuff muscle function during disease development
      and after repair is necessary for preventing degeneration and improving
      postsurgical outcomes, respectively. The rat is a commonly used rotator cuff
      animal model; however, unlike humans, rats continue to grow throughout their
      lifespan, so age-related changes in muscle structure may complicate an
      understanding of muscle adaptations to injury. METHODS: Infraspinatus and
      supraspinatus muscle mass, fiber length, pennation angle, sarcomere length, and
      physiological cross-sectional area (PCSA) were measured in Sprague-Dawley rats (n
      = 30) with a body mass ranging from 51 to 814 g (approximately 3 weeks to
      approximately 18 months). RESULTS: Both the supraspinatus and infraspinatus
      showed a striking conservation of sarcomere length throughout growth. There was
      linear growth in muscle mass and PCSA, nonlinear growth in muscle length and
      fiber bundle length, and a linear relationship between humeral head diameter and
      fiber bundle length, suggesting that muscle fiber length (serial sarcomere
      number) adjusted according to skeletal dimensions. These muscle growth
      trajectories allowed sarcomere length to remain nearly constant. DISCUSSION:
      During the typical rat rotator cuff experimental period (animal mass, 400-600 g),
      muscle mass will increase by 30%, fiber length will increase by 7%, and PCSA will
      increase by 27%, but sarcomere lengths are nearly constant. Therefore, these
      normal growth-induced changes in architecture must be considered when muscle
      atrophy or fiber shortening is measured after rotator cuff tears in this model.

PMID- 24878036
TI  - Decreased blood flow in the throwing arm of professional baseball pitchers.
AB  - BACKGROUND: As a consequence of the repetitive forces placed on the throwing arm
      of a baseball player, various bony, capsuloligamentous, and muscular adaptations
      occur and have been identified. However, no research has identified whether
      adaptations also exist in the vasculature of the upper extremity in the
      competitive baseball player. METHODS: Fifty-one professional baseball pitchers
      and 34 position players participated. Diagnostic ultrasound was used to measure
      bilateral blood flow of the brachial artery. These measurements were taken with
      the participant standing with the test arm resting at the participant's side and
      again with the test arm in a provocative shoulder position. RESULTS: The throwing
      arm of the pitchers had significantly less blood flow volume when in the
      provocative shoulder position compared with their nonthrowing arm (P = .01).
      Pitchers did not have any bilateral difference while in the resting position (P =
      .19). There were no bilateral differences among the position players while in the
      resting (P = .64) or provocative positions (P = .63). Pitchers had significantly
      less blood flow of the throwing shoulder while in the provocative position
      compared with position players (P = .02). There were no other between-group
      differences. CONCLUSIONS: While in a provocative shoulder position, pitchers have
      significantly less blood flow in their throwing arm compared with their
      nonthrowing arm and with the throwing arm of position players. These results
      provide a descriptive profile of blood flow volume among baseball players, which
      may be used in the evaluation and treatment of such athletes with vascular
      disorders.

PMID- 24878037
TI  - Delay discounting rates: a strong prognostic indicator of smoking relapse.
AB  - BACKGROUND: Recent evidence suggests that several dimensions of impulsivity and
      locus of control are likely to be significant prognostic indicators of relapse.
      METHOD: One-hundred and thirty-one treatment seeking smokers were enrolled in six
      weeks of multi-component cognitive-behavioral therapy with eight weeks of
      nicotine replacement therapy. ANALYSIS: Cox proportional hazard regressions were
      used to model days to relapse with each of the following: delay discounting of
      $100, delay discounting of $1000, six subscales of the Barratt Impulsiveness
      Scale (BIS), Rotter's Locus of Control (RLOC), Fagerstrom's Test for Nicotine
      Dependence (FTND), and the Perceived Stress Scale (PSS). Hazard ratios for a one
      standard deviation increase were estimated with 95% confidence intervals for each
      explanatory variable. Likelihood ratios were used to examine the level of
      association with days to relapse for different combinations of the explanatory
      variables while accounting for nicotine dependence and stress level. RESULTS:
      These analyses found that the $100 delay discounting rate had the strongest
      association with days to relapse. Further, when discounting rates were combined
      with the FTND and PSS, the associations remained significant. When the other
      measures were combined with the FTND and PSS, their associations with relapse non
      significant. CONCLUSIONS: These findings indicate that delay discounting is
      independently associated with relapse and adds to what is already accounted for
      by nicotine dependence and stress level. They also signify that delay discounting
      is a productive new target for enhancing treatment for tobacco dependence.
      Consequently, adding an intervention designed to decrease discounting rates to a
      comprehensive treatment for tobacco dependence has the potential to decrease
      relapse rates.

PMID- 24878038
TI  - New experimental models of skin homeostasis and diseases.
AB  - Homeostasis, whose regulation at the molecular level is still poorly understood,
      is intimately related to the functions of epidermal stem cells. Five research
      groups have been brought together to work on new in vitro and in vivo skin models
      through the SkinModel-CM program, under the auspices of the Spanish Autonomous
      Community of Madrid. This project aims to analyze the functions of DNA
      methyltransferase 1, endoglin, and podoplanin in epidermal stem cell activity,
      homeostasis, and skin cancer. These new models include 3-dimensional organotypic
      cultures, immunodeficient skin-humanized mice, and genetically modified mice.
      Another aim of the program is to use skin-humanized mice to model dermatoses such
      as Gorlin syndrome and xeroderma pigmentosum in order to optimize new protocols
      for photodynamic therapy. 

PMID- 24878039
TI  - Increasing adiposity is associated with higher adipokine levels and lower bone
      mineral density in obese older adults.
AB  - CONTEXT: Although obesity is associated with high bone mass, recent reports
      suggest an increase in the incidence of fractures in obese patients. OBJECTIVES:
      The objectives of the study were to evaluate the influence of increasing body fat
      on bone mineral density (BMD) and to determine the influence of the different
      adipokines on BMD in frail obese elderly patients. DESIGN AND SETTING: This is a
      cross-sectional study of baseline characteristics of elderly obese patients
      participating in a lifestyle therapy with diet with or without exercise and
      conducted in a university setting. PATIENTS: One hundred seventy-three, elderly
      (>=65 y old), obese (body mass index of >=30 kg/m(2)) who were mostly frail
      participated in the study. OUTCOME MEASURES: BMD, percentage of total body fat,
      percentage of fat-free mass, percentage of lean mass, body mass index,
      adiponectin, leptin, IL-6, bone turnover markers (osteocalcin and C-telopeptide),
      high-sensitivity C-reactive protein, free estradiol, and 25-hydroxyvitamin D were
      measured. RESULTS: Higher tertiles of percentage body fat and lower lean mass
      were associated with a lower BMD. High-sensitivity C-reactive protein levels were
      highest in the highest fat tertile (third, 5.5 +/- 5.4 vs first, 1.5 +/- 1.3
      mg/L, P < .05) for women, whereas IL-6 levels were highest in the highest tertile
      in men (third, 3.5 +/- 3.1 vs first, 1.7 +/- 0.8 pg/mL, P < .05). Leptin
      increased with increasing fat tertiles in both genders (P < .05), whereas
      adiponectin increased with increasing fat tertiles only in men (P < .05). A
      multivariate analysis revealed adiponectin as an important mediator of the effect
      of fat mass on BMD. Osteocalcin levels were highest in the highest fat tertile in
      women but not in men. Physical function test scores decreased with increasing fat
      tertiles in women (P < .05) but not in men. CONCLUSIONS: Increasing adiposity
      together with decreasing lean mass is associated with lower BMD, higher adipokine
      levels, and worsening frailty in elderly obese adults.

PMID- 24878040
TI  - The combination of vitamin D deficiency and mild to moderate chronic kidney
      disease is associated with low bone mineral density and deteriorated femoral
      microarchitecture: results from the KNHANES 2008-2011.
AB  - CONTEXT: Although mild to moderate chronic kidney disease (CKD) and vitamin D
      deficiency are prevalent in the elderly population worldwide and are associated
      with sarcopenia, their influence on bone mineral density (BMD) has not been
      determined. OBJECTIVE: The objective of the study was to determine the combined
      effects of vitamin D deficiency and CKD on BMD in the elderly population and
      their relationships with sarcopenia and PTH levels. DESIGN, SETTING, AND
      SUBJECTS: This was a cross-sectional study with nationally representative samples
      of 6949 subjects aged 55 years or older from the Korea National Health and
      Nutrition Examination Surveys conducted between 2008 and 2011. MAIN OUTCOME
      MEASURES: The study population was divided into four groups according to vitamin
      D and CKD status. The combined association of CKD and vitamin D deficiency
      [25(OH)D<20 ng/mL] with osteopenia or osteoporosis was assessed, and the status
      of PTH and the sarcopenic index (appendicular skeletal muscle mass as a
      percentage of body weight or appendicular skeletal muscle mass per weight) as a
      measure of sarcopenia were evaluated. RESULTS: BMD in the total hip and femoral
      neck as well as femoral bone geometry was markedly deteriorated in stage 3 and 4
      CKD subjects with vitamin D deficiency compared with other groups. Regardless of
      gender, these subjects also had higher levels of PTH and increased prevalence of
      sarcopenia. Multivariable logistic regression analyses demonstrated that CKD
      subjects with vitamin D deficiency showed a significantly increased risk of
      osteoporosis or osteopenia [odds ratios 1.49 and 2.06 (1.81 and 2.65) at the
      femur neck and total hip, respectively, in women (men)], which was mainly
      associated with elevated levels of PTH and sarcopenia in these groups.
      CONCLUSIONS: The combination of mild to moderate CKD and vitamin D deficiency was
      significantly associated with low BMD in a geriatric population, linked with
      hyperparathyroidism and sarcopenia.

PMID- 24878042
TI  - Different pattern of epigenetic changes of the GNAS gene locus in patients with
      pseudohypoparathyroidism type Ic confirm the heterogeneity of underlying
      pathomechanisms in this subgroup of pseudohypoparathyroidism and the demand for a
      new classification of GNAS-related disorders.
AB  - CONTEXT: Disorders characterized by PTH resistance are grouped within the term
      pseudohypoparathyroidism type I (PHPI). Most subtypes of this disease are caused
      by genetic or epigenetic changes of the GNAS locus leading to deficiency of the
      alpha-subunit of stimulatory G proteins (Gsalpha). Because the in vitro measured
      Gsalpha protein activity is normal in pseudohypoparathyroidism Ic (PHPIc), it had
      previously been postulated that this subtype is caused by impairment of distinct
      components of the G protein-signaling pathway. However, recently, pathogenic GNAS
      mutations in a subset of PHPIc patients were found. OBJECTIVE: To clarify the
      underlying pathogenic mechanism of GNAS exon 1-13 mutation-negative PHPIc cases
      by investigating the differentially methylated regions of GNAS for epigenetic
      abnormalities. PATIENTS AND METHODS: The methylation pattern of GNAS exons A/B,
      AS, XL, and NESP from blood-derived leukocytes of 26 PHPIc patients was assessed
      by pyrosequencing of bisulfite-converted DNA. RESULTS: Six patients presented
      with three different patterns of epigenetic changes. One patient had an exclusive
      loss of methylation of exon A/B associated with a STX16 deletion; four patients
      had an additional loss of methylation in XL and AS and a gain of methylation in
      NESP; and one patient presented with partial GNAS methylation changes concerning
      all differentially methylated regions. CONCLUSIONS: Our results confirm that
      PHPIc is a heterogeneous entity caused in part by impaired Gsalpha function, not
      only due to mutations, but also due to abnormal imprinting of GNAS. However, in
      the majority of cases of PHPIc, the underlying etiopathogenesis remains elusive.

PMID- 24878041
TI  - Parent-of-origin effects on glucose homeostasis in polycystic ovary syndrome.
AB  - CONTEXT: Polycystic ovary syndrome (PCOS) is a highly heritable complex trait.
      Parents of affected women have reproductive and metabolic phenotypes. OBJECTIVE:
      We tested the hypothesis that there are parental effects on the heritability of
      fasting dysglycemia in women with PCOS. DESIGN AND SETTING: This was a cross
      sectional study at an academic medical center. PARTICIPANTS: PARTICIPANTS
      included 367 women with PCOS and their parents (1101 total subjects). MAIN
      OUTCOME MEASURES: We compared maternal and paternal contributions to heritability
      of fasting dysglycemia and to transmission of the PCOS susceptibility allele of
      D19S884 within the fibrillin-3 gene (D19S884-A8) on fasting dysglycemia. RESULTS:
      Fathers had higher fasting glucose levels, prevalence of fasting dysglycemia and
      proinsulin to insulin molar ratios (P < .0001), a marker of defective insulin
      processing, compared with mothers. Heritability of fasting dysglycemia was
      significant in PCOS families (h(2) = 37%, SE = 10%, P = .001). Maternal
      heritability (h(2) = 51%, SE = 15%, P = .0009) was higher than paternal
      heritability (h(2) = 23 %, SE = 23%, P = .186) of fasting dysglycemia after
      adjustment for age and body mass index. Within dysglycemic probands, there was
      increased maternal compared with paternal transmission of D19S884-A8 (maternal
      84% vs paternal 45%, chi(2) = 6.51, P = .011). CONCLUSIONS: There was a sex
      difference in the parental metabolic phenotype with fathers having an increased
      risk of fasting dysglycemia and evidence for pancreatic beta-cell dysfunction
      compared with mothers. However, only maternal heritability had significant
      effects on the prevalence of fasting dysglycemia in women with PCOS. Furthermore,
      there were maternal parent-of-origin effects on transmission of D19S884-A8
      probands with fasting dysglycemia. These findings suggest that maternal factors,
      genetic and perhaps epigenetic, contribute to the metabolic phenotype in affected
      women.

PMID- 24878043
TI  - Genome-wide analyses of ChIP-Seq derived FOXA2 DNA occupancy in liver points to
      genetic networks underpinning multiple complex traits.
AB  - BACKGROUND: Forkhead Box A2 (FOXA2) exerts an influence on glucose homeostasis
      via activity in the liver. In addition, a key genome-wide association study
      (GWAS) recently demonstrated that genetic variation, namely rs6048205, at the
      FOXA2 locus is robustly associated with fasting glucose levels. Our hypothesis
      was that this DNA-binding protein regulates the expression of a set of molecular
      pathways critical to endocrine traits. METHODS: Drawing on our laboratory and
      bioinformatic experience with chromatin immunoprecipitation followed by massively
      parallel sequencing, we analyzed our existing FOXA2 chromatin immunoprecipitation
      followed by massively parallel sequencing data generated in human liver, using
      the algorithm hypergeometric optimization of motif enrichment, to gain insight
      into its global genomic binding pattern from a disease perspective. RESULTS: We
      performed a pathway analysis of the gene list using the gene set enrichment
      analysis algorithm, which yielded a number of significant annotations. Motivated
      by the fact that the FOXA2 locus has been implicated by GWAS, we cross-referenced
      the occupancy sites with the National Institutes of Health GWAS catalog and found
      strong evidence for the enrichment of loci implicated in endocrine,
      neuropsychiatric, cardiovascular, and cancer trait categories, but interestingly
      there was no evidence for enrichment for inflammation related traits.
      Intriguingly, a FOXA2 occupancy site coincided with rs6048205, suggesting that
      this variant confers its effect, at least partially, via a perturbation of a
      FOXA2 feedback mechanism. CONCLUSION: Our data strongly suggest that FOXA2 is
      acting as a master regulator of key pathways that are enriched for loci
      implicated by GWAS for most trait categories, with the clear exception of
      inflammation, suggesting that this factor exerts its effect in this context via
      noninflammatory processes.

PMID- 24878044
TI  - Renaissance of (18)F-FDG positron emission tomography in the imaging of
      pheochromocytoma/paraganglioma.

PMID- 24878045
TI  - Subclinical thyroid dysfunction and hip fracture and bone mineral density in
      older adults: the cardiovascular health study.
AB  - BACKGROUND: Subclinical thyroid dysfunction is common in the elderly, yet its
      relationship with hip fracture and bone mineral density (BMD) is unclear.
      OBJECTIVE: We examined the association between endogenous subclinical hyper- and
      hypothyroidism and hip fracture and BMD in older adults. METHODS: A total of 4936
      US individuals 65 years old or older enrolled in the Cardiovascular Health Study
      and not taking thyroid preparations were included. Analyses of incident hip
      fracture were performed by thyroid status, over a median follow-up of 12 years. A
      cross-sectional analysis of thyroid status and BMD was performed in a subset of
      1317 participants who had dual-energy x-ray absorptiometry scans. Models were
      adjusted for risk factors and stratified by sex. RESULTS: No association was
      found between subclinical hypothyroidism and incident hip fracture compared with
      euthyroidism, when assessed at a single time point or persisting at two time
      points, in either women [hazard ratio (HR) 0.91, 95% confidence interval (CI)
      0.69-1.20 for a single and HR 0.79, 95% CI 0.52-1.21 for two time points] or men
      (HR 1.27, 95% CI 0.82-1.95 for a single and HR 1.09, 95% CI 0.57-2.10 for two
      time points). Likewise, no association was found between subclinical
      hyperthyroidism and incident hip fracture in either sex (HR 1.11, 95% CI 0.55
      2.25 in women and HR 1.78, 95% CI 0.56-5.66 in men). No association was found
      between subclinical thyroid dysfunction and BMD at the lumbar spine, total hip,
      or femoral neck sites. CONCLUSIONS: Our data suggest no association between
      subclinical hypothyroidism or subclinical hyperthyroidism and hip fracture risk
      or BMD in older men and women. Additional data are needed to improve the
      precision of estimates for subclinical hyperthyroidism and in men.

PMID- 24878046
TI  - Acute hyperglycemia reduces cerebrovascular reactivity: the role of glycemic
      variability.
AB  - CONTEXT: Cerebral vasomotor reactivity (CVR) is reduced in patients with diabetes
      mellitus (DM), and glucose variability (GV) might be responsible for
      cerebrovascular damage. OBJECTIVE: Studying patients with insulin resistance
      without DM, we explored the role of GV in impairing CVR. PATIENTS: We studied 18
      metabolic syndrome (MS) patients without DM, 9 controls (C), and 26 patients with
      DM. MAIN OUTCOME MEASURES: Groups were compared in terms of CVR, GV, and 24-hour
      blood pressure. To evaluate the impact of acute hyperglycemia on CVR, a
      hyperglycemic clamp was performed in MS patients and controls. RESULTS: Baseline
      CVR was reduced in DM vs C and MS (C vs DM = 20.2, 95% CI = 3.5-36.9, P = .014;
      and MS vs DM = 22.2, 95% CI = 8.6-35.8, P = .001), but similar between MS and C
      (MS vs C = 2.0, 95% CI = -14.7 to 18.7, P = .643). During acute hyperglycemia,
      CVR fell in MS and C to values comparable to DM. GV progressively increased from
      C to MS to DM. In MS, CVR at 120 minutes and GV displayed a negative correlation
      (r = -0.48, P = .043), which did not change after controlling for mean 24-hour
      systolic and diastolic blood pressure. In MS, the CVR reduction was significantly
      correlated to GV (r = 0.55, P = .02). CONCLUSIONS: GV is increased in patients
      with MS but without DM and is the major predictor of CVR reduction induced by
      acute hyperglycemia, possibly representing the earliest cause of cerebrovascular
      damage in DM.

PMID- 24878047
TI  - Influence of vitamin D status on the effect of statins on bone mineral density
      and bone turnover markers in postmenopausal women.
AB  - OBJECTIVE: This study sought to assess whether the association between statin use
      and bone mineral density (BMD) and bone turnover markers is modulated by serum 25
      hydroxyvitamin D (25OHD) levels in postmenopausal women. Design, Participants,
      and Settings: Approximately 1422 postmenopausal women were recruited from the
      Camargo Cohort after excluding those with any known medical disorder or drug that
      might affect bone metabolism. Participants were categorized into four groups:
      25OHD levels of 20 ng/mL or less and not taking statins (group 1; n = 492); 25OHD
      levels greater than 20 ng/mL and on statins (group 2; n = 143); 25OHD levels of
      20 ng/mL or less and using statins (group 3; n = 112); and 2OHD levels greater
      than 20 ng/mL and non-statin use (group 4; n = 675). Multivariate analyses were
      performed to compare BMD and bone turnover markers between groups. RESULTS: Women
      in group 2 had an adjusted femoral neck and total hip BMD higher than women in
      group 1 (P < .0001 and P = .003, respectively). A trend toward a significant
      difference was observed regarding lumbar BMD (P = .08). Serum aminoterminal
      propeptide of type 1 collagen and C-terminal telopeptide of type 1 collagen
      levels were lower in group 2 than in group 1, in crude and adjusted models,
      although only serum C-terminal telopeptide of type 1 collagen difference was
      significant (P = .009). CONCLUSIONS: Women on statins and serum 25OHD levels
      above 20 ng/mL have greater BMD and less bone resorption than those without
      either of the factors. Differences, however, are not significant in women with
      only one of them. Vitamin D and statins seem to interact positively in their
      effects on bone metabolism.

PMID- 24878048
TI  - Reduced GLP-1R expression in gastric glands of patients with type 2 diabetes
      mellitus.
AB  - BACKGROUND: The incretin effect is reduced in type 2 diabetes mellitus (T2DM)
      patients. Whether the impaired function of the enteropancreatic axis in these
      patients is due to defective GLP-1 receptor (GLP-1R) expression in
      extrapancreatic target organs is not known. AIMS AND METHODS: To compare the GLP
      1R expression and distribution in gastric mucosa biopsies of patients with (n
      =22) and without (n =22) T2DM referred for routine esophagogastroduodenoscopies.
      GLP-1R mRNA levels were estimated by real-time PCR. The intensity of GLP-1R
      immunostaining, frequency, and types of glandular cells bearing GLP-1R and their
      glandular distribution in different stomach mucosa regions were evaluated by
      immunohistochemical morphological semiquantitative and quantitative analysis.
      RESULTS: Mean mRNA GLP-1R levels were significantly reduced in patients with T2DM
      compared with nondiabetic patients (P < .02). Immunohistochemical analysis
      revealed that the reduced GLP-1R expression in T2DM patients was due to a
      decreased intensity of immunostaining (P < .01). The number of glandular GLP-1R
      bearing cells in both body and antrum mucosa was decreased in T2DM patients. Most
      notably, the frequency of GLP-1R immunoreactive acid-secreting parietal cells was
      reduced in the neck area of the gastric principal glands of T2DM patients (P <
      .01). No correlation was found between the reduced GLP-1R expression and clinical
      parameters including body mass index, age, glycosylated hemoglobin, and disease
      duration. CONCLUSION: This is the first evidence of reduced GLP-1R expression in
      gastric glands of T2DM patients. These data demonstrate that the defective
      function of the incretin axis in T2DM may also result from decreased GLP-1R
      expression in its extrapancreatic target organs.

PMID- 24878049
TI  - Decreased birth weight, length, and head circumference in children born by women
      years after treatment for hyperthyroidism.
AB  - CONTEXT: Whether hyperthyroidism influences the birth characteristics of children
      born several years after treatment is unknown. OBJECTIVE: The objective of the
      study was to compare birth characteristics in singleton newborns delivered by
      women previously treated for Graves' disease (GD), toxic nodular goiter (TNG), or
      nontoxic goiter (NTG). DESIGN: This was a nested case-control design within a
      national cohort registry study from 1950 through 2006. SETTING: The study was
      conducted at a university and a hospital center in collaboration. PATIENTS: The
      birth characteristics of newborns (n = 3421) delivered in a cohort of 43 633
      women treated for GD or toxic nodular goiter by radioiodine or surgery (exposed
      group) at least 1 year prior to pregnancy were compared with newborns (n = 2914)
      of 45 655 mothers, previously operated for NTG (unexposed group). MAIN OUTCOME:
      The primary outcome was birth weight, length, and head circumference. The
      secondary outcome was malformations, gestational age, and type of
      hyperthyroidism. RESULTS: The birth weight of exposed children was 3431 +/- 607 g
      (mean +/- SD) compared with the unexposed, 3520 +/- 641 g (P < .001). The
      cumulative odds ratio (OR) for lower birth weight was 1.29 [95% confidence
      interval (CI) 1.16-1.43]. The average birth length for the exposed children was
      50.0 +/- 2.7 cm compared with the unexposed of 50.4 cm +/- 2.6 cm (P < .01)
      [cumulative OR 1.25 (95% CI 1.13-1.37)]. The head circumference was 34.5 +/- 1.9
      cm among exposed and 34.7 +/- 1.8 cm, respectively (P < .001), with an OR of 1.24
      (95% CI 1.13-1.35). No differences in birth characteristics were observed between
      children born after maternal GD or toxic nodular goiter. CONCLUSIONS: Previous GD
      or TNG may influence the birth characteristics several years after radioiodine or
      surgical treatment.

PMID- 24878050
TI  - Association between urinary 6-sulfatoxymelatonin excretion and arterial stiffness
      in the general elderly population: the HEIJO-KYO cohort.
AB  - CONTEXT: Melatonin may have a preventive effect on atherosclerosis by regulating
      sleep quality and circadian biological rhythmicity. However, whether endogenous
      melatonin is associated with arterial stiffness, a marker reflecting
      atherosclerosis, is unclear. OBJECTIVE: The objective of the study was to
      determine the association between endogenous melatonin and arterial stiffness.
      DESIGN AND PARTICIPANTS: A total of 641 community-based elderly individuals were
      enrolled in this cross-sectional study (mean age 71.4 y). MEASURES: We measured
      overnight urinary 6-sulfatoxymelatonin excretion (UME) and cardioankle vascular
      index (CAVI) as indices of melatonin secretion and arterial stiffness,
      respectively. RESULTS: The median UME was 6.8 MUg (interquartile range 4.1-10.5)
      and the mean value of CAVI was 9.1 +/- 1.1. High CAVI (ie, >= 9.0) was observed
      in 334 participants (52.1%). Univariate logistic regression models revealed
      marginal to significant associations between high CAVI and age, gender, body mass
      index, hypertension, diabetes, estimated glomerular filtration rate, log
      transformed UME, bedtime, duration in bed, daytime physical activity, and log
      transformed nighttime physical activity. In the multivariate logistic regression
      model, simultaneously adjusted for the former independent variables, higher log
      transformed UME was significantly associated with a lower odds ratio (OR) for
      high CAVI (adjusted OR 0.708; 95% confidence interval 0.536-0.935; P = .015).
      This inverse association between log-transformed UME and high CAVI indicated that
      an increase in log-transformed UME by 1 SD was associated with an 18.1% (95%
      confidence interval 1.4-31.9) decrease in high CAVI prevalence. CONCLUSIONS: UME
      is significantly and inversely associated with arterial stiffness in the general
      elderly population. The association was independent of several major causes of
      atherosclerosis.

PMID- 24878052
TI  - Adrenal function after adrenalectomy for subclinical hypercortisolism and
      Cushing's syndrome: a systematic review of the literature.
AB  - CONTEXT: The postoperative course of patients with subclinical hypercortisolism
      (SH) is yet to be clarified. The aims are to review the prevalence and predictive
      factors of postoperative adrenal insufficiency and the time to recover a normal
      adrenocortical function in patients with SH and Cushing's syndrome (CS). EVIDENCE
      ACQUISITION: Using the PubMed database, we conducted a systematic review of the
      literature, selecting studies published from 1980 to 2013. EVIDENCE SYNTHESIS: Of
      the 1522 papers screened, 28 were selected (13 retrospective, 14 prospective, and
      one randomized controlled trial). The prevalence of postoperative adrenal
      insufficiency was 65.3% in 248 SH subjects and 99.7% in 377 CS patients. Patients
      with SH were reclassified according to the following diagnostic criteria:
      subjects defined by pathological dexamethasone test only (DEX), and those defined
      by the dexamethasone test with one (DEX+1) or two additional criteria (DEX+2);
      and they were compared with CS patients. The prevalence of adrenal insufficiency
      was 51.4, 60.6, 91.3, and 99.7%, respectively, with no significant difference
      between the two latter groups. The test with the best compromise between
      sensitivity (64%) and specificity (81%) in predicting adrenal insufficiency was
      the midnight serum cortisol. The time to achieve eucortisolism was lower in SH
      patients than in CS patients (6.5 vs 11.2 mo; P < .001). CONCLUSIONS: Adrenal
      insufficiency occurs in about half of the patients with SH if defined only by the
      pathological dexamethasone test. However, prevalence of adrenal insufficiency and
      time to recovery are tightly related to the degree of hypercortisolism and
      diagnostic criteria to define SH, which might help to better define SH for future
      studies.

PMID- 24878051
TI  - Decreased adrenomedullary function in infants with classical congenital adrenal
      hyperplasia.
AB  - CONTEXT: Classical congenital adrenal hyperplasia (CAH) due to 21-hydroxylase
      deficiency can cause life-threatening adrenal crises as well as severe
      hypoglycemia, especially in very young children. Studies of CAH patients 4 years
      old or older have found abnormal morphology and function of the adrenal medulla
      and lower levels of epinephrine and glucose in response to stress than in
      controls. However, it is unknown whether such adrenomedullary abnormalities
      develop in utero and/or exist during the clinically high-risk period of infancy
      and early childhood. OBJECTIVE: The objective of the study was to characterize
      adrenomedullary function in infants with CAH by comparing their catecholamine
      levels with controls. Design/Settings: This was a prospective cross-sectional
      study in a pediatric tertiary care center. MAIN OUTCOME MEASURES: Plasma
      epinephrine and norepinephrine levels were measured by HPLC. RESULTS: Infants
      with CAH (n = 9, aged 9.6 +/- 11.4 d) had significantly lower epinephrine levels
      than controls [n = 12, aged 7.2 +/- 3.2 d: median 84 [(25th; 75th) 51; 87] vs
      114.5 (86; 175.8) pg/mL, respectively (P = .02)]. Norepinephrine to epinephrine
      ratios were also significantly higher in CAH patients than controls (P = .01).
      The control infants had primary hypothyroidism, but pre- and posttreatment
      analyses revealed no confounding effects on catecholamine levels. CONCLUSIONS:
      This study demonstrates for the first time that infants with classical CAH due to
      21-hydroxylase deficiency have significantly lower plasma epinephrine levels than
      controls, indicating that impaired adrenomedullary function may occur during
      fetal development and be present from birth. A longitudinal study of
      adrenomedullary function in CAH patients from infancy through early childhood is
      warranted.

PMID- 24878053
TI  - Increases in thyrotropin within the near-normal range are associated with
      increased triiodothyronine but not increased thyroxine in the pediatric age
      group.
AB  - CONTEXT: TSH has been shown in vitro to increase conversion of T4 to T3 and to
      preferentially increase thyroidal T3 secretion. Whether or not these effects are
      significant in vivo, other than in obesity, is unclear. OBJECTIVE: To test
      whether the incremental relationships between free T4 (FT4), free T3 (FT3), and
      TSH are compatible with TSH enhancement of a preferential increase in serum FT3.
      DESIGN AND SETTING: A large database of pediatric and adolescent thyroid test
      results drawn in community clinics from children and adolescents without known
      thyroid disease was analyzed. PATIENTS AND METHODS: RESULTS of FT3, FT4, and TSH
      were studied anonymously. They were crossed with electronic charts to exclude a
      history of positive thyroid autoantibodies and use of thyroid hormone
      preparations, antithyroid medication, or drugs known to affect thyroid function.
      All samples from patients appearing more than once in the database were removed.
      After exclusions, 3276 samples remained. FT4, FT3, and the FT3/FT4 ratios were
      correlated with TSH for the entire group, and the same parameters were segregated
      by TSH quartile. RESULTS were stratified for body mass index and studied
      separately in a normal-weight subgroup. MAIN OUTCOME MEASURES: Stepwise
      correlations of FT4, FT3, and FT3/FT4 ratios with TSH. RESULTS: There was a
      significant positive linear correlation of TSH with FT3 and FT3/FT4 ratios (R =
      0.12; P < .0001 in both), but not with FT4. CONCLUSION: Within the near-euthyroid
      range, increasing TSH levels are associated with increasing FT3 levels, without
      an increase in FT4. This provides in vivo support for TSH enhancing
      preferentially T3 production and/or secretion.

PMID- 24878054
TI  - Relationship between final height and health outcomes in adults with congenital
      adrenal hyperplasia: United Kingdom congenital adrenal hyperplasia adult study
      executive (CaHASE).
AB  - CONTEXT: Treatment of congenital adrenal hyperplasia (CAH) in childhood focuses
      on growth and development and adult final height (FH) is a measure of effective
      treatment. We hypothesized that shorter adults will have more severe underlying
      disease and worse health outcomes. METHODS: This was a cross-sectional analysis
      of 199 adults with CAH. FH and quality of life were expressed as z-scores
      adjusted for midparental target height or UK population height. RESULTS: FH
      correlated inversely with age (men, r = -0.38; women, r = -0.26, P < .01). Men
      and women had z-scores adjusted for midparental target height of -2 and -1,
      respectively, and both groups had UK population height z-scores of -1 below the
      UK population (P < .01). In women, FH was shorter in non-salt-wasting than salt
      wasting classic CAH (P < .05) and in moderately affected genotype group B women
      than either more severely affected groups null and A (P < .01) or the mildest
      group C (P < .001). Short stature and a higher prevalence of hypertension were
      observed in classic CAH patients diagnosed late (after 1 y) compared with those
      diagnosed early and in women treated with glucocorticoid only compared with those
      treated with both glucocorticoids and mineralocorticoids (P < .05). FH did not
      associate with insulin sensitivity, lipid profile, adiposity, or quality of life.
      CONCLUSIONS: Adult CAH patients remain short, although height prognosis has
      improved over time. The shortest adults are those diagnosed late with moderate
      severity CAH and are at increased risk of adult hypertension; we hypothesize that
      these patients are exposed in childhood to high androgens and/or excessive
      glucocorticoids with potential programming of hypertension. Another possibility
      is inadequate mineralocorticoid treatment early in life in the late-diagnosed
      patient group. Prospective studies are now required to examine these hypotheses.

PMID- 24878055
TI  - Diurnal variation in insulin sensitivity of glucose metabolism is associated with
      diurnal variations in whole-body and cellular fatty acid metabolism in
      metabolically normal women.
AB  - CONTEXT: The mechanism(s) responsible for diurnal variations in insulin
      sensitivity of glucose metabolism in healthy people are unclear. OBJECTIVE: The
      objective of the study was to evaluate whether diurnal variations in whole-body
      and cellular fatty acid metabolism could contribute to evening insulin resistance
      in metabolically normal people. SUBJECTS AND DESIGN: We measured plasma the free
      fatty acid (FFA) concentration, palmitate kinetics, and skeletal muscle
      expression of genes involved in fatty acid metabolism at breakfast (7:00 am) and
      dinner (7:00 pm) in 13 overweight (body mass index 27.8 +/- 1.2 kg/m(2)) but
      metabolically normal, women. RESULTS: Plasma FFA concentration was approximately
      30% greater just before consuming dinner than breakfast (P < .05) and remained
      greater after dinner than breakfast (FFA areas under the curve: 0.88 +/- 0.33 and
      0.51 +/- 0.09 MUmol/mL * 4 h, P = .001). However, adipose tissue lipolytic
      activity was not different in the evening and in the morning. Skeletal muscle
      expression of genes that regulate fatty acid oxidation were 38-82% lower, whereas
      genes involved in de novo lipogenesis were 51%-87 % higher before dinner than
      before breakfast (all P < .05), and these changes were associated with diurnal
      variation in the muscle expression of core clock genes that regulate fatty acid
      metabolism. CONCLUSION: Metabolically normal women demonstrate diurnal variations
      in fatty acid metabolism, manifested by an increase in circulating FFAs,
      presumably derived from previous meal consumption rather than lipolysis of
      adipose tissue triglycerides, and a shift in muscle fatty acid metabolism from
      oxidation to lipogenesis. These metabolic alterations could be responsible for
      the known evening decline in insulin sensitivity.

PMID- 24878057
TI  - Von hippel-lindau disease associated pulmonary carcinoid with cranial metastasis.
AB  - CONTEXT: Carcinoids have rarely been described in von Hippel-Lindau (VHL)
      disease. OBJECTIVE: We describe the first reported case of a patient with VHL who
      developed a pulmonary carcinoid that subsequently metastasized to a pre-existent
      cranial hemangioblastoma. RESULTS: Histological and immunohistochemical features
      of the metastatic lesion were similar to the primary carcinoid. Both lesions
      demonstrated heterozygous VHL gene deletions with fluorescence in situ
      hybridization analysis. CONCLUSIONS: This case provides direct molecular genetic
      evidence of an association between VHL and carcinoids.

PMID- 24878056
TI  - Teprotumumab, an IGF-1R blocking monoclonal antibody inhibits TSH and IGF-1
      action in fibrocytes.
AB  - CONTEXT: Thyroid-associated ophthalmopathy (TAO) is the component of Graves'
      disease characterized by orbital inflammation and connective tissue remodeling.
      The IGF-1 receptor (IGF-1R) and TSH receptor (TSHR) form a physical and
      functional complex in orbital fibroblasts. A subset of these fibroblasts is
      derived from infiltrating CD34(+) fibrocytes. Teprotumumab (RV 001, R1507) is a
      human monoclonal anti-IGF-1R blocking antibody currently undergoing a phase 2
      clinical trial in patients with active TAO. OBJECTIVE: To determine whether
      teprotumumab inhibits the induction by TSH of IL-6 and IL-8 in fibrocytes.
      DESIGN: Fibrocytes were treated without or with teprotumumab in combination with
      IGF-1 or TSH. MAIN OUTCOME MEASURES: IL-6 and IL-8 mRNA expression and protein
      production were analyzed by real-time PCR and Luminex, respectively.
      Phosphorylated Akt (S473) levels were analyzed by Western blot. TSHR and IGF-1R
      display was assessed by flow cytometry. RESULTS: Fibrocyte display of IGF-1R and
      TSHR was reduced with teprotumumab, as were IGF-1- and TSH-dependent
      phosphorylated Akt levels. TSH induction of IL-6 and IL-8 mRNA and protein was
      also reduced by the monoclonal antibody. CONCLUSIONS: Teprotumumab attenuates the
      actions of both IGF-1 and TSH in fibrocytes. Specifically, it blocks the
      induction of proinflammatory cytokines by TSH. These results provide, at least in
      part, the molecular rationale for interrogating the therapeutic efficacy of this
      antibody in TAO.

PMID- 24878059
TI  - Flexible binding of PNP pincer ligands to monomeric iron complexes.
AB  - Transition metal complexes supported by pincer ligands have many important
      applications. Here, the syntheses of five-coordinate PNP pincer-supported Fe
      complexes of the type (PNP)FeCl2 (PNP = HN{CH2CH2(PR2)}2, R = iPr ((iPr)PNP), tBu
      ((tBu)PNP), or cyclohexyl ((Cy)PNP)) are reported. In the solid state,
      ((iPr)PNP)FeCl2 was characterized in two different geometries by X-ray
      crystallography. In one form, the (iPr)PNP ligand binds to the Fe center in the
      typical meridional geometry for a pincer ligand, whereas in the other form, the
      (iPr)PNP ligand binds in a facial geometry. The electronic structures and
      geometries of all of the (PNP)FeCl2 complexes were further explored using (57)Fe
      Mossbauer and magnetic circular dichroism spectroscopy. These measurements show
      that in some cases two isomers of the (PNP)FeCl2 complexes are present in
      solution and conclusively demonstrate that binding of the PNP ligand is flexible,
      which may have implications for the reactivity of this important class of
      compounds. 

PMID- 24878058
TI  - Interactions of chromium ions with starch granules in an aqueous environment.
AB  - In this study, interactions of dichromate ions with potato starch granules in
      highly acidic aqueous solutions and at different temperatures were investigated.
      It was found that the process underwent a reduction of Cr(2)O(7)(2-) to Cr(3+)
      accompanied by the formation of intermediate Cr(5+) ions detected by electron
      paramagnetic resonance (EPR) spectroscopy. The reactions took place after the
      attachment of dichromate anions to the granules and resulted in a lowering of the
      Cr(2)O(7)(2-) initial content in the solution. The newly formed Cr(3+) ions were
      both accumulated by the granules or remained in the solution. It was observed for
      the first time that the quantity of such ions taken by the granules from the
      solution was noticeably higher than that delivered by trivalent chromium salt
      solution. It was revealed by scanning electron microscopy coupled with energy
      dispersive X-ray spectroscopy (SEM-EDX) that the chromium ions were not only
      adsorbed on the granule surface but also introduced into the granule interior and
      evenly distributed there. An activation energy of the reduction reaction equal to
      65 kJ.mol(-1) and the optimal parameters of the process were established. The
      proposed mechanism could be useful for the bioremediation of industrial effluents
      polluted by hexavalent chromium compounds.

PMID- 24878060
TI  - [Recurrent syncope in head and neck cancer: a case report].
AB  - The repeated syncopes in case of head and neck cancer are a complication rarely
      described in the literature. They occur when the tumor invade the carotid sinus
      or the afferent fibers of the glossopharyngeal nerve. We report the case of a 62
      year-old man presented episodes of syncope synchronous of a recurrent
      hypopharyngeal tumor scheduled for chemotherapy and gastrostomy. A computerized
      tomography showed a voluminous tumor expanded to the carotid and parapharyngeal
      spaces. After treatment by isporenaline chlorhydrate in intensive care unit, a
      pacemaker was implanted to prevent syncopes and allowed the beginning of the
      chemotherapy. 

PMID- 24878062
TI  - Interferon beta-1a for multiple sclerosis: old drug, new clothes.

PMID- 24878061
TI  - Specific inhibition of p97/VCP ATPase and kinetic analysis demonstrate
      interaction between D1 and D2 ATPase domains.
AB  - The p97 AAA (ATPase associated with diverse cellular activities), also called VCP
      (valosin-containing protein), is an important therapeutic target for cancer and
      neurodegenerative diseases. p97 forms a hexamer composed of two AAA domains (D1
      and D2) that form two stacked rings and an N-terminal domain that binds numerous
      cofactor proteins. The interplay between the three domains in p97 is complex, and
      a deeper biochemical understanding is needed in order to design selective p97
      inhibitors as therapeutic agents. It is clear that the D2 ATPase domain
      hydrolyzes ATP in vitro, but whether D1 contributes to ATPase activity is
      controversial. Here, we use Walker A and B mutants to demonstrate that D1 is
      capable of hydrolyzing ATP and show for the first time that nucleotide binding in
      the D2 domain increases the catalytic efficiency (kcat/Km) of D1 ATP hydrolysis
      280-fold, by increasing kcat 7-fold and decreasing Km about 40-fold. We further
      show that an ND1 construct lacking D2 but including the linker between D1 and D2
      is catalytically active, resolving a conflict in the literature. Applying
      enzymatic observations to small-molecule inhibitors, we show that four p97
      inhibitors (DBeQ, ML240, ML241, and NMS-873) have differential responses to
      Walker A and B mutations, to disease-causing IBMPFD mutations, and to the
      presence of the N domain binding cofactor protein p47. These differential effects
      provide the first evidence that p97 cofactors and disease mutations can alter p97
      inhibitor potency and suggest the possibility of developing context-dependent
      inhibitors of p97. 

PMID- 24878063
TI  - Therapeutic drug monitoring in cancer--are we missing a trick?
AB  - Therapeutic drug monitoring (TDM) can be defined as the measurement of drug in
      biological samples to individualise treatment by adapting drug dose to improve
      efficacy and/or reduce toxicity. The cytotoxic drugs are characterised by steep
      dose-response relationships and narrow therapeutic windows. Inter-individual
      pharmacokinetic (PK) variability is often substantial. There are, however, a
      multitude of reasons why TDM has never been fully implemented in daily oncology
      practice. These include difficulties in establishing appropriate concentration
      target, common use of combination chemotherapies and the paucity of published
      data from pharmacological trials. The situation is different with targeted
      therapies. The large interindividual PK variability is influenced by the
      pharmacogenetic background of the patient (e.g. cytochrome P450 and ABC
      transporters polymorphisms), patient characteristics such as adherence to
      treatment and environmental factors (drug-drug interactions). Retrospective
      studies have shown that targeted drug exposure correlates with treatment response
      in various cancers. Evidence for imatinib currently exists, others are emerging
      for compounds including nilotinib, dasatinib, erlotinib, sunitinib, sorafenib and
      mammalian target of rapamycin (mTOR) inhibitors. Applications for TDM during oral
      targeted therapies may best be reserved for particular situations including lack
      of therapeutic response, severe or unexpected toxicities, anticipated drug-drug
      interactions and concerns over adherence treatment. There are still few data with
      monoclonal antibodies (mAbs) in favour of TDM approaches, even if data showed
      encouraging results with rituximab and cetuximab. TDM of mAbs is not yet
      supported by scientific evidence. Considerable effort should be made for targeted
      therapies to better define concentration-effect relationships and to perform
      comparative randomised trials of classic dosing versus pharmacokinetically-guided
      adaptive dosing. 

PMID- 24878064
TI  - Response to: 'Letter to the editor, European Journal of Cancer', commenting on
      'Performance of formulae based estimates of glomerular filtration rate for
      carboplatin dosing in stage 1 seminoma'.

PMID- 24878065
TI  - Blood 25-hydroxyvitamin D levels and overall mortality in patients with
      colorectal cancer: a dose-response meta-analysis.

PMID- 24878066
TI  - Initial validation of the Death and Dying Distress Scale for the assessment of
      death anxiety in patients with advanced cancer.
AB  - CONTEXT: The experience of death anxiety in patients with advanced cancer has
      been understudied partly because of the lack of a tailored measure for this
      population. The Death and Dying Distress Scale (DADDS) was constructed to address
      this gap. Although an initial version of this instrument has shown promising
      psychometric properties, validation of the finalized version is needed.
      OBJECTIVES: This study aims to validate the recent 15-item DADDS by examining its
      factor structure and construct validity. METHODS: Sixty participants with
      advanced or metastatic cancer were recruited from the Princess Margaret Cancer
      Centre, University Health Network, Toronto, Canada, into a pilot trial of a
      psychological intervention. This article analyzes the baseline measures on death
      anxiety, depressive symptoms (Patient Health Questionnaire-9, Structured Clinical
      Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth
      Edition, Text Revision, Axis 1 Disorders), generalized anxiety (Generalized
      Anxiety Disorder-7), and preparation for end of life (Quality of Life at the End
      of Life-Cancer Scale). Exploratory factor analysis was conducted. Construct
      validity was assessed by correlations between measures. RESULTS: Factor analysis
      revealed a dominant single factor explaining more than 75% of the shared
      variation between items. Factor loadings were high, ranging from 0.57 to 0.86.
      Item communalities were evenly ranged from 0.33 to 0.75 and with the 15:1
      variable to factor ratio, suggest the viability of parameter estimates despite
      the small sample size. Cronbach's alpha was 0.95. Death anxiety was associated
      with less preparation for end of life (r = -0.68, P < 0.0001), more generalized
      anxiety (r = 0.63, P < 0.0001), and more depressive symptom severity (r = 0.50, P
      < 0.0001). Individuals with major depression had greater death anxiety than the
      nondepressed (mean difference = 17; 95% CI = 1.5-33), as did individuals with
      minor depression (mean difference = 25; 95% CI = 10-41). CONCLUSION: The DADDS is
      a valid measure of death anxiety in patients with advanced cancer. It may provide
      useful information in the assessment and treatment of distress in patients near
      the end of life.

PMID- 24878068
TI  - Psychometric properties of the Functional Assessment of Chronic Illness Therapy
      Fatigue (FACIT-Fatigue) in Chinese patients receiving maintenance dialysis.
AB  - CONTEXT: Fatigue is a common symptom reported by patients with end-stage renal
      disease, and it can significantly decrease patients' quality of life. A brief and
      convenient fatigue assessment tool is needed for Chinese patients on maintenance
      dialysis. OBJECTIVES: To determine the psychometric characteristics of the
      Chinese version of the Functional Assessment of Chronic Illness Therapy-Fatigue
      (FACIT-Fatigue) in patients receiving maintenance dialysis. METHODS: The Chinese
      version of the FACIT-Fatigue was obtained from the FACIT system. Test-retest
      reliability of this scale was examined using intraclass correlation coefficients,
      and the internal consistency was calculated by Cronbach's alpha. Content validity
      was examined using the content validity index (CVI), scale-level CVI/universal
      agreement, and scale-level CVI/average agreement. Construct validity was tested
      using Pearson product-moment correlations of the FACIT-Fatigue scores with the
      Revised Piper Fatigue Scale, Hospital Anxiety and Depression Scale, Pittsburgh
      Sleep Quality Index, and disease characteristics during the same period. RESULTS:
      A total of 172 patients (111 males and 61 females, mean age 52.6 +/- 12.5 years)
      completed this study, with a median FACIT-Fatigue score of 41 (first and third
      quartiles 34.3-46). The Chinese version of the FACIT-Fatigue had excellent test
      retest reliability (intraclass correlation coefficient = 0.98) and internal
      consistency (Cronbach's alpha = 0.92); the validity of the scale was supported by
      CVI, scale-level CVI/universal agreement, and scale-level CVI/average agreement
      values of at 0.67-1, 0.85, and 0.96, respectively. The standard error of
      measurement of the FACIT-Fatigue was 1.2. The significant correlations between
      the FACIT-Fatigue score and the Revised Piper Fatigue Scale (r = -0.658),
      Hospital Anxiety and Depression Scale (-0.566), and Pittsburgh Sleep Quality
      Index (-0.489) were supported by the FACIT-Fatigue, with good construct validity
      (all P < 0.01). CONCLUSION: The FACIT-Fatigue had acceptable validity and
      reliability for maintenance dialysis patients and can be used as a valid tool for
      the measurement of fatigue among these Chinese patients.

PMID- 24878067
TI  - Measuring the quality of dying and death in the pediatric intensive care setting:
      the clinician PICU-QODD.
AB  - CONTEXT: In the pediatric intensive care setting, an accurate measure of the
      dying and death experience holds promise for illuminating how critical care
      nurses, physicians, and allied psychosocial staff can better manage end-of-life
      care for the benefit of children and their families, as well as the caregivers.
      OBJECTIVES: The aim was to assess the reliability and validity of a clinician
      measure of the quality of dying and death (Pediatric Intensive Care Unit-Quality
      of Dying and Death 20 [PICU-QODD-20]) in the pediatric intensive care setting.
      METHODS: In a retrospective cohort study, five types of clinicians (primary
      nurse, bedside nurse, attending physician, and the psychosocial clinician and
      critical care fellow most involved in the case) were asked to complete a survey
      for each of the 94 children who died over a 12 month period in the pediatric
      intensive care units of two children's hospitals in the northeast U.S. Analyses
      were conducted within type of clinician. RESULTS: In total, 300 surveys were
      completed by 159 clinicians. Standard item analyses and substantive review led to
      the selection of 20 items for inclusion in the PICU-QODD-20. Cronbach alpha for
      the PICU-QODD-20 ranged from 0.891 for bedside nurses to 0.959 for attending
      physicians. For each type of clinician, the PICU-QODD-20 was significantly
      correlated with the quality of end-of-life care and with meeting the family's
      needs. In addition, when patient/family or team barriers were encountered, the
      PICU-QODD-20 score tended to be significantly lower than for cases in which the
      barrier was not encountered. CONCLUSION: The PICU-QODD-20 shows promise as a
      valid and reliable measure of the quality of dying and death in pediatric
      intensive care.

PMID- 24878069
TI  - Identification of flea species using MALDI-TOF/MS.
AB  - In the present study, a molecular proteomics (MALDI-TOF/MS) approach was used as
      a tool for identifying flea vectors. We measured the MS spectra from 38 flea
      specimens of 5 species including Ctenocephalides felis, Ctenocephalides canis,
      Archaeopsylla erinacei, Xenopsylla cheopis and Stenoponia tripectinata. A blind
      test performed with 24 specimens from species included in a library spectral
      database confirmed that MALDI-TOF/MS is an effective tool for discriminating flea
      species. Although fresh and 70% ethanol-conserved samples subjected to MALDI
      TOF/MS in blind tests were correctly classified, only MS spectra of quality from
      fresh specimens were sufficient for accurate and significant identification. A
      cluster analysis highlighted that the MALDI Biotyper can be used for studying the
      phylogeny of fleas. 

PMID- 24878070
TI  - Characterization of adaptive immune responses induced by a new genetically
      inactivated Salmonella Enteritidis vaccine.
AB  - The superior conservation of antigenic determinants on the surface of genetically
      inactivated bacterial ghosts makes them attractive immunogenic inactivated
      vaccine candidates. The efficacy of Salmonella Enteritidis (SE) ghost vaccination
      was evaluated in chickens by characterizing the nature of the adaptive immune
      response. Chickens from the immunized group demonstrated significant increases in
      SE-specific plasma IgG, intestinal secretory IgA, and lymphocyte proliferative
      response. The populations of CD4, CD8, and TCR gammadelta T-cells in immunized
      chickens were significantly greater than in the controls. Increased levels of IFN
      gamma, IL-2, IL-6 and IL-10 were observed in peripheral blood mononuclear cells
      stimulated with SE specific antigen. After virulent SE challenge, the immune
      system of immunized chickens was rapidly stimulated, as indicated by
      significantly increased population of CD4 and CD8 T-cells. Furthermore, the
      immunized group exhibited decreased challenge strain recovery of the internal
      organs compared to the non-immunized group. Together, these data indicate that
      the immunization induced humoral and cell-mediated immunity might be responsible
      for significant reduction of the virulent challenge strain load in the internal
      organs of immunized chickens. 

PMID- 24877930
TI  - Measurement of inclusive W and Z boson production cross sections in pp collisions
      at sqrt[s] = 8 TeV.
AB  - A measurement of total and fiducial inclusive W and Z boson production cross
      sections in pp collisions at sqrt[s] = 8 TeV is presented. Electron and muon
      final states are analyzed in a data sample collected with the CMS detector
      corresponding to an integrated luminosity of 18.2 +/- 0.5 pb(-1). The measured
      total inclusive cross sections times branching fractions are sigma(pp -> WX)*B(W 
      > lnu) = 12.21 +/- 0.03(stat) +/- 0.24(syst) +/- 0.32(lum) nb and sigma(pp -> ZX)
      * B(Z -> l+l-) = 1.15 +/- 0.01(stat) +/- 0.02(syst) +/- 0.03(lum) nb for the
      dilepton mass in the range of 60-120 GeV. The measured values agree with next-to
      next-to-leading-order QCD cross section calculations. Ratios of cross sections
      are reported with a precision of 2%. This is the first measurement of inclusive W
      and Z boson production in proton-proton collisions at sqrt[s] = 8 TeV.

PMID- 24878071
TI  - Functional interplay between Parkin and Drp1 in mitochondrial fission and
      clearance.
AB  - Autosomal recessive early-onset Parkinson's disease is most often caused by
      mutations in the genes encoding the cytosolic E3 ubiquitin ligase Parkin and the
      mitochondrial serine/threonine kinase PINK1. Studies in Drosophila models and
      mammalian cells have demonstrated that these proteins regulate various aspects of
      mitochondrial physiology, including organelle transport, dynamics and turnover.
      How PINK1 and Parkin orchestrate these processes, and whether they always do so
      within a common pathway remain to be clarified. We have revisited the role of
      PINK1 and Parkin in mitochondrial dynamics, and explored its relation to the
      mitochondrial clearance program controlled by these proteins. We show that PINK1
      and Parkin promote Drp1-dependent mitochondrial fission by mechanisms that are at
      least in part independent. Parkin-mediated mitochondrial fragmentation was
      abolished by treatments interfering with the calcium/calmodulin/calcineurin
      signaling pathway, suggesting that it requires dephosphorylation of serine 637 of
      Drp1. Parkinson's disease-causing mutations with differential impact on
      mitochondrial morphology and organelle degradation demonstrated that the pro
      fission effect of Parkin is not required for efficient mitochondrial clearance.
      In contrast, the use of Forster energy transfer imaging microscopy revealed that
      Drp1 and Parkin are co-recruited to mitochondria in proximity of PINK1 following
      mitochondrial depolarization, indicating spatial coordination between these
      events in mitochondrial degradation. Our results also hint at a major role of the
      outer mitochondrial adaptor MiD51 in Drp1 recruitment and Parkin-dependent
      mitophagy. Altogether, our observations provide new insight into the mechanisms
      underlying the regulation of mitochondrial dynamics by Parkin and its relation to
      the mitochondrial clearance program mediated by the PINK1/Parkin pathway. 

PMID- 24878073
TI  - Being part of an unfolding story: togetherness in everyday occupations when
      ageing.
AB  - AIM: The aim of this study was to explore and enhance the understanding of how
      togetherness in everyday occupations is experienced and discussed among older
      adults. METHOD: Focus-group discussions generated the data and a total of 12
      participants, including six women and six men, divided into three groups,
      participated in this study. Analysis was performed using a grounded theory
      approach. RESULTS: The findings reflect how togetherness in everyday occupations
      can be comprehended as multifold transactional processes, emphasizing how an
      acted belonging was a situated experience connecting people and places through
      unfolding stories. The findings suggest that the process of meaning-making in
      ongoing life was closely associated with togetherness and was negotiated with
      others through shared culture and experiences. Togetherness meant being part of
      something in which the persons involved were contributing to each other in
      various ways. However, being part of togetherness was complicated, especially
      when the person's life situation was challenged in some way. CONCLUSIONS: It was
      apparent from the analysis that togetherness could not be taken for granted.
      Rather, the findings reflect how togetherness was created and maintained through
      an ongoing process of nurturing established relationships as well as creating
      something new around occupations with others.

PMID- 24878072
TI  - Receptor-ligand interaction at 5-HT3 serotonin receptors: a cluster approach.
AB  - A fundamental understanding of the interaction of ligands with biological
      receptors is important because many drugs exert their influence via receptors.
      Using a cluster approach, we have studied the role of structural and electronic
      parameters on receptor-ligand binding by carrying out density functional theory
      based calculations. As model systems, we have studied substituted arylguanidines,
      which activate 5-HT3 receptors in a manner similar to that of serotonin. The
      geometries of the arylguanidine derivatives were fully optimized to obtain the
      lowest energy structures. Electronic properties such as binding energies, dipole
      moments, polarizabilities, and electron affinities, as well as geometric
      properties, such as molecular volume and dihedral angles were calculated, and
      their relationship with binding affinity was evaluated. Results obtained were
      compared to experimental ligand-receptor binding affinity data available. These
      fundamental studies show that though both electronic and geometric properties of
      the ligands are important for binding, the electron affinities of the substituent
      species play a dominant role. Potential new fundamental indices for ligand
      receptor affinity are also discussed. 

PMID- 24878074
TI  - Upper thoracic intradural-extramedullary cavernous malformation presenting as
      subarachnoid hemorrhage without spinal dysfunction: a case report and review of
      the literature.
AB  - A 45-year-old man had subarachnoid hemorrhage (SAH) which was confirmed by lumbar
      puncture, since it was negative on head computed tomography. The result of
      neurological examination was normal. Following pan-cerebral angiography and
      cranial magnetic resonance imaging (MRI) failed to find out the cause of
      bleeding. The whole spinal MRI revealed an intradural-extramedullary mass lesion
      at the upper thoracic level which was consistent with cavernous malformation
      after surgery. When patients presented with SAH of no spinal symptoms, the
      diagnosis of an intradural-extramedullary cavernous malformation is challenging.
      A whole spinal workup should be considered in a patient with spontaneous SAH when
      bleeding from intracranial origin is carefully excluded.

PMID- 24878076
TI  - Correction to Synthesis and Structure Activity Relationship of
      Tetrahydroisoquinoline-Based Potentiators of GluN2C and GluN2D Containing N
      Methyl-d-aspartate Receptors.

PMID- 24878078
TI  - [Comments with regards to scientific research in IMSS].

PMID- 24878079
TI  - [Other notes on research in IMSS].

PMID- 24878077
TI  - [Stem cells biobanks for cell therapy. A reality in Mexico].
AB  - The storage and acquisition of human tissue samples have always been present in
      medicine for centuries; however, biobanks activity has only recently appeared as
      such. The aim of this review is to give a global perspective of the positioning
      of biobanks, particularly an overview of what happens in Mexico. One of the main
      challenges of our country is to establish concerted actions, in wich biobank
      networks will be developed and have the opportunity to share and create new
      science, and to build bridges to facilitate improved practices and
      standardization of biobanks. 

PMID- 24878080
TI  - [Biographical sketch of doctor Emilio Garcia Procel].

PMID- 24878075
TI  - Insights into the human glycan receptor conformation of 1918 pandemic
      hemagglutinin-glycan complexes derived from nuclear magnetic resonance and
      molecular dynamics studies.
AB  - The glycan receptor binding and specificity of influenza A viral hemagglutinin
      (HA) are critical for virus infection and transmission in humans. However,
      ambiguities in the interpretation of the receptor binding specificity of
      hemagglutinin from human- and avian-adapted viruses have prevented an
      understanding of its relationship with aerosol transmissibility, an exclusive
      property of human-adapted viruses. A previous conformational study, which we
      performed, indicated that human and avian receptors sample distinct conformations
      in solution. On the basis of detailed nuclear magnetic resonance (NMR) studies
      provided herein, we offer evidence of the distinct structural constraints imposed
      by hemagglutinin receptor binding sites on the glycan conformational space upon
      binding. The hemagglutinin from the SC18 virus, which has efficient aerosol
      transmissibility in humans (human-adapted), imposed the most stringent
      constraints on the conformational space of the human glycan receptor (LSTc),
      compared to single (NY18) or double (AV18) amino acid HA mutants, a property
      correlating to the ligand-HA binding strength. This relationship was also
      observed for the avian-adapted HA, where the high affinity binding partner, AV18,
      imposed the most stringent conformational constraints on the avian receptor,
      compared to those imposed by NY18. In particular, it is interesting to observe
      how different HAs when binding to human or avian glycosidic receptors impose
      significantly different conformational states, in terms of the states sampled by
      the glycosidic backbone and/or the entire molecule shape (linear or bent), when
      compared to the corresponding unbound glycans. Significantly, we delineate a
      "characteristic NMR signature" for the human adapted hemagglutinin (SC18) binding
      to human glycan receptors. Therefore, the conformational space constraints
      imposed by the hemagglutinin receptor binding site provide a characteristic
      signature that could be a useful tool for the surveillance of human adaptation of
      other (such as H7N9 and H5N1) deadly influenza viruses. 

PMID- 24878081
TI  - [Survival in acute renal failure with conventional therapy or continuous
      replacement therapy].
AB  - OBJECTIVE: To know the survival rate in patients with RIFLE I and II stages on
      acute renal failure, treated with supportive care or continuous renal replacement
      therapy with PRISMA machine, at an intensive care unit. METHODS: There were
      included patients of both sexes, aged 16 to 69 years, with acute renal failure in
      RIFLE I and II stages and score of scale APACHE II lower than 36 points. The
      sample studied was divided in two groups: a group was treated with supportive
      care, and the other group received continuous renal replacement therapy via
      PRISMA machine. We compared mortality between both groups and the association
      with the RIFLE stages with Pearson's chi-squared test. RESULTS: The average score
      of the scale APACHE I was 14 points, and the probability of death was 15 %. The
      patients with acute renal failure RIFLE I were 54.5 % and RIFLE II 45.5 %, with
      mortality of 30.4 % and 38.8 %, respectively. Patients in RIFLE I stage who
      received supportive care and continuous replacement therapy had non-statistical
      differences in mortality (p = 0.356). The mortality in patients with acute renal
      failure in RIFLE II stage treated with continuous replacement therapy was higher
      (p = 0.000). CONCLUSIONS: Because of its accessibility and lower mortality,
      supportive care should be the initial procedure in patients with acute renal
      failure in RIFLE I and II stages.

PMID- 24878082
TI  - [Isolated bacteria from nasal cultures. Are they important in patients with acute
      leukemia?].
AB  - BACKGROUND: The nasal colonization by Staphylococcal (epidermidis or aureus) is
      frequent and it has importance when it is associated to bacteremia in
      immunocompromised patients. The objective was to determine the frequency of
      strains that colonize the nasal mucosa in patients with leukemia and its
      relationship with peripheral blood cultures. METHODS: A retrospective,
      observational, transversal, retrolective study was done. We analyzed the weekly
      results of nasal cultures and peripheral blood cultures in patients with leukemia
      undergoing chemotherapy. The chi-squared test and odds ratio value were estimated
      in the statistical analysis. RESULTS: We included 67 patients, 55 of them with
      acute lymphocytic leukemia (ALL); 28.5 % of the cultures (n = 47) corresponded to
      a positive nasal culture. Staphylococcus epidermidis and Staphylococcus aureus
      were the most isolated bacteria. During the first week of treatment, the positive
      cultures were the most frequently. All the samples isolated were sensitive to
      vancomycin or linezolid. It was established only the association between negative
      nasal cultures and negative peripheral blood cultures (p = 0.0005). Odds ratio
      for positive nasal cultures and the risk of bacteremia was 0.0269. CONCLUSIONS:
      The frequency of the positive bacteria culture was low, with an adequate
      sensitivity measure. The presence of bacteria in nasal culture was not identified
      as a risk factor for the occurrence of bacteremia.

PMID- 24878083
TI  - [Molecular response with triple therapy in patients with chronic myeloid
      leukemia].
AB  - BACKGROUND: Chronic myeloid leukemia is a myeloproliferative disorder which
      results from the translocation t(9;22)(q34;q11). Imatinib mesylate is an
      inhibitor of kinase tyrosine that has proved to be useful in patients with
      chronic myeloid leukemia. Our aim was to evaluate the major molecular response to
      12 months with triple therapy, analyze the evolution of these patients, and the
      hematological and non-hematological toxicity. METHODS: It was performed a
      longitudinal study in patients with diagnosis of chronic myeloid leukemia who
      were treated with sequential triple therapy: Pegylated interferon alpha 2a (90
      MUg/week for four weeks) + imatinib (800 mg a day for 30 days) + cytarabine (20
      mg/m2 from day 1 to 10). Molecular and hematologic responses at 12 months of
      treatment were analyzed. RESULTS: Thirty eight patients with chronic myeloid
      leukemia were eligible; the mean age was 43.4 years and the medians of hemoglobin
      levels, leukocyte and platelet counts at diagnosis were 10 g/dL (5.1 to 16.0
      g/dL), 208 000/MUL3 (10 600 to 529 000/MUL3) and 573 500/MUL3 (130 000 to 4 272
      000/MUL3), respectively. According to the Sokal score, 68.4 % had low risk, 26.3
      % intermediate and 5.3 % high risk. CONCLUSIONS: The hematologic response was
      similar to that reported in the IRIS study, but the molecular response was
      greater in more cases. The adverse hematological effects grades 3-4 and non
      hematological were significative: 45 % and 87 %, which forces to continous
      monitoring. The combination of interferon alpha 2a, cytarabine and a high-dose of
      imatinib induced the major molecular response, of 68.4 %, at 12 months.

PMID- 24878084
TI  - [Response to treatment with tyrosine kinase inhibitors in chronic myeloid
      leukemia].
AB  - BACKGROUND: Chronic myeloid leukemia represents 15 % of all the leukemias in
      adults. With the introduction of tyrosine kinase inhibitors, overall survival at
      10 years is 80-90 %. The objective was to describe the epidemiology, complete
      cytogenetic response and major molecular response with tyrosine kinase inhibitors
      in patients with chronic myeloid leukemia. METHODS: It was performed a
      descriptive cross-sectional study of patients with chronic myeloid leukemia and
      Philadelphia chromosome-positive in treatment with tyrosine kinase inhibitors.
      RESULTS: The sample included 54 patients with a mean age of 41 years; 78 % of
      patients were in chronic phase, and in 8 % of patients were identified complex
      karyotype at diagnosis. All patients received imatinib as first-line treatment.
      We identified mutations in 8 %. The patients with primary or secondary resistance
      (30%) received second-generation tyrosine kinase inhibitors as a second-line
      therapy. Of 35 patients treated with imatinib, 23 had complete cytogenetic
      response, 23 had major molecular response, and 16 had loss of response to
      treatment. Of nine patients treated with nilotinib, two presented complete
      cytogenetic response, two major molecular response, and five loss of response to
      treatment. Of seven patients treated with dasatinib, two had complete cytogenetic
      response, two major molecular response, and four loss of response to treatment.
      CONCLUSIONS: Of patients studied, 30 % was resistant to imatinib, 52 % achieved a
      complete cytogenetic response, and 42 % major molecular response. The use of
      second generation tyrosine kinase inhibitors led to obtain a complete cytogenetic
      and major molecular response in fewer time.

PMID- 24878085
TI  - [Effect of metformin addition to an acute lymphoblastic leukemia chemotherapy
      treatment].
AB  - BACKGROUND: Recently it has been reported a benefit effect with the use of
      metformin in patients with malignant disease. Our objective was to evaluate the
      effect of adding metformin to chemotherapy regimen over the percentage of early
      relapse in acute lymphoblastic leukemia. METHODS: A prospective, longitudinal and
      experimental study was performed in patients with de novo acute lymphoblastic
      leukemia enrolled in the Hospital General de Mexico. They were divided in two
      groups: first group received chemotherapy + metformin (850 mg three times a day);
      second group only received standard chemotherapy. The sample was randomized 3:1
      in favor of the second group. RESULTS: 93 patients were included (73 treated with
      chemotherapy + metformin and 20 received standard chemotherapy), with 303 +/- 53
      days of follow-up. Complete remission was higher in the group without metformin
      (81.3 % [n = 61] versus 70 % [n = 14]), which also presented more patients with
      relapse (47.9 % versus 25 %). Overall survival at one year was of 68 % and free
      survival disease was 64 %, without significant differences between groups.
      Absence of metformin was the only variable of adverse prognostic considered
      significant (p = 0.55). Cox regression showed that adding metfomin reduced 56 %
      the risk of relapse. CONCLUSIONS: The adding metformin to the treatment of
      leukemias showed that was useful in our research. However, randomized and double
      blind studies must be designed in order to express final recommendations about
      its use.

PMID- 24878086
TI  - [Survival of patients with diffuse large B-cell lymphoma].
AB  - BACKGROUND: The overall survival and relapse-free survival have increased with
      current chemotherapy in patients with non-lymphoma Hodgkin. A useful tool to
      evaluate projections is the International Prognostic Index. Our aim was to
      evaluate the relation between the prognosis established with the International
      Prognostic Index and the survival obtained in two years by patients with diffuse
      large B-cell lymphoma. METHODS: An observational, longitudinal, prospective study
      was carried out. Patients included were those with diagnosis and treated along a
      year, who, at some point in their evolution, required hospitalization. All the
      patients received ciclofosfamide, doxorrubicine, vincristine and prednisone;
      additionally, some of them received rituximab. The follow-up average was 26
      months. Survival was estimated with Kaplan-Meier curves. RESULTS: Forty-nine
      patients were included and classified according to the International Prognostic
      Index risk. The survival was 90 % for patients with International Prognostic
      Index low risk, 66.7 % for the patients with intermediate-low risk, 80 % for
      patients with intermediate-high risk, and 81 % for patients with high risk. The
      survival for all risk groups was 77.6 %. When we compared the survival of
      patients with the expected prognosis through the International Prognostic Index,
      we obtained p = 0.0000. CONCLUSIONS: Two years after diagnosis, the survival of
      patients with diffuse large B-cell lymphoma in the study was better than the
      prognosis estimated through the International Prognostic Index, and similar to
      that reported in American studies.

PMID- 24878087
TI  - [Skin cancer incidence in Zacatecas].
AB  - BACKGROUND: Skin cancer is the most frequent cancer related to ultraviolet
      radiation. The aim was to estimate the incidence of skin cancer type, melanoma
      and non-melanoma in Zacatecas, Mexico. METHODS: An epidemiological study was
      carried out during the period from 2008 to 2012. The data were obtained from the
      Instituto Mexicano del Seguro Social (IMSS), Instituto de Seguridad y Servicios
      Sociales de los Trabajadores del Estado (ISSSTE), Secretaria de Salud de
      Zacatecas (SSZ) and a private source, the Centro Medico Alameda. The incidence
      and the global prevalence were estimated. RESULTS: We studied 958 skin cancer
      cases, histopathologically confirmed. The cases were distributed as: 63.6 % basal
      cell carcinomas, 25.8 % squamous cell carcinomas, and 10.6 % melanoma.
      Significantly higher proportions were observed in women in the basal cell
      carcinomas (60.4 %) and squamous cell carcinomas (53.4 %). However, in the case
      of melanoma, the major proportion was observed in men (55.9 %). The more frequent
      skin cancer location was the face and for basal cell carcinoma was the nose (53
      %); for squamous cell carcinomas were the lips (36 %), and for melanoma it was
      also the nose (40 %). The skin cancer incidence was estimated in 20 cases for
      each 100 000 inhabitants. Linear regression analysis showed that the skin cancer
      is increasing at an annual rate of 10.5 %. CONCLUSIONS: The anatomical location
      indicates that solar UV radiation is a risk factor, since the face is the zone
      with major exposure to solar radiation.

PMID- 24878088
TI  - [Clinical conditions at hospitalization and its relation with admission to
      pediatric intensive care unit].
AB  - BACKGROUND: The admission to a pediatric intensive care unit (PICU) depends on
      several factors, but the chances of recovery of the patient are the main cause.
      Most of the patients are admitted from urgency or surgery room, and a minority
      from hospitalization areas. The aim of this study was to find the differences
      between the clinical conditions at the time of hospitalization and when the
      patients were transferred to PICU. METHODS: Retrospective cohort study of 78
      children under 17 years of age with a hospital stay before their admission to the
      PICU. We measured respiratory, cardiovascular, neurological and metabolic
      conditions, when patients were admitted at hospitalization, and also for their
      admission to PICU. A evaluation of Pediatric Index of Mortality at the time of
      the admission to the PICU was applied. We analyzed the differences between those
      admitted before 24 hours of stay and those after 24 hours. RESULTS: 44 patients
      (56.4 %) were less than 24 hours in a hospital ward and they had more unstable
      symptoms since their admission; most of them were previously healthy infants with
      acute diseases or severe injuries. In those patients with more than 24 hours of
      stay (43.6 %), and with better conditions at admission, the decision was related
      to complications with a former disease (23.5 % oncologic patients). CONCLUSIONS:
      Medical conditions at the time of admission to a hospital could alert the medical
      staff for the early decision to transfer a patient to the PICU. Health history or
      previous diseases are important.

PMID- 24878089
TI  - [Potential conflicts of interest in biomedical publications].
AB  - In human communication and personal relations, there is the possibility of
      dissent and have a conflict related to the perception or acceptance of the
      content of a message. To reach an agreement, it is important that the
      communication between people is horizontal and bidirectional while the issue is
      being discussed, in order to bring together the interlocutors' expectations and
      interests. In the administration of services and goods, friendship and nepotism
      have been the most frequent forms of potential conflicts of interest. These
      behaviors arise when a person, like a civil servant or employee, feels influenced
      by personal considerations when he is doing his work and when he is making
      decisions. The conflict of perceived interested can be so harmful to the
      reputation and confidence of an organization, as the real existence of a conflict
      of interest. In some countries, the law obliges organisms to have codes of ethics
      that cover these aspects. Thus, it is desirable the incorporation of ethical
      principles and "moral competences" in the curricula of health professionals.
      Actually, in medicine and biomedical investigation, conflicts of interest are a
      condition related to clinicians and researchers, who distort their results and
      work to obtain personal or financial benefits. In the generation and transmission
      of knowledge, the circumstances determine if a conflict of interest exists, not
      the methodology, either the results of the investigation, not even the technology
      used on their diffusion. 

PMID- 24878090
TI  - [The role and importance of the microRNAs in the diagnosis and development of
      diseases].
AB  - MicroRNAs are small non-coding ribonucleic acids of endogenous nature. They
      persist in various groups of eukaryotes and perform critical functions during the
      development and the cell homeostasis. They have from 19 to 25 nucleotides in
      length and regulate the translation of the target RNA messenger (mRNA). MicroRNAs
      can inhibit its translation, stabilizing it or inducing its degradation. They
      regulate the genetic expression and are involved in the control of cellular
      functions (the differentiation, the proliferation, the apoptosis and the
      metabolism). They are also involved in the response to stress, the angiogenesis,
      the oncogenesis and in cardiovascular functions. That is the reason why their
      abnormal expressions are associated to many pathological conditions. The aim of
      this review was to describe the importance of microRNAs, their biological origin
      and their role in various diseases, such as cancer, diabetes, obesity, and
      neurological disorders. The microRNAs are an attractive therapeutic target
      because it has been observed that just one of them can regulate several genes and
      it could influence all the signaling route; besides, they could inhibit
      themselves in vivo without adverse effects related to the usual therapeutic
      agents. Since they can be detected in serum, plasma, urine and saliva samples in
      a stable, reproducible and consistent form between individuals of the same
      species, we expect them to be useful as biomarkers for the clinical diagnosis and
      the monitoring of diseases. 

PMID- 24878091
TI  - [Clinical research XXI. From the clinical judgment to survival analysis].
AB  - Decision making in health care implies knowledge of the clinical course of the
      disease. Knowing the course allows us to estimate the likelihood of occurrence of
      a phenomenon at a given time or its duration. Within the statistical models that
      allow us to have a summary measure to estimate the time of occurrence of a
      phenomenon in a given population are the linear regression (the outcome variable
      is continuous and normally distributed -time to the occurrence of the event-),
      logistic regression (outcome variable is dichotomous, and it is evaluated at one
      single interval), and survival curves (outcome event is dichotomous, and it can
      be evaluated at multiple intervals). The first reference we have of this type of
      analysis is the work of the astronomer Edmond Halley, an English physicist and
      mathematician, famous for the calculation of the appearance of the comet orbit,
      recognized as the first periodic comet (1P/Halley's Comet). Halley also
      contributed in the area of health to estimate the mortality rate for a Polish
      population. The survival curve allows us to estimate the probability of an event
      occurring at different intervals. Also, it leds us to estimate the median
      survival time of any phenomenon of interest (although the used term is survival,
      the outcome does not need to be death, it may be the occurrence of any other
      event). 

PMID- 24878092
TI  - [Educational status and life expectancy in patients with chronic non-communicable
      diseases].
AB  - BACKGROUND: Suffering a non communicable chronic disease in combination with low
      educational level and low economic income develops a synergy, which contributes
      to a poor prognostic about the expectancy of life. A better educational level may
      improve the life expectancy. The objective of this research was to explore this
      relation. METHODS: A retrospective cohort study from January 1, 1999, to December
      31, 2011, was performed. We included 2306 patients obtained from the information
      system in mortality of Family Medicine Unit 3 of the Instituto Mexicano del
      Seguro Social in Guadalajara, Jalisco. The main measures were average age-at
      death and educational level. We used Student's t, chi-squared test and relative
      risk (RR) calculations for statistical analysis. RESULTS: The average age-at
      death for those who had a low educational level (n = 1936) was 73.24 +/- 12.18
      years, while for those who had a satisfactory level of education (n = 370) was
      63.47 +/- 14.51 years, estimating a mean difference of 9.77 years with p < 0.001.
      Having a low educational level and not reaching life expectancy compared to the
      satisfactory level meant a RR = 0.24 (IC 95 % = 0.19, 0.30). The projected linear
      regression for each educational grade showed that patients lost 2.5 years of
      life. CONCLUSIONS: Diabetes accompanied by a low educational level showed a
      double probability of not reaching the expectation of life.

PMID- 24878093
TI  - [Clinical analysis of 200 cases of idiopathic thrombocytopenic purpura].
AB  - BACKGROUND: Idiopathic thrombocytopenic purpura is characterized by extravasation
      of blood into the subcutaneous tissue, mucous membranes or skin; it generates
      bleeding manifestations as ecchymotic lesions, petechiae of sudden onset,
      epistaxis, bleeding from the gums, and serious complications such as intracranial
      hemorrhage. This condition is due to a platelet destruction mediated by
      antibodies directed against the surface of the platelets. The objective is to
      present the clinical characteristics of patients with idiopathic thrombocytopenic
      purpura in a third level medical facility in Puebla, Mexico. METHODS: A
      descriptive study, which included 200 patients from the Hematology Service, was
      carried out. All patients included had the diagnosis of idiopathic
      thrombocytopenic purpura. We studied their clinical manifestations, type of
      diagnosis, as well as medical and/or surgical treatment. The statiscal analysis
      was made using descriptive measures. RESULTS: The entire sample (200 patients)
      had idiopathic thrombocytopenic purpura as a diagnosis established, 57 % had
      ecchymoses, 42 % petechiae, 23 % bleeding from the gums, 31.5 % epistaxis, 6.5 %
      abnormal uterine bleeding, 11 % malaise, 7.0 % hemorrhage, 0.5 % pruritus, 0.5 %
      seizures, 8 % two or more signs and symptoms and 73 % was asymptomatic when the
      diagnosis was established. CONCLUSIONS: Symptoms of idiopathic thrombocytopenic
      purpura are varied, a large percentage of patients can be processed unnoticed.
      The results described were similar to those reported in the literature.

PMID- 24878094
TI  - [Utility of a pneumatic system to transport erythrocyte concentrates: pilot
      study].
AB  - BACKGROUND: The transport systems of erythrocyte concentrates should be safe and
      modern. In this paper we analyzed the safety of one pneumatic system to transport
      erythrocyte concentrates from blood transfusion service to post-surgical therapy
      service. METHODS: We analyzed 50 erythrocyte concentrates; a sample of 1.5 mL of
      blood was drawn previously and after delivering the concentrated erythrocyte. The
      samples were placed in glass tubes to measure temperature, hemoglobin, hematocrit
      and extracellular potassium concentration. The average and range as univariate
      analysis and the Mann-Whitney U test as a bivariate analysis were done for
      statistical analysis. RESULTS: Statistical differences were not observed in the
      parameters measured. The temperature was not modified by the pneumatic delivery
      system. The data indicated no significant differences (p > 0.05) pre and post
      delivered samples in temperature, hemoglobin concentration, hematocrit level or
      extracellular potassium concentration. The estimated travel time for each sample
      was 22.88 seconds. CONCLUSIONS: The transport of erythrocyte concentrates through
      pneumatic delivery system did not change temperature conditions according to the
      current regulation. Indeed, the data did not show evidence that the cellular
      suspension underwent a spontaneous cellular lysis by sending erythrocyte
      concentrates through a pneumatic delivery system.

PMID- 24878095
TI  - [Nilotinib in patients with chronic myeloid leukemia without response to
      imatinib].
AB  - BACKGROUND: Resistance and intolerance to imatinib in patients with chronic
      myeloid leukemia requires alternative therapies. Nilotinib provides a choice as a
      second-line treatment. The objective of this report was to show the results of a
      group of patients with chronic myeloid leukemia who received nilotinib as a
      second-line treatment. METHODS: The medical records of 16 patients of both sexes,
      of any age, diagnosed with chronic myeloid leukemia, who received nilotinib as a
      second-line treatment, were reviewed. All of them had received imatinib prior as
      first-line treatment; the causes to switch to nilotinib were intolerance,
      resistance and clinical progression of leukemia. RESULTS: The sample was of 16
      patients, who achieved at least a hematologic response; 10 were males (62.5%).
      The age range was 24 to 75 years. Two patients received nilotinib due to
      intolerance to imatinib; seven due to resistance to imatinib and seven due to
      lack of response. There was response in the two patients who received nilotinib
      due to intolerance. One patient died five months after starting nilotinib due to
      progression of leukemia; four patients achieved major molecular response, two
      patients had reduced expression of BCR-ABL gene. Six patients continued with high
      expression of BCR-ABL gene; two of them carrying M244V mutation, and one with a
      complex karyotype with numerical and structural alterations. CONCLUSIONS:
      Nilotinib is an option for patients with intolerance or resistance to imatinib.

PMID- 24878096
TI  - [Organic and functional limitations due to milking phenomenon: a clinical case
      report].
AB  - BACKGROUND: The incidence of milking phenomenon is between 0.6 and 4 % in
      angiographic series; however, autopsy studies raise the incidence of myocardial
      bridges up to 85 %. This malformation goes unnoticed in most cases but can have a
      big impact on personal and professional level. The objective was to present an
      example of milking phenomenon with disability and professional consequences.
      CLINICAL CASE: Male, 44 years old, bricklayer and farmhand laborer. He referred
      tonsillectomy and osteoarthritis and being a smoker of 10 cigarettes per day,
      drinking 2-3 cups of coffee daily and 2-3 glasses of wine at the weekends. The
      primary care physician referred him to cardiologist with suspicion of arrhythmia.
      The cardiology service report mentioned electrocardiogram at sinusal rhythm, 90
      beats per minute and incomplete right bundle-branch block. At ergonomics test, in
      the first stage of Bruce protocol, the patient's development of hypertensive
      crisis suggested a milking phenomenon. Finally, the diagnosis was established by
      angiographic studies with left common branch, circumflex coronary artery, right
      coronary artery and anterior descendent artery, without evidence of pathology but
      it was seen systolic compression on the medial segment. The case was concluded by
      the disability assessment team, recognizing a total permanent disability with
      limitations for activities requiring moderate physical efforts. CONCLUSIONS: The
      milking phenomenon diagnosis that could be related with ischemic heart disease is
      by angiography. Finally, the patient ended with total permanent disability.

PMID- 24878097
TI  - [Dentigerous cyst in a pediatric patient with acute lymphoblastic leukemia type
      1].
AB  - OBJECTIVE: To report medical and surgical treatment in a patient with acute
      lymphoblastic leukemia type 1 who developed a dangerous cyst. CLINICAL CASE: A
      male of 8 years with acute lymphoblastic leukemia type 1, whose treatment was in
      induction. In one month, the patient presented a facial asymmetry due to
      mandibular growth and acute pain, hyperthermia and malaise. In the examination,
      we identified lip parestesia, a second temporal molar treated with chromium steel
      and expansion involving the cortical of the lateral permanent incisive until the
      first permanent molar was identified. Since we suspected of bone metastasis, we
      performed an orthopantomography. We established the diagnosis of dentigerous
      cyst. Enucleation, curettage, and extraction of decay teeth were done in order to
      avoid and prevent infectious sources. CONCLUSIONS: The most frequent clinical
      manifestations of acute lymphoblastic leukemia are anemia, leukopenia, and
      thrombocytopenia. This leukemia may be manifested also as infiltration of the jaw
      bone. In this case, the results showed no presence of bone metastasis. As a first
      step before to begin treatment, the physician ought to make sure that the patient
      is free of infectious processes anywhere that may influence the clinical
      development of leukemia. Due to the surgical intervention and to a successful
      bone marrow transplant, the patient is on remission.

PMID- 24878098
TI  - [Pregnancy and myeloid leukemia treated with imatinib. Development and monitoring
      of a patient].
AB  - BACKGROUND: Imatinib has changed the natural history of chronic myeloid leukemia.
      There are women with chronic myeloid leukemia in reproductive age with pregnancy
      desires. The aim of this case was to report the course and outcome of pregnancy
      in a patient with chronic myeloid leukemia diagnosis treated with imatinib.
      CLINICAL CASE: A 32 year old female with diagnosis of chronic myeloid leukemia
      with follow-up of 11 years. She received standard treatment, but she reported
      poor adherence; therefore, she received imatinib therapy two years after the
      diagnosis. The patient stopped the treatment herself because she was looking to
      be pregnant. She presented amenorrhea, which lasted for six weeks; pregnancy was
      confirmed. During a period of 10 months, she remained untreated and there were no
      symptoms of leukemia progression. The pregnancy was terminated by cesarean
      section at 35.5 weeks of gestation. The product was born healthy. In the post
      cesarean visit, the lab showed a cell blood count which reported: hemoglobin 8.7
      g/dL, hematocrit 25 %, white blood cell 22,000/mL, platelets 170,000/mL. Since
      October the patient resumed imatinib 600 mg/day. CONCLUSIONS: The prolonged
      period of treatment with imatinib had no effect on the pregnancy and the product.
      The molecular monitoring showed the need to reinstall the treatment once the
      pregnancy finished. The efficacy and safety of treatment allows patients to
      fulfill life projects that seemed distant in other time.

PMID- 24878099
TI  - [Psychiatric Hospital San Juan de Dios. One hundred years later].
AB  - Mental health and psychiatric diseases have always attracted people's and health
      authorities' attention due to its magical approach, the lack of knowledge that
      surrounds them, and, at the same time, the religious fear they provoke. Both have
      played an important role in the history of humanity, of public health politics,
      and of physicians. The places where psychiatric patients were treated are of
      historical interest, because through the historical knowledge we can identify an
      approach from the science and the health policies that prevailed in each age. At
      the beginning of the 20th century, it was developed in Mexico a new model of
      hospital care attention to psychiatric patients. La Casa de Salud San Juan de
      Dios para Pacientes Alienados is an example; the concept "alienated patients"
      suggests a social and cultural perspective. This paper presents a chronological
      type description of one of the major institutions involved in mental health care
      in Mexico. Similarly, it shows a review of the events that affected the religious
      order San Juan de Dios from 1901 to 2012, when the hospitaller order was
      reinstated in Mexico and established the Casa de Salud San Juan de Dios para
      Pacientes Alienados in the town of Zapopan, Jalisco, institution that exists up
      to the present day and keeps participating in the mental health care in the state
      of Jalisco, with the current name of Servicios de Salud San Juan de Dios. 

PMID- 24878100
TI  - [Topographical-medical study on the Virgin of Guadalupe's ayate. Unpublished
      paper from a New Spanish sage].
AB  - In the context of medical studies, the topographic aspect (a study about the
      special circumstances that contributes to the beginning, develop, and ending of
      diseases belonging to a country) acquired particular significance in New Spain
      through the work of Diego Cisneros (1618). Juan de Melgarejo, professor,
      protophysician, priest, and author of two medical writings, continued with the
      work of Cisneros. The one that concerns us in this paper is called Parecer que
      ejecuto el Dr. D. Juan de Melgarejo por mandato de su Santidad y orden del Proto
      Medicato sobre la incorrupcion del Ayate de Maria Santisima de Guadalupe, por los
      anos de 1666. This text remained unpublished and it is closely related to the
      line of Melgarejo's works on the Virgin of Guadalupe. In this work he analyzes
      the ayate (cloak) of Juan Diego from a topographic perspective inserted in
      theoretical and experimental aspects of the hippocratical-galenic slope that
      prevailed in the medicine perspective of the Baroque New Spain. This research
      includes aspects on the university education of the author and regarding his
      tasks as protophysician, one of which was, precisely, the development of the
      Guadalupean manuscript. All the sources we have used are original. They come from
      Mexico's General Archive of the Nation, and they all were interpreted by the
      author. They show the training given by doctors at the Royal and Pontifical
      University of Mexico and the link between this and the tasks of the Royal
      Protomedicato Tribunal. 

PMID- 24878101
TI  - A systematic approach toward building a fully operational clinical competency
      committee.
AB  - BACKGROUND: The Accreditation Council for Graduate Medical Education has offered
      minimal guidelines for the creation and implementation of clinical competency
      committees (CCCs). As surgical residency programs may differ greatly in terms of
      size and structure, requirements that are too specific throughout the process
      could place some programs at a great disadvantage. OBJECTIVE: The purpose of this
      article is to address some of the common considerations all surgery residency
      programs will face. The creation of standard operating procedures for the CCCs
      will allow each committee to develop internal consistency, improve productivity,
      maintain efficiency and quality control, facilitate training of new committee
      members, and cross-train other faculty and residents on the key processes to
      provide transparency. METHODS: This article offers recommendations on the 3 key
      areas of CCC implementation: the prereview, resident milestone review, and the
      postreview processes. Specific components related to shifting culture, committee
      membership and terms, assessing available evidence, and review dissemination are
      outlined, and example scenarios are provided throughout the article. CONCLUSION:
      With the implementation of CCCs and the milestones project, residency programs
      have an opportunity to improve the overall quality of decision making regarding
      residents' promotion to the next training level or independent practice. CCCs
      will undoubtedly be confronted with numerous challenges, as they implement the
      milestones project and are faced with the need to make multiple changes.
      Therefore, implementing milestones should be viewed as a goal to be accomplished
      over the long term.

PMID- 24878102
TI  - Inhibitory processes in visual perception: a bilingual advantage.
AB  - Bilingual inhibitory control advantages are well established. An open question is
      whether inhibitory superiority also extends to visual perceptual phenomena that
      involve inhibitory processes. This research used ambiguous figures to assess
      inhibitory bilingual superiority in 3-, 4-, and 5-year-old mono- and bilingual
      children (N=141). Findings show that bilinguals across all ages are superior in
      inhibiting a prevalent interpretation of an ambiguous figure to perceive the
      alternative interpretation. In contrast, mono- and bilinguals revealed no
      differences in understanding that an ambiguous figure can have two distinct
      referents. Together, these results suggest that early bilingual inhibitory
      control superiority is also evident in visual perception. Bilinguals' conceptual
      understanding of figure ambiguity is comparable to that of their monolingual
      peers. 

PMID- 24878103
TI  - Comment on "football-specific fitness testing: adding value or confirming the
      evidence?".
AB  - The recent point-counter-point exchange arising from the article by Mendez
      Villanueva and Buchheit (2013) (Football-specific fitness testing: Adding value
      or confirming the evidence? Journal of Sports Sciences, 31, 1503-1508) has
      generated an interesting debate on the real-world utility of fitness testing in
      professional association football (soccer). In the present authors' opinion, this
      exchange could also have been placed more in the context of the physical testing
      and subsequent benchmark profiling of the youth player within elite academy
      talent identification and development processes. This point is further
      strengthened by the current media debate at the time of writing on the
      development of elite youth football players in England and the Elite Player
      Performance Plan or EPPP (The Premier League. (2011). Elite Player Performance
      Plan. London: Author) published by the English Premier League as part of a vision
      for the future development of youth football in the League and throughout the
      English professional game. The EPPP recommends the implementation of a national
      database to enable comparison of Academy player performances against national
      physical testing "benchmark" profiles. In continuing the above debate, this
      letter questions the real-world utility and potential pitfalls of nationwide
      athletic benchmark profiling programmes for elite youth football.

PMID- 24878104
TI  - P450 enzyme-inducing and non-enzyme-inducing antiepileptic drugs for seizure
      prophylaxis after glioma resection surgery: a meta-analysis.
AB  - PURPOSE: The prognoses of seizure treatment with P450 enzyme-inducing and non
      enzyme-inducing antiepileptic drugs after glioma resection surgery were
      investigated across several clinical studies. However, the results of these
      studies are inconsistent. We examined the relevant studies and conducted a meta
      analysis of these two types of anti-epileptic drugs. METHODS: A bibliography
      search using the EMBASE, MEDLINE, ClinicalTrials.gov, and Cochrane Central
      Register of Controlled Trials databases was performed to identify potentially
      relevant articles and conference abstracts that investigated the effects of non
      enzyme-inducing antiepileptic drugs (NEIAEDs) and enzyme-inducing antiepileptic
      drugs (EIAEDs) on the seizure prognoses of glioma patients. RESULTS: One RCT
      study and five observational studies were included. Pooled estimates of the
      relative risks (OR) and 95% confidence intervals (CI) were calculated. The pooled
      odds ratio for NEIAEDs vs. EIAEDs for patients with glioma was 1.12 (95% CI=0.70
      2.10). The pooled odds ratio for NEIAEDs vs. EIAEDs for low-grade gliomas was
      1.77 (95% CI=0.71-4.40). The pooled odds ratio for LEV vs. PHY was 1.459 (95%
      CI=0.731-2.910). CONCLUSIONS: No significant difference between the efficacies of
      P450 enzyme-inducing and non-enzyme-inducing antiepileptic drugs for prophylactic
      late seizure treatment was observed. However, few RCTs were available, and the
      acquisition of further evidence through high-quality RCTs is highly recommended.

PMID- 24878105
TI  - A mixed-methods exploration of the contraceptive experiences of female teens with
      epilepsy.
AB  - PURPOSE: We explored the contraceptive experiences of female teens with epilepsy,
      including their knowledge and perceptions of interactions between antiepileptic
      drugs and hormonal contraception and contraceptive decision-making processes.
      METHOD: From November 2012 to May 2013, we conducted one online survey (n=114)
      and 12 online focus group discussions (n=26) with female teens with epilepsy
      about their contraceptive experiences and unmet needs. Survey data were analyzed
      using descriptive statistics and focus group transcripts were analyzed
      thematically using modified grounded theory methods. RESULTS: Both survey and
      focus group participants reported believing that interactions between epilepsy
      medications and hormonal contraceptives could lead to reductions in contraceptive
      efficacy and seizure control. However, their knowledge about these types of
      medication interactions was often incomplete. Many study participants viewed
      contraceptive decision making as a difficult process, and some participants
      reported avoiding hormonal contraceptives because of potential interactions with
      antiepileptic drugs. Study participants reported relying on health care providers
      and parents for contraceptive decision-making support. Focus group participants
      also reported they wanted health care providers to provide more in-depth and
      comprehensive counseling about contraception, and that they desired peer support
      with contraceptive decisions. CONCLUSION: The ability to make informed
      contraceptive decisions is important for teens with epilepsy as interactions
      between anti-epileptic drugs and hormonal contraceptives can impact seizure
      occurrence and lead to an increased risk of unplanned pregnancy. Guidance for
      providers offering contraceptive care to this population is needed, as well as a
      contraceptive support tool that empowers teens with epilepsy to advocate for
      desired health care.

PMID- 24878106
TI  - A pilot of clinical performance indicators for suspected childhood epilepsies.
AB  - PURPOSE: In response to continuing concerns regarding the quality and equality of
      care for children and young people, the British Paediatric Neurology Association
      (BPNA) has supported the development of practical and meaningful audit to support
      quality improvement. METHOD: In 2006, the Children's Epilepsy Workstream in Trent
      (CEWT) coordinated a retrospective multi-service audit of paediatric epilepsy
      care against NICE and SIGN guidelines. This aimed to both facilitate quality
      improvements for participating services and act as a pilot for future potential
      national audits. RESULTS: The audit was achieved in 4 hospital services using
      prospective and retrospective ascertainment methods. 12 performance indicators
      were applied to each cohort. Overall 54% (12/22) of children with epilepsy had
      input from a paediatrician with "expertise" and 23% (5/22) had input from an
      epilepsy specialist nurse. CONCLUSION: Audit can be developed for epilepsies that
      delivers standardised quality metrics against national recommendations. As well
      as supporting local quality improvement initiatives, comparative and aggregate
      data can be produced to potentially give regional and national perspectives. The
      results and experience describe the journey towards the 2009-2012 Epilepsy 12 UK
      multicentre epilepsy audit.

PMID- 24878107
TI  - Association between STAT5 polymorphisms and glioblastoma risk in Han Chinese
      population.
AB  - The aim of this study was to investigate the associations between STAT5 gene
      polymorphisms and glioblastoma (GBM) risk predisposition. We undertook a case
      control study to analyze two STAT5 polymorphisms (STAT5a rs11079041 and STAT5b
      rs2293157) in a Han Chinese population, by extraction of genomic DNA from the
      peripheral blood of 328 patients with glioma and 342 control participants, and
      performed STAT5 genotyping using DNA sequencing. The obtained results indicated
      that overall, no statistically significant association was observed in STAT5a
      rs11079041. Nevertheless, STAT5b rs2293157 G/T genotype was at increased risk of
      glioma (P=0.001). Furthermore, rs2293157T allele was more significantly
      prognostic in patients suffering from glioblastoma compared to other subtypes of
      gliomas (P<0.001; odds ratio (OR)=5.14, CI 95%: 2.70-9.79). These findings led us
      to conclude that polymorphism in STAT5b rs2293157 G/T was observed to be
      associated with susceptibility of glioblastoma. Nevertheless, further
      investigation with a later confirmation in another ethnical or geographical
      cohort is required.

PMID- 24878108
TI  - Different detectability of cyclooxygenase-2 (COX-2) protein in standard paraffin
      sections and tissue microarrays of human melanomas and naevi - comparative study.
AB  - Cyclooxygenase-2 (COX-2), overexpressed in many types of human cancer, may be a
      valuable marker for human melanoma. However, there are discrepancies between
      expression levels detected by different groups. The majority of the studies were
      carried out using standard paraffin sections. Tissue microarrays (TMAs) might
      enable analysis of COX-2 expression in numerous lesions. Our study assesses to
      what extent reprocessing of tissue samples used for preparing TMAs may influence
      reproducibility of data obtained for standard sections. The study included TMAs
      and standard histopathologic sections. COX-2 was detected by immunohistochemistry
      with two primary antibodies targeting different epitopes. COX-2 expression levels
      detected with both antibodies in standard sections were similar as in our
      previous study. Surprisingly, results obtained in TMAs were significantly
      different. While one of the antibodies yielded for TMAs results similar to
      standard sections, COX-2 expression levels found with the second antibody were
      very low and expression patterns strikingly different from those observed for
      standard sections and for both TMAs studied with the first antibody. Good
      performance of the antibodies found in standard sections of human skin and
      melanocytic lesions does not guarantee similar results in TMAs. The finding
      discloses a new aspect of immunohistochemical assays involving TMAs.

PMID- 24878109
TI  - Life-history implications of the allometric scaling of growth.
AB  - Several phenomenological descriptions, such as the von Bertalanffy growth model,
      have been widely used to describe size-at-age and individual growth across a
      diverse range of organisms. However, for modelling life histories, as opposed to
      just growth, biologically and mechanistically meaningful growth models, based on
      allocation decisions, have become increasingly important. This is because fitness
      is determined by survival and reproduction, which are not addressed directly in
      phenomenological growth models. To elucidate these considerations, we take as a
      starting point the biphasic growth model by Quince et al. (2008a, J. Theor. Biol.
      254:197) which has the advantage that the underlying allometric scaling of net
      energy intake can be freely chosen. First, we reformulate this model such that
      individual size is given in meaningful units of length and weight, facilitating
      the model's interpretation and application. Second, we show that even though
      different allometric scaling relationships can produce practically identical
      growth trajectories, the accompanying reproductive investments are highly
      dependent on the chosen allometric exponent. Third, we demonstrate how this
      dependence has dramatic consequences for evolutionary predictions, in particular
      with regard to the age and size at maturation. These findings have considerable
      practical relevance, because empirically observed allometric exponents are often
      uncertain and systematically differ from those assumed in current standard growth
      models. 

PMID- 24878110
TI  - Construction of a mathematical model for tuberculosis transmission in highly
      endemic regions of the Asia-Pacific.
AB  - We present a mathematical model to simulate tuberculosis (TB) transmission in
      highly endemic regions of the Asia-Pacific, where epidemiology does not appear to
      be primarily driven by HIV-coinfection. The ten-compartment deterministic model
      captures many of the observed phenomena important to disease dynamics, including
      partial and temporary vaccine efficacy, declining risk of active disease
      following infection, the possibility of reinfection both during the infection
      latent period and after treatment, multidrug resistant TB (MDR-TB) and de novo
      resistance during treatment. We found that the model could not be calibrated to
      the estimated incidence rate without allowing for reinfection during latency, and
      that even in the presence of a moderate fitness cost and a lower value of R0, MDR
      TB becomes the dominant strain at equilibrium. Of the modifiable programmatic
      parameters, the rate of detection and treatment commencement was the most
      important determinant of disease rates with each respective strain, while
      vaccination rates were less important. Improved treatment of drug-susceptible TB
      did not result in decreased rates of MDR-TB through prevention of de novo
      resistance, but rather resulted in a modest increase in MDR-TB through strain
      replacement. This was due to the considerably greater relative contribution of
      community transmission to MDR-TB incidence, by comparison to de novo
      amplification of resistance in previously susceptible strains. 

PMID- 24878111
TI  - Simulation of the resonance Raman spectrum for uracil.
AB  - The resonance Raman spectrum of uracil is simulated using the Herzberg-Teller
      short-time dynamics formalism. The ground-state geometry is optimized at the
      levels of PBE0/aug-cc-pVTZ and B3LYP/aug-cc-pVTZ, respectively. The gradient of
      the bright excited state is computed using time-dependent density functional
      theory and spin-flip time-dependent density functional theory. The excited-state
      calculations are carried out in both the gas phase and implicit water using the
      conductor-like polarizable continuum model. The ground-state equilibrium
      structure is found to impact the resulting resonance Raman spectrum
      significantly. The simulated resonance Raman spectrum using the long-range
      corrected functionals, that is, CAMB3LYP and LC-BLYP, and based on the PBE0/aug
      cc-pVTZ optimized ground-state structure shows better agreement with the
      experimental spectrum than using standard hybrid functionals, that is, PBE0 and
      B3LYP. The solvation effect leads to a change in the energetic order of the n ->
      pi* and pi -> pi* excited states, and it improves the agreement with the
      experimental spectrum, especially with regard to the relative intensities of the
      peaks with frequencies greater than 1600 cm(-1). 

PMID- 24878113
TI  - Synthesis and characterization of metal-organic framework-74 containing 2, 4, 6,
      8, and 10 different metals.
AB  - Metal-organic frameworks (MOFs) containing more than two kinds of metal ions
      mixed in one secondary building unit are rare because the synthesis often yields
      mixed MOF phases rather than a pure phase of a mixed-metal MOF (MM-MOF). In this
      study, we use a one-pot reaction to make microcrystalline MOF-74 [M2(DOT); DOT =
      dioxidoterephthalate] with 2 (Mg and Co), 4 (Mg, Co, Ni, and Zn), 6 (Mg, Sr, Mn,
      Co, Ni, and Zn), 8 (Mg, Ca, Sr, Mn, Fe, Co, Ni, and Zn), and 10 (Mg, Ca, Sr, Ba,
      Mn, Fe, Co, Ni, Zn, and Cd) different kinds of divalent metals. The powder X-ray
      diffraction patterns of MM-MOF-74 were identical with those of single-metal MOF
      74, and no amorphous phases were found by scanning electron microscopy. The
      successful preparation of guest-free MM-MOF-74 samples was confirmed by N2
      adsorption measurements. Elemental analysis data also support the fact that all
      metal ions used in the MOF synthesis are incorporated within the same MOF-74
      structure. Energy-dispersive X-ray spectroscopies indicate that metal ions are
      heterogeneously distributed within each of the crystalline particles. This
      approach is also employed to incorporate metal ions (i.e., Ca, Sr, Ba, and Cd)
      from which the parent MOF structure could not be made as a single-metal
      containing MOF. 

PMID- 24878114
TI  - Fluorometric assessment of acetaminophen-induced toxicity in rat hepatocyte
      spheroids seeded on micro-space cell culture plates.
AB  - Hepatotoxicity induced by the metabolic activation of drugs is a major concern in
      drug discovery and development. Three-dimensional (3-D) cultures of hepatocyte
      spheroids may be superior to monolayer cultures for evaluating drug metabolism
      and toxicity because hepatocytes in spheroids maintain the expression of various
      metabolizing enzymes and transporters, such as cytochrome P450 (CYP). In this
      study, we examined the hepatotoxicity due to metabolic activation of
      acetaminophen (APAP) using fluorescent indicators of cell viability and
      intracellular levels of glutathione (GSH) in rat hepatocyte spheroids grown on
      micro-space cell culture plates. The mRNA expression levels of some drug
      metabolizing enzymes were maintained during culture. Additionally, this culture
      system was compatible with microfluorometric imaging under confocal laser
      scanning microscopy. APAP induced a decrease in intracellular ATP at 10mM, which
      was blocked by the CYP inhibitor 1-aminobenzotriazole (ABT). APAP (10mM, 24h)
      decreased the levels of both intracellular ATP and GSH, and GSH-conjugated APAP
      (APAP-GSH) were formed. All three effects were blocked by ABT, confirming a
      contribution of APAP metabolic activation by CYP to spheroid toxicity.
      Fluorometric imaging of hepatocyte spheroids on micro-space cell culture plates
      may allow the screening of drug-induced hepatotoxicity during pharmaceutical
      development. 

PMID- 24878115
TI  - Cytotoxic evaluation of nanostructured zinc oxide (ZnO) thin films and leachates.
AB  - Nanostructured ZnO films have potential use as coatings on medical devices and
      food packaging due to their antimicrobial and UV-protection properties. However,
      their influence on mammalian cells during clinical use is not fully understood.
      This study investigated the potential cytotoxicity of ZnO thin films in RAW 264.7
      macrophages. ZnO thin films (~96nm thick with a 50nm grain) were deposited onto
      silicon wafers using pulsed laser deposition. Cells grown directly on ZnO thin
      film coatings exhibited less toxicity than cells exposed to extracts of the
      coatings. Cells on ZnO thin films exhibited a 43% and 68% decrease in cell
      viability using the MTT and 7-AAD/Annexin V flow cytometry assays, respectively,
      after a 24-h exposure as compared to controls. Undiluted 100% 24- and 48-h
      extracts decreased viability by 89%, increased cell death by LDH release to 76%
      24h after treatment, and increased ROS after 5-24h of exposure. In contrast, no
      cytotoxicity or ROS were observed for 25% and 50% extracts, indicating a
      tolerable concentration. Roughly 24 and 34MUg/m(2) Zn leached off the surfaces
      after 24 and 48h of incubation, respectively. ZnO coatings may produce gradual
      ion release which becomes toxic after a certain level and should be evaluated
      using both direct exposure and extraction methods. 

PMID- 24878116
TI  - Experimental and solid-state computational study of structural and dynamic
      properties in the equilibrium form of temazepam.
AB  - Structural properties and rotational dynamics of methyl groups in the most stable
      form of temazepam were investigated by means of (13)C CP MAS NMR, quasielastic
      neutron scattering (QENS), and (1)H NMR spin-lattice relaxation methods. The QENS
      and (1)H NMR studies reveal the inequivalency of methyl groups, delivering their
      activation parameters. The structural properties of the system were explored in
      frame of periodic density functional theory (DFT) computations, giving insight
      into the reorientational barriers and providing understanding of the solid-state
      NMR results. The theoretical computations are shedding light on the
      intermolecular interactions along their relation with particular asymmetric
      structural units. 

PMID- 24878117
TI  - Efficacy of pre-hospital use of glycoprotein IIb/IIIa inhibitors in ST-segment
      elevation myocardial infarction before mechanical reperfusion in a rapid-transfer
      network (from the Acute Myocardial Infarction Registry of Brittany).
AB  - Previous studies investigating prehospital use of glycoprotein IIb/IIIa
      inhibitors (GPIs) in patients with ST-segment elevation myocardial infarction
      reached conflicting conclusions. The benefit of this strategy in addition to in
      ambulance loading of dual-antiplatelet therapy remains controversial. The aim of
      this study was to analyze data from a prospective registry of patients with ST
      segment elevation myocardial infarctions admitted <24 hours after symptom onset
      (July 2006 to May 2012). A total of 2,052 patients managed in a physician-staffed
      mobile intensive care unit (MICU)<12 hours after symptom onset and scheduled for
      primary percutaneous coronary intervention (PPCI) were retrospectively included.
      Patients who received GPIs in the MICU were compared with those who did not. The
      primary end point was infarct-related artery patency, defined as pre-PPCI
      Thrombolysis In Myocardial Infarction (TIMI) flow grade 3. GPIs were administered
      in the MICU to 737 patients (36%), including 430<2 hours after symptom onset, and
      1,315 patients (64%) did not received prehospital GPIs. Pre-PPCI TIMI flow grade
      3 rate was lower in patients treated in the MICU (17.2% vs 21.3%, p=0.03) because
      of patients treated >2 hours after symptom onset, of whom only 12.7% reached the
      primary end point. There was no significant difference between groups in the rate
      of in-hospital major adverse cardiac events. In conclusion, prehospital GPI use
      in patients with ST-segment elevation myocardial infarctions<12 hours after
      symptom onset scheduled for PPCI neither improved pre-PPCI infarct-related artery
      patency nor reduced in-hospital major adverse cardiac events.

PMID- 24878118
TI  - Lung function and heart disease in American Indian adults with high frequency of
      metabolic abnormalities (from the Strong Heart Study).
AB  - The associations of pulmonary function with cardiovascular disease (CVD)
      independent of diabetes mellitus (DM) and metabolic syndrome have not been
      examined in a population-based setting. We examined prevalence and incidence CVD
      in relation to lower pulmonary function in the Strong Heart Study second
      examination (1993 to 1995) in 352 CVD and 2,873 non-CVD adults free of overt lung
      disease (mean age 60 years). Lung function was assessed by standard spirometry.
      Participants with metabolic syndrome or DM with or without CVD had lower
      pulmonary function than participants without these conditions after adjustment
      for hypertension, age, gender, abdominal obesity, smoking, physical activity
      index, and study field center. CVD participants with DM had significantly lower
      forced vital capacity than participants with CVD alone. Significant associations
      were observed between reduced pulmonary function, preclinical CVD, and prevalent
      CVD after adjustment for multiple CVD risk factors. During follow-up (median 13.3
      years), pulmonary function did not predict CVD incidence, it predicted CVD
      mortality. Among 3,225 participants, 412 (298 without baseline CVD) died from CVD
      by the end of 2008. In models adjusted for multiple CVD risk factors, DM,
      metabolic syndrome, and baseline CVD, compared with highest quartile of lung
      function, lower lung function predicted CVD mortality (relative risk up to 1.5,
      95% confidence interval 1.1 to 2.0, p<0.05). In conclusion, a population with a
      high prevalence of DM and metabolic syndrome and lower lung function was
      independently associated with prevalent clinical and preclinical CVD, and its
      impairment predicted CVD mortality. Additional research is needed to identify
      mechanisms linking metabolic abnormalities, low lung function, and CVD.

PMID- 24878119
TI  - Comparison of hybrid coronary revascularization versus coronary artery bypass
      grafting in patients>=65 years with multivessel coronary artery disease.
AB  - Hybrid coronary revascularization (HCR) combines minimally invasive left internal
      mammary artery-to-left anterior descending coronary artery grafting with
      percutaneous coronary intervention of non-left anterior descending coronary
      arteries. The safety and efficacy of HCR in patients>=65 years of age is unknown.
      In this study, patients aged>=65 years were included who underwent HCR at an
      academic center from October 2003 to September 2013. These patients were matched
      1:4 to similar patients treated with coronary artery bypass grafting (CABG) using
      a propensity-score matching algorithm. Conditional logistic regression and Cox
      regression stratified on matched pairs were performed to evaluate the association
      between HCR and CABG, and 30-day major adverse cardiovascular and cerebrovascular
      events (a composite of mortality, myocardial infarction, and stroke),
      periprocedural complications, and 3-year all-cause mortality. Of 715 patients
      (143 of whom underwent HCR and 572 CABG) in the propensity score-matched cohort,
      rates of 30-day major adverse cardiovascular and cerebrovascular events were
      comparable after HCR and CABG (5.6% vs 3.8%, odds ratio 1.46, 95% confidence
      interval 0.65 to 3.27, p=0.36). Compared with CABG, HCR resulted in fewer
      procedural complications (9.1% vs 18.2%, p=0.018), fewer blood transfusions
      (28.0% vs 53.3%, p<0.0001), less chest tube drainage (838+/-484 vs 1,100+/-579
      cm3, p<0.001), and shorter lengths of stay (<5 days: 45.5% vs 27.4%, p=0.001).
      Over a 3-year follow-up period, mortality rates were similar after HCR and CABG
      (13.2% vs 16.6%, hazard ratio 0.81, 95% confidence interval 0.46 to 1.43,
      p=0.47). Subgroup analyses in high-risk patients (Charlson index>=6, age>=75
      years) rendered similar results. In conclusion, although the present data are
      limited, we found that in older patients, the use of HCR is safe, has fewer
      procedural complications, entails less blood product use, and results in faster
      recovery with similar longitudinal outcomes relative to conventional CABG.

PMID- 24878112
TI  - Neurodevelopmental outcomes in HIV-exposed-uninfected children versus those not
      exposed to HIV.
AB  - Human immunodeficiency virus (HIV)-negative children born to HIV-infected mothers
      may exhibit differences in neurodevelopment (ND) compared to age- and gender
      matched controls whose lives have not been affected by HIV. This could occur due
      to exposure to HIV and antiretroviral agents in utero and perinatally, or
      differences in the environment in which they grow up. This study assessed
      neurodevelopmental outcomes in HIV-exposed uninfected (HEU) and HIV-unexposed
      uninfected (HUU) children enrolled as controls in a multicenter ND study from
      Thailand and Cambodia. One hundred sixty HEU and 167 HUU children completed a
      neurodevelopmental assessment using the Beery Visual Motor Integration (VMI)
      test, Color Trails, Perdue Pegboard, and Child Behavior Checklist (CBCL). Thai
      children (n = 202) also completed the Wechsler Intelligence Scale (IQ) and
      Stanford-Binet II memory tests. In analyses adjusted for caregiver education,
      parent as caregiver, household income, age, and ethnicity, statistically
      significant lower scores were seen on verbal IQ (VIQ), full-scale IQ (FSIQ), and
      Binet Bead Memory among HEU compared to HUU. The mean (95% CI) differences were 
      6.13 (-10.3 to -1.96), p = 0.004; -4.57 (-8.80 to -0.35), p = 0.03; and -3.72 (
      6.57 to -0.88), p = 0.01 for VIQ, FSIQ, and Binet Bead Memory, respectively. We
      observed no significant differences in performance IQ, other Binet memory
      domains, Color Trail, Perdue Pegboard, Beery VMI, or CBCL test scores. We
      conclude that HEU children evidence reductions in some neurodevelopmental
      outcomes compared to HUU; however, these differences are small and it remains
      unclear to what extent they have immediate and long-term clinical significance. 

PMID- 24878120
TI  - Perioperative complications after noncardiac surgery in patients with insertion
      of second-generation drug-eluting stents.
AB  - The perioperative outcomes of noncardiac surgery in patients who have received
      second-generation drug-eluting stents (DESs) have received limited study. We
      reviewed the medical records of 1,748 consecutive patients who received DES at
      our institution (1,789 procedures) from January 1, 2009, to July 1, 2012, to
      determine the outcomes of subsequent noncardiac surgery. During a median follow
      up of 43 months, 221 patients underwent 345 noncardiac surgeries (138 low risk,
      130 intermediate risk, and 77 high risk), of which 278 were in patients with
      previous second-generation DES implantation. The incidence of noncardiac surgery
      in patients with previous second-generation DES implantation was 4.5% at 1 year,
      11.6% at 2 years, and 15.2% at 3 years. The mean time from stent implantation to
      surgery was 21+/-12.9 months. Mean age was 66+/-8 years, 99% were men, and 11%
      had a perioperative complication, including 5.8% major bleeding, 2.5% acute
      kidney injury, 2.2% major adverse cardiac event, and 1.4% stroke. Perioperative
      stent thrombosis occurred in 2 patients (0.7%, 95% confidence interval 0.2% to
      2.6%): 1 patient had received a DES 14 months before surgery and had stent
      thrombosis on the day of surgery and the other had a DES implanted 21 months
      before surgery and developed stent thrombosis the day after surgery. In
      conclusion, the incidence of perioperative complications with noncardiac surgery
      after second-generation DES implantation was 11% and consisted mainly of bleeding
      (5.8%). The incidence of definite stent thrombosis was 0.7%.

PMID- 24878121
TI  - New classification scheme for atrial fibrillation symptom severity and burden.
AB  - Although atrial fibrillation (AF) symptom severity is used to guide clinical
      care, a simple, standardized assessment tool is not available for routine
      clinical use. We sought to develop and validate a patient-generated score and
      classification scheme for AF-related symptom severity and burden. Atrial
      Fibrillation Symptom and Burden, a simple 2-part questionnaire, was designed to
      assess (1) AF symptom severity using 8 questions to determine how symptoms affect
      daily life and (2) AF burden using 6 questions to measure AF frequency, duration,
      and health-care utilization. The resulting score was used to classify patients
      into 4 classes of symptom and burden severity. Patients were asked to complete
      the questionnaire, a survey evaluating the questionnaire, and an Short Form-12v2
      generic health-related quality-of-life form. Validation of the questionnaire
      included assessments of its reliability and construct and known groups validity.
      The strength of interrater agreement between patient-generated and blinded
      provider-generated classifications of AF symptom severity was also assessed. The
      survey had good internal consistency (Cronbach alpha>0.82) and reproducibility
      (intraclass correlation coefficient=0.93). There was a good linear correlation
      with health-related quality-of-life aggregates measured by Pearson correlation
      coefficient (r=0.62 and 0.42 vs physical component summary and mental component
      summary, respectively). Compared with physical and mental component summary
      scores, the patient-generated symptom severity classification scheme showed
      robust discrimination between mild and moderate severity (p<0.0001 and p=0.0009)
      and between moderate and severe groups (p=0.0001 and p=0.012). In conclusion,
      this simple patient-generated AF classification scheme is robust, internally
      consistent, reproducible, and highly correlated with standardized quality-of-life
      measures.

PMID- 24878122
TI  - In-hospital and 12-month outcomes after acute coronary syndrome treatment in
      patients aged<40 years of age (from the Polish Registry of Acute Coronary
      Syndromes).
AB  - We aimed to compare the characteristics and in-hospital and 12-month outcomes in
      patients aged>40 and <40 years with acute coronary syndrome. The analysis
      involved 789 patients aged<40 years and 63,057 patients aged>=40 years enrolled
      in the ongoing Polish Registry of Acute Coronary Syndromes from October 2003 to
      December 2009. Patients aged<40 years with acute coronary syndrome differed from
      older patients in their clinical characteristics, treatment, and clinical
      outcome. The older patients more frequently had pulmonary edema (2.9% vs 0.4%,
      p<0.0001) and cardiogenic shock (4.7% vs 2.8%, p=0.011) on admission. For the
      younger patients, coronary angiography and percutaneous coronary intervention
      were performed more often (71.5% vs 60.5%, p<0.0001 and 51.5% vs 47.7%, p=0.04,
      respectively). The younger patients had a lower mortality rate than the older
      patients during hospitalization (1.5% vs 5.2%, p<0.0001) and during 12-month
      follow-up period (4.1% vs 13.4%, p<0.0001). Multivariate analysis revealed that
      age<40 years was one of the strongest factors associated with lower mortality
      during the 12 months after discharge (hazard ratio 0.42, 95% confidence interval
      0.29 to 0.62, p<0.0001). In conclusion, younger patients had more favorable in
      hospital and 1-year outcomes than older patients, and the age<40 years was
      revealed to be one of the strongest factors associated with lower mortality
      during the 1-year follow-up.

PMID- 24878123
TI  - Waist circumference as a vital sign in cardiology 20 years after its initial
      publication in the American Journal of Cardiology.
AB  - In 1994, we reported in The American Journal of Cardiology that a simple
      anthropometric measurement, waist circumference, was related to the amount of
      abdominal visceral adipose tissue measured by computed tomography. An elevated
      waist circumference was also found to be associated with several features of the
      cardiometabolic risk profile such as glucose intolerance, hyperinsulinemia, and
      an atherogenic dyslipidemic profile that included hypertriglyceridemia and
      reduced high-density lipoprotein cholesterol levels. Although a linear relation
      was found between waist circumference and these metabolic alterations, we
      reported that a waist circumference value of about 100 cm was associated with a
      high probability of finding diabetogenic and atherogenic abnormalities. The
      present short report provides a brief update of issues that have been raised
      regarding the measurement of waist circumference and its clinical use over a
      period of 20 years since the original publication. 

PMID- 24878124
TI  - Relation of smoking status to outcomes after cardiopulmonary resuscitation for in
      hospital cardiac arrest.
AB  - In-hospital cardiac arrest (IHCA) is common and is associated with poor
      prognosis. Data on the effect of smoking on outcomes after IHCA are limited. We
      analyzed the Nationwide Inpatient Sample databases from 2003 to 2011 for all
      patients aged>=18 years who underwent cardiopulmonary resuscitation (CPR) for
      IHCA to examine the differences in survival to hospital discharge and neurologic
      status between smokers and nonsmokers. Of the 838,464 patients with CPR for IHCA,
      116,569 patients (13.9%) were smokers. Smokers were more likely to be younger,
      Caucasian, and male. They had a greater prevalence of dyslipidemia, coronary
      artery disease, hypertension, chronic pulmonary disease, obesity, and peripheral
      vascular disease. Atrial fibrillation, heart failure, and diabetes mellitus with
      complications were less prevalent in smokers. Smokers were more likely to have a
      primary diagnosis of acute myocardial infarction (14.8% vs 9.1%, p<0.001) and
      ventricular tachycardia or ventricular fibrillation as the initial cardiac arrest
      rhythm (24.3% vs 20.5%, p<0.001). Smokers had a higher rate of survival to
      hospital discharge compared with nonsmokers (28.2% vs 24.1%, adjusted odds ratio
      1.06, 95% confidence interval 1.05 to 1.08, p<0.001). Smokers were less likely to
      have a poor neurologic status after IHCA compared with nonsmokers (3.5% vs 3.9%,
      adjusted odds ratio 0.92, 95% confidence interval 0.89 to 0.95, p<0.001). In
      conclusion, among patients aged >=18 years who underwent CPR for IHCA, we
      observed a higher rate of survival in smokers than nonsmokers-consistent with the
      "smoker's paradox." Smokers were also less likely to have a poor neurologic
      status after IHCA.

PMID- 24878125
TI  - Left ventricular dysfunction in duchenne muscular dystrophy and genotype.
AB  - Prognosis in patients with Duchenne muscular dystrophy (DMD) is guarded, and most
      deaths are due to cardiac or respiratory causes. It is unclear if some DMD gene
      mutations might be predictive of either mild or severe cardiac dysfunction. We
      studied 75 patients with DMD followed at our institution. Cardiac function, as
      assessed by yearly echocardiography, showed marked variability in left
      ventricular (LV) function. Some patients in their 3rd decade had no or minimal
      dysfunction, whereas others in their 2nd decade had very severe dysfunction.
      Therefore, 4 severity groups were defined ranging from no or mild LV dysfunction
      to severe LV dysfunction using patient age at first abnormal echocardiographic
      finding and degree of LV dysfunction. Genetic data were collected for all
      patients. Most patients had mutations from exon 1 to 20 to exon 41 to 55. The
      distribution of the 4 severity groups of LV dysfunction did not significantly
      differ between these 2 mutation groups. An analysis based on the number of exons
      involved (<5 vs >=5 exons) also found no significant difference in cardiac
      severity. When patients having identical mutations were compared with their
      cardiac course, concordance was often not evident. Steroid therapy had no
      apparent protection for the development of cardiomyopathy. In conclusion, 75
      patients with DMD showed marked variability in the severity of LV dysfunction.
      Neither the age of onset nor the severity of cardiomyopathy correlated with any
      of the mutation groups. 

PMID- 24878126
TI  - Relation of chronic obstructive pulmonary disease to atrial and ventricular
      arrhythmias.
AB  - Chronic obstructive pulmonary disease (COPD) is associated with increased
      cardiovascular morbidity and mortality, yet the exact pathophysiological links
      remain unclear. Whether the presence and severity of COPD are associated with
      atrial or ventricular arrhythmias recorded on continuous electrocardiographic
      monitoring is unknown. We identified consecutive adult patients who underwent
      clinically indicated pulmonary function testing as well as 24-hour Holter
      monitoring at the Mayo Clinic, Rochester, from 2000 to 2009. Demographic data and
      relevant co-morbidities were gathered from the electronic medical record;
      severity of COPD was classified according to the GOLD classification, and
      arrhythmias were classified in concordance with the current clinical guidelines.
      From 7,441 patients who were included (age 64+/-16 years, 49% woman, 92%
      Caucasian), COPD was diagnosed in 3,121 (41.9%). Compared with those without
      COPD, the presence and severity of COPD were associated with increased likelihood
      of atrial fibrillation/atrial flutter (AF/AFL; 23.3% vs 11.0%, respectively,
      p<0.0001), nonsustained ventricular tachycardia (NSVT; 13.0% vs 5.9%,
      respectively, p<0.0001), and sustained ventricular tachycardia (0.9% vs 1.6%,
      respectively, p<0.0001). COPD remained a significant predictor of AF/AFL and NSVT
      (p<0.0001 and p<0.0001, respectively) after adjusting for age, gender, tobacco
      use, obesity, hypertension, coronary artery disease, heart failure, diabetes,
      anemia, cancer, chronic kidney disease, and rate/rhythm control medications. In
      conclusion, the independent association between the presence and severity of COPD
      and arrhythmias (AF/AFL and NSVT) provides further insight into the markedly
      increased cardiovascular mortality of patients with COPD. Further studies should
      explore which anti-arrhythmic strategies would best apply to the patients with
      COPD.

PMID- 24878127
TI  - Comparison of 30-day and 5-year outcomes of percutaneous coronary intervention
      versus coronary artery bypass grafting in patients aged<=50 years (the Coronary
      aRtery diseAse in younG adultS Study).
AB  - Data on the outcome of young patients after coronary artery bypass grafting
      (CABG) and percutaneous coronary intervention (PCI) are scarce. Data on 2,209
      consecutive patients aged<=50 years who underwent CABG or PCI were
      retrospectively collected from 15 European institutions. PCI and CABG had similar
      30-day mortality rates (0.8% vs 1.4%, p=0.27), late survival (at 5 years, 97.8%
      vs 94.9%, p=0.082), and freedom from stroke (at 5 years, 98.0% and 98.0%,
      p=0.731). PCI was associated with significantly lower freedom from major adverse
      cardiac and cerebrovascular events (at 5 years, 73.9% vs 85.0%, p<0.0001), repeat
      revascularization (at 5 years, 77.6% vs 92.5%, p<0.0001), and myocardial
      infarction (at 5 years, 89.9% vs 96.6%, p<0.0001) compared with CABG. These
      findings were confirmed in propensity score-adjusted and matched analyses.
      Freedom from major adverse cardiac and cerebrovascular events after PCI was
      particularly low in diabetics (at 5 years, 58.0% vs 75.9%, p<0.0001) and in
      patients with multivessel disease (at 5 years, 63.6% vs 85.1%, p<0.0001). PCI in
      patients with ST elevation myocardial infarction was associated with
      significantly better 5-year survival (97.5% vs 88.8%, p=0.001), which was driven
      by its lower 30-day mortality rate (1.5% vs 6.0%, p=0.017). In conclusion,
      patients aged<=50 years have an excellent immediate outcome after either PCI or
      CABG with similar long-term survival when used according to the current clinical
      practice. PCI was associated with significantly lower freedom from myocardial
      infarction and repeat revascularization.

PMID- 24878128
TI  - Comparison of long-term postoperative sequelae in patients with tetralogy of
      Fallot versus isolated pulmonic stenosis.
AB  - Patients with tetralogy of Fallot (TOF) after complete repair and pulmonic
      stenosis (PS) after surgical valvotomy often develop significant pulmonic
      regurgitation (PR) that eventually requires valve replacement. Although criteria
      exist for the timing of pulmonary valve replacement in TOF, it remains less clear
      when to intervene in valvotomy patients and whether TOF recommendations can be
      applied. Our aim was to compare the structural and functional sequelae of
      valvotomy for PS with complete repair for TOF. We compared the clinical
      characteristics, electrocardiograms, echocardiograms, cardiac magnetic resonance
      imaging (MRI), and invasive hemodynamics of 109 adults (34 PS and 75 TOF) newly
      referred to a congenital heart disease center for evaluation of PR between 2005
      and 2012. Both cohorts were similar in terms of baseline demographics and
      presenting New York Heart Association function class. Valvotomy patients had a
      slightly greater degree of PR by echocardiogram, although it was similar by
      cardiac MRI. Electrocardiography QRS width was greater in patients with TOF
      (114+/-27 vs 150+/-28 ms, p<0.001). MRI right ventricular ejection fraction (49+/
      8 vs 41+/-11%, p=0.001) and left ventricular ejection fraction (59+/-7 vs 52+/
      10%, p=0.002) were lower in patients with TOF. Pacemaker or defibrillator
      implantation was significantly greater in patients with TOF (3% vs 23%, p=0.011).
      In conclusion, patients postvalvotomy and complete repair present with similar
      degrees of PR and severity of symptoms. Biventricular systolic function and
      electrocardiography QRS width appear less affected, suggesting morphologic
      changes in TOF and its repair that extend beyond the effects of PR. These
      findings suggest the need for developing disease-specific guidelines for patients
      with PR postvalvotomy.

PMID- 24878129
TI  - Utility of electrocardiogram in the assessment and monitoring of pulmonary
      hypertension (idiopathic or secondary to pulmonary developmental abnormalities)
      in patients<=18 years of age.
AB  - Electrocardiograms have utility in disease stratification and monitoring in adult
      pulmonary arterial hypertension (PAH). We examined the electrocardiographic
      findings that are common in pediatric PAH and assessed for correlation with
      disease severity and progression. We retrospectively identified patients aged<=18
      years followed at a single institution from January 2001 to June 2012 with
      catheterization-confirmed diagnosis of idiopathic PAH and PAH secondary to
      pulmonary developmental abnormalities. Patients with an electrocardiography
      performed within 60 days of catheterization were included. Primary and secondary
      outcomes are the prevalence of abnormal electrocardiographic findings at the time
      of catheterization and the association between electrocardiographic and
      hemodynamic findings and electrocardiographic changes with disease progression on
      follow-up catheterization, respectively. Of the 100 electrocardiography
      catheterization pairs derived from the 46 patients identified, 93% had an
      electrocardiographic abnormality: 78% had right ventricular hypertrophy (RVH) and
      52% had right axis deviation (RAD) for age. In patients with idiopathic PAH, the
      presence of RVH and RAD correlated with pulmonary vascular resistance and
      transpulmonary gradient. RAD and RVH on baseline electrocardiogram was associated
      with an increased risk of disease progression on subsequent catheterization (odds
      ratio 11.0, 95% confidence interval 1.3 to 96.2, p=0.03) after adjusting for PAH
      subgroup. The sensitivity, specificity, and positive and negative predictive
      values of RAD and RVH on baseline electrocardiogram for disease progression were
      92%, 48%, 33%, and 95%, respectively. In conclusion, electrocardiographic
      abnormalities are common in pediatric PAH. RAD and RVH on electrocardiogram were
      associated with worse hemodynamics, whereas their absence is suggestive of a lack
      of disease progression.

PMID- 24878130
TI  - Comparison of clinical features of left-sided infective endocarditis involving
      previously normal versus previously abnormal valves.
AB  - Native valve infective endocarditis (IE) in patients with normal valves has
      increased in the last decades. Whether patients with normal valves present a
      similar prognosis to those with pathologic valves is unresolved. Our aim is to
      describe epidemiologic and clinical differences between patients with left-sided
      IE and normal valves and those with native pathologic valves. We analyzed 945
      consecutive episodes of IE, 435 of which involved left-sided nonprosthetic IE.
      They were classified into 2 groups: episodes in normal valves (normal group,
      n=173) and episodes in pathologic valves (abnormal group, n=262). Patients in the
      normal group were younger, Staphylococcus aureus and Streptococcus bovis were
      more frequently isolated, and vegetations were more frequently found. Heart
      failure, septic shock, and the need for surgery or death were more common.
      Multivariate analysis identified the following as factors independently
      associated with normal valve IE: age<65 years, S bovis, S aureus, heart failure,
      and vegetation detection. Factors independently associated with in-hospital
      events included S aureus, periannular complications, heart failure, and septic
      shock development. In conclusion, compared with patients with abnormal valve IE,
      patients with IE on normal valves were younger, had a more virulent
      microbiological profile, developed heart failure and septic shock more
      frequently, needed more surgical procedures, and had worse prognosis.

PMID- 24878131
TI  - Jagat Narula, MD, PhD: A conversation with the editor.

PMID- 24878133
TI  - Eighth joint national committee: evidence versus eminence.

PMID- 24878132
TI  - Concerning antiplatelet therapy.

PMID- 24878134
TI  - Concerning antiplatelet therapy. Reply.

PMID- 24878135
TI  - Dabigatran in catheter ablation of atrial fibrillation: a call for a randomized
      control trial.

PMID- 24878136
TI  - The Bjork-Shiley convexo-concave heart valve experience from the perspective of
      the supervisory panel.

PMID- 24878137
TI  - The Bjork-Shiley convexo-concave heart valve experience from the perspective of
      the supervisory panel. Reply.

PMID- 24878138
TI  - Role of epicardial fat in atrial fibrillation after coronary artery bypass
      surgery.

PMID- 24878139
TI  - Flocculation and dewaterability of chemically enhanced primary treatment sludge
      by bioaugmentation with filamentous fungi.
AB  - In this study, filamentous fungal strains isolated from sewage sludge bioleached
      with iron-oxidizing bacteria were evaluated their effectiveness in improving the
      flocculation and dewaterability of chemically enhanced primary treatment (CEPT)
      sludge. Augmentation of the pre-grown mycelial biomass in the CEPT sludge had no
      significant changes in sludge pH but, improved sludge dewaterability, as
      evidenced from the decrease in capillary suction time. Improvement on sludge
      flocculation and dewaterability depended on the fungal strains, and a pellet
      forming Penicillium sp. was more effective than the fungal isolates producing
      filamentous form of mycelial biomass due to entrapment of sludge solids onto
      mycelial pellets. Fungal treatment also reduced the chemical oxygen demand of the
      CEPT sludge by 35-76%. Supplementation metal cations (Ca(2+), Mg(2+), and Fe(3+))
      to fungal pre-augmented sludge rapidly improved the sludge dewaterability. This
      study indicates that augmentation of selective fungal biomass can be a potential
      method for CEPT sludge flocculation and dewaterability. 

PMID- 24878140
TI  - Identification and differentiation of food-related bacteria: A comparison of FTIR
      spectroscopy and MALDI-TOF mass spectrometry.
AB  - The food industry requires easy, accurate, and cost-effective techniques for
      microbial identification to ensure safe products and identify microbial
      contaminations. In this work, FTIR spectroscopy and MALDI-TOF mass spectrometry
      were assessed for their suitability and applicability for routine microbial
      diagnostics of food-related microorganisms by analyzing their robustness
      according to changes in incubation time and medium, identification accuracy and
      their ability to differentiate isolates down to the strain level. Changes in the
      protocol lead to a significantly impaired performance of FTIR spectroscopy,
      whereas they had only little effects on MALDI-TOF MS. Identification accuracy was
      tested using 174 food-related bacteria (93 species) from an in-house strain
      collection and 40 fresh isolates from routine food analyses. For MALDI-TOF MS,
      weaknesses in the identification of bacilli and pseudomonads were observed; FTIR
      spectroscopy had most difficulties in identifying pseudomonads and
      enterobacteria. In general, MALDI-TOF MS obtained better results (52-85% correct
      at species level), since the analysis of mainly ribosomal proteins is more robust
      and seems to be more reliable. FTIR spectroscopy suffers from the fact that it
      generates a whole-cell fingerprint and intraspecies diversity may lead to
      overlapping species borders which complicates identification. In the present
      study values between 56% and 67% correct species identification were obtained. On
      the opposite, this high sensitivity offers the opportunity of typing below the
      species level which was not possible using MALDI-TOF MS. Using fresh isolates
      from routine diagnostics, both techniques performed well with 88% (MALDI-TOF) and
      75% (FTIR) correct identifications at species level, respectively. 

PMID- 24878142
TI  - Women's perceptions of everyday occupations: outcomes of the Redesigning Daily
      Occupations (ReDO) programme.
AB  - AIMS: The aim was to (i) assess the outcomes of the 16-week Redesigning Daily
      Occupations (ReDO) programme for women on sick leave due to stress-related
      disorders, in terms of occupational value, satisfaction with everyday
      occupations, and participation level; (ii) investigate the relationships between
      those outcomes and return-to-work rate. METHODS: A total of 42 women receiving
      ReDO and 42 receiving care as usual (CAU) were included in a matched-control
      study with measurements before and after the rehabilitation. Seventy-eight
      participated on both occasions. They completed self-report questionnaires
      regarding the aforementioned outcomes. Return-to-work data were obtained from the
      registers of the Social Insurance Offices. RESULTS: Increases in concrete,
      symbolic, and self-reward values were found in both groups, but no statistically
      significant difference between the groups was demonstrated. The ReDO group
      improved more than the CAU group, however, on satisfaction with everyday
      occupations and participation level. Occupational value, but not satisfaction
      with everyday occupations, was related to return to work. CONCLUSIONS: Everyday
      occupations were shown to be relevant outcomes after work rehabilitation. They
      could play an important role in future development of profession-specific
      evidence of occupational therapy. Further support was obtained for viewing
      occupational value and satisfaction with everyday occupations as theoretically
      distinct phenomena.

PMID- 24878141
TI  - Mutans streptococci enumeration and genotype selection using different bacitracin
      containing media.
AB  - The primary etiological agents associated with dental caries include the mutans
      streptococci (MS) comprised of Streptococcus mutans and Streptococcus sobrinus.
      The effective cultivation and isolation of MS are necessary for the study of MS,
      including their proper clinical assessment in the epidemiological study of dental
      caries. Several selective media have been developed for the isolation,
      enumeration, and characterization of MS. However, inhibition of MS may occur,
      reducing counts and perhaps limiting selection of some strains. The purpose of
      this study was to compare five culture media containing bacitracin recommended
      for the isolation of MS. Five commonly used bacitracin-containing media (MSB,
      MSKB, GTSB, TYS20B, and TYCSB) used for MS isolation were quantitatively
      evaluated. Standard plate counts were performed in duplicate for 2 prototype MS
      strains (S. mutans UA159 and S. sobrinus 6715) and for MS isolates from clinical
      saliva samples obtained from 16 children (approximate age 5years) to determine
      total plate counts, and total S. mutans counts. Selected isolates (n=249) from
      all five media for 5 saliva samples were further confirmed as S. mutans with real
      time PCR then subsequently evaluated qualitatively with rep-PCR for genotype
      determination. All media resulted in variable enumeration with no significant
      difference in MS counts. MS prototype strains grew well on all five media;
      clinical isolates demonstrated more variability in counts but no overall
      significant differences were found. MSB demonstrated comparable ability to grow
      S. mutans but allowed for more non-S. mutans growth. All 5 media identified a
      consistent predominant genotype by rep-PCR. Recovery of minor genotypes was not
      inhibited by media type. 

PMID- 24878143
TI  - Elevated CO2 causes changes in the photosynthetic apparatus of a toxic
      cyanobacterium, Cylindrospermopsis raciborskii.
AB  - We studied the physiological acclimation of growth, photosynthesis and CO2
      concentrating mechanism (CCM) in Cylindrospermopsis raciborskii exposed to low
      (present day; L-CO2) and high (1300ppm; H-CO2) pCO2. Results showed that under H
      CO2 the cell specific division rate (MUc) was higher and the CO2- and light
      saturated photosynthetic rates (Vmax and Pmax) doubled. The cells' photosynthetic
      affinity for CO2 (K0.5CO2) was halved compared to L-CO2 cultures. However, no
      significant differences were found in dark respiration rates (Rd), pigment
      composition and light harvesting efficiency (alpha). In H-CO2 cells, non
      photochemical quenching (NPQ), associated with state transitions of the electron
      transport chain (ETC), was negligible. Simultaneously, a reorganisation of PSII
      features including antenna connectivity (JconPSIIalpha), heterogeneity
      (PSIIalpha/beta) and effective absorption cross sectional area
      (sigmaPSIIalpha/beta) was observed. In relation to different activities of the
      CCM, our findings suggest that for cells grown under H-CO2: (1) there is down
      regulation of CCM activity; (2) the ability of cells to use the harvested light
      energy is altered; (3) the occurrence of state transitions is likely to be
      associated with changes of electron flow (cyclic vs linear) through the ETC; (4)
      changes in PSII characteristics are important in regulating state transitions. 

PMID- 24878144
TI  - Cancer therapy combining high-intensity focused ultrasound and megavoltage
      radiation.

PMID- 24878145
TI  - Managing pressure: patterns of appraisals and coping strategies of non-elite and
      elite athletes during competition.
AB  - The purpose of this study was to compare moment-to-moment appraisals and coping
      strategies of 4 non-elite and 2 elite male trap shooters during competitions and
      in particular during periods of competition perceived as critical to performance.
      Appraisals and coping patterns of trap shooters were captured via verbal reports
      of thinking provided between sets of shots during major competitions. Verbal
      reports were coded according to an appraisal and coping typology. Coded data as
      well as shooting performance data were subjected to a sequential analysis of
      probabilities of pairs of events. Fewer reports of negative appraisals (NEGAs)
      and more frequent reports of problem-focused coping (PFC) were observed among
      both elite athletes compared to non-elite athletes. After making a NEGA, non
      elite shooters often progressed to the next target without attempting to cope,
      whereas elite shooters used both PFC and emotion-focused coping (EFC) before
      proceeding to the next target. After missing a target, the non-elite athletes
      used more EFC than expected. These results indicate that elite athletes are more
      likely to cope with NEGAs than non-elite athletes using a wider variety of coping
      strategies. Athletes might benefit from increased awareness of the potentially
      detrimental impact of NEGAs on performance and by integrating coping strategies
      within preparatory routines.

PMID- 24878146
TI  - [Stroke in atrial fibrillation patients already on oral anticoagulant: What more
      can be done?].
AB  - Oral anticoagulants dramatically reduce the risk of embolic stroke in patients
      with atrial fibrillation (AF). However, each year, 1 to 3 % of patients will
      present an ischemic stroke despite being on oral anticoagulant. These events can
      result from efficacy fluctuations, non-cardioembolic stroke, or insufficient
      efficacy despite appropriate anticoagulation. There are several therapeutic
      options depending on presumed mechanism of ischemic stroke. However, none of
      these options has been specifically evaluated in appropriate studies. These
      options include: reinforcement of education or change in VKA drugs in case of
      documented therapeutic fluctuations, adjunction of aspirin, change to direct oral
      anticoagulants, or percutaneous left-appendage closure. 

PMID- 24878147
TI  - Complete androgen sensitivity syndrome.

PMID- 24878148
TI  - Control of C4a-hydroperoxyflavin protonation in the oxygenase component of p
      hydroxyphenylacetate-3-hydroxylase.
AB  - The protonation status of the peroxide moiety in C4a-(hydro)peroxyflavin of p
      hydroxyphenylacetate-3-hydroxylase can be directly monitored using transient
      kinetics. The pKa for the wild-type (WT) enzyme is 9.8 +/- 0.2, while the values
      for the H396N, H396V, and H396A variants are 9.3 +/- 0.1, 7.3 +/- 0.2, and 7.1 +/
      0.2, respectively. The hydroxylation efficiency of these mutants is lower than
      that of the WT enzyme. Solvent kinetic isotope effect studies indicate that
      proton transfer is not the rate-limiting step in the formation of C4a-OOH. All
      data suggest that His396 may act as an instantaneous proton provider for the
      proton-coupled electron transfer that occurs before the transition state of C4a
      OOH formation. 

PMID- 24878149
TI  - Propofol prevents lung injury after intestinal ischemia-reperfusion by inhibiting
      the interaction between mast cell activation and oxidative stress.
AB  - AIMS: Both mast cells and oxidative stress are involved in acute lung injury
      (ALI) induced by intestinal ischemia-reperfusion (IIR). The aim of this study was
      to investigate whether propofol could improve IIR-induced ALI through inhibiting
      their interaction. MAIN METHODS: Repetitive, brief IIR or IIR+compound 48/80 was
      performed in adult Sprague-Dawley rats pretreated with saline, apocynin or
      propofol. And their lungs were excised for histology, ELISA and protein
      expression measurements 2h after reperfusion. KEY FINDINGS: Rats pretreated with
      saline developed critical ALI 2h after IIR. We found significant elevations in
      lung injury scores, lung wet/dry ratio and gp91phox, p47phox, intercellular cell
      adhesion molecule-1 protein expressions and higher level of malondialdehyde,
      interleukin-6 contents, and myeloperoxidase activities, as well as significant
      reductions in superoxide dismutase activities, accompanied with increases in mast
      cell degranulation evidenced by significant increases in mast cell counts, beta
      hexosaminidase concentrations, and tryptase expression. And the lung injury was
      aggravated in the presence of compound 48/80. However, pretreated with propofol
      and apocynin not only ameliorated the IIR-mediated pulmonary changes beyond the
      biochemical changes but also reversed the changes that were aggravated by
      compound 48/80. SIGNIFICANCE: Propofol protects against IIR-mediated ALI, most
      likely by inhibiting the interaction between oxidative stress and mast cell
      degranulation.

PMID- 24878151
TI  - Transitioning nutrition education programming delivery to online formats.

PMID- 24878150
TI  - Implementing a multicomponent school-based obesity prevention intervention: a
      qualitative study.
AB  - OBJECTIVE: To explore barriers and facilitators to implementing and sustaining
      Healthy Choices, a 3-year multicomponent obesity prevention intervention
      implemented in middle schools in Massachusetts. METHODS: Using purposive
      sampling, 56 in-depth interviews were conducted with middle school employees
      representing different positions (administrators, teachers, food service
      personnel, and employees serving as intervention coordinators). Interviews were
      recorded and transcribed. Emergent themes were identified using thematic
      analyses. RESULTS: State-mandated testing, budget limitations, and time
      constraints were viewed as implementation barriers, whereas staff buy-in,
      external support, and technical assistance were seen as facilitating
      implementation. Respondents thought that intervention sustainability depended on
      external funding and expert assistance. CONCLUSIONS AND IMPLICATIONS: Results
      confirm the importance of gaining faculty and staff support. Schools implementing
      large-scale interventions should consider developing sustainable partnerships
      with organizations that can provide resources and ongoing training.
      Sustainability of complex interventions may depend on state-level strategies that
      provide resources for implementation and technical assistance.

PMID- 24878153
TI  - [COPD screening and COPD early diagnosis].

PMID- 24878152
TI  - Local news media framing of obesity in the context of a sugar-sweetened beverage
      reduction media campaign.
AB  - OBJECTIVE: This study examined local news media's framing of obesity preceding
      and surrounding the Philadelphia sugar-sweetened beverage reduction media
      campaign. METHODS: Using key search terms pertaining to obesity and sugary
      beverages, the authors searched the LexisNexis database and gathered local news
      stories (n = 167) that were aired or published between October, 2010 and March,
      2011. They conducted a content analysis, coding for framing-related outcome
      measures (underlying factors, action steps, and contextual agents). RESULTS:
      Overall, the news media employed individual-level framing in the majority of
      stories when discussing obesity, both before and after the campaign launch. After
      the campaign launched, however, stories were significantly more likely to mention
      systemic-level contextual agents such as food companies (P = .008), beverage
      companies (P = .03), and champions or advocates (P = .001). CONCLUSIONS AND
      IMPLICATIONS: The researchers observed a shift in the local news media discourse
      toward more thematic framing of obesity, and suggest that public health officials
      consider the potential impact of news media frames on garnering public support
      for future policy implementations.

PMID- 24878154
TI  - [Second medical opinions in the era of multidisciplinary coordination meetings].

PMID- 24878156
TI  - [Need for the training of GPs to perform spirometry: a study of French GP
      trainees].
AB  - INTRODUCTION: The increased prevalence of asthma and COPD, the expected decline
      in the number of respiratory physicians and the availability of spirometers in
      primary care suggest that GPs should perform spirometry. OBJECTIVE: To evaluate
      French final year medical (GP) students' theoretical and practical knowledge of
      spirometry. METHODS: The students completed a questionnaire and were then
      separated into 4 groups: satisfactory theoretical and practical knowledge (group
      1), theoretical knowledge (group 2), practical knowledge (group 3), insufficient
      theoretical and practical knowledge (group 4). RESULTS: One thousand two hundred
      and sixty one students (29 universities) were included between February and April
      2012. Of the students, 4.3 % (54) fell into group 1, 35.2% (444) into group 2,
      5.4% (68) into group 3 and 63.7% (803) into group 4. The students in group 1 had
      done significantly more internships in departments of respiratory medicine during
      their training (P<0.0001, OR: 3.93, IC95%: 2.2-7.07). CONCLUSION: As a result of
      their theoretical and practical training, only 5% of the students considered
      themselves able to perform and interpret spirometry. A specific training program
      is necessary.

PMID- 24878155
TI  - [Screening for chronic obstructive pulmonary disease by electronic mini
      spirometry in general practice].
AB  - INTRODUCTION: Screening for COPD is currently considered to be insufficient.
      Electronic mini-spirometers allow screening for COPD in general practice.
      OBJECTIVES: To assess the prevalence of COPD in a population of at-risk patients
      in general practice (GP) and to identify the high-risk factors for the disease.
      METHODS: A cross-sectional study was performed in a GP setting. Patients aged
      between 40 and 75years with a history of smoking, occupational exposure to toxic
      substances or chronic respiratory symptoms were offered airflow assessments by
      electronic mini-spirometry. For any value of FEV1/FEV6 less than 70 %, screening
      for COPD was considered as positive. RESULTS: Of the 778 patients seen during
      routine consultations, 273 (35.1 %) fulfilled the inclusion criteria. The test
      was positive in 128 of the eligible patients (46.9 %). The prevalence of proven
      COPD (ratio<70 %) was 13.9 % (38 patients). The high-risk factors were age over
      60years (P=0.03), body mass index over 28 (P=0.04), smoking history of more than
      30pack-years (P<0.0001), presence of clinical signs (P<0.0001) and industrial
      exposure to toxic substances (P=0.03). CONCLUSIONS: Targeted screening of
      patients with risk factors for COPD can be performed in a GP setting. An
      electronic mini-spirometer is a reliable and inexpensive screening tool.

PMID- 24878157
TI  - [Evaluation of requests for a second medical opinion by patients with lung
      cancer].
AB  - INTRODUCTION: Getting a second opinion seems common in oncology, even though the
      management of these serious diseases results from a multidisciplinary approach.
      Our aim was to determine the incidence of requests for a second opinion in
      thoracic oncology at the university hospital of Nancy, since the establishment of
      the Cancer Plan in 2003. This plan formalized multidisciplinary staff meetings,
      which should help to reassure patients and therefore reduce the recourse to
      additional consultations. METHODS: A detailed and anonymous questionnaire was
      conducted on 77 patients suffering from lung cancer, followed-up over 2years in
      the respiratory department of the University Hospital of Nancy. The socio
      economic characteristics were collected from the medical records. RESULTS:
      Recourse to a second practitioner was reported by 14 % of the patients suffering
      from lung cancer. It concerned more women than men and more patients with a
      higher educational level and socio-professional category. CONCLUSION: Requests
      for a second opinion by patients with lung cancer are not as frequent as
      expected. However, when they are made, it is more frequently by women and
      patients with a higher socio-economic status.

PMID- 24878158
TI  - [Long-term oxygen therapy in France, 2006-2011].
AB  - OBJECTIVE: The study aimed to describe the main characteristics of people treated
      with long-term oxygen therapy (LTOT) and the trends between 2006 and 2011 for
      prevalence and incidence. METHODS: Data were provided from a sample comprising
      1/97 of the permanent beneficiaries of the French health insurance. The sample
      contains anonymous socio-demographic characteristics and data on health care
      reimbursements. The analyses were carried out among adults aged 20 years and
      above who had received benefits on account of LTOT. RESULTS: In 2011, 2.6% of
      adults were treated with LTOT, corresponding to around 135,000 people. The crude
      incidence rate was 0.90/00. The prescription of LTOT included LTOT alone (70%),
      LTOT associated with assisted ventilation (23%) and LTOT associated with
      continuous positive airway pressure (7%). About 45% of the patients were
      supported financially in the long-term illness program of the French Social
      Security because of severe chronic respiratory failure. Between 2006 and 2011,
      the age-adjusted prevalence rates increased by 2.9% per year in men and by 6.7%
      per year in women. The age-adjusted incidence rates remained stable in men (+1.6%
      per year, P=0.45) but increased in women (+4.7% per year, P=0.04). The median
      survival was 27 months. CONCLUSION: This analysis of the data demonstrates an
      increasing burden associated with LTOT in France from 2006 to 2011.

PMID- 24878159
TI  - [Hydroxyurea-induced pneumonia].
AB  - INTRODUCTION: Hydroxyurea is an antimetabolite drug used in the treatment of
      myeloproliferative disorders. Common adverse effects include haematological,
      gastrointestinal cutaneous manifestations, and fever. Hydroxyurea-induced
      pneumonitis is unusual. CASE REPORT: A female patient was treated with
      hydroxyurea for polycythemia vera. She was admitted 20 days after commencing
      treatment with a high fever, productive cough, clear sputum and nausea. A chest
      CT-scan showed diffuse ground-glass opacities. Microbiological investigations
      were negative. The symptoms disappeared a few days after discontinuation of the
      drug and rechallenge led to a relapse of symptoms. CONCLUSION: Our case and 15
      earlier cases of hydroxyurea-induced pneumonitis are reviewed. Two patterns of
      this disease may exist: an acute febrile form occurring within 1 month of
      introduction of hydroxyurea and a subacute form without fever. Even if uncommon,
      one should be aware of this complication of hydroxyurea.

PMID- 24878160
TI  - [Severe pneumonia due to cytomegalovirus in chronic obstructive pulmonary
      disease].
AB  - Severe pneumonia due to cytomegalovirus in chronic obstructive pulmonary disease.
      INTRODUCTION: We describe two cases of immunocompetent patients with chronic
      obstructive pulmonary disease (COPD) who developed severe cytomegalovirus (CMV)
      pneumonia. The clinical and radiological context and CMV replication in broncho
      alveolar lavage suggested a diagnosis of CMV pneumonia. CASE HISTORIES: We report
      two cases in patients with moderate chronic obstructive pulmonary disease not
      treated with long-term steroid therapy who developed bilateral pneumonia with
      hypoxaemia. The only pathogen identified was CMV with replication of the virus in
      the broncho-alveolar lavage. Investigation failed to detect any associated immune
      deficiency. CONCLUSION: Severe cytomegalovirus pneumonia could be encouraged by
      the existence of chronic obstructive pulmonary disease due to local inflammatory
      changes.

PMID- 24878161
TI  - [Intrapericardial lung cancer metastases: Is a curative approach feasible?].
AB  - INTRODUCTION: Lung cancer metastases are classified M1a and M1b. Studies on
      patients with pleural invasion graded M1a have demonstrated the possibility of
      prolonged survival following multimodality treatment, but this has not been
      reported for M1a pericardial involvement. CASE REPORT: A 59-year-old man
      underwent lung surgery for a poorly differentiated adenocarcinoma TTF1+ with K
      ras mutation. He was staged as pT4N0 because of a nodule in another ipsilateral
      lobe. A pericardial effusion with imminent tamponade occurred during the
      postoperative course necessitating drainage leading to the discovery of
      pericardial metastases and restaging as pT4N0M1a. Adjuvant treatment was
      performed and the patient remains alive and disease free 3 years later.
      CONCLUSIONS: Management of pericardial M1a might be refined as has been the case
      in pleural M1a disease. Biological data might allow more precise classification
      and treatment. N0-N1 and non-T3-T4 by invasion patients might in selected cases
      benefit from surgery included as part of multimodal therapy.

PMID- 24878162
TI  - [Pleuropericardial cyst rupturing into the pericardium causing tamponade].
AB  - Pleuropericardial cysts of the mediastinum are rare lesions, usually congenital
      but exceptionally acquired. They are often asymptomatic, but complications can
      occur. We report below the case of a 35-year-old man who presented with an
      acquired right-sided para-tracheal mesothelial cyst that ruptured into the
      pericardium and was responsible for clinical tamponade. Although the majority of
      mesothelial cysts are asymptomatic, only a strict clinical and radiological
      follow-up can provide an indication for surgical resection. This should be
      reserved for symptomatic patients or for those facing an uncertain diagnosis. 

PMID- 24878163
TI  - [American histoplasmosis: clinicopathological features in immunocompetent and
      immunocompromised patients. A report of two cases of infection by Histoplasma
      capsulatum on Reunion Island].
AB  - INTRODUCTION: Histoplasmosis is a fungal infection caused by Histoplasma
      capsulatum var. capsulatum. It shows pulmonary or multivisceral involvement.
      Infective spores are inhaled from soils that contain bat or bird guano. The
      clinical picture depends on the intensity of the exposure and the immune status
      of the host. CASE REPORTS: We report two cases of histoplasmosis that reflect its
      variability in clinical and histopathological expression: a pseudo-tumoral
      nodular form or histoplasmoma in a pauci-symptomatic immunocompetent patient and
      a disseminated form with severe respiratory and mucocutaneous involvement in an
      immunocompromised patient. The histoplasmoma presented as a spiculated,
      hypermetabolic, solitary pulmonary nodule. Histopathological examination showed
      well-formed epithelioid granulomas with caseous central necrosis containing
      numerous histoplasma yeasts. In the patient with disseminated infection, the
      diagnosis was confirmed by seeing yeast forms in bronchoalveolar lavage fluid and
      skin biopsy. CONCLUSIONS: These patients are the second and third cases of
      histoplasmosis reported on Reunion Island. Both had traveled in endemic areas
      several years previously. The most likely pathophysiological mechanism is the
      reactivation of an old latent infection. There is, therefore, no argument at
      present in favor of the presence of contaminated soils on Reunion Island.

PMID- 24878165
TI  - Autocatalytic isomerizations of the two most stable conformers of carbonic acid
      in vapor phase: double hydrogen transfer in carbonic acid homodimers.
AB  - The cis-cis [(cc)] and cis-trans [(ct)] conformers of carbonic acid (H2CO3) are
      known as the two most stable conformers based on the different orientations of
      two OH functional groups present in the molecule. To explain the interconversion
      of the (cc)-conformer to its (ct)-conformer, the rotation of one of the two
      indistinguishable OH functional groups present in the (cc)-conformer has been
      shown until now as the effective isomerization mechanism. Moreover, the (ct)
      conformer, which is slightly energetically disfavored over the (cc)-conformer,
      has been considered as the starting point for the decomposition of H2CO3 into CO2
      and H2O molecules. Experimentally, on the other hand, the infrared (IR) and Raman
      spectroscopy of the crystalline H2CO3 polymorphs suggest that the most possible
      basic building blocks of H2CO3 polymorphs consist of only and exclusively the
      (cc)-conformers. However, the sublimations of these crystalline H2CO3 polymorphs
      result both the (cc)- and (ct)-conformers in the vapor phase with the (cc)
      conformer being the major species. In this article, we first report the high
      level ab initio calculations investigating the energetics of the autocatlytic
      isomerization mechanism between the two most stable conformers of carbonic acid
      in the vapor phase. The calculations have been performed at the MP2 level of
      theory in conjunction with aug-cc-pVDZ, aug-cc-pVTZ, and 6-311++G(3df,3pd) basis
      sets. The results of the present study specifically and strongly suggest that
      double hydrogen transfer within the eight-membered cyclic doubly hydrogen-bonded
      (H-bonded) ring interface of the H2CO3 homodimer formed between two (cc)
      conformers is ultimately the starting mechanism for the isomerization of the (cc)
      conformer to its (ct)-conformer, especially, during the sublimation of the H2CO3
      polymorphs, which result in the vapor phase concentration of the (cc)-conformer
      at the highest levels. 

PMID- 24878164
TI  - [Evaluation of a manual CPAP home telemonitoring device to an automatic one].

PMID- 24878166
TI  - Survey of HIV care providers on management of HIV serodiscordant couples -
      assessment of attitudes, knowledge, and practices.
AB  - Human immunodeficiency virus (HIV) serodiscordant couples are at risk of sexual
      transmission of HIV between the infected and uninfected partner. We assessed New
      York area care providers for people living with HIV regarding attitudes,
      knowledge, and practice patterns toward fertility and conception in
      serodiscordant couples. Data were collected via a survey distributed in October
      2013. Seventeen percent of respondents reported prescribing antiretroviral
      preexposure prophylaxis (PrEP) for a woman in a serodiscordant couple, and 38%
      percent of respondents reported having counseled serodiscordant couples on timed,
      unprotected intercourse without PrEP. Respondents who reported being "very"
      familiar with the data on HIV transmission in serodiscordant couples were more
      likely to report counseling their patients in timed, unprotected intercourse
      compared with those who reported less familiarity with the data (41% vs. 8%, p =
      0.001). Although only 20% reported being "very" or "somewhat" familiar with the
      data on the safety of sperm washing with intrauterine insemination, those who did
      were more likely to have reported referring a patient for assisted reproductive
      technology (61% vs. 32%, p = 0.006). Effective patient counseling and referral
      for appropriate reproductive options were associated with knowledge of the
      literature pertaining to these options. This emphasizes the need for further
      provider education on reproductive options and appropriate counseling for
      serodiscordant couples. 

PMID- 24878167
TI  - Protein folding dynamics in the cell.
AB  - Protein folding is a remarkably fast unimolecular reaction, spanning microseconds
      to hours at room temperature. Thus, free energy differences and activation
      barriers on the free energy landscape of proteins are rather small. This opens up
      the possibility of living cells modulating their protein's landscapes, providing
      cells another way to control the function of their proteomes after
      transcriptional control, translational control, and post-translational
      modification. In this Feature Article, we discuss advances in physicochemical
      studies of protein stability and folding inside living cells. We focus in
      particular on our studies using fast relaxation imaging (FREI). Although the
      effect of the cell on protein free energy landscapes is only a few kT, the strong
      cooperativity of many folding and binding processes allows small modulation of
      the energy and entropy to produce a large population modulation. Lastly, we
      discuss some biomolecular processes that are particularly likely to be affected
      by in-cell modulation of the proteome, and thus of interest for quantitative
      physical chemistry studies. 

PMID- 24878168
TI  - Variation in embryonic mortality and maternal transcript expression among
      Atlantic cod (Gadus morhua) broodstock: a functional genomics study.
AB  - Early life stage mortality is an important issue for Atlantic cod aquaculture,
      yet the impact of the cod maternal (egg) transcriptome on egg quality and
      mortality during embryonic development is poorly understood. In the present work,
      we studied embryonic mortality and maternal transcript expression using eggs from
      15 females. Total mortality at 7days post-fertilization (7 dpf, segmentation
      stage) was used as an indice of egg quality. A 20,000 probe (20K) microarray
      experiment compared the 7hours post-fertilization (7 hpf, ~2-cell stage) egg
      transcriptome of the two lowest quality females (>90% mortality at 7 dpf) to that
      of the highest quality female (~16% mortality at 7 dpf). Forty-three microarray
      probes were consistently differentially expressed in both low versus high quality
      egg comparisons (25 higher expressed in low quality eggs, and 18 higher expressed
      in high quality eggs). The microarray experiment also identified many immune
      relevant genes [e.g. interferon (IFN) pathway genes ifngr1 and ifrd1)] that were
      highly expressed in eggs of all 3 females regardless of quality. Twelve of the 43
      candidate egg quality-associated genes, and ifngr1, ifrd1 and irf7, were included
      in a qPCR study with 7 hpf eggs from all 15 females. Then, the genes that were
      confirmed by qPCR to be greater than 2-fold differentially expressed between 7
      hpf eggs from the lowest and highest quality females (dcbld1, ddc, and acy3 more
      highly expressed in the 2 lowest quality females; kpna7 and hacd1 more highly
      expressed in the highest quality female), and the 3 IFN pathway genes, were
      included in a second qPCR study with unfertilized eggs. While some maternal
      transcripts included in these qPCR studies were associated with extremes in egg
      quality, there was little correlation between egg quality and gene expression
      when all females were considered. Both dcbld1 and ddc showed greater than 100
      fold differences in transcript expression between females and were potentially
      influenced by family. The Atlantic cod ddc (dopa decarboxylase) complete cDNA was
      characterized, and has a 1461bp open reading frame encoding a 486 amino acid
      protein that contains all eight residues of the conserved pyridoxal 5'-phosphate
      binding site including the catalytic lysine. This study provides valuable new
      information and resources related to the Atlantic cod egg transcriptome. Some of
      these microarray-identified, qPCR-confirmed, Atlantic cod egg transcripts (e.g.
      ddc, kpna7) play important roles during embryonic development of other vertebrate
      species, and may have similar functions in Atlantic cod. 

PMID- 24878169
TI  - Isolation and characterization of novel microsatellite markers for the northern
      mauxia shrimp, Acetes chinensis, using pyrosequencing.
AB  - Among the 14 species in the Acetes genus, Acetes japonicus and Acetes chinensis,
      are the only and also abundant two species around the Korean Peninsula, and are
      used in traditional recipes. These species are of great economic importance, but
      little is known about their population genetics, despite the fact that
      information of this kind is important for stock assessment, fisheries management
      and identification of origin. A total of 9 microsatellite (MS) markers for A.
      chinensis were developed using pyrosequencing techniques. Polymorphisms of these
      markers were evaluated in 96 wild individuals collected from the Yellow Sea off
      the coast of Korea. A total of 133 alleles were detected at nine loci, with a
      cross-species transferability of 56% with A. japonicus. These markers will
      facilitate assessment of population genetic diversity in the genus Acetes. 

PMID- 24878170
TI  - Effect of maternal immune activation on the kynurenine pathway in preadolescent
      rat offspring and on MK801-induced hyperlocomotion in adulthood: amelioration by
      COX-2 inhibition.
AB  - Infections during pregnancy and subsequent maternal immune activation (MIA)
      increase risk for schizophrenia in offspring. The progeny of rodents injected
      with the viral infection mimic polyI:C during gestation display brain and
      behavioural abnormalities but the underlying mechanisms are unknown. Since the
      blood kynurenine pathway (KP) of tryptophan degradation impacts brain function
      and is strongly regulated by the immune system, we tested if KP changes occur in
      polyI:C offspring at preadolescence. We also tested whether MK801-induced
      hyperlocomotion, a behaviour characteristic of adult polyI:C offspring, is
      prevented by adolescent treatment with celecoxib, a COX-2 inhibitor that impacts
      the KP. Pregnant rats were treated with polyI:C (4mg/kg, i.v.) or vehicle on
      gestational day 19. Serum levels of KP metabolites were measured in offspring of
      polyI:C or vehicle treated dams at postnatal day (PND) 31-33 using HPLC/GCMS.
      Additional polyI:C or vehicle exposed offspring were given celecoxib or vehicle
      between PND 35 and 46 and tested with MK801 (0.3mg/kg) in adulthood (PND>90).
      Prenatal polyI:C resulted in increases in the serum KP neurotoxic metabolite
      quinolinic acid at PND 31-33 (105%, p=0.014). In contrast, the neuroprotective
      kynurenic acid and its precursor kynurenine were significantly decreased (28%
      p=0.027, and 31% p=0.033, respectively). Picolinic acid, another neuroprotective
      KP metabolite, was increased (31%, p=0.014). Adolescent treatment with celecoxib
      (2.5 and 5mg/kg/day, i.p.) prevented the development of MK801-induced
      hyperlocomotion in adult polyI:C offspring. Our study reveals the blood KP as a
      potential mechanism by which MIA interferes with postnatal brain maturation and
      associated behavioural disturbances and emphasises the preventative potential of
      inflammation targeting drugs. 

PMID- 24878171
TI  - Acute sleep deprivation in healthy young men: impact on population diversity and
      function of circulating neutrophils.
AB  - Lack of sleep greatly affects our immune system. The present study investigates
      the acute effects of total sleep deprivation on blood neutrophils, the most
      abundant immune cell in our circulation and the first cell type recruited to
      sites of infection. Thus, the population diversity and function of circulating
      neutrophils were compared in healthy young men following one night of total sleep
      deprivation (TSD) or after 8h regular sleep. We found that neutrophil counts were
      elevated after nocturnal wakefulness (2.0 +/- 0.2 * 10(9)/l vs. 2.6 +/- 0.2 *
      10(9)/l, sleep vs. TSD, respectively) and the population contained more immature
      CD16(dim)/CD62L(bright) cells (0.11 +/- 0.040 * 10(9)/l [5.5 +/- 1.1%] vs. 0.26
      +/- 0.020 * 10(9)/l [9.9 +/- 1.4%]). As the rise in numbers of circulating mature
      CD16(bright)/CD62L(bright) neutrophils was less pronounced, the fraction of this
      subpopulation showed a significant decrease (1.8 +/- 0.15 * 10(9)/l [88 +/- 1.8%]
      vs. 2.1 +/- 0.12 * 10(9)/l [82 +/- 2.8%]). The surface expression of receptors
      regulating mobilization of neutrophils from bone marrow was decreased (CXCR4 and
      CD49d on immature neutrophils; CXCR2 on mature neutrophils). The receptor CXCR2
      is also involved in the production of reactive oxygen species (ROS), and in line
      with this, total neutrophils produced less ROS. In addition, following sleep
      loss, circulating neutrophils exhibited enhanced surface levels of CD11b, which
      indicates enhanced granular fusion and concomitant protein translocation to the
      membrane. Our findings demonstrate that sleep loss exerts significant effects on
      population diversity and function of circulating neutrophils in healthy men. To
      which extent these changes could explain as to why people with poor sleep
      patterns are more susceptible to infections warrants further investigation.

PMID- 24878173
TI  - Visual field progression in glaucoma: what is the specificity of the Guided
      Progression Analysis?
AB  - PURPOSE: To estimate the specificity of the Guided Progression Analysis (GPA)
      (Carl Zeiss Meditec, Dublin, CA) in individual patients with glaucoma. DESIGN:
      Observational cohort study. PARTICIPANTS: Thirty patients with open-angle
      glaucoma. METHODS: In 30 patients with open-angle glaucoma, 1 eye (median mean
      deviation [MD], -2.5 decibels [dB]; interquartile range, -4.4 to -1.3 dB) was
      tested 12 times over 3 months (Humphrey Field Analyzer, Carl Zeiss Meditec; SITA
      Standard, 24-2). "Possible progression" and "likely progression" were determined
      with the GPA. These analyses were repeated after the order of the tests had been
      randomly rearranged (1000 unique permutations). MAIN OUTCOME MEASURES: Rate of
      false-positive alerts of "possible progression" and "likely progression" with the
      GPA. RESULTS: On average, the specificity of the GPA "likely progression" alert
      was high-for the entire sample, the mean rate of false-positive alerts after 10
      follow-up tests was 2.6%. With "possible progression," the specificity was
      considerably lower (false-positive rate, 18.5%). Most important, the cumulative
      rate of false-positive alerts varied substantially among patients, from <1% to
      80% with "possible progression" and from <0.1% to 20% with "likely progression."
      Factors associated with false-positive alerts were visual field variability
      (standard deviation of MD, Spearman's rho = 0.41, P<0.001) and the reliability
      indices (proportion of false-positive and false-negative responses, fixation
      losses, rho>0.31, P<=0.10). CONCLUSIONS: On average, progression criteria
      currently used in the GPA have high specificity, but some patients are more
      likely to show false-positive alerts than others. This is a natural consequence
      of population-based change criteria and may not matter in clinical trials and
      studies in which large groups of patients are compared. However, it must be
      considered when the GPA is used in clinical practice where specificity needs to
      be controlled for individual patients.

PMID- 24878172
TI  - Optimal conduit for diabetic patients: propensity analysis of radial and right
      internal thoracic arteries.
AB  - BACKGROUND: Multiple arterial grafts, in addition to the left internal thoracic
      artery, improve long-term survival after coronary artery bypass grafting (CABG);
      yet, the use of this procedure remains low for both the right internal thoracic
      artery (RITA) and the radial artery (RA). To identify the optimal arterial
      conduit to deploy for revascularization of diabetic patients, we compared the
      outcomes for RA and RITA grafts to the circumflex coronary. METHODS: From January
      1, 1995, to December 31, 2011, 908 consecutive diabetic patients underwent first
      time, isolated CABG (99% on-pump), 659 with the RA and 502 with the RITA,
      respectively, in two affiliated hospitals. Data were prospectively collected, and
      late mortality was determined from the Social Security Death Index. Propensity
      matching, based on preoperative and operative variables, identified 202 matched
      pairs from each group. RESULTS: Long-term survival was similar for matched
      patients. Mortality, myocardial infarction, reoperation for bleeding, stroke,
      sepsis, and renal failure were not significantly different between groups.
      However, deep sternal wound infection (p<0.035) and respiratory failure (p<0.048)
      favored the RA group, in which the total major adverse events were significantly
      fewer (p=0.002). CONCLUSIONS: In diabetic patients undergoing multivessel
      revascularization with either RA or RITA grafts to the circumflex coronary, long
      term survival is similar. However, RA patients experienced significantly fewer
      respiratory or sternal wound adverse events. The RA is the preferred conduit to
      extend to more diabetic patients the recognized survival benefit of a multiple
      arterial graft strategy.

PMID- 24878174
TI  - A control experiment for studies that show improved visual sensitivity with
      intraocular pressure lowering in glaucoma.
AB  - PURPOSE: Contrast sensitivity sometimes increases in patients with open-angle
      glaucoma when intraocular pressure (IOP) is decreased. Although often interpreted
      as demonstrating reversible glaucoma-induced dysfunction, this result, if true,
      could simply reflect a general relationship between sensitivity and IOP in visual
      mechanisms unaffected by glaucoma. To investigate this relationship, we test the
      hypothesis that reducing IOP in eyes without glaucoma (ocular hypertension) does
      not increase perimetric contrast sensitivity. DESIGN: Comparative case series.
      PARTICIPANTS: A total of 692 participants drawn from the Ocular Hypertension
      Treatment Study (OHTS) (22 clinical centers). METHODS: Commercially available
      topical ocular hypotensive medications. MAIN OUTCOME MEASURES: Post hoc analysis
      of IOP and perimetric contrast sensitivity (mean deviation [MD] and pattern
      standard deviation [PSD]) both at baseline (0 months, immediately before ocular
      antihypertensive therapy) and at 6-month review. An additional 618 control eyes
      from OHTS that did not receive treatment were examined over the same period. Data
      from the second phase of OHTS also were examined, and control eyes then received
      treatment. RESULTS: Treated eyes had a decrease in IOP at 6 months (5.1 mmHg,
      P<0.001) but no significant change in MD (0.04 decibels [dB], P = 0.59) or PSD
      (0.03 dB, P = 0.19), relative to controls. A similar decrease in IOP was found
      for eyes that began treatment in the second phase of OHTS, but no significant
      change in MD or PSD. CONCLUSIONS: Despite using a large sample size, we found no
      relationship between perimetric contrast sensitivity and IOP reduction in ocular
      hypertension, which suggests that previous sensitivity changes seen in patients
      with glaucoma, if true, are indicative of reversible glaucoma-induced dysfunction
      rather than a general relationship between sensitivity and IOP in visual
      mechanisms unaffected by glaucoma.

PMID- 24878175
TI  - [The cornea in high axial myopia].
AB  - PURPOSE: To compare corneal characteristics of eyes with high myopia with those
      of eyes with no spherical ametropia using Orbscan and ultrasonic pachymetry.
      METHODS: Orbscan and ultrasonic pachymetry values were prospectively recorded in
      a study group of 105 patients with high myopia (i.e., axial length greater than
      26mm in both eyes) and in a control group of 105 patients with no spherical
      ametropia (absolute value of spherical equivalent less than 1.25D regardless of
      cylinder value). Astigmatism data were expressed by rectangular coordinates in a
      dioptric plane. Axis was decomposed in 2 components (WTR/ATR and oblique) which
      were analyzed by Cos2axis and Sin2axis trigonometric functions. Enantiomorphism
      (mirror-image symmetry) between fellow eyes was quantified by a Euclidean
      distance for the location of the thinnest point and by the difference (in
      absolute value) between 180 degrees  and the sum of both axes for astigmatism.
      RESULTS: In the study group, the mean axial length and subjective spherical
      equivalent were, respectively, 27.82+/-2.14mm (26.00 to 34.06) and -9.00+/-3.46D
      (-4.71 to -19.82). The mean corneal astigmatism was +0.92D*91.3 degrees  in the
      study group and +0.65D*89.3 degrees  in the control group. The mean corneal
      cylinder was higher in the study group (1.44D versus 0.91D; P<0.001) whereas axis
      showed no significant differences between both groups. The mean maximal
      keratometry was steeper in the study group (44.53D versus 44.13D; P=0.03) whereas
      the mean keratometry and minimal keratometry displayed no significant differences
      between both groups. No significant differences in central corneal thickness
      (540.2MUm versus 546.9MUm; P=0.10), peripheral corneal thickness, corneal
      diameter, corneal irregularity, asphericity, and irregular astigmatism were found
      between both groups. There were no significant differences in enantiomorphism
      parameters between both groups. In the study group, correlation with axial length
      was significant only for spherical equivalent (r=-0.86; P<0.001) and corneal
      cylinder (r=0.16; P=0.04). CONCLUSION: High myopia exhibits corneal
      characteristics similar to corneas of eyes with no spherical ametropia, except
      for toricity. While the posterior segment elongates, development of high myopia
      appears not to affect corneal characteristics. Corneal toricity may be associated
      with evolution toward high myopia by perturbing mechanisms of emmetropization.

PMID- 24878176
TI  - [Central corneal thickness in Senegalese melanoderms with primary open angle
      glaucoma].
AB  - PURPOSE: To measure the central corneal thickness (CCT) in Senegalese melanoderms
      with primary open angle glaucoma (POAG) and to determine its effect on visual
      impairment, intraocular pressure, optic nerve and perimetric damage. PATIENTS AND
      METHODS: We studied retrospectively the records of patients followed for POAG
      between May and July 2012. We recorded CCT measured by ultrasonic pachymetry and
      results of the first clinical examinations, including best-corrected visual
      acuity (CVA), intraocular pressure (IOP) by Goldmann tonometry, cup-to-disc ratio
      (C/D), and visual fields by automated perimetry according to the classification
      of Hodapp. RESULTS: Two hundred and thirty-four eyes of 117 patients were
      enrolled. Mean age was 56.53 +/- 11.29 years and gender ratio was 2.77. Mean CCT
      was 525.40 +/- 39.63 MUm for all eyes, right and left (P=0.734). Women had a mean
      CCT of 521.20 +/- 36.20 MUm and men 526.91 +/- 40.79 MUm (P=0.332). Corneas were
      thinner in patients over 50 years (P=0.0047), in eyes having a CVA<3/10 (P=0.01)
      or a C/D >= 0.8 (P=0.043). CCT had no correlation with frequency of ocular
      hypertension (P=0.16) or advanced visual field defect (P=0.33). CONCLUSION: CCT
      of glaucomatous Senegalese is independent of laterality and sex, but decreased
      with age. A thin cornea is a risk for visual loss and optic cup enlargement, thus
      the importance of systematic measurement of CCT.

PMID- 24878178
TI  - Facile synthesis of multilayered polysaccharidic vesicles.
AB  - In this study, we developed facile synthesis method of multilayered
      polysaccharidic vesicles (hereafter termed 'mPSVs') using polysaccharides such as
      starch, hyaluronate (HA), and glycol chitosan (GC) via simple chemistry and using
      enzymatic reactions among polysaccharides. The enzymatic degradation of the HA
      shell by hyaluronidase (HYAL) enzyme contributed to accelerate the release of
      protein/peptide from the mPSVs. The mPSVs containing folate ligand and apoptotic
      cell death-inducing D-(KLAKLAK)2 peptide were effectively accumulated in in vivo
      KB tumor cells, primarily owing to passive tumor penetration via the enhanced
      permeability and retention (EPR) effect and active targeting via specific binding
      to folate receptors expressed on KB tumor cells. These mPSVs resulted in a
      significant increase in the in vivo tumor inhibition. This vesicle system is
      expected to exhibit great potential as an advanced platform technology for
      biomedical applications involving small molecular drugs with protein/gene
      targets. 

PMID- 24878177
TI  - hZIP1 that is down-regulated in clear cell renal cell carcinoma is negatively
      associated with the malignant potential of the tumor.
AB  - OBJECTIVE: The human ZRT, IRT-like protein 1 (hZIP1) has been associated with
      tumorigenesis. However, its role in clear cell renal cell carcinoma (ccRCC) has
      not been yet reported. The objective was to investigate hZIP1 expression in ccRCC
      and its association with clinicopathological features. MATERIALS AND METHODS: A
      total of 106 ccRCC tissue samples and corresponding normal kidney tissue samples
      were examined, along with 3 ccRCC cell lines (ACHN, 769-P, and 786-O). Real-time
      polymerase chain reaction, Western blot, and immunohistochemistry were used to
      investigate the expression of hZIP1 and its relationship with clinicopathological
      features. The ACHN cell line, exhibiting the highest hZIP1 expression, was
      transfected with hZIP1 small interfering RNA or mock small interfering RNA.
      Cellular proliferation was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide assay. Invasion was determined by Transwell assay.
      RESULTS: The level of hZIP1 was decreased in ccRCC tissues when compared with
      normal tissues. hZIP1 expression significantly decreased with increasing clinical
      stage and pathological grade in ccRCC samples (P<0.05), showing a significant
      negative correlation with the histological grade (P<0.05). High hZIP1 expression
      was associated with a better disease-free survival (P<0.01). Silencing of hZIP1
      expression enhanced the proliferative and invasive abilities of ACHN cells.
      CONCLUSIONS: Results suggest that hZIP1 may act as a tumor suppressor in ccRCC.
      hZIP1 is closely correlated with clinicopathological features. High hZIP1
      expression may be an indicator of good prognosis in ccRCC.

PMID- 24878179
TI  - Biodegradable nanoparticles for intracellular delivery of antimicrobial agents.
AB  - Biodegradable nanoparticles have emerged as a promising strategy for ferrying
      antimicrobial agents into specific cells due to their unique properties. This
      review discusses the current progress and challenges of biodegradable
      nanoparticles for intracellular antimicrobial delivery to understand design
      principles for the development of ideal nanocarriers. The intracellular delivery
      performances of biodegradable nanoparticles for diverse antimicrobial agents are
      first summarized. Second, the cellular internalization and intracellular
      trafficking, degradation and release kinetics of nanoparticles as well as their
      relation with intracellular delivery of encapsulated antimicrobial agents are
      provided. Third, the influences of nanoparticle properties on the cellular
      internalization and intracellular fate of nanoparticles and their payload
      antimicrobial agents are discussed. Finally, the challenges and perspectives of
      nanoparticles for intracellular delivery of antimicrobial agents are addressed.
      The review will be helpful to the scientists who are interested in searching for
      more efficient nanosystem strategies for intracellular delivery of antimicrobial
      agents. 

PMID- 24878180
TI  - Respirable nanocarriers as a promising strategy for antitubercular drug delivery.
AB  - Tuberculosis is considered a fatal respiratory infectious disease that represents
      a global threat, which must be faced. Despite the availability of oral
      conventional anti-tuberculosis therapy, the disease is characterized by high
      progression. The leading causes are poor patient compliance and failure to adhere
      to the drug regimen primarily due to systemic toxicity. In this context,
      inhalation therapy as a non-invasive route of administration is capable of
      increasing local drug concentrations in lung tissues, the primary infection side,
      by passive targeting as well as reducing the risk of systemic toxicity and hence
      improving the patient compliance. Nanotechnology represents a promising strategy
      in the development of inhaled drug delivery systems. Nanocarriers can improve the
      drug effectiveness and decrease the expected side effects as consequences of
      their ability to target the drug to the infected area as well as sustain its
      release in a prolonged manner. The current review summarizes the state-of-the-art
      in the development of inhaled nanotechnological carriers confined currently
      available anti-tuberculosis drugs (anti TB) for local and targeting drug delivery
      specifically, polymeric nanoparticles, solid lipid nanoparticles, nanoliposomes
      and nanomicelles. Moreover, complexes and ion pairs are also reported. The impact
      and progress of nanotechnology on the therapeutic effectiveness and patient
      adherence to anti TB regimen are addressed. 

PMID- 24878181
TI  - Cell and biomolecule delivery for tissue repair and regeneration in the central
      nervous system.
AB  - Tissue engineering frequently involves cells and scaffolds to replace damaged or
      diseased tissue. It originated, in part, as a means of effecting the delivery of
      biomolecules such as insulin or neurotrophic factors, given that cells are
      constitutive producers of such therapeutic agents. Thus cell delivery is
      intrinsic to tissue engineering. Controlled release of biomolecules is also an
      important tool for enabling cell delivery since the biomolecules can enable cell
      engraftment, modulate inflammatory response or otherwise benefit the behavior of
      the delivered cells. We describe advances in cell and biomolecule delivery for
      tissue regeneration, with emphasis on the central nervous system (CNS). In the
      first section, the focus is on encapsulated cell therapy. In the second section,
      the focus is on biomolecule delivery in polymeric nano/microspheres and hydrogels
      for the nerve regeneration and endogenous cell stimulation. In the third section,
      the focus is on combination strategies of neural stem/progenitor cell or
      mesenchymal stem cell and biomolecule delivery for tissue regeneration and
      repair. In each section, the challenges and potential solutions associated with
      delivery to the CNS are highlighted. 

PMID- 24878182
TI  - Conventional versus stealth lipid nanoparticles: formulation and in vivo fate
      prediction through FRET monitoring.
AB  - The determination of the nanocarrier fate in preclinical models is required
      before any translation from laboratory to clinical trials. Modern fluorescent
      imaging techniques have gained considerable advances becoming a powerful
      technology for non-invasive visualization in living subjects. Among them, Forster
      (fluorescence) resonance energy transfer (FRET) is a particular fluorescence
      imaging which involves energy transfer between 2 fluorophores in a distance
      dependent manner. Considering this feature, the encapsulation of an
      acceptor/donor pair in lipid nanoparticles (LNEs: lipid nanoemulsions, LNCs:
      lipid nanocapsules) allowed the carrier integrity to be tracked. Accordingly, we
      used this FRET technique to evaluate the behavior of LNEs, conventional LNCs and
      newly designed stealth LNCs. After the development through a one-step (OS)
      PEGylation process of these stealth LNCs (OS LNCs), in vitro guest exchange
      dynamics and release kinetics were evaluated for both LNC formulations. We
      thereafter assessed in vivo biodistribution of all types of lipid nanoparticles.
      Results showed enhanced stability of encapsulation in OS LNCs in comparison to
      conventional LNCs. Additionally, the presence of the long PEG chains on the lipid
      nanoparticle surface altered the biodistribution pattern. Despite different
      release kinetic profiles, OS LNCs and LNEs showed extended blood circulation time
      associated with a good structure stability over several hours after intravenous
      injection. 

PMID- 24878183
TI  - Liposomal corticosteroids for the treatment of inflammatory disorders and cancer.
AB  - Glucocorticoids (GC) are known for their potent immunosuppressive and anti
      inflammatory properties. As a consequence, they have been extensively used for
      the treatment of many different diseases. Prolonged and/or high-dose GC therapy,
      however, generally comes with severe side effects, resulting not only from their
      very diverse mechanism(s) of action, but also from their relatively poor
      biodistribution. Drug delivery systems, and in particular liposomes, have been
      extensively used to enhance the biodistribution and the target site accumulation
      of GC, and to thereby improve the balance between their efficacy and their
      toxicity. Many different types of liposomes have been employed, and both local
      and systemic treatments have been evaluated. We here summarize the progress made
      in the use of liposomal GC formulations for the treatment of asthma, rheumatoid
      arthritis, multiple sclerosis and cancer, and we show that the targeted delivery
      of GC to pathological sites holds significant clinical potential. 

PMID- 24878185
TI  - Thermally triggered release of a pro-osteogenic peptide from a functionalized
      collagen-based scaffold using thermosensitive liposomes.
AB  - Collagen is one of the most attractive materials for the development of matrices
      for tissue engineering, due to its excellent biocompatibility and non-toxic
      bioresorption. The present work describes a collagen-based externally controlled
      drug-eluting scaffold which consists of drug encapsulated thermoresponsive
      liposomes covalently attached to the surface of a functionalized collagen-based
      scaffold. The model drug used in this work was PTHrP 107-111, a pentapeptide with
      pro-osteogenic and antiosteoclastic activity. An osteoconductive collagen
      hydroxyapatite scaffold, designed specifically for bone repair, was used as a
      model scaffold. The results demonstrate that it is possible to modify the
      kinetics of release of the drug from the scaffold with the application of an
      external thermal stimulus (42 degrees C, 20min). In vitro studies carried out
      with pre-osteoblastic MC3T3-E1 cells demonstrated that neither the attachment of
      liposomes to the surface of the scaffolds nor the hyperthermic pulse negatively
      affected the ability of cells to attach and proliferate on the scaffolds.
      Importantly, the on-demand release of PTHrP 107-111 had a pro-osteogenic effect,
      as shown by the enhancement of alkaline phosphatase activity, an early osteogenic
      marker, which correlated with increased expression of the osteogenic genes
      osteopontin and osteocalcin. In conclusion, the scaffold-based release system
      developed in this study has immense potential for tuning the delivery of a
      diverse range of drugs which can be applied for the regeneration of a variety of
      tissue types. 

PMID- 24878186
TI  - Prolonged survival upon ultrasound-enhanced doxorubicin delivery in two syngenic
      glioblastoma mouse models.
AB  - Glioblastoma multiforme (GBM) is the most common and most aggressive malignant
      primary brain tumor in humans with a very poor prognosis. Chemotherapeutical
      treatment of GBMs is limited by the blood-brain barrier (BBB). This physical and
      metabolic barrier separates the blood from the brain parenchyma and prevents the
      entry of toxins but also of potentially useful chemotherapeutics from the blood
      into the brain. Microbubble-enhanced focused ultrasound (MB-FUS) has been
      proposed to disrupt locally and reversibly the BBB to facilitate diffusion of
      drugs from the micro vasculature into brain tissue. The present study
      investigates the feasibility and the safety of such an approach in two syngenic
      mouse models of GBM (GL261 and SMA-560). Local doxorubicin (DOX) concentration in
      MB-FUS sonicated normal brain tissue as well as in brain tumor tissue was
      increased as compared to the unsonicated control tissue in the contralateral
      hemisphere. Moreover, ultrasound mediated BBB disruption, in combination with DOX
      therapy, resulted in a significant increase of survival and in a slower disease
      progression in the two syngenic GBM mouse models. In conclusion, our results
      confirm that MB-ultrasound might ultimately be an effective technology to improve
      the therapy of GBM, and they provide for the first time evidence that combining
      MB-FUS with DOX treatment is effective in syngenic mouse models for GBM which can
      serve as preclinical models to study the impact of immune system on the
      therapeutic application of MB-FUS chemotherapy. 

PMID- 24878187
TI  - Toward the redesign of nutrition delivery.
AB  - In the facilitation of widespread access to low-cost, good tasting food, the
      global food system has relied on the use of fat, sugar, chemical processing aids
      and plastics, among other elements potentially detrimental to human health and
      the environment. This contrasts starkly with the strategies of natural nutrition
      delivery systems. Rich in vitamins, minerals, and other substances of functional
      benefit to human health, natural delivery systems, such as fruits and vegetables,
      retain their physical and chemical stability in a range of conditions over
      relatively long times through protective skins and shells that can either be
      eaten or degrade rapidly and fully in nature. Frequently natural foods can be
      delivered in small (even extremely small) portions, as with berries, insects,
      plankton and krill, permitting portion control and the rapid and efficient
      delivery of functional nutrition in inherently mobile circumstances. These and
      other qualities, which have insured the sustainable and healthy nourishment of
      animals and humans for at least tens of thousands of years, are often absent from
      today's man-made food and beverage delivery systems. With growing awareness of
      the liabilities to maintaining the food system of today, efforts are now underway
      to redesign nutrition delivery so as to provide the contemporary benefits of
      global access while retrieving the health and environmental benefits associated
      with natural delivery systems. We review these here, with special attention to
      recently commercialized nutritional delivery systems emerging from the drug
      delivery field aimed at reducing waste in food and beverage (nutritional
      aerosols) and eliminating waste in food and beverage packaging (edible skins). We
      briefly discuss the potential ramifications to how we will eat tomorrow. 

PMID- 24878189
TI  - [Afatinib (BIBW 2992)].
AB  - Afatinib (BIBW 2992) is an irreversible multi-target HER receptor tyrosine kinase
      inhibitor developed in patients with advanced solid tumours. Several phase I
      studies were conducted in patients with non-small cell lung cancer (NSCLC), as a
      single agent or in combination. In further phase II or III studies, patients were
      selected based on the duration of response to first generation EGFR-TKI in
      previous line (supposed to have greater chance to have an activating EGFR
      mutation) or based directly on the EGFR activating mutation status. Here, we
      report and comment the main results of these studies in lung cancer patients.
      This drug has been approved by the Food and Drug Administration in June 2013 for
      the first-line treatment of patients with metastatic NSCLC whose tumours have
      EGFR mutation. In Europe, it has been approved in September 2013 in the same
      indication. 

PMID- 24878188
TI  - [Fight against tuberculosis in the world].
AB  - Tuberculosis (TB) in a major health problem in the world. WHO and its partners
      especially, the stop TB partnership launched numerous strategies against TB
      especially in the 1990. Strategy DOTS (directly observed therapy short course)
      was launched in 1995. One main key was the direct supervision of drug intake by
      patients. Progress was achieved but it was insufficient. A new strategy called
      "Stop TB Strategy 2006-2015" was launched in 2006 in the context of Millennium
      Development Goals (MDG) elaborated by United Nations. The common goals were to
      halt and start to reverse the incidence of TB, reduce the prevalence and death
      rate by 50% compared to their level in 1990 by 2015 to eliminate TB as a public
      health problem by 2050. The end of 2010 marks the mid-point of the Global Plan
      and is an obvious time to update it and take into account actual progress with a
      focus on the 2015 to reach goals. So an updated Global Plan to stop TB 2011-2015,
      was launched. Expected progress and targets were defined for 2015, in diagnosis
      and treatment, in co-infection TB/HIV, in drug-resistant TB and achievements
      expected in new tests for diagnosis, new medications, new vaccines and new
      regimens with shorter duration of treatment. WHO and partners have started
      discussions to define the new post 2015 strategy to TB control and elimination.
      Risk factors (diabetes, malnutrition, tobacco smoke...) and socioeconomic
      factors, which are associated with TB, should be included in the new strategy to
      eliminate TB in 2050. 

PMID- 24878190
TI  - [A rare cause of anosmia: nasosinusal tuberculosis].
AB  - We report the case of a 46-year-old-woman who presented with anosmia and nasal
      obstruction. Primary nasal tuberculosis was discovered. Primary nasal
      tuberculosis is very rare. Women are more touched than men. Symptomatology is
      often unilateral with nasal obstruction, anterior rhinorrhea or epistaxis.
      Diagnosis relies on the anatomopathologic and bacteriological examinations. The
      treatment is mainly medical based on antituberculosis drugs. In the light of this
      case report, a review of the literature was made.

PMID- 24878191
TI  - Role of progesterone in melatonin-mediated protection against acute kidney
      injury.
AB  - BACKGROUND: Melatonin is released by pineal gland and maintains circadian rhythm
      in the body. It has been reported as renoprotective agent because of its
      antioxidant property. Recently, a cross talk between progesterone and melatonin
      has been observed in various preclinical studies. The present study investigated
      the involvement of progesterone receptors in melatonin-mediated protection
      against ischemia reperfusion induced acute kidney injury (AKI) in rats. MATERIALS
      AND METHODS: The rats were subjected to bilateral renal ischemia for 40 min
      followed by reperfusion for 24 h to induce AKI. The AKI was assessed by measuring
      creatinine clearance, serum urea, uric acid level, potassium level, fractional
      excretion of sodium, lactate dehydrogenase activity, and microproteinuria. The
      oxidative stress in renal tissues was assessed by quantification of
      myeloperoxidase activity, thiobarbituric acid reactive substances, superoxide
      anion generation, reduced glutathione level, and catalase activity. The
      hematoxylin-eosin staining was carried out to observe histopathologic changes in
      renal tissues. The melatonin (4 and 10 mg/kg, intraperitoneally) and progesterone
      receptor antagonist mifepristone (5 mg/kg, intraperitoneally) were used in the
      present study. RESULTS: The renal ischemia reperfusion induced AKI as indicated
      by significant change in serum, urinary, and tissue parameters that was
      ameliorated by prior treatment with melatonin. No significant difference in serum
      progesterone level was observed between various groups used in the present study.
      The prior administration of mifepristone abolished melatonin-mediated protection
      against AKI. CONCLUSIONS: It is concluded that melatonin treatment affords
      protection against ischemia reperfusion induced AKI. Moreover, progesterone
      receptors are essentially involved in mediating protective role of melatonin
      against AKI in rats.

PMID- 24878192
TI  - Design, synthesis, in vitro evaluation and preliminary SAR studies of N-(2
      (heteroaryloxy)propyl)phenothiazines against Rhipicephalus microplus cattle tick.
AB  - A family of 15 N-substituted phenothiazines was designed, synthesized and their
      acaricidal activity against Rhipicephalus microplus was determined in vitro. The
      synthetic methodology is simple and can be employed in multigram scale. The
      rationale for the structure-based design of these compounds is the potential for
      azines and phenothiazine to engage in pi-pi interactions; these fragments, joined
      together by a short, flexible alkoxide linker, structurally resemble
      phenothiazine-based cholinesterase inhibitors, while their weak basicity implies
      a neutral active form, rather than a cationic one, thus facilitating penetration
      of the cuticle of ticks. One compound displayed excellent acaricidal activity
      (LD50=0.58 MUg/mL). Preliminary SAR analysis suggests that the activity is
      influenced by the presence of a weakly basic nitrogen atom, as well as the
      substitution pattern within the heterocycles.

PMID- 24878184
TI  - Prostate cancer relevant antigens and enzymes for targeted drug delivery.
AB  - Chemotherapy is one of the most widely used approaches in combating advanced
      prostate cancer, but its therapeutic efficacy is usually insufficient due to poor
      specificity and associated toxicity. Lack of targeted delivery to prostate cancer
      cells is also the primary obstacles in achieving feasible therapeutic effect of
      other promising agents including peptide, protein, and nucleic acid.
      Consequently, there remains a critical need for strategies to increase the
      selectivity of anti-prostate cancer agents. This review will focus on various
      prostate cancer-relevant antigens and enzymes that could be exploited for
      prostate cancer targeted drug delivery. Among various targeting strategies,
      active targeting is the most advanced approach to specifically deliver drugs to
      their designated cancer cells. In this approach, drug carriers are modified with
      targeting ligands that can specifically bind to prostate cancer-specific
      antigens. Moreover, there are several specific enzymes in the tumor
      microenvironment of prostate cancer that can be exploited for stimulus-responsive
      drug delivery systems. These systems can specifically release the active drug in
      the tumor microenvironment of prostate cancer, leading to enhanced tumor
      penetration efficiency. 

PMID- 24878193
TI  - Design, synthesis and biological evaluation of benzyl 2-(1H-imidazole-1-yl)
      pyrimidine analogues as selective and potent Raf inhibitors.
AB  - The synthesis of a novel series of (4-aminobenzyl/benzoyl)-1H-imidazol-1-yl
      pyrimidin-2-yl derivatives 9, 10, 18, 19 and their in vitro antiproliferative
      activities against the A375P human melanoma cell line and the U937 human leukemic
      monocyte lymphoma cell line are described. Potent antiproliferative effects were
      found from 9l, 9s and 10c; 10c was found to be a highly potent and selective BRAF
      V600E and CRAF inhibitor (IC50=38.3 nM and 8.79 nM).

PMID- 24878194
TI  - Synthetically modified L-histidine-rich peptidomimetics exhibit potent activity
      against Cryptococcus neoformans.
AB  - We describe the synthesis and antimicrobial evaluation of structurally new
      peptidomimetics, rich in synthetically modified L-histidine. Two series of
      tripeptidomimetics were synthesized by varying lipophilicity at the C-2 position
      of L-histidine and at the N- and C-terminus. The data indicates that peptides
      (5f, 6f, 9f and 10f) possessing highly lipophilic adamantan-1-yl group displayed
      strong inhibition of Cryptococcus neoformans. Peptide 6f is the most potent of
      all with IC50 and MFC values of 0.60 and 0.63 MUg/mL, respectively, compared to
      the commercial drug amphotericin B (IC50=0.69 and MFC=1.25 MUg/mL). The
      selectivity of these peptides to microbial pathogen was examined by a tryptophan
      fluorescence quenching study and transmission electron microscopy. These studies
      indicate that the peptides plausibly interact with the mimic membrane of pathogen
      by direct insertion, and results in disruption of membrane of pathogen.

PMID- 24878195
TI  - Synthesis of novel 4-nitropyrrole-based semicarbazide and thiosemicarbazide
      hybrids with antimicrobial and anti-tubercular activity.
AB  - We report the synthesis and screening of forty novel 4-nitropyrrole-semicarbazide
      conjugates inspired from the reported bio-potential of bromopyrrole alkaloids and
      semicarbazide derivatives for antimicrobial activity. Herein, hybrids 5k-5o, 5r,
      5s and 5t displayed four-fold increased activity (MIC=0.39 MUg/mL) against
      Escherichia coli compared to standard ciprofloxacin. Eight hybrids, 5k-5o and 5r
      5t displayed equal antibacterial activity (MIC=1.56 MUg/mL) against Klebsiella
      pneumonia compared to standard ciprofloxacin. Hybrid, 5k-5o (MIC=0.195 MUg/mL)
      displayed highly potent antibacterial activity against MSSA as compared to
      standard ciprofloxacin. Eight-fold superior activity was observed for four
      hybrids 5k-5m and 5o (MIC=0.39 MUg/mL) against MRSA. Further, nine hybrids
      displayed four-fold superior antifungal activity (MIC=0.78 MUg/mL) compared to
      standard Amphotericin B. Encouraging MICs of these hybrids recognize them as
      promising leads for development of potential antimicrobial drugs.

PMID- 24878196
TI  - Theophylline-7-acetic acid derivatives with amino acids as anti-tuberculosis
      agents.
AB  - A series of amides were synthesized by condensation of theophylline-7-acetic acid
      and eight commercially available amino acid methyl ester hydrochlorides.
      Consecutive hydrolysis of six of the amido-esters resulted in the formation of
      corresponding amido-acids. The newly synthesized compounds were evaluated for
      their in vitro activity against Mycobacterium tuberculosis H37Rv. The activity
      varied depending on the amino acid fragments and in seven cases exerted excellent
      values with MICs 0.46-0.26 MUM. Assessment of the cytotoxicity revealed that the
      compounds were not cytotoxic against the human embryonal kidney cell line HEK
      293T. The theophylline-7-acetamides containing amino acid moieties appear to be
      promising lead compounds for the development of antimycobacterial agents.

PMID- 24878198
TI  - Naturally occurring polyphenolic inhibitors of amyloid beta aggregation.
AB  - Alzheimer's disease is the most common neurodegenerative disease and is one of
      the main causes of death in developed countries. Consumption of foods rich in
      polyphenolics is strongly correlated with reduced incidence of Alzheimer's
      disease. Our study has investigated the biological activity of previously
      untested polyphenolic compounds in preventing amyloid beta aggregation. The anti
      aggregatory potential of these compounds was assessed using the Thioflavin-T
      assay, transmission electron microscopy, dynamic light scattering and size
      exclusion chromatography. Two structurally related compounds, luteolin and
      transilitin were identified as potent inhibitors of Abeta fibril formation.
      Computational docking studies with an X-ray derived oligomeric structure offer a
      rationale for the inhibitory activity observed and may facilitate development of
      improved inhibitors of Abeta aggregation and toxicity. 

PMID- 24878197
TI  - Synthesis and evaluation of (18)F-labeled tertiary benzenesulfonamides for
      imaging carbonic anhydrase IX expression in tumours with positron emission
      tomography.
AB  - Three tertiary benzenesulfonamide inhibitors 4a-c were radiolabeled with (18)F
      and evaluated for imaging carbonic anhydrase IX (CA IX) expression with positron
      emission tomography. All three inhibitors exhibit <10 nM affinity for CA IX with
      no measurable affinity for CA II. Despite good affinity/selectivity to CA IX and
      excellent stability in plasma, uptake of [(18)F]4a-c in CA IX-expressing HT-29
      tumours was low without significant contrast. [(18)F]4a,b were excreted rapidly,
      while [(18)F]4c exhibited significant in vivo defluorination leading to high bone
      uptake. Due to minimal uptake in HT-29 tumours compared to normal organs/tissues,
      (18)F-labeled benzenesulfonamides [(18)F]4a-c are not suitable as CA IX imaging
      agents.

PMID- 24878199
TI  - Dysoxylum binectariferum bark as a new source of anticancer drug camptothecin:
      bioactivity-guided isolation and LCMS-based quantification.
AB  - Camptothecin (CPT, 1) is a potent anticancer natural product which led to the
      discovery of two clinically used anticancer drugs topotecan and irinotecan. These
      two drugs are semisynthetic analogs of CPT, and thus the commercial production of
      CPT as a raw material from various plant sources and tissue culture methods is
      highly demanding. In the present study, the Dysoxylum binectariferum bark, was
      identified as an alternative source of CPT, through bioassay-guided isolation.
      The barks showed presence of CPT (1) and its 9-methoxy analog 2, whereas CPT
      alkaloids were not present in seeds and leaves. This is the first report on
      isolation of CPT alkaloids from Meliaceae family. An efficient chromatography
      free protocol for enrichment and isolation of CPT from D. binectariferum has been
      established, which was able to enrich CPT up to 21% in the crude extract. The
      LCMS (MRM)-based quantification method revealed the presence of 0.105% of CPT in
      dry barks of D. binectariferum. The discovery of CPT from D. binectariferum bark
      will certainly create a global interest in cultivation of this plant as a new
      crop for commercial production of CPT. Isolation of anticancer drug CPT from this
      plant, indicates that along with rohitukine, CPT and 9-methoxy CPT also
      contributes significantly to the cytotoxicity of D. binectariferum. 

PMID- 24878200
TI  - [FeFe]-hydrogenase maturation.
AB  - Hydrogenases are metalloenzymes that catalyze the reversible reduction of protons
      at unusual metal centers. This Current Topic discusses recent advances in
      elucidating the steps involved in the biosynthesis of the complex metal cluster
      at the [FeFe]-hydrogenase (HydA) active site, known as the H-cluster. The H
      cluster is composed of a 2Fe subcluster that is anchored within the active site
      by a bridging cysteine thiolate to a [4Fe-4S] cubane. The 2Fe subcluster contains
      carbon monoxide, cyanide, and bridging dithiolate ligands. H-cluster biosynthesis
      is now understood to occur stepwise; standard iron-sulfur cluster assembly
      machinery builds the [4Fe-4S] cubane of the H-cluster, while three specific
      maturase enzymes known as HydE, HydF, and HydG assemble the 2Fe subcluster. HydE
      and HydG are both radical S-adenosylmethionine enzymes that interact with an iron
      sulfur cluster binding GTPase scaffold, HydF, during the construction of the 2Fe
      subcluster moiety. In an unprecedented biochemical reaction, HydG cleaves
      tyrosine and decomposes the resulting dehydroglycine into carbon monoxide and
      cyanide ligands. The role of HydE in the biosynthetic pathway remains undefined,
      although it is hypothesized to be critical for the synthesis of the bridging
      dithiolate. HydF is the site where the complete 2Fe subcluster is formed and
      ultimately delivered to the immature hydrogenase protein in the final step of
      [FeFe]-hydrogenase maturation. This work addresses the roles of and interactions
      among HydE, HydF, HydG, and HydA in the formation of the mature [FeFe]
      hydrogenase. 

PMID- 24878201
TI  - Combined sequence and sequence-structure-based methods for analyzing RAAS gene
      SNPs: a computational approach.
AB  - The renin-angiotensin-aldosterone system (RAAS) plays a key role in the
      regulation of blood pressure (BP). Mutations on the genes that encode components
      of the RAAS have played a significant role in genetic susceptibility to
      hypertension and have been intensively scrutinized. The identification of such
      probably causal mutations not only provides insight into the RAAS but may also
      serve as antihypertensive therapeutic targets and diagnostic markers. The methods
      for analyzing the SNPs from the huge dataset of SNPs, containing both functional
      and neutral SNPs is challenging by the experimental approach on every SNPs to
      determine their biological significance. To explore the functional significance
      of genetic mutation (SNPs), we adopted combined sequence and sequence-structure
      based SNP analysis algorithm. Out of 3864 SNPs reported in dbSNP, we found 108
      missense SNPs in the coding region and remaining in the non-coding region. In
      this study, we are reporting only those SNPs in coding region to be deleterious
      when three or more tools are predicted to be deleterious and which have high RMSD
      from the native structure. Based on these analyses, we have identified two SNPs
      of REN gene, eight SNPs of AGT gene, three SNPs of ACE gene, two SNPs of AT1R
      gene, three SNPs of CYP11B2 gene and three SNPs of CMA1 gene in the coding region
      were found to be deleterious. Further this type of study will be helpful in
      reducing the cost and time for identification of potential SNP and also helpful
      in selecting potential SNP for experimental study out of SNP pool.

PMID- 24878203
TI  - Applying for fellowships in the United States: an expensive and risky
      proposition.

PMID- 24878204
TI  - [Prenatal diagnosis of gallbladder abnormalities: a review].
AB  - OBJECTIVES: Our objective was to review the possible consequences and management
      possibilities of fetal gallbladder abnormalities. MEANS AND METHODS: A search
      through publications was conducted using the Pubmed database. RESULT: The
      majority of fetal gallbladder abnormalities are benign (absence, malformation,
      cholelithiasis, sludge...). When the absence of gallbladder is isolated, biliary
      tract atresia, that is a rare but severe disease, must be evoked. CONCLUSION: An
      extensive morphological analysis of the fetus is required in cases with
      gallbladder abnormalities. An amniocentesis for caryotype analysis must be
      proposed when an absent gallbladder is associated with other fetal abnormalities
      and in all cases of absent gallbladder for digestive enzymes evaluation to rule
      out a biliary atresia.

PMID- 24878205
TI  - Nutritional support for premature infants in the neonatal intensive care unit.
AB  - Nutritional support for premature infants in the neonatal intensive care unit
      setting is complex. Such infants have conditions unique to this period of the
      lifespan requiring specialized care management, both of which may impede the
      provision of adequate nutrition to support basal metabolic needs. Premature
      infants require optimum nutritional intake to support rapid growth during a time
      when they are not fully capable of tolerating it. This article reviews
      developmental anatomy, physiology, and the effect of premature delivery by
      systems; the challenges of providing adequate nutrition; and current evidence
      based strategies to provide nutrition for premature infants during
      hospitalization. 

PMID- 24878206
TI  - Nutrition in the pediatric population in the intensive care unit.
AB  - Nutrition is an essential component of patient management in the pediatric
      intensive care unit (PICU). Poor nutrition status accompanies many childhood
      chronic illnesses. A thorough assessment of the critically ill child is required
      to inform the plan for nutrition support. Accurate and clinically relevant
      nutritional assessment, including growth measurements, provides important
      guidance. Indirect calorimetry provides the most accurate measurement of resting
      energy expenditure, but is too often unavailable in the PICU. To prevent
      inappropriate caloric intake, reassessment of the child's nutrition status is
      imperative. Enteral nutrition is the recommended route of intake. Human milk is
      preferred for infants. 

PMID- 24878207
TI  - Nutrition in the chronically ill critical care patient.
AB  - Chronic critical illness is a problem in the critical care environment. The
      ultimate goal in managing care for the chronically critically ill is liberation
      from mechanical ventilation, leading to improved survival and enhanced quality of
      life. Clinical practice guidelines are presented as a framework in providing care
      for this distinct patient population. Research studies supplement the
      recommendations to ensure best care guides critical care decisions using the best
      evidence in the context of patient values and clinical expertise. 

PMID- 24878208
TI  - Malnutrition in the ICU patient population.
AB  - Malnutrition has been identified as a cause for disease as well as a condition
      resulting from inflammation associated with acute or chronic disease.
      Malnutrition is common in acute-care settings, occurring in 30% to 50% of
      hospitalized patients. Inflammation has been associated with malnutrition and
      malnutrition has been associated with compromised immune status, infection, and
      increased intensive care unit (ICU) and hospital length of stay. The ICU nurse is
      in the best position to advocate for appropriate nutritional therapies and
      facilitate the safe delivery of nutrition. 

PMID- 24878209
TI  - Nutrition and care considerations in the overweight and obese population within
      the critical care setting.
AB  - Nutrition and care considerations in the overweight and obese population within
      the critical care setting are multifaceted. Patients requiring critical care have
      specialized care management needs that often times challenge health care
      providers. When patients are obese, this further complicates the physiologic
      aspects of healing, thus creating challenges to meeting both the nutritional
      needs of the individual and hampering treatment. This article reviews the care
      considerations, physiology of bariatric patients, and challenges of providing
      safe and quality care, including current evidence-based practice strategies
      developed to provide optimal support for obese patients during hospitalization
      and within the critical care setting. 

PMID- 24878210
TI  - Nutritional requirements after bariatric surgery.
AB  - This article presents an overview of postoperative nutritional requirements and
      goals following bariatric surgery. It summarizes current diet progression and
      nutrient intake guidelines geared toward optimizing weight loss and maintaining
      adequate nutritional status, nutrient absorption, as well as hydration. The
      article further emphasizes the importance of postoperative follow-up with a
      bariatric multidisciplinary team for appropriate postoperative care, diet
      management, and nutrient deficiency screenings. 

PMID- 24878211
TI  - Bedside caregivers as change agents: implementation of early enteral nutrition in
      critical care.
AB  - Enteral nutrition is an important aspect of caring for critically ill patients,
      yet delays in implementation of guidelines and recommendations occur. Bedside
      caregivers are in a key position to evaluate current practice and lead change to
      implement evidence-based practice guidelines. Interdisciplinary teams can use
      change models, such as Larrabee's, to provide guidance and support success of
      practice change projects. 

PMID- 24878212
TI  - Nutrition as medical therapy.
AB  - Recent data support the use of nutritional agents for use as targeted medical
      therapy. This article reviews some of the pharmacologic roles that parenteral
      nutritional ingredients (selenium, lipid emulsion, insulin, and levocarnitine)
      can play in the setting of critical illness. 

PMID- 24878213
TI  - Nutrition in critical illness.

PMID- 24878214
TI  - Coming to grips with challenging behavior: a cluster randomized controlled trial
      on the effects of a multidisciplinary care program for challenging behavior in
      dementia.
AB  - OBJECTIVES: The Grip on Challenging Behavior care program was developed using the
      current guidelines and models on managing challenging behavior in dementia in
      nursing homes. It was hypothesized that the use of the care program would lead to
      a decrease in challenging behavior and in the prescription of psychoactive drugs
      without increase in use of restraints. DESIGN: A randomized controlled trial was
      undertaken using a stepped-wedge design to implement the care program and to
      evaluate the effects. An assessment of challenging behavior and psychoactive
      medication was undertaken every 4 months on all participating units followed by
      the introduction of the care program in a group of 3 to 4 units. A total of 6
      time assessments took place over 20 months. SETTING: Seventeen dementia special
      care units of different nursing homes. PARTICIPANTS: A total of 659 residents of
      dementia special care units. All residents with dementia on the unit were
      included. Units were assigned by random allocation software to 1 of 5 groups with
      different starting points for the implementation of the care program.
      INTERVENTION: A care program consisting of various assessment procedures and
      tools, which ensure a multidisciplinary approach and which structure the process
      of managing challenging behavior in dementia. MEASUREMENTS: Challenging behavior
      was measured using the Cohen-Mansfield Agitation Inventory (CMAI) and the
      Neuropsychiatric Inventory. Research assistants (blinded for intervention status
      of the unit) interviewed nurses on the units about challenging behavior. Data on
      psychoactive drugs and restraints were retrieved from resident charts. RESULTS: A
      total of 2292 assessments took place involving 659 residents (1126 control
      measurements, 1166 intervention measurements). The group of residents who
      remained in the intervention condition compared with the group in the control
      condition differed significantly in the CMAI change scores between successive
      assessments [-2.4 CMAI points, 95% confidence interval (CI) -4.3 to -0.6]. No
      significant effects were found for the control-to-intervention group compared
      with the group who remained in the control group (0.0 CMAI points, 95% CI -2.3 to
      2.4). Significant effects were found on 5 of the 12 Neuropsychiatric Inventory
      items and on the use of antipsychotics (odds ratio 0.54, 95% CI 0.37- 0.80) and
      antidepressants (odds ratio 0.65, 95% CI 0.44-0.94). No effect on use of
      restraints was observed. CONCLUSIONS: The Grip on Challenging behavior program
      was able to diminish some forms of challenging behavior and the use of
      psychoactive drugs.

PMID- 24878215
TI  - Management and outcomes of ST-elevation myocardial infarction in nursing home
      versus community-dwelling older patients: a propensity matched study.
AB  - OBJECTIVES: The influence of admission source (nursing home [NH] versus community
      dwelling) on treatment strategies and outcomes among elderly patients with ST
      elevation myocardial infarction (STEMI) has not been investigated. PARTICIPANTS:
      Nationwide Inpatient Sample databases from 2003 to 2010 were used to identify
      270,117 community-dwelling and 4082 NH patients 75 years of age or older with
      STEMI. DESIGN: Retrospective observational study. MEASUREMENTS: Propensity scores
      for admission source were used to assemble a matched cohort of 3081 community
      dwelling and 3132 NH patients, who were balanced on baseline demographic and
      clinical characteristics. Bivariate logistic regression models were then used to
      determine the associations of NH with in-hospital outcomes among matched
      patients. RESULTS: In-hospital mortality was significantly higher in patients
      with STEMI presenting from a NH as compared with community-dwelling patients
      (30.5% versus 27.6%; odds ratio [OR] 1.15, 95% confidence interval [CI] 1.03
      1.29; P = .012). Overall, NH patients were less likely to receive reperfusion
      (thrombolysis, percutaneous coronary intervention, or coronary artery bypass
      grafting) (11.5% versus 13.4%; OR 0.84, 95% CI 0.72-0.98; P = .022). However,
      rates of percutaneous coronary intervention alone were similar in both groups
      (9.9% in NH versus 9.1% in community-dwelling; OR 1.10, 95% CI 0.93-1.30; P =
      .276). Mean length of stay was also similar in both groups (5.68 +/- 5.40 days in
      NH versus 5.69 +/- 4.98 days in community-dwelling, P = .974). CONCLUSION:
      Compared with their community-dwelling counterparts, older NH patients are less
      likely to receive reperfusion therapy for STEMI and have higher in-hospital
      mortality.

PMID- 24878217
TI  - Exciplexes with ionic dopants: stability, structure, and experimental relevance
      of M(+)((2)P)(4)He(n) (M = Sr, Ba).
AB  - M(+)((2)P)(4)Hen species, possibly involved in the post (2)P <- (2)S excitation
      dynamics of Sr(+) and Ba(+) in cold (4)He gas or droplets, are studied employing
      both high level ab initio calculations to determine the potential energy curves
      (PEC) and diffusion Monte Carlo (DMC) to obtain information on their ground state
      structure and energetics. PEC for the excited M(+)((2)P)He dimers were obtained
      using MRCI calculations with extended basis sets. Potential energy surfaces (PES)
      for M(+)((2)P)Hen were built with the DIM model including spin-orbit coupling via
      a perturbative procedure. DMC simulations indicated several exciplexes (n > 2) to
      be stable against He dissociation whatever the ion state, a finding that is at
      variance with what was previously suggested for Ba(+)((2)P1/2) due to the
      repulsive nature of the interaction potential obtained in [ Phys. Rev. A 2004 ,
      69 , 042505 ]. Our results, instead, support the suggestion made in [J. Chem.
      Phys. 2012, 137, 051102] for the existence of Ba(+)((2)P1/2)Hen exciplexes
      emitted following the excitation of the barium cation solvated into He droplets.
      In the (2)P1/2 state, the Ba ion also shows a peculiar behavior as a function of
      n with respect to the location and binding strength of the attached He atoms
      compared to Sr(+). Although the latter forms the usual equatorial He ring, Ba(+)
      deviates from this geometry for 1 <= n <= 4, with the radial distribution
      functions strongly depending on the number of solvent atoms. Finally, a putative
      species is proposed to explain the emission band at 523 nm that follows D1 or D2
      excitation of Ba(+) in superfluid bulk helium.

PMID- 24878216
TI  - Prescription drug use among older adults in Italy: a country-wide perspective.
AB  - In Italy, prescription drug costs represent approximately 17% of total public
      health expenditures. Older adults commonly use multiple drugs and, for this
      reason, this population is responsible for a large portion of drug-related costs.
      In 2012, public expenditure for pharmaceuticals in primary care exceeded 11
      billion Euros (approximately 15.2 billion US $), and older adults aged 65 or
      older accounted for more than 60% of these costs. Recently, increased attention
      has been focused on studies aimed at monitoring drug use and evaluating the
      appropriateness of drug prescribing in older adults. In this article, we examined
      studies that assessed these issues in different settings at a national level.
      Specifically, results of surveys of prescription drug use in primary care
      (OsMED), hospital (GIFA, CRIME, and REPOSI) and long-term care (ULISSE and
      SHELTER) settings are reviewed. Overall, these studies showed that the quality of
      drug prescribing in older patients is far from optimal. This leads to an
      increased risk of negative health outcomes and increased health care costs. Data
      from these studies are valuable, not only to monitor drug use, but also to target
      interventions aimed at improving the quality of prescribing. Translating the
      findings of clinical research and monitoring programs will be challenging, but it
      will lead to quantifiable improvements in the quality of drug prescribing at a
      national level. 

PMID- 24878218
TI  - C-reactive protein level in morbidly obese patients before and after bariatric
      surgery.
AB  - BACKGROUND: Human obesity is associated with a proinflammatory state and an
      elevated level of mediators, such as C-reactive protein (CRP). OBJECTIVES: To
      establish CRP levels as baseline preoperative values and then at 6 months after
      bariatric surgery, as well as to determine the changes in weight, body mass index
      (BMI), leukocytes, and glycemia. MATERIALS AND METHODS: An observational,
      analytical, retrospective, longitudinal, and open study was conducted. Serum CRP
      values were measured in 36 adults presenting with morbid obesity, and their
      baseline relation to weight, BMI, leukocytes, and glycemia was determined; the
      relation to the same parameters was established again, 6 months after bariatric
      surgery. RESULTS: The mean and standard deviation of preoperative and
      postoperative CRP (mg/L) was 1.15+/-0.86 and 0.34+/-0.28, respectively with
      p<0.0001; weight (kg) 112.10+/-22.91 and 84.82+/-17.11, p=0.0443; BMI (kg/m(2))
      42.48+/-5.97 and 32.2+/-4.79, p=0.0988; glucose (mg/dL) 100.58+/-17.82 and
      87.11+/-8.49, p<0.0001, and leukocytes (* 10(3)/mm(3)) 8.62+/-1.69 and 6.99+/
      1.56, p=0.3192. Baseline CRP only correlated with weight and BMI (p=0.047 and
      p=0.027 respectively) and there was no correlation between postoperative CRP and
      the evaluated parameters. CONCLUSIONS: Preoperative CRP had a significant lineal
      relation to weight and body mass index. Patients who underwent bariatric surgery
      had a significant decrease in CRP, weight, and fasting glucose at 6 months after
      surgery.

PMID- 24878219
TI  - Patient satisfaction and quality of life following laparoscopic Nissen
      fundoplication.
AB  - BACKGROUND: Today, antireflux surgery has an established position in the
      management of gastroesophageal reflux disease. Some case series have shown good
      short-term results, but there is still little information regarding long-term
      results. Studies have recently focused on evaluating residual symptomatology and
      its impact on quality of life. OBJECTIVES: To determine the postoperative quality
      of life and degree of satisfaction in patients that underwent laparoscopic Nissen
      fundoplication. PATIENTS AND METHODS: A total of 100 patients (59 women and 41
      men) were studied after having undergone laparoscopic Nissen fundoplication. The
      variables analyzed were level of satisfaction, gastrointestinal quality of life
      index (GIQLI), residual symptoms, and the Visick scale. RESULTS: No variation was
      found in relation to sex; 49 men and 51 women participated in the study. The mean
      age was 49 years. The degree of satisfaction encountered was: satisfactory in 81
      patients, moderate in 3, and bad in 2 patients. More than 90% of the patients
      would undergo the surgery again or recommend it. The Carlsson score showed
      improvement at the end of the study (p<0.05). In relation to the GIQLI, a median
      of 100.61 points+/-21.624 was obtained. Abdominal bloating, regurgitation, and
      early satiety were the most frequent residual symptoms. The effect on lifestyle
      measured by the Visick scale was excellent. CONCLUSIONS: The level of
      satisfaction and quality of life obtained were comparable with reported
      standards; and the residual symptoms after antireflux surgery were easily
      controlled.

PMID- 24878221
TI  - Outcome of trauma patients immobilized by emergency department staff, but not by
      emergency medical services providers: a quality assurance initiative.
AB  - BACKGROUND: Prehospital selective cervical spine immobilization (CSI) is a
      relatively new concept. In our emergency medical services (EMS) system, protocols
      for selective CSI are widely used; yet, some patients who are brought to the
      hospital without CSI undergo secondary immobilization and cervical spine imaging
      in the emergency department (ED). Immobilization in the ED, after a decision not
      to immobilize by EMS, suggests that either the prehospital assessment is not
      trusted or the patient has developed new symptoms over time. We undertook a
      quality assurance initiative to evaluate whether trauma patients brought to the
      ED without CSI, who then underwent secondary CSI and imaging in the ED, had
      injuries that were initially missed by EMS selective CSI protocol. METHODS: This
      was a 36-month retrospective data analysis of blunt trauma patients transported
      directly from the field to the University of New Mexico Hospital level I trauma
      center by Albuquerque Ambulance Service (AAS) between March 2009 and February
      2012. Inclusion criteria were age 18 years and older, transported by AAS without
      CSI, and cervical spinal imaging done in the ED. Patients were excluded if they
      were being transported between facilities, were prisoners, and/or refused CSI. A
      positive finding was defined as any acute abnormality identified by the attending
      radiologist on the final imaging report. RESULTS: The study included 101 patients
      who met inclusion criteria. There were no significant missed injuries. Ninety
      four of the 101 patients received cervical spinal CT imaging at an estimated cost
      of $1,570 per scan, not including physician charges. The remaining patients had
      plain film radiographic imaging. No patients had magnetic resonance imaging.
      CONCLUSIONS: In this retrospective quality assurance initiative, none of 101
      patients who underwent secondary CSI and imaging in the ED had a missed acute
      cervical injury. No patients had any adverse effects or required treatment, yet
      these patients incurred substantial costs and increased radiation exposure. While
      our results suggest hospital personnel should have confidence in prehospital
      decisions regarding CSI, continued surveillance and a large-scale, prospective
      study are needed to confirm our findings.

PMID- 24878220
TI  - Impact of the endoscopic teaching process on colonic adenoma detection.
AB  - BACKGROUND: There has been little reported experience in the Latin American
      hospital setting in relation to the impact of the endoscopic training process on
      colonoscopy quality. AIMS: To determine the effect that training in the technique
      of colonoscopy has on adenoma detection in an Argentinian teaching hospital.
      MATERIAL AND METHOD: Within the time frame of July 2012 and July 2013, 3
      physicians received training in colonoscopy from 4 experienced endoscopists. The
      colonoscopies performed by the supervised trainees were compared with those
      carried out by the experienced endoscopists. RESULTS: A total of 318
      colonoscopies performed by any one of the 3 supervised trainees and 367 carried
      out by any one of the experienced endoscopists were included. The univariate
      analysis showed a non-significant difference in the detection rate of adenomas
      (30.4 vs. 24.7%, P=.09). In the multivariate analysis, the detection rate of
      adenomas was significantly higher in the colonoscopies performed by one of the 3
      trainees (odds ratio = 1.72 [1.19-2.48]). CONCLUSIONS: The supervised involvement
      of endoscopic trainees has a positive effect on adenoma detection.

PMID- 24878222
TI  - Multiparameter optimization in CNS drug discovery: design of pyrimido[4,5
      d]azepines as potent 5-hydroxytryptamine 2C (5-HT2C) receptor agonists with
      exquisite functional selectivity over 5-HT2A and 5-HT2B receptors.
AB  - A series of 4-substituted pyrimido[4,5-d]azepines that are potent, selective 5
      HT2C receptor partial agonists is described. A rational medicinal chemistry
      design strategy to deliver CNS penetration coupled with SAR-based optimization of
      selectivity and agonist potency provided compounds with the desired balance of
      preclinical properties. Lead compounds 17 (PF-4479745) and 18 (PF-4522654)
      displayed robust pharmacology in a preclinical canine model of stress urinary
      incontinence (SUI) and no measurable functional agonism at the key selectivity
      targets 5-HT2A and 5-HT2B in relevant tissue-based assay systems. Utilizing
      recent advances in the structural biology of GPCRs, homology modeling has been
      carried out to rationalize binding and agonist efficacy of these compounds. 

PMID- 24878224
TI  - Nanobubbles within a microbubble: synthesis and self-assembly of hollow manganese
      silicate and its metal-doped derivatives.
AB  - We developed a surface-catalyzed dual templating strategy to synthesize and
      organize hollow spheres of manganese silicate as well as a wide variety of its
      metal-doped structural derivatives (where metal dopant = Fe, Co, Ni, Cu, Y, La,
      Ce, Nd, Eu, Gd, Er, and Yb). The size of hollow spheres obtained is in the range
      of only 7-9 nm. In addition, the resultant nanospheres can also be formed into an
      even greater hollow sphere, giving rise to a "bubbles within a bubble" assemblage
      in the submicrometer regime (e.g., ~200 to 270 nm). The hierarchical hollow
      structures of this type were further tested for catalytic degradation (or
      decomposition) of organic dyes and used as solid precursors for transformative
      synthesis of other silicon-based functional hollow materials. 

PMID- 24878223
TI  - Molecular phylogeny and evolution of the cone snails (Gastropoda, Conoidea).
AB  - We present a large-scale molecular phylogeny that includes 320 of the 761
      recognized valid species of the cone snails (Conus), one of the most diverse
      groups of marine molluscs, based on three mitochondrial genes (COI, 16S rDNA and
      12S rDNA). This is the first phylogeny of the taxon to employ concatenated
      sequences of several genes, and it includes more than twice as many species as
      the last published molecular phylogeny of the entire group nearly a decade ago.
      Most of the numerous molecular phylogenies published during the last 15years are
      limited to rather small fractions of its species diversity. Bayesian and maximum
      likelihood analyses are mostly congruent and confirm the presence of three
      previously reported highly divergent lineages among cone snails, and one
      identified here using molecular data. About 85% of the species cluster in the
      single Large Major Clade; the others are divided between the Small Major Clade
      (~12%), the Conus californicus lineage (one species), and a newly defined clade
      (~3%). We also define several subclades within the Large and Small major clades,
      but most of their relationships remain poorly supported. To illustrate the
      usefulness of molecular phylogenies in addressing specific evolutionary
      questions, we analyse the evolution of the diet, the biogeography and the toxins
      of cone snails. All cone snails whose feeding biology is known inject venom into
      large prey animals and swallow them whole. Predation on polychaete worms is
      inferred as the ancestral state, and diet shifts to molluscs and fishes occurred
      rarely. The ancestor of cone snails probably originated from the Indo-Pacific;
      rather few colonisations of other biogeographic provinces have probably occurred.
      A new classification of the Conidae, based on the molecular phylogeny, is
      published in an accompanying paper. 

PMID- 24878225
TI  - Mapping single molecular binding kinetics of carbohydrate-binding module with
      crystalline cellulose by atomic force microscopy recognition imaging.
AB  - We studied the binding kinetics of family 3 carbohydrate-binding module (CBM3a)
      molecules to crystalline cellulose fibrils extracted from the poplar cell wall by
      atomic force microscopy (AFM) recognition imaging. The free CBM3a molecules of
      different concentrations were added to the buffer solution to bind to the
      crystalline cellulose sample immobilized on the AFM substrate. During in-situ AFM
      imaging, the CBM molecules were observed to bind to cellulose efficiently and
      regularly, especially in the first 60-120 min. A 1:1 single-molecule binding
      model was used to study the kinetics of the CBM3a-cellulose interaction. The
      saturation time when the concentration of occupied binding sites is 99% of the
      maximum bound CBM3a concentration at the end of reaction, t(0.99), was determined
      by fitting different concentrations of CBM3a against reaction time using the high
      resolution AFM images and the single-molecule kinetics equations. Based on the
      experimental data and kinetics calculations, the minimal effective initial CBM3a
      concentration was estimated to be 5.1 * 10(-7) M at 287 min reaction time. This
      study provides an in-depth understanding of the binding mechanism of CBM with
      crystalline cellulose at single molecule level. 

PMID- 24878226
TI  - A novel locus for a hereditary recurrent neuropathy on chromosome 21q21.
AB  - Hereditary recurrent neuropathies are uncommon. Disorders with a known molecular
      basis falling within this group include hereditary neuropathy with liability to
      pressure palsies (HNPP) due to the deletion of the PMP22 gene or to mutations in
      this same gene, and hereditary neuralgic amyotrophy (HNA) caused by mutations in
      the SEPT9 gene. We report a three-generation family presenting a hereditary
      recurrent neuropathy without pathological changes in either PMP22 or SEPT9 genes.
      We performed a genome-wide mapping, which yielded a locus of 12.4 Mb on
      chromosome 21q21. The constructed haplotype fully segregated with the disease and
      we found significant evidence of linkage. After mutational screening of genes
      located within this locus, encoding for proteins and microRNAs, as well as
      analysis of large deletions/insertions, we identified 71 benign polymorphisms.
      Our findings suggest a novel genetic locus for a recurrent hereditary neuropathy
      of which the molecular defect remains elusive. Our results further underscore the
      clinical and genetic heterogeneity of this group of neuropathies.

PMID- 24878227
TI  - The decreased expression of thioredoxin-1 in brain of mice with experimental
      autoimmune myasthenia gravis.
AB  - Myasthenia gravis (MG) is an autoimmune disease caused by circulating antibodies
      that block acetylcholine receptor (AchR) at the neuromuscular junction. There is
      the cognitive and memory impairment in patients with MG. However, the molecular
      mechanisms underlying the alteration of central nervous system in MG remain
      unknown. In the present study, we found that the level of malondialdehyde (MDA)
      was increased in the brain of experimental autoimmune myasthenia gravis (EAMG).
      Furthermore, the expression of thioredoxin-1 (Trx-1) and the activity of cAMP
      response element-binding protein (CREB) were significantly decreased in frontal
      lobe and hippocampus of mice with EAMG. We also found that the expression of pro
      apoptotic C/EBP homologous protein (CHOP) was increased in the frontal lobe and
      hippocampus of mice. However, the expressions of glucose regulated protein 78
      (GRP78/Bip) was not changed in same areas. Inversely, the expressions of pro
      caspase-12, pro-caspase-3 and pro-caspase-9 were decreased. These data indicate
      that Trx-1 mediated endoplasmic reticulum and mitochondria pathways are involved
      in brain damage in MG. Trx-1 may be a pivotal target for brain protective
      treatment in MG. 

PMID- 24878228
TI  - Characteristics of muscle cramps in patients with polyneuropathy.
AB  - Muscle cramps are common in the general population and can be disabling for
      patients, but there is little evidence comprehensively evaluating cramp
      characteristics in patients with polyneuropathy. This study describes the
      prevalence and characteristics of muscle cramps in this patient group. Patients
      over 18 diagnosed with polyneuropathy were invited to join the study. Patients
      completed nerve conduction studies, the Toronto Clinical Neuropathy score,
      neuropathy-specific Vickrey's Quality of Life Assessment and a self-administered
      questionnaire examining demographics, neuropathy symptoms and cramp
      characteristics. Two hundred and twenty-five participants were enrolled (28.0%
      female). Sixty-three percent of patients experienced cramps, occurring on average
      6 times per week, lasting 10.5 min and scoring 6 out of 10 on a pain scale and
      described as disabling by 43.6% of patients. No significant difference was found
      in cramp prevalence according to underlying pathophysiology (p = 0.52) or fiber
      type (p = 0.41). Patients with disabling cramps rated their physical (p < 0.0001)
      and mental (p = 0.04) quality of life lower than patients without disabling
      cramps. This study confirms that muscle cramps are common, disabling and
      associated with reduced quality of life in patients with polyneuropathy. Similar
      prevalence of cramps across predominant nerve fiber type suggests a role of
      sensory afferents in cramp generation, although this needs to be confirmed in
      larger cohorts.

PMID- 24878229
TI  - Whole exome sequencing identifies three recessive FIG4 mutations in an apparently
      dominant pedigree with Charcot-Marie-Tooth disease.
AB  - Charcot-Marie-Tooth disease (CMT) is genetically heterogeneous and classification
      based on motor nerve conduction velocity and inheritance is used to direct
      genetic testing. With the less common genetic forms of CMT, identifying the
      causative genetic mutation by Sanger sequencing of individual genes can be time
      consuming and costly. Next-generation sequencing technologies show promise for
      clinical testing in diseases where a similar phenotype is caused by different
      genes. We report the unusual occurrence of CMT4J, caused by mutations in FIG4, in
      a apparently dominant pedigree. The affected proband and her mother exhibit
      different disease severities associated with different combinations of compound
      heterozygous FIG4 mutations, identified by whole exome sequencing. The proband
      was also shown to carry a de novo nonsense mutation in the dystrophin gene, which
      may contribute to her more severe phenotype. This study is a cautionary reminder
      that in families with two generations affected, explanations other than dominant
      inheritance are possible, such as recessive inheritance due to three mutations
      segregating in the family. It also emphasises the advantages of next-generation
      sequencing approaches that screen multiple CMT genes at once for patients in whom
      the common genes have been excluded. 

PMID- 24878230
TI  - Evidence that birth weight is decreased by maternal lead levels below 5MUg/dl in
      male newborns.
AB  - To assess the association between birth weight and maternal blood lead (BPb)
      levels, 386 pregnant women and their newborn offspring were surveyed. Mean+/-SD
      (range) maternal BPb concentrations were 0.98+/-0.55 (0.10-3.99), 0.92+/-0.63
      [<0.09 (limit of quantification)-3.96], and 0.99+/-0.66 (<0.09-3.96)MUg/dl at 12,
      25 and 36 weeks' gestation, respectively. Mean+/-SD (range) gestational age at
      delivery was 38.9+/-1.3 (35-41) weeks. In male newborns, a significant
      correlation between birth weight and logBPb at 12 weeks' gestation was observed
      (Spearman's rank correlation coefficient=-0.145, p<0.05). Multiple regression
      analysis indicated that birth weight was significantly inversely associated with
      logBPb at 12 weeks' gestation, controlling for possible confounding variables.
      These results suggest that low-level exposure to lead in early gestation could be
      a risk factor for reduced birth weight in male offspring. 

PMID- 24878231
TI  - Response to 'Re. Outcomes after open repair for ruptured abdominal aortic
      aneurysms in patients with friendly versus hostile aortoiliac anatomy'.

PMID- 24878232
TI  - Re: "Outcome after open repair for ruptured abdominal aortic aneurysms in
      patients with friendly versus hostile aortoiliac anatomy".

PMID- 24878233
TI  - Commentary on 'carotid artery atherosclerosis among 65-year-old Swedish men: a
      population based screening study'.

PMID- 24878235
TI  - Endograft limb occlusion in EVAR: iliac tortuosity quantified by three different
      indices on the basis of preoperative CTA.
AB  - OBJECTIVE: To assess the incidence and outcome of graft limb occlusions after
      endovascular aortic repair (EVAR) of abdominal aortic aneurysm (AAA) in a high
      volume single centre. To quantify iliac artery tortuosity in patients with AAA
      and correlate this with limb occlusion. DESIGN: Data were collected consecutively
      and prospectively, and analyzed retrospectively. MATERIALS: Patients treated with
      Zenith bifurcated stent grafts from January 2000 to December 2010 at a tertiary
      referral vascular unit were analyzed. Routine regular office follow-up with
      computed tomography angiography (CTA) and, subsequently, duplex ultrasound
      imaging was performed. Patients with limb occlusions were identified. For each
      index patient, two controls were obtained, one immediately preceding and one
      following the index patient in the consecutive cohort of EVAR patients. METHODS:
      Demographics and CTA data on limb graft occlusions were recorded and compared
      with a defined control group. Three different indices were used to describe the
      tortuosity of the iliac vessels based on preoperative CTA: pelvic artery index of
      tortuosity (PAI), common iliac artery index of tortuosity (CAI), and a visual
      description of vessel tortuosity - the double iliac sign (DIS). Demographic data
      and indices were correlated for later occurring limb occlusion. RESULTS: 504
      patients underwent EVAR and 18 patients experienced graft limb occlusion during a
      median follow-up of 28 months (range 0-133). Primary graft patency was 97% at 1
      year and 96% at 3 years. Logistic regression showed that iliac artery tortuosity
      (DIS) (p = .001) and body mass index (p = .007) had a significant impact on graft
      patency. CONCLUSION: A tortuous vessel on the preoperative CTA is associated with
      an increased risk of limb occlusion after EVAR. Adjunctive stenting of iliac
      segments deemed at risk is suggested, which is achieved without compromise of the
      aneurysm repair.

PMID- 24878234
TI  - Real-world performance of the new C3 Gore Excluder stent-graft: 1-year results
      from the European C3 module of the Global Registry for Endovascular Aortic
      Treatment (GREAT).
AB  - OBJECTIVES: The European C3 module of the Global Registry for Endovascular Aortic
      Treatment (GREAT) provides "real-world" outcomes for the new C3 Gore Excluder
      stent-graft, and evaluates the new deployment mechanism. This report presents the
      1-year results from 400 patients enrolled in this registry. METHODS: Between
      August 2010 and December 2012, 400 patients (86.8% male, mean age 73.9 +/- 7.8
      years) from 13 European sites were enrolled in this registry. Patient
      demographics, treatment indication, case planning, operative details including
      repositioning and technical results, and clinical outcome were analyzed. RESULTS:
      Technical success was achieved in 396/400 (99%) patients. Two patients needed
      intraoperative open conversion, one for iliac rupture, the second because the
      stent-graft was pulled down during a cross-over catheterization in an angulated
      anatomy. Two patients required an unplanned chimney renal stent to treat partial
      coverage of the left renal artery because of upward displacement of the stent
      graft. Graft repositioning occurred in 192/399 (48.1%) patients, most frequently
      for level readjustment with regard to the renal arteries, and less commonly for
      contralateral gate reorientation. Final intended position of the stent-graft
      below the renal arteries was achieved in 96.2% of patients. Thirty-day mortality
      was two (0.5%) patients. Early reintervention (<=30 days) was required in two
      (0.5%) patients. Mean follow-up duration was 15.9 +/- 8.8 months (range 0-37
      months). Late reintervention (>30 days) was required in 26 (6.5%) patients.
      Estimated freedom from reintervention at 1 year was 95.2% (95% CI 92.3-97%), and
      at 2 years 91.5% (95% CI 86.8-94.5%). Estimated patient survival at 1 year was
      96% (95% CI 93.3-97.6%) and at 2 years 90.6% (95% CI 85.6-93.9%). CONCLUSIONS:
      Early real-world experience shows that the new C3 delivery system offers
      advantages in terms of device repositioning resulting in high deployment
      accuracy. Longer follow-up is required to confirm that this high deployment
      accuracy results in improved long-term durability.

PMID- 24878236
TI  - Change in smoking habits after having been screened for abdominal aortic
      aneurysm.
AB  - OBJECTIVES: To study smoking habits among men with abdominal aortic aneurysm at
      screening at 65 years of age, and during follow-up, as a base-line study to
      evaluate future interventions. DESIGN: Nested case-control study. PATIENTS AND
      METHODS: Between 2006 and 2011, 8150 65-year-old men (compliance 85%) were
      screened for AAA in Uppsala County, Sweden. Among 292 men with an aortic diameter
      of at least 25 mm, 77 were active smokers at the time of screening. At follow-up
      of smoking habits in 2012, 53 men (69%) participated in this study, 28 had an AAA
      of at least 30 mm and 25 a sub-aneurysmal aorta (SAA) 25-29 mm at baseline. For
      each case, one control was randomly selected, all active smokers with aortic
      diameter less than 25 mm at baseline, matched for age and year of screening.
      Telephone interviews were performed at a median 34 months (range: 4-67) after
      screening. RESULTS: Men with AAA had hypertension more often than controls (68%
      vs. 23%, p < .001). Men with AAA and SAA reported more smoking years than
      controls (p = .017). Cessation rate among patients with AAA did not differ
      significantly compared with men with an aorta less than 30 mm (29% vs. 15%, p =
      .159), but they had reduced their consumption of cigarettes/day significantly
      more than men with SAA and controls (-8.2 vs. -3.0 vs. -4.5, p = .030). Men with
      AAA recalled having been informed about the importance of smoking cessation at
      the time of screening more often (p = .031). There was no difference in growth of
      the AAA between those who continued, and those who quit smoking (2.03 vs. 2.01
      mm/year, p = .982), but the study was not powered to study AAA growth.
      CONCLUSIONS: Although counselling in a normal healthcare setting had some effect,
      the results indicate a need to tailor interventions to further increase smoking
      cessation rates among men diagnosed with both AAA and SAA.

PMID- 24878237
TI  - Percutaneous vascular closure using an anchored collagen plug provides effective
      haemostasis following both antegrade and retrograde femoral arterial punctures.
AB  - OBJECTIVES: Small published series suggest a higher failure rate for Angio-Seal
      vascular closure device (VCD) deployment after antegrade femoral puncture,
      despite the need for shorter haemostasis times, early discharge, and possibly
      higher turnover. We seek to compare the deployment efficacy and complications of
      the Angio-Seal VCD between antegrade and retrograde femoral arterial deployments.
      METHODS: Radiological data was retrospectively analysed from prospective
      databases from the hospitals' Computerised Radiology Information System (CRIS)
      over 2010-2012. Angio-Seal gauge, Rutherford class (as applicable), puncture mode
      (used to classify deployment as antegrade/retrograde), sheath sizes, and
      deployment success/failures were recorded. Numerical/statistical analyses were
      undertaken using Microsoft Excel 10/SISA software. RESULTS: A total of 519 Angio
      Seal VIP VCDs were deployed in 470 patients over 2010-2012 (13 other patients
      could not be analysed due to incomplete data). Sheath sizes for
      antegrade/retrograde femoral puncture were 5F, n = 22/9; 6F, n = 244/223; 7F, n =
      1/5; 9F, n = 4/0. 8F Angio-Seal VIPs were used for 9F punctures only, 6F for the
      remainder. The overall deployment success rate was 93.7%. In total, 247 (91.1%)
      successful antegrade deployments were undertaken with 24 (8.9%) failures,
      compared with 229 (96.6%) successful retrograde deployments with eight (3.4%)
      failures. Antegrade/retrograde failures were classed as failure to deploy, n =
      15/5; bleeding despite successful deployment requiring supplementary compression,
      n = 6/1; haematoma formation, n = 2/1; groin pain, n = 0/1; vessel stenosis, n =
      1/0. Higher deployment failures were noted with antegrade deployment (p < .02,
      chi-square test). CONCLUSIONS: Angio-Seal deployment is successful for both
      antegrade/retrograde femoral punctures albeit with a higher antegrade failure
      rate.

PMID- 24878238
TI  - The use of a vanadium species as a catalyst in photoinduced water oxidation.
AB  - The first water oxidation catalyst containing only vanadium atoms as metal
      centers is reported. The compound is the mixed-valence [(V(IV)5V(V)1)O7(OCH3)12](
      ) species, 1. Photoinduced water oxidation catalyzed by 1, in the presence of
      Ru(bpy)3(2+) (bpy = 2,2'-bipyridine) and Na2S2O8, in acetonitrile/aqueous
      phosphate buffer takes place with a quantum yield of 0.20. A hole scavenging
      reaction between the photochemically generated Ru(bpy)3(3+) and 1 occurs with a
      bimolecular rate constant of 2.5 * 10(8) M(-1) s(-1). The time-resolved formation
      of the oxidized molecular catalyst 1(+) in bimolecular reactions is also
      evidenced for the first time by transient absorption spectroscopy. This result
      opens the way to the use of less expensive vanadium clusters as water oxidation
      catalysts in artificial photosynthesis schemes. 

PMID- 24878239
TI  - Acute and subchronic toxicity of arprinocid in Sprague-Dawley rats.
AB  - We subjected Sprague-Dawley rats to an acute and 13-week subchronic oral toxicity
      of arprinocid, a nucleoside analogue used as a coccidiostat, according to
      toxicological guidelines as part of its safety assessment. In the acute study,
      arprinocid was administered once by oral gavage to rats at doses ranging from
      292.4 to 506.0mg/kgb.w. The calculated LD50 was 442.9mg/kgb.w. in males and
      378.7mg/kgb.w. in females. In the subchronic study, male and female rats were fed
      with diets supplemented with 0, 25, 187.5 or 500ppm arprinocid for 13weeks.
      Significantly lower body weights were noted in the 500ppm group females. The mean
      body weights of the 500ppm group females were 12.9% lower than that of the
      controls. Significant differences in haematological and biochemical parameters as
      well as organ weights were detected between the 500 and 187.5ppm groups.
      Histopathological observations revealed that 500 and 187.5ppm arprinocid could
      induce hepatic steatosis and focal hepatocellular necrosis. Slight protein cast
      in some renal tubules and tubular regeneration were observed in the high dose
      group of both genders. The dietary no-observed-adverse-effect level (NOAEL) of
      arprinocid in rats for 13weeks is 25ppm (approximately 1.7mg/kgb.w./day).

PMID- 24878240
TI  - Pre-clinical toxicokinetics and safety study of M2ES, a PEGylated recombinant
      human endostatin, in rhesus monkeys.
AB  - PEGylated recombinant human endostatin (M2ES) exhibited prolonged serum half-life
      and enhanced antitumor activity when compared with endostatin. A non-clinical
      study was performed to evaluate the toxicokinetics and safety of M2ES in rhesus
      monkeys. After intravenous (IV) infusions of M2ES at a dose level of 3, 10, and
      30mg/kg in rhesus monkeys, the concentration-time curves of M2ES were best fitted
      to a non-compartment model, and area under the curve (AUC) was positively
      correlated with the dosage. M2ES had a tendency to accumulate in vivo following
      successive IV infusions. Serum anti-M2ES IgG antibodies were generated quickly
      during IV administration, and the antibody level in serum did not significantly
      decrease after four-week recovery period. Animals administered IV infusions twice
      weekly (M2ES at 10 or 30mg/kg body weight per day) for 3months developed mild or
      moderate vacuolation of proximal tubule epithelial cell in proximal convoluted
      tubule of kidney, but this adverse-effect was reversible. In summary, M2ES was
      well tolerated and did not cause any serious toxicity. These pre-clinical safety
      data contribute to the initiation of the ongoing clinical study.

PMID- 24878242
TI  - Memantine prevents reference and working memory impairment caused by sleep
      deprivation in both young and aged Octodon degus.
AB  - Memory loss is one of the key features of cognitive impairment in either aging,
      Mild Cognitive Impairment (MCI) or dementia. Pharmacological treatments for
      memory loss are today focused on addressing symptomatology. One of these approved
      compounds is memantine, a partial NMDA receptor antagonist that has proved its
      beneficial effects in cognition. The Octodon degus (O. degus) has been recently
      proposed as a potential model relevant for neurodegenerative diseases. However,
      there are no previous studies investigating the effect of pharmacological
      treatments for age-related cognitive impairment in this rodent. In this work we
      aimed to evaluate the effect of memantine on sleep deprivation (SD)-induced
      memory impairment in young and old O. degus. Young and old animals were trained
      in different behavioral paradigms validated for memory evaluation, and randomly
      assigned to a control (CTL, n=14) or an SD (n=14) condition, and treated with
      vehicle or memantine (10-mg/Kg i.p.) before the SD started. We demonstrate that
      SD impairs memory in both young and old animals, although the effect in the old
      group was significantly more severe (P<0.05). Memantine pretreatment was able to
      prevent the cognitive impairment caused by SD in both age groups, while it had no
      negative effect on CTL animals. The positive effect of memantine in counteracting
      the negative effect of SD on the retrieval process even in the aged O. degus
      further supports the translational potential of both the challenge and the
      species, and will enable a better understanding of the behavioral features of
      memantine effects, especially related with reference and working memories.

PMID- 24878241
TI  - Functional insight into development of positive allosteric modulators of AMPA
      receptors.
AB  - Positive allosteric modulators of alpha-amino-3-hydroxy-5-methyl-isoxazole
      propionic acid (AMPA) ionotropic glutamate receptors facilitate synaptic
      plasticity and contribute essentially to learning and memory, properties which
      make AMPA receptors targets for drug discovery and development. One region at
      which several different classes of positive allosteric modulators bind lies at
      the dimer interface between the ligand-binding core of the second, membrane
      proximal, extracellular domain of AMPA receptors. This solvent-accessible binding
      pocket has been the target of drug discovery efforts, leading to the recent
      delineation of five "subsites" which differentially allow access to modulator
      moieties, and for which distinct modulator affinities and apparent efficacies are
      attributed. Here we use the voltage-clamp technique in conjunction with rapid
      drug application to study the effects of mutants lining subsites "A" and "B" of
      the allosteric modulator pocket to assess affinity and efficacy of allosteric
      modulation by cyclothiazide, CX614, CMPDA and CMPDB. A novel analysis of the
      decay of current produced by the onset of desensitization has allowed us to
      estimate both affinity and efficacy from single concentrations of modulator. Such
      an approach may be useful for effective high throughput screening of new target
      compounds. 

PMID- 24878243
TI  - Inhibition of the microglial response is essential for the neuroprotective
      effects of Rho-kinase inhibitors on MPTP-induced dopaminergic cell death.
AB  - Several recent studies have shown that activation of the RhoA/Rho-associated
      kinase (ROCK) pathway is involved in the MPTP-induced dopaminergic cell
      degeneration and possibly in Parkinson's disease. ROCK inhibitors have been
      suggested as candidate neuroprotective drugs for Parkinson's disease. However,
      the mechanism responsible for the increased survival of dopaminergic neurons
      after treatment with ROCK inhibitors is not clear. We exposed primary (neuron
      glia) mesencephalic cultures, cultures of the MES 23.5 dopaminergic neuron cell
      line and primary mesencephalic cultures lacking microglial cells to the
      dopaminergic neurotoxin MPP+ and the ROCK inhibitor Y-27632 in order to study the
      effects of ROCK inhibition on dopaminergic cell loss and the length of neurites
      of surviving dopaminergic neurons. In primary (neuron-glia) cultures,
      simultaneous treatment with MPP+ and the ROCK inhibitor significantly reduced the
      loss of dopaminergic neurons. In the absence of microglia, treatment with the
      ROCK inhibitor did not induce a significant reduction in the dopaminergic cell
      loss. Treatment with the ROCK inhibitor induced a significant decrease in axonal
      retraction in primary cultures with and without microglia and in cultures of the
      MES 23.5 neuron cell line. In conclusion, inhibition of microglial ROCK is
      essential for the neuroprotective effects of ROCK inhibitors against cell death
      induced by the dopaminergic neurotoxin MPP+. In addition, ROCK inhibition induced
      a direct effect against axonal retraction in surviving neurons. However, the
      latter effect was not sufficient to cause a significant increase in the survival
      of dopaminergic neurons after treatment with MPP+.

PMID- 24878245
TI  - Ginsenosides attenuate methylglyoxal-induced impairment of insulin signaling and
      subsequent apoptosis in primary astrocytes.
AB  - Diabetes mellitus (DM), which is characterized by chronic hyperglycemia, is known
      to increase the risk of neurodegeneration. In type 2 diabetes, hyperglycemia
      could cause insulin resistance and neurodegeneration in various cells including
      neurons and astrocytes. Hyperglycemia is also known to result in the formation of
      advanced glycation end-products (AGE) Methylglyoxal (MG) is one of the most
      reactive AGE precursors in which its abnormal accumulation is usually found in
      diabetic patients and induces neuronal cell death in central nervous system.
      Ginseng is a herb that has been widely used to treat various diseases in
      traditional Chinese medicine. Ginsenosides, the pharmacologically active
      component isolated from ginseng, have been shown to have cryoprotective effects
      in different neural cells. In the present study we investigated the effects of MG
      in disturbing insulin signaling and leading to further cellular apoptosis in rat
      primary astrocytes. Furthermore, the protective effects of different subtypes of
      ginsenosides were studied. From the results, impairment of insulin signaling was
      found in astrocytes under MG treatment. Moreover, cleavage of caspase and Poly
      ADP ribose polymerase (PARP) was observed in line with insulin signaling
      disruption, showing the neurotoxic effects of MG towards astrocytes. The effects
      of ginsenosides in MG treated astrocytes were also investigated. After treatment,
      ginsenosides Rd and R-Rh2 were shown to ameliorate the cell viability of MG
      treated astrocytes. In addition, Rd and R-Rh2 could improve insulin signaling and
      inhibit apoptosis, indicating that Rd, R-Rh2 and related compounds may have
      therapeutic potential in treating diabetes-induced neurodegeneration. 

PMID- 24878246
TI  - Infrared spectra and electronic structure calculations for NN complexes with U,
      UN, and NUN in solid argon, neon, and nitrogen.
AB  - Reactions of laser-ablated U atoms with N2 molecules upon codeposition in excess
      argon or neon at 4 K gave intense NUN and weak UN absorptions. Annealing produced
      progressions of new absorptions for the UN2(N2)1,2,3,4,5 and UN(N2)1,2,3,4,5,6
      complexes. The neon-to-argon matrix shift decreases with increasing NN ligation
      and therefore the number of noble gas atoms left in the primary coordination
      sphere around the NUN molecule. Small matrix shifts are observed when the
      secondary coordination layers around the primary UN2(N2)1,2,3,4,5 and
      UN(N2)1,2,3,4,5,6 complexes are changed from neon-to-argon to nitrogen.
      Electronic structure, energy, and frequency calculations provide support for the
      identification of these complexes and the characterization of the N=U=N and U=N
      core molecules as terminal uranium nitrides. Codeposition of U with pure nitrogen
      produced the saturated U(NN)7 complex, which UV irradiation converted to the
      NUN(NN)5 complex with slightly lower frequencies than found in solid argon. 

PMID- 24878244
TI  - Different oxysterols have opposing actions at N-methyl-D-aspartate receptors.
AB  - Oxysterols have emerged as important biomarkers in disease and as signaling
      molecules. We recently showed that the oxysterol 24(S)-hydroxycholesterol, the
      major brain cholesterol metabolite, potently and selectively enhances NMDA
      receptor function at a site distinct from other modulators. Here we further
      characterize the pharmacological mechanisms of 24(S)-hydroxycholesterol and its
      synthetic analog SGE201. We describe an oxysterol antagonist of this positive
      allosteric modulation, 25-hydroxycholesterol. We found that 24(S)
      hydroxycholesterol and SGE201 primarily increased the efficacy of NMDAR agonists
      but did not directly gate the channel or increase functional receptor number.
      Rather than binding to a direct aqueous-accessible site, oxysterols may partition
      into the plasma membrane to access the NMDAR, likely explaining slow onset and
      offset kinetics of modulation. Interestingly, oxysterols were ineffective when
      applied to the cytosolic face of inside-out membrane patches or through a whole
      cell pipette solution, suggesting a non-intracellular site. We also found that
      another natural oxysterol, 25-hydroxycholesterol, although exhibiting slight
      potentiation on its own, non-competitively and enantioselectively antagonized the
      effects of 24(S)-hydroxycholesterol analogs. In summary, we suggest two novel
      allosteric sites on NMDARs that separately modulate channel gating, but together
      oppose each other. 

PMID- 24878247
TI  - Role of notch signaling in the maintenance of human mesenchymal stem cells under
      hypoxic conditions.
AB  - Human adipose tissue-derived multilineage progenitor cells (hADMPCs) are
      attractive for cell therapy and tissue engineering because of their multipotency
      and ease of isolation without serial ethical issues. However, their limited in
      vitro lifespan in culture systems hinders their therapeutic application. Some
      somatic stem cells, including hADMPCs, are known to be localized in hypoxic
      regions; thus, hypoxia may be beneficial for ex vivo culture of these stem cells.
      These cells exhibit a high level of glycolytic metabolism in the presence of high
      oxygen levels and further increase their glycolysis rate under hypoxia. However,
      the physiological role of glycolytic activation and its regulatory mechanisms are
      still incompletely understood. Here, we show that Notch signaling is required for
      glycolysis regulation under hypoxic conditions. Our results demonstrate that 5%
      O2 dramatically increased the glycolysis rate, improved the proliferation
      efficiency, prevented senescence, and maintained the multipotency of hADMPCs.
      Intriguingly, these effects were not mediated by hypoxia-inducible factor (HIF),
      but rather by the Notch signaling pathway. Five percent O2 significantly
      increased the level of activated Notch1 and expression of its downstream gene,
      HES1. Furthermore, 5% O2 markedly increased glucose consumption and lactate
      production of hADMPCs, which decreased back to normoxic levels on treatment with
      a gamma-secretase inhibitor. We also found that HES1 was involved in induction of
      GLUT3, TPI, and PGK1 in addition to reduction of TIGAR and SCO2 expression. These
      results clearly suggest that Notch signaling regulates glycolysis under hypoxic
      conditions and, thus, likely affects the cell lifespan via glycolysis. 

PMID- 24878250
TI  - Social network drinking and family history contribute equally to first-onset
      alcohol dependence in high risk adults.
AB  - BACKGROUND: Adult alcohol consumption is influenced by peer consumption, but
      whether peer drinking is associated with first-onset alcohol dependence (AD) in
      adults after age 30 is unknown. METHODS: 703 adult participants in the St. Louis
      Epidemiologic Catchment Area Survey (ECA) with no prior history of AD, but with
      high risk based on previously reported drinking or family history, were re
      interviewed 11 years after the last ECA assessment to detect new cases of AD (age
      at follow-up: M(S.D.)=42.9 (8.2)). Incident AD during the assessment interval was
      examined in relation to drinking patterns in the social network and history of
      alcohol problems in parents. RESULTS: Fifteen percent of the sample had a first
      onset of AD; another 19.5% never developed AD but were high-risk drinkers at
      follow-up. Of those who developed AD, 32.1% were remitted and 67.9% were
      unremitted (current AD) or unstably remitted (asymptomatic high-risk drinkers).
      Compared to abstinent or low-risk drinkers who did not develop AD, high-risk
      drinkers with no AD and unremitted/unstably remitted individuals were 4 times as
      likely to report moderate drinkers in their networks and remitted individuals
      were nearly 3 times as likely to report network members in recovery from alcohol
      problems. Associations of social network drinking with remitted and current AD
      were similar in strength to those of parental alcohol problems. CONCLUSIONS:
      Social network drinking patterns are associated with high-risk drinking and with
      the development of incident AD in adults, with effects equal to that of alcohol
      problems in both parents.

PMID- 24878248
TI  - Cocaine behavioral economics: from the naturalistic environment to the controlled
      laboratory setting.
AB  - BACKGROUND: We previously observed that behavioral economic factors predict
      naturalistic heroin seeking behavior that correlates with opioid seeking in the
      experimental laboratory. The present study sought to replicate and extend these
      prior findings with regular cocaine users. METHODS: Participants (N=83) completed
      a semi-structured interview to establish income-generating and cocaine
      purchasing/use repertoire during the past month. Questions addressed
      sources/amounts of income and expenditures; price (money and time) per purchase;
      and frequency/amounts of cocaine purchased and consumed. Naturalistic cocaine
      purchasing and use patterns were: (1) analyzed as a function of income quartile,
      (2) perturbed by hypothetical changes in cost factors to assess changes in
      purchasing/use habits, and (3) correlated with experimental cocaine seeking.
      RESULTS: Income was positively related to naturalistic cocaine seeking/use
      pattern (i.e., income elastic), and behaviors were cost-efficient and sensitive
      to supply chain. Income was unrelated to proportional expenditure on cocaine
      (~55%) but inversely related to food expenditure. In all hypothetical scenarios
      (changes in income or dealer, loss of income assistance from government or
      family/friends, and increasing arrest risk when purchasing), the high-income
      group reported they would continue to use more cocaine daily than other groups.
      Number of laboratory cocaine choices significantly correlated with cocaine
      purchase time (positively) and purity of cocaine (negatively) in the naturalistic
      setting. CONCLUSIONS: These results replicate and extend findings with regular
      heroin users, demonstrate the importance of income, cost-efficiency and supply
      mindedness in cocaine seeking/use, and suggest that this interview-based approach
      has good external validity.

PMID- 24878252
TI  - Comparative abilities of Microsoft Kinect and Vicon 3D motion capture for gait
      analysis.
AB  - Biomechanical analysis is a powerful tool in the evaluation of movement
      dysfunction in orthopaedic and neurologic populations. Three-dimensional (3D)
      motion capture systems are widely used, accurate systems, but are costly and not
      available in many clinical settings. The Microsoft KinectTM has the potential to
      be used as an alternative low-cost motion analysis tool. The purpose of this
      study was to assess concurrent validity of the KinectTM with Brekel Kinect
      software in comparison to Vicon Nexus during sagittal plane gait kinematics.
      Twenty healthy adults (nine male, 11 female) were tracked while walking and
      jogging at three velocities on a treadmill. Concurrent hip and knee peak flexion
      and extension and stride timing measurements were compared between Vicon and
      KinectTM. Although Kinect measurements were representative of normal gait, the
      KinectTM generally under-estimated joint flexion and over-estimated extension.
      KinectTM and Vicon hip angular displacement correlation was very low and error
      was large. KinectTM knee measurements were somewhat better than hip, but were not
      consistent enough for clinical assessment. Correlation between KinectTM and Vicon
      stride timing was high and error was fairly small. Variability in KinectTM
      measurements was smallest at the slowest velocity. The KinectTM has basic motion
      capture capabilities and with some minor adjustments will be an acceptable tool
      to measure stride timing, but sophisticated advances in software and hardware are
      necessary to improve KinectTM sensitivity before it can be implemented for
      clinical use.

PMID- 24878249
TI  - The effects of social learning on the acquisition of cocaine self-administration.
AB  - BACKGROUND: Social learning models of substance use propose that drug-use
      behaviors are learned by observing and mimicking the behavior of others. The aim
      of this study was to examine the acquisition of cocaine self-administration in
      three groups of experimentally naive rats: rats that were tested in isolation,
      rats that were tested in the presence of another rat that had access to cocaine
      and had previously been trained to self-administer cocaine, and rats that were
      tested in the presence of another rat that did not have access to cocaine.
      METHODS: Male rats were reared in isolated or pair-housed conditions and
      implanted with intravenous catheters. Pair-housed rats were then assigned to drug
      experienced or drug-naive conditions. In the drug-experienced condition, one rat
      of each pair was trained to self-administer cocaine in isolation before the
      reintroduction of its partner. In the drug-naive condition, one rat of each pair
      did not have access to cocaine for the duration of the study. For each group, the
      acquisition of cocaine self-administration was measured over 15 days in rats with
      access to cocaine but no prior operant training. RESULTS: Rats tested with a drug
      experienced partner were faster to acquire cocaine self-administration and
      emitted more active lever presses than rats tested with a cocaine-naive partner.
      Data for the isolated control group fell between the other two groups on these
      measures. CONCLUSION: These data indicate that the acquisition of cocaine self
      administration can either be facilitated or inhibited by social contact.
      Collectively, these results support a social learning model of substance use.

PMID- 24878253
TI  - Hypertensive response to exercise in dipper and non-dipper normotensive
      diabetics.
AB  - Non-dipper blood pressure (NDP) as an indicator of autonomic dysfunction could be
      associated with hypertensive response to exercise (HRE) in diabetic patients. HRE
      was determined as a predictor of development of unborn hypertension. We aimed to
      investigate if any correlation among NDP and HRE in normotensive type 2 diabetic
      patients. A total of 59 consecutive type 2 diabetic patients without history of
      hypertension and with normal blood pressure (BP) on ambulatory blood pressure
      monitoring (ABPM) were enrolled to the study. We divided the study population in
      to two groups depending on their BP on ABPM as dipper (group 1) or non-dipper
      (group 2). There were 22 patients (mean age 49.5 +/- 7 and 10 male) in group 1
      and 37 patients (mean age 53.1 +/- 10 and 14 male) in group 2. Daytime diastolic
      and mean BP of dippers and night time systolic and mean BP of non-dippers were
      significantly higher. HRE was not significantly different between groups (59% vs.
      62%, p = 0.820). Hemodynamic parameters during the exercise test were similar. At
      multivariate linear regression analysis, resting office systolic blood pressure
      (SBP) (r = 0.611, p < 0.001), male sex (r = 0.266, p = 0.002) and age (r = 0.321,
      p = 0.010) were independently correlated with peak exercises SBP. Logistic
      regression analyses identified the resting office SBP (OR 1.191, 95% CI 1.080
      1.313; p < 0.001) and age (OR 1.161, 95% CI 1.038-1.298; p = 0.012) were
      independent predictors of HRE. This study revealed that HRE is not related with
      non-dipper BP in diabetic patients. This study could inspire to further studies
      to explore the main reasons of HRE in diabetes mellitus.

PMID- 24878251
TI  - Effects of different sonic activation protocols on debridement efficacy in teeth
      with single-rooted canals.
AB  - OBJECTIVES: The effects of different EndoActivator(r) (EA) sonic activation
      protocols on root canal debridement efficacy were examined. METHODS: Root canals
      in 48 single-rooted teeth were instrumented, irrigated initially with NaOCl and
      divided into 6 groups (N=8) based on the application time of QMix (antimicrobial
      calcium-chelating irrigant), and the time and sequence of EA irrigant activation 
      Positive Control: 90s QMix; Negative Control: 90s saline; Group 1A: 15s QMix+15s
      QMix with EA-activation; Group 1B: 30s QMix+30s of QMix with EA-activation; Group
      2A: 15s QMix with EA-activation+15s QMix; Group 2B: 30s QMix with EA
      activation+30s QMix. Split roots were examined with scanning electron microscopy
      for assignment of smear and debris scores in locations along the coronal, middle
      and apical thirds of the canals. The overall cleanliness of pooled canal
      locations in the Positive Control and the 4 experimental groups were compared
      with chi-square tests. RESULTS: Significant differences were detected among the 5
      groups (P<0.001). Post hoc pairwise comparisons indicated that the overall canal
      cleanliness was in the order (from best to worst): 1B=2B>2A>1A>Positive Control.
      Completely clean canals could not be achieved due to the absence of continuous
      irrigant flow for EA to clear intraradicular debris. CONCLUSIONS: Irrespective of
      the sonic activation sequence, irrigant activation for 30s during a 60-s period
      of QMix application appears to maximise the smear layer and debris removal
      potential of the EndoActivator(r) system. CLINICAL SIGNIFICANCE: Sonic activation
      of root canal irrigants produces cleaner root canals and reduces the time
      required for final delivery of a canal wall smear later-removing irrigant when
      compared to the use of needle irrigation alone.

PMID- 24878254
TI  - Penetration of moxifloxacin through crosslinked corneas.
AB  - PURPOSE: To determine the ability of moxifloxacin to penetrate the rabbit eye
      after corneal collagen crosslinking (CXL) with riboflavin and ultraviolet-A light
      irradiation. SETTING: Harlan Biotech Israel, Rehovot, Israel. DESIGN:
      Experimental study. METHODS: One eye of 10 New Zealand white rabbits had CXL
      treatment. One month after treatment and 1 hour before an aqueous humor sample
      was obtained, 1 drop of 5 mg/mL moxifloxacin (Vigamox) was applied to both eyes
      of each rabbit every 15 minutes for a total of 4 drops. The aqueous humor samples
      were sent for high-performance liquid chromatography for antibiotic-concentration
      analysis. The eyes were enucleated and sent for histology analysis. RESULTS:
      Moxifloxacin levels were obtained and analyzed for all 20 eyes. The mean level of
      moxifloxacin was 2.26 MUg/mL +/- 0.89 (SD) (range 1.09 to 4.20 MUg/mL) in the
      treated eyes and 2.43 +/- 1.17 MUg/mL (range 0.89 to 4.72 MUg/mL) in the
      untreated eyes. The difference between the groups was not statistically
      significant. Of the 10 eye pairs, lower moxifloxacin aqueous humor concentrations
      were found in 6 treated eyes and 4 untreated eyes. CONCLUSION: Penetration of
      moxifloxacin into the anterior chamber of rabbits was not influenced by previous
      CXL treatment. FINANCIAL DISCLOSURES: No author has a financial or proprietary
      interest in any material or method mentioned.

PMID- 24878255
TI  - Effects of amphetamine, diazepam and caffeine on polysomnography (EEG, EMG, EOG)
      derived variables measured using telemetry in Cynomolgus monkeys.
AB  - INTRODUCTION: Medication-induced sleep disturbances are a major concern in drug
      development as a multitude of prescription drugs alter sleep patterns, often
      negatively. Polysomnography is used in clinical diagnostics but is also
      applicable to animal models. Rodent sleep architecture (nocturnal) differs from
      larger diurnal mammals, including humans, increasing the translational potential
      of non-rodent species to the clinic. This study aimed to characterize the
      response to pharmacological agents known to affect sleep structure and EEG
      activity in a non-human primate (Macaca fascicularis) using telemetry-based
      polysomnography. METHODS: Animals were instrumented with telemetry transmitters
      for continuous electroencephalogram (EEG), electro-oculogram (EOG) and
      electromyogram (EMG) monitoring combined with video. EEG, EMG and EOG were
      monitored for 12 to 24h to establish baseline values, followed by administration
      of pharmacological agents (saline, d-amphetamine, diazepam or caffeine). RESULTS:
      Amphetamine (0.3 and 1mg/kg, by oral administration (PO)) significantly reduced
      total sleep time, including the duration of both non-rapid eye movement [NREM]
      sleep and REM sleep. It also decreased EEG activity in low frequencies (i.e., 4
      6Hz) during wakefulness. Diazepam (2mg/kg, PO) did not significantly alter sleep
      duration, but importantly reduced EEG activity in low frequencies (approximately
      2-12Hz) during wakefulness, NREM and REM sleep. Finally, caffeine (10 and
      30mg/kg, PO) decreased both NREM and REM sleep duration. In addition, spectral
      analysis revealed important decreases in low frequency activity (i.e., 1-8Hz)
      during wakefulness with a parallel increase in high frequency activity (i.e., 20
      50Hz) during NREM sleep. DISCUSSION: As these observations are similar to
      previously reported pharmacological effects in humans, results support that EEG,
      EOG and EMG monitoring by telemetry in Cynomolgus monkeys represents a useful non
      clinical model to investigate and quantify drug-induced sleep disturbances.

PMID- 24878256
TI  - Interactions of gold nanoparticles with a phospholipid monolayer membrane on
      mercury.
AB  - It is demonstrated that a compact monolayer of 1,2-dioleoyl-sn-glycero-3
      phosphocholine adsorbed to a hanging mercury drop electrode can serve as a simple
      electrochemical model system to study biomembrane penetration by gold
      nanoparticles. The hydrogen redox-chemistry characteristic of ligand-stabilized
      gold nanoparticles in molecularly close contact with a mercury electrode is used
      as an indicator of membrane penetration. Results for water-dispersible gold
      nanoparticles of two different sizes are reported, and comparisons are made with
      the cellular uptake of the same preparations of nanoparticles by a common human
      fibroblast cell line. The experimental system described here can be used to study
      physicochemical aspects of membrane penetration in the absence of complex
      biological mechanisms, and it could also be a starting point for the development
      of a test bed for the toxicity of nanomaterials. 

PMID- 24878257
TI  - Water interactions with acetic acid layers on ice and graphite.
AB  - Adsorbed organic compounds modify the properties of environmental interfaces with
      potential implications for many Earth system processes. Here, we describe
      experimental studies of water interactions with acetic acid (AcOH) layers on ice
      and graphite surfaces at temperatures from 186 to 200 K. Hyperthermal D2O water
      molecules are efficiently trapped on all of the investigated surfaces, with only
      a minor fraction that scatters inelastically after an 80% loss of kinetic energy
      to surface modes. Trapped molecules desorb rapidly from both MUm-thick solid AcOH
      and AcOH monolayers on graphite, indicating that water has limited opportunities
      to form hydrogen bonds with these surfaces. In contrast, trapped water molecules
      bind efficiently to AcOH-covered ice and remain on the surface on the
      observational time scale of the experiments (60 ms). Thus, adsorbed AcOH is
      observed to have a significant impact on water-ice surface properties and to
      enhance the water accommodation coefficient compared to bare ice surfaces. The
      mechanism for increased water uptake and the implications for atmospheric cloud
      processes are discussed. 

PMID- 24878258
TI  - [Prevalence of the use of hypnotics and sedatives among the working population
      and associated work-related stress factors].
AB  - OBJECTIVE: To explore the prevalence of the use of hypnotics and sedatives in a
      sample of the Spanish working population and to examine its association with
      certain work-related stress factors. METHODS: Using data from the 2007 Spanish
      Household Survey on Alcohol and Drugs (Encuesta Domiciliaria sobre Alcohol y
      Drogas en Espana [EDADES]), we analyzed the distribution of the use of hypnotics
      and sedatives in the previous month in the working population aged 16 to 64 years
      old (n=13,005). Associations with exposure to certain work-related stress factors
      (noxious working environment, precariousness, workload, and social support) were
      examined using logistic regression modelling. RESULTS: The prevalence of the use
      of hypnotics and sedatives among women in the previous month doubled that of men
      (6.5% and 3.3%, respectively), while use among the oldest age group was twice
      that of the youngest group in both sexes (10.2% in women and 5.5% in men older
      than 45 years), and was four times higher among those reporting poor health
      (18.9% in women and 11% in men). Concerning work-related stress, exposure to
      moderate (OR: 1.96; 95%CI: 1.31-2.92) and high (OR: 1.95; 95%CI: 1.14-3.34)
      levels of precariousness in men and moderate levels in women (OR: 1.43; 95%CI:
      1.03-1.99) was associated with the use of hypnotics and sedatives. CONCLUSIONS:
      The prevalence of the use of hypnotics and sedatives was high in women and in
      workers older than 45 years. Further research is needed on the relationship
      between the use of hypnotics and sedatives and workers' health, and on the role
      that work-related stress factors play in this association.

PMID- 24878259
TI  - [Notes on vital statistics for the study of perinatal health].
AB  - Vital statistics, published by the National Statistics Institute in Spain, are a
      highly important source for the study of perinatal health nationwide. However,
      the process of data collection is not well-known and has implications both for
      the quality and interpretation of the epidemiological results derived from this
      source. The aim of this study was to present how the information is collected and
      some of the associated problems. This study is the result of an analysis of the
      methodological notes from the National Statistics Institute and first-hand
      information obtained from hospitals, the Central Civil Registry of Madrid, and
      the Madrid Institute for Statistics. Greater integration between these
      institutions is required to improve the quality of birth and stillbirth
      statistics. 

PMID- 24878260
TI  - Unraveling the novel function of the DNA repair enzyme 8-oxoguanine-DNA
      glycosylase in activating key signaling pathways.

PMID- 24878262
TI  - What impact did a Paediatric Early Warning system have on emergency admissions to
      the paediatric intensive care unit? An observational cohort study.
AB  - The ideology underpinning Paediatric Early Warning systems (PEWs) is that earlier
      recognition of deteriorating in-patients would improve clinical outcomes.
      OBJECTIVE: To explore how the introduction of PEWs at a tertiary children's
      hospital affects emergency admissions to the Paediatric Intensive Care Unit
      (PICU) and the impact on service delivery. To compare 'in-house' emergency
      admissions to PICU with 'external' admissions transferred from District General
      Hospitals (without PEWs). METHOD: A before-and-after observational study August
      2005-July 2006 (pre), August 2006-July 2007 (post) implementation of PEWs at the
      tertiary children's hospital. RESULTS: The median Paediatric Index of Mortality
      (PIM2) reduced; 0.44 vs 0.60 (p<0.001). Fewer admissions required invasive
      ventilation 62.7% vs 75.2% (p=0.015) for a shorter median duration; four to two
      days. The median length of PICU stay reduced; five to three days (p=0.002). There
      was a non-significant reduction in mortality (p=0.47). There was no comparable
      improvement in outcome seen in external emergency admissions to PICU. A 39%
      reduction in emergency admission total beds days reduced cancellation of major
      elective surgical cases and refusal of external PICU referrals. CONCLUSIONS:
      Following introduction of PEWs at a tertiary children's hospital PIM2 was
      reduced, patients required less PICU interventions and had a shorter length of
      stay. PICU service delivery improved.

PMID- 24878263
TI  - Canine stage 1 periodontal disease: a latent pathology.
AB  - To evaluate the potential health issues associated with periodontal disease (PD)
      in dogs, 1004 teeth from 25 dogs were examined. The dogs were randomly selected,
      aged 2-14 years, and had at least 95% of their teeth at the first PD stage.
      Significant positive correlations between plaque grade (PG) and gum inflammation,
      gingival regression, periodontal pocket, age and serum alanine aminotransferase
      (ALT) activity were identified. In contrast, PG was negatively correlated to
      total platelet count. Altogether, these findings suggest that prevention and
      therapy at the first PD stages can have an important impact on the general health
      condition of dogs.

PMID- 24878264
TI  - The prevalence of lameness on New Zealand dairy farms: a comparison of farmer
      estimate and locomotion scoring.
AB  - Lameness is a significant welfare and economic issue in all dairy systems.
      However, there is only a limited amount of published data on the incidence and
      prevalence of lameness in the pasture-based systems used in New Zealand. One key
      area where knowledge is lacking is how well farmer perception of lameness matches
      that identified by more objective locomotion scoring. Previous studies of this
      topic have focussed on housed cows. Fifty-nine herds, 26 based in the South
      Island and 33 in the North Island, were surveyed. All farms were visited on one
      occasion at the expected peak time for lameness, and data were collected via a
      questionnaire which included details on farm size, and productivity as well as
      lameness. The latter included a farmer estimate of the number of lame cows which
      were currently on-farm and the number of lame cows there had been in the previous
      12 months. Whole herd locomotion scoring, using the DairyCo 0-3 scale, was then
      used to estimate the prevalence of lameness in the herd. Farmers estimated that
      between 0 and 20% of their herd was lame (mean 2.2%), while locomotion scoring
      identified that between 1.2% and 36% of a herd was lame (mobility score >= 2;
      mean 8.1%). This finding indicated that, on a herd basis, only 27.3% (range 0
      95%) of the cows with reduced mobility had been identified as such. There was no
      significant effect of herd size or geographical location on this percentage. The
      prevalence of lameness in this study was much lower than that reported in housed
      cattle, but the percentage of cows with reduced mobility recognised as lame was
      very similar. There is significant room for improvement in the detection of
      lameness on New Zealand farms, where routine mobility scoring, particularly at
      critical periods, could prove a valuable tool.

PMID- 24878265
TI  - What progress has been made in the understanding and treatment of degenerative
      lumbosacral stenosis in dogs during the past 30 years?
AB  - An association between degenerative changes in the lumbosacral region of the
      vertebral column and clinical signs of pain and pelvic limb dysfunction has long
      been recognized in dogs and has become known as degenerative lumbosacral stenosis
      syndrome. Over the past two decades, methods of imaging this condition have
      advanced greatly, but definitive criteria for a reliable diagnosis using physical
      examination, imaging and electrodiagnostics remain elusive. Available treatment
      options have changed little over more than 30 years but, more importantly, there
      is a lack of comparative studies and little progress has been made in providing
      evidence-based recommendations for the treatment of affected dogs. This review
      provides an overview of the changes in diagnosis, understanding and treatment of
      lumbosacral disease in dogs over the past 30 years. Approaches to address the
      unanswered questions regarding treatment choice are also proposed. 

PMID- 24878266
TI  - The influence of sex hormones on seizures in dogs and humans.
AB  - Epilepsy is the most common chronic neurological disorder in both humans and
      dogs. The effect of sex hormones on seizures is well documented in human
      medicine. Catamenial epilepsy is defined as an increase in frequency and severity
      of seizures during certain periods of the menstrual cycle. Oestradiol increases
      seizure activity and progesterone is believed to exhibit a protective effect. The
      role of androgens is controversial and there is a lack of research focusing on
      androgens and epilepsy. Indeed, little is known about the influence of sex
      hormones on epilepsy in dogs. Sterilisation is believed to improve seizure
      control, but no systematic research has been conducted in this field. This review
      provides an overview of the current literature on the influence of sex hormones
      on seizures in humans. The literature on idiopathic epilepsy in dogs was assessed
      to identify potential risk factors related to sex and sterilisation status. In
      general, there appears to be an over-representation of male dogs with idiopathic
      epilepsy but no explanation for this difference in prevalence between sexes has
      been reported. In addition, no reliable conclusions can be drawn on the effect of
      sterilisation due to the lack of focused research and robust scientific evidence.

PMID- 24878268
TI  - Prehospital oxygen administration for chest pain patients decreases significantly
      following implementation of the 2010 AHA guidelines.
AB  - OBJECTIVES: The purpose of this study was to examine trends in oxygen
      administration following the 2010 American Heart Association guidelines
      recommendation to withhold oxygen therapy for patients with uncomplicated
      presentations of ACS whose SpO2 is 94% or higher. METHODS: Following IRB review
      and approval, we performed a retrospective analysis of data obtained from
      Fisdap(TM), a national, clinical skills tracking system for paramedic students
      between June 2010 and December 2012. Inclusion criteria included: 1) student
      consent for research, 2) cardiac chest pain recorded as the chief complaint, and
      3) SpO2 data available for review. O2 administration, route, and dose were
      abstracted, and the percent of patient encounters with oxygen administration was
      calculated for each year. Unadjusted logistic regression was used to determine if
      O2 administration rates changed significantly over the study period. Unadjusted
      logistic regression was also used to determine if there was a difference in the
      odds of receiving oxygen based on a patient's SpO2 value. RESULTS: 10,552 patient
      encounters by 2,447 paramedic students from 195 paramedic programs representing
      49 states were included for analysis. Prior to release of the new guidelines
      (2010), 71.9% (95% CI 69.8-74.0%) of patients with SpO2 >= 94% received
      supplemental O2. Rates of O2 administration were significantly lower in 2011
      (64%; 95% CI 62.7-65.3%) and in 2012 (53.1%; 95% CI 51.5-54.7). The odds of a
      hemodynamically stable chest pain patient with SpO2 >= 94% receiving supplemental
      oxygen in 2011 were 1.4 times lower compared to patients in 2010 (95% CI 1.3
      1.6). Similarly, the odds of patients in 2012 receiving supplemental oxygen were
      2.3 times lower compared to patients in 2010 (95% CI 2.0-2.6). The odds of
      receiving supplemental oxygen decreased by 4% for each 1% increase in SpO2 beyond
      the 94% threshold (OR = 0.96; 95% CI 0.94-0.98). CONCLUSIONS: The prehospital
      administration of supplemental O2 decreased significantly following release of
      the 2010 updated guidelines; however, our data revealed that 50% of patients not
      meeting criteria for administration still received supplemental O2.

PMID- 24878269
TI  - Novel aza-analogous ergoline derived scaffolds as potent serotonin 5-HT6 and
      dopamine D2 receptor ligands.
AB  - By introducing distal substituents on a tetracyclic scaffold resembling the
      ergoline structure, two series of analogues were achieved exhibiting subnanomolar
      receptor binding affinities for the dopamine D2 and serotonin 5-HT6 receptor
      subtype, respectively. While the 5-HT6 ligands were antagonists, the D2 ligands
      displayed intrinsic activities ranging from full agonism to partial agonism with
      low intrinsic activity. These structures could potentially be interesting for
      treatment of neurological diseases such as schizophrenia, Parkinson's disease,
      and cognitive deficits. 

PMID- 24878267
TI  - Evaluation of prognostic indicators using validated canine insulinoma tissue
      microarrays.
AB  - Tissue microarray (TMA) technology allows analysis of multiple tumour samples
      simultaneously on a single slide. The aim of the present study was to develop and
      assess a TMA containing 32 primary canine insulinomas and 13 insulinoma
      metastases. The results of histopathological and immunohistochemical analyses of
      triplicate core biopsies were compared with those of individual tissue sections
      using weighted kappa statistics. Inter-observer agreement of TMA
      immunohistochemistry scores were assessed for chromogranin A (CgA), insulin,
      growth hormone (GH), growth hormone receptor (GHR) and Ki67 index, as well as the
      prognostic utility of clinicopathological, histopathological and
      immunohistochemical criteria. There was substantial agreement of scores for
      histopathological parameters (kappa = 0.64-0.70) and a substantial to near
      perfect agreement for homogenous immunohistochemical parameters (kappa = 0.69
      1.00). Except for GH, which demonstrated heterogeneous staining, there was good
      to excellent inter-observer agreement for all other immunohistochemical staining
      scores (intra-class correlation coefficients: 0.70-1.00). On univariate analysis,
      the presence of nuclear atypia was significantly predictive of disease-free
      intervals (DFIs) for canine insulinoma, while tumour size, TNM stage, necrosis
      and Ki67 index were significant in terms of prognosis, with respect to both DFI
      and survival time. On multivariate analysis, tumour size and Ki67 index retained
      predictive power for survival time, as did tumour size for DFI. This study
      confirms the applicability of TMA technology for evaluation of canine insulinoma.

PMID- 24878270
TI  - Clinical outcome of microscopic lumbar spinous process-splitting laminectomy:
      clinical article.
AB  - OBJECT: The authors sought to quantify the clinical outcome of microscopic lumbar
      spinous process-splitting laminectomy in patients with lumbar spinal stenosis
      (LSS). They performed a microscopic laminectomy in which the spinous process is
      split longitudinally into 2 halves. For single-level decompression, they inserted
      a tubular retractor between the split process. METHODS: Data obtained in a total
      of 124 patients were retrospectively analyzed. Patients were divided into 2
      groups: the "slip" group, comprising patients with spondylolisthesis-type LSS
      with vertebral body slippage (Group 1), and the "nonslip" group, comprising
      patients with spondylosis-type LSS without vertebral body slippage or with LSS
      due to central protrusion of lumbar disc herniation. Clinical outcome in all
      patients was evaluated by using the Japanese Orthopaedic Association score. In
      the slip group, slippage and instability rates were evaluated by using pre- and
      postoperative dynamic radiographs in the sagittal plane. Postoperative CT images
      were used to evaluate bony union at 2 sites: a region between the left and right
      portions of the halved spinous process and a region between the base of the
      halved process and vertebral arch. Signal intensity of the multifidus muscle at
      individual decompression levels was evaluated on pre- and postoperative T1- and
      T2-weighted MR images. RESULTS: Preoperative clinical symptoms improved
      significantly after surgery in all patients. Slippage and instability rates in
      the slip group showed no significant differences when pre- and postoperative
      conditions were compared. Union rates at the region between the left and right
      portions of the halved process and the region between the base of the halved
      process and vertebral arch were 97.1% and 82.5%, respectively. Magnetic resonance
      imaging showed only a small amount of fat infiltration in the multifidus muscle
      after surgery in 12.2% of cases. CONCLUSIONS: The authors recommend microscopic
      lumbar spinous process-splitting laminectomy as a promising minimally invasive
      surgery for the treatment of LSS.

PMID- 24878272
TI  - Ganglioneuroblastoma of filum terminale: case report.
AB  - OBJECT: Neuroblastic tumors can be classified as neuroblastoma,
      ganglioneuroblastoma (GNB), or ganglioneuroma. Ganglioneuroblastomas consist of
      small, round, immature neuroblast cells and matured ganglion cells. They are most
      commonly found in the mediastinum and retroperitoneum; intraspinal GNBs are
      extremely rare. There are only 5 cases of intraspinal GNB reported in the English
      literature. The authors report a case of GNB of the filum terminale. The duration
      of follow-up after the initial treatment is longer than in any other published
      reports. METHODS: A 36-year-old woman underwent resection of an intradural
      extramedullary tumor at L1-2 in 1993. Pathological diagnosis was GNB. After
      surgery, her symptoms resolved and she recovered to a normal condition. In 2009,
      when she was 53 years old, she presented to the hospital with paralysis of both
      legs. Magnetic resonance imaging suggested recurrence of spinal tumor. She
      underwent subtotal resection of the tumors, followed by 4 weeks of radiation
      therapy. RESULTS: Neurological symptoms improved, and, after radiation therapy,
      the patient was able to walk with a crutch. Histological investigation of the
      excised tumor indicated that it was a nodular type GNB, which was consistent with
      the diagnosis from the time of the initial surgery in 1993. Follow-up MRI studies
      showed no growth of residual tumors in the 3 years following the surgery.
      CONCLUSIONS: The authors present a rare case of spinal GNB. The duration of
      follow-up after the initial surgery in 1993 represents the longest description of
      clinical course after treatment for spinal GNB.

PMID- 24878271
TI  - Paraspinal muscle morphometry in cervical spondylotic myelopathy and its
      implications in clinicoradiological outcomes following central corpectomy:
      clinical article.
AB  - OBJECT: The objective of this study was to assess the cross-sectional areas
      (CSAs) of the superficial, deep flexor (DF), and deep extensor (DE) paraspinal
      muscles in patients with cervical spondylotic myelopathy (CSM), and to evaluate
      their correlations with functional status and sagittal spinal alignment changes
      following central corpectomy with fusion and plating. METHODS: In this
      retrospective study of 67 patients who underwent central corpectomy with fusion
      and plating for CSM, the CSAs of the paraspinal muscles were calculated on the
      preoperative T2-weighted axial MR images and computed as ratios with respect to
      the corresponding vertebral body areas (VBAs) and as flexor/extensor CSA ratios.
      These ratios were then compared with those in the normative population and
      analyzed with respect to various clinicoradiological factors, including pain
      status, Nurick grade, and segmental angle change at follow-up (SACF). RESULTS:
      The mean CSA values for all muscle groups and the DF/DE ratio were significantly
      lower in the study cohort compared with an age- and sex-matched normative study
      group (p < 0.001). Among various independent variables tested in a multivariate
      regression analysis, increasing age and female sex significantly predicted a
      lower total extensor CSA/VBA ratio (p < 0.001), while a longer duration of
      symptoms significantly predicted a greater total flexor/total extensor CSA ratio
      (p = 0.02). In patients undergoing single-level corpectomy, graft subsidence had
      a positive correlation with SACF in all patients (p < 0.05), irrespective of the
      preoperative segmental angle and curvature, while in patients undergoing 2-level
      corpectomy, graft subsidence demonstrated such a correlation only in the subgroup
      with lordotic curvatures (p = 0.02). Among the muscle area ratios, the DF/DE
      ratio demonstrated a negative correlation with SACF in the subgroup with
      preoperative straight or kyphotic segmental angles (p = 0.04 in the single
      corpectomy group, p = 0.01 in the 2-level corpectomy group). There was no
      correlation of any of the muscle ratios with change in Nurick grade. CONCLUSIONS:
      Patients with CSM demonstrate significant atrophy in all the flexor and extensor
      paraspinal muscles, and also suffer a reduction in the protective effect of a
      strong DF/DE CSA ratio. Worsening of this ratio significantly correlates with
      greater segmental kyphotic change in some patients. A physiological mechanism
      based on DF dysfunction is discussed to elucidate these findings that have
      implications in preventive physiotherapy and rehabilitation of patients with CSM.
      Considering that the influence of a muscle ratio was significant only in patients
      with hypolordosis, a subgroup that is known to have facetal ligament laxity, it
      may also be postulated that ligamentous support supersedes the influence of
      paraspinal muscles on postoperative sagittal alignment in CSM.

PMID- 24878273
TI  - Outcomes after decompressive laminectomy for lumbar spinal stenosis: comparison
      between minimally invasive unilateral laminectomy for bilateral decompression and
      open laminectomy: clinical article.
AB  - OBJECT: The development of minimally invasive surgical techniques is driven by
      the quest for better patient outcomes. There is some evidence for the use of
      minimally invasive surgery for degenerative lumbar spine stenosis (LSS), but
      there are currently no studies comparing outcomes with matched controls. The
      object of this study was to compare outcomes following minimally invasive
      unilateral laminectomy for bilateral decompression (ULBD) to a standard "open"
      laminectomy for LSS. METHODS: The authors conducted a prospective, 1:1 randomized
      trial comparing ULBD to open laminectomy for degenerative LSS. The study enrolled
      79 patients between 2007 and 2009, and adequate data for analysis were available
      in 54 patients (27 in each arm of the study). Patient demographic characteristics
      and clinical characteristics were recorded and clinical outcomes were obtained
      using pre- and postoperative Oswestry Disability Index (ODI) scores, visual
      analog scale (VAS) scores for leg pain, patient satisfaction index scores, and
      postoperative 12-Item Short Form Health Survey (SF-12) scores. RESULTS:
      Significant improvements were observed in ODI and VAS scores for both open and
      ULBD interventions (p < 0.001 for both groups using either score). In addition,
      the ULBD-treated patients had a significantly better mean improvement in the VAS
      scores (p = 0.013) but not the ODI scores (p = 0.055) compared with patients in
      the open-surgery group. ULBD-treated patients had a significantly shorter length
      of postoperative hospital stay (55.1 vs. 100.8 hours, p = 0.0041) and time to
      mobilization (15.6 vs. 33.3 hours, p < 0.001) and were more likely to not use
      opioids for postoperative pain (51.9% vs. 15.4%, p = 0.046). CONCLUSIONS: Based
      on short-term follow-up, microscopic ULBD is as effective as open decompression
      in improving function (ODI score), with the additional benefits of a
      significantly greater decrease in pain (VAS score), postoperative recovery time,
      time to mobilization, and opioid use.

PMID- 24878274
TI  - Infrared signature of the early stage microsolvation in the NaSO4-(H2O)1-5
      clusters: a simulation study.
AB  - Infrared photon dissociation (IRPD) spectra of the NaSO4(-)(H2O)n clusters with
      up to five water molecules have been studied using quantum chemical calculations.
      Our calculation reveals that the splitting of the peaks in the ~800-1300 cm(-1)
      region of the IRPD spectra, which contains the information on S-O bond stretching
      of the anion, indicates the deviation of the cation from the C(3v) axis as well
      as the asymmetric distribution of the water molecules. The frequency of the H
      bonded O-H stretching peak in the ~2300-3000 cm(-1) window, on the other hand,
      provides information on the position of the newly added water molecule with
      respect to the cation. The IRPD technique thus provides abundant structural
      information on the early stage of the microsolvation and has the potential to
      become a powerful tool complementary to photoelectron spectroscopy.

PMID- 24878261
TI  - Regulation of obesity and insulin resistance by nitric oxide.
AB  - Obesity is a risk factor for developing type 2 diabetes and cardiovascular
      disease and has quickly become a worldwide pandemic with few tangible and safe
      treatment options. Although it is generally accepted that the primary cause of
      obesity is energy imbalance, i.e., the calories consumed are greater than are
      utilized, understanding how caloric balance is regulated has proven a challenge.
      Many "distal" causes of obesity, such as the structural environment, occupation,
      and social influences, are exceedingly difficult to change or manipulate. Hence,
      molecular processes and pathways more proximal to the origins of obesity-those
      that directly regulate energy metabolism or caloric intake-seem to be more
      feasible targets for therapy. In particular, nitric oxide (NO) is emerging as a
      central regulator of energy metabolism and body composition. NO bioavailability
      is decreased in animal models of diet-induced obesity and in obese and insulin
      resistant patients, and increasing NO output has remarkable effects on obesity
      and insulin resistance. This review discusses the role of NO in regulating
      adiposity and insulin sensitivity and places its modes of action into context
      with the known causes and consequences of metabolic disease. 

PMID- 24878275
TI  - Is a search template an ordinary working memory? Comparing electrophysiological
      markers of working memory maintenance for visual search and recognition.
AB  - Visual search requires the maintenance of a search template in visual working
      memory in order to guide attention towards the target. This raises the question
      whether a search template is essentially the same as a visual working memory
      representation used in tasks that do not require attentional guidance, or whether
      it is a qualitatively different representation. Two experiments tested this by
      comparing electrophysiological markers of visual working memory maintenance
      between simple recognition and search tasks. For both experiments, responses were
      less rapid and less accurate in search task than in simple recognition.
      Nevertheless, the contralateral delay activity (CDA), an index of quantity and
      quality of visual working memory representations, was equal across tasks. On the
      other hand, the late positive complex (LPC), which is sensitive to the effort
      invested in visual working memory maintenance, was greater for the search task
      than the recognition task. Additionally, when the same target cue was repeated
      across trials (Experiment 2), the amplitude of visual working memory markers
      (both CDA and LPC) decreased, demonstrating learning of the target at an equal
      rate for both tasks. Our results suggest that a search template is qualitatively
      the same as a representation used for simple recognition, but greater effort is
      invested in its maintenance. 

PMID- 24878276
TI  - Early changes of left ventricular function in young adults with never-treated
      hypertension and no left ventricular hypertrophy: relationships to ambulatory
      blood pressure monitoring.
AB  - The number of young adults with hypertension (HT) is increasing. We investigated
      the changes of left ventricular (LV) function and their relationship to the
      ambulatory blood pressure monitoring (ABPM) parameters in young adults with never
      treated HT and no LV hypertrophy. Consecutive young patients (29.5 +/- 5.9 years)
      with first diagnosed primary HT and sex- and age-matched normotensive controls
      were enrolled. We excluded patients who had LV hypertrophy. ABPM was performed in
      all HT patients. LV strain values were obtained by two-dimensional speckle
      tracking imaging. There was no difference in LV ejection fraction and mass index
      between HT patients (n = 40) and controls (n = 40). LV global longitudinal strain
      (GLS) was lower (p = 0.001) and twist was higher (p = 0.002) in HT patients than
      in controls. LV GLS was significantly correlated to averaged and daytime
      diastolic BP and its variability and most related to daytime diastolic BP (beta =
      0.33, p = 0.03). Patients with high daytime diastolic BP and its variability
      showed lower GLS (both p = 0.02) and higher twist (both p = 0.04) than patients
      with low daytime diastolic BP. Early changes of LV function with decreased GLS
      and increased twist were shown in young HT patients even with no LV hypertrophy
      and daytime diastolic BP and its variability were related to the impairment of LV
      function.

PMID- 24878278
TI  - Structural characterization of a beta-hydroxyacid dehydrogenase from Geobacter
      sulfurreducens and Geobacter metallireducens with succinic semialdehyde reductase
      activity.
AB  - Beta-hydroxyacid dehydrogenase (beta-HAD) genes have been identified in all
      sequenced genomes of eukaryotes and prokaryotes. Their gene products catalyze the
      NAD(+)- or NADP(+)-dependent oxidation of various beta-hydroxy acid substrates
      into their corresponding semialdehyde. In many fungal and bacterial genomes,
      multiple beta-HAD genes are observed leading to the hypothesis that these gene
      products may have unique, uncharacterized metabolic roles specific to their
      species. The genomes of Geobacter sulfurreducens and Geobacter metallireducens
      each contain two potential beta-HAD genes. The protein sequences of one pair of
      these genes, Gs-betaHAD (Q74DE4) and Gm-betaHAD (Q39R98), have 65% sequence
      identity and 77% sequence similarity with each other. Both proteins are observed
      to reduce succinic semialdehyde, a 4-carbon substrate instead of the typical beta
      HAD 3-carbon substrate, to gamma-hydroxybutyric acid. To further explore the
      structural and functional characteristics of these two beta-HADs with a less
      frequently observed substrate specificity, crystal structures for Gs-betaHAD and
      Gm-betaHAD in complex with NADP(+) were determined to a resolution of 1.89 A and
      2.07 A, respectively. The structures of both proteins are similar, composed of 14
      alpha-helices and nine beta-strands organized into two domains. Domain 1 (1-165)
      adopts a typical Rossmann fold composed of two alpha/beta units: a six-strand
      parallel beta-sheet surrounded by six alpha-helices (alpha1-alpha6) followed by a
      mixed three-strand beta-sheet surrounded by two alpha-helices (alpha7 and
      alpha8). Domain 2 (166-287) is composed of a bundle of seven alpha-helices
      (alpha9-alpha14). Four functional regions conserved in all beta-HADs are
      spatially located near each other, with a buried molecule of NADP(+), at the
      interdomain cleft. Comparison of these Geobacter structures to a closely related
      beta-HAD from Arabidopsis thaliana in the apo-NADP(+) and apo-substrate bound
      state suggests that NADP(+) binding effects a rigid body rotation between Domains
      1 and 2. Bound near the Substrate-Binding and Catalysis Regions in two of the
      eight protomers in the asymmetric unit of Gm-betaHAD is a glycerol molecule that
      may mimic features of bound biological substrates. 

PMID- 24878280
TI  - "There were giants in the earth in those days." Genesis 6:4.

PMID- 24878281
TI  - Francois Jacob's spirit.

PMID- 24878279
TI  - Divergent effect of glycosaminoglycans on the in vitro aggregation of serum
      amyloid A.
AB  - Serum amyloid A (SAA) is an apolipoprotein involved in poorly understood roles in
      inflammation. Upon trauma, hepatic expression of SAA rises 1000 times the basal
      levels. In the case of inflammatory diseases like rheumatoid arthritis, there is
      a risk for deposition of SAA fibrils in various organs leading to Amyloid A (AA)
      amyloidosis. Although the amyloid deposits in AA amyloidosis accumulate with the
      glycosaminoglycan (GAG) heparan sulfate, the role GAGs play in the function and
      pathology of SAA is an enigma. It has been shown that GAG sulfation is a
      contributing factor in protein fibrillation and for co-aggregating with a
      plethora of amyloidogenic proteins. Herein, the effects of heparin, heparan
      sulfate, hyaluronic acid, chondroitin sulfate A, and heparosan on the
      oligomerization and aggregation properties of pathogenic mouse SAA1.1 were
      investigated. Delipidated SAA was used to better understand the interactions
      between SAA and GAGs without the complicating involvement of lipids. The results
      revealed-to varying degrees-that all GAGs accelerated SAA1.1 aggregation, but had
      variable effects on its fibrillation. Heparan sulfate, hyaluronic acid, and
      heparosan did not affect much the fibrillation of SAA1.1. In contrast,
      chondroitin sulfate A blocked SAA fibril formation and facilitated the formation
      of spherical aggregates of various sizes. Interestingly, heparin caused formation
      of spherical SAA1.1 aggregates of various sizes, vast amounts of thin
      protofibrils, and few long fibrils of various heights. These results suggest that
      GAGs may have an intrinsic and divergent influence on the aggregation and
      fibrillation of HDL-free SAA1.1 in vivo, with functional and pathological
      implications. 

PMID- 24878277
TI  - Toward a conceptualization of retrohippocampal contributions to learning and
      memory.
AB  - A wealth of data supports the notion that the hippocampus binds objects and
      events together in place and time. In support of this function, a cortical
      circuit that includes the retrosplenial cortex (RSC) and various structures in
      the parahippocampal region is thought to provide the hippocampus with essential
      information regarding the physical and temporal context in which the object/event
      occurs. However, it remains unclear if and how individual components of this so
      called 'where' circuit make unique contributions to processing context-related
      information. Here we focus on the RSC and the postrhinal cortex (POR; homologous
      with parahippocampal cortex (PHC) in primates), two of the most strongly
      interconnected components of the where pathway and the foci of an increasing
      amount of recent research. Much of the behavioral evidence to date suggests that
      RSC and POR/PHC work closely together as a functional unit. We begin by briefly
      reviewing studies that have investigated the involvement of RSC and POR/PHC in
      contextual and spatial learning, both of which involve learning associations and
      relationships between the individual stimuli that compose an environment (i.e.,
      where information). However, we propose that potential differences have been
      overlooked because most studies to date have relied on behavioral paradigms and
      experimental approaches that are not well suited for distinguishing between
      different aspects of information processing. We then consider the anatomical
      differences between RSC and POR/PHC and emerging behavioral evidence that gives
      rise to a working model of how these regions may differentially contribute to
      hippocampal-dependent learning and memory. We then discuss experimental designs
      and behavioral methods that may be useful in testing the model. Finally,
      approaches are described that may be valuable in probing the nature of
      information processing and neuroplasticity in the myriad of local circuits that
      are nested within the where pathway. 

PMID- 24878282
TI  - Editorial: traumatic brain injury and postoperative CT.

PMID- 24878283
TI  - Magnetic resonance neurography evaluation of chronic extraspinal sciatica after
      remote proximal hamstring injury: a preliminary retrospective analysis.
AB  - OBJECT: Extraspinal sciatica can present unique challenges in clinical diagnosis
      and management. In this study, the authors evaluated qualitative and quantitative
      patterns of sciatica-related pathology at the ischial tuberosity on MR
      neurography (MRN) studies performed for chronic extraspinal sciatica. METHODS:
      Lumbosacral MRN studies obtained in 14 patients at the University of California,
      San Francisco between 2007 and 2011 were retrospectively reviewed. The patients
      had been referred by neurosurgeons or neurologists for chronic unilateral
      sciatica (>= 3 months), and the MRN reports described asymmetrical increased T2
      signal within the sciatic nerve at the level of the ischial tuberosity. MRN
      studies were also performed prospectively in 6 healthy volunteers. Sciatic nerve
      T2 signal intensity (SI) and cross-sectional area at the ischial tuberosity were
      calculated and compared between the 2 sides in all 20 subjects. The same
      measurements were also performed at the sciatic notch as an internal reference.
      Adjacent musculoskeletal pathology was compared between the 2 sides in all
      subjects. RESULTS: Seven of the 9 patients for whom detailed histories were
      available had a specific history of injury or trauma near the proximal hamstring
      preceding the onset of sciatica. Eight of the 14 patients also demonstrated soft
      tissue abnormalities adjacent to the proximal hamstring origin. The remaining 6
      had normal muscles, tendons, and marrow in the region of the ischial tuberosity.
      There was a significant difference in sciatic nerve SI and size between the
      symptomatic and asymptomatic sides at the level of the ischial tuberosity, with a
      mean adjusted SI of 1.38 compared with 1.00 (p < 0.001) and a mean cross
      sectional nerve area of 0.66 versus 0.54 cm(2) (p = 0.002). The control group
      demonstrated symmetrical adjusted SI and sciatic nerve size. CONCLUSIONS: This
      study suggests that chronic sciatic neuropathy can be seen at the ischial
      tuberosity in the setting of prior proximal hamstring tendon injury or adjacent
      soft-tissue abnormalities. Because hamstring tendon injury as a cause of chronic
      sciatica remains a diagnosis of exclusion, this distinct category of patients has
      not been described in the radiographic literature and merits special attention
      from clinicians and radiologists in the management of extraspinal sciatica.
      Magnetic resonance neurography is useful for evaluating chronic sciatic
      neuropathy both qualitatively and quantitatively, particularly in patients for
      whom electromyography and traditional MRI studies are unrevealing.

PMID- 24878284
TI  - Intractable yawning associated with mature teratoma of the supramedial
      cerebellum.
AB  - Yawning occurs in various conditions such as hypoxia, epilepsy, and sleep
      disorders including sleep apnea. Intractable yawning associated with a brain
      tumor has been rarely reported. A 19-year-old woman presented with intractable
      yawning. Magnetic resonance imaging showed a tumor in the supramedial cerebellum
      that compressed the dorsal side of the midbrain and upper pons. After subtotal
      removal of the tumor, the yawning completely disappeared. Postoperative MRI
      showed resolution of compression of the brainstem. The tumor was histologically
      diagnosed as a mature teratoma. The present case suggested that the intractable
      yawning resulted from the tumor compressing the dorsal side of the junction
      between the midbrain and pons. 

PMID- 24878285
TI  - Letter to the editor: delayed ipsilateral hemorrhage following aneurysm treatment
      with flow diverter.

PMID- 24878286
TI  - Volumetric response to radiosurgery for brain metastasis varies by cell of
      origin.
AB  - OBJECT: The aim of this study was to evaluate the imaging response of brain
      metastases after radiosurgery and to correlate the response with tumor type and
      patient survival. METHODS: The authors conducted a retrospective review of
      patients who had undergone Gamma Knife radiosurgery for brain metastases from non
      small cell lung cancer (NSCLC), breast cancer, or melanoma. The imaging
      volumetric response by tumor type was plotted at 3-month intervals and classified
      as a sustained decrease in tumor volume (Type A), a transient decrease followed
      by a delayed increase in tumor volume (Type B), or a sustained increase in tumor
      volume (Type C). These imaging responses were then compared with patient survival
      and tumor type. RESULTS: Two hundred thirty-three patients with metastases from
      NSCLC (96 patients), breast cancer (98 patients), and melanoma (39 patients) were
      eligible for inclusion in this study. The patients with NSCLC were most likely to
      exhibit a Type A response; those with breast cancer, a Type B response; and those
      with melanoma, a Type C response. Among patients with NSCLC, the median overall
      survival was 11.2 months for those with a Type A response (76 patients), 8.6
      months for those with a Type B response (6 patients), and 10.5 months for those
      with a Type C response (14 patients). Among patients with breast cancer, the
      median overall survival was 16.6 months in those with a Type A response (65
      patients), 18.1 months in those with a Type B response (20 patients), and 7.5
      months in those with a Type C response (13 patients). For patients with melanoma,
      the median overall survival was 5.2 months in those with a Type A response (26
      patients) and 6.7 months in those with a Type C response (13 patients). None of
      the patients with melanoma had a Type B response. The imaging response was
      significantly associated with survival only in patients with breast cancer.
      CONCLUSIONS: The various types of imaging responses of metastatic brain tumors
      after stereotactic radiosurgery depend in part on tumor type. However, the type
      of response only correlates with survival in patients with breast cancer.

PMID- 24878287
TI  - STAT-1 expression is regulated by IGFBP-3 in malignant glioma cells and is a
      strong predictor of poor survival in patients with glioblastoma.
AB  - OBJECT: Insulin-like growth factor binding proteins (IGFBPs) have been implicated
      in the pathogenesis of glioma. In a previous study the authors demonstrated that
      IGFBP-3 is a novel glioblastoma biomarker associated with poor survival. Since
      signal transducer and activator of transcription 1 (STAT-1) has been shown to be
      regulated by IGFBP-3 during chondrogenesis and is a prosurvival and
      radioresistant molecule in different tumors, the aim in the present study was to
      explore the functional significance of IGFBP-3 in malignant glioma cells, to
      determine if STAT-1 is indeed regulated by IGFBP-3, and to study the potential of
      STAT-1 as a biomarker in glioblastoma. METHODS: The functional significance of
      IGFBP-3 was investigated using the short hairpin (sh)RNA gene knockdown approach
      on U251MG cells. STAT-1 regulation by IGFBP-3 was tested on U251MG and U87MG
      cells by shRNA gene knockdown and exogenous treatment with recombinant IGFBP-3
      protein. Subsequently, the expression of STAT-1 was analyzed with real-time
      reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry
      (IHC) in glioblastoma and control brain tissues. Survival analyses were done on a
      uniformly treated prospective cohort of adults with newly diagnosed glioblastoma
      (136 patients) using Kaplan-Meier and Cox regression models. RESULTS: IGFBP-3
      knockdown significantly impaired proliferation, motility, migration, and invasive
      capacity of U251MG cells in vitro (p < 0.005). Exogenous overexpression of IGFBP
      3 in U251MG and U87MG cells demonstrated STAT-1 regulation. The mean transcript
      levels (by real-time RT-PCR) and the mean labeling index of STAT-1 (by IHC) were
      significantly higher in glioblastoma than in control brain tissues (p = 0.0239
      and p < 0.001, respectively). Multivariate survival analysis revealed that STAT-1
      protein expression (HR 1.015, p = 0.033, 95% CI 1.001-1.029) along with patient
      age (HR 1.025, p = 0.005, 95% CI 1.008-1.042) were significant predictors of
      shorter survival in patients with glioblastoma. CONCLUSIONS: IGFBP-3 influences
      tumor cell proliferation, migration, and invasion and regulates STAT-1 expression
      in malignant glioma cells. STAT-1 is overexpressed in human glioblastoma tissues
      and emerges as a novel prognostic biomarker.

PMID- 24878288
TI  - Patients' cosmetic satisfaction, pain, and functional outcomes after supraorbital
      craniotomy through an eyebrow incision.
AB  - OBJECT: The supraorbital approach through an eyebrow incision offers the
      opportunity to access a wide variety of lesions of the anterior, middle, and even
      the posterior fossa. The minimally invasive keyhole craniotomy limits brain
      exploration and retraction and offers the potential for improved surgical
      outcomes and reduced approach-related complications. Patient satisfaction,
      however, has not yet been reported in the literature. METHODS: From January 2002
      through December 2011, the lead author (R.R.) used a supraorbital approach
      through an eyebrow incision for 418 patients with cerebral aneurysms, brain
      tumors or cystic lesions, and other miscellaneous pathological conditions. For
      408 of these patients, a detailed retrospective case note review was conducted to
      extract data on surgical outcomes and complications, and 375 patients completed a
      follow-up patient satisfaction questionnaire. RESULTS: During the early
      perioperative period, 8 patients died (overall mortality rate 2.0%). Among
      patients surveyed, the overall level of satisfaction was high. Patients rated
      pain from the scar and headache on a scale from 1 to 5 (1 = no pain, 5 = severe
      pain) as follows: pain was a score of 1 for 289 patients (77.0%), 2 for 46
      (12.3%), 3 for 22 (5.9%), 4 for 12 (3.2%), and 5 for 6 (1.6%). Patients also
      rated cosmetic outcome on a scale from 1 to 5 (1 = very pleasant, 5 = very
      unpleasant) as follows: outcome was a score of 1 for 315 patients (84.0%), 2 for
      33 (8.8%), 3 for 14 (3.7%), 4 for 10 (2.7%), and 5 for 3 (0.8%). Postoperative
      chewing difficulty was reported for 8 patients (8 [2.1%] temporary, 0 permanent);
      palsy of the frontal muscle for 21 patients (5.6%; 13 [3.5%] temporary, 8 [2.1%]
      permanent); frontal hypesthesia for 31 patients (8.3%; 18 [4.8%] temporary, 13
      [3.4%] permanent); and hyposmia for 11 patients (2.9%; 3 [0.8%] temporary, 8
      [2.1%] permanent). CONCLUSIONS: The supraorbital approach to the anterior,
      middle, and posterior fossae through an eyebrow incision offers a favorable rate
      of approach-associated surgical complications and high patient satisfaction with
      cosmetic outcome.

PMID- 24878289
TI  - Relevance of early head CT scans following neurosurgical procedures: an analysis
      of 892 intracranial procedures at Rush University Medical Center.
AB  - OBJECT: Early postoperative head CT scanning is routinely performed following
      intracranial procedures for detection of complications, but its real value
      remains uncertain: so-called abnormal results are frequently found, but active,
      emergency intervention based on these findings may be rare. The authors'
      objective was to analyze whether early postoperative CT scans led to emergency
      surgical interventions and if the results of neurological examination predicted
      this occurrence. METHODS: The authors retrospectively analyzed 892 intracranial
      procedures followed by an early postoperative CT scan performed over a 1-year
      period at Rush University Medical Center and classified these cases according to
      postoperative neurological status: baseline, predicted neurological change,
      unexpected neurological change, and sedated or comatose. The interpretation of CT
      results was reviewed and unexpected CT findings were classified based on
      immediate action taken: Type I, additional observation and CT; Type II, active
      nonsurgical intervention; and Type III, surgical intervention. Results were
      compared between neurological examination groups with the Fisher exact test.
      RESULTS: Patients with unexpected neurological changes or in the sedated or
      comatose group had significantly more unexpected findings on the postoperative CT
      (p < 0.001; OR 19.2 and 2.3, respectively) and Type II/III interventions (p <
      0.001) than patients at baseline. Patients at baseline or with expected
      neurological changes still had a rate of Type II/III changes in the 2.2%-2.4%
      range; however, no patient required an immediate return to the operating room.
      CONCLUSIONS: Over a 1-year period in an academic neurosurgery service, no patient
      who was neurologically intact or who had a predicted neurological change required
      an immediate return to the operating room based on early postoperative CT
      findings. Obtaining early CT scans should not be a priority in these patients and
      may even be cancelled in favor of MRI studies, if the latter have already been
      planned and can be performed safely and in a timely manner. Early postoperative
      CT scanning does not assure an uneventful course, nor should it replace accurate
      and frequent neurological checks, because operative interventions were always
      decided in conjunction with the neurological examination.

PMID- 24878291
TI  - Early sensory protection in reverse end-to-side neurorrhaphy to improve the
      functional recovery of chronically denervated muscle in rat: a pilot study.
AB  - OBJECT: Early innervation by sensory nerves has been proposed to prevent atrophy
      of chronically denervated muscle, but conventional end-to-end (ETE) neurorrhaphy
      has been demonstrated to have adverse effects on muscle contractile function. The
      aim of the present study was to investigate the potential for modified sensory
      nerve protection in reverse end-to-side (ETS) neurorrhaphy as a way of improving
      the functional recovery of denervated muscle. METHODS: Four groups of rats
      underwent surgical denervation of the tibial nerve projecting to the right
      hindlimbs (Group 1, unprotected controls; Group 2, positive control [immediate
      repair without delayed denervation]; Group 3, ETS protected; and Group 4, ETE
      protected). The proximal and distal stumps of the tibial nerve were ligated in
      all animals except for those in the immediate-repair group. Other animals
      underwent denervation without sural nerve protection, or with ETE or ETS
      neurorrhaphy. The ETE- and ETS-protected and unprotected groups underwent an
      additional surgery in which the trimmed proximal and distal tibial nerve stumps
      were sutured together. After 3 months of recovery, the tibial function index was
      determined, and electrophysiological, histological, and morphometric parameters
      were assessed. RESULTS: Significant muscle atrophy was observed in the
      unprotected group, while a well-preserved ultrastructure was observed for the
      gastrocnemius muscle in the ETE- and ETS-protected groups. Enhanced recovery in
      the ETS-protected group was indicated by the tibial function index, motor nerve
      conduction velocity, muscle contractile force tests, and the histological
      results. In contrast, early sensory nerve protection in ETE neurorrhaphy impaired
      the recovery of the regenerated axons and diminished the contractile force of the
      denervated muscle. CONCLUSIONS: Early sensory protection in reverse ETS
      neurorrhaphy is an effective method for improving the functional recovery of
      chronically denervated muscle following peripheral nerve injury in rats.

PMID- 24878290
TI  - Intraoperative cortico-cortical evoked potentials for the evaluation of language
      function during brain tumor resection: initial experience with 13 cases.
AB  - OBJECTIVES: The objective in the present study was to evaluate the usefulness of
      cortico-cortical evoked potentials (CCEP) monitoring for the intraoperative
      assessment of speech function during resection of brain tumors. METHODS:
      Intraoperative monitoring of CCEP was applied in 13 patients (mean age 34 +/- 14
      years) during the removal of neoplasms located within or close to language
      related structures in the dominant cerebral hemisphere. For this purpose strip
      electrodes were positioned above the frontal language area (FLA) and temporal
      language area (TLA), which were identified with direct cortical stimulation
      and/or preliminary mapping with the use of implanted chronic subdural grid
      electrodes. The CCEP response was defined as the highest observed negative peak
      in either direction of stimulation. In 12 cases the tumor was resected during
      awake craniotomy. RESULTS: An intraoperative CCEP response was not obtained in
      one case because of technical problems. In the other patients it was identified
      from the FLA during stimulation of the TLA (7 cases) and from the TLA during
      stimulation of the FLA (5 cases), with a mean peak latency of 83 +/- 15 msec.
      During tumor resection the CCEP response was unchanged in 5 cases, decreased in
      4, and disappeared in 3. Postoperatively, all 7 patients with a decreased or
      absent CCEP response after lesion removal experienced deterioration in speech
      function. In contrast, in 5 cases with an unchanged intraoperative CCEP response,
      speaking abilities after surgery were preserved at the preoperative level, except
      in one patient who experienced not dysphasia, but dysarthria due to pyramidal
      tract injury. This difference was statistically significant (p < 0.01). The time
      required to recover speech function was also significantly associated with the
      type of intraoperative change in CCEP recordings (p < 0.01) and was, on average,
      1.8 +/- 1.0, 5.5 +/- 1.0, and 11.0 +/- 3.6 months, respectively, if the response
      was unchanged, was decreased, or had disappeared. CONCLUSIONS: Monitoring CCEP is
      feasible during the resection of brain tumors affecting language-related cerebral
      structures. In the intraoperative evaluation of speech function, it can be a
      helpful adjunct or can be used in its direct assessment with cortical and
      subcortical mapping during awake craniotomy. It can also be used to predict the
      prognosis of language disorders after surgery and decide on the optimal resection
      of a neoplasm.

PMID- 24878293
TI  - Synthesis of convex hexoctahedral palladium@gold core-shell nanocrystals with
      {431} high-index facets with remarkable electrochemiluminescence activities.
AB  - Convex hexoctahedral nanocrystals have been synthesized through fast growth
      kinetics and the use of cetylpyridinium chloride as a capping agent. Monodisperse
      convex hexoctahedral Pd@Au core-shell nanocrystals with {431} high-index facets
      are obtained at high reaction rates by using high concentrations of ascorbic acid
      in the presence of cetylpyridinium chloride. In contrast, octahedral nanocrystals
      with {111} low-index facets and their {100}-truncated counterparts are formed at
      low ascorbic acid concentrations. The substitute of cetylpyridinium chloride with
      cetyltrimethylammonium chloride leads to the generation of concave trisoctahedral
      Pd@Au core-shell nanocrystals with {331} high-index facets, indicating that
      cetylpyridinium plays an important role in the formation of convex hexoctahedral
      nanocrystals. The as-prepared convex hexoctahedral Pd@Au core-shell nanocrystals
      exhibit remarkable catalytic performances toward electrochemiluminescence
      compared with truncated octahedral and concave trisoctahedral Pd@Au core-shell
      nanocrystals. 

PMID- 24878292
TI  - Gamma Knife surgery for arteriovenous malformations within or adjacent to the
      ventricles.
AB  - OBJECT: The outcomes of stereotactic radiosurgery for arteriovenous malformations
      (AVMs) within or adjacent to the ventricular system are largely unknown. This
      study assessed the long-term outcomes and hemorrhage risks for patients with AVMs
      within this region who underwent Gamma Knife surgery (GKS) at the University of
      Pittsburgh. METHODS: The authors retrospectively identified 188 patients with
      ventricular-region AVMs who underwent a single-stage GKS procedure during a 22
      year interval. The median patient age was 32 years (range 3-80 years), the median
      target volume was 4.6 cm(3) (range 0.1-22 cm(3)), and the median marginal dose
      was 20 Gy (range 13-27 Gy). RESULTS: Arteriovenous malformation obliteration was
      confirmed by MRI or angiography in 89 patients during a median follow-up of 65
      months (range 2-265 months). The actuarial rates of total obliteration were 32%
      at 3 years, 55% at 4 years, 60% at 5 years, and 64% at 10 years. Higher rates of
      AVM obliteration were obtained in the 26 patients with intraventricular AVMs.
      Twenty-five patients (13%) sustained a hemorrhage during the initial latency
      interval after GKS, indicating an annual hemorrhage rate of 3.4% prior to AVM
      obliteration. No patient experienced a hemorrhage after AVM obliteration was
      confirmed by imaging. Permanent neurological deficits due to adverse radiation
      effects developed in 7 patients (4%). CONCLUSIONS: Although patients in this
      study demonstrated an elevated hemorrhage risk that remained until complete
      obliteration, GKS still proved to be a generally safe and effective treatment for
      patients with these high-risk intraventricular and periventriclar AVMs.

PMID- 24878294
TI  - Systematic review of the prevalence and characteristics of battle casualties from
      NATO coalition forces in Iraq and Afghanistan.
AB  - BACKGROUND: The North Atlantic Treaty Organization (NATO) coalition forces remain
      heavily committed on combat operations overseas. Understanding the prevalence and
      characteristics of battlefield injury of coalition partners is vital to combat
      casualty care performance improvement. The aim of this systematic review was to
      evaluate the prevalence and characteristics of battle casualties from NATO
      coalition partners in Iraq and Afghanistan. The primary outcome was mechanism of
      injury and the secondary outcome anatomical distribution of wounds. METHODS: This
      systematic review was performed based on all cohort studies concerning prevalence
      and characteristics of battlefield injury of coalition forces from Iraq and
      Afghanistan up to December 20th 2013. Studies were rated on the level of evidence
      provided according to criteria by the Centre for Evidence Based Medicine in
      Oxford. The methodological quality of observational comparative studies was
      assessed by the modified Newcastle-Ottawa Scale. RESULTS: Eight published
      articles, encompassing a total of n=19,750 battle casualties, were systematically
      analyzed to achieve a summated outcome. There was heterogeneity among the
      included studies and there were major differences in inclusion and exclusion
      criteria regarding the target population among the included trials, introducing
      bias. The overall distribution in mechanism of injury was 18% gunshot wounds, 72%
      explosions and other 10%. The overall anatomical distribution of wounds was head
      and neck 31%, truncal 27%, extremity 39% and other 3%. CONCLUSIONS: The mechanism
      of injury and anatomical distribution of wounds observed in the published
      articles by NATO coalition partners regarding Iraq and Afghanistan differ from
      previous campaigns. There was a significant increase in the use of explosive
      mechanisms and a significant increase in the head and neck region compared with
      previous wars.

PMID- 24878295
TI  - [Erdheim-Chester disease].
AB  - Erdheim-Chester disease is a rare and orphan disease. Despite having been
      overlooked previously, numerous new cases have been diagnosed more recently. The
      number of Erdheim-Chester disease cases reported has increased substantially:
      more than 300 new cases have been published in the past 10 years. This situation
      is mainly a result of the generally better awareness among pathologists,
      radiologists, and clinicians of various aspects of this rare disease. The field
      has been particularly active in the last few years, with evidence of the efficacy
      of interferon-alpha, the description of a systemic pro-inflammatory cytokine
      signature, and most recently, reports of the dramatic efficacy of BRAF inhibition
      in severe, BRAF(V600E) mutation-associated cases of Erdheim-Chester disease.
      Also, BRAF mutations have been found in more than half of the patients with
      Erdheim-Chester disease who were tested. Detailed elucidation of the pathogenesis
      of the disease is likely to lead to the development of better targeted and more
      effective therapies. 

PMID- 24878296
TI  - Association between cannabis use and schizotypal dimensions--a meta-analysis of
      cross-sectional studies.
AB  - Cannabis consumption can cause abuse and dependence and increase risk of
      developing psychiatric and somatic disorders. Several literature reviews explored
      the link between cannabis consumption and schizophrenia but none summarized the
      rich literature on cannabis and psychometric schizotypy. The aim of our review is
      to synthesize data from studies that explored the association between cannabis
      consumption and schizoptypal dimensions. A systematic review of the literature
      and, when needed, contact with the authors, allowed us to gather data from 29
      cross-sectional studies. We compared schizotypy scores between subjects that
      never used cannabis and subjects that used it at least once ("never vs. ever")
      and between current users and subjects that do not use cannabis currently
      ("current vs. other"). We conducted separate analyses for total schizotypy score
      and each of the three classical schizotypal dimensions (positive, negative,
      disorganized). For all eight comparisons, the cannabis group ("ever" or
      "current") had higher schizotypy scores. Differences were in the small or medium
      range and, with the exception of the negative score in the current vs. other
      comparison, statistically significant. Cannabis consumption is associated with
      increased schizotypal traits. More research, using different approaches (e.g.
      longitudinal studies) is needed to explore the cause of this association. 

PMID- 24878298
TI  - Personality profiles in Eating Disorders: further evidence of the clinical
      utility of examining subtypes based on temperament.
AB  - Despite recent modifications to the DSM-V diagnostic criteria for Eating
      Disorders (ED; American Psychiatric Association, 2013), sources of variability in
      the clinical presentation of ED patients remain poorly understood. Consistent
      with previous research that has used underlying personality dimensions to
      identify distinct subgroups of ED patients, the present study examined (1)
      whether we could identify clinically meaningful subgroups of patients based on
      temperamental factors including Behavioral Inhibition (BIS), Behavioral
      Activation (BAS) and Effortful Control (EC), and (2) whether the identified
      subgroups would also differ with respect to ED, Axis-I and Axis-II
      psychopathology. One hundred and forty five ED inpatients participated in this
      study. Results of a k-means analysis identified three distinct groups of
      patients: an Overcontrolled/Inhibited group (n=53), an
      Undercontrolled/Dysregulated group (n=58) and a Resilient group (n=34). Further,
      group comparisons revealed that patients in the Undercontrolled/Dysregulated
      group demonstrated more severe symptoms of bulimia, hostility and Cluster B
      Personality Disorders compared to the other groups, while patients in the
      Resilient group demonstrated the least severe psychopathology. These findings
      have important implications for understanding how individual differences in
      personality may impact patterns of ED symptoms and co-occurring psychopathology
      in patients with ED. 

PMID- 24878297
TI  - Differences in coping, self-efficacy, and external control beliefs between
      patients at-risk for psychosis and patients with first-episode psychosis.
AB  - Patients with first-episode psychosis (FEP) often show dysfunctional coping
      patterns, low self-efficacy, and external control beliefs that are considered to
      be risk factors for the development of psychosis. Therefore, these factors should
      already be present in patients at-risk for psychosis (AR). We compared
      frequencies of deficits in coping strategies (Stress-Coping-Questionnaires, SVF
      120/SVF-KJ), self-efficacy, and control beliefs (Competence and Control Beliefs
      Questionnaire, FKK) between AR (n=21) and FEP (n=22) patients using a cross
      sectional design. Correlations among coping, self-efficacy, and control beliefs
      were assessed in both groups. The majority of AR and FEP patients demonstrated
      deficits in coping skills, self-efficacy, and control beliefs. However, AR
      patients more frequently reported a lack of positive coping strategies, low self
      efficacy, and a fatalistic externalizing bias. In contrast, FEP patients were
      characterized by being overly self-confident. These findings suggest that
      dysfunctional coping, self-efficacy, and control beliefs are already evident in
      AR patients, though different from those in FEP patients. The pattern of deficits
      in AR patients closely resembles that of depressive patients, which may reflect
      high levels of depressiveness in AR patients. Apart from being worthwhile
      treatment targets, these coping and belief patterns are promising candidates for
      predicting outcome in AR patients, including the conversion to psychosis. 

PMID- 24878299
TI  - Intact alternation performance in high lethality suicide attempters.
AB  - Suicide attempters often perform poorly on tasks linked to ventral prefrontal
      cortical (VPFC) function. Object Alternation (OA) - a VPFC probe - has not been
      used in these studies. In this study, currently depressed medication-free past
      suicide attempters whose most severe attempt was of high (n=31) vs. low (n=64)
      lethality, 114 medication-free depressed non-attempters, and 86 non-patients
      completed a computerized OA task. Participants also completed comparison tasks
      assessing the discriminant validity of OA (Wisconsin Card Sort), its concurrent
      validity relative to tasks associated with past attempt status (computerized
      Stroop task, Buschke Selective Reminding Test), and its construct validity as a
      VPFC measure (Go-No Go and Iowa Gambling Task). Against expectations, high
      lethality suicide attempters - the majority of whom used non-violent methods in
      their attempts with some planning - outperformed other depressed groups on OA,
      with no group differences observed on Wisconsin Card Sort. Despite intact
      performance on OA, past attempters exhibited deficits on the Stroop and Buschke.
      OA performance was associated with performance on Go-No Go and Iowa Gambling,
      confirming that OA measures a similar construct. VPFC dysfunction may not be a
      characteristic of all suicide attempters, especially those who make more
      carefully planned, non-violent - though potentially lethal - attempts. 

PMID- 24878300
TI  - Characterizing analgesic use during air medical transport of injured children.
AB  - BACKGROUND: Pain management is an important aspect of emergency care for children
      suffering traumatic injuries. OBJECTIVES: The objectives of this study were to
      characterize analgesic administration to injured children during air medical
      transport, to describe factors associated with analgesic use, and to examine the
      effects of patient race on analgesia. METHODS: We used electronic records for
      patients transported by a regional air medical transport agency. We
      retrospectively examined data from 2003-2012 for patients <= 15 years old
      suffering traumatic injuries. We used bivariable analyses to identify
      associations for multivariable logistic regression models to determine factors
      associated with our outcomes -documentation of pain score and analgesic
      administration. RESULTS: Of 5,057 patients, the median age was 8 (IQR 3-12)
      years. The majority of patients were male (66%, 95% CI 64-66%), were white non
      Hispanic (83%, 95% CI 82-84%), and had no pain score documented (61%, 95% CI 60
      62%). While only 15% of patients received analgesics overall, 70% with an initial
      pain score >= 5 received analgesics. In unadjusted models, non-white race was
      associated with lower odds of having a pain score documented (OR 0.52, 95% CI
      0.44-0.62) and receiving analgesics (OR 0.64, 95% CI 0.50-0.82). After adjusting
      for confounders, there was no evidence of racial differences in pain management.
      Multivariable analysis revealed that younger age, lack of intravenous access,
      higher Glasgow Coma Scale, systolic blood pressure <100, transportation from the
      scene, initial pain score <5, and not having a pain score documented were
      associated with lower odds of receiving analgesics. CONCLUSIONS: Few pediatric
      patients had pain scores documented and fewer received analgesics during air
      medical transport for injuries. Racial differences in analgesia seen in
      unadjusted analyses did not persist after controlling for confounders. Resources,
      training, and appropriate pain management protocols should be made available to
      facilitate pain assessment in children as a strategy for increasing appropriate
      analgesic use during transport.

PMID- 24878301
TI  - Distribution and bioaccumulation of polychlorinated biphenyls and organochlorine
      pesticides residues in sediments and Manila clams (Ruditapes philippinarum) from
      along the Mid-Western coast of Korea.
AB  - The distribution and bioaccumulation features of PCBs, DDTs, and HCHs were
      investigated in the sediments and Manila clams collected from along the Mid
      Western coast of Korea. The measured concentrations of SigmaPCBs, SigmaDDTs and
      SigmaHCHs were 1.08-3.5, 0.12-0.35 and 0.090-0.30 ng g(-1) dw in sediment, and 33
      390, 7.4-46 and 6.3-27 ng g(-1) lipid in Manila clam, respectively. Their levels
      were found to be relatively lower than those of other contaminated areas and the
      consumption of Manila clam from these areas seems to be safe for human health
      according to calculated lifetime cancer risk and hazard indices. The SigmaPCBs
      and SigmaDDTs concentrations in sediments showed a significant relationship to
      those in clams. The significant correlation was observed between BSAF in clams
      and Kow for each PCB congeners and DDT metabolites. These findings support that
      the PCBs and DDTs levels, which are highly hydrophobic chemicals, in clam reflect
      the sediment pollution through bioaccumulation.

PMID- 24878302
TI  - Interactive effects of hypoxia and polybrominated diphenyl ethers (PBDEs) on
      microbial community assembly in surface marine sediments.
AB  - Hypoxia alters the oxidation-reduction balance and the biogeochemical processes
      in sediments, but little is known about its impacts on the microbial community
      that is responsible for such processes. In this study, we investigated the
      effects of hypoxia and the ubiquitously dispersed flame-retardant BDE47 on the
      bacterial communities in marine surface sediments during a 28-days microcosm
      experiment. Both hypoxia and BDE47 alone significantly altered the bacterial
      community and reduced the species and genetic diversity. UniFrac analysis
      revealed that BDE47 selected certain bacterial species and resulted in major
      community shifts, whereas hypoxia changed the relative abundances of taxa,
      suggesting slower but nonetheless significant community shifts. These two
      stressors targeted mostly different taxa, but they both favored Bacteroidetes and
      suppressed Gammaproteobacteria. Importantly, the impacts of BDE47 on bacterial
      communities were different under hypoxic and normoxic conditions, highlighting
      the need to consider risk assessments for BDE47 in a broader context of
      interaction with hypoxia. 

PMID- 24878303
TI  - Distribution of resting cysts of the potentially toxic dinoflagellate Alexandrium
      pseudogonyaulax in recently-deposited sediment within Bizerte Lagoon
      (Mediterranean coast, Tunisia).
AB  - This study investigated the spatial distribution of Alexandrium pseudogonyaulax
      resting cysts in recently-deposited sediment of Bizerte lagoon (South-Western
      Mediterranean, Tunisia). This lagoon is the subject of many anthropogenic
      impacts, such as holding important fishing and aquaculture activities. A.
      pseudogonyaulax has been shown to produce Goniodomin A, which is a biologically
      active compound. We showed that this dinoflagellate produces two types of resting
      cysts, which could be distinguished by the presence or the absence of a
      paratabulate wall. The average cyst density across the whole lagoon was rather
      high, reaching 639 cysts g(-1) of dry sediment (DS). Cyst densities varied widely
      among the sampled stations, with the highest density of 1685 cyst g(-1)DS being
      recorded at station 51 near a mussel farm. With respect to sediment
      characteristics, the highest cyst densities were found within silty sediments
      with high water content values. The distribution of A. pseudongoyaulax cysts in
      Bizerte lagoon appears to be related to hydrodynamic factors.

PMID- 24878304
TI  - Seaweeds and plastic debris can influence the survival of faecal indicator
      organisms in beach environments.
AB  - The revised Bathing Water Directive (rBWD) introduces more stringent standards
      for microbial water quality and promotes more pro-active management of the beach
      environment through the production of a bathing water profile (BWP). The aim of
      this study was to determine whether living seaweeds in the littoral zone are
      colonised by faecal indicator organisms (FIOs), and to quantify the survival
      dynamics of waterborne Escherichia coli in microcosms containing senescing
      seaweeds. Living seaweed (Fucus spiralis) was not associated with FIO
      colonisation, although could be providing a protected environment in the
      underlying sand. Senescing seaweeds enhanced waterborne E. coli survival compared
      to plastic debris, with the brown seaweed Laminaria saccharina facilitating
      greater E. coli persistence than either Chondrus crispus or Ulva lactuca. This
      has important implications for FIO survival on bathing beaches as the majority of
      beach-cast biomass is composed of brown seaweeds, which could support significant
      levels of FIOs. 

PMID- 24878305
TI  - Trace element concentrations in barramundi (Lates calcarifer) collected along the
      coast of Vietnam.
AB  - We determined concentrations of 23 trace elements (TEs), and stable carbon and
      nitrogen isotope (delta(13)C and delta(15)N) signatures in barramundi (Lates
      calcarifer) specimens collected along the coast of Vietnam in the Northern (NCZ),
      Central (CCZ) and Southern (SCZ) zones in the period 2007-2010. A combination of
      delta(13)C and delta(15)N signatures provided insight into ontogenetic shifts in
      barramundi foraging choices. There were clear zone-dependent differences in Mn,
      As, Sr and Tl concentrations; levels of Tl were highest in the NCZ, As in the
      CCZ, and Mn and Sr in the SCZ. Lowest concentrations of Rb occurred in the NCZ,
      Bi was lowest in the CCZ, and Cd and Cs were lowest in the SCZ. delta(15)N values
      significantly increased with increasing Zn, Se, Sn and Cs. Concentrations of TEs
      in barramundi from Vietnam were below worldwide guidelines for human consumption.

PMID- 24878306
TI  - Anmindenols A and B, inducible nitric oxide synthase inhibitors from a marine
      derived Streptomyces sp.
AB  - Anmindenols A (1) and B (2), inhibitors of inducible nitric oxide synthase
      (iNOS), were isolated from a marine-derived bacterium Streptomyces sp. Their
      chemical structures were elucidated by interpreting various spectroscopic data,
      including IR, MS, and NMR. Anmindenols A and B are sesquiterpenoids possessing an
      indene moiety with five- and six-membered rings derived from isoprenyl units. The
      absolute configuration of C-4 in anmindenol B was determined by electronic
      circular dichroism (ECD) of a dimolybdenum complex. Anmindenols A (1) and B (2)
      inhibited nitric oxide production in stimulated RAW 264.7 macrophage cells with
      IC50 values of 23 and 19 MUM, respectively. 

PMID- 24878307
TI  - Confocal microscopy analysis of corneal changes after photorefractive keratectomy
      plus cross-linking for keratoconus: 4-year follow-up.
AB  - PURPOSE: To analyze corneal confocal microscopy changes after combined
      photorefractive keratectomy (PRK) plus the cross linking (CXL) procedure. DESIGN:
      Prospective interventional case series. METHODS: At the Department of Basic
      Medical Sciences, Neuroscience, and Sense Organs of the University of Bari, Bari,
      Italy, 17 eyes of 17 patients with progressive keratoconus underwent confocal
      microscopy examination before and after 1, 3, 6, 12, 18, and 48 months following
      PRK plus the CXL procedure. The main outcome measures were mean superficial
      epithelial cell density; mean basal epithelial cell density; mean anterior, mid
      and posterior keratocyte density; qualitative analysis of stromal backscatter;
      sub-basal and stromal nerve density parameters; and mean endothelial cell
      density. RESULTS: During the 4-year follow-up, the mean superficial epithelial
      cell density, mean basal epithelial cell density and mean endothelial cell
      density remained unchanged (P > 0.05). The anterior mid-stromal keratocyte
      density showed a significant decrease (P < 0.05) as compared with preoperative
      values, and the posterior stromal keratocyte density showed a significant
      increase at 1 and 3 months of follow-up. Sub-basal and stromal nerve density
      parameters were significantly decreased until postoperative month 6 (P < 0.05 at
      1, 3, and 6 months) and then tended to increase up to preoperative values by the
      18th postoperative month. CONCLUSION: Corneal changes after the PRK plus CXL
      procedures seem to be pronounced and long lasting as far as keratocyte density of
      the anterior and mid stroma is concerned. Sub-basal nerve densities tend to reach
      preoperative values 6 months after surgery.

PMID- 24878308
TI  - Visual acuity and subfoveal choroidal thickness: the Beijing Eye Study.
AB  - PURPOSE: To examine the association between best corrected visual acuity (BCVA)
      and subfoveal choroidal thickness. DESIGN: Population-based study. METHODS: The
      Beijing Eye Study 2011 included 3468 subjects with ages of 50+ years. The
      participants underwent an ophthalmologic examination including spectral-domain
      optical coherence tomography with enhanced depth imaging for measurement of
      choroidal thickness. BCVA was measured as logarithm of the minimal angle of
      resolution. RESULTS: Of the 3468 participants, choroidal measurements were
      available for 3233 (93.2%) subjects. In multivariate analysis, better BCVA was
      significantly associated with thicker subfoveal choroid (P < 0.001) in general
      and a subfoveal choroid thicker than 30 MUm (P < 0.001) in particular, after
      adjusting for younger age (P < 0.001), higher level of education (P < 0.001),
      taller body stature (P < 0.001), higher body mass index (P = 0.005), absence of
      glaucoma (P = 0.001), absence of diabetic retinopathy (P < 0.001), absence of
      late-stage age-related macular degeneration (P < 0.001), and axial length shorter
      than 26.0 mm (P < 0.001) (correlation coefficient r:0.56). If eyes with glaucoma,
      diabetic retinopathy, late-stage age-related macular degeneration or myopic
      retinopathy were excluded, better BCVA was still significantly associated with
      thicker subfoveal choroid (P < 0.001) and subfoveal choroid thicker than 30 MUm
      (P < 0.001) in multivariate analysis. In a reverse manner, thicker subfoveal
      choroid was associated with better BCVA (P < 0.001) after adjusting for younger
      age (P < 0.001), male gender (P < 0.001), longer axial length (P < 0.001), and
      higher corneal curvature radius (P < 0.001). CONCLUSIONS: Better visual acuity is
      strongly associated with thicker subfoveal choroid independent of additional
      factors, such as age, axial length, education level, and major ocular diseases.

PMID- 24878310
TI  - Quasiclassical trajectory study of the C(1D) + H2 -> CH + H reaction on a new
      global ab initio potential energy surface.
AB  - Quasiclassical trajectory (QCT) calculations have been performed on a new global
      ab initio potential energy surface (PES) for the singlet ground state (1(1)A') of
      the CH2 reactive system. Our new PES can give a very good description of the well
      and asymptote regions, and particularly regions around conical intersections
      (CIs) and of van der Waals (vdW) interactions. The integral cross sections,
      differential cross sections, and product rovibrational state distributions for
      the C((1)D) + H2 -> CH + H reaction have been investigated in a wide range of
      collision energies. The present integral cross sections are much larger than the
      previous QCT results at low collision energies, which can be attributed to the
      differences of the PESs in the regions around the CIs and vdW complexes. The
      thermal rate coefficients in the temperature range 200-1500 K have also been
      calculated and very good agreement with experiment is obtained. 

PMID- 24878309
TI  - Ultrastructural changes of the vitreoretinal interface during long-term follow-up
      after removal of the internal limiting membrane.
AB  - PURPOSE: To investigate long-term ultrastructural changes in the retina after
      internal limiting membrane (ILM) peeling through the examination of morphologic
      changes 3 years after vitrectomy in cynomolgus monkeys. DESIGN: Laboratory
      investigation. METHODS: Pars plana vitrectomy was performed, followed by ILM
      peeling, in 2 primate eyes. Ultrastructural changes were investigated using light
      microscopy and transmission and scanning electron microscopy 3 years after ILM
      peeling. RESULTS: The remaining posterior vitreous and ILM-peeled areas were
      clearly recognized after the long-term follow-up. The exposed Muller cell
      processes were partially damaged, while regenerative spindle-shaped Muller cell
      processes developed, covering most of the retina. Notably, the nerve fiber layer
      was found to be uncovered and exposed to the vitreous space owing to misdirection
      of glial wound healing in some parts. In these areas, glial wound healing
      occurred beneath the nerve fiber layer. Although the glial cells covered the
      damaged areas, there was no apparent ILM regeneration in the shape of a
      continuous flat sheet, with the exception of accumulated deposits of basement
      membrane materials. CONCLUSIONS: Although the retinal structures were well
      preserved after ILM peeling, ILM peeling resulted in mild damage to the
      vitreoretinal interface, which was not completely restored even after 3 years.
      The multilinear shape of the exposed nerve fiber may explain the previously
      reported dissociated optic nerve fiber layer appearance. The glial cells produced
      basement membrane materials around their processes, although they did not restore
      the ILM as a flat sheet.

PMID- 24878311
TI  - The role of an alpha animal in changing environmental conditions.
AB  - The maintenance and development of conservation areas by grazing of large
      herbivores, such as Przewalski's horses, is common practice. Several nature
      conservation areas house male bachelor groups of this species. When males are
      needed for breeding they are removed from the groups, often without considering
      group compositions and individual social positions. However, alpha animals are
      needed for ensuring group stability and decision making in potentially dangerous
      situations in several species. To investigate the role of the alpha male in a
      bachelor group, we observed the behaviour of five Przewalski's horse males during
      the enlargement of their enclosure. We analyzed the group's social structure and
      movement orders, as well as the animals' connectedness, activity budgets, and
      whether they moved with preferred group members and how factors such as social
      rank influenced the horses' behaviour. We also investigated the excretion of
      glucocorticoid metabolites (GCM) via faeces of the horses while exploring a new
      area as a parameter of glucocorticoid production. Our results show that the alpha
      male is important for a bachelor group in changing environmental conditions. The
      alpha male had the highest level of connectedness within the group. When
      exploring the new environment, its position in the group changed from previously
      being the last to being the first. Furthermore the whole group behaviour changed
      when exploring the new area. The stallions showed reduced resting behavior,
      increased feeding and did not stay close to each other. We found that the
      excretion of glucocorticoid metabolites of most horses rose only marginally
      during the first days on the new area while only the alpha male showed a
      significant increased amount of glucocorticoid production during the first day of
      the enclosure enlargement. 

PMID- 24878312
TI  - Capacity of novelty-induced locomotor activity and the hole-board test to predict
      sensitivity to the conditioned rewarding effects of cocaine.
AB  - Novelty-seeking in rodents, defined as enhanced specific exploration of novel
      situations, is considered to predict the response of animals to drugs of abuse
      and, thus, allow "drug-vulnerable" individuals to be identified. The main
      objective of this study was to assess the predictive ability of two well-known
      paradigms of the novelty-seeking trait - novelty-induced locomotor activity
      (which distinguishes High- and Low-Responder mice, depending on their motor
      activity) and the hole-board test (which determines High- and Low-Novelty Seeker
      mice depending on the number of head dips they perform) - to identify subjects
      that would subsequently be more sensitive to the conditioned rewarding effects of
      cocaine in a population of young adult (PND 56) and adolescent (PND 35) OF1 mice
      of both sexes. Conditioned place preference (CPP), a useful tool for evaluating
      the sensitivity of individuals to the incentive properties of addictive drugs,
      was induced with a sub-threshold dose of cocaine (1 mg/kg, i.p.). Our results
      showed that novelty-induced motor activity had a greater predictive capacity to
      identify "vulnerable-drug" individuals among young-adult mice (PND 56), while the
      hole-board test was more effective in adolescents (PND 35). High-NR young-adults,
      which presented higher motor activity in the first ten minutes of the test
      (novelty-reactivity), were 3.9 times more likely to develop cocaine-induced CPP
      than Low-NR young-adults. When total activity (1h) was evaluated (novelty
      habituation), only High-R (novelty-non-habituating) young-adult male and Low-R
      (novelty-habituating) female mice produced a high conditioning score. However,
      only High-Novelty Seeker male and female adolescents and Low-Novelty Seeker
      female young-adult animals (according to the hole-board test), acquired cocaine
      induced CPP. These findings should contribute to the development of screening
      methods for identifying at-risk human drug users and prevention strategies for
      those with specific vulnerabilities.

PMID- 24878313
TI  - Anticipatory and foraging behaviors in response to palatable food reward in
      chickens: effects of dopamine D2 receptor blockade and domestication.
AB  - Behaviors associated with anticipation and search for palatable food may provide
      information about dopaminergic reward processes and positive motivational affect
      in animals. The overall aim was to investigate the involvement of dopamine
      signaling in the regulation of cue-induced anticipation and search for palatable
      food reward in chicken, and whether domestication has affected expression of
      reward-related behaviors. The specific aims were to describe effects of mealworms
      (palatable food for hens) and haloperidol (a dopamine D2 antagonist) on foraging
      behaviors and cue-induced anticipatory behaviors in Red Junglefowl (RJF; the wild
      ancestor of modern laying hens) and a white layer hybrid (LSL). RJF (n=26) and
      LSL (n=20) were initially trained on a conditioning schedule to anticipate
      mealworms (unconditioned stimulus; US) 25s after exposure to a red light
      (conditioned stimulus; CS). For the experiment, hens received haloperidol or
      saline injections 30 min before exposure to one CS+US combination. Behavior was
      registered 10 min before CS and 10 min after US (foraging behaviors), and during
      the CS-US interval (anticipatory behaviors). Higher frequencies of CS-induced
      anticipatory head movements, faster approach to rewards, and higher frequency of
      foraging behaviors were found in LSL compared to RJF. Haloperidol suppressed CS
      induced head movements in both breeds, and the frequency of foraging behaviors
      after reward delivery. The results support a role of dopamine signaling in the
      regulation of reward processes in chickens, and suggest that domestication has
      changed the threshold for perceiving food incentives and/or for expressing reward
      related behaviors that may be indicative of positive motivational affect in hens.

PMID- 24878314
TI  - Early adolescent stress alters behavior and the HPA axis response in male and
      female adult rats: the relevance of the nature and duration of the stressor.
AB  - Adolescence is a period of transition from childhood to adulthood that involves
      the maturation of social and cognitive behavior. The activation of the stress
      system during this phase can lead to long-lasting adverse effects. We aimed to
      verify whether the nature and duration of stressors applied in adolescent female
      and male rats would alter their exploratory behavior and stress responses as
      adults. Wistar rats on day P26 were divided into groups that were subjected to 1
      (acute) or 7 (chronic) insulin or lipopolysaccharide (LPS) injections or
      restraint stress for 1 h. At P60, the rats were subjected to the elevated plus
      maze, and at P61, they were subjected to 30 min of restraint stress after which
      plasma samples and brains were collected. LPS acute injection promoted anxiolytic
      effects in male adults. Acute LPS treatment and acute or chronic restraint
      induced anxiolytic behavior in female adults. The administration of adolescent
      chronic stimuli to males decreased the adult plasma corticosterone (CORT) and
      progesterone levels after restraint. Adolescent acute restraint or LPS injection
      decreased the CORT response in female adults. The adult neuronal activation of
      the corticotrophin-releasing hormone and vasopressin on the paraventricular
      nucleus did not vary according to the type of adolescent stress or sex. Our
      results indicate that both adult behavior and the glucocorticoid stress response
      are affected differently in males versus females by adolescent stress. The
      duration of stressors had a greater effect on the CORT and progesterone response
      in males, whereas the nature of the stressor had a greater effect on exploratory
      behavior in females.

PMID- 24878315
TI  - Avian reflex and electroencephalogram responses in different states of
      consciousness.
AB  - Defining states of clinical consciousness in animals is important in veterinary
      anaesthesia and in studies of euthanasia and welfare assessment at slaughter. The
      aim of this study was to validate readily observable reflex responses in relation
      to different conscious states, as confirmed by EEG analysis, in two species of
      birds under laboratory conditions (35-week-old layer hens (n=12) and 11-week-old
      turkeys (n=10)). We evaluated clinical reflexes and characterised
      electroencephalograph (EEG) activity (as a measure of brain function) using
      spectral analyses in four different clinical states of consciousness: conscious
      (fully awake), semi-conscious (sedated), unconscious-optimal (general
      anaesthesia), unconscious-sub optimal (deep hypnotic state), as well as
      assessment immediately following euthanasia. Jaw or neck muscle tone was the most
      reliable reflex measure distinguishing between conscious and unconscious states.
      Pupillary reflex was consistently observed until respiratory arrest. Nictitating
      membrane reflex persisted for a short time (<1 min) after respiratory arrest and
      brain death (isoelectric EEG). The results confirm that the nictitating membrane
      reflex is a conservative measure of death in poultry. Using spectral analyses of
      the EEG waveforms it was possible to readily distinguish between the different
      states of clinical consciousness. In all cases, when birds progressed from a
      conscious to unconscious state; total spectral power (PTOT) significantly
      increased, whereas median (F50) and spectral edge (F95) frequencies significantly
      decreased. This study demonstrates that EEG analysis can differentiate between
      clinical states (and loss of brain function at death) in birds and provides a
      unique integration of reflex responses and EEG activity.

PMID- 24878318
TI  - When does this cortical area drop off? Principal component structuring of the EEG
      spectrum yields yes-or-no criteria of local sleep onset.
AB  - The traditional sleep scoring approach has been invented long before the
      recognition of strictly local nature of the sleep process. It considers sleep as
      a whole-organism behavior state, and, thus, it cannot be used for identification
      of sleep onset in a separate brain region. Therefore, this paper was aimed on
      testing whether the practically useful, simple and reliable yes-or-no criterion
      of sleep onset in a particular cortical region might be developed through
      applying principal component analysis to the electroencephalographic (EEG)
      spectra. The resting EEG was recorded with 2-hour intervals throughout 43-61-hour
      prolongation of wakefulness, and during 12 20-minute attempts to nap in the
      course of 24-hour wakefulness (15 and 18 adults, respectively). The EEG power
      spectra were averaged on 1-min intervals of each resting EEG record and on 1-min
      intervals of each napping attempt, respectively. Since we earlier demonstrated
      that scores on the first and second principal components of the EEG spectrum
      exhibit dramatic changes during the sleep onset period, a zero-crossing buildup
      of the first score and a zero-crossing decline of the second score were examined
      as possible yes-or-no markers of regional sleep onsets. The results suggest that,
      irrespective of electrode location, sleep onset criterion and duration of
      preceding wakefulness, a highly significant zero-crossing decline of the second
      principal component score always occurred within 1-minute interval of transition
      from wakefulness to sleep. Therefore, it was concluded that such zero-crossing
      decline can serve as a reliable, simple, and practically useful yes-or-no marker
      of drop off event in a given cortical area. 

PMID- 24878317
TI  - Domestication effects on behavioural and hormonal responses to acute stress in
      chickens.
AB  - Comparative studies have shown that alterations in physiology, morphology and
      behaviour have arisen due to the domestication. A driving factor behind many of
      the changes could be a shift in stress responses, with modified endocrine and
      behavioural profiles. In the present study we compared two breeds of chicken
      (Gallus gallus), the domestic White Leghorn (WL) egg laying breed and its
      ancestor, the Red Junglefowl (RJF). Birds were exposed to an acute stress event,
      invoked by 3 or 10 min of physical restraint. They were then continuously
      monitored for the effects on a wide range of behaviours during a 60 min recovery
      phase. Blood samples were collected from the chicken at baseline, and after 10
      and 60 min following a similar restraint stress, and the samples were analyzed
      for nine endogenous steroids of the HPA and HPG axes. Concentration of the
      steroids was determined using validated liquid chromatography tandem mass
      spectrometry methods. In RJF, an immediate behavioural response was observed
      after release from restraint in several behaviours, with a relatively fast return
      to baseline within 1h. In WL, some behaviours were affected for a longer period
      of time, and others not at all. Concentrations of corticosterone increased more
      in RJF, but returned faster to baseline compared to WL. A range of baseline
      levels for HPG-related steroids differed between the breeds, and they were
      generally more affected by the stress in WL than in RJF. In conclusion, RJF
      reacted stronger both behaviourally and physiologically to the restraint stress,
      but also recovered faster. This would appear to be adaptive under natural
      conditions, whereas the stress recovery of domesticated birds has been altered by
      domestication and breeding for increased reproductive output.

PMID- 24878316
TI  - Inhibition of food intake by PACAP in the hypothalamic ventromedial nuclei is
      mediated by NMDA receptors.
AB  - Central injections of pituitary adenylate cyclase-activating polypeptide (PACAP)
      into the ventromedial nuclei (VMN) of the hypothalamus produce hypophagia that is
      dependent upon the PAC1 receptor; however, the signaling downstream of this
      receptor in the VMN is unknown. Though PACAP signaling has many targets, this
      neuropeptide has been shown to influence glutamate signaling in several brain
      regions through mechanisms involving NMDA receptor potentiation via activation of
      the Src family of protein tyrosine kinases. With this in mind, we examined the
      Src-NMDA receptor signaling pathway as a target for PACAP signaling in the VMN
      that may mediate its effects on feeding behavior. Under nocturnal feeding
      conditions, NMDA receptor antagonism prior to PACAP administration into the VMN
      attenuated PACAP-mediated decreases in feeding suggesting that glutamatergic
      signaling via NMDA receptors is necessary for PACAP-induced hypophagia.
      Furthermore, PACAP administration into the VMN resulted in increased tyrosine
      phosphorylation of the GluN2B subunit of the NMDA receptor, and inhibition of Src
      kinase activity also blocked the effects of PACAP administration into the VMN on
      feeding behavior. These results indicate that PACAP neurotransmission in the VMN
      likely augments glutamate signaling by potentiating NMDA receptors activity
      through the tyrosine phosphorylation events mediated by the Src kinase family,
      and modulation of NMDA receptor activity by PACAP in the hypothalamus may be a
      primary mechanism for its regulation of food intake. 

PMID- 24878319
TI  - Cost-effectiveness of uterine-preserving procedures for the treatment of uterine
      fibroid symptoms in the USA.
AB  - OBJECTIVE: To evaluate the cost-effectiveness of the following three treatments
      of uterine fibroids in a population of premenopausal women who wish to preserve
      their uteri: myomectomy, magnetic resonance-guided focused ultrasound (MRgFUS)
      and uterine artery embolization (UAE). MATERIALS & METHODS: A decision analytic
      Markov model was constructed. Cost-effectiveness was calculated in terms of US$
      per quality-adjusted life year (QALY) over 5 years. Two types of costs were
      calculated: direct costs only, and the sum of direct and indirect (productivity)
      costs. Women in the hypothetical cohort were assessed for treatment type
      eligibility, were treated based on eligibility, and experienced adequate or
      inadequate symptom relief. Additional treatment (myomectomy) occurred for
      inadequate symptom relief or recurrence. Sensitivity analysis was conducted to
      evaluate uncertainty in the model parameters. RESULTS:  In the base case,
      myomectomy, MRgFUS and UAE had the following combinations of mean cost and mean
      QALYs, respectively: US$15,459, 3.957; US$15,274, 3.953; and US$18,653, 3.943.
      When incorporating productivity costs, MRgFUS incurred a mean cost of US$21,232;
      myomectomy US$22,599; and UAE US$22,819. Using probabilistic sensitivity analysis
      (PSA) and excluding productivity costs, myomectomy was cost effective at almost
      every decision threshold. Using PSA and incorporating productivity costs,
      myomectomy was cost effective at decision thresholds above US$105,000/QALY;
      MRgFUS was cost effective between US$30,000 and US$105,000/QALY; and UAE was cost
      effective below US$30,000/QALY. CONCLUSION: Myomectomy, MRgFUS, and UAE were
      similarly effective in terms of QALYs gained. Depending on assumptions about
      costs and willingness to pay for additional QALYs, all three treatments can be
      deemed cost effective in a 5-year time frame.

PMID- 24878320
TI  - The relationship between bifidobacteria and allergic asthma and/or allergic
      dermatitis: a prospective study of 0-3 years-old children in Turkey.
AB  - Bifidobacteria are beneficial bacteria for humans. These bacteria are
      particularly effective at protecting against infectious diseases and modulating
      the immune response. It was shown that in newborns, the fecal distribution of the
      colonizing Bifidobacterium species influences the prevalence of allergic
      diseases. This study aimed to compare the faecal Bifidobacterium species of
      allergic children to those of healthy children to detect species level
      differences in faecal distribution. Stool samples were obtained from 99 children
      between 0 and 3 years of age whose clinical symptoms and laboratory reports were
      compatible with atopic dermatitis and allergic asthma. Samples were also obtained
      from 102 healthy children who were similar to the case group with respect to age
      and sex. Bifidobacteria were isolated by culture and identified at the genus
      level by API 20 A. In addition, 7 unique species-specific primers were used for
      the molecular characterization of bifidobacteria. The McNemar test was used for
      statistical analyses, and p < 0.05 was accepted as significant. Bifidobacterium
      longum was detected in 11 (11.1%) of the allergic children and in 31 (30.3%) of
      the healthy children. Statistical analysis revealed a significant difference in
      the prevalence of B. longum between these two groups (X(2): 11.2, p < 0.001).
      However, no significant differences in the prevalence of other Bifidobacterium
      species were found between faecal samples from healthy and allergic children. (p
      > 0.05). The significant difference in the isolation of B. longum from our study
      groups suggests that this species favors the host by preventing the development
      of asthma and allergic dermatitis. Based on these results, we propose that the
      production of probiotics in accordance with country-specific Bifidobacterium
      species densities would improve public health. Thus, country-specific prospective
      case-control studies that collect broad data sets are needed. 

PMID- 24878322
TI  - The interleukin-6 receptor Asp358Ala single nucleotide polymorphism rs2228145
      confers increased proteolytic conversion rates by ADAM proteases.
AB  - The pleiotropic activities of Interleukin (IL-)6 are controlled by membrane-bound
      and soluble forms of the IL-6 receptor (IL-6R) in processes called classic and
      trans-signaling, respectively. The coding single nucleotide polymorphism (SNP)
      rs2228145 of the Interleukin 6 receptor (IL-6R Asp358Ala variant) is associated
      with a 2-fold increase in soluble IL-6R (sIL-6R) serum levels resulting in
      reduced IL-6-induced C-reactive protein (CRP) production and a reduced risk for
      coronary heart disease. It was suggested that the increased sIL-6R level leads to
      decreased IL-6 classic or increased IL-6 trans-signaling. Irrespective of the
      functional outcome of increased sIL-6R serum level, it is still under debate,
      whether the increased sIL-6R serum levels emerged from differential splicing or
      ectodomain shedding. Here we show that increased proteolytic ectodomain shedding
      mediated by the A Disintegrin and metalloproteinase domain (ADAM) proteases
      ADAM10 and ADAM17 caused increased sIL-6R serum level in vitro as well as in
      healthy volunteers homozygous for the IL-6R Asp358Ala allele. Differential
      splicing of the IL-6R appears to have only a minor effect on sIL-6R level.
      Increased ectodomain shedding resulted in reduced cell-surface expression of the
      IL-6R Asp358Ala variant compared to the common IL-6R variant. In conclusion,
      increased IL-6R ectodomain shedding is a mechanistic explanation for the
      increased serum IL-6R levels found in persons homozygous for the rs2228145 IL-6R
      Asp358Ala variant. 

PMID- 24878321
TI  - The effects of constrained left versus right monocular viewing on the autonomic
      nervous system.
AB  - Asymmetrical activation of right and left hemispheres differentially influences
      the autonomic nervous system. Additionally, each hemisphere primarily receives
      retinocollicular projections from the contralateral eye. To learn if asymmetrical
      hemispheric activation induced by monocular viewing would influence relative
      pupillary size and respiratory hippus variability (RHV), a measure of
      parasympathetic activity, healthy participants had their left, right or neither
      eye patched. Pupillary sizes were then recorded with infrared pupillography.
      Pupillary dilation was significantly greater with left than right eye viewing.
      RHV, however, was not different between eye viewing conditions. These differences
      in pupil dilatation may have been caused by relatively greater activation of the
      right hemispheric-mediated sympathetic activity induced by left monocular viewing
      or relatively greater deactivation of the left hemispheric-mediated
      parasympathetic activity induced by right eye patching. The absence of an
      asymmetry in RHV, however, suggests that hemispheric asymmetry of sympathetic
      activation was primarily responsible for this ocular asymmetry of pupil dilation.

PMID- 24878323
TI  - Field-effect transistors based on few-layered alpha-MoTe(2).
AB  - Here we report the properties of field-effect transistors based on a few layers
      of chemical vapor transport grown alpha-MoTe2 crystals mechanically exfoliated
      onto SiO2. We performed field-effect and Hall mobility measurements, as well as
      Raman scattering and transmission electron microscopy. In contrast to both MoS2
      and MoSe2, our MoTe2 field-effect transistors are observed to be hole-doped,
      displaying on/off ratios surpassing 10(6) and typical subthreshold swings of ~140
      mV per decade. Both field-effect and Hall mobilities indicate maximum values
      approaching or surpassing 10 cm(2)/(V s), which are comparable to figures
      previously reported for single or bilayered MoS2 and/or for MoSe2 exfoliated onto
      SiO2 at room temperature and without the use of dielectric engineering. Raman
      scattering reveals sharp modes in agreement with previous reports, whose
      frequencies are found to display little or no dependence on the number of layers.
      Given that MoS2 is electron-doped, the stacking of MoTe2 onto MoS2 could produce
      ambipolar field-effect transistors and a gap modulation. Although the overall
      electronic performance of MoTe2 is comparable to those of MoS2 and MoSe2, the
      heavier element Te leads to a stronger spin-orbit coupling and possibly to
      concomitantly longer decoherence times for exciton valley and spin indexes. 

PMID- 24878324
TI  - Characterization of Rhodococcus equi isolates from submaxillary lymph nodes of
      wild boars (Sus scrofa), red deer (Cervus elaphus) and roe deer (Capreolus
      capreolus).
AB  - Rhodococcus equi is a soil saprophyte and an opportunistic pathogen causing
      infections in animals, and rarely in humans. The presence of R. equi in tissues
      and faeces of some wild animal species was demonstrated previously. In this study
      we characterized R. equi isolates from submaxillary lymph nodes of free-living
      wild boars (n=23), red deer (n=2) and roe deer (n=2). This is the first
      description of R. equi strains isolated from tissues of the Cervidae. All
      isolates were initially recognized as R. equi based on the phenotypic properties.
      Their identification was confirmed by matrix-assisted laser desorption/ionization
      time-of-flight mass spectrometry, detection of the choE gene and by sequence
      analysis of the 16S rRNA and rpoB genes. The presence of three plasmidic genes
      (traA, vapA and vapB) associated with R. equi virulence was investigated by PCR.
      In 16 wild boar isolates the traA and vapB genes were detected and they were
      located on virulence plasmids type 5, 7 or 11. The isolates from cervids and the
      remaining wild boar isolates were classified as avirulent based on a genotype
      traA(-)/vapA(-)B(-). In summary, these results confirm that wild boars can be a
      source of intermediately virulent R. equi strains, and indicate that red deer and
      roe deer can be a reservoir of avirulent R. equi strains. 

PMID- 24878325
TI  - Advances in vaccination against avian pathogenic Escherichia coli respiratory
      disease: potentials and limitations.
AB  - Avian pathogenic Escherichia coli (APEC) is one of the most economically
      devastating pathogens affecting the poultry industry. This group of extra
      intestinal E. coli causes a variety of clinical conditions including
      airsacculitis and cellulitis. The economic impact of APEC is mainly due to
      mortality, slower growth rates, and carcass downgrading. In commercial broiler
      operations, APEC infections are controlled indirectly by vaccination against
      other respiratory diseases and minimizing stress conditions, and directly by
      administration of antimicrobial agents to suppress the infection in already
      infected flocks. The fact that most APEC strains possess some common virulence
      factors suggests that an effective vaccine against APEC is a viable option. The
      most important virulence factors that have been investigated over the years
      include type I and P fimbriae, aerobactin iron-acquisition system, and serum
      resistance traits. Despite the potential for developing an efficacious vaccine to
      combat this economically important poultry disease, several obstacles hinder such
      efforts. Those obstacles include the cost, vaccine delivery method and timing of
      vaccination as the birds should be immune to APEC by 21 days of age. Herein, we
      review the various attempts to develop an effective vaccine against the
      respiratory form of APEC diseases in poultry. We also discuss in-depth the
      potentials and limitations of such vaccines. 

PMID- 24878327
TI  - A modified surgical technique for root coverage with an allograft: a 12-month
      randomized clinical trial.
AB  - BACKGROUND: The aim of this randomized controlled clinical study is to
      investigate whether a modified surgical technique could provide better results
      for root coverage and greater amounts of keratinized tissue (KT) with the
      acellular dermal matrix graft (ADMG). METHODS: Fifteen bilateral Miller Class I
      or II gingival recessions (GRs) were selected. The recessions were treated and
      assigned randomly to the test group (TG), and the contralateral recessions were
      assigned to the control group (CG). The ADMG was used in both groups with
      differences in the graft positioning between them. The following clinical
      parameters were measured before the surgeries and after 12 months: 1) probing
      depth; 2) relative clinical attachment level; 3) GR; 4) thickness of KT (TKT);
      and 5) KT width. A new parameter, the GR area (GRA), was measured in standardized
      photographs using a special device and software. RESULTS: There was no
      significant difference between groups in KT width and TKT parameters at the 12
      month postoperative period. However, there was a significant difference between
      the gains in GR (DeltaGR) and GRA (DeltaGRA), favoring the TG after 12 months.
      The TG presented DeltaGR = 3.04 +/- 0.29 mm and DeltaGRA= 38,919 +/- 9,238 pixel
      square values (pix(2)), and the CG presented DeltaGR= 2.61 +/- 0.41 mm and
      DeltaGRA= 22,245 +/- 9,334 pix(2) (P <0.05 and <0.001, respectively).
      CONCLUSIONS: Both techniques were successful. The TG treatment was more effective
      in reducing GR and GRA. The flap and graft position may be of importance in root
      coverage procedures outcome.

PMID- 24878326
TI  - Biased ligands at G-protein-coupled receptors: promise and progress.
AB  - Drug discovery targeting G protein-coupled receptors (GPCRs) is no longer limited
      to seeking agonists or antagonists to stimulate or block cellular responses
      associated with a particular receptor. GPCRs are now known to support a diversity
      of pharmacological profiles, a concept broadly referred to as functional
      selectivity. In particular, the concept of ligand bias, whereby a ligand
      stabilizes subsets of receptor conformations to engender novel pharmacological
      profiles, has recently gained increasing prominence. This review discusses how
      biased ligands may deliver safer, better tolerated, and more efficacious drugs,
      and highlights several biased ligands that are in clinical development. Biased
      ligands targeting the angiotensin II type 1 receptor and the MU opioid receptor
      illustrate the translation of the biased ligand concept from basic biology to
      clinical drug development. 

PMID- 24878328
TI  - Estimation of bone loss biomarkers as a diagnostic tool for peri-implantitis.
AB  - BACKGROUND: The aims of this study are to estimate the profile of bone loss
      biomarkers in peri-implant tissues and to identify potential prognostic
      biomarkers of peri-implantitis. METHODS: Peri-implant crevicular fluid samples
      collected from 164 participants (52 patients with peri-implantitis, 54 with
      mucositis, and 58 with healthy peri-implant tissues) were analyzed using enzyme
      linked immunosorbent assays to evaluate concentrations of the receptor activator
      of nuclear factor-kappaB (RANK), soluble RANK ligand (sRANKL), osteoprotegerin
      (OPG), cathepsin-K, and sclerostin. RESULTS: Concentrations of RANK, sRANKL, OPG,
      and sclerostin were significantly increased in patients with peri-implantitis
      compared with patients with healthy peri-implant tissues. Comparisons between
      peri-implantitis and mucositis demonstrated significantly higher values of
      sclerostin in peri-implantitis samples. Comparisons between mucositis and healthy
      peri-implant tissues showed significantly increased levels of RANK and cathepsin
      K in mucositis. CONCLUSION: These results are suggestive of a role of sRANKL,
      OPG, and sclerostin as prognostic biomarkers in peri-implantitis.

PMID- 24878329
TI  - Toll-like receptor 4-mediated hyper-responsiveness of gingival epithelial cells
      to lipopolysaccharide in high-glucose environments.
AB  - BACKGROUND: Increasing evidence indicates that diabetes mellitus increases the
      incidence and severity of periodontitis. Toll-like receptors (TLRs) play a role
      in the pathogenic processes of diabetes and its complications, but the effect of
      high glucose on TLRs in patients with diabetes and periodontitis is still
      unclear. METHODS: Two kinds of diabetes rat models were established. Human
      gingival epithelial cells (HGECs) were established and challenged with
      Porphyromonas gingivalis lipopolysaccharide (LPS) in the context of high glucose
      in vitro. The expressions of TLR2 and TLR4 were detected using
      immunohistochemistry, quantitative reverse transcription-polymerase chain
      reaction (qRT-PCR), and flow cytometry. The TLR4 inhibitor ethyl (6R)-6-[(2
      chloro-4-fluorophenyl)sulfamoyl]cyclohexene-1-carboxylate (TAK-242) was applied
      to block the TLR4 in HGECs, and the inflammatory factors were detected by qRT
      PCR. RESULTS: The expression of TLR2 and TLR4 in gingival tissue from both rat
      diabetes models was significantly increased compared with that of healthy
      controls. Moreover, TLR4 expression was also markedly increased in HGECs
      incubated with high glucose. The expression of interleukin (IL)-6, IL-8, and
      monocyte chemoattractant protein-1 were significantly increased in HGECs while
      challenged with LPS in the context of high glucose; however, the expression
      inflammatory cytokines were decreased significantly, whereas TLR4 was blocked by
      TAK-242. CONCLUSION: High glucose contributes to an upregulated expression of
      TLR4 in gingival epithelium, and TLR4-dependent inflammatory response may promote
      the susceptibility to periodontitis in patients with diabetes.

PMID- 24878331
TI  - Work- and travel-related physical activity and alcohol consumption: relationship
      with bone mineral density and calcaneal quantitative ultrasonometry.
AB  - A number of healthy workers rarely exercise because of a lack of time or
      resources. Physical activity related to work and everyday travel may be more
      feasible, but evidence of its beneficial effect on bone health is scarce. We
      assessed if this form of physical activity was associated with higher bone
      mineral density (BMD) and stiffness index (SI) when adjusted for recreational
      physical activity, age, body mass index, smoking, alcohol consumption, education,
      and serum level of 25-hydroxyvitamin D. Healthy workers, aged 25-54 yr, of the
      Electricity Generating Authority of Thailand were surveyed. The outcomes were BMD
      (lumbar spine, femoral neck, and total hip) and calcaneal SI. Physical activity
      was estimated using the global physical activity questionnaire and considered
      active when >600 metabolic equivalent tasks (min). Of 2268 subjects, 74% were
      men. Active male subjects had significantly higher BMD at the femoral neck and
      total hip (p<0.005). However, the association was not significant with male
      lumbar spine BMD, male SI, or any bone parameters in women (p>0.05). In men, work
      and travel physical activity seems beneficial to male bone health; hence, it
      should be encouraged. Furthermore, smoking appeared harmful while moderate
      alcohol consumption was beneficial.

PMID- 24878332
TI  - Motion produced in the unstable cervical spine by the HAINES and lateral recovery
      positions.
AB  - STUDY OBJECTIVE: To compare the amount of segmental vertebral motion produced
      with the lateral recovery position and the HAINES technique when performed on
      cadavers with destabilized cervical spines. METHODS: The cervical spines of 10
      cadavers were surgically destabilized at the C5-C6 vertebral segment. Sensors
      from an electromagnetic tracking device were affixed to the vertebrae in question
      to monitor the amount of anterior/posterior, medial/lateral, and
      distraction/compression linear motion produced during the application of the two
      study techniques. RESULTS: The statistical analysis of linear motion data did not
      reveal any significant differences between the two recovery positions.
      CONCLUSION: At this time, no single version of the recovery position can be
      endorsed for the spine-injured trauma patient. More research is needed to fully
      ascertain the safety of commonly used recovery positions.

PMID- 24878330
TI  - Prevalence and burden of headache disorders in two neighboring provinces of
      China.
AB  - To our knowledge, studies concerning the prevalence and burden of primary
      headache in China are limited to specific regions without comparison of different
      districts. A survey in a different area with similar climate and culture may
      enhance our knowledge of the factors causing primary headache and the burden of
      headache. We conducted a 1 year survey on the prevalence and burden of primary
      headache in the Chinese provinces of Guangdong and Guangxi. Our study also
      evaluated the factors behind similarities and differences affecting prevalence in
      the two regions of study. The survey methodology, which was used in an Expanded
      Program on Immunization by the World Health Organization, was adopted to
      investigate the prevalence and burden of headache patients. Random samples of 372
      local residents in Guangdong and 182 local residents in Guangxi aged 18-65 years
      were invited to a face-to-face interview. The education level and mean household
      income were higher in Guangdong (p<0.05). The 1 year prevalence of primary
      headache was 22.6% (84/372) in Guangdong and 41.2% (75/182) in Guangxi (p<0.001).
      The average financial burden of primary headache is 2.1% and 3.7% of the mean
      household income in Guangdong and Guangxi, respectively (p=0.001). The district
      with lower economic status had a higher prevalence of primary headache, and
      inevitably bears a heavier burden even with the same disease cost.

PMID- 24878333
TI  - [A 21-year-old male with trismus, septic thrombophlebitis and lung nodules].

PMID- 24878334
TI  - A fluorescence-based assay to monitor autopalmitoylation of zDHHC proteins
      applicable to high-throughput screening.
AB  - Palmitoylation, the posttranslational thioester-linked modification of a 16
      carbon saturated fatty acid onto the cysteine residue of a protein, has garnered
      considerable attention due to its implication in a multitude of disease states.
      The signature DHHC motif (Asp-His-His-Cys) identifies a family of protein
      acyltransferases (PATs) that catalyze the S-palmitoylation of target proteins via
      a two-step mechanism. In the first step, autopalmitoylation, palmitate is
      transferred from palmitoyl-CoA to the PAT, creating a palmitoyl:PAT intermediate
      and releasing reduced CoA. The palmitoyl moiety is then transferred to a protein
      substrate in the second step of the reaction. We have developed an in vitro,
      single-well, fluorescence-based enzyme assay that monitors the first step of the
      PAT reaction by coupling the production of reduced CoA to the reduction of NAD(+)
      using the alpha-ketoglutarate dehydrogenase complex. This assay is suitable for
      determining PAT kinetic parameters, elucidating lipid donor specificity and
      measuring PAT inhibition by 2-bromopalmitate. Finally, it can be used for high
      throughput screening (HTS) campaigns for modulators of protein palmitoylation. 

PMID- 24878335
TI  - Caryophyllene sesquiterpenes from the marine-derived fungus Ascotricha sp. ZJ-M-5
      by the one strain-many compounds strategy.
AB  - The marine-derived fungus Ascotricha sp. ZJ-M-5, which can produce cyclonerodiol
      analogues, a 3,4-seco lanostane triterpenoid, and diketopiperazines in an
      eutrophic medium, was subjected to a one strain-many compounds (OSMAC) analysis.
      It was found to produce three new caryophyllene derivatives (1-3) and the known
      1,3,6-trihydroxy-8-methylxanthone (4) in an oligotrophic medium, Czapek Dox broth
      with or without Mg(2+). (+)-6-O-Demethylpestalotiopsin A (1) and (+)-6-O
      demethylpestalotiopsin C (2), which have a five-membered hemiacetal structural
      moiety, showed growth inhibitory effects against HL-60 and K562 leukemia cell
      lines with the lowest GI50 value of 6.9 +/- 0.4 MUM. It can be concluded that
      modification of the culture media is still effective in the discovery of novel
      bioactive fungal secondary metabolites. 

PMID- 24878336
TI  - Health and human rights principles and standards in the provision of
      contraception.

PMID- 24878337
TI  - Theoretical study of the rate constants for the hydrogen atom abstraction
      reactions of esters with (*)OH radicals.
AB  - A systematic investigation of the rate constants for hydrogen atom abstraction
      reactions by hydroxyl radicals on esters has been performed. The geometry
      optimizations and frequency calculations were obtained using the second-order
      Moller-Plesset method with the 6-311G(d,p) basis set. The same method was also
      used in order to determine the dihedral angle potential for each individual
      hindered rotor in each reactant and transition state. Intrinsic reaction
      coordinate calculations were used in order to connect each transition state to
      the corresponding local minimum. For the reactions of methyl ethanoate with an
      (*)OH radical, the relative electronic energies were calculated using the G3 and
      the CCSD(T)/cc-pVXZ (where X = D, T, and Q) methods, which were extrapolated to
      the complete basis set (CBS) limit. The electronic energies obtained using the G3
      method were then benchmarked against the CBS results and were found to be within
      1 kcal mol(-1) of one another. The high-pressure limit rate constants for every
      reaction channel were calculated by conventional transition-state theory, with an
      asymmetric Eckart tunneling correction, using the energies obtained with the G3
      method. We report the individual, average, and total rate constants in the
      temperature range from 500 to 2200 K. Our calculated results are within a factor
      of 2 for methyl ethanoate and between 40% to 50% for methyl propanoate and methyl
      butanoate when compared to previously reported experimental data. 

PMID- 24878339
TI  - Architecture of viral genome-delivery molecular machines.
AB  - From the abyss of the ocean to the human gut, bacterial viruses (or
      bacteriophages) have colonized all ecosystems of the planet earth and evolved in
      sync with their bacterial hosts. Over 95% of bacteriophages have a tail that
      varies greatly in length and complexity. The tail complex interrupts the
      icosahedral capsid symmetry and provides both an entry for viral genome-packaging
      during replication and an exit for genome-ejection during infection. Here, we
      review recent progress in deciphering the structure, assembly and conformational
      dynamics of viral genome-delivery tail machines. We focus on the bacteriophages
      P22 and T7, two well-studied members of the Podoviridae family that use short,
      non-contractile tails to infect Gram-negative bacteria. The structure of
      specialized tail fibers and their putative role in host anchoring, cell-surface
      penetration and genome-ejection is discussed. 

PMID- 24878338
TI  - Activation of the constitutive androstane receptor inhibits gluconeogenesis
      without affecting lipogenesis or fatty acid synthesis in human hepatocytes.
AB  - OBJECTIVE: Accumulating evidence suggests that activation of mouse constitutive
      androstane receptor (mCAR) alleviates type 2 diabetes and obesity by inhibiting
      hepatic gluconeogenesis, lipogenesis, and fatty acid synthesis. However, the role
      of human (h) CAR in energy metabolism is largely unknown. The present study aims
      to investigate the effects of selective hCAR activators on hepatic energy
      metabolism in human primary hepatocytes (HPH). METHODS: Ligand-based structure
      activity models were used for virtual screening of the Specs database
      (www.specs.net) followed by biological validation in cell-based luciferase
      assays. The effects of two novel hCAR activators (UM104 and UM145) on hepatic
      energy metabolism were evaluated in HPH. RESULTS: Real-time PCR and Western
      blotting analyses reveal that activation of hCAR by UM104 and UM145 significantly
      repressed the expression of glucose-6-phosphatase and phosphoenolpyruvate
      carboxykinase, two pivotal gluconeogenic enzymes, while exerting negligible
      effects on the expression of genes associated with lipogenesis and fatty acid
      synthesis. Functional experiments show that UM104 and UM145 markedly inhibit
      hepatic synthesis of glucose but not triglycerides in HPH. In contrast,
      activation of mCAR by 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene, a selective
      mCAR activator, repressed the expression of genes associated with
      gluconeogenesis, lipogenesis, and fatty acid synthesis in mouse primary
      hepatocytes, which were consistent with previous observations in mouse model in
      vivo. CONCLUSION: Our findings uncover an important species difference between
      hCAR and mCAR in hepatic energy metabolism, where hCAR selectively inhibits
      gluconeogenesis without suppressing fatty acid synthesis. IMPLICATIONS: Such
      species selectivity should be considered when exploring CAR as a potential
      therapeutic target for metabolic disorders.

PMID- 24878342
TI  - Binding site comparison for function prediction and pharmaceutical discovery.
AB  - While structural genomics resulted in thousands of new protein crystal
      structures, we still do not know the functions of most of these proteins. One
      reason for this shortcoming is their unique sequences or folds, which leaves them
      assigned as proteins of 'unknown function'. Recent advances in and applications
      of cutting edge binding site comparison algorithms for binding site detection and
      function prediction have begun to shed light on this problem. Here, we review
      these algorithms and their use in function prediction and pharmaceutical
      discovery. Finding common binding sites in weakly related proteins may lead to
      the discovery of new protein functions and to novel ways of drug discovery. 

PMID- 24878340
TI  - Loading strategies of ring-shaped nucleic acid translocases and helicases.
AB  - Ring-shaped nucleic acid translocases and helicases catalyze the directed and
      processive movement of nucleic acid strands to support essential transactions
      such as replication, transcription, and chromosome partitioning. Assembled
      typically as hexamers, ring helicase/translocase systems use coordinated cycles
      of nucleoside triphosphate (NTP) hydrolysis to translocate extended DNA or RNA
      substrates through a central pore. Ring formation presents a topological
      challenge to the engagement of substrate oligonucleotides, and is frequently
      overcome by distinct loading strategies for shepherding specific motors onto
      their respective substrates. Recent structural studies that capture different
      loading intermediates have begun to reveal how different helicase/translocase
      rings either assemble around substrates or crack open to allow DNA or RNA strand
      entry, and how dedicated chaperones facilitate these events in some instances.
      Both prevailing mechanistic models and remaining knowledge gaps are discussed. 

PMID- 24878341
TI  - Parts, assembly and operation of the RIG-I family of motors.
AB  - Host cell invasion is monitored by a series of pattern recognition receptors
      (PRRs) that activate the innate immune machinery upon detection of a cognate
      pathogen associated molecular pattern (PAMP). The RIG-I like receptor (RLR)
      family of PRRs includes three proteins--RIG-I, MDA5, and LGP2--responsible for
      the detection of intracellular pathogenic RNA. All RLR proteins are built around
      an ATPase core homologous to those found in canonical Superfamily 2 (SF2) RNA
      helicases, which has been modified through the addition of novel accessory
      domains to recognize duplex RNA. This review focuses on the structural bases for
      pathogen-specific dsRNA binding and ATPase activation in RLRs, differential RNA
      recognition by RLR family members, and implications for other duplex RNA
      activated ATPases, such as Dicer.

PMID- 24878343
TI  - Rotary ATPases--dynamic molecular machines.
AB  - Recent work has provided the detailed overall architecture and subunit
      composition of three subtypes of rotary ATPases. Composite models of F-type, V
      type and A-type ATPases have been constructed by fitting high-resolution X-ray
      structures of individual components into electron microscopy derived envelopes of
      the intact enzymes. Electron cryo-tomography has provided new insights into the
      supra-molecular arrangement of eukaryotic ATP synthases within mitochondria. An
      inherent flexibility in rotary ATPases observed by different techniques suggests
      greater dynamics during operation than previously envisioned. The concerted
      movement of subunits within the complex might provide means of regulation and
      information transfer between distant parts of rotary ATPases thereby fine tuning
      these molecular machines to their cellular environment, while optimizing their
      efficiency. 

PMID- 24878344
TI  - The Effectiveness of Psychosocial Intervention for Individuals With Cleft Lip
      and/or Palate.
AB  - OBJECTIVE: The aim of this review was to assess the effectiveness of different
      psychological interventions for children and adults with cleft lip and/or palate
      and their parents. DESIGN: We searched six databases including MEDLINE and EMBASE
      to June 2013 and checked bibliographies. We included research that evaluated any
      psychological intervention in studies in which at least 90% of the participants
      had cleft lip and/or palate or were parents of those with cleft lip and/or
      palate. Studies containing less than 90% were excluded unless they reported
      results separately for those with cleft lip and/or palate, or raw data were
      available upon request from the authors. Inclusion assessment, data extraction,
      and risk of bias assessment were carried out independently by two reviewers.
      RESULTS: Seven studies were identified as inclusions, with only two studies being
      included in the full data analysis (one of which failed to meet the full
      inclusion criteria). The five remaining studies were included only in a narrative
      synthesis because data were available for people or parents of those with cleft
      lip and/or palate only. This highlights a distinct dearth of research into
      psychological intervention within the field of cleft lip and/or palate.
      CONCLUSIONS: The review found no evidence to support any specific intervention.
      Key uncertainties need to be identified and addressed. Adequately powered,
      methodologically rigorous randomized controlled trials are needed to provide a
      secure evidence base for psychological intervention techniques in participants
      with cleft lip and/or palate and their parents.

PMID- 24878345
TI  - Benefit of piezoosteotomy in cranioplasties for craniosynostosis correction
      versus conventional saw-and-chisel osteotomy: a pilot study.
AB  - OBJECTIVE: Pilot study evaluation of the benefit of piezoosteotomy in
      cranioplasty of craniosynostoses, based on clinical data. DESIGN: Retrospective
      case-control study. SETTING: Universitarian institution. PATIENTS:
      Craniosynostosis patients (n = 19) operated upon conventionally with a craniotome
      and microsaw versus 19 patients operated upon with a piezoosteotomy and a
      craniotome. INTERVENTION: Piezoosteotomy of the supraorbital "bandeau" and
      osteotomies on part of the parietal and occipital regions versus conventional saw
      and-chisel osteotomy. MAIN OUTCOME MEASURES: Perioperative age, weight,
      laboratory parameters, transfusion and infusion requirements, operation time, and
      blood loss. RESULTS: The intraoperative erythrocyte concentrate transfusion and
      noncolloidal infusions were comparable (P = .15; P = .56). The fresh frozen
      plasma transfusion was significantly higher (P = .03); possibly, the
      anesthesiologist's reaction was secondary to the higher irrigation-fluid
      accumulation in the aspiration bag during piezoosteotomy. The postoperative
      erythrocyte concentrate transfusion rate was significantly lower (P = .01) as a
      result of local hemostasis in piezoosteotomy. The fresh frozen plasma transfusion
      and noncolloidal infusion volumes were nonsignificantly lower (P = .27; P = .85).
      Operation time was slightly shorter with a smaller standard deviation (P = .09),
      due to a lower rate of dural lacerations and consecutive repair; patients in the
      study group were on the intensive care unit half a day less (P = .73) than those
      in the control group. C-reactive protein was significantly lower preoperatively
      (P = .00) and on the operation day (P = .01) and nonsignificant postoperatively
      (P = .81); hematocrit was postoperatively higher (P = .23). Thrombocytes were
      preoperatively lower and postoperatively higher, both nonsignificant (P = .29; P
      = .52). CONCLUSIONS: Piezoosteotomy appears to be less traumatic than
      conventional saw-and-chisel osteotomy by the evaluated parameters. The main study
      limitation is its nonrandomized retrospective design; results should be confirmed
      by a randomized controlled trial.

PMID- 24878346
TI  - Mandibular asymmetry in patients with the crouzon or apert syndrome.
AB  - The aim of this study was to describe directional and fluctuating mandibular
      asymmetry over time in children with Crouzon or Apert syndrome. Mandibular
      asymmetry of children between 7.5 and 14 years of age with Crouzon syndrome (n =
      35) and Apert syndrome (n = 24) were compared with controls (n = 327). From
      panoramic radiographs, mandibular directional and fluctuating asymmetry was
      determined for the three groups. Multilevel statistical techniques were used to
      describe mandibular asymmetry changes over time. Patients with Crouzon and Apert
      syndromes showed statistically significant more fluctuating asymmetry for
      mandibular measures than did controls. Between the Crouzon and Apert syndromes
      groups, no statistical differences were found in directional and fluctuating
      asymmetry. The control group showed statistically significantly more directional
      asymmetry than did patients with Crouzon or Apert syndrome. The controls showed
      no change over time for the directional asymmetry of condylar-ramal height;
      however, the directional asymmetry of the gonial angle increased. Patients with
      Crouzon syndrome showed side dominance for only condylar-ramal height; whereas,
      patients with Apert syndrome did not show dominance for any of the measurements.
      Apert and Crouzon syndromes showed developmental instability, in contrast to the
      controls. No statistically significant longitudinal differences were found for
      either the directional or the fluctuating asymmetry between Crouzon and Apert
      syndromes. Findings for fluctuating and directional asymmetry for both syndromes
      may indicate an inability to cope with genetic and environmental stress during
      development and treatment, compared with untreated nonsyndromic individuals.

PMID- 24878347
TI  - Does the use of particulate bone graft increase the incidence of postoperative
      infection in surgery for craniosynostosis?
AB  - OBJECTIVE: The use of particulate bone graft (PBG) has become an accepted
      technique for filling cranial defects created during cranial vault expansion for
      craniosynostosis. However, the use of PBG may be a risk factor for postoperative
      infection. The aim of this study was to compare the rate of postoperative
      infection in patients who received particulate bone graft (PBG+) with that in
      patients who did not (PBG-). DESIGN: An Institutional Review Board-approved,
      retrospective, cohort study of consecutive patients was performed. Twenty-seven
      consecutive patients in the PBG- group were compared with 21 consecutive patients
      in the PBG+ group. The two cohorts were assessed for incidence of surgical-site
      infection. RESULTS: Statistical analysis was performed using the Fisher exact
      probability test. Surgical site infection occurred in none of the PBG- patients
      (0%) versus one of the PBG+ patients (4.76%). This difference in infection rates
      between the two cohorts was not statistically significant (P = .4375).
      CONCLUSIONS: Although there may be concern that PBG could serve as a facilitative
      medium for bacterial growth, this study demonstrates no statistically significant
      increase in infection rates with its use. Particulate bone grafting of cranial
      defects resulting from cranial vault expansion in craniosynostosis remains a
      useful and valuable technique.

PMID- 24878349
TI  - Gordon syndrome: literature review and a report of two cases.
AB  - The aim of this article is to publish a literature review and report on two new
      cases of Gordon syndrome (GS), a rare syndrome documented to have an autosomal
      dominant inheritance pattern or to occur sporadically; it is characterized by
      camptodactyly, cleft palate, and talipes equinovarus. We report two exceptional
      cases of GS where both patients were also diagnosed with congenital myopathy, and
      one developed malignant hyperthermia. These are the first two cases reported
      where patients were diagnosed with both GS and congenital myopathy or where GS is
      associated with malignant hyperthermia. 

PMID- 24878348
TI  - Academic outcomes of children with isolated orofacial clefts compared with
      children without a major birth defect.
AB  - OBJECTIVE: To compare academic outcomes between children with orofacial cleft
      (OFC) and children without major birth defects. DESIGN AND SETTING: In 2007-2008,
      we mailed questionnaires to a random sample of mothers of school-aged children
      with OFC and mothers of children without major birth defects (comparison group).
      The questionnaire included Likert-scale, closed-ended, and open-ended questions
      from validated instruments. We conducted bivariate and multivariable analyses on
      parent-reported educational outcomes and bivariate analyses on parent-reported
      presence of related medical conditions between children with isolated OFC and
      unaffected children. PATIENTS/PARTICIPANTS: A random sample of 504 parents of
      children with OFCs born 1996-2002 (age 5-12 years) were identified by the North
      Carolina Birth Defects Monitoring Program. A random sample of 504 parents of
      children without birth defects born 1996-2002 was selected from North Carolina
      birth certificates. Of the 289 (28.7%) respondents, we analyzed 112 children with
      isolated OFC and 138 unaffected children. MAIN OUTCOME MEASURES: Letter grades,
      school days missed, and grade retention. RESULTS: Parents of children with
      isolated OFC reported more developmental disabilities and hearing and speech
      problems among their children than comparison parents. Children with isolated OFC
      were more likely to receive lower grades and miss more school days than
      unaffected children. Because of the low response rate, results should be
      interpreted cautiously. CONCLUSION: Children with isolated OFC may have poorer
      academic outcomes during elementary school than their unaffected peers. Future
      studies are needed to confirm these results and determine whether these
      differences persist in later grades.

PMID- 24878350
TI  - Planning your every move: the role of beta-actin and its post-transcriptional
      regulation in cell motility.
AB  - Cell motility is a tightly regulated process that involves the polymerization of
      actin subunits. The formation of actin filaments is controlled through a variety
      of protein factors that accelerate or perturb the polymerization process. As is
      the case for most biological events, cell movement is also controlled at the
      level of gene expression. Growing research explains how the beta-actin isoform of
      actin is particularly regulated through post-transcriptional events. This
      includes the discovery of multiple sites in the 3' untranslated region of beta
      actin mRNA to which RNA-binding proteins can associate. The control such proteins
      have on beta-actin expression, and as a result, cell migration, continues to
      develop, and presents a thorough process that involves guiding an mRNA out of the
      nucleus, to a specific cytosolic destination, and then controlling the
      translation and decay of this message. In this review we will provide an overview
      on the recent progress regarding the mechanisms by which actin polymerization
      modulates cell movement and invasion and we will discuss the importance of post
      transcriptional regulatory events in beta-actin mediated effects on these
      processes. 

PMID- 24878351
TI  - An introductory study of common grasps used by adults during performance of
      activities of daily living.
AB  - This paper presents the results of a descriptive survey on human grasps. Sixty
      four videos were selected to represent tasks performed in the main areas of
      activities of daily living (ADL) (personal care, meal preparation, eating,
      housekeeping, etc.). All the participants were right-handed. Elementary grasps
      were identified for each hand, and the grasp type (from a 9-type classification),
      the hands involved, and the duration were registered for each case. The results
      show that the most commonly used grasps are: pinch, non-prehensile, cylindrical,
      lateral pinch and lumbrical. The presence of these grasps in the areas of ADL is,
      however, very different (e.g., pinch is widely used in food preparation and very
      little in driving). Some grasps were used more frequently with one hand or when
      both hands were used simultaneously (e.g., special pinch was hardly used by the
      left hand). Knowing the grasp types most frequently used in ADL is essential to
      be able to assess grasp rehabilitation processes or hand prostheses development. 

PMID- 24878353
TI  - Retinoic acid induced-1 (Rai1) regulates craniofacial and brain development in
      Xenopus.
AB  - Retinoic acid induced-1 (RAI1) is an important yet understudied histone code
      reader that when mutated in humans results in Smith-Magenis syndrome (SMS), a
      neurobehavioral disorder accompanied by signature craniofacial abnormalities.
      Despite previous studies in mouse and human cell models, very little is known
      about the function of RAI1 during embryonic development. In the present study, we
      have turned to the model vertebrates Xenopus laevis and Xenopus tropicalis to
      better understand the developmental roles of Rai1. First we demonstrate that the
      Rai1 protein sequence is conserved in frogs, especially in known functional
      domains. By in situ hybridization we revealed expression of rai1 in the
      developing craniofacial tissues and the nervous system. Knockdown of Rai1 using
      antisense morpholinos resulted in defects in the developing brain and face. In
      particular, Rai1 morphants display midface hypoplasia and malformed mouth shape
      analogous to defects in humans with SMS. These craniofacial defects were
      accompanied with aberrant neural crest migration and reduction in the size of
      facial cartilage elements. Rai1 morphants also had defects in axon patterns and
      decreased forebrain ventricle size. Such brain defects correlated with a decrease
      in the neurotrophic factor, bdnf, and increased forebrain apoptosis. Our results
      emphasize a critical role of Rai1 for normal neural and craniofacial development,
      and further the current understanding of potential mechanisms that cause SMS. 

PMID- 24878354
TI  - Asymmetric growth of bilayer graphene on copper enclosures using low-pressure
      chemical vapor deposition.
AB  - In this work, we investigated the growth mechanisms of bilayer graphene on the
      outside surface of Cu enclosures at low pressures. We observed that the
      asymmetric growth environment of a Cu enclosure can yield a much higher (up to
      100%) bilayer coverage on the outside surface as compared to the bilayer growth
      on a flat Cu foil, where both sides are exposed to the same growth environment.
      By simultaneously examining the graphene films grown on both the outside and
      inside surfaces of the Cu enclosure, we find that carbon can diffuse from the
      inside surface to the outside via exposed copper regions on the inside surface.
      The kinetics of this process are examined by coupling the asymmetric growth
      between the two surfaces through a carbon diffusion model. Finally, using these
      results, we show that the coverage of bilayer graphene can be tuned simply by
      changing the thickness of the Cu foil, further confirming our model of carbon
      delivery through the Cu foil. 

PMID- 24878352
TI  - Elucidating functional heterogeneity in hematopoietic progenitor cells: a
      combined experimental and modeling approach.
AB  - A detailed understanding of the mechanisms maintaining the hierarchical balance
      of cell types in hematopoiesis will be important for the therapeutic manipulation
      of normal and leukemic cells. Mathematical modeling is expected to make an
      important contribution to this area, but the iterative development of
      increasingly accurate models will rely on repeated validation using experimental
      data of sufficient resolution to distinguish between alternative model scenarios.
      The multipotent hematopoietic progenitor FDCP-Mix cells maintain a hierarchy from
      self-renewal to post-mitotic differentiation in vitro and are accessible to
      detailed analysis. Here, we report the development of a combined mathematical
      modeling and experimental approach to study the principles underlying
      heterogeneity in FDCP-Mix cultures. We adapt a single-cell based model of
      hematopoiesis to the conditions of cell culture and describe an association
      between proliferative history and phenotype of FDCP-Mix cells. While data derived
      from population studies are incapable of distinguishing between three
      mechanistically different model scenarios, statistical analysis of single cell
      tracking data provides a resolution sufficient to select one of them. This
      scenario favors differences between granulocytic and monocytic lineage with
      respect to their proliferative behavior and death rates as a mechanistic
      explanation for the observed heterogeneity. Our results demonstrate the power of
      a combined experimental/modeling approach in which single cell fate analysis is
      the key to revealing regulatory principles at the cellular level. 

PMID- 24878355
TI  - Genomic profiling to improve embryogenesis in the pig.
AB  - Over the past decade the technology to characterize transcription during
      embryogenesis has progressed from estimating a single transcript to a reliable
      description of the entire transcriptome. Northern blots were followed by
      sequencing ESTs, quantitative real time PCR, cDNA arrays, custom oligo arrays,
      and more recently, deep sequencing. The amount of information that can be
      generated is overwhelming. The challenge now is how to glean information from
      these vast data sets that can be used to understand development and to improve
      methods for creating and culturing embryos in vitro, and for reducing
      reproductive loss. The use of ESTs permitted the identification of SPP1 as an
      oviductal component that could reduce polyspermy. Microarrays identified LDL and
      NMDA as components to replace BSA in embryo culture media. Deep sequencing
      implicated arginine, glycine, and folate as components that should be adjusted in
      our current culture system, and identified a characteristic of embryo metabolism
      that is similar to cancer and stem cells. Not only will these characterizations
      aid in improving in vitro production of embryos, but will also be useful for
      identifying, or creating conditions for donor cells that will be more likely to
      result in normal development of cloned embryos. The easily found targets have
      been identified, and now more sophisticated methods are being employed to advance
      our understanding of embryogenesis. Here the technology to study the global
      transcriptome is reviewed followed by specific examples of how the technology has
      been used to understand and improve porcine embryogenesis both in vitro and in
      vivo. 

PMID- 24878356
TI  - Effects of glyphosate-based herbicides on survival, development, growth and sex
      ratios of wood frogs (Lithobates sylvaticus) tadpoles. I: chronic laboratory
      exposures to VisionMax(r).
AB  - The purpose of this study was to determine if chronic exposure to the glyphosate
      based herbicide VisionMax((r)) affects the survival, development, growth, sex
      ratios and expression of specific genes involved in metamorphosis of wood frog
      tadpoles (Lithobates sylvaticus). We hypothesized that exposure to this herbicide
      will affect developmental rates by disrupting hormone pathways, sex ratios and/or
      gonadal morphology. Tadpoles were chronically exposed in the laboratory from
      Gosner developmental stage 25 to 42 to four different concentrations of
      VisionMax((r)) (ranging from 0.021 to 2.9 mg acid equivalents/L). Chronic
      exposures to VisionMax((r)) had direct effects on the metamorphosis of L.
      sylvaticus tadpoles by decreasing development rates, however, there was a
      decrease in survival only in the group exposed to the highest dose of
      VisionMax((r)) (2.9 mg a.e./L; from approximately 96% in the control group to 77%
      in the treatment group). There was a decrease in the number of tadpoles reaching
      metamorphic climax, from 78% in the control group to 42% in the VisionMax((r))
      (2.9 mg a.e./L) group, and a 7-day delay to reach metamorphic climax in the same
      treatment group. No effects of exposure on sex ratios or gonadal morphology were
      detected in tadpoles exposed to any of the concentrations of VisionMax((r))
      tested. Gene expression analyses in brain and tail tissues demonstrated that
      exposure to VisionMax((r)) alters the expression of key genes involved in
      development. Results showed significant interaction (two-way ANOVA, P<0.05)
      between developmental Gosner stage and treatment in brain corticotropin-releasing
      factor, deiodinase type II (dio2) and glucocorticotiroid receptor (grII) and tail
      dio2 and grII. This demonstrates that mRNA levels may be differently affected by
      treatment depending on the developmental stage at which they are assessed. At the
      same time there was a clear dose-response effect for VisionMax((r)) to increase
      thyroid hormone receptor beta in tadpole brain (F(2,69)=3.475, P=0.037) and tail
      (F(2,69)=27.569, P<0.001), regardless of developmental stage. Interestingly,
      delays in development (or survival) were only observed in the group exposed to
      2.9 mg a.e./L of VisionMax((r)), suggesting that tadpoles need to be exposed to a
      "threshold" concentration of glyphosate-based herbicide to exhibit phenotypic
      observable effects. We suggest that the upregulation of genes that trigger
      metamorphosis following VisionMax((r)) herbicide exposure might result from a
      compensatory response for the delays in development observed. Further studies are
      needed to determine if disruption of expression of these key genes leads to long
      term effects when metamorphs reach adult stages.

PMID- 24878357
TI  - Nucleic acid-based biomarkers in body fluids of patients with urologic
      malignancies.
AB  - This review focuses on the promising potential of nucleic acids in body fluids
      such as blood and urine as diagnostic, prognostic, predictive and monitoring
      biomarkers in urologic malignancies. The tremendous progress in the basic
      knowledge of molecular processes in cancer, as shown in the companion review on
      nucleic acid-based biomarkers in tissue of urologic tumors, provides a strong
      rationale for using these molecular changes as non-invasive markers in body
      fluids. The changes observed in body fluids are an integrative result, reflecting
      both tissue changes and processes occurring in the body fluids. The availability
      of sensitive methods has only recently made possible detailed studies of DNA- and
      RNA-based markers in body fluids. In addition to these biological aspects,
      methodological aspects of the determination of nucleic acids in body fluids, i.e.
      pre-analytical, analytical and post-analytical issues, are particularly
      emphasized. The characteristic changes of RNA (differential mRNA and miRNA
      expression) and DNA (concentrations, integrity index, mutations, microsatellite
      and methylation alterations) in serum/plasma and urine samples of patients
      suffering from the essential urologic cancers of the prostate, bladder, kidney
      and testis are summarized and critically discussed below. To translate the
      promising results into clinical practice, laboratory scientists and clinicians
      have to collaborate to resolve the challenges of harmonized and feasible pre
      analytical and analytical conditions for the selected markers and to validate
      these markers in well-designed and sufficiently powered multi-center studies.

PMID- 24878358
TI  - A feasible, acceptable and effective way to teach health care workers in low- and
      middle-income countries a method to manage acutely ill obstetric women.
AB  - Maternal mortality is unacceptably high in Sub Saharan Africa, which accounts for
      56% of all maternal deaths (WHO, 2012). Most maternal deaths are avoidable but
      with prompt recognition and timely intervention it is not inevitable that acute
      or critical maternal illness deteriorates to fatality (Firth and Ttendo, 2012).
      This paper discusses a project to provide multidisciplinary training in Maternal
      Acute Illness Management (M-AIM) in a low resource setting in order to actively
      address the third delay to women accessing emergency obstetric care: prompt
      receipt of effective care on reaching a medical facility. 

PMID- 24878359
TI  - Combination of 2-methoxy-3-phenylsulfonylaminobenzamide and 2-aminobenzothiazole
      to discover novel anticancer agents.
AB  - The fragment of 2-substituted-3-sulfonylaminobenzamide has been proposed to
      replace the fragment of 2-substituted-3-sulfonylaminopyridine in PI3K and mTOR
      dual inhibitors to design novel anticancer agents based on bioisostere. The
      combination of the fragment of 2-substituted-3-sulfonylaminobenzamide with the
      fragment of 2-aminobenzothiazole or 2-aminothiazolo[5,4-b]pyridine, or 2
      amino[1,2,4]triazolo[1,5-a]pyridine produced the novel structures of anticancer
      agents. As a result, nineteen target compounds were synthesized and
      characterized. Their antiproliferative activities in vitro were evaluated via MTT
      assay against four human cancer cell lines including HCT-116, A549, MCF-7 and U
      87 MG. The SAR of target compounds was preliminarily discussed. Compound 1g with
      potent antiproliferative activity was examined for its effect on the AKT and p
      AKT(473). The anticancer effect of 1g was evaluated in established nude mice HCT
      116 xenograft model. The results suggested that compound 1g can block
      PI3K/AKT/mTOR pathway and significantly inhibit tumor growth. These findings
      strongly support our assumption that the fragment of benzamide can replace the
      pyridine ring in some PI3K and mTOR dual inhibitor to design novel anticancer
      agents. 

PMID- 24878360
TI  - Carbonic anhydrase inhibitors: Synthesis, molecular docking, cytotoxic and
      inhibition of the human carbonic anhydrase isoforms I, II, IX, XII with novel
      benzenesulfonamides incorporating pyrrole, pyrrolopyrimidine and fused
      pyrrolopyrimidine moieties.
AB  - A series of novel pyrroles, pyrrolopyrimidines, pyrazolopyrrolopyrimidine,
      triazolopyrrolopyrimidines, tetrazolopyrrolopyrimidine,
      triazinopyrrolopyrimidines and pyrrolopyrimidotriazepines bearing the
      biologically active benzenesulfonamide moiety were synthesized by using pyrrole-o
      amino-carbonitrile as key intermediate. All the synthesized compounds were
      evaluated for their in vitro carbonic anhydrase (CA, EC 4.2.1.1) inhibitory
      effects against the human (h) isoforms hCA I, II, IX and XII. Among the tested
      derivatives, compounds 16, 18 and 20-24 showed potent activity as inhibitors for
      the tumor associated transmembrane isoforms (hCA IX and XII) in the nanomolar and
      subnanomolar range, with high selectivity. All compounds underwent cytotoxic
      activity assays on human breast cancer cell line (MCF-7) showing effective
      activity, comparable to that of the clinically used drug doxorubicin. 

PMID- 24878361
TI  - A novel and facile synthesis of tetra branched derivatives of nociceptin/orphanin
      FQ.
AB  - Branched peptides have been found to be useful in several research fields however
      their synthesis and purification is complicated. Here we present a novel and
      facile synthesis of tetra branched derivatives of nociceptin/orphanin FQ (N/OFQ).
      Three N/OFQ tetra branched derivatives were prepared using novel cores (PWT1,
      PWT2 and PWT3) containing a maleimido moiety. [Cys(18)]N/OFQ-NH2 was linked to
      the cores via thiol-Michael reaction characterized by high yield and purity of
      the desired final product. In the electrically stimulated mouse vas deferens PWT
      N/OFQ derivatives mimicked the inhibitory action of the natural sequence showing
      similar maximal effects and 3 fold higher potencies. The NOP selective antagonist
      SB-612111 antagonized the effects of N/OFQ and PWT derivatives with similar pKB
      values (8.02-8.48). In vivo after supraspinal administration PWT2-N/OFQ
      stimulated food intake in mice mimicking the action of N/OFQ. Compared to the
      natural peptide PWT2-N/OFQ was 40 fold more potent and elicited larger effects.
      These findings suggest that the PWT chemical strategy can be successfully applied
      to biologically active peptides to generate, with unprecedented high purity and
      yield, tetra branched derivatives displaying an in vitro pharmacological profile
      similar to that of the natural sequence associated, in vivo, to increased potency
      and effectiveness. 

PMID- 24878362
TI  - Ultrafast energy transfer in biomimetic multistrand nanorings.
AB  - We report the synthesis of LH2-like supramolecular double- and triple-stranded
      complexes based upon porphyrin nanorings. Energy transfer from the antenna dimers
      to the pi-conjugated nanoring occurs on a subpicosecond time scale, rivaling
      transfer rates in natural light-harvesting systems. The presence of a second
      nanoring acceptor doubles the transfer rate, providing strong evidence for
      multidirectional energy funneling. The behavior of these systems is particularly
      intriguing because the local nature of the interaction may allow energy transfer
      into states that are, for cyclic nanorings, symmetry-forbidden in the far field.
      These complexes are versatile synthetic models for natural light-harvesting
      systems. 

PMID- 24878363
TI  - [Application of perineum heat therapy during partum to reduce injuries that
      require post-partum stitches].
AB  - OBJECTIVE: Evaluate the effectiveness of heat, moist or dry to the perineum
      during delivery in order to reduce injuries requiring perineal suturing after
      birth, and to assess its safety in relation to the adaptation of the newborn to
      extrauterine life. METHOD: An open multicentre clinical trial directed from the
      School of Nursing at the University of Barcelona was carried out between 2009 and
      2010 in 5 Catalan Hospitals. The sample consisted of 198 pregnant women subjected
      to the natural protocol for normal delivery assistance. The pregnant women were
      randomized to three study groups: moist heat (MHG), dry heat (DHG), and control
      (CG). Usual care of the perineum was performed during labour in all groups and
      MHG or GCS was also applied in the perineum in the intervention groups. The Apgar
      score in the newborn and perineum postpartum was then assessed. Statistical tests
      were performed using a 95% confidence interval. Statistical analyses were
      performed using the SPSS version 17. RESULTS: Perinea that required no suturing:
      MHG 71% (47) versus CG 56% (37), OR: 1.803; (95% CI: 0.881-3.687); DHG 62% (41)
      versus CG 56% (37), OR:1.285 (95% CI: 0.641-2.577); MHG 71% (47) versus DHG 62%
      (41), OR:1.402 (95% CI: 0.680-2.890). MEAN: Apgar score 5', MHG: 9.91; DHG: 9.98,
      CG: 9.98. p=0.431. CONCLUSIONS: The application of heat therapy to the perineum
      during labour did not significantly reduce perineal suturing after birth.
      However, better perineal results were observed with moist heat. Heat therapy does
      not alter neonatal outcomes measured by Apgar score.

PMID- 24878364
TI  - Housing First is associated with reduced use of emergency medical services.
AB  - OBJECTIVE: Chronically homeless adults with severe alcohol problems are
      disproportionately burdened with health-care problems and are high utilizers of
      emergency medical services (EMS). Single-site Housing First (HF), which provides
      immediate, permanent, low-barrier, nonabstinence-based, supportive housing, has
      been associated with reduced publicly funded service utilization. The aims of the
      current study were to determine whether time spent in single-site HF predicted
      decreases in EMS contacts 2 years subsequent to single-site HF move-in, and to
      describe medical conditions and injuries associated with EMS contacts in a sample
      of chronically homeless individuals with severe alcohol problems. METHODS:
      Participants were 91 chronically homeless adults with severe alcohol problems who
      were enrolled in a single-site HF program between December 2005 and March 2007 in
      Seattle, Washington. We obtained administrative data on exposure to HF and EMS
      utilization for the 2 years prior to and the 2 years subsequent to participants'
      move-in date. EMS utilization variables included patient type (i.e., primary
      presenting problem), trauma/injury mechanism (i.e., EMS classification of the
      cause of the trauma or injury), level of care (i.e., basic life support, advanced
      life support), and transport destination. RESULTS: After controlling for baseline
      EMS contacts, participants evinced 3% fewer EMS contacts for each additional
      month of single-site HF exposure. From the baseline to follow-up period, the mean
      number of EMS contacts declined from 15.85 (SD = 22.96) to 9.54 (SD = 15.08),
      representing a 54% reduction in the number of EMS contacts. Most calls were
      responded to by EMTs providing basic life support, and the majority resulted in
      transport to a local level I trauma center. The most common presenting
      difficulties were medical illness and trauma. Substance use and psychiatric
      difficulties were infrequently documented as the primary problem. CONCLUSIONS:
      Our findings support recent assertions that housing is health care and indicate
      that the amount of time spent in single-site HF is associated with significant
      reductions in EMS utilization for at least 2 years subsequent to move-in. These
      findings also underscore the high levels of medical illness and trauma exposure
      among chronically homeless adults with severe alcohol problems.

PMID- 24878368
TI  - Electronic and vibrational properties of stable isomers of (SiO)n((0,+/-)) (n = 2
      7) clusters.
AB  - First-principles calculations based on density functional theory have been
      performed to explore the stable configurations, electronic structures, and
      vibrational spectra of neutral and charged silicon monoxide clusters (SiO)n((0,+/
      )) (n = 2-7), which could be used as precursors in the synthesis of silicon
      nanowires. Our theoretical calculations provide new results on characteristic
      electron affinity, ionization potential, and vibrational spectroscopy, guiding
      future experiments in the synthesis of high-quality silicon nanowires.
      Specifically, as the number of SiO units n increases, IR spectra of (SiO)n(+/-)
      and Raman spectra of (SiO)n(-) show an evident blue shift, and Raman spectra of
      (SiO)n demonstrate a red shift. Moreover, most of the neutral silicon monoxide
      clusters have strong IR intensities and weak Raman activities, while most of the
      anionic counterparts have relatively weak IR intensities and strong Raman
      activities. Some other energetically competitive isomers of some (SiO)n((0,+/-))
      species were also studied for comparison. 

PMID- 24878365
TI  - Chemogeography and antimicrobial activity of essential oils from Geijera
      parviflora and Geijera salicifolia (Rutaceae): two traditional Australian
      medicinal plants.
AB  - Essential oils were hydrodistilled from 27 specimens of Geijera parviflora
      Lindl., (Rutaceae) and nine specimens of Geijera salicifolia Schott, collected
      over a wide geographic range in New South Wales, Queensland and South Australia.
      Essential oils were produced by traditional hydrodistillation and characterised
      using GC-MS. From one specimen a serendipitous discovery was made of bioactive
      coumarins dissolved in the hydrosol, which were the coumarins isopsoralen,
      xanthyletine and osthole. These coumarins were not present in the essential oil
      from that specimen. Using essential oil composition from all specimens, principal
      component analysis (PCA) demonstrated nine clusters for G. parviflora and three
      for G. salicifolia. Some clusters are representative of previously described
      chemotypes and some are reflective of possible chemotypes requiring more
      comprehensive sampling for confirmation. Thus, another three or four possible
      chemotypes of G. parviflora and one of G. salicifolia have been tentatively
      identified. Using micro-titre plate broth dilution assays, antibacterial and
      antifungal activity of all chemotypes was investigated. In this regard, the
      'green oil' chemotype, restricted to G. parviflora, with major components
      linalool, geijerene/pregeijerene, 1,8-cineol and bicyclogermacrene, demonstrated
      the highest antimicrobial and free radical scavenging activity. Thus, in the
      light of traditional use reports of local analgaesia and bioactivity demonstrated
      in the current study, oils from select chemotypes of G. parviflora may be useful
      in suitably compounded lotions and creams designed for topical antimicrobial
      applications and local pain relief. In addition, because major components are
      known for insecticidal activities, such lotions may also be useful as topically
      applied insect repellents. 

PMID- 24878366
TI  - Ammonia-induced energy disorders interfere with bilirubin metabolism in
      hepatocytes.
AB  - Hyperammonemia and jaundice are the most common clinical symptoms of hepatic
      failure. Decreasing the level of ammonia in the blood is often accompanied by a
      reduction in bilirubin in patients with hepatic failure. Previous studies have
      shown that hyperammonemia can cause bilirubin metabolism disorders, however it is
      unclear exactly how hyperammonemia interferes with bilirubin metabolism in
      hepatocytes. The purpose of the current study was to determine the mechanism or
      mechanisms by which hyperammonemia interferes with bilirubin metabolism in
      hepatocytes. Cell viability and apoptosis were analyzed in primary hepatocytes
      that had been exposed to ammonium chloride. Mitochondrial morphology and
      permeability were observed and analyzed, intermediates of the tricarboxylic acid
      (TCA) cycle were determined and changes in the expression of enzymes related to
      bilirubin metabolism were analyzed after ammonia exposure. Hyperammonemia
      inhibited cell growth, induced apoptosis, damaged the mitochondria and hindered
      the TCA cycle in hepatocytes. This led to a reduction in energy synthesis,
      eventually affecting the expression of enzymes related to bilirubin metabolism,
      which then caused further problems with bilirubin metabolism. These effects were
      significant, but could be reversed with the addition of adenosine triphosphate
      (ATP). This study demonstrates that ammonia can cause problems with bilirubin
      metabolism by interfering with energy synthesis. 

PMID- 24878367
TI  - Improved life satisfaction and pain reduction: follow-up of a 5-week
      multidisciplinary long-term pain rehabilitation programme.
AB  - BACKGROUND: Multidisciplinary rehabilitation programmes can improve physical
      functioning and help patients with long-term pain back to work. Little is known,
      however, of the extent to which such rehabilitation also affects life
      satisfaction, pain severity, and disability. We wanted to evaluate if a 5-week
      rehabilitation programme for patients with long-term pain improves life
      satisfaction and decreases pain severity and disability. METHODS: The subjects
      were 164 patients aged 18-65 years from a pain rehabilitation clinic. Most of
      them were referred from primary care units. One group of repeated tests was used.
      Participants were asked to fill out the LiSat-11 checklist and parts of the
      Multidimensional Pain Inventory (MPI), including pain severity, at admission, at
      discharge, and 1 year after the rehabilitation programme. RESULTS: Satisfaction
      with life as a whole, and six of ten LiSat-11 domains improved during the follow
      up, though none reached the levels for the general population. MPI subscales pain
      severity, pain interference, life control, and affective distress improved,
      whereas no change was observed for general activity. Patients older than 38 years
      decreased more in MPI affective distress than younger patients. Gender, pain
      severity, and work status before the programme did not significantly influence
      the outcome. CONCLUSIONS: The results indicate that multidisciplinary
      rehabilitation improves life satisfaction, reduces pain severity, and reduces
      negative psychological, social, and behavioural effects of pain. These outcome
      variables relate to domains known to be of interest for patients and should
      therefore be considered for evaluation of rehabilitation programmes for long-term
      pain.

PMID- 24878369
TI  - Population genetic structure and trait associations in forest savory using
      molecular, morphological and phytochemical markers.
AB  - In this investigation, morphological, phytochemical and ISSR markers were used to
      estimate the relationships among and within seven populations of white savory
      (Satureja mutica), belonging to four provinces in Iran. The individuals were
      phenotypically diverse, which stamen length, corolla length, corolla diameter,
      calyx length, bract length, inflorescence length, calyx length and bracteole
      width were characteristics with the highest variation. Leaf dimensions were in
      significant correlation with flower and inflorescence characteristics. Chemical
      compounds of essential oils were found variable in various individuals and all
      samples were principally composed of phenolic constituents (carvacrol and/or
      thymol). As a consequence, the plants were classified into two major chemotypes
      including carvacrol and thymol. A total of 197 band positions were produced by 14
      ISSR primers, of which 176 were found polymorphic with 88.91% polymorphism. ISSR
      genetic similarity values among individuals ranged between 0.45 and 0.94 which
      was indicative of a high level of genetic variation. Multiple regression analysis
      (MRA) revealed that phytochemical compositions as dependent variable, showed
      statistically significant correlation and in association with leaf and flower
      traits as independent variable, indicating a main role of leaf and flower on
      production of these compounds. Also, several ISSR fragments were found associated
      with some morphological traits and phytochemical compositions. The high diversity
      within and among populations of S. mutica according to different data systems
      could provide useful information for conservation and selection of cross-parents
      in breeding programs. 

PMID- 24878370
TI  - Combined deletion of DAZ2 and DAZ4 copies of Y chromosome DAZ gene is associated
      with male infertility in Tunisian men.
AB  - The relationship between male infertility and AZFc micro-deletions that remove
      multiple genes of the Y chromosome varies among countries and populations. The
      purpose of this study was to analyze the prevalence and the characteristics of
      different Deleted in azoospermia (DAZ) gene copy deletions and their association
      with spermatogenic failure and male infertility in Tunisian men. 241 infertile
      men (30.7% azoospermic (n=74), 31.5% oligozoospermic (n=76) and 37.7%
      normozoospermic (n=91)) and 115 fertile healthy males who fathered at least one
      child were included in the study. Three DAZ-specific single nucleotide variant
      loci and six bi-allelic DAZ-SNVs (I-VI) were analyzed using polymerase chain
      reaction (PCR)-restriction fragment length polymorphism and PCR. Our findings
      showed high frequencies of infertile men (73.85%) and controls (78.26%) having
      only three DAZ gene copies (DAZ1/DAZ2/DAZ3 or DAZ1/DAZ3/DAZ4 variants); so
      deletion of DAZ2 or DAZ4 were frequent both in infertile (36.5% and 37.3%,
      respectively) and fertile groups (33.9% and 44.3%, respectively) and removing
      DAZ4 copy was significantly more frequent in oligospermic than in normospermic
      men (p=0.04) in infertile group. We also report for the first time that
      simultaneous deletion of both DAZ2 and DAZ4 copies was significantly more common
      in infertile men (12.4%) than in fertile men (4.3%) (p=0.01). However, deletions
      of DAZ1/DAZ2 and DAZ3/DAZ4 clusters were very rare. Analysis of DAZ gene copies
      in Tunisian population, suggested that the simultaneous deletion of DAZ2 and DAZ4
      gene copies is associated with male infertility, and that oligospermia seems to
      be promoted by removing DAZ4 copy. 

PMID- 24878371
TI  - Innovative immunization protocols using chimeric recombinant protein for the
      production of polyspecific loxoscelic antivenom in horses.
AB  - A chimeric protein (rCpLi) was constructed expressing three epitopes of rLiD1, a
      dermonecrotic toxin from the venom of Loxosceles intermedia spider. We have
      analyzed the neutralization potential of sera obtained by immunization of horses
      with rCpLi and rCpLi combined with initial doses of venoms and compared these
      with antivenom traditionally produced in horses using crude Loxosceles gaucho,
      Loxosceles laeta and L. intermedia venoms as antigens. We have demonstrated by
      ELISA that horses immunized with three initial doses of crude venom containing
      mixtures of L. intermedia, L. gaucho and L. laeta followed by nine doses of rCpLi
      generate antibodies with the same reactivity as those produced following
      immunization with traditional antivenom, towards the venoms of the three
      Loxosceles sp. species. Results from in vivo and in vitro neutralization assays
      showed that the new horse sera are able to neutralize the dermonecrotic activity
      of Loxosceles venoms, which are of medical importance in Brazil and some of these
      sera are capable of meeting the necessary potency requirements that could allow
      for their therapeutic use in humans. This immunization strategy combining both
      antigens used approximately 67% less crude Loxosceles venoms compared to
      traditional immunization protocol and can mean the development of Loxosceles
      antivenoms with the consequent reduction of devastation of arachnid fauna.

PMID- 24878372
TI  - Neutralisation of the pharmacological activities of Bothrops alternatus venom by
      anti-PLA2 IgGs.
AB  - Basic phospholipases A2 (PLA2) are toxic and induce a wide spectrum of
      pharmacological effects, although the acidic enzyme types are not lethal or cause
      low lethality. Therefore, it is challenging to elucidate the mechanism of action
      of acidic phospholipases. This study used the acidic non-toxic Ba SpII RP4 PLA2
      from Bothrops alternatus as an antigen to develop anti-PLA2 IgG antibodies in
      rabbits and used in vivo assays to examine the changes in crude venom when pre
      incubated with these antibodies. Using Ouchterlony and western blot analyses on
      B. alternatus venom, we examined the specificity and sensitivity of phospholipase
      A2 recognition by the specific antibodies (anti-PLA2 IgG). Neutralisation assays
      using a non-toxic PLA2 antigen revealed unexpected results. The (indirect)
      haemolytic activity of whole venom was completely inhibited, and all
      catalytically active phospholipases A2 were blocked. Myotoxicity and lethality
      were reduced when the crude venom was pre-incubated with anti-PLA2
      immunoglobulins. CK levels in the skeletal muscle were significantly reduced at 6
      h, and the muscular damage was more significant at this time-point compared to 3
      and 12 h. When four times the LD50 was used (224 MUg), half the animals treated
      with the venom-anti PLA2 IgG mixture survived after 48 h. All assays performed
      with the specific antibodies revealed that Ba SpII RP4 PLA2 had a synergistic
      effect on whole-venom toxicity. IgG antibodies against the venom of the
      Argentinean species B. alternatus represent a valuable tool for elucidation of
      the roles of acidic PLA2 that appear to have purely digestive roles and for
      further studies on immunotherapy and snake envenoming in affected areas in
      Argentina and Brazil.

PMID- 24878373
TI  - Ciguatera fish poisoning in Hong Kong--a 10-year perspective on the class of
      ciguatoxins.
AB  - The present study used liquid chromatography-tandem mass spectrometry (LC-MS/MS)
      to investigate retrospectively ciguatoxin (CTX)-positive samples as determined by
      mouse bioassay (MBA) in the past 10 years in Hong Kong. The results showed that
      Pacific CTXs (P-CTX-1, -2 and -3) were the most commonly observed toxins found in
      the samples, indicating Pacific Ocean areas as the most important origin of
      ciguatera fish poisoning. Clinical diagnosis from ciguatera patients also
      revealed the predominance of neurological illnesses in most cases, supporting
      intoxication of Pacific origin. This study demonstrated the ability of laboratory
      analysis to identify and quantify Pacific CTXs in suspected fish samples, so as
      to support the clinical diagnosis of ciguatera. Comparative analysis (Student's t
      test and Spearman's rank correlation analysis) on the two CTX detection methods
      showed approximate linearity for overall P-CTXs (P-CTX-1, -2 and -3)/P-CTX-1
      alone as derived by LC-MS/MS and total toxicity levels (P-CTX-1 equivalent) as
      determined by MBA. The LC-MS/MS method coupled with the rapid extraction method
      could allow the detection of trace amount of CTXs at levels below the clinically
      relevant limit, 0.1 ppb P-CTX-1 in fish flesh. For practical application, the
      adoption of a two-tiered approach for testing, chemical analysis by LC-MS/MS for
      toxic fish screening, coupled with biological assay by MBA for final toxicity
      confirmation, was proposed for first-line screening of CTX in potentially
      contaminated fish samples in the market, with an aim to minimizing the use of
      laboratory mice and at the same time providing reasonably effective means for
      routine analysis.

PMID- 24878374
TI  - Margatoxin is a non-selective inhibitor of human Kv1.3 K+ channels.
AB  - Margatoxin (MgTx), an alpha-KTx scorpion toxin, is considered a selective
      inhibitor of the Kv1.3K + channel. This peptide is widely used in ion channel
      research; however, a comprehensive study of its selectivity with
      electrophysiological methods has not been published yet. The lack of selectivity
      might lead to undesired side effects upon therapeutic application or may lead to
      incorrect conclusion regarding the role of a particular ion channel in a
      physiological or pathophysiological response either in vitro or in vivo. Using
      the patch-clamp technique we characterized the selectivity profile of MgTx using
      L929 cells expressing mKv1.1 channels, human peripheral lymphocytes expressing
      Kv1.3 channels and transiently transfected tsA201 cells expressing hKv1.1,
      hKv1.2, hKv1.3, hKv1.4-IR, hKv1.5, hKv1.6, hKv1.7, rKv2.1, Shaker-IR, hERG,
      hKCa1.1, hKCa3.1 and hNav1.5 channels. MgTx is indeed a high affinity inhibitor
      of Kv1.3 (Kd = 11.7 pM) but is not selective, it inhibits the Kv1.2 channel with
      similar affinity (Kd = 6.4 pM) and Kv1.1 in the nanomolar range (Kd = 4.2 nM).
      Based on our comprehensive data MgTX has to be considered a non-selective Kv1.3
      inhibitor, and thus, experiments aiming at elucidating the significance of Kv1.3
      in in vitro or in vivo physiological responses have to be carefully evaluated. 

PMID- 24878375
TI  - Unraveling snake venom complexity with 'omics' approaches: challenges and
      perspectives.
AB  - The study of snake venom proteomes (venomics) has been experiencing a burst of
      reports, however the comprehensive knowledge of the dynamic range of proteins
      present within a single venom, the set of post-translational modifications (PTMs)
      as well as the lack of a comprehensive database related to venom proteins are
      among the main challenges in venomics research. The phenotypic plasticity in
      snake venom proteomes together with their inherent toxin proteoform diversity,
      points out to the use of integrative analysis in order to better understand their
      actual complexity. In this regard, such a systems venomics task should encompass
      the integration of data from transcriptomic and proteomic studies (specially the
      venom gland proteome), the identification of biological PTMs, and the estimation
      of artifactual proteomes and peptidomes generated by sample handling procedures. 

PMID- 24878377
TI  - In memoriam: Professor David John Hugh Cockayne FRS, 1942-2010: editorial
      introducing the special issue of MICRON in tribute to David Cockayne.

PMID- 24878376
TI  - Environmental modulation of microcystin and beta-N-methylamino-L-alanine as a
      function of nitrogen availability.
AB  - The most significant modulators of the cyanotoxins microcystin and beta-N
      methylamino-L-alanine in laboratory cyanobacterial cultures are the concentration
      of growth-medium combined nitrogen and nitrogen uptake rate. The lack of field
      studies that support these observations led us to investigate the cellular
      content of these cyanotoxins in cyanobacterial bloom material isolated from a
      freshwater impoundment and to compare these to the combined nitrogen
      availability. We established that these toxins typically occur in an inverse
      relationship in nature and that their presence is mainly dependent on the
      environmental combined nitrogen concentration, with cellular microcystin present
      at exogenous combined nitrogen concentrations of 29 MUM and higher and cellular
      BMAA correlating negatively with exogenous nitrogen at concentrations below 40
      MUM. Furthermore, opposing nutrient and light gradients that form in dense
      cyanobacterial blooms may result in both microcystin and BMAA being present at a
      single sampling site.

PMID- 24878378
TI  - Polymeric micelles for pH-responsive delivery of cisplatin.
AB  - Methoxy poly(ethylene oxide)-block-poly-(alpha-carboxylate-epsilon-caprolactone)
      (PEO-b-PCCL) was used to develop pH-responsive polymeric micelles for the
      delivery of cisplatin (CDDP). Micelles were prepared through complexation of CDDP
      with the pendant carboxyl groups on the poly(epsilon-caprolactone) core, perhaps
      through coordinate bonding. The obtained micelles were characterized using
      dynamic light scattering (DLS) measurement for size and stability. The in vitro
      release of CDDP at different pHs (7.4, 6.0 and 5.0) was evaluated. The in vitro
      cell uptake as well as cytotoxicity of developed micelles against two breast
      cancer cell lines, i.e. MDA-MB-435 and MDA-MB-231, were also assessed and
      compared to free CDDP as control. DLS results showed PEO-b-PCCL to form stable
      micelles with an average diameter of <50 nm upon complexation with CDDP.
      Developed polymeric micelles were capable of slowly releasing CDDP in
      physiological pH. However, CDDP release from polymeric micelles was triggered
      upon exposure to electrolytes and/or acidic pHs mimicking that of extracellular
      tumor microenvironment or intracellular organelles. Consistent with the slow
      release of CDDP from its polymeric micellar formulation, polymeric micellar CDDP
      exhibited lower cytotoxicity and CDDP intracellular uptake compared to free drug.
      The results indicate a great potential for the developed formulation in platinum
      therapy of breast cancer.

PMID- 24878379
TI  - Serum influence on in-vitro gene delivery using microbubble-assisted ultrasound.
AB  - BACKGROUND: Plasmid DNA (pDNA) is attractive molecule for gene therapy. pDNA
      targeted delivery by efficient and safe methods is required to enhance its intra
      tissue bioavailability. Among non-viral methods, sonoporation has become a
      promising method for in-vitro and in-vivo pDNA delivery. The efficiency of non
      viral delivery methods of pDNA is generally limited by the presence of serum.
      PURPOSE: The aim of this study was to evaluate the influence of serum on in-vitro
      pDNA delivery using microbubble-assisted ultrasound. METHODS: The effects of a
      range of serum concentrations (0-50%) on efficiency of in-vitro pDNA delivery by
      sonoporation were determined on human glioblastoma cells. Furthermore, the
      influence of the serum on cell viability, membrane permeabilization, microbubble
      destruction, and pDNA topology were also assessed. RESULTS: In-vitro results
      showed that a low serum concentration (i.e. <=1%) induced a significant increase
      in transfection level through an increase in cell viability. However, a high
      serum concentration (i.e. >=5%) resulted in a significant decrease in cell
      transfection, which was not associated with a decrease in membrane
      permeabilization or loss in cell viability. This decrease in transfection level
      was in fact positively correlated to changes in pDNA topology. CONCLUSION: Serum
      influences the efficiency of in-vitro pDNA delivery by sonoporation through
      change in pDNA topology.

PMID- 24878382
TI  - The antihypertensive effects of sodium nitrite are not associated with
      circulating angiotensin converting enzyme inhibition.
AB  - Nitrite-derived nitric oxide (NO) formation exerts antihypertensive effects.
      Because NO inhibits angiotensin converting enzyme (ACE) activity, we carried a
      comprehensive series of experiments in rats to test the hypothesis that sodium
      nitrite exerts antihypertensive effects by inhibiting ACE. We examined whether
      sodium nitrite (15 mg/kg; or vehicle; by gavage): (I) attenuates the pressor
      responses to angiotensin I at doses of 0.03, 0.1, 0.3, 1, 3, and 10 MUg/kg
      intravenously; (II) attenuates the acute hypertension induced by L-NAME (100
      mg/kg; or vehicle; by gavage); (III) attenuates the chronic hypertension induced
      by L-NAME (1 g/L in drinking water; or vehicle) administered for 6 weeks; (IV)
      attenuates the hypertension in the 2 kidney-1 clip (2K1C) chronic hypertension
      model. Blood samples were collected at the end of each study and plasma
      angiotensin converting enzyme (ACE) activity was measured with a fluorimetric
      assay using Hippuryl-His-Leu as substrate. ACE inhibitors were used as positive
      controls. Plasma nitrite concentrations were measured by ozone-based reductive
      chemiluminescence. The in vitro effects of sodium nitrite (0, 1, 3, 10, 30, 100
      MUmol/L) on plasma ACE activity were also determined. We found that sodium
      nitrite did not affect the pressor responses to angiotensin I. Moreover, while
      sodium nitrite exerted significant antihypertensive effects in acute and chronic
      hypertension models, no significant effects on plasma ACE activity were found. In
      vitro experiments showed no effects of sodium nitrite on plasma ACE activity.
      This is the first study to demonstrate that the acute and chronic
      antihypertensive effects of sodium nitrite are not associated with significant
      inhibition of circulating ACE activity.

PMID- 24878380
TI  - Association of recent exposure to ambient metals on fractional exhaled nitric
      oxide in 9-11 year old inner-city children.
AB  - Exposure to ambient metals in urban environments has been associated with wheeze,
      and emergency room visits and hospitalizations due to respiratory illness.
      However, the effect of ambient metals exposure on airway inflammation, and how
      these associations may be modified by seroatopy, has not been determined.
      Fractional exhaled nitric oxide (FENO) is a reliable proxy marker of airway
      inflammation. We hypothesized that recent ambient concentrations of Ni, V, Zn and
      Fe would be associated differentially with proximal and distal fractions of
      exhaled NO, and that these associations would be modified by seroatopy. As part
      of the Columbia Center for Children's Environmental Health (CCCEH) birth cohort
      study, 9-11 year old children (n=192) were evaluated. Ambient measures of Ni, V,
      Zn and Fe were obtained from a local central monitoring site and averaged over 9
      days based on three 24h measures every third day. Fractional exhaled nitric oxide
      (FENO) samples were obtained at constant flows of 50 (FENO50), 83 and 100mL/s,
      and used to determine surrogate measures for proximal (JNO) and alveolar (Calv)
      inflammation. Seroatopy was determined by specific IgE at age 7. Data were
      analyzed using multivariable linear regression. Ambient V and Fe concentrations
      were associated positively with FENO50 (p=0.018, p=0.027). Ambient Fe was
      associated positively with JNO (p=0.017). Ambient Ni and V concentrations were
      associated positively with Calv (p=0.004, p=0.018, respectively). A stronger
      association of Ni concentrations with Calv was observed among the children with
      seroatopy. These results suggest that ambient metals are associated
      differentially with different fractions of FENO production, and this relationship
      may be modified by seroatopy.

PMID- 24878383
TI  - Vertebral body segmentation with prior shape constraints for accurate BMD
      measurements.
AB  - We propose a novel vertebral body segmentation approach, which is based on the
      graph cuts technique with shape constraints. The proposed approach depends on
      both image appearance and shape information. Shape information is gathered from a
      set of training shapes. Then we estimate the shape variations using a new
      distance probabilistic model which approximates the marginal densities of the
      vertebral body and its background in the variability region using a Poisson
      distribution refined by positive and negative Gaussian components. To segment a
      vertebral body, we align its 3D shape with the training 3D shape so we can use
      the distance probabilistic model. Then its gray level is approximated with a
      Linear Combination of Gaussians (LCG) with sign-alternate components. The spatial
      interaction between the neighboring voxels is identified using a new analytical
      approach. Finally, we formulate an energy function using both appearance models
      and shape constraints. This function is globally minimized using s/t graph cuts
      to get the optimal segmentation. Experimental results show that the proposed
      technique gives promising results compared to other alternatives. Applications on
      Bone Mineral Density (BMD) measurements of vertebral body are given to illustrate
      the accuracy of the proposed segmentation approach. 

PMID- 24878381
TI  - Adenosine, a hepato-protective component in active hexose correlated compound:
      its identification and iNOS suppression mechanism.
AB  - Supplementation of active hexose correlated compound (AHCC) improved the
      prognosis of postoperative hepatocellular carcinoma patients. Excess production
      of nitric oxide (NO) by inducible NO synthase (iNOS) is an inflammatory biomarker
      in liver injury. AHCC suppressed iNOS induction in hepatocytes, suggesting that
      AHCC has a potential liver-protective effect. However, the active component in
      AHCC responsible for NO suppressive activities has not been identified. The
      objective of this study was to identify this NO suppressive component and to
      investigate its mechanisms of action. AHCC was subjected to fractionation by
      cation exchanger, size exclusion chromatography, and normal- and reversed-phase
      HPLC. Aliquots of the fractions were added to primary cultured rat hepatocytes
      stimulated with interleukin (IL)-1beta, and NO production was assayed. By
      activity-guided fractionation and electron spray ionization mass spectrometry
      analysis, adenosine was identified as one of the NO suppressive components in
      AHCC. Adenosine inhibited NO production, and reduced the expression of iNOS
      protein and mRNA. It had no effects on IkappaB degradation, but it inhibited NF
      kappaB activation. Adenosine also inhibited the upregulation of type I IL-1
      receptor (IL-1RI). Experiments with iNOS promoter-luciferase constructs revealed
      that adenosine decreased the levels of iNOS mRNA at the promoter transactivation
      and mRNA stabilization steps. Adenosine decreased the expression of the iNOS gene
      antisense transcript, which is involved in iNOS mRNA stability. Adenosine in AHCC
      suppressed iNOS induction by blocking NF-kappaB activation and the upregulation
      of the IL-1RI pathways, resulting in the inhibition of NO production. 

PMID- 24878385
TI  - Experimental pain in the gingiva and its impact on prefrontal cortical
      hemodynamics: a functional near-infrared spectroscopy study.
AB  - Evaluating alterations in brain activity in response to pain stimulus can help
      understand the mechanisms underlying pain perception. We measured oxygenated
      hemoglobin (oxy-Hb) levels using functional near-infrared spectroscopy (fNIRS) in
      order to assess prefrontal cortex activation after inducing a pain stimulus to
      the gingiva. Twenty-three right-handed, healthy male subjects (mean age: 29.3+/
      3.6 years) were subjected to a mild pain stimulus to the tissue around the right
      maxillary central incisor. The periodontal pain stimulus (PPS) was elicited from
      a pocket probe, and a multi-channel fNIRS system with its accompanying 22-channel
      probes was used for measuring oxy-Hb levels. Mean oxy-Hb levels for each channel
      were calculated on the basis of values obtained at rest and during the PPS load,
      for 1min each. The change in oxy-Hb level was calculated by subtracting oxy-Hb at
      rest from oxy-Hb levels during PPS load. Oxy-Hb levels in each channel during
      both conditions were then compared using the paired t-test and Bonferroni
      correction. Pain stimulation caused oxy-Hb levels to decrease in virtually all
      areas of the prefrontal cortex, particularly, in the superior frontal gyrus, the
      middle frontal gyrus, and the orbital part of the superior, middle, and inferior
      frontal gyrus, on the brain side contralateral to the pain load. This measurement
      could prove beneficial as an index for objective pain evaluation. 

PMID- 24878384
TI  - New mutations and polymorphisms of the ATP7B gene in sporadic Wilson disease.
AB  - Wilson's disease (WD) is a rare autosomal recessive genetic disorder of copper
      metabolism resulting in brain damage, liver failure, and neurological impairment
      and psychiatric disturbances, as a result of excessive copper accumulation in the
      brain, liver, kidneys and eyes. ATP7B, encoding a copper transporter P-ATPase was
      identified as the causative gene of WD. Mutations in the ATP7B gene lead to the
      defection of the transmembrane transporter so that it can not metabolize copper
      effectively. We reported the clinical and molecular features of three unrelated
      and non-consanguineous WD patients. We performed molecular genetic analysis of
      the ATP7B gene in all cases by DNA sequencing, and revealed 7 novel single
      nucleotide polymorphisms (SNPs) and 8 well known mutations. Among them, that
      novel SNP (c. -520 C>T) and two well known mutations (c. 2310 C>G/p. Leu700Leu,
      c. 2333 G>T/A/p. Arg778Leu/Gln) coexisted in all patients and they were
      heterozygous and homozygous in the youngest case, respectively, indicating that
      they may be correlated to the pathogenesis and potentially used as a genetic
      biomarker for early WD diagnosis. 

PMID- 24878386
TI  - Preparation and characterization of co-amorphous Ritonavir-Indomethacin systems
      by solvent evaporation technique: improved dissolution behavior and physical
      stability without evidence of intermolecular interactions.
AB  - The aim of this study was to stabilize the amorphous form of Ritonavir (RTV) a
      BCS class-II drug with known amorphous stabilizing small molecule Indomethacin
      (IND) by co-amorphous technology. The co-amorphous samples were prepared by
      solvent evaporation technique in the molar ratios RTV:IND (2:1), RTV:IND (1:1),
      RTV:IND (1:2) and their amorphous nature was confirmed by XRPD, DSC and FT-IR.
      Physical stability studies were carried out at temp 25 degrees C and 40 degrees C
      for maximum up to 90 days under dry conditions. Solubility and dissolution
      testing were carried out to investigate the dissolution advantage of prepared co
      amorphous systems. The amorphous mixtures of all tested molar ratios were found
      to become amorphous after solvent evaporation. The same was confirmed by
      detecting halo pattern in diffractograms of co-amorphous mixtures. The Tg values
      of all three systems were found to be more than 40 degrees C, the highest being
      51.88 degrees C for RTV:IND (2:1) system. Theoretical Tg values were calculated
      by Gordon-Taylor equation. Insignificant deviation of theoretical Tg values from
      that of practical one, corroborated by FT-IR studies showed no evidence of
      intermolecular interactions between RTV and IND. Almost 3-folds increase in the
      solubility for both amorphous RTV and IND was found as compared to their
      respective crystalline counterparts. The study demonstrated significant increase
      in the dissolution rate as well as increase in the total amount of drug dissolved
      for amorphous RTV, however it failed to demonstrate any significant improvement
      in the dissolution behavior of IND.

PMID- 24878387
TI  - Naringenin adds to the protective effect of L-arginine in monocrotaline-induced
      pulmonary hypertension in rats: favorable modulation of oxidative stress,
      inflammation and nitric oxide.
AB  - The present study was directed to investigate the possible modulatory effect of
      naringenin when co-administered with L-arginine in monocrotaline-induced
      pulmonary hypertension in rats. Pulmonary hypertension was induced by a single
      subcutaneous injection of monocrotaline (60 mg/kg). L-arginine (500 mg/kg) and
      naringenin (50 mg/kg) were orally administered daily, alone and in combination,
      for 3 weeks. Mean arterial blood pressure, electrocardiography and
      echocardiography were then recorded and rats were sacrificed and serum was
      separated for determination of total nitrate/nitrite level. Right ventricles and
      lungs were isolated for estimation of oxidative stress markers, tumor necrosis
      factor-alpha, total nitrate/nitrite and transforming growth factor-beta.
      Myeloperoxidase and caspase-3 activities in addition to endothelial and inducible
      nitric oxide synthase protein expression were also determined. Moreover,
      histological analysis of pulmonary arteries and cardiomyocyte cross-sectional
      area was performed. Combined therapy provided a significant improvement in L
      arginine protective effect toward preserving hemodynamic changes and alleviating
      oxidative stress, inflammatory and apoptotic markers induced by monocrotaline
      treatment. Furthermore, combined therapy prevented monocrotaline-induced changes
      in endothelial and inducible nitric oxide synthase protein expression as well as
      histological analysis compared with either treatment alone. In conclusion,
      naringenin significantly adds to the protective effect of L-arginine in pulmonary
      hypertension induced by monocrotaline in rats.

PMID- 24878388
TI  - Insulin aspart pharmacokinetics: an assessment of its variability and underlying
      mechanisms.
AB  - BACKGROUND: Insulin aspart (IAsp) is used by many diabetics as a meal-time
      insulin to control post-prandial glucose levels. As is the case with many other
      insulin types, the pharmacokinetics (PK), and consequently the pharmacodynamics
      (PD), is associated with clinical variability, both between and within
      individuals. The present article identifies the main physiological mechanisms
      that govern the PK of IAsp following subcutaneous administration and quantifies
      them in terms of their contribution to the overall variability. MATERIAL AND
      METHODS: CT scanning data from Thomsen et al. (2012) are used to investigate and
      quantify the properties of the subcutaneous depot. Data from Brange et al. (1990)
      are used to determine the effects of insulin chemistry in subcutis on the
      absorption rate. Intravenous (i.v.) bolus and infusion PK data for human insulin
      are used to understand and quantify the systemic distribution and elimination
      (Porksen et al., 1997; Sjostrand et al., 2002). PK and PD profiles for type 1
      diabetics from Chen et al. (2005) are analyzed to demonstrate the effects of IAsp
      antibodies in terms of bound and unbound insulin. PK profiles from Thorisdottir
      et al. (2009) and Ma et al. (2012b) are analyzed in the nonlinear mixed effects
      software Monolix(r) to determine the presence and effects of the mechanisms
      described in this article. RESULTS: The distribution of IAsp in the subcutaneous
      depot show an initial dilution of approximately a factor of two in a single
      experiment. Injected insulin hexamers exist in a chemical equilibrium with
      monomers and dimers, which depends strongly on the degree of dilution in
      subcutis, the presence of auxiliary substances, and a variety of other factors.
      Sensitivity to the initial dilution in subcutis can thus be a cause of some of
      the variability. Temporal variations in the PK are explained by variations in the
      subcutaneous blood flow. IAsp antibodies are found to be a large contributor to
      the variability of total insulin PK in a study by Chen et al. (2005), since only
      the free fraction is eliminated via the receptors. The contribution of these and
      other sources of variability to the total variability is quantified via a
      population PK analysis and two recent clinical studies (Thorisdottir et al.,
      2009; Ma et al., 2012b), which support the presence and significance of the
      identified mechanisms. CONCLUSIONS: IAsp antibody binding, oligomeric transitions
      in subcutis, and blood flow dependent variations in absorption rate seem to
      dominate the PK variability of IAsp. It may be possible via e.g. formulation
      design to reduce some of these variability factors.

PMID- 24878389
TI  - Thermally induced degradation pathways of three different antibody-based drug
      development candidates.
AB  - Protein-based medicinal products are prone to undergo a variety of chemical and
      physical degradation pathways. One of the most important exogenous stress
      condition to consider during manufacturing, transport and storage processes is
      temperature, because antibody-based therapeutics are only stable in a limited
      temperature range. In this study, three different formats of antibody-based
      molecules (IgG1, a bispecific scFv and a fab fragment) were exposed to thermal
      stress conditions occurring during transport and storage. For evaluation, an
      analytical platform was developed for the detection and characterization of
      relevant degradation pathways of different antibody-based therapeutics. The
      effect of thermal stress conditions on the stability of the three antibody-based
      formats was therefore investigated using visual inspection, different
      spectroscopic measurements, dynamic light scattering (DLS), differential scanning
      calorimetry (DSC), electrophoresis, asymmetric flow field-flow fractionation
      (AF4) and surface plasmon resonance technology (SPR). In summary, thermal stress
      led to heterogeneous chemical and physical degradation pathways of all three
      antibody-based formats used. In addition, identical exogenous stress conditions
      resulted in different kinds and levels of aggregates and fragmentation products.
      This knowledge is fundamental for a systematic and successful stabilization of
      protein-based therapeutics by the use of formulation additives. 

PMID- 24878390
TI  - State of the science: cervical cancer screening in transition.

PMID- 24878391
TI  - 2014 FIGO staging for ovarian, fallopian tube and peritoneal cancer.

PMID- 24878392
TI  - Bone-like mineral nucleating peptide nanofibers induce differentiation of human
      mesenchymal stem cells into mature osteoblasts.
AB  - A bone implant should integrate to the tissue through a bone-like mineralized
      interface, which requires increased osteoblast activity at the implant-tissue
      boundary. Modification of the implant surface with synthetic bioinstructive cues
      facilitates on-site differentiation of progenitor stem cells to functional mature
      osteoblasts and results in subsequent mineralization. Inspired by the bioactive
      domains of the bone extracellular matrix proteins and the mussel adhesive
      proteins, we synthesized peptide nanofibers to promote bone-like mineralization
      on the implant surface. Nanofibers functionalized with osteoinductive collagen I
      derived Asp-Gly-Glu-Ala (DGEA) peptide sequence provide an advantage in initial
      adhesion, spreading, and early commitment to osteogenic differentiation for
      mesenchymal stem cells (hMSCs). In this study, we demonstrated that this early
      osteogenic commitment, however, does not necessarily guarantee a priority for
      maturation into functional osteoblasts. Similar to natural biological cascades,
      early commitment should be further supported with additional signals to provide a
      long-term effect on differentiation. Here, we showed that peptide nanofibers
      functionalized with Glu-Glu-Glu (EEE) sequence enhanced mineralization abilities
      due to osteoinductive properties for late-stage differentiation of hMSCs. Mussel
      inspired functionalization not only enables robust immobilization on metal
      surfaces, but also improves bone-like mineralization under physiologically
      simulated conditions. The multifunctional osteoinductive peptide nanofiber
      biointerfaces presented here facilitate osseointegration for long-term clinical
      stability. 

PMID- 24878393
TI  - Manipulating magnetism: Ru25+ paddlewheels devoid of axial interactions.
AB  - Variable-temperature magnetic and structural data of two pairs of diruthenium
      isomers, one pair having an axial ligand and the formula Ru2(DArF)4Cl (where DArF
      is the anion of a diarylformamidine isomer and Ar = p-anisyl or m-anisyl) and the
      other one being essentially identical but devoid of axial ligands and having the
      formula [Ru2(DArF)4]BF4, show that the axial ligand has a significant effect on
      the electronic structure of the diruthenium unit. Variable temperature
      crystallographic and magnetic data as well as density functional theory
      calculations unequivocally demonstrate the occurrence of pi interactions between
      the p orbitals of the chlorine ligand and the pi* orbitals in the Ru2(5+) units.
      The magnetic and structural data are consistent with the existence of combined
      ligand sigma/metal sigma and ligand ppi/metal-dpi interactions. Electron
      paramagnetic resonance data show unambiguously that the unpaired electrons are in
      metal-based molecular orbitals. 

PMID- 24878394
TI  - Nucleic acid-based tissue biomarkers of urologic malignancies.
AB  - Molecular biomarkers play an important role in the clinical management of cancer
      patients. Biomarkers allow estimation of the risk of developing cancer; help to
      diagnose a tumor, ideally at an early stage when cure is still possible; and aid
      in monitoring disease progression. Furthermore, they hold the potential to
      predict the outcome of the disease (prognostic biomarkers) and the response to
      therapy (predictive biomarkers). Altogether, biomarkers will help to avoid tumor
      related deaths and reduce overtreatment, and will contribute to increased
      survival and quality of life in cancer patients due to personalized treatments.
      It is well established that the process of carcinogenesis is a complex interplay
      between genomic predisposition, acquired somatic mutations, epigenetic changes
      and genomic aberrations. Within this complex interplay, nucleic acids, i.e. RNA
      and DNA, play a fundamental role and therefore represent ideal candidates for
      biomarkers. They are particularly promising candidates because sequence-specific
      hybridization and amplification technologies allow highly accurate and sensitive
      assessment of these biomarker levels over a broad dynamic range. This article
      provides an overview of nucleic acid-based biomarkers in tissues for the
      management of urologic malignancies, i.e. tumors of the prostate, testis, kidney,
      penis, urinary bladder, renal pelvis, ureter and other urinary organs. Special
      emphasis is put on genomic, transcriptomic and epigenomic biomarkers (SNPs,
      mutations [genomic and mitochondrial], microsatellite instabilities, viral and
      bacterial DNA, DNA methylation and hydroxymethylation, mRNA expression, and non
      coding RNAs [lncRNA, miRNA, siRNA, piRNA, snRNA, snoRNA]). Due to the multitude
      of published biomarker candidates, special focus is given to the general
      applicability of different molecular classes as biomarkers and some particularly
      promising nucleic acid biomarkers. Furthermore, specific challenges regarding the
      development and clinical implementation of nucleic acid-based biomarkers are
      discussed.

PMID- 24878395
TI  - The experiences of rural and remote families involved in an inter-hospital
      transfer to a tertiary ICU: a hermeneutic study.
AB  - BACKGROUND: Inter-hospital transfers are necessary for critically ill patients to
      improve their chance of survival. Rural and remote families experience
      significant disruption to family life when critically ill patients are required
      to undergo a transfer to a tertiary hospital. What is not known is how ICU staff
      can assist these families who are involved in an inter-hospital transfer to a
      tertiary ICU. PURPOSE: To gain an understanding of rural and remote critical care
      families' experiences during an inter-hospital transfer to a tertiary ICU.
      METHOD: A hermeneutic phenomenological approach was adopted informed by the
      philosophical world views of Heidegger and Gadamer. Data collection occurred by
      in-depth conversational interviews from a purposeful sample of seven family
      members. Interview transcripts, field notes and diary entries formed the text
      which underwent hermeneutic analysis. FINDINGS: Being confused, being engaged,
      being vulnerable and being resilient emerged as significant aspects of the rural
      and remote family members' experience during a transfer event. CONCLUSION: A
      better understanding of the experiences of rural and remote families during an
      inter-hospital transfer journey can inform the practice of ICU nurses. This study
      highlights the specific experiences of rural and remote families during an inter
      hospital transfer journey to a tertiary ICU. It also informs nurses of the
      meaningful ways in which they can support these families with the uncertainty and
      chaos experienced as part of this journey.

PMID- 24878396
TI  - Accuracy of EMS Trauma Transport Destination Plans in North Carolina.
AB  - Abstract Objective. Planning for time-sensitive injury may allow emergency
      medical services (EMS) systems to more accurately triage patients meeting
      accepted criteria to facilities most capable of providing life-saving treatment.
      In 2010, North Carolina (NC) implemented statewide Trauma Triage and Destination
      Plans (TTDPs) in all 100 of North Carolina's county-defined EMS systems. Each
      system was responsible for identifying the specific destination hospitals with
      appropriate resources to treat trauma patients. We sought to characterize the
      accuracy of their hospital designations. Methods. In this cross-sectional study,
      we collected TTDPs for each county-defined EMS system, including their assigned
      hospital capabilities (i.e., trauma center or community hospital). We conducted a
      survey with each EMS system to determine how their TTDP was constructed and
      maintained, as well as with each TTDP-designated hospital to verify their
      capabilities. We determined the accuracy of the EMS assigned hospital
      designations by comparing them to the hospital's reported capabilities. Results.
      The 100 NC EMS systems provided 380 designations for 112 hospitals. TTDPs were
      created by EMS administrators and medical directors, with only 55% of EMS systems
      engaging a hospital representative in the plan creation. Compared to the actual
      hospital capabilities, 97% of the EMS TTDP designations were correct. Twelve
      hospital designations were incorrect and the majority (10) overestimated hospital
      capabilities. Of the 100 EMS systems, 7 misclassified hospitals in their TTDP.
      EMS systems that did not verify their local hospitals' capabilities during TTDP
      development were more likely to incorrectly categorize a hospital's capabilities
      (p = 0.001). Conclusions. A small number of EMS systems misclassified hospitals
      in their TTDP, but most plans accurately reflected hospital capabilities.
      Misclassification occurred more often in systems that did not consult local
      hospitals prior to developing their TTDP. The potential of the TTDP to improve
      communication between EMS agencies and the facilities with which they work has
      not been fully realized. EMS agencies or systems should verify local hospital
      capabilities when engaging in destination planning efforts.

PMID- 24878397
TI  - [Extravasation of contrast media at the puncture site: Strategies for managment].
AB  - The incidence of contrast medium extravasation at the venipuncture site has
      increased with the generalized use of automatic injectors. Most extravasations
      only cause slight edema and erythema. Nevertheless, in some cases extravasation
      can result in severe skin lesions or even in compartment syndrome. Lesions caused
      by extravasation usually resolve spontaneously with conservative treatment.
      Although the complications of extravasation are well known, institutional
      protocols are normally lacking and the criteria for taking action and the type of
      treatment, whether based on the literature or personal preferences, tend to vary.
      In this article, we review the incidence, risk factors, clinical manifestations,
      and options for preventing and treating contrast medium extravasation in soft
      tissues. Finally, we present the protocol we use to manage extravasation at our
      hospital. 

PMID- 24878399
TI  - Hypervalent iodine-promoted alpha-fluorination of acetophenone derivatives with a
      triethylamine.HF complex.
AB  - The direct fluorination reaction of acetophenone using iodosylarenes and TEA.5HF
      was conducted under mild conditions except for use of a HF reagent. The
      fluorination reaction was applied to acetophenone derivatives, acetonaphthones,
      benzyl phenyl ketone, propiophenone, butyrophenone, 1-indanone, and phenacyl
      chloride, giving selectively the corresponding alpha-fluoroketone derivatives in
      good yields. 

PMID- 24878400
TI  - Make your trappings count: the mathematics of pest insect monitoring. Comment on
      "Multiscale approach to pest insect monitoring: random walks, pattern formation,
      synchronization, and networks" by Petrovskii et al.

PMID- 24878401
TI  - Measuring patient-perceived hospital service quality: validity and managerial
      usefulness of HCAHPS scales.
AB  - This study extends previous efforts to validate the Consumer Assessment of
      Healthcare Providers & Systems Hospital Survey (HCAHPS) instrument. Data from two
      non-profit hospitals are used to explore psychometric properties of the HCAHPS
      measures. The findings raise concerns that HCAHPS measures may not meet the
      standards for reliability and validity. The results are mixed in terms of the
      impact of HCAHPS dimensions on overall quality ratings of hospitals. Implications
      of the results are discussed and future research avenues are offered regarding
      the use and further refinement of the HCAHPS measures. 

PMID- 24878398
TI  - What do we really know about the safety of tai chi?: A systematic review of
      adverse event reports in randomized trials.
AB  - OBJECTIVE: To systematically review the frequency and quality of adverse event
      (AE) reports in randomized controlled trials (RCTs) of tai chi (TC). DATA
      SOURCES: Electronic searches of PubMed/MEDLINE and additional databases from
      inception through March 2013 of English-language RCTs. Search terms included tai
      chi, taiji, and tai chi chuan. Data were independently extracted by 2
      investigators. STUDY SELECTION: We included all available RCTs that were
      published in English and used TC as an intervention. Inclusion and exclusion
      criteria of studies were reported in accordance with the Preferred Reporting
      Items for Systematic Reviews and Meta-Analyses guidelines. DATA EXTRACTION:
      Eligible RCTs were categorized with respect to AE reporting: no mention of
      protocol for monitoring AEs or reports of AEs, and reports of AEs either with or
      without explicit protocol for monitoring AEs. DATA SYNTHESIS: There were 153
      eligible RCTs identified; most targeted older adults. Only 50 eligible trials
      (33%) included reporting of AEs; of these, only 18 trials (12% overall) also
      reported an explicit AE monitoring protocol. Protocols varied with respect to the
      rigor of systematic monitoring in both the TC and comparison groups. Reported AEs
      were typically minor and expected and primarily musculoskeletal related (eg, knee
      and back pain); no intervention-related serious AEs were reported. CONCLUSIONS:
      TC is unlikely to result in serious AEs, but it may be associated with minor
      musculoskeletal aches and pains. However, poor and inconsistent reporting of AEs
      greatly limits the conclusions that can be drawn regarding the safety of TC.

PMID- 24878402
TI  - Literally experts: expertise and the processing of analogical metaphors in
      pharmaceutical advertising.
AB  - This research examined differences between novices and experts in processing
      analogical metaphors appearing in prescription drug advertisements. In contrast
      to previous studies on knowledge transfer, no evidence of the superiority of
      experts in processing metaphors was found. The results from an experiment suggest
      that expert consumers were more likely to process a metaphor in an ad literally
      than novices. Our findings point to a condition in which the expertise effect
      with processing analogies is not the linear relationship assumed in previous
      studies. 

PMID- 24878403
TI  - Is advertising by dental professionals having a negative impact on consumers?:
      the perspectives of Indian consumers.
AB  - Advertising by dentists is a controversial issue. Many feel that advertising is
      necessary for creating dental awareness, whereas, many others feel that it should
      be banned to keep intact the ethical aspect of the profession, which aims at
      serving the community. This study explores consumers' ideas about advertising. A
      total of 562 respondents from various parts of India participated in this study.
      The response rate was 46.83%. The data were analyzed by applying the chi-square
      test of association and the Z test of difference between two proportions at 5%
      and 1% level of significance (i.e., p<.05 and p<.01).

PMID- 24878404
TI  - Variables associated with seeking information from doctors and the internet after
      exposure to direct-to-consumer advertisements for prescription medications.
AB  - This study examines variables associated with seeking information from doctors,
      the Internet, and a combination of both doctors and Internet after exposure to
      direct-to-consumer advertisements. Data were analyzed from 462 college students.
      Younger age, women, and health insurance were associated with greater odds for
      doctor; women, subjective norms, intentions, and greater time since seen doctor
      were associated with greater odds for Internet; and African American, Hispanic,
      subjective norms, intentions, and health insurance were associated with greater
      odds for both doctor and Internet. Marketers of direct-to-consumer advertisements
      can use these findings for tailoring and targeting direct-to-consumer
      advertisements. 

PMID- 24878405
TI  - Factors influencing nursing career choices and choice of study program.
AB  - In advance of a recruitment campaign, Israeli first-year nursing students of all
      ethnicities were surveyed to elucidate what factors had influenced them to make
      nursing their career and what sort of training track they preferred. The
      responses made it clear that different factors influence different groups
      differently. There were noticeable differences by gender, age, and ethnicity.
      Overall, training institutions were chosen for their closeness to the student's
      home but other factors also operated among particular groups, such as
      institutional prestige and flexible entry criteria. There was a blatant
      preference for academic, particularly university-sited, programs over diploma
      programs. 

PMID- 24878406
TI  - Using Web 2.0 for health promotion and social marketing efforts: lessons learned
      from Web 2.0 experts.
AB  - Web 2.0 experts working in social marketing participated in qualitative in-depth
      interviews. The research aimed to document the current state of Web 2.0 practice.
      Perceived strengths (such as the viral nature of Web 2.0) and weaknesses (such as
      the time consuming effort it took to learn new Web 2.0 platforms) existed when
      using Web 2.0 platforms for campaigns. Lessons learned were identified--namely,
      suggestions for engaging in specific types of content creation strategies (such
      as plain language and transparent communication practices). Findings present
      originality and value to practitioners working in social marketing who want to
      effectively use Web 2.0.

PMID- 24878407
TI  - Scarf osteotomy.
AB  - The term scarf osteotomy was first used by Weil when presenting his results from
      more than 1000 cases. Scarf is a carpentry term describing beveling the ends of 2
      pieces of wood and securely fastening them so that they overlap to create one
      continuous piece. This technique was popularized by Weil and Barouk as a
      versatile method of correcting hallux valgus while maintaining the blood supply
      to the metatarsal head. It also has rigid fixation, allowing early mobilization.
      This article addresses the surgical technique of the scarf osteotomy together
      with the results and complications of hallux valgus correction. 

PMID- 24878408
TI  - Minimally invasive osteotomies.
AB  - As orthopedic surgery continues to head in the direction of less invasive
      surgical techniques, this article explores the application and evolution of
      minimally invasive/percutaneous techniques in the surgical correction of hallux
      valgus deformities. Modern techniques are described and available literature is
      reviewed. 

PMID- 24878409
TI  - Correction of moderate and severe hallux valgus deformity with a distal
      metatarsal osteotomy using an intramedullary plate.
AB  - More than 200 surgeries have been described for hallux valgus correction. The
      distal V-shape chevron-type osteotomy was described with no more than 50%
      translation of the distal fragment in relation to the metatarsal shaft. This
      concept of high, powerful correction for distal chevron osteotomy fixed by the
      Mini MaxLock Extreme ISO gives the surgeon the possibility of a mini-invasive
      rapid solution. A new technique of fixation is based on the Murawski and Beskin
      concept, because a powerful correction can be performed with a minimally invasive
      approach, but, in contrast to other studies, with stable osteotomy fixation. 

PMID- 24878410
TI  - Rotational and opening wedge basal osteotomies.
AB  - There are more than 150 different procedures described for correction of the
      hallux valgus deformity, the treatment of which is usually guided by severity.
      Moderate to severe hallux valgus has traditionally been managed with a shaft or
      proximal osteotomy together with distal soft-tissue release. Proximal osteotomies
      can be classified as translation or rotational. Rotational osteotomies such as
      the Ludloff and proximal opening wedge have not been popular historically because
      of instability from lack of fixation, resulting in complications. This article
      describes modified techniques with modern fixation of these 2 osteotomies, which
      offer stable fixation and reproducible results. 

PMID- 24878411
TI  - The modified Lapidus fusion.
AB  - Due to its proximal correction site and long lever arm, the Lapidus fusion,
      modified or not, is a powerful technique to correct hallux valgus deformities.
      The disadvantages are a high complication rate and a long postoperative
      rehabilitation period. It is only performed in 5% to 10% of all hallux valgus
      deformity corrections but remains, however, an important procedure, especially in
      moderate to severe deformities with intermetatarsal angles more than 14 degrees ,
      hypermobility of the first ray, arthritis of the first tarsometatarsal joint, and
      recurrent deformities. This article provides an overview of the procedure with
      special focus on the surgical technique. 

PMID- 24878412
TI  - Pediatric hallux valgus.
AB  - Hallux valgus in children is a relatively uncommon deformity, also known by
      several other names such as juvenile or adolescent bunion, metatarsus primus
      varus, and metatarsus primus adductus. The presence of an open growth plate is
      considered by most to be part of the definition of this condition. However,
      others include patients up to age 20 years, owing to the plastic nature of the
      various components of the condition. The presenting complaint is invariably of
      the bunion and its cosmetic appearance. Treatment should be conservative and
      surgery avoided till skeletal maturity is achieved due to the high incidence of
      recurrence in children. 

PMID- 24878414
TI  - Recurrence of hallux valgus: a review.
AB  - Recurrence of hallux valgus deformity can be a common complication after
      corrective surgery. The cause of recurrent hallux valgus is usually
      multifactorial, and includes patient-related factors such as preoperative
      anatomic predisposition, medical comorbidities, compliance with postcorrection
      instructions, and surgical factors such as choice of the appropriate procedure
      and technical competency. For a successful outcome, this cause must be
      ascertained preoperatively. Although the algorithm to determine which
      intervention should be used is not unlike that of primary hallux valgus surgery,
      operative correction of hallux valgus recurrence can be challenging. This article
      discusses these challenges, complications, causes, and techniques. 

PMID- 24878413
TI  - First metatarsophalangeal arthrodesis for hallux valgus.
AB  - Arthrodesis of the first metatarsophalangeal joint is a reliable operation in the
      treatment of selected cases of hallux valgus. It corrects deformity of hallux
      valgus and metatarsus primus varus, leading to good functional results with a low
      complication rate. It is a technique well suited to patients with hallux valgus
      associated with degenerative changes or severe deformity, and those for whom
      primary hallux valgus surgery has failed. 

PMID- 24878415
TI  - The treatment of iatrogenic hallux varus.
AB  - Though uncommon, iatrogenic hallux varus is most often the result of
      overresection of the medial eminence, overtranslation of an osteotomy,
      overrelease of the lateral soft tissues, or overtightening of the medial tissues.
      It is not always symptomatic, as the degree of deformity can be well tolerated.
      For soft-tissue reconstructions, releases have little role to play unless minor
      deformity is detected early on and the longevity of tendon transfer and tenodesis
      remains unknown. For bony reconstruction, arthrodesis is the recommended salvage
      technique. 

PMID- 24878416
TI  - Transfer metatarsalgia post hallux valgus surgery.
AB  - Metatarsalgia, pain around the metatarsophalangeal joints, may arise from
      mechanical causes spontaneously or iatrogenically. Nonunion or malunion of the
      first metatarsal can transfer weight-bearing forces and overload the lesser
      metatarsals. Transfer metatarsalgia after failed hallux valgus surgery is
      troublesome and more prevalent than would be expected. Clinical examination of
      the patient allows identifying the type of transfer metatarsalgia and
      pathomechanics involved. This review focuses on transfer metatarsalgia after
      hallux valgus surgery and provides a basic understanding of the pathomechanics,
      clinical examination, and image studies. It also addresses the options for both
      conservative and surgical treatment of this challenging condition. 

PMID- 24878417
TI  - Treatment of shortening following hallux valgus surgery.
AB  - Transfer metatarsalgia is a recognized complication following hallux valgus
      surgery, usually as a result of shortening of the first metatarsal. In this
      article, the authors present an overview of the incidence, presentation, and
      treatment strategies employed in its management. 

PMID- 24878418
TI  - Management of primary and revision hallux valgus.

PMID- 24878419
TI  - [Using e-mail as a means of communicating analytical results. Is it effective?].

PMID- 24878420
TI  - Immunotherapy for non-small-cell lung cancer.
AB  - Activation of the host immune system represents an attractive treatment approach
      for cancers. In non-small-cell lung cancer (NSCLC), a variety of immunotherapies,
      including nonspecific immune stimulants, vaccines and checkpoint inhibitors, have
      been evaluated in clinical trials. Several randomized Phase III trials have
      failed to demonstrate clinical benefit from nonspecific immune stimulants and
      vaccines in the overall trial populations. Activity of vaccines in subsets of
      patients in these trials needs further evaluation. Unlike vaccines aimed at
      stimulating a cellular immune response to antigens differentially expressed in
      cancers, checkpoint inhibitors aim at overcoming immune inhibitory signals in the
      tumor microenvironment via pharmacological inhibition of immune checkpoints - a
      crucial tumoral immune escape mechanism. Early clinical trials of checkpoint
      inhibitors showed promising results with some durable responses. Better
      understanding of the mechanisms of immunosuppression specific to NSCLC will be
      crucial for successful patient selection for immunotherapy.

PMID- 24878421
TI  - Stability of cough reflex sensitivity during viral upper respiratory tract
      infection (common cold).
AB  - Cough is among the symptoms most commonly associated with an acute, viral upper
      respiratory tract infection (URI), such as the common cold. Two previous studies
      incorporating capsaicin cough challenge methodology have demonstrated that cough
      reflex sensitivity is transiently enhanced during URI. These studies used single
      measurements of cough reflex sensitivity during the URI period. To our knowledge,
      no previous studies have included multiple measurements of cough reflex
      sensitivity to capsaicin during a URI to evaluate the stability of this measure
      during the acute viral illness. In the current methodological investigation, we
      performed capsaicin cough challenges in 42 subjects with URI who were otherwise
      healthy, adult, nonsmokers (25 female). Subjects were enrolled within 72 h of
      onset of illness and randomly assigned to 3 groups (n = 14 each) that underwent
      cough reflex sensitivity measurement (C2 and C5) at days 0 and 1 for group 1;
      days 2 and 3 for group 2; or days 4 and 5 for group 3. Each subject returned 4-8
      weeks post-viral infection to establish a healthy baseline measurement
      (recovery). Our results support that cough reflex sensitivity to capsaicin, as
      measured by C5, is a sensitive measure that remains stable during 6 days of a
      URI. These results suggest that cough reflex sensitivity measures in the presence
      of a URI provide a sensitive and reproducible approach that could be used in
      future investigations seeking to test experimental antitussive therapies. 

PMID- 24878422
TI  - New antimicrobial approaches to gram positive respiratory infections.
AB  - Nowadays, we face growing resistance among gram-positive and gram-negative
      pathogens that cause respiratory infection in the hospital and in the community.
      The spread of penicillin- and macrolide-resistant pneumococci, Community-acquired
      methicillin-resistant staphylococcus aureus (Ca-MRSA), the emergence of
      glycopeptide-resistant staphylococci underline the need for underline the need
      for therapeutic alternatives. A number of new therapeutic agents, with activity
      against the above Gram (+) respiratory pathogens, as ceftaroline, ceftopibrole,
      telavancin, tedizolid have become available, either in clinical trials or have
      been approved for clinical use. Especially, the development of new oral
      antibiotics, as nemonaxacin, omadacyclin, cethromycin and solithromycin will give
      a solution to the lack of oral drugs for outpatient treatment. In the future the
      clinician needs to optimize the use of old and new antibiotics to treat gram (+)
      respiratory serious infections. 

PMID- 24878424
TI  - Montelukast-loaded nanostructured lipid carriers: part I oral bioavailability
      improvement.
AB  - The purpose of the study was to formulate montelukast-loaded nanostructured lipid
      carrier (MNLC) to improve its systemic bioavailability, avoid hepatic metabolism
      and reduce hepatic cellular toxicity due to metabolites. MNLC was prepared using
      melt-emulsification-homogenization method. Preformulation study was carried out
      to evaluate drug-excipient compatibility. MNLCs were prepared using spatially
      different solid and liquid lipid triglycerides. CAE (DL-Pyrrolidonecarboxylic
      acid salt of L-cocyl arginine ethyl ester), a cationic, biodegradable,
      biocompatible surfactant was used to stabilize the system. MNLCs were
      characterized by FTIR, XRPD and DSC to evaluate physicochemical properties. MNLCs
      having a particle size of 181.4 +/- 6.5 nm with encapsulation efficiency of 96.13
      +/- 0.98% were prepared. FTIR findings demonstrated no interaction between the
      drug and excipients of the formulation which could lead to asymmetric vibrations.
      DSC and XRPD study confirmed stable amorphous form of the montelukast in lipid
      matrix. In vitro release study revealed sustained release over a period of 24 h.
      In vivo single dose oral pharmacokinetic study demonstrated 143-fold improvement
      in bioavailability as compared to montelukast-aqueous solution. Thus, the result
      of this study implies that developed MNLC formulation be suitable to sustain the
      drug release with improvement in the bioavailability.

PMID- 24878425
TI  - Pollen developmental defects in ZD-CMS rice line explored by cytological,
      molecular and proteomic approaches.
AB  - Cytoplasmic male sterility (CMS) is a widely observed phenomenon, which is
      especially useful in hybrid seed production. Meixiang A (MxA) is a new rice CMS
      line derived from a pollen-free sterile line named Yunnan ZidaoA (ZD-CMS). In
      this study, a homologous WA352 gene with variation in two nucleotides was
      identified in MxA. Cytological analysis revealed that MxA was aborted in the
      early uninucleate stage. The protein expression profiles of MxA and its
      maintainer line MeixiangB (MxB) were systematically compared using iTRAQ-based
      quantitative proteomics technology using young florets at the early uninucleate
      stage. A total of 688 proteins were quantified in both rice lines, and 45 of
      these proteins were found to be differentially expressed. Bioinformatics analysis
      indicated a large number of the proteins involved in carbohydrate metabolism or
      the stress response were downregulated in MxA, suggesting that these metabolic
      processes had been hindered during pollen development in MxA. The ROS (reactive
      oxygen species) level was increased in the mitochondrion of MxA, and further
      ultrastructural analysis showed the mitochondria with disrupted cristae in the
      rice CMS line MxA. These findings substantially contribute to our knowledge of
      pollen developmental defects in ZD-CMS rice line. BIOLOGICAL SIGNIFICANCE:
      MeixiangA (MxA) is a new type of rice CMS line, which is derived from pollen-free
      sterile line Yunnan ZidaoA. In this study, the cytological, molecular and
      proteomic approaches were used to study the characteristics of this new CMS line.
      Cytological study indicates the CMS line is aborted at the early uninucleate
      stage. A potential sterile gene ZD352 is identified in MxA, the protein product
      of which is mainly accumulated at the MMC/Meiotic stage. iTRAQ based proteomic
      analysis is performed to study the relevant proteins involved in the CMS
      occurance, 45 proteins are found to be significant differentially expressed and
      these proteins are involved in many cellular processes such as carbohydrate
      metabolism, stress response, protein synthesis. To our knowledge, this is the
      first report using the iTRAQ-labeled quantitative proteomic to study the protein
      expression variation during the abortion processes between a CMS line and its
      maintainer line. These results provide new insights on the CMS mechanisms of ZD
      CMS rice line.

PMID- 24878426
TI  - Improved prediction of peptide detectability for targeted proteomics using a rank
      based algorithm and organism-specific data.
AB  - The in silico prediction of the best-observable "proteotypic" peptides in mass
      spectrometry-based workflows is a challenging problem. Being able to accurately
      predict such peptides would enable the informed selection of proteotypic peptides
      for targeted quantification of previously observed and non-observed proteins for
      any organism, with a significant impact for clinical proteomics and systems
      biology studies. Current prediction algorithms rely on physicochemical parameters
      in combination with positive and negative training sets to identify those peptide
      properties that most profoundly affect their general detectability. Here we
      present PeptideRank, an approach that uses learning to rank algorithm for peptide
      detectability prediction from shotgun proteomics data, and that eliminates the
      need to select a negative dataset for the training step. A large number of
      different peptide properties are used to train ranking models in order to predict
      a ranking of the best-observable peptides within a protein. Empirical evaluation
      with rank accuracy metrics showed that PeptideRank complements existing
      prediction algorithms. Our results indicate that the best performance is achieved
      when it is trained on organism-specific shotgun proteomics data, and that
      PeptideRank is most accurate for short to medium-sized and abundant proteins,
      without any loss in prediction accuracy for the important class of membrane
      proteins. BIOLOGICAL SIGNIFICANCE: Targeted proteomics approaches have been
      gaining a lot of momentum and hold immense potential for systems biology studies
      and clinical proteomics. However, since only very few complete proteomes have
      been reported to date, for a considerable fraction of a proteome there is no
      experimental proteomics evidence that would allow to guide the selection of the
      best-suited proteotypic peptides (PTPs), i.e. peptides that are specific to a
      given proteoform and that are repeatedly observed in a mass spectrometer. We
      describe a novel, rank-based approach for the prediction of the best-suited PTPs
      for targeted proteomics applications. By building on methods developed in the
      field of information retrieval (e.g. web search engines like Google's PageRank),
      we circumvent the delicate step of selecting positive and negative training sets
      and at the same time also more closely reflect the experimentalist's need for
      selecting e.g. the 5 most promising peptides for targeting a protein of interest.
      This approach allows to predict PTPs for not yet observed proteins or for
      organisms without prior experimental proteomics data such as many non-model
      organisms.

PMID- 24878427
TI  - Comparative proteomic analysis reveals the suppressive effects of dietary high
      glucose on the midgut growth of silkworm.
AB  - The silkworm, Bombyx mori, is an important model of lepidoptera insect, and it
      has been used for several models of human diseases. In human being, long-term
      high-sugar diet can induce the occurrence of diabetes and other related diseases.
      Interestingly, our experiments revealed the high glucose diet also has a
      suppressive effect on the development of silkworms. To investigate the molecular
      mechanism by which high-glucose diet inhibited the midgut growth in silkworms, we
      employed comparative proteomic analysis to globally identify proteins
      differentially expressed in normal and high-glucose diet group silkworms. In all,
      28 differently proteins were suppressed and 5 proteins induced in high-glucose
      diet group. Gene ontology analysis showed that most of these differently proteins
      are mainly involved in metabolic process, catalytic and cellular process. A
      development related protein, imaginal disk growth factor (IDGF), was further
      confirmed by western blot exclusively expressing in the normal diet group
      silkworms. Taken together, our data suggests that IDGF plays a critical role in
      impairing the development of silkworms by a high-glucose diet. BIOLOGICAL
      SIGNIFICANCE: Glucose has been thought to play essential roles in growth and
      development of silkworm. In this paper, we certified firstly that high-glucose
      diet can suppress the growth of silkworm, and comparative proteomic was employed
      to reveal the inhibition mechanism. Moreover, an important regulation related
      protein (IDGF) was found to involve in this inhibition process. These results
      will help us get a deeper understanding of the relationship between diet and
      healthy. Furthermore, IDGF may be the critical protein for reducing the blood
      sugar in silkworm, and it may be used for screening human hypoglycemic drug. The
      work has not been submitted elsewhere for publication, in whole or in part, and
      all the authors have approved the manuscript.

PMID- 24878423
TI  - Prediction and redesign of protein-protein interactions.
AB  - Understanding the molecular basis of protein function remains a central goal of
      biology, with the hope to elucidate the role of human genes in health and in
      disease, and to rationally design therapies through targeted molecular
      perturbations. We review here some of the computational techniques and resources
      available for characterizing a critical aspect of protein function - those
      mediated by protein-protein interactions (PPI). We describe several applications
      and recent successes of the Evolutionary Trace (ET) in identifying molecular
      events and shapes that underlie protein function and specificity in both
      eukaryotes and prokaryotes. ET is a part of analytical approaches based on the
      successes and failures of evolution that enable the rational control of PPI. 

PMID- 24878429
TI  - Psychological predictors of functional outcome in people with schizophrenia.
AB  - BACKGROUND: There is increasing evidence that psychological factors (e.g.,
      defeatist performance beliefs, trait negative affect) contribute to poor
      functional outcome in people with schizophrenia. In the current study, we
      evaluated whether multiple psychological factors predict poor functional outcome
      in individuals with schizophrenia, and whether associations between psychological
      variables and functional outcome persist even after accounting for
      neuropsychological impairment and negative symptoms. METHODS: 100 patients
      meeting diagnostic criteria for schizophrenia or schizoaffective disorder and 78
      demographically matched healthy control subjects completed self-report
      psychological measures, neuropsychological testing, and clinical rating scales.
      RESULTS: Self-report scales assessing negative affectivity, defeatist performance
      beliefs, anhedonia, and behavioral inhibition were significantly correlated with
      functional outcome in people with schizophrenia. Neuropsychological impairment
      was associated with vocational outcome, whereas most of the self-report measures
      were related to social outcome. Defeatist performance attitudes were not
      correlated with neuropsychological performance. CONCLUSIONS: Self-report measures
      predict variance in functional outcome beyond measures of clinical symptomatology
      and neuropsychological impairment. Findings indicate that psychological factors
      may be meaningful targets for psychosocial interventions aimed at improving
      functional outcome in schizophrenia.

PMID- 24878428
TI  - Prognostic implications of the standardized study of resection margins in
      pancreatic cancers.
AB  - INTRODUCTION: Involvement of surgical resection margins is a fundamental
      prognostic factor in pancreatic oncological surgery. However, there is a lack of
      standardized histopathology definition. The aims of this study are to investigate
      the real rate of R1 resections when surgical specimens are evaluated according to
      a standardized protocol and to study its survival implications. PATIENTS Y
      METHODS: One hundred consecutive surgically resected patients with pancreatic
      ductal adenocarcinoma were included in the study. They were further divided in 2
      groups: pre-protocol, evaluated before the introduction of the standardized
      protocol and post-protocol, analyzed with the standardized protocol. RESULTS: R0
      resection rate in the pre-protocol group was 78%, falling to 47% after the
      introduction of the standardized protocol (p=0,003). The posterior
      retroperitoneal margin was the most frequently involved margin. In cases with
      tumors located at the pancreatic head and analyzed according to the standardized
      protocol R1 involvement negatively affected survival. Median survival in the R0
      group was 22 months versus 16 in those with the margin involved (HR: 2.044; IC
      95% 1,00-4,16; P=.043). CONCLUSIONS: Standardized evaluation of the
      retroperitoneal margins in pancreatic cancer increases the rate of R1 patients.
      In cases with pancreatic cancer located at the pancreatic head involvement of
      posterior retroperitoneal margin significantly decreases survival.

PMID- 24878430
TI  - Novel rare variants in F-box protein 45 (FBXO45) in schizophrenia.
AB  - The ubiquitin ligase F-box protein 45 (FBXO45) is critical for synaptogenesis,
      neuronal migration, and synaptic transmission. FBXO45 is included in the 3q29
      microdeletion region that confers a significant risk for schizophrenia, as shown
      by rare structural variant studies. Thus, FBXO45 is considered a prominent
      candidate for mediating schizophrenia pathogenesis. Here, we investigated rare,
      deleterious single nucleotide variants (SNVs) as well as small insertions and
      deletions (INDELs) in FBXO45 that may contribute to schizophrenia susceptibility.
      Using Sanger sequencing, we performed mutation screening in FBXO45 exon regions
      in 337 schizophrenia patients. Novel missense or nonsense variants were followed
      up with a genetic association study in an independent sample set of 601
      schizophrenia patients and 916 controls, a case report for assessing the clinical
      consequence of the mutations, a pedigree study for measuring mutation inheritance
      in the proband's family, bioinformatics analyses for evaluating mutation effect
      on protein structure and function, and mRNA expression analysis for examining
      mutation transcriptional influence on FBXO45 expression. One heterozygous, novel,
      and rare missense mutation (R108C) was identified in a single schizophrenia
      patient and in his healthy mother. At age 20, this patient was diagnosed with
      paranoid schizophrenia and carried some clinical features of 3q29 deletion
      phenotypes, including premorbid IQ decline. With follow-up genotyping, this
      mutation was not found in either the schizophrenia group (0/601) or the healthy
      control group (0/916). Bioinformatics analyses predicted that R108C probably
      pathologically impacted the structure and function of the FBXO45 protein. The
      relative expression of FBXO45 in SCZ case with R108C mutation was relatively low
      when compared to 50 schizophrenia patients and 52 healthy controls. The R108C
      mutation in FBXO45 is a rare variant with a modest effect on schizophrenia risk
      that may disrupt the structure and function of the FBXO45 protein. Our findings
      also suggest that FBXO45 may be a new attractive candidate gene for
      schizophrenia. 

PMID- 24878432
TI  - Dispersed-nanoparticle loading synthesis for monodisperse Au-titania composite
      particles and their crystallization for highly active UV and visible
      photocatalysts.
AB  - Submicrometer-sized amorphous titania spheres incorporating Au nanoparticles
      (NPs) were prepared in a one-pot synthesis consisting of a sol-gel reaction of
      titanium(IV) isopropoxide in the presence of chloroauric acid and a successive
      reduction with sodium borohydride in a mixed solvent of ethanol/acetonitrile. The
      synthesis was allowed to prepare monodisperse titania spheres that homogeneously
      incorporated Au NPs with sizes of ca. 7 nm. The Au NP-loaded titania spheres
      underwent different crystallization processes, including 500  degrees C
      calcination in air, high-temperature hydrothermal treatment (HHT), and/or low
      temperature hydrothermal treatment (LHT). Photocatalytic experiments were
      conducted with the Au NP-loaded crystalline titania spheres under irradiation of
      UV and visible light. A combined process of LHT at 80  degrees C followed by
      calcination at 500  degrees C could effectively crystallize titania spheres
      maintaining the dispersion state of Au NPs, which led to photocatalytic activity
      higher than that of commercial P25 under UV irradiation. Under visible light
      irradiation, the Au NP-titania spheres prepared with a crystallization process of
      LHT at 80  degrees C for 6 h showed photocatalytic activity much higher than a
      commercial product of visible light photocatalyst. Structure analysis of the
      visible light photocatalysts indicates the importance of prevention of the Au NPs
      aggregation in the crystallization processes for enhancement of photocatalytic
      activity. 

PMID- 24878433
TI  - Risk of arterial thromboembolic events with vascular endothelial growth factor
      receptor tyrosine kinase inhibitors: an up-to-date meta-analysis.
AB  - PURPOSE: Arterial thromboembolic events (ATEs) with vascular endothelial growth
      factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) have emerged as a serious
      concern, we perform a meta-analysis of randomized controlled trials (RCTs) to
      determine the incidence and risk of ATEs in cancer patients treated with these
      agents. METHODS: The databases of PubMed and Web of Science were searched for
      relevant articles. Statistical analyses were conducted to calculate the summary
      incidence, odds ratio (OR), and 95% confidence intervals (CIs) by using either
      random effects or fixed effect models according to the heterogeneity of included
      studies. RESULTS: A total of 9711 patients from 19 RCTs were included. The
      overall incidence of ATEs was 1.5% (95%CI: 1.0-2.3%). The use of VEGFR-TKIs
      significantly increased the risk of developing ATEs when compared with controls
      (OR 2.26, 95%CI: 1.38-3.68, p=0.001). Sensitivity analysis indicated that the
      significance estimate of pooled ORs was not significantly influenced by omitting
      any single study. In subgroup analyses, the odds ratio of ATEs did not
      significantly vary with tumor types (p=0.70), VEGFR-TKIs (p=0.32), treatment
      regimens (p=0.76), phase of trials (p=0.37) and sample size (p=0.89).
      Additionally, the most common events for ATEs were cardiac ischemia/infarction
      (67.4%), CNS ischemia (7.9%) and cerebrovascular accident (6.7%). CONCLUSION: In
      this largest meta-analysis to date, we find that treatment with VEGFR-TKIs
      significantly increase the risk of developing ATEs. Further studies are still
      needed to investigate this association. In the appropriate clinical scenario, the
      use of these drugs remains justified in their approved indications.

PMID- 24878431
TI  - Potential role of the combination of galantamine and memantine to improve
      cognition in schizophrenia.
AB  - The Measurement and Treatment Research to Improve Cognition in Schizophrenia
      (MATRICS) and Treatment Units for Research on Neurocognition and Schizophrenia
      projects were designed to facilitate the development of new drugs for the
      treatment of cognitive impairments in people with schizophrenia. The MATRICS
      project identified three drug mechanisms of particular interest: dopaminergic,
      cholinergic, and glutamatergic. As a group, while people with schizophrenia have
      moderate cognitive impairment, it is the best predictor of long-term outcome.
      Unfortunately, there are no approved medications for cognitive impairment in this
      population. Hence, the development of new pharmacological approaches is critical
      for reducing illness-related disability. The combination of an
      acetylcholinesterase inhibitor (AChEI) and memantine is more effective than
      either medication alone to improve cognition in Alzheimer's dementia. Galantamine
      is not only an AChEI, but also a positive allosteric modulator of the alpha4beta2
      and alpha7 nicotinic receptors. Hypofunction of N-methyl-d-aspartate (NMDA)
      receptors has been implicated in the pathophysiology of cognitive symptoms in
      schizophrenia and hence memantine may positively impact cognition. Memantine
      decreases the tonic NMDA current and galantamine enhances the action potential
      mediated by a postsynaptic NMDA current. This results in an increased signal
      transmission; therefore, a greater signal-to-noise ratio occurs with the
      combination than memantine alone. Galantamine improves the alpha-amino-3-hydroxy
      5-methyl-4-isoxazol-propionate (AMPA)-mediated signaling which could be
      neuroprotective and may improve memory coding. The combination of galantamine and
      memantine may be particularly effective in schizophrenia in order to increase the
      selective cognition enhancement produced by either medication alone. In the
      future, multitarget-directed ligands may play a role in the treatment of complex
      diseases like schizophrenia. 

PMID- 24878434
TI  - Complexes between hypohalous acids and phosphine derivatives. Pnicogen bond
      versus halogen bond versus hydrogen bond.
AB  - The complexes of HOBr:PH2Y (Y=H, F, Cl, Br, CH3, NH2, OH, and NO2), HOCl:PH2F,
      and HOI:PH2F have been investigated with ab initio calculations at the MP2/aug-cc
      pVTZ level. Four types of structures (1, 2, 3a, and 3b) were observed for these
      complexes. 1 is stabilized by an O?P pnicogen bond, 2 by a P?X halogen bond, 3a
      by a H?P hydrogen bond and a P?X pnicogen bond, and 3b by H?P and H?Br hydrogen
      bonds. Their relative stability is related to the halogen X of HOX and the
      substituent Y of PH2Y. These structures can compete with interaction energy of 
      10.22~-29.40 kJ/mol. The HO stretch vibration shows a small red shift in 1, a
      small irregular shift in 2, but a prominent red shift in 3a and 3b. The XO
      stretch vibration exhibits a smaller red shift in 1, a larger red shift in 2, but
      an insignificant blue shift in 3a and 3b. The PY stretch vibration displays a red
      shift in 1 but a blue shift in 2, 3a, and 3b. The formation mechanism, stability,
      and properties of these structures have been analyzed with molecular
      electrostatic potentials, orbital interactions, and non-covalent interaction
      index.

PMID- 24878435
TI  - Effect of gemini (alkanediyl-alpha,omega-bis(dimethylcetylammonium bromide)) (16
      s-16, s=4, 5, 6) surfactants on the interaction of ninhydrin with chromium
      glycylphenylalanine.
AB  - The effect of gemini (alkanediyl-alpha,omega-bis(dimethylcetylammonium bromide))
      (16-s-16, s=4, 5, 6) surfactants on the interaction of ninhydrin with
      chromium(III) complex of glycylphenylalanine ([Cr(III)-Gly-Phe]2+) has been
      investigated using UV-visible spectrophotometer at different temperatures. The
      order of reaction with respect to [Cr(III)-Gly-Phe]2+ is unity while it is
      fractional with respect to ninhydrin. Whereas, the values of rate constant (kpsi)
      increase and leveling-off regions, like conventional single chain
      cetyltrimethylammonium bromide (CTAB) surfactant, were observed with geminis,
      later produces a third region of increasing kpsi at higher gemini surfactant
      concentrations. This unusual third-region effect of the gemini micelles is
      assigned to changes in their micellar morphologies. The results obtained in
      micellar media were treated in terms of pseudo-phase model. The values of
      thermodynamic parameters (Ea, DeltaH# and DeltaS#) and binding constants (KA and
      KNin) have been evaluated.

PMID- 24878437
TI  - Luminescence studies and EPR investigation of solution combustion derived Eu
      doped ZnO.
AB  - ZnO:Eu (0.1 mol%) nanopowders have been synthesized by auto ignition based low
      temperature solution combustion method. Powder X-ray diffraction (PXRD) patterns
      confirm the nanosized particles which exhibit hexagonal wurtzite structure. The
      crystallite size estimated from Scherrer's formula was found to be in the range
      35-39 nm. Scanning electron microscopy (SEM) and transmission electron microscopy
      (TEM) studies reveal particles are agglomerated with quasi-hexagonal morphology.
      A blue shift of absorption edge with increase in band gap is observed for Eu
      doped ZnO samples. Upon 254 nm excitation, ZnO:Eu nanopowders show peaks in
      regions blue (420-484 nm), green (528 nm) and red (600 nm) which corresponds to
      both Eu2+ and Eu3+ ions. The electron paramagnetic resonance (EPR) spectrum
      exhibits a broad resonance signal at g=4.195 which is attributed to Eu2+ ions.
      Further, EPR and thermoluminescence (TL) studies reveal presence of native
      defects in this phosphor. Using TL glow peaks the trap parameters have been
      evaluated and discussed.

PMID- 24878438
TI  - Vibrational spectra and normal coordinate analysis of 2-hydroxy-3-(2
      methoxyphenoxy) propyl carbamate.
AB  - In this work, the vibrational spectral analysis was carried out by using FT-Raman
      and FTIR spectroscopy in the range 50-4000 cm(-1) and 450-4000 cm(-1)
      respectively, for 2-hydroxy-3-(2-methoxyphenoxy) propyl carbamate (2H3MPPLC)
      molecule. The molecular structure, fundamental vibrational frequencies and
      intensities of the vibrational bands were interpreted with the aid of structure
      optimizations and normal coordinate force field calculations based on density
      functional theory (DFT) and ab initio HF methods with 6-31G(d,p) basis set. The
      complete vibrational assignments of wave numbers were made on the basis of
      potential energy distribution (PED). The results of the calculations were applied
      to simulated spectra of the title compound, which show excellent agreement with
      observed spectra. The scaled B3LYP/6-31G(d,p) results show the best agreement
      with the experimental values over the other method. Stability of the molecule
      arising from hyper conjugative interactions, charge delocalization has been
      analyzed using natural bond orbital (NBO) analysis. The results confirm the
      occurrence of intramolecular charge-transfer (ICT) within the molecule. The
      dipole moment (MU), polarizability (alpha) and hyperpolarizability (beta) of the
      investigated molecule has been computed using B3LYP/6-31G(d,p) method. Mulliken
      population analysis on atomic charges was also calculated. Besides, frontier
      molecular orbitals, molecular electrostatic potential (MEP) and thermodynamic
      properties were performed.

PMID- 24878436
TI  - FT-IR, FT-Raman, molecular structure, first order hyperpolarizability, HOMO and
      LUMO analysis, MEP and NBO analysis of 3-(adamantan-1-yl)-4-(prop-2-en-1-yl)-1H
      1,2,4-triazole-5(4H)-thione, a potential bioactive agent.
AB  - The optimized molecular structure, vibrational frequencies, corresponding
      vibrational assignments of 3-(adamantan-1-yl)-4-(prop-2-en-1-yl)-1H-1,2,4
      triazole-5(4H)-thione have been investigated experimentally and theoretically
      using Gaussian09 software package. Potential energy distribution of normal modes
      vibrations was done using GAR2PED program. The HOMO and LUMO analysis are used to
      determine the charge transfer within the molecule. The stability of the molecule
      arising from hyperconjugative interaction and charge delocalization has been
      analyzed using NBO analysis. The calculated geometrical parameters are in
      agreement with the XRD data. The calculated first hyperpolarizability is high and
      the title compound is an attractive candidate for further studies in nonlinear
      optical applications. To estimate the chemical reactivity of the molecule, the
      molecular electrostatic potential is calculated for the optimized geometry of the
      molecule. 

PMID- 24878439
TI  - Spectrofluorimetric determination of melatonin in kernels of four different
      Pistacia varieties after ultrasound-assisted solid-liquid extraction.
AB  - Melatonin is normally consumed to regulate the body's biological cycle. However
      it also has therapeutic properties, such as anti-tumor, anti-aging and protects
      the immune system. There are some reports on the presence of melatonin in edible
      kernels such as walnuts, but the extraction of melatonin from pistachio kernels
      is reported here for the first time. For this, the methanolic extract of
      pistachio kernels was exposed to gas chromatography/mass spectrometry analysis
      which confirmed the presence of melatonin. A fluorescence-based method was
      applied for the determination of melatonin in different extracts. When excited at
      lambda=275 nm, the fluorescence emission intensity of melatonin was measured at
      lambda=366 nm. Ultrasound-assisted solid-liquid extraction was used for the
      extraction of melatonin from pistachio kernels prior to fluorimetric
      determination. To achieve the highest extraction recovery, the main parameters
      affecting the extraction efficiency such as extracting solvent type and volume,
      temperature, sonication time and pH were evaluated. Under the optimized
      conditions, a linear dependence of fluorescence intensity on melatonin
      concentration was observed in the range of 0.0040-0.160 MUg mL(-1), with a
      detection limit of 0.0036 MUg mL(-1). This method was applied successfully for
      measuring and comparing the melatonin content in the kernels of four different
      varieties of Pistacia including Ahmad Aghaei, Akbari, Kalle Qouchi and Fandoghi.
      In addition, the results obtained were compared with those obtained using GC/MS.
      A good agreement was observed indicating the reliability of the proposed method.

PMID- 24878440
TI  - Synthesis, growth, structural and optical studies of organic nonlinear optical
      material--piperazine-1,4-diium bis 2,4,6-trinitrophenolate.
AB  - Piperazine-1,4-diium bis 2,4,6-trinitrophenolate is one of the useful organic
      materials with nonlinear optical (NLO) and pharmaceutical applications. The
      material was grown by slow evaporation solution growth method at room
      temperature. The crystal system and lattice parameters were identified by single
      crystal XRD analysis. The grown material crystallizes in monoclinic system with
      P21/n space group. The main functional groups NH2, NO2, CN, CC, and phenolic 'O'
      atom were identified using FTIR analysis. The protons and carbons of grown
      crystal with various chemical environments were studied by 1H and 13C NMR
      spectroscopy to confirm the molecular structure. The optical properties of the
      crystal were studied by UV-vis-NIR spectroscopy and the transmission 100% range
      starts from 532 nm onwards. The optical band gap was measured as 2.63 eV from the
      plot of (alphahnu)2 versus hnu. The thermal stability was detected at 304.1
      degrees C using TG-DTA analysis. The dielectric studies of the sample were
      carried out at different temperatures in the frequency range from 50 Hz to 5 MHz
      to establish the dielectric nature of the crystal. Photoconductivity measurements
      were carried out on the grown crystal. The Second Harmonic Generation (SHG) of
      the crystal was tested to confirm the nonlinear optical property.

PMID- 24878441
TI  - Multi-responsive photochromism of a new diarylethene with a salicylaldehyde
      group.
AB  - A new photochromic diarylethene with a salicylaldehyde group was synthesized and
      fully characterized. With the stimulation of acid/base and light, the
      diarylethene showed multi-responsive photochromism. The deprotonated derivative
      of the diarylethene with salicylaldehyde group, due to the addition of
      triethylamine into its solution, also showed excellent photochromism with
      distinguishable color change. And the deprotonated example could recover its
      original state with trifluoroacetic acid. Furthermore, the processes of
      photochromism and acidichromism could be effectively modulated with light and
      chemicals. Cyclic voltammetry tests suggested that triethylamine could
      significantly decrease band-gaps of both open-ring and closed-ring isomers of the
      diarylethene. 

PMID- 24878442
TI  - Application of supervised Kohonen map and counter propagation neural network for
      classification of nucleic acid structures based on their circular dichroism
      spectra.
AB  - One of the most popular instrumental methods to detect the DNA structure is
      circular dichroism. Specific experimental conditions are required to form
      different structures of DNA. However, there is the possibility of different
      structures establishing in the similar circumstance. So, methods development to
      improve the classification and prediction of structures using their spectra
      information are needed. To this end, we applied unsupervised (PCA) and supervised
      (PLS-DA, SKN, and CPNN) approaches to classify CD spectra dataset of different
      DNA sequences (random coil (ss-DNA), duplex, hairpin, reversed and normal
      triplex, parallel and antiparallel G-quadruplex, and i-motif). The main part of
      this work concentrates on the application of artificial neural networks and
      weight analysis to obtain more classification and prediction accuracy. For this
      purpose, the trained network was run 10 times, and the average weights were
      taken. Also, weight analysis was done for the prediction of mixture samples
      include different structures. The results prove that new method of weights
      analysis based on SKN and CPNN is useful for classification of complicated data
      such as different types of DNA structures. 

PMID- 24878443
TI  - Potential food allergens in medications.
AB  - Excipients are substances in pharmaceuticals other than the active ingredients.
      Some excipients are foods or substances derived from foods, raising the
      possibility that these substances would pose a hazard to patients with food
      allergy. This review describes which food-derived substances are used as
      pharmaceutical excipients in which medications and reviews published data
      regarding the safety of the administration of these medications to recipients
      with food allergy. Such reactions are rare, usually because the amount of food
      protein is not present in a large enough quantity to elicit a reaction. When a
      food protein appears as an unintentional contaminant, the amount, if any, that is
      present might be variable and might elicit reactions only from some lots of
      medication or only in some patients. In most circumstances these medications
      should not be routinely withheld from patients who have particular food allergies
      because most will tolerate the medications uneventfully. However, if a particular
      patient has had an apparent allergic reaction to the medication, potential
      allergy to the food component should be investigated. 

PMID- 24878445
TI  - Neurogenic cough.

PMID- 24878446
TI  - IMM-H004, a novel coumarin derivative compound, attenuates the production of
      inflammatory mediatory mediators in lipopolysaccharide-activated BV2 microglia.
AB  - Therapeutic strategies designed to inhibit the activation of microglia may lead
      to significant advancement in the treatment of most neurodegenerative diseases. 7
      hydroxy-5-methoxy-4-methyl-3-(4-methylpiperazin-1-yl)-coumarin (IMM-H004) is a
      novel compound and has been reported exerting potent neuroprotective effects
      which may be related to anti-inflammation. In the present study, the anti
      inflammatory effects of IMM-H004 were investigated in lipopolysaccharide (LPS)
      treated BV2 microglia. Our observations indicated that treatment with IMM-H004
      significantly inhibited BV2 microglia activation, protected PC12 cells and
      primary neurons against indirect toxicity mediated by exposure to conditioned
      medium (CM) from LPS-treated BV2 cells. Additionally, IMM-H004 significantly
      suppressed the release of TNF-alpha, IL-1beta and NO, and suppressed the
      expression of pro-inflammatory mediators and cytokines such as iNOS, COX-2, and
      IL-6 in LPS-stimulated BV2 microglia. The nuclear translocation of NF-kappaB and
      the phosphorylation level of JNK and p38 MAPK pathways were also inhibited by IMM
      H004 in LPS-treated BV2 microglia. Moreover, IMM-H004 also was a strong selective
      OH scavenger whose effect was similar with vitamin C. Overall, our findings
      suggested that IMM-H004 might be a promising therapeutic agent for alleviating
      the progress of neurodegenerative diseases associated with microglia activation. 

PMID- 24878447
TI  - Astrocyte transplantation for spinal cord injury: current status and perspective.
AB  - Spinal cord injury (SCI) often causes incurable neurological dysfunction because
      axonal regeneration in adult spinal cord is rare. Astrocytes are gradually
      recognized as being necessary for the regeneration after SCI as they promote
      axonal growth under both physiological and pathophysiological conditions.
      Heterogeneous populations of astrocytes have been explored for structural and
      functional restoration. The results range from the early variable and modest
      effects of immature astrocyte transplantation to the later significant, but
      controversial, outcomes of glial-restricted precursor (GRP)-derived astrocyte
      (GDA) transplantation. However, the traditional neuron-centric view and the
      concerns about the inhibitory roles of astrocytes after SCI, along with the
      sporadic studies and the lack of a comprehensive review, have led to some
      confusion over the usefulness of astrocytes in SCI. It is the purpose of the
      review to discuss the current status of astrocyte transplantation for SCI based
      on a dialectical view of the context-dependent manner of astrocyte behavior and
      the time-associated characteristics of glial scarring. Critical issues are then
      analyzed to reveal the potential direction of future research. 

PMID- 24878449
TI  - Carbazole-dendrimer-based donor-pi-acceptor type organic dyes for dye-sensitized
      solar cells: effect of the size of the carbazole dendritic donor.
AB  - A series of novel D-pi-A type organic dyes, namely, GnTA (n = 1-4), containing
      carbazole dendrons up to fourth generation as a donor, bithiophene as pi-linkage,
      and cyanoacrylic acid as acceptor were synthesized and characterized for
      applications in dye-sensitized solar cells (DSSCs). The photophysical, thermal,
      electrochemical, and photovoltaic properties of the new dyes as dye sensitizers
      were investigated, and the effects of the carbazole dendritic donors on these
      properties were evaluated. Results demonstrated that increasing the size or
      generation of the carbazole dendritic donor of the dye molecules enhances their
      total light absorption abilities and unluckily reduces the amount of dye uptake
      per unit TiO2 area because of their high molecular volumes. The latter was found
      to have a strong effect on the power conversion efficiency of DSSCs. Importantly,
      electrochemical impedance spectroscopy (EIS) revealed that the size or generation
      of the donor had a significant influence on a charge-transfer resistance for
      electron recombination at the TiO2/electrolyte interface, causing a difference in
      open circuit voltage (Voc) of the solar cells. Among them, dye G1TA containing
      first generation dendron as a donor (having lowest molecular volume) exhibited
      the highest power conversion efficiency of 5.16% (Jsc = 9.89 mA cm(-2), Voc =
      0.72 V, ff = 0.73) under simulated AM 1.5 irradiation (100 mW cm(-2)).

PMID- 24878448
TI  - Genetic diagnosis of autism spectrum disorders: the opportunity and challenge in
      the genomics era.
AB  - A genetic etiology for autism spectrum disorders (ASDs) was first suggested from
      twin studies reported in the 1970s. The identification of gene mutations in
      syndromic ASDs provided evidence to support a genetic cause of ASDs. More
      recently, genome-wide copy number variant and sequence analyses have uncovered a
      list of rare and highly penetrant copy number variants (CNVs) or single
      nucleotide variants (SNVs) associated with ASDs, which has strengthened the claim
      of a genetic etiology for ASDs. Findings from research studies in the genetics of
      ASD now support an important role for molecular diagnostics in the clinical
      genetics evaluation of ASDs. Various molecular diagnostic assays including single
      gene tests, targeted multiple gene panels and copy number analysis should all be
      considered in the clinical genetics evaluation of ASDs. Whole exome sequencing
      could also be considered in selected clinical cases. However, the challenge that
      remains is to determine the causal role of genetic variants identified through
      molecular testing. Variable expressivity, pleiotropic effects and incomplete
      penetrance associated with CNVs and SNVs also present significant challenges for
      genetic counseling and prenatal diagnosis.

PMID- 24878451
TI  - A comparative assessment of adverse event classification in the out-of-hospital
      setting.
AB  - OBJECTIVES: We sought to test reliability of two approaches to classify adverse
      events (AEs) associated with helicopter EMS (HEMS) transport. METHODS: The first
      approach for AE classification involved flight nurses and paramedics (RN/Medics)
      and mid-career emergency physicians (MC-EMPs) independently reviewing 50 randomly
      selected HEMS medical records. The second approach involved RN/Medics and MC-EMPs
      meeting as a group to openly discuss 20 additional medical records and reach
      consensus-based AE decision. We compared all AE decisions to a reference
      criterion based on the decision of three senior emergency physicians (Sr-EMPs).
      We designed a study to detect an improvement in agreement (reliability) from fair
      (kappa = 0.2) to moderate (kappa = 0.5). We calculated sensitivity, specificity,
      percent agreement, and positive and negative predictive values (PPV/NPV).
      RESULTS: For the independent reviews, the Sr-EMP group identified 26 AEs while
      individual clinician reviewers identified between 19 and 50 AEs. Agreement on the
      presence/absence of an AE between Sr-EMPs and three MC-EMPs ranged from kappa =
      0.20 to kappa = 0.25. Agreement between Sr-EMPs and three RN/Medics ranged from
      kappa = 0.11 to kappa = 0.19. For the consensus/open-discussion approach, the Sr
      EMPs identified 13 AEs, the MC-EMP group identified 18 AEs, and RN/medic group
      identified 36 AEs. Agreement between Sr-EMPs and MC-EMP group was (kappa = 0.30
      95%CI -0.12, 0.72), whereas agreement between Sr-EMPs and RN/medic group was
      (kappa = 0.40 95%CI 0.01, 0.79). Agreement between all three groups was fair
      (kappa = 0.33, 95%CI 0.06, 0.66). Percent agreement (58-68%) and NPV (63-76%) was
      moderately dissimilar between clinicians, while sensitivity (25-80%), specificity
      (43-97%), and PPV (48-83%) varied. CONCLUSIONS: We identified a higher level of
      agreement/reliability in AE decisions utilizing a consensus-based approach for
      review rather than independent reviews.

PMID- 24878450
TI  - Guanidino groups greatly enhance the action of antimicrobial peptidomimetics
      against bacterial cytoplasmic membranes.
AB  - Antimicrobial peptides or their synthetic mimics are a promising class of
      potential new antibiotics. Herein we assess the effect of the type of cationic
      side chain (i.e., guanidino vs. amino groups) on the membrane perturbing
      mechanism of antimicrobial alpha-peptide-beta-peptoid chimeras. Langmuir
      monolayers composed of 1,2-dipalmitoyl-sn-glycero-3-phosphatidylglycerol (DPPG)
      were used to model cytoplasmic membranes of both Gram-positive and Gram-negative
      bacteria, while lipopolysaccharide Kdo2-lipid A monolayers were mimicking the
      outer membrane of Gram-negative species. We report the results of the
      measurements using an array of techniques, including high-resolution synchrotron
      surface X-ray scattering, epifluorescence microscopy, and in vitro antimicrobial
      activity to study the molecular mechanisms of peptidomimetic interaction with
      bacterial membranes. We found guanidino group-containing chimeras to exhibit
      greater disruptive activity on DPPG monolayers than the amino group-containing
      analogues. However, this effect was not observed for lipopolysaccharide
      monolayers where the difference was negligible. Furthermore, the addition of the
      nitrobenzoxadiazole fluorophore did not reduce the insertion activity of these
      antimicrobials into both model membrane systems examined, which may be useful for
      future cellular localization studies. 

PMID- 24878452
TI  - The incidence of papillary thyroid carcinoma and outcomes in operative patients
      according to their body mass indices.
AB  - BACKGROUND: The connection between high body mass index (BMI), risk of papillary
      thyroid carcinoma (PTC), and the aggressiveness of PTC is still debated. We aimed
      to establish the relationship between excess BMI and the risk of PTC in an
      operative population, and the impact of obesity on histopathologic aggressiveness
      of PTC and on the outcome of patients. METHODS: All consecutive patients who
      underwent thyroid operation from June 2002 to December 2009 were reviewed in this
      retrospective study. BMI groupings were based on standardized categories: normal
      weight, overweight, and obesity. We performed a total thyroidectomy with lymph
      node dissection in patients with preoperative or operative diagnosis of PTC.
      Radioiodine ablation was performed in every N1 patient, in case of tumor size
      greater than 10 mm, and if there was extrathyroidal invasion. During a median
      follow-up of 6.2 years, patients who were retreated by operation or (131)I were
      considered to have a persistent (<18 months of the initial operative treatment)
      or recurrent (>= 18 months) disease. RESULTS: Of 6,684 patients who had a thyroid
      gland resection, we identified 1,216 (18.2%) patients with PTC. Patients who were
      overweight or obese were not at greater risk of PTC than normal-weight subjects.
      Indications for operation or radioiodine therapy were similar in the three BMI
      groups. During follow-up, 86 patients (7.1%) experienced persistent (4.5%) or
      recurrent (2.5%) disease. When excluding micro-PTCs (<= 10 mm), we found an
      association between recurrent or residual locoregional thyroid cancer and BMI:
      18.7% in obese patients versus 8.5% if BMI <25 kg/m(2) and 9.8% if 25 >= BMI < 30
      kg/m(2) (P = .03). This difference was clearly marked for persistence. When
      adjusted for other cofounder factors, we observed that BMI was an independent
      factor associated with the risk of postoperative locoregional event (odds ratio
      3.8, 95% confidence interval 1.6-8.8), with sex, age, lymph node metastasis, and
      tumor bilaterality. CONCLUSION: In macro-PTC, obese patients had an increased
      risk of developing a locoregional event during the follow-up, specifically a
      persistence of the disease. According to these results, overweight and obese
      patients with macro-PTC should be monitored more carefully for early detection of
      cancer persistence.

PMID- 24878453
TI  - A prospective comparison of patient body image after robotic thyroidectomy and
      conventional open thyroidectomy in patients with papillary thyroid carcinoma.
AB  - BACKGROUND: Body image is associated with self-esteem and identity and has a
      close relationship with quality of life (QoL). We compared the impact of surgical
      scars on the patient's perception of body image between conventional open
      thyroidectomy (OT) and robotic thyroidectomy (RT) in female papillary thyroid
      carcinoma patients. METHODS: From October 2009 to December 2010, we enrolled
      prospectively 116 papillary thyroid carcinoma patients who underwent total
      thyroidectomy at the Yonsei University Health System (Seoul, Korea). Of these 116
      patients, 56 had OT and 60 RT. Their scars were assessed using the Vancouver Scar
      Scale (VSS), and psychometric properties were evaluated using the Body Image
      Scale (BIS) questionnaire postoperatively. Both groups were compared using cross
      sectional and time-series methods. RESULTS: Mean age was significantly younger in
      the RT group. Regarding scar quality, the OT group showed superiority in scar
      pigmentation and the total VSS score during the early postoperative period, but
      the VSS score improved over time and was similar between both groups at 9 months.
      The RT group had better scores regarding most of the BIS items, a trend that
      remained relatively constant over time. In patients with noticeable scars (VSS >=
      2) at 9 months, the RT group had better BIS scores regarding almost all items,
      including "self-conscious," "physical attractiveness," "feeling of less
      feminine," "sexual attractiveness," "dissatisfaction with body, scar and
      appearance when dressed," and "avoidance of people due to appearance."
      CONCLUSION: RT provides a better self-body image and improves QoL compared with
      conventional OT by avoiding a noticeable cervical scar.

PMID- 24878454
TI  - Commentary on: a prospective comparison of patient body image after robotic
      thyroidectomy and conventional open thyroidectomy in patients with papillary
      thyroid carcinoma.

PMID- 24878455
TI  - A systematic review and meta-analysis of the clinicopathologic characteristics of
      cystic versus solid pancreatic neuroendocrine neoplasms.
AB  - INTRODUCTION: Cystic pancreatic neuroendocrine neoplasms (PNENs) are rare
      neoplasms, and presently, it is uncertain whether their behavior is similar or
      distinct from their solid counterparts. This study aimed to review systematically
      the present literature to compare the clinicopathologic characteristics of cystic
      PNENs versus their solid counterparts to determine whether cystic PNENs are
      likely to be a distinct entity from solid PNENs. METHODS: Comparative studies of
      solid versus cystic PNENs studies were reviewed. Cystic and solid PNENs were
      compared on the basis of several clinicopathologic characteristics. RESULTS:
      Seven nonrandomized case control studies compared 152 cystic versus 915 solid
      PNENs. Pooled analysis demonstrated that the likelihood of PNENs to be located in
      the head/uncinate of the pancreas was lower for cystic than solid neoplasms
      (27.7% vs 45.5%, odds ratio [OR] 0.452, 95% confidence interval [95% CI] 0.304
      0.673, P < .001). Cystic PNENs were less likely to be functional (14% vs 24.4%,
      OR 0.405, 95% CI 0.221-0.742, P = .003) and were more likely to be
      benign/uncertain rather than malignant compared with solid PNENs (90.3% vs 65.9%,
      OR 3.151, 95% CI 1.297-7.652, P = .011). Cystic PNENs were more likely to have a
      mitotic count <2 per 10 hpf and a Ki67 index <2% (93.3% vs 72.7%, OR 4.897, 95%
      CI 2.139-11.209, P < .001 and 82.4% vs 54.1%, OR 4.079, 95% CI 2.177-7.641, P <
      .001), respectively. Cystic neoplasms were also less likely to have regional
      lymph node metastases than solid neoplasms (11.2% vs 28.9%, OR 0.387, 95% CI
      0.219-0.685, P = .001).In this meta-analysis, there was no difference in the 5
      year overall survival and 5-year disease-free survival between cystic vs solid
      PNENs (92.0% vs 86.8%, P .214) and (98.1% vs 83.9%, P = .185). CONCLUSION: These
      findings suggest that cystic PNENs tend to be biologically less aggressive
      compared with their solid counterparts; more data, however, with respect to
      molecular analysis are required to establish whether cystic and solid PNENs were
      distinct pathologic entities.

PMID- 24878456
TI  - The influence of contemporaneous revascularization on biliary complications after
      liver transplantation.

PMID- 24878457
TI  - Impact of a randomized clinical trial on children with perforated appendicitis.
AB  - BACKGROUND: We previously conducted a randomized, clinical trial comparing early
      appendectomy with interval appendectomy for perforated appendicitis. The purpose
      of the present study was to evaluate the effect this clinical trial had on
      subsequent practice patterns and outcomes for patients with perforated
      appendicitis at the free-standing children's hospital conducting the trial.
      METHODS: A retrospective study was conducted comparing children with perforated
      appendicitis treated before the trial (2005-2006) and after the trial (2009
      2011). Early appendectomy was performed within 24 hours of diagnosis; interval
      appendectomy occurred 4-6 weeks after initial treatment with antibiotics. Patient
      characteristics, treatment variables, and outcomes were collected and compared.
      RESULTS: The pretrial group consisted of 92 patients-62 (67%) underwent early
      appendectomy, and 30 (33%) patients had interval appendectomy. The posttrial
      group was composed of 103 patients, with 87 (84%) undergoing early appendectomy
      and 16 (16%) interval appendectomy (P = .005). The groups were similar in patient
      and admission characteristics, although the posttrial group had a lower
      percentage of self-pay patients and fewer computed tomography scans; health care
      use was similar between groups. Overall, the posttrial group had fewer adverse
      events (18% vs 34%, P = .02), specifically fewer wound infections (2% vs 14%, P =
      .001) and fewer unplanned readmissions (7% vs 16%, P = .04) than the pretrial
      group. In the posttrial group, those patients selected for interval appendectomy
      were more likely to complete the planned course of therapy than in the pretrial
      group. CONCLUSION: A clinical trial conducted at our institution to evaluate
      currently available treatment options for perforated appendicitis did change
      practice patterns at our hospital. After the trial, there was an increase in the
      use of early appendectomy, a decrease in the number of computed tomography scans
      performed per patient, and a reduction in the overall adverse event rate.

PMID- 24878458
TI  - The impact of nodal status on outcome in older patients with papillary thyroid
      cancer.
AB  - BACKGROUND: The impact of clinically or radiologically detected nodal metastases
      on survival in patients with papillary thyroid cancer (PTC) is controversial but
      seems more important and relevant in older patients. The objective of this study
      was to determine the impact of clinically or radiologically detected nodal
      metastases on outcome in patients 45 years of age or older. METHODS:
      Retrospective analysis of 834 patients 45 years or older who underwent operation
      for PTC between 1986 and 2005. RESULTS: With a median follow up of 77 months, the
      5 year disease-specific survival (DSS) and recurrence-free survival (RFS) were
      99% and 94%, respectively. Patients with clinically N+ nodes with pathologic
      confirmation were stratified into pN0/Nx, pN1a, and pN1b, respectively. Five-year
      DSS was 100%, 100%, and 91% for pN0/Nx, pN1a, and pN1b disease; P < .001.
      Patients with pN1b disease had poorer distant RFS compared with pN0/Nx and pN1a
      patients (84%, 99%, and 99%; P < .001). The presence of pN1b disease was an
      independent predictor of worse DSS and distant RFS on multivariate analysis,
      conferring a 10-fold increased risk of distant metastases and death. All cause
      specific deaths were due to distant metastases. CONCLUSION: Older patients with
      PTC and N1b disease at presentation have poorer DSS compared with patients with
      pN0/Nx or N1a disease. The cause of death in these patients is due to distant
      metastases rather than locoregional recurrence.

PMID- 24878459
TI  - Commentary on: a prospective comparison of patient body image after robotic
      thyroidectomy and conventional open thyroidectomy in patients with papillary
      thyroid carcinoma.

PMID- 24878460
TI  - What Test is Needed to Discontinue Medications after Successful Epilepsy Surgery?

PMID- 24878461
TI  - Head Injury in the Elderly: Is Our Health Care System Ready for the Fall(s)?

PMID- 24878462
TI  - Prognostic tests and antiepileptic drug withdrawal after epilepsy surgery.
AB  - Approximately one in three patients with a successful epilepsy surgery will have
      seizure recurrence following antiepileptic drugs (AED) withdrawal. The value of
      postoperative testing for predicting seizure relapse after AED tapering is not
      clear. The purpose of this study was to review the literature for evidence on the
      use of postoperative investigations before AED discontinuation after successful
      epilepsy surgery. We were unable to identify studies on the prognostic value of
      postoperative magnetic resonance imaging and AED blood levels. The literature
      review yielded seven studies on the predictive value of electroencephalography.
      Four studies found no association between interictal discharges (IED) and seizure
      relapse. These studies suffered from various limitations due to their
      retrospective design and generally small cohorts. Two of the three studies
      reporting a positive association were prospective and provided strong evidence of
      an increased risk of seizure recurrence with presence of postoperative IED in
      successfully operated patients undergoing AED withdrawal. 

PMID- 24878463
TI  - Canadian epileptologists' counseling of drivers amidst guideline inconsistencies.
AB  - BACKGROUND: Epilepsy is a common medical condition for which physicians perform
      driver fitness assessments. The Canadian Medical association (CMA) and the
      Canadian Council of Motor transportation administrators (CCMTA) publish documents
      to guide Canadian physicians' driver fitness assessments. OBJECTIVES: We aimed to
      measure the consistency of driver fitness counseling among epileptologists in
      Canada, and to determine whether inconsistencies between national guidelines are
      associated with greater variability in counseling instructions. METHODS: We
      surveyed 35 epileptologists in Canada (response rate 71%) using a questionnaire
      that explored physicians' philosophies about driver fitness assessments and
      counseling practices of seizure patients in common clinical scenarios. Of the
      nine scenarios, CCMTA and CMA recommendations were concordant for only two.
      Cumulative agreement for all scenarios was calculated using Kappa statistic.
      Agreement for concordant (two) vs. discordant (seven) scenarios were split at the
      median and analyzed using the Wilcoxon signed rank sum test. RESULTS: Overall the
      agreement between respondents for the clinical scenarios was not acceptable
      (Kappa=0.28). For the two scenarios where CMa and CCMta guidelines were
      concordant, specialists had high levels of agreement with recommendations (89%
      each). A majority of specialists disagreed with CMa recommendations in three of
      seven discordant scenarios. The lack of consistency in respondents' agreement
      attained statistical significance (p<0.001). CONCLUSIONS: Canadian
      epileptologists have variable counseling practices about driving, and this may be
      attributable to inconsistencies between CMa and CCMta medical fitness guidelines.
      This study highlights the need to harmonize driving recommendations in order to
      prevent physician and patient confusion about driving fitness in Canada.

PMID- 24878465
TI  - A Unique Model for ONSD Part II: Inter/Intra-operator Variability.
AB  - OBJECTIVE: To evauluate our novel ultrasound model for measurement of optic nerve
      sheath diameter (ONSD) and determine the intra- and inter-operator variability
      associated with this technique. METHODS: We conducted ten measurements of ONSD
      per model amongst eight different models with a single experienced operator to
      examine intra-operator variability. Similarly, we had seven different operators
      measure the OSND twice in eight different models, in order to determine inter
      operator variability analyzed with a three level linear statistical model.
      RESULTS: For intra-operator variability, the intra-cluster correlation
      coefficients for the experienced and novice operators were 0.643 and 0.453
      respectively. This displayed improvement in intra-operator variability with
      experience. The inter-cluster correlation coefficient was 0 for the group of
      novice operators, indicating negligible difference amongst multiple operators in
      measuring any given model of ONSD. A strong, statistically significant, linear
      relationship between the actual model disc size and the ultrasound ONSD measures
      was identified, implying the reliability of the images produced by our novel
      model. CONCLUSIONS: Utilizing a novel model for ONSD ultrasonography, we have
      determined the intraoperator reliability of ONSD measurement to be moderate, with
      no appreciable difference amongst multiple operators. Improvement in measurement
      reliability has been demonstrated between expert and novice operators with our
      model, indicating the potential benefit of simulation platforms for teaching the
      technique of ONSD ultrasound.

PMID- 24878464
TI  - Neurophobia inception: a study of trainees' perceptions of neurology education.
AB  - OBJECTIVES: We wanted to examine the extent to which "neurophobia" exists among
      medical students and determine if students' perceptions of neurology differ by
      year of study while exploring the factors that contribute to the development of
      "neurophobia". METHODS: We used a two-phase, sequential, mixed-methods
      explanatory design in this single centre study. Phase 1 involved the collection
      and analysis of a questionnaire administered to students in the first three years
      of medical school. Phase 2 involved focus groups of a subgroup of students who
      demonstrated evidence of neurophobia in Phase 1. RESULTS: In total, 187 (39 %)
      undergraduate medical trainees responded to the questionnaire (response rates of
      37%, 44% and 19% for first-, second- and third-year students, respectively). 24%
      of respondents indicated that they were afraid of clinical neurology and 32% were
      afraid of the academic neurosciences. Additionally, 46% of respondents thought
      that clinical neurology is one of the most difficult disciplines in medicine.
      Phase 2 findings revealed that many students reported negative preconceptions
      about neurology and commented on neurology's difficulty. Some experienced changes
      in these conceptions following their neurology block. Past clinical, educational,
      and personal experiences in neurology impacted their comfort level. CONCLUSIONS:
      This study shows that the level of comfort towards clinical neurology increases
      following students' participation in second-year neurology blocks, but that third
      year students continue to show signs of neurophobia with lower comfort levels. It
      provides insight into why neurophobia exists amongst medical students and sheds
      light on pre-existing and emerging factors contributing to this sense of
      neurophobia.

PMID- 24878466
TI  - Hospitalized head and spine injuries on Saskatchewan farms.
AB  - INTRODUCTION: With over 44,000 individual farms, farm dwellers account for 11% of
      the population of Saskatchewan. There is limited data on brain and spine injuries
      acquired on farms. The objective of this study was to evaluate the epidemiology
      of head and spine injuries on Saskatchewan farms to assist the development of
      injury prevention initiatives. METHODS: Using the Canadian Centre for
      Agricultural Health and Safety's Saskatchewan Farm Injury Surveillance Database,
      farm-related head and spine injuries hospitalized > 24 hours were examined (1990
      2007). We collected information regarding the type and mechanism of injury as
      well as the geographic location of both the injury and treatment. RESULTS: The
      database captured 390 brain injuries and 228 spine injuries, including 16 spinal
      cord injuries. The majority of patients were male (73.3% of head injuries and
      84.2% of spine injuries). The highest risk age groups were 50-59 years, with
      24.1% of the spine injuries, and 40-49 years, with 19.2% of the head injuries.
      The most common causes of injury were falls and/or machinery-related. The average
      annual incidence of farm-related spine and head injury were 10.8 and 17.6 per
      100,000 farm population, respectively. All patients included in this study were
      hospitalized for over 24 hours, with 44.7% of spine injuries spending over one
      week in hospital, and 20% of head injuries spending over three days in hospital.
      CONCLUSIONS: Injury prevention initiatives should be targeted towards males aged
      40-59 years residing in the southern areas of the province, with increased
      awareness towards the dangers of falls and operating tractors.

PMID- 24878467
TI  - Chemotherapy-induced Peripheral Neuropathy Among Paediatric Oncology Patients.
AB  - BACKGROUND: Vinca alkaloids and platinum-containing chemotherapeutic drugs have
      the potential to cause chemotherapy-induced peripheral neuropathy (CIPN). This
      study determined the frequency of CIPN among children who were treated for acute
      lymphoblastic leukemia (ALL), lymphoma, brain tumour or Wilms tumour. PROCEDURE:
      This retrospective cohort study reviewed 252 patients treated at the Children's
      hospital of Eastern Ontario from 2001-2011. Patients were considered to have CIPN
      if they developed clinical symptoms of CIPN such as limb paraesthesia, weakness
      and/or ataxia during chemotherapy and their treating neurologist or oncologist
      deemed that their symptoms were due to a peripheral cause. Patients were excluded
      if their treatment regime did not include chemotherapy. RESULTS: The overall
      frequency of CIPN was 18.3% (46/252). Tumour-specific CIPN rates were: 18.9%
      (29/154) for ALL; 9.4% (3/32) for lymphoma; 17.9% (5/28) for Wilms tumour; and
      23.7% (9/38) for brain tumour patients. Nerve conduction studies were completed
      for 17% of patients (all tumour types) and were abnormal in all but one patient.
      Among surviving CIPN patients (41/46), 93% showed no clinical deficits at their
      last examination, which was on average 56 months from time of diagnosis to last
      follow-up visit. CONCLUSIONS: The frequency of CIPN was less than that previously
      reported in adults receiving chemotherapy. Children with CIPN have a favourable
      outcome with most showing clinical improvement during the maintenance phase of
      treatment or after chemotherapy completion.

PMID- 24878468
TI  - HOXA1 Mutations are Not Commonly Associated with Non-Syndromic Deafness.
AB  - OBJECTIVE: Homozygous homeobox A1 (HOXA1) mutations cause a spectrum of
      abnormalities in humans including bilateral profound deafness. This study
      evaluates the possible role of HOXA1 mutations in familial, non-syndromic
      sensorineural deafness. METHODS: Forty-eight unrelated Middle Eastern families
      with either consanguinity or familial deafness were identified in a large
      deafness clinic, and the proband from each family was evaluated by chart review,
      audiogram, neuroimaging, and HOXA1 sequencing. RESULTS: All 48 probands had
      normal neuro-ophthalmologic and general medical examinations except for
      refractive errors. All had congenital non-syndromic sensorineural hearing loss
      that was symmetric bilaterally and profound (>90 dBHL) in 33 individuals and
      varied from 40 to 90 dBHL in the remainder. Thirty-nine of these individuals had
      neuroimaging studies, all documenting normal internal carotid arteries and normal
      6th, 7th, and 8th cranial nerves bilaterally. Of these, 27 had normal internal
      ear structures with the remaining 12 having mild to modest developmental
      abnormalities of the cochlea, semicircular canals, and/or vestibular aqueduct. No
      patient had homozygous HOXA1 mutations. CONCLUSIONS: None of these patients with
      non-syndromic deafness had HOXA1 mutations. None had major inner ear anomalies,
      obvious cerebrovascular defects, or recognized congenital heart disease. HOXA1 is
      likely not a common cause of non-syndromic deafness in this Middle Eastern
      population.

PMID- 24878469
TI  - Neurocognitive changes in tertiary neurosyphilis: a retrospective chart review.
AB  - CONTEXT: Since the beginning of the new millennium, prevalence of syphilis has re
      increased and is once again, a major public health problem. Neurosyphilis is the
      extension of syphilitic infection to the nervous system. It is considered by many
      as a cause of reversible dementia, when treated early. However, scarce data exist
      on the evolution of cognitive and behavioral impairments in patients affected by
      tertiary neurosyphilis. OBJECTIVES: The aim of this study was to explore the
      cognitive and behavioral changes in a cohort of patients diagnosed with
      neurosyphilis. DESIGN: A retrospective study based on systematized chart review
      between 2000 and 2012 in a large neurological tertiary care facility. OUTCOME
      MEASURE: Clinical evaluations by treating physicians. RESULTS: Eighteen patients
      were identified with tertiary neurosyphilis. Out of this group, only two had
      systematic neuropsychological follow-up despite physician reports of significant
      and persistent cognitive and psychiatric changes. For these two cases, only
      slight improvements were noted in memory and executive skills while improvements
      in attention were marked. None of our patients had previous psychiatric history
      yet a large proportion developed symptoms after the infection. CONCLUSION:
      Although neurosyphilis is traditionally considered a reversible form of dementia,
      we found limited support for this claim in our two patients with close follow-up.
      Quality data on the cognitive and psychiatric changes in the rest of our cohort
      was dramatically lacking, and this could not be explained by absence of symptoms
      at presentation. Given the recrudescence of syphilis, we propose a systematic
      approach to the evaluation and follow-up of this disorder.

PMID- 24878470
TI  - The effects of Vitamin D Insufficiency and Seasonal Decrease on cognition.
AB  - BACKGROUND: Vitamin D3 (cholecalciferol) deficiency has been associated with
      dementia and cognitive decline. Which cognitive domains are most associated with
      D3 levels and how seasonal fluctuations in levels relate to cognition is unclear.
      We addressed these questions using a prospective observational study examining
      associations between D3 levels and cognition among individuals living in northern
      latitudes (54 degrees N) in summer and winter. METHODS: Healthy adult
      participants underwent testing in summer and winter of D3 levels and cognition,
      using the Symbol digit Modalities test, phonemic fluency, digit Span and CANTAB
      battery. RESULTS: Of 32 participants tested in the summer, 46% were D3
      insufficient (<75 nmol/L) and performed worse on digit Span Backward (DS-B)
      (MU=5.8, SD=2) than those who were sufficient (MU=7.9, SD=2), p=0.018. In
      multivariate analyses, sufficiency status was an independent predictor of dS-B,
      (b=0.41, p=0.02). The majority (63%) of 19 participants tested in winter were D3
      insufficient, with levels declining by a median of 15 nmol/L overall. Those with
      insufficient levels performed worse (i.e., higher scores) on the CANTAB Spatial
      Working Memory (SWM) task (MU=36.1, SD=6 versus MU=29.3, SD=8), p=0.05). Those
      with larger drops in levels (>=15 nmol/L) showed decline/less improvement on the
      CANTAB one touch Stockings of Cambridge (OTS) task, (MU=0.50, SD=1.9 versus MU=
      2.11, SD=2.6, p=0.01), a test of working memory/executive functioning.
      CONCLUSIONS: Vitamin D3 insufficiency and seasonal declines >=15 nmol/L were
      associated with inferior working memory/executive functioning. While our findings
      require confirmation, they suggest that sufficient D3 levels should be maintained
      year-round, likely necessitating supplementation, at least during winter at
      higher latitudes.

PMID- 24878471
TI  - Trends in Hospitalization Associated with TBI in an Urban Level 1 Trauma Centre.
AB  - OBJECTIVE: Traumatic brain injury (TBI) is the single largest cause of death and
      disability following injury worldwide. The aim of this study was to determine the
      demographic, clinical, medical and accident related trends for patients with TBI
      hospitalized in an urban level 1 Trauma Centre. METHODS: Data were
      retrospectively collected on individuals (n = 5,642) who were admitted to the
      Traumatic Brain Injury Program of the McGill University Health Centre - Montreal
      General Hospital from 2000 to 2011. RESULTS: Regression analysis showed a
      significant upward trend in the yearly number of cases as well as an upward
      trending by year in the proportion of TBI cases aged 70-years-old or more. The
      Injury Severity Scale scores were positively associated with year indicating a
      slight increase in injury severity over the years and there was an increase in
      patient psychological, social and medical premorbid complexity. In addition, the
      Extended Glasgow Outcome Scale score tended to become more severe over the years.
      There was a slight decrease in the proportion of discharges home and in the
      proportion of deaths. CONCLUSIONS: These results will help to understand the
      impact of TBI in an urban Canadian level 1 Trauma Centre. This information should
      be used to develop public prevention strategies and to educate the community
      about the risk of TBI especially the risk of falls in the ageing population.
      These findings can also provide information to help health policy makers plan for
      future resources.

PMID- 24878472
TI  - Endoscopic third ventriculostomy for hydrocephalus due to tectal glioma.
AB  - BACKGROUND: Tectal gliomas commonly present with hydrocephalus from obstruction
      of the aqueduct of Sylvius. The creation of a ventriculostomy in the floor of the
      third ventricle (ETV) has been previously reported to by-pass aqueduct
      obstruction. The goal of this study was to determine the safety and efficacy of
      ETV in the presence of an obstructing tectal glioma. METHODS: We retrospectively
      reviewed the clinical presentation, management, and clinical outcome after ETV in
      patients diagnosed with tectal glioma and obstructive hydrocephalus in our
      institution over a period of 15 years. Shunt freedom at follow-up was the main
      outcome variable. Long-term clinical outcome was assessed at the most recent
      clinic visit. Clinical outcome was ranked as excellent, good, or poor according
      to resolution of symptoms and patient functional status. RESULTS: The median age
      at presentation was 16.5 years (range: 6.4 to 59 years) and the most common
      presenting symptom was headache. Eleven patients had ETV as a primary procedure
      and three patients underwent ETV as a substitute for shunt revision at the time
      of shunt failure. At follow-up (median 3.9 years, range: 2.2 to 7 years) 13 of 14
      patients remain shunt independent with excellent (n=9) or good outcomes (n=5).
      CONCLUSIONS: In patients with tectal glioma causing obstructive hydrocephalus,
      ETV can be performed safely in the primary setting or as a substitute for shunt
      revision. A high rate of shunt freedom (78%-100%) at prolonged follow-up can be
      expected in this patient population.

PMID- 24878474
TI  - Impact of glucose fluctuation on acute cerebral infarction in type 2 diabetes.
AB  - OBJECTIVE: This study aimed to describe the frequency and temporal profile of
      acute cerebral infarction (ACI) using a continuous glucose monitoring system
      (CGMS) in patients with and without type 2 diabetes mellitus (T2DM) and explore
      the impact of blood glucose fluctuations on the short-term prognosis of ACI.
      METHODS: The subjects were divided into four groups: T2DM with acute cerebral
      infarction (DMCI, Group A, n=56); T2DM without acute cerebral infarction (DM-NCI,
      Group B, n=36); Acute cerebral infarction patients without T2DM (NDM-CI, Group C,
      n=54); Healthy control group (NG, Group D, n=36). The National Institutes of
      Health Stoke Scale (NIHSS) and modified Rankin scale (mRs) were collected in
      Group A and C. All subjects were monitored for 72 hours using the CGMS. Indices
      such as fasting blood glucose (FBG) and mean amplitude of glycemic excursions
      (MAGE) were calculated. Glycemic excursions were compared between Group A, B, C
      and Group D, respectively. Multiple linear regression analysis and logistic
      analysis was applied. RESULTS: MAGE is related to NIHSS, homocysteine (HCY), HOMA
      IR, FBG, CRP and IMT, while NIHSS is related to CRP, HCY, HOMA-IR, IMT. The
      factors impacting the short-term prognosis of ACI were NIHSS, HBA1C and MAGE.
      CONCLUSION: Larger glucose fluctuations are associated with more stroke risk
      factors and are associated with a poorer short-term prognosis. More attention
      should be paid to glucose fluctuations in patients with ACI and a history of
      T2DM.

PMID- 24878473
TI  - The Effect of tPA on Inpatient Rehabilitation after Stroke: A Cost Comparison.
AB  - BACKGROUND: Tissue plasminogen activator has been found to significantly improve
      patient outcomes post stroke. Previous economic evaluations have adjusted for
      fewer admissions to inpatient rehabilitation but not for decreased length of stay
      in rehabilitation. Our objective was to estimate the potential cost savings
      associated with a decreased length of stay in inpatient rehabilitation for
      patients who receive tissue plasminogen activator compared to those who do not,
      in a Canadian context. METHODS: Decreased length of stay in inpatient
      rehabilitation for patients who received tissue plasminogen activator compared to
      controls was reported previously in a population of 1962 patients admitted to
      hospital with an ischemic stroke in Ontario between July 1, 2003 and March 31,
      2008. Average per diem cost savings associated with the use of tissue plasminogen
      activator were calculated using a literature based cost estimate. Sensitivity
      analysis varying the length of stay in inpatient rehabilitation was performed.
      RESULTS: The estimated mean per diem cost of inpatient rehabilitation derived
      from the literature was $626. Based on previously reported estimates for reduced
      length of stay, receipt of tissue plasminogen activator was estimated to result
      in savings of $939 per patient during inpatient rehabilitation. Sensitivity
      analysis suggested that these cost savings could range from $501 to $1377 per
      patient on average. CONCLUSIONS: Future economic evaluations of tissue
      plasminogen activator should consider adjusting for shortened length of stay in
      inpatient rehabilitation for patients who receive tissue plasminogen activator.

PMID- 24878475
TI  - A Chinese patient with pusher syndrome and unilateral spatial neglect syndrome.
AB  - OBJECTIVE: To observe clinical manifestations, behavioral characteristics, and
      effects of rehabilitation on a patient with pusher syndrome and unilateral
      spatial neglect caused by right thalamic hemorrhage. METHODS: Assessment of
      pusher syndrome was made by the Scale for Contraversive pushing (SCP), and
      unilateral spatial neglect syndrome was diagnosed using line cancellation, letter
      and star cancellation, line bisection tests and copy and continuation of graphic
      sequence test. Behavioral therapy, occupational therapy, reading training and
      traditional Chinese medicine methods were adopted for treatment of pusher
      syndrome and unilateral spatial neglect. RESULTS: The patient showed typical
      pusher syndrome and unilateral spatial neglect symptoms. The pusher syndrome and
      unilateral spatial neglect symptoms were significantly improved following
      rehabilitation treatments. CONCLUSIONS: Pusher syndrome and unilateral spatial
      neglect syndrome occurred simultaneously after right thalamic hemorrhage. Early
      rehabilitation therapy can reduce the symptoms of pusher syndrome and unilateral
      spatial neglect syndrome and improve motor function.

PMID- 24878476
TI  - Expression of Urotensin II During Focal Cerebral Ischemic in Diabetic Rats.
AB  - BACKGROUND: The objective of this study was to explore the expression of
      urotensin II (UII), its receptor (GPR14), and vascular endothelial growth factor
      (VEGF), as well as their associations in the ischaemic brains of rats with focal
      cerebral ischaemia, under normal and diabetic conditions. METHODS: Diabetes
      mellitus (DM) was induced by injection of streptozotocin (STZ) into Sprague -
      Dawley rats. Focal cerebral ischaemia was induced by middle cerebral artery
      occlusion (MCAO) four weeks after DM onset by STZ. Rats (n=80) were divided into
      four groups: normal control, DM, MCAO, and DM/MCAO. Immunohistochemistry and
      reverse-transcriptase-polymerase chain reaction (RT-PCR) were used to detect the
      expression of UII, GPR14 and VEGF in the diabetic and ischaemic brain. RESULTS:
      Expression of UII and GPR14 was increased at mRNA and protein levels in the DM
      and MCAO group compared with controls. In the DM/MCAO group, expression of UII
      and GPR14 was increased significantly in the ischaemic brain, and was accompanied
      by a significantly increased VEGF expression. CONCLUSION: Diabetes mellitus was
      seen to aggravate brain lesions after ischaemia, and UII may have an important
      role.

PMID- 24878477
TI  - Reversible splenial lesion following rapid withdrawal of carbamazepine.

PMID- 24878478
TI  - Subdural hematoma: a rare presentation of a convexity meningioma.

PMID- 24878479
TI  - An 18 alanine repeat in a severe form of oculopharyngeal muscular dystrophy.

PMID- 24878480
TI  - Familial cerebral amyloid angiopathy due to the Iowa mutation in an Irish family.

PMID- 24878481
TI  - Niemann Pick C: first case in a Canadian Nakoda Nation child.

PMID- 24878482
TI  - Moyamoya Syndrome Associated with Mucolipidosis-II.

PMID- 24878483
TI  - Screening for depression in a tertiary epilepsy clinic.

PMID- 24878484
TI  - Emergence of Primary CNS Lymphoma in a Patient with Findings of CLIPPERS.

PMID- 24878485
TI  - Reversibility of MRI features of pseudotumor cerebri syndrome.

PMID- 24878486
TI  - Spontaneous cervical spinal epidural hematoma mimicking acute stroke.

PMID- 24878487
TI  - Confusion in giant cell arteritis - a diagnostic challenge.

PMID- 24878488
TI  - Professor Barry N. Rewcastle (1931-2014).

PMID- 24878489
TI  - A generous exchange "from senior, to junior": remembering Dr. Charles Drake.

PMID- 24878490
TI  - "Magic Google in my Hand, Who is the Sickest in my Land?".

PMID- 24878491
TI  - Formal and informal care costs of hospitalized older people at risk of poor
      functioning: A prospective cohort study.
AB  - Hospitalized older people are at risk of poor functioning after hospital
      discharge. We aimed to relate formal and informal care costs to level of risk for
      low functioning of hospitalized older people up to one year after admission. We
      studied 460 patients 65 years or older who were admitted to a 450-bed hospital in
      the Netherlands between June 2010 and October 2010. Participants were classified
      into five risk groups at hospital admission using the Identification Seniors At
      Risk-Hospitalized Patients (ISAR-HP). Patients were interviewed at hospital
      admission and at three and twelve months after admission using validated
      questionnaires to measure health care utilization. Informal caregivers were
      interviewed by mailed paper questionnaires at the same time as patients. We
      estimated costs per unit from hospital information systems and nationally
      representative research. Mean healthcare costs were ?30k euro per person per
      year, with one third for initial hospital stay (?9,8k), one third for formal
      healthcare costs between hospital discharge and twelve month follow up (?10,3k),
      and one third for informal healthcare costs between hospital discharge and twelve
      month follow up (?9,5k). Informal and formal healthcare costs were almost double
      for people with the highest risk score compared to people not at risk (p<0.001).
      Older patients with high risk scores at hospital admission have substantially
      higher formal and informal care costs in the year after initial hospital
      admission than people with low risk scores. This implies that substantial
      investments may be made in preventive interventions for at-risk hospitalized
      older people. 

PMID- 24878492
TI  - Serum and intraocular concentrations of erythropoietin and vascular endothelial
      growth factor in patients with type 2 diabetes and proliferative retinopathy.
AB  - AIM: This study compared systemic and intraocular concentrations of
      erythropoietin (EPO) and vascular endothelial growth factor (VEGF) in patients
      with type 2 diabetes (T2D) and proliferative diabetic retinopathy (PDR) with
      levels in patients without diabetes, and looked for possible correlations between
      the concentrations found and other variables analyzed. METHODS: Concentrations of
      EPO and VEGF were measured in the aqueous and vitreous humours and serum of
      patients undergoing vitrectomy for PDR (33 patients) or for macular holes or
      puckers (20 control patients). EPO was assayed by radioimmunoassay, with a lower
      limit of detection (LOD) of 1.0 mIU/mL. VEGF was assayed using enzyme-linked
      immunosorbent assay (ELISA), with a lower LOD of 10.0 pg/mL. RESULTS: EPO
      concentrations in serum did not differ significantly between the two groups,
      whereas EPO in vitreous and aqueous were higher in diabetic than in non-diabetic
      patients. VEGF in serum was lower in diabetic patients than in non-diabetics;
      conversely, VEGF concentrations in vitreous were significantly higher in diabetic
      patients. A direct correlation was found between vitreous and aqueous EPO
      concentrations, and between vitreous EPO and blood glucose concentrations. A
      significant, negative correlation between vitreous EPO concentration and age was
      also recorded. CONCLUSION: High EPO concentrations in the vitreous of patients
      with PDR and its correlation with blood glucose suggest that EPO could play a
      role in the pathogenesis of PDR. All possible factors affecting serum and ocular
      concentrations of EPO and VEGF should be determined to identify compounds able to
      prevent and control this serious microvascular complication of diabetes.

PMID- 24878493
TI  - Identification of fxyd genes from the spotted scat (Scatophagus argus): molecular
      cloning, tissue-specific expression, and response to acute hyposaline stress.
AB  - By interacting with Na(+), K(+)-ATPase (NKA), the FXYD domain-containing ion
      transport regulator (FXYD) is involved in teleost osmoregulation, but knowledge
      of FXYD in marine fish is limited. In the present study, fxyd11 and fxyd12 were
      identified from the spotted scat (Scatophagus argus), and the two members of the
      FXYD protein family were expressed in a tissue-specific manner. Fxyd11 mRNA was
      predominantly expressed in gills, whereas fxyd12 mRNA was mainly distributed in
      kidneys and intestines. Acute hyposaline stress altered the activity of NKA and
      the expression of fxyd11 and fxyd12 in gills, kidneys, and intestines. Branchial
      fxyd11 mRNA expression remained at a low level during freshwater acclimation,
      whereas NKA activity increased, showing a negative correlation that differed from
      previous reports. Similarly, renal expression of fxyd11 and fxyd12 mRNA was
      negatively correlated with NKA activity. Unlike in gills and kidneys, intestinal
      NKA activity and mRNA expression of fxyd11 and fxyd12 were comparably suppressed.
      Taken together, the salinity-dependent expression of fxyd11 and fxyd12, and
      correlation with NKA activity suggested that both fxyd11 and fxyd12 were involved
      in the response to acute hyposaline challenge in the spotted scat. 

PMID- 24878496
TI  - Noise in the operating room.

PMID- 24878495
TI  - General anesthetic isoflurane modulates inositol 1,4,5-trisphosphate receptor
      calcium channel opening.
AB  - BACKGROUND: Pharmacological evidence suggests that inhalational general
      anesthetics induce neurodegeneration in vitro and in vivo through overactivation
      of inositol trisphosphate receptor (InsP3R) Ca-release channels, but it is not
      clear whether these effects are due to direct modulation of channel activity by
      the anesthetics. METHODS: Using single-channel patch clamp electrophysiology, the
      authors examined the gating of rat recombinant type 3 InsP3R (InsP3R-3) Ca
      release channels in isolated nuclei (N = 3 to 15) from chicken lymphocytes
      modulated by isoflurane at clinically relevant concentrations in the absence and
      presence of physiological levels of the agonist inositol 1,4,5-trisphosphate
      (InsP3). The authors also examined the effects of isoflurane on InsP3R-mediated
      Ca release from the endoplasmic reticulum and changes in intracellular Ca
      concentration ([Ca]i). RESULTS: Clinically relevant concentrations (approximately
      1 minimal alveolar concentration) of the commonly used general anesthetic,
      isoflurane, activated InsP3R-3 channels with open probability similar to channels
      activated by 1 uM InsP3 (Po ~ 0.2). This isoflurane modulation of InsP3R-3 Po
      depended biphasically on [Ca]i. Combination of isoflurane with subsaturating
      levels of InsP3 in patch pipettes resulted in at least two-fold augmentations of
      InsP3R-3 channel Po compared with InsP3 alone. These effects were not noted in
      the presence of saturating [InsP3]. Application of isoflurane to DT40 cells
      resulted in a 30% amplification of InsP3R-mediated [Ca]i oscillations, whereas
      InsP3-induced increase in [Ca]i and cleaved caspase-3 activity were enhanced by
      approximately 2.5-fold. CONCLUSION: These results suggest that the InsP3R may be
      a direct molecular target of isoflurane and plays a role in the mechanisms of
      anesthetic-mediated pharmacological or neurotoxic effects.

PMID- 24878499
TI  - Aortic dissection complicated with haemothorax - an autopsy report.
AB  - In a forensic setting, haemothorax is usually seen in cases of trauma. The main
      non-traumatic cause for haemothorax is an intrathoracic rupture of an acute
      aortic dissection or an aortic aneurysm that is almost always fatal. Here we
      present one such case of sudden natural death caused by rupture of an acute
      aortic dissection. The deceased was a middle-aged, unidentified male who was
      subjected to autopsy at the Department of Forensic Medicine, M.S. Ramaiah Medical
      College, after having been brought in dead to the hospital. It is a type III
      DeBakey dissection as it originates in the descending aorta and it is quite
      unusual that a rare retrograde extension was also observed. 

PMID- 24878497
TI  - Highly precise quantification of protein molecules per cell during stress and
      starvation responses in Bacillus subtilis.
AB  - Systems biology based on high quality absolute quantification data, which are
      mandatory for the simulation of biological processes, successively becomes
      important for life sciences. We provide protein concentrations on the level of
      molecules per cell for more than 700 cytosolic proteins of the Gram-positive
      model bacterium Bacillus subtilis during adaptation to changing growth
      conditions. As glucose starvation and heat stress are typical challenges in B.
      subtilis' natural environment and induce both, specific and general stress and
      starvation proteins, these conditions were selected as models for starvation and
      stress responses. Analyzing samples from numerous time points along the bacterial
      growth curve yielded reliable and physiologically relevant data suitable for
      modeling of cellular regulation under altered growth conditions. The analysis of
      the adaptational processes based on protein molecules per cell revealed stress
      specific modulation of general adaptive responses in terms of protein amount and
      proteome composition. Furthermore, analysis of protein repartition during glucose
      starvation showed that biomass seems to be redistributed from proteins involved
      in amino acid biosynthesis to enzymes of the central carbon metabolism. In
      contrast, during heat stress most resources of the cell, namely those from amino
      acid synthetic pathways, are used to increase the amount of chaperones and
      proteases. Analysis of dynamical aspects of protein synthesis during heat stress
      adaptation revealed, that these proteins make up almost 30% of the protein mass
      accumulated during early phases of this stress. 

PMID- 24878500
TI  - Reply: Infantile Leigh-like syndrome caused by SLC19A3 mutations is a treatable
      disease.

PMID- 24878498
TI  - PepExplorer: a similarity-driven tool for analyzing de novo sequencing results.
AB  - Peptide spectrum matching is the current gold standard for protein identification
      via mass-spectrometry-based proteomics. Peptide spectrum matching compares
      experimental mass spectra against theoretical spectra generated from a protein
      sequence database to perform identification, but protein sequences not present in
      a database cannot be identified unless their sequences are in part conserved. The
      alternative approach, de novo sequencing, can make it possible to infer a peptide
      sequence directly from a mass spectrum, but interpreting long lists of peptide
      sequences resulting from large-scale experiments is not trivial. With this as
      motivation, PepExplorer was developed to use rigorous pattern recognition to
      assemble a list of homologue proteins using de novo sequencing data coupled to
      sequence alignment to allow biological interpretation of the data. PepExplorer
      can read the output of various widely adopted de novo sequencing tools and
      converge to a list of proteins with a global false-discovery rate. To this end,
      it employs a radial basis function neural network that considers precursor charge
      states, de novo sequencing scores, peptide lengths, and alignment scores to
      select similar protein candidates, from a target-decoy database, usually obtained
      from phylogenetically related species. Alignments are performed using a modified
      Smith-Waterman algorithm tailored for the task at hand. We verified the
      effectiveness of our approach using a reference set of identifications generated
      by ProLuCID when searching for Pyrococcus furiosus mass spectra on the
      corresponding NCBI RefSeq database. We then modified the sequence database by
      swapping amino acids until ProLuCID was no longer capable of identifying any
      proteins. By searching the mass spectra using PepExplorer on the modified
      database, we were able to recover most of the identifications at a 1% false
      discovery rate. Finally, we employed PepExplorer to disclose a comprehensive
      proteomic assessment of the Bothrops jararaca plasma, a known biological source
      of natural inhibitors of snake toxins. PepExplorer is integrated into the
      PatternLab for Proteomics environment, which makes available various tools for
      downstream data analysis, including resources for quantitative and differential
      proteomics. 

PMID- 24878501
TI  - Reply: Infantile Leigh-like syndrome caused by SLC19A3 mutations is a treatable
      disease.

PMID- 24878494
TI  - Epigenetic regulation of estrogen-dependent memory.
AB  - Hippocampal memory formation is highly regulated by post-translational histone
      modifications and DNA methylation. Accordingly, these epigenetic processes play a
      major role in the effects of modulatory factors, such as sex steroid hormones, on
      hippocampal memory. Our laboratory recently demonstrated that the ability of the
      potent estrogen 17beta-estradiol (E2) to enhance hippocampal-dependent novel
      object recognition memory in ovariectomized female mice requires ERK-dependent
      histone H3 acetylation and DNA methylation in the dorsal hippocampus. Although
      these data provide valuable insight into the chromatin modifications that mediate
      the memory-enhancing effects of E2, epigenetic regulation of gene expression is
      enormously complex. Therefore, more research is needed to fully understand how E2
      and other hormones employ epigenetic alterations to shape behavior. This review
      discusses the epigenetic alterations shown thus far to regulate hippocampal
      memory, briefly reviews the effects of E2 on hippocampal function, and describes
      in detail our work on epigenetic regulation of estrogenic memory enhancement. 

PMID- 24878502
TI  - Infantile Leigh-like syndrome caused by SLC19A3 mutations is a treatable disease.

PMID- 24878503
TI  - Alona iheringula Sinev & Kotov, 2004 (Crustacea, Anomopoda, Chydoridae,
      Aloninae): life cycle and DNA barcode with implications for the taxonomy of the
      Aloninae subfamily.
AB  - Knowledge of reproductive rates and life cycle of the Cladocera species is
      essential for population dynamic studies, secondary production and food webs, as
      well as the management and preservation of aquatic ecosystems. The present study
      aimed to understand the life cycle and growth of Alona iheringula Kotov & Sinev,
      2004 (Crustacea, Anomopoda, Chydoridae), a Neotropical species, as well as its
      DNA barcoding, providing new information on the Aloninae taxonomy. The specimens
      were collected in the dammed portion of the Cabo Verde River (21 degrees 26'05" S
      and 46 degrees 10'57" W), in the Furnas Reservoir, Minas Gerais State, Brazil.
      Forty neonates were observed individually two or three times a day under
      controlled temperature (25+/-1 degrees C), photoperiod (12 h light/12 h dark) and
      feeding (Pseudokirchneriella subcapitata at a concentration of 105 cells.mL-1 and
      a mixed suspension of yeast and fish feed in equal proportion). Individual body
      growth was measured daily under optical microscope using a micrometric grid and
      40* magnification. The species had a mean size of 413(+/-29) um, a maximum size
      of 510 um and reached maturity at 3.24(+/-0.69) days of age. Mean fecundity was 2
      eggs per female per brood and the mean number of eggs produced per female during
      the entire life cycle was 47.6(+/-6.3) eggs per female. The embryonic development
      time was 1.79(+/-0.23) days and the maximum longevity was 54 days. The species
      had eight instars throughout its life cycle and four instars between neonate and
      primipara stage. The present study using molecular data (a 461 bp smaller COI
      fragment) demonstrated a deep divergence in the Aloninae subfamily. 

PMID- 24878504
TI  - Individualistic population responses of five frog species in two changing
      tropical environments over time.
AB  - Roughly 40% of amphibian species are in decline with habitat loss, disease, and
      climate change being the most cited threats. Heterogeneity of extrinsic (e.g.
      climate) and intrinsic (e.g. local adaptations) factors across a species' range
      should influence population response to climate change and other threats. Here we
      examine relative detectability changes for five direct-developing leaf litter
      frogs between 42-year sampling periods at one Lowland Tropical Forest site (51
      m.a.s.l.) and one Premontane Wet Forest site (1100 m.a.s.l.) in southwest Costa
      Rica. We identify individualistic changes in relative detectability among
      populations between sampling periods at different elevations. Both common and
      rare species showed site-specific declines, and no species exhibited significant
      declines at both sites. Detection changes are correlated with changes in
      temperature, dry season rainfall, and leaf litter depth since 1969. Our study
      species share Least Concern conservation status, life history traits, and close
      phylogenetic relationship, yet their populations changed individualistically both
      within and among species. These results counter current views of the uniformity
      or predictability of amphibian decline response and suggest additional complexity
      for conservation decisions.

PMID- 24878505
TI  - Pancreatic cancer cell glycosylation regulates cell adhesion and invasion through
      the modulation of alpha2beta1 integrin and E-cadherin function.
AB  - In our previous studies we have described that ST3Gal III transfected pancreatic
      adenocarcinoma Capan-1 and MDAPanc-28 cells show increased membrane expression
      levels of sialyl-Lewis x (SLe(x)) along with a concomitant decrease in alpha2,6
      sialic acid compared to control cells. Here we have addressed the role of this
      glycosylation pattern in the functional properties of two glycoproteins involved
      in the processes of cancer cell invasion and migration, alpha2beta1 integrin, the
      main receptor for type 1 collagen, and E-cadherin, responsible for cell-cell
      contacts and whose deregulation determines cell invasive capabilities. Our
      results demonstrate that ST3Gal III transfectants showed reduced cell-cell
      aggregation and increased invasive capacities. ST3Gal III transfected Capan-1
      cells exhibited higher SLe(x) and lower alpha2,6-sialic acid content on the
      glycans of their alpha2beta1 integrin molecules. As a consequence, higher
      phosphorylation of focal adhesion kinase tyrosine 397, which is recognized as one
      of the first steps of integrin-derived signaling pathways, was observed in these
      cells upon adhesion to type 1 collagen. This molecular mechanism underlies the
      increased migration through collagen of these cells. In addition, the pancreatic
      adenocarcinoma cell lines as well as human pancreatic tumor tissues showed
      colocalization of SLe(x) and E-cadherin, which was higher in the ST3Gal III
      transfectants. In conclusion, changes in the sialylation pattern of alpha2beta1
      integrin and E-cadherin appear to influence the functional role of these two
      glycoproteins supporting the role of these glycans as an underlying mechanism
      regulating pancreatic cancer cell adhesion and invasion.

PMID- 24878507
TI  - Bioluminescence imaging of stroke-induced endogenous neural stem cell response.
AB  - Brain injury following stroke affects neurogenesis in the adult mammalian brain.
      However, a complete understanding of the origin and fate of the endogenous neural
      stem cells (eNSCs) in vivo is missing. Tools and technology that allow non
      invasive imaging and tracking of eNSCs in living animals will help to overcome
      this hurdle. In this study, we aimed to monitor eNSCs in a photothrombotic (PT)
      stroke model using in vivo bioluminescence imaging (BLI). In a first strategy,
      inducible transgenic mice expressing firefly luciferase (Fluc) in the eNSCs were
      generated. In animals that received stroke, an increased BLI signal originating
      from the infarct region was observed. However, due to histological limitations,
      the identity and exact origin of cells contributing to the increased BLI signal
      could not be revealed. To overcome this limitation, we developed an alternative
      strategy employing stereotactic injection of conditional lentiviral vectors (Cre
      Flex LVs) encoding Fluc and eGFP in the subventricular zone (SVZ) of Nestin-Cre
      transgenic mice, thereby specifically labeling the eNSCs. Upon induction of
      stroke, increased eNSC proliferation resulted in a significant increase in BLI
      signal between 2days and 2weeks after stroke, decreasing after 3months.
      Additionally, the BLI signal relocalized from the SVZ towards the infarct region
      during the 2weeks following stroke. Histological analysis at 90days post stroke
      showed that in the peri-infarct area, 36% of labeled eNSC progeny differentiated
      into astrocytes, while 21% differentiated into mature neurons. In conclusion, we
      developed and validated a novel imaging technique that unequivocally demonstrates
      that nestin(+) eNSCs originating from the SVZ respond to stroke injury by
      increased proliferation, migration towards the infarct region and differentiation
      into both astrocytes and neurons. In addition, this new approach allows non
      invasive and specific monitoring of eNSCs over time, opening perspectives for
      preclinical evaluation of candidate stroke therapeutics. 

PMID- 24878506
TI  - Factors and models associated with the amount of hospital care services as
      demanded by hospitalized patients: a systematic review.
AB  - BACKGROUND: Hospitals are constantly being challenged to provide high-quality
      care despite ageing populations, diminishing resources, and budgetary restraints.
      While the costs of care depend on the patients' needs, it is not clear which
      patient characteristics are associated with the demand for care and inherent
      costs. The aim of this study was to ascertain which patient-related
      characteristics or models can predict the need for medical and nursing care in
      general hospital settings. METHODS: We systematically searched MEDLINE, Embase,
      Business Source Premier and CINAHL. Pre-defined eligibility criteria were used to
      detect studies that explored patient characteristics and health status parameters
      associated to the use of hospital care services for hospitalized patients. Two
      reviewers independently assessed study relevance, quality with the STROBE
      instrument, and performed data analysis. RESULTS: From 2,168 potentially relevant
      articles, 17 met our eligibility criteria. These showed a large variety of
      factors associated with the use of hospital care services; models were found in
      only three studies. Age, gender, medical and nursing diagnoses, severity of
      illness, patient acuity, comorbidity, and complications were the characteristics
      found the most. Patient acuity and medical and nursing diagnoses were the most
      influencing characteristics. Models including medical or nursing diagnoses and
      patient acuity explain the variance in the use of hospital care services for at
      least 56.2%, and up to 78.7% when organizational factors were added. CONCLUSIONS:
      A larger variety of factors were found to be associated with the use of hospital
      care services. Models that explain the extent to which hospital care services are
      used should contain patient characteristics, including patient acuity, medical or
      nursing diagnoses, and organizational and staffing characteristics, e.g.,
      hospital size, organization of care, and the size and skill mix of staff. This
      would enable healthcare managers at different levels to evaluate hospital care
      services and organize or reorganize patient care.

PMID- 24878508
TI  - Intracellular processing of disease-associated alpha-synuclein in the human brain
      suggests prion-like cell-to-cell spread.
AB  - Dementia with Lewy bodies (DLB), Parkinson's disease (PD) and multiple system
      atrophy are characterized by the deposition of disease-associated alpha
      synuclein. In the present study we 1) examined the molecular specificity of the
      novel anti-alpha-synuclein 5G4 antibody; 2) evaluated immunoreactivity patterns
      and their correlation in human brain tissue with micro- and astrogliosis in 57
      cases with PD or DLB; and 3) performed a systematic immunoelectron microscopical
      mapping of subcellular localizations. 5G4 strongly binds to the high molecular
      weight fraction of beta-sheet rich oligomers, while no binding to primarily
      disordered oligomers or monomers was observed. We show novel localizations of
      disease-associated alpha-synuclein including perivascular macrophages, ependyma
      and cranial nerves. alpha-Synuclein immunoreactive neuropil dots and thin threads
      associate more with glial reaction than Lewy bodies alone. Astrocytic alpha
      synuclein is an important component of the pathology. Furthermore, we document
      ultrastructurally the pathway of processing of disease-associated alpha-synuclein
      within neurons and astroglial cells. Interaction of mitochondria and disease
      associated alpha-synuclein plays a key role in the molecular-structural
      cytopathogenesis of disorders with Lewy bodies. We conclude that 1) the 5G4
      antibody has strong selectivity for beta-sheet rich alpha-synuclein oligomers; 2)
      Lewy bodies themselves are not the most relevant morphological substrate that
      evokes tissue lesioning; 3) both neurons and astrocytes internalize disease
      associated alpha-synuclein in the human brain, suggesting prion-like cell-to-cell
      spread of alpha-synuclein by uptake from surrounding structures, as shown
      previously in experimental observations. 

PMID- 24878509
TI  - LDB3 splicing abnormalities are specific to skeletal muscles of patients with
      myotonic dystrophy type 1 and alter its PKC binding affinity.
AB  - Myotonic dystrophy type 1 (DM1) is caused by transcription of CUG repeat RNA,
      which causes sequestration of muscleblind-like 1 (MBNL1) and upregulation of CUG
      triplet repeat RNA-binding protein (CUG-BP1). In DM1, dysregulation of these
      proteins contributes to many aberrant splicing events, causing various symptoms
      of the disorder. Here, we demonstrate the occurrence of aberrant splicing of LIM
      domain binding 3 (LDB3) exon 11 in DM1 skeletal muscle. Exon array surveys, RT
      PCR, and western blotting studies demonstrated that exon 11 inclusion was DM1
      specific and could be reproduced by transfection of a minigene containing the CTG
      repeat expansion. Moreover, we found that the LDB3 exon 11-positive isoform had
      reduced affinity for PKC compared to the exon 11-negative isoform. Since PKC
      exhibits hyperactivation in DM1 and stabilizes CUG-BP1 by phosphorylation,
      aberrant splicing of LDB3 may contribute to CUG-BP1 upregulation through changes
      in its affinity for PKC. 

PMID- 24878511
TI  - Activation of Akt/FKHR in the medulla oblongata contributes to spontaneous
      respiratory recovery after incomplete spinal cord injury in adult rats.
AB  - After incomplete spinal cord injury (SCI), patients and animals may exhibit some
      spontaneous functional recovery which can be partly attributed to remodeling of
      injured neural circuitry. This post-lesion plasticity implies spinal remodeling
      but increasing evidences suggest that supraspinal structures contribute also to
      the functional recovery. Here we tested the hypothesis that partial SCI may
      activate cell-signaling pathway(s) at the supraspinal level and that this
      molecular response may contribute to spontaneous recovery. With this aim, we used
      a rat model of partial cervical hemisection which injures the bulbospinal
      respiratory tract originating from the medulla oblongata of the brainstem but
      leads to a time-dependent spontaneous functional recovery of the paralyzed
      hemidiaphragm. We first demonstrate that after SCI the PI3K/Akt signaling pathway
      is activated in the medulla oblongata of the brainstem, resulting in an
      inactivation of its pro-apoptotic downstream target, forkhead transcription
      factor (FKHR/FOXO1A). Retrograde labeling of medullary premotoneurons including
      respiratory ones which project to phrenic motoneurons reveals an increased FKHR
      phosphorylation in their cell bodies together with an unchanged cell number.
      Medulla infusion of the PI3K inhibitor, LY294002, prevents the SCI-induced Akt
      and FKHR phosphorylations and activates one of its death-promoting downstream
      targets, Fas ligand. Quantitative EMG analyses of diaphragmatic contractility
      demonstrate that the inhibition of medulla PI3K/Akt signaling prevents
      spontaneous respiratory recovery normally observed after partial cervical SCI.
      Such inhibition does not however affect either baseline contractile frequency or
      the ventilatory reactivity under acute respiratory challenge. Together, these
      findings provide novel evidence of supraspinal cellular contribution to the
      spontaneous respiratory recovery after partial SCI. 

PMID- 24878515
TI  - The physician quality officer model: 5-year follow-up.
AB  - Physician engagement is a key element of health care quality improvement.
      Challenges include competing demands, inconsistent compensation, knowledge
      deficits, and lack of mentorship and role modeling. To help address these
      obstacles, UMass Memorial Medical Center developed a physician quality officer
      (PQO) program in 2007. Since its inception, several elements of the program have
      changed, including PQO roles in projects, approaches to training, logistics of
      group communication, the role of PQOs in medical staff education, and the PQO
      compensation model. 

PMID- 24878512
TI  - Phylogeny and ultrastructure of Oxymonas jouteli, a Rostellum-free species, and
      Opisthomitus longiflagellatus sp. nov., Oxymonadid flagellates from the gut of
      Neotermes jouteli.
AB  - The biodiversity of oxymonadid flagellates in termite hindguts is not fully
      explored. Many species have been differentiated only by morphological features,
      and small-celled species have been overlooked or ignored. Our analysis of the dry
      wood termite Neotermes jouteli by light and electron microscopy revealed the
      presence of two distinct morphotypes of oxymonads. The larger one matched the
      morphology of Oxymonas jouteli, the only oxymonad species described from this
      termite. Although it generally lacks the typical anterior rostellum of the genus
      Oxymonas, its SSU rRNA gene sequence clusters among other members of this genus,
      including novel phylotypes that we obtained from Incisitermes tabogae. The second
      morphotype was a tiny oxymonad that showed the typical traits of the genus
      Opisthomitus, including a pointed anterior prolongation (lappet). However, the
      four equal flagella were much longer than those of Opisthomitus avicularis from
      Kalotermes flavicollis, the only species of the genus and so far described only
      by light microscopy. We provide a detailed description of Opisthomitus
      longiflagellatus sp. nov. and demonstrate that despite ultrastructural
      similarities to members of the Polymastigidae, its SSU rRNA gene sequences form a
      separate family-level lineage with a slight affinity to the Pyrsonymphidae.

PMID- 24878510
TI  - DLK-dependent signaling is important for somal but not axonal degeneration of
      retinal ganglion cells following axonal injury.
AB  - Injury to retinal ganglion cell (RGC) axons triggers rapid activation of Jun N
      terminal kinase (JNK) signaling, a major prodeath pathway in injured RGCs. Of the
      multiple kinases that can activate JNK, dual leucine kinase (Dlk) is known to
      regulate both apoptosis and Wallerian degeneration triggered by axonal insult.
      Here we tested the importance of Dlk in regulating somal and axonal degeneration
      of RGCs following axonal injury. Removal of DLK from the developing optic cup did
      not grossly affect developmental RGC death or inner plexiform layer organization.
      In the adult, Dlk deficiency significantly delayed axonal-injury induced RGC
      death. The activation of JUN was also attenuated in Dlk deficient retinas. Dlk
      deficiency attenuated the activation of the somal pool of JNK but did not prevent
      activation of the axonal pool of JNK after axonal injury, indicating that JNK
      activation in different cellular compartments of an RGC following axonal injury
      is regulated by distinct upstream kinases. In contrast to its robust influence on
      somal degeneration, Dlk deficiency did not alter RGC axonal degeneration after
      axonal injury as assessed using physiological readouts of optic nerve function. 

PMID- 24878514
TI  - Feedback to achieve improved sign-out technique.
AB  - To maximize the quality of sign-out documents within the internal medicine
      residency, a quality improvement intervention was developed and implemented.
      Written sign-outs were collected from general medicine ward teams and graded
      using an 11-point checklist; in-person feedback was then given directly to the
      ward teams. Documentation of many of the 11 elements improved: mental status (22%
      to 66%, P < .0001), decisionality (40% to 66%, P < .0001), lab/test results (63%
      to 69%, P < .0001), level of acuity (34% to 50%, P < .0001), anticipatory
      guidance (69% to 82%, P < .0001), and future plans (35% to 38%, P < .0005). The
      use of vague language declined (41% to 26%, P < .0001). The mean total scores
      improved from 7.0 to 8.2 out of a possible 11 (P < .0001). As new house staff
      rotated onto the services, improvement over time was sustained with 1 feedback
      session per team, per month. Similar interventions could be made in other
      programs and other institutions. 

PMID- 24878517
TI  - Violated expectancies: Cause and function of exploration, fear, and aggression.
AB  - To be able to reproduce, animals need to survive and interact with an ever
      changing environment. Therefore, they create a cognitive representation of that
      environment, from which they derive expectancies regarding current and future
      events. These expected events are compared continuously with information gathered
      through exploration, to guide behaviour and update the existing representation.
      When a moderate discrepancy between perceived and expected events is detected,
      exploration is employed to update the internal representation so as to alter the
      expectancy and make it match the perceived event. When the discrepancy is
      relatively large, exploration is inhibited, and animals will try to alter the
      perceived event utilizing aggression or fear. The largest discrepancies are
      associated with a tendency to flee. When an exploratory, fear, or aggressive
      behaviour pattern proofs to be the optimal solution for a particular discrepancy,
      the response will become conditioned to events that previously preceded the
      occurrence of that discrepancy. When primary needs are relatively low, animals
      will actively look for or create moderately violated expectancies in order to
      learn about objects, behaviour patterns, and the environment. In those
      situations, exploratory tendencies will summate with ongoing behaviour and, when
      all primary needs are satiated, may even be performed exclusively. This results
      in behavioural variability, play, and active information-seeking. This article is
      part of a Special Issue entitled: In Honor of Jerry Hogan.

PMID- 24878516
TI  - Technology integration performance assessment using lean principles in health
      care.
AB  - This study assesses the impact of an automated infusion system (AIS) integration
      at a positron emission tomography (PET) center based on "lean thinking"
      principles. The authors propose a systematic measurement system that evaluates
      improvement in terms of the "8 wastes." This adaptation to the health care
      context consisted of performance measurement before and after integration of AIS
      in terms of time, utilization of resources, amount of materials wasted/saved,
      system variability, distances traveled, and worker strain. The authors'
      observations indicate that AIS stands to be very effective in a busy PET
      department, such as the one in Moffitt Cancer Center, owing to its accuracy,
      pace, and reliability, especially after the necessary adjustments are made to
      reduce or eliminate the source of errors. This integration must be accompanied by
      a process reengineering exercise to realize the full potential of AIS in reducing
      waste and improving patient care and worker satisfaction. 

PMID- 24878518
TI  - Social discrimination of cage-mates and non-cage-mates by rats.
AB  - The ability to discriminate between group-mates and non-group-mates likely
      underpins the occurrence of affiliative and aggressive behaviour towards 'in
      group' and 'out-group' individuals. Here we present two experiments aimed at
      testing the ability of rats (Rattus norvegicus) to discriminate between cage-mate
      (CM: animals residing in the subject's home cage) and non-cage-mate (NCM)
      conspecifics. In experiment 1, rats were trained to discriminate between
      different exemplars of CM and NCM using a lever pressing task employing
      symmetrical reinforcement. Subjects did not reach performance criterion, but they
      did show some evidence of discrimination between the two types of stimuli. In
      experiment 2, we employed a digging task to determine if rats can discriminate
      between odour cues from CM and NCM presented simultaneously on two sand-filled
      bowls. Subjects reached performance criterion on the first pair of odours, and on
      three more different pairs of CM and NCM odours. The results of a reversal task,
      using a fifth pair of odours, indicate that the rats were using a common factor
      to discriminate between social cues from CM and NCM conspecifics, rather than
      learning each pair independently. Possible candidates include a group-specific
      odour cue, or the development of a CM/NCM category concept. 

PMID- 24878519
TI  - Development of a templated approach to fabricate diamond patterns on various
      substrates.
AB  - We demonstrate a robust templated approach to pattern thin films of chemical
      vapor deposited nanocrystalline diamond grown from monodispersed nanodiamond
      (mdND) seeds. The method works on a range of substrates, and we herein
      demonstrate the method using silicon, aluminum nitride (AlN), and sapphire
      substrates. Patterns are defined using photo- and e-beam lithography, which are
      seeded with mdND colloids and subsequently introduced into microwave assisted
      chemical vapor deposition reactor to grow patterned nanocrystalline diamond
      films. In this study, we investigate various factors that affect the selective
      seeding of different substrates to create high quality diamond thin films,
      including mdND surface termination, zeta potential, surface treatment, and plasma
      cleaning. Although the electrostatic interaction between mdND colloids and
      substrates is the main process driving adherence, we found that chemical reaction
      (esterification) or hydrogen bonding can potentially dominate the seeding
      process. Leveraging the knowledge on these different interactions, we optimize
      fabrication protocols to eliminate unwanted diamond nucleation outside the
      patterned areas. Furthermore, we have achieved the deposition of patterned
      diamond films and arrays over a range of feature sizes. This study contributes to
      a comprehensive understanding of the mdND-substrate interaction that will enable
      the fabrication of integrated nanocrystalline diamond thin films for
      microelectronics, sensors, and tissue culturing applications. 

PMID- 24878520
TI  - Synthesis of morphology controllable porous Co3O4 nanostructures with tunable
      textural properties and their catalytic application.
AB  - Porous cobalt oxide (Co3O4) nanorod (50-100 nm) and nanosheet-like (70-100 nm)
      particles were synthesized by a facile hydrothermal method at 150  degrees C for
      2-5 h and 12-24 h, respectively, using aqueous-based precursors like cobalt
      nitrate, urea and water in the absence of any templating agents followed by their
      calcination at 300  degrees C. Morphology and textural properties were tuned by
      changing the synthesis time at 150  degrees C. A 3D architecture of Co3O4 was
      formed by the self-assembly of nanostructured (nanorod and nanosheet) particles.
      The BET surface area, pore volume and pore diameter of the sample prepared at 150
      degrees C for 5 h were 112 m(2) g(-1), 0.5 cm(3) g(-1) and 7.4 nm, respectively,
      and it exhibited the highest catalytic performance with a rate constant of 56.8 *
      10(-3) min(-1) for the degradation of Chicago Sky Blue 6B, a carcinogenic azo dye
      used in the textile, paper and food industries. Rod-like particles with a
      mesoporous structure rendered a better catalytic efficiency than sheet-like
      particles having both microporous and mesoporous structures. An interrelationship
      amongst the morphology, textural properties and the catalytic efficiency of Co3O4
      was established. 

PMID- 24878521
TI  - Effectiveness of a Web-based tailored intervention (E-health4Uth) and
      consultation to promote adolescents' health: randomized controlled trial.
AB  - BACKGROUND: To promote well-being and health behaviors among adolescents, 2
      interventions were implemented at 12 secondary schools. Adolescents in the E
      health4Uth group received Web-based tailored messages focused on their health
      behaviors and well-being. Adolescents in the E-health4Uth and consultation group
      received the same tailored messages, but were subsequently referred to a school
      nurse for a consultation if they were at risk of mental health problems.
      OBJECTIVE: This study evaluated the effect of E-health4Uth and E-health4Uth and
      consultation on well-being (ie, mental health status and health-related quality
      of life) and health behaviors (ie, alcohol and drug use, smoking, safe sex).
      METHODS: A cluster randomized controlled trial was conducted among third- and
      fourth-year secondary school students (mean age 15.9, SD 0.69). School classes
      (clusters) were randomly assigned to (1) E-health4Uth group, (2) E-health4Uth and
      consultation group, or (3) control group (ie, care as usual). Adolescents
      completed a questionnaire at baseline and at 4-month follow-up assessing alcohol
      consumption, smoking, drug use, condom use, mental health via the Strengths and
      Difficulties Questionnaire (SDQ) and the Youth Self Report (YSR; only measured at
      follow-up), and health-related quality of life. Multilevel logistic, ordinal, and
      linear regression analyses were used to reveal differences in health behavior and
      well-being between the intervention groups and the control group at follow-up.
      Subsequently, it was explored whether demographics moderated the effects.
      RESULTS: Data from 1256 adolescents were analyzed. Compared to the control
      intervention, the E-health4Uth intervention, as a standalone intervention, showed
      minor positive results in health-related quality of life (B=2.79, 95% CI 0.72
      4.87) and condom use during intercourse among adolescents of Dutch ethnicity (OR
      3.59, 95% CI 1.71-7.55) not replicated in the E-health4Uth and consultation
      group. The E-health4Uth and consultation intervention showed minor positive
      results in the mental health status of adolescents (SDQ: B=-0.60, 95% CI -1.17 to
      -0.04), but a negative effect on drug use among boys (OR 0.36, 95% CI 0.13-0.96).
      In the subgroup of adolescents who were at risk of mental health problems at
      baseline (and referred for a consultation with the nurse), the E-health4Uth and
      consultation group showed minor to moderate positive results in mental health
      status (SDQ: B=-1.79, 95% CI -3.35 to -0.22; YSR: B=-9.11, 95% CI -17.52 to 
      0.71) and health-related quality of life (B=7.81, 95% CI 2.41-13.21) at follow-up
      compared to adolescents in the control group who were at risk of mental health
      problems at baseline. CONCLUSIONS: Findings from this study support the use of
      the E-health4Uth and consultation intervention in promoting the well-being of
      adolescents at risk of mental health problems. Future research is needed to
      further evaluate the effects of the consultation as a standalone intervention,
      and the dual approach of further tailored eHealth messages and a consultation.
      TRIAL REGISTRATION: Nederlands Trial Register: NTR 3596;
      http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=3596 (Archived by
      WebCite at http://www.webcitation.org/6PmgrPOuv).

PMID- 24878523
TI  - Fatty alcohols can complement functions of heterocyst specific glycolipids in
      Anabaena sp. PCC 7120.
AB  - Heterocyst glycolipid synthase (HglT) catalyzes the final step of heterocyst
      glycolipid (Hgl) biosynthesis, in which a glucose is transferred to the aglycone
      (fatty alcohol). Here we describe the isolation of hglT null mutants. These
      mutants lacked Hgls under nitrogen-starved conditions and instead accumulated
      fatty alcohols. Differentiated heterocyst cells in the mutants were
      morphologically indistinguishable from those of the wild-type cells.
      Interestingly, the mutants grew under nitrogen starvation but fixed nitrogen with
      lower nitrogenase activity than did the wild-type. The mutants had a pale green
      phenotype with a decreased chlorophyll content, especially under nitrogen-starved
      conditions. These results suggest that the glucose moiety of the Hgls may be
      necessary for optimal protection against oxygen influx but is not essential and
      that aglycones can function as barriers against oxygen influx in the heterocyst
      cells. 

PMID- 24878522
TI  - Snail interacts with hPLSCR1 promoter and down regulates its expression in IMR
      32.
AB  - Human phospholipid scramblase 1 (hPLSCR1) is a proapoptotic protein whose
      expression is deregulated in a variety of cancers cells. However till date the
      transcription regulation of hPLSCR1 is unknown. Transcriptional regulation of
      hPLSCR1 was studied by cloning the 5'-flanking region of hPLSCR1. Luciferase
      assays revealed that -1525 to -1244 region of hPLSCR1 was found to regulate its
      promoter activity. A putative Snail transcription factor (TF) binding site was
      found within the regulatory region of the promoter. Snail binding was found to
      down regulate the expression of hPLSCR1 both at the transcriptional and
      translational levels. Snail knock down using Snail-shRNA confirmed that down
      regulation of hPLSCR1 by Snail was specific. Point mutation studies confirm that
      the predicted Snail TF binds to -1123 to -1117 site. ChIP assay further confirms
      the physical interaction of Snail with hPLSCR1 promoter. This is the first report
      showing the transcriptional regulation of hPLSCR1 expression by Snail TF and its
      possible implications in cancer progression. 

PMID- 24878524
TI  - Self/non-self recognition mechanisms in sexual reproduction: new insight into the
      self-incompatibility system shared by flowering plants and hermaphroditic
      animals.
AB  - Sexual reproduction is an essential process for generating a genetic variety in
      the next generation. However, most flowering plants and hermaphroditic animals
      potentially allow self-fertilization. Approximately 60% of angiosperms possess a
      self-incompatibility (SI) system to avoid inbreeding. The SI system functions at
      a process of interaction between pollen (or pollen tube) and the pistil. These SI
      responsible factors (S-determinants) in pollen and the pistil are encoded by
      highly polymorphic multiallelic genes in the S-locus, which are tightly linked
      making a single haplotype. Different taxonomic families utilize different types
      of S-determinant proteins. In contrast to the plant system, the mechanisms of SI
      in simultaneously hermaphroditic animals are largely unknown. Among them,
      promising candidates for SI in ascidians (primitive chordates) were recently
      identified. The SI system in the ascidian Cionaintestinalis was found to be very
      similar to those in flowering plants: The products of sperm- and egg-side
      multiallelic SI genes, which are tight linked and highly polymorphic, appear to
      be responsible for the SI system as revealed by genetic analysis. These findings
      led us to speculate that the SI systems in plants and animals evolved in a manner
      of convergent evolution. Here, we review the current understanding of the
      molecular mechanisms of the SI system in flowering plants, particularly
      Brassicacea, and in ascidians from the viewpoint of common mechanisms shared by
      plants and animals. 

PMID- 24878526
TI  - Conservation of sequence and function in fertilization of the cortical granule
      serine protease in echinoderms.
AB  - Conservation of the cortical granule serine protease during fertilization in
      echinoderms was tested both functionally in sea stars, and computationally
      throughout the echinoderm phylum. We find that the inhibitor of serine protease
      (soybean trypsin inhibitor) effectively blocks proper transition of the sea star
      fertilization envelope into a protective sperm repellent, whereas inhibitors of
      the other main types of proteases had no effect. Scanning the transcriptomes of
      15 different echinoderm ovaries revealed sequences of high conservation to the
      originally identified sea urchin cortical serine protease, CGSP1. These conserved
      sequences contained the catalytic triad necessary for enzymatic activity, and the
      tandemly repeated LDLr-like repeats. We conclude that the protease involved in
      the slow block to polyspermy is an essential and conserved element of
      fertilization in echinoderms, and may provide an important reagent for
      identification and testing of the cell surface proteins in eggs necessary for
      sperm binding. 

PMID- 24878527
TI  - Oxaliplatin antagonizes HIV-1 latency by activating NF-kappaB without causing
      global T cell activation.
AB  - Reactivation of latent HIV-1 is a promising strategy for the clearance of the
      viral reservoirs. Because of the limitations of current agents, identification of
      new latency activators is urgently required. Using an established model of HIV-1
      latency, we examined the effect of Oxaliplatin on latent HIV-1 reactivation. We
      showed that Oxaliplatin, alone or in combination with valproic acid (VPA), was
      able to reactivate HIV-1 without inducing global T cell activation. We also
      provided evidence that Oxaliplatin reactivated HIV-1 expression by inducing
      nuclear factor kappa B (NF-kappaB) nuclear translocation. Our results indicated
      that Oxaliplatin could be a potential drug candidate for anti-latency therapies. 

PMID- 24878525
TI  - Influenza entry pathways in polarized MDCK cells.
AB  - In non-polarized cell culture models, influenza virus has been shown to enter
      host cells via multiple endocytic pathways, including classical clathrin-mediated
      endocytic routes (CME), clathrin- and caveolae-independent routes and
      macropinocytosis. However, little is known about the entry route of influenza
      virus in differentiated epithelia, in vivo site of infection for influenza virus.
      Here, we show that in polarized Madin-Darby canine kidney type II (MDCK II)
      cells, influenza virus has a specific utilization of the clathrin-mediated
      endocytic pathway and requires Eps15 for host cell entry. 

PMID- 24878528
TI  - High concentrations of glucose suppress etoposide-induced cell death of B-cell
      lymphoma through BCL-6.
AB  - Glucose is potentially a factor in the resistance to chemotherapy of B-cell
      lymphomas. In this study we investigated the expression of the glucose induced
      transcription factor Bcl-6 and the underlying mechanism by which it suppresses B
      cell lymphoma cell death. Glucose was found to prevent etoposide-induced tumor
      cell death. BCL-6 expression was induced by glucose but down-regulated by
      etoposide. BCL-6 expression was regulated by the interaction of VDUP1 and p53.
      The molecular mechanism by which glucose prevented etoposide-induced tumor cell
      death was shown to involve the BCL-6 mediated caspase pathway. Our data suggest
      that glucose-induced BCL-6 overexpression could abrogate the etoposide
      chemotherapy effect on tumor cell death. 

PMID- 24878529
TI  - Matrix metalloproteinase-14 is a mechanically regulated activator of secreted
      MMPs and invasion.
AB  - Matrix metalloproteinases (MMPs) are extracellular matrix (ECM) degrading enzymes
      and have complex and specific regulation networks. This includes activation
      interactions, where one MMP family member activates another. ECM degradation and
      MMP activation can be initiated by several different stimuli including changes in
      ECM mechanical properties or intracellular contractility. These mechanical
      stimuli are known enhancers of metastatic potential. MMP-14 facilitates local ECM
      degradation and is well known as a major mediator of cell migration, angiogenesis
      and invasion. Recently, function blocking antibodies have been developed to
      specifically block MMP-14, providing a useful tool for research as well as
      therapeutic applications. Here we utilize a selective MMP-14 function blocking
      antibody to delineate the role of MMP-14 as an activator of other MMPs in
      response to changes in cellular contractility and ECM stiffness. Inhibition using
      function blocking antibodies reveals that MMP-14 activates soluble MMPs like MMP
      2 and -9 under various mechanical stimuli in the pancreatic cancer cell line,
      Panc-1. In addition, inhibition of MMP-14 abates Panc-1 cell extension into 3D
      gels to levels seen with non-specific pan-MMP inhibitors at higher
      concentrations. This strengthens the case for MMP function blocking antibodies as
      more potent and specific MMP inhibition therapeutics. 

PMID- 24878530
TI  - Molecular phylogeny of C1 inhibitor depicts two immunoglobulin-like domains
      fusion in fishes and ray-finned fishes specific intron insertion after separation
      from zebrafish.
AB  - C1 inhibitor (C1IN) is a multi-facet serine protease inhibitor in the plasma
      cascades, inhibiting several proteases, notably, regulates both complement and
      contact system activation. Despite huge advancements in the understanding of C1IN
      based on biochemical properties and its roles in the plasma cascades, the
      phylogenetic history of C1IN remains uncharacterized. To date, there is no
      comprehensive study illustrating the phylogenetic history of C1IN. Herein, we
      explored phylogenetic history of C1IN gene in vertebrates. Fishes have C1IN with
      two immunoglobulin like domains attached in the N-terminal region. The RCL
      regions of CIIN from fishes and tetrapod genomes have variations at the positions
      P2 and P1'. Gene structures of C1IN gene from selected ray-finned fishes varied
      in the Ig domain region with creation of novel intron splitting exon Im2 into
      Im2a and Im2b. This intron is limited to ray-finned fishes with genome size
      reduced below 1 Gb. Hence, we suggest that genome compaction and associated
      double-strand break repairs are behind this intron gain. This study reveals the
      evolutionary history of C1IN and confirmed that this gene remains the same locus
      for ~450 MY in 52 vertebrates analysed, but it is not found in frogs and
      lampreys.

PMID- 24878531
TI  - Bacterial multidrug efflux pumps: mechanisms, physiology and pharmacological
      exploitations.
AB  - Multidrug resistance (MDR) refers to the capability of bacterial pathogens to
      withstand lethal doses of structurally diverse drugs which are capable of
      eradicating non-resistant strains. MDR has been identified as a major threat to
      the public health of human being by the World Health Organization (WHO). Among
      the four general mechanisms that cause antibiotic resistance including target
      alteration, drug inactivation, decreased permeability and increased efflux, drug
      extrusion by the multidrug efflux pumps serves as an important mechanism of MDR.
      Efflux pumps not only can expel a broad range of antibiotics owing to their poly
      substrate specificity, but also drive the acquisition of additional resistance
      mechanisms by lowering intracellular antibiotic concentration and promoting
      mutation accumulation. Over-expression of multidrug efflux pumps have been
      increasingly found to be associated with clinically relevant drug resistance. On
      the other hand, accumulating evidence has suggested that efflux pumps also have
      physiological functions in bacteria and their expression is subject tight
      regulation in response to various of environmental and physiological signals. A
      comprehensive understanding of the mechanisms of drug extrusion, and regulation
      and physiological functions of efflux pumps is essential for the development of
      anti-resistance interventions. In this review, we summarize the development of
      these research areas in the recent decades and present the pharmacological
      exploitation of efflux pump inhibitors as a promising anti-drug resistance
      intervention. 

PMID- 24878533
TI  - Editing of the heavy chain gene of Bombyx mori using transcription activator like
      effector nucleases.
AB  - The silk gland of Bombyx mori represents an established in vivo system for
      producing recombinant proteins. However, low yields of recombinant proteins have
      limited the system's further development because endogenous silk proteins were
      present. Transcription activator-like effector nucleases (TALENs) tool which work
      in pairs to bind and cleave DNA at specific sites, have recently been shown to be
      effective for genome editing in various organisms, including silkworms. To
      improve the yield of recombinant proteins synthesized in the silkworm by
      eliminated competition with endogenous fibroin synthesis, the heavy chain (H
      chain) gene was knocked out using transcription activator-like effector nucleases
      (TALENs). A pair of TALENs that targets the 1st exon in the H-chain gene was
      synthesized and microinjected into silkworm embryos; the injected silkworms were
      screened for H-chain gene knock out (H-KO) based on their sericin cocoon-making
      characteristics. Sequence analysis revealed that the H-chain of the mutation was
      successfully edited. The TALENs was very efficient in editing the genome DNA of
      silkworm. By being eliminated competition with the H-chain, the production of
      recombinant proteins would be expected to increase markedly if this H-KO system
      is used. 

PMID- 24878532
TI  - Slow and sustained nitric oxide releasing compounds inhibit multipotent vascular
      stem cell proliferation and differentiation without causing cell death.
AB  - Atherosclerosis is the leading cause of cerebral and myocardial infarction. It is
      believed that neointimal growth common in the later stages of atherosclerosis is
      a result of vascular smooth muscle cell (SMC) de-differentiation in response to
      endothelial injury. However, the claims of the SMC de-differentiation theory have
      not been substantiated by monitoring the fate of mature SMCs in response to such
      injuries. A recent study suggests that atherosclerosis is a consequence of
      multipotent vascular stem cell (MVSC) differentiation. Nitric oxide (NO) is a
      well-known mediator against atherosclerosis, in part because of its inhibitory
      effect on SMC proliferation. Using three different NO-donors, we have
      investigated the effects of NO on MVSC proliferation. Results indicate that NO
      inhibits MVSC proliferation in a concentration dependent manner. A slow and
      sustained delivery of NO proved to inhibit proliferation without causing cell
      death. On the other hand, larger, single-burst NO concentrations, inhibits
      proliferation, with concurrent significant cell death. Furthermore, our results
      indicate that endogenously produced NO inhibits MVSC differentiation to
      mesenchymal-like stem cells (MSCs) and subsequently to SMC as well. 

PMID- 24878535
TI  - Identification of lysosomotropic compounds based on the distribution and size of
      lysosomes.
AB  - Lysosomal accumulation of drugs with their specific physicochemical properties is
      of key importance to drug distribution in the body. Several attempts have been
      made to treat various human diseases by employing the accumulation of lysosomal
      drugs, and many methods to identify lysosomal accumulation of drugs have been
      proposed. Among those, the use of high-content screening has increased
      tremendously because of improved efficiency and accuracy as well as the
      development of automatic image acquisition and analytical techniques.
      Conventional methods to identify lysosomal accumulation of drugs by evaluating
      changes in the lysosomal area are unable to maximize the advantages of phenotypic
      high-content screening. Lysosomal distribution and the size of lysosomes are
      affected by lysosomal accumulating drugs. Therefore, we present image acquisition
      conditions and analytical methods to utilize lysosomal distribution and size as
      parameters for identifying lysosomal accumulating drugs. These two parameters
      will help to improve the reliability of the screening methods for identifying
      lysosomal accumulation of drugs by maximizing usage of information from image
      based screening. 

PMID- 24878534
TI  - Apamin inhibits hepatic fibrosis through suppression of transforming growth
      factor beta1-induced hepatocyte epithelial-mesenchymal transition.
AB  - Apamin is an integral part of bee venom, as a peptide component. It has long been
      known as a highly selective block Ca(2+)-activated K(+) (SK) channels. However,
      the cellular mechanism and anti-fibrotic effect of apamin in TGF-beta1-induced
      hepatocytes have not been explored. In the present study, we investigated the
      anti-fibrosis or anti-EMT mechanism by examining the effect of apamin on TGF
      beta1-induced hepatocytes. AML12 cells were seeded at ~60% confluence in complete
      growth medium. Twenty-four hours later, the cells were changed to serum free
      medium containing the indicated concentrations of apamin. After 30 min, the cells
      were treated with 2 ng/ml of TGF-beta1 and co-cultured for 48 h. Also, we
      investigated the effects of apamin on the CCl4-induced liver fibrosis animal
      model. Treatment of AML12 cells with 2 ng/ml of TGF-beta1 resulted in loss of E
      cadherin protein at the cell-cell junctions and concomitant increased expression
      of vimentin. In addition, phosphorylation levels of ERK1/2, Akt, Smad2/3 and
      Smad4 were increased by TGF-beta1 stimulation. However, cells treated
      concurrently with TGF-beta1 and apamin retained high levels of localized
      expression of E-cadherin and showed no increase in vimentin. Specifically,
      treatment with 2 MUg/ml of apamin almost completely blocked the phosphorylation
      of ERK1/2, Akt, Smad2/3 and Smad4 in AML12 cells. In addition, apamin exhibited
      prevention of pathological changes in the CCl4-injected animal models. These
      results demonstrate the potential of apamin for the prevention of EMT progression
      induced by TGF-beta1 in vitro and CCl4-injected in vivo.

PMID- 24878536
TI  - Understanding the rise in cardiovascular diseases in Africa: harmonising H3Africa
      genomic epidemiological teams and tools.
AB  - Cardiovascular diseases, principally ischaemic heart disease and stroke, are the
      leading causes of global mortality and morbidity. Together with other non
      communicable diseases, they account for more than 60% of global deaths and pose
      major social, economic and developmental challenges worldwide. In Africa, there
      is now compelling evidence that the major cardiovascular disease (CVD) risk
      factors are on the rise, and so are the related fatal and non-fatal sequelae,
      which occur at significantly younger ages than seen in high-income countries. In
      order to tackle this rising burden of CVD, the H3Africa Cardiovascular Working
      Group will hold an inaugural workshop on 30 May 2014 in Cape Town, South Africa.
      The primary workshop objectives are to enhance our understanding of the genetic
      underpinnings of the common major CVDs in Africa and strengthen collaborations
      among the H3Africa teams and other researchers using novel genomic and
      epidemiological tools to contribute to reducing the burden of CVD on the
      continent. 

PMID- 24878537
TI  - Part Two: Evaluation of N-methylbupropion as a Potential Bupropion Prodrug.
AB  - N-methylbupropion was selected as a potential prodrug from our in vitro screening
      of analogues of bupropion described in the preceding paper. This study describes
      in vivo pharmacokinetics of N-methylbupropion in the guinea-pig animal model,
      which is reported to best predict human metabolism of bupropion. The suitability
      of the guinea pig was established by studying N-demethylation of N
      methylbupropion using S9 liver fractions. An LC-MS method was developed and
      validated to measure N-methylbupropion, bupropion and their metabolites in plasma
      and brain tissue. In separate studies, the prodrug was delivered by
      intraperitoneal injection (IP) to assess hepatic metabolism and then by oral
      gavage (PO) to assess the contribution from intestinal enzymes. Bupropion was
      administered in parallel. The pharmacokinetic profile of bupropion and N
      methylbupropion were not comparable when dosed by intraperitoneal injection but
      when dosed orally, N-methylbupropion showed a comparable bupropion and metabolite
      PK plasma profile to bupropion. Plasma and brain levels of N-methylbupropion show
      that it is extensively metabolized to bupropion and its metabolites, and N-methyl
      threo-hydrobupropion. This data coupled to the reduced DAT and NET system in
      vitro activity described in paper 1 would suggest that the N-methyl derivative of
      bupropion may have potential as an oral prodrug of bupropion in humans. 

PMID- 24878538
TI  - The smart 2-(2-fluorobenzoyl)-N-(2-methoxyphenyl)hydrazinecarbothioamide
      functionalized as Ni(II) sensor in micromolar concentration level and its
      application in live cell imaging.
AB  - In recent years, fluorescent probes for the detection of environmentally and
      biologically important metal cations have received extensive attention for
      designing and development of fluorescent chemosensors. Herein, we report the
      photophysical results of 2-(2-fluorobenzoyl)-N-(2-methoxyphenyl)
      hydrazinecarbothioamide (4) functionalized as Ni (II) sensor in micromolar
      concentration level. Through fluorescence titration at 488 nm, we were confirmed
      that ligand 4 showed the remarkable emission by complexation between 4 and Ni
      (II) while it appeared no emission in case of the competitive ions (Cr(3+),
      Fe(2+), Co(2+), Ba(2+), Cu(2+), Ca(2+), Na(+), K(+), Cu(+), Cs(+)). Furthermore,
      ligand 4 exhibited no toxicity with precise cell permeability toward normal
      living cells using L929 cell lines in bio imaging experiment investigated through
      confocal fluorescence microscope. The non-toxic behavior of ligand 4 (assessed by
      MTT assay) and its ability to track the Ni(2+) in living cells suggest its
      possibility to use in biological system as nickel sensor.

PMID- 24878539
TI  - Expression and functional analysis of Toll-like receptor 4 in human cervical
      carcinoma.
AB  - Toll-like receptors are expressed in human immune cells and many tumors, but the
      role of toll-like receptor 4 (TLR4) in the development of tumors is
      controversial. We demonstrated the expression, distribution, and functional
      activity of TLR4 in tissues of normal cervix, cervical intraepithelial neoplasia
      (CIN), invasion cervical cancers (ICC), and different human papillomavirus (HPV)
      infected cervical cancer cells. The results showed that TLR4 expression was in
      accordance with the histopathological grade: higher in ICC than in CIN, and low
      in normal cervical tissues and malignant cervical stroma. Expression was higher
      in SiHa (HPV16+) than in HeLa (HPV18+) cells, but was not observed in C33A (HPV-)
      cells. After treatment with its agonist, lipopolysaccharide (LPS), the expression
      levels of TLR4 was increased and apoptosis resistance was induced in SiHa cells,
      but not in HeLa or C33A cells. Meanwhile, LPS treatment did not alter the cell
      cycle distribution in SiHa cells. The mechanism of apoptosis resistance may be
      related to HPV16 infection and not correlated with the cell cycle distribution.
      Targeting TLR4 in combination with traditional drug treatment may serve as a
      novel strategy for more effectively killing cancer cells. 

PMID- 24878540
TI  - COUP-TFs and eye development.
AB  - Recent studies reveal that COUP-TF genes are essential for neural development,
      cardiovascular development, energy metabolism and adipogenesis, as well as for
      organogenesis of multiple systems. In this review, we mainly describe the COUP-TF
      genes, molecular mechanisms of COUP-TF action, and their crucial functions in the
      morphogenesis of the murine eye. Mutations of COUP-TF genes lead to the
      congenital coloboma and/or optic atrophy in both mouse and human, indicating that
      the study on COUP-TFs and the eye will benefit our understanding of the etiology
      of human ocular diseases. This article is part of a Special Issue entitled:
      Nuclear receptors in animal development. 

PMID- 24878541
TI  - Bile acid signaling and liver regeneration.
AB  - The liver is able to regenerate itself in response to partial hepatectomy or
      liver injury. This is accomplished by a complex network of different cell types
      and signals both inside and outside the liver. Bile acids (BAs) are recently
      identified as liver-specific metabolic signals and promote liver regeneration by
      activating their receptors: Farnesoid X Receptor (FXR) and G-protein-coupled BA
      receptor 1 (GPBAR1, or TGR5). FXR is a member of the nuclear hormone receptor
      superfamily of ligand-activated transcription factors. FXR promotes liver
      regeneration after 70% partial hepatectomy (PHx) or liver injury. Moreover,
      activation of FXR is able to alleviate age-related liver regeneration defects.
      Both liver- and intestine-FXR are activated by BAs after liver resection or
      injury and promote liver regeneration through distinct mechanism. TGR5 is a
      membrane-bound BA receptor and it is also activated during liver regeneration.
      TGR5 regulates BA hydrophobicity and stimulates BA excretion in urine during
      liver regeneration. BA signaling thus represents a novel metabolic pathway during
      liver regeneration. This article is part of a Special Issue entitled: Nuclear
      receptors in animal development. 

PMID- 24878542
TI  - GATA4 represses an ileal program of gene expression in the proximal small
      intestine by inhibiting the acetylation of histone H3, lysine 27.
AB  - GATA4 is expressed in the proximal 85% of small intestine where it promotes a
      proximal intestinal ('jejunal') identity while repressing a distal intestinal
      ('ileal') identity, but its molecular mechanisms are unclear. Here, we tested the
      hypothesis that GATA4 promotes a jejunal versus ileal identity in mouse intestine
      by directly activating and repressing specific subsets of absorptive enterocyte
      genes by modulating the acetylation of histone H3, lysine 27 (H3K27), a mark of
      active chromatin, at sites of GATA4 occupancy. Global analysis of mouse jejunal
      epithelium showed a statistically significant association of GATA4 occupancy with
      GATA4-regulated genes. Occupancy was equally distributed between down- and up
      regulated targets, and occupancy sites showed a dichotomy of unique motif over
      representation at down- versus up-regulated genes. H3K27ac enrichment at GATA4
      binding loci that mapped to down-regulated genes (activation targets) was
      elevated, changed little upon conditional Gata4 deletion, and was similar to
      control ileum, whereas H3K27ac enrichment at GATA4-binding loci that mapped to up
      regulated genes (repression targets) was depleted, increased upon conditional
      Gata4 deletion, and approached H3K27ac enrichment in wild-type control ileum.
      These data support the hypothesis that GATA4 both activates and represses
      intestinal genes, and show that GATA4 represses an ileal program of gene
      expression in the proximal small intestine by inhibiting the acetylation of
      H3K27. 

PMID- 24878544
TI  - Characterizing the Late Pleistocene MSA Lithic Technology of Sibudu, KwaZulu
      Natal, South Africa.
AB  - Studies of the African Middle Stone Age (MSA) have become central for defining
      the cultural adaptations that accompanied the evolution of modern humans. While
      much of recent research in South Africa has focused on the Still Bay and
      Howiesons Poort (HP), periods following these technocomplexes were often
      neglected. Here we examine lithic assemblages from Sibudu that post-date the HP
      to further the understanding of MSA cultural variability during the Late
      Pleistocene. Sibudu preserves an exceptionally thick, rich, and high-resolution
      archaeological sequence that dates to ~ 58 ka, which has recently been proposed
      as type assemblage for the "Sibudan". This study presents a detailed analysis of
      the six uppermost lithic assemblages from these deposits (BM-BSP) that we
      excavated from 2011-2013. We define the key elements of the lithic technology and
      compare our findings to other assemblages post-dating the HP. The six lithic
      assemblages provide a distinct and robust cultural signal, closely resembling
      each other in various technological, techno-functional, techno-economic, and
      typological characteristics. These results refute assertions that modern humans
      living after the HP possessed an unstructured and unsophisticated MSA lithic
      technology. While we observed several parallels with other contemporaneous MSA
      sites, particularly in the eastern part of southern Africa, the lithic
      assemblages at Sibudu demonstrate a distinct and so far unique combination of
      techno-typological traits. Our findings support the use of the Sibudan to help
      structuring this part of the southern African MSA and emphasize the need for
      further research to identify the spatial and temporal extent of this proposed
      cultural unit.

PMID- 24878543
TI  - Risk of pneumonia with inhaled corticosteroid versus long-acting bronchodilator
      regimens in chronic obstructive pulmonary disease: a new-user cohort study.
AB  - INTRODUCTION: Observational studies using case-control designs have showed an
      increased risk of pneumonia associated with inhaled corticosteroid (ICS)
      containing medications in patients with chronic obstructive pulmonary disease
      (COPD). New-user observational cohort designs may minimize biases associated with
      previous case-control designs. OBJECTIVE: To estimate the association between ICS
      and pneumonia among new users of ICS relative to inhaled long-acting
      bronchodilator (LABD) monotherapy. METHODS: Pneumonia events in COPD patients
      >=45 years old were compared among new users of ICS medications (n = 11,555; ICS,
      ICS/long-acting beta2-agonist [LABA] combination) and inhaled LABD monotherapies
      (n = 6,492; LABA, long-acting muscarinic antagonists) using Cox proportional
      hazards models, with propensity scores to adjust for confounding. SETTING: United
      Kingdom electronic medical records with linked hospitalization and mortality data
      (2002-2010). New users were censored at earliest of: pneumonia event, death,
      changing/discontinuing treatment, or end of follow-up. OUTCOMES: severe pneumonia
      (primary) and any pneumonia (secondary). RESULTS: Following adjustment, new use
      of ICS-containing medications was associated with an increased risk of pneumonia
      hospitalization (n = 322 events; HR = 1.55, 95% CI: 1.14, 2.10) and any pneumonia
      (n = 702 events; HR = 1.49, 95% CI: 1.22, 1.83). Crude incidence rates of any
      pneumonia were 48.7 and 30.9 per 1000 person years among the ICS-containing and
      LABD cohorts, respectively. Excess risk of pneumonia with ICS was reduced when
      requiring >=1 month or >= 6 months of new use. There was an apparent dose-related
      effect, with greater risk at higher daily doses of ICS. There was evidence of
      channeling bias, with more severe patients prescribed ICS, for which the analysis
      may not have completely adjusted. CONCLUSIONS: The results of this new-user
      cohort study are consistent with published findings; ICS were associated with a
      20-50% increased risk of pneumonia in COPD, which reduced with exposure time.
      This risk must be weighed against the benefits when prescribing ICS to patients
      with COPD.

PMID- 24878545
TI  - Population genetic structure of a sandstone specialist and a generalist heath
      species at two levels of sandstone patchiness across the Strait of Gibraltar.
AB  - Many habitat specialist species are originally composed of small, discontinuous
      populations because their habitats are naturally fragmented or patchy. They may
      have suffered the long-term effects of natural patchiness. Mediterranean
      heathlands, a representative habitat in the Strait of Gibraltar region, are
      associated with nutrient-poor, acidic sandstone soils. Sandstone soil patches in
      the African side of the Strait (Tangier) are, in general, smaller and more
      scattered than in the European side (Algeciras). In this study, we analyze the
      effect of this sandstone patchiness on the population genetic diversity and
      structure of two Erica species from these Mediterranean heathlands that differ in
      their edaphic specificity, E. australis, sandstone specialist, and E. arborea,
      generalist. Average levels of within-population genetic diversity and gene flow
      between populations were significantly lower in Tangier (high sandstone
      patchiness) than in Algeciras (low patchiness) for the sandstone specialist,
      whereas no differences between both sides of the Strait were detected in the
      edaphic generalist. Since most endemic species in Mediterranean heathlands of the
      Strait of Gibraltar are sandstone specialists, these results highlight an
      increased vulnerability to loss of genetic diversity and local extinction of the
      heathland endemic flora in the Tangier side of the Strait of Gibraltar. 

PMID- 24878546
TI  - Diapause induction and termination in Hyphantria cunea (Drury) (Lepidoptera:
      Arctiinae).
AB  - The fall webworm, Hyphantria cunea (Drury), enters facultative diapause as a pupa
      in response to short-day conditions during autumn. Photoperiodic response curves
      showed that the critical day length for diapause induction was 14 h 30 min, 14 h
      25 min and 13 h 30 min at 22, 25 and 28 degrees C, respectively. The
      photoperiodic responses under non-24 h light-dark cycles demonstrated that night
      length played an essential role in the determination of diapause. Experiments
      using a short day length interrupted by a 1-h light pulse exhibited two troughs
      of diapause inhibition and the effect of diapause inhibition was greater in the
      early scotophase than in the late scotophase. The diapause-inducing short day
      lengths of 8, 10 and 12 h evoked greater intensities of diapause than did 13 and
      14 h. Diapause can be terminated without exposure to chilling, but chilling at 5
      degrees C for 90 and 120 d significantly accelerated diapause development,
      reduced mortality, and synchronized adult emergence. Additionally, the potential
      for H. cunea from the temperate region (Qingdao) to emerge and overwinter under
      field conditions in subtropical regions (Nanchang) of China was evaluated. Pupae
      that were transferred to Nanchang in early July showed a 60% survival rate and
      extremely dispersed pupal period (from 12 to 82 days), suggesting that some pupae
      may undergo summer diapause. Diapausing temperate region pupae that were moved
      out-of-doors in Nanchang during October showed approximately 20% overwintering
      survival; moreover, those pupae that overwintered successfully emerged the next
      spring during a period when their host plants would be available. The results
      indicate that this moth has the potential to expand its range into subtropical
      regions of China. 

PMID- 24878548
TI  - Voxel model of individual cells and its implementation in microdosimetric
      calculations using GEANT4.
AB  - Accurate dosimetric calculations at cellular and sub-cellular levels are crucial
      to obtain an increased understanding of the interactions of ionizing radiation
      with a cell and its nucleus and cytoplasm. Ion microbeams provide a superior
      opportunity to irradiate small biological samples, e.g., DNA, cells, and to
      compare their response to computer simulations. However, the phantoms used to
      simulate small biological samples at cellular levels are often simplified as
      simple volumes filled with water. As a first step to improve the situation in
      comparing measurements of cell response to ionizing radiation with model
      calculations, a realistic voxel model of a KB cell was constructed and used
      together with an already constructed geometry and tracking 4 (GEANT4) model of
      the horizontal microbeam line of the Centre d'Etudes Nucleaires de Bordeaux
      Gradignan (CENBG) 3.5 MV Van de Graaf accelerator at the CENBG, France. The
      microbeam model was then implemented into GEANT4 for simulations of the average
      number of particles hitting an irradiated cell when a specified number of
      particles are produced in the beam line. The result shows that when irradiating
      the developed voxel model of a KB cell with 200 alpha particles, with a nominal
      energy of 3 MeV in the beam line and 2.34 MeV at the cell entrance, 100 particles
      hit the cell on average. The mean specific energy is 0.209 +/- 0.019 Gy in the
      nucleus and 0.044 +/- 0.001 Gy in the cytoplasm. These results are in agreement
      with previously published data, which indicates that this model could act as a
      reference model for dosimetric calculations of radiobiological experiments, and
      that the proposed method could be applied to build a cell model database. 

PMID- 24878549
TI  - Monoparesis of upper extremity due to ipsilateral upper cervical cord
      compression: report of two cases.

PMID- 24878550
TI  - Atypical ulnar fracture associated with long-term bisphosphonate use.

PMID- 24878551
TI  - Characterizing and locating air pollution sources in a complex industrial
      district using optical remote sensing technology and multivariate statistical
      modeling.
AB  - Emissions of volatile organic compounds (VOCs) are most frequent environmental
      nuisance complaints in urban areas, especially where industrial districts are
      nearby. Unfortunately, identifying the responsible emission sources of VOCs is
      essentially a difficult task. In this study, we proposed a dynamic approach to
      gradually confine the location of potential VOC emission sources in an industrial
      complex, by combining multi-path open-path Fourier transform infrared
      spectrometry (OP-FTIR) measurement and the statistical method of principal
      component analysis (PCA). Close-cell FTIR was further used to verify the VOC
      emission source by measuring emitted VOCs from selected exhaust stacks at
      factories in the confined areas. Multiple open-path monitoring lines were
      deployed during a 3-month monitoring campaign in a complex industrial district.
      The emission patterns were identified and locations of emissions were confined by
      the wind data collected simultaneously. N,N-Dimethyl formamide (DMF), 2-butanone,
      toluene, and ethyl acetate with mean concentrations of 80.0 +/- 1.8, 34.5 +/-
      0.8, 103.7 +/- 2.8, and 26.6 +/- 0.7 ppbv, respectively, were identified as the
      major VOC mixture at all times of the day around the receptor site. As the toxic
      air pollutant, the concentrations of DMF in air samples were found exceeding the
      ambient standard despite the path-average effect of OP-FTIR upon concentration
      levels. The PCA data identified three major emission sources, including PU
      coating, chemical packaging, and lithographic printing industries. Applying
      instrumental measurement and statistical modeling, this study has established a
      systematic approach for locating emission sources. Statistical modeling (PCA)
      plays an important role in reducing dimensionality of a large measured dataset
      and identifying underlying emission sources. Instrumental measurement, however,
      helps verify the outcomes of the statistical modeling. The field study has
      demonstrated the feasibility of using multi-path OP-FTIR measurement. The wind
      data incorporating with the statistical modeling (PCA) may successfully identify
      the major emission source in a complex industrial district.

PMID- 24878552
TI  - Removal and mechanism of Cu (II) and Cd (II) from aqueous single-metal solutions
      by a novel biosorbent from waste-activated sludge.
AB  - The removal and mechanism of Cu(2+) and Cd(2+) from aqueous single-metal
      solutions were investigated by using a novel biosorbent from waste-activated
      sludge. A series of adsorption experiments was designed to disclose the effects
      of the key factors on the adsorption capacity of the biosorbent for the metal
      ions. The mass ratio of the biosorbent to metal ion was optimized as 2 to balance
      the adsorption capacity and the removal efficiency. A right shaking speed (150
      r/min) not only ensured enough contact frequency between the sorbent and the
      adsorbate but also reduced the mass transfer resistance. The natural pH value
      (about 5.5) of the metal solutions benefited a high adsorption capacity of the
      biosorbent and avoided the consumption of acid or base for pH adjustment. The
      adsorption reactions belonged to the endothermic process between 15 and 45 
      degrees C. As the scanning electron microscopy (SEM) images showed, the meshy
      structure with long chains and many branches was ideal for the biosorbent to
      quickly capture the metal ions. The energy-dispersive X-ray (EDX) spectra
      confirmed that the adsorbed metal ions lay in the precipitates of the adsorption
      reactions. According to the FTIR analyses, the functional groups responsible for
      Cu(2+) adsorption majorly consisted of O-H, N-H, COOH, CONH2, and the groups
      containing sulfur and phosphorus, while those for Cd(2+) adsorption contained O
      H, N-H, COOH, and CONH2. The differences in the responsible functional groups
      explained the phenomenon that the adsorption capacity of the biosorbent for
      Cu(2+) was higher than that for Cd(2+).

PMID- 24878553
TI  - Anatomical and physiological responses of Colorado blue spruce to vehicle
      exhausts.
AB  - In order to examine whether the leaves of the Colorado blue spruce (Picea
      pungens) are damaged or not by traffic pollution, the traits of the anatomy and
      physiology of its leaves are investigated by exposure to vehicle exhausts in a
      laboratory experiment lasting 30 days. The results show that both the anatomical
      structures and physiological traits of the leaves are significantly affected by
      vehicle exhausts. The anatomical structures, including epidermis, cuticle,
      palisade, and spongy parenchyma are modified when exposed to the high
      concentrations (>= 0.4 mg/m(3)) of vehicle exhausts. However, physiological
      traits such as total chlorophyll content are not changed when exposed to
      different concentrations of vehicle exhaust. Unlike the total chlorophyll
      content, the electrical conductivities increased, whereas the POD activities
      decreased when presented in vehicle exhausts. The present study indicates that
      the Colorado blue spruce changes its anatomical structures and physiological
      traits to avoid possible damage by vehicle exhausts.

PMID- 24878554
TI  - Degradation of PAHs in soil by Lasiodiplodia theobromae and enhanced
      benzo[a]pyrene degradation by the addition of Tween-80.
AB  - Benzo[a]pyrene (BaP), a five-ring polycyclic aromatic hydrocarbon (PAH), which
      has carcinogenic potency, is highly recalcitrant and resistant to microbial
      degradation. A novel fungus, Lasiodiplodia theobromae (L. theobromae), which can
      degrade BaP as a sole carbon source in liquid, was isolated in our laboratory. To
      prompt the further application of L. theobromae in remediation of sites polluted
      by BaP and other PAHs, the present study was targeted toward the removal of BaP
      and PAHs from soil by L. theobromae. The degradation of BaP by L. theobromae was
      studied using a soil spiked with 50 mg/kg BaP. L. theobromae could remove 32.1 %
      of the BaP after 35 days of cultivation. Phenanthrene (PHE) inhibited BaP
      degradation as a competitive substrate. The tested surfactants enhanced BaP
      degradation in soil by different extents, and a removal rate of 92.1 % was
      achieved at a Tween-80 (TW-80) concentration of 5 g/kg. It was revealed that TW
      80 could not only enhance BaP bioavailability by increasing its aqueous
      solubility and decreasing the size of its colloid particles but also increase
      enzyme secretion from L. theobromae and the population of L. theobromae.
      Moreover, ergosterol content together with the biomass C indicated the increase
      in L. theobromae biomass during the BaP biodegradation process in soils. Finally,
      a soil from a historically PAH-contaminated field at Beijing Coking Plant in
      China was tested to assess the feasibility of applying L. theobromae in the
      remediation of polluted sites. The total removal rate of PAHs by L. theobromae
      was 53.3 %, which is 13.1 % higher than that by Phanerochaete chrysosporium (P.
      chrysosporium), an effective PAH degrader. The addition of TW-80 to the field
      soil further enhanced PAH degradation to 73.2 %. Hence, L. theobromae is a
      promising novel strain to be implemented in the remediation of soil polluted by
      PAHs.

PMID- 24878555
TI  - Distribution of feminizing compounds in the aquatic environment and
      bioaccumulation in wild tilapia tissues.
AB  - This study sampled six times of river water, sediment, and tilapia (Oreochromis
      niloticus) in the Dan-Shui River, Taipei, Taiwan; 10 feminizing compounds were
      analyzed using ultra-performance liquid chromatography-tandem mass spectrometry.
      Bisphenol A (508 +/- 634 ng/L, geometric mean (GM) 303 ng/L) and nonylphenol (491
      +/- 570 ng/L, GM 328 ng/L) were the most abundant among analytes in the river
      water. Nonylphenol (770 +/- 602 ng/g wet weight, GM 617 ng/g wet weight) was also
      the highest in sediment. Fish may uptake nonylphenol and nonylphenol ethoxylates
      from river water and sediment because there were significant correlations between
      the concentrations in these matrixes and those in fish tissues (r s ranged from
      0.21 to 0.49, p < 0.05). The bioaccumulation of nonylphenol, nonylphenol
      ethoxylates and bisphenol A in gonad, eggs, and liver was much higher than that
      in muscle (e.g. mean bioaccumulation factors of nonylphenol were 27,287, 20,971,
      9,576 and 967, respectively) and might result in low liver fractions in fish body
      weights (0.66 % +/- 0.39 %, GM 0.55 %) and the skewed sex ratio of fish (male to
      female = 0.52). This innovative study linked the environmental and internal doses
      statistically in the globally distributed wild fish by analyzing feminizing
      compounds in water, sediment, and four fish tissues including gonad and eggs.

PMID- 24878556
TI  - Occurrence of 1,1'-dimethyl-4,4'-bipyridinium (Paraquat) in irrigated soil of the
      Lake Chad Basin, Niger.
AB  - Increased use of agrochemical products to improve yields for irrigated crops in
      sub-Saharan Africa has been accompanied by a significant increase in the risk of
      environmental contamination. Detailed examples of the fate of pesticides after
      initial spreading on crop fields are scarce in tropical regions, where safe
      practices and related health risks are poorly understood by smallholder farmers.
      In the semi-arid environment of the Lake Chad Basin, SE Niger, both intrinsic
      properties of pesticides and extrinsic factors such as soil and climate helped to
      characterize processes leading to an accumulation of pesticides in soils.
      Analysis by HPLC-UV of a 6 m deep soil profile showed the presence of Paraquat at
      concentrations from 953 +/- 102 MUg kg(-1) to 3083 +/- 175 MUg kg(-1) at depths
      between 0.80 and 2.75 m below the land surface. Soil analysis revealed that up to
      approximately 15 % of the total soil matrix consists of smectites, a clay mineral
      capable of retaining cationic pesticides such as Paraquat, and a very low content
      of organic matter (<0.15 wt.% TOC). Paraquat could be stored and not bioavailable
      in a clayey barrier at approximately 2-m depth and therefore does not represent
      an immediate risk for populations or environment in this form. However, if the
      Paraquat application rate remains constant, the clayey barrier could reach a
      saturation limit within 150-200 years and 180-220 years if we consider a DT50 in
      soil of ~1,000 days (FAO). Consequently, it could lead to a deeper infiltration
      and so a pollution of groundwater. Such a scenario can represent a health risk
      for drinking water and for the Lake Chad, which is a major resource for this
      densely populated region of semi-arid Africa. Further analyses should focus on
      deeper layers and groundwater Paraquat contents to validate or invalidate the
      hypothesis of storage in this clay-rich layer.

PMID- 24878557
TI  - Assessment of imposex and butyltin concentrations in Gemophos viverratus (Kiener,
      1834), from Sao Vicente, Republic of Cabo Verde (Africa).
AB  - This work constitutes the first assessment of tributyltin (TBT) pollution levels
      in the Republic of Cabo Verde (Africa) and proposes the marine gastropod Gemophos
      viverratus (Kiener, 1834) as a new bioindicator of TBT pollution in the
      Macaronesia and west coast of Africa. Specimens were collected between August and
      October 2012 along a gradient of naval traffic in Sao Vicente Island. The results
      clearly indicate an increase of imposex levels (percentage of females affected
      with imposex, 0-100 %; vas deferens sequence index, 0-4.1; relative penis length
      index, 0-54.6 %) and female TBT contamination (from 5 to 37 ngSn g(-1) dry weight
      (dw)) from outside to inside the harbour of Porto Grande Bay and identify this
      area as the focus of TBT pollution in the island. The butyltin degradation index
      for G. viverratus tissues ranged between 1.3 and 2.2, which being above 1
      suggests that a considerable part of TBT inputs to the bay may not be very
      recent. Sterile females were found inside the harbour with an incidence up to
      21.4 %. Considering the existence of a planktonic veliger stage in the life cycle
      of G. viverratus, it is expected that recruitment of newborn individuals can be
      supplied from unaffected breeding females inside and outside the Porto Grande
      Bay, resulting in a reduced impact of TBT pollution on population abundance. G.
      viverratus is very promising to be used as a simple, inexpensive and efficient
      novel tool for TBT pollution biomonitoring in the Macaronesia and west coast of
      Africa, a region for which there is an astonishing lack of information concerning
      levels and ecological impacts of TBT pollution.

PMID- 24878558
TI  - Cytotoxic effect of linear alkylbenzene sulfonate on human intestinal Caco-2
      cells: associated biomarkers for risk assessment.
AB  - Linear alkylbenzene sulfonate (LAS) is a synthetic anionic surfactant widely
      present in the environment due to its intensive production and use in the
      detergency field. Admitting that current procedure of risk assessment has limits
      in providing realistic risk assessment data and predicting the cumulative effect
      of the toxicant mixtures, the incorporation of information regarding the mode of
      action and cell response mechanism seems to be a potential solution to overcome
      these limits. In this regard, we investigated in this study the LAS cytotoxicity
      on human intestinal Caco-2 cells, trying to unveil the protein actors implicated
      in the cell response using proteomics approach in order to give a better
      understanding of the toxicological effect and allow the identification of
      appropriate biomarkers reflecting the mode of action associated with LAS. As
      results, we demonstrated that LAS induces a time- and dose-dependent cytotoxicity
      in Caco-2 cells accompanied by an induction of oxidative stress followed by an
      excessive increase of intracellular calcium level. Proteomics approach helped in
      discovering three informative biomarkers of effect associated with LAS cytotoxic
      effect, reported for the first time: calreticulin, thioredoxin, and heat shock
      cognate 71 (HSP7C), confirmed by real-time PCR and western blot analysis. These
      biomarkers could serve for more reliable future risk assessment studies that
      consider the toxicants mode of action in order to help in the prediction of
      potential cumulative effects of environmentally coexisting contaminants.

PMID- 24878559
TI  - Potential toxicity of amphenicol antibiotic: binding of chloramphenicol to human
      serum albumin.
AB  - Antibiotics are widely used in daily life but their abuse has posed a potential
      threat to human health. To evaluate the toxicity of chloramphenicol (CAP) at the
      protein level, the interaction between CAP and human serum albumin (HSA) was
      investigated by fluorescence, Ultraviolet-visible (UV-Vis) absorption, Fourier
      transform infrared (FT-IR) spectroscopy and molecular docking methods.
      Fluorescence data revealed that the fluorescence quenching of HSA by CAP was the
      result of the formation of CAP-HSA complex, and the binding constant was
      determined to be 3.196 * 10(4) L mol(-1) at 310 K. The thermodynamic
      determination indicated that the interaction was driven by enthalpy change and
      entropy change together, where the multiple hydrogen bonds (CAP and the residues
      Arg 222 and His 242 of HSA) and van der Waals forces were the dominant binding
      force. The site marker competition revealed that CAP bound into sub-domain IIA of
      HSA. The binding of CAP induced the drastic reduction in alpha-helix conformation
      and the significant enhancement in beta-sheet conformation of HSA. Molecular
      docking study further confirmed the binding mode obtained by experimental study.
      This work provides a new quantitative evaluation method for antibiotics to cause
      the protein damage.

PMID- 24878560
TI  - PCB153 and p,p'-DDE disorder thyroid hormones via thyroglobulin, deiodinase 2,
      transthyretin, hepatic enzymes and receptors.
AB  - Polychlorinated biphenyls (PCBs) and DDT are widespread environmental persistent
      organic pollutants that have various adverse effects on reproduction, development
      and endocrine function. In order to elucidate effects of PCBs and DDT on thyroid
      hormone homeostasis, Sprague-Dawley rats were dosed with PCB153 and p,p'-DDE
      intraperitoneally (ip) for five consecutive days and sacrificed within 24 h after
      the last dose. Results indicated that after combined exposure to PCB153 and p,p'
      DDE, total thyroxine , free thyroxine, total triiodothyronine, and thyroid
      stimulating hormone in serum were decreased, whereas free triiodothyronine and
      thyrotropin-releasing hormone were not affected. Thyroglobulin and transthyretin
      levels in serum were significantly reduced. mRNA expression of deiodinases 2 (D2)
      was also suppressed, while D1 and D3 levels were not significantly influenced
      after combined exposure. PCB153 and p,p'-DDE induced hepatic enzymes, UDPGTs,
      CYP1A1, CYP2B1, and CYP3A1 mRNA expressions being significantly elevated.
      Moreover, TRalpha1, TRbeta1, and TRHr expressions in the hypothalamus displayed
      increasing trends after combined exposure to PCB153 and p,p'-DDE. Taken together,
      observed results indicate that PCB153 and p,p'-DDE could disorder thyroid hormone
      homeostasis via thyroglobulin, deiodinase 2, transthyretin, hepatic enzymes, and
      hormone receptors.

PMID- 24878562
TI  - Vertical gradients and seasonal variation in stem CO2 efflux within a Norway
      spruce stand.
AB  - Stem CO2 efflux is known to vary seasonally and vertically along tree stems.
      However, annual tree- and stand-scale efflux estimates are commonly based on
      measurements made only a few times a year, during daytime and at breast height.
      In this study, the effect of these simplifying assumptions on annual efflux
      estimates and their influence on the estimates of the importance of stems in
      stand-scale carbon cycling are evaluated. In order to assess the strength of
      seasonal, diurnal and along-stem variability in CO2 efflux, half-hourly
      measurements were carried out at three heights on three mature Norway spruce
      (Picea abies (L.) Karst.) trees over a period of 3 years. Making the common
      assumption of breast height efflux rates being representative of the entire stem
      was found to result in underestimations of 10-17% in the annual tree-scale CO2
      efflux. Upscaling using only daytime measurements from breast height increased
      the underestimation to 15-20%. Furthermore, the results show that the strength of
      the vertical gradient varies seasonally, being strongest in the early summer and
      non-existent during the cool months. The observed seasonality in the vertical CO2
      efflux gradient could not be explained by variation in stem temperature,
      temperature response of the CO2 efflux (Q10), outer-bark permeability, CO2
      transport in the xylem or CO2 release from the phloem. However, the estimated CO2
      concentration immediately beneath the bark was considerably higher in the upper
      stem during the main period of diameter growth, coinciding with the strongest
      vertical efflux gradient. These results suggest that higher growth rates in the
      upper stem are the main cause for the observed vertical variation in the stem CO2
      effluxes. Furthermore, the results indicate that accounting for the vertical
      efflux variation is essential for assessments of the importance of stems in stand
      scale carbon cycling. 

PMID- 24878561
TI  - Environmental concentrations of 3,4-methylenedioxymethamphetamine (MDMA)-induced
      cellular stress and modulated antioxidant enzyme activity in the zebra mussel.
AB  - Recent monitoring studies showed measurable levels of the 3,4
      methylenedioxymethamphetamine (MDMA) in aquatic environments. However, no
      information is currently available on its potential hazard to aquatic non-target
      organisms. The aim of this study was to investigate the potential sub-lethal
      effects induced by 14-day exposures to low MDMA concentrations (0.05 and 0.5
      MUg/L) to zebra mussel (Dreissena polymorpha) specimens through the application
      of a biomarker suite. The trypan blue exclusion method and the neutral red
      retention assay (NRRA) were used to assess MDMA cytotoxicity. The activity of
      superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and
      glutathione S-transferase (GST), as well as the lipid peroxidation (LPO) and
      protein carbonyl content (PCC), were measured as oxidative stress indexes. The
      single cell gel electrophoresis (SCGE) assay, the DNA diffusion assay, and the
      micronucleus test (MN test) were applied to investigate DNA damage, while
      filtration rate was measured as physiological parameter. Despite significant
      decrease in lysosome membrane stability, hemocyte viability and imbalances in CAT
      and GST activities pointed out at the end of the exposure to 0.5 MUg/L, no
      significant variations for the other end points were noticed at both the
      treatments, suggesting that environmentally relevant MDMA concentrations did not
      induce deleterious effects to the zebra mussel.

PMID- 24878564
TI  - Anti-neuronal antibodies associated with a first episode of mania.

PMID- 24878563
TI  - Introduction of an electronic physiological early warning system: effects on
      mortality and length of stay.
AB  - BACKGROUND: The Worthing physiological scoring system (PSS) was first validated
      in 2005 as a tool to predict hospital mortality on admission and was subsequently
      introduced into clinical practice at Worthing Hospital, UK. Five years on, this
      study was conducted to determine the effects on mortality and length of stay
      (LOS) after the introduction of electronic alerting software using the PSS. In
      addition, we investigated whether the Worthing PSS predictive ability could be
      improved by addition of further variables. METHODS: Prospective observational
      study conducted in the acute medical unit, Worthing Hospital, UK. Patient
      physiological data on admission and discharge/transfer were collected between
      February and July 2010 from the electronic alerting software VitalPACTM. Patient
      characteristics, co-morbidity, outcomes, and biochemistry data were taken from
      the hospital administration and pathology systems. RESULTS: The observed
      mortality reduction from 8.3% to 5.2% over 5 yr was not statistically significant
      after adjustment for admission Worthing PSS score. Median LOS was reduced from 4
      to 2 days, but this reflected an increase in short stay admissions. Worthing PSS
      was not significantly improved with the addition of biochemical variables or
      patient co-morbidity. A score taken before admission to a medical ward showed an
      improved predictive ability when compared with the initial admission score, but
      further analysis found no additional clinical benefit. CONCLUSIONS: The
      introduction of an electronic alerting PSS did not lead to a reduction in
      mortality when adjusted for severity of illness defined by physiological
      variables. Predictive performance was not enhanced by the addition of biochemical
      variables and co-morbidities.

PMID- 24878566
TI  - Cronobacter spp.--opportunistic food-borne pathogens. A review of their virulence
      and environmental-adaptive traits.
AB  - The genus Cronobacter consists of a diverse group of Gram-negative bacilli and
      comprises seven species: Cronobacter sakazakii, Cronobacter malonaticus,
      Cronobacter muytjensii, Cronobacter turicensis, Cronobacter dublinensis,
      Cronobacter universalis and Cronobacter condimenti. Cronobacter are regarded as
      opportunistic pathogens, and have been implicated in newborn and infant
      infections, causing meningitis, necrotizing enterocolitis and bacteraemia or
      sepsis. Cronobacter virulence is believed to be due to multiple factors. Some
      strains were found to produce diarrhoea or cause significant fluid accumulation
      in suckling mice. Two iron acquisition systems (eitCBAD and iucABCD/iutA),
      Cronobacter plasminogen activator gene (cpa), a 17 kb type VI secretion system
      (T6SS), and a 27 kb filamentous haemagglutinin gene (fhaBC) and associated
      putative adhesins locus are harboured on a family of RepFIB-related plasmids
      (pESA3 and pCTU1), suggesting that these are common virulence plasmids; 98% of
      229 tested Cronobacter strains possessed these plasmids. Even though pESA3 and
      pCTU1 share a common backbone composed of the repA gene and eitCBAD and
      iucABCD/iutA gene clusters, the presence of cpa, T6SS and FHA loci depended on
      species, demonstrating a strong correlation with the presence of virulence
      traits, plasmid type and species. Other factors were observed, in that
      Cronobacter form biofilms, and show unusual resistance to heat, dry and acid
      stress growth conditions. The outer-membrane protein A is probably one of the
      best-characterized virulence markers of Cronobacter. Furthermore, it was reported
      that Cronobacter employ phosphatidylinositide 3-kinase/Akt signalling, which
      activates protein kinase C-alpha and impairs the host cell's mitogen-activated
      protein kinase pathway, in order to invade cells. Cronobacter can also use
      immature dendritic cells and macrophages to escape the immune response. This
      review addresses the various virulence and environmental-adaptive characteristics
      possessed by members of the genus Cronobacter.

PMID- 24878565
TI  - Spatial and temporal characteristics of normal and perturbed vesicle transport.
AB  - Efficient intracellular transport is essential for healthy cellular function and
      structural integrity, and problems in this pathway can lead to neuronal cell
      death and disease. To spatially and temporally evaluate how transport defects are
      initiated, we adapted a primary neuronal culture system from Drosophila larval
      brains to visualize the movement dynamics of several cargos/organelles along a 90
      micron axonal neurite over time. All six vesicles/organelles imaged showed robust
      bi-directional motility at both day 1 and day 2. Reduction of motor proteins
      decreased the movement of vesicles/organelles with increased numbers of neurite
      blocks. Neuronal growth was also perturbed with reduction of motor proteins.
      Strikingly, we found that all blockages were not fixed, permanent blocks that
      impeded transport of vesicles as previously thought, but that some blocks were
      dynamic clusters of vesicles that resolved over time. Taken together, our
      findings suggest that non-resolving blocks may likely initiate deleterious
      pathways leading to death and degeneration, while resolving blocks may be benign.
      Therefore evaluating the spatial and temporal characteristics of vesicle
      transport has important implications for our understanding of how transport
      defects can affect other pathways to initiate death and degeneration. 

PMID- 24878568
TI  - CRISPR/Cas-mediated targeted mutagenesis in Daphnia magna.
AB  - The water flea Daphnia magna has been used as an animal model in ecology,
      evolution, and environmental sciences. Thanks to the recent progress in Daphnia
      genomics, genetic information such as the draft genome sequence and expressed
      sequence tags (ESTs) is now available. To investigate the relationship between
      phenotypes and the available genetic information about Daphnia, some gene
      manipulation methods have been developed. However, a technique to induce targeted
      mutagenesis into Daphnia genome remains elusive. To overcome this problem, we
      focused on an emerging genome editing technique mediated by the clustered
      regularly interspaced short palindromic repeats/CRISPR-associated (CRISPR/Cas)
      system to introduce genomic mutations. In this study, we targeted a functionally
      conserved regulator of eye development, the eyeless gene in D. magna. When we
      injected Cas9 mRNAs and eyeless-targeting guide RNAs into eggs, 18-47% of the
      survived juveniles exhibited abnormal eye morphology. After maturation, up to
      8.2% of the adults produced progenies with deformed eyes, which carried mutations
      in the eyeless loci. These results showed that CRISPR/Cas system could introduce
      heritable mutations into the endogenous eyeless gene in D. magna. This is the
      first report of a targeted gene knockout technique in Daphnia and will be useful
      in uncovering Daphnia gene functions. 

PMID- 24878567
TI  - Zebrafish reporter lines reveal in vivo signaling pathway activities involved in
      pancreatic cancer.
AB  - Pancreatic adenocarcinoma, one of the worst malignancies of the exocrine
      pancreas, is a solid tumor with increasing incidence and mortality in
      industrialized countries. This condition is usually driven by oncogenic KRAS
      point mutations and evolves into a highly aggressive metastatic carcinoma due to
      secondary gene mutations and unbalanced expression of genes involved in the
      specific signaling pathways. To examine in vivo the effects of KRAS(G12D) during
      pancreatic cancer progression and time correlation with cancer signaling pathway
      activities, we have generated a zebrafish model of pancreatic adenocarcinoma in
      which eGFP-KRAS(G12D) expression was specifically driven to the pancreatic tissue
      by using the GAL4/UAS conditional expression system. Outcrossing the inducible
      oncogenic KRAS(G12D) line with transgenic zebrafish reporters, harboring specific
      signaling responsive elements of transcriptional effectors, we were able to
      follow TGFbeta, Notch, Bmp and Shh activities during tumor development. Zebrafish
      transgenic lines expressing eGFP-KRAS(G12D) showed normal exocrine pancreas
      development until 3 weeks post fertilization (wpf). From 4 to 24 wpf we observed
      several degrees of acinar lesions, characterized by an increase in mesenchymal
      cells and mixed acinar/ductal features, followed by progressive bowel and liver
      infiltrations and, finally, highly aggressive carcinoma. Moreover, live imaging
      analysis of the exocrine pancreatic tissue revealed an increasing number of KRAS
      positive cells and progressive activation of TGFbeta and Notch pathways. Increase
      in TGFbeta, following KRAS(G12D) activation, was confirmed in a concomitant model
      of medulloblastoma (MDB). Notch and Shh signaling activities during tumor onset
      were different between MDB and pancreatic adenocarcinoma, indicating a tissue
      specific regulation of cell signaling pathways. Moreover, our results show that a
      living model of pancreatic adenocarcinoma joined with cell signaling reporters is
      a suitable tool for describing in vivo the signaling cascades and molecular
      mechanisms involved in tumor development and a potential platform to screen for
      novel oncostatic drugs. 

PMID- 24878569
TI  - DNA barcodes of Rosy Tetras and allied species (Characiformes: Characidae:
      Hyphessobrycon) from the Brazilian Amazon basin.
AB  - DNA barcoding can be an effective tool for fast and accurate species-level
      identification based on sequencing of the mitochondrial cytochrome c oxidase
      subunit (COI) gene. The diversity of this fragment can be used to estimate the
      richness of the respective species. In this study, we explored the use of DNA
      barcoding in a group of ornamental freshwater fish of the genus Hyphessobrycon.
      We sequenced the COI from 10 species of Hyphessobrycon belonging to the "Rosy
      Tetra Clade" collected from the Amazon and Negro River basins and combined our
      results with published data. The average conspecific and congeneric Kimura 2
      parameter distances were 2.3% and 19.3%, respectively. Six of the 10 species were
      easily distinguishable by DNA barcoding (H. bentosi, H. copelandi, H. eques, H.
      epicharis, H. pulchrippinis, and H. sweglesi), whereas the remaining species (H.
      erythrostigma, H. pyrrhonotus, H. rosaceus and H. socolofi) lacked reciprocal
      monophyly. Although the COI gene was not fully diagnostic, the discovery of
      distinct evolutionary units in certain Hyphessobrycon species under the same
      specific epithet as well as haplotype sharing between different species suggest
      that DNA barcoding is useful for species identification in this speciose genus. 

PMID- 24878572
TI  - Spatial, demographic and clinical patterns of Angiostrongylus vasorum infection
      in the dog population of Southern England.
AB  - A retrospective study was carried out to provide updated knowledge of the spatial
      pattern of Angiostrongylus vasorum infection in Southern England and to
      investigate associations between selected host characteristics (age, breed, sex),
      risk of infection and clinical presentation (cardiorespiratory signs v
      haemorrhagic diathesis). One hundred and forty-one cases diagnosed between April
      1999 and July 2012 were compared with a control population of dogs referred to
      the same hospital. A significant association was found between haemorrhagic
      diathesis and breed but not for other host characteristics and clinical
      presentations. Younger dogs and certain breeds of dog (Jack Russell terriers,
      Cocker Spaniels, Springer Spaniels, Cavalier King Charles spaniels and
      Staffordshire Bull Terriers) had significantly higher odds of angiostrongylosis
      than other breeds in the study. A significant cluster of cases was found in
      Southern England. Animals presenting with cardiorespiratory signs or haemorrhagic
      diathesis in Southern England, especially if they are young or of a breed
      associated with angiostrongylosis, should be given special consideration with
      regards to possible A. vasorum infestation. Our results should be interpreted
      bearing in mind that they are based on the retrospective exploration of dogs seen
      at a referral centre.

PMID- 24878570
TI  - Characterization of Scedosporium apiospermum glucosylceramides and their
      involvement in fungal development and macrophage functions.
AB  - Scedosporium apiospermum is an emerging fungal pathogen that causes both
      localized and disseminated infections in immunocompromised patients.
      Glucosylceramides (CMH, GlcCer) are the main neutral glycosphingolipids expressed
      in fungal cells. In this study, glucosylceramides (GlcCer) were extracted and
      purified in several chromatographic steps. Using high-performance thin layer
      chromatography (HPTLC) and electrospray ionization mass spectrometry (ESI-MS), N
      2'-hydroxyhexadecanoyl-1-beta-D-glucopyranosyl-9-methyl-4,8-sphingadienine was
      identified as the main GlcCer in S. apiospermum. A monoclonal antibody (Mab)
      against this molecule was used for indirect immunofluorescence experiments, which
      revealed that this CMH is present on the surface of the mycelial and conidial
      forms of S. apiospermum. Treatment of S. apiospermum conidia with the Mab
      significantly reduced fungal growth. In addition, the Mab also enhanced the
      phagocytosis and killing of S. apiospermum by murine cells. In vitro assays were
      performed to evaluate the CMHs for their cytotoxic activities against the
      mammalian cell lines L.929 and RAW, and an inhibitory effect on cell
      proliferation was observed. Synergistic in vitro interactions were observed
      between the Mab against GlcCer and both amphotericin B (AmB) and itraconazole.
      Because Scedosporium species develop drug resistance, the number of available
      antifungal drugs is limited; our data indicate that combining immunotherapy with
      the available drugs might be a viable treatment option. These results suggest
      that in S. apiospermum, GlcCer are most likely cell wall components that are
      targeted by antifungal antibodies, which directly inhibit fungal development and
      enhance macrophage function; furthermore, these results suggest the combined use
      of monoclonal antibodies against GlcCer and antifungal drugs for antifungal
      immunotherapy. 

PMID- 24878574
TI  - Ethical issues in hospital clients' satisfaction: a Brazilian perspective.
AB  - BACKGROUND: Health institutions can be considered as complex organizations
      because they need to be prepared to receive and satisfy patients. This clientele
      differs from other organizations because the use of hospital services is not a
      matter of choice. Another motive for this difference is that, most often, the
      patients do not determine what services and products they will use during their
      stay. Although they are the clients, usually, health professionals decide which
      service or product they will consume. Hence, nursing care delivery based on
      competence, efficiency and ethics represents a challenge. OBJECTIVE: This
      critical reflection is meant to draw attention to the relevance of the ethical
      aspects of nurses' actions involving patients' satisfaction with nursing care.
      RESEARCH DESIGN: This paper highlights the responsibility of nurses to develop
      ethical actions in their commitment to manage and provide care with quality,
      commitment and efficiency. FINDINGS AND DISCUSSION: Possibilities of actions
      needed emerged from this discussion, such as the provision of reliable and
      updated information to clients, respect for standards, routines of care, exams
      and others, as well as clients' education, in order to further their involvement
      and participation in decisions concerning the care planned for them. CONCLUSION:
      The adoption of this paradigm entails a change in the performance of nurses'
      management and care roles, which may have to observe attitudes previously
      disregarded in most services provided.

PMID- 24878573
TI  - Nurses' professional values and attitudes toward collaboration with physicians.
AB  - BACKGROUND: Growing evidence suggests that collaborative practice improves
      healthcare outcomes, but the precursors to collaborative behavior between nurses
      and physicians have not been fully explored. RESEARCH QUESTION: The purpose of
      this descriptive correlational study was to describe the professional values held
      by nurses and their attitudes toward physician-nurse collaboration and to explore
      the relationships between nurses' characteristics (e.g. education, type of work)
      and professional values and their attitudes toward nurse-physician collaboration.
      RESEARCH DESIGN: This descriptive correlational study examines the relationship
      between nurses' professional values (Nurses Professional Values Scale-Revised)
      and their attitudes toward nurse-physician collaboration (Jefferson Scale of
      Attitudes toward Physician-Nurse Collaboration). ETHICAL CONSIDERATIONS:
      Permission to conduct the study was received from the hospital, and the
      Institutional Review Boards of the healthcare system and the participating
      university. PARTICIPANTS/CONTEXT: A convenience sample of 231 registered nurses
      from a tertiary hospital in the United States was surveyed. FINDINGS: A
      significant positive relationship was found between nurses' professional values
      and better attitudes toward collaboration with physicians (r = .26, p < .01).
      Attitude toward collaboration with physicians was also positively associated with
      master's or higher levels of education (F(3, 224) = 4.379, p = .005). DISCUSSION:
      The results of this study can be helpful to nurse administrators who are
      responsible for developing highly collaborative healthcare teams and for nurse
      educators who are focused on developing professional values in future nurses.

PMID- 24878575
TI  - Preference of Chinese general public and healthcare providers for a good death.
AB  - OBJECTIVES: The aim of this study is to find and compare the current situation
      between common people and healthcare providers' preferences for a good death in
      the context of Chinese culture. METHODS: A cross-sectional anonymous
      questionnaire survey covering 190 ordinary Chinese people and 323 healthcare
      providers was conducted. An inventory of the good death was translated and the
      subjects were surveyed about their attitude toward it. ETHICAL CONSIDERATIONS:
      Permission to conduct the study was granted by department chiefs, nurse managers
      and the participants themselves. The participants were informed that they took
      part on a voluntary and anonymous basis, that they could withdraw at any time,
      that they had the right to ignore questions they did not wish to answer, and that
      whatever they chose to do would not jeopardize their employment conditions.
      RESULTS: The attributes that were perceived as important by major respondents for
      a good death were maintaining hope and pleasure, good relationship with medical
      staff, good relationship with family, independence, environment comfort, being
      respected as an individual, preparation for death, physical and psychological
      comfort, dying in a favorite place, and not being a burden to others. And some
      relatively less important characteristics were life completion, receiving enough
      treatment, natural death, controlling over the future, unawareness of death,
      pride and beauty, feeling that one's life is worth living, and religious and
      spiritual comfort. We also found that healthcare providers were more likely than
      general out-patients to perceive "physical and psychological comfort," "dying in
      a favorite place," "good relationship with medical staff," and "natural death" as
      important for a good death. CONCLUSION: This study offers healthcare providers in
      China a fundamental understanding of the normal expectations of the general
      public for a good death. It is believed that these findings in our study are
      valuable to improve palliative care in China. We compared the attitudes of
      Chinese and Westerners and found some differences, which suggested that cultural
      difference should be an important consideration to achieve a good death in China.
      We also found that healthcare providers see good death differently from general
      public, indicating that the criteria for good death warrant further study.

PMID- 24878576
TI  - Severe nocturnal and postexercise hypoxia in children and adolescents with sickle
      cell disease.
AB  - Hypoxia is a common feature in children with sickle cell disease (SCD) that is
      inconsistently associated with painful crises and acute chest syndrome. To assess
      the prevalence and risk factors of hypoxia, we recorded daytime, nocturnal, and
      postexercise pulse oximetry (SpO2) values in 39 SCD patients with a median age of
      10.8 years. Median daytime SpO2 was 97% (range, 89%-100%), and 36% of patients
      had daytime hypoxia defined as SpO2<96%. Median nocturnal SpO2 was 94.7% (range,
      87.7%-99.5%), 50% of patients had nocturnal hypoxia defined as SpO2<=93%, and
      11(37%) patients spent more than 10% of their total sleep time with SpO2<90%.
      Median postexercise SpO2 was 94% (range, 72%-100%) and 44.7% of patients had
      postexercise hypoxia defined as an SpO2 decrease >=3% after a 6-minute walk test.
      Among patients with normal daytime SpO2, 35% had nocturnal and 42% postexercise
      hypoxia. Compared to 9 patients without daytime, nocturnal, or postexercise
      hypoxia, 25 patients with hypoxia under at least one of these three conditions
      had greater anemia severity (P = 0.01), lower HbF levels (P = 0.04), and higher
      aspartate aminotransferase levels (P = 0.03). Males predominated among patients
      with postexercise hypoxia (P = 0.004). Hypoxia correlated neither with painful
      crises nor with acute chest syndrome. Of 32 evaluable patients, 6 (18.8%) had a
      tricuspid regurgitation velocity >=2.6 m/s, and this feature was associated with
      anemia (P = 0.044). Median percentage of the predicted distance covered during a
      6-minute walk test was 86% [46-120]; the distance was negatively associated with
      LDH (P = 0.044) and with a past history of acute chest syndrome (P = 0.009). In
      conclusion, severe episodes of nocturnal and postexercise hypoxia are common in
      children with SCD, even those with normal daytime SpO2. 

PMID- 24878577
TI  - Altered formalin-induced pain and Fos induction in the periaqueductal grey of
      preadolescent rats following neonatal LPS exposure.
AB  - Animal and human studies have demonstrated that early pain experiences can
      produce alterations in the nociceptive systems later in life including increased
      sensitivity to mechanical, thermal, and chemical stimuli. However, less is known
      about the impact of neonatal immune challenge on future responses to noxious
      stimuli and the reactivity of neural substrates involved in analgesia. Here we
      demonstrate that rats exposed to Lipopolysaccharide (LPS; 0.05 mg/kg IP,
      Salmonella enteritidis) during postnatal day (PND) 3 and 5 displayed enhanced
      formalin-induced flinching but not licking following formalin injection at PND
      22. This LPS-induced hyperalgesia was accompanied by distinct recruitment of
      supra-spinal regions involved in analgesia as indicated by significantly
      attenuated Fos-protein induction in the rostral dorsal periaqueductal grey (DPAG)
      as well as rostral and caudal axes of the ventrolateral PAG (VLPAG). Formalin
      injections were associated with increased Fos-protein labelling in lateral
      habenula (LHb) as compared to medial habenula (MHb), however the intensity of
      this labelling did not differ as a result of neonatal immune challenge. These
      data highlight the importance of neonatal immune priming in programming
      inflammatory pain sensitivity later in development and highlight the PAG as a
      possible mediator of this process. 

PMID- 24878578
TI  - Evaluation of gastroepiploic arterial grafts to right coronary artery using
      transit-time flow measurement.
AB  - OBJECTIVES: The objective of this study was to analyse the relationship between
      the intraoperative transit-time flow measurement (TTFM) parameter values and the
      postoperative angiographic results of gastroepiploic arterial (GEA) grafts to the
      right coronary artery (RCA). We investigated whether the intraoperative TTFM
      parameter values are reliable indicators of early patency in GEA grafts to the
      RCA. METHODS: Patients undergoing off-pump coronary artery bypass surgery with
      GEA grafts were included in this study. Eighty-three GEA grafts were individually
      anastomosed and examined by angiography 1 week after surgery. The quality of each
      graft was graded using FitzGibbon grading (Study 1) and graft-flow grading (Study
      2). RESULTS: Study 1: Seventy-two grafts were determined as Grade A and 11 as
      Grades B or O. There were no significant differences in the average of mean graft
      flow (MGF), pulsatility index or diastolic filling percentage between Grade A and
      Grades B or O grafts. Study 2: Sixty-two grafts were graded as good-graft
      dominant, 16 as bidirectional and 5 as occlusion including string. The average of
      the MGF, pulsatility index and diastolic filling percentage in the grafts graded
      as bidirectional and occlusion including string were not significantly different
      from those of grafts graded as good-graft dominant. CONCLUSIONS: Previously
      reported cut-off values for intraoperative TTFM parameters could not be adapted
      for the early patency of GEA grafts to the RCA. However, the smoothness of the
      graft-flow curve may be a reliable predictor of postoperative graft patency.

PMID- 24878580
TI  - Cor triatriatum sinister.
AB  - The cor triatriatum sinister is an uncommon congenital cardiac anomaly and
      reports in the literature are limited. It is often associated with other cardiac
      malformations, such as atrial septal defect, transposition of the great arteries,
      tetralogy of Fallot or atrioventricular septal defect. We present here a 6-year
      old boy who was diagnosed with cor triatriatum sinister, initially showing
      symptoms similar to mitral valve stenosis and congestive heart failure, and who
      underwent subsequent surgical correction using a left atrial approach. The
      fibromuscular membrane, separating the pulmonary veins from the mitral valve, was
      completely resected and postoperative echocardiography showed unobstructed
      pulmonary venous flow. 

PMID- 24878579
TI  - Evaluation of a semi-quantitative ELISA for IgA antibody against Epstein-Barr
      virus capsid antigen in the serological diagnosis of nasopharyngeal carcinoma.
AB  - OBJECTIVES: This study was designed to establish an ELISA method, as well as the
      cut-off value, for IgA against Epstein-Barr virus (EBV) viral capsid antigen
      (VCA), as a screening assay for nasopharyngeal carcinoma (NPC) in southern China.
      In addition, the correlation between relative optical density (rOD) values from
      ELISA and titers from the immunoenzymatic assay (IEA) was also evaluated.
      METHODS: Two hundred and fifty-eight NPC cases, 33 non-NPC head and neck cancer
      patients, and 1156 healthy controls were recruited for this study. VCA-IgA and
      early antigen (EA)-IgA were measured by ELISA kits and IEA in parallel. RESULTS:
      The total precision of the VCA-IgA ELISA achieved a level of <13.0% coefficient
      of variation. An rOD value of 1.60 for the VCA-IgA ELISA was determined as the
      cut-off point for southern China, and the sensitivity and specificity for NPC
      diagnosis when using this cut-off value were 93.0% and 92.4%, respectively. The
      area under the receiver operating characteristic curve (ROC-AUC) value was 0.969.
      The correlation coefficient between titers and rOD values was 0.957. rOD values
      were correlated with NPC overall stage and lymph node involvement. CONCLUSIONS:
      The cut-off level established in our study could be used to facilitate more
      accurate diagnosis of NPC in southern China. The rOD value might be an index for
      NPC prognosis, since it shows a good correlation with the titer from IEA.

PMID- 24878582
TI  - Effects of cationic polyacrylamide characteristics on sewage sludge dewatering
      and moisture evaporation.
AB  - The effects of the molecular weight (MW) and charge density (CD) of cationic
      polyacrylamide (CPAM) on sludge dewatering and moisture evaporation were
      investigated in this study. Results indicated that in sludge conditioning, the
      optimum dosages were 10, 6, 6, 4, and 4 mg g(-1) CPAM with 5 million MW and 20%
      CD, 5 million MW and 40% CD, 3 million MW and 40% CD, 8 million MW and 40% CD,
      and 5 million MW and 60% CD, respectively. The optimum dosage of CPAM was
      negatively correlated with its CD or MW if the CD or MW of CPAM was above 20% or
      5 million. In the centrifugal dewatering of sludge, the moisture content in the
      conditioned sludge gradually decreased with the extension of centrifugation time,
      and the economical centrifugal force was 400*g. The moisture evaporation rates of
      the conditioned sludge were closely related to sludge dewaterability, which was
      in turn significantly correlated either positively with the solid content of
      sludge particles that were >2 mm in size or negatively with that of particles
      measuring 1 mm to 2 mm in diameter. During treatment, sludge moisture content was
      reduced from 80% to 20% by evaporation, and the moisture evaporation rates were
      1.35, 1.49, 1.62, and 2.24 times faster in the sludge conditioned using 4 mg g(
      1) CPAM with 5 million MW and 60% CD than in the sludge conditioned using 4 mg g(
      1) CPAM with 8 million MW and 40% CD, 6 mg g(-1) CPAM with 5 million MW and 40%
      CD, 6 mg g(-1) CPAM with 3 million MW and 40% CD, and 10 mg g(-1) CPAM with 5
      million MW and 20% CD, respectively. Hence, the CPAM with 5 million MW and 60% CD
      was ideal for sludge dewatering.

PMID- 24878583
TI  - Targeting immune suppression with PDE5 inhibition in end-stage multiple myeloma.
AB  - Myeloid-derived suppressor cells (MDSC) play a significant role in tumor-induced
      immune suppression. Targeting their function could improve antitumor therapies.
      Previously, we demonstrated that phosphodiesterase 5 (PDE5) inhibition in MDSCs
      augmented antitumor immunity in murine models. Here, we show how the addition of
      the PDE5 inhibitor, tadalafil, in a patient with end-stage relapsed/refractory
      multiple myeloma reduced MDSC function and generated a dramatic and durable
      antimyeloma immune and clinical response. Strategies targeting MDSC function with
      PDE5 inhibitors represent a novel approach that can augment the efficacy of tumor
      directed therapies.

PMID- 24878584
TI  - Is exercise used as medicine? Association of meeting strength training guidelines
      and functional limitations among older US adults.
AB  - OBJECTIVE: To determine the association between meeting strength training
      guidelines (>=2 times per week) and the presence of functional limitations among
      older adults. METHODS: This cross-sectional study used data from older adult
      participants (N=6763) of the National Health Interview Survey conducted in 2011
      in the United States. RESULTS: Overall, 16.1% of older adults reported meeting
      strength training guidelines. For each of nine functional limitations, those with
      the limitation were less likely to meet strength training recommendations than
      those without the limitation. For example, 20.0% of those who reported no
      difficulty walking one-quarter mile met strength training guidelines, versus only
      10.1% of those who reported difficulty (p<.001). In sum, 21.7% of those with no
      limitations (33.7% of sample) met strength training guidelines, versus only 15.9%
      of those reporting 1-4 limitations (38.5% of sample) and 9.8% of those reporting
      5-9 limitations (27.8% of sample) (p<.001). CONCLUSION: Strength training is
      uncommon among older adults and even less common among those who need it the
      most. The potential for strength training to improve the public's health is
      therefore substantial, as those who have the most to gain from strength training
      participate the least.

PMID- 24878585
TI  - Obesity treatment in disadvantaged population groups: where do we stand and what
      can we do?
AB  - Obesity is now the second leading cause of death and disease in the United States
      leading to health care expenditures exceeding $147 billion dollars. The
      socioeconomically disadvantaged and racial/ethnic minority groups are at
      significantly increased risk for obesity. Despite this, low income and minority
      individuals are underrepresented in the current obesity treatment literature.
      Additionally, weight loss outcomes for these high risk groups are well below what
      is typically produced in standard, well-controlled behavioral interventions and
      reach and access to treatment is often limited. The use of telecommunications
      technology may provide a solution to this dilemma by expanding dissemination and
      allowing for dynamic tailoring. Further gains may be achieved with the use of
      material incentives to enhance uptake of new behaviors. Regardless of what novel
      strategies are deployed, the need for further research to improve the health
      disparities associated with obesity in disadvantaged groups is critical. The
      purpose of this manuscript is to review the weight loss intervention literature
      that has targeted socioeconomically disadvantaged and racial/ethnic minority
      populations with an eye toward understanding outcomes, current limitations, areas
      for improvement and need for further research.

PMID- 24878587
TI  - The Intrapsychic and Interactional Realms: A Hermeneutic approach to Mental
      Space.
AB  - This paper addresses the tension between Freud's emphasis on the intrapsychic
      world and the emphasis placed by the Boston Change Process Study Group (BCPSG) on
      real interaction. Freud claimed that the intrapsychic world is primary; the BCPSG
      claim that interaction is primary. Both assume that these "levels" are discrete
      domains that can be isolated empirically, and that interact according to
      regulative rules in the natural world. This assumption reifies the metaphorical
      concept of mental space and freezes it at the metapsychological level of
      discourse. From a hermeneutic perspective, we must put these metaphorical
      concepts in dialogue with the context-specific processes of interpreting the
      patient's communication and intervening therapeutically. It then becomes clear
      that (1) the meaning of the terms "intrapsychic" and "interactive" is context
      sensitive; (2) the question of primacy is a pragmatic one that cannot be decided
      through metapsychological debate; (3) when we say that a behavior or mental
      process operates on the "intrapsychic" or "interactive" level, we are making a
      judgment call that is not based on reason (even if our judgment enlists reason in
      its support). These metapsychological constructs help us think about our
      experience with patients. However, their meaning exists largely as a potential
      and is never definitively determined.

PMID- 24878586
TI  - HIV incidence and risk factors in Chinese young men who have sex with men--a
      prospective cohort study.
AB  - OBJECTIVES: To assess HIV incidence and its associated risk factors among young
      men who have sex with men (YMSM) in urban areas, China. DESIGN: The study used a
      prospective cohort study design and standard diagnostic tests. METHODS: A twelve
      month prospective cohort study was conducted among YMSM (18-25 years old) in 8
      large cities in China. The participants were recruited via snowball sampling. A
      total of 1102 HIV-negative YMSM completed baseline assessment, 878 YMSM
      participants completed 6-month follow-up, and 902 completed 12-month follow-up.
      HIV was screened by an enzyme-linked immunosorbent assay and confirmed with
      Western Blot. Syphilis was screened via rapid plasma reagent and confirmed by
      treponema pallidum particle agglutination assay. RESULTS: 78 HIV seroconversions
      were identified within 1168.4 person-year observations yielding an incidence rate
      of 6.7 per 100 person-years. HIV seroconversion was associated with non-student
      status (RR = 2.61, 90% CI = 1.3-5.26), low HIV transmission knowledge (RR = 8.87,
      90% CI = 2.16-36.43), and syphilis infection (RR = 5.04, 90% CI = 2.57-9.90).
      CONCLUSIONS: Incidence of HIV among YMSM is high in urban areas of China.
      Interventions measures are required to contain the HIV epidemic within this
      population.

PMID- 24878588
TI  - Knockdown of the Rhipicephalus microplus cytochrome c oxidase subunit III gene is
      associated with a failure of Anaplasma marginale transmission.
AB  - Rhipicephalus microplus is an obligate hematophagous ectoparasite of cattle and
      an important biological vector of Anaplasma marginale in tropical and subtropical
      regions. The primary determinants for A. marginale transmission are infection of
      the tick gut, followed by infection of salivary glands. Transmission of A.
      marginale to cattle occurs via infected saliva delivered during tick feeding.
      Interference in colonization of either the tick gut or salivary glands can affect
      transmission of A. marginale to naive animals. In this study, we used the tick
      embryonic cell line BME26 to identify genes that are modulated in response to A.
      marginale infection. Suppression-subtractive hybridization libraries (SSH) were
      constructed, and five up-regulated genes {glutathione S-transferase (GST),
      cytochrome c oxidase sub III (COXIII), dynein (DYN), synaptobrevin (SYN) and
      phosphatidylinositol-3,4,5-triphosphate 3-phosphatase (PHOS)} were selected as
      targets for functional in vivo genomic analysis. RNA interference (RNAi) was used
      to determine the effect of tick gene knockdown on A. marginale acquisition and
      transmission. Although RNAi consistently knocked down all individually examined
      tick genes in infected tick guts and salivary glands, only the group of ticks
      injected with dsCOXIII failed to transmit A. marginale to naive calves. To our
      knowledge, this is the first report demonstrating that RNAi of a tick gene is
      associated with a failure of A. marginale transmission. 

PMID- 24878589
TI  - The effect of arm support combined with rehabilitation games on upper-extremity
      function in subacute stroke: a randomized controlled trial.
AB  - BACKGROUND: Use of rehabilitation technology, such as (electro)mechanical devices
      or robotics, could partly relieve the increasing strain on stroke rehabilitation
      caused by an increasing prevalence of stroke. Arm support (AS) training showed
      improvement of unsupported arm function in chronic stroke. OBJECTIVE: To examine
      the effect of weight-supported arm training combined with computerized exercises
      on arm function and capacity, compared with dose-matched conventional reach
      training in subacute stroke patients. METHODS: In a single-blind, multicenter,
      randomized controlled trial, 70 subacute stroke patients received 6 weeks of
      training with either an AS device combined with computerized exercises or dose
      matched conventional training (CON). Arm function was evaluated pretraining and
      posttraining by Fugl-Meyer assessment (FM), maximal reach distance, Stroke Upper
      Limb Capacity Scale (SULCS), and arm pain via Visual Analogue Scale, in addition
      to perceived motivation by Intrinsic Motivation Inventory posttraining. RESULTS:
      FM and SULCS scores and reach distance improved significantly within both groups.
      These improvements and experienced pain did not differ between groups. The AS
      group reported higher interest/enjoyment during training than the CON group.
      CONCLUSIONS: AS training with computerized exercises is as effective as
      conventional therapy dedicated to the arm to improve arm function and activity in
      subacute stroke rehabilitation, when applied at the same dose.

PMID- 24878591
TI  - Novel pseudo-wavelet function for MMG signal extraction during dynamic fatiguing
      contractions.
AB  - The purpose of this study was to develop an algorithm to classify muscle fatigue
      content in sports related scenarios. Mechanomyography (MMG) signals of the biceps
      muscle were recorded from thirteen subjects performing dynamic contractions until
      fatigue. For training and testing purposes, the signals were labeled in two
      classes (Non-Fatigue and Fatigue). A genetic algorithm was used to evolve a
      pseudo-wavelet function for optimizing the detection of muscle fatigue. Tuning of
      the generalized evolved pseudo-wavelet function was based on the decomposition of
      70% of the conducted MMG trials. After completing 25 independent pseudo-wavelet
      evolution runs, the best run was selected and then tested on the remaining 30% of
      the data to measure the classification performance. Results show that the evolved
      pseudo-wavelet improved the classification rate of muscle fatigue by 4.70
      percentage points to 16.61 percentage points when compared to other standard
      wavelet functions, giving an average correct classification of 80.63%, with
      statistical significance (p < 0.05).

PMID- 24878590
TI  - Aluminium induced endoplasmic reticulum stress mediated cell death in SH-SY5Y
      neuroblastoma cell line is independent of p53.
AB  - Aluminium (Al) is the third most abundant element in the earth's crust and its
      compounds are used in the form of house hold utensils, medicines and in
      antiperspirant etc. Increasing number of evidences suggest the involvement of
      Al+3 ions in a variety of neurodegenerative disorders including Alzheimer's
      disease. Here, we have attempted to investigate the role of Al in endoplasmic
      reticulum stress and the regulation of p53 during neuronal apoptosis using
      neuroblastoma cell line. We observed that Al caused oxidative stress by
      increasing ROS production and intracellular calcium levels together with
      depletion of intracellular GSH levels. We also studied modulation of key pro- and
      anti-apoptotic proteins and found significant alterations in the levels of Nrf2,
      NQO1, pAKT, p21, Bax, Bcl2, Abeta1-40 and Cyt c together with increase in
      endoplasmic reticulum (ER) stress related proteins like CHOP and caspase 12.
      However, with respect to the role of p53, we observed downregulation of its
      transcript as well as protein levels while analysis of its ubiquitination status
      revealed no significant changes. Not only did Al increase the activities of
      caspase 9, caspase 12 and caspase 3, but, by the use of peptide inhibitors of
      specific and pan-caspases, we observed significant protection against neuronal
      cell death upon inhibition of caspase 12, demonstrating the prominent role of
      endoplasmic reticulum stress generated responses in Al toxicity. Overall our
      findings suggest that Al induces ER stress and ROS generation which compromises
      the antioxidant defenses of neuronal cells thereby promoting neuronal apoptosis
      in p53 independent pathway. 

PMID- 24878592
TI  - A compact microelectrode array chip with multiple measuring sites for
      electrochemical applications.
AB  - In this paper we demonstrate the fabrication and electrochemical characterization
      of a microchip with 12 identical but individually addressable electrochemical
      measuring sites, each consisting of a set of interdigitated electrodes acting as
      a working electrode as well as two circular electrodes functioning as a counter
      and reference electrode in close proximity. The electrodes are made of gold on a
      silicon oxide substrate and are passivated by a silicon nitride membrane. A
      method for avoiding the creation of high edges at the electrodes (known as lift
      off ears) is presented. The microchip design is highly symmetric to accommodate
      easy electronic integration and provides space for microfluidic inlets and
      outlets for integrated custom-made microfluidic systems on top. 

PMID- 24878593
TI  - Audio-visual perception system for a humanoid robotic head.
AB  - One of the main issues within the field of social robotics is to endow robots
      with the ability to direct attention to people with whom they are interacting.
      Different approaches follow bio-inspired mechanisms, merging audio and visual
      cues to localize a person using multiple sensors. However, most of these fusion
      mechanisms have been used in fixed systems, such as those used in video
      conference rooms, and thus, they may incur difficulties when constrained to the
      sensors with which a robot can be equipped. Besides, within the scope of
      interactive autonomous robots, there is a lack in terms of evaluating the
      benefits of audio-visual attention mechanisms, compared to only audio or visual
      approaches, in real scenarios. Most of the tests conducted have been within
      controlled environments, at short distances and/or with off-line performance
      measurements. With the goal of demonstrating the benefit of fusing sensory
      information with a Bayes inference for interactive robotics, this paper presents
      a system for localizing a person by processing visual and audio data. Moreover,
      the performance of this system is evaluated and compared via considering the
      technical limitations of unimodal systems. The experiments show the promise of
      the proposed approach for the proactive detection and tracking of speakers in a
      human-robot interactive framework. 

PMID- 24878594
TI  - Anatomical variations in termination of the uncal vein and its clinical
      implications in cavernous sinus dural arteriovenous fistulas.
AB  - INTRODUCTION: The aim of the study was to investigate the variations in the uncal
      vein (UV) termination and its clinical implication in cavernous sinus dural
      arteriovenous fistulas (CSDAVFs). METHODS: Biplane cerebral angiography in 80
      patients (160 sides) with normal cerebral venous return (normal group) was
      reviewed with special interest in the termination of the UV. Frequency and types
      of uncal venous drainage from CSDAVFs in consecutive 26 patients were also
      analyzed. RESULTS: In the normal group, the UV was identified in 118 sides (74
      %). The UV terminated into cavernous sinus (CS) in 41 sides (34 %), the
      superficial middle cerebral vein (SMCV) in 58 sides (48 %), the laterocavernous
      sinus (LCS) in 15 sides (13 %), and the paracavernous sinus (PCS) in 4 sides (3
      %). Cerebral venous blood via the UV draining into the CS directly (n=41) or
      through the SMCV and/or the LCS (n=45) was observed in 86 sides (54 %). Uncal
      venous drainage from CSDAVFs was found in 13 patients (50 %). The CSDAVFs drained
      directly into the UV in two patients, drained via LCS into the UV in two
      patients, and drained through the SMCV into the UV in the remaining nine
      patients. All cases were successfully treated by transvenous embolization with
      special attention given to uncal venous drainage. CONCLUSION: There are several
      variations in UV termination according to the embryological development of the
      primitive tentorial sinus and the deep telencephalic vein. Careful attention
      should be paid to uncal venous drainage for the treatment of CSDAVFs.

PMID- 24878595
TI  - The recurrent artery of Heubner in routine selective cerebral angiography.
AB  - INTRODUCTION: Heubner's recurrent artery (RAH) in brain selective catheter
      angiograms (digital subtraction angiography, DSA) was evaluated. METHODS:
      Bilateral cerebral angiograms with antero-posterior, lateral and oblique frontal
      views were obtained in 100 neurological patients aged from 5 to 90 years. Site of
      origin, type of course and branching of the RAH were studied. Three groups were
      obtained: arteries with solely the horizontal segment visible, horizontal and
      vertical segments visible and horizontal and vertical with intraparenchymal
      branches visible. RESULTS: A total of 24 RAHs were recognised in 20 patients: 7
      arose from the A1, 5 from the anterior cerebral artery (ACA)-anterior
      communicating artery (Acom), 11 from the A2, whereas in 1 case, the segment of
      origin from the ACA could not be identified. Seventeen arteries arose from the
      lateral wall of the ACA and seven from the superior wall of the A1 segment of the
      ACA. The RAH was bilaterally seen in 3 patients and unilaterally in 17 with one
      double RAH. Five RAHs were visible only after contrast injection in the
      contralateral internal carotid artery. A horizontal segment was visible in 7
      arteries, a horizontal followed by a vertical segment without visible
      intraparenchymal branching pattern was seen in 6 and a horizontal and vertical
      segment with visible intraparenchymal branching pattern was seen in 11. In five,
      the artery made a half loop with an inferior-convex curve just before the
      vertical segment, and in two cases, a full loop was observed. CONCLUSION: The RAH
      was recognised in 12% of the hemispheres of the present series of neurological
      patients studied with DSA.

PMID- 24878597
TI  - Adaptive experiments with a multivariate Elo-type algorithm.
AB  - The present article introduces the multivariate Elo-type algorithm (META), which
      is inspired by the Elo rating system, a tool for the measurement of the
      performance of chess players. The META is intended for adaptive experiments with
      correlated traits. The relationship of the META to other existing procedures is
      explained, and useful variants and modifications are discussed. The META was
      investigated within three simulation studies. The gain in efficiency of the
      univariate Elo-type algorithm was compared to standard univariate procedures; the
      impact of using correlational information in the META was quantified; and the
      adaptability to learning and fatigue was investigated. Our results show that the
      META is a powerful tool to efficiently control task performance in a short time
      period and to assess correlated traits. The R code of the simulations, the
      implementation of the META in MATLAB, and an example of how to use the META in
      the context of neuroscience are provided in supplemental materials. 

PMID- 24878596
TI  - Ostracism Online: A social media ostracism paradigm.
AB  - We describe Ostracism Online, a novel, social media-based ostracism paradigm
      designed to (1) keep social interaction experimentally controlled, (2) provide
      researchers with the flexibility to manipulate the properties of the social
      situation to fit their research purposes, (3) be suitable for online data
      collection, (4) be convenient for studying subsequent within-group behavior, and
      (5) be ecologically valid. After collecting data online, we compared the
      Ostracism Online paradigm with the Cyberball paradigm (Williams & Jarvis Behavior
      Research Methods, 38, 174-180, 2006) on need-threat and mood questionnaire scores
      (van Beest & Williams Journal of Personality and Social Psychology 91, 918-928,
      2006). We also examined whether ostracized targets of either paradigm would be
      more likely to conform to their group members than if they had been included.
      Using a Bayesian analysis of variance to examine the individual effects of the
      different paradigms and to compare these effects across paradigms, we found
      analogous effects on need-threat and mood. Perhaps because we examined conformity
      to the ostracizers (rather than neutral sources), neither paradigm showed effects
      of ostracism on conformity. We conclude that Ostracism Online is a cost
      effective, easy to use, and ecologically valid research tool for studying the
      psychological and behavioral effects of ostracism. 

PMID- 24878598
TI  - Evaluation of the attention network test using vibrotactile stimulations.
AB  - We report a vibrotactile version of the attention network test (ANT)-the tactile
      ANT (T-ANT). It has been questioned whether attentional components are modality
      specific or not. The T-ANT explores alertness, orienting, cognitive control, and
      their relationships, similar to its visual counterpart, in the tactile modality.
      The unique features of the T-ANT are in utilizing stimuli on a single plane-the
      torso-and replacing the original imperative flanker task with a tactile Simon
      task. Subjects wore a waist belt mounted with two vibrotactile stimulators
      situated on the back and positioned to the right and left of the spinal column.
      They responded by pressing keys with their right or left hand in reaction to the
      type of vibrotactile stimulation (pulsed/continuous signal). On a single trial,
      an alerting tone was followed by a short tactile (informative/noninformative)
      peripheral cue and an imperative tactile Simon task target. The T-ANT was
      compared with a variant of the ANT in which the flanker task was replaced with a
      visual Simon task. Experimental data showed effects of orienting over control
      only when the peripheral cues were informative. In contrast to the visual task,
      interactions between alertness and control or alertness and orienting were not
      found in the tactile task. A possible rationale for these results is discussed.
      The T-ANT allows examination of attentional processes among patients with tactile
      attentional deficits and patients with eyesight deficits who cannot take part in
      visual tasks. Technological advancement would enable implementation of the T-ANT
      in brain-imaging studies. 

PMID- 24878599
TI  - Tagging frogs with passive integrated transponders causes disruption of the
      cutaneous bacterial community and proliferation of opportunistic fungi.
AB  - Symbiotic bacterial communities play a key role in protecting amphibians from
      infectious diseases including chytridiomycosis, caused by the pathogenic fungus
      Batrachochytrium dendrobatidis. Events that lead to the disruption of the
      bacterial community may have implications for the susceptibility of amphibians to
      such diseases. Amphibians are often marked both in the wild and in captivity for
      a variety of reasons, and although existing literature indicates that marking
      techniques have few negative effects, the response of cutaneous microbial
      communities has not yet been investigated. Here we determine the effects of
      passive integrated transponder (PIT) tagging on culturable cutaneous microbial
      communities of captive Morelet's tree frogs (Agalychnis moreletii) and assess the
      isolated bacterial strains for anti-B. dendrobatidis activity in vitro. We find
      that PIT tagging causes a major disruption to the bacterial community associated
      with the skin of frogs (~12-fold increase in abundance), as well as a concurrent
      proliferation in resident fungi (up to ~200-fold increase). Handling also caused
      a disruption the bacterial community, although to a lesser extent than PIT
      tagging. However, the effects of both tagging and handling were temporary, and
      after 2 weeks, the bacterial communities were similar to their original
      compositions. We also identify two bacterial strains that inhibit B.
      dendrobatidis, one of which increased in abundance on PIT-tagged frogs at 1 day
      postmarking, while the other was unaffected. These results show that PIT tagging
      has previously unobserved consequences for cutaneous microbial communities of
      frogs and may be particularly relevant for studies that intend to use PIT tagging
      to identify individuals involved in trials to develop probiotic treatments. 

PMID- 24878600
TI  - Biomineralization of uranium by PhoY phosphatase activity aids cell survival in
      Caulobacter crescentus.
AB  - Caulobacter crescentus is known to tolerate high levels of uranium [U(VI)], but
      its detoxification mechanism is poorly understood. Here we show that C.
      crescentus is able to facilitate U(VI) biomineralization through the formation of
      U-Pi precipitates via its native alkaline phosphatase activity. The U-Pi
      precipitates, deposited on the cell surface in the form of meta-autunite
      structures, have a lower U/Pi ratio than do chemically produced precipitates. The
      enzyme that is responsible for the phosphatase activity and thus the
      biomineralization process is identified as PhoY, a periplasmic alkaline
      phosphatase with broad substrate specificity. Furthermore, PhoY is shown to
      confer a survival advantage on C. crescentus toward U(VI) under both growth and
      nongrowth conditions. Results obtained in this study thus highlight U(VI)
      biomineralization as a resistance mechanism in microbes, which not only improves
      our understanding of bacterium-mineral interactions but also aids in defining
      potential ecological niches for metal-resistant bacteria. 

PMID- 24878601
TI  - Exposure of Bacillus subtilis to low pressure (5 kilopascals) induces several
      global regulons, including those involved in the SigB-mediated general stress
      response.
AB  - Studies of how microorganisms respond to pressure have been limited mostly to the
      extreme high pressures of the deep sea (i.e., the piezosphere). In contrast,
      despite the fact that the growth of most bacteria is inhibited at pressures below
      ~2.5 kPa, little is known of microbial responses to low pressure (LP). To study
      the global LP response, we performed transcription microarrays on Bacillus
      subtilis cells grown under normal atmospheric pressure (~101 kPa) and a nearly
      inhibitory LP (5 kPa), equivalent to the pressure found at an altitude of ~20 km.
      Microarray analysis revealed altered levels of 363 transcripts belonging to
      several global regulons (AbrB, CcpA, CodY, Fur, IolR, ResD, Rok, SigH, Spo0A).
      Notably, the highest number of upregulated genes, 86, belonged to the SigB
      mediated general stress response (GSR) regulon. Upregulation of the GSR by LP was
      confirmed by monitoring the expression of the SigB-dependent ctc-lacZ reporter
      fusion. Measuring transcriptome changes resulting from exposure of bacterial
      cells to LP reveals insights into cellular processes that may respond to LP
      exposure. 

PMID- 24878602
TI  - Indoor-biofilter growth and exposure to airborne chemicals drive similar changes
      in plant root bacterial communities.
AB  - Due to the long durations spent inside by many humans, indoor air quality has
      become a growing concern. Biofiltration has emerged as a potential mechanism to
      clean indoor air of harmful volatile organic compounds (VOCs), which are
      typically found at concentrations higher indoors than outdoors. Root-associated
      microbes are thought to drive the functioning of plant-based biofilters, or
      biowalls, converting VOCs into biomass, energy, and carbon dioxide, but little is
      known about the root microbial communities of such artificially grown plants, how
      or whether they differ from those of plants grown in soil, and whether any
      changes in composition are driven by VOCs. In this study, we investigated how
      bacterial communities on biofilter plant roots change over time and in response
      to VOC exposure. Through 16S rRNA amplicon sequencing, we compared root bacterial
      communities from soil-grown plants with those from two biowalls, while also
      comparing communities from roots exposed to clean versus VOC-laden air in a
      laboratory biofiltration system. The results showed differences in bacterial
      communities between soil-grown and biowall-grown plants and between bacterial
      communities from plant roots exposed to clean air and those from VOC-exposed
      plant roots. Both biowall-grown and VOC-exposed roots harbored enriched levels of
      bacteria from the genus Hyphomicrobium. Given their known capacities to break
      down aromatic and halogenated compounds, we hypothesize that these bacteria are
      important VOC degraders. While different strains of Hyphomicrobium proliferated
      in the two studied biowalls and our lab experiment, strains were shared across
      plant species, suggesting that a wide range of ornamental houseplants harbor
      similar microbes of potential use in living biofilters. 

PMID- 24878603
TI  - Plant-pathogenic oomycetes, Escherichia coli strains, and Salmonella spp.
      Frequently found in surface water used for irrigation of fruit and vegetable
      crops in New York State.
AB  - In the United States, surface water is commonly used to irrigate a variety of
      produce crops and can harbor pathogens responsible for food-borne illnesses and
      plant diseases. Understanding when pathogens infest water sources is valuable
      information for produce growers to improve the food safety and production of
      these crops. In this study, prevalence data along with regression tree analyses
      were used to correlate water quality parameters (pH, temperature, turbidity),
      irrigation site properties (source, the presence of livestock or fowl nearby),
      and precipitation data to the presence and concentrations of Escherichia coli,
      Salmonella spp., and hymexazol-insensitive (HIS) oomycetes (Phytophthora and
      Pythium spp.) in New York State surface waters. A total of 123 samples from 18
      sites across New York State were tested for E. coli and Salmonella spp., of which
      33% and 43% were positive, respectively. Additionally, 210 samples from 38 sites
      were tested for HIS oomycetes, and 88% were found to be positive, with 10 species
      of Phytophthora and 11 species of Pythium being identified from the samples.
      Regression analysis found no strong correlations between water quality
      parameters, site factors, or precipitation to the presence or concentration of E.
      coli in irrigation sources. For Salmonella, precipitation (<= 0.64 cm) 3 days
      before sampling was correlated to both presence and the highest counts. Analyses
      for oomycetes found creeks to have higher average counts than ponds, and higher
      turbidity levels were associated with higher oomycete counts. Overall,
      information gathered from this study can be used to better understand the food
      safety and plant pathogen risks of using surface water for irrigation.

PMID- 24878604
TI  - Alzheimer's disease: is a vaccine possible?
AB  - The cause of Alzheimer's disease is still unknown, but the disease is
      distinctively characterized by the accumulation of beta-amyloid plaques and
      neurofibrillary tangles in the brain. These features have become the primary
      focus of much of the research looking for new treatments for the disease,
      including immunotherapy and vaccines targeting beta-amyloid in the brain. Adverse
      effects observed in a clinical trial based on the beta-amyloid protein were
      attributed to the presence of the target antigen and emphasized the relevance of
      finding safer antigen candidates for active immunization. For this kind of
      approach, different vaccine formulations using DNA, peptide, and heterologous
      prime-boost immunization regimens have been proposed. Promising results are
      expected from different vaccine candidates encompassing B-cell epitopes of the
      beta-amyloid protein. In addition, recent results indicate that targeting another
      protein involved in the etiology of the disease has opened new perspectives for
      the effective prevention of the illness. Collectively, the evidence indicates
      that the idea of finding an effective vaccine for the control of Alzheimer's
      disease, although not without challenges, is a possibility. 

PMID- 24878605
TI  - Lentiviral-mediated RNAi targeting caspase-3 inhibits apoptosis induced by serum
      deprivation in rat endplate chondrocytes in vitro.
AB  - Current studies find that degenerated cartilage endplates (CEP) of vertebrae,
      with fewer diffusion areas, decrease nutrient supply and accelerate
      intervertebral disc degeneration. Many more apoptotic cells have been identified
      in degenerated than in normal endplates, and may be responsible for the
      degenerated grade. Previous findings suggest that inhibition of apoptosis is one
      possible approach to improve disc regeneration. It is postulated that inhibition
      of CEP cell apoptosis may be responsible for the regeneration of endplates.
      Caspase-3, involved in the execution phase of apoptosis, is a candidate for
      regulating the apoptotic process. In the present study, CEP cells were incubated
      in 1% fetal bovine serum. Activated caspases were detected to identify the
      apoptotic pathway, and apoptosis was quantified by flow cytometry. Lentiviral
      caspase-3 short hairpin RNA (shRNA) was employed to study its protective effects
      against serum deprivation. Silencing of caspase-3 expression was quantified by
      reverse transcription-polymerase chain reaction and Western blots, and inhibition
      of apoptosis was quantified by flow cytometry. Serum deprivation increased
      apoptosis of rat CEP cells through activation of a caspase cascade. Lentiviral
      caspase-3 shRNA was successfully transduced into CEP cells, and specifically
      silenced endogenous caspase-3 expression. Surviving cells were protected by the
      downregulation of caspase-3 expression and activation. Thus, lentiviral caspase-3
      shRNA-mediated RNAi successfully silenced endogenous caspase-3 expression,
      preventing inappropriate or premature apoptosis. 

PMID- 24878608
TI  - The reductive supercritical hydrothermal process, a novel synthesis method for
      cobalt nanoparticles: synthesis and investigation on the reaction mechanism.
AB  - Highly crystalline cobalt nanoparticles with low surface oxidation were
      synthesized by the reductive supercritical hydrothermal process in the
      temperature range from 340 to 420  degrees C. Under these reaction conditions,
      hydrogen generated from formic acid decomposition is maximally soluble in water,
      enabling the effective reduction of cobalt ions and cobalt oxide. The reaction
      mechanism was investigated by kinetic analysis on the formation of cobalt
      nanoparticles. This analysis assumed the first order irreversible reaction and
      two different types of shrinking core models (chemical reaction and inter
      diffusion dominated). According to the proposed reaction mechanism, cobalt
      monoxide is probably formed at the early reaction stage, where insufficient H2 is
      available, or under high temperature conditions. Moreover, cobalt monoxide
      influences the entire reaction rate. Thus, suppressing the formation and growth
      of cobalt monoxide is of primary importance in the optimal synthesis of cobalt
      nanoparticles by the reductive supercritical hydrothermal process. 

PMID- 24878606
TI  - Behavioral effects of endogenous or exogenous estradiol and progesterone on
      cocaine sensitization in female rats.
AB  - Cocaine sensitization is a marker for some facets of addiction, is greater in
      female rats, and may be influenced by their sex hormones. We compared the
      modulatory effects of endogenous or exogenous estradiol and progesterone on
      cocaine-induced behavioral sensitization in 106 female rats. Ovariectomized
      female rats received progesterone (0.5 mg/mL), estradiol (0.05 mg/mL),
      progesterone plus estradiol, or the oil vehicle. Sham-operated control females
      received oil. Control and acute subgroups received injections of saline, while
      the repeated group received cocaine (15 mg/kg, ip) for 8 days. After 10 days, the
      acute and repeated groups received a challenge dose of cocaine, after which
      locomotion and stereotypy were monitored. The estrous cycle phase was evaluated
      and blood was collected to verify hormone levels. Repeated cocaine treatment
      induced overall behavioral sensitization in female rats, with increased
      locomotion and stereotypies. In detailed analysis, ovariectomized rats showed no
      locomotor sensitization; however, the sensitization of stereotypies was
      maintained. Only females with endogenous estradiol and progesterone demonstrated
      increased locomotor activity after cocaine challenge. Estradiol replacement
      enhanced stereotyped behaviors after repeated cocaine administration. Cocaine
      sensitization of stereotyped behaviors in female rats was reduced after
      progesterone replacement, either alone or concomitant with estradiol. The
      behavioral responses (locomotion and stereotypy) to cocaine were affected
      differently, depending on whether the female hormones were of an endogenous or
      exogenous origin. Therefore, hormonal cycling appears to be an important factor
      in the sensitization of females. Although estradiol increases the risk of cocaine
      sensitization, progesterone warrants further study as a pharmacological treatment
      in the prevention of psychostimulant abuse. 

PMID- 24878609
TI  - Non-tumorigenic epithelial cells secrete MCP-1 and other cytokines that promote
      cell division in breast cancer cells by activating ERalpha via PI3K/Akt/mTOR
      signaling.
AB  - Efforts in understanding the role of the microenvironment in the development of
      breast cancer have focused on tumor-stroma cross-talk, but the possibility that
      normal epithelial cells might also play a role in tumor progression has received
      little attention. Here, we show that non-tumorigenic human mammary epithelial
      cells (MCF10A and HMEC) secrete factors able to enhance the proliferation of
      estrogen receptor alpha (ERalpha) positive breast cancer cells (MCF7 and T47D)
      and suppress their ability to undergo apoptosis. Conditioned medium (CM) derived
      from MCF10A and HMEC cells was capable of activating ERalpha in a hormone
      independent way, by phosphorylating ERalpha on Ser167. Co-exposure with PI3K and
      mTORC1 inhibitors significantly reduced the ERalpha Ser167 phosphorylation and
      suppressed the proliferation-enhancing effects of both 10A-CM and HMEC-CM on MCF7
      cells. We show that MCF10A and HMEC secrete numerous cytokines, among them MCP-1,
      which was one of the most prevalent. MCP-1 was shown to have a role in the
      effects elicited by the 10A-CM. It activated the ERalpha by phosphorylating
      Ser167 via the PI3K/Akt/mTORC1 signaling pathway, an effect which was further
      confirmed by silencing the MCP-1 receptors, CCR2 and CCR4. To our knowledge, this
      is the first time MCP-1 has been shown to contribute to ERalpha signaling
      activation. These data suggest that normal mammary cells could have the
      capability of supporting the proliferation of breast cancer cells via paracrine
      interactions. A better understanding of the role of these cells may be useful for
      designing strategies for the prevention of tumor progression at early stages. 

PMID- 24878607
TI  - Hippocampal subfields differentially correlate with chronic pain in older adults.
AB  - Although previous studies have demonstrated that the hippocampus plays a role in
      pain processing, the role of hippocampal subfields is uncertain. The goal of this
      study was to examine the relationship between hippocampal subfield volumes and
      chronic pain in nondemented older adults. The study sample included 86 community
      residing adults age 70 or older who were free of dementia and recruited from the
      Einstein Aging Study. Chronic pain was defined as pain over the last 3 months,
      that was moderate or severe (minimum rating of 4 out of 10) most, or all of the
      time. Hippocampal subfield volumes were estimated using FreeSurfer software. We
      modeled the association between chronic pain and hippocampal and subfield volume
      using linear regression. The sample had a mean age of 80 and was 58% female.
      Chronic pain, present in 55% of the sample, was associated with smaller right and
      total hippocampal volumes, particularly in women, after adjusting for age,
      education, and intracranial volume (eTICV). In addition, in women, volume was
      significantly reduced in participants with chronic pain in right CA2-3 (beta=
      0.35, p=0.010), right CA4-DG (beta=-0.35, p=0.011), left presubiculum (beta=
      0.29, p=0.030), and left fimbria (beta=-0.30, p=0.023). In men, chronic pain was
      not associated with the volume of any of the hippocampal subfield volumes.
      Chronic pain in women is associated with a reduction in the volume of right
      hippocampus and also selected hippocampal subfields. Future studies should
      clarify the mechanisms underlying the association between regional hippocampal
      volumes and chronic pain, particularly in women. 

PMID- 24878610
TI  - Stromal cell derived factor-2 (Sdf2): a novel protein expressed in mouse.
AB  - The stromal derived factor (SDFs) family comprises a group of molecules generated
      by stromal cells. SDF1 and SDF4 are chemokines; SDF2 and SDF5 are not yet
      functionally and structurally defined. In human and mouse, Sdf2 has a paralogous
      gene, Sdf2l1, whose protein sequences are 78% similar and 68% identical. Human
      SDF2L1 is an endoplasmic reticulum-stress inducible-gene. In Arabidopsis
      thaliana, SDF2-like (39% and 37% amino acid sequence identity with Mus musculus
      Sdf2 and Sdf2l1) has also been implicated in activating the UPR in ER-stress.
      Here we have cloned, expressed and purified recombinant Sdf2 and raised an anti
      Sdf2 antibody. We demonstrated that the protein is expressed in several tissues
      and is localized in the endoplasmic reticulum. We suggest that Sdf2, initially
      predicted as a secretory protein because it lacks the canonical ER retention
      signals in its C-terminal, could be ER-resident through accessory binding
      proteins or other amino acid sequence motifs, as suggested for the homolog
      protein SDF2-like. Furthermore, the crystal structure of SDF2-like from
      Arabidopsis thaliana is a typical beta-trefoil containing three MIR motifs; all
      hydrophobic residues considered important for maintaining the bottom layer of the
      beta-trefoil barrel seem to be conserved in the Sdf2 family. Multiple alignment
      using 43 sequences for SDF2 and 38 for SDF2L1 paralogous families also revealed a
      very similar residue conservation profile. Comparing the amino acid sequence and
      predicted 3D structure with other Sdf2-like proteins we suggest a role of mouse
      Sdf2 in the Unfolded Protein Response and ER-stress, similar to that of Sdf2l1
      from human and mouse and SDF2-like from Arabidopsis thaliana. Chronic ER stress
      has been associated with many human diseases including cancer and diabetes.
      Identification of new factors associated with the ER stress pathway can help to
      identify and define key targets of this response. 

PMID- 24878611
TI  - Microparticles released by vascular endothelial cells increase hypoxia inducible
      factor expression in human proximal tubular HK-2 cells.
AB  - Microparticles are produced by vesiculation of the cell plasma membrane and serve
      as vectors of cell-to-cell communication. Co-culture experiments have shown that
      hypoxia-inducible factor-alpha (HIF-alpha)-regulated-genes are up-regulated in
      human renal proximal tubular HK-2 cells by endothelial cell factors which might
      be transported inside endothelial microparticles (EMP). Here we aimed to study in
      HK-2 cells the effect of EMP, produced by activated endothelial cells, on HIF
      alpha and HIF-alpha-regulated vascular endothelial growth factor-A (VEGF-A). EMP,
      at a concentration much lower than that found in plasma, increased the expression
      of HIF-alpha/VEGF-A in a COX-2/EP2 receptor dependent manner. Since the EMP/cells
      ratio was ~1/1000, we hypothesized that paracrine mediators produced by HK-2
      cells amplified the initial signal. This hypothesis was confirmed by two facts
      which also suggested that the mediators were conveyed by particles released by HK
      2 cells: (i) HIF-alpha was up-regulated in HK-2 cells treated with the pellet
      obtained from the conditioned medium of the EMP-treated HK-2 cells. (ii) In
      transwell experiments, EMP-treated cells increased the expression of HIF-alpha in
      untreated HK-2 cells. Interestingly, we detected these cells, particles that were
      released by EMP-treated HK-2 cells. Depending on the pathological context,
      activation of HIF-alpha and VEGF-A signaling in renal tissue/cells may have
      either beneficial or harmful effects. Therefore, our results suggest that their
      presence in the urinary space of EMP produced by activated endothelial cells may
      influence the outcome of a number of renal diseases. 

PMID- 24878614
TI  - Barriers to accessing HIV services for Black African communities in
      Cambridgeshire, the United Kingdom.
AB  - The majority of new HIV diagnoses in the United Kingdom (UK) occur in people with
      heterosexually acquired HIV infection, the majority of whom are African
      communities. Current research shows that despite health promotion efforts and
      advances in therapy these communities are accessing HIV care late. This study
      therefore explored barriers to equal access to HIV services by African migrants
      in the UK. Kleinman's (Patients and healers in the context of culture: an
      exploration of the borderland between anthropology, medicine, and psychiatry, vol
      3. University of California Press, Berkeley, 1980) model of health care systems
      was applied in this research as a theoretical framework and lens through which
      the reported findings are viewed as it places health within the broader context
      of culture. In this research a qualitative approach with focus groups was used. A
      total of thirty participants were recruited from African migrant community
      organisations in Cambridgeshire in the East of England strategic health authority
      in order to study the experiences of African migrants when accessing sexual
      health services. It was found that barriers to equal access to HIV services exist
      for African communities in Cambridgeshire. These included language barriers and
      others bordering on the use of traditional medicine by African migrants,
      understanding of cultural diversity, awareness of how and where to access HIV
      services, and getting information about HIV. Findings highlighted the importance
      of taking the sectors of Kleinman's [1] model into consideration when planning
      HIV services for African communities. 

PMID- 24878612
TI  - Comparison of health-related quality of life of patients with different precancer
      and oral cancer stages.
AB  - OBJECTIVES: Health-related quality of life (HR-QoL) informations are becoming an
      important tool for the treatment concept for cancer patients. The purpose of this
      study was to evaluate how the quality of life depends on the disease severity of
      pre- and oral cancer patients and which factors influence their quality of life.
      MATERIALS AND METHODS: During this study, 106 patients with a premalignant oral
      lesion, 174 patients with oral squamous cell carcinoma (OSSC) as well as 21
      patients with a recurrence of OSSC were asked about their oral health-related
      quality of life. Additionally, the UW-QOLv4 was used to record the psychological
      and clinical symptoms from which the patients of the three groups are suffering.
      RESULTS: Significant differences with respect to oral HR-QoL of life between the
      groups could be evaluated. Patients with a recurrence have the lowest and
      patients with precancer the highest HR-QoL. Within the groups, there is a
      difference regarding the significance of the psychological factors. The lowest
      values were achieved for mood within all three groups. Anxiety is of key
      importance for the precancer group whereas appearance and activity are of
      importance for the patients having a tumor. The patients of the recurrence group
      are heavily affected by all factors. CONCLUSIONS: The quality of life differs
      depending on the disease. The patients of the recurrence group have the lowest
      oral health-related quality of life for all aspects analyzed, and they are
      suffering the most with respect to the psychological dimensions of the UW-QOLv4.
      CLINICAL RELEVANCE: The present study examined the quality of life depending on
      the severity of the disease of pre- and oral cancer patients and which factors
      significantly influenced their quality of life. The evaluated findings of
      relevant variables may have therapeutic relevance for the multidisciplinary
      treatment of oral cancer patients in the future.

PMID- 24878613
TI  - Prevalence and demographic correlates of overweight and obesity among children in
      a transitional southeastern European population.
AB  - Our aim was to assess the prevalence and demographic correlates of overweight and
      obesity among children in Albania, a transitional country in Southeastern Europe.
      A nationwide survey was conducted in Albania in 2013 including a representative
      sample of 5,810 schoolchildren aged 7.0-9.9 years (51.5 % boys aged 8.5 +/- 0.6
      years and 49.5 % girls aged 8.4 +/- 0.6 years; overall response: 97 %). All
      children were measured height and weight, based on which the body mass index
      (BMI) was calculated. The criteria of the World Health Organization (WHO) and the
      International Obesity Task Force (IOTF) were used to describe the distribution of
      BMI among children. Overall, mean value of BMI was 16.4 +/- 2.4 (16.7 +/- 2.5 in
      boys vs. 16.2 +/- 2.4 in girls, P < 0.001). As per WHO criteria, 9.8 % of the
      boys were obese versus 5.5 % of the girls (P < 0.001). The prevalence of both
      overweight and obesity were remarkably higher among urban children compared with
      their rural counterparts (17.9 vs. 10.5 and 11.9 vs. 4.0 %, respectively, P <
      0.001). As per IOTF criteria, 3.8 % of the boys were obese compared with 2.8 % of
      the girls (P < 0.001). The prevalence of overweight and obesity were similarly
      higher among urban children than in rural children (15.6 vs. 7.3 and 5.5 vs. 1.4
      %, respectively, P < 0.001). Our findings indicate that Albania is in the middle
      of nutritional transition with a high prevalence of overweight and obesity among
      children aged 7.0-9.9 years. This is particularly evident in urban areas of the
      country. Conversely, our data do not indicate a double burden of malnutrition
      among children in Albania.

PMID- 24878615
TI  - Dispersion assessment in the location of facial landmarks on photographs.
AB  - The morphological assessment of facial features using photographs has played an
      important role in forensic anthropology. The analysis of anthropometric landmarks
      for determining facial dimensions and angles has been considered in diverse
      forensic areas. Hence, the quantification of the error associated to the location
      of facial landmarks seems to be necessary when photographs become a key element
      of the forensic procedure. In this work, we statistically evaluate the inter- and
      intra-observer dispersions related to the facial landmark identification on
      photographs. In the inter-observer experiment, a set of 18 facial landmarks was
      provided to 39 operators. They were requested to mark only those that they could
      precisely place on 10 photographs with different poses (frontal, oblique, and
      lateral views). The frequency of landmark location was studied together with
      their dispersion. Regarding the intra-observer evaluation, three participants
      identified 13 facial points on five photographs classified in the frontal and
      oblique views. Each landmark location was repeated five times at intervals of at
      least 24 h. The frequency results reveal that glabella, nasion, subnasale,
      labiale superius, and pogonion obtained the highest location frequency in the
      three image categories. On the contrary, the lowest rate corresponds to labiale
      inferius and menton. Meanwhile, zygia, gonia, and gnathion were significantly
      more difficult to locate than other facial landmarks. They produced a significant
      effect on the dispersion depending on the pose of the image where they were
      placed, regardless of the type of observer that positioned them. In particular,
      zygia and gonia presented a statistically greater variation in the three image
      poses, while the location of gnathion is less precise in oblique view
      photographs. Hence, our findings suggest that the latter landmarks tend to be
      highly variable when determining their exact position.

PMID- 24878617
TI  - Estimation of the pre-burning condition of human remains in forensic contexts.
AB  - The determination of the original condition of human remains prior to burning is
      critical since it may facilitate the reconstruction of circumstances surrounding
      death in forensic cases. Although the use of heat-induced bone changes is not a
      completely reliable proxy for determining pre-burning conditions, it is not
      completely devoid of potential, as we can observe a clear difference in the
      occurrence of such features between the fleshed and dry bones. In order to
      quantify this difference and determine its true value for forensic research, the
      frequencies of heat-induced warping and thumbnail fractures were documented on
      modern cremations of cadavers from recently deceased individuals and from the
      cremations of skeletons previously inhumed. The effect of age, sex, time span
      from death to cremation, duration and temperature of combustion on those
      frequencies was statistically investigated. Results demonstrated that the heat
      induced features were significantly more frequent in the sample of cadavers. In
      addition, warping was determined to be the most useful indicator of the pre
      burning condition of human remains. Temperature of combustion was the only
      variable having a significant effect on the frequency of both features,
      suggesting that fluctuation of temperature, along with collagen preservation and
      recrystallization of the inorganic phase, is paramount for their occurrence. Both
      warping and thumbnail fractures may eventually be used for the estimation of the
      pre-burning condition of human remains in lack of other indicators, but their
      reliability is far from absolute. Ideally, such inference must be supported by
      other data such as skeletal representation, objects or defleshing marks on the
      bones. 

PMID- 24878616
TI  - Association between Y haplogroups and autosomal AIMs reveals intra-population
      substructure in Bolivian populations.
AB  - For the correct evaluation of the weight of genetic evidence in a forensic
      context, databases must reflect the structure of the population, with all
      possible groups being represented. Countries with a recent history of admixture
      between strongly differentiated populations are usually highly heterogeneous and
      sub-structured. Bolivia is one of these countries, with a high diversity of
      ethnic groups and different levels of admixture (among Native Americans,
      Europeans and Africans) across the territory. For a better characterization of
      the male lineages in Bolivia, 17 Y-STR and 42 Y-SNP loci were genotyped in
      samples from La Paz and Chuquisaca. Only European and Native American Y
      haplogroups were detected, and no sub-Saharan African chromosomes were found.
      Significant differences were observed between the two samples, with a higher
      frequency of European lineages in Chuquisaca than in La Paz. A sample belonging
      to haplogroup Q1a3a1a1-M19 was detected in La Paz, in a haplotype background
      different from those previously found in Argentina. This result supports an old
      M19 North-south dispersion in South America, possibly via two routes. When
      comparing the ancestry of each individual assessed through his Y chromosome with
      the one estimated using autosomal AIMs, (a) increased European ancestry in
      individuals with European Y chromosomes and (b) higher Native American ancestry
      in the carriers of Native American Y-haplogroups were observed, revealing an
      association between autosomal and Y-chromosomal markers. The results of this
      study demonstrate that a sub-structure does exist in Bolivia at both inter- and
      intrapopulation levels, a fact which must be taken into account in the evaluation
      of forensic genetic evidence. 

PMID- 24878618
TI  - Identifying predictive factors for posttransplant lymphoproliferative disease in
      pediatric solid organ transplant recipients with Epstein-Barr virus viremia.
AB  - Epstein-Barr virus (EBV) viremia (EV) in pediatric solid organ transplant (SOT)
      recipients is a significant risk factor for posttransplant lymphoproliferative
      disease (PTLD) but not all patients with EV develop PTLD. We identify predictive
      factors for PTLD in patients with EV. We conducted a retrospective chart review
      of all pediatric SOT recipients (0 to 21 y) at a single institution between 2001
      and 2009. A total of 350 pediatric patients received a SOT and 90 (25.7%)
      developed EV. Of EV patients, 28 (31%) developed PTLD. The median age at
      transplant was 11.5 months in the PTLD group and 21.5 months in the EV-only group
      (P=0.003). Twenty-three (37%) EV-only patients had immunosuppression increased
      before EV, compared with 28 (100%) of PTLD patients (P<0.001). The median peak
      EBV level was 3212 EBV copies/10 lymphocytes for EV-only and 8392.5 EBV copies/10
      lymphocytes for PTLD (P=0.005). All patients who developed PTLD had >=1 clinical
      symptoms. Younger age at transplant, increased immunosuppression before EV,
      higher peak EBV level, and presence of clinical symptoms have predictive value in
      the development of PTLD in SOT patients with EV. 

PMID- 24878619
TI  - Ceftriaxone-induced hemolytic anemia: case report and review of literature.
AB  - Ceftriaxone is a frequently used empiric antibiotic in children. Acute hemolysis
      is a rare side effect of ceftriaxone therapy associated with a high mortality
      rate. A 14-year-old boy suffering from Crohn disease developed bacterial
      pneumonia that was treated with ceftriaxone. We report successful management of
      ceftriaxone-induced hemolytic anemia (CIHA) in this patient and review the CIHA
      literature in pediatric patients. Early recognition of CIHA with prompt
      discontinuation of ceftriaxone therapy may have a beneficial role in reduction of
      high mortality seen in these patients.

PMID- 24878620
TI  - Prechemotherapy robotic-assisted laparoscopic radical nephrectomy for an
      adolescent with Wilms tumor.
AB  - Although Wilms tumor (WT) is the most common pediatric renal tumor, adolescent
      and adult WT is rare. Nevertheless, adolescent renal tumors as a group are
      sufficiently uncommon that WT must be included in the differential diagnosis for
      such patients, and in doing so affects the oncologic considerations of the
      surgery. Herein, we describe a 14-year-old female presenting with a 1-month
      history of right flank pain. Subsequent work-up revealed a localized, centrally
      located, enhancing right renal mass. The patient underwent robotic-assisted
      laparoscopic radical nephrectomy and pathology demonstrated stage II, favorable
      histology WT. Herein, we will discuss the pertinent details regarding adolescents
      with renal tumors and the risks and benefits of using a minimally invasive
      surgical approach. 

PMID- 24878621
TI  - More on osteosarcoma and phylloides tumor.

PMID- 24878622
TI  - Analytical methods for soluble microbial products (SMP) and extracellular
      polymers (ECP) in wastewater treatment systems: a review.
AB  - Effluents from biological processes contain a wide range of complex organic
      compounds, including soluble microbial products (SMP) and extracellular polymers
      (ECP), released during bacteria metabolism in mixed culture in bioreactors. It is
      important to clearly identify the primary components of SMPs and ECPs in order to
      understand the fundamental mechanisms of biological activity that create these
      compounds, and how to reduce these compounds in the effluent. In addition, these
      compounds constitute the main foulants in membrane bioreactors which are being
      used more widely around the world. A review on the extraction of ECP,
      characterization, and identification of SMPs and ECPs is presented, and we
      summarize up-to-date pretreatments and analytical methods for SMPs. Most
      researchers have focused more on the overall properties of SMPs and ECPs such as
      their concentrations, molecular weight distribution, aromaticity, hydrophobic and
      hydrophilic properties, biodegradability, and toxicity characteristics. Many
      studies on the identification of effluent SMPs show that most of these compounds
      were not present in the influent, such as humic acids, polysaccharides, proteins,
      nucleic acids, organic acids, amino acids, exocellular enzymes, structural
      components of cells and products of energy metabolism. A few groups of
      researchers have been working on the identification of compounds in SMPs using
      advanced analytical techniques such as GC-MS, LC-IT-TOF-MS and MALDI-TOF-MS.
      However, there is still considerably more work needed to be done analytically to
      fully understand the chemical characteristics of SMPs and ECPs. 

PMID- 24878623
TI  - Surgical management of meningioma of the trigone area of the lateral ventricle.
AB  - OBJECTIVE: Lateral ventricular trigone meningioma is relatively rare and surgical
      resection is the main treatment strategy. It is a challenge to achieve total
      resection without any complication. We analyzed a series of cases using
      literature review. METHODS: Retrospective data was collected on patients who
      underwent surgical treatment for trigone meningioma at our department from 2007
      to 2012. RESULTS: Forty-three patients were included (12 men, 31 women). The
      average age was 42.8 years old. The symptoms depended on tumor size and location;
      38 had prominent symptoms. The preoperative neuroimaging help assess the entity,
      size, location, and blood supply of the tumor. All lesions were resected using
      the trans-sulcal temporal or parietal approach, with intraoperative ultrasound
      assistance. Total resection was achieved in all patients. Thirty-six patients had
      a ventricular drain, which was removed 1 to 14 days later. Of the patients having
      prominent symptoms, 31 had relief soon after the operation, the other 7 patients
      improved to some extent at long-term follow-up. Two patients developed
      intraoperative distant epidural hematoma, which was confirmed by ultrasound, and
      underwent hematoma evacuation immediately. Two patients were reoperated for
      extensive intracranial hypertension. Three patients developed localized
      hydrocephalus and 2 of those underwent ventriculoperitoneal shunt several months
      later and 1 patient had spontaneous relief. One patient had grade II meningioma
      and 2 had grade III; they underwent adjuvant radiotherapy. The follow-up period
      ranged from 2 to 71 months, with no recurrence. CONCLUSIONS: Surgical resection,
      using the trans-sulcal approach with intraoperative ultrasound assistance, can
      achieve a high rate of total resection and a low rate of complication, promising
      a good prognosis. The management technique and the perioperative treatment have
      to be individualized.

PMID- 24878624
TI  - Navigated high frequency ultrasound: description of technique and clinical
      comparison with conventional intracranial ultrasound.
AB  - OBJECTIVE: Conventional curved or sector array ultrasound (cioUS) is the most
      commonly used intraoperative imaging modality worldwide. Although highly
      beneficial in various clinical applications, at present the impact of linear
      array intraoperative ultrasound (lioUS) has not been assessed for intracranial
      use. We provide a technical description to integrate an independent lioUS probe
      into a commercially available neuronavigation system and evaluate the use of
      navigated lioUS as a resection control in glioblastoma surgery. METHODS: We
      performed a prospective study assessing residual tumor detection after complete
      microsurgical resection using either cioUS or lioUS in 15 consecutive patients.
      We compared the imaging findings of both ultrasound modalities in 44 sites
      surrounding the resection cavity. The respective findings were correlated with
      the histopathologic findings of tissue specimen obtained from those sites.
      RESULTS: Use of cioUS leaded to an additional resection in 9 patients, whereas
      lioUS detected residual tumor during all surgeries. A further resection was
      performed at 33 of 44 intraoperative sites (75%) based on results of lioUS alone.
      Resected tissue was solid tumor in 66% and infiltration zone in 34%. No false
      positive or false-negative findings were seen using lioUS. There was no case of a
      tumor detection in cioUS combined with a negative finding in lioUS. The
      difference of imaging results between cioUS and lioUS was significant (sign test,
      P<0.001). CONCLUSIONS: lioUS can be used as a safe and precise tool for
      intracranial image-guided resection control of glioblastomas. It can be
      integrated in a commercially available navigation system and shows a significant
      higher detection rate of residual tumor compared with conventional cioUS.

PMID- 24878625
TI  - Development and psychometric evaluation of the "Neurosurgical Evaluation of
      Attitudes towards simulation Training" (NEAT) tool for use in neurosurgical
      education and training.
AB  - OBJECTIVE: Neurosurgical simulation training is becoming increasingly popular.
      Attitudes toward simulation among residents can contribute to the effectiveness
      of simulation training, but such attitudes remain poorly explored in neurosurgery
      with no psychometrically proven measure in the literature. The aim of the present
      study was to evaluate prospectively a newly developed tool for this purpose: the
      Neurosurgical Evaluation of Attitudes towards simulation Training (NEAT).
      METHODS: The NEAT tool was prospectively developed in 2 stages and
      psychometrically evaluated (validity and reliability) in 2 administrations with
      the same participants. The tool comprises a questionnaire with 9 Likert scale
      items and 2 free-text sections assessing attitudes toward simulation in
      neurosurgery. RESULTS: The evaluation was completed with 31 neurosurgery
      residents in London, United Kingdom, who were generally favorable toward
      neurosurgical simulation. The internal consistency of the questionnaire was high,
      as demonstrated by the overall Cronbach alpha values (alpha=0.899 and
      alpha=0.955). All but 2 questionnaire items had "substantial" or "almost perfect"
      test-retest reliability following repeated survey administrations (median Pearson
      r correlation=0.688; range, 0.248-0.841). NEAT items were well correlated with
      each other on both occasions, showing good validity of content within the NEAT
      tool. There was no significant relationship between either gender or length of
      neurosurgical experience and item ratings. CONCLUSIONS: NEAT is the first
      psychometrically evaluated tool for evaluating attitudes toward simulation in
      neurosurgery. Further implementation of NEAT is required in wider neurosurgical
      populations to establish whether specific population groups differ. Use of NEAT
      in studies of neurosurgical simulation could offer an additional outcome measure
      to performance metrics, permitting evaluation of the impact of neurosurgical
      simulation on attitudes toward simulation both between participants and within
      the same participants over time.

PMID- 24878627
TI  - Upregulated expression of ebp1 contributes to schwann cell differentiation and
      migration after sciatic nerve crush.
AB  - Ebp1, an ErbB3-binding protein, is the human homologue of the cell cycle
      regulated mouse protein p38-2G4. Ebp1 was reported to inhibit the proliferation
      and induce the differentiation of human cancer cells. Its p48 isoform contributes
      to neuronal differentiation and growth factor specificity. However, the
      expression and role of Ebp1 in peripheral system lesions and repair are still
      unknown. Herein, we investigated the spatiotemporal pattern of Ebp1 expression
      following sciatic nerve crush. After crush, the level of Ebp1 protein was
      elevated gradually, peaked at day 5, and then declined to the normal at 4 weeks,
      which was similar to the expression of Oct-6. Furthermore, using double
      immunofluorescent staining, we found Ebp1 had a colocalization with S100 and Oct
      6 in 5-day injured tissues. In vitro, we observed enhanced expression of Ebp1
      during the process of cyclic adenosine monophosphate (cAMP)-induced Schwann cells
      differentiation. Interestingly, Ebp1-depleted SCs did not show significant
      morphologic change after the treatment of cAMP. Also, we observed a
      colocalization between Ebp1 and Cyclin D1 and that Ebp1-specific siRNA
      transfected SCs had a decreased migration. Taken together, we speculated that
      Ebp1 was upregulated in the sciatic nerve after crush, which was involved in the
      differentiation and migration of Schwann cells. 

PMID- 24878628
TI  - The expression changes of myelin and lymphocyte protein (MAL) following optic
      nerve crush in adult rats retinal ganglion cells.
AB  - Myelin and lymphocyte protein (MAL), a component of compact myelin, is highly
      expressed in oligodendrocytes and Schwann cells. It has been reported that MAL
      may play a vital role in the process of neuronal apoptosis following acute spinal
      cord injury. However, acquaintance regarding its distribution and possible
      function in the retina is limited. Therefore, in a rodent model of optic nerve
      crush (ONC), the dynamic changes of MAL in retina was detected. The expression of
      MAL was mainly located in the retinal ganglion cells (RGCs) and was increased
      strongly after ONC. The peak of MAL expression appeared on the third day. In
      addition, there was a concomitant upregulation of active-caspase-3, which also co
      localized with MAL in RGCs. Moreover, co-localization of MAL with terminal
      deoxynucleotidyl transferase-mediated biotinylated-dUTP nick-end labeling (TUNEL)
      was detected in RGCs after ONC. Collectively, all these results suggested that
      the upregulation of MAL might play an important role in the pathophysiology of
      RGCs after ONC. 

PMID- 24878626
TI  - Capsaicin induces apoptosis in human small cell lung cancer via the TRPV6
      receptor and the calpain pathway.
AB  - Capsaicin, the pungent ingredient of chili peppers, displays potent anti
      neoplastic activity in a wide array of human cancer cells. The present manuscript
      examines the signaling pathways underlying the apoptotic activity of capsaicin in
      human small cell lung cancer (SCLC) in vitro and in vivo. Studies in neuronal
      cells show that capsaicin exerts its biological activity via the transient
      receptor potential vanilloid (TRPV) superfamily of cation-channel receptors. The
      TRPV family is comprised of six members (TRPV1-6). Capsaicin is a known agonist
      of the TRPV1 receptor. We observed that capsaicin-induced apoptosis in human SCLC
      cells was mediated via the TRPV receptor family; however it was independent of
      TRPV1. Surprisingly, the apoptotic activity of capsaicin required the TRPV6
      receptor. Depletion of TRPV6 receptor by siRNA methodology abolished the
      apoptotic activity of capsaicin in SCLC cells. Immunostaining and ELISA showed
      that TRPV6 receptor was robustly expressed on human SCLC tissues (from patients)
      and SCLC cell lines but almost absent in normal lung tissues. This correlates
      with our results that capsaicin induced very little apoptosis in normal lung
      epithelial cells. The pro-apoptotic activity of capsaicin was mediated by the
      intracellular calcium and calpain pathway. The treatment of human SCLC cells with
      capsaicin increased the activity of calpain 1 and 2 by threefold relative to
      untreated SCLC cells. Such calpain activation, in response to capsaicin, was
      downstream of the TRPV6 receptor. Taken together, our data provide insights into
      the mechanism underlying the apoptotic activity of capsaicin in human SCLCs.

PMID- 24878629
TI  - The bone tissue of children and adolescents with Down syndrome is sensitive to
      mechanical stress in certain skeletal locations: a 1-year physical training
      program study.
AB  - The systemic complications of Down syndrome (DS) attenuate the osteogenic
      response to physical activity in DS patients. Through an interventional study we
      showed the effects of physical training on development of bone mineral content
      (BMC) and density (BMD) as well as on quantitative bone ultrasound (QUS)
      parameters in individuals with DS. A total of 42 children with DS were randomly
      assigned to either an exercising (DS-E, n=20, age 16 +/- 1.8 years) or non
      exercising group (DS-NE, n=22, age 16.9 +/- 1.5 years). DS-E group was assigned
      to a program of osteogenic activities with 60 min sessions twice a week, over 12
      month period. Bone mass measures were performed by dual X-ray absorpsiometry
      (DXA) at the spine and hip, and ultrasound attenuation (BUA) and velocity (SOS)
      assessed from the calcaneus by QUS device. All bone parameters had evolved with
      age, except for neck BMD. One year of training increased BMC values at lumbar
      spine (7%, p<.005) and total hip (10%, p<.05), and BMD values only at lumbar
      spine (4%, p<.05). Changes in BUA and SOS values were not evident following
      training. Trained individuals increased their motor skills measured through
      Eurofit tests. It was concluded that a program of osteogenic physical training
      may induce bone improvement in children with DS, but with a lower magnitude than
      that reported in the specialized literature for individuals without DS.

PMID- 24878631
TI  - A systematic review of the effects of motor interventions to improve motor,
      cognitive, and/or social functioning in people with severe or profound
      intellectual disabilities.
AB  - While it is generally agreed that motor activity promotes motor, cognitive, and
      social development, the specific benefits in people with severe or profound
      intellectual disabilities (S-PID) are as yet unknown. The aim of this study was
      to systematically review the evidence related to motor interventions designed to
      improve motor, cognitive, and/or social outcomes in people with S-PID. A
      systematic review of empirical studies published between 1982 and 2012 was
      conducted using four databases (MEDLINE, PsycINFO, ERIC, and CINAHL). Data were
      extracted regarding the aim of the study, study design, sample characteristics,
      theoretical framework, intervention, the measurement tools utilized, and
      outcomes. Of 295 articles reviewed, 46 met our inclusion criteria and covered 45
      different studies. Forty articles used single-subject designs and five used a
      group design. The majority of the articles focused on behavioural techniques with
      (n=21) or without (n=15) assistive technology. Theoretical frameworks were
      explicitly reported in nine (20%) of the 45 articles. Thirty-eight articles
      reported improvement in basic motor skills and eight articles reported
      improvement in recreational or more specialist motor skills. None of the articles
      reported negative effects due to motor interventions. Further research is
      required to determine which motor interventions are the most effective in
      improving motor outcomes and/or cognitive and social outcomes, and on the longer
      term effects of these interventions in people with S-PID. 

PMID- 24878630
TI  - The wellbeing of siblings of children with disabilities.
AB  - THE AIMS OF OUR STUDY WERE: (1) to estimate the extent of differences in
      wellbeing between siblings of children with disabilities or long-term health
      conditions and siblings of 'typically developing' children in a nationally
      representative cohort of Australian children (the Longitudinal Study of
      Australian Children); (2) to determine whether any between-group differences in
      wellbeing may be potentially attributable to between-group differences in
      exposure to socio-economic disadvantage. The results of our analyses were
      consistent with the existing literature in indicating that, in unadjusted
      comparisons, the siblings of children with long-term health conditions or
      disabilities: (1) had lower wellbeing than their peers on some, but not all,
      indicators of wellbeing; and (2) that where differences did exist the effect
      sizes were small. Our results add to the existing literature in: (1) indicating
      that adjusting for between-group differences in exposure to low SEP and
      associated adversities eliminated the statistical significance of unadjusted
      comparisons in the majority of instances; and (2) failing to find any evidence of
      deterioration over time in the wellbeing of siblings with long-term health
      conditions or disabilities over a two-year period from age 4/5 to age 6/7.

PMID- 24878632
TI  - Psychosocial Predictors of Mental Health Service Utilization Among Women During
      their Mid-Sixties.
AB  - This prospective study examined the longitudinal pathways to the utilization of
      mental health services among women in their mid-sixties. Earlier educational
      level, psychological symptoms, cigarette use, and physical diseases and later
      psychological symptoms were examined as predictors of mental health services
      utilization. The sample consisted of a prospective cohort of women (N = 511) who
      were followed from young adulthood (mean age = 32) to late midlife (mean age =
      65). Using structural equation modeling, the results supported a mediational
      model showing that earlier low educational level and greater psychological
      symptoms predicted increased cigarette smoking. Cigarette smoking predicted later
      physical diseases and symptoms. Physical diseases and symptoms were related to
      financial difficulty and later psychological symptoms and, ultimately, the use of
      mental health services by women in the mid-sixties.

PMID- 24878634
TI  - CBP-CITED4 is required for luteinizing hormone-triggered target gene expression
      during ovulation.
AB  - Pituitary-secreted luteinizing hormone (LH) induces ovulation by activating an
      extracellular regulated kinase 1/2 (ERK1/2) cascade. However, little is known
      regarding the ERK1/2 downstream effectors that are involved in regulating rapid,
      transient expression of LH-target gene in ovulatory follicles. By comparing the
      gene expression profiles of LH-stimulated wild type with ERK1/2-deleted ovarian
      granulosa cells (GCs), we identified Cited4 as a previously unknown LH target
      gene during ovulation. LH induced Cited4 expression in pre-ovulatory follicles in
      an ERK1/2-dependent manner. CITED4 formed an endogenous protein complex and
      docked on the promoters of LH and ERK1/2 target genes. Both CITED4 expression and
      CBP acetyltransferase activity leading to histone acetylation were indispensable
      for LH-induced ovulation-related events. LH induced dynamic histone acetylation
      changes in pre-ovulatory GCs, including the acetylation of histone H2B (Lys5) and
      H3 (Lys9). This was essential for the rapid responses and dramatic increases of
      LH target gene expressions by the ordered activation of ERK1/2 and CITED4-CBP. In
      addition, histone deacetylases (HDACs) antagonized CITED4-CBP to turn off
      expression of these genes after exposure to LH. Thus, we determined that CITED4
      was a novel LH and ERK1/2 target for triggering ovulation. These results support
      the proposition that LH induces rapid, significant gene expression in pre
      ovulatory follicles by modulating histone acetylation status. 

PMID- 24878636
TI  - Antiproliferative and quinone reductase-inducing activities of withanolides
      derivatives.
AB  - Two new and five known withanolides (jaborosalactones 2, 3, 4, 5, and 24) were
      isolated from the leaves of Jaborosa runcinata Lam. We also obtained some
      derivatives from jaborosalactone 5, which resulted to be the major isolated
      metabolite. The natural compounds as well as derivatives were evaluated for their
      antiproliferative activity and the induction of quinone reductase 1 (QR1; NQ01)
      activity. Structure-activity relationships revealed valuable information on the
      pharmacophore of withanolide-type compounds. Three compounds of this series
      showed significantly higher antiproliferative activity than jaborosalactone 5.
      The effect of these compounds on the cell cycle was determined. Furthermore, the
      ability of major compounds to induce QR1 was evaluated. It was found that all the
      active test compounds are monofunctional inducers that interact with Keap1. The
      most promising derivatives prepared from jaborosalactone 5 include (23R)
      4beta,12beta,21-trihydroxy-1,22-dioxo-12,23-cycloergostan-2,5,17,24-tetraen-26,23
      olide (18) and (23R)-21-acetoxy-12beta-hydroxy-1,22-dioxo-12,23-cycloergostan
      2,5,17,24-tetraen-26,23-lactame (20).

PMID- 24878635
TI  - Evidence of the innate antiviral and neuroprotective properties of progranulin.
AB  - BACKGROUND: Compelling data exist that show that normal levels of progranulin
      (PGRN) are required for successful CNS aging. PGRN production is also modulated
      by inflammation and infection, but no data are available on the production and
      role of PGRN during CNS HIV infection. METHODS: To determine the relationships
      between PGRN and HIV disease, neurocognition, and inflammation, we analyzed 107
      matched CSF and plasma samples from CHARTER, a well-characterized HIV cohort.
      Levels of PGRN were determined by ELISA and compared to levels of several
      inflammatory mediators (IFNgamma, IL-6, IL-10, IP-10, MCP-1, TNFalpha, IL-1beta,
      IL-4 and IL-13), as well as clinical, virologic and demographic parameters. The
      relationship between HIV infection and PGRN was also examined in HIV-infected
      primary human microglial cultures. RESULTS: In plasma, PGRN levels correlated
      with the viral load (VL, p<0.001). In the CSF of subjects with undetectable VL,
      lower PGRN was associated with neurocognitive impairment (p = 0.046). CSF PGRN
      correlated with CSF IP-10, TNFalpha and IL-10, and plasma PGRN correlated with
      plasma IP-10. In vitro, microglial HIV infection increased PGRN production and
      PGRN knockdown increased HIV replication, demonstrating that PGRN is an innate
      antiviral protein. CONCLUSIONS: We propose that PGRN plays dual roles in people
      living with HIV disease. With active HIV replication, PGRN is induced in infected
      macrophages and microglia and functions as an antiviral protein. In individuals
      without active viral replication, decreased PGRN production contributes to
      neurocognitive dysfunction, probably through a diminution of its neurotrophic
      functions. Our results have implications for the pathogenesis, biomarker studies
      and therapy for HIV diseases including HIV-associated neurocognitive dysfunction
      (HAND).

PMID- 24878637
TI  - Ruthenium(II) polypyridyl complexes: cellular uptake, cell image and apoptosis of
      HeLa cancer cells induced by double targets.
AB  - Studies have shown that ruthenium complexes have relatively strong anticancer
      activity, cell uptake of drugs have a crucial impact on the pharmacological
      activity, using autofluorescence of ruthenium complexes could effectively track
      cancer cells and drug distribution, transport accurately in real time. In this
      work, we present the synthesis and detailed characterization of two novel Ru(II)
      complexes with hydrophobic ancillary ligands, namely [Ru(bpy)2(5-idip)](2+) (RBD)
      and [Ru(phen)2(5-idip)](2+) (RPD) (5-idip = 2-indole-[4,5
      f][1,10]phenanthroline). We have shown that RPD can enter the HeLa cells
      efficiently through non-endocytotic, but energy-dependent mechanism and first
      accumulated in lysosomes, and then escape from the lysosomes and localize within
      the nuclei, efficiently lead to the inhibition of DNA transcription and
      translation and induced cell apoptosis. Further studies on the mechanism of
      apoptosis in HeLa cells demonstrate that RPD is able to induce mitochondria
      mediated apoptosis in HeLa cells through activation of initiator caspase-9 and
      down-stream effector caspase-3 and -7 and cleavage of PARP. We have also
      demonstrated that RPD bind to telomeric G-quadruplex DNA effectively and
      selectively, together with increased p21 and p16 expression. Our findings suggest
      that RPD induces HeLa cell apoptosis through mitochondria-mediated pathway and
      inhibition of telomerase activity. RPD may be a candidate for further evaluation
      as a chemotherapeutic agent for human cancers.

PMID- 24878638
TI  - Thiosemicarbazide, a fragment with promising indolamine-2,3-dioxygenase (IDO)
      inhibition properties.
AB  - With the aim to explore the interest of the thiosemicarbazide scaffold for the
      inhibition of the indoleamine 2,3-dioxygenase (IDO), a promising therapeutic
      target for anticancer immunotherapy, a series of 32 phenylthiosemicarbazide
      derivatives was prepared and their IDO inhibition evaluated. Our study
      demonstrated that among these derivatives, compound 14 characterized with a 4
      cyanophenyl group on the thiosemicarbazide was the more potent IDO inhibitor in
      this series being endowed with an IC50 of 1.2 MUM. The SAR depicted showed that
      substitution in the 3- and 4-position relative to the phenylthiosemicarbazide are
      very promising whereas substitution in the 2-position always leads to less potent
      or inactive derivatives. In fact the study highlighted a novel interesting
      scaffold for IDO inhibition for further development.

PMID- 24878640
TI  - Generation of an infectious Negev virus cDNA clone.
AB  - The genus Negevirus consists of insect-only viruses isolated from mosquitoes and
      sandflies. Here, we report the successful construction of a full-length
      infectious cDNA clone of Negev virus (NEGV) strain M30957. Viral RNA was
      transcribed in vitro and virus was readily rescued with or without the use of a
      cap analogue. These results strongly suggest that NEGV, and likely other members
      within the genus, is a non-segmented, single-stranded, positive-sense RNA virus. 

PMID- 24878641
TI  - RNA-binding region of Macrobrachium rosenbergii nodavirus capsid protein.
AB  - White tail disease (WTD) kills prawn larvae and causes drastic losses to the
      freshwater prawn (Macrobrachium rosenbergii) industry. The main causative agent
      of WTD is Macrobrachium rosenbergii nodavirus (MrNV). The N-terminal end of the
      MrNV capsid protein is very rich in positively charged amino acids and is
      postulated to interact with RNA molecules. N-terminal and internal deletion
      mutagenesis revealed that the RNA-binding region is located at positions 20-29,
      where 80 % of amino acids are positively charged. Substitution of all these
      positively charged residues with alanine abolished the RNA binding. Mutants
      without the RNA-binding region still assembled into virus-like particles,
      suggesting that this region is not a part of the capsid assembly domain. This
      paper is, to the best of our knowledge, the first to report the specific RNA
      binding region of MrNV capsid protein. 

PMID- 24878642
TI  - CKDu: A perfect storm.

PMID- 24878639
TI  - Highly pathogenic avian influenza A H5N1 and pandemic H1N1 virus infections have
      different phenotypes in Toll-like receptor 3 knockout mice.
AB  - Toll-like receptors (TLRs) play an important role in innate immunity to virus
      infections. We investigated the role of TLR3 in the pathogenesis of H5N1 and
      pandemic H1N1 (pH1N1) influenza virus infections in mice. Wild-type mice and
      those defective in TLR3 were infected with influenza A/HK/486/97 (H5N1) or
      A/HK/415742/09 (pH1N1) virus. For comparison, mice defective in the gene for
      myeloid differential factor 88 (MyD88) were also infected with the viruses,
      because MyD88 signals through a TLR pathway different from TLR3. Survival and
      body weight loss were monitored for 14 days, and lung pathology, the lung immune
      cell profile, viral load and cytokine responses were studied. H5N1-infected TLR3(
      /-) mice had better survival than H5N1-infected WT mice, evident by significantly
      faster regain of body weight, lower viral titre in the lung and fewer
      pathological changes in the lung. However, this improved survival was not seen
      upon pH1N1 infection of TLR3(-/-) mice. In contrast, MyD88(-/-) mice had an
      increased viral titre and decreased leukocyte infiltration in the lungs after
      infection with H5N1 virus and poorer survival after pH1N1 infection. In
      conclusion, TLR3 worsens the pathogenesis of H5N1 infection but not of pH1N1
      infection, highlighting the differences in the pathogenesis of these two viruses
      and the different roles of TLR3 in their pathogenesis.

PMID- 24878643
TI  - CKDu ravages the Salvadoran countryside.

PMID- 24878644
TI  - Chronic kidney disease of unknown etiology in agricultural communities.
AB  - In recent years, Central America, Egypt, India and Sri Lanka have reported a high
      prevalence of chronic kidney disease of unknown etiology in agricultural
      communities, predominantly among male farmworkers. This essay examines the
      disease's case definitions, epidemiology (disease burden, demographics,
      associated risk factors) and causal hypotheses, by reviewing published findings
      from El Salvador, Nicaragua, Costa Rica, Sri Lanka, Egypt and India. The range of
      confirmed chronic kidney disease prevalence was 17.9%-21.1%. Prevalence of
      reduced glomerular filtration (<60 mL/min/1.73 m2 body surface area) based on a
      single serum creatinine measurement was 0%-67% men and 0%-57% women. Prevalence
      was generally higher in male farmworkers aged 20-50 years, and varied by
      community economic activity and altitude. Cause was unknown in 57.4%-66.7% of
      patients. The dominant histopathological diagnosis was chronic tubulointerstitial
      nephritis. Associations were reported with agricultural work, agrochemical
      exposure, dehydration, hypertension, homemade alcohol use and family history of
      chronic kidney disease. There is no strong evidence for a single cause, and
      multiple environmental, occupational and social factors are probably involved.
      Further etiological research is needed, plus interventions to reduce preventable
      risk factors.

PMID- 24878645
TI  - Risk factors for reduced glomerular filtration rate in a Nicaraguan community
      affected by Mesoamerican nephropathy.
AB  - INTRODUCTION: Mesoamerican nephropathy, also known as chronic kidney disease of
      unknown etiology, is widespread in Pacific coastal Central America. The cause of
      the epidemic is unknown, but the disease may be linked to multiple factors,
      including diet as well as environmental and occupational exposures. As many as
      50% of men in some communities have Mesoamerican nephropathy. OBJECTIVE: Describe
      prevalence of reduced glomerular filtration rate in a region of Nicaragua
      suspected to harbor high rates of Mesoamerican nephropathy; and investigate
      potential risk factors for such reduction associated with agricultural work (such
      as pesticide exposure and specific agricultural tasks associated with increased
      heat stress); sugar consumption; and traditional factors such as age, sex,
      diabetes, hypertension and nephrotoxic medication use. METHODS: This study uses a
      cross-sectional design with nested case-control analysis. Cases were individuals
      with estimated glomerular filtration rates of <60mL/min/1.73m2 and controls were
      individuals with those >90mL/min/1.73m2, estimated using serum creatinine. Data
      on nutrition, past medical history, medication and substance use, and
      agricultural behaviors and exposures were collected using medical questionnaires
      from June through August, 2012. Venous blood and urine samples were collected to
      assess hemoglobin A1c, and dipstick proteinuria, respectively; anthropometry and
      blood pressure measurements were made using standard techniques. Analyses were
      conducted using chi square, and univariate and multiple logistic regression.
      RESULTS: Of 424 individuals in the study, 151 had an occupational history in
      agriculture. Prevalence of glomerular filtration rate <60mL/min/1.73m2 was 9.8%
      among women and 41.9% among men (male to female ratio = 4.3, p<0.0001).
      Proteinuria =300 mg/dL was observed in <10% of participants with decreased
      glomerular filtration rate. Hemoglobin A1c and use of NSAIDs were not associated
      with decreased glomerular filtration rate. Although systolic and diastolic blood
      pressure was higher among participants with decreased glomerular filtration rate
      (p <0.001), hypertension was uncommon. Significant agricultural risk factors for
      reduced glomerular filtration rate included increased lifetime days cutting
      sugarcane during the dry season (OR 5.86, 95% CI 2.45-14.01), nondeliberate
      pesticide inhalation (OR 3.31, 95% CI 1.32-8.31), and sugarcane chewing (OR 3.24,
      95% CI 1.39-7.58). CONCLUSIONS: Our findings demonstrate a high prevalence of
      chronic kidney disease not linked to traditional risk factors, and suggest it may
      be associated instead with occupational exposure to heat stress in conjunction
      with pesticide inhalation, sugarcane chewing and sugar intake during the workday.

PMID- 24878646
TI  - Epidemiology of chronic kidney disease in adults of Salvadoran agricultural
      communities.
AB  - INTRODUCTION: In El Salvador, chronic kidney disease is a serious and growing
      public health problem. Chronic renal failure was the first cause of hospital
      deaths in men and the fifth in women in 2011. OBJECTIVE: Determine prevalence of
      CKD, CKD risk factors (traditional and nontraditional) and renal damage markers
      in the adult population of specific rural areas in El Salvador; measure
      population distribution of renal function; and identify associated risk factors
      in CKD patients detected. METHODS: A cross-sectional analytical epidemiological
      study was conducted based on active screening for chronic kidney disease and risk
      factors in persons aged >=18 years during 2009-2011. Epidemiological and clinical
      data were gathered through personal history, as well as urinalysis for renal and
      vascular damage markers, determinations of serum creatinine and glucose, and
      estimation of glomerular filtration rates. Chronic kidney disease cases were
      confirmed at three months. Multiple logistical regression was used for
      statistical analysis. RESULTS: Prevalence of chronic kidney disease was 18%
      (23.9% for men and 13.9% for women) in 2388 persons: 976 men and 1412 women from
      1306 families studied. Chronic kidney disease with neither diabetes nor
      hypertension nor proteinuria >=1 g/L (51.9%) predominated. Prevalence of chronic
      renal failure was 11% (17.1% in men and 6.8% in women). Prevalence of renal
      damage markers was 12.5% (higher in men): microalbuminuria, 6.9%; proteinuria
      (0.3 g/L), 1.7%; proteinuria (1g/L), 0.6%; proteinuria (2 g/L), 0.4 %; and
      hematuria, 1.5%. Prevalence of chronic kidney disease risk factors was: diabetes
      mellitus, 9%; hypertension, 20.9%; family history of chronic kidney disease,
      16.5%; family history of diabetes mellitus, 18.5%; family history of
      hypertension, 30.6%; obesity, 21%; central obesity, 24.9%; NSAID use, 84.2%;
      smoking, 9.9%; alcohol use, 15%; agricultural occupation, 31.2%; and contact with
      agrochemicals, 46.7%. Chronic kidney disease was significantly associated with
      male sex, older age, hypertension, agricultural occupation, family history of
      chronic kidney disease and contact with the agrochemical methyl parathion.
      CONCLUSIONS: The results of this study support suggestions from other research
      that we are facing a new form of kidney disease that could be called agricultural
      nephropathy.

PMID- 24878647
TI  - Spatial distribution of unspecified chronic kidney disease in El Salvador by crop
      area cultivated and ambient temperature.
AB  - INTRODUCTION: Chronic kidney disease of unknown etiology is occurring in various
      geographic areas worldwide. Cases lack typical risk factors associated with
      chronic kidney disease, such as diabetes and hypertension. It is epidemic in El
      Salvador, Central America, where it is diagnosed with increasing frequency in
      young, otherwise-healthy male farmworkers. Suspected causes include agrochemical
      use (especially in sugarcane fields), physical heat stress, and heavy metal
      exposure. OBJECTIVE: To evaluate the geographic relationship between unspecified
      chronic kidney disease (unCKD) and nondiabetic chronic renal failure (ndESRD)
      hospital admissions in El Salvador with the proximity to cultivated crops and
      ambient temperatures. METHODS: Data on unCKD and ndESRD were compared with
      environmental variables, crop area cultivated (indicator of agrochemical use) and
      high ambient temperatures. Using geographically weighted regression analysis, two
      model sets were created using reported municipal hospital admission rates are per
      thousand population for unCKD 2006-2010 and rates of ndESRD 2005-2010
      [corrected]. These were assessed against local percent of land cultivated by crop
      (sugarcane, coffee, corn, cotton, sorghum, and beans) and mean maximum ambient
      temperature, with Moran's indices determining data clustering. Two-dimensional
      geographic models illustrated parameter spatial distribution. RESULTS: Bivariate
      geographically weighted regressions showed statistically significant correlations
      between percent area of sugarcane, corn, cotton, coffee, and bean cultivation, as
      well as mean maximum ambient temperature with both unCKD and ndESRD hospital
      admission rates. Percent area of sugarcane cultivation had greatest statistical
      weight (p <= 0.001; Rp2 = 0.77 for unCKD). The most statistically significant
      multivariate geographically weighted regression model for unCKD included percent
      area of sugarcane, cotton and corn cultivation (p <= 0.001; Rp2 = 0.80), while,
      for ndESRD, it included the percent area of sugarcane, corn, cotton and coffee
      cultivation (Rp2 = 0.52). Univariate unCKD and ndESRD Moran's I (0.20 and 0.33,
      respectively) indicated some degree of clustering. Ambient temperature did not
      improve multivariate geographically-weighted regression models for unCKD or
      ndESRD. Local bivariate Moran's indices with relatively high positive values and
      statistical significance (0.3-1.0, p <=0.05) indicated positive clustering
      between unCKD hospital admission rates and percent area of sugarcane as well as
      cotton cultivation. The greatest positive response for clustering values did not
      consistently plot near the highest temperatures; there were some positive
      clusters in regions of lower temperatures. Clusters of ndESRD were also observed,
      some in areas of relatively low chronic kidney disease incidence in western El
      Salvador. CONCLUSIONS: High temperatures do not appear to strongly influence
      occurrence of unCKDu proxies. CKDu in El Salvador may arise from proximity to
      agriculture to which agrochemicals are applied, especially in sugarcane
      cultivation. The findings of this preliminary ecological study suggest that more
      research is needed to assess and quantify presence of specific agrochemicals in
      high-CKDu areas.

PMID- 24878648
TI  - Clinical characteristics of chronic kidney disease of nontraditional causes in
      Salvadoran farming communities.
AB  - INTRODUCTION: Chronic kidney disease is a serious health problem in El Salvador.
      Since the 1990s, there has been an increase in cases unassociated with
      traditional risk factors. It is the second leading cause of death in men aged >18
      years. In 2009, it was the first cause of in-hospital death for men and the fifth
      for women. The disease has not been thoroughly studied. OBJECTIVE: Characterize
      clinical manifestations (including extrarenal) and pathophysiology of chronic
      kidney disease of nontraditional causes in Salvadoran farming communities.
      METHODS: A descriptive clinical study was carried out in 46 participants (36 men,
      10 women), identified through chronic kidney disease population screening of 5018
      persons. Inclusion criteria were age 18-59 years; chronic kidney disease at
      stages 2, 3a and 3b, or at 3a and 3b with diabetes or hypertension and without
      proteinuria; normal fundoscopic exam; no structural abnormalities on renal
      ultrasound; and HIV-negative. Examinations included social determinants;
      psychological assessment; clinical exam of organs and systems; hematological and
      biochemical parameters in blood and urine; urine sediment analysis; markers of
      renal damage; glomerular and tubular function; and liver, pancreas and lung
      functions. Renal, prostate and gynecological ultrasound; and Doppler
      echocardiography and peripheral vascular and renal Doppler ultrasound were
      performed. RESULTS: Patient distribution by chronic kidney disease stages: 2
      (32.6%), 3a (23.9%), 3b (43.5%). Poverty was the leading social determinant
      observed. Risk factor prevalence: agrochemical exposure (95.7%), agricultural
      work (78.3%), male sex (78.3%), profuse sweating during work (76.3%), malaria
      (43.5%), NSAID use (41.3%), hypertension (36.9%), diabetes (4.3%). General
      symptoms: arthralgia (54.3%), asthenia (52.2%), cramps (45.7%), fainting (30.4).
      Renal symptoms: nycturia (65.2%), dysuria (39.1%), foamy urine (63%). Markers of
      renal damage: macroalbuminuria (80.4%), beta2 microglobulin (78.2%), NGAL
      (26.1%). Renal function: hypermagnesuria (100%), hyperphosphaturia (50%),
      hypernatriuria (45.7%), hyperkaluria (23.9%), hypercalciuria (17.4%), electrolyte
      polyuria (43.5%), metabolic alkalosis (45.7%), hyponatremia (47.8%), hypocalcemia
      (39.1%), hypokalemia (30.4%), hypomagnesemia (19.6%). Imaging: Ultrasound showed
      fatty liver (93.5%) and vascular Doppler showed tibial artery damage (66.7%).
      Neurological symptoms: abnormal tendon reflexes (45.6%), Babinski sign and
      myoclonus (6.5%), sensorineural hearing loss (56.5%). CONCLUSIONS: This chronic
      kidney disease studied behaves clinically like chronic tubulointerstitial
      nephropathy, but with systemic manifestations not attributable to kidney disease.
      While male agricultural workers predominated, women and adolescents were also
      affected. Findings support a hypothesis of multifactorial etiology with a key
      role played by nephrotoxic environmental agents.

PMID- 24878649
TI  - Histopathology of chronic kidney disease of unknown etiology in Salvadoran
      agricultural communities.
AB  - INTRODUCTION: For at least a decade, a chronic kidney disease unassociated with
      diabetes mellitus, hypertension or any of the more common traditional causes, has
      been reported in Salvadoran agricultural communities. OBJECTIVE: Characterize
      histopathology of chronic kidney disease of unknown etiology in patients from
      Salvadoran agricultural communities, describe renal damage associated with each
      disease stage, and assess associations between histopathological alterations and
      sociodemographic variables. METHODS: The study involved 46 patients of both
      sexes, aged =18 years. After clinical, laboratory and imaging examinations,
      kidney biopsies were performed and renal tissue assessed for interstitial
      fibrosis, tubular atrophy, interstitial inflammatory infiltration, sclerosis,
      increase in glomerular size and extraglomerular vascular lesions (according to
      the Banff 97 classification used for kidney transplant rejection). Special
      staining was done: Schiff periodic acid, Masson trichrome and methenamine silver.
      Immunofluorescence techniques were used to evaluate IgA, IgG, IgM, complement C1q
      and C3, fibrin, and kappa and lambda light chain deposits. RESULTS: The main
      findings were interstitial fibrosis and tubular atrophy with or without
      inflammatory monocyte infiltration. In addition, generalized sclerosis, increased
      glomerular size, collapse of some glomerular tufts, and lesions of
      extraglomerular blood vessels (such as intimal proliferation and thickening and
      vacuolization of the tunica media) were observed. Interstitial fibrosis and
      glomerulosclerosis were associated with male sex. Sugarcane workers showed more
      interstitial fibrosis and tubular atrophy and less glomerulomegaly than other
      occupational groups. CONCLUSION: The morphological pattern in all biopsies was
      one of chronic tubulointerstitial nephropathy with secondary glomerular and
      vascular damage, in different stages of evolution of chronic kidney disease,
      independent of age, sex or occupation.

PMID- 24878650
TI  - Chronic kidney disease and associated risk factors in two Salvadoran farming
      communities, 2012.
AB  - INTRODUCTION: Chronic kidney disease is a global pandemic, affecting the majority
      of countries in the world. Its prevalence is approximately 10% and it is
      associated mainly with diabetes and high blood pressure. In El Salvador, it is
      the leading cause of hospital deaths among men. OBJECTIVE: Determine prevalence
      of chronic kidney disease and its risk factors in two Salvadoran farming
      communities. METHODS: From March through September 2012, a descriptive cross
      sectional study was conducted in two Salvadoran farming communities: Dimas
      Rodriguez (El Paisnal municipality) and El Jicaro (San Agustin municipality). The
      research involved both epidemiological and clinical methods. An active search for
      chronic kidney disease and its risk factors was carried out in the population
      aged >15 years. House-to-house visits were carried out to take family and
      individual health histories and gather data on social conditions and risk
      factors. A physical examination was performed, along with laboratory tests
      (urinalysis and blood chemistry) to measure renal function and detect markers for
      renal damage. RESULTS: A total of 223 persons of both sexes were studied. Overall
      prevalence of chronic kidney disease was 50.2%. Prevalence of chronic renal
      failure was 16.1%, with slight variations between the sexes. In El Jicaro, 77.3%
      of participants reported contact with agrochemicals and 76.6% were farmworkers;
      the respective figures for Dimas Rodriguez were 75.8% and 73.7%. The next most
      frequently reported risk factor was NSAID use, at 61.7% in El Jicaro and 77.9% in
      Dimas Rodriguez. CONCLUSIONS: CKD prevalence is alarming in these communities,
      among both young and old, men and women, independently of occupation. Health
      services must cope with the increased CKD burden observed, and are challenged to
      implement preventive strategies.

PMID- 24878651
TI  - Update on uncertain etiology of chronic kidney disease in Sri Lanka's north
      central dry zone.
AB  - INTRODUCTION: This manuscript updates a review previously published in a local
      journal in 2012, about a new form of chronic kidney disease that has emerged over
      the past two decades in the north-central dry zone of Sri Lanka, where the
      underlying causes remain undetermined. Disease burden is higher in this area,
      particularly North Central Province, and affects a rural and disadvantaged
      population involved in rice-paddy farming. Over the last decade several studies
      have been carried out to estimate prevalence and identify determinants of this
      chronic kidney disease of uncertain etiology. OBJECTIVE: Summarize the available
      evidence on prevalence, clinical profile and risk factors of chronic kidney
      disease of uncertain etiology in the north-central region of Sri Lanka. METHODS:
      PubMed search located 16 manuscripts published in peer-reviewed journals. Three
      peer-reviewed abstracts of presentations at national scientific conferences were
      also included in the review. RESULTS: Disease prevalence was 5.1%-16.9% with more
      severe disease seen in men than in women. Patients with mild to moderate stages
      of disease were asymptomatic or had nonspecific symptoms; urinary sediments were
      bland; 24-hour urine protein excretion was <1 g; and ultrasound demonstrated
      bilateral small kidneys. Interstitial fibrosis was the main pathological feature
      on renal biopsy. The possibility of environmental toxins affecting vulnerable
      population groups in a specific geographic area was considered in evaluating
      etiological factors. Pesticide residues were detected in affected patients'
      urine, and mycotoxins detected in foods were below maximum statutory limits.
      Calcium-bicarbonate-type water with high levels of fluoride was predominant in
      endemic regions. Significantly high levels of cadmium in urine of cases compared
      to controls, as well as the disease's dose-related response to these levels, has
      drawn attention to this element as a possible contributing factor. Familial
      clustering of patients is suggestive of a polygenic inheritance pattern
      comparable to that associated with diseases of multifactorial etiology.
      CONCLUSIONS: Available data suggest that chronic kidney disease of uncertain
      etiology is an environmentally acquired disease, but to date no definitive causal
      factor has been identified. Geographic distribution and research findings suggest
      a multifactorial etiology.

PMID- 24878652
TI  - Chronic kidney disease in Central American agricultural communities: challenges
      for epidemiology and public health.
AB  - This paper contextualizes the chronic kidney disease epidemic and related burden
      of disease affecting Central American farming communities. It summarizes the two
      main causal hypotheses (heat stress and agrochemicals), draws attention to the
      consequences of dichotomous reasoning concerning causality, and warns of
      potential conflicts of interest and their role in "manufacturing doubt." It
      describes some methodological errors that compromise past study findings and
      cautions against delaying public health actions until a conclusive understanding
      is reached about the epidemic's causes and underlying mechanisms. It makes the
      case for a comprehensive approach to the historical, social and epidemiological
      facts of the epidemic, for critically assessing existing studies and for enhanced
      rigor in new research.

PMID- 24878653
TI  - Chronic kidney disease of unknown etiology should be renamed chronic agrochemical
      nephropathy.
AB  - Epidemics of chronic kidney disease not attributable to common causes have
      recently been observed in Central America and Asia. Since the etiology is
      unclear, the disease is often known by terms such as chronic kidney disease of
      unknown etiology. There is growing evidence that risk factors include rural
      agricultural work and agrochemical exposure. The disease should be renamed
      chronic agrochemical nephropathy to highlight the most likely etiology and draw
      attention to the condition.

PMID- 24878654
TI  - International Society of Nephrology's perspective on the emergence of chronic
      kidney diseases of unknown/undetermined etiology.

PMID- 24878655
TI  - Chronic kidney disease in our farming communities: implications of an epidemic.

PMID- 24878656
TI  - Chronic kidney disease of unknown etiology: a disease related to global warming?

PMID- 24878658
TI  - Poverty: The common denominator of CKD's global threat.

PMID- 24878657
TI  - CKDu: Strategies for saving lives now.

PMID- 24878659
TI  - Catherine A. Poole (1933-2014).

PMID- 24878660
TI  - Early onset degenerative dementias: demographic characteristics and etiologic
      classification in a tertiary referral center.
AB  - Early onset dementia (EOD) is a major diagnostic challenge as it often presents
      with atypical features and may be attributed to treatable diseases. Primary
      degenerative dementias (Alzheimer's disease-AD, frontotemporal lobar degeneration
      FTLD, Lewy body dementia-LBD), although traditionally considered to affect older
      people, are still a main cause of EOD. 491 demented patients were assessed from
      January 1, 2003 to December 31, 2010 in the Neurology Department of a tertiary
      referral center. Patients were classified as AD, behavioral variant
      frontotemporal dementia (bvFTD), non-fluent agrammatic variant primary
      progressive aphasia (naPPA), semantic variant PPA (svPPA), corticobasal
      degeneration (CBD), or progressive supranuclear palsy (PSP) who also met criteria
      for naPPA and LBD. Finally, their demographic characteristics were analysed,
      according to age at onset (EOD <65 years, late onset dementia-LOD >=65 years).
      From the 491 patients, 137 (27.9 %) were EOD. In the EOD group, 52 (38 %) were
      diagnosed with bvFTD, 34 (24.8 %) with AD, 27 (19.7 %) with naPPA, 10 (7.2 %)
      with svPPA, 12 (8.8 %) with CBD or PSP, and 2 (1.5 %) with LBD. Demographic
      characteristics did not differ significantly among diagnostic categories in the
      EOD group, while in the LOD group FTLD patients were younger and more frequently
      men compared to both AD and LBD patients. EOD patients had more years of
      education than LOD patients. Degenerative disorders as causes of EOD are not
      rare. High clinical alertness is warranted to achieve correct and timely
      diagnosis.

PMID- 24878661
TI  - ADC evaluation of the corticospinal tract in multiple sclerosis.
AB  - Apparent diffusion coefficient (ADC) values derived from diffusion-weighted MR
      imaging (DWI) provide important information about tissues. The goal of this study
      was to evaluate the ADC values in the corticospinal tract regions in multiple
      sclerosis (MS). The ADC values of 42 patients with multiple sclerosis and 46
      healthy people were measured. The ADC values in the corticospinal tract at the
      capsula interna posterior crus from six points and mesencephalon from three
      points bilaterally in MS patients were compared with those of controls. An ANOVA
      post hoc test was used to analyse the differences in mean ADC values between the
      MS and control groups. The mean ADC values of the right (p = 0.008) and left
      internal capsules (p = 0.000) and right (p = 0.002) and left mesencephalons (p =
      0.044) in MS patients were significantly lower than in the control group. There
      was no significant difference between the right and left side ADC values in MS (p
      = 0.313 vs. p = 0.223) and control groups (p = 0.756 vs. p = 0.105),
      respectively. The mean ADC values of the corticospinal tract in MS patients were
      significantly lower than in the control group. This decreased diffusion may be
      the result of cellular infiltration due to inflammation, cytotoxic oedema,
      demyelination or remyelination processes.

PMID- 24878663
TI  - Structural investigation of the interaction between the tandem SH3 domains of c
      Cbl-associated protein and vinculin.
AB  - c-Cbl-associated protein (CAP) is an important cytoskeletal adaptor protein
      involved in the regulation of adhesion turnover. The interaction between CAP and
      vinculin is critical for the recruitment of CAP to focal adhesions. The tandem
      SH3 domains (herein termed SH3a and SH3b) of CAP are responsible for its
      interaction with vinculin. However, the structural mechanism underlying the
      interaction between CAP and vinculin is poorly understood. In this manuscript, we
      report the solution structure of the tandem SH3 domains of CAP. Our NMR and ITC
      data indicate that the SH3a and SH3b domains of CAP simultaneously bind to a long
      proline-rich region of vinculin with different binding specificities.
      Furthermore, the crystal structures of the individual SH3a and SH3b domains
      complexed with their substrate peptides indicate that Q807(SH3a) and D881(SH3b)
      are the critical residues determining the different binding specificities of the
      SH3 domains. Based on the obtained structural information, a model of the SH3ab
      vinculin complex was generated using MD simulation and SAXS data. 

PMID- 24878662
TI  - Inherent dynamics of head domain correlates with ATP-recognition of P2X4
      receptors: insights gained from molecular simulations.
AB  - P2X receptors are ATP-gated ion channels involved in many physiological
      functions, and determination of ATP-recognition (AR) of P2X receptors will
      promote the development of new therapeutic agents for pain, inflammation, bladder
      dysfunction and osteoporosis. Recent crystal structures of the zebrafish P2X4
      (zfP2X4) receptor reveal a large ATP-binding pocket (ABP) located at the subunit
      interface of zfP2X4 receptors, which is occupied by a conspicuous cluster of
      basic residues to recognize triphosphate moiety of ATP. Using the engineered
      affinity labeling and molecular modeling, at least three sites (S1, S2 and S3)
      within ABP have been identified that are able to recognize the adenine ring of
      ATP, implying the existence of at least three distinct AR modes in ABP. The open
      crystal structure of zfP2X4 confirms one of three AR modes (named AR1), in which
      the adenine ring of ATP is buried into site S1 while the triphosphate moiety
      interacts with clustered basic residues. Why architecture of ABP favors AR1 not
      the other two AR modes still remains unexplored. Here, we examine the potential
      role of inherent dynamics of head domain, a domain involved in ABP formation, in
      AR determinant of P2X4 receptors. In silico docking and binding free energy
      calculation revealed comparable characters of three distinct AR modes. Inherent
      dynamics of head domain, especially the downward motion favors the preference of
      ABP for AR1 rather than AR2 and AR3. Along with the downward motion of head
      domain, the closing movement of loop139-146 and loop169-183, and structural
      rearrangements of K70, K72, R298 and R143 enabled ABP to discriminate AR1 from
      other AR modes. Our observations suggest the essential role of head domain
      dynamics in determining AR of P2X4 receptors, allowing evaluation of new
      strategies aimed at developing specific blockers/allosteric modulators by
      preventing the dynamics of head domain associated with both AR and channel
      activation of P2X4 receptors. 

PMID- 24878666
TI  - Structure-direction in the crystallization of ITW zeolites using 2-ethyl-1,3,4
      trimethylimidazolium.
AB  - 2-Ethyl-1,3,4-trimethylimidazolium is so far the fifth and largest imidazolium
      cation able to produce the pure silica zeolite ITW. The crystallization is not
      direct, but occurs as an in situ transformation from either the chiral HPM-1
      (STW) zeolite or the new layered zeolite precursor HPM-2 (preMTF) and results in
      large interpenetrated crystals with a habit so far unseen in this zeolite. The
      results of chemical, physicochemical and structural characterization allow us to
      discuss structure-direction issues. The large cation is occluded intact in the
      zeolite, causing an expansion of the zeolite volume. The degree of polarization
      of the Si-O bond is similar to that observed in other as-made ITW zeolites. 

PMID- 24878664
TI  - Development and characterization of a preclinical model of breast cancer lung
      micrometastatic to macrometastatic progression.
AB  - Most cancer patients die with metastatic disease, thus, good models that
      recapitulate the natural process of metastasis including a dormancy period with
      micrometastatic cells would be beneficial in developing treatment strategies.
      Herein we report a model of natural metastasis that balances time to complete
      experiments with a reasonable dormancy period, which can be used to better study
      metastatic progression. The basis for the model is a 4T1 triple negative
      syngeneic breast cancer model without resection of the primary tumor. A cell
      titration from 500 to 15,000 GFP tagged 4T1 cells implanted into fat pad number
      four of immune proficient eight week female BALB/cJ mice optimized speed of the
      model while possessing metastatic processes including dormancy and beginning of
      reactivation. The frequency of primary tumors was less than 50% in animals
      implanted with 500-1500 cells. Although implantation with over 10,000 cells
      resulted in 100% primary tumor development, the tumors and macrometastases formed
      were highly aggressive, lacked dormancy, and offered no opportunity for
      treatment. Implantation of 7,500 cells resulted in >90% tumor take by 10 days; in
      30-60 micrometastases in the lung (with many animals also having 2-30 brain
      micrometastases) two weeks post-implantation, with the first small
      macrometastases present at five weeks; many animals displaying macrometastases at
      five weeks and animals becoming moribund by six weeks post-implantation. Using
      the optimum of 7,500 cells the efficacy of a chemotherapeutic agent for breast
      cancer, doxorubicin, given at its maximal tolerated dose (MTD; 1 mg/kg weekly)
      was tested for an effect on metastasis. Doxorubicin treatment significantly
      reduced primary tumor growth and lung micrometastases but the number of
      macrometastases at experiment end was not significantly affected. This model
      should prove useful for development of drugs to target metastasis and to study
      the biology of metastasis. 

PMID- 24878665
TI  - Altered synaptic plasticity in Tourette's syndrome and its relationship to motor
      skill learning.
AB  - Gilles de la Tourette syndrome is a neuropsychiatric disorder characterized by
      motor and phonic tics that can be considered motor responses to preceding inner
      urges. It has been shown that Tourette patients have inferior performance in some
      motor learning tasks and reduced synaptic plasticity induced by transcranial
      magnetic stimulation. However, it has not been investigated whether altered
      synaptic plasticity is directly linked to impaired motor skill acquisition in
      Tourette patients. In this study, cortical plasticity was assessed by measuring
      motor-evoked potentials before and after paired associative stimulation in 14
      Tourette patients (13 male; age 18-39) and 15 healthy controls (12 male; age 18
      33). Tic and urge severity were assessed using the Yale Global Tic Severity Scale
      and the Premonitory Urges for Tics Scale. Motor learning was assessed 45 minutes
      after inducing synaptic plasticity and 9 months later, using the rotary pursuit
      task. On average, long-term potentiation-like effects in response to the paired
      associative stimulation were present in healthy controls but not in patients. In
      Tourette patients, long-term potentiation-like effects were associated with more
      and long-term depression-like effects with less severe urges and tics. While
      motor learning did not differ between patients and healthy controls 45 minutes
      after inducing synaptic plasticity, the learning curve of the healthy controls
      started at a significantly higher level than the Tourette patients' 9 months
      later. Induced synaptic plasticity correlated positively with motor skills in
      healthy controls 9 months later. The present study confirms previously found long
      term improvement in motor performance after paired associative stimulation in
      healthy controls but not in Tourette patients. Tourette patients did not show
      long-term potentiation in response to PAS and also showed reduced levels of motor
      skill consolidation after 9 months compared to healthy controls. Moreover,
      synaptic plasticity appears to be related to symptom severity. 

PMID- 24878667
TI  - Histological difference between pulsed wave laser and continuous wave laser in
      endovenous laser ablation.
AB  - BACKGROUND: Endovenous laser ablation to saphenous veins has been popular as a
      minimally invasive treatment for chronic venous insufficiency. However, adverse
      effects after endovenous laser ablation using continuous wave laser still remain.
      Pulsed wave with enough short pulse duration and sufficiently long thermal
      relaxation time may avoid the excess energy delivery, which leads to the
      perforation of the vein wall. METHOD: (1) Free radiation: Laser is radiated in
      blood for 10 s. (2) Endovenous laser ablation: Veins were filled with blood and
      placed in saline. Endovenous laser ablations were performed. RESULTS: (1) There
      were clots on the fiber tips with continuous wave laser while no clots with
      pulsed wave laser. (2) In 980-nm continuous wave, four of 15 specimens had ulcers
      and 11 of 15 had perforation. In 1470-nm continuous wave with 120 J/cm of linear
      endovenous energy density, two of three presented ulcers and one of three showed
      perforation. In 1470-nm continuous wave with 60 J/cm of linear endovenous energy
      density, two of four had ulcers and two of four had perforation. In 1320-nm
      pulsed wave, there were neither ulcers nor perforation in the specimens.
      CONCLUSIONS: While endovenous laser ablation using continuous wave results in
      perforation in many cases, pulsed wave does not lead to perforation.

PMID- 24878668
TI  - Effect of different solutions on color stability of acrylic resin-based dentures.
AB  - The aim of this study was to evaluate the effect of thermocycling and immersion
      in mouthwash or beverage solutions on the color stability of four different
      acrylic resin-based dentures (Onda Cryl, OC; QC20, QC; Classico, CL; and
      Lucitone, LU). The factors evaluated were type of acrylic resin, immersion time,
      and solution (mouthwash or beverage). A total of 224 denture samples were
      fabricated. For each type of resin, eight samples were immersed in mouthwashes
      (Plax-Colgate, PC; Listerine, LI; and Oral-B, OB), beverages (coffee, CP; cola,
      C; and wine, W), and artificial saliva (AS; control). The color change (DE) was
      evaluated before (baseline) and after thermocycling (T1), and after immersion in
      solution for 1 h (T2), 3 h (T3), 24 h (T4), 48 h (T5), and 96 h (T6). The CIE Lab
      system was used to determine the color changes. The thermocycling test was
      performed for 5000 cycles. Data were submitted to three-way repeated-measures
      analysis of variance and Tukey's test (p<0.05). When the samples were immersed in
      each mouthwash, all assessed factors, associated or not, significantly influenced
      the color change values, except there was no association between the mouthwash
      and acrylic resin. Similarly, when the samples were immersed in each beverage,
      all studied factors influenced the color change values. In general, regardless of
      the solution, LU exhibited the greatest DE values in the period from T1 to T5;
      and QC presented the greatest DE values at T6. Thus, thermocycling and immersion
      in the various solutions influenced the color stability of acrylic resins and QC
      showed the greatest color alteration.

PMID- 24878670
TI  - Periodontal conditions of Colombian university students aged 16 to 35.
AB  - Epidemiological data on the periodontal health and oral hygiene practices of
      young individuals in Latin America are limited. This study was conducted in a
      sample of 355 first-year students randomly selected from 3,251 new students
      entering the largest university in Colombia. Participants received a periodontal
      examination and were interviewed about oral hygiene practices. Specifically, this
      study assessed the relationship between oral hygiene practices (including smoking
      tobacco) and plaque accumulation and/or periodontal bleeding on probing (BOP).
      Participants had extensive plaque accumulation and BOP, with a mean O'Leary
      plaque index of 56% and mean BOP of 37%. Both measures were higher for proximal
      surfaces. Plaque indices of at least 50% were not associated with any oral
      hygiene factors; however, plaque index and use of dental floss were associated
      with a BOP of at least 50%. Frequency of tooth brushing was higher in female than
      in male participants. Only 5% of participants reported smoking tobacco. On
      average, participants had 2.7+/-4.6 pockets of at least 4 mm (18% of participants
      had >=5 and 9% of participants had >=10 pockets of this depth, respectively). On
      average, participants had 2.1+/-4.4 sites with clinical attachment loss of at
      least 2 mm (15% and 6% of participants had >=5 and >=10 sites with this level of
      loss). Only 8% of participants were diagnosed with moderate periodontitis, and no
      participants were diagnosed with severe periodontitis. In conclusion, although
      participants had high levels of plaque and BOP, signs of advanced destructive
      periodontal disease were minimal.

PMID- 24878671
TI  - Evaluation of dentists' knowledge of the use of oral exfoliative cytology in
      clinical practice.
AB  - Oral exfoliative cytology (EC) is a rapid and practical complementary test that
      can be used in the diagnosis of various diseases. The objectives of this study
      were to assess dentists' knowledge of EC and to disseminate information on the
      technique. The study included 240 dentists from the city of Anapolis (Goias,
      Brazil) who answered a questionnaire regarding demographic data and data relating
      to EC and who then received information on the technique. The data revealed that
      26.92% of the dentists did not know about EC. Among those who reported knowledge
      of EC, 33.91% did not know the procedures for performing the technique, and
      85.38% had no experience with EC. In addition, 54.09% of the answers regarding
      the instrument used to collect the material and 56.82% of the answers concerning
      suitable fixatives were inappropriate. Although 73.02% of the dentists adequately
      identified the pathologies for which EC is recommended, it was concluded that the
      respondents had poor knowledge of EC. There is a need to increase dentists'
      awareness of this subject and of EC's use in diagnostic practices. 

PMID- 24878672
TI  - Comparison of different retreatment techniques and root canal sealers: a scanning
      electron microscopic study.
AB  - The aim of this study was to evaluate the effectiveness of two retreatment
      techniques, in terms of the operating time and scanning electron microscopy (SEM)
      results, in removing three different root canal sealers from root canals that
      were previously filled with gutta-percha. Sixty extracted single-rooted human
      premolars were divided into three groups and filled with iRoot SP, MM Seal, and
      AH Plus sealers, along with gutta-percha, through a lateral compaction technique.
      Root canal fillings of the samples were removed by ESI ultrasonic tips or R-Endo
      files. The time to reach the working length was recorded. Longitudinally
      sectioned samples were examined under SEM magnification. Each picture was
      evaluated in terms of the residual debris. Data were statistically analyzed with
      the Kruskall-Wallis test. No statistically significant differences were found in
      terms of operating time (p>0.05). Significant differences in the number of debris
      free dentinal tubules were found among the root canal thirds, but this finding
      was not influenced by the experimental group (p<0.05). Resin sealer tags were
      observed inside the dentinal tubules in the MM Seal group. Under the conditions
      of this study, it may be established that there was no difference among the
      sealers and retreatment techniques.

PMID- 24878673
TI  - Photoelastic stress analysis in mandibular bone surrounding bar-clip overdenture
      implants.
AB  - The aim of this in vitro study was to evaluate, using the photoelastic analysis
      method, the stress distribution in mandibular bone surrounding a bar-clip
      overdenture when 2 implant angulations were simulated. Two mandibular
      photoelastic models were manufactured, with 2 implants embedded in the
      interforaminal region: model 1-PAPI, a photoelastic analysis model with parallel
      implants; and model 2-PAAI, a photoelastic analysis model with angled implants. A
      bar-clip retention system and an overdenture were positioned over the implants,
      and loads of 1.0, 2.0 and 3.0 bars were applied. The resultant stresses that
      developed in the supporting structure were photoelastically monitored and were
      recorded photographically. The results showed that there were no similarities in
      the areas of stress among the photoelastic resin models when the angulation of
      the implants was evaluated. Model 1-PAPI presented a higher stress concentration
      at the implant apex, while in model 2-PAAI, there were higher stress
      concentrations on the mesial and distal implant faces. Within the limitations of
      this study, it was concluded that the PAPI photoelastic model demonstrated better
      stress transfer compared to the PAAI model, since the forces oriented along the
      axis were better absorbed by the bone.

PMID- 24878674
TI  - Factors associated with dental fluorosis in school children in southern Brazil: a
      cross-sectional study.
AB  - This cross-sectional study assessed risk factors for dental fluorosis (DF) among
      8- to 12-year-old children in southern Brazil. Children attending 20 schools were
      randomly selected (n=1,196). They were interviewed and their parents answered a
      questionnaire that was sent home. Prevalence of DF was 8.53% (modified Dean's
      criteria), and the prevalence of severe DF was 0.17%. The results of multiple
      logistic regression analyses indicated that DF was associated with a higher
      frequency of tooth brushing and with initial use of fluoride toothpaste at the
      emergence of the first tooth. DF does not constitute a public health problem in
      southern Brazil.

PMID- 24878675
TI  - Self-efficacy and chronic pain outcomes: a meta-analytic review.
AB  - A meta-analysis was performed to evaluate overall strengths of relation between
      self-efficacy (SE) and functioning (pain severity, functional impairment,
      affective distress) in chronic pain samples, as well as potential moderating
      effects of sociodemographic characteristics and methodologic factors on these
      associations. In sum, 86 samples (N = 15,616) fulfilled selection criteria for
      analysis. SE had negative overall correlations with impairment, affective
      distress, and pain severity although considerable heterogeneity was observed for
      all effect sizes. Age, pain duration, SE scale content (SE for functioning
      despite pain vs SE for pain control vs SE for managing other symptoms such as
      emotional distress) and type of impairment measure (self-report vs task
      performance) had significant moderating effects on SE-impairment associations. SE
      affective distress relations were moderated by employment status and SE scale
      content. Finally, moderator analyses of studies having longitudinal designs
      indicated associations between baseline SE, and each outcome at follow-up
      remained significant in prospective studies that had statistically controlled for
      effects of baseline responses on that outcome. Hence, SE is a robust correlate of
      key outcomes related to chronic pain and a potentially important risk/protective
      factor that has implications for subsequent functioning in affected groups.
      PERSPECTIVE: Meta-analysis indicated that SE has significant overall associations
      with impairment, affective distress, and pain severity within chronic pain
      samples and identified several factors that contribute to variability in effect
      sizes. Findings highlighted SE as a robust correlate and potentially important
      risk/protective factor for subsequent adjustment in affected groups.

PMID- 24878676
TI  - Paternal influences on treatment outcome of behavioral parent training in
      children with attention-deficit/hyperactivity disorder.
AB  - This study aims to explore the influence of paternal variables on outcome of
      behavioral parent training (BPT) in children with attention-deficit/hyperactivity
      disorder (ADHD). 83 referred, school-aged children with ADHD were randomly
      assigned to BPT plus ongoing routine clinical care (RCC) or RCC alone. Treatment
      outcome was based on parent-reported ADHD symptoms and behavioral problems.
      Moderator variables included paternal ADHD symptoms, depressive symptoms, and
      parenting self-efficacy. We conducted repeated measures analyses of variance
      (ANOVA) for all variables, and then analyzed the direction of interaction effects
      by repeated measures ANOVA in high and low scoring subgroups. Paternal ADHD
      symptoms and parenting self-efficacy played a moderating role in decreasing
      behavioral problems, but not in decreasing ADHD symptoms. Paternal depressive
      symptoms did not moderate either treatment outcome. BPT is most beneficial in
      reducing children's behavioral problems when their fathers have high levels of
      ADHD symptoms or high-parenting self-efficacy. 

PMID- 24878678
TI  - Genetics in endocrinology: genetic variation in deiodinases: a systematic review
      of potential clinical effects in humans.
AB  - Iodothyronine deiodinases represent a family of selenoproteins involved in
      peripheral and local homeostasis of thyroid hormone action. Deiodinases are
      expressed in multiple organs and thyroid hormone affects numerous biological
      systems, thus genetic variation in deiodinases may affect multiple clinical
      endpoints. Interest in clinical effects of genetic variation in deiodinases has
      clearly increased. We aimed to provide an overview for the role of deiodinase
      polymorphisms in human physiology and morbidity. In this systematic review,
      studies evaluating the relationship between deiodinase polymorphisms and clinical
      parameters in humans were eligible. No restrictions on publication date were
      imposed. The following databases were searched up to August 2013: Pubmed, EMBASE
      (OVID-version), Web of Science, COCHRANE Library, CINAHL (EbscoHOST-version),
      Academic Search Premier (EbscoHOST-version), and ScienceDirect. Deiodinase
      physiology at molecular and tissue level is described, and finally the role of
      these polymorphisms in pathophysiological conditions is reviewed. Deiodinase type
      1 (D1) polymorphisms particularly show moderate-to-strong relationships with
      thyroid hormone parameters, IGF1 production, and risk for depression. D2 variants
      correlate with thyroid hormone levels, insulin resistance, bipolar mood disorder,
      psychological well-being, mental retardation, hypertension, and risk for
      osteoarthritis. D3 polymorphisms showed no relationship with inter-individual
      variation in serum thyroid hormone parameters. One D3 polymorphism was associated
      with risk for osteoarthritis. Genetic deiodinase profiles only explain a small
      proportion of inter-individual variations in serum thyroid hormone levels.
      Evidence suggests a role of genetic deiodinase variants in certain
      pathophysiological conditions. The value for determination of deiodinase
      polymorphism in clinical practice needs further investigation. 

PMID- 24878677
TI  - Justice and rejection sensitivity in children and adolescents with ADHD symptoms.
AB  - Justice sensitivity captures individual differences in the frequency with which
      injustice is perceived and the intensity of emotional, cognitive, and behavioral
      reactions to it. Persons with ADHD have been reported to show high justice
      sensitivity, and a recent study provided evidence for this notion in an adult
      sample. In 1,235 German 10-to 19-year olds, we measured ADHD symptoms, justice
      sensitivity from the victim, observer, and perpetrator perspective, the frequency
      of perceptions of injustice, anxious and angry rejection sensitivity, depressive
      symptoms, conduct problems, and self-esteem. Participants with ADHD symptoms
      reported significantly higher victim justice sensitivity, more perceptions of
      injustice, and higher anxious and angry rejection sensitivity, but significantly
      lower perpetrator justice sensitivity than controls. In latent path analyses,
      justice sensitivity as well as rejection sensitivity partially mediated the link
      between ADHD symptoms and comorbid problems when considered simultaneously. Thus,
      both justice sensitivity and rejection sensitivity may contribute to explaining
      the emergence and maintenance of problems typically associated with ADHD
      symptoms, and should therefore be considered in ADHD therapy. 

PMID- 24878679
TI  - Genome-wide screening of copy number variants in children born small for
      gestational age reveals several candidate genes involved in growth pathways.
AB  - BACKGROUND: The etiology of prenatal-onset short stature with postnatal
      persistence is heterogeneous. Submicroscopic chromosomal imbalances, known as
      copy number variants (CNVs), may play a role in growth disorders. OBJECTIVE: To
      analyze the CNVs present in a group of patients born small for gestational age
      (SGA) without a known cause. PATIENTS AND METHODS: A total of 51 patients with
      prenatal and postnatal growth retardation associated with dysmorphic features
      and/or developmental delay, but without criteria for the diagnosis of known
      syndromes, were selected. Array-based comparative genomic hybridization was
      performed using DNA obtained from all patients. The pathogenicity of CNVs was
      assessed by considering the following criteria: inheritance; gene content;
      overlap with genomic coordinates for a known genomic imbalance syndrome; and
      overlap with CNVs previously identified in other patients with prenatal-onset
      short stature. RESULTS: In 17 of the 51 patients, 18 CNVs were identified. None
      of these imbalances has been reported in healthy individuals. Nine CNVs, found in
      eight patients (16%), were categorized as pathogenic or probably pathogenic.
      Deletions found in three patients overlapped with known microdeletion syndromes
      (4q, 10q26, and 22q11.2). These imbalances are de novo, gene rich and affect
      several candidate genes or genomic regions that may be involved in the mechanisms
      of growth regulation. CONCLUSION: Pathogenic CNVs in the selected patients born
      SGA were common (at least 16%), showing that rare CNVs are probably among the
      genetic causes of short stature in SGA patients and revealing genomic regions
      possibly implicated in this condition.

PMID- 24878680
TI  - Could different treatment approaches in acromegaly influence life expectancy? A
      comparative study between Bulgaria and Campania (Italy).
AB  - BACKGROUND: Mortality in acromegaly strictly depends on optimal control of GH and
      IGF1 levels. Modern medical therapy with somatostatin analogs (SSAs) and GH
      receptor antagonists (GHRAs) is not available in many countries due to funding
      restrictions. This retrospective, comparative, cohort study investigated the
      impact of different treatment modalities on disease control (GH and IGF1) and
      mortality in acromegaly patients. METHODS: Two cohorts of patients with
      acromegaly from Bulgaria (n=407) and Campania, Italy (n=220), were compared, and
      mortality rates were evaluated during a 10-year period (1999-2008). RESULTS: The
      major difference in treatment approach between cohorts was the higher utilization
      of SSAs and GHRAs in Italy, leading to a decreased requirement for radiotherapy.
      Significantly more Italian than Bulgarian patients had achieved disease control
      (50.1 vs 39.1%, P=0.005) at the last follow-up. Compared with the general
      population, the Bulgarian cohort had a decreased life expectancy with a
      standardized mortality ratio (SMR) of 2.0 (95% CI 1.54-2.47) that was restored to
      normal in patients with disease control - SMR 1.25 (95% CI 0.68-1.81). Irradiated
      patients had a higher cerebrovascular mortality - SMR 7.15 (95% CI 2.92-11.37).
      Internal analysis revealed an independent role of age at diagnosis and last GH
      value on all-cause mortality and radiotherapy on cerebrovascular mortality.
      Normal survival rates were observed in the Italian cohort: SMR 0.66 (95% CI 0.27
      1.36). CONCLUSIONS: Suboptimal biochemical control was associated with a higher
      mortality in the Bulgarian cohort. Modern treatment options that induce a strict
      biochemical control and reduce the necessity of radiotherapy might influence the
      life expectancy. Other factors, possibly management of comorbidities, could
      contribute to survival rates.

PMID- 24878681
TI  - A combination of mild hypothermia and sevoflurane affords long-term protection in
      a modified neonatal mouse model of cerebral hypoxia-ischemia.
AB  - BACKGROUND: Infant brain injury from hypoxia-ischemia (HI) can lead to life-long
      impairment, but protective strategies are lacking. Short-term but not long-term
      protection has been demonstrated in the Rice-Vannucci neonatal brain ischemia
      model (RVM) by volatile anesthetic administration before HI, while exposure
      during HI has not been tested. In the current study, we evaluated a combination
      of sevoflurane and mild hypothermia as a protective approach during HI, both
      short- and long-term, by introducing intubation and mechanical ventilation to the
      RVM. METHODS: The right common carotid artery was ligated in 10-day-old mice
      during brief sevoflurane anesthesia, followed by a 2-hour recovery with the dam.
      Littermates were then randomized to either: HI spontaneously breathing 10% oxygen
      for 60 minutes (the classical RVM); HI-Protect mild hypothermia and orotracheal
      intubation and mechanical ventilation with 3.5% sevoflurane in 10% oxygen for 60
      minutes; or Room Air spontaneously breathing room air for 60 minutes. In a
      nonsurviving cohort, cerebral oxygenation was monitored in the area at risk and
      the contralateral hemisphere during HI or HI-Protect using visible-light
      spectroscopy (Spectros Corp). Mean arterial blood pressure and heart rate were
      measured. Arterial blood gases were obtained. Right/left brain hemispheric weight
      ratios and brain damage scores were determined 1 week after HI. In another group,
      learning and behavior were assessed in young adulthood (9 weeks) using
      spontaneous locomotion, Morris water maze, and apomorphine injection. RESULTS:
      During HI, ipsilateral and contralateral brain oxygenation, arterial blood
      pressures, blood gases, and glucose levels were similar in both ischemic groups,
      while heart rate was slower in the HI-Protect group. One week after ischemia,
      brain hemispheric weight ratios and injury scores in several brain regions were
      significantly worse after HI, compared with HI-Protect. Nine weeks after HI,
      Morris water maze hidden platform and reversal platform escape latencies,
      measures of spatial memory function, were superior after HI-Protect, compared
      with HI (P < 0.0001). HI-Protect animals demonstrated significantly less circling
      behavior after an apomorphine challenge (P < 0.0001), a measure of striatal
      integrity. CONCLUSIONS: To test the neuroprotective effects of volatile
      anesthetics during neonatal brain ischemia, we developed a modification of the
      RVM. By using mechanical ventilation and endotracheal intubation, sevoflurane
      administration during HI was survivable. The combination of sevoflurane
      administration and mild hypothermia during HI conferred not only short-term
      structural, but also long-term functional protection, compared with littermates
      treated according to the RVM. These findings warrant further studies to improve
      neurological outcome in critically ill infants.

PMID- 24878683
TI  - The implementation of quantitative electromyographic neuromuscular monitoring in
      an academic anesthesia department.
AB  - BACKGROUND: Although experts agree on the importance of quantitative
      neuromuscular blockade monitoring, particularly for managing reversal, such
      monitoring is not in widespread use. We describe the processes and results of our
      departmental experience with the introduction of such quantitative monitoring.
      METHODS: In mid-2010, the senior authors became concerned about the management of
      nondepolarizing neuromuscular blockers (NMB) by providers within the department,
      based on personal observations and on a review of a departmental quality
      assurance/adverse event database. This review indicated the occurrence of 2 to 4
      reintubations/year in the postanesthesia care unit (PACU) that were deemed to be
      probably or possibly related to inadequate reversal. In response, quantitative
      blockade equipment (Datex-Omeda ElectroSensorTM EMG system) was installed in all
      our main operating rooms in January 2011. This introduction was accompanied by an
      extensive educational effort. Adoption of the system was slow; by mid-2011, the
      quantitative system was being used in <50% of cases involving nondepolarizing
      relaxants and adverse NMB-related events continued to occur. Therefore, starting
      in August 2011 and extending over the next 2 years, we performed a series of 5
      separate sampling surveys in the PACU in which train-of-four (TOF) ratios were
      recorded in 409 tracheally extubated adult patients who had received
      nondepolarizing NMB (almost exclusively rocuronium) as well as in 73 patients who
      had not received any nondepolarizing NMB. After each survey, the results were
      presented to the entire department, along with discussions of individual cases,
      reviews of the recent literature regarding quantitative monitoring and further
      education regarding the use of the quantitative system. RESULTS: In the initial
      (August 2011) PACU survey of 96 patients receiving nondepolarizing NMBs, 31% had
      a TOF ratio of <=0.9, 17% had a ratio of <=0.8, and 4 patients (4%) had ratios of
      <=0.5. A record review showed that the quantitative monitoring system had been
      used to monitor reversal in only 51% of these patients, and 23% of patients had
      no evidence of any monitoring, including qualitative TOF assessment. By December
      of 2012 (after 2 interim PACU monitoring surveys), a fourth survey showed 15% of
      101 monitored patients had a TOF ratio <=0.9, and only 5% had ratios <=0.8. (P <
      0.05 vs August 2011). Clear documentation of reversal using the quantitative
      system was present in 83% of cases (P < 0.05 vs August 2011). A final survey in
      July 2013 showed nearly identical values to those from December 2012. The lowest
      TOF ratio observed in any patient not receiving a nondepolarizing NMB was 0.92.
      There were no changes in the patterns of either rocuronium or neostigmine use
      over the duration of the project (through December 2012), and there have been no
      cases of NMB-related reintubations in the PACU during the last 2 years.
      DISCUSSION: Implementation of universal electromyographic-based quantitative
      neuromuscular blockade monitoring required a sustained process of education along
      with repeated PACU surveys and feedback to providers. Nevertheless, this effort
      resulted in a significant reduction in the incidence of incompletely reversed
      patients in the PACU.

PMID- 24878682
TI  - Inflammatory pain may induce cognitive impairment through an interlukin-6
      dependent and postsynaptic density-95-associated mechanism.
AB  - BACKGROUND: Pain might be associated with cognitive impairment in humans.
      However, the characterization of such effects in a preclinical model and the
      investigation of the underlying mechanisms remain largely to be determined. We
      therefore sought to establish a system to determine the effect of pain on
      cognitive function in mice. METHODS: Complete Freund's adjuvant (CFA) was
      injected in the hindpaw of 5- to 8-month-old wild-type and interleukin-6 knockout
      mice. Learning and memory function, and the levels of interleukin-6 and
      postsynaptic density (PSD)-95 in the cortex and hippocampus of mice were
      assessed. RESULTS: We found that the CFA injection-induced pain in the mice at 3
      and 7 days after injection and decreased the freezing time (30.1 [16.5] vs 56.8
      [28.1] seconds, P =0.023) in the tone test, which assesses the hippocampus
      independent learning and memory function, but not in a context test of Fear
      Conditioning System (15.8 [6.7] vs 18.6 [8.8] seconds, P =0.622), which assesses
      the hippocampus-dependent learning and memory function, at 3 days after
      injection. Consistently, the CFA injection increased interleukin-6 (248% [11.6]
      vs 100% [7.9], P < 0.0001) and decreased the PSD-95 (40% [10.0] vs 100% [20.3], P
      < 0.0001) level in the cortex, but not hippocampus (95% [8.6] vs 100% [9.3], P
      =0.634), in the mice. The CFA injection induced neither reduction in the cortex
      PSD-95 levels nor cognitive impairment in the interleukin-6 knockout mice.
      CONCLUSIONS: These results suggest that pain induced by CFA injection might
      increase interleukin-6 levels and decrease PSD-95 levels in the cortex, but not
      hippocampus of mice, leading to hippocampus-independent cognitive impairment in
      mice. These findings call for further investigation to determine the role of pain
      in cognitive function.

PMID- 24878684
TI  - C-reactive protein kinetics after major surgery.
AB  - BACKGROUND: Diagnosis of sepsis in the postoperative period is a challenge.
      Measurements of inflammatory markers, such as C-reactive protein (CRP), have been
      proposed in medical patients, but the interpretation of these values in surgical
      patients is more difficult. We evaluated the changes in blood CRP levels and
      white blood cell count in postoperative patients with and without infection.
      METHODS: All patients admitted to our 34-bed Department of Intensive Care after
      major (elective or emergency) cardiac, neuro-, vascular, thoracic, or abdominal
      surgery during a 4-month period were prospectively included. Patients were
      screened daily and characterized as infected or noninfected. CRP levels and white
      blood cell counts were recorded daily in all patients for up to 7 days after the
      surgical intervention. RESULTS: Of the 151 patients enrolled, 115 underwent
      elective surgery and 36 emergency surgery; cardiac surgery was performed in 49
      patients, neurosurgery in 65, abdominal surgery in 25, vascular surgery in 7, and
      thoracic surgery in 5. In noninfected patients (n = 117), mean CRP values
      increased from baseline to postoperative day (POD) 3 (P < 0.0001, estimated mean
      difference [EMD] = 99.7 mg/L [95% confidence interval, 85.6-113.8]) and then
      decreased until POD 7 but remained higher than the level at baseline (P < 0.0001,
      EMD = 49.2 mg/L [95% confidence interval, 27.1-71.2]). Postoperative infection
      occurred in 20 patients (13.2%). In these patients, CRP values were already
      higher on POD 1 than in noninfected patients (P = 0.0054). CONCLUSIONS: CRP
      levels increase in the first week after major surgery but to a much larger extent
      in infected than in noninfected patients. Persistently high CRP levels after POD
      4, especially when >100 mg/L, suggest the presence of a postoperative infection.

PMID- 24878685
TI  - Broad-spectrum antiviral property of polyoxometalate localized on a cell surface.
AB  - Cs2K4Na[SiW9Nb3O40] has broad antiviral ability including anti-Influenza A, 
      Influenza B, -HSV-1, -HSV-2, -HIV-1, and -HBV. A series of antivirus and/or
      biochemical experiments and X-ray nanotomography analysis confirm that this kind
      of broad-spectrum antiviral property is mainly due to its localization on the
      cell surface. 

PMID- 24878687
TI  - Exploring the Providers Perspective of Health and Social Service Availability for
      Immigrants and Refugees in a Southern Urban Community.
AB  - As the foreign-born population continues to grow and increasingly expand into
      inland U.S. cities, they experience insufficient resources and facilities to
      support their unique health and social needs. The purpose of this study was to
      describe provider perspectives on health and social services for immigrants and
      refugees in a southern metropolitan city with a rapidly increasing foreign-born
      population. Ten health and social service providers participated in an
      ethnographic study using surveys, in-depth interviews, participant observation,
      and document review methods. Providers identified the greatest need for
      immigrants and refugees was access to urgent health services and management of
      chronic illnesses. Barriers and facilitators to service were related to
      accessibility, availability, affordability, and acceptability factors. Findings
      indicate that despite the establishment of population specific service
      organizations, immigrants and refugees continue to experience unmet health and
      social needs associated with sociocultural, economic, and political contextual
      factors. 

PMID- 24878686
TI  - A Culturally Adapted Smoking Cessation Intervention for Korean Americans: A
      Mediating Effect of Perceived Family Norm Toward Quitting.
AB  - Korean men and women have the highest current smoking rates across all Asian
      ethnic subgroups in the United States. This is a 2-arm randomized controlled
      study of a culturally adapted smoking cessation intervention. The experimental
      condition received eight weekly 40-min individualized counseling sessions that
      incorporated Korean-specific cultural elements, whereas the control condition
      received eight weekly 10-min individualized counseling sessions that were not
      culturally adapted. All participants also received nicotine patches for 8 weeks.
      One-hundred nine Korean immigrants (91 men and 18 women) participated in the
      study. The rate of biochemically verified 12-month prolonged abstinence was
      significantly higher for the experimental condition than the control condition
      (38.2 vs. 11.1 %, chi (2) = 10.7, p < 0.01). Perceived family norm significantly
      mediated the effect of cessation intervention on abstinence. Smoking cessation
      intervention for Korean Americans should be culturally adapted and involve family
      members to produce a long-term treatment effect. 

PMID- 24878688
TI  - Effect of exercise intensity on post-exercise oxygen consumption and heart rate
      recovery.
AB  - PURPOSE: There is some evidence that measures of acute post-exercise recovery are
      sensitive to the homeostatic stress of the preceding exercise and these
      measurements warrant further investigation as possible markers of training load.
      The current study investigated which of four different measures of metabolic and
      autonomic recovery was most sensitive to changes in exercise intensity. METHODS:
      Thirty-eight moderately trained runners completed 20-min bouts of treadmill
      exercise at 60, 70 and 80% of maximal oxygen uptake (VO2max) and four different
      recovery measurements were determined: the magnitude of excess post-exercise
      oxygen consumption (EPOCMAG), the time constant of the oxygen consumption
      recovery curve (EPOCtau), heart rate recovery within 1 min (HRR60s) and the time
      constant of the heart rate recovery curve (HRRtau) . RESULTS: Despite significant
      differences in exercise parameters at each exercise intensity, only EPOCMAG
      showed significantly slower recovery with each increase in exercise intensity at
      the group level and in the majority of individuals. EPOCtau was significantly
      slower at 70 and 80% of VO2max vs. 60% VO2max and HRRtau was only significantly
      slower when comparing the 80 vs. 60% VO2max exercise bouts. In contrast, HRR60s
      reflected faster recovery at 70 and 80% of VO2max than at 60% VO2max. CONCLUSION:
      Of the four recovery measurements investigated, EPOCMAG was the most sensitive to
      changes in exercise intensity and shows potential to reflect changes in the
      homeostatic stress of exercise at the group and individual level. Determining
      EPOCMAG may help to interpret the homeostatic stress of laboratory-based research
      trials or training sessions.

PMID- 24878689
TI  - Dimensions of pure chronic fatigue: psychophysical, cognitive and biological
      correlates in the chronic fatigue syndrome.
AB  - OBJECTIVES: To investigate associated dimensions of fatigue regarding cognitive
      impairment, psychomotor performances, muscular effort power and circulating
      cytokine levels and their relations to symptom intensity in a sample of pure
      chronic fatigue syndrome (CFS) patients without overlapping objective sleepiness
      or sleep disorders. METHODS: 16 CFS patients were compared to 14 matched
      controls. We assessed structured symptom-scales, polysomnography, multiple sleep
      latency tests, attention (Zazzo-Cancellation ZCT, digit-symbol-substitution
      DSST), psychomotor vigilance and speed (PVT, finger tapping test, FTT),
      dynamometer handgrip force (tonic and phasic trials) and circulating cytokines
      (IFN-gamma, IL-1b, IL-6, IL-8, IL-10, TNF-alpha). RESULTS: In addition to
      fatigue, CFS patients presented with higher affective symptom intensity and worse
      perceived sleep quality. Polysomnography showed more slow-wave sleep and
      microarousals in CFS but similar sleep time, efficiency and light-sleep durations
      than controls. Patients presented with impaired attention (DSST, ZCT), slower
      reaction times (PVT) but not with lower hit rates (FTT). Notwithstanding lower
      grip strength during tonic and phasic trials, CFS also presented with higher
      fatigability during phasic trials. Cytokine levels were increased for IL-1b, IL
      8, IL-10 and TNF-alpha and fatigue intensity was correlated to grip strength and
      IL-8. CONCLUSIONS: In contrast to sleepiness, chronic fatigue is a more complex
      phenomenon that cannot be reduced to one single measured dimension (i.e., sleep
      propensity). Showing its relations to different measurements, our study reflects
      this multidimensionality, in a psychosomatic disorder such as CFS. To obtain
      objective information, routine assessments of fatigue should rule out sleepiness,
      combine aspects of mental and physical fatigue and focus on fatigability.

PMID- 24878690
TI  - Inspiratory muscle warm-up does not improve cycling time-trial performance.
AB  - PURPOSE: This study examined the effects of an active cycling warm-up, with and
      without the addition of an inspiratory muscle warm-up (IMW), on 10-km cycling
      time-trial performance. METHODS: Ten cyclists (VO2 = 65 +/- 9 mL kg(-1) min(-1))
      performed a habituation 10-km cycling time-trial and three further time-trials
      preceded by either no warm-up (CONT), a cycling-specific warm-up (CYC) comprising
      three consecutive 5-min bouts at powers corresponding to 70, 80, and 90% of the
      gas exchange threshold, or a cycling-specific warm-up preceded by an IMW (CYC +
      IMW) comprising two sets of 30 inspiratory efforts against a pressure-threshold
      load of 40% maximal inspiratory pressure (MIP). The cycling warm-up was followed
      by 2-min rest before the start of the time-trial. RESULTS: Time-trial performance
      times during CYC (14.75 +/- 0.79 min) and CYC + IMW (14.70 +/- 0.75 min) were not
      different, although both were faster than CONT (14.99 +/- 0.90 min) (P < 0.05).
      Throughout the time-trial, physiological (minute ventilation, breathing pattern,
      pulmonary gas exchange, heart rate, blood lactate concentration and pH) and
      perceptual (limb discomfort and dyspnoea) responses were not different between
      CYC and CYC + IMW. Baseline MIP during CONT and CYC was 151 +/- 31 and 156 +/- 39
      cmH2O, respectively, and was unchanged following the time-trial. MIP increased by
      8% after IMW (152 +/- 27 vs. 164 +/- 27 cmH2O, P < 0.05) and returned to baseline
      after the time-trial. CONCLUSIONS: Improvements in 10-km cycling time-trial
      performance following an active cycling warm-up were not magnified by the
      addition of an IMW. Therefore, an appropriately designed active whole-body warm
      up does adequately prepare the inspiratory muscles for cycling time-trials
      lasting approximately 15 min.

PMID- 24878691
TI  - HIT maintains performance during the transition period and improves next season
      performance in well-trained cyclists.
AB  - PURPOSE: To investigate the effects of combining low-intensity endurance training
      (LIT) with one high-intensity endurance training (HIT) session every 7-10 days
      (EXP, n = 7) vs. traditional approach focusing on LIT (TRAD, n = 6) during the
      transition period. The effects of different training strategies during the
      transition period were investigated after the transition period and at the
      beginning of the subsequent competition season. METHODS: Well-trained cyclists
      were tested after the competition season, after an 8-week transition period, and
      after a 16-week preparatory period, before the subsequent competition season. The
      only difference between groups was a larger time with HIT during the transition
      phase in EXP. RESULTS: It was very likely that EXP had a larger impact on power
      output at 4 mmol L(-1) [la(-)] after both the transition period and after the
      preparatory period than TRAD [between-group change (90% CI): 10.6% (8.2%) and
      12.9% (11.9%), respectively]. It was very likely that EXP had a larger impact on
      mean power output in the 40-min all-out trial after the transition period than
      TRAD [between-group change 12.4% (7.6%)]. EXP was also likely to have a larger
      improvement in the 40-min trial performance from pre-test to after the
      preparatory period than TRAD [between-group change 6.0% (6.6%)]. CONCLUSION: The
      present findings suggest that HIT sessions should be incorporated during the
      transition phase to avoid reduction in fitness and performance level and thereby
      increase the likelihood of improved performance from the end of one season to the
      beginning of the subsequent season.

PMID- 24878693
TI  - Modelling road accident blackspots data with the discrete generalized Pareto
      distribution.
AB  - This study shows how road traffic networks events, in particular road accidents
      on blackspots, can be modelled with simple probabilistic distributions. We
      considered the number of crashes and the number of fatalities on Spanish
      blackspots in the period 2003-2007, from Spanish General Directorate of Traffic
      (DGT). We modelled those datasets, respectively, with the discrete generalized
      Pareto distribution (a discrete parametric model with three parameters) and with
      the discrete Lomax distribution (a discrete parametric model with two parameters,
      and particular case of the previous model). For that, we analyzed the basic
      properties of both parametric models: cumulative distribution, survival,
      probability mass, quantile and hazard functions, genesis and rth-order moments;
      applied two estimation methods of their parameters: the MU and (MU+1) frequency
      method and the maximum likelihood method; used two goodness-of-fit tests: Chi
      square test and discrete Kolmogorov-Smirnov test based on bootstrap resampling;
      and compared them with the classical negative binomial distribution in terms of
      absolute probabilities and in models including covariates. We found that those
      probabilistic models can be useful to describe the road accident blackspots
      datasets analyzed. 

PMID- 24878692
TI  - Sensation seeking and drunk driving: the mediational role of social norms and
      self-efficacy.
AB  - The aim of this work was to examine the role of sensation seeking in drunk
      driving by youths, and the potential mediational effect of social, cognitive and
      emotional variables on their relationship. To this end, a survey was conducted on
      274 drivers (164 females and 110 males) aged 24.36+/-2.96 years (range 18-30
      years). The results obtained confirm the significance of sensation seeking to
      drunk driving by youths and the mediating role of biased self-efficacy
      perceptions in their relationship. The important practical implications of this
      finding on the development of effective interventions to prevent the risks of
      drunk driving in youths are discussed. 

PMID- 24878694
TI  - Child care, socio-economic status and problem behavior: a study of gene
      environment interaction in young Dutch twins.
AB  - The influences of formal child care before age 4 on behavioral problems at 3, 5,
      and 7 years of age were assessed in 18,932 Dutch twins (3,878 attended formal
      child care). The effect of formal child care was studied on the average level of
      problem behavior and as moderator of genetic and non-genetic influences, while
      taking into account effects of sex and parental socio-economic status (SES).
      There was a small association between attending formal child care and higher
      externalizing problems, especially when SES was low. Heritability was lower for
      formal child care and in lower SES conditions. These effects were largest at age
      7 and for externalizing problems. In 7 year-old boys and girls, the difference in
      heritability between the formal child care group of low SES and the home care
      group of high SES was 30% for externalizing and ~20% for internalizing problems.
      The decrease in heritability was explained by a larger influence of the
      environment, rather than by a decrease in genetic variance. These results support
      a bioecological model in which heritability is lower in circumstances associated
      with more problem behavior.

PMID- 24878695
TI  - Antipredator behavior QTL: differences in rainbow trout clonal lines derived from
      wild and hatchery populations.
AB  - Variation in antipredator behavior may partially explain the survival differences
      seen between wild and hatchery trout and salmon. Antipredator behavior is thought
      to change during the domestication process, along with other traits.
      Investigations of antipredator behavior could benefit conservation efforts and
      supplementation programs. Our goal was to characterize the antipredator behavior
      in clonal rainbow trout lines derived from either wild or hatchery populations
      and identify genetic loci associated with variation between lines. We identified
      several behaviors that varied between clonal lines and QTL for several behavioral
      and size traits. Characterizing genetic variation underlying these behaviors may
      prove valuable in future conservation efforts by enabling monitoring of allele
      frequencies of loci affecting predation in wild populations. 

PMID- 24878696
TI  - PAH exposure biomarkers are associated with clinico-chemical changes in the brick
      kiln workers in Pakistan.
AB  - In this study we investigated the clinico-chemical parameters and the level of
      exposure of brick kiln workers to polycyclic aromatic hydrocarbons (PAHs) in
      Punjab (Pakistan). The brick kiln workers and a non-occupationally exposed group
      were recruited for comparative analysis of urinary biomarkers of PAH exposure
      (i.e. 1-hydroxypyrene (1-OHPyr), alpha-naphthol and beta-naphthol) and blood
      level of superoxide dismutase (SOD), as a biomarker of oxidative stress and other
      hematologic parameters. Questionnaires were used to document information on socio
      demographic characteristics of all the subjects. The analysis of urinary
      biomarkers showed higher median concentrations of 1-OHPyr, and alpha- and beta
      naphthols in brick kiln workers (1.53, 3.65 and 1.53 MUmol/mol-Cr, respectively)
      than non-occupationally exposed group (0.62, 0.64 and 0.66 MUmol/mol-Cr,
      respectively). The 1-OHPyr in brick kiln workers was above the occupational
      exposure level. Among the clinical parameters of brick kiln workers, hemoglobin
      (Hb) and red blood cells (RBCs) were very low and closely associate with 1-OHPyr
      and beta-naphthol. Additionally, the white blood cells (WBCs) and superoxide
      dismutase (SOD) were also elevated in brick kiln workers, which suggested
      inflammatory symptoms and high oxidative stress. The results show that regardless
      of possibly being affected by the poor nutrition, the anemic state and
      hematological changes observed in brick kiln workers may be associated with their
      exposure to smoke present in the environment of brick kilns.

PMID- 24878697
TI  - Overexpression of transient receptor potential vanilloid 2 is associated with
      poor prognosis in patients with esophageal squamous cell carcinoma.
AB  - Transient receptor potential vanilloid 2 (TRPV2) was proved to play a crucial
      role in the tumor progression of various cancers. The association between the
      expression of TRPV2 and clinical outcome in cancer patients has not been studied
      yet. We aim to elucidate the role of TRPV2 in predicting prognosis of patients
      with esophageal squamous cell carcinoma (ESCC). Fresh frozen samples were
      collected immediately from 170 patients with ESCC after surgical resection from
      2003 to 2008, including 45 pairs of tumor tissues and non-tumor tissues. TRPV2
      expression was measured by quantitative real-time PCR. TRPV2 mRNA was over
      expressed in ESCC tissues and cell lines. High expression of TRPV2 was observed
      more frequently in patients with advanced pT stage (P < 0.001), lymph node
      metastasis (P = 0.010) and advanced pathological stage (P = 0.001). Patients with
      high expression of TRPV2 (>44.40, n = 83) had worse 5-year disease-specific
      survival (40.0 vs 62.6 %, P < 0.001) and disease-free survival (38.4 vs 61.5 %, P
      < 0.001) than that with low expression (<= 44.40, n = 87). Multivariate analysis
      found that the expression of TRPV2 mRNA (HR 2.19, 95 % CI 1.39-3.46, P = 0.031)
      and pN category (HR 2.13, 95 % CI 1.36-3.33, P = 0.001) were independent
      prognostic factors. Overexpression of TRPV2 mRNA was associated with poor
      prognosis and might serve as a novel prognostic biomarker for resected ESCC
      patients in early stage.

PMID- 24878698
TI  - Overexpression of Dickkopf-1 predicts poor prognosis for patients with
      hepatocellular carcinoma after orthotopic liver transplantation by promoting
      cancer metastasis and recurrence.
AB  - Our previous data had shown that Dickkopf-1 (DKK1) combined with beta-catenin was
      a novel prognostic predictor for hepatocellular carcinoma (HCC) patients.
      However, the role and mechanism of DKK1 in HCC recurrence or metastasis remain
      poorly understand. This study was to assess the role of DKK1 in tumor metastasis
      for patients with hepatocellular carcinoma after orthotopic liver transplantation
      (OLT). The expression of DKK1 protein was detected in hepatic cell lines, HCC
      cell lines, and HCC patients after OLT with different potential of metastasis.
      After DKK1 expression in the HCCLM3 cells was downregulated by siRNA-mediated
      approach, the role of DKK1 in cell invasion and metastasis was investigated. cDNA
      genechip was used to analyze the differential expressed genes related with DKK1
      in two pairs of HCC cells. The prognostic significance of DKK1 was further
      assessed by Kaplan-Meier and Cox regression analyses in 148 HCC patients after
      OLT. The expression of DKK1 protein was higher in the high-invasive HCC cells and
      HCC patients of the disease recurrence group. With the downregulation of DKK1,
      HCCLM3 cells showed decreased aggressiveness in vitro and lower metastatic
      ability in vivo. DKK1 could regulate many genes involved in biological processes
      and pathways related with tumor progression. Furthermore, DKK1 overexpression
      correlated with tumor microvessel density in clinical HCC samples. Multivariate
      analysis revealed that DKK1 was an independent prognostic indicator for overall
      survival and cumulative recurrence in this cohort of HCC patients post-OLT.
      Collectively, overexpression of DKK1 was implicated in invasion/metastasis of HCC
      after OLT and DKK1 overexpression may be potential molecular therapeutic targets
      for liver cancer. 

PMID- 24878699
TI  - Transit dosimetry in dynamic IMRT with an a-Si EPID.
AB  - Using an amorphous silicon (a-Si) EPID for transit dosimetry requires detailed
      characterization of its dosimetric response in a variety of conditions. In this
      study, a measurement-based model was developed to calibrate an a-Si EPID response
      to dose for transit dosimetry by comparison with a reference ionization chamber.
      The ionization chamber reference depth and the required additional buildup
      thickness for electronic portal imaging devices (EPID) transit dosimetry were
      determined. The combined effects of changes in radiation field size, phantom
      thickness, and the off-axis distance on EPID transit dosimetry were
      characterized. The effect of scattered radiation on out-of-field response was
      investigated for different field sizes and phantom thicknesses by evaluation of
      the differences in image profiles and in-water measured profiles. An algorithm
      was developed to automatically apply these corrections to EPID images based on
      the user-specified field size and phantom thickness. The average phantom
      thickness and an effective field size were used for IMRT fields, and images were
      acquired in cine mode in the presence of an anthropomorphic phantom. The
      effective field size was defined as the percentage of the jaw-defined field that
      was involved during the delivery. Nine head and neck dynamic IMRT fields were
      tested by comparison with a MatriXX two-dimensional array dosimeter using the
      Gamma (3%, 3 mm) evaluation. A depth of 1.5 cm was selected as the ionization
      chamber reference depth. An additional 2.2 mm of copper buildup was added to the
      EPID. Comparison of EPID and MatriXX dose images for the tested fields showed
      that using a 10% threshold, the average number of points with Gamma index <1 was
      96.5%. The agreement in the out-of field area was shown by selection of a 2%
      threshold which on average resulted in 94.8% of points with a Gamma index <1. The
      suggested method is less complicated than previously reported techniques and can
      be used for all a-Si EPIDs regardless of the manufacturer.

PMID- 24878702
TI  - Defining oral health: a prerequisite for any health policy.

PMID- 24878701
TI  - Next-generation sequencing of RNA and DNA isolated from paired fresh-frozen and
      formalin-fixed paraffin-embedded samples of human cancer and normal tissue.
AB  - Formalin-fixed, paraffin-embedded (FFPE) tissues are an invaluable resource for
      clinical research. However, nucleic acids extracted from FFPE tissues are
      fragmented and chemically modified making them challenging to use in molecular
      studies. We analysed 23 fresh-frozen (FF), 35 FFPE and 38 paired FF/FFPE
      specimens, representing six different human tissue types (bladder, prostate and
      colon carcinoma; liver and colon normal tissue; reactive tonsil) in order to
      examine the potential use of FFPE samples in next-generation sequencing (NGS)
      based retrospective and prospective clinical studies. Two methods for DNA and
      three methods for RNA extraction from FFPE tissues were compared and were found
      to affect nucleic acid quantity and quality. DNA and RNA from selected FFPE and
      paired FF/FFPE specimens were used for exome and transcriptome analysis.
      Preparations of DNA Exome-Seq libraries was more challenging (29.5% success) than
      that of RNA-Seq libraries, presumably because of modifications to FFPE tissue
      derived DNA. Libraries could still be prepared from RNA isolated from two-decade
      old FFPE tissues. Data were analysed using the CLC Bio Genomics Workbench and
      revealed systematic differences between FF and FFPE tissue-derived nucleic acid
      libraries. In spite of this, pairwise analysis of DNA Exome-Seq data showed
      concordance for 70-80% of variants in FF and FFPE samples stored for fewer than
      three years. RNA-Seq data showed high correlation of expression profiles in
      FF/FFPE pairs (Pearson Correlations of 0.90 +/- 0.05), irrespective of storage
      time (up to 244 months) and tissue type. A common set of 1,494 genes was
      identified with expression profiles that were significantly different between
      paired FF and FFPE samples irrespective of tissue type. Our results are promising
      and suggest that NGS can be used to study FFPE specimens in both prospective and
      retrospective archive-based studies in which FF specimens are not available. 

PMID- 24878704
TI  - Author's response.

PMID- 24878703
TI  - Children and fluoride.

PMID- 24878705
TI  - Article questioned.

PMID- 24878706
TI  - Authors' response.

PMID- 24878707
TI  - The prevalence of caries and tooth loss among participants in the Hispanic
      Community Health Study/Study of Latinos.
AB  - BACKGROUND: The Hispanic and Latino population is projected to increase from 16.7
      percent to 30.0 percent by 2050. Previous U.S. national surveys had minimal
      representation of Hispanic and Latino participants other than Mexicans, despite
      evidence suggesting that Hispanic or Latino country of origin and degree of
      acculturation influence health outcomes in this population. In this article, the
      authors describe the prevalence and mean number of cavitated, decayed and filled
      surfaces, missing teeth and edentulism among Hispanics and Latinos of different
      national origins. METHODS: Investigators in the Hispanic Community Health
      Study/Study of Latinos (HCHS/SOL)-a multicenter epidemiologic study funded by the
      National Heart, Lung, and Blood Institute with funds transferred from six other
      institutes, including the National Institute of Dental and Craniofacial Research
      conducted in-person examinations and interviews with more than 16,000
      participants aged 18 to 74 years in four U.S. cities between March 2008 and June
      2011. The investigators identified missing, filled and decayed teeth according to
      a modified version of methods used in the National Health and Nutrition
      Examination Survey. The authors computed prevalence estimates (weighted
      percentages), weighted means and standard errors for measures. RESULTS: The
      prevalence of decayed surfaces ranged from 20.2 percent to 35.5 percent,
      depending on Hispanic or Latino background, whereas the prevalence of decayed and
      filled surfaces ranged from 82.7 percent to 87.0 percent, indicating substantial
      amounts of dental treatment. The prevalence of missing teeth ranged from 49.8
      percent to 63.8 percent and differed according to Hispanic or Latino background.
      Significant differences in the mean number of decayed surfaces, decayed or filled
      surfaces and missing teeth according to Hispanic and Latino background existed
      within each of the age groups and between women and men. CONCLUSIONS: Oral health
      status differs according to Hispanic or Latino background, even with adjustment
      for age, sex and other characteristics. PRACTICAL IMPLICATIONS: These data
      indicate that Hispanics and Latinos in the United States receive restorative
      dental treatment and that practitioners should consider the association between
      Hispanic or Latino origin and oral health status. This could mean that dental
      practices in areas dominated by patients from a single Hispanic or Latino
      background can anticipate a practice based on a specific pattern of treatment
      needs.

PMID- 24878708
TI  - The time efficiency of intraoral scanners: an in vitro comparative study.
AB  - BACKGROUND: Although intraoral scanners are known to have good accuracy in
      computer-aided impression making (CAIM), their effect on time efficiency is not.
      Little is known about the time required to make a digital impression. The purpose
      of the authors' in vitro investigation was to evaluate the time efficiency of
      intraoral scanners. METHODS: The authors used three different intraoral scanners
      to digitize a single abutment (scenario 1), a short-span fixed dental prosthesis
      (scenario 2) and a full-arch prosthesis preparation (scenario 3). They measured
      the procedure durations for the several scenarios and compiled and contrasted the
      procedure durations for three conventional impression materials. RESULTS: The
      mean total procedure durations for making digital impressions of scenarios 1, 2
      and 3 were as much as 5 minutes 57 seconds, 6 minutes 57 seconds, and 20 minutes
      55 seconds, respectively. Results showed statistically significant differences
      between all scanners (P < .05), except Lava (3M ESPE, St. Paul, Minn.) and iTero
      with foot pedal (Align Technology, San Jose, Calif.) for scenario 1, CEREC
      (Sirona, Bensheim, Germany) and CEREC with foot pedal for scenario 2, and iTero
      and iTero with foot pedal for scenarios 2 and 3. The compiled procedure durations
      for making conventional impressions in scenarios 1 and 2 ranged between 18
      minutes 15 seconds and 27 minutes 25 seconds; for scenario 3, they ranged between
      21 minutes 25 seconds and 30 minutes 25 seconds. CONCLUSIONS: The authors found
      that CAIM was significantly faster for all tested scenarios. This suggests that
      CAIM might be beneficial in establishing a more time-efficient work flow.
      PRACTICAL IMPLICATIONS: On the basis of the results of this in vitro study, the
      authors found CAIM to be superior regarding time efficiency in comparison with
      conventional approaches and might accelerate the work flow of making impressions.

PMID- 24878709
TI  - Sodium hypochlorite-related injury with chronic pain sequelae.
AB  - BACKGROUND: A 29-year-old woman visited a general dental residency clinic with a
      complaint of severe aching and burning facial pain with occasional sharp stabbing
      pain and persistent numbness. The symptoms had been present for seven months
      after sudden onset during endodontic irrigation with sodium hypchlorite. She was
      evaluated and treated by one of the authors, who was trained in orofacial pain
      management. CASE DESCRIPTION: The patient reported experiencing debilitating
      symptoms since the hypochlorite injury. She had been treated with
      methylprednisolone followed by antiseizure, anti-inflammatory and opioid
      medications prescribed by a neurologist. Examination and testing revealed static
      and dynamic mechanical allodynia along with neurological deficits on the left
      side of the face, implicating both peripheral and central pain mechanisms. The
      orofacial pain clinician made a diagnosis of peripheral painful traumatic
      trigeminal neuropathy involving all three branches of the left trigeminal nerve.
      The addition of an oral neurosensory stent and modification of medications
      reduced the patient's pain, resulting in improved function and quality of life.
      PRACTICAL IMPLICATIONS: Sodium hypochlorite irrigation may lead to injury and
      persistent neuropathic pain. Diagnosis and management of chronic orofacial pain
      require an understanding of pain mechanisms and appropriate treatment options. A
      multidisciplinary approach with clear communication among the general dentist,
      dental specialists, primary care physician and medical specialists often is
      necessary.

PMID- 24878710
TI  - A method of determining the presence of blood in and on a dental needle after the
      administration of local anesthetic.
AB  - BACKGROUND: In the study reported in this article, the authors aimed to
      demonstrate the presence of blood on the surface and in the lumen of two gauges
      of dental needles after administration of local anesthetic (LA) by using three LA
      administering techniques normally used for the extraction of teeth. METHODS: The
      authors obtained standardized photographs of 200 urine dipsticks after moistening
      the dipstick's chemical pads for blood with the first drop of liquid discharged
      from the needle lumen after LA administration. Using the histogram function of a
      software program, the authors analyzed differences in gray-scale values of the
      different blood parameters for the presence of blood. They used luminol spray to
      expose small quantities of blood on the surface of the needle after LA
      administration. RESULTS: Blood was identified at 39 percent in the lumen and at
      16 percent on the surface of the needles when analyzed after LA administration.
      CONCLUSIONS: With the method used, it was possible to demonstrate and quantify
      the percentage of blood present in the lumen of needles (39 percent) after the
      administration of dental LA. Furthermore, the technique was adequately sensitive
      for demonstrating the quantity of blood in two needles of different diameters.
      PRACTICAL IMPLICATIONS: By demonstrating the presence, as well as quantifying the
      percentage, of blood on two dental needles of different gauges after the
      administration of LA, dental health care workers can be motivated to report
      needlestick injuries and to follow the approved protocols recommended by their
      institutions.

PMID- 24878711
TI  - Multiple brain abscesses in an immunocompetent patient after undergoing
      professional tooth cleaning.
AB  - BACKGROUND: Dental disorders and dental treatment are among the variety of causes
      of brain abscess. CASE DESCRIPTION: The authors present the case of a patient who
      developed multiple brain abscesses after undergoing professional tooth cleaning.
      The results of a diagnostic work-up ruled out an underlying immunodeficiency.
      After receiving neurosurgical intervention and intensive care treatment by means
      of local and intravenous antibiotics for 24 days, the patient was transferred to
      another hospital for rehabilitation. Six months after the treatment, the patient
      still had moderate residual paresis of the left leg. PRACTICAL IMPLICATIONS:
      Although it happens rarely, professional tooth cleaning may be considered a cause
      of brain abscesses even in otherwise healthy patients.

PMID- 24878712
TI  - The indications for third-molar extractions.
AB  - BACKGROUND: Defining the indications for third-molar extraction continues to be a
      topic of controversy. METHODS: The dentist's management of third molars commonly
      hinges on identifying the presence of symptoms or disease that clearly is
      attributable to the third molar. Use of a guide that serves as a systematic and
      unambiguous way to classify third molars has been advocated. RESULTS: Patients'
      symptoms are designated as present and attributable to the third molar (Sx+) or
      as absent (Sx-). In addition, clinical or radiographic evidence of disease is
      evaluated and designated as present (D+) or absent (D-). CONCLUSIONS: Evidence
      based clinical data developed from prospective investigations have shown that an
      asymptomatic third molar does not necessarily reflect the absence of disease.
      PRACTICAL IMPLICATIONS: Current data are not sufficient to refute or support
      prophylactic extraction versus active surveillance for the routine management of
      third molars that are asymptomatic and free of disease (group D). Although
      decisions regarding third-molar management usually are straightforward, the
      evidence supporting extraction versus retention of asymptomatic disease-free
      (group D) third molars is lacking. Active surveillance, a prescribed program of
      follow-up and reassessment at regular intervals are recommended for retained
      third molars rather than waiting for the onset of symptoms.

PMID- 24878713
TI  - Reduced odds of pulpal exposure when using incomplete caries removal in the
      treatment of dentinal cavitated lesions.

PMID- 24878714
TI  - Acute posttraumatic jaw pain.

PMID- 24878715
TI  - The importance of effective morning meetings.

PMID- 24878716
TI  - Differential regulation of the serotonin transporter by vesicle-associated
      membrane protein 2 in cells of neuronal versus non-neuronal origin.
AB  - The serotonin transporter (SERT) is a key regulator of serotonergic signalling as
      it mediates the re-uptake of synaptic serotonin into nerve terminals, thereby
      terminating or modulating its signal. It is well-known that SERT regulation is a
      dynamic process orchestrated by a wide array of proteins and mechanisms. However,
      molecular details on possible coordinated regulation of SERT activity and 5-HT
      release are incomplete. Here, we report that vesicle-associated membrane protein
      2 (VAMP2), a SNARE protein that mediates vesicle fusion with the plasma membrane,
      interacts with SERT. This was documented in vitro, through GST pull-down assays,
      by co-immunoprecipitation experiments on heterologous cells and rat hippocampal
      synaptosomes, and with FRET analysis in live transfected HEK-293 MSR cells. The
      related isoforms VAMP1 and VAMP3 also physically interact with SERT. However,
      comparison of the three VAMP isoforms shows that only VAMP2 possesses a
      functionally distinct role in relation to SERT. VAMP2 influences 5-HT uptake,
      cell surface expression and the delivery rate of SERT to the plasma membrane
      differentially in HEK-293 MSR and PC12 cells. Moreover, siRNA-mediated knock-down
      of endogenous VAMP2 reduces 5-HT uptake in CAD cells stably expressing low levels
      of heterologous SERT. Deletion and mutant analysis suggest a role for the isoform
      specific C-terminal domain of VAMP2 in regulating SERT function. Our data
      identify a novel interaction between SERT and a synaptic vesicle protein and
      support a link between 5-HT release and re-uptake. 

PMID- 24878719
TI  - Modeling the fallout from stabilized nuclear clouds using the HYSPLIT atmospheric
      dispersion model.
AB  - The Hybrid Single Particle Lagrangian Integrated Trajectory (HYSPLIT) model,
      developed by the National Oceanic and Atmospheric Administration's Air Resources
      Laboratory, has been configured to simulate the dispersion and deposition of
      nuclear materials from a surface-based nuclear detonation using publicly
      available information on nuclear explosions. Much of the information was obtained
      from "The Effects of Nuclear Weapons" by Glasstone and Dolan (1977). The model
      was evaluated against the measurements of nuclear fallout from six nuclear tests
      conducted between 1951 and 1957 at the Nevada Test Site using the global
      NCEP/NCAR Reanalysis Project (NNRP) and the Weather Research and Forecasting
      (WRF) meteorological data as input. The model was able to reproduce the general
      direction and deposition patterns using the coarse NNRP data with Figure of Merit
      in Space (FMS - the percent overlap between predicted and measured deposition
      patterns) scores in excess of 50% for four of six simulations for the smallest
      dose rate contour, with FMS scores declining for higher dose rate contours. When
      WRF meteorological data were used the FMS scores were 5-20% higher in five of the
      six simulations, especially at the higher dose rate contours. The one WRF
      simulation where the scores declined slightly (10-30%) was also the best scoring
      simulation when using the NNRP data. When compared with measurements of dose rate
      and time of arrival from the Town Data Base (Thompson et al., 1994), similar
      results were found with the WRF simulations providing better results for four of
      six simulations. The overall result was that the different plume simulations
      using WRF data had more consistent performance than the plume simulations using
      NNRP data fields. 

PMID- 24878717
TI  - Estimated environmental radionuclide transfer and deposition into outdoor
      swimming pools.
AB  - In 2011, a large radioactive discharge occurred at the Fukushima Daiichi nuclear
      power plant. This plant is located within a climatically temperate region where
      outdoor swimming pools are popular. Although it is relatively easy to
      decontaminate pools by refilling them with fresh water, it is difficult to
      maintain safe conditions given highly contaminated diurnal dust falls from the
      surrounding contaminated ground. Our objectives in this paper were to conduct
      daily radioactivity measurements, to determine the quantity of radioactive
      contaminants from the surrounding environment that invade outdoor pools, and to
      investigate the efficacy of traditional pool cleaners in removing radioactive
      contaminants. The depositions in the paper filterable particulates ranged from 0
      to 62,5 Bq/m(2)/day, with the highest levels found in the southern Tohoku
      District containing Fukushima Prefecture and in the Kanto District containing
      Tokyo Metro. They were approximately correlated with the ground contamination.
      Traditional pool cleaners eliminated 99% of contaminants at the bottom of the
      pool, reducing the concentration to 41 Bq/m(2) after cleaning. Authors
      recommended the deposition or the blown radionuclides into outdoor swimming pools
      must be considered into pool regulations when the environments exactly polluted
      with radionuclides. 

PMID- 24878718
TI  - Indoor radon measurements in the uranium regions of Poli and Lolodorf, Cameroon.
AB  - The objective of this work is to carry out indoor radon measurements in the
      uranium regions of Poli and Lolodorf in which lie the uranium deposits of Kitongo
      and Lolodorf, prior to their impending exploitation. The indoor radon
      concentration was measured in 103 and 50 dwellings located respectively in Poli
      and Lolodorf using E-PERM electret chamber detectors. Indoor radon distributions
      in Poli and Lolodorf follow the lognormal law. Radon concentrations range
      respectively in Poli and Lolodorf between 29 and 2240 Bq m(-3) and 24-4390 Bq m(
      3) with corresponding median values of 165 Bq m(-3) and 331 Bq m(-3).
      Corresponding arithmetic and geometric means are respectively 294 Bq m(-3) and
      200 Bq m(-3) for the uranium region of Poli, 687 Bq m(-3) and 318 Bq m(-3) for
      the uranium region of Lolodorf. For the uranium region of Poli, 80% of dwellings
      have radon concentration above the reference level of 100 Bq m(-3) and 20% of
      dwellings show a radon concentration above 300 Bq m(-3). For the uranium region
      of Lolodorf, 80% of dwellings have radon concentration above 100 Bq m(-3) and 50%
      of dwellings show a radon concentration above 300 Bq m(-3). Thus radon monitoring
      and mitigation plan are required to better protect people against harmful effects
      of radon. 

PMID- 24878722
TI  - Computational methods for omics data.

PMID- 24878720
TI  - A gene-based analysis of variants in the serum/glucocorticoid regulated kinase
      (SGK) genes with blood pressure responses to sodium intake: the GenSalt Study.
AB  - BACKGROUND: Serum and glucocorticoid regulated kinase (SGK) plays a critical role
      in the regulation of renal sodium transport. We examined the association between
      SGK genes and salt sensitivity of blood pressure (BP) using single-marker and
      gene-based association analysis. METHODS: A 7-day low-sodium (51.3 mmol
      sodium/day) followed by a 7-day high-sodium intervention (307.8 mmol sodium/day)
      was conducted among 1,906 Chinese participants. BP measurements were obtained at
      baseline and each intervention using a random-zero sphygmomanometer. Additive
      associations between each SNP and salt-sensitivity phenotypes were assessed using
      a mixed linear regression model to account for family dependencies. Gene-based
      analyses were conducted using the truncated p-value method. The Bonferroni-method
      was used to adjust for multiple testing in all analyses. RESULTS: In single
      marker association analyses, SGK1 marker rs2758151 was significantly associated
      with diastolic BP (DBP) response to high-sodium intervention (P = 0.0010). DBP
      responses (95% confidence interval) to high-sodium intervention for genotypes
      C/C, C/T, and T/T were 2.04 (1.57 to 2.52), 1.79 (1.42 to 2.16), and 0.85 (0.30
      to 1.41) mmHg, respectively. Similar trends were observed for SBP and MAP
      responses although not significant (P = 0.15 and 0.0026, respectively). In
      addition, gene-based analyses demonstrated significant associations between SGK1
      and SBP, DBP and MAP responses to high sodium intervention (P = 0.0002, 0.0076,
      and 0.00001, respectively). Neither SGK2 nor SGK3 were associated with the salt
      sensitivity phenotypes in single-maker or gene-based analyses. CONCLUSIONS: The
      current study identified association of the SGK1 gene and BP salt-sensitivity in
      the Han Chinese population. Further studies are warranted to identify causal SGK1
      gene variants.

PMID- 24878721
TI  - Increased plasma YKL-40/chitinase-3-like-protein-1 is associated with endothelial
      dysfunction in obstructive sleep apnea.
AB  - PURPOSE: Obstructive sleep apnea (OSA) is a common disorder affecting 15-24% of
      the adults and is associated with increased risk of hypertension and
      atherosclerosis. The exact mechanisms underlying hypertension in OSA are not
      entirely clear. YKL-40/Chitinase-3-like protein-1 is a circulating moiety with
      roles in injury, repair and angiogenesis that is dysregulated in atherosclerosis
      and a number of other diseases. We sought to determine the role of YKL-40 in
      endothelial dysfunction and hypertension in OSA. METHODS: We studies 23
      normotensive OSA (N-OSA) and 14 hypertensive OSA (H-OSA) without diabetes and
      apparent cardiovascular disease. Endothelial-dependent nitric oxide-mediated
      vasodilatory capacity was assessed by flow-mediated vasodilation (FMD). YKL-40,
      vascular endothelial growth factor (VEGF) and the soluble form of VEGF receptor-1
      or sFlt-1 were measured in plasma using ELISA methodology. RESULTS: N-OSA
      subjects aged 49.1 +/- 2.3 years and H-OSA aged 51.3 +/- 1.9 years with BMI 36.1
      +/- 1.6 and 37.6 +/- 1.9 kg/m(2), respectively. The apnea-hypopnea index (AHI)
      was 41 +/- 5 events/hr in N-OSA and 46 +/- 6 in H-OSA with comparable degree of
      oxygen desaturations during sleep. FMD was markedly impaired in H-OSA (8.3% +/-
      0.8) compared to N-OSA (13.2% +/- 0.6, P<0.0001). Plasma YKL-40 was significantly
      elevated in H-OSA (55.2 +/- 7.9 ng/ml vs. 35.6 +/- 4.2 ng/ml in N-OSA, P = 0.02)
      and had an inverse relationship with FMD (r = -0.52, P = 0.013). There was a
      significant positive correlation between sFlt-1/VEGF, a measure of decreased VEGF
      availability, and YKL-40 (r = 0.42, P = 0.04). CONCLUSION: The levels of plasma
      YKL-40 were elevated in H-OSA group and inversely correlated with the endothelial
      dependent vasodilatory capacity whereas there was a positive correlation between
      sFlt-1/VEGF and YKL-40. These findings suggest that YKL-40 is dysregulated, in
      part, due to perturbation of VEGF signaling, and may contribute to endothelial
      dysfunction and hypertension in OSA.

PMID- 24878723
TI  - A comparison of microRNA sequencing reproducibility and noise reduction using
      mirVana and TRIzol isolation methods.
AB  - MicroRNAseq (miRNAseq) is a form of RNAseq technology that has become an
      increasingly popular alternative to miRNA expression profiling. Unlike messenger
      RNA (mRNA), miRNA extraction can be difficult, and sequencing such small RNA can
      also be problematic. We designed a study to test the reproducibility of miRNAseq
      technology and the performance of the two popular miRNA isolation methods,
      mirVana and TRIzol, by sequencing replicated samples using microRNA isolated with
      each kit. Through careful analysis of our data, we found excellent repeatability
      of miRNAseq technology. The mirVana method performed better than TRIzol in terms
      of useful reads sequenced, number of miRNA identified, and reproducibility.
      Finally, we identified a baseline noise level for miRNAseq technology; this
      baseline noise level can be used as a filter in future miRNAseq studies. 

PMID- 24878724
TI  - Classification of T cell movement tracks allows for prediction of cell function.
AB  - Using a unique combination of visual, statistical, and data mining methods, we
      tested the hypothesis that an immune cell's movement pattern can convey key
      information about the cell's function, antigen specificity, and environment. We
      applied clustering, statistical tests, and a support vector machine (SVM) to
      assess our ability to classify different datasets of imaged flouresently labelled
      T cells in mouse liver. We additionally saw clusters of different movement
      patterns of T cells of identical antigenic specificity. We found that the
      movement patterns of T cells specific and non-specific for malaria parasites are
      differentiable with 72% accuracy, and that specific cells have a higher tendency
      to move towards the parasite than non-specific cells. Movements of antigen
      specific T cells in uninfected mice vs. infected mice were differentiable with
      69.8% accuracy. We additionally saw clusters of different movement patterns of T
      cells of identical antigenic specificity. We concluded that our combination of
      methods has the potential to advance the understanding of cell movements in vivo.

PMID- 24878727
TI  - Localisation of Drosophila embryos using active contours in channel spaces.
AB  - In this paper, we introduce an active contour based scheme to localise Drosophila
      embryos in RGB images. An active contour (initiated as a closed one) maybe
      converge to an open contour, e.g., in the case that a targeting embryo is touched
      by a neighbouring one. We propose an algorithmic strategy to detect and restore
      open active contours. The experiment results show the promise of the proposed
      scheme. 

PMID- 24878725
TI  - BOTUX: bayesian-like operational taxonomic unit examiner.
AB  - Bayesian-like operational taxonomic unit examiner (BOTUX) is a new tool for the
      classification of 16S rRNA gene sequences into operational taxonomic units (OTUs)
      that addresses the problem of overestimation caused by errors introduced during
      PCR amplification and DNA sequencing steps. BOTUX utilises a grammar-based
      assignment strategy, where Bayesian models are built from each word of a given
      length (e.g., 8-mers). de novo analysis is possible with BOTUX as it does not
      require a training set, and updates probabilistic models as new sequences are
      recruited to an OTU. In benchmarking tests performed with real and simulated
      datasets of 16S rDNA sequences, BOTUX accurately identifies OTUs with comparable
      or better clustering efficiency and lower execution times than other OTU
      algorithms tested. BOTUX is the only OTU classifier, which allows incremental
      analysis of large datasets, and is also adept in clustering both 454 and Illumina
      datasets in a reasonable timeframe. 

PMID- 24878726
TI  - The centrality of cancer proteins in human protein-protein interaction network: a
      revisit.
AB  - Topological analysis of protein-protein interaction (PPI) networks has been
      widely applied to the investigation on cancer mechanisms. However, there is still
      a debate on whether cancer proteins exhibit more topological centrality compared
      to the other proteins in the human PPI network. To resolve this debate, we first
      identified four sets of human proteins, and then mapped these proteins into the
      yeast PPI network by homologous genes. Finally, we compared these proteins'
      properties in human and yeast PPI networks. Experiments over two real datasets
      demonstrated that cancer proteins tend to have higher degree and smaller
      clustering coefficient than non-cancer proteins. Experimental results also
      validated that cancer proteins have larger betweenness centrality compared to the
      other proteins on the STRING dataset. However, on the BioGRID dataset, the
      average betweenness centrality of cancer proteins is larger than that of disease
      and control proteins, but smaller than that of essential proteins. 

PMID- 24878728
TI  - Aeromonas phages encode tRNAs for their overused codons.
AB  - The GC-rich bacterial species, Aeromonas salmonicida, is parasitised by both GC
      rich phages (Aeromonas phages - phiAS7 and vB_AsaM-56) and GC-poor phages
      (Aeromonas phages - 25, 31, 44RR2.8t, 65, Aes508, phiAS4 and phiAS5). Both the GC
      rich Aeromonas phage phiAS7 and Aeromonas phage vB_AsaM-56 have nearly identical
      codon usage bias as their host. While all the remaining seven GC-poor Aeromonas
      phages differ dramatically in codon usage from their GC-rich host. Here, we
      investigated whether tRNA encoded in the genome of Aeromonas phages facilitate
      the translation of phage proteins. We found that tRNAs encoded in the phage
      genome correspond to synonymous codons overused in the phage genes but not in the
      host genes. 

PMID- 24878729
TI  - Differential Shannon entropy and differential coefficient of variation:
      alternatives and augmentations to differential expression in the search for
      disease-related genes.
AB  - Differential expression has been a standard tool for analysing case-control
      transcriptomic data since the advent of microarray technology. It has proved
      invaluable in characterising the molecular mechanisms of disease. Nevertheless,
      the expression profile of a gene across samples can be perturbed in ways that
      leave the expression level unaltered, while a biological effect is nonetheless
      present. This paper describes and analyses differential Shannon entropy and
      differential coefficient of variation, two alternate techniques for identifying
      genes of interest. Ontological analysis across 16 human disease datasets
      demonstrates that these alternatives are effective at identifying disease-related
      genes not found by mere differential expression alone. Because the two alternate
      techniques are based on somewhat different mathematical formulations, they tend
      to produce somewhat different gene lists. Moreover, each may pinpoint genes
      completely overlooked by the other. Thus, measures of entropy and variation can
      be used to replace or better yet augment standard differential expression
      computations. 

PMID- 24878730
TI  - Correcting imbalanced reads coverage in bacterial transcriptome sequencing with
      extreme deep coverage.
AB  - High throughput bacterial RNA-Seq experiments can generate extremely high and
      imbalanced sequencing coverage. Over- or under-estimation of gene expression
      levels will hinder accurate gene differential expression analysis. Here we
      evaluated strategies to identify expression differences of genes with high
      coverage in bacterial transcriptome data using either raw sequence reads or
      unique reads with duplicate fragments removed. In addition, we proposed a
      generalised linear model (GLM) based approach to identify imbalance in read
      coverage based on sequence compositions. Our results show that analysis using raw
      reads identifies more differentially expressed genes with more accurate fold
      change than using unique reads. We also demonstrate the presence of sequence
      composition related biases that are independent of gene expression levels and
      experimental conditions. Finally, genes that still show strong coverage imbalance
      after correction were tagged using statistical approach. 

PMID- 24878731
TI  - Supervised method for periodontitis phenotypes prediction based on microbial
      composition using 16S rRNA sequences.
AB  - Microbes play an important role on human health, however, little is known on
      microbes in the past decades for the limitation of culture-based techniques.
      Recently, with the development of next-generation sequencing (NGS) technologies,
      it is now possible to sequence millions of sequences directly from environments
      samples, and thus it supplies us a sight to probe the hidden world of microbial
      communities and detect the associations between microbes and diseases. In the
      present work, we proposed a supervised learning-based method to mine the
      relationship between microbes and periodontitis with 16S rRNA sequences. The
      jackknife accuracy is 94.83% and it indicated the method can effectively predict
      disease status. These findings not only expand our understanding of the
      association between microbes and diseases but also provide a potential approach
      for disease diagnosis and forensics. 

PMID- 24878732
TI  - Generic strategies for chemical space exploration.
AB  - The chemical universe of molecules reachable from a set of start compounds by
      iterative application of a finite number of reactions is usually so vast, that
      sophisticated and efficient exploration strategies are required to cope with the
      combinatorial complexity. A stringent analysis of (bio)chemical reaction
      networks, as approximations of these complex chemical spaces, forms the
      foundation for the understanding of functional relations in Chemistry and
      Biology. Graphs and graph rewriting are natural models for molecules and
      reactions. Borrowing the idea of partial evaluation from functional programming,
      we introduce partial applications of rewrite rules. A framework for the
      specification of exploration strategies in graph-rewriting systems is presented.
      Using key examples of complex reaction networks from carbohydrate chemistry we
      demonstrate the feasibility of this high-level strategy framework. While being
      designed for chemical applications, the framework can also be used to emulate
      higher-level transformation models such as illustrated in a small puzzle game. 

PMID- 24878733
TI  - Automatic cell segmentation in strongly agglomerated cell networks for different
      cell types.
AB  - This paper presents a method of separating cells that are connected to each other
      forming clusters. The difference to many other publications covering similar
      topics is that the cell types we are dealing with form clusters of highly varying
      morphology. An advantage of our method is that it can be universally used for
      different cell types. The segmentation method is based on a growth simulation
      starting from the nuclei areas. To start the evaluation, the cells need to be
      made visible with a histological stain, in our case with the May-Grunwald
      solution. After the staining process has been completed, the nuclei areas can be
      distinguished from the other cell areas by a histogram backprojection algorithm.
      The presented method can, in addition to histological stained cells, also be
      applied to fluorescent-stained cells. 

PMID- 24878734
TI  - P56(lck) kinase inhibitor studies: a 3D QSAR approach towards designing new drugs
      from flavonoid derivatives.
AB  - Comparative molecular field analysis (CoMFA) and comparative molecular similarity
      indices analysis (CoMSIA) based on 3D-QSAR (3D-quantitative structure activity
      relationship) studies were carried out on 97 flavonoid derivatives as potent
      P56(lck) protein tyrosine kinase inhibitors. The best prediction was obtained
      with CoMFA standard model (q2 = 0.838, r2 = 0.948) using steric, electrostatic
      along with CoMSIA standard model (q2 = 0.714, r2 = 0.921) using steric,
      electrostatic, hydrophobic, hydrogen bond donor and acceptor fields. Of the 97
      molecules a training set of 76 compounds and the predictive ability of the QSAR
      model were assessed employing a test set of 21 compounds. The resulting CoMFA and
      CoMSIA contour maps were used to identify the structural features relevant to the
      biological activity in this series of flavonoid derivatives, based upon which we
      identified and designed 10 novel molecules that showed superior inhibitory
      activity against P56(lck) protein which shed new light on effective therapeutic
      agents against these classes of enzymes. 

PMID- 24878735
TI  - Prediction of in vivo joint mechanics of an artificial knee implant using rigid
      multi-body dynamics with elastic contacts.
AB  - Lower extremity musculoskeletal computational models play an important role in
      predicting joint forces and muscle activation simultaneously and are valuable for
      investigating functional outcomes of the implants. However, current computational
      musculoskeletal models of total knee replacement rarely consider the bearing
      surface geometry of the implant. Therefore, these models lack detailed
      information about the contact loading and joint motion which are important
      factors for evaluating clinical performances. This study extended a rigid multi
      body dynamics simulation of a lower extremity musculoskeletal model to
      incorporate an artificial knee joint, based upon a novel force-dependent
      kinematics method, and to characterize the in vivo joint contact mechanics during
      gait. The developed musculoskeletal total knee replacement model integrated the
      rigid skeleton multi-body dynamics and the flexible contact mechanics of the
      tibiofemoral and patellofemoral joints. The predicted contact forces and muscle
      activations are compared against those in vivo measurements obtained from a
      single patient with good agreements for the medial contact force (root-mean
      square error = 215 N, rho = 0.96) and lateral contact force (root-mean-square
      error = 179 N, rho = 0.75). Moreover, the developed model also predicted the
      motion of the tibiofemoral joint in all degrees of freedom. This new model
      provides an important step toward the development of a realistic dynamic
      musculoskeletal total knee replacement model to predict in vivo knee joint motion
      and loading simultaneously. This could offer a better opportunity to establish a
      robust virtual modeling platform for future pre-clinical assessment of knee
      prosthesis designs, surgical procedures and post-operation rehabilitation.

PMID- 24878736
TI  - Experimental validation of a new biphasic model of the contact mechanics of the
      porcine hip.
AB  - Hip models that incorporate the biphasic behaviour of articular cartilage can
      improve understanding of the joint function, pathology of joint degeneration and
      effect of potential interventions. The aim of this study was to develop a
      specimen-specific biphasic finite element model of a porcine acetabulum
      incorporating a biphasic representation of the articular cartilage and to
      validate the model predictions against direct experimental measurements of the
      contact area in the same specimen. Additionally, the effect of using a different
      tension-compression behaviour for the solid phase of the articular cartilage was
      investigated. The model represented different radial clearances and load
      magnitudes. The comparison of the finite element predictions and the experimental
      measurement showed good agreement in the location, size and shape of the contact
      area, and a similar trend in the relationship between contact area and load was
      observed. There was, however, a deviation of over 30% in the magnitude of the
      contact area, which might be due to experimental limitations or to
      simplifications in the material constitutive relationships used. In comparison
      with the isotropic solid phase model, the tension-compression solid phase model
      had better agreement with the experimental observations. The findings provide
      some confidence that the new biphasic methodology for modelling the cartilage is
      able to predict the contact mechanics of the hip joint. The validation provides a
      foundation for future subject-specific studies of the human hip using a biphasic
      cartilage model.

PMID- 24878739
TI  - Information dissemination analysis of different media towards the application for
      disaster pre-warning.
AB  - Knowing the information dissemination mechanisms of different media and having an
      efficient information dissemination plan for disaster pre-warning plays a very
      important role in reducing losses and ensuring the safety of human beings. In
      this paper we established models of information dissemination for six typical
      information media, including short message service (SMS), microblogs, news
      portals, cell phones, television, and oral communication. Then, the information
      dissemination capability of each medium concerning individuals of different ages,
      genders, and residential areas was simulated, and the dissemination
      characteristics were studied. Finally, radar graphs were used to illustrate
      comprehensive assessments of the six media; these graphs show directly the
      information dissemination characteristics of all media. The models and the
      results are essential for improving the efficiency of information dissemination
      for the purpose of disaster pre-warning and for formulating emergency plans which
      help to reduce the possibility of injuries, deaths and other losses in a
      disaster. 

PMID- 24878737
TI  - Structure of cellular ESCRT-III spirals and their relationship to HIV budding.
AB  - The ESCRT machinery along with the AAA+ ATPase Vps4 drive membrane scission for
      trafficking into multivesicular bodies in the endocytic pathway and for the
      topologically related processes of viral budding and cytokinesis, but how they
      accomplish this remains unclear. Using deep-etch electron microscopy, we find
      that endogenous ESCRT-III filaments stabilized by depleting cells of Vps4 create
      uniform membrane-deforming conical spirals which are assemblies of specific ESCRT
      III heteropolymers. To explore functional roles for ESCRT-III filaments, we
      examine HIV-1 Gag-mediated budding of virus-like particles and find that
      depleting Vps4 traps ESCRT-III filaments around nascent Gag assemblies.
      Interpolating between the observed structures suggests a new role for Vps4 in
      separating ESCRT-III from Gag or other cargo to allow centripetal growth of a
      neck constricting ESCRT-III spiral. 

PMID- 24878738
TI  - APOE epsilon4 is associated with disproportionate progressive hippocampal atrophy
      in AD.
AB  - OBJECTIVES: To investigate whether APOE epsilon4 carriers have higher hippocampal
      atrophy rates than non-carriers in Alzheimer's disease (AD), mild cognitive
      impairment (MCI) and controls, and if so, whether higher hippocampal atrophy
      rates are still observed after adjusting for concurrent whole-brain atrophy
      rates. METHODS: MRI scans from all available visits in ADNI (148 AD, 307 MCI, 167
      controls) were used. MCI subjects were divided into "progressors" (MCI-P) if
      diagnosed with AD within 36 months or "stable" (MCI-S) if a diagnosis of MCI was
      maintained. A joint multi-level mixed-effect linear regression model was used to
      analyse the effect of epsilon4 carrier-status on hippocampal and whole-brain
      atrophy rates, adjusting for age, gender, MMSE and brain-to-intracranial volume
      ratio. The difference in hippocampal rates between epsilon4 carriers and non
      carriers after adjustment for concurrent whole-brain atrophy rate was then
      calculated. RESULTS: Mean adjusted hippocampal atrophy rates in epsilon4 carriers
      were significantly higher in AD, MCI-P and MCI-S (p<=0.011, all tests) compared
      with epsilon4 non-carriers. After adjustment for whole-brain atrophy rate, the
      difference in mean adjusted hippocampal atrophy rate between epsilon4 carriers
      and non-carriers was reduced but remained statistically significant in AD and MCI
      P. CONCLUSIONS: These results suggest that the APOE epsilon4 allele drives
      atrophy to the medial-temporal lobe region in AD.

PMID- 24878740
TI  - Increase of hemoglobin levels by anti-IL-6 receptor antibody (tocilizumab) in
      rheumatoid arthritis.
AB  - OBJECTIVE: To compare the effect of tocilizumab (TCZ) with other biologic
      therapies in improving anemia of rheumatoid arthritis (RA) patients. METHODS: We
      compared the change of hemoglobin (Hb) levels in a cohort of 147 consecutive RA
      patients who were treated with biologics for more than 12 weeks. Twenty eight
      patients were treated with TCZ, and 119 patients were treated with biologics
      other than TCZ (87 with TNF inhibitors and 32 with abatacept). The change of Hb
      levels from baseline to week 12 was compared between the TCZ and the non-TCZ
      groups. We performed univariate and multivariate analyses with adjustment of
      potential confounders such as baseline characteristics, concomitant treatment,
      and the clinical response to treatment. RESULTS: Hb levels generally increased
      after biologic therapies both in the TCZ and the non-TCZ groups. The increase of
      Hb levels was greater in the TCZ group than in the non-TCZ groups (1.1 g/dL in
      the TCZ group vs 0.3 g/dL in the non-TCZ group, p = 0.009). Univariate analysis
      revealed that increase of Hb levels was also significantly associated with lower
      Hb, higher Low Hemoglobin Density, and higher CRP levels at baseline and greater
      reduction in the clinical disease activity index. TCZ therapy was significantly
      associated with the increase of Hb levels even after adjustment for these factors
      by multivariate analysis (p<0.001, effect size 0.08-0.12). CONCLUSION: TCZ
      therapy is an independent factor associated with the increase of Hb level after
      biologic therapies in RA patients. It will help in selecting appropriate
      biologics for RA patients with anemia.

PMID- 24878741
TI  - Actinobacillus pleuropneumoniae possesses an antiviral activity against porcine
      reproductive and respiratory syndrome virus.
AB  - Pigs are often colonized by more than one bacterial and/or viral species during
      respiratory tract infections. This phenomenon is known as the porcine respiratory
      disease complex (PRDC). Actinobacillus pleuropneumoniae (App) and porcine
      reproductive and respiratory syndrome virus (PRRSV) are pathogens that are
      frequently involved in PRDC. The main objective of this project was to study the
      in vitro interactions between these two pathogens and the host cells in the
      context of mixed infections. To fulfill this objective, PRRSV permissive cell
      lines such as MARC-145, SJPL, and porcine alveolar macrophages (PAM) were used. A
      pre-infection with PRRSV was performed at 0.5 multiplicity of infection (MOI)
      followed by an infection with App at 10 MOI. Bacterial adherence and cell death
      were compared. Results showed that PRRSV pre-infection did not affect bacterial
      adherence to the cells. PRRSV and App co-infection produced an additive
      cytotoxicity effect. Interestingly, a pre-infection of SJPL and PAM cells with
      App blocked completely PRRSV infection. Incubation of SJPL and PAM cells with an
      App cell-free culture supernatant is also sufficient to significantly block PRRSV
      infection. This antiviral activity is not due to LPS but rather by small
      molecular weight, heat-resistant App metabolites (<1 kDa). The antiviral activity
      was also observed in SJPL cells infected with swine influenza virus but to a much
      lower extent compared to PRRSV. More importantly, the PRRSV antiviral activity of
      App was also seen with PAM, the cells targeted by the virus in vivo during
      infection in pigs. The antiviral activity might be due, at least in part, to the
      production of interferon gamma. The use of in vitro experimental models to study
      viral and bacterial co-infections will lead to a better understanding of the
      interactions between pathogens and their host cells, and could allow the
      development of novel prophylactic and therapeutic tools. 

PMID- 24878742
TI  - A clip-domain serine proteinase homolog (SPH) in oriental river prawn,
      Macrobrachium nipponense provides insights into its role in innate immune
      response.
AB  - In this study, a clip-domain serine proteinase homolog designated as MnSPH was
      cloned and characterized from a freshwater prawn Macrobrachium nipponense. The
      full-length cDNA of MnSPH was 1897 bp and contained a 1701 bp open reading frame
      (ORF) encoding a protein of 566 amino acids, a 103 bp 5'-untranslated region, and
      a 93 bp 3'-untranslated region. Sequence comparison showed that the deduced amino
      acids of MnSPH shared 30-59% identity with sequences reported in other animals.
      Tissue distribution analysis indicated that the MnSPH transcripts were present in
      all detected tissues with highest in the hepatopancreas and ovary. The MnSPH mRNA
      levels in the developing ovary were stable at the initial three developmental
      stages, then increased gradually from stage IV (later vitellogenesis), and
      reached a maximum at stage VI (paracmasis). Furthermore, the expression of MnSPH
      mRNA in hemocytes was significantly up-regulated at 1.5 h, 6 h, 12 h and 48 h
      post Aeromonas hydrophila injection. The increased phenoloxidase activity also
      demonstrated a clear time-dependent pattern after A. hydrophila challenge. These
      results suggest that MnSPH participates in resisting to pathogenic microorganisms
      and plays a pivotal role in host defense against microbe invasion in M.
      nipponense.

PMID- 24878744
TI  - A case of acute myocarditis associated with Chlamydia trachomatis infection: role
      of cardiac MRI in the clinical management.
AB  - We report the case of a 32-year-old male with Chlamydia trachomatis infection and
      admitted with chest pain, signs of myocardial damage and coronary arteries free
      from significant atherosclerotic disease. Cardiac magnetic resonance imaging
      (MRI) documented imaging patterns of myocardial involvement suggestive of acute
      myocarditis, and repeated cardiac MRI examinations were used to define
      appropriate clinical management of the patient. In particular, the decision to
      submit the patient to an additional antibiotic course was based on evidence of
      persisting myocardial edema, while no further treatments were prescribed once
      these imaging findings disappeared. The case emphasizes the potential value of
      cardiac MRI as the only non-invasive modality currently available for evaluating
      the temporal evolution of myocardial involvement after acute myocarditis. 

PMID- 24878743
TI  - Dietary administration of Bacillus subtilis on hematology and non-specific
      immunity of Nile tilapia Oreochromis niloticus raised at different stocking
      densities.
AB  - An 84-day feeding trial was conducted to evaluate the effect of the dietary
      administration of Bacillus subtilis on the growth performance, body composition,
      intestinal probiotic recovery, hematology, and non-specific immunity of Nile
      tilapia (Oreochromis niloticus) raised at two stocking densities. Five hundred
      twenty male Nile tilapias (32.63 +/- 1.25 g) were distributed in 16,800-L tanks.
      The experimental design was completely randomized using four replications and a 2
      * 2 factorial scheme with two stocking densities (18.75 fish m(-3) 62.50 fish m(
      3)) and two diets (control and with probiotic). The probiotic-supplemented diet
      included 5 * 10(6) CFU g feed(-1). There were no significant differences (P >
      0.05) in the growth performance, body composition, and levels of cortisol and
      glucose between the animals fed with the control diet and the animals fed with
      the probiotic-supplemented diet. Differences in the growth performance were
      observed between the fish reared at different stocking densities; in particular,
      the fish raised at the high stocking density exhibited reduced weight gain, feed
      intake, and specific growth rate compared with those raised at the low stocking
      density. The B. subtilis remained viable after its inclusion in the feed,
      storage, and passage through the stomach, which demonstrations the feasibility of
      using this bacteria as a probiotic. Higher values (P < 0.05) in the plasma
      lysozyme levels and phagocytic activity were observed in the fish that received
      the probiotic-supplemented diet and reared at the high stocking density, but this
      difference was not observed in the fish raised at the low stocking density and
      fed the different diets. The administration of the probiotic caused decreases in
      the number of erythrocytes and the hematocrit level in the fish reared at the
      high stocking density, but these erythrocytes showed higher values of mean
      corpuscular hemoglobin. The stocking density was shown to be a stressor agent
      that causes a lower fish growth rate. The fish fed the control diet and raised at
      the high stocking density had lower lysozyme levels than the fish subjected to
      the other treatments. The inclusion of the probiotic bacteria B. subtilis at a
      concentration of 5 * 10(6) CFU g feed(-1) benefited the innate immune system of
      Nile tilapia by decreasing the stress associated with exposure to a high stocking
      density, increasing the mean corpuscular hemoglobin, and improving the innate
      immune system (lysozyme and phagocytic activities of macrophages).

PMID- 24878746
TI  - Associations of ECG interval prolongations with mortality among ESRD patients
      evaluated for renal transplantation.
AB  - BACKGROUND: It is unknown whether prolongation of electrocardiogram (ECG)
      intervals is associated with mortality in end-stage renal disease (ESRD) patients
      evaluated for renal transplantation. MATERIAL AND METHODS: We examined the
      relationship between 12-lead ECG interval measurements (PR >200 ms, QRS >110 ms,
      or QTC >450 ms) and the presence of none, 1, and 2 or more ECG interval
      prolongations with all-cause mortality in 930 adult ESRD patients evaluated for
      renal transplantation from August 2006 to October 2008 and followed through
      November 2010. RESULTS: A total of 108 (11.6%) patients died after a median
      follow-up of 3.1 years. A stepwise increase in all-cause mortality occurred among
      adult ESRD patients with prolongation of 1, and 2 or more ECG intervals. In
      adjusted analyses, the rate of death in patients with at least 1 ECG interval
      prolongation was 69% higher than that of patients with no ECG prolongations
      (HR=1.69; 95% CI: 1.05-2.73). Patients with 2 or more ECG interval prolongations
      had a 2.5-fold increased likelihood of dying vs. patients with no ECG interval
      prolongations (HR 2.53, 95% CI 1.38-4.82). CONCLUSIONS: ECG interval
      prolongations are associated with higher mortality in patients evaluated for
      renal transplantation. The ECG is a potentially important evaluative tool for
      risk assessment in this population.

PMID- 24878747
TI  - Spatio-temporal dynamics of maize yield water constraints under climate change in
      Spain.
AB  - Many studies have analyzed the impact of climate change on crop productivity, but
      comparing the performance of water management systems has rarely been explored.
      Because water supply and crop demand in agro-systems may be affected by global
      climate change in shaping the spatial patterns of agricultural production, we
      should evaluate how and where irrigation practices are effective in mitigating
      climate change effects. Here we have constructed simple, general models, based on
      biological mechanisms and a theoretical framework, which could be useful in
      explaining and predicting crop productivity dynamics. We have studied maize in
      irrigated and rain-fed systems at a provincial scale, from 1996 to 2009 in Spain,
      one of the most prominent "hot-spots" in future climate change projections. Our
      new approach allowed us to: (1) evaluate new structural properties such as the
      stability of crop yield dynamics, (2) detect nonlinear responses to climate
      change (thresholds and discontinuities), challenging the usual linear way of
      thinking, and (3) examine spatial patterns of yield losses due to water
      constraints and identify clusters of provinces that have been negatively affected
      by warming. We have reduced the uncertainty associated with climate change
      impacts on maize productivity by improving the understanding of the relative
      contributions of individual factors and providing a better spatial comprehension
      of the key processes. We have identified water stress and water management
      systems as being key causes of the yield gap, and detected vulnerable regions
      where efforts in research and policy should be prioritized in order to increase
      maize productivity. 

PMID- 24878745
TI  - Learning to eat vegetables in early life: the role of timing, age and individual
      eating traits.
AB  - Vegetable intake is generally low among children, who appear to be especially
      fussy during the pre-school years. Repeated exposure is known to enhance intake
      of a novel vegetable in early life but individual differences in response to
      familiarisation have emerged from recent studies. In order to understand the
      factors which predict different responses to repeated exposure, data from the
      same experiment conducted in three groups of children from three countries (n =
      332) aged 4-38 m (18.9+/-9.9 m) were combined and modelled. During the
      intervention period each child was given between 5 and 10 exposures to a novel
      vegetable (artichoke puree) in one of three versions (basic, sweet or added
      energy). Intake of basic artichoke puree was measured both before and after the
      exposure period. Overall, younger children consumed more artichoke than older
      children. Four distinct patterns of eating behaviour during the exposure period
      were defined. Most children were "learners" (40%) who increased intake over time.
      21% consumed more than 75% of what was offered each time and were labelled "plate
      clearers". 16% were considered "non-eaters" eating less than 10 g by the 5th
      exposure and the remainder were classified as "others" (23%) since their pattern
      was highly variable. Age was a significant predictor of eating pattern, with
      older pre-school children more likely to be non-eaters. Plate-clearers had higher
      enjoyment of food and lower satiety responsiveness than non-eaters who scored
      highest on food fussiness. Children in the added energy condition showed the
      smallest change in intake over time, compared to those in the basic or sweetened
      artichoke condition. Clearly whilst repeated exposure familiarises children with
      a novel food, alternative strategies that focus on encouraging initial tastes of
      the target food might be needed for the fussier and older pre-school children. 

PMID- 24878749
TI  - Use of aged refuse-based bioreactor/biofilter for landfill leachate treatment.
AB  - Sanitary landfilling is a proven way for disposal of municipal solid waste (MSW)
      in developed countries in general and in developing countries in particular,
      owing to its low immediate costs. On the other hand, landfilling is a matter of
      concern due to its generation of heavily polluted leachate. Landfill leachate
      becomes more refractory with time and is very difficult to treat using
      conventional biological processes. The aged refuse-based bioreactor/biofilter
      (ARB) has been shown to be a promising technology for the removal of various
      pollutants from landfill leachate and validates the principle of waste control by
      waste. Based on different environmental and operational factors, many researchers
      have reported remarkable pollutant removal efficiencies using ARB. This paper
      gives an overview of various types of ARBs used; their efficiencies; and certain
      factors like temperatures, loading rates, and aerobic/anaerobic conditions which
      affect the performance of ARBs in eliminating pollutants from leachate. Treating
      leachate by ARBs has been proved to be more cost-efficient, environment friendly,
      and simple to operate than other traditional biological techniques. Finally,
      future research and developments are also discussed.

PMID- 24878748
TI  - Deletion of ARNT (Aryl hydrocarbon receptor nuclear translocator) in beta-cells
      causes islet transplant failure with impaired beta-cell function.
AB  - BACKGROUND: Replacing beta-cells by islet-transplantation can cure type 1
      diabetes, but up to 70% of beta-cells die within 10 days of transplantation. ARNT
      (Aryl hydrocarbon Receptor Nuclear Translocator) regulates beta-cell function,
      and potentially survival. Lack of ARNT impairs the ability of beta-cells to
      respond to physiological stress and potentiates the onset of diabetes, but the
      exact role of ARNT in graft outcome is unknown. AIM: To investigate the effect of
      beta-cell deletion of ARNT on graft outcomes. METHODS: Islets were isolated from
      donor mice which had beta-cell specific ARNT-deletion (beta-ARNT) or littermate
      floxed controls. The islets were transplanted into diabetic SCID recipients in
      ratios of (a) 3 donors: 1 recipient, (b) 1 donor: 1 recipient or (c) 1/2 of the
      islets from 1 donor: 1 recipient. After 28 days, the kidney containing the graft
      was removed (nephrectomy) to exclude regeneration of the endogenous pancreas.
      RESULTS: In the supra-physiological-mass model (3:1), both groups achieved
      reasonable glycaemia, with slightly higher levels in beta-ARNT-recipients. In
      adequate-mass model (1:1), beta-ARNT recipients had poor glucose control versus
      floxed-control recipients and versus the beta-ARNT donors. In the low-beta-cell
      mass model (1/2:1) beta-ARNT transplants completely failed, whereas controls had
      good outcomes. Unexpectedly, there was no difference in the graft insulin content
      or beta-cell mass between groups indicating that the defect was not due to early
      altered beta-cell survival. CONCLUSION: Outcomes for islet transplants lacking
      beta-cell ARNT were poor, unless markedly supra-physiological masses of islets
      were transplanted. In the 1:1 transplant model, there was no difference in beta
      cell volume. This is surprising because transplants of islets lacking one of the
      ARNT-partners HIF-1alpha have increased apoptosis and decreased islet volume.
      ARNT also partners HIF-2alpha and AhR (aryl hydrocarbon receptor) to form active
      transcriptional complexes, and further work to understand the roles of HIF-2alpha
      and AhR in transplant outcomes is needed.

PMID- 24878750
TI  - Clostridium butyricum reduce lipogenesis through bacterial wall components and
      butyrate.
AB  - Intervention strategies for obesity are global issues that require immediate
      attention. The objective of this study was to assess the possibility that
      Clostridium butyricum and its potential components could reduce lipogenesis. Co
      culture experiments of Caco-2 cells and 1 * 10(6), 1 * 10(7), and 1 * 10(8)
      CFU/ml of C. butyricum were set up to monitor the cytotoxicity of C. butyricum
      and the changes of angiopoietin-like protein 4 (ANGPTL4) mRNA expression. It was
      found that cell viability was not affected by C. butyricum, and ANGPTL4 mRNA
      expression in Caco-2 cells was highly induced by 1 * 10(7) CFU/ml of C.
      butyricum. Co-culture experiment of Caco-2 cells and potential components of C.
      butyricum were set up to monitor any ensuing alteration in ANGPTL4. It was
      observed that bacterial wall components and potentially secreted factors from C.
      butyricum could induce ANGPTL4 mRNA expression and protein secretion. To
      determine whether butyrate could affect the ANGPTL4 production in Caco-2 cells,
      the role of monocarboxylate transporter 1 (MCT1) in mediating potentially
      secreted factors from C. butyricum-induced ANGPTL4 production in Caco-2 cells and
      the effect of 0.1 mM of butyrate on ANGPTL4 production in Caco-2 cells were
      investigated. It is confirmed that butyrate was the factor secreted by C.
      butyricum to stimulate ANGPTL4 production. Besides, the soluble factors secreted
      by live C. butyricum-Caco-2 cells interaction, bacterial wall components-Caco-2
      cells interaction, and the main metabolites butyrate-Caco-2 cells interaction
      reduced lipogenic gene expression in HepG2 cells. In conclusion, 1 * 10(7) CFU/ml
      of C. butyricum could reduce lipogenesis through the bacterial wall components
      and the metabolites such as butyrate.

PMID- 24878751
TI  - Enhancement of glycerol utilization ability of Ralstonia eutropha H16 for
      production of polyhydroxyalkanoates.
AB  - Ralstonia eutropha H16 is a well-studied bacterium with respect to biosynthesis
      of polyhydroxyalkanoates (PHAs), which has attracted attentions as biodegradable
      bio-based plastics. However, this strain shows quite poor growth on glycerol of
      which bulk supply has been increasing as a major by-product of biodiesel
      industries. This study examined enhancement of glycerol assimilation ability of
      R. eutropha H16 by introduction of the genes of aquaglyceroporin (glpF) and
      glycerol kinase (glpK) from Escherichia coli. Although introduction of glpFK Ec
      into the strain H16 using a multi-copy vector was not successful, a recombinant
      strain possessing glpFK Ec within the chromosome showed much faster growth on
      glycerol than H16. Further analyses clarified that weak expression of glpK Ec
      alone allowed to establish efficient glycerol assimilation pathway, indicating
      that the poor growth of H16 on glycerol was caused by insufficient kination
      activity to glycerol, as well as this strain had a potential ability for uptake
      of extracellular glycerol. The engineered strains expressing glpFK Ec or glpK Ec
      produced large amounts of poly[(R)-3-hydroxybutyrate] [P(3HB)] from glycerol with
      much higher productivity than H16. Unlike other glycerol-utilizable wild strains
      of R. eutropha, the H16-derived engineered strains accumulated P(3HB) with no
      significant decrease in molecular weights on glycerol, and the polydispersity
      index of the glycerol-based P(3HB) synthesized by the strains expressing glpFK Ec
      was lower than those by the parent strains. The present study demonstrated
      possibility of R. eutropha H16-based platform for production of useful compounds
      from inexpensive glycerol.

PMID- 24878752
TI  - Metabolic engineering of Propionibacterium freudenreichii: effect of expressing
      phosphoenolpyruvate carboxylase on propionic acid production.
AB  - Propionic acid is currently produced mainly via petrochemicals, but there is
      increasing interest in its fermentative production from renewable biomass.
      However, the current propionic acid fermentation process suffers from low product
      yield and productivity. In this work, the gene encoding phosphoenolpyruvate
      carboxylase (PPC) was cloned from Escherichia coli and expressed in
      Propionibacterium freudenreichii. PPC catalyzes the conversion of
      phosphoenolpyruvate to oxaloacetate with the fixation of one CO2. Its expression
      in P. freudenreichii showed profound effects on propionic acid fermentation.
      Compared to the wild type, the mutant expressing the ppc gene grew significantly
      faster, consumed more glycerol, and produced propionate to a higher final titer
      at a faster rate. The mutant also produced significantly more propionate from
      glucose under elevated CO2 partial pressure. These effects could be attributed to
      increased CO2 fixation and resulting changes in the flux distributions in the
      dicarboxylic acid pathway. 

PMID- 24878753
TI  - Optimization of expression of untagged and histidine-tagged human recombinant
      thrombin precursors in Escherichia coli.
AB  - The present study is focused on preparation of proper Escherichia coli expression
      system to ensure high yields of various modified precursors of human recombinant
      thrombin, a potential biopharmaceutical reagent. Two thrombin precursors, the
      smallest single-chain alpha-thrombin precursor prethrombin-2 and its shortened
      form prethrombin-2?13, and their His-tagged forms were used. In order to
      determine the effect of the different lengths and amino acid compositions of
      affinity His-tag on the target protein expression level, a variety of the His-tag
      sequences were used. We found out that the protein expression efficiency was
      closely related to the codons used for encoding of amino acids of fusion
      histidine tag. Optimization of culture medium composition is another way to
      increase yield of the target protein. Suitable medium composition can ensure cell
      growth to high densities which is related to total yield of expressed protein. In
      this study, a new optimized complex medium for batch fermentation was developed.
      Addition of nutrients like a yeast extract and enzymatic casein hydrolysate to
      the defined medium components had a positive impact on protein expression, where
      relatively high expression level of the target protein from total amount of
      cellular proteins was achieved. Further, we have focused on trace element
      solution composition, and the optimized nickel and selenium concentrations were
      determined. Our results show that the composition of essential trace metal
      solution has a major impact not only on expression level, but it can also affect
      cell growth rate.

PMID- 24878756
TI  - Non-sarcomatous spindle cell morphology in conventional lung adenocarcinoma: a
      clinicopathological study.
AB  - Non-sarcomatous spindle cell foci (N-SSCF) without aggressive invasiveness, also
      called morule-like lesions, occur occasionally in conventional lung
      adenocarcinoma, but their characteristics remain poorly understood. We identified
      N-SSCF in 7 (4.0 %) of 173 lung adenocarcinomas and examined their
      clinicopathological features. The patients were six men and one woman with a mean
      age of 57.0 years (range, 43-76 years). All tumors were papillary-predominant
      adenocarcinomas, ranging in size from 1 to 4.5 cm (mean, 2.7 cm). N-SSCF occupied
      10-30 % of the tumors, and in all cases, there were focal or multifocal
      transitions between the two morphotypes. Most N-SSCF were plug-like nodules
      filling the spaces of cancerous alveoli/tubules or patchy insular nests. N-SSCF
      frequently contained mucin + lumina and were positive for cytokeratin 7, thyroid
      transcription factor 1, and Napsin A, but negative for cytokeratin 5/6 and
      vimentin, similar to the adenocarcinoma cells of the same tumor. Five cases (71
      %) were at stage I or II, suggesting that N-SSCF can occur in an early phase of
      lung cancer. In an age-, sex-, and stage-matched control study, N-SSCF were not
      associated with prognosis (P = 0.471). We consider tumors with N-SSCF a distinct
      structural variant of adenocarcinoma without prognostic significance. They should
      be distinguished from true sarcomatous spindle cells and micropapillary
      components, which are associated with aggressive behavior.

PMID- 24878755
TI  - Molecular classification of breast cancer.
AB  - Breast cancer is a complex, multifaceted disease encompassing a great variety of
      entities that show considerable variation in clinical, morphological and
      molecular attributes. Traditional classifications including histological
      assessment and clinical staging are used to guide patient management. In recent
      years, there has been exponential progress in molecular analysis with profound
      implications for our understanding of breast cancer biology and, hence,
      classification. There are now genome-based frameworks for the molecular
      categorisation of breast cancer including the development of prognostic and
      predictive signatures that potentially allow individualisation of treatment. Here
      we review the current state of the molecular classifications of in situ and
      invasive breast cancer including special subtypes. Future perspectives are also
      provided. 

PMID- 24878758
TI  - Circadian variation of growth factor levels in platelet-rich plasma.
AB  - OBJECTIVE: The influence of circadian rhythms has recently been considered in
      advanced studies of chronopharmacology and chronotherapeutics. Although emerging
      studies have reported the usefulness of platelet-rich plasma (PRP), no reports
      have described the diurnal variations in PRP growth factor levels. In the present
      study, we hypothesized that growth factor levels in PRP show a significant
      diurnal variation. DESIGN: Controlled laboratory study. SETTING: Institutional.
      PARTICIPANTS: Ten adult male volunteers (mean age, 30.0 +/- 2.6 years; range, 26
      34 years). INTERVENTIONS: Each subject donated a 20-mL sample of fasting blood, 4
      times per day (7 AM, 11 AM, 3 PM, and 7 PM). MAIN OUTCOME MEASURES: Each blood
      sample was processed to produce PRP. Complete blood counts of peripheral blood
      (PB) and PRP, as well as quantitative determination of PRP growth factor levels
      (platelet-derived growth factor and transforming growth factor) were performed.
      Statistical analyses were conducted using a one-way repeated measures analysis of
      variance. RESULTS: No significant differences were observed in platelet, white
      blood cell, and red blood cell counts in the PB or in the PRP samples throughout
      the course of the day. In addition, there were no significant differences in PRP
      growth factor levels at the various time points. CONCLUSIONS: Significant diurnal
      variations in platelet counts and growth factor levels were not observed in PRP.
      Therefore, adjustments for diurnal variation in chronotherapy may not be
      important when PRP is used in clinical practice.

PMID- 24878757
TI  - Clinicopathological characteristics and outcome of nested carcinoma of the
      urinary bladder.
AB  - We present the clinicopathological features of 56 cases of the nested variant of
      urothelial bladder carcinoma. This is an uncommon variant of bladder cancer,
      recognized by the current WHO classification of urologic tumors. The nested
      component represented 100 % of the tumor in 24 cases. The architectural pattern
      of the tumor varied from solid expansile to infiltrative nests characterized by
      deceptively bland histologic features resembling von Brunn nests. Typical
      features of high-grade conventional urothelial carcinoma were present in 32
      cases. Most neoplastic cells had nuclei of low to intermediate nuclear grade with
      occasional nuclear enlargement, most frequently seen in deep areas of tumor. The
      nested component expressed cytokeratins 7, 20, CAM5.2, and high molecular weight
      (34betaE12), p63, Ki67, p53, p27, and GATA3. Tumor extension was T1 (n = 9),
      minimally T2 (n = 10), T2a (n = 1), T2b (n = 4), T3a (n = 8), T3b (n = 13), and
      T4a (n = 11). On follow-up, 36 of patients died of or were alive with disease
      from 2 to 80 months (mean 21 months). Four patients died of other causes. Eleven
      other patients remained disease free. Univariate survival analysis showed no
      differences for nested carcinoma compared with conventional urothelial carcinoma.
      As in conventional urothelial carcinoma, in nested carcinoma of the bladder pT
      category defined different survival groups. In summary, nested variant of
      urothelial bladder carcinoma is typically associated with advanced stage. In
      samples of limited volume, it may be misdiagnosed as proliferation of von Brunn
      nests or other nested-like bladder lesions, delaying definitive therapy.

PMID- 24878759
TI  - Cardiac arrest in a 21-year-old man after ingestion of 1,3-DMAA-containing
      workout supplement.
AB  - Dietary supplements containing 1,3-dimethylamylamine (DMAA) have been determined
      to be illegal by the Food and Drug Administration (FDA); although banned, the
      products are still widely available for purchase. Adverse effects reported
      include cardiac arrest, hemorrhagic stroke, and death. Nonetheless, such products
      remain popular among young people because of advertised claims of exercise
      performance enhancement and fat burning. We describe a case of a young man who
      took such a supplement and suffered a cardiac arrest. Notably, the product
      consumed was not on the FDA list of substances containing DMAA. This case
      highlights the importance for clinicians to be aware of the potential harm of the
      DMAA-containing products by maintaining a high index of suspicion in otherwise
      healthy individuals presenting with cardiac arrest. It is of particular
      importance to sports medicine physicians who are most involved in education and
      counseling of patients potentially at risk of taking such products.

PMID- 24878760
TI  - The effect of tuning cold plasma composition on glioblastoma cell viability.
AB  - Previous research in cold atmospheric plasma (CAP) and cancer cell interaction
      has repeatedly proven that the cold plasma induced cell death. It is postulated
      that the reactive oxygen species (ROS) and reactive nitrogen species (RNS) play a
      major role in the CAP cancer therapy. In this paper, we seek to determine a
      mechanism of CAP therapy on glioblastoma cells (U87) through an understanding of
      the composition of the plasma, including treatment time, voltage, flow-rate and
      plasma-gas composition. In order to determine the threshold of plasma treatment
      on U87, normal human astrocytes (E6/E7) were used as the comparison cell line.
      Our data showed that the 30 sec plasma treatment caused 3-fold cell death in the
      U87 cells compared to the E6/E7 cells. All the other compositions of cold plasma
      were performed based on this result: plasma treatment time was maintained at 30 s
      per well while other plasma characteristics such as voltage, flow rate of source
      gas, and composition of source gas were changed one at a time to vary the
      intensity of the reactive species composition in the plasma jet, which may
      finally have various effect on cells reflected by cell viability. We defined a
      term "plasma dosage" to summarize the relationship of all the characteristics and
      cell viability. 

PMID- 24878761
TI  - Function and regulation of the mono-ADP-ribosyltransferase ARTD10.
AB  - The transfer of ADP-ribose from NAD(+) to a substrate by ADP-ribosyltransferases,
      ADP-ribosylation, is a multifunctional posttranslational modification. While many
      studies have addressed the function of poly-ADP-ribosylation, for example, in DNA
      repair, signaling, and gene transcription, little is known about the role of mono
      ADP-ribosylation. Recent work describing the mono-ADP-ribosyltransferase
      ARTD10/PARP10 suggests that this enzyme affects apoptosis, NF-kappaB signaling,
      and DNA damage repair, at least in part dependent on its activity as mono-ADP
      ribosyltransferase. Moreover, the macrodomain-containing proteins MacroD1,
      MacroD2, and TARG1/C6orf130 were recently described as hydrolases, which remove
      mono-ADP-ribosylation thus providing evidence that this modification is
      reversible. In this review, we discuss these novel findings and their broader
      implications for cell behavior. We suggest functions of ARTD10 in immunity,
      metabolism, and cancer biology. 

PMID- 24878762
TI  - Constitutive hippocampal cholesterol loss underlies poor cognition in old
      rodents.
AB  - Cognitive decline is one of the many characteristics of aging. Reduced long-term
      potentiation (LTP) and long-term depression (LTD) are thought to be responsible
      for this decline, although the precise mechanisms underlying LTP and LTD
      dampening in the old remain unclear. We previously showed that aging is
      accompanied by the loss of cholesterol from the hippocampus, which leads to
      PI3K/Akt phosphorylation. Given that Akt de-phosphorylation is required for
      glutamate receptor internalization and LTD, we hypothesized that the decrease in
      cholesterol in neuronal membranes may contribute to the deficits in LTD typical
      of aging. Here, we show that cholesterol loss triggers p-Akt accumulation, which
      in turn perturbs the normal cellular and molecular responses induced by LTD, such
      as impaired AMPA receptor internalization and its reduced lateral diffusion.
      Electrophysiology recordings in brain slices of old mice and in anesthetized
      elderly rats demonstrate that the reduced hippocampal LTD associated with age can
      be rescued by cholesterol perfusion. Accordingly, cholesterol replenishment in
      aging animals improves hippocampal-dependent learning and memory in the water
      maze test. 

PMID- 24878763
TI  - Facial trustworthiness judgments in children with ASD are modulated by happy and
      angry emotional cues.
AB  - Appearance-based trustworthiness inferences may reflect the misinterpretation of
      emotional expression cues. Children and adults typically perceive faces that look
      happy to be relatively trustworthy and those that look angry to be relatively
      untrustworthy. Given reports of atypical expression perception in children with
      Autism Spectrum Disorder (ASD), the current study aimed to determine whether the
      modulation of trustworthiness judgments by emotional expression cues in children
      with ASD is also atypical. Cognitively-able children with and without ASD, aged 6
      12 years, rated the trustworthiness of faces showing happy, angry and neutral
      expressions. Trust judgments in children with ASD were significantly modulated by
      overt happy and angry expressions, like those of typically-developing children.
      Furthermore, subtle emotion cues in neutral faces also influenced trust ratings
      of the children in both groups. These findings support a powerful influence of
      emotion cues on perceived trustworthiness, which even extends to children with
      social cognitive impairments. 

PMID- 24878764
TI  - Neurosurgery at Medical College of Georgia, Georgia Regents University in Augusta
      (1956-2013).
AB  - : The neurosurgery service at the Medical College of Georgia, Georgia Regents
      University at Augusta has a rich history spanning almost 6 decades. Here, we
      review the development of neurological surgery as a specialty in Augusta and the
      history of the Department of Neurosurgery at Georgia Regents University. This
      article describes some of the early neurosurgeons in the city and those who have
      contributed to the field and helped to shape the department. Our functional and
      stereotactic program is emphasized. Our surgical epilepsy program dates back more
      than a half-century and remains a highly experienced program. We also describe
      our affiliation with the medical illustration graduate program, which was the
      first to be accredited and remains 1 of 4 such programs in the world. Finally, we
      list our alumni, former faculty, and current faculty, as well as the major
      accomplishments in our first decade as a full department.

PMID- 24878766
TI  - GDNF is involved in the barrier-inducing effect of enteric glial cells on
      intestinal epithelial cells under acute ischemia reperfusion stimulation.
AB  - Acute intestinal ischemia reperfusion (IR) injury is often associated with
      intestinal epithelial barrier (IEB) dysfunction. Enteric glial cells (EGCs) play
      an essential role in maintaining the integrity of IEB functions. However, the
      precise mechanism of EGCs under IR stimulation remains unclear. Here, we report
      that EGCs are closely involved in the modulation of IEB functions in response to
      IR challenge. The intestinal IR treatment led to the significant upregulation of
      the EGC activation marker, glial fibrillary acidic protein, accompanied by the
      increasing abundance of glial-derived neurotrophic factor (GDNF) and inducible
      nitric oxidase (iNOS) proteins, which was also confirmed in in vitro hypoxia
      reoxygenation (HR) tests. Co-culturing with EGCs attenuated the tight junctional
      abnormalities, blocked the downregulation of ZO-1 and occludin protein
      expression, and relieved the decrease of permeability of intestinal epithelial
      cell (IEC) monolayers under HR treatment. Furthermore, exogenous GDNF
      administration displays the barrier-protective effects similar to EGCs against HR
      stimulation, while RNA interference-mediated knockdown of GDNF significantly
      inhibited the protective capability of EGCs. The expression of both GDNF and iNOS
      proteins of EGCs was significantly upregulated by co-culturing with IECs, which
      was further increased by HR treatment. Interestingly, through inhibiting iNOS
      activity, the barrier-protective effect of EGCs was influenced in normal
      condition but enhanced in HR condition. These results suggest that GDNF plays an
      important role in the barrier-protective mechanism of activated EGCs under IR
      stimulation, whereas EGCs (via iNOS release) are also involved in intestinal
      inflammation response, which may contribute to IEB damage induced by IR injury. 

PMID- 24878767
TI  - ABCA7 in Alzheimer's Disease.
AB  - ATP-binding cassette A7 (ABCA7) gene has recently been identified as a strong
      genetic locus associated with late-onset Alzheimer's disease (LOAD) through
      genome-wide association studies (GWASs). ABCA7 is a member of the ATP-binding
      cassette (ABC) transporter gene superfamily, which codes for 49 ABC proteins,
      divided into 7 subfamilies (coded A-G). As a multispan transmembrane protein,
      ABCA7 is most abundantly expressed in the microglial cells in the brain. The
      levels of ABCA7 have been detected to be increased in the Alzheimer's disease
      (AD) brain, which positively correlated with amyloid plaque burden and disease
      severity. Emerging data suggests that ABCA7 could be associated with AD via
      various pathways, possibly including amyloid-beta (Abeta) accumulation, lipid
      metabolism, and phagocytosis. In this review, we summarize the known functions of
      ABCA7 and discuss the single-nucleotide polymorphisms (SNPs) related to LOAD, as
      well as their potential physiological effects. Finally, given the contributions
      of ABCA7 to AD pathogenesis, targeting ABCA7 might provide novel opportunities
      for AD therapy. 

PMID- 24878768
TI  - An Updated Analysis with 85,939 Samples Confirms the Association Between CR1
      rs6656401 Polymorphism and Alzheimer's Disease.
AB  - The complement receptor 1 (CR1) rs6656401 polymorphism was first identified to be
      associated with Alzheimer's disease (AD) in European ancestry. However, the
      following studies reported weak or no significant association in Chinese,
      Japanese, Korean, African-American, Polish, and Canadian populations. We think
      that these negative results may have been caused by either relatively small
      sample sizes compared with those used for the previous genome-wide association
      studies (GWAS) in European ancestry or the genetic heterogeneity of the rs6656401
      polymorphism in different populations. Here, we reevaluated this association
      using the relatively large-scale samples from previous 24 studies (N = 85,939,
      30,100 cases and 55,839 controls) by searching the PubMed, AlzGene, and Google
      Scholar databases. Using additive model, we did not identify significant
      heterogeneity among the 24 studies. We observed significant association between
      the rs6656401 polymorphism and AD in pooled populations (P = 1.82E-26, odds ratio
      (OR) = 1.18, 95 % confidence interval (CI) 1.15-1.22). In subgroup analysis, we
      identified significant results in East Asian population with P = 5.00E-04, OR =
      1.31, 95 % CI 1.13-1.52. To our knowledge, this is the first meta-analysis to
      investigate the association between rs6656401 polymorphism and AD in East Asian,
      African-American, Canadian, and European populations. Our analysis further
      supports previous findings that the CR1 rs6656401 polymorphism contributes to AD
      susceptibility. We believe that our findings will be very useful for future
      genetic studies on AD. 

PMID- 24878765
TI  - Genetic Addiction Risk Score (GARS): molecular neurogenetic evidence for
      predisposition to Reward Deficiency Syndrome (RDS).
AB  - We have published extensively on the neurogenetics of brain reward systems with
      reference to the genes related to dopaminergic function in particular. In 1996,
      we coined "Reward Deficiency Syndrome" (RDS), to portray behaviors found to have
      gene-based association with hypodopaminergic function. RDS as a useful concept
      has been embraced in many subsequent studies, to increase our understanding of
      Substance Use Disorder (SUD), addictions, and other obsessive, compulsive, and
      impulsive behaviors. Interestingly, albeit others, in one published study, we
      were able to describe lifetime RDS behaviors in a recovering addict (17 years
      sober) blindly by assessing resultant Genetic Addiction Risk Score (GARSTM) data
      only. We hypothesize that genetic testing at an early age may be an effective
      preventive strategy to reduce or eliminate pathological substance and behavioral
      seeking activity. Here, we consider a select number of genes, their
      polymorphisms, and associated risks for RDS whereby, utilizing GWAS, there is
      evidence for convergence to reward candidate genes. The evidence presented serves
      as a plausible brain-print providing relevant genetic information that will
      reinforce targeted therapies, to improve recovery and prevent relapse on an
      individualized basis. The primary driver of RDS is a hypodopaminergic trait
      (genes) as well as epigenetic states (methylation and deacetylation on chromatin
      structure). We now have entered a new era in addiction medicine that embraces the
      neuroscience of addiction and RDS as a pathological condition in brain reward
      circuitry that calls for appropriate evidence-based therapy and early genetic
      diagnosis and that requires further intensive investigation. 

PMID- 24878769
TI  - Sildenafil treatment in established right ventricular dysfunction improves
      diastolic function and attenuates interstitial fibrosis independent from
      afterload.
AB  - Right ventricular (RV) function is an important determinant of prognosis in
      congenital heart diseases, pulmonary hypertension, and heart failure. Preventive
      sildenafil treatment has been shown to enhance systolic RV function and improve
      exercise capacity in a model of fixed RV pressure load. However, it is unknown
      whether sildenafil has beneficial effects when treatment is started in
      established RV dysfunction, which is clinically more relevant. Our aim was to
      assess the effects of sildenafil treatment on RV function and fibrosis in a model
      of established RV dysfunction due to fixed afterload. Rats were subjected to
      pulmonary artery banding (PAB), which induced RV dysfunction after 4 wk,
      characterized by reduced exercise capacity, decreased tricuspid annular plane
      systolic excursion, and RV dilatation. From week 4 onward, 50% of rats were
      treated with sildenafil (100 mg.kg(-1).day(-1), n = 9; PAB-SIL group) or vehicle
      (n = 9; PAB-VEH group). At 8 wk, exercise capacity was assessed using cage
      wheels, and RV function was assessed using invasive RV pressure-volume
      measurements under anesthesia. Sildenafil treatment, compared with vehicle,
      improved RV ejection fraction (44 +/- 2% vs. 34 +/- 2%, P < 0.05, PAB-SIL vs. PAB
      VEH groups), reduced RV end-diastolic pressure (2.3 +/- 0.5 vs. 5.1 +/- 0.9 mmHg,
      P < 0.05), and RV dilatation (end-systolic volume: 468 +/- 45 vs. 643 +/- 71 MUl,
      P = 0.05). Sildenafil treatment also attenuated RV fibrosis (30 +/- 6 vs. 17 +/-
      30/00, P < 0.05) but did not affect end-systolic elastance, exercise capacity, or
      PKG or PKA activity. In conclusion, sildenafil improves RV diastolic function and
      attenuates interstitial fibrosis in rats with established RV dysfunction,
      independent from afterload. These results indicate that sildenafil treatment has
      therapeutic potential for established RV dysfunction. 

PMID- 24878771
TI  - Sex differences in myosin heavy chain isoforms of human failing and nonfailing
      atria.
AB  - Mammalian hearts express two myosin heavy chain (MHC) isoforms, which drive
      contractions with different kinetics and power-generating ability. The expression
      of the isoform that is associated with more rapid contraction kinetics and
      greater power output, MHC-alpha, is downregulated, with a concurrent increase in
      the relative amount of the slower isoform, MHC-beta, during the progression to
      experimentally induced or disease-related heart failure. This change in protein
      expression has been well studied in right and left ventricles in heart failure
      models and in humans with failure. Relatively little quantitative data exists
      regarding MHC isoform expression shifts in human failing atria. We previously
      reported significant increases in the relative amount of MHC-beta in the human
      failing left atrium. The results of that study suggested that there might be a
      sex-related difference in the level of MHC-beta in the left atrium, but the
      number of female subjects was insufficient for statistical analysis. The
      objective of this study was to test whether there is, in fact, a sex-related
      difference in the level of MHC-beta in the right and left atria of humans with
      cardiomyopathy. The results indicate that significant differences exist in atrial
      MHC isoform expression between men and women who are in failure. The results also
      revealed an unexpected twofold greater amount of MHC-beta in the nonfailing left
      atrium of women, compared with men. The observed sex-related differences in MHC
      isoform expression could impact ventricular diastolic filling during normal daily
      activities, as well as during physiologically stressful events. 

PMID- 24878770
TI  - Blunted cerebral blood flow velocity in response to a nitric oxide donor in
      postural tachycardia syndrome.
AB  - Cognitive deficits are characteristic of postural tachycardia syndrome (POTS).
      Intact nitrergic nitric oxide (NO) is important to cerebral blood flow (CBF)
      regulation, neurovascular coupling, and cognitive efficacy. POTS patients often
      experience defective NO-mediated vasodilation caused by oxidative stress. We have
      previously shown dilation of the middle cerebral artery in response to a bolus
      administration of the NO donor sodium nitroprusside (SNP) in healthy volunteers.
      In the present study, we hypothesized a blunted middle cerebral artery response
      to SNP in POTS. We used combined transcranial Doppler-ultrasound to measure CBF
      velocity and near-infrared spectroscopy to measure cerebral hemoglobin
      oxygenation while subjects were in the supine position. The responses of 17 POTS
      patients were compared with 12 healthy control subjects (age: 14-28 yr). CBF
      velocity in POTS patients and control subjects were not different at baseline (75
      +/- 3 vs. 71 +/- 2 cm/s, P = 0.31) and decreased to a lesser degree with SNP in
      POTS patients (to 71 +/- 3 vs. 62 +/- 2 cm/s, P = 0.02). Changes in total and
      oxygenated hemoglobin (8.83 +/- 0.45 and 8.13 +/- 0.48 MUmol/kg tissue) were
      markedly reduced in POTS patients compared with control subjects (14.2 +/- 1.4
      and 13.6 +/- 1.6 MUmol/kg tissue), primarily due to increased venous efflux. The
      data indicate reduced cerebral oxygenation, blunting of cerebral arterial
      vasodilation, and heightened cerebral venodilation. We conclude, based on the
      present study outcomes, that decreased bioavailability of NO is apparent in the
      vascular beds, resulting in a downregulation of NO receptor sites, ultimately
      leading to blunted responses to exogenous NO. 

PMID- 24878772
TI  - Exercise capacity is associated with endothelin-1 release during emotional
      excitement in coronary artery disease patients.
AB  - Endothelin-1 (ET-1), a potent vasoconstrictor, IL-6, and catecholamines are
      increased and heart rate variability [SD of normal to normal R-R intervals
      (SDNN)] decreased during emotional excitement, but individual responses vary. We
      tested the hypothesis that exercise capacity is associated with physiological
      responses caused by real-life emotional excitement. We measured the plasma levels
      of ET-1, IL-6, catecholamines, heart rate, and SDNN in enthusiastic male ice
      hockey spectators (n = 51; age, 59 +/- 9 years) with stable coronary artery
      disease (CAD) at baseline and during the Finnish National Ice Hockey League's
      final play-off matches. Maximal exercise capacity (METs) by bicycle exercise test
      and left ventricular ejection fraction (LVEF) were measured on a separate day. ET
      1 response from baseline to emotional excitement correlated with maximal METs (r
      = -0.30; P = 0.040). In a linear stepwise regression analysis age, body mass
      index (BMI), METs, LVEF, basal ET-1, and subjective experience of excitement were
      entered the model as independent variables to explain ET-1 response. This model
      explained 27% of ET-1 response (P = 0.003). Maximal METs were most strongly
      correlated with ET-1 response (beta = -0.45; partial correlation r = -0.43; P =
      0.002), followed by BMI (beta = -0.31; partial correlation r = -0.31; P = 0.033)
      and LVEF (beta = -0.30; partial correlation r = -0.33; P = 0.023). Exercise
      capacity may protect against further cardiovascular events in CAD patients,
      because it is associated with reduced ET-1 release during emotional excitement. 

PMID- 24878773
TI  - Vasoconstrictor role of cyclooxygenase-1-mediated prostacyclin synthesis in non
      insulin-dependent diabetic mice induced by high-fat diet and streptozotocin.
AB  - This study tested the hypothesis that in diabetic arteries, cyclooxygenase (COX)
      1 mediates endothelial prostacyclin (PGI2) synthesis, which evokes
      vasoconstrictor activity under the pathological condition. Non-insulin-dependent
      diabetes was induced to C57BL/6 mice and those with COX-1 deficiency (COX-1(-/-)
      mice) using a high-fat diet in combination with streptozotocin injection. In
      vitro analyses were performed 3 mo after. Results showed that in diabetic aortas,
      the endothelial muscarinic receptor agonist ACh evoked an endothelium-dependent
      production of the PGI2 metabolite 6-keto-PGF1alpha, which was abolished in COX-1(
      /-) mice. Meanwhile, COX-1 deficiency or COX-1 inhibition prevented
      vasoconstrictor activity in diabetic abdominal aortas, resulting in enhanced
      relaxation evoked by ACh. In a similar manner, COX-1 deficiency increased the
      relaxation evoked by ACh in nitric oxide synthase-inhibited diabetic renal
      arteries. Also, in diabetic abdominal aortas and/or renal arteries, both PGI2 and
      the COX substrate arachidonic acid evoked contractions similar to those of
      nondiabetic mice. However, the contraction to arachidonic acid, but not that to
      PGI2, was abolished in vessels from COX-1(-/-) mice. Moreover, we found that 3 mo
      after streptozotocin injection, systemic blood pressure increased in diabetic
      C57BL/6 mice but not in diabetic COX-1(-/-) mice. These results explicitly
      demonstrate that in the given arteries from non-insulin-dependent diabetic mice,
      COX-1 remains a major contributor to the endothelial PGI2 synthesis that evokes
      vasoconstrictor activity under the pathological condition. Also, our data suggest
      that COX-1 deficiency prevents or attenuates diabetic hypertension in mice,
      although this could be related to the loss of COX-1-mediated activities derived
      from both vascular and nonvascular tissues. 

PMID- 24878774
TI  - Timing and magnitude of systolic stretch affect myofilament activation and
      mechanical work.
AB  - Dyssynchronous activation of the heart leads to abnormal regional systolic
      stretch. In vivo studies have suggested that the timing of systolic stretch can
      affect regional tension and external work development. In the present study, we
      measured the direct effects of systolic stretch timing on the magnitude of
      tension and external work development in isolated murine right ventricular
      papillary muscles. A servomotor was used to impose precisely timed stretches
      relative to electrical activation while a force transducer measured force output
      and strain was monitored using a charge-couple device camera and topical markers.
      Stretches taking place during peak intracellular Ca(2+) statistically increased
      peak tension up to 270%, whereas external work due to stretches in this interval
      reached values of 500 J/m. An experimental analysis showed that time-varying
      elastance overestimated peak tension by 100% for stretches occurring after peak
      isometric tension. The addition of the force-velocity relation explained some
      effects of stretches occurring before the peak of the Ca(2+) transient but had no
      effect in later stretches. An estimate of transient deactivation was measured by
      performing quick stretches to dissociate cross-bridges. The timing of transient
      deactivation explained the remaining differences between the model and
      experiment. These results suggest that stretch near the start of cardiac tension
      development substantially increases twitch tension and mechanical work
      production, whereas late stretches decrease external work. While the increased
      work can mostly be explained by the time-varying elastance of cardiac muscle, the
      decreased work in muscles stretched after the peak of the Ca(2+) transient is
      largely due to myofilament deactivation. 

PMID- 24878775
TI  - Wave potential and the one-dimensional windkessel as a wave-based paradigm of
      diastolic arterial hemodynamics.
AB  - Controversy exists about whether one-dimensional wave theory can explain the
      "self-canceling" waves that accompany the diastolic pressure decay and discharge
      of the arterial reservoir. Although it has been proposed that reservoir and wave
      effects be treated as separate phenomena, thus avoiding the issue of self
      canceling waves, we have argued that reservoir effects are a phenomenological and
      mathematical subset of wave effects. However, a complete wave-based explanation
      of self-canceling diastolic expansion (pressure-decreasing) waves has not yet
      been advanced. These waves are present in the forward and backward components of
      arterial pressure and flow (P +/- and Q +/-, respectively), which are calculated
      by integrating incremental pressure and flow changes (dP +/- and dQ +/-,
      respectively). While the integration constants for this calculation have
      previously been considered arbitrary, we showed that physiologically meaningful
      constants can be obtained by identifying "undisturbed pressure" as mean
      circulatory pressure. Using a series of numeric experiments, absolute P +/- and Q
      +/- values were shown to represent "wave potential," gradients of which produce
      propagating wavefronts. With the aid of a "one-dimensional windkessel," we showed
      how wave theory predicts discharge of the arterial reservoir. Simulated data,
      along with hemodynamic recordings in seven sheep, suggested that self-canceling
      diastolic waves arise from repeated and diffuse reflection of the late systolic
      forward expansion wave throughout the arterial system and at the closed aortic
      valve, along with progressive leakage of wave potential from the conduit
      arteries. The combination of wave and wave potential concepts leads to a
      comprehensive one-dimensional (i.e., wave-based) explanation of arterial
      hemodynamics, including the diastolic pressure decay.

PMID- 24878776
TI  - Impact of neoadjuvant chemotherapy on immediate breast reconstruction: a meta
      analysis.
AB  - OBJECTIVE: The objective of this study was to perform a meta-analysis of
      published studies for evaluating the impact of neoadjuvant chemotherapy (NAC) on
      immediate breast reconstruction. METHODS: We searched medical databases to
      identify appropriate studies that assessed the impact of NAC on immediate breast
      reconstruction from the inception of this technique through April 2013. We then
      performed a meta-analysis of these studies. RESULTS: Our searches identified 11
      studies among 1,840 citations. In the meta-analysis, NAC did not increase the
      overall rate of complications after immediate breast reconstruction (odds ratio
      [OR] = 0.59; 95% confidence interval[CI] = 0.38-0.91). The complication rate was
      also unaffected by NAC when we considered infections (OR = 0.82; 95% CI = 0.46
      1.45), hematomas (OR = 1.35; 95% CI = 0.57-3.21), and seromas (OR = 0.77; 95% CI
      = 0.23-2.55). Additionally, expander or implant loss did not significantly
      increase in patients after NAC (OR = 1.59; 95% CI = 0.91-2.79). Only 2 studies
      (202 procedures) had reported total autologous flap loss, and they were included
      in our analysis; both studies found no association between NAC and total flap
      loss. CONCLUSION: Our analysis suggests that NAC does not increase the
      complication rate after immediate breast reconstruction. For appropriately
      selected patients, immediate breast reconstruction following NAC is a safe
      procedure. The best way to study this issue in the future is to conduct a
      multicenter prospective study with a longer follow-up period and more clearly
      defined parameters.

PMID- 24878778
TI  - Cyclometalated Pd(II) and Ir(III) 2-(4-bromophenyl)pyridine complexes with N
      heterocyclic carbenes (NHCs) and acetylacetonate (acac): synthesis, structures,
      luminescent properties and application in one-pot oxidation/Suzuki coupling of
      aryl chlorides containing hydroxymethyl.
AB  - A series of cyclopalladated 2-(4-bromophenyl)pyridine (bpp) complexes
      [Pd(bpp)(NHC)Cl] 1-3, [Pd(bpp)(acac)] 4, cyclometalated iridium(iii) complexes
      [Ir(bpp)2Cl]25 and [Ir(bpp)2(acac)] 6 have been synthesized and characterized.
      Their detailed structures have been determined by X-ray diffraction and many
      intermolecular C-HX (Cl, Br, pi) and pipi interactions were found in their
      crystals. Cyclometalated complexes 1-4 and 6 exhibit luminescence with emission
      peaks of 390-543 nm in dichloromethane solution under UV irradiation. Their
      application to coupling reactions of aryl chlorides containing hydroxymethyl was
      also investigated. An efficient 3/Cu cocatalyzed oxidation/Suzuki reaction for
      the synthesis of biarylaldehydes from chloro-phenylmethanol and arylboronic acids
      in air has been developed. In addition, a 6/3-cocatalyzed one-pot reaction of
      acetylferrocene, (2-amino-5-chlorophenyl)methanol, and arylboronic acids provided
      6-aryl-2-ferrocenylquinolines in moderate to good yields. 

PMID- 24878777
TI  - Searching for a toxic key to unlock the mystery of anemonefish and anemone
      symbiosis.
AB  - Twenty-six species of anemonefish of the genera Amphiprion and monospecific
      Premnas, use only 10 species of anemones as hosts in the wild (Families:
      Actiniidae, Stichodactylidae and Thalassianthidae). Of these 10 anemone species
      some are used by multiple species of anemonefish while others have only a single
      anemonefish symbiont. Past studies have explored the different patterns of usage
      between anemonefish species and anemone species; however the evolution of this
      relationship remains unknown and has been little studied over the past decade.
      Here we reopen the case, comparing the toxicity of crude venoms obtained from
      anemones that host anemonefish as a way to investigate why some anemone species
      are used as a host more than others. Specifically, for each anemone species we
      investigated acute toxicity using Artemia francisca (LC50), haemolytic toxicity
      using ovine erythrocytes (EC50) and neurotoxicity using shore crabs (Ozius
      truncatus). We found that haemolytic and neurotoxic activity varied among host
      anemone species. Generally anemone species that displayed greater haemolytic
      activity also displayed high neurotoxic activity and tend to be more toxic on
      average as indicated by acute lethality analysis. An overall venom toxicity
      ranking for each anemone species was compared with the number of anemonefish
      species that are known to associate with each anemone species in the wild.
      Interestingly, anemones with intermediate toxicity had the highest number of
      anemonefish associates, whereas anemones with either very low or very high
      toxicity had the fewest anemonefish associates. These data demonstrate that
      variation in toxicity among host anemone species may be important in the
      establishment and maintenance of anemonefish anemone symbiosis. 

PMID- 24878779
TI  - Specificity of cytochemical and fluorescence methods of senescence-associated
      beta-galactosidase detection for ageing driven by replication and time.
AB  - Senescence-associated beta-galactosidase (SA-beta-Gal) is a widely used marker of
      senescent cells in vitro and in vivo. In this report, young and senescent human
      peritoneal mesothelial cells (HPMCs) and fragments of the omentum, from which
      these cells were isolated, were subjected to simultaneous examination of SA-beta
      Gal using two methods, i.e. cytochemical and fluorescent methods. The results
      obtained were confronted with the cumulative number of population doublings (CPD)
      and the calendar age of the tissue donor. The study showed that senescence of
      HPMCs proceeds with either an increased percentage of SA-beta-Gal-positive cells
      or increased enzyme activity. Cytochemical SA-beta-Gal staining in early-passage
      cultures negatively correlated with CPD values but not with donor age in both
      cell cultures and omentum specimens. Conversely, SA-beta-Gal activity measured
      with the fluorescence method rose in proportion to the calendar age of the donor
      either in early-passage cultures or in primary cell isolates from omental tissue.
      At the same time it was not related to the CPD values. These findings may suggest
      that with respect to at least peritoneal mesothelial cells, the cytochemical and
      fluorescent methods of SA-beta-Gal detection, though complementary, are
      informative for different levels of aging, i.e. the cytochemical approach for
      senescence in vitro and the fluorescence-based technique for organismal aging in
      vivo. 

PMID- 24878780
TI  - Applying cybernetic technology to diagnose human pulmonary sounds.
AB  - Chest auscultation is a crucial and efficient method for diagnosing lung disease;
      however, it is a subjective process that relies on physician experience and the
      ability to differentiate between various sound patterns. Because the
      physiological signals composed of heart sounds and pulmonary sounds (PSs) are
      greater than 120 Hz and the human ear is not sensitive to low frequencies,
      successfully making diagnostic classifications is difficult. To solve this
      problem, we constructed various PS recognition systems for classifying six PS
      classes: vesicular breath sounds, bronchial breath sounds, tracheal breath
      sounds, crackles, wheezes, and stridor sounds. First, we used a piezoelectric
      microphone and data acquisition card to acquire PS signals and perform signal
      preprocessing. A wavelet transform was used for feature extraction, and the PS
      signals were decomposed into frequency subbands. Using a statistical method, we
      extracted 17 features that were used as the input vectors of a neural network. We
      proposed a 2-stage classifier combined with a back-propagation (BP) neural
      network and learning vector quantization (LVQ) neural network, which improves
      classification accuracy by using a haploid neural network. The receiver operating
      characteristic (ROC) curve verifies the high performance level of the neural
      network. To expand traditional auscultation methods, we constructed various PS
      diagnostic systems that can correctly classify the six common PSs. The proposed
      device overcomes the lack of human sensitivity to low-frequency sounds and
      various PS waves, characteristic values, and a spectral analysis charts are
      provided to elucidate the design of the human-machine interface. 

PMID- 24878781
TI  - Association of rs11190870 near LBX1 with adolescent idiopathic scoliosis in East
      Asians: a systematic review and meta-analysis.
AB  - BACKGROUND CONTEXT: The rs11190870 single nucleotide polymorphism in the 3'
      flanking region of the LBX1 gene has been implicated in the etiology of
      adolescent idiopathic scoliosis (AIS). A thorough appraisal of the evidence
      supporting this association has not been previously attempted. PURPOSE: To
      provide a comprehensive assessment and synthesis of the currently available
      evidence on the association between rs11190870 and AIS. STUDY DESIGN: A
      systematic review and meta-analysis. METHODS: This review followed the Preferred
      Reporting Items for Systematic Review and Meta-Analyses guidelines. PubMed
      (MEDLINE), EMBASE, Scopus, and HuGE Literature Finder databases were
      systematically searched through November 2013 to identify relevant studies
      following a sensitive strategy. Summary odds ratios (ORs) and corresponding 95%
      confidence intervals (CIs) were estimated using the fixed-effect inverse variance
      model for allelic (T vs. C) and genotypic comparisons. RESULTS: Meta-analysis of
      four studies conducted in East Asian populations (n=3,215 AIS cases and n=15,347
      controls) found a highly statistically significant and robust association between
      rs11190870 and AIS. Comparison of summary ORs indicated a codominant model effect
      of the T allele. Carriers of the TC and TT genotypes were 69% (OR=1.69, 95% CI:
      1.48-1.94, p<.001) and 162% (OR=2.62, 95% CI: 2.28-3.02, p<.001), respectively,
      more likely to have AIS compared with carriers of the CC genotype. CONCLUSIONS:
      Based on a comprehensive analysis of the currently available evidence, rs11190870
      is likely a susceptibility variant for AIS in East Asians. Further investigation
      of this association is necessary in other populations.

PMID- 24878783
TI  - Prof. Dr. Geraldo Gomes de Freitas.

PMID- 24878782
TI  - The UV filter benzophenone 3 (BP-3) activates hormonal genes mimicking the action
      of ecdysone and alters embryo development in the insect Chironomus riparius
      (Diptera).
AB  - Numerous studies have evaluated the endocrine effects of UV filters in
      vertebrates, but little attention has been paid to their possible hormonal
      activity in invertebrates. We examined the effects of benzophenone-3 (BP-3), one
      of the most common sunscreen agents, in Chironomus riparius (Insecta), a
      reference organism in aquatic toxicology. Salivary glands from larvae were
      treated with either the hormone ecdysone or BP-3 to compare the response of
      endocrine genes. It was found that BP-3 elicits the same effects as the natural
      hormone activating the expression of a set of ecdysone responsive genes. BP-3
      also activated the stress gene hsp70. Interestingly, similar effects have been
      confirmed in vivo in embryos. Moreover, BP-3 also altered embryogenesis delaying
      hatching. This is the first demonstration of hormonal activity of UV filters in
      invertebrates, showing a mode of action similar to ecdysteroid hormones. This
      finding highlights the potential endocrine disruptive effects of these emergent
      pollutants. 

PMID- 24878784
TI  - Shedding fluorescent light into the antinuclear antibody world.

PMID- 24878785
TI  - Comparison of low level laser, ultrasonic therapy and association in joint pain
      in Wistar rats.
AB  - INTRODUCTION: Both therapeutic ultrasound as a low level laser therapy are used
      to control musculoskeletal pain, despite controversy about its effects, yet the
      literature is poor and also presents conflicting results on possible cumulative
      effects of techniques association. The aim was to compare the antinociceptive
      effects of low level laser therapy, therapeutic ultrasound and the association.
      METHODS: 24 Wistar rats were divided into: GPL--induction of hyperesthesia in the
      right knee, and untreated; GUS--treated with therapeutic ultrasound (1 MHz, 0.4
      W/cm2) GL--low intensity laser (830 nm, 8 J/cm2); GL+US--treated with both
      techniques. To produce the hyperesthesia 100 MUl of 5% formalin solution were
      injected into the tibiofemoral joint space, which was assessed by von Frey
      filament digital before (EV1), 15 (EV2), 30 (EV3) and 60 (EV4) minutes after
      induction. RESULTS: In comparison within groups, for the withdrawal threshold
      when the fi lament was applied to the knee, the back to baseline was observed
      only for GUS. Comparisons between groups were not different in EV3, and GL was
      higher than GPL. In EV4 the three groups effectively treated were higher than
      placebo. On withdrawal threshold on the plantar surface, GL showed return to
      baseline values already in EV3, and GUS and GL+US returned in EV4. Comparing the
      groups in EV3 there was a significantly lower threshold to compare GPL with GL
      and GUS (p <0.05), and there was only EV4 differences when comparing GPL with
      GUS. CONCLUSION: Both modalities showed antinociceptive effects.

PMID- 24878786
TI  - Detection of anti-nuclear antibodies by indirect immunofluorescence on HEp-2
      cells: setting the appropriate screening dilution for the diagnosis of autoimmune
      rheumatic diseases.
AB  - OBJECTIVE: To establish the abnormal title and the appropriate screening dilution
      for ANA (antinuclear antibodies) test by indirect immunofluorescence on HEp-2
      cells (ANA HEp-2). METHODS: An analysis of ANA Hep-2 in serum samples from 126
      healthy individuals was performed. The samples were screened at a dilution of
      1:80, and those positive were diluted to the title of 1:5120. The abnormal title
      of ANA was defined as that corresponding to the 95th percentile of the test in
      this population. The sensitivity of the different titles of antinuclear
      antibodies was determined in a group of 136 patients with a diagnosis of
      autoimmune rheumatic disease, and the specificity was determined in a group of
      118 patients with other rheumatic diseases. The optimal cutoff value of the test
      was determined by ROC curve analysis. RESULTS: The frequency of ANA positivity in
      healthy subjects was 13.2%. There was no difference in the frequency of positive
      results according to gender or age. The abnormal title of ANA was defined as the
      dilution of 1:160. The 1:80 dilution had sensitivity of 87.7% and specificity of
      67.8%, while the 1:160 dilution had sensitivity of 82% and specificity of 73.7%.
      By ROC curve analysis, a dilution of 1:160 corresponded to the optimal cutoff
      value. CONCLUSION: The abnormal title and the optimal cutoff value of ANA HEp-2
      in the population was 1:160. Therefore, the dilution of 1:160 is the optimal
      screening dilution, with better specificity but without significantly
      compromising the sensitivity of the diagnostic test.

PMID- 24878787
TI  - Frequency of antiparvovirus B19 antibodies in rheumatoid arthritis and systemic
      lupus erythematosus.
AB  - OBJECTIVE: To determine the frequency of antiparvovirus B19 (B19) antibodies in
      patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE),
      and the possible correlation of anti-B19 seropositivity with disease activity and
      quality of life. PATIENTS AND METHODS: Serum samples from 57 patients with RA, 45
      with SLE and 65 healthy controls were used. We applied protocol with clinical
      data, and the Disease Activity Score 28 (DAS 28), Systemic Lupus Erythematosus
      Disease Activity Index (SLEDAI) and Health Assessment Questionnaire (HAQ)
      indexes. The anti-B19 serology was done by enzyme-linked immunosorbent assay
      (ELISA). RESULTS: The mean age of patients was 42.74 +/- 14.09 years, and of
      controls was 38.38 +/- 13.42 years. 79 patients had active disease (77.5%), and
      23 had inactive disease (22.5%). Anti-B19 (IgG) was positive in 49 (86.0%; CI 95%
      77.0-95.0) RA patients, 38 (84.4%; CI 95% 73.9-95.0) SLE patients, and 40 (61.5%;
      CI 95% 49.7-73.4) controls (p = 0.002). Anti-B19 (IgM) was positive in 3 (5.3%;
      CI 95% 0.0-11.1) RA patients, in 7 (15.6%; CI 95% 5.0-26,2) SLE patients, and in
      1 (1.5%; CI 95% 0.0-4.5) control (p = 0.011).There was no correlation of anti-B19
      reactivity with disease activity and with DAS 28, HAQ and SLEDAI indexes.
      CONCLUSION: This study demonstrated that the studied population is exposed to
      infection by B19, which demands attention with its manifestations, especially
      among patients at greatest risk, such as those immunosuppressed.

PMID- 24878788
TI  - Investigation of stress, anxiety and depression in women with fibromyalgia: a
      comparative study.
AB  - INTRODUCTION: Depression has emerged as the most prevalent mental disorder in
      patients with fibromyalgia. Stress, whose stages are alarm, resistance, near
      exhaustion and exhaustion, constitutes a physical reaction to a threatening
      situation. OBJECTIVE: To investigate the levels of stress, anxiety and depression
      in women with fibromyalgia, comparing them with those of healthy women. PATIENTS
      AND METHODS: Participants were 50 women, 25 with a diagnosis of fibromyalgia
      according to the criteria of the American College of Rheumatology, and 25 without
      this diagnosis, matched for age. Instruments used: Lipp Inventory of Stress
      Symptoms for Adults (LISS), State-Trait Anxiety Inventory (STAI) and Beck
      Depression Inventory (BDI). RESULTS: The mean age was 49.36 years for the group
      with fibromyalgia (FM) and 49.20 years for the group without fibromyalgia (non
      FM). FM showed a higher incidence of stress (96%) compared with non-FM (5%). The
      resistance phase was predominant in both groups, FM (42%) and non-FM (100%). In
      FM there was distribution of the four stages (alarm, resistance, near-exhaustion
      and exhaustion). The differences between phases in the analyzed groups were
      significant (p < 0.001). FM showed predominance of psychological symptoms (54%);
      non-FM did show the same frequency of psychological and physical/psychological
      (40%) symptoms. Symptoms of state and trait anxiety and of depression in FM were
      significantly higher, when compared with non-FM (p < 0.01). CONCLUSION: Stress
      index (96%), trait anxiety (over 50) and clinically relevant depression (greater
      than 20) in FM were relevant. The understanding of the emotional variables
      involved in fibromyalgia is important to define the therapeutic strategy.

PMID- 24878790
TI  - The contribution of HLA molecules to Dupuytren's contracture in a Southeast
      Brazilian population.
AB  - PURPOSE: The aim of the present study was to investigate the HLA phenotype in
      Dupuytren's contracture (DC) patients in order to verify the correlation of these
      alleles with risk factors for development of DC in the Brazilian population.
      METHODS: This was a case-controlled study of 25 DC patients and 443 healthy
      individuals with no history of HLA-associated diseases. HLA class I and class II
      typing was performed using the polymerase chain reaction sequence-specific primer
      method. RESULTS: The HLAB*18 phenotype was observed in 32% of the patients and
      10.5% of controls. However, P values did not remain significant after correction.
      DISCUSSION: Although we observed an increased tendency of DC patients to possess
      the HLA-B*18 allele, the results were not statistically significant after
      correction. This allele was higher in patients of Italian and/or Spanish
      ethnicity, localities with frequencies higher than 18.0% and 14.0% respectively.
      Further investigation with a larger cohort of DC patients is required to confirm
      the potential role of HLA in this disease.

PMID- 24878789
TI  - Profile of the use of disease modifying drugs in the Brazilian Registry of
      Spondyloarthritides.
AB  - INTRODUCTION: Few studies have evaluated the profile of use of disease modifying
      drugs (DMD) in Brazilian patients with spondyloarthritis (SpA). METHODS: A common
      research protocol was applied prospectively in 1505 patients classified as SpA by
      criteria of the European Spondyloarthropathies Study Group (ESSG), followed at 29
      referral centers in Rheumatology in Brazil. Demographic and clinical variables
      were obtained and evaluated, by analyzing their correlation with the use of DMDs
      methotrexate (MTX) and sulfasalazine (SSZ). RESULTS: At least one DMD was used by
      73.6% of patients: MTX by 29.2% and SSZ by 21.7%, while 22.7% used both drugs.
      The use of MTX was significantly associated with peripheral involvement, and SSZ
      was associated with axial involvement, and the two drugs were more administered,
      separately or in combination, in the mixed involvement (p < 0.001). The use of a
      DMD was significantly associated with Caucasian ethnicity (MTX , p = 0.014),
      inflammatory back pain (SSZ, p = 0.002) , buttock pain (SSZ, p = 0.030), neck
      pain (MTX, p = 0.042), arthritis of the lower limbs (MTX, p < 0.001), arthritis
      of the upper limbs (MTX, p < 0.001), enthesitis (p = 0.007), dactylitis (MTX, p <
      0.001), inflammatory bowel disease (SSZ, p < 0.001) and nail involvement (MTX, p
      < 0.001). CONCLUSION: The use of at least one DMD was reported by more than 70%
      of patients in a large cohort of Brazilian patients with SpA, with MTX use more
      associated with peripheral involvement and the use of SSZ more associated with
      axial involvement.

PMID- 24878792
TI  - Back schools in Brazil: a review of the intervention methodology, assessment
      tools, and results.
AB  - The Back School is characterized as an educational program aimed at individuals
      who have chronic pain in spine. In Brazil, a growing number of research studies
      on the effects of such programs have been observed in the last decades. Thus, the
      purpose of this systematic review was to identify studies on Back Schools carried
      out in Brazil with a population of adults and elderlies, and to compare their
      intervention methodologies, data collection tools, and results. A search for
      scientific articles and Master's and doctoral theses in several databases was
      conducted. The keywords used in that search were Postural Program; Postural
      School; Back School; Back Care Education; Back Education, as well as the
      respective terms in Portuguese. Eighteen studies were found, being fourteen
      quantitative and four qualitative studies.The studies showed many differences
      between them, in both the interventions proposed and the methodological design.
      However, the use of similar tools for assessing pain intensity, functional
      capacity, and quality of life between the quantitative studies allowed a partial
      comparison of the efficacy of those programs.The studies included in this
      systematic review demonstrated, in general, the immediate efficacy in reducing
      pain and improving functional capacity and quality of life after the Back School.
      Results, however, are still conflicting regarding the efficacy in the medium and
      long terms. Thus, it becomes necessary to conduct further studies that include
      follow-up assessments in the medium and long terms in order to obtain more
      accurate conclusions about the efficacy of Back Schools. 

PMID- 24878791
TI  - IV Brazilian guidelines for autoantibodies on HEp-2 cells.
AB  - OBJECTIVE: The Fourth Brazilian Consensus for Autoantibodies Screening in HEp-2
      Cells (ANA) was held in Vitoria, Espirito Santo, and aimed to discuss strategies
      and recommendations about the technique, standardization, interpretation and
      quality control of the indirect immunofluorescence reaction on HEp-2 cells.
      METHODS: Twenty three ANA experts from university centers and private
      laboratories in different areas from Brazil discussed and agreed upon
      recommendations for the fourth edition of the Brazilian Consensus for
      Autoantibodies Screening in HEp-2 Cells. RESULTS AND CONCLUSION: The 4th ANA
      Consensus included three novel patterns into the existing algorithm (cytoplasmic
      Rods and Rings, nuclear Quasi-homogeneous, and CENP-F). Emphasis was given to the
      need of attention in describing the peculiar mixed pattern elicited by anti-DNA
      topoisomerase I (Scl-70) autoantibodies, comprising nuclear fine specked,
      nucleolar homogeneous pattern, NOR staining in metaphase plates, and cytoplasmic
      fine speckled patterns. The group also emphasized the need for continuous quality
      control in indirect immunofluorescence assays, the establishment of screening
      dilutions, as well as conjugate titration. An alert was made regarding the
      heterogeneity of commercial kits in defining patterns and the use of solid phase
      methodologies to determine the presence of autoantibodies.

PMID- 24878793
TI  - ANCA associated vasculitis and chronic lymphocytic leukemia: a rare association.
AB  - The aim of the present work is to discuss the report of a patient who had
      simultaneous diagnosis of two rare diseases, vasculitis related to antineutrophil
      cytoplasmic antibodies and chronic lymphocytic leukemia. Both are diseases that
      may be multisystemic and thus cause diagnostic confusion. In this case, the
      patient had renal, pulmonary, hematological, and ocular symptoms, which could be
      secondary to vasculitis both as to leukemia. With the aid of imaging studies,
      pathological studies, immunohistochemistry and immunophenotyping, we conclude
      that it was a combination of the two diseases. There are other reports in
      literature of this association, however, with pANCA positive, this is the first
      report of chronic lymphocytic leukemia associated with cANCA positive vasculitis.

PMID- 24878794
TI  - Hemochromatosis simulating rheumatoid arthritis: a case report.
AB  - This is a report of a patient who had a previous diagnosis of rheumatoid
      arthritis, nonerosive, rheumatoid factor negative, that despite the therapeutic
      approach presented progressive worsening of the articular and general condition.
      After extensive research, she had a diagnosis of hemochromatosis. Joint symptoms
      are common manifestations in hemochromatosis. The arthropathy of hemochromatosis
      may resemble inflammatory arthropathy mimicking RA, particularly in the most
      common sites as 2nd and 3rd metacarpophalangeal. Radiologically are observed
      decreased joint space, subchondral sclerosis, cyst formation and
      chondrocalcinosis. Treatment with disease modifying drugs for rheumatoid
      arthritis tend to worsen the clinical picture, since the liver is the major site
      of deposition of iron in hemochromatosis and these medications are known to be
      hepatotoxic. Phlebotomy treatment for hemochromatosis is apparently ineffective
      in reversing the articular manifestations, which requires the association with
      iron chelating drugs. Due to the apparent difficulty in differentiating between
      the two diseases, a screening profile of iron in patients with rheumatoid
      arthritis with atypical progression is necessary. 

PMID- 24878795
TI  - "Milk of calcium": a rare presentation of calcinosis.
AB  - Rheumatic diseases such as juvenile dermatomyositis (JDM), juvenile sistemic
      lupus erythematosus (JSLE) and sistemic sclerosis may have calcium deposits in
      the subcutaneous and muscle tissues known as calcinosis. Extensive calcium-laden
      fluid collections referred as "milk of calcium" are rare forms of calcinosis in
      JDM. We describe a 15-year old patient with overlap syndrome
      (sclerodermatomyositis and JSLE), whose magnetic resonance imaging (MRI) showed
      perimusculares fluid collections in the lower limbs. During surgery, we observed
      the presence of whitish fluid collection suggestive of "milk of calcium". 

PMID- 24878796
TI  - Nutritional profile in rheumatoid arthritis.
AB  - BACKGROUND: Atherosclerosis in Rheumatoid Arthritis (RA) patients may be
      aggravated by obesity. OBJECTIVE: To study the nutritional status of patients
      with RA. METHODS: Observational cross sectional study of 102 RA. Patients were
      studied for clinical, demographic, serologic, activity and nutritional profile.
      In the latter we included: measurement of body mass index (BMI), waist-hip ratio;
      bicipital skinfold (BSF) and their adequacy; triceps skinfold measure (TSF) and
      its adequacy and arm muscle circumference (AMC) and its adequacy. Association
      studies of nominal data were done using Fisher and chi-square tests and the Mann
      Whitney and unpaired Student t tests for numerical data. For correlation
      calculations the Spearman test was used. RESULTS: In the sample there were 14/102
      men, 88/102 women with mean age of 52.1 +/- 11.5 years and mean disease duration
      of 10.6 +/- 7.47 years. The mean waist-hip ratio was 0.92 +/- 0.07. According to
      BMI 30.3% had normal weight and 65.5% a total weight above normal. According to
      BSF, 74.5% were normal and 25.5% had depletion of muscular mass; according to
      TSF, 83.3% were normal and 16.7% depleted. Association of nutritional variables
      with gender, rheumatoid factor, age, nodules, and disease activity showed no
      differences (p = NS) except for a lower waist/hip ratio in individuals with
      nodules (p = 0.02) and a modest correlation of TSF with disease duration (p =
      0.02; R = 0.22; 95% CI = 0.01 to 0.40). CONCLUSION: We found a high prevalence of
      overweight and obesity in patients with RA and a small frequency of muscle
      depletion.

PMID- 24878797
TI  - Efficacy and safety of intra and periarticular corticosteroids injections in
      treatment of lupus arthritis.

PMID- 24878798
TI  - Sonographic appearance of pseudopodagra in Behcet's disease.

PMID- 24878799
TI  - [Medical language directed to the rheumatologist: pitfalls and common mistakes].
AB  - The purpose of this article is to stimulate the use of the vernacular by health
      professionals, commenting a few words usually employed in communication between
      rheumatologists. 

PMID- 24878800
TI  - A capacity building approach to increase sports participation in disadvantaged
      urban communities: a multilevel analysis.
AB  - Recent evidence showed that community capacity building is one of the key methods
      to reach health improvements within disadvantaged communities. Physical activity
      and sports participation are important means to reach health improvements. This
      study investigates a capacity building method which aims at increasing sports
      participation in the community, especially for individuals at higher risk of
      sports deprivation. The main aims of the present study, are the following: (1) to
      examine differences in sports participation between individuals living in
      communities implementing a sports-based capacity building program and individuals
      living in communities without such capacity building program and (2) to
      investigate if the community sports program reaches the individuals known to
      experience higher barriers to engage in sports. In Flanders, Belgium, five
      disadvantaged urban communities implementing the community capacity building
      program (program communities) and four without (control communities) were
      selected based on similarity of sociodemographic and environmental
      characteristics. Two hundred adults (aged 18-56 years) per community were
      randomly selected and visited at home to fill out a questionnaire on
      sociodemographics, sports participation, and the community sports program. A
      sample of 414 adults participated in the study. Results showed that adults from
      program communities reported on average 96 min/week more participation in sports
      than their counterparts living in control communities. Furthermore, 61.3% of the
      individuals of program communities indicated to engage in sports, whereas in
      control communities, this was only 42.4%. Respondents at higher risk of sports
      deprivation also engaged in significantly more sports participation in program
      communities than those in control communities. This difference was also noted for
      groups that are not related with sports deprivation. These results are promising
      and plead for a community capacity building approach to increase sports
      participation in disadvantaged communities.

PMID- 24878801
TI  - Electron density analysis of 1-butyl-3-methylimidazolium chloride ionic liquid.
AB  - An analysis of the electron density of different conformers of the 1-butyl-3
      methylimidazolium chloride (bmimCl) ionic liquid by using DFT through the BVP86
      density functional has been obtained within the framework of Bader's atom in
      molecules (AIM), localized orbital locator (LOL), natural bond orbital (NBO), and
      deformed atoms in molecules (DAM). We also present an analysis of the reduced
      density gradients that deliver the non-covalent interaction regions and allow to
      understand the nature of intermolecular interactions. The most polar conformer
      can be characterized as ionic by AIM, LOL, and DAM methods while the most stable
      and the least polar shows shared-type interactions. The NBO method allows to
      comprehend what causes the stabilization of the most stable conformer based on
      analysis of the second-order perturbative energy and the charge transferred among
      the natural orbitals involved in the interaction. 

PMID- 24878802
TI  - Intermediate electrostatic field for the elongation method.
AB  - A simple way to improve the accuracy of the fragmentation methods is proposed.
      The formalism was applied to the elongation (ELG) method at restricted open-shell
      Hartree-Fock (ROHF) level of theory. The alpha-helix conformer of polyglycine was
      taken as a model system. The modified ELG method includes a simplified
      electrostatic field resulting from point-charge distribution of the system's
      environment. In this way the long-distance polarization is approximately taken
      into account. The field attenuates during the ELG process to eventually disappear
      when the final structure is reached. The point-charge distributions for each ELG
      step are obtained from charge sensitivity analysis (CSA) in force-field atoms
      resolution. The presence of the intermediate field improves the accuracy of ELG
      calculations. The errors in total energy and its kinetic and potential
      contributions are reduced by at least one-order of magnitude. In addition the SCF
      convergence of ROHF scheme is improved. 

PMID- 24878803
TI  - AllerTOP v.2--a server for in silico prediction of allergens.
AB  - Allergy is an overreaction by the immune system to a previously encountered,
      ordinarily harmless substance--typically proteins--resulting in skin rash,
      swelling of mucous membranes, sneezing or wheezing, or other abnormal conditions.
      The use of modified proteins is increasingly widespread: their presence in food,
      commercial products, such as washing powder, and medical therapeutics and
      diagnostics, makes predicting and identifying potential allergens a crucial
      societal issue. The prediction of allergens has been explored widely using
      bioinformatics, with many tools being developed in the last decade; many of these
      are freely available online. Here, we report a set of novel models for allergen
      prediction utilizing amino acid E-descriptors, auto- and cross-covariance
      transformation, and several machine learning methods for classification,
      including logistic regression (LR), decision tree (DT), naive Bayes (NB), random
      forest (RF), multilayer perceptron (MLP) and k nearest neighbours (kNN). The best
      performing method was kNN with 85.3% accuracy at 5-fold cross-validation. The
      resulting model has been implemented in a revised version of the AllerTOP server
      (http://www.ddg-pharmfac.net/AllerTOP).

PMID- 24878804
TI  - Redox properties of biscyclopentadienyl uranium(V) imido-halide complexes: a
      relativistic DFT study.
AB  - Calculations of ionization energies (IE) and electron affinities (EA) of a series
      of biscyclopentadienyl imido-halide uranium(V) complexes Cp*2U(=N-2,6-(i)Pr2
      C6H3)(X) with X =  F, Cl, Br, and I, related to the U(IV)/U(V) and U(V)/U(VI)
      redox systems, were carried out, for the first time, using density functional
      theory (DFT) in the framework of the relativistic zeroth order regular
      approximation (ZORA) coupled with the conductor-like screening model (COSMO)
      solvation approach. A very good linear correlation (R(2) =  0.993) was obtained,
      between calculated ionization energies at the ZORA/BP86/TZP level, and the
      experimental half-wave oxidation potentials E1/2. A similar linear correlation
      between the computed electron affinities and the electrochemical reduction
      U(IV)/U(III) potentials (R(2) =  0.996) is obtained. The importance of solvent
      effects and of spin-orbit coupling is definitively confirmed. The molecular
      orbital analysis underlines the crucial role played by the 5f orbitals of the
      central metal whereas the Nalewajski-Mrozek (N-M) bond indices explain well the
      bond distances variations following the redox processes. The IE variation of the
      complexes, i.e., IE(F) < IE(Cl) < IE(Br) < IE(I) is also well rationalized
      considering the frontier MO diagrams of these species. Finally, this work
      confirms the relevance of the Hirshfeld charges analysis which bring to light an
      excellent linear correlation (R(2) =  0.999) between the variations of the
      uranium charges and E1/2 in the reduction process of the U(V) species.

PMID- 24878805
TI  - Theoretical study of methyl group transfer assisted by proton transfer reaction
      in the N-acylated imidates.
AB  - The single methyl group transfer (MGT), double MGT and single MGT assisted by
      proton transfer (PT) that occurs in small biological systems N-methoxy methylene
      formamide and N-hydroxy methylen formamide (NMMF-NHMF) have been investigated
      completely in the present study using density functional theory (DFT) and Moller
      Plesset perturbation (MP2) methods with a 6-31G(d) basis set. The barrier height
      for MGT assisted by PT is significantly lower than those of the single and double
      MGT. Polar solvents decrease the energy barriers. 

PMID- 24878807
TI  - Introductory note.

PMID- 24878806
TI  - DFT investigation of the mismatched base pairs (T-Hg-T)3, (U-Hg-U)3, d(T-Hg-T)2,
      and d(U-Hg-U)2.
AB  - Mismatched T:T and U:U base pairs in DNA and RNA duplexes represent the preferred
      target for mercury(II) cations. In this work, the structural, energetic, and
      electronic properties of the metallo base pairs T-Hg-T and U-Hg-U were
      investigated using density functional theory. In order to evaluate the geometric
      and energetic effects on the stacking interaction, the systems (T-Hg-T)3 and (U
      Hg-U)3 systems as well as the dinucleotide systems d(T-Hg-T)2 and d(U-Hg-U)2 were
      examined. Results show that the exchange-correlation functionals B3LYP-D3 and M06
      L yield reasonable information on these systems that is in agreement with the
      available experimental data. 

PMID- 24878808
TI  - Is there a role of Eastern Europe in cancer biomarkers for personalized cancer
      medicine?

PMID- 24878809
TI  - Translating the molecular analysis of cancer biology into therapeutic concepts.
AB  - The rapidly evolving understanding of tumour biology offers novel opportunities
      for therapeutic interventions. This information already has been used to select
      appropriate systemic treatment. To take full advantage of this knowledge,
      however, the different levels of interaction in an organism need to be integrated
      to link cellular mechanisms, stromal effects and the implications for organs and
      the whole organism. Although very challenging and ambitious, this understanding
      would closely link tumour biology, biomarker validation and rational therapeutic
      decisions. 

PMID- 24878810
TI  - Quality control of ion torrent sequencing library.
AB  - Next-generation sequencing (NSG) is an important method for gathering large
      amounts of sequencing data for different types of applications regarding the
      diagnosis and response to treatment of different diseases. An important step in
      the NGS process is the quality control of sequencing libraries, which can
      influence the yield and efficiency of the sequencing run. This study evaluated
      two different methods for library quality control, Agilent Bioanalyzer and qPCR,
      and showed that both methods can be used. However, as is the case with any
      analytical method, they have their limitations. The Agilent Bioanalyzer
      quantifies only the high quality libraries, but it underestimates their
      concentration, while qPCR also quantifies lower quality libraries, but it
      overestimates their concentration. 

PMID- 24878811
TI  - The value of new high-throughput technologies for diagnosis and prognosis in
      solid tumors.
AB  - Advances in our understanding of the molecular basis of tumors, as well as in the
      technology of DNA analysis, are rapidly changing the landscape of these diseases.
      Traditional approaches such as sequencing methods and arrays have too many
      limits. These have been overcome by the advent of next generation sequencing
      (NGS) methods which facilitate and accelerate the analysis of multiple genes and
      samples. These technologies allow new applications in molecular biology and
      medicine, for example precise analysis of RNA transcripts for gene expression;
      profiling of small RNAs, DNA methylation patterns and histone modification
      analysis; identification of splicing isoforms and of DNA regions that interact
      with regulatory proteins; pharmacogenomics studies and so on. In this review we
      describe recent applications of NGS in genomics, transcriptomics and epigenomics
      for a better comprehension of solid tumor metabolisms. 

PMID- 24878812
TI  - Breast tumor bank: an important resource for developing translational cancer
      research in Romania.
AB  - The development of a breast tumor bank facilitates translational research. Easy
      access to biological specimens allows scientists to translate the outcomes of
      basic science into clinically useful knowledge. The breast tumor bank is
      particularly useful for triple negative breast cancer (TNBC) that is sporadic but
      exhibits the worst prognosis. It serves as a national resource that includes
      biological samples of paraffin-embedded and frozen tumor tissue with
      corresponding pathological and clinical data. During the first two years, the
      bank has accrued data and samples from more than 254 breast cancer cases. Based
      on this information, we observed a higher number of samples with ER (estrogen
      receptor) and PR (progesterone receptor) positive and negative for Her2. Also,
      30% of the total number of cases was defined as TNBC. The use of tumor banks in
      research and diagnosis allows for the design of different studies that can bring
      reliable results that may improve the lives of patients, especially those
      diagnosed with TNBC. 

PMID- 24878813
TI  - An alternative and sensitive method based on LCM and Q-PCR for HER2 testing in
      breast cancer.
AB  - Nowadays, HER2 testing in breast cancer represents a necessity for both
      prognostic and therapy. Despite widespread use of immunohistochemistry (IHC) for
      assessing HER2 status, there are some limitations to identify truly negative or
      positive HER2 cases. Fluorescence in situ hybridization (FISH) or chromogenic in
      situ hybridization (CISH) could solve the equivocal HER2 IHC cases but there is
      no consensus on which is the best method. Consequently, finding a sensitive
      method for HER2 testing is critical for the management of the disease. In
      addition, tumor heterogeneity is an important factor which could affect accuracy
      of molecular diagnostics. Laser capture micro-dissection (LCM) is used to isolate
      pure cell populations from heterogeneous tumor tissue. The combination between
      LCM and quantitative polymerase chain reaction (Q-PCR), the gold standard in
      molecular biology for quantifying gene amplification levels, could define an
      important tool to improve the molecular diagnostics of HER2 status.In our pilot
      study we used LCM and Q-PCR to evaluate HER2 gene amplification for invasive
      breast carcinoma samples. The samples were selected based on HER2 status assessed
      by IHC and CISH. Our results demonstrated high sensitivity of Q-PCR for assessing
      HER2 DNA amplification as well as a good concordance between Q-PCR and IHC/ CISH
      assay. 

PMID- 24878814
TI  - The importance of microRNAs in the stroma-breast cancer cell interplay.
AB  - Breast cancer is one of the most diagnosed cancers in women. Despite outstanding
      progress over the past few years, breast cancer remains the second leading cause
      of cancer-related death among women. This fact emphasizes the need for improved
      diagnostic and prognostic markers, as well as improved understanding of cancer
      environment, including the crosstalk between epithelial and stromal cells. The
      tumor microenvironment is paramount in breast cancer progression and
      dissemination. Accumulating evidence indicates that epigenetic phenomena such as
      microRNAs are extremely important in cancer homeostasis. Through the improved
      understanding of the molecular mechanisms involved in the microenvironment
      mediated promotion of cancer growth and metastasis, novel targets for therapeutic
      intervention or early diagnosis may be identified. 

PMID- 24878815
TI  - Colorectal carcinomas in 2013: the search for powerful prognostic markers is
      still on the go!
AB  - Colorectal cancer (CRC) is the third cause of cancer worldwide after prostate
      cancer and breast cancer. Patients have a survival rate of 5 years, which varies
      between 10 and 95% depending on the CRC stage. Today, the management of patients
      with CRC is based on parameters such as TNM and classic histologic parameters,
      but new molecular and cell markers have been created to improve treatment and
      survival. Determining the expression of a characteristic set of genes either from
      formalin-fixed paraffin-embedded tissues (Onco type DX testTM) or from fresh
      tissues (AGENDIA(c) ColoPrint(r)) has led to encouraging results, but there is a
      need for clinical validation on a large number of patients. Also, next-generation
      sequencing (NGS) technologies may be the next step in the molecular approach of
      CRC tumor samples, allowing tumor characterization by gene signature arrays. In
      addition to molecular markers, evaluation of the presence of cellular markers
      such as circulating tumor cells (CTC) in the blood of patients with CRC can
      optimize prognostic evaluation and response to treatment. CTC isolation methods
      used today have different sensitivities and specificities, due not only to the
      very small number of these cells but also to the epithelial-mesenchymal
      transitional process (EMT). This paper presents the preliminary results of our
      study conducted on CTC isolation in patients with CRC by filtration method
      (Screencells Cyto(r)). This fast and efficient method identifies CTCs and also
      isolates cells in EMT, which explains its high efficiency compared to
      technologies based on immunomagnetic and microfluidic separation reliant on EpCAM
      presence on the cell surface. 

PMID- 24878817
TI  - New horizons in diagnosis and management of endocrine tumors.
AB  - Endocrine tumors were considered relatively infrequent neoplasms. However, during
      the last decades, their frequency gradually increased. The use of imaging
      techniques, guided FNA biopsy, an endoscope camera in the investigation of
      endocrine lesions, permits early diagnosis. At the histological level, new
      applications such as non-biotin containing immunohistochemical detection systems,
      tyramide amplification method, in situ hybridization, FISH, CGH, and other
      molecular techniques have provided better knowledge on the protein and molecular
      background. The investigation of somatostatin and dopamine receptors assists
      targeted therapy of endocrine tumors. Novel treatment modalities have emerged for
      the management of pituitary and gastroenteropancreatic tumors respectively.
      Despite this progress, in some instances, the morphological diagnosis remains
      questionable. Similarities among normal elements, hyperplastic conditions and
      benign or malignant lesions can make separation difficult. The "gray zones"
      representing the overlapping in the sequence of normal parenchyma/ hyperplasia/
      adenoma/ carcinoma signify a difficult and controversial diagnostic task, which
      merits special attention. Furthermore, in most endocrine tumors, the diagnosis of
      carcinoma is justified only in the presence of local or distant metastases. More
      precise guidelines are needed, by improving the currently available criteria, to
      minimize the "gray zones", leading to a more accurate separation of such
      endocrine lesions. 

PMID- 24878816
TI  - Predictive factors to targeted treatment in gastrointestinal carcinomas.
AB  - Most cancers are traditionally treated with either chemotherapeutic agents,
      radiotherapy, or both. Identification of specific molecular characteristics of
      tumors and the advent of molecular-targeted drugs not only enhance the efficacy
      but also decrease the toxicity of treatment. These new therapies may target
      pathways critical to tumor development or specific driver mutations in cancer
      cells. This understanding of the molecular pathways of cancer cells has led to
      the ability to predict cancer development, behaviour and prognosis, as well as
      response or resistance to current therapeutic agents. As a result, pathologic
      analyses play a vital role in the detection of cancer biomarkers, which are
      important not only in the diagnosis of cancers but also in the selection of
      appropriate therapeutic agents and in the development of new targeted therapies. 

PMID- 24878818
TI  - P16(INK4a) protein expression in endocervical, endometrial and metastatic
      adenocarcinomas of extra-uterine origin: diagnostic and clinical considerations.
AB  - Determining the primary site of uterine adenocarcinoma (ADC) may be problematic,
      especially with small specimens. This is particularly important in light of the
      increase of endocervical and endometrial adenocarcinoma and the decrease in
      incidence of squamous cell carcinoma. P16(INK4a) , a member of the INK4 family of
      cell cycle regulatory proteins, plays a critical role. It functions as a negative
      regulator of cell cycle progression and differentiation by controlling the
      activity of the tumor-suppressor protein retinoblastoma (pRb), which regulates
      the cell cycle. Its expression is variable according to the tumoral histotype and
      in metastasis. The aim of this study was to investigate P16(INK4a) expression in
      endocervical, endometrial, and metastatic ADCs of extra-uterine origin. Fifty
      gynaecological biopsies (cervix or endometrium) comprised the study for
      P16(INK4a) determination. Cases were classified as (1) diffuse positive (P), in
      intense nuclear immunostaining and/or cytoplasmic in > 30% of neoplastic cells;
      (2) focal positive (FP), in intense immunostaining in 10% to 30% in isolated
      cells or small groups; and (3) negative (N), in absence of immunostaining or
      weak, sporadic immunostaining in < 10% of neoplastic cells. Included in the study
      were the following: 6 endocervical ADCs, 11 endometrioid-type endometrial ADCs, 5
      endometrial serous papillary ADCs, 7 ovarian ADCs, 4 large intestine ADCs, 1
      breast ADC, 12 not-otherwise-specified (NOS) ADCs, and 4 endocervical biopsy
      without atypia (as control). Diffuse, strong positivity with P16(INK4a) suggests
      an endocervical rather than an endometrial or metastatic ADC. In fact, a
      P16(INK4a) positive immunostaining pattern was prevalent in endocervical (83%)
      and serous papillary ADCs of endometrial or ovarian origin, whereas endometrioid
      ADCs such as metastatic non-ovarian lesions generally presented only focal or
      negative immunostaining. 10/12 cases of ADC-NOS were reclassified using
      P16(INK4a) immunostaining: 2 as endocervical ADCs (2 P), 4 as endometrioid-type
      endometrial ADCs (2 FP, 2 N), 3 as endometrial serous papillary ADCs (3 FP), and
      1 as ovarian serous papillary ADC (1 FP).

PMID- 24878819
TI  - The prognostic value of the Na+/ H+ exchanger regulatory factor 1 (NHERF1)
      protein in cancer.
AB  - NHERF1 (Na+/H+ exchanger regulatory factor) is a scaffolding protein, consists of
      two tandem PDZ domains linked to a carboxyl-terminal ezrin-binding region. NHERF1
      recruits macromolecular complexes at the apical membrane of epithelial cells in
      many epithelial tissues. It is involved in trafficking and regulation of
      transmembrane ion transporters and G protein-coupled receptors. Further, NHERF1
      also linked other molecules involved in cell growth and cancer progression, such
      as PDGFR, PTEN, beta-catenin, EGFR and HER2/neu. In this review, we focus on the
      role of NHERF1 during cancer development. Evidences of its involvement in cancer
      development are present in hepatocellular carcinoma, schwannoma, glioblastoma,
      colorectal cancer and particularly in breast cancer. Recent findings obtained
      from our laboratory show that cytoplasmic NHERF1 expression increases gradually
      in breast cancer during carcinogenesis, and its overexpression is associated with
      aggressive clinical parameters, unfavourable prognosis, and increased tumor
      hypoxia. Interestingly, also nuclear NHERF1 expression seems to play a role both
      in carcinogenesis and progression of colorectal cancer. These data suggest that
      NHERF1 could be a new biomarker of advanced malignancies.

PMID- 24878820
TI  - Quantitative expression of serum biomarkers involved in angiogenesis and
      inflammation, in patients with glioblastoma multiforme: correlations with
      clinical data.
AB  - Glioblastoma multiforme (GBM) represents a very aggressive brain tumor.
      Angiogenesis is the formation of a network of new blood vessels, from preexisting
      ones. It plays an important role in the formation of the tumor, as it supplies it
      with oxygen and nutrients. Angiogenesis and inflammation play essential roles in
      glioblastoma development. These processes are regulated by the balance of a few
      molecules, acting as pro- or antiangiogenic and pro- or anti-inflammatory
      factors. The purpose of our study was to evaluate the expression of 7 markers
      involved in angiogenesis and inflammation pathways in patients with glioblastoma.
      VEGF, PDGF-bb, IGF-1, TGF-beta, TNF-alpha, IL-6 and IL-8 levels were measured
      using the ELISA method, in the preoperative sera of 14 patients with
      histopathologically confirmed glioblastoma multiforme and 32 healthy patients.
      Serum levels of PDGF-bb, IGF-1 and IL-8 were significantly higher in patients
      with GBM, compared to the control group (p-value < 0.01). A statistically
      significant correlation has been found between IGF-1 and IL-6 levels (rho= -0.53,
      p-value < 0.05) and also between TNF-alpha and IL-6 levels (rho=0.60, p-value <
      0.05). Statistically significant associations have been found between the
      presence of low levels of IL-8 and the development of coagulation necrosis (p
      value < 0.05), high levels of VEGF and development of ischemic necrosis (p-value
      < 0.01) and high levels of IL-8 and the development of endothelial hyperplasia (p
      value < 0.05). We have observed no statistically significant associations between
      the serum levels of the markers and the survival rates. 

PMID- 24878821
TI  - Cancer molecular pathobiology in the clinics: concluding remarks.

PMID- 24878824
TI  - Widespread activation of microglial cells in the hippocampus of chronic epileptic
      rats correlates only partially with neurodegeneration.
AB  - Activation of microglial cells (brain macrophages) soon after status epilepticus
      has been suggested to be critical for the pathogenesis of mesial temporal lobe
      epilepsy (MTLE). However, microglial activation in the chronic phase of
      experimental MTLE has been scarcely addressed. In this study, we questioned
      whether microglial activation persists in the hippocampus of pilocarpine-treated,
      epileptic Wistar rats and to which extent it is associated with segmental
      neurodegeneration. Microglial cells were immunostained for the universal
      microglial marker, ionized calcium-binding adapter molecule-1 and the activation
      marker, CD11b (also known as OX42, Mac-1). Using quantitative morphology, i.e.,
      stereology and Neurolucida-based reconstructions, we investigated morphological
      correlates of microglial activation such as cell number, ramification, somatic
      size and shape. We find that microglial cells in epileptic rats feature
      widespread, activation-related morphological changes such as increase in cell
      number density, massive up-regulation of CD11b and de-ramification. The
      parameters show heterogeneity in different hippocampal subregions. For instance,
      de-ramification is most prominent in the outer molecular layer of the dentate
      gyrus, whereas CD11b expression dominates in hilus. Interestingly, microglial
      activation only partially correlates with segmental neurodegeneration. Major
      neuronal death in the hilus, CA3 and CA1 coincides with strong up-regulation of
      CD11b. However, microglial activation is also observed in subregions that do not
      feature neurodegeneration, such as the molecular and granular layer of the
      dentate gyrus. This in vivo study provides solid experimental evidence that
      microglial cells feature widespread heterogeneous activation that only partially
      correlates with hippocampal segmental neuronal loss in experimental MTLE. 

PMID- 24878822
TI  - Estradiol mediates dendritic spine plasticity in the nucleus accumbens core
      through activation of mGluR5.
AB  - Accumulating evidence from human and rodent studies suggests that females are
      more sensitive to the motivating and rewarding properties of drugs of abuse.
      Numerous reports implicate estradiol in enhancing drug-related responses in
      females, yet the neurobiological mechanisms underlying this effect of estradiol
      are unknown. Because dendritic spine plasticity in the nucleus accumbens (NAc) is
      linked to the addictive effects of drugs, we examined the influence of estradiol
      on dendritic spines in this region. Previously our laboratory demonstrated that
      in female medium spiny neurons, estradiol activates metabotropic glutamate
      receptor subtype five (mGluR5), a G protein-coupled receptor already implicated
      in the etiology of drug addiction. Thus, we sought to determine whether mGluR5 is
      a part of the mechanism by which estradiol affects dendritic spine density in the
      NAc. To test this hypothesis, ovariectomized female rats were treated with the
      mGluR5 antagonist, MPEP, or vehicle prior to estradiol (or oil) treatment and 24
      h later dendritic spine density was evaluated by DiI labeling and confocal
      microscopy. We found that estradiol decreased dendritic spine density in the NAc
      core and that pretreatment with MPEP blocked this effect. In contrast, MPEP had
      no effect on dendritic spine density in the NAc shell or CA1 region of the
      hippocampus, two regions in which estradiol increased the density of dendritic
      spines. As dendritic spine plasticity in the NAc core has behavioral consequences
      for drug addiction, these data provide a clue as to how estradiol acts in females
      to enhance behavioral responses to drugs of abuse. 

PMID- 24878825
TI  - Behavioral and neurophysiological evidence for the enhancement of cognitive
      control under dorsal pallidal deep brain stimulation in Huntington's disease.
AB  - Deep brain stimulation of the dorsal pallidum (globus pallidus, GP) is
      increasingly considered as a surgical therapeutic option in Huntington's disease
      (HD), but there is need to identify outcome measures useful for clinical trials.
      Computational models consider the GP to be part of a basal ganglia network
      involved in cognitive processes related to the control of actions. We examined
      behavioural and event-related potential (ERP) correlates of action control (i.e.,
      error monitoring) and evaluated the effects of deep brain stimulation (DBS). We
      did this using a standard flanker paradigm and evaluated error-related ERPs.
      Patients were recruited from a prospective pilot trial for pallidal DBS in HD
      (trial number NCT00902889). From the initial four patients with Huntington's
      chorea, two patients with chronic external dorsal pallidum stimulation were
      available for follow-up and able to perform the task. The results suggest that
      the external GP constitutes an important basal ganglia element not only for error
      processing and behavioural adaptation but for general response monitoring
      processes as well. Response monitoring functions were fully controllable by
      switching pallidal DBS stimulation on and off. When stimulation was switched off,
      no neurophysiological and behavioural signs of error and general performance
      monitoring, as reflected by the error-related negativity and post-error slowing
      in reaction times were evident. The modulation of response monitoring processes
      by GP-DBS reflects a side effect of efforts to alleviate motor symptoms in HD.
      From a clinical neurological perspective, the results suggest that DBS in the
      external GP segment can be regarded as a potentially beneficial treatment with
      respect to cognitive functions. 

PMID- 24878823
TI  - Interindividual differences in cognitive flexibility: influence of gray matter
      volume, functional connectivity and trait impulsivity.
AB  - Cognitive flexibility, a core aspect of executive functioning, is required for
      the speeded shifting between different tasks and sets. Using an interindividual
      differences approach, we examined whether cognitive flexibility, as assessed by
      the Delis-Kaplan card-sorting test, is associated with gray matter volume (GMV)
      and functional connectivity (FC) of regions of a core network of multiple
      cognitive demands as well as with different facets of trait impulsivity. The core
      multiple-demand network was derived from three large-scale neuroimaging meta
      analyses and only included regions that showed consistent associations with
      sustained attention, working memory as well as inhibitory control. We tested to
      what extent self-reported impulsivity as well as GMV and resting-state FC in this
      core network predicted cognitive flexibility independently and incrementally. Our
      analyses revealed that card-sorting performance correlated positively with GMV of
      the right anterior insula, FC between bilateral anterior insula and midcingulate
      cortex/supplementary motor area as well as the impulsivity dimension
      "Premeditation." Importantly, GMV, FC and impulsivity together accounted for more
      variance of card-sorting performance than every parameter alone. Our results
      therefore indicate that various factors contribute individually to cognitive
      flexibility, underlining the need to search across multiple modalities when
      aiming to unveil the mechanisms behind executive functioning. 

PMID- 24878826
TI  - Finding the lost open-circuit voltage in polymer solar cells by UV-ozone
      treatment of the nickel acetate anode buffer layer.
AB  - Efficient polymer solar cells (PSCs) with enhanced open-circuit voltage (Voc) are
      fabricated by introducing solution-processed and UV-ozone (UVO)-treated nickel
      acetate (O-NiAc) as an anode buffer layer. According to X-ray photoelectron
      spectroscopy data, NiAc partially decomposed to NiOOH during the UVO treatment.
      NiOOH is a dipole species, which leads to an increase in the work function (as
      confirmed by ultraviolet photoemission spectroscopy), thus benefitting the
      formation of ohmic contact between the anode and photoactive layer and leading to
      increased Voc. In addition, the UVO treatment improves the wettability between
      the substrate and solvent of the active layer, which facilitates the formation of
      an upper photoactive layer with better morphology. Further, the O-NiAc layer can
      decrease the series resistance (Rs) and increase the parallel resistance (Rp) of
      the devices, inducing enhanced Voc in comparison with the as-prepared NiAc
      buffered control devices without UVO treatment. For PSCs based on the P3HT:PCBM
      system, Voc increases from 0.50 to 0.60 V after the NiAc buffer layer undergoes
      UVO treatment. Similarly, in the P3HT:ICBA system, the Voc value of the device
      with a UVO-treated NiAc buffer layer increases from 0.78 to 0.88 V, showing an
      enhanced power conversion efficiency of 6.64%. 

PMID- 24878829
TI  - Umbilical pigmentation in Peutz-Jeghers syndrome.

PMID- 24878828
TI  - Identification of a novel familial FGF16 mutation in metacarpal 4-5 fusion.

PMID- 24878827
TI  - A comparative controlled trial comparing the effects of yoga and walking for
      overweight and obese adults.
AB  - BACKGROUND: Walking and yoga have been independently evaluated for weight
      control; however, there are very few studies comparing the 2 with randomization.
      MATERIAL AND METHODS: The present study compared the effects of 90 minutes/day
      for 15 days of supervised yoga or supervised walking on: (i) related
      biochemistry, (ii) anthropometric variables, (iii) body composition, (iv)
      postural stability, and (v) bilateral hand grip strength in overweight and obese
      persons. Sixty-eight participants, of whom 5 were overweight (BMI >=25 kg/m2) and
      63 were obese (BMI >=30 kg/m2; group mean age +/-S.D., 36.4+/-11.2 years; 35
      females), were randomized as 2 groups - (i) a yoga group and (ii) a walking group
      - given the same diet. RESULTS: All differences were pre-post changes within each
      group. Both groups showed a significant (p<0.05; repeated measures ANOVA, post
      hoc analyses) decrease in: BMI, waist circumference, hip circumference, lean
      mass, body water, and total cholesterol. The yoga group increased serum leptin
      (p<0.01) and decreased LDL cholesterol (p<0.05). The walking group decreased
      serum adiponectin (p<0.05) and triglycerides (p<0.05). CONCLUSIONS: Both yoga and
      walking improved anthropometric variables and serum lipid profile in overweight
      and obese persons. The possible implications are discussed.

PMID- 24878830
TI  - Dissociable mechanisms underlying individual differences in visual working memory
      capacity.
AB  - Individuals scoring relatively high on measures of working memory tend to be more
      proficient at controlling attention to minimize the effect of distracting
      information. It is currently unknown whether such superior attention control
      abilities are mediated by stronger suppression of irrelevant information,
      enhancement of relevant information, or both. Here we used steady-state visual
      evoked potentials (SSVEPs) with the Eriksen flanker task to track simultaneously
      the attention to relevant and irrelevant information by tagging target and
      distractors with different frequencies. This design allowed us to dissociate
      attentional biasing of perceptual processing (via SSVEPs) and stimulus processing
      in the frontal cognitive control network (via time-frequency analyses of EEG
      data). We show that while preparing for the upcoming stimulus, high- and low-WMC
      individuals use different strategies: High-WMC individuals show attentional
      suppression of the irrelevant stimuli, whereas low-WMC individuals demonstrate
      attentional enhancement of the relevant stimuli. Moreover, behavioral performance
      was predicted by trial-to-trial fluctuations in strength of distractor
      suppression for high-WMC participants. We found no evidence for WMC-related
      differences in cognitive control network functioning, as measured by midfrontal
      theta-band power. Taken together, these findings suggest that early suppression
      of irrelevant information is a key underlying neural mechanism by which superior
      attention control abilities are implemented. 

PMID- 24878832
TI  - How do you define age?

PMID- 24878831
TI  - Determination of free vancomycin, ceftriaxone, cefazolin and ertapenem in plasma
      by ultrafiltration: impact of experimental conditions.
AB  - Ultrafiltration is a rapid and convenient method to determine the free
      concentrations of drugs. In the present work, we aimed to develop an
      ultrafiltration method which is appropriate for routine determination of the free
      fraction of vancomycin and highly protein bound beta-lactams such as ertapenem,
      ceftriaxone and cefazolin in plasma from intensive care unit patients. Different
      filter types and experimental conditions (molecular weight cut-off, centrifugal
      force and time, pH, temperature) were evaluated and found to have influence on
      the result. In the final protocol, serum or plasma was buffered to pH 7.4-7.5,
      ultrafiltered at 1000*g at 37 degrees C for 20min using Nanosep Omega 10K filters
      and subsequently analysed for the antibiotics by RP-HPLC with UV detection. The
      data from our investigation suggest to aim physiological conditions, i.e. 37
      degrees C and pH 7.4, and low to moderate relative centrifugal forces in order to
      get reliable results. With regard to the chromatographic separation, modulation
      of the pH in the range of 2.5-7.0 allows to determine several beta-lactams
      isocratically and/or to avoid interferences by co-administered drugs. 

PMID- 24878833
TI  - Managing hyperlipidemia. The updated cholesterol treatment guidelines.
AB  - : The ACC/AHA 2013 cholesterol treatment guidelines focus on lowering the risk of
      heart disease and stroke and not on targeted treatment goals in adult patients.
      This article offers a synopsis of the new guidelines and how to apply them in
      clinical practice. 

PMID- 24878834
TI  - The CMS Annual Wellness Visit: bridging the gap.
AB  - In 2011, Medicare beneficiaries became eligible for an Annual Wellness Visit,
      which includes a health risk assessment and a customized wellness or personal
      prevention plan. This article discusses strategies for performing the exam in a
      primary care setting.

PMID- 24878835
TI  - To eat or not to eat; is that really the question? An evaluation of problematic
      eating behaviors and mental health among bariatric surgery candidates.
AB  - Problematic eating behaviors, such as emotional eating, and food addiction, may
      affect weight; however, little is known about these eating behaviors, especially
      among those seeking bariatric surgery. Therefore, the purpose of this study was
      to estimate the prevalence of problematic eating behaviors and to investigate
      their relationship with other eating behaviors, body mass index (BMI), and
      psychiatric symptoms. There were 142 patients who completed a required
      psychiatric evaluation prior to bariatric surgery. Of these, 16.9 % met criteria
      for a food addiction and 25.4-40.7 % endorsed emotional eating, depending on type
      of emotional eating. The number of food addiction symptoms endorsed was related
      to emotional eating. Both food addiction and emotional eating were related to
      anxiety and depressive symptoms. However, surprisingly, BMI was not related to a
      food addiction diagnosis, emotional eating scores, or psychiatric symptoms.
      Results from this study suggest that problematic eating behaviors are occurring
      among bariatric surgery candidates. Furthermore, this study may help to address
      the conflicting research regarding the effects of psychiatric symptoms on weight
      loss outcomes. Perhaps it is the problematic eating behaviors (e.g., food
      addiction and emotional eating) that are associated with psychiatric symptoms
      that could be influencing outcomes. Future research should evaluate treatments
      for problematic eating behaviors and whether treatments improve weight-loss
      success. 

PMID- 24878836
TI  - Neuregulin-ErbB4 signaling in the developing lung alveolus: a brief review.
AB  - Lung immaturity is the major cause of morbidity and mortality in premature
      infants, especially those born <28 weeks gestation. Proper lung development from
      23-28 weeks requires coordinated cell proliferation and differentiation. Infants
      born at this age are at high risk for respiratory distress syndrome (RDS), a lung
      disease characterized by insufficient surfactant production due to immaturity of
      the alveoli and its constituent cells in the lung. The ErbB4 receptor and its
      stimulation by neuregulin (NRG) plays a critical role in surfactant synthesis by
      alveolar type II epithelial cells. In this review, we first provide an
      introduction to normal human alveolar development, followed by a discussion of
      the neuregulin and ErbB4-mediated mechanisms regulating alveolar development and
      surfactant production. 

PMID- 24878838
TI  - Foot drop after a suicide attempt.

PMID- 24878837
TI  - Sensitivity of quantitative UTE MRI to the biomechanical property of the
      temporomandibular joint disc.
AB  - PURPOSE: To quantify MR properties of discs from cadaveric human
      temporomandibular joints (TMJ) using quantitative conventional and ultrashort
      time-to-echo magnetic resonance imaging (UTE MRI) techniques and to corroborate
      regional variation in the MR properties with that of biomechanical indentation
      stiffness. METHODS: This study was exempt from the institutional review board
      approval. Cadaveric (four donors, two females, 74 +/- 10.7 years) TMJs were
      sliced (n = 14 slices total) sagittally and imaged using quantitative techniques
      of conventional spin echo T2 (SE T2), UTE T2*, and UTE T1rho. The discs were then
      subjected to biomechanical indentation testing, which is performed by compressing
      the tissue with the blunt end of a small solid cylinder. Regional variations in
      MR and indentation stiffness were correlated. TMJ of a healthy volunteer was also
      imaged to show in vivo feasibility. RESULTS: Using the ME SE T2 and the UTE T1rho
      techniques, a significant (each p < 0.0001) inverse relation between MR and
      indentation stiffness properties was observed for the data in the lower range of
      stiffness. However, the strength of correlation was significantly higher (p <
      0.05) for UTE T1rho (R(2) = 0.42) than SE T2 (R(2) = 0.19) or UTE T2* (R(2) =
      0.02, p = 0.1) techniques. CONCLUSION: The UTE T1rho technique, applicable in
      vivo, facilitated quantitative evaluation of TMJ discs and showed a high
      sensitivity to biomechanical softening of the TMJ discs. With additional work,
      the technique may become a useful surrogate measure for loss of biomechanical
      integrity of TMJ discs reflecting degeneration.

PMID- 24878839
TI  - Whole-body muscle MRI to detect myopathies in non-extrapyramidal bent spine
      syndrome.
AB  - OBJECTIVE: Bent spine syndrome (BSS), defined as an abnormal forward flexion of
      the trunk resolving in supine position, is usually related to parkinsonism, but
      can also be encountered in myopathies. This study evaluates whole-body muscle MRI
      (WB-mMRI) as a tool for detecting underlying myopathy in non-extrapyramidal BSS.
      MATERIALS AND METHODS: Forty-three patients (90 % women; 53-86 years old) with a
      non-extrapyramidal BSS were prospectively included. All underwent a 1.5-T WB-mMRI
      and a nerve conduction study. Muscle biopsy was performed if a myopathy could not
      be eliminated based on clinical examination and all tests. Systematic MRI
      interpretation focused on peripheral and axial muscle injury; spinal posture and
      incidental findings were also reported. RESULTS: WB-mMRI was completed for all
      patients, with 13 muscle biopsies ultimately needed and myopathy revealed as the
      final etiological diagnosis in five cases (12 %). All biopsy-proven myopathies
      were detected by the WB-mMRI. Relevant incidental MRI findings were made in seven
      patients. CONCLUSIONS: This study supports WB-mMRI as a sensitive and feasible
      tool for detecting myopathy in BSS patients. Associated with
      electroneuromyography, it can better indicate when a muscle biopsy is needed and
      guide it when required. Rigorous radiological interpretation is mandatory, so as
      not to miss incidental findings of clinical consequence.

PMID- 24878840
TI  - Combination of biobarcode assay with on-chip capillary electrophoresis for
      ultrasensitive and multiplex biological agent detection.
AB  - Early diagnosis of biological agents is of paramount importance to prevent the
      casualties and fatal disease in human during bioterrorism or biological warfare.
      In this study, we reported an efficient and sensitive multiplex biological agent
      detection method based on the DNA biobarcode assay and the micro-capillary
      electrophoresis (MUCE) technology. Monoplex as well as multiplex pathogen
      identification was performed using five targets including Bacillus anthracis,
      Francisella tularensis, Yersinia pestis, Vaccinia virus and Botulinum toxin A.
      Through the DNA biobarcode assay process, the magnetic microparticle-pathogen
      polystyrene microbead complexes were formed, and the FAM labeled single stranded
      barcode DNA could be released from the complexes upon denaturation. Different
      lengths of a barcode DNA were designed to designate each pathogen, so that the
      specific peak elution time in the capillary electrophoresis on a chip allows us
      to distinguish the target with high accuracy within 3 min. We improved the
      assignment accuracy of the peak in the electropherogram by adding two bracket
      ladders. Owing to the abundant amount of barcode DNAs, the presence of B.
      anthracis, F. tularensis, Y. pestis, Vaccinia virus was confirmed with a limit of
      detection of 50CFU/mL, while Botulinum toxin A was analyzed even at a
      concentration of 12.5 ag/mL. Multiple pathogen detection was also successfully
      conducted in a phosphate buffered saline (PBS) as well as a serum medium with
      background of other pathogens. Thus, our analytical platform based on the
      biobarcode assay and on-chip CE analysis provides rapid, sensitive, multiplex,
      and accurate biological agent identification.

PMID- 24878841
TI  - Demonstration of the effect of generic anatomical divisions versus clinical
      protocols on computed tomography dose estimates and risk burden.
AB  - OBJECTIVE: Choosing to undertake a CT scan relies on balancing risk versus
      benefit, however risks associated with CT scanning have generally been limited to
      broad anatomical locations, which do not provided adequate information to
      evaluate risk against benefit. Our study aimed to determine differences in
      radiation dose and risk estimates associated with modern CT scanning examinations
      when computed for clinical protocols compared with those using anatomical area.
      METHODS: Technical data were extracted from a tertiary hospital Picture Archiving
      Communication System for random samples of 20-40 CT examinations per adult
      clinical CT protocol. Organ and whole body radiation dose were calculated using
      ImPACT Monte Carlo simulation software and cancer incidence and mortality
      estimated using BEIR VII age and gender specific lifetime attributable risk
      weights. RESULTS: Thirty four unique CT protocols were identified by our study.
      When grouped according to anatomic area the radiation dose varied substantially,
      particularly for abdominal protocols. The total estimated number of incident
      cancers and cancer related deaths using the mean dose of anatomical area were 86
      and 69 respectively. Using more specific protocol doses the estimates rose to 214
      and 138 incident cancers and cancer related deaths, at least doubling the burden
      estimated. CONCLUSIONS: Modern CT scanning produces a greater diversity of
      effective doses than much of the literature describes; where a lack of focus on
      actual scanning protocols has produced estimates that do not reflect the range
      and complexity of modern CT practice. To allow clinicians, patients and policy
      makers to make informed risk versus benefit decisions the individual and
      population level risks associated with modern CT practices are essential.

PMID- 24878842
TI  - Measuring social exclusion in routine public health surveys: construction of a
      multidimensional instrument.
AB  - INTRODUCTION: Social exclusion is considered a major factor in the causation and
      maintenance of health inequalities, but its measurement in health research is
      still in its infancy. In the Netherlands the Institute for Social Research (SCP)
      developed an instrument to measure the multidimensional concept of social
      exclusion in social and economic policy research. Here, we present a method to
      construct a similar measure of social exclusion using available data from public
      health surveys. METHODS: Analyses were performed on data from the health
      questionnaires that were completed by 20,877 adults in the four largest cities in
      the Netherlands. From each of the four questionnaires we selected the items that
      corresponded to those of the SCP-instrument. These were entered into a nonlinear
      canonical correlation analysis. The measurement properties of the resulting
      indices and dimension scales were assessed and compared to the SCP-instrument.
      RESULTS: The internal consistency of the indices and most of the dimension scales
      were adequate and the internal structure of the indices was as expected. Both
      generalisabiliy and construct validity were good: in all datasets strong
      associations were found between the index and a number of known risk factors of
      social exclusion. A limitation of content validity was that the dimension "lack
      of normative integration" could not be measured, because no relevant items were
      available. CONCLUSIONS: Our findings indicate that a measure for social exclusion
      can be constructed with available health questionnaires. This provides
      opportunities for application in public health surveillance systems in the
      Netherlands and elsewhere in the world.

PMID- 24878843
TI  - Induced circular dichroism of polyoxometalates via electrostatic encapsulation
      with chiral organic cations.
AB  - To explore the principle of chiral induction in inorganic clusters, chiral
      organic cations with two stereocenters, R- and S-BPEA, are used to encapsulate a
      series of polyoxometalates (POMs) bearing different structures and transition
      absorption bands in aqueous solution, constructing a series of chiral
      supramolecular complexes. Due to the induction of chiral organic cations, POMs
      possessing both chiral and achiral structures show an induced circular dichroism
      (ICD) effect. ICD signals in the absorption bands corresponding to ligand to
      metal charge transfer (LMCT) transitions, d-d transitions and intervalence charge
      transfer (IVCT) transitions are observed for different complexes. Moreover, the
      ICD of the POMs exhibits a direct correlation with the degree of POM distortion
      and the distance between the chiral center and the POM surface. The encapsulation
      of POMs with chiral organic cations via electrostatic interactions provides a
      facile and effective method for constructing optically pure POM-based materials. 

PMID- 24878844
TI  - Dose-response of superparamagnetic iron oxide labeling on mesenchymal stem cells
      chondrogenic differentiation: a multi-scale in vitro study.
AB  - AIM: The aim of this work was the development of successful cell therapy
      techniques for cartilage engineering. This will depend on the ability to monitor
      non-invasively transplanted cells, especially mesenchymal stem cells (MSCs) that
      are promising candidates to regenerate damaged tissues. METHODS: MSCs were
      labeled with superparamagnetic iron oxide particles (SPIO). We examined the
      effects of long-term labeling, possible toxicological consequences and the
      possible influence of progressive concentrations of SPIO on chondrogenic
      differentiation capacity. RESULTS: No influence of various SPIO concentrations
      was noted on human bone marrow MSC viability or proliferation. We demonstrated
      long-term (4 weeks) in vitro retention of SPIO by human bone marrow MSCs seeded
      in collagenic sponges under TGF-beta1 chondrogenic conditions, detectable by
      Magnetic Resonance Imaging (MRI) and histology. Chondrogenic differentiation was
      demonstrated by molecular and histological analysis of labeled and unlabeled
      cells. Chondrogenic gene expression (COL2A2, ACAN, SOX9, COL10, COMP) was
      significantly altered in a dose-dependent manner in labeled cells, as were GAG
      and type II collagen staining. As expected, SPIO induced a dramatic decrease of
      MRI T2 values of sponges at 7T and 3T, even at low concentrations. CONCLUSIONS:
      This study clearly demonstrates (1) long-term in vitro MSC traceability using
      SPIO and MRI and (2) a deleterious dose-dependence of SPIO on TGF-beta1 driven
      chondrogenesis in collagen sponges. Low concentrations (12.5-25 ug Fe/mL) seem
      the best compromise to optimize both chondrogenesis and MRI labeling.

PMID- 24878846
TI  - Effects of ankle-foot orthoses on mediolateral foot-placement ability during post
      stroke gait.
AB  - BACKGROUND: Accurate and precise mediolateral foot placement is important for
      balance during gait, but is impaired post stroke. Mediolateral foot placement may
      be improved with ankle-foot orthosis use. OBJECTIVE: The purpose of this study
      was to determine whether an ankle-foot orthosis improves mediolateral foot
      placement ability during post-stroke ambulation. STUDY DESIGN: Crossover trial
      with randomized order of conditions tested. METHODS: The accuracy and precision
      of mediolateral foot placement was quantified while subjects targeted four
      different randomized step widths. Subjects were tested with and without their
      regular non-rigid ankle-foot orthosis in two separate visits (order randomized).
      RESULTS: While ankle-foot orthosis use corrected foot and ankle alignment (i.e.
      significantly decreased mid-swing plantar flexion, p = 0.000), effects of ankle
      foot orthosis use on hip hiking (p = 0.545), circumduction (p = 0.179), coronal
      plane hip range of motion (p = 0.06), and mediolateral foot-placement ability (p
      = 0.537) were not significant. CONCLUSION: While ankle-foot orthosis-mediated
      equinovarus correction of the affected foot and ankle was not associated with
      improved biomechanics of walking (i.e. proximal ipsilateral hip kinematics or
      mediolateral foot-placement ability), it may affect other aspects of balance that
      were not tested in this study (e.g. proprioception, cerebellar, vestibular, and
      cognitive mechanisms). CLINICAL RELEVANCE: Studies that investigate the effect of
      ankle-foot orthosis on gait can help advance stroke rehabilitation by documenting
      the specific gait benefits of ankle-foot orthosis use. In this study, we
      investigated the effect of ankle-foot orthosis use on mediolateral foot-placement
      ability, an aspect of gait important for maintaining balance.

PMID- 24878845
TI  - Anti-fibrotic actions of interleukin-10 against hypertrophic scarring by
      activation of PI3K/AKT and STAT3 signaling pathways in scar-forming fibroblasts.
AB  - BACKGROUND: The hypertrophic scar (HS) is a serious fibrotic skin condition and a
      major clinical problem. Interleukin-10 (IL-10) has been identified as a
      prospective scar-improving compound based on preclinical trials. Our previous
      work showed that IL-10 has anti-fibrotic effects in transforming growth factor
      (TGF)-beta1-stimulated fibroblasts, as well as potential therapeutic benefits for
      the prevention and reduction of scar formation. However, relatively little is
      known about the mechanisms underlying IL-10-mediated anti-fibrotic and scar
      improvement actions. OBJECTIVE: To explore the expression of the IL-10 receptor
      in human HS tissue and primary HS fibroblasts (HSFs), and the molecular
      mechanisms contributing to the anti-fibrotic and scar-improvement capabilities of
      IL-10. METHODS: Expression of the IL-10 receptor was assessed in HS tissue and
      HSFs by immunohistochemistry, immunofluorescence microscopy, and polymerase chain
      reaction analysis. Primary HSFs were treated with IL-10, a specific
      phosphatidylinositol 3 kinase (PI3K) inhibitor (LY294002) or a function-blocking
      antibody against the IL-10 receptor (IL-10RB). Next, Western blot analysis was
      used to evaluate changes in the phosphorylation status of AKT and signal
      transducers and activators of transcription (STAT) 3, as well as the expression
      levels of fibrosis-related proteins. RESULTS: HS tissue and primary HSFs were
      characterized by expression of the IL-10 receptor and by high expression of
      fibrotic markers relative to normal controls. Primary HSFs expressed the IL-10
      receptor, while IL-10 induced AKT and STAT3 phosphorylation in these cells. In
      addition, LY294002 blocked AKT and STAT phosphorylation, and also up-regulated
      expression levels of type I and type III collagen (Col 1 and Col 3) and alpha
      smooth muscle actin (alpha-SMA) in IL-10-treated cells. Similarly, IL-10RB
      reduced STAT3/AKT phosphorylation and blocked the IL-10-mediated mitigation of
      fibrosis in HSFs. CONCLUSION: IL-10 apparently inhibits fibrosis by activating
      AKT and STAT3 phosphorylation downstream of the IL-10 receptor, and by
      facilitating crosstalk between the PI3K/AKT and STAT3 signal transduction
      pathways.

PMID- 24878847
TI  - Scapular resting position, shoulder pain and function in disabled athletes.
AB  - BACKGROUND: Despite the fact that the number of disabled individuals
      participating in sports is increasing, there are only sparse reports in the
      literature concerning overuse injuries. OBJECTIVES: The purpose of this study was
      to compare scapular resting position, shoulder pain, and function in wheelchair
      basketball, amputee soccer, and disabled table tennis players. STUDY DESIGN:
      Descriptive study. METHODS: A total of 63 disabled players from amputee soccer,
      wheelchair basketball, and disabled table tennis participated in our study.
      Scapular resting position was taken as primary outcome; pain and function were
      taken as secondary outcome measurements. Scapular resting position was evaluated
      with Lateral Scapular Slide Test. Visual Analog Scale was used for evaluating
      shoulder pain intensity. Quick disabilities of the arm, shoulder, and hand
      questionnaire were used to assess upper extremity function. RESULTS: There was a
      significant difference in shoulder pain, function, and scapular resting position
      in all groups (p < 0.05). Paired comparisons between amputee soccer and
      wheelchair basketball players and also amputee soccer and disabled table tennis
      showed difference for all measurement parameters (p < 0.05). CONCLUSION: When the
      results are evaluated, it may be stated that amputee soccer players have better
      scapular resting position than other sports. Crutch usage may not negatively
      affect scapular resting position and perceived function as much as wheelchair
      usage. Exercise techniques for shoulder and resting position could be included in
      training programs of disabled athletes. CLINICAL RELEVANCE: Wheelchair/crutch
      usage is a risk, and special exercise techniques for shoulder and dyskinesis
      could be included in training programs to prevent injury. However, it may not
      just be important for wheelchair athletes, it may also be important for amputee
      soccer players. In particular, total upper extremity evaluations and exercises
      could be added within exercise programs.

PMID- 24878848
TI  - Effect of bovine apo-lactoferrin on the growth and virulence of Actinobacillus
      pleuropneumoniae.
AB  - Actinobacillus pleuropneumoniae (App) is a Gram-negative bacterium that causes
      porcine pleuropneumonia, leading to economic losses in the swine industry. Due to
      bacterial resistance to antibiotics, new treatments for this disease are
      currently being sought. Lactoferrin (Lf) is an innate immune system glycoprotein
      of mammals that is microbiostatic and microbicidal and affects several bacterial
      virulence factors. The aim of this study was to investigate whether bovine iron
      free Lf (BapoLf) has an effect on the growth and virulence of App. Two serotype 1
      strains (reference strain S4074 and the isolate BC52) and a serotype 7 reference
      strain (WF83) were analyzed. First, the ability of App to grow in iron-charged
      BLf was discarded because in vivo, BapoLf sequesters iron and could be a
      potential source of this element favoring the infection. The minimum inhibitory
      concentration of BapoLf was 14.62, 11.78 and 10.56 uM for the strain BC52, S4074
      and WF83, respectively. A subinhibitory concentration (0.8 uM) was tested by
      assessing App adhesion to porcine buccal epithelial cells, biofilm production,
      and the secretion and function of toxins and proteases. Decrease in adhesion (24
      42 %) was found in the serotype 1 strains. Biofilm production decreased (27 %)
      for only the strain 4074 of serotype 1. Interestingly, biofilm was decreased (60
      70 %) in the three strains by BholoLf. Hemolysis of erythrocytes and toxicity
      towards HeLa cells were not affected by BapoLf. In contrast, proteolytic activity
      in all strains was suppressed in the presence of BapoLf. Finally, oxytetracycline
      produced synergistic effect with BapoLf against App. Our results suggest that
      BapoLf affects the growth and several of the virulence factors in App. 

PMID- 24878849
TI  - Re-membrance.
AB  - Traced sufficiently remotely, all people, profanum vulgus, share a common
      familial and linguistic heritage. Several Occidental and Oriental
      religiophilosophical traditions and General Systems (neuro-linguistic/neuro
      semantic) Theory propound that resolution of personal illness and intra- and
      inter-generational psychological conflicts among individuals and within society
      mandates a figurative, if not a literal return, to the source of conflict or
      contention-to RE-MEMBER with that source-if healing, peace, resolution, concord,
      solace, sustenance, and wholeness are to be achieved. Words that communicate
      effectively, linguistic symbols such as water and the cross, and the action of
      laying-on-of-hands are methodologies that reaffirm a personal commonality among
      all traditions and facilitate RE-MEMBRANCE. For those who adhere to the Judeo
      Christocentric tradition-who are called and chosen to witness and serve through
      the sacrament of baptism-healing, support, and sustenance are achieved by RE
      MEMBRANCE through the Triune God.

PMID- 24878850
TI  - A20: attractive without showing cleavage.

PMID- 24878852
TI  - Impacts of TCDD and MeHg on DNA methylation in zebrafish (Danio rerio) across two
      generations.
AB  - This study aimed to investigate whether dioxin (TCDD) and methylmercury (MeHg)
      pose a threat to offspring of fish exposed to elevated concentrations of these
      chemicals via epigenetic-based mechanisms. Adult female zebrafish were fed diets
      added either 20 MUg/kg 2,3,7,8 TCDD or 10 mg/kg MeHg for 47 days, or 10 mg/kg 5
      aza-2'-deoxycytidine (5-AZA), a hypomethylating agent, for 32 days, and bred with
      unexposed males in clean water to produce F1 and F2 offspring. Global DNA
      methylation, promoter CpG island methylation and target gene transcription in
      liver of adult females and in 3 days post fertilization (dpf) F1 and F2 embryos
      were determined with HPLC, a novel CpG island tiling array containing 54,933
      different probes and RT-qPCR, respectively. The results showed that chemical
      treatment had no significant effect on global DNA methylation levels in F1 (MeHg
      and TCDD) and F2 (MeHg) embryos and only a limited number of genes were
      identified with altered methylation levels at their promoter regions. CYP1A1
      transcription, an established marker of TCDD exposure, was elevated 27-fold in F1
      embryos compared to the controls, matching the high levels of CYP1A1 expression
      observed in F0 TCDD-treated females. This suggests that maternal transfer of TCDD
      is a significant route of exposure for the F1 offspring. In conclusion, the
      selected doses of TCDD and MeHg, two chemicals often found in high concentrations
      in fish, appear to have only modest effects on DNA methylation in F1 (MeHg and
      TCDD) and F2 (MeHg) embryos of treated F0 females.

PMID- 24878851
TI  - The deubiquitinase activity of A20 is dispensable for NF-kappaB signaling.
AB  - A20 has been suggested to limit NF-kappaB activation by removing regulatory
      ubiquitin chains from ubiquitinated substrates. A20 is a ubiquitin-editing enzyme
      that removes K63-linked ubiquitin chains from adaptor proteins, such as RIP1, and
      then conjugates them to K48-linked polyubiquitin chains to trigger proteasomal
      degradation. To determine the role of the deubiquitinase function of A20 in
      downregulating NF-kappaB signaling, we have generated a knock-in mouse that lacks
      the deubiquitinase function of A20 (A20-OTU mice). These mice are normal and have
      no signs of inflammation, have normal proportions of B, T, dendritic, and myeloid
      cells, respond normally to LPS and TNF, and undergo normal NF-kappaB activation.
      Our results thus indicate that the deubiquitinase activity of A20 is dispensable
      for normal NF-kappaB signaling. 

PMID- 24878853
TI  - Effects of one minute and ten minutes of walking activity in rats with arthritis
      induced by complete Freund's adjuvant on pain and edema symptoms.
AB  - This study evaluated the effects of two protocols of exercise on nociception,
      edema and cell migration in rats with CFA-induced arthritis. Female Wistar rats
      (200 - 250 g, n = 50) was monoarthritis-induced by complete Freund's adjuvant
      (CFA; Mycobacterium butyricum, 0.5 mg/mL; 50 MUL) into the right knee joint (TF;
      n = 24) or right ankle joint (TT; n = 26). Incapacitation was measured by the paw
      elevation time (TEP; s) in 1-min periods of observation. The edema of the knee or
      ankle joints was evaluated by the variation of the articular diameter (DA, cm)
      and by the paw volume variation (EP, mL), respectively. Both were measured during
      10 consecutive days. Two protocols of exercise were performed: (a) in the
      constant exercise group (TF, n = 6; TT, n = 6) performing 1 minute of daily
      exercise on the cylinder; (b) variable exercise group (TF, n = 6; TT, n = 7), the
      exercise increased by 1 minute per day. The control groups (TF, n = 12; TT, n =
      13) didn't perform the exercise. After 10 days, the animals were euthanized for
      total (CT; cells/mm3) and differential leukocyte counts (mononuclear - MON, and
      polymorphonuclear - PMN, cells/mm3) of the articular inflammatory exudate. The
      variable exercise protocol inhibited incapacitation and edema for both joints.
      However, cell migration decreased only in the TF.The constant exercise reduced
      edema in both joints, and cell migration was decreased in the TT. However, the
      incapacitation was not reduced. Variable exercise seemed to be more effective in
      reducing the inflammatory parameters than constant exercise.

PMID- 24878854
TI  - Study of self-medication for musculoskeletal pain among nursing and medicine
      students at Pontificia Universidade Catolica - Sao Paulo.
AB  - OBJECTIVE: To study the self-medication for pain among students of medicine and
      nursing of the PUCSP compared with students from other knowledge areas. MATERIAL
      AND METHODS: Data were obtained in two groups: A - students from the health
      knowledge area, and B - students of law and engineering. It was used a
      questionnaire developed by the authors. Statistical analysis used the Chi-square
      test and the Fischer. RESULTS: In relation to gender, there is a predominance of
      women in the health group and a male majority in other one. In the health group
      there was a greater number of medical students, and in the control group of
      engineering. It is observed a high degree of selftreatment in both groups. It
      appears that participants in the health group have used more anti-inflammatory
      drugs and opioid than the others subjects studied. CONCLUSION: The frequency of
      medication for pain is higher in the group of health students, and self
      medication is equally practiced among students of health and other areas.

PMID- 24878855
TI  - Translation, cultural adaptation and validation into portuguese (Brazil) in
      Systemic Sclerosis Questionnaire (SySQ).
AB  - INTRODUCTION: Systemic sclerosis (SSc) is a multisystem disease, autoimmune
      disorder characterized by a fibroblastic disfunction, with significant impact on
      quality of life (QoL), measured by instruments or questionnaires that usually
      were formulated in other languages and in different cultural contexts. OBJECTIVE:
      Translate into Brazilian Portuguese, cross cultural adaptation and assess the
      reliability and validity of the Systemic Sclerosis Questionnaire (SySQ).
      METHODOLOGY: Translation and adaptation: into Portuguese and cross-cultural
      adaptation was performed in accordance with studies on questionnaire translation
      methodology into other languages. Reliability: it was analyzed using three
      interviews with different interviewers, two on the same day (interobserver) and
      the third within 14 days of the first assessment (intraobserver).Validity was
      assessed by correlating clinical and quality of life parameters with the domain
      scores of Sysc. STATISTICAL ANALYSIS: a descriptive analysis of the study sample.
      Reproducibility was assessed using an intraclass correlation coefficient (ICC).
      Internal consistency was assessed using Cronbach's alpha coefficient. To assess
      validity we used Spearman correlation coefficient. Five percent was the level of
      significance adopted for all statistical tests. RESULTS: In the evaluation of the
      questionnaires, the results were similar to the original questionnaire, the
      internal consistency ranging between 0.73 and 0.93 for each item. The
      interobserver reproducibility was very good for all domains (alpha = 0.786 to
      0.983) and intraobserver agreement was considered very good for general symptoms
      domain (ICC = 0.916), good for musculoskeletal symptoms domain (ICC = 0.897) and
      cardiopulmonary domain (ICC = 0.842) and reasonable for gastrointestinal symptoms
      domain (ICC = 0.686). CONCLUSION: The Brazilian Portuguese version of SySQ proved
      to be reproducible and valid for our population, using a recognized methodology
      for translation and cultural adaptation of questionnaires, as well as to assess
      the reproducibility and validity.

PMID- 24878856
TI  - Immediate infusional reactions to intravenous immunobiological agents for the
      treatment of autoimmune diseases: experience of 2126 procedures in a non
      oncologic infusion centre.
AB  - INTRODUCTION: With the increasing use of immunobiological drugs (IBD), the
      knowledge about their effectiveness and safety has increased. OBJECTIVE: To
      analyze the immediate infusional reactions (IIR) to intravenous IBD: infliximab
      (IFX), rituximab (RTX), abatacept (ABT) and tocilizumab (TCZ) on the treatment of
      autoimmune diseases. METHOD: 2126 infusions performed in the Infusion Centre -
      CID in 268 patients were analyzed. The used drug, its clinical indication,
      infusion time, and use of premedication were determined by the prescribing
      physician. All intercurrences presented during infusion and/or during a thirty
      minutes observation period were considered as IIR. The approach adopted in IIR
      followed the protocols of the Infusion Centre - CID. RESULTS: Regarding the type
      of IBD, the infused drugs given were: IFX (1584, 74.5%), TCZ (226, 10.63%), RTX
      (185, 8.7%) and ABT (131, 6,16%). IIR were described in 87 procedures (9.4%): 77 
      IFX group and 10 - RTX group. IIR were not described in ABT and TCZ groups. Most
      were considered as mild (n = 5; 41.17%) or moderate (n = 50, 58.81%) reactions;
      there were no serious reactions. Regarding to discontinue infusions, 79 (92.9%)
      were resumed and completed successfully. Only six (0.28% of infusions) were not
      completed because of IIR. CONCLUSION: Despite the differences between the number
      of procedures per drug, ours is a "real life" analysis, where the incidence of
      IIR was similar to that described in the literature. The low incidence of IIR
      corroborates the safety data, both quantitatively and qualitatively, and
      underscores the importance of specialized medical support during infusion.

PMID- 24878857
TI  - Is swimming able to maintain bone health and to minimize postmenopausal bone
      resorption?
AB  - OBJECTIVE: We studied the effect of swimming on the somatic and bone growth of
      female rats. METHODS: 40 neonate Wistar female rats were separated into:
      monosodium glutamate group (GluM, n = 20) and received MSG solution (4.0 mg/g) on
      alternate days during the first 14 days after birth, and Saline group (SAL, n =
      20) which received saline solution for the same period of time and at the same
      dose.At 60 days of age, GluM group was ovariectomized (GluMO) and SAL group just
      suffered surgical stress. Subsequently, half the animals in each group started
      swimming, resulting in groups: sedentary saline (SALsed, n = 10), swimming saline
      (SALswi, n = 10), sedentary ovariectomized Glutamate (GluMOsed, n = 10) and
      swimming ovariectomized Glutamate (GluMOswi, n = 10). At the end of the
      experiment, we measured the animals' longitudinal length and weight; their radius
      was weighed and its length measured. RESULTS: The animals of the GluMOsed group
      had lower body weight and longitudinal length compared to SALsed. Swimming
      decreased body weight, but had no influence on the longitudinal length of the
      GluMOswi group compared to GluMOsed group. Longitudinal length and body weight
      were lower in SALswi animals compared to SALsed animals. Radius weight and length
      of GluMOsed animals were lower than in SALsed animals. There was no difference in
      these parameters between GluMOsed and GluMOswi groups; however, these parameters
      were lower in SALswi animals compared to SALsed animals. CONCLUSION: Swimming
      does not influence previously affected bone tissue during the neonatal period,
      however it may cause damage to healthy bone tissue.

PMID- 24878858
TI  - Protocol for physical assessment in patients with fibromyalgia syndrome.
AB  - INTRODUCTION: Fibromyalgia syndrome (FMS) is a chronic disease that causes pain
      and fatigue, presenting a negative impact on quality of life. Exercise helps
      maintaining physical fitness and influences directly on the improvement of
      quality of life. OBJECTIVE: Develop a protocol for health-related physical
      fitness assessment of patients with FMS with tests that are feasible and
      appropriate for this population. METHOD: An exploratory and analytical literature
      review was performed, seeking to determine the tests used by the scientific
      community. With this in mind, we performed a literature revision through the use
      of virtual libraries databases: PubMed, Bireme, Banco de Teses e Dissertacoes da
      Capes and Biblioteca Digital Brasileira de Teses e Dissertacoes, published in
      between 1992-2012. RESULTS: A variety of tests was found; the following, by
      number of citations, stood out: Body Mass Index (BMI) and bioimpedance; 6-minute
      walk; handgrip strength (dynamometer, 1RM [Repetition Maximum]); Sit and reach
      and Shoulder flexibility; Foot Up and Go, and Flamingo balance. CONCLUSION: These
      are the tests that should make up the protocol for the physical evaluation of FMS
      patients, emphasizing their ease of use.

PMID- 24878859
TI  - Periodontitis exposure within one year before anti-diabetic treatment and the
      risk of rheumatoid arthritis in diabetes mellitus patients: a population-based
      cohort study.
AB  - OBJECTIVE: To examine whether a history of periodontitis (PD) before anti
      diabetic treatment is associated with risk of rheumatoid arthritis (RA)
      development in newly-treated diabetes mellitus (DM) patients. METHODS: We
      conducted a population-based retrospective cohort study using the 1997-2009
      National Health Insurance (NHI) claims data of one million representative
      individuals from all NHI enrollees. Adults with DM (aged >= 20 years) starting
      anti-diabetic treatment during 2001-2009 were classified as newly-treated DM
      patients. We identified 7097 DM subjects with PD history within one year before
      initiating anti-diabetes treatment (index date). By matching these 7097 subjects
      for age on the index date, sex, and year of the index date, we randomly extracted
      14,194 DM subjects without PD history within one year before antidiabetic
      treatment. Adjusted hazard ratios (aHRs) with a 95% confidence interval (CI) were
      calculated by applying Cox proportional hazards models to quantify the
      association between PD history and RA risk. RESULTS: Compared with DM patients
      without PD exposure within one year before anti-diabetic treatment, crude HR and
      adjusted HR of RA among DM patients with PD exposure within one year before anti
      diabetic treatment were 4.51 (95% CI, 1.39-14.64) and 3.77 (95% CI, 1.48-9.60).
      CONCLUSION: PD exposure within one year before anti-diabetic treatment was
      associated with increased RA risk in newly treated DM patients. The lack of
      knowledge about individual smoking status is a major limitation of this study.

PMID- 24878860
TI  - Incidence of neoplasms in the most prevalent autoimmune rheumatic diseases: a
      systematic review.
AB  - This article is a systematic review of the literature about the coexistence of
      cancer and autoimmune rheumatic diseases, their main associations, cancers and
      possible risk factors associated, with emphasis on existing population-based
      studies, besides checking the relation of this occur with the use of the drugs
      used in the treatment of autoimmune diseases. A search was conducted of
      scientific articles indexed in the Cochrane / BVS, Pubmed / Medline and Scielo /
      Lilacs in the period from 2002 to 2012. Also consulted was the IB-ICT (Brazilian
      digital library of theses and Masters), with descriptors in Portuguese and
      English for "Systemic sclerosis", "Rheumatoid Arthritis", " Systemic Lupus
      Erythematosus" and "Sjogren's syndrome", correlating each one with the descriptor
      AND "neoplasms". The results showed that in the database IBICT a thesis and a
      dissertation for the descriptor SLE met the inclusion criteria, none met RA one
      thesis to SS. Lilacs in the database/Scielo found two articles on "Rheumatoid
      Arthritis" AND "neoplasms". In Pubmed/Medline the inicial search resulted in 118
      articles, and 41 were selected. The review noted the relationship between cancer
      and autoimmune rheumatic diseases, as well as a risk factor for protection,
      although the pathophysiological mechanisms are not known. 

PMID- 24878862
TI  - Chronic lymphomonocytic meningoencephalitis, oligoarthritis and erythema nodosum:
      report of Baggio-Yoshinari syndrome of long and relapsing evolution.
AB  - The Brazilian human borreliosis, also known as Baggio-Yoshinari Syndrome (BYS),
      is a tickborne disease but whose ticks do not pertain to the Ixodes ricinus
      complex. It is caused by Borrelia burgdorferi sensu lato microorganisms and
      resembles clinical and laboratory features of Lyme disease (LD). BYS is also
      distinguished from LD by its prolonged clinical evolution, with relapsing
      episodes and autoimmune dysfunction. We describe the case of a young female who,
      over one year, progressively presented with oligoarthritis, cognitive impairment,
      menigoencephalitis and erythema nodosum. Diagnosis was established by means of
      the clinical history and a positive serology to Borrelia burgdorferi sensu
      strictu. The patient received Ceftriaxone 2 g IV/day during 30 days, followed by
      2 months of doxicycline 100 mg bid. Symptoms remitted and the Borrelia serology
      tests returned to normality. BYS is a new disease described only in Brazil, which
      has a raising frequency and deserves the attention from the country's medical
      board because of clinical, epidemiological and laboratory differences from LD.
      Despite the fact that it is a hard-to-diagnose zoonosis, it is important to
      pursuit an early diagnosis because the symptoms respond well to antibiotics or it
      might be resistant to treatment and may evolve to a chronic phase with both
      articular and neurological sequelae. 

PMID- 24878861
TI  - Evaluation protocols of hand grip strength in individuals with rheumatoid
      arthritis: a systematic review.
AB  - Hand grip strength is a useful measurement for individuals with rheumatoid
      arthritis, since this disease is often associated with functional anomalies of
      the hands and a consequent reduction in muscular strength. Thus, the
      standardization of the test protocol is important in relation to make
      reproducible and reliable studies. The aim of this systematic review was to
      verify the parameters associated with the measurement of the hand grip strength
      in individuals with rheumatoid arthritis. The review was carried out according to
      the recommendations of PRISMA, based on the databases of the Web of Science and
      the Journals Website of the Brazilian governmental agency CAPES. The following
      inclusion criteria were established: articles whose themes involved dynamometry
      to measure the hand grip in adult patients with rheumatoid arthritis, published
      in English between 1990 and 2012. The articles were selected by two independent
      reviewers. Initially, 628 articles were identified, and in the final review only
      40 were included in the qualitative synthesis, that is, those in which the main
      tool used to evaluate the hand grip strength was the Jamar(r). In relation to the
      hand grip strength parameters feedback type, hand dominance, repetitions,
      contraction intensity, acquisition time and rest period many data are imprecise
      and were not detailed in the method description. It is clear that there is a need
      for the standardization of a protocol which establishes the type of dynamometer
      and the parameters to be evaluated and also takes into consideration the clinical
      conditions of patients with rheumatoid arthritis. 

PMID- 24878863
TI  - Severe leukopenia in a rheumatoid arthritis patient treated with a
      methotrexate/leflunomide combination.
AB  - A rheumatoid arthritis patient was treated for two years with methotrexate and
      leflunomide combination therapy. The evolution was uneventful until she had
      clopidogrel, simvastatin, isosorbide, aspirin and omeprazole added to medication
      due to acute myocardial infarction. Four weeks after this, she was hospitalized
      with severe leukopenia. 

PMID- 24878864
TI  - Fatal cryptococcal meningitis in a juvenile lupus erythematosus patient.
AB  - Cryptococcosis is a fungal infection caused by Cryptococcus neoformans, generally
      associated with immunodeficiency and immunosuppressive agents, and it is rarely
      reported in systemic lupus erythematosus (SLE), particularly in juvenile SLE
      (JSLE). From January 1983 to June 2011, 5,604 patients were followed at our
      University Hospital and 283 (5%) of them met the American College of Rheumatology
      (ACR) classification criteria for SLE. Only one (0.35%) of our JSLE patients had
      cryptococcal meningitis and is described in this report. A 10-year old girl was
      diagnosed with JSLE. By the age of 15 years, she presented persistent headaches,
      nausea and vomiting for a 5 day period without fever, after a cave-exploring
      trip. At that moment, she was under 10 mg/day of prednisone, azathioprine and
      hydroxychloroquine. A lumbar puncture was performed and India ink preparation was
      positive for cryptococcosis, cerebrospinal fluid culture yielded Cryptococcus
      neoformans and serum cryptococcal antigen titer was 1:128. Azathioprine was
      suspended, and liposomal amphotericin B was introduced. Despite of treatment,
      after four days she developed amaurosis and fell into a coma. A computer
      tomography of the brain showed diffuse ischemic areas and nodules suggesting
      fungal infection. Four days later, she developed severe sepsis and vancomycin and
      meropenem were prescribed, nevertheless she died due to septic shock. In
      conclusion, cryptococcal meningitis is a rare and severe opportunistic infection
      in juvenile lupus population. This study reinforces the importance of an early
      diagnosis and prompt introduction of antifungal agents, especially in patients
      with history of contact with bird droppings. 

PMID- 24878869
TI  - A computational study of alternate SELEX.
AB  - Systematic evolution of ligands by exponential enrichment (SELEX) is a procedure
      for identifying nucleic acid (NA) molecules with affinities for specific target
      species, such as proteins, peptides, or small organic molecules. Here, we extend
      the work in Seo et al. (Bull Math Biol 72:1623-1665, 2010) (multiple-target SELEX
      or positive SELEX) and examine an alternate SELEX process with multiple targets
      by incorporating negative selection into a positive SELEX protocol. The alternate
      SELEX process is done iteratively by alternating several positive selection
      rounds with several negative selection rounds. At the end of each positive
      selection round, NAs are eluted from the bound product and amplified by
      polymerase chain reaction (PCR) to increase the size of the pool of NA species
      that bind preferentially to the given positive target vector. The enriched
      population of NAs is then exposed to the negative targets (undesired targets).
      The free NA species (instead of the bound NA species being eluted) are retained
      and amplified by PCR (negative selection). The goal is to minimize an enrichment
      of nonspecifically binding NAs against multiple targets. While positive selection
      alone results in a pool of NAs that bind tightly to a given target vector,
      negative selection results in the subset of the NAs that bind best to the
      nontarget vectors that are also present. By alternating the two processes, we
      eventually obtain a refined population of nucleic acids that bind to the desired
      target(s) with high "selectivity" and "specificity." In the present paper, we
      give formulations of the negative and alternate selection processes and define
      their efficiencies in a meaningful way. We study the asymptotic behavior of
      alternate SELEX system as a discrete-time dynamical system. To do this, we use
      the chemical potential to examine how alternate SELEX leads to the selection of
      NAs with more specific interactions when the ratio of the number of positive
      selection rounds to the number of negative selection rounds is fixed. Alternate
      SELEX is said to be globally asymptotically stable if, given the initial target
      vector and a fixed ratio, the distribution of the limiting NA fractions does not
      depend on the relative concentrations of the NAs in the initial pool (provided
      that all of the NA species are initially present in the initial pool). We state
      conditions on the matrix of NA-target affinities that determine when the
      alternate SELEX process is globally asymptotically stable in this sense and
      illustrate these results computationally. 

PMID- 24878871
TI  - Paediatric critical incident analysis: lessons learnt on analysis,
      recommendations and implementation.
AB  - The objectives of this study were to identify causal and contributing factors of
      serious patient safety incidents in a paediatric university hospital, to report
      on ensuing recommendations and to assess the extent of implementation of the
      recommendations. The possible causal and contributing factors identified in 17
      incidents were classified by a system devised by Vincent et al. Proposed
      recommendations were classified by the same system, and degrees of implementation
      were established. A median of 5 causal and contributing factors per incident were
      identified. Twenty-two percent of all factors were related to teamwork and 22 %
      to task factors. A median of 5 recommendations per analysis were formulated. Most
      recommendations were related to task factors (36 %). The time load of each
      analysis was a mean of 27 h. One third of the recommendations have been acted
      upon, mostly those related to task and team factors. CONCLUSION: Incident
      analysis is time-consuming but yields indispensable information on causal and
      contributing factors, presenting numerous opportunities for quality improvement.
      The value of these analyses could be improved by appointing responsibilities and
      setting up time frames for implementation. A bottom-up approach with managerial
      support appears to be a key to turning incident analysis and quality improvement
      into an ongoing process.

PMID- 24878870
TI  - Mid-term results of 17-mm St. Jude Medical Regent prosthetic valves in elder
      patients with small aortic annuli: comparison with 19-mm bioprosthetic valves.
AB  - This study was designed to compare the mid-term outcomes after aortic valve
      replacement (AVR) between 17-mm mechanical heart valves (MV) and 19-mm
      bioprosthetic valves (BV) in elderly patients with small aortic annuli. Between
      2000 and 2011, 127 consecutive patients (mean age 79 years; 87 % female)
      underwent AVR for aortic valve stenosis with a small aortic annulus. 19-mm BV (n
      = 67) was implanted. When the 19-mm BV did not fit the annulus, 17-mm St. Jude
      Medical Regent prosthetic mechanical valve (n = 60) was used instead of an aortic
      root-enlargement procedure. The follow-up rate was 94.0 % in the BV group, and
      98.5 % in the MV group. No significant differences in survival rate and valve
      related complications were found between the 2 groups. In-hospital mortality
      rates were 1.5 % (n = 1) in the BV group and 5.0 % (n = 3) in the MV group. Late
      mortality rates were 3.9 % per patient-years (p-y; n = 8) in the BV group, and
      6.0 % per p-y (n = 10) in the MV group. Five-year Kaplan-Meier survival rates
      were 62 % in the BV group, and 72 % in the MV group (log-rank P = 0.280). Freedom
      from major adverse valve-related stroke and cerebral bleeding events was 92.5 and
      98.5 % in the BV group, and 94.7 and 100 % in the MV group. AVR using 17-mm MV in
      elder patients with small aortic annuli provided equivalent mid-term clinical
      results to that with 19-mm BV. 

PMID- 24878872
TI  - Cell membrane tracker based on restriction of intramolecular rotation.
AB  - The fluorescence of tetraphenylethylene (TPE), an archetypal luminogen, is
      induced by restriction of intramolecular rotation (RIR). TPE was grafted with
      palmitic acid (PA) onto a hydrophilic peptide to yield a cell membrane tracker
      named TR4. TR4 was incorporated into liposomes, where it showed significant RIR
      characteristics. When cells were incubated with TR4, cytoplasmic membranes were
      specifically labeled. TR4 shows excellent photostability and low cytotoxicity. 

PMID- 24878873
TI  - Glycemic index: is it a predictor of metabolic and vascular disorders?
AB  - PURPOSE OF REVIEW: The role of glycemic index on metabolic and cardiovascular
      risk factors received considerable attention in light of the current increase in
      cardiometabolic disorders. We aimed to deal and identify the recently published
      prospective epidemiological studies as well as randomized controlled studies
      investigating the associations of metabolic and cardiovascular risk markers with
      dietary intake of carbohydrates and with measures of the induced glycemic index.
      The main prospective studies and meta-analysis grouping the recent prospective
      and clinical interventions are discussed. RECENT FINDINGS: Recently, during the
      last few years, evidence exists that high glycemic index/glycemic load diets
      contribute to risk of type 2 diabetes and cardiovascular disease. Additionally,
      low glycemic index/glycemic load diets were found to be effective in the
      treatment of cardiometabolic disorders. SUMMARY: The use of the low glycemic
      index notion in the dietary recommendations for children, adolescents and adults
      might play a role in the prevention, and or treatment, of metabolic diseases and
      their cardiovascular complications.

PMID- 24878874
TI  - The fat cell senescence hypothesis: a mechanism responsible for abrogating the
      resolution of inflammation in chronic disease.
AB  - PURPOSE OF REVIEW: Obesity is a chronic inflammatory disease in which the
      physiological resolution of inflammation is attenuated, leading to low-grade
      inflammation throughout the body. However, the heat shock response, which is a
      key component of the physiological response to resolve inflammation, is seriously
      hampered in adipose tissue and other metabolic organs (e.g. skeletal muscle,
      liver, pancreatic beta-cells) in metabolic diseases. In this review, we
      hypothesize that adipocyte metabolic stress triggers the onset of fat cell
      senescence, and companion senescence-associated secretory phenotype (SASP), and
      that such a scenario is responsible for attenuating the resolution of
      inflammation. RECENT FINDINGS: We shall discuss the role of the heat shock
      response in the context of the resolution of inflammation and the relevance of
      heat shock response blockade in chronic inflammatory diseases. Sirtuin-1 is
      responsible for the induction of heat shock transcription factor-1 mRNA
      expression and for the stabilization of heat shock transcription factor-1 in a
      high-profile activity state. However, adipose tissue-emanated SASP depress
      sirtuin-1 expression, leading adipocytes to a perpetual state of unresolved
      inflammation, due to a dampening of the heat shock response. SUMMARY: The advance
      of inflammasome-mediated SASP from adipose to other tissues promotes cellular
      senescence in many other cells of the organism, aggravating obesity-dependent
      chronic inflammation. Inducers of heat shock response (e.g. heat shock itself,
      physical exercise and calorie restriction) may efficiently interrupt this vicious
      cycle and are envisaged as the best and also the most economical treatment for
      obesity-related chronic diseases.

PMID- 24878875
TI  - Factors of tidal volume variation during augmented spontaneous ventilation in
      patients on extracorporeal carbon dioxide removal. A multivariate analysis.
AB  - BACKGROUND: Extracorporeal carbon dioxide removal (ECCO2-R) allows lung
      protective ventilation using lower tidal volumes (VT) in patients with acute
      respiratory failure. The dynamics of spontaneous ventilation under ECCO2-R has
      not been described previously. This retrospective multivariable analysis examines
      VT patterns and investigates the factors that influence VT, in particular sweep
      gas flow and blood flow through the artificial membrane. METHODS: We assessed VT,
      respiratory rate (RR), minute ventilation (MV), and levels of pressure support (0
      24 cm H2O), sweep gas flow (0-14 L/min) and blood flow through the membrane (0.8
      1.8 L/min) in 40 patients from the moment they were allowed to breathe
      spontaneously. Modest hypercapnia was accepted. RESULTS: Patients tolerated
      moderate hypercapnia well. In a generalized linear model the increase in sweep
      gas flow (P<0.001), a low PaCO2 (P=0.029), and an increased breathing frequency
      (P<0.001) were associated with lower VT. Neither blood flow through the membrane
      (P=0.351) nor the level of pressure support (P=0.595) influenced VT size.
      CONCLUSION: Higher sweep gas flow is associated with low VT in patients on
      extracorporeal lung assist and augmented spontaneous ventilation. Such a
      technique can be used for prolonged lung protective ventilation even in the
      patient's recovery period.

PMID- 24878876
TI  - Sepsis-induced immunoparalysis: mechanisms, markers, and treatment options.
AB  - Sepsis remains the leading cause of death in the ICU. Considering the key role of
      the immune system in sepsis, immunomodulation represents an attractive target for
      adjunctive therapy. Until recently, clinical trials focused on suppression of the
      immune system, but this approach failed to improve sepsis outcome. Recent
      advances in the understanding of sepsis have led to the view that not the initial
      hyperinflammatory state, but rather a profoundly suppressed state of the immune
      system, called sepsis-induced immunoparalysis, accounts for the majority of
      sepsis-related deaths. Immunoparalysis results in ineffective clearance of septic
      foci, and renders the septic patient more vulnerable to secondary infections, as
      well as reactivation of latent infections. Several mechanisms behind
      immunoparalysis have been recognised. Furthermore, due to recognition of the
      importance of immunoparalysis, immunostimulatory treatment is emerging as a
      possible adjunctive treatment for sepsis. As such, identification of patients
      suffering from immunoparalysis using biomarkers is of utmost importance to guide
      immunostimulatory treatment. In this review, an short overview of the concept of
      immunoparalysis is presented, while the main focus is on potential biological
      markers of immunoparalysis and promising immunostimulatory therapeutic agents.
      The challenging heterogeneity of septic patients in respect to immunomodulatory
      advances will be discussed, and recommendations for future research are provided.

PMID- 24878877
TI  - When the duration of infusion does matter: the case of meropenem and
      piperacillin.

PMID- 24878878
TI  - The principal toxic glycosidic steroids in Cerbera manghas L. seeds:
      identification of cerberin, neriifolin, tanghinin and deacetyltanghinin by UHPLC
      HRMS/MS, quantification by UHPLC-PDA-MS.
AB  - The toxicity of the sea mango (Cerbera manghas L.) is well known. The plant is
      ranked as one of the deadliest of the southern Asian coastline. Cardenolidic
      heterosides are responsible for the cardiotoxicity of trees of the Cerbera genus.
      We have identified and determined the concentration of the principal glycosidic
      steroids present in the seeds of sea mangos (Thailand). Drug screening of an
      extract of the seeds was carried out using ultra-high performance liquid
      chromatography coupled to photodiode array detection and mass spectrometry (UHPLC
      PDA-MS) with quantification at 219nm. Identification was confirmed by UHPLC-HRMS.
      Deacetyltanghinin (m/z 549.3055+/-2ppm), neriifolin (m/z 535.3259+/-2ppm),
      tanghinin (m/z 591.3169+/-2ppm) and cerberin (577.3375+/-2ppm) were the most
      abundant glycosidic steroids present in the sea mango seeds. A seed of the dried
      ripe fruit had concentrations of 1209.1, 804.2, 621.4 and 285.9MUg/g,
      respectively. A seed of the fresh unripe fruit had concentrations of 49.4, 47.0,
      3.5 and 2.3MUg/g. 

PMID- 24878880
TI  - 400 MBq of 18F-FDG: one size no longer fits all?

PMID- 24878879
TI  - Quantification of folate metabolites in serum using ultraperformance liquid
      chromatography tandem mass spectrometry.
AB  - Folate deficiency is considered a risk factor for many diseases such as cancer,
      congenital heart disease and neural tube defects (NTDs). There is a pressing need
      for more methods of detecting folate and its main metabolites in the human body.
      Here, we developed a simple, fast and sensitive ultraperformance liquid
      chromatography tandem mass spectrometry (UPLC/MS/MS) method for the simultaneous
      quantifications of folate metabolites including folic acid, 5
      methyltetrahydrofolate (5-MeTHF), 5-formyltetrahydrofolate (5-FoTHF),
      homocysteine (Hcy), S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH).
      The method was validated by determining the linearity (r(2)>0.998), sensitivity
      (limit of detection ranged from 0.05 to 0.200ng/mL), intra- and inter-day
      precision (both CV<6%) and recovery (each analyte was >90%). The total analysis
      time was 7min. Serum samples of NTD-affected pregnancies and controls from a NTD
      high-risk area in China were analyzed by this method, the NTD serum samples
      showed lower concentrations of 5-MeTHF (P<0.05) and 5-FoTHF (P<0.05), and higher
      concentrations of Hcy (P<0.05) and SAH (P<0.05) compared with serum samples from
      controls, consistent with a previous study. These results showed that the method
      is sensitive and reliable for simultaneous determination of six metabolites,
      which might indicate potential risk factors for NTDs, aid early diagnosis and
      provide more insights into the pathogenesis of NTDs. 

PMID- 24878881
TI  - SPECT/CT for the assessment of painful knee prosthesis.

PMID- 24878882
TI  - Painful knee prosthesis: is there a role for bone SPECT/CT?

PMID- 24878883
TI  - Considerations on absence of 68Ga-DOTA-F(ab')2-trastuzumab tracer uptake in HER2
      overexpressing tumor lesions.

PMID- 24878884
TI  - Response to the letter from Oude Munnink et al.

PMID- 24878886
TI  - Acupressure in insomnia and other sleep disorders in elderly institutionalized
      patients suffering from Alzheimer's disease.
AB  - BACKGROUND: Sleep disorders are very common in elderly institutionalized people
      with dementia and acupressure recently has been associated with conventional
      medicine in their treatment. AIMS: Exploring the effectiveness of acupressure for
      the treatment of insomnia and other sleep disturbances and we want to show that
      the acupressure treatment is feasible also in elderly resident patients. METHODS:
      We enrolled institutionalized patients suffering from Alzheimer's disease with
      mild cognitive impairment and insomnia. A daily acupressure on HT7 point (H7
      Insomnia Control((r))) was performed for a 8-week period. We administered the
      following scales: the mini mental state examination, the global deterioration
      scale, the neuropsychiatric inventory, the state-trait-anxiety inventory, the
      activity daily living and the instrumental activity daily living, the global
      health quality of life, and the Pittsburgh sleep quality index. RESULTS: After
      receiving the acupressure treatment, patients saw a significant decrease of sleep
      disorders. The number of hours of effective sleep was perceived as increased.
      Furthermore, the time necessary to fall asleep decreased significantly and also
      the quality of sleep increased. Additionally, also the quality of life was
      bettered. Sedative drugs have been reduced in all patients involved in the study.
      CONCLUSIONS: Acupressure can be recommended as a complementary, effective, and
      non-intrusive method to reduce sleep disturbances in old resident patients
      affected by cognitive disorders. A limitation of the study is the small sample
      size. More studies are needed to further validate the results of our study.

PMID- 24878887
TI  - Clinical practice guideline for dedicated breast PET.

PMID- 24878888
TI  - Nuclear myocardial perfusion imaging with a cadmium-telluride semiconductor
      detector gamma camera in patients with acute myocardial infarction.
AB  - OBJECTIVE: Since myocardial perfusion imaging (MPI) with conventional sodium
      iodine (NaI) device has low spatial resolution, there have been some cases in
      which small structures such as non-transmural myocardial infarction could not be
      properly detected. The purpose of this study was to evaluate potential usefulness
      of cadmium-telluride (CdTe) semiconductor detector-based high spatial resolution
      gamma cameras in detecting myocardial infarction sites, especially non-transmural
      infarction. METHODS: A total of 38 patients (mean age +/- SD: 64 +/- 21 year) who
      were clinically diagnosed with acute myocardial infarction were included. Twenty
      eight cases of them were with ST segment elevation myocardial infarction (STEMI)
      and 10 cases with non-ST segment elevation myocardial infarction (NSTEMI). In all
      patients, myocardial perfusion single photon emission computed tomography images
      were acquired with Infinia (NaI device) and R1-M (CdTe device), and the images
      were compared concerning the detectability of acute myocardial infarction sites.
      RESULTS: The detection rates of the myocardial infarction site in cases with
      STEMI were 100% both by NaI and CdTe images. In cases with NSTEMI, detection rate
      by NaI images was 50%, while that of CdTe images was 100% (p = 0.033). The summed
      rest score (SRS) value derived from CdTe images was significantly higher than
      that from NaI images in cases with STEMI [NaI images: 12 (7-18) versus CdTe
      images: 14 (9-20)] (p < 0.001). SRS derived from CdTe images was significantly
      higher than that derived from NaI images in cases with NSTEMI [NaI images: 2 (0
      5) versus CdTe images: 6 (6-8)] (p = 0.006). CONCLUSIONS: These results indicate
      that MPI using CdTe-semiconductor device will provide a much more accurate
      assessment of acute myocardial infarction in comparison to current methods.

PMID- 24878889
TI  - Optimized dendritic cell-based immunotherapy for melanoma: the TriMix-formula.
AB  - Since decades, the main goal of tumor immunologists has been to increase the
      capacity of the immune system to mediate tumor regression. In this regard, one of
      the major focuses of cancer immunotherapy has been the design of vaccines
      promoting strong tumor-specific cytotoxic T lymphocyte responses in cancer
      patients. Here, dendritic cells (DCs) play a pivotal role as they are regarded as
      nature's adjuvant and as such have become the natural agents for antigen delivery
      in order to finally elicit strong T cell responses (Villadangos and Schnorrer in
      Nat Rev Immunol 7:543-555, 2007; Melief in Immunity 29:372-383, 2008; Palucka and
      Banchereau in Nat Rev Cancer 12:265-277, 2012; Vacchelli et al. in Oncoimmunology
      2:e25771, 2013; Galluzzi et al. in Oncoimmunology 1:1111-1134, 2012). Therefore,
      many investigators are actively pursuing the use of DCs as an efficient way of
      inducing anticancer immune responses. Nowadays, DCs can be generated at a large
      scale in closed systems, yielding sufficient numbers of cells for clinical
      application. In addition, with the identification of tumor-associated antigens,
      which are either selectively or preferentially expressed by tumors, a whole range
      of strategies using DCs for immunotherapy have been designed and tested in
      clinical studies. Despite the evidence that DCs loaded with tumor-associated
      antigens can elicit immune responses in vivo, clinical responses remained
      disappointingly low. Therefore, optimization of the cellular product and route of
      administration was urgently needed. Here, we review the path we have followed in
      the development of TriMixDC-MEL, a potent DC-based cellular therapy, discussing
      its development as well as further modifications and applications. 

PMID- 24878891
TI  - Reconciling the deep homology of neuromodulation with the evolution of behavior.
AB  - The evolution of behavior seems inconsistent with the deep homology of
      neuromodulatory signaling. G protein coupled receptors (GPCRs) evolved slowly
      from a common ancestor through a process involving gene duplication,
      neofunctionalization, and loss. Neuropeptides co-evolved with their receptors and
      exhibit many conserved functions. Furthermore, brain areas are highly conserved
      with suggestions of deep anatomical homology between arthropods and vertebrates.
      Yet, behavior evolved more rapidly; even members of the same genus or species can
      differ in heritable behavior. The solution to the paradox involves changes in the
      compartmentalization, or subfunctionalization, of neuromodulation; neurons shift
      their expression of GPCRs and the content of monoamines and neuropeptides.
      Furthermore, parallel evolution of neuromodulatory signaling systems suggests a
      route for repeated evolution of similar behaviors. 

PMID- 24878890
TI  - Combination of an agonistic anti-CD40 monoclonal antibody and the COX-2 inhibitor
      celecoxib induces anti-glioma effects by promotion of type-1 immunity in myeloid
      cells and T-cells.
AB  - Malignant gliomas are heavily infiltrated by immature myeloid cells that mediate
      immunosuppression. Agonistic CD40 monoclonal antibody (mAb) has been shown to
      activate myeloid cells and promote antitumor immunity. Our previous study has
      also demonstrated blockade of cyclooxygenase-2 (COX-2) reduces immunosuppressive
      myeloid cells, thereby suppressing glioma development in mice. We therefore
      hypothesized that a combinatory strategy to modulate myeloid cells via two
      distinct pathways, i.e., CD40/CD40L stimulation and COX-2 blockade, would enhance
      anti-glioma immunity. We used three different mouse glioma models to evaluate
      therapeutic effects and underlying mechanisms of a combination regimen with an
      agonist CD40 mAb and the COX-2 inhibitor celecoxib. Treatment of glioma-bearing
      mice with the combination therapy significantly prolonged survival compared with
      either anti-CD40 mAb or celecoxib alone. The combination regimen promoted
      maturation of CD11b(+) cells in both spleen and brain, and enhanced Cxcl10 while
      suppressing Arg1 in CD11b(+)Gr-1(+) cells in the brain. Anti-glioma activity of
      the combination regimen was T-cell dependent because depletion of CD4(+) and
      CD8(+) cells in vivo abrogated the anti-glioma effects. Furthermore, the
      combination therapy significantly increased the frequency of CD8(+) T-cells,
      enhanced IFN-gamma-production and reduced CD4(+)CD25(+)Foxp3(+) T regulatory
      cells in the brain, and induced tumor-antigen-specific T-cell responses in lymph
      nodes. Our findings suggest that the combination therapy of anti-CD40 mAb with
      celecoxib enhances anti-glioma activities via promotion of type-1 immunity both
      in myeloid cells and T-cells. 

PMID- 24878892
TI  - Electro-cortical manifestations of common vs. proper name processing during
      reading.
AB  - The main purpose of the present study was to investigate how proper and common
      nouns are represented in the brain independent of memory retrieval processes.
      Participants were instructed to perform a lexical decision task while dense-array
      EEG was continuously recorded. Both ERP components (namely N400 and P300) and
      swLORETA suggested that proper name processing engaged a more widespread neural
      network and required more cognitive resources than common noun processing.
      Overall, our results come down in favor of the hypothesis that specific effects
      of proper vs. common noun processing exist, and they suggest a possible neuro
      functional segregation of proper vs. common noun processing. The difference in
      proper and common noun processing seems to emerge at the level of storage or
      representation of lexical knowledge, and it may crucially depend on their
      semantic characteristics. 

PMID- 24878893
TI  - Isoquinoline-derivatized tris(2-pyridylmethyl)amines as fluorescent zinc sensors
      with strict Zn2+/Cd2+ selectivity.
AB  - Tris(2-pyridylmethyl)amine-based fluorescent ligands, N,N-bis(1
      isoquinolylmethyl)-2-pyridylmethylamine (1-isoBQPA) and N,N-bis(7-methoxy-1
      isoquinolylmethyl)-2-pyridylmethylamine (7-MeO-1-isoBQPA), have been prepared and
      the Zn(2+)-induced fluorescence enhancement has been investigated. Upon
      excitation at 324 nm, 1-isoBQPA exhibits a very weak emission (phi = ~0.010) in
      DMF-H2O (1 : 1). Upon Zn(2+) addition, the 1-isoBQPA fluorescence increases
      (phi(Zn) = 0.055) at 357 nm and 464 nm. The fluorescence enhancement at longer
      wavelengths is Zn(2+)-specific, whereas Cd(2+) induces a small emission increase
      at 464 nm (I(Cd)/I0 = 1.1, I(Cd)/I(Zn) = 14%). The Zn(2+)/Cd(2+) selectivity of
      the fluorescent response correlates with the Cd-N(isoquinoline) and Zn
      N(isoquinoline) bond distances measured in the crystal structures. Introduction
      of methoxy groups into the 1-isoBQPA chromophore enhances the fluorescence
      significantly (phi(Zn) = 0.213), which affords 7-MeO-1-isoBQPA properties
      amenable for fluorescence microscopy in living cells.

PMID- 24878894
TI  - Motor abnormalities and basal ganglia in schizophrenia: evidence from structural
      magnetic resonance imaging.
AB  - At the beginning of the twentieth century, many authors proposed that a
      considerable number of schizophrenic patients experience genuine motor
      abnormalities (GMA). In the era of antipsychotic treatment, GMA became a
      scientifically and clinically challenging characteristic of schizophrenia. Over
      the past 10 years, several magnetic resonance imaging (MRI) studies suggested a
      crucial role of the motor system in this disorder. Constituting a major relay
      center in the extrapyramidal motor system and being involved in the automatic
      execution of motor plans, an involvement of the basal ganglia with GMA and
      schizophrenia is plausible. However, the precise morphological correlates of GMA
      have remained controversial. The aim of this paper is to systematically review
      structural neuroimaging findings on GMA and basal ganglia in individuals with
      schizophrenia. Nineteen structural MRI studies were identified for inclusion in
      the review. Considering the extant data, there is some evidence for volumetric
      and shape alterations of basal ganglia in schizophrenia being in part determined
      by psychopathology and GMA, and not entirely explained by antipsychotic
      medication effects. 

PMID- 24878895
TI  - Effect of changes in stimulus site on activation of the posterior parietal
      cortex.
AB  - A previous functional magnetic resonance imaging study elucidated the specific
      activity of the inferior parietal lobe (IPL) during a two-point discrimination
      task compared with that during an intensity discrimination task Akatsuka et al.
      (Neuroimage 40: 852-858, 2008). If the posterior parietal cortex (PPC), including
      IPL, is responsible for detecting changes in stimulus sites, PPC activity depends
      on the level of change at stimulus sites. The aim of this study was to clarify
      whether a particular site exists that could detect changes in stimulus sites
      using the oddball paradigm. Somatosensory-evoked magnetic fields were recorded in
      10 right-handed subjects. Three oddball conditions were performed by all
      subjects, with the probability of deviant and standard stimuli being 20 and 80 %,
      respectively, under all three conditions. Deviant stimuli were always presented
      to the second digit of the hand and standard stimuli were presented to the first
      (small deviance: SD) and fifth digits (medium deviance: MD) of the hand and the
      first digit of the toe (large deviance: LD). Inter-stimulus intervals were set at
      500 ms. A brain electrical source analysis showed that activities of areas 1 and
      3b elicited by the deviant stimuli were not significantly different among the
      three conditions. In contrast, PPC activity was significantly greater for LD than
      for SD and MD. PPC activity tended to increase with greater deviance at stimulus
      sites, but activities of areas 1 and 3b did not differ. These findings suggest
      that PPC may have a functional role in automatic change detection systems with
      regard to deviance of stimulus sites. 

PMID- 24878896
TI  - Adolescent civic engagement and adult outcomes: an examination among urban racial
      minorities.
AB  - Civic engagement in adolescence is encouraged because it is hypothesized to
      promote better civic, social, and behavioral outcomes. However, few studies have
      examined the effects of civic engagement on youth development over time. In
      particular, the long-term association between adolescent civic engagement and
      development among racial minority youth who are exposed to high levels of risk
      factors is understudied. Using data from the Chicago Longitudinal Study (CLS; N =
      854; 56.6 % were female; 93 % were African Americans and 7 % were Latinos), this
      study examined the associations between civic engagement in adolescence and
      outcomes during emerging adulthood among racial minority youth. Regression
      analyses found that civic engagement in adolescence is related to higher life
      satisfaction, civic participation, and educational attainment, and is related to
      lower rates of arrest in emerging adulthood. The findings suggest that adolescent
      civic engagement is most impactful in affecting civic and educational outcomes in
      emerging adulthood. The present study contributes to the literature by providing
      support for the long-term associations between adolescent civic engagement and
      multiple developmental domains in adulthood among an inner-city minority cohort. 

PMID- 24878897
TI  - Death certificates underestimate infections as proximal causes of death in the
      U.S.
AB  - BACKGROUND: Death certificates are a primary data source for assessing the
      population burden of diseases; however, there are concerns regarding their
      accuracy. Diagnosis-Related Group (DRG) coding of a terminal hospitalization may
      provide an alternative view. We analyzed the rate and patterns of disagreement
      between death certificate data and hospital claims for patients who died during
      an inpatient hospitalization. METHODS: We studied respondents from the Health and
      Retirement Study (a nationally representative sample of older Americans who had
      an inpatient death documented in the linked Medicare claims from 1993-2007).
      Causes of death abstracted from death certificates were aggregated to the
      standard National Center for Health Statistics List of 50 Rankable Causes of
      Death. Centers for Medicare and Medicaid Services (CMS)-DRGs were manually
      aggregated into a parallel classification. We then compared the two systems via
      2*2, focusing on concordance. Our primary analysis was agreement between the two
      data sources, assessed with percentages and Cohen's kappa statistic. RESULTS:
      2074 inpatient deaths were included in our analysis. 36.6% of death certificate
      cause-of-death codes agreed with the reason for the terminal hospitalization in
      the Medicare claims at the broad category level; when re-classifying DRGs without
      clear alignment as agreements, the concordance only increased to 61%. Overall
      Kappa was 0.21, or "fair." Death certificates in this cohort redemonstrated the
      conventional top 3 causes of death as diseases of the heart, malignancy, and
      cerebrovascular disease. However, hospitalization claims data showed infections,
      diseases of the heart, and cerebrovascular disease as the most common diagnoses
      for the same terminal hospitalizations. CONCLUSION: There are significant
      differences between Medicare claims and death certificate data in assigning cause
      of death for inpatients. The importance of infections as proximal causes of death
      is underestimated by current death certificate-based strategies.

PMID- 24878899
TI  - [Bacterial resistance collaborative group. Much more than 10 years history].

PMID- 24878898
TI  - A novel herbal medicine, KIOM-C, induces autophagic and apoptotic cell death
      mediated by activation of JNK and reactive oxygen species in HT1080 human
      fibrosarcoma cells.
AB  - KIOM-C was recently demonstrated to have anti-metastatic activity in highly
      malignant cancer cells via suppression of NF-kappaB-mediated MMP-9 activity. In
      addition, it was reported to be effective for clearance of the influenza virus by
      increasing production of anti-viral cytokines, such as TNF-alpha and IFN-gamma,
      and efficacious in the treatment of pigs suffering from porcine circovirus
      associated disease (PCVAD). In this study, we investigated whether KIOM-C induces
      cancer cell death and elucidated the underlying anti-cancer mechanisms. In
      addition, we examined whether KIOM-C oral administration suppresses in vivo tumor
      growth of HT1080 cells in athymic nude mice. We initially found that KIOM-C at
      concentrations of 500 and 1000 ug/ml caused dose- and time-dependent cell death
      in cancer cells, but not normal hepatocytes, to approximately 50% of control
      levels. At the early stage of KIOM-C treatment (12 h), cells were arrested in G1
      phase, which was accompanied by up-regulation of p21 and p27, down-regulation of
      cyclin D1, and subsequent increases in apoptotic and autophagic cells. Following
      KIOM-C treatment, the extent of caspase-3 activation, PARP cleavage, Beclin-1
      expression, and LC3-II conversion was remarkably up-regulated, but p62 expression
      was down-regulated. Phosphorylation of AMPK, ULK, JNK, c-jun, and p53 was
      increased significantly in response to KIOM-C treatment. The levels of
      intracellular ROS and CHOP expression were also increased. In particular, the JNK
      specific inhibitor SP600125 blocked KIOM-C-induced ROS generation and CHOP
      expression almost completely, which consequently almost completely rescued cell
      death, indicating that JNK activation plays a critical role in KIOM-C-induced
      cell death. Furthermore, daily oral administration of 85 and 170 mg/kg KIOM-C
      efficiently suppressed the tumorigenic growth of HT1080 cells, without systemic
      toxicity. These results collectively suggest that KIOM-C efficiently induces
      cancer cell death by both autophagy and apoptosis via activation of JNK signaling
      pathways, and KIOM-C represents a safe and potent herbal therapy for treating
      malignancies. 

PMID- 24878901
TI  - [Monitoring of activity of influenza in Santa Fe, Argentina, 2005-2010].
AB  - BACKGROUND: Influenza viruses have a relevant public health impact. OBJECTIVE: To
      describe the activity of influenza and assess the morbidity and mortality impact
      during 2005 to 2010 in Santa Fe, Argentina. METHODS: Epidemiological and
      virological indicators were calculated based on sentinel surveillance. Mortality
      data from patients over and under the age of 65 were analyzed using the
      integrated autoregressive moving average model and an excess of mortality
      attributable to influenza was determined. RESULTS: The viral circulation effect
      on morbidity was measured through the evolution in the proportion of influenza
      like illness (ILI) patients. Peak incidence was observed between weeks 23 and 33.
      An excess of deaths was identified in 2007 among patients over 65 and among those
      under 65 in 2009, which was related with influenza A(H3N2) and A(H1N1)pandemic
      virus circulation respectively, associated with a higher proportion of virus
      recovery and a higher ILI percentage. CONCLUSIONS: The sentinel surveillance of
      influenza is a simple and efficient methodology that identifies influenza trends.
      Our study showed that the virus has caused a rise of mortality in patients > 65
      in epidemic periods associated with the H3N2 subtype and in patients < 65 in the
      pandemic period with the circulation ofA(HIN1)pandemic virus.

PMID- 24878900
TI  - [Antimicrobial susceptibility in Chile 2012].
AB  - Bacteria antimicrobial resistance is an uncontrolled public health problem that
      progressively increases its magnitude and complexity. The Grupo Colaborativo de
      Resistencia, formed by a join of experts that represent 39 Chilean health
      institutions has been concerned with bacteria antimicrobial susceptibility in our
      country since 2008. In this document we present in vitro bacterial susceptibility
      accumulated during year 2012 belonging to 28 national health institutions that
      represent about 36% of hospital discharges in Chile. We consider of major
      importance to report periodically bacteria susceptibility so to keep the medical
      community updated to achieve target the empirical antimicrobial therapies and the
      control measures and prevention of the dissemination of multiresistant strains.

PMID- 24878902
TI  - [Pneumonia in the inmunocompromised host: perspective through images diagnosis
      and a Bayesian inference].
AB  - INTRODUCTION: The population of immunocompromised patients has increased in
      recent decades. Many of these patients eventually present infectious
      complications including pneumonia, which is a diagnostic that must to be prompt
      and accurate. OBJECTIVE: To review the basis of the diagnosis of pneumonia in the
      immunocompromised patient. Sorted by the methodology of Bayesian inference, very
      relevant in the diagnostic attribution, we review the main basis of the diagnosis
      of pneumonia of immunocompromised patients: the epidemiology, the clinical
      history including the type of immunosuppression that weigh the likelihood of
      attribution a priori of an etiologic agent, and finally, the findings in the
      image (or likelihood function). CONCLUSION: Although in general the findings are
      not pathognomonic and there is much overlap in the images, there are several
      features that orient in one direction or another. Proper assessment of the prior
      probability and the likelihood function is allowing ultimately a good diagnostic
      proposition.

PMID- 24878903
TI  - [Early detection of cytomegalovirus infection in allogeneic hematopoietic stem
      cell transplant patients by real time-quantitative PCR].
AB  - INTRODUCTION: CMV pp65-antigenemia (antigenemia) has been used for monitoring CMV
      viremia in allogeneic hematopoietic stem cell transplant (aHSCT) recipients.
      Recently, real time quantitative PCR (RT-qPCR) has been used as a better approach
      than antigenemia for CMV diagnosis. The objective of this study was to assess the
      correlation of CMV viremia between RT-qPCR and antigenemia in aHSCT patients.
      MATERIAL AND METHODS: Observational prospective study of all aHSCT patients
      during 10 months in our center. CMV RT-qPCR in whole blood was performed weekly
      from day +7 to +100 after aHSCT. Simultaneous antigenemia was performed from
      engrafment to day +100. Concordance between both assays was evaluated. RESULTS:
      Eighteen patients were included. In 120 simultaneous samples, 96 were concordant
      by both methods (80%). Kappa coefficient was 0.583. In 42% of cases without
      concordant results, patients were on antiviral therapy. Thirteen patients (72%)
      developed CMV infection (20 episodes). In 17 episodes, both the antigenemia and
      CMV RT-qPCR were positive. CMV RT-qPCR was detectable 1-2 weeks before
      antigenemia in 45% of the episodes. CONCLUSION: Both methods had a moderate
      concordance and CMV RT-qPCR detects CMV reactivations earlier than antigenemia,
      especially in neutropenic patients.

PMID- 24878904
TI  - [Concordance of nasal swabs and nasopharyngeal swabs in the detection of
      respiratory viruses by direct immunofluorescence].
AB  - BACKGROUND: The most used test for the diagnosis of viral respiratory infection
      is the detection of viral antigens by direct immunofluorescence (DFA), in samples
      taken by nasopharyngeal swab (NPS) or aspirate (NPA). It would be desirable to
      have a less uncomfortable technique to obtain a sample from the patient, but of
      equal performance. AIM: To evaluate the diagnostic agreement between nasal swab
      (NS) and nasopharyngeal swab (NPS) in the detection of respiratory viruses by DFA
      and compare the degree of discomfort of both techniques in pediatric patients.
      METHODOLOGY: Cross-sectional study in children who consulted to a pediatric
      emergency service with respiratory symptoms. Two samples (NPS and NS) per child
      were collected. The concordance between the two was determined by Kappa (K)
      coefficient and the degree of discomfort by a visual pain scale. RESULTS: We
      obtained 112 samples from 56 children, one by each technique. 82.1% were
      concordant, K = 0.61 (CI 95%, 0.39-0.83) for the detection of any virus, and K =
      0.69 (CI 95%, 0.46-0.92) and K = 0.76 (CI 95%, 0.51-1) for syncytial respiratory
      virus and influenza A detection, respectively. The degree of discomfort was
      significantly lower for the NS. CONCLUSION: There is considerable agreement in
      the detection of respiratory viruses by DFA between samples obtained by NS and
      NPS, but not enough to recommend a change in the sampling method in this
      population.

PMID- 24878905
TI  - [Antimicrobial susceptibility and polyclonal dissemination of Staphylococcus
      aureus strains].
AB  - OBJECTIVES: To determine the prevalence ofmethicillin-resistant Staphylococcus
      aureus (MRSA), its antimicrobial susceptibility patterns and classify strains by
      pulsed-field gel electrophoresis (PFGE). MATERIAL AND METHODS: 106 S. aureus
      strains isolated from patients hospitalized at the Maracaibo city university
      hospital, Venezuela, were processed during the first quarter of 2009. The
      culture, isolation and identification of S. aureus were done by conventional
      methods. Antimicrobial susceptibility was determined by the disk diffusion
      method. The presence of mecA gene in MRSA strains was verified using the
      polymerase chain reaction (PCR). RESULTS: Fifty-four strains (50.94%) were MRSA
      and twenty three antibiotypes were detected. The most frequently observed was the
      one including beta-lactams, macrolides, lincosamides, aminoglycosides and
      quinolones. There were forty multi-resistant isolates (74.0%) between MRSA
      strains. All methicillin-resistant isolates were mecA positive. PFGE classified
      MRSA stains in 50 pulsotypes, each one containing between six and thirteen bands.
      Four small groups, of two strains each, had 80% of similarity. Five of the eight
      strains in these small clusters (62.50%) had the same pattern of resistance.
      CONCLUSION: There is a high prevalence of multi-resistant MRSA strains with
      polyclonal dissemination in the hospital.

PMID- 24878906
TI  - [Laboratory guidelines for diagnosis of invasive fungal disease caused by
      filamentous fungi].
AB  - Early diagnosis and timely treatment are critical in Invasive Fungal Disease
      (IFD) caused by filamentous fungi in immunocompromised patients. Clinical
      features of IFD are nonspecific; therefore, images (CT scan), direct microscopic
      examination, staining and cultures of clinical samples and galactomannan
      determination in blood or BAL, are substantial. This guideline provides
      recommendations on transport and sample processing, including stains and culture
      media requirements. It also describes clues for diagnosis of major genera and
      species of Aspergillus.

PMID- 24878907
TI  - [Infections in patients affected by rheumatologic diseases associated to
      glucocorticoid use or tumor necrosis factor-alpha inhibitors].
AB  - A great diversity of infectious agents can affect patients that use steroids at
      immunosuppressive doses or tumor necrosis factor alpha (TNF-alpha) antagonists.
      The list of participating microorganisms is more restricted in the case of anti
      TNF-alpha blockers. Overlapping agents include intracellular bacteria,
      Mycobacterium tuberculosis, geographic fungal agents that have the ability to
      establish granulamotous infections, herpes zoster, and reactivation of chronic
      hepatitis B virus infection. An important conceptual issue for these infections
      is the existence of a threshold prednisone daily dose for the emergence of
      opportunistic infections but higher levels of immunosuppression and cofactors are
      required in the case of Pneumocystis jiroveci and cytomegalovirus infections. In
      order to prevent these threats, a detailed medical evaluation is needed before
      prescription to detect potential risks and manage them properly. Prevention rules
      must be prescribed in every case, that include common sense behaviors, vaccines,
      and in selected cases, chemoprophylaxis for latent tuberculosis (TB) infection,
      P. jiroveci pneumonia (PCP) or other specific requirements. Latent TB infection
      is probable and requires chemoprophylaxis in the case of remote or recent
      exposure to a patient with lung TB, a positive tuberculin or interferon-gamma
      release assay result or residual lung scars in a chest x-ray exam. PCP prevention
      is suggested when the patient reaches a daily dose of prednisone of 30 mg but
      might be needed at lower doses in case of other concomitant immunosuppressive
      drugs or when lymphopenia arises shortly after prednisone initiation.

PMID- 24878908
TI  - [Cancer of cervix in Chile. Too much vaccine amid a neglected Papanicolau].
AB  - The Chilean Ministry of Health announced the incorporation of a human
      papillomavirus (HPV) vaccine to prevent cervix uterine cancer (CUC) into the
      national immunization program during year 2014 This decision was adopted despite
      of two opposing documents and a significant decrease in cervical cancer
      associated mortality due to cytological cervical screening. The burden of disease
      attributed to CUC has declined in Chile and current cost-effectiveness studies
      should be reviewed considering this decreasing trend, the progressive decrease in
      coverage rates observed during the past years, the potential need for aditional
      doses and lower vaccine costs if vaccine is acquired through the PAHO revolving
      fund. Moreover, serious adverse events associated with these vaccines, which in
      some countries are more frequent than CUC associated mortality, have not been
      thoroughly evaluated and are probably underreported. The decision to incorporate
      the vaccine occurs in a context of progressive weakening of the national cervical
      screening program leading to a reduced population coverage. This situation
      jepeordizes the achievements already obtained and poses a challenge to vaccine
      introduction considering that not all the high-risk viral subtypes are included
      and thus the risk for CUC does not disappear making cervical screening a vital
      component of the program that needs to be maintained. This governmental
      resolution requires a more solid scientific foundation and should not be
      implemented without resolving current cervical screening shortcomings.

PMID- 24878909
TI  - [Strategy for the prevention of papillomavirus related diseases. Substantiation
      of a programmatic decision in Chile].

PMID- 24878910
TI  - [Recommendations for Chilean travelers to the FIFA World Cup 2014 in Brazil].
AB  - This article provides a checklist of precautions and vaccines for Chilean
      travelers attending the FIFA World Cup 2014 in Brazil. It aims to help physicians
      to prepare visitors of this mass gathering and summarizes useful hints to avoid
      infectious diseases considering the circumstances and availabilities in Chile.

PMID- 24878912
TI  - [Conjunctival rhinosporidiois diagnosed in a biopsy specimen].
AB  - 11 years old girl, from south region of Chile, without history of travels outside
      Chile nor the province, complaints of red eye with blepharitis and blood-tingued
      epiphora. Eye exam revealed a pseudomembrane. Clinical diagnosis was folicular
      conjunctivitis. A surgical removal was performed and the lesion sent to biopsy
      analysis. On microscopic examination numerous 50-150 microm cysts with keratinous
      wall and numerous endospores were found. Rinosporidiosis is an infection caused
      by Rhinosporidium seeberi that frecuently affects nasal cavity but could infect
      eye, urogenital tract and airways. This infections is considered endemic in Asia
      and Africa, but it is very important to have the suspicious among polyps in these
      areas because travel to endemic areas is become more frecuently.

PMID- 24878913
TI  - [From pirates to virus: the Oropesa's journey].
AB  - In 1902, being Chile a country free of yellow fever, the British steamship
      Oropesa arrived from Rio de Janeiro with three passengers suffering this disease.
      Captain Hayes rejected the quarantine imposed by the local Junta of Sanity in
      Punta Arenas and also in Coronel, following his journey with the sick passengers
      to Valparaiso, port where he accepted a brief quarantine and medical services for
      the most compromised of the three patients, who unfortunately died. The knowledge
      about yellow fever and the applicable epidemiological measures in that time in
      Chile come to us through the sessions of the Superior Council of Public Hygiene.
      The threat that implicated the presence of the Oropesa in Chilean coasts is
      compared with the arrival of British pirates and corsairs in the colonial
      centuries, before the independence, announced with the alarm cry charque (for
      Sharp) is coming to Coquimbo!

PMID- 24878915
TI  - [Probiotic effects on late-onset sepsis in very preterm infants.]

PMID- 24878914
TI  - [Esophageal aspergillosis in a patient with acute myelogenous leukemia and
      febrile neutropenia].
AB  - Aspergillosis usually compromises the respiratory system, but can also affect
      others. We report a 46 yo female with acute myeloid leukemia, developed febrile
      neutropenia and dysphagia. Endoscopy revealed esophageal cytomegalovirus-like
      ulcers, but biopsies showed Aspergillus spp. It's important to consider
      aspergillosis in the differential diagnosis of esophageal lesions in high-risk
      patients.

PMID- 24878916
TI  - [Automated versus manual sample inoculations in routine clinical microbiology.]

PMID- 24878917
TI  - [Contamination of healthcare workers hands with Clostridium difficile Spores
      after caring for patients with C. difficile Infection.]

PMID- 24878918
TI  - Screening of Neisseria gonorrhoeae and Chlamydia trachomatis by self collected
      vaginal sample.

PMID- 24878919
TI  - R. S. WebTool, a web server for random sampling-based significance evaluation of
      pairwise distances.
AB  - Pairwise comparison of data vectors represents a large part of computational
      biology, especially with the continuous increase in genome-wide approaches
      yielding more information from more biological samples simultaneously. Gene
      clustering for function prediction as well as analyses of signalling pathways and
      the time-dependent dynamics of a system are common biological approaches that
      often rely on large dataset comparison. Different metrics can be used to evaluate
      the similarity between entities to be compared, such as correlation coefficients
      and distances. While the latter offers a more flexible way of measuring potential
      biological relationships between datasets, the significance of any given distance
      is highly dependent on the dataset and cannot be easily determined. Monte Carlo
      methods are robust approaches for evaluating the significance of distance values
      by multiple random permutations of the dataset followed by distance calculation.
      We have developed R. S. WebTool (http://rswebtool.kwaklab.org), a user-friendly
      online server for random sampling-based evaluation of distance significances that
      features an array of visualization and analysis tools to help non
      bioinformaticist users extract significant relationships from random noise in
      distance-based dataset analyses. 

PMID- 24878920
TI  - ChIP-Enrich: gene set enrichment testing for ChIP-seq data.
AB  - Gene set enrichment testing can enhance the biological interpretation of ChIP-seq
      data. Here, we develop a method, ChIP-Enrich, for this analysis which empirically
      adjusts for gene locus length (the length of the gene body and its surrounding
      non-coding sequence). Adjustment for gene locus length is necessary because it is
      often positively associated with the presence of one or more peaks and because
      many biologically defined gene sets have an excess of genes with longer or
      shorter gene locus lengths. Unlike alternative methods, ChIP-Enrich can account
      for the wide range of gene locus length-to-peak presence relationships (observed
      in ENCODE ChIP-seq data sets). We show that ChIP-Enrich has a well-calibrated
      type I error rate using permuted ENCODE ChIP-seq data sets; in contrast, two
      commonly used gene set enrichment methods, Fisher's exact test and the binomial
      test implemented in Genomic Regions Enrichment of Annotations Tool (GREAT), can
      have highly inflated type I error rates and biases in ranking. We identify DNA
      binding proteins, including CTCF, JunD and glucocorticoid receptor alpha
      (GRalpha), that show different enrichment patterns for peaks closer to versus
      further from transcription start sites. We also identify known and potential new
      biological functions of GRalpha. ChIP-Enrich is available as a web interface
      (http://chip-enrich.med.umich.edu) and Bioconductor package. 

PMID- 24878921
TI  - Unique subunit packing in mycobacterial nanoRNase leads to alternate substrate
      recognitions in DHH phosphodiesterases.
AB  - DHH superfamily includes RecJ, nanoRNases (NrnA), cyclic nucleotide
      phosphodiesterases and pyrophosphatases. In this study, we have carried out in
      vitro and in vivo investigations on the bifunctional NrnA-homolog from
      Mycobacterium smegmatis, MSMEG_2630. The crystal structure of MSMEG_2630 was
      determined to 2.2-A resolution and reveals a dimer consisting of two identical
      subunits with each subunit folding into an N-terminal DHH domain and a C-terminal
      DHHA1 domain. The overall structure and fold of the individual domains is similar
      to other members of DHH superfamily. However, MSMEG_2630 exhibits a distinct
      quaternary structure in contrast to other DHH phosphodiesterases. This novel mode
      of subunit packing and variations in the linker region that enlarge the domain
      interface are responsible for alternate recognitions of substrates in the
      bifunctional nanoRNases. MSMEG_2630 exhibits bifunctional 3'-5' exonuclease [on
      both deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) substrates] as well
      as CysQ-like phosphatase activity (on pAp) in vitro with a preference for nanoRNA
      substrates over single-stranded DNA of equivalent lengths. A transposon
      disruption of MSMEG_2630 in M. smegmatis causes growth impairment in the presence
      of various DNA-damaging agents. Further phylogenetic analysis and genome
      organization reveals clustering of bacterial nanoRNases into two distinct
      subfamilies with possible role in transcriptional and translational events during
      stress. 

PMID- 24878922
TI  - Decision-making during NHEJ: a network of interactions in human PolMU implicated
      in substrate recognition and end-bridging.
AB  - Human PolMU is a DNA polymerase belonging to the X family that has been
      implicated in the non-homologous end-joining (NHEJ) pathway during repair of
      double-strand breaks in DNA. Loop1 is a flexible piece of PolMU which has a
      critical role during terminal transferase and end-joining activities: it acts as
      a pseudo-template when the template strand is discontinuous or unavailable,
      whilst diffusing away if present to avoid steric clashes. Mutational analysis and
      inspection of the 3D structures available allowed us to identify a network of
      residues in charge of sensing the presence or absence of discontinuities in the
      template strand, which will in turn determine the final position adopted by
      Loop1. This network is formed by the previously uncharacterized thumb mini-loop
      (NSH motif) and the positively charged helix N, which contribute to the correct
      positioning of Loop1 and to juxtapose the discontinuous template strand during
      NHEJ of incompatible ends. Accordingly, single mutation of specific conserved
      residues in these motifs, whilst irrelevant in most of the cases for gap filling,
      largely affected terminal transferase and end-joining activities. Other point
      mutations in the 'hinges' of Loop1, such as residues Phe385 or Phe389,
      corroborated the flexibility requirements of this motif.

PMID- 24878923
TI  - Silencing of IFN-stimulated gene transcription is regulated by histone H1 and its
      chaperone TAF-I.
AB  - Chromatin structure and its alteration play critical roles in the regulation of
      transcription. However, the transcriptional silencing mechanism with regard to
      the chromatin structure at an unstimulated state of the interferon (IFN)
      stimulated gene (ISG) remains unclear. Here we investigated the role of template
      activating factor-I (TAF-I, also known as SET) in ISG transcription. Knockdown
      (KD) of TAF-I increased ISG transcript and simultaneously reduced the histone H1
      level on the ISG promoters during the early stages of transcription after IFN
      stimulation from the unstimulated state. The transcription factor levels on the
      ISG promoters were increased in TAF-I KD cells only during the early stages of
      transcription. Furthermore, histone H1 KD also increased ISG transcript. TAF-I
      and histone H1 double KD did not show the additive effect in ISG transcription,
      suggesting that TAF-I and histone H1 may act on the same regulatory pathway to
      control ISG transcription. In addition, TAF-I KD and histone H1 KD affected the
      chromatin structure near the ISG promoters. On the basis of these findings, we
      propose that TAF-I and its target histone H1 are key regulators of the chromatin
      structure at the ISG promoter to maintain the silent state of ISG transcription. 

PMID- 24878925
TI  - SuperPred: update on drug classification and target prediction.
AB  - The SuperPred web server connects chemical similarity of drug-like compounds with
      molecular targets and the therapeutic approach based on the similar property
      principle. Since the first release of this server, the number of known compound
      target interactions has increased from 7000 to 665,000, which allows not only a
      better prediction quality but also the estimation of a confidence. Apart from the
      addition of quantitative binding data and the statistical consideration of the
      similarity distribution in all drug classes, new approaches were implemented to
      improve the target prediction. The 3D similarity as well as the occurrence of
      fragments and the concordance of physico-chemical properties is also taken into
      account. In addition, the effect of different fingerprints on the prediction was
      examined. The retrospective prediction of a drug class (ATC code of the WHO)
      allows the evaluation of methods and descriptors for a well-characterized set of
      approved drugs. The prediction is improved by 7.5% to a total accuracy of 75.1%.
      For query compounds with sufficient structural similarity, the web server allows
      prognoses about the medical indication area of novel compounds and to find new
      leads for known targets. SuperPred is publicly available without registration at:
      http://prediction.charite.de.

PMID- 24878926
TI  - Clinical course and outcomes of Iranian children with juvenile dermatomyositis
      and polymyositis.
AB  - This study evaluated the clinical features, course, and outcomes of Iranian
      children with juvenile dermatomyositis (JDM), juvenile polymyositis (JPM), and
      other uncommon connective tissue disorders. A chart review of 85 Iranian children
      with JDM and JPM was performed during a 10-year period from 2003 to 2013. The
      patients' clinical signs and symptoms, laboratory data, and other factors
      affecting clinical outcomes were recorded using questionnaires. Statistical
      analysis was performed using SPSS software version 20. In all, 40 boys and 45
      girls were included in the study (F/M, 1.1:1). Disease frequency was
      significantly higher in boys aged <5 years (F/M, 0.4:1) and girls aged >5 years
      (F/M, 1.6:1). The combined mean age at diagnosis was 7.5 years. Muscle weakness,
      particularly in the proximal muscles of lower extremities (96 %); fatigue (83 %);
      and heliotrope rash (71 %) were the most frequently recorded symptoms. Elevated
      lactate dehydrogenase level was the most common enzyme disturbance (98 %).
      Monocyclic course was seen in 60 % of patients. The mean treatment duration was 3
      years. The incidence rate of complications such as calcinosis, lipodystrophy, and
      growth disturbances was 20, 9, and 30 %, respectively. The occurrence of these
      complications in patients with monocyclic disease was significantly lower. Vital
      organ involvement led to the death of four patients. The incidence of calcinosis
      was significantly lower in patients having a shorter interval between disease
      onset and treatment. Two important complications, failure to thrive and
      lipodystrophy, were significantly higher in patients having antinuclear
      antibodies. The incidence of the above three complications was higher in patients
      with polycyclic or continuous chronic disease. Respiratory failure was the most
      common cause of patient mortality. 

PMID- 24878930
TI  - Moving Narcissus: Can Narcissists Be Empathic?
AB  - Empathy plays a critical role in fostering and maintaining social relations.
      Narcissists lack empathy, and this may account for their interpersonal failures.
      But why do narcissists lack empathy? Are they incapable, or is change possible?
      Three studies addressed this question. Study 1 showed that the link between
      narcissism and low empathy generalizes to a specific target person presented in a
      vignette. The effect was driven by maladaptive narcissistic components (i.e.,
      entitlement, exploitativeness, exhibitionism). Study 2 examined the effect of
      perspective-taking (vs. control) instructions on self-reported responses to a
      video. Study 3 examined the effect of the same manipulation on autonomic arousal
      (heart rate [HR]) during an audio-recording. Perspective-taking ameliorated
      negative links between maladaptive narcissism and both self-reported empathy and
      HR. That is, narcissists can be moved by another's suffering, if they take that
      person's perspective. The findings demonstrate that narcissists' low empathy does
      not reflect inability, implying potential for intervention.

PMID- 24878927
TI  - Diminished ovarian reserve in Behcet's disease patients.
AB  - This study aims to assess ovarian reserve markers in Behcet's disease (BD)
      patients. Ten BD and 22 healthy controls were evaluated for ovarian reserve by
      examining the levels of follicle-stimulating hormone (FSH), luteinizing hormone
      (LH), estradiol, inhibin B, total morning testosterone, prolactin, thyroid
      stimulating hormone (TSH), and antral follicle count. Anti-Mullerian hormone
      (AMH) was measured using two different enzyme-linked immunosorbent assay (ELISA)
      kits. Demographic data, menstrual abnormalities, disease parameters, and
      treatments were also analyzed. The median current age was similar in BD patients
      and controls (34 (20-40) vs. 31.3 (20-42) years, p = 0.33). A positive
      correlation was observed between the AMH Gen II ELISA and AMH/MISAnshLabs ELISA
      assays in the BD patients (r = +0.98; p < 0.0001) and healthy controls (r =
      +0.93; p < 0.0001). The mean AMH by Gen II (0.93 +/- 0.8 vs. 2.59 +/- 1.8 ng/mL,
      p = 0.01) and AMH/MIS AnshLabs ELISA (1.07 +/- 0.86 vs. 2.51 +/- 1.8 ng/mL, p =
      0.02) were significantly reduced in the BD patients versus controls. A trend of
      decreased AMH (<1.0 ng/mL) was observed in BD patients compared to that in the
      controls (50 vs. 19 %, p = 0.09) using either kits. The mean FSH was
      significantly higher in the BD patients compared to that in the controls (9.1 +/-
      3.6 vs. 6.5 +/- 2.7, p = 0.04). No differences were found for the other ovarian
      parameters in both groups (p > 0.05). Current disease activity was only observed
      in BD patients with a low AMH level; however, there was no statistical
      significance (40 vs. 0 %, p = 0.44). Cyclophosphamide use was reported in only
      one patient with a low AMH and high FSH level. The present study was the first to
      suggest that BD patients may have diminished ovarian reserve. The contribution of
      disease activity remains to be determined. 

PMID- 24878928
TI  - Hurricane activity and the large-scale pattern of spread of an invasive plant
      species.
AB  - Disturbances are a primary facilitator of the growth and spread of invasive
      species. However, the effects of large-scale disturbances, such as hurricanes and
      tropical storms, on the broad geographic patterns of invasive species growth and
      spread have not been investigated. We used historical aerial imagery to determine
      the growth rate of invasive Phragmites australis patches in wetlands along the
      Atlantic and Gulf Coasts of the United States. These were relatively undisturbed
      wetlands where P. australis had room for unrestricted growth. Over the past
      several decades, invasive P. australis stands expanded in size by 6-35% per year.
      Based on tropical storm and hurricane activity over that same time period, we
      found that the frequency of hurricane-force winds explained 81% of the variation
      in P. australis growth over this broad geographic range. The expansion of P.
      australis stands was strongly and positively correlated with hurricane frequency.
      In light of the many climatic models that predict an increase in the frequency
      and intensity of hurricanes over the next century, these results suggest a strong
      link between climate change and species invasion and a challenging future ahead
      for the management of invasive species. 

PMID- 24878929
TI  - Analysis of Phaseolus vulgaris response to its association with Trichoderma
      harzianum (ALL-42) in the presence or absence of the phytopathogenic fungi
      Rhizoctonia solani and Fusarium solani.
AB  - The present study was carried out to evaluate the ability of Trichoderma
      harzianum (ALL 42-isolated from Brazilian Cerrado soil) to promote common bean
      growth and to modulate its metabolism and defense response in the presence or
      absence of the phytopathogenic fungi Rhizoctonia solani and Fusarium solani using
      a proteomic approach. T. harzianum was able to promote common bean plants growth
      as shown by the increase in root/foliar areas and by size in comparison to plants
      grown in its absence. The interaction was shown to modulate the expression of
      defense-related genes (Glu1, pod3 and lox1) in roots of P. vulgaris. Proteomic
      maps constructed using roots and leaves of plants challenged or unchallenged by
      T. harzianum and phytopathogenic fungi showed differences. Reference gels
      presented differences in spot distribution (absence/presence) and relative
      volumes of common spots (up or down-regulation). Differential spots were
      identified by peptide fingerprinting MALDI-TOF mass spectrometry. A total of 48
      identified spots (19 for leaves and 29 for roots) were grouped into protein
      functional classes. For leaves, 33%, 22% and 11% of the identified proteins were
      categorized as pertaining to the groups: metabolism, defense response and
      oxidative stress response, respectively. For roots, 17.2%, 24.1% and 10.3% of the
      identified proteins were categorized as pertaining to the groups: metabolism,
      defense response and oxidative stress response, respectively. 

PMID- 24878931
TI  - The prognostic significance of the prognostic nutritional index in cancer: a
      systematic review and meta-analysis.
AB  - PURPOSE: The prognostic nutritional index (PNI) is a simple and effective
      parameter, initially created to evaluate preoperative nutritional conditions and
      surgical risk. It has been recently been found to be associated with short- and
      long-term outcomes of various malignancies. We performed a meta-analysis to
      determine the predictive significance of PNI in cancer, as a mean to assist in
      determining the optimal surgery timing and in improving the survival of cancer
      patients. METHODS: Data were retrieved from PubMed and ISI Web of Science to
      identify eligible studies. Odds ratios (ORs) and hazard ratios (HRs) were
      extracted and pooled to explore the relationships of PNI with patient survival
      and clinicopathological features. RESULTS: Fourteen studies with a total of 3,414
      participants met the inclusion criteria. Low PNI was associated with poor overall
      survival (pooled OR 1.80, 95 % confidence interval [CI] 1.59-2.04) and the
      presence of post-operative complications (pooled OR 2.45, 95 % CI 1.31-4.58) in
      cancer patients, but not with cancer-specific survival (CSS) (pooled HR 1.81, 95
      % CI 0.94-3.49). PNI was also found to be associated with invasion depth (pooled
      OR 5.07, 95 % CI 2.34-10.96) and lymph node metastasis (pooled OR 3.70, 95 % CI
      2.32-5.92) in gastric cancer, whereas TNM stage was the only clinicopathological
      feature associated with PNI in colorectal carcinoma (pooled OR 1.81, 95 % CI 1.24
      2.64). CONCLUSIONS: PNI might be an effective predictive indicator for the
      prognosis of cancer, especially digestive system carcinomas. Further studies are
      required to verify the significance of PNI in clinical practice.

PMID- 24878933
TI  - A paradigm shift towards quality of kidney transplantation in Iran.

PMID- 24878934
TI  - Is joint hypermobility associated with vesicoureteral reflux?

PMID- 24878932
TI  - Prognosis in human glioblastoma based on expression of ligand growth hormone
      releasing hormone, pituitary-type growth hormone-releasing hormone receptor, its
      splicing variant receptors, EGF receptor and PTEN genes.
AB  - PURPOSE: Glioblastoma (GB) is the most frequent brain tumor. Despite recent
      improvement in therapeutic strategies, the prognosis of GB remains poor. Growth
      hormone-releasing hormone (GHRH) may act as a growth factor; antagonists of GHRH
      have been successfully applied for experimental treatment of different types of
      tumors. The expression profile of GHRH receptor, its main splice variant SV1 and
      GHRH have not been investigated in human GB tissue samples. METHODS: We examined
      the expression of GHRH, full-length pituitary-type GHRH receptor (pGHRHR), its
      functional splice variant SV1 and non-functional SV2 by RT-PCR in 23 human GB
      specimens. Epidermal growth factor receptor (EGFR) and phosphatase and tensin
      homolog gene (PTEN) expression levels were also evaluated by quantitative RT-PCR.
      Correlations between clinico-pathological parameters and gene expressions were
      analyzed. RESULTS: Expression of GHRH was found to be positive in 61.9 % of
      samples. pGHRH receptor was not expressed in our sample set, while SV1 could be
      detected in 17.4 % and SV2 in 8.6 % of the GB tissues. In 65.2 and 78.3 % of
      samples, significant EGFR over-expression or PTEN under-representation could be
      detected, respectively. In 47.8 % of cases, EGFR up-regulation and PTEN down
      regulation occurred together. Survival was significantly poorer in tumors lacking
      GHRH expression. This worse prognosis in GHRH negative group remained significant
      even if SV1 was also expressed. CONCLUSION: Our study shows that GHRH and SV1
      genes expressed in human GB samples and their expression patterns are associated
      with poorer prognosis.

PMID- 24878935
TI  - Echocardiography evaluation and exercise in hemodialysis patients.

PMID- 24878936
TI  - Factors associated with survival of kidney allografts.

PMID- 24878924
TI  - Type II restriction endonucleases--a historical perspective and more.
AB  - This article continues the series of Surveys and Summaries on restriction
      endonucleases (REases) begun this year in Nucleic Acids Research. Here we discuss
      'Type II' REases, the kind used for DNA analysis and cloning. We focus on their
      biochemistry: what they are, what they do, and how they do it. Type II REases are
      produced by prokaryotes to combat bacteriophages. With extreme accuracy, each
      recognizes a particular sequence in double-stranded DNA and cleaves at a fixed
      position within or nearby. The discoveries of these enzymes in the 1970s, and of
      the uses to which they could be put, have since impacted every corner of the life
      sciences. They became the enabling tools of molecular biology, genetics and
      biotechnology, and made analysis at the most fundamental levels routine. Hundreds
      of different REases have been discovered and are available commercially. Their
      genes have been cloned, sequenced and overexpressed. Most have been characterized
      to some extent, but few have been studied in depth. Here, we describe the
      original discoveries in this field, and the properties of the first Type II
      REases investigated. We discuss the mechanisms of sequence recognition and
      catalysis, and the varied oligomeric modes in which Type II REases act. We
      describe the surprising heterogeneity revealed by comparisons of their sequences
      and structures. 

PMID- 24878937
TI  - Recurrent cytomegalovirus infection: prevalence and risk factors.

PMID- 24878938
TI  - An update on pathogenesis of systemic lupus erythematosus.
AB  - Systemic lupus erythematosus is a group of diseases that seem to become separate
      entities by etiology in the near future. Its pathogenesis remains elusive;
      however, multifactorial interactions among genetic and environmental factors may
      be involved. Systemic lupus erythematosus is the perfect prototype of autoimmune
      disorder with multiple derangements, starting from innate immunity to adaptive
      immune system leading to loss of self-tolerance. An overview of the pathogenesis
      of systemic lupus erythematosus is the focus of this review. 

PMID- 24878939
TI  - Outlook of organ transplantation in Iran: time for quality assessment.
AB  - Organ transplantation as an undeniable life-saving therapeutic modality
      fundamentally requires infrastructure, devoted and trained professionals, and
      positive public attitude to be set up in a well-organized manner at the national
      level. In addition to sharing achievements and reviewing the increasing trend of
      transplanted organs in the past 12 years following legislations in Iran, this
      report raises some concerns from the point of transplantation outcome view. 

PMID- 24878940
TI  - Relationship of generalized joint hypermobility with vesicoureteral reflux and
      urinary tract infection.
AB  - INTRODUCTION: Generalized joint hypermobility is deemed to be an underlying risk
      factor for many clinical conditions. The goal of this study was to determine the
      prevalence of generalized joint hypermobility in patients with vesicoureteral
      reflux. MATERIALS AND METHODS: This was a cross-sectional study on 313 children,
      3 to 15 years old, with a history of urinary tract infection. Generalized joint
      hypermobility was evaluated according to the Beighton scores. Urinary tract
      ultrasonography and cystography were done if indicated. Participants were divided
      into 2 groups, group 1 without urinary tract abnormality and group 2 with primary
      vesicoureteral reflux, which were compared with the control group. RESULTS:
      Generalized joint hypermobility was documented in 37.2% of the children in the
      control group and 45.7% of those in group 1. This rate was 62.3% in group 2 (odds
      ratio, 2.79; 95% confidence interval, 1.61 to 4.82). Generalized joint
      hypermobility was seen in 44.1% of the children with mild vesicoureteral reflux,
      60.5% of those with moderate vesicoureteral reflux, and 86.2% of those with
      severe vesicoureteral reflux. There was a significant relationship between the
      hypermobility incidence and the urinary reflux severity (P = .003). CONCLUSIONS:
      This study showed the prevalence of generalized joint hypermobility in children
      with vesicoureteral reflux was more than that in the general population, and the
      prevalence of hypermobility syndrome increased with the reflux severity.

PMID- 24878941
TI  - Regulatory effects of chronic low-dose morphine on nitric oxide level along with
      baroreflex sensitivity in two-kidney one-clip hypertensive rats.
AB  - INTRODUCTION: Opiates are traditionally used for treatment of some acute heart
      disorders. There are only few reports on the effects of long-term treatment of
      cardiovascular diseases with morphine. This study aimed to investigate the
      effects of chronic low-dose morphine use on the cardiovascular system in two
      kidney one-clip (2K1C) hypertensive rats. MATERIALS AND METHODS: Male Wistar rats
      were divided into two groups as the sham and 2K1C groups and each group was
      further subdivided into saline and morphine treatment subgroups. Blood pressure,
      heart rate, plasma rennin activity, serum nitric oxide concentration, and
      baroreflex sensitivity were measured. RESULTS: Morphine significantly attenuated
      systolic blood pressure, diastolic blood pressure, and mean arterial pressure in
      the 2K1C animals. In addition, morphine decreased plasma rennin activity in the
      2K1C group. Serum concentrations of nitric oxide were also decreased, and
      morphine prevented the reduction of nitric oxide. The baroreflex sensitivity was
      also improved following morphine administration in the 2K1C group. CONCLUSIONS:
      According to the results presented in this study, chronic administration of low
      dose morphine reduces regulated hypertension in the 2K1C rats, probably via a
      nitric oxide-dependent pathway.

PMID- 24878942
TI  - Lovastatin for reduction of leptin in nondialysis patients with type 2 diabetic
      nephropathy.
AB  - INTRODUCTION: Diabetic Nephropathy (DN) is one of the main complications of
      diabetes mellitus, mostly ending to end-stage renal disease. Leptin and C
      reactive protein (CRP), as inflammatory markers implicated in the progression of
      DN, increase in diabetes mellitus, while transferrin and albumin, as members of
      anti-oxidant defense mechanism, are found to decline. MATERIALS AND METHODS: In a
      controlled clinical trial, 65 patients with type 2 DN were assigned to receive
      lovastatin or placebo, for 3 months, to assess statins' impact on serum levels of
      leptin, CRP, transferrin, albumin, and lipid profile. RESULTS: Serum levels of
      CRP (3.52 +/- 4.16 mg/dL to 2.84 +/- 3.06 mg/dL, P = .02), leptin (10.78 +/- 8.30
      mg/dL to 7.80 +/- 5.41 mg/dL, P = .006), low-density lipoprotein cholesterol
      (116.16 +/- 46.54 mg/dL to 85.46 +/- 29.22 mg/dL, P = .001), and total
      cholesterol (199.00 +/- 43.33 mg/dL to 164.67 +/- 35.19 mg/dL, P = .001) were
      lowered after lovastatin therapy. Mean serum level of high-density lipoprotein
      cholesterol increased (40.00 mg/dL to 42.80 mg/dL, P = .005) after the treatment.
      Lovastatin had no significant effect on albumin and transferrin. Placebo did not
      change any of the parameters after 3 months. CONCLUSIONS: The effect of statins
      on the inflammatory markers involved in the development of DN is a new approach
      to evidence supporting the pleiotropic effect of this drug group.

PMID- 24878943
TI  - Effect of intradialytic exercise on echocardiographic findings in hemodialysis
      patients.
AB  - INTRODUCTION: Cardiovascular disease is the major cause of death in hemodialysis
      patients. Regular aerobic or intradialytic exercise may play a role in reducing
      cardiovascular mortality in these patients. The aim of this study was to evaluate
      the relationship between intradialytic exercise and echocardiographic findings.
      METHODS AND MATERIALS: Forty patients were enrolled in the study from Shahrekord
      Hemodialysis Center. They were randomly assigned into the exercise and control
      groups. In the exercise group, the patients had a 30-minute exercise program per
      dialysis session, 3 times a week, for 3 months. Electrocardiography and
      echocardiography were done at the beginning of the study and 3 months later.
      RESULTS: The mean age and body mass index of the patients were 43.2 +/- 10.5
      years and 21.7 +/- 5.4 kg/m2, respectively. Left ventricular ejection fraction
      increased and systolic pulmonary artery pressure and right ventricular size
      decreased significantly after the study in the exercise group patients.
      CONCLUSIONS: Our results showed the improvement of cardiac systolic and diastolic
      function in patients who had physical exercise during dialysis sessions. Regular
      intradialysis exercise can be suggested for hemodialysis patients without cardiac
      disease.

PMID- 24878944
TI  - Free triiodothyronine in hemodialysis patients: link with malnutrition and
      inflammation.
AB  - INTRODUCTION: Free triiodothyronine (FT3) is a marker of comorbidity in end-stage
      renal disease and in many acute and chronic diseases. There is lack of data about
      the link between FT3 levels and malnutrition and inflammation in hemodialysis
      patients. The objective of the present study was to investigate the link between
      FT3 and malnutrition and inflammation in hemodialysis patients. MATERIALS AND
      METHODS: A total of 84 patients were included in the study (38 men and 46 women;
      mean age, 56.2 +/- 14.8 years; hemodialysis duration, 95.72 +/- 10.35 months).
      Serum FT3, free thyroxin, and thyroid-stimulating hormone concentrations were
      determined. Demographic data and laboratory values were evaluated. Patients'
      comorbidity status was determined using the Charlson Comorbidity Index (CCI), and
      malnutrition-inflammation status was determined by Malnutrition-Inflammation
      Score (MIS). RESULTS: Serum FT3 concentration inversely correlated with age (r = 
      0.328, P = .002), CCI (r = -0.591, P = .001), C-reactive protein (r = -0.299, P =
      .01), and MIS (r = -0.671, P = .001), and positively correlated with serum
      albumin (r = 0.389, P = .001). In multivariate linear regression analysis, FT3
      was independently associated with MIS (beta;, -0.14; 95% confidence interval, 
      0.175 to 0.063, P = .003), adjusted for CCI, C-reactive protein level, serum
      albumin level, and MIS. CONCLUSIONS: The results of this study indicate that FT3
      is negatively correlated with inflammatory markers, namely C-reactive protein,
      and it is independently related with MIS in hemodialysis patients. Therefore, we
      suggest that FT3 can be accepted as an inflammatory marker in hemodialysis
      patients.

PMID- 24878945
TI  - Vascular access profile in maintenance hemodialysis patients.
AB  - INTRODUCTION: The aims of this study was to evaluate maintenance hemodialysis
      population in a tertiary care hospital based dialysis unit for vascular access
      (VA) types, to compare native arteriovenous fistula (AVF) and arteriovenous graft
      (AVG) survival, and to assess risk factors for access failure. MATERIALS AND
      METHODS: A total of 182 patients on maintenance hemodialysis were evaluated and
      followed up in terms of VA type and VA outcomes. RESULTS: Among 103 prevalent
      patients, 15.5% initiated dialysis with AVF. At the time of the study, 67.9% of
      the prevalent patients had an AVF and 29.1% had AVG. Of 79 incident patients, 64%
      were followed up for more than 3 months by nephrologists before initiation of
      dialysis. Among these patients, 13.6% were initiated with AVF. There were 25
      primary failures and 50 secondary failure episodes. Of the 50 secondary failures,
      15 were AVF failures and 31 AVG failures. Vascular access survival was
      significantly superior with AVF as compared with AVG (P = .03). With longer
      dialysis periods, failure rates were higher. Follow-up with nephrologists prior
      to initiation of dialysis had a major influence on VA. CONCLUSIONS: Arteriovenous
      fistula is the best VA for maintenance hemodialysis. However, when the
      vasculature is not ideal for AVF, AVG should be constructed. A small percentage
      of our patients had fistula at initiation of dialysis. This is mainly due to late
      nephrology referrals and also due to reluctance of patients to undergo surgical
      access placement when they are relatively asymptomatic.

PMID- 24878946
TI  - Short-term and long-term survival of kidney allograft: cure model analysis.
AB  - INTRODUCTION: Kidney allograft failure is a major concern in kidney transplant
      recipients. We separately assessed risk factors for long-term and short-term
      survival of death-censored kidney allograft. MATERIALS AND METHODS: This study
      included 397 kidney recipients who underwent surgery in Afzalipour Hospital,
      Kerman, Iran, from 2004 to 2010. The Cox mixture cure model was used to fit
      independent variables for prediction of graft survival in short-term and long
      term. RESULTS: Allograft failure occurred in 43 kidney transplant recipients
      (10.8%). Among the long-term survivors, hypertension (odds ratio, 3.35; 95%
      confidence interval [CI], 1.6 to 6.7), a serum creatinine level greater than 1.6
      at hospital discharge (odds ratio, 15.1; 95% CI, 7.2 to 31.9), and donor age
      (odds ratio, 1.14; 95% CI, 1.09 to 1.18) were significant predictors of allograft
      failure. Overweight, obesity, and male donor were associated with better
      survival. In short-term survivors, a high body mass index (hazard ratio, 3.59;
      95% CI, 1.2 to 10.7) and longer duration of pretransplant dialysis (hazard ratio,
      2.4; 95% CI, 1.07 to 5.7) were associated with graft failure, while the risk of
      allograft failure decreased in recipients who received kidney transplants from
      living donors versus deceased donors (hazard ratio, 0.3; 95% CI: 0.11 to 0.78)
      and with each 1-year increase in donor age (hazard ratio, 0.91; 95% CI, 0.86 to
      0.96). CONCLUSIONS: Many efforts have been made to improve short-term survival of
      kidney allograft. The cure analysis extends the knowledge by showing that control
      of which variables can improve both long-term and short-term survival rates.

PMID- 24878947
TI  - Prevalence and risk factors of recurrent cytomegalovirus infection in kidney
      transplant recipients.
AB  - INTRODUCTION: Recurrence of cytomegalovirus (CMV) infection following solid organ
      transplantation causes mortality and morbidity in allograft recipients. The aim
      of this study was to evaluate prevalence and risk factors of recurrent CMV
      infection in kidney transplant patients. MATERIALS AND METHODS: Four hundred and
      twenty-seven consecutive kidney transplant recipients were included in this
      retrospective cohort study. Both donors and recipients were CMV seropositive.
      Recurrent CMV infection (symptomatic or asymptomatic) was defined as detection of
      CMV infection in a patient who has had previously documented infection and who
      had not have virus detected for an interval of at least 4 weeks during active
      surveillance. RESULTS: Of 427 recipients, 71 (16.6%) had CMV infection, of which
      19 (4.4%) were recurrent infection. Donor source, dialysis duration before
      transplantation, recipient and donor age and sex, and administration of
      antithymocyte globulin and prophylactic treatment ganciclovir were not associated
      with CMV infection or recurrence. The use of tacrolimus in the immunosuppressive
      regimen as compared to cyclosporine was an independent risk factor for CMV
      infection but not recurrent infection. CONCLUSIONS: Intensive immunosuppressive
      regimen, such as using tacrolimus, might be associated with a higher risk for CMV
      infection, but this study was not able to document the same association for
      recurrent CMV disease. In patients receiving immunosuppressive regimens that
      include tacrolimus and antithymocyte globulin, prophylactic treatment for CMV
      disease with ganciclovir is recommended.

PMID- 24878948
TI  - Prevalence of fibromyalgia in hemodialysis patients.
AB  - This study sought to determine the prevalence of fibromyalgia syndrome and to
      identify whether fibromyalgia was associated with various clinical symptoms and
      laboratory parameters in hemodialysis patients. One hundred and forty-eight
      hemodialysis patients were examined for fibromyalgia symptoms according to the
      American College of Rheumatology criteria. Demographic characteristics, as well
      as causes of kidney failure, dialysis duration, and symptoms related to
      fibromyalgia were investigated. Of 148 patients, 18 (12.2%) were diagnosed with
      fibromyalgia. Patients with fibromyalgia had significantly poorer sleeping
      satisfaction than the control group (P = .02).The Beck Depression Inventory score
      was higher in 77.8% of the fibromyalgia patients than that in the control group
      (P = .006), but there was no significant difference in the anxiety score between
      the two groups (P = .86).In conclusion, there was a higher prevalence of
      fibromyalgia in hemodialysis patients than previously reported. Sleep
      disturbances and depression levels correlated with fibromyalgia. 

PMID- 24878949
TI  - Ciprofloxacin-induced crystal nephropathy.
AB  - Ciprofloxacin is a commonly used antibiotic. Renal side effects are rare and are
      usually immune mediated. Clinical and experimental studies have suggested that
      crystalluria and crystal nephropathy occur in alkaline urine. Preexisting kidney
      function impairment, high dose of the medication, and advanced age predispose to
      this complication. We report a case of crystal nephropathy in a young woman
      treated with ciprofloxacin and a nonsteroidal anti-inflammatory drug. 

PMID- 24878950
TI  - Coexistence of autosomal dominant polycystic kidney disease and amyloidosis in a
      patient with nephrotic-range proteinuria.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is an inherited disorder
      characterized by the development and growth of cysts in the kidneys. Non
      nephritic-range proteinuria is a common presentation in ADPKD patients; however,
      nephrotic syndrome is a rare coincidence. A 52-year-old man is described who was
      diagnosed with secondary amyloidosis with ADPKD. To our knowledge, this is the
      first case of amyloidosis associated with frequently infected renal cysts.
      Patients with ADPKD who show massive proteinuria should be investigated in terms
      of concomitant glomerular disease. 

PMID- 24878951
TI  - Acute phosphate nephropathy.
AB  - We present acute phosphate nephropathy in a 28-year-old man, which was developed
      after a car accident due to rhabdomyolysis. Treatment of acute kidney injury was
      done with administration of sodium bicarbonate. 

PMID- 24878952
TI  - Delayed diagnosis of Alport syndrome without hematuria.
AB  - Alport syndrome is a progressive hereditary disease caused by mutations in the
      genes encoding type IV collagen. Persistent microscopic hematuria is the hallmark
      of Alport syndrome, occurring in almost all boys according to previous reports.
      We report the case of a 20-year-old man presented with proteinuria but no
      hematuria that was initially misdiagnosed with refractory nephrotic syndrome and
      was eventually diagnosed with Alport syndrome following kidney and skin biopsy.
      During the follow-up period, he experienced a rapid progression to end-stage
      renal disease. Timely diagnosis of Alport syndrome is important, because patients
      may benefit from early intervention and avoid suffering from unnecessary
      nephrotoxic drug use. 

PMID- 24878953
TI  - Pre-uremic calciphylaxis.
AB  - Calciphylaxis is characterized by calcification and thrombosis of arteries
      resulting in ischemic necrosis of predominantly skin and subcutaneous tissue.
      Primarily affecting patients with end-stage renal disease, calciphylaxis is
      diagnosed rarely in the absence of renal replacement therapy. We report an
      elderly obese woman presented with leg pain and ulceration. She had chronic
      kidney disease, diabetes mellitus, hypertension, and peripheral vascular disease.
      Angiography revealed occlusion of the left superficial femoral, popliteal, and
      distal tibial arteries. Amputation was performed. Histological examination
      demonstrated medial calcification, intimal hyperplasia, and thrombosis of small-
      and medium-sized arteries in the subcutaneous tissue. This case features
      calciphylaxis in a patient with chronic kidney disease before the onset of
      uremia. Calciphylaxis and atherosclerotic peripheral vascular disease have
      several risk factors in common. This report calls attention to a disorder that
      can be masqueraded as leg ulceration due to peripheral vascular disease in the
      absence of renal replacement therapy. 

PMID- 24878954
TI  - Re: Relationship between serum intact parathyroid hormone and pruritus in
      hemodialysis patients.

PMID- 24878955
TI  - Re: NPHS2 gene in steroid-resistant nephrotic syndrome: prevalence, clinical
      course, and mutational spectrum in south-west Iranian children.

PMID- 24878957
TI  - The U3 region of Moloney murine leukemia virus contains position-independent cis
      acting sequences involved in the nuclear export of full-length viral transcripts.
AB  - The distinguishing feature of self-inactivating (SIN) retroviral vectors is the
      deletion of the enhancer/promoter sequences in the U3 region of the 3' long
      terminal repeat. This design is used to overcome transcriptional interference and
      prevent downstream transcription from the 3' long terminal repeat. SIN vectors
      were derived from a number of different retroviruses. Studies of SIN vectors show
      that extensive U3 deletions in HIV-based vectors do not alter viral titers or the
      in vitro and in vivo properties of the vectors. However, deletion of the U3
      sequences in gamma- and alpha-retroviruses correlates with defects in 3' RNA
      processing and reduces viral titers by >10-fold. Here, we studied the steps in
      the retroviral life cycle that are affected by the deletion of sequences in the
      3' U3 region of Moloney murine leukemia virus-derived retroviral vectors. The
      results show that the amounts of both full-length and internal RNA transcripts of
      U3-minus vectors are reduced in the nuclei of transfected cells, an effect that
      is probably due to a general defect in 3' RNA processing. Furthermore, full
      length RNA transcripts were also defective in terms of nuclear export. This
      defect was complemented by transferring the U3 region to another position within
      the retroviral vector, indicating that the U3 region contains position
      independent cis-acting sequences that are required for the transport of full
      length viral transcripts. The results also suggest that the leader region of
      Moloney murine leukemia virus contains inhibitory/regulatory sequences, which
      prevent export and mediate nuclear retention of full-length viral RNA. 

PMID- 24878958
TI  - Role of 6-O-sulfated heparan sulfate in chronic renal fibrosis.
AB  - Heparan sulfate (HS) plays a crucial role in the fibrosis associated with chronic
      allograft dysfunction by binding and presenting cytokines and growth factors to
      their receptors. These interactions critically depend on the distribution of 6-O
      sulfated glucosamine residues, which is generated by glucosaminyl-6-O
      sulfotransferases (HS6STs) and selectively removed by cell surface HS-6-O
      endosulfatases (SULFs). Using human renal allografts we found increased
      expression of 6-O-sulfated HS domains in tubular epithelial cells during chronic
      rejection as compared with the controls. Stimulation of renal epithelial cells
      with TGF-beta induced SULF2 expression. To examine the role of 6-O-sulfated HS in
      the development of fibrosis, we generated stable HS6ST1 and SULF2 overexpressing
      renal epithelial cells. Compared with mock transfectants, the HS6ST1
      transfectants showed significantly increased binding of FGF2 (p = 0.0086) and
      pERK activation. HS6ST1 transfectants displayed a relative increase in mono-6-O
      sulfated disaccharides accompanied by a decrease in iduronic acid 2-O-sulfated
      disaccharide structures. In contrast, SULF2 transfectants showed significantly
      reduced FGF2 binding and phosphorylation of ERK. Structural analysis of HS showed
      about 40% down-regulation in 6-O-sulfation with a parallel increase in iduronic
      acid mono-2-O-sulfated disaccharides. To assess the relevance of these data in
      vivo we established a murine model of fibrosis (unilateral ureteric obstruction
      (UUO)). HS-specific phage display antibodies (HS3A8 and RB4EA12) showed
      significant increase in 6-O-sulfation in fibrotic kidney compared with the
      control. These results suggest an important role of 6-O-sulfation in the
      pathogenesis of fibrosis associated with chronic rejection. 

PMID- 24878959
TI  - Nuclear translocation uncovers the amyloid peptide Abeta42 as a regulator of gene
      transcription.
AB  - Although soluble species of the amyloid-beta peptide Abeta42 correlate with
      disease symptoms in Alzheimer disease, little is known about the biological
      activities of amyloid-beta (Abeta). Here, we show that Abeta peptides varying in
      lengths from 38 to 43 amino acids are internalized by cultured neuroblastoma
      cells and can be found in the nucleus. By three independent methods, we
      demonstrate direct detection of nuclear Abeta42 as follows: (i) biochemical
      analysis of nuclear fractions; (ii) detection of biotin-labeled Abeta in living
      cells by confocal laser scanning microscopy; and (iii) transmission electron
      microscopy of Abeta in cultured cells, as well as brain tissue of wild-type and
      transgenic APPPS1 mice (overexpression of amyloid precursor protein and
      presenilin 1 with Swedish and L166P mutations, respectively). Also, this study
      details a novel role for Abeta42 in nuclear signaling, distinct from the amyloid
      precursor protein intracellular domain. Chromatin immunoprecipitation showed that
      Abeta42 specifically interacts as a repressor of gene transcription with LRP1 and
      KAI1 promoters. By quantitative RT-PCR, we confirmed that mRNA levels of the
      examined candidate genes were exclusively decreased by the potentially neurotoxic
      Abeta42 wild-type peptide. Shorter peptides (Abeta38 or Abeta40) and other longer
      peptides (nontoxic Abeta42 G33A substitution or Abeta43) did not affect mRNA
      levels. Overall, our data indicate that the nuclear translocation of Abeta42
      impacts gene regulation, and deleterious effects of Abeta42 in Alzheimer disease
      pathogenesis may be influenced by altering the expression profiles of disease
      modifying genes. 

PMID- 24878960
TI  - MicroRNA miR-124 controls the choice between neuronal and astrocyte
      differentiation by fine-tuning Ezh2 expression.
AB  - Polycomb group protein Ezh2 is a histone H3 Lys-27 histone methyltransferase
      orchestrating an extensive epigenetic regulatory program. Several nervous system
      specific genes are known to be repressed by Ezh2 in stem cells and derepressed
      during neuronal differentiation. However, the molecular mechanisms underlying
      this regulation remain poorly understood. Here we show that Ezh2 levels are
      dampened during neuronal differentiation by brain-enriched microRNA miR-124.
      Expression of miR-124 in a neuroblastoma cells line was sufficient to up-regulate
      a significant fraction of nervous system-specific Ezh2 target genes. On the other
      hand, naturally elevated expression of miR-124 in embryonic carcinoma cells
      undergoing neuronal differentiation correlated with down-regulation of Ezh2
      levels. Importantly, overexpression of Ezh2 mRNA with a 3'-untranslated region
      (3'-UTR) lacking a functional miR-124 binding site, but not with the wild-type
      Ezh2 3'-UTR, hampered neuronal and promoted astrocyte-specific differentiation in
      P19 and embryonic mouse neural stem cells. Overall, our results uncover a
      molecular mechanism that allows miR-124 to balance the choice between alternative
      differentiation possibilities through fine-tuning the expression of a critical
      epigenetic regulator.

PMID- 24878963
TI  - Pain and discomfort in the anophthalmic socket.
AB  - PURPOSE OF REVIEW: The aim of this review is to summarize causes of pain and
      discomfort in the anophthalmic socket and to aid the clinician in evaluating
      anophthalmic patients. RECENT FINDINGS: Causes of pain and discomfort can be
      categorized into dysfunctional orbit/anophthalmic socket, phantom eye pain, and
      psychological/psychiatric factors. Recent research has brought attention to the
      role of prosthesis deposits in mucous formation, meibomian gland dysfunction
      causing dry socket, and the anophthalmic patients' experience of phantom eye
      pain. SUMMARY: Anophthalmic patients may experience pain and discomfort for a
      variety of reasons. The treating physician needs to recognize this as treatment
      options are distinctly different.

PMID- 24878964
TI  - Modelling of loading, stress relaxation and stress recovery in a shape memory
      polymer.
AB  - A multi-element constitutive model for a lactide-based shape memory polymer has
      been developed that represents loading to large tensile deformations, stress
      relaxation and stress recovery at 60, 65 and 70 degrees C. The model consists of
      parallel Maxwell arms each comprising neo-Hookean and Eyring elements. Guiu-Pratt
      analysis of the stress relaxation curves yields Eyring parameters. When these
      parameters are used to define the Eyring process in a single Maxwell arm, the
      resulting model yields at too low a stress, but gives good predictions for longer
      times. Stress dip tests show a very stiff response on unloading by a small strain
      decrement. This would create an unrealistically high stress on loading to large
      strain if it were modelled by an elastic element. Instead it is modelled by an
      Eyring process operating via a flow rule that introduces strain hardening after
      yield. When this process is incorporated into a second parallel Maxwell arm,
      there results a model that fully represents both stress relaxation and stress dip
      tests at 60 degrees C. At higher temperatures a third arm is required for valid
      predictions. 

PMID- 24878961
TI  - A cell-penetrating antibody fragment against HIV-1 Rev has high antiviral
      activity: characterization of the paratope.
AB  - The HIV-1 protein Rev oligomerizes on viral transcripts and directs their nuclear
      export. Previously, a Fab against Rev generated by phage display was used to
      crystallize and solve the structure of the Rev oligomerization domain. Here we
      have investigated the capability of this Fab to block Rev oligomerization and
      inhibit HIV-1 replication. The Fab itself did not have antiviral activity, but
      when a Tat-derived cell-penetrating peptide was appended, the resulting molecule
      (FabRev1-Tat) was strongly inhibitory of three different CCR5-tropic HIV-1
      isolates (IC50 = 0.09-0.44 MUg/ml), as assessed by suppression of reverse
      transcriptase activity in infected peripheral blood mononuclear cells, and had
      low cell toxicity (TC50 > 100 MUg/ml). FabRev1-Tat was taken up by both
      peripheral blood mononuclear and HEK293T cells, appearing in both the cytoplasm
      and nucleus, as shown by immunofluorescence confocal laser scanning microscopy.
      Computational alanine scanning was used to identify key residues in the
      complementarity-determining regions to guide mutagenesis experiments. Residues in
      the light chain CDR3 (LCDR3) were assessed to be important. Residues in LCDR3
      were mutated, and LCDR3-Tyr(92) was found to be critical for binding to Rev, as
      judged by surface plasmon resonance and electron microscopy. Peptides
      corresponding to all six CDR regions were synthesized and tested for Rev binding.
      None of the linear peptides had significant affinity for Rev, but four of the
      amide-cyclic forms did. Especially cyclic-LCDR3 (LGGYPAASYRTA) had high affinity
      for Rev and was able to effectively depolymerize Rev filaments, as shown by both
      surface plasmon resonance and electron microscopy. 

PMID- 24878962
TI  - A mechanism for the auto-inhibition of hyperpolarization-activated cyclic
      nucleotide-gated (HCN) channel opening and its relief by cAMP.
AB  - Hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channels control
      neuronal and cardiac electrical rhythmicity. There are four homologous isoforms
      (HCN1-4) sharing a common multidomain architecture that includes an N-terminal
      transmembrane tetrameric ion channel followed by a cytoplasmic "C-linker," which
      connects a more distal cAMP-binding domain (CBD) to the inner pore. Channel
      opening is primarily stimulated by transmembrane elements that sense membrane
      hyperpolarization, although cAMP reduces the voltage required for HCN activation
      by promoting tetramerization of the intracellular C-linker, which in turn
      relieves auto-inhibition of the inner pore gate. Although binding of cAMP has
      been proposed to relieve auto-inhibition by affecting the structure of the C
      linker and CBD, the nature and extent of these cAMP-dependent changes remain
      limitedly explored. Here, we used NMR to probe the changes caused by the binding
      of cAMP and of cCMP, a partial agonist, to the apo-CBD of HCN4. Our data indicate
      that the CBD exists in a dynamic two-state equilibrium, whose position as gauged
      by NMR chemical shifts correlates with the V1/2 voltage measured through
      electrophysiology. In the absence of cAMP, the most populated CBD state leads to
      steric clashes with the activated or "tetrameric" C-linker, which becomes
      energetically unfavored. The steric clashes of the apo tetramer are eliminated
      either by cAMP binding, which selects for a CBD state devoid of steric clashes
      with the tetrameric C-linker and facilitates channel opening, or by a transition
      of apo-HCN to monomers or dimer of dimers, in which the C-linker becomes less
      structured, and channel opening is not facilitated. 

PMID- 24878965
TI  - Multi-phonon scattering processes in one-dimensional anharmonic biological
      superlattices: understanding the dissipation of mechanical waves in mineralized
      tissues.
AB  - The scattering of elastic waves in a one dimensional phononic (PnC) crystal
      composed of alternate collagen and hydroxy-apatite constituent layers is studied.
      These superlattices are metaphors for mineralized tissues present in bones and
      teeth. The collagen is treated as an open system elastic medium with water
      content which can vary depending on the level of stress applied. The open system
      nature of the collagen-water system leads to a non-linear stress-strain response.
      The finite difference time domain method is employed to investigate the
      propagation of non-linear mechanical waves through the superlattice. The spectral
      energy density method enables the calculation of the non-linear vibrational wave
      band structure. The non-linearity in the mechanical response of the collagen
      water system enables a variety of multi-phonon scattering processes resulting in
      an increase in the number of channels for the dissipation of elastic waves and
      therefore for the dissipation of mechanical energy. These results provide an
      explanation for the relationship between bone fragility and decreased hydration. 

PMID- 24878966
TI  - A review of the current published spinal literature regarding bone morphogenetic
      protein-2: an insight into potential bias.
AB  - Recombinant human bone morphogenetic protein-2 (rhBMP-2) is a potent biologic
      agent that carries both osteoinductive and osteoconductive properties. Its
      potential as an autologous bone graft substitute in spine surgery led to its
      approval by the United States Food and Drug Administration (FDA) in 2002
      following a series of industry-sponsored trials. Although approved for a single
      level anterior lumbar interbody fusion from L4-S1 with a proprietary cage, the
      off-label use of rhBMP-2 rapidly escalated. Soon thereafter, reports of serious
      and potentially life-threatening complications associated with rhBMP-2 began
      emerging, which sparked concerns with regards to potential bias in the original
      FDA trials. Ultimately, an independent review of all published and unpublished
      data on the safety and effectiveness of rhBMP-2 by the Yale University Open Data
      Access (YODA) Project determined that while rhBMP-2 is as effective as iliac
      crest bone graft (ICBG) in potentiating spinal fusion, there was significant bias
      and conflicts of interests that resulted in an underreporting of complications in
      the original industry-sponsored trials. 

PMID- 24878967
TI  - Lessons from the infuse trials: do we need a classification of bias in scientific
      publications and editorials?
AB  - The original 13 Food and Drug Administration industry-sponsored recombinant human
      bone morphogenetic protein-2 (rhBMP-2) trials investigating its use in spinal
      fusion all reported no associated adverse events. However, subsequent series of
      studies began reporting complication rates that were much higher than those that
      were initially published. Critical analysis of the original rhBMP-2 industry
      associated data found systematic alignment favoring positive outcomes with no
      proven clinical advantage over bone graft. The sources of potential bias leading
      to inaccurate reporting of original rhBMP-2 efficacy and safety profile include
      flawed study design, methodological technique, data reporting and analysis, and
      significant financial conflict of interest. As such, to ensure the integrity of
      the scientific literature, further measures should be taken by researchers,
      surgeons, authors, journal editors and reviewers to assess for potential sources
      of bias. 

PMID- 24878969
TI  - Measuring masses of large biomolecules and bioparticles using mass spectrometric
      techniques.
AB  - Large biomolecules and bioparticles play a vital role in biology, chemistry,
      biomedical science and physics. Mass is a critical parameter for the
      characterization of large biomolecules and bioparticles. To achieve mass
      analysis, choosing a suitable ion source is the first step and the instruments
      for detecting ions, mass analyzers and detectors should also be considered.
      Abundant mass spectrometric techniques have been proposed to determine the masses
      of large biomolecules and bioparticles and these techniques can be divided into
      two categories. The first category measures the mass (or size) of intact
      particles, including single particle quadrupole ion trap mass spectrometry, cell
      mass spectrometry, charge detection mass spectrometry and differential mobility
      mass analysis; the second category aims to measure the mass and tandem mass of
      biomolecular ions, including quadrupole ion trap mass spectrometry, time-of
      flight mass spectrometry, quadrupole orthogonal time-of-flight mass spectrometry
      and orbitrap mass spectrometry. Moreover, algorithms for the mass and
      stoichiometry assignment of electrospray mass spectra are developed to obtain
      accurate structure information and subunit combinations. 

PMID- 24878968
TI  - Genetic polymorphisms of interleukin-1 beta and osteosarcoma risk.
AB  - PURPOSE: Osteosarcoma is the most common childhood bone cancer. Interleukin-1
      beta (IL-1B) is crucially involved in osteosarcoma carcinogenesis. Whether
      genetic polymorphisms of IL-1B also influence osteosarcoma risk is unknown. The
      aim of this study was to investigate the association between IL-1B gene
      polymorphisms and osteosarcoma risk in Chinese Han patients. METHODS: A hospital
      based case-control study involving 120 osteosarcoma patients and 120 controls was
      conducted. Polymerase chain reaction restriction fragment length polymorphism
      (PCR-RFLP) analysis was performed to detect three IL-1B gene polymorphisms (-31
      T/C, -511 C/T and +3954 C/T) in these patients. RESULTS: Patients with
      osteosarcoma had a significantly lower frequency of -31 CC genotype [odds ratio
      (OR) = 0.40, 95% confidence interval (CI) = 0.17-0.92; P = 0.03] and -31 C allele
      (OR = 0.67, 95% CI = 0.46-0.99; P = 0.04) than controls. Patients with
      osteosarcoma had a significantly lower frequency of -511 TT genotype (OR = 0.40,
      95% CI = 0.17-0.95; P = 0.04) than controls. The +3954 C/T gene polymorphisms
      were not associated with a risk of osteosarcoma. When stratified by Enneking
      stage, tumour location, histological type, tumour metastasis of osteosarcoma and
      family history of cancer, no statistically significant results were found.
      CONCLUSIONS: This is the first study to provide evidence for an association of IL
      1B gene polymorphisms with osteosarcoma risk.

PMID- 24878970
TI  - A rare case of limbic encephalitis with anti leucine-rich glioma inactivated-1
      (LGI1) antibodies.
AB  - We report a case of limbic encephalitis with LGI1 antibodies and cranial MRI
      abnormality. A 41-year-old woman who presented with confusional state that had
      started 1 month ago. Brain magnetic resonance imaging revealed hyperintense
      signal in right basal ganglia followed by hyperintense signals in left
      hippocampus and bilateral basal ganglia half a month later. This case expands the
      spectrum of limbic encephalitis to include LGI1 antibodies and cranial MRI
      changing process. 

PMID- 24878971
TI  - Antidepressant-like effects and mechanism of action of SYG in depression model in
      rats.
AB  - OBJECTIVES: The present study aimed to evaluate whether SYG, a Chinese herbal
      formula, could produce antidepressant-like effects in learned helplessness (LH)
      model and chronic mild stress (CMS) model in rats. The mechanism underlying the
      antidepressant-like action was investigated by exploring BDNF signaling way in
      the hippocampus. MATERIAL AND METHODS: SYG was administrated for 5 consecutive
      days (100 and 200 mg/kg/day, intragastrically) in the learned helplessness model;
      SYG was administered daily by gastric gavages during both the 5-week stress
      session and behavior tests periods in the chronic mild stress model (100 and 200
      mg/kg). The serum corticosterone level was measured in the learned helplessness
      model. Levels of BDNF and Tyrosine-related kinase B (TrkB), were evaluated in the
      hippocampus of chronic mild stress model. RESULTS: A deficit in avoidance
      learning and higher corticosterone level were observed in learned helplessness
      rats. SYG significantly reduced this deficit and reversed the corticosterone
      alteration. CMS induced significant reduction of sucrose intake in the sucrose
      preference test, an increased latency to feed in the novelty-suppressed feeding
      test and an increased immobility time in the forced swim test as compared to the
      control. It was also found that BDNF and TrkB levels were decreased in CMS model.
      Chronic treatment of SYG significantly suppressed the behavioral changes and up
      regulated the BDNF signal pathway in the hippocampus. CONCLUSION: Our results
      suggest that SYG alleviates depression induced by LH and CMS model. The
      antidepressant-like activity of SYG is likely mediated by activation the BDNF
      signal pathway in the hippocampus.

PMID- 24878973
TI  - Cytokines, diabetes mellitus and psychopathology: a challenging combination.
AB  - OBJECTIVES: The aim of this study was to investigate the association of IL-6, IL
      12, and TNF-alpha with trait and state psychological factors in type 2 diabetic
      patients. DESIGN: Patients were divided in two groups. Group A consisted of 86
      controlled diabetic patients (HbA1c<7) and the Group B consisted of 45
      uncontrolled diabetic patients (HbA1c >= 7). SETTINGS: During the initial phase
      of the study (T0), blood samples were taken for measuring IL-6, IL-12 and TNF
      alpha serum levels as well as a battery of psychometric instruments. One year
      later (T1), the uncontrolled diabetic patients were re-evaluated with the use of
      the same psychometric instruments and with the identical blood analysis. RESULTS:
      The average values of tnf-alpha were significantly different among controlled
      (7.73 +/- 5.51) and uncontrolled patients (9.29 +/- 4.52) at a significance level
      of 5% (p=0.009). Controlled diabetic patients show a statistically significant
      relationship between IL-6 and neuroticism (rp=0.303, p=0.010), and between IL-12
      and psychotism, (rsp=0.382, p=0.001). Controlled diabetic patients show a
      statistically significant relationship between IL-12 and the act out hostility
      (rsp=-0.307, p=0.009). The scores of the psychometric tests differ significantly
      between the first and second evaluation. Acting out hostility and the direction
      of hostility increased when HbA1c values fell below the threshold of 7, while the
      total hostility index, as well as all other scales, dropped when patients
      controlled their metabolic profile. CONCLUSIONS: The present results provide
      evidence that IL-6, IL-12 and TNF-alpha are closely related to the course and
      treatment of type 2 diabetes.

PMID- 24878972
TI  - Cervical neuroendocrine tumor in a young female with Lynch Syndrome.
AB  - Neuroendocrine tumors rarely occur in the cervix or other components of the
      reproductive system. These tumors have been associated with microsatellite
      instability, are very aggressive and often associated with poor outcome. Lynch
      syndrome is an inherited cancer syndrome that has also been associated with
      microsatellite instability. Here we report a 34-year-old female with Lynch
      syndrome and a family history of loss of DNA mismatch of the hereditary non
      polyposis colorectal cancer repair gene expression who presented with a
      neuroendocrine tumor of her cervix as the first manifestation of Lynch syndrome.
      This is the first case reported of a neuroendocrine tumor of the cervix in a
      patient with Lynch syndrome. We also review the relationship between Lynch
      Syndrome and neuroendocrine tumors. 

PMID- 24878974
TI  - Detection of protein homolougs with HIV-1 antigens in bacteria of positive
      patients - phase II.
AB  - OBJECTIVES: Human immunodeficiency virus type 1 is widely accepted as the cause
      of AIDS (Acquires Immunodeficiency Syndrome) but it is necessary to consider
      other factors, not only HIV, which may be involved in AIDS process. It is
      apparent that a viral reservoir persists in virtually all infected individuals
      receiving HAART. Reservoirs were detected in macrophages and other cells of the
      blood system, in which even very effective HAART was not able to eliminate the
      virus. Over the last period of time AIDS research has been focused on the gut and
      other mucosal tissue as the major site of HIV infection and CD4+ T cells loss.
      Intestinal bacteria and cells associated with GIT are in close vicinity and so
      has been raised the idea that bacteria may be involved in AIDS pathogenesis.
      Matherial/Methods: Bacteria and yeast isolated from a cohort of 67 Cambodian and
      Kenyan HIV positive children and from a cohort of 62 Slovak and American AIDS
      patients were analyzed for detection of expression of HIV-1 antigens p17, p24,
      p55, gp41 and gp120 (Abcam, UK). RESULTS: By monoclonal antibodies against HIV-1
      proteins p17 and p55 was detected protein with molecular weight of 45-55 kDa. In
      samples of Cambodian and Kenyan HIV positive children was found 35 kDa protein
      using MAb against HIV-specific protein p17. By using MAbs against p24 was found
      protein of 55-60 kDa in Cambodian and Kenyan samples but, suprisingly, no
      proteins were detected in bacterial extracts of American and Slovak AIDS patients
      by this MAbs. Using monoclonal antibodies against HIV-1 specific protein gp41 was
      positive signal identified in 30-35% of samples from both cohorts of patients
      from Kenya and Cambodia and in 75% of samples from American and Slovak patients.
      The protein of about 75-85 kDa was detected by MAbs against gp120 only in protein
      extracts obtained from yeasts Candida sp. of Cambodian and Kenyan HIV positive
      children. CONCLUSION: The molecular weight of 55 kDa protein was detected by MAbs
      anti HIV p24, p17+p55. Its molecular weight is comparable to gag-encoded Pr55Gag
      precursor. Surprisingly, such proteins were not found in bacterial extract from
      samples of American and Slovak patients by using the MAbs against HIV-specific
      protein p24. The protein of about 75-85 kDa was detected only in Candida species
      protein extracts of Cambodian and Kenyan HIV positive children by the MAbs
      against gp120. In Slovak and American samples, protein reacting with MAbs anti
      gp120 was not found. These results suggest that there are specific differences
      between Slovak and American HIV positive patients bacterial proteins on one side
      and Cambodian and Kenyan on the other. These differences may suggest a diverse
      bacterial evolution in various geographical areas.

PMID- 24878975
TI  - Glycogen storage disease-like phenotype with central nervous system involvement
      in a PGM1-CDG patient.
AB  - OBJECTIVES: A 10-year-old boy presented with cleft palate, hepatopathy,
      cholecystolithiasis, myopathy, coagulopathy, hyperlipidemia, hypoglycemia,
      hyperuricemia, short stature, obesity, hypothyroidism, microcephaly and mild
      intellectual disability. The multi-systemic manifestation involving certain
      distinct clinical features prompted us to search for a subtype of congenital
      disorders of glycosylation (CDG). METHODS: The patient was screened for CDG by
      examining the distribution of transferrin (TRF) and apolipoprotein C-III (ApoC
      III) sialylated isoforms using isoelectric focusing of serum. This was followed
      by spectrophotometric measurement of phosphoglucomutase 1 (PGM1) activity in
      fibroblasts and molecular analysis including sequencing and PCR-RFLP of PGM1
      gene. Selected bioinformatics tools were used to evaluate the data. RESULTS:
      Increased relative levels of di-, mono- and asialotransferrin reflected a defect
      of N-glycosylation in the patient. Markedly decreased activity of PGM1
      corresponding to less than 5% of control's was found. Sequencing of PGM1 gene
      revealed the presence of two heterozygous missense mutations c.1010C>T (p.T337M)
      and c.1508G>A (p.R503Q), whose pathogenicity was confirmed by in silico analysis.
      CONCLUSION: We report the first Czech patient with a glycosylation disorder due
      to PGM1 deficiency. Compared to the described cases, no dilated cardiomyopathy
      was noted in our patient. However, he suffered from a mild neurological
      impairment, which is an uncommon feature that extends the phenotype associated
      with PGM1-CDG. Lactose-rich diet, which was previously reported to have
      ameliorated the clinical symptoms in some PGM1-CDG patients, did not result in
      any improvement in our patient.

PMID- 24878976
TI  - Incidence of skeletal muscle disorders after statins' treatment: consequences in
      clinical and EMG picture.
AB  - OBJECTIVES: The goal of this clinical trial was to determine the incidence of
      undesirable side effects, and to ascertain any occurrence of genetic
      polymorphisms. MATERIAL AND METHODS: Clinically, we looked for manifestations of
      a benign myositis and of serious rhabdomyolysis. We observed a group 198 patients
      treated with statins, primarially fluvastatin and rosuvastatin. There were 126
      (mean age = 58.3 +/- 4.1; male 91, mean age = 57.4 +/- 5.9; female 35, mean age =
      60.5 +/- 6.5) patients in a subgroup where we administered rosuvastatin.
      Undesirable muscular signs and symptoms were present in 32 patients (25.39%). In
      11 (8.73% of the total 126) CK level increased maximally to 4 times ULN, in 6
      (4.7%) statins were excluded because of very intense subjective suffering. CK
      levels 2-5 times ULN were present in 9 (7.14%). CK blood levels over 10 times ULN
      or higher indicated statins exclusion in 2 (1.58%). Increased levels of the
      further muscular enzyme AST by 5 times ULN were present in 16 (12.69%), up to 10
      times ULN in 2 (1.58%), and over 10 times ULN also in 2 (1.58%). RESULTS: We
      observed rhabdomyolysis in 6 patients (3.03% of the total 198 patients group)
      using other types of statins (three of them undergo chronic hemodialysis). In
      this group we performed molecular-genetic analysis of the following proteins
      relating to statin myopathy: SLCO1B1(388AA/AG-521TT) - (discovered polymorphism
      in 1 patient), further cytochroms Cyp 2C9 (in 1 patient), 2C8 (in 1 patient), Cyp
      SA/4 (non discovered positivity) and finally UGT1A1*2B (discovered in 2
      patients). CONCLUSIONS: In the group of patients treated by rosuvastatin, we
      discovered not one case of rhabdomyolysis. In each patient with rhabdomyolysis
      (brown urine discoloration, mal-odorous urine, painful muscle cramps, muscle
      weakness, fatigue) at least one polymorphism of "statins' genes" was present.

PMID- 24878977
TI  - Low T3 syndrome predicts severe neurological deficits of cerebral infarction
      inpatients with large artery artherosclerosis in internal carotid artery system.
AB  - OBJECTIVES: The low triiodothyronine (T3) syndrome indicates poor prognosis for
      patients with cerebral infarction. It is unknown, however, whether basic
      conditions or severities in the patients with the low T3 syndrome are different
      compared to those without the low T3 syndrome. METHODS: We compared the risk
      factors and the severity of the disease using the National Institutes of Health
      stroke scale (NIHSS) score at the worst condition for cerebral infarction in
      patients with or without the low T3 syndrome in order to better understand the
      characteristics underlying the worse prognosis in patients with the low T3
      syndrome. RESULTS: We found that cerebral infarction patients with the low T3
      syndrome were significantly older (p<0.001) and significantly more likely to be
      female (p=0.002) and had hypertension (p=0.04) or homocystinemia (p=0.001), but
      less likely to smoke (p=0.008), compared to patients without the low T3 syndrome.
      The proportion of NIHSS score >=8 in the patients with LAA-ICA-associated
      cerebral infarction accompanied by the low T3 syndrome was significantly higher
      than in those without the low T3 syndrome (p=0.001). CONCLUSION: We concluded
      that increased numbers of risk factors for cerebral infarction and more severe
      neurological deficits may be important causes for worse prognosis in the patients
      with the low T3 syndrome which may more likely occur in patients with LAA-ICA
      cerebral infarction. Intense secondary prevention in cerebral infarction
      especially in older women are needed.

PMID- 24878979
TI  - Systematic hypothesis for post-stroke depression caused inflammation and
      neurotransmission and resultant on possible treatments.
AB  - Post-stroke depression (PSD) is a prevalent complex psychiatric disorder that
      causes delay to functional recovery from rehabilitation and also increases
      cognitive impairment. The etiology of PSD remains controversial and appears to be
      physical and psycho-social in origin, alone or in combination. The causes of PSD
      as well as the mechanisms conferring beneficial antidepressant effects in the
      context of ischemic brain injury are still unknown. In addition, appropriate
      treatment strategies for therapy to prevent stroke-induced depression-like
      behavior remain to be developed. This paper, therefore, proposes two hypotheses
      for post-stroke depression: The inflammatory hypothesis, which is the increased
      production of proinflammatory cytokines resulting from brain ischemia in cerebral
      areas causing the pathogenesis of post-stroke depression and the glutamate
      hypothesis, where the excess glucocorticoids released from stress-induced over
      activation of hypothalamus-pituitary-adrenal (HPA) lead to dysfunction of
      glutamatergic transmission. Neurotrophins, especially brain-derived neurotrophic
      factor (BDNF) and vascular endothelial growth factor (VEGF) both play various
      roles in the central nervous system (CNS), attenuate apoptosis in cultured
      neurons, stimulate neurogenesis and increase survival and protect neuronal
      tissues from cell death induced by ischemia or depression. We also touch upon
      recent treatment strategies including inhibition of pro-inflammatory cytokines,
      SSRI, neurotrophins and cell-based therapies. In the present review, we provide
      an overview of recent evidence concerning the mechanisms of post-stroke
      depression and propose four prospective treatment strategies so as to provide
      references for clinical evidence-based medications. 

PMID- 24878978
TI  - Predictors of impaired endothelial function in obstructive sleep apnea syndrome.
AB  - OBJECTIVES: Obstructive sleep apnea syndrome (OSA) is associated with increased
      cardiovascular morbidity and mortality. Endothelial dysfunction (ED), accelerated
      atherosclerosis and autonomic dysfunction might be the key players responsible
      for development of vascular diseases in patients with OSA. In a population with
      suspected OSA and low burden of cardiovascular risk factors, we therefore aimed
      to investigate the association between potential cardiovascular risk factors
      including OSA-specific indices, ED and autonomic activity. METHODS: ED was
      investigated using reperfusion hyperaemia index (RHI). OSA was assessed using
      standard polysomnography, autonomic activity was assessed using baroreflex
      sensitivity (BRS). RESULTS: We enrolled 31 patients (42.1+/-11.7 years) with OSA.
      Significant inverse correlation was found between RHI and apnea-hypopnea index
      (AHI) (r=-0.550, p=0.001) and between RHI desaturation index (r=-0.533, p=0.002).
      Positive correlation was found between RHI and minimal nocturnal oxygen
      saturation (r=0.394, p=0.028). In a multiple regression model AHI was the only
      significant variable to predict RHI (beta=-0.522, p=0.003). We found no
      correlation between RHI and BRS. RHI in the population with severe OSA (AHI above
      30) was significantly lower than RHI in the rest of the population (p=0.012).
      CONCLUSION: AHI was the only significant independent predictor of impaired
      endothelial function as expressed by RHI. RHI showed no association with BRS in
      patients with OSA.

PMID- 24878980
TI  - The predictor analysis of response to routine treatment in patients with lower
      urinary tract symptoms suggestive of benign prostatic hyperplasia.
AB  - OBJECTIVE: This study tried to test predictors of response to routine treatment
      in patients with lower urinary tract symptoms suggestive of benign prostatic
      hyperplasia (LUTS/BPH). METHODS: Subjects were evaluated at baseline and at week
      12 following routine treatment for LUTS/BPH using the Korean version of the
      International Prostate Symptom Score (IPSS) to measure the severity of LUTS/BPH.
      Demographics and various clinical variables were analyzed by regression analysis.
      RESULTS: Ninety three patients received routine treatment for LUTS/BPH for 12
      weeks in a naturalistic treatment setting. None of demographics and clinical
      variables was different between responders and non-responders. According to
      multivariate regression analysis, the presence of anxiety (OR=0.203), lower
      improvement in the GAD-7 total score (OR=0.755) and lower improvement in the PHQ
      15 total score (OR=0.811) were independent predictors of treatment response after
      12 weeks routine treatment. CONCLUSIONS: We found the positive association of
      improvement in anxiety and somatization with treatment response, while presence
      of anxiety was negatively associated with treatment response, in patients with
      LUTS/BPH. However, additional studies with adequate power and improved designs
      are necessary to support the present findings.

PMID- 24878981
TI  - The significance of plasma adrenomedullin and calcitonin gene-related peptide
      concentration in patients with Type 2 diabetes mellitus who are treated for
      cardiovascular risk factors.
AB  - OBJECTIVES: To evaluate the significance of plasma adrenomedullin and calcitonin
      gene-related peptide (CGRP) concentration in patients with Type 2 diabetes
      mellitus who are treated for hypertension and dyslipidemia. METHOD: Plasma
      adrenomedullin and CGRP concentration, transthoracal echocardiography and ABPM
      were evaluated in 82 patients with Type 2 diabetes mellitus and 41 control
      subjects with no previous cardiovascular disease. All the subjects had casual
      blood pressure <=140/90 mmHg or received antihypertensive medication, were
      treated by statin if LDL cholesterol was>=3mmol/L, by fibrates if
      triacylglyceroles>=2 mmol/L. RESULTS: The mean age was 61+/-6 in patients with
      diabetes mellitus and 61+/-5 years in control subjects (p=0.9). Plasma CGRP was
      3.0+/-1.8 in patients with diabetes mellitus and 2.3+/-1.0 ng/ml in control
      subjects (p=0.09). Plasma adrenomedullin was 2.2+/-0.9 in patients with diabetes
      mellitus and 2.8+/-1.1 ng/ml in control subjects (p=0.01). In patients with
      diabetes mellitus mass index of the left ventricle was significantly higher and
      the parameters of diastolic function were more deteriorated. Plasma
      adrenomedullin and CGRP correlated significantly negatively with serum creatinine
      and positively with mean 24 hours arterial blood pressure in patients with
      diabetes mellitus but not in control subjects. Plasma adrenomedullin
      concentration in patients with diabetes mellitus treated for hypertension was
      significantly reduced. CONCLUSION: Despite concentration plasma adrenomedullin
      and CGRP modulation by cardioprotective treatment both neuropeptides remained
      involved in regulation of hemodynamic and metabolic parameters in patients with
      Type 2 diabetes mellitus. The low plasma of adrenomedullin in patients with Type
      2 diabetic may be marker of the efficient intervention on cardiovascular risk
      factors.

PMID- 24878982
TI  - The use of panniculectomy in morbidly obese patients undergoing gynecological
      surgery.
AB  - Panniculectomy is a surgical procedure that involves removal of the skin and fat
      excess which facilitates access to the peritoneal cavity. In the paper we present
      three cases of morbidly obese women (BMI: 46.3-59.5) who were treated in the
      Department of Gynecology and Oncological Gynecology in Lodz. One of the patients
      underwent an operation due to the presence of a large cervical myoma. Two another
      women were treated for endometrial cancer. During all of the three procedures
      panniculectomy was the first stage of the operation. 

PMID- 24878983
TI  - Nanocasted synthesis of ordered mesoporous cerium iron mixed oxide and its
      excellent performances for As(V) and Cr(VI) removal from aqueous solutions.
AB  - A novel ordered mesoporous cerium iron mixed oxide (OMCI) with high specific
      surface area and uniform and well-interconnected mesopores was synthesized
      through the nanocasting strategy using mesoporous silica (KIT-6) as a hard
      template. The obtained OMCI was used as an adsorbent to remove As(V) or Cr(VI)
      anions from aqueous solutions, and exhibited excellent performances with the
      maximum adsorption capacities of ~106.2 and ~75.36 mg g(-1) for As(V) and Cr(VI),
      respectively. A mechanism study showed that both Fe and Ce compositions
      participated in the As(V) or Cr(VI) adsorption process, and complex interactions
      were involved, including electrostatic attraction and the replacement of hydroxyl
      groups to form anionic negatively charged inner-sphere surface complexes. The
      OMCI material could be easily regenerated and reused while maintaining high
      adsorption capacities for As(V) and Cr(VI). Owing to their integrated features
      including high specific surface area, uniform and well-interconnected mesopores
      and specific acid-base surface properties, the synthesized OMCI material is
      expected to have good potential for the decontamination of As(V) or Cr(VI)
      polluted waters.

PMID- 24878984
TI  - Supervision of child and adolescent psychiatry fellows.

PMID- 24878985
TI  - Valuing fire planning alternatives in forest restoration: using derived demand to
      integrate economics with ecological restoration.
AB  - Assessing the value of fire planning alternatives is challenging because fire
      affects a wide array of ecosystem, market, and social values. Wildland fire
      management is increasingly used to address forest restoration while pragmatic
      approaches to assessing the value of fire management have yet to be developed.
      Earlier approaches to assessing the value of forest management relied on
      connecting site valuation with management variables. While sound, such analysis
      is too narrow to account for a broad range of ecosystem services. The metric fire
      regime condition class (FRCC) was developed from ecosystem management philosophy,
      but it is entirely biophysical. Its lack of economic information cripples its
      utility to support decision-making. We present a means of defining and assessing
      the deviation of a landscape from its desired fire management condition by re
      framing the fire management problem as one of derived demand. This valued
      deviation establishes a performance metric for wildland fire management. Using a
      case study, we display the deviation across a landscape and sum the deviations to
      produce a summary metric. This summary metric is used to assess the value of
      alternative fire management strategies on improving the fire management condition
      toward its desired state. It enables us to identify which sites are most valuable
      to restore, even when they are in the same fire regime condition class. The case
      study site exemplifies how a wide range of disparate values, such as watershed,
      wildlife, property and timber, can be incorporated into a single landscape
      assessment. The analysis presented here leverages previous research on
      environmental capital value and non-market valuation by integrating ecosystem
      management, restoration, and microeconomics. 

PMID- 24878986
TI  - Sentinel lymph node identification rates and axillary concordance can only be
      accurately determined by comparing 'like with like' injected materials.
AB  - PURPOSE: Despite the accepted status of sentinel lymph node biopsy (SLNB) as the
      standard for axillary staging in breast cancer patients with clinically and
      radiologically negative axillae pre-operatively, there is surprisingly still a
      lack of consensus on the most appropriate site of injection of radioactive tracer
      with or without blue dye. METHODS: We discuss the article by Sadeghi et al.
      "Axillary concordance between superficial and deep sentinel node mapping material
      injections in breast cancer patients: systematic review and meta-analysis of the
      literature." Breast Cancer Res Treat 144(2): 213-222. RESULTS: Whilst in this
      study both comparison arms (superficial and deep injections) were in the same
      patients to ensure comparability of evaluated groups, this does limit the
      conclusions, which can be drawn from this study. It has meant that when comparing
      intra-operative sentinel lymph node (SLN) identification and concordance rates,
      it is not possible to compare 'like with like' at different injection sites (deep
      radioactive tracer vs superficial radioactive tracer; superficial blue dye vs
      deep blue dye). This leads to inaccurate conclusions due to the different
      properties of these materials. CONCLUSIONS: The only way to determine the optimal
      injection site of radioactive tracer and blue dye for SLN identification intra
      operatively and accurate concordance rates is by direct comparisons of 'like with
      like' when it comes to injected materials at different injection sites.

PMID- 24878987
TI  - Determining axillary concordance rate for different injection locations in
      sentinel node mapping of breast cancer: how ambitious can we get?

PMID- 24878988
TI  - Cholesterol biosynthesis inhibitors as potent novel anti-cancer agents:
      suppression of hormone-dependent breast cancer by the oxidosqualene cyclase
      inhibitor RO 48-8071.
AB  - In most human breast cancers, tumor cell proliferation is estrogen dependent.
      Although hormone-responsive tumors initially respond to anti-estrogen therapies,
      most of them eventually develop resistance. Our goal was to identify alternative
      targets that might be regulated to control breast cancer progression.
      Sulforhodamine B assay was used to measure the viability of cultured human breast
      cancer cell lines exposed to various inhibitors. Protein expression in whole-cell
      extracts was determined by Western blotting. BT-474 tumor xenografts in nude mice
      were used for in vivo studies of tumor progression. RO 48-8071 ([4'-[6
      (Allylmethylamino)hexyloxy]-4-bromo-2'-fluorobenzophenone fumarate]; RO), a small
      molecule inhibitor of oxidosqualene cyclase (OSC, a key enzyme in cholesterol
      biosynthesis), potently reduced breast cancer cell viability. In vitro exposure
      of estrogen receptor (ER)-positive human breast cancer cells to pharmacological
      levels of RO or a dose close to the IC50 for OSC (nM) reduced cell viability.
      Administration of RO to mice with BT-474 tumor xenografts prevented tumor growth,
      with no apparent toxicity. RO degraded ERalpha while concomitantly inducing the
      anti-proliferative protein ERbeta. Two other cholesterol-lowering drugs,
      Fluvastatin and Simvastatin, were less effective in reducing breast cancer cell
      viability and were found not to induce ERbeta. ERbeta inhibition or knockdown
      prevented RO-dependent loss of cell viability. Importantly, RO had no effect on
      the viability of normal human mammary cells. RO is a potent inhibitor of hormone
      dependent human breast cancer cell proliferation. The anti-tumor properties of RO
      appear to be in part due to an off-target effect that increases the ratio of
      ERbeta/ERalpha in breast cancer cells. 

PMID- 24878989
TI  - Synergistic anticancer effects of lectin and doxorubicin in breast cancer cells.
AB  - We studied the effects, either combined or alone, of lectin from Korean mistletoe
      (Viscum album var. coloratum agglutinin, VCA) and doxorubicin (DOX) in MCF-7
      (estrogen receptor-positive) and MDA-MB231 (estrogen receptor-negative) human
      breast cancer cells. When VCA and DOX were combined, a strong synergistic effect
      was shown in cell growth inhibition, compared to VCA or DOX treatment alone. In
      quantitative apoptosis studies analyzed by flow cytometry, a combination of two
      agents showed an increase in apoptosis in both cells, compared to agents alone.
      Also, pro-apoptotic proteins including Bax, Bik, and Puma were increased in both
      cells, and the survival factor Bcl-2 was inhibited in MCF-7 cells when drugs were
      combined. Furthermore, VCA combined with DOX mediated S phase arrest, accompanied
      with a decrease of cell number at G0/G1 phase. This suggests that VCA and DOX
      combination may possibly lead to a novel strategy for the treatment of breast
      cancer. 

PMID- 24878990
TI  - MiR-506 inhibits PRRSV replication in MARC-145 cells via CD151.
AB  - Porcine reproductive and respiratory syndrome (PRRS) is one of the most
      economically important diseases of swine, which is caused by PRRS virus (PRRSV).
      CD151, one of PRRSV entry mediators, determines the cell susceptibility for
      PRRSV. Emerging evidence indicates that the host microRNAs (miRNAs) play key
      roles in modulating virus infection and viral pathogenesis. In the present study,
      targeting porcine CD151 miRNAs were identified, and their function during PRRSV
      infection in MARC-145 cells was further verified. We found that miR-506 could
      directly target porcine CD151 3'-UTR mRNA by luciferase reporter assay.
      Overexpression of miR-506 significantly decreased CD151 expression at both mRNA
      and protein levels. Furthermore, overexpression of miR-506 reduced cellular PRRSV
      replication and virus release in MARC-145 cells. Our results suggested that miR
      506 could inhibit PRRSV replication by directly targeting PRRSV receptor of CD151
      in MARC-145 cells. However, the molecular mechanisms of miR-506 and its function
      in vivo need further investigation. 

PMID- 24878991
TI  - Long-chain acylcarnitine content determines the pattern of energy metabolism in
      cardiac mitochondria.
AB  - In the heart, a nutritional state (fed or fasted) is characterized by a unique
      energy metabolism pattern determined by the availability of substrates. Increased
      availability of acylcarnitines has been associated with decreased glucose
      utilization; however, the effects of long-chain acylcarnitines on glucose
      metabolism have not been previously studied. We tested how changes in long-chain
      acylcarnitine content regulate the metabolism of glucose and long-chain fatty
      acids in cardiac mitochondria in fed and fasted states. We examined the
      concentrations of metabolic intermediates in plasma and cardiac tissues under fed
      and fasted states. The effects of substrate availability and their competition
      for energy production at the mitochondrial level were studied in isolated rat
      cardiac mitochondria. The availability of long-chain acylcarnitines in plasma
      reflected their content in cardiac tissue in the fed and fasted states, and
      acylcarnitine content in the heart was fivefold higher in fasted state compared
      to the fed state. In substrate competition experiments, pyruvate and fatty acid
      metabolites effectively competed for the energy production pathway; however, only
      the physiological content of acylcarnitine significantly reduced pyruvate and
      lactate oxidation in mitochondria. The increased availability of long-chain
      acylcarnitine significantly reduced glucose utilization in isolated rat heart
      model and in vivo. Our results demonstrate that changes in long-chain
      acylcarnitine contents could orchestrate the interplay between the metabolism of
      pyruvate-lactate and long-chain fatty acids, and thus determine the pattern of
      energy metabolism in cardiac mitochondria. 

PMID- 24878993
TI  - From Heller to POEM (1914-2014): a 100-year history of surgery for Achalasia.
AB  - BACKGROUND: The year 2014 marks the 100th anniversary of Dr. Heller's description
      of the surgical treatment of patients with achalasia with a cardiomyotomy. This
      100-year-old operation, which is today performed laparoscopically with the
      addition of a partial fundoplication, is considered the treatment of choice for
      patients with achalasia. PURPOSE: Our goals are to revisit the accounts from the
      beginning of the twentieth century in which surgeons tried to identify the
      pathophysiology of achalasia and proposed several operative techniques and to
      follow the evolution of the surgical treatment until modern days.

PMID- 24878992
TI  - CTSB promotes porcine preadipocytes differentiation by degrading fibronectin and
      attenuating the Wnt/beta-catenin signaling pathway.
AB  - The process of preadipocytes differentiation plays a vital role in adipose tissue
      expansion and many factors are involved in this event. Cathepsin B (CTSB),
      secreted from lysosome, has been reported in regulating a variety of
      physiological processes. In this study, we demonstrated CTSB promotes lipid
      accumulation and adipogenic genes expression in porcine primary preadipocytes by
      degrading fibronectin (Fn), a key component of extracellular matrix. Lithium
      chloride (LiCl) is an activator of Wnt/beta-catenin signaling through stabilizing
      beta-catenin. We found that CTSB can relieve the anti-adipogenic effects of LiCl,
      indicating that CTSB could impact Wnt/beta-catenin signaling pathway.
      Interestingly, Fn is an important target gene of Wnt/beta-catenin. So we
      considered that CTSB promote preadipocytes differentiation by suppressing these
      two pathways. 

PMID- 24878994
TI  - Molecular characterization of influenza B virus outbreak on a cruise ship in
      Brazil 2012.
AB  - In February 2012, an outbreak of respiratory illness occurred on the cruise ship
      MSC Armonia in Brazil. A 31-year-old female crew member was hospitalized with
      respiratory failure and subsequently died. To study the etiology of the
      respiratory illness, tissue taken at necropsy from the deceased woman and
      respiratory specimens from thirteen passengers and crew members with respiratory
      symptoms were analyzed. Influenza real-time RT-PCR assays were performed, and the
      full-length hemagglutinin (HA) gene of influenza-positive samples was sequenced.
      Influenza B virus was detected in samples from seven of the individuals,
      suggesting that it was the cause of this respiratory illness outbreak. The
      sequence analysis of the HA gene indicated that the virus was closely related to
      the B/Brisbane/60/2008-like virus, Victoria lineage, a virus contained in the
      2011-12 influenza vaccine for the Southern Hemisphere. Since the recommended
      composition of the influenza vaccine for use during the 2013 season changed, an
      intensive surveillance of viruses circulating worldwide is crucial. Molecular
      analysis is an important tool to characterize the pathogen responsible for an
      outbreak such as this. In addition, laboratory disease surveillance contributes
      to the control measures for vaccine-preventable influenza. 

PMID- 24878995
TI  - Presence of respiratory viruses in equines in Brazil.
AB  - Equines are susceptible to respiratory viruses such as influenza and
      parainfluenza. Respiratory diseases have adversely impacted economies all over
      the world. This study was intended to determine the presence of influenza and
      parainfluenza viruses in unvaccinated horses from some regions of the state of
      Sao Paulo, Brazil. Blood serum collected from 72 equines of different towns in
      this state was tested by hemagglutination inhibition test to detect antibodies
      for both viruses using the corresponding antigens. About 98.6% (71) and 97.2%
      (70) of the equines responded with antibody protective titers (>= 80 HIU/25uL)
      H7N7 and H3N8 subtypes of influenza A viruses, respectively. All horses (72) also
      responded with protective titers (>= 80) HIU/25uL against the parainfluenza
      virus. The difference between mean antibody titers to H7N7 and H3N8 subtypes of
      influenza A viruses was not statistically significant (p > 0.05). The mean titers
      for influenza and parainfluenza viruses, on the other hand, showed a
      statistically significant difference (p < 0.001). These results indicate a better
      antibody response from equines to parainfluenza 3 virus than to the equine
      influenza viruses. No statistically significant differences in the responses
      against H7N7 and H3N8 subtypes of influenza A and parainfluenza 3 viruses were
      observed according to the gender (female, male) or the age (<= 2 to 20 years-old)
      groups. This study provides evidence of the concomitant presence of two subtypes
      of the equine influenza A (H7N7 and H3N8) viruses and the parainfluenza 3 virus
      in equines in Brazil. Thus, it is advisable to vaccinate equines against these
      respiratory viruses. 

PMID- 24878996
TI  - Resistance to amoxicillin, clarithromycin and ciprofloxacin of Helicobacter
      pylori isolated from Southern Brazil patients.
AB  - INTRODUCTION: Helicobacter pylori is a bacteria which infects half the world
      population and is an important cause of gastric cancer. The eradication therapy
      is not always effective because resistance to antimicrobials may occur. The aim
      of this study was to determine the susceptibility profile of H. pylori to
      amoxicillin, clarithromycin and ciprofloxacin in the population of Southern
      Brazil. MATERIAL AND METHODS: Fifty four samples of H. pylori were evaluated. The
      antibiotics susceptibility was determined according to the guidelines of the
      British Society for Antimicrobial Chemotherapy and the Comite de l'Antibiogramme
      de la Societe Francaise de Microbiologie. RESULTS: Six (11.1%) H. pylori isolates
      were resistant to clarithromycin, one (1.9%) to amoxicillin and three (5.5%) to
      ciprofloxacin. These indices of resistance are considered satisfactory and show
      that all of these antibiotics can be used in the empirical therapy. CONCLUSION:
      The antibiotics amoxicillin and clarithromycin are still a good option for first
      line anti-H. pylori treatment in the population of Southern Brazil.

PMID- 24878997
TI  - Seroprevalence of Toxoplasma gondii (Nicole & Manceaux, 1909) and retroviral
      status of client-owned pet cats (Felis catus, Linnaeus, 1758) in Rio de Janeiro,
      Brazil.
AB  - Cats, as definitive host, play an important role in the transmission of
      Toxoplasma gondii. This study aimed to establish the seroprevalence of anti-T.
      gondii immunoglobulins G and M, and determine the frequency of oocysts in the
      feces of the domestic cat population in Rio de Janeiro, Brazil. We also aimed to
      study the association between T. gondii infection and age, sex, breed, lifestyle,
      diet and retroviral infection. A total of 108 cats were included in the study and
      fecal samples of 54 of those cats were obtained. Only 5.6% of the cats were
      seropositive for anti-T. gondii immunoglobulins using the indirect
      hemagglutination test. None of the 54 cats presented oocysts in their fecal
      samples. Although not statistically significant, males, mixed-breed, free-roaming
      and cats aged two years and older were found to be more exposed. Age, lifestyle
      and the use of litter boxes were found to play an important role as risk factors.
      Anemia and retroviral infections were independent of T. gondii infection. No
      antibodies were detected in the majority of cats (94.4%), indicating that those
      cats had never been exposed to the parasite and, therefore, once infected, they
      could present the risk of shedding large numbers of oocysts into the environment.

PMID- 24878998
TI  - The influence of HIV-1 subtypes C, CRF31_BC and B on disease progression and
      initial virologic response to HAART in a Southern Brazilian cohort.
AB  - BACKGROUND: Although most HIV-1 infections in Brazil are due to subtype B,
      Southern Brazil has a high prevalence of subtype C and recombinant forms, such as
      CRF31_BC. This study assessed the impact of viral diversity on clinical
      progression in a cohort of newly diagnosed HIV-positive patients. METHODS: From
      July/2004 to December/2005, 135 HIV-infected patients were recruited. The partial
      pol region was subtyped by phylogeny. A generalized estimating equation (GEE)
      model was used to examine the relationship between viral subtype, CD4+ T cell
      count and viral load levels before antiretroviral therapy. Hazard ratio (Cox
      regression) was used to evaluate factors associated with viral suppression (viral
      load < 50 copies/mL at six months). RESULTS: Main HIV-1 subtypes included B
      (29.4%), C (28.2%), and CRF31_BC (23.5%). Subtypes B and C showed a similar trend
      in CD4+ T cell decline. Comparison of non-B (C and CRF31_BC) and B subtypes
      revealed no significant difference in the proportion of patients with viral
      suppression at six months (week 24). Higher CD4+ T cell count and lower viral
      load were independently associated with viral suppression. CONCLUSION: No
      significant differences were found between subtypes; however, lower viral load
      and higher CD4+ T cell count before therapy were associated with better response.

PMID- 24878999
TI  - Colonization of palm trees by Rhodnius neglectus and household and invasion in an
      urban area, Aracatuba, Sao Paulo State, Brazil.
AB  - The objective of this study is to report on the colonization of palm trees by
      Rhodnius neglectus, its invasion in an urban area, in Aracatuba - Sao Paulo, and
      the control and surveillance measures that have been put in place. Domiciliary
      triatomine searches occurred in apartments upon the inhabitants' notification.
      The collected insects were identified and examined for natural infection and food
      sources with a precipitin test. To search the palm trees, tarps were used to
      cover the floor, and a "Munck" truck equipped with a tree-pruning device was
      utilized. Chemical control was performed with the utilization of a manual
      compression. In 2009, 81 specimens of Rhodnius neglectus were collected from the
      domiciles by the population. The precipitin test revealed a presence of human
      blood in 2.7% of the samples. Entomological studies were carried out in these
      domiciles and in those located within a radius of 200 meters. The search
      performed in the palm trees resulted in the capture of 882 specimens of
      triatomines, negative for tripanosomatids. Mechanical and chemical controls were
      carried out. New searches conducted in the palm trees in the same year resulted
      in the capture of six specimens. The mechanical and chemical controls of the palm
      trees, together with the population's work, proved to be effective, therefore
      preventing these insects' colonization of the city's domiciles. 

PMID- 24879000
TI  - The effect of hookworm infection and urinary schistosomiasis on blood hemoglobin
      concentration of schoolchildren living in northern Mozambique.
AB  - This study aims to assess the association between schistosomiasis and hookworm
      infection with hemoglobin levels of schoolchildren in northern Mozambique.
      Through a cross-sectional survey, 1,015 children from five to 12 years old in the
      provinces of Nampula, Cabo Delgado and Niassa were studied. Hookworm infection
      and urinary schistosomiasis were diagnosed, through Ritchie and filtration
      methods, with a prevalence of 31.3% and 59.1%, respectively. Hemoglobin levels
      were obtained with a portable photometer (Hemocue(r)). The average hemoglobin
      concentration was 10.8 +/- 1.42 g/dL, and 62.1% of the children presented levels
      below 11.5 g/dL, of which 11.8% of the total number of children had hemoglobin
      levels below 9 g/dL. A multiple linear regression analysis demonstrated negative
      interactions between hemoglobin levels and ancylostomiasis, this being restricted
      to the province of Cabo Delgado (beta = -0.55; p < 0.001) where an independent
      interaction between hemoglobin levels and urinary schistosomiasis was also
      observed (beta = -0.35; p = 0.016). The logistical regression model indicated
      that hookworm infection represents a predictor of mild (OR = 1.87; 95% CI = 1.17
      3.00) and moderate/severe anemia (OR = 2.71; 95% CI = 1.50 - 4.89). We concluded
      that, in the province of Cabo Delgado, hookworm and Schistosoma haematobium
      infections negatively influence hemoglobin levels in schoolchildren. Periodical
      deworming should be considered in the region. Health education and improvements
      in sanitary infrastructure could achieve long-term and sustainable reductions in
      soil-transmitted helminthiases and schistosomiasis prevalence rates. 

PMID- 24879002
TI  - A preliminary study on the occurrence of keratinophilic fungi in soils of
      Jamaica.
AB  - This report represents the first study of keratinophilic fungi present in soils
      of Jamaica. Out of the 40 soil samples examined from different habitats, 30 (75%)
      were positive for the presence of keratinophilic fungi, yielding 36 isolates of
      keratinophilic fungi. Microsporum gypseum complex (represented by 16 isolates of
      M. gypseum, and four of M. fulvum) was most frequent, being present in 50% of the
      samples. A very high occurrence of this dermatophyte in Jamaican soil is of
      public health significance. The remaining isolates of keratinophilic fungi were
      represented by Chrysosporium spp (mainly C. indicum and C. tropicum) and
      Sepedonium sp.

PMID- 24879001
TI  - Evidence of Leishmania (Leishmania) infantum infection in dogs from Juiz de Fora,
      Minas Gerais State, Brazil, based on immunochromatographic dual-path platform
      (DPP(r)) and PCR assays.
AB  - In Brazil, domestic dogs are branded as the primary reservoir for zoonotic
      visceral leishmaniasis, due to the clear positive correlation observed between
      human and canine infection rates. This study aimed to carry out a serological
      survey of canine visceral leishmaniasis (CVL) in dogs housed at a public kennel
      in the municipality of Juiz de Fora, Minas Gerais State, Brazil, using the
      immunochromatographic TR DPP(r) CVL rapid test. Additionally, conventional and/or
      real time PCR assay was used to detect and confirm L. infantum infection in the
      DPP positive dogs only. Of the 400 dogs studied, most did not present clinical
      signs for CVL (p < 0.05), and fifteen (3.8%) were seropositive in the DPP test.
      There was no statistically significant difference between the DPP seropositive
      dogs and the clinical signs of the disease (p > 0.05). Both conventional and real
      time PCR tests confirmed L. infantum infection in nine (75.0%) of the twelve DPP
      seropositive dogs that remained alive during the follow-up period. This study is
      the first seroepidemiologic survey of CVL held in the city of Juiz de Fora, and
      the results reinforce the idea that this disease is currently in a process of
      expansion and urbanization in Brazil. Furthermore, this study highlights the use
      of the DPP test as an alternative for diagnosing CVL in large and mid-sized
      cities, due to its ease of implementation. 

PMID- 24879003
TI  - Spatial distribution of Lymnaeidae (Mollusca, Basommatophora), intermediate host
      of Fasciola hepatica Linnaeus, 1758 (Trematoda, Digenea) in Brazil.
AB  - Snails of the family Lymnaeidae act as intermediate hosts in the biological cycle
      of Fasciola hepatica, which is a biological agent of fasciolosis, a parasitic
      disease of medical importance for humans and animals. The present work aimed to
      update and map the spatial distribution of the intermediate host snails of F.
      hepatica in Brazil. Data on the distribution of lymnaeids species were compiled
      from the Collection of Medical Malacology (Fiocruz-CMM, CPqRR), Collection of
      Malacology (MZUSP), "SpeciesLink" (CRIA) network and through systematic surveys
      in the literature. Our maps of the distribution of lymnaeids show that
      Pseudosuccinea columella is the most common species and it is widespread in the
      South and Southeast with few records in the Midwest, North and Northeast regions.
      The distribution of the Galba viatrix, G. cubensis and G. truncatula showed a few
      records in the South and Southeast regions, they were not reported for the
      Midwest, North and Northeast. In addition, in the South region there are a few
      records for G. viatrix and one occurrence of Lymnaea rupestris. Our findings
      resulted in the first map of the spatial distribution of Lymnaeidae species in
      Brazil which might be useful to better understand the fasciolosis distribution
      and delineate priority areas for control interventions. 

PMID- 24879004
TI  - Neurocysticercosis in children presenting with afebrile seizure: clinical
      profile, imaging and serodiagnosis.
AB  - Neurocysticercosis (NCC) is one of the major causes of childhood seizures in
      developing countries including India and Latin America. In this study
      neurological pediatric cases presenting with afebrile seizures were screened for
      anti-Cysticercus antibodies (IgG) in their sera in order to estimate the possible
      burden of cysticercal etiology. The study included a total of 61 pediatric
      afebrile seizure subjects (aged one to 15 years old); there was a male
      predominance. All the sera were tested using a pre-evaluated commercially
      procured IgG-ELISA kit (UB-Magiwell Cysticercosis Kit TM). Anti-Cysticercus
      antibody in serum was positive in 23 of 61 (37.7%) cases. The majority of cases
      with a positive ELISA test presented with generalized seizure (52.17%), followed
      by complex partial seizure (26.08%), and simple partial seizure (21.73%).
      Headaches were the major complaint (73.91%). Other presentations were vomiting
      (47.82%), pallor (34.78%), altered sensorium (26.08%), and muscle weakness
      (13.04%). There was one hemiparesis case diagnosed to be NCC. In this study one
      child without any significant findings on imaging was also found to be positive
      by serology. There was a statistically significant association found between the
      cases with multiple lesions on the brain and the ELISA-positivity (p = 0.017).
      Overall positivity of the ELISA showed a potential cysticercal etiology. Hence,
      neurocysticercosis should be suspected in every child presenting with afebrile
      seizure especially with a radio-imaging supportive diagnosis in tropical
      developing countries or areas endemic for taeniasis/cysticercosis. 

PMID- 24879005
TI  - Dose response effect of Paracoccidioides brasiliensis in an experimental model of
      arthritis.
AB  - Paracoccidioidomycosis (PCM) is caused by the dimorphic fungus Paracoccidioides
      brasiliensis (Pb) and corresponds to prevalent systemic mycosis in Latin America.
      The aim of the present work was to evaluate the dose response effect of the
      fungal yeast phase for the standardization of an experimental model of septic
      arthritis. The experiments were performed with groups of 14 rats that received
      doses of 103, 104 or 105 P. brasiliensis (Pb18) cells. The fungi were injected in
      50 uL of phosphate-buffered saline (PBS) directly into the knee joints of the
      animals. The following parameters were analyzed in this work: the formation of
      swelling in knees infused with yeast cells and the radiological and
      anatomopathological alterations, besides antibody titer by ELISA. After 15 days
      of infection, signs of inflammation were evident. At 45 days, some features of
      damage and necrosis were observed in the articular cartilage. The systemic
      dissemination of the fungus was observed in 11% of the inoculated animals, and it
      was concluded that the experimental model is able to mimic articular PCM in
      humans and that the dose of 105 yeast cells can be used as standard in this
      model. 

PMID- 24879006
TI  - Use of lopinavir/ritonavir associated with ergotamine resulting in foot
      amputation: brief communication.
AB  - A 32-year-old female, was diagnosed in 2004 with a C1 HIV1 infection, using
      zidovudine/lamivudine 300/150 mg BID and lopinavir/ritonavir 400/100 mg BID, in
      addition to prophylaxis with trimethoprim-sulfamethoxazole 800/160 mg QD, but no
      prophylaxis with macrolide antibiotics. The patient presented with a severe
      headache and was prescribed two capsules of the anti-migraine drug OrmigreinTM,
      which contained ergotamine tartrate 1 mg, caffeine 100 mg, paracetamol 220 mg,
      hyoscyamine sulfate 87.5 mcg, and atropine sulfate 12.5 mcg. Afterwards she was
      prescribed one capsule of Ormigrein every 30 minutes for a total of six capsules
      a day. The patient took the medication as prescribed but developed a pain in her
      left ankle three days later, which evolved to the need for amputation. 

PMID- 24879008
TI  - Expansion of visceral leishmaniasis in the State of Rio de Janeiro, Brazil:
      report of the first autochthonous case in the municipality of Volta Redonda and
      the difficulty of diagnosis.
AB  - Visceral Leishmaniasis has been showing remarkable epidemiological changes in
      recent decades, with marked expansion and an emergence of cases in urban areas of
      the North, Southeast and Midwest regions of Brazil. The Kala-azar cases reported
      here, despite being very characteristic, presented a great difficulty of
      diagnosis, because the disease is not endemic in Volta Redonda. The child
      underwent two hospitalizations in different hospitals, but got the correct
      diagnosis only after 11 months of symptom onset. In this report we discuss the
      main differential diagnoses and call attention to the suspected symptoms of
      visceral leishmaniasis in patients with prolonged fever, hepatosplenomegaly and
      pancytopenia, even in areas not traditionally endemic for the disease. 

PMID- 24879007
TI  - Fatal outcome of infection by dengue 4 in a patient with thrombocytopenic purpura
      as a comorbid condition in Brazil.
AB  - Dengue is currently a major public-health problem. Dengue virus (DENV) is
      classified into four distinct serotypes, DENV 1-4. After 28 years of absence,
      DENV-4 was again detected in Brazil in 2010 in Roraima State, and one year later,
      the virus was identified in the northern Brazilian states of Amazonas and Para,
      followed by Rio de Janeiro and Sao Paulo. In Minas Gerais, the first confirmed
      case of DENV-4 occurred in the municipality of Frutal in 2011 and has now been
      isolated from a growing number of patients. Although DENV-2 is associated with
      the highest risk of severe forms of the disease and death due to the infection,
      DENV-4 has also been associated with severe forms of the disease and an
      increasing risk of hemorrhagic manifestations. Herein, the first fatal case of
      confirmed DENV-4 in Brazil is reported. The patient was an 11-year-old girl from
      the municipality of Montes Claros in northern Minas Gerais State, Brazil. She had
      idiopathic thrombocytopenic purpura as a comorbid condition and presented with a
      fulminant course of infection, leading to death due to hemorrhagic complications.
      Diagnosis was confirmed by detection of Dengue-specific antibodies using IgM
      capture enzyme-linked immunosorbent assay and semi-nested RT-PCR. Primary care
      physicians and other health-care providers should bear in mind that DENV-4 can
      also result in severe forms of the disease and lead to hemorrhagic complications
      and death, mainly when dengue infection is associated with coexisting conditions.

PMID- 24879009
TI  - Should school-age children not attending school and adults aged 20-44 years be
      considered high-risk group for bacillary dysentery infection in Guangzhou, China?
      A review of 4,775 bacillary dysentery cases.

PMID- 24879010
TI  - Whole genome analyses of marine fish pathogenic isolate, Mycobacterium sp.
      012931.
AB  - Mycobacterium is a genus within the order Actinomycetales that comprises of a
      large number of well-characterized species, several of which includes pathogens
      known to cause serious disease in human and animal. Here, we report the whole
      genome sequence of Mycobacterium sp. strain 012931 isolated from the marine fish,
      yellowtail (Seriola quinqueradiata). Mycobacterium sp. 012931 is a fish pathogen
      causing serious damage to aquaculture farms in Japan. DNA dot plot analysis
      showed that Mycobacterium sp. 012931 was more closely related to Mycobacterium
      marinum when compared across several Mycobacterium species. However, little
      conservation of the gene order was observed between Mycobacterium sp. 012931 and
      M. marinum genome. The annotated 5,464 genes of Mycobacterium sp. 012931 was
      classified into 26 subsystems. The insertion/deletion gene analysis shows
      Mycobacterium sp. 012931 had 643 unique genes that were not found in the M.
      marinum strains. In the virulence, disease, and defense subsystem, both insertion
      and deletion genes of Mycobacterium sp. 012931 were associated with the PPE gene
      cluster of Mycobacteria. Of seven plcB genes in Mycobacterium sp. 012931, plcB_2
      and plcB_3 showed low identities with those of M. marinum strains. Therefore,
      Mycobacterium sp. 012931 has differences on genetic and virulence from M. marinum
      and may induce different interaction mechanisms between host and pathogen. 

PMID- 24879011
TI  - Structure of a sulfated xylofucan from the brown alga Punctaria plantaginea.
AB  - A polysaccharide composed of L-fucose, D-xylose, and sulfate in a molar
      proportion of about 5:2:3 was isolated from the brown alga Punctaria plantaginea.
      Polysaccharide structure was elucidated by methylation analysis, Smith
      degradation, as well as by 1D and 2D NMR spectroscopy. The polysaccharide was
      shown to contain a backbone of 3-linked alpha-L-fucopyranose residues, about two
      thirds of which are sulfated at O-2 forming trisaccharide repeating units ->3)
      alpha-L-Fucp2S-(1->3)-alpha-L-Fucp2S-(1->3)-alpha-L-Fucp-(1->. This structural
      regularity is masked by random distribution of non-sulfated beta-D-Xylp residues
      attached to position 4 of the backbone. The polysaccharide is a new
      representative of a complex 'fucoidan' family of sulfated polysaccharides of
      brown seaweeds.

PMID- 24879012
TI  - Access to bifunctionalized biomolecular platforms using oxime ligation.
AB  - This paper describes an efficient oxime ligation strategy to prepare multivalent
      conjugates wherein peptides alone or in combination with carbohydrate or oxime
      groups were coupled to a cyclopeptide scaffold. To demonstrate the versatility of
      this approach, two classes of conjugates have been prepared. In one class, we
      attached two or four peptide sequences to the cyclopeptide core together with
      free oxime groups, while the second class contains an additional substitution
      with four or two monosaccharides. The well-defined structure of these conjugates
      was confirmed by high-resolution mass spectrometry. 

PMID- 24879014
TI  - Antiparasitic effect of wild rue (Peganum harmala L.) against experimentally
      induced coccidiosis in broiler chicks.
AB  - Organic farming of poultry has increased in recent years as the prophylactic use
      of antibiotics has come into disfavor. This study was conducted to explore the
      antiparasitic effect of a methanolic extract of Peganum harmala in broilers
      challenged with coccidiosis. For this purpose, 200 1-week-old broiler chicks were
      divided into five treatments: negative control (basal diet, Ph-0/NC), positive
      control (basal diet with coccidiosis challenge, Ph-0/C), and three groups
      challenged with coccidiosis and supplemented with P. harmala at the rate of 200
      mg L(-1) (Ph-200), 250 mg L(-1) (Ph-250), and 300 mg L(-1) (Ph-300) drinking
      water. Each group had three replicates of ten chicks each. Challenge with
      standard dose of the larvae of coccidiosis and supplementation of P. harmala were
      initiated on day 14 until 35 days of age. As expected, the results revealed that
      weight gain, feed intake, and feed conversion ratio (FCR) were depressed
      significantly in Ph-0 group with significant mortality percentage. Weight gain,
      total body weight, and FCR increased linearly with increasing dose of P. harmala
      with the exception of feed intake. The growth and feed efficiency of Ph-0/NC was
      better in Ph-0/NC compared to that in Ph-0/C and comparable to that in P. harmala
      treated birds. Similarly, mean ooccytes per gram (OPG) decreased linearly (P <
      0.05) in supplemented groups compared to that in Ph-0/C. Histological evidences
      showed that cecal lesion and leucocyte infiltration decreased markedly in
      supplemented groups of P. harmala specifically the Ph-300 group compared to those
      in Ph-0/C. From the present experiment, we concluded the anticoccidial effect of
      P. harmala in broiler chicks.

PMID- 24879015
TI  - Factors associated with the prevalence and pathology of Calodium hepaticum and C.
      splenaecum in periurban micromammals.
AB  - Calodium hepaticum (syn. Capillaria hepatica) and Calodium splenaecum (syn.
      Capillaria splenaecum) are nematodes that infect the liver and spleen,
      respectively, of mammals. While the host range, distribution, pathology and
      zoonotic potential of C. hepaticum are well known, very little is known about C.
      splenaecum. The observed prevalence of these two parasites, the factors
      associated with prevalence, and the lesions resulting in the different host
      species were studied in 408 micromammals captured in two periurban areas of
      Barcelona (NE Spain) from 2011 to 2013. C. hepaticum was found in 4% of 322 wood
      mice (Apodemus sylvaticus) (with local prevalence up to 16%) and 1 of 2 Norwegian
      rats (Rattus norvegicus). C. splenaecum was found in 10 % of 38 greater white
      toothed shrew (Crocidura russula) (local prevalence up to 30%). Neither parasite
      was detected in 29 Algerian mice (Mus spretus) and 17 black rats (Rattus rattus).
      Prevalence of C. hepaticum was significantly higher in wood mice captured in
      natural areas (6.4%) than those from residential areas (0%), and infected mice
      were in better body condition. No differences in prevalence were found among age
      and sex groups, years and seasons. Lesions of hepatic capillariasis in wood mice
      consisted mainly of mild to moderate multifocal granulomas around degenerating
      adult parasites and/or eggs, while lesions seen in a rat consisted of multifocal
      granulomatous hepatitis and bridging fibrosis extending from the necrotic areas
      caused by the parasites. Splenic lesions found in shrews due to C. splenaecum,
      representing the first histological description of this parasite, were single
      nodules that corresponded to finely encapsulated clusters of eggs with adult
      parasites.

PMID- 24879013
TI  - Olfactory deficits in an alpha-synuclein fly model of Parkinson's disease.
AB  - Parkinson's disease (PD) is the most common motor neurodegenerative disorder.
      Olfactory dysfunction is a prevalent feature of PD. It often precedes motor
      symptoms by several years and is used in assisting PD diagnosis. However, the
      cellular and molecular bases of olfactory dysfunction in PD are not known. The
      fruit fly Drosophila melanogaster, expressing human alpha-synuclein protein or
      its mutant, A30P, captures several hallmarks of PD and has been successfully used
      to model PD in numerous studies. First, we report olfactory deficits in fly
      expressing A30P (A30P), showing deficits in two out of three olfactory
      modalities, tested--olfactory acuity and odor discrimination. The remaining third
      modality is odor identification/naming. Second, oxidative stress is an important
      environmental risk factor of PD. We show that oxidative stress exacerbated the
      two affected olfactory modalities in younger A30P flies. Third, different
      olfactory receptor neurons are activated differentially by different odors in
      flies. In a separate experiment, we show that the odor discrimination deficit in
      A30P flies is general and not restricted to a specific class of chemical
      structure. Lastly, by restricting A30P expression to dopamine, serotonin or
      olfactory receptor neurons, we show that A30P expression in dopamine neurons is
      necessary for development of both acuity and discrimination deficits, while
      serotonin and olfactory receptor neurons appeared not involved. Our data
      demonstrate olfactory deficits in a synuclein fly PD model for exploring
      olfactory pathology and physiology, and for monitoring PD progression and
      treatment.

PMID- 24879018
TI  - Impact of age, performance and athletic event on injury rates in master athletics
      - first results from an ongoing prospective study.
AB  - OBJECTIVES: Recent studies have identified rates of injuries in young elite
      athletes during major athletic events. However, no such data exist on master
      athletes. The aim of this study was to assess incidence and types of injuries
      during the 2012 European Veteran Athletics Championships as a function of age,
      performance and athletic discipline. METHODS: Report forms were used to identify
      injured athletes and injury types. Analysis included age (grouped in five-year
      bands beginning at age 35 years), athletic event, and age-graded performance.
      RESULTS: Of the 3154 athletes (53.2 years (SD 12.3)) that participated in the
      championships (1004 (31.8%) women, 2150 (68.2%) men), 76 were registered as
      injured; 2.8% of the female (29), 2.2% of the male (47) athletes. There were no
      fractures. One injury required operative treatment (Achilles tendon rupture).
      Injury rates were significantly higher in the sprint/middle distance/jumps than
      the throws, long distance and decathlon/heptathlon groups (X(2) (3)=16.187,
      P=0.001). There was no significant interrelationship with age (X(2) (12)=6.495,
      P=0.889) or age-graded performance (X(2) (3)=3.563, P=0.313). CONCLUSIONS: The
      results suggest that healthy master athletes have a low risk of injury that does
      not increase with age or performance.

PMID- 24879016
TI  - HIF1alpha and HIF2alpha exert distinct nutrient preferences in renal cells.
AB  - BACKGROUND: Hypoxia Inducible Factors (HIF1alpha and HIF2alpha) are commonly
      stabilized and play key roles related to cell growth and metabolic programming in
      clear cell renal cell carcinoma. The relationship of these factors to discretely
      alter cell metabolic activities has largely been described in cancer cells, or in
      hypoxic conditions, where other confounding factors undoubtedly compete. These
      transcription factors and their specific roles in promoting cancer metabolic
      phenotypes from the earliest stages are poorly understood in pre-malignant cells.
      METHODS: We undertook an analysis of SV40-transformed primary kidney epithelial
      cells derived from newborn mice genetically engineered to express a stabilized
      HIF1alpha or HIF2alpha transgene. We examined the metabolic profile in relation
      to each gene. RESULTS: Although the cells proliferated similarly, the metabolic
      profile of each genotype of cell was markedly different and correlated with
      altered gene expression of factors influencing components of metabolic signaling.
      HIF1alpha promoted high levels of glycolysis as well as increased oxidative
      phosphorylation in complete media, but oxidative phosphorylation was suppressed
      when supplied with single carbon source media. HIF2alpha, in contrast, supported
      oxidative phosphorylation in complete media or single glucose carbon source, but
      these cells were not responsive to glutamine nutrient sources. This finding
      correlates to HIF2alpha-specific induction of Glul, effectively reducing
      glutamine utilization by limiting the glutamate pool, and knockdown of Glul
      allows these cells to perform oxidative phosphorylation in glutamine media.
      CONCLUSION: HIF1alpha and HIF2alpha support highly divergent patterns of kidney
      epithelial cell metabolic phenotype. Expression of these factors ultimately
      alters the nutrient resource utilization and energy generation strategy in the
      setting of complete or limiting nutrients.

PMID- 24879019
TI  - Validity of an accelerometer as a vertical ground reaction force measuring device
      in healthy children and adolescents and in children and adolescents with
      osteogenesis imperfecta type I.
AB  - INTRODUCTION: Vertical ground reaction forces (vGRFs) are closely related to bone
      strength and development. It is therefore relevant to assess these forces in bone
      disorders accompanied with muscle weakness such as in osteogenesis imperfecta
      type I (OI type I). The purpose of the present study was to assess the validity
      of vGRFs derived from an accelerometer. METHODS: Fourteen children and
      adolescents with a diagnosis of OI type I (age range: 7 to 21; mean age [SD]:
      14.1 [4.8] years; 5 males) and fourteen healthy controls (age range: 6 to 21;
      mean age [SD]: 12.5 [4.2] years; 5 males) performed three repetitions of five
      different jump and rise tests on a ground reaction force plate. Jumps and rises
      outcomes were measured simultaneously with the ground reaction force plate and an
      accelerometer. RESULTS: Pearson correlation coefficients were over 0.96 (p<0.001)
      for the five tests. The limits of agreement represented between 17 and 31% of the
      average peak force measured by both devices. The accelerometer is a promising
      tool to assess ground reaction forces in everyday life settings and has been
      shown to be sufficiently sensitive to detect muscular weakness in children and
      adolescent with OI type I.

PMID- 24879017
TI  - Rif1 regulates initiation timing of late replication origins throughout the S.
      cerevisiae genome.
AB  - Chromosomal DNA replication involves the coordinated activity of hundreds to
      thousands of replication origins. Individual replication origins are subject to
      epigenetic regulation of their activity during S-phase, resulting in differential
      efficiencies and timings of replication initiation during S-phase. This
      regulation is thought to involve chromatin structure and organization into timing
      domains with differential ability to recruit limiting replication factors. Rif1
      has recently been identified as a genome-wide regulator of replication timing in
      fission yeast and in mammalian cells. However, previous studies in budding yeast
      have suggested that Rif1's role in controlling replication timing may be limited
      to subtelomeric domains and derives from its established role in telomere length
      regulation. We have analyzed replication timing by analyzing BrdU incorporation
      genome-wide, and report that Rif1 regulates the timing of late/dormant
      replication origins throughout the S. cerevisiae genome. Analysis of pfa4Delta
      cells, which are defective in palmitoylation and membrane association of Rif1,
      suggests that replication timing regulation by Rif1 is independent of its role in
      localizing telomeres to the nuclear periphery. Intra-S checkpoint signaling is
      intact in rif1Delta cells, and checkpoint-defective mec1Delta cells do not
      comparably deregulate replication timing, together indicating that Rif1 regulates
      replication timing through a mechanism independent of this checkpoint. Our
      results indicate that the Rif1 mechanism regulates origin timing irrespective of
      proximity to a chromosome end, and suggest instead that telomere sequences merely
      provide abundant binding sites for proteins that recruit Rif1. Still, the
      abundance of Rif1 binding in telomeric domains may facilitate Rif1-mediated
      repression of non-telomeric origins that are more distal from centromeres. 

PMID- 24879020
TI  - Galnon, a galanin receptor agonist, improves intrinsic cortical bone tissue
      properties but exacerbates bone loss in an ovariectomised rat model.
AB  - OBJECTIVES: Previous studies have shown galanin (GAL) injections onto mouse
      calvaria increased bone thickness and osteoblast number. This study investigated
      the effects of the GAL receptor agonist galnon on bone loss using the
      ovariectomised (OVX) rat model. METHODS: OVX rats were treated with either
      vehicle or galnon for 6 weeks via mini-osmotic pumps. Plasma osteocalcin
      concentrations, osseous cell gene expression, morphological and biomechanical
      properties of the skeleton were compared between the two groups. RESULTS:
      Treatment with galnon increased RANKL:OPG gene ratio (p<0.001) plus expression of
      TNF-alpha (p<0.05) and cathepsin K (p<0.05). MUCT analyses revealed galnon
      treated OVX animals had reduced trabecular and cortical morphology compared to
      control animals. Biomechanically, galnon OVX animals required similar peak force
      to failure to that of control OVX animals although galnon treatment did enhance
      the mechanical properties of Young's modulus and ultimate tensile stress.
      CONCLUSIONS: Our research suggests that galnon, a GAL receptor agonist, may
      enhance osteoclastic bone resorption in OVX rats. Although galnon reduced bone
      volume, biomechanical testing revealed that bone of galnon-treated animals was
      mechanically superior per unit area. Taken together, galnon simultaneously
      improves the intrinsic quality of cortical bone whilst stimulating osteoclastic
      activity in the OVX rat model.

PMID- 24879021
TI  - Cholinergic nerve fibers in bone defects of a rat osteoporosis model and their
      regulation by implantation of bone substitution materials.
AB  - OBJECTIVES: Bone is innervated by autonomic nervous system that consists of
      sympathetic and parasympathetic nerves that were recently identified in bone.
      Thus we asked whether parasympathetic nerves occur in bone defects and at the
      interface of substitution materials that were implanted for stabilization and
      improvement of healing in an osteoporosis animal model. METHODS: Osteoporosis was
      induced in rats by ovariectomy and deficiency diet. A wedge-shaped osteotomy was
      performed in the metaphyseal area of femur. Eight different implants were
      inserted that were based on calcium phosphate cement, iron, silica-mineralized
      collagen, and modifications with strontium. Nerves were identified by
      immunohistochemistry with antibodies against vesicular acetylcholine transporter
      (VAChT), tyrosine hydroxylase (TH) and protein gene product 9.5 (PGP 9.5) as
      neuronal marker. RESULTS: Cholinergic nerves identified with VAChT immunostaining
      were detected in defects filled with granulation tissue and in surrounding mast
      cells. No immunolabeling of cholinergic nerves was found after implantation. The
      general presence of nerves was reduced after implantation as shown by PGP 9.5.
      Sympathetic nerves identified by TH immunolabeling were increased in strontium
      functionalized materials. CONCLUSION: Since cholinergic innervation was
      diminished after implantation a further increase in the compatibility of
      substitution materials to nerves could improve defect healing especially in
      osteoporotic bone.

PMID- 24879022
TI  - Increased bone mineral density at the hypoxia prone site of the juxta-articular
      metacarpal bone in patients with limited systemic sclerosis: a cross-sectional
      study.
AB  - OBJECTIVES: Low levels of oxygen has been shown to be involved in the induction
      of osteogenesis, particularly in bone repair. It is unknown whether hypoxia leads
      to osteogenesis at the hypoxia prone skeletal sites in limited systemic
      sclerosis. This study determined the total and trabecular volumetric bone mineral
      density (vBMD) at the hypoxia prone site of the juxta-articular metacarpal bone.
      METHODS: In this cross-sectional study, female patients with limited systemic
      sclerosis were included and compared to healthy controls. Peripheral quantitative
      computed tomography was used to measure cross-sectional area, total vBMD, and
      trabecular vBMD at the radius, the tibia and the third metacarpal bone. Disease
      severity was assessed by the modified Rodnan Skin Score. RESULTS: Twenty
      consecutive patients were included in the sclerosis group and 20 in the control
      group. Mean age was 60 years (range 52-68 years), and mean disease duration was
      45 months (range 4-156 months). Age, height, and weight were comparable between
      the groups. The mean modified Rodnan Skin Score was 1.78 (range 0 to 8). The
      sclerosis group showed both higher total and trabecular vBMD at the distal
      metacarpal bone (p=0.05 and 0.04, respectively). vBMD of the tibia and radius did
      not differ in both groups. CONCLUSIONS: vBMD at the juxta-articular metacarpal
      bone in patients with limited systemic sclerosis is increased, possibly due to an
      alteration in local bone metabolism and hypoxia induced local osteogenesis.

PMID- 24879024
TI  - Biomechanical analysis of fracture risk associated with tibia deformity in
      children with osteogenesis imperfecta: a finite element analysis.
AB  - OBJECTIVES: Osteogenesis imperfecta (OI) frequently leads to long-bone bowing
      requiring a surgical intervention in severe cases to avoid subsequent fractures.
      However, there are no objective criteria to decide when to perform such
      intervention. The objective is to develop a finite element model to predict the
      risk of tibial fracture associated with tibia deformity in patients with OI.
      METHODS: A comprehensive FE model of the tibia was adapted to match bi-planar
      radiographs of a 7 year-old girl with OI. Ten additional models with different
      deformed geometries (from 2 degrees  to 24 degrees ) were created and the elasto
      plastic mechanical properties were adapted to reflect OI conditions. Loads were
      obtained from mechanography of two-legged hopping. Two additional impact cases
      (lateral and torsion) were also simulated. Principal strain levels were used to
      define a risk criterion. RESULTS: Fracture risks for the two-legged hopping load
      case remained low and constant until tibia bowing reached 15 degrees  and 16
      degrees  in sagittal and coronal planes respectively. Fracture risks for lateral
      and torsion impact were equivalent whatever the level of tibial bowing.
      CONCLUSIONS: The finite element model of OI tibia provides an objective means of
      assessing the necessity of surgical intervention for a given level of tibia
      bowing in OI-affected children.

PMID- 24879025
TI  - Effects of whole-body vibration with an unstable surface on muscle activation.
AB  - The current study examined the effects of using an unstable surface during whole
      body vibration (WBV) exercise on leg and trunk muscle activity during a static
      semi-squat. Twenty-eight recreationally active university students completed 4
      different test conditions: 1) stable surface with no WBV; 2) unstable surface
      with no WBV; 3) unstable surface with 30 Hz WBV low amplitude; and 4) unstable
      surface with 50 Hz WBV low amplitude. Surface electromyography (sEMG) was
      measured for the gastrocnemius medialis (GM), vastus medialis oblique (VMO),
      vastus lateralis (VL), rectus abdominis (RA), and multifidus (MF) muscles.
      Normalized to the stable condition, WBV at 30 Hz and an unstable surface
      increased EMG in the GM vs the unstable and stable surfaces (~35%; p<0.05). VMO
      EMG decreased in the unstable vs stable condition (~20%), WBV at 30 Hz and an
      unstable surface increased EMG vs all other conditions (~20-40%; p<0.05). MF EMG
      increased with WBV at 30 Hz (25%; p<0.05) vs the stable condition but not vs all
      other conditions. Using an unstable surface during WBV exposure increases EMG of
      muscles in the lower extremities and trunk suggesting the combination of an
      unstable surface combined with WBV may be an effective modality to further
      increase EMG. 

PMID- 24879023
TI  - Muscle density predicts changes in bone density and strength: a prospective study
      in girls.
AB  - OBJECTIVE: We sought to determine whether muscle density, an index of skeletal
      muscle fat content, was predictive of 2-year changes in weight-bearing bone
      parameters in young girls. METHODS: Two-year prospective data from 248 girls,
      aged 8-13 years at baseline. Peripheral quantitative computed tomography was used
      to measure changes in bone strength indices (bone strength index [BSI,
      mg(2)/mm(4)] and strength-strain index [SSIp, mm(3)]) and volumetric bone mineral
      density [vBMD, mg/cm(3)] at distal metaphyseal and diaphyseal regions of the
      femur and tibia, as well as calf and thigh muscle density (mg/cm(3)), and muscle
      cross-sectional area (MCSA, mm(2)), indices of skeletal muscle fat content and
      muscle force production, respectively. RESULTS: After controlling for potential
      confounders, greater gains in femur BSI (44%, P<0.002), total femur vBMD (114%,
      P<0.04) and femur trabecular vBMD (306%, P<0.002) occurred in girls in the lowest
      versus the highest groups of baseline thigh muscle density. Greater gains in
      tibial BSI (25%, P<0.03) and trabecular vBMD (190%, P<0.002) were also observed
      in the lowest versus the highest baseline calf muscle density groups. CONCLUSION:
      Baseline muscle density is a significant predictor of changes in bone density and
      bone strength in young girls during a period of rapid skeletal development.

PMID- 24879026
TI  - Electrical stimulation of denervated rat skeletal muscle retards trabecular bone
      loss in early stages of disuse musculoskeletal atrophy.
AB  - OBJECTIVES: We aimed to determine the intensity of muscle stimulation required to
      prevent structural failure as well as bone and skeletal muscle loss after
      denervation-induced disuse. METHODS: Seven-week-old rats (weight, 198-225 g) were
      randomly assigned to age-matched groups comprising control (CON), sciatic nerve
      denervation (DN) or direct electrical stimulation (ES) one day later [after
      denervation] with 4, 8 and 16 mA at 10 Hz for 30 min/day, six days/week, for one
      or three weeks. Bone architecture and mean osteoid thickness in histologically
      stained tibial sections and tension in tibialis anterior muscles were assessed at
      one and three weeks after denervation. RESULTS: Direct ES with 16 mA generated 23
      30% maximal contraction force. Denervation significantly decreased trabecular
      bone volume fraction, thickness and number, connectivity density and increased
      trabecular separation in the DN group at weeks one and three. Osteoid thickness
      was significantly greater in the ES16 group at week one than in the DN and other
      ES groups. Trabecular bone volume significantly correlated with muscle weight.
      CONCLUSIONS: Relatively low-level muscle contraction induced by low-frequency,
      high-intensity electrical muscle stimulation delayed trabecular bone loss during
      the early stages (one week after DN) of musculoskeletal atrophy due to disuse.

PMID- 24879027
TI  - Loss of bone strength in response to exercise-induced weight loss in obese
      postmenopausal women: results from a pilot study.
AB  - OBJECTIVE: Exercise-induced weight loss (WL) can lead to decreased areal bone
      mineral density (aBMD). It is unknown whether this translates into decreased
      volumetric BMD (vBMD) or bone strength. The purpose of this pilot study was to
      determine whether exercise-induced WL results in decreased vBMD and bone strength
      in postmenopausal women. METHODS: Fourteen subjects participated in a 4-month
      endurance exercise WL intervention. A weight stable (WS) control group (n=10) was
      followed for 4 months. Proximal femur aBMD was measured by DXA. Femoral neck vBMD
      and estimates of bone strength (cross-sectional moment of inertia (CSMI) and
      section modulus (SM)) were measured by quantitative CT. RESULTS: Women were
      54.6+/-2.4 years, BMI 32.1+/-5.9 kg/m(2) and 54.4+/-2.9 years, BMI 27.9+/-3.6
      kg/m(2) in the WL and WS groups, respectively. The WL group lost 3.0+/-2.6 kg
      which was predominately fat mass. There was a significant decrease in SMmax.
      Changes in CSMImax and total hip aBMD were not significant. Total hip vBMD did
      not decrease significantly in response to WL. There were no significant changes
      in the WS group. CONCLUSIONS: WL may lead to decreased bone strength before
      changes in BMD are detected. Further studies are needed to determine whether bone
      targeted exercise can preserve bone strength during WL.

PMID- 24879028
TI  - Physical activity completed when young has residual bone benefits at 94 years of
      age: a within-subject controlled case study.
AB  - Physical activity is recommended for skeletal health because bones adapt to
      mechanical loading. The young skeleton shows greatest plasticity to physical
      activity-related mechanical loads, but bones are most at risk of failure later in
      life. The discrepancy raises the question of whether the skeletal benefits of
      physical activity completed when young persist with aging. Here we present a
      unique case wherein the cortical bone benefit of physical activity completed over
      five decades earlier could be established within an individual aged in their
      tenth decade of life. Specifically, we compared bone properties at the midshaft
      humerus between the throwing and nonthrowing arms of a 94-year-old former Major
      League Baseball player who ceased throwing 55 years earlier. By performing
      analyses within-subject, the long-term skeletal benefit of physical activity
      completed when young could be assessed independent of inherited and systemic
      traits. Also, as the subject threw left-handed during his throwing career, but
      was right-hand dominant in all other activities throughout life, any lasting
      skeletal benefits in favor of the throwing arm could not be attributable to
      simple arm dominance. Analyses indicated that any cortical bone mass, area and
      thickness benefits of throwing-related physical activity completed when young
      were lost with aging, possibly due to accelerated intracortical remodeling. In
      contrast, the subject's throwing (nondominant) arm had greater total cross
      sectional area and estimated strength (polar moment of inertia) than in his
      dominant arm, despite muscle indices favoring the latter. These data indicate
      that physical activity completed when young can have lasting benefits on bone
      size and strength, independent of the maintenance of bone mass benefits. 

PMID- 24879029
TI  - Comment on: ''In vivo measurements of human bone deformation using optical
      segment tracking: surgical approach and validation in a three-point bending
      test''.

PMID- 24879030
TI  - Reply to the letter to the editor by Liu and Li.

PMID- 24879031
TI  - Does occupational noise cause asymmetric hearing loss?
AB  - OBJECTIVE: Determine whether occupational noise exposure increases audiometric
      asymmetry. DESIGN: Audiograms were performed on 2044 men from the Occupational
      Noise and Hearing Survey, representing four groups based on preliminary screening
      (for previous noise exposure, otologic history, and otoscopy) and current
      occupational noise exposure. The effects of current noise exposure on audiometric
      asymmetry were tested using ANCOVA, with binaural average thresholds as
      covariates. RESULTS: There were no significant differences in asymmetry
      attributable to current occupational noise exposure. RESULTS: Occupational noise
      exposure does not usually cause or exacerbate audiometric asymmetry.

PMID- 24879032
TI  - Massively parallel pyrosequencing of the mitochondrial genome with the 454
      methodology in forensic genetics.
AB  - RESULTS: of sequencing of whole mitochondrial genome, HV1 and HV2 DNA with the
      second generation system (SGS) Roche 454 GS Junior were compared with results of
      Sanger sequencing and SNP typing with SNaPshot single base extension detected
      with MALDI-TOF and capillary electrophoresis. We investigated the performance of
      the software analysis of the data, reproducibility, ability to sequence
      homopolymeric regions, detection of mixtures and heteroplasmy as well as the
      implications of the depth of coverage. We found full reproducibility between
      samples sequenced twice with SGS. We found close to full concordance between the
      mtDNA sequences of 26 samples obtained with (1) the 454 SGS method using a depth
      of coverage above 100 and (2) Sanger sequencing and SNP typing. The discrepancies
      were primarily observed in homopolymeric regions. The 454 SGS method was able to
      sequence 95% of the reads correctly in homopolymers up to 4 bases, and up to 6
      bases could be sequenced with similar success if the results were carefully,
      visually inspected. The 454 technology was able to detect mixtures or
      heteroplasmy of approximately 10%. We detected previously unreported heteroplasmy
      in the GM9947A component of the NIST human mitochondrial DNA SRM-2392 standard
      reference material.

PMID- 24879033
TI  - Three different histological subtypes of Epstein-Barr virus-negative post
      transplant lymphoproliferative disorder in a patient with hepatitis C infection.
AB  - We report a rare case in which Epstein-Barr virus (EBV)-negative polymorphic B
      cell post-transplant lymphoproliferative disorder (PTLD) and EBV-negative
      monomorphic T-cell PTLD [anaplastic lymphoma kinase (ALK)-positive anaplastic
      large cell lymphoma (ALCL)] were observed simultaneously in the same cervical
      lymph node, 34 months after liver transplantation for hepatitis C liver
      cirrhosis. Although hepatitis C recurred after 2 months, he had no other
      complications until PTLD occurred 34 months post-transplantation. The patient
      underwent reduction of the immunosuppressive drug and rituximab plus
      cyclophosphamide, doxorubicin, vincristine, and prednisone therapy, and he was
      considered to have achieved complete remission. However, PTLD recurred, and he
      died 6 months after the initial diagnosis. Autopsy revealed only EBV-negative
      monomorphic T-cell PTLD (ALK-negative ALCL) that involved the liver, spleen,
      bilateral kidneys, stomach, bladder, heart, bone marrow, right ureter, and pons.
      Thus, recurrent PTLD may show a different histological type from the primary
      disorder, as PTLD has a multiclonal potentiality that causes various types of
      lymphomas. Therefore, it may be difficult to predict PTLD-related prognosis from
      the initial PTLD histological identification. 

PMID- 24879034
TI  - Prognostic discrimination for early chronic phase chronic myeloid leukemia in
      imatinib era: comparison of Sokal, Euro, and EUTOS scores in Korean population.
AB  - Beyond the conventional Sokal and Euro scores, a new prognostic risk
      classification, based on the European Treatment Outcome Study (EUTOS), has been
      developed to predict the outcome of treatment with tyrosine kinase inhibitors
      (TKI) in chronic myeloid leukemia (CML). In the present study, each risk score
      was validated by various endpoints in 206 Korean patients with early chronic
      phase CML treated with up-front standard dose imatinib. In our analysis, all
      three scores were found to be valid. The 5-year event-free survival (EFS) was
      significantly discriminated using Sokal (P = 0.002), Euro (P = 0.003), and EUTOS
      (P = 0.029), with the worst probability by Euro high-risk (62 vs. 49 vs. 67 %)
      and better EFS in Sokal low-risk (89 vs. 86 vs. 82 %). Combining all scores
      identified 6 % of all patients having homogeneous high-risk with distinctively
      worse outcomes (5-year EFS of 41 %, cumulative complete cytogenetic response rate
      of 56 %, and cumulative major molecular response rate of 27 %), whereas the group
      of discordance in risk scores (60 %) had similar results to those of intermediate
      risk groups of Sokal and Euro scores. Combining all risk scores for baseline risk
      assessment may be useful in clinical practice for identifying groups of patients
      who may benefit from treatment initiation with a more potent TKI among the
      currently available first-line TKIs.

PMID- 24879035
TI  - Diagnosis of overt disseminated intravascular coagulation in critically Ill
      adults by Sonoclot coagulation analysis.
AB  - Disseminated intravascular coagulation (DIC) diagnosis is hampered by the limited
      availability of reliable clinical or laboratory tests. Currently available tests
      are time consuming and expensive. We investigated whether coagulation and
      platelet function analyses using the Sonoclot system were suitable for overt DIC
      diagnosis in critically ill adults. This was an observational diagnostic study
      performed in 498 patients presenting with an underlying disorder associated with
      DIC. Overt DIC patients were identified according to an International Society on
      Thrombosis and Hemostasis (ISTH) score of >5. Coagulation and platelet parameters
      were analyzed using the Sonoclot system, and compared with ISTH as the gold
      standard. Receiver operating characteristic curves and area under the curves were
      used to evaluate the value of the Sonoclot parameters. There were no differences
      for age or gender between the groups. Significant correlations were observed
      between activated clotting time (ACT) and ISTH score (r = 0.7; P < 0.001), clot
      rate (CR) and ISTH score (r = 0.5; P < 0.001), platelet function (PF) and ISTH
      score (r = -0.6; P < 0.001), and PF and platelet count (r = 0.5; P < 0.001). An
      ACT cut-off value of 213.5 s alone or combined with CR presented good sensitivity
      (76.7 and 86.8 %, respectively) and specificity (96.2 and 93.3 %, respectively).
      Sonoclot analysis can be performed using a point-of-care device that effectively
      discriminates low and high ISTH scores, and that effectively predicts coagulation
      dysfunction in patients with overt DIC.

PMID- 24879037
TI  - Review of the protective effects of rutin on the metabolic function as an
      important dietary flavonoid.
AB  - BACKGROUND: In recent years, flavonoids have been revealed to be helpful in the
      treatment of many diseases. Rutin (3,3',4',5,7-pentahydroxyflavone-3
      rhamnoglucoside) is an important flavonoid that is consumed in the daily diet. It
      is also known as vitamin P and quercetin-3-O-rutinoside. In addition, it is found
      in many food items, vegetables, and beverages. The cytoprotective effects of
      rutin, including gastroprotective, hepatoprotective, and anti-diabetic effects,
      have been shown in several studies. Furthermore, rutin has several
      pharmacological effects such as anti-inflammatory and anti-glycation activities.
      AIM: This work reviewed characteristic, pharmacokinetic, and metabolic effects of
      rutin in all experimental and human studies. CONCLUSIONS: Based on the above
      summarized effects of rutin, this flavonoid appears to be a potent component that
      could be considered in the treatment of several gastrointestinal diseases and
      diabetes.

PMID- 24879036
TI  - A polymorphism rs12325489C>T in the lincRNA-ENST00000515084 exon was found to
      modulate breast cancer risk via GWAS-based association analyses.
AB  - Breast cancer, one of the most common malignancies diagnosed among women
      worldwide, is a complex polygenic disease in the etiology of which genetic
      factors play an important role. Thus far, a subset of breast cancer genetic
      susceptibility loci has been addressed among Asian woman through genome-wide
      association studies (GWASs). In this study, we identified numerous long,
      intergenic, noncoding RNAs (lincRNAs) enriched in these breast cancer risk
      related loci and identified 16 single nucleotide polymorphisms (SNPs) located
      within the sequences of lincRNA exonic regions. We examined whether these 16 SNPs
      are associated with breast cancer risk in 2539 cancer patients and 2818 control
      subjects from eastern, southern, and northern Chinese populations. We found that
      the C allele of the rs12325489C>T polymorphism in the exonic regions of lincRNA
      ENST00000515084 was associated with a significantly increased risk of breast
      cancer (adjusted odds ratio [OR] = 1.79; 95% confidence interval [CI] = 1.50
      2.12), compared with the rs12325489TT genotype. Biochemical analysis demonstrated
      that the C to T base change at rs12325489C>T disrupts the binding site for miRNA
      370, thereby influencing the transcriptional activity of lincRNA-ENST00000515084
      in vitro and in vivo, and affecting cell proliferation and tumor growth. Our
      findings indicate that the rs12325489C>T polymorphism in the lincRNA
      ENST00000515084 exon may be a genetic modifier in the development of breast
      cancer. 

PMID- 24879038
TI  - Associations between attention, affect and cardiac activity in a single yoga
      session for female cancer survivors: an enactive neurophenomenology-based
      approach.
AB  - Yoga practice is reported to lead to improvements in quality of life,
      psychological functioning, and symptom indices in cancer survivors. Importantly,
      meditative states experienced within yoga practice are correlated to
      neurophysiological systems that moderate both focus of attention and affective
      valence. The current study used a mixed methods approach based in
      neurophenomenology to investigate associations between attention, affect, and
      cardiac activity during a single yoga session for female cancer survivors. Yoga
      practice was associated with a linear increase in associative attention and
      positive affective valence, while shifts in cardiac activity were related to the
      intensity of each yoga sequence. Changes in attention and affect were predicted
      by concurrently assessed cardiac activity. Awareness of breathing, physical
      movement, and increased relaxation were reported by participants as potential
      mechanisms for yoga's salutary effects. While yoga practice shares commonalities
      with exercise and relaxation training, yoga may serve primarily as a promising
      meditative attention-affect regulation training methodology. 

PMID- 24879039
TI  - Combined alloplastic implant and autologous dermis graft for nasal augmentation
      rhinoplasty in Asians.
AB  - Alloplastic implants may be used in augmentation rhinoplasty but are associated
      with thinning of the skin over the implant as well as extrusion and translucency
      of the implant. To minimize these complications, this report describes a combined
      alloplastic implant and autologous dermal graft for dorsal and tip augmentation
      rhinoplasty. Of 37 Chinese patients, 35 (94.6 %) were satisfied with the outcome
      of this procedure during a follow-up period of up to 24 months, and no implant
      extrusions occurred. The preliminary findings indicate that a combined
      alloplastic implant and autologous dermis graft is appropriate for nasal
      augmentation, especially for patients with thin tip skin. LEVEL OF EVIDENCE V:
      This journal requires that authors assign a level of evidence to each article.
      For a full description of these Evidence-Based Medicine ratings, please refer to
      the Table of Contents or the online Instructions to Authors
      www.springer.com/00266 .

PMID- 24879040
TI  - A rare complication of rhinoplasty: periorbital emphysema.
AB  - Subcutaneous emphysema is a clinical entity that may be associated with trauma.
      Rhinoplasty is not an atraumatic procedure. This report presents a case of acute
      periorbital emphysema after cosmetic rhinoplasty. LEVEL OF EVIDENCE V: This
      journal requires that authors assign a level of evidence to each article. For a
      full description of these Evidence-Based Medicine ratings, please refer to the
      Table of Contents or the online Instructions to Authors www.springer.com/00266 .

PMID- 24879041
TI  - What are the limits of the surgeon's responsibility in the operating theater?

PMID- 24879042
TI  - Informed consent in Italy-traditional versus the law: a gordian knot.
AB  - BACKGROUND: Italian law no. 86 of 5 June 2012, which establishes a set of rules
      on the matter of breast implants, came into effect in July 2012. The law is at
      the center of a widespread and animated cultural debate that in recent years has
      been taking place in Italy. DISCUSSION: The fundamental prohibition imposed by
      the law concerns the age limit. Breast implants for exclusively aesthetic
      purposes are allowed only if the legal age (18 years) has been reached. This
      prohibition does not apply in cases of severe congenital malformations certified
      by a physician operating within the National Health Service or by a public health
      care institution. The legal imposition of an age limit raises a number of
      perplexities: one at a bioethical level and one that is strictly juridical. In
      fact, it is impossible to deal with this issue unless the wider debate concerning
      the self-determination and autonomy of underage patients in biomedical matters is
      considered. It appears, then, that the issue is again exclusively related to the
      peculiarity of cosmetic surgery, which when aimed at correcting "only" the
      pathologic experiences of self-image, does not acquire the dignity of therapy.
      If, however, the improvement of self-image serves to achieve a better psycho
      emotional balance and favors the development of social relations undermined by
      evident physical defects, age restrictions can be disregarded. The authors
      believe the real risk is that the law imposed by the Italian state is based on
      assumptions and preformed value judgments. Furthermore, in the understanding of
      needs, legislation often is biased toward objective biophysical problems without
      attaching due importance to subjective psychological and social problems. While
      acknowledging the seriousness of the issue, the authors do not agree with the
      legislature's rigidity. However, plastic surgeons must form a plan for addressing
      the concerns about breast implants and evaluating whether they are appropriate
      for adolescents, taking into account the unique psychological and developmental
      considerations of adolescent cosmetic surgery patients. LEVEL OF EVIDENCE V: This
      journal requires that authors assign a level of evidence to each article. For a
      full description of these Evidence-Based Medicine ratings, please refer to the
      Table of Contents or the online Instructions to Authors www.springer.com/00266 .

PMID- 24879043
TI  - Different time trends by gender for the incidence of Hodgkin's lymphoma among
      young adults in the USA: a birth cohort phenomenon.
AB  - OBJECTIVES: Hodgkin's lymphoma (HL) is one of the most common cancers among young
      adults. We investigated the time trends for HL among the 20-44 age group in the
      USA by gender to identify the potential factors accounting for the incidence
      trends. METHODS: Using data from the National Cancer Institute's Surveillance,
      Epidemiology, and End Results program for 1973-2010, we conducted age-period
      cohort modeling to evaluate birth cohort patterns on incidence trends of HL over
      time. RESULTS: For all races combined, the age-adjusted incidence patterns were
      similar to that of whites. The birth cohort patterns for whites and all races
      were similar, but the patterns differed according to gender. Specifically, except
      for the 1970-1975 birth cohort, all other birth cohorts showed an increasing
      birth cohort trend for females. Conversely, there was a decreasing cohort trend
      in males beginning in the 1960 birth cohort regardless of the assumptions of the
      period effect. CONCLUSION: The established risk factors for HL can seemingly not
      explain the gender disparities of the cohort pattern, which necessitates further
      analytical epidemiological studies to explore the risk factors for this disease
      with respect to potential differences by gender and by histological subtype.

PMID- 24879044
TI  - The association between race and prostate cancer risk on initial biopsy in an
      equal access, multiethnic cohort.
AB  - PURPOSE: Population-based studies have established a link between race and
      prostate cancer (PC) risk, but whether race predicts PC after adjusting for
      clinical characteristics is unclear. We investigated the association between race
      and risk of low- and high-grade PC in men undergoing initial prostate biopsy in
      an equal access medical center. METHODS: We conducted a retrospective record
      review of 887 men (48.6 % black, 51.4 % white) from the Durham Veterans Affairs
      Medical Center who underwent initial prostate biopsy between 2001 and 2009.
      Multivariable logistic regression analysis of race and biopsy outcome was
      conducted adjusting for age, body mass index, number of cores taken, prostate
      specific antigen (PSA), and digital rectal examination findings. Multinomial
      logistic regression was used to test the association between black race and PC
      grade (Gleason <7 vs. >=7). RESULTS: Black men were younger at biopsy (61 vs. 65
      years, p < 0.001) and had a higher pre-biopsy PSA (6.6 vs. 5.8 ng/ml, p = 0.001).
      A total of 499 men had PC on biopsy (245 low grade; 254 high grade). In
      multivariable analyses, black race was significantly predictive of PC overall
      [odds ratio 1.50, p = 0.006] and high-grade PC [relative risk ratio (RRR) 1.84, p
      = 0.001], but was not significantly associated with low-grade PC (RRR 1.29, p =
      0.139). CONCLUSION: In an equal access healthcare facility, black race was
      associated with greater risk of PC detection on initial biopsy and of high-grade
      PC after adjusting for clinical characteristics. Additional investigation of
      mechanisms linking black race and PC risk and PC aggressiveness is needed.

PMID- 24879045
TI  - A combined ultrasound and histologic approach for analysis of uterine fibroid
      pseudocapsule thickness.
AB  - Authors investigated 75 patients with uterine myomas, appraising whether fibroid
      pseudocapsule (FP) thickness varies depending on fibroid location, by a
      prospective cohort trial (level of evidence II-2) settled in University
      affiliated Hospitals. Uteri were scanned via bidimensional and power Doppler
      ultrasound (US) to map the fibroids and record the FP thickness, prior to
      hysterectomy for symptomatic uterine fibroids. After hysterectomy, FP specimens
      were sampled and analyzed by pathologists. Ultrasound and histology data were
      matched. Pseudocapsule thickness of 108 fibroids was measured: subserosal
      fibroids (SSFs), intramural fibroids (IMFs), and fibroids near the endometrial
      cavity (FEC). The FEC's pseudocapsules were considerably thicker than those of
      IMF and SSF measured by US and histology (P = .001). A clear cutoff existed
      between FEC pseudocapsule thickness and all other pseudocapsules, with
      significant differences observed at 2 mm (P = .001). Similarity between
      histological and US measurements was observed only with IMF pseudocapsules,
      whereas FEC or SSF showed significant differences. The pseudocapsule of fibroids
      is considerably thicker near the endometrial cavity when compared to those of
      both IMFs and SSFs. Since fibroids closest to the endometrial cavity are the most
      involved in fertility and infertility and FP is considerably thicker near the
      endometrial cavity, it is possible to hypothesize an involvement of FP of fibroid
      near the endometrium since FP contains many neuropeptides and neurotransmitters
      that are physiologically active, even if these data may take on a broader meaning
      in a study on a larger number of patients. 

PMID- 24879046
TI  - Estradiol attenuates spinal cord injury-related central pain by decreasing
      glutamate levels in thalamic VPL nucleus in male rats.
AB  - Central neuropathic pain (CNP) is a complicated medical problem that involves
      both the spinal and supraspinal regions of the central nervous system. Estrogen,
      a neuroprotective agent, has been considered a possible candidate for CNP
      treatment. In this study, we examined the effects of a single dose of 17beta
      estradiol on glutamate levels in the ventral posterolateral (VPL) nucleus of the
      rat thalamus. Furthermore, we determined whether there was a correlation between
      glutamate levels and neuropathic pain induced by unilateral electrolytic
      spinothalamic tract (STT) lesion. STT lesioning was performed in male Wistar rats
      at the T8-T9 vertebrae; rats were then administered 17beta-estradiol (4 mg/kg,
      i.p.) 30 min after injury. Glutamate samples were collected using a microdialysis
      probe and quantified by high performance liquid chromatography. Mechanical
      allodynia (MA) and thermal hyperalgesia (TH) thresholds were measured pre-injury
      and 7, 14, and 28 days post-injury. We found that STT lesion significantly
      increased glutamate levels in the ipsilateral VPL nucleus 14 and 28 days post
      injury; this was accompanied by allodynia and hyperalgesia in the hind paws of
      the rats. Administering 17beta-estradiol to the rats decreased glutamate levels
      in the ipsilateral VPL nucleus and significantly increased MA and TH thresholds.
      These results suggest that glutamate in the VPL nucleus of the thalamus is
      involved in the pathology of neuropathic pain after STT injury; furthermore,
      17beta-estradiol may attenuate this neuropathic pain by decreasing glutamate
      levels.

PMID- 24879048
TI  - The effectiveness of the stabilization/solidification process on the leachability
      and toxicity of the tannery sludge chromium.
AB  - A stabilization/solidification (S/S) process by using cement was applied to
      tannery sludge in order to find a safer way of landfilling this waste. The
      effects of three parameters on the process effectiveness were analysed in terms
      of leachate toxicity and chromium retention (%). The parameters studied were the
      relative amount of added water (30-50 wt.%), cement (10-60 wt.% in the solid
      components), and the use of three different types of cement (clinker with
      additions of limestone, with additions of limestone and fly ashes, and with
      additions of pozzolans). Statistical analysis performed by variance analysis and
      categorical multifactorial tests reveals that all the studied parameters
      significantly influence the effectiveness of the process. Results showed that
      chromium retention decreases as the relative amount of cement and water
      increases, probably due to additional chromium provided by cement and increased
      in the porosity of the mixtures. Leachate toxicity showed the same minimum value
      for mixtures with 30% or 40% cement, depending on the type of cement, showing
      that clinker is the main material responsible for the process effectiveness, and
      additives (pozzolans or fly ashes) do not improve it. The volume increase is
      lower as less sludge is replaced by cement and the relative amount of water
      decreases, and for the cement without additions of fly ashes or pozzolans.
      Therefore, the latter seems to be the most appropriate cement in spite of being
      more expensive. This is due to the fact that the minimum toxicity value is
      achieved with a lower amount of cement; and moreover, the volume increase in the
      mixtures is lower, minimizing the disposal cost to a landfill. 

PMID- 24879047
TI  - Piperlongumine treatment inactivates peroxiredoxin 4, exacerbates endoplasmic
      reticulum stress, and preferentially kills high-grade glioma cells.
AB  - BACKGROUNDS: Piperlongumine, a natural plant product, kills multiple cancer types
      with little effect on normal cells. Piperlongumine raises intracellular levels of
      reactive oxygen species (ROS), a phenomenon that may underlie the cancer-cell
      killing. Although these findings suggest that piperlongumine could be useful for
      treating cancers, the mechanism by which the drug selectively kills cancer cells
      remains unknown. METHODS: We treated multiple high-grade glioma (HGG) sphere
      cultures with piperlongumine and assessed its effects on ROS and cell-growth
      levels as well as changes in downstream signaling. We also examined the levels of
      putative piperlongumine targets and their roles in HGG cell growth. RESULTS:
      Piperlongumine treatment increased ROS levels and preferentially killed HGG cells
      with little effect in normal brain cells. Piperlongumine reportedly increases ROS
      levels after interactions with several redox regulators. We found that HGG cells
      expressed higher levels of the putative piperlongumine targets than did normal
      neural stem cells (NSCs). Furthermore, piperlongumine treatment in HGG cells, but
      not in normal NSCs, increased oxidative inactivation of peroxiredoxin 4 (PRDX4),
      an ROS-reducing enzyme that is overexpressed in HGGs and facilitates proper
      protein folding in the endoplasmic reticulum (ER). Moreover, piperlongumine
      exacerbated intracellular ER stress, an effect that was mimicked by suppressing
      PRDX4 expression. CONCLUSIONS: Our results reveal that the mechanism by which
      piperlongumine preferentially kills HGG cells involves PRDX4 inactivation,
      thereby inducing ER stress. Therefore, piperlongumine treatment could be
      considered as a novel therapeutic option for HGG treatment.

PMID- 24879049
TI  - A coexistence case of right tubal adenomyoma and ectopic pregnancy.

PMID- 24879050
TI  - Quality of care and racial disparities in medicare among potential ACOs.
AB  - BACKGROUND: The Medicare Accountable Care Organization (ACO) programs encourage
      integration of providers into large groups and reward provider groups for
      improving quality, but not explicitly for reducing health care disparities.
      Larger group size and better overall quality may or may not be associated with
      smaller disparities. OBJECTIVE: To examine differences in patient characteristics
      between provider groups sufficiently large to participate in ACO programs and
      smaller groups; the association between group size and racial disparities in
      quality; and the association between quality and disparities among larger groups.
      DESIGN AND PARTICIPANTS: Using 2009 Medicare claims for 3.1 million beneficiaries
      with cardiovascular disease or diabetes and linked data on provider groups, we
      compared racial differences in quality by provider group size, adjusting for
      patient characteristics. Among larger groups, we used multilevel models to
      estimate correlations between group performance on quality measures for white
      beneficiaries and black-white disparities within groups. MAIN MEASURES: Four
      process measures of quality, hospitalization for ambulatory care-sensitive
      conditions (ACSCs) related to cardiovascular disease or diabetes, and
      hospitalization for any ACSC. KEY RESULTS: Beneficiaries served by larger groups
      were more likely to be white and live in areas with less poverty and more
      education. Larger group size was associated with smaller disparities in low
      density lipoprotein (LDL) cholesterol testing and retinal exams, but not in other
      process measures or hospitalization for ACSCs. Among larger groups, better
      quality for white beneficiaries in one measure (hospitalization for ACSCs related
      to cardiovascular disease or diabetes) was correlated with smaller racial
      disparities (r = 0.28; P = 0.02), but quality was not correlated with disparities
      in other measures. CONCLUSIONS: Larger provider group size and better performance
      on quality measures were not consistently associated with smaller racial
      disparities in care for Medicare beneficiaries with cardiovascular disease or
      diabetes. ACO incentives rewarding better quality for minority groups and payment
      arrangements supporting ACO development in disadvantaged communities may be
      required for ACOs to promote greater equity in care.

PMID- 24879053
TI  - Galen and the beginnings of Western physiology.
AB  - Galen (129-c. 216 AD) was a key figure in the early development of Western
      physiology. His teachings incorporated much of the ancient Greek traditions
      including the work of Hippocrates and Aristotle. Galen himself was a well
      educated Greco-Roman physician and physiologist who at one time was a physician
      to the gladiators in Pergamon. Later he moved to Rome, where he was associated
      with the Roman emperors Marcus Aurelius and Lucius Verus. The Galenical school
      was responsible for voluminous writings, many of which are still extant. One
      emphasis was on the humors of the body, which were believed to be important in
      disease. Another was the cardiopulmonary system, including the belief that part
      of the blood from the right ventricle could enter the left through the
      interventricular septum. An extraordinary feature of these teachings is that they
      dominated thinking for some 1,300 years and became accepted as dogma by both the
      State and Church. One of the first anatomists to challenge the Galenical
      teachings was Andreas Vesalius, who produced a magnificent atlas of human anatomy
      in 1543. At about the same time Michael Servetus described the pulmonary transit
      of blood, but he was burned at the stake for heresy. Finally, with William Harvey
      and others in the first part of the 17th century, the beginnings of modern
      physiology emerged with an emphasis on hypotheses and experimental data.
      Nevertheless, vestiges of Galen's teaching survived into the 19th century. 

PMID- 24879051
TI  - gamma-Herpes virus-68, but not Pseudomonas aeruginosa or influenza A (H1N1),
      exacerbates established murine lung fibrosis.
AB  - Patients with idiopathic pulmonary fibrosis (IPF) often do worse following
      infection, but the cause of the decline is not fully understood. We previously
      demonstrated that infection with a murine gamma herpes virus (gammaHV-68) could
      exacerbate established lung fibrosis following administration of fluorescein
      isothiocyanate (McMillan et al. Am J Respir Crit Care Med 177: 771-780, 2008). In
      the present study, we anesthetized mice and injected saline or bleomycin
      intratracheally on day 0. On day 14, mice were anesthetized again and infected
      with either a Gram-negative bacteria (Pseudomonas aeruginosa), or with H1N1 or
      gammaHV-68 viruses. Measurements were then made on days 15, 21, or 35. We
      demonstrate that infection with P. aeruginosa does not exacerbate extracellular
      matrix deposition post-bleomycin. Furthermore, fibrotic mice are effectively able
      to clear P. aeruginosa infection. In contrast, bleomycin-treated mice develop
      worse lung fibrosis when infected with gammaHV-68, but not when infected with
      H1N1. The differential ability of gammaHV-68 to cause increased collagen
      deposition could not be explained by differences in inflammatory cell recruitment
      or whole lung chemokine and cytokine responses. Alveolar epithelial cells from
      gammaHV-68-infected mice displayed increased expression of TGFbeta receptor 1,
      increased SMAD3 phosphorylation, and evidence of apoptosis measured by cleaved
      poly-ADP ribose polymerase (PARP). The ability of gammaHV-68 to augment fibrosis
      required the ability of the virus to reactivate from latency. This property
      appears unique to gammaHV-68, as the beta-herpes virus, cytomegalovirus, did not
      have the same effect. 

PMID- 24879054
TI  - Interrelated role of cigarette smoking, oxidative stress, and immune response in
      COPD and corresponding treatments.
AB  - Cigarette smoking (CS) can impact the immune system and induce pulmonary
      disorders such as chronic obstructive pulmonary disease (COPD), which is
      currently the fourth leading cause of chronic morbidity and mortality worldwide.
      Accordingly, the most significant risk factor associated with COPD is exposure to
      cigarette smoke. The purpose of the present study is to provide an updated
      overview of the literature regarding the effect of CS on the immune system and
      lungs, the mechanism of CS-induced COPD and oxidative stress, as well as the
      available and potential treatment options for CS-induced COPD. An extensive
      literature search was conducted on the PubMed/Medline databases to review current
      COPD treatment research, available in the English language, dating from 1976 to
      2014. Studies have investigated the mechanism by which CS elicits detrimental
      effects on the immune system and pulmonary function through the use of human and
      animal subjects. A strong relationship among continued tobacco use, oxidative
      stress, and exacerbation of COPD symptoms is frequently observed in COPD
      subjects. In addition, therapeutic approaches emphasizing smoking cessation have
      been developed, incorporating counseling and nicotine replacement therapy.
      However, the inability to reverse COPD progression establishes the need for
      improved preventative and therapeutic strategies, such as a combination of
      intensive smoking cessation treatment and pharmaceutical therapy, focusing on
      immune homeostasis and redox balance. CS initiates a complex interplay between
      oxidative stress and the immune response in COPD. Therefore, multiple approaches
      such as smoking cessation, counseling, and pharmaceutical therapies targeting
      inflammation and oxidative stress are recommended for COPD treatment. 

PMID- 24879052
TI  - Arginase II is a target of miR-17-5p and regulates miR-17-5p expression in human
      pulmonary artery smooth muscle cells.
AB  - Vascular remodeling and smooth muscle cell proliferation are hallmark pathogenic
      features of pulmonary artery hypertension. MicroRNAs, endogenously expressed
      small noncoding RNAs, regulate gene expression at the posttranscriptional level.
      It has previously been shown that miR-17 overexpression in cultured human
      pulmonary artery smooth muscle cell (hPASMC) resulted in increased viable cell
      number. Previously, we have found that arginase II promotes hypoxia-induced
      proliferation in hPASMC. Therefore, we hypothesized that miR-17 would be
      upregulated by hypoxia in hPASMC and would result in greater arginase II
      expression. We found that levels of miR-17-5p and arginase II were significantly
      greater in cultured hPASMC exposed to 1% O2 for 48 h than in hPASMC exposed to
      21% O2 for 48 h. Furthermore, inhibiting miR-17-5p expression decreased hypoxia
      induced arginase II protein levels in hPASMC. Conversely, overexpressing miR-17
      5p resulted in greater arginase II protein levels. Somewhat surprisingly,
      arginase II inhibition was associated with lower miR-17-5p expression in both
      normoxic and hypoxic hPASMC, whereas overexpressing arginase II resulted in
      greater miR-17-5p expression in hPASMC. These findings suggest that hypoxia
      induced arginase II expression is not only regulated by miR-17-5p but also that
      there is a feedback loop between arginase II and miR-17-5p in hPASMC. We also
      found that the arginase II-mediated regulation of miR-17-5p was independent of
      either p53 or c-myc. We also found that l-arginine, the substrate for arginase
      II, and l-ornithine, the amino acid product of arginase II, were not involved in
      the regulation of miR-17-5p expression. 

PMID- 24879055
TI  - Airway collagen and elastic fiber content correlates with lung function in equine
      heaves.
AB  - The consequences on lung function and inflammation of alterations in the
      extracellular matrix affecting the peripheral airway wall in asthma are largely
      unknown. We hypothesized that remodeling of collagen and elastic fibers in the
      peripheral airway wall leads to airway obstruction and contributes to
      neutrophilic airway inflammation. Animals used were six heaves-affected horses
      and five controls. Large peripheral lung biopsies were obtained from horses with
      heaves in clinical remission (Baseline) and during disease exacerbation and from
      age-matched controls. The area of collagen and elastic fiber content in the
      lamina propria was measured by histological staining techniques and corrected for
      airway size. Collagen type 1 and type 3 content was further assessed from
      additional horses after postmortem lung samples by immunohistochemistry. The
      collagen breakdown products proline-glycine-proline (PGP) and N-acetylated-PGP (N
      alpha-PGP) were also measured in bronchoalveolar lavage fluids (BALF) by mass
      spectrometry. Compared with controls, heaves-affected horses had an increase in
      collagen (P = 0.05) and elastic fiber contents (P = 0.04) at baseline. Collagen
      types 1 and 3 content was also significantly increased in diseased horses (P =
      0.015) when both collagen types were combined. No further change in collagen
      content was observed after a 30-day antigenic challenge. Airway collagen at
      baseline was positively correlated with pulmonary resistance in asthmatic horses
      (r(2) = 0.78, P = 0.03) and elastic fiber content was positively associated with
      pulmonary elastance in controls (r(2) = 0.95, P = 0.02). No difference between
      groups was appreciated in PGP and N-alpha-PGP peptides in BALF. Increased airway
      wall collagen and elastic fiber content may contribute to residual obstruction in
      the asthmatic airways. 

PMID- 24879057
TI  - Orbital Varix Thrombosis and Review of Orbital Vascular Anomalies in Blue Rubber
      Bleb Nevus Syndrome.
AB  - A 57-year-old woman with cutaneous manifestations of (BRBNS) presented with acute
      left proptosis and venous congestion secondary to thrombosis within a superior
      ophthalmic vein varix. Multiple phleboliths were noted in the contralateral right
      orbit, and an incidental right middle cerebral artery aneurysm. Her symptoms
      spontaneously resolved within a few days. An English literature review found 7
      reported cases of orbital vascular lesions in association with BRBNS from 1950 to
      2012. All lesions showed contrast enhancement on CT or MRI: 4 had small orbital
      calcifications and 3 were distensible with raised venous pressure. The occurrence
      of a thrombosed orbital varix or cerebral artery aneurysm in BRBNS, to the best
      of the authors' knowledge, has not been previously reported. Although orbital
      vascular lesions in BRBNS have been described as hemangiomas, the biologic
      behavior and histology of most of the reported orbital lesions are most
      compatible with venous malformations. 

PMID- 24879056
TI  - Chloride channel blockade relaxes airway smooth muscle and potentiates relaxation
      by beta-agonists.
AB  - Severe bronchospasm refractory to beta-agonists continues to cause significant
      morbidity and mortality in asthmatic patients. We questioned whether chloride
      channels/transporters are novel targets for the relaxation of airway smooth
      muscle (ASM). We have screened a library of compounds, derivatives of anthranilic
      and indanyloxyacetic acid, that were originally developed to antagonize chloride
      channels in the kidney. We hypothesized that members of this library would be
      novel calcium-activated chloride channel blockers for the airway. The initial
      screen of this compound library identified 4 of 20 compounds that relaxed a
      tetraethylammonium chloride-induced contraction in guinea pig tracheal rings. The
      two most effective compounds, compounds 1 and 13, were further studied for their
      potential to either prevent the initiation of or relax the maintenance phase of
      an acetylcholine (ACh)-induced contraction or to potentiate beta-agonist-mediated
      relaxation. Both relaxed an established ACh-induced contraction in human and
      guinea pig ex vivo ASM. In contrast, the prevention of an ACh-induced contraction
      required copretreatment with the sodium-potassium-chloride cotransporter blocker
      bumetanide. The combination of compound 13 and bumetanide also potentiated
      relaxation by the beta-agonist isoproterenol in guinea pig tracheal rings.
      Compounds 1 and 13 hyperpolarized the plasma cell membrane of human ASM cells and
      blocked spontaneous transient inward currents, a measure of chloride currents in
      these cells. These functional and electrophysiological data suggest that
      modulating ASM chloride flux is a novel therapeutic target in asthma and other
      bronchoconstrictive diseases. 

PMID- 24879058
TI  - Effects of phylogeny, leaf traits, and the altitudinal distribution of host
      plants on herbivore assemblages on congeneric Acer species.
AB  - Historical, niche-based, and stochastic processes have been proposed as the
      mechanisms that drive community assembly. In plant-herbivore systems, these
      processes can correspond to phylogeny, leaf traits, and the distribution of host
      plants, respectively. Although patterns of herbivore assemblages among plant
      species have been repeatedly examined, the effects of these factors among co
      occurring congeneric host plant species have rarely been studied. Our aim was to
      reveal the process of community assembly for herbivores by investigating the
      effects of phylogeny, leaf traits, and the altitudinal distribution of closely
      related host plants of the genus Acer. We sampled leaf functional traits for 30
      Acer species in Japan. Using a newly constructed phylogeny, we determined that
      three of the six measured leaf traits (leaf thickness, C/N ratio, and condensed
      tannin content) showed a phylogenetic signal. In a field study, we sampled
      herbivore communities on 14 Acer species within an elevation gradient and
      examined relationships between herbivore assemblages and host plants. We found
      that herbivore assemblages were significantly correlated with phylogeny, leaf
      traits, phylogenetic signals, and the altitudinal distribution of host plants.
      Our results indicate that the interaction between historical and current
      ecological processes shapes herbivore community assemblages. 

PMID- 24879060
TI  - Autonomic Reactivity to Infant Crying in Maltreating Mothers.
AB  - We examined autonomic reactivity to infant crying in a sample of 42 maltreating
      and 38 non-maltreating mothers. Exploratively, we tested if differential
      reactivity was related to child neglect versus the combination of neglect and
      abuse, and we tested whether mothers' experiences with maltreatment in their own
      childhood moderated the association between their current maltreatment status and
      physiology. During a standardized cry paradigm, mothers listened to cry sounds of
      various pitches. Heart rate (HR), pre-ejection period (PEP), skin conductance
      levels (SCLs), and vagal tone (root mean square of successive differences
      [RMSSD]) were measured as indicators of underlying sympathetic and
      parasympathetic reactivity. The maltreating mothers showed lower SCL reactivity
      to the cry sounds than non-maltreating mothers. Furthermore, significant negative
      correlations between HR and PEP in the non-maltreating group differed from
      nonsignificant correlations in the maltreating group, which suggests a lack of
      sympathetic cardiac control in maltreating mothers. We found no differences
      between neglectful mothers and those who were additionally abusive. Together, our
      findings support the notion of sympathetic hypoarousal as a risk factor for child
      maltreatment, which may be indicative of disengagement in a caregiving context.
      Intervention programs might focus on improving maternal sensitivity to improve
      responsiveness to child signals.

PMID- 24879059
TI  - Alternatively spliced tissue factor is not sufficient for embryonic development.
AB  - Tissue factor (TF) triggers blood coagulation and is translated from two mRNA
      splice isoforms, encoding membrane-anchored full-length TF (flTF) and soluble
      alternatively-spliced TF (asTF). The complete knockout of TF in mice causes
      embryonic lethality associated with failure of the yolk sac vasculature. Although
      asTF plays roles in postnatal angiogenesis, it is unknown whether it activates
      coagulation sufficiently or makes previously unrecognized contributions to
      sustaining integrity of embryonic yolk sac vessels. Using gene knock-in into the
      mouse TF locus, homozygous asTF knock-in (asTFKI) mice, which express murine asTF
      in the absence of flTF, exhibited embryonic lethality between day 9.5 and 10.5.
      Day 9.5 homozygous asTFKI embryos expressed asTF protein, but no procoagulant
      activity was detectable in a plasma clotting assay. Although the alpha-smooth
      muscle-actin positive mesodermal layer as well as blood islands developed
      similarly in day 8.5 wild-type or homozygous asTFKI embryos, erythrocytes were
      progressively lost from disintegrating yolk sac vessels of asTFKI embryos by day
      10.5. These data show that in the absence of flTF, asTF expressed during
      embryonic development has no measurable procoagulant activity, does not support
      embryonic vessel stability by non-coagulant mechanisms, and fails to maintain a
      functional vasculature and embryonic survival. 

PMID- 24879061
TI  - Neuroproteome changes after ischemia/reperfusion injury and tissue plasminogen
      activator administration in rats: a quantitative iTRAQ proteomics study.
AB  - The thrombolytic, recombinant tissue plasminogen activator (rt-PA) is the only
      approved therapy for acute ischemic stroke (AIS). When administered after AIS, rt
      PA has many adverse pleiotropic actions, which are currently poorly understood.
      The identification of proteins showing differential expression after rt-PA
      administration may provide insight into these pleiotropic actions. In this study
      we used a 2D-LC MS/MS iTRAQ proteomic analysis, western blotting, and pathway
      analysis to analyze changes in protein expression 24-hours after rt-PA
      administration in the cortical brain tissue of 36 rats that underwent a sham or
      transient middle cerebral artery occlusion surgery. After rt-PA administration we
      reported alterations in the expressions of 18 proteins, many of which were
      involved in excitatory neurotransmitter function or cytoskeletal structure. The
      expression changes of GAD2 and EAAT1 were validated with western blot. The
      interactions between the identified proteins were analyzed with the IPA pathway
      analysis tool and three proteins: DPYSL2, RTN4, and the NF-kB complex, were found
      to have characteristics of being key proteins in the network. The differential
      protein expressions we observed may reflect pleiotropic actions of rt-PA after
      experimental stroke, and shine light on the mechanisms of rt-PA's adverse
      effects. This may have important implications in clinical settings where
      thrombolytic therapy is used to treat AIS. 

PMID- 24879063
TI  - The accuracy of pre-appendectomy computed tomography with histopathological
      correlation: a clinical audit, case discussion and evaluation of the literature.
AB  - The increasing use of computed tomography (CT) in acute appendicitis makes
      recognising the radiological hallmarks of the condition and its mimics vital. The
      differential diagnosis includes both appendiceal and nonappendiceal pathologies.
      The correlation between pre-appendectomy CT and post-appendectomy histopathology
      was audited retrospectively. Cases of clinico-histopathological discrepancy
      underwent blind peer-review, and possible improvements were discussed in the
      context of the medical literature. A grade for discrepancy was given based on the
      RADPEER scoring system, and interesting or discrepant cases were examined more
      closely to identify targets for education. Of the 199 procedures, 4
      appendectomies were negative (histologically normal), 182 were positive (primary
      appendicitis) and 13 were incidental (another primary process caused
      inflammation). The positive predictive value for pre-appendectomy CT was 91.5 %,
      and the negative appendectomy rate was 2 %. There were many secondary
      pathologies, including neoplasia, tuberculosis and endometriosis. Although no CT
      reports missed a diagnosis that should be made "almost all of the time" and in 96
      % of cases, the second, blinded radiologist agreed with the initial assessment,
      in 3 cases, a missed diagnosis altered clinical management; 2 were
      "understandable" misses but 1 was not. In five cases, a discrepancy was
      "understandable" but clinically insignificant. Overall, in comparison to the
      medical literature, the degree of clinico-histopathological correlation was good.
      Although identifying areas for improvement was challenging, after a pictorial
      review of four cases and a discussion of the medical literature, we present our
      audit results and some valuable learning points for use in the CT assessment of
      suspected acute appendicitis. 

PMID- 24879064
TI  - Identification and multiplicity of double vowels in cochlear implant users.
AB  - PURPOSE: The present study examined cochlear implant (CI) users' perception of
      vowels presented concurrently (i.e., double vowels) to further our understanding
      of auditory grouping in electric hearing. METHOD: Identification of double vowels
      and single vowels was measured with 10 CI subjects. Fundamental frequencies (F0s)
      of vowels were either 100 + 100 Hz or 100 + 300 Hz. Vowels were presented either
      synchronously or with a time delay. In "Double" sessions, subjects were given
      only double vowels. In "Double + Single" sessions, while double and single vowels
      were presented, subjects reported the number and identity of the vowel(s). In
      addition to clinical settings, stimuli were delivered via an experimental method
      that interleaved pulse streams of two vowels. RESULTS: Although the time delay
      between vowels had a large effect on identification, the effect of change in
      fundamental frequency (DeltaF0) was modest. Enumeration was poor in general, and
      identification of synchronous vowels was above chance in only the Double sessions
      with a priori knowledge about presentation. Interleaved presentation of vowel
      streams provided no benefit for identification and a marginal benefit for
      enumeration. CONCLUSIONS: The results demonstrate the importance of episodic
      context for CI users. Unreliable perception of multiplicity observed in the
      present results suggests that auditory grouping in CIs may be driven by a schema
      based process.

PMID- 24879065
TI  - Restoration of lost frequency in OpenPET imaging: comparison between the method
      of convex projections and the maximum likelihood expectation maximization method.
AB  - We are developing a new PET scanner based on the "OpenPET" geometry, which
      consists of two detector rings separated by a gap. One item to which attention
      must be paid is that OpenPET image reconstruction is classified into an
      incomplete inverse problem, where low-frequency components are truncated. In our
      previous simulations and experiments, however, the OpenPET imaging was made
      feasible by application of iterative image reconstruction methods. Therefore, we
      expect that iterative methods have a restorative effect to compensate for the
      lost frequency. There are two types of reconstruction methods for improving image
      quality when data truncation exists: one is the iterative methods such as the
      maximum-likelihood expectation maximization (ML-EM) and the other is an
      analytical image reconstruction method followed by the method of convex
      projections, which has not been employed for the OpenPET. In this study,
      therefore, we propose a method for applying the latter approach to the OpenPET
      image reconstruction and compare it with the ML-EM. We found that the proposed
      analytical method could reduce the occurrence of image artifacts caused by the
      lost frequency. A similar tendency for this restoration effect was observed in ML
      EM image reconstruction where no additional restoration method was applied.
      Therefore, we concluded that the method of convex projections and the ML-EM had a
      similar restoration effect to compensate for the lost frequency.

PMID- 24879062
TI  - A comparative study of the effects of inhibitory cytokines on human natural
      killer cells and the mechanistic features of transforming growth factor-beta.
AB  - The major factors and mechanisms by which natural killer (NK) cells are inhibited
      in cancer patients have not yet been well defined. In this study, we conducted a
      comparative analysis of the effects of TGF-beta, IL-10, and IL-4 on primary NK
      cells, and it was demonstrated that (1) TGF-beta most potently inhibited the
      overall function of NK cells. (2) It appears that TGF-beta reduced the tyrosine
      phosphorylation of Syk and the expression of c-myc. (3) It was also found that
      the IL-2-induced promoter-binding activities of C-myb, AP-1, CREB, and AR were
      also completely suppressed upon TGF-beta treatment. Interestingly, TGF-beta also
      completely suppressed other transcription factors, which are constitutively
      activated. Among these factors, we further confirmed roles of AP-1 in NK-92 cell
      activation through c-jun and MEK1 inhibitor assay. Our study provides insight
      into the effects of TGF-beta in modulating NK cell functions.

PMID- 24879067
TI  - Differential sensitivity of Glioma stem cells to Aurora kinase A inhibitors:
      implications for stem cell mitosis and centrosome dynamics.
AB  - Glioma stem-cell-like cells are considered to be responsible for treatment
      resistance and tumour recurrence following chemo-radiation in glioblastoma
      patients, but specific targets by which to kill the cancer stem cell population
      remain elusive. A characteristic feature of stem cells is their ability to
      undergo both symmetric and asymmetric cell divisions. In this study we have
      analysed specific features of glioma stem cell mitosis. We found that glioma stem
      cells appear to be highly prone to undergo aberrant cell division and
      polyploidization. Moreover, we discovered a pronounced change in the dynamic of
      mitotic centrosome maturation in these cells. Accordingly, glioma stem cell
      survival appeared to be strongly dependent on Aurora A activity. Unlike
      differentiated cells, glioma stem cells responded to moderate Aurora A inhibition
      with spindle defects, polyploidization and a dramatic increase in cellular
      senescence, and were selectively sensitive to Aurora A and Plk1 inhibitor
      treatment. Our study proposes inhibition of centrosomal kinases as a novel
      strategy to selectively target glioma stem cells. 

PMID- 24879066
TI  - SJL mice infected with Acanthamoeba castellanii develop central nervous system
      autoimmunity through the generation of cross-reactive T cells for myelin
      antigens.
AB  - We recently reported that Acanthamoeba castellanii (ACA), an opportunistic
      pathogen of the central nervous system (CNS) possesses mimicry epitopes for
      proteolipid protein (PLP) 139-151 and myelin basic protein 89-101, and that the
      epitopes induce experimental autoimmune encephalomyelitis (EAE) in SJL mice
      reminiscent of the diseases induced with their corresponding cognate peptides. We
      now demonstrate that mice infected with ACA also show the generation of cross
      reactive T cells, predominantly for PLP 139-151, as evaluated by T cell
      proliferation and IAs/dextramer staining. We verified that PLP 139-151-sensitized
      lymphocytes generated in infected mice contained a high proportion of T helper 1
      cytokine-producing cells, and they can transfer disease to naive animals.
      Likewise, the animals first primed with suboptimal dose of PLP 139-151 and later
      infected with ACA, developed EAE, suggesting that ACA infection can trigger CNS
      autoimmunity in the presence of preexisting repertoire of autoreactive T cells.
      Taken together, the data provide novel insights into the pathogenesis of
      Acanthamoeba infections, and the potential role of infectious agents with mimicry
      epitopes to self-antigens in the pathogenesis of CNS diseases such as multiple
      sclerosis. 

PMID- 24879069
TI  - Continuous irrigation as a therapeutic option for graft infections of the groin.
AB  - BACKGROUND: Wound infections following vascular procedures occur in 1-7 % of
      patients and can lead to severe problems including amputation and death. There
      are no established treatment options for this complication. The aim of our study
      was to introduce continuous irrigation as a new treatment technique. METHODS: We
      retrospectively evaluated patients who had undergone bypass surgery involving the
      groin and had been treated with continuous irrigation because of deep wound
      infections. The irrigation solution was saline in all cases. The patients were
      additionally treated with antibiotics. The end point of the study was either
      complete wound healing or complications such as recurrent infection, amputation,
      or death. RESULTS: Wound complications occurred in 65 (15.3 %) of 424 operations.
      Overall, 20 patients (4.7 %) developed a deep wound infection involving
      prosthetic graft material. They were treated with continuous irrigation. Complete
      wound healing was achieved in 13 cases (65.0 %). One patient died. No amputations
      were necessary. CONCLUSIONS: Based on our results, constant irrigation may be a
      therapeutic option in patients with deep wound infections. The main advantages of
      continuous irrigation over other treatments are ongoing bacterial reduction
      despite primary wound closure and the ability to measure the remaining
      colonization by microbiologic examination of the irrigation fluid.

PMID- 24879068
TI  - Fumarylacetoacetate hydrolase deficient pigs are a novel large animal model of
      metabolic liver disease.
AB  - Hereditary tyrosinemia type I (HT1) is caused by deficiency in
      fumarylacetoacetate hydrolase (FAH), an enzyme that catalyzes the last step of
      tyrosine metabolism. The most severe form of the disease presents acutely during
      infancy, and is characterized by severe liver involvement, most commonly
      resulting in death if untreated. Generation of FAH(+/-) pigs was previously
      accomplished by adeno-associated virus-mediated gene knockout in fibroblasts and
      somatic cell nuclear transfer. Subsequently, these animals were outbred and
      crossed to produce the first FAH(-/-) pigs. FAH-deficiency produced a lethal
      defect in utero that was corrected by administration of 2-(2-nitro-4
      trifluoromethylbenzoyl)-1,3 cyclohexanedione (NTBC) throughout pregnancy. Animals
      on NTBC were phenotypically normal at birth; however, the animals were euthanized
      approximately four weeks after withdrawal of NTBC due to clinical decline and
      physical examination findings of severe liver injury and encephalopathy
      consistent with acute liver failure. Biochemical and histological analyses,
      characterized by diffuse and severe hepatocellular damage, confirmed the
      diagnosis of severe liver injury. FAH(-/-) pigs provide the first genetically
      engineered large animal model of a metabolic liver disorder. Future applications
      of FAH(-/-) pigs include discovery research as a large animal model of HT1 and
      spontaneous acute liver failure, and preclinical testing of the efficacy of liver
      cell therapies, including transplantation of hepatocytes, liver stem cells, and
      pluripotent stem cell-derived hepatocytes. 

PMID- 24879070
TI  - The impact of combined pulmonary fibrosis and chronic obstructive pulmonary
      disease on long-term survival after lung cancer surgery.
AB  - PURPOSE: The purpose of this study was to determine the impact of pulmonary
      fibrosis (PF) on postoperative complications and on long-term survival after
      surgical resection in lung cancer patients with chronic obstructive pulmonary
      disease (COPD). PATIENTS AND METHODS: A retrospective chart review was conducted
      of 380 patients with COPD who had undergone pulmonary resection for lung cancer
      at the University Hospital between 1990 and 2005. The definition of COPD was a
      preoperative forced expiratory volume in 1 second/forced vital capacity
      (FEV1/FVC) ratio of less than 70%; PF was defined as obvious bilateral fibrous
      change in the lower lung fields, confirmed by computed tomography. RESULTS: PF
      was present in 41 patients (10.8%) with COPD; the remaining 339 patients (89.2%)
      did not have PF. The preoperative FVC/FEV1 was significantly lower in the group
      of patients with PF than in the group without (p < 0.05). Acute lung injury and
      home oxygen therapy were significantly more common in the PF group; however, the
      30-day mortality was similar between the groups. The cumulative survival at 3 and
      5 years was 53.6 and 36.9%, respectively, in the PF group and 71.4 and 66.1%,
      respectively, in the non-PF group (p = 0.0009). Increased age, decreased body
      mass index, advanced pathologic stage, and the existence of PF were identified as
      independent risk factors for decreased survival. CONCLUSION: PF is a risk factor
      for decreased survival after surgical treatment in lung cancer patients with
      COPD.

PMID- 24879071
TI  - Chiari malformation unmasked by accidental dural puncture.

PMID- 24879072
TI  - Septic arthritis of both knees following intra-articular injection of petrol.
AB  - A 70 years old man was referred to our center with bilateral knee arthritis
      following intra-articular petrol injection. Because of previous antibiotics use
      gram stain and culture were negative. Septic arthritis was diagnosed and
      antibiotics and drainage were started. After 2 years he improved eventually and
      was able to walk. But, some movement limitation remained.

PMID- 24879073
TI  - The PARTY program: a systematic approach to injury prevention for young road
      users around the world.

PMID- 24879074
TI  - Mumblety-Peg: a potential cause of flesh wounds and ocular trauma.

PMID- 24879075
TI  - The effects of injections of warmed bicarbonate-buffered Lidocaine as a
      painkiller for patients with trauma.

PMID- 24879076
TI  - Prevalence and attributes of criminality in patients with schizophrenia.
AB  - BACKGROUND: Existing research in law and psychiatry point to schizophrenia as a
      risk factor for violence and offense behaviors. The present study aims to: 1)
      report on the prevalence and types of offensive or criminal acts in patients with
      schizophrenia; 2) identify attributes of schizophrenic offenders; and 3) examine
      factors associated with offensive or criminal behaviors within a sample of
      schizophrenic offenders. METHODS: This was a cross-sectional study of 358
      patients with schizophrenia who were admitted to a psychiatric ward in Iran
      between 2004 and 2008. Study data was collected using patients' medical, criminal
      records, as well as via personal interview with the family member. Study
      variables included criminality or offensive behavior, types of schizophrenia
      (paranoid vs. nonparanoid), experiencing hallucination, disease onset, and
      patients' demographics. RESULTS: Of the sample, 64.8% were male, 80.7% were 45
      years old or younger, and 74.1% were either single or divorced. Slightly over 59
      % were offenders with criminal status, of which, 9.8% were legal offenders and
      48.6% were hidden offenders. The results of unadjusted logistic regression
      between these variables and criminality show, except for employment, marital
      status, and opium use, all other variables were statically associated with
      criminality. CONCLUSIONS: Methodological difficulties arising from this study, as
      well as, the role of mental health professionals, family, and legal system for
      prevention of violence in and by patients with schizophrenia are discussed.

PMID- 24879077
TI  - School-based violence prevention strategy: a pilot evaluation.
AB  - BACKGROUND: Violence has recently been reported among a primarily young, minority
      population in Nashville, Tennessee. School-based programs have been proven as
      effective methods of reducing violent behavior, beliefs, and actions that lead to
      violence among adolescents. METHODS: Investigators implemented a rigorous search
      for an appropriate school-based violence prevention program for Metropolitan
      Nashville middle school students utilizing a systematic review and discussion
      group with victims of violence. 27 programs nation-wide were reviewed and 2
      discussion groups with African American males under the age of 25 admitted to a
      level 1 trauma center for assault-related injuries were conducted. Our findings
      led to a single, evidence-based conflict resolution program. In conjunction with
      educators, we evaluated the program's effectiveness in a pilot study in a
      Nashville middle school with high rates of violence. RESULTS: 122 students
      completed the conflict resolution program and described their behavior and
      experiences with violence in a pre-test/post-test self-rate questionnaire.
      Results showed a significant decrease in violent behavior and an increase in
      students' competencies to deal with violence (p less than 0.05). CONCLUSIONS:
      This study shows that a reduction in violent behavior and beliefs among middle
      school students can be achieved through the implementation of a targeted violence
      intervention program. A larger-scale intervention is needed to develop more
      conclusive evidence of effectiveness.

PMID- 24879078
TI  - Why should being visible on the road? A challenge to prevent road traffic
      injuries among pedestrians in Iran.

PMID- 24879079
TI  - Exploring possible causes of fatal burns in 2007 using Haddon's Matrix: a
      qualitative study.
AB  - BACKGROUND: Burns are a major factor in injury mortality. The aim of this study
      was to explore the possible causes of fatal burns using Haddon's Matrix. METHODS:
      This is a qualitative study using a phenomenological approach. We collected
      elicitation interview data using nine corroborators who were the most
      knowledgeable about the index burn event. Immediately after recording, the data
      was verbatim. Each event was analyzed using Haddon's Matrix. RESULTS:
      Interviewees provided detailed information about 11 burn cases. Overall, 202 burn
      related factors were extracted. Using Haddon's Matrix, 43 risk factors were
      identified. The most common included the lack of basic knowledge of burn care,
      the use of unsafe appliances including kerosene heaters and stoves in hazardous
      environments such kitchens and bathrooms, poor burn care delivery system in
      hospitals, poor and unsafe living conditions, financial issues, and other factors
      detailed in the article. CONCLUSIONS: Our findings suggest burn related
      prevention efforts should focus on improving human living conditions, promoting
      the use of safe heating appliances, providing public burn-safety precautions
      education, and improving the quality of care in burn centers and hospitals. The
      use of Haddon's Matrix in future injury research is discussed.

PMID- 24879080
TI  - Utility of combining assessment of right ventricular function and right atrial
      remodeling as a prognostic factor for patients with pulmonary hypertension.
AB  - We tested the hypothesis that the addition of right atrial (RA) remodeling to
      right ventricular (RV) function enhances the capability of the latter to predict
      long-term outcome for pulmonary hypertension (PH) patients. We studied 82 PH
      patients, all of whom underwent echocardiography and right heart catheterization.
      RV function was calculated by averaging the three regional peak speckle-tracking
      longitudinal strains from RV free wall (RV-free). RA remodeling was assessed as
      the RA area traced planimetrically at end-systole. Pre-defined cutoffs for RV
      dysfunction and RA remodeling were RV-free <=19.4 % and RA area of >18 cm(2),
      respectively. Long-term unfavorable outcome events were tracked for 2.0 years. RA
      area correlated with mean RA pressure (r = 0.62, p < 0.001), as well as with
      tricuspid E/E' (r = 0.38, p = 0.001). Moreover, RA area in patients with RV
      restrictive filling was significantly larger than that in patients with others
      (all p < 0.05). Kaplan-Meier analysis revealed that patients with RV-free <=19.4
      % had worse long-term outcomes than those with RV-free >19.4 % (log-rank p =
      0.01), as did patients with RA area >18 cm(2) compared with those with RA area
      <=18 cm(2) (log-rank p < 0.05). For sequential Cox models, a model based on
      hemodynamic parameters of RV performance (chi2 = 3.11) was improved by addition
      of brain natriuretic peptide, World Health Organization functional class (chi2 =
      9.24; p < 0.05), and RV-free (chi2 = 17.11; p = 0.005), and further improved by
      addition of RA area (chi2 = 21.36, p < 0.05). In conclusion, the combined
      assessment of RV function and RA area results in more accurate prediction of long
      term outcome, and may well have clinical implications for better management of PH
      patients.

PMID- 24879082
TI  - Pregnancy in women with primary biliary cirrhosis.
AB  - BACKGROUND & AIMS: Primary biliary cirrhosis (PBC) may present in all decades of
      life, also in childbearing age. Data on maternal and fetal outcome is limited. We
      aimed to investigate the impact of pregnancy and childbirth on the disease course
      and possible effects of PBC on fetal outcome. METHODS: Retrospective study of
      local cases and a compact review of published reports between 1950 and 2014.
      RESULTS: Our cases along with literature review provided 98 pregnancies in 72 PBC
      patients. PBC was diagnosed during pregnancy in 26 (36%) patients and 46 (64%)
      had the diagnosis before conception. Twenty-four (30%) of the pregnancies were
      associated with biochemical flares and 55 (70%) with clinical improvement or
      stabilization. De novo onset or worsening of pruritus was seen in 49% (45/92). No
      maternal deaths were reported. Post-partum disease activation was observed in 60%
      (53/88). One patient was referred for liver transplantation after delivery. A
      miscarriage rate of 24% and three stillbirths were reported. Most patients were
      treated with ursodeoxycholic acid (UDCA) during breastfeeding and 12 patients
      also received UDCA during the first trimester without any identified side
      effects. CONCLUSION: Most women with PBC maintain a stable disease during
      pregnancy, but post-partum biochemical flares are common. Symptomatic pruritus
      may be challenging in pregnant PBC patients. UDCA appears to be safe during
      pregnancy and breastfeeding. A successful pregnancy outcome is a realistic
      expectation for women with PBC.

PMID- 24879081
TI  - Repeated sense of hunger leads to the development of visceral obesity and
      metabolic syndrome in a mouse model.
AB  - Obesity-related disorders, especially metabolic syndrome, contribute to 2.8
      million deaths each year worldwide, with significantly increasing morbidity.
      Eating at regular times and proper food quantity are crucial for maintaining a
      healthy status. However, many people in developed countries do not follow a
      regular eating schedule due to a busy lifestyle. Herein, we show that a repeated
      sense of hunger leads to a high risk of developing visceral obesity and metabolic
      syndrome in a mouse model (both 3-week and 6-week-old age, 10 mice in each
      group). The ad libitum (AL) group (normal eating pattern) and the food
      restriction (FR) group (alternate-day partially food restriction by given only
      1/3 of average amount) were compared after 8-week experimental period. The total
      food consumption in the FR group was lower than in the AL group, however, the FR
      group showed a metabolic syndrome-like condition with significant fat
      accumulation in adipose tissues. Consequently, the repeated sense of hunger
      induced the typical characteristics of metabolic syndrome in an animal model; a
      distinct visceral obesity, hyperlipidemia, hyperglycemia and hepatic steatosis.
      Furthermore, we found that specifically leptin, a major metabolic hormone, played
      a major role in the development of these pathological disorders. Our study
      indicated the importance of regular eating habits besides controlling calorie
      intake. 

PMID- 24879083
TI  - Relative mRNA expression and immunolocalization for transforming growth factor
      beta (TGF-beta) and their effect on in vitro development of caprine preantral
      follicles.
AB  - This study aimed to evaluate the immunolocalization and messenger RNA (mRNA)
      expression for transforming growth factor-beta (TGF-beta) and its receptors (TGF
      betaRI and RII), as well as mRNA expression for P450 aromatase and FSH receptor
      in caprine preantral follicles. The effects of TGF-beta, FSH alone, or in
      association on the in vitro follicular development were also assessed.
      Immunohistochemical analyses showed the expression of TGF-beta and its receptors
      in oocytes of all follicle stages and granulosa cells of primary and secondary
      follicles. mRNA for TGF-beta receptors and for FSH receptor (FSHR) was present in
      preantral follicles as well as in oocytes and granulosa cells of antral
      follicles. Isolated secondary follicles were cultured in alpha-minimum essential
      medium (MEM) alone or supplemented with either FSH (100 ng/ml), TGF-beta (10
      ng/ml), or TGF-beta + FSH for 18 d. TGF-beta increased significantly oocyte
      diameter when compared to FSH alone and control. After 18 d of culture, all
      groups showed a significant reduction in P450 aromatase and FSHR mRNA levels in
      comparison to fresh control. In contrast, treatment with FSH significantly
      increased the mRNA expression for TGF-beta in comparison to fresh control and
      other treatments. In conclusion, the findings showed that TGF-beta and its
      receptors are present in caprine ovarian follicles. Furthermore, they showed a
      positive effect on oocyte growth in vitro. 

PMID- 24879086
TI  - Effects of age-related macular degeneration and ambient light on curb
      negotiation.
AB  - PURPOSE: To determine how age-related macular degeneration (AMD) and changes in
      ambient light affect the ability to negotiate a curb while walking. METHODS: Ten
      older adults with AMD and 11 normal-sighted control subjects performed a curb
      negotiation task under normal light (~600 lux), dim light (~0.7 lux), and
      following a sudden reduction (~600 to 0.7 lux) of light. In this task, subjects
      walked and stepped up or down a simulated sidewalk curb. Movement kinematics and
      ground reaction forces were measured during curb ascent and descent. Habitual
      visual acuity, contrast sensitivity, and visual fields were also assessed.
      RESULTS: Apart from slower gait speed in those with AMD, there were no
      differences between groups during curb ascent for any other measure. During curb
      descent, older adults with AMD frequently used shuffling steps in the approach
      phase to locate the curb edge and showed prolonged double support duration
      stepping over the curb compared with control subjects. However, reduced lighting,
      particularly a sudden reduction, led to several significant changes in movement
      characteristics in both groups. For instance, toe clearance stepping up the curb
      was greater, and landing force stepping down was reduced. In addition, slower
      gait speed and greater double support duration were evident in curb ascent and
      descent. In AMD subjects, contrast sensitivity, visual acuity, and visual field
      threshold were associated with several kinematic measures in the three light
      conditions during curb negotiation. CONCLUSIONS: Minor AMD-specific changes in
      movement are seen during curb negotiation. However, attenuated lighting greatly
      impacts curb ascent and descent, regardless of eye disease, which manifests as a
      cautious walking strategy and may increase the risk of falling. Environmental
      enhancements that reduce the deleterious effects of poor lighting are required to
      improve mobility and quality of life of older adults, particularly those with
      AMD.

PMID- 24879084
TI  - In vitro development of porcine transgenic nuclear-transferred embryos derived
      from newborn Guangxi Bama mini-pig kidney fibroblasts.
AB  - Porcine transgenic cloning has potential applications for improving production
      traits and for biomedical research purposes. To produce a transgenic clone,
      kidney fibroblasts from a newborn Guangxi Bama mini-pig were isolated, cultured,
      and then transfected with red and green fluorescent protein genes using
      lipofectamine for nuclear transfer. The results of the present study show that
      the kidney fibroblasts exhibited excellent proliferative capacity and clone-like
      morphology, and were adequate for generation of somatic cell nuclear transfer
      (SCNT)-derived embryos, which was confirmed by their cleavage activity and
      blastocyst formation rate of 70.3% and 7.9%, respectively. Cells transfected with
      red fluorescent protein genes could be passed more than 35 times. Transgenic
      embryos cloned with fluorescent or blind enucleation methods were not
      significantly different with respect to cleavage rates (92.5% vs. 86.8%, p >
      0.05) and blastocyst-morula rates (26.9% vs. 34.0%, p > 0.05), but were
      significantly different with respect to blastocyst rates (3.0% vs. 13.2%, p <
      0.05). Cleavage (75.3%, 78.5% vs. 78.0%, p > 0.05), blastocyst (14.1%, 16.1% vs.
      23.1%, p > 0.05) and morula/blastocyst rates (43.5%, 47.0% vs. 57.6%, p > 0.05)
      were not significantly different between the groups of transgenic cloned embryos,
      cloned embryos, and parthenogenetic embryos. This indicates that long-time
      screening by G418 caused no significant damage to kidney fibroblasts. Thus,
      kidney fibroblasts represent a promising new source for transgenic SCNT, and this
      work lays the foundation for the production of genetically transformed cloned
      Guangxi Bama mini-pigs.

PMID- 24879085
TI  - Is renal function associated with early age-related macular degeneration?
AB  - PURPOSE: Age-related macular degeneration (AMD) and chronic kidney disease both
      involve immune dysregulation and may share underlying pathophysiologic changes to
      systemic homeostasis. Hence, we aim to evaluate associations between impaired
      kidney function and early AMD, in a search for urinary biomarkers for AMD.
      METHODS: A population-based, cross-sectional analysis of persons aged 45 to 84
      years was conducted with renal function measured using serum creatinine and
      cystatin C levels and the estimated glomerular filtration rate (eGFR) calculated.
      Age-related macular degeneration status was ascertained from retinal photographs.
      RESULTS: Of 5874 participants, 221 had early AMD. High serum cystatin C and low
      eGFR (<=60 ml/min/1.73 m) were not associated with early AMD in our multivariate
      analyses. Among normotensive persons, however, highest versus other deciles of
      cystatin C were associated with an increased prevalence of early AMD (odds ratio,
      1.80; 95% confidence interval, 1.00 to 3.23). CONCLUSIONS: Results could not
      confirm an association between kidney function and early AMD. The borderline
      association between cystatin C and early AMD in normotensive persons require
      further verification.

PMID- 24879087
TI  - Melanopsin-expressing intrinsically photosensitive retinal ganglion cells in
      retinal disease.
AB  - Melanopsin-containing intrinsically photosensitive retinal ganglion cells
      (ipRGCs) are a class of photoreceptors with established roles in non-image
      forming processes. Their contributions to image-forming vision may include the
      estimation of brightness. Animal models have been central for understanding the
      physiological mechanisms of ipRGC function and there is evidence of conservation
      of function across species. Intrinsically photosensitive retinal ganglion cells
      can be divided into five ganglion cell subtypes that show morphological and
      functional diversity. Research in humans has established that ipRGCs signal
      environmental irradiance to entrain the central body clock to the solar day for
      regulating circadian processes and sleep. In addition, ipRGCs mediate the pupil
      light reflex (PLR), making the PLR a readily accessible behavioral marker of
      ipRGC activity. Less is known about ipRGC function in retinal and optic nerve
      disease, with emerging research providing insight into their function in
      diabetes, retinitis pigmentosa, glaucoma, and hereditary optic neuropathy. We
      briefly review the anatomical distributions, projections, and basic physiological
      mechanisms of ipRGCs and their proposed and known functions in animals and humans
      with and without eye disease. We introduce a paradigm for differentiating inner
      and outer retinal inputs to the pupillary control pathway in retinal disease and
      apply this paradigm to patients with age-related macular degeneration (AMD). In
      these cases of patients with AMD, we provide the initial evidence that ipRGC
      function is altered and that the dysfunction is more pronounced in advanced
      disease. Our perspective is that with refined pupillometry paradigms, the PLR can
      be extended to AMD assessment as a tool for the measurement of inner and outer
      retinal dysfunction.

PMID- 24879088
TI  - Trends in age-related macular degeneration management in Singapore.
AB  - PURPOSE: To describe the trends and patterns of anti-vascular endothelial growth
      factor (anti-VEGF) therapy and photodynamic therapy (PDT) use for age-related
      macular degeneration (AMD) in the National Eye Centre in Singapore over a 4-year
      period. METHODS: Data on the total number of intravitreal anti-VEGF injections
      and PDT treatment over a 4-year period at the Singapore National Eye Centre were
      obtained from centralized electronic records. Patients aged 40 years and older
      treated for AMD were included. Data retrieved included the annual treatment load
      in terms of number of new patients and total treatment episodes, and treatment
      burden for patients was studied in terms of number of injections per year and
      cumulative injection numbers over 3 years. Potential influence on retreatment by
      choice of drug, use of adjunct PDT, and diagnosis of polypoidal choroidal
      vasculopathy were further analyzed. RESULTS: From 2009 to 2012, a total of 6157
      injections were performed on 1380 unique individual patients. The total number of
      injections performed per calendar year increased from 962 in 2009 to 2278 in
      2012. The number of unique incident cases increased from 287 in 2009 to 446 in
      2012. The mean number of injections over the first year increased from 2.62 in
      2009 to 3.19 in 2012 (p < 0.001). Choice of anti-VEGF therapy did not
      significantly alter the cumulative injections required. Patients diagnosed as
      having polypoidal choroidal vasculopathy had similar injection episodes (p =
      0.178), whereas choice of anti-VEGF and adjunct PDT had no effect on the overall
      treatment. CONCLUSIONS: Anti-VEGF treatment of AMD continues to increase
      substantially year on year in the past few years, in alignment with experience
      from other countries. However, the cumulative number of injections per patient
      remains low, and many patients discontinue treatment within the first year. These
      data demonstrate that undertreatment remains a significant concern in clinical
      settings.

PMID- 24879089
TI  - Age-related macular degeneration: linking clinical presentation to pathology.
AB  - Age-related macular degeneration (AMD) is one of the leading causes of blindness
      worldwide in the elderly population. Optometrists, as primary eye health care
      providers, require the skills and knowledge to accurately diagnose and manage AMD
      patients. There is an overwhelming body of research related to the clinical
      presentation, etiology, epidemiology, and pathology of this disease.
      Additionally, the evolution of new imaging modalities creates new opportunities
      to clinically detect and analyze previously uncharacterized and earlier changes
      in the retina. The challenge for optometrists is to combine all this information
      into an applicable knowledge base for use in everyday clinical assessment of AMD
      so that timely and accurate referrals can be made to retinal specialists. This
      review attempts to address this issue by linking the clinical presentation of AMD
      with the underlying disease biology. We emphasize the contribution of recent
      noninvasive imaging technologies to the clinical assessment of early and more
      advanced AMD including optical coherence tomography, fundus autofluorescence, and
      infrared reflectance.

PMID- 24879090
TI  - Effect of visible light on catalytic hydrolysis of p-nitrophenyl palmitate by the
      Pseudomonas cepacia lipase immobilized on sol-gel support.
AB  - This paper demonstrates Pseudomonas cepacia lipase catalyzed hydrolysis of p
      nitrophenyl palmitate under irradiation of light with wavelengths of 250-750 nm.
      The reaction follows Michaelis-Menten Kinetics and the light irradiation
      increases the overall rate of hydrolysis. Using Lineweaver-Burk plot K M and V
      max values for the reaction in presence of light are found to be 39.07 and 66.67
      mM/min/g, respectively; while for the same reaction under dark condition, the
      values are 7.08 and 10.21 mM/min/g. The linear form of enzyme dependent rate of
      reaction confirms that no mass-transfer limitations are present and the reaction
      is a kinetically controlled enzymatic reaction. 

PMID- 24879092
TI  - Assessing Sexual Interest in Adolescents Who Have Sexually Offended.
AB  - Adolescents who have sexually offended have unique treatment needs. For mental
      health professionals to adequately address these unique needs, further research
      is necessary. To that end, we explored the assessment of sexual interest (which
      may play an integral role in understanding potential for sexual reoffending) in a
      sample of 103 male adolescents who have sexually offended. We compared results
      from a physiological assessment (MONARCH 21 penile plethysmography [PPG]) and an
      actuarial assessment (Screening Scale for Pedophilic Interest [SSPI]), plus data
      from an unobstrusive assessment (Affinity, a viewing time measure) in a smaller
      subsample of 16 male adolescents. One finding that has particular relevance for
      clinical assessment is that the SSPI may have limited utility with adolescents.
      We also found evidence for some overlap between data from PPG and viewing time
      assessments, although whether or not PPG data are ipsatized may affect
      relationships with other assessment modalities.

PMID- 24879091
TI  - MicroRNA-target gene responses to lead-induced stress in cotton (Gossypium
      hirsutum L.).
AB  - MicroRNAs (miRNAs) play key roles in plant responses to various metal stresses.
      To investigate the miRNA-mediated plant response to heavy metals, cotton
      (Gossypium hirsutum L.), the most important fiber crop in the world, was exposed
      to different concentrations (0, 25, 50, 100, and 200 uM) of lead (Pb) and then
      the toxicological effects were investigated. The expression patterns of 16 stress
      responsive miRNAs and 10 target genes were monitored in cotton leaves and roots
      by quantitative real-time PCR (qRT-PCR); of these selected genes, several miRNAs
      and their target genes are involved in root development. The results show a
      reciprocal regulation of cotton response to lead stress by miRNAs. The
      characterization of the miRNAs and the associated target genes in response to
      lead exposure would help in defining the potential roles of miRNAs in plant
      adaptation to heavy metal stress and further understanding miRNA regulation in
      response to abiotic stress. 

PMID- 24879094
TI  - Genetic risk load according to the site of intracranial aneurysms.
AB  - OBJECTIVE: We investigated whether risk alleles of single nucleotide
      polymorphisms associated with intracranial aneurysm (IA) are enriched in patients
      with familial IA, IA located at the middle cerebral artery (MCA), or IA rupture
      at a younger age. METHODS: In this case-only study, we calculated genetic risk
      scores (GRS) for 973 Dutch and 718 Finnish patients with IA by summing effect
      size-weighted risk allele counts of 7 single nucleotide polymorphisms associated
      with IAs previously identified through genome-wide association studies. We tested
      the GRS for association with presence of familial IA or IA at the MCA using
      logistic regression, and with age at time of IA rupture using linear regression.
      We also calculated odds ratios with 95% confidence intervals for the proportion
      of patients with each characteristic in the highest compared with the lowest GRS
      tertile. RESULTS: GRS were higher in IA at the MCA in the Dutch (p = 2.5 * 10(
      4)), Finnish (p = 0.039), and combined cohort (p = 4.9 * 10(-5)). GRS were not
      associated with familial IA in the Dutch (p = 0.34), Finnish (p = 0.45), and
      combined cohort (p = 0.98), or with age at time of IA rupture in the Dutch (p =
      0.28), Finnish (p = 0.86), and combined cohort (p = 0.45). In the combined
      cohort, odds ratios were 0.89 (0.67-1.20) for familial IA, 1.03 (0.79-1.34) for
      lower age, and 1.54 (1.20-1.98) for MCA aneurysms. CONCLUSIONS: Our findings
      suggest that genetic risk factors have a larger role in the development of IA at
      the MCA than at other sites, and that genetic heterogeneity should be considered
      in future genetic studies.

PMID- 24879095
TI  - Invasive fungal infections after obinutuzumab monotherapy for refractory chronic
      lymphocytic leukemia.

PMID- 24879093
TI  - Candida zeylanoides as a new yeast model for lipid metabolism studies: effect of
      nitrogen sources on fatty acid accumulation.
AB  - Lipid homeostasis is well-known in oleaginous yeasts, but there are few non
      oleaginous yeast models apart from Saccharomyces cerevisiae. We are proposing the
      non-oleaginous yeast Candida zeylanoides QU 33 as model. The aim of this study
      was to investigate the influence of the carbon/nitrogen ratio and the type of
      nitrogen source upon oil accumulation by this yeast grown on shake flask
      cultures. The maximum biomass was obtained in yeast extract (2.39 +/- 0.19 g/l),
      followed by peptone (2.24 +/- 0.05 g/l), while the highest content of microbial
      oil (0.35 +/- 0.01 g/l) and the maximum lipid yield (15.63%) were achieved with
      peptone. Oleic acid was the predominant cellular fatty acid in all culture media
      (>32.23%), followed by linoleic (>15.79%) and palmitic acids (>13.47%). The
      highest lipid yield using glucose and peptone was obtained at the C/N ratio of
      200:1.

PMID- 24879096
TI  - Effect of diethylcarbamazine citrate and Setaria equina excretory-secretory
      material on rat hepatocellular carcinoma.
AB  - Diethylcarbamazine citrate (DEC) has been known for its efficacy to eradicate
      bancroftian filariasis in Egypt and other countries in the world. One of the
      known effects was to decrease the level of circulating filarial antigen in the
      patient's serum. The target of this study was to examine the effect of DEC,
      excretory-secretory (ES) material from the filarial parasite Setaria equina or a
      combination of both on the status of oxidative stress and pathogenesis of rat
      hepatocellular carcinoma (HCC) induced by diethylnitrosamine and 2
      acetylaminofluorene. This could be tested in vitro using nitroblue tetrazolium
      reduction test for measuring the level of superoxide anion (O2(*-)) released from
      rat peritoneal macrophages. For in vivo test, a single dose before induction of
      carcinogenesis or continually repeated doses with DEC, ES or DEC + ES was used.
      Exposure of macrophages to ES could lead to a significant decrease (p < 0.01) in
      O2(*-) release, while DEC (200 MUM) could modulate such effect with significant
      increase (p < 0.05). Pathogenesis of liver cancer and treatment were evaluated
      using histological investigation, level of antioxidant and liver function
      enzymes. Repeated ES doses could increase the activity of antioxidant enzymes,
      especially the catalase enzyme and show a protective effect on liver
      architecture. DEC could modulate the later effects when combined with ES. No
      significant effect on the liver function enzymes after treatment was observed.
      Nuclear factor kappaB was found to be localized only in the cytoplasm after
      single and repeated treatments with ES. This study could indicate the effect of
      S. equina ES as antioxidant against rat HCC, while DEC could modulate such effect
      when combined with it.

PMID- 24879097
TI  - Heterogeneity in the differentiation and function of CD8+ T cells.
AB  - It is well established that CD8(+) T cells constitute an important branch of
      adaptive immunity contributing to clearance of intracellular pathogens and
      providing long-term protection. These functions are mostly fulfilled by the best
      characterized subpopulation of CD8(+) T cells, the cytotoxic T lymphocytes (also
      called Tc1 cells), owing to their ability to kill infected cells and to secrete
      cytokines such as interferon-gamma and tumor necrosis factor-alpha. However,
      there is growing evidence for alternative CD8(+) T cell fates influencing CD4(+)
      T-cell-mediated responses in the context of allergy, autoimmunity and infections.
      Thus, like subpopulations of CD4(+) T cells, also CD8(+) T cells under particular
      conditions acquire the expression of interleukin (IL)-4, IL-5, IL-9, IL-13, IL-17
      or suppressive activity and thereby influence immune responses. The process of
      CD8(+) T-cell differentiation is dictated by antigen strength, co-stimulatory
      molecules and cytokines. These environmental cues induce transcription factors
      further specifying CD8(+) T-cell decision into Tc1, Tc2, Tc9, Tc17 or CD8(+) T
      regulatory fate. Here, we discuss our current understanding about functional
      diversity of effector CD8(+) T cells and contribution of transcription factors to
      this process. 

PMID- 24879099
TI  - Update on congenital nasolacrimal duct obstruction.

PMID- 24879100
TI  - Use of telemedicine in retinopathy of prematurity.

PMID- 24879098
TI  - Skin-derived mesenchymal stem cells help restore function to ovaries in a
      premature ovarian failure mouse model.
AB  - Skin-derived mesenchymal stem cells (SMSCs) can differentiate into the three
      embryonic germ layers. For this reason, they are considered a powerful tool for
      therapeutic cloning and offer new possibilities for tissue therapy. Recent
      studies showed that skin-derived stem cells can differentiate into cells
      expressing germ-cell specific markers in vitro and form oocytes in vivo. The idea
      that SMSCs may be suitable for the treatment of intractable diseases or traumatic
      tissue damage has attracted attention. To determine the ability of SMSCs to
      reactivate injured ovaries, a mouse model with ovaries damaged by busulfan and
      cyclophosphamide was developed and is described here. Female skin-derived
      mesenchymal stem cells (F-SMSCs) and male skin-derived mesenchymal stem cells (M
      SMSCs) from red fluorescence protein (RFP) transgenic adult mice were used to
      investigate the restorative effects of SMSCs on ovarian function. Significant
      increases in total body weight and the weight of reproductive organs were
      observed in the treated animals. Both F-SMSCs and M-SMSCs were shown to be
      capable of partially restoring fertility in chemotherapy-treated females.
      Immunostaining with RFP and anti-Mullerian hormone (AMH) antibodies demonstrated
      that the grafted SMSCs survived, migrated to the recipient ovaries. After SMSCs
      were administered to the treated mice, real-time PCR showed that the expression
      levels of pro-inflammatory cytokines TNF-alpha, TGF-beta, IL-8, IL-6, IL-1beta,
      and IFNgamma were significantly lower in the ovaries than in the untreated
      controls. Consistent with this observation, expression of oogenesis marker genes
      Nobox, Nanos3, and Lhx8 increased in ovaries of SMSCs-treated mice. These
      findings suggest that SMSCs may play a role within the ovarian follicle
      microenvironment in restoring the function of damaged ovaries and could be useful
      in reproductive health. 

PMID- 24879101
TI  - Update on divergence insufficiency.

PMID- 24879102
TI  - Amblyopia: current evidence-based therapeutic options.

PMID- 24879103
TI  - Pediatric vision screening.

PMID- 24879104
TI  - Blepharoptosis in childhood.

PMID- 24879105
TI  - Periorbital and orbital infantile hemangiomas.

PMID- 24879106
TI  - Orthoptic management of incomitant strabismus.

PMID- 24879107
TI  - Monocular elevator deficiency.

PMID- 24879108
TI  - Anterior segment dysgenesis.

PMID- 24879109
TI  - Ocular manifestations of phakomatoses.

PMID- 24879111
TI  - Preface.

PMID- 24879112
TI  - Methods and considerations for longitudinal structural brain imaging analysis
      across development.
AB  - Magnetic resonance imaging (MRI) has allowed the unprecedented capability to
      measure the human brain in vivo. This technique has paved the way for
      longitudinal studies exploring brain changes across the entire life span. Results
      from these studies have given us a glimpse into the remarkably extended and
      multifaceted development of our brain, converging with evidence from anatomical
      and histological studies. Ever-evolving techniques and analytical methods provide
      new avenues to explore and questions to consider, requiring researchers to
      balance excitement with caution. This review addresses what MRI studies of
      structural brain development in children and adolescents typically measure and
      how. We focus on measurements of brain morphometry (e.g., volume, cortical
      thickness, surface area, folding patterns), as well as measurements derived from
      diffusion tensor imaging (DTI). By integrating finding from multiple longitudinal
      investigations, we give an update on current knowledge of structural brain
      development and how it relates to other aspects of biological development and
      possible underlying physiological mechanisms. Further, we review and discuss
      current strategies in image processing, analysis techniques and modeling of brain
      development. We hope this review will aid current and future longitudinal
      investigations of brain development, as well as evoke a discussion amongst
      researchers regarding best practices. 

PMID- 24879113
TI  - Developmental changes in the reward positivity: an electrophysiological
      trajectory of reward processing.
AB  - Children and adolescents learn to regulate their behavior by utilizing feedback
      from the environment but exactly how this ability develops remains unclear. To
      investigate this question, we recorded the event-related brain potential (ERP)
      from children (8-13 years), adolescents (14-17 years) and young adults (18-23
      years) while they navigated a "virtual maze" in pursuit of monetary rewards. The
      amplitude of the reward positivity, an ERP component elicited by feedback
      stimuli, was evaluated for each age group. A current theory suggests the reward
      positivity is produced by the impact of reinforcement learning signals carried by
      the midbrain dopamine system on anterior cingulate cortex, which utilizes the
      signals to learn and execute extended behaviors. We found that the three groups
      produced a reward positivity of comparable size despite relatively longer ERP
      component latencies for the children, suggesting that the reward processing
      system reaches maturity early in development. We propose that early development
      of the midbrain dopamine system facilitates the development of extended goal
      directed behaviors in anterior cingulate cortex. 

PMID- 24879114
TI  - Impact of gene dosage on gene expression, biological processes and survival in
      cervical cancer: a genome-wide follow-up study.
AB  - We investigated the role of tumor copy number (CN)-altered genome (CN-AG) in the
      carcinogenesis of cervical cancer (CC), especially its effect on gene expression,
      biological processes, and patient survival. Fifty-nine human papillomavirus 16
      (HPV16)-positive CCs were investigated with microarrays-31 for mapping CN-AG and
      55 for global gene expression, with 27 CCs in common. Five-year survival was
      investigated in 55 patients. Deletions and amplifications >2.5 Mb were defined as
      CN alterations. The %CN-AG varied from 0 to 32.2% (mean = 8.1+/-8.9). Tumors were
      classified as low (mean = 0.5+/-0.6, n = 11), medium (mean = 5.4+/-2.4, n = 10),
      or high (mean = 19.2+/-6.6, n = 10) CN. The highest %CN-AG was found in 3q, which
      contributed an average of 55% of all CN alterations. Genome-wide, only 5.3% of CN
      altered genes were deregulated directly by gene dosage. In contrast, the rate in
      fully duplicated 3q was twice as high. Amplification of 3q explained 23.2% of
      deregulated genes in whole tumors (r2 = 0.232, p = 0.006; analysis of variance),
      including genes located in 3q and other chromosomes. A total of 862 genes were
      deregulated exclusively in high-CN tumors, but only 22.9% were CN altered. This
      suggests that the remaining genes are not deregulated directly by gene dosage,
      but by mechanisms induced in trans by CN-altered genes. Anaphase-promoting
      complex/cyclosome (APC/C)-dependent proteasome proteolysis, glycolysis, and
      apoptosis were upregulated, whereas cell adhesion and angiogenesis were
      downregulated exclusively in high-CN tumors. The high %CN-AG and upregulated gene
      expression profile of APC/C-dependent proteasome proteolysis were associated with
      poor patient survival (p<0.05, log-rank test). Along with glycolysis, they were
      linearly associated with FIGO stage (r>0.38, p<0.01, Spearman test). Therefore,
      inhibition of APC/C-dependent proteasome proteolysis and glycolysis could be
      useful for CC treatment. However, whether they are indispensable for tumor growth
      remains to be demonstrated. 

PMID- 24879115
TI  - The role of front-line anthracycline-containing chemotherapy regimens in
      peripheral T-cell lymphomas.
AB  - Peripheral T-cell lymphomas (PTCLs) are a heterogenous group of aggressive non
      Hodgkin's lymphomas that are incurable in the majority of patients with current
      therapies. Outcomes associated with anthracycline-based therapies are suboptimal,
      but remain the standard of care for most patients, even though the benefits of
      this approach remain uncertain. This study retrospectively examined outcomes in a
      cohort of North American PTCL patients treated with both anthracycline- and
      nonanthracycline-containing regimens. The incorporation of anthracycline
      containing regimens was associated with improved progression-free survival (PFS)
      and overall survival (OS). Patients treated with nonanthracycline-containing
      regimens were more likely to have high-risk features and were less likely to
      undergo high-dose therapy and stem cell transplantation. However, anthracycline
      use remained an independent predictor of improved PFS and OS when adjusting for
      these confounding variables. Anthracycline-based regimens and consolidation with
      high-dose therapy and autologous stem cell transplantation in appropriately
      selected patients remains a viable option for patients unable to participate in a
      clinical trial. Long-term disease-free survival is not optimal, highlighting the
      need for an improved understanding of disease pathogenesis, and the development
      of novel therapeutic strategies. 

PMID- 24879116
TI  - Inactivation of BANK1 in a novel IGH-associated translocation t(4;14)(q24;q32)
      suggests a tumor suppressor role in B-cell lymphoma.

PMID- 24879117
TI  - European LeukemiaNet classification intermediate risk-1 cohort is associated with
      poor outcomes in adults with acute myeloid leukemia undergoing allogeneic
      hematopoietic cell transplantation.

PMID- 24879120
TI  - Ultrafast solvation dynamics and charge transfer reactions in room temperature
      ionic liquids.
AB  - Room temperature ionic liquids (ILs) are a new type of solvent with peculiar
      properties. ILs are usually composed of an anion and a bulky cation with one or
      more alkyl chains to decrease the melting point. These structural peculiarities
      lead to the high viscosity and the heterogeneity of ILs, which could affect
      chemical reactions. In the present perspective, we will first introduce the
      experimentally observed nature of the heterogeneous liquid structure and then
      introduce recent developments in the study on electron transfer (ET) and charge
      transfer (CT) reactions in relation with the solvation and the heterogeneity of
      ILs. Because of the high viscosity of ILs, diffusive solvation is expected to be
      slow which could be the rate-limiting factor for ET and CT processes. However,
      ILs could provide a unique reaction field depending on the location of the solute
      within the heterogeneous liquid structure and the reaction could be faster than
      that expected from the bulk viscosity due to the fast fluctuation of the local
      environment. 

PMID- 24879118
TI  - Psychiatric diagnoses, emotional-behavioral symptoms and functional outcomes in
      adolescents born preterm with very low birth weights.
AB  - Children born preterm with very low birth weight (VLBW; birth weight <=1,500 g)
      run risks of neurodevelopmental disorders. Studies of adolescent outcome are
      relatively few. In this follow-up survey, we examined the emotional-behavioral
      symptoms, psychiatric diagnoses and functional status in a geographically-based
      birth cohort of VLBW adolescents (average 13.4 years) as registered in a level
      III center of a recently developed Asian country. Psychiatric interviews were
      conducted. Parents were asked to fill out the Child Behavioral Checklist and the
      Current Status Survey. Results revealed that neonatal survival rate was 75.7%
      (112/148). In the follow-up, 26.2% of the adolescents required individualized
      educational plan; 52.5% were with at least one neuropsychiatric diagnosis (e.g.
      cerebral palsy 24.6%, intellectual disabilities 21.3%, attention
      deficit/hyperactivity disorder 19.7%), and 32.8% of the participants were
      disabled. Logistic regression found that neonatal sepsis and grade III/IV
      intraventricular hemorrhage were most predictive of a disabled status in
      adolescence.

PMID- 24879119
TI  - Accuracy of infrared ear thermometry in children: a meta-analysis and systematic
      review.
AB  - BACKGROUND: Accurate determination of temperature is important, especially in the
      diagnosis and treatment of febrile illnesses in the pediatric population. False
      negative measurement can lead to miss febrile and false positive measurement can
      cause excessive medical care. Temperatures can be measured at various sites, but
      we have not found the ideal thermometer yet. As a relatively new and popular
      alternative over traditional methods, infrared ear thermometry has many
      advantages, but its accuracy remains a major concern. DESIGN: Systematic review
      and meta-analysis. DATA SOURCES: Medline, Ovid, Elsevier, Google Scholar,
      Cochrane Library. STUDY SELECTION: Cross-sectional, prospective design. DATA
      EXTRACTION: Two investigators independently assessed selected studies and
      extracted data. Disagreements were resolved by discussion with other reviewers.
      RESULTS: Mean tympanic temperature was always lower than rectal temperature. The
      overall pooled (random effects) mean difference between tympanic and rectal
      temperature was 0.22 degrees C (95% limits of agreement -0.44 degrees C to 1.30
      degrees C), which is similar to the within rectal device groups (mercury, 0.21
      degrees C, -0.44 degrees C to 1.27 degrees C; electronic, 0.24 degrees C, -0.46
      degrees C to 1.34 degrees C). In febrile children group, the pooled mean
      temperature difference between tympanic and rectal temperature was 0.15 degrees C
      (95% limits of agreement -0.32 degrees C to 1.10 degrees C). CONCLUSION: The mean
      difference was large and the 95% limits of agreement was wide. The accuracy of
      infrared ear thermometry in children is poor, and it cannot replace rectal
      thermometry in clinical practice of children.

PMID- 24879121
TI  - A solvent resistant lab-on-chip platform for radiochemistry applications.
AB  - The application of microfluidics to the synthesis of Positron Emission Tomography
      (PET) tracers has been explored for more than a decade. Microfluidic benefits
      such as superior temperature control have been successfully applied to PET tracer
      synthesis. However, the design of a compact microfluidic platform capable of
      executing a complete PET tracer synthesis workflow while maintaining prospects
      for commercialization remains a significant challenge. This study uses an
      integral system design approach to tackle commercialization challenges such as
      the material to process compatibility with a path towards cost effective lab-on
      chip mass manufacturing from the start. It integrates all functional elements
      required for a simple PET tracer synthesis into one compact radiochemistry
      platform. For the lab-on-chip this includes the integration of on-chip valves, on
      chip solid phase extraction (SPE), on-chip reactors and a reversible fluid
      interface while maintaining compatibility with all process chemicals,
      temperatures and chip mass manufacturing techniques. For the radiochemistry
      device it includes an automated chip-machine interface enabling one-move
      connection of all valve actuators and fluid connectors. A vial-based reagent
      supply as well as methods to transfer reagents efficiently from the vials to the
      chip has been integrated. After validation of all those functional elements, the
      microfluidic platform was exemplarily employed for the automated synthesis of a
      Gastrin-releasing peptide receptor (GRP-R) binding the PEGylated Bombesin BN(7
      14)-derivative ([(18)F]PESIN) based PET tracer. 

PMID- 24879122
TI  - TbKAP6, a mitochondrial HMG box-containing protein in Trypanosoma brucei, is the
      first trypanosomatid kinetoplast-associated protein essential for kinetoplast DNA
      replication and maintenance.
AB  - Kinetoplast DNA (kDNA), the mitochondrial genome of trypanosomatids, is a giant
      planar network of catenated minicircles and maxicircles. In vivo kDNA is
      organized as a highly condensed nucleoprotein disk. So far, in Trypanosoma
      brucei, proteins involved in the maintenance of the kDNA condensed structure
      remain poorly characterized. In Crithidia fasciculata, some small basic histone
      H1-like kinetoplast-associated proteins (CfKAP) have been shown to condense
      isolated kDNA networks in vitro. High-mobility group (HMG) box-containing
      proteins, such as mitochondrial transcription factor A (TFAM) in mammalian cells
      and Abf2 in the budding yeast, have been shown essential for the packaging of
      mitochondrial DNA (mtDNA) into mitochondrial nucleoids, remodeling of
      mitochondrial nucleoids, gene expression, and maintenance of mtDNA. Here, we
      report that TbKAP6, a mitochondrial HMG box-containing protein, is essential for
      parasite cell viability and involved in kDNA replication and maintenance. The RNA
      interference (RNAi) depletion of TbKAP6 stopped cell growth. Replication of both
      minicircles and maxicircles was inhibited. RNAi or overexpression of TbKAP6
      resulted in the disorganization, shrinkage, and loss of kDNA. Minicircle release,
      the first step in kDNA replication, was inhibited immediately after induction of
      RNAi, but it quickly increased 3-fold upon overexpression of TbKAP6. Since the
      release of covalently closed minicircles is mediated by a type II topoisomerase
      (topo II), we examined the potential interactions between TbKAP6 and topo II.
      Recombinant TbKAP6 (rTbKAP6) promotes the topo II-mediated decatenation of kDNA.
      rTbKAP6 can condense isolated kDNA networks in vitro. These results indicate that
      TbKAP6 is involved in the replication and maintenance of kDNA. 

PMID- 24879123
TI  - Distinct innate immune phagocyte responses to Aspergillus fumigatus conidia and
      hyphae in zebrafish larvae.
AB  - Aspergillus fumigatus is the most common filamentous fungal pathogen of
      immunocompromised hosts, resulting in invasive aspergillosis (IA) and high
      mortality rates. Innate immunity is known to be the predominant host defense
      against A. fumigatus; however, innate phagocyte responses to A. fumigatus in an
      intact host and their contributions to host survival remain unclear. Here, we
      describe a larval zebrafish A. fumigatus infection model amenable to real-time
      imaging of host-fungal interactions in live animals. Following infection with A.
      fumigatus, innate phagocyte populations exhibit clear preferences for different
      fungal morphologies: macrophages rapidly phagocytose conidia and form aggregates
      around hyphae, while the neutrophil response is dependent upon the presence of
      hyphae. Depletion of macrophages rendered host larvae susceptible to invasive
      disease. Moreover, a zebrafish model of human leukocyte adhesion deficiency with
      impaired neutrophil function also resulted in invasive disease and impaired host
      survival. In contrast, macrophage-deficient but not neutrophil-deficient larvae
      exhibited attenuated disease following challenge with a less virulent (DeltalaeA)
      strain of A. fumigatus, which has defects in secondary metabolite production.
      Taking these results together, we have established a new vertebrate model for
      studying innate immune responses to A. fumigatus that reveals distinct roles for
      neutrophils and macrophages in mediating host defense against IA. 

PMID- 24879125
TI  - Intracellular beta-glucosidases CEL1a and CEL1b are essential for cellulase
      induction on lactose in Trichoderma reesei.
AB  - Lactose (1,4-O-beta-d-galacto-pyranosyl-d-glucose) induces cellulolytic enzymes
      in Trichoderma reesei and is in fact one of the most important soluble carbon
      sources used to produce cellulases on an industrial level. The mechanism
      underlying the induction is, however, not fully understood. In this study, we
      investigated the cellular functions of the intracellular beta-glucosidases CEL1a
      and CEL1b in the induction of cellulase genes by lactose in T. reesei. We
      demonstrated that while CEL1a and CEL1b were functionally equivalent in mediating
      the induction, the simultaneous absence of these intracellular beta-glucosidases
      abolished cbh1 gene expression on lactose. d-Galactose restored the efficient
      cellulase gene induction in the Deltacel1a strain independently of its reductive
      metabolism, but not in the Deltacel1a Deltacel1b strain. A further comparison of
      the transcriptional responses of the Deltacel1a Deltacel1b strain complemented
      with wild-type CEL1a or a catalytically inactive CEL1a version and the Deltacel1a
      strain constitutively expressing CEL1a or the Kluyveromyces lactis beta
      galactosidase LAC4 showed that both the CEL1a protein and its glycoside
      hydrolytic activity were indispensable for cellulase induction by lactose. We
      also present evidence that intracellular beta-glucosidase-mediated lactose
      induction is further conveyed to XYR1 to ensure the efficiently induced
      expression of cellulase genes. 

PMID- 24879124
TI  - Heterochromatin controls gammaH2A localization in Neurospora crassa.
AB  - In response to genotoxic stress, ATR and ATM kinases phosphorylate H2A in fungi
      and H2AX in animals on a C-terminal serine. The resulting modified histone,
      called gammaH2A, recruits chromatin-binding proteins that stabilize stalled
      replication forks or promote DNA double-strand-break repair. To identify genomic
      loci that might be prone to replication fork stalling or DNA breakage in
      Neurospora crassa, we performed chromatin immunoprecipitation (ChIP) of gammaH2A
      followed by next-generation sequencing (ChIP-seq). gammaH2A-containing
      nucleosomes are enriched in Neurospora heterochromatin domains. These domains are
      comprised of A.T-rich repetitive DNA sequences associated with histone H3
      methylated at lysine-9 (H3K9me), the H3K9me-binding protein heterochromatin
      protein 1 (HP1), and DNA cytosine methylation. H3K9 methylation, catalyzed by DIM
      5, is required for normal gammaH2A localization. In contrast, gammaH2A is not
      required for H3K9 methylation or DNA methylation. Normal gammaH2A localization
      also depends on HP1 and a histone deacetylase, HDA-1, but is independent of the
      DNA methyltransferase DIM-2. gammaH2A is globally induced in dim-5 mutants under
      normal growth conditions, suggesting that the DNA damage response is activated in
      these mutants in the absence of exogenous DNA damage. Together, these data
      suggest that heterochromatin formation is essential for normal DNA replication or
      repair. 

PMID- 24879127
TI  - Structural insights into the cofactor-assisted substrate recognition of yeast
      methylglyoxal/isovaleraldehyde reductase Gre2.
AB  - Saccharomyces cerevisiae Gre2 (EC1.1.1.283) serves as a versatile enzyme that
      catalyzes the stereoselective reduction of a broad range of substrates including
      aliphatic and aromatic ketones, diketones, as well as aldehydes, using NADPH as
      the cofactor. Here we present the crystal structures of Gre2 from S. cerevisiae
      in an apo-form at 2.00A and NADPH-complexed form at 2.40A resolution. Gre2 forms
      a homodimer, each subunit of which contains an N-terminal Rossmann-fold domain
      and a variable C-terminal domain, which participates in substrate recognition.
      The induced fit upon binding to the cofactor NADPH makes the two domains shift
      toward each other, producing an interdomain cleft that better fits the substrate.
      Computational simulation combined with site-directed mutagenesis and enzymatic
      activity analysis enabled us to define a potential substrate-binding pocket that
      determines the stringent substrate stereoselectivity for catalysis. 

PMID- 24879128
TI  - Reading different literature helps one to learn to listen.

PMID- 24879129
TI  - Unequal treatment of human research subjects.
AB  - Unequal treatment of human research subjects is a significant ethical concern,
      because justice in research involving human subjects requires equal protection of
      rights and equal protection from harm and exploitation. Disputes sometimes arise
      concerning the issue of unequal treatment of research subjects. Allegedly unequal
      treatment occurs when subjects are treated differently and there is a genuine
      dispute concerning the appropriateness of equal treatment. Patently unequal
      treatment occurs when subjects are treated differently and there is not a genuine
      dispute about the appropriateness of equal treatment. Allegedly unequal treatment
      will probably always occur in research with human subjects due to disagreements
      about fundamental questions of justice. The best way to deal with allegedly
      unequal treatment is to promote honest and open discussions of the issues at
      stake. Research regulations can help to minimize patently unequal treatment by
      providing rules for investigators, ethical review boards, institutions, and
      sponsors to follow. However, patently unequal treatment may still occur because
      the regulations are subject to interpretation. Federal agencies have provided
      interpretive guidance that can help promote consistent review and oversight of
      human subjects research. Additional direction may be needed on topics that are
      not adequately covered by current guidance or regulations. International
      guidelines can help promote equal treatment of human subjects around the globe.
      While minor variations in the treatment of research subjects should be tolerated
      and even welcomed, major ones (i.e. those that significantly impact human rights
      or welfare) should be avoided or minimized. 

PMID- 24879126
TI  - Insect stage-specific receptor adenylate cyclases are localized to distinct
      subdomains of the Trypanosoma brucei Flagellar membrane.
AB  - Increasing evidence indicates that the Trypanosoma brucei flagellum (synonymous
      with cilium) plays important roles in host-parasite interactions. Several studies
      have identified virulence factors and signaling proteins in the flagellar
      membrane of bloodstream-stage T. brucei, but less is known about flagellar
      membrane proteins in procyclic, insect-stage parasites. Here we report on the
      identification of several receptor-type flagellar adenylate cyclases (ACs) that
      are specifically upregulated in procyclic T. brucei parasites. Identification of
      insect stage-specific ACs is novel, as previously studied ACs were constitutively
      expressed or confined to bloodstream-stage parasites. We show that procyclic
      stage-specific ACs are glycosylated, surface-exposed proteins that dimerize and
      possess catalytic activity. We used gene-specific tags to examine the
      distribution of individual AC isoforms. All ACs examined localized to the
      flagellum. Notably, however, while some ACs were distributed along the length of
      the flagellum, others specifically localized to the flagellum tip. These are the
      first transmembrane domain proteins to be localized specifically at the flagellum
      tip in T. brucei, emphasizing that the flagellum membrane is organized into
      specific subdomains. Deletion analysis reveals that C-terminal sequences are
      critical for targeting ACs to the flagellum, and sequence comparisons suggest
      that differential subflagellar localization might be specified by isoform
      specific C termini. Our combined results suggest insect stage-specific roles for
      a subset of flagellar adenylate cyclases and support a microdomain model for
      flagellar cyclic AMP (cAMP) signaling in T. brucei. In this model, cAMP
      production is compartmentalized through differential localization of individual
      ACs, thereby allowing diverse cellular responses to be controlled by a common
      signaling molecule. 

PMID- 24879130
TI  - Impact of diabetes mellitus on the outcome of pancreatic cancer.
AB  - INTRODUCTION: Diabetes mellitus (DM) has the potential to impact the
      pathogenesis, treatment, and outcome of pancreatic cancer. This study evaluates
      the impact of DM on pancreatic cancer survival. METHODS: We conducted a
      retrospective cohort study from the Veterans Affairs (VA) Central Cancer Registry
      (VACCR) for pancreatic cancer cases between 1995 and 2008. DM and no-DM cases
      were identified from comorbidity data. Univariate and multivariable analysis was
      performed. Multiple imputation method was employed to account for missing
      variables. RESULTS: Of 8,466 cases of pancreatic cancer DM status was known in
      4728 cases that comprised this analysis. Males accounted for 97.7% cases, and 78%
      were white. Overall survival was 4.2 months in DM group and 3.6 months in the no
      DM group. In multivariable analysis, DM had a HR = 0.91 (0.849-0.974). This
      finding persisted after accounting for missing variables using multiple
      imputations method with the HR in DM group of 0.93 (0.867-0.997). CONCLUSIONS:
      Our data suggest DM is associated with a reduction in risk of death in pancreatic
      cancer. Future studies should be directed towards examining this association,
      specifically impact of DM medications on cancer outcome.

PMID- 24879132
TI  - Decision-making in Colorectal Cancer Tumor Board meetings: results of a
      prospective observational assessment.
AB  - BACKGROUND: The management of colorectal cancer increasingly involves
      multidisciplinary tumor boards. In cases where these occur, the quality can be
      variable. Despite this, there are no uniform measures to evaluate them. The aim
      of this study was to evaluate the performance of colorectal cancer tumor boards,
      via real-time prospective observation. METHODS: An observational tool, termed
      Colorectal Multidisciplinary Team Metric for Observation of Decision-Making (cMDT
      MODe), was used to assess decision-making in 267 cases. The presentation of case
      history, radiological and pathological information, as well as contributions to
      decision making of the various team members were analyzed using descriptive
      statistics and t-tests. Interobserver agreement was assessed using
      intraclasscorrelation coefficients. RESULTS: Tumor board meetings lasted 76 min,
      were attended by approximately 16 specialists each, and reviewed an average of 24
      cancer cases (3 min per case review). Regarding the quality of presented
      information to the team, case history information was rated the highest (mean
      4.57), followed by radiological information (mean 4.22) and pathological
      information (mean 3.81). Regarding each team-member's contribution to discussion,
      surgeons were scored the highest (mean 4.81), followed by radiologists (mean
      4.41) and meeting chairs (mean 4.13)--all team members except the board
      coordinators were scored highly. Overall scoring reliability was good (0.79).
      CONCLUSIONS: The cMDT-MODe instrument can be reliably used to prospectively
      assess decision making in the multidisciplinary management of colorectal
      patients. By systematically quantifying the quality of a colorectal cancer tumor
      board, we can identify areas for improving practice so as to optimize decision
      making for cancer care.

PMID- 24879131
TI  - Etiology of childhood diarrhea after rotavirus vaccine introduction: a
      prospective, population-based study in Nicaragua.
AB  - BACKGROUND: Nicaragua was the first developing nation to implement routine
      immunization with the pentavalent rotavirus vaccine (RV5). In this RV5-immunized
      population, understanding infectious etiologies of childhood diarrhea is
      necessary to direct diarrhea treatment and prevention efforts. METHODS: We
      followed a population-based sample of children <5 years in Leon, Nicaragua for
      diarrhea episodes through household visits. Information was obtained on RV5
      history and sociodemographics. Stool samples collected during diarrhea episodes
      and among healthy children underwent laboratory analysis for viral, bacterial and
      parasitic enteropathogens. Detection frequency and incidence of each
      enteropathogen was calculated. RESULTS: The 826 children in the cohort
      experienced 677 diarrhea episodes during 607.5 child-years of exposure time (1.1
      episodes per child-year). At least 1 enteropathogen was detected among 61.1% of
      the 337 diarrheal stools collected. The most common enteropathogens among
      diarrheal stools were: norovirus (20.4%), sapovirus (16.6%), enteropathogenic
      Escherichia coli (11.3%), Entamoeba histolytica/dispar (8.3%), Giardia lamblia
      (8.0%) and enterotoxigenic E. coli (7.7%), with rotavirus detected among 5.3% of
      diarrheal stools. Enteropathogenic Escherichia coli and enterotoxigenic E. coli
      were frequently detected among stools from healthy children. Among children with
      diarrhea, norovirus was more commonly detected among younger children (< 2 years)
      and G. lamblia was more commonly detected among older children (2-4 years). The
      mean age of rotavirus detection was 34.6 months. CONCLUSIONS: In this Central
      American community after RV5 introduction, rotavirus was not commonly detected
      among children with diarrhea. Prevention and appropriate management of norovirus
      and sapovirus should be considered to further reduce the burden of diarrheal
      disease.

PMID- 24879133
TI  - Laparoscopic resection of large gastric GISTs: feasibility and long-term results.
AB  - BACKGROUND: Laparoscopy is the procedure of choice for the resection of gastric
      Gastrointestinal stromal tumors (GISTs) smaller than 2 cm; there is still debate
      regarding the most appropriate operative approach for larger GISTs. The aims of
      this study were to evaluate the safety and long-term efficacy of laparoscopic
      resection of gastric GISTs larger than 2 cm. METHODS: Between 2007 and 2011, we
      prospectively enrolled all patients affected by gastric GIST larger than 2 cm.
      Exclusion criteria for the laparoscopic approach were the presence of metastases
      and the absence of any involvement of the esophago-gastric junction, the pyloric
      canal, or any adjacent organ. Final diagnosis of GIST was confirmed by
      histological and immunohistochemical analysis. Follow-up assessment included
      abdominal CT scans every 6 months for the first 2 years and yearly thereafter.
      RESULTS: Twenty-four consecutive patients were enrolled. Twenty-one patients
      (87.5%) were symptomatic. The most common symptoms were gastrointestinal bleeding
      and abdominal pain. The mean tumor size was 5.51 cm (range 2.5-12.0 cm). GISTs
      were located in the lesser curvature in five cases (20.8%), in the greater
      curvature in seven cases (29.1%), in the posterior wall in one case (4.1%), in
      the anterior wall in eight cases (33.3%), and in the fundus in 3 cases (12.5%).
      Laparoscopic resection was possible in all cases and took on average of 55 min
      (range 30-105 min). Median blood loss was 24 ml. No major intraoperative
      complications were observed. Mortality rate was 0%. Median postoperative stay was
      3 days. No patients were lost to follow-up. No recurrences occurred after a
      median follow-up period of 75 months. CONCLUSION: Although larger randomized
      controlled trials comparing different surgical strategies for large gastric GISTs
      are warranted, our study supports the evidence that laparoscopic resection of
      gastric GISTs is feasible, safe, and effective on long-term clinical outcome even
      for lesions up to 12 cm.

PMID- 24879134
TI  - Univariate and multivariate analyses of preoperative factors influencing
      symptomatic outcomes of transoral fundoplication.
AB  - BACKGROUND: Preoperative factors predicting symptomatic improvement after
      transoral fundoplication (TF) in chronic gastroesophageal reflux disease (GERD)
      patients with persistent symptoms on proton-pump inhibitors (PPIs) therapy have
      not been elucidated fully. METHODS: Univariate and multivariate logistic
      regression analyses were performed on data from 158 consecutive patients who
      underwent TF with the EsophyX device between January 2010 and June 2012 in 14
      community centers. Variables included age, gender, body mass index, GERD
      duration, PPIs therapy duration, presence of hiatal hernia, esophagitis, Hill
      grade, quality of life scores (QOL) on PPIs, % total time pH < 4, and DeMeester
      score on reflux testing off PPIs. RESULTS: All patients suffered from typical
      GERD symptoms. Additionally, 78% (124/158) of patients suffered from atypical
      symptoms. Six percent (10/158) with recurrent GERD symptoms refractory to PPI
      therapy underwent revisional procedure (9 laparoscopic Nissen, 1 TF). Median
      follow-up was 22 (range 10-43) months. For patients with typical symptoms,
      univariate analyses revealed 4 preoperative factors predictive of successful
      outcomes: age >= 50 [odds ratio (OR) = 2.4, 95% confidence interval (CI) = 1.2
      4.8, p = 0.014], GERD Health-related Quality of Life score (GERD-HRQL) >= 15 on
      PPIs (OR = 6.0, CI = 1.2-29.4, p = 0.026, Reflux Symptom Index score > 13 on PPIs
      (OR = 2.4, CI = 1.1-5.2, p = 0.027), and Gastroesophageal Reflux Symptom Score >=
      18 on PPIs (OR = 2.6, CI = 1.2-5.8, p = 0.018). Age and GERD-HRQL score remained
      significant predictors by multivariate analysis. For patients with atypical
      symptoms, only GERD-HRQL score >= 15 on PPIs (OR = 9.9, CI = 0.9-4.6, p = 0.036)
      was associated with successful outcomes. CONCLUSIONS: Elevated preoperative QOL
      scores on PPIs and age >= 50 were most closely associated with successful outcome
      of TF in patients with persistent symptoms despite medical therapy.

PMID- 24879135
TI  - Hand-assisted laparoscopic versus laparoscopy-assisted D2 radical gastrectomy: a
      prospective study.
AB  - BACKGROUD: The feasibility and safety of Hand-assisted laparoscopic D2 radical
      gastrectomy (HALG) have been seldom reported, also, benefits and outcomes are not
      defined. METHODS: We performed a comprehensive and in-depth comparative analysis
      of the general information, the intraoperative data and postoperative data in the
      Group HALG and the Group laparoscopy-assisted D2 radical gastrectomy (LAG).
      RESULTS: The general data of HALG and LAG were no differences (P > 0.05); the
      blood loss and unexpected injury were similar(P > 0.05); the operative time, the
      incision length, the number of lymph nodes recovered, the rate of procedure
      conversion, the amount of postoperative complications, and the length of
      postoperative hospital stay of Group HALG were prior to that of Group LAG(P <
      0.05); there were no differences for the pain score after day 2, the recovery
      time of intestinal function, the rate of reoperation, the 30-day hospital and
      readmission rate(P > 0.05); and there were significant linear correlations
      between the length of postoperative hospital stay and the operative time for both
      groups(P = 0.00). CONCLUSION: Compared with LAG, HALG had similar features of
      being minimally invasive and radical in treating gastric cancers, and HALG was
      safer than LAG.

PMID- 24879137
TI  - Retrograde myotomy: a variation in per oral endoscopic myotomy (POEM) technique.
AB  - BACKGROUND: Per oral endoscopic myotomy (POEM) has evolved as a novel therapeutic
      option for the treatment of esophageal motility disorders such as achalasia. The
      originally described dissection technique involves cutting the inner circular
      esophageal muscle fibers in an antegrade fashion. We have modified this technique
      by commencing the muscular division at the most distal aspect of the submucosal
      tunnel and continuing the dissection in a retrograde fashion. We present our
      initial series of patients performed using this modified technique. METHODS: We
      retrospectively reviewed our prospectively collected database. Peri- and
      postoperative data were collected and analyzed. POEM procedures were performed in
      a near-identical manner as previously published. RESULTS: Retrograde myotomy was
      performed on five patients with a diagnosis of achalasia. Four had a history of
      prior treatment including balloon dilation, with one of these having a prior
      surgical myotomy. Retrograde POEM procedures were performed with trace blood loss
      and without any complications. Mean operative time was 85 min. All patients had
      normal esophagram studies, and diets were advanced as per protocol. CONCLUSION:
      POEM was developed as a minimally invasive method for the treatment of achalasia.
      Our retrograde dissection modification allows the most critical portion of the
      case, namely division of the lower esophageal and upper gastric circular muscle
      fibers, to be performed earlier in the case. This ensures adequate dissection of
      the primary site of esophageal dysfunction should problems arise during the
      procedure. The modification is straightforward, without the need for additional
      training or equipment, and appears to provide a more rapid myotomy with less
      charring in this small cohort of patients.

PMID- 24879136
TI  - Factors contributing to surgical outcomes of transaxillary robotic thyroidectomy
      for papillary thyroid carcinoma.
AB  - INTRODUCTION: Transaxillary robotic thyroidectomy is considered a technically
      feasible and safe treatment option for patients with low-risk papillary thyroid
      carcinoma (PTC). The aim of the present study was to determine the factors that
      contribute to the perioperative surgical outcomes of robotic thyroidectomy and to
      suggest guidelines for patient selection to be used by surgeons inexperienced in
      the technique. METHOD: We reviewed the records of 275 patients with PTC who
      underwent robotic total thyroidectomy using a gasless, transaxillary single
      incision approach at Yonsei University Health System, South Korea, between
      January 2011 and May 2012. The association between surgical outcomes and
      clinicopathologic factors was assessed using linear and logistic regression
      analysis. RESULTS: The contributing factors for surgical outcomes of robotic
      thyroidectomy were categorized as patient factors, including gender and body mass
      index (BMI), and thyroid-specific factors, including thyroid gland size,
      coexistent thyroiditis, tumor size, and serum anti-thyroglobulin antibody and
      anti-microsomal antibody titers. Of these, male gender, a large thyroid gland,
      and thyroiditis significantly increased the total operation time. Male gender,
      thyroiditis, and overweight BMI increased the working space time, and a large
      thyroid gland and overweight BMI affected the console time. A large thyroid gland
      and histological thyroiditis were associated with increased intraoperative blood
      loss. There was no association between postoperative complications and
      clinicopathologic parameters. CONCLUSION: Male gender, overweight BMI, a large
      thyroid gland, and coexistent thyroiditis adversely affected the surgical outcome
      of robotic thyroidectomy. Surgeons inexperienced in the technique should avoid or
      carefully approach individuals with these factors.

PMID- 24879138
TI  - Prospective clinical trial of traction device-assisted endoscopic submucosal
      dissection of large superficial colorectal tumors using the S-O clip.
AB  - BACKGROUND: Endoscopic submucosal dissection (ESD) allows en bloc resection of
      superficial colorectal tumors regardless of size. However, ESD is technically
      difficult, hazardous, and time consuming. New devices may help overcome these
      drawbacks. We focused on traction methods and designed a new traction device, the
      "S-O clip." Its main advantage is that it allows direct visualization of the
      cutting line during submucosal dissection. Moreover, it can be used at any
      location without withdrawing the endoscope. The purpose of this study was to
      evaluate the efficacy and safety of traction device-assisted ESD for large
      colorectal tumors using the S-O clip. METHODS: Between August 2010 and December
      2011, ESD was performed in 70 patients with a superficial colorectal tumor >=20
      mm in diameter in our department. Patients were randomized into two groups: 27
      cases in the S-O clip-assisted ESD group and 23 cases in the conventional ESD
      group. Included in the analysis were patient's gender and age, tumor form, size,
      and location, rate of en bloc resection, procedure time, presence or absence of
      intraoperative perforation or delayed bleeding, and pathological findings.
      Subgroup analysis stratified by these factors and multivariate analyses were
      conducted. RESULTS: In the S-O clip-assisted ESD group, all 27 tumors were
      resected en bloc without any complications. Although a micro perforation occurred
      in one patient in the conventional ESD group, further surgical treatment was not
      required. None of the other 22 cases in the conventional ESD group experienced
      complications. The mean procedure time for the S-O clip-assisted ESD group was
      significantly shorter than for the conventional ESD group (37.4 +/- 32.6 vs. 67.1
      +/- 44.1 min, p = 0.03). No significant between-group differences were found for
      the other factors. CONCLUSION: Our results demonstrated that S-O clip-assisted
      ESD is safe and fast for en bloc resection of large superficial colorectal
      tumors.

PMID- 24879140
TI  - Mapping testicular blood supply in gubernaculum-sparing second-stage Fowler
      Stephens procedure.
AB  - BACKGROUND: Testicular survival following second-stage Fowler-Stephens (FS)
      procedure depends upon adequate arterial supply. There is evidence that
      testicular survival rates are greater following gubernaculum-sparing second-stage
      FS procedure. The importance of collateral vessels in preservation of the testis
      has been hypothesised, but never shown in the literature. We aim to map the
      collateral blood supply to the testicle in gubernaculum-sparing, laparoscopic
      assisted, second-stage FS procedure for intra-abdominal testicles. METHODS:
      Selected patients undergoing a second-stage FS procedure were photographed prior
      to pexy in the Dartos pouch. Photographs were evaluated for the extent of
      vascular collateralisation between gubernacular, deferential and the ligated
      spermatic artery. RESEARCH: Twenty-five patients with 28 undescended testicles
      underwent staged FS procedure over a 7.5-year period between 2005 and April 2013.
      Mean age at operation was 2.44 years, and all testicles were delivered to the
      scrotum. Mean follow-up was 3.29 years, and all patients were reviewed by the
      operating consultant. Testicular survival rate was 100 %. Representative
      photographs clearly demonstrate substantial cremasteric vessels running along the
      gubernaculum with robust collateralisation to the deferential vessel and the
      spermatic arterial stump. CONCLUSION: These images confirm the presence of robust
      collateral between the cremasteric and deferential vessels at second-stage FS
      procedure. Preservation of these collaterals in a gubernaculum-sparing approach
      may explain the excellent results seen in this series.

PMID- 24879139
TI  - NOTES total mesorectal excision (TME) for patients with rectal neoplasia: a
      preliminary experience.
AB  - BACKGROUND: Natural orifice transluminal endoscopic surgery (NOTES) and single
      incision laparoscopy are emerging, minimally invasive techniques. Total
      mesorectal excision (TME), the gold standard treatment for patients with
      resectable distal rectal tumors, is usually performed in an "up-to-down"
      approach, either laparoscopically or via open techniques. A transanal, "down-to
      up" TME has already been reported. Our NOTES variant of TME (NOTESTME) is based
      on a transperineal approach without any form of abdominal assistance. The aim was
      to reduce further the invasiveness of the procedure while optimizing the
      anatomical definition of the distal mesorectum. This approach may lead to reduced
      postoperative pain, decreased hernia formation and improved cosmesis when
      compared to standard laparoscopy. METHODS: NOTESTME was attempted in 16 patients
      with distal rectal neoplasia (i.e., distal edge of the tumor lower than the pouch
      of Douglas, between 0 and 12 cm from the dentate line). Additional inclusion
      criteria consisted of an ASA status <=III and the absence of previous abdominal
      surgery. RESULTS: NOTESTME was completed in all patients. Additional abdominal,
      single-incision laparoscopic assistance was required in 6 (38 %) patients. Mean
      operative time was 265 min (range 155-440 min). The morbidity rate was 18.8 %
      (two small bowel obstructions and one pelvic abscess), requiring re-operation in
      each case. No leaks occurred, and the mortality rate at 30 and 90 days was 0 %.
      Resection margins were negative in all patients. A median of 17 nodes (range 12
      81) was retrieved per specimen. Mean length of hospital stay was 10 days (range 4
      29 days). Patients were followed for an average of 7 months (range 3-23 months).
      CONCLUSION: NOTESTME was feasible and safe in this series of patients with mid-
      or low rectal tumors. The short-term mortality and morbidity rates are
      acceptable, with no apparent compromise in the oncological quality of the
      resection. Larger, randomized controlled trials with long-term follow-up are
      warranted.

PMID- 24879141
TI  - Efficacy and durability of robotic Heller myotomy for achalasia: patient symptoms
      and satisfaction at long-term follow-up.
AB  - BACKGROUND: Laparoscopic Heller myotomy (LHM) has become the standard treatment
      for achalasia in the USA. Robot-assisted Heller myotomy (RHM) has emerged as an
      alternative approach due to improved visualization and fine motor control, but
      long-term follow-up studies have not been reported. We sought to report the long
      term outcomes of RHM and compare them to those of LHM. METHODS: A retrospective
      cohort study was performed for patients who underwent laparoscopic or RHM between
      1995 and 2006. Long-term follow-up was performed via mail or telephone
      questionnaire. The primary outcome measure was durable relief of dysphagia
      without need for further intervention. Secondary outcomes included
      gastroesophageal reflux symptoms, disease-specific quality of life, and patient
      satisfaction with their operation. RESULTS: Seventy-five patients underwent
      laparoscopic (n = 19) or robotic (n = 56) myotomy during the study period. Long
      term follow-up was obtained in 53 (71 %) patients with a median interval of 9
      years. RHM was associated with a decreased mucosal injury rate (0 vs. 16 %, p =
      0.01) and median hospital stay (1 vs. 2 days, p < 0.01) compared to conventional
      laparoscopy. All patients reported initial dysphagia relief, and 80 % required no
      further intervention. This did not differ between groups. Sixty-two percent
      required medications to control reflux symptoms at long-term follow-up, including
      56 % following robotic myotomy and 80 % after laparoscopic myotomy (p = 0.27).
      Overall, 95 % of patients were satisfied with their operation, and 91 % would
      choose surgery again given the benefit of hindsight. CONCLUSION: There is a
      dearth of long-term follow-up data to support the effectiveness of RHM. This
      study demonstrates durable dysphagia relief in the vast majority of patients with
      a high degree of patient satisfaction and a low rate of esophageal mucosal
      injury. While a significant proportion of patients report reflux symptoms, these
      symptoms are well controlled with medical acid suppression.

PMID- 24879144
TI  - Prospective evaluation of simplified algorithm for EUS-guided intra-hepatic
      biliary access and anterograde interventions for failed ERCP.
AB  - BACKGROUND: EUS-guided biliary drainage (EUS-BD) is technically challenging but
      alternative method of therapeutic intervention when ERCP fails. OBJECTIVE: Assess
      the feasibility, safety and risks of EUS-BD with intra-hepatic biliary access and
      anterograde interventions using an algorithm to increase flexibility of
      interventions, limit adverse events and improve procedural time. DESIGN:
      Prospective observational cohort study. PATIENTS: 21 consecutive patients
      underwent EUS-BD drainage for failed ERCP. MAIN OUTCOME MEASURES: Technical and
      clinical success rates with adverse event rate using simplified algorithm.
      RESULTS: Patient recruitment from June 2011-October 2013; mean age of 67.4 years,
      predominantly male (70.5 %) with pancreatic cancer (52.4 %), cholangiocarcinoma
      (14.3 %), other malignant biliary obstruction (9.5 %) and benign biliary
      obstruction (23.8 %). Prior interventions included failed ERCP in 18/21 (85.7 %)
      while 3/21 (14.3 %) had primary EUS-BD. Anterograde cholangiogram was achieved in
      all patients. Technical success was achieved in 20/21 (95.2 %) with clinical
      success was achieved in 19/21 (90.4 %). Placement of access wire was across the
      ampulla in 10/20 (50 %) and into CBD or contra-lateral IHD in 10/20 (50 %). Tract
      dilatation was accomplished in 17/20 (85 %) but required completion using intra
      hepatic needle knife in 3/20 (15 %). Anterograde interventions were performed in
      16/20 (80 %) but crossover to rendezvous in 3/20 (15 %) or choledochoduodenostomy
      1/20 (5 %). Three patients 3/21 (14.3 %) also had endoscopic duodenal SEMS
      placement to relieve duodenal obstruction. Two patients (9.5 %) had post
      procedural bile leak and pain. CONCLUSION: EUS-guided anterograde biliary
      drainage using the intra-hepatic access route has high technical and clinical
      success with low adverse rate. We would promote a simplified standardized
      algorithm, which gives flexibility of direct anterograde interventions.

PMID- 24879143
TI  - Outcomes of laparoscopic cholecystectomy done with surgical energy versus done
      without surgical energy: a prospective-randomized control study.
AB  - OBJECTIVE: Laparoscopic cholecystectomy (LC), a gold standard procedure can be
      done without energized dissection (ED). We did a randomized study for the
      outcomes of LC done with ED or without ED, i.e., with cold dissection (CD).
      METHODS AND PROCEDURES: At a tertiary level institution, open-ended prospective
      randomized control study was conducted between September 2008 and June 2013.
      Consecutive, unselected, consenting candidates for LC were enrolled following
      standard ethics, informed consent, anesthesia, and clinical pathway protocol.
      They were allocated to control group (LC with ED) or study group (LC with CD, as
      per our published technique with the option for rescue ED). The study points were
      based upon Clavien-Dindo grading of postoperative complications. They were
      either, peri-operative events potentially affecting, hospital stay (Grade I) or
      Grade II-V, e.g., peri-operative hemodynamic instability, needing
      intervention/blood transfusion, injury to biliary ducts/hollow viscous,
      postoperative biliary leak, postoperative re-intervention, re-hospitalization,
      mortality, and any adverse event during a 90-day follow-up period. The data were
      prospectively collected in an integrated "hospital information system" that could
      be retrieved only by independent external coordinators. RESULTS: Demographics, co
      morbidities, and gallbladder inflammation profile of the control group (n = 361)
      and study group (n = 384) were comparable. There was no rescue ED usage in the
      study group. Hospital stay (Grade I adverse outcome dependent) was longer, i.e.,
      1.6 +/- 1.03 in the control versus 1.35 +/- 1.2 days in the study group (p <
      0.001). Grade II-IV complications were significantly more (p < 0.009) in control
      group. There was one common bile duct (CBD) injury in each group. The index bilio
      enteric anastomosis for CBD injury in control group failed and needed a revision
      with multiple interventions. There was one grade V adverse outcome, i.e.,
      mortality in the control group. CONCLUSION: Avoiding the use of ED in LC is
      associated with better outcomes.

PMID- 24879142
TI  - Validation of the SF-36 as a measure of postoperative recovery after colorectal
      surgery.
AB  - INTRODUCTION: Surgery is evolving, and new techniques are introduced to improve
      "recovery." Postoperative recovery is complex, and evaluating the effectiveness
      of surgical innovations requires assessment of patient-reported outcomes. The
      Short-Form-36 (SF-36), a generic health-related quality of life questionnaire, is
      the most commonly used instrument in this context. The objective of this study
      was to contribute evidence for the validity of the SF-36 as a metric of
      postoperative recovery. METHODS: Data from 128 patients undergoing planned
      colorectal surgery at one university hospital between 2005 and 2010 were
      analyzed. In the absence of a gold standard, the responsiveness and construct
      validity (known groups and convergent) of the SF-36 were evaluated. Standardized
      response means were computed for the former and non-parametric tests were used to
      assess the statistical significance of the changes observed. Multiple linear
      regression was used to determine whether the SF-36 discriminates between patients
      with versus without complications and between laparoscopic and open surgery
      (known groups); correlations between the SF-36 and the 6-min walk test, a measure
      of functional walking capacity (convergent) was investigated with Spearman's rank
      correlation. RESULTS: The SF-36 was sensitive to clinically important changes.
      Scores on six of eight domains and the physical component summary score
      deteriorated postoperatively (SRM 0.86 for the PCS, p < 0.01) and improved to
      baseline thereafter. Patients with complications had significantly lower scores
      on five SF-36 domains (with differences from -9 (-18, -1), p = 0.04 to -18 (-32, 
      2), p = 0.03), and scores on all subscales were lower than those in a healthy
      population (p < 0.01 to p = 0.04). The SF-36 did not differentiate between
      laparoscopic and open surgery. Physical functioning scores correlated with 6MWT
      distance at 1 and 2 months (Spearman's r = 0.31 and 0.36, p < 0.01). CONCLUSIONS:
      The SF-36 is responsive to expected physiological changes in the postoperative
      period, demonstrates construct validity, and thus constitutes a valid measure of
      postoperative recovery after planned colorectal surgery. The SF-36 did not,
      however, discriminate between recovery after laparoscopic and open surgery.

PMID- 24879146
TI  - ATG13: just a companion, or an executor of the autophagic program?
AB  - During the past 20 years, autophagy signaling has entered the main stage of the
      cell biological theater. Autophagy represents an intracellular degradation
      process that is involved in both the bulk recycling of cytoplasmic components and
      the selective removal of organelles, protein aggregates, or intracellular
      pathogens. The understanding of autophagy has been greatly facilitated by the
      characterization of the molecular machinery governing this process. In yeast,
      initiation of autophagy is controlled by the Atg1 kinase complex, which is
      composed of the Ser/Thr kinase Atg1, the adaptor protein Atg13, and the ternary
      complex of Atg17-Atg31-Atg29. In vertebrates, the orthologous ULK1 kinase complex
      contains the Ser/Thr kinase ULK1 and the accessory proteins ATG13, RB1CC1, and
      ATG101. Among these components, Atg1/ULK1 have gained major attention in the
      past, i.e., for the identification of upstream regulatory kinases, the
      characterization of downstream substrates controlling the autophagic flux, or as
      a druggable target for the modulation of autophagy. However, accumulating data
      indicate that the function of Atg13/ATG13 has been likely underestimated so far.
      In addition to ensuring proper Atg1/ULK1 recruitment and activity, this adaptor
      molecule has been implicated in ULK1-independent autophagy processes.
      Furthermore, recent data have identified additional binding partners of
      Atg13/ATG13 besides the components of the Atg1/ULK1 complex, e.g., Atg8 family
      proteins or acidic phospholipids. Therefore, in this review we will center the
      spotlight on Atg13/ATG13 and summarize the role that Atg13/ATG13 assumes in the
      autophagy stage play. 

PMID- 24879147
TI  - Identification of a novel MTOR activator and discovery of a competing endogenous
      RNA regulating autophagy in vascular endothelial cells.
AB  - MTOR, a central regulator of autophagy, is involved in cancer and cardiovascular
      and neurological diseases. Modulating the MTOR signaling balance could be of
      great significance for numerous diseases. No chemical activators of MTOR have
      been found, and the urgent challenge is to find novel MTOR downstream components.
      In previous studies, we found a chemical small molecule, 3-benzyl-5-((2
      nitrophenoxy) methyl)-dihydrofuran-2(3H)-one (3BDO), that inhibited autophagy in
      human umbilical vein endothelial cells (HUVECs) and neuronal cells. Here, we
      found that 3BDO activated MTOR by targeting FKBP1A (FK506-binding protein 1A, 12
      kDa). We next used 3BDO to detect novel factors downstream of the MTOR signaling
      pathway. Activation of MTOR by 3BDO increased the phosphorylation of TIA1 (TIA1
      cytotoxic granule-associated RNA binding protein/T-cell-restricted intracellular
      antigen-1). Finally, we used gene microarray, RNA interference, RNA-ChIP assay,
      bioinformatics, luciferase reporter assay, and other assays and found that 3BDO
      greatly decreased the level of a long noncoding RNA (lncRNA) derived from the 3'
      untranslated region (3'UTR) of TGFB2, known as FLJ11812. TIA1 was responsible for
      processing FLJ11812. Further experiments results showed that FLJ11812 could bind
      with MIR4459 targeting ATG13 (autophagy-related 13), and ATG13 protein level was
      decreased along with 3BDO-decreased FLJ11812 level. Here, we provide a new
      activator of MTOR, and our findings highlight the role of the lncRNA in
      autophagy. 

PMID- 24879148
TI  - Small molecule-driven mitophagy-mediated NLRP3 inflammasome inhibition is
      responsible for the prevention of colitis-associated cancer.
AB  - Nonresolving inflammation in the intestine predisposes individuals to the
      development of colitis-associated cancer (CAC). Inflammasomes are thought to
      mediate intestinal homeostasis, and their dysregulation contributes to
      inflammatory bowel diseases and CAC. However, few agents have been reported to
      reduce CAC by targeting inflammasomes. Here we show that the small molecule
      andrographolide (Andro) protects mice against azoxymethane/dextran sulfate sodium
      induced colon carcinogenesis through inhibiting the NLRP3 inflammasome.
      Administration of Andro significantly attenuated colitis progression and tumor
      burden. Andro also inhibited NLRP3 inflammasome activation in macrophages both in
      vivo and in vitro, as indicated by reduced expression of cleaved CASP1,
      disruption of NLRP3-PYCARD-CASP1 complex assembly, and lower IL1B secretion.
      Importantly, Andro was found to trigger mitophagy in macrophages, leading to a
      reversed mitochondrial membrane potential collapse, which in turn inactivated the
      NLRP3 inflammasome. Moreover, downregulation of the PIK3CA-AKT1-MTOR-RPS6KB1
      pathway accounted for Andro-induced autophagy. Finally, Andro-driven inhibition
      of the NLRP3 inflammasome and amelioration of murine models for colitis and CAC
      were significantly blocked by BECN1 knockdown, or by various autophagy
      inhibitors. Taken together, our findings demonstrate that mitophagy-mediated
      NLRP3 inflammasome inhibition by Andro is responsible for the prevention of CAC.
      Our data may help guide decisions regarding the use of Andro in patients with
      inflammatory bowel diseases, which ultimately reduces the risk of CAC. 

PMID- 24879149
TI  - The role of GABARAPL1/GEC1 in autophagic flux and mitochondrial quality control
      in MDA-MB-436 breast cancer cells.
AB  - GABARAPL1/GEC1 is an early estrogen-induced gene which encodes a protein highly
      conserved from C. elegans to humans. Overexpressed GABARAPL1 interacts with GABAA
      or kappa opioid receptors, associates with autophagic vesicles, and inhibits
      breast cancer cell proliferation. However, the function of endogenous GABARAPL1
      has not been extensively studied. We hypothesized that GABARAPL1 is required for
      maintaining normal autophagic flux, and plays an important role in regulating
      cellular bioenergetics and metabolism. To test this hypothesis, we knocked down
      GABARAPL1 expression in the breast cancer MDA-MB-436 cell line by shRNA.
      Decreased expression of GABARAPL1 activated procancer responses of the MDA-MB-436
      cells including increased proliferation, colony formation, and invasion. In
      addition, cells with decreased expression of GABARAPL1 exhibited attenuated
      autophagic flux and a decreased number of lysosomes. Moreover, decreased
      GABARAPL1 expression led to cellular bioenergetic changes including increased
      basal oxygen consumption rate, increased intracellular ATP, increased total
      glutathione, and an accumulation of damaged mitochondria. Taken together, our
      results demonstrate that GABARAPL1 plays an important role in cell proliferation,
      invasion, and autophagic flux, as well as in mitochondrial homeostasis and
      cellular metabolic programs. 

PMID- 24879150
TI  - UCHL1 deficiency exacerbates human islet amyloid polypeptide toxicity in beta
      cells: evidence of interplay between the ubiquitin/proteasome system and
      autophagy.
AB  - The islet in type 2 diabetes mellitus (T2DM) is characterized by a deficit in
      beta-cells and increased beta-cell apoptosis attributable at least in part to
      intracellular toxic oligomers of IAPP (islet amyloid polypeptide). beta-cells of
      individuals with T2DM are also characterized by accumulation of polyubiquitinated
      proteins and deficiency in the deubiquitinating enzyme UCHL1 (ubiquitin carboxyl
      terminal esterase L1 [ubiquitin thiolesterase]), accounting for a dysfunctional
      ubiquitin/proteasome system. In the present study, we used mouse genetics to
      elucidate in vivo whether a partial deficit in UCHL1 enhances the vulnerability
      of beta-cells to human-IAPP (hIAPP) toxicity, and thus accelerates diabetes
      onset. We further investigated whether a genetically induced deficit in UCHL1
      function in beta-cells exacerbates hIAPP-induced alteration of the autophagy
      pathway in vivo. We report that a deficit in UCHL1 accelerated the onset of
      diabetes in hIAPP transgenic mice, due to a decrease in beta-cell mass caused by
      increased beta-cell apoptosis. We report that UCHL1 dysfunction aggravated the
      hIAPP-induced defect in the autophagy/lysosomal pathway, illustrated by the
      marked accumulation of autophagosomes and cytoplasmic inclusions positive for
      SQSTM1/p62 and polyubiquitinated proteins with lysine 63-specific ubiquitin
      chains. Collectively, this study shows that defective UCHL1 function may be an
      early contributor to vulnerability of pancreatic beta-cells for protein
      misfolding and proteotoxicity, hallmark defects in islets of T2DM. Also, given
      that deficiency in UCHL1 exacerbated the defective autophagy/lysosomal
      degradation characteristic of hIAPP proteotoxicity, we demonstrate a previously
      unrecognized role of UCHL1 in the function of the autophagy/lysosomal pathway in
      beta-cells. 

PMID- 24879151
TI  - Disruption of chaperone-mediated autophagy-dependent degradation of MEF2A by
      oxidative stress-induced lysosome destabilization.
AB  - Oxidative stress has been implicated in both normal aging and various
      neurodegenerative disorders and it may be a major cause of neuronal death.
      Chaperone-mediated autophagy (CMA) targets selective cytoplasmic proteins for
      degradation by lysosomes and protects neurons against various extracellular
      stimuli including oxidative stress. MEF2A (myocyte enhancer factor 2A), a key
      transcription factor, protects primary neurons from oxidative stress-induced cell
      damage. However, the precise mechanisms of how the protein stability and the
      transcriptional activity of MEF2A are regulated under oxidative stress remain
      unknown. In this study, we report that MEF2A is physiologically degraded through
      the CMA pathway. In pathological conditions, mild oxidative stress (200 MUM H 2O
      2) enhances the degradation of MEF2A as well as its activity, whereas excessive
      oxidative stress (> 400 MUM H 2O 2) disrupts its degradation process and leads to
      the accumulation of nonfunctional MEF2A. Under excessive oxidative stress, an N
      terminal HDAC4 (histone deacetylase 4) cleavage product (HDAC4-NT), is
      significantly induced by lysosomal serine proteases released from ruptured
      lysosomes in a PRKACA (protein kinase, cAMP-dependent, catalytic, alpha)
      independent manner. The production of HDAC4-NT, as a MEF2 repressor, may account
      for the reduced DNA-binding and transcriptional activity of MEF2A. Our work
      provides reliable evidence for the first time that MEF2A is targeted to lysosomes
      for CMA degradation; oxidative stress-induced lysosome destabilization leads to
      the disruption of MEF2A degradation as well as the dysregulation of its function.
      These findings may shed light on the underlying mechanisms of pathogenic
      processes of neuronal damage in various neurodegenerative-related diseases. 

PMID- 24879152
TI  - Phosphorylation of NBR1 by GSK3 modulates protein aggregation.
AB  - The autophagy receptor NBR1 (neighbor of BRCA1 gene 1) binds UB/ubiquitin and the
      autophagosome-conjugated MAP1LC3/LC3 (microtubule-associated protein 1 light
      chain 3) proteins, thereby ensuring ubiquitinated protein degradation. Numerous
      neurodegenerative and neuromuscular diseases are associated with inappropriate
      aggregation of ubiquitinated proteins and GSK3 (glycogen synthase kinase 3)
      activity is involved in several of these proteinopathies. Here we show that NBR1
      is a substrate of GSK3. NBR1 phosphorylation by GSK3 at Thr586 prevents the
      aggregation of ubiquitinated proteins and their selective autophagic degradation.
      Indeed, NBR1 phosphorylation decreases protein aggregation induced by puromycin
      or by the DES/desmin N342D mutant found in desminopathy patients and stabilizes
      ubiquitinated proteins. Importantly, decrease of protein aggregates is due to an
      inhibition of their formation and not to their autophagic degradation as
      confirmed by data on Atg7 knockout mice. The relevance of NBR1 phosphorylation in
      human pathology was investigated. Analysis of muscle biopsies of sporadic
      inclusion body myositis (sIBM) patients revealed a strong decrease of NBR1
      phosphorylation in muscles of sIBM patients that directly correlated with the
      severity of protein aggregation. We propose that phosphorylation of NBR1 by GSK3
      modulates the formation of protein aggregates and that this regulation mechanism
      is defective in a human muscle proteinopathy. 

PMID- 24879154
TI  - DIRAS3 regulates the autophagosome initiation complex in dormant ovarian cancer
      cells.
AB  - DIRAS3 is an imprinted tumor suppressor gene that is downregulated in 60% of
      human ovarian cancers. Re-expression of DIRAS3 at physiological levels inhibits
      proliferation, decreases motility, induces autophagy, and regulates tumor
      dormancy. Functional inhibition of autophagy with choroquine in dormant
      xenografts that express DIRAS3 significantly delays tumor regrowth after DIRAS3
      levels are reduced, suggesting that autophagy sustains dormant ovarian cancer
      cells. This study documents a newly discovered role for DIRAS3 in forming the
      autophagosome initiation complex (AIC) that contains BECN1, PIK3C3, PIK3R4,
      ATG14, and DIRAS3. Participation of BECN1 in the AIC is inhibited by binding of
      BECN1 homodimers to BCL2. DIRAS3 binds BECN1, disrupting BECN1 homodimers and
      displacing BCL2. Binding of DIRAS3 to BECN1 increases the association of BECN1
      with PIK3C3 and ATG14, facilitating AIC activation. Amino acid starvation of
      cells induces DIRAS3 expression, reduces BECN1-BCL2 interaction and promotes
      autophagy, whereas DIRAS3 depletion blocks amino acid starvation-induced
      autophagy. In primary ovarian cancers, punctate expression of DIRAS3, BECN1, and
      the autophagic biomarker MAP1LC3 are highly correlated (P<0.0001), underlining
      the clinical relevance of these mechanistic studies. Punctate expression of
      DIRAS3 and MAP1LC3 was detected in only 21-23% of primary ovarian cancers but in
      81-84% of tumor nodules found on the peritoneal surface at second-look operations
      following primary chemotherapy. This reflects a 4-fold increase (P<0.0001) in
      autophagy between primary disease and post-treatment recurrence. We suggest that
      DIRAS3 not only regulates the AIC, but induces autophagy in dormant, nutrient
      deprived ovarian cancer cells that remain after conventional chemotherapy,
      facilitating their survival. 

PMID- 24879155
TI  - Identification of Atg3 as an intrinsically disordered polypeptide yields insights
      into the molecular dynamics of autophagy-related proteins in yeast.
AB  - The mechanism of autophagy relies on complex cell signaling and regulatory
      processes. Each cell contains many proteins that lack a rigid 3-dimensional
      structure under physiological conditions. These dynamic proteins, called
      intrinsically disordered proteins (IDPs) and protein regions (IDPRs), are
      predominantly involved in cell signaling and regulation. Yet, very little is
      known about their presence among proteins of the core autophagy machinery. In
      this work, we characterized the autophagy protein Atg3 from yeast and human along
      with 2 variants to show that Atg3 is an IDPRs-containing protein and that
      disorder/order predicted for these proteins from their amino acid sequence
      corresponds to their experimental characteristics. Based on this consensus, we
      applied the same prediction methods to all known Atg proteins from Saccharomyces
      cerevisiae. The data presented here provide an insight into the structural
      dynamics of each Atg protein. They also show that intrinsic disorder at various
      levels has to be taken into consideration for about half of the Atg proteins.
      This work should become a useful tool that will facilitate and encourage
      exploration of protein intrinsic disorder in autophagy. 

PMID- 24879153
TI  - A nonapoptotic role for CASP2/caspase 2: modulation of autophagy.
AB  - CASP2/caspase 2 plays a role in aging, neurodegeneration, and cancer. The
      contributions of CASP2 have been attributed to its regulatory role in apoptotic
      and nonapoptotic processes including the cell cycle, DNA repair, lipid
      biosynthesis, and regulation of oxidant levels in the cells. Previously, our lab
      demonstrated CASP2-mediated modulation of autophagy during oxidative stress. Here
      we report the novel finding that CASP2 is an endogenous repressor of autophagy.
      Knockout or knockdown of CASP2 resulted in upregulation of autophagy in a variety
      of cell types and tissues. Reinsertion of Caspase-2 gene (Casp2) in mouse
      embryonic fibroblast (MEFs) lacking Casp2 (casp2(-/-)) suppresses autophagy,
      suggesting its role as a negative regulator of autophagy. Loss of CASP2-mediated
      autophagy involved AMP-activated protein kinase, mechanistic target of rapamycin,
      mitogen-activated protein kinase, and autophagy-related proteins, indicating the
      involvement of the canonical pathway of autophagy. The present study also
      demonstrates an important role for loss of CASP2-induced enhanced reactive oxygen
      species production as an upstream event in autophagy induction. Additionally, in
      response to a variety of stressors that induce CASP2-mediated apoptosis, casp2(-/
      ) cells demonstrate a further upregulation of autophagy compared with wild-type
      MEFs, and upregulated autophagy provides a survival advantage. In conclusion, we
      document a novel role for CASP2 as a negative regulator of autophagy, which may
      provide important insight into the role of CASP2 in various processes including
      aging, neurodegeneration, and cancer. 

PMID- 24879156
TI  - BECN1 is involved in the initiation of mitophagy: it facilitates PARK2
      translocation to mitochondria.
AB  - The autophagy protein BECN1/Beclin 1 is known to play a central role in
      autophagosome formation and maturation. The results presented here demonstrate
      that BECN1 interacts with the Parkinson disease-related protein PARK2. This
      interaction does not require PARK2 translocation to mitochondria and occurs
      mostly in cytosol. However, our results suggest that BECN1 is involved in PARK2
      translocation to mitochondria because loss of BECN1 inhibits CCCP- or PINK1
      overexpression-induced PARK2 translocation. Our results also demonstrate that the
      observed PARK2-BECN1 interaction is functionally important. Measurements of the
      level of MFN2 (mitofusin 2), a PARK2 substrate, demonstrate that depletion of
      BECN1 prevents PARK2 translocation-induced MFN2 ubiquitination and loss. BECN1
      depletion also rescues the MFN2 loss-induced suppression of mitochondrial fusion.
      In sum, our results demonstrate that BECN1 interacts with PARK2 and regulates
      PARK2 translocation to mitochondria as well as PARK2-induced mitophagy prior to
      autophagosome formation. 

PMID- 24879158
TI  - Restarting stalled autophagy a potential therapeutic approach for the lipid
      storage disorder, Niemann-Pick type C1 disease.
AB  - Autophagy is essential for cellular homeostasis and its dysfunction in human
      diseases has been implicated in the accumulation of misfolded protein and in
      cellular toxicity. We have recently shown impairment in autophagic flux in the
      lipid storage disorder, Niemann-Pick type C1 (NPC1) disease associated with
      abnormal cholesterol sequestration, where maturation of autophagosomes is
      impaired due to defective amphisome formation caused by failure in SNARE
      machinery. Abrogation of autophagy also causes cholesterol accumulation,
      suggesting that defective autophagic flux in NPC1 disease may act as a primary
      causative factor not only by imparting its deleterious effects, but also by
      increasing cholesterol load. However, cholesterol depletion treatment with HP
      beta-cyclodextrin impedes autophagy, whereas pharmacologically stimulating
      autophagy restores its function independent of amphisome formation. Of potential
      therapeutic relevance is that a low dose of HP-beta-cyclodextrin that does not
      perturb autophagy, coupled with an autophagy inducer, may rescue both the
      cholesterol and autophagy defects in NPC1 disease.

PMID- 24879157
TI  - Development of potent autophagy inhibitors that sensitize oncogenic BRAF V600E
      mutant melanoma tumor cells to vemurafenib.
AB  - Autophagy is a dynamic cell survival mechanism by which a double-membrane
      vesicle, or autophagosome, sequesters portions of the cytosol for delivery to the
      lysosome for recycling. This process can be inhibited using the antimalarial
      agent chloroquine (CQ), which impairs lysosomal function and prevents
      autophagosome turnover. Despite its activity, CQ is a relatively inadequate
      inhibitor that requires high concentrations to disrupt autophagy, highlighting
      the need for improved small molecules. To address this, we screened a panel of
      antimalarial agents for autophagy inhibition and chemically synthesized a novel
      series of acridine and tetrahydroacridine derivatives. Structure-activity
      relationship studies of the acridine ring led to the discovery of VATG-027 as a
      potent autophagy inhibitor with a high cytotoxicity profile. In contrast, the
      tetrahydroacridine VATG-032 showed remarkably little cytotoxicity while still
      maintaining autophagy inhibition activity, suggesting that both compounds act as
      autophagy inhibitors with differential effects on cell viability. Further,
      knockdown of autophagy-related genes showed no effect on cell viability,
      demonstrating that the ability to inhibit autophagy is separate from the compound
      cytotoxicity profiles. Next, we determined that both inhibitors function through
      lysosomal deacidification mechanisms and ultimately disrupt autophagosome
      turnover. To evaluate the genetic context in which these lysosomotropic
      inhibitors may be effective, they were tested in patient-derived melanoma cell
      lines driven by oncogenic BRAF (v-raf murine sarcoma viral oncogene homolog B).
      We discovered that both inhibitors sensitized melanoma cells to the BRAF V600E
      inhibitor vemurafenib. Overall, these autophagy inhibitors provide a means to
      effectively block autophagy and have the potential to sensitize mutant BRAF
      melanomas to first-line therapies. 

PMID- 24879159
TI  - Deficient autophagy unravels the ROS paradox in chronic granulomatous disease.
AB  - Autophagy defects resulting in inflammation appear to be a key feature in the
      pathogenesis of Crohn colitis. An inflammatory colitis indistinguishable from
      Crohn disease is described in patients with chronic granulomatous disease (CGD).
      Patients with CGD have a mutated NADPH complex and are therefore deficient in
      reactive oxygen species (ROS) production; however, the underlying mechanism for
      the inflammatory colitis in CGD remained unknown. In a recent study, our group
      reported that NADPH-dependent ROS deficiency results in autophagic dysfunction
      that subsequently contributes to increased IL1B/interleukin 1beta production.
      Mice deficient in the NADPH-complex component NCF4/p40phox, and CGD patients with
      a defect in NCF4 display minimal recruitment of LC3 to phagosomes in response to
      internalized bacteria and fungi. Human monocytes from patients with CGD with
      defective LC3 recruitment show increased IL1B production after LPS stimulation.
      Blocking IL1 protects NCF4-deficient mice from experimental colitis; importantly,
      improved clinical outcome in 2 CGD patients with colitis is also observed with
      IL1 blockade. Moreover, blocking IL1 restores defective autophagy in CGD mice and
      cells from patients with CGD. Thus, autophagic dysfunction underlies the
      pathogenesis of granulomatous colitis in CGD, and blocking IL1 can be used to
      treat CGD colitis. 

PMID- 24879161
TI  - Autophagy side of MB21D1/cGAS DNA sensor.
AB  - The MB21D1/cGAS (Mab-21 domain-containing 1/cyclic GMP-AMP [cGAMP] synthetase),
      acts as an intracellular pattern recognition receptor (PPR) to sense cytosolic
      pathogen DNAs and subsequently generates the second messenger cGAMP to initiate
      the TMEM173/STING pathway for interferon (IFN) production. Intriguingly, we have
      recently demonstrated crosstalk between the intracellular DNA sensing pathway and
      autophagy machinery by demonstrating a direct interaction between the MB21D1 DNA
      sensor and the BECN1/Beclin 1 autophagy protein. This interaction not only
      suppresses MB21D1 enzymatic activity to halt cGAMP production, but also enhances
      the autophagy-mediated degradation of cytosolic microbial DNAs. This demonstrates
      that MB21D1 is the molecular link between the intracellular DNA sensing pathway
      and the autophagy pathway, ultimately developing well-balanced immune responses
      against pathogens. 

PMID- 24879162
TI  - [Discordance between spine and hip Bone Mineral Density measurement using DXA in
      osteoporosis diagnosis: prevalence and risk factors].
AB  - BACKGROUND: Diagnostic discordance for osteoporosis is the presence of different
      categories of T-scores in 2 skeletal sites of an individual patient, falling into
      2 different diagnostic categories identified by the World Health Organization
      classification. AIM: To determinate the prevalence and risk factors for T-score
      discordance between spine and hip measurement sites. METHODS: Demographic data,
      anthropometric measurements, and risk factors for osteoporosis were derived from
      a database of 1780 patients referred to the outpatient osteoporosis testing
      center of the departement of Rheumatology between September 2006 and February
      2010. Bone mineral density (BMD) was performed by Dual-energy x-ray
      absorptiometry (DXA) on L1-L4 lumbar spine and total hips for all cases. Minor
      discordance was considered when the difference between 2 sites was no more than 1
      World Health Organization diagnostic class. Major discordance was present when 1
      site is osteoporotic and the other is normal. RESULTS: In 1780 participants (1606
      women and 174 males; mean age, 59.5 +/- 14.3 years), concordance of T-scores,
      minor discordance, and major discordance were seen in 49.4%, 45.7%, and 4.8% of
      the cases, respectively. In both minor and major discordance BMD was lower in
      lumbar spine than total hips. In univariate and multivariate logistic regression
      analysis only menopause was identified as risk factors against T-score
      discordance with p<0.001 and [OR=5.47; IC: 2.61- 12.79]. The others factors: age,
      gender, BMI, fracture history, corticotherapy, rheumatoid arthritis, tobacco and
      diabetes were not associated with the T-score discordance. CONCLUSION: Clinicians
      should expect that at least half of patients tested by DXA will demonstrate T
      score discordance between spine and total hip measurement sites. T-score
      discordance can occur for a variety of reasons related to physiologic and
      pathologic patient factors as well as the performance or analysis of DXA itself.

PMID- 24879160
TI  - A histone point mutation that switches on autophagy.
AB  - The multifaceted process of aging inevitably leads to disturbances in cellular
      metabolism and protein homeostasis. To meet this challenge, cells make use of
      autophagy, which is probably one of the most important pathways preserving
      cellular protection under stressful conditions. Thus, efficient autophagic flux
      is required for healthy aging in many if not all eukaryotic organisms. The
      regulation of autophagy itself is affected by changing metabolic conditions, but
      the precise metabolic circuitries are poorly understood. Recently, we found that
      the nucleocytosolic pool of acetyl-coenzyme A (AcCoA) functions as a major and
      dominant suppressor of cytoprotective autophagy during aging. Here, we propose an
      epigenetic mechanism for AcCoA-mediated autophagy suppression that causally
      involves the regulation of histone acetylation and changes in the autophagy
      relevant transcriptome. 

PMID- 24879163
TI  - [Pleural complications of pulmonary hydatid disease].
AB  - BACKGROUND: Pulmonary hydatid disease encountered in Tunisia frequentely. Rupture
      of pulmonary cyst into the pleural cavity is rare, but represents the most
      serious complication of the hydatid disease. AIM: We analyse clinical, radiologic
      and outcome of intrapleural rupture of lung hydatic cyst and evaluate our
      experience in the surgical treatment. METHODS: We report 5 cases of rupture of
      rupture of pulmonary hydatid cyst into the pleural cavity hospitilazed during
      1995 to 2010. RESULTS: Mean age of patients was 22,4 years. Three patients
      presented with hydropneumothorax, one with spontaneous pneumothorax and one with
      haemoptysis. The diagnosis was determined peropreratively in the first case and
      based on radiographic and serology findings in the other cases. Surgical
      treatment consist on decortication and cystotomy with capitonnage in three cases,
      pleurectomy one and lobectomy in the other case. Post operative course was
      unventful in four cases, one patient had bronchopleural fistula, pneumothorax and
      wound infection (parietal abssess) resolved with local treatment. After surgery,
      all patients were treated in post operative by 3 months course with Albendazole
      chemotherapy with a favourable outcome. CONCLUSION: Rupture of a pulmonary cyst
      into the pleural cavity is rare, but represents the most serious complication of
      the hydatid disease. The therapeutic progress has improved the prognosis of
      intrapleural ruptured hydatid cysts.

PMID- 24879164
TI  - [Symptoms and natural history of hospital chronic obstructive pulmonary disease].
AB  - BACKGROUND: Since few years, the data describing the chronic obstructive
      pulmonary disease (COPD) have changed and new concepts have emerged. AIM: To
      study the clinical characteristics and outcome of patients with COPD in a
      Tunisian population. METHODS: It is a retrospective study including 150 patients
      with COPD admitted at the pulmonary department of Charles Nicolle Hospital in
      Tunis, during a period of ten years. RESULTS: Data from 150 patients hospitalized
      at the pulmonary department of Charles Nicolle Hospital in Tunis, were analyzed.
      They were 126 men and 24 women with a mean age of 67 years. Tobacco was the
      predominant risk factor. Eighty-two (55%) patients were classified GOLD stage IV
      at diagnosis. The number of exacerbation varied from 1 to 7 with an average
      higher in patients classified as stage IV (p = 0.007). CONCLUSION: The COPD is
      pathology of smoking men. Comorbidities and exacerbations prevalence increase
      according the disease severity. In fact, better knowledge of exacerbations
      etiologies allows considering better measurement of prevention.

PMID- 24879165
TI  - [Prevalence of anxiety and depressive disorders among the nurses of Sousse Farhat
      Hached hospital: assessment by the Tunisian version of CIDI].
AB  - BACKGROUND: Stress is a part of the nursing profession and it is reflected in
      higher rates of depression and anxiety disorders. aim : This study aimed to
      determine the prevalence of major depression episodes (MDE), Dysthymia and
      generalized anxiety disorder (GAD), as well as their associated factors, in a
      representative sample of nurses in Sousse Farhat Hached teaching hospital, using
      the Tunisian version of CIDI. METHODS: It's a descriptive study, carried out
      among a representative sample of the nursing staff of Sousse Farhat Hached
      teaching hospital (N=228). The data obtained was the result of an interview using
      the CIDI sections related to MDD, dysthymia and GAD. Sociodemographic, medical
      and professional data were also collected. RESULTS: The MDE prevalence was
      estimated at 7.5% and was associated with the female gender, the remoteness of
      the workplace, the number of persons on the participant's charge, the personal
      antecedents of mental and organic pathologies, the job satisfaction related to
      internal relationships and security as well as with the wish to change position.
      The prevalence of Dysthymia was 5.7% and was associated with family antecedents
      of mental pathologies. The prevalence of TAG (4.4%) was associated with
      remoteness of the workplace, personal antecedents of mental pathologies and with
      satisfaction related to material conditions. CONCLUSION: The important issues of
      human and financial consequences of stress at work require the use of large-scale
      measures that should be incorporated into a strategy covering all factors and
      involving both health authorities and administrative occupational medicine.

PMID- 24879166
TI  - [Cerebral imaging in epileptic children: study of 140 cases].
AB  - BACKGROUND: Epilepsy is a chronic disease, often with an onset during childhood
      and characterized by spontaneous and recurrent seizures. It concerns 0.5-1% of
      children under 16 years of age. Being much more sensitive than computed
      tomography, magnetic resonance imaging is the technique of choice to identify an
      underlying cause. CT scan is used in emergency situations. AIM: To describe
      cerebral lesions in epilepetic children and to identify predicative factors of
      abnormal neuroimaging. METHODS: Authors present a retrospective descriptive study
      of Neuroimaging data of 140 epileptic children evaluated for a period from 2000
      2007 in the paediatric departement of Sfax. RESULTS: The mean age at onset of
      seizures was 3 years. The sex ratio was 1.12. Psychomotor retardation was noted
      in 75 patients. The seizures were generalized in 75% of case. Neurological
      examination was abnormal in 73 cases (52%). The main indications for conducting a
      brain imaging were psychomotor retardation (65 cases) and focal onset seizures
      (25 cases). Anoxo-ischemic lesions were the most frequent cerebral anomalies
      followed by brain malformations. Predictors of pathological MRI were an age at
      onset of seizure <3 years, psychomotor retardation and abnormal neurological
      examination. CONCLUSION: The morphological imaging is recommended for recent
      seizures of the child with the exception of idiopathic epilepsies. MRI is the
      best imaging modality in exploration of epilepsy in this context.

PMID- 24879167
TI  - Lidocaine reduces endotracheal tube associated side effects when instilled over
      the glottis but not when used to inflate the cuff: A double blind, placebo
      controlled, randomized trial.
AB  - BACKGROUND: Tracheal intubation results in an alteration of the laryngeal mucosa
      which can lead to undesirable effects at emergence from anaesthesia. Local
      anesthetics, when administered topically, may represent an interesting
      alternative to reduce these side effects. AIM: In this trial, we aimed to
      evaluate the effect of lidocaine in preventing tracheal intubation related side
      effects at emergence from anaesthesia, when instilled onto the glottis before
      intubation or used to inflate the endotracheal tube cuff. METHODS: Eighty
      patients scheduled to elective surgery of less than 120 minutes under general
      anaesthesia were enrolled in this prospective, randomized, controlled, double
      blind study. As they receive instillation of 2% lidocaine or saline onto the
      glottis before intubation, and as they have their endotracheal tube cuff filled
      with 2% lidocaine or saline, the patients were randomized in four groups. S-S
      (Saline instillation and saline in the cuff); S-Lido (saline instillation and
      lidocaine in the cuff); Lido-S (lidocaine instillation and saline in the cuff);
      Lido-Lido (lidocaine instillation and lidocaine in the cuff). The primary outcome
      was the incidence of coughing before extubation. The secondary outcomes were sore
      throat scores at H1 and H24 postoperatively and incidence of dysphagia, dysphonia
      and laryngeal dyspnea during the first 24 hours. RESULTS: Coughing occurred in
      80%, 70%, 30% and 20% of patients in S-S, S-Lido, Lido-S and Lido-Lido groups
      respectively. When compared to S-S group, the incidence of coughing was
      significantly reduced in Lido-S and Lido-Lido groups but not in S-Lido group
      (p1=0.003; p2=0.0003; p3=0.7 respectively). Sore throat scores at H1 and H24 were
      significantly lower in Lido-S and Lido-Lido groups (p1=0.00002 and p2=0.01).
      There was no significant difference between groups regarding the incidence of
      dysphagia, dysphonia and laryngeal dyspnea. CONCLUSION: When instilled onto the
      glottis before intubation, lidocaine reduced both the incidence of coughing and
      the severity of postoperative sore throat in surgery of less than 120 minutes.
      Intracuff lidocaine was not effective to reduce neither coughing nor sore throat
      severity.

PMID- 24879168
TI  - A cannonball through the chest: disseminated tuberculosis, threatening the aortic
      arch.
AB  - BACKGROUND: In 2012 the World Health Organization reported 8.7 million new cases
      of Tuberculosis worldwide, causing 1.4 million deaths (1). Despite modern drug
      therapy, this disease continues to present in novel ways and mimic other diseases
      causing misdiagnosis. AIM: We report this case to educate on the reason to
      suspect atypical Tuberculosis presentation, even if a common disease is
      diagnosed, when Tuberculosis remains in the differential. We also demonstrate
      that with globalization and patient moving between countries, that these
      presentations can occur in locations, where such atypical manifestations are very
      uncommon. CASE: We report on a 48 year old man with one month of malaise, fever,
      productive cough, night sweats, chills, pleuritic chest pain, weight loss and
      progressive non-painful swelling on his thorax. Initial diagnoses of interstitial
      pneumonia and a thoracic subcutaneous abscess were made. Needle drainage was
      attempted, with thick purulent material returned. When the sternum was not struck
      with the needle, a thoracic computed tomography scan was performed. A milliary
      pattern was noted in the lungs, with a large abscess present anteriorly,
      completely obliterating the manubrium, approaching the aorta with distant
      lesions. Subsequent analysis showed the material to be pan-sensitive M.
      Tuberculosis. CONCLUSION: The issue that this case raises is that when
      tuberculosi is in the differential, even common diseases may in fact be atypical
      manifestations of tuberculosis. In addition, when a shallow surgical procedure is
      going to be performed on the thoracic soft tissues, particularly when
      tuberculosis is suspected, imaging of the thorax should be obtained.

PMID- 24879169
TI  - [Thrombosis in Celiac disease: clinical characteristics and role of thrombophilic
      factors: a retrospective study of 4 cases].

PMID- 24879170
TI  - Spontaneous testicular infarction mimicking testicular neoplasm.

PMID- 24879171
TI  - [Candida tropicalis endocarditis on native valve: a new observation].

PMID- 24879172
TI  - [Behcet's refractory uveitis treated successfully by infliximab].

PMID- 24879173
TI  - Severe autoimmune hemolytic anemia in a patient with chronic hepatitis C during
      treatment with Peg interferon alfa-2a and ribavirin.

PMID- 24879273
TI  - [Obesity, or fat metonymy].

PMID- 24879274
TI  - [Metabolic pro-inflammatory stress, adipokines and respiratory diseases].

PMID- 24879275
TI  - [Lung function tests in obese patients].

PMID- 24879276
TI  - [Pulmonologist attitude and counseling towards obese patient].

PMID- 24879277
TI  - [Pathophysiological features of COPD in obese patients].

PMID- 24879278
TI  - [Implementation of pulmonary rehabilitation for COPD].

PMID- 24879279
TI  - [Asthma in obese: a peculiar phenotype].

PMID- 24879280
TI  - [Bronchial epithelium role in asthma pathogenesis].

PMID- 24879281
TI  - [Small airways involvement in asthma].

PMID- 24879282
TI  - [Respiratory disorders and childhood obesity].

PMID- 24879283
TI  - [From Pickwick syndrome to obesity hypoventilation syndrome].

PMID- 24879284
TI  - [Are there other treatments than CPAP?].

PMID- 24879285
TI  - [Lymph node tuberculosis management].

PMID- 24879286
TI  - [Neo-adjuvant chemotherapy contribution in bronchopulmonary non small cell
      cancers: surgeon opinion].

PMID- 24879287
TI  - Lung cancer up to date.

PMID- 24879288
TI  - Relationship between hospital volume and hemorrhagic complication after
      percutaneous renal biopsy: results from the Japanese diagnosis procedure
      combination database.
AB  - BACKGROUND: Although hemorrhagic complications are major complications of
      percutaneous renal biopsy (PRB), the relationship between procedure volume and
      morbidity remains unclear for PRB. The present study investigated the impact of
      hospital volume on the occurrence of hemorrhagic complications after PRB.
      METHODS: Using large claims-based data in the diagnosis procedure combination
      database in Japan, we identified inpatients with renal disorders who underwent
      PRB within 4 days after admission during July to December 2007 to 2010. We
      assessed patient age, sex, clinical syndromes, hemorrhagic complications and
      diagnoses, and annual hospital volume of PRB divided into quintiles. Multivariate
      logistic regression analyses fitted with a generalized estimation equation were
      performed accounting for within-hospital clustering. RESULTS: A total of 15,191
      patients were identified from 942 hospitals. The overall proportion of
      hemorrhagic complications was 2.1 %, including diagnoses of hemorrhagic events
      (1.6 %), red blood cell transfusion (0.5 %), and requiring angiography or
      endovascular procedure (0.1 %). In-hospital deaths attributable to the
      complications occurred in 0.06 % of the patients. Patients with rapidly
      progressive nephritic syndrome (odds ratio 3.41, 95 % confidence interval 2.22
      5.25) had significantly higher incidence than those with chronic nephritic
      syndrome. No significant association was observed between hospital volume and
      hemorrhagic complications, with odds ratios for the low-intermediate,
      intermediate, intermediate-high, and high-volume groups relative to the low
      volume group of 0.74 (0.43-1.26), 1.19 (0.74-1.92), 1.16 (0.67-2.00), and 1.35
      (0.78-2.34), respectively. CONCLUSIONS: No significant relationship was observed
      between hemorrhagic complication incidence and hospital volume regarding PRB.

PMID- 24879289
TI  - Discovery of triterpenoids as reversible inhibitors of alpha/beta-hydrolase
      domain containing 12 (ABHD12).
AB  - BACKGROUND: alpha/beta-Hydrolase domain containing (ABHD)12 is a recently
      discovered serine hydrolase that acts in vivo as a lysophospholipase for
      lysophosphatidylserine. Dysfunctional ABHD12 has been linked to the rare
      neurodegenerative disorder called PHARC (polyneuropathy, hearing loss, ataxia,
      retinosis pigmentosa, cataract). In vitro, ABHD12 has been implicated in the
      metabolism of the endocannabinoid 2-arachidonoylglycerol (2-AG). Further studies
      on ABHD12 function are hampered as no selective inhibitor have been identified to
      date. In contrast to the situation with the other endocannabinoid hydrolases,
      ABHD12 has remained a challenging target for inhibitor development as no crystal
      structures are available to facilitate drug design. METHODOLOGY/PRINCIPAL
      FINDINGS: Here we report the unexpected discovery that certain triterpene-based
      structures inhibit human ABHD12 hydrolase activity in a reversible manner, the
      best compounds showing submicromolar potency. Based on structure activity
      relationship (SAR) data collected for 68 natural and synthetic triterpenoid
      structures, a pharmacophore model has been constructed. A pentacyclic triterpene
      backbone with carboxyl group at position 17, small hydrophobic substituent at the
      position 4, hydrogen bond donor or acceptor at position 3 accompanied with four
      axial methyl substituents was found crucial for ABHD12 inhibitor activity.
      Although the triterpenoids typically may have multiple protein targets, we
      witnessed unprecedented selectivity for ABHD12 among the metabolic serine
      hydrolases, as activity-based protein profiling of mouse brain membrane proteome
      indicated that the representative ABHD12 inhibitors did not inhibit other serine
      hydrolases, nor did they target cannabinoid receptors. CONCLUSIONS/SIGNIFICANCE:
      We have identified reversibly-acting triterpene-based inhibitors that show
      remarkable selectivity for ABHD12 over other metabolic serine hydrolases. Based
      on SAR data, we have constructed the first pharmacophore model of ABHD12
      inhibitors. This model should pave the way for further discovery of novel lead
      structures for ABHD12 selective inhibitors.

PMID- 24879290
TI  - Cimetidine attenuates vinorelbine-induced phlebitis in mice by militating E
      selectin expression.
AB  - PURPOSE: We investigated E-selectin expression in mice and rabbits with
      vinorelbine-induced phlebitis and the effect of cimetidine. To find the
      relationship between E-selectin expression and vinorelbine-induced phlebitis.
      METHODS: Mouse and rabbit model of vinorelbine-induced phlebitis was established
      by intravenous infusion of vinorelbine. Pathological observation, molecular
      biological determination of E-selectin and protein function of it was evaluated.
      RESULTS: Grossly, we observed swelling, edema and cord-like vessel changes in
      mice receiving vinorelbine but only mild edema in mice pretreated with
      cimetidine. Pathological scoring yielded a total score of 37 for vinorelbine
      treated mice and 17 for mice pretreated with cimetidine (P < 0.05). ELISA
      revealed that rabbits treated with vinorelbine had markedly higher serum contents
      of E-selectin than normal saline (NS) controls (vinorelbine 1.534 +/- 0.449 vs.
      NS 0.746 +/- 0.170 ng/mL, P < 0.05), which was markedly attenuated by cimetidine
      (cimetidine 0.717 +/- 0.468 vs. vinorelbine 1.534 +/- 0.449 ng/mL, P < 0.05).
      Rose Bengal staining assays showed that vinorelbine markedly increased the
      adhesion rate of neutrophils for endothelial cells (vinorelbine 38.70 +/- 8.34%
      vs. controls 8.93 +/- 4.85%, P < 0.01), which, however, was significantly
      suppressed by cimetidine (9.93 +/- 5.91%, P < 0.01 vs. vinorelbine). In E
      selectin knockout mice, we found no apparent difference in tail swelling in mice
      receiving vinorelbine or cimetidine and vinorelbine. CONCLUSIONS: In conclusion,
      cimetidine attenuates vinorelbine-induced phlebitis in mice probably by
      suppressing increased expression of E-selectin.

PMID- 24879291
TI  - Studying the morphology of lyophilized protein solids using X-ray micro-CT:
      effect of post-freeze annealing and controlled nucleation.
AB  - The objective of this study was to determine how different techniques used during
      the freezing step of lyophilization affect morphology of the dried protein
      solids. Aqueous solutions containing recombinant human albumin, trehalose, and
      sodium phosphate buffer were dried after their freezing by shelf-ramp cooling,
      immersion in liquid nitrogen, or controlled ice nucleation. Some shelf-frozen
      solutions were heat treated (annealed) before the vacuum drying. We used three
      dimensional (3D) X-ray micro-computed tomography (micro-CT) and scanning electron
      microscopy (SEM) to study the morphology of solids. The X-ray micro-CT images of
      the lyophilized microporous solids showed traces of varied size and structure ice
      crystals that were comparable to corresponding SEM images. A post-freeze heat
      treatment and a controlled nucleation both induced larger ice crystal ghosts in
      the solids. The variations in the structure of walls surrounding ice crystals,
      formed by the different freezing procedures, should affect the water vapor
      transition during the primary and secondary drying. Some solids also showed
      higher-density layer in the upper surface. Overall, the simple sample preparation
      procedures and the ample morphological information make the X-ray micro-CT
      appropriate for analyzing lyophilized pharmaceuticals. 

PMID- 24879292
TI  - A 5,7-dimethoxyflavone/hydroxypropyl-beta-cyclodextrin inclusion complex with
      anti-butyrylcholinesterase activity.
AB  - This study aimed to improve the water solubility of 5,7-dimethoxyflavone (5,7
      DMF) isolated from Kaempferia parviflora by complexation with 2-hydroxypropyl
      beta-cyclodextrin (HPbeta-CD). The phase solubility profile of 5,7-DMF in the
      presence of HPbeta-CD was classified as AL-type and indicated a 1:1 mole ratio.
      Differential scanning colorimetry, X-ray diffraction, NMR and SEM analyses
      supported the formation of a 5,7-DMF/HPbeta-CD inclusion complex involving the A
      ring of 5,7-DMF inside the HPbeta-CD cavity. This is the first example of CD
      inclusion with the A ring of non-hydroxyl flavones. The stability and binding
      constants of the complexes were determined using the phase solubility and UV-vis
      absorption spectroscopy, respectively. The water solubility of 5,7-DMF was
      increased 361.8-fold by complexation with HPbeta-CD and overcame the
      precipitation problem observed in aqueous buffers, such as during in vitro anti
      butyrylcholinesterase activity assays. The 1:1 mole ratio of the 5,7-DMF/HPbeta
      CD complex showed a 2.7-fold higher butyrylcholinesterase inhibitory activity (in
      terms of the IC50 value) compared to the non-complexed compound. 

PMID- 24879293
TI  - Interferon regulatory factor 3 in adaptive immune responses.
AB  - Interferon regulatory factor (IRF) 3 plays a key role in innate responses against
      viruses. Indeed, activation of this transcription factor triggers the expression
      of type I interferons and downstream interferon-stimulated genes in infected
      cells. Recent evidences indicate that this pathway also modulates adaptive immune
      responses. This review focuses on the different mechanisms that are implicated in
      this process. We discuss the role of IRF3 within antigen-presenting cells and T
      lymphocytes in the polarization of the cellular immune response and its
      implication in the pathogenesis of immune disorders. 

PMID- 24879296
TI  - Plant evolution at the interface of paleontology and developmental biology: An
      organism-centered paradigm.
AB  - Paleontology yields essential evidence for inferring not only the pattern of
      evolution, but also the genetic basis of evolution within an ontogenetic
      framework. Plant fossils provide evidence for the pattern of plant evolution in
      the form of transformational series of structure through time. Developmentally
      diagnostic structural features that serve as "fingerprints" of regulatory genetic
      pathways also are preserved by plant fossils, and here we provide examples of how
      those fingerprints can be used to infer the mechanisms by which plant form and
      development have evolved. When coupled with an understanding of variations and
      systematic distributions of specific regulatory genetic pathways, this approach
      provides an avenue for testing evolutionary hypotheses at the organismal level
      that is analogous to employing bioinformatics to explore genetics at the genomic
      level. The positions where specific genes, gene families, and developmental
      regulatory mechanisms first appear in phylogenies are correlated with the
      positions where fossils with the corresponding structures occur on the tree,
      thereby yielding testable hypotheses that extend our understanding of the role of
      developmental changes in the evolution of the body plans of vascular plant
      sporophytes. As a result, we now have new and powerful methodologies for
      characterizing major evolutionary changes in morphology, anatomy, and physiology
      that have resulted from combinations of genetic regulatory changes and that have
      produced the synapomorphies by which we recognize major clades of plants.

PMID- 24879294
TI  - Cyclin A2, a novel regulator of EMT.
AB  - Our previous work showed that Cyclin A2 deficiency promotes cell invasion in
      fibroblasts. Given that the majority of cancers emerge from epithelia, we
      explored novel functions for Cyclin A2 by depleting it in normal mammary
      epithelial cells. This caused an epithelial to mesenchymal transition (EMT)
      associated with loss of cell-to-cell contacts, decreased E-Cadherin expression
      and increased invasive properties characterized by a reciprocal regulation of
      RhoA and RhoC activities, where RhoA-decreased activity drove cell invasiveness
      and E-Cadherin delocalization, and RhoC-increased activity only supported cell
      motility. Phenotypes induced by Cyclin A2 deficiency were exacerbated upon
      oncogenic activated-Ras expression, which led to an increased expression of EMT
      related transcriptional factors. Moreover, Cyclin A2-depleted cells exhibited
      stem cell-like properties and increased invasion in an in vivo avian embryo
      model. Our work supports a model where Cyclin A2 downregulation facilitates
      cancer cell EMT and metastatic dissemination.

PMID- 24879297
TI  - Complications following liver transplantation for progressive familial
      intrahepatic cholestasis.

PMID- 24879295
TI  - Hepatitis C NS5A protein: two drug targets within the same protein with different
      mechanisms of resistance.
AB  - The era of interferon-free antiviral treatments for hepatitis C virus infection
      has arrived. With increasing numbers of approved antivirals, evaluating all
      parameters that may influence response is necessary to choose optimal
      combinations for treatment success. Targeting NS5A has become integral in
      antiviral combinations in clinical development. Daclatasvir and ledipasvir belong
      to the NS5A inhibitor class, which directly target the NS5A protein. Alisporivir,
      a host-targeting antiviral, is a cyclophilin inhibitor that indirectly targets
      NS5A by blocking NS5A/cyclophilin A interaction. Resistance to daclatasvir and
      ledipasvir differs from alisporivir, with mutations arising in NS5A domains I and
      II, respectively. Combining these two classes acting on distinct NS5A domains
      represents an attractive strategy for potentially effective interferon-free
      treatments for chronic hepatitis C infection. 

PMID- 24879299
TI  - Significant perturbation in renal functional magnetic resonance imaging
      parameters and contrast retention for iodixanol compared with iopromide: an
      experimental study using blood-oxygen-level-dependent/diffusion-weighted magnetic
      resonance imaging and computed tomography in rats.
AB  - OBJECTIVES: The objective of this study was to investigate the renal changes
      after intravenous administration of a high dose of either iodixanol or iopromide
      using functional magnetic resonance imaging (MRI) and computed tomography (CT).
      MATERIALS AND METHODS: The study was approved by the institutional committee on
      animal research. Seventy-two male Sprague-Dawley rats were divided into 5
      cohorts, comprising normal saline (NS), iopromide, iopromide + NS, iodixanol, and
      iodixanol + NS. Intravenous contrast was administrated at 8 g iodine/kg of body
      weight. Renal CT, quantitative functional MRI of blood-oxygen-level-dependent
      (BOLD) imaging and diffusion-weighted imaging (DWI), and histologic examinations
      were performed for 18 days after contrast administration. Statistical analysis
      was performed by using 1-way analysis of variance, Mann-Whitney test, and
      regression analysis. RESULTS: In the renal cortex, BOLD showed persistent
      elevation of R2* and DWI showed persistent suppression of apparent diffusion
      coefficient after iodixanol administration for 18 days. Compared with iopromide,
      adjusted DeltaR2* (DeltaR2*adj) was significantly higher in the iodixanol group
      from 1 hour to 18 days (P < 0.04) after contrast; adjusted DeltaADC (DeltaADCadj)
      was significantly more pronounced at day 6 (P = 0.01) after contrast. The
      iodixanol cohort also exhibited persistently higher attenuation in the renal
      cortex on CT and more severe microscopic renal cortical vacuolization up to 18
      days. Intravenous hydration decreased the magnetic resonance changes in both
      groups but more markedly with iodixanol. CONCLUSIONS: At high doses, iodixanol
      induced greater changes in renal functional MRI (BOLD and DWI) relative to
      iopromide. Combined with longer contrast retention within the kidney, this
      suggests that iodixanol may produce more severe and longer-lasting contrast
      induced renal damage.

PMID- 24879298
TI  - Quantitative high-resolution renal perfusion imaging using 3-dimensional through
      time radial generalized autocalibrating partially parallel acquisition.
AB  - OBJECTIVES: Dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI)
      examinations of the kidneys provide quantitative information on renal perfusion
      and filtration. However, these examinations are often difficult to implement
      because of respiratory motion and their need for a high spatiotemporal resolution
      and 3-dimensional coverage. Here, we present a free-breathing quantitative renal
      DCE-MRI examination acquired with a highly accelerated stack-of-stars trajectory
      and reconstructed with 3-dimensional (3D) through-time radial generalized
      autocalibrating partially parallel acquisition (GRAPPA), using half and quarter
      doses of gadolinium contrast. MATERIALS AND METHODS: Data were acquired in 10
      asymptomatic volunteers using a stack-of-stars trajectory that was undersampled
      in-plane by a factor of 12.6 with respect to Nyquist sampling criterion and using
      partial Fourier of 6/8 in the partition direction. Data had a high temporal (2.1
      2.9 seconds per frame) and spatial (approximately 2.2 mm) resolution with full 3D
      coverage of both kidneys (350-370 mm * 79-92 mm). Images were successfully
      reconstructed with 3D through-time radial GRAPPA, and interframe respiratory
      motion was compensated by using an algorithm developed to automatically use
      images from multiple points of enhancement as references for registration.
      Quantitative pharmacokinetic analysis was performed using a separable dual
      compartment model. RESULTS: Region-of-interest (ROI) pharmacokinetic analysis
      provided estimates (mean (SD)) of quantitative renal parameters after a half
      dose: 218.1 (57.1) mL/min per 100 mL; plasma mean transit time, 4.8 (2.2)
      seconds; renal filtration, 28.7 (10.0) mL/min per 100 mL; and tubular mean
      transit time, 131.1 (60.2) seconds in 10 kidneys. The ROI pharmacokinetic
      analysis provided estimates (mean (SD)) of quantitative renal parameters after a
      quarter dose: 218.1 (57.1) mL/min per 100 mL; plasma mean transit time, 4.8 (2.2)
      seconds; renal filtration, 28.7 (10.0) mL/min per 100 mL; and tubular mean
      transit time, 131.1 (60.2) seconds in the 10 kidneys. Three-dimensional pixelwise
      parameter maps were also evaluated. CONCLUSIONS: Highly undersampled data were
      successfully reconstructed with 3D through-time radial GRAPPA to achieve a high
      resolution 3-dimensional renal DCE-MRI examination. The acquisition was
      completely free breathing, and the images were registered to compensate for
      respiratory motion. This allowed for an accurate high-resolution 3D quantitative
      renal functional mapping of perfusion and filtration parameters.

PMID- 24879300
TI  - r TPPM: towards improving solid-state NMR two-pulse phase-modulation
      heteronuclear dipolar decoupling sequence by refocusing.
AB  - We present here a simple refocused modification, r TPPM, of the Two-Pulse Phase
      Modulation (TPPM) heteronuclear decoupling method, which improves decoupling and
      makes the sequence much more robust with respect to essential experimental
      parameters. The modified sequence is compared with the established TPPM sequence
      and a variety of other decoupling sequences at low to moderate magic-angle
      spinning frequencies. Simulations are shown to compare TPPM and r TPPM with
      respect to various experimental parameters. The observations from simulations are
      corroborated with experimental findings at two spinning frequencies on U-(13)C
      glycine and U-(13)C-L-histidine.HCl.H2O. 

PMID- 24879301
TI  - A tumour mRNA-triggered nanocarrier for multimodal cancer cell imaging and
      therapy.
AB  - We have established a tumour marker activated nanocarrier that can respond to the
      intracellular mRNA, allowing multimodal cancer cell imaging and therapy. 

PMID- 24879302
TI  - Exchange-biased hybrid ferromagnetic-multiferroic core-shell nanostructures.
AB  - Artificial exchange-biased two-phase core-shell nanostructures consisting of
      ferromagnetic (Ni) and multiferroic (BiFeO3) materials were manufactured by a two
      step method. An exchange bias effect was observed and studied, which indicates
      that it is possible to fabricate ferromagnetic-multiferroic nanostructures to
      utilize the combined ferroelectric and antiferromagnetic functionalities of
      bismuth ferrite. 

PMID- 24879303
TI  - Recognition memory for colored and black-and-white scenes in normal and color
      deficient observers (dichromats).
AB  - Color deficient (dichromat) and normal observers' recognition memory for colored
      and black-and-white natural scenes was evaluated through several parameters: the
      rate of recognition, discrimination (A'), response bias (B"D), response
      confidence, and the proportion of conscious recollections (Remember responses)
      among hits. At the encoding phase, 36 images of natural scenes were each
      presented for 1 sec. Half of the images were shown in color and half in black-and
      white. At the recognition phase, these 36 pictures were intermixed with 36 new
      images. The participants' task was to indicate whether an image had been
      presented or not at the encoding phase, to rate their level of confidence in his
      her/his response, and in the case of a positive response, to classify the
      response as a Remember, a Know or a Guess response. Results indicated that
      accuracy, response discrimination, response bias and confidence ratings were
      higher for colored than for black-and-white images; this advantage for colored
      images was similar in both groups of participants. Rates of Remember responses
      were not higher for colored images than for black-and-white ones, whatever the
      group. However, interestingly, Remember responses were significantly more often
      based on color information for colored than for black-and-white images in normal
      observers only, not in dichromats. 

PMID- 24879304
TI  - Comparison of consumption patterns, biomarkers of exposure, and subjective
      effects in cigarette smokers who switched to dissolvable tobacco (Camel Orbs),
      dual use, or tobacco abstinence.
AB  - INTRODUCTION: The objectives of this trial were to investigate short-term changes
      in product usage, tobacco-related biomarkers of exposure, and subjective effects
      in smokers who switched to dissolvable tobacco (Camel Orbs) use. METHODS:
      Participants were randomized into 1 of 4 groups (continued smoking, switched to
      consuming Orbs, switched to dual use of cigarettes and Orbs, and tobacco
      abstinent) and confined for 6 days with dietary restrictions. Most measurements
      were at baseline and days 1, 3, and 5 of intervention. Mouth-level tar and
      nicotine exposures were estimated by filter tip analysis. Twenty biomarkers were
      quantified in 24-hr urine; 4 were quantified in blood/plasma (carboxyhemoglobin,
      nicotine, cotinine, and thiocyanate). Ratings for nicotine dependence and
      withdrawal symptoms were scored. RESULTS: After 5 days, substantial and
      statistically significant reductions (~30%-90%) in all biomarkers were observed
      in the Orbs and abstinent groups compared to baseline. Numerous smaller
      reductions (~7%-30%) were also noted in the continued smoking and dual-use groups
      (generally similar in magnitude for both groups). Subjective questionnaire
      findings indicated greater withdrawal discomfort levels throughout the
      intervention period for the nonsmoking groups. For subjects that continued
      smoking, clinical confinement conditions did not significantly alter product use
      behavior and toxicant exposure profile compared to baseline. CONCLUSIONS:
      Substantial reductions in toxicant exposure occurred for participants that did
      not smoke. Cigarette smokers that switched to Orbs use showed reductions in all
      biomarkers, similar to abstinent group. Changes in toxicant exposure for the dual
      use group were similar to the continued-smoking group, consistent with minimal
      changes observed in that group's product use behavior (small reduction in
      cigarettes per day and small increase in Orbs use).

PMID- 24879305
TI  - The Index-based Subgraph Matching Algorithm with General Symmetries (ISMAGS):
      exploiting symmetry for faster subgraph enumeration.
AB  - Subgraph matching algorithms are used to find and enumerate specific
      interconnection structures in networks. By enumerating these specific
      structures/subgraphs, the fundamental properties of the network can be derived.
      More specifically in biological networks, subgraph matching algorithms are used
      to discover network motifs, specific patterns occurring more often than expected
      by chance. Finding these network motifs yields information on the underlying
      biological relations modelled by the network. In this work, we present the Index
      based Subgraph Matching Algorithm with General Symmetries (ISMAGS), an improved
      version of the Index-based Subgraph Matching Algorithm (ISMA). ISMA quickly finds
      all instances of a predefined motif in a network by intelligently exploring the
      search space and taking into account easily identifiable symmetric structures.
      However, more complex symmetries (possibly involving switching multiple nodes)
      are not taken into account, resulting in superfluous output. ISMAGS overcomes
      this problem by using a customised symmetry analysis phase to detect all
      symmetric structures in the network motif subgraphs. These structures are then
      converted to symmetry-breaking constraints used to prune the search space and
      speed up calculations. The performance of the algorithm was tested on several
      types of networks (biological, social and computer networks) for various
      subgraphs with a varying degree of symmetry. For subgraphs with complex (multi
      node) symmetric structures, high speed-up factors are obtained as the search
      space is pruned by the symmetry-breaking constraints. For subgraphs with no or
      simple symmetric structures, ISMAGS still reduces computation times by optimising
      set operations. Moreover, the calculated list of subgraph instances is minimal as
      it contains no instances that differ by only a subgraph symmetry. An
      implementation of the algorithm is freely available at
      https://github.com/mhoubraken/ISMAGS. 

PMID- 24879306
TI  - Identification of different varieties of sesame oil using near-infrared
      hyperspectral imaging and chemometrics algorithms.
AB  - This study investigated the feasibility of using near infrared hyperspectral
      imaging (NIR-HSI) technique for non-destructive identification of sesame oil.
      Hyperspectral images of four varieties of sesame oil were obtained in the
      spectral region of 874-1734 nm. Reflectance values were extracted from each
      region of interest (ROI) of each sample. Competitive adaptive reweighted sampling
      (CARS), successive projections algorithm (SPA) and x-loading weights (x-LW) were
      carried out to identify the most significant wavelengths. Based on the sixty
      four, seven and five wavelengths suggested by CARS, SPA and x-LW, respectively,
      two classified models (least squares-support vector machine, LS-SVM and linear
      discriminant analysis,LDA) were established. Among the established models, CARS
      LS-SVM and CARS-LDA models performed well with the highest classification rate
      (100%) in both calibration and prediction sets. SPA-LS-SVM and SPA-LDA models
      obtained better results (95.59% and 98.53% of classification rate in prediction
      set) with only seven wavelengths (938, 1160, 1214, 1406, 1656, 1659 and 1663 nm).
      The x-LW-LS-SVM and x-LW-LDA models also obtained satisfactory results (>80% of
      classification rate in prediction set) with the only five wavelengths (921, 925,
      995, 1453 and 1663 nm). The results showed that NIR-HSI technique could be used
      to identify the varieties of sesame oil rapidly and non-destructively, and CARS,
      SPA and x-LW were effective wavelengths selection methods. 

PMID- 24879307
TI  - Pea p68, a DEAD-box helicase, provides salinity stress tolerance in transgenic
      tobacco by reducing oxidative stress and improving photosynthesis machinery.
AB  - BACKGROUND: The DEAD-box helicases are required mostly in all aspects of RNA and
      DNA metabolism and they play a significant role in various abiotic stresses,
      including salinity. The p68 is an important member of the DEAD-box proteins
      family and, in animal system, it is involved in RNA metabolism including pre-RNA
      processing and splicing. In plant system, it has not been well characterized.
      Here we report the cloning and characterization of p68 from pea (Pisum sativum)
      and its novel function in salinity stress tolerance in plant. RESULTS: The pea
      p68 protein self-interacts and is localized in the cytosol as well as the
      surrounding of cell nucleus. The transcript of pea p68 is upregulated in response
      to high salinity stress in pea. Overexpression of p68 driven by constitutive
      cauliflower mosaic virus-35S promoter in tobacco transgenic plants confers
      enhanced tolerances to salinity stress by improving the growth, photosynthesis
      and antioxidant machinery. Under stress treatment, pea p68 overexpressing tobacco
      accumulated higher K+ and lower Na+ level than the wild-type plants. Reactive
      oxygen species (ROS) accumulation was remarkably regulated by the overexpression
      of pea p68 under salinity stress conditions, as shown from TBARS content,
      electrolyte leakage, hydrogen peroxide accumulation and 8-OHdG content and
      antioxidant enzyme activities. CONCLUSIONS: To the best of our knowledge this is
      the first direct report, which provides the novel function of pea p68 helicase in
      salinity stress tolerance. The results suggest that p68 can also be exploited for
      engineering abiotic stress tolerance in crop plants of economic importance.

PMID- 24879309
TI  - The CXCR4/CXCL12 axis in cutaneous malignancies with an emphasis on melanoma.
AB  - The highly metastatic and variable behavior of melanoma has accentuated the need
      for early detection and targeted therapy. Putative targets identified include
      those belonging to the extensive network of chemokines and their receptors. One
      such target is the chemokine receptor CXCR4, a G protein-coupled receptor with a
      34 amino acid extracellular N-terminus, the primary ligand of which is CXCL12
      (SDF-1, stromal derived factor-1). The ligand uniquely utilizes the N-terminus of
      CXCR4 for signal transduction and stimulates the protein kinase B (AKT)/mitogen
      activated protein kinase (MAPK) pathway. Functionally, the CXCR4/CXCL12 axis is
      believed to play a key role in cell migration and proliferation. Upregulation of
      CXCR4 and consequently dysregulation of the CXCR4/CXCL12 axis has been implicated
      in the progression of several lineage-unrelated malignancies including melanoma.
      The contributions of the CXCR4/CXCL12 axis in melanomagenesis are well
      documented. More recently, the potential cooperativity between the mutational
      status of BRAF and the CXCR4/CXCL12 axis has been shown, lending credence to the
      concept that both CXCR4 and CXCL12 may be putative targets for therapy in
      melanoma. In this review, we summarize the role of the CXCR4/CXCL12 axis in
      cancer progression and metastasis, with an emphasis on cutaneous malignancy,
      melanoma in particular. Furthermore, we discuss the effects of CXCL12 on CXCR4
      expressing malignant cells in vitro and the potential prognostic utility of both
      CXCR4 and CXCL12 expressions. Lastly, we highlight the therapeutic potential of
      targeting this axis and the unique response of CXCR4 expression to anti-cancer
      treatments with an emphasis on melanoma.

PMID- 24879310
TI  - Taking stock of four decades of quantitative research on stakeholder
      participation and evaluation use: a systematic map.
AB  - Stakeholder participation and evaluation use have attracted a lot of attention
      from practitioners, theorists and researchers. A common hypothesis is that
      participation is positively associated with evaluation use. Whereas the number of
      empirical studies conducted on this topic is impressive, quantitative research
      has held a minority position within this scientific production. This study
      mobilizes systematic review methods to 'map' the empirical literature that has
      quantitatively studied participation and use. The goal is to take stock and
      assess the strength of evidence of this literature (but not to synthesize the
      findings) and, based on this assessment, to provide directions for future
      research. 

PMID- 24879311
TI  - A pH-responsive drug nanovehicle constructed by reversible attachment of
      cholesterol to PEGylated poly(l-lysine) via catechol-boronic acid ester
      formation.
AB  - The present work reports the construction of a drug delivery nanovehicle via a pH
      sensitive assembly strategy for improved cellular internalization and
      intracellular drug liberation. Through spontaneous formation of boronate linkage
      in physiological conditions, phenylboronic acid-modified cholesterol was able to
      attach onto catechol-pending methoxypoly(ethylene glycol)-block-poly(l-lysine).
      This comb-type polymer can self-organize into a micellar nanoconstruction that is
      able to effectively encapsulate poorly water-soluble agents. The blank micelles
      exhibited negligible in vitro cytotoxicity, yet doxorubicin (DOX)-loaded micelles
      could effectively induce cell death at a level comparable to free DOX. Owing to
      the acid-labile feature of the boronate linkage, a reduction in environmental pH
      from pH 7.4 to 5.0 could trigger the dissociation of the nanoconstruction, which
      in turn could accelerate the liberation of entrapped drugs. Importantly, the
      blockage of endosomal acidification in HeLa cells by NH4Cl treatment
      significantly decreased the nuclear uptake efficiency and cell-killing effect
      mediated by the DOX-loaded nanoassembly, suggesting that acid-triggered
      destruction of the nanoconstruction is of significant importance in enhanced drug
      efficacy. Moreover, confocal fluorescence microscopy and flow cytometry assay
      revealed the effective internalization of the nanoassemblies, and their cellular
      uptake exhibited a cholesterol dose-dependent profile, indicating the
      contribution of introduced cholesterol functionality to the transmembrane process
      of the nanoassembly. 

PMID- 24879312
TI  - Bioceramics in ophthalmology.
AB  - The benefits of ceramics in biomedical applications have been universally
      appreciated as they exhibit an extraordinarily broad set of physico-chemical,
      mechanical and biological properties which can be properly tailored by acting on
      their composition, porosity and surface texture to increase their versatility and
      suitability for targeted healthcare applications. Bioceramics have traditionally
      been used for the repair of hard tissues, such as bone and teeth, mainly due to
      their suitable strength for load-bearing applications, wear resistance
      (especially alumina, zirconia and composites thereof) and, in some cases, bone
      bonding ability (calcium orthophosphates and bioactive glasses). Bioceramics have
      been also applied in other medical areas, like ophthalmic surgery; although their
      use in such a context has been scientifically documented since the late 1700s,
      the potential and importance of ceramic ocular implants still seem to be
      underestimated and an exhaustive, critical assessment is currently lacking in the
      relevant literature. The present review aims to fill this gap by giving a
      comprehensive picture of the ceramic-based materials and implants that are
      currently used in ophthalmology and pointing out the strengths and weaknesses of
      the existing devices. A prospect for future research is also provided,
      highlighting the potential of new, smart bioceramics able to carry specific added
      values which could have a significant impact on the treatment of ocular diseases.

PMID- 24879313
TI  - Modulated regeneration of acid-etched human tooth enamel by a functionalized
      dendrimer that is an analog of amelogenin.
AB  - In the bioinspired repair process of tooth enamel, it is important to
      simultaneously mimic the organic-matrix-induced biomineralization and increase
      the binding strength at the remineralization interface. In this work, a fourth
      generation polyamidoamine dendrimer (PAMAM) is modified by dimethyl phosphate to
      obtain phosphate-terminated dendrimer (PAMAM-PO3H2) since it has a similar
      dimensional scale and peripheral functionalities to that of amelogenin, which
      plays important role in the natural development process of enamel. Its phosphate
      group has stronger affinity for calcium ion than carboxyl group and can
      simultaneously provide strong hydroxyapatite (HA)-binding capability. The MTT
      assay demonstrates the low cytotoxicity of PAMAM-PO3H2. Adsorption tests indicate
      that PAMAM-PO3H2 can be tightly adsorbed on the human tooth enamel. Scanning
      electron microscopy and X-ray diffraction are used to analyze the
      remineralization process. After being incubated in artificial saliva for 3weeks,
      there is a newly generated HA layer of 11.23MUm thickness on the acid-etched
      tooth enamel treated by PAMAM-PO3H2, while the thickness for the carboxyl
      terminated one (PAMAM-COOH) is only 6.02MUm. PAMAM-PO3H2 can regulate the
      remineralization process to form ordered new crystals oriented along the Z-axis
      and produce an enamel prism-like structure that is similar to that of natural
      tooth enamel. The animal experiment also demonstrates that PAMAM-PO3H2 can induce
      significant HA regeneration in the oral cavity of rats. Thus PAMAM-PO3H2 shows
      great potential as a biomimetic restorative material for human tooth enamel. 

PMID- 24879308
TI  - RNA polymerase II transcription elongation and Pol II CTD Ser2 phosphorylation: A
      tail of two kinases.
AB  - The transition between initiation and productive elongation during RNA Polymerase
      II (Pol II) transcription is a well-appreciated point of regulation across many
      eukaryotes. Elongating Pol II is modified by phosphorylation of serine 2 (Ser2)
      on its carboxy terminal domain (CTD) by two kinases, Bur1/Ctk1 in yeast and
      Cdk9/Cdk12 in metazoans. Here, we discuss the roles and regulation of these
      kinases and their relationship to Pol II elongation control, and focus on recent
      data from work in C. elegans that point out gaps in our current understand of
      transcription elongation. 

PMID- 24879314
TI  - Pregnancy-induced hypertension and diabetes and the risk of cardiovascular
      disease, stroke, and diabetes hospitalization in the year following delivery.
AB  - Although pregnancy events predict the long-term risk of chronic disease, little
      is known about their short-term impact because of the rarity of clinical events.
      We examined hospital discharge diagnoses linked to birth certificate data in the
      year following delivery for 849,639 births during 1995-2004 in New York City, New
      York. Adjusted odds ratios characterized the relationship between pregnancy
      complications and subsequent hospitalization for cardiovascular disease, stroke,
      and diabetes. Gestational hypertension was related to heart failure (adjusted
      odds ratio = 2.6, 95% confidence interval: 1.5, 4.5). Preeclampsia was related to
      all of the outcomes considered except type 1 diabetes, with adjusted odds ratios
      ranging from 2.0 to 4.1. Gestational diabetes was strongly related to the risk of
      subsequent diabetes (for type 1 diabetes, adjusted odds ratio = 40.4, 95%
      confidence interval: 23.8, 68.5; for type 2 diabetes, adjusted odds ratio = 22.6,
      95% confidence interval: 16.9, 30.4) but to no other outcomes. The relationship
      of pregnancy complications to future chronic disease is apparent as early as the
      year following delivery. Moreover, elucidating short-term clinical outcomes
      offers the potential for etiological insights into the relationship between
      pregnancy events and chronic disease over the life course. 

PMID- 24879315
TI  - Genetic associations with micronutrient levels identified in immune and
      gastrointestinal networks.
AB  - The discovery of vitamins and clarification of their role in preventing frank
      essential nutrient deficiencies occurred in the early 1900s. Much vitamin
      research has understandably focused on public health and the effects of single
      nutrients to alleviate acute conditions. The physiological processes for
      maintaining health, however, are complex systems that depend upon interactions
      between multiple nutrients, environmental factors, and genetic makeup. To analyze
      the relationship between these factors and nutritional health, data were obtained
      from an observational, community-based participatory research program of children
      and teens (age 6-14) enrolled in a summer day camp in the Delta region of
      Arkansas. Assessments of erythrocyte S-adenosylmethionine (SAM) and S
      adenosylhomocysteine (SAH), plasma homocysteine (Hcy) and 6 organic
      micronutrients (retinol, 25-hydroxy vitamin D3, pyridoxal, thiamin, riboflavin,
      and vitamin E), and 1,129 plasma proteins were performed at 3 time points in each
      of 2 years. Genetic makeup was analyzed with 1 M SNP genotyping arrays, and
      nutrient status was assessed with 24-h dietary intake questionnaires. A pattern
      of metabolites (met_PC1) that included the ratio of erythrocyte SAM/SAH, Hcy, and
      5 vitamins were identified by principal component analysis. Met_PC1 levels were
      significantly associated with (1) single-nucleotide polymorphisms, (2) levels of
      plasma proteins, and (3) multilocus genotypes coding for gastrointestinal and
      immune functions, as identified in a global network of metabolic/protein-protein
      interactions. Subsequent mining of data from curated pathway, network, and genome
      wide association studies identified genetic and functional relationships that may
      be explained by gene-nutrient interactions. The systems nutrition strategy
      described here has thus associated a multivariate metabolite pattern in blood
      with genes involved in immune and gastrointestinal functions. 

PMID- 24879316
TI  - Different associations of apoE gene polymorphism with metabolic syndrome in the
      Vojvodina Province (Serbia).
AB  - The metabolic syndrome (MetS) is a polygenic multifactorial metabolic disorder
      with strong socioeconomic influence. MetS has became a worldwide epidemic, that
      directly increases the risk of cardiovascular diseases and type 2 diabetes
      mellitus. The human apoE gene, coding Apolipoprotein E, has three common
      polymorphisms in human population: e2, e3 and e4, which are proved to be
      associated with impaired lipid metabolism. The contribution of apoE polymorphism
      to MetS disorders has not been investigated previously in Vojvodina Province,
      region with the highest number of obese people in Serbia. The aim of this study
      was to evaluate apoE gene polymorphism in relation to MetS disorders. The healthy
      control group of 30 individuals and 63 MetS patients were examined for apoE
      variants in relation to biochemical and anthropometric parameters. The genotypes
      were determined by PCR-RFLP. Regarding all parameters, significantly higher
      values were detected in MetS group compared to control. The MetS group of
      patients had significantly higher frequency of e4 allele. In addition, positive
      relation was revealed between e4 allele presence and all measured parameters. It
      was found that the e4 allele was related with a significantly increased OR of
      MetS disorders according to the International Diabetes Federation definition.
      These results suggested that e4 allele may act as a one of determinants for
      development of metabolic syndrome. 

PMID- 24879317
TI  - Chronic low-level arsenic exposure reduces lung function in male population
      without skin lesions.
AB  - OBJECTIVES: The respiratory effects of chronic low-level arsenic exposure from
      groundwater have been investigated in West Bengal, India. METHODS: The
      participants (834 non-smoking adult males) were subdivided in two groups: an
      arsenic-exposed group (n = 446, mean age 35.3 years) drinking arsenic
      contaminated groundwater (11-50 MUg/L) and a control group of 388 age-matched men
      drinking water containing <10 MUg/L of arsenic. Arsenic in water samples was
      measured by atomic absorption spectroscopy. The prevalence of respiratory
      symptoms was documented by structured, validated questionnaire. Pulmonary
      function test (PFT) was assessed by portable spirometer. RESULTS: Compared with
      control, the arsenic-exposed subjects had higher prevalence of upper and lower
      respiratory symptoms, dyspnea, asthma, eye irritation and headache. Besides,
      20.6% of arsenic-exposed subjects had lung function deficits (predominantly
      restrictive and combined types) compared with 13.6% of control (p < 0.05). A
      positive association was observed between arsenic concentration in drinking water
      and the prevalence of respiratory symptoms, while a negative association existed
      between arsenic level and spirometric parameters. CONCLUSIONS: The findings
      suggest that even low-level arsenic exposure has deleterious respiratory effects.

PMID- 24879319
TI  - The influence of a fibrous carbon envelope on the formation of CoFe nanoparticles
      for durable electrocatalytic oxygen evolution.
AB  - Co oxides are known to be active and stable alternative anode electrocatalysts
      possessing the potential to replace the best performing but most expensive Ir and
      Ru oxides in alkaline water electrolysis. Of late, Co oxides loaded on various
      carbon supports have been reported as a way to outperform Ir or Ru catalysts by
      improving the utilization efficiency. In this study, we introduce Co and Fe
      nanoparticles embedded carbon nanofibers (CoFe-CNFs), fabricated through
      electrospinning and pyrolysis of a polymer mixed with Co and Fe precursors. This
      method is a facile route for simultaneously making Co and Fe nanoparticles as
      well as the stable accommodation of the CoFe nanoparticles in the carbon support.
      We demonstrate the potential of the CoFe-CNFs as active and stable
      electrocatalysts for the oxygen evolution reaction (OER) in alkaline media. We
      conducted detailed physico-chemical characterizations to elucidate the effect of
      the CNFs on the OER activity and stability of the CoFe-CNFs. It is suggested that
      the CNFs are a medium in which OER-active CoFe alloy nanoparticles are formed
      homogeneously, and that carbon layers surrounding the nanoparticles are
      beneficial to the stability of the CoFe-CNFs in the OER. 

PMID- 24879318
TI  - Priority setting for the prevention and control of cardiovascular diseases: multi
      criteria decision analysis in four eastern Mediterranean countries.
AB  - OBJECTIVES: To explore the feasibility of using a simple multi-criteria decision
      analysis method with policy makers/key stakeholders to prioritize cardiovascular
      disease (CVD) policies in four Mediterranean countries: Palestine, Syria, Tunisia
      and Turkey. METHODS: A simple multi-criteria decision analysis (MCDA) method was
      piloted. A mixed methods study was used to identify a preliminary list of policy
      options in each country. These policies were rated by different
      policymakers/stakeholders against pre-identified criteria to generate a priority
      score for each policy and then rank the policies. RESULTS: Twenty-five different
      policies were rated in the four countries to create a country-specific list of
      CVD prevention and control policies. The response rate was 100% in each country.
      The top policies were mostly population level interventions and health systems'
      level policies. CONCLUSIONS: Successful collaboration between policy
      makers/stakeholders and researchers was established in this small pilot study.
      MCDA appeared to be feasible and effective. Future applications should aim to
      engage a larger, representative sample of policy makers, especially from outside
      the health sector. Weighting the selected criteria might also be assessed.

PMID- 24879321
TI  - The spatial coherence function in scanning transmission electron microscopy and
      spectroscopy.
AB  - We investigate the implications of the form of the spatial coherence function,
      also referred to as the effective source distribution, for quantitative analysis
      in scanning transmission electron microscopy, and in particular for interpreting
      the spatial origin of imaging and spectroscopy signals. These questions are
      explored using three different source distribution models applied to a GaAs
      crystal case study. The shape of the effective source distribution was found to
      have a strong influence not only on the scanning transmission electron microscopy
      (STEM) image contrast, but also on the distribution of the scattered electron
      wavefield and hence on the spatial origin of the detected electron intensities.
      The implications this has for measuring structure, composition and bonding at
      atomic resolution via annular dark field, X-ray and electron energy loss STEM
      imaging are discussed. 

PMID- 24879320
TI  - Identification of key residues that confer Rhodobacter sphaeroides LPS activity
      at horse TLR4/MD-2.
AB  - The molecular determinants underpinning how hexaacylated lipid A and
      tetraacylated precursor lipid IVa activate Toll-like receptor 4 (TLR4) are well
      understood, but how activation is induced by other lipid A species is less clear.
      Species specificity studies have clarified how TLR4/MD-2 recognises different
      lipid A structures, for example tetraacylated lipid IVa requires direct
      electrostatic interactions for agonism. In this study, we examine how
      pentaacylated lipopolysaccharide from Rhodobacter sphaeroides (RSLPS) antagonises
      human TLR4/MD-2 and activates the horse receptor complex using a computational
      approach and cross-species mutagenesis. At a functional level, we show that RSLPS
      is a partial agonist at horse TLR4/MD-2 with greater efficacy than lipid IVa.
      These data suggest the importance of the additional acyl chain in RSLPS
      signalling. Based on docking analysis, we propose a model for positioning of the
      RSLPS lipid A moiety (RSLA) within the MD-2 cavity at the TLR4 dimer interface,
      which allows activity at the horse receptor complex. As for lipid IVa, RSLPS
      agonism requires species-specific contacts with MD-2 and TLR4, but the R2 chain
      of RSLA protrudes from the MD-2 pocket to contact the TLR4 dimer in the vicinity
      of proline 442. Our model explains why RSLPS is only partially dependent on horse
      TLR4 residue R385, unlike lipid IVa. Mutagenesis of proline 442 into a serine
      residue, as found in human TLR4, uncovers the importance of this site in RSLPS
      signalling; horse TLR4 R385G/P442S double mutation completely abolishes RSLPS
      activity without its counterpart, human TLR4 G384R/S441P, being able to restore
      it. Our data highlight the importance of subtle changes in ligand positioning,
      and suggest that TLR4 and MD-2 residues that may not participate directly in
      ligand binding can determine the signalling outcome of a given ligand. This
      indicates a cooperative binding mechanism within the receptor complex, which is
      becoming increasingly important in TLR signalling. 

PMID- 24879322
TI  - Identification of a high affinity selective inhibitor of Polo-like kinase 1 for
      cancer chemotherapy by computational approach.
AB  - Polo-like kinase (Plk)1 is a key regulator of the cell cycle during mitotic phase
      and is an attractive anti-mitotic drug target for cancer. Plk1 is a member of
      Ser/Thr kinase family which also includes Plk2-4 in human. Plk1 promotes the cell
      division whereas Plk2 and Plk3 are reported to act as tumour suppressors. The
      available inhibitors of Plk1 also suppress Plk2 and Plk3 activity significantly
      resulting in the cell death of normal cells in addition to the cancer cells.
      Hence, it is imperative to explore Plk1 specific inhibitors as anti-cancer drugs.
      In this work, a selective potential inhibitor of Plk1 has been identified by
      molecular docking based high throughput virtual screening. The identified
      compound exploits the subtle differences between the binding sites of Plk1 and
      other Ser/Thr kinases including Plk2-4. The predicted binding affinity of
      identified inhibitor is higher than available inhibitors with a 100-fold
      selectivity towards Plk1 over Plk2-4 and several cell cycle kinases. It also
      satisfies the Lipinski's criteria of drug-like molecules and passes the other
      ADMET filters. This triazole compound with aryl substituent belongs to a novel
      class of potential inhibitor for Plk1. The suggested potential lead molecule can
      thus be tested and developed further as a potent and selective anti-cancer drug. 

PMID- 24879323
TI  - New in silico insights into the inhibition of RNAP II by alpha-amanitin and the
      protective effect mediated by effective antidotes.
AB  - Poisonous alpha-amanitin-containing mushrooms are responsible for the major cases
      of fatalities after mushroom ingestion. alpha-Amanitin is known to inhibit the
      RNA polymerase II (RNAP II), although the underlying mechanisms are not fully
      understood. Benzylpenicillin, ceftazidime and silybin have been the most
      frequently used drugs in the management of alpha-amanitin poisoning, mostly based
      on empirical rationale. The present study provides an in silico insight into the
      inhibition of RNAP II by alpha-amanitin and also on the interaction of the
      antidotes on the active site of this enzyme. Docking and molecular dynamics (MD)
      simulations combined with molecular mechanics-generalized Born surface area
      method (MM-GBSA) were carried out to investigate the binding of alpha-amanitin
      and three antidotes benzylpenicillin, ceftazidime and silybin to RNAP II. Our
      results reveal that alpha-amanitin should affects RNAP II transcription by
      compromising trigger loop (TL) function. The observed direct interactions between
      alpha-amanitin and TL residues Leu1081, Asn1082, Thr1083, His1085 and Gly1088
      alters the elongation process and thus contribute to the inhibition of RNAP II.
      We also present evidences that alpha-amanitin can interact directly with the
      bridge helix residues Gly819, Gly820 and Glu822, and indirectly with His816 and
      Phe815. This destabilizes the bridge helix, possibly causing RNAP II activity
      loss. We demonstrate that benzylpenicillin, ceftazidime and silybin are able to
      bind to the same site as alpha-amanitin, although not replicating the unique
      alpha-amanitin binding mode. They establish considerably less intermolecular
      interactions and the ones existing are essential confine to the bridge helix and
      adjacent residues. Therefore, the therapeutic effect of these antidotes does not
      seem to be directly related with binding to RNAP II. RNAP II alpha-amanitin
      binding site can be divided into specific zones with different properties
      providing a reliable platform for the structure-based drug design of novel
      antidotes for alpha-amatoxin poisoning. An ideal drug candidate should be a
      competitive RNAP II binder that interacts with Arg726, Ile756, Ala759, Gln760 and
      Gln767, but not with TL and bridge helix residues. 

PMID- 24879324
TI  - Response to: predictive role of neutrophil-to-lymphocyte ratio in Henoch
      Schonlein purpura-related gastrointestinal bleeding.

PMID- 24879327
TI  - Non-Fickian diffusion and the accumulation of methane bubbles in deep-water
      sediments.
AB  - In the absence of fractures, methane bubbles in deep-water sediments can be
      immovably trapped within a porous matrix by surface tension. The dominant
      mechanism of transfer of gas mass therefore becomes the diffusion of gas
      molecules through porewater. The accurate description of this process requires
      non-Fickian diffusion to be accounted for, including both thermal diffusion and
      gravitational action. We evaluate the diffusive flux of aqueous methane
      considering non-Fickian diffusion and predict the existence of extensive bubble
      mass accumulation zones within deep-water sediments. The limitation on the
      hydrate deposit capacity is revealed; too weak deposits cannot reach the base of
      the hydrate stability zone and form any bubbly horizon. 

PMID- 24879326
TI  - Intraorbital injection of Rituximab in idiopathic orbital inflammatory syndrome:
      case reports.
AB  - To analyze the clinical and histopathological effects of low doses of
      intraorbital and intralesional Rituximab (RTX) in three patients affected by
      idiopathic orbital inflammatory syndrome (IOIS). Three patients with IOIS were
      enrolled, all of whom underwent lesion biopsy to confirm the diagnosis, complete
      blood examinations (thyroid function tests, complete blood cell count, fasting
      blood glucose, liver and renal function tests, erythrocyte sedimentation rate,
      serum ACE, C-reactive protein, rheumatoid factor, antinuclear antibody,
      antineutrophil cytoplasmic antibody, serum IGg4 level tests) and magnetic
      resonance imaging (MRI). Patients received the planned treatment schedule,
      consisting of a complete cycle of intraorbital injections of RTX (MabThera((r));
      Roche, Basel, Switzerland, 100 mg/10 ml): 10 mg, once a week for 1 month (four
      injections/month), in two patients repeated. The clinical and imaging follow-ups
      were at an average of 17.6 months (range 14-24 months) after treatment. A post
      treatment bioptic procedure was performed in one patient. All patients showed a
      significant MRI reduction of the orbital lesion and a stable clinical improvement
      for the follow-up time of observation. The post-treatment histopathological
      specimen showed a disappearance of inflammatory cells. Low doses of intralesional
      RTX, which are safe, efficacious and used in other B cell-mediated disorders, are
      a useful treatment in IOIS, with decreased risks of generalized immunosuppression
      and fewer side effects than are afforded by systemic high doses of
      glucocorticoids and RTX. The result is very quick, effective and prolonged on the
      inflammatory component of the disease and seems to be related to the histologic
      reduction of infiltrating CD20+ lymphocytes.

PMID- 24879329
TI  - Primary adenosquamous carcinoma of ampulla of Vater-A rare case report.
AB  - INTRODUCTION: Primary adenosquamous carcinoma (ASC) of the ampulla of Vater (AmV)
      is extremely rare. Carcinoma of the ampulla of Vater tends to manifest early due
      to biliary outflow obstruction, as opposed to pancreatic neoplasms that often are
      advanced at the time of diagnosis. Periampullary carcinomas are treated by
      pancreaticoduodenectomy (PD). Adenosquamous carcinoma carries very dismal
      prognosis. PRESENTATION OF CASE: Here we present a case of 58-year-old male who
      was presented with abdominal pain, jaundice and anorexia with no history of (h/o)
      pruritus and clay colored stool. All blood investigations were normal except
      liver function tests (LFTs). Ultrasonography (USG) of abdomen suggestive of
      periampullary mass with dilated pancreatico-biliary tree. Endoscopic retrograde
      cholangiopancreatography (E.R.C.P.) demonstrated large deformed and bulky papilla
      with ulcerated lesion with infiltration in to duodenum. Exploratory laprotomy
      proceeds Whipple's pancreaticoduodenectomy done. Histopathology revealed
      adenocarcinoma of the ampulla of Vater. Immunohistochemistry was confirmatory of
      adenosquamous carcinoma. DISCUSSION: Adenosquamous carcinoma (ASC) is defined as
      a tumor in which both glandular and squamous elements are histologically
      malignant. Compared to adenocarcinoma, ASC of the AmV is a rare malignancy.
      Preoperative diagnosis is difficult because of the lack of defining
      characteristics in imaging studies and the difficulty in acquiring both malignant
      components by limited biopsy. Periampullary carcinomas are treated by
      pancreaticoduodenectomy. CONCLUSION: Adenosquamous carcinoma is a very rare form
      of cancer of the AmV. Pancreaticoduodenectomy is the treatment of choice though
      early recurrence and distal metastasis may be encountered after surgery. Follow
      up should be more frequent to detect possible early recurrence and distal
      metastasis.

PMID- 24879330
TI  - Total sacrectomy for recurrent rectal cancer - A case report featuring technical
      details and potential pitfalls.
AB  - INTRODUCTION: Total sacrectomy for recurrent rectal cancer is controversial.
      However, recent publications suggest encouraging outcomes with high sacral
      resections. We present the first case report describing technical aspects,
      potential pitfalls and treatment of complications associated with total
      sacrectomy performed as a treatment of recurrent rectal cancer. PRESENTATION OF
      CASE: A fifty-three year old man was previously treated at another institution
      with a low anterior resection (LAR) followed by chemo-radiation and left liver
      tri-segmentectomy for metastatic rectal cancer. Three years following the LAR,
      the patient developed a recurrence at the site of colorectal anastomosis,
      manifesting clinically as a contained perforation, forming a recto-cutaneous
      fistula through the sacrum. Abdomino-perineal resection (APR) and complete
      sacrectomy were performed using an anterior-posterior approach with posterior
      spinal instrumented fusion and pelvic fixation using iliac crest bone graft. Left
      sided vertical rectus abdominis muscle flap and right sided gracilis muscle flap
      were used for hardware coverage and to fill the pelvic defect. One year after the
      resection, the patient remains disease free and has regained the ability to move
      his lower limbs against gravity. DISCUSSION: The case described in this report
      features some formidable challenges due to the previous surgeries for metastatic
      disease, and the presence of a recto-sacral cutaneous fistula. An approach with
      careful surgical planning including considerationof peri-operative embolization
      is vital for a successful outcome of the operation. A high degree of suspicion
      for pseudo-aneurysms formation due infection or dislodgement of metallic coils is
      necessary in the postoperative phase. CONCLUSION: Total sacrectomy for the
      treatment of recurrent rectal cancer with acceptable short-term outcomes is
      possible.A detailed explanation to the patient of the possible complications and
      expectations including the concept of a very high chancefor recurrence is
      paramount prior to proceeding with such a surgery.

PMID- 24879328
TI  - Diversity of congenital cardiac defects and skeletal deformities associated with
      the Holt-Oram syndrome.
AB  - INTRODUCTION: The Holt-Oram syndrome is a rare congenital disorder involving the
      skeletal and cardiovascular systems. It is characterized by upper limb
      deformities and cardiac malformations, atrial septal defects in particular.
      PRESENTATION OF CASE: Four consecutive patients 1-15 years old with the Holt-Oram
      syndrome presented over a 10 year span for surgical treatment of their cardiac
      maladies. The spectrum of the heart defects and skeletal deformities encountered
      in these patients are described and discussed. DISCUSSION: The Holt-Oram syndrome
      is an autosomal dominant condition; however absence of the morphological features
      of the trait in close family members is not rare. Although patients are known to
      predominately present with atrial septal defects, other cardiovascular anomalies,
      including rhythm abnormalities, are not uncommon. Skeletal disorders vary as
      well. CONCLUSION: Cardiovascular disorders, skeletal malformations and familial
      expression of the Holt-Oram syndrome, vary widely.

PMID- 24879325
TI  - Non-invasive and in vivo assessment of osteoarthritic articular cartilage: a
      review on MRI investigations.
AB  - Early detection of knee osteoarthritis (OA) is of great interest to orthopaedic
      surgeons, rheumatologists, radiologists, and researchers because it would allow
      physicians to provide patients with treatments and advice to slow the onset or
      progression of the disease. Early detection can be achieved by identifying early
      changes in selected features of degenerative articular cartilage (AC) using non
      invasive imaging modalities. Magnetic resonance imaging (MRI) is becoming the
      standard for assessment of OA. The aim of this paper was to review the influence
      of MRI on the selection, detection, and measurement of AC features associated
      with early OA. Our review of the literature indicates that the changes associated
      with early OA are in cartilage thickness, cartilage volume, cartilage water
      content, and proteoglycan content that can be accurately, consistently, and non
      invasively measured using MRI. Choosing an MR pulse sequence that provides the
      capability to assess cartilage physiology and morphology in a single acquisition
      and advanced multi-nuclei MRI is desirable. The results of the review indicate
      that using an ultra-high magnetic strength, MR imager does not affect early OA
      detection. In conclusion, MRI is currently the most suitable modality for early
      detection of knee OA, and future research should focus on the quantitative
      evaluation of early OA features using advances in MR hardware, software, and data
      processing with sophisticated image/pattern recognition techniques. 

PMID- 24879331
TI  - Physician assistants in Australia.

PMID- 24879332
TI  - The future of physician assistant data?

PMID- 24879334
TI  - Enhancing near IR luminescence of thiolate Au nanoclusters by thermo treatments
      and heterogeneous subcellular distributions.
AB  - A five-to-ten fold enhancement, up to ca. 5-10% quantum efficiency, of near IR
      luminescence from monothiolate protected gold nanoclusters was achieved by
      heating in the presence of excess ligand thiols. An emission maximum in the 700
      900 nm range makes these Au nanoclusters superior for bioimaging applications
      over other emissions centered below 650 nm due to reduced background
      interference, albeit visible emissions could have higher quantum efficiency. The
      heating procedure is shown to be effective to improve the luminescence of Au
      nanoclusters synthesized under a variety of conditions using two types of
      monothiols: mercaptosuccinic acid and tiopronin. Therefore, this heating method
      is believed to be a generalizable approach to improve the near IR luminescence of
      aqueous soluble Au nanoclusters, which enables better bioimaging applications.
      The high quantum yield is found relatively stable over a wide pH range.
      PEGylation of the Au nanoclusters reduces their quantum efficiency but improves
      their permeation into the cytoplasm. Interestingly, z-stack confocal analysis
      clearly reveals the presence of Au nanoclusters inside the cell nucleus in single
      cell imaging. The finding addresses controversial literature reports and
      demonstrates the internalization and heterogeneous subcellular distributions,
      particularly inside the nucleus. The high luminescence intensity, small overall
      dimension, cell and nuclear distribution, chemical stability and low-to-non
      toxicity make these Au nanoclusters promising probes for broad cell dynamics and
      imaging applications. 

PMID- 24879333
TI  - Investigational Aurora A kinase inhibitor alisertib (MLN8237) as an enteric
      coated tablet formulation in non-hematologic malignancies: phase 1 dose
      escalation study.
AB  - BACKGROUND: This phase 1b study evaluated an enteric-coated tablet (ECT)
      formulation of the investigational Aurora A kinase inhibitor, alisertib
      (MLN8237). METHODS: Patients with advanced, non-hematologic malignancies received
      oral alisertib ECT for 7 d BID followed by 14 d treatment-free (21-day cycles; 3
      + 3 dose escalation schema). Objectives were to assess safety, pharmacokinetics,
      and antitumor activity, and to define a recommended phase 2 dose (RP2D) of
      alisertib. RESULTS: 24 patients were treated. Median age was 57 years. Patients
      received a median of 2 cycles (range 1-12). The RP2D was determined as 50 mg BID
      for 7 d (21-day cycles). A cycle 1 dose-limiting toxicity of grade 4 febrile
      neutropenia was observed in 1 of 13 patients at RP2D. The most common drug
      related adverse event (AE) was neutropenia (50%). At doses >= 40 mg BID, 7
      patients had drug-related AEs that were serious but largely reversible/manageable
      by dose reduction and supportive care, including 3 with febrile neutropenia.
      Pharmacokinetic data were available in 24 patients. Following administration of
      alisertib ECT, the plasma peak concentration of alisertib was achieved at ~3 h;
      systemic exposure increased with increasing dose over 10-60 mg BID. Mean t1/2 was
      ~21 h following multiple dosing. Renal clearance was negligible. Nine patients
      achieved stable disease (3.98*, 5.59, 1.28*, 2.56, 5.45*, 3.48, 3.15, 8.31, and
      6.93* months; *censored). CONCLUSIONS: Alisertib ECT was generally well tolerated
      in adults with advanced, non-hematologic malignancies. The RP2D is 50 mg BID for
      7 d and is being evaluated in ongoing phase 2 studies.

PMID- 24879336
TI  - Developmental dysplasia of the hip: incidence and treatment outcomes in the
      Southeast of Ireland.
AB  - BACKGROUND: The incidence of developmental dysplasia of the hip (DDH) in the
      Republic of Ireland is unknown. It has been shown by previous Irish studies that
      effective screening methods for DDH are not widely practiced. The effect of this
      on treatment outcomes is unknown. AIMS: The aim of this study was to estimate the
      incidence and treatment outcomes of DDH in the Southeast of Ireland. METHODS: In
      a retrospective study, all cases of DDH in children born in 2009 were identified
      using the outpatient clinic database. We defined an early and late diagnosis as
      those treated before and after three months, respectively. We defined the
      operative incidence as those who required open surgery. RESULTS: Fifty-six cases
      of DDH were diagnosed giving an incidence of 6.73 per 1,000 live births. 58.9% (n
      = 33) were referred to the clinic and began treatment early, while 41.1% (n = 23)
      presented late. The incidence of operative procedures was 1.08 per 1,000 live
      births. The incidence of those requiring surgery was higher in the late diagnosis
      group. CONCLUSION: Our overall incidence rate of 6.73 per 1,000 live births in
      2009 is similar to other international studies. Worryingly our incidence of 2.77
      per 1,000 having late diagnosis and 1.08 per 1,000 live births requiring open
      surgery was higher. Despite screening with clinical examination, the percentage
      of late diagnosis remains high. There is a need for the development of a national
      screening policy with greater use of ultrasound screening to improve current
      practices.

PMID- 24879335
TI  - Characterization of microparticles after hepatic ischemia-reperfusion injury.
AB  - BACKGROUND: Hepatic ischemia-reperfusion (I/R) is a well-studied model of liver
      injury and has demonstrated a biphasic injury followed by recovery and
      regeneration. Microparticles (MPs) are a developing field of study and these
      small membrane bound vesicles have been shown to have effector function in other
      physiologic and pathologic states. This study was designed to quantify the levels
      of MPs from various cell origins-platelets, neutrophils, and endolethial cells
      following hepatic ischemia-reperfusion injury. METHODS: A murine model was used
      with mice undergoing 90 minutes of partial hepatic ischemia followed by various
      times of reperfusion. Following reperfusion, plasma samples were taken and MPs of
      various cell origins were labeled and levels were measured using flow cytometry.
      Additionally, cell specific MPs were further assessed by Annexin V, which stains
      for the presence of phosphatidylserine, a cell surface marker linked to
      apoptosis. Statistical analysis was performed using one-way analysis of variance
      with subsequent Student-Newman-Keuls test with data presented as the mean and
      standard error of the mean. RESULTS: MPs from varying sources show an increase in
      circulating levels following hepatic I/R injury. However, the timing of the
      appearance of different MP subtypes differs for each cell type. Platelet and
      neutrophil-derived MP levels demonstrated an acute elevation following injury
      whereas endothelial-derived MP levels demonstrated a delayed elevation.
      CONCLUSION: This is the first study to characterize circulating levels of cell
      specific MPs after hepatic I/R injury and suggests that MPs derived from
      platelets and neutrophils serve as markers of inflammatory injury and may be
      active participants in this process. In contrast, MPs derived from endothelial
      cells increase after the injury response during the reparative phase and may be
      important in angiogenesis that occurs in the regenerating liver.

PMID- 24879337
TI  - Outcomes in gastric and junctional cancer using neoadjuvant and adjuvant
      chemotherapy (epirubicin, oxaliplatin, and capecitabine) and radical surgery.
AB  - BACKGROUND: The MAGIC/UK Medical Research Council (MRC) trial set the standard of
      care for treatment of resectable gastric and junctional adenocarcinoma,
      demonstrating that perioperative chemotherapy with epirubicin, cisplatin and 5
      fluorouracil (ECF) confers a survival benefit over surgery alone. The randomized
      ECF for advanced and locally advanced esophagogastric cancer (REAL-2) trial
      showed that, in the metastatic setting, the EOX regimen (epirubicin, oxaliplatin
      and capecitabine) is as effective as ECF, with a favourable toxicity profile.
      METHODS: Consecutive patients with resectable gastric or junctional
      adenocarcinoma treated with perioperative EOX, between 2007 and 2012, were
      retrospectively analysed. RESULTS: Fifty-nine patients (12 female, 47 male),
      commenced EOX therapy; 47 underwent surgery. A good pathological response was
      seen in 34%, (16/47). Disease recurrence occurred in 19 patients (19/47, 40%).
      Median overall survival was 22 months, with 4-year survival of 47%.
      Chemotoxicities were consistent with those previously reported for this regimen.
      CONCLUSION: This study in a high-volume centre demonstrates that EOX in
      resectable gastric and junctional adenocarcinoma is associated with a reasonable
      safety profile, and efficacy consistent with that reported for ECF.

PMID- 24879338
TI  - HER2 status in colorectal cancer: its clinical significance and the relationship
      between HER2 gene amplification and expression.
AB  - This study aimed at determining the incidence and clinical implications of HER2
      status in primary colorectal cancer (CRC). HER2 status was investigated in two
      retrospective cohorts of 365 consecutive CRC patients (cohort 1) and 174 advanced
      CRC patients with synchronous or metachronous distant metastasis (cohort 2). HER2
      status was determined by performing dual-color silver in-situ hybridization
      (SISH), mRNA in-situ hybridization (ISH), and immunohistochemistry (IHC). The
      incidence of HER2 protein overexpression (IHC 2+/3+) was approximately 6% (22 of
      365 in cohort 1; 10 of 174 in cohort 2). HER2 gene amplification was observed in
      5.8% of the patients from cohort 1 and 6.3% of the patients from cohort 2. HER2
      gene amplification was more frequently observed in CRCs located in the rectum
      than in the right and left colon (P = 0.013 in cohort 1; P = 0.009 in cohort 2).
      HER2 status, determined by IHC, ISH, and dual-color SISH, was not significantly
      associated with aggressive CRC behaviour or patients' prognosis in both the
      cohorts. Of the combined cohort with a total of 539 cases, the concordance rate
      was 95.5% between dual-color SISH and IHC detection methods. On excluding
      equivocally immunostained cases (IHC 2+), the concordance rate was 97.7%. HER2
      mRNA overtranscription, detected by ISH, significantly correlated with protein
      overexpression and gene amplification (P<0.001). HER2 gene amplification was
      identified in a minority of CRC patients with high concordance rates between dual
      color SISH and IHC detection methods. Although HER2 status did not predict
      patients' prognosis, our findings may serve as a basis for future studies on
      patient selection for HER2 targeted therapy.

PMID- 24879339
TI  - Mutation in KERA identified by linkage analysis and targeted resequencing in a
      pedigree with premature atherosclerosis.
AB  - AIMS: Genetic factors explain a proportion of the inter-individual variation in
      the risk for atherosclerotic events, but the genetic basis of atherosclerosis and
      atherothrombosis in families with Mendelian forms of premature atherosclerosis is
      incompletely understood. We set out to unravel the molecular pathology in a large
      kindred with an autosomal dominant inherited form of premature atherosclerosis.
      METHODS AND RESULTS: Parametric linkage analysis was performed in a pedigree
      comprising 4 generations, of which a total of 11 members suffered from premature
      vascular events. A parametric LOD-score of 3.31 was observed for a 4.4 Mb
      interval on chromosome 12. Upon sequencing, a non-synonymous variant in KERA
      (c.920C>G; p.Ser307Cys) was identified. The variant was absent from nearly 28,000
      individuals, including 2,571 patients with premature atherosclerosis. KERA, a
      proteoglycan protein, was expressed in lipid-rich areas of human atherosclerotic
      lesions, but not in healthy arterial specimens. Moreover, KERA expression in
      plaques was significantly associated with plaque size in a carotid-collar Apoe-/-
      mice (r2 = 0.69; p<0.0001). CONCLUSION: A rare variant in KERA was identified in
      a large kindred with premature atherosclerosis. The identification of KERA in
      atherosclerotic plaque specimen in humans and mice lends support to its potential
      role in atherosclerosis.

PMID- 24879342
TI  - Pancreatico-jejunal anastomosis with invaginating jenunal "J"-loop. Preliminary
      report of a new technique.
AB  - INTRODUCTION: The pancreatic anastomosis is the most demanding step after
      pancreaticoduodenectomy (PD) and the pancreatic fistula (PF) is the most dreaded
      complication. Many techniques have been investigated to assess the best way to
      deal with the pancreatic stump after PD and none of these has shown to be
      superior in terms of statistically significant reduction of PF rate. We report
      the preliminary experience of a new technique of pancreaticojejunostomy (PJ).
      METHODS: Fifteen patients underwent PD for neoplasms with end-to-side PJ with
      dunking jejunal "J"-loop, between July 2011 and March 2014. The data about their
      post-operative outcomes were analyzed. RESULTS: There were no intra-operative
      neither post-operative deaths. One patient had a grade A PF (6.7%). Total post
      operative complications occurred in 6 patients (40%), major post-operative
      complications occurred in 3 patients (20%). CONCLUSION: The new "sandwich"
      technique for dunking PJ after PD that we describe proved to be easy to perform
      and sure. It appears to be suitable for a dunking PJ when the diameter of the
      jejunum is too small than this of the pancreatic stump.

PMID- 24879341
TI  - Conservative interventions for treating middle third clavicle fractures in
      adolescents and adults.
AB  - BACKGROUND: Clavicle (collarbone) fractures account for around 4% of all
      fractures; treatment of these fractures is usually non-surgical (conservative).
      Commonly used treatments are arm slings, strapping, figure-of-eight bandages and
      splints.This is an update of a Cochrane review first published in 2009.
      OBJECTIVES: To evaluate the effects of different methods for conservative (non
      operative) treatment for acute (treated soon after injury) middle third clavicle
      fractures in adolescents and adults. SEARCH METHODS: We searched the Cochrane
      Bone, Joint and Muscle Trauma Group Specialised Register, the Cochrane Central
      Register of Controlled Trials (2013, Issue 12), MEDLINE (from 1966), EMBASE (from
      1980), LILACS (from 1982), trial registers, orthopaedic proceedings and reference
      lists of articles. We applied no language or publication restrictions. The date
      of the last search was 29 January 2014. SELECTION CRITERIA: Randomised and quasi
      randomised controlled trials testing conservative interventions for treating
      adolescents and adults with acute middle third clavicle fractures. The primary
      outcomes were shoulder function or disability, pain and treatment failure. DATA
      COLLECTION AND ANALYSIS: At least two authors selected eligible trials,
      independently assessed risk of bias and cross-checked data extraction. We
      calculated risk ratios and 95% confidence intervals for dichotomous variables,
      and mean differences and 95% confidence intervals for continuous variables. There
      was no pooling of data. MAIN RESULTS: We included three trials in this review
      with 354 participants. No new trials were included in this update.Very low
      quality evidence was available from two trials (234 participants) that compared
      the figure-of-eight bandage with an arm sling for treating acute middle third
      clavicle fractures. Both trials were underpowered and compromised by poor
      methodology. One trial found slightly higher pain levels in the bandage group at
      15 days (mean difference 0.80, 95% confidence interval 0.34 to 1.26; visual
      analogue scale: 0 (no pain) to 10 (worst pain)); and the other trial reported
      greater discomfort during bandage wear. There were no significant differences
      between the two interventions in functional or other outcomes reported for either
      trial.Moderate quality evidence was available from the third trial (120
      participants), which evaluated therapeutic ultrasound. This trial was at low risk
      of any type of bias but was underpowered. The trial found no statistically
      significant difference between low-intensity pulsed ultrasound and placebo in the
      time to clinical fracture healing (mean difference -0.32 days, 95% CI -5.85 to
      5.21 days), nor in any of the other reported outcomes. AUTHORS' CONCLUSIONS:
      There is limited evidence available from randomised controlled trials to
      determine which methods of conservative treatment are the most appropriate for
      acute middle third clavicle fractures in adolescents and adults. Further research
      is warranted.

PMID- 24879343
TI  - Laparoscopic common bile duct exploration and primary closure of choledochotomy
      after failed endoscopic sphincterotomy.
AB  - BACKGROUND: The aim of this study is to evaluate the safety and feasibility of
      laparoscopic common bile duct exploration and primary closure of choledochotomy
      for the patients with common bile duct stones (CBDS) who failed in endoscopic
      sphincterotomy (EST). METHODS: Between January 2007 and June 2012, a total of 78
      patients who subjected to endoscopic retrograde cholangiopancreatography (ERCP)
      and EST, but failed in endoscopic stone extraction, were referred to us. The
      following day, laparoscopic cholecystectomy, laparoscopic common bile duct
      exploration (LCBDE) and primary closure of choledochotomy were performed in all
      patients. RESULTS: No intraoperative complications were experienced in the
      patients. 6 patients required conversion to open cholecystectomy due to impacted
      stones. The mean operative time was 145 min. The mean postoperative hospital stay
      was 6d. All the patients achieved successful stone clearance. 13 cases had slight
      bile leaks, which resolved spontaneously. None of the patients experienced
      biliary peritonitis, biliary fistula, pancreatitis, or cholangitis. CONCLUSION:
      If it is performed by experienced laparoscopic surgeons, primary closure
      following immediate laparoscopic common bile duct exploration (LCBDE) is safe and
      feasible for patients with CBDS who fail in endoscopic stone extraction.

PMID- 24879340
TI  - Identification of two poorly prognosed ovarian carcinoma subtypes associated with
      CHEK2 germ-line mutation and non-CHEK2 somatic mutation gene signatures.
AB  - High-grade serous ovarian cancer (HG-SOC), a major histologic type of epithelial
      ovarian cancer (EOC), is a poorly-characterized, heterogeneous and lethal disease
      where somatic mutations of TP53 are common and inherited loss-of-function
      mutations in BRCA1/2 predispose to cancer in 9.5-13% of EOC patients. However,
      the overall burden of disease due to either inherited or sporadic mutations is
      not known. We performed bioinformatics analyses of mutational and clinical data
      of 334 HG-SOC tumor samples from The Cancer Genome Atlas to identify novel tumor
      driving mutations, survival-significant patient subgroups and tumor subtypes
      potentially driven by either hereditary or sporadic factors. We identified a sub
      cluster of high-frequency mutations in 22 patients and 58 genes associated with
      DNA damage repair, apoptosis and cell cycle. Mutations of CHEK2, observed with
      the highest intensity, were associated with poor therapy response and overall
      survival (OS) of these patients (P = 8.00e-05), possibly due to detrimental
      effect of mutations at the nuclear localization signal. A 21-gene mutational
      prognostic signature significantly stratifies patients into relatively low or
      high-risk subgroups with 5-y OS of 37% or 6%, respectively (P = 7.31e-08).
      Further analysis of these genes and high-risk subgroup revealed 2 distinct
      classes of tumors characterized by either germline mutations of genes such as
      CHEK2, RPS6KA2 and MLL4, or somatic mutations of other genes in the signature.
      Our results could provide improvement in prediction and clinical management of HG
      SOC, facilitate our understanding of this complex disease, guide the design of
      targeted therapeutics and improve screening efforts to identify women at high
      risk of hereditary ovarian cancers distinct from those associated with BRCA1/2
      mutations.

PMID- 24879344
TI  - Bacillus daqingensis sp. nov., a halophilic, alkaliphilic bacterium isolated from
      saline-sodic soil in Daqing, China.
AB  - An alkaliphilic, moderately halophilic, bacterium, designated strain X10-1(T),
      was isolated from saline-alkaline soil in Daqing, Heilongjiang Province, China.
      Strain X10-1(T) was determined to be a Gram-positive aerobe with rod-shaped
      cells. The isolate was catalase-positive, oxidase-negative, non-motile, and
      capable of growth at salinities of 0-16% (w/v) NaCl (optimum, 3%). The pH range
      for growth was 7.5-11.0 (optimum, pH 10.0). The genomic DNA G+C content was 47.7
      mol%. Its major isoprenoid quinone was MK-7 and its cellular fatty acid profile
      mainly consisted of anteiso-C15:0, anteiso-C17:0, iso-C15:0, C16:0, and iso
      C16:0. The peptidoglycan contained meso-diaminopimelic acid as the diagnostic
      diamino acid. The predominant polar lipids were diphosphatidylglycerol,
      phosphatidylethanolamine, and phosphatidylglycerol. Phylogenetic analysis based
      on 16S rRNA gene sequences showed that X10-1(T) is a member of the genus
      Bacillus, being most closely related to B. saliphilus DSM15402(T) (97.8%
      similarity) and B. agaradhaerens DSM 8721(T) (96.2%). DNA-DNA relatedness to the
      type strains of these species was less than 40%. On the basis of the
      phylogenetic, physiological, and biochemical data, strain X10-1(T) represents a
      novel species of the genus Bacillus, for which the name Bacillus daqingensis sp.
      nov. is proposed. The type strain is X10-1(T) (=NBRC 109404(T) = CGMCC
      1.12295(T)).

PMID- 24879345
TI  - Genotyping, morphology and molecular characteristics of a lytic phage of
      Neisseria strain obtained from infected human dental plaque.
AB  - The lytic bacteriaphage (phage) A2 was isolated from human dental plaques along
      with its bacterial host. The virus was found to have an icosahedron-shaped head
      (60+/-3 nm), a sheathed and rigid long tail (~175 nm) and was categorized into
      the family Siphoviridae of the order Caudovirales, which are dsDNA viral family,
      characterised by their ability to infect bacteria and are nonenveloped with a
      noncontractile tail. The isolated phage contained a linear dsDNA genome having
      31,703 base pairs of unique sequence, which were sorted into three contigs and 12
      single sequences. A latent period of 25 minutes and burst size of 24+/-2
      particles was determined for the virus. Bioinformatics approaches were used to
      identify ORFs in the genome. A phylogenetic analysis confirmed the species inter
      relationship and its placement in the family. 

PMID- 24879346
TI  - Bacillus cheonanensis sp. nov. isolated from near poultry farm soil [corrected].
AB  - A novel bacterial strain, designated PFS-5(T), was isolated from the soil
      environment with feces of a live poultry farm located in Cheonan, Republic of
      Korea. Strain PFS-5(T) was Gram-staining-positive, motile, strictly aerobic
      bacterium, rod-shaped, and endospore-forming. The strain contained meso
      diaminopimelic acid in their peptidoglycan and MK-7 menaquinone. The major fatty
      acids were anteiso-C15:0 (44.2%), C16:0 (22.2%), and iso-C15:0 (16.7%). The DNA
      G+C content was 40.1 mol%. Comparative 16S rRNA gene sequence analysis identified
      strain PFS-5(T) in the genus Bacillus, exhibiting the highest level of sequence
      similarity with type strain of B. herbersteinensis D-1,5a(T) (96.9%), B. humi LMG
      22167(T) (96.7%), B. alkalitelluris BA288(T) (96.1%), B. litoralis SW-211(T)
      (96.0%), and B. luteolus YIM93174(T) (95.5%). The major polar lipids of PFS-5(T)
      were diphosphatidylglycerol and phosphatidylglycerol. On the basis of result from
      poly-phasic data, strain PFS-5(T) represents a novel species, for which the name
      Bacillus cheonanensis sp. nov. is proposed (Type strai PFS-5(T) = KACC 17469(T) =
      JCM19333(T)). 

PMID- 24879347
TI  - Regional effects on chimera formation in 454 pyrosequenced amplicons from a mock
      community.
AB  - Chimeras are a frequent artifact in polymerase chain reaction and could be the
      underlying causes of erroneous taxonomic identifications, overestimated microbial
      diversity, and spurious sequences. However, little is known about the regional
      effects on chimera formation. Therefore, we investigated the chimera formation
      rates in different regions of phylogenetically important biomarker genes to test
      the regional effects on chimera formation. An empirical study of chimera
      formation rates was performed using the Roche GSFLXTM system with sequences of
      the V1/V2/V3 and V4/V5 regions of the 16S rRNA gene and sequences of the nifH
      gene from a mock microbial community. The chimera formation rates for the 16S
      V1/V2/V3 region, V4/V5 region, and nifH gene were 22.1-38.5%, 3.68-3.88%, and
      0.31-0.98%, respectively. Some amplicons from the V1/V2/V3 regions were shorter
      than the typical length (~7-31%), reflecting incomplete extension. In the
      V1/V2/V3 and V4/V5 regions, conserved and hypervariable regions were identified.
      Chimeric hot spots were located in parts of conserved regions near the ends of
      the amplicons. The 16S V1/V2/V3 region had the highest chimera formation rate,
      likely because of long template lengths and incomplete extension. The amplicons
      of the nifH gene had the lowest frequency of chimera formation most likely
      because of variations in their wobble positions in triplet codons. Our results
      suggest that the main reasons for chimera formation are sequence similarity and
      premature termination of DNA extension near primer regions. Other housekeeping
      genes can be a good substitute for 16S rRNA genes in molecular microbial studies
      to reduce the effects of chimera formation.

PMID- 24879348
TI  - A protective role of methionine-R-sulfoxide reductase against cadmium in
      Schizosaccharomyces pombe.
AB  - The Schizosaccharomyces pombe cells harboring the methionine- R-sulfoxide
      reductase (MsrB)-overexpressing recombinant plasmid pFMetSO exhibited better
      growth than vector control cells, when shifted into fresh medium containing
      cadmium chloride (abbreviated as Cd). Although both groups of cells contained
      enhanced reactive oxygen species (ROS) and nitric oxide (NO) levels in the
      presence of Cd, ROS and NO levels were significantly lower in the S. pombe cells
      harboring pFMetSO than in vector control cells. Conversely, the S. pombe cells
      harboring pFMetSO possessed higher total glutathione (GSH) levels and a greater
      reduced/oxidized GSH ratio than vector control cells under the same conditions. 

PMID- 24879349
TI  - Molecular characterization of atoxigenic Aspergillus flavus isolates collected in
      China.
AB  - Aspergillus flavus strains were isolated from peanut fields of Liaoning,
      Shandong, Hubei and Guangdong Provinces in China, and identified through
      phenotypic and molecular approaches. Of the 323 A. flavus strains isolated, 76
      strains did not produce aflatoxins detectable by UPLC. The incidence of
      atoxigenic A. flavus strains decreased with increase in temperature and increased
      with increase in latitude in different geographical locations. Amplification of
      all the aflatoxin genes in the aflatoxin gene cluster in the atoxigenic isolates
      showed that there were 25 deletion patterns (A-Y), with 22 deletion patterns
      identified for the first time. Most of the atoxigenic A. flavus isolates with
      gene deletions (97%) had deletions in at least one of the four genes (aflT, nor
      1, aflR, and hypB), indicating that these four genes could be targeted for rapid
      identification of atoxigenic strains. The atoxigenic isolates with gene
      deletions, especially the isolates with large deletions, are potential candidates
      for aflatoxin control.

PMID- 24879351
TI  - The innate responses of bumble bees to flower patterns: separating the nectar
      guide from the nectary changes bee movements and search time.
AB  - Nectar guides can enhance pollinator efficiency and plant fitness by allowing
      pollinators to more rapidly find and remember the location of floral nectar. We
      tested if a radiating nectar guide around a nectary would enhance the ability of
      naive bumble bee foragers to find nectar. Most experiments that test nectar guide
      efficacy, specifically radiating linear guides, have used guides positioned
      around the center of a radially symmetric flower, where nectaries are often
      found. However, the flower center may be intrinsically attractive. We therefore
      used an off-center guide and nectary and compared "conjunct" feeders with a
      nectar guide surrounding the nectary to "disjunct" feeders with a nectar guide
      separated from the nectary. We focused on the innate response of novice bee
      foragers that had never previously visited such feeders. We hypothesized that a
      disjunct nectar guide would conflict with the visual information provided by the
      nectary and negatively affect foraging. Approximately, equal numbers of bumble
      bees (Bombus impatiens) found nectar on both feeder types. On disjunct feeders,
      however, unsuccessful foragers spent significantly more time (on average 1.6-fold
      longer) searching for nectar than any other forager group. Successful foragers on
      disjunct feeders approached these feeders from random directions unlike
      successful foragers on conjunct feeders, which preferentially approached the
      combined nectary and nectar guide. Thus, the nectary and a surrounding nectar
      guide can be considered a combination of two signals that attract naive foragers
      even when not in the floral center. 

PMID- 24879350
TI  - Responses of Candida albicans to the human antimicrobial peptide LL-37.
AB  - Candida albicans is amajor fungal pathogen in humans. Antimicrobial peptides
      (AMPs) are critical components of the innate immune response in vertebrates and
      represent the first line of defense against microbial infection. LL-37 is the
      only member of the human family of cathelicidin AMPs and is commonly expressed by
      various tissues and cells, including surfaces of epithelia. The candidacidal
      effects of LL-37 have been well documented, but the mechanisms by which LL-37
      kills C. albicans are not completely understood. In this study, we examined the
      effects of LL-37 on cell wall and cellular responses in C. albicans. Using
      transmission electron microscopy, carbohydrate analyses, and staining for beta
      1,3-glucan, changing of C. albicans cell wall integrity was detected upon LL-37
      treatment. In addition, LL-37 also affected cell wall architecture of the
      pathogen. Finally, DNA microarray analysis and quantitative PCR demonstrated that
      sub-lethal concentrations of LL-37 modulated the expression of genes with a
      variety of functions, including transporters, regulators for biological
      processes, response to stress or chemical stimulus, and pathogenesis. Together,
      LL-37 induces complex responses in C. albicans, making LL-37 a promising
      candidate for use as a therapeutic agent against fungal infections. 

PMID- 24879352
TI  - David and Goliath: potent venom of an ant-eating spider (Araneae) enables capture
      of a giant prey.
AB  - It is rare to find a true predator that repeatedly and routinely kills prey
      larger than itself. A solitary specialised ant-eating spider of the genus
      Zodarion can capture a relatively giant prey. We studied the trophic niche of
      this spider species and investigated its adaptations (behavioural and venomic)
      that are used to capture ants. We found that the spider captures mainly
      polymorphic Messor arenarius ants. Adult female spiders captured large morphs
      while tiny juveniles captured smaller morphs, yet in both cases ants were giant
      in comparison with spider size. All specimens used an effective prey capture
      strategy that protected them from ant retaliation. Juvenile and adult spiders
      were able to paralyse their prey using a single bite. The venom glands of adults
      were more than 50 times larger than those of juvenile spiders, but the paralysis
      latency of juveniles was 1.5 times longer. This suggests that this spider species
      possesses very potent venom already at the juvenile stage. Comparison of the
      venom composition between juvenile and adult spiders did not reveal significant
      differences. We discovered here that specialised capture combined with very
      effective venom enables the capture of giant prey. 

PMID- 24879353
TI  - The phenomenology of controlling a moving object with another person.
AB  - The phenomenology of controlling what one perceives is influenced by a
      combination of sensory predictions and inferential processes. While it is known
      that external perturbations can reduce the sense of control over action effects,
      there have been few studies investigating the impact of intentional co-actors on
      the sense of control. In three experiments, we investigated how individuals'
      judgments of control (JoC) over a moving object were influenced by sharing
      control with a second person. Participants used joysticks to keep a cursor
      centered on a moving target either alone or with a co-actor. When both
      participants' actions had similar perceptual consequences, JoC ratings were
      highest when self-generated movements were the only influence on the cursor,
      while the appearance of sharing control with a second person decreased JoC
      ratings. By contrast, when participants performed complementary actions with
      perceptually distinctive consequences, JoC ratings were highest when both
      participants were able to influence the cursor. The phenomenology of control
      during joint action is influenced by low-level visuomotor correlations, the
      presence of competing causal influences, and group-level performance. 

PMID- 24879354
TI  - Single molecule confocal fluorescence lifetime correlation spectroscopy for
      accurate nanoparticle size determination.
AB  - We report on an experimental procedure in confocal single molecule fluorescence
      lifetime correlation spectroscopy (FLCS) to determine the range of excitation
      power and molecular or particulate concentration in solution under which the
      application of an unmodified model autocorrelation function is justified. This
      procedure enables fitting of the autocorrelation to an accurate model to measure
      diffusion length (r) and diffusion time (tauD) of single molecules in solution.
      We also report on the pinhole size dependency of r and tauD in a confocal FLCS
      platform. This procedure determines a set of experimental parameters with which
      the Stokes-Einstein (S-E) equation accurately measures the hydrodynamic radii of
      spherical nanoparticles, enabling the determination of the particle size range
      for which the hydrodynamic radius by the S-E equation measures the real particle
      radius. 

PMID- 24879356
TI  - Quantifying nitrous oxide fluxes on multiple spatial scales in the Upper Midwest,
      USA.
AB  - This study seeks to quantify the roles of soybean and corn plants and the
      cropland ecosystem in the regional N2O budget of the Upper Midwest, USA. The N2O
      flux was measured at three scales (plant, the soil-plant ecosystem, and region)
      using newly designed steady-state flow-through plant chambers, a flux-gradient
      micrometeorological tower, and continuous tall-tower observatories. Results
      indicate that the following. (1) N2O fluxes from unfertilized soybean (0.03 +/-
      0.05 nmol m(-2) s(-1)) and fertilized corn plants (-0.01 +/- 0.04 nmol m(-2) s(
      1)) were about one magnitude lower than N2O emissions from the soil-plant
      ecosystem (0.26 nmol m(-2) s(-1) for soybean and 0.95 nmol m(-2) s(-1) for corn),
      confirming that cropland N2O emissions were mainly from the soil. (2)
      Fertilization increased the corn plant flux for a short period (about 20 days),
      and late-season fertilization dramatically increased the soybean plant emissions.
      (3) The direct N2O emission from cropland accounted for less than 20 % of the
      regional flux, suggesting a significant influence by other sources and indirect
      emissions, in the regional N2O budget. 

PMID- 24879355
TI  - Two nested developmental waves demarcate a compartment boundary in the mouse
      lung.
AB  - The lung is a branched tubular network with two distinct compartments--the
      proximal conducting airways and the peripheral gas exchange region--separated by
      a discrete boundary termed the bronchoalveolar duct junction (BADJ). Here we
      image the developing mouse lung in three-dimensions (3D) and show that two nested
      developmental waves demarcate the BADJ under the control of a global hormonal
      signal. A first wave of branching morphogenesis progresses throughout embryonic
      development, generating branches for both compartments. A second wave of
      conducting airway differentiation follows the first wave but terminates earlier,
      specifying the proximal compartment and setting the BADJ. The second wave is
      terminated by a glucocorticoid signalling: premature activation or loss of
      glucocorticoid signalling causes a proximal or distal shift, respectively, in
      BADJ location. The results demonstrate a new mechanism of boundary formation in
      complex, 3D organs and provide new insights into glucocorticoid therapies for
      lung defects in premature birth.

PMID- 24879357
TI  - No effect of n-3 fatty acids supplementation on NT-proBNP after myocardial
      infarction: the Alpha Omega Trial.
AB  - BACKGROUND: heart failure is a major risk factor for cardiovascular mortality,
      for which n-3 fatty acids may have beneficial effects. We examined the effect of
      marine eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and plant
      derived alpha-linolenic acid (ALA) on N-Terminal-pro Brain Natriuretic Peptide
      (NT-proBNP), a biomarker of heart failure. METHODS: we randomly assigned 4837
      post-myocardial infarction patients, aged 60-80 years (82% men), to margarines
      supplemented with a targeted additional intake of 400 mg/day EPA and DHA, 2 g/day
      ALA, EPA-DHA plus ALA, or placebo for 40 months. In a random selection of 639
      patients, NT-proBNP was determined both at baseline and at the end of follow-up.
      NT-proBNP was loge-transformed and analysed by type of treatment using analysis
      of covariance adjusting for baseline NT-proNBP. RESULTS: patients consumed on
      average 19.8 g margarine/day, providing an additional amount of 238 mg/day EPA
      with 158 mg/day DHA, 1.98 g/day ALA, or both, in the active-treatment groups. In
      the placebo group, the geometric mean level NT-proBNP increased from 245 ng/l
      (95%-confidence interval [CI]: 207-290) to 294 ng/l (95%-CI: 244-352) after 40
      months (p = 0.001). NT-proBNP levels were not affected by ALA (+8% versus
      placebo; 95%-CI: -8% to +25%; p = 0.34), EPA-DHA (+2% versus placebo; 95%-CI: 
      14% to +18%; p = 0.78), nor EPA-DHA plus ALA (+9% versus placebo; 95%-CI: -8% to
      +25%; p = 0.31) treatment. CONCLUSIONS: supplementation with modest amounts of
      EPA-DHA, with or without ALA, did not have a significant effect on NT-proBNP
      levels in patients with a history of myocardial infarction.

PMID- 24879358
TI  - Insulin resistance predicts early cardiovascular morbidity in men without
      diabetes mellitus, with effect modification by physical activity.
AB  - AIM: to assess how well insulin resistance predicts cardiovascular disease (CVD)
      in non-diabetic men and women and to explore the influence of physical activity.
      METHODS: in this prospective study 2563 men and women without diabetes were
      examined with an oral glucose tolerance test, anthropometric measurements and
      blood pressure assessment. Questionnaires about lifestyle and physical activity
      were completed. Insulin resistance was estimated by fasting concentrations of
      plasma insulin and by HOMA index for insulin resistance. Participants were
      followed up for cardiovascular morbidity and mortality during an 8-year period,
      using information from the National Swedish Inpatient and Mortality registers.
      RESULTS: at follow-up, HOMAir predicted CVD morbidity in males (50 events) and
      females (28 events) combined (HRage/sex-adj 1.4, 95% CI 1.1-1.7); however, when
      stratified by gender HOMAir was predictive solely in men (HRage-adj 1.8, 95% CI
      1.3-2.4), whereas no association was found in women (HRage-adj 1.1, 95% CI 0.8
      1.5). When stratifying the data for high and low physical activity, the
      predictive value of insulin resistance became stronger in sedentary men (HRage
      adj 2.3, 95% CI 1.5-3.4) but was abolished in men performing moderate to vigorous
      physical activity (HRage-adj 1.0, 95% CI 0.6-1.6). The results remained when step
      wise adjusted also for BMI, ApoB/ApoA1 and hypertension, as well as for smoking,
      alcohol consumption and education. Outcome for fasting plasma insulin was similar
      to HOMAir. CONCLUSIONS: insulin resistance predicts CVD in the general
      population; however, men may be more vulnerable to increased insulin resistance
      than women, and physically inactive men seem to be at high risk.

PMID- 24879359
TI  - Risk factors for, and prevalence of, sleep apnoea in cardiac rehabilitation
      facilities in Germany: The Reha-Sleep registry.
AB  - AIM: To determine the prevalence of, and the risk factors for, sleep apnoea in
      cardiac rehabilitation (CR) facilities in Germany. METHODS: 1152 patients
      presenting for CR were screened for sleep-disordered breathing with 2-channel
      polygraphy (ApneaLinkTM; ResMed). Parameters recorded included the apnoea
      hypopnoea index (AHI), number of desaturations per hour of recording (ODI), mean
      and minimum nocturnal oxygen saturation and number of snoring episodes. Patients
      rated subjective sleep quality on a scale from 1 (poor) to 10 (best) and
      completed the Epworth Sleepiness Scale (ESS). RESULTS: Clinically significant
      sleep apnoea (AHI >=15/h) was documented in 33% of patients. Mean AHI was 14 +/-
      16/h (range 0-106/h). Sleep apnoea was defined as being of moderate severity in
      18% of patients (AHI >=15-29/h) and severe in 15% (AHI >=30/h). There were small,
      but statistically significant, differences in ESS score and subjective sleep
      quality between patients with and without sleep apnoea. Logistic regression model
      analysis identified the following as risk factors for sleep apnoea in CR
      patients: age (per 10 years) (odds ratio (OR) 1.51; p<0.001), body mass index
      (per 5 units) (OR 1.31; p=0.001), male gender (OR 2.19; p<0.001), type 2 diabetes
      mellitus (OR 1.45; p=0.040), haemoglobin level (OR 0.91; p=0.012) and witnessed
      apnoeas (OR 1.99; p<0.001). CONCLUSIONS: The findings of this study indicate that
      more than one-third of patients undergoing cardiac rehabilitation in Germany have
      sleep apnoea, with one-third having moderate-to-severe SDB that requires further
      evaluation or intervention. Inclusion of sleep apnoea screening as part of
      cardiac rehabilitation appears to be appropriate.

PMID- 24879360
TI  - Long term results after surgical management of posterior wall acetabular
      fractures.
AB  - BACKGROUND: Posterior wall fractures are the most common of all acetabular
      fractures, and there is universal consensus that displaced fractures are best
      treated with anatomical reduction and stable internal fixation. Though early and
      mid term results for such studies are available, few shed light on long term
      results. This study was performed to evaluate long term functional and
      radiological outcomes in patients with posterior wall acetabular fractures and to
      determine factors that may contribute adversely to a satisfactory final outcome.
      MATERIALS AND METHODS: We retrospectively analysed the hospital records for
      patients who underwent open reduction and internal fixation (ORIF) for posterior
      wall acetabular fractures. Twenty-five patients (20 men, five women), including
      one with bilateral posterior wall fracture, with a mean age of 41.28 +/- 7.16
      years (range 25-60 years) and a mean follow-up of 12.92 +/- 6.36 years (range 5
      22 years) who met the inclusion criteria formed the study cohort. Matta's
      criteria were used to grade postoperative reduction and final radiological
      outcome. Functional outcome at final follow-up was assessed according to
      d'Aubigne and Postel score. RESULTS: Anatomic reduction was achieved in 22 hips,
      imperfect in four and poor in none. Radiological outcome at final follow-up
      revealed excellent results in ten hips, good in eight, fair in five and poor in
      three. The final d'Aubigne and Postel scores were excellent in 14 hips, good in
      six and fair and poor in three each. Patients with anatomical reduction had a
      favourable functional and radiological long term outcome. However, the presence
      of associated injuries in lower limbs and a body mass index (BMI) >25 adversely
      affected the final functional outcome. Osteonecrosis was seen in three patients,
      heterotopic ossification in two and Morel Lavallee lesion in one. One patient had
      postoperative sciatic nerve palsy, which recovered 6 weeks after surgery.
      CONCLUSION: Anatomic postoperative reduction leads to optimal functional and
      radiological outcome on long term follow-up; however, the presence of associated
      lower-limb injuries and BMI >25 adversely affects a satisfactory final outcome in
      patients with posterior wall acetabular fractures. LEVEL OF EVIDENCE: (Level 4)
      Retrospective case series.

PMID- 24879361
TI  - Is intramedullary nailing more effective than non-operative treatment in adults
      with displaced middle-third clavicle fractures?
AB  - BACKGROUND: Clavicle fractures are common, accounting for 5-12 % of all
      fractures. Traditionally, displaced middle-third clavicle fractures have been
      managed non-operatively but the associated displacement often leads to mal-union
      with shortening, cosmetic deformity and occasionally non-union, with clinicians
      looking towards alternative operative methods such as intramedullary nailing
      (IMN). However, such methods have their own complications. In order to ascertain
      the effectiveness of IMN in the management of middle-third clavicle fractures
      compared with non-operative treatment, analysis of recent evidence is required
      and this review aims to achieve that, focusing on relevant, contemporary
      randomised-control trials. MATERIALS AND METHODS: Essential search-terms
      identified from the research question were used to formulate a search strategy. A
      systematic search of multiple databases was then performed from 1966 until
      present and appropriate papers for appraisal identified. RESULTS: Thirteen papers
      were identified, with 10 excluded using appropriate eligibility criteria. The
      remaining papers were then critically appraised. With regards shoulder function,
      all papers demonstrated an association between IMN and a significantly (P < 0.05)
      superior shoulder function score, but no consensus with regards to complication
      rates. However, all have identified limitations; therefore, their overall
      findings must be considered conservatively. CONCLUSIONS: Further, high-quality
      research, ideally in the form of well-designed, multi-centre RCTs is required to
      allow acceptable implementation of IMN of middle-third clavicle fractures into
      widespread practice. However, early results demonstrate that in young patients
      with displaced middle-third clavicle fractures, who are motivated to return to
      work, IMN provides superior functional results and should be considered. However,
      the importance of considering each patient individually as to their suitability
      for each management option, before coming to an informed decision with the
      patient rather than having a blanket approach to MTCF is essential. LEVEL OF
      EVIDENCE: Level 1.

PMID- 24879362
TI  - Phosphorus speciation in the marine sediment of Kalpakkam coast, southeast coast
      of India.
AB  - A study was carried out at Kalpakkam coast to find out the distribution of
      various fractions of phosphorus (P) in the marine sediment during pre-northeast
      monsoon period. Samples were collected from ten locations covering ~80 km(2) of
      the inner-shelf region. Sedimentary parameters such as sand, silt, clay, and
      organic carbon percentage were analyzed in order to find out their relation with
      various P fractions. The sediment was found to be predominantly sandy in nature
      with low silt and clay content. Among all the fractions (loosely bound (LoP),
      calcium bound (CaP), iron bound (FeP), aluminum bound (AlP), and organic (OP)),
      CaP fraction constituted the largest portion (68.7%) followed by organic fraction
      (16.3%). The bioavailable P fractions ranged from 5 to 44% of the total P (TP)
      content. Relatively high LoP content was observed at the offshore locations with
      comparatively high mud percentage as compared with the near-shore locations. As
      FeP and AlP concentrations were directly proportional to the amount of fine-grain
      sediment, the low levels of these fractions found in this coastal area were
      therefore attributed to the sandy nature of the sediments. The order of abundance
      of the major forms of P in the surface sediments of Kalpakkam coast was as
      follows: CaP > OP > LoP > AlP > FeP.

PMID- 24879363
TI  - Comparing spatial and temporal changes in metal trends (Cr, Ni, Pb and Zn) on the
      Portuguese shelf since the 1970s.
AB  - Comparison between an archive dataset, collected during the 1970s (1974-1977),
      and samples taken during the PALEO1 cruise (2002) enabled evaluation of large
      scale and long-term spatiotemporal changes in Al, Cr, Ni, Pb and Zn contents in
      bulk surface sediments in four areas of the Portuguese shelf. The so-called
      gradient method (GM) with normalisation to Al, a proxy for terrigenous clay
      content, was applied. The studied areas are distributed from north to south along
      the western margin, with the northernmost located off shore the Ave and Douro
      rivers, a central one located off shore the Lis River and a southern one located
      off shore the Mira River. One-way ANOVA and Kruskal-Wallis tests were used to
      identify differences among study areas and periods of sample collection. A
      comparison of metal contents in 2002 samples with the Portuguese classification
      scheme regulation for deposition of dredged materials in coastal areas indicates
      good environmental quality in terms of Cr, Ni, Pb and Zn levels. Nevertheless,
      the GM results suggest an increase in metal loadings relative to Al from the
      1970s to the 2002 samples (except for Pb). The Algarve area on the southern shelf
      is characterised by having high number of sites with metal level on class 2.
      These high values have traditionally been explained by a substantial supply of
      natural metals from the Guadiana, Tinto and Odiel rivers that drain areas Iberian
      Pyrite Belt formations. This supply has probably been magnified by present and
      past mining activities. For quality evaluation of marine sediments, especially
      when using total metal contents, this study shows the importance of considering
      all possible sources of metal loading. The natural grain size and composition
      variability have also a crucial influence on the metal content, and the combined
      evaluation allows a more holistic perspective. 

PMID- 24879364
TI  - Simple generation of albino C57BL/6J mice with G291T mutation in the tyrosinase
      gene by the CRISPR/Cas9 system.
AB  - Single nucleotide mutations (SNMs) are associated with a variety of human
      diseases. The CRISPR/Cas9 genome-editing system is expected to be useful as a
      genetic modification method for production of SNM-induced mice. To investigate
      whether SNM-induced mice can be generated by zygote microinjection of CRISPR/Cas9
      vector and single-stranded DNA (ssDNA) donor, we attempted to produce albino
      C57BL/6J mice carrying the Tyr gene SNM (G291T) from pigmented C57BL/6J zygotes.
      We first designed and constructed a CRISPR/Cas9 expression vector for the Tyr
      gene (px330-Tyr-M). DNA cleavage activity of px330-Tyr-M at the target site of
      the Tyr gene was confirmed by the EGxxFP system. We also designed an ssDNA donor
      for homology-directed repair (HDR)-mediated gene modification. The px330-Tyr-M
      vector and ssDNA donor were co-microinjected into the pronuclei of 224 one-cell
      stage embryos derived from C57BL/6J mice. We obtained 60 neonates, 28 of which
      showed the ocular albinism and absence of coat pigmentation. Genomic sequencing
      analysis of the albino mice revealed that the target of SNM, G291T in the Tyr
      gene, occurred in 11 mice and one founder was homozygously mutated. The remaining
      albino founders without Tyr G291T mutation also possessed biallelic deletion and
      insertion mutants adjacent to the target site in the Tyr locus. Simple production
      of albino C57BL/6J mice was provided by C57BL/6J zygote microinjection with px330
      Tyr-M DNA vector and mutant ssDNA (G291T in Tyr) donor. A combination of
      CRISPR/Cas9 vector and optional mutant ssDNA could be expected to efficiently
      produce novel SNM-induced mouse models for investigating human diseases. 

PMID- 24879366
TI  - The brominated flame retardants, PBDEs and HBCD, in Canadian human milk samples
      collected from 1992 to 2005; concentrations and trends.
AB  - Human milk samples were collected from individuals residing in various regions
      across Canada mostly in the years 1992 to 2005. These included five large cities
      in southern Canada as well as samples from Nunavik in northern Quebec.
      Comparative samples were also collected from residents of Austin, Texas, USA in
      2002 and 2004. More than 300 milk samples were analysed for the brominated flame
      retardants (BFRs), PBDEs and HBCD, by extraction, purification and quantification
      using either isotope dilution gas chromatography-mass spectrometry (GC-MS) or
      liquid chromatography-MS. The Canadian total PBDE values in the years 2002-2005
      show median levels of about 20MUg/kg on a lipid basis; a value significantly
      higher than in the 1980s and 1990s. Milk samples from Inuit donors in the
      northern region of Nunavik were slightly lower in PBDE concentrations than those
      from populated regions in the south of Quebec. Milk samples from Ontario
      contained slightly lower amounts of PBDEs in two time periods than those from
      Texas. HBCD levels in most milk samples were usually less than 1ppb milk lipid
      and dominated by the alpha-isomer. This large data set of BFRs in Canadian human
      milk demonstrates an increase in the last few decades in human exposure to BFRs
      which now appears to have stabilized. 

PMID- 24879367
TI  - Air pollution and human fertility rates.
AB  - BACKGROUND: Some reports have suggested effects of air pollution on semen quality
      and success rates of in vitro fertilization (IVF) in humans and lower fertility
      rates in mice. However, no studies have evaluated the impact of air pollution on
      human fertility rates. AIMS: We assessed the association between traffic related
      air pollution and fertility rates in humans in Barcelona, Spain (2011-2012). We
      hypothesized that higher air pollution levels would be associated with lower
      fertility rates. METHODS: We calculated the general fertility rate which is the
      number of live births per 1000 women between the ages of 15 and 44 years per
      census tract. We used land use regression (LUR) modeling to estimate the air
      pollution concentrations (particulate matter, NO2/NOx) per census tract. We used
      Besag-York-Mollie models to quantify the relationship between air pollution and
      fertility rates with adjustment for a number of potential confounders such as
      maternal age and area level socio-economic status. RESULTS: We found a
      statistically significant reduction of fertility rates with an increase in
      traffic related air pollution levels, particularly for the coarse fraction of
      particulate matter (IRR=0.87 95% CI 0.82, 0.94 per IQR). CONCLUSION: This is the
      first study in humans to show an association between reduced fertility rates and
      higher traffic related air pollution levels.

PMID- 24879368
TI  - Obesogenic effects of endocrine disruptors, what do we know from animal and human
      studies?
AB  - BACKGROUND: Hormonal actions and activation of receptors involved in adipogenesis
      and brain development during the prenatal period may be affected by exposure to
      certain chemicals. Experimental studies have shown that amongst others
      polychlorinated biphenyl (PCB)-153 and dichlorodiphenyltrichloroethane (DDT) may
      have obesogenic effects in prenatally exposed mice. OBJECTIVE: To provide an
      overview of five classes of chemicals which have frequently been indicated as
      potential obesogens, and to discuss the evidence available regarding early life
      exposure to these compounds and overweight later in life. METHODS: Pubmed was
      systematically searched for publications which related early life exposure to
      endocrine disrupting chemicals (EDCs) to growth parameters later in life. We
      included 19 studies, which were published from 1995 and onwards. RESULTS: Both
      positive and negative associations are observed between early life exposure and
      weight or height at various ages, including as early as 14 months, as well as
      until 20 years of age. In none of the included studies negative associations
      between perinatal exposure to EDCs and body mass index (BMI) were found and in
      several studies a positive association was observed. Dose-response relations
      appear to be non-monotonic. CONCLUSION: For certain EDCs, early life exposure may
      be associated with weight homeostasis later in life, however not necessarily in
      an obesogenic direction. More sensitive measures of adiposity as well as long
      term follow-up are warranted for future studies.

PMID- 24879369
TI  - Comparing measured and modelled PFOS concentrations in a UK freshwater catchment
      and estimating emission rates.
AB  - The lifecycle, sources and fate of perfluorooctane sulfonate (PFOS) continue to
      generate scientific and political interest, particularly since PFOS was listed by
      the Stockholm Convention and largely restricted in Europe. It continues to be
      detected in aquatic environments, with only limited studies into the on-going
      sources. This paper explores PFOS emissions discharged by the general population
      into a small catchment comprising two rivers in the UK. A sampling campaign was
      undertaken to improve our understanding of population-derived PFOS sources from
      sewage treatment plants (STPs) and in rivers. A corresponding modelling exercise
      allowed an emission estimate of 13MUg/day/per capita to be derived for the Aire
      and Calder rivers. PFOS emission was linked to STP discharges bylinear regression
      of measured and modelled concntrations (R(2)=0.49-0.85). The model was able to
      accurately estimate the spatial trends of PFOS in the rivers, while predicted
      concentrations were within a factor of three based on per capita emission values
      taken from the literature. Measured PFOS concentrations in rivers suggested that
      emissions from STPs are partially dependent on treatment type, where plants with
      secondary or tertiary treatment such as activated sludge processes emit less
      PFOS, possibly due to increased partitioning and retention. With refinements
      based on the type of treatment at each STP, predictions were further improved.
      The total PFOS mass discharged annually via rivers from the UK has been estimated
      to be between 215 and 310kg, based on the per capita emission range derived in
      this study. 

PMID- 24879370
TI  - Graphene-induced unusual microstructural evolution in Ag plated Cu foils.
AB  - Graphene-induced abnormal grain growth of Cu with a grain size of more than 1
      mm(2) was observed on Cu-Ag alloy foil, and this phenomenon occurred only with
      graphene synthesis and only on the Cu-Ag alloy among various types of Cu foils. 

PMID- 24879371
TI  - Cangrelor: review of the drug and the CHAMPION programme (including PHOENIX).
AB  - Platelet inhibition is the main goal of ancillary pharmacologic therapy during
      percutaneous coronary interventions (PCI). Thienopyridines and ticagrelor are
      oral drugs developed for this purpose. Cangrelor is an intravenous, non
      thienopyridine antagonist of the P2Y12 receptor with a rapid, potent,
      predictable, and quickly reversible effect. Cangrelor has been studied in a broad
      population intended to receive PCI in the CHAMPION program, where it was compared
      with different clopidogrel regimens. The first two trials, CHAMPION PCI and
      PLATFORM, failed their primary objective, likely for challenges in the
      adjudication of PCI-related myocardial infarction. In a third trial that
      implemented the universal definition of MI, CHAMPION PHOENIX, a reduction of
      thrombotic events, including stent thrombosis, was observed. In the BRIDGE trial
      cangrelor has been studied in patients who had to prematurely interrupt
      antiplatelet therapy for surgery. Cangrelor appears a promising agent in patients
      who require PCI or when a rapid reversal is needed. 

PMID- 24879372
TI  - Carpal tunnel syndrome diagnosis in occupational epidemiological studies.

PMID- 24879373
TI  - Association of physical workload and leisure time physical activity with incident
      mobility limitations: a follow-up study.
AB  - OBJECTIVES: To examine individual as well as joint associations of physical
      workload and leisure time physical activity with incident mobility limitations in
      initially well-functioning middle-aged workers. METHODS: This study is based on 6
      year follow-up data of the Danish Longitudinal Study on Work, Unemployment and
      Health. Physical workload was reported at baseline and categorised as light,
      moderate or heavy. Baseline leisure time physical activity level was categorised
      as sedentary or active following the current recommendations on physical
      activity. Incidence of mobility limitations in climbing stairs and running among
      initially well-functioning workers (n=3202 and n=2821, respectively) was assessed
      during follow-up. RESULTS: Higher workload increased whereas active leisure time
      decreased the risk of developing mobility limitations. The incidence of
      limitations increased progressively with higher workload regardless of level of
      leisure time physical activity, although the risks tended to be higher among
      those with sedentary leisure time compared with their active counterparts. All in
      all, the risk for onset of mobility limitations was highest among those with
      heavy workload combined with sedentary leisure time and lowest among those with
      light workload combined with active leisure time. CONCLUSIONS: Although leisure
      time physical activity prevents development of mobility decline, high workload
      seems to accelerate the progression of mobility limitations among both those with
      active and sedentary leisure time. Therefore, efforts should be made to recommend
      people to engage in physical activity regardless of their physical workload.

PMID- 24879374
TI  - Mycobacterium tuberculosis infection in young children: analyzing the performance
      of the diagnostic tests.
AB  - OBJECTIVE: This study evaluated the performance of the Tuberculin Skin Test (TST)
      and Quantiferon-TB Gold in-Tube (QFT) and the possible association of factors
      which may modify their results in young children (0-6 years) with recent contact
      with an index tuberculosis case. MATERIALS AND METHODS: A cross-sectional study
      including 135 children was conducted in Manaus, Amazonas-Brazil. The TST and QFT
      were performed and the tests results were analyzed in relation to the personal
      characteristics of the children studied and their relationship with the index
      case. RESULTS: The rates of positivity were 34.8% (TST) and 26.7% (QFT), with
      14.1% of indeterminations by the QFT. Concordance between tests was fair (Kappa =
      0.35 P<0.001). Both the TST and QFT were associated with the intensity of
      exposure (Linear OR = 1.286, P = 0.005; Linear OR = 1.161, P = 0.035
      respectively) with only the TST being associated with the time of exposure
      (Linear OR = 1.149, P = 0.009). The presence of intestinal helminths in the TST+
      group was associated with negative QFT results (OR = 0.064, P = 0.049). In the
      TST- group lower levels of ferritin were associated with QFT+ results (Linear OR
      = 0.956, P = 0.036). CONCLUSIONS: Concordance between the TST and QFT was lower
      than expected. The factors associated with the discordant results were intestinal
      helminths, ferritin levels and exposure time to the index tuberculosis case. In
      TST+ group, helminths were associated with negative QFT results suggesting
      impaired cell-mediated immunity. The TST-&QFT+ group had a shorter exposure time
      and lower ferritin levels, suggesting that QFT is faster and ferritin may be a
      potential biomarker of early stages of tuberculosis infection.

PMID- 24879375
TI  - Evaluation of osteopontin as a potential biomarker for central nervous system
      embryonal tumors.
AB  - Osteopontin (OPN) is a protein linked to tumor growth, progression and metastasis
      of cancers. However, its role in the progression of central nervous system (CNS)
      embryonal tumors such as atypical teratoid/rhabdoid tumor (AT/RT),
      medulloblastoma (MB) and primitive neuroepithelial tumors (PNET) remains elusive.
      In this study, we investigated the value of OPN staining in differential
      diagnosis of AT/RT from MB and PNET, and assessed the correlation between OPN
      expression and patients' prognosis. This retrospective study was conducted on
      tissue sections obtained from children cases with CNS embryonal tumors treated in
      Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine
      from 2006 to 2012 by immunohistochemistry (IHC). 49 cases were collected (11
      AT/RTs, 25 MBs, and 13 PNETs), with a median follow-up time of 28.9 months. OPN
      expression in AT/RT was significantly higher than MB and PNET with the positive
      rates of 100, 32, and 23 %, respectively (P < 0.01). The specificity and
      sensitivity of OPN staining in diagnosing AT/RT are 97.4 and 90.9 %,
      respectively, as judged by strong OPN IHC staining level (+++). Patients who had
      positive OPN staining have increased risks of poorer median overall survival
      (hazard risk 5.54, 95 % CI 1.87-16.38) and tumor progression (hazard risk 14.47,
      95 % CI 4.47-46.85). OPN is a valuable biomarker to aid in the differential
      diagnosis between AT/RT and MB/PNET. Moreover, OPN is a potential novel
      prognostic marker for CNS embryonal tumors.

PMID- 24879376
TI  - A new strategy of CyberKnife treatment system based radiosurgery followed by
      early use of adjuvant bevacizumab treatment for brain metastasis with extensive
      cerebral edema.
AB  - Bevacizumab blocks the effects of vascular endothelial growth factor in leakage
      prone capillaries and has been suggested as a new treatment for cerebral
      radiation edema and necrosis. CyberKnife is a new, frameless stereotactic
      radiosurgery system. This work investigated the safety and efficacy of CyberKnife
      followed by early bevacizumab treatment for brain metastasis with extensive
      cerebral edema. The eligibility criteria of the patients selected for
      radiosurgery followed by early use of adjuvant bevacizumab treatment were: (1)
      brain tumors from metastasis with one solitary brain lesion and symptomatic
      extensive cerebral edema; (2) >18 years of age; (3) the patient refused surgery
      due to the physical conditions and the risk of surgery; (4) no contraindications
      for bevacizumab. (5) bevacizumab was applied for a minimum of 2 injections and a
      maximum of 6 injections with a 2-week interval between treatments, beginning
      within 2 weeks of the CyberKnife therapy; (6) Karnofsky performance status (KPS)
      >=30. Tumor size and edema were monitored by magnetic resonance imaging (MRI).
      Dexamethasone dosage, KPS, adverse event occurrence and associated clinical
      outcomes were also recorded. Eight patients were accrued for this new treatment.
      Radiation dose ranged from 20 to 33 Gy in one to five sessions, prescribed to the
      61-71 % isodose line. Bevacizumab therapy was administered 3-10 days after
      completion of CyberKnife treatment for a minimum of two cycles (5 mg/kg, at 2
      week intervals). MRI revealed average reductions of 55.8 % (post-gadolinium) and
      63.4 % (T2/FLAIR). Seven patients showed significant clinical neurological
      improvements. Dexamethasone was reduced in all patients, with five successfully
      discontinuing dexamethasone treatment 4 weeks after bevacizumab initiation.
      Hypertension, a bevacizumab-related adverse event, occurred in one patient. After
      3-8 months, all patients studied were alive and primary brain metastases were
      under control, 2 developed new brain metastases and underwent salvage CyberKnife
      treatment. Recurrent edema and emerging radiation necrosis were not observed.
      CyberKnife radiosurgery followed by early use of bevacizumab is promising and
      appears safe for treatment of brain metastases with extensive cerebral edema.

PMID- 24879377
TI  - BRMS1 suppresses glioma progression by regulating invasion, migration and
      adhesion of glioma cells.
AB  - Breast cancer metastasis suppressor 1 (BRMS1) is a metastasis suppressor gene in
      several solid tumors. However, the expression and function of BRMS1 in glioma
      have not been reported. In this study, we investigated whether BRMS1 play a role
      in glioma pathogenesis. Using the tissue microarray technology, we found that
      BRMS1 expression is significantly decreased in glioma compared with tumor
      adjacent normal brain tissue (P<0.01, chi(2) test) and reduced BRMS1 staining is
      associated with WHO stages (P<0.05, chi(2) test). We also found that BRMS1 was
      significantly downregulated in glioma cell lines compared to normal human
      astrocytes (P<0.01, chi(2) test). Furthermore, we demonstrated that BRMS1
      overexpression inhibited glioma cell invasion by suppressing uPA, NF-kappaB, MMP
      2 expression and MMP-2 enzyme activity. Moreover, our data showed that
      overexpression of BRMS1 inhibited glioma cell migration and adhesion capacity
      compared with the control group through the Src-FAK pathway. Taken together, this
      study suggested that BRMS1 has a role in glioma development and progression by
      regulating invasion, migration and adhesion activities of cancer cells.

PMID- 24879378
TI  - Moving stimuli are less effectively masked using traditional continuous flash
      suppression (CFS) compared to a moving Mondrian mask (MMM): a test case for
      feature-selective suppression and retinotopic adaptation.
AB  - Continuous flash suppression (CFS) is a powerful interocular suppression
      technique, which is often described as an effective means to reliably suppress
      stimuli from visual awareness. Suppression through CFS has been assumed to depend
      upon a reduction in (retinotopically specific) neural adaptation caused by the
      continual updating of the contents of the visual input to one eye. In this study,
      we started from the observation that suppressing a moving stimulus through CFS
      appeared to be more effective when using a mask that was actually more prone to
      retinotopically specific neural adaptation, but in which the properties of the
      mask were more similar to those of the to-be-suppressed stimulus. In two
      experiments, we find that using a moving Mondrian mask (i.e., one that includes
      motion) is more effective in suppressing a moving stimulus than a regular CFS
      mask. The observed pattern of results cannot be explained by a simple simulation
      that computes the degree of retinotopically specific neural adaptation over time,
      suggesting that this kind of neural adaptation does not play a large role in
      predicting the differences between conditions in this context. We also find some
      evidence consistent with the idea that the most effective CFS mask is the one
      that matches the properties (speed) of the suppressed stimulus. These results
      question the general importance of retinotopically specific neural adaptation in
      CFS, and potentially help to explain an implicit trend in the literature to adapt
      one's CFS mask to match one's to-be-suppressed stimuli. Finally, the results
      should help to guide the methodological development of future research where
      continuous suppression of moving stimuli is desired. 

PMID- 24879379
TI  - Heat shock protein-27 delays acute rejection after cardiac transplantation: an
      experimental model.
AB  - BACKGROUND: Rejection is the major obstacle to survival after cardiac
      transplantation. We investigated whether overexpression of heat shock protein
      (Hsp)-27 in mouse hearts protects against acute rejection and the mechanisms of
      such protection. METHODS: Hearts from B10.A mice overexpressing human Hsp-27 (Hsp
      27tg), or Hsp-27-negative hearts from littermate controls (LCs) were transplanted
      into allogeneic C57BL/6 mice. The immune response to B10.A hearts was
      investigated using quantitative polymerase chain reaction for CD3+, CD4+, CD8+ T
      cells, and CD14+ monocytes and cytokines (interferon-gamma, interleukin [IL]-2,
      tumor necrosis factor-alpha, IL-1beta, IL-4, IL-5, IL-10, transforming growth
      factor-beta) in allografts at days 2, 5, and 12 after transplantation. The effect
      of Hsp-27 on ischemia-induced caspase activation and immune activation was
      investigated. RESULTS: Survival of Hsp-27tg hearts (35+/-10.37 days, n=10) was
      significantly prolonged compared with LCs (13.6+/-3.06 days, n=10, P=0.0004). Hsp
      27tg hearts expressed significantly more messenger RNA (mRNA) markers of CD14+
      monocytes at day 2 and less mRNA markers of CD3+ and CD8+T cells at day 5
      compared with LCs. There was more IL-4 mRNA in Hsp-27tg hearts at day 2 and less
      interferon-gamma mRNA at day 5 compared with LCs. Heat shock protein-27tg hearts
      subjected to ischemia or to 24 hr ischemia-reperfusion injury demonstrated
      significantly less apoptosis and activation of caspases 3, 9, and 1 than LCs. T
      cells removed from C57BL/6 recipients of Hsp-27tg hearts produced a vigorous
      memory response to B10.A antigens, suggesting immune activation was not inhibited
      by Hsp-27. CONCLUSION: Heat shock protein-27 delays allograft rejection, by
      inhibiting tissue damage, through probably an antiapoptotic pathway. It may also
      promote an anti-inflammatory subset of monocytes.

PMID- 24879380
TI  - Outcomes of kidney transplant tourism and risk factors for de novo urothelial
      carcinoma.
AB  - BACKGROUND: To date, the outcomes of transplant tourism have not been reported
      extensively. In addition, data about the accuracy of urine cytology for the
      detection and the role of the BK virus (BKV) in the carcinogenesis of urothelial
      carcinoma (UC) after renal transplantation are lacking. METHODS: Three hundred
      seven patients who received deceased donor kidney transplants between January
      2003 and December 2009 were retrospectively studied. The clinical parameters and
      outcomes between the domestic and tourist groups were compared. We also
      investigated the risk factors and role of BKV in the carcinogenesis of de novo UC
      by quantitative real-time polymerase chain reaction. RESULTS: The subjects in the
      tourist group were older at transplantation and had a shorter dialysis time
      before transplantation. There were significantly higher incidence rates of BKV
      viruria, Pneumocystis jiroveci pneumonia, and malignancy in the tourist group.
      Graft and patient survival were superior in the domestic group. A total of 43
      cancers were identified, and the most common type of malignancy was UC (23
      patients, 53.5%). The tourist group had a significantly higher incidence of
      tumors. The sensitivity and specificity of urine cytology for detecting UC were
      73.9% and 94.7%, respectively. Independent predictors of UC included female sex,
      use of Chinese herbal medicine, and transplant tourism. Only two patients (8.7%)
      with UC had detectable BKV. CONCLUSIONS: Transplant tourism was a risk factor for
      infection and de novo malignancy. Urothelial carcinoma was the most common
      malignancy after kidney transplantation. Regular screening for the early
      detection of UC by urine cytology or periodic sonographic surveys is mandatory,
      especially for those at high risk.

PMID- 24879382
TI  - Clinical assessment of mortality risk in renal transplant candidates in Spain.
AB  - BACKGROUND: Prediction of mortality in wait-listed patients for kidney
      transplantation (KT) has not been well elucidated. We assessed whether
      application of the Charlson comorbidity index (CCI) and other uremia-related
      comorbidities, not included in the CCI, were associated with mortality in these
      patients. METHODS: We included 3851 adult patients from the Andalusian Registry
      who were placed on the waiting list for KT during the study period (1984-2012). A
      total of 1975 patients received a successful KT and were censored at that point,
      whereas 1876 were on the waiting list at any time. Multivariate Cox proportional
      regression analysis and competing risk models, both of which included a
      propensity score for factors leading to KT, were constructed to examine death in
      wait-listed patients. RESULTS: Overall mortality on the waiting list was 24%, and
      cardiovascular disease was the leading cause of death (25%), followed by
      infections (19%) and malignant disorders (7%). By competing risk models, age
      older than 50 years (subhazard ratio [SHR] 1.4; 95% CI, 1.1-1.9), CCI score
      higher than 3 (SHR 2.8; 95% CI, 2.1-3.7), a central venous catheter (SHR 1.8; 95%
      CI, 1.4-2.2) and unemployed status (SHR 1.7; 95% CI, 1.3-2.2) at dialysis entry
      were significantly associated with mortality. When these factors were
      incorporated in a composite risk model, mortality risk increased significantly
      with increasing risk levels. CONCLUSION: A limited number of comorbidities,
      easily measurable at entry to dialysis, are associated with mortality in wait
      listed patients. This simple clinical assessment may help prioritize high-risk
      wait-listed patients for receiving an age-matched deceased donor kidney.

PMID- 24879381
TI  - Effect of time on dialysis and renal transplantation on endothelial function: a
      longitudinal analysis.
AB  - BACKGROUND: Soluble vascular cell adhesion molecule-1 (sVCAM-1) is a marker of
      endothelial injury and a potent predictor of cardiovascular mortality in patients
      with kidney failure on dialysis. The longitudinal effects of dialysis on
      endothelial dysfunction and in particular the effects of renal transplantation on
      markers of endothelial function including sVCAM-1 have not been well
      characterized. METHODS: We used the Transplant Manitoba registry and biobank to
      assemble a retrospective cohort of all patients receiving a first kidney
      transplant between January 1, 2000, and December 31, 2005 (n=186). One hundred
      seventy-four patients had at least two serum samples pretransplant and at least
      two samples posttransplant. In total, 1,004 serial samples (median 5/patient)
      were analyzed. Factors associated with sVCAM-1 were examined using mixed linear
      models. RESULTS: The sVCAM-1 levels increased progressively on dialysis (0.15
      [0.10 to 0.20] ng/mL/day; P<0.0001), fell significantly within 1 month after
      transplantation (-625 ng/mL/day; P<0.0001) and continued to fall thereafter (
      0.23 [-0.34 to -0.12] ng/mL/day). Smoking and heart failure were associated with
      higher sVCAM-1 levels, whereas transplantation was associated with lower sVCAM-1
      levels. The relationship between sVCAM-1 and transplantation was not changed by
      multivariate adjustment. CONCLUSION: Endothelial injury worsens over time on
      dialysis but improves significantly after renal transplantation.

PMID- 24879383
TI  - Bronchoalveolar lavage lateral-flow device test for invasive pulmonary
      aspergillosis in solid organ transplant patients: a semiprospective multicenter
      study.
AB  - BACKGROUND: Invasive pulmonary aspergillosis (IPA) remains an important cause of
      morbidity and mortality among patients undergoing solid organ transplantation
      (SOT). Because of the crude mortality of 80% to 90% in the absence of adequate
      treatment, timely diagnosis and early intervention with antifungal drugs are key
      factors in the successful treatment of IPA. Diagnosis, however, remains
      difficult. Therefore, new diagnostic tests are urgently needed. The Lateral-Flow
      Device (LFD) test is a rapid (15 min) single-sample point-of-care test that is
      based on the detection of an Aspergillus extracellular glycoprotein antigen by
      monoclonal antibody JF5. METHODS: This semiprospective multicenter study
      evaluated the LFD test for IPA diagnosis (established by galactomannan and
      culture results) by using bronchoalveolar lavage (BAL) samples from patients
      after SOT. Participating centers were the three Austrian Medical Universities of
      Innsbruck, Vienna, and Graz. RESULTS: Forty-seven BAL samples from 47 SOT
      patients were included (26 patients had undergone lung transplantation, 13 liver,
      6 kidney, and 2 heart transplantation; 11 probable or proven IPA, 11 possible
      IPA, 25 no IPA) at the three Austrian Medical Universities of Innsbruck, Vienna,
      and Graz. Sensitivity and specificity, positive and negative predictive values,
      as well as diagnostic odds ratio of BAL LFD tests for probable IPA were 91%, 83%,
      63%, 97%, and 50% (95% confidence interval, 5.4%-467%), respectively. CONCLUSION:
      To conclude, the LFD test of BAL specimens is performed easily and provides
      accurate and rapidly available results in patients after SOT. Therefore, this new
      point-of-care test may be a promising diagnostic approach for detecting IPA using
      BAL specimens from SOT patients.

PMID- 24879384
TI  - De novo donor-specific human leukocyte antigen antibodies early after kidney
      transplantation.
AB  - BACKGROUND: Our aim was to determine the incidence of de novo donor-specific
      human leukocyte antigen (HLA) antibody (dnDSA) during the first year after kidney
      transplantation and the impact of early dnDSA on acute rejection and protocol
      biopsy findings. METHODS: We selected all patients who received a kidney
      transplant at our center between July 2010 and March 2012. Single antigen bead
      assay was performed at 1, 4 and 12 months after transplantation. Only DSAs with a
      mean fluorescence intensity (MFI) of greater 999 were included. RESULTS: We
      included 245 kidney transplant recipients who did not have a DSA before
      transplantation. At 12 months, 8.2% of the patients developed dnDSA; 2.4% of them
      were to HLA class I and 6.5% to HLA class II. Of the 32 patients with a dnDSA at
      1 or 4 months, only 8 (25%) persisted at 12 months. The risk of antibody-mediated
      rejection (AMR) was higher in the dnDSA group. For the dnDSA group with MFI of
      3,000 or greater (compared with the group with MFI<3,000), the hazard ratio for
      AMR was 10.6 (95% confidence interval, 2.27-49.5). The cumulative incidence of
      AMR or mixed rejection at 1 year was 30% in the group with dnDSA MFI level of
      3,000 or greater but only 4% for the group with dnDSA with MFI less than 3,000.
      On 1-year protocol biopsies, the dnDSA group showed more interstitial
      inflammation, tubulitis, and glomerulitis. CONCLUSION: We conclude that dnDSA
      occurring during the first posttransplantation year may be transient, and the
      risk of AMR is higher in patients with a dnDSA MFI level that is greater than
      3,000.

PMID- 24879385
TI  - A pilot program to evaluate deceased donor disease transmission risk: the New
      York Organ Donor Network Infectious Disease Working Group.
AB  - BACKGROUND: Recent cases of donor-derived infections raise the question of how
      best to screen donors without excessive restriction of the donor pool. METHODS:
      The New York Organ Donor Network (NYODN) established an Infectious Diseases
      Working Group (IDWG) in 2008, which established an on-call schedule of voluntary
      transplant infectious disease physicians to provide remote evaluations for donors
      at increased risk for disease transmission. RESULTS: Data were reviewed from 40
      available IDWG evaluations from 2008 to 2011. Eighteen cases (45%) were
      considered to be at unacceptable risk for infection transmission. Sixteen of
      these cases were excluded from donation secondary to IDWG recommendation; there
      was limited recipient center interest in the remaining two cases. Approximately
      22 (55%) cases were categorized by the IDWG as acceptable, with 14 proceeding to
      recovery of 49 organs. IDWG physician recommendations were conveyed to recipient
      centers, and screening guidelines for donors were revised based on the IDWG
      experiences. CONCLUSION: Establishment of a donation service area disease
      transmission evaluation service is a valuable program for donor screening and may
      promote dissemination of more detailed donor information to recipient centers.

PMID- 24879386
TI  - Pretransplantation recipient regulatory T cell suppressive function predicts
      delayed and slow graft function after kidney transplantation.
AB  - BACKGROUND: Delayed graft function (DGF) and slow graft function (SGF) are a
      continuous spectrum of ischemia-reperfusion-related acute kidney injury (AKI)
      that increases the risk for acute rejection and graft loss after kidney
      transplantation. Regulatory T cells (Tregs) are critical in transplant tolerance
      and attenuate murine AKI. In this prospective observational cohort study, we
      evaluated whether pretransplantation peripheral blood recipient Treg frequency
      and suppressive function are predictors of DGF and SGF after kidney
      transplantation. METHODS: Deceased donor kidney transplant recipients (n=53) were
      divided into AKI (n=37; DGF, n=10; SGF, n=27) and immediate graft function (n=16)
      groups. Pretransplantation peripheral blood CD4CD25FoxP3 Treg frequency was
      quantified by flow cytometry. Regulatory T-cell suppressive function was measured
      by suppression of autologous effector T-cell proliferation by Treg in co-culture.
      RESULTS: Pretransplantation Treg suppressive function, but not frequency, was
      decreased in AKI recipients (P<0.01). In univariate and multivariate analyses
      accounting for the effects of cold ischemic time and donor age, Treg suppressive
      function discriminated DGF from immediate graft function recipients in
      multinomial logistic regression (odds ratio, 0.77; P<0.01), accurately predicted
      AKI in receiver operating characteristic curve (area under the curve, 0.82;
      P<0.01), and predicted 14-day estimated glomerular filtration rate in linear
      regression (P<0.01). CONCLUSION: Our results indicate that recipient peripheral
      blood Treg suppressive function is a potential independent pretransplantation
      predictor of DGF and SGF.

PMID- 24879388
TI  - Glucagon responses to increasing oral loads of glucose and corresponding
      isoglycaemic intravenous glucose infusions in patients with type 2 diabetes and
      healthy individuals.
AB  - AIMS/HYPOTHESIS: Type 2 diabetes is associated with hypersecretion of glucagon
      during an OGTT, whereas i.v. glucose suppresses glucagon levels. This suggests
      that type 2 diabetic hyperglucagonaemia may result from glucose stimulation of
      the gastrointestinal tract. We evaluated glucagon responses to increasing amounts
      of glucose given orally and corresponding isoglycaemic i.v. glucose infusions
      (IIGIs) in patients with type 2 diabetes and in healthy controls. METHODS: Plasma
      glucagon responses were measured during three 4 h OGTTs with increasing loads of
      glucose (25 g, 75 g and 125 g) and three corresponding IIGIs in eight patients
      with type 2 diabetes (age [mean +/- SEM] 57 +/- 4 years; BMI 29.5 +/- 1.0
      kg/m(2); HbA1c 7.0 +/- 0.3% [53 +/- 2 mmol/mol]) and eight healthy individuals
      (age 57 +/- 4 years; BMI 28.9 +/- 0.7 kg/m(2); HbA1c 5.4 +/- 0.1% [36 +/- 1
      mmol/mol]). RESULTS: In healthy controls no difference in glucagon suppression
      during the first 45 min of the 25 g OGTT and the corresponding IIGI (-153 +/- 35
      vs -133 +/- 24 min * pmol/l; p = NS) was observed, whereas patients with type 2
      diabetes only exhibited significant glucagon suppression following IIGI (29 +/-
      27 vs -144 +/- 20 min * pmol/l; p = 0.005). At higher oral glucose loads this
      difference increased and also became evident in healthy controls.
      CONCLUSIONS/INTERPRETATION: In patients with type 2 diabetes increasing amounts
      of oral glucose elicit hypersecretion of glucagon, whereas corresponding IIGIs
      result in significant glucagon suppression; a phenomenon that is also observed in
      healthy individuals when larger glucose loads are ingested orally. This suggests
      that the hyperglucagonaemic response to oral glucose in type 2 diabetes may
      represent a pathological version of a gut-derived physiological phenomenon. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT00529048.

PMID- 24879387
TI  - Physiologic changes associated with cerebellar dystonia.
AB  - Dystonia is a neurologic disorder characterized by sustained involuntary muscle
      contractions. Lesions responsible for unilateral secondary dystonia are confined
      to the putamen, caudate, globus pallidus, and thalamus. Dysfunction of these
      structures is suspected to play a role in both primary and secondary dystonia.
      Recent evidence has suggested that the cerebellum may play a role in the
      pathophysiology of dystonia. The role of the cerebellum in ataxia, a disorder of
      motor incoordination is well established. How may the cerebellum contribute to
      two apparently very different movement disorders? This review will discuss the
      idea of whether in some cases, ataxia and dystonia lie in the same clinical
      spectrum and whether graded perturbations in cerebellar function may explain a
      similar causative role for the cerebellum in these two different motor disorders.
      The review also proposes a model for cerebellar dystonia based on the available
      animal models of this disorder. 

PMID- 24879389
TI  - Phosphate analogues in the dissection of mechanism.
AB  - Phosphoryl group transfer is central to genetic replication, cellular signalling
      and many metabolic processes. Understanding the mechanisms of phosphorylation and
      phosphate ester and anhydride cleavage is key to efforts towards biotechnological
      and biomedical exploitation of phosphate-handling enzymes. Analogues of phosphate
      esters and anhydrides are indispensable tools, alongside protein mutagenesis and
      computational methods, for the dissection of phosphoryl transfer mechanisms.
      Hydrolysable and non-hydrolysable phosphate analogues have provided insight into
      the nature and sites of phosphoryl transfer processes. Kinetic isotope effects
      and crystallography using transition state analogues have painted more detailed
      pictures of transition states and how enzymes work to stabilise them. 

PMID- 24879390
TI  - Health behaviors and needs of melanoma survivors.
AB  - PURPOSE: Little is known about melanoma survivors' long-term symptoms, sun
      protection practices, and support needs from health providers. METHODS: Melanoma
      survivors treated at Stanford Cancer Center from 1995 through 2011 were invited
      to complete a heath needs survey. We compared responses of survivors by sex,
      education, time since diagnosis (long-term vs. short-term survivors), and extent
      of treatment received (wide local excision (WLE) alone versus WLE plus additional
      surgical or medical treatment (WLE+)). RESULTS: One hundred sixty melanoma
      survivors (51 % male; 61 % long-term; 73 % WLE+) provided evaluable data. On
      average, patients were 62 years of age (SD = 14), highly educated (75 % college
      degree), and Caucasian (94 %). Overall, participants rated anxiety as the most
      prevalent symptom (34 %). Seventy percent reported that their health provider did
      not address their symptoms, and 53 % requested education about melanoma-specific
      issues. Following treatment, women spent significantly less time seeking a tan
      compared with men (p = 0.01), had more extremity swelling (p = 0.014), and
      expressed higher need for additional services (p = 0.03). Long-term survivors
      decreased their use of tanning beds (p = 0.03) and time spent seeking a tan (p =
      0.002) and were less likely to receive skin screening every 3-6 months (p <
      0.001) compared with short-term survivors. WLE+ survivors reported greater
      physical long-term effects than WLE survivors (p <= 0.001) following treatment.
      CONCLUSIONS: Melanoma survivors experience continuing symptoms long after
      treatment, namely anxiety, and they express a need for information about long
      term melanoma effects, psychosocial support, and prevention of further skin
      cancer.

PMID- 24879392
TI  - Prediction of temperature and damage in an irradiated human eye-Utilization of a
      detailed computer model which includes a vectorial blood stream in the choroid.
AB  - The work presented here describes the development and use of a three-dimensional
      thermo-dynamic model of the human eye for the prediction of temperatures and
      damage thresholds under irradiation. This model takes into account the blood flow
      by the implementation of a vectorial blood stream in the choroid and also uses
      the actual physiological extensions and tissue parameters of the eye. Furthermore
      it considers evaporation, radiation and convection at the cornea as well as the
      eye lid. The predicted temperatures were successfully validated against existing
      eye models in terms of corneal and global thermal behaviour. The model's
      predictions were additionally checked for consistency with in-vivo temperature
      measurements of the cornea, the irradiated retina and its damage thresholds.
      These thresholds were calculated from the retinal temperatures using the
      Arrhenius integral. Hence the model can be used to predict the temperature
      increase and irradiation hazard within the human eye as long as the absorption
      values and the Arrhenius coefficients are known and the damage mechanism is in
      the thermal regime. 

PMID- 24879393
TI  - Evaluation of a streamlined model of care for minor burn patients.
AB  - Minor burns represent the majority of all burn patients in developed countries,
      yet little information regarding their outcomes is available in the literature.
      Minor burns at Royal Perth Hospital are provided routine outpatient clinic follow
      up at 1 month postinjury resulting in increased ambulatory care demand and
      inefficiency due to high failure to attend rates. The authors hypothesized that
      improving patient education and using a posted quality-of-life survey in place of
      a 1-month outpatient clinic follow-up visit for minor burn patients would improve
      efficiency without compromising outcome compared to current standard practice. A
      sample of conservatively managed minor burn outpatients who healed within 14 days
      were administered a burn care education manual and discharged. Participants were
      assessed using postal Burn-Specific Health Scale-Brief and satisfaction surveys
      at 1 month postburn. Their responses were compared to those of patients who had
      received standard care. The intervention group had a higher, but not
      statistically significant, median BSHS-B score (156) than the comparison group
      (153) (P =.05). The intervention group also reported high levels of satisfaction
      with service. The new model of care is an appropriate strategy for management of
      minor burn. Its benefit over current hospital-based follow-up is that it saves
      one clinic appointment, improves efficiency related to nonattendance, and reduces
      patient burden. 

PMID- 24879394
TI  - Clinical guidelines in the management of burn injury: a review and
      recommendations from the organization and delivery of burn care committee.

PMID- 24879391
TI  - Management options for established chemotherapy-induced peripheral neuropathy.
AB  - Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating
      condition associated with a variety of chemotherapeutic agents. Clinicians are
      cognizant of the negative impact of CIPN on cancer treatment outcomes and
      patients' psychosocial functioning and quality of life. In an attempt to
      alleviate this problem, clinicians and patients try various therapeutic
      interventions, despite limited evidence to support efficacy of these treatments.
      The rationale for such use is mostly based on the evidence for the treatment
      options in non-CIPN peripheral neuropathy syndromes, as this area is more
      robustly studied than is CIPN treatment. In this manuscript, we examine the
      existing evidence for both CIPN and non-CIPN treatments and develop a summary of
      the best available evidence with the aim of developing a practical approach to
      the treatment of CIPN, based on available literature and clinical practice
      experience. 

PMID- 24879395
TI  - Coverage of chest wall defect in a case of electric burns by pedicled omental
      flap.
AB  - Electrical burns can be devastating and result in dreaded outcomes. Electrical
      burn is a common problem in our society and needs special attention because of
      its various modes of presentations, the numbers of organ systems involved, and
      the mortality associated in spite of the small percent of burns. The authors
      present a case of electrical burns with a posterolateral chest wall defect
      associated with blunt abdominal trauma that was successfully managed by
      debridement and pedicled omental flap over a synthetic prolene mesh. 

PMID- 24879396
TI  - The first reported case of ureteral perforation in a patient with severe toxic
      epidermal necrolysis syndrome.
AB  - The aim of this study was to briefly review toxic epidermal necrolysis syndrome
      (TENS) and Steven Johnson Syndrome (SJS), as well as describe the unique
      complication of ureteral perforation. A case of ureteral perforation in an 18
      year old woman with TENS was documented and reviewed. In addition to studying
      this unusual presentation the authors have also provided a brief review of TENS
      and SJS along with several common complications of this disease process. The
      patient in question suffered a severe case of TENS with extensive mucocutaneous
      involvement. After 2 weeks of intensive therapy, she suddenly became anuric. She
      developed obstructive uropathy and bilateral hydronephrosis from mucosal debris
      and sludge. A left forniceal rupture was visualized on pyelography. SJS and TENS
      are two different presentations in the spectrum of the same disease process.
      There have been descriptions of gastrointestinal, respiratory, vaginal, and
      ocular mucosal involvement, including cases of corneal and colonic perforation.
      However, acute renal failure secondary to ureteral obstruction and perforation
      has never been described. Although rare, one must entertain every possibility
      when attempting to diagnose complications of the disease. 

PMID- 24879397
TI  - Enteral nutrition intolerance in critically ill septic burn patients.
AB  - The purpose of this study was to investigate the frequency of enteral feeding
      intolerance in critically ill septic burn patients, the effect of enteral feeding
      intolerance on the efficacy of feeding, the correlation between the infection
      marker (procalcitonin [PCT]) and the nutrition status marker (prealbumin) and the
      impact of feeding intolerance on the outcome of septic burn patients. From
      January 2009 to December 2012 the data of all burn patients with the diagnosis of
      sepsis who were placed on enteral nutrition were analyzed. Septic patients were
      divided into two groups: group A, septic patients who developed feeding
      intolerance; group B, septic patients who did not develop feeding intolerance.
      Demographic and clinical characteristics of patients were analyzed and compared.
      The diagnosis of sepsis was applied to 29% of all patients. Of these patients 35%
      developed intolerance to enteral feeding throughout the septic period. A
      statistically significant increase in mean PCT level and a decrease in prealbumin
      level was observed during the sepsis period. Group A patients had statistically
      significant lower mean caloric intake, higher PCT:prealbumin ratio, higher
      pneumonia incidence, higher Sequential Organ Failure Assessment Maximum Score, a
      longer duration of mechanical ventilation, and a higher mortality rate in
      comparison with the septic patients without gastric feeding intolerance. The
      authors concluded that a high percentage of septic burn patients developed
      enteral feeding intolerance. Enteral feeding intolerance seems to have a negative
      impact on the patients' nutritional status, morbidity, and mortality. 

PMID- 24879399
TI  - Parsonage-Turner syndrome in second-degree contact burns.
AB  - Literature on the complications of burns is abundant. However, there is a paucity
      of literature on Parsonage-Turner syndrome as a complication of contact burns.
      The authors described the case of a 27-year-old Chinese man who sustained contact
      burns on the left upper limb and the left side of the chest wall, presenting
      sharp intense pain and swelling of the left shoulder deriving from the diagnosis
      of Parsonage-Turner syndrome. On the basis of clinical findings, the authors
      selected conservative treatment both for the burns and brachial plexus injury.
      Approximately 10 days postinjury the patient was able to move his upper limb in
      the same range as the contralateral uninjured limb. The sensory function
      recovered and the numbness of the upper limb gradually disappeared. This case
      shows that Parsonage-Turner syndrome can occur even in second-degree burns with a
      small total body surface area. Therefore, careful physical examination, early
      recognition, and prompt treatment are essential for recovery of the injured limb.

PMID- 24879398
TI  - Activities of nonlysosomal proteolytic systems in skeletal and cardiac muscle
      during burn-induced hypermetabolism.
AB  - The aim of this study was to assess the activity of nonlysosomal proteolytic
      systems in skeletal and cardiac muscle during burn-induced hypermetabolism (BHM)
      in rats. Rats underwent 30% TBSA scald burn or sham injury and were observed for
      up to 42 days. Body weights and resting energy expenditures were determined
      weekly. Skeletal (soleus/pectoral) muscle and hearts were harvested on days 0
      (=control), 7, 14, 21, and 42 after burn. Calpain, caspase-1, caspase-3/7,
      caspase-6, caspase-8, caspase-9, and proteasome peptidase activities were
      measured in tissue extracts. Hypermetabolism developed within 3 weeks after
      burns, as documented by increased resting energy expenditures and decreased body
      weights on postburn days 21 to 42 (P < 0.05 vs control). Calpain activities did
      not show significant alterations. Pan caspase activities increased by time and
      were significantly increased in skeletal and cardiac muscle extracts during
      hypermetabolism. Although increases in caspase-1, caspase-8, and caspase-9
      activities were predominantly responsible for elevated pan caspase activities in
      skeletal muscle, increases in caspase-6 activities dominated in the heart.
      Proteasome peptidase activities in skeletal muscle extracts were not
      significantly altered. Proteasome peptidase activities in heart extracts
      increased time dependently and were significantly increased during BHM.
      Activation of caspase cascades during BHM constitutes a uniform response in
      skeletal and cardiac muscle and may contribute to enhanced metabolic protein
      turnover. Activation of myocardial proteasome activities may reflect persistent
      cardiac stress. Further exploration of caspase cascades and the proteasome as
      therapeutic targets to influence long-term consequences of BHM appears justified.

PMID- 24879400
TI  - A promoter analysis of MOTHER OF FT AND TFL1 1 (JcMFT1), a seed-preferential gene
      from the biofuel plant Jatropha curcas.
AB  - MOTHER OF FT AND TFL1 (MFT)-like genes belong to the phosphatidylethanoamine
      binding protein (PEBP) gene family in plants. In contrast to their homologs
      FLOWERING LOCUS T (FT)-like and TERMINAL FLOWER 1 (TFL1)-like genes, which are
      involved in the regulation of the flowering time pathway, MFT-like genes function
      mainly during seed development and germination. In this study, a full-length cDNA
      of the MFT-like gene JcMFT1 from the biodiesel plant Jatropha curcas (L.) was
      isolated and found to be highly expressed in seeds. The promoter of JcMFT1 was
      cloned and characterized in transgenic Arabidopsis. A histochemical beta
      glucuronidase (GUS) assay indicated that the JcMFT1 promoter was predominantly
      expressed in both embryos and endosperms of transgenic Arabidopsis seeds.
      Fluorometric GUS analysis revealed that the JcMFT1 promoter was highly active at
      the mid to late stages of seed development. After seed germination, the JcMFT1
      promoter activity decreased gradually. In addition, both the JcMFT1 expression in
      germinating Jatropha embryos and its promoter activity in germinating Arabidopsis
      embryos were induced by abscisic acid (ABA), possibly due to two ABA-responsive
      elements, a G-box and an RY repeat, in the JcMFT1 promoter region. These results
      show that the JcMFT1 promoter is seed-preferential and can be used to control
      transgene expression in the seeds of Jatropha and other transgenic plants.

PMID- 24879401
TI  - How do sink and source activities influence the reproduction and vegetative
      growth of spring ephemeral herbs under different light conditions?
AB  - Spring ephemeral herbs inhabiting deciduous forests commonly complete
      reproduction and vegetative growth before canopy closure in early summer. Effects
      of shading by early canopy closure on reproductive output and vegetative growth,
      however, may vary depending on the seasonal allocation patterns of photosynthetic
      products between current reproduction and storage for future growth in each
      species. To clarify the effects of sink-source balance on seed production and
      bulb growth in a spring ephemeral herb, Gagea lutea, we performed a bract removal
      treatment (source reduction) and a floral-bud removal treatment (sink reduction)
      under canopy and open conditions. Leaf carbon fixations did not differ between
      the forest and open sites and among treatments. Bract carbon fixations were also
      similar between sites but tended to decrease when floral buds were removed. Seed
      production was higher under open condition but decreased by the bract-removal
      treatment under both light conditions. In contrast, bulb growth was independent
      of light conditions and the bract-removal treatment but increased greatly by the
      bud-removal treatment. Therefore, leaves and bracts acted as specialized source
      organs for vegetative and reproductive functions, respectively, but
      photosynthetic products by bracts were flexibly used for bulb growth when plants
      failed to set fruits. Extension of bright period was advantageous for seed
      production (i.e., source limited) but not for vegetative growth (i.e., sink
      limited) in this species. 

PMID- 24879402
TI  - The impact of directed choice on the design of preventive healthcare facility
      network under congestion.
AB  - Preventive healthcare (PH) programs and services aim at reducing the likelihood
      and severity of potentially life-threatening illness by early detection and
      prevention. The effectiveness of these programs depends on the participation
      level and the accessibility of the users to the facilities providing the
      services. Factors that impact the accessibility include the number, type, and
      location of the facilities as well as the assignment of the clients to these
      facilities. In this paper, we study the impact of system-optimal (i.e., directed)
      choice on the design of the preventive healthcare facility network under
      congestion. We present a model that simultaneously determines the location and
      the size of the facilities as well as the allocation of clients to these
      facilities so as to minimize the weighted sum of the total travel time and the
      congestion associated with waiting and service delay at the facilities. The
      problem is set up as a network of spatially distributed M/G/1 queues and
      formulated as a nonlinear mixed integer program. Using simple transformation of
      the nonlinear objective function and piecewise linear approximation, we
      reformulate the problem as a linear model. We present a cutting plane algorithm
      based exact (??-optimal) solution approach. We analyze the tradeoff between
      travel time and queuing time and its impact on the location and capacity of the
      facilities as well as the allocation of clients to these facilities under a
      directed choice policy. We present a case study that deals with locating
      mammography clinics in Montreal, Canada. The results show that incorporating
      congestion in the PH facility network design substantially reduces the total time
      spent by clients. The proposed model allows policy makers to direct clients to
      facilities in an equitable manner resulting in better accessibility. 

PMID- 24879403
TI  - A network flow approach for tactical resource planning in outpatient clinics.
AB  - This paper introduces a deterministic model to plan the physician requirements
      for outpatient clinics to achieve service targets for the appointment lead-times
      of patients. The Ministry of Health of Singapore has established targets for the
      median, 95th percentile, and 100th percentile of appointment lead-times for
      patients, since long appointment postponements are regarded as being unacceptable
      for health care services. The study is to match the capacity of the healthcare
      providers to the patient demand for a re-entry system, subject to restrictions on
      the appointment lead-times for patients. We propose a mixed-integer programming
      model for planning capacity with the minimization of the maximum required
      capacity as its objective. In the model we assume a finite planning horizon,
      deterministic arrivals, multiple types of patients, identical physicians, and
      dependent demand between types of patients. We solve this model with a Branch and
      Cut algorithm. We test the model with numerical experiments using real data from
      the chosen specialty at the outpatient clinic of the studied hospital. The
      results show the value of the proposed model via a systematic push-pull mechanism
      in scheduling patients' requests to minimize the objective. The clinic should use
      one of the appointment lead-time targets to determine the patients' appointment
      dates. Finally, from the sensitivity analyses we demonstrate that the objective
      is negatively correlated with first-visit patients' appointment lead-time
      targets, the discharge rates, and the re-visit patients' mean appointment lead
      time; we find a positive correlation between the first-visit patients' mean
      appointment lead-time and the appointment lead-time targets. 

PMID- 24879404
TI  - Laparoscopic versus open partial nephrectomy for clinical T1 renal masses: no
      impact of surgical approach on perioperative complications and long-term
      postoperative quality of life.
AB  - OBJECTIVES: Beyond oncological safety, consideration of 30-day complications
      according to Clavien-Dindo, as well as postoperative quality of life (QoL) after
      nephron-sparing surgery for clinical T1 renal masses, represents important
      factors for treatment decision counseling. The objective of this study was to
      compare the effect of laparoscopic versus open partial nephrectomy (LPN vs. OPN)
      on 30-day complications and long-term postoperative QoL for clinical T1 renal
      masses. METHODS: Retrospective, longitudinal analysis of 293 patients treated
      with either LPN versus OPN for T1 renal masses. The investigated endpoints were
      30-day Clavien-Dindo complications and health-related QoL (EORTC QLQ-C30).
      Respectively, logistic and linear regression models analyzed the effect of
      surgical partial nephrectomy approach on endpoints. RESULTS: Overall complication
      rates were similar in patients undergoing OPN or LPN (16.1 vs. 14.6 %, p = 0.8).
      Significantly less major complications (2.4 vs. 10.4 %, p = 0.025) occurred after
      LPN. Despite a shorter convalescence period for LPN patients (p = 0.035), in uni-
      and multivariable analyses, surgical approach was not associated with 30-day
      complications nor long-term differences in QoL (all p > 0.05). CONCLUSIONS:
      Despite a faster recovery time after LPN, our findings suggest that LPN and OPN
      are equivalent with regard to 30-day Clavien-Dindo complication rates and long
      term QoL.

PMID- 24879405
TI  - Outcomes of minimally invasive simple prostatectomy for benign prostatic
      hyperplasia: a systematic review and meta-analysis.
AB  - PURPOSE: (1) To assess the outcomes of minimally invasive simple prostatectomy
      (MISP) for the treatment of symptomatic benign prostatic hyperplasia in men with
      large prostates and (2) to compare them with open simple prostatectomy (OSP).
      METHODS: A systematic review of outcomes of MISP for benign prostatic hyperplasia
      with meta-analysis was conducted. The article selection process was conducted
      according to the PRISMA guidelines. RESULTS: Twenty-seven observational studies
      with 764 patients were analyzed. The mean prostate volume was 113.5 ml (95 % CI
      106-121). The mean increase in Qmax was 14.3 ml/s (95 % CI 13.1-15.6), and the
      mean improvement in IPSS was 17.2 (95 % CI 15.2-19.2). Mean duration of operation
      was 141 min (95 % CI 124-159), and the mean intraoperative blood loss was 284 ml
      (95 % CI 243-325). One hundred and four patients (13.6 %) developed a surgical
      complication. In comparative studies, length of hospital stay (WMD -1.6 days, p =
      0.02), length of catheter use (WMD -1.3 days, p = 0.04) and estimated blood loss
      (WMD -187 ml, p = 0.015) were significantly lower in the MISP group, while the
      duration of operation was longer than in OSP (WMD 37.8 min, p < 0.0001). There
      were no differences in improvements in Qmax, IPSS and perioperative complications
      between both procedures. The small study sizes, publication bias, lack of
      systematic complication reporting and short follow-up are limitations.
      CONCLUSIONS: MISP seems an effective and safe treatment option. It provides
      similar improvements in Qmax and IPSS as OSP. Despite taking longer, it results
      in less blood loss and shorter hospital stay. Prospective randomized studies
      comparing OSP, MISP and laser enucleation are needed to define the standard
      surgical treatment for large prostates.

PMID- 24879406
TI  - Colonoscopic evaluation in ulcerative colitis.
AB  - Colonoscopic evaluation is an important tool in the evaluation of ulcerative
      colitis (UC). UC is divided by disease extent into proctitis, proctosigmoiditis,
      left-sided colitis, and pan-colitis. In addition, a cecal or peri-appendiceal
      patch and backwash ileitis are associated with UC. The extent and behavior of UC
      has been characterized further using various indices and scoring systems; among
      these systems is the Mayo Score, which is widely used in current clinical trials
      for new medications. As these medical therapies for UC have developed, achieving
      mucosal healing with medications has become an important therapeutic objective. 

PMID- 24879409
TI  - Susceptibility-weighted imaging for the noncontrast evaluation of hepatocellular
      carcinoma: a prospective study with histopathologic correlation.
AB  - BACKGROUND: Specific morphologic features of hepatocellular carcinoma (HCC) on
      imaging have identifiable pathologic correlates as well as implications for
      altering surgical management and defining prognosis. In this study, we compared
      susceptibility-weighted imaging (SWI) to conventional techniques and correlated
      our findings with histopathology to determine the role of SWI in assessing
      morphologic features of HCC without using a contrast agent. METHODS: 86
      consecutive patients with suspected HCC were imaged with MRI (including T1, T2,
      T2*, and SWI) and subsequently CT. 59 histologically-proven HCC lesions were
      identified in 53 patients. Each lesion on each imaging sequence was evaluated by
      two radiologists, and classified with respect to lesion morphology, signal
      intensity relative to surrounding hepatic parenchyma, presence of a
      pseudocapsule, presence of venous invasion, and internal homogeneity. RESULTS:
      Histopathology confirmed pseudocapsules in 41/59 lesions. SWI was able to detect
      a pseudocapsule in 34/41 lesions; compared to conventional T1/T2 imaging (12/41)
      and T2* (27/41). Mosaic pattern was identified in 25/59 lesions by
      histopathology; SWI confirmed this in all 25 lesions, compared to T1/T2 imaging
      (13/25) or T2* (18/25). Hemorrhage was confirmed by histopathology in 43/59
      lesions, and visible on SWI in 41/43 lesions, compared to T1/T2 (7/43) and T2*
      (38/43). Venous invasion was confirmed by histopathology in 31/59 patients; SWI
      demonstrated invasion in 28/31 patients, compared to T1/T2 (7/31) and T2*
      (24/31). CONCLUSIONS: SWI is better at identifying certain morphologic features
      such as pseudocapsule and hemorrhage than conventional MRI without using a
      contrast agent in HCC patients.

PMID- 24879410
TI  - Revealing time-unlocked brain activity from MEG measurements by common waveform
      estimation.
AB  - Brain activities related to cognitive functions, such as attention, occur with
      unknown and variable delays after stimulus onsets. Recently, we proposed a method
      (Common Waveform Estimation, CWE) that could extract such brain activities from
      magnetoencephalography (MEG) or electroencephalography (EEG) measurements. CWE
      estimates spatiotemporal MEG/EEG patterns occurring with unknown and variable
      delays, referred to here as unlocked waveforms, without hypotheses about their
      shapes. The purpose of this study is to demonstrate the usefulness of CWE for
      cognitive neuroscience. For this purpose, we show procedures to estimate unlocked
      waveforms using CWE and to examine their role. We applied CWE to the MEG epochs
      during Go trials of a visual Go/NoGo task. This revealed unlocked waveforms with
      interesting properties, specifically large alpha oscillations around the temporal
      areas. To examine the role of the unlocked waveform, we attempted to estimate the
      strength of the brain activity of the unlocked waveform in various conditions. We
      made a spatial filter to extract the component reflecting the brain activity of
      the unlocked waveform, applied this spatial filter to MEG data under different
      conditions (a passive viewing, a simple reaction time, and Go/NoGo tasks), and
      calculated the powers of the extracted components. Comparing the powers across
      these conditions suggests that the unlocked waveforms may reflect the inhibition
      of the task-irrelevant activities in the temporal regions while the subject
      attends to the visual stimulus. Our results demonstrate that CWE is a potential
      tool for revealing new findings of cognitive brain functions without any
      hypothesis in advance. 

PMID- 24879413
TI  - The nanocomposite of polyaniline and nitrogen-doped layered HTiNbO5 with
      excellent visible-light photocatalytic performance.
AB  - An effective approach has been used to synthesize N-doped HTiNbO5 (denoted as N
      HTiNbO5) with a better intercalation property. The synthesis of polyaniline
      (PANI) with N-HTiNbO5 to form PANI-N-HTiNbO5 lamellar nanocomposites by in situ
      polymerization using the aniline (ANI) intercalation compound ANI/N-HTiNbO5 as
      the intermediate has been investigated. The resulting PANI-N-HTiNbO5
      nanocomposite showed a better crystallinity with a monolayer of PANI within the
      interlayers of N-HTiNbO5, because nitrogen doping can affect the surface charge
      distribution of [TiNbO5](-) layers. The cyclic voltammetry (CV) results indicated
      that the PANI-N-HTiNbO5 nanocomposite had good redox activity and electrochemical
      cycling stability in acidic solution. The visible-light response of the PANI-N
      HTiNbO5 nanocomposite was enhanced through N-doping, acid exchange, and the
      intercalation of PANI. The PANI-N-HTiNbO5 nanocomposite showed the highest
      activity with 97.8% methylene blue (MB) photodegraded in 170 min under visible
      light irradiation. The significant enhancement of photocatalytic performance can
      be attributed to the high efficiency of charge separation, induced by the
      synergistic effect between PANI and N-HTiNbO5. In addition, the PANI-N-HTiNbO5
      nanocomposite had a high thermal and photodegradation stability due to the
      intercalation reaction at the molecular level. 

PMID- 24879411
TI  - Prohibitin expression deregulation in gastric cancer is associated with the 3'
      untranslated region 1630 C>T polymorphism and copy number variation.
AB  - PHB is a reported oncogene and tumor suppressor in gastric cancer. Here, we
      evaluated whether the PHB copy number and the rs6917 polymorphism affect its
      expression in gastric cancer. Down-regulation and up-regulation of PHB were
      observed in the evaluated tumors. Reduced expression was associated with tumor
      dedifferentiation and cancer initiation. The T allele of the rs6917 polymorphism
      was associated with reduced PHB mRNA levels. Moreover, the up-regulation of PHB
      appeared to be regulated by the gain of additional gene copies. Thus, PHB copy
      number variation and differential expression of the rs6917 polymorphism may play
      a role in PHB transcriptional regulation. 

PMID- 24879412
TI  - Not just playing around: infants' behaviors with objects reflect ability,
      constraints, and object properties.
AB  - This study describes infants' behaviors with objects in relation to age, body
      position, and object properties. Object behaviors were assessed longitudinally in
      22 healthy infants supine, prone, and sitting from birth through 2 years. Results
      reveal: (1) infants learn to become intense and sophisticated explorers within
      the first 6 months of life; (2) young infants dynamically and rapidly shift among
      a variety of behavioral combinations to gather information; (3) behaviors on
      objects develop along different trajectories so that behavioral profiles vary
      across time; (4) object behaviors are generally similar in supine and sitting but
      diminished in prone; and (5) infants begin matching certain behaviors to object
      properties as newborns. These data demonstrate how infants learn to match their
      emerging behaviors with changing positional constraints and object affordances.

PMID- 24879414
TI  - Lysophosphatidic acid enhanced the angiogenic capability of human chondrocytes by
      regulating Gi/NF-kB-dependent angiogenic factor expression.
AB  - Lysophosphatidic acid (LPA) has been found to mediate myeloid differentiation,
      stimulate osteogenesis, alter cell proliferation and migration, and inhibit
      apoptosis in chondrocytes. The effect of LPA on the angiogenic capability of
      chondrocytes is not clear. This study aimed to investigate its effect on the
      angiogenic capability of human chondrocytes and the underlying mechanism of these
      effects. Human chondrocyte cell line, CHON-001, commercialized human chondrocytes
      (HC) derived from normal human articular cartilage, and human vascular
      endothelial cells (HUVECs) were used as cell models in this study. The angiogenic
      capability of chondrocytes was determined by capillary tube formation, monolayer
      permeability, cell migration, and cell proliferation. An angiogenesis protein
      array kit was used to evaluate the secretion of angiogenic factors in conditioned
      medium. Angiogenin, insulin-like growth factor-binding protein 1 (IGFBP-1),
      interleukin (IL)-8, monocyte chemoattractant protein-1 (MCP-1), matrix
      metalloproteinase (MMP)-9, and vascular endothelial growth factor (VEGF) mRNA and
      protein expressions were evaluated by Q-RT-PCR and EIA, respectively. LPA
      receptor (LPAR) expression was determined by RT-PCR. Signaling pathways were
      clarified using inhibitors, Western blot analysis, and reporter assays. The LPA
      treatment promoted the angiogenic capability of CHON-001 cells and HC, resulting
      in enhanced HUVEC capillary tube formation, monolayer permeability, migration,
      and cell growth. Angiogenin, IGFBP-1, IL-8, MCP-1, MMP-9, and VEGF mRNA and
      protein expressions were significantly enhanced in LPA-treated chondrocytes.
      LPA2, 3, 4 and 6 were expressed in CHON-001 and HC cells. Pretreatment with the
      Gi/o type G protein inhibitor, pertussis toxin (PTX), and the NF-kB inhibitor,
      PDTC, significantly inhibited LPA-induced angiogenin, IGFBP-1, IL-8, MCP-1, MMP
      9, and VEGF expressions in chondrocytes. The PTX pretreatment also inhibited LPA
      mediated NF-kB activation, suggesting the presence of active Gi/NF-kB signaling
      in CHON-001 and HC cells. The effect of LPA on the angiogenesis-inducing capacity
      of chondrocytes may be due to the increased angiogenesis factor expression via
      the Gi/NF-kB signaling pathway. 

PMID- 24879418
TI  - Anatomical response and infection of soybean during latent and pathogenic
      infection by type A and B of Phialophora gregata.
AB  - Growth and anatomical responses of plants during latent and pathogenic infection
      by fungal pathogens are not well understood. The interactions between soybean
      (Glycine max) and two types of the pathogen Phialophora gregata were investigated
      to determine how plants respond during latent and pathogenic infection. Stems of
      soybean cultivars with different or no genes for resistance to infection by P.
      gregata were inoculated with wildtype or GFP and RFP-labeled strains of types A
      or B of P. gregata. Plants were sectioned during latent and pathogenic infection,
      examined with transmitted light or fluorescent microscopy, and quantitative
      differences in vessels and qualitative differences in infection were assessed
      using captured images. During latent infection, the number of vessels was similar
      in resistant and susceptible plants infected with type A or B compared to the
      control, and fungal infection was rarely observed in vessels. During pathogenic
      infection, the resistant cultivars had 20 to 25% more vessels than the uninfected
      plants, and fungal hyphae were readily observed in the vessels. Furthermore,
      during the pathogenic phase in a resistant cultivar, P. gregata type A-GFP was
      limited to outside of the primary xylem, while P. gregata type B-RFP was observed
      in the primary xylem. The opposite occurred with the susceptible cultivar, where
      PgA-GFP was observed in the primary xylem and PgB-RFP was limited to the
      interfascicular region. In summary, soybean cultivars with resistance to BSR
      produced more vessels and can restrict or exclude P. gregata from the vascular
      system compared to susceptible cultivars. Structural resistance mechanisms
      potentially compensate for loss of vessel function and disrupted water movement.

PMID- 24879417
TI  - Pathogenic potential of Saccharomyces strains isolated from dietary supplements.
AB  - Saccharomyces cerevisiae plays a beneficial role in health because of its
      intrinsic nutritional value and bio-functional properties, which is why it is
      also used as a dietary supplement. However, the perception that S. cerevisiae is
      harmless has changed due to an increasing number of infections caused by this
      yeast. Given this scenario, we have tested whether viable strains contained in
      dietary supplements displayed virulence-associated phenotypic traits that could
      contribute to virulence in humans. We have also performed an in vivo study of the
      pathogenic potential of these strains using a murine model of systemic infection
      by intravenous inoculation. A total of 5 strains were isolated from 22 commercial
      products and tested. Results highlight one strain (D14) in terms of burden levels
      in brains and kidneys and ability to cause death, whereas the other two strains
      (D2 and D4) were considered of low virulence. Our results suggest a strong
      relationship between some of the virulence-associated phenotypic traits (ability
      to grow at 39 degrees C and pseudohyphal growth) and the in vivo virulence in a
      mouse model of intravenous inoculation for isolates under study. The isolate
      displaying greatest virulence (D14) was evaluated in an experimental murine model
      of gastrointestinal infection with immunosuppression and disruption of mucosal
      integrity, which are common risk factors for developing infection in humans, and
      results were compared with an avirulent strain (D23). We showed that D14 was able
      to spread to mesenteric nodes and distant organs under these conditions. Given
      the widespread consumption of dietary supplements, we recommend only safe strains
      be used. 

PMID- 24879420
TI  - Anomalous nanoinclusion effects of 2D MoS2 and WS2 nanosheets on the mechanical
      stiffness of polymer nanocomposites.
AB  - Polymer inorganic nanosheet composites hold great promise in enhancing their
      physical and mechanical properties by increasing the interfacial area. Herein, we
      demonstrate the nanoinclusion effects of two-dimensional (2D) molybdenum
      disulfide (MoS2) and tungsten disulfide (WS2) nanosheets on the mechanical
      properties of the poly(vinyl alcohol) (PVA) polymer. At very small amounts of
      nanosheets (0.9 wt% for MoS2 and 2.0 wt% for WS2), nanocomposite films exhibit up
      to 65% improved mechanical properties than the neat PVA film because of strong
      non-covalent polymer-filler interactions by means of large contact area induced
      by the 2D geometry of nanosheets. As demonstrated by the decrease in the
      crystallinity of PVA and the increase in the glass transition temperature, 2D
      MoS2 is a more attractive filler than 2D WS2 in terms of reinforcing mechanical
      properties of PVA. These findings fit well with a modified Halpin-Tsai (H-T)
      model including a nanoscale interfacial layer that can support the observed
      reinforcements with extremely small 2D filler loadings. This study highlights the
      strong interplay between the polymer and inorganic nanosheets which plays an
      important role in greatly improving the mechanical stability of nanocomposites. 

PMID- 24879416
TI  - Downregulation of rRNA transcription triggers cell differentiation.
AB  - Responding to various stimuli is indispensable for the maintenance of
      homeostasis. The downregulation of ribosomal RNA (rRNA) transcription is one of
      the mechanisms involved in the response to stimuli by various cellular processes,
      such as cell cycle arrest and apoptosis. Cell differentiation is caused by intra-
      and extracellular stimuli and is associated with the downregulation of rRNA
      transcription as well as reduced cell growth. The downregulation of rRNA
      transcription during differentiation is considered to contribute to reduced cell
      growth. However, the downregulation of rRNA transcription can induce various
      cellular processes; therefore, it may positively regulate cell differentiation.
      To test this possibility, we specifically downregulated rRNA transcription using
      actinomycin D or a siRNA for Pol I-specific transcription factor IA (TIF-IA) in
      HL-60 and THP-1 cells, both of which have differentiation potential. The
      inhibition of rRNA transcription induced cell differentiation in both cell lines,
      which was demonstrated by the expression of the common differentiation marker
      CD11b. Furthermore, TIF-IA knockdown in an ex vivo culture of mouse hematopoietic
      stem cells increased the percentage of myeloid cells and reduced the percentage
      of immature cells. We also evaluated whether differentiation was induced via the
      inhibition of cell cycle progression because rRNA transcription is tightly
      coupled to cell growth. We found that cell cycle arrest without affecting rRNA
      transcription did not induce differentiation. To the best of our knowledge, our
      results demonstrate the first time that the downregulation of rRNA levels could
      be a trigger for the induction of differentiation in mammalian cells.
      Furthermore, this phenomenon was not simply a reflection of cell cycle arrest.
      Our results provide a novel insight into the relationship between rRNA
      transcription and cell differentiation. 

PMID- 24879419
TI  - Hedgehog-PKA signaling and gnrh3 regulate the development of zebrafish gnrh3
      neurons.
AB  - GnRH neurons secrete GnRH that controls the development of the reproduction
      system. Despite many studies, the signals controlling the development of GnRH
      neurons from its progenitors have not been fully established. To understand the
      development of GnRH neurons, we examined the development of gnrh3-expressing
      cells using a transgenic zebrafish line that expresses green fluorescent protein
      (GFP) and LacZ driven by the gnrh3 promoter. GFP and LacZ expression
      recapitulated that of gnrh3 in the olfactory region, olfactory bulb and
      telencephalon. Depletion of gnrh3 by morpholinos led to a reduction of GFP- and
      gnrh3-expressing cells, while over-expression of gnrh3 mRNA increased the number
      of these cells. This result indicates a positive feed-forward regulation of gnrh3
      cells by gnrh3. The gnrh3 cells were absent in embryos that lack Hedgehog
      signaling, but their numbers were increased in embryos overexpressing shhb. We
      manipulated the amounts of kinase that antagonizes the Hedgehog signaling
      pathway, protein kinase A (PKA), by treating embryos with PKA activator forskolin
      or by injecting mRNAs encoding its constitutively active catalytic subunit (PKA*)
      and dominant negative regulatory subunit (PKI) into zebrafish embryos. PKA*
      misexpression or forskolin treatment decreased GFP cell numbers, while PKI
      misexpression led to ectopic production of GFP cells. Our data indicate that the
      Hedgehog-PKA pathway participates in the development of gnrh3-expressing neurons
      during embryogenesis. 

PMID- 24879421
TI  - Which Hodgkin's patients in the Unites States should be treated with BEACOPP?
AB  - The majority of patients with advanced Hodgkin lymphoma are cured with current
      standard therapy such as Adriamycin, bleomycin, vinblastine, and dacarbazine
      (ABVD). However, almost 20% of patients fail to achieve complete remission, and
      depending upon risk group, 20-30% experience relapse with prolonged follow-up.
      BEACOPP (bleomycin, etoposide, Adriamycin, cyclophosphamide, prednisone,
      procarbazine) was developed by the German Hodgkin Study Group (GHSG) to improve
      upon standard therapy by intensifying treatment and substituting etoposide and
      procarbazine for vinblastine and dacarbazine, respectively. In the HD9 trial,
      escalated BEACOPP was shown to be superior to COPP/ABVD with regard to time to
      treatment failure, but was associated with increased risk of secondary
      malignancies. Modifications of BEACOPP were developed to maintain efficacy while
      reducing the adverse effects. While several randomized trials have confirmed
      prolongation of progression-free survival with BEACOPP compared to ABVD, a
      survival advantage has been difficult to demonstrate. Given the comparable
      survival between BEACOPP and ABVD, as well as the greater toxicities of the
      former, including infertility, myelosuppression, and secondary malignancies, ABVD
      should remain the standard regimen for patients in the U.S. Newer regimens
      incorporating novel agents such as brentuximab vedotin may further improve the
      efficacy of current regimens.

PMID- 24879422
TI  - Astragaloside IV inhibits renal tubulointerstitial fibrosis by blocking TGF
      beta/Smad signaling pathway in vivo and in vitro.
AB  - Astragaloside IV (AS-IV) is a major active ingredient from Radix astragali, which
      has been considered as a renoprotective agent; however, its molecular mechanisms
      are unclear. Thus, we designed to investigate the renoprotective effects and
      mechanisms of AS-IV in rat model of renal fibrosis induced by unilateral ureteral
      obstruction (UUO) in vivo and TGF-beta1-stimulated rat renal fibroblasts (NRK
      49F) in vitro. Sprague-Dawley rats were randomly divided into six groups: sham
      operation, UUO, UUO/AS-IV (3.3, 10, 33 mg.kg(-1).d(-1)), and UUO/enalapril (4
      mg.kg(-1).d(-1)). Renal function, tubulointerstitial damage index score,
      extracellular matrix (ECM) deposition, and the expressions of TGF-beta1,
      connective tissue growth factor (CTGF), alpha-SMA, fibronectin, collagen I, III,
      Smad2/3, phosphorylated-Smad2/3, and Smad7 were measured. In addition, the
      expressions of CTGF, alpha-SMA, fibronectin, collagen I, III, Smad2/3,
      phosphorylated-Smad2/3, and Smad7 were measured in TGF-beta1-stiumlated NRK-49F
      cell line. AS-IV significantly decreased UUO-induced renal fibrosis and
      functional impairment, which are associated with inhibition of TGF-beta1, CTGF,
      alpha-SMA, and collagen matrix expression, and a decrease in serum creatinine and
      urea nitrogen. The renoprotective effects of AS-IV on fibrosis were associated
      with up-regulation of Smad7, thereby blocking up-regulations of TGF-beta1, CTGF,
      and alpha-SMA, and activation of phosphorylated-Smad2/3. These effects were
      further conformed in NRK-49F cell line stimulated by TGF-beta1. Moreover,
      knockdown of Smad7 gene in NRK-49F cells was able to prevent AS-IV-induced
      inhibition to Smad2/3 signaling activation, expression of CTGF, alpha-SMA, and
      ECM proteins in response to TGF-beta1. Renal tubulointerstitial fibrosis was
      attenuated by treatment with AS-IV, which was closely related to induction of
      Smad7, thereby inhibiting TGF-beta/Smad signaling.

PMID- 24879424
TI  - Ligand exchange on gold nanoparticles for drug delivery and enhanced therapeutic
      index evaluated in acute myeloid leukemia models.
AB  - Cancer chemotherapy is typically toxic. This problem could be addressed by using
      differences between cancer and normal cells for controlled delivery of drugs to
      cancer cells. One such difference is the ubiquitously elevated glutathione
      expression in cancer cells. We report a simple and versatile synthesis of water
      soluble gold nanoparticles passivated with amine-containing molecules, which
      allow for controlled drug release via ligand exchange with bio-available
      glutathione. Taking methotrexate-passivated gold nanoparticles (Au:MTX) as an
      example, drug delivery and controlled release via glutathione-mediated ligand
      exchange was evaluated. Furthermore, the possibility of using Au:MTX to improve
      therapeutic index in acute myeloid leukemia (AML) models was examined in vitro
      and in vivo. Au:MTX exhibited cancer selectivity in vitro. Au:MTX had an elevated
      potency toward an AML cell line THP-1 in a dosage range of 1-5 nM, and therefore
      an enhanced delivery of drug, whereas normal hematopoietic stem/progenitor cell
      (HSPC) growth was minimally affected by Au:MTX and MTX treatments within the same
      range of dosage. In vivo efficacy and safety of Au:MTX was evaluated in a murine
      xenotransplant model of primary human AML. Au:MTX treatment, compared to control
      groups including MTX-only and Au nanoparticle-only treatments, produced better
      leukemia suppression without added toxicity, indicating an enhanced therapeutic
      index.

PMID- 24879423
TI  - Defining the radiobiology of prostate cancer progression: An important question
      in translational prostate cancer research.
AB  - Prostate cancer is one of the most common malignancies affecting men worldwide.
      High mortality rates from advanced and metastatic prostate cancer in the United
      States are contrasted by a relatively indolent course in the majority of cases.
      This gives hope for finding methods that could direct personalized diagnostic,
      preventative, and treatment approaches to patients with prostate cancer. Recent
      advances in multiparametric magnetic resonance imaging (MP-MRI) offer a
      noninvasive diagnostic intervention which allows correlation of prostate tumor
      image characteristics with underlying biologic evidence of tumor progression. The
      power of MP-MRI includes examination of both local invasion and nodal disease and
      might overcome the challenges of analyzing the multifocal nature of prostate
      cancer. Future directions include a careful analysis of the genomic signature of
      individual prostatic lesions utilizing image-guided biopsies. This review
      examines the diagnostic potential of MRI in prostate cancer.

PMID- 24879425
TI  - Free-standing electrochemical electrode based on Ni(OH)2/3D graphene foam for
      nonenzymatic glucose detection.
AB  - Three-dimensional graphene foam (3DGF) is a superior sensing material because of
      its high conductivity, large specific surface area and wide electrochemical
      potential windows. In this work, hexagonal Ni(OH)2 nanosheets are deposited on
      the surface of chemical vapor deposition-grown 3DGF through a facial hydrothermal
      process without any auxiliary reagents. The morphology and structure of the
      composite are characterized by scanning electron microscopy (SEM), transmission
      electron microscope (TEM), Raman spectroscopy, and X-ray diffraction (XRD). Based
      on the Ni(OH)2/3DGF composite, a free-standing electrochemical electrode is
      fabricated. Being employed as a nonenzymatic glucose detection electrochemical
      electrode, it exhibits a high sensitivity (~2.65 mA mM(-1) cm(-2)), low detection
      limit (0.34 MUM) and excellent selectivity with a linear response from 1 MUM to
      1.17 mM. The excellent sensing properties of the Ni(OH)2/3DGF electrode may be
      attributed to the synergistic effect of the high electrocatalytic activity of
      Ni(OH)2 nanosheets and the high conductivity and large surface area of 3DGF. 

PMID- 24879426
TI  - The effects of triclosan on pluripotency factors and development of mouse
      embryonic stem cells and zebrafish.
AB  - Triclosan (TCS) poses potential risks to reproduction and development due to its
      endocrine-disrupting properties. However, the mechanism of TCS's effects on early
      embryonic development is little known. Embryonic stem cells (ESC) and zebrafish
      embryos provide valuable models for testing the toxic effects of environmental
      chemicals on early embryogenesis. In this study, mouse embryonic stem cells
      (mESC) were acutely exposed to TCS for 24 h, and general cytotoxicity and the
      effect of TCS on pluripotency were then evaluated. In addition, zebrafish embryos
      were exposed to TCS from 2- to 24-h post-fertilization (hpf), and their
      morphology was evaluated. In mESC, alkaline phosphatase staining was
      significantly decreased after treatment with the highest concentration of TCS (50
      MUM). Although the expression levels of Sox2 mRNA were not changed, the mRNA
      levels of Oct4 and Nanog in TCS-treated groups were significantly decreased
      compared to controls. In addition, the protein levels of Oct4, Sox2 and Nanog
      were significantly reduced in response to TCS treatment. MicroRNA (miR)-134, an
      expression inhibitor of pluripotency markers, was significantly increased in TCS
      treated mESC. In zebrafish experiments, after 24 hpf of treatment, the controls
      had developed to the late stage of somitogenesis, while embryos exposed to 300
      MUg/L of TCS were still at the early stage of somitogenesis, and three genes
      (Oct4, Sox2 and Nanog) were upregulated in treated groups when compared with the
      controls. The two models demonstrated that TCS may affect early embryonic
      development by disturbing the expression of the pluripotency markers (Oct4, Sox2
      and Nanog).

PMID- 24879427
TI  - In Planta Recognition of a Double-Stranded RNA Synthesis Protein Complex by a
      Potexviral RNA Silencing Suppressor.
AB  - RNA silencing plays an important antiviral role in plants and invertebrates. To
      counteract antiviral RNA silencing, most plant viruses have evolved viral
      suppressors of RNA silencing (VSRs). TRIPLE GENE BLOCK PROTEIN1 (TGBp1) of
      potexviruses is a well-characterized VSR, but the detailed mechanism by which it
      suppresses RNA silencing remains unclear. We demonstrate that transgenic
      expression of TGBp1 of plantago asiatica mosaic virus (PlAMV) induced
      developmental abnormalities in Arabidopsis thaliana similar to those observed in
      mutants of SUPPRESSOR OF GENE SILENCING3 (SGS3) and RNA-DEPENDENT RNA POLYMERASE6
      (RDR6) required for the trans-acting small interfering RNA synthesis pathway.
      PlAMV-TGBp1 inhibits SGS3/RDR6-dependent double-stranded RNA synthesis in the
      trans-acting small interfering RNA pathway. TGBp1 interacts with SGS3 and RDR6
      and coaggregates with SGS3/RDR6 bodies, which are normally dispersed in the
      cytoplasm. In addition, TGBp1 forms homooligomers, whose formation coincides with
      TGBp1 aggregation with SGS3/RDR6 bodies. These results reveal the detailed
      molecular function of TGBp1 as a VSR and shed new light on the SGS3/RDR6
      dependent double-stranded RNA synthesis pathway as another general target of
      VSRs.

PMID- 24879430
TI  - Stem cell treatment after cerebral ischemia regulates the gene expression of
      apoptotic molecules.
AB  - Evidence suggests that apoptosis contributes significantly to cell death after
      cerebral ischemia. Our recent studies that utilized human umbilical cord blood
      derived mesenchymal stem cells (hUCBSCs) demonstrated the potential of hUCBSCs to
      inhibit neuronal apoptosis in a rat model of CNS injury. Therefore, we
      hypothesize that intravenous administration of hUCBSCs after focal cerebral
      ischemia would reduce brain damage by inhibiting apoptosis and downregulating the
      upregulated apoptotic pathway molecules. Male Sprague-Dawley rats were obtained
      and randomly assigned to various groups. After the animals reached a desired
      weight, they were subjected to a 2 h middle cerebral artery occlusion (MCAO)
      procedure followed by 7 days of reperfusion. The hUCBSCs were obtained, cultured,
      and intravenously injected (0.25 * 10(6) cells or 1 * 10(6) cells) via the tail
      vein to separate groups of animals 24 h post-MCAO procedure. We performed various
      techniques including PCR microarray, hematoxylin and eosin, and TUNEL staining in
      addition to immunoblot and immunofluorescence analysis in order to investigate
      the effect of our treatment on regulation of apoptosis after focal cerebral
      ischemia. Most of the apoptotic pathway molecules which were upregulated after
      focal cerebral ischemia were downregulated after hUCBSCs treatment. Further, the
      staining techniques revealed a prominent reduction in brain damage and the extent
      of apoptosis at even the lowest dose of hUCBSCs tested in the present study. In
      conclusion, our treatment with hUCBSCs after cerebral ischemia in the rodent
      reduces brain damage by inhibiting apoptosis and downregulating the apoptotic
      pathway molecules. 

PMID- 24879428
TI  - Conditional Depletion of the Chlamydomonas Chloroplast ClpP Protease Activates
      Nuclear Genes Involved in Autophagy and Plastid Protein Quality Control.
AB  - Plastid protein homeostasis is critical during chloroplast biogenesis and
      responses to changes in environmental conditions. Proteases and molecular
      chaperones involved in plastid protein quality control are encoded by the nucleus
      except for the catalytic subunit of ClpP, an evolutionarily conserved serine
      protease. Unlike its Escherichia coli ortholog, this chloroplast protease is
      essential for cell viability. To study its function, we used a recently developed
      system of repressible chloroplast gene expression in the alga Chlamydomonas
      reinhardtii. Using this repressible system, we have shown that a selective
      gradual depletion of ClpP leads to alteration of chloroplast morphology, causes
      formation of vesicles, and induces extensive cytoplasmic vacuolization that is
      reminiscent of autophagy. Analysis of the transcriptome and proteome during ClpP
      depletion revealed a set of proteins that are more abundant at the protein level,
      but not at the RNA level. These proteins may comprise some of the ClpP
      substrates. Moreover, the specific increase in accumulation, both at the RNA and
      protein level, of small heat shock proteins, chaperones, proteases, and proteins
      involved in thylakoid maintenance upon perturbation of plastid protein
      homeostasis suggests the existence of a chloroplast-to-nucleus signaling pathway
      involved in organelle quality control. We suggest that this represents a
      chloroplast unfolded protein response that is conceptually similar to that
      observed in the endoplasmic reticulum and in mitochondria.

PMID- 24879431
TI  - A short-term effect of low-dose aspirin on major hemorrhagic risks in primary
      prevention: a case-crossover design.
AB  - BACKGROUND: Very few studies have examined the risk of short-term adverse
      hemorrhage of low-dose aspirin use in primary prevention. This case-crossover
      study examined the transient effect of low-dose aspirin use on major hemorrhagic
      risks. METHODS: A representative database of 1,000,000 patients randomly sampled
      from the Taiwan's National Health Insurance Research Database in 2000 was
      analyzed. The study cohort consisted of a total of 501,946 individuals, aged 30
      95 years old, at risk of a major bleeding event in 2000. A case-crossover study
      was used to retrieve data on 10,905 incident patients with major hemorrhagic
      complications (3,781 cerebral and 7,124 gastrointestinal) and prescribed low-dose
      aspirin (<=300 mg/day) from 2000-2008. A 56-day time window (~2 months) was used
      as the case period for which the odds ratio (OR) was estimated using the ratio of
      patients exposed during the 56-day case period only (1-56 days before the index
      date) compared to its corresponding 56-day control period only (57-112 days
      before the index date). RESULTS: Four hundred eighty-nine (4.5%) of the 10,905
      hemorrhagic patients had used low-dose aspirin during the 56-day case only
      period; 294 (2.7%) of the same patients had used low-dose aspirin during control
      only period. Low-dose aspirin use increase the risk of developing a major
      hemorrhage 1.33-fold (95% CI = 1.13-1.55, P<0.0001). Significance was found
      prominent in 4,453 non-hypertensive and non-diabetic subjects (Adjusted odds
      ratio = 1.88, 95% CI = 1.21-2.91). CONCLUSION: Transient low-dose aspirin use
      increases risk for major hemorrhagic events in Han Chinese.

PMID- 24879433
TI  - The Emerging Role of Reactive Oxygen Species Signaling during Lateral Root
      Development.
AB  - Overall root architecture is the combined result of primary and lateral root
      growth and is influenced by both intrinsic genetic programs and external signals.
      One of the main questions for root biologists is how plants control the number of
      lateral root primordia and their emergence through the main root. We recently
      identified S-phase kinase-associated protein2 (SKP2B) as a new early marker for
      lateral root development. Here, we took advantage of its specific expression
      pattern in Arabidopsis (Arabidopsis thaliana) in a cell-sorting and
      transcriptomic approach to generate a lateral root-specific cell sorting SKP2B
      data set that represents the endogenous genetic developmental program. We first
      validated this data set by showing that many of the identified genes have a
      function during root growth or lateral root development. Importantly, genes
      encoding peroxidases were highly represented in our data set. Thus, we next
      focused on this class of enzymes and showed, using genetic and chemical inhibitor
      studies, that peroxidase activity and reactive oxygen species signaling are
      specifically required during lateral root emergence but, intriguingly, not for
      primordium specification itself.

PMID- 24879432
TI  - Efficient purging of deleterious mutations in plants with haploid selfing.
AB  - In diploid organisms, selfing reduces the efficiency of selection in removing
      deleterious mutations from a population. This need not be the case for all
      organisms. Some plants, for example, undergo an extreme form of selfing known as
      intragametophytic selfing, which immediately exposes all recessive deleterious
      mutations in a parental genome to selective purging. Here, we ask how effectively
      deleterious mutations are removed from such plants. Specifically, we study the
      extent to which deleterious mutations accumulate in a predominantly selfing and a
      predominantly outcrossing pair of moss species, using genome-wide transcriptome
      data. We find that the selfing species purge significantly more nonsynonymous
      mutations, as well as a greater proportion of radical amino acid changes which
      alter physicochemical properties of amino acids. Moreover, their purging of
      deleterious mutation is especially strong in conserved regions of protein-coding
      genes. Our observations show that selfing need not impede but can even accelerate
      the removal of deleterious mutations, and do so on a genome-wide scale. 

PMID- 24879434
TI  - Tree species traits but not diversity mitigate stem breakage in a subtropical
      forest following a rare and extreme ice storm.
AB  - Future climates are likely to include extreme events, which in turn have great
      impacts on ecological systems. In this study, we investigated possible effects
      that could mitigate stem breakage caused by a rare and extreme ice storm in a
      Chinese subtropical forest across a gradient of forest diversity. We used
      Bayesian modeling to correct stem breakage for tree size and variance components
      analysis to quantify the influence of taxon, leaf and wood functional traits, and
      stand level properties on the probability of stem breakage. We show that the
      taxon explained four times more variance in individual stem breakage than did
      stand level properties; trees with higher specific leaf area (SLA) were less
      susceptible to breakage. However, a large part of the variation at the taxon
      scale remained unexplained, implying that unmeasured or undefined traits could be
      used to predict damage caused by ice storms. When aggregated at the plot level,
      functional diversity and wood density increased after the ice storm. We suggest
      that for the adaption of forest management to climate change, much can still be
      learned from looking at functional traits at the taxon level. 

PMID- 24879437
TI  - Improving electroencephalographic source localization of epileptogenic zones with
      time-frequency analysis.
AB  - The combination of recently developed methods for electroencephalographic (EEG)
      space-time-frequency analysis can provide noninvasive functional neuroimages
      necessary for obtaining an accurate localization of the epileptogenic zone. The
      aim of this study was to determine if time-frequency (TF) analysis, followed by
      EEG source localization, would improve the detection and identification of
      epileptogenic and related activity. Seventeen patients with refractory frontal
      lobe epilepsy (FLE) were studied using video EEG recording. TF analysis
      identified the first epileptogenic EEG changes. Using the Bayesian model
      averaging (BMA) approach, we compared brain electromagnetic tomographic (BET)
      images, constructed from the TF domain, with BET images constructed from the time
      domain only. We determined if the localization identified by BET images was
      concordant with the localization from medical history and video EEG recording. TF
      analysis provided a clear display of subtle EEG features, including EEG
      lateralization, and more concordant and delimited epileptogenic zones, compared
      with time-domain source analysis. In conclusion, EEG TF analysis improves source
      localization. After a thorough validation, this methodology could become a useful
      noninvasive tool for localizing the epileptogenic zone in clinical practice. 

PMID- 24879438
TI  - Circulating Tumor Cells: What Is in It for the Patient? A Vision towards the
      Future.
AB  - Knowledge on cellular signal transduction pathways as drivers of cancer growth
      and metastasis has fuelled development of "targeted therapy" which "targets"
      aberrant oncogenic signal transduction pathways. These drugs require nearly
      invariably companion diagnostic tests to identify the tumor-driving pathway and
      the cause of the abnormal pathway activity in a tumor sample, both for therapy
      response prediction as well as for monitoring of therapy response and emerging
      secondary drug resistance. Obtaining sufficient tumor material for this analysis
      in the metastatic setting is a challenge, and circulating tumor cells (CTCs) may
      provide an attractive alternative to biopsy on the premise that they can be
      captured from blood and the companion diagnostic test results are correctly
      interpreted. We discuss novel companion diagnostic directions, including the
      challenges, to identify the tumor driving pathway in CTCs, which in combination
      with a digital pathology platform and algorithms to quantitatively interpret
      complex CTC diagnostic results may enable optimized therapy response prediction
      and monitoring. In contrast to CTC-based companion diagnostics, CTC enumeration
      is envisioned to be largely replaced by cell free tumor DNA measurements in blood
      for therapy response and recurrence monitoring. The recent emergence of novel in
      vitro human model systems in the form of cancer-on-a-chip may enable elucidation
      of some of the so far elusive characteristics of CTCs, and is expected to
      contribute to more efficient CTC capture and CTC-based diagnostics. 

PMID- 24879436
TI  - Replication of 6 obesity genes in a meta-analysis of genome-wide association
      studies from diverse ancestries.
AB  - Obesity is a major public health problem with a significant genetic component.
      Multiple DNA polymorphisms/genes have been shown to be strongly associated with
      obesity, typically in populations of European descent. The aim of this study was
      to verify the extent to which 6 confirmed obesity genes (FTO, CTNNBL1, ADRB2,
      LEPR, PPARG and UCP2 genes) could be replicated in 8 different samples (n =
      11,161) and to explore whether the same genes contribute to obesity
      susceptibility in populations of different ancestries (five Caucasian, one
      Chinese, one African-American and one Hispanic population). GWAS-based data sets
      with 1000 G imputed variants were tested for association with obesity phenotypes
      individually in each population, and subsequently combined in a meta-analysis.
      Multiple variants at the FTO locus showed significant associations with BMI, fat
      mass (FM) and percentage of body fat (PBF) in meta-analysis. The strongest
      association was detected at rs7185735 (P-value = 1.01*10(-7) for BMI, 1.80*10(-6)
      for FM, and 5.29*10(-4) for PBF). Variants at the CTNNBL1, LEPR and PPARG loci
      demonstrated nominal association with obesity phenotypes (meta-analysis P-values
      ranging from 1.15*10(-3) to 4.94*10(-2)). There was no evidence of association
      with variants at ADRB2 and UCP2 genes. When stratified by sex and ethnicity, FTO
      variants showed sex-specific and ethnic-specific effects on obesity traits. Thus,
      it is likely that FTO has an important role in the sex- and ethnic-specific risk
      of obesity. Our data confirmed the role of FTO, CTNNBL1, LEPR and PPARG in
      obesity predisposition. These findings enhanced our knowledge of genetic
      associations between these genes and obesity-related phenotypes, and provided
      further justification for pursuing functional studies of these genes in the
      pathophysiology of obesity. Sex and ethnic differences in genetic susceptibility
      across populations of diverse ancestries may contribute to a more targeted
      prevention and customized treatment of obesity.

PMID- 24879439
TI  - Recombinant TLR5 agonist CBLB502 promotes NK cell-mediated anti-CMV immunity in
      mice.
AB  - Prior work using allogeneic bone marrow transplantation (allo-BMT) models showed
      that peritransplant administration of flagellin, a toll-like receptor 5 (TLR5)
      agonist protected murine allo-BMT recipients from CMV infection while limiting
      graft-vs-host disease (GvHD). However, the mechanism by which flagellin-TLR5
      interaction promotes anti-CMV immunity was not defined. Here, we investigated the
      anti-CMV immunity of NK cells in C57BL/6 (B6) mice treated with a highly purified
      cGMP grade recombinant flagellin variant CBLB502 (rflagellin) followed by murine
      CMV (mCMV) infection. A single dose of rflagellin administered to mice between 48
      to 72 hours prior to MCMV infection resulted in optimal protection from mCMV
      lethality. Anti-mCMV immunity in rflagellin-treated mice correlated with a
      significantly reduced liver viral load and increased numbers of Ly49H+ and Ly49D+
      activated cytotoxic NK cells. Additionally, the increased anti-mCMV immunity of
      NK cells was directly correlated with increased numbers of IFN-gamma, granzyme B-
      and CD107a producing NK cells following mCMV infection. rFlagellin-induced anti
      mCMV immunity was TLR5-dependent as rflagellin-treated TLR5 KO mice had ~10-fold
      increased liver viral load compared with rflagellin-treated WT B6 mice. However,
      the increased anti-mCMV immunity of NK cells in rflagellin-treated mice is
      regulated indirectly as mouse NK cells do not express TLR5. Collectively, these
      data suggest that rflagellin treatment indirectly leads to activation of NK
      cells, which may be an important adjunct benefit of administering rflagellin in
      allo-BMT recipients. 

PMID- 24879440
TI  - Skp1-Cullin-F-box (SCF)-type ubiquitin ligase FBXW7 negatively regulates
      spermatogonial stem cell self-renewal.
AB  - Spermatogonial stem cells (SSCs) undergo self-renewal divisions to support
      spermatogenesis throughout life. Although several positive regulators of SSC self
      renewal have been discovered, little is known about the negative regulators.
      Here, we report that F-box and WD-40 domain protein 7 (FBXW7), a component of the
      Skp1-Cullin-F-box-type ubiquitin ligase, is a negative regulator of SSC self
      renewal. FBXW7 is expressed in undifferentiated spermatogonia in a cell cycle
      dependent manner. Although peptidyl-prolyl cis/trans isomerase NIMA-interacting 1
      (PIN1), essential for spermatogenesis, is thought to destroy FBXW7, Pin1
      depletion decreased FBXW7 expression. Spermatogonial transplantation showed that
      Fbxw7 overexpression compromised SSC activity whereas Fbxw7 deficiency enhanced
      SSC colonization and caused accumulation of undifferentiated spermatogonia,
      suggesting that the level of FBXW7 is critical for self-renewal and
      differentiation. Screening of putative FBXW7 targets revealed that Fbxw7
      deficiency up-regulated myelocytomatosis oncogene (MYC) and cyclin E1 (CCNE1).
      Although depletion of Myc/Mycn or Ccne1/Ccne2 compromised SSC activity,
      overexpression of Myc, but not Ccne1, increased colonization of SSCs. These
      results suggest that FBXW7 regulates SSC self-renewal in a negative manner by
      degradation of MYC. 

PMID- 24879441
TI  - Methylated glycans as conserved targets of animal and fungal innate defense.
AB  - Effector proteins of innate immune systems recognize specific non-self epitopes.
      Tectonins are a family of beta-propeller lectins conserved from bacteria to
      mammals that have been shown to bind bacterial lipopolysaccharide (LPS). We
      present experimental evidence that two Tectonins of fungal and animal origin have
      a specificity for O-methylated glycans. We show that Tectonin 2 of the mushroom
      Laccaria bicolor (Lb-Tec2) agglutinates Gram-negative bacteria and exerts
      toxicity toward the model nematode Caenorhabditis elegans, suggesting a role in
      fungal defense against bacteria and nematodes. Biochemical and genetic analysis
      of these interactions revealed that both bacterial agglutination and
      nematotoxicity of Lb-Tec2 depend on the recognition of methylated glycans, namely
      O-methylated mannose and fucose residues, as part of bacterial LPS and nematode
      cell-surface glycans. In addition, a C. elegans gene, termed samt-1, coding for a
      candidate membrane transport protein for the presumptive donor substrate of
      glycan methylation, S-adenosyl-methionine, from the cytoplasm to the Golgi was
      identified. Intriguingly, limulus lectin L6, a structurally related antibacterial
      protein of the Japanese horseshoe crab Tachypleus tridentatus, showed properties
      identical to the mushroom lectin. These results suggest that O-methylated glycans
      constitute a conserved target of the fungal and animal innate immune system. The
      broad phylogenetic distribution of O-methylated glycans increases the spectrum of
      potential antagonists recognized by Tectonins, rendering this conserved protein
      family a universal defense armor. 

PMID- 24879442
TI  - The GTPase-activating protein GIT2 protects against colitis by negatively
      regulating Toll-like receptor signaling.
AB  - G protein-coupled receptor kinase-interactor 2 (GIT2) regulates thymocyte
      positive selection, neutrophil-direction sensing, and cell motility during immune
      responses by regulating the activity of the small GTPases ADP ribosylation
      factors (Arfs) and Ras-related C3 botulinum toxin substrate 1 (Rac1). Here, we
      show that Git2-deficient mice were more susceptible to dextran sodium sulfate
      (DSS)-induced colitis, Escherichia coli, or endotoxin-shock challenge, and a
      dramatic increase in proinflammatory cytokines was observed in Git2 knockout mice
      and macrophages. GIT2 is a previously unidentified negative regulator of Toll
      like receptor (TLR)-induced NF-kappaB signaling. The ubiquitination of TNF
      receptor associated factor 6 (TRAF6) is critical for the activation of NF-kappaB.
      GIT2 terminates TLR-induced NF-kappaB and MAPK signaling by recruiting the
      deubiquitinating enzyme Cylindromatosis to inhibit the ubiquitination of TRAF6.
      Finally, we show that the susceptibility of Git2-deficient mice to DSS-induced
      colitis depends on TLR signaling. Thus, we show that GIT2 is an essential
      terminator of TLR signaling and that loss of GIT2 leads to uncontrolled
      inflammation and severe organ damage. 

PMID- 24879445
TI  - Moving from idea to action: promoting physical activity by empowering
      adolescents.
AB  - BACKGROUND: Physical activity provides fundamental health benefits for children
      and youth. The aim of the study was to explore the possibility of conducting an
      empowerment-inspired intervention and examine the impact of the intervention in
      promoting moderate and vigorous physical activity (MVPA) among adolescents.
      METHOD: A nonrandomized trial with a concurrent control group was carried out.
      Physical activity data were collected before and after the intervention with
      daily questions by short message service. Self-efficacy, social support, and
      attitude were also measured before and after the intervention since they were
      possible mediators. RESULTS: The intervention was created by the students, the
      researchers, and the teachers using an empowerment-based approach. Students in
      the intervention group (n = 21) increased their MVPA on average by 4.9 (SD =
      28.9) minutes per day, and students in the control group (n = 25) reduced their
      MVPA on average by 25.4 (SD = 23.0) minutes per day (p = .000). CONCLUSIONS: The
      intervention might have contributed to a promotion of physical activity among
      students in the intervention group. The most valuable contribution this study
      provides is the knowledge that it is possible to develop and conduct an
      empowerment-inspired intervention to promote adolescent physical activity.

PMID- 24879443
TI  - Expression of epidermal fatty acid binding protein (E-FABP) in septoclasts in the
      growth plate cartilage of mice.
AB  - n-3 Polyunsaturated fatty acids play a role in regulating the growth of the long
      bones. Fatty acid-binding proteins (FABPs) bind and transport hydrophobic long
      chain fatty acids intracellularly, and epidermal-type FABP (E-FABP) has an
      affinity for n-3 fatty acids. This study aimed to clarify the localization of E
      FABP in the growth plate of the mouse tibia. At the chondro-osseous junction
      (COJ) of the growth plate, E-FABP-immunoreactivity was exclusively localized in
      mononuclear, spindle-shaped cells with several long processes. These E-FABP
      immunoreactive cells were identified as being septoclasts, i.e., cells that
      resorb uncalcified transverse septa. The processes of these immunoreactive
      septoclasts terminated between the longitudinal and transverse septa. E-FABP
      immunoreactivity was found in the entire cytoplasm and on the mitochondrial outer
      membrane. In ontogeny, immunoreactive septoclasts were observed immediately after
      emergence of the primary ossifying center and were distributed not only at the
      COJ but also in the metaphysis near the COJ. The number of septoclasts increased
      at the postnatal age of 1 week (P1w)-P2w, and thereafter gradually decreased; and
      the cells became concentrated at the COJ after P3w-P4w. The immunoreactivity for
      peroxisome proliferator-activated receptor (PPAR)beta/delta was detected in these
      E-FABP-immunoreactive septoclasts. The present results suggest that fatty acids,
      preferably n-3 ones, are intracellularly transported by E-FABP to various
      targets, including mitochondria and nucleus, in which PPARbeta/delta may play
      functional roles in the transcriptional regulation of genes involved in the
      endochondral ossification.

PMID- 24879447
TI  - Trauma Surgery-Controversies and Shifting Management Paradigms.

PMID- 24879448
TI  - Kuopio Treatment Strategy after Deep Sternal Wound Infection.
AB  - The authors and the Editor wish to inform readers of the introduction to the
      following article L T BERG AND P JAAKKOLA: 'Kuopio Treatment Strategy after Deep
      Sternal Wound Infection' SCANDINAVIAN JOURNAL OF SURGERY MARCH 2013 1021 3-8,
      DOI101177/145749691310200102 : that it contains material used without attribution
      from ALEXANDER ANDERSEN JUHL, VIBEKE KOUDAHL AND TINE ENGBERG DAMSGAARD 'DEEP
      STERNAL WOUND INFECTION AFTER OPEN HEART SURGERY - RECONSTRUCTIVE OPTIONS'
      SCANDINAVIAN CARDIOVASCULAR JOURNAL OCT 2012, VOL 46, NO 5 254-261 DOI
      103109/140174312012674549: The authors wish to apologise to Alexander Andersen
      Juhl, Vibeke Koudahl and Tine Engberg Damsgaard, and to Scandinavian
      Cardiovascular Journal and readers.

PMID- 24879444
TI  - Identifying the science and technology dimensions of emerging public policy
      issues through horizon scanning.
AB  - Public policy requires public support, which in turn implies a need to enable the
      public not just to understand policy but also to be engaged in its development.
      Where complex science and technology issues are involved in policy making, this
      takes time, so it is important to identify emerging issues of this type and
      prepare engagement plans. In our horizon scanning exercise, we used a modified
      Delphi technique. A wide group of people with interests in the science and policy
      interface (drawn from policy makers, policy adviser, practitioners, the private
      sector and academics) elicited a long list of emergent policy issues in which
      science and technology would feature strongly and which would also necessitate
      public engagement as policies are developed. This was then refined to a short
      list of top priorities for policy makers. Thirty issues were identified within
      broad areas of business and technology; energy and environment; government,
      politics and education; health, healthcare, population and aging; information,
      communication, infrastructure and transport; and public safety and national
      security.

PMID- 24879446
TI  - African American community leaders' policy recommendations for reducing racial
      disparities in HIV infection, treatment, and care: results from a community-based
      participatory research project in Philadelphia, Pennsylvania.
AB  - African Americans account for 45% of new HIV infections in the United States.
      Little empirical research investigates African American community leaders'
      normative recommendations for addressing these disparities. Philadelphia's HIV
      infection rate is 5 times the national average, nearly 70% of new infections are
      among African Americans, and 2% of African Americans in Philadelphia are living
      with HIV/AIDS. Using a community-based participatory research approach, we
      convened focus groups among 52 African American community leaders from diverse
      backgrounds to solicit normative recommendations for reducing Philadelphia's
      racial disparities in HIV infection. Leaders recommended that (a) Philadelphia's
      city government should raise awareness about HIV/AIDS with media campaigns
      featuring local leaders, (b) local HIV-prevention interventions should address
      social and structural factors influencing HIV risks rather than focus exclusively
      on mode of HIV transmission, (c) resources should be distributed to the most
      heavily affected neighborhoods of Philadelphia, and (d) faith institutions should
      play a critical role in HIV testing, treatment, and prevention efforts. We
      developed a policy memo highlighting these normative recommendations for how to
      enhance local HIV prevention policy. This policy memo led to Philadelphia City
      Council hearings about HIV/AIDS in October 2010 and subsequently informed local
      HIV/AIDS prevention policy and development of local HIV prevention interventions.
      This community-based participatory research case study offers important lessons
      for effectively engaging community leaders in research to promote HIV/AIDS policy
      change. 

PMID- 24879449
TI  - Arrhythmic syncope in neurogenic orthostatic hypotension: two case reports.
AB  - Patients with autonomic failure experience orthostatic hypotension (OH) often
      leading to syncope. Arrhythmias may cause severe syncope, characterized by an
      increased risk of mortality. We report two cases of patients with primary
      autonomic neuropathy suffering from both severe OH and arrhythmic syncope. 

PMID- 24879450
TI  - Filamentous pathogen effector functions: of pathogens, hosts and microbiomes.
AB  - Microorganisms play essential roles in almost every environment on earth. For
      instance, microbes decompose organic material, or establish symbiotic
      relationships that range from pathogenic to mutualistic. Symbiotic relationships
      have been particularly well studied for microbial plant pathogens and have
      emphasized the role of effectors; secreted molecules that support host
      colonization. Most effectors characterized thus far play roles in deregulation of
      host immunity. Arguably, however, pathogens not only deal with immune responses
      during host colonization, but also encounter other microbes including
      competitors, (myco)parasites and even potential co-operators. Thus, part of the
      effector catalog may target microbiome co-inhabitants rather than host
      physiology. 

PMID- 24879451
TI  - Synthesis of free-standing, curved Si nanowires through mechanical failure of a
      catalyst during metal assisted chemical etching.
AB  - The fabrication of orderly arrays of free-standing, curved Si nanowires over
      large areas (1 cm * 1 cm) was demonstrated by means of interference lithography
      and intentional mechanical failure of a perforated Au catalyst during metal
      assisted chemical etching. Photoresist microgrooves were deposited on the
      perforated Au film to cause uneven etching which resulted in the build-up of
      bending stresses in the Au film to the point of catastrophic failure. By
      considering the initial positions of the holes in the perforated Au film relative
      to the photoresist constraints, the precise location of the fracture can be
      predicted using simple beam mechanics. Therefore, the type of curved nanowires
      obtained can be designed with a high degree of reliability and control. Four
      distinct types of nanowire arrangements were demonstrated for this study. 

PMID- 24879452
TI  - Asystole following regadenoson infusion in stable outpatients.
AB  - Regadenoson is a selective A2A receptor agonist approved for use as a
      pharmacologic stress agent for myocardial perfusion imaging after several
      multicenter trials demonstrated its equivalence in diagnostic accuracy for the
      detection of coronary artery disease and a decreased incidence of serious side
      effects as compared to adenosine. Recently, the FDA released a safety
      announcement advising of the rare but serious risk of heart attack and death
      associated with regadenoson and adenosine in cardiac stress testing, particularly
      in patients with unstable angina or cardiovascular instability. We report two
      cases of asystole with hemodynamic collapse in stable outpatients soon after
      receiving a standard regadenoson injection. The prevalence of potentially life
      threatening bradycardia, including asystole, associated with the use of
      regadenoson may be greater than previously expected. These cases highlight the
      need for cardiac stress labs to anticipate the potential for serious side effects
      with all patients during the administration of coronary vasodilators.

PMID- 24879453
TI  - Quantitative interpretation of FDG PET/CT with myocardial perfusion imaging
      increases diagnostic information in the evaluation of cardiac sarcoidosis.
AB  - BACKGROUND: FDG PET/CT with myocardial perfusion imaging is a useful method for
      evaluating cardiac sarcoidosis (CS), but interpretation is not standardized. We
      developed a method for quantification of cardiac FDG PET/CT and evaluated its
      relationship to conventional interpretation, perfusion defects, clinical events,
      and immunosuppressive treatment. METHODS AND RESULTS: FDG PET/CT with MPI studies
      performed for CS (n = 38) were retrospectively compared to negative control
      studies acquired for oncologic indications (n = 10). Quantitative measures of FDG
      volume-intensity (Cardiac Metabolic Activity, CMA) was performed using
      standardized uptake values (SUVs). CMA (477.7 +/- 909 vs 0.55 +/- 2.1 vs 0.3 +/-
      0.3 g glucose, P = .02) was significantly greater in visually FDG-positive
      studies compared to visually negative and oncologic negative studies. Among
      patients with CS, CMA was greater in studies with an EF < 50% (760.3 +/- 1,148 vs
      87.4 +/- 161 g glucose, P = .03) and preceding an adverse clinical event (1,095
      +/- 1,253 vs 73 +/- 144 g glucose, P = .006). CMA was the only independent
      predictor of events by multivariate analysis. In patients with repeat
      examinations (n = 7), CMA decreased with prednisone treatment in 5 of 6 patients.
      CONCLUSIONS: Quantification of FDG uptake in CS correlates with lower EFs,
      clinical events, and immunosuppression treatment.

PMID- 24879454
TI  - Changing histopathological diagnostics by genome-based tumor classification.
AB  - Traditionally, tumors are classified by histopathological criteria, i.e., based
      on their specific morphological appearances. Consequently, current therapeutic
      decisions in oncology are strongly influenced by histology rather than underlying
      molecular or genomic aberrations. The increase of information on molecular
      changes however, enabled by the Human Genome Project and the International Cancer
      Genome Consortium as well as the manifold advances in molecular biology and high
      throughput sequencing techniques, inaugurated the integration of genomic
      information into disease classification. Furthermore, in some cases it became
      evident that former classifications needed major revision and adaption. Such
      adaptations are often required by understanding the pathogenesis of a disease
      from a specific molecular alteration, using this molecular driver for targeted
      and highly effective therapies. Altogether, reclassifications should lead to
      higher information content of the underlying diagnoses, reflecting their
      molecular pathogenesis and resulting in optimized and individual therapeutic
      decisions. The objective of this article is to summarize some particularly
      important examples of genome-based classification approaches and associated
      therapeutic concepts. In addition to reviewing disease specific markers, we focus
      on potentially therapeutic or predictive markers and the relevance of molecular
      diagnostics in disease monitoring. 

PMID- 24879456
TI  - False-negative diffusion-weighted imaging in acute stroke and its frequency in
      anterior and posterior circulation ischemia.
AB  - OBJECTIVE: We aimed to investigate the location and size of ischemic stroke
      lesions that were frequently overlooked by diffusion-weighted imaging (DWI).
      MATERIALS AND METHODS: We retrospectively reviewed the medical records of 162
      patients who had symptoms suggesting ischemic stroke. National Institutes of
      Health Stroke Scale and Modified Rankin Scale scores, lesion size, magnetic
      resonance imaging (MRI) findings, delay between onset of symptoms and initial MRI
      (MRI latency), and vascular distribution of the stroke lesions were analyzed in
      patients with false-negative DWI findings. RESULTS: Of the 116 patients with a
      final diagnosis of acute ischemic stroke, 11 patients (9.48%) had false-negative
      DWI findings in the initial period. The mean (SD) MRI latency was 4.3 (1.2)
      hours. There was no statistically significant difference in point of lesion size,
      the National Institutes of Health Stroke Scale, and the Modified Rankin Scales
      scores. CONCLUSIONS: False-negative DWI findings in acute stroke can be observed
      both in association with the posterior circulation/small lesions and the anterior
      circulation/large lesions.

PMID- 24879455
TI  - GWAS to Sequencing: Divergence in Study Design and Analysis.
AB  - The success of genome-wide association studies (GWAS) in uncovering genetic risk
      factors for complex traits has generated great promise for the complete data
      generated by sequencing. The bumpy transition from GWAS to whole-exome or whole
      genome association studies (WGAS) based on sequencing investigations has
      highlighted important differences in analysis and interpretation. We show how the
      loss in power due to the allele frequency spectrum targeted by sequencing is
      difficult to compensate for with realistic effect sizes and point to study
      designs that may help. We discuss several issues in interpreting the results,
      including a special case of the winner's curse. Extrapolation and prediction
      using rare SNPs is complex, because of the selective ascertainment of SNPs in
      case-control studies and the low amount of information at each SNP, and naive
      procedures are biased under the alternative. We also discuss the challenges in
      tuning gene-based tests and accounting for multiple testing when genes have very
      different sets of SNPs. The examples we emphasize in this paper highlight the
      difficult road we must travel for a two-letter switch. 

PMID- 24879457
TI  - Neuroradiological features of papillary glioneuronal tumor: a study of 8 cases.
AB  - OBJECTIVE: The purpose of this study was to characterize the magnetic resonance
      imaging (MRI), and computed tomographic (CT) findings in a series of 8 patients
      with papillary glioneuronal tumor (PGNT). METHODS: The routine MRI (n = 8), DWI
      (n = 7), and CT (n = 4) of 8 PGNTs verified by pathologic examination were
      reviewed. The location, internal architecture, calcification, attenuation value
      on CT; and signal features and degree of enhancement of the lesions on MRI were
      evaluated. RESULTS: Papillary glioneuronal tumor showed relatively characteristic
      imaging features as well-demarcated masses with cystic degeneration,
      calcification, and inhomogeneous enhancement. Six of the 8 cases were located in
      the periventricular area. The solid part of the lesion was isointense (n = 5/8)
      or hypointense (n = 3/8) to gray matter on T1-weighted imaging. Diffusion
      weighted imaging presented heterogeneous hypointensity and isointensity (n = 4/7)
      or homogeneous hypointensity (n = 3/7) in the solid part of the lesion.
      CONCLUSIONS: The location adjacent to lateral ventricle, isointensity on T1
      weighted imaging, and low signal on DWI may be of some specificity to PGNT.

PMID- 24879458
TI  - Epicardial fat and coronary artery calcification in patients on long-term
      hemodialysis.
AB  - INTRODUCTION: Recent studies have shown a significant correlation between
      increased epicardial fat volume (EFV) and mortality, coronary artery disease
      events, and measures of coronary atherosclerotic burden, for example, coronary
      calcium. Patients with chronic kidney disease on hemodialysis have an increased
      prevalence of coronary atherosclerosis and coronary calcium. The mechanisms
      underlying both may differ from patients with normal kidney function. Only
      limited data are available on the relationship between epicardial fat and
      coronary calcium in these patients. METHODS: Ninety-three consecutive patients
      (62 men and 31 women; mean age, 55 +/- 11 years) with chronic kidney failure on
      regular hemodialysis underwent computed tomography for coronary calcium scoring
      as well as assessment of cardiovascular risk factors. Calcium scoring was
      performed using a low-dose, prospectively ECG-triggered high pitch spiral
      acquisition protocol (dual-source computed tomography, 280-millisecond (ms)
      rotation, 2 * 128 * 0.6-mm collimation, 120-kV tube voltage, 80-mA.s tube
      current). Cross-sectional images were reconstructed with 3.0-mm thickness, 1.5-mm
      increment, and a medium sharp reconstruction kernel (B35f). Agatston score and
      EVF were analyzed in a semiautomatic fashion using dedicated software. RESULTS:
      The mean duration of dialysis was 5.7 years. Of all patients, 93% had arterial
      hypertension, 66% had hyperlipidemia, 30% were diabetic, and 49.5% were current
      or prior smokers. The mean body mass index (BMI) was 27 +/- 4 kg/m. The mean EFV
      was 162 +/- 80 mL, and the mean coronary artery calcification (CAC) was 765 +/-
      1391 Agatston units (AU). In univariable and multivariable analysis, EFV was
      significantly correlated to BMI (P < 0.05) and age (P = 0.021), but not to CAC (P
      = 0.106). In subanalysis for values binned by median, we also found a significant
      correlation between EFV (binned) and smoking (P = 0.49) as well as a significant
      correlation between EFV (binned) and CAC for 46 patients younger than 55 years
      (median age). CONCLUSION: The epicardial fat volume in patients with chronic
      kidney disease and on hemodialysis is significantly correlated to BMI, age, and
      smoking but, with the exception of younger patients, not to the coronary calcium
      score. Our data suggest that in this special patient cohort, other mechanisms
      might influence the genesis of coronary calcification.

PMID- 24879459
TI  - Differences in dynamic susceptibility contrast MR perfusion maps generated by
      different methods implemented in commercial software.
AB  - PURPOSE: There are several potential sources of difference that can influence the
      reproducibility of magnetic resonance (MR) perfusion values. We aimed to
      investigate the reproducibility and variability of dynamic susceptibility
      contrast (DSC) MR imaging (MRI) parameters obtained from identical source data by
      using 2 commercially available software applications with different
      postprocessing algorithms. METHODS AND MATERIALS: We retrospectively evaluated
      DSC-MRI data sets of 24 consecutive patients with glioblastoma multiforme.
      Perfusion data were postprocessed with 2 commercial software packages, NordicICE
      (NordicNeuroLab, Bergen, Norway) and GE Brainstat (GE Healthcare, Milwaukee,
      Wis), each of which offers the possibility of different algorithms. We focused
      the comparison on their main analysis issues, that is, the gamma-variate fitting
      function (GVF) and the arterial input function (AIF). Two regions of interest
      were placed on maps of perfusion parameters (cerebral blood volume [CBV],
      cerebral blood flow [CBF], mean transit time [MTT]): one around tumor hot spot
      and one in the contralateral normal brain. A one-way repeated-measures analysis
      of variance was conducted to determine whether there was a significant difference
      in the calculated MTT, CBV, and CBF values. RESULTS: As regards NordicICE
      software application, the use of AIF is significant (P = 0.048) but not the use
      of GVF (P = 0.803) for CBV values. Additionally, in GE, the calculation method
      discloses a statistical effect on data. Comparing similar GE-NordicICE
      algorithms, both method (P = 0.005) and software (P < 0.0001) have a statistical
      effect in the difference. Leakage-corrected and uncorrected normalized CBV (nCBV)
      values are statistically equal. No statistical differences have been found in
      nMTT values when directly calculated. Values of nCBF are affected by the use of
      GVF. CONCLUSION: The use of a different software application determines different
      results, even if the algorithms seem to be the same. The introduction of AIF in
      the data postprocessing determines a higher estimates variability that can make
      interhospital and intrahospital examinations not completely comparable. A simpler
      approach based on raw curve analysis produces more stable results.

PMID- 24879460
TI  - A versatile system for USER cloning-based assembly of expression vectors for
      mammalian cell engineering.
AB  - A new versatile mammalian vector system for protein production, cell biology
      analyses, and cell factory engineering was developed. The vector system applies
      the ligation-free uracil-excision based technique--USER cloning--to rapidly
      construct mammalian expression vectors of multiple DNA fragments and with maximum
      flexibility, both for choice of vector backbone and cargo. The vector system
      includes a set of basic vectors and a toolbox containing a multitude of DNA
      building blocks including promoters, terminators, selectable marker- and reporter
      genes, and sequences encoding an internal ribosome entry site, cellular
      localization signals and epitope- and purification tags. Building blocks in the
      toolbox can be easily combined as they contain defined and tested Flexible
      Assembly Sequence Tags, FASTs. USER cloning with FASTs allows rapid swaps of
      gene, promoter or selection marker in existing plasmids and simple construction
      of vectors encoding proteins, which are fused to fluorescence-, purification-,
      localization-, or epitope tags. The mammalian expression vector assembly platform
      currently allows for the assembly of up to seven fragments in a single cloning
      step with correct directionality and with a cloning efficiency above 90%. The
      functionality of basic vectors for FAST assembly was tested and validated by
      transient expression of fluorescent model proteins in CHO, U-2-OS and HEK293 cell
      lines. In this test, we included many of the most common vector elements for
      heterologous gene expression in mammalian cells, in addition the system is fully
      extendable by other users. The vector system is designed to facilitate high
      throughput genome-scale studies of mammalian cells, such as the newly sequenced
      CHO cell lines, through the ability to rapidly generate high-fidelity assembly of
      customizable gene expression vectors.

PMID- 24879461
TI  - Clinical Examination and Treatment of a Leg Ulcer Caused by a Stingray Puncture.
AB  - The most frequent causes of leg ulcers include venous incompetency (superficial
      and deep), arterial insufficiency, trauma, vasculitis, and neoplasm. Leg ulcers
      from injury by stingrays are quite rare. In this case report, we describe a leg
      ulcer caused by a stingray sting complicated by infection, which healed
      completely without surgery. In addition, since there few cases in the literature
      describing such traumas, we performed a comprehensive review of the literature.
      Important is the fact that the wound healing was complete without resorting to
      surgery, but only with a correct targeted antibiotic therapy and the use of a
      collagenase, which has the particularity of having hyaluronic acid as a
      component. 

PMID- 24879462
TI  - A co-CRISPR strategy for efficient genome editing in Caenorhabditis elegans.
AB  - Genome editing based on CRISPR (clustered regularly interspaced short palindromic
      repeats)-associated nuclease (Cas9) has been successfully applied in dozens of
      diverse plant and animal species, including the nematode Caenorhabditis elegans.
      The rapid life cycle and easy access to the ovary by micro-injection make C.
      elegans an ideal organism both for applying CRISPR-Cas9 genome editing technology
      and for optimizing genome-editing protocols. Here we report efficient and
      straightforward CRISPR-Cas9 genome-editing methods for C. elegans, including a Co
      CRISPR strategy that facilitates detection of genome-editing events. We describe
      methods for detecting homologous recombination (HR) events, including direct
      screening methods as well as new selection/counterselection strategies. Our
      findings reveal a surprisingly high frequency of HR-mediated gene conversion,
      making it possible to rapidly and precisely edit the C. elegans genome both with
      and without the use of co-inserted marker genes. 

PMID- 24879464
TI  - Dating rare mutations from small samples with dense marker data.
AB  - We present a method for estimating the age of a mutation based on the genetic
      length of ancestral haplotypes shared between individuals carrying the mutation.
      The method can be reliably applied to small samples, typical of situations
      involving rare mutations, and makes effective use of modern high-density SNP
      data, thus overcoming two of the limitations with existing methods. The method
      provides age estimates and confidence intervals without the use of asymptotic
      theory and is applicable to genealogies in which the data are independent or
      correlated. In the correlated case we estimate the correlation directly from the
      data, rather than relying on a model for the genealogy. To demonstrate the
      method's efficacy, we provide simulation results and compare it to other methods.
      The length data are obtained with a simple procedure, and an R script is
      available for performing the calculations. 

PMID- 24879463
TI  - The principal role of Ku in telomere length maintenance is promotion of Est1
      association with telomeres.
AB  - Telomere length is tightly regulated in cells that express telomerase. The
      Saccharomyces cerevisiae Ku heterodimer, a DNA end-binding complex, positively
      regulates telomere length in a telomerase-dependent manner. Ku associates with
      the telomerase RNA subunit TLC1, and this association is required for TLC1
      nuclear retention. Ku-TLC1 interaction also impacts the cell-cycle-regulated
      association of the telomerase catalytic subunit Est2 to telomeres. The promotion
      of TLC1 nuclear localization and Est2 recruitment have been proposed to be the
      principal role of Ku in telomere length maintenance, but neither model has been
      directly tested. Here we study the impact of forced recruitment of Est2 to
      telomeres on telomere length in the absence of Ku's ability to bind TLC1 or DNA
      ends. We show that tethering Est2 to telomeres does not promote efficient
      telomere elongation in the absence of Ku-TLC1 interaction or DNA end binding.
      Moreover, restoration of TLC1 nuclear localization, even when combined with Est2
      recruitment, does not bypass the role of Ku. In contrast, forced recruitment of
      Est1, which has roles in telomerase recruitment and activation, to telomeres
      promotes efficient and progressive telomere elongation in the absence of Ku-TLC1
      interaction, Ku DNA end binding, or Ku altogether. Ku associates with Est1 and
      Est2 in a TLC1-dependent manner and enhances Est1 recruitment to telomeres
      independently of Est2. Together, our results unexpectedly demonstrate that the
      principal role of Ku in telomere length maintenance is to promote the association
      of Est1 with telomeres, which may in turn allow for efficient recruitment and
      activation of the telomerase holoenzyme. 

PMID- 24879465
TI  - Menadione induces the formation of reactive oxygen species and depletion of GSH
      mediated apoptosis and inhibits the FAK-mediated cell invasion.
AB  - Menadione induces apoptosis in tumor cells. However, the mechanism of apoptosis
      in ovarian cancer cells exposed to menadione is not clear. In addition, it is
      unclear whether menadione-induced apoptosis is mediated by the depletion of
      glutathione (GSH) contents that is associated with the formation of reactive
      oxygen species. Furthermore, the effect of menadione on the invasion and
      migration of human epithelial ovarian cancer cells has not been studied.
      Therefore, we investigated the effects of menadione exposure on apoptosis, cell
      adhesion, and cell migration using the human epithelial ovarian carcinoma cell
      lines OVCAR-3 and SK-OV-3. The results suggest that menadione may induce
      apoptotic cell death in ovarian carcinoma cell lines by activating the
      mitochondrial pathway and the caspase-8- and Bid-dependent pathways. The
      apoptotic effect of menadione appears to be mediated by the formation of reactive
      oxygen species and the depletion of GSH. Menadione inhibited fetal-bovine-serum
      induced cell adhesion and migration of OVCAR-3 cells, possibly through the
      suppression the focal adhesion kinase (FAK)-dependent activation of cytoskeletal
      associated components. Therefore, menadione might be beneficial in the treatment
      of epithelial ovarian adenocarcinoma and combination therapy. 

PMID- 24879467
TI  - N[1,3]-Sigmatropic shift in the benzidine rearrangement: experimental and
      theoretical investigation.
AB  - The N[1,3]-sigmatropic shift in the benzidine rearrangement has been studied in
      depth experimentally with the aid of density functional theory (DFT)
      calculations. The designed substituted N,N'-diaryl hydrazines rearrange
      exclusively to the expected o/p-semidines and diphenylines. Intercrossing
      experiments support the intramolecular rearrangement process. Radical trapping
      experiments exclude the intermediacy of biradicals in the rearrangements.
      Computational results demonstrate that the o-semidine rearrangement involves a
      novel N[1,3]-sigmatropic shift and the p-semidine rearrangement proceeds via
      tandem N[1,3]/N[1,3]-sigmatropic shifts, while the diphenyline rearrangement
      occurs through cascade N[1,3]/[3,3]-sigmatropic shifts. The proposed mechanism
      involving the key N[1,3]-sigmatropic shift as the rate-limiting step is in good
      agreement with reported kinetic isotope measurements. The combined methods
      provide new insight into the formation mechanism of o/p-semidines and
      diphenylines in the benzidine rearrangement and support the unprecedented
      suprafacial symmetry allowed N[1,3]-sigmatropic shift with an inversion of the
      configuration in the migrating nitrogen atom. 

PMID- 24879466
TI  - Fluorescent dye labeled iron oxide/silica core/shell nanoparticle as a multimodal
      imaging probe.
AB  - PURPOSE: To develop an MRI/optical multimodal imaging probe based on dye
      conjugated iron oxide/silica core/shell nanoparticle, and investigate the
      distance-dependent fluorescence quenching through careful control of the distance
      between the iron oxide core and fluorescent dyes. METHODS: Different size of
      core/shell nanoparticles were prepared by varying the silica shell width.
      PEGylation on the surface of silica shell was followed to improve the stability
      of particles in the physiological condition. In vitro cytotoxicity was evaluated
      by the MTT assay on a HeLa cell line and in vivo imaging of subcutaneous SCC7
      xenografted mice was performed using MRI/optical imaging modalities. RESULTS:
      Diameter and zeta-potential of the nanoparticles were measured, and TEM images
      demonstrated the mono-disperse nature of the particles. Quenching efficiency of
      the dyes on the surface was nearly 100% in the smallest nanoparticle, while
      almost no quenching effect was observed for the largest nanoparticle. In vitro
      cytotoxicity showed nearly 90% cell viability at 0.15 Fe mg/mL, a comparable
      concentration for clinical use. The tumor area was significantly darkened after
      the nanoparticle injection due to the high transverse relaxivity value of the
      nanoparticles. Fluorescence signal was affected by the particle size due to the
      distance-dependent quenching/dequenching behaviour.

PMID- 24879468
TI  - Systemic Therapy in Advanced Cutaneous Squamous Cell Carcinoma (CSCC): The
      Roswell Park Experience and a Review of the Literature.
AB  - OBJECTIVES: Treatment of locally advanced unresectable or metastatic cutaneous
      squamous cell carcinoma (mCSCC) is suboptimal with a paucity of robust data on
      systemic therapy. This retrospective study aimed to evaluate the efficacy and
      outcomes of patients with locally advanced unresectable or mCSCC treated with
      systemic therapy. METHODS: Records of patients with CSCC treated with systemic
      therapy from January 2001 to January 2011 were reviewed. Response was assessed
      using WHO criteria. Descriptive results were assessed using Wilcoxon rank-sum
      test for ordinal responses and Pearson chi test for categorical responses.
      Survival was calculated by the Kaplan-Meier method. RESULTS: Of 28 patients
      identified, 25 patients (M:F=18:7), median age 66 years (range, 39 to 85 y), had
      the required data for final analysis. Partial response was 44% and stable disease
      (SD) was 24%. The median progression-free survival (PFS) and overall survival
      (OS) were 5.5 months (2.3, 13.2) and 10.9 months (5.3, 21.3) respectively; 3-year
      OS was 22%. Patients with WHO response had improved PFS (20.8 mo; 4.4, NR) and OS
      (37.5 mo; 10.3, NR) compared with patients with SD/PD (PFS 2.7 mo; OS 5.9 mo).
      Use of platinum-based therapy significantly improved PFS and OS, whereas taxanes
      and cetuximab had no impact in this small cohort. There was no difference in PFS
      or OS with multiagent versus single-agent therapy. CONCLUSIONS: Platinum-based
      therapy remains as one of the standard options in advanced CSCC management.
      Agents to improve response rates are needed and future trials should address the
      use of novel targeted and new chemotherapy combinations in CSCC.

PMID- 24879470
TI  - Management of Unplanned Excision for Soft-Tissue Sarcoma With Preoperative
      Radiotherapy Followed by Definitive Resection.
AB  - BACKGROUND AND OBJECTIVES: The purpose of this study was to review the outcomes
      after preoperative radiotherapy and definitive surgery for patients who initially
      had inadvertent excision for sarcoma. MATERIALS AND METHODS: Treatment records of
      44 consecutive patients, who initially underwent unplanned excision of soft
      tissue sarcoma between January 2004 and January 2012, were reviewed. All patients
      had clinically localized disease before treatment and received preoperative
      external-beam radiotherapy followed by definitive oncologic surgery at our
      institution. RESULTS: The median follow-up was 36 months. Residual tumor after
      preoperative radiotherapy and wound bed excision was identified in 39% (17/44) of
      the cases. Kaplan-Meier estimates for 5-year local control, recurrence-free
      survival, and overall survival are 95% (95% confidence interval [CI], 80-99), 86%
      (95% CI, 69-94), and 94% (95% CI, 79-99) respectively. Perioperative morbidity
      occurred in 25% of patients (11/44.) All patients with perioperative wound
      complications had lower extremity sarcomas. CONCLUSIONS: Optimal management for
      unplanned excision of soft-tissue sarcoma is unknown. Our institution has adopted
      the approach of preoperative radiotherapy, followed by definitive surgery. In our
      series of 44 patients, local control was excellent at 95%, with perioperative
      complications seen only in patients with lower extremity sarcomas, suggesting
      that this is a reasonable approach to manage inadvertently resected sarcoma.

PMID- 24879469
TI  - Long-term Treatment Outcomes for Locally Advanced Esophageal Cancer: A Single
      Institution Experience.
AB  - OBJECTIVES: To determine long-term outcomes in patients with locally advanced
      esophageal carcinoma treated with trimodality therapy (chemoradiotherapy [CRT]
      and surgery, TMT) or definitive CRT. METHODS: We retrospectively identified
      patients with advanced esophageal carcinoma treated with curative intent at our
      institution between 1998 and 2004. Identified patients were separated into 3
      groups: patients who received TMT, patients who received CRT, and patients who
      began treatment with trimodality intent but did not undergo surgery (PTMT). Local
      control, overall survival (OS), and distant metastasis-free survival were
      compared using Kaplan-Meier statistics. RESULTS: Among the 265 patients included,
      median follow-up was 6.4 years for surviving patients and 1.7 years for all
      patients. Type of esophageal cancer was adenocarcinoma in 213 patients (80%) and
      squamous cell carcinoma in 46 patients (17%). Treatment groups comprised 169
      patients (64%) completing TMT, 46 patients medically unable to undergo surgery
      after neoadjuvant therapy (PTMT), and 50 (19%) who underwent CRT. Median OS was
      20.5 months; actuarial 5- and 10-year OS were 27% and 12%, respectively. The TMT
      group had the highest 5- and 10-year OS (32% and 19%, respectively). Local
      control rates at 2, 5, and 10 years for all patients were 80%, 70%, and 69%,
      respectively. By treatment modality, 5-year local control was best (82%) for TMT,
      compared with 60% for CRT and 40% for PTMT groups (P<0.001). CONCLUSIONS:
      Patients who completed TMT had the best local control and long-term OS. In the
      context of TMT, surgery seemed more beneficial in patients with esophageal
      adenocarcinoma versus squamous cell carcinoma.

PMID- 24879471
TI  - Outcomes After Curative Thoracic Radiotherapy in Patients With Coronary Artery
      Disease and Existing Cardiac Stents.
AB  - OBJECTIVES: To evaluate outcomes among cancer patients with preexisting coronary
      artery disease and cardiac stenting who subsequently underwent thoracic
      radiotherapy (RT). METHODS: From 1998 to 2012, 147 patients received percutaneous
      coronary intervention (PCI) and then curative external beam RT (>30 Gy, except
      for Hodgkin lymphoma patients) involving the heart and the lungs. Heart-specific
      and lung-specific dosimetric parameters were correlated to overall survival (OS)
      and cardiac-specific survival by Cox variate methods. RESULTS: The mean interval
      between PCI and cancer diagnosis was 1.8 years (range, 0.1 to 14.2 y).
      Hypertension was present in 105 patients (71%), and hyperlipidemia in 82 (56%).
      At the time of analysis, 69 patients (47%) were alive, 3 (2%) died of cardiac
      causes, and 53 (36%) died of cancer. In multivariate analyses, OS since PCI was
      related to cancer type (P=0.004). Decreased OS since cancer diagnosis was related
      to older age (P<0.001) and increased percentage of targeted volume or organ
      receiving 20 Gy or more for lung (P<0.001), even after controlling for sex,
      cancer type, and stage. However, for non-cancer-specific survival and major
      adverse cardiac event-free survival, older age and underlying cardiopulmonary
      comorbidities dominated (rather than heart and lung dosimetric parameters) in
      predicting worse outcome for these patients with preexisting coronary artery
      disease who later underwent RT. CONCLUSIONS: Cancer type, older age, and
      preexisting cardiopulmonary comorbidities and risk factors most significantly
      predicted clinical outcome and survival for these patients with existing coronary
      stents who subsequently received thoracic RT. Dosimetric detrimental effects were
      not significant in our study.

PMID- 24879472
TI  - The Impact of Perioperative Chemotherapy Timing in Conjunction With Postoperative
      External-Beam Radiation Therapy on Extremity Soft-Tissue Sarcomas Outcome.
AB  - PURPOSE: The perioperative management of primary extremity soft-tissue sarcomas
      (ESTS) is multidisciplinary including radiation therapy and chemotherapy (CT).
      The interplay between these modalities and the relative importance of each remain
      unclear. Our study aims to determine the relative impact of CT and radiotherapy
      on the outcome of ESTS patients treated with limb-sparing surgery. MATERIALS AND
      METHODS: A retrospective review of ESTS registry yielded 97 patients who received
      neoadjuvant chemotherapy (NCT) and/or adjuvant CT with or without external-beam
      radiation therapy (EBRT) from January 1, 1999 through December 31, 2009. The
      cohort comprised 56 males and 41 females whose age at surgery ranged from 17 to
      83 years (median, 56 y). Tumor characteristics included the following: 73 lower
      ESTS; 70 grade 3 lesions; 63 American Joint Committee on Cancer stage III tumors;
      and 27 lesions with positive microscopic margins. The following outcome
      parameters were evaluated for the patients' subgroups: overall survival (OS),
      locoregional control (LRC), and disease-free survival (DFS). RESULTS: EBRT was
      delivered postoperatively to 81 patients and 49 received CT. Median EBRT dose was
      63 Gy (range, 50 to 72 Gy). At median follow-up of 54.6 months, the 5-year OS,
      LRC, DFS was 68.9%, 87.1%, 66.5%, respectively. On multivariate analysis,
      positive surgical margins negatively impacted LRC, DFS, and OS (hazard ratio
      [HR]=10.43, P=0.004), (HR=2.37, P=0.03), (HR=2.26, P=0.038), respectively. EBRT
      use improved LRC (HR=0.24, P=0.018) and DFS (HR=0.36, P=0.021). The impact of
      EBRT on DFS was retained (HR=0.28, P=0.006) in the high-grade ESTS subgroup who
      received CT. The 5-year local failure rate was 6.5%, 28.6%, and 22.2% (P=0.019)
      for patient receiving NCT, adjuvant chemotherapy, and no CT, respectively.
      CONCLUSION: Our data support the use of NCT followed by limb-sparing surgery and
      adjuvant EBRT in ESTS for local failure reduction with a trend toward improved
      DFS.

PMID- 24879473
TI  - Do Sociodemographic Factors Influence Outcome in Prostate Cancer Patients Treated
      With External Beam Radiation Therapy?
AB  - OBJECTIVES: The purpose of this study was to analyze the prognostic significance
      of sociodemographic factors on biochemical control (bNED) and overall survival
      (OS) in patients with prostate cancer. METHODS: Prostate cancer patients treated
      with definitive external beam radiation therapy (EBRT)+/-hormone therapy from
      1997 to 2006 were analyzed in this IRB-approved study. Patient demographics,
      treatment (Tx), and clinical outcome were obtained from electronic medical
      records. Median household income (mHHI) at the census block group level was
      obtained from the 2000 census data. Data on disease and Tx parameters included
      Gleason score, pre-Tx prostate-specific antigen (PSA), T stage, year of Tx, EBRT
      dose, and use of hormone therapy. Patients were categorized as having low-risk,
      intermediate-risk, or high-risk disease. Sociodemographic factors included age,
      race, marital status, and mHHI. Biochemical failure was defined as nadir PSA+2
      ng/mL. OS was based on death from any cause. RESULTS: A total of 788 consecutive
      patients were studied with a median follow-up of 7 years (range, 0.4 to 15 y).
      African Americans comprised 48% of the patients, whereas 46% of patients were
      white and 6% were other races. Whites had an average mHHI of $60,190 compared
      with $36,917 for African Americans (P<0.001). After multivariable modeling, only
      radiation dose was predictive for bNED (P=0.004) or OS (P=0.008). No
      sociodemographic factors were predictive for either outcome. Higher radiation
      dose predicted for better biochemical control and OS. CONCLUSIONS: This analysis
      suggests that sociodemographic factors are not important prognostic factors in
      determining outcome after EBRT for prostate cancer.

PMID- 24879474
TI  - Stereotactic Body Radiotherapy for Elderly Patients With Medically Inoperable
      Pancreatic Cancer.
AB  - OBJECTIVES: People over the age of 75 years account for approximately 40% of
      patients diagnosed with pancreatic cancer, many with comorbidities that may limit
      their treatment options. This study reports on the use of stereotactic body
      radiation therapy (SBRT) in this population. MATERIALS AND METHODS: Twenty
      consecutively treated patients over the age of 75 with pathologically proven
      localized pancreatic cancer were included in this retrospective review. All had
      been evaluated by a multidisciplinary team as unable to tolerate surgery or
      combined chemoradiation therapy. Patient outcomes were analyzed to determine the
      safety and efficacy of SBRT in this elderly cohort. RESULTS: The median age was
      83.2 years (minimum 77 y, maximum 90 y). Eighteen patients were treated at time
      of initial diagnosis, and 2 for recurrence after surgery. Eleven (55%) of the
      patients had an Adult Comorbidity Evaluation-27 comorbidity index score of 3
      (severe) and 6 (30%) had a score of 2 (moderate). Fourteen patients were treated
      with 35 Gy in 5 fractions, 5 with 30 Gy in 5 fractions, and 1 patient with 36 Gy
      in 3 fractions. Seven (35%) patients had common terminology criteria for adverse
      events (CTCAE) V4.0 toxicity grade of 1-2, and 3 patients had a CTCAE V4.0
      toxicity grade of 3-4, 2 with dehydration, and 1 had episodes of gastrointestinal
      bleeding. Three patients recurred locally, 10 had distant metastases, 4 of whom
      were found on the first posttreatment scan. Median overall survival was 6.4
      months (95% confidence interval, 3.5-10.8 mo). Median recurrence-free survival
      was 6.8 months (95% confidence interval, 1.3-23.5 mo). Two patients survived >23
      months. CONCLUSION: SBRT for pancreatic cancer appears to be a safe and effective
      method for treatment of elderly patients, even in the setting of severe
      comorbidities.

PMID- 24879475
TI  - Trend in Age and Racial Disparities in the Receipt of Postlumpectomy Radiation
      Therapy for Stage I Breast Cancer: 2004-2009.
AB  - OBJECTIVES: Significant effort has been expended over the past decade to reduce
      racial disparities in breast cancer care. Whether disparities in receipt of
      appropriate radiotherapy care for breast cancer persisted despite these efforts
      is unknown, as is the impact of being eligible for Medicare. We therefore
      investigated trends in racial differences by age in postbreast lumpectomy
      radiation therapy (PLRT) from 2004 to 2009. MATERIALS AND METHODS: We analyzed
      the Surveillance, Epidemiology and End Results registry database for women aged
      40 to 85 years who underwent lumpectomy for stage I breast cancer and were
      eligible for PLRT. We examined variables potentially associated with the receipt
      of PLRT, including year of diagnosis, race, and examined women separately by age
      group. RESULTS: Among 67,124 women aged 40 to 85 years undergoing lumpectomy,
      receipt of PLRT decreased from 80.7% in 2004 to 76.8% by 2009 (P<0.001). There
      remained a persistent disparity in PLRT among African American women (in 2004,
      80.6% white vs. 78.9% African American and in 2009, 77.5% white vs. 72.0% African
      American). In multivariable logistic regression, African American race (odds
      ratio [OR], 0.82; 95% confidence interval [CI]. 0.76-0.89) and being diagnosed
      more recently were associated with lower odds of PLRT (OR for 2009 vs. 2004:
      0.74; 95% CI, 0.69-0.79), whereas older women typically covered by public health
      insurance (aged 65 to 69 y) were more likely to receive PLRT (OR, 1.09; 95% CI,
      1.02-1.15). CONCLUSIONS: PLRT decreased by a significant percentage of 3.9% among
      all women in recent years, and racial disparities in PLRT receipt have persisted.
      Medicare eligibility increased the likelihood of PLRT receipt.

PMID- 24879476
TI  - Asian Versus Non-Asian Outcomes in Nasopharyngeal Carcinoma: A North American
      Population-based Analysis.
AB  - OBJECTIVES: The effect of ethnicity on nasopharyngeal cancer (NPC) outcomes is
      unclear. This retrospective analysis examines survival and the impact of
      concurrent chemoradiation (chemoRT) among Asian and non-Asian patients. METHODS:
      Subjects included 380 consecutive patients with NPC treated at a Canadian
      institution from 2000 to 2009. Five-year Kaplan-Meier progression-free survival
      (PFS), disease-specific survival (DSS), and overall survival (OS) were compared
      between Asian (n=279) and non-Asian (n=101) subjects. Multivariable analysis was
      performed using Cox regression modeling. Two-variable interaction terms with
      concurrent chemoRT were used to examine whether concurrent chemoRT conferred
      different effects among subgroups. RESULTS: Asian subjects presented with earlier
      stage (P=0.005), were younger, had better performance status, and were less
      likely smokers (all P<0.001). Survival among Asian versus non-Asian subjects with
      stage I/II NPC were: PFS 68% versus 59% (P=0.04), DSS 87% versus 77% (P=0.08),
      and OS 84% versus 74% (P=0.003). Corresponding rates with stage III/IVA/IVB
      disease were PFS 49% versus 42% (P=0.12), DSS 72% versus 46% (P=0.001), and OS
      70% versus 44% (P<0.001). On multivariable analysis, Asian ethnicity, age below
      65 years, ECOG performance status 0-1, early stage, staging MRI use, and
      concurrent chemoRT were associated with improved DSS and OS (P<0.05). On testing
      interactions with concurrent chemoRT, Asian versus non-Asian ethnicity was
      significant (hazard ratio 3.9), suggesting that concurrent chemoRT conferred more
      benefit among non-Asian compared with Asian subjects. CONCLUSIONS: In this
      population-based study, Asian ethnicity was associated with improved DSS and OS.
      Concurrent chemoRT conferred more benefit among non-Asian compared with Asian
      subjects.

PMID- 24879477
TI  - Interdependence of the actin and the microtubule cytoskeleton during fungal
      growth.
AB  - Cell polarization is a theme in biology conserved from bacteria to man. One of
      the most extremely polarized cells in nature is the hyphae of filamentous fungi.
      A continuous flow of secretion vesicles from the hyphal cell body to the tip is
      essential for cell wall and membrane extension. Microtubules (MTs) and actin,
      along with their corresponding motor proteins, are involved in the secretion
      process. Therefore, the arrangement of the cytoskeleton is a crucial step to
      establish and maintain polarity. Here we review recent findings unraveling the
      mechanism of polarized growth with special emphasis on the role of the actin and
      MT cytoskeletons and cell end markers linking the two cytoskeletons. We will
      mainly focus on Neurospora crassa and Aspergillus nidulans as model organisms. 

PMID- 24879478
TI  - Fungal pathogens are platforms for discovering novel and conserved septin
      properties.
AB  - Septins are filament-forming GTP-binding proteins that act as scaffolds in
      diverse cell functions including division, polarity and membrane remodeling. In a
      variety of fungal pathogens, it has been observed that septins are required for
      virulence because cells are unable to survive or are misshapen when septins are
      mutated. Cell morphology is interconnected with pathogenesis and thus septin
      mutants displaying aberrant cell morphologies are commonly deficient in host
      tissue invasion. The degree to which septins orchestrate versus maintain changes
      in fungal cell morphology during pathogenesis remains to be determined. Aside
      from the importance of septins in the process of pathogenesis, animal and plant
      fungal pathogens display complexity in septin form, dynamics, and function not
      seen in Saccharomyces cerevisiae making these organisms important models for
      uncovering diversity in septin behavior. Additionally, host septins have recently
      been implicated in the process of Candida albicans invasion, motivating the need
      to examine host septins in fungal pathogenesis. Understanding the role of septins
      in the host-pathogen interaction not only illuminates pathogenesis mechanisms but
      importantly also expands our understanding of septin biology in general. 

PMID- 24879479
TI  - Protein-protein interaction network of the marine microalga Tetraselmis
      subcordiformis: prediction and application for starch metabolism analysis.
AB  - Under stressful conditions, the non-model marine microalga Tetraselmis
      subcordiformis can accumulate a substantial amount of starch, making it a
      potential feedstock for the production of fuel ethanol. Investigating the
      interactions of the enzymes and the regulatory factors involved in starch
      metabolism will provide potential genetic manipulation targets for optimising the
      starch productivity of T. subcordiformis. For this reason, the proteome of T.
      subcordiformis was utilised to predict the first protein-protein interaction
      (PPI) network for this marine alga based on orthologous interactions, mainly from
      the general PPI repositories. Different methods were introduced to evaluate the
      credibility of the predicted interactome, including the confidence value of each
      PPI pair and Pfam-based and subcellular location-based enrichment analysis.
      Functional subnetworks analysis suggested that the two enzymes involved in starch
      metabolism, starch phosphorylase and trehalose-phosphate synthase may be the
      potential ideal genetic engineering targets. 

PMID- 24879480
TI  - Improving the thermostability of a mesophilic family 10 xylanase, AuXyn10A, from
      Aspergillus usamii by in silico design.
AB  - To improve the thermostability of a mesophilic GH family 10 xylanase, AuXyn10A,
      from Aspergillus usamii E001, its modification was performed by in silico design.
      Based on the comparison of B-factor values, a mutant xylanase ATXyn10 was
      predicted by substituting a segment YP from Tyr(25) to Pro(34) of AuXyn10A with
      the corresponding one from Asn(24) to Ala(32) of TaXyn10, a thermophilic GH
      family 10 xylanase from Thermoascus aurantiacus. Analysis of a TaXyn10 crystal
      structure indicated that there is a close interaction between segments YP and FP.
      For that reason, another mutant xylanase ATXyn10(M) was designed by mutating
      Ser(286) and His(288) of ATXyn10 into the corresponding Gly(285) and Phe(287) in
      the FP of TaXyn10. Then, two ATXyn10- and ATXyn10(M)-encoding genes, ATxyn10 and
      ATxyn10 (M), were expressed in Pichia pas toris GS115. The temperature optimum of
      recombinant (re) ATXyn10(M) was 60  degrees C, 10  degrees C higher than that of
      reAuXyn10A. Its thermal inactivation half-life (t(1/2)) at 55  degrees C was 10.4
      fold longer than that of reAuXyn10A. As compared with reAuXyn10A, reATXyn10(M)
      displayed a slight decrease in K(m) value and a significant increase in V(max)
      value from 6,267 to 8,870 U/mg.

PMID- 24879481
TI  - Characterization of acetoin production in a budC gene disrupted mutant of
      Serratia marcescens G12.
AB  - The 2,3-butanediol (2,3-BD) dehydrogenase gene budC of Serratia marcescens G12
      was disrupted to construct the acetoin (AC) producing strain G12M. In shake-flask
      cultures, AC production was enhanced by increased concentrations of glucose or
      sodium acetate in G12M. In fed-batch fermentation, G12M produced 47.5 g/L AC
      along with 9.8 g/L 2,3-BD. The expression of the key enzymes for AC synthesis was
      further investigated. Alpha-acetolactate synthase gene budB decreased its
      expression significantly in G12M compared with G12. This probably explained the
      moderate AC production in G12M cultures. Additionally, overexpression of budB
      gene and alpha-acetolactate decarboxylase gene budA was conducted in G12M and no
      significant increase of AC was observed. The results suggested that intracellular
      AC accumulation might inhibit the expression of budB and budA gene and induce
      budC gene expression in G12M. Our analyses offered the bases for further genetic
      manipulations in improving AC production in microbial fermentations.

PMID- 24879483
TI  - Identification of known chemicals and their metabolites from Alpinia oxyphylla
      fruit extract in rat plasma using liquid chromatography/tandem mass spectrometry
      (LC-MS/MS) with selected reaction monitoring.
AB  - Alpinia oxyphylla (Yizhi) capsularfruits are commonly used in traditional
      medicine. Pharmacological studies have demonstrated that A. oxyphylla
      capsularfruits have some beneficial roles. Besides volatile oil, sesquiterpenes,
      diarylheptanoids and flavonoids are main bioactive constituents occurring in the
      Yizhi capsularfruits. The representative constituents include tectochrysin,
      izalpinin, chrysin, apigenin-4',7-dimethylether, kaempferide, yakuchinone A,
      yakuchinone B, oxyphyllacinol and nootkatone. Their content levels in the fruit
      and its pharmaceutical preparations have been reported by our group. The nine
      phytochemicals are also the major components present in the Yizhi alcoholic
      extracts, which have anti-diarrheal activities. However, the fates of these
      constituents in the body after oral or intravenous administration remain largely
      unknown. In the present study, we focus on these phytochemicals albeit other
      concomitant compounds. The chemicals and their metabolites in rat plasma were
      identified using liquid chromatography/tandem mass spectrometry with selected
      reaction monitoring mode after orally administered Yizhi extract to rats. Rat
      plasma samples were treated by methanol precipitation, acidic or enzymatic
      hydrolysis. This target analysis study revealed that: (1) low or trace plasma
      levels of parent chemicals were measured after p.o. administration of Yizhi
      extract, Suoquan capsules and pills to rats; (2) flavonoids and diarylheptanoids
      formed mainly monoglucuronide metabolites; however, diglucuronide metabolites for
      chrysin, izalpinin and kaempferide were also detected; (3) metabolic reduction of
      Yizhi diarylheptanoids occurred in rats. Yakuchinone B was reduced to yakuchinone
      A and then to oxyphyllacinol in a stepwise manner and subsequently glucuronidated
      by UDP-glucuronosyl transferase. Further research is needed to characterize the
      UDP-glucuronosyl transferase and reductase involved in the biotransformation of
      Yizhi chemicals. 

PMID- 24879482
TI  - Production of kaempferol 3-O-rhamnoside from glucose using engineered Escherichia
      coli.
AB  - Flavonoids are ubiquitous phenolic compounds and at least 9,000 have been
      isolated from plants. Most flavonoids have been isolated and assessed in terms of
      their biological activities. Microorganisms such as Escherichia coli and
      Saccharomyces cerevisiae are efficient systems for the synthesis of flavonoids.
      Kaempferol 3-O-rhamnoside has notable biological activities such as the
      inhibition of the proliferation of breast cancer cells, the absorption of glucose
      in the intestines, and the inhibition of the self-assembly of beta amyloids. We
      attempted to synthesize kaempferol 3-O-rhamnoside from glucose in E. coli. Five
      flavonoid biosynthetic genes [tyrosine ammonia lyase (TAL), 4-coumaroyl CoA
      ligase (4CL), chalcone synthase (CHS), flavonol synthase (FLS), and flavonol 3-O
      rhamnosyltransferase (UGT78D1)] from tyrosine were introduced into E. coli that
      was engineered to increase tyrosine production. By using this approach, the
      production of kaempferol 3-O-rhamnoside increased to 57 mg/L.

PMID- 24879484
TI  - Interleukin-21 polymorphism affects gene expression and is associated with risk
      of ischemic stroke.
AB  - There has been more and more evidence to confirm the essential role of
      inflammatory processes in the development of ischemic stroke. Interleukin-21 (IL
      21), the most recently discovered CD132-dependent cytokine, plays a key role in
      regulating inflammation. The aim of the study was to understand the association
      between IL-21 polymorphisms and ischemic stroke, and the effects of these
      polymorphisms on gene expression. Two polymorphisms in IL-21, rs907715G/A and
      rs4833837A/G, were identified in 278 ischemic stroke patients and 282 healthy
      controls. Results showed that frequencies of rs907715GA and AA genotypes were
      significantly increased in cases than in controls (odd ratio (OR) = 1.49, 95%
      confidence interval (CI): 1.01-2.14, P = 0.042; OR = 2.21, 95% CI: 1.38-3.53, P =
      0.001). Similarly, rs907715A allele revealed a positive association with the
      disease (OR = 1.52, P = 0.001). The rs4833837A/G polymorphism did not show any
      correlation with ischemic stroke. We further evaluated IL-21 messenger RNA (mRNA)
      and protein levels in peripheral blood mononuclear cells (PBMCs) from subjects
      carrying different polymorphism genotypes. Results revealed that subjects
      carrying polymorphic rs907715GA and AA genotypes had significantly higher IL-21
      mRNA levels, whereas protein level was increased only in subjects with rs907715AA
      genotype. Serum level of IL-21 was also significantly elevated in subjects with
      rs907715AA genotype. These data suggest that IL-21 polymorphism is associated
      with increased susceptibility to ischemic stroke possibly by upregulating gene
      expression.

PMID- 24879485
TI  - Evaluation of the relationship between the Adenosine Triphosphate (ATP)
      bioluminescence assay and the presence of Bacillus anthracis spores and
      vegetative cells.
AB  - BACKGROUND: The Adenosine triphosphate (ATP) bioluminescence assay was utilized
      in laboratory evaluations to determine the presence and concentration of
      vegetative and spore forms of Bacillus anthracis Sterne 34F2. METHODS: Seventeen
      surfaces from the healthcare environment were selected for evaluation. Surfaces
      were inoculated with 50 uL of organism suspensions at three concentrations of
      104, 106, 108 colony forming units per surface (CFU/surface) of B. anthracis.
      Culture-based methods and ATP based methods were utilized to determine
      concentrations. RESULTS: When all concentrations were evaluated together, a
      positive correlation between log-adjusted CFU and Relative Light Units (RLU) for
      endospores and vegetative cells was established. When concentrations were
      evaluated separately, a significant correlation was not demonstrated.
      CONCLUSIONS: This study demonstrated a positive correlation for ATP and culture
      based methods for the vegetative cells of B. anthracis. When evaluating the
      endospores and combining both metabolic states, the ATP measurements and CFU
      recovered did not correspond to the initial concentrations on the evaluated
      surfaces. The results of our study show that the low ATP signal which does not
      correlate well to the CFU results would not make the ATP measuring devises
      effective in confirming contamination residual from a bioterrorist event.

PMID- 24879487
TI  - Is hunting still healthy? Understanding the interrelationships between indigenous
      participation in land-based practices and human-environmental health.
AB  - Indigenous participation in land-based practices such as hunting, fishing,
      ceremony, and land care has a long history. In recent years, researchers and
      policy makers have advocated the benefits of these practices for both Indigenous
      people and the places they live. However, there have also been documented risks
      associated with participation in these activities. Environmental change brought
      about by shifts in land use, climate changes, and the accumulation of
      contaminants in the food chain sit alongside equally rapid shifts in social,
      economic and cultural circumstances, preferences and practices. To date, the
      literature has not offered a wide-ranging review of the available cross
      disciplinary or cross-ecozone evidence for these intersecting benefits and risks,
      for both human and environmental health and wellbeing. By utilising hunting as a
      case study, this paper seeks to fill part of that gap through a transdisciplinary
      meta-analysis of the international literature exploring the ways in which
      Indigenous participation in land-based practices and human-environmental health
      have been studied, where the current gaps are, and how these findings could be
      used to inform research and policy. The result is an intriguing summary of
      disparate research that highlights the patchwork of contradictory understandings,
      and uneven regional emphasis, that have been documented. A new model was
      subsequently developed that facilitates a more in-depth consideration of these
      complex issues within local-global scale considerations. These findings challenge
      the bounded disciplinary and geographic spaces in which much of this work has
      occurred to date, and opens a dialogue to consider the importance of approaching
      these issues holistically. 

PMID- 24879488
TI  - Assessing alcohol dependence in hospitalized patients.
AB  - Alcohol misuse is generally not detected in hospital settings. The goal of this
      study was to estimate the prevalence of alcohol abuse and dependence in
      hospitalized patients in a university hospital in Sao Paulo (Brazil). Patients
      were randomly selected from all hospital admissions. The final sample consisted
      of 169 adult inpatients. Two screening tools were used: the Short Alcohol
      Dependence Data (SADD) and the CAGE questionnaires. In this sample, 25.4% of
      patients could be considered alcohol dependent according to the CAGE
      questionnaire, whereas 32.9% of patients fulfilled the criteria according to the
      SADD. The only predictor of alcohol dependence was gender; male inpatients were
      3.2 times more prone to alcohol dependence with female inpatients. All inpatients
      should be systematically screened for alcohol use disorders. The choice of the
      screening tool will depend on whether the goal is to identify inpatients with
      hazardous drinking behaviors or with established alcohol-related problems. To
      maximize proper case identification, the CAGE questionnaire should be used as a
      first-step screening tool, and patients who screen positive on this scale should
      be subsequently administered the SADD questionnaire to assess the severity of the
      condition. 

PMID- 24879486
TI  - Engineered nanomaterials in food: implications for food safety and consumer
      health.
AB  - From the current state-of-the-art, it is clear that nanotechnology applications
      are expected to bring a range of benefits to the food sector aiming at providing
      better quality and conservation. In the meantime, a growing number of studies
      indicate that the exposure to certain engineered nanomaterials (ENMs) has a
      potential to lead to health complications and that there is a need for further
      investigations in order to unravel the biological outcomes of nanofood
      consumption. In the current review, we summarize the existing data on the
      (potential) use of ENMs in the food industry, information on the toxicity
      profiles of the commonly applied ENMs, such as metal (oxide) nanoparticles (NPs),
      address the potential food safety implications and health hazards connected with
      the consumption of nanofood. A number of health complications connected with the
      human exposure to ENMs are discussed, demonstrating that there is a real basis
      for the arisen concern not only connected with the gut health, but also with the
      potency to lead to systemic toxicity. The toxicological nature of hazard,
      exposure levels and risk to consumers from nanotechnology-derived food are on the
      earliest stage of investigation and this review also highlights the major gaps
      that need further research and regulation. 

PMID- 24879489
TI  - Global research on smoking and pregnancy-a scientometric and gender analysis.
AB  - The exposure to tobacco smoke during pregnancy is considered to be amongst the
      most harmful avoidable risk factors. In this scientometric and gender study
      scientific data on smoking and pregnancy was analyzed using a variety of
      objective scientometric methods like the number of scientific contributions, the
      number of citations and the modified h-index in combination with gender-specific
      investigations. Covering a time period from 1900 to 2012, publishing activities
      of 27,955 authors, institutions and countries, reception within the international
      scientific community and its reactions were analyzed and interpreted. Out of
      10,043 publications the highest number of scientific works were published in the
      USA (35.5%), followed by the UK (9.9%) and Canada (5.3%). These nations also
      achieve the highest modified h-indices of 128, 79 and 62 and the highest citation
      rates of 41.4%, 8.6% and 5.3%, respectively. Out of 12,596 scientists 6,935 are
      female (55.1%), however they account for no more than 49.7% of publications
      (12,470) and 42.8% of citations (172,733). The highest percentage of female
      experts about smoking and pregnancy is found in Australasia (60.7%), while the
      lowest is found in Asia (41.9%). The findings of the study indicate an increase
      in gender equality as well as in quantity and quality of international scientific
      research about smoking and pregnancy in the future. 

PMID- 24879490
TI  - Association between orthostatic hypotension and cardiovascular risk,
      cerebrovascular risk, cognitive decline and falls as well as overall mortality: a
      systematic review and meta-analysis.
AB  - OBJECTIVE: Several studies have suggested that orthostatic hypotension may be an
      independent predictor of cardiovascular or cerebrovascular risk and all-cause
      mortality, particularly in a geriatric population. In 1996, a consensus defined
      orthostatic hypotension as a SBP fall at least 20 mmHg and/or a DBP fall at least
      10 mmHg within 3 min of standing. METHODS: Pubmed and Cochrane database were
      searched up to October 2013 in order to identify prospective studies evaluating,
      in adult populations, the association between orthostatic hypotension as defined
      by the 1996 consensus and clinical outcome. Meta-regression was performed when
      sufficient data were available. RESULTS: A total of 28 prospective studies were
      found eligible for inclusion in this systematic review. Nine prospective studies
      found an association between orthostatic hypotension and various cardiovascular
      events such as coronary disease, heart failure, and arrhythmias. No association
      was found between orthostatic hypotension and the risk for strokes and falls in
      the majority of the prospective included studies. Insufficient data were
      available to perform a meta-analysis for strokes and falls. The meta-analysis of
      seven prospective studies found that orthostatic hypotension is associated with a
      significant increased risk for overall mortality [pooled hazard ratio in random
      effects model = 1.36 (1.13-1.63), P < 0.001)]. CONCLUSION: This meta-analysis
      provides evidence that orthostatic hypotension is associated with a 36% increase
      in the risk of overall mortality. A systematic review of the literature suggests
      that orthostatic hypotension is also associated with a higher risk for
      cardiovascular events. Insufficient data are available to enable a precise
      assessment of the association of orthostatic hypotension with strokes and falls.

PMID- 24879491
TI  - Resting heart rate and risk of hypertension: results of the Kailuan cohort study.
AB  - OBJECTIVE: Resting heart rate (RHR) is a predictive risk factor of the
      development of cardiovascular diseases, but its association with arterial
      hypertension has remained unclear. This study investigated the relationship
      between RHR and new-onset hypertension (NOH) in an Asian population. METHODS: The
      Kailuan study is a prospective longitudinal cohort study on cardiovascular risk
      factors and cardiovascular or cerebrovascular events. Hazard ratios with 95%
      confidence intervals (CIs) were calculated using Cox regression modelling.
      RESULTS: Out of 101 510 individuals originally included into the Kailuan study,
      31 507 participants (mean age: 46.3 +/- 11.5 years) were selected with no
      previous arterial hypertension or cardiac arrhythmias. After a mean follow-up
      period of 3.5 +/- 0.9 years, 12 565 (39.88%) individuals developed arterial
      hypertension. Incidence of hypertension was 104.4, 109.7, 114.2 and 124.6 per
      1000 person-years for each RHR quartile. In multivariate analysis with adjustment
      for blood pressure, blood lipids, diabetes mellitus and other parameters, hazard
      ratios for NOH increased significantly (P < 0.0001) with increasing RHR quartile.
      Increase in RHR by 10 beats/minute was associated with an 8% increase in NOH.
      Individuals in the highest RHR quartile as compared with participants in the
      lowest quartile demonstrated a 16% greater risk of developing NOH [hazard ratio
      1.16; 95% confidence interval (CI) 1.11-1.23]. There were no significant
      interactions between RHR and prehypertension, diabetes mellitus, age and BMI in
      terms of NOH risk, respectively. CONCLUSION: Independently of other baseline
      parameters such as blood pressure, blood lipids and diabetes mellitus, elevated
      RHR significantly increases the risk of incident hypertension. Measuring RHR is
      helpful in predicting the risk of eventual arterial hypertension.

PMID- 24879492
TI  - A randomized controlled study of CPAP effect on plasma aldosterone concentration
      in patients with resistant hypertension and obstructive sleep apnea.
AB  - OBJECTIVE: The high prevalence of obstructive sleep apnea in patients with
      resistant hypertension could be mediated by an activation of the renin
      angiotensin-aldosterone system. This study assessed the impact of continuous
      positive airway pressure (CPAP) treatment on plasma aldosterone concentration
      (PAC). METHODS: One hundred and twenty-four patients with resistant hypertension
      were assessed, and those who fulfilled inclusion criteria (n = 116) underwent
      full night polysomnography, 24-h ambulatory blood pressure monitoring, and PAC
      measurement. Patients with an apnea-hypopnea index above 15 (n = 102) were
      randomized to CPAP (n = 50) or to conventional treatment (n = 52) for 3 months.
      RESULTS: Seventy-eight patients completed the follow-up (36 CPAP, 42 conventional
      treatment); 58 had true resistant hypertension (74.3%), whereas 20 had white-coat
      resistant hypertension (25.6%). Most patients were men (70.7%), age 58.3 +/- 9.4
      years, and the mean apnea-hypopnea index was 50.1 +/- 21.6. In patients with true
      resistant hypertension, CPAP achieved a significant decrease in most 24-h BP
      measurements and a nonsignificant decrease in PAC (25 +/- 8.7 vs. 22.7 +/- 9
      ng/dl; P < 0.182). In patients with white-coat resistant hypertension, CPAP
      achieved a significant decrease in PAC (26.1 +/- 11.2 vs. 18.9 +/- 10.1 ng/dl; P
      < 0.041) and in night-time DBP. After adjustment, a weak but significant
      association was found between cumulative time spent with SaO2 below 90% (CT90%)
      and baseline PAC (P < 0.047, R 0.019), and between changes in PAC and changes in
      office DBP (P < 0.020, R 0.083) CONCLUSIONS:: Night-time hypoxemia and changes in
      DBP showed an association with baseline and changes in PAC, respectively. CPAP
      achieved a significant reduction in PAC only in patients with white-coat
      resistant hypertension, although the CPAP effect on BP was highest in patients
      with true resistant hypertension.

PMID- 24879493
TI  - Cardiovascular consequences of a polygenetic component of blood pressure in an
      urban-based longitudinal study: the Malmo diet and cancer.
AB  - BACKGROUND: A recently published genome wide association study identified 29
      single nucleotide polymorphisms (SNPs) influencing blood pressure (BP). Case
      control studies suggest that a genetic risk score (GRS) based on these 29 SNPs
      affect the risk of cardiovascular disease (CVD), but its role for CVD at
      population level is unknown. Here, we prospectively evaluate the impact of this
      polygenetic BP component on CVD morbidity and mortality in a large urban-based
      middle-aged population. METHOD: The 29 previously BP associated SNPs were
      genotyped in the Swedish Malmo Diet and Cancer Study; (n = 27,003 with at least
      24 valid SNPs). The number of BP elevating alleles of each SNPs, weighted by
      their effect size in the discovery studies, was summed into a BP-GRS. RESULTS:
      Using regression models, we found significant associations of the BP-GRS, cross
      sectionally, with BP and hypertension prevalence, prospectively, with incident
      cardiovascular morbidity and mortality during 14.2 +/- 3.2 years of follow-up.
      After adjustment for traditional cardiovascular risk factors (TRF), including
      hypertension, the BP-GRS remained significantly associated only with CVDs [in
      terms of strokes and coronary artery disease; hazard ratio 1.15; 95% confidence
      interval (CI) 1.06-1.24 comparing the third vs. first tertile; P = 0.003].
      Calibration, discrimination and reclassification analyses did not show a
      meaningful increment in prediction using the BP-GRS in addition to the model
      encompassing only the TRF. CONCLUSION: The polygenetic component of BP influences
      risk of cardiovascular morbidity and mortality. However, the effect size is small
      and unlikely to be useful for prediction at the population level.

PMID- 24879494
TI  - Effect of vitamin D supplementation on orthostatic hypotension: data from the
      vitamin D in isolated systolic hypertension randomized controlled trial.
AB  - OBJECTIVE: Orthostatic hypotension commonly accompanies supine hypertension, and
      is associated with low 25-hydroxyvitamin D levels. We tested whether high-dose
      intermittent oral vitamin D therapy could ameliorate orthostatic hypotension in
      older patients with isolated systolic hypertension. METHODS: We conducted a
      subgroup analysis of data from a parallel-group, double-blind, randomized,
      placebo-controlled trial. Patients aged over 70 years with supine office SBP
      above 140 mmHg and DBP below 90 mmHg received 100 000 units oral vitamin D3 or
      matching placebo every 3 months for 1 year. Office supine and standing blood
      pressure were measured at baseline, and 3, 6, 9 and 12 months, along with
      arterial stiffness and flow-mediated dilatation of the brachial artery. RESULTS:
      Of 159 patients randomized to the main trial, 75 patients with orthostatic
      hypotension at baseline were included in this analysis. The mean age was 78 (SD
      5) years, baseline blood pressure was 162/76 mmHg and the mean baseline
      orthostatic fall in blood pressure on standing was 32/5 mmHg. After adjustment
      for baseline age, 25-hydroxyvitamin D, SBP and orthostatic fall, the fall in SBP
      was less in the vitamin D group at 3 months [treatment effect 6 mmHg, 95%
      confidence interval (CI) 0 to 12], but repeated-measures analysis showed no
      significant treatment effect (3 mmHg for systolic fall, 95% CI -1 to 8; 1 mmHg
      for diastolic fall, 95% CI -1 to 3). CONCLUSION: Twelve months of intermittent,
      high-dose oral vitamin D3 did not significantly improve orthostatic hypotension
      in older patients with isolated systolic hypertension.

PMID- 24879495
TI  - Acute subjective effects after smoking joints containing up to 69 mg Delta9
      tetrahydrocannabinol in recreational users: a randomized, crossover clinical
      trial.
AB  - RATIONALE: An increase in the potency of the cannabis cigarettes has been
      observed over the past three decades. OBJECTIVES: In this study, we aimed to
      establish the impact of Delta9-tetrahydrocannabinol (THC) on the rating of
      subjective effects (intensity and duration of the effects), up to 23 % THC
      potency (69 mg THC) among recreational users. METHODS: Recreational users (N =
      24) smoked cannabis cigarettes with four doses of THC (placebo 29, 49 and 69 mg
      of THC) on four separate test days in a randomized, double-blind, placebo
      controlled, crossover study. The participants filled in three different
      questionnaires measuring subjective effects during the exposure up to 8 h post
      smoking. The 'high' feeling, heart rate, blood pressure and THC serum
      concentrations were also regularly recorded during these 8 h. RESULTS: THC
      significantly increased the high feeling, dizziness, dry-mouthed feeling,
      palpitations, impaired memory and concentration, and 'down', 'sedated' and
      'anxious' feelings. In addition, THC significantly decreased alertness,
      contentment and calmness. A cubic relationship was observed between 'feeling the
      drug' and 'wanting more'. The THC-induced decrease in 'feeling stimulated' and
      increase in anxiety lasted up to 8 h post-smoking. Sedation at 8 h post-smoking
      was increased by a factor of 5.7 with the highest THC dose, compared to the
      placebo. CONCLUSIONS: This study shows a strong effect of cannabis containing
      high percentages of THC on the rating of subjective effects. Regular users and
      forensic toxicologists should be aware that the THC-induced increase in 'feeling
      sedated' continues longer with a 69 mg THC dose than with a 29 mg THC dose.

PMID- 24879496
TI  - Selective blockade of N-methyl-D-aspartate channels in combination with dopamine
      receptor antagonism induces loss of the righting reflex in mice, but not
      immobility.
AB  - RATIONALE: The selective N-methyl-D-aspartate (NMDA) channel blocker MK-801 is
      known to induce no loss of the righting reflex (LORR) and to stimulate
      catecholaminergic (CAergic) neurons in rodents, playing a crucial role in
      arousal. OBJECTIVES: We examined whether MK-801 in combination with CA receptor
      ligands, which inhibit CAergic neuronal activities, could induce anesthesia
      including LORR. METHODS: All drugs were administered systemically to mice. To
      assess anesthesia, three different behaviors were used: loss of nociceptive
      response (analgesia in the free-moving state without LORR), LORR, and loss of
      movement in response to noxious stimulation (immobility under LORR). RESULTS: A
      very large dose of MK-801 (50 mg/kg) induced neither analgesia nor LORR. In
      contrast, MK-801 in combination with a small dose of the dopamine (DA) receptor
      antagonist haloperidol (0.2 mg/kg) dose-dependently produced LORR with a 50 %
      effective dose (ED50) of 1.6 (0.9-3.0; 95 % confidence limit) mg/kg, but not
      immobility. The alpha2-adrenoceptor agonist dexmedetomidine induced not only
      analgesia, but also immobility in animals treated with MK-801 (5 mg/kg) plus
      haloperidol (0.2 mg/kg), which then lost their righting reflex. The ED50 value of
      0.26 (0.10-0.66) mg/kg (various doses of dexmedetomidine plus a fixed dose of MK
      801 and haloperidol) for immobility was approximately three-fold larger than that
      of 0.09 (0.03-0.23) mg/kg (dexmedetomidine plus vehicle saline) for analgesia.
      This may occur, as LORR induced by MK-801 plus haloperidol inhibits the pain
      suppression system. The other ligands had little or no effect. CONCLUSIONS: The
      DAergic stimulant actions of MK-801 may mask its LORR effects by NMDA channel
      blockade.

PMID- 24879498
TI  - We stand upon the shoulders of giants!

PMID- 24879497
TI  - The effect of chronic phenytoin administration on single prolonged stress induced
      extinction retention deficits and glucocorticoid upregulation in the rat medial
      prefrontal cortex.
AB  - RATIONALE: Post-traumatic stress disorder (PTSD) is a chronic, debilitating
      disorder. Only two pharmacological agents are approved for PTSD treatment, and
      they often do not address the full range of symptoms nor are they equally
      effective in all cases. Animal models of PTSD are critical for understanding the
      neurobiology involved and for identification of novel therapeutic targets. Using
      the rodent PTSD model, single prolonged stress (SPS), we have implicated aberrant
      excitatory neural transmission and glucocorticoid receptor (GR) upregulation in
      the medial prefrontal cortex (mPFC) and hippocampus (HPC) in fear memory
      abnormalities associated with PTSD. OBJECTIVE: The objective of this study is to
      examine the potential protective effect of antiepileptic phenytoin (PHE)
      administration on SPS-induced extinction retention deficits and GR expression.
      METHODS: Forty-eight SPS-treated male Sprague Dawley rats or controls were
      administered PHE (40, 20 mg/kg, vehicle) for 7 days following SPS stressors;
      then, fear conditioning, extinction, and extinction retention were tested.
      RESULTS: Fear conditioning and extinction were unaffected by SPS or PHE, but SPS
      impaired extinction retention, and both doses of PHE rescued this impairment.
      Similarly, SPS increased GR expression in the mPFC and dorsal HPC, and PHE
      prevented SPS-induced GR upregulation in the mPFC. CONCLUSIONS: These data
      demonstrate that PHE administration can prevent the development of extinction
      retention deficits and upregulation of GR. PHE exerts inhibitory effects on
      voltage-gated sodium channels and decreases excitatory neural transmission via
      glutamate antagonism. If glutamate hyperactivity in the days following SPS
      contributes to SPS-induced deficits, then these data may suggest that the
      glutamatergic system constitutes a target for secondary prevention.

PMID- 24879500
TI  - Importance of cannulated prolactin test in the definition of hyperprolactinaemia.
AB  - PURPOSE: Recent guidelines suggest that a single prolactin measurement is
      adequate to confirm hyperprolactinaemia. This may lead to unnecessary
      investigation of artefactual hyperprolactinaemia. Prolactin measurement drawn
      from an indwelling cannula after rest removes stress as a confounding variable.
      The objective was to determine the frequency of true hyperprolactinaemia amongst
      patients referred following a single prolactin measurement. METHODS: A cannulated
      study was considered if prolactin on referral ('Referral Prolactin') was <5,500
      mU/L (260 ng/mL) but >410 mU/L (19 ng/mL) in males or >510 mU/L (24 ng/mL) in
      females, irrespective of clinical context. Case-notes of 267 patients undergoing
      cannulated prolactin measurement over a 10-year period (2000-2010) were reviewed.
      Pre-existing pituitary disease, dopamine antagonist use, and macroprolactinaemia
      were excluded. Morning ante-cubital vein cannulation was followed immediately by
      withdrawal of 'Repeat Prolactin' sample. After 120-min bed-rest, 'Resting
      Prolactin' was withdrawn through the cannula. RESULTS: 235 patients were included
      for analysis. 64 (27%) were within normal range; following Repeat Prolactin in 41
      (17%) and Resting Prolactin in 23 (9%) cases. Referral Prolactin was higher in
      patients with true hyperprolactinaemia, 1,637 +/- 100 mU/L (77.2 +/- 4.7 ng/mL)
      than with artefactual hyperprolactinaemia, 1,122 +/- 68 mU/L (52.9 +/- 3.2 ng/mL;
      P < 0.001) but there was substantial overlap. 21 out of 171 cases (12%) with true
      hyperprolactinaemia had a macroadenoma. Presenting symptoms did not predict true
      hyperprolactinaemia. Referral Prolactin of 2,000 mU/L (94 ng/mL) had 97%
      specificity to identify true hyperprolactinaemia. CONCLUSIONS: Reliance on a
      single, non-rested prolactin value may lead to over-diagnosis of
      hyperprolactinaemia. A resting sample should be considered with random values
      <2,000 mU/L (94 ng/mL).

PMID- 24879499
TI  - Insulin resistance, metabolic syndrome and chronic low grade inflammation in
      Sheehan's syndrome on standard replacement therapy: a case control study.
AB  - BACKGROUND: Increased clustering of metabolic risk factors has been demonstrated
      in patients with hypopituitarism on standard replacement therapy. This usually
      has been attributed to persistent growth hormone deficiency, though contribution
      from underlying etiology of hypopituitarism cannot be underestimated. We,
      therefore, studied conventional metabolic risk factors and pro inflammatory
      markers in a cohort of hypopituitary patients in whom the etiology was Sheehan's
      syndrome. MATERIAL & METHODS: We studied 30 GH naive patients with Sheehan's
      syndrome (SS) on standard replacement therapy and compared with healthy age, BMI
      and parity matched controls. All subjects were normotensive, non-diabetic, non
      smokers and none had history of any acute or chronic illness. We recorded height,
      weight, BMI, waist circumference and waist hip ratio, besides measuring
      biochemical parameters like lipid profile, fasting plasma glucose and insulin,
      sVCAM-1, ICAM-1 and hsCRP. RESULTS: Metabolic syndrome and impaired glucose
      tolerance were more common with SS patients. Similarly total cholesterol (mean +/
      SD, 5.21 +/- 0.98 vs 4.57 +/- 0.88, P = 0.00), LDL-cholesterol (3.15 +/- 0.90 vs
      2.67 +/- 0.75, P = 0.02), triglycerides (2.14 +/- 1.00 vs 1.43 +/- 0.45, P =
      0.00) and pro-inflammatory markers i.e. hsCRP (3.95 +/- 2.58 vs 1.45 +/- 2.77, P
      = 0.00) were significantly higher in patients with SS. hsCRP positively
      correlated with fasting insulin (r = 0.40, P = 0.02), HOMA-IR (r = 0.38, P =
      0.03) and negatively with HDL (r = - 0.33, P = 0.05). CONCLUSIONS: GH naive SS
      patients on standard replacement therapy have increased clustering of metabolic
      and pro-inflammatory risk factors.

PMID- 24879501
TI  - Novel operative anoscope for Ferguson hemorrhoidectomy: a feasibility study and
      comparative cohort analysis.
AB  - BACKGROUND: Operative hemorrhoidectomy can result in pain and altered continence
      from excessive excision of anoderm or surrounding tissue. We assessed a novel low
      profile slotted anoscope to determine if the device would promote safe
      dissection, lessen trauma, and reduce operative times for hemorrhoidectomy.
      METHODS: Patients requiring hemorrhoidectomy (June 2008 - January 2010) underwent
      a prospective phase-2 trial evaluating a new operating anoscope (CAD, Ethicon
      Endosurgery, Cincinnati, OH). Demographics and perioperative end points including
      bleeding, pain, fecal incontinence, stenosis, and symptom recurrence were
      analyzed at 4 weeks, 3 months, 6 months, and 1 year postoperatively. We compared
      these to patients undergoing hemorrhoidectomy (February 2010 - November 2012)
      with a traditional Hill-Ferguson anoscope (THF). RESULTS: 40 patients (CAD, 20 vs
      THF, 20) were included. Presenting symptoms were similar, whereas mean duration
      of symptoms was longer for CAD (41.2 +/- 8.4 vs 27 +/- 9.5 months; P < .05).
      Estimated blood loss was lower for CAD [8.3 mL (range = 2-40 mL) vs 11.3 mL THF
      (range = 5-35 mL; P = .87)]. Mean operative times were lower for the CAD than the
      THF group (15.6 +/- 3.4 vs 26.1 +/- 4.1 minutes; P < .05). Visual analog pain
      scores were non-significantly increased in the THF group at 4 weeks (P = .23). At
      3 months, 6 months, and 1 year, there was no difference in continence.
      CONCLUSION: The CAD anoscope reduced operative times for modified Ferguson
      (closed) hemorrhoidectomy when compared with traditional retractors. There was no
      difference in incontinence or pain between groups.

PMID- 24879502
TI  - Female stress urinary incontinence: clinical efficacy and satisfaction after
      transobturator adjustable tape sling. An observational longitudinal cohort study.
AB  - We performed an observational longitudinal cohort study on patients affected by
      stress urinary incontinence (SUI) and surgically treated with a transobturator
      adjustable tape sling (TOA) in order to evaluate this surgical procedure in terms
      of efficacy, safety, quality of life (QoL) improvement, and patient satisfaction.
      For all patients, we recorded: general features, preoperative SUI risk factors,
      obstetrics history, preoperative urodynamic tests, intraoperative/postoperative
      complications, number of postoperative sling regulations, postmicturition
      residue, and hospital stay. All patients were asked to complete the validated
      short version of the Urogenital Distress Inventory (UDI-6) questionnaire 18
      months after discharge to evaluate the efficacy of the TOA system. We added 2
      adjunctive items to the UDI-6 in order to evaluate patient satisfaction and QoL.
      All 77 surgical procedures were performed under locoregional anesthesia without
      complications. Postoperative TOA regulations were performed in 46.8% of patients
      immediately after the procedure and in 14.3% during hospitalization. Before
      discharge, postmicturition residue was negative in 67 cases and less than 50 cc
      in 10 cases. Mean hospital stay was 2.18 days. From the questionnaire evaluation,
      we found that after the procedure, 90.9% of patients showed a complete regression
      of urinary symptoms, 1.3% obtained considerable relief from preoperative
      symptoms, and 6.6% reported poor or absent symptom improvements; 75.3% of
      patients were totally satisfied and 5.2% totally disappointed. The possibility of
      modulating postoperative sling tension and reusing the surgical materials in
      association with short hospitalization as well as high patient satisfaction
      render TOA a safe, effective, and low-cost technique for the treatment of female
      SUI. 

PMID- 24879503
TI  - A novel technique to predict pulmonary capillary wedge pressure utilizing central
      venous pressure and tissue Doppler tricuspid/mitral annular velocities.
AB  - Assessing left ventricular (LV) filling pressure (pulmonary capillary wedge
      pressure, PCWP) is an important aspect in the care of patients with heart failure
      (HF). Physicians rely on right ventricular (RV) filling pressures such as central
      venous pressure (CVP) to predict PCWP, assuming concordance between CVP and PCWP.
      However, the use of this method is limited because discordance between CVP and
      PCWP is observed. We hypothesized that PCWP can be reliably predicted by CVP
      corrected by the relationship between RV and LV function, provided by the ratio
      of tissue Doppler peak systolic velocity of tricuspid annulus (S(T)) to that of
      mitral annulus (S(M)) (corrected CVP:CVP.S(T)/S(M)). In 16 anesthetized closed
      chest dogs, S T and S M were measured by transthoracic tissue Doppler
      echocardiography. PCWP was varied over a wide range (1.8-40.0 mmHg) under normal
      condition and various types of acute and chronic HF. A significantly stronger
      linear correlation was observed between CVP.S(T)/S(M) and PCWP (R2 = 0.78) than
      between CVP and PCWP (R2 = 0.22) (P < 0.01). Receiver-operating characteristic
      (ROC) analysis indicated that CVP.S(T)/S(M) >10.5 mmHg predicted PCWP >18 mmHg
      with 85% sensitivity and 88% specificity. Area under ROC curve for CVP.S T/S M to
      predict PCWP >18 mmHg was 0.93, which was significantly larger than that for CVP
      (0.66) (P < 0.01). Peripheral venous pressure (PVP) corrected by S T/S M
      (PVP.S(T)/S(M) also predicted PCWP reasonably well, suggesting that PVP.S(T)/S
      (M) may be a minimally invasive alternative to CVP.S(T)/S(M) In conclusion, our
      technique is potentially useful for the reliable prediction of PCWP in HF
      patients.

PMID- 24879504
TI  - Effect of purified eicosapentaenoic acid on red cell distribution width in
      patients with ischemic heart disease.
AB  - A recent study showed eicosapentaenoic acid (EPA) is a promising treatment for
      prevention of coronary events in hypercholesterolemic patients. Meanwhile, a high
      red blood cell distribution width (RDW) is a known risk factor for cardiovascular
      events. However, few studies have addressed the association between EPA levels
      and RDW. We examined whether EPA administration reduced the levels of RDW in
      patients with ischemic heart disease (IHD). We retrospectively analyzed the data
      of 66 EPA-treated IHD patients, and these EPA-treated patients were compared with
      control IHD patients. The median follow-up period was 189 days in EPA-treated
      patients. All patients were not associated with anemia. In the follow-up period,
      the ratio of EPA levels to arachidonic acid levels (EPA/AA) was significantly
      increased. A significant decrease was observed in RDW at follow-up [DeltaRDW (%);
      EPA vs. control = -0.34 +/- 0.84 (SD) vs. 0.08 +/- 0.86, P < 0.01]. These RDW
      changes were more marked in diabetic patients with high serum levels of high
      sensitive C-reactive protein (hs-CRP) [DeltaRDW (%); EPA vs. control = -0.53 +/-
      0.69 vs. 0.56 +/- 0.85, P < 0.01]. There was no correlation between the amount of
      change in EPA/AA and RDW (R = 0.037, P = 0.32), but a significant negative
      correlation was observed in diabetic patients with high hs-CRP levels (N = 14, R
      = -0.506, P = 0.046). In conclusion, EPA has the potential to reduce RDW in IHD
      patients. This effect was intensified especially among diabetic patients with
      high hs-CRP levels. IHD patients with high RDW levels may be suitable for
      treatment with purified EPA. 

PMID- 24879506
TI  - Novel 3-arylethynyl-substituted thieno[3,4-b]pyrazine derivatives as human
      transglutaminase 2 inhibitors.
AB  - In the process of optimization, we developed a novel core skeleton of thieno[3,4
      b]pyrazine via GK-13. The derivatives synthesized were shown to inhibit TGase 2
      activity in cancer cells. Some of the hit compounds such as the arylethynyl group
      coupled thieno[3,4-b]pyrazine derivatives were shown to exhibit promising
      activity for use as potential therapeutic small-molecules in renal cancer by
      inhibiting TGase 2 activity.

PMID- 24879505
TI  - A P2X7 receptor antagonist attenuates experimental autoimmune myocarditis via
      suppressed myocardial CD4+ T and macrophage infiltration and NADPH oxidase 2/4
      expression in mice.
AB  - Myocarditis is a clinically serious disease; however, no effective treatment has
      been elucidated. The P2X7 receptor is related to the pathophysiology of
      inflammation in many cardiovascular diseases. The P2X7 receptor antagonist is
      promising as an immunosuppressive treatment; however, its role in myocarditis is
      still to be established. To clarify the role of the P2X7 receptor, we used a
      murine experimental autoimmune myocarditis (EAM) model. Mice were immunized on
      day 0 and 7 with synthetic cardiac myosin peptide to establish EAM. The mice with
      induced EAM were treated with A740003, the P2X7 receptor antagonist (n = 10), or
      not treated (n = 11); hearts were harvested on day 21. The P2X7 receptor
      antagonist improved myocardial contraction of the EAM hearts via suppressed
      infiltration of CD4+ T cells and macrophages. Similarly, mRNA expression of
      interleukin 1 beta, the P2X7 receptor and NADPH oxidase 2/4 was lower in the
      heart of the P2X7 receptor antagonist-treated group compared to the non-treat
      group. The P2X7 receptor antagonist suppressed EAM development; thus, this
      inhibition is promising for treating clinical myocarditis.

PMID- 24879508
TI  - Optimizing the magnetization-prepared rapid gradient-echo (MP-RAGE) sequence.
AB  - The three-dimension (3D) magnetization-prepared rapid gradient-echo (MP-RAGE)
      sequence is one of the most popular sequences for structural brain imaging in
      clinical and research settings. The sequence captures high tissue contrast and
      provides high spatial resolution with whole brain coverage in a short scan time.
      In this paper, we first computed the optimal k-space sampling by optimizing the
      contrast of simulated images acquired with the MP-RAGE sequence at 3.0 Tesla
      using computer simulations. Because the software of our scanner has only limited
      settings for k-space sampling, we then determined the optimal k-space sampling
      for settings that can be realized on our scanner. Subsequently we optimized
      several major imaging parameters to maximize normal brain tissue contrasts under
      the optimal k-space sampling. The optimal parameters are flip angle of 12 degrees
      , effective inversion time within 900 to 1100 ms, and delay time of 0 ms. In vivo
      experiments showed that the quality of images acquired with our optimal protocol
      was significantly higher than that of images obtained using recommended protocols
      in prior publications. The optimization of k-spacing sampling and imaging
      parameters significantly improved the quality and detection sensitivity of brain
      images acquired with MP-RAGE. 

PMID- 24879509
TI  - Structural, electronic and energetic properties of giant icosahedral fullerenes
      up to C6000: insights from an ab initio hybrid DFT study.
AB  - The properties of the (n,n) icosahedral family of carbon fullerenes up to n = 10
      (6000 atoms) have been investigated through ab initio quantum-mechanical
      simulation by using a Gaussian type basis set of double zeta quality with
      polarization functions (84,000 atomic orbitals for the largest case), the hybrid
      B3LYP functional and the CRYSTAL14 code featuring generalization of symmetry
      treatment. The geometry of giant fullerenes shows hybrid features, between a
      polyhedron and a sphere; as n increases, it approaches the former. Hexagon rings
      at face centres take a planar, graphene-like configuration; the 12 pentagon rings
      at vertices impose, however, a severe structural constraint to which hexagon
      rings at the edges must adapt smoothly, adopting a bent (rather than sharp)
      transversal profile and an inward longitudinal curvature. The HOMO and LUMO
      electronic levels, as well as the band gap, are well described using power laws.
      The gap is predicted to become zero for n >= 34 (69,360 atoms). The atomic excess
      energy with respect to the ideal graphene sheet goes to zero following the
      log(Nat)/Nat law, which is well described through the continuum elastic theory
      applied to graphene; the limits for the adopted model are briefly outlined.
      Compared to larger fullerenes of the series, C60 shows unique features with
      respect to all the considered properties; C240 presents minor structural and
      energetic peculiarities, too.

PMID- 24879507
TI  - Novel assessment tools for osteoporosis diagnosis and treatment.
AB  - This review describes new technologies for the diagnosis and treatment, including
      fracture risk prediction, of postmenopausal osteoporosis. Four promising
      technologies and their potential for clinical translation and basic science
      studies are discussed. These include reference point indentation (RPI), Fourier
      transform infrared spectroscopy (FTIR), Raman spectroscopy, and magnetic
      resonance imaging (MRI). While each modality exploits different physical
      principles, the commonality is that none of them require use of ionizing
      radiation. To provide context for the new developments, brief summaries are
      provided for the current state of biomarker assays, fracture risk assessment
      (FRAX), and other fracture risk prediction algorithms and quantitative ultrasound
      (QUS) measurements.

PMID- 24879510
TI  - Zearalenone degradation by two Pseudomonas strains from soil.
AB  - This study describes the screening of soil bacteria for their capability to
      degrade zearalenone (ZEN), employing an enrichment technique in which ZEN is used
      as the sole carbon source. Two isolates that were able to degrade ZEN belonged to
      the genus Pseudomonas according to biochemical characterization and 16S rRNA gene
      sequence and were named as Pseudomonas alcaliphila TH-C1 and Pseudomonas
      plecoglossicida TH-L1, respectively. The results showed that the degradation
      rates of P. alcaliphila TH-C1 and P. plecoglossicida TH-L1 for ZEN (2 MUg/ml)
      were 68 +/- 0.85 % and 57 +/- 0.73%, when incubated for 72 h at 30  degrees C in
      a rotary shaker (160 rpm) and detected by high-performance liquid chromatograms
      (HPLC). These results suggest that the two Pseudomonas strains are new bacterial
      resource for degrading ZEN and can provide a new approach for the detoxification
      of ZEN.

PMID- 24879511
TI  - Panniculitis in patients treated with BRAF inhibitors: a case series.
AB  - Panniculitis is a rare complication of BRAF inhibitor therapy that is used to
      treat patients with BRAF-mutated metastatic melanoma. We present a
      clinicopathologic review of 9 patients who developed panniculitis while on BRAF
      inhibitor therapy. In 13% of patients on vemurafenib, 3% of patients on
      dabrafenib and 10% on combination of dabrafenib + trametinib, tender erythematous
      nodular lesions of panniculitis appeared on legs, arms and trunk. Histological
      evaluation of 8 biopsies from 7 patients showed predominantly neutrophilic
      infiltrate in 4, lymphocytic in 1, and mixed in 3. Lesions with neutrophilic
      infiltrate appeared in earlier stages of treatment than those with mixed or
      lymphocytic infiltrate. All biopsies showed lobular involvement and 5 also had a
      septal component. In addition, 1 biopsy had lichenoid inflammation in the
      epidermis and the other had evidence of vasculitis. Most patients responded to
      conservative medical management without the need to reduce or to stop BRAF
      inhibitor therapy. Panniculitis seems to be a rare class effect of BRAF
      inhibitors that is predominantly lobular and neutrophilic, although other
      patterns can be seen.

PMID- 24879512
TI  - Relapsing painful multiple ulcerative skin eruptions: challenge.

PMID- 24879515
TI  - Leprosy: a diagnostic trap for dermatopathologists even in endemic areas.

PMID- 24879513
TI  - A rare case of melanoma with Touton-like giant cells: a potential diagnostic
      pitfall.
AB  - Although approximately 876,000 individuals in the United States currently have a
      diagnosis of melanoma, the Touton-like giant cell variant has been described only
      twice in the literature to date. In our case, a 70-year-old man with a history of
      sclerosing carcinoma on the scalp presented for evaluation of a new nodularity at
      the site of his previous surgery. On examination, a new complex pigmented lesion
      on the posterolateral scalp, adjacent to the recurrent sclerosing carcinoma, was
      noted. Biopsy of the pigmented lesion revealed an invasive melanoma with a
      Breslow depth of at least 2.78 mm. Microscopic sections showed a predominantly
      dermal-based tumor composed of sheets and nests of enlarged epithelioid cells.
      These cells contained oval-to-reniform nuclei with prominent nucleoli and an
      abundant amount of eosinophilic to vacuolated cytoplasm. Interestingly, numerous
      multinucleated melanocytes, some with a "Touton" appearance, were scattered
      throughout the lesion. The lesional cells demonstrated positivity to Mart-1 and
      HMB-45. Fortunately, the patient's sentinel lymph node biopsy was negative for
      micrometastases, and a subsequent Position Emission Tomography (PET) scan was
      unremarkable. Documentation of individual cases of this rare histologic variant
      of melanoma is necessary given the ability of this lesion to mimic benign
      histiocytic proliferations at scanning magnification.

PMID- 24879516
TI  - Viola mandshurica ethanolic extract prevents high-fat-diet-induced obesity in
      mice by activating AMP-activated protein kinase.
AB  - Viola mandshurica W. Becker has been used as an expectorant, diuretic, and anti
      inflammatory agent. We evaluated the effects of V. mandshurica ethanol extract
      (VME) on high-fat-diet (HFD)-induced obesity in mice. HPLC analysis showed that
      the VME contained 11.95 +/- 0.37 mg/g esculetin and 0.13 +/- 0.01 mg/g
      scopoletin. Orally administered VME decreased the body weight, adipose tissue
      mass, adipocyte size, and triglyceride and leptin serum concentrations. In
      contrast, VME increased serum adiponectin concentrations and adiponectin
      expression levels in epididymal adipose tissues. VME also significantly reversed
      the HFD-induced elevation of the mRNA and protein levels of lipogenic genes such
      as peroxisome proliferator-activated receptor gamma, sterol regulatory element
      binding protein-1c, fatty-acid synthase, and adipocyte protein 2. Moreover, VME
      reversed the HFD-induced inhibition of AMP-activated protein kinase (AMPK) and
      acetyl-coA carboxylase phosphorylation in epididymal adipose tissues.
      Furthermore, treatment of VME and esculetin in 3T3-L1 cells inhibited adipocyte
      differentiation and fat accumulation. These results suggest that VME exerts anti
      obesity effects in HFD-induced obese mice by activating AMPK and suppressing
      PPARgamma expression in adipose tissues.

PMID- 24879517
TI  - Fragment ion diagnostic strategies for the comprehensive identification of
      chemical profile of Gui-Zhi-Tang by integrating high-resolution MS, multiple
      stage MS and UV information.
AB  - Gui-Zhi-Tang was considered to be the most famous formula in Shang-Han-Lun,
      treating 32 symptoms of disease after adding up or cutting down crude drugs. The
      chemical constituents in Gui-Zhi-Tang were comprehensively studied by rapid
      resolution liquid chromatography quadrupole time-of-flight mass spectrometry
      (RRLC-Q-TOF-MS) combined with rapid resolution liquid chromatography - diode
      array detector - ion trap mass spectrometry (RRLC-DAD-IT-MS) in this work, and a
      total number of 187 compounds were detected. Systematic diagnostic ion filtering
      strategies were recommended for flavonoids and oleanane-type triterpenoids,
      respectively. On the basis of the summarized strategies, compounds in
      Glycyrrhizae could be easily classified into flavones, isoflavones, flavanones or
      chalcones with special structures, and triterpene saponins with different sugar
      moieties. Consequently, among 187 compounds, 144 ones were confirmed or assumed
      tentatively. In addition, nine potential novel compounds were reported for the
      first time. This approach provided a rapid method for characterizing the
      constituents in Gui-Zhi-Tang, and would be also helpful in other TCM formulae
      analysis. 

PMID- 24879518
TI  - Isolation and characterization of a beta-glucuronide of hydroxylated SARM S1
      produced using a combination of biotransformation and chemical oxidation.
AB  - In this study, using mass spectrometry and nuclear magnetic resonance (NMR)
      spectroscopy, it has been confirmed that biotransformation with the fungus
      Cunninghamella elegans combined with chemical oxidation with the free radical
      tetramethylpiperidinyl-1-oxy (TEMPO) can produce drug glucuronides of beta
      configuration. Glucuronic acid conjugates are a common type of metabolites formed
      by the human body. The detection of such conjugates in doping control and other
      kinds of forensic analysis would be beneficial owing to a decrease in analysis
      time as hydrolysis can be omitted. However the commercial availability of
      reference standards for drug glucuronides is poor. The selective androgen
      receptor modulator (SARM) SARM S1 was incubated with the fungus C. elegans. The
      sample was treated with the free radical TEMPO oxidizing agent and was thereafter
      purified by SPE. A glucuronic acid conjugate was isolated using a fraction
      collector connected to an ultra high performance liquid chromatographic (UHPLC)
      system. The isolated compound was characterized by NMR spectroscopy and mass
      spectrometry and its structure was confirmed as a glucuronic acid beta-conjugate
      of hydroxylated SARM S1 bearing the glucuronide moiety on carbon C-10. 

PMID- 24879520
TI  - Electronic and magnetic properties of honeycomb transition metal monolayers:
      first-principles insights.
AB  - p-Electron-based monolayer materials have dominated the research of Dirac
      fermions since the first exfoliation of graphene. In the present work, the
      electronic and magnetic properties of d-electron-based Dirac systems are studied
      by combining first-principles with mean field theory and Monte Carlo approaches.
      From first-principles calculations, we demonstrate that transition-metal (TM)
      monolayers (TM = Ti, Zr, Hf, V, Nb, or Ta), d-electron-based materials, could
      also hold Dirac cones and not only p-electron-based materials as known before.
      This may shed light on the breakthrough of new nanomaterials with d-type Dirac
      points. Moreover, the carrier mobility near the Dirac points of these materials
      can be tuned regularly by isotropic strains from -5% to 5%, without breaking the
      Dirac cones. However, the Dirac points would disappear under anisotropic strains,
      indicating that a rigorous honeycomb lattice may be the main precondition for
      Dirac points in TM-monolayers. Furthermore, some TM-monolayers (TM = Ti, Zr, or
      Hf) exhibit ferromagnetic couplings simultaneously. In addition, by mean field
      theory and Monte Carlo methods, it is found that Curie temperatures of TM
      monolayers can be higher than 580 K even to 1180 K. Our findings significantly
      expand the Dirac systems. 

PMID- 24879519
TI  - Chromosome distribution of early miscarriages with present or absent embryos:
      female predominance.
AB  - PURPOSE: The objective of this study is to compare the chromosomal distribution
      of early miscarriages with or without embryonic poles. MATERIALS AND METHODS: It
      was a retrospective study of 223 women who underwent dilation and curettage (D&C)
      between 1995 and 2013 for early miscarriages. The presence or absence of a fetal
      pole was evaluated by abdominal or transvaginal ultrasound. Cytogenetic tests of
      products of conception following culture were determined in both groups. RESULTS:
      Of the 223 early miscarriages, 143 had embryos and 80 did not. The abnormality
      rate differed significantly (61.5 % vs. 46.3 %, p < 0.05), with trisomy 18, 21
      and 45X found only in miscarriages with embryos. There were no significant
      differences between groups in rates of triploidy, tetraploidy, mosaicism,
      structure and double abnormality. The female abortus rate was higher in
      miscarriages with or without embryonic poles, as well as in groups with normal
      and abnormal karyotypes. CONCLUSIONS: Chromosome distribution differs in
      miscarriages with or without embryonic poles. The ultrasound findings might offer
      different direction to determine the causes of early miscarriages. The higher
      female abortus rate may be associated with early selection.

PMID- 24879521
TI  - Synthesis, characterization and photocatalytic activity of new photocatalyst
      ZnBiSbO4 under visible light irradiation.
AB  - In this paper, ZnBiSbO4 was synthesized by a solid-state reaction method for the
      first time. The structural and photocatalytic properties of ZnBiSbO4 had been
      characterized by X-ray diffraction, scanning electron microscopy, X-ray
      photoelectron spectroscopy, Fourier-transform infrared spectroscopy, transmission
      electron microscope and UV-visible spectrometer. ZnBiSbO4 crystallized with a
      pyrochlore-type structure and a tetragonal crystal system. The band gap of
      ZnBiSbO4 was estimated to be 2.49 eV. The photocatalytic degradation of indigo
      carmine was realized under visible light irradiation with ZnBiSbO4 as a catalyst
      compared with nitrogen-doped TiO2 (N-TiO2) and CdBiYO4. The results showed that
      ZnBiSbO4 owned higher photocatalytic activity compared with N-TiO2 or CdBiYO4 for
      the photocatalytic degradation of indigo carmine under visible light irradiation.
      The reduction of the total organic carbon, the formation of inorganic products,
      SO4(2-) and NO3(-), and the evolution of CO2 revealed the continuous
      mineralization of indigo carmine during the photocatalytic process. One possible
      photocatalytic degradation pathway of indigo carmine was obtained. The
      phytotoxicity of the photocatalytic-treated indigo carmine (IC) wastewater was
      detected by examining its effect on seed germination and growth.

PMID- 24879522
TI  - A novel VHH antibody targeting the B cell-activating factor for B-cell lymphoma.
AB  - OBJECTIVE: To construct an immune alpaca phage display library, in order to
      obtain a single domain anti-BAFF (B cell-activating factor) antibody. METHODS:
      Using phage display technology, we constructed an immune alpaca phage display
      library, selected anti-BAFF single domain antibodies (sdAbs), cloned three anti
      BAFF single-domain antibody genes into expression vector pSJF2, and expressed
      them efficiently in Escherichia coli. The affinity of different anti-BAFF sdAbs
      were measured by Bio layer interferometry. The in vitro biological function of
      three sdAbs was investigated by cell counting kit-8 (CCK-8) assay and a
      competitive enzyme-linked immunosorbent assay (ELISA). RESULTS: We obtained three
      anti-BAFF single domain antibodies (anti-BAFF64, anti-BAFF52 and anti-BAFFG3),
      which were produced in high yield in Escherichia coli and inhibited tumor cell
      proliferation in vitro. CONCLUSION: The selected anti-BAFF antibodies could be
      candidates for B-cell lymphoma therapies.

PMID- 24879523
TI  - Evaluation of zosteric acid for mitigating biofilm formation of Pseudomonas
      putida isolated from a membrane bioreactor system.
AB  - This study provides data to define an efficient biocide-free strategy based on
      zosteric acid to counteract biofilm formation on the membranes of submerged
      bioreactor system plants. 16S rRNA gene phylogenetic analysis showed that
      gammaproteobacteria was the prevalent taxa on fouled membranes of an Italian
      wastewater plant. Pseudomonas was the prevalent genus among the cultivable
      membrane-fouler bacteria and Pseudomonas putida was selected as the target
      microorganism to test the efficacy of the antifoulant. Zosteric acid was not a
      source of carbon and energy for P. putida cells and, at 200 mg/L, it caused a
      reduction of bacterial coverage by 80%. Biofilm experiments confirmed the
      compound caused a significant decrease in biomass (-97%) and thickness (-50%),
      and it induced a migration activity of the peritrichous flagellated P. putida
      over the polycarbonate surface not amenable to a biofilm phenotype. The low
      octanol-water partitioning coefficient and the high water solubility suggested a
      low bioaccumulation potential and the water compartment as its main environmental
      recipient and capacitor. Preliminary ecotoxicological tests did not highlight
      direct toxicity effects toward Daphnia magna. For green algae Pseudokirchneriella
      subcapitata an effect was observed at concentrations above 100 mg/L with a
      significant growth of protozoa that may be connected to a concurrent algal growth
      inhibition. 

PMID- 24879524
TI  - Molecular biology of brain metastasis.
AB  - Metastasis to the central nervous system (CNS) remains a major cause of morbidity
      and mortality in patients with systemic cancer. As the length of survival in
      patients with systemic cancer improves, thanks to multimodality therapies,
      focusing on metastases to the CNS becomes of paramount importance. Unique
      interactions between the brain's micro-environment, blood-brain barrier, and
      tumor cells are hypothesized to promote distinct molecular features in CNS
      metastases that may require tailored therapeutic approaches. This review will
      focus on the pathophysiology, epigenetics, and immunobiology of brain metastases
      in order to understand the metastatic cascade. Cancer cells escape the primary
      tumor, intravasate into blood vessels, survive the hematogenous dissemination to
      the CNS, arrest in brain capillaries, extravasate, proliferate, and develop
      angiogenic abilities to establish metastases. Molecular biology, genetics, and
      epigenetics are rapidly expanding, enabling us to advance our knowledge of the
      underlying mechanisms involved. Research approaches using cell lines that
      preferentially metastasize in vivo to the brain and in vitro tissue-based studies
      unfold new molecular leads into the disease. It is important to identify and
      understand the molecular pathways of the metastatic cascade in order to target
      the investigation and development of more effective therapies and research
      directions. 

PMID- 24879525
TI  - Identification of differentially expressed miRNAs between white and black hair
      follicles by RNA-sequencing in the goat (Capra hircus).
AB  - MicroRNAs (miRNAs) play a key role in many biological processes by regulating
      gene expression at the post-transcriptional level. A number of miRNAs have been
      identified from livestock species. However, compared with other animals, such as
      pigs and cows, the number of miRNAs identified in goats is quite low,
      particularly in hair follicles. In this study, to investigate the functional
      roles of miRNAs in goat hair follicles of goats with different coat colors, we
      sequenced miRNAs from two hair follicles samples (white and black) using Solexa
      sequencing. A total of 35,604,016 reads were obtained, which included 30,878,637
      clean reads (86.73%). MiRDeep2 software identified 214 miRNAs. Among them, 205
      were conserved among species and nine were novel miRNAs. Furthermore, DESeq
      software identified six differentially expressed miRNAs. Quantitative PCR
      confirmed differential expression of two miRNAs, miR-10b and miR-211. KEGG
      pathways were analyzed using the DAVID website for the predicted target genes of
      the differentially expressed miRNAs. Several signaling pathways including Notch
      and MAPK pathways may affect the process of coat color formation. Our study
      showed that the identified miRNAs might play an essential role in black and white
      follicle formation in goats. 

PMID- 24879526
TI  - Nipple discharge of CA15-3, CA125, CEA and TSGF as a new biomarker panel for
      breast cancer.
AB  - Breast cancer is the second leading cause of cancer death in women. Serum
      biomarkers such as cancer antigen 15-3 (CA15-3), cancer antigen 125 (CA125), and
      carcinoembryonic antigen (CEA) can be used as diagnostic and prognostic factors
      and can also provide valuable information during follow-up. However, serum
      protein biomarkers show limited diagnostic sensitivity and specificity in stand
      alone assays because their levels reflect tumor burden. To validate whether
      biomarkers in nipple discharge may serve as novel biomarkers for breast cancer,
      we composed a panel of potential cancer biomarkers, including CA15-3, CA125, CEA,
      and malignant tumor-specific growth factor (TSGF), and evaluated their expression
      in both serum and nipple discharge in order to explore the expression and
      significance of estrogen receptor (ER), progestrone receptor (PR), epidermal
      growth factor receptor type 2 (HER2/neu), CA15-3, CA125, CEA, and TSGF expression
      for their combined predictive value for breast cancer and in judging the
      prognosis of breast cancer. Univariate analysis revealed that combined detection
      of CA15-3, CA125, CEA, and TSGF in nipple discharge served as novel biomarkers
      for the diagnosis and prognosis of breast cancer, but in the multivariate
      analyses the adverse effects of the four biomarkers combination in nipple
      discharge positivity on overall survival were lost. Multivariate analysis
      revealed that the positivity of the combined detection of the four biomarkers in
      both nipple discharge and serum was significantly higher than that of other
      detection methods. Thus, the combined detection of these four biomarkers both in
      serum and nipple discharge was retained as an independent prognostic variable in
      breast cancer patients. Our results indicate that CA15-3, CA125, CEA, and TSGF in
      nipple discharge can serve as novel biomarkers in the diagnosis and prognosis of
      breast cancer. 

PMID- 24879527
TI  - New coumarins and anti-inflammatory constituents from the fruits of Cnidium
      monnieri.
AB  - The fruit of Cnidium monnieri is commercially used as healthcare products for the
      improvement of impotence and skin diseases. Three new coumarins, 3'-O
      methylmurraol (1), rel-(1'S,2'S)-1'-O-methylphlojodicarpin (2), and (1'S,2'S)-1'
      O-methylvaginol (3), have been isolated from the fruits of C. monnieri, together
      with 14 known compounds (4-17). The structures of these new compounds were
      determined through spectroscopic and MS analyses. Compounds 1, 4-12, and 14-17
      exhibited inhibition (IC50 <= 7.31 ug/mL) of superoxide anion generation by human
      neutrophils in response to formyl-l-methionyl-l-leucyl-l
      phenylalanine/cytochalasin B (fMLP/CB). Compounds 7, 9-11, 15, and 17 inhibited
      fMLP/CB-induced elastase release with IC50 values <=7.83 ug/mL. This
      investigation reveals that bioactive isolates (especially 6, 7, 14, and 17) could
      be further developed as potential candidates for the treatment or prevention of
      various inflammatory diseases. 

PMID- 24879528
TI  - Bioaccumulation of polybrominated diphenyl ethers (PBDEs) in Gammarus pulex:
      relative importance of different exposure routes and multipathway modeling.
AB  - Characterizing the exposure routes of an organism and its ability to regulate
      accumulated contaminants is a crucial step toward developing a biomonitor. To
      date, very little data are available on the bioaccumulation kinetics of PBDEs in
      freshwater biota. This study aims at investigating the potential use of a litter
      degrader widely distributed in European freshwaters, Gammarus pulex, as an
      indicator of exposure to PBDEs. In aquatic microcosms, gammarids were exposed to
      a mixture of brominated congeners (BDE-28, 47, 66, 85, 99, 100, 153, 154 and 183)
      to assess their ability to bioconcentrate PBDEs. Results show that all tested
      congeners are highly internalized by G. pulex and uptake rates of PBDEs are
      closely related to their partition coefficients (Kow). The determination of the
      elimination rate of BDE-47, the congener most readily accumulated by gammarids,
      indicated that metabolism and excretion of this congener are low in G. pulex,
      which argues in favor of its use as a quantitative biomonitor. Finally,
      bioaccumulation experiments were performed using contaminated leaves to determine
      the relative importance of dietary uptake in the contamination of gammarids. Even
      though water is the preeminent exposure route, a significant uptake of BDE-47
      through food was observed (27%). We propose a biodynamic model that takes into
      account both exposure routes to describe BDE-47 bioaccumulation. This study
      supports the use of this ubiquitous amphipod as an early warning monitor of the
      bioavailable contamination of freshwaters by PBDEs. 

PMID- 24879530
TI  - Electronic medical record: a balancing act of patient safety, privacy and health
      care delivery.
AB  - With almost $35 billion appropriated in government incentives and additional
      funds spent in development by institutions, the concept of an electronic patient
      record (EPR) within integrated health information technology (HIT) systems has
      taken the United States by storm. However, the United Kingdom's expensive
      struggle to implement a seamless EPR highlights the variety of pitfalls and
      unforeseen complications ranging from recognizing the importance of accurately
      assessing EPR-related patient risks to understanding the difficulties in the
      exchange of information across a gradient of distinct interfaces. Furthermore,
      the tenuous relationship between HIT implementation and patient outcomes in the
      short-term draws into question the value of EPR construction costs along with the
      ethical and privacy issues they create. Nonetheless, experts agree that with
      future software advances and physician familiarization, a robust HIT will be an
      important asset to patient autonomy, epidemiologic and clinical research,
      evidence-based error reduction and the potential for cost reduction. This article
      seeks to review the current status of this initiative and potential pitfalls that
      remain.

PMID- 24879529
TI  - Cavernous malformations of the central nervous system (CNS) in children: clinico
      radiological features and management outcomes of 36 cases.
AB  - BACKGROUND: Cavernous malformations (CMs) of the central nervous system (CNS) are
      angiographically occult vascular lesions that affect approximately 0.5 % of the
      general population, and one quarter of all CMs occurs in children. METHODS: We
      retrospectively analyzed demographic, clinical, radiological, management, and
      follow-up data of 36 pediatric patients with CMs from a single institution.
      RESULTS: The mean age of the children at first presentation and at operation was
      8.7 and 9.6 years, respectively. However, a bimodal age distribution was found
      with peak under 4 years and above 12 years. Seizure was the most common single
      presenting symptom (38.9 %), and 61.1 % of patients had at least one seizure
      before the admission. Focal neurological deficits (410.7 %), intracranial
      hypertension (27.8 %), and headache (2.8 %) were the other manifestations.
      Acute/subacute hemorrhage was evident at presentation in 63.9 %. The patients
      under 6 years of age were found to have significantly more giant cavernomas (69
      vs 20 %; p = 0.011), and more overt hemorrhages (81 vs 47 %; p = 0.065) at
      diagnosis than those patients above 12 years. Surgery was performed in 31
      patients (32 CMs), with 26 total and 6 incomplete resections. Mean follow-up
      duration was 6.9 +/- 4.1 years. Of all patients, 63.8 % had excellent and 30.5 %
      had good clinical outcomes, and also 90.9 % of the epileptic patients were
      seizure-free (Engel Class I) at the last follow-up. CONCLUSIONS: Younger children
      tend to harbor larger CMs and present with hemorrhage more frequently than older
      ones. Microsurgical resection should be the treatment of choice in symptomatic
      and accessible CMs.

PMID- 24879531
TI  - Prevalence, trends and functional impairment associated with reduced estimated
      glomerular filtration rate and albuminuria among the oldest-old U.S. adults.
AB  - BACKGROUND: The prevalence of reduced estimated glomerular filtration rate (eGFR)
      among U.S. adults aged 80 years and older increased between 1988 to 1994 and 2005
      to 2010. Trends in the prevalence of albuminuria over this time period have not
      been reported in this population. METHODS: We conducted a cross-sectional
      analysis of U.S. adults aged 80 years and older in the National Health and
      Nutrition Examination Survey 1988 to 1994 (n = 1020), 1999 to 2004 (n = 995) and
      2005 to 2010 (n = 971) to calculate the prevalence of albuminuria (albumin-to
      creatinine ratio [ACR] >=30 mg/g) by calendar period. The number of U.S. adults
      aged 80 years and older with elevated ACR and separately reduced eGFR was
      calculated by calendar period. RESULTS: Among participants aged 80 years and
      older, the prevalence of albuminuria was 30.9%, 33.0% and 30.6% in 1988 to 1994,
      1999 to 2004 and 2005 to 2010 (P = 0.9). The proportion of U.S. adults aged 80
      years and older with both eGFR <45 ml/min/1.73 m and ACR >=30 mg/g increased from
      6.8% in 1988 to 1994 to 8.4% and 9.5% in 1999 to 2004 and 2005 to 2010,
      respectively (P = 0.008). In 1988 to 1994, 1999 to 2004 and 2005 to 2010, there
      were 1.78 (95% confidence interval [CI], 1.29-2.27), 2.35 (95% CI, 1.93-2.78) and
      2.74 (95% CI, 2.32-3.16) million U.S. adults aged 80 years older with albuminuria
      and 2.34 (95% CI, 1.79-2.89), 3.55 (95% CI, 2.96-4.14) and 4.58 (95% CI, 3.87
      5.28) million, respectively, with eGFR <60 ml/min/1.73 m. CONCLUSIONS: The
      proportion of U.S. adults aged 80 years and older with an elevated ACR remained
      relatively stable between 1988 to 1994 and 2005 to 2010. However, due to the
      growth of the oldest-old, the absolute number with albuminuria increased
      substantially over the past 2 decades.

PMID- 24879532
TI  - 'Clickable' 2,5-diketopiperazines as scaffolds for ligation of biomolecules:
      their use in Abeta inhibitor assembly.
AB  - The synthesis of 1,3,6-trisubstituted-2,5-diketopiperazine scaffolds bearing up
      to three 'clickable' sites for further oxime bond or alkyne-azide cycloaddition
      ligations is described. The orthogonally Boc/Alloc protected DKP precursors
      prepared from L-lysine residues and an aminohexyl arm are efficiently prepared on
      a gram scale by sequentially using Fukuyama-Mitsunobu alkylation, dipeptide
      coupling and diketopiperazine ring formation as key steps. These scaffolds, with
      their glyoxylyl, aminooxy, alkynyl or azido functions, are "ready-to-use"
      platforms for biomolecular assembly. Their potentiality in this field was proved
      through the chemoselective ligation of Abeta-binding motifs, the KLVFFA peptide
      and the curcumin molecule. The inhibitory effect of these conjugates on Abeta
      amyloid fibril formation is reported using thioflavin T fluorescence assays and
      AFM observation.

PMID- 24879534
TI  - Clinical Course Score (CCS): a new clinical score to evaluate efficacy of
      neurotrauma treatment in traumatic brain injury and subarachnoid hemorrhage.
AB  - BACKGROUND: Neurotrauma continues to represent a challenging public health issue
      requiring continual improvement in therapeutic approaches. As no such current
      system exists, we present in this study the Clinical Course Score (CCS) as a new
      clinical score to evaluate the efficacy of neurotrauma treatment. METHODS: The
      CCS was calculated in neurotrauma patients to be the difference between the grade
      of the Glasgow Outcome Scale 6 months after discharge from our department and the
      grade of a 1 to 5 point reduced Glasgow Coma Scale on admission. We assessed the
      CCS in a total of 248 patients (196 traumatic brain injury [TBI] patients and 52
      subarachnoid hemorrhage [SAH] patients) who were treated in our Department of
      Neurosurgery between January 2011 and December 2012. RESULTS: We found negative
      CCS grades both in mild TBI and in mild SAH patients. In patients with severe TBI
      or SAH, we found positive CCS grades. In SAH patients, we found higher CCS scores
      in younger patients compared with elderly subjects in both mild and severe cases.
      CONCLUSIONS: The CCS can be useful in evaluating different therapeutic approaches
      during neurotrauma therapy. This new score might improve assessment of beneficial
      effects of therapeutic procedures.

PMID- 24879533
TI  - Identification of direct targets of transcription factor MYB46 provides insights
      into the transcriptional regulation of secondary wall biosynthesis.
AB  - Secondary wall formation requires coordinated transcriptional regulation of the
      genes involved in the biosynthesis of the components of secondary wall.
      Transcription factor (TF) MYB46 (At5g12870) has been shown to function as a
      central regulator for secondary wall formation in Arabidopsis thaliana,
      activating biosynthetic genes as well as the TFs involved in the pathways.
      Recently, we reported that MYB46 directly regulates secondary wall-associated
      cellulose synthase (CESA4, CESA7, and CESA8) and a mannan synthase (CSLA9) genes.
      However, it is not known whether MYB46 directly activates the biosynthetic genes
      for hemicellulose and lignin, which are the other two major components of
      secondary wall. Based on the observations that the promoter regions of many of
      the secondary wall biosynthetic genes contain MYB46-binding cis-regulatory
      motif(s), we hypothesized that MYB46 directly regulates the genes involved in the
      biosynthesis of the secondary wall components. In this report, we describe
      several lines of experimental evidence in support of the hypothesis.
      Electrophoretic mobility shift assay and chromatin immunoprecipitation analysis
      showed that MYB46 directly binds to the promoters of 13 genes involved in lignin
      and xylan biosynthesis. We then used steroid receptor-based inducible activation
      system to confirm that MYB46 directly activates the transcription of the xylan
      and lignin biosynthetic genes. Furthermore, ectopic up-regulation of MYB46
      resulted in a significant increase in xylose and a small increase in lignin
      content based on acetyl bromide soluble lignin measurements in Arabidopsis. Taken
      together, we conclude that MYB46 function as a central and direct regulator of
      the genes involved in the biosynthesis of all three major secondary wall
      components. 

PMID- 24879535
TI  - New insights into the benefits of exercise for muscle health in patients with
      idiopathic inflammatory myositis.
AB  - With recommended treatment, a majority with idiopathic inflammatory myopathy
      (IIM) develop muscle impairment and poor health. Beneficial effects of exercise
      have been reported on muscle performance, aerobic capacity and health in chronic
      polymyositis and dermatomyositis and to some extent in active disease and
      inclusion body myositis (IBM). Importantly, randomized controlled trials (RCTs)
      indicate that improved health and decreased clinical disease activity could be
      mediated through increased aerobic capacity. Recently, reports seeking mechanisms
      underlying effects of exercise in skeletal muscle indicate increased aerobic
      capacity (i.e. increased mitochondrial capacity and capillary density, reduced
      lactate levels), activation of genes in aerobic phenotype and muscle growth
      programs, and down regulation in genes related to inflammation. Altogether,
      exercise contributes to both systemic and within-muscle adaptations demonstrating
      that exercise is fundamental to improve muscle performance and health in IIM.
      There is a need for RCTs to study effects of exercise in active disease and IBM. 

PMID- 24879536
TI  - Oxygen-linked S-nitrosation in fish myoglobins: a cysteine-specific tertiary
      allosteric effect.
AB  - The discovery that cysteine (Cys) S-nitrosation of trout myoglobin (Mb) increases
      heme O2 affinity has revealed a novel allosteric effect that may promote hypoxia
      induced nitric oxide (NO) delivery in the trout heart and improve myocardial
      efficiency. To better understand this allosteric effect, we investigated the
      functional effects and structural origin of S-nitrosation in selected fish Mbs
      differing by content and position of reactive cysteine (Cys) residues. The Mbs
      from the Atlantic salmon and the yellowfin tuna, containing two and one reactive
      Cys, respectively, were S-nitrosated in vitro by reaction with Cys-NO to generate
      Mb-SNO to a similar yield (~0.50 SH/heme), suggesting reaction at a specific Cys
      residue. As found for trout, salmon Mb showed a low O2 affinity (P50 = 2.7 torr)
      that was increased by S-nitrosation (P50 = 1.7 torr), whereas in tuna Mb, O2
      affinity (P50 = 0.9 torr) was independent of S-nitrosation. O2 dissociation rates
      (koff) of trout and salmon Mbs were not altered when Cys were in the SNO or N
      ethylmaleimide (NEM) forms, suggesting that S-nitrosation should affect O2
      affinity by raising the O2 association rate (kon). Taken together, these results
      indicate that O2-linked S-nitrosation may occur specifically at Cys107, present
      in salmon and trout Mb but not in tuna Mb, and that it may relieve protein
      constraints that limit O2 entry to the heme pocket of the unmodified Mb by a yet
      unknown mechanism. UV-Vis and resonance Raman spectra of the NEM-derivative of
      trout Mb (functionally equivalent to Mb-SNO and not photolabile) were identical
      to those of the unmodified Mb, indicating that S-nitrosation does not affect the
      extent or nature of heme-ligand stabilization of the fully ligated protein. The
      importance of S-nitrosation of Mb in vivo is confirmed by the observation that Mb
      SNO is present in trout hearts and that its level can be significantly reduced by
      anoxic conditions. 

PMID- 24879537
TI  - Eldercare in the transnational setting: insights from Bangladeshi transnational
      families in the United States.
AB  - Little is known about the emotional impact of caregiving for elderly parents on
      migrant child in the transnational setting. To address this gap in the
      literature, this study examines the stressors, mediators, and outcomes of
      eldercare in the transnational context. Data were collected from 21 Bangladeshi
      immigrant men and women living in the United States who had living parents in
      Bangladesh over 60 years old. Despite the geographic distance, the migrants
      provide care to their parents such as emotional support, financial assistance,
      and arranging for care. While the health status of the care recipients
      contributed to primary objective stressors, none of the transnational caregivers'
      narratives reflected the presence of any subjective stressors such as role
      overload, role captivity, and relational deprivation. Distance and depending on
      others for hands-on caregiving resulted in feelings of loss of control over the
      caregiving process. Caregivers experienced a range of emotions from guilt,
      excessive worrying, and distress over the unpredictability and uncertainty of
      their circumstances. Kin networks, communicative technologies, and a cultural
      norm of filial piety contributed to mediating stress. The findings underscore the
      importance of supportive institutional policies such as visa and travel policies,
      employment leave, and counseling services for caregivers who provide care for
      their elderly parents transnationally. 

PMID- 24879539
TI  - A validated assay to quantitate serotonin in lamb plasma using ultrahigh
      performance liquid chromatography-tandem mass spectrometry: applications with
      LC/MS3.
AB  - An ultrahigh-performance liquid chromatography-tandem mass spectrometry
      (UHPLC/MS/MS) method was developed and validated for the quantification of
      serotonin (5-HT) in lamb plasma using [(2)d(4)]-serotonin ([(2)d(4)]-5-HT) as an
      internal standard. Charcoal-stripped human plasma was used as the blank matrix
      during validation, and 5-HT was quantitated using selected reaction monitoring.
      The UHPLC/MS/MS system consisted of an Agilent 1290 Infinity ultrahigh
      performance liquid chromatograph coupled with an AB SCIEX QTRAP((r)) 5500 hybrid
      linear ion trap triple quadrupole mass spectrometer. The method was validated for
      accuracy, precision, linearity, lower limit of quantification (LLOQ),
      selectivity, and other parameters. The LLOQ was 1.0 ng/mL, requiring 100 MUL of
      sample. The method was applied to monitor the 5-HT levels in lamb plasma after
      the administration of fluoxetine. Tandem mass spectrometry cubed (MS(3))
      experiments were also performed to investigate the fragmentation pattern of 5-HT
      and [(2)d(4)]-5-HT. A liquid chromatography-MS(3) (LC/MS(3)) method was
      developed, and the UHPLC/MS/MS and the LC/MS(3) methods were compared for
      performance.

PMID- 24879538
TI  - Measurement of meropenem concentration in different human biological fluids by
      ultra-performance liquid chromatography-tandem mass spectrometry.
AB  - Meropenem is a broad-spectrum antibiotic, often used for the empirical treatment
      of infections in critically ill patients with acute kidney injury. Meropenem has
      clinically insignificant protein binding and, as a carbapenem antibiotic, shows
      time-dependent bacterial killing, meaning that the unbound or free antibiotic
      concentration in blood should be maintained above the minimal inhibitory
      concentration of the pathogen for at least 40 % of the dosing interval. We
      developed and validated simple chromatographic methods by ultra-performance
      liquid chromatography-tandem mass spectrometry to measure plasma, filtrate
      dialysate, and urine concentrations of meropenem. Chromatographic separation was
      achieved using an Acquity((r)) UPLC((r)) BEH(TM) (2.1 * 100 mm id, 1.7 MUm)
      reverse-phase C(18) column, with a water/acetonitrile linear gradient containing
      0.1 % formic acid at a 0.4-mL/min flow rate. Meropenem and its internal standard
      (ertapenem) were detected by electrospray ionization mass spectrometry in
      positive ion multiple reaction monitoring mode. The limits of quantification were
      0.27, 0.24, and 1.22 mg/L, and linearity was observed between 0.27-150, 0.24-150,
      and 1.22-2,000 mg/L for plasma, filtrate-dialysate, and urine samples,
      respectively. Coefficients of variation and relative biases were less than 13.5
      and 8.0 % for all biological fluids. Recovery values were greater than 68.3 %.
      Evaluation of the matrix effect showed ion suppression for meropenem and
      ertapenem. No carry-over was observed. The validated methods are useful for both
      therapeutic drug monitoring and pharmacokinetic studies. It could be applied to
      daily clinical laboratory practice to measure the concentration of meropenem in
      plasma, filtrate-dialysate, and urine.

PMID- 24879540
TI  - Substrate and product role in the Shvo's catalyzed selective hydrogenation of the
      platform bio-based chemical 5-hydroxymethylfurfural.
AB  - The bio-based substrate and target product 2,5-bishydroxymethylfuran (BHMF)
      demonstrated to influence the reaction kinetics in the homogeneous reduction of 5
      hydroxymethylfurfural (HMF) catalyzed by the Ru-based Shvo's catalyst. A combined
      experimental and computational study supports an important role of the -CH2OH
      moiety which may be involved in the catalytic cycle toward the formation of
      different intermediates from HMF and BHMF. The reaction is selective and leads to
      quantitative formation of BHMF working under mild conditions. Furthermore, an
      optimized recycling procedure which avoids the use of water, allows recover and
      reuse of the catalyst without loss of activity. The mechanistic insights from
      this work may be extended to provide a general description of the chemistry of
      the Shvo's catalyst feeding further bio-based molecules. 

PMID- 24879541
TI  - Investigation of indolglyoxamide and indolacetamide analogues of polyamines as
      antimalarial and antitrypanosomal agents.
AB  - Pure compound screening has previously identified the indolglyoxy
      lamidospermidine ascidian metabolites didemnidine A and B (2 and 3) to be weak
      growth inhibitors of Trypanosoma brucei rhodesiense (IC50 59 and 44 MUM,
      respectively) and Plasmodium falciparum (K1 dual drug resistant strain) (IC50 41
      and 15 MUM, respectively), but lacking in selectivity (L6 rat myoblast, IC50 24
      MUM and 25 MUM, respectively). To expand the structure-activity relationship of
      this compound class towards both parasites, we have prepared and biologically
      tested a library of analogues that includes indoleglyoxyl and indoleacetic
      "capping acids", and polyamines including spermine (PA3-4-3) and extended
      analogues PA3-8-3 and PA3-12-3. 7-Methoxy substituted indoleglyoxylamides were
      typically found to exhibit the most potent antimalarial activity (IC50 10-92 nM)
      but with varying degrees of selectivity versus the L6 rat myoblast cell line. A 6
      methoxyindolglyoxylamide analogue was the most potent growth inhibitor of T.
      brucei (IC50 0.18 MUM) identified in the study: it, however, also exhibited poor
      selectivity (L6 IC50 6.0 MUM). There was no apparent correlation between
      antimalarial and anti-T. brucei activity in the series. In vivo evaluation of one
      analogue against Plasmodium berghei was undertaken, demonstrating a modest 20.9%
      reduction in parasitaemia. 

PMID- 24879543
TI  - New prenylxanthones from the deep-sea derived fungus Emericella sp. SCSIO 05240.
AB  - Four new prenylxanthones, emerixanthones A-D (1-4), together with six known
      analogues (5-10), were isolated from the culture of the deep-sea sediment derived
      fungus Emericella sp. SCSIO 05240, which was identified on the basis of
      morphology and ITS sequence analysis. The newstructures were determined by NMR
      (1H, 13C NMR, HSQC, HMBC, and 1H-1H COSY), MS, CD, and optical rotation analysis.
      The absolute configuration of prenylxanthone skeleton was also confirmed by the X
      ray crystallographic analysis. Compounds 1and 3 showed weak antibacterial
      activities, and 4 displayed mild antifungal activities against agricultural
      pathogens. 

PMID- 24879542
TI  - Marennine, promising blue pigments from a widespread Haslea diatom species
      complex.
AB  - In diatoms, the main photosynthetic pigments are chlorophylls a and c,
      fucoxanthin, diadinoxanthin and diatoxanthin. The marine pennate diatom Haslea
      ostrearia has long been known for producing, in addition to these generic
      pigments, a water-soluble blue pigment, marennine. This pigment, responsible for
      the greening of oysters in western France, presents different biological
      activities: allelopathic, antioxidant, antibacterial, antiviral, and growth
      inhibiting. A method to extract and purify marennine has been developed, but its
      chemical structure could hitherto not be resolved. For decades, H. ostrearia was
      the only organism known to produce marennine, and can be found worldwide. Our
      knowledge about H. ostrearia-like diatom biodiversity has recently been extended
      with the discovery of several new species of blue diatoms, the recently described
      H. karadagensis, H. silbo sp. inedit. and H. provincialis sp. inedit. These blue
      diatoms produce different marennine-like pigments, which belong to the same
      chemical family and present similar biological activities. Aside from being a
      potential source of natural blue pigments, H. ostrearia-like diatoms thus present
      a commercial potential for aquaculture, cosmetics, food and health industries. 

PMID- 24879544
TI  - Zn-driven discovery of a hydrothermal vent fungal metabolite clavatustide C, and
      an experimental study of the anti-cancer mechanism of clavatustide B.
AB  - A naturally new cyclopeptide, clavatustide C, was produced as a stress metabolite
      in response to abiotic stress elicitation by one of the hydrothermal vent fluid
      components Zn in the cultured mycelia of Aspergillus clavatus C2WU, which were
      isolated from Xenograpsus testudinatus. X. testudinatus lives at extreme, toxic
      habitat around the sulphur-rich hydrothermal vents in Taiwan Kueishantao. The
      known compound clavatustide B was also isolated and purified. This is the first
      example of a new hydrothermal vent microbial secondary metabolite produced in
      response to abiotic Zn treatment. The structures were established by
      spectroscopic means. The regulation of G1-S transition in hepatocellular
      carcinoma cell lines by clavatustide B was observed in our previous study. The
      purpose of the present study was to verify these results in other types of cancer
      cell lines and elucidate the possible molecular mechanism for the anti-cancer
      activities of clavatustide B. In different human cancer cell lines, including
      pancreatic cancer (Panc-1), gastric cancer (MGC-803), colorectal cancer (SW-480),
      retinoblastoma (WERI-Rb-1) and prostate cancer (PC3), clavatustide B efficiently
      suppressed cell proliferations in a dose-dependent manner. Although different
      cancer cell lines presented variety in Max effect dose and IC50 dose, all cancer
      cell lines showed a lower Max effect dose and IC50 dose compared with human
      fibroblasts (hFB) (p < 0.05). Moreover, significant accumulations in G1 phases
      and a reduction in S phases (p < 0.05) were observed under clavatustide B
      treatment. The expression levels of 2622 genes including 39 cell cycle-associated
      genes in HepG2 cells were significantly altered by the treatment with 15 MUg/mL
      clavatustide B after 48 h. CCNE2 (cyclin E2) was proved to be the key regulator
      of clavatustide B-induced G1-S transition blocking in several cancer cell lines
      by using real-time PCR. 

PMID- 24879545
TI  - Profiling of polar lipids in marine oleaginous diatom Fistulifera solaris JPCC
      DA0580: prediction of the potential mechanism for eicosapentaenoic acid
      incorporation into triacylglycerol.
AB  - The marine oleaginous diatom Fistulifera solaris JPCC DA0580 is a candidate for
      biodiesel production because of its high lipid productivity. However, the
      substantial eicosapentaenoic acid (EPA) content in this strain would affect the
      biodiesel quality. On the other hand, EPA is also known as the essential health
      supplement for humans. EPAs are mainly incorporated into glycerolipids in the
      microalgal cell instead of the presence as free fatty acids. Therefore, the
      understanding of the EPA biosynthesis including the incorporation of the EPA into
      glycerolipids especially triacylglycerol (TAG) is fundamental for regulating EPA
      content for different purposes. In this study, in order to identify the
      biosynthesis pathway for the EPA-containing TAG species, a lipidomic
      characterization of the EPA-enriched polar lipids was performed by using direct
      infusion electrospray ionization (ESI)-Q-TRAP-MS and MS/MS analyses. The
      determination of the fatty acid positional distribution showed that the sn-2
      position of all the chloroplast lipids and part of phosphatidylcholine (PC)
      species was occupied by C16 fatty acids. This result suggested the critical role
      of the chloroplast on the lipid synthesis in F. solaris. Furthermore, the
      exclusive presence of C18 fatty acids in PC highly indicated the biosynthesis of
      EPA on PC. Finally, the PC-based acyl-editing and head group exchange processes
      were proposed to be essential for the incorporation of EPA into TAG and
      chloroplast lipids. 

PMID- 24879547
TI  - Age, sex, and symptom intensity influence test taking parameters on functional
      patient-reported outcomes.
AB  - OBJECTIVE: Item response theory-based patient-reported outcomes such as the
      Activity Measure for Post Acute Care Computerized Adaptive Test are gaining use
      because of their flexibility and ease of administration. Their psychometric
      properties are being explored, but little is known about how respondent
      characteristics may impact precision. The goal of this study was, therefore, to
      assess the effects of age, sex, and symptom intensity on respondents' test taking
      behaviors and scores. DESIGN: Three hundred eleven adults with late-stage lung
      cancer were consecutively enrolled between April 2008 and April 2009.
      Demographics and comorbidities were abstracted from their electronic medical
      records. The participants were followed on a 3- to 4-wk basis by telephonic
      interviews that involved administration of the Activity Measure for Post Acute
      Care Computerized Adaptive Test, followed by numerical rating scales scoring of
      their pain, fatigue, and dyspnea. RESULTS: In more than 2538 computerized
      adaptive test (CAT) sessions, three findings were prominent. First, the women and
      the older patients took longer to complete CAT sessions, were more likely to skip
      items, and produced scores with larger standard errors. Second, the respondents
      with higher levels of dyspnea and fatigue, but not pain, completed their CAT
      sessions more rapidly and were less likely to skip items. Third, fatigue and
      dyspnea interact with age but not sex to influence CAT duration and skip count.
      CONCLUSIONS: The findings of this study suggest that certain common clinical
      populations, for example, women, geriatric patients, and patients with intense
      symptoms, differ systematically in the time they are willing to devote to testing
      and the precision of their responses. The latter finding, unstable precision, is
      unlikely to be CAT specific and has implications for the interpretation of the
      scores of the Activity Measure for Post Acute Care Computerized Adaptive Test and
      other patient-reported outcomes.

PMID- 24879546
TI  - Ilimaquinone and ethylsmenoquinone, marine sponge metabolites, suppress the
      proliferation of multiple myeloma cells by down-regulating the level of beta
      catenin.
AB  - Deregulation of Wnt/beta-catenin signaling promotes the development of a broad
      range of human cancers, including multiple myeloma, and is thus a potential
      target for the development of therapeutics for this disease. Here, we used a cell
      based reporter system to demonstrate that ilimaquinone and ethylsmenoquinone
      (formerly smenorthoquinone), sesquiterpene-quinones from a marine sponge,
      inhibited beta-catenin response transcription induced with Wnt3a-conditioned
      medium, by down-regulating the level of intracellular beta-catenin.
      Pharmacological inhibition of glycogen synthase kinase-3beta did not abolish the
      ilimaquinone and ethylsmenoquinone-mediated beta-catenin down-regulation.
      Degradation of beta-catenin was consistently found in RPMI-8226 multiple myeloma
      cells after ilimaquinone and ethylsmenoquinone treatment. Ilimaquinone and
      ethylsmenoquinone repressed the expression of cyclin D1, c-myc, and axin-2, which
      are beta-catenin/T-cell factor-dependent genes, and inhibited the proliferation
      of multiple myeloma cells. In addition, ilimaquinone and ethylsmenoquinone
      significantly induced G0/G1 cell cycle arrest and apoptosis in RPMI-8266 cells.
      These findings suggest that ilimaquinone and ethylsmenoquinone exert their anti
      cancer activity by blocking the Wnt/beta-catenin pathway and have significant
      potential as therapies for multiple myeloma. 

PMID- 24879548
TI  - Neuromuscular electrical stimulation induces beneficial adaptations in the
      extracellular matrix of quadriceps muscle after anterior cruciate ligament
      transection of rats.
AB  - OBJECTIVE: The aim of this study was to assess the effect of neuromuscular
      electrical stimulation (NMES) on the extracellular matrix remodeling of the
      quadriceps muscle after anterior cruciate ligament (ACL) transection in rats. The
      hypothesis of this study was that ACL transection would induce maladaptive
      modifications in the extracellular matrix through the increase in connective
      tissue (CT) accumulation and net degradation of type IV collagen of the
      quadriceps muscle. In addition, clinical-like NMES, applied to the quadriceps
      muscle immediately after the ACL transection, would reduce the accumulation of
      the CT content and net degradation of type IV collagen. DESIGN: Wistar male rats
      were randomized into five different groups: ACL (surgery and ACL transection),
      Sham (surgery without ACL transection), ACLES (surgery, ACL transection, and
      NMES), ShamES (surgery without ACL transection, but NMES), and Control (intact
      animals). The vastus medialis, rectus femoris, and vastus lateralis muscles of
      the quadriceps were harvested 1, 2, 3, 7, and 15 days after surgery. Matrix
      metalloproteinase-2 (MMP-2) (messenger RNA [mRNA] levels and activity), collagen
      IV (mRNA and protein levels), and CT density were assessed. RESULTS: The ACL
      transection increased the CT content and MMP-2 mRNA levels and decreased collagen
      IV mRNA and protein levels. NMES minimized the CT density in all muscles and
      reduced the MMP-2 mRNA levels mainly in the vastus lateralis muscle at 7 days.
      Moreover, type IV collagen mRNA levels were increased in all muscles at 7 days,
      as was the protein level only at 15 days, in the NMES groups. CONCLUSIONS: This
      study showed that ACL transection increases CT content and MMP-2 mRNA levels and
      induces rapid changes in basement membranes, causing net degradation of type IV
      collagen during the first 2 wks after ACL injury. Furthermore, clinical-like NMES
      minimized the accumulation of CT density, regulated the MMP-2 mRNA levels, and
      increased both type IV collagen mRNA and protein levels.

PMID- 24879549
TI  - Association of early ambulation with length of stay and costs in total knee
      arthroplasty: retrospective cohort study.
AB  - OBJECTIVE: The objective of this study was to evaluate the association of early
      ambulation with length of stay, costs, and outcomes in inpatients undergoing
      total knee arthroplasty. DESIGN: This is a retrospective study of 1504 patients
      who underwent total knee arthroplasty between August 2009 and January 2011 in a
      tertiary teaching hospital. All patients commenced physiotherapy interventions on
      postoperative day 1. The patients were categorized into an early ambulation group
      (began ambulating on postoperative day 1; n = 803) or a late ambulation group
      (began ambulating on postoperative day 2; n = 701). Multivariable regression and
      propensity score analyses were used to reduce selection biases. RESULTS: Early
      ambulation was associated with a statistically significant reduction in the
      adjusted average length of stay (-0.44 day; P < 0.001) and adjusted average total
      hospitalization costs (Singapore, -$385; United States, -$315; P < 0.001). Both
      groups did not differ significantly in the 90-day readmission rate; however,
      early ambulation was associated with higher odds of achieving at least 90 degrees
      of knee flexion (adjusted odds ratio, 1.33; P < 0.01) and requiring a walking aid
      with a smaller base of support (adjusted proportional odds ratio, 1.36; P <
      0.001). CONCLUSIONS: As little as a 1-day difference in the day of first
      ambulation was associated with a shorter length of stay, lower hospitalization
      costs, and improved knee function. The results of this study provide the first
      empirical support for the usefulness of early ambulation after total knee
      arthroplasty.

PMID- 24879550
TI  - Effects of ethyl chloride spray on pain and parameters of needle electromyography
      in the upper extremity.
AB  - OBJECTIVE: The aim of this study was to compare the effects of ethyl chloride and
      placebo sprays for reducing pain induced by needle electromyography and changes
      in parameters of the motor unit action potential during needle electromyography
      of the upper extremity. DESIGN: Sixty patients were randomized into the ethyl
      chloride or placebo spray groups. In both groups, spray was applied just before
      needle electromyography of the flexor carpi radialis, and a visual analog scale
      to evaluate the pain of needle electromyography and a five-point Likert scale for
      patient satisfaction and preference for reexamination were compared between the
      two groups. Then, changes in the amplitude, phases, turns, and duration of the
      motor unit action potential during needle electromyography of the biceps brachii
      were compared before and after spraying in each group. RESULTS: The visual analog
      scale was significantly lower, and patient satisfaction and preference for
      reexamination were significantly higher in the ethyl chloride spray group. Among
      the parameters of the motor unit action potential, there were no significant
      changes except for an increased duration after spraying with ethyl chloride.
      CONCLUSIONS: Ethyl chloride spray can effectively reduce pain, but it must be
      used with caution because it may affect parameters of the motor unit action
      potential during needle electromyography.

PMID- 24879551
TI  - Factors associated with pressure ulcer risk in spinal cord injury rehabilitation.
AB  - OBJECTIVE: The aim of this study was to identify patient and clinical factors
      most strongly associated with a spinal cord injury patient's risk for developing
      a pressure ulcer (PU) during rehabilitation. DESIGN: This is a prospective
      observational cohort study conducted at an urban rehabilitation hospital-based
      specialized spinal cord injury center. The main outcome measure was the onset of
      a stage 2 or higher PU. RESULTS: Study patients (N = 159) with new (n = 66) and
      patients with earlier (n = 99) spinal injuries had identical rates at which they
      acquired a new PU (stage >=2) in rehabilitation--13.1%. The patients who came to
      rehabilitation with a PU or myocutaneous flap exhibited a higher rate of
      developing yet another PU while in rehabilitation (30.2%) than those who came to
      rehabilitation without an existing PU or flap (6.9%). Logistic regression
      analysis identified two variables that best predicted a patient's risk at
      admission for developing a PU during rehabilitation (c = 0.77)--entering
      rehabilitation with a PU and admission Functional Independence Measure transfers
      score of less than 3.5. CONCLUSIONS: The greatest risk of developing a new PU in
      rehabilitation is being admitted with an existing PU followed by admission
      Functional Independence Measure transfers score of less than 3.5. Using these two
      variables, one can develop a patient PU risk algorithm at admission that can
      alert clinicians for the need to enhance vigilance, skin monitoring, and early
      patient education.

PMID- 24879552
TI  - Effect of extracorporeal shock wave therapy on gait pattern in hemiplegic
      cerebral palsy: a randomized controlled trial.
AB  - OBJECTIVE: The aim of this study was to investigate the effects of shock wave
      therapy on gait pattern in children with hemiplegic cerebral palsy. DESIGN:
      Fifteen children were assigned to the study group, whose members received shock
      wave therapy (1500 shots/muscle, frequency of 5Hz, energy of 0.030 mJ/mm, one
      session/wk). Another 15 were assigned to the control group, whose members
      participated in a conventional physical therapy exercise program for 3 successive
      months. Baseline and posttreatment assessments were performed using the Modified
      Ashworth Scale to evaluate spasticity degrees and using a three-dimensional gait
      analysis to evaluate gait parameters. RESULTS: Children in the study group showed
      a significant improvement when compared with those in the control group (P <
      0.005). The Modified Ashworth scores after treatment were 1.86 (0.22) and 1.63
      (0.23) for the control and study groups, respectively. The gait parameters
      (stride length, cadence, speed, cycle time, and stance phase percentage) after
      treatment were 0.5 m, 125 steps/min, 0.6 m/sec, 0.48 sec, and 50.4% and 0.74 m,
      119 steps/min, 0.75 m/sec, 0.65 sec, and 55.9% for the control group and the
      study group, respectively. CONCLUSIONS: Shock wave therapy may be a useful tool
      for improving spasticity and gait pattern in children with hemiplegic cerebral
      palsy.

PMID- 24879553
TI  - Intraarticular platelet-rich plasma injection in the treatment of knee
      osteoarthritis: review and recommendations.
AB  - Intraarticular platelet-rich plasma (PRP) injection has emerged as a promising
      treatment for knee osteoarthritis. Studies to date, including multiple randomized
      controlled trials, have shown that PRP is a safe and effective treatment option
      for knee osteoarthritis. Intraarticular PRP is similar in efficacy to hyaluronic
      acid, and seems to be more effective than hyaluronic acid in younger, active
      patients with low-grade osteoarthritis. Treatment benefits seem to wane after 6-9
      mos. There are numerous PRP treatment variables that may be of importance, and
      the optimal PRP protocol remains unclear. Future investigations should control
      and analyze the effects of these variables in PRP treatment. High-quality
      randomized controlled trials are needed to optimize PRP treatment methods and
      better define the role of PRP in osteoarthritis management in the knee and,
      potentially, in other joints. 

PMID- 24879554
TI  - Regenerating skeletal muscle in the face of aging and disease.
AB  - Skeletal muscle is a fundamental organ in the generation of force and movement,
      the regulation of whole-body metabolism, and the provision of resiliency. Indeed,
      physical medicine and rehabilitation is recognized for optimizing skeletal muscle
      health in the context of aging (sarcopenia) and disease (cachexia). Exercise is,
      and will remain, the cornerstone of therapies to improve skeletal muscle health.
      However, there are now a number of promising biologic and small molecule
      interventions currently under development to rejuvenate skeletal muscle,
      including myostatin inhibitors, selective androgen receptor modulators, and an
      activator of the fast skeletal muscle troponin complex. The opportunities for
      skeletal muscle-based regenerative therapies and a selection of emerging
      pharmacologic interventions are discussed in this review. 

PMID- 24879555
TI  - Cuff deflation: rehabilitation in critical care.
AB  - This is a case series of rehabilitation failures that resulted in severe reactive
      depression from patients unnecessarily bereft of verbal communication by being
      left to breathe or be ventilated via tracheostomy tubes, with or without inflated
      cuffs, for months to years. 

PMID- 24879556
TI  - Congenital absence of the vas deferens and unilateral renal agenesis:
      implications for patient and family.
AB  - BACKGROUND AND AIMS: At routine groin surgery in male paediatric patients
      occasionally the vas deferens may be absent. This finding usually leads to
      investigations to establish the status of the contralateral vas deferens and the
      status of the kidneys. It is not uncommon to find either an ipsilateral renal
      agenesis or congenital bilateral absence of the vas deferens. The latter finding
      prompts a test for cystic fibrosis. We report three patients who upon
      investigation were found to have the rare combination of congenital bilateral
      absence of the vas deferens and unilateral renal agenesis, and discuss the
      possible embryological basis, the clinical management and the long-term
      implications of these findings. PATIENTS AND METHODS: We present three patients
      who were incidentally found to have absence of the vas deferens whilst undergoing
      elective groin surgery and following further tests were diagnosed with congenital
      bilateral absence of the vas deferens and unilateral renal agenesis. The case
      notes were reviewed, together with the results of radiological investigations,
      cystic fibrosis screening and the status of the contralateral vas deferens.
      RESULTS: All three patients were found to have congenital bilateral absence of
      the vas deferens, unilateral renal agenesis and were not found to have cystic
      fibrosis. CONCLUSIONS: The combination of congenital bilateral absence of the vas
      deferens and unilateral renal agenesis, without cystic fibrosis, is rare and not
      reported previously in the paediatric literature. These findings require
      appropriate counselling of the parents and child, with regards to the long-term
      implications of infertility and renal function.

PMID- 24879557
TI  - Penile strangulation by hair.
AB  - PURPOSE: To know the causes and results of treatment of complications from a
      penile strangulation by hair in seven boys. METHODS: From April 2000 to December
      2012, seven boys presenting serious penile complications by hair strangulation
      have been operated in two centers. All seven boys had transection of the urethra
      at the coronal level. And none of our patients were at the stage of necrosis or
      amputation of the glans. The age of the patients at surgery ranged from 34 to 134
      months (mean 96 months). RESULTS: Four children presented urethrocutaneous
      fistulas (57% of cases), and the innervation and vascularization of the glans
      remained poor after repair in three patients. CONCLUSION: The penile
      strangulation by hair was due to a simple accident. However, several predisposing
      factors were discovered in our patients: lack of cleanliness; a moist environment
      with nocturnal enuresis; the presence of pubic hair in young children reported in
      the four children, and a coronal sulcus not covered by the foreskin in
      circumcised children.

PMID- 24879558
TI  - Loss of transcriptional control over endogenous retroelements during
      reprogramming to pluripotency.
AB  - Endogenous retroelements (EREs) account for about half of the mouse or human
      genome, and their potential as insertional mutagens and transcriptional
      perturbators is suppressed by early embryonic epigenetic silencing. Here, we
      asked how ERE control is maintained during the generation of induced pluripotent
      stem cells (iPSCs), as this procedure involves profound epigenetic remodeling. We
      found that all EREs tested were markedly up-regulated during the reprogramming of
      either mouse embryonic fibroblasts, human CD34(+) cells, or human primary
      hepatocytes. At the iPSC stage, EREs of some classes were repressed, whereas
      others remained highly expressed, yielding a pattern somewhat reminiscent of that
      recorded in embryonic stem cells. However, variability persisted between
      individual iPSC clones in the control of specific ERE integrants. Both during
      reprogramming and in iPS cells, the up-regulation of specific EREs significantly
      impacted on the transcription of nearby cellular genes. While transcription
      triggered by specific ERE integrants at highly precise developmental stages may
      be an essential step toward obtaining pluripotent cells, the broad and unspecific
      unleashing of the repetitive genome observed here may contribute to the
      inefficiency of the reprogramming process and to the phenotypic heterogeneity of
      iPSCs. 

PMID- 24879560
TI  - Mechanistic studies for tri-targeted inhibition of enzymes involved in
      cholesterol biosynthesis by green tea polyphenols.
AB  - In the present study, we found that three enzymes, MVK, MDD and FPPS, in the
      mevalonate pathway (MVP) of cholesterol biosynthesis, can be simultaneously
      inhibited by two green tea polyphenols ((-)-epicatechin-3-gallate, ECG; (-)
      epigallocatechin-3-gallate, EGCG). Molecular dynamics simulations and
      pharmacophore studies were carried out to elucidate the tri-targeted inhibition
      mechanisms. Our results indicate that similar triangular binding pockets exist in
      all three enzymes, which is essential for their binding with polyphenols. Two
      distinct binding poses for ECG and EGCG were observed in our MD simulations.
      These results shed light on the potential for further selective and multi
      targeted inhibitor design for the treatment of hyperlipidemia. 

PMID- 24879559
TI  - Interplay of TRIM28 and DNA methylation in controlling human endogenous
      retroelements.
AB  - Reverse transcription-derived sequences account for at least half of the human
      genome. Although these retroelements are formidable motors of evolution, they can
      occasionally cause disease, and accordingly are inactivated during early
      embryogenesis through epigenetic mechanisms. In the mouse, at least for
      endogenous retroviruses, important mediators of this process are the tetrapod
      specific KRAB-containing zinc finger proteins (KRAB-ZFPs) and their cofactor
      TRIM28. The present study demonstrates that KRAB/TRIM28-mediated regulation is
      responsible for controlling a very broad range of human-specific endogenous
      retroelements (EREs) in human embryonic stem (ES) cells and that it exerts, as a
      consequence, a marked effect on the transcriptional dynamics of these cells. It
      further reveals reciprocal dependence between TRIM28 recruitment at specific
      families of EREs and DNA methylation. It finally points to the importance of
      persistent TRIM28-mediated control of ERE transcriptional impact beyond their
      presumed inactivation by DNA methylation. 

PMID- 24879561
TI  - Acute kidney injury caused by ceftriaxone-induced urolithiasis in children: a
      single-institutional experience in diagnosis, treatment and follow-up.
AB  - PURPOSE: To evaluate our clinical outcomes in managing acute kidney injury (AKI)
      resulting from ceftriaxone-induced urolithiasis with emergency treatment.
      METHODS: From July 2008 to July 2013, a series of 15 patients including 12 males
      and 3 females were admitted to our center. The mean age of them was (4.76 +/-
      3.74) years. A chief complaint of anuria was presented in 12 (80.0 %) patients
      for 13 h-4 days and that of oliguria in three (20.0 %) patients for 20 h-10 days.
      All of them were diagnosed of postrenal AKI resulting from ceftriaxone-induced
      urolithiasis and underwent emergency hospitalization. RESULTS: Double-J stenting
      with cystoscopy was successfully performed in nine patients (60.0 %), and
      ureteroscopy was applied in four patients (26.7 %). One patient (6.7 %) underwent
      unilateral double-J insertion combined with contralateral percutaneous
      nephrostomy, and one (6.7 %) underwent open surgery. Loose texture and sandlike
      stones, the main characteristics of these stones, made them excreted
      spontaneously after the initial treatment, whereas only one patient (6.7 %)
      underwent additional ureterolithotomy due to many residual calculi. Serum
      creatinine and blood urea nitrogen recovered to normal levels within 3 days. All
      specimens were collected and analyzed by infrared spectrum, with results
      demonstrating that the main composition was ceftriaxone calcique. All patients
      were followed up for 11 months-5 years (mean 33.80 +/- 22.56 months). No one
      turned to irreversible renal failure. CONCLUSIONS: Ceftriaxone could result in
      urolithiasis in children, which could also cause AKI. Appropriate and timely
      surgical management by conventional treatments will mostly lead to full recovery
      of renal functions.

PMID- 24879562
TI  - Spatial structuring of arbuscular mycorrhizal communities in benchmark and
      modified temperate eucalypt woodlands.
AB  - Arbuscular mycorrhizal fungi (AMF) are crucial to the functioning of the plant
      soil system, but little is known about the spatial structuring of AMF communities
      across landscapes modified by agriculture. AMF community composition was
      characterized across four sites in the highly cleared south-western Australian
      wheatbelt that were originally dominated by forb-rich eucalypt woodlands.
      Environmentally induced spatial structuring in AMF composition was examined at
      four scales: the regional scale associated with location, the site scale
      associated with past management (benchmark woodlands with no agricultural
      management history, livestock grazing, recent revegetation), the patch scale
      associated with trees and canopy gaps, and the fine scale associated with the
      herbaceous plant species beneath which soils were sourced. Field-collected soils
      were cultured in trap pots; then, AMF composition was determined by identifying
      spores and through ITS1 sequencing. Structuring was strongest at site scales,
      where composition was strongly related to prior management and associated changes
      in soil phosphorus. The two fields were dominated by the genera Funneliformis and
      Paraglomus, with little convergence back to woodland composition after
      revegetation. The two benchmark woodlands were characterized by Ambispora
      gerdemannii and taxa from Gigasporaceae. Their AMF communities were strongly
      structured at patch scales associated with trees and gaps, in turn most strongly
      related to soil N. By contrast, there were few patterns at fine scales related to
      different herbaceous plant species, or at regional scales associated with the 175
      km distance between benchmark woodlands. Important areas for future investigation
      are to identify the circumstances in which recolonization by woodland AMF may be
      limited by fungal propagule availability, reduced plant diversity and/or altered
      chemistry in agricultural soils.

PMID- 24879564
TI  - Loss of LRIG1 locus increases risk of early and late relapse of stage I/II breast
      cancer.
AB  - Gains and losses at chromosome 3p12-21 are common in breast tumors and associated
      with patient outcomes. We hypothesized that the LRIG1 gene at 3p14.1, whose
      product functions in ErbB-family member degradation, is a critical tumor modifier
      at this locus. We analyzed 971 stage I/II breast tumors using Affymetrix Oncoscan
      molecular inversion probe arrays that include 12 probes located within LRIG1.
      Copy number results were validated against gene expression data available in the
      public database. By partitioning the LRIG1 probes nearest exon 12/13, we confirm
      a breakpoint in the gene and show that gains and losses in the subregions differ
      by tumor and patient characteristics including race/ethnicity. In analyses
      adjusted for known prognostic factors, loss of LRIG1 was independently associated
      with risk of any relapse (HR, 1.90; 95% CI, 1.32-2.73), relapse>=5 years (HR,
      2.39; 95% CI, 1.31-4.36), and death (HR, 1.55; 95% CI, 1.11-2.16). Analyses of
      copy number across chromosome 3, as well as expression data from pooled, publicly
      available datasets, corroborated the hypothesis of an elevated and persistent
      risk among cases with loss of or low LRIG1. We concluded that loss/low expression
      of LRIG1 is an independent risk factor for breast cancer metastasis and death in
      stage I/II patients. Increased hazard in patients with loss/low LRIG1 persists
      years after diagnosis, suggesting that LRIG1 is acting as a critical suppressor
      of tumor metastasis and is an early clinical indicator of risk for late
      recurrences in otherwise low-risk patients.

PMID- 24879565
TI  - Mast cell-derived prostaglandin D2 inhibits colitis and colitis-associated colon
      cancer in mice.
AB  - Compared with prostaglandin E2, which has an established role in cancer, the role
      of the COX metabolite prostaglandin D2 (PGD2) in chronic inflammation leading to
      tumorigenesis is uncertain. In this study, we investigated the role of PGD2 in
      colitis and colitis-associated colon cancer (CAC) using genetically modified mice
      and an established model of inflammatory colon carcinogenesis. Systemic genetic
      deficiency in hematopoietic PGD synthase (H-PGDS) aggravated colitis and
      accelerated tumor formation in a manner associated with increased TNFalpha
      expression. Treatment with a TNFalpha receptor antagonist attenuated colitis
      regardless of genotype. Histologic analysis revealed that infiltrated mast cells
      strongly expressed H-PGDS in inflamed colons. Mast cell-specific H-PGDS
      deficiency also aggravated colitis and accelerated CAC. In contrast, treatment
      with a PGD2 receptor agonist inhibited colitis and CAC. Together, our results
      identified mast cell-derived PGD2 as an inhibitor of colitis and CAC, with
      implications for its potential use in preventing or treating colon cancer.

PMID- 24879566
TI  - Breast cancer risk after occupational solvent exposure: the influence of timing
      and setting.
AB  - Organic solvents are ubiquitous in occupational settings where they may
      contribute to risks for carcinogenesis. However, there is limited information on
      organic solvents as human breast carcinogens. We examined the relationship
      between occupational exposure to solvents and breast cancer in a prospective
      study of 47,661 women with an occupational history in the Sister Study cohort.
      Occupational solvent exposure was categorized using self-reported job-specific
      solvent use collected at baseline. Multivariable Cox regression analyses were
      used to assess breast cancer risk, adjusting for established breast cancer risk
      factors. A total of 1,798 women were diagnosed with breast cancer during follow
      up, including 1,255 invasive cases. Overall the risk of invasive breast cancer
      was not associated with lifetime exposure to solvents [HR, 1.04; 95% confidence
      interval (CI), 0.88-1.24]. Parous women who worked with solvents before their
      first full-term birth had an increased risk of estrogen receptor-positive
      invasive breast cancer compared with women who never worked with solvents (HR,
      1.39; 95% CI, 1.03-1.86). A significantly elevated risk for estrogen receptor
      positive invasive breast cancer was associated with solvent exposure among
      clinical laboratory technologists and technicians (HR, 2.00; 95% CI, 1.07-3.73).
      Occupational exposure to solvents before first birth, a critical period of breast
      tissue differentiation, may result in increased vulnerability for breast cancer.
      Our findings suggest a need for future studies in this area to focus on exposure
      time windows and solvent types in different occupational settings.

PMID- 24879567
TI  - Genomic rearrangements define lineage relationships between adjacent lepidic and
      invasive components in lung adenocarcinoma.
AB  - The development of adenocarcinoma of the lung is believed to proceed from in situ
      disease (adenocarcinoma in situ, AIS) to minimally invasive disease with
      prominent lepidic growth (minimally invasive adenocarcinoma, MIA), then to fully
      invasive adenocarcinoma (AD), but direct evidence for this model has been
      lacking. Because some lung adenocarcinomas show prominent lepidic growth (AD-L),
      we designed a study to address the lineage relationship between the lepidic
      (noninvasive) component (L) and the adjacent nonlepidic growth component
      representing invasive disease within individual tumors. Lineage relationships
      were evaluated by next-generation DNA sequencing to define large genomic
      rearrangements in microdissected tissue specimens collected by laser capture. We
      found a strong lineage relationship between the majority of adjacent lepidic and
      invasive components, supporting a putative AIS-AD transition. Notably, many
      rearrangements were detected in the less aggressive lepidic component, although
      the invasive component exhibited an overall higher rate of genomic rearrangement.
      Furthermore, a significant number of genomic rearrangements were present in
      histologically normal lung adjacent to tumor, but not in host germline DNA,
      suggesting field defects restricted to zonal regions near a tumor. Our results
      offer a perspective on the genetic pathogenesis underlying adenocarcinoma
      development and its clinical management.

PMID- 24879568
TI  - Do inflammatory markers portend heterotopic ossification and wound failure in
      combat wounds?
AB  - BACKGROUND: After a decade of war in Iraq and Afghanistan, we have observed an
      increase in combat-related injury survival and a paradoxical increase in injury
      severity, mainly because of the effects of blasts. These severe injuries have a
      devastating effect on each patient's immune system resulting in massive
      upregulation of the systemic inflammatory response. By examining inflammatory
      mediators, preliminary data suggest that it may be possible to correlate
      complications such as wound failure and heterotopic ossification (HO) with
      distinct systemic and local inflammatory profiles, but this is a relatively new
      topic. QUESTIONS/PURPOSES: We asked whether systemic or local markers of
      inflammation could be used as an objective means, independent of demographic and
      subjective factors, to estimate the likelihood of (1) HO and/or (2) wound failure
      (defined as wounds requiring surgical debridement after definitive closure, or
      wounds that were not closed or covered within 21 days of injury) in patients
      sustaining combat wounds. METHODS: Two hundred combat wounded active-duty service
      members who sustained high-energy extremity injuries were prospectively enrolled
      between 2008 and 2012. Of these 200 patients, 189 had adequate followups to
      determine the presence or absence of HO, and 191 had adequate followups to
      determine the presence or absence of wound failure. In addition to injury
      specific and demographic data, we quantified 24 cytokines and chemokines during
      each debridement. Patients were followed clinically for 6 weeks, and radiographs
      were obtained 3 months after definitive wound closure. Associations were
      investigated between these markers and wound failure or HO, while controlling for
      known confounders. RESULTS: The presence of an amputation (p < 0.001; odds ratio
      [OR], 6.1; 95% CI. 1.63-27.2), Injury Severity Score (p = 0.002; OR, 33.2; 95%
      CI, 4.2-413), wound surface area (p = 0.001; OR, 1.01; 95% CI, 1.002-1.009),
      serum interleukin (IL)-3 (p = 0.002; OR, 2.41; 95% CI, 1.5-4.5), serum IL-12p70
      (p = 0.01; OR, 0.49; 95% CI, 0.27-0.81), effluent IL-3 (p = 0.02; OR, 1.75; 95%
      CI, 1.2-2.9), and effluent IL-13 (p = 0.006; OR, 0.67; 95% CI, 0.50-0.87) were
      independently associated with HO formation. Injury Severity Score (p = 0.05; OR,
      18; 95% CI, 5.1-87), wound surface area (p = 0.05; OR, 28.7; 95% CI, 1.5-1250),
      serum procalcitonin ([ProCT] (p = 0.03; OR, 1596; 95% CI, 5.1-1,758,613) and
      effluent IL-6 (p = 0.02; OR, 83; 95% CI, 2.5-5820) were independently associated
      with wound failure. CONCLUSIONS: We identified associations between patients'
      systemic and local inflammatory responses and wound-specific complications such
      as HO and wound failure. However, future efforts to model these data must account
      for their complex, time dependent, and nonlinear nature. LEVEL OF EVIDENCE: Level
      II, prognostic study. See the Instructions for Authors for a complete description
      of levels of evidence.

PMID- 24879570
TI  - Community mental health in Italy today.

PMID- 24879569
TI  - Implant survival, adverse events, and bone remodeling of osseointegrated
      percutaneous implants for transhumeral amputees.
AB  - BACKGROUND: Osseointegrated percutaneous implants provide direct anchorage of the
      limb prosthesis to the residual limb. These implants have been used for the
      rehabilitation of transhumeral amputees in Sweden since 1995 using a two-stage
      surgical approach with a 6-month interval between the stages, but results on
      implant survival, adverse events, and radiologic signs of osseointegration and
      adaptive bone remodeling in transhumeral amputees treated with this method are
      still lacking. QUESTIONS/PURPOSES: This study reports on 2- and 5-year implant
      survival, adverse events, and radiologic signs of osseointegration and bone
      remodeling in transhumeral amputees treated with osseointegrated prostheses.
      METHODS: Between 1995 and 2010, we performed 18 primary osseointegrated
      percutaneous implants and two implant revisions in 18 transhumeral amputees; of
      those, 16 patients were available for followup at a minimum of 2 years (median, 8
      years; range, 2-19 years). These include all transhumeral amputees who have
      received osseointegrated prostheses and represented approximately 20% of the all
      transhumeral amputees we evaluated for potential osseointegration during that
      time; general indications for this approach included transhumeral amputation
      resulting from trauma or tumor, inability to wear or severe problems wearing a
      conventional socket prosthesis, eg, very short residual limb, and compliant
      patients. Medical charts and plain radiographs were retrospectively evaluated.
      RESULTS: The 2- and 5-year implant survival rates were 83% and 80%, respectively.
      Two primary and one revised implant failed and were removed because of early
      loosening. A fourth implant was partially removed because of ipsilateral shoulder
      osteoarthritis and subsequent arthrodesis. The most common adverse event was
      superficial infection of the skin penetration site (15 infections in five
      patients) followed by skin reactions of the skin penetration site (eight),
      incomplete fracture at the first surgery (eight), defective bony canal at the
      second surgery (three), avascular skin flap necrosis (three), and one deep
      implant infection. The most common radiologic finding was proximal trabecular
      buttressing (10 of 20 implants) followed by endosteal bone resorption and
      cancellization (seven of 20), cortical thinning (five of 20), and distal bone
      resorption (three of 20). CONCLUSIONS: The implant system presented a
      survivorship of 83% at 5 years and a 38% 5-year incidence of infectious
      complications related to the skin penetration site that were easily managed with
      nonoperative treatment, which make it a potentially attractive alternative to
      conventional socket arm prostheses. Osseointegrated arm prostheses have so far
      only been used in transhumeral amputations resulting from either trauma or tumor.
      Their use has not been tested and is therefore not recommended in transhumeral
      amputations resulting from vascular disease. This method could theoretically be
      superior to socket prostheses, especially in transhumeral amputees with very
      short residual humerus in which the suspension of a conventional prosthesis is
      difficult. Comparative studies are needed to support its potential superiority.
      Moreover, the radiological findings in this study need to be followed over time
      because some of them are of uncertain long-term clinical relevance.

PMID- 24879571
TI  - Monitoring and evaluating the Italian mental health system: the "Progetto
      Residenze" study and beyond.
AB  - Filling an alarming gap in evidence-based data on the post-1978 reformed Italian
      psychiatric system, two turn-of-millennium nationwide projects, Progetto
      Residenze (PROGRES) and PROGRES-Acute, provided detailed qualitative-quantitative
      information about care facilities. In 2000, there were 2.9 residential beds per
      10,000 inhabitants, hospital care being delivered through small (15-bed)
      psychiatric units. Private inpatient facilities had proliferated, private
      inpatient beds per 10,000 inhabitants outnumbering public beds. In 2002, there
      were 1.7 acute inpatient beds per 10,000 inhabitants, one of Europe's lowest
      current ratios. The PROGRES and other subsequent projects showed marked
      nationwide variation in the provision of residential inpatient and outpatient
      care, grounds for concern about the quality of such care, and an uneven service
      use pattern. Although the Italian reform law produced a broad network of
      facilities to meet diverse mental health care needs, the present overview article
      confirms that further efforts are required to improve quality, balance public and
      private sectors, and coordinate resources and agencies. 

PMID- 24879572
TI  - Italian families and family interventions.
AB  - In Italy, as in many countries, relatives are closely involved in caring for
      persons with physical and mental disorders. The Italian scenario lends itself to
      routine involvement of family members in psychiatric treatment because, despite
      becoming smaller and smaller, Italian families keep close ties, and men and women
      do not leave the parental home until relatively late. The authors describe the
      impact of international family psychosocial research on the Italian mental health
      services (MHSs) and the main psychosocial interventions currently in use,
      including family psychoeducational interventions and the "Milan family therapy
      approach." They also highlight the contribution Italian researchers have given to
      the study of important variables in integrated mental disorder care, such as
      family burden of care, relatives' attitudes, family functioning, and satisfaction
      with the MHSs. Finally, they discuss the difficulties of implementing and
      disseminating family interventions within the Italian MHS, despite the growing
      evidence of their effectiveness. 

PMID- 24879573
TI  - Endotoxins affect diverse biological activity of chitosans in matters of
      hemocompatibility and cytocompatibility.
AB  - Chitosan is used in several pharmaceutical and medical applications, owing to its
      good cytocompatibility and hemocompatibility. However, there are conflicting
      reports regarding the biological activities of chitosan with some studies
      reporting anti-inflammatory properties while others report pro-inflammatory
      properties. In this regards we analyzed the endotoxin content in five different
      chitosans and examined these chitosans with their different deacetylation degrees
      for their hemocompatibility and cytocompatibility. Therefore, we incubated
      primary human endothelial cells or whole blood with different chitosan
      concentrations and studied the protein and mRNA expression of different
      inflammatory markers or cytokines. Our data indicate a correlation of the
      endotoxin content and cytokine up-regulation in whole blood for Poly-Morpho
      Nuclear (PMN)-Elastase, soluble terminal complement complex SC5b-9, complement
      component C5/C5a, granulocyte colony-stimulating factor, Interleukin-8 (IL), IL
      10, IL-13, IL-17E, Il-32alpha and monocyte chemotactic protein-1. In contrast,
      the incubation of low endotoxin containing chitosans with primary endothelial
      cells resulted in increased expression of E-selectin, intercellular adhesion
      molecule-1, vascular cell adhesion protein-1, IL-1beta, IL-6 and IL-8 in
      endothelial cells. We suggest that the endotoxin content in chitosan plays a
      major role in the biological activity of chitosan. Therefore, we strongly
      recommend analysis of the endotoxin concentration in chitosan, before further
      determining if it has pro- or anti-inflammatory properties or if it is applicable
      for pharmaceutical and medical fields. 

PMID- 24879574
TI  - In vitro DNA binding, pBR322 plasmid cleavage and molecular modeling study of
      chiral benzothiazole Schiff-base-valine Cu(II) and Zn(II) complexes to evaluate
      their enantiomeric biological disposition for molecular target DNA.
AB  - Bicyclic heterocyclic compounds viz. benzothiazoles are key components of
      deoxyribonucleic acid (DNA) molecules and participate directly in the encoding of
      genetic information. Benzothiazoles, therefore, represent a potent and selective
      class of antitumor compounds. The design and synthesis of chiral antitumor
      chemotherapeutic agents of Cu(II) and Zn(II), L- and -D benzothiazole Schiff base
      valine complexes 1a &b and 2a &b, respectively were carried out and thoroughly
      characterized by spectroscopic and analytical techniques. Interaction of 1a and b
      and 2a and b with CT DNA by employing UV-vis, florescence, circular dichroic
      methods and cleavage studies of 1a with pBR322 plasmid, molecular docking were
      done in order to demonstrate their enantiomeric disposition toward the molecular
      drug target DNA. Interestingly, these studies unambiguously demonstrated the
      greater potency of L-enantiomer in comparison to D-enantiomer. 

PMID- 24879577
TI  - The role of Bi vacancies in the electrical conduction of BiFeO3: a first
      principles approach.
AB  - We employ first-principles methods to study the mechanism controlling the
      electrical conduction in BiFeO3 (BFO). We find that under oxygen-rich conditions,
      Bi vacancies (V(Bi)) have lower defect formation energy than O vacancies (V(O)) (
      0.43 eV vs. 3.35 eV), suggesting that V(Bi) are the acceptor defects and control
      the conductivity of BFO, making it a p-type semiconductor. In order to obtain
      further insight into the conduction mechanism, we calculate the effect of donor
      (Sn(4+)) and acceptor (Pb(2+)) impurities in BFO. Results indicate that Sn
      impurities prefer to substitute Fe sites to form shallow donor defects, which
      compensate the acceptor levels derived from V(Bi). Meanwhile, Pb atoms favour the
      substitution of Bi sites to form acceptor defects, reducing the overall
      concentration of holes (h(+)). Theoretical findings were later surveyed by
      current-voltage characteristics of Sn- or Pb-doped BFO nanofibers. This study is
      of general interest in carrier transport in charge compensation semiconductors,
      and of particular relevance within the context of defect-mediated conductivity in
      BFO.

PMID- 24879576
TI  - Missing Concepts in De Novo Pulp Regeneration.
AB  - Regenerative endodontics has gained much attention in the past decade because it
      offers an alternative approach in treating endodontically involved teeth. Instead
      of filling the canal space with artificial materials, it attempts to fill the
      canal with vital tissues. The objective of regeneration is to regain the tissue
      and restore its function to the original state. In terms of pulp regeneration, a
      clinical protocol that intends to reestablish pulp/dentin tissues in the canal
      space has been developed--termed revitalization or revascularization. Histologic
      studies from animal and human teeth receiving revitalization have shown that pulp
      regeneration is difficult to achieve. In tissue engineering, there are 2
      approaches to regeneration tissues: cell based and cell free. The former involves
      transplanting exogenous cells into the host, and the latter does not.
      Revitalization belongs to the latter approach. A number of crucial concepts have
      not been well discussed, noted, or understood in the field of regenerative
      endodontics in terms of pulp/dentin regeneration: (1) critical size defect of
      dentin and pulp, (2) cell lineage commitment to odontoblasts, (3) regeneration
      vs. repair, and (4) hurdles of cell-based pulp regeneration for clinical
      applications. This review article elaborates on these missing concepts and
      analyzes them at their cellular and molecular levels, which will in part explain
      why the non-cell-based revitalization procedure is difficult to establish
      pulp/dentin regeneration. Although the cell-based approach has been proven to
      regenerate pulp/dentin, such an approach will face barriers--with the key hurdle
      being the shortage of the current good manufacturing practice facilities,
      discussed herein.

PMID- 24879575
TI  - Utility of salivary biomarkers for demonstrating acute myocardial infarction.
AB  - The comparative utility of serum and saliva as diagnostic fluids for identifying
      biomarkers of acute myocardial infarction (AMI) was investigated. The goal was to
      determine if salivary biomarkers could facilitate a screening diagnosis of AMI,
      especially in cases of non-ST elevation MI (NSTEMI), since these cases are not
      readily identified by electrocardiogram (ECG). Serum and unstimulated whole
      saliva (UWS) collected from 92 AMI patients within 48 hours of chest pain onset
      and 105 asymptomatic healthy control individuals were assayed for 13 proteins
      relevant to cardiovascular disease, by Beadlyte technology (Luminex((r))) and
      enzyme immunoassays. Data were analyzed with concentration cut-points, ECG
      findings, logistic regression (LR) (adjusted for matching for age, gender, race,
      smoking, number of teeth, and oral health status), and classification and
      regression tree (CART) analysis. A sensitivity analysis was conducted by
      repetition of the CART analysis in 58 cases and 58 controls, each matched by age
      and gender. Serum biomarkers demonstrated AMI sensitivity and specificity
      superior to that of saliva, as determined by LR and CART. The predominant
      discriminators in serum by LR were troponin I (TnI), B-type natriuretic peptide
      (BNP), and creatine kinase-MB (CK-MB), and TnI and BNP by CART. In saliva, LR
      identified C-reactive protein (CRP) as the biomarker most predictive of AMI. A
      combination of smoking tobacco, UWS CRP, CK-MB, sCD40 ligand, gender, and number
      of teeth identified AMI in the CART decision trees. When ECG findings, salivary
      biomarkers, and confounders were included, AMI was predicted with 80.0%
      sensitivity and 100% specificity. These analyses support the potential utility of
      salivary biomarker measurements used with ECG for the identification of AMI.
      Thus, saliva-based tests may provide additional diagnostic screening information
      in the clinical course for patients suspected of having an AMI. 

PMID- 24879578
TI  - Regulation of pharmaceutical prices: evidence from a reference price reform in
      Denmark.
AB  - Reference price systems for prescription drugs constitute widely adopted cost
      containment tools. Under these regimes, patients co-pay a fraction of the
      difference between a drug's pharmacy retail price and a reference price that is
      set by the government. Reference prices are either externally (based on drug
      prices in other countries) or internally (based on domestic drug prices)
      determined. We study the effects of a change from external to internal reference
      pricing in Denmark in 2005. We find that the reform led to substantial reductions
      in retail prices, reference prices and patient co-payments as well as to sizable
      decreases in overall producer revenues and health care expenditures. The reform
      induced consumers to substitute away from branded drugs for which we estimate
      strong preferences. The increase in consumer welfare due to the reform therefore
      depends on whether or not we take perceived quality differences into account in
      its calculation. 

PMID- 24879580
TI  - Pathology-based approach to epilepsy surgery.

PMID- 24879579
TI  - Improved health-related quality of life outcomes associated with SHH subgroup
      medulloblastoma in SIOP-UKCCSG PNET3 trial survivors.

PMID- 24879581
TI  - Comparing the process of creeping substitution between allograft bone and local
      bone grafting in lumbar interbody fusion.
AB  - PURPOSE: A self-control study was designed to compare the process of creeping
      substitution between allograft bone and local bone grafting in lumbar interbody
      fusion. METHODS: From December 2011 to July 2012, 81 patients (mean age: 56.4)
      were included in this study and randomly allocated to two groups. Leopard cages
      were using in unilateral instrumentation transforaminal lumbar interbody fusion.
      In group 1, the cages were filled with the local bone on the side of the
      instrumentation and allograft bone on the other side. In group 2, they were
      totally filled with the local bone chips. Then, the special CT-reconstructions
      were made at 6- and 12-month follow-up. On the sagittal section, the sections of
      CT-reconstructions were perpendicular to the lateral axis of the cage from the
      side of the cage to the other side. Similarly, they were parallel to the lateral
      axis of the cage on the coronal section and intervertebral space on the cross
      section. The mean area size of bone mass on both sides of the cage was
      calculated, respectively, using image analysis software (Osirix, version 3.3.2)
      on each section in two groups. RESULTS: In group 1, at 6- and 12-month follow-up,
      significant differences were observed in the mean area size of bone mass between
      allograft bone and local bone grafting on the coronal, cross, and sagittal
      section. In group 2, the mean area size of local bone on both sides of the cage
      had no significant differences at 6- and 12-month follow-up on each section.
      CONCLUSIONS: The results of our study showed a superiority of local bone grafting
      over allograft bone.

PMID- 24879582
TI  - Effect of high pressure microfluidization on the crystallization behavior of palm
      stearin - palm olein blends.
AB  - Moderate and high microfluidization pressures (60 and 120 MPa) and different
      treatment times (once and twice) were used to investigate the effect of high
      pressure microfluidization (HPM) treatment on the crystallization behavior and
      physical properties of binary mixtures of palm stearin (PS) and palm olein (PO).
      The polarized light microscopy (PLM), texture analyzer, X-ray diffraction (XRD)
      and differential scanning calorimetry (DSC) techniques were applied to analyze
      the changes in crystal network structure, hardness, polymorphism and thermal
      property of the control and treated blends. PLM results showed that HPM caused
      significant reductions in maximum crystal diameter in all treated blends, and
      thus led to changes in the crystal network structure, and finally caused higher
      hardness in than the control blends. The XRD study demonstrated that HPM altered
      crystalline polymorphism. The HPM-treated blends showed a predominance of the
      more stable beta' form, which is of more interest for food applications, while
      the control blend had more alpha- and beta-form. This result was further
      confirmed by DSC observations. These changes in crystallization behavior
      indicated that HPM treatment was more likely to modify the crystallization
      processes and nucleation mechanisms. 

PMID- 24879583
TI  - Antioxidant and antiproliferative activities of methanolic extract from a
      neglected agricultural product: corn cobs.
AB  - Neglected agricultural products (NAPs) are defined as discarded material in
      agricultural production. Corn cobs are a major waste of agriculture maize. Here,
      a methanolic extract from corn cobs (MEC) was obtained. MEC contains phenolic
      compounds, protein, carbohydrates (1.4:0.001:0.001). We evaluated the in vitro
      and in vivo antioxidant potential of MEC. Furthermore, its antiproliferative
      property against tumor cells was assessed through MTT assays and proteins related
      to apoptosis in tumor cells were examined by western blot. MEC showed no hydroxyl
      radical scavenger capacity, but it showed antioxidant activity in Total
      Antioxidant Capacity and DPPH scavenger ability assays. MEC showed higher
      Reducing Power than ascorbic acid and exhibited high Superoxide Scavenging
      activity. In tumor cell culture, MEC increased catalase, metallothionein and
      superoxide dismutase expression in accordance with the antioxidant tests. In vivo
      antioxidant test, MEC restored SOD and CAT, decreased malondialdehyde activities
      and showed high Trolox Equivalent Antioxidant Capacity in animals treated with
      CCl4. Furthermore, MEC decreased HeLa cells viability by apoptosis due an
      increase of Bax/Bcl-2 ratio, caspase 3 active. Protein kinase C expression
      increased was also detected in treated tumor cells. Thus, our findings pointed
      out the biotechnological potential of corn cobs as a source of molecules with
      pharmacological activity. 

PMID- 24879584
TI  - Role of microRNA in response to ionizing radiations: evidences and potential
      impact on clinical practice for radiotherapy.
AB  - MicroRNAs (miRNA) are small, non-coding, RNAs with gene expression regulator
      roles. As an important class of regulators of many cellular pathways, miRNAs are
      involved in many signaling pathways and DNA damage repair processes, affecting
      cellular radiosensitivity. Their role has led to interest in oncological
      implications to improve treatment results. MiRNAs represent a great opportunity
      to enhance the efficacy of radiotherapy treatments-they can be used to profile
      the radioresistance of tumors before radiotherapy, monitor their response
      throughout the treatment, thus helping to select intensification strategies, and
      also to define the final response to therapy along with risks of recurrence or
      metastatization. Even though many interesting studies support such potential,
      nowadays most studies on patient data are limited to experiments profiling tumor
      aggressiveness and response to radiotherapy. Moreover many studies report
      different although not conflicting results on the miRNAs evaluated for each tumor
      type. Without doubt, the clinical potential of such molecules for radiotherapy is
      striking and of high interest. 

PMID- 24879585
TI  - In vitro studies of the activity of dithiocarbamate organoruthenium complexes
      against clinically relevant fungal pathogens.
AB  - The in vitro antifungal activity of nine dirutheniumpentadithiocarbamate
      complexes C1-C9 was investigated and assessed for its activity against four
      different fungal species with clinical interest and related to invasive fungal
      infections (IFIs), such as Candida spp. [C. albicans (two clinical isolates), C.
      glabrata, C. krusei, C. parapsolisis, C. tropicalis, C.dubliniensis (six clinical
      isolates)], Paracoccidioides brasiliensis (seven clinical isolates), Cryptococcus
      neoformans and Sporothrix schenckii. All synthesized complexes C1-C9 and also the
      free ligands L1-L9 were submitted to in vitro tests against those fungi and the
      results are very promising, since some of the obtained MIC (minimal inhibitory
      concentration) values were very low (from 10-6 mol mL-1 to 10-8 mol mL-1) against
      all investigated clinically relevant fungal pathogens, except for C. glabrata,
      that the MIC values are close to the ones obtained for fluconazole, the standard
      antifungal agent tested. Preliminary structure-activity relations (SAR) might be
      suggested and a strong influence from steric and lipophilic parameters in the
      antifungal activity can be noticed. Cytotoxicity assays (IC50) showed that the
      complexes are not as toxic (IC50 values are much higher-30 to 200 fold-than MIC
      values). These ruthenium complexes are very promising lead compounds for novel
      antifungal drug development, especially in IFIs, one of most harmful emerging
      infection diseases (EIDs). 

PMID- 24879586
TI  - Conformational characterization of ipomotaosides and their recognition by COX-1
      and 2.
AB  - The aerial parts of Ipomoea batatas are described herein to produce four new
      resin glycosides, designated as ipomotaosides A, B, C, and D. Ipomotaoside A was
      found to present inhibitory activity on both cyclooxygenases. However, the
      conformational elucidation of these molecules may be difficult due to their high
      flexibility. In this context, the current work presents a conformational
      characterization of ipomotaosides A-D in aqueous and nonaqueous solvents. The
      employed protocol includes metadynamics evaluation and unrestrained molecular
      dynamics simulations (MD). The obtained data provided structural models for the
      ipomotaosides in good agreement with previous ROESY distances measured in
      pyridine. Accordingly, the most abundant conformation of ipomotaoside A in
      solution was employed in flexible docking studies, providing a structural basis
      for the compound's inhibition of COX enzymes. The so-obtained complex supports
      resin glycosides' role as original scaffolds for future studies, aiming at
      structural optimization and development of potential new anti-inflammatory
      agents. 

PMID- 24879587
TI  - Quantification, antioxidant and antimicrobial activity of phenolics isolated from
      different extracts of Capsicum frutescens (Pimenta Malagueta).
AB  - This paper presents the quantification, antioxidant and antimicrobial activity of
      capsaicin, dihydrocapsaicin and the flavonoid chrysoeriol isolated from different
      extracts (hexane and acetonitrile extracts from whole fruit, peel and seed) of
      Capsicum frutescens (pimenta malagueta). The acetonitrile extract of the seeds,
      peel and whole fruits contained capsaicin as a major component, followed in
      abundance by dihydrocapsaicin and chrysoeriol. The antimicrobial activity of the
      isolated compounds against seven microorganisms showed chrysoeriol was the most
      active compound. In the antioxidant test, the acetonitrile extract from the whole
      fruit showed the highest activity. The antioxidant activity of pimenta malagueta
      may be correlated with its phenolic content, principally with the most active
      compound, capsaicin. 

PMID- 24879588
TI  - Two ellagic acids isolated from roots of Sanguisorba officinalis L. promote
      hematopoietic progenitor cell proliferation and megakaryocyte differentiation.
AB  - Using a bioassay-directed chromatographic separation, two ellagic acids were
      obtained from the ethyl acetate extract of the roots of Sanguisorba officinalis
      L. On the basis of chemical and spectroscopic methods, the two ellagic acids were
      identified as 3,3',4-tri-O-methylellagic acid-4'-O-beta-d-xyloside and 3,3',4-tri
      O-methylellagic acid. Stimulation of cell proliferation was assayed in
      hematopoietic progenitor cells using the Cell Counting kit-8 method. The
      megakaryocyte differentiation was determined in human erythroleukemia (HEL) cells
      using Giemsa staining and flow cytometry analysis. The ellagic acids
      significantly stimulated the proliferation of Baf3/Mpl cells. Morphology analysis
      and megakaryocyte specific-marker CD41 staining confirmed that the ellagic acids
      induced megakaryocyte differentiation in HEL cells. This is the first time that
      3,3',4-tri-O-methylellagic acid or 3,3',4-tri-O-methylellagic acid-4'-O-beta-d
      xyloside are reported to induce megakaryopoiesis, suggesting a class of small
      molecules which differ from others non-peptidyl, and appears to have potential
      for clinical development as a therapeutic agent for patients with blood platelet
      disorders. 

PMID- 24879589
TI  - Long-term survival after pancreatic resection for renal cell carcinoma
      metastasis.
AB  - BACKGROUND: Surgical resection of pancreatic metastasis (PM) is the only reported
      curative treatment for renal cell carcinoma. However, there is currently little
      information regarding very long-term survival. The primary objective of this
      study was to determine the 10-year survival of this condition using the largest
      surgical series reported to date. METHODS: Between May 1987 and June 2003, we
      conducted a retrospective study of 62 patients surgically treated for PM from
      renal cell carcinoma at 12 Franco-Belgian surgical centers. Follow-up ended on
      May 31, 2012. RESULTS: There were 27 male (44 %) and 35 female (56 %) patients
      with a median age of 54 years [31-75]. Mean disease-free interval from resection
      of primary tumor to reoperation for pancreatic recurrence was 9.8 years (median
      10 years [0-25]). During a median follow-up of 91 months [12-250], 37 recurrences
      (60 %) were observed. After surgical resection of repeated recurrences, overall
      median survival time was 52.6 months versus 11.2 months after nonoperative
      management (p = 0.019). Cumulative 3-, 5-, and 10-year overall survival (OS)
      rates were 72, 63, and 32 %, respectively. The corresponding disease-free
      survival rates were 54, 35, and 27 %, respectively. Lymph node involvement and
      existence of extrapancreatic metastases before PM were associated with poor
      overall survival. CONCLUSIONS: Aggressive surgical management of single or
      multiple PM, even in cases of extrapancreatic disease, should be considered in
      selected patients to allow a chance of long-term survival.

PMID- 24879590
TI  - LKB1 loss at transcriptional level promotes tumor malignancy and poor patient
      outcomes in colorectal cancer.
AB  - BACKGROUND: Liver kinase B1 (LKB1) loss by gene mutation, loss of heterozygosity,
      and promoter methylation rarely occurs in colorectal cancer. We wondered whether
      LKB1 loss could be deregulated at the transcriptional level to promote tumor
      progression and poor outcome in colorectal cancer. METHODS: Mechanistic studies
      were performed in two each of p53 wild-type (HCT116, LoVo) and p53-mutated
      (SW480, HT29) colon cancer cells to explore whether LKB1 loss could be
      deregulated by NKX2-1-mediated p53 pathway. LKB1 and NK2 homeobox 1 (NKX2-1)
      expressions in colorectal tumors were determined by immunohistochemistry, and the
      prognostic value of both molecules was assessed by Kaplan-Meier test and Cox
      regression model. RESULTS: Mechanistically, LKB1 loss at the transcriptional
      level due to alteration of the NKX2-1-mediated p53 pathway promotes invasiveness
      in colon cancer cells. The cell invasiveness induced by LKB1 loss was nearly
      suppressed by mammalian target of rapamycin (mTOR) inhibitor (rapamycin and
      everolimus) and mTOR/AKT dual inhibitor Palomid 529 (P529). Among patients, low
      LKB1 tumors exhibited shorter overall survival (OS) and relapse-free survival
      periods than high LKB1 tumors. The highest hazard ratio value for OS and relapse
      free survival was observed in wild-type p53 with low LKB1/low NKX2-1 tumors and
      in mutated p53 with low LKB1/high NKX2-1 tumors when wild-type p53 with high
      LKB1/high NKX2-1 and mutated p53 with high LKB1/low NKX2-1 tumors were used as
      references. CONCLUSIONS: LKB1 loss at the transcriptional level via alteration of
      the NKX2-1/p53 axis promotes cell invasion, consequently resulting in poor
      outcome in colorectal cancer patients.

PMID- 24879591
TI  - Ultrasensitive electrochemical immunosensor based on Pt nanoparticle-graphene
      composite.
AB  - We report a protein antibody, Ab-CRP, functionalized Pt nanoparticle-decorated
      chemical vapor deposition (CVD)-grown graphene on glassy carbon electrode, as a
      bioelectrode, for the quantitative analysis of human C-reactive protein (CRP).
      Chemical vapor deposition was used to grow a polycrystalline graphene film on
      copper and was mounted over a glassy carbon electrode after copper etching
      through pi-pi stacking. Ab-CRP was covalently immobilized on mercaptopropionic
      acid (MPA)-capped Pt nanoparticles that were covalently anchored over the
      graphene to form a bioelectrode. The bioelectrode was characterized by scanning
      electron microscopy, cyclic voltammetry, and electrochemical impedance
      spectroscopy (EIS). A detail EIS study was conducted on the bioelectrode towards
      the quantitative detection of the target Ag-CRP in phosphate-buffered saline
      (PBS). The optimal electrical equivalent circuit that matches the impedance
      response of the bioelectrode was studied to delineate the biocompatibility,
      sensitivity, and selectivity of the bioelectrode. The bioelectrode exhibited a
      linear response of CRP detection in the range of 10 ng mL(-1) to 10 MUg mL(-1)
      with a sensitivity of 92.86 Omegacm(2) per decade CRP in pH 7.4 PBS. 

PMID- 24879592
TI  - Production and characterization of a novel thermostable extracellular agarase
      from Pseudoalteromonas hodoensis newly isolated from the West Sea of South Korea.
AB  - A Gram-negative, aerobic, motile, rod-shaped, agarolytic bacterium, designated as
      H7, was isolated from a coastal seawater sample. This strain grows at pH 6.0-8.0,
      temperature of 15-40  degrees C, and at an NaCl concentration of 1-7% (w/v).
      Ubiquinone-8 was the predominant respiratory quinone, and the DNA G+C content was
      45.82 mol%. Analysis of the 16S rRNA sequence suggests that strain H7 belongs to
      the genus Pseudoalteromonas. DNA-DNA hybridization analysis showed DNA
      relatedness of as low as 55.42 and 40.27% with its nearest phylogenetic neighbors
      Pseudoalteromonas atlantica IAM12927T and Pseudoalteromonas espejiana NCIMB2127T,
      respectively, which led us to name H7 Pseudoalteromonas hodoensis sp. nov. The
      type strain is H7T (=DSM25967T=KCTC23887T). An agarase (AgaA7) was purified to
      homogeneity from the cell-free culture broth of H7 through many steps of
      chromatography. Purified AgaA7 had an apparent molecular weight of 35 kDa, with a
      distinct NH2-terminal sequence of Ala-Asp-Ala-Thr-X-Pro (X, any amino acid) from
      the reported proteins, implying that it is a novel enzyme. The optimum pH and
      temperature for agarase activity were 7.0 and 45  degrees C, respectively. Thin
      layer chromatography analysis, mass spectrometry, and enzyme assay using p
      nitrophenyl-alpha/beta-D-galactopyranoside revealed that AgaA7 is both an exo-
      and endo-type beta-agarase that degrades agarose into neoagarotetraose,
      neoagarohexaose, and neoagarooctaose (minor).

PMID- 24879593
TI  - Controlled continuous bio-hydrogen production using different biogas release
      strategies.
AB  - Dark fermentation for bio-hydrogen (bio-H2) production is an easily operated and
      environmentally friendly technology. However, low bio-H2 production yield has
      been reported as its main drawback. Two strategies have been followed in the past
      to improve this fact: genetic modifications and adjusting the reaction
      conditions. In this paper, the second one is followed to regulate the bio-H2
      release from the reactor. This operating condition alters the metabolic pathways
      and increased the bio-H2 production twice. Gas release was forced in the
      continuous culture to study the equilibrium in the mass transfer between the
      gaseous and liquid phases. This equilibrium depends on the H2, CO2, and volatile
      fatty acids production. The effect of reducing the bio-H2 partial pressure (bio
      H2 pp) to enhance bio-H2 production was evaluated in a 30 L continuous stirred
      tank reactor. Three bio-H2 release strategies were followed: uncontrolled,
      intermittent, and constant. In the so called uncontrolled fermentation, without
      bio-H2 pp control, a bio-H2 molar yield of 1.2 mol/mol glucose was obtained. A
      sustained low bio-H2 pp of 0.06 atm increased the bio-H2 production rate from
      16.1 to 108 mL/L/h with a stable bio-H2 percentage of 55% (v/v) and a molar yield
      of 1.9 mol/mol glucose. Biogas release enhanced bio-H2 production because lower
      bio-H2 pp, CO2 concentration, and reduced volatile fatty acids accumulation
      prevented the associated inhibitions and bio-H2 consumption.

PMID- 24879594
TI  - Over-expression of a proline specific aminopeptidase from Aspergillus oryzae JN
      412 and its application in collagen degradation.
AB  - A strain that exhibited intracellular proline-specific aminopeptidase (PAP)
      activity was isolated from soy sauce koji and identified as Aspergillus oryzae JN
      412. The gene coding PAP was cloned and efficiently expressed in Escherichia coli
      BL21 in a biologically active form. The highest specific activity reached 52.28 U
      mg(-1) at optimum cultivation conditions. The recombinant enzyme was purified 3.3
      fold to homogeneity with a recovery of 36.7% from cell-free extract using Ni
      affinity column chromatography. It appeared as a single protein band on SDS-PAGE
      with molecular mass of approximately 50 kDa. The purified enzyme exhibited the
      highest activity at 60  degrees C and pH 7.5. The enzyme activity was inhibited
      by PMSF and ions like Zn2+ and Cu2+. DTT, beta-mercaptoethanol, EDTA, and ions
      like Co2+, Mg2+, Mn2+, and Ca2+ had no influence on enzyme activity, whereas Ni2+
      enhanced the enzyme activity. By using collagen as a substrate, the purified
      recombinant prolyl aminopeptidase contributed to the hydrolysis of collagen when
      used in combination with neutral protease, and free amino acids in collagen
      hydrolysates was significantly increased.

PMID- 24879595
TI  - Immobilized lipase from Candida sp. 99-125 on hydrophobic silicate:
      characterization and applications.
AB  - Lipase Candida sp. 99-125 has been proved to be quite effective in catalyzing
      organic synthesis reactions and is much cheaper than commercial lipases.
      Mesoporous silicates are attractive materials for the immobilization of enzymes
      due to their unique structures. The present research designed a hydrophobic
      silicate with uniform pore size suitable for the comfort of lipase Candida sp. 99
      125 for improving its activity and stability. The resulting immobilized lipase
      (LP@PMO) by adsorption was employed to catalyze hydrolysis, esterification, and
      transesterification reactions, and the performances were compared with the lipase
      immobilized on hydrophilic silicate (LP@PMS) and native lipase. The LP@PMO showed
      as high activity as that of native lipase in hydrolysis and much increased
      catalytic activity and reusability in the reactions for biodiesel production.
      Besides, LP@PMO also possessed better organic stability. Such results demonstrate
      that immobilization of lipase onto hydrophobic supports is a promising strategy
      to fabricate highly active and stable biocatalysts for applications. 

PMID- 24879596
TI  - Purification of peroxidase from red cabbage (Brassica oleracea var. capitata f.
      rubra) by affinity chromatography.
AB  - Peroxidase was purified in a single step using 4-amino benzohydrazide affinity
      chromatography from red cabbage (Brassica oleracea var. capitata f. rubra), and
      some important biochemical characteristics of the purified enzyme were
      determined. The enzyme, with a specific activity of 3,550 EU/mg protein, was
      purified 120.6-fold with a yield of 2.9% from the synthesized affinity matrix.
      The molecular weight of the enzyme was found to be 69.3 kDa by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The enzyme exhibited
      maximum activity at pH 7.0 and 30  degrees C. For guaiacol substrate, the K m and
      V max values were found as 0.048 mM and 1.46 EU/mL/min, respectively.
      Additionally, the IC50 and K i values for 4-amino benzohydrazide were calculated
      to be 1.047 and 0.702+/-0.05 mM, respectively, and 4-amino benzohydrazide showed
      noncompetitive inhibition.

PMID- 24879597
TI  - Phytase production by Aspergillus oryzae in solid-state fermentation and its
      applicability in dephytinization of wheat bran [corrected].
AB  - Aspergillus oryzae SBS50 secreted a high titre of phytase in solid-state
      fermentation (SSF) using wheat bran at 30  degrees C after 96 h at the initial
      substrate to moisture ratio of 1:2 and a water activity of 0.95. The production
      of phytase increased when wheat bran was supplemented with sucrose and beef
      extract. Further enhancement in enzyme production was recorded when the substrate
      was supplemented with the surfactant Triton X-100 (145 U/g of DMB). An overall 29
      fold improvement in phytase production was achieved owing to optimization. Under
      optimized conditions, the mould secreted 9.3-fold higher phytase in SSF as
      compared to submerged fermentation (SmF). The mesophilic mould also secreted
      amylase, cellulase (CMCase), pectinase and xylanase along with phytase in SSF.
      Scanning electron microscopy revealed luxuriant growth of A. oryzae on wheat bran
      with abundant spores. The enzyme dephytinized wheat bran with concomitant
      liberation of inorganic phosphate. 

PMID- 24879598
TI  - Enhanced L-lactic acid production from biomass-derived xylose by a mutant
      Bacillus coagulans.
AB  - Xylose effective utilization is crucial for production of bulk chemicals from low
      cost lignocellulosic substrates. In this study, an efficient L-lactate production
      process from xylose by a mutant Bacillus coagulans NL-CC-17 was demonstrated. The
      nutritional requirements for L-lactate production by B. coagulans NL-CC-17 were
      optimized statistically in shake flask fermentations. Corn steep liquor powder
      and yeast exact were identified as the most significant factors by the two-level
      Plackett-Burman design. Steepest ascent experiments were applied to approach the
      optimal region of the two factors, and a central composite design was employed to
      determine their optimal levels. The optimal medium was used to perform batch
      fermentation in a 3-l bioreactor. A maximum of 90.29 g l(-1)  L-lactic acid was
      obtained from 100 g l(-1) xylose in 120 h. When using corn stove prehydrolysates
      as substrates, 23.49 g l(-1)  L-lactic acid was obtained in 36 h and the yield
      was 83.09 %. 

PMID- 24879599
TI  - Adaptive evolution of Saccharomyces cerevisiae with enhanced ethanol tolerance
      for Chinese rice wine fermentation.
AB  - High tolerance towards ethanol is a desirable property for the Saccharomyces
      cerevisiae strains used in the alcoholic beverage industry. To improve the
      ethanol tolerance of an industrial Chinese rice wine yeast, a sequential batch
      fermentation strategy was used to adaptively evolve a chemically mutagenized
      Chinese rice wine G85 strain. The high level of ethanol produced under Chinese
      rice wine-like fermentation conditions was used as the selective pressure. After
      adaptive evolution of approximately 200 generations, mutant G85X-8 was isolated
      and shown to have markedly increased ethanol tolerance. The evolved strain also
      showed higher osmotic and temperature tolerances than the parental strain.
      Laboratory Chinese rice wine fermentation showed that the evolved G85X-8 strain
      was able to catabolize sugars more completely than the parental G85 strain. A
      higher level of yeast cell activity was found in the fermentation mash produced
      by the evolved strain, but the aroma profiles were similar between the evolved
      and parental strains. The improved ethanol tolerance in the evolved strain might
      be ascribed to the altered fatty acids composition of the cell membrane and
      higher intracellular trehalose concentrations. These results suggest that
      adaptive evolution is an efficient approach for the non-recombinant modification
      of industrial yeast strains. 

PMID- 24879600
TI  - A diverse assemblage of indole-3-acetic acid producing bacteria associate with
      unicellular green algae.
AB  - Microalgae have tremendous potential as a renewable feedstock for the production
      of liquid transportation fuels. In natural waters, the importance of physical
      associations and biochemical interactions between microalgae and bacteria is
      generally well appreciated, but the significance of these interactions to algal
      biofuels production have not been investigated. Here, we provide a preliminary
      report on the frequency of co-occurrence between indole-3-acetic acid (IAA)
      producing bacteria and green algae in natural and engineered ecosystems. Growth
      experiments with unicellular algae, Chlorella and Scenedesmus, revealed IAA
      concentration-dependent responses in chlorophyll content and dry weight.
      Importantly, discrete concentrations of IAA resulted in cell culture
      synchronization, suggesting that biochemical priming of cellular metabolism could
      vastly improve the reliability of high density cultivation. Bacterial
      interactions may have an important influence on algal growth and development;
      thus, the preservation or engineered construction of the algal-bacterial assembly
      could serve as a control point for achieving low input, reliable production of
      algal biofuels. 

PMID- 24879601
TI  - Sensitive and reliable ascorbic acid sensing by lanthanum oxide/reduced graphene
      oxide nanocomposite.
AB  - A simple strategy for the detection and estimation of ascorbic acid (AA), using
      lanthanum oxide-reduced graphene oxide nanocomposite (LO/RGO) on indium tin oxide
      (ITO) substrate, is reported. LO/RGO displays high catalytic activity toward the
      oxidation of AA, and the synergism between lanthanum oxide and reduced graphene
      oxide was attributed to the successful and efficient detection. Detection
      mechanism and sensing efficacy of LO/RGO nanocomposite are investigated by
      electrochemical techniques. Chronoamperometric results under optimal conditions
      show a linear response range from 14 to 100 MUM for AA detection. Commercially
      available vitamin C tablets were also analyzed using the proposed LO/RGO sensor,
      and the remarkable recovery percentage (97.64-99.7) shows the potential
      application in AA detection. 

PMID- 24879602
TI  - Reexamination of the female sex pheromone of the sweet potato vine borer moth:
      identification and field evaluation of a tricosatriene.
AB  - The sweet potato vine borer moth, Omphisa anastomosalis (Pyraloidea: Crambidae),
      is a serious pest in tropical and subtropical Asia-Pacific regions. In previous
      work using a population from Okinawa, Japan, (10E,14E)-10,14-hexadecadienal
      (E10,E14-16:Ald) was identified as the major pheromone component, with
      hexadecanal, (E)-10-hexadecenal, and (E)-14-hexadecenal as minor components.
      However, traps baited with the synthetic compounds were less effective at
      attracting males in the field than those baited with virgin females. While
      Pyraloidea females usually produce only Type I pheromone components (unsaturated
      fatty alcohols and their derivatives), the pheromones of some Pyraloidea species
      have been shown to involve a combination of both Type I and Type II components
      (unsaturated hydrocarbons and their epoxides). We examined an extract of the
      pheromone glands of female O. anastomosalis from Vietnam by gas chromatography
      coupled to mass spectrometry and detected (3Z,6Z,9Z)-3,6,9-tricosatriene
      (Z3,Z6,Z9-23:H) in addition to the compounds identified previously. All four
      isomers of 10,14-16:Ald were synthesized. A mixture of synthetic E10,E14-16:Ald
      and Z3,Z6,Z9-23:H in a ratio of 1:0.2-1:2 was attractive to male moths in
      Vietnam, indicating the strong synergistic effect of the Type II compound.
      Addition of the other minor pheromone components to the binary blend did not
      increase the number of male moths captured. Combinations of Z3,Z6,Z9-23:H with
      the other three geometrical isomers of E10,E14-16:Ald attracted no males, further
      substantiating the 10E,14E configuration of the natural diene component. E10,E14
      16:Ald mixed with other polyunsaturated hydrocarbons showed that mixtures that
      included a C21 triene, a C22 triene, or a C23 pentaene attracted as many males as
      did the mixture with Z3,Z6,Z9-23:H. The identification of a highly attractive sex
      pheromone will help in developing efficient strategies for monitoring and control
      of O. anastomosalis populations in sweet potato fields. 

PMID- 24879603
TI  - Innate responses to putative ancestral hosts: is the attraction of Western flower
      thrips to pine pollen a result of relict olfactory receptors?
AB  - Pollinophagy is widely documented in the order Thysanoptera, with representative
      individuals from six of the nine divergent families known to feed on pollen.
      Various pollens of the genus Pinus increase the development time, fecundity,
      longevity, and settling preference of Western Flower Thrips (WFT), Frankliniella
      occidentalis (Pergande) (Thysanoptera: Thripidae). Certain species of flower
      thrips discriminate among pollen types, but no studies have elucidated the
      olfactory cues that play a role in their pollen preferences. In this study, the
      volatile organic compounds emitted by pollens of the genus Pinus were elucidated.
      Various chemicals from pollen headspace elicited electrophysiological responses
      from WFT antennae. The compound (S)-(-)-verbenone, identified in pollen
      headspace, attracted WFT in a 4-arm olfactometer. This compound has potential for
      use in integrated pest management programs against the pest. We present the
      hypothesis that this polyphagous insect may have retained ancestral 'relict'
      olfactory receptors through the course of evolution, to explain this attraction
      to pine pollen. This attraction has allowed the insect to find and exploit an
      unusual nutrient source that significantly increases its fitness. The study
      demonstrates how fossil record analysis and subsequent evolutionary knowledge can
      aid in explaining possibilities as to why some insects sense and respond to
      chemicals that would otherwise seem peculiar to their ecology, allowing insight
      into the evolutionary forces that may shape insect olfactory systems over time. 

PMID- 24879604
TI  - New synthesis: a holobiontic view on plant-insect interactions.

PMID- 24879605
TI  - Content validation of a tool for assessing risks for drug-related problems to be
      used by practical nurses caring for home-dwelling clients aged >=65 years: a
      Delphi survey.
AB  - PURPOSE: Home care services are becoming a critically important part of health
      care delivery as populations are aging. Those using home care services are
      increasingly older, more frail than previously, and use multiple medications,
      making them vulnerable to drug-related problems (DRPs). Practical nurses (PN)
      visit home-dwelling aged clients frequently and, thus, are ideally situated to
      identify potential DRPs and, if needed, to communicate them to physicians for
      resolution. This study developed and validated the content of a tool to be used
      by PNs for assessing DRP risks for their home-dwelling clients aged >=65 years.
      METHODS: The first draft of the tool was based on two systematic literature
      reviews and clinical experience of our research group. Content validity of the
      tool was determined by a three-round Delphi survey with a panel of 18 experts in
      geriatric care and pharmacotherapy. An agreement by >=80% of the panel on an item
      was required. RESULTS: The final tool consists of 18 items that assess risks for
      DRPs in home-dwelling aged clients. It is divided into four sections: (1) Basic
      Client Data, (2) Potential Risks for DRPs in Medication Use, (3) Characteristics
      of the Client's Care and Adherence, and (4) Recommendations for Actions to
      Resolve DRPs. CONCLUSIONS: The Delphi process resulted in a structured DRP Risk
      Assessment Tool that is focused on the highest priority DRPs that should be
      identified and resolved. The tool also assists the PNs to identify solutions to
      these problems, which is a unique feature compared to similarly purposed prior
      tools.

PMID- 24879606
TI  - A novel chemosensor with visible light excitability for sensing Zn2+ in
      physiological medium and in HeLa cells.
AB  - In the present study a novel imine-hydrazone based fluorescent chemosensor () for
      efficient and selective sensing of Zn(2+) over other biologically important metal
      ions under physiological conditions is reported. An enhancement in fluorescence
      emission intensity of the developed probe with a red shift of ~25 nm was observed
      for Zn(2+), whereas other metal ions failed to reveal any significant change in
      the emission spectra. Interestingly, the receptor functioned under completely
      physiological conditions (99.7% HEPES buffer) and has visible light excitability.
      Sensing of Zn(2+) was investigated in detail by absorption spectroscopy, emission
      spectroscopy, DFT calculation, (1)H-NMR titration experiment and ESI-MS
      experiment. The association constant between and Zn(2+) was found to be 5.58 *
      10(5) M(-1). The receptor could detect as low as 69 ppb Zn(2+). Sensing of Zn(2+)
      is proposed through switch-on of intramolecular charge transfer (ICT) and
      chelation enhanced fluorescence (CHEF) processes after the introduction of Zn(2+)
      into the free ligand. The developed receptor was non-toxic and rendered
      intracellular sensing of Zn(2+) in HeLa cells through fluorescence imaging
      studies. 

PMID- 24879608
TI  - The effect of Medicaid premiums on enrollment: a regression discontinuity
      approach.
AB  - This paper estimates the effect that premiums in Medicaid have on the length of
      enrollment of program beneficiaries. Whether and how low income-families will
      participate in the exchanges and in states' Medicaid programs depends crucially
      on the structure and amounts of the premiums they will face. I take advantage of
      discontinuities in the structure of Wisconsin's Medicaid program to identify the
      effects of premiums on enrollment for low-income families. I use a 3-year
      administrative panel of enrollment data to estimate these effects. I find an
      increase in the premium from 0 to 10 dollars per month results in 1.4 fewer
      months enrolled and reduces the probability of remaining enrolled for a full year
      by 12 percentage points, but other discrete changes in premium amounts do not
      affect enrollment or have a much smaller effect. I find no evidence of program
      enrollees intentionally decreasing labor supply in order to avoid the premiums. 

PMID- 24879607
TI  - Fluorescence in situ hybridization and optical mapping to correct scaffold
      arrangement in the tomato genome.
AB  - The order and orientation (arrangement) of all 91 sequenced scaffolds in the 12
      pseudomolecules of the recently published tomato (Solanum lycopersicum, 2n = 2x =
      24) genome sequence were positioned based on marker order in a high-density
      linkage map. Here, we report the arrangement of these scaffolds determined by two
      independent physical methods, bacterial artificial chromosome-fluorescence in
      situ hybridization (BAC-FISH) and optical mapping. By localizing BACs at the ends
      of scaffolds to spreads of tomato synaptonemal complexes (pachytene chromosomes),
      we showed that 45 scaffolds, representing one-third of the tomato genome, were
      arranged differently than predicted by the linkage map. These scaffolds occur
      mostly in pericentric heterochromatin where 77% of the tomato genome is located
      and where linkage mapping is less accurate due to reduced crossing over. Although
      useful for only part of the genome, optical mapping results were in complete
      agreement with scaffold arrangement by FISH but often disagreed with scaffold
      arrangement based on the linkage map. The scaffold arrangement based on FISH and
      optical mapping changes the positions of hundreds of markers in the linkage map,
      especially in heterochromatin. These results suggest that similar errors exist in
      pseudomolecules from other large genomes that have been assembled using only
      linkage maps to predict scaffold arrangement, and these errors can be corrected
      using FISH and/or optical mapping. Of note, BAC-FISH also permits estimates of
      the sizes of gaps between scaffolds, and unanchored BACs are often visualized by
      FISH in gaps between scaffolds and thus represent starting points for filling
      these gaps. 

PMID- 24879609
TI  - Effect of photosynthetic bacteria on water quality and microbiota in grass carp
      culture.
AB  - To investigate the effects of photosynthetic bacteria as additives on water
      quality, microbial community structure and diversity, a photosynthetic purple non
      sulfur bacteria, Rhodopseudamonas palustris, was isolated and used to remove
      nitrogen in the aquaculture water. The results of water quality showed that the
      levels of ammonia nitrogen, nitrite nitrogen, total inorganic nitrogen and total
      nitrogen in the treatment group were significantly lower (p < 0.05) than the
      nitrogen levels of the controls in an extended range. A 454-pyrosequencing
      analysis revealed that at the level of phylum, Proteobacteria and Firmicutes were
      dominant in the control group respectively, compared to the dominance of the
      phyla Proteobacteria, Bacteroidetes and Actinobacteria in the treatment group.
      The relative abundance of phyla Bacteroidetes and Actinobacteria in treatment
      witnessed an increase than that in the control. The results also indicated that
      the treatment group enjoyed a higher microbial diversity than that of the control
      group. Based on the oxygen requirement and metabolism, the authors observed that
      the water supplementation with photosynthetic bacteria could significantly
      decrease (p < 0.05) the number of nitrite reducer and anaerobic bacteria.
      Therefore, the results suggested that adding photosynthetic bacteria to water
      improves the water quality as it changes the microbial community structure.

PMID- 24879610
TI  - Smoking cessation and bone healing: optimal cessation timing.
AB  - Smoking is a worldwide epidemic. Complications related to smoking behavior
      generate an economic loss around $193 billion annually. In addition to impacting
      chronic health conditions, smoking is linked to increased perioperative
      complications in those with current or previous smoking history. Numerous studies
      have demonstrated more frequent surgical complications including higher rates of
      infection, poor wound healing, heightened pain complaints, and increased
      pulmonary morbidities in patients with a smoking history. Longer preoperative
      cessation periods also seem to correlate with reduced rates. At roughly 4 weeks
      of cessation prior to surgery, complication rates more closely reflect
      individuals without a smoking history in comparison with those that smoke within
      4 weeks of surgery. In the musculoskeletal system, a similar trend has been
      observed in smokers with higher rates of fractures, nonunions, malunions,
      infections, osteomyelitis, and lower functional scores compared to non-smoking
      patients. Unfortunately, the present literature lacks robust data suggesting a
      temporal relationship between smoking cessation and bone healing. In our review,
      we analyze pseudoarthrosis rates following spinal fusion to suggest that bone
      healing in the context of smoking behavior follows a similar time sequence as
      observed in wound healing. We also discuss the implications for further clarity
      on bone healing and smoking cessation within orthopedics including improved risk
      stratification and better identification of circumstances where adjunct therapy
      is appropriate.

PMID- 24879612
TI  - Experimental and theoretical perspectives of the Noyori-Ikariya asymmetric
      transfer hydrogenation of imines.
AB  - The asymmetric transfer hydrogenation (ATH) of imines catalyzed by the Noyori
      Ikariya [RuCl(eta6-arene)(N-arylsulfonyl-DPEN)] (DPEN=1,2-diphenylethylene-1,2
      diamine) half-sandwich complexes is a research topic that is still being
      intensively developed. This article focuses on selected aspects of this catalytic
      system. First, a great deal of attention is devoted to the N-arylsulfonyl moiety
      of the catalysts in terms of its interaction with protonated imines (substrates)
      and amines (components of the hydrogen-donor mixture). The second part is
      oriented toward the role of the eta6-coordinated arene. The final part concerns
      the imine substrate structural modifications and their importance in connection
      with ATH. Throughout the text, the summary of known findings is complemented with
      newly-presented ones, which have been approached both experimentally and
      computationally.

PMID- 24879611
TI  - A multicenter prospective study of infections related morbidity and mortality in
      cirrhosis of liver.
AB  - BACKGROUND AND AIMS: Infections are a common and serious complication among
      patients with cirrhosis. We assessed the epidemiology, risk factors, and clinical
      consequences of bacterial infections in cirrhotic patients. METHODS: In this
      multicenter prospective study, all patients with cirrhosis of liver with
      different infections were analyzed. Infections were classified as community
      acquired (CA), healthcare-associated (HCA), or hospital-acquired (HA). Site of
      infection and characteristics of bacteria were recorded; effect on liver function
      and 30-day survival were evaluated. RESULTS: One hundred and six out of 420 (25
      %) patients with cirrhosis of liver had infection. Infection rate among indoor
      patients was 37.5 % (92/245) and among outdoor patients was 8 % (14/175). Out of
      106 patients, CA, HCA, and HA were seen in 19.8 %, 50 %, and 30.2 %,
      respectively. Spontaneous bacterial peritonitis (31.1 %), urinary tract
      infections (22.6 %), and pneumonia and cellulitis (11.3 % each) were common
      infections. Gram-negative bacteria (54 %) were more common than Gram-positive
      cocci (46 %). Multidrug resistant (MDR) organisms were seen in 41.7 % of
      patients. Most of the MDR organisms were seen in HCA and HA patients. The degree
      of liver impairment was significantly more severe in patients with infection.
      Independent predictor of infection was high Child-Turcott-Pugh (CTP) class (p =
      0.006, Child B vs. A (odds ratio (OR) 3.04 95 % CI = 1.63 to 5.68) and Child C
      vs. A (OR 4.17 95 % CI = 2.12 to 8.19). Overall in-hospital mortality was 7.6 %.
      Patients with infection had increased mortality at 30-day follow up compared to
      those without infection (23.5 % vs. 2.2 %; p<0.001). CONCLUSIONS: Infections are
      one of the important causes of morbidity and mortality in patients with cirrhosis
      of liver. The most frequent infections are HCA and HA. Infection predisposes to
      deterioration of liver function and increases mortality. Cirrhotic patients
      should be monitored closely for infections especially those with Child class B
      and C.

PMID- 24879613
TI  - Combination of 2D/3D ligand-based similarity search in rapid virtual screening
      from multimillion compound repositories. Selection and biological evaluation of
      potential PDE4 and PDE5 inhibitors.
AB  - Rapid in silico selection of target focused libraries from commercial
      repositories is an attractive and cost effective approach. If structures of
      active compounds are available rapid 2D similarity search can be performed on
      multimillion compound databases but the generated library requires further
      focusing by various 2D/3D chemoinformatics tools. We report here a combination of
      the 2D approach with a ligand-based 3D method (Screen3D) which applies flexible
      matching to align reference and target compounds in a dynamic manner and thus to
      assess their structural and conformational similarity. In the first case study we
      compared the 2D and 3D similarity scores on an existing dataset derived from the
      biological evaluation of a PDE5 focused library. Based on the obtained similarity
      metrices a fusion score was proposed. The fusion score was applied to refine the
      2D similarity search in a second case study where we aimed at selecting and
      evaluating a PDE4B focused library. The application of this fused 2D/3D
      similarity measure led to an increase of the hit rate from 8.5% (1st round, 47%
      inhibition at 10 uM) to 28.5% (2nd round at 50% inhibition at 10 uM) and the best
      two hits had 53 nM inhibitory activities. 

PMID- 24879614
TI  - Point-of-care microdevices for blood plasma analysis in viral infectious
      diseases.
AB  - Each year, outbreaks of viral infections cause illness, disability, death, and
      economic loss. As learned from past incidents, the detrimental impact grows
      exponentially without effective quarantine. Therefore, rapid on-site detection
      and analysis are highly desired. In addition, for high-risk areas of viral
      contamination, close monitoring should be provided during the potential disease
      incubation period. As the epidemic progresses, a response protocol needs tobe
      rapidly implemented and the virus evolution fully tracked. For these scenarios,
      point-of-care microdevices can provide sensitive, accurate, rapid and low-cost
      analysis for a large population, especially in handling complex patient samples,
      such as blood, urine and saliva. Blood plasma can be considered as a mine of
      information containing sources and clues of biomarkers, including nucleic acids,
      immunoglobulin and other proteins, as well as pathogens for clinical diagnosis.
      However, blood plasma is also the most complicated body fluid. For targeted
      plasma biomarker detection or untargeted plasma biomarker discovery, the
      challenges can be as difficult as identifying a needle in a haystack. A useful
      platform must not only pursue single performance characteristics, but also excel
      at multiple performance parameters, such as speed, accuracy, sensitivity,
      selectivity, cost, portability, reliability, and user friendliness. Throughout
      the decades, tremendous progress has been made in point-of-care microdevices for
      viral infectious diseases. In this paper, we review fully integrated lab-on-chip
      systems for blood analysis of viral infectious disease. 

PMID- 24879615
TI  - Drug-Related Harms in Hospitalized Medicare Beneficiaries: Results From the
      Healthcare Cost and Utilization Project, 2000-2008.
AB  - OBJECTIVES: We examined drug harms in Medicare beneficiaries using the 2000-2008
      data from the Nationwide Inpatient Sample Healthcare Cost and Utilization
      Project. RESEARCH DESIGN: This is a cross-sectional study to examine the national
      estimates of potentially preventable drug-related hospitalizations and in
      hospital adverse drug events identified with the International Classification of
      Diseases codes excluding intentional harms. RESULTS: Hospitalizations related to
      drug poisoning constituted 0.8% of all Medicare hospitalizations. Annual hospital
      charges increased from $1.6 billion in 2000 to $4 billion in 2008. In-hospital
      adverse drug events were noted in 5.3% of all Medicare hospitalizations and
      increased by 90% from 2000 to 2008. Patients with extreme versus minor loss of
      function (odds ratio [OR], 2.96; 95% confidence interval [CI], 2.93-2.99) and
      with extreme versus minor likelihood of dying (OR, 2.30; 95% CI, 2.29-2.33) had
      increased odds of in-hospital adverse drug events after adjustment for age, sex,
      and race. The Medicare beneficiaries with more than 5 versus fewer than 5 listed
      diagnoses had greater odds of in-hospital adverse drug events (OR, 3.79; 95% CI,
      3.76-3.82). Each additional diagnosis at discharge was associated with a 13%
      increase in odds of in-hospital death in the Medicare beneficiaries hospitalized
      with drug-related diagnoses and with 12% increase in odds of in-hospital death in
      the Medicare beneficiaries with in-hospital adverse events. CONCLUSIONS:
      Potentially preventable drug harms are a growing clinical and financial burden.
      Comparative outpatient drug safety should be analyzed using Medicare claim
      databases. In-hospital management of drug safety should target patients with
      multimorbidity and functional decline.

PMID- 24879616
TI  - Repair of ear cartilage defects with allogenic bone marrow mesenchymal stem cells
      in rabbits.
AB  - The study aims to investigate the feasibility of repairing cartilaginous defects
      with chondrocytes induced from allogenic bone marrow mesenchymal stem cells
      (BMMSC) in rabbits' ear. BMMSCs were isolated and purified from New Zealand
      rabbits, in vitro amplified, and cultured in chondrocyte induction medium in
      order to acquire chondrocytes. After 3 weeks of induction, their phenotypes were
      confirmed as chondrocytes, then they were implanted onto novel polymeric
      scaffolds made from Poly (dl-lactide-co-glycolide) (PLGA) embedded with chitosan
      nonwoven cloth. The experimental group was transplanted with tissue engineering
      cartilaginous grafts composed of chondrogenetic BMMSC/scaffolds; the scaffold
      group was treated with scaffolds without cells, while in the control group,
      nothing was implanted. Specimens were taken at 6, 12, and 18 weeks after
      implantation, and the healing condition was observed by hematoxylin-eosin
      staining and toluidine blue staining. The right and left ears with cartilage
      defects of eighteen rabbits were randomly divided into three groups. In the
      experimental group, after 18 weeks of transplantation, the gross observation
      indicated that the cartilaginous defects were completely repaired by chondrocytes
      with smooth surface and similar color with the surrounding tissue. Hematoxylin
      eosin staining and toluidine blue staining suggested that the defective area was
      filled with mature cartilage cells with obvious lacunae but without obvious
      boundaries with the normal cartilage tissue, and that the new cartilage cells
      were evenly distributed with homogeneously dyed cytoplasm and smaller in size.
      The chondrocyte induced from allogenic BMMSC can be used to repair cartilage
      defects in rabbit's ear.

PMID- 24879617
TI  - The levels of Ki-67 positive are positively associated with lymph node metastasis
      in invasive ductal breast cancer.
AB  - Breast cancer is the most common cancer in women worldwide. In this study, we
      evaluate the potential risk factors for lymph node metastasis in invasive breast
      cancer patients with axillary dissection. 147 patients were included into this
      prospective study. The prognostic biomarkers including Ki-67, human epidermal
      growth factor receptor 2 (HER-2), hormone receptor status, p53, and lymph node
      involvement were determined by immunohistochemistry. The association between
      lymph node metastasis and these biomarkers was analyzed. Lymph node metastasis
      was found in 62 patients out of 147 patients. The high levels of Ki-67 positive
      (greater than 20 %) were positively correlated with a higher incidence of lymph
      node metastasis, including the numbers of lymph nodes that contain tumor cells
      and the lymph node metastatic rate. The high rate of positive lymphovascular
      invasion (LVI) is associated with lymph node metastasis. However, the levels of
      Ki-67 positive were not correlated with the positive rate of LVI. There was also
      no association between lymph node metastasis and other prognostic biomarkers,
      such as HER-2, estrogen receptor, progesterone receptor, and p53. In addition,
      apart from p53, the levels of Ki-67 positive were correlated with other
      prognostic biomarkers. Our data suggest that Ki-67 positivity has value as a
      prognostic and predictive biomarker in breast cancer and may be a valuable
      proliferation marker in routine diagnosis of breast cancer.

PMID- 24879618
TI  - Association study between macrophage migration inhibitory factor-173 polymorphism
      and acute myeloid leukemia in Taiwan.
AB  - Acute myeloid leukemia (AML) is the most common acute leukemia diagnosed in
      adults. Macrophage migration inhibitory factor (MIF) is a pro-inflammatory
      cytokine that plays a significant role in pathogenesis and autoimmune diseases.
      The major function of MIF is to promote the cell proliferation, migration, and
      invasion. The aim of the present study is to identify the association between MIF
      173 (rs755662) single nucleotide polymorphism (SNP) and AML in Taiwanese
      population. DNA samples extracted from 256 AML patients and 256 healthy controls
      were investigated using polymerase chain reaction followed by restriction
      fragment length polymorphism analysis. The association between MIF-173 SNP
      genotype and AML patients were assessed with SPSS software. The results show that
      the GC genotype of MIF-173 SNP is significantly higher in AML patients than in
      the healthy controls (OR 1.58, 95 % CI 1.06, P = 0.034). Carrier genotypes GC and
      CC may be a causative factor for AML cancer (OR 1.39, 95 % CI 0.95, P = 0.085).
      White blood cell count (10(3)/ul) were significantly associated with AML MIF-173
      polymorphism patients (P = 0.002). Our results in this study provide the first
      evidence that the MIF-173 polymorphism is associated with AML. MIF is a potential
      biomarker for development of AML cancer in male adult in Taiwanese population.
      Further validations in other populations are warranted.

PMID- 24879619
TI  - Holistic nurses' stories of healing of another.
AB  - The purpose of this study was to uncover the essence and meaning of healing
      through narrative accounts of holistic nurses, using a qualitative, descriptive
      design integrating narrative and story inquiry. Twenty-five stories were
      collected. Seven stories revealed personal healing and have been published in a
      prior article. Eighteen stories, the focus of this analysis, revealed healing of
      another. A hybrid method blending narrative and story guided the overall process
      for the study. Nine themes emerged describing healing of another within three
      story segments: The Call to Healing, The Experience of Healing, and Insights. The
      theme within The Call to the Healing Encounter was Drawn by Compassion to the
      Vulnerability and/or Suffering of Another. Five themes describe the Experience of
      Healing: Connection: Cocreating Relationships; Taking Risks and Dealing With
      Skeptical Colleagues; Use of Modalities and Actions as Tools in Developing Self
      as an Instrument of Healing; Profound, Ineffable Events; and Using Metaphor and
      Rituals to Describe Healing. Three themes describe Insights: Mutual
      Transformation, Change, and Reciprocity; Gratitude for the Healing Encounter; and
      Leaving a Legacy. The metastory, a reconstructed story created by the
      researchers, was the final phase of research synthesizing and demonstrating
      themes of healing of another. Results were compared to existing healing
      literature. 

PMID- 24879620
TI  - Tumour and surgery effects on cognitive functioning in high-grade glioma
      patients.
AB  - BACKGROUND: Many high-grade glioma (HGG) patients have cognitive impairments,
      which impact daily functioning. Cognitive impairments can be caused by tumour-,
      treatment-, and patient-related factors. The effect of the tumour and of surgical
      resection on cognition is, however, not well known. We investigated tumour and
      surgical effects on cognitive functioning in patients with HGG. METHODS: At
      baseline, preceding surgery, 62 patients with HGG underwent neuropsychological
      testing concerning seven cognitive domains: verbal and working memory, attention,
      executive functioning, psychomotor function, information processing speed, and
      visuoconstructive abilities. Thirty-nine patients were included in follow-up
      testing after surgery, but before subsequent treatment. Tumour size and site, use
      of anti-epileptic drugs and corticosteroids, and extent of resection were
      recorded. RESULTS: Compared to healthy controls, cognitive functioning of
      patients was significantly impaired in all domains. Prior to surgery 79 % (49 of
      62) of patients had cognitive impairment in at least one domain. At median follow
      up of 5 weeks after surgery, 59 % (23 of 39) of patients were cognitively
      impaired in at least one domain. At follow-up, 49 % showed improvement, while 23
      % declined. Left hemisphere tumour localization was associated with worse verbal
      memory (P=0.004), and larger tumours in this hemisphere with poorer executive
      functioning (P < 0.001). Changes in cognitive performance at follow-up relative
      to baseline were not related to tumour characteristics or extent of resection.
      CONCLUSIONS: Tumour-related cognitive deficits are present in a majority of HGG
      patients preceding surgery. Surgery does not result in cognitive deterioration in
      the short term in most patients.

PMID- 24879621
TI  - Melatonin improves functional outcome via inhibition of matrix metalloproteinases
      9 after photothrombotic spinal cord injury in rats.
AB  - BACKGROUND: Matrix metalloproteinases (MMPs), especially MMP-2 and MMP-9 play an
      important role in secondary inflammatory reaction and blood-central nervous
      system (CNS) barrier disruption after spinal cord injury (SCI). Theoretically, it
      is expected that early blockade of activation of MMPs can provide neuro
      protective effects from secondary tissue damage and improve functional
      neurological outcomes. The aim of this study was to investigate the expression
      and the activity of MMP-2 and MMP-9, and to determine the regulatory effect of
      melatonin on MMP expression and activity after photochemically induced SCI in
      rats. METHODS: Female Sprague-Dawley rats weighing between 250 and 300 g (age 8
      weeks) received focal ischemia by photothrombosis using Rose Bengal (RB). The
      injured animals were divided into two groups; one group received 50 mg/kg of
      melatonin intraperitoneally, starting 1 h after injury and at 12 h intervals for
      7 days, while animals in the control group received weight-adjusted doses of a
      saline vehicle. In each group, the expressions and activities of MMP-2 and MMP-9
      were assessed by Western blot and gelatin zymography at various times from 6 h to
      3 days. The locomotor function was assessed using the Basso-Beattie-Bresnahan
      (BBB) scale at 3 days after SCI and then once per week for 4 weeks. The animals
      were killed at 28 days after the injury, and the histopathology of the lesions
      was assessed. FINDINGS: The expressions and activities of MMP-9 were increased at
      6, 24, 48, and 72 h after SCI in the control group. In the melatonin-treated
      group, the expression of MMP-9 was significantly decreased at 24, 48, and 72 h
      after SCI compared with the control group, and the activity of MMP-9 was
      significantly reduced at 72 h after SCI. In contrast, there were no significant
      changes in the MMP-2 level in both groups during the experimental period.
      Melatonin treatment following photochemically induced SCI in rats significantly
      ameliorated the functional deficits. On histopathologic examination, the lesion
      size in the spinal cord after photothrombotic insult was significantly reduced by
      melatonin administration. CONCLUSIONS: This study showed that the up-regulation
      of MMP-9 correlated with the secondary damage after SCI in rats. The results of
      this study suggest that the ability of melatonin to reduce secondary tissue
      damage is intimately related to the reduction of MMP-9 expression, resulting in
      functional improvement.

PMID- 24879622
TI  - Association of caspase9 promoter polymorphisms with the susceptibility of AML in
      south Indian subjects.
AB  - Abnormal apoptosis is one of the hallmarks of cancers including acute myeloid
      leukemia (AML), as it plays a pivotal role in precisely maintaining self-renewal,
      proliferation, and differentiation properties of hematopoietic stem cells (HSCs).
      Caspase9 (CASP9), an initiator caspase activated by mitochondrial-mediated
      apoptotic pathway (intrinsic pathway), triggers cascade of effector caspases and
      executes apoptosis. Functional SNPs in CASP9 might influence the gene expression
      leading to altered apoptosis which confer the risk to AML. To test this
      hypothesis, we have analyzed four CASP9 gene polymorphisms [CASP9 - 1263A > G
      (rs4645978), CASP9 - 712C > T (rs4645981), CASP9 - 293_275del CGTGAGGTC
      AGTGCGGGGA (-293del) (rs4645982), and CASP9 Ex5 + 32G > A (rs1052576)] in 180 AML
      cases and 304 age- and sex-matched healthy controls. We performed various
      statistical analyses to determine the potential interactions between these SNPs
      and AML. The study revealed that presence of G allele at CASP9 - 1263 position
      elevates the risk of AML 1.53-fold and CT/TT genotype at CASP9 - 712 position by
      2.60-fold under dominant model of inheritance. Two CASP9 haplotypes, G-del(+)-C-A
      and G-del(+)-T-A, were found to be significantly associated with increased AML
      risk by 2.19- (95 % confidence interval (CI), 1.09-4.39; p = 0.028) and 11.75
      fold (95 % CI, 1.01-136.57; p = 0.05), respectively. Further, multidimensionality
      reduction (MDR) analysis had revealed single locus CASP9 - 712C > T SNP and four
      loci CASP9 - 1263A > G, CASP9 - 293del, CASP9 - 712C > T, and CASP9 Ex5 + 32G > A
      SNPs as highest predicting models for AML development. Our results revealed a
      significant association of two SNPs in CASP9 (-1263A > G and -712C > T) and two
      haplotypes of the four SNP combinations with AML susceptibility.

PMID- 24879623
TI  - Glutathione S-transferase T1 null genotype and laryngeal cancer risk: a meta
      analysis.
AB  - Glutathione S-transferase T1 (GSTT1) polymorphic variation has been implicated as
      a risk factor for various cancers. However, previous studies investigating the
      association between GSTT1 null genotype and laryngeal cancer risk in Asians
      reported conflicting outcomes. In the present study, the possible association of
      laryngeal cancer risk with GSTT1 null genotype was explored by a meta-analysis.
      Relevant studies were identified through a systemic search of PubMed and Chinese
      National Knowledge Infrastructure databases. Six studies with a total of 1,824
      individuals were included in the meta-analysis. The pooled odds ratio (OR) with
      95 % confidence interval (CI) was used to assess the association. Meta-analysis
      of all included studies showed that there was an obvious association between
      GSTT1 null genotype and laryngeal cancer risk in Asians (OR = 2.41, 95 % CI 1.27
      4.57, P = 0.007, I (2) = 86 %). After adjusting for heterogeneity, there was
      still an obvious association between GSTT1 null genotype and laryngeal cancer
      risk in Asians (OR = 1.75, 95 % CI 1.36-2.24, P < 0.001, I (2) = 0 %). The
      findings from the meta-analysis suggest that GSTT1 null genotype is associated
      with laryngeal cancer risk in Asians.

PMID- 24879624
TI  - Serum and bronchial aspiration fluid HE-4 levels in lung cancer.
AB  - Human epididymis 4 (HE-4) protein has been proposed as a tumor marker for lung
      and ovarian cancer. This study was designed to measure HE-4 levels in bronchial
      aspiration fluid (BAF) of patients with lung cancer and to describe the
      relationship of BAF HE-4 with known systemic increase in serum HE-4 levels. Sixty
      four patients with lung cancer, 38 with benign lung disease and 19 healthy
      subjects, were enrolled in our study. The BAF was obtained during routine
      bronchoscopic procedure in patient groups. HE-4 levels in serum and BAF were
      measured with the commercially available kit by an enzyme-linked immunosorbent
      assay. Serum HE-4 levels were significantly higher in patients with lung cancer
      group (204.2 +/- 22.9 pmol/L) than in benign lung disease group (135 +/- 26.9
      pmol/L, p = 0.001) and healthy subjects (14.8 +/- 7.0 pmol/L, p < 0.0001). No
      significant difference was observed in terms of BAF HE-4 values in two patient
      groups. BAF HE-4 levels were significantly higher than those of serum levels in
      both patient groups (p < 0.0001). Serum HE-4 level was correlated with tumor
      stage (p = 0.001) and age (p < 0.0001) in the lung cancer group. The areas under
      the receiver operating characteristic (ROC) curve of serum HE-4 was 0.784 (95 %
      confidence interval (CI), 0.701-0.867) and that of BAF HE-4 was 0.496 (95 % CI,
      0.382-0.610). This study shows that a systemic increase in serum of HE-4 is more
      prominent than a local increase of HE-4 (BAF), so this may suggest the
      feasibility of using serum instead of BAF samples for HE-4 measurements in lung
      cancer cases.

PMID- 24879625
TI  - Pituitary tumor-transforming gene 1 (PTTG1) is overexpressed in oral squamous
      cell carcinoma (OSCC) and promotes migration, invasion and epithelial-mesenchymal
      transition (EMT) in SCC15 cells.
AB  - Pituitary tumor-transforming gene 1 (PTTG1) is an important oncogenic
      transcription factor implicated in various malignancies, including oral squamous
      cell carcinoma (OSCC), a common malignancy of head and neck. Although PTTG1 is
      reportedly overexpressed in OSCC tissues, its role in human OSCC remains elusive.
      Thus, this study was conducted to explore the correlation between PTTG1
      expression and tumorigenesis of OSCC. We first examined PTTG1 mRNA and protein
      expression in 28 pairs of OSCC tissues and adjacent non-tumor tissues. PTTG1
      protein levels in 98 OSCC specimens were also evaluated by using
      immunohistochemistry. Our data showed that both mRNA and protein expression
      levels of PTTG1 in OSCC tissue specimens were markedly higher than that in the
      corresponding non-tumor tissue samples. A high level of PTTG1 protein expression
      was found in 74 out of 98 cases (75.51 %) and it was correlated with lymph node
      metastasis (P = 0.002) and tumor-node-metastasis (TNM) stage (P = 0.007) of
      patients with OSCC. Moreover, forced overexpression of PTTG1 enhanced SCC15 cell
      migration and invasion, whereas knockdown of PTTG1 resulted in reverse phenomena.
      In addition, elevated PTTG1 also increased the activities and expressions of
      matrix metalloproteinase (MMP)-2, and enhanced epithelial-mesenchymal-transition
      (EMT) process in SCC15 cells. The EMT changes were accompanied by downregulation
      of epithelial cadherin (E-cadherin) protein expression and upregulation of snail
      and vimentin. In summary, our results illustrate that PTTG1 may contribute to the
      development and progression of human OSCC.

PMID- 24879626
TI  - Clinical value of serum Epstein-Barr virus DNA assay in the diagnosis of
      nasopharyngeal carcinoma.
AB  - Serum Epstein-Barr virus DNA has been approved for diagnosing nasopharyngeal
      carcinoma (NPC). The goal of this meta-analysis was to evaluate the clinical
      value of the serum Epstein-Barr virus DNA in the diagnosis of NPC. The PubMed,
      Embase, Web of Knowledge, Chinese Wanfang Med Online, and National Knowledge
      Infrastructure (CNKI) databases were searched to identify suitable studies. The
      pooled sensitivity, specificity, positive likelihood ratio (LR+), negative
      likelihood ratio (LR-), and diagnostic odds ratio (DOR) of the serum Epstein-Barr
      virus DNA for the diagnosis of NPC were calculated. Summary receiver operating
      characteristic curves were used to summarize overall test performances. Meta-Disc
      1.4 and Stata 12.0 softwares were used to analyze the data. A total of 2,520
      patients from ten trials were subjected to meta-analysis. The summary estimates
      of the serum Epstein-Barr virus DNA for NPC diagnosis were as follows:
      sensitivity 0.69 (95 % confidence interval (CI) 0.65-0.72), specificity 0.84 (95
      % CI = 0.82-0.86), LR + 4.81 (95 % CI = 2.94-7.88), LR - 0.25 (95 % CI = 0.13
      0.48), DOR 24.65 (95 % CI = 12.64-48.07), and area under the summary receiver
      operator characteristic (SROC) curve (AUC) was 0.8979. Our study demonstrates
      that the serum Epstein-Barr virus DNA could be a useful tumor marker for NPC
      diagnosis.

PMID- 24879627
TI  - Association of Supplemental Nutrition Assistance Program (SNAP) with health
      related quality of life and disease state of HIV infected patients.
AB  - The literature on the potential clinical and non-clinical benefits of
      participation in food assistance programs for people living with HIV in developed
      countries is scarce. We conducted a cross-sectional study of 165 HIV infected
      adults to determine the impact of the Supplemental Nutrition Assistance Program
      (SNAP) on HIV disease status and health related quality of life (HQROL). There
      was no significant association between SNAP participation and disease status; CD4
      cell count (beta = 0.02, P = 0.837) and viral load (beta = 0.02, P = 0.836). The
      mean scores for all the HRQOL domains were lower compared to the US population,
      but none were associated with SNAP participation. Higher scores on the general
      health domain, were marginally associated with SNAP participation (beta = 0.16, P
      = 0.071). In this study, SNAP participation was not significantly associated with
      less disease progression, and only marginally associated with quality of life
      among this population of HIV infected individuals. 

PMID- 24879628
TI  - Correlation between use of antiretroviral adherence devices by HIV-infected youth
      and plasma HIV RNA and self-reported adherence.
AB  - Our objective was to investigate antiretroviral adherence device use by HIV
      infected youth and assess associations of device use with viral suppression and
      self-reported adherence. This cross-sectional, multisite, clinic-based study
      included data from 1,317 HIV-infected individuals 12-24 years of age that were
      prescribed antiretroviral therapy. Mean adherence in the past 7 days was 86.1 %
      and 50.5 % had an undetectable HIV RNA. Pillbox was the most commonly endorsed
      device. No specific device was independently associated with higher odds of 100 %
      adherence. Paradoxically, having an undetectable HIV RNA was inversely associated
      with use of adherence devices (OR 0.80; p = 0.04); however, among those with <100
      % adherence, higher adherence was associated with use of one or more adherence
      devices (coefficient = 7.32; p = 0.003). Our data suggest that adolescents who
      experienced virologic failure often used adherence devices which may not have
      been sufficiently effective in optimizing adherence. Therefore, other tailored
      adherence-enhancing methods need to be considered to maximize virologic
      suppression and decrease drug resistance and HIV transmission.

PMID- 24879629
TI  - A model of associative stigma on depression and anxiety among children of HIV
      infected parents in China.
AB  - Human immunodeficiency virus (HIV) carries a high level of stigma to the HIV
      infected individuals and their family members. Children of HIV-infected parents
      in China are particularly affected. The present study examined the relationship
      between associative stigma, self-esteem, optimism, anxiety and depression among
      195 children of HIV-infected parents in rural China. Findings showed that more
      than one-third (35.4 %) of the participants scored higher than cut-off for
      depression; and 23.6-67.7 % of them scored higher than cut-off for different
      types of anxiety disorders. Structural equation modelling revealed that
      associative stigma had a significant negative relationship on self-esteem and
      optimism, which were associated with higher levels of depression and anxiety. The
      indirect effects of associative stigma on depression and anxiety were
      significant. The overall model showed a satisfactory fit. Findings suggest that
      associative stigma has a significant negative impact on mental health of children
      affected by HIV. Interventions to reduce their associative stigma are warranted.

PMID- 24879631
TI  - Metabolic engineering Corynebacterium glutamicum for the L-lysine production by
      increasing the flux into L-lysine biosynthetic pathway.
AB  - The experiments presented here were based on the conclusions of our previous
      results. In order to avoid introduction of expression plasmid and to balance the
      NADH/NAD ratio, the NADH biosynthetic enzyme, i.e., NAD-dependent glyceraldehyde
      3-phosphate dehydrogenase (GADPH), was replaced by NADP-dependent GADPH, which
      was used to biosynthesize NADPH rather than NADH. The results indicated that the
      NADH/NAD ratio significantly decreased, and glucose consumption and L-lysine
      production drastically improved. Moreover, increasing the flux through L-lysine
      biosynthetic pathway and disruption of ilvN and hom, which involve in the
      branched amino acid and L-methionine biosynthesis, further improved L-lysine
      production by Corynebacterium glutamicum. Compared to the original strain C.
      glutamicum Lys5, the L-lysine production and glucose conversion efficiency
      (alpha) were enhanced to 81.0 +/- 6.59 mM and 36.45% by the resulting strain C.
      glutamicum Lys5-8 in shake flask. In addition, the by-products (i.e., L
      threonine, L-methionine and L-valine) were significantly decreased as results of
      genetic modification in homoserine dehydrogenase (HSD) and acetohydroxyacid
      synthase (AHAS). In fed-batch fermentation, C. glutamicum Lys5-8 began to produce
      L-lysine at post-exponential growth phase and continuously increased over 36 h to
      a final titer of 896 +/- 33.41 mM. The L-lysine productivity was 2.73 g l(-1) h(
      1) and the alpha was 47.06% after 48 h. However, the attenuation of MurE was not
      beneficial to increase the L-lysine production because of decreasing the cell
      growth. Based on the above-mentioned results, we get the following conclusions:
      cofactor NADPH, precursor, the flux through L-lysine biosynthetic pathway and DCW
      are beneficial to improve L-lysine production in C. glutamicum.

PMID- 24879632
TI  - Temporal integration and instrumental conditioned reinforcement.
AB  - Stimuli associated with primary reinforcement for instrumental behavior are
      widely believed to acquire the capacity to function as conditioned reinforcers
      via Pavlovian conditioning. Some Pavlovian conditioning studies suggest that
      animals learn the important temporal relations between stimuli and integrate such
      temporal information over separate experiences to form a temporal map. The
      present experiment examined whether Pavlovian conditioning can establish a
      positive instrumental conditioned reinforcer through such temporal integration.
      Two groups of rats received either delay or trace appetitive conditioning in
      which a neutral stimulus predicted response-independent food deliveries (CS1
      >US). Both groups then experienced one session of backward second-order
      conditioning of the training CS1 and a novel CS2 (CS1-CS2 pairing). Finally, the
      ability of CS2 to function as a conditioned reinforcer for a new instrumental
      response (leverpressing) was assessed. Consistent with the previous
      demonstrations of temporal integration in fear conditioning, a CS2 previously
      trained in a trace-conditioning protocol served as a better instrumental
      conditioned reinforcer after backward second-order conditioning than did a CS2
      previously trained in a delay protocol. These results suggest that an
      instrumental conditioned reinforcer can be established via temporal integration
      and raise challenges for existing quantitative accounts of instrumental
      conditioned reinforcement.

PMID- 24879633
TI  - Individual and organizational predictors of pediatric psychiatric inpatient
      admission in connecticut hospitals: a 6 month secondary analysis.
AB  - The objective of this study is to test the hypotheses that bipolar disorders or
      depressive disorders, minority status, and the presence of pediatric inpatient
      psychiatric unit will be individual predictors of pediatric psychiatric inpatient
      admission, and to provide a model that will evaluate which individual and
      organizational characteristics predict pediatric psychiatric inpatient. For this
      purpose, a secondary analysis of the medical records of 1,520 pediatric patient
      visits between January 1, 2008 and June 30, 2008, was conducted using univariate
      and multivariate logistic regression. Independent predictors of pediatric
      psychiatric inpatient admission were presence of bipolar and depressive
      disorders, greater average daily census, and increasing operating margin.
      Minority status was a significant predictor of not being admitted, as was
      presence of an anxiety disorder, greater total margin and older age. The results
      indicate that both individual and organizational factors impact disposition
      outcomes in particular subsets of pediatric patients who present to emergency
      departments for psychiatric reasons. 

PMID- 24879630
TI  - Seasonality of cardiovascular risk factors: an analysis including over 230 000
      participants in 15 countries.
AB  - OBJECTIVE: To assess the seasonality of cardiovascular risk factors (CVRF) in a
      large set of population-based studies. METHODS: Cross-sectional data from 24
      population-based studies from 15 countries, with a total sample size of 237 979
      subjects. CVRFs included Body Mass Index (BMI) and waist circumference; systolic
      (SBP) and diastolic (DBP) blood pressure; total, high (HDL) and low (LDL) density
      lipoprotein cholesterol; triglycerides and glucose levels. Within each study, all
      data were adjusted for age, gender and current smoking. For blood pressure,
      lipids and glucose levels, further adjustments on BMI and drug treatment were
      performed. RESULTS: In the Northern and Southern Hemispheres, CVRFs levels tended
      to be higher in winter and lower in summer months. These patterns were observed
      for most studies. In the Northern Hemisphere, the estimated seasonal variations
      were 0.26 kg/m(2) for BMI, 0.6 cm for waist circumference, 2.9 mm Hg for SBP, 1.4
      mm Hg for DBP, 0.02 mmol/L for triglycerides, 0.10 mmol/L for total cholesterol,
      0.01 mmol/L for HDL cholesterol, 0.11 mmol/L for LDL cholesterol, and 0.07 mmol/L
      for glycaemia. Similar results were obtained when the analysis was restricted to
      studies collecting fasting blood samples. Similar seasonal variations were found
      for most CVRFs in the Southern Hemisphere, with the exception of waist
      circumference, HDL, and LDL cholesterol. CONCLUSIONS: CVRFs show a seasonal
      pattern characterised by higher levels in winter, and lower levels in summer.
      This pattern could contribute to the seasonality of CV mortality.

PMID- 24879634
TI  - The force of impacting rain.
AB  - Drop impacts are difficult to characterize due to their transient, non-stationary
      nature. We discuss the force generated during such impacts, a key quantity for
      animals, plants, roofs or soil erosion. Although a millimetric drop has a modest
      weight, it can generate collision forces on the order of thousand times this
      weight. We measure and discuss this amplification, considering natural parameters
      such as drop radius and density, impact speed and response time of the substrate.
      We finally imagine two kinds of devices allowing us to deduce the size of the
      raindrop from impact forces. 

PMID- 24879636
TI  - Systematic validation of hypothesis-driven candidate genes for cervical cancer in
      a genome-wide association study.
AB  - A large number of genetic associations with cervical cancer have been reported in
      hypothesis-driven candidate gene studies, but most studies have not included an
      independent replication or the results have been inconsistent between studies. In
      order to independently validate these associations, we reexamined 58 candidate
      gene/regions previously reported to be associated with cervical cancer using the
      gene-based Adaptive Rank Truncated Product test in a genome-wide association
      study (GWAS) of 1034 cervical cancer patients and 3948 controls from the Swedish
      population. Of the 58 gene/regions, 8 had a nominal P value < 0.05 [tumor
      necrosis factor (TNF), P = 5.0 * 10(-4); DEAD (Asp-Glu-Ala-Asp) box helicase 1
      [DDX1], P = 2.2 * 10(-3); exonuclease 1 [EXO1], P = 4.7 * 10(-3); excision repair
      cross-complementing rodent repair deficiency, complementation group 1 [ERCC1], P
      = 0.020; transmembrane channel-like 6 and 8 genes [TMC6-TMC8], P = 0.023;
      secreted phosphoprotein 1 [SPP1], P = 0.028; v-erb-b2 avian erythroblastic
      leukemia viral oncogene homolog 2 [ERBB2], P = 0.033 and chloride channel,
      voltage-sensitive 7 [CLCN7], P = 0.047). After correction for multiple testing,
      only TNF remained statistically significant (P = 0.028). Two single-nucleotide
      polymorphisms that are in nearly perfect linkage disequilibrium (rs2857602 and
      rs2844484) contributed most to the association with TNF. However, they are not
      independent from the previously reported associations within the MHC region. The
      very low number of previously reported associations with cervical cancer that
      replicate in the Swedish population underscore the need to apply more stringent
      criteria when reporting associations, including the prerequisite of replicating
      the association as part of the original study.

PMID- 24879638
TI  - The role of verbal memory in regressions during reading is modulated by the
      target word's recency in memory.
AB  - During reading, a number of eye movements are made backward, on words that have
      already been read. Recent evidence suggests that such eye movements, called
      regressions, are guided by memory. Several studies point to the role of spatial
      memory, but evidence for the role of verbal memory is more limited. In the
      present study, we examined the factors that modulate the role of verbal memory in
      regressions. Participants were required to make regressions on target words
      located in sentences displayed on one or two lines. Verbal interference was shown
      to affect regressions, but only when participants executed a regression on a word
      located in the first part of the sentence, irrespective of the number of lines on
      which the sentence was displayed. Experiments 2 and 3 showed that the effect of
      verbal interference on words located in the first part of the sentence
      disappeared when participants initiated the regression from the middle of the
      sentence. Our results suggest that verbal memory is recruited to guide
      regressions, but only for words read a longer time ago. 

PMID- 24879635
TI  - Targeting the Warburg effect with a novel glucose transporter inhibitor to
      overcome gemcitabine resistance in pancreatic cancer cells.
AB  - Gemcitabine resistance remains a significant clinical challenge. Here, we used a
      novel glucose transporter (Glut) inhibitor, CG-5, as a proof-of-concept compound
      to investigate the therapeutic utility of targeting the Warburg effect to
      overcome gemcitabine resistance in pancreatic cancer. The effects of gemcitabine
      and/or CG-5 on viability, survival, glucose uptake and DNA damage were evaluated
      in gemcitabine-sensitive and gemcitabine-resistant pancreatic cancer cell lines.
      Mechanistic studies were conducted to determine the molecular basis of
      gemcitabine resistance and the mechanism of CG-5-induced sensitization to
      gemcitabine. The effects of CG-5 on gemcitabine sensitivity were investigated in
      a xenograft tumor model of gemcitabine-resistant pancreatic cancer. In contrast
      to gemcitabine-sensitive pancreatic cancer cells, the resistant Panc-1 and Panc
      1(GemR) cells responded to gemcitabine by increasing the expression of
      ribonucleotide reductase M2 catalytic subunit (RRM2) through E2F1-mediated
      transcriptional activation. Acting as a pan-Glut inhibitor, CG-5 abrogated this
      gemcitabine-induced upregulation of RRM2 through decreased E2F1 expression,
      thereby enhancing gemcitabine-induced DNA damage and inhibition of cell survival.
      This CG-5-induced inhibition of E2F1 expression was mediated by the induction of
      a previously unreported E2F1-targeted microRNA, miR-520f. The addition of oral CG
      5 to gemcitabine therapy caused greater suppression of Panc-1(GemR) xenograft
      tumor growth in vivo than either drug alone. Glut inhibition may be an effective
      strategy to enhance gemcitabine activity for the treatment of pancreatic cancer. 

PMID- 24879637
TI  - Flexibility within working memory and the focus of attention for sequential
      verbal information does not depend on active maintenance.
AB  - The focus of attention seems to be a static element within working memory when
      verbal information is serially presented, unless additional time is available for
      processing or active maintenance. Experiment 1 manipulated the reward associated
      with early and medial list positions in a probe recognition paradigm and found
      evidence that these nonterminal list positions could be retrieved faster and more
      accurately if participants were appropriately motivated-without additional time
      for processing or active maintenance. Experiment 2 used articulatory suppression
      and demonstrated that the underlying maintenance mechanism cannot be attributed
      to rehearsal, leaving attentional refreshing as the more likely mechanism. These
      findings suggest that the focus of attention within working memory can flexibly
      maintain nonterminal early and medial list representations at the expense of
      other list representations even when there is not additional time for processing
      or active maintenance. Maintenance seems to be accomplished through an
      attentional refreshing mechanism. 

PMID- 24879639
TI  - Genetic factors affecting gene transcription and catalytic activity of UDP
      glucuronosyltransferases in human liver.
AB  - The aim of this study was to discover cis- and trans-acting factors significantly
      affecting mRNA expression and catalytic activity of human hepatic UDP
      glucuronosyltransferases (UGTs). Transcription levels of five major hepatic UGT1A
      (UGT1A1, UGT1A3, UGT1A4, UGT1A6 and UGT1A9) and five UGT2B (UGT2B4, UGT2B7,
      UGT2B10, UGT2B15 and UGT2B17) genes were quantified in human liver tissue samples
      (n = 125) using real-time PCR. Glucuronidation activities of 14 substrates were
      measured in 47 livers. We genotyped 167 tagSNPs (single-nucleotide polymorphisms)
      in UGT1A (n = 43) and UGT2B (n = 124), as well as the known functional UGT1A1*28
      and UGT2B17 CNV (copy number variation) polymorphisms. Transcription levels of 15
      transcription factors (TFs) known to regulate these UGTs were quantified. We
      found that UGT expression and activity were highly variable among the livers
      (median and range of coefficient of variations: 135%, 74-217% and 52%, 39-105%,
      respectively). CAR, PXR and ESR1 were found to be the most important trans
      regulators of UGT transcription (median and range of correlation coefficients:
      46%, 6-58%; 47%, 9-58%; and 52%, 24-75%, respectively). Hepatic UGT activities
      were mainly determined by UGT gene transcription levels. Twenty-one polymorphisms
      were significantly (FDR-adjusted P < 0.05) associated with mRNA expression and/or
      activities of UGT1A1, UGT1A3 and UGT2B17. We found novel SNPs in the UGT2B17 CNV
      region accounting for variability in UGT2B17 gene transcription and testosterone
      glucuronidation rate, in addition to that attributable to the UGT2B17 CNV. Our
      study discovered novel pharmacogenetic markers and provided detailed insight into
      the genetic network regulating hepatic UGTs. 

PMID- 24879640
TI  - Caspase-12 ablation preserves muscle function in the mdx mouse.
AB  - Duchenne muscular dystrophy (DMD) is a devastating muscle wasting disease caused
      by mutations in dystrophin. Several downstream consequences of dystrophin
      deficiency are triggers of endoplasmic reticulum (ER) stress, including loss of
      calcium homeostasis, hypoxia and oxidative stress. During ER stress, misfolded
      proteins accumulate in the ER lumen and the unfolded protein response (UPR) is
      triggered, leading to adaptation or apoptosis. We hypothesized that ER stress is
      heightened in dystrophic muscles and contributes to the pathology of DMD. We
      observed increases in the ER stress markers BiP and cleaved caspase-4 in DMD
      patient biopsies, compared with controls, and an increase in multiple UPR
      pathways in muscles of the dystrophin-deficient mdx mouse. We then crossed mdx
      mice with mice null for caspase-12, the murine equivalent of human caspase-4,
      which are resistant to ER stress. We found that deleting caspase-12 preserved mdx
      muscle function, resulting in a 75% recovery of both specific force generation
      and resistance to eccentric contractions. The compensatory hypertrophy normally
      found in mdx muscles was normalized in the absence of caspase-12; this was found
      to be due to decreased fibre sizes, and not to a fibre type shift or a decrease
      in fibrosis. Fibre central nucleation was not significantly altered in the
      absence of caspase-12, but muscle fibre degeneration found in the mdx mouse was
      reduced almost to wild-type levels. In conclusion, we have identified heightened
      ER stress and abnormal UPR signalling as novel contributors to the dystrophic
      phenotype. Caspase-4 is therefore a potential therapeutic target for DMD. 

PMID- 24879643
TI  - In surgeons performing cardiothoracic surgery is sleep deprivation significant in
      its impact on morbidity or mortality?
AB  - A best evidence topic in cardiac surgery was written according to a structured
      protocol. The question addressed was: is there a difference in cardiothoracic
      surgery outcomes in terms of morbidity or mortality of patients operated on by a
      sleep-deprived surgeon compared with those operated by a non-sleep-deprived
      surgeon? Reported search criteria yielded 77 papers, of which 15 were deemed to
      represent the best evidence on the topic. Three studies directly related to
      cardiothoracic surgery and 12 studies related to non-cardiothoracic surgery.
      Recommendations are based on 18 121 cardiothoracic patients and 214 666 non
      cardiothoracic surgical patients. Different definitions of sleep deprivation were
      used in the studies, either reviewing surgeon's sleeping hours or out-of-hours
      operating. Surgical outcomes reviewed included: mortality rate, neurological,
      renal, pulmonary, infectious complications, length of stay, length of intensive
      care stay, cardiopulmonary bypass times and aortic-cross-clamp times. There were
      no significant differences in mortality or intraoperative complications in the
      groups of patients operated on by sleep-deprived versus non-sleep-deprived
      surgeons in cardiothoracic studies. One study showed a significant increase in
      the rate of septicaemia in patients operated on by severely sleep-deprived
      surgeons (3.6%) compared with the moderately sleep-deprived (0.9%) and non-sleep
      deprived groups (0.8%) (P = 0.03). In the non-cardiothoracic studies, 7 of the 12
      studies demonstrated statistically significant higher reoperation rate in trauma
      cases (P <0.02) and kidney transplants (night = 16.8% vs day = 6.4%, P <0.01), as
      well as higher overall mortality (P = 0.028) and morbidity (P <0.0001). There is
      little direct evidence in the literature demonstrating the effect of sleep
      deprivation in cardiothoracic surgeons on morbidity or mortality. However,
      overall the non-cardiothoracic studies have demonstrated that operative time and
      sleep deprivation can have a significant impact on overall morbidity and
      mortality. It is likely that other confounding factors concomitantly affect
      outcomes in out-of-hours surgery. 

PMID- 24879641
TI  - Inheritance of rare functional GCKR variants and their contribution to
      triglyceride levels in families.
AB  - Significant resources have been invested in sequencing studies to investigate the
      role of rare variants in complex disease etiology. However, the diagnostic
      interpretation of individual rare variants remains a major challenge, and may
      require accurate variant functional classification and the collection of large
      numbers of variant carriers. Utilizing sequence data from 458 individuals with
      hypertriglyceridemia and 333 controls with normal plasma triglyceride levels, we
      investigated these issues using GCKR, encoding glucokinase regulatory protein.
      Eighteen rare non-synonymous GCKR variants identified in these 791 individuals
      were comprehensively characterized by a range of biochemical and cell biological
      assays, including a novel high-throughput-screening-based approach capable of
      measuring all variant proteins simultaneously. Functionally deleterious variants
      were collectively associated with hypertriglyceridemia, but a range of in silico
      prediction algorithms showed little consistency between algorithms and poor
      agreement with functional data. We extended our study by obtaining sequence data
      on family members; however, functional variants did not co-segregate with
      triglyceride levels. Therefore, despite evidence for their collective functional
      and clinical relevance, our results emphasize the low predictive value of rare
      GCKR variants in individuals and the complex heritability of lipid traits. 

PMID- 24879645
TI  - Two-dimensional compressed sensing using the cross-sampling approach for low
      field MRI systems.
AB  - A compressed sensing method using a cross sampling and self-calibrated off
      resonance correction is proposed. Estimation of the magnetic field inhomogeneity
      based on image registration enables the off-resonance correction with no
      additional radio-frequency pulses or acquisitions. In addition to this advantage,
      a fast and straightforward calculation was achieved by using the first-order
      components of the magnetic field inhomogeneity. Imaging experiments using a
      phantom and a chemically fixed mouse demonstrated practical benefits in improving
      blurring and artifacts in magnetic resonance images in low field magnetic
      resonance imaging systems. 

PMID- 24879644
TI  - A system for counting fetal and maternal red blood cells.
AB  - The Kleihauer-Betke (KB) test is the standard method for quantitating fetal
      maternal hemorrhage in maternal care. In hospitals, the KB test is performed by a
      certified technologist to count a minimum of 2000 fetal and maternal red blood
      cells (RBCs) on a blood smear. Manual counting suffers from inherent
      inconsistency and unreliability. This paper describes a system for automated
      counting and distinguishing fetal and maternal RBCs on clinical KB slides. A
      custom-adapted hardware platform is used for KB slide scanning and image
      capturing. Spatial-color pixel classification with spectral clustering is
      proposed to separate overlapping cells. Optimal clustering number and total cell
      number are obtained through maximizing cluster validity index. To accurately
      identify fetal RBCs from maternal RBCs, multiple features including cell size,
      roundness, gradient, and saturation difference between cell and whole slide are
      used in supervised learning to generate feature vectors, to tackle cell color,
      shape, and contrast variations across clinical KB slides. The results show that
      the automated system is capable of completing the counting of over 60,000 cells
      (versus ~2000 by technologists) within 5 min (versus ~15 min by technologists).
      The throughput is improved by approximately 90 times compared to manual reading
      by technologists. The counting results are highly accurate and correlate strongly
      with those from benchmarking flow cytometry measurement.

PMID- 24879646
TI  - Energy preserving QMF for image processing.
AB  - Implementation of new biorthogonal filter banks (BFB) for image compression and
      denoising is performed, using test images with diversified characteristics. These
      new BFB's are linear-phase, have odd lengths, and with a critical feature,
      namely, the filters preserve signal energy very well. Experimental results show
      that the proposed filter banks demonstrate promising performance improvement over
      the filter banks of those widely used in the image processing area, such as the
      CDF 9/7.

PMID- 24879648
TI  - Continuous-time Q-learning for infinite-horizon discounted cost linear quadratic
      regulator problems.
AB  - This paper presents a method of Q-learning to solve the discounted linear
      quadratic regulator (LQR) problem for continuous-time (CT) continuous-state
      systems. Most available methods in the existing literature for CT systems to
      solve the LQR problem generally need partial or complete knowledge of the system
      dynamics. Q-learning is effective for unknown dynamical systems, but has
      generally been well understood only for discrete-time systems. The contribution
      of this paper is to present a Q-learning methodology for CT systems which solves
      the LQR problem without having any knowledge of the system dynamics. A natural
      and rigorous justified parameterization of the Q-function is given in terms of
      the state, the control input, and its derivatives. This parameterization allows
      the implementation of an online Q-learning algorithm for CT systems. The
      simulation results supporting the theoretical development are also presented. 

PMID- 24879647
TI  - Compressed sensing for bioelectric signals: a review.
AB  - This paper provides a comprehensive review of compressed sensing or compressive
      sampling (CS) in bioelectric signal compression applications. The aim is to
      provide a detailed analysis of the current trends in CS, focusing on the
      advantages and disadvantages in compressing different biosignals and its
      suitability for deployment in embedded hardware. Performance metrics such as
      percent root-mean-squared difference (PRD), signal-to-noise ratio (SNR), and
      power consumption are used to objectively quantify the capabilities of CS.
      Furthermore, CS is compared to state-of-the-art compression algorithms in
      compressing electrocardiogram (ECG) and electroencephalography (EEG) as examples
      of typical biosignals. The main technical challenges associated with CS are
      discussed along with the predicted future trends. 

PMID- 24879649
TI  - Hagleromyces gen. nov., a yeast genus in the Saccharomycetaceae, and description
      of Hagleromyces aurorensis sp. nov., isolated from water tanks of bromeliads.
AB  - Three strains of a novel yeast species were isolated from water tanks
      (phytotelmata) of a bromeliad species collected in the state of Tocantins,
      Brazil. Analysis of sequences for the region spanning the SSU rRNA gene, the
      internal transcribed spacer, the 5.8S rRNA gene and the D1/D2 domains of the LSU
      rRNA gene and RNA polymerase II gene showed that these novel yeasts belong to a
      species that is distinct from all recognized ascomycetous yeast species. Based on
      the results of gene sequence analyses, a novel species representing a new genus
      in the Saccharomycetaceae is proposed. The novel species is assigned to the genus
      Hagleromyces gen. nov. The three isolates of the novel yeast species failed to
      form sexual spores alone or in mixtures. The name Hagleromyces aurorensis sp.
      nov. is proposed to accommodate these isolates. The type strain of H. aurorensis
      sp. nov. is UFMG-CM-Y311(T) ( = CBS 13264(T)). 

PMID- 24879650
TI  - Spatiotemporal modeling of ozone levels in Quebec (Canada): a comparison of
      kriging, land-use regression (LUR), and combined Bayesian maximum entropy-LUR
      approaches.
AB  - BACKGROUND: Ambient air ozone (O3) is a pulmonary irritant that has been
      associated with respiratory health effects including increased lung inflammation
      and permeability, airway hyperreactivity, respiratory symptoms, and decreased
      lung function. Estimation of O3 exposure is a complex task because the pollutant
      exhibits complex spatiotemporal patterns. To refine the quality of exposure
      estimation, various spatiotemporal methods have been developed worldwide.
      OBJECTIVES: We sought to compare the accuracy of three spatiotemporal models to
      predict summer ground-level O3 in Quebec, Canada. METHODS: We developed a land
      use mixed-effects regression (LUR) model based on readily available data (air
      quality and meteorological monitoring data, road networks information, latitude),
      a Bayesian maximum entropy (BME) model incorporating both O3 monitoring station
      data and the land-use mixed model outputs (BME-LUR), and a kriging method model
      based only on available O3 monitoring station data (BME kriging). We performed
      leave-one-station-out cross-validation and visually assessed the predictive
      capability of each model by examining the mean temporal and spatial distributions
      of the average estimated errors. RESULTS: The BME-LUR was the best predictive
      model (R2 = 0.653) with the lowest root mean-square error (RMSE ;7.06 ppb),
      followed by the LUR model (R2 = 0.466, RMSE = 8.747) and the BME kriging model
      (R2 = 0.414, RMSE = 9.164). CONCLUSIONS: Our findings suggest that errors of
      estimation in the interpolation of O3 concentrations with BME can be greatly
      reduced by incorporating outputs from a LUR model developed with readily
      available data.

PMID- 24879651
TI  - The prevalence and psychological costs of household violence by family members
      against women with disabilities in Cambodia.
AB  - Women with disabilities (WWDs) are at triple jeopardy due to the combined risks
      associated with gender, disability, and violence. Not only are WWDs marginalized
      socially but the violence against them in their own homes is largely neglected in
      domestic violence research. Evidence from developing countries is particularly
      sparse. A cross-sectional survey conducted in Cambodia found rates of violence by
      household members besides intimate partners were significantly higher among WWDs
      than non-disabled women. This violence engendered increased levels of
      psychological distress and higher rates of physical injury but low rates of
      disclosure to health workers and other formal sources of potential support.
      Community-based strategies are recommended to radically change social and
      cultural attitudes, beliefs, and responses to WWDs who are victims of household
      violence to reduce negative social reactions toward them and to make it safer for
      them to disclose and receive psychosocial, legal, and other necessary support for
      this underreported type of violence. 

PMID- 24879652
TI  - Jane Doe: a cautionary tale for case reports.
AB  - Historically, clinical case reports have played an essential role in the
      professional communication of medical and psychiatric knowledge. Case reports
      continue to play important roles in the initial identification of new syndromes
      or unusual variants of established conditions. Case reports and case series also
      serve to alert clinicians to preliminary evidence of the efficacy of novel
      treatments or adaptations to new populations. The Jane Doe Case provides a
      seminal example of the ethical/medico-legal dilemma arising from a patient's
      right to confidentiality versus the principle of independent review/replication
      as a necessary requirement for scientific credibility. As a result of being the
      subject of dueling case reports concerning the validity of her delayed recall of
      childhood sexual abuse, Jane Doe's identity was revealed. Consequently, she
      suffered significant emotional distress, bankruptcy, and the end of her career as
      a naval officer and aviator. Current medical journal guidelines call for
      protection of confidentiality of the patient's identity; yet, scientific
      credibility requires the possibility of an independent outside review if there
      are legitimate reasons to question facts or claims advanced in a case report. A
      potential solution is proposed as a starting point for resolving the dilemma
      posed for case study subjects and authors by the conflicting requirements of
      patient confidentiality and, if warranted, the possibility of an independent
      scientific review. 

PMID- 24879653
TI  - Exposure to fine particulate matter during pregnancy and risk of preterm birth
      among women in New Jersey, Ohio, and Pennsylvania, 2000-2005.
AB  - BACKGROUND: Particulate matter <= 2.5 MUm in aerodynamic diameter (PM2.5) has
      been variably associated with preterm birth (PTB). OBJECTIVE: We classified PTB
      into four categories (20-27, 28-31, 32-34, and 35-36 weeks completed gestation)
      and estimated risk differences (RDs) for each category in association with a 1
      MUg/m3 increase in PM2.5 exposure during each week of gestation. METHODS: We
      assembled a cohort of singleton pregnancies that completed >= 20 weeks of
      gestation during 2000-2005 using live birth certificate data from three states
      (Pennsylvania, Ohio, and New Jersey) (n = 1,940,213; 8% PTB). We estimated mean
      PM2.5 exposures for each week of gestation from monitor-corrected Community Multi
      Scale Air Quality modeling data. RDs were estimated using modified Poisson linear
      regression and adjusted for maternal race/ethnicity, marital status, education,
      age, and ozone. RESULTS: RD estimates varied by exposure window and outcome
      period. Average PM2.5 exposure during the fourth week of gestation was positively
      associated with all PTB outcomes, although magnitude varied by PTB category
      [e.g., for a 1-MUg/m3 increase, RD = 11.8 (95% CI: -6, 29.2); RD = 46 (95% CI:
      23.2, 68.9); RD = 61.1 (95% CI: 22.6, 99.7); and RD = 28.5 (95% CI: -39, 95.7)
      for preterm births during 20-27, 28-31, 32-34, and 35-36 weeks, respectively].
      Exposures during the week of birth and the 2 weeks before birth also were
      positively associated with all PTB categories. CONCLUSIONS: Exposures beginning
      around the time of implantation and near birth appeared to be more strongly
      associated with PTB than exposures during other time periods. Because particulate
      matter exposure is ubiquitous, evidence of effects of PM2.5 exposure on PTB, even
      if small in magnitude, is cause for concern.

PMID- 24879655
TI  - Using systems science for population health management in primary care.
AB  - OBJECTIVES: Population health management is becoming increasingly important to
      organizations managing and providing primary care services given ongoing changes
      in health care delivery and payment systems. The objective of this study is to
      show how systems science methodologies could be incorporated into population
      health management to compare different interventions and improve health outcomes.
      METHODS: The New York Academy of Medicine Cardiovascular Health Simulation model
      (an agent-based model) and data from the Behavioral Risk Factor Surveillance
      System were used to evaluate a lifestyle program that could be implemented in
      primary care practice settings. The program targeted Medicare-age adults and
      focused on improving diet and exercise and reducing weight. RESULTS: The
      simulation results suggest that there would be significant reductions projected
      in the proportion of the Medicare-age population with diabetes after the
      implementation of the proposed lifestyle program for a relatively long term (3
      and 5 years). Similar results were found for the subpopulations with high
      cholesterol, but the proposed intervention would not have a significant effect in
      the proportion of the population with hypertension over a time period of <5
      years. CONCLUSIONS: Systems science methodologies can be useful to compare the
      health outcomes of different interventions. These tools can become an important
      component of population health management because they can help managers and
      other decision makers evaluate alternative programs in primary care settings.

PMID- 24879654
TI  - A longitudinal study of urinary phthalate excretion in 58 full-term and 67
      preterm infants from birth through 14 months.
AB  - BACKGROUND: Some phthalates have shown antiandrogenic effects in rat offspring.
      Premature infants may be exposed to high amounts of specific phthalates during
      hospitalization, and thus are potentially at risk. OBJECTIVE: We evaluated
      longitudinal phthalate exposure and metabolism in full-term (FT) and preterm (PT)
      infants. METHODS: Fifty-eight FT and 67 PT (gestational age, 24.7-36.6 weeks)
      infants were recruited at birth and followed until 14 months (nine times).
      Urinary concentrations of metabolites of diethyl phthalate (DEP), dibutyl
      phthalate isomers (DiBP and DnBP), butylbenzyl phthalate (BBzP), di(2-ethylhexyl)
      phthalate (DEHP), and diisononyl phthalate (DiNP) were measured in 894 samples.
      Daily intake and a hazard index for antiandrogenic effects were estimated, and
      excretion patterns of DEHP and DiNP metabolites were analyzed. RESULTS:
      Metabolites of BBzP, DiNP, and DEHP were 5-50 times higher at day 7 (D7) and
      month 1 (M1) in PT than in FT infants. Thereafter, metabolite concentrations were
      similar between the two groups. The estimated hazard index for combined DiBP,
      DnBP, BBzP, and DEHP exposures 7 days after birth exceeded the antiandrogenic
      threshold in > 80% of PT and > 30% of FT infants, and after M2, in 30% of all
      infants. The excretion pattern of DEHP and DiNP metabolites changed with age.
      CONCLUSION: Most PT infants and approximately one-third of healthy FT newborns
      were exposed to phthalates during early life at a potentially harmful level
      according to the European Food Safety Authority's recommended limits of daily
      exposure. Changes in the relative proportions of secondary phthalate metabolites
      over time were consistent with maturation of infant metabolic pathways during the
      first year of life. Further research is needed on the health effects of phthalate
      exposures and the influence of changes in metabolic capacity in neonates and
      infants.

PMID- 24879656
TI  - Addiction to sugar and its link to health morbidity: a primer for newer primary
      care and public health initiatives in Malaysia.
AB  - OBJECTIVES: The average consumption of sugar in the Malaysian population has
      reached an alarming rate, exceeding the benchmark recommended by experts. This
      article argues the need of a paradigm shift in the management of sugar
      consumption in the country through evidence derived from addiction research.
      METHODS: "Food addiction" could lead to high levels of sugar consumption. This
      probable link could accelerate the development of diabetes and obesity in the
      community. A total of 94 reports and studies that describe the importance of
      addiction theory-based interventions were found through a search on PubMed,
      Google Scholar, and Academic Search Complete. RESULTS: Research in the field of
      addiction medicine has revealed the addictive potential of high levels of sugar
      intake. Preexisting health promotion strategies could benefit from the
      integration of the concept of sugar addiction. A targeted intervention could
      yield more positive results in health outcomes within the country. CONCLUSION:
      Current literature seems to support food environment changes, targeted health
      policies, and special consultation skills as cost-effective remedies to curb the
      rise of sugar-related health morbidities.

PMID- 24879657
TI  - The vacuum-assisted closure (V.A.C(r)) system for surgical site infection with
      involved vascular grafts.
AB  - BACKGROUND: In vascular surgery, surgical site infection is the most common
      postoperative morbidity, occurring in 5-10% of vascular patients. The optimal
      management of surgical site infection with involved lower limb vascular grafts
      remains controversial. We present our 6-year results of using the V.A.C.(r)
      system in surgical site infection with involved vascular grafts. METHODS: A
      retrospective 6-year review of patient who underwent a VAC(r) therapy for
      postoperative surgical site infection in lower limb with involved vascular grafts
      in our department between January 2006 and December 2011. V.A.C therapy was used
      in 40 patients. All patients underwent surgical wound revision with VAC(r)
      therapy and antibiotics. RESULTS: The mean time of use of the V.A.C. system was
      14.2 days. After mean of 12 days in 34 of 40 patients, in whom the use of VAC(r)
      therapy resulted in delayed primary closure or healing by secondary intention.
      The mean postoperative follow-up time was 61.67 months, during which 3 patients
      died. CONCLUSION: We showed that the V.A.C.(r) system is valuable for managing
      specifically surgical site infection with involved vascular grafts. Using the
      V.A.C.(r) system, reoperation rates are reduced; 85% of patients avoided graft
      replacement.

PMID- 24879658
TI  - Systemic lupus erythematosus impairs memory cognitive tests not affected by
      depression.
AB  - OBJECTIVE: Our aim was to assess the contribution of depression to cognitive
      impairment in patients with systemic lupus erythematosus (SLE). METHODS: Clinical
      features, education, age, and Hospital Anxiety and Depression Scale (HADS) were
      evaluated in 82 patients with SLE and 22 healthy controls, all Chilean women. The
      Cambridge Neuropsychological Test Automated Battery (CANTAB eclipseTM) assessing
      attention, spatial memory, and learning and executive function domains was
      applied. Cognitive deficit definition: a cut-off for definite impairment was
      defined as a score below -2 standard deviations in at least one outcome measure
      in two or more domains. ANCOVA with stepwise selection evaluated influences of
      health status (SLE or control), age, education, and HADS depression and anxiety
      scores on cognitive outcomes. To avoid overfitting, a shrinkage method was
      performed. Also, adjusted p-values for multiple comparisons were obtained.
      RESULTS: Cognitive deficit affected 16 (20%) patients, and no controls (p=0.039).
      Median HADS depression score in SLE patients was 6 (range 0-19) and in controls
      was 0 (0-19), p<0.001). ANCOVA and shrinkage models showed that worse cognitive
      performance in sustained attention and spatial working memory tests was explained
      by the presence of SLE but not depression, whereas depression only affected a
      measure of executive function (I/ED Stages completed). CONCLUSION: Depression has
      a limited role in cognitive impairment in SLE. Impairments in sustained attention
      and spatial working memory are distinctly influenced by yet-unknown disease
      intrinsic factors.

PMID- 24879659
TI  - Three cases of lupus nephritis patients with serum interleukin-32gamma detection.
AB  - PURPOSE: Interleukin-32 (IL-32) is an inflammatory cytokine that is associated
      with the pathogenesis of several connective tissue diseases. We measured serum IL
      32gamma concentrations of systemic lupus erythematosus (SLE) patients. METHODS:
      Serum samples were obtained from SLE patients (n = 51), and healthy controls (n =
      15). Serum IL-32 concentrations were measured using ELISA. Clinical information
      was obtained from medical records. RESULTS: Serum IL-32gamma was detectable in
      three cases of SLE patients, whereas it was not detected in any healthy controls.
      Case 1: a 44-year-old female with lupus nephritis (LN) (Class II) and
      antiphospholipid antibody syndrome. Serum IL-32gamma was 5.1 pg/ml. Case 2: a 30
      year-old female with a history of diffuse proliferative LN (Class IV G (A/C)) and
      pulmonary hemorrhage. Serum IL-32gamma was 8.9 pg/ml. Case 3: a 45-year-old
      female with chronic LN. Serum IL-32gamma was 9.1 pg/ml. All three cases of IL
      32gamma-detectable patients had histories of LN and one had an active disease. In
      the context of LN, serum IL-32gamma was detectable in 18.8% (three of 16) of SLE
      patients with histories of LN. CONCLUSION: We suppose that IL-32gamma could
      contribute to the pathogenesis of renal diseases in some LN patients.

PMID- 24879661
TI  - Histology and clinical outcome of benign and malignant vascular lesions primary
      to feline cervical lymph nodes.
AB  - A novel form of primary feline hemangiosarcoma and additional cases of plexiform
      vascularization in the cervical lymph nodes are reported. Sixteen cases of feline
      lymphadenopathy attributed to abnormal vascular proliferation were identified and
      evaluated. Most of these lesions were diagnosed histologically as
      hemangiosarcoma. However, lesions of plexiform vascularization, with and without
      areas of putative malignant transformation, were also identified. Mean age of the
      cats was 11 years (range, 3-16 years) with most being domestic shorthair and
      medium hair (13). Two domestic long hair and 1 Maine Coon were identified.
      Excisional nodal biopsy was performed in 15 cases and incisional biopsy in 1
      case. Six cats were euthanized due to their disease. Survival times ranged from
      <= 1 month to >= 30 months. We provide a new clinical differential for cervical
      lymphadenopathy in cats that is not widely recognized. Proper identification of
      primary nodal vascular lesions in cats will enable further characterization of
      clinical features and biologic behavior to determine specific therapy.

PMID- 24879660
TI  - Ultrastructural abnormalities of the trabecular meshwork extracellular matrix in
      Cyp1b1-deficient mice.
AB  - Cytochrome P450 1B1 (CYP1B1) is highly expressed in human and murine ocular
      tissues during development. Mutations in this gene are implicated in the
      development of primary congenital glaucoma (PCG) in humans. Mice deficient in
      Cyp1b1 (Cyp1b1(-/-) ) present developmental abnormalities similar to human
      primary congenital glaucoma. The present work describes the ultrastructural
      morphology of the iridocorneal angle of 21 eyes from 1-week-old to 8-month-old
      Cyp1b1(-/-) mice. Morphometric and semiquantitative analysis of the data revealed
      that 3-week-old Cyp1b1(-/-) mice present a significantly (P < .005) decreased
      amount of trabecular meshwork (TM) collagen and higher TM endothelial cell and
      collagen lesion scores (P < .005) than age-matched controls. Collagen loss and
      lesion scores were progressively increased in older animals, with 8-month-old
      animals presenting severe atrophy of the TM. Our findings advance the
      understanding of the effects of CYP1B1 mutations in TM development and primary
      congenital glaucoma, as well as suggest a link between TM morphologic alterations
      and increased intraocular pressure. 

PMID- 24879662
TI  - The impact of change in physical activity on change in arterial stiffness in
      overweight or obese sedentary young adults.
AB  - Arterial stiffness is associated with cardiovascular events and mortality.
      Lifestyle factors such as physical activity (PA) may reduce arterial stiffness.
      The purpose of this study is to determine the impact of change in PA on 1-year
      change in arterial stiffness in 274 overweight/obese sedentary young adults. The
      Slow Adverse Vascular Effects of excess weight (SAVE) trial was a study
      evaluating the relationships between weight loss, dietary sodium, and vascular
      health. PA was measured with the ActiGraph AM7164 accelerometer. Intensity of
      activity was determined using established cut-points. Arterial stiffness was
      assessed by brachial-ankle pulse wave velocity (baPWV) using an automated device.
      Analysis of covariance compared changes in total accelerometer counts,
      minutes/day in light-intensity PA (LPA), moderate-to-vigorous PA (MVPA), and
      sedentary time, by categories of change in baPWV. Models were adjusted for time
      since baseline visit, age, sex, race, homeostatis model of assessment of insulin
      resistance, mean arterial pressure, heart rate, and weight change. Total
      accelerometer counts and time spent in MVPA increased from baseline to 12 months
      while time spent in LPA significantly decreased. Mean baPWV was similar at each
      time point. Those who showed decreased baPWV also showed an increase in total
      accelerometer counts per day and time spent in MVPA in the fully adjusted models
      (p<0.001). Changes in sedentary time and time spent in LPA were not associated
      with changes in baPWV. These results indicate that even modest increases in MVPA
      can reduce arterial stiffness, a risk factor for future cardiovascular events.

PMID- 24879664
TI  - Comment on: antiretroviral treatment French guidelines 2013: economics
      influencing science.

PMID- 24879666
TI  - Favourable outcome in the treatment of carbapenem-resistant Enterobacteriaceae
      urinary tract infection with high-dose tigecycline.

PMID- 24879665
TI  - Doripenem population pharmacokinetics and dosing requirements for critically ill
      patients receiving continuous venovenous haemodiafiltration.
AB  - OBJECTIVES: Doripenem is a newer carbapenem with little data available to guide
      effective dosing during renal replacement therapy in critically ill patients. The
      objective of this study was to determine the population pharmacokinetics of
      doripenem in critically ill patients undergoing continuous venovenous
      haemodiafiltration (CVVHDF) for acute kidney injury (AKI). METHODS: This was an
      observational pharmacokinetic study in 12 infected critically ill adult patients
      with AKI undergoing CVVHDF and receiving 500 mg of doripenem intravenously every
      8 h as a 60 min infusion. Serial blood samples were taken on 2 days of treatment
      and used for population pharmacokinetic analysis with S-ADAPT. RESULTS: The
      median (IQR) age was 62 (53-71) years, the median (IQR) weight was 77 (67-96) kg
      and the median (IQR) APACHE II score was 29 (19-32). The median blood, dialysate
      and replacement fluid rates were 200, 1000 and 1000 mL/h, respectively. A two
      compartment linear model with doripenem clearance described by CVVHDF, renal or
      non-renal mechanisms was most appropriate. The mean value for total doripenem
      clearance was 4.46 L/h and volume of distribution was 38.0 L. Doripenem clearance
      by CVVHDF was significantly correlated with the replacement fluid flow rate and
      accounted for ~30%-37% of total clearance. A dose of 500 mg intravenously every 8
      h achieved favourable pharmacokinetic/pharmacodynamics for all patients up to an
      MIC of 4 mg/L. CONCLUSIONS: This is the first paper describing the
      pharmacokinetics/pharmacodynamics of doripenem in critically ill patients with
      AKI receiving CVVHDF. A dose of 500 mg intravenously every 8 h was appropriate
      for our CVVHDF settings for infections caused by susceptible bacteria.

PMID- 24879667
TI  - Extended-spectrum and AmpC beta-lactamase-producing Escherichia coli in broilers
      and people living and/or working on broiler farms: prevalence, risk factors and
      molecular characteristics.
AB  - OBJECTIVES: The objectives of this study were to: estimate the prevalence of
      extended-spectrum beta-lactamase (ESBL)- and AmpC beta-lactamase-producing
      Escherichia coli carriage among broiler farmers, their family members and
      employees; identify and quantify risk factors for carriage, with an emphasis on
      contact with live broilers; and compare isolates from humans and broilers within
      farms with respect to molecular characteristics to gain insight into transmission
      routes. METHODS: A cross-sectional prevalence study was conducted on 50 randomly
      selected Dutch broiler farms. Cloacal swabs were taken from 20 randomly chosen
      broilers. Faecal swabs were returned by 141 individuals living and/or working on
      47 farms. ESBL/AmpC-producing E. coli were isolated and, for selected isolates,
      phylogenetic groups, plasmids and sequence types were determined. Questionnaires
      were used for risk factor analysis. RESULTS: All sampled farms were positive,
      with 96.4% positive pooled broiler samples. The human prevalence was 19.1%, with
      14.3% and 27.1% among individuals having a low and a high degree of contact with
      live broilers, respectively. Five pairs of human-broiler isolates had identical
      genes, plasmid families and E. coli sequence types, showing clonal transmission.
      Furthermore, similar ESBL/AmpC genes on the same plasmid families in different E.
      coli sequence types in humans and broilers hinted at horizontal gene transfer.
      CONCLUSIONS: The prevalence among people on broiler farms was higher than in
      previous studies involving patients and the general population. Furthermore, an
      increased risk of carriage was shown among individuals having a high degree of
      contact with live broilers. The (relative) contribution of transmission routes
      that might play a role in the dissemination of ESBL/AmpC-encoding resistance
      genes to humans on broiler farms should be pursued in future studies.

PMID- 24879663
TI  - Characterization of plasmids carrying the blaOXA-24/40 carbapenemase gene and the
      genes encoding the AbkA/AbkB proteins of a toxin/antitoxin system.
AB  - BACKGROUND: Carbapenem-resistant Acinetobacter baumannii (CRAb) is a major source
      of nosocomial infections in Spain associated with the production of OXA-58-like
      or OXA-24/40-like beta-lactamase enzymes. We analysed the plasmids carrying the
      bla(OXA-24/40)-like gene in CRAb isolates obtained a decade apart. METHODS: The
      presence of beta-lactamases was screened for by PCR (metallo-beta-lactamases,
      carbapenem-hydrolysing class D beta-lactamases, GES and KPC) in 101 CRAb isolates
      obtained in two multicentre studies (GEIH/REIPI-Ab-2000 and GEIH/REIPI-Ab-2010; n
      = 493 Acinetobacter spp). We analysed the distribution and characterization of
      the plasmids carrying the bla(OXA-24/40)-like gene and sequenced two plasmids,
      AbATCC223p (2000) and AbATCC329p (2010) from A. baumannii ATCC 17978
      transformants. RESULTS: Acquisition of the bla(OXA-24/40)-like gene was the main
      mechanism underlying resistance to carbapenems (48.7% in 2000 compared with 51.6%
      in 2010). This gene was mainly isolated in ST2 A. baumannii strains in both
      studies, although some novel STs (ST79 and ST80) appeared in 2010. The gene was
      located in plasmids (8-12 kbp) associated with the repAci2 or repAci2/repGR12
      types. The sequences of AbATCC223p (8840 bp) and AbATCC329p (8842 bp) plasmids
      were similar, particularly regarding the presence of the genes encoding the
      AbkA/AbkB proteins associated with the toxin/antitoxin system. Moreover, the
      abkA/abkB gene sequences (>96% identity) were also located in plasmids harbouring
      the bla(OXA-58)-like gene. CONCLUSIONS: The action of OXA-24/40 and OXA-58 beta
      lactamase-like enzymes represents the main mechanism underlying resistance to
      carbapenems in Spain in the last decade. AbkA/AbkB proteins in the
      toxin/antitoxin system may be involved in the successful dissemination of
      plasmids carrying the bla(OXA-24/40)-like gene, and probably also the bla(OXA-58)
      like gene, thus contributing to the plasmid stability.

PMID- 24879668
TI  - Antimicrobial drug resistance among clinically relevant bacterial isolates in sub
      Saharan Africa: a systematic review.
AB  - BACKGROUND: Little is known about the prevalence of antimicrobial resistance
      (AMR) amongst bacterial pathogens in sub-Saharan Africa (sSA), despite calls for
      continent-wide surveillance to inform empirical treatment guidelines. METHODS: We
      searched PubMed and additional databases for susceptibility data of key pathogens
      for surveillance, published between 1990 and 2013. Extracted data were
      standardized to a prevalence of resistance in populations of isolates and
      reported by clinical syndrome, microorganism, relevant antimicrobial drugs and
      region. RESULTS: We identified 2005 publications, of which 190 were analysed.
      Studies predominantly originated from east sSA (61%), were hospital based (60%),
      were from an urban setting (73%) and reported on isolates from patients with a
      febrile illness (42%). Quality procedures for susceptibility testing were
      described in <50% of studies. Median prevalence (MP) of resistance to
      chloramphenicol in Enterobacteriaceae, isolated from patients with a febrile
      illness, ranged between 31.0% and 94.2%, whilst MP of resistance to third
      generation cephalosporins ranged between 0.0% and 46.5%. MP of resistance to
      nalidixic acid in Salmonella enterica Typhi ranged between 15.4% and 43.2%. The
      limited number of studies providing prevalence data on AMR in Gram-positive
      pathogens or in pathogens isolated from patients with a respiratory tract
      infection, meningitis, urinary tract infection or hospital-acquired infection
      suggested high prevalence of resistance to chloramphenicol,
      trimethoprim/sulfamethoxazole and tetracycline and low prevalence to third
      generation cephalosporins and fluoroquinolones. CONCLUSIONS: Our results indicate
      high prevalence of AMR in clinical bacterial isolates to antimicrobial drugs
      commonly used in sSA. Enhanced approaches for AMR surveillance are needed to
      support empirical therapy in sSA.

PMID- 24879669
TI  - Tigecycline in treatment of multidrug-resistant Gram-negative bacillus urinary
      tract infections: a systematic review.
AB  - OBJECTIVES: To review cases of multidrug-resistant (MDR) Gram-negative bacillus
      urinary tract infections (UTIs) treated with tigecycline and the literature
      related to this subject. METHODS: We performed a systematic review of the
      literature identifying patients with MDR Gram-negative bacillus UTIs treated with
      tigecycline. RESULTS: Fourteen cases describing treatment of UTIs caused by MDR
      Gram-negative bacilli with tigecycline are reviewed. Favourable clinical outcomes
      were noted in 11 of 14 cases. An initial favourable microbiological outcome was
      noted in 12 cases. Post-treatment cultures in two cases were positive for
      tigecycline-resistant organisms. CONCLUSIONS: The clinical efficacy of
      tigecycline for treatment of UTIs has not been extensively evaluated. Based on
      the available literature, tigecycline appears to have efficacy in some patients
      with MDR Gram-negative bacillus UTIs. Further research in this area is needed to
      fully elucidate the role of tigecycline in treating such patients.

PMID- 24879670
TI  - Battle Scars.

PMID- 24879671
TI  - The Anti-inflammatory and Matrix Restorative Mechanisms of Platelet-Rich Plasma
      in Osteoarthritis: Letter to the Editor.

PMID- 24879672
TI  - The Anti-inflammatory and Matrix Restorative Mechanisms of Platelet-Rich Plasma
      in Osteoarthritis: Response to Patel and Dhillon.

PMID- 24879673
TI  - Anti-inflammatory and Matrix Restorative Mechanisms of Platelet-Rich Plasma in
      Osteoarthritis: Letter to the Editor.

PMID- 24879674
TI  - Anti-inflammatory and Matrix Restorative Mechanisms of Platelet-Rich Plasma in
      Osteoarthritis: Response to Andia and Maffulli.

PMID- 24879675
TI  - Mesenchymal Stem Cell Injection for Osteochondral Lesions of the Talus: Letter to
      the Editor.

PMID- 24879676
TI  - Mesenchymal Stem Cell Injection for Osteochondral Lesions of the Talus: Response.

PMID- 24879677
TI  - Interval Throwing Program and Baseball Pitching: Letter to the Editor.

PMID- 24879678
TI  - Interval Throwing Program and Baseball Pitching: Response.

PMID- 24879679
TI  - Corrigendum.

PMID- 24879680
TI  - Effects of different broiler production systems on health care costs in the
      Netherlands.
AB  - This study analyzed the effects of different broiler production systems on health
      care costs in the Netherlands. In addition to the conventional production system,
      the analysis also included 5 alternative animal welfare systems representative of
      the Netherlands. The study was limited to the most prevalent and economically
      relevant endemic diseases in the broiler farms. Health care costs consisted of
      losses and expenditures. The study investigated whether higher animal welfare
      standards increased health care costs, in both absolute and relative terms, and
      also examined which cost components (losses or expenditures) were affected and,
      if so, to what extent. The results show that health care costs represent only a
      small proportion of total production costs in each production system. Losses
      account for the major part of health care costs, which makes it difficult to
      detect the actual effect of diseases on total health care costs. We conclude
      that, although differences in health care costs exist across production systems,
      health care costs only make a minor contribution to the total production costs
      relative to other costs, such as feed costs and purchase of 1-d-old chicks. 

PMID- 24879681
TI  - The effect of perch access during pullet rearing and egg laying on physiological
      measures of stress in White Leghorns at 71 weeks of age.
AB  - Egg laying strains of chickens have a strong motivation to perch. Providing caged
      chickens with perches allows them to perform their natural perching behavior and
      also improves their musculoskeletal health due to exercise. Little is known about
      the effect of perch access for hens on physiological measures of stress. Our
      hypothesis was that denying chickens access to perches would elicit a stress
      response. The objective of this study was to determine the effect of perch access
      during all or part of life cycle on physiological homeostasis in caged 71-wk-old
      White Leghorn hens. A total of 1,064 chicks were assigned randomly to cages with
      and without perches (n = 14 pullet cages/perch treatment) on day of hatch. As
      pullets aged, chicks were removed from cages to provide more space. At 17 wk of
      age, 324 chickens in total were assigned to laying cages consisting of 4
      treatments with 9 replicates per treatment. Treatment 1 chickens never had access
      to perches during their life cycle. Treatment 2 chickens had access to perches
      only from 17 to 71 wk of age (laying phase). Treatment 3 chickens had access to
      perches only from hatch to 16.9 wk of age (pullet phase). Treatment 4 chickens
      always had access to perches during their life cycle. At 71 wk of age, chickens
      were sampled for measurement of plasma catecholamines (epinephrine,
      norepinephrine, and dopamine) and corticosterone; blood serotonin and Trp;
      fluctuating asymmetry of shank length and width; and adrenal weight. Only shank
      width differed among treatments. Chickens with previous exposure to perches
      during the pullet phase had wider shanks than chickens without access to perches
      (P = 0.006), suggesting that early perching promoted skeletal development. These
      results suggest that a stress response was not elicited in 71-wk-old White
      Leghorn hens that always had access to perches compared with hens that never had
      access to perches during all or part of their life cycle. 

PMID- 24879682
TI  - Performance of an animal-based test of thirst in commercial broiler chicken
      farms.
AB  - Animal-based measures of thirst are currently absent from animal welfare
      monitoring schemes due to the lack of a well-validated indicator applicable for
      on-farm use. In the present study, an on-farm test based on voluntary water
      consumption from an unfamiliar open drinker was validated in a (semi-)commercial
      setting. To investigate the effect of thirst on water consumption, we subjected 4
      flocks of 1,500 broilers to either 0 or 12 h of water deprivation and
      subsequently measured the amount of water that small subgroups consumed after the
      deprivation period (first experiment). Broilers that were water deprived before
      the test drank more than control broilers (P < 0.001). In a second experiment, a
      similar test was performed using 20 commercial broiler flocks in Belgium and
      Brazil. After a pretreatment water consumption test, the birds were subjected to
      0 or 6 h of water deprivation, and a posttreatment water consumption test was
      conducted. Only in Brazil, deprived birds drank significantly more than controls
      in the posttreatment water consumption test (P < 0.001). A tendency for a
      difference was found in Belgium (P = 0.083). Pre- and posttreatment water
      consumption was higher in Brazil than in Belgium (P < 0.001). Stocking density
      and temperature influenced, respectively, the pretreatment and the control's
      posttreatment water consumption in Brazil, but not in Belgium. These results
      indicate that the water consumption test is sufficiently sensitive to
      discriminate between control and 12 h deprived flocks, and in Brazil even between
      control and 6 h deprived birds. The location of the test within the house did not
      affect the amount of water consumed in either experiment, suggesting that this
      variable does not have to be standardized. However, the amount of water consumed
      by broilers able to drink freely for a long period depended on indoor climatic
      variables (in Brazil only) and possibly genotype. This suggests that these
      variables need to be considered when interpreting the test outcome in terms of
      the thirst level experienced by the broilers. 

PMID- 24879683
TI  - Housing system influences abundance of Pax3 and Pax7 in postnatal chicken
      skeletal muscles.
AB  - Paired box (Pax) proteins 3 and 7 are associated with activation of muscle
      satellite cells and play a major role in hyperplastic and hypertrophic growth in
      postnatal skeletal muscle fibers. The objective of this study was to evaluate the
      effect of housing system on abundance of Pax3 and Pax7 in postnatal chicken
      skeletal muscles. At 42 d, 1,200 chickens with similar BW were randomly assigned
      to cage, pen, and free-range group. The mRNA abundance was measured in pectoralis
      major and thigh muscle at d 56, 70, and 84, and the protein expression was
      quantified at d 84. Increases in mRNA abundance of PAX3 and PAX7 with age were
      less pronounced in caged system chickens than in pen and free-range chickens from
      d 56 to 84, and free-range chickens showed a more pronounced increase in gene
      expression with age compared with penned chickens. At d 84, quantities of PAX3
      and PAX7 mRNA and protein were highest in both pectoralis major and thigh muscle
      of chickens raised in the free-range group, lowest in penned chickens, and
      intermediate in caged chickens (P < 0.05). These data indicate that housing
      system may influence muscle fiber muscle accretion by coordinating the expression
      of Pax3 and Pax7 in adult chicken skeletal muscles. 

PMID- 24879684
TI  - Effects of long-term heat stress in an experimental model of avian necrotic
      enteritis.
AB  - Stressful conditions are predisposing factors for disease development. Heat
      stress is one of the most important stressors in poultry production. The
      reemergence of some previously controlled diseases [e.g., avian necrotic
      enteritis (NE)] has been extensively reported. The combination of bacterial
      infection and certain environmental factors have been reported to trigger the
      disease. The aim of this study was to analyze the effects of long-term heat
      stress (35 +/- 1 degrees C) on the development of NE in broiler chickens. For
      this purpose, 60 male broiler chickens were divided into the following 6 groups:
      control group (C), heat stressed control group (C/HS35), thioglycolate group (T),
      thioglycolate heat-stressed group (T/HS35), infected group (I), and infected heat
      stressed group (I/HS35). The poultry of groups I and I/HS35 were experimentally
      infected with Clostridium perfringens via their feed from 15 to 21 d of life.
      Heat stress (35 +/- 1 degrees C) was constantly applied to the birds of the
      stressed groups from 14 to 21 d of life. The infected and heat-stressed broiler
      chickens presented a trend toward a decrease in gross lesion scores and
      significantly lower microscopic scores of necrosis in the duodenum and jejunum (P
      < 0.05), lower fusion of villi in the duodenum (P < 0.05), and lower congestion
      scores in the jejunum and ileum (P < 0.05) in relation to infected and non-heat
      stressed chickens. Broilers of I/HS35 group also exhibited small number of
      heterophils in the duodenum and jejunum compared with those of the I group (P <
      0.05). Furthermore, the duodenum and jejunum of infected and heat-stressed
      broilers showed lower number of clostridia on the intestinal mucosa (P < 0.05).
      Data were discussed in light of a heat stress induced reduction on intestinal
      inflammation via a decrease in heterophil migration to the intestinal mucosa,
      which in turn might have reduced tissue damage during inflammation, hence
      preventing the development of a more severe form of NE. 

PMID- 24879685
TI  - Evaluating portable wire-flooring models for inducing bacterial chondronecrosis
      with osteomyelitis in broilers.
AB  - Rearing broilers on flat or sloping wire flooring is an effective method for
      consistently triggering lameness attributable to bacterial chondronecrosis with
      osteomyelitis (BCO). Portable obstacles known as speed bumps (SB) also
      consistently trigger modest incidences of BCO when they are installed between
      feed and water lines in litter flooring facilities. Two experiments were
      conducted to determine the most effective broiler age for introducing the SB into
      litter flooring pens, and to evaluate alternative configurations of the
      traditional SB with the expectation that amplified mechanical challenges to the
      legs of broilers should increase the incidence of BCO. Broiler chicks obtained
      from commercial hatcheries (lines B and D in experiment 1, lines A and B in
      experiment 2) were reared in floor pens with ad libitum feed and water and a
      23L:1D photoperiod. In experiment 1, the 5 floor treatments included wood
      shavings litter only (L), flat wire only (W), or litter plus SB installed at 14,
      28, or 42 d of age. Line B was more susceptible to lameness than line D (25.9 vs.
      15.3% for all treatments combined; P = 0.001). Both lines developed low
      incidences of lameness on L (11 to 13%), intermediate incidences on SB regardless
      of day of installation (12 to 23%), and high incidences on W (21 to 39%). In
      experiment 2, broilers were reared with 7 floor treatments, including L, W, SB
      with a 50% slope (SB50%); SB50% with a limbo bar installed over the apex; SB with
      a 66% slope and limbo bar; SB50% with a nipple water line suspended over the
      apex; and a pagoda-top SB. All SB were inserted on d 28. Line B was more
      susceptible to lameness than line A (20.2 vs. 16.1% for all treatments combined;
      P < 0.05), and for both lines combined the lameness percentages averaged 7.7 (L),
      29.2 (W), 17.3 (SB50%), 16.2 (SB50% with a limbo bar), 21.5 (SB with a 66% slope
      and limbo bar), 20.8 (SB50% with a nipple water line), and 11.5% (pagoda-top).
      These studies demonstrate the portable SB can be effectively used to
      experimentally trigger BCO in broilers. 

PMID- 24879687
TI  - Inhibition of growth and alteration of host cell interactions of Pasteurella
      multocida with natural byproducts.
AB  - Pasteurella multocida is a leading cause of fowl cholera in both free-range
      pasture and conventional/commercially raised poultry. Its infection is a serious
      threat to poultry health and overall flock viability. Organic poultry is
      comparatively more vulnerable to this pathogen. It is a significant cause of
      production loss and price increase of poultry products, specifically organic
      poultry products. Some plant products are well documented as sources of natural
      antimicrobials such as polyphenols found in different berry pomaces and citrus
      oil. Pomace, a byproduct (primarily of seeds and skins) of fruits used for juice
      and wine production, and citrus oil, the byproduct of citrus juice production,
      show promising antimicrobial activity against various pathogens. Here, we showed
      for the first time that blackberry and blueberry pomace extracts and citrus oil
      inhibited P. multocida growth. Minimum bactericidal concentrations were
      determined as 0.3 and 0.4 mg/mL gallic acid equivalent for blackberry and
      blueberry pomace extracts, respectively. Similarly, only 0.05% citrus oil
      (vol/vol) completely inhibited P. multocida growth. Under shaking conditions, the
      antimicrobial activity of both pomace extracts and citrus oil was more intensive.
      Even citrus oil vapor also significantly reduced the growth of P. multocida. In
      addition, cell surface hydrophobicity of P. multocida was increased by 2- to 3
      fold and its adherence to chicken fibroblast (DF1) and bovine mammary gland
      (MacT) cells was reduced significantly in the presence of pomace extracts only.
      This study indicates that these natural products might be good alternatives to
      conventional antimicrobial agents, and hence, may be used as feed or water
      supplements to control fowl cholera and reduce production loss caused by P.
      multocida. 

PMID- 24879686
TI  - Rosiglitazone modulates pigeon atherosclerotic lipid accumulation and gene
      expression in vitro.
AB  - Atherosclerosis is a major contributor to the overall United States mortality
      rate, primarily in the form of heart attacks and stroke. Unlike the human
      disease, which is believed to be multifactorial, pigeon atherosclerosis is due to
      a single gene autosomal recessive trait. The White Carneau (WC-As) strain
      develops atherosclerotic plaques without the presence of known environmental risk
      factors such as diet and classic predictors such as blood pressure or blood
      cholesterol levels. With similar parameters, the Show Racer (SR-Ar) is resistant
      to plaque development. Thiazolidinediones, including rosiglitazone, activate the
      peroxisome proliferator-activated receptor gamma (PPARgamma) raising cellular
      sensitivity to insulin. The effect of rosiglitazone was evaluated in aortic
      smooth muscle cells (SMC) from these 2 pigeon breeds. Primary SMC cultures were
      prepared from WC-As and SR-Ar squabs. Cell monolayers, which achieved confluence
      in 7 d, were treated with 0 or 4 uM rosiglitazone for 24 h. Cellular lipid
      accumulation was evaluated by oil red O staining. Control WC-As cells had
      significantly higher vacuole scores and lipid content than did the SR-Ar control
      cells. Rosiglitazone treatment decreased WC-As lipid vacuoles significantly
      compared with the control cells. On the other hand, lipid vacuoles in the treated
      and untreated SR-Ar cells did not differ significantly. The effect of
      rosiglitazone on WC-As SMC gene expression was compared with control SMC using
      representational difference analysis. Significant transcript increases were found
      for caveolin and RNA binding motif in the control cells compared with the
      rosiglitazone-treated cells as well as cytochrome p450 family 17 subfamily A
      polypeptide 1 (CYP171A) in the rosiglitazone-treated cells compared with the
      control cells. Although rosiglitazone was selected for these experiments because
      of its role as a PPARgamma agonist, it appears that the drug also tempers c-myc
      expression, as genes related to this second transcription factor were
      differentially expressed. Both PPARgamma and c-myc appear to affect WC-As SMC
      gene expression, which may relate to disease development, progression, or both. 

PMID- 24879688
TI  - Differential regulation of microRNA transcriptome in chicken lines resistant and
      susceptible to necrotic enteritis disease.
AB  - Necrotic enteritis (NE) is a re-emerging disease as a result of increased
      restriction on the use of antibiotics in poultry. However, the molecular
      mechanisms underlying the pathogenesis of NE are unclear. Small RNA transcriptome
      analysis was performed using spleen and intestinal intraepithelial lymphocytes
      (IEL) from 2 inbred chicken lines selected for resistance or susceptibility to
      Marek's disease (MD) in an experimentally induced model of avian NE to
      investigate whether microRNA (miRNA) control the expression of genes associated
      with host response to pathogen challenge. Unique miRNA represented only 0.02 to
      0.04% of the total number of sequences obtained, of which 544 were unambiguously
      identified. Hierarchical clustering revealed that most of miRNA in IEL were
      highly expressed in the MD-susceptible line 7.2 compared with MD-resistant line
      6.3. Reduced CXCL14 gene expression was correlated with differential expression
      of several unique miRNA in MD-resistant chickens, whereas TGFbetaR2 gene
      expression was correlated with altered gga-miR-216 miRNA levels in MD-susceptible
      animals. In conclusion, miRNA profiling and deep sequencing of small RNA in
      experimental models of infectious diseases may be useful for further
      understanding of host-pathogen interactions, and for providing insights into
      genetic markers of disease resistance. 

PMID- 24879689
TI  - Effects of Mycoplasma gallisepticum vaccination on serum alpha1-acid glycoprotein
      concentrations in commercial layer chickens.
AB  - Increases in circulating acute phase protein (APP) levels occur in reaction to
      systemic infections in animals. However, no previous research has been conducted
      to monitor possible changes in APP levels of birds in response to prelay
      vaccinations of various live attenuated Mycoplasma gallisepticum vaccines in
      conjunction with their subsequent use as an overlay vaccine during the production
      period. Serum concentrations of the APP, alpha1-acid glycoprotein (AGP), were
      determined on d 0, 1, 3, 7, 14, and 28 after subjecting commercial laying hens to
      one of the following treatments at 10 wk of age (woa): 1) control (no
      vaccination); 2) ts-11 strain M. gallisepticum (ts11MG) vaccination; 3) M.
      gallisepticum-bacterin (MGBac) vaccination; and 4) ts11MG and MGBac combination
      (ts11MG & MGBac) vaccination. Furthermore, at 45 woa, the birds in half of the
      units assigned to each treatment group were vaccinated with high-passage F-strain
      M. gallisepticum (HpFMG). Birds in treatment 1 that were (single control) and
      were not (double control) vaccinated with HpFMG, and birds in treatments 2, 3,
      and 4 that were vaccinated with HpFMG were further tested during lay on d 0, 1,
      3, 7, 14, and 28 after vaccination. On d 7, 14, and 28 postvaccination at 10 woa,
      the ts11MG & MGBac, ts11MG, and MGBac group AGP concentrations were not different
      from one another, but all were higher than those in the control group. Similarly,
      on d 3, 7, and 14 postvaccination, the single control, and the MGBac ts11MG, and
      ts11MG & MGBac treatment groups that were later vaccinated with HpFMG at 45 woa,
      were not different, but all were higher than that in the double control group. In
      conclusion, elevated circulation AGP concentrations may be used to detect and
      confirm subclinical infections in pullets up to 28 d after having been vaccinated
      with ts11MG, MGBac, or their combination. Furthermore, in association with
      depressed performance, elevated serum AGP concentrations in layers may be used to
      confirm HpFMG infections up to 28 d after its use as a vaccine. 

PMID- 24879690
TI  - Effects of live and killed vaccines against Mycoplasma gallisepticum on the
      performance characteristics of commercial layer chickens.
AB  - Different vaccine strains of Mycoplasma gallisepticum have been used on multiple
      age commercial layer farms in an effort to protect birds against virulent field
      strain infections. Use of the F-strain of M. gallisepticum (FMG), as an overlay
      vaccine during lay, may be necessary because of the lower level of protection
      afforded by M. gallisepticum vaccines of low virulence given before lay. Two
      replicate trials were conducted to investigate effects of live and killed M.
      gallisepticum vaccines administered individually and in combination before lay,
      in conjunction with an FMG vaccine overlay after peak egg production (EP), on the
      performance characteristics of commercial layers. The following treatments were
      utilized at 10 wk of age (woa): 1) control (no vaccinations); 2) ts11 strain M.
      gallisepticum (ts11MG) vaccine; 3) M. gallisepticum-Bacterin vaccine (MG
      Bacterin); and 4) ts11MG and MG-Bacterin vaccines combination. At 45 woa, half of
      the birds were overlaid with an FMG vaccine. Hen mortality, BW, egg weight,
      percentage hen-day EP, egg blood spots, and egg meat spots were determined at
      various time periods between 18 and 52 woa. The data from each trial were pooled.
      Treatment did not affect performance in interval I (23 to 45 woa). However,
      during interval II (46 to 52 woa), the EP of control and MG-Bacterin-vaccinated
      birds that later received an FMG vaccine overlay was lower than that in the other
      treatment groups. Furthermore, treatment application reduced bird BW during
      interval II. Despite the effects on BW and EP, no differences were observed for
      egg blood or meat spots among the various treatments. It is suggested that the
      vaccination of commercial layers before lay with ts11MG, but not MG-Bacterin, may
      reduce the negative impacts of an FMG overlay vaccination given during lay. These
      results establish that the vaccination of pullets with ts11MG in combination with
      the vaccination of hens with an FMG overlay, for continual protection against
      field-strain M. gallisepticum infections, may be used without suppressing
      performance. 

PMID- 24879691
TI  - Using a computer-controlled simulated digestion system to predict the energetic
      value of corn for ducks.
AB  - Two experiments were conducted to develop a computer-controlled digestion system
      to simulate the digestion process of duck for predicting the concentration of ME
      and the metabolizability of gross energy (GE) in corn. In a calibration
      experiment, 30 corn-based calibration samples with a previously published ME
      concentration in 2008 were used to develop the prediction models for in vivo
      energetic values. The linear relationships were established between in vivo ME
      concentration and in vitro digestible energy (IVDE) concentration, and between in
      vivo metabolizability of GE (ME/GE) and in vitro digestibility of GE (IVDE/GE),
      respectively. In a validation experiment, 6 sources of corn with previously
      published ME concentration in 2008 randomly selected from the primary corn
      growing regions of China were used to validate the prediction models established
      in the calibration experiment. The results showed that in calibration samples,
      the IVDE concentration was positively correlated with the AME (r = 0.9419), AMEn
      (r = 0.9480), TME (r = 0.9403), and TMEn concentration (r = 0.9473). Similarly,
      the IVDE/GE was positively correlated with the AME/GE (r = 0.95987), AMEn/GE (r =
      0.9641), TME/GE (r = 0.9588), and TMEn/GE (r = 0.9637). The coefficient of
      determination greater than 0.88 and 0.91, and residual SD less than 45 kcal/kg of
      DM and 1.01% were observed in the prediction models for ME concentrations and
      ME/GE, respectively. Twenty-nine out of 30 calibration samples showed differences
      less than 100 kcal/kg of DM and 2.4% between determined and predicted values for
      4 ME (AME, AMEn, TME, and TMEn) and for 4 ME/GE (AME/GE, AMEn/GE, TME/GE, and
      TMEn/GE), respectively. Using prediction models developed from 30 calibration
      samples, 6 validation samples further showed differences less than 100 kcal/kg of
      DM and 2% between determined and predicted values for ME and ME/GE, respectively.
      Therefore, the computer-controlled simulated digestion system can be used to
      predict the ME and ME/GE of corn for ducks with acceptable accuracy. 

PMID- 24879692
TI  - Evaluation of feeding various sources of distillers dried grains with solubles in
      non-feed-withdrawal molt programs for laying hens.
AB  - An experiment was conducted using 588 Hy-Line W-36 hens (68 wk of age) to
      evaluate if laying hens can be successfully molted by ad libitum feeding various
      levels of 3 sources of distillers dried grains with solubles (DDGS). Treatment 1
      consisted of a 47% corn (C):47% soy hulls (SH) molt diet (C:SH) fed for 28 d
      (positive control). Treatments 2, 3, and 4 were molt diets containing 94% DDGS
      from the 3 sources fed for 28 d. Treatments 5, 6, and 7 were 32% C: 42% SH: 20%
      DDGS, from each of the 3 DDGS sources, also fed for 28 d. At the end of the 28-d
      molt period, all hens were fed a 16% CP corn-soybean meal layer diet. Body weight
      loss during the molt period was significantly greater (P < 0.05) for hens fed the
      C:SH diet (26%) than hens fed the diets containing DDGS, and the reduction in BW
      loss varied among DDGS sources. Feed intake was lower (P < 0.05) for the C:SH
      control treatment compared with most DDGS treatments. Hens fed the C:SH diet had
      egg production near 0% during the last 3 wk of the molt period. Hens on the other
      treatments did not have mean egg production below 17% during the molt period (wk
      1 to 4), and the reduction in egg production varied among DDGS sources. Postmolt
      hen-day egg production (5-41 wk) did not significantly differ among treatments;
      however, egg mass and egg specific gravity were generally reduced (P < 0.05) for
      hens fed the 94% DDGS molt diets compared with hens fed the C:SH diet. This study
      showed that molt and postmolt performance responses varied among DDGS sources;
      however, none of the molt diets containing 20 to 94% DDGS yielded molt period
      reductions in BW or egg production similar to a 47% C: 47% SH diet. 

PMID- 24879693
TI  - Validation of prediction equations for apparent metabolizable energy of corn
      distillers dried grains with solubles in broiler chicks.
AB  - An experiment consisting of 3 nearly identical trials was conducted to determine
      the AMEn content of distillers dried grains with solubles (DDGS) to validate 4
      previously published prediction equations for AMEn of corn DDGS in broilers. In
      addition, prior research data were used to generate a best-fit equation for AMEn
      based on proximate analysis. Fifteen samples of DDGS ranging in ether extract
      (EE) from 4.98 to 14.29% (DM basis) were collected from various dry-grind ethanol
      plants and were subsequently fed to broiler chicks to determine AMEn content. A
      corn-soybean meal control diet was formulated to contain 15% dextrose and test
      diets were created by mixing the control diet with 15% DDGS at the expense of
      dextrose. In each trial, male Ross * Ross 708 chicks were housed in grower
      battery cages and received a common starter diet until the experimental period.
      Each cage was randomly assigned to 1 of the dietary treatments (trial 1 and trial
      2: control + 6 test diets, 13 replicates per diet; trial 3: control + 3 test
      diets, 12 replicates per diet). Experimental diets were fed over a 6-d
      acclimation period, followed by a 48-h total excreta collection period. On a DM
      basis, AMEn of the 15 DDGS samples ranged from 1,975 to 3,634 kcal/kg. Analyses
      were conducted to determine gross energy, CP, EE, DM, starch, total dietary
      fiber, neutral detergent fiber, crude fiber (CF), acid detergent fiber, and ash
      content of the DDGS samples. All results were reported on a DM basis. Application
      of the 4 equations to the validation data resulted in root mean square error
      (RMSE) values of 335, 381, 488, and 502 kcal/kg, respectively. Least absolute
      shrinkage and selection operator technique was applied to proximate analysis data
      for 30 corn coproducts adapted from prior research and resulted in the following
      best-fit equation: [AMEn (kcal/kg) = 3,673 - (121.35 * CF) + (51.29 * EE) -
      (121.08 * ash); P < 0.01; R(2) = 0.70; R(2) adj = 0.67; RMSE = 270 kcal/kg]. The
      RMSE values obtained through validation were not consistent with the expectation
      of predictive performance based on internal measures of fit for each equation.
      These results indicated that validation is necessary to quantify the expected
      error associated with practical application of each individual prediction
      equation to external data. 

PMID- 24879694
TI  - The effects of different thermal treatments and organic acid levels in feed on
      microbial composition and activity in gastrointestinal tract of broilers.
AB  - Thermal treatments of feed and organic acids are known to affect the
      gastrointestinal microbiota in chickens. The present study evaluated the effect
      of different thermal processes including pelleting (P), long-term conditioning at
      85 degrees C for 3 min (L), expanding at 110 degrees C (E110), and 130 degrees C
      for 3 to 5 s (E130) as well as organic acid (63.75% formic acid, 25.00% propionic
      acid, and 11.25% water) inclusion levels (0, 0.75, and 1.5%) on gastrointestinal
      microbiota in broilers. In total, 960 one-day-old chicks were randomly assigned
      to 8 replicates using a 3 * 4 factorial arrangement. At d 35, bacterial cell
      numbers in the crop, ileum, and cecum, and bacterial metabolites in the crop,
      gizzard, ileum, and cecum were determined. The inclusion of 1.5% organic acids
      increased cell numbers of all clostridial clusters in the crop. The organic acid
      supplementation increased the propionic acid concentration in the crop and
      gizzard and there was a decrease in lactic acid concentration. In the ileum, the
      0% organic acid group had the highest numbers of Lactobacillus spp. and
      enterobacteria. Inclusion of 1.5% organic acids increased ileal acetate
      concentration. Increasing the feed processing temperature led to an increase of
      lactobacilli in the crop and ileum, whereas clostridia and enterobacteria seemed
      unaffected. Similarly, lactate concentrations increased in the ileum, but short
      chain fatty acids remained identical. In the crop, an increase for acetate was
      found for the E130 group compared with all other thermal treatments. In
      conclusion, our study demonstrated that thermal treatments and organic acid
      supplementation to broiler diets more markedly influenced the bacterial status of
      the crop compared with the downstream segments and their effects decreased along
      the length of gastrointestinal tract. Whereas organic acids markedly modified
      bacterial composition and activity in the crop, expansion increased lactobacilli
      and lactate in the crop and ileum. 

PMID- 24879695
TI  - Influence of tallow and calcium concentrations on the performance and energy and
      nutrient utilization in broiler starters.
AB  - The influence of tallow and Ca concentrations on the performance, apparent ileal
      digestibility, and total tract retention of N, Ca, P, and AME in broiler starter
      diets fed corn-soy-based diets was examined. The experimental design was a 3 * 3
      factorial arrangement of treatments evaluating 3 inclusion levels of tallow (0,
      40, and 80 g/kg) and 3 dietary concentrations of Ca (7, 10, and 13 g/kg). Nine
      treatment diets were formulated to meet the requirements for major nutrients for
      broiler starters, except for AME and Ca concentrations. The results showed that
      increasing tallow inclusion increased (P < 0.001) the weight gain and lowered (P
      < 0.001) the feed to gain. Increasing dietary Ca concentrations decreased (P <
      0.001) the weight gain. Birds fed diets containing 7 g/kg of Ca had similar (P >
      0.05) feed to gain to 10 g/kg of Ca but lower (P < 0.05) than that of 13 g/kg of
      Ca. In diets with no tallow, increasing Ca concentrations decreased (P < 0.05)
      feed intake, whereas diets with 40 and 80 g/kg of tallow containing 13 g/kg of Ca
      showed lower (P < 0.05) feed intake than those of 7 and 10 g/kg of Ca. Diets
      supplemented with 40 and 80 g/kg of tallow containing 7 g/kg of Ca showed the
      lowest (P < 0.05) excreta soap content. Total tract retention of fat was higher
      (P < 0.001) in diets with 40 g/kg of tallow compared with those with 0 and 80
      g/kg of tallow. Birds fed diets containing 7 g/kg of Ca had similar (P > 0.05)
      fat retention to that of 10 g/kg of Ca, but higher (P < 0.05) than that of 13
      g/kg of Ca. Calcium retention decreased (P < 0.001) with increasing Ca
      concentrations. Diets containing 13 g/kg of Ca had the lowest (P < 0.01) P
      retention. Diets with no inclusion of tallow containing 7 g/kg of Ca had higher
      (P < 0.05) N retention than that of 13 g/kg of Ca, but similar to 10 g/kg of Ca,
      whereas in 40 g/kg of tallow diets, 7 g/kg of Ca had the highest (P < 0.05) N
      retention. Increasing fat inclusion increased (P < 0.001) the soap content in
      ileal digesta. Diets with 40 g/kg of tallow had the highest ileal digestibility
      of fat (P < 0.001) and N (P < 0.01). Increasing inclusion of fat decreased (P <
      0.001) ileal Ca digestibility. Diets containing 7 g/kg of Ca showed the highest
      ileal digestibility of fat (P < 0.01), N (P < 0.01), and P (P < 0.001). Birds fed
      diets containing 13 g/kg of Ca had higher ileal digestibility of Ca (P < 0.001)
      than those fed 7 and 10 g/kg of Ca diets. Overall, present data showed that the
      total tract retention and ileal digestibility of fat were higher with
      supplementation of 40 g/kg of tallow compared with those of 0 and 80 g/kg of
      tallow. High dietary Ca concentrations adversely affected the performance and the
      utilization of energy, N, Ca, and P in broiler starters. 

PMID- 24879696
TI  - Effects of protein source and nutrient density in the diets of male broilers from
      8 to 21 days of age on their subsequent growth, blood constituents, and carcass
      compositions.
AB  - The effects of protein source and amino acid (AA) and AME levels in the diets of
      male broilers from 8 to 21 d of age on subsequent growth and blood and carcass
      traits were investigated in the current study. Fourteen Ross * Ross 708 male
      broiler chicks were randomly allocated to each of 80 floor pens arranged in a
      randomized complete block design. Each diet contained 1 of 2 dietary protein
      sources (high inclusion of distillers dried grains with solubles or high
      inclusion of meat and bone meal), 1 of 2 AA densities (moderate or 10% higher),
      and 1 of 2 AME densities (2,998 or 3,100 kcal/kg). Experimental diets were fed
      from 8 to 21 d of age, and common diets from 1 to 7 and 21 to 55 d of age. The
      higher AME density in high inclusion of meat and bone meal diets increased serum
      triglyceride and cholesterol levels on d 20. The dietary inclusion of high
      inclusion of distillers dried grains with solubles or lower levels of AA
      increased high-density lipoprotein cholesterol on d 20. Feeding the high-AA
      density diet decreased feed intake without affecting BW gain, which resulted in a
      lower feed conversion ratio (FCR). A high-AME-density diet lowered feed intake
      but increased BW gain, which resulted in a lower FCR from 8 to 21 d of age. Feed
      intake, BW gain, FCR from 21 to 54 d of age, and carcass weight on 42 and 55 d of
      age were not affected by treatments from 8 to 21 d of age. However, early dietary
      manipulation from 8 to 21 d of age affected fat and meat yield at 42 and 55 d of
      age. Moreover, a high-AME diet decreased feed cost per carcass weight gain from 8
      to 55 d of age. In conclusion, high AA or AME densities during the grower phase,
      from d 8 to 21 of age, may improve growth during the grower feeding phase, but
      may also affect meat yield during the latter grow-out phases. Furthermore, high
      AME diets from 8 to 21 d of age may save on feed costs for meat production. 

PMID- 24879697
TI  - Dietary taurine impairs intestinal growth and mucosal structure of broiler
      chickens by increasing toxic bile acid concentrations in the intestine.
AB  - Three experiments were conducted to determine the effect of taurine on the
      intestinal development, bile acid concentrations, and hormonal status of
      chickens. In experiment 1, a total of 250 one-day-old broilers were randomly
      allocated to 5 treatments and supplemented with 0, 0.25, 0.50, 1.00, and 2.00
      g/kg of taurine, respectively. Growth performance, weight and length of the small
      intestine, and intestinal morphology were measured on d 7, 22, and 44. The gene
      expression levels of several hormones, including epidermal growth factor and
      cholecystokinin, were also evaluated. In experiment 2, 60 one-day-old broilers
      were supplemented with 0, 1.0, and 5.0 g/kg of taurine to assess cell
      proliferation in the jenunal crypt. In experiment 3, 100 newly hatched broilers
      were assigned randomly to 5 treatments (0, 0.10, 0.50, 2.00, 8.00 g/kg of
      taurine) to evaluate the bile acid concentrations in the jejunal mucosa. Our
      results indicated that dietary taurine decreased the length and weight of small
      intestine, the villus width, surface area, and crypt depth in the duodenum and
      jejunum (P < 0.05). Taurine also increased the expression of cholecystokinin and
      epidermal growth factor on the jejunal mucosa (P < 0.001). Taurine has little
      effect on stimulating the proliferation of intestinal crypt cells, except for 5
      g/kg of taurine supplementation on d 14 (P < 0.05). Additionally, a linear
      increase in the jejunal concentrations of taurocholic acid, taurochenodeoxycholic
      acid, and taurolithocholic acid was observed on d 7 in broilers fed increasing
      levels of taurine. In conclusion, we suggested that taurine impairs intestinal
      mucosal development partly through generation of toxic bile acids. 

PMID- 24879698
TI  - Effect of the timing of posthatch feed restrictions on broiler breast muscle
      development and muscle transcriptional regulatory factor gene expression.
AB  - The effect of the timing of an immediate posthatch feed restriction on broiler
      pectoralis major muscle development was studied by applying a 20% feed
      restriction either the first or second week after hatch. Pectoralis major muscle
      morphological structure and the expression of the myogenic transcriptional
      regulatory factors, myogenic determination factor 1 (MyoD), myogenic regulatory
      factor 4 (MRF4), and myogenin, were measured. Broiler chicks at hatch were
      divided into a full-fed (control) group and a 20% feed restriction treatment
      administered either the first or second week posthatch. At the end of the feed
      restriction, the chicks were placed on a full feed ad libitum diet with no
      further restrictions. Muscle fiber diameter and fiber bundle size of the
      pectoralis major muscle were smaller in the wk 1 restricted group than the
      control group by 7 d of age. By 15 d of age through the duration of the study, d
      43, both endomysial and perimysial connective tissue spacing were diminished in
      the wk 1 feed-restricted group. The expression of MyoD, MRF4, and myogenin was
      affected by the wk 1 feed restriction. The expression of MyoD and MRF4 was
      significantly increased during the first week posthatch. Both of the genes have
      been shown to be expressed during proliferation especially MyoD, which is
      required for muscle cell proliferation. In contrast, myogenin expression was
      significantly decreased. Myogenin expression is required for differentiation to
      occur. The morphological changes and gene expression changes observed with the wk
      1 feed restriction were eliminated by moving the 20% feed restriction to wk 2,
      which is after the period of maximal myogenic satellite cell mitotic activity.
      Taken together, these results demonstrate that the timing of early posthatch feed
      restrictions to chicks is critical for the morphological development of the
      pectoralis major muscle and the expression of genes required for muscle satellite
      cell proliferation and differentiation. 

PMID- 24879699
TI  - Isolation and characterization of chicken bile matrix metalloproteinase.
AB  - Avian bile is rich in matrix metalloproteinases (MMP), the enzymes that cleave
      extracellular matrix proteins such as collagens and proteoglycans. Changes in
      bile MMP expression have been correlated with hepatic and gall bladder
      pathologies, but the significance of their expression in normal, healthy bile is
      not understood. We hypothesized that the MMP in bile may aid the digestion of
      native collagens that are resistant to conventional gastric proteases. Hence, the
      objective of this study was to characterize the bile MMP and check its regulation
      in association with dietary factors. We used substrate zymography, azocoll
      protease assay, and gelatin affinity chromatography to identify and purify the
      MMP from chicken bile. Using zymography and SDS PAGE, 5 bands at 70, 64, 58, 50,
      and 42 kDa were detected. The bands corresponding to 64, 50, and 42 kDa were
      identified as MMP2 using trypsin in-gel digestion and matrix-assisted laser
      desorption time-of-flight mass spectrometry and peptide mass fingerprinting.
      Chickens fed diets containing gelatin supplements showed higher levels of MMP
      expression in the bile by both azocoll assay and zymography. We conclude that the
      bile MMP may be associated with the digestion of collagens and other
      extracellular matrix proteins in avian diets. 

PMID- 24879701
TI  - Comparison of meat quality characteristics and oxidative stability between
      conventional and free-range chickens.
AB  - The aim of this research was to evaluate quality traits and oxidative stability
      of meat products from free-range (FR) and conventionally (C) raised chickens as
      they actually reach consumers in the Italian retail market. Free-range female and
      male chickens (n = 1,500 + 1,500), medium growing ISA strain, were raised under
      commercial conditions for 56 (1.8 kg of live weight) and 70 d (3.1 kg of live
      weight), respectively; C female and male birds (n = 5,000 + 5,000) were a fast
      growing hybrid (Ross 708) and were separately raised for 39 (1.9 kg of live
      weight) and 50 d (3.1 kg of live weight), respectively. A total of 96 chickens
      (equally divided by production system and sex) were slaughtered in 2 separate
      sessions to obtain the main 2 commercial categories (rotisserie and cut-up,
      respectively). After slaughtering, 12 carcasses of each treatment group were
      randomly selected and used to assess quality properties, chemical composition,
      and oxidation stability of breast and leg meat. The C birds had dramatic higher
      carcass and breast meat yield, whereas FR had higher wing and leg yields. The FR
      birds exhibited higher water holding capacity in both breast and leg meat.
      Although shear force did not differ in breast meat, legs from FR birds were
      tougher. Fatty acid composition of FR breast and thigh meat of both categories
      were characterized by a higher polyunsaturated fatty acid n-6-/n-3 ratio. In
      general, a low lipid oxidation level (peroxide value < 1.3 mEq O2/kg of lipid and
      TBA reactive substances < 0.2 mg malondialdehyde/kg of sample) was found in
      breast and legs, regardless of the commercial category. However, the C system
      significantly increased peroxide value in rotisserie thigh meat, whereas FR led
      to a significantly higher TBA reactive substances in breast meat. Our results
      demonstrated that free range can modify the properties of chicken meat and also
      highlighted the importance of the bird genetic background to select nutritional
      strategies to improve meat quality traits and oxidative stability in poultry. 

PMID- 24879700
TI  - Combined effects of chlorine and thiamine dilauryl sulfate on reduction of
      Listeria monocytogenes in chicken breast and development of predictive growth
      models.
AB  - The inhibitory effect of chlorine (50, 100, and 200 mL/kg) and thiamine dilauryl
      sulfate (TDS: 100, 500, and 1,000 mg/kg) on Listeria monocytogenes in chicken
      breast was investigated. Also, predictive growth models as a function of chlorine
      and TDS concentration, and storage temperature (4, 10, and 15 degrees C) were
      developed using a polynomial model. Listeria monocytogenes counts were
      significantly (P < 0.05) different in samples treated with sterile distilled
      water and combinations of chlorine and TDS. The maximum reduction effect was 0.5
      log cfu/g by combined treatment of 200 mL/kg chlorine and 1,000 mg/kg TDS. The
      largest synergistic effect was 0.38 log cfu/g by combined treatment of 100 mL/kg
      chlorine and 1,000 mg/kg TDS. The primary models that were developed to obtain
      the specific growth rates (SGR) and lag time (LT) had good fitness (R(2) > 0.91)
      determined by the reparameterized Gompertz equation. The secondary polynomial
      models were calculated by nonlinear regression analysis. In the validation of the
      developed models, the bias factor (Bf) and accuracy factor (Af) for SGR were 0.54
      and 1.84, respectively, whereas those for LT were 0.97 and 1.04, respectively. In
      quality analysis, chlorine and TDS did not change the color or texture of chicken
      breast meat during storage at 4 degrees C for 7 d. Thus, our findings indicate
      that a combined treatment of 100 mL/kg chlorine and 1,000 mg/kg TDS appears to an
      effective method into reduce L. monocytogenes in broiler carcasses with no
      negative effects on color and textural quality. The predictive models were in
      good agreement with the validation and may be used to predict L. monocytogenes
      growth in chicken breast. 

PMID- 24879702
TI  - Effects of access to pasture on performance, carcass composition, and meat
      quality in broilers: a meta-analysis.
AB  - Consumer preference for poultry meat from free-range birds is not justified by
      scientific evidence. Inconsistency in results among studies on the effects of
      access to pasture on performance, carcass composition, and meat quality has led
      to a meta-analysis to quantify effects. After identification of studies where
      response variables were directly compared between birds with and without access
      to pasture, standardized effect sizes were used to calculate differences. The
      effect size for growth combined according to a fixed effect model did not present
      heterogeneity (P = 0.116). However, with feed intake and feed efficiency,
      variability among studies (heterogeneity with P-values of below 0.10) was
      influenced by more than sampling error. Carcass yield was the only carcass
      component that showed heterogeneity (P = 0.008), whereas numerous response
      variables related to meat quality were not homogenous. The use of subgroup
      analysis and meta-regression to evaluate the sources of heterogeneity was limited
      by ill-defined explanatory variables and few values available within response
      variables. Consequently, between-study variability was accounted for by use of
      random effects models to combine effect sizes. According to these, few response
      variables were influenced by pasture access. Fat concentrations in breast (mean
      effect size = -0.500; 95% CI = -0.825 to -0.175; 11 studies; 14 comparisons),
      thigh (mean effect size = -0.908; 95% CI = -1.710 to -0.105; 4 studies; 5
      comparisons) and drum (mean effect size = -1.223; 95% CI = -2.210 to -0.237; 3
      studies; 3 comparisons) muscles were decreased in free-range birds. Access to
      pasture increased (P < 0.05) or tended to increase (P < 0.10) protein
      concentrations in the respective commercial cuts. It is concluded that factors
      other than enhanced meat quality could be responsible for consumer preference for
      meat from free-range poultry. 

PMID- 24879703
TI  - Impact of broiler processing scalding and chilling profiles on carcass and breast
      meat yield.
AB  - The effect of scalding and chilling procedures was evaluated on carcass and
      breast meat weight and yield in broilers. On 4 separate weeks (trials), broilers
      were subjected to feed withdrawal, weighed, and then stunned and bled in 4
      sequential batches (n = 16 broilers/batch, 64 broilers/trial). In addition,
      breast skin was collected before scalding, after scalding, and after defeathering
      for proximate analysis. Each batch of 16 carcasses was subjected to either hard
      (60.0 degrees C for 1.5 min) or soft (52.8 degrees C for 3 min) immersion
      scalding. Following defeathering and evisceration, 8 carcasses/batch were air
      chilled (0.5 degrees C, 120 min, 86% RH) and 8 carcasses/batch were immersion
      water-chilled (water and ice 0.5 degrees C, 40 min). Carcasses were reweighed
      individually following evisceration and following chilling. Breast meat was
      removed from the carcass and weighed within 4 h postmortem. There were
      significant (P < 0.05) differences among the trials for all weights and yields;
      however, postfeed withdrawal shackle weight and postscald-defeathered eviscerated
      weights did not differ between the scalding and chilling treatments. During air
      chilling all carcasses lost weight, resulting in postchill carcass yield of 73.0%
      for soft-scalded and 71.3% for hard-scalded carcasses, a difference of 1.7%.
      During water-chilling all carcasses gained weight, resulting in heavier postchill
      carcass weights (2,031 g) than for air-chilled carcasses (1,899 g). Postchill
      carcass yields were correspondingly higher for water-chilled carcasses, 78.2% for
      soft-scalded and 76.1% for hard-scalded carcasses, a difference of 2.1%. Only in
      trials 1 and 4 was breast meat yield significantly lower for hard-scalded, air
      chilled carcasses (16.1 and 17.5%) than the other treatments. Proximate analysis
      of skin sampled after scalding or defeathering did not differ significantly in
      moisture (P = 0.2530) or lipid (P = 0.6412) content compared with skin sampled
      before scalding. Skin protein content was significantly higher (P < 0.05) for
      prescald and soft-scalded skin samples than for hard-scalded or soft or hard
      scalded skin samples after defeathering. The hard-scalding method used in this
      experiment did not result in increased skin lipid loss either before or after
      defeathering. 

PMID- 24879704
TI  - Metabolomic study of fatty livers in ducks: Identification by 1H-NMR of metabolic
      markers associated with technological quality.
AB  - The control of fatty liver fat loss during cooking is a major issue. Previous
      studies showed that fat loss was influenced by bird production factors and liver
      technological treatments. However, part of the variability in fat loss remained
      uncontrolled. To provide enhanced insights into the determinism of fatty liver
      quality, liver hydrophilic metabolite profiles were measured by nuclear magnetic
      resonance of the proton ((1)H-NMR). The study aimed at i) comparing fatty livers
      with extreme fat loss values and ii) at characterizing the effect of postmortem
      evolution of livers during chilling. A group of 240 male mule ducks (Cairina
      moschata * Anas platyrhynchos) was reared and overfed. Their livers were sampled
      at 20 min and 6 h postmortem. Of these birds, 2 groups of ducks were built with
      extreme values on the technological yield (TY; TY = 100 - % fat loss; the low-fat
      loss group, TY = 89.9%, n = 13; and the high-fat-loss group, TY = 68.3%, n = 12,
      P < 0.001). The (1)H-NMR analyses showed that the high-fat-loss livers were more
      advanced in postmortem biochemical and structural changes than low-fat-loss
      livers early postmortem. The high-fat-loss livers were characterized by
      hydrolysis of glycogen into glucose, worse integrity of cell membrane with
      diminution of compounds of phospholipids, and higher catabolic processes. The
      accelerated postmortem processes may be the origin of the differences in fat loss
      during cooking. During the early postmortem period, the adenosine triphosphate
      amount in liver cells was strongly reduced and lipolysis of triglycerides seemed
      to be enhanced. The glycogen stored in liver was first converted into glucose,
      but contrary to what happens in postmortem muscles, glucose was not converted
      into lactate. 

PMID- 24879705
TI  - Hot-boning enhances cook yield of boneless skinless chicken thighs.
AB  - Three experiments were conducted to evaluate the effects of postmortem deboning
      time on cook yield of boneless skinless chicken thighs. In experiment 1, chicken
      thigh meat was deboned at 0.75 (hot-bone), 2, and 24 h postmortem (PM) and
      trimmed to obtain mainly iliotibialis muscle. Samples were cooked directly from a
      frozen state. Cook yield of the muscle was significantly influenced by PM
      deboning time. Hot-boned thighs exhibited a 7% greater cook yield than the
      samples deboned at 24 h. In experiment 2, boneless skinless chicken thighs were
      deboned at 0.3, 2, and 24 h PM and cooked directly from a fresh, never-frozen
      state at 24 h PM. Cook yield of the hot-boned thighs was significantly higher
      than those of the 2 and 24 h deboned samples, which did not differ from each
      other. In experiment 3, whole legs (thigh + drumstick) were cut from the carcass
      backbone at 0.3 (hot-cut), 2, and 24 h PM. Thighs were separated from the legs
      (drumsticks) at either the same time the whole legs were removed from the
      carcasses or at 24 h PM. Intact thighs (bone in) were cooked fresh at 24 h PM.
      Color of fresh thigh muscles, cook yield, and Warner-Bratzler shear force of
      cooked samples were measured. Cook yield of the thighs cut from the backbone
      before chilling was significantly higher than those cut from the carcasses at 2
      and 24 h PM, which did not differ from each other. The PM time at which intact
      thighs were separated from the leg (drumstick) did not influence cook yield.
      These results demonstrate that postmortem deboning time can significantly affect
      cook yield of boneless skinless chicken thigh products. Deboning chicken thighs
      after chilling reduces the cook yield. Differences in the cook yield of thighs
      may also result from the removal of whole chicken legs from the carcass backbone.

PMID- 24879707
TI  - Microbiological quality and biogenic amines in ready-to-eat grilled chicken
      fillets under vacuum packing, freezing, and high-dose irradiation.
AB  - The combined effects of cooking, vacuum packing, freezing, and high-dose gamma
      irradiation in the microbiological conservation and in biogenic amine (BA)
      contents of ready-to-eat grilled breast chicken fillets are investigated in this
      work. After seasoning, cooking, and vacuum packing, one-third of the samples were
      stored at -25 degrees C (T1). The remaining two-thirds were treated with 48 kGy,
      one-third being stored at -25 degrees C (T2) and the other one-third kept at room
      temperature (T3). All samples were periodically analyzed to determine growth of
      heterotrophic aerobic mesophilic bacteria (HAMB) and levels of BA (tyramine, TYM;
      putrescine, PUT; cadaverine, CAD; spermidine, SPD; histamine, HYM; and spermine,
      SPM). Variance analysis was performed to determine significant changes in the
      measured data. Grilling caused HAMB counts in seasoned samples to drop from 5.3
      log cfu/g to zero. In addition, no viable HAMB cells were detected in the samples
      throughout the 12-mo storage time. Regarding the BA analyses, the highest mean
      levels were measured for SPM and CAD with significantly higher levels (P < 0.05)
      being determined in nonirradiated samples (T1). Furthermore, significantly lower
      mean levels for the total content of BA were observed in the irradiated samples.
      Relative to T1 (7.5 +/- 1.5 mg/kg), the figures were 47 +/- 23% for T2 and 60 +/-
      25% for T3, mostly due to loss of CAD by radiolysis. Therefore, it can be
      concluded that the combination of grilling, vacuum packing, freezing, and high
      dose gamma irradiation efficiently eliminated HAMB, while sustaining acceptable
      levels of BA in ready-to-eat chicken breast fillets throughout the 12 mo of
      storage at room temperature. 

PMID- 24879706
TI  - Dietary antioxidant supplementation enhances lipid and protein oxidative
      stability of chicken broiler meat through promotion of antioxidant enzyme
      activity.
AB  - Recent nutrigenomic studies have shown that animal nutrition can have a major
      influence on tissue gene expression. Dietary antioxidant supplements can enhance
      the quality of meat through modification of tissue metabolic processes. This
      study investigated the influence of dietary antioxidants and quality of oil on
      the oxidative and enzymatic properties of chicken broiler breast meat stored in
      an oxygen-enriched package (HiOx: 80% O2/20% CO2) in comparison with air
      permeable polyvinylchloride (PVC) or skin packaging systems during retail display
      at 2 to 4 degrees C for up to 21 d. Broilers were fed either a diet with a low
      oxidized (peroxide value 23 mEq of O2/kg) or high-oxidized (peroxide value 121
      mEq of O2/kg) oil, supplemented with or without an algae-based Se yeast and
      organic mineral antioxidant pack for 42 d. Lipid and protein oxidation and tissue
      enzymatic activity were analyzed. In all packaging systems, lipid oxidation (TBA
      reactive substances) was inhibited by up to 32.5% (P < 0.05) with an antioxidant
      supplemented diet when compared with diets without antioxidants, particularly in
      the HiOx and PVC systems. Protein sulfhydryls were significantly protected by
      antioxidant diets (e.g., by 14.6 and 17.8% for low-and high-oxidized dietary
      groups, respectively, in PVC d 7 samples). Glutathione peroxidase, catalase, and
      superoxide dismutase activities were significantly higher (P < 0.05) in
      antioxidant-supplemented diets compared with the basal diet, regardless of oil
      quality. Also, serum carbonyls were lower in broilers fed a low-oxidized
      antioxidant-supplemented treatment. The results demonstrate that dietary
      antioxidants can minimize the oxidative instability of proteins and lipids, and
      the protection may be linked to improved cellular antioxidant enzymatic activity.

PMID- 24879708
TI  - Antimicrobial resistance among Campylobacter spp. strains isolated from different
      poultry production systems at slaughterhouse level.
AB  - The aim of the current work was to evaluate the prevalence and antimicrobial
      susceptibility of Campylobacter spp. isolated from different chicken production
      systems at the slaughterhouse level. Chicken sampling at slaughterhouse was
      performed for cecum, carcass, and breast meat from flocks of organic (n = 6),
      extensive indoor (n = 14), and intensive production (n = 14), totaling 34 ceca
      pools, 64 neck skin pools, and 132 breasts, representing 96,386 chickens. A
      collection of 167 strains were identified as Campylobacter coli (n = 85) and
      Campylobacter jejuni (n = 82) and were tested for susceptibility to 11
      antimicrobial agents by the disk diffusion method. The frequency of Campylobacter
      in chicken samples from different production systems was between 79 and 100%.
      Campylobacter isolated from all origins were resistant to the fluoroquinolones
      studied (80-98%). However, for ciprofloxacin and ofloxacin, the Campylobacter
      isolates from extensive indoor chicken were significantly (P < 0.05) less
      resistant (77 and 58%) than that from organic (97 and 91%) and intensive
      production (96 and 95%). A high probability of tetracycline resistance occurrence
      was also found for the Campylobacter spp. tested (58% for C. jejuni and 76% for
      C. coli). A more frequent profile of multidrug resistance was noticed for
      isolates from intensive and organic production than for extensive indoor
      production. These results reinforce the need of efficient strategy implementation
      to control and reduce Campylobacter in chickens at production and slaughter
      levels, and the necessity to reduce the use of antimicrobials in poultry sector. 

PMID- 24879709
TI  - Rapid identification of Campylobacter jejuni from poultry carcasses and
      slaughtering environment samples by real-time PCR.
AB  - The objective of this study was to develop a real-time PCR assay for rapid
      identification of Campylobacter jejuni and to apply the method in analyzing
      samples from poultry processing. A C. jejuni-specific primer set targeting a
      portion of the C. jejuni hippuricase gene was developed. The specificity of the
      newly designed primer pair was verified using 5 C. jejuni strains and 20 other
      bacterial strains. Sensitivity was determined to be as low as 1 genome copy per
      reaction. A total of 73 samples were collected at different sites along the
      processing line during 2 visits to a poultry slaughterhouse and were examined by
      direct plating onto modified charcoal cefoperazone deoxycholate agar or after
      enrichment in Bolton broth followed by plating on modified charcoal cefoperazone
      deoxycholate agar. The newly developed real-time PCR assay was used to identify
      the presumptive colonies as belonging to C. jejuni. A real-time PCR assay
      targeting 16S ribosomal RNA was also applied to determine Campylobacter spp.
      prevalence. Results from the real-time PCR analysis indicated considerable
      variability in Campylobacter contamination, with incidence rates of 72.7 and
      27.6% for sampling days A and B, respectively. Campylobacter was isolated from
      100% of prescalded and preeviscerated carcasses on sampling day A. In contrast,
      on sampling day B, the highest number of Campylobacter-positive carcasses was
      recovered after evisceration (60%). The chilling process significantly reduced (P
      < 0.05) Campylobacter population, but the percentage of positive samples on
      sampling day A increased to 80%. All samples collected from the processing
      environment, except scalding tank 3 and the prechiller and chiller tanks, were
      100% positive on day A, whereas no campylobacters were isolated from machinery on
      sampling day B. Our results revealed the widespread of C. jejuni in poultry
      processing and proved that the newly developed real-time PCR assay is a simple,
      specific, and inexpensive method for rapid C. jejuni identification. The newly
      developed PCR method can be easily used in laboratories for reliable and
      unambiguous identification of C. jejuni in poultry samples. 

PMID- 24879710
TI  - Ischemic postconditioning does not improve peripheral endothelial function in ST
      segment elevation myocardial infarction patients.
AB  - The purpose of this study was to determine whether ischemic postconditioning
      (IPC) could improve peripheral endothelial function in patients with acute ST
      segment elevation myocardial infarction (STEMI) undergoing primary percutaneous
      coronary intervention (PCI). Of 102 patients randomly assigned to an IPC or
      standard protocol to study infarct size utilizing cardiovascular magnetic
      resonance imaging, 84 patients had peripheral endothelial function assessed with
      brachial ultrasound measures and peripheral arterial tonometry (PAT) during
      reactive hyperemia 3 days after PCI. Overall IPC was not associated with a
      smaller infarct size compared to controls, though there was a trend towards
      greater myocardial salvage with IPC. Patients randomized to IPC (n=43; age 56 +/-
      11 years; 85% male) and standard protocol (n=41; age 56 +/- 10 years; 88% male)
      underwent endothelial function assessment. Flow mediated vasodilatation was not
      significantly greater in the IPC group than in the standard group (7.4 +/- 4.9%
      versus 6.6 +/- 4.0% respectively, p=0.40) nor was peak hyperemic velocity-time
      integral (78 +/- 26 cm versus 71 +/- 30 cm respectively, p=0.28). Similarly, the
      PAT hyperemic ratio was not significantly greater in the IPC group than in the
      standard group (2.0 +/- 0.9 versus 1.8 +/- 0.6 respectively, p=0.14). In
      conclusion, IPC did not improve early peripheral endothelial function in patients
      with STEMI undergoing primary PCI.

PMID- 24879711
TI  - Endovascular model of abdominal aortic aneurysm induction in swine.
AB  - Abdominal aortic aneurysms are among the main causes of death. The high morbidity
      and mortality associated with aneurysm rupture and repair represents a challenge
      for surgeons and high risk for patients. Although experimental models are useful
      to understand, train, and develop new treatment and diagnostic methods for this
      pathology, animal models developed to date are far from ideal. Animals are either
      too small and do not represent the pathology of humans, or the procedures employ
      laparotomy, or the aortic behavior does not resemble that of a true aneurysm. We
      developed a novel, less invasive and effective method to induce true aortic
      aneurysms in Large White pigs. Animals were submitted to an endovascular chemical
      induction using either calcium chloride (25%) or swine pancreatic elastase.
      Controls were exposed to saline solution. All animals were operated on using the
      same surgical technique under general anesthesia. They were followed weekly with
      ultrasound examinations and at 4 weeks the aorta was harvested. Although elastase
      induced only arterial dilation, imaging, histological, and biomechanical studies
      of the aorta revealed the formation of true aneurysms in animals exposed to
      calcium chloride. Aneurysms in the latter group had biomechanical failure
      properties similar to those of human aneurysms. These findings indicate that the
      endovascular approach is viable and does not cause retroperitoneal fibrosis.

PMID- 24879712
TI  - ICAM-1 and SRD5A1 gene polymorphisms in symptomatic peripheral artery disease.
AB  - The genotype distribution of two gene polymorphisms, previously associated with
      peripheral artery disease (PAD), has been evaluated in a population of diabetic
      (DPAD) and non-diabetic (NDPAD) patients affected by symptomatic PAD (stages II
      IV). A decreased frequency of the AA genotype of rs5498 (ICAM-1) was observed in
      the PAD subjects compared to controls but this result did not reach statistical
      significance (p=0.06 by chi-squared test). On the contrary, a significant
      increase in the frequency of the GG homozygous genotype of rs248793 (SRD5A1) was
      observed in the PAD patient group in comparison to controls (p=0.01). These data
      confirm that the GG genotype of rs248793 in the SRD5A1 gene is significantly
      associated with symptomatic PAD and show a trend towards a stronger association
      with the non-diabetic status.

PMID- 24879713
TI  - Use of fractional flow reserve in the assessment of chronic mesenteric ischemia.
AB  - Chronic mesenteric ischemia (CMI) is a rare condition that is usually the result
      of atherosclerotic obstructive disease affecting the mesenteric arteries. The
      classic triad of post-prandial pain, food aversion and weight loss is not always
      present, often leading to low clinical suspicion for CMI and underdiagnosis. Non
      invasive evaluation for CMI usually starts with mesenteric arterial duplex
      scanning, followed by computed tomography angiography, magnetic resonance
      angiography or conventional angiography, the latter being the gold standard for
      establishing its diagnosis. However, angiography alone has been demonstrated in
      coronary and other vascular beds to be inaccurate in predicting the physiologic
      and hemodynamic significance of a certain subset of atherosclerotic stenoses. We
      present the case of a patient with risk factors and symptoms suggestive of CMI
      who underwent angiography. However, angiography was equivocal and invasive
      physiologic testing was required to confirm the diagnosis and guide
      revascularization.

PMID- 24879714
TI  - Use of fractional flow reserve in the assessment of chronic mesenteric ischemia.

PMID- 24879715
TI  - Controversies regarding the new oral anticoagulants for stroke prevention in
      patients with atrial fibrillation.
AB  - Increasing use of the new oral anticoagulants (NOACs) - dabigatran, rivaroxaban,
      and apixaban - has prompted considerable discussion in the medical community even
      as warfarin remains the mainstay of therapy. This article raises 10 controversial
      issues regarding the use of NOACs for stroke prevention in patients with atrial
      fibrillation, and offers a review of the latest available evidence. We provide a
      brief overview of the mechanism and dosing of these drugs, as well as a summary
      of the key clinical trials that have brought them into the spotlight. Comparative
      considerations relative to warfarin such as NOAC safety, efficacy, bleeding risk,
      reversibility, drug-transitioning and use in patients well controlled on warfarin
      are addressed. Use in select populations such as the elderly, those with coronary
      disease, renal impairment, or on multiple anti-platelet drugs is also discussed.
      Finally, we consider such specific issues as comparative efficacy, off-label use,
      cost, rebound and management during events. Ultimately, the rise of the NOACs to
      mainstream use will depend on further data and clinical experience amongst the
      medical community.

PMID- 24879716
TI  - The role of novel anticoagulants in the management of venous thromboembolism.
AB  - Venous thromboembolism (VTE) is a common health condition with a high mortality
      and morbidity as well as significant health cost. Traditional treatment with
      parenteral heparin followed by vitamin K antagonist (VKA) has helped to decrease
      both morbidity and mortality over years. However, difficulties with warfarin such
      as INR monitoring, drug-drug interactions, and dietary restrictions has led to
      research for new anticoagulants. Thus, novel anticoagulants such as direct
      thrombin and factor X inhibitors have been developed and studied for various
      indications including the management of VTE. There is now good evidence that some
      novel anticoagulants are at least as effective as traditional anticoagulation
      therapy with probably safer outcomes. We have reviewed the literature on the
      medical management of VTE with the focus on the role of dabigatran, rivaroxaban,
      apixaban and edoxaban for this indication.

PMID- 24879717
TI  - Vascular Disease Patient Information Page: Peripheral artery disease.

PMID- 24879718
TI  - Abstracts from the 2014 - 25th Anniversary SVM Scientific Sessions.

PMID- 24879719
TI  - Message from the President.

PMID- 24879721
TI  - A young pregnant woman with spontaneous carotid artery dissection--unknown
      mechanisms.
AB  - Spontaneous carotid artery dissection in pregnancy has not been reported before.
      We present a case of a 31-year-old Caucasian woman who was 11 weeks pregnant and
      presented with neck pain, headache, vomiting and left side Horner's syndrome.
      Subsequent investigations with MR angiography confirmed spontaneous left internal
      carotid artery dissection.

PMID- 24879722
TI  - A twist in the tale: epiploic appendagitis mimicking acute appendicitis.

PMID- 24879720
TI  - Otoscope fogging: examination finding for perforated tympanic membrane.
AB  - The author reports a recently recognised physical examination finding, otoscope
      fogging, for perforated tympanic membrane. Otoscope fogging is defined as
      condensation forming in the view field of the otoscope while inspecting the ear.
      In the setting of occult perforation secondary to the inability to visualise the
      entire tympanic membrane, otoscope fogging may provide the clinician with
      valuable information since medical management may differ if perforation is
      present. 

PMID- 24879723
TI  - Systemic thrombolysis: cure for prosthetic mitral valve thrombosis in the
      comorbid, non-surgical candidate.
AB  - Severe haemolytic anaemia is a rare complication of prosthetic valve thrombosis
      (PVT). Emergent surgical replacement of the affected valve is normally the
      treatment of choice unless contraindicated, such as in high surgical risk
      patients. Systemic thrombolysis is the alternative to surgical valve replacement.
      The purpose of this report is to highlight the unique case of an elderly man with
      New York Heart Association class IV heart failure, history of extensive
      cardiopulmonary surgeries and haemorrhagic stroke, who presented with severe
      haemolytic anaemia secondary to prosthetic mitral valve thrombosis. After
      weighing the risks and benefits, our decision was to use systemic thrombolytic
      therapy, even in light of the patient's previous intracranial haemorrhage.
      Pretreatment and post-treatment Doppler echocardiography showed markedly reduced
      regurgitant jetting that ultimately resolved completely, thereby eliminating the
      underlying cause of haemolysis and achieving symptom resolution. 

PMID- 24879724
TI  - Drug-induced thrombocytopenia secondary to natalizumab treatment.
AB  - A 52-year-old woman with a 10-year history of relapsing-remitting multiple
      sclerosis (RRMS) was started on natalizumab after she developed side effects for
      interferon beta-1a and glatiramer acetate. The patient presented with acute
      severe infusion reaction after the third treatment with natalizumab, developing
      whole-body purpura. Laboratory testing revealed progressive worsening
      thrombocytopenia up to 3 weeks following natalizumab discontinuation. Platelet
      antibodies to platelet-specific antigen as well as antibodies against natalizumab
      were positive. Bone marrow biopsy was negative. The patient was diagnosed with
      drug-induced immune thrombocytopenia (DITP) as a rare case of natalizumab side
      effect which was treated with intravenous methylprednisolone followed by
      rituximab with successful resolution of thrombocytopenia. The patient had a
      stable course of RRMS with no relapses and no brain MRI changes at 2 years after
      initiation of rituximab.

PMID- 24879725
TI  - Ureteric access sheath aided insertion of resonance metal ureteric stent.
AB  - Ureteral obstruction caused by malignancy is a challenging and often complicated
      problem for urologists. We present a novel technique of ureteric access sheath
      aided insertion of a Resonance metal ureteric stent in the setting of a difficult
      obstruction. 

PMID- 24879726
TI  - Incidental finding of papillary thyroid carcinoma with BRAFV600E mutation in a
      patient with coexistent primary hyperparathyroidism and Graves' hyperthyroidism.
AB  - The simultaneous occurrence of hyperthyroidism and hyperparathyroidism was
      previously reported to be rare, but it was recognised more and more clearly by
      effective evaluations. Recent studies also mentioned the coexistence of
      parathyroid adenoma and papillary thyroid carcinoma (PTC). The potential
      mechanism is still unknown. We report a case of a 46-year-old man coexisted with
      primary hyperparathyroidism, Graves' hyperthyroidism and occult PTC. The patient
      had a 6-month history of polyphagia and irritability. Blood examinations showed
      elevated serum calcium and parathyroid hormone levels. Serum phosphate was lower.
      Thyroid function evaluation indicted Graves' hyperthyroidism. Ultrasound showed a
      solitary hyperchoic thyroid nodule in the right gland. Parathyroid radioisotope
      scanning found a mild enhancement of 99mTc absorption in the lower part of the
      right parathyroid gland. A surgical exploration was carried out and the
      parathyroid adenoma resection was performed. An occult micro-PTC with BRAF(V600E)
      mutation was also detected. 

PMID- 24879727
TI  - Recruitment of renal transplant patients into patrolling police roles using
      orthotic shields.
AB  - Renal allografts are transplanted to an anatomically unnatural site where they
      are exposed to trauma, and may fail if damaged. Individuals with renal allografts
      have been excluded from patrolling police roles as these often necessitate
      confrontation. We describe two patients with renal allografts who have been
      recruited by the Metropolitan Police Service, using bespoke orthotic shields to
      protect the grafts. 

PMID- 24879728
TI  - Sleeping with the fishes: electromagnetic interference causing an inappropriate
      implantable cardioverter defibrillator shock.
AB  - A 60-year-old man with a cardiac defibrillator implanted due to previous
      ventricular fibrillation arrest and ischaemic cardiomyopathy received a shock
      while cleaning his fish pond. At the time, his immersed arm was close to a
      submersed water pump, but the patient was asymptomatic. As a result of the shock
      he lost consciousness, but collapsed backwards, away from the pond. Interrogation
      of the device revealed a high-frequency artefact that was sensed by the device
      and triggered a shock. Device parameters were otherwise normal. Subsequently, the
      submersed water pump was found to be the source of an external alternating
      current leak and was identified as the likely cause of the inappropriate shock
      due to electromagnetic interference (EMI). Awareness of potential sources of EMI
      along with evaluation of data with a detailed clinical history is warranted in
      all cases. 

PMID- 24879730
TI  - Pleuropericardial effusion: an unusual presentation of polymyalgia rheumatica.
AB  - Polymyalgia rheumatica (PMR) is an idiopathic systemic inflammatory condition
      manifesting as aches and muscle stiffness of the proximal muscle groups. Very
      rarely, PMR can be associated with serositis. We report a very rare case of PMR
      where the patient's primary presentation was a pleuropericardial syndrome
      (pleuropericardial effusion). 

PMID- 24879729
TI  - A surprising cause of reversible dilated cardiomyopathy.
AB  - This case report describes two cases of dilated cardiomyopathy due to
      hypocalcaemia as a result of hypoparathyroidism. Patient A suffered from dilated
      cardiomyopathy due to secondary hypoparathyroidism as a result of previous neck
      surgery. Patient B suffered from dilated cardiomyopathy with congestive heart
      failure due to primary hypoparathyroidism. Hypoparathyroidism can exist for years
      before being recognised, especially after neck surgery. Besides standard
      treatment of heart failure, restoration of serum calcium levels with calcium and
      vitamin D supplementation can lead to rapid improvement of cardiac function and
      should be continued lifelong. Both patients were responding very well to heart
      failure therapy and calcium supplementation as ejection fraction improved after
      restoration of plasma calcium levels. This case report emphasises that
      hypocalcaemia should be in the differential diagnosis of heart failure. 

PMID- 24879731
TI  - Acute necrotising pancreatitis: a late and fatal complication of
      pancreaticoduodenal arterial embolisation.
AB  - A 70-year-old man was diagnosed with a massive bleeding duodenal ulcer which was
      refractory to emergency endoscopic management. Angiogram of the coeliac and
      superior mesenteric arteries revealed bleeding from the superior and inferior
      pancreaticoduodenal arteries. Transcatheter arterial embolisation of superior and
      inferior pancreaticoduodenal arteries along with the gastroduodenal artery was
      performed. Two weeks later he developed severe necrotising pancreatitis of the
      pancreatic head probably due to ischaemia, which was managed conservatively.
      Three months later the patient experienced another episode of pancreatitis which
      progressed into multiorgan dysfunction and the patient passed away. 

PMID- 24879732
TI  - Urolithiasis in primary obstructive megaureter: a management dilemma.
AB  - Megaureter with urolithiasis is an uncommon entity. These stones may be located
      in the kidney, ureter or both. Management of these cases is difficult due to free
      mobility and stone multiplicity. As there are no guidelines about the management,
      the surgeon usually manages according to her/his experience, stone location or
      burden. The goal is to remove the stones and reimplant the ureters in the same
      session, if possible. We describe single-stage management of one such patient who
      presented with bilateral multiple ureteral and left renal stones. The left
      ureteral stones were first flushed into the kidney by the ureteroscope.
      Percutaneous nephrolithotomy was then performed and stones were removed intact.
      The patient was then turned supine and the location of right ureteral stones was
      confirmed by fluoroscopy in the same location (right lower ureter). The patient
      underwent successful bilateral ureteroneocystostomy with simultaneous removal of
      right lower ureteral stones. 

PMID- 24879733
TI  - Treatment of myelitis in Behcet's disease with rituximab.
AB  - Behcet's disease (BD) is a chronic inflammatory disorder that involves the
      parenchymal central nervous system (neuro-BD, NBD) approximately in 5-49% of
      patients, causing lesions rarely located in the spinal cord (SC). We report the
      first case of NBD-myelitis treated with intravenous rituximab. A 41-year-old man
      affected by BD presented with mild paraparesis with a miliary involvement and a
      'net-like' gadolinium enhancement (Gde) of the SC. After a therapeutic attempt
      with pulsed cyclophosphamide and intravenous methylprednisolone, the clinical and
      neuroradiological course worsened. A progressive improvement was observed after
      rituximab administration associated with low doses of oral prednisone. No disease
      activity was detected and the patient reported no adverse event. After six
      rituximab cycles, cervical MRI was normal while thoracic MRI showed a slight T2
      weighted hyperintensity of D4-D10 spinal tract without Gde. A combined use of
      rituximab and oral steroids resulted in a long-term suppression of NBD activity
      without any safety concern. 

PMID- 24879734
TI  - Unusual presentation of a scrotal tumour.
AB  - A 59-year-old man had a wide excision of the right-sided scrotal cancer in the
      neck of the scrotum. On dissection it became apparent that the tumour had
      developed a blood supply from the right spermatic cord. Histology revealed G2T2
      squamous cell carcinoma. A biopsy from an abnormal skin area from the opposite
      groin reported chronic folliculitis. He underwent an ultrasound scanning of the
      groin and fine-needle aspiration, which did not show any suspicious features.
      Follow-up CT of the abdomen and pelvis after 6 weeks did not show any evidence of
      intra-abdominal lymphadenopathy. Another CT has been arranged within the next 3
      months to confirm that the spread of the tumour does not follow the pattern of a
      testicular tumour.

PMID- 24879735
TI  - Migration of a strand of four seeds in low-dose-rate brachytherapy.
AB  - We report a case of stranded-seed migration (one strand of four seeds), via the
      prostatic venous plexus to the internal pudendal vein, in low-dose-rate (LDR)
      prostate brachytherapy. A 70-year-old man with low-risk prostate adenocarcinoma
      underwent transperineal permanent seed implantation. A total of 93 iodine-125
      seeds were implanted (91 stranded seeds and 2 loose seeds). Immediate
      postimplantation fluoroscopic image and day 1 postimplantation CT scan indicated
      all implanted seeds to be within the vicinity of the prostate as planned. Day 30
      pelvic X-ray and CT scan revealed migration of a strand of four seeds to the
      right pelvis (adjacent to ischial spine). At 2 years postimplantation, the
      patient continues to have good disease control with prostate specific antigen
      level of 0.69 MUg/L, and asymptomatic. To the best of our knowledge, this is the
      first report of migration of an entire strand of seeds following LDR prostate
      brachytherapy.

PMID- 24879736
TI  - Biventricular thrombosis in a structurally normal heart at high altitude.
AB  - We present a rare case of biventricular thrombus in a young patient with a
      structurally normal heart at high altitude, complicated with pulmonary embolism.
      Detailed evaluation revealed him to have protein S deficiency. Altered
      environmental conditions at high altitude associated with protein S deficiency
      resulted in thrombus formation at an unusual location; the same is discussed in
      this case report. 

PMID- 24879737
TI  - Survival after an amniotic fluid embolism following the use of sodium
      bicarbonate.
AB  - Amniotic fluid embolism (AFE) is a rare and potentially fatal complication of
      pregnancy. In this case report, we highlight the successful use of sodium
      bicarbonate in a patient with an AFE. We present a case of a 38-year-old mother
      admitted for an elective caesarean section. Following the delivery of her baby,
      the mother suffered a cardiac arrest. Following a protracted resuscitation,
      transoesophageal echocardiography demonstrated evidence of acute pulmonary
      hypertension, with an empty left ventricle and an over-distended right ventricle.
      In view of these findings and no improvement noted from on-going resuscitation,
      sodium bicarbonate was infused as a pulmonary vasodilator. Almost instantaneous
      return of spontaneous circulation was noted, with normalisation of cardiac
      parameters. We propose that in patients suspected with AFE and who have been
      unresponsive to advance cardiac life support measures, and where right
      ventricular failure is present with acidosis and/or hypercarbia, the use of
      sodium bicarbonate should be considered. 

PMID- 24879738
TI  - Extreme coronary artery tortuosity in association with tortuosity of the systemic
      arteries: a rare and challenging situation for the interventionist.

PMID- 24879739
TI  - A non-fatal intoxication with a high-dose sodium nitrate.
AB  - A 67-year-old man accidentally ingested 75 g of sodium nitrate. He had instant
      gastrointestinal symptoms. On physical examination, he was respiratorily and
      haemodynamically stable and there were no signs of central or peripheral
      cyanosis. Repeated methaemoglobin levels were normal and he made an uneventful
      recovery. Sodium nitrate intoxication is rare. Serious effects can occur, mainly
      through formation of nitrite and nitric oxide, which can cause
      methaemoglobinaemia and vasodilation. Even if the presenting symptoms are mild,
      it is important to remain cautious since more serious symptoms can occur later.
      Monitoring of respiratory and haemodynamic status and repeated blood gas analysis
      in order to detect methaemoglobinaemia are recommended. 

PMID- 24879740
TI  - LBBB masking the ECG changes of inferior wall infarction: a caution to be
      vigilant.

PMID- 24879741
TI  - Male sexual function and pelvic floor surgery of their female partner: A one-year
      follow-up study.
AB  - OBJECTIVE: The aim of this study was to examine if sexual function of male
      partners changed after surgery for pelvic floor disorders and to explore
      associated factors. STUDY DESIGN: This was an observational follow-up study at
      the Gynecological Department at the St Olavs University Hospital, Trondheim. The
      sample consisted of 35 male partners of women scheduled for pelvic organ prolapse
      or stress urinary incontinence surgery. Self-administered questionnaires,
      containing validated instruments as well as exploratory questions, were sent to
      women and their partners before and one year after pelvic floor surgery. Vaginal
      dimensions were measured in all women according to the Pelvic Organ Prolapse
      Quantification System, both before and after the surgery. MAIN OUTCOME MEASURES:
      The Brief Sexual Function Instrument and the presence of erectile dysfunction.
      RESULTS: One year after pelvic floor surgery, scores for sexual drive, erection
      and overall satisfaction from the Brief Sexual Function Instrument were
      unchanged; the ejaculation score (range 0-4) had mildly improved from a range of
      4 (median 4) to a range of 3.5 (median 4), (p = 0.014). The proportion of men
      with erectile dysfunction was unchanged, while the proportion of men reporting
      vaginal wind had significantly decreased (p = 0.016). None of the baseline
      factors, subjective experiences or vaginal dimensions at baseline or follow-up
      were associated with the improved ejaculation score; only a reduction in the
      proportion of men reporting their partners with dyspareunia (ns) was
      significantly correlated (Spearman's rho 0.42, p = 0.019). CONCLUSION: Sexual
      function of male partners was unchanged or mildly improved after pelvic floor
      surgery.

PMID- 24879742
TI  - Faecal incontinence: a life-course approach.
AB  - Faecal incontinence is under-reported and under-diagnosed. It is associated with
      negative social and psychological sequelae and reduced quality of life. Timely
      intervention potentially reduces its adverse impact throughout the life-course as
      most cases are potentially treatable. This review provides a summary of pre
      disposing factors. It offers an overview of preventative and treatment options
      within the community setting, with signposting to further reading and a call to
      further research into this area of women's health. 

PMID- 24879743
TI  - Urogenital atrophy.
AB  - The British Menopause Society Council aims to aid health professionals in
      providing up to date and informed advice about post reproductive health. This
      guidance refers to the long-term, but often ignored condition of urogenital
      atrophy resulting from postmenopausal estrogen deficiency. Treatment should be
      based on up to date information and targeted to the needs of the individual
      woman. Non-estrogen- and estrogen-containing treatments are discussed.

PMID- 24879744
TI  - Premature menopause - Meeting the needs.
AB  - Premature menopause is characterized by amenorrhea, elevated gonadotropin levels
      and sex steroid deficiency occurring in women below 40 years of age.
      Heterogeneity of premature ovarian failure is reflected by various causes, both
      spontaneous and iatrogenic. X chromosomal abnormalities remain the main cause of
      primary ovarian insufficiency. Women with primary ovarian insufficiency present
      with amenorrhea, irregular cycles, signs of estrogen deficiency and infertility.
      They are at increased risk for non-communicable diseases such as, cardiovascular
      disease, Alzheimer's disease, and osteoporosis. Management includes use of
      menopausal hormone therapy till the age of natural menopause and customized as
      per the needs. In women having fertility issues, IVF with donor oocytes remains
      the treatment of choice with the best results. With advances in assisted
      reproductive technologies, cryopreservation of oocytes/embryos should be
      utilized, whenever impending primary ovarian insufficiency is anticipated either
      due to therapy or biological reasons.

PMID- 24879745
TI  - Implications of off-label use: An example from the final results of an
      observational cohort study on Intrinsa(r) (testosterone patch).
AB  - INTRODUCTION: Off-label use is where a medicinal product is used for a medical
      purpose not in accordance with the authorised product information. Intrinsa(r) is
      a transdermal testosterone patch, which is indicated for use in hypoactive sexual
      desire disorder in bilaterally oophorectomised and hysterectomised women
      receiving concomitant estrogen therapy. OBJECTIVES: To describe the utilization
      characteristics of patients prescribed testosterone patch (Intrinsa(r)) and to
      assess, where possible, if the product is being used according to the authorised
      product information. STUDY DESIGN: Patients identified from dispensed
      prescriptions issued by general practitioners for Intrinsa(r) between March 2007
      and August 2010. Postal questionnaires were sent to general practitioners six
      months following the date of the first prescription for Intrinsa(r) for each
      patient, requesting information including patient demographics and drug
      utilization. MAIN OUTCOME MEASURES: Menopausal status and use of concomitant
      estrogen therapy. RESULTS: The final cohort consisted of 3073 patients; the
      majority were females (3017, 98.2%). The most commonly reported indication was
      hypoactive sexual desire disorder in 2324 female patients (77.0%). Only 43.5%
      female patients (n = 1313) were reported to have been hysterectomised and
      bilaterally oophorectomised. For 1029 (34.1%) female patients there was no
      evidence that the patient was using concomitant estrogen therapy. Overall, only
      643 patients (20.9%) in the cohort were being prescribed Intrinsa(r) according to
      the manufacturer's recommendations. CONCLUSIONS: Evidence obtained solely from
      clinical trials might not be generalisable where off-label prescribing occurs in
      real-life, so evidence from post-marketing observational studies is important to
      provide complimentary data on a product's safety and effectiveness.

PMID- 24879746
TI  - Consensus statement for non-estrogen-based treatments for menopausal symptoms.
AB  - Non-estrogen-based therapies can be used for the treatment of hot flushes, for
      symptoms of urogenital atrophy and for lack of sexual desire and/or fatigue not
      improved by estrogen treatments. Treatment choice should be based on up-to-date
      information and targeted to individual women's needs. Non-hormonal therapies are
      useful particularly for women with estrogen-dependent disease such as breast and
      endometrial cancers.

PMID- 24879747
TI  - Reinventing the general practitioner menopause clinic--personal experiences.
AB  - Menopause is accompanied by a plethora of symptoms. The 10 minute general
      practitioner consultation is ineffective in addressing all these symptoms. My
      experience of offering a 1 hour assessment and management has very positive and
      encouraging results. Should this be made available in general practice and will
      it prove more cost effective in the long run and also lead to greater patient
      satisfaction? 

PMID- 24879748
TI  - Body identical hormone replacement.
AB  - The adverse outcomes seen in the Women's Health Initiative (WHI) 1 were mainly
      due to an over-dosage of hormones in a relatively elderly population. However,
      fundamental differences exist between conjugated equine estrogens and 17 beta
      estradiol and between medroxyprogesterone acetate and natural progesterone. It is
      likely that these differences also contributed to the adverse outcomes in WHI,
      which were contrary to the cardiovascular benefits seen in previous observational
      trials. Recent studies of cardiovascular risk markers in younger women have been
      designed using predominantly estradiol and natural progesterone (transdermal and
      oral) as the primary interventions. This paper reviews the effects that body
      identical estradiol and progesterone can have, both in the physiological
      environment and also when replaced as transdermal estradiol and micronised oral
      progesterone.

PMID- 24879750
TI  - Endoscopic (video) demonstration of hookworm infestation of the stomach.
AB  - Hookworm infestation is common in southern India. The adult worms normally reside
      in the duodenum, graze the intestinal mucosa with their large buccal cavities and
      ingest the intestinal epithelial cells and blood. Depending on the number of
      worms the infection may be either asymptomatic or can cause iron deficiency
      anaemia due to chronic blood loss. Adult worms live in the small intestine and
      are not usually seen in the stomach. There are only very few case reports in the
      literature reporting hookworm infestation of the stomach. In this case report we
      present an endoscopic (video) demonstration of hookworm infestation of the
      stomach in a woman who presented with chronic anaemia. 

PMID- 24879749
TI  - Physical activity and depressive symptoms in four ethnic groups of midlife women.
AB  - The purpose of this study was to determine the associations between physical
      activity and depression and the multiple contextual factors influencing these
      associations in four major ethnic groups of midlife women in the United States.
      This was a secondary analysis of the data from 542 midlife women. The instruments
      included questions on background characteristics and health and menopausal
      status; the Depression Index for Midlife Women (DIMW); and the Kaiser Physical
      Activity Survey (KPAS). The data were analyzed using chi-square tests, the ANOVA,
      two-way ANOVA, correlation analyses, and hierarchical multiple regression
      analyses. The women's depressive symptoms were negatively correlated with active
      living and sports/exercise physical activities whereas they were positively
      correlated with occupational physical activities (p < .01). Family income was the
      strongest predictor of their depressive symptoms. Increasing physical activity
      may improve midlife women's depressive symptoms, but the types of physical
      activity and multiple contextual factors need to be considered in intervention
      development. 

PMID- 24879751
TI  - RFID technology for hazardous waste management and tracking.
AB  - The illegal dumping of hazardous waste is one of the most concerning occurrences
      related to illegal waste activities. The waste management process is quite
      vulnerable, especially when it comes to assuring the right destination for the
      delivery of the hazardous waste. The purpose of this paper is to present a new
      system design and prototype for applying the RFID technology so as to guarantee
      the correct destination for the hazardous waste delivery. The aim of this
      innovative approach, compared with other studies that employ the same technology
      to the waste disposal process, is to focus on the certification that the
      hazardous waste will be delivered to the right destination site and that no
      inappropriate disposal will occur in the transportation stage. These studies were
      carried out based on data collected during visits to two hazardous waste producer
      companies in Brazil, where the material transportation and delivery to a company
      in charge of the waste disposal were closely monitored. 

PMID- 24879753
TI  - No lasting effects of plain packaging on cigarette pack retrieval time in small
      Australian retail outlets.

PMID- 24879752
TI  - Role of Central Serotonin in Anticipation of Rewarding and Punishing Outcomes:
      Effects of Selective Amygdala or Orbitofrontal 5-HT Depletion.
AB  - Understanding the role of serotonin (or 5-hydroxytryptamine, 5-HT) in aversive
      processing has been hampered by the contradictory findings, across studies, of
      increased sensitivity to punishment in terms of subsequent response choice but
      decreased sensitivity to punishment-induced response suppression following gross
      depletion of central 5-HT. To address this apparent discrepancy, the present
      study determined whether both effects could be found in the same animals by
      performing localized 5-HT depletions in the amygdala or orbitofrontal cortex
      (OFC) of a New World monkey, the common marmoset. 5-HT depletion in the amygdala
      impaired response choice on a probabilistic visual discrimination task by
      increasing the effectiveness of misleading, or false, punishment and reward, and
      decreased response suppression in a variable interval test of punishment
      sensitivity that employed the same reward and punisher. 5-HT depletion in the OFC
      also disrupted probabilistic discrimination learning and decreased response
      suppression. Computational modeling of behavior on the discrimination task showed
      that the lesions reduced reinforcement sensitivity. A novel, unitary account of
      the findings in terms of the causal role of 5-HT in the anticipation of both
      negative and positive motivational outcomes is proposed and discussed in relation
      to current theories of 5-HT function and our understanding of mood and anxiety
      disorders. 

PMID- 24879754
TI  - Increasing dietary neutral detergent fiber concentration decreases ruminal
      hydrogen sulfide concentrations in steers fed high-sulfur diets based on ethanol
      coproducts.
AB  - Cattle feedlot diets commonly contain ethanol coproducts that are high in S. This
      dietary S is reduced in the rumen by sulfate reducing bacteria, resulting in an
      accumulation of hydrogen sulfide (H2S), increasing the risk for S toxicity. A
      negative correlation between H2S and ruminal pH has been observed previously. The
      objective of this study was to determine the effect of varying dietary NDF from
      chopped bromegrass hay (66% NDF) on performance, ruminal pH, and ruminal H2S gas
      concentration of steers fed a high-S finishing diet. One hundred fifty crossbred
      steers (359 +/- 51 kg BW) were blocked by BW into pens of 5 steers and randomly
      assigned within block to 1 of 5 treatments (n = 6 pens per treatment) and fed for
      84 d. Dietary treatments included 3.5, 5.7, 7.9, 10.1, or 11.4% roughage NDF
      (rNDF) from bromegrass hay and contained 0.46% dietary S from a combination of
      dried distillers grains with solubles and condensed corn distillers solubles. In
      all diets, hay was added at the expense of dry-rolled corn. Effective NDF
      increased linearly (P < 0.01) with increased inclusion of rNDF. Final BW was not
      affected by rNDF (P >= 0.12). The addition of roughage did not affect ADG (P >=
      0.13) or gain efficiency (P >= 0.12). Dry matter intake increased linearly (P <
      0.01) as rNDF concentration increased. There was a treatment * month interaction
      for S intake (P < 0.01), explained by steers fed 3.5 or 11.4% rNDF increasing S
      intake each month whereas the middle rNDF inclusions had similar S intake between
      months 1 and 2 and increased in month 3. Ruminal H2S concentrations and ruminal
      fluid pH were measured at 6 h postfeeding on d 7, 14, 21, 29, and 84. Ruminal pH
      increased linearly (P < 0.01; 5.48, 5.61, 5.71, 5.74, and 5.80 +/- 0.041 for 3.5,
      5.7, 7.9, 10.1, and 11.4% rNDF, respectively) and ruminal H2S concentrations
      decreased linearly (P < 0.01; 1.00, 0.86, 0.76, 0.70, and 0.62 +/- 0.037 g/m(3)
      for 3.5, 5.7, 7.9, 10.1, and 11.4% rNDF, respectively) as rNDF inclusion
      increased. Using mixed model regression analysis, ruminal pH had a strong
      negative relationship with ruminal H2S concentrations (beta = -0.63; P < 0.01).
      Under conditions of this study, increasing roughage did not affect cattle gains
      but helped maintain greater ruminal pH and decreased H2S concentration,
      suggesting that this dietary strategy may lessen the risk of S toxicity in
      feedlot cattle. 

PMID- 24879755
TI  - Influence of thermally oxidized vegetable oils and animal fats on growth
      performance, liver gene expression, and liver and serum cholesterol and
      triglycerides in young pigs.
AB  - To evaluate the effect of feeding thermally oxidized vegetable oils and animal
      fats on growth performance, liver gene expression, and liver and serum fatty acid
      and cholesterol concentration in young pigs, 102 barrows (6.67 +/- 0.03 kg BW)
      were divided into 3 groups and randomly assigned to dietary treatments in a 4 * 3
      factorial arrangement. The main factors were lipid source (n = 4; corn oil [CN],
      canola oil [CA], poultry fat [PF], and tallow [TL]) and lipid peroxidation level
      (n = 3; original lipids [OL], slow oxidation [SO] through heating at 95 degrees C
      for 72 h, or rapid oxidation [RO] through heating at 185 degrees C for 7 h). Pigs
      were provided ad libitum access to diets in group pens for 28 d followed by
      controlled feed intake in metabolism crates for 10 d. On d 39, all pigs were
      euthanized for liver samples to determine liver weight, lipid profile, and gene
      expression patterns. Lipid oxidation analysis indicated that compared with the
      OL, SO and RO of lipids had a markedly increased concentrations of primary and
      secondary peroxidation products, and the increased lipid peroxidation products in
      CN and CA were greater than those in PF and TL. After a 28-d ad libitum feeding
      period, pigs fed RO lipids tended to have reduced ADFI (P = 0.09) and ADG (P <
      0.05) compared with pigs fed OL, and pigs fed CA had reduced G:F (P < 0.05)
      compared with pigs fed all other lipids. Pigs fed RO lipids tended to have
      increased relative liver weight (P = 0.09) compared with pigs fed OL. Liver
      triglyceride concentration (LTG) in pigs fed OL was greater (P < 0.05) than in
      pigs fed SO lipids and tended to be greater (P < 0.07) than in pigs fed SO. The
      reduced LTG were consistent with increased (P < 0.05) mRNA expression of
      PPARalpha factor target genes (acyl-CoA oxidase, carnitine palmitoyltransferase
      1, and mitochondrial 3-hydroxy-3-methylglutary-CoA synthase) in pigs fed SO and
      RO lipids compared with pigs fed OL. Pigs fed CN or CA tended to have increased
      LTG (P = 0.09) compared with pigs fed TL. Liver cholesterol concentration in pigs
      fed CN was less (P < 0.05) than in pigs fed PF and tended to be less (P = 0.06)
      than in pigs fed TL, whereas pigs fed CA had a reduced (P < 0.05) liver
      cholesterol compared with pigs fed PF or TL. In conclusion, feeding thermally
      oxidized lipids negatively affected growth performance and LTG of young pigs,
      which was associated with an upregulation of fatty acid catabolism pathways. 

PMID- 24879756
TI  - Genetic correlations between body weight change and reproduction traits in Merino
      ewes depend on age.
AB  - Merino sheep in Australia experience periods of variable feed supply. Merino
      sheep can be bred to be more resilient to this variation by losing less BW when
      grazing poor quality pasture and gaining more BW when grazing good quality
      pasture. Therefore, selection on BW change might be economically attractive but
      correlations with other traits in the breeding objective need to be known. The
      genetic correlations (rg) between BW, BW change, and reproduction were estimated
      using records from approximately 7,350 fully pedigreed Merino ewes managed at
      Katanning in Western Australia. Number of lambs and total weight of lambs born
      and weaned were measured on approximately 5,300 2-yr-old ewes, approximately
      4,900 3-yr-old ewes, and approximately 3,600 4-yr-old ewes. On a proportion of
      these ewes BW change was measured: approximately 1,950 2-yr-old ewes,
      approximately 1,500 3-yr-old ewes, and approximately 1,100 4-yr-old ewes. The BW
      measurements were for 3 periods. The first period was during mating period over
      42 d on poor pasture. The second period was during pregnancy over 90 d for ewes
      that got pregnant on poor and medium quality pasture. The third period was during
      lactation over 130 d for ewes that weaned a lamb on good quality pasture. Genetic
      correlations between weight change and reproduction were estimated within age
      classes. Genetic correlations were tested to be significantly greater magnitude
      than 0 using likelihood ratio tests. Nearly all BW had significant positive
      genetic correlations with all reproduction traits. In 2-yr-old ewes, BW change
      during the mating period had a positive genetic correlation with number of lambs
      weaned (rg = 0.58); BW change during pregnancy had a positive genetic correlation
      with total weight of lambs born (rg = 0.33) and a negative genetic correlation
      with number of lambs weaned (rg = -0.49). All other genetic correlations were not
      significantly greater magnitude than 0 but estimates of genetic correlations for
      3-yr-old ewes were generally consistent with these findings. The direction of the
      genetic correlations mostly coincided with the energy requirements of the ewes
      and the stage of maturity of the ewes. In conclusion, optimized selection
      strategies on BW changes to increase resilience will depend on the genetic
      correlations with reproduction and are dependent on age. 

PMID- 24879757
TI  - Comparative effects of supplementing beef steers with zilpaterol hydrochloride,
      ractopamine hydrochloride, or no beta agonist on strip loin composition, raw and
      cooked color properties, shear force, and consumer assessment of steaks aged for
      fourteen or twenty-one days postmortem.
AB  - Beef steers (n = 1,914) were assigned to 1 of 3 beta-adrenergic agonist (betaAA)
      supplementation treatments-zilpaterol hydrochloride (ZH; 8.3 mg/kg of DM for 20 d
      with 3-d withdrawal), ractopamine hydrochloride (RH; 308 mg.head(-1).d(-1) for 28
      d), or no betaAA (CON)-to determine the effects on consumer eating quality. Strip
      loins (n = 1,101; CON = 400, RH = 355, and ZH = 346) were obtained and fabricated
      into 2.5-cm-thick steaks for proximate, Warner-Bratzler shear force (WBSF), slice
      shear force (SSF), and consumer analyses; steaks were aged until 14 or 21 d
      postmortem. Fat and moisture contents were not affected by betaAA supplementation
      (P > 0.05), but strip steaks from steers fed ZH had more protein (P < 0.01) than
      those from steers fed CON or RH, which were similar. An interaction between
      betaAA and aging was observed (P < 0.01) for WBSF but not SSF. Within steaks aged
      14 d, ZH steaks required the most force to shear, RH steaks were intermediate,
      and CON steaks had the lowest WBSF values; however, RH steaks had a stronger
      response to aging than CON or ZH steaks, resulting in the lowest WBSF values at
      21 d. Slice shear force values were greater (P < 0.01) in steaks from steers fed
      ZH than in steaks from steers fed CON or RH, which did not differ. Following
      shear force analyses, steaks within 2 SD of each treatment mean for WBSF were
      selected randomly for consumer assessment of eating quality. Consumer testing (n
      = 400; 200/postmortem aging period) was arranged in a 3 * 3 factorial
      representing 3 quality grades (Select, Low Choice, and Premium Choice) and 3
      treatments (ZH, RH, and CON). In steaks aged 14 d, betaAA supplementation
      affected (P < 0.01) tenderness, flavor, and overall liking and tenderness
      acceptability, resulting in lower consumer scores for ZH than CON and RH;
      however, juiciness, flavor, and overall acceptability were similar (P > 0.05). In
      steaks aged 21 d, feeding betaAA influenced (P < 0.01) only tenderness and
      juiciness scores. Despite these differences, betaAA did not affect (P > 0.05)
      acceptability. Quality grade impacted (P < 0.01) all traits and acceptability in
      steaks aged 14 and 21 d. In 14-d steaks, Premium Choice typically was scored
      higher than Low Choice or Select; however, consumers rated 21-d Low Choice and
      Premium Choice similarly-both receiving greater scores than Select. Consumers
      detected several differences in eating quality at 14 d because of betaAA
      supplementation. Increasing aging from 14 to 21 d mitigated differences in shear
      force and tenderness scores because of feeding ZH, so that tenderness and overall
      acceptability were similar between ZH, RH, and CON. 

PMID- 24879758
TI  - Influence of thermally oxidized vegetable oils and animal fats on energy and
      nutrient digestibility in young pigs.
AB  - A total of 108 barrows (6.67 +/- 0.03 kg BW) were assigned to 12 dietary
      treatments in a 4 * 3 factorial design plus a corn-soybean meal control diet to
      evaluate the effect of lipid source and peroxidation level on DE, ME, and
      apparent total tract digestibility (ATTD) of DM, GE, ether extract (EE), N, and C
      in young pigs. Main effects were lipid source (corn oil [CN], canola oil [CA],
      poultry fat [PF], and tallow [TL]) and peroxidation level (original lipids [OL],
      slow oxidation [SO] of lipids heated for 72 h at 95 degrees C, or rapid oxidation
      [RO] of lipids heated for 7 h at 185 degrees C). Pigs were provided ad libitum
      access to diets for 28 d followed by an 8-d period of controlled feed intake
      equivalent to 4% BW daily. Diets were formulated based on the ME content of CA
      with the standardized ileal digestible Lys, Met, Thr, Trp, total Ca, and
      available P:ME balanced relative to NRC (1998) recommendations. Lipid
      peroxidation analysis indicated that compared with the OL, SO and RO had a
      markedly increased concentrations of lipid peroxidation products, and the
      increase of peroxidation products in CN and CA were greater than those in PF and
      TL. Addition of lipids to diets increased (P < 0.05) ATTD of EE and tended to
      improve (P = 0.06) ATTD of GE compared with pigs fed the control diet. Feeding CN
      or CA increased (P < 0.05) ATTD of DM, GE, EE, N, and C compared with feeding TL,
      while feeding PF improved (P < 0.05) ATTD of GE and EE and tended to increase (P
      = 0.06) ATTD of C compared with TL. Pigs fed CN had increased (P = 0.05)
      percentage N retention than pigs fed TL. No peroxidation level effect or
      interaction between lipid source and peroxidation level on DE and ME was
      observed. Lipid source tended (P = 0.08) to affect DE but not ME values of
      experimental lipids (P > 0.12). Digestible energy values for CA (8,846, 8,682,
      and 8,668 kcal/kg) and CN (8,867, 8,648, and 8,725 kcal/kg) were about 450
      kcal/kg greater than that of TL (8,316, 8,168, and 8,296 kcal/kg), with PF being
      intermediate (8,519, 8,274, and 8,511 kcal/kg), for OL, SO, and RO lipids,
      respectively, respectively. In conclusion, lipid source affected ATTD of dietary
      DM, GE, EE, N, and C, and N retention and tended to influence the DE value of the
      lipid but did not significantly affect their ME value. Rapid and slow heating of
      lipids used in this study increased lipid peroxidation products but had no
      detectable effects on nutrient and energy digestibility as well as DE and ME
      values of the various lipids. 

PMID- 24879759
TI  - Prediction of manure nitrogen and organic matter excretion for young Holstein
      cattle fed on grass silage-based diets.
AB  - The objectives of the present study were to evaluate the effects of sex (steers
      vs. heifers) of young Holstein cattle on N and OM excretion in feces and urine
      and to use these data to develop prediction models for N and OM excretion. Data
      used were derived from a study with 20 autumn-born Holstein cattle (10 steers and
      10 heifers) with N and OM intake and output measured at age of 6, 12, 18, and 22
      mo, respectively. The cattle were offered a typical diet used on U.K. commercial
      farms containing a single grass silage mixed with concentrates. In each period,
      the cattle were housed as a single group in cubicle accommodation for the first
      20 d, individually in metabolism units for the next 3 d, and then in calorimeter
      chambers for the final 5 d with feed intake, feces, and urine excretion measured
      during the final 4 d. Within each period, sex had no effect (P > 0.05) on N or OM
      intake or excretion or N utilization efficiency, with exceptions of steers having
      a greater intake of N (P = 0.036) and OM (P = 0.018) at age of 18 mo and a lower
      ratio of fecal N:N intake (P = 0.023) at age of 6 mo. A range of regression
      relationships (P < 0.05) were developed for prediction of N (g/d) and OM (kg/d)
      excretion in feces and urine. The present data were also used to calculate
      accumulated N and OM intake (kg) and excretion for the 2 sexes. Sex had no
      effects (P > 0.05) on accumulated N or OM intake or N or OM excretion in feces
      and urine or retained N and OM during the first or second year of life. On
      average for the 2 sexes at first and second year of age, the accumulated N
      excretions in feces were 11.4 and 21.1 kg and in urine 11.6 and 30.6 kg,
      respectively, and the corresponding values for accumulated OM excretions were
      respectively 241.5, 565.7, 30.3 and 81.5 kg. A number of equations were developed
      to predict accumulated N and OM excretion in feces and urine (kg) using BW (kg; P
      < 0.001, r(2) = 0.95 to 0.97). The accurate prediction of N and OM excretion in
      feces and urine is essential for reducing N pollution to ground and surface water
      and calculating methane and nitrous oxide emissions from manure management of
      dairy and beef production systems. These data can add novel information to the
      scientific literature and can be used to improve national inventories of manure N
      output and greenhouse gas emissions and to develop appropriate mitigation
      strategies for young Holstein cattle. 

PMID- 24879760
TI  - Influence of thermally oxidized vegetable oils and animal fats on intestinal
      barrier function and immune variables in young pigs.
AB  - To evaluate the effect of feeding thermally oxidized lipids on metabolic
      oxidative status, gut barrier function, and immune response of young pigs, 108
      barrows (6.67 +/- 0.03 kg BW) were assigned to 12 dietary treatments in a 4 * 3
      factorial arrangement in addition to a corn-soybean meal control diet. Main
      effects were 4 lipid sources (corn oil [CN], canola oil [CA], poultry fat [PF],
      and tallow [TL]) and 3 oxidation levels (original lipids [OL], slow oxidation
      [SO] of lipids heated for 72 h at 95 degrees C, or rapid oxidation [RO] of lipids
      heated for 7 h at 185 degrees C). Pigs were provided ad libitum access to diets
      for 28 d followed by controlled feed intake for 10 d. After a 24-h fast on d 38,
      serum was collected and analyzed for alpha-tocopherol (alpha-T), thiobarbituric
      acid reactive substances (TBARS), endotoxin, haptoglobin, IgA, and IgG. On the
      same day following serum collection, lactulose and mannitol were fed and
      subsequently measured in the urine to evaluate gut permeability. There was a
      source * peroxidation interaction for serum alpha-T concentration where pigs fed
      SO or RO had decreased (P < 0.05) serum alpha-T concentration compared with pigs
      fed OL in CA and CN diets but not in pigs fed PF and TL diets. There was no
      source * peroxidation interaction for serum TBARS, but among all lipid sources,
      pigs fed SO or RO lipids had increased (P < 0.05) serum TBARS compared with pigs
      fed OL. In addition, pigs fed CN or CA had greater (P < 0.05) serum TBARS
      compared with pigs fed PF or TL diets. There were no lipid source * peroxidation
      level interaction or lipid source or peroxidation level effects on serum
      endotoxin, haptoglobin, IgA, or IgG. Pigs fed lipid supplemented diets tended to
      have increased serum endotoxin (P = 0.06), IgA (P = 0.10), and IgG (P = 0.09)
      compared with pigs fed the control diet. There were no lipid source *
      peroxidation level interaction or lipid source or peroxidation level effects on
      urinary TBARS and lactulose to mannitol ratio. Compared with pigs fed the control
      diet, pigs fed diets containing lipids had a lower lactulose to mannitol ratio (P
      < 0.01). In conclusion, feeding weaning pigs diets containing 10% thermally
      oxidized lipids for 38 d, especially vegetable oils containing greater
      concentrations of PUFA, appeared to impair oxidative status but had little
      influence on gut barrier function or serum immunity parameters. 

PMID- 24879761
TI  - Incidence, prevalence, severity, and risk factors for ruminal acidosis in feedlot
      steers during backgrounding, diet transition, and finishing.
AB  - The objective of this study was to determine the incidence, prevalence, severity,
      and risk factors for ruminal acidosis in feedlot steers during backgrounding,
      diet transition, and finishing. Steers were purchased from a local auction market
      (n = 250; mean +/- SD; 330 +/- 20.0 kg initial BW) and were grouped together with
      28 steers fitted with a ruminal cannula (248 +/- 25.5 kg initial BW). Steers were
      randomly allocated to 1 of 8 pens (3 to 4 cannulated steers per pen with a total
      of 35 steers/pen). The feeding period (143 d) was divided into 4 phases:
      backgrounding (BKGD; d 1 to 20), diet transition (TRAN; d 21 to 40), and the
      first (FIN1; d 41 to 91) and second half (FIN2; d 92 to 143) of finishing. The
      BKGD diet contained (% DM) barley silage (45.7%), barley grain (41.6%), canola
      meal (4.2%), and a pelleted mineral and vitamin supplement (8.5%). Steers were
      transitioned to a finishing diet containing (% DM) barley silage (5%), barley
      grain (80.9%), canola meal (4.9%), and a pelleted mineral and vitamin supplement
      (9.2%) using 4 transition diets. Feed was offered to achieve 5% refusals (as-is
      basis). Ruminal pH was recorded in cannulated steers every 10 min throughout the
      study, and feed refusals and BW were recorded at 2 wk intervals. Mean ruminal pH
      (P < 0.01) was 6.4, 6.3, 6.2, and 6.0 +/- 0.01 during the BKGD, TRAN, FIN1, and
      FIN2, respectively. The duration (P < 0.01) pH < 5.5 was 4.1, 12.1, 78.7, and 194
      +/- 9.4 min/d during BKGD, TRAN, FIN1, and FIN2, respectively. Using a threshold
      of ruminal pH < 5.5 for at least 180 min to diagnose ruminal acidosis, incidence
      was defined as the number of times steers experienced ruminal acidosis during
      each period and prevalence was defined as the percentage of steers that
      experienced acidosis during each period. On average, the incidence rate (P <
      0.01) of ruminal acidosis was 0.1, 0.3, 6.7, and 14.8 +/- 0.97 episodes during
      BKGD, TRAN, FIN1, and FIN2, respectively. In the same order, the prevalence (P <
      0.01) was 0.7, 1.7, 15.4, and 37.8 +/- 2.0%. Based on multiple regression,
      factors associated with prevalence of ruminal acidosis and the duration pH < 5.5
      were feeding phase (P < 0.01) and DMI (P < 0.01). Overall, the greatest
      incidence, prevalence, and severity of ruminal acidosis were observed towards the
      end of the finishing phase and were associated with days on feed and DMI. 

PMID- 24879762
TI  - Effects of immunological castration and distiller's dried grains with solubles on
      carcass cutability and commercial bacon slicing yields of barrows slaughtered at
      two time points.
AB  - Male pigs were randomly assigned to a castration method at birth and allotted to
      48 pens (28 pigs/pen). Physically castrated (PC) barrows were castrated at 2 d of
      age; immunologically castrated (IC) barrows were administered Improvest (GnRF
      analog diphtheria toxoid conjugate; Zoetis, Kalamazoo, MI) at 16 and 20 wk of
      age. Distiller's dried grains with solubles (DDGS) feeding strategies included
      either 0% DDGS (control), 30% DDGS (30% DDGS) fed from 6 wk of age to slaughter,
      or 30% DDGS fed from 6 wk of age to second dose of Improvest and then fed 0% DDGS
      until slaughter (withdrawal). Four barrows closest to the median pen weight at
      4.5 wk after second dose were selected for evaluation; two were randomly selected
      and slaughtered at 5 wk and the other two at 7 wk after second dose. Data from
      each slaughter time were analyzed independently as a 2 * 3 factorial design with
      pen as the experimental unit. At 5 wk after second dose, bone-in lean cutting
      yields were 2.63% units greater (P < 0.01) in IC when compared to PC. Bellies
      were thicker (P < 0.01) and tended to have greater belly flop distances (P =
      0.07) in PC compared to IC, however iodine values (IV) were not altered (P =
      0.84). Carcass traits (P >= 0.10), cutting yields (P >= 0.43), and fresh belly
      characteristics (P >= 0.08) were minimally affected by DDGS feeding strategy.
      Bacon slicing yields (percentage of green weight) were 6.10% units less (P <
      0.01) in IC compared with PC. At 7 wk after second dose, bone-in lean cutting
      yields were 1.57% units greater (P = 0.03) in IC compared with PC. Distiller's
      grains feeding strategy had no effect (P >= 0.83) on boneless carcass cutting
      yields in IC; while in PC, these yields were 2.32% units less (P < 0.02) in
      control-fed barrows when compared to other feeding strategies (castration method
      * feeding strategy; P = 0.03). Bellies from PC tended to be thicker (P = 0.07)
      and have similar flop distances (P = 0.44) and IV (P = 0.54) when compared with
      IC. Iodine value was greater (P = 0.03) in 30% DDGS-fed barrows compared with
      control-fed barrows. Bacon slicing yields (percentage of green weight) were 4.27%
      units less (P = 0.05) in IC compared with PC. These data suggested that while
      bacon slicing yield was reduced in IC barrows fed control and 30% DDGS compared
      with PC barrow counterparts, withdrawal of DDGS improved bacon slicing yields of
      IC barrows. 

PMID- 24879763
TI  - Struggling to survive: early life challenges in relation to the backtest in pigs.
AB  - Intensively reared piglets may face many early life challenges and these may
      affect behavior. The objective of this study was to examine the relationship
      between piglets' early life circumstances and their behavioral response in a
      backtest. Here, 992 piglets of 14 d of age were subjected to a backtest, in which
      they were restrained for 1 min in a supine position. The number of struggles in
      the backtest was assessed in relation to data on ADG, BW, BW relative to litter
      mates, teat order, litter size, and health. Piglets that had a lower ADG from
      birth until the test day were struggling more (b = -2.4 g ADG/struggle; P =
      0.03). Also, piglets with a lower BW at 14 d of age tended to respond more
      actively in the backtest (b = -0.03 kg/struggle; P = 0.08). The response to the
      backtest was unrelated to ADG from birth until weaning, birth weight, weaning
      weight, teat order, litter size, and health. ADG and BW were unrelated to the
      variation of backtest responses within the litter. The weak though significant
      relationship suggests that smaller, slower-growing piglets more actively respond
      to a challenge, either because piglets born with such a behavioral response were
      better able to survive, or because piglets adapted their behavioral response to
      their physical condition. 

PMID- 24879764
TI  - Genetic analysis of reproductive traits and antibody response in a PRRS outbreak
      herd.
AB  - Porcine reproductive and respiratory syndrome (PRRS) is the most economically
      significant disease impacting pig production in North America, Europe, and Asia,
      causing reproductive losses such as increased rates of stillbirth and mummified
      piglets. The objective of this study was to explore the genetic basis of host
      response to the PRRS virus (PRRSV) in a commercial multiplier sow herd before and
      after a PRRS outbreak, using antibody response and reproductive traits.
      Reproductive data comprising number born alive (NBA), number alive at 24 h
      (NA24), number stillborn (NSB), number born mummified (NBM), proportion born dead
      (PBD), number born dead (NBD), number weaned (NW), and number of mortalities
      through weaning (MW) of 5,227 litters from 1,967 purebred Landrace sows were used
      along with a pedigree comprising 2,995 pigs. The PRRS outbreak date was estimated
      from rolling averages of farrowing traits and was used to split the data into a
      pre-PRRS phase and a PRRS phase. All 641 sows in the herd during the outbreak
      were blood sampled 46 d after the estimated outbreak date and were tested for
      anti-PRRSV IgG using ELISA (sample-to-positive [S/P] ratio). Genetic parameters
      of traits were estimated separately for the pre-PRRS and PRRS phase data sets.
      Sows were genotyped using the PorcineSNP60 BeadChip, and genome-wide association
      studies (GWAS) were performed using method Bayes B. Heritability estimates for
      reproductive traits ranged from 0.01 (NBM) to 0.12 (NSB) and from 0.01 (MW) to
      0.12 (NBD) for the pre-PRRS and PRRS phases, respectively. S/P ratio had
      heritability (0.45) and strong genetic correlations with most traits, ranging
      from -0.72 (NBM) to 0.73 (NBA). In the pre-PRRS phase, regions associated with
      NSB and PBD explained 1.6% and 3% of the genetic variance, respectively. In the
      PRRS phase, regions associated with NBD, NSB, and S/P ratio explained 0.8%, 11%,
      and 50.6% of the genetic variance, respectively. For S/P ratio, 2 regions on SSC
      7 (SSC7) separated by 100 Mb explained 40% of the genetic variation, including a
      region encompassing the major histocompatibility complex, which explained 25% of
      the genetic variance. These results indicate a significant genomic component
      associated with PRRSV antibody response and NSB in this data set. Also, the high
      heritability and genetic correlation estimates for S/P ratio during the PRRS
      phase suggest that S/P ratio could be used as an indicator of the impact of PRRS
      on reproductive traits. 

PMID- 24879765
TI  - Effects of temperature-humidity index and chromium supplementation on antioxidant
      capacity, heat shock protein 72, and cytokine responses of lactating cows.
AB  - Heat stress adversely affects the productivity and immune status of dairy cows.
      The temperature-humidity index (THI) is commonly used to indicate the degree of
      heat stress on dairy cattle. We investigated the effects of different THI and Cr
      supplementation on the antioxidant capacity, the levels of heat shock protein 72
      (Hsp72), and cytokine responses of lactating cows. The study used a total of 24
      clinically healthy uniparous midlactation Holstein cows, which were randomly
      divided into 2 groups (n = 12 per group), and was conducted in 3 designated THI
      periods: low THI period (LTHI; THI = 56.4 +/- 2.5), moderate THI period (MTHI;
      THI = 73.9 +/- 1.7), and high THI period (HTHI; THI = 80.3 +/- 1.0). The 2 groups
      of cows were fed corn and corn silage based basal diet supplemented chromium
      picolinate to provide 3.5 mg of Cr/cow daily (Cr+) or basal diet with no Cr (Cr
      ). The experiment was a 3 * 2 factorial design. The numbers of leukocytes (P <
      0.05) and serum levels of glucose (P < 0.001) were lower; however, the serum
      levels of blood urea nitrogen (BUN; P < 0.001) and creatinine (P < 0.001) were
      greater in the MTHI and HTHI than in LTHI. The total antioxidant capacity in the
      serum was unaltered; an increase in superoxide dismutase activity (P < 0.001) and
      in serum malondialdehyde concentration (P < 0.001) was observed in the MTHI and
      HTHI compared with the LTHI. The high THI led to increases in serum
      concentrations of tumor necrosis factor-alpha (TNF-alpha; P < 0.001) and IL-10 (P
      < 0.05). Cows supplemented with Cr had lower (P = 0.009) serum concentrations of
      cholesterol but greater (P < 0.001, respectively) serum levels of Hsp72 and IL-10
      compared with those without Cr supplementation in the HTHI. Western blot analysis
      revealed that cows supplemented with Cr had greater (P = 0.038) expression of the
      inhibitor of nuclear factor kappa B alpha (IkappaBalpha) in peripheral blood
      mononuclear cells (PBMC) compared with those without Cr supplementation in the
      HTHI, whereas the expression of Hsp72 in PBMC was unaltered. Data indicate that
      there is a decrease in glucose and increases in BUN and creatinine in the serum
      of midlactation cows under hot conditions during the summer and that these cows
      have a lowered oxidative capacity but an elevated antioxidant capacity. In
      addition, Cr may play an anti-inflammatory role in lactating cows by promoting
      the release of Hsp72, increasing the production of IL-10, and inhibiting the
      degradation of IkappaBalpha under hot conditions during the summer. 

PMID- 24879767
TI  - Use of a stair-step compensatory gain nutritional regimen to program the onset of
      puberty in beef heifers.
AB  - It was hypothesized that metabolic programming of processes underlying puberty
      can be shifted temporally through the use of a stair-step compensatory growth
      model such that puberty is optimally timed to occur at 11 to 12 mo of age. Forty
      crossbred beef heifers were weaned at approximately 3.5 mo of age and, after a 2
      wk acclimation period, were assigned randomly to 1 of 4 nutritional groups: 1)
      low control (LC), restricted feed intake of a forage-based diet to promote BW
      gain of 0.5 kg/d until 14 mo of age, 2) high control (HC), controlled feed intake
      of a high-concentrate diet to promote BW gain of 1 kg/d until 14 mo of age, 3)
      stair-step 1 (SS-1), ad libitum feed intake of a high-concentrate diet until 6.5
      mo of age followed by restricted access to a high-forage diet to promote BW gain
      of 0.35 kg/d until 9 mo of age, ad libitum feed intake of a high-concentrate diet
      until 11.5 mo of age, and restricted intake of a high-forage diet to promote BW
      gain of 0.35 kg/d until 14 mo of age, and 4) stair-step 2 (SS-2), reverse
      sequence of SS-1, beginning with restricted access to a high-forage diet. Body
      weight (every 2 wk) and circulating concentrations of leptin (monthly) were
      determined throughout the experiment. Concentrations of progesterone in blood
      samples collected twice weekly beginning at 8 mo of age were used to determine
      pubertal status. Body weight gain followed a pattern similar to that proposed in
      our experimental design. Circulating concentrations of leptin increased following
      distinct elevations in BW but decreased abruptly after feed intake restriction.
      Survival analysis indicated that the percentage of pubertal heifers in the LC
      group was lower (P < 0.05) than all other groups throughout the experiment.
      Although heifers in SS-1 were nutritionally restricted between 6.5 and 9 mo of
      age, the proportion pubertal by 12 mo of age did not differ (P = 0.36) from that
      of the HC group, with 80% and 70% pubertal in SS-1 and HC, respectively. In
      contrast, the proportion of heifers pubertal by 12 mo of age in the SS-2 group
      (40%) was lower (P < 0.05) than both HC and SS-1. However, by 14 mo of age, 90%
      of heifers in the SS-2 group had also attained puberty compared to only 40% of
      the LC group. In summary, these data provide evidence that changes in the
      nutritional and metabolic status during the early juvenile period can program the
      onset of puberty that occurs months later, allowing optimal timing of sexual
      maturation in replacement beef heifers. 

PMID- 24879766
TI  - Genetic evaluation of aspects of temperament in Nellore-Angus calves.
AB  - The objective of this work was to estimate heritability of each of 5 subjectively
      measured aspects of temperament of cattle and the genetic correlations of pairs
      of those traits. From 2003 to 2013, Nellore-Angus F2 and F3 calves (n = 1,816)
      were evaluated for aspects of temperament at an average 259 d of age, which was
      approximately 2 mo after weaning. Calves were separated from a group and
      subjectively scored from 1 (calm, good temperament) to 9 (wild, poor temperament)
      for aggressiveness (willingness to hit an evaluator), nervousness, flightiness,
      gregariousness (willingness to separate from the group), and a distinct overall
      score by 4 evaluators. Data were analyzed using threshold and linear models with
      additive genetic random effects. Two-trait animal models (nonthreshold) included
      the additive genetic covariance for pairs of traits and were used to estimate
      additive genetic correlations. Contemporary groups (n = 104) represented calves
      penned together for evaluation on given evaluation days. Heifers had greater
      (worse) means for all traits than steers (P < 0.05). The regression of score on
      age in days was included in final models for flightiness (P = 0.05; -0.006 +/-
      0.003) and gregariousness (P = 0.025; -0.007 +/- 0.003). Estimates of
      heritability were large (0.51, 0.4, 0.45, 0.49, and 0.47 for aggressiveness,
      nervousness, flightiness, gregariousness, and overall temperament, respectively;
      SE = 0.07 for each). The ability to use this methodology to distinctly separate
      different aspects of calf temperament appeared to be limited, as estimates of
      additive genetic correlations were near unity for all pairs of traits; estimates
      of phenotypic correlation ranged from 0.88 +/- 0.01 to 0.99 +/- 0.002 for pairs
      of traits. Distinct subsequent analyses indicated a significant negative
      relationship of 4 of the various temperament scores with weight at weaning
      (regression coefficients ranged from -0.008 +/- 0.002 for nervousness,
      flightiness, and gregariousness to -0.003 +/- 0.002 for aggressiveness). In
      subsequent analyses, the regression of temperament trait on sequence of
      evaluation within a pen was highly significant and solutions ranged from 0.05 +/-
      0.007 for aggressiveness to 0.08 +/- 0.007 for all other traits. The apparent
      large additive genetic variance for any one of these traits may be useful in
      identification of genes responsible for differences in cattle temperament. 

PMID- 24879768
TI  - Stem extension and mechanical stability of Xanthium canadense grown in an open or
      in a dense stand.
AB  - BACKGROUND AND AIMS: Plants in open, uncrowded habitats typically have relatively
      short stems with many branches, whereas plants in crowded habitats grow taller
      and more slender at the expense of mechanical stability. There seems to be a
      trade-off between height growth and mechanical stability, and this study
      addresses how stand density influences stem extension and consequently plant
      safety margins against mechanical failure. METHODS: Xanthium canadense plants
      were grown either solitarily (S-plants) or in a dense stand (D-plants) until
      flowering. Internode dimensions and mechanical properties were measured at the
      metamer level, and the critical buckling height beyond which the plant
      elastically buckles under its own weight and the maximum lateral wind force the
      plant can withstand were calculated. KEY RESULTS: Internodes were longer in D-
      than S-plants, but basal diameter did not differ significantly. Relative growth
      rates of internode length and diameter were negatively correlated to the
      volumetric solid fraction of the internode. Internode dry mass density was higher
      in S- than D-plants. Young's modulus of elasticity and the breaking stress were
      higher in lower metamers, and in D- than in S-plants. Within a stand, however,
      both moduli were positively related to dry mass density. The buckling safety
      factor, a ratio of critical buckling height to actual height, was higher in S-
      than in D-plants. D-plants were found to be approaching the limiting value 1.
      Lateral wind force resistance was higher in S- than in D-plants, and increased
      with growth in S-plants. CONCLUSIONS: Critical buckling height increased with
      height growth due mainly to an increase in stem stiffness and diameter and a
      reduction in crown/stem mass ratio. Lateral wind force resistance was enhanced
      due to increased tissue strength and diameter. The increase in tissue stiffness
      and strength with height growth plays a crucial role in maintaining a safety
      margin against mechanical failure in herbaceous species that lack the capacity
      for secondary growth.

PMID- 24879769
TI  - In adolescence, extreme prematurity is associated with significant changes in the
      microvasculature, elevated blood pressure and increased carotid intima-media
      thickness.
AB  - OBJECTIVES: Increased carotid intima-media thickness (cIMT) and loss of capillary
      density are antecedents of cardiovascular disease in adults. Former preterm
      infants are at risk for metabolic precursors of vascular disease, but vascular
      changes have not yet been studied in this population. PATIENTS AND METHODS: In 54
      former preterm (birth weigh (BW) 753+/-152 g) and 12 term children (BW 3395+/-558
      g), functional vessel density (FVD) on the forearm and cIMT were obtained at a
      mean (+/-SD) age of 11.8+/-1.5 years. FVD was measured using sidestream dark
      field imaging before, during and after arterial occlusion, and cIMT using high
      resolution B-mode ultrasonography. Statistical comparisons were made using the t
      test, Mann-Whitney U test and the sign test for symmetry, with a two-sided p
      value as appropriate. RESULTS: The systolic blood pressure of the former preterm
      children was significantly increased compared to reference values (females 119+/
      8, z score 1.23; males 118+/-11, z score 1.14 mm Hg), as were the cIMT values
      (0.45+/-0.03 mm vs 0.38+/-0.04 mm; p<0.001). FVD was significantly higher in
      former preterm children compared to controls at baseline (mean+/-SD 33.6+/-14.5
      cm/cm(2) vs 23.0+/-7.1 cm/cm(2); p=0.002) with decreased reactivity during
      arterial occlusion (chi(2) 7.14, p=0.008). CONCLUSIONS: Preterm birth is
      associated with significant permanent alteration in the microcirculation and
      increased cIMT and systolic blood pressure. It is unknown whether these changes
      are due to preterm birth and rapid maturation of the skin or to nutritional
      factors, as previously thought. This is an important area of future research.

PMID- 24879771
TI  - Editorial.

PMID- 24879773
TI  - Longevity and healthy ageing - Will healthcare be drowned by the grey Tsunami or
      sunk by the demographic iceberg?
AB  - Will healthcare be drowned by the grey Tsunami or sunk by the demographic
      iceberg? Or will new and radical, economic, medical, nutritional, exercise and
      life style developments, produce a better economic model for future healthcare. A
      properly funded Health Service rather than an over Politicised Failing Sickness
      service.

PMID- 24879770
TI  - Aquaporin-mediated increase in root hydraulic conductance is involved in silicon
      induced improved root water uptake under osmotic stress in Sorghum bicolor L.
AB  - The fact that silicon application alleviates water deficit stress has been widely
      reported, but the underlying mechanism remains unclear. Here the effects of
      silicon on water uptake and transport of sorghum seedlings (Sorghum bicolor L.)
      growing under polyethylene glycol-simulated osmotic stress in hydroponic culture
      and water deficit stress in sand culture were investigated. Osmotic stress
      dramatically decreased dry weight, photosynthetic rate, transpiration rate,
      stomatal conductance, and leaf water content, but silicon application reduced
      these stress-induced decreases. Although silicon application had no effect on
      stem water transport capacity, whole-plant hydraulic conductance (Kplant) and
      root hydraulic conductance (Lp) were higher in silicon-treated seedlings than in
      those without silicon treatment under osmotic stress. Furthermore, the extent of
      changes in transpiration rate was similar to the changes in Kplant and Lp. The
      contribution of aquaporin to Lp was characterized using the aquaporin inhibitor
      mercury. Under osmotic stress, the exogenous application of HgCl2 decreased the
      transpiration rates of seedlings with and without silicon to the same level;
      after recovery induced by dithiothreitol (DTT), however, the transpiration rate
      was higher in silicon-treated seedlings than in untreated seedlings. In addition,
      transcription levels of several root aquaporin genes were increased by silicon
      application under osmotic stress. These results indicate that the silicon-induced
      up-regulation of aquaporin, which was thought to increase Lp, was involved in
      improving root water uptake under osmotic stress. This study also suggests that
      silicon plays a modulating role in improving plant resistance to osmotic stress
      in addition to its role as a mere physical barrier. 

PMID- 24879774
TI  - Future prospects for longevity.
AB  - It is acknowledged that the world is ageing at both the individual and population
      level. Life expectancies at birth have increased for males and females in the
      more developed economies across the 20th century. The 21st century is expected to
      see this development continue with life expectancies moving towards 100 years.
      This paper looks at the evidence for future increases in life expectancy and for
      the longest-lived to live even longer.

PMID- 24879775
TI  - Can restricting calories help you to live longer?
AB  - Excess calorie consumption is associated with metabolic disorders and increased
      incidence of morbidity. Restricting calorie content, either by daily calorie
      restriction or intermittent fasting periods, has multiple benefits including
      weight loss and improved body composition. Previous research has shown that
      restricting calories in this way can increase longevity and slow the ageing
      process in laboratory animals, although only sparse data exist in human
      populations. This review critically evaluates the benefits of these dietary
      interventions on age-related decline and longevity.

PMID- 24879776
TI  - Sarcopenia, malnutrition and nutrient density in older people.
AB  - Both sarcopenia and malnutrition can have a significant impact on health and
      functional status in older people. Good nutrition and physical activity
      throughout life are protective factors. In addition to inadequate nutrient
      intake, reduced physical activity is known to increase the risk of developing
      sarcopenia. Progressive resistance training has been shown to be an effective
      intervention and there is also significant potential for whole diet
      interventions, many of which are also effective in treating malnutrition.

PMID- 24879777
TI  - Maintaining sexuality in menopause.
AB  - Sexual health in the menopause is a medical challenge because the progressive
      decline of sexual hormones interacts with the aging process and many psychosocial
      stressors modulate vulnerability for sexual symptoms (low sexual desire, poor
      arousal and lubrication, dyspareunia, orgasmic dysfunction and lack of
      satisfaction). In clinical practice, a coordinated approach is needed to
      optimally manage the risk for developing female sexual dysfunction (FSD),
      especially when chronic conditions are present. Biomedical and psychosocial
      interventions include general education, recognition of signs and symptoms,
      promotion of health, attention to the partner and individualization of treatment.
      Counselling to overcome personal and relational difficulties should be always
      combined with hormonal and non-hormonal strategies to maximize biological signals
      driving the sexual response. By enhancing women's abilities to cope with sexual
      changes at midlife, health care providers may significantly optimize healthy
      aging and partnership.

PMID- 24879779
TI  - Evaluation of gabapentin in management of hot flushes in postmenopausal women.
AB  - This study was conducted to assess the efficacy of gabapentin in controlling hot
      flushes in postmenopausal women. Fifty postmenopausal patients with hot flushes
      were randomized in two groups, one receiving gabapentin 900 mg daily along with
      calcium and another group receiving calcium alone. Frequency, duration and
      severity of hot flushes were noted and a composite score was calculated. There
      was around an 80% reduction in composite score in the gabapentin group at 3 and 6
      months; significantly more than the placebo group. Gabapentin has a two-fold
      better response than placebo in reducing hot flushes with the relief starting
      from the first month and maximum effect at 3 months.

PMID- 24879778
TI  - Management of prolapse in older women.
AB  - Pelvic organ prolapse (POP) is a common problem affecting 37% of women over the
      age of 80. Review by a specialist with the aid of a validated quality of life
      questionnaire will help assess bother, as well as the frequency and severity of
      urinary, bowel and sexual symptoms. Pelvic examination should be carried out to
      assess the extent of any prolapse and the compartments affected. The main aim of
      the treatment is to improve the woman's quality of life. Treatment options may be
      conservative with lifestyle modifications and pelvic floor muscle therapy, use of
      a pessary or surgery. Treatment has previously been incorrectly limited in the
      elderly with the misconception that surgery should be avoided. Her current state
      of health and expectations are most important. Regardless of age, each patient
      should be assessed individually with a holistic multi-compartment approach and
      the risk benefit ratios of every treatment considered.

PMID- 24879780
TI  - Practice observed.

PMID- 24879781
TI  - Third-degree heart block associated with lyme carditis: review of published
      cases.
AB  - Lyme carditis is an uncommon manifestation of Lyme disease that most commonly
      involves some degree of atrioventricular conduction blockade. Third-degree
      conduction block is the most severe form and can be fatal if untreated.
      Systematic review of the medical literature identified 45 published cases of
      third-degree conduction block associated with Lyme carditis in the United States.
      Median patient age was 32 years, 84% of patients were male, and 39% required
      temporary pacing. Recognizing patient groups more likely to develop third-degree
      heart block associated with Lyme carditis is essential to providing prompt and
      appropriate therapy. 

PMID- 24879782
TI  - Lyme disease testing by large commercial laboratories in the United States.
AB  - BACKGROUND: Laboratory testing is helpful when evaluating patients with suspected
      Lyme disease (LD). A 2-tiered antibody testing approach is recommended, but
      single-tier and nonvalidated tests are also used. We conducted a survey of large
      commercial laboratories in the United States to assess laboratory practices. We
      used these data to estimate the cost of testing and number of infections among
      patients from whom specimens were submitted. METHODS: Large commercial
      laboratories were asked to report the type and volume of testing conducted
      nationwide in 2008, as well as the percentage of positive tests for 4 LD-endemic
      states. The total direct cost of testing was calculated for each test type. These
      data and test-specific performance parameters available in published literature
      were used to estimate the number of infections among source patients. RESULTS:
      Seven participating laboratories performed approximately 3.4 million LD tests on
      approximately 2.4 million specimens nationwide at an estimated cost of $492
      million. Two-tiered testing accounted for at least 62% of assays performed;
      alternative testing accounted for <3% of assays. The estimated frequency of
      infection among patients from whom specimens were submitted ranged from 10% to
      18.5%. Applied to the total numbers of specimens, this yielded an estimated 240
      000 to 444 000 infected source patients in 2008. DISCUSSION: LD testing is common
      and costly, with most testing in accordance with diagnostic recommendations.
      These results highlight the importance of considering clinical and exposure
      history when interpreting laboratory results for diagnostic and surveillance
      purposes.

PMID- 24879784
TI  - Optimizing urine culture collection in the emergency department using frontline
      ownership interventions.

PMID- 24879783
TI  - Staphylococcus aureus bacteremia at 5 US academic medical centers, 2008-2011:
      significant geographic variation in community-onset infections.
AB  - BACKGROUND: The incidence of community-onset (CO) methicillin-resistant
      Staphylococcus aureus (MRSA) bacteremia rose from the late 1990s through the
      2000s. However, hospital-onset (HO) MRSA rates have recently declined in the
      United States and Europe. METHODS: Data were abstracted from infection prevention
      databases between 1 January 2008 and 31 December 2011 at 5 US academic medical
      centers to determine the number of single-patient blood cultures positive for
      MRSA and methicillin-susceptible S. aureus (MSSA) per calendar year, stratified
      into CO and HO infections. RESULTS: Across the 5 centers, 4171 episodes of
      bacteremia were identified. Center A (Los Angeles, California) experienced a
      significant decline in CO-MRSA bacteremia rates (from a peak in 2009 of 0.42 to
      0.18 per 1000 patient-days in 2011 [P = .005]), whereas CO-MSSA rates remained
      stable. Centers B (San Francisco, California), D (Chicago, Illinois), and E
      (Raleigh-Durham, North Carolina) experienced a stable incidence of CO-MRSA and CO
      MSSA bacteremia. In contrast, at center C (New York, New York), the incidence of
      CO-MRSA increased >3-fold (from 0.11 to 0.34 cases per 1000 patient-days [P <
      .001]). At most of the sites, HO-MRSA decreased and HO-MSSA rates were stable.
      USA300 accounted for 52% (104/202) of genotyped MRSA isolates overall, but this
      varied by center, ranging from 35% to 80%. CONCLUSIONS: CO-MRSA rates and the
      contribution of USA300 MRSA varied dramatically across diverse geographical areas
      in the United States. Enhanced infection control efforts are unlikely to account
      for such variation in CO infection rates. Bioecological and clinical explanations
      for geographical differences in CO-MRSA bacteremia rates merit further study.

PMID- 24879785
TI  - FKS mutant Candida glabrata: risk factors and outcomes in patients with
      candidemia.
AB  - BACKGROUND: Echinocandins are recommended for Candia glabrata candidemia.
      Mutations in the FKS1 and FKS2 genes are associated with echinocandin resistance.
      Few studies have assessed risk factors for FKS mutant isolates and outcomes in
      patients receiving micafungin treatment. METHODS: Patients with C. glabrata
      bloodstream infection admitted to a large, tertiary care hospital between 2009
      and 2012 were included in this study. For each isolate, FKS1 and FKS2 genes were
      sequenced to identify mutations. Risk factors for FKS mutations and treatment
      outcomes in patients receiving an echinocandin were assessed using multivariate
      logistic regression. RESULTS: Seventy-two patients were included in the study of
      which 13 (18%) had an FKS mutant isolate. The only significant predictor for FKS
      mutations was prior echinocandin exposure (odds ratio [OR], 19.9; 95% confidence
      interval [CI], 4.7-84.7; P <= .01). Treatment failure occurred in 17 (30%) of 57
      patients who received an echinocandin and was more common in patients with FKS
      mutants (6 of 10; 60%) compared with non-FKS mutants (11 of 47; 23%). Underlying
      gastrointestinal disorder (OR, 4.7; 95% CI, 1.1-20.9; P = .04) and prior
      echinocandin exposure (OR, 8.3; 95% CI, 1.7-40.4; P <= .01) were independent
      predictors of echinocandin treatment failure. Treatment response and echinocandin
      minimum inhibitory concentrations varied among specific FKS mutations.
      CONCLUSIONS: FKS mutations were identified in 18% of 72 patients with C. glabrata
      candidemia. Common risk factors for FKS mutant isolates included previous
      echinocandin exposure, which also influenced response rates.

PMID- 24879786
TI  - Antigen-specific B-cell response to 13-valent pneumococcal conjugate vaccine in
      asplenic individuals with beta-thalassemia previously immunized with 23-valent
      pneumococcal polysaccharide vaccine.
AB  - Current guidelines recommend a combined schedule of a 13-valent pneumococcal
      conjugate vaccine (PCV13) and PPSV23 (23-valent polysaccharide vaccine) for
      asplenic individuals. We show that PCV13 induces a T-dependent immune response in
      asplenic individuals with beta-thalassemia, but previous PPSV23s affect the
      memory B-cell response in a dose- and time-dependent manner. Clinical Trials
      Registration. NCT01846923. 

PMID- 24879787
TI  - Reply to Chironda et Al.

PMID- 24879788
TI  - Improved prediction of salvage antiretroviral therapy outcomes using
      ultrasensitive HIV-1 drug resistance testing.
AB  - BACKGROUND: The clinical relevance of ultrasensitive human immunodeficiency virus
      type 1 (HIV-1) genotypic resistance testing in antiretroviral treatment (ART)
      experienced individuals remains unknown. METHODS: This was a retrospective,
      multicentre, cohort study in ART-experienced, HIV-1-infected adults who initiated
      salvage ART including, at least 1 ritonavir-boosted protease inhibitor,
      raltegravir or etravirine. Presalvage ART Sanger and 454 sequencing of plasma HIV
      1 were used to generate separate genotypic sensitivity scores (GSS) using the
      HIVdb, ANRS, and REGA algorithms. Virological failure (VF) was defined as 2
      consecutive HIV-1 RNA levels >=200 copies/mL at least 12 weeks after salvage ART
      initiation, whereas subjects remained on the same ART. The ability of Sanger and
      454-GSS to predict VF was assessed by receiver operating characteristic (ROC)
      curves and survival analyses. RESULTS: The study included 132 evaluable subjects;
      28 (21%) developed VF. Using HIVdb, 454 predicted VF better than Sanger
      sequencing in the ROC curve analysis (area under the curve: 0.69 vs 0.60, Delong
      test P = .029). Time to VF was shorter for subjects with 454-GSS < 3 vs 454-GSS
      >= 3 (Log-rank P = .003) but not significantly different between Sanger-GSS < 3
      and >=3. Factors independently associated with increased risk of VF in
      multivariate Cox regression were a 454-GSS < 3 (HR = 4.6, 95 CI, [1.5, 14.0], P =
      .007), and the number of previous antiretrovirals received (HR = 1.2 per
      additional drug, 95 CI, [1.1, 1.3], P = .001). Equivalent findings were obtained
      with the ANRS and REGA algorithms. CONCLUSIONS: Ultrasensitive HIV-1 genotyping
      improves GSS-based predictions of virological outcomes of salvage ART relative to
      Sanger sequencing. This may improve the clinical management of ART-experienced
      subjects living with HIV-1. CLINICAL TRIALS REGISTRATION: NCT01346878.

PMID- 24879789
TI  - Noninducibility in postinfarction ventricular tachycardia as an end point for
      ventricular tachycardia ablation and its effects on outcomes: a meta-analysis.
AB  - BACKGROUND: Although ventricular tachycardia (VT) ablation is a widely used
      therapy for patients with VT, the ideal end points for this procedure are not
      well defined. We performed a meta-analysis of the published literature to assess
      the predictive value of noninducibility of postinfarction VT for long-term
      outcomes after VT ablation. METHODS AND RESULTS: We performed a systematic review
      of MEDLINE (1950-2013), EMBASE (1988-2013), the Cochrane Controlled Trials
      Register (Fourth Quarter, 2012), and reports presented at scientific meetings
      (1994-2013). Randomized controlled trials, case-control, and cohort studies of VT
      ablation were included. Outcomes reported in eligible studies were freedom from
      VT/ventricular fibrillation and all-cause mortality. Of the 3895 studies
      evaluated, we identified 8 cohort studies enrolling 928 patients for the meta
      analysis. Noninducibility after VT ablation was associated with a significant
      increase in arrhythmia-free survival compared with partial success (odds ratio,
      0.49; 95% confidence interval, 0.29-0.84; P=0.009) or failed ablation procedure
      (odds ratio, 0.10; 95% confidence interval, 0.06-0.18; P<0.001). There was also a
      significant reduction in all-cause mortality if patients were noninducible after
      VT ablation compared with patients with partial success (odds ratio, 0.59; 95%
      confidence interval, 0.36-0.98; P=0.04) or failed ablation (odds ratio, 0.32; 95%
      confidence interval, 0.10-0.99; P=0.049). CONCLUSIONS: Noninducibility of VT
      after VT ablation is associated with improved arrhythmia-free survival and all
      cause mortality.

PMID- 24879790
TI  - Binding of AID to DNA does not correlate with mutator activity.
AB  - The DNA deaminase activation-induced cytidine deaminase (AID) initiates somatic
      hypermutation (SHM) and class switch recombination (CSR) by deaminating cytidines
      to uridines at V region (V) genes and switch (S) regions. The mechanism by which
      AID is recruited to V genes and S region DNA is poorly understood. In this study,
      we used the CH12 B lymphoma line to demonstrate that, although S regions can
      efficiently recruit AID and undergo mutations and deletions, AID neither binds to
      nor mutates the V gene, thus clearly demonstrating intraimmunoglobulin locus
      specificity. Depletion of the RNA-binding protein polypyrimidine tract binding
      protein-2, previously shown to promote recruitment of AID to S regions, enables
      stable association of AID with the V gene. Surprisingly, AID binding to the V
      gene does not induce SHM. These results unmask a striking lack of correlation
      between AID binding and its mutator activity, providing evidence for the presence
      of factors required downstream of AID binding to effect SHM. Furthermore, our
      findings suggest that S regions are preferred targets for AID and, aided by
      polypyrimidine tract binding protein-2, act as "sinks" to sequester AID activity
      from other genomic regions. 

PMID- 24879791
TI  - A critical role for human caspase-4 in endotoxin sensitivity.
AB  - Response to endotoxins is an important part of the organismal reaction to Gram
      negative bacteria and plays a critical role in sepsis and septic shock, as well
      as other conditions such as metabolic endotoxemia. Humans are generally more
      sensitive to endotoxins when compared with experimental animals such as mice.
      Inflammatory caspases mediate endotoxin-induced IL-1beta secretion and lethality
      in mice, and caspase-4 is an inflammatory caspase that is found in the human, and
      not mouse, genome. To test whether caspase-4 is involved in endotoxin
      sensitivity, we developed a transgenic mouse expressing human caspase-4 in its
      genomic context. Caspase-4 transgenic mice exhibited significantly higher
      endotoxin sensitivity, as measured by enhanced cytokine secretion and lethality
      following LPS challenge. Using bone marrow-derived macrophages, we then observed
      that caspase-4 can support activation of caspase-1 and secretion of IL-1beta and
      IL-18 in response to priming signals (LPS or Pam3CSK4) alone, without the need
      for second signals to stimulate the assembly of the inflammasome. These findings
      indicate that the regulation of caspase-1 activity by human caspase-4 could
      represent a unique mechanism in humans, as compared with laboratory rodents, and
      may partially explain the higher sensitivity to endotoxins observed in humans.
      Regulation of the expression, activation, or activity of caspase-4 therefore
      represents targets for systemic inflammatory response syndrome, sepsis, septic
      shock, and related disorders. 

PMID- 24879792
TI  - BCL6 controls Th9 cell development by repressing Il9 transcription.
AB  - The transcriptional repressor B cell lymphoma 6 (BCL6) is required for the
      development of Th follicular cells, and it has been shown to suppress Th2 cell
      differentiation. We demonstrate that BCL6 is a key regulator of Th9 cell
      development. BCL6 expression is transiently downregulated in polarized Th9 cells,
      and forced expression of BCL6 in Th9 cells impairs Th9 cell differentiation. In
      contrast, BCL6 knockdown upregulated IL-9 production in Th9 cells. The function
      of BCL6 in Th9 cells is under the control of IL-2/JAK3/STAT5 signaling pathway.
      Using chromatin immunoprecipitation, we show that, in Th9 cells, BCL6 and STAT5
      bind to adjacent motifs in the Il9 promoter. Furthermore, we found that STAT5
      binding was associated with the abundance of a permissive histone mark at the Il9
      promoter, whereas under conditions in which BCL6 binding was predominant, a
      repressive histone mark was prevalent. The effects of STAT5 and BCL6 on IL-9
      transcription were further demonstrated using an IL-9 luciferase reporter assay
      in which BCL6 repressed STAT5-mediated Il9 transactivation. In experimental
      autoimmune encephalomyelitis, forced expression of BCL6 in myelin oligodendrocyte
      glycoprotein35-55-specific Th9 cells resulted in decreased IL-9 production and
      induction of IFN-gamma, causing an exacerbation of the clinical disease. Our
      findings demonstrate a novel role of BCL6 in the regulation of Th9 cell
      development and their encephalitogenicity. 

PMID- 24879793
TI  - Endogenously expressed IL-13Ralpha2 attenuates IL-13-mediated responses but does
      not activate signaling in human lung fibroblasts.
AB  - IL-13 can bind to two distinct receptors: a heterodimer of IL-13Ralpha1/IL
      4Ralpha and IL-13Ralpha2. Whereas IL-13Ralpha1/IL-4Ralpha engagement by IL-13
      leads to the activation of STAT6, the molecular events triggered by IL-13 binding
      to IL-13Ralpha2 remain incompletely understood. IL-4 can bind to and signal
      through the IL-13Ralpha1/IL-4Ralpha complex but does not interact with IL
      13Ralpha2. Idiopathic pulmonary fibrosis is a progressive and generally fatal
      parenchymal lung disease of unknown etiology with no current pharmacologic
      treatment options that substantially prolong survival. Preclinical models of
      fibrotic diseases have implicated IL-13 activity on multiple cell types,
      including macrophages and fibroblasts, in initiating and perpetuating
      pathological fibrosis. In this study, we show that IL-13, IL-4, IL-13Ralpha2, and
      IL-13-inducible target genes are expressed at significantly elevated levels in
      lung tissue from patients with idiopathic pulmonary fibrosis compared with
      control lung tissue. IL-4 and IL-13 induce virtually identical transcriptional
      responses in human monocytes, macrophages, and lung fibroblasts. IL-13Ralpha2
      expression can be induced in lung fibroblasts by IL-4 or IL-13 via a STAT6
      dependent mechanism, or by TNF-alpha via a STAT6-independent mechanism.
      Endogenously expressed IL-13Ralpha2 decreases, but does not abolish, sensitivity
      of lung fibroblasts to IL-13 and does not affect sensitivity to IL-4. Genome-wide
      transcriptional analyses of lung fibroblasts stimulated with IL-13 in the
      presence of Abs that selectively block interactions of IL-13 with IL-13Ralpha1/IL
      4Ralpha or IL-13Ralpha2 show that endogenously expressed IL-13Ralpha2 does not
      activate any unique IL-13-mediated gene expression patterns, confirming its role
      as a decoy receptor for IL-13 signaling. 

PMID- 24879795
TI  - The thyroxine-containing thyroglobulin peptide (aa 2549-2560) is a target epitope
      in iodide-accelerated spontaneous autoimmune thyroiditis.
AB  - Enhanced iodide ingestion is known to accelerate the incidence and severity of
      spontaneous autoimmune thyroiditis [iodide-accelerated spontaneous autoimmune
      thyroiditis (ISAT)] in NOD.H2(h4) mice. CD4+ cells are required for the
      development and maintenance of ISAT, but their target epitopes remain unknown. In
      this study, we show that the previously identified thyroglobulin (Tg) T cell
      epitope p2549-2560 containing thyroxine at position 2553 (T4p2553) induces
      thyroiditis as well as strong specific T and B cell responses in NOD.H2(h4) mice.
      In ISAT, activated CD4+ T cells specific for T4p2553 are detected before the
      disease onset in thyroid-draining cervical lymph nodes only in mice placed on an
      iodide-rich diet and not in age-matched controls. In addition, selective
      enrichment of CD4+ IFN-gamma+ T4p2553-specific cells is observed among cervical
      lymph node cells and intrathyroidal lymphocytes. T4p2553 was equally detectable
      on dendritic cells obtained ex vivo from cervical lymph node cells of NaI-fed or
      control mice, suggesting that the iodide-rich diet contributes to the activation
      of autoreactive cells rather than the generation of the autoantigenic epitope.
      Furthermore, spontaneous T4p2553-specific IgG are not detectable within the
      strong Tg-specific autoantibody response. To our knowledge, these data identify
      for the first time a Tg T cell epitope as a spontaneous target in ISAT.

PMID- 24879794
TI  - Hemin controls T cell polarization in sickle cell alloimmunization.
AB  - Patients with sickle cell disease (SCD) often require transfusions to treat and
      prevent worsening anemia and other SCD complications. However, transfusions can
      trigger alloimmunization against transfused RBCs with serious clinical sequelae.
      Risk factors for alloimmunization in SCD remain poorly understood. We recently
      reported altered regulatory T cell (Treg) and Th responses with higher
      circulating Th1 (IFN-gamma(+)) cytokines in chronically transfused SCD patients
      with alloantibodies as compared with those without alloantibodies. Because
      monocytes play a critical role in polarization of T cell subsets and participate
      in clearance of transfused RBCs, we tested the hypothesis that in response to the
      RBC breakdown product hemin, monocyte control of T cell polarization will differ
      between alloimmunized and non-alloimmunized SCD patients. Exogenous hemin induced
      Treg polarization in purified T cell/monocyte cocultures from healthy volunteers
      through the monocyte anti-inflammatory heme-degrading enzyme heme oxygenase-1.
      Importantly, hemin primarily through its effect on CD16+ monocytes induced an
      anti-inflammatory (higher Treg/lower Th1) polarization state in the non
      alloimmunized SCD group, whereas it had little effect in the alloimmunized group.
      Non-alloimmunized SCD CD16+ monocytes expressed higher basal levels of heme
      oxygenase-1. Furthermore, IL-12, which contributed to a proinflammatory
      polarization state (low Treg/high Th1) in SCD, was dampened in hemin-treated
      stimulated monocytes from non-alloimmunized SCD patients, but not in the
      alloimmunized group. These data suggest that unlike alloimmunized patients, non
      alloimmunized SCD CD16+ monocytes in response to transfused RBC breakdown
      products promote an anti-inflammatory state that is less conducive to
      alloimmunization.

PMID- 24879796
TI  - Targeting PI3K/mTOR overcomes resistance to HER2-targeted therapy independent of
      feedback activation of AKT.
AB  - PURPOSE: Altered PI3K/mTOR signaling is implicated in the pathogenesis of a
      number of breast cancers, including those resistant to hormonal and HER2-targeted
      therapies. EXPERIMENTAL DESIGN: The activity of four classes of PI3K/mTOR
      inhibitory molecules, including a pan-PI3K inhibitor (NVP-BKM120), a p110alpha
      isoform-specific PI3K inhibitor (NVP-BYL719), an mTORC1-specific inhibitor (NVP
      RAD001), and a dual PI3K/mTORC1/2 inhibitor (NVP-BEZ235), was evaluated both in
      vitro and in vivo against a panel of 48 human breast cell lines. RESULTS: Each
      agent showed significant antiproliferative activity in vitro, particularly in
      luminal estrogen receptor-positive and/or HER2(+) cell lines harboring PI3K
      mutations. In addition, monotherapy with each of the four inhibitors led to
      significant inhibition of in vivo growth in HER2(+) breast cancer models. The
      PI3K/mTOR pathway inhibitors were also effective in overcoming both de novo and
      acquired trastuzumab resistance in vitro and in vivo. Furthermore, combined
      targeting of HER2 and PI3K/mTOR leads to increased apoptosis in vitro and
      induction of tumor regression in trastuzumab-resistant xenograft models. Finally,
      as previously shown, targeting mTORC1 alone with RAD001 leads to consistent
      feedback activation of AKT both in vitro and in vivo, whereas the dual mTOR1
      2/PI3K inhibitor BEZ235 eliminates this feedback loop. However, despite these
      important signaling differences, both molecules are equally effective in
      inhibiting tumor cell proliferation both in vitro and in vivo. CONCLUSION: These
      preclinical data support the findings of the BOLERO 3 trial that shows that
      targeting of the PI3K/mTOR pathway in combination with trastuzumab is beneficial
      in trastuzumab-resistant breast cancer.

PMID- 24879798
TI  - Blocking immunosuppressive checkpoints for glioma therapy: the more the Merrier!
AB  - Immunosuppressive checkpoints mediated by IDO, CTLA4, and PD1/PDL1 play a
      critical role in glioma progression and the efficacy of immunotherapies. Combined
      blockade of these immunosuppressive checkpoints in a glioma model elicited long
      term survival. This combined blockade adds to the armamentarium of anti-glioma
      therapies, which could be implemented in clinical trials. Clin Cancer Res;
      20(20); 5147-9. (c)2014 AACR. 

PMID- 24879797
TI  - FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2
      positive metastatic breast cancer.
AB  - On February 22, 2013, the FDA licensed ado-trastuzumab emtansine (Kadcyla;
      Genentech, Inc.) for use as a single agent for the treatment of patients with
      human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer
      (MBC) who previously received trastuzumab and a taxane, separately or in
      combination. The clinical basis for licensure was a phase III trial in 991
      patients with HER2-positive MBC that randomly allocated patients to receive ado
      trastuzumab emtansine (n=495) or lapatinib in combination with capecitabine
      (n=496). The coprimary endpoints were progression-free survival (PFS) based on
      tumor assessments by an independent review committee and overall survival (OS).
      Statistically significant improvements in PFS and OS were observed in patients
      receiving ado-trastuzumab emtansine compared with patients receiving lapatinib
      plus capecitabine [difference in PFS medians of 3.2 months, HR, 0.65 (95%
      confidence interval, CI, 0.55-0.77), P<0.0001 and difference in OS medians of 5.8
      months, HR, 0.68 (95% CI, 0.55-0.85), P=0.0006]. The most common adverse
      reactions in patients receiving ado-trastuzumab emtansine were fatigue, nausea,
      musculoskeletal pain, thrombocytopenia, headache, increased aminotransferase
      levels, and constipation. Other significant adverse reactions included
      hepatobiliary disorders and left ventricular dysfunction. Given the PFS and OS
      results, the benefit-risk profile was considered favorable.

PMID- 24879799
TI  - Real-time monitoring of disease progression in rhesus macaques infected with
      Borrelia turicatae by tick bite.
AB  - The hallmark of disease caused by tick- and louse-borne relapsing fever due to
      Borrelia infection is cyclic febrile episodes, which in humans results in severe
      malaise and may lead to death. To evaluate the pathogenesis of relapsing fever
      due to spirochetes in an animal model closely related to humans, disease caused
      by Borrelia turicatae after tick bite was compared in 2 rhesus macaques in which
      radiotelemetry devices that recorded body temperatures in 24-hour increments were
      implanted. The radiotelemetry devices enabled real-time acquisition of core body
      temperatures and changes in heart rates and electrocardiogram intervals for 28
      consecutive days without the need to constantly manipulate the animals. Blood
      specimens were also collected from all animals for 14 days after tick bite, and
      spirochete densities were assessed by quantitative polymerase chain reaction. The
      complexity of disease caused by relapsing-fever spirochetes was demonstrated in
      the nonhuman primates monitored in real time. The animals experienced prolonged
      episodes of hyperthermia and hypothermia; disruptions in their diurnal patterns
      and repolarization of the heart were also observed. This is the first report of
      the characterizing disease progression with continuous monitoring in an animal
      model of relapsing fever due to Borrelia infection. 

PMID- 24879800
TI  - Geographical distribution and risk association of human papillomavirus genotype
      52-variant lineages.
AB  - Human papillomavirus (HPV) genotype 52 is commonly found in Asian cases of
      cervical cancer but is rare elsewhere. Analysis of 611 isolates collected
      worldwide revealed a remarkable geographical distribution, with lineage B
      predominating in Asia (89.0% vs 0%-5.5%; P(corrected) < .001), whereas lineage A
      predominated in Africa, the Americas, and Europe. We propose that the name "Asian
      lineage" be used to denote lineage B, to signify this feature. Preliminary
      analysis suggested a higher disease risk for lineage B, although
      ethnogeographical confounders could not be excluded. Further studies are
      warranted to verify whether the reported high attribution of disease to HPV52 in
      Asia is due to the high prevalence of lineage B.

PMID- 24879801
TI  - Decreased endothelial nitric oxide bioavailability, impaired microvascular
      function, and increased tissue oxygen consumption in children with falciparum
      malaria.
AB  - Endothelial nitric oxide (NO) bioavailability, microvascular function, and host
      oxygen consumption have not been assessed in pediatric malaria. We measured NO
      dependent endothelial function by using peripheral artery tonometry to determine
      the reactive hyperemia index (RHI), and microvascular function and oxygen
      consumption (VO2) using near infrared resonance spectroscopy in 13 Indonesian
      children with severe falciparum malaria and 15 with moderately severe falciparum
      malaria. Compared with 19 controls, children with severe malaria and those with
      moderately severe malaria had lower RHIs (P = .03); 12% and 8% lower
      microvascular function, respectively (P = .03); and 29% and 25% higher VO2,
      respectively. RHIs correlated with microvascular function in all children with
      malaria (P < .001) and all with severe malaria (P < .001). Children with malaria
      have decreased endothelial and microvascular function and increased oxygen
      consumption, likely contributing to the pathogenesis of the disease. 

PMID- 24879802
TI  - Arachidonic acid downregulates acyl-CoA synthetase 4 expression by promoting its
      ubiquitination and proteasomal degradation.
AB  - ACSL4 is a member of the long-chain acyl-CoA synthetase (ACSL) family with a
      marked preference for arachidonic acid (AA) as its substrate. Although an
      association between elevated levels of ACSL4 and hepatosteatosis has been
      reported, the function of ACSL4 in hepatic FA metabolism and the regulation of
      its functional expression in the liver remain poorly defined. Here we provide
      evidence that AA selectively downregulates ACSL4 protein expression in hepatic
      cells. AA treatment decreased the half-life of ACSL4 protein in HepG2 cells by
      approximately 4-fold (from 17.3 +/- 1.8 h to 4.2 +/- 0.4 h) without causing
      apoptosis. The inhibitory action of AA on ACSL4 protein stability could not be
      prevented by rosiglitazone or inhibitors that interfere with the cellular
      pathways involved in AA metabolism to biologically active compounds. In contrast,
      treatment of cells with inhibitors specific for the proteasomal degradation
      pathway largely prevented the AA-induced ACSL4 degradation. We further show that
      ACSL4 is intrinsically ubiquitinated and that AA treatment can enhance its
      ubiquitination. Collectively, our studies have identified a novel substrate
      induced posttranslational regulatory mechanism by which AA downregulates ACSL4
      protein expression in hepatic cells. 

PMID- 24879803
TI  - Comparative gene identification 58/alpha/beta hydrolase domain 5 lacks
      lysophosphatidic acid acyltransferase activity.
AB  - Mutations in the gene encoding comparative gene identification 58 (CGI
      58)/alpha/beta hydrolase domain 5 (ABHD5) cause Chanarin-Dorfman syndrome,
      characterized by excessive triacylglycerol storage in cells and tissues. CGI-58
      has been identified as a coactivator of adipose TG lipase (ATGL) and a
      lysophosphatidic acid acyltransferase (LPAAT). We developed a molecular model of
      CGI-58 structure and then mutated predicted active site residues and performed
      LPAAT activity assays of recombinant WT and mutated CGI-58. When mutations of
      predicted catalytic residues failed to reduce LPAAT activity, we determined that
      LPAAT activity was due to a bacterial contaminant of affinity purification
      procedures, plsC, the sole LPAAT in Escherichia coli Purification protocols were
      optimized to reduce plsC contamination, in turn reducing LPAAT activity. When CGI
      58 was expressed in SM2-1(DE3) cells that lack plsC, lysates lacked LPAAT
      activity. Additionally, mouse CGI-58 expressed in bacteria as a glutathione-S
      transferase fusion protein and human CGI-58 expressed in yeast lacked LPAAT
      activity. Previously reported lipid binding activity of CGI-58 was revisited
      using protein-lipid overlays. Recombinant CGI-58 failed to bind lysophosphatidic
      acid, but interestingly, bound phosphatidylinositol 3-phosphate [PI(3)P] and
      phosphatidylinositol 5-phosphate [PI(5)P]. Prebinding CGI-58 with PI(3)P or
      PI(5)P did not alter its coactivation of ATGL in vitro. In summary, purified
      recombinant CGI-58 that is functional as an ATGL coactivator lacks LPAAT
      activity. 

PMID- 24879805
TI  - Re: Examining the cost-effectiveness of radiation therapy among older women with
      favorable-risk breast cancer.

PMID- 24879804
TI  - A monophasic extraction strategy for the simultaneous lipidome analysis of polar
      and nonpolar retina lipids.
AB  - Lipid extraction using a monophasic chloroform/methanol/water mixture, coupled
      with functional group selective derivatization and direct infusion nano-ESI-high
      resolution/accurate MS, is shown to facilitate the simultaneous analysis of both
      highly polar and nonpolar lipids from a single retina lipid extract, including
      low abundance highly polar ganglioside lipids, nonpolar sphingolipids, and
      abundant glycerophospholipids. Quantitative comparison showed that the monophasic
      lipid extraction method yielded similar lipid distributions to those obtained
      from established "gold standard" biphasic lipid extraction methods known to
      enrich for either highly polar gangliosides or nonpolar lipids, respectively,
      with only modest relative ion suppression effects. This improved lipid extraction
      and analysis strategy therefore enables detailed lipidome analyses of lipid
      species across a broad range of polarities and abundances, from minimal amounts
      of biological samples and without need for multiple lipid class-specific
      extractions or chromatographic separation prior to analysis. 

PMID- 24879806
TI  - Life expectancy following orbital exenteration.
AB  - Orbital exenteration is a physically debilitating procedure that may be a
      necessity in the management of orbital malignancy. It requires a sensitive
      multidisciplinary approach, both preoperatively and postoperatively. Providing
      life expectancy information for patients during preoperative counselling is
      pertinent to informed consent and in addressing patients' expectations. A
      retrospective review from one tertiary care centre was undertaken for a cohort of
      patients who were exenterated for orbital malignancy between 1998 and 2010. The
      cases were identified using an International Classification of Diseases 10th
      Revision (ICD-10)-derived database and were analysed using Prism statistical
      software (V.5.04). Cause of death was ascertained by liaising with the general
      practitioner and the National Registrar Office for Births, Deaths, and Marriages,
      Southport, UK. In total, 41 men and 32 women were identified. Mean age was 72
      years with 47 cases living and 26 deceased at the time of review. The overall 5
      year survival rate in this study was 64%. Kaplan-Meier analysis for basal cell
      carcinoma (BCC) against non-BCC returned a p value of 0.0199, with an HR of
      0.3927 (CI 0.1788 to 0.8626). Kaplan-Meier analysis for cleared against non
      cleared margins returned a p value of 0.2890, with an HR of 0.6571(CI 0.3024 to
      1.428). Our results represent the highest 5-year survival data to date. However,
      the overall prognosis for patients who undergo orbital exenteration for
      malignancy remains poor. We hypothesise that the causes are multi-factorial. We
      recommend a multidisciplinary approach to the care of these patients, involving
      head and neck teams, oncology and other appropriate specialties, to optimise
      outcomes for this vulnerable patient group. 

PMID- 24879808
TI  - Iris mattress suture: a technique for sectoral iris defect repair.
AB  - Achieving a cosmetic and functional outcome from iris defect repair is a surgical
      challenge. We describe an adaptation of techniques to address a case of 2.5 clock
      hours of sectoral iris tissue defect. Our method combines Siepser's modified
      closed-chamber sliding knot technique with the placement of a double-armed iris
      mattress suture to approximate iris tissue to the scleral wall and thereby create
      a pseudo-iris root. This technique reduces glare and achieves a cosmetic outcome
      for the patient. 

PMID- 24879807
TI  - Results of late surgical intervention in children with early-onset bilateral
      cataracts.
AB  - BACKGROUND: Cataracts are a major cause of childhood blindness globally. Although
      surgically treatable, it is unclear whether children would benefit from such
      interventions beyond the first few years of life, which are believed to
      constitute 'critical' periods for visual development. AIMS: To study visual
      acuity outcomes after late treatment of early-onset cataracts and also to
      determine whether there are longitudinal changes in postoperative acuity.
      METHODS: We identified 53 children with dense cataracts with an onset within the
      first half-year after birth through a survey of over 20,000 rural children in
      India. All had accompanying nystagmus and were older than 8 years of age at the
      time of treatment. They underwent bilateral cataract surgery and intraocular lens
      implantation. We then assessed their best-corrected visual acuity 6 weeks and 6
      months after surgery. RESULTS: 48 children from the pool of 53 showed improvement
      in their visual acuity after surgery. Our longitudinal assessments demonstrated
      further improvements in visual acuity for the majority of these children
      proceeding from the 6-week to 6-month assessment. Interestingly, older children
      in our subject pool did not differ significantly from the younger ones in the
      extent of improvement they exhibit. CONCLUSIONS AND RELEVANCE: Our results
      demonstrate that not only can significant vision be acquired until late in
      childhood, but that neural processes underlying even basic aspects of vision like
      resolution acuity remain malleable until at least adolescence. These data argue
      for the provision of cataract treatment to all children, irrespective of their
      age.

PMID- 24879809
TI  - First clinicial results on the feasibility, quality and reproducibility of
      aberrometry-based intraoperative refraction during cataract surgery.
AB  - OBJECTIVE: To provide the first clinical data in determining the feasibility,
      quality and precision of intraoperative wavefront aberrometry (IWA)-based
      refraction in patients with cataract. DESIGN: IWA refraction was recorded at 7
      defined measurement points during standardised cataract surgery in 74 eyes of 74
      consecutive patients (mean age 69+/-11.3 years). Precision and measurement
      quality was evaluated by the 'limits of agreement' approach, regression analysis,
      correlation analysis, Analysis of variance (ANOVA) and ORs for predicting
      measurement failure. Wavefront map (WFM) quality was objectivised and compared
      with the Pentacam Nuclear Staging analysis. RESULTS: Out of 814 IWA measurement
      attempts, 462 WFMs could be obtained. The most successful readings (n=63) were
      achieved in aphakia with viscoelastic. The highest (50.63%, SD 20.23) and lowest
      (29.19%, SD 13.94) quality of WFMs across all measurement points were found after
      clear corneal incision and in pseudophakia with viscoelastic, respectively. High
      consistency across repeated measures were found for mean spherical equivalent
      (SE) differences in aphakia with -0.01D and pseudophakia with -0.01D, but ranges
      were high (limits of agreement +0.69 D and -0.72 D; +1.53 D and -1.54 D,
      respectively). With increasing WFM quality, higher precision in measurements was
      observed. CONCLUSIONS: This is the first report addressing quality and
      reproducibility of WA in a large sample. IWA refraction in aphakia, for instance,
      appears to be reliable once stable and pressurised anterior chamber conditions
      are achieved. More efforts are required to improve the precision and quality of
      measurements before IWA can be used to guide the surgical refractive plan in
      cataract surgery.

PMID- 24879810
TI  - DMEK lenticule preparation from donor corneas using a novel 'SubHyS' technique
      followed by anterior corneal dissection.
AB  - PURPOSE: To describe a novel submerged hydro-separation (SubHyS) technique
      followed by anterior corneal dissection to prepare a Descemet endothelial graft
      (DEG) for Descemet's membrane endothelial keratoplasty from human donor corneas.
      METHODS: 30 human donor corneas were immersed in liquid (organ culture (OC)
      storage medium). Using a 25-gauge needle, approximately 0.3 mL of OC was injected
      (SubHyS) in the posterior stroma to create a liquid bubble. The bubbled cornea
      was mounted onto a modified artificial chamber with the epithelial side facing
      the air. The endothelium was protected with a viscoelastic solution. The anterior
      cornea was excised with a Barron radial vacuum trephine and the residual
      peripheral stroma was removed manually using micro-scissors. The DEG was
      dismounted and washed. The endothelial cell density (ECD) and mortality of the
      prepared DEG was determined. All the DEGs were preserved in deturgescent medium
      for 7 days using a cornea claw which was fixed to the sclera. ECD and mortality
      were checked post preservation. RESULTS: Complete detachment of Descemet's
      membrane and stroma was achieved in all 30 cases. Bubble burst was observed in
      five cases (excluded from the study) due to overfilling of the liquid. The
      average diameter of the excised DEG was 10.96 mm. The average endothelial cell
      loss post preservation was 27.69%. Histological analysis confirmed elimination of
      the residual stroma (n=13). CONCLUSIONS: The DEGs can be preserved in a
      deturgescent medium for up to 7 days. The procedure provides a standardised, pre
      validated (quality assured), pre-separated, no-touch, ready-to-use tissue and
      also reduces the preparation time. Further, the tissues can be trephined as per
      the surgeon's convenience and can either be rolled or a contact lens could be
      used for final delivery of the DEG using a surgical glide.

PMID- 24879811
TI  - Treatment of diffuse subretinal fibrosis uveitis with rituximab.
AB  - Diffuse subretinal fibrosis uveitis (DUS) syndrome is a rare form of
      granulomatous multifocal choroiditis (MFC) characterised by enlarging areas of
      subretinal fibrosis (SRF) which coalesce with subsequent macular involvement and
      visual loss. First described by Palestine, DUS carries a poor visual prognosis
      despite use of high-dose corticosteroids and systemic immunosuppression. We
      report two cases of bilateral DUS successfully treated with rituximab. We believe
      given the B-cell predominance in the underlying pathogenesis of the disease,
      rituximab should be considered first line in the management of this potentially
      devastating disease. 

PMID- 24879812
TI  - Comparison of surgical outcomes between simple posterior layer advancement of
      lower eyelid retractors and combination with a lateral tarsal strip procedure for
      involutional entropion in a Japanese population.
AB  - AIMS: To compare the effectiveness of simple posterior layer advancement of the
      lower eyelid retractor (LER) and combination surgery of posterior layer
      advancement of the LER with a lateral tarsal strip procedure for involutional
      lower eyelid entropion in a Japanese population. METHODS: 46 eyelids of 37
      patients with horizontal laxity (Group A) and 47 eyelids of 42 patients without
      horizontal laxity (Group B) that underwent simple posterior layer advancement of
      the LER, and 47 eyelids of 37 patients with horizontal laxity that had the
      combination surgery (Group C) were retrospectively reviewed. RESULTS: All eyelids
      were judged as successfully corrected without recurrence in Groups B and C. On
      the other hand, although 42 eyelids (91.3%) were successfully altered in Group A,
      four eyelids (8.7%) showed recurrence at a mean period of 7.6 months
      postoperatively. Surgical success rates in Groups B and C tended to be higher
      than in Group A (p=0.056). CONCLUSIONS: The combination surgery in Group C and
      simple posterior layer advancement of the LER in Group B provided complete
      surgical success. The present study suggests the importance of preoperative
      evaluation of horizontal laxity, allowing surgeons to perform the least amount of
      surgery to achieve success.

PMID- 24879815
TI  - Poorest socioeconomic groups still have highest rates of cancer.

PMID- 24879813
TI  - D-dimer to guide the duration of anticoagulation in patients with venous
      thromboembolism: a management study.
AB  - The optimal duration of anticoagulation in patients with venous thromboembolism
      (VTE) is uncertain. We investigated whether persistently negative D-dimers in
      patients with vein recanalization or stable thrombotic burden can identify
      subjects at low recurrence risk. Outpatients with a first VTE (unprovoked or
      associated with weak risk factors) were eligible after at least 3 months (12 in
      those with residual thrombosis) of anticoagulation. They received serial D-dimer
      measurements using commercial assays with predefined age/sex-specific cutoffs and
      were followed for up to 2 years. Of 1010 patients, anticoagulation was stopped in
      528 (52.3%) with persistently negative D-dimer who subsequently experienced 25
      recurrences (3.0% pt-y; 95% confidence interval [CI], 2.0-4.4%). Of the remaining
      482 patients, 373 resumed anticoagulation and 109 refused it. Recurrent VTE
      developed in 15 patients (8.8% pt-y; 95% CI, 5.0-14.1) of the latter group and in
      4 of the former (0.7% pt-y; 95% CI, 0.2-1.7; hazard ratio = 2.92; 95% CI, 1.87
      9.72; P = .0006). Major bleeding occurred in 14 patients (2.3% pt-y; 95% CI, 1.3
      3.9) who resumed anticoagulation. Serial D-dimer measurement is suitable in
      clinical practice for the identification of VTE patients in whom anticoagulation
      can be safely discontinued. This study was registered at clinicaltrials.gov as
      #NCT00954395. 

PMID- 24879814
TI  - In utero depletion of fetal hematopoietic stem cells improves engraftment after
      neonatal transplantation in mice.
AB  - Although in utero hematopoietic cell transplantation is a promising strategy to
      treat congenital hematopoietic disorders, levels of engraftment have not been
      therapeutic for diseases in which donor cells have no survival advantage. We used
      an antibody against the murine c-Kit receptor (ACK2) to deplete fetal host
      hematopoietic stem cells (HSCs) and increase space within the hematopoietic niche
      for donor cell engraftment. Fetal mice were injected with ACK2 on embryonic days
      13.5 to 14.5 and surviving pups were transplanted with congenic hematopoietic
      cells on day of life 1. Low-dose ACK2 treatment effectively depleted HSCs within
      the bone marrow with minimal toxicity and the antibody was cleared from the serum
      before the neonatal transplantation. Chimerism levels were significantly higher
      in treated pups than in controls; both myeloid and lymphoid cell chimerism
      increased because of higher engraftment of HSCs in the bone marrow. To test the
      strategy of repeated HSC depletion and transplantation, some mice were treated
      with ACK2 postnatally, but the increase in engraftment was lower than that seen
      with prenatal treatment. We demonstrate a successful fetal conditioning strategy
      associated with minimal toxicity. Such strategies could be used to achieve
      clinically relevant levels of engraftment to treat congenital stem cell
      disorders.

PMID- 24879816
TI  - Is animal research sufficiently evidence based to be a cornerstone of biomedical
      research?

PMID- 24879817
TI  - Understanding statistical hypothesis testing.

PMID- 24879818
TI  - US investigation confirms Veterans Affairs staff kept multiple waiting lists.

PMID- 24879820
TI  - Going hungry in America.

PMID- 24879821
TI  - Small hospitals could help to bolster community services, says NHS chief.

PMID- 24879823
TI  - Molecular pathways: the immunogenic effects of platinum-based chemotherapeutics.
AB  - The platinum-based drugs cisplatin, carboplatin, and oxaliplatin belong to the
      most widely used chemotherapeutics in oncology, showing clinical efficacy against
      many solid tumors. Their main mechanism of action is believed to be the induction
      of cancer cell apoptosis as a response to their covalent binding to DNA. In
      recent years, this picture has increased in complexity, based on studies
      indicating that cellular molecules other than DNA may potentially act as targets,
      and that part of the antitumor effects of platinum drugs occurs through
      modulation of the immune system. These immunogenic effects include modulation of
      STAT signaling; induction of an immunogenic type of cancer cell death through
      exposure of calreticulin and release of ATP and high-mobility group protein box-1
      (HMGB-1); and enhancement of the effector immune response through modulation of
      programmed death receptor 1-ligand and mannose-6-phosphate receptor expression.
      Both basic and clinical studies indicate that at least part of the antitumor
      efficacy of platinum chemotherapeutics may be due to immune potentiating
      mechanisms. Clinical studies exploiting this novel mechanism of action of these
      old cancer drugs have been initiated. Here, we review the literature on the
      immunogenic effects of platinum, summarize the clinical advances using platinum
      as a cytotoxic compound with immune adjuvant properties, and discuss the
      limitations to these studies and the gaps in our understanding of the immunologic
      effects of these drugs. Clin Cancer Res; 20(11); 2831-7. (c)2014 AACR. 

PMID- 24879825
TI  - Prevention of head louse infestation: a randomised, double-blind, cross-over
      study of a novel concept product, 1% 1,2-octanediol spray versus placebo.
AB  - OBJECTIVES: To determine whether regular use of a spray containing 1,2-octanediol
      1%, which has been shown to inhibit survival of head lice, is able to work as a
      preventive against establishment of new infestations. SETTING: Randomised, double
      blind, cross-over, community study in Cambridgeshire, UK. PARTICIPANTS: 63 male
      and female schoolchildren aged 4-16 years judged to have a high risk of recurrent
      infestation. Only the youngest member of a household attending school
      participated. INTERVENTIONS: Participants were treated to eliminate lice,
      randomised between 1% octanediol or placebo sprays for 6 weeks then crossed-over
      to the other spray for 6 weeks. Parents applied the sprays at least twice weekly
      or more frequently if the hair was washed. Investigators monitored weekly for
      infestation and replenished supplies of spray. PRIMARY AND SECONDARY OUTCOME
      MEASURES: The primary endpoint was the time taken until the first infestation
      event occurred. The secondary measure was safety of the product in regular use.
      RESULTS: Intention-to-treat analysis found a total of 32 confirmed infestations
      in 20 participants, with 9 of them infested while using both products. In these
      nine participants the time to first infestation showed a significant advantage to
      1% octanediol (p=0.0129). Per-protocol analysis showed only trends because the
      population included was not large enough to demonstrate significance. There were
      no serious adverse events and only two adverse events possibly related to
      treatment, one was a case of transient erythema and another of a rash that
      resolved after 5 days. CONCLUSIONS: Routine use of 1% octanediol spray provided a
      significant level of protection from infestation. It was concluded that this
      product is effective if applied regularly and thoroughly. TRIAL REGISTRATION
      NUMBER: ISRCTN09524995.

PMID- 24879819
TI  - Time to treatment with recombinant tissue plasminogen activator and outcome of
      stroke in clinical practice: retrospective analysis of hospital quality assurance
      data with comparison with results from randomised clinical trials.
AB  - OBJECTIVE: To study the time dependent effectiveness of thrombolytic therapy for
      acute ischaemic stroke in daily clinical practice. DESIGN: A retrospective cohort
      study using data from a large scale, comprehensive population based state-wide
      stroke registry in Germany. SETTING: All 148 hospitals involved in acute stroke
      care in a large state in southwest Germany with 10.4 million inhabitants.
      PARTICIPANTS: Data from 84,439 patients with acute ischaemic stroke were
      analysed, 10,263 (12%) were treated with thrombolytic therapy and 74,176 (88%)
      were not treated. MAIN OUTCOME MEASURES: Primary endpoint was the dichotomised
      score on a modified Rankin scale at discharge ("favourable outcome" score 0 or 1
      or "unfavourable outcome" score 2-6) analysed by binary logistic regression.
      Patients treated with recombinant tissue plasminogen activator (rtPA) were
      categorised according to time from onset of stroke to treatment. Analogous
      analyses were conducted for the association between rtPA treatment of stroke and
      in-hospital mortality. As a co-primary endpoint the chance of a lower modified
      Rankin scale score at discharge was analysed by ordinal logistic regression
      analysis (shift analysis). RESULTS: After adjustment for characteristics of
      patients, hospitals, and treatment, rtPA was associated with better outcome in a
      time dependent pattern. The number needed to treat ranged from 4.5 (within first
      1.5 hours after onset; odds ratio 2.49) to 18.0 (up to 4.5 hours; odds ratio
      1.26), while mortality did not vary up to 4.5 hours. Patients treated with rtPA
      beyond 4.5 hours (including mismatch based approaches) showed a significantly
      better outcome only in dichotomised analysis (odds ratio 1.25, 95% confidence
      interval 1.01 to 1.55) but the mortality risk was higher (1.45, 1.08 to 1.92).
      CONCLUSION: The effectiveness of thrombolytic therapy in daily clinical practice
      might be comparable with the effectiveness shown in randomised clinical trials
      and pooled analysis. Early treatment was associated with favourable outcome in
      daily clinical practice, which underlines the importance of speeding up the
      process for thrombolytic therapy in hospital and before admission to achieve
      shorter time from door to needle and from onset to treatment for thrombolytic
      therapy.

PMID- 24879826
TI  - Patient evaluation of hospital outcomes: an analysis of open-ended comments from
      extreme clusters in a national survey.
AB  - OBJECTIVES: A recent study identified patients in six distinct response groups
      based on their evaluations of outcomes related to overall satisfaction,
      malpractice and benefit of treatment. This study validates the response clusters
      by analysing and comparing open-ended comments from the extreme positive and
      extreme negative response groups. DESIGN: Qualitative content analysis. SETTING:
      Data from open-ended comment fields provided by patients who completed a national
      patient-experience survey carried out in Norway in 2011. 10 514 patients
      responded to the questionnaire and 3233 provided comments. A random sample of 50
      open-ended comments from respondents representing cluster 1 ('excellent
      services'), cluster 5 ('services have clear improvement needs') and outliers
      ('very poor services') was reviewed. RESULTS: 3 distinct patient profiles were
      identified. More than half of the comments in cluster 1 included descriptions of
      positive healthcare experiences, one addressed patient safety issues. Only 1 of
      the comments in cluster 5 was positive, and 12 were related to safety. All
      comments from the outliers were negative, and more than three-quarters reported
      experiences related to malpractice or adverse events. Recurring themes did not
      differ significantly between the three respondent groups, but significant
      differences were found for the descriptions and severity of the experiences.
      CONCLUSIONS: Patients in negative response groups had distinct and much poorer
      healthcare descriptions than those in the extreme positive group, supporting the
      interpretation of quality differences between these groups. Further research
      should assess ways of combining statistical cluster information and qualitative
      comments, which could be used for local quality improvement and public reporting.

PMID- 24879827
TI  - Comparison of the ultra-low-dose Veo algorithm with the gold standard filtered
      back projection for detecting pulmonary asbestos-related conditions: a clinical
      observational study.
AB  - OBJECTIVES: Radiation delivered during CT is a major concern, especially for
      individuals undergoing repeated screening. We aimed to compare a new ultra-low
      dose algorithm called Veo with the gold standard filtered back projection (FBP)
      for detecting pulmonary asbestos-related conditions. SETTING: University Hospital
      CHU G. Montpied, Clermont-Ferrand, France PARTICIPANTS: Asbestos-exposed workers
      were recruited following referral to screening for asbestos-related conditions.
      Two acquisitions were performed on a 64-slice CT: the gold standard FBP followed
      by Veo reconstruction. OUTCOME MEASURES: Two radiologists independently assessed
      asbestos-related abnormalities, pulmonary nodules, radiation doses and image
      quality (noise). RESULTS: We included 27 asbestos-exposed workers (63.3+/-6.5
      years with 11.9+/-9.7 years of asbestos exposure). We observed 297 pleural
      plaques in 20 participants (74%). All patients (100%) had pulmonary nodules,
      totalling 167 nodules. Detection rates did not differ for pleural plaques (Veo
      87% vs FBP 97%, NS), pleural thickening (100% for both) and pulmonary nodules
      (80% for both). Interstitial abnormalities were depicted less frequently with Veo
      than FBP. False negative and false positive did not exceed 2.7%. Compared with
      FBP, Veo decreased the radiation dose up to 87% (Veo 0.23+/-0.07 vs FBP 1.83+/
      0.88 mSv, p<0.001). The objective image noise also decreased with Veo as much as
      23% and signal-to-noise ratio increased up to 33%. CONCLUSIONS: A low-dose CT
      with Veo reconstruction substantially reduced radiation. Veo compared favourably
      with FBP in detecting pleural plaques, pleural thickening and pulmonary nodules.
      These results should be confirmed on a larger sample size before the use of Veo
      in clinical routine practice in asbestos-related conditions, especially regarding
      the low prevalence of interstitial abnormalities in this study. TRIAL
      REGISTRATION NUMBER: NCT01955018.

PMID- 24879828
TI  - An overview and methodological assessment of systematic reviews and meta-analyses
      of enhanced recovery programmes in colorectal surgery.
AB  - OBJECTIVES: To identify and critically assess the extent to which systematic
      reviews of enhanced recovery programmes for patients undergoing colorectal
      surgery differ in their methodology and reported estimates of effect. DESIGN:
      Review of published systematic reviews. We searched the Cochrane Database of
      Systematic Reviews, the Database of Abstracts of Reviews of Effects (DARE) and
      Health Technology Assessment (HTA) Database from 1990 to March 2013. Systematic
      reviews of enhanced recovery programmes for patients undergoing colorectal
      surgery were eligible for inclusion. PRIMARY AND SECONDARY OUTCOME MEASURES: The
      primary outcome was length of hospital stay. We assessed changes in pooled
      estimates of treatment effect over time and how these might have been influenced
      by decisions taken by researchers as well as by the availability of new trials.
      The quality of systematic reviews was assessed using the Centre for Reviews and
      Dissemination (CRD) DARE critical appraisal process. RESULTS: 10 systematic
      reviews were included. Systematic reviews of randomised controlled trials have
      consistently shown a reduction in length of hospital stay with enhanced recovery
      compared with traditional care. The estimated effect tended to increase from 2006
      to 2010 as more trials were published but has not altered significantly in the
      most recent review, despite the inclusion of several unique trials. The best
      estimate appears to be an average reduction of around 2.5 days in primary
      postoperative length of stay. Differences between reviews reflected differences
      in interpretation of inclusion criteria, searching and analytical methods or
      software. CONCLUSIONS: Systematic reviews of enhanced recovery programmes show a
      high level of research waste, with multiple reviews covering identical or very
      similar groups of trials. Where multiple reviews exist on a topic, interpretation
      may require careful attention to apparently minor differences between reviews.
      Researchers can help readers by acknowledging existing reviews and through clear
      reporting of key decisions, especially on inclusion/exclusion and on statistical
      pooling.

PMID- 24879829
TI  - Identifying hopelessness in population research: a validation study of two brief
      measures of hopelessness.
AB  - OBJECTIVE: Hopelessness is an important construct in psychosocial epidemiology,
      but there is great pressure on the length of questionnaire measures in large
      scale population and clinical studies. We examined the validity and test-retest
      reliability of two brief measures of hopelessness, an existing negatively worded
      two-item measure of hopelessness (Brief-H-Neg) and a positively worded version of
      the same instrument (Brief-H-Pos). DESIGN: Cohort study. SETTING: Control arm of
      the UK Collaborative Trial of Ovarian Cancer Screening. PARTICIPANTS: A non
      clinical research-based sample of 5000 postmenopausal women selected from 56 512
      participants. PRIMARY AND SECONDARY OUTCOME MEASURES: Spearman's rank correlation
      of brief measures of hopelessness with the Beck Hopelessness Scale (BHS).
      Spearman's rank correlation with the Centre for Epidemiological Studies
      Depression Scale (CES-D) and change in mean score on repeat testing. METHODS: Two
      short hopelessness measures, a negatively worded brief measure of hopelessness
      (Brief-H-Neg) and a positively worded brief measure of hopelessness (Brief-H
      Pos), were administered by postal questionnaire to 5000 women together with the
      20-item BHS and 20-item CES-D. The Brief-H-Neg and Brief-H-Pos were
      readministered to 500 women after a 2-week interval. RESULTS: 2413 postmenopausal
      women (mean age 68.9 years) completed the questionnaire. The Brief-H-Neg and
      Brief-H-Pos correlated 0.93 and 0.87 with the BHS after correction for
      attenuation and their association with the CES-D mirrored that seen with the BHS
      (Spearman's rank correlation 0.88 and 0.68, respectively). There was no change in
      mean scores on the two measures with repeat testing in the 433 women who
      completed them and test-retest reliability was good (intraclass correlations
      Brief-H-Neg 0.67 and Brief-H-Pos 0.72). CONCLUSIONS: These findings provide
      support for the validity of the Brief-H-Neg and Brief-H-Pos. These brief measures
      are likely to be useful in large population studies assessing hopelessness. TRIAL
      REGISTRATION NUMBER: NCT00058032.

PMID- 24879830
TI  - Improving skills and care standards in the support workforce for older people: a
      realist review.
AB  - INTRODUCTION: In the context of a population that is growing older, and a number
      of high-profile scandals about care standards in hospital and community settings,
      having a skilled and knowledgeable workforce caring for older people is an
      ethical and policy imperative. Support workers make up the majority of the
      workforce in health and social care services for older people (aged 65 years and
      over), and yet little is known about the best way to facilitate their
      development. Given this gap, this review will draw on evidence to address the
      question: how can workforce development interventions improve the skills and the
      care standards of support workers within older people's health and social care
      services? METHODS AND ANALYSIS: As we are interested in how and why workforce
      development interventions might work, in what circumstances and with whom, we
      will conduct a realist review, sourcing evidence from health, social care,
      policing and education. The review will be conducted in four steps over 18 months
      to (1) construct a theoretical framework, that is, the review's programme
      theories; (2) retrieve, review and synthesise evidence relating to interventions
      designed to develop the support workforce guided by the programme theories; (3)
      'test out' our synthesis findings and refine the programme theories, establish
      their practical relevance/potential for implementation and (4) formulate
      recommendations about improvements to current workforce development interventions
      to contribute to the improvement of care standards in older people's health and
      social care services, potentially transferrable to other services. ETHICS AND
      DISSEMINATION: Ethical approval is not required to undertake this review.
      Knowledge exchange activities through stakeholder engagement and online postings
      are embedded throughout the lifetime of the project. The main output from this
      review will be a new theory driven framework for skill development for the
      support workforce in health and social care for older people. TRIAL REGISTRATION
      NUMBER: CRD42013006283.

PMID- 24879831
TI  - Cancer prevention through stealth: science, policy advocacy, and multilevel
      governance in the establishment of a "National Tobacco Control Regime" in the
      United States.
AB  - The role of the US federal government in developing tobacco control through a
      cooperative, interactive program with state and local private and public
      organizations has been underestimated. This article investigates how the
      government initiated and sustained a program of "capacity building" through the
      scientific authority of the National Cancer Institute, beginning in the 1980s.
      There are several major questions to be answered: (1) How did this program manage
      to be adopted and sustained despite the well-documented hindrances to effective
      tobacco control policy at the federal level? (2) How did a tobacco control policy
      program become incorporated into the scientific research agenda of the National
      Cancer Institute? (3) How have science, social factors, and government at various
      levels interacted in this capacity-building program? The study emphasizes how the
      US federal government, blocked by a tobacco-friendly Congress from enacting
      effective tobacco control legislation, utilized its scientific research role and,
      with the cooperation of other levels of government and large, private antitobacco
      organizations, established an ongoing policy effort. 

PMID- 24879832
TI  - Clinical neurology: why this still matters in the 21st century.
AB  - This review argues that even with the tremendous advances in diagnostic
      neuroimaging that the clinical skills involved in clinical neurology (ie,
      history, examination, localisation and differential diagnosis) remain key. Yet a
      number of recent audits suggest that large numbers of patients are failing to be
      assessed properly with a risk of patient harm, costly, unnecessary or
      inappropriate investigations, or delayed diagnosis. We review some of the reasons
      why patients are not being assessed properly neurologically, in part as many
      doctors have limited neurological exposure and are hence neurophobic. We propose
      that a solution to these issues centres around ensuring that a core set of basic
      neurological skills is taught at an undergraduate level, whereas higher level
      skills, such as the use of heuristics, are taught at postgraduate level. 

PMID- 24879833
TI  - Exendin-4, a GLP-1 receptor agonist, attenuates prostate cancer growth.
AB  - Recently, pleiotropic benefits of incretin therapy beyond glycemic control have
      been reported. Although cancer is one of the main causes of death in diabetic
      patients, few reports describe the anticancer effects of incretin. Here, we
      examined the effect of the incretin drug exendin (Ex)-4, a GLP-1 receptor (GLP
      1R) agonist, on prostate cancer. In human prostate cancer tissue obtained from
      patients after they had undergone radical prostatectomy, GLP-1R expression
      colocalized with P504S, a marker of prostate cancer. In in vitro experiments, Ex
      4 significantly decreased the proliferation of the prostate cancer cell lines
      LNCap, PC3, and DU145, but not that of ALVA-41. This antiproliferative effect
      depended on GLP-1R expression. In accordance with the abundant expression of GLP
      1R in LNCap cells, a GLP-1R antagonist or GLP-1R knockdown with small interfering
      RNA abolished the inhibitory effect of Ex-4 on cell proliferation. Although Ex-4
      had no effect on either androgen receptor activation or apoptosis, it decreased
      extracellular signal-regulated kinase (ERK)-mitogen-activated protein kinase
      (MAPK) phosphorylation in LNCap cells. Importantly, Ex-4 attenuated in vivo
      prostate cancer growth induced by transplantation of LNCap cells into athymic
      mice and significantly reduced the tumor expression of P504S, Ki67, and
      phosphorylated ERK-MAPK. These data suggest that Ex-4 attenuates prostate cancer
      growth through the inhibition of ERK-MAPK activation. 

PMID- 24879834
TI  - The adaptor protein APPL2 inhibits insulin-stimulated glucose uptake by
      interacting with TBC1D1 in skeletal muscle.
AB  - Insulin stimulates glucose uptake by promoting the trafficking of GLUT4 to the
      plasma membrane in muscle cells, and impairment of this insulin action
      contributes to hyperglycemia in type 2 diabetes. The adaptor protein APPL1
      potentiates insulin-stimulated Akt activation and downstream actions. However,
      the physiological functions of APPL2, a close homolog of APPL1, in regulating
      glucose metabolism remain elusive. We show that insulin-evoked plasma membrane
      recruitment of GLUT4 and glucose uptake are impaired by APPL2 overexpression but
      enhanced by APPL2 knockdown. Likewise, conditional deletion of APPL2 in skeletal
      muscles enhances insulin sensitivity, leading to an improvement in glucose
      tolerance. We identified the Rab-GTPase-activating protein TBC1D1 as an
      interacting partner of APPL2. Insulin stimulates TBC1D1 phosphorylation on serine
      235, leading to enhanced interaction with the BAR domain of APPL2, which in turn
      suppresses insulin-evoked TBC1D1 phosphorylation on threonine 596 in cultured
      myotubes and skeletal muscle. Substitution of serine 235 with alanine diminishes
      APPL2-mediated inhibition on insulin-dependent TBC1D1 phosphorylation on
      threonine 596 and the suppressive effects of TBC1D1 on insulin-induced glucose
      uptake and GLUT4 translocation to the plasma membrane in cultured myotubes.
      Therefore, the APPL2-TBC1D1 interaction is a key step to fine tune insulin
      stimulated glucose uptake by regulating the membrane recruitment of GLUT4 in
      skeletal muscle. 

PMID- 24879835
TI  - Incidence of lactic acidosis in patients with type 2 diabetes with and without
      renal impairment treated with metformin: a retrospective cohort study.
AB  - OBJECTIVE: To determine whether the use of metformin in type 2 diabetic patients
      with various kidney functions is associated with an increased risk of lactic
      acidosis (LA). RESEARCH DESIGN AND METHODS: This study was a retrospective
      analysis of U.K. patient records from the Clinical Practice Research Datalink
      database from 1 January 2007 to 31 December 2012. Inclusion criteria were 1)
      diagnosis of type 2 diabetes before 1 January 2007, 2) treatment with metformin,
      and 3) at least one assessment of renal function between 2007 and 2012. Renal
      function was assessed by glomerular filtration rate and categorized as normal
      (N), mildly reduced (Mi), moderately reduced (Mo), or severely reduced (Se)
      function. The outcome of the study was LA. RESULTS: A total of 77,601 patients
      treated with metformin for type 2 diabetes were identified. There were 35 LA
      events (10.37 [95% CI 7.22-14.42] per 100,000 patient-years) of which none were
      fatal and 23 were linked to a comorbidity. No significant difference in the
      incidence of LA was observed across N, Mi, Mo and Se renal function groups (7.6
      [0.9-27.5], 4.6 [2.00-9.15], 17 [10.89-25.79], and 39 [4.72-140.89] cases per
      100,000 patient-years, respectively). CONCLUSIONS: The overall LA incidence rate
      for patients on metformin in this study was within the range of rates reported in
      the literature for patients with type 2 diabetes, and no significant difference
      was observed among patients with N, Mi, Mo, and Se function.

PMID- 24879837
TI  - Added value of soluble tumor necrosis factor-alpha receptor 1 as a biomarker of
      ESRD risk in patients with type 1 diabetes.
AB  - OBJECTIVE: Recent studies have suggested that circulating levels of the tumor
      necrosis factor-alpha receptor 1 (sTNFalphaR1) may be a useful predictor for the
      risk of end-stage renal disease (ESRD) in patients with diabetes. However, its
      potential utility as a biomarker has not been formally quantified. RESEARCH
      DESIGN AND METHODS: Circulating levels of sTNFalphaR1 were assessed in 429
      patients with type 1 diabetes and overt nephropathy from the Finnish Diabetic
      Nephropathy (FinnDiane) cohort study. Predictors of incident ESRD over a median
      of 9.4 years of follow-up were determined by Cox regression and Fine-Gray
      competing risk analyses. The added value of sTNFalphaR1 was estimated via time
      dependent receiver operating characteristic curves, net reclassification index
      (NRI), and integrated discrimination improvement (IDI) for survival data.
      RESULTS: A total of 130 individuals developed ESRD (28%; ESRD incidence rate of
      3.4% per year). In cause-specific modeling, after adjusting for baseline renal
      status, predictors of increased incidence of ESRD in patients with overt
      nephropathy were an elevated HbA1c, shorter duration of diabetes, and circulating
      levels of sTNFalphaR1. Notably, sTNFalphaR1 outperformed estimated glomerular
      filtration rate in terms of R(2). Circulating levels of the sTNFalphaR1 also
      remained associated with ESRD after adjusting for the competing risk of death. A
      prediction model including sTNFalphaR1 (as a -0.5 fractional polynomial) was
      superior to a model without it, as demonstrated by better global fit, an
      increment of R(2), the C index, and area under the curve. Estimates of IDI and
      NRI(>0) were 0.22 (95% CI 0.16-0.28; P < 0.0001) and 0.98 (0.78-1.23; P <
      0.0001), respectively. The median increment in the risk score after including
      sTNFalphaR1 in the prediction model was 0.18 (0.12-0.30; P < 0.0001).
      CONCLUSIONS: Circulating levels of sTNFalphaR1 are independently associated with
      the cumulative incidence of ESRD. This association is both significant and
      biologically plausible and appears to provide added value as a biomarker, based
      on the absolute values of NRI and IDI.

PMID- 24879836
TI  - Efficacy and safety of dulaglutide added onto pioglitazone and metformin versus
      exenatide in type 2 diabetes in a randomized controlled trial (AWARD-1).
AB  - OBJECTIVE: To compare the efficacy and safety of dulaglutide, a once-weekly GLP-1
      receptor agonist, with placebo and exenatide in type 2 diabetic patients. The
      primary objective was to determine superiority of dulaglutide 1.5 mg versus
      placebo in HbA1c change at 26 weeks. RESEARCH DESIGN AND METHODS: This 52-week,
      multicenter, parallel-arm study (primary end point: 26 weeks) randomized patients
      (2:2:2:1) to dulaglutide 1.5 mg, dulaglutide 0.75 mg, exenatide 10 MUg, or
      placebo (placebo-controlled period: 26 weeks). Patients were treated with
      metformin (1,500-3,000 mg) and pioglitazone (30-45 mg). Mean baseline HbA1c was
      8.1% (65 mmol/mol). RESULTS: Least squares mean +/- SE HbA1c change from baseline
      to the primary end point was -1.51 +/- 0.06% (-16.5 +/- 0.7 mmol/mol) for
      dulaglutide 1.5 mg, -1.30 +/- 0.06% (-14.2 +/- 0.7 mmol/mol) for dulaglutide 0.75
      mg, -0.99 +/- 0.06% (-10.8 +/- 0.7 mmol/mol) for exenatide, and -0.46 +/- 0.08% (
      5.0 +/- 0.9 mmol/mol) for placebo. Both dulaglutide doses were superior to
      placebo at 26 weeks (both adjusted one-sided P < 0.001) and exenatide at 26 and
      52 weeks (both adjusted one-sided P < 0.001). Greater percentages of patients
      reached HbA1c targets with dulaglutide 1.5 mg and 0.75 mg than with placebo and
      exenatide (all P < 0.001). At 26 and 52 weeks, total hypoglycemia incidence was
      lower in patients receiving dulaglutide 1.5 mg than in those receiving exenatide;
      no dulaglutide-treated patients reported severe hypoglycemia. The most common
      gastrointestinal adverse events for dulaglutide were nausea, vomiting, and
      diarrhea. Events were mostly mild to moderate and transient. CONCLUSIONS: Both
      once-weekly dulaglutide doses demonstrated superior glycemic control versus
      placebo and exenatide with an acceptable tolerability and safety profile.

PMID- 24879838
TI  - Metabolic syndrome, C-reactive protein, and mortality in U.S. Blacks and Whites:
      the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study.
AB  - OBJECTIVE: We evaluate associations of metabolic syndrome (MetS), C-reactive
      protein (CRP), and a CRP-incorporated definition of MetS (CRPMetS) with risk of
      all-cause mortality in a biracial population. RESEARCH DESIGN AND METHODS: We
      studied 23,998 participants in the Reasons for Geographic and Racial Differences
      in Stroke (REGARDS) cohort, an observational study of black and white adults >=45
      years old across the U.S. Elevated CRP was defined as >=3 mg/L and MetS by the
      revised Third Report of the Expert Panel on Detection, Evaluation, and Treatment
      of High Blood Cholesterol in Adults (Adult Treatment Panel III; ATP III) criteria
      (three of five components). CRPMetS was defined as presence of three out of six
      components, with elevated CRP added to ATP III criteria as a sixth component. Cox
      models were used to calculate hazard ratios (HRs) for all-cause mortality, and
      population attributable risk (PAR) was calculated. Stratified analyses based on
      race and diabetes status were performed. RESULTS: There were 9,741 participants
      (41%) with MetS and 12,179 (51%) with CRPMetS at baseline. Over 4.8 years of
      follow-up, 2,050 participants died. After adjustment for multiple confounders,
      MetS, elevated CRP, and CRPMetS were each significantly associated with increased
      mortality risk (HRs 1.26 [95% CI 1.15-1.38], 1.55 [1.41-1.70], and 1.34 [1.22
      1.48], respectively). The PAR was 9.5% for MetS, 18.1% for CRP, and 14.7% for
      CRPMetS. Associations of elevated CRP and of CRPMetS with mortality were
      significantly greater in whites than blacks, while no differences in associations
      were observed based on diabetes status. CONCLUSIONS: By definition, CRPMetS
      identifies more people at risk than MetS but still maintains a similar mortality
      risk. Incorporating CRP into the definition for MetS may be useful in identifying
      additional high-risk populations to target for prevention.

PMID- 24879839
TI  - Glucose control and medication adherence among veterans with diabetes and serious
      mental illness: does collocation of primary care and mental health care matter?
AB  - OBJECTIVE: Persons with serious mental illness (SMI) may benefit from collocation
      of medical and mental health healthcare professionals and services in attending
      to their chronic comorbid medical conditions. We evaluated and compared glucose
      control and diabetes medication adherence among patients with SMI who received
      collocated care to those not receiving collocated care (which we call usual
      care). RESEARCH DESIGN AND METHODS: We performed a cross-sectional, observational
      cohort study of 363 veteran patients with type 2 diabetes and SMI who received
      care from one of three Veterans Affairs medical facilities: two sites that
      provided both collocated and usual care and one site that provided only usual
      care. Through a survey, laboratory tests, and medical records, we assessed
      patient characteristics, glucose control as measured by a current HbA1c, and
      adherence to diabetes medication as measured by the medication possession ration
      (MPR) and self-report. RESULTS: In the sample, the mean HbA1c was 7.4% (57
      mmol/mol), the mean MPR was 80%, and 51% reported perfect adherence to their
      diabetes medications. In both unadjusted and adjusted analyses, there were no
      differences in glucose control and medication adherence by collocation of care.
      Patients seen in collocated care tended to have better HbA1c levels (beta = 
      0.149; P = 0.393) and MPR values (beta = 0.34; P = 0.132) and worse self-reported
      adherence (odds ratio 0.71; P = 0.143), but these were not statistically
      significant. CONCLUSIONS: In a population of veterans with comorbid diabetes and
      SMI, patients on average had good glucose control and medication adherence
      regardless of where they received primary care.

PMID- 24879840
TI  - Markers of platelet activation are increased in adolescents with type 2 diabetes.
AB  - OBJECTIVE: In adults with diabetes, in vivo platelet activation is a marker for
      atherosclerosis and cardiovascular disease (CVD). This pilot study investigated
      whether adolescents with diabetes had evidence of increased in vivo platelet
      activation. RESEARCH DESIGN AND METHODS: In vivo platelet activation was compared
      in four groups of age-matched adolescents: type 1 diabetes (T1D, n = 15), type 2
      diabetes (T2D; n = 15), control subjects with normal BMI (n = 14), and
      overweight/obese control subjects (n = 13). Platelet surface activation markers
      and plasma levels of soluble activation markers were measured and compared among
      groups. RESULTS: Increased expression of all activation markers was observed in
      T2D compared with either control group (P < 0.05); levels of soluble markers were
      also higher in T2D than in T1D (P < 0.05). There were no differences in marker
      expression between the nondiabetic control groups. CONCLUSIONS: Platelet
      activation in adolescents with T2D may be a marker for the risk of CVD
      development in early adulthood.

PMID- 24879841
TI  - Overnight glucose control with an automated, unified safety system in children
      and adolescents with type 1 diabetes at diabetes camp.
AB  - OBJECTIVE: To determine the safety and efficacy of an automated unified safety
      system (USS) in providing overnight closed-loop (OCL) control in children and
      adolescents with type 1 diabetes attending diabetes summer camps. RESEARCH DESIGN
      AND METHODS: The Diabetes Assistant (DIAS) USS used the Dexcom G4 Platinum
      glucose sensor (Dexcom) and t:slim insulin pump (Tandem Diabetes Care). An
      initial inpatient study was completed for 12 participants to evaluate safety. For
      the main camp study, 20 participants with type 1 diabetes were randomized to
      either OCL or sensor-augmented therapy (control conditions) per night over the
      course of a 5- to 6-day diabetes camp. RESULTS: Subjects completed 54 OCL nights
      and 52 control nights. On an intention-to-treat basis, with glucose data analyzed
      regardless of system status, the median percent time in range, from 70-150 mg/dL,
      was 62% (29, 87) for OCL nights versus 55% (25, 80) for sensor-augmented pump
      therapy (P = 0.233). A per-protocol analysis allowed for assessment of algorithm
      performance. The median percent time in range, from 70-150 mg/dL, was 73% (50,
      89) for OCL nights (n = 41) versus 52% (24, 83) for control conditions (n = 39)
      (P = 0.037). There was less time spent in the hypoglycemic range <50, <60, and
      <70 mg/dL during OCL compared with the control period (P = 0.019, P = 0.009, and
      P = 0.023, respectively). CONCLUSIONS: The DIAS USS algorithm is effective in
      improving time spent in range as well as reducing nocturnal hypoglycemia during
      the overnight period in children and adolescents with type 1 diabetes in a
      diabetes camp setting.

PMID- 24879842
TI  - Different lipid variables predict incident coronary artery disease in patients
      with type 1 diabetes with or without diabetic nephropathy: the FinnDiane study.
AB  - OBJECTIVE: To study the ability of lipid variables to predict incident coronary
      artery disease (CAD) events in patients with type 1 diabetes at different stages
      of nephropathy. RESEARCH DESIGN AND METHODS: Patients (n = 3,520) with type 1
      diabetes and available lipid profiles participating in the Finnish Diabetic
      Nephropathy Study (FinnDiane) were included in the study. During a follow-up
      period of 10.2 years (8.6-12.0), 310 patients suffered an incident CAD event.
      RESULTS: Apolipoprotein B (ApoB)/ApoA-I ratio was the strongest predictor of CAD
      in normoalbuminuric patients (hazard ratio 1.43 [95% CI 1.17-1.76] per one SD
      increase), and ApoB was the strongest in macroalbuminuric patients (1.47 [1.19
      1.81]). Similar results were seen when patients were stratified by sex or
      glycemic control. LDL cholesterol was a poor predictor of CAD in women,
      normoalbuminuric patients, and patients with HbA1c below the median (8.3%, 67
      mmol/L). The current recommended triglyceride cutoff of 1.7 mmol/L failed to
      predict CAD in normoalbuminuric patients, whereas the cohort median 0.94 mmol/L
      predicted incident CAD events. CONCLUSIONS: In patients with type 1 diabetes, the
      predictive ability of the lipid variables differed substantially depending on the
      patient's sex, renal status, and glycemic control. In normoalbuminuric patients,
      the ratios of atherogenic and antiatherogenic lipoproteins and lipids were the
      strongest predictors of an incident CAD event, whereas in macroalbuminuric
      patients, no added benefit was gained from the ratios. Current treatment
      recommendations may need to be revised to capture residual CAD risk in patients
      with type 1 diabetes.

PMID- 24879843
TI  - Lower-extremity amputation risk is associated with variation in behavioral risk
      factor surveillance system responses.
AB  - OBJECTIVE: To determine whether regional variation in the rate of lower-extremity
      amputation (LEA) is associated with health behaviors. RESEARCH DESIGN AND
      METHODS: This was a cross-sectional prevalence study of merged data from the U.S.
      Census, Medicare parts A and B, and the Behavioral Risk Factor Surveillance
      System. We used regression models to determine whether previously described
      regional variation in LEA incidence was associated with responses to the
      Behavioral Risk Factor Surveillance System. Regions were created using Dartmouth
      Atlas Health Referral Regions. RESULTS: The mean and median incidence of LEA was
      4.5 per 1,000 persons with diabetes; the rate varied from 2.4 to 7.9 LEA per
      1,000 persons by health referral region. Statistically significant inverse
      associations were found between LEA and the rate of patients reporting colorectal
      screening (P < 0.0001) or the participation in diabetes management classes (P =
      0.018). Most other factors, including daily foot evaluations, were not associated
      with a decreased risk of LEA. These findings were also found to be associated
      with geographically clustered regions known for increased risk of LEA.
      CONCLUSIONS: LEA is known to vary by region in the U.S., and regions with higher
      rates of LEA tend to be clustered together. Some of this variation may be
      explained by health behaviors in those regions, such as attending diabetes
      education classes or better health prevention habits (e.g., colon cancer
      screening). It should be possible to prevent unwanted LEAs by educating
      individuals with diabetes and foot ulcers about the need for participation in
      foot ulcer treatment.

PMID- 24879845
TI  - Expression of hepatic drug-metabolizing cytochrome p450 enzymes and their
      intercorrelations: a meta-analysis.
AB  - Cytochrome P450 is a family of enzymes that catalyze reactions involved in the
      metabolism of drugs and other xenobiotics. These enzymes are therefore important
      in pharmacologic and toxicologic studies, and information on their abundances is
      of value in the process of scaling in vitro data to in vivo metabolic parameters.
      A meta-analysis was applied to data on the abundance of human hepatic cytochrome
      P450 enzymes in Caucasian adult livers (50 studies). Despite variations in the
      methods used to measure the abundance of enzymes, agreement between the studies
      in 26 different laboratories was generally good. Nonetheless, some heterogeneity
      was detected (Higgins and Thompson heterogeneity test). More importantly, large
      interindividual variability was observed in the collated data. Positive
      correlations between the expression levels of some cytochrome P450 enzymes were
      found in the abundance data, including the following pairs: CYP3A4/CYP3A5*1/*3
      (Rs = 0.70, P < 0.0001, n = 52), CYP3A4/CYP2C8 (Rs = 0.68, P < 0.0001, n = 134),
      CYP3A4/CYP2C9 (Rs = 0.55, P < 0.0001, n = 71), and CYP2C8/CYP2C9 (Rs = 0.55, P <
      0.0001, n = 99). These correlations can be used to demonstrate common genetic
      transcriptional mechanisms. 

PMID- 24879844
TI  - Do cardiac biomarkers NT-proBNP and hsTnT predict microvascular events in
      patients with type 2 diabetes? Results from the ADVANCE trial.
AB  - OBJECTIVE: We investigated microvascular event risk in people with type 2
      diabetes and assessed whether N-terminal pro-B-type natriuretic peptide (NT
      proBNP) and high-sensitivity troponin T (hsTnT) improved prediction. RESEARCH
      DESIGN AND METHODS: We performed a case-cohort study, including 439 incident
      cases of microvascular events (new or worsening nephropathy or retinopathy) and
      2,946 noncase subjects identified from participants in the Action in Diabetes and
      Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation
      (ADVANCE) trial. NT-proBNP and hsTnT were measured in stored plasma samples using
      automated commercial assays. RESULTS: After adjustment for age, sex, and
      randomized treatment, the hazard ratios for microvascular events per 1-SD
      increase in the log-transformed hsTnT and NT-proBNP were 1.67 (95% CI 1.51-1.85)
      and 1.63 (1.44-1.84), respectively. After further adjustment for classical and
      diabetes-related cardiovascular disease risk factors, the hazard ratios
      attenuated to 1.40 (1.24-1.58) and 1.41 (1.24-1.60), respectively. While the C
      statistic did not improve on addition of hsTnT or NT-proBNP for the total
      microvascular end point, a combination of both markers improved the prediction of
      nephropathy (P = 0.033) but not retinopathy (P = 0.72). The corresponding net
      reclassification indices in a three-risk category model (<10%, 10-15%, and >15% 5
      year risk) for all microvascular events were 7.31% (95% CI 2.24-12.79) for hsTNT
      addition, 6.23% (1.74-11.5) for NT-proBNP addition, and 7.1% (1.5-12.9) for both
      markers together. CONCLUSIONS: These data suggest that cardiac biomarkers
      moderately improve microvascular event risk prediction, in particular the risk of
      nephropathy. Further studies examining the value of this approach for trial
      design and clinical use are warranted.

PMID- 24879847
TI  - MAA Price Hikes.

PMID- 24879851
TI  - Collaborative 3D Atlas and Brain Development.

PMID- 24879852
TI  - National Health IT Regulatory Strategy Proposed.

PMID- 24879858
TI  - Both predictability and familiarity facilitate contour integration.
AB  - Research has shown that contour detection is impaired in the visual periphery for
      snake-shaped Gabor contours but not for circular and elliptical contours. This
      discrepancy in findings could be due to differences in intrinsic shape
      properties, including shape closure and curvature variation, as well as to
      differences in stimulus predictability and familiarity. In a detection task using
      only circular contours, the target shape is both more familiar and more
      predictable to the observer compared with a detection task in which a different
      snake-shaped contour is presented on each trial. In this study, we investigated
      the effects of stimulus familiarity and predictability on contour integration by
      manipulating and disentangling the familiarity and predictability of snakelike
      stimuli. We manipulated stimulus familiarity by extensively training observers
      with one particular snake shape. Predictability was varied by alternating trial
      blocks with only a single target shape and trial blocks with multiple target
      shapes. Our results show that both predictability and familiarity facilitated
      contour integration, which constitutes novel behavioral evidence for the
      adaptivity of the contour integration mechanism in humans. If familiarity or
      predictability facilitated contour integration in the periphery specifically,
      this could explain the discrepant findings obtained with snake contours as
      compared with circles or ellipses. However, we found that their facilitatory
      effects did not differ between central and peripheral vision and thus cannot
      explain that particular discrepancy in the literature.

PMID- 24879859
TI  - Aging and the integration of orientation and position in shape perception.
AB  - The current experiments examined the effect of healthy aging on the integration
      of orientation and position information in shape perception. Following Day and
      Loffler (2009), conflicting contours were created by sampling the orientations of
      one shape (e.g., a rounded pentagon) with Gabors, and positioning them on the
      circumference of a different shape (e.g., a circle). In Experiment 1, subjects
      judged whether the conflicting contour looked more circular than a rounded
      pentagon of varying amplitude, which allowed us to estimate the perceived shape
      of the conflicting contour. The relative amount of position and orientation
      information was manipulated by varying the number of Gabors comprising the target
      contour. Orientation information dominated the percept for contours sampled with
      15-40 elements, producing a strong shape illusion, but position information
      determined the shape with denser sampling. The magnitude of this orientation
      dominance effect was equal in younger and older subjects across all sampling
      levels. In Experiment 2, subjects discriminated five contours that differed in
      orientation and/or position information. Both groups showed poor discrimination
      between conflicting contours and their perceptually equivalent radial frequency
      patterns, confirming the main finding of Experiment 1. In addition, older
      subjects showed worse discrimination between two noncircular radial frequency
      patterns than younger subjects. In sum, integration of orientation and position
      information in shape perception is preserved with aging; however, older adults
      are less able to make fine shape discriminations between noncircular sampled
      contours.

PMID- 24879856
TI  - Cdk5 activity in the brain - multiple paths of regulation.
AB  - Cyclin dependent kinase-5 (Cdk5), a family member of the cyclin-dependent
      kinases, plays a pivotal role in the central nervous system. During
      embryogenesis, Cdk5 is indispensable for brain development and, in the adult
      brain, it is essential for numerous neuronal processes, including higher
      cognitive functions such as learning and memory formation. However, Cdk5 activity
      becomes deregulated in several neurological disorders, such as Alzheimer's
      disease, Parkinson's disease and Huntington's disease, which leads to
      neurotoxicity. Therefore, precise control over Cdk5 activity is essential for its
      physiological functions. This Commentary covers the various mechanisms of Cdk5
      regulation, including several recently identified protein activators and
      inhibitors of Cdk5 that control its activity in normal and diseased brains. We
      also discuss the autoregulatory activity of Cdk5 and its regulation at the
      transcriptional, post-transcriptional and post-translational levels. We finally
      highlight physiological and pathological roles of Cdk5 in the brain. Specific
      modulation of these protein regulators is expected to provide alternative
      strategies for the development of effective therapeutic interventions that are
      triggered by deregulation of Cdk5. 

PMID- 24879861
TI  - Attenuation of the pupillary response to luminance and color changes during
      interocular suppression.
AB  - The present study investigated the effects of interocular suppression on the
      pupillary constriction to luminance and color changes. Stable interocular
      suppression was produced by presenting a flickering high-contrast grating to one
      eye and a spatially homogeneous field to the other eye. The results showed that
      the pupillary responses to luminance as well as color changes were clearly
      attenuated during interocular suppression; the pupillary constriction to stimulus
      changes was delayed and reduced in amplitude when those changes occurred in the
      suppressed eye. The attenuation of the pupillary response was observed over a
      wide range of test contrast extending to well above the threshold level.
      Moreover, the properties of the suppressive effect were very similar to those
      assessed psychophysically using both detection thresholds for weak stimuli and
      reaction times for suprathreshold stimuli. Overall, the present study provided
      converging evidence that the pupillary response can be a useful objective probe
      of interocular suppression in humans. The results are discussed in view of
      possible differential involvements of subcortical and cortical visual processing
      in driving the pupillary response as well as in interocular suppression.

PMID- 24879860
TI  - Differential effects of visual attention and working memory on binocular rivalry.
AB  - The investigation of cognitive influence on binocular rivalry has a long history.
      However, the effects of visual WM on rivalry have never been studied so far. We
      examined top-down modulation of rivalry perception in four experiments to compare
      the effects of visual WM and sustained selective attention: In the first three
      experiments we failed to observe any sustained effect of the WM content; only the
      color of the memory probe was found to prime the initially dominant percept. In
      Experiment 4 we found a clear effect of sustained attention on rivalry both in
      terms of the first dominant percept and of the overall dominance when
      participants were involved in a tracking task. Our results provide an example of
      dissociation between visual WM and selective attention, two phenomena which
      otherwise functionally overlap to a large extent. Furthermore, our study
      highlights the importance of the task employed to engage cognitive resources: The
      observed perceptual epiphenomena of binocular rivalry are indicative of visual
      competition at an early stage, which is not affected by WM but is still
      susceptible to attention influence as long as the observer's attention is
      constrained to one of the two rival images via a specific concomitant task.

PMID- 24879862
TI  - Saccadic inhibition can cause the remote distractor effect, but the remote
      distractor effect may not be a useful concept.
AB  - We have suggested that the remote distractor effect (RDE), the elevation of
      average saccadic reaction time (SRT) induced by a task-irrelevant distractor, may
      be explained as a statistical consequence of a characteristic reshaping of the
      SRT distribution known as saccadic inhibition (SI; Buonocore & McIntosh, 2008).
      In a recent paper, Walker and Benson (2013) argue against this idea and claim
      that the RDE and SI are partly dissociable. Here, we examine this claim, taking
      the opportunity to clarify potential ambiguities about how SI affects average
      SRT, and how the presence of SI can be inferred from SRT distributions.We
      highlight what we consider to be the most interesting aspects of Walker and
      Benson's data, and suggest that a more flexible and nuanced view of SI can
      account for them. In considering the relation between SI and the RDE, we conclude
      that the RDE may no longer be a useful concept for eye movement researchers.

PMID- 24879864
TI  - The effect of nontemporal stimulus size on perceived duration as assessed by the
      method of reproduction.
AB  - Perceived duration is assumed to be positively related to nontemporal stimulus
      magnitude. Most recently, the finding that larger stimuli are perceived to last
      longer has been challenged to represent a mere decisional bias induced by the use
      of comparative duration judgments. Therefore, in the present study, the method of
      temporal reproduction was applied as a psychophysical procedure to quantify
      perceived duration. Another major goal was to investigate the influence of
      attention on the effect of visual stimulus size on perceived duration. For this
      purpose, an additional dual-task paradigm was employed. Our results not only
      converged with previous findings in demonstrating a functional positive
      relationship between nontemporal stimulus size and perceived duration, but also
      showed that the effect of stimulus size on perceived duration was not confined to
      comparative duration judgments. Furthermore, the effect of stimulus size proved
      to be independent of attentional resources allocated to stimulus size;
      nontemporal visual stimulus information does not need to be processed
      intentionally to influence perceived duration. Finally, the effect of nontemporal
      stimulus size on perceived duration was effectively modulated by the duration of
      the target intervals, suggesting a hitherto largely unrecognized role of temporal
      context for the effect of nontemporal stimulus size to become evident.

PMID- 24879863
TI  - Visual control of an action discrimination in pigeons.
AB  - Recognizing and categorizing behavior is essential for all animals. The visual
      and cognitive mechanisms underlying such action discriminations are not well
      understood, especially in nonhuman animals. To identify the visual bases of
      action discriminations, four pigeons were tested in a go/no-go procedure to
      examine the contribution of different visual features in a discrimination of
      walking and running actions by different digital animal models. Two different
      tests with point-light displays derived from studies of human biological motion
      failed to support transfer of the learned action discrimination from fully
      figured models. Tests with silhouettes, contours, and the selective deletion or
      occlusion of different parts of the models indicated that information about the
      global motions of the entire model was critical to the discrimination. This
      outcome, along with earlier results, suggests that the pigeons' discrimination of
      these locomotive actions involved a generalized categorization of the sequence of
      configural poses. Because the motor systems for locomotion and flying in pigeons
      share little in common with quadruped motions, the pigeons' discrimination of
      these behaviors creates problems for motor theories of action recognition based
      on mirror neurons or related notions of embodied cognition. It suggests instead
      that more general motion and shape mechanisms are sufficient for making such
      discriminations, at least in birds.

PMID- 24879865
TI  - Contour extracting networks in early extrastriate cortex.
AB  - Neurons in the visual cortex process a local region of visual space, but in order
      to adequately analyze natural images, neurons need to interact. The notion of an
      ''association field'' proposes that neurons interact to extract extended
      contours. Here, we identify the site and properties of contour integration
      mechanisms. We used functional magnetic resonance imaging (fMRI) and population
      receptive field (pRF) analyses. We devised pRF mapping stimuli consisting of
      contours. We isolated the contribution of contour integration mechanisms to the
      pRF by manipulating the contour content. This stimulus manipulation led to
      systematic changes in pRF size. Whereas a bank of Gabor filters quantitatively
      explains pRF size changes in V1, only V2/V3 pRF sizes match the predictions of
      the association field. pRF size changes in later visual field maps, hV4, LO-1,
      and LO-2 do not follow either prediction and are probably driven by distinct
      classical receptive field properties or other extraclassical integration
      mechanisms. These pRF changes do not follow conventional fMRI signal strength
      measures. Therefore, analyses of pRF changes provide a novel computational
      neuroimaging approach to investigating neural interactions. We interpreted these
      results as evidence for neural interactions along cooriented, cocircular
      receptive fields in the early extrastriate visual cortex (V2/V3), consistent with
      the notion of a contour association field.

PMID- 24879866
TI  - Research tool: Validation of floxed alpha7 nicotinic acetylcholine receptor
      conditional knockout mice using in vitro and in vivo approaches.
AB  - There is much interest in alpha7 nicotinic acetylcholine receptors (nAChRs) in
      CNS function since they are found throughout peripheral tissues as well as being
      highly expressed in brain regions implicated in attention, learning and memory.
      As such, the role of these receptors in many aspects of CNS function and disease
      is being actively investigated. To date, only one null mouse model (A7KO) is
      available which is non-conditional and constitutive. Since alpha7 nAChRs are
      present on neurons and glia (including astrocytes), as well as being
      developmentally regulated, there is an unmet need for the technical capability to
      control alpha7 nAChR gene expression. Therefore we have generated mice in which
      the fourth exon of the alpha7 nAChR gene (Chrna7) is flanked by loxP sites (B6
      Chrna7(LBDEx4007Ehs)) which we refer to as floxed alpha7 nAChR conditional
      knockout or alpha7nAChR(flox). We validated the chosen approach by mating
      alpha7nAChR(flox) with mice expressing Cre recombinase driven by the glial acidic
      fibrillary protein (GFAP)-Cre promoter (GFAP-A7KO) to test whether
      alpha7nAChR(flox), GFAP-A7KO and appropriate littermate controls performed
      equally in our standard Rodent In Vivo Assessment Core battery to assess general
      health, locomotion, emotional and cognitive behaviours. Neither alpha7nAChR(flox)
      nor GFAP-A7KO exhibited significant differences from littermate controls in any
      of the baseline behavioural assessments we conducted, similar to the 'first
      generation' non-conditional A7KO mice. We also determined that alpha7 nAChR
      binding sites were absent on GFAP-positive astrocytes in hippocampal slices
      obtained from GFAP-A7KO offspring from alpha7nAChR(flox) and GFAP-Cre crosses.
      Finally, we validated that Cre recombinase (Cre)-mediated excision led to
      functional, cell- and tissue-specific loss of alpha7 nAChRs by demonstrating that
      choline-induced alpha7 nAChR currents were present in Cre-negative, but not
      synapsin promoter-driven Cre-positive, CA1 pyramidal neurons. Additionally,
      electrophysiological characterization of alpha7 nAChR-mediated current traces was
      similar in terms of amplitude and time constants of decay (during
      desensitization) for the alpha7nAChR(flox) and wild-type (WT) mice. Thus, we have
      in vivo and in vitro evidence that the Chrna7 exon 4 targeting strategy does not
      alter behavioural, cognitive, or electrophysiological properties compared to WT
      and that Cre-mediated excision is an effective approach to delete alpha7 nAChR
      expression in a cell-specific manner. 

PMID- 24879867
TI  - Utrophin regulates modal gating of mechanosensitive ion channels in dystrophic
      skeletal muscle.
AB  - Dystrophin is a large, submembrane cytoskeletal protein, absence of which causes
      Duchenne muscular dystrophy. Utrophin is a dystrophin homologue found in both
      muscle and brain whose physiological function is unknown. Recordings of single
      channel activity were made from membrane patches on skeletal muscle from mdx,
      mdx/utrn(+/-) heterozygotes and mdx/utrn(-/-) double knockout mice to investigate
      the role of these cytoskeletal proteins in mechanosensitive (MS) channel gating.
      We find complex, gene dose-dependent effects of utrophin depletion in dystrophin
      deficient mdx muscle: (1) increased MS channel open probability, (2) a shift of
      MS channel gating to larger pressures, (3) appearance of modal gating of MS
      channels and small conductance channels and (4) expression of large conductance
      MS channels. We suggest a physical model in which utrophin acts as a scaffolding
      protein that stabilizes lipid microdomains and clusters MS channel subunits.
      Depletion of utrophin disrupts domain composition in a manner that favours open
      channel area expansion, as well as allowing diffusion and aggregation of
      additional MS channel subunits. 

PMID- 24879868
TI  - Diet-dependent modulation of gastro-oesphageal vagal afferent mechanosensitivity
      by endogenous nitric oxide.
AB  - Neuronal nitric oxide (NO) plays an important role in gastric motor activity and
      modulates the mechanosensitivity of gastro-oesophageal vagal afferents. Effects
      of NO on food intake are dependent on feeding status. We sought to determine the
      effect of NO on gastro-oesophageal vagal afferent activity in the normally fed
      and food-restricted states and the second messenger pathways mediating these
      effects. Eight week old female C56BL/6 mice were fed ad libitum or food
      restricted for 14 h. An in vitro preparation was used to determine the functional
      effects of NO and the second messenger pathways involved. Expression of NO signal
      transduction molecules in vagal afferents was determined by reverse-transcription
      polymerase chain reaction (RT-PCR). Endogenous NO and the NO donor S-nitroso-N
      acetylpenicillamine (SNAP) inhibited vagal mucosal afferent responses to tactile
      stimuli in mice fed ad libitum. After a 14 h fast endogenous NO and SNAP
      potentiated tension and mucosal afferent responses to mechanical stimulation. The
      excitatory effect of NO was blocked by the nicotinamide adenine dinucleotide
      phosphate (NADPH) oxidase inhibitor apocynin. After a 14 h fast expression of
      NADPH oxidase 2 (NOX2) mRNA in whole nodose ganglia was significantly reduced and
      the excitatory effect of NO on gastro-oesophageal vagal afferents was lost. Under
      fasting conditions the inhibitory effect of NO was blocked with the
      hyperpolarisation-activated cyclic nucleotide-gated (HCN) channel blocker
      ivabradine and mRNA expression of HCN3 in the nodose ganglia was elevated. In
      conclusion, the role of NO in the peripheral modulation of gastro-oesophageal
      vagal afferents is dynamic and dependent on feeding status. 

PMID- 24879870
TI  - Heterogeneous distribution of exocytotic microdomains in adrenal chromaffin cells
      resolved by high-density diamond ultra-microelectrode arrays.
AB  - Here we describe the ability of a high-density diamond microelectrode array
      targeted to resolve multi-site detection of fast exocytotic events from single
      cells. The array consists of nine boron-doped nanocrystalline diamond ultra
      microelectrodes (9-Ch NCD-UMEA) radially distributed within a circular area of
      the dimensions of a single cell. The device can be operated in voltammetric or
      chronoamperometric configuration. Sensitivity to catecholamines, tested by dose
      response calibrations, set the lowest detectable concentration of adrenaline to
      ~5 MUm. Catecholamine release from bovine or mouse chromaffin cells could be
      triggered by electrical stimulation or external KCl-enriched solutions. Spikes
      detected from the cell apex using carbon fibre microelectrodes showed an
      excellent correspondence with events measured at the bottom of the cell by the 9
      Ch NCD-UMEA, confirming the ability of the array to resolve single quantal
      secretory events. Subcellular localization of exocytosis was provided by
      assigning each quantal event to one of the nine channels based on its location.
      The resulting mapping highlights the heterogeneous distribution of secretory
      activity in cell microdomains of 12-27 MUm2. In bovine chromaffin cells,
      secretion was highly heterogeneous with zones of high and medium activity in 54%
      of the cell surface and zones of low or no activity in the remainder. The 'non
      active' ('silent') zones covered 24% of the total and persisted for 6-8 min,
      indicating stable location. The 9-Ch NCD-UMEA therefore appears suitable for
      investigating the microdomain organization of neurosecretion with high spatial
      resolution.

PMID- 24879869
TI  - P2Y1 receptor-mediated potentiation of inspiratory motor output in neonatal rat
      in vitro.
AB  - PreBotzinger complex inspiratory rhythm-generating networks are excited by
      metabotropic purinergic receptor subtype 1 (P2Y1R) activation. Despite this, and
      the fact that inspiratory MNs express P2Y1Rs, the role of P2Y1Rs in modulating
      motor output is not known for any MN pool. We used rhythmically active brainstem
      spinal cord and medullary slice preparations from neonatal rats to investigate
      the effects of P2Y1R signalling on inspiratory output of phrenic and XII MNs that
      innervate diaphragm and airway muscles, respectively. MRS2365 (P2Y1R agonist, 0.1
      mm) potentiated XII inspiratory burst amplitude by 60 +/- 9%; 10-fold higher
      concentrations potentiated C4 burst amplitude by 25 +/- 7%. In whole-cell voltage
      clamped XII MNs, MRS2365 evoked small inward currents and potentiated spontaneous
      EPSCs and inspiratory synaptic currents, but these effects were absent in TTX at
      resting membrane potential. Voltage ramps revealed a persistent inward current
      (PIC) that was attenuated by: flufenamic acid (FFA), a blocker of the Ca(2+)
      dependent non-selective cation current ICAN; high intracellular concentrations of
      BAPTA, which buffers Ca(2+) increases necessary for activation of ICAN; and 9
      phenanthrol, a selective blocker of TRPM4 channels (candidate for ICAN). Real
      time PCR analysis of mRNA extracted from XII punches and laser-microdissected XII
      MNs revealed the transcript for TRPM4. MRS2365 potentiated the PIC and this
      potentiation was blocked by FFA, which also blocked the MRS2365 potentiation of
      glutamate currents. These data suggest that XII MNs are more sensitive to P2Y1R
      modulation than phrenic MNs and that the P2Y1R potentiation of inspiratory output
      occurs in part via potentiation of TRPM4-mediated ICAN, which amplifies
      inspiratory inputs.

PMID- 24879871
TI  - Cholinergic circuit modulation through differential recruitment of neocortical
      interneuron types during behaviour.
AB  - Acetylcholine is a crucial neuromodulator for attention, learning and memory.
      Release of acetylcholine in primary sensory cortex enhances processing of sensory
      stimuli, and many in vitro studies have pinpointed cellular mechanisms that could
      mediate this effect. In contrast, how cholinergic modulation shapes the function
      of intact circuits during behaviour is only beginning to emerge. Here we review
      recent data on the recruitment of identified interneuron types in neocortex by
      cholinergic signalling, obtained with a combination of genetic targeting of cell
      types, two-photon imaging and optogenetics. These results suggest that
      acetylcholine release during basal forebrain stimulation, and during
      physiological recruitment of the basal forebrain, can strongly and rapidly
      influence the firing of neocortical interneurons. In contrast to the traditional
      view of neuromodulation as a relatively slow process, cholinergic signalling can
      thus rapidly convey time-locked information to neocortex about the behavioural
      state of the animal and the occurrence of salient sensory stimuli. Importantly,
      these effects strongly depend on interneuron type, and different interneuron
      types in turn control distinct aspects of circuit function. One prominent effect
      of phasic acetylcholine release is disinhibition of pyramidal neurons, which can
      facilitate sensory processing and associative learning.

PMID- 24879876
TI  - Evaluating the relative usefulness of old radiological equipment.

PMID- 24879873
TI  - The degree of acute descending control of spinal nociception in an area of
      primary hyperalgesia is dependent on the peripheral domain of afferent input.
AB  - Descending controls of spinal nociceptive processing play a critical role in the
      development of inflammatory hyperalgesia. Acute peripheral nociceptor
      sensitization drives spinal sensitization and activates spino-supraspinal-spinal
      loops leading to descending inhibitory and facilitatory controls of spinal
      neuronal activity that further modify the extent and degree of the pain state.
      The afferent inputs from hairy and glabrous skin are distinct with respect to
      both the profile of primary afferent classes and the degree of their peripheral
      sensitization. It is not known whether these differences in afferent input
      differentially engage descending control systems to different extents or in
      different ways. Injection of complete Freund's adjuvant resulted in inflammation
      and swelling of hairy hind foot skin in rats, a transient thermal hyperalgesia
      lasting <2 h, and longlasting primary mechanical hyperalgesia (>=7 days). Much
      longer lasting thermal hyperalgesia was apparent in glabrous skin (1 h to >72 h).
      In hairy skin, transient hyperalgesia was associated with sensitization of
      withdrawal reflexes to thermal activation of either A- or C-nociceptors. The
      transience of the hyperalgesia was attributable to a rapidly engaged descending
      inhibitory noradrenergic mechanism, which affected withdrawal responses to both A
      and C-nociceptor activation and this could be reversed by intrathecal
      administration of yohimbine (alpha-2-adrenoceptor antagonist). In glabrous skin,
      yohimbine had no effect on an equivalent thermal inflammatory hyperalgesia. We
      conclude that acute inflammation and peripheral nociceptor sensitization in hind
      foot hairy skin, but not glabrous skin, rapidly activates a descending inhibitory
      noradrenergic system. This may result from differences in the engagement of
      descending control systems following sensitization of different primary afferent
      classes that innervate glabrous and hairy skin. 

PMID- 24879872
TI  - Direct excitation of parvalbumin-positive interneurons by M1 muscarinic
      acetylcholine receptors: roles in cellular excitability, inhibitory transmission
      and cognition.
AB  - Parvalbumin-containing (PV) neurons, a major class of GABAergic interneurons, are
      essential circuit elements of learning networks. As levels of acetylcholine rise
      during active learning tasks, PV neurons become increasingly engaged in network
      dynamics. Conversely, impairment of either cholinergic or PV interneuron function
      induces learning deficits. Here, we examined PV interneurons in hippocampus (HC)
      and prefrontal cortex (PFC) and their modulation by muscarinic acetylcholine
      receptors (mAChRs). HC PV cells, visualized by crossing PV-CRE mice with
      Rosa26YFP mice, were anatomically identified as basket cells and PV bistratified
      cells in the stratum pyramidale; in stratum oriens, HC PV cells were
      electrophysiologically distinct from somatostatin-containing cells. With
      glutamatergic transmission pharmacologically blocked, mAChR activation enhanced
      PV cell excitability in both CA1 HC and PFC; however, CA1 HC PV cells exhibited a
      stronger postsynaptic depolarization than PFC PV cells. To delete M1 mAChRs
      genetically from PV interneurons, we created PV-M1 knockout mice by crossing PV
      CRE and floxed M1 mice. The elimination of M1 mAChRs from PV cells diminished M1
      mAChR immunoreactivity and muscarinic excitation of HC PV cells. Selective
      cholinergic activation of HC PV interneurons using Designer Receptors Exclusively
      Activated by Designer Drugs technology enhanced the frequency and amplitude of
      inhibitory synaptic currents in CA1 pyramidal cells. Finally, relative to wild
      type controls, PV-M1 knockout mice exhibited impaired novel object recognition
      and, to a lesser extent, impaired spatial working memory, but reference memory
      remained intact. Therefore, the direct activation of M1 mAChRs on PV cells
      contributes to some forms of learning and memory. 

PMID- 24879874
TI  - Nociceptive primary afferents: they have a mind of their own.
AB  - Nociceptive primary afferents have three surprising properties: they are highly
      complex in their expression of neurotransmitters and receptors and most probably
      participate in autocrine and paracrine interactions; they are capable of exerting
      tonic and activity-dependent inhibitory control over incoming nociceptive input;
      they can generate signals in the form of dorsal root reflexes that are
      transmitted antidromically out to the periphery and these signals can result in
      neurogenic inflammation in the innervated tissue. Thus, nociceptive primary
      afferents are highly complicated structures, capable of modifying input before it
      is ever transmitted to the central nervous system and capable of altering the
      tissue they innervate. 

PMID- 24879877
TI  - For whom?

PMID- 24879878
TI  - Xenia Forsselliana 2012.

PMID- 24879879
TI  - Contrast-enhanced intraoperative ultrasound.

PMID- 24879880
TI  - Response to "contrast-enhanced intraoperative ultrasound".

PMID- 24879881
TI  - The Role of Gravity in Periorbital and Midfacial Aging.
AB  - BACKGROUND: With respect to the pathogenesis of periorbital and midfacial aging,
      gravity may play a greater role than volume loss. OBJECTIVES: The authors
      determined the effect of shifting from the upright to the supine position on
      specific attributes of facial appearance and ascertained whether facial
      appearance in the supine position bore any resemblance to its appearance in
      youth. METHODS: Participants who showed signs of midface aging were positioned in
      the upright and supine positions, and photographs were obtained during smiling
      and repose. For each photograph, examiners graded the following anatomic
      parameters, using a standardized scale: brow position, tear trough length and
      depth, steatoblepharon, cheek volume, malar bags/festoons, and nasolabial folds.
      Some participants provided photographs of themselves taken 10 to 15 years
      earlier; these were compared with the study images. RESULTS: Interobserver
      correlation was strong. When participants were transferred from upright to
      supine, all anatomic parameters examined became more youthful in appearance;
      findings were statistically significant. The grading of anatomic parameters of
      the earlier photographs most closely matched that of current supine photographs
      of the subjects smiling. CONCLUSIONS: In the supine position, as opposed to the
      upright position, participants with signs of midface aging appear to have much
      more volume in the periorbita and midface. For the subset of participants who
      provided photographs obtained 10 to 15 years earlier, the appearance of facial
      volume was similar between those images and the current supine photographs. This
      suggests that volume displacement due to gravitational forces plays an integral
      role in the morphogenesis of midface aging.

PMID- 24879882
TI  - Rib Diced Cartilage-Fascia Grafting in Dorsal Nasal Reconstruction: A Randomized
      Clinical Trial of Wrapping With Rectus Muscle Fascia vs Deep Temporal Fascia.
AB  - BACKGROUND: Rib cartilage is an abundant source for cartilage grafts when
      significant dorsal nasal augmentation or structural support is indicated. Diced
      cartilage wrapped in fascia was developed to counteract warping, visibility, and
      displacement of rib cartilage as a dorsal solid graft. The technique for wrapping
      diced cartilage has evolved during the past several years. OBJECTIVES: The
      authors compared 2 distinct fascial sleeves for wrapping rib diced cartilage in
      the treatment of patients who required major dorsal nasal augmentation. METHODS:
      Thirty-six patients who planned to undergo major dorsal nasal reconstruction with
      diced costal rib cartilage were assigned randomly to 1 of 2 groups: the
      intervention group, which received grafts wrapped with rectus muscle fascia from
      the rib cartilage harvesting site, or the control group, which received deep
      temporal fascia harvested separately. Outcomes were compared between the groups.
      RESULTS: Patients in the intervention group had significantly shorter operating
      times, significantly higher average satisfaction scores, and significantly
      shorter postoperative hospital stays than did patients in the control group.
      CONCLUSIONS: Harvesting rectus muscle fascia for wrapping diced rib cartilage is
      a feasible and reliable technique in dorsal nasal reconstruction surgery. It is
      associated with favorable outcomes and a high level of patient satisfaction.
      LEVEL OF EVIDENCE: 4.

PMID- 24879883
TI  - Palliative Care in the Intensive Care Unit: Are Residents Well Trained to Provide
      Optimal Care to Critically ill Patients?
AB  - Palliative care (PC) and end-of-life (EOL) care are gaining importance in the
      management of critically ill patients in the ICU. Residents form a significant
      work force in the ICU and most often are the only group that provides round the
      clock coverage. METHODS: We conducted a cross sectional study where residents
      were surveyed to assess their knowledge, skills and perceived barriers towards
      palliative care in the ICU. RESULTS: The most common barrier identified by our
      residents was discrepancies in goals of care between the medical team and
      patients/families (18.7%). A palliative care consult was most commonly obtained
      when the patient was terminally ill (22.9%). DISCUSSION: Teaching should focus on
      overcoming the identified barriers especially communication with patients and
      their families. More studies are needed to identify the best method to teach
      Palliative care in the ICU.

PMID- 24879884
TI  - Motivations, Death Anxiety, and Empathy in Hospice Volunteers in France.
AB  - This study examined the motivations for volunteering of hospice volunteers in
      France. In addition, their levels of death anxiety and empathy were measured and
      compared with those of French non-hospice volunteers and non-volunteers. Three
      questionnaires-the Inventory of Motivations for Hospice Palliative Care
      Volunteerism (IMHPCV), the Templer/McMordie Death Anxiety Scale, and the
      Interpersonal Reactivity Index-were sent via an Internet link to 2 hospice
      volunteer associations and to non-hospice volunteers and non-volunteers (only the
      hospice volunteers received the IMHPCV). Altruistic motives had the most
      influence on the respondents' decision to become a hospice volunteer. French
      hospice volunteers scored significantly lower on 3 categories of motives on the
      IMHPCV compared to a sample of Canadian hospice palliative care volunteers (study
      2), suggesting that cultural differences may be involved. No significant
      differences were found in levels of death anxiety or empathy between the 3 groups
      of respondents of the study.

PMID- 24879885
TI  - The impact of nutritional labels and socioeconomic status on energy intake. An
      experimental field study.
AB  - There is some evidence for paradoxical effects of nutritional labelling on energy
      intake particularly amongst restrained eaters and those with a higher body mass
      index (BMI) resulting in greater consumption of energy from foods with a positive
      health message (e.g. "low-fat") compared with the same foods, unlabelled. This
      study aimed to investigate, in a UK general population sample, the likelihood of
      paradoxical effects of nutritional labelling on energy intake. Participants (n =
      287) attended a London cinema and were offered a large tub of salted or toffee
      popcorn. Participants were randomised to receive their selected flavour with one
      of three labels: a green low-fat label, a red high-fat label or no label.
      Participants watched two film clips while completing measures of demographic
      characteristics, emotional state and taste of the popcorn. Following the
      experiment, popcorn consumption was measured. There were no main effects of
      nutritional labelling on consumption. Contrary to predictions neither BMI nor
      weight concern moderated the effect of label on consumption. There was a three
      way interaction between low-fat label, weight concern and socioeconomic status
      (SES) such that weight-concerned participants of higher SES who saw a low-fat
      label consumed more than weight unconcerned participants of similar SES (t = 
      2.7, P = .04). By contrast, weight-concerned participants of lower SES seeing
      either type of label, consumed less than those seeing no label (t = -2.04, P =
      .04). Nutritional labelling may have different effects in different socioeconomic
      groups. Further studies are required to understand fully the possible
      contribution of food labelling to health inequalities. 

PMID- 24879886
TI  - Sweet craving and ghrelin and leptin levels in women during stress.
AB  - Ingesting sweet substances in excess may attenuate the effects of stress in women
      and impact leptin levels, which are also affected by alcohol dependence and
      overeating. Excess intake of sweet substances also influences ghrelin levels,
      involved in the onset of food intake and stress. This paper aimed to identify
      sweet craving (SC) in women with stress to assess how it impacts basal leptin and
      active ghrelin levels, anthropometric measurements, and body composition. This
      observational, transversal study included 57 women and used the Stress Symptoms
      Inventory Lipp in Adults (ISSL); it verified that 31 of the participants were
      stressed, whereas 26 were symptom-free. The Questionnaire for Assessment of Sweet
      Substance Dependence and Abuse helped to characterize SC. ELISA furnished leptin
      and active ghrelin serum levels. HOMA was also evaluated. Electrical bioimpedance
      provided body composition values. Among the women with stress, 77.42% had SC, and
      they behaved differently from women without SC. Women with SC exhibited
      significantly higher basal leptin levels (P < 0.01), but women with and without
      stress did not differ statistically in terms of leptin levels. Active ghrelin
      levels in stressed and non-stressed women and in women with and without SC were
      similar. A larger number of women with SC presented body fat percentage higher
      than 30% (P < 0.04). Stressed women had significantly higher waist circumference
      than non-stressed women (P < 0.02). CONCLUSION: Stressed women are more prone to
      SC, and this condition is associated with increased basal leptin levels, larger
      hip circumference, and altered body composition.

PMID- 24879887
TI  - Enhancing consumer liking of low salt tomato soup over repeated exposure by herb
      and spice seasonings.
AB  - There is strong evidence for the link between high dietary sodium and increased
      risk of cardiovascular disease which drives the need to reduce salt content in
      foods. In this study, herb and spice blends were used to enhance consumer
      acceptability of a low salt tomato soup (0.26% w/w). Subjects (n = 148) scored
      their liking of tomato soup samples over 5 consecutive days. The first and last
      days were pre-and post-exposure visits where all participants rated three tomato
      soup samples; standard, low salt and low salt with added herbs and spices. The
      middle 3 days were the repeated exposure phase where participants were divided
      into three balanced groups; consuming the standard soup, the low salt soup, or
      the low salt soup with added herbs and spices. Reducing salt in the tomato soup
      led to a significant decline in consumer acceptability, and incorporating herbs
      and spices did not lead to an immediate enhancement in liking. However, inclusion
      of herbs and spices enhanced the perception of the salty taste of the low salt
      soup to the same level as the standard. Repeated exposure to the herbs and spice
      modified soup led to a significant increase in the overall liking and liking of
      flavour, texture and aftertaste of the soup, whereas no changes in liking were
      observed for the standard and low salt tomato soups over repeated exposure.
      Moreover, a positive trend in increasing the post-exposure liking of the herbs
      and spices soup was observed. The findings suggest that the use of herbs and
      spices is a useful approach to reduce salt content in foods; however, herbs and
      spices should be chosen carefully to complement the food as large contrasts in
      flavour can polarise consumer liking. 

PMID- 24879888
TI  - Labeling exercise fat-burning increases post-exercise food consumption in self
      imposed exercisers.
AB  - The goal of the study was to determine whether the label given to an exercise
      bout affects immediate post-exercise food intake. The authors hypothesized that
      explicitly labeling an exercise bout 'fat-burning' (vs. labeling an exercise bout
      'endurance' exercise) would increase post-exercise food intake in individuals who
      self-impose physical activity, because they are more likely to see the label as
      signal of activated fat metabolism and license to reward oneself. No such effect
      was expected for individuals who do not self-impose physical activity but
      consider exercise enjoyable. Ninety-six participants took part in an experiment
      manipulating the label given to an exercise bout (fat-burning exercise or
      endurance exercise) between participants. They cycled on an ergometer for 20
      minutes at a consistent work rate (55-65% of predicted VO2 max) and were offered
      ad libitum food (i.e., pretzel pieces) after the exercise bout. The results
      showed that self-imposed exercisers, that is, individuals with low behavioral
      regulation and individuals with high psychological distress, high fatigue levels,
      and low positive well-being when exercising, ate more food after exercise when
      the bout was labeled fat-burning exercise rather than endurance exercise. The
      results help develop health interventions, indicating that the tendency to
      compensate for energy expended following physical activity depends on both the
      label given to the exercise bout and the degree to which individuals self-impose
      physical activity. 

PMID- 24879889
TI  - Physical activity motivation mediates the association between depression symptoms
      and moderate-to-vigorous physical activity.
AB  - OBJECTIVE: To test if motivational regulations (i.e., amotivation, external,
      introjected, identified, and intrinsic) mediate the association between
      depression symptoms and moderate-to-vigorous physical activity (MVPA) in young
      adults. METHOD: A total of 319 young adults from Montreal, Quebec participating
      in the Nicotine Dependence in Teens (NDIT) study provided self-report data on
      depression symptoms at age 20 (SD=0.7 years) and motivational regulations at age
      24 (SD=0.7 years). MVPA was assessed using a self-report questionnaire at age 20
      (i.e., at the same time motivation was measured) and using accelerometers one
      month later. Multiple mediation analysis with bootstrapping was employed to
      analyze the data. RESULTS: Controlling for age, sex and self-reported MVPA at age
      20 years; introjected regulation was a significant mediator of the association
      between depression symptoms and MVPA (R(2) adj=0.12; point estimate=-0.0011; BCa
      CI=-0.15 to -0.01). CONCLUSION: Depression symptoms may undermine controlling
      forms of motivation, resulting in decreased MVPA. Intervention strategies may be
      needed to address depression symptoms in young adults to promote sustained MVPA.

PMID- 24879890
TI  - Posttraumatic stress disorder and new-onset diabetes among adult survivors of the
      World Trade Center disaster.
AB  - OBJECTIVE: To explore the temporal relationship between 9/11-related
      posttraumatic stress disorder (PTSD) and new-onset diabetes in World Trade Center
      (WTC) survivors up to 11 years after the attack in 2001. METHODS: Three waves of
      surveys (conducted from 2003 to 2012) from the WTC Health Registry cohort
      collected data on physical and mental health status, sociodemographic
      characteristics, and 9/11-related exposures. Diabetes was defined as self
      reported, physician-diagnosed diabetes reported after enrollment. After excluding
      prevalent cases, there were 36,899 eligible adult enrollees. Logistic regression
      and generalized multilevel growth models were used to assess the association
      between PTSD measured at enrollment and subsequent diabetes. RESULTS: We
      identified 2143 cases of diabetes. After adjustment, we observed a significant
      association between PTSD and diabetes in the logistic model [adjusted odds ratio
      (AOR) 1.28, 95% confidence interval (CI) 1.14-1.44]. Results from the growth
      model were similar (AOR 1.37, 95% CI 1.23-1.52). CONCLUSION: This exploratory
      study found that PTSD, a common 9/11-related health outcome, was a risk factor
      for self-reported diabetes. Clinicians treating survivors of both the WTC attacks
      and other disasters should be aware that diabetes may be a long-term consequence.

PMID- 24879891
TI  - Maternal work conditions, socioeconomic and educational status, and vaccination
      of children: a community-based household survey in Japan.
AB  - OBJECTIVE: This study examined how maternal work-related factors, including the
      availability of paid maternal leave, affect childhood vaccination status.
      Relatively little is known about the association between the employment status of
      mothers and the vaccination status of their children. METHOD: We examined data
      from the Japanese Study on Stratification, Health, Income, and Neighborhood (J
      SHINE), an ongoing epidemiologic household panel study in Japan. We used surveys
      taken in 2010-2011 in this study. RESULTS: We found that mothers who returned to
      work after giving birth were much less likely to follow recommended vaccine
      schedules for their children compared with mothers who stayed at home and those
      who had left the workforce by the time of childbirth. However, taking parental
      leave significantly reduced the risk of not being up-to-date with the vaccination
      schedule at 36 months of age. We also found that children whose mother was
      younger and less educated, and those from an economically deprived family were at
      a high risk of not being up-to-date with the vaccination status at 36 months of
      age. CONCLUSION: Because vaccination is free and widely available in Japan, our
      findings indicate that provision of free vaccinations is not sufficient to
      achieve high vaccination rates.

PMID- 24879892
TI  - Is screen-and-treat approach suited for screening and management of precancerous
      cervical lesions in Sub-Saharan Africa?
AB  - The World Health Organization guidelines for screening and management of cervical
      precancerous lesions updated in 2013 made an emphasis on the use of the 'screen
      and-treat' approach for cervical cancer prevention. In order to facilitate
      scaling-up in low income settings, most of these screen-and-treat strategies do
      not involve confirmatory biopsy. This yields a certain rate of overtreatment. In
      other words, a majority of people undergoing screen-and-treat intervention who
      are treated does not necessarily benefit from the treatment. Therefore, the issue
      of potential short term and long term complications of the recommended treatment
      procedures (cryotherapy and Loop Electrosurgical Excision Procedure) arises. This
      question has seldom been studied in resource poor countries, particularly in Sub
      Saharan Africa where Human Immunodeficiency Virus infection is rampant in an
      epidemic fashion and where the procreative capacities are socially rewarding for
      women. We draw the attention of the scientific community and policy makers to the
      fact that the lack of evidence supporting the safety of these treatment
      procedures in African populations may have an impact on the acceptability of
      these strategies and therefore on the effectiveness of screening programs. 

PMID- 24879893
TI  - Agouti signalling protein is an inverse agonist to the wildtype and agonist to
      the melanic variant of the melanocortin-1 receptor in the grey squirrel (Sciurus
      carolinensis).
AB  - The melanocortin-1 receptor (MC1R) is a key regulator of mammalian pigmentation.
      Melanism in the grey squirrel is associated with an eight amino acid deletion in
      the mutant melanocortin-1 receptor with 24 base pair deletion (MC1RDelta24)
      variant. We demonstrate that the MC1RDelta24 exhibits a higher basal activity
      than the wildtype MC1R (MC1R-wt). We demonstrate that agouti signalling protein
      (ASIP) is an inverse agonist to the MC1R-wt but is an agonist to the MC1RDelta24.
      We conclude that the deletion in the MC1RDelta24 leads to a receptor with a high
      basal activity which is further activated by ASIP. This is the first report of
      ASIP acting as an agonist to MC1R. 

PMID- 24879894
TI  - Dapper-1 is essential for Wnt5a induced cardiomyocyte hypertrophy by regulating
      the Wnt/PCP pathway.
AB  - The Wnt signaling pathway was identified as crucial mediator of cardiomyocyte
      hypertrophy. In this study we found that activation of non-canonical Wnt
      signaling by Wnt5a stimulates protein synthesis and enlargement of cardiomyocyte
      surface area. These hypertrophic features were inhibited in Dapper-1 (Dpr1)
      depleted cells. On the molecular level, we observed inhibition of the non
      canonical Wnt/planar-cell-polarity (PCP) pathway denoted by reduction of c-jun-n
      terminal-kinase (JNK) phosphorylation. Upstream of JNK, increased protein levels
      of the Wnt/PCP trans-membrane receptor van-Gogh-like-2 (Vangl2) were observed
      along with an enrichment of Vangl2 in perinuclear located vesicles. The findings
      suggest that Dpr1 is essential for execution of the Wnt/PCP pathway and
      regulation of the Vangl2/JNK axis. Depletion of Dpr1 inhibits non-canonical Wnt
      signaling induced cardiomyocyte hypertrophy by blocking Wnt/PCP signaling. 

PMID- 24879896
TI  - Rheumatic manifestations in brazilian patients with AIDS.
AB  - INTRODUCTION: Patients with AIDS (acquired immunodeficiency syndrome) may have
      rheumatic complaints such as arthritis and arthralgia, dry eyes, increased
      salivary glands, lower back pain, enthesitis etc. Autoantibodies like ANA
      (antinuclear antibody) and RF (rheumatoid factor) may also be present. OBJECTIVE:
      To study the prevalence of rheumatic complaints in AIDS patients and correlate
      them with the presence of ANA and RF. METHODS: We studied 69 patients with AIDS
      (28.9% women and 71.0% men) with a mean age of 40.8 +/- 8.9 years, median disease
      duration of 60 months, for rheumatic complaints, ANA, ENA-6 (anti-Ro, anti-La,
      anti-Sm, anti-RNP, anti-Scl70 and anti-Jo1) and RF. We collected demographic
      data, CD4+ and CD8+ cell count and values of viral load. RESULTS: Arthralgia was
      present in 39.1%, sicca symptoms in 21.7%, inflammatory lumbar pain in 13.4%,
      enthesopathy in 6.6%, parotid enlargement in 1.4%, RF in 10.1% and ANA in 8.6%.
      All patients were negative for ENA-6. ANA was more common in older patients (p =
      0.03) and in those with higher viral load (p = 0.006). No association was found
      with the presence of RF. CONCLUSIONS: The most common manifestation in this
      context was arthralgia. ANA presence was associated with age of the patients and
      viral load.

PMID- 24879895
TI  - PEX14 binding to Arabidopsis PEX5 has differential effects on PTS1 and PTS2 cargo
      occupancy of the receptor.
AB  - PEX5 acts as a cycling receptor for import of PTS1 proteins into peroxisomes and
      as a co-receptor for PEX7, the PTS2 receptor, but the mechanism of cargo
      unloading has remained obscure. Using recombinant protein domains we show PEX5
      binding to the PEX14N-terminal domain (PEX14N) has no effect on the affinity of
      PEX5 for a PTS1 containing peptide. PEX5 can form a complex containing both
      recombinant PTS1 cargo and endogenous PEX7-thiolase simultaneously but isolation
      of the complex via the PEX14 construct resulted in an absence of thiolase,
      suggesting a possible role for PEX14 in the unloading of PTS2 cargos. 

PMID- 24879897
TI  - Multi-label classification of chronically ill patients with bag of words and
      supervised dimensionality reduction algorithms.
AB  - OBJECTIVE: This research is motivated by the issue of classifying illnesses of
      chronically ill patients for decision support in clinical settings. Our main
      objective is to propose multi-label classification of multivariate time series
      contained in medical records of chronically ill patients, by means of
      quantization methods, such as bag of words (BoW), and multi-label classification
      algorithms. Our second objective is to compare supervised dimensionality
      reduction techniques to state-of-the-art multi-label classification algorithms.
      The hypothesis is that kernel methods and locality preserving projections make
      such algorithms good candidates to study multi-label medical time series.
      METHODS: We combine BoW and supervised dimensionality reduction algorithms to
      perform multi-label classification on health records of chronically ill patients.
      The considered algorithms are compared with state-of-the-art multi-label
      classifiers in two real world datasets. Portavita dataset contains 525 diabetes
      type 2 (DT2) patients, with co-morbidities of DT2 such as hypertension,
      dyslipidemia, and microvascular or macrovascular issues. MIMIC II dataset
      contains 2635 patients affected by thyroid disease, diabetes mellitus, lipoid
      metabolism disease, fluid electrolyte disease, hypertensive disease, thrombosis,
      hypotension, chronic obstructive pulmonary disease (COPD), liver disease and
      kidney disease. The algorithms are evaluated using multi-label evaluation metrics
      such as hamming loss, one error, coverage, ranking loss, and average precision.
      RESULTS: Non-linear dimensionality reduction approaches behave well on medical
      time series quantized using the BoW algorithm, with results comparable to state
      of-the-art multi-label classification algorithms. Chaining the projected features
      has a positive impact on the performance of the algorithm with respect to pure
      binary relevance approaches. CONCLUSIONS: The evaluation highlights the
      feasibility of representing medical health records using the BoW for multi-label
      classification tasks. The study also highlights that dimensionality reduction
      algorithms based on kernel methods, locality preserving projections or both are
      good candidates to deal with multi-label classification tasks in medical time
      series with many missing values and high label density.

PMID- 24879898
TI  - Disassociation for electronic health record privacy.
AB  - The dissemination of Electronic Health Record (EHR) data, beyond the originating
      healthcare institutions, can enable large-scale, low-cost medical studies that
      have the potential to improve public health. Thus, funding bodies, such as the
      National Institutes of Health (NIH) in the U.S., encourage or require the
      dissemination of EHR data, and a growing number of innovative medical
      investigations are being performed using such data. However, simply disseminating
      EHR data, after removing identifying information, may risk privacy, as patients
      can still be linked with their record, based on diagnosis codes. This paper
      proposes the first approach that prevents this type of data linkage using
      disassociation, an operation that transforms records by splitting them into
      carefully selected subsets. Our approach preserves privacy with significantly
      lower data utility loss than existing methods and does not require data owners to
      specify diagnosis codes that may lead to identity disclosure, as these methods
      do. Consequently, it can be employed when data need to be shared broadly and be
      used in studies, beyond the intended ones. Through extensive experiments using
      EHR data, we demonstrate that our method can construct data that are highly
      useful for supporting various types of clinical case count studies and general
      medical analysis tasks. 

PMID- 24879899
TI  - Sesquiterpene acids from Shellac and their bioactivities evaluation.
AB  - Seven sesquiterpenes, including four alpha-cedrene types (Shellolic acid A-C,
      Laccishellolic acid), two R-curcumene types (Shellolic acid D-E) and Shellolic
      acid F were isolated from Shellac, of which six were unknown. Their structures
      were elucidated by HR-ESI-MS, UV, IR, 1D and 2D NMR methods. The absolute
      configurations were confirmed via the Mosher's method, circular dichroism (CD)
      and optical rotation analyses. A plausible biogenetic relationship for 1-6 is
      proposed. Cytotoxic and anti-bacterial activities of the isolates were evaluated.
      To the best of our knowledge, none compounds showed any cytotoxic activity, which
      is well consistent with that Shellac used as nontoxic material in pharmaceutical
      formulations and food additives. However, compound 1 exhibited inhibitory
      activity against Bacillus subtilis with the MIC value of 0.1 mg/mL.

PMID- 24879900
TI  - Silymarin and its constituents in cardiac preconditioning.
AB  - Silymarin, a standardised extract of Silybum marianum (milk thistle), comprises
      mainly of silybin, with dehydrosilybin (DHSB), quercetin, taxifolin, silychristin
      and a number of other compounds which are known to possess a range of salutary
      effects. Indeed, there is evidence for their role in reducing tumour growth,
      preventing liver toxicity, and protecting a number of organs against ischemic
      damage. The hepatoprotective effects of silymarin, especially in preventing
      Amanita and alcohol intoxication induced damage to the liver, are a well
      established fact. Likewise, there is weighty evidence that silymarin possesses
      antimicrobial and anticancer activities. Additionally, it has emerged that in
      animal models, silymarin can protect the heart, brain, liver and kidneys against
      ischemia reperfusion injury, probably by preconditioning. The mechanisms of
      preconditioning are, in general, well studied, especially in the heart. On the
      other hand, the mechanism by which silymarin protects the heart from ischemia
      remains largely unexplored. This review, therefore, focuses on evaluating
      existing studies on silymarin induced cardioprotection in the context of the
      established mechanisms of preconditioning. 

PMID- 24879901
TI  - Isolation and identification of phase I metabolites of phillyrin in rats.
AB  - Phillyrin was one of the main chemical constituents of the fruit of Forsythia
      suspensa (Thunb.) Vahl. It showed various bioactivities including antioxidant and
      anti-inflammatory activities. However, the metabolism of phillyrin remained
      unknown. This report described the isolation and identification of phase I
      metabolites of phillyrin in rats. Nine metabolites including six new ones were
      isolated by various column chromatographies and high-performance liquid
      chromatography. Their structures were elucidated by extensive spectroscopic
      analysis. The antiviral activities of phillyrin and the metabolites were
      evaluated against influenza A (H3N2) virus. Among them, one metabolite M8 showed
      moderate activity with the IC50 value of 26.39 MUM, and three metabolites (M2,
      M3, M9) showed weak antiviral activities at the concentration of 100 MUM. Based
      on the structures of the metabolites, possible metabolic pathways of phillyrin in
      rats were also proposed.

PMID- 24879902
TI  - Cardiac glycosides from the bark of Antiaris toxicaria.
AB  - Five new cardiac glycosides (1-5, namely antiaroside Y-ZC) together with 19 known
      compounds were obtained from the bark of Antiaris toxicaria. Their chemical
      structures were determined by IR, HR-ESI-MS, 1D and 2D NMR (HSQC, (1)H-(1)H COSY,
      HMBC, ROESY). The absolute configuration of sugar unit was defined by acid
      hydrolysis and appropriate derivatization. Compound 1 was rare 5beta-H-10beta-H
      19-nor-cardenolide, which might derive from decarboxylative derivative of 19-COOH
      cardenolide. The inhibitory effects of cardiac glycosides 1-11 on the viability
      of NIH-H460 lung cancer cells and their induction of Nur77 expression were
      evaluated and preliminary structure-activity relationship (SAR) was also
      discussed. 

PMID- 24879903
TI  - The antibiofilm activity of lingonberry flavonoids against oral pathogens is a
      case connected to residual complexity.
AB  - The antimicrobial activity of lingonberry (Vaccinium vitis-idaea L.) was
      evaluated against two oral pathogens, Streptococcus mutans and Fusobacterium
      nucleatum. Long-bed gel permeation chromatography (GPC; Sephadex LH-20) yielded
      purified flavonoids, with the most efficient minimum inhibitory concentrations
      (MICs) against planktonic cells in the anthocyanin and procyanidin primary
      fractions against F. nucleatum (63-125 MUg/ml) and in the procyanidin rich
      fraction against S. mutans (16-31 MUg/ml). The purified flavonol glycosides and
      procyanidins inhibited biofilm formation of S. mutans (MICs 16-31 MUg/ml), while
      the corresponding reference compounds showed no activity. Secondary GPC
      purification yielded flavonol glycosides devoid of antibiofilm activity in the
      50% MeOH fraction, while elution with 70% acetone recovered a brownish material
      with activity against S. mutans biofilm (MIC 8 MUg/ml). Even after HPLC-PDA, NMR,
      and MALDI-TOF analyses, the structural identity of this material remained
      unknown, while its color and analytical characteristics appear to be consistent
      with flavonoid oxidation products.

PMID- 24879904
TI  - Tigliane diterpenes from Croton mauritianus as inhibitors of chikungunya virus
      replication.
AB  - A bioassay-guided purification of an EtOAc extract of the leaves of Croton
      mauritianus using a chikungunya virus-cell-based assay led to the isolation of 12
      O-decanoylphorbol-13-acetate (1) and the new 12-O-decanoyl-7-hydroperoxy-phorbol
      5-ene-13-acetate (2), along with loliolide, vomifoliol, dehydrovomifoliol,
      annuionone D and bluemol C. The planar structure and the relative configuration
      of compound 2 were elucidated based on spectroscopic analysis, including 1D- and
      2D-NMR experiments, mass spectrometry, and comparison with literature data.
      Compounds 1 and 2 inhibited chikungunya virus-induced cell death in cell culture
      with EC50s of 2.4+/-0.3 and 4.0+/-0.8 MUM, respectively.

PMID- 24879905
TI  - Therapeutic targeting of autophagy in cancer. Part I: molecular pathways
      controlling autophagy.
AB  - Autophagy is a process in which cells can generate energy and building materials,
      by degradation of redundant and/or damaged organelles and proteins. Especially
      during conditions of stress, autophagy helps to maintain homeostasis. In
      addition, autophagy has been shown to influence malignant transformation and
      cancer progression. The precise molecular events in autophagy are complex and the
      core autophagic machinery described to date consists of nearly thirty proteins.
      Apart from these factors that execute the process of autophagy, several
      signalling pathways are involved in converting internal and external stimuli into
      an autophagic response. In this review we provide an overview of the signalling
      pathways that influence autophagy, particularly in cancer cells. We will
      illustrate that interference with multiple of these signalling pathways can have
      significant effects on cancer cell survival. 

PMID- 24879908
TI  - Enlarged pupillary membranes.

PMID- 24879909
TI  - CROSS-CULTURAL VALIDATION OF THE PORTUGUESE VERSION OF THE EDUCATIONAL NEEDS
      ASSESSMENT TOOL (PortENAT).
AB  - OBJECTIVES: To undertake a cross-cultural adaptation and validation of the
      educational needs assessment tool (ENAT) into Portuguese. METHODS: The first
      phase of this research (cross-cultural adaptation) utilised a well-established
      translation method comprising five sequential steps: forward-translation,
      synthesis of translations, back-translation, expert committee and field-testing
      of the adapted version. The second phase involved collecting data from 123
      patients and subjecting them to Rasch analysis for validity testing including
      cross-cultural invariance. RESULTS: The translation and field-testing phase went
      smoothly giving rise to minor adjustments in the phrasing of some items. The
      preliminary analysis of the 39 items, revealed some deviations from the model
      with the overall item-person interaction fit statistics ?2(df) = 56.025 (39), p =
      0.038. Significant item-item correlations caused artificial inflation of the
      internal consistency, therefore violating the model assumption of local
      independence of items. To correct this, all locally dependent items were then
      grouped into their respective domains, creating a 7 testlet-scale which
      demonstrated a good fit to the Rasch model, ?2(df) = 2.625 (7), p = 0.917 and
      internal consistency PSI = 0.975. Analysis of the pooled (Portuguese and the
      English) data revealed cross-cultural DIF, requiring adjustments in two testlets:
      'treatments' and 'support' which ensured cross-cultural equivalence. CONCLUSIONS:
      This study confirms the Portuguese ENAT is a robust unidimensional tool with
      which to assess the educational needs of Portuguese people with RA. Cross
      cultural adjustments are required only if the data from Portugal and the UK are
      pooled or compared. The tool is now available for use in clinical practice and
      research.

PMID- 24879916
TI  - Shared genetic factors underlie chronic pain syndromes.
AB  - Chronic pain syndromes (CPS) are highly prevalent in the general population, and
      increasingly the evidence points to a common etiological pathway. Using a large
      cohort of twins (n=8564) characterized for chronic widespread musculoskeletal
      pain (CWP), chronic pelvic pain (PP), migraine (MIG), dry eye disease, and
      irritable bowel syndrome (IBS), we explored the underlying genetic and
      environmental factors contributing to CPS and the correlation between them. The
      sample was predominantly female (87.3%), with a mean age of 54.7 (+/-14.7) years.
      Prevalence of the different CPS ranged from 7.4% (PP) to 15.7% (MIG). For all CPS
      the within-twin correlation in monozygotic twin pairs was higher than in
      dizygotic pairs, suggesting a heritable component. Estimated heritability ranged
      from 19% (IBS) to 46% (PP). Except for MIG, we found significant pairwise
      phenotypic correlations between the CPS. The phenotypic correlation was highest
      between CWP and IBS (0.40; 95% confidence interval: 0.27 to 0.46). Excluding MIG
      from further analyses, cross-twin cross-trait correlations were higher in
      monozygotic compared with dizygotic twin pairs, suggestive of shared genetic
      factors between CWP, PP, IBS, and dry eye disease. Twin modeling analysis
      revealed the common pathway model as the model best explaining the observed
      pattern of correlation between the traits, with an estimated heritability of 66%
      of the underlying latent variable. These results are evidence of shared genetic
      factors in conditions manifesting chronic pain and justify the search for
      underlying genetic variants. 

PMID- 24879917
TI  - The effect of Helicobacter pylori CagA on the HER-2 copy number and expression in
      gastric cancer.
AB  - We investigated whether Helicobacter pylori (H. pylori) CagA contributes to the
      DNA copy change and mRNA transcript expression of the HER-2 gene and,
      consequently, affects HER-2 protein expression to evaluate the significance of
      CagA and HER-2 amplification in gastric cancer. We used the AGS and MKN1 gastric
      cancer and HFE-145 immortalized non-neoplastic gastric mucosa cell lines. We also
      confirmed the effects of CagA on HER-2 expression in human gastric cancer tissues
      and gastric mucosal tissues of H. pylori infected C57BL/6 mice. Ectopic CagA
      expression in AGS, MKN1 and HFE-145 cells showed a significant increase in HER-2
      gene copy number and expression. The gastric mucosae of H. pylori infected
      C57BL/6 mice also showed increased HER-2 DNA copy number and protein expression.
      In addition, CagA expression was detected in 17 (56.7%) of 30 gastric cancer
      tissues, and eight (47%) of them showed HER-2 DNA amplification of more than two
      fold. In immunohistochemistry, HER-2 overexpression was detected in 12 (40%) of
      30 gastric cancers and a positive correlation was observed among DNA copy number,
      the mRNA transcript, and protein expression of the HER-2 gene in gastric cancer
      (P<0.05). These results suggest that H. pylori CagA may induce overexpression of
      the HER-2 protein by increasing HER-2 DNA and mRNA copy number. 

PMID- 24879919
TI  - Diversified targets of FKBP25 and its complex with rapamycin.
AB  - FKBP25 is a member of the super-family of peptidylprolyl cis/trans isomerases,
      which is a high affinity binder for the immunosuppressive antibiotic rapamycin
      (Rpm). FKBP25 isolated from natural sources, its recombinant murine homologue
      (mFKBP25) and their complexes with rapamycin bind to diverse DNAs, RNAs and
      heparin affinity beads. The recombinant mFKBP25/rapamycin complex binds to
      several proteins including the calcineurin-A/calcineurin-B/calmodulin complex and
      to elongation factor 1beta. We solved the X-ray structure of the C-terminal
      domain of mFKBP25 bound to rapamycin that has a higher resolution than of its
      human counterpart, and which clearly illustrates that the positively charged 40s
      loop is an epitope of the FK506-like binding domain (FKBD) for interactions with
      various biopolymers. 

PMID- 24879918
TI  - A cytosolic glutathione s-transferase, GST-theta from freshwater prawn
      Macrobrachium rosenbergii: molecular and biochemical properties.
AB  - Glutathione S-transferases play an important role in cellular detoxification and
      may have evolved to protect cells against reactive oxygen metabolites. In this
      study, we report the molecular characterization of glutathione s-transferase
      theta (GST-theta) from freshwater prawn Macrobrachium rosenbergii. A full length
      cDNA of GSTT (1417 base pairs) was isolated and characterized bioinformatically.
      Exposure to virus (white spot syndrome baculovirus or M. rosenbergii nodovirus),
      bacteria (Aeromonas hydrophila or Vibrio harveyi) or heavy metals (cadmium or
      lead) significantly increased the expression of GSTT (P<0.05) in hepatopancreas.
      Recombinant GST-theta with monochlorobimane substrate had an optimum activity at
      pH7.5 and 35  degrees C. Furthermore recombinant GST-theta activity was abolished
      by the denaturants triton X-100, Gua-HCl, Gua-thiocyanate, SDS and urea in a dose
      dependent manner. Overall, the results suggest a potential role for M.
      rosenbergii GST-theta in detoxification and possibly conferring immune
      protection.

PMID- 24879920
TI  - Optimized production of Serratia marcescens B742 mutants for preparing chitin
      from shrimp shells powders.
AB  - To improve the deproteinization (DP) efficacy of shrimp shell powders (SSP) for
      preparing chitin, Serratia marcescens B742 mutants were prepared using 2% diethyl
      sulfate (DES), UV-irradiation, and/or microwave heating treatments. Both single
      stage and multi-stage mutations were investigated for optimizing S. marcescens
      B742 mutation conditions. Under the optimized mutation conditions (2% DES
      treatment for 30min plus successive 20min UV-irradiation), the protease and
      chitosanase activity produced by mutant S. marcescens B742 was 240.15 and
      170.6mU/mL, respectively, as compared with 212.58+/-1.51 and 83.75+/-6.51mU/mL,
      respectively, by wild S. marcescens B742. DP efficacy of SSP by mutant S.
      marcescens B742 reached 91.4+/-4.6% after 3d of submerged fermentation instead of
      83.4+/-4.7% from the wild S. marcescens B742 after 4d of submerged fermentation.
      Molecular mass of chitosanase and protease was 41.20 and 47.10kDa, respectively,
      and both enzymes were verified by mass spectrometry analysis. The chitosanase
      from both wild and mutant S. marcescens B742 was activated by sodium dodecyl
      sulfate (SDS), Tween 20, Tween 40, and Triton-100, and the protease and
      chitosanase were strongly inhibited by ethylenediaminetetraacetic acid (EDTA).
      These results suggested that S. marcescens B742 mutants can be used in the
      biological production of chitin through deproteinization of SSP. 

PMID- 24879921
TI  - Oral absorption of a valsartan-loaded spray-dried emulsion based on
      hydroxypropylmethyl cellulose.
AB  - The aim of this study was to develop a novel valsartan-loaded spray-dried
      emulsion based on hydroxypropylmethyl cellulose (HPMC) with enhanced oral
      absorption. The valsartan-loaded redispersible dry emulsion was prepared by using
      a high-pressure homogenization and spray-drying process with water, Capryol 90,
      HPMC, and different surfactants, based on the results of the solubility study.
      The spray-dried emulsions formed small and homogeneous emulsions with a mean
      droplet emulsion size ranging from 133.5 to 152.5nm at the dispersion state in
      water. The valsartan-loaded redispersible dry emulsion with HPMC/poloxamer 407
      showed enhanced pH-independent valsartan release, resulting in a dramatically
      enhanced oral bioavailability of valsartan compared to the raw material and
      commercial product. Therefore, a formulation strategy using the redispersible dry
      emulsion with HPMC/poloxamer 407 is very effective for the development of a new
      dosage form containing valsartan. 

PMID- 24879922
TI  - Methylglyoxal mediated conformational changes in histone H2A-generation of
      carboxyethylated advanced glycation end products.
AB  - Methylglyoxal, an oxo-aldehyde has been implicated as a potential precursor in
      non enzymatic glycation reactions. Its role in the modification of extra cellular
      proteins has been extensively reported, but little is known about its
      modification of nuclear proteins, like histones. Here, we report the
      methylglyoxal induced modification of histone H2A which forms an essential part
      of intact core nucleosome. In this study commercially available histone H2A was
      subjected to in vitro non-enzymatic glycation by methylglyoxal. The structural
      alterations in the histone were characterised by various biophysical and
      biochemical techniques. The modified histone showed hyperchromicity at 276nm,
      loss in intrinsic tyrosine fluorescence intensity at 305nm along with a red
      shift, cross linking and dimer formation in SDS PAGE, induction of alpha-helix in
      CD spectroscopy, reduced hydrophobicity in ANS binding studies, accumulation of
      AGE products, increased carbonyl content, and appearance of a novel peak showing
      carboxyethylation complemented by a shift in amide I and amide II bands in ATR
      FTIR spectroscopy. The modified histone exhibited increased melting temperatures
      (Tm) and enhanced heat capacities (Cp) in differential scanning calorimetric
      analysis. The results suggest that methylglyoxal significantly altered the
      structure of the nuclear histone H2A by non enzymatic glycation reaction. The
      conformational changes in histone H2A may influence the chromatin integrity which
      may have implications in various pathological conditions. 

PMID- 24879923
TI  - Large-scale evaluation of ANTs and FreeSurfer cortical thickness measurements.
AB  - Many studies of the human brain have explored the relationship between cortical
      thickness and cognition, phenotype, or disease. Due to the subjectivity and time
      requirements in manual measurement of cortical thickness, scientists have relied
      on robust software tools for automation which facilitate the testing and
      refinement of neuroscientific hypotheses. The most widely used tool for cortical
      thickness studies is the publicly available, surface-based FreeSurfer package.
      Critical to the adoption of such tools is a demonstration of their
      reproducibility, validity, and the documentation of specific implementations that
      are robust across large, diverse imaging datasets. To this end, we have developed
      the automated, volume-based Advanced Normalization Tools (ANTs) cortical
      thickness pipeline comprising well-vetted components such as SyGN (multivariate
      template construction), SyN (image registration), N4 (bias correction), Atropos
      (n-tissue segmentation), and DiReCT (cortical thickness estimation). In this
      work, we have conducted the largest evaluation of automated cortical thickness
      measures in publicly available data, comparing FreeSurfer and ANTs measures
      computed on 1205 images from four open data sets (IXI, MMRR, NKI, and OASIS),
      with parcellation based on the recently proposed Desikan-Killiany-Tourville (DKT)
      cortical labeling protocol. We found good scan-rescan repeatability with both
      FreeSurfer and ANTs measures. Given that such assessments of precision do not
      necessarily reflect accuracy or an ability to make statistical inferences, we
      further tested the neurobiological validity of these approaches by evaluating
      thickness-based prediction of age and gender. ANTs is shown to have a higher
      predictive performance than FreeSurfer for both of these measures. In promotion
      of open science, we make all of our scripts, data, and results publicly available
      which complements the use of open image data sets and the open source
      availability of the proposed ANTs cortical thickness pipeline. 

PMID- 24879925
TI  - Delayed diagnosis of Eosinophilic Fasciitis: a case report and review of the
      literature.
AB  - Eosinophilic fasciitis is an uncommon entity characterized by edema, skin
      thickening and hyperpigmentation of extremities. Laboratory findings are variable
      and may include hypergammaglobulemia, peripheral eosinophilia and elevated acute
      phase reactants. A full-thickness skin/fascia/muscle biopsy is the gold standart
      for diagnosis. Since EF is an uncommon disorder and the clinic presentation
      mimics scleroderma, it takes a long time to make definitive diagnosis. We present
      a case diagnosed two years after its onset and responded well to the treatment.
      We also include herein the results of our literature survey regarding delayed
      diagnosis of Eosinophilic Fasciitis. 

PMID- 24879924
TI  - Shrinkage prediction of seed-voxel brain connectivity using resting state fMRI.
AB  - Resting-state functional magnetic resonance imaging (rs-fMRI) is used to
      investigate synchronous activations in spatially distinct regions of the brain,
      which are thought to reflect functional systems supporting cognitive processes.
      Analyses are often performed using seed-based correlation analysis, allowing
      researchers to explore functional connectivity between data in a seed region and
      the rest of the brain. Using scan-rescan rs-fMRI data, we investigate how well
      the subject-specific seed-based correlation map from the second replication of
      the study can be predicted using data from the first replication. We show that
      one can dramatically improve prediction of subject-specific connectivity by
      borrowing strength from the group correlation map computed using all other
      subjects in the study. Even more surprisingly, we found that the group
      correlation map provided a better prediction of a subject's connectivity than the
      individual's own data. While further discussion and experimentation are required
      to understand how this can be used in practice, results indicate that shrinkage
      based methods that borrow strength from the population mean should play a role in
      rs-fMRI data analysis. 

PMID- 24879927
TI  - Differences in acute anorectic effects of long-acting GLP-1 receptor agonists in
      rats.
AB  - Long-acting glucagon-like peptide-1 receptor (GLP-1R) agonists have both glucose-
      and weight-lowering effects. The brain is poised to mediate both of these actions
      since GLP-1Rs are present in key areas known to control weight and glucose.
      Although some research has been performed on the effects of exendin-4 in the
      brain, little data exists on the central effects of liraglutide, a long-acting
      GLP-1R agonist with much closer structural homology to native GLP-1. In lean,
      Long-Evans rats, we found that direct intra-third cerebroventricular (i3vt)
      administration of 0.26 nmol liraglutide caused a 50% reduction in food intake.
      However, exendin-4 produced the same reduction in food intake with 10-fold
      greater potency (0.02 nmol). These data are supported by similar c-Fos
      immunoreactivity in the hypothalamic paraventricular nuclei by exendin-4 as
      compared to liraglutide despite differing doses. The anorectic effects of both
      drugs were blocked with i3vt pre-treatment of a GLP-1R competitive antagonist,
      exendin(9-39), indicating that both drugs required the GLP-1R for their effects.
      Exendin-4, and not liraglutide, caused hyperglycemia when given i3vt prior to an
      oral glucose tolerance test, although liraglutide did not lower glucose. Thus,
      these data show that GLP-1R agonists have differing anorectic potencies in the
      CNS, which may account for some of their clinical differences. Additionally, we
      show here that the glucose lowering properties of acute administration of GLP-1R
      agonists are not accounted for by their central effects.

PMID- 24879928
TI  - New metabolic activity of the nonsulfated sulfakinin Zopat-SK-1 in the insect fat
      body.
AB  - Insect sulfakinins are multifunctional neuropeptides homologous to vertebrate
      gastrin/cholecystokin (CCK) neuropeptide hormones. We investigated the action of
      the nonsulfated sulfakinin Zopat-SK-1 (pETSDDYGHLRFa) on the levels of chosen
      metabolites in the Zophobas atratus beetle fat body. Samples of fat body were
      collected 2h and 24h after hormone injection. The administration of 20pmol of
      Zopat-SK-1 to feeding larvae significantly increased concentrations of lipids and
      proteins and decreased the content of glycogen in fat body tissue in the 24h
      experimental group. In contrast, the only increase in total lipid concentration
      in prepupal fat bodies was observed 24h after Zopat-SK-1 treatment.
      Simultaneously, changes in the quality and quantity of free sugars in the
      hemolymph were measured. In larval hemolymph, a marked increase in free sugar
      concentration and a decrease in glucose content were observed 24h and 2h after
      Zopat-SK-1 application, respectively. No changes in the prepupal stage were
      observed. For the first time we show potent metabolic activity of sulfakinin in
      the fat body tissue of an insect. Our findings imply a physiological function of
      the nonsulfated form of sulfakinin in energy storage and release processes in fat
      body tissue of larvae and prepupae was indicated. We suggest a role for
      sulfakinin signaling in the regulation of energy metabolism in insect tissues. 

PMID- 24879926
TI  - Risk of lymphoma in patients with inflammatory bowel disease treated with
      azathioprine and 6-mercaptopurine: a meta-analysis.
AB  - BACKGROUND & AIMS: Thiopurine therapy for inflammatory bowel disease (IBD) has
      been associated with increased risk for lymphoma. We estimated the relative risk
      of lymphoma in patients with IBD exposed to thiopurines and compared relative
      risk values derived from population-based studies with those from referral center
      based studies. We investigated whether active use increased risk compared with
      past use, and whether sex, age, or duration of use affects risk of lymphoma.
      METHODS: We searched MEDLINE, EMBASE, and Cochrane databases, as well as
      conference abstracts and international publications, for the terms "6-MP and
      lymphoma," "6-mercaptopurine and lymphoma," "thiopurines and lymphoma,"
      "azathioprine and cancer and IBD," "azathioprine and malignancy and IBD,"
      "azathioprine and lymphoma," and "lymphoproliferative and thiopurines." Pooled
      standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were
      estimated. The deviance statistic from Poisson models was used to calculate
      heterogeneity. RESULTS: Eighteen studies (among 4383 citations) met our inclusion
      criteria. Overall, the SIR for lymphoma was 4.92 (95% CI, 3.10-7.78), ranging
      from 2.80 (95% CI, 1.82-4.32) in 8 population studies to 9.24 (95% CI, 4.69-18.2)
      in 10 referral studies. Population studies demonstrated an increased risk among
      current users (SIR = 5.71; 95% CI, 3.72-10.1) but not former users (SIR = 1.42;
      95% CI, 0.86-2.34). Level of risk became significant after 1 year of exposure.
      Men have a greater risk than women (relative risk = 1.98; P < .05); both sexes
      were at increased risk for lymphoma (SIR for men = 4.50; 95% CI = 3.71-5.40 and
      SIR for women = 2.29; 95% CI = 1.69-3.05). Patients younger than 30 years had the
      highest relative risk (SIR = 6.99; 95% CI, 2.99-16.4); younger men had the
      highest risk. The absolute risk was highest in patients older than 50 years
      (1:354 cases per patient-year, with a relative risk of 4.78). CONCLUSIONS:
      Compared with studies from referral centers, population-based studies of IBD
      patients show a lower but significantly increased risk of lymphoma among patients
      taking thiopurines. The increased risk does not appear to persist after
      discontinuation of therapy. Patients over 50 have the highest absolute risk of
      lymphoma per year on thiopurines, while men under 35 may also be a high risk
      group. More study is needed to precisely understand groups highest at risk. The
      risks of lymphoma and potential benefits of therapy should be considered for all
      patients with IBD.

PMID- 24879929
TI  - Effects of chlorate on the sulfation process of Trypanosoma cruzi
      glycoconjugates. Implication of parasite sulfates in cellular invasion.
AB  - Sulfation, a post-translational modification which plays a key role in various
      biological processes, is inhibited by competition with chlorate. In Trypanosoma
      cruzi, the agent of Chagas' disease, sulfated structures have been described as
      part of glycolipids and we have reported sulfated high-mannose type
      oligosaccharides in the C-T domain of the cruzipain (Cz) glycoprotein. However,
      sulfation pathways have not been described yet in this parasite. Herein, we
      studied the effect of chlorate treatment on T. cruzi with the aim to gain some
      knowledge about sulfation metabolism and the role of sulfated molecules in this
      parasite. In chlorate-treated epimastigotes, immunoblotting with anti-sulfates
      enriched Cz IgGs (AS-enriched IgGs) showed Cz undersulfation. Accordingly, a Cz
      mobility shift toward higher isoelectric points was observed in 2D-PAGE probed
      with anti-Cz antibodies. Ultrastructural membrane abnormalities and a significant
      decrease of dark lipid reservosomes were shown by electron microscopy and a
      significant decrease in sulfatide levels was confirmed by TLC/UV-MALDI-TOF-MS
      analysis. Altogether, these results suggest T. cruzi sulfation occurs via PAPS.
      Sulfated epitopes in trypomastigote and amastigote forms were evidenced using AS
      enriched IgGs by immunoblotting. Their presence on trypomastigotes surface was
      demonstrated by flow cytometry and IF with Cz/dCz specific antibodies.
      Interestingly, the percentage of infected cardiac HL-1 cells decreased 40% when
      using chlorate-treated trypomastigotes, suggesting sulfates are involved in the
      invasion process. The same effect was observed when cells were pre-incubated with
      dCz, dC-T or an anti-high mannose receptor (HMR) antibody, suggesting Cz sulfates
      and HMR are also involved in the infection process by T. cruzi. 

PMID- 24879930
TI  - Aflagellar epimastigote forms are found in axenic culture of Trypanosoma caninum.
AB  - Representatives of the genus Trypanosoma have been traditionally found in
      epimastigote, espheromastigote and trypomastigote flagellated forms in axenic
      cultures. Trypanosoma caninum is a trypanosomatid that has recently been reported
      infecting dogs in endemic areas of canine leishmaniasis in Brazil. It presents
      specific biological characteristics and it is found exclusively on healthy skin.
      Here, we describe the evolutive forms of this parasite showing not only the forms
      commonly found in culture, but also epimastigote forms with no free flagellum.
      The study was conducted using scanning and transmission electron microscopy and,
      we demonstrate that typical flagellated epimastigotes originate from forms
      without flagellum, although the latter may remain without differentiation in the
      culture. Two hypotheses are considered and discussed in this paper: (i) the
      aflagellated epimastigotes are a typical developmental forms of T. caninum and
      (ii) the emergence of these aflagellated forms could be resultant from a
      disturbed process during cell division caused by interfering specific proteins,
      which leads to inability to form and regulate the flagellum length. In any case,
      considering that T. caninum is a parasite that is still little studied, the
      information brought by our study adds data which may be useful to clarify aspects
      on the cell cycle of this intriguing parasite that has been found in different
      regions of Brazil. 

PMID- 24879931
TI  - Regulation of hypothalamic-pituitary-interrenal axis function in male smallmouth
      bass (Micropterus dolomieu) during parental care.
AB  - Male smallmouth bass (Micropterus dolomieu) provide sole parental care until
      offspring reach independence, a period of several weeks. During the early
      parental care period when males are guarding fresh eggs (MG-FE), cortisol
      responsiveness is attenuated; the response is re-established when males reach the
      end of the parental care period and are guarding free-swimming fry (MG-FSF). It
      was hypothesized that attenuation of the cortisol response in male smallmouth
      bass during early parental care reflected modulation of hypothalamic-pituitary
      interrenal (HPI) axis function. Male smallmouth bass were sampled at the
      beginning (MG-FE) and end of the parental care period (MG-FSF), before and/or 25
      min after exposure to a standardized stressor consisting of 3 min of air
      exposure. Repeated sampling of stressed fish for analysis of plasma cortisol and
      adrenocorticotropic hormone (ACTH) levels was carried out. Males significantly
      elevated both plasma cortisol and ACTH levels when guarding free-swimming fry but
      not during early parental care. Control and stressed fish were terminally sampled
      for tissue mRNA abundance of preoptic area (POA) and hypothalamic corticotropin
      releasing factor (CRF) as well as head kidney melanocortin 2 receptor (MC2R),
      steroidogenic acute regulatory protein (StAR) and cytochrome P450 side chain
      cleavage enzyme (P450scc). No significant differences in either hypothalamus CRF
      or head kidney P450scc mRNA abundance were found across parental care stages or
      in response to stress. However, POA CRF mRNA abundance and interrenal cell MC2R
      and StAR mRNA abundances failed to increase in response to stress in MG-FE. Thus,
      the attenuated cortisol response in males guarding fresh eggs may be explained by
      hypoactive HPI axis function in response to stress. The present is one of few
      studies, and the first teleost study, to address the mechanisms underlying
      resistance to stress during the reproductive/parental care period.

PMID- 24879932
TI  - Duane syndrome associated with features of the cat-eye syndrome and mosaicism for
      a supernumerary chromosome probably derived from number 22.
AB  - A 12-year-old boy with a supernumerary chromosome, probably derived from number
      22, had typical features of Duane syndrome with limitation of abduction and
      retraction of the globe upon adduction. Additionally, the patient had
      antimongoloid slant of the eyes, epicanthal folds, preauricular sinuses, cardiac
      malformations, skeletal malformations, and mental retardation suggestive of the
      cat-eye syndrome. The cat-eye syndrome has been often associated with a
      supernumerary chromosome derived from number 22. Our patient's karyotype was
      46,XY/47,XY, + mar, with the supernumerary chromosome probably derived from
      number 22. These findings supplement previous findings of chromosome 22
      abnormality associated with an ocular motility disorder.

PMID- 24879935
TI  - In vivo evaluation of an oral self-microemulsifying drug delivery system (SMEDDS)
      for leuprorelin.
AB  - The objective of this study was to develop a self-microemulsifying drug delivery
      system (SMEDDS) for the model peptide drug leuprorelin to prove a protective
      effect against luminal enzymatic metabolism. In order to incorporate leuprorelin
      into microemulsion droplets (o/w), the commercially available hydrophilic
      leuprolide acetate was modified by hydrophobic ion paring with sodium oleate. The
      obtained hydrophobic leuprolide oleate was dissolved in the SMEDDS formulation
      (30% (m/m) Cremophor EL, 30% (m/m) Capmul MCM, 10% (m/m) propylene glycol and 30%
      (m/m) Captex 355) in a concentration of 4 mg/g showing a mean droplet size of
      50.1 nm when dispersed in a concentration of 1% (m/v) in phosphate buffer pH 6.8.
      The microemulsion was able to shield leuprolide oleate from enzymatic degradation
      by trypsin and alpha-chymotrypsin, so that after 120 min 52.9% and 58.4%,
      respectively, of leuprolide oleate were still intact. Leuprolide acetate
      dissolved in an aqueous control solution was completely metabolized by trypsin
      within 60 min and by alpha-chymotrypsin within 5 min. Moreover, an in vivo study
      in rats showed a 17.2-fold improved oral bioavailability of leuprolide oleate
      SMEDDS compared to a leuprolide acetate control solution. This is the first time,
      to our knowledge, that hydrophobic ion pairing is utilized in order to
      incorporate a peptide drug in SMEDDS and evidence of a protective effect of oil
      in-water (o/w) microemulsion droplets against enzymatic degradation of a peptide
      drug was provided. According to these results, the system could be likely a novel
      platform technology to improve the oral bioavailability of peptide drugs.

PMID- 24879936
TI  - Oral transmucosal drug delivery--current status and future prospects.
AB  - Oral transmucosal drug delivery (OTDD) dosage forms have been available since the
      1980s. In contrast to the number of actives currently delivered locally to the
      oral cavity, the number delivered as buccal or sublingual formulations remains
      relatively low. This is surprising in view of the advantages associated with
      OTDD, compared with conventional oral drug delivery. This review examines a
      number of aspects related to OTDD including the anatomy of the oral cavity,
      models currently used to study OTDD, as well as commercially available
      formulations and emerging technologies. The limitations of current methodologies
      to study OTDD are considered as well as recent publications and new approaches
      which have advanced our understanding of this route of drug delivery. 

PMID- 24879938
TI  - Heat induced evaporative antisolvent nanoprecipitation (HIEAN) of itraconazole.
AB  - Itraconazole (ITR) is an antifungal drug with a limited bioavailability due to
      its poor aqueous solubility. In this study, ITR was used to investigate the
      impact of nanonisation and solid state change on drug's apparent solubility and
      dissolution. A bottom up approach to the production of amorphous ITR
      nanoparticles (NPs), composed of 100% drug, with a particle diameter below 250
      nm, using heat induced evaporative antisolvent nanoprecipitation (HIEAN) from
      acetone was developed. The NPs demonstrated improved solubility and dissolution
      in simulated gastro-intestinal conditions when compared to amorphous ITR
      microparticles. The incorporation of polyethylene glycol (PEG) or its
      methoxylated derivative (MPEG) as a stabiliser enabled the production of smaller
      NPs with narrower particle size distribution and enhanced apparent solubility.
      MPEG stabilised NPs gave the greatest ITR supersaturation levels (up to 11.6+/
      0.5 MUg/ml) in simulated gastric fluids. The stabilising polymer was in an
      amorphous state. Dynamic vapour sorption data indicated no solid state changes in
      NP samples with water vapour at 25  degrees C, while crystallisation was apparent
      at 50  degrees C. HIEAN proved to be an efficient method of production of
      amorphous ITR NPs, with or without addition of a polymeric stabiliser, with
      enhanced pharmaceutical properties.

PMID- 24879937
TI  - SN38 polymeric nanoparticles: in vitro cytotoxicity and in vivo antitumor
      efficacy in xenograft balb/c model with breast cancer versus irinotecan.
AB  - SN38 (7-ethyl-10-hydroxyl camptothecin), a potent metabolite of irinotecan, has
      been considered as an anticancer candidate. Its clinical development has been
      hampered due to its poor solubility. As a result, SN38 loaded poly lactic-co
      glycolic acid (PLGA) nanoparticles (NPs) was developed in current study to solve
      its poor water solubility problem while maintaining its cytotoxicity against
      cancer cells. PLGA NPs were prepared using modified emulsification-solvent
      evaporation technique and their characteristics were optimized by central
      composite experimental design in which average size, entrapment efficiency and
      drug loading were 170.5+/-11.87 nm, 77.35%+/-2.314 and 5.95%+/-0.087,
      respectively. Scanning electron microscopy and in vitro studies consisting of
      drug release and cytotoxicity in 4T1 breast cancer cells followed by in vivo
      biodistribution and blood cytotoxicity were carried out. Therapeutic efficacy of
      SN38-NPs was evaluated in xenograft balb/c animal with 4T1 breast cancer. The
      results demonstrated that the treatment with SN38-NPs was more efficacious in
      comparison with irinotecan. In conclusion, superior cytotoxic effect and improved
      in vivo antitumor efficacy of SN38-NPs versus irinotecan introduced SN38-NPs as a
      promising candidate for cancer treatment investigation.

PMID- 24879939
TI  - A novel approach to enhance the mucoadhesion of lipid drug nanocarriers for
      improved drug delivery to the buccal mucosa.
AB  - Targeted drug delivery to the buccal mucosa offers distinct advantages over oral
      delivery to the gastrointestinal tract including by-passing hepatic first-pass
      metabolism. However, the buccal route is often limited by low bioavailability,
      low drug loading and reduced residence time due to salivary excretion and
      clearance. To overcome these limitations, a novel mucoadhesive formulation based
      on liquid crystalline nanoparticles was designed. Utilising a pH induced in situ
      transition from a stable vesicle formulation to dispersed inverse hexagonal phase
      nanoparticles (hexosomes) enhanced adsorption onto the mucosal surface was
      enabled. Firstly, the phase behaviour of the amphiphilic lipid phytantriol (PHY)
      and oleic acid (OA) was assessed from pH 2-9 using small-angle X-ray scattering
      (SAXS) and cryo-transmission electron microscopy (cryo-TEM) to determine the
      appropriate composition for the vesicle to hexosome transition. The colloidal
      stability of the formulation was determined using turbidity studies. Dispersions
      comprising 30% w/w OA in PHY were able to form stable vesicles at pH 8 and
      transition to hexosomes when exposed to pH<7 (as encountered on the buccal
      mucosal surface). Subsequent ex vivo studies utilising excised porcine buccal
      tissue indicated significant retention of the in situ-formed PHY/OA hexosomes
      when compared to control DOPC vesicles (p<0.005), confirmed independently using
      confocal fluorescence microscopy, radioactive scintillation counting and HPLC
      analysis for incorporated drug. Thus, a novel approach providing a stable vesicle
      formulation, with in situ transformation to mucoadhesive hexosomes has been
      identified with the potential to enhance drug delivery to mucosal surfaces. 

PMID- 24879940
TI  - Characterization and function analysis of an anti-lipopolysaccharide factor (ALF)
      from the Chinese shrimp Fenneropenaeus chinensis.
AB  - Anti-lipopolysaccharide factor (ALF) is one of the widely-studied antimicrobial
      peptides (AMPs) with broad-spectrum antibacterial activity and antiviral
      property. Previous studies show the existence of multiform of ALFs in crustacean
      which are important for immunity of the animals. In the present study, we
      characterized one isoform of ALF from the Chinese shrimp Fenneropenaeus chinensis
      (FcALF2). Tissue distribution analysis revealed that FcALF2 showed the highest
      expression level in the lymphoid organ (Oka) of the shrimp. The expression level
      of FcALF2 in shrimp was significantly up-regulated when they were injected with
      Micrococcus lysodeikticus and Vibrio anguillarum. A peptide corresponding to the
      LPS-binding domain of FcALF2 (FcALF2-LBD) was synthesized to analyze its
      antimicrobial activities. Data demonstrated that FcALF2-LBD possessed strong
      antibacterial activity against Gram-positive bacteria Micrococcus luteus and
      M.lysodeikticus with MIC ranges of 2-4 MUM and 1-2 MUM respectively and
      significant inhibition activity against white spot syndrome virus (WSSV). The
      antibacterial activities of the sequence modified peptides (FcALF2-LBDb, FcALF2
      LBDv) were apparently enhanced and broadened after the amount of basic amino
      acids was increased in the synthetic LPS-binding domain. These data provide more
      insights into understanding the function of LPS-binding domain of ALF and the
      role of ALF in shrimp immunity.

PMID- 24879941
TI  - A handcrafted tissue microarray for a matrix arrangement of tissue samples.
AB  - INTRODUCTION: Tissue microarray (TMA) was first designed to enable more efficient
      immunohistochemical screening of antibodies and tissues. However, due to the high
      cost of commercial TMA builder instrument, such method is not affordable for many
      pathology laboratories. Then, methodological adaptations have been proposed in
      order to reduce TMA-associated cost. METHODS: A manual leather puncher with an
      inner diameter of 2mm was used to collect a tissue sample from the donor paraffin
      block. The conventional TMA method was adopted as a control group. RESULTS: Empty
      paraffin recipient blocks were prepared and a standard 2-mm crochet needle was
      used to create 24 equidistant holes in the recipient block. Tissue cores obtained
      from the donor blocks were transferred to the holes in the recipient blocks and
      routine histopathological techniques were then performed. DISCUSSION: In this
      study we proposed a new approach to produce TMA recipient blocks as an
      alternative to the conventional TMA.

PMID- 24879943
TI  - Prognostic value of antinuclear antibodies in juvenile idiopathic arthritis and
      anterior uveitis. Results from a systematic literature review.
AB  - AIMS: To analyze the prognostic role of antinuclear antibodies (ANA) for the
      onset of uveitis in the context of juvenile idiopathic arthritis (JIA), its
      correlation with uveitis course and severity and its prognostic role for the
      development of arthritis in children with uveitis. METHODS: We conducted a
      systematic review analysis of the literature on the prognostic value of ANA on
      JIA associated uveitis and its complications. We included series published
      between January 1990 and December 2011 reporting the prognostic value of ANA
      positivity on uveitis in consecutive patients diagnosed with JIA. RESULTS: We
      identified 246 studies from our search, of which 25 were selected for detailed
      analysis and only 9 fulfilled the inclusion criteria. Some authors have mentioned
      that uveitis could preceed arthritis and that ANA positivity might represent a
      predictive factor for subsequent joint involvement. A chronic course and
      insidious onset of uveitis are predictors for an association with JIA. Although
      recognized as a possible predictor of uveitis development, presence of positive
      ANA does not represent a predictor of severity. CONCLUSIONS: The presence of ANAs
      seems to be a risk factor for ocular involvement in patients with JIA. These
      autoantibodies, however, did not have any correlation with the recurrence of
      either idiopathic anterior uveitis or JIA-related uveitis and cannot be used as a
      marker to predict the clinical course of ocular inflammation. Any analysis of the
      literature is subjected to the limitations of each of the studies under
      evaluation. A large, prospective population-based study of JIA patients would be
      certainly ideal.

PMID- 24879942
TI  - Translational PK/PD modeling for cardiovascular safety assessment of drug
      candidates: Methods and examples in drug development.
AB  - INTRODUCTION: Cardiovascular toxicity is a significant cause of candidate failure
      in drug development. Pharmacokinetic/pharmacodynamic (PK/PD) modeling may reduce
      attrition by improving the understanding of the relationship between drug
      exposure and changes in cardiovascular endpoints. Diverse examples are discussed
      that elucidate how modeling can facilitate the interpretation of cardiovascular
      safety data in animals and enable quantitative translation of preclinical
      findings to man. METHODS: Twelve compounds under development in diverse
      therapeutic areas were tested in cardiovascular safety studies in the telemetered
      beagle dog and cynomolgus monkey. Drug-induced changes observed in different
      cardiovascular endpoints (QRS complex and QTc interval of the ECG, heart rate,
      blood pressure, and myocardial contractility) were described by means of PK/PD
      modeling. A range of direct and indirect effect models were employed to
      characterize the plasma concentration-cardiovascular effect relationship for each
      compound. RESULTS: For every drug candidate the proposed PK/PD models
      appropriately described the cardiovascular effects observed in dog and monkey.
      Two of the compounds subsequently reached clinical development and cardiovascular
      data were generated in first-in-human clinical trials. For one drug candidate, a
      threshold model was used to describe QTc prolongation in the monkey and man.
      Blood pressure changes induced by the second compound were linked to plasma
      exposure in dog and human via an indirect response model. In both cases it was
      found that translational modeling accurately predicted the human response
      observed during clinical development. DISCUSSION: In this article, a range of
      PK/PD models are discussed that successfully described cardiovascular safety
      findings in the preclinical setting. Where clinical data were available, it was
      found that translational modeling enabled the accurate prediction of outcomes in
      man and facilitated the description of the therapeutic index. PK/PD modeling is
      thus demonstrated as a powerful tool to aid in the quantitative cardiovascular
      safety assessment of drug candidates and the optimization of early clinical study
      protocols.

PMID- 24879944
TI  - A longitudinal comparison of spectral-domain optical coherence tomography and
      fundus autofluorescence in geographic atrophy.
AB  - PURPOSE: To identify reliable criteria based on spectral-domain optical coherence
      tomography (SD OCT) to monitor disease progression in geographic atrophy
      attributable to age-related macular degeneration (AMD) compared with lesion size
      determination based on fundus autofluorescence (FAF). DESIGN: Prospective
      longitudinal observational study. METHODS: setting: Institutional. study
      population: A total of 48 eyes in 24 patients with geographic atrophy.
      observation procedures: Eyes with geographic atrophy were included and examined
      at baseline and at months 3, 6, 9, and 12. At each study visit best-corrected
      visual acuity (BCVA), FAF, and SD OCT imaging were performed. FAF images were
      analyzed using the region overlay device. Planimetric measurements in SD OCT,
      including alterations or loss of outer retinal layers and the RPE, as well as
      choroidal signal enhancement, were performed with the OCT Toolkit. main outcome
      measures: Areas of interest in patients with geographic atrophy measured from
      baseline to month 12 by SD OCT compared with the area of atrophy measured by FAF.
      RESULTS: Geographic atrophy lesion size increased from 8.88 mm2 to 11.22 mm2
      based on quantitative FAF evaluation. Linear regression analysis demonstrated
      that results similar to FAF planimetry for determining lesion progression can be
      obtained by measuring the areas of outer plexiform layer thinning (adjusted R(2)
      = 0.93), external limiting membrane loss (adjusted R(2) = 0.89), or choroidal
      signal enhancement (R(2) = 0.93) by SD OCT. CONCLUSIONS: SD OCT allows
      morphologic markers of disease progression to be identified in geographic atrophy
      and may improve understanding of the pathophysiology of atrophic AMD.

PMID- 24879945
TI  - Endothelial cell changes as an indicator for upcoming allograft rejection
      following descemet membrane endothelial keratoplasty.
AB  - PURPOSE: To report early, specific changes in donor endothelial cell morphology
      as a predictor of an upcoming allograft rejection after Descemet membrane
      endothelial keratoplasty (DMEK). DESIGN: Retrospective, observational case
      series. METHODS: Out of a cohort of 500 eyes that underwent DMEK at a tertiary
      referral center, 7 eyes developed typical clinical signs of an allograft
      rejection. Specular microscopy images before, during, and after the rejection
      episode were analyzed and compared with a case-control group of 49 asymptomatic
      DMEK eyes that matched baseline characteristics of the rejection group.
      Endothelial cell morphology was evaluated by subjective scoring (range 1-5) in a
      masked fashion as well as by an objective comparison of endothelial cell density,
      cell size, coefficient of variation, and hexagonality in rejection vs control
      eyes. RESULTS: Subjective scores (median) were higher before and after rejection
      (2.5 and 5, respectively) than in the DMEK control group (2.0 and 2.5,
      respectively) at comparable time points (P = .0230 and P = .0005, respectively).
      Endothelial cell density also differed before (P = .0106) and after rejection (P
      = .0240), while hexagonality differed before (P = .0499) but not after rejection
      (P = .1767). CONCLUSION: Our study suggests that allograft rejection may not be
      an acute event, but rather a slow-onset immune response. Early, specific changes
      in endothelial cell morphology were found to "announce" an upcoming allograft
      rejection. If so, monitoring donor endothelium after DMEK or other forms of
      keratoplasty may be used to anticipate a rejection episode and/or to prevent an
      allograft rejection from clinically manifesting itself.

PMID- 24879947
TI  - Optical coherence tomography retinal thickness and volume measurements in X
      linked retinoschisis.
AB  - PURPOSE: To analyze retinal thickness and volume measurements of X-linked
      retinoschisis patients by spectral-domain optical coherence tomography (SD OCT)
      and correlate these findings with visual acuity and patient age. DESIGN:
      Retrospective comparative case series. METHODS: Sixty-three eyes of 33 male
      patients with X-linked retinoschisis were gleaned from a SD OCT database at the
      University of Illinois at Chicago. Forty-one eyes of 21 patients with low
      refractive error, no visual impairment, and no known retinal disease served as
      age-similar controls. The mean age of the retinoschisis patients was 26.4 years.
      The mean age of patient controls was 30.0 years. Full-thickness, inner and outer
      retina thickness, and volume measurements were determined by SD OCT. RESULTS:
      Foveal schisis was observed in 81% of retinoschisis patients. Patients with
      foveal schisis tended to be younger than patients lacking foveal schisis. Inner
      and outer foveal thickness and volume measurements were increased in
      retinoschisis patients compared to controls. Outer retinal perifoveal and
      parafoveal thicknesses and volumes were consistently increased in retinoschisis
      patients relative to controls. In contrast, inner retinal perifoveal and
      parafoveal thickness and volume measurements were decreased in retinoschisis
      patients compared to controls. Worse visual acuity correlated with thinning of
      the temporal perifoveal inner retina and thickening of the inner fovea. Full
      thickness measurements and inner retina and outer retina thickness and volume
      measurements tended to decrease with patient age. CONCLUSION: Increased inner
      retinal foveal thickness and decreased perifoveal inner retinal thickness
      correlates with worse visual acuity and overall retinal thickness decreases with
      age in X-linked retinoschisis.

PMID- 24879946
TI  - The association of blood pressure and primary open-angle glaucoma: a meta
      analysis.
AB  - PURPOSE: To conduct a systematic review and meta-analysis of the association
      between blood pressure levels and hypertension with primary open-angle glaucoma
      and intraocular pressure endpoints. DESIGN: Systematic review with quantitative
      meta-analysis. METHODS: Studies were identified by searching the PubMed and
      EMBASE databases. Inverse-variance weighted random-effects models were used to
      summarize relative risks. Subgroup analyses and meta-regression were used to
      explore potential sources of heterogeneity across studies. RESULTS: Sixty
      observational studies were included. The pooled relative risk for primary open
      angle glaucoma comparing patients with hypertension to those without hypertension
      was 1.16 (95% CI = 1.05-1.28), with modest heterogeneity across studies (I(2)
      34.5%). Virtually all studies reported a positive association between blood
      pressure and intraocular pressure (IOP). The pooled average increase in IOP
      associated with a 10 mm Hg increase in systolic blood pressure was 0.26 mm Hg
      (95% CI 0.23-0.28, I(2) 30.7%), and the average increase associated with a 5 mm
      Hg increase in diastolic blood pressure was 0.17 mm Hg (95% CI 0.11-0.23, I(2)
      90.5%). CONCLUSIONS: In this meta-analysis, hypertension was associated with
      increased intraocular pressure. The association between hypertension and primary
      open-angle glaucoma was stronger in cross-sectional compared with case-control
      and longitudinal studies. Our findings support a role of increased blood pressure
      in elevated intraocular pressure and possibly in the development of glaucoma.

PMID- 24879948
TI  - Suppression of intraocular vascular endothelial growth factor during aflibercept
      treatment of age-related macular degeneration.
AB  - PURPOSE: To determine the duration of suppression of aqueous humor concentrations
      of vascular endothelial growth factor (VEGF) in eyes with neovascular age-related
      macular degeneration (AMD) treated with aflibercept. DESIGN: Nonrandomized
      prospective clinical study. METHODS: Twenty-seven eyes of 27 neovascular AMD
      patients receiving intravitreal aflibercept injections on a pro re nata regimen
      driven by spectral-domain optical coherence tomography (SD OCT) were included in
      this study. A total of 132 aqueous humor specimens were collected before
      intravitreal aflibercept injections and their VEGF-A concentrations assayed by
      multiplex bead analysis. RESULTS: Mean aqueous humor VEGF concentrations before
      treatment initiation were 90.6 +/- 37.1 pg/mL (range 23.4-190.3 pg/mL).
      Intravitreal injection of aflibercept suppressed the aqueous VEGF concentrations
      to below the lower limit of quantification (<4 pg/mL) in all patients. The mean
      duration of VEGF suppression below the lower limit of quantification was >71 +/-
      18 days. The earliest time after injection at which the VEGF concentration
      recovered to above the lower limit of quantification was 55 days in 1 patient and
      >56 days, the recommended aflibercept treatment interval, in 20 patients. The
      aqueous VEGF recovery status of 6 patients was uncertain after 56 days.
      CONCLUSIONS: On average, VEGF concentrations in the aqueous humor were suppressed
      below the lower limit of quantification after intravitreal aflibercept injections
      for about 10 weeks. This aqueous suppression time suggests durable VEGF
      inhibition for most patients dosed with aflibercept every 8 weeks.

PMID- 24879950
TI  - SCN5A-related dilated cardiomyopathy: what do we know?

PMID- 24879949
TI  - Lipids, lipid genes, and incident age-related macular degeneration: the three
      continent age-related macular degeneration consortium.
AB  - PURPOSE: To describe associations of serum lipid levels and lipid pathway genes
      to the incidence of age-related macular degeneration (AMD). DESIGN: Meta
      analysis. METHODS: setting: Three population-based cohorts. population: A total
      of 6950 participants from the Beaver Dam Eye Study (BDES), Blue Mountains Eye
      Study (BMES), and Rotterdam Study (RS). observation procedures: Participants were
      followed over 20 years and examined at 5-year intervals. Hazard ratios associated
      with lipid levels per standard deviation above the mean or associated with each
      additional risk allele for each lipid pathway gene were calculated using random
      effects inverse-weighted meta-analysis models, adjusting for known AMD risk
      factors. main outcome measures: Incidence of AMD. RESULTS: The average 5-year
      incidences of early AMD were 8.1%, 15.1%, and 13.0% in the BDES, BMES, and RS,
      respectively. Substantial heterogeneity in the effect of cholesterol and lipid
      pathway genes on the incidence and progression of AMD was evident when the data
      from the 3 studies were combined in meta-analysis. After correction for multiple
      comparisons, we did not find a statistically significant association between any
      of the cholesterol measures, statin use, or serum lipid genes and any of the AMD
      outcomes in the meta-analysis. CONCLUSION: In a meta-analysis, there were no
      associations of cholesterol measures, history of statin use, or lipid pathway
      genes to the incidence and progression of AMD. These findings add to
      inconsistencies in earlier reports from our studies and others showing weak
      associations, no associations, or inverse associations of high-density
      lipoprotein cholesterol and total cholesterol with AMD.

PMID- 24879951
TI  - Reply to the editor--Left atrium, vagal nerve, and esophagus: a complex system in
      atrial fibrillation.

PMID- 24879952
TI  - Left atrium, vagal nerve, and esophagus: a neighborhood with close relations.

PMID- 24879954
TI  - Montelukast rescues primary neurons against Abeta1-42-induced toxicity through
      inhibiting CysLT1R-mediated NF-kappaB signaling.
AB  - Amyloid-beta peptide (Abeta), which can invoke a cascade of inflammatory
      responses, is considered to play a causal role in the development and progress of
      Alzheimer's disease (AD). Montelukast, known as a cysteinyl leukotriene receptor
      1 (CysLT1R) antagonist, is currently used for treatment of inflammatory diseases
      such as asthma. We have previously reported that CysLT1R activation is involved
      in Abeta generation. In this study, we investigated rescuing effect of CysLT1R
      antagonist montelukast on Abeta1-42-induced neurotoxicity in primary neurons. Our
      data showed that Abeta1-42 elicited a marked increase of CysLT1R expression in
      primary mouse neurons. This increment of CysLT1R expression was accompanied by
      increases of inflammatory factors such as NF-kappaB p65, tumor necrosis factor
      alpha (TNFalpha) and interleukin-1beta (IL-1beta) as well as pro-apoptotic
      protein Caspase-3 activation and anti-apoptosis protein Bcl-2 reduction. Abeta1
      42-mediated increase of CysLT1R expression was associated with Abeta1-42-induced
      cytotoxicity as measured by MTT reduction assay and lactate dehydrogenase (LDH)
      release assay. This observation was confirmed with treatment of montelukast, a
      selective CysLT1R antagonist, which had significant effect on Abeta1-42-induced
      cytotoxicity. Moreover, blockade of CysLT1R with montelukast reversed Abeta1-42
      mediated increase of CysLT1R expression, and concomitant changes of the pro
      inflammatory factors and the apoptosis-related proteins. The results demonstrate
      that montelukast rescued neurons against Abeta1-42-induced neurotoxicity,
      neuroinflammation and apoptosis by down-regulating CysLT1R-mediated NF-kappaB
      signaling, suggesting that CysLT1R may be a potential target for AD, and its
      antagonist may have beneficial effects for treatment of AD. 

PMID- 24879953
TI  - Oestradiol and progesterone differentially alter cytoskeletal protein expression
      and flame cell morphology in Taenia crassiceps.
AB  - We examined the effects of oestradiol (E2) and progesterone (P4) on cytoskeletal
      protein expression in the helminth Taenia crassiceps - specifically actin,
      tubulin and myosin. These proteins assemble into flame cells, which constitute
      the parasite excretory system. Total protein extracts were obtained from E2- and
      P4-treated T. crassiceps cysticerci and untreated controls, and analysed by one-
      and two-dimensional protein electrophoresis, flow cytometry, immunofluorescence
      and videomicroscopy. Exposure of T. crassiceps cysticerci to E2 and P4 induced
      differential protein expression patterns compared with untreated controls.
      Changes in actin, tubulin and myosin expression were confirmed by flow cytometry
      of parasite cells and immunofluorescence. In addition, parasite morphology was
      altered in response to E2 and P4 versus controls. Flame cells were primarily
      affected at the level of the ciliary tuft, in association with the changes in
      actin, tubulin and myosin. We conclude that oestradiol and progesterone act
      directly on T. crassiceps cysticerci, altering actin, tubulin and myosin
      expression and thus affecting the assembly and function of flame cells. Our
      results increase our understanding of several aspects of the molecular crosstalk
      between host and parasite, which might be useful in designing anthelmintic drugs
      that exclusively impair parasitic proteins which mediate cell signaling and
      pathogenic reproduction and establishment. 

PMID- 24879955
TI  - Overacting oblique muscles in exotropia: a mechanical explanation.
AB  - Patients with exotropia often show apparent overaction of the inferior and
      superior oblique muscles. Are the oblique muscles contracted, are they truly
      overacting overacting, or does the eye flip up or down in adduction from the
      leash effect of a contracted lateral rectus muscle? Theoretically, if the
      mechanical limits of ocular rotations were circular or elliptical, rather than
      square or rectangular, we would expect a patient with exotropia to develop a
      vertical deviation in extreme gaze into the oblique quadrants, for the abducting
      eye would reach the mechanical limit, while the adducting eye would still be free
      to move up or down, giving the appearance of both inferior and superior oblique
      overaction. The circular or elliptical limits of ocular rotations were documented
      with tracings from slow-motion video recordings. Also, reduction of pseudo
      overation of the obliques in both eyes following unilateral surgery for exotropia
      was observed in three patients. The strabismus surgeon should be aware of this
      possible mechanism for pseudo-overaction of the obliques and should avoid muscle
      surgery in this clinical setting.

PMID- 24879959
TI  - Biological activity of Ganoderma lucidum basidiocarps cultivated on alternative
      and commercial substrate.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Ganoderma lucidum (W. Curt.:Fr.) P. Karst. has
      been used for several thousand years in traditional medicine of the Far East for
      the treatment of a various diseases including: cancer, immunological disorders,
      hepatitis, arthritis, nephritis, bronchitis, asthma etc. Ganoderma species are
      natural sources of various antimicrobial, antioxidant and antitumor active
      compounds which can be alternative to commercial antibiotics, antimycotics,
      antioxidants and cytostatics. As the amount of wild Ganoderma lucidum
      basidiocarps is not sufficient, the aim of this study was to compare the
      bioactivity of basidiaocarps obtained on alternative substrate (wheat straw) with
      commercially cultivated ones. MATERIALS AND METHODS: Antimicrobial potential of
      the tested Ganoderma lucidum extracts was studied by disc-diffusion and
      microdilution method. Cytotoxic effect of tested extracts on two cancer cell
      lines was determined by microculture tetrazolium test. DPPH scavenging ability,
      total phenols and flavonoids content were measured in order to determine the
      antioxidative potential of Ganoderma lucidum extracts. RESULTS: Ganoderma lucidum
      BEOFB 434 extract was the most effective antibacterial agent, while commercial
      strain was the weakest. DPPH. scavenging activity of extracts of basidiocarps
      from alternative substrate was also significantly higher than that of
      commercially obtained basidiocarps. The extracts of Ganoderma lucidum BEOFB 431
      exhibited the strongest cytotoxic activity significantly higher than those in
      commercial strain. CONCLUSION: The study showed that fruiting bodies produced on
      one of the most accessible and cheapest crop residue, wheat straw, are better
      antimicrobial, antioxidant and cytotoxic agents than those obtained on
      conventional substrate, oak sawdust.

PMID- 24879958
TI  - The effects of the standardized herbal formula PM014 on pulmonary inflammation
      and airway responsiveness in a murine model of cockroach allergen-induced asthma.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: PM014 is a modified form of the Chung-Sang-Bo-Ha
      Tang (CSBHT) herbal formula that has been used to treat chronic pulmonary
      diseases in Korea for centuries. Previously, we developed a formulation of PM014
      based on a series of in vitro and in vivo screening efforts that comprises seven
      herbal extracts. The PM014 formula includes the root of Rehmannia glutinosa, the
      cortex of Paeonia suffruticosa, the fruit of Schizandra chinensis, the root of
      Asparagus cochinchinensis, seeds of Prunus armeniaca, the root of Scutellaria
      baicalensis and the root of Stemona sessilifolia. Asthma is a chronic
      inflammatory disease of the lungs that is characterized by wheezing, bronchial
      contraction, and chest tightness. In addition, the airway becomes hypersensitive
      and narrows through an inflammatory reaction mediated by Th2 cells. The present
      study was conducted to evaluate the ability of PM014 to prevent allergic airway
      inflammation and to attenuate airway responses in a cockroach allergen-induced
      mouse model. MATERIALS AND METHODS: Mice sensitized to and challenged with
      cockroach allergen were treated with oral administration of PM014. Airway
      resistance was determined by whole body plethysmography. In addition, Th2
      cytokines and immune cell profiles of bronchoalveolar lavage (BAL) fluid and
      inflammatory mediators in serum were analyzed by ELISA. A series of histological
      examinations were also conducted to demonstrate the effects of PM014 on airway
      remodeling, goblet cell hyperplasia and inflammatory responses in the lung.
      RESULTS: PM014 significantly inhibited the number of total cells, eosinophils,
      neutrophils, macrophages and lymphocytes in the BAL fluid of mice that were
      challenged with cockroach allergen. In addition, PM014 reduced the levels of Th2
      cytokines (IL-4, IL-5 and IL-13) in the BAL fluid and inflammatory mediators such
      as IgE in the serum, as measured by enzyme-linked immunosorbent assay (ELISA).
      Histopathological analysis also showed that PM014 substantially inhibited
      eosinophil infiltration into the airway, goblet cell hyperplasia and smooth
      muscle hypertrophy. CONCLUSIONS: In this study, our results indicate that PM014
      has significant effects on allergic airway inflammation upon exposure to
      cockroach allergen in a mouse model. According to these outcomes, PM014 may have
      therapeutic potential as a treatment for allergic asthma.

PMID- 24879961
TI  - The chondrocyte primary cilium.
AB  - The presence and role of primary, or non-motile, cilia on chondrocytes has
      confused cartilage researchers for decades. Initial explanations attributed a
      vestigial nature to chondrocyte cilia. Evidence is now emerging that supports the
      role of the chondrocyte primary cilium as a sensory organelle, in particular, in
      mechanotransduction and as a compartment for signaling pathways. Early electron
      microscopy images depicted bent cilia aligned with the extracellular matrix (ECM)
      in a manner that suggested a response to mechanical forces. Molecules known to be
      mechanotransducers in other cell types, including integrins and proteoglycans,
      are present on chondrocyte cilia. Further, chondrocytes which lack cilia fail to
      respond to mechanical forces in the same manner that chondrocytes with intact
      cilia respond. From a clinical perspective, chondrocytes from osteoarthritic (OA)
      cartilage have cilia with different characteristics than cilia found on
      chondrocytes from healthy cartilage. OBJECTIVE: This review examines the evidence
      supporting the function of chondrocyte cilia and briefly speculates on the
      involvement of intraflagellar transport (IFT) in the signaling pathway of
      mechanotransduction through the cilium. CONCLUSIONS: Emerging evidence suggests
      cilia may be a promising target for preventing and treating OA.

PMID- 24879962
TI  - Tophaceous Gout: a tragic course for a preventable disease.
AB  - A 66-year-old man, with a history of chronic tophaceous gout since the age of 30,
      presented with multiple tophi and significant deformity of all fingers that
      caused substantial function loss. Due to osteomyelitis refractory to
      antimicrobial therapy, he underwent disarticulation of several fingers. Finally,
      both his hands were amputated. 

PMID- 24879963
TI  - Construction of a novel inducible expression vector for Lactococcus lactis M4 and
      Lactobacillus plantarum Pa21.
AB  - A vector that drives the expression of the reporter gusA gene in both
      Lactobacillus plantarum and Lactococcus lactis was constructed in this study.
      This vector contained a newly characterized heat shock promoter (Phsp), amplified
      from an Enterococcus faecium plasmid, pAR6. Functionality and characterization of
      this promoter was initially performed by cloning Phsp into pNZ8008, a commercial
      lactococcal plasmid used for screening of putative promoters which utilizes gusA
      as a reporter. It was observed that Phsp was induced under heat, salinity and
      alkaline stresses or a combination of all three stresses. The newly characterized
      Phsp promoter was then used to construct a novel Lactobacillus vector, pAR1801
      and its ability to express the gusA under stress-induced conditions was
      reproducible in both Lb. plantarum Pa21 and L. lactis M4 hosts. 

PMID- 24879964
TI  - Conceptualizing the construct of participation in adults with disabilities.
AB  - Participation is a key indicator of health and well-being and a critical
      rehabilitation goal for individuals with disabilities. Despite the numerous
      participation measures that have been developed, there is still an absence of
      agreement on the definition, domains, and dimensions of this construct. The
      result is that instruments intending to measure the same construct may actually
      measure quite different aspects of daily life and therefore yield significantly
      different findings. A solid conceptual model is needed to provide consistent
      guidance for measurement selection and development. In this article we identify
      the relevant content areas of participation and propose a conceptual model for
      adults that is intended to apply across diagnoses, conditions, and settings. We
      classified participation into 3 main domains: work and education, household, and
      community. Subdomains are defined within each. The model was reviewed using a
      semistructured survey by 8 rehabilitation measurement experts. Their feedback
      regarding the relevance, clarity, and comprehensiveness of the model led to the
      creation of an alternative structure in which the 3 main domains were
      recategorized as productivity, social, and community. The proposed conceptual
      model provides a clear framework for practitioners and researchers to understand
      the concept of participation and to guide selection or development of measures. 

PMID- 24879965
TI  - Impact of resistance training in chronic obstructive pulmonary disease patients
      during periods of acute exacerbation.
AB  - OBJECTIVE: To evaluate the effects of whole-body resistance training on exercise
      capacity, health-related quality of life (HRQOL), and muscle strength in patients
      hospitalized for exacerbation of chronic obstructive pulmonary disease. DESIGN:
      Randomized controlled trial. SETTING: University hospital. PARTICIPANTS: Patients
      (N=46) were randomized to either a control group (CG) or training group (TG), and
      29 patients completed the study. INTERVENTION: Training consisted of weight
      lifting exercises for 6 muscle groups in the upper and lower limbs (2 sets of 8
      repetitions each), and the initial load was set at 80% of the 1-repetition
      maximum load. MAIN OUTCOME MEASURES: Patients were evaluated on the second day of
      hospitalization, at hospital discharge, and 30 days postdischarge. Patients were
      evaluated on the basis of the 6-minute walking distance (6MWD), HRQOL, muscle
      strength, systemic inflammatory markers, and level of physical activity in daily
      life (PADL). RESULTS: The CG showed a reduction in the strength of lower-limb
      muscles (P<.05) but not in the 6MWD (P>.05). In contrast, patients from the TG
      improved strength in the lower-limb muscles and 6MWD during and 30 days after
      hospitalization (P<.05). The TG also improved the impact domain in HRQOL after
      hospitalization. No improvement in PADL was observed in the TG. Finally, a
      reduction in the blood levels of inflammatory markers was observed only in the TG
      after hospitalization. CONCLUSIONS: Our results suggest that resistance training
      during hospitalization improves the 6MWD, HRQOL, and lower-limb muscle strength,
      without altering the levels of systemic inflammation. However, future research
      should explore this intervention in larger randomized trials.

PMID- 24879966
TI  - A hyper-ferritinemia syndrome evolving in recurrent macrophage activation
      syndrome, as an onset of amyopathic juvenile dermatomyositis: a challenging
      clinical case in light of the current diagnostic criteria.
AB  - Juvenile dermatomyositis is an immune-mediated inflammatory multi-system disease
      involving mainly striated muscles and skin. Typical dermatological features are
      fundamental to establish the diagnosis, especially whenever the myopathy is very
      mild or absent, as it occurs in the form called as amyopathic juvenile
      dermatomyositis. Sometimes, systemic rheumatic diseases can develop a
      hyperferritinemia syndrome characterized by hemophagocytosis, namely macrophage
      activation syndrome, which represents a severe and life-threatening complication.
      Here, we describe a complex clinical history characterized by a hyper
      ferritinemia syndrome after infectious mononucleosis, leading to recurrent
      episodes of macrophage activation syndrome. Finally, the late onset of several
      skin changes brought to a diagnosis of amyopathic juvenile dermatomyositis. 

PMID- 24879967
TI  - Neural responses from the wind-sensitive interneuron population in four cockroach
      species.
AB  - The wind-sensitive insect cercal sensory system is involved in important
      behaviors including predator detection and initiating terrestrial escape
      responses as well as flight maintenance. However, not all insects possessing a
      cercal system exhibit these behaviors. In cockroaches, wind evokes strong
      terrestrial escape responses in Periplaneta americana and Blattella germanica,
      but only weak escape responses in Blaberus craniifer and no escape responses in
      Gromphadorhina portentosa. Both P. americana and B. craniifer possesses pink
      flight muscles correlated with flight ability while B. germanica possesses white
      flight muscles that cannot support flight and G. portentosa lacks wings. These
      different behavioral combinations could correlate with differences in sensory
      processing of wind information by the cercal system. In this study, we focused on
      the wind-sensitive interneurons (WSIs) since they provide input to the
      premotor/motor neurons that influence terrestrial escape and flight behavior.
      Using extracellular recordings, we characterized the responses from the WSI
      population by generating stimulus-response (S-R) curves and examining spike
      firing rates. Using cluster analysis, we also examined the activity of individual
      units (four per species, though not necessarily homologous) comprising the
      population response in each species. Our main results were: (1) all four species
      possessed ascending WSIs in the abdominal connectives; (2) wind elicited the
      weakest WSI responses (lowest spike counts and spike rates) in G. portentosa; (3)
      wind elicited WSI responses in B. craniifer that were greater than P. americana
      or B. germanica; (4) the activity of four individual units comprising the WSI
      population response in each species was similar across species. 

PMID- 24879968
TI  - The chemical defense in larvae of the earwig Forficula auricularia.
AB  - Larvae of the European earwig, Forficula auricularia, possess a paired pygidial
      gland with yet unknown content and function. We used gas chromatography-mass
      spectrometry to analyze the larval secretions revealing the presence of 2-methyl
      1,4-benzoquinone, 2-ethyl-1,4-benzoquinone, n-tridecane and n-pentadecane. Based
      on our recent discovery that the morphologically-distinct abdominal glands of
      adult earwigs produce secretions with antibacterial, antifungal and nematicidal
      activity, we propose that the pygidial glands mediate chemical defenses in the
      larvae. We next considered whether the defensive functions of larval secretions
      include repellent activity against sympatric predators. Therefore, we tested the
      effects of larval secretions on foraging workers of the ant species Myrmica
      rubra, the actively hunting spiders Anyphaena accentuata and Philodromus aureolus
      and the net-hunting spider Pholcus phalangioides in laboratory feeding assays.
      The secretion is released in response to ant attacks, and discourages feeding in
      M. rubra, however, it does not discourage feeding in spiders. Our results suggest
      that earwigs use different glands during ontogenesis to produce secretions that
      play roles in chemical defense against predators such as ants. 

PMID- 24879969
TI  - Progeny of Osmia lignaria from distinct regions differ in developmental phenology
      and survival under a common thermal regime.
AB  - Many insects, including some bees, have extensive subcontinental distributions
      that can differ in climatic conditions. Within and beyond these distributions,
      humans intentionally transport beneficial insects, including bees, to non-natal
      geographic locations. Insects also are experiencing unprecedented climatic change
      in their resident localities. For solitary bees, we know very little about the
      adaptive plasticity and geographic variation in developmental physiology that
      accommodates the different climates experienced within distributional ranges.
      Osmia lignaria Say (Hymenoptera: Megachilidae) is a widely distributed North
      American spring-emerging bee being developed as a managed pollinator for tree
      fruit crops, including almonds. We examined the development and survival of O.
      lignaria progeny that were descended from populations sourced from southern
      California, western Washington, and northern Utah, and then were reared together
      under an hourly and weekly temperature regime simulating those of a California
      almond-growing region. We found that developmental physiologies of Washington and
      Utah progeny were generally similar. However, California progeny developed
      slower, were more metabolically active, and survived better under California
      conditions than did populations native to regions at higher latitudes. Regardless
      of geographic origin, cocooned adults managed under prescribed thermal regimes
      emerged faster and lived longer after wintering. Progeny of parents from
      different regions exhibited some acclimatory plasticity in developmental
      phenologies to a novel climatic regime, but overall their responses reflected
      their geographic origins. This outcome is consistent with their developmental
      phenologies being largely heritable adaptations to regional climates. 

PMID- 24879970
TI  - Health assessment of gasoline and fuel oxygenate vapors: neurotoxicity
      evaluation.
AB  - Sprague-Dawley rats were exposed via inhalation to vapor condensates of either
      gasoline or gasoline combined with various fuel oxygenates to assess potential
      neurotoxicity of evaporative emissions. Test articles included vapor condensates
      prepared from "baseline gasoline" (BGVC), or gasoline combined with methyl
      tertiary butyl ether (G/MTBE), ethyl t-butyl ether (G/ETBE), t-amyl methyl ether
      (G/TAME), diisopropyl ether (G/DIPE), ethanol (G/EtOH), or t-butyl alcohol
      (G/TBA). Target concentrations were 0, 2000, 10,000 or 20,000mg/mg(3) and
      exposures were for 6h/day, 5days/week for 13weeks. The functional observation
      battery (FOB) with the addition of motor activity (MA) testing, hematoxylin and
      eosin staining of brain tissue sections, and brain regional analysis of glial
      fibrillary acidic protein (GFAP) were used to assess behavioral changes,
      traditional neuropathology and astrogliosis, respectively. FOB and MA data for
      all agents, except G/TBA, were negative. G/TBA behavioral effects resolved during
      recovery. Neuropathology was negative for all groups. Analyses of GFAP revealed
      increases in multiplebrain regions largely limited to males of the G/EtOH group,
      findings indicative of minor gliosis, most significantly in the cerebellum. Small
      changes (both increases and decreases) in GFAP were observed for other test
      agents but effects were not consistent across sex, brain region or exposure
      concentration.

PMID- 24879972
TI  - Comparing the inferior colliculus of young and old gerbils (Meriones
      unguiculatus) with an emphasis on GABA.
AB  - Indicators of an age-dependent down-regulation of GABA (gamma amino butyric acid)
      have been well-documented in the inferior colliculus (IC) of several rat strains.
      In the present study, we performed a quantitative light microscopic analysis of
      GABA-immunostained IC sections to characterize the effect of age on the cross
      sectional area of the IC, the number and density of GABAergic cells and the
      expression of GABA in gerbils. Compared to young gerbils, a significant shrinkage
      of the IC but no loss of GABAergic cells was found resulting in an increased
      density of GABAergic cells in old gerbils. The expression of GABA in neurons and
      the neuropil of the IC did not differ between young and old gerbils. The results
      in the gerbil differ considerably from age-dependent changes described for the
      rat IC, showing clear species-specific differences. 

PMID- 24879971
TI  - Oxidation scrutiny in persuaded aging and chronological aging at systemic redox
      homeostasis level.
AB  - BACKGROUND: The effect of the natural aging process on systemic redox homeostasis
      is previously documented. However, none of the studies specify the effect of
      experimental aging on systemic redox homeostasis. The purpose of this study is to
      clarify the ambiguity raised in preliminary reports as to mimetic aging
      dependency of the type and magnitude of oxidative damage on constituents of
      plasma. METHODS: In the current study, we investigated the interrelationship
      among various groups of the systemic oxidative damage markers such as protein
      oxidation products (protein carbonyl groups, protein hydroperoxides, advanced
      oxidation protein products, protein thiol groups), lipid peroxidation products
      (malondialdehyde, lipid hydroperoxides, conjugated dienes), glycoxidation adducts
      (advanced glycation end products), and antioxidant capacity (ferric
      reducing/antioxidant power, Cu,Zn-superoxide dismutase, total thiol, non-protein
      thiol). All these markers were measured in plasma of mimetically aged (MA) rats
      (5-month-old rats subjected to d-galactose-induced experimental aging), naturally
      aged (NA) rats (24-month-old), and their corresponding young controls (YC)
      (5months old). RESULTS AND CONCLUSIONS: Our current results show that systemic
      oxidation markers of the MA group share significant similarities in terms of
      impaired redox homeostasis with the NA rats and may be considered as a reliable
      experimental aging model for intravascular aging. Additional methodological
      studies including d-galactose dosage and application time are warranted to
      clarify the potential involvement of all these systemic redox variations as
      mechanistic factors in the development of mimetic aging related intravascular
      deterioration. Reversing or preventing systemic oxidative damage in experimental
      and natural aging should therefore be considered the primary target for the
      development of effective therapeutic strategies to prevent or treat age-related
      vascular disorders.

PMID- 24879974
TI  - Loop diuretic resistance in heart failure: resistance etiology-based strategies
      to restoring diuretic efficacy.
AB  - Loop diuretics are a cornerstone of symptom management for nearly all patients
      with heart failure. Diuretic resistance is a clinical problem with similar
      presentation despite diverse and multiple etiologies. Although the exact
      incidence is not known, diuretic resistance occurs frequently and can increase
      the length of hospitalization. Despite the prevalence of loop diuretic
      prescription in heart failure and frequency of diuretic resistance, current heart
      failure guidelines provide nonspecific guidance on strategies to restore diuretic
      efficacy. Providers are left with many questions regarding the optimum diuretic
      titration strategy in the setting of diuretic resistance. In light of these
      highly prevalent uncertainties, we present a case vignette-structured literature
      review of the mechanisms of diuretic resistance and recommend therapeutic
      strategies based on the resistance etiology to improve diuretic response in acute
      decompensated heart failure. 

PMID- 24879973
TI  - Expression of aquaporins in the lungs of mice with acute injury caused by LPS
      treatment.
AB  - The aim of the present study was to investigate the expression of aquaporin 1
      (AQP1) and AQP5 in the lungs of mice with acute injury induced by LPS treatment.
      In the study, the concentrations of cytokines were all significantly increased in
      the BALF of mice received LPS at 12h and 24h (P<0.001). The lung wet/dry weight
      ratios (W/D) and total protein content in BALF were also increased in the mice
      treated with LPS (P<0.001). Interestingly the expression of AQP1 and AQP5 was
      significantly decreased (P<0.05) compared with these in the control mice, while
      TUNEL positive cells were increased. However, the AQP5 expression was
      significantly higher at 24h that it at 12h in the control mice. Our results
      showed that decreased AQP expression was associated with the increased
      inflammatory factors, as well as apoptotic cells. The increased expression of
      AQP5 at 24h in control mice might be due to its regulation in transcellular water
      reabsorption. 

PMID- 24879976
TI  - Slow but steady progress in a field with many knowledge gaps.

PMID- 24879975
TI  - Inotrope use and outcomes among patients hospitalized for heart failure: impact
      of systolic blood pressure, cardiac index, and etiology.
AB  - BACKGROUND: Inotropes are widely used in hospitalized systolic heart failure (HF)
      patients, especially those with low systolic blood pressure (SBP) or cardiac
      index. In addition, inotropes are considered to be harmful in nonischemic HF.
      METHODS AND RESULTS: We examined the association of in-hospital inotrope use with
      (1) major events (death, ventricular assist device, or heart transplant) and (2)
      study days alive and out of hospital during the first 6 months in the Evaluation
      Study of Congestive Heart Failure and Pulmonary Artery Catheterization
      Effectiveness, which excluded patients with immediate need for inotropic therapy.
      Predefined subgroups of interest were baseline SBP <100 versus >= 100 mm Hg,
      cardiac index <1.8 vs >= 1.8 L min(-1) m(-2), and ischemic versus nonischemic HF
      etiology. Inotropes were frequently used in both the <100 mm Hg (88/165 [53.3%])
      and the >= 100 mm Hg (106/262 [40.5%]) SBP subgroups and were associated with
      higher risk for major events in both subgroups (adjusted hazard ratio [HR] 2.85,
      95% confidence interval [CI] 1.59-5.12 [P < .001]; and HR 1.86, 95% CI 1.02-3.37
      [P = .042]; respectively). Risk with inotropes was more pronounced among those
      with cardiac index >= 1.8 L min(-1) m(-2) (n = 114; HR 4.65, 95% CI 1.98-10.9; P
      < .001) vs <1.8 L min(-1) m(-2) (n = 82; HR 1.48, 95% CI 0.61-3.58; P = .39).
      Event rates were higher with inotropes in both ischemic (n = 215; HR 2.64, 95% CI
      1.49-4.68; P = .001) and nonischemic (n = 216; HR 2.19, 95% CI 1.18-4.07; P =
      .012) patients. Across all subgroups, patients who received inotropes spent fewer
      study days alive and out of hospital. CONCLUSIONS: In the absence of cardiogenic
      shock or end-organ hypoperfusion, inotrope use during hospitalization for HF was
      associated with unfavorable 6-month outcomes, regardless of admission SBP,
      cardiac index, or HF etiology.

PMID- 24879977
TI  - Epidemiology and risk factors for idiosyncratic drug-induced liver injury.
AB  - Idiosyncratic drug-induced liver injury (DILI) is, like other adverse effects of
      drugs, underreported and underestimated in most epidemiological studies based on
      registries of DILI cases and reporting systems (e.g., Medwatch). The same is
      probably true for prospective population-based studies, although they are much
      more likely to mirror the true incidence of DILI. Despite these challenges, the
      epidemiology of DILI remains of utmost importance and is gradually coming into
      better focus. A recent population based study found a crude incidence of ~19
      cases per 100,000 per year. Certain agents are particularly noteworthy for their
      DILI risk. Amoxicillin-clavulanate continues to be the most commonly implicated
      agent occurring in ~1 out of 2,300 users. Some others that standout with
      significantly higher risk include azathioprine and infliximab. Although statin
      induced hepatotoxicity has been well documented, the risk is probably quite low.
      Overall, the majority of DILI in children and adults is associated with either
      antibiotics or anticonvulsants. Drug-induced liver injury associated with
      intravenously given drugs does not show any major differences from DILI due to
      orally administered agents. Unfortunately, our understanding of pretherapy risk
      assessment remains rudimentary for the most part. 

PMID- 24879978
TI  - Genetic basis of drug-induced liver injury: present and future.
AB  - There is considerable evidence that susceptibility to idiosyncratic drug-induced
      liver injury (DILI) is genetically determined. Though genetic associations with
      DILI have been reported since the 1980s, the development of genome-wide
      association studies has enabled genetic risk factors for DILI, in common with
      other diseases, to be detected and confirmed more confidently. Human leukocyte
      antigen (HLA) genotype has been demonstrated to be a strong risk factor for
      development of DILI with a range of drugs and the underlying mechanism, probably
      involving presentation of a drug-peptide complex to T cells is increasingly well
      understood. However, specific HLA alleles are not associated with all forms of
      DILI and non-HLA genetic risk factors, especially those relating to drug
      disposition, also appear to contribute. For some drugs, there is evidence of a
      dual role for HLA and drug metabolism genes. Though the associations with non-HLA
      genes have been less well replicated than the HLA associations, there is
      increasing evidence that drug metabolism genes such as NAT2 and UGT2B7 contribute
      to some forms of DILI. Translating current genetic findings on DILI
      susceptibility to the clinic has been relatively slow, but some progress is now
      being made. In the future, DNA sequencing may lead to the identification of rare
      variants that contribute to DILI. Developments in the related area of epigenomics
      and in the development of improved models for DILI by use of genetically defined
      induced pluripotent stem cells should improve understanding of the biology of
      DILI and inform drug development. 

PMID- 24879979
TI  - Clinical features, diagnosis, and natural history of drug-induced liver injury.
AB  - Patients with idiosyncratic drug-induced liver injury (DILI) can pose substantial
      diagnostic, prognostic, and therapeutic challenges to the practicing
      gastroenterologist. The presentation of DILI may vary from asymptomatic liver
      enzyme elevation to acute liver failure. Although most DILI resolves following
      drug discontinuation, up to 20% of patients progress to chronic DILI further
      challenging the clinicians diagnostic and management skills. Also, some
      medications can lead to advanced fibrosis, encephalopathy, and portal
      hypertension without significant elevation in liver enzymes during exposure.
      Finally, there are no objective tests to definitively diagnose DILI. Although
      causality assessment instruments are available, none are widely accepted or used
      in clinical practice. Therefore, the diagnosis of DILI depends on thorough and
      accurate history taking, follow-up of the patient's clinical course and excluding
      more common causes of liver injury. In this review, we discuss the variable
      clinical presentations, course, and diagnostic methods used to establish a
      diagnosis and prognosis in DILI. 

PMID- 24879980
TI  - Drug-induced liver injury due to antimicrobials, central nervous system agents,
      and nonsteroidal anti-inflammatory drugs.
AB  - Antimicrobial agents including antituberculosis (anti-TB) agents are the most
      common cause of idiosyncratic drug-induced liver injury (DILI) and drug-induced
      liver failure across the world. Better molecular and genetic biomarkers are
      acutely needed to help identify those at risk of liver injury particularly for
      those needing antituberculosis therapy. Some antibiotics such as amoxicillin
      clavulanate and isoniazid consistently top the lists of agents in retrospective
      and prospective DILI databases. Central nervous system agents, particularly
      antiepileptics, account for the second most common class of agents implicated in
      DILI registries. Hepatotoxicity from older antiepileptics such as carbamazepine,
      phenytoin, and phenobarbital are often associated with hypersensitivity features,
      whereas newer antiepileptic drugs have a more favorable safety profile.
      Antidepressants and nonsteroidal anti-inflammatory drugs carry very low risk of
      significant liver injury, but their prolific use make them important causes of
      DILI. Early diagnosis and withdrawal of the offending agent remain the mainstays
      of minimizing hepatotoxicity. 

PMID- 24879981
TI  - Drug-induced liver injury due to cancer chemotherapeutic agents.
AB  - Drug-induced liver injury (DILI) due to chemotherapeutic drugs is a significant
      cause of morbidity and mortality. Most cases of chemotherapy-induced
      hepatotoxicity are idiosyncratic and do not have a unique clinical or
      histological signature that is distinct from other agents that cause DILI. The
      major mechanisms underlying chemotherapy-related hepatotoxicity are based on the
      production of reactive metabolites generated by phase I oxidation reactions,
      immunological injury, or alterations in mitochondrial function. Underlying liver
      disease and hepatic involvement by tumor are important modifiers of liver injury,
      and reversibility is not universal after drug cessation. Chemotherapy can also
      exacerbate underlying liver disease, particularly hepatitis B, leading to
      worsening hepatic function. Diagnosing DILI due to chemotherapeutic agents is
      particularly challenging because competing etiologies, such as hepatotoxicity
      from other medications, opportunistic infections, radiation therapy, and pre
      existing liver disease, are frequent. 

PMID- 24879982
TI  - Hepatotoxicity induced by herbal and dietary supplements.
AB  - Herbals and dietary supplements (HDS) can cause hepatotoxicity. Regulation of HDS
      varies across the globe. In the United States, it is defined by a law that is now
      two decades old. More recent regulatory approaches in Europe still do not require
      testing for premarket safety. The true incidence of hepatotoxicity from HDS is
      unknown. The presentation is most often with a hepatocellular enzyme pattern, and
      the outcomes can be severe, leading to transplantation in some circumstances. The
      diagnosis of hepatotoxicity due to HDS is made in the same way as for drugs.
      However, patients often must be coaxed into revealing a history of use. No
      causality assessment approach is perfectly suited for hepatotoxicity from HDS,
      but the Roussel Uclaf Causality Assessment Method is most used. Future endeavors
      must focus on defining epidemiology, establishing an accepted nomenclature, and
      identifying culprit ingredients, predisposing host factors, and useful biomarkers
      for injury. 

PMID- 24879983
TI  - Drug-induced liver injury with autoimmune features.
AB  - Drug-induced liver injury (DILI) with features of autoimmunity (AI) represents an
      important category of hepatotoxicity due to medication exposure. Drugs repeatedly
      associated with AI-DILI include diclofenac, alpha-methyl DOPA, hydralazine,
      nitrofurantoin, minocycline, and more recently statins and anti-TNF-alpha agents.
      Usually, symptoms of acute liver injury occur within a few months after
      initiation of a culprit medication, but a longer latency period is possible. Like
      idiopathic autoimmune hepatitis, circulating autoantibodies and a
      hypergammaglobulinemia are frequently present in sera from patients with AI-DILI.
      If performed, a liver biopsy should demonstrate interface hepatitis with a
      prominent plasma cell infiltrate. The severity of AI-DILI is variable, but a
      complete resolution after withdrawal of the offending medication is the
      expectation. A response to corticosteroid therapy supports the diagnosis, whereas
      a lack of recurrence of symptoms or signs following corticosteroid cessation
      distinguishes AI-DILI from idiopathic autoimmune hepatitis. 

PMID- 24879984
TI  - Drug-induced hepatic steatosis.
AB  - Several drugs have been associated with the potential for drug-induced hepatic
      steatosis (DIHS) and/or phospholipidosis (DIPL), a lysosomal storage disorder.
      Drug-induced hepatic steatosis is generally a chronic but reversible affliction
      and may involve drug accumulation in the liver. Fat accumulation may be either
      macrovesicular or microvesicular in nature. Commonly used medications associated
      with DIHS include amiodarone, valproate, tamoxifen, methotrexate, and some
      chemotherapeutic and antiretroviral agents. Two recently approved medications for
      the treatment of hereditary homozygous hypercholesterolemia have also been noted
      to cause hepatic steatosis. For some compounds such as methotrexate and
      tamoxifen, the underlying metabolic risk factors such as obesity and metabolic
      syndrome may exacerbate their potential to cause DIHS and its progression. In
      this article, the authors discuss the preclinical screening and mechanisms of
      DIHS and DIPL, and review specific examples of drugs commonly used in clinical
      practice that are known to cause DIHS. 

PMID- 24879985
TI  - DILI and drug development: a regulatory perspective.
AB  - The assessment of risk for serious, life-threatening drug-induced liver injury
      (DILI) associated with a suspect drug, biological agent, or herbal product
      depends on an iterative analysis of pre- and postmarket datastreams. Because
      serious cases of idiosyncratic DILI are typically rare, regulatory scientists
      seek strategies that accurately predict from clinical trial data which study
      drugs will be likely to cause these events in a large postmarket treatment
      population, e.g., through the identification of cases that are consistent with
      Hy's law. This objective is only achievable if rigorous standards in study
      subject monitoring, data collection and analysis of liver injury cases for
      causality are followed. In the future, the development of more effective
      predictive and analytic tools in preclinical and clinical testing will provide a
      framework to reliably identify new agents that have hepatotoxic profiles as well
      as those individuals who are susceptible to develop serious DILI. 

PMID- 24879986
TI  - Drug-induced liver injury and drug development: industry perspective.
AB  - Despite intensive ongoing research, drug-induced live injury (DILI) remains a
      serious issue for care providers and patients, and has been a major cause of drug
      withdrawal and non-approval by regulatory authorities in the past 50 years.
      Consequently, DILI remains a major concern for the pharmaceutical industry and a
      leading cause for attrition during drug development. In most instances, severe
      DILI is an uncommon idiosyncratic reaction, which typically does not present
      during preclinical phases or early clinical phases of drug development. In the
      majority of cases, drugs that caused severe DILI in humans have not shown clear
      and consistent hepatotoxic signals in preclinical assessment including animal
      studies, cell cultures, or other methods. Despite intensive efforts to develop
      better biomarkers that would help in predicting DILI risk in earlier phases of
      drug development, such biomarkers are currently not supported by sufficient
      evidence and are not yet available for routine use by drug makers. Due to the
      lack of effective and accurate methods for prediction of idiosyncratic DILI
      during preclinical phases of drug development, different drug makers have adopted
      different approaches, which are often not supported by strong systematic
      evidence. Based on growing experience, it is becoming increasingly evident that
      milder forms of liver injury occurring during clinical development, when assessed
      correctly, may significantly enhance our ability to predict the drug's potential
      to cause more severe liver injury postmarketing. Strategies based on this concept
      have been adopted by many drug makers, and are being increasingly implemented
      during drug development. Meticulous causality assessment of individual hepatic
      cases and adherence to strict hepatic discontinuation rules are critical
      components of this approach and have to rely on thorough clinical evaluation and
      occasionally on assessment by liver experts experienced with DILI and drug
      development. 

PMID- 24879987
TI  - Drug-induced nodular regenerative hyperplasia.
AB  - Drug-induced nodular regenerative hyperplasia is an uncommon injury with unique
      pathophysiology, clinical, and diagnostic considerations. This injury is
      characteristically asymptomatic in its early phases with only mild elevations in
      transaminases (< 3* upper limit of normal [ULN]). The latency period is typically
      more than 6 months. Once clinically apparent, it is marked by complications of
      portal hypertension, including hypersplenism, ascites, and variceal bleeding,
      with little or no hepatic dysfunction. Hence, it is an important cause of
      noncirrhotic portal hypertension. The most commonly associated drugs include
      thiopurines, chemotherapeutic agents, and antiretroviral agents. Diagnosis is
      aided by the recognition of noncirrhotic portal hypertension, a detailed history
      of prior drug exposure, and exclusion of the other causes of nodular regenerative
      hyperplasia. Clinical history, abdominal imaging, and hepatic hemodynamic studies
      provide important diagnostic clues, but histologic examination remains the
      diagnostic gold standard. Therapeutic intervention is aimed at earliest
      discontinuation of the offending agent and of portal hypertension complications.
      The natural history varies widely, and portal hypertension can progresses despite
      drug discontinuation. 

PMID- 24879988
TI  - Severe ductopenia and cholestasis from levofloxacin drug-induced liver injury: a
      case report and review.
AB  - A 67-year-old woman with hypertension, hypothyroidism, and glaucoma was referred
      for jaundice and elevated liver function tests. She was treated for streptococcal
      endophthalmitis with 2 weeks of intravenous (IV) levofloxacin followed by 2
      months of oral levofloxacin. The patient had no prior history of liver disease
      and denied alcohol intake. Her physical exam was remarkable for jaundice and
      scleral icterus without any stigmata of liver disease. Viral hepatitis serologies
      and antibodies, including myeloperoxidase, proteinase 3, and antinuclear,
      antimitochondrial, antiliver kidney microsome, antismooth muscle antibodies, were
      all within normal limits. The liver biopsy revealed severe cholestasis, extensive
      bile duct loss, and fibrosis. The patient had no known exposure to any other
      systemic medications or inciting factors other than levofloxacin. Although there
      are a few reported cases of drug-induced liver disease (DILI) related to
      levofloxacin, this case is believed to be the first reported case of ductopenia
      or vanishing bile duct syndrome (VBDS) associated with levofloxacin. Although
      fluoroquinolones, such as levofloxacin, are generally considered safe
      antibiotics, health practitioners must be aware of their association with DILI,
      as the diagnosis of DILI is one of exclusion and requires a high index of
      suspicion. 

PMID- 24879990
TI  - Roles of olfactory system dysfunction in depression.
AB  - The olfactory system is involved in sensory functions, emotional regulation and
      memory formation. Olfactory bulbectomy in rat has been employed as an animal
      model of depression for antidepressant discovery studies for many years.
      Olfaction is impaired in animals suffering from chronic stress, and patients with
      clinical depression were reported to have decreased olfactory function. It is
      believed that the neurobiological bases of depression might include dysfunction
      in the olfactory system. Further, brain stimulation, including nasal based drug
      delivery could provide novel therapies for management of depression. 

PMID- 24879991
TI  - PirB-Cry2Aa hybrid protein exhibits enhanced insecticidal activity against
      Spodoptera exigua larvae.
AB  - Previous study revealed that the N-terminal region of PirB toxin from
      Photorhabdus luminescens showed 20.5% identity and 41.5% similarity to the domain
      I of Cry2A toxin of Bacillus thuringiensis. The encoding sequence of the domain I
      of Cry2Aa protein was replaced by the encoding gene of corresponding domain of
      PirB protein. Expression of pirB-cry2Aa chimeric gene in B. thuringiensis
      acrystalliferous strain Cry(-)B leads to the formation of crystals with irregular
      shape. Bioassay showed that PirB-Cry2Aa hybrid protein displayed toxicity against
      Spodoptera exigua and Helicoverpa armigera larvae. Our data implied that PirB
      protein might possess pore-forming activity and PirB-Cry2Aa hybrid protein could
      be used as biological control agent. 

PMID- 24879992
TI  - The role of nicotinic receptors in shaping and functioning of the glutamatergic
      system: a window into cognitive pathology.
AB  - The involvement of the cholinergic system in learning, memory and attention has
      long been recognized, although its neurobiological mechanisms are not fully
      understood. Recent evidence identifies the endogenous cholinergic signaling via
      nicotinic acetylcholine receptors (nAChRs) as key players in determining the
      morphological and functional maturation of the glutamatergic system. Here, we
      review the available experimental and clinical evidence of nAChRs contribution to
      the establishment of the glutamatergic system, and therefore to cognitive
      function. We provide some clues of the putative underlying molecular mechanisms
      and discuss recent human studies that associate genetic variability of the genes
      encoding nAChR subunits with cognitive disorders. Finally, we discuss the new
      avenues to therapeutically targeting nAChRs in persons with cognitive dysfunction
      for which the alpha7-nAChR subunit is an important etiological mechanism. 

PMID- 24879993
TI  - Unusual ocular findings in identical twins.
AB  - We report an unusual case of dissimilar strabismus in monozygotic twins and
      describe the anatomical features which caused it.

PMID- 24879994
TI  - SNX-25a, a novel Hsp90 inhibitor, inhibited human cancer growth more potently
      than 17-AAG.
AB  - 17-Allylamino-17-demethoxygeldanamycin (17-AAG), a typical Hsp90 inhibitor
      derived from geldanamycin (GA), has entered Phase III clinical trials for cancer
      therapy. However, it has several significant limitations such as poor solubility,
      limited bioavailability and unacceptable hepatotoxicity. In this study, the
      anticancer activity and mechanism of SNX-25a, a novel Hsp90 inhibitor, was
      investigated comparing with that of 17-AAG. We showed that SNX-25a triggered
      growth inhibition more sensitively than 17-AAG against many human cancer cells,
      including K562, SW-620, A375, Hep-2, MCF-7, HepG2, HeLa, and A549 cell lines,
      especially at low concentrations (<1 MUM). It showed low cytotoxicity in L-02,
      HDF and MRC5 normal human cells. Compared with 17-AAG, SNX-25a was more potent in
      arresting the cell cycle at G2 phase, and displayed more potent effects on human
      cancer cell apoptosis and Hsp90 client proteins. It also exhibited a stronger
      binding affinity to Hsp90 than 17-AAG using molecular docking. Considering the
      superiority effects on Hsp90 affinity, cell growth, cell cycle, apoptosis, and
      Hsp90 client proteins, SNX-25a is supposed as a potential anticancer agent that
      needs to be explored in detail.

PMID- 24879996
TI  - Reflections on the Sidney ProjectTM: can we talk? Can we give voice to the taboo
      topics that are usually not embraced in residency medical education?

PMID- 24879995
TI  - Delirium diagnostic and classification challenges in palliative care:
      subsyndromal delirium, comorbid delirium-dementia, and psychomotor subtypes.
AB  - CONTEXT: Delirium often presents difficult diagnostic and classification
      challenges in palliative care settings. OBJECTIVES: To review three major areas
      that create diagnostic and classification challenges in relation to delirium in
      palliative care: subsyndromal delirium (SSD), delirium in the context of comorbid
      dementia, and classification of psychomotor subtypes, and to identify knowledge
      gaps and research priorities in relation to these three areas of focus. METHODS:
      We combined multidisciplinary input from delirium researchers and knowledge users
      at an international delirium study planning meeting and relevant PubMed
      literature searches as the knowledge synthesis strategy in this review. RESULTS:
      We identified six (SSD), 33 (dementia), and 44 (psychomotor subtypes) articles of
      relevance in relation to the focus of our review. Recent literature data
      highlight the frequency and impact of SSD, the relevance of comorbid dementia,
      and the propensity for a hypoactive presentation of delirium in the palliative
      population. The differential diagnoses to consider are wide and include pain,
      fatigue, mood disturbance, psychoactive medication effects, and other causes for
      altered consciousness. CONCLUSION: Challenges in the diagnosis and classification
      of delirium in people with advanced disease are compounded by the generalized
      disturbance of central nervous system function that occurs in the seriously ill,
      often with comorbid illness, including dementia. Further research is needed to
      delineate the pathophysiological and clinical associations of these presentations
      and thus inform therapeutic strategies. The expanding aged population and growing
      focus on dementia care in palliative care highlight the need to conduct this
      research.

PMID- 24879997
TI  - End-of-life delirium: issues regarding recognition, optimal management, and the
      role of sedation in the dying phase.
AB  - CONTEXT: In end-of-life care, delirium is often not recognized and poses unique
      management challenges, especially in the case of refractory delirium in the
      terminal phase. OBJECTIVES: To review delirium in the terminal phase context,
      specifically in relation to recognition issues; the decision-making processes and
      management strategies regarding its reversibility; the potential refractoriness
      of delirium to symptomatic treatment; and the role of sedation in refractory
      delirium. METHODS: We combined multidisciplinary input from delirium researchers
      and knowledge users at an international delirium study planning meeting and
      relevant electronic database literature searches (Ovid Medline, Embase, PsycINFO,
      and CINAHL) to inform this narrative review. RESULTS: The overall management
      strategy for delirium at the end of life is directed by the patient's prognosis
      in association with the patient's goals of care. As symptoms of delirium are
      often refractory in the terminal phase, especially in the case of agitated
      delirium, the judicious use of palliative sedation is frequently required.
      However, there remains a lack of high-level evidence for the management of
      delirium in the terminal phase, including the role of antipsychotics and optimal
      sedation strategies. For the family and health-care staff, clear communication,
      education, and emotional support are vital components to assist with decision
      making and direct the treatment care plan. CONCLUSION: Further research on the
      effectiveness of delirium management strategies in the terminal phase for
      patients and their families is required. Further validation of assessment tools
      for diagnostic screening and severity measurement is needed in this patient
      population.

PMID- 24879999
TI  - Subcutaneous use of baclofen.

PMID- 24879998
TI  - Ethical conduct of palliative care research: enhancing communication between
      investigators and institutional review boards.
AB  - Palliative care has faced moral and ethical challenges when conducting research
      involving human subjects. There are currently no resources to guide institutional
      review boards (IRBs) in applying standard ethical principles and terms-in a
      specific way-to palliative care research. Using as a case study a recently
      completed multisite palliative care clinical trial, this article provides
      guidance and recommendations for both IRBs and palliative care investigators to
      facilitate communication and attain the goal of conducting ethical palliative
      care research and protecting study participants while advancing the science.
      Beyond identifying current challenges faced by palliative care researchers and
      IRBs reviewing palliative care research, this article suggests steps that the
      palliative care research community can take to establish a scientifically sound,
      stable, productive, and well-functioning relationship between palliative care
      investigators and the ethical bodies that oversee their work. 

PMID- 24880000
TI  - EMPOWER: an intervention to address barriers to pain management in hospice.
AB  - CONTEXT: Concerns about pain medications are major barriers to pain management in
      hospice, but few studies have focused on systematic methods to address these
      concerns. OBJECTIVES: The objective of this study was to test the preliminary
      efficacy of the Effective Management of Pain: Overcoming Worries to Enable Relief
      (EMPOWER) intervention, which included hospice staff education, staff screening
      of barriers to pain management at admission, and discussion about
      misunderstandings regarding pain management with family caregivers and patients.
      METHODS: We conducted a pilot, cluster randomized, controlled trial with four
      hospices. One hundred twenty-six family caregivers (55 interventions and 71
      controls) were interviewed at two weeks after admission. If patients survived
      three months after admission, caregivers were reinterviewed. RESULTS: At two
      weeks, caregivers in the intervention group reported better knowledge about pain
      management (P = 0.001), fewer concerns about pain and pain medications (P =
      0.008), and lower patient pain over the past week (P = 0.014) and trended toward
      improvement in most other areas under study. Exploratory analyses suggest that
      EMPOWER had a greater effect for black subjects (vs. whites) on reducing concern
      about stigma. At three months, the intervention group trended better on most
      study outcomes. CONCLUSION: EMPOWER is a promising model to reduce barriers to
      pain management in hospice.

PMID- 24880001
TI  - Long-term psychosocial outcomes among bereaved siblings of children with cancer.
AB  - CONTEXT: The death of a child from cancer affects the entire family. Little is
      known about the long-term psychosocial outcomes of bereaved siblings. OBJECTIVES:
      To describe 1) the prevalence of risky health behaviors, psychological distress,
      and social support among bereaved siblings and 2) potentially modifiable factors
      associated with poor outcomes. METHODS: Bereaved siblings were eligible for this
      dual-center, cross-sectional, survey-based study if they were 16 years or older
      and their parents had enrolled in one of three prior studies about caring for
      children with cancer at the end of life. Linear regression models identified
      associations between personal perspectives before, during, and after the family's
      cancer experience and outcomes (health behaviors, psychological distress, and
      social support). RESULTS: Fifty-eight siblings completed surveys (62% response
      rate). They were approximately 12 years bereaved, with a mean age of 26 years at
      the time of the survey (SD 7.8). Anxiety, depression, and illicit substance use
      increased during the year after their brother/sister's death but then returned to
      baseline. Siblings who reported dissatisfaction with communication, poor
      preparation for death, missed opportunities to say goodbye, and/or a perceived
      negative impact of the cancer experience on relationships tended to have higher
      distress and lower social support scores (P < 0.001-0.031). Almost all siblings
      reported that their loss still affected them; half stated that the experience
      impacted current educational and career goals. CONCLUSION: How siblings
      experience the death of a child with cancer may impact their long-term
      psychosocial well-being. Sibling-directed communication and concurrent supportive
      care during the cancer experience and the year after the sibling death may
      mitigate poor long-term outcomes.

PMID- 24880002
TI  - Feasibility of using algorithm-based clinical decision support for symptom
      assessment and management in lung cancer.
AB  - CONTEXT: Distressing symptoms interfere with the quality of life in patients with
      lung cancer. Algorithm-based clinical decision support (CDS) to improve evidence
      based management of isolated symptoms seems promising, but no reports yet address
      multiple symptoms. OBJECTIVES: This study examined the feasibility of CDS for a
      Symptom Assessment and Management Intervention targeting common symptoms in
      patients with lung cancer (SAMI-L) in ambulatory oncology. The study objectives
      were to evaluate completion and delivery rates of the SAMI-L report and clinician
      adherence to the algorithm-based recommendations. METHODS: Patients completed a
      web-based symptom assessment and SAMI-L created tailored recommendations for
      symptom management. Completion of assessments and delivery of reports were
      recorded. Medical record review assessed clinician adherence to recommendations.
      Feasibility was defined as 75% or higher report completion and delivery rates and
      80% or higher clinician adherence to recommendations. Descriptive statistics and
      generalized estimating equations were used for data analyses. RESULTS: Symptom
      assessment completion was 84% (95% CI=81-87%). Delivery of completed reports was
      90% (95% CI=86-93%). Depression (36%), pain (30%), and fatigue (18%) occurred
      most frequently, followed by anxiety (11%) and dyspnea (6%). On average, overall
      recommendation adherence was 57% (95% CI=52-62%) and was not dependent on the
      number of recommendations (P=0.45). Adherence was higher for anxiety (66%; 95%
      CI=55-77%), depression (64%; 95% CI=56-71%), pain (62%; 95% CI=52-72%), and
      dyspnea (51%; 95% CI=38-64%) than for fatigue (38%; 95% CI=28-47%). CONCLUSION:
      The CDS systems, such as SAMI-L, have the potential to fill a gap in promoting
      evidence-based care.

PMID- 24880003
TI  - Bioactive glasses with improved processing. Part 1. Thermal properties, ion
      release and apatite formation.
AB  - Bioactive glasses, particularly Bioglass(r) 45S5, have been used to clinically
      regenerate human bone since the mid-1980s; however, they show a strong tendency
      to undergo crystallization upon heat treatment, which limits their range of
      applications. Attempts at improving their processing (by reducing their tendency
      to crystallize) have included increasing their silica content (and thus their
      network connectivity), incorporating intermediate oxides or reducing their
      phosphate content, all of which reduce glass bioactivity. Therefore, bioactive
      glasses known for their good processing (e.g. 13-93) are considerably less
      bioactive. Here, we investigated if the processing of 45S5 bioactive glass can be
      improved while maintaining its network connectivity and phosphate content. The
      results show that, by increasing the calcium:alkali cation ratio, partially
      substituting potassium for sodium (thereby making use of the mixed alkali effect)
      and adding small amounts of fluoride, bioactive glasses can be obtained which
      have a larger processing window (suggesting that they can be processed more
      easily, allowing for sintering of scaffolds or drawing into fibres) while
      degrading readily and forming apatite in aqueous solution within a few hours. 

PMID- 24880006
TI  - Flux analysis of the human proximal colon using anaerobic digestion model 1.
AB  - The colon can be regarded as an anaerobic digestive compartment within the gastro
      intestinal tract (GIT). An in silico model simulating the fluxes in the human
      proximal colon was developed on basis of the anaerobic digestion model 1 (ADM1),
      which is traditionally used to model waste conversion to biogas. Model
      calibration was conducted using data from in vitro fermentation of the proximal
      colon (TIM-2), and, amongst others, supplemented with the bio kinetics of
      prebiotic galactooligosaccharides (GOS) fermentation. The impact of water and
      solutes absorption by the host was also included. Hydrolysis constants of
      carbohydrates and proteins were estimated based on total short chain fatty acids
      (SCFA) and ammonia production in vitro. Model validation was established using an
      independent dataset of a different in vitro model: an in vitro three-stage
      continuous culture system. The in silico model was shown to provide quantitative
      insight in the microbial community structure in terms of functional groups, and
      the substrate and product fluxes between these groups as well as the host, as a
      function of the substrate composition, pH and the solids residence time (SRT).
      The model confirms the experimental observation that methanogens are washed out
      at low pH or low SRT-values. The in silico model is proposed as useful tool in
      the design of experimental setups for in vitro experiments by giving insight in
      fermentation processes in the proximal human colon. 

PMID- 24880005
TI  - Anti-influenza viral effects of honey in vitro: potent high activity of manuka
      honey.
AB  - BACKGROUND AND AIMS: Influenza viruses are a serious threat to human health and
      cause thousands of deaths annually. Thus, there is an urgent requirement for the
      development of novel anti-influenza virus drugs. Therefore, the aim of this study
      was to evaluate the anti-influenza viral activity of honey from various sources.
      METHODS: Antiviral activities of honey samples were evaluated using MDCK cells.
      To elucidate the possible mechanism of action of honey, plaque inhibition assays
      were used. Synergistic effects of honey with known anti-influenza virus drugs
      such as zanamivir or oseltamivir were tested. RESULTS: Manuka honey efficiently
      inhibited influenza virus replication (IC50 = 3.6 +/- 1.2 mg/mL; CC50 = 82.3 +/-
      2.2 mg/mL; selective index = 22.9), which is related to its virucidal effects. In
      the presence of 3.13 mg/mL manuka honey, the IC50 of zanamivir or oseltamivir was
      reduced to nearly 1/1000th of their single use. CONCLUSIONS: Our results showed
      that honey, in general, and particularly manuka honey, has potent inhibitory
      activity against the influenza virus, demonstrating a potential medicinal value.

PMID- 24880007
TI  - Antibody induction versus corticosteroid induction for liver transplant
      recipients.
AB  - BACKGROUND: Liver transplantation is an established treatment option for end
      stage liver failure. To date, no consensus has been reached on the use of
      immunosuppressive T-cell specific antibody induction compared with corticosteroid
      induction of immunosuppression after liver transplantation. OBJECTIVES: To assess
      the benefits and harms of T-cell specific antibody induction versus
      corticosteroid induction for prevention of acute rejection in liver transplant
      recipients. SEARCH METHODS: We searched The Cochrane Hepato-Biliary Group
      Controlled Trials Register, the Cochrane Central Register of Controlled Trials
      (CENTRAL), MEDLINE, EMBASE, Science Citation Index Expanded, and the World Health
      Organization (WHO) International Clinical Trials Registry Platform (ICTRP) on 30
      September 2013 together with reference checking, citation searching, contact with
      trial authors and pharmaceutical companies to identify additional trials.
      SELECTION CRITERIA: We included all randomised clinical trials assessing
      immunosuppression with T-cell specific antibody induction versus corticosteroid
      induction in liver transplant recipients. Our inclusion criteria stated that
      participants within each included trial should have received the same maintenance
      immunosuppressive therapy. DATA COLLECTION AND ANALYSIS: We used RevMan for
      statistical analysis of dichotomous data with risk ratio (RR) and of continuous
      data with mean difference (MD), both with 95% confidence intervals (CIs). We
      assessed risk of systematic errors (bias) using bias risk domains with
      definitions. We used trial sequential analysis to control for random errors (play
      of chance). MAIN RESULTS: We included 10 randomised trials with a total of 1589
      liver transplant recipients, which studied the use of T-cell specific antibody
      induction versus corticosteroid induction. All trials were with high risk of
      bias. We compared any kind of T-cell specific antibody induction versus
      corticosteroid induction in 10 trials with 1589 participants, including
      interleukin-2 receptor antagonist induction versus corticosteroid induction in
      nine trials with 1470 participants, and polyclonal T-cell specific antibody
      induction versus corticosteroid induction in one trial with 119 participants.Our
      analyses showed no significant differences regarding mortality (RR 1.01, 95% CI
      0.72 to 1.43), graft loss (RR 1.12, 95% CI 0.82 to 1.53) and acute rejection (RR
      0.84, 95% CI 0.70 to 1.00), infection (RR 0.96, 95% CI 0.85 to 1.09), hepatitis C
      virus recurrence (RR 0.89, 95% CI 0.79 to 1.00), malignancy (RR 0.59, 95% CI 0.13
      to 2.73), and post-transplantation lymphoproliferative disorder (RR 1.00, 95% CI
      0.07 to 15.38) when any kind of T-cell specific antibody induction was compared
      with corticosteroid induction (all low-quality evidence). Cytomegalovirus
      infection was less frequent in patients receiving any kind of T-cell specific
      antibody induction compared with corticosteroid induction (RR 0.50, 95% CI 0.33
      to 0.75; low-quality evidence). This was also observed when interleukin-2
      receptor antagonist induction was compared with corticosteroid induction (RR
      0.55, 95% CI 0.37 to 0.83; low-quality evidence), and when polyclonal T-cell
      specific antibody induction was compared with corticosteroid induction (RR 0.21,
      95% CI 0.06 to 0.70; low-quality evidence). However, when trial sequential
      analysis regarding cytomegalovirus infection was applied, the required
      information size was not reached. Furthermore, diabetes mellitus occurred less
      frequently when T-cell specific antibody induction was compared with
      corticosteroid induction (RR 0.45, 95% CI 0.34 to 0.60; low-quality evidence),
      when interleukin-2 receptor antagonist induction was compared with corticosteroid
      induction (RR 0.45, 95% CI 0.35 to 0.61; low-quality evidence), and when
      polyclonal T-cell specific antibody induction was compared with corticosteroid
      induction (RR 0.12, 95% CI 0.02 to 0.95; low-quality evidence). When trial
      sequential analysis was applied, the trial sequential monitoring boundary for
      benefit was crossed. We found no subgroup differences for type of interleukin-2
      receptor antagonist (basiliximab versus daclizumab). Four trials reported on
      adverse events. However, no differences between trial groups were noted. Limited
      data were available for meta-analysis on drug-specific adverse events such as
      haematological adverse events for antithymocyte globulin. No data were available
      on quality of life. AUTHORS' CONCLUSIONS: Because of the low quality of the
      evidence, the effects of T-cell antibody induction remain uncertain. T-cell
      specific antibody induction seems to reduce diabetes mellitus and may reduce
      cytomegalovirus infection when compared with corticosteroid induction. No other
      clear benefits or harms were associated with the use of T-cell specific antibody
      induction compared with corticosteroid induction. For some analyses, the number
      of trials investigating the use of T-cell specific antibody induction after liver
      transplantation is small, and the numbers of participants and outcomes in these
      randomised trials are limited. Furthermore, the included trials are heterogeneous
      in nature and have applied different types of T-cell specific antibody induction
      therapy. All trials were at high risk of bias. Hence, additional randomised
      clinical trials are needed to assess the benefits and harms of T-cell specific
      antibody induction compared with corticosteroid induction for liver transplant
      recipients. Such trials ought to be conducted with low risks of systematic error
      and of random error.

PMID- 24880009
TI  - Drug-induced liver injury: morbidity, mortality, and Hy's law.

PMID- 24880008
TI  - Unusual hepatic lesion in a patient with a lung tumor.

PMID- 24880012
TI  - Human exposure to trace metals and possible public health risks via consumption
      of mussels Mytilus galloprovincialis from the Adriatic coastal area.
AB  - Considering the growing concern due to different levels of anthropogenic
      loadings, the main purpose of this study was to identify the levels of trace
      metals (Fe, Mn, Cu, Zn, Co, Ni, Cd, Pb and Hg) in the mussels Mytilus
      galloprovincialis sampled along the marine coast of Boka Kotorska Bay,
      Montenegro. In comparison with the permissible limits set by the EU and the US
      FDA, all trace metal concentrations found in the mussels from the coastal area of
      Boka Kotorska Bay were lower than the prescribed limits. Generally, the trace
      metal concentrations found in Montenegrin mussels are within the range of trace
      metal concentrations determined in low to moderately polluted Adriatic areas.
      Based on these and other available literature data published by other authors for
      Adriatic region, the public health risks associated with the consumption of
      mussels in relation to reported trace metal concentrations were evaluated. In
      terms of the obtained trace metals concentrations in mussels and the provisional
      tolerable weekly intake prescribed by the JECFA and oral reference doses by the
      US EPA, the Pb and Cd concentrations and the Co and Cd concentrations were
      recognized as the limiting factor for the consumption of mussels from some
      Adriatic areas, respectively. 

PMID- 24880013
TI  - In vitro and in vivo safety evaluation of low molecular weight chitosans prepared
      by hydrolyzing crab shell chitosans with bamboo shoots chitosanase.
AB  - Our previous study demonstrated that the oral administration of low molecular
      weight chitosans (LMWC), prepared by hydrolyzing crab shell chitosans with bamboo
      shoots chitosanase in an appropriate dose, reduced aristolochic acid-induced
      renal lesions in mice. The objectives of this study were to evaluate the safety
      of LMWC using genetic and animal toxicity assays. Two assays for genotoxicity
      were performed: the chromosomal aberration of Chinese hamster ovary cells (CHO-K1
      cells) (in vitro) and micronucleus assays in mice (in vivo). Acute oral toxicity
      and 28-day repeated feeding toxicity tests were performed via the oral gavage
      method in Sprague-Dawley (SD) rats. LMWC did not induce an increase in
      micronucleus ratios in vivo, and the chromosome aberration assay indicated that
      the LMWC was safe in terms of clastogenicity in doses up to 5.0 mg/ml. No acute
      lethal effect at a maximum tested dose of 5.0 g LMWC/kg body weight (bw) was
      observed in rats. The results of the 28-day study revealed no adverse effects on
      the body weight, feed consumption, hematology, blood biochemical parameters,
      organ weights or pathology. The no observed adverse effect level (NOAEL) of LMWC
      in rats was 1.0 g/kg bw for the subacute toxicity study.

PMID- 24880014
TI  - An urgent need to reassess the safe levels of copper in the drinking water:
      lessons from studies on healthy animals harboring no genetic deficits.
AB  - Recent seminal studies have established neurodegeneration, cognitive waning
      and/or beta-amyloid deposition due to chronic copper intoxication via drinking
      water in healthy animals; henceforth, fuelling the debate all again over the safe
      levels of copper in the drinking water. This review encompasses the contemporary
      imperative animal studies in which the effect of chronic copper toxicity
      (especially via drinking water) was evaluated on the central nervous system and
      memory of uncompromised animals along with discussing the future perspectives. 

PMID- 24880016
TI  - Voltage-dependent anion channels (VDACs) promote mitophagy to protect neuron from
      death in an early brain injury following a subarachnoid hemorrhage in rats.
AB  - The term mitophagy is coined to describe the selective removal of mitochondria by
      autophagy but the process itself is still contentious, especially in the early
      period following subarachnoid hemorrhage (SAH). In the present study, we
      investigated the role of mitophagy following 48h after SAH injury in rats.
      Specifically evaluating whether mitophagy, through voltage dependant anion
      channels (VDACs) interacting with microtubule-associated protein 1 light chain 3,
      could orchestrate the induction of apoptotic and necrotic cell death in neurons,
      a VDAC1siRNA and an activitor Rapamycian (RAPA), were engaged. One hundred and
      twelve male Sprague-Dawley rats were randomly divided into 4 groups: Sham, SAH,
      SAH+VDAC1siRNA, and SAH+RAPA. Outcomes measured included mortality rate, brain
      edema, BBB disruption, and neurobehavioral testing. We also used western blotting
      techniques to analyze the expressions of key mitophagic/autophagic proteins and
      pro-apoptotic protein such as ROS, VDAC1, LC-3II and Caspase-3. Rapamycin
      treatment significantly improved the mortality rate, cerebral edema, and
      neurobehavioral deficits; apoptotic and necrotic cell death in neurons were
      reduced by Rapamycin following SAH injury. However, VDAC1siRNA worsened the brain
      injury following SAH. Immunohistochemical staining and western blot analysis
      demonstrated a decreased expression of VDAC1, LC3II, and an increase of ROS and
      Caspase-3 followed by VDAC1siRNA administration. In conclusion, mitophagy induced
      by VDAC1 following SAH injury may in fact play a significant role in
      neuroprotection, the mechanism which may be through the attenuation of the
      apoptosic and necrosic molecular pathways. This translates a preservation of
      functional integrity and an improvement in mortality. 

PMID- 24880017
TI  - Effects of clofibric acid alone and in combination with 17beta-estradiol on mRNA
      abundance in primary hepatocytes isolated from rainbow trout.
AB  - Clofibric acid (CA) is the active substance of lipid lowering drugs. It is
      resistant to degradation, polar in nature, and has been found ubiquitously in the
      aquatic environment. Though CA is classified as a peroxisomal proliferator in
      rodents and is considered as a potential endocrine disruptor, little information
      exists on the effects of CA in aquatic organisms, such as fish. In the present
      study, we examined the mRNA levels of peroxisome proliferator- and estrogen
      sensitive genes on the exposure of primary rainbow trout (Oncorhynchus mykiss)
      hepatocytes to CA alone and in combination with the natural female sex hormone,
      17beta-estradiol (E2). Our results demonstrate that rainbow trout hepatocytes are
      relatively refractory to the effects of CA on the PPAR signaling pathway and
      lipid metabolism. Moreover, CA did not show recognizable estrogenic activity, but
      after the induction of vitellogenesis by E2, CA significantly reduced
      vitellogenin (VTG) mRNA abundance. Apparently, the indirect repression of VTG
      transcription, independent of estrogen receptors, occurred. The mechanism is not
      yet clearly understood but may involve disruption of the stabilization of VTG
      mRNA known to be induced by E2. 

PMID- 24880018
TI  - Patency of skeletonized versus pedicled internal thoracic artery in coronary
      bypass graft surgery: a systematic review, meta-analysis and meta-regression.
AB  - BACKGROUND: It is suggested that the skeletonization harvesting technique
      influences the patency rates of internal thoracic artery (ITA) after coronary
      artery bypass graft (CABG) surgery in comparison to conventional (pedicled)
      harvesting. We conducted a meta-analysis to determine whether there is any
      difference between skeletonized versus pedicled ITA in terms of patency after
      CABG. METHODS: We performed a systematic-review using MEDLINE, EMBASE,
      CENTRAL/CCTR, SciELO, LILACS, Google Scholar and reference lists of relevant
      articles to search for studies that performed angiographic evaluation within the
      first two years after CABG between these two groups until December 2013. The
      principal summary measures were odds ratio (OR) with 95% Confidence Interval (CI)
      and P values (statistically significant when <0.05). The OR's were combined
      across studies using weighted DerSimonian-Laird random effects model and weighted
      Mantel-Haenszel fixed effects. Meta-analysis, sensitivity analysis and meta
      regression were completed using the software Comprehensive Meta-Analysis version
      2 (Biostat Inc., Englewood, New Jersey). RESULTS: Five studies involving 1764
      evaluated conduits (1145 skeletonized; 619 pedicled) met the eligibility
      criteria. There was no evidence for important heterogeneity of effects among the
      studies. The overall OR (95% CI) for graft occlusion showed no statistical
      significant difference between groups (fixed effect model: OR 1.351, 95% CI 0.408
      to 4.471, P = 0.801; random effect model: OR 1.351, 95% CI 0.408 to 4.471, P =
      0.801). In sensitivity analysis, no difference regarding to left or right ITA was
      also observed. In meta-regression, we observed no statistically significant
      coefficients for graft occlusion and proportion of female, diabetics, renal
      failure, age, off-pump surgery or urgency, which means that the effect is not
      modulated by these factors. CONCLUSION: In terms of patency, skeletonized ITA
      appears to be non-inferior in comparison to pedicled ITA after CABG.

PMID- 24880019
TI  - Ursolic acid ameliorates carbon tetrachloride-induced oxidative DNA damage and
      inflammation in mouse kidney by inhibiting the STAT3 and NF-kappaB activities.
AB  - Ursolic acid (UA), a common pentacyclic triterpenoid compound, has been reported
      to have many benefits and medicinal properties. However, its protective effects
      against carbon tetrachloride (CCl4) induced injury in kidneys are not yet clear.
      In the current report, we investigated whether UA inhibited the oxidative stress
      and inflammation in the kidneys of CCl4 treated mice. Male ICR mice were injected
      with CCl4 with or without UA co-administration (25 and 50mg/kg intragastrically
      once daily) for six weeks. Our data showed that UA significantly prevented CCl4
      induced nephrotoxicity in a dose-dependent manner, indicated by both diagnostic
      indicators of kidney damage and histopathological analysis. Moreover, CCl4
      induced profound elevation of ROS and oxidative stress, as evidenced by the
      increase of lipid peroxidation level and the depletion of the total antioxidant
      capacity (TAC) level in the kidney, was suppressed by treatment with UA. UA also
      decreased 8-hydroxy-2-deoxyguanosine (one product of oxidative DNA damage)
      levels. Furthermore, protein expression by Western blot analysis showed that UA
      significantly decreased production of pro-inflammatory markers including tumor
      necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), interleukin-17 (IL-17)
      and cyclooxygenase-2 (COX-2) in CCl4-treated mouse kidney. In exploring the
      underlying mechanisms of UA action, we found that UA increased the
      phosphorylation of transcription 3 (STAT3), which in turn activated the nuclear
      factor kappa B (NF-kappaB) and the inflammatory cytokines in the kidneys. In
      conclusion, these results suggested that the inhibition of CCl4-induced
      inflammation by UA is due at least in part to its anti-oxidant activity and its
      ability to modulate the STAT3 and NF-kappaB signaling pathways.

PMID- 24880020
TI  - Mobilization-driven postconsolidation therapy in elderly patients with acute
      myeloid leukemia: feasibility and efficacy of autologous stem cell
      transplantation versus low-dose gemtuzumab ozogamicin.
AB  - We prospectively evaluated 2 postconsolidation strategies, administered according
      to the mobilization outcome, in 72 acute myeloid leukemia (AML) fit elderly
      patients, achieving complete remission after the first high-dose cytarabine-based
      induction. Autologous stem cell transplantation (ASCT) was performed in patients
      collecting >=3 * 10(6) CD34(+)/kg and low-dose gemtuzumab ozogamicin (GO) was
      performed in poor mobilizers (collecting <3 * 10(6) CD34(+)/kg). Fifty-five
      patients (76.3%) underwent peripheral blood stem cell (PBSC) mobilization, after
      first consolidation, and 24 of 55 (44%) collected >3 * 10(6) CD34(+) cells/kg.
      Among the 55 patients eligible for PBSC mobilization, 7 did not receive the
      planned treatment, 23 were allocated for ASCT, and 25 were allocated for GO on an
      intention-to-treat basis. With a median follow-up of 70 months (range, 24 to
      124), 20 of 55 patients are alive, 18 of them in continuous complete remission.
      The 8-year overall survival (OS) and disease-free survival (DFS) are,
      respectively, 35.9% (95% confidence interval [CI] 24% to 49.8%) and 31.2% (95%
      CI, 21% to 43.8%), median OS and DFS were 22 and 16 months, respectively. In
      multivariate analysis, postconsolidation treatment and hyperleukocytosis (WBC >
      50,000/MUL) significantly predicted OS and DFS, whereas secondary AML was
      significantly associated with a higher relapse rate (83.4% versus 54% of de novo
      AML). Patients with hyperleukocytosis had 0% 3-year OS versus the 46% (at 8
      years) in patients without hyperleukocytosis (P = .01); 57% of patients in the GO
      arm are alive at 8 years, compared with 25.4% of patients in the ASCT arm, who
      had an overall relative risk (RR) of death of 2.6 (95% CI, 1.2 to 5.8; P = .02).
      DFS at 8 years was 45.3% in patients receiving GO, compared with 26% in ASCT arm
      (RR, 2.1; 95% CI, 1 to 4.3; P = .05). Our study outlines low feasibility and
      efficacy of ASCT in elderly AML patients, whereas postconsolidation with GO
      appears safe and effective in this unfavorable setting. The study was registered
      at Umin Clinical Trial Registry (www.umin.ac.jp/ctr), number R000014052. 

PMID- 24880022
TI  - Influence of autapse on mode-locking structure of a Hodgkin-Huxley neuron under
      sinusoidal stimulus.
AB  - We investigated the mode-locking behaviors of a Hodgkin-Huxley neuron with an
      autapse under sinusoidal stimulus. A neuron without an autapse can exhibit rich
      p:q mode-locking (i.e. p output action potentials generated by q cycles
      stimulations) behaviors with periodic stimuli. In the presence of the autaptic
      connection, the p:q mode-locking behaviors are completely reset. The autapse
      extends the scope of mode-locking. The autapse can enhance or suppress the status
      of mode-locking. Even for some specified autaptic parameters, the neuron could be
      driven into the sub-threshold oscillation. Our results suggested that the autapse
      can serve as a potential control option for adjusting the mode-locking firing
      behaviors. We also found that changing the delay time is much more effectively
      operable to regulate the response behavior than the autaptic intensity. 

PMID- 24880023
TI  - Reconceiving autoimmunity: An overview.
AB  - Three interconnected positions are advocated: (1) although serving as a useful
      model, the immune self does not exist as such; (2) instead of a self/nonself
      demarcation, the immune system 'sees' itself, i.e., it does not ignore the 'self'
      or attack the 'other;' but exhibits a spectrum of responses, which when viewed
      from outside the system appear as discrimination of 'self' and 'nonself' based on
      certain criteria of reactivity. When immune reactions are conceived in terms of
      normal physiology and open exchange with the environment, where borders dividing
      host and foreign are elusive and changing, host defense is only part of the
      immune system's functions, which actually comprise two basic tasks: protection,
      i.e., to preserve host integrity, and maintenance of organismic identity. And
      thus (3) if the spectrum of immunity is enlarged, differentiating low reactive
      'autoimmune' reactions from activated immune responses against the 'other' is
      only a matter of degree. Simply, all immunity is 'autoimmunity,' and the
      pathologic state of immunity directed at normal constituents of the organism is a
      particular case of dis-regulation, which appropriately is designated, autoimmune.
      Other uses of 'autoimmunity' and its congeners function as the semantic remnants
      of Burnet's original self/nonself theory and should be replaced. A new
      nomenclature is proposed, concinnity, which more accurately designates the
      physiology of the animal's ordinary housekeeping economy mediated by the immune
      system than 'autoimmunity' when used to describe such normal functions. 

PMID- 24880021
TI  - Outcomes of human leukocyte antigen-matched sibling donor hematopoietic cell
      transplantation in chronic lymphocytic leukemia: myeloablative versus reduced
      intensity conditioning regimens.
AB  - Allogeneic hematopoietic cell transplantation (HCT) can cure some chronic
      lymphocytic leukemia (CLL) subjects. This study compared outcomes of
      myeloablative (MA) and reduced-intensity conditioning (RIC) transplants from HLA
      matched sibling donors (MSD) for CLL. From 1995 to 2007, information regarding
      297 CLL subjects was reported to the Center of International Blood and Marrow
      Transplant Research; of these, 163 underwent MA and 134 underwent RIC MSD HCT.
      The MA subjects underwent transplantation less often after 2000 and less commonly
      received antithymocyte globulin (4% versus 13%, P = .004) or prior antibody
      therapy (14% versus 53%; P < .001). RIC was associated with a greater likelihood
      of platelet recovery and less grade 2 to 4 acute graft-versus-host disease
      compared with MA conditioning. One- and 5-year treatment-related mortality (TRM)
      were 24% (95% confidence intervals [CI], 16% to 33%) versus 37% (95% CI, 30% to
      45%; P = .023), and 40% (95% CI, 29% to 51%) versus 54% (95% CI, 46% to 62%; P =
      .036), respectively, and the relapse/progression rates at 1 and 5 years were 21%
      (95% CI, 14% to 29%) versus 10% (95% CI, 6% to 15%; P = .020), and 35% (95% CI,
      26% to 46%) versus 17% (95% CI, 12% to 24%; P = .003), respectively. MA
      conditioning was associated with better progression-free (PFS) (relative risk,
      .60; 95% CI, .37 to .97; P = .038) and 3-year survival in transplantations before
      2001, but for subsequent years, RIC was associated with better PFS and survival
      (relative risk, 1.49 [95% CI, .92 to 2.42]; P = .10; and relative risk, 1.86 [95%
      CI, 1.11 to 3.13]; P = .019). Pretransplantation disease status was the most
      important predictor of relapse (P = .003) and PFS (P = .0007) for both forms of
      transplantation conditioning. MA and RIC MSD transplantations are effective for
      CLL. Future strategies to decrease TRM and reduce relapses are warranted. 

PMID- 24880024
TI  - Can antibodies against flies alter malaria transmission in birds by changing
      vector behavior?
AB  - Transmission of insect-borne diseases is shaped by the interactions among
      parasites, vectors, and hosts. Any factor that alters movement of infected
      vectors from infected to uninfeced hosts will in turn alter pathogen spread. In
      this paper, we study one such pathogen-vector-host system, avian malaria in
      pigeons transmitted by fly ectoparasites, where both two-way and three-way
      interactions play a key role in shaping disease spread. Bird immune defenses
      against flies can decrease malaria prevalence by reducing fly residence time on
      infected birds or increase disease prevalence by enhancing fly movement and thus
      infection transmission. We develop a mathematical model that illustrates how
      these changes in vector behavior influence pathogen transmission and show that
      malaria prevalence is maximized at an intermediate level of defense avoidance by
      the flies. Understanding how host immune defenses indirectly alter disease
      transmission by influencing vector behavior has implications for reducing the
      transmission of human malaria and other vectored pathogens. 

PMID- 24880025
TI  - Urinary microRNA profiling for identification of biomarkers after cisplatin
      induced kidney injury.
AB  - Extracellular microRNAs (miRNAs) have emerged as novel biomarkers (BMs) for
      various pathological states. To evaluate whether urinary miRNAs could serve as
      biomarkers for drug-induced kidney injury, we performed a nephrotoxicity study in
      rats with cisplatin (Cp), which is known to induce renal proximal tubular lesions
      in several species. Male Wistar rats were treated with a single dose of Cp (0, 1
      and 3mg/kg) and urine was collected on days 3, 5, 8, 15 and 26 for measurement of
      several biomarkers and for RNA isolation. MiRNA profiling experiments with urine
      samples derived from the 3mg/kg Cp dosed animals, identified 136 miRNAs
      significantly increased in urine 3 and 5 days after Cp administration. 18 miRNAs
      with distinct time-dependent profiles were further analyzed using specific miRNA
      assays and absolute quantification. We observed >20-fold changes for 11 of these
      18 miRNAs measured in profiling experiments, and confirmed their direction of
      change and time course profile by absolute quantification. Furthermore we found
      mechanistic links between several miRNAs and simultaneously measured mRNAs in the
      kidney after Cp administration. These were associated with pathways suggested to
      be involved in Cp-induced nephrotoxicity including a DNA damage response,
      apoptosis, and cell cycle regulation. Overall our results indicate that miRNAs
      measured in urine may serve as BMs for nephrotoxicity in rats. 

PMID- 24880026
TI  - Naringin, a flavanone glycoside, promotes angiogenesis and inhibits endothelial
      apoptosis through modulation of inflammatory and growth factor expression in
      diabetic foot ulcer in rats.
AB  - Chronic, unhealed diabetic foot ulcer (DFU) is one of the most severe
      complications of diabetes mellitus (DM). Naringin, a flavanone glycoside
      antioxidant, was reported to have antidiabetic and anti-apoptotic properties. In
      the present study DM was induced experimentally by streptozotocin (STZ, 55 mg/kg,
      i.p.). In surgically introduced wounds on the dorsal surface of the hind paw of
      rats, the healing potential of naringin was investigated. Rats were treated with
      naringin (20, 40 and 80 mg/kg, p.o.), insulin (10 IU/kg, s.c.) and
      tetrachlorodecaoxide (TCDO) (1 drop, twice a day, topically) for 16 days. The
      wound area was measured every second day, and on day 17 various biochemical
      parameters were determined in serum, wound tissue, and histopathological
      examination of the wound was performed. Naringin (40 and 80 mg/kg) significantly
      (P<0.05) improved wound area, serum glucose level, glycated Hb and serum insulin.
      Naringin treatment at 40 and 80 mg/kg resulted in significant (P<0.05) up
      regulation of mRNA expression of growth factor (IFG-1, TGF-beta and VEGF-c), Ang
      1 and collagen-1 whereas mRNA expression of inflammatory mediators (TNF-alpha, IL
      1beta and IL-6) was down-regulated. Furthermore, naringin significantly (P<0.05)
      attenuated STZ-induced apoptosis and stimulated angiogenesis in the wound tissue.
      Further results suggest that angiogenesis was improved via naringin-mediated
      inhibition of hyperglycemia, oxidative stress, down-regulation of inflammatory
      mediator expression and up-regulation of growth factor expression, leading to
      improved wound healing of DFU.

PMID- 24880028
TI  - Flaviviruses are neurotropic, but how do they invade the CNS?
AB  - Flaviruses (FV) are RNA viruses carried by mosquitoes. Neurological signs
      including acute encephalitis, meningitis and acute flaccid paralysis develop in a
      small percentage of infected individuals; long term sequlae are, Parkinsonism,
      dystonias and cognitive changes. FV neuroinfection is neurotropic involving
      subcortical nuclei (substantia nigra and thalamus) anterior horn neurons and
      neocortex. Glycosylation of the FV E envelope protein is one determinant of
      neuroinvasion, increasing both axonal and trans-epithelial transportation.
      Neutralizing antibodies against the E and NS proteins prevents FV uptake into
      several cell types, including axons. CD8+ T cells are vital for clearance of WNF
      infected cells from the CNS, whereas TLR-3 and TLR-7 mediated anti-virus response
      through increased serum inflammatory cytokines to disrupt the BBB providing
      infected leucocytes and free virus access to the CNS (so called Trojan horse)
      Cellular virus attachment factors, promoting FV cell entry are widely distributed
      and include DC-SIGN (that detects complex carbohydrate molecules); Glycosamino
      glycans (GAG), Heparan sulphate(HSPG) Semaphorin 7A, Low Density Lipid receptors
      (LDLR); these are not FV specific virus entry receptors. The FV also crosses
      epithelial and endothelial barriers by disrupting Tight Junction complexes to
      increase BBB permeability. This review describes the multiple pathways
      responsible for the neuroinvasive properties of the Flaviviruses. 

PMID- 24880027
TI  - The genetics of auricular development and malformation: new findings in model
      systems driving future directions for microtia research.
AB  - Microtia is a term used to describe a wide array of phenotypic presentations of
      the outer ear. Although the majority of the cases are isolated in nature, much of
      our understanding of the causes of microtia has been driven by the identification
      of genes underlying syndromic forms where the anomaly co-presents with various
      other craniofacial and extra-craniofacial structural defects. In this review we
      discuss recent findings in mice deficient in Hoxa2, a key regulator of branchial
      arch patterning, which has necessitated a revision to the canonical model of
      pinna morphogenesis. The revised model will likely impact current classification
      schemes for microtia and, as we argue in this review, the interpretation of the
      developmental basis for various auricular malformations. In addition, we
      highlight recent studies in other mammalian species that are providing the first
      clues as to possible causes of at least some isolated anomalies and thus should
      now accelerate the search for the more elusive genetic contributions to the many
      isolated and non-syndromic cases of microtia. These findings, together with the
      application of new genome-level sequencing technologies and more thorough
      quantitative assessment of available mutant mouse resources, promise an exciting
      future for genetic studies in microtia. 

PMID- 24880029
TI  - Impact of microbial ecology on accuracy of surveillance cultures to predict
      multidrug resistant microorganisms causing ventilator-associated pneumonia.
AB  - OBJECTIVES: The objective of this study was to assess surveillance cultures (SC)
      prediction accuracy in two periods and settings of the same Department with a
      different microbiological epidemiology (high and low prevalence of multi-drug
      resistant microorganisms (MDRM)). METHODS: Prospective and observational study.
      SC were obtained twice a week in consecutive mechanically ventilated patients.
      Patients fulfilling VAP criteria were analyzed. RESULTS: 440 patients were
      followed up, 71 patients had VAP (50 in period I and 21 in period II). MDRM
      causing VAP were more prevalent in the first period (48% vs. 19%; p = 0.033). The
      rate of empirical appropriate treatment in period I was lower than in period II
      (52% vs.76%; p = 0.031). SC prediction accuracy was similar in the two periods
      (80% vs. 81%; p = 0.744). However, if antibiotic treatment had been guided by SC,
      the percentage of appropriate treatment would have increased by 28% in the first
      period but only by 5% in the second; p = 0.024. CONCLUSIONS: SC were able to
      predict VAP etiology in 80% of cases regardless the prevalence of MDRM. However,
      the potential benefit of SC in terms of appropriate empirical treatment could be
      only observed when MDRM were prevalent.

PMID- 24880030
TI  - Reply to Krause et al.

PMID- 24880031
TI  - HMG CoA reductase inhibitors (statins) for people with chronic kidney disease not
      requiring dialysis.
AB  - BACKGROUND: Cardiovascular disease (CVD) is the most frequent cause of death in
      people with early stages of chronic kidney disease (CKD), for whom the absolute
      risk of cardiovascular events is similar to people who have existing coronary
      artery disease. This is an update of a review published in 2009, and includes
      evidence from 27 new studies (25,068 participants) in addition to the 26 studies
      (20,324 participants) assessed previously; and excludes three previously included
      studies (107 participants). This updated review includes 50 studies (45,285
      participants); of these 38 (37,274 participants) were meta-analysed. OBJECTIVES:
      To evaluate the benefits (such as reductions in all-cause and cardiovascular
      mortality, major cardiovascular events, MI and stroke; and slow progression of
      CKD to end-stage kidney disease (ESKD)) and harms (muscle and liver dysfunction,
      withdrawal, and cancer) of statins compared with placebo, no treatment, standard
      care or another statin in adults with CKD who were not on dialysis. SEARCH
      METHODS: We searched the Cochrane Renal Group's Specialised Register to 5 June
      2012 through contact with the Trials' Search Co-ordinator using search terms
      relevant to this review. SELECTION CRITERIA: Randomised controlled trials (RCTs)
      and quasi-RCTs that compared the effects of statins with placebo, no treatment,
      standard care, or other statins, on mortality, cardiovascular events, kidney
      function, toxicity, and lipid levels in adults with CKD not on dialysis were the
      focus of our literature searches. DATA COLLECTION AND ANALYSIS: Two or more
      authors independently extracted data and assessed study risk of bias. Treatment
      effects were expressed as mean difference (MD) for continuous outcomes (lipids,
      creatinine clearance and proteinuria) and risk ratio (RR) for dichotomous
      outcomes (major cardiovascular events, all-cause mortality, cardiovascular
      mortality, fatal or non-fatal myocardial infarction (MI), fatal or non-fatal
      stroke, ESKD, elevated liver enzymes, rhabdomyolysis, cancer and withdrawal
      rates) with 95% confidence intervals (CI). MAIN RESULTS: We included 50 studies
      (45,285 participants): 47 studies (39,820 participants) compared statins with
      placebo or no treatment and three studies (5547 participants) compared two
      different statin regimens in adults with CKD who were not yet on dialysis. We
      were able to meta-analyse 38 studies (37,274 participants).The risk of bias in
      the included studies was high. Seven studies comparing statins with placebo or no
      treatment had lower risk of bias overall; and were conducted according to
      published protocols, outcomes were adjudicated by a committee, specified outcomes
      were reported, and analyses were conducted using intention-to-treat methods. In
      placebo or no treatment controlled studies, adverse events were reported in 32
      studies (68%) and systematically evaluated in 16 studies (34%).Compared with
      placebo, statin therapy consistently prevented major cardiovascular events (13
      studies, 36,033 participants; RR 0.72, 95% CI 0.66 to 0.79), all-cause mortality
      (10 studies, 28,276 participants; RR 0.79, 95% CI 0.69 to 0.91), cardiovascular
      death (7 studies, 19,059 participants; RR 0.77, 95% CI 0.69 to 0.87) and MI (8
      studies, 9018 participants; RR 0.55, 95% CI 0.42 to 0.72). Statins had uncertain
      effects on stroke (5 studies, 8658 participants; RR 0.62, 95% CI 0.35 to
      1.12).Potential harms from statin therapy were limited by lack of systematic
      reporting and were uncertain in analyses that had few events: elevated creatine
      kinase (7 studies, 4514 participants; RR 0.84, 95% CI 0.20 to 3.48), liver
      function abnormalities (7 studies, RR 0.76, 95% CI 0.39 to 1.50), withdrawal due
      to adverse events (13 studies, 4219 participants; RR 1.16, 95% CI 0.84 to 1.60),
      and cancer (2 studies, 5581 participants; RR 1.03, 95% CI 0.82 to 130).Statins
      had uncertain effects on progression of CKD. Data for relative effects of
      intensive cholesterol lowering in people with early stages of kidney disease were
      sparse. Statins clearly reduced risks of death, major cardiovascular events, and
      MI in people with CKD who did not have CVD at baseline (primary prevention).
      AUTHORS' CONCLUSIONS: Statins consistently lower death and major cardiovascular
      events by 20% in people with CKD not requiring dialysis. Statin-related effects
      on stroke and kidney function were found to be uncertain and adverse effects of
      treatment are incompletely understood. Statins have an important role in primary
      prevention of cardiovascular events and mortality in people who have CKD.

PMID- 24880035
TI  - Sequence diversity and gene expression analyses of expansin-related proteins in
      the white-rot basidiomycete, Phanerochaete carnosa.
AB  - Expansin and expansin-related proteins loosen plant cell wall architectures and
      are widely distributed in several types of organisms, including plants, fungi and
      bacteria. Here we describe sequence diversity and unique gene expression profiles
      of multiple expansin-related proteins identified in the basidiomycete,
      Phanerochaete carnosa. The protein sequences were homologous to loosenin, an
      expansin-related protein reported in the basidiomycete, Bjerkandera adusta. We
      identified homologous sequences of each of those P. carnosa proteins in many
      basidiomycete species. Twelve P. carnosa loosenin-like proteins (LOOLs) were
      classified into two subgroups according to sequence homology. Conservation of
      polysaccharide-binding amino acid residues was stricter in subgroup A. Subgroup A
      sequences included a conserved 8-9 amino acid insertion in a polysaccharide
      binding groove whereas subgroup B contained a 12-18 amino acid insertion next to
      the binding groove. The P. carnosa genome also encodes the expansin-related
      protein, DREX1, which adopts a loosenin-like structure but has lower sequence
      homology to other LOOLs. The gene expression analysis of those proteins showed
      distinct patterns that were not significantly related to subgroupings. The
      variation in the protein sequences and gene expression patterns, and wide
      distribution among the basidiomycota, suggest that the diverse cell wall
      loosening proteins contribute to effective plant cell wall association and
      utilization by basidiomycetes. 

PMID- 24880036
TI  - Tissue engineering in dentistry.
AB  - OBJECTIVES: of this review is to inform practitioners with the most updated
      information on tissue engineering and its potential applications in dentistry.
      DATA: The authors used "PUBMED" to find relevant literature written in English
      and published from the beginning of tissue engineering until today. A combination
      of keywords was used as the search terms e.g., "tissue engineering",
      "approaches", "strategies" "dentistry", "dental stem cells", "dentino-pulp
      complex", "guided tissue regeneration", "whole tooth", "TMJ", "condyle",
      "salivary glands", and "oral mucosa". SOURCES: Abstracts and full text articles
      were used to identify causes of craniofacial tissue loss, different approaches
      for craniofacial reconstructions, how the tissue engineering emerges, different
      strategies of tissue engineering, biomaterials employed for this purpose, the
      major attempts to engineer different dental structures, finally challenges and
      future of tissue engineering in dentistry. STUDY SELECTION: Only those articles
      that dealt with the tissue engineering in dentistry were selected. CONCLUSIONS:
      There have been a recent surge in guided tissue engineering methods to manage
      periodontal diseases beyond the traditional approaches. However, the predictable
      reconstruction of the innate organisation and function of whole teeth as well as
      their periodontal structures remains challenging. Despite some limited progress
      and minor successes, there remain distinct and important challenges in the
      development of reproducible and clinically safe approaches for oral tissue repair
      and regeneration. Clearly, there is a convincing body of evidence which confirms
      the need for this type of treatment, and public health data worldwide indicates a
      more than adequate patient resource. The future of these therapies involving more
      biological approaches and the use of dental tissue stem cells is promising and
      advancing. Also there may be a significant interest of their application and
      wider potential to treat disorders beyond the craniofacial region. CLINICAL
      SIGNIFICANCE: Considering the interests of the patients who could possibly be
      helped by applying stem cell-based therapies should be carefully assessed against
      current ethical concerns regarding the moral status of the early embryo.

PMID- 24880032
TI  - Decrease in neuroimmune activation by HSV-mediated gene transfer of TNFalpha
      soluble receptor alleviates pain in rats with diabetic neuropathy.
AB  - The mechanisms of diabetic painful neuropathy are complicated and comprise of
      peripheral and central pathophysiological phenomena. A number of proinflammatory
      cytokines are involved in this process. Tumor necrosis factor alpha (TNF-alpha)
      is considered to be one of the major contributors of neuropathic pain. In order
      to explore the potential role of inflammation in the peripheral nervous system of
      Type 1 diabetic animals with painful neuropathy, we investigated whether TNF
      alpha is a key inflammatory mediator to the diabetic neuropathic pain and whether
      continuous delivery of TNFalpha soluble receptor from damaged axons achieved by
      HSV vector mediated transduction of DRG would block or alter the pain perception
      in animals with diabetic neuropathy. Diabetic animals exhibited changes in
      threshold of mechanical and thermal pain perception compared to control rats and
      also demonstrated increases in TNFalpha in the DRG, spinal cord dorsal horn,
      sciatic nerve and in the foot skin, 6 weeks after the onset of diabetes.
      Therapeutic approaches by HSV mediated expression of p55 TNF soluble receptor
      significantly attenuated the diabetes-induced hyperalgesia and decreased the
      expression of TNFalpha with reduction in the phosphorylation of p38MAPK in the
      spinal cord dorsal horn and DRG. The overall outcome of this study suggests that
      neuroinflammatory activation in the peripheral nervous system may be involved in
      the pathogenesis of painful neuropathy in Type 1 diabetes which can be alleviated
      by local expression of HSV vector expressing p55 TNF soluble receptor.

PMID- 24880039
TI  - Beneficial effects of Renin-Angiotensin system blockers on testicular
      steroidogenesis.
AB  - PURPOSE: We evaluated whether antihypertensive drugs that act through the renin
      angiotensin system would affect testis function. MATERIALS AND METHODS: Ten mice
      were fed standard chow and 40 received a high energy density diet. At 8 weeks the
      high energy density diet mice were divided into 4 groups of 10 each. The
      untreated group received the high energy density diet alone. The 3 treated groups
      received that diet plus aliskiren (50 mg/kg daily), enalapril (30 mg/kg daily)
      and losartan (10 mg/kg daily), respectively, for the next 6 weeks. Blood pressure
      was measured twice monthly. At the end of the treatment period all mice were
      sacrificed. One-way ANOVA and the Holm-Sidak post hoc test were used to analyze
      results. RESULTS: The high energy density diet led to a significant increase in
      blood pressure (p <0.05). All treatments resulted in normalized blood pressure.
      In regard to reproductive function, and serum testosterone and estradiol the gene
      and protein expression of StAR, aromatase and luteinizing hormone receptor, and
      the protein expression of angiotensin-converting enzyme, renin and angiotensin
      type 1 receptor blocker were significantly decreased by the high energy density
      diet. Of the treatments only enalapril reverted the changes. Also, angiotensin
      converting enzyme, angiotensin type 1 receptor blocker and renin protein
      expression were lower in all high energy density diet groups except the group
      that received enalapril. CONCLUSIONS: Only angiotensin-converting enzyme
      inhibitor reverted the hormonal and testis alterations caused by the high energy
      density diet. This suggests that enalapril should be the drug of choice for a
      patient who presents with previous reproductive dysfunction.

PMID- 24880040
TI  - Why is everyone so excited about thromboelastrography (TEG)?
AB  - Thromboelastrography (TEG) is one of the most common whole-blood viscoelastic
      coagulation tests used in clinical laboratories and at the point of care. TEG
      provides information on coagulation defects that are often difficult to detect
      using routine laboratory tests such as activated partial prothrombin time or
      prothrombin time. In certain critically ill patient populations, the use of TEG
      instead of or in addition to routine laboratory coagulation tests has been shown
      to improve outcomes or reduce transfusion requirements. However, TEG and other
      viscoelastic coagulation tests are affected by unique pre-analytic and analytic
      variables that do not impact other common laboratory coagulation tests. In this
      review the underlying principles, clinical applications, and laboratory aspects
      of TEG testing are discussed. 

PMID- 24880041
TI  - Anatomy of a value proposition for laboratory medicine.
AB  - Value is now becoming a key driver in the ongoing development of healthcare
      delivery; key facets include the identification of what is valuable and how that
      value can be identified, leveraged, and delivered. The concept of a value
      proposition is widely used in business but can be used in healthcare as a
      statement of the benefits, costs and value that an organization can deliver to
      its customers. The foundation of this statement in laboratory medicine is
      evidence of clinical and cost effectiveness, not only for the patient, but also
      for other stakeholders involved in the delivery of healthcare, e.g., the carer,
      service provider, commissioner, purchaser, and the supplier of the test or
      device, as well as society as a whole. However the value of any laboratory
      medicine investigation is only achieved if the output (the test result(s)), is
      acted upon by the initiator of the investigation. Laboratory medicine is one part
      of a complex intervention, and so the value proposition should encompass the
      breadth of that intervention - from addressing the unmet need through the
      generation of clinical, operational and economic outcomes. A value proposition in
      laboratory medicine is central to successful innovation and quality improvement
      in healthcare. 

PMID- 24880042
TI  - Quantitative proteomics reveals the link between minichromosome maintenance
      complex and glucose-induced proliferation of rat pancreatic INS-1E beta-cells.
AB  - Proper functioning of pancreatic beta-cells is a crucial for glucose homeostasis
      control, and therefore a main problem regarding type 2 diabetes onset and
      evolution. The ability of beta-cells to proliferate upon certain stimuli, such as
      elevated glucose concentration, is an essential property to overpass a major
      problem of the pathology: the decrease of beta-cell mass leading to a lack of
      insulin production. However, high glucose concentrations are also an inducer of
      beta-cell dysfunction, when proliferation become unable to overcome insulin
      demand. The control of beta-cell proliferation could represent an interesting
      target for the development of therapeutic molecules for type 2 diabetes
      treatment. To get new insights on beta-cell replication, we investigated the
      modulation of nuclear proteins of INS-1E cells submitted to medium and high
      glucose concentrations for 24h. Indeed, the nucleus should contain proteins
      responsible of proliferation-related events. The SILAC approach allowed us
      identifying 24 nuclear proteins whose expressions were modified by chronic high
      glucose. A wide Downstream Effects Analysis assigned the majority of the
      differentially expressed proteins to functions such as proliferation and cell
      cycle. Interestingly, our study linked for the first time the increase of
      expression of the 6 MCM components to glucose-induced stimulation in beta-cells.
      BIOLOGICAL SIGNIFICANCE: The current study represents a progress in the
      understanding of glucose-induced proliferation mechanisms in beta-cells. We
      applied the SILAC strategy to INS-1E cells cultivated with medium or high glucose
      concentrations for 24h, and we targeted nuclear proteins which have a central
      role in proliferation-related mechanisms. It allows quantifying 24 nuclear
      proteins, which are regulated by high glucose exposure. The vast majority of them
      are shown to be related to proliferation and cell cycle. We describe here for the
      first time than the 6 proteins of the MCM complex are involved in glucose
      mediated proliferation in beta-cells.

PMID- 24880045
TI  - Exploiting the temporal patterning of transient VEP signals: a statistical single
      trial methodology with implications to brain-computer interfaces (BCIs).
AB  - BACKGROUND: When visual evoked potentials (VEPs) are deployed in brain-computer
      interfaces (BCIs), the emphasis is put on stimulus design. In the case of
      transient VEPs (TVEPs) brain responses are never treated individually, i.e. on a
      single-trial (ST) basis, due to their poor signal quality. Therefore their main
      characteristic, which is the emergence during early latencies, remains
      unexplored. NEW METHOD: Following a pattern-analytic methodology, we investigated
      the possibility of using single-trial TVEP responses to differentiate between the
      different spatial locations where a particular visual stimulus appeared and
      decide whether it was attended or unattended by the subject. RESULTS: Covert
      spatial attention modulates the temporal patterning of TVEPs in such a way that a
      brief ST-segment, from a single synthesized sensor, is sufficient for a
      Mahalanobis-Taguchi (MT) system to decode subject's intention. COMPARISON WITH
      EXISTING METHOD(S): In contrast to previous VEP-based approaches, stimulus
      related information and user's intention are being decoded from transient ST
      signals via exploiting aspects of brain response in the temporal domain.
      CONCLUSIONS: We demonstrated that in the TVEP signals there is sufficient
      discriminative information, coming in the form of a temporal code. We were able
      to introduce an efficient scheme that can fully exploit this information for the
      benefit of online classification. The measured performance brings high
      expectations for incorporating these ideas in BCI-control.

PMID- 24880046
TI  - Unleashing the future potential of functional near-infrared spectroscopy in brain
      sciences.
AB  - The wondrous innovations bound to the introduction of functional near-infrared
      spectroscopy in cognitive neuroscience are characterized by a multifaceted
      nature, ranging from technological improvements to sophisticated signal
      processing methods; the outstanding progress enabled scientists to investigate a
      variety of hard-to-test clinical populations and to successfully employ optical
      imaging in fields that were almost unimaginable twenty years ago. Here we
      illustrate how the emerging use of fNIRS methodologies might represent a drawing
      power in a variety of challenging experimental and medical contexts; we expect in
      the near future a wide increase of the use of wireless fNIRS, especially in
      children and in particular clinical populations, as well as a striking progress
      of fNIRS-BCI and hybrid BCI systems for neurofeedback and neurorehabilitation.
      These emerging trends might dramatically foster the future potential of fNIRS in
      brain sciences, provided that they are properly supported by a significant
      progress in signal processing and cognitive neuroscience. 

PMID- 24880044
TI  - Microfluidic platform to evaluate migration of cells from patients with DYT1
      dystonia.
AB  - BACKGROUND: Microfluidic platforms for quantitative evaluation of cell biologic
      processes allow low cost and time efficient research studies of biological and
      pathological events, such as monitoring cell migration by real-time imaging. In
      healthy and disease states, cell migration is crucial in development and wound
      healing, as well as to maintain the body's homeostasis. NEW METHOD: The
      microfluidic chambers allow precise measurements to investigate whether
      fibroblasts carrying a mutation in the TOR1A gene, underlying the hereditary
      neurologic disease--DYT1 dystonia, have decreased migration properties when
      compared to control cells. RESULTS: We observed that fibroblasts from DYT1
      patients showed abnormalities in basic features of cell migration, such as
      reduced velocity and persistence of movement. COMPARISON WITH EXISTING METHOD:
      The microfluidic method enabled us to demonstrate reduced polarization of the
      nucleus and abnormal orientation of nuclei and Golgi inside the moving DYT1
      patient cells compared to control cells, as well as vectorial movement of single
      cells. CONCLUSION: We report here different assays useful in determining various
      parameters of cell migration in DYT1 patient cells as a consequence of the TOR1A
      gene mutation, including a microfluidic platform, which provides a means to
      evaluate real-time vectorial movement with single cell resolution in a three
      dimensional environment.

PMID- 24880043
TI  - Quantitative quadruple-label immunofluorescence of mitochondrial and cytoplasmic
      proteins in single neurons from human midbrain tissue.
AB  - BACKGROUND: Respiratory chain (RC) deficiencies are found in primary mtDNA
      diseases. Focal RC defects are also associated with ageing and neurodegenerative
      disorders, e.g. in substantia nigra (SN) neurons from Parkinson's disease
      patients. In mitochondrial disease and ageing, mtDNA mutational loads vary
      considerably between neurons necessitating single cell-based assessment of RC
      deficiencies. Evaluating the full extent of RC deficiency within SN neurons is
      challenging because their size precludes investigations in serial sections. We
      developed an assay to measure RC abnormalities in individual SN neurons using
      quadruple immunofluorescence. NEW METHOD: Using antibodies against subunits of
      complex I (CI) and IV, porin and tyrosine hydroxylase together with IgG subtype
      specific fluorescent labelled secondary antibodies, we quantified the expression
      of CI and CIV compared to mitochondrial mass in dopaminergic neurons. CI:porin
      and CIV:porin ratios were determined relative to a standard control. RESULTS:
      Quantification of expression of complex subunits in midbrain sections from
      patients with mtDNA disease and known RC deficiencies consistently showed reduced
      CI:porin and/or CIV:porin ratios. COMPARISON WITH EXISTING METHOD(S): The
      standard histochemical method to investigate mitochondrial dysfunction, the
      cytochrome c oxidase/succinate dehydrogenase assay, measures CIV and CII
      activities. To also study CI in a patient, immunohistology in additional
      sections, i.e. in different neurons, is required. Our method allows correlation
      of the expression of CI, CIV and mitochondrial mass at a single cell level.
      CONCLUSION: Quantitative quadruple-label immunofluorescence is a reliable tool to
      measure RC deficiencies in individual neurons that will enable new insights in
      the molecular mechanisms underlying inherited and acquired mitochondrial
      dysfunction.

PMID- 24880047
TI  - Identifying Purkinje cells using only their spontaneous simple spike activity.
AB  - BACKGROUND: We have extended our cerebellar cortical interneuron classification
      algorithm that uses statistics of spontaneous activity (Ruigrok et al., 2011) to
      include Purkinje cells. Purkinje cells were added because they do not always show
      a detectable complex spike, which is the accepted identification. The statistical
      measures used in the present study were obtained from morphologically identified
      interneurons and complex spike identified Purkinje cells, recorded from ketamine
      xylazine anesthetized rats and rabbits, and from awake rabbits. NEW METHOD: The
      new algorithm has an added decision step that classifies Purkinje cells using a
      combination of the median absolute difference from the median interspike interval
      (MAD) and the mean of the relative differences of successive interspike intervals
      (CV2). These measures reflect the high firing rate and intermediate regularity of
      Purkinje cell simple spike activity. RESULTS: Of 86 juxtacellularly labeled
      interneurons and 110 complex spike-identified Purkinje cells, 61 interneurons and
      95 Purkinje cells were correctly classified, 22 interneurons and 13 Purkinje
      cells were deemed unclassifiable, and 3 interneurons and 2 Purkinje cells were
      incorrectly classified. COMPARISON WITH EXISTING METHODS: The new algorithm
      improves on our previous algorithm because it includes Purkinje cells. This
      algorithm is the only one for the cerebellum that does not presume anatomical
      knowledge of whether the cells are in the molecular layer or the granular layer.
      CONCLUSIONS: These results strengthen the view that the new decision algorithm is
      useful for identifying neurons recorded at all cerebellar depths, particularly
      those neurons recorded in the rabbit vestibulocerebellum.

PMID- 24880048
TI  - Brain penetration assessment in vivo: a reliable and simple method in
      anesthetized rats at steady state.
AB  - BACKGROUND: For CNS drugs, brain disposition is of critical importance during
      drug discovery. In vitro methods are used early followed by more predictive in
      vivo methods later on in the drug discovery process. Current in vivo methods are
      costly, have long turnover times or do not measure brain disposition at steady
      state. NEW METHOD: A new method to evaluate drug brain disposition in vivo was
      developed in anaesthetized rats. Seven reference compounds were administered as
      an initial IV bolus (loading dose) followed by IV infusion for 4.5 h in order to
      obtain a steady state plasma concentration before brain sampling. The loading
      dose was estimated from a preliminary single dose IV pharmacokinetic study and
      was found to successfully bring plasma concentrations to steady state for
      compounds exhibiting either mono- or bi-compartmental pharmacokinetics. RESULTS:
      Using this method, a steady state lasting at least 2h was obtained, thus making
      the in vivo method robust with respect to differences in the pharmacokinetics
      and/or blood-to-brain equilibration rate of the compounds tested. The method
      produced highly reproducible results, with substantial advantages in terms of
      cost, turnaround time and animal welfare. COMPARISON WITH EXISTING METHODS: The
      results agreed with those reported in other, more elaborate preclinical models
      and in humans, enabling brain disposition to be assessed in a simple, efficient
      and robust in vivo model for new chemical entities. CONCLUSIONS: Introducing the
      presented method in drug discovery allows brain disposition to be assessed
      earlier in the drug discovery pipeline and thus facilitate the selection of
      potent and penetrant CNS drugs.

PMID- 24880049
TI  - Comparison of the effects of long-chain omega-3 fatty acid supplementation on
      plasma levels of free and esterified oxylipins.
AB  - INTRODUCTION: It is believed that many of the beneficial effects of long-chain
      omega-3 polyunsaturated fatty acids (LC n-3 PUFA) are mediated by their oxidized
      metabolites, the oxylipins. The formation and biological role of many cytochrome
      P450 and lipoxygenase derived hydroxy, epoxy and dihydroxy FA, particularly of
      oxylipins esterified in polar lipids and triglycerides remain unclear. In this
      study, we compared the impact of twelve weeks of LC n-3 PUFA supplementation on
      the patterns of free and total (sum of esterified and free) hydroxy, epoxy and
      dihydroxy FAs. SUBJECTS AND METHODS: Subjects (5 male; 5 female) between 46 and
      70 years were supplemented with 1.1g/d of eicosapentaenoic acid (EPA) and 0.74g/d
      docosahexaenoic acid (DHA) as ethyl esters. Blood samples were drawn before and
      after twelve weeks of treatment. Oxylipins in plasma were analyzed by LC-MS
      directly for free oxylipins and after saponification. Relative FA composition in
      erythrocyte membranes was analyzed by GC. RESULTS: LC n-3 PUFA treatment led to a
      significant increase in EPA (200%) and DHA (23%) in erythrocyte membranes. Of the
      oxylipins measured in plasma, total and free EPA-derived metabolites were highly
      increased (70-150%), while total AA-derived metabolites were decreased on average
      by 30%. There was no effect on DHA-metabolites. Concentrations of total hydroxy
      and epoxy FAs in plasma were considerably higher compared to free hydroxy and
      epoxy FAs (up to 350 times), while levels of most free dihydroxy FAs were in a
      similar range to total dihydroxy FAs. However, the individual ratios between
      total and free plasma oxylipins remained unchanged after LC n-3 PUFA treatment.
      DISCUSSION AND CONCLUSIONS: LC n-3 PUFA supplementation causes a shift in the
      levels of circulating oxylipins, having the strongest impact on EPA-derived
      epoxy, dihydroxy and hydroxy FA. The unchanged ratio of free and esterified
      oxylipins in plasma indicates that both concentrations are valuable biomarkers
      for assessing the individual status of these lipid mediators.

PMID- 24880050
TI  - Vasodilatory effect of 14,15-epoxyeicosatrienoic acid on mesenteric arteries in
      hypertensive and aged rats.
AB  - The objective of this study was to investigate the 14,15-epoxyeicosatrienoic acid
      (14,15-EET)-induced vasodilatations as well as the underlying signaling pathways
      in rat mesenteric arteries from young, adult and old normotensive (WKY) and
      hypertensive rats. Protein expressions for prostaglandin EP(1-4) receptors, large
      conductance Ca(2+)-activated K(+) (BK(Ca)) channels, and adenylate cyclase (AC)
      were determined together with 14,15-EET-induced vasodilatations in primary-
      versus secondary-branches of the mesenteric artery. Responses to 14,15-EET were
      greater in the smaller secondary- versus primary-branches (and also more
      sensitive with lower EC50) and were reduced in vessels from old (80 weeks) rats
      as well as from vessels from the spontaneous hypertensive rats (SHR). Regardless
      of age or hypertension responses to 14,15-EET were inhibited by the EP2
      antagonist AH6809, BK(Ca) channel inhibitor iberiotoxin, or 3',5'-cyclic
      monophosphate (cAMP)-protein kinase A (PKA) pathway antagonists. These data
      indicate 14,15-EET-induced vasodilatation is mediated via the activation of EP2
      receptors and opening of BK(Ca) channels. The expressions of the EP2 receptor and
      AC were markedly reduced in vessels from SHR as well as old rats, whereas BK(Ca)
      expression was reduced in old WKY and SHR, but not adult SHR. Furthermore,
      expression of the p53 protein, an indicator of cell senescence and apoptosis, was
      elevated in adult and old SHR as well as in old WKY. In summary, attenuated 14,15
      EET-induced vasodilatation in mesenteric arteries from old normotensive WKY as
      well as adult and old SHR is associated with reduced expression of EP2 receptors
      and AC.

PMID- 24880051
TI  - Processing of facial expressions in peripheral vision: neurophysiological
      evidence.
AB  - We investigated the time course and processes in the recognition of facial
      expressions in peripheral vision (10.5 degrees ). Happy faces were categorized
      more accurately and faster than angry, fearful, sad, and neutral faces.
      Consistently, the N1 (90 to 130ms post-stimulus) and N2pc (200-300ms) ERP (event
      related-potentials) components were more negative, and the SPWs (slow positive
      waves; 700-800ms) were smaller, for happy than for non-happy faces. Computational
      modeling revealed that the smiling mouth became visually salient earlier (95ms)
      than any other region, in temporal correspondence with the N1, thus showing an
      attentional capture by the smile. The N2pc presumably reflected the subsequent
      selective allocation of processing resources to happy faces. As a result, the
      reduced SPWs suggest that the decision process in expression categorization
      became less demanding for happy faces. We propose that facial expression
      recognition in peripheral vision is mainly driven by perceptual processing,
      without affective discrimination. 

PMID- 24880054
TI  - Recognition and repair of the slipped rectus muscle.
AB  - Since the first description of the slipped muscle as a complication of strabismus
      surgery in 1979, the distinctions between it and the lost muscle have become
      blurred both in the literature and in general understanding. Sixtytwo slipped
      muscles in 52 consecutive patients were reviewed in an effort to more fully
      describe this Important and often unrecognized entity. The range of clinical
      presentation of slipped muscle is large: from the immediate large postoperative
      over- or undercorrection with absent duction, to the gradual moderate deviation
      with subtly reduced excursion. The auctions provided by the slipped muscles
      ranged from complete absence to almost normal, with an average of 19 degrees 
      excursion beyond the midline. At surgery, recognizing the empty muscle capsule
      attached to the sclera with the tendon slipped posteriorly within it is
      imperative for its repair. Recognition is facilitated by suspecting it from
      clinical findings. Correction of the motility defect requires advancement of the
      muscle tissue and not just its empty capsule. Slippage can probably be prevented
      by using a surgical technique, which firmly locks the suture to the tendon and
      not just to the muscle capsule.

PMID- 24880052
TI  - Suberoylanilide hydroxamic acid radiosensitizes tumor hypoxic cells in vitro
      through the oxidation of nitroxyl to nitric oxide.
AB  - The pharmacological effects of hydroxamic acids are partially attributed to their
      ability to serve as HNO and/or NO donors under oxidative stress. Previously, it
      was concluded that oxidation of the histone deacetylase inhibitor suberoylanilide
      hydroxamic acid (SAHA) by the metmyoglobin/H2O2 reaction system releases NO,
      which was based on spin trapping of NO and accumulation of nitrite.
      Reinvestigation of this system demonstrates the accumulation of N2O, which is a
      marker of HNO formation, at similar rates under normoxia and anoxia. In addition,
      the yields of nitrite that accumulated in the absence and the presence of O2 did
      not differ, implying that the source of nitrite is other than autoxidation of NO.
      In this system metmyoglobin is instantaneously and continuously converted into
      compound II, leading to one-electron oxidation of SAHA to its respective
      transient nitroxide radical. Studies using pulse radiolysis show that one
      electron oxidation of SAHA (pKa=9.56 +/- 0.04) yields the respective nitroxide
      radical (pKa=9.1 +/- 0.2), which under all experimental conditions decomposes
      bimolecularly to yield HNO. The proposed mechanism suggests that compound I
      oxidizes SAHA to the respective nitroxide radical, which decomposes bimolecularly
      in competition with its oxidation by compound II to form HNO. Compound II also
      oxidizes HNO to NO and NO to nitrite. Given that NO, but not HNO, is an efficient
      hypoxic cell radiosensitizer, we hypothesized that under an oxidizing environment
      SAHA might act as a NO donor and radiosensitize hypoxic cells. Preincubation of
      A549 and HT29 cells with 2.5 MUM SAHA for 24h resulted in a sensitizer
      enhancement ratio at 0.01 survival levels (SER0.01) of 1.33 and 1.59,
      respectively. Preincubation of A549 cells with oxidized SAHA had hardly any
      effect and, with 2mM valproic acid, which lacks the hydroxamate group, resulted
      in SER0.01=1.17. Preincubation of HT29 cells with SAHA and Tempol, which readily
      oxidizes HNO to NO, enhanced the radiosensitizing effect of SAHA. Pretreatment
      with SAHA blocked A549 cells at the G1 stage of the cell cycle and upregulated
      gamma-H2AX after irradiation. Overall, we conclude that SAHA enhances tumor
      radioresponse by multiple mechanisms that might also involve its ability to serve
      as a NO donor under oxidizing environments.

PMID- 24880055
TI  - Introduction to special issue for men's health and laboratory medicine.

PMID- 24880056
TI  - Determinants of objectively measured physical functional performance in early to
      mid-stage Parkinson disease.
AB  - BACKGROUND: Parkinson disease (PD) may lead to functional limitations through
      both motor and nonmotor symptoms. Although patients with advanced disease have
      well-documented and profound functional limitations, less is known about the
      determinants of function in early to mid-stage disease where interventions may be
      more likely to benefit and preserve function. OBJECTIVE: The objective of the
      current study was to identify motor, cognitive, and gait determinants of physical
      functional performance in patients with early to mid-stage PD. DESIGN: This was a
      secondary analysis of cross-sectional baseline data from a randomized clinical
      trial of exercise. SETTING: The study was performed at a tertiary academic
      medical center. PARTICIPANTS: The study included 121 patients with early to mid
      stage PD. METHODS: Our functional performance outcomes included the following:
      the Continuous Scale Physical Functional Performance Test (CS-PFP; primary
      outcome); the Timed Up and Go test (TUG); and Section 2 (Activities of Daily
      Living) of the Unified Parkinson's Disease Rating Scale (UPDRS). Explanatory
      variables included measures of disease severity, motor function, cognitive
      function, balance, and gait. Stepwise linear regression models were used to
      determine correlations between explanatory variables and outcome measures.
      RESULTS: In our regression models, the CS-PFP significantly correlated with
      walking endurance (Six-Minute Walk Test; r(2) = 0.12, P < .0001), turning ability
      (360 degrees  Turn Test; r(2) = 0.03, P = .002), attention (Brief Test of
      Attention; r(2) = 0.01, P = .03), overall cognitive status (Mini-Mental State
      Examination; r(2) = 0.01, P = .04), and bradykinesia (timed tapping; r(2) = 0.02,
      P = .02). The TUG significantly correlated with walking speed (5-Meter Walk Test;
      r(2) = 0.33, P < .0001), stride length (r(2) = 0.25, P < .0001), turning ability
      (360 degrees  turn, r(2) = 0.05, P = .0003), and attention (r(2) = 0.016, P =
      .03). Section 2 of the UPDRS was significantly correlated with endurance (r(2) =
      0.09, P < .0001), turning ability (r(2) = 0.03, P = .001), and attention (r(2) =
      0.01, P = .03). CONCLUSIONS: Gait, motor, and cognitive function all contribute
      to objectively measured global functional ability in mild to moderate PD.
      Subjectively measured functional activity outcomes may underestimate the impact
      of both motor and nonmotor symptoms.

PMID- 24880057
TI  - Rehabilitation outcomes among burn injury patients with a second admission to an
      inpatient rehabilitation facility.
AB  - BACKGROUND: Burn survivors tend to have complex medical issues requiring
      rehabilitation to improve overall function and quality of life. A subset of burn
      patients treated in inpatient rehabilitation facilities (IRFs) may require more
      than 1 rehabilitation stay for the same injury. OBJECTIVE: To compare the
      rehabilitation outcomes among burn patients admitted to an IRF who were
      discharged to acute care and then readmitted to an IRF with burn patients
      admitted to an IRF only 1 time. DESIGN: Retrospective cohort study. SETTING:
      Inpatient rehabilitation facilities. PARTICIPANTS: Burn injury patients aged 18
      years or more who were admitted to IRFs between 2002 and 2011. METHODS: We
      performed a secondary analysis of data from Uniform Data System for Medical
      Rehabilitation, a national data repository. Outcomes of the repeaters' second
      stay (n = 188) were compared to the nonrepeaters' first and only stay (n =
      6,855), using linear regression and logistic regression to determine whether
      repeater status was associated with rehabilitation outcomes. MAIN OUTCOME
      MEASUREMENTS: Functional status (using the Functional Independence Measure [FIM]
      instrument) at admission, discharge and change, length of stay, FIM efficiency
      (total FIM points gained per day), and discharge disposition. RESULTS: Repeater
      status was inversely associated with discharge FIM total (coefficient = -3.42,
      95% confidence interval = -5.76, -1.07) and FIM change (coefficient = -4.05, 95%
      CI = -6.34, -1.75) in linear regression models. No other significant differences
      were found, and those differences in discharge FIM total and FIM change were
      small. CONCLUSIONS: Differences found in rehabilitation outcomes between the
      repeater and nonrepeater groups were small and may not reflect clinically
      meaningful differences. Burn injury patients who required a second IRF admission
      had rehabilitation outcomes similar to those of burn injury patients who did not
      require a second IRF admission, emphasizing the value of inpatient rehabilitation
      for burn injury IRF readmissions.

PMID- 24880058
TI  - Therapeutic synergism in the treatment of post-stroke arm paresis utilizing
      botulinum toxin, robotic therapy, and constraint-induced movement therapy.
AB  - Botulinum toxin type A (BtxA) injection, constraint-induced movement therapy
      (CIMT), and robotic therapy (RT) each represent promising approaches to enhance
      arm motor recovery after stroke. To provide more effective treatment for a 50
      year-old man with severe left spastic hemiparesis, we attempted to facilitate
      CIMT with adaptive approaches to extend the wrist and fingers using RT for 10
      consecutive weeks after BtxA injection. This combined treatment resulted in
      substantial improvements in arm function and the amount of arm use in activities
      of daily living, and may be effective for stroke patients with severe arm
      paresis. However, we were unable to sufficiently prove the efficacy of combined
      treatment based only on a single case. To fully elucidate the efficacy of the
      combined approach for patients with severe hemiparesis after stroke, future
      studies of a larger number of patients are needed. 

PMID- 24880059
TI  - Site-specific loading at the fifth metatarsal base in rehabilitative devices:
      implications for Jones fracture treatment.
AB  - BACKGROUND: Fractures of the fifth metatarsal base are a relatively common
      injury. Whether treated surgically or nonsurgically, injury rehabilitation
      typically involves immobilization in a rigid sandal or short controlled ankle
      movement (CAM) walker boot. OBJECTIVE: To determine the peak pressure, contact
      pressure, and impulse at the base of the fifth metatarsal in 3 common footwear
      devices during common gait activities. DESIGN: This was a retrospective
      comparative study. SETTING: Research was conducted in a sports performance
      laboratory at a university. PARTICIPANTS: Twenty subjects without a recent
      history of foot injuries volunteered to participate. METHODS: Each subject
      performed 3 common gait activities (walking, heel walking, and pivoting) in 3
      footwear devices (short CAM walker boot, postoperative sandal, running shoe).
      Pressure data were sampled (100 Hz) using individually sized plantar pressure
      insoles and software (Tekscan). Walking trials were collected at 1.0 m/s +/- 5%
      (FusionSport Timing Gates). OUTCOME MEASUREMENTS: Peak pressure, contact
      pressure, and impulse at the fifth metatarsal base region were determined for all
      trials for all subjects. Mixed-effect regression models were used to compare
      pairwise differences in outcome variables between footwear devices. RESULTS: The
      CAM walker boot resulted in significantly lower peak pressure at the fifth
      metatarsal during walking and heel-walking relative to the postoperative sandal
      (P < .01) and during heel-walking (P < .01) relative to the standard athletic
      shoe. The CAM walker boot significantly reduced contact pressures at the fifth
      metatarsal during walking and heel-walking relative to the postoperative sandal
      (P < .01), and during heel-walking relative to the standard athletic shoe (P <
      .001). CONCLUSIONS: Our results suggest that the short CAM walker boot more
      effectively offloads the fifth metatarsal during common gait activities than a
      postoperative sandal or a standard athletic shoe. A short CAM walker boot may be
      a beneficial rehabilitative tool for patients undergoing rehabilitation after
      treatment of Jones fractures and other base of fifth metatarsal fractures.

PMID- 24880061
TI  - Atypical presentation of popliteal artery entrapment syndrome: involvement of the
      anterior tibial artery.
AB  - Popliteal artery entrapment syndrome (PAES) is a rare condition that should be
      suspected in a young patient with exertional lower extremity pain. We report the
      case of an 18-year-old female volleyball player with bilateral exertional lower
      extremity pain who had been previously diagnosed with tendinitis and periostitis.
      Diagnostic studies showed entrapment of the left popliteal artery and the left
      anterior tibial artery. To our knowledge, there has only been 1 previous report
      of anterior tibial artery involvement in PAES. 

PMID- 24880060
TI  - Quality of life, shoulder range of motion, and spinal accessory nerve status in 5
      year survivors of head and neck cancer.
AB  - OBJECTIVE: To determine the association of neck dissection and radiation
      treatment for head and neck cancer (HNC) with subsequent shoulder range of motion
      (ROM) and quality of life (QOL) in 5-year survivors. DESIGN: A cross-sectional
      convenience sample. SETTING: Otolaryngology clinics at tertiary care hospital and
      Veterans Affairs medical center. PATIENTS: Five-year, disease-free survivors of
      HNC. METHODS: Demographic and cancer treatment information was collected,
      including type of neck dissection (none, spinal accessory "nerve sparing," and
      "nerve sacrificing") and radiation. QOL questionnaires were administered, and
      shoulder ROM was measured. MAIN OUTCOME MEASUREMENTS: University of Washington
      Quality of Life (UWQOL), Functional Assessment of Cancer Therapy (FACT) Head and
      Neck, and Performance Status Scale for Head and Neck. Shoulder ROM measurements
      included abduction, adduction, flexion, extension, internal and external
      rotation. RESULTS: One hundred and five survivors completed QOL surveys; 85
      survivors underwent additional shoulder ROM evaluations. The nerve sacrifice
      group exhibited significantly poorer scores for UWQOL measures of disfigurement,
      level of activity, recreation and/or entertainment, speech and shoulder
      disability, and willingness to eat in public, FACT functional well-being, and
      FACT Head and Neck (P < .05). Shoulder ROM for flexion and abduction was poorest
      in the nerve sacrifice group (P < .05). Radiation was associated with
      significantly worse UWQOL swallowing (P < .05), but no other differences were
      found for QOL or ROM measurements. Decreased QOL scores were associated with
      decreased shoulder flexion and abduction (P < .05). Survivors with decreased
      shoulder abduction had significantly (P < .05) worse scores in disfigurement,
      recreation and/or entertainment, employment, shoulder disability, and FACT
      emotional well-being. CONCLUSIONS: Sparing the spinal accessory nerve during neck
      dissection is associated with significantly less long-term shoulder disability in
      5-year survivors of HNC. QOL measures demonstrated the highest level of function
      in the no dissection group, an intermediate level of functioning with nerve
      sparing, and poorest function when the nerve is sacrificed. Decreased shoulder
      flexion and abduction is associated with reduced QOL in long-term survivors of
      HNC.

PMID- 24880062
TI  - Alpha2beta1 integrin promotes T cell survival and migration through the
      concomitant activation of ERK/Mcl-1 and p38 MAPK pathways.
AB  - Integrin-mediated attachment to extracellular matrix (ECM) is crucial for cancer
      progression. Malignant T cells such as acute lymphoblastic leukemia (T-ALL)
      express beta1 integrins, which mediate their interactions with ECM. However, the
      role of these interactions in T-ALL malignancy is still poorly explored. In the
      present study, we investigated the effect of collagen; an abundant ECM, on T-ALL
      survival and migration. We found that collagen through alpha2beta1 integrin
      promotes the survival of T-ALL cell lines in the absence of growth factors. T-ALL
      cell survival by collagen is associated with reduced caspase activation and
      maintenance of Mcl-1 levels. Collagen activated both ERK and p38 MAPKs but only
      MAPK/ERK was required for collagen-induced T-ALL survival. However, we found that
      alpha2beta1 integrin promoted T-ALL migration via both ERK and p38. Together
      these data indicate that alpha2beta1 integrin signaling can represent an
      important signaling pathway in T-ALL pathogenesis and suggest that its blockade
      could be beneficial in T-ALL treatment.

PMID- 24880064
TI  - Vav1 increases Bcl-2 expression by selective activation of Rac2-Akt in leukemia T
      cells.
AB  - Vav proteins are guanine nucleotide exchange factors (GEFs) that activate a group
      of small G proteins (GTPases). Vav1 is predominantly expressed in hematopoietic
      cells, whereas Vav2 and Vav3 are ubiquitously distributed in almost all human
      tissues. All three Vav proteins contain conserved structural motifs and associate
      with a variety of cellular activities including proliferation, migration, and
      survival. Previous observation with Jurkat leukemia T cells showed that Vav1
      possessed anti-apoptotic activity by enhancing Bcl-2 transcription. However the
      mechanism has not been unveiled. Here, we explored the effectors of Vav1 in
      promoting Bcl-2 expression in Jurkat cells and revealed that Rac2-Akt was
      specifically evoked by the expression of Vav1, but not Vav2 or Vav3. Although all
      three Vav isoforms existed in Jurkat cells, Rac2 was distinguishably activated by
      Vav1 and that led to enhanced Bcl-2 expression and cell survival. Akt was
      modulated downstream of Vav1-Rac2, and the activation of Akt was indispensable in
      the enhanced transcription of Bcl-2. Intriguingly, neither Vav2 nor Vav3 was able
      to activate Rac2-Akt pathway as determined by gene silencing approach. Our data
      illustrated a unique role of Vav1 in T leukemia survival by selectively
      triggering Rac2-Akt axis and elevating the expression of anti-apoptotic Bcl-2. 

PMID- 24880063
TI  - RhoA/ROCK downregulates FPR2-mediated NADPH oxidase activation in mouse bone
      marrow granulocytes.
AB  - Polymorphonuclear neutrophils (PMNs) express the high and low affinity receptors
      to formylated peptides (mFPR1 and mFPR2 in mice, accordingly). RhoA/ROCK (Rho
      activated kinase) pathway is crucial for cell motility and oxidase activity
      regulated via FPRs. There are contradictory data on RhoA-mediated regulation of
      NADPH oxidase activity in phagocytes. We have shown divergent Rho GTPases
      signaling via mFPR1 and mFPR2 to NADPH oxidase in PMNs from inflammatory site.
      The present study was aimed to find out the role of RhoA/ROCK in the respiratory
      burst activated via mFPR1 and mFPR2 in the bone marrow PMNs. Different kinetics
      of RhoA activation were detected with 0.1MUM fMLF and 1MUM WKYMVM operating via
      mFPR1 and mFPR2, accordingly. RhoA was translocated in fMLF-activated cells
      towards the cell center and juxtamembrane space versus uniform allocation in the
      resting cells. Specific inhibition of RhoA by CT04, Rho inhibitor I, weakly
      depressed the respiratory burst induced via mFPR1, but significantly increased
      the one induced via mFPR2. Inhibition of ROCK, the main effector of RhoA, by
      Y27632 led to the same effect on the respiratory burst. Regulation of mFPR2
      induced respiratory response by ROCK was impossible under the cytoskeleton
      disruption by cytochalasin D, whereas it persisted in the case of mFPR1
      activation. Thus we suggest RhoA to be one of the regulatory and signal
      transduction components in the respiratory burst through FPRs in the mouse bone
      marrow PMNs. Both mFPR1 and mFPR2 binding with a ligand trigger the activation of
      RhoA. FPR1 signaling through RhoA/ROCK increases NADPH-oxidase activity. But in
      FPR2 action RhoA/ROCK together with cytoskeleton-linked systems down-regulates
      NADPH-oxidase. This mechanism could restrain the reactive oxygen species
      dependent damage of own tissues during the chemotaxis of PMNs and in the resting
      cells.

PMID- 24880065
TI  - Development of a SYBR Green real-time RT-PCR assay for the detection of avian
      encephalomyelitis virus.
AB  - Avian encephalomyelitis virus (AEV) causes epidemic diseases in poultry
      worldwide. A SYBR Green real-time reverse transcription-polymerase chain reaction
      (rRT-PCR) assay was developed for the rapid detection and quantitation of AEV in
      this study. A pair of specific primers was designed in the highly conserved VP1
      gene of this virus. When comparing this assay with conventional RT-PCR, the rRT
      PCR assay was 100 times more sensitive and could detect levels as low as 10
      standard DNA copies of the AEV SX strain. The specificity of this technique was
      evaluated in five other avian pathogens. The AEV RNA was detected as early as
      three days post-infection in chicken embryos. All 18 clinical chicken brains
      collected from an AEV outbreak in Northwestern China were detected to be positive
      (100%) using the rRT-PCR assay. However, only 5 of the 18 samples were positive
      (28%) using the conventional RT-PCR. The results were confirmed by virus
      isolation in chicken embryos. This high sensitivity, specificity, and simplicity
      of the SYBR Green rRT-PCR approach can be a more effective method than the
      conventional one for AEV diagnosis and surveillance. 

PMID- 24880066
TI  - Prophylaxis and therapy of pandemic H1N1 virus infection using egg yolk antibody.
AB  - Influenza A virus infects the human respiratory system and causes acute and fatal
      pulmonary diseases. The emergence of drug-resistant viral strains highlights the
      need for alternative therapeutic approaches. In this work, IgY antibody was
      raised in immunized laying hens, and its antiviral activity was evaluated in the
      context of passive immunization. With inactivated whole H1N1 virus, high-titer
      IgY antibody 9.18 mg/mL egg yolk was induced by the eighth week after
      immunization. Western blotting and the hemagglutination inhibition (HI) test
      demonstrated that the IgY antibody could specifically bind the neuraminidase and
      hemagglutinin of the H1N1 virus. In the plaque reduction assay, the IgY antibody
      reduced the H1N1 viral infection in MDCK (Madin-Darby canine kidney) cells. In a
      mouse model, the anti-H1N1 IgY antibody exhibited in vivo protection by reducing
      the infectious titer of the virus in the lung while maintaining the weight and
      normal structure of the lung tissue. Additionally, the anti-H1N1 IgY antibody
      exhibited protective activity comparable to the neuraminidase inhibitor
      oseltamivir. These results demonstrated that IgY can be easily produced and can
      offers an effective alternative approach for influenza control.

PMID- 24880068
TI  - Comparison of ZetaPlus 60S and nitrocellulose membrane filters for the
      simultaneous concentration of F-RNA coliphages, porcine teschovirus and porcine
      adenovirus from river water.
AB  - Increasing attention is being paid to the impact of agricultural activities on
      water quality to understand the impact on public health. F-RNA coliphages have
      been proposed as viral indicators of fecal contamination while porcine
      teschovirus (PTV) and porcine adenovirus (PAdV) are proposed indicators of fecal
      contamination of swine origin. Viruses and coliphages are present in water in
      very low concentrations and must be concentrated to permit their detection. There
      is little information comparing the effectiveness of the methods for
      concentrating F-RNA coliphages with concentration methods for other viruses and
      vice versa. The objective of this study was to compare 5 current published
      methods for recovering F-RNA coliphages, PTV and PAdV from river water samples
      concentrated by electronegative nitrocellulose membrane filters (methods A and B)
      or electropositive Zeta Plus 60S filters (methods C-E). Method A is used
      routinely for the detection of coliphages (Mendez et al., 2004) and method C
      (Brassard et al., 2005) is the official method in Health Canada's compendium for
      the detection of viruses in bottled mineral or spring water. When river water was
      inoculated with stocks of F-RNA MS2, PAdV, and PTV to final concentrations of
      1*10(6) PFU/100 mL, 1*10(5) gc/100 mL and 3*10(5) gc/100 mL, respectively, a
      significantly higher recovery for each virus was consistently obtained for method
      A with recoveries of 52% for MS2, 95% for PAdV, and 1.5% for PTV. When method A
      was compared with method C for the detection of F-coliphages, PAdV and PTV in
      river water samples, viruses were detected with higher frequencies and at higher
      mean numbers with method A than with method C. With method A, F-coliphages were
      detected in 11/12 samples (5-154 PFU/100 mL), PTV in 12/12 samples (397-10,951
      gc/100 mL), PAdV in 1/12 samples (15 gc/100 mL), and F-RNA GIII in 1/12 samples
      (750 gc/100 mL) while F-RNA genotypes I, II, and IV were not detected by qRT-PCR.

PMID- 24880069
TI  - HPV integration detection in CaSki and SiHa using detection of integrated
      papillomavirus sequences and restriction-site PCR.
AB  - Human Papillomavirus (HPV) infection is the primary cause of cervical neoplasia.
      HPV DNA is integrated into the human genome in the majority of cervical cancers.
      The nature of integration may differ with integration incorporating a single copy
      of HPV or occurring in concatenated form. Our understanding of HPV tumorigenesis
      is largely based on studies using characterised cell lines with defined
      integration sites; these cell lines provide an invaluable standard for validation
      of diagnostic assays. Cell lines also further understanding of integration
      mechanisms in clinical samples. The objective of this study was to explore
      integration assays and to investigate integration events in cell lines where HPV
      is integrated in concatenated form. Restriction site PCR and detection of
      integrated papillomavirus sequences were performed on DNA from SiHa and CaSki. A
      novel integration site on Xq27.3 and HPV genome rearrangements were detected in
      CaSki DNA. However, where integration was previously detected by FISH in CaSki,
      and reported to be integrated in concatenated form, integration was not detected
      by DIPS or RS-PCR. The data presented illustrate that HPV copy number can hinder
      integration detection; this needs consideration when interpreting results from
      tests applied to clinical samples. 

PMID- 24880067
TI  - DNA vaccine encoding HPV-16 E7 with mutation in L-Y-C-Y-E pRb-binding motif
      induces potent anti-tumor responses in mice.
AB  - Cervical cancer is the second most common cancer among women worldwide and
      remains a clinical problem despite improvements in early detection and therapy.
      The human papillomavirus (HPV) type 16 (HPV16) E7 oncoprotein expressed in
      cervical carcinoma cells are considered as attractive tumor-specific antigen
      targets for immunotherapy. Since the transformation potential of the oncogenes,
      vaccination based of these oncogenes is not safe. In present study, DNA vaccine
      expressing the modified variant with mutation in pRb-binding motif of the HPV-16
      E7 oncoprotein was generated. A novel modified E7 gene with mutation in LYCYE
      motif was designed and constructed and the immunogenicity and antitumor effect of
      therapeutic DNA vaccines encoding the mutant and wild type of E7 gene were
      investigated. The L-Y-C-Y-E pRb-binding motif of E7 proteins has been involved in
      the immortalization and transformation of the host cell. The results showed that
      the mutant and wild type HPV-16 E7 vectors expressed the desired protein.
      Furthermore, the immunological mechanism behind mutant E7 DNA vaccine can be
      attributed at least partially to increased cytotoxic T lymphocyte, accompanied by
      the up-regulation of Th1-cytokine IFN-gamma and TNF-beta and down-regulation of
      Th3-cytokine TGF-beta. Immunized mice with mutant plasmid demonstrated
      significantly stronger cell immune responses and higher levels of tumor
      protection than wild-type E7 DNA vaccine. The results exhibit that modified E7
      DNA vaccine may be a promising candidate for development of therapeutic vaccine
      against HPV-16 cancers. 

PMID- 24880070
TI  - Identification and characterization of Highlands J virus from a Mississippi
      sandhill crane using unbiased next-generation sequencing.
AB  - Advances in massively parallel DNA sequencing platforms, commonly termed next
      generation sequencing (NGS) technologies, have greatly reduced time, labor, and
      cost associated with DNA sequencing. Thus, NGS has become a routine tool for new
      viral pathogen discovery and will likely become the standard for routine
      laboratory diagnostics of infectious diseases in the near future. This study
      demonstrated the application of NGS for the rapid identification and
      characterization of a virus isolated from the brain of an endangered Mississippi
      sandhill crane. This bird was part of a population restoration effort and was
      found in an emaciated state several days after Hurricane Isaac passed over the
      refuge in Mississippi in 2012. Post-mortem examination had identified
      trichostrongyliasis as the possible cause of death, but because a virus with
      morphology consistent with a togavirus was isolated from the brain of the bird,
      an arboviral etiology was strongly suspected. Because individual molecular assays
      for several known arboviruses were negative, unbiased NGS by Illumina MiSeq was
      used to definitively identify and characterize the causative viral agent. Whole
      genome sequencing and phylogenetic analysis revealed the viral isolate to be the
      Highlands J virus, a known avian pathogen. This study demonstrates the use of
      unbiased NGS for the rapid detection and characterization of an unidentified
      viral pathogen and the application of this technology to wildlife disease
      diagnostics and conservation medicine. 

PMID- 24880071
TI  - Development and evaluation of baculovirus-expressed Chikungunya virus E1 envelope
      proteins for serodiagnosis of Chikungunya infection.
AB  - Population-based serosurveillance studies provide critical estimates on community
      level immunity and the potential for future outbreaks. Currently, serological
      assays, such as IgG enzyme-linked immunosorbent assays (ELISAs) and indirect
      immunofluorescence tests (IIFT) based on the inactivated whole virus are used to
      determine past Chikungunya virus (CHIKV) infection. However, these commercially
      available tests have variable sensitivities. To develop and evaluate recombinant
      based CHIKV-specific IgG antibody capture ELISAs (GAC-ELISAs), baculoviruses
      carrying wild-type (E1-A226, named WT) or mutant (E1-A226V, named MUT) E1
      envelope protein genes of CHIKV were generated. The seroreactivity of recombinant
      CHIKV WT and MUT envelope proteins were determined using residual blood,
      collected from CHIKV-confirmed patients. The sensitivities of both recombinant
      CHIKV envelope proteins were 83.0% as measured by GAC-ELISAs. The specificities
      of both recombinant proteins were 87.8%. These GAC-ELISAs were also able to
      detect the persistence of anti-CHIKV IgG antibodies up to 6 months after the
      disease onset, together with rise in sensitivities with increasing time. These
      results suggest that the baculovirus purified recombinant CHIKV envelope proteins
      react with anti-CHIKV IgG antibodies and may be useful in population-based
      seroprevalence surveys. In addition, these GAC-ELISAs offer good diagnostic value
      to determine the recent/past CHIKV infection status in non-endemic populations. 

PMID- 24880072
TI  - Detection of avian influenza A/H7N9/2013 virus by real-time reverse transcription
      polymerase chain reaction.
AB  - The first case of avian influenza A/H7N9 infection was reported in Shanghai in
      mid-February, 2013; by May 1, 2013, it had infected 127 people and caused 26
      deaths in 10 provinces in China. Therefore, it is important to obtain reliable
      epidemiological data on the spread of this new infectious agent, a need that may
      be best met by the development of novel molecular methods. Here, a new method was
      described for the detection of avian influenza A/H7N9 using real-time reverse
      transcription-polymerase chain reaction (rRT-PCR). Using serial dilutions of
      avian influenza A H7N9 cultures, the detection limit of the assay was determined
      to be approximately 3.2*10(-4) HAUs (hemagglutination units) for the H7 gene and
      6.4*10(-4) HAUs for N9 gene. In tests of serial dilutions of in vitro-transcribed
      avian influenza A H7 and N9 gene RNA, positive results were obtained for target
      RNA containing at least three copies of the H7 gene and six copies of the N9
      gene. Thirteen throat swabs from H7N9 patients were tested; all tested positive
      in the assay. Specificity was evaluated by testing 18 other subtypes of influenza
      viruses; all tested negative. A total of 180 throat swabs from patients infected
      with influenza virus, including 60 from patients infected with seasonal influenza
      A/H1N1 virus, 60 from patients infected with pandemic influenza A/H1N1/2009
      virus, 30 from patients infected with seasonal influenza A/H3N2 virus and 30 from
      patients infected with influenza B virus, were also tested; all tested negative.

PMID- 24880073
TI  - The role of phosphatidylcholine and deoxycholic acid in inflammation.
AB  - AIMS: Phosphatidylcholine with deoxycholic acid (PC/DA) is widely used to reduce
      localized fat deposits with mild adverse effects. We previously demonstrated that
      PC induces lipolysis with mild PMN infiltration, while DA induces adipose tissue
      damage. Therefore, the aim of this study was to extend our understanding of the
      pro-inflammatory responses of PC, DA, and PC/DA. MAIN METHODS: We evaluated the
      level of edema and polymononuclear (PMN) infiltration by histopathological
      examination. Myeloperoxidase (MPO) activity was analyzed using an MPO activity
      assay kit. Levels of inflammatory cytokines (IL-1beta and IL-6) and PGE2 were
      measured by ELISA. KEY FINDINGS: A low and high dose of PC failed to induce an
      inflammatory response, whereas DA led to an intense inflammatory response in a
      dose dependent manner. Combined PC/DA treatment resulted in a mild inflammatory
      response that was notably less severe than higher DA. Together, these results
      demonstrated that DA plays a role in inflammation caused by combined PC/DA.
      Histopathological examination and measurement of MPO activity indicated that DA
      was the primary cause of edema and PMN infiltration. Further, increased levels of
      cytokines (IL-1beta and IL-6) and PGE2 demonstrated that DA might directly induce
      inflammation, whereas PC alone has no effect on inflammation. SIGNIFICANCE: These
      results indicate that DA rather than PC is responsible for inflammation, and that
      PC may not aggravate inflammatory responses induced by DA. Thus, the results of
      this study suggest that the adverse effects of PC/DA during localized fat
      treatment may be solely due to DA.

PMID- 24880074
TI  - Decursin attenuates hepatic fibrogenesis through interrupting TGF-beta-mediated
      NAD(P)H oxidase activation and Smad signaling in vivo and in vitro.
AB  - AIMS: We studied that a potent antifibrotic effect of decursin on in vivo liver
      damage model and the mechanism in inhibiting which transforming growth factor
      (TGF)-beta1-induced human hepatic stellate cells (HSCs) activation. MAIN METHODS:
      Liver injury was induced in vivo by intraperitoneal injection of carbon
      tetrachloride (CCl4) with or without decursin for 4weeks in mice. Human hepatic
      stellate cell line, an immortalized human HSC line, was used in in vitro assay
      system. The effects of decursin on HSC activation were measured by analyzing the
      expression of alpha-smooth muscle actin (alpha-SMA) and collagen I in liver
      tissue and human HSCs. KEY FINDINGS: Decursin treatment significantly reduced the
      ratio of liver/body weight, alpha-SMA activation, and type I collagen
      overexpression in CCl4 treated mice liver. The elevated serum levels, including
      ALT, AST, and ALP, were also decreased by decursin treatment. Treatment of
      decursin markedly proved the generation of reactive oxygen species, NAD(P)H
      oxidase (NOX) protein (1, 2, and 4) upregulation, NOX activity, and superoxide
      anion production in HSCs by TGF-beta1. It also significantly reduced TGF-beta1
      induced Smad 2/3 phosphorylation, nuclear translocation of Smad 4, and
      association of Smad 2/3-Smad 4 complex. Consistent with in vitro results,
      decursin treatment effectively blocked the levels of NOX protein, and Smad 2/3
      phosphorylation in injured mice liver. SIGNIFICANCE: Decursin blocked CCl4
      induced liver fibrosis and inhibited TGF-beta1-mediated HSC activation in vitro.
      These data demonstrated that decursin exhibited hepatoprotective effects on
      experimental fibrosis, potentially by inhibiting the TGF-beta1 induced NOX
      activation and Smad signaling.

PMID- 24880075
TI  - Effects of acute and sub-chronic L-dopa therapy on striatal L-dopa methylation
      and dopamine oxidation in an MPTP mouse model of Parkinsons disease.
AB  - AIMS: The molecular mechanisms for the loss of 3,4-dihydroxyphenylalanine (l
      dopa) efficacy during the treatment of Parkinson's disease (PD) are unknown.
      Modifications related to catecholamine metabolism such as changes in l-dopa and
      dopamine (DA) metabolism, the modulation of catecholamine enzymes and the
      production of interfering metabolites are the primary concerns of this study.
      MAIN METHODS: Normal (saline) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
      (MPTP) pre-treated mice were primed with 100mg/kg of l-dopa twice a day for 14
      days, and a matching group remained l-dopa naive. l-dopa naive and primed mice
      received a challenge dose of 100mg/kg of l-dopa and were sacrificed 30 min later.
      Striatal catecholamine levels and the expression and activity of catechol-O
      methyltransferase (COMT) were determined. KEY FINDINGS: Normal and MPTP pre
      treated animals metabolize l-dopa and DA similarly during l-dopa therapy.
      Administration of a challenge dose of l-dopa increased l-dopa and DA metabolism
      in l-dopa naive animals, and this effect was enhanced in l-dopa primed mice. The
      levels of 3-OMD in MPTP pre-treated animals were almost identical to those in
      normal mice, which we found are likely due to increased COMT activity in MPTP pre
      treated mice. SIGNIFICANCE: The results of this comparative study provide
      evidence that sub-chronic administration of l-dopa decreases the ability of the
      striatum to accumulate l-dopa and DA, due to increased metabolism via methylation
      and oxidation. This data supports evidence for the metabolic adaptation of the
      catecholamine pathway during long-term treatment with l-dopa, which may explain
      the causes for the loss of l-dopa efficacy.

PMID- 24880076
TI  - Emergence of OXA-48 carbapenemase-producing Enterobacter cloacae ST89 infection
      in Poland.
AB  - BACKGROUND: The utility of carbapenems, which are considered 'last-line' agents,
      is being diminished by the growing incidence of various resistance mechanisms in
      bacteria. We aimed to investigate the molecular mechanism of carbapenem
      resistance in Enterobacter cloacae recovered from a 76-year-old patient who had
      undergone coronary artery bypass grafting and repair of the mitral and tricuspid
      valves. Interestingly, the patient had no prior history of hospital admission
      abroad. METHODS: The Carba-NP test II and synergy testing were performed to
      confirm carbapenemase activity. PCR was used to detect carbapenemase-encoding
      genes. Nucleotide and amino acid sequence analysis was performed to identify OXA
      48 variants. Moreover, we performed multilocus sequence typing (MLST) of
      multidrug-resistant (MDR) E. cloacae. RESULTS: We detected no significant
      increase in zone diameter around disks with inhibitors. However, the Carba-NP
      test II revealed carbapenemase activity in all isolates. All isolates showed the
      presence of the exact OXA-48 carbapenemase variant. Furthermore, MLST analysis
      revealed that the MDR E. cloacae isolates belonged to ST89. CONCLUSIONS: We
      report a case of infection caused by a unique carbapenem-resistant E. cloacae
      ST89 producing OXA-48 carbapenemase. Interestingly, these pathogens developed
      resistance to other 'last-resort' agents, namely colistin and tigecycline. There
      is a crucial need for surveillance programs aimed at screening for carbapenemase
      producing Gram-negative bacteria, especially in patients transferred from high
      incidence areas.

PMID- 24880077
TI  - USA300-related methicillin-resistant Staphylococcus aureus clone is the
      predominant cause of community and hospital MRSA infections in Colombian
      children.
AB  - OBJECTIVE: Community-genotype methicillin-resistant Staphylococcus aureus (CG
      MRSA) isolates are known to be more virulent and clinically aggressive in
      children. The goal of the present study was characterize the molecular
      epidemiology of MRSA isolates causing infections in Colombian children. METHODS:
      An observational and prospective study was conducted between April 2009 and June
      2011 at 15 hospitals in Bogota, Colombia. A detailed epidemiological profile was
      made of 162 children infected with MRSA. The isolates were subjected to
      antimicrobial susceptibility testing, molecular characterization including 21
      virulence genes, SCCmec, spa and agr typing, multilocus sequence typing (MLST),
      and pulsed-field gel electrophoresis (PFGE). RESULTS: Among all isolates included
      in the study, 85.8% were obtained from patients whose infectious process was
      initiated in the community; of these, 69,8% occurred in patients without
      healthcare-associated risk factors. The molecular characterization of the
      isolates showed a high proportion (95.1%) containing a community-genotype profile
      with a high prevalence of SCCmec type IV, PVL-positives, and also related to CC8.
      Most CG-MRSA isolates (143, 92.9%) were genetically related to the pandemic clone
      USA300, differing by the presence of SCCmec IVc and the absence of the arginine
      catabolic mobile element (ACME). CONCLUSIONS: An increase in the frequency of CG
      MRSA infections has been reported worldwide. In this study we found that almost
      all MRSA infections in our pediatric population were caused by community-genotype
      isolates, supporting the success of the CG-MRSA clones.

PMID- 24880078
TI  - SOMCL-863, a novel, selective and orally bioavailable small-molecule c-Met
      inhibitor, exhibits antitumor activity both in vitro and in vivo.
AB  - Deregulation of HGF/c-Met signaling and its driven neoplastic phenotype are
      associated with a variety of human malignancies. We herein reported SOMCL-863 as
      a novel selective c-Met inhibitor which effectively abrogated c-Met signaling
      pathways, thereby leading to substantial impairment of c-Met-dependent cell
      proliferation, migration, invasion, cell scattering and invasive growth. In EBC-1
      and NCI-H1993 xenografts, SOMCL-863 exerted significant anti-tumor efficacy
      through anti-proliferative effects and antiangiogenic mechanisms, including
      reduction of tumor cell proliferation and reductions of microvessel density and
      secretion of proangiogenic factor IL-8. Together with the optimal pharmacokinetic
      properties, SOMCL-863 is a promising candidate worthy for further evaluation as a
      treatment of c-Met-driven human cancers. 

PMID- 24880080
TI  - SMYD2-dependent HSP90 methylation promotes cancer cell proliferation by
      regulating the chaperone complex formation.
AB  - Heat shock protein 90 (HSP90) is a highly conserved molecular chaperone that
      facilitates the maturation of a wide range of proteins, and it has been
      recognized as a crucial facilitator of oncogene addiction and cancer cell
      survival. Although HSP90 function is regulated by a variety of post-translational
      modifications, the physiological significance of methylation has not fully been
      elucidated. Here we demonstrate that HSP90AB1 is methylated by the histone
      methyltransferase SMYD2 and that it plays a critical role in human
      carcinogenesis. HSP90AB1 and SMYD2 can interact through the C-terminal region of
      HSP90AB1 and the SET domain of SMYD2. Both in vitro and in vivo methyltransferase
      assays revealed that SMYD2 could methylate HSP90AB1 and mass spectrometry
      analysis indicated lysines 531 and 574 of HSP90AB1 to be methylated. These
      methylation sites were shown to be important for the dimerization and chaperone
      complex formation of HSP90AB1. Furthermore, methylated HSP90AB1 accelerated the
      proliferation of cancer cells. Our study reveals a novel mechanism for human
      carcinogenesis via methylation of HSP90AB1 by SMYD2, and additional functional
      studies may assist in developing novel strategies for cancer therapy. 

PMID- 24880079
TI  - XMD8-92 inhibits pancreatic tumor xenograft growth via a DCLK1-dependent
      mechanism.
AB  - XMD8-92 is a kinase inhibitor with anti-cancer activity against lung and cervical
      cancers, but its effect on pancreatic ductal adenocarcinoma (PDAC) remains
      unknown. Doublecortin-like kinase1 (DCLK1) is upregulated in various cancers
      including PDAC. In this study, we showed that XMD8-92 inhibits AsPC-1 cancer cell
      proliferation and tumor xenograft growth. XMD8-92 treated tumors demonstrated
      significant downregulation of DCLK1 and several of its downstream targets
      (including c-MYC, KRAS, NOTCH1, ZEB1, ZEB2, SNAIL, SLUG, OCT4, SOX2, NANOG, KLF4,
      LIN28, VEGFR1, and VEGFR2) via upregulation of tumor suppressor miRNAs let-7a,
      miR-144, miR-200a-c, and miR-143/145; it did not however affect BMK1 downstream
      genes p21 and p53. These data taken together suggest that XMD8-92 treatment
      results in inhibition of DCLK1 and downstream oncogenic pathways (EMT,
      pluripotency, angiogenesis and anti-apoptotic), and is a promising
      chemotherapeutic agent against PDAC. 

PMID- 24880081
TI  - MHC-mismatched mice liver transplantation promotes tumor growth in liver graft.
AB  - Liver transplantation is a final therapeutic option for treatment of hepatic
      malignancies, but local recurrence remains high after surgery. However, the
      underlying mechanisms of local tumor recurrence are still unknown. We speculated
      that immunological status of transplanted liver may contribute to the progress of
      tumor development. CT-26 tumor cells are injected into graft after allogeneic or
      syngeneic liver transplantation. The growth pattern of tumor and the co
      relationship of regulatory T cell and effector T cells in liver graft were
      observed and investigated at 3d, 6d, 9d and 15d post-transplantation. The Hepatic
      Replacement Area of tumor in allogeneic grafts was significantly larger than that
      in syngeneic grafts. The activation of tumor growth in allografts was due to the
      dysfunction of effector T cells mediated by regulatory T cells in liver graft.
      Using nude mice model, we further confirmed that regulatory T cells from
      allograft significantly weaken the function of effector T cells in vivo. Our data
      has showed that MHC-mismatched mice liver transplantation can promote tumor
      growth in liver graft. For the first time, we demonstrated that susceptibility to
      tumor development in liver graft is due to the down-regulation of effector T
      cells' function mediated by the regulatory T cells.

PMID- 24880083
TI  - Cold-active antibacterial and antifungal activities and antibiotic resistance of
      bacteria isolated from an alpine hydrocarbon-contaminated industrial site.
AB  - Selection pressure in hydrocarbon-contaminated soils may lead not only to
      increased microbial resistance to antibiotics, but also to increased capacity of
      the soil indigenous population to produce antimicrobial compounds. Therefore, we
      studied the antibiotic resistance pattern and antibacterial and/or antifungal
      activities of 47 bacterial strains isolated from an industrial alpine site
      heavily polluted with petroleum hydrocarbons. Resistance to penicillin was more
      widespread (49%) than resistance to chloramphenicol or rifampicin (28%) or
      streptomycin (26%). Only 9% of the strains were resistant to tetracycline. The
      ability to produce cold-active (10  degrees C) antimicrobial compounds was tested
      by using human pathogenic bacteria (Escherichia coli, Shigella flexneri,
      Salmonella enterica, Pseudomonas aeruginosa, Staphylococcus aureus) and yeasts
      (Candida albicans, Cryptococcus neoformans) as indicator microorganisms. About
      two-thirds of the 47 tested strains produced compounds that inhibited growth of
      at least one indicator microorganism. Six strains inhibited growth of both
      bacteria and yeast indicators; 12 and 16 strains showed either antibacterial or
      antifungal activity, respectively. The most versatile bacteria with regard to
      multiple antibiotic resistance and antimicrobial activity belonged to
      Actinobacteria or Gammaproteobacteria. The antimicrobial compounds produced by
      three Pseudomonas spp. and two Serratia spp. strains were characterized in more
      detail by TLC and HPLC. Depending on the sensitivity of growth inhibition to
      enzymes, the compounds produced by the three pseudomonads contained a
      proteinaceous component.

PMID- 24880084
TI  - Ghrelin alters the stimulatory effect of cocaine on ethanol intake following
      mesolimbic or systemic administration.
AB  - Emerging evidence suggests that ghrelinergic and dopaminergic signaling interact
      in the neural control of motivation and ethanol reward. To further investigate a
      possible interaction between these two neurochemical systems, we examined the
      impact of ghrelin, cocaine and combined injections of ghrelin with cocaine, on
      voluntary ethanol intake. Male Sprague-Dawley rats were habituated to an 8%
      ethanol solution until intakes stabilized. Rats were then injected with ghrelin
      (2.5-10 nmol IP), cocaine (0.625-10 mg/kg IP) or ghrelin paired with cocaine. We
      also examined the impact of direct ghrelin (30-300 pmol) injections into the
      ventral tegmental area (VTA) co-administered with systemic cocaine. Ethanol
      consumption was measured at 2 and 6 h postinjection. While ghrelin and cocaine
      reliably increased ethanol intake, peripheral administration of the peptide
      elicited a dose-dependent differential effect on cocaine-induced intake.
      Pretreatment with ghrelin potentiated the effect of cocaine on ethanol intake at
      a low dose of 2.5 nmol, whereas 10 nmol suppressed cocaine-induced ethanol
      intake. This same 10 nmol dose was found to induce anxiogenic behavior as
      measured using an elevated plus maze paradigm. Finally, when injected directly
      into the VTA, ghrelin (300 pmol) potentiated the effect of systemic cocaine on
      ethanol intake. Combined subthreshold dosing of VTA ghrelin with a subthreshold
      dose of cocaine also evoked reliable increases in intake compared to vehicle.
      Overall, our data suggest that low doses of ghrelin elicit a stimulatory effect
      on cocaine-induced ethanol consummatory behavior and provide further support for
      an interactive role of dopaminergic and ghrelinergic transmission in ethanol
      reward. 

PMID- 24880086
TI  - The effects of betamethasone on allopregnanolone concentrations and brain
      development in preterm fetal sheep.
AB  - The risk of preterm delivery often means that the fetus will be exposed to
      exogenous synthetic glucocorticoids to accelerate fetal lung maturation, but
      effects on other organs, particularly the brain, are not understood. The
      neurosteroid allopregnanolone (AP) is a GABAA receptor agonist that influences
      fetal brain development and has neuroprotective properties. In this study we
      determined the impact of maternal glucocorticoid (betamethasone) administration
      on brain development and AP synthesis in preterm fetal sheep. Pregnant ewes
      underwent surgery at 105 days gestation for implantation of fetal catheters. Ewes
      received either betamethasone (BM; 11.4 mg; n=10) or vehicle (saline; n=5) by i.m
      injection on days five (BM1) and six (BM2) following surgery. Five fetuses of the
      BM treated ewes received an infusion of alfaxalone (20 mg) over 48 h commencing
      30 min prior to BM1. All animals were euthanased on day 7, and the fetal brains
      collected to determine AP concentrations and histopathology. BM significantly
      reduced AP levels in the fetal brain and placental cotyledons, and also in fetal
      plasma without altering progesterone concentrations. There was a significant
      decrease in the number of myelinating cells in subcortical white matter, but no
      change to total oligodendrocyte number. Co-administration of the AP analogue
      analog alfaxalone with BM prevented this change in MBP expression. BM, given at a
      dose clinically prescribed to accelerate lung maturation, adversely affects
      neurosteroid levels in the preterm fetal brain, and affects the maturational
      profile of white matter development; these effects were mitigated by the co
      administration of alfaxolone.

PMID- 24880085
TI  - (R)-[11C]PK11195 brain uptake as a biomarker of inflammation and antiepileptic
      drug resistance: evaluation in a rat epilepsy model.
AB  - Neuroinflammation has been suggested as a key determinant of the intrinsic
      severity of epilepsy. Glial cell activation and associated inflammatory signaling
      can influence seizure thresholds as well as the pharmacodynamics and
      pharmacokinetics of antiepileptic drugs. Based on these data, we hypothesized
      that molecular imaging of microglia activation might serve as a tool to predict
      drug refractoriness of epilepsy. Brain uptake of (R)-[11C]PK11195, a ligand of
      the translocator protein 18 kDa and molecular marker of microglia activation, was
      studied in a chronic model of temporal lobe epilepsy in rats with selection of
      phenobarbital responders and non-responders. In rats with drug-sensitive
      epilepsy, (R)-[11C]PK11195 brain uptake values were comparable to those in non
      epileptic controls. Analysis in non-responders revealed enhanced brain uptake of
      up to 39% in different brain regions. The difference might be related to the fact
      that non-responders exhibited higher baseline seizure frequencies than responders
      indicating a more pronounced intrinsic disease severity. In hippocampal sections,
      ED1 immunostaining argued against a general difference in microglia activation
      between both groups. Our data suggest that TSPO PET imaging might serve as a
      biomarker for drug resistance in temporal lobe epilepsy. However, it needs to be
      considered that our findings indicate that the TSPO PET data might merely reflect
      seizure frequency. Future experimental and clinical studies should further
      evaluate the validity of TSPO PET data to predict the response to phenobarbital
      and other antiepileptic drugs in longitudinal studies with scanning before drug
      exposure and with a focus on the early phase following an epileptogenic brain
      insult.

PMID- 24880088
TI  - Fluorescence as an alternative to light-scatter gating strategies to identify
      frozen-thawed cells with flow cytometry.
AB  - Flow cytometry is a key instrument in biological studies, used to identify and
      analyze cells in suspension. The identification of cells from debris is commonly
      based on light scatter properties as it has been shown that there is a
      relationship between forward scattered light and cell volume and this has become
      common practice in flow cytometry. Cryobiological conditions induce changes in
      cells that alter their light scatter properties. Cells with membrane damage from
      freeze-thaw stress produce lower forward scatter signals and may fall below
      standard forward scatter thresholds. In contrast to light scatter properties that
      cannot identify damaged cells from debris, fluorescent dyes used in membrane
      integrity and mitochondrial polarization assays are capable of labeling and
      discriminating all cells in suspension. Under cryobiological conditions,
      isolating cell populations is more effectively accomplished by gating on
      fluorescence rather than light scatter properties. This study shows the
      limitations of using forward scatter thresholds in flow cytometry to identify and
      gate cells after exposure to a freeze-thaw protocol and demonstrates the use of
      fluorescence as an alternative means of identifying and analyzing cells. 

PMID- 24880087
TI  - Temsirolimus attenuates tauopathy in vitro and in vivo by targeting tau
      hyperphosphorylation and autophagic clearance.
AB  - In a variety of neurodegenerative tauopathies including Alzheimer's disease,
      frontotemporal dementia and some types of Parkinson's disease, tau protein is
      abnormally hyperphosphorylated by several kinases and eventually aggregates to
      form neurofibrillary tangles, a neurotoxic pathological characteristic that
      closely correlates with cognitive impairments. Hence, targeting
      hyperphosphorylated tau protein has now been considered as a valid therapeutic
      approach for these neurodegenerative tauopathies. As a newly developed analog of
      rapamycin, temsirolimus was approved by the U.S. Food and Drug Administration and
      the European Medicines Agency for the treatment of renal cell carcinoma. Recent
      findings suggested that temsirolimus also provided beneficial effects in animal
      models of Huntington's disease and spinocerebellar ataxia type 3, two
      neurodegenerative diseases caused by accumulation of aberrant proteins within
      brain. To date, the therapeutic potentials of temsirolimus in neurodegenerative
      tauopathies have not been determined. Herein, we demonstrated for the first time
      that temsirolimus treatment effectively enhanced autophagic clearance of
      hyperphosphorylated tau in okadaic acid-incubated SH-SY5Y cells and in brain of
      P301S transgenic mice. Meanwhile, we showed that inactivation of glycogen
      synthase kinase-3beta, the most important tau kinase, might contribute to the
      temsirolimus-induced reduction of tau hyperphosphorylation in these two tauopathy
      models. More importantly, temsirolimus administration rescued spatial learning
      and memory impairments in P301S transgenic mice. These findings highlight
      temsirolimus administration as a potential therapeutic strategy for
      neurodegenerative tauopathies. 

PMID- 24880089
TI  - Phosphorylation mediated structural and functional changes in pentameric ligand
      gated ion channels: implications for drug discovery.
AB  - Pentameric ligand-gated ion channels (pLGICs) mediate numerous physiological
      processes, including fast neurotransmission in the brain. They are targeted by a
      large number of clinically-important drugs and disruptions to their function are
      associated with many neurological disorders. The phosphorylation of pLGICs can
      result in a wide range of functional consequences. Indeed, many neurological
      disorders result from pLGIC phosphorylation. For example, chronic pain is caused
      by the protein kinase A-mediated phosphorylation of alpha3 glycine receptors and
      nicotine addiction is mediated by the phosphorylation of alpha4- or alpha7
      containing nicotinic receptors. A recent study demonstrated that phosphorylation
      can induce a global conformational change in a pLGIC that propagates to the
      neurotransmitter-binding site. Here we present evidence that phosphorylation
      induced global conformational changes may be a universal phenomenon in pLGICs.
      This raises the possibility of designing drugs to specifically treat disease
      modified pLGICs. This review summarizes some of the opportunities available in
      this area. 

PMID- 24880090
TI  - Mitochondria express several nicotinic acetylcholine receptor subtypes to control
      various pathways of apoptosis induction.
AB  - Nicotinic acetylcholine receptors control survival, proliferation and cytokine
      release in non-excitable cells. Previously we reported that alpha7 nicotinic
      receptors were present in the outer membranes of mouse liver mitochondria to
      regulate mitochondrial pore formation and cytochrome c release. Here we used a
      wide spectrum of nicotinic receptor subunit-specific antibodies to show that
      mitochondria express several nicotinic receptor subtypes in a tissue-specific
      manner: brain and liver mitochondria contain alpha7beta2, alpha4beta2 and less
      alpha3beta2 nicotinic receptors, while mitochondria from the lung express
      preferentially alpha3beta4 receptor subtype; all of them are non-covalently
      connected to voltage-dependent anion channels and control cytochrome c release.
      By using selective ligands of different nicotinic receptor subtypes
      (acetylcholine (1 MUM) or dihydro-beta-erythroidine (1 MUM) for alpha4beta2),
      conotoxin MII (1 nM) for alpha3beta2, MLA (50 nM) for alpha7beta2 and
      acetylcholine (10 MUM) for all subtypes) and apoptogenic agents triggering
      different mitochondrial signaling pathways (1 MUM wortmannin, 90 MUM Ca(2+) or
      0.5 mM H2O2) it was found that alpha7beta2 receptors affect mainly PI3K/Akt
      pathway, while alpha3beta2 and alpha4beta2 nAChRs also significantly influence
      CaKMII- and Src-dependent pathways. It is concluded that cholinergic regulation
      in mitochondria is realized through multiple nicotinic receptor subtypes, which
      control various pathways inducing mitochondrial type of apoptosis.

PMID- 24880091
TI  - Extracellular-signal-regulated kinase 5 modulates the antioxidant response by
      transcriptionally controlling Sirtuin 1 expression in leukemic cells.
AB  - Cancer cell metabolism differs from that of non-transformed cells in the same
      tissue. This specific metabolism gives tumor cells growing advantages besides the
      effect in increasing anabolism. One of these advantages is immune evasion
      mediated by a lower expression of the mayor histocompatibility complex class I
      molecules. The extracellular-signal-regulated kinase-5 regulates both mayor
      histocompatibility complex class I expression and metabolic activity. However,
      the mechanisms underlying are largely unknown. We show here that extracellular
      signal-regulated kinase-5 regulates the transcription of the NADH(+)-dependent
      histone deacetylase silent mating type information regulation 2 homolog 1
      (Sirtuin 1) in leukemic Jurkat T cells. This involves the activation of the
      transcription factor myocyte enhancer factor-2 and its binding to the sirt1
      promoter. In addition, extracellular-signal-regulated kinase-5 is required for T
      cell receptor-induced and oxidative stress-induced full Sirtuin 1 expression.
      Extracellular-signal-regulated kinase-5 induces the expression of promoters
      containing the antioxidant response elements through a Sirtuin 1-dependent
      pathway. On the other hand, down modulation of extracellular-signal-regulated
      kinase-5 expression impairs the anti-oxidant response. Notably, the extracellular
      signal-regulated kinase-5 inhibitor BIX02189 induces apoptosis in acute myeloid
      leukemia tumor cells without affecting T cells from healthy donors. Our results
      unveil a new pathway that modulates metabolism in tumor cells. This pathway
      represents a promising therapeutic target in cancers with deep metabolic layouts
      such as acute myeloid leukemia. 

PMID- 24880092
TI  - Transient GFER knockdown in vivo impairs liver regeneration after partial
      hepatectomy.
AB  - BACKGROUND AND AIMS: Augmenter of Liver Regeneration is a protein encoded by the
      Growth Factor Erv1-Like gene. Its biological properties are crucial for cell
      survival since knock-out mice for Growth Factor Erv1-Like gene do not survive. In
      this study, we injected hepatotropic adenoviral particles harboring
      oligonucleotide sequences against Growth Factor Erv1-Like gene into 70% partially
      hepatectomized rats and studied the effect of gene silencing on the progression
      liver regeneration. METHODS: Partially hepatectomized rats were divided into
      three groups of animals and, before surgery, received either phosphate buffer
      saline, or adenoviral particles alone or adenoviral particles harboring the
      oligonucleotide silencing sequence. In each group, rats were sacrificed at 12, 24
      and 48 h after surgery. Liver tissues were collected to analyze the expression of
      Augmenter of Liver Regeneration, Bax, Bcl-2 and activated Caspase-9 and -3, as
      well as hepatocyte proliferation and apoptosis, polyamines levels and
      histological and ultrastructural features. RESULTS: Growth Factor Erv1-Like gene
      silencing reduced the compensatory hepatocellular proliferation triggered by
      surgery through (i) the reduction of polyamines synthesis, hepatocyte
      proliferation and anti-apoptotic gene expression and (ii) the increase of pro
      apoptotic gene expression and caspase activation. CONCLUSIONS: For the first
      time, using a technique of gene silencing in vivo, our results demonstrate that
      Growth Factor Erv1-Like gene knock-down, i.e., the lack of Augmenter of Liver
      Regeneration, modifies the expression of genes involved in cell apoptosis and
      inhibits early phase of DNA synthesis. As a consequence, a promotion of cell
      death and a reduction of cell proliferation occurs.

PMID- 24880093
TI  - Overexpression of SMARCE1 is associated with CD8+ T-cell infiltration in early
      stage ovarian cancer.
AB  - T-lymphocyte infiltration in ovarian tumors has been linked to a favorable
      prognosis, hence, exploring the mechanism of T-cell recruitment in the tumor is
      warranted. We employed a differential expression analysis to identify genes over
      expressed in early stage ovarian cancer samples that contained CD8 infiltrating T
      lymphocytes. Among other genes, we discovered that TTF1, a regulator of ribosomal
      RNA gene expression, and SMARCE1, a factor associated with chromatin remodeling
      were overexpressed in first stage CD8+ ovarian tumors. TTF1 and SMARCE1 mRNA
      levels showed a strong correlation with the number of intra-tumoral CD8+ cells in
      ovarian tumors. Interestingly, forced overexpression of SMARCE1 in SKOV3 ovarian
      cancer cells resulted in secretion of IL8, MIP1b and RANTES chemokines in the
      supernatant and triggered chemotaxis of CD8+ lymphocytes in a cell culture assay.
      The potency of SMARCE1-mediated chemotaxis appeared comparable to that caused by
      the transfection of the CXCL9 gene, coding for a chemokine known to attract T
      cells. Our analysis pinpoints TTF1 and SMARCE1 as genes potentially involved in
      cancer immunology. Since both TTF1 and SMARCE1 are involved in chromatin
      remodeling, our results imply an epigenetic regulatory mechanism for T-cell
      recruitment that invites deciphering. 

PMID- 24880094
TI  - Fibroblast growth factor 23 and Klotho serum levels in healthy children.
AB  - Data for fibroblast growth factor 23 (FGF23) and particularly for Klotho in
      healthy children are limited. We aimed to investigate the relationship between
      FGF23 and Klotho with age and TmP/GFR and to evaluate parameters that might
      affect FGF23 and Klotho. In 159 healthy children (82 boys) with a mean+/-SD age
      of 8.78+/-3.47years we measured FGF23 (intact FGF23/iFGF23 and C-terminal
      FGF23/cFGF23) and soluble aKlotho serum levels by ELISA. Mean+/-SD value for
      cFGF23, was 51.14+/-12.79 RU/ml whereas median (range) values for iFGF23 and
      Klotho were 35 (8.8, 120) pg/ml and 1945 (372, 5866) pg/ml respectively. Neither
      FGF23 nor Klotho were significantly associated with age. Pubertal children had
      higher Klotho than prepubertal (p<0.05), and girls had higher levels of cFGF23
      (p<0.05) and Klotho (p<0.001) than boys. Serum phosphate and TmP/GFR were
      positively associated with cFGF23 (p<0.01 and p<0.001), iFGF23 (p<0.05 and
      p<0.001) and Klotho (p<0.05 and p<0.01). Klotho was positively correlated with
      IGF-I (p<0.0001) and 1,25 (OH)2 vitamin D (p<0.05). In this study we provide data
      on cFGF23, iFGF23, and Klotho measured simultaneously in healthy children. The
      positive association of serum phosphate and TmP/GFR with FGF23 and Klotho
      suggests that they have a counterregulatory effect on phosphate homeostasis. The
      strong association of Klotho with IGF-I could indicate a role of Klotho in linear
      growth through phosphate regulation, but further studies are required. 

PMID- 24880096
TI  - Strabismus surgery is reconstructive surgery.

PMID- 24880095
TI  - The role of the collicular pathway in the salience-based progression of visual
      attention.
AB  - Visual attention has been shown to progress from the most to the least salient
      item in a given scene. Cognitive and physiological models assume that this
      orienting of covert attention relies on the collicular pathway, involving the
      superior colliculus and the pulvinar. Recent studies questioned this statement as
      they described attentional capture by visual items invisible to the superior
      colliculus. Electrophysiological studies shown that there is no direct
      projections from short-wave receptors to the superior colliculus. S-cone stimuli
      can thus be employed to assess visual processing without the involvement of the
      collicular pathway. We have attempted to investigate whether this pathway is
      involved in the salience-based orientation of attention by presenting S-cone
      stimuli. Volunteers were asked to make a judgment regarding a target among two
      distractors (all items of unequal sizes). Items' location and size varied
      randomly, as well as color, randomly black or calibrated for each subject to
      activate exclusively S-cones. The hierarchical pattern testifying of the salience
      based orientation of attention was only found with black stimuli, arguing in
      favor of an implication of the collicular pathway in salience. In a second
      experiment, one item was presented at a time in order to test the item
      multiplicity effect by comparing experiments. Performance was the most penalized
      when presenting multiple stimuli in the black condition. Results were interpreted
      in terms of distinct modes of processing by the collicular and geniculate
      pathways. The establishment of salience that determines attentional progression
      appeared to be only possible when the collicular pathway was solicited. 

PMID- 24880098
TI  - Down-regulation of GRP78 enhances apoptosis via CHOP pathway in retinal ischemia
      reperfusion injury.
AB  - Ischemia/reperfusion (I/R) injury is the main cause of retinal apoptosis. But the
      mechanism remains elusive. During I/R injury, the intracellular calcium levels
      increase, resulting in the generation of reactive oxygen species, which have been
      shown to cause endoplasmic reticulum (ER) stress. However, little is known about
      the correlation between apoptosis and ER stress in retinal I/R injury. In the
      present study, we demonstrated that ER stress was activated in the retina of rat
      I/R models. The transcriptional expression of ER stress-associated molecules,
      glucose-regulated protein-78 (GRP78) and C/EBP-homologous protein (CHOP) were
      significantly increased in I/R retinas in a time-dependent manner. Partial
      inhibition of the endogenous expression of GRP78 with antisense oligonucleotide
      resulted in significant retinal damage and apoptosis in I/R injury rats. Also,
      the transcriptional expression of CHOP was persistently increased. Our findings
      indicate that ER stress may play a critical role in I/R injury induced retinal
      damage, and GRP78 may exert anti-apoptotic actions in I/R retina. Importantly,
      the persistent high expression of CHOP might serve as a possible mechanism that
      contributes to the enhanced the I/R-induced apoptosis after GRP78 down
      regulation. These results may provide insight into the pathology of retinal I/R
      injury. 

PMID- 24880099
TI  - Food preference and intake in response to ambient odours in overweight and normal
      weight females.
AB  - In our food abundant environment, food cues play an important role in the
      regulation of energy intake. Odours can be considered as external cues that can
      signal energy content in the anticipatory phase of eating. This study aims to
      determine whether exposure to olfactory cues associated with energy dense foods
      leads to increased food intake and greater preference for energy-dense foods. In
      addition, we assessed whether BMI and hunger state modulated this effect. Twenty
      five overweight (mean BMI: 31.3 kg/m(2), S.E.: 0.6) and 25 normal-weight (mean
      BMI: 21.9 kg/m(2), S.E.: 0.4) females, matched on age and restraint score,
      participated. In 6 separate sessions they were exposed to odours of three
      different categories (signalling non-food, high-energy food and low-energy food)
      in two motivational states (hungry and satiated). After 10 min of exposure food
      preference was assessed with a computerized two-item forced choice task and after
      20 min a Bogus Taste Test was used to determine energy intake (kcal and g). In a
      hungry state, the participants ate more (p<.001) and preferred high-energy
      products significantly more often (p<.001) when compared to the satiated state. A
      trend finding for the interaction between hunger and BMI suggested that the food
      preference of overweight participants was less affected by their internal state
      (p=.068). Neither energy intake (kcal: p=.553; g: p=.683) nor food preference
      (p=.280) was influenced by ambient exposure to odours signalling different
      categories. Future studies need to explore whether food odours can indeed induce
      overeating. More insight is needed regarding the possible influence of context
      (e.g. short exposure duration, large variety of food) and personality traits
      (e.g. restraint, impulsive) on odour-induced overeating.

PMID- 24880100
TI  - Pharmacogenomics in pediatrics: personalized medicine showing eminent promise.

PMID- 24880101
TI  - What influences adolescents' contraceptive decision-making? A meta-ethnography.
AB  - Increased access to and use of contraception has contributed significantly to the
      decline in teen birth rates since 1991, yet many teens use contraception
      inconsistently or not at all. This meta-ethnography was conducted to identify the
      factors that influence adolescents' contraceptive decision-making. Fourteen
      qualitative studies were examined using G. W. Noblit and R. D. Hare's (1988) meta
      ethnographic approach. Three themes of self, partner and family were found to
      influence contraceptive decision-making in both positive and negative ways.
      Assisting adolescents to maximize positive and reduce negative influences
      regarding contraceptive decision-making has the potential to assist teens to more
      effectively avoid unintended pregnancy and sexually transmitted infections. 

PMID- 24880102
TI  - Reversal of target-specific oral anticoagulants.
AB  - Target-specific oral anticoagulants (TSOACs) provide safe and effective
      anticoagulation for the prevention and treatment of thrombosis in a variety of
      clinical settings by interfering with the activity of thrombin (dabigatran) or
      factor Xa (rivaroxaban, apixaban, edoxaban, betrixaban). Although TSOACs have
      practical advantages over vitamin K antagonists (VKAs), there are currently no
      antidotes to reverse their anticoagulant effect. Herein we summarize the
      available evidence for TSOAC reversal using nonspecific and specific reversal
      agents. We discuss important limitations of existing evidence, which is derived
      from studies in human volunteers, animal models and in vitro experiments. Studies
      evaluating the safety and efficacy of reversal agents on clinical outcomes such
      as bleeding and mortality in patients with TSOAC-associated bleeding are needed. 

PMID- 24880104
TI  - Cellular and molecular mechanisms of cartilage damage and repair.
AB  - Cartilage breakdown is the disabling outcome of rheumatic diseases, whether
      prevalently inflammatory such as rheumatoid arthritis or prevalently mechanical
      such as osteoarthritis (OA). Despite the differences between immune-mediated
      arthritides and OA, common mechanisms drive cartilage breakdown. Inflammation,
      chondrocyte phenotype and homeostatic mechanisms have recently been the focus of
      research and will be summarised in this review. 

PMID- 24880103
TI  - Peripheral and synovial mechanisms of humoral autoimmunity in rheumatoid
      arthritis.
AB  - One of the hallmarks of rheumatoid arthritis (RA) is the development of humoral
      autoimmunity resulting in circulating autoantibodies. The clinical efficacy of B
      cell-depleting biologic treatments highlighted a key role for autoreactive B cell
      activation in the pathogenesis of RA. In this review, we discuss the key
      mechanisms leading to breach of B cell self-tolerance in the peripheral
      compartment. We also highlight the contribution of synovial ectopic lymphoid
      structures (ELS) in the development of functional niches of autoreactive B cells
      promoting humoral autoimmunity in the inflamed RA joints over and above secondary
      lymphoid organs (SLO). 

PMID- 24880105
TI  - High-throughput epitope binning of therapeutic monoclonal antibodies: why you
      need to bin the fridge.
AB  - Analytical tools are evolving to meet the need for the higher-throughput
      characterization of therapeutic monoclonal antibodies. An antibody's epitope is
      arguably its most important property because it underpins its functional activity
      but, because epitope selection is innate, it remains an empirical process. Here,
      we focus on the emergence of label-free biosensors with throughput capabilities
      orders of magnitude higher than the previous state-of-the-art, which can
      facilitate large assays such as epitope binning so that they can be incorporated
      alongside functional activity screens, enabling the rapid identification of leads
      that exhibit unique and functional epitopes. In addition to streamlining the drug
      development process by saving time and cost, the information from epitope binning
      assays could provide the basis for intellectual property protection. 

PMID- 24880106
TI  - Targeting mitochondrial dysfunction as in aging and glaucoma.
AB  - Neurons depend on their mitochondria for optimum function and become susceptible
      with age. Mitochondrial function is gradually impaired during aging because more
      electrons are converted to reactive oxygen species rather than being converted to
      ATP. Retinal ganglion cell mitochondria are additionally affected in glaucoma
      because of reduced oxygen delivery. Thus, targeting neuronal mitochondria to
      enhance their function as in glaucoma and aspects associated with aging provides
      potential ways of attenuating degenerating diseases. A substance worthy of
      mention is rapamycin, which affects regulated in development and DNA damage 1
      (REDD1), and is known to enhance mitochondrial function. REDD1 appears to be
      prominent in retinal ganglion cells. An alternative exciting non-invasive
      approach is to use red light therapy that enhances mitochondrial function. 

PMID- 24880107
TI  - Epigenetic code and potential epigenetic-based therapies against chronic diseases
      in developmental origins.
AB  - Accumulated findings have demonstrated that the epigenetic code provides a
      potential link between prenatal stress and changes in gene expression that could
      be involved in the developmental programming of various chronic diseases in later
      life. Meanwhile, based on the fact that epigenetic modifications are reversible
      and can be manipulated, this provides a unique chance to develop multiple novel
      epigenetic-based therapeutic strategies against many chronic diseases in early
      developmental periods. This article will give a short review of recent findings
      of prenatal insult-induced epigenetic changes in developmental origins of several
      chronic diseases, and will attempt to provide an overview of the current
      epigenetic-based strategies applied in the early prevention, diagnosis and
      possible therapies for human chronic diseases. 

PMID- 24880108
TI  - Resolution of inflammation: examples of peptidergic players and pathways.
AB  - Appreciation for the resolution of inflammation has increased in recent years,
      with the detailing of specific mediators and pathways and the identification of
      (receptor) targets that could be exploited for innovative anti-inflammatory drug
      discovery programmes. Thus, acute inflammation resolves by the intervention of
      endogenous anti-inflammatory mediators that reduce white blood cell recruitment
      and promote removal of migrated leukocytes by apoptosis and phagocytosis by
      resident 'cleaners', such as the macrophages, resulting ultimately in the repair
      of the inflamed or injured tissue. Here, we explore a selection of pro-resolving
      proteinaceous mediators and targets, such as melanocortins and galectins. 

PMID- 24880109
TI  - An analysis of FDA-approved drugs for infectious disease: HIV/AIDS drugs.
AB  - HIV/AIDS is one of the worst pandemics in history. According to the World Health
      Organization, 26 million people have died since 1981 - 1.6 million in 2012 alone.
      The dramatic rise in HIV/AIDS mobilized a swift and impressive coordination among
      governmental, academic and private sector organizations to identify the virus and
      develop new treatments. Herein, we assess the arsenal of 28 new molecular
      entities (NMEs) targeting HIV/AIDS. These data demonstrate that the first
      approval of zidovudine presaged an expansion of the antiviral repertoire over the
      following years. Whereas the rate of HIV/AIDS NMEs is rapidly declining, so is
      the number of organizations developing NMEs. We speculate that decisions to
      abandon further research reflect, in part, growing costs and time required for
      development. 

PMID- 24880110
TI  - Ribosomal RNA and protein transcripts persist in the cysts of Entamoeba invadens.
AB  - In most organisms rDNA transcription ceases under conditions of growth stress.
      However, we have earlier shown that pre-rRNA accumulates during encystation in
      Entamoeba invadens. We labeled newly-synthesized rRNA during encystation, with
      [methyl-(3)H] methionine in the presence of chitinase to enable uptake of
      isotope. Incorporation rate reduced after 24h, and then increased to reach levels
      comparable with normal cells. The label was rapidly chased to the ribosomal
      pellet in dividing cells, while at late stages of encystation the ratio of counts
      going to the pellet dropped 3-fold. The transcript levels of selected ribosomal
      protein genes also went down initially but went up again at later stages of
      encystation. This suggested that rRNA and ribosomal protein transcription may be
      coordinately regulated. Our data shows that encysting E. invadens cells
      accumulate transcripts of both the RNA and protein components of the ribosome,
      which may ensure rapid synthesis of new ribosomes when growth resumes. 

PMID- 24880111
TI  - Raloxifene preserves phenytoin and sodium valproate induced bone loss by
      modulating serum estradiol and TGF-beta3 content in bone of female mice.
AB  - Antiepileptic drugs (AEDs)-induced adverse consequences on bone are now well
      recognized. Despite this, there is limited data on the effect of anti
      osteoporotic therapies on AEDs-induced bone loss. We hypothesize that estrogen
      deprivation following phenytoin (PHT) and sodium valproate (SVP) therapy could
      lead to adverse bony effects. Both PHT and SVP inhibit human aromatase enzyme and
      stimulate microsomal catabolism of oestrogens. Estrogen deficiency states are
      known to reduce the deposition of transforming growth factor-beta (TGF-beta3), a
      bone matrix protein, having anti-osteoclastic property. Thus, an attempt was made
      to investigate the effect of raloxifene, a selective oestrogen receptor
      modulator, in comparison with calcium and vitamin D3 (CVD) supplementation, on
      PHT and SVP-induced alterations in bone in mice and to unravel the role of
      estradiol and TGF-beta3 in mediation of bony effects by either AEDs or
      raloxifene. Further, the effect of raloxifene on seizures and on the
      antiepileptic efficacy of PHT and SVP was investigated. Swiss strains of female
      mice were treated with PHT (35 mg/kg, p.o.) and SVP (300 mg/kg, p.o.) for 120
      days to induce bone loss as evidenced by reduced bone mineral density (BMD) and
      altered bone turnover markers (BTMs) in lumbar bones (alkaline phosphatase,
      tartarate resistant acid phosphatase, hydroxyproline) and urine (calcium). The
      bone loss was accompanied by reduced serum estradiol levels and bone TGF-beta3
      content. Preventive and therapeutic treatment with raloxifene ameliorated bony
      alterations and was more effective than CVD. It also significantly restored
      estradiol and TGF-beta3 levels. Deprived estrogen levels (that in turn reduced
      lumbar TGF-beta3 content) following PHT and SVP, thus, might represent one of the
      various mechanisms of AEDs-induced bone loss. Raloxifene preserved the bony
      changes without interfering with antiepileptic efficacy of these drugs, and hence
      raloxifene could be a potential therapeutic option in the management of PHT and
      SVP-induced bone disease if clinically approved.

PMID- 24880112
TI  - Drug delivery: a process governed by species-specific lipophilicities.
AB  - Drug delivery is a cascade of molecular migration processes, in which the active
      principle dissolves in and partitions between several biological media of various
      hydrophilic and lipophilic character. Membrane penetration and other partitions
      are controlled by a number of physico-chemical parameters, the eminent ones are
      species-specific basicity and lipophilicity. Latter is a molecular property of
      immense importance in pharmacy, bio-, and medicinal chemistry, expressing the
      affinity of the molecule for a lipophilic environment. This review gives an
      overview of the types and definitions of the partition coefficient, the most
      widespread lipophilicity parameter, focusing on the species-specific
      (microscopic) partition coefficients. We survey the pertinent literature and
      summarize our recent works that enabled the determination of previously
      inaccessible species-specific partition coefficients for coexisting, inseparable
      protonation isomers too. This thorough insight provides explanation why some
      drugs unexpectedly get into the central nervous system and sheds some light on
      the submolecular mechanism of pharmacokinetic processes. The contribution of the
      various ionic forms to the overall partition can now be quantitated. As a result,
      there is clear-cut evidence that passive diffusion into lipophilic media is not
      necessarily predominated by the non-charged species, contrary to the widespread
      misbelief. 

PMID- 24880113
TI  - Nemo promotes Notch-mediated lateral inhibition downstream of proneural factors.
AB  - During neurogenesis, conserved tissue-specific proneural factors establish a
      cell's competence to take on neural fate from within a field of unspecified
      cells. Proneural genes encode basic helix-loop-helix transcription factors that
      promote the expression of 'core' and subtype-specific target genes. Target genes
      include both pan-neuronal genes and genes that aid in the process of refinement,
      known as lateral inhibition. In this process, proneural gene expression is
      increased in the neural progenitor while simultaneously down-regulated in the
      surrounding cells, in a Notch signalling-dependent manner. Here, we identify nemo
      (nmo) as a target of members of both Drosophila Atonal and Achaete-Scute
      proneural factor families and find that mammalian proneural homologs induce Nemo
      like-kinase (Nlk) expression in cell culture. We find that nmo loss of function
      leads to reduced expression of Notch targets and to perturbations in Notch
      mediated lateral inhibition. Furthermore, Notch hyperactivity can compensate for
      nmo loss in the Drosophila eye. Thus nmo promotes Notch-mediated lateral
      inhibition downstream of proneural factors during neurogenesis.

PMID- 24880114
TI  - Exuberant skin involvement in Systemic Lupus Erythematosus: a clinical case
      report.

PMID- 24880115
TI  - Time matters - acute stress response and glucocorticoid sensitivity in early
      multiple sclerosis.
AB  - OBJECTIVE: Psychosocial stress has frequently been associated with disease
      activity and acute exacerbations in multiple sclerosis (MS). Despite this well
      established finding, strikingly little is known about the acute hypothalamic
      pituitary-adrenal (HPA) and sympathetic-adrenal-medullary (SAM) stress response
      in MS. METHODS: Twenty-six early relapsing-remitting MS (RRMS) patients and
      seventeen age- and sex-matched healthy control subjects (CS) took part in the
      Trier Social Stress Test (TSST), a well validated psycho-social laboratory stress
      protocol. Repeated blood samples were analyzed for stress-related cortisol and
      catecholamine levels as well as for glucocorticoid sensitivity (GCS) of target
      immune cells. Chronic and acute stress appraisals were assessed by self-report
      measures. RESULTS: RRMS patients and CS did not differ in stress-related
      cortisol/catecholamine levels, GCS or stress appraisal in response to the TSST.
      However, cortisol release as well as GCS was strongly correlated with time since
      diagnosis but not with neurological disability. Patients with shorter disease
      duration (2-12 months) expressed a significantly higher cortisol stress response
      while MS patients with longer disease duration (14-36 months) showed a
      significantly diminished HPA response as well as lower post-stress GCS.
      DISCUSSION: There is evidence for a time-dependent variability in the HPA stress
      system with an increased cortisol stress response in the first year after
      diagnosis along with a more blunted HPA stress response and a diminished GCS in
      subsequent disease stages. Data underscore the highly dynamic nature of HPA axis
      regulation in the MS disease process, which could possibly relate to compensatory
      mechanisms within a cytokine-HPA axis feedback circuit model.

PMID- 24880116
TI  - Diffusion imaging in trigeminal neuralgia reveals abnormal trigeminal nerve and
      brain white matter.

PMID- 24880118
TI  - A conserved SUMOylation signaling for cell cycle control in a holocentric species
      Bombyx mori.
AB  - SUMOylation is an essential post-translational modification that regulates a
      variety of cellular processes including cell cycle progression. Although the
      SUMOylation pathway has been identified and investigated in many eukaryotes, the
      mechanisms of SUMOylation in regulating the functions of various substrates are
      still poorly understood. Here, we utilized a model species, the silkworm Bombyx
      mori that possesses holocentric chromosomes, to exploit the role of the
      SUMOylation system in cell cycle regulation. We identified all the components
      that are involved in the SUMOylation pathway in the silkworm genome. Our data
      revealed a cell cycle-dependent transcription of the SUMOylation genes,
      localization of the SUMOylation proteins, and abundance of the SUMOylation
      substrates in cultured silkworm cells. Importantly, the proliferation of the
      silkworm cells was strikingly inhibited by interference with SUMOylation genes
      expression, possibly due to an arrest of the SUMOylation-deficient cells at the
      G2/M phase. Furthermore, disruption of the SUMOylation genes induced the defects
      of holocentric chromosome congression and segregation during mitosis, which was
      consistent with high expressions of the SUMOylation genes and high enrichments of
      global SUMOylation at this stage, suggesting that the SUMOylation system in
      silkworm is essential for cell cycle regulation, with one particular role in
      mitosis. 

PMID- 24880119
TI  - Unexpected functional diversity in the fatty acid desaturases of the flour beetle
      Tribolium castaneum and identification of key residues determining activity.
AB  - Desaturases catalyse modifications to fatty acids which are essential to
      homeostasis and for pheromone and defensive chemical production. All desaturases
      of the flour beetle Tribolium castaneum were investigated via query of the
      sequenced genome which yielded 15 putative acyl-Coenzyme A genes. Eleven
      desaturase mRNA were obtained in full length and functionally expressed in yeast.
      Phylogenetic analysis separated the desaturases into 4 distinct clades; one clade
      contained conserved beetle Delta9 desaturases, second clade was Tribolium
      specific having diverse activities including Delta5, Delta9 and Delta12
      desaturation and the other 2 clades had mixed insect representatives. Three
      members of this clade contained unusual inserted sequences of ~20 residues in the
      C-terminal region and were related to desaturases that all contained similar
      inserts. Deletion of the entirety of the insert in the flour beetle Delta12
      desaturase abolished its activity but this was partially restored by the
      reintroduction of two histidine residues, suggesting the histidine(s) are
      required for activity but the full length insert is not. Five new desaturase
      activities were discovered: Delta9 desaturation of C12:0-C16:0 substrates; two
      unprecedented Delta5 enzymes acting on C18:0 and C16:0; Delta9 activity
      exclusively on C16:0 and a further stearate Delta9 desaturase. qPCR analysis
      ruled out a role in sex pheromone synthesis for the Delta5 and Delta9/C16:0
      desaturases. The flour beetle genome has underpinned an examination of all
      transcribed desaturases in the organism and revealed a diversity of novel and
      unusual activities, an improved understanding of the evolutionary relationships
      among insect desaturases and sequence determinants of activity. 

PMID- 24880120
TI  - The mitochondrial genome of the red alga Kappaphycus striatus ("Green Sacol"
      variety): complete nucleotide sequence, genome structure and organization, and
      comparative analysis.
AB  - The complete mitochondrial (mt) DNA sequence of the rhodophyte Kappaphycus
      striatus ("Green Sacol" variety) was determined. The mtDNA is circular, 25,242
      bases long (A+T content: 69.94%), and contains 50 densely packed genes comprising
      93.22% of the mitochondrial genome, with genes encoded on both strands. Through
      comparative analysis, the overall sequence, genome structure, and organization of
      K. striatus mtDNA were seen to be highly similar with other fully sequenced
      mitochondrial genomes of the class Florideophyceae. On the other hand, certain
      degrees of genome rearrangements and greater sequence dissimilarities were
      observed for the mtDNAs of other evolutionarily distant red algae, such as those
      from the class Bangiophyceae and Cyanidiophyceae, compared to that of K.
      striatus. Furthermore, a trend was observed wherein the red algal mtDNAs tend to
      encode lesser number of protein-coding genes, albeit not necessarily shorter, as
      the organism becomes more morphologically complex. This trend is supported by the
      phylogenetic tree inferred from the concatenated amino acid sequences of the
      deduced protein products of cytochrome c oxidase subunit genes (cox1, 2, and 3).

PMID- 24880121
TI  - Three novel degraded steroids from cultures of the Basidiomycete Antrodiella
      albocinnamomea.
AB  - Three novel degraded steroids, named albocisterols A-C (1-3), have been isolated
      from cultures of Antrodiella albocinnamomea. Their structures were defined by
      comprehensive spectroscopic analysis and single crystal X-ray crystallography.
      The mixture of compounds 2 and 3 exhibited significant inhibitory activities
      against protein tyrosine phosphatase 1B (PTP1B). 

PMID- 24880122
TI  - Differential response of C-type natriuretic peptide to estrogen and dexamethasone
      in adult bone.
AB  - C-type natriuretic peptide (CNP) is crucial in promoting endochondral bone growth
      in mammals including humans but whether this paracrine hormone participates in
      maintaining bone integrity in the mature skeleton is unknown. Accordingly we
      studied changes in plasma and bone tissue CNP in anoestrus adult ewes receiving
      short term anabolic (estrogen) or catabolic (dexamethasone) treatment for 7days.
      CNP and the aminoterminal fragment of the CNP prohormone (NTproCNP) were measured
      in plasma and extracts of cancellous bone excised from vertebral, iliac, tibial
      and marrow tissues. Concentrations of CNP peptides were much higher in vertebral
      and iliac extracts than those of tibial or marrow. Both plasma CNP and NTproCNP
      increased rapidly after estrogen followed by a later rise in bone alkaline
      phosphatase. Vertebral and iliac (but not tibial or marrow) CNP peptide content
      were significantly increased by estrogen. Consistent with a skeletal source,
      plasma NTproCNP was significantly associated with vertebral tissue CNP. In
      contrast, bone tissue CNP peptide content was unaffected by dexamethasone despite
      suppression of plasma CNP peptides and bone alkaline phosphatase. We postulate
      that increases in trabecular bone CNP reflect new endosteal bone formation in
      these estrogen responsive tissues whereas reduced plasma CNP peptides after
      dexamethasone, without change in cancellous bone content, reflects reductions in
      cortical bone turnover. 

PMID- 24880123
TI  - Precautions for examining infants at risk for hiv infection.

PMID- 24880124
TI  - High levels of the type III inorganic phosphate transporter PiT1 (SLC20A1) can
      confer faster cell adhesion.
AB  - The inorganic phosphate transporter PiT1 (SLC20A1) is ubiquitously expressed in
      mammalian cells. We recently showed that overexpression of human PiT1 was
      sufficient to increase proliferation of two strict density-inhibited cell lines,
      murine fibroblastic NIH3T3 and pre-osteoblastic MC3T3-E1 cells, and allowed the
      cultures to grow to higher cell densities. In addition, upon transformation
      NIH3T3 cells showed increased ability to form colonies in soft agar. The cellular
      regulation of PiT1 expression supports that cells utilize the PiT1 levels to
      control proliferation, with non-proliferating cells showing the lowest PiT1 mRNA
      levels. The mechanism behind the role of PiT1 in increased cell proliferation is
      not known. We, however, found that compared to control cells, cultures of NIH3T3
      cells overexpressing PiT1 upon seeding showed increased cell number after 24h and
      had shifted more cells from G0/G1 to S+G2/M within 12h, suggesting that an early
      event may play a role. We here show that expression of human PiT1 in NIH3T3 cells
      led to faster cell adhesion; this effect was not cell type specific in that it
      was also observed when expressing human PiT1 in MC3T3-E1 cells. We also show for
      NIH3T3 that PiT1 overexpression led to faster cell spreading. The final total
      numbers of attached cells did, however, not differ between cultures of PiT1
      overexpressing cells and control cells of neither cell type. We suggest that the
      PiT1-mediated fast adhesion potentials allow the cells to go faster out of G0/G1
      and thereby contribute to their proliferative advantage within the first 24h
      after seeding. 

PMID- 24880125
TI  - Degradation of AF1Q by chaperone-mediated autophagy.
AB  - AF1Q, a mixed lineage leukemia gene fusion partner, is identified as a poor
      prognostic biomarker for pediatric acute myeloid leukemia (AML), adult AML with
      normal cytogenetic and adult myelodysplastic syndrome. AF1Q is highly regulated
      during hematopoietic progenitor differentiation and development but its
      regulatory mechanism has not been defined clearly. In the present study, we used
      pharmacological and genetic approaches to influence chaperone-mediated autophagy
      (CMA) and explored the degradation mechanism of AF1Q. Pharmacological inhibitors
      of lysosomal degradation, such as chloroquine, increased AF1Q levels, whereas
      activators of CMA, including 6-aminonicotinamide and nutrient starvation,
      decreased AF1Q levels. AF1Q interacts with HSPA8 and LAMP-2A, which are core
      components of the CMA machinery. Knockdown of HSPA8 or LAMP-2A increased AF1Q
      protein levels, whereas overexpression showed the opposite effect. Using an amino
      acid deletion AF1Q mutation plasmid, we identified that AF1Q had a KFERQ-like
      motif which was recognized by HSPA8 for CMA-dependent proteolysis. In conclusion,
      we demonstrate for the first time that AF1Q can be degraded in lysosomes by CMA. 

PMID- 24880128
TI  - An automated method for the quantification of moving predators such as rotifers
      in biofilms by image analysis.
AB  - In natural environments as well as in industrial processes, microorganisms form
      biofilms. Eukaryotic microorganisms, like metazoans and protozoans, can shape the
      microbial communities because of their grazing activity. However, their influence
      on biofilm structure is often neglected because of the lack of appropriate
      methods to quantify their presence. In the present work, a method has been
      developed to quantify moving population of rotifers within a biofilm. We
      developed an automated approach to characterize the rotifer population density.
      Two time lapse images are recorded per biofilm location at an interval of 1s. By
      subtracting the two images from each other, rotifer displacements that occurred
      between the two images acquisition can be quantified. A comparison of the image
      analysis approach with manually counted rotifers showed a correlation of
      R(2)=0.90, validating the automated method. We verified our method with two
      biofilms of different superficial and community structures and measured rotifer
      densities of up to 1700 per cm(2). The method can be adapted for other types of
      moving organisms in biofilms like nematodes and ciliates. 

PMID- 24880129
TI  - Multispecies biofilm in an artificial wound bed--A novel model for in vitro
      assessment of solid antimicrobial dressings.
AB  - Wound infections represent a major problem, particularly in patients with chronic
      wounds. Bacteria in the wound exist mainly in the form of biofilms and are thus
      resistant to most antibiotics and antimicrobials. A simple and cost-effective in
      vitro model of chronic wound biofilms applied for testing treatments and solid
      devices, especially wound dressings, is presented in this work. The method is
      based on the well-established Lubbock chronic wound biofilm transferred onto an
      artificial agar wound bed. The biofilm formed by four bacterial species
      (Staphylococcus aureus, Enterococcus faecalis, Bacillus subtilis and Pseudomonas
      aeruginosa) was stable for up to 48h post-transplant. The applicability of the
      model was evaluated by testing two common iodine wound treatments. These
      observations indicate that this method enables assessing the effects of
      treatments on established resilient wound biofilms and is clinically highly
      relevant. 

PMID- 24880130
TI  - Development of an oriC vector for use in Mycoplasma synoviae.
AB  - Mycoplasma synoviae, an important poultry pathogen, belonging to the class
      Mollicutes, causes airsacculitis, synovitis, decreased egg production and
      produces significant economic losses. Efforts to determine M. synoviae virulence
      factors and their role in pathogenicity require suitable tools for genetic
      manipulation of this pathogen. This study describes, for the first time, the
      identification and cloning of the origin of replication (oriC) of M. synoviae to
      develop a replicable oriC vector for this mycoplasma. Shuttle vectors containing
      different putative oriC regions along with tetracycline resistance gene tetM were
      constructed to transform M. synoviae. An oriC vector, pMAS-LoriC, harbouring the
      complete dnaA gene along with upstream and downstream DnaA boxes, successfully
      transformed M. synoviae at an average transformation frequency of 1.07*10(-8)
      transformants per colony-forming unit (CFU), and remained freely replicating as
      well as integrated at the chromosomal oriC. Plasmid copy number for pMAS-LoriC
      was estimated to be 62+/-29 (average+/-SD) per cell. This study also provided
      evidence of the occurrence of homologous recombination and the functionality of
      the heterologous tetM determinant in M. synoviae. The transformation technique
      and the oriC vector developed in this study have the potential to be used in
      targeted gene disruption, gene complementation and expression studies in this
      organism. 

PMID- 24880131
TI  - Detection of stealthy small amphiphilic biomarkers.
AB  - Pathogen-specific biomarkers are secreted in the host during infection. Many
      important biomarkers are not proteins but rather small molecules that cannot be
      directly detected by conventional methods. However, these small molecule
      biomarkers, such as phenolic glycolipid-I (PGL-I) of Mycobacterium leprae and
      Mycobactin T (MbT) of Mycobacterium tuberculosis, are critical to the
      pathophysiology of infection, and may be important in the development of
      diagnostics, vaccines, and novel therapeutic strategies. Methods for the direct
      detection of these biomarkers may be of significance both for the diagnosis of
      infectious disease, and also for the laboratory study of such molecules. Herein,
      we present, for the first time, a transduction approach for the direct and rapid
      (30min) detection of small amphiphilic biomarkers in complex samples (e.g. serum)
      using a single affinity reagent. To our knowledge, this is the first
      demonstration of an assay for the direct detection of PGL-I, and the first single
      reporter assay for the detection of MbT. The assay format exploits the
      amphiphilic chemistry of the small molecule biomarkers, and is universally
      applicable to all amphiphiles. The assay is only the first step towards
      developing a robust system for the detection of amphiphilic biomarkers that are
      critical to infectious disease pathophysiology. 

PMID- 24880126
TI  - Heat shock protein 90beta stabilizes focal adhesion kinase and enhances cell
      migration and invasion in breast cancer cells.
AB  - Focal adhesion kinase (FAK) acts as a regulator of cellular signaling and may
      promote cell spreading, motility, invasion and survival in malignancy. Elevated
      expression and activity of FAK frequently correlate with tumor cell metastasis
      and poor prognosis in breast cancer. However, the mechanisms by which the
      turnover of FAK is regulated remain elusive. Here we report that heat shock
      protein 90beta (HSP90beta) interacts with FAK and the middle domain (amino acids
      233-620) of HSP90beta is mainly responsible for this interaction. Furthermore, we
      found that HSP90beta regulates FAK stability since HSP90beta inhibitor 17-AAG
      triggers FAK ubiquitylation and subsequent proteasome-dependent degradation.
      Moreover, disrupted FAK-HSP90beta interaction induced by 17-AAG contributes to
      attenuation of tumor cell growth, migration, and invasion. Together, our results
      reveal how HSP90beta regulates FAK stability and identifies a potential
      therapeutic strategy to breast cancer. 

PMID- 24880132
TI  - Extensor hood injuries: a rare ultrasound finding in our patient's hands.

PMID- 24880133
TI  - Decoding fingertip trajectory from electrocorticographic signals in humans.
AB  - Seeking to apply brain-machine interface technology in neuroprosthetics, a number
      of methods for predicting trajectory of the elbow and wrist have been proposed
      and have shown remarkable results. Recently, the prediction of hand trajectory
      and classification of hand gestures or grasping types have attracted considerable
      attention. However, trajectory prediction for precise finger motion has remained
      a challenge. We proposed a method for the prediction of fingertip motions from
      electrocorticographic signals in human cortex. A patient performed
      extension/flexion tasks with three fingers. Average Pearson's correlation
      coefficients and normalized root-mean-square errors between decoded and actual
      trajectories were 0.83-0.90 and 0.24-0.48, respectively. To confirm
      generalizability to other users, we applied our method to the BCI Competition IV
      open data sets. Our method showed that the prediction accuracy of fingertip
      trajectory could be equivalent to that of other results in the competition. 

PMID- 24880135
TI  - The driver and passenger effects of isocitrate dehydrogenase 1 and 2 mutations in
      oncogenesis and survival prolongation.
AB  - Mutations in isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) are key events in
      the development of glioma, acute myeloid leukemia (AML), chondrosarcoma,
      intrahepatic cholangiocarcinoma (ICC), and angioimmunoblastic T-cell lymphoma.
      They also cause D-2-hydroxyglutaric aciduria and Ollier and Maffucci syndromes.
      IDH1/2 mutations are associated with prolonged survival in glioma and in ICC, but
      not in AML. The reason for this is unknown. In their wild-type forms, IDH1 and
      IDH2 convert isocitrate and NADP(+) to alpha-ketoglutarate (alphaKG) and NADPH.
      Missense mutations in the active sites of these enzymes induce a neo-enzymatic
      reaction wherein NADPH reduces alphaKG to D-2-hydroxyglutarate (D-2HG). The
      resulting D-2HG accumulation leads to hypoxia-inducible factor 1alpha
      degradation, and changes in epigenetics and extracellular matrix homeostasis.
      Such mutations also imply less NADPH production capacity. Each of these effects
      could play a role in cancer formation. Here, we provide an overview of the
      literature and discuss which downstream molecular effects are likely to be the
      drivers of the oncogenic and survival-prolonging properties of IDH1/2 mutations.
      We discuss interactions between mutant IDH1/2 inhibitors and conventional
      therapies. Understanding of the biochemical consequences of IDH1/2 mutations in
      oncogenesis and survival prolongation will yield valuable information for
      rational therapy design: it will tell us which oncogenic processes should be
      blocked and which "survivalogenic" effects should be retained. 

PMID- 24880137
TI  - Microcystin accumulation in cladocerans: first evidence of MC uptake from aqueous
      extracts of a natural bloom sample.
AB  - Bioaccumulation of microcystins (MC) in zooplankton has been shown in several
      studies, mainly in field samples. A few studies, however, have demonstrated MC
      bioaccumulation in laboratory experiments. Although ingestion of cell-bound MC is
      considered the main route of MC accumulation, another important source is the MC
      from the dissolved fraction (DMC). This study reports the accumulation of DMC
      from aqueous extracts of natural bloom samples in three cladoceran species: Moina
      micrura, Daphnia laevis and Daphnia similis. Animals were exposed for 96 h to
      aqueous extracts of lyophilized matter from two bloom samples from Colombian
      reservoirs in different concentrations (25-1000 mg DW L(-1)). Analysis by HPLC-MS
      detected MC-LR in these samples at concentrations of 434-538 MUg g(-1). For the
      analysis of MC in animal tissues the samples were homogenized and sonicated in
      methanol:water (75%) and analyzed by ELISA. Results showed that the animals
      uptake of MC increased with increasing exposure concentrations of aqueous
      extracts, with M. micrura and D. laevis clones presenting the highest MC
      concentrations in their tissues (up to 1170-1260 MUg g(-1)) while D. similis the
      lowest (184 MUg g(-1)). This study shows, for the first time, that MC uptake from
      dissolved fraction by zooplankton is possible, not only from the ingestion of
      seston or cell-bound MC as previously demonstrated. 

PMID- 24880136
TI  - Urinary metabolomic fingerprinting after consumption of a probiotic strain in
      women with mastitis.
AB  - Infectious mastitis is a common condition among lactating women, with
      staphylococci and streptococci being the main aetiological agents. In this
      context, some lactobacilli strains isolated from breast milk appear to be
      particularly effective for treating mastitis and, therefore, constitute an
      attractive alternative to antibiotherapy. A (1)H NMR-based metabolomic approach
      was applied to detect metabolomic differences after consuming a probiotic strain
      (Lactobacillus salivarius PS2) in women with mastitis. 24h urine of women with
      lactational mastitis was collected at baseline and after 21 days of probiotic
      (PB) administration. Multivariate analysis (OSC-PLS-DA and hierarchical
      clustering) showed metabolome differences after PB treatment. The discriminant
      metabolites detected at baseline were lactose, and ibuprofen and acetaminophen
      (two pharmacological drugs commonly used for mastitis pain), while, after PB
      intake, creatine and the gut microbial co-metabolites hippurate and TMAO were
      detected. In addition, a voluntary desertion of the pharmacological drugs
      ibuprofen and acetaminophen was observed after probiotic administration. The
      application of NMR-based metabolomics enabled the identification of the overall
      effects of probiotic consumption among women suffering from mastitis and
      highlighted the potential of this approach in evaluating the outcomes of
      probiotics consumption. To our knowledge, this is the first time that this
      approach has been applied in women with mastitis during lactation. 

PMID- 24880140
TI  - A challenging case of diffuse diabetic musculoskeletal system involvement:
      diagnostic confusion with rheumatoid arthritis.
AB  - A diabetic patient who was misdiagnosed as rheumatoid arthritis because of
      complicated musculoskeletal manifestations of diabetes is reported here. A 57
      year old woman had been on sulphasalazine treatment with a diagnosis of
      rheumatoid arthritis for 3 years but failed to respond. Her past medical history
      disclosed that she had been using metformin due to diabetes mellitus for 8 years.
      On physical examination there was no evidence of arthritis. Her clinical picture
      was compatible with diffuse idiopathic skeletal hyperostosis (DISH), shoulder
      periarthritis, carpal tunnel syndrome, limited joint mobility of diabetes and
      furthermore myalgia due to metformin induced by hypovitaminosis D. Finally
      rheumatoid arthritis was excluded and a diagnosis of diabetes mellitus originated
      diffuse musculoskeletal system involvement was made. Diabetic musculoskeletal
      complications are common and sometimes cause clinical dilemmas. This case is also
      important for highlighting the contribution of low vitamin D status to the
      clinical status.

PMID- 24880142
TI  - Corneal epithelial and neuronal interactions: role in wound healing.
AB  - Impaired corneal innervation and sensitivity are the main causes of corneal
      neurotrophic keratopathy which simultaneously also leads to poor epithelial wound
      healing. Restoration of the diminished communication between the corneal
      epithelium and trigeminal nerve is indispensable for the proper functioning of
      the epithelium. The present study aims to investigate corneal epithelial and
      trigeminal neuron interactions to shed light on corneal wound healing during
      neurotrophic keratopathy. Mouse trigeminal neurons and corneal epithelial cells
      were cultured according to standard methods. To study the effect of corneal
      epithelial cells on trigeminal neurons as well as the effect of trigeminal
      neurons on corneal epithelial cells during wound healing, conditioned media from
      the cultures of pure trigeminal neurons (CNM) and corneal epithelial cells (CEM)
      were collected freshly and applied on the other cell type. Neurite outgrowth
      assay and RT-PCR analysis using primers specific for substance P (SP), Map1a,
      Map1b were performed on trigeminal neurons in the presence of CEM. We observed an
      increase in the neurite outgrowth in the presence of CEM and also in co-culture
      with corneal epithelial cells. Increase in the expression of SP mRNA and a
      decrease in the expression of Map1b mRNA was observed in the presence of CEM. We
      also observed the presence of epithelial-to-mesenchymal transition (EMT)-like
      phenomenon during wound healing using a scratch assay in primary corneal
      epithelial cultures. This system was further employed to study the effect of CNM
      on corneal epithelial cells in the context of wound healing to find the effect of
      trigeminal neurons on epithelial cells. RT-PCR analysis of Pax6 expression in
      corneal epithelial cell cultures with scratch served as a positive control.
      Further, we also show the expression of bone morphogenetic protein 7 (BMP7) mRNA
      in corneal epithelial cells which is decreased gradually along with Pax6 mRNA
      when cultured together in the presence of CNM. The expression and down regulation
      of BMP7 in the presence of CNM was further confirmed at the protein level by
      western blotting. From this study it seems that the epithelial and neuronal
      interactions in the cornea may contribute to the corneal innervation as well as
      recovery of corneal epithelial cells during injury. Appraising the differences in
      the expression of various signalling molecules during EMT of epithelial cells in
      the presence of SP and BMP7 gives an insight into the detailed dissection of the
      involved signalling pathways to develop future therapeutics. 

PMID- 24880141
TI  - Simvastatin, an HMG-CoA reductase inhibitor, exhibits anti-metastatic and anti
      tumorigenic effects in endometrial cancer.
AB  - OBJECTIVE: Our goal was to evaluate the effects of simvastatin on endometrial
      cancer cell lines and primary cultures of endometrial cancer cells. METHODS: Cell
      proliferation in the ECC-1 and Ishikawa endometrial cancer cell lines and primary
      cultures of endometrial cancer cells was assessed by MTT assay. Apoptosis and
      cell cycle were detected by Annexin V assay and propidium iodide staining,
      respectively. Reactive oxygen species and cell adhesion were assessed using ELISA
      assays. Invasion was analyzed using a transwell invasion assay. Mitochondrial DNA
      damage was confirmed using qPCR. The effects of simvastatin on the AKT/mTOR and
      MAPK pathways were determined by Western blotting. RESULTS: Simvastatin inhibited
      cell proliferation in a dose-dependent manner in both endometrial cancer cell
      lines and 5/8 primary cultures of endometrial cancer cells. Simvastatin treatment
      resulted in G1 cell cycle arrest, a reduction in the enzymatic activity of HMG
      CoA, induction of apoptosis as well as DNA damage and cellular stress. Treatment
      with simvastatin resulted in inhibition of the MAPK pathway and exhibited
      differential effects on the AKT/mTOR pathway in the ECC-1 and Ishikawa cells.
      Minimal change in AKT phosphorylation was seen in both cell lines. An increase in
      phosphorylated S6 was seen in ECC-1 and a decrease was seen in Ishikawa.
      Treatment with simvastatin reduced cell adhesion and invasion (p<0.01) in both
      cell lines. CONCLUSION: Simvastatin had significant anti-proliferative and anti
      metastatic effects in endometrial cancer cells, possibly through modulation of
      the MAPK and AKT/mTOR pathways, suggesting that statins may be a promising
      treatment strategy for endometrial cancer.

PMID- 24880143
TI  - CD73 expression in RPE cells is associated with the suppression of conventional
      CD4 cell proliferation.
AB  - CD73 is intensively involved in the regulation of immune responses through the
      conversion of pro-inflammatory ATP to immunosuppressive adenosine. Herein, we
      clarified whether cells in the retina express CD73 and participate in the
      regulation of inflammatory eye diseases such as experimental autoimmune uveitis
      (EAU). First, immunofluorescence staining was performed to compare the
      distribution of CD73(+) cells in the retinas of EAU-induced and normal B10RIII
      mice. The results revealed that a layer of cells in the normal retina that was
      consistent with the location of retinal pigment epithelial (RPE) cells strongly
      expressing CD73, and the expression was markedly reduced in the presence of EAU.
      Thereafter, EAU was also induced in C57BL/6 mice by active immunization or
      adoptive transfer. CD73 expression in isolated RPE cells was assessed by real
      time RT-PCR and western blotting, and the catalytic abilities of the cells to
      convert AMP to adenosine were determined using HPLC analyses. Compared to the
      normal control, significantly decreased CD73 expression and AMP catalytic ability
      were found in the RPE cells isolated from inflamed eyes. CD73 expression and
      activity were also studied in cultured RPE cells treated with different stimuli,
      such as Toll-like receptor ligands and cytokines. Highly varied functional CD73
      expression was observed in RPE cells through cytokines or Toll-like receptor
      agonist treatments. Finally, whether RPE cells could regulate the immune
      response, particularly the proliferation of CD4 cells, through surface-expressed
      CD73 was determined using a two-chamber assay. The robust inhibition of
      conventional T-cell proliferation was uniquely observed when CD73(+) RPE cells in
      the upper chamber were in the presence of AMP. To further confirm the function of
      CD73 in RPE cells, Cd73(-/-) RPE cells were isolated, and CD73-rescued control
      cells were constructed. CD73(+)Cd73(-/-) RPE, not Cd73(-/-) RPE, significantly
      suppressed interacted CD4 cells proliferation and cytokine production. Taken
      together, these data suggest that naive RPE cells suppressed the immune response
      through their high expression of CD73. The expression of CD73 in RPE cells could
      be regulated through many factors, and down-regulated CD73 expression attenuated
      the suppressive effect of RPE on the proliferation of conventional CD4 cells. 

PMID- 24880144
TI  - Optical properties of the lens: an explanation for the zones of discontinuity.
AB  - The structural basis of zones of discontinuity in the living human eye lens has
      not been elucidated, and there is no conclusive explanation for what relevance
      they may have to the structure and function of the lens. Newly developed
      synchrotron radiation based X-ray Talbot interferometry has enabled the detection
      of subtle fluctuations in the human eye lens which, when used in mathematical
      modelling to simulate reflected and scattered light, can recreate the image of
      the lens seen in the living human eye. The results of this study show that the
      zones of discontinuity may be caused by subtle fluctuations in the refractive
      index gradient as well as from random scattering in the central regions. As the
      refractive index contours are created by cell layers with progressively varying
      protein concentrations, the zones are linked to growth and will contain
      information about ageing and development. The index gradient is important for
      image quality and fluctuations in this gradient may add to quality optimisation
      and serve as models for designs of new generation implant lenses. 

PMID- 24880145
TI  - Carrier interactions with the biological barriers of the lung: advanced in vitro
      models and challenges for pulmonary drug delivery.
AB  - In recent years significant progress has been made to improve particle deposition
      in the lung. However, the development of strategies to overcome the air-blood
      lung barrier is still needed. The combination of complex in vitro models and
      sophisticated particulate carriers is promising as a strategy by which that goal
      could be achieved. In this review we discuss currently available in vitro lung
      models, including some recent tissue-engineering approaches, as well as the
      challenges associated to implement such complex in vitro systems. Furthermore, we
      discuss available carrier technologies, often based on nanotechnology, to target
      specific regions of the lungs and to overcome the respective biological barriers,
      ideally resulting in safe and effective delivery to the desired pulmonary
      destination. 

PMID- 24880146
TI  - Obesity, metabolic dysfunction, and cardiac fibrosis: pathophysiological
      pathways, molecular mechanisms, and therapeutic opportunities.
AB  - Cardiac fibrosis is strongly associated with obesity and metabolic dysfunction
      and may contribute to the increased incidence of heart failure, atrial
      arrhythmias, and sudden cardiac death in obese subjects. This review discusses
      the evidence linking obesity and myocardial fibrosis in animal models and human
      patients, focusing on the fundamental pathophysiological alterations that may
      trigger fibrogenic signaling, the cellular effectors of fibrosis, and the
      molecular signals that may regulate the fibrotic response. Obesity is associated
      with a wide range of pathophysiological alterations (such as pressure and volume
      overload, metabolic dysregulation, neurohumoral activation, and systemic
      inflammation); their relative role in mediating cardiac fibrosis is poorly
      defined. Activation of fibroblasts likely plays a major role in obesity
      associated fibrosis; however, inflammatory cells, cardiomyocytes, and vascular
      cells may also contribute to fibrogenic signaling. Several molecular processes
      have been implicated in regulation of the fibrotic response in obesity.
      Activation of the renin-angiotensin-aldosterone system, induction of transforming
      growth factor beta, oxidative stress, advanced glycation end-products, endothelin
      1, Rho-kinase signaling, leptin-mediated actions, and upregulation of
      matricellular proteins (such as thrombospondin 1) may play a role in the
      development of fibrosis in models of obesity and metabolic dysfunction. Moreover,
      experimental evidence suggests that obesity and insulin resistance profoundly
      affect the fibrotic and remodeling response after cardiac injury. Understanding
      the pathways implicated in obesity-associated fibrosis may lead to the
      development of novel therapies to prevent heart failure and attenuate
      postinfarction cardiac remodeling in patients with obesity.

PMID- 24880153
TI  - The place of human psychophysics in modern neuroscience.
AB  - Human psychophysics is the quantitative measurement of our own perceptions. In
      essence, it is simply a more sophisticated version of what humans have done since
      time immemorial: noticed and reflected upon what we can see, hear, and feel. In
      the 21st century, when hugely powerful techniques are available that enable us to
      probe the innermost structure and function of nervous systems, is human
      psychophysics still relevant? I argue that it is, and that in combination with
      other techniques, it will continue to be a key part of neuroscience for the
      foreseeable future. I discuss these points in detail using the example of
      binocular stereopsis, where human psychophysics in combination with physiology
      and computational vision, has made a substantial contribution. 

PMID- 24880147
TI  - Epigenetic regulation of fetal globin gene expression in adult erythroid cells.
AB  - The developmental regulation of globin gene expression has served as an important
      model for understanding higher eukaryotic transcriptional control mechanisms.
      During human erythroid development, there is a sequential switch from expression
      of the embryonic epsilon-globin gene to the fetal gamma-globin gene in utero, and
      postpartum the gamma-globin gene is silenced, as the beta-globin gene becomes the
      predominantly expressed locus. Because the expression of normally silenced fetal
      gamma-type globin genes and resultant production of fetal hemoglobin (HbF) in
      adult erythroid cells can ameliorate the pathophysiological consequences of both
      abnormal beta-globin chains in sickle cell anemia and deficient beta-globin chain
      production in beta-thalassemia, understanding the complex mechanisms of this
      developmental switch has direct translational clinical relevance. Of particular
      interest for translational research are the factors that mediate silencing of the
      gamma-globin gene in adult stage erythroid cells. In addition to the regulatory
      roles of transcription factors and their cognate DNA sequence motifs, there has
      been a growing appreciation of the role of epigenetic signals and their cognate
      factors in gene regulation, and in particular in gene silencing through
      chromatin. Much of the information about epigenetic silencing stems from studies
      of globin gene regulation. As discussed here, the term epigenetics refers to
      postsynthetic modifications of DNA and chromosomal histone proteins that affect
      gene expression and can be inherited through somatic cell replication. A full
      understanding of the molecular mechanisms of epigenetic silencing of HbF
      expression should facilitate the development of more effective treatment of beta
      globin chain hemoglobinopathies.

PMID- 24880148
TI  - The nucleosome remodeling and deacetylase complex in development and disease.
AB  - The nucleosome remodeling and deacetylase (NuRD) complex is one of the major
      chromatin remodeling complexes found in cells. It plays an important role in
      regulating gene transcription, genome integrity, and cell cycle progression.
      Through its impact on these basic cellular processes, increasing evidence
      indicates that alterations in the activity of this macromolecular complex can
      lead to developmental defects, oncogenesis, and accelerated aging. Recent genetic
      and biochemical studies have elucidated the mechanisms of NuRD action in
      modifying the chromatin landscape. These advances have the potential to lead to
      new therapeutic approaches to birth defects and cancer. 

PMID- 24880166
TI  - Monocanalicular lacrimonasal intubation.
AB  - A new technique to obtain patency of the lacrimal drainage system was used in
      three children with bilateral congenital obstruction of the lacrimonasal duct
      (six cases) and upper canalicular abnormalities (five cases). The upper
      canalicular abnormalities prevented bicanaliculonasal intubation.A silicone tube
      was passed through the lower canaliculus, traversing the lacrimal drainage system
      and into the nasal fossa. The proximal end of the tube was placed subconjunctival
      in the inferior fornix and secured. The distal end of the tube was passed through
      the subcartilaginous nasal septum to the contralateral nasal fossa and tied to a
      tube similarly passed through the opposite lacrimal system.The procedure was
      successful in all six cases, with all tubes remaining in place the desired length
      of time. Postoperative identification and removal of the tubes offered no
      difficulties and was followed by permanent patency of the lacrimal drainage
      system in all six cases.

PMID- 24880154
TI  - Protection by inosine in a cellular model of Parkinson's disease.
AB  - Inosine (hypoxanthine 9-beta-D-ribofuranoside), a purine nucleoside with multiple
      intracellular roles, also serves as an extracellular modulatory signal. On
      neurons, it can produce anti-inflammatory and trophic effects that confer
      protection against toxic influences in vivo and in vitro. The protective effects
      of inosine treatment might also be mediated by its metabolite urate. Urate in
      fact possesses potent antioxidant properties and has been reported to be
      protective in preclinical Parkinson's disease (PD) studies and to be an inverse
      risk factor for both the development and progression of PD. In this study we
      assessed whether inosine might protect rodent MES 23.5 dopaminergic cell line
      from oxidative stress in a cellular model of PD, and whether its effects could be
      attributed to urate. MES 23.5 cells cultured alone or in presence of enriched
      murine astroglial cultures MES 23.5-astrocytes co-cultures were pretreated with
      inosine (0.1-100 MUM) for 24 h before addition of the oxidative stress inducer
      H2O2 (200 MUM). Twenty-four hours later, cell viability was quantified by 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay or
      immunocytochemistry in pure and MES 23.5-astrocytes co-cultures, respectively.
      H2O2-toxic effect on dopaminergic cells was reduced when they were cultured with
      astrocytes, but not when they were cultured alone. Moreover, in MES 23.5
      astrocytes co-cultures, indicators of free radical generation and oxidative
      damage, evaluated by nitrite (NO2(-)) release and protein carbonyl content,
      respectively, were attenuated. Conditioned medium experiments indicated that the
      protective effect of inosine relies on the release of a protective factor from
      inosine-stimulated astrocytes. Purine levels were measured in the cellular
      extract and conditioned medium using high-performance liquid chromatography
      (HPLC) method. Urate concentration was not significantly increased by inosine
      treatment however there was a significant increase in levels of other purine
      metabolites, such as adenosine, hypoxanthine and xanthine. In particular, in MES
      23.5-astrocytes co-cultures, inosine medium content was reduced by 99% and
      hypoxanthine increased by 127-fold. Taken together these data raise the
      possibility that inosine might have a protective effect in PD that is independent
      of any effects mediated through its metabolite urate.

PMID- 24880156
TI  - Ammonia concentration at emergence and its effects on the recovery of different
      species of entomopathogenic nematodes.
AB  - The life cycle of entomopathogenic nematodes (EPN) occurs inside an insect
      cadaver and an accumulation of ammonia initiates as a consequence of the
      nematodes defecation. This accumulation reduces the food resources quality and
      creates a detrimental environment for nematodes. When a given ammonia
      concentration is reached, the nematodes start their emergence process, searching
      for a new host. In the present work, this parameter, ammonia triggering point
      (ATP) was measured in 7 Steinernema species/strains. The effect of different
      ammonia concentrations on the recovery process and their consequences in the
      nematodes survival were also investigated. The results indicate that ATP varies
      among nematode species; Steinernema glaseri showed the highest ATP of the
      evaluated species (1.98+/-2.6 mg of NH4-N*g of Galleria mellonella(-1)); whereas
      Steinernema riobrave presented the lowest ATP (1.16+/-0.1 mg of NH4-N*g of G.
      mellonella(-1)). On the other hand, the nematode emergence could be a repulsive
      response when ATP is reached. As the ammonia concentration increased the recovery
      percentage of Steinernema feltiae (Chile strain) dropped gradually from 79.4+/
      11.9% in the control treatment to 0% when 1mg of NH4-N*ml of bacterial broth(-1)
      was added. It is possible, that emergence process could be a repulsive response
      of the nematodes due to ammonia concentration when is reaching the ATP. The role
      of ammonia inside the insect cadavers, might suggests connections with some
      stages of the EPN life cycle.

PMID- 24880174
TI  - Optokinetic asynunetry in esotropia.
AB  - Laboratory evidence suggests that the interruption of binocularity produced by
      early onset strabismus inhibits normal development of cortical inputs to the
      brainstem optokinetic pathway, producing an asymmetry in monocular optokinetic
      responses. It has been proposed that this optokinetic asymmetry can be useful in
      evaluating the presence of binocular vision. We studied 134 strabismic and 16
      orthotopic patients to determine the clinical prevalence of asymmetric
      optokinetic responses. Cooperative children and adults were tested. For each
      subject, the observer made a judgment about the presence or absence of symmetry
      in the nasally directed versus temporally directed monocular optokinetic
      responses to motion of a hand-held drum.Clinical evidence of significantly
      greater nasally than temporally directed optokinetic responses was observed in
      58% of esotropie patients who developed strabismus before the age of 6 months; in
      22% of esotropie patients with onset between 6 and 12 months of age; in 9% of
      esotropie patients with onset between 12 and 24 months of age; and in only 5% of
      esotropie patients with onset of esotropia after the age of 24 months. No
      asymmetry was observed in any of the exotropic patients or in the hypertropic
      patient and was present in only 6% of orthotropic patients. Statistical analysis
      indicates that in this population the finding of monocular optokinetic asymmetry
      in an esotropie patient implies an 85% chance that the onset of esotropia
      occurred in the first 6 months of life. Quantitative electro-oculographic
      recording demonstrated that the clinical evaluation of optokinetic asymmetry can
      detect high degrees of asymmetry, but may miss subtle ones. Dissociated vertical
      deviation and latent nystagmus were not consistently associated with asymmetry of
      the monocular optokinetic responses.It may be concluded that clinically evident
      asymmetry of monocular optokinetic response is strong evidence for esotropia of
      early onset, while the absence of such asymmetry does not rule out early onset.
      Other manifestations of infantile esotropia, such as latent nystagmus and
      dissociated vertical deviation, are not invariably associated with optokinetic
      asymmetry.

PMID- 24880184
TI  - Long-term follow-up of Jensen procedures.
AB  - Jensen procedures were performed on 29 eyes of 26 patients with lateral rectus
      palsy between January 1972 and July 1985. The cases were reviewed retrospectively
      to assess efficacy of the procedure and long-term stability. The patients were
      evaluated preoperatively with prism cover test, versions, forced auctions,
      saccadic velocities, and diplopia fields. All patients were observed
      preoperatively for at least 6 months and had no further recovery of function.
      Eighteen eyes had less than 20% of normal abduction saccadic velocity; nine eyes
      had 20% to 40%; two could not be assessed with saccadic velocities. The procedure
      was a Jensen's union combined with a medial rectus recession on adjustable
      suture. The average follow-up was 4 years. Twenty-four patients had good head
      positions and fusion with a functional area of single binocular vision, averaging
      41 horizontally. All patients demonstrated improved saccadic velocities, with
      similar improvement for those beginning with less than 20% abduction saccadic
      velocity and those with 20%-40%. A single case of anterior segment ischemia is
      reported.

PMID- 24880180
TI  - Recurrent esotropia.
AB  - Recurrent esotropia is characterized by repeated recurrence of the preoperative
      angle of strabismus after initial operative alignment. It occurred in 19 of
      approximately 3,000 patients operated on for esotropia with an onset of birth or
      in childhood during a 10-year period. Among the etiologic factors to be
      considered are progressive and under corrected hypermetropia, the nystagmus
      blockage syndrome, the blind spot syndrome, abnormal fusional movements, an
      unstable high AC/A ratio, and non-accommodative convergence excess. None of these
      factors played an exclusive role in our patients.

PMID- 24880185
TI  - Lupus erythematosus induced by terbinafine in a patient with systemic lupus
      erythematosus.

PMID- 24880186
TI  - Refusal to medical interventions.
AB  - Refusal to medical interventions is the not acceptance, voluntary and free, of an
      indicated medical intervention. What the physician should do in case of refusal?
      It is understandable that the rejection of a validated medical intervention is
      difficult to accept by the responsible physician when raises the conflict
      protection of life versus freedom of choice. Therefore it is important to follow
      some steps to incorporate the most relevant aspects of the conflict. These steps
      include: 1) Give complete information to patients, informing on possible
      alternatives, 2) determine whether the patient can decide (age, competency and
      level of capacity), 3) to ascertain whether the decision is free, 4) analyze the
      decision with the patient, 5) to persuade, 6) if the patient kept in the
      rejection decision, consider conscientious objection, 7) take the decision based
      on the named criteria, 8) finally, if the rejection is accepted, offer available
      alternatives. 

PMID- 24880187
TI  - [American Academy of Neurology, Philadelphia, 26 April-3 May, 2014].

PMID- 24880188
TI  - Acceptability of self-collected versus provider-collected sampling for HPV DNA
      testing among women in rural El Salvador.
AB  - OBJECTIVE: To determine the acceptability of self-collected versus provider
      collected sampling among women participating in public sector HPV-based cervical
      cancer screening in El Salvador. METHODS: Two thousand women aged 30-49 years
      underwent self-collected and provider-collected sampling with careHPV between
      October 2012 and March 2013 (Qiagen, Gaithersburg, MD, USA). After sample
      collection, a random sample of women (n=518) were asked about their experience.
      Participants were questioned regarding sampling method preference, previous
      cervical cancer screening, HPV and cervical cancer knowledge, HPV risk factors,
      and demographic information. RESULTS: All 518 women approached to participate in
      this questionnaire study agreed and were enrolled, 27.8% (142 of 511 responding)
      of whom had not received cervical cancer screening within the past 3 years and
      were considered under-screened. Overall, 38.8% (n=201) preferred self-collection
      and 31.9% (n=165) preferred provider collection. Self-collection preference was
      associated with prior tubal ligation, HPV knowledge, future self-sampling
      preference, and future home-screening preference (P<0.05). Reasons for self
      collection preference included privacy/embarrassment, ease, and less pain;
      reasons cited for provider-collection preference were result accuracy and
      provider knowledge/experience. CONCLUSION: Self-sampling was found to be
      acceptable, therefore screening programs could consider offering this option
      either in the clinic or at home. Self-sampling at home may increase coverage in
      low-resource countries and reduce the burden that screening places upon clinical
      infrastructure.

PMID- 24880189
TI  - The loss of a mother and dealing with genetic cancer risk: women who have
      undergone prophylactic removal of the ovaries.
AB  - PURPOSE: The purpose of this article is to highlight some new findings from a
      qualitative study that have not been previously considered. METHOD: The research
      was based on a qualitative phenomenological method. Data were collected by semi
      structured individual interviews. A purposeful sample was recruited from West
      Norway of 14 women with a possible risk of developing breast and ovarian cancer.
      Data collection took place at least one year after prophylactic removal of the
      ovaries. Data from the study was analyzed according to the phenomenological
      method of Amedeo Giorgi. KEY FINDINGS: Two themes were revealed as essential
      factors of the interviewed women's experiences: "the loss of a mother" and
      "dealing with genetic cancer risk." For the most part, these two themes also
      appeared to be interrelated. When a mother died of ovarian cancer while her
      daughter was a child or a young woman, this often led to her daughter's strong
      desire to find an explanation for her mother's death, as well as to her efforts
      to undergo genetic testing and surgery to prevent cancer in her family in the
      future. CONCLUSION: The study indicates that women's experiences in families at
      risk of hereditary cancer are closely related to an understanding of their life
      stories, particularly their "loss of a mother," and how this influences how they
      deal with genetic cancer risk. Health care workers can thus help patients
      identify connections and establish coherence through the act of storytelling, by
      listening to their illness experiences as part of their life stories.

PMID- 24880190
TI  - Cardiovascular risk in rheumatoid arthritis.
AB  - The objectives of this review are to discuss data on the cardiovascular risk
      increase associated with rheumatoid arthritis (RA), the effects of RA treatments
      on the cardiovascular risk level, and the management of cardiovascular risk
      factors in patients with RA. Overall, the risk of cardiovascular disease is
      increased 2-fold in RA patients compared to the general population, due to the
      combined effects of RA and conventional risk factors. There is some evidence that
      the cardiovascular risk increase associated with nonsteroidal anti-inflammatory
      drug therapy may be smaller in RA patients than in the general population.
      Glucocorticoid therapy increases the cardiovascular risk in proportion to both
      the current dose and the cumulative dose. Methotrexate and TNFalpha antagonists
      diminish cardiovascular morbidity and mortality rates. The management of
      dyslipidemia remains suboptimal. Risk equations may perform poorly in RA patients
      even when corrected using the multiplication factors suggested by the EUropean
      League Against Rheumatism (EULAR) (multiply the score by 1.5 when two of the
      following three criteria are met: disease duration longer than 10 years, presence
      of rheumatoid factor or anti-cyclic citrullinated peptide (CCP) antibodies, and
      extraarticular manifestations). Doppler ultrasonography of the carotid arteries
      in patients at moderate cardiovascular risk may allow a more aggressive approach
      to dyslipidemia management via reclassification into the high-risk category of
      patients with an intima-media thickness greater than 0.9 mm or atheroma plaque.

PMID- 24880192
TI  - An ignored lighthouse: is there underappreciation and underutilization of electro
      magnetic source imaging?

PMID- 24880191
TI  - An atypical sciatica revealing a rhabdomyolysis.

PMID- 24880193
TI  - The effect of insertion angle on the pullout strength of threaded suture anchors:
      a validation of the deadman theory.
AB  - PURPOSE: To determine the effect of insertion angle, from 45 degrees  to 135
      degrees  in 15 degrees  increments, on the number of cycles withstood, the
      ultimate pullout strength, and the stiffness of threaded suture anchors subjected
      to load. METHODS: Threaded anchors were inserted into polyurethane foam at angles
      from 45 degrees  to 135 degrees , in 15 degrees  increments, relative to the
      direction of pull. Five anchors were tested at each angle. The anchors were first
      cycled for 30 cycles (10 each at 100 N, 150 N, and 200 N). The surviving
      specimens were then tensioned to failure. The McNemar test was used to compare
      cyclic failure rates. Paired-samples t tests were used to compare load-to-failure
      (LTF) and stiffness data. All P values are multiplicity adjusted by the Hommel
      procedure. RESULTS: Four of 5 anchors inserted at 45 degrees  failed during
      cyclic testing at a mean of 27 cycles (P = .13). One of 5 anchors placed at 60
      degrees  failed after 29 cycles (P = .99). All other anchors survived cyclic
      testing. Mean LTF was 234 N, 243 N, 297 N, 373 N, 409 N, 439 N, and 417 N at
      insertion angles of 45 degrees , 60 degrees , 75 degrees , 90 degrees , 105
      degrees , 120 degrees , and 135 degrees , respectively. LTF was significantly
      less for the 60 degrees  group when compared with the 90 degrees , 105 degrees ,
      120 degrees , and 135 degrees  groups (P < .05). LTF was significantly less for
      the 75 degrees  group when compared with the 105 degrees , 120 degrees , and 135
      degrees  groups (P < .05). For the 90 degrees  group, LTF was only significantly
      less when compared with the 135 degrees  group (P = .022). The differences in LTF
      between the 105 degrees , 120 degrees , and 135 degrees  groups were not
      significant. Stiffness increased from 28.13 N/mm at 90 degrees  to 43.4 N/mm at
      105 degrees  (P = .03), 61.48 N/mm at 120 degrees  (P = .003), and 86.83 N/mm at
      135 degrees  (P = .008). CONCLUSIONS: Anchors placed at more acute angles, that
      is, anchors placed closer to the so-called deadman's angle, failed at lower loads
      and provided less construct stiffness than anchors placed at angles greater than
      90 degrees . Stiffness also increased sequentially from an angle of insertion of
      90 degrees  up to our maximum angle tested of 135 degrees . For threaded metallic
      suture anchors, an obtuse insertion angle of 90 degrees  to 135 degrees  in
      relation to the line of pull of the suture and rotator cuff withstands a greater
      LTF and provides a stiffer construct than the more acute insertion angle
      advocated by the "deadman theory." CLINICAL RELEVANCE: This study offers a
      biomechanical validation for optimal placement of threaded suture anchors at an
      angle of 90 degrees  or more, as anatomic restraints allow, from the vector of
      pull of the attached suture and rotator cuff, rather than the 45 degrees  angle
      recommended by the deadman theory.

PMID- 24880194
TI  - Effect of ultrasonographically guided axillary nerve block combined with
      suprascapular nerve block in arthroscopic rotator cuff repair: a randomized
      controlled trial.
AB  - PURPOSE: The aim of this study was to compare the results of ultrasonographically
      guided axillary nerve block (ANB) combined with suprascapular nerve block (SSNB)
      with those of SSNB alone on postoperative pain and satisfaction within the first
      48 hours after arthroscopic rotator cuff repair. METHODS: Forty-two patients with
      rotator cuff tears who had undergone arthroscopic rotator cuff repair were
      enrolled in this study. Among them, 21 patients were randomly allocated to group
      1 and received both SSNB and ANB with 10 mL ropivacaine. The other 21 patients
      were allocated to group 2 and received SSNB with 10 mL 0.75% ropivacaine and ANB
      with 10 mL saline. Visual analog scale (VAS) pain score, patient satisfaction
      (SAT), and lateral pain index (LPI) was checked at 1, 3, 6, 12, 18, 24, 36, and
      48 hours postoperatively. RESULTS: Group 1 showed a significantly lower mean VAS
      score at postoperative 1, 3, 6, 12, 18, and 24 hours compared with group 2 (5.1 <
      7.6, 4.4 < 6.3, 3.7 < 5.3, 3.2 < 4.5, 2.7 < 4.0, and 2.7 < 3.4, respectively). A
      significantly high mean SAT and low mean LPI was observed in group 1 at
      postoperative 1, 3, 6, 12, 18, 24, and 36 hours (4.9 > 2.4, 5.9 > 3.7, 6.3 > 5.0,
      6.8 > 5.7, 7.3 > 6.2, 7.5 > 6.6, and 7.7 > 7.0, respectively), (1.1 < 3.0, 0.8 <
      2.5, 0.7 < 2.0, 0.7 < 1.6, 0.6 < 1.3, 0.6 < 1.0, and 0.4 < 0.7, respectively).
      The frequency of rebound pain decreased in group 1 compared with group 2 (P =
      .032). In addition, rebound phenomenon showed a correlation with ANB on
      univariate logistic regression (P = .034; odds ratio, 0.246). CONCLUSIONS:
      Ultrasonographically guided ANB combined with SSNB in arthroscopic rotator cuff
      repair showed an improved mean VAS in the first 24 hours after surgery compared
      with SSNB alone. The mean SAT and LPI of the combined blocks were better than
      those of the single block within the first 36 hours. Ultrasonographically guided
      ANB combined with SSNB also decreased the rebound phenomenon. LEVEL OF EVIDENCE:
      Level I, randomized controlled trial.

PMID- 24880196
TI  - High prevalence of aspirin resistance in elderly patients with cardiovascular
      disease (CVD) and hyperhomocysteinaemia.
AB  - Although aspirin resistance is well reported in CVD, little is known about
      aspirin response in elderly patients with hyperhomocysteinaemia. The aim of the
      present study was to explore the prevalence of aspirin resistance in elderly
      patients with CVD and hyperhomocysteinaemia. A total of 370 elderly patients with
      CVD were recruited. The study included 216 patients with hyperhomocysteinaemia
      and 154 patients with normohomocysteinaemia receiving daily aspirin therapy (>=
      75 mg) over 1 month. The effect of aspirin was assessed using by light
      transmission aggregometry (LTA). Aspirin resistance was defined as >= 20%
      arachidonic acid induced aggregation according to LTA. Aspirin resistance was
      defined in 48 (13.0%) of 370 patients. The prevalence of aspirin resistance was
      higher in hyperhomocysteinaemic patients than normohomocysteinaemic patients
      (16.7% vs. 7.8%, odds ratio (OR)=2.367; 95% confidence interval (CI)=1.188-4.715,
      p=0.012). In the multivariate logistic regression analysis, hyperhomocysteinaemia
      (OR=2.406, 95% CI=1.201-4.820, p=0.013) was a significant risk factor for aspirin
      resistance. A significant number of CVD patients with hyperhomocysteinemia are
      resistant to aspirin therapy. Hyperhomocysteinemia is a significant risk factor
      for aspirin resistance in elderly patients with CVD.

PMID- 24880197
TI  - Anserine and carnosine supplementation in the elderly: Effects on cognitive
      functioning and physical capacity.
AB  - The aim of this study was to investigate the potential beneficial effects of
      dietary anserine and carnosine (CRC) supplementation on cognitive functioning and
      physical activity of the elderly. The fifty-six subjects (65+) were allocated to
      the CRC group or placebo group at a 1:1 ratio. The double-blind procedure was
      used. Data were collected at the baseline and after 13-weeks of supplementation.
      In the follow up procedure fifty one subjects took part. Chicken meat extract
      (CME) containing 40% of CRC components (2:1 ratio of anserine to carnosine) was
      administered 2.5 g per day which allowed to rich the level of 1g CRC in
      dipeptides supplement. The cognitive function, physical capacity, body
      measurements, blood pressure and heart rate (HR) were assessed. After
      supplementation Body Mass Index (BMI) decreased significantly (p<0.05) in the CRC
      group performance comparing the placebo group. In two of six Senior Fitness Test
      the scores increased significantly (p<0.05) in CRC group comparing to the placebo
      group. The perceived exertion differed significantly (p<0.05) at the baseline and
      after follow up at the CRC group. The mean values of the Short Test of Mental
      Status (STMS) scores showed the significant (p<0.04) increase only in CRC group,
      in the subscores of construction/copying, abstraction and recall. Conducted
      anserine and carnosine supplementation in the elderly brings promising effects on
      cognitive functioning and physical capacity of participants. However, further
      studies are needed.

PMID- 24880195
TI  - Benzodiazepine (BZD) use in community-dwelling older adults: Longitudinal
      associations with mobility, functioning, and pain.
AB  - The aim of the study was to determine the prospective association between
      baseline BZD use and mobility, functioning, and pain among urban and rural
      African-American and non-Hispanic white community-dwelling older adults. From
      1999 to 2001, a cohort of 1000 community-dwelling adults, aged >= 65 years,
      representing a random sample of Medicare beneficiaries, stratified by ethnicity,
      sex, and urban/rural residence were recruited. BZD use was assessed at an in-home
      visit. Every six months thereafter, study outcomes were assessed via telephone
      for 8.5-years. Mobility was assessed with the Life-Space Assessment (LSA).
      Functioning was quantified with level of difficulty in five basic activities of
      daily living (ADL: bathing, dressing, transferring, toileting, eating), and six
      instrumental activities of daily living (IADL: shopping, managing money,
      preparing meals, light and heavy housework, telephone use). Pain was measured by
      frequency per week and the magnitude of interference with daily tasks. All
      analytic models were adjusted for relevant covariates and mental health symptoms.
      After multivariable adjustment, baseline BZD use was significantly associated
      with greater difficulty with basic ADL (Estimate=0.39, 95% confidence interval
      (CI): 0.04-0.74), and more frequent pain (Estimate=0.41, 95%CI: 0.09-0.74) in the
      total sample and declines in mobility among rural residents (Estimate=-0.67,
      t(5,902)=-1.98, p=0.048), over 8.5 years. BZD use was prospectively associated
      with greater risk for basic ADL difficulties and frequent pain among African
      American and non-Hispanic white community-dwelling older adults, and life-space
      mobility declines among rural-dwellers, independently of relevant covariates.
      These findings highlight the potential long-term negative impact of BZD use among
      community-dwelling older adults.

PMID- 24880198
TI  - [Definition and biomarkers of acute renal damage: new perspectives].
AB  - The RIFLE and AKIN criteria have definitely help out to draw attention to the
      relationship between a deterioration of renal function that produces a small
      increase in serum creatinine and a worse outcome. However, the specific clinical
      utility of using these criteria remains to be well-defined. It is believed that
      the main use of these criteria is for the design of epidemiological studies and
      clinical trials to define inclusion criteria and objectives of an intervention.
      AKI adopting term, re-summoning former ARF terminology, it is appropriate to
      describe the clinical condition characterized by damage to kidney, in the same
      way as the term is used to describe acute lung damage where the lung injury
      situation still has not increased to a situation of organ failure (dysfunction).
      The serum and urine biomarkers (creatinine, urea, and diuresis) currently in use
      are not sensitive or specific for detecting kidney damage, limiting treatment
      options and potentially compromising the outcome. New biomarkers are being
      studied in order to diagnose an earlier and more specific AKI, with the potential
      to change the definition criteria of AKI with different stages, currently based
      in diuresis and serum creatinine.

PMID- 24880199
TI  - Knee adduction moment and medial knee contact force during gait in older people.
AB  - External knee adduction moment has been studied as a surrogate for medial knee
      contact force. However, it is not known whether adduction moment is a rational
      measure for predicting medial knee contact force. The aim of this study was to
      investigate the correlation between knee adduction moment and medial knee contact
      force in older people, using musculo-skeletal simulation analysis. One hundred
      and twenty-two healthy older subjects participated in this study. Knee moment and
      medial knee contact force were calculated based on inverse dynamics analysis of
      normal walking. Muscle force and joint reaction force were used to determine the
      medial knee contact force during stance phase. The results showed that the
      maximum medial knee contact force was moderately correlated to the maximum knee
      adduction (r = 0.59) as well as the maximum extension moment (r = 0.60). The
      first peak of medial knee contact force had a significant strong correlation with
      the first peak of adduction moment and a moderate correlation with the maximum
      flexion moment. The second peak of medial knee contact force had a significant
      moderate correlation with both the second peak of adduction and the maximum
      extension moment. These results implied that the maximum adduction moment value
      could be used, to some extent, as a measure of the maximum medial knee contact
      force.

PMID- 24880200
TI  - A comparative assessment and gap analysis of commonly used team rating scales.
AB  - BACKGROUND: The purpose of this article was to conduct a gap analysis of
      important team constructs that may be absent in widely used team assessments.
      METHODS AND MATERIALS: Two assessment tools with known validity evidence (1) Non
      Technical Skills for Surgeons (NOTSS) and (2) the Cannon-Bowers Scale were used
      to evaluate 11 teams of surgical residents (n = 33) performing simulated
      laparoscopic hernia repairs. Faculty raters' scores were used to compare the
      surveys and assess validity and reliability. Raters' detailed observation notes
      were used to indicate important behavioral constructs that were missing from the
      team rating scales. RESULTS: When assessing inter-item correlations (reliability)
      four of five NOTSS' scale items had significant correlations (r = 0.9-1.0, P <
      0.05) with the Cannon-Bowers items. While the correlations were only noted for
      three of six Cannon-Bowers items, in each instance the same four of five NOTSS
      items correlated with the three Cannon-Bowers items, thus providing further
      validity evidence for both scales. When evaluating the gap, key emerging themes
      included the need to focus on critical team errors, individual team member
      contributions, task performance, and overall team performance. These gaps, plus
      items from the NOTSS and Cannon-Bowers scales, were incorporated into a new
      rating scale. CONCLUSIONS: Despite continued evidence of validity and
      reliability, there were several behavioral constructs that were not represented
      when using the NOTSS and Cannon-Bowers scales. Critical team errors, individual
      team member contributions, task performance, and overall team performance appear
      important in our ability to understand teams and teamwork.

PMID- 24880202
TI  - Utility of routine postoperative visit after appendectomy and cholecystectomy
      with evaluation of mobile technology access in an urban safety net population.
AB  - BACKGROUND: The value of routine postoperative visits after general surgery
      remains unclear. The objective of this study was to evaluate the utility of
      routine postoperative visits after appendectomy and cholecystectomy and to
      determine access to mobile technology as an alternative platform for follow-up.
      METHODS: Retrospective review of 219 appendectomies and 200 cholecystectomies
      performed at a safety net hospital. One patient underwent both surgeries. Patient
      demographics, duration of clinic visit, and need for additional imaging, tests or
      readmissions were recorded. Access to mobile technology was surveyed by a
      validated questionnaire. RESULTS: Of 418 patients, 84% percent completed a
      postoperative visit. At follow-up, 58 patients (14%) required 70 interventions,
      including staple removal (16, 23%), suture removal (4, 6%), drain removal (8,
      11%), additional follow-up (20, 28%), medication action (16, 21%), additional
      imaging (3, 4%), and readmission (1, 1%). Occupational paperwork (62) and
      nonsurgical clinic referrals (28) were also performed. Average check-in to check
      out time was 100 +/- 54 min per patient. One intervention was performed for every
      7.8 h of time in the clinic. Additionally, 88% of the surveyed population
      reported access to cell phone technology, and 69% of patients <40 y had
      smartphone access. CONCLUSIONS: Routine in-person follow-up after surgery
      consumes significant time and resources for patients and healthcare systems but
      has little impact on patient care. Most of the work done in the clinic is
      administrative and could be completed using mobile technology, which is pervasive
      in our population.

PMID- 24880203
TI  - [Facing the new phase of Anales de Pediatria].

PMID- 24880201
TI  - Carbonic anhydrase 4 and crystallin alpha-B immunoreactivity may distinguish
      benign from malignant thyroid nodules in patients with indeterminate thyroid
      cytology.
AB  - BACKGROUND: Thyroid nodules are present in 19%-67% of the population and carry a
      5%-10% risk of malignancy. Unfortunately, fine-needle aspiration biopsies are
      indeterminate in 20%-30% of patients, often necessitating thyroid surgery for
      diagnosis. Numerous DNA microarray studies including a recently commercialized
      molecular classifier have helped to better distinguish benign from malignant
      thyroid nodules. Unfortunately, these assays often require probes for >100 genes,
      are expensive, and only available at a few laboratories. We sought to validate
      these DNA microarray assays at the protein level and determine whether simple and
      widely available immunohistochemical biomarkers alone could distinguish benign
      from malignant thyroid nodules. METHODS: A tissue microarray (TMA) composed of 26
      follicular thyroid carcinomas (FTCs) and 53 follicular adenomas (FAs) from
      patients with indeterminate thyroid nodules was stained with 17
      immunohistochemical biomarkers selected based on prior DNA microarray studies.
      Antibodies used included galectin 3, growth and differentiation factor 15,
      protein convertase 2, cluster of differentiation 44 (CD44), glutamic oxaloacetic
      transaminase 1 (GOT1), trefoil factor 3 (TFF3), Friedreich Ataxia gene (X123),
      fibroblast growth factor 13 (FGF13), carbonic anhydrase 4 (CA4), crystallin alpha
      B (CRYAB), peptidylprolyl isomerase F (PPIF), asparagine synthase (ASNS), sodium
      channel, non-voltage gated, 1 alpha subunit (SCNN1A), frizzled homolog 1 (FZD1),
      tyrosine related protein 1 (TYRP1), E cadherin, type 1 (ECAD), and thyroid
      hormone receptor associated protein 220 (TRAP220). Of note, two of these
      biomarkers (GOT1 and CD44) are now used in the Afirma classifier assay. We chose
      to compare specifically FTC versus FA rather than include all histologic
      categories to create a more uniform immunohistochemical comparison. In addition,
      we have found that most papillary thyroid carcinoma could often be reasonably
      distinguished from benign disease by morphological cytology findings alone.
      RESULTS: Increased immunoreactivity of CRYAB was associated with thyroid
      malignancy (c-statistic, 0.644; negative predictive value [NPV], 0.90) and loss
      of immunoreactivity of CA4 was also associated with malignancy (c-statistic,
      0.715; NPV, 0.90) in indeterminate thyroid specimens. The combination of CA4 and
      CRYAB for discriminating FTC from FA resulted in a better c-statistic of 0.75,
      sensitivity of 0.76, specificity of 0.59, positive predictive value (PPV) of
      0.32, and NPV of 0.91. When comparing widely angioinvasive FTC from FA, the
      resultant c-statistic improved to 0.84, sensitivity of 0.75, specificity of 0.76,
      PPV of 0.11, and NPV of 0.99. CONCLUSIONS: Loss of CA4 and increase in CRYAB
      immunoreactivity distinguish FTC from FA in indeterminate thyroid nodules on a
      thyroid TMA with an NPV of 91%. Further studies in preoperative patient fine
      needle aspiration (FNAs) are needed to validate these results.

PMID- 24880204
TI  - [Towards a Spanish Paediatric Association of excellence].

PMID- 24880205
TI  - Epidemiology of Monoclonal Gammopathy of Undetermined Significance (MGUS): The
      experience from the specialized registry of hematologic malignancies of Basse
      Normandie (France).
AB  - Multiple myeloma (MM) is the third most common haematologic malignancy in
      European countries, and is usually preceded by Monoclonal Gammopathy of
      Undetermined Significance (MGUS). Therefore epidemiologic studies of MGUS are
      very limited in a population-based status. Here we report all new cases of MGUS
      exhaustively recorded by the Basse-Normandie Regional Registry for Hematologic
      Malignancies (a French region registry) between January 1997 and December 2005,
      and analyze outcome of patients until 2009 in term of evolution in MM or death.
      All cases were analyzed by an expert file review, and MGUS diagnosis was retained
      for: evidence of a monoclonal component <30 g/l and no CRAB criteria
      (hyperCalcemia, renal insufficiency, anemia, bone lesions). We showed that the
      world standardized incidence rate (WSR) for MGUS was 3.76 +/- 0.26 per 100,000
      inhabitants, increasing regularly with age, and that the median overall survival
      (OS) was 115.9 months (CI 95%: 10.5-130.2 months) with 78.3% patients alive at 5
      years (CI 95%: 74.1-81.9%). We also observed a rate of progression to multiple
      myeloma of 1.41% per year, concordant with previous reports in a reallife
      exhaustive registry.

PMID- 24880206
TI  - Gout: joints and beyond, epidemiology, clinical features, treatment and co
      morbidities.
AB  - Gout is a common inflammatory arthritis precipitated by an inflammatory reaction
      to urate crystals in the joint. Gout is increasingly being recognised as a
      disease primarily of urate overload with arthritis being a consequence of this
      pathological accumulation. It is associated with a number of important co
      morbidities including chronic kidney disease, obesity, diabetes and
      cardiovascular disease. The prevalence of gout is increasing around the world.
      Significant progress has been made in determining the genetic basis for both gout
      and hyperuricaemia. Environmental risk factors for gout have been identified as
      certain foods, alcohol and several medications. There is, however, little
      evidence that changing these environmental risks improves gout on an individual
      level. Treatment of gout encompasses two strategies: firstly treatment of
      inflammatory arthritis with non-steroidal anti-inflammatories, corticosteroids,
      colchicine or interleukin-1 inhibitors. The second and most important strategy is
      urate lowering, to a target of 0.36 mmol/L (6 mg/dL) or potentially lower in
      those with tophi (collections of crystalline urate subcutaneously). Along with
      urate lowering, adequate and prolonged gout flare prophylaxis is required to
      prevent the precipitation of acute attacks. Newer urate lowering agents are in
      development and have the potential to significantly expand the potential
      treatment options. Education of patients regarding the importance of life long
      urate lowering therapy and prophylaxis of acute attacks is critical to treatment
      success as adherence with medication is low in chronic diseases in general but
      especially in gout.

PMID- 24880207
TI  - Muscle thickness measurements to estimate gluteus medius and minimus activity
      levels.
AB  - The clinical assessment of gluteus medius and minimus force sharing requires non
      invasive measurements of individual activity levels. Do ultrasound measurements
      of change of muscle thickness substitute invasive electromyography (EMG)?
      Isometric hip abduction in 20-80% maximal voluntary isometric contraction (MVIC)
      was measured using dynamometry, M-mode ultrasound for gluteus medius and minimus
      thickness and EMG using (1) surface electrodes on gluteus medius, n = 15, (2)
      fine-wire electrodes in deep gluteus medius and minimus, n = 6. Gluteus medius
      thickened by 5.0 (SD 2.5) mm at 80% MVIC while gluteus minimus thickness was
      constant in the surface EMG study and decreased by 1.6 (SD 1.6) mm at the more
      ventral location in the fine-wire EMG study. Thickness change of gluteus medius
      enabled prediction of torque (r(2) 0.66) and of surface EMG amplitude (r(2)
      0.57). Surface EMG enabled higher torque prediction (r(2) 0.84) than thickness
      change. Thickness change of gluteus minimus did not enable a practically relevant
      estimation of torque production. Ultrasound examination revealed a differential
      thickening behaviour of gluteus medius and minimus which enabled estimation of
      isometric torque production only for gluteus medius but with lower precision than
      surface EMG. 

PMID- 24880208
TI  - Papillary muscle rupture associated to essential thrombocytosis.
AB  - Essential thrombocytosis (ET) falls under the umbrella of myeloproliferative
      disorders, which also includes chronic myelogenous leukemia, polycythemia vera,
      and myelofibrosis with myeloid metaplasia. Essential thrombocytosis results from
      a clonal proliferation of megakaryocites within the bone marrow, leading to an
      absolute elevation of platelets that can cause both hemorrhagic and thrombotic
      complications.

PMID- 24880210
TI  - Dating violence and interpersonal victimization among a national sample of Latino
      youth.
AB  - PURPOSE: The purpose of this analysis was (1) to provide the rates of dating
      violence victimization among a national sample of Latino adolescents, (2) to
      determine the degree to which different forms of dating violence victimization co
      occurred for this sample, and (3) to determine how much dating violence
      victimization overlapped with other forms of non-partner-perpetrated
      victimization. METHOD: This analysis used data from the Dating Violence Among
      Latinos Study, which surveyed 1,525 Latino adolescents between the ages of 12 and
      18 years about past-year dating violence and non-partner-perpetrated
      victimization. We calculated victimization rates and relative risk ratios to
      evaluate the co-occurrence among different forms of dating violence victimization
      as well as the co-occurrence of dating violence and other forms of victimization.
      RESULTS: Results show elevated rates of dating violence victimization compared
      with previous studies, which is primarily accounted for by psychological dating
      violence. The rate of dating violence appears to precipitously increase starting
      around ages 13 and 14 years and is consistently higher for boys. Each type of
      dating violence was significantly associated with other forms of dating violence
      (e.g., physical and psychological). Dating violence was significantly associated
      with experiencing conventional crime, peer or sibling victimization, and
      nonpartner sexual victimization as well as being a polyvictim. CONCLUSIONS: The
      results support the importance of early prevention efforts with Latino youth and
      addressing dating violence with both sexes. Furthermore, dating violence should
      be seen as a potential risk marker for youth who are experiencing multiple forms
      of victimization.

PMID- 24880209
TI  - Soluble fms-like tyrosine kinase-1 in HIV infected pre-eclamptic South African
      Black women.
AB  - INTRODUCTION: Hypertensive disorders of pregnancy are the commonest direct cause
      of maternal deaths in South Africa, 83% being attributed to pre-eclampsia.
      Elevated placental sFlt-1 levels are linked with angiogenic disruption and
      subsequent pre-eclampsia development. The impact of HIV infection on pre
      eclampsia is controversial. Its effect on angiogenic imbalance in both
      normotensive and pre-eclamptic pregnancies remains unknown. METHODS: We examined
      the immunolocalisation of both membrane bound and soluble forms of Flt-1, within
      placentae of HIV negative and positive normotensive and pre-eclamptic pregnancies
      at term using immunohistochemistry and immuno-electron microscopy. RESULTS:
      Strong Flt-1 and sFlt-1 immunoreactivity was observed within endothelial,
      syncytio and cytotrophoblast cells. Subcellularly, gold particles were localised
      predominantly within the endoplasmic reticulum and mitochondria and occurring
      free within the cytoplasm. There was no significant effect of HIV on Flt-1 and
      sFlt-1 immunoexpression in both exchange and stem villi. A significant effect of
      type of pregnancy (normotensive vs pre-eclamptic) on Flt-1 and sFlt-1
      immunoexpression (p = 0.003) within exchange rather than stem villi, indicated
      that the pre-eclamptic had elevated Flt-1 and sFlt-1 expressions compared to the
      normotensive pregnant women. There was no interaction between HIV and pregnancy
      type (normotensive vs pre-eclampsia) for Flt-1 and sFlt-1 expressions in both
      exchange and stem villi. A weak correlation of Flt-1 and sFlt-1 intensity between
      the exchange and stem villi was noted. DISCUSSION: Elevated immunoexpression of
      Flt-1 and sFlt-1 within trophoblasts suggests an autocrine mode of action on
      trophoblast invasion and differentiation thereby contributing to abnormal
      placentation with consequential endothelial dysfunction in pre-eclampsia.
      CONCLUSION: Irrespective of the HIV status, placental Flt-1 and sFlt-1
      expressions remain elevated in pre-eclampsia compared to normotensive
      pregnancies.

PMID- 24880211
TI  - Accuracy of perioperative mandibular positions in orthognathic surgery.
AB  - Mandibular position is an important parameter used for the diagnosis of
      dentofacial deformities, as well as for orthognathic surgery planning and
      execution. Centric relation (anterior and superior relationship of the mandibular
      condyles interposed by the thinnest portion of their disks against the articular
      eminencies), centric occlusion (when lower teeth contact upper teeth at centric
      relation), and maximal intercuspation (complete interdigitation of lower and
      upper teeth) are not often addressed as factors that influence the results of
      orthognathic surgery, although these relationships are critical to ensure
      accuracy during the surgery. The present study assessed occlusal measurements
      taken before and after the induction of general anaesthesia from consecutive
      orthognathic surgery subjects. The variables assessed included the differences
      between these occlusal measurements, patient age, gender, type of deformity, and
      type of proposed orthognathic surgical procedure. The results demonstrated
      statistically significant differences for mandibular retrusion from maximal
      intercuspation to centric occlusion position, whereas the mandible appeared not
      to change significantly from centric occlusion after the induction of general
      anaesthesia. Patient age and the type of deformity appeared to influence the
      results. While in most instances centric occlusion can be adequately reproduced
      under general anaesthesia, for some specific orthognathic cases more accurate
      results might be obtained if the mandible-first sequence is used. 

PMID- 24880212
TI  - Long-term cosmetic outcomes and toxicities of proton beam therapy compared with
      photon-based 3-dimensional conformal accelerated partial-breast irradiation: a
      phase 1 trial.
AB  - PURPOSE: To present long-term outcomes of a prospective feasibility trial using
      either protons or 3-dimensional conformal photon-based (accelerated partial
      breast irradiation [APBI]) techniques. METHODS AND MATERIALS: From October 2003
      to April 2006, 98 evaluable patients with stage I breast cancer were treated with
      APBI (32 Gy in 8 fractions given twice daily) on a prospective clinical trial: 19
      with proton beam therapy (PBT) and 79 with photons or mixed photons/electrons.
      Median follow-up was 82.5 months (range, 2-104 months). Toxicity and patient
      satisfaction evaluations were performed at each visit. RESULTS: At 7 years, the
      physician rating of overall cosmesis was good or excellent for 62% of PBT
      patients, compared with 94% for photon patients (P=.03). Skin toxicities were
      more common for the PBT group: telangiectasia, 69% and 16% (P=.0013);
      pigmentation changes, 54% and 22% (P=.02); and other late skin toxicities, 62%
      and 18% (P=.029) for PBT and photons, respectively. There were no significant
      differences between the groups in the incidences of breast pain, edema, fibrosis,
      fat necrosis, skin desquamation, and rib pain or fracture. Patient-reported
      cosmetic outcomes at 7 years were good or excellent for 92% and 96% of PBT and
      photon patients, respectively (P=.95). Overall patient satisfaction was 93% for
      the entire cohort. The 7-year local failure rate for all patients was 6%, with 3
      local recurrences in the PBT group (7-year rate, 11%) and 2 in photon-treated
      patients (4%) (P=.22). CONCLUSIONS: Local failure rates of 3-dimensional APBI and
      PBT were similar in this study. However, PBT, as delivered in this study, led to
      higher rates of long-term telangiectasia, skin color changes, and skin
      toxicities. We recommend the use of multiple fields and treatment of all fields
      per treatment session or the use of scanning techniques to minimize skin
      toxicity.

PMID- 24880213
TI  - Patterns across multiple memories are identified over time.
AB  - Memories are not static but continue to be processed after encoding. This is
      thought to allow the integration of related episodes via the identification of
      patterns. Although this idea lies at the heart of contemporary theories of
      systems consolidation, it has yet to be demonstrated experimentally. Using a
      modified water-maze paradigm in which platforms are drawn stochastically from a
      spatial distribution, we found that mice were better at matching platform
      distributions 30 d compared to 1 d after training. Post-training time-dependent
      improvements in pattern matching were associated with increased sensitivity to
      new platforms that conflicted with the pattern. Increased sensitivity to pattern
      conflict was reduced by pharmacogenetic inhibition of the medial prefrontal
      cortex (mPFC). These results indicate that pattern identification occurs over
      time, which can lead to conflicts between new information and existing knowledge
      that must be resolved, in part, by computations carried out in the mPFC. 

PMID- 24880214
TI  - Leptin signaling in astrocytes regulates hypothalamic neuronal circuits and
      feeding.
AB  - We found that leptin receptors were expressed in hypothalamic astrocytes and that
      their conditional deletion led to altered glial morphology and synaptic inputs
      onto hypothalamic neurons involved in feeding control. Leptin-regulated feeding
      was diminished, whereas feeding after fasting or ghrelin administration was
      elevated in mice with astrocyte-specific leptin receptor deficiency. These data
      reveal an active role of glial cells in hypothalamic synaptic remodeling and
      control of feeding by leptin. 

PMID- 24880215
TI  - Functional organization of glomerular maps in the mouse accessory olfactory bulb.
AB  - The mammalian accessory olfactory system extracts information about species, sex
      and individual identity from social odors, but its functional organization
      remains unclear. We imaged presynaptic Ca(2+) signals in vomeronasal inputs to
      the accessory olfactory bulb (AOB) during peripheral stimulation using light
      sheet microscopy. Urine- and steroid-responsive glomeruli densely innervated the
      anterior AOB. Glomerular activity maps for sexually mature female mouse urine
      overlapped maps for juvenile and/or gonadectomized urine of both sexes, whereas
      maps for sexually mature male urine were highly distinct. Further spatial
      analysis revealed a complicated organization involving selective juxtaposition
      and dispersal of functionally grouped glomerular classes. Glomeruli that were
      similarly tuned to urines were often closely associated, whereas more disparately
      tuned glomeruli were selectively dispersed. Maps to a panel of sulfated steroid
      odorants identified tightly juxtaposed groups that were disparately tuned and
      dispersed groups that were similarly tuned. These results reveal a modular,
      nonchemotopic spatial organization in the AOB. 

PMID- 24880216
TI  - Identification of distinct ChAT+ neurons and activity-dependent control of
      postnatal SVZ neurogenesis.
AB  - Postnatal and adult subventricular zone (SVZ) neurogenesis is believed to be
      primarily controlled by neural stem cell (NSC)-intrinsic mechanisms, interacting
      with extracellular and niche-driven cues. Although behavioral experiments and
      disease states have suggested possibilities for higher level inputs, it is
      unknown whether neural activity patterns from discrete circuits can directly
      regulate SVZ neurogenesis. We identified a previously unknown population of
      choline acetyltransferase (ChAT)(+) neurons residing in the rodent SVZ neurogenic
      niche. These neurons showed morphological and functional differences from
      neighboring striatal counterparts and released acetylcholine locally in an
      activity-dependent fashion. Optogenetic inhibition and stimulation of
      subependymal ChAT(+) neurons in vivo indicated that they were necessary and
      sufficient to control neurogenic proliferation. Furthermore, whole-cell
      recordings and biochemical experiments revealed direct SVZ NSC responses to local
      acetylcholine release, synergizing with fibroblast growth factor receptor
      activation to increase neuroblast production. These results reveal an unknown
      gateway connecting SVZ neurogenesis to neuronal activity-dependent control and
      suggest possibilities for modulating neuroregenerative capacities in health and
      disease. 

PMID- 24880218
TI  - Results of surgical treatment of cervical spondylotic myelopathy in patients aged
      75 years or more: a comparative study of operative methods.
AB  - INTRODUCTION: The number of surgical procedures in elderly patients has been
      increasing as the population has grown older; recently, spine surgeons have been
      more likely to encounter elderly patients with cervical myelopathy in need of
      surgical treatment. There are many reports about surgical treatment of elderly
      patients with cervical spondylotic myelopathy (CSM); however, there are no
      studies about the proper selection of surgical methods and comparison of their
      results in CSM patients aged >= 75 years. The objective of this study was to
      review the results of operative methods in CSM patients aged >= 75 years.
      METHODS: Forty-three consecutive cases with an average age of 79 years that
      underwent surgical treatment were included in this study. The neurological
      severity was assessed using the Japanese Orthopaedic Association score for
      cervical myelopathy (JOA). The JOA scores were evaluated before surgery and at
      final follow-up. There were 21 laminoplasty procedures (from C3 to C7), 13
      selective laminoplasty procedures (one above and one below the affected
      intervertebral level), and nine anterior decompression and fusion procedures. A
      selective laminoplasty was performed in cases with general complications and was
      diagnosed as one intervertebral level both clinically and electrophysiologically.
      Surgical results were compared among the three treatment groups. RESULTS: The
      average preoperative JOA score was 7.7 points and the average JOA recovery rate
      was 45 %. There were three cases of C5 palsy and one wound infection. Operative
      time and intraoperative bleeding in the selective laminoplasty group were
      significantly smaller than those in the other groups. There was no significant
      difference in the JOA recovery rates among the groups. CONCLUSIONS: Selective
      laminoplasty is less invasive and the surgical results in our study were almost
      good. It also has good short-term results. However, the indication for surgery
      has to be selected carefully in elderly CSM patients.

PMID- 24880217
TI  - Two distinct layer-specific dynamics of cortical ensembles during learning of a
      motor task.
AB  - The primary motor cortex (M1) possesses two intermediate layers upstream of the
      motor-output layer: layer 2/3 (L2/3) and layer 5a (L5a). Although repetitive
      training often improves motor performance and movement coding by M1 neuronal
      ensembles, it is unclear how neuronal activities in L2/3 and L5a are reorganized
      during motor task learning. We conducted two-photon calcium imaging in mouse M1
      during 14 training sessions of a self-initiated lever-pull task. In L2/3, the
      accuracy of neuronal ensemble prediction of lever trajectory remained unchanged
      globally, with a subset of individual neurons retaining high prediction accuracy
      throughout the training period. However, in L5a, the ensemble prediction accuracy
      steadily improved, and one-third of neurons, including subcortical projection
      neurons, evolved to contribute substantially to ensemble prediction in the late
      stage of learning. The L2/3 network may represent coordination of signals from
      other areas throughout learning, whereas L5a may participate in the evolving
      network representing well-learned movements. 

PMID- 24880219
TI  - On the role of low-permeability beds in the acquisition of F and SO4
      concentrations in a multi-layer aquifer, South-West France.
AB  - Fluoride (F(-)) commonly threatens groundwater quality. This is the case around
      the city of Bordeaux (France), where numerous wells tapping the thick and complex
      Eocene aquifer are contaminated by fluoride, which presents an issue for drinking
      water supply. The joint analysis of the spatial distribution of fluoride with
      other species like sulfate suggests that concentrations are mainly related to the
      occurrence of low-permeability layers containing evaporites or fluorite deposits.
      In order to identify the origin of the observed concentrations, a radial flow and
      transport model is implemented at the borehole scale. The hydraulic conductivity
      of the low-permeability layers and the vertical dispersivity of the aquifer were
      optimized to match the observed values of sulfate and fluoride concentrations.
      Interestingly, each of these parameters influences differently the simulated
      concentrations. This model has been successfully implemented to a neighboring
      well with the same parameter values, which tests the approach. The major
      conclusions drawn are: (i) the contamination in fluoride originates from the low
      permeability layers, (ii) every low-permeability layer intercepted by the well
      releases fluoride (iii) Contamination not only originates from pore water of low
      permeability layers, but may persist with long-term pumping due to mineral
      dissolution. As a consequence, fluoride contamination is likely to persist for a
      long time and the only solution to reduce fluoride concentration in abstracted
      water is to seal well screens facing low-permeability layers. 

PMID- 24880220
TI  - Simultaneous determination of 1-beta-d-Arabinofuranosylcytosine and two
      metabolites, 1-beta-d-Arabinofuranosyluracil and 1-beta-d
      Arabinofuranosylcytosine triphosphate in leukemic cell by HPLC-MS/MS and the
      application to cell pharmacokinetics.
AB  - A specific and reliable HPLC-MS/MS method was developed and validated for the
      simultaneous determination of 1-beta-d-Arabinofuranosylcytosine (ara-C), 1-beta-d
      Arabinofuranosyluracil (ara-U) and 1-beta-d-Arabinofuranosylcytosine triphosphate
      (ara-CTP) in the leukemic cells for the first time. The analytes were separated
      on a C18 column (100mm*2.1mm, 1.8MUm) and a triple-quadrupole mass spectrometry
      equipped with an electrospray ionization (ESI) source was used for detection. The
      ion-pairing reagent, NFPA, was added to the mobile phase to retain the analytes
      in the column. The cell homogenates sample was prepared by the simple protein
      precipitation. The calibration curves were linear over a concentration range of
      3.45-3450.0ng/mL for ara-C, 1.12-1120.0ng/mL for ara-U and 4.13-4130.0ng/mL for
      ara-CTP. The intra-day and inter-day precision was less than 15% and the relative
      error (RE) were all within +/-15%. The validated method was successfully applied
      to assess the disposition characteristics of ara-C and support cell
      pharmacokinetics after the patients with leukemia were intravenously infused with
      SDAC and HiDAC. The result of the present study would provide the valuable
      information for the ara-C therapy. 

PMID- 24880221
TI  - Ecosystem-based management of a Mediterranean urban wastewater system: a
      sensitivity analysis of the operational degrees of freedom.
AB  - Urban wastewater systems discharge organic matter, nutrients and other pollutants
      (including toxic substances) to receiving waters, even after removing more than
      90% of incoming pollutants from human activities. Understanding their
      interactions with the receiving water bodies is essential for the implementation
      of ecosystem-based management strategies. Using mathematical modeling and
      sensitivity analysis we quantified how 19 operational variables of an urban
      wastewater system affect river water quality. The mathematical model of the
      Congost system (in the Besos catchment, Spain) characterizes the dynamic
      interactions between sewers, storage tanks, wastewater treatment plants and the
      river. The sensitivity analysis shows that the use of storage tanks for peak
      shaving and the use of a connection between two neighboring wastewater treatment
      plants are the most important factors influencing river water quality. We study
      how the sensitivity of the water quality variables towards changes in the
      operational variables varies along the river due to discharge locations and river
      self-purification processes. We demonstrate how to use the approach to identify
      interactions and how to discard non-influential operational variables. 

PMID- 24880223
TI  - Balancing cognitive control: how observed movements influence motor performance
      in a task with balance constraints.
AB  - We investigated the influence of observed movements on executed movements in a
      task requiring lifting one foot from the floor while maintaining whole-body
      balance. Sixteen young participants (20-30 years) performed foot lift movements,
      which were either cued symbolically by a letter (L/R, indicating to lift the
      left/right foot) or by a short movie showing a foot lift movement. In the symbol
      cue condition, stimuli from the movie cue condition were used as distractors, and
      vice versa. Anticipatory postural adjustments (APAs) and actual foot lifts were
      recorded using force plates and optical motion capture. Foot lift responses were
      generally faster in response to the movie compared to the symbol cue condition.
      Moreover, incongruent movement distractors interfered with performance in the
      symbol cue condition, as shown by longer response times and increased number of
      APAs. Latencies of the first (potentially wrong) APA in a trial were shorter for
      movie compared to symbol cues but were not affected by cue-distractor congruency.
      Amplitude of the first APA was smaller when it was followed by additional APAs
      compared to trials with a single APA. Our results show that automatic imitation
      tendencies are integrated with postural control in a task with balance
      constraints. Analysis of the number, timing and amplitude of APAs indicates that
      conflicts between intended and observed movements are not resolved at a purely
      cognitive level but directly influence overt motor performance, emphasizing the
      intimate link between perception, cognition and action.

PMID- 24880222
TI  - Amyloid fibrils nucleated and organized by DNA origami constructions.
AB  - Amyloid fibrils are ordered, insoluble protein aggregates that are associated
      with neurodegenerative conditions such as Alzheimer's disease. The fibrils have a
      common rod-like core structure, formed from an elongated stack of beta-strands,
      and have a rigidity similar to that of silk (Young's modulus of 0.2-14 GPa). They
      also exhibit high thermal and chemical stability and can be assembled in vitro
      from short synthetic non-disease-related peptides. As a result, they are of
      significant interest in the development of self-assembled materials for
      bionanotechnology applications. Synthetic DNA molecules have previously been used
      to form intricate structures and organize other materials such as metal
      nanoparticles and could in principle be used to nucleate and organize amyloid
      fibrils. Here, we show that DNA origami nanotubes can sheathe amyloid fibrils
      formed within them. The fibrils are built by modifying the synthetic peptide
      fragment corresponding to residues 105-115 of the amyloidogenic protein
      transthyretin and a DNA origami construct is used to form 20-helix DNA nanotubes
      with sufficient space for the fibrils inside. Once formed, the fibril-filled
      nanotubes can be organized onto predefined two-dimensional platforms via DNA-DNA
      hybridization interactions.

PMID- 24880224
TI  - Visual recognition memory enhancement in children through differential outcomes.
AB  - OBJECTIVE: The use of differential outcomes has been shown to enhance
      discriminative learning and face recognition in children and adults. In this
      study, we further investigated whether the differential outcome procedure (DOP)
      would also be effective in improving recognition memory for a wide range of
      stimuli with varying visual complexity (familiar objects, abstract stimuli, and
      complex scenes) in 5- and 7-year-old children. METHOD: Participants viewed a
      sample stimulus and, after a short (5s) or a long (15s) delay, they had to
      identify the previously seen stimulus among four choice alternatives. In the
      differential outcomes condition, each sample stimulus was paired with a specific
      outcome; whereas in the non-differential conditions outcomes were administered
      randomly. In Experiment 2, we replicated Experiment 1 but in addition we asked
      participants to perform an articulatory suppression task to prevent verbal
      rehearsal. RESULTS: Children showed a greater overall visual delayed recognition
      when differential outcomes were arranged in both experiments. The type of
      stimulus being used modulated this effect; a beneficial effect of the
      differential outcomes training was evident with abstract objects in Experiment 1
      and with both, abstract objects and scenes in Experiment 2.

PMID- 24880225
TI  - Immediate emotion-enhanced memory dependent on arousal and valence: the role of
      automatic and controlled processing.
AB  - The phenomenon that emotional stimuli are better remembered than neutral ones is
      called emotion-enhanced memory (EEM). Previous studies have shown that both
      valence and arousal of stimuli contributed to EEM. Kensinger and Corkin (2004)
      proposed that the EEM dependent on arousal was associated with automatic encoding
      processes, whereas the EEM dependent on valence was associated with controlled
      encoding processes. Their experiment with negative words provided some evidence
      for this associative pattern. However, it is unclear whether the observed
      association that occurred with negative emotional stimuli could be replicated
      with positive emotional stimuli. To further examine this issue, two experiments
      were conducted to investigate the immediate EEM of emotional words in three
      different attention conditions using a divided attention (DA) paradigm. Results
      indicated that the immediate EEM dependent on valence was associated with
      controlled processing, while the immediate EEM dependent on arousal was not
      always associated with automatic processing. The immediate EEM dependent on
      arousal for negative stimuli was associated with automatic processing, whereas
      the immediate EEM dependent on arousal for positive stimuli was associated with
      controlled processing. Therefore, the immediate EEM dependent on arousal, whether
      it is associated with automatic or controlled processing, is moderated by the
      valence of stimuli. 

PMID- 24880226
TI  - Modified high-intensity interval training increases peak cardiac power output in
      patients with heart failure.
AB  - PURPOSE: Although high-intensity interval aerobic training (HIT) effectively
      improves aerobic fitness, the risk of cardiac arrest transiently increases during
      strenuous physical exertion in patients with cardiovascular disease. For safety
      and efficacy concerns, this investigation explored the effect of a modified HIT
      (mHIT) on exertional ventilatory-hemodynamic efficiency in heart failure patients
      with reduced ejection fraction (HFREF). METHODS: HFREF patients were
      prospectively assigned to two groups: mHIT and usual healthcare (UC). The former
      comprised supervised continuous aerobic training at ventilatory anaerobic
      threshold for 50 min/day, 3 days/week for 4 weeks, and then 3-min intervals at 40
      and 80% VO2 reserve for 50 min/day, 3 days/week for 8 weeks. The latter received
      optimal medical treatment only. Ventilatory and hemodynamic responses during
      exercise were measured before and after the intervention. Paired-t and repeated
      measures ANOVA with post hoc tests were adopted. RESULTS: Each group had an N of
      33. The mHIT and UC group had matched baseline characteristics including health
      promotion concept and behavior score. The mHIT for 12 weeks (1) increased VO2,
      cardiac output, and notably, cardiac power output at peak workload (1,151 +/- 573
      vs. 1,306 +/- 596 L/min/mmHg); (2) reduced V E/VO2 (32.4 +/- 4.6 vs. 30.0 +/-
      4.0), breathing frequency, ventilation, and enhanced stroke volume compliance at
      identical submaximal intensity (50% peak workload at pre-intervention
      evaluation). No significant changes in ventilatory and hemodynamic responses to
      exercise were observed following the UC. CONCLUSIONS: The mHIT regimen improves
      peak cardiac pumping capacity with reducing cardiac after-load and simultaneously
      increases ventilation efficiency during exercise in patients with HFREF. Thereby,
      aerobic fitness is ameliorated.

PMID- 24880228
TI  - Effect of pH and temperature upon self-assembling process between poly(aspartic
      acid) and Pluronic F127.
AB  - The present investigation was made in order to evaluate the capability of self
      assembling of the two water soluble polymers, respectively, poly(aspartic acid)
      and Pluronic F127 into well interpenetrated mixture, and to evidence the
      connection effects intervened during polymer complex formation to exhibit good
      stability once formed, as well to understand and correlate the binding strength
      and the interval between better association domains. The effect of pH and
      temperature on the interpolymeric complex formation between poly(aspartic acid)
      and Pluronic F127 was studied by combining rheology with light scattering
      technique. The solution mixtures between poly(aspartic acid) and Pluronic F127
      are Newtonian fluids for all ratios among them. Depending on the polymeric
      mixture composition and experimental temperature, positive or negative deviations
      of the experimental values from the additive dependence appear. An interesting
      behavior was registered around 1/1 wt. ratio between the two polymers, when the
      hydrodynamic diameter of the interpenetrated polymeric particles decreased
      suddenly. This allows us to conclude the formation of core-shell micelle
      structure with poly(aspartic acid) core and Pluronic F127 as shell, performed
      through strong interactions between polymers. This behavior was sustained by the
      increase of absolute value of zeta potential owing to the decrease of functional
      groups number at the surface of micelles.

PMID- 24880227
TI  - Stroke prevention in atrial fibrillation: established oral anticoagulants versus
      novel anticoagulants-translating clinical trial data into practice.
AB  - Anticoagulation for stroke prevention in atrial fibrillation (AF) is effective.
      Pivotal trials RE-LY, ROCKET AF, ARISTOTLE, and ENGAGE-AF TIMI 48 tested novel
      agents against warfarin (W). In RE-LY, an open-label trial, dabigatran 150 mg BID
      (D150) was superior (35%) and 110 mg BID (D110) was noninferior to W. D150
      reduced ischemic strokes by 25% and intracerebral bleeds by 74%, but increased
      major GI bleeds by 0.5 % per year. In ROCKET AF, a double-blind study,
      rivaroxaban 20 mg daily, downtitrated to 15 mg daily (if CrCl was <49) was
      noninferior for efficacy and safety, with an increase in GI bleeds. In ARISTOTLE,
      a double-blind study, apixaban 5 mg BID (downtitrated to 2.5 mg BID if two of the
      following were present: age, >80; weight, <60 kg; or serum creatinine, >1.5 mg)
      was superior for safety (31%), efficacy (21%), and all-cause mortality (11%). In
      ENGAGE-AF TIMI 48, edoxaban 60 mg once daily (30 mg once daily if CrCl 30-50
      ml/min, weight <60 kg, or concomitant verapamil or quinidine) was noninferior to
      W for efficacy, but reduced major bleeding (20%). To translate clinical trials to
      practice, understanding the disease and each anticoagulant is essential. For all
      novel agents, rapid anticoagulation, absence of monitoring, and a short half-life
      differentiate them from W. Bleed rates were either noninferior or lower than for
      W, without an antidote. Patient compliance is critical. Knowledge of renal
      function is essential and maintaining patients on therapy is key.

PMID- 24880229
TI  - Endosomal pH responsive polymers for efficient cancer targeted gene therapy.
AB  - Treatment of human diseases at gene level is always limited by effective gene
      delivery vectors. In this study, we designed and developed an endosomal pH
      sensitive targeted gene delivery system, folic acid functionalized Schiff-base
      linked imidazole chitosan (FA-SLICS), for cancer therapy. The FA-SLICS is able to
      self-assemble plasmid DNA (pDNA) into nano-scaled polyplexes under a neutral
      condition and to release the loaded pDNA in the endosomal microenvironment due to
      the presence of pH sensitive Schiff-base moieties along chitosan backbones. The
      FA-SLICS has negligible cytotoxicity to normal cells (CHO), but displays slight
      toxicity to cancer cells (HeLa and HepG2). In addition, FA-SLICS can selectively
      and efficiently transfect FR (folate receptor) positive cells (HeLa cells) as a
      gene carrier. Therefore, the FA-SLICS should be a promising delivery vector in
      cancer gene therapy based on its cell targeting capability and intracellular
      microenvironment controlled delivery mechanism. 

PMID- 24880230
TI  - Synthesis and anticancer activity of gamma-(triazolyl ethylidene)butenolides and
      polyfunctional pyrrolinones.
AB  - A series of novel gamma-(triazolyl ethylidene)butenolides (4-23) were prepared
      from commercially available l-ascorbic acid in good yields. These butenolides on
      reaction with ethanolic ammonia/amines led to formation of respective 5-hydroxy
      pyrrolinones (24-33). The two of these pyrrolinones on dehydration with p
      toluenesulfonic acid, were transformed into gamma-(triazolyl
      ethylidene)pyrrolinones (34, 35). Among all the newly synthesized hybrid
      molecules tested for anticancer activity in vitro, compounds 24, 25, 26, 27, 28,
      30 and 32 showed significant activity against MCF-7, MDA-MB-231, PC-3 or U-937
      cells. In particular compound 25 (IC50 = 11.3 MUM) exhibited most potent activity
      against breast cancer cells and preliminary studies revealed that potency of this
      compound is due to ROS generation, subsequent activation of p38, leading to
      apoptosis and inhibition of cancer cells.

PMID- 24880231
TI  - Group A streptococcus inhibitors by high-throughput virtual screening.
AB  - Group A streptococcus (GAS) is a Gram-positive bacterium, which can cause
      multiple types of disease from mild infections of skin and throat to invasive and
      life-threatening infections. Recently RNase J1 and J2 were found to be essential
      for the growth of GAS. In order to identify inhibitors against RNase J1/J2,
      homology models of both the ligand-free apo-form and the ligand-bound holo-form
      complexes were constructed as templates for high-throughput virtual screening
      (HTVS). A focused small molecule library and the commercially available Maybridge
      database were employed as sources for potential inhibitors. A cell-based
      biological assay identified two compounds with 10 MUM MIC activity.

PMID- 24880232
TI  - Inhibition of Enterococcus faecalis biofilm formation by highly active lactones
      and lactams analogues of rubrolides.
AB  - Seven beta-aryl substituted gamma-alkylidene-gamma-lactones analogues of
      rubrolides were synthesized from mucobromic acid and converted through a
      lactamization with isobutylamine into their corresponding gamma-hydroxy-gamma
      lactams (76-85%). These lactams were converted into (Z)- and (E)-gamma-alkylidene
      gamma-lactams (23-45%). All compounds were fully characterized by IR, NMR ((1)H
      and (13)C), COSY and HETCOR bidimensional experiments, and NOE difference
      spectroscopy experiments when necessary. Evaluation of these three different
      classes of compounds against Enterococcus faecalis biofilm formation showed that
      all classes are active and the highest biofilm inhibition activity was caused by
      lactam 13f (IC50 = 0.76 MUg/mL). Moreover, in almost all cases at least one of
      the lactams is more active than its correspondent gamma-alkylidene-gamma-lactone.
      The use of rubrolides as a lead structure has proven successful for the
      identification of new compounds displaying novel antibacterial activities, namely
      biofilm inhibition, which have the potential for the development of antimicrobial
      drugs targeted to inhibition of the initial stages of bacterial infections,
      rather than bacterial viability. Such drugs are less prompt to induce bacterial
      resistance, being therefore a more cost-effective investment for pharmaceutical
      research.

PMID- 24880233
TI  - A case of cerebellar hemangioblastoma with rhabdoid features.
AB  - We present an unusual case of cerebellar hemangioblastoma characterized by
      rhabdoid features. The patient was a 35-year-old Japanese man with occipital
      neuralgia and exacerbating blurred vision. Magnetic resonance imaging revealed a
      left posterior cranial fossa tumor, which was isointense on T1-weighted images
      and hyperintense on T2-weighted images with marked homogeneous enhancement.
      Histology of the surgically resected tumor showed cellular-type hemangioblastoma
      with extensive proliferation of rhabdoid cells Immunohistochemistry analysis
      showed tumor cells positive for inhibin A, CD56, vimentin, INI-1, and vascular
      endothelial growth factor; negative for PAX8, CD10, epithelial membrane antigen,
      cytokeratin, (AE1/3), alpha-smooth muscle actin and D2-40; and had focal
      positivity for glial fibrillary acidic protein and S100. The Ki-67 labeling index
      was <1 %. Ultrastructural analysis revealed large lipid droplets and abundant
      intracellular accumulation of intermediate filaments. Based on these findings,
      the diagnosis was hemangioblastoma with focal rhabdoid features. After a 14-month
      follow-up, there was no evidence of recurrence. This is the first report of
      hemangioblastoma with rhabdoid features in the central nervous system. In
      addition, we discuss the possible pathogenesis. 

PMID- 24880234
TI  - Food environment, walkability, and public open spaces are associated with
      incident development of cardio-metabolic risk factors in a biomedical cohort.
AB  - We investigated whether residential environment characteristics related to food
      (unhealthful/healthful food sources ratio), walkability and public open spaces
      (POS; number, median size, greenness and type) were associated with incidence of
      four cardio-metabolic risk factors (pre-diabetes/diabetes, hypertension,
      dyslipidaemia, abdominal obesity) in a biomedical cohort (n=3205). Results
      revealed that the risk of developing pre-diabetes/diabetes was lower for
      participants in areas with larger POS and greater walkability. Incident abdominal
      obesity was positively associated with the unhealthful food environment index. No
      associations were found with hypertension or dyslipidaemia. Results provide new
      evidence for specific, prospective associations between the built environment and
      cardio-metabolic risk factors. 

PMID- 24880235
TI  - Effect of pulsed electric field treatments on permeabilization and extraction of
      pigments from Chlorella vulgaris.
AB  - The effect of pulsed electric field (PEF) treatments of different intensities on
      the electroporation of the cytoplasmatic membrane of Chlorella vulgaris, and on
      the extraction of carotenoids and chlorophylls were investigated. Staining the
      cells with propidium iodide before and after the PEF treatment revealed the
      existence of reversible and irreversible electroporation. Application of PEF
      treatments in the range of 20-25 kV cm(-1) caused most of the population of C.
      vulgaris to be irreversibly electroporated even at short treatment times (5
      pulses of 3 us). However, at lower electric field strengths (10 kV cm(-1)), cells
      that were reversibly electroporated were observed even after 50 pulses of 3 us.
      The electroporation of C. vulgaris cells by PEF higher than 15 kV cm(-1) and
      duration is higher than 15 us increased significantly the extraction yield of
      intracellular components of C. vulgaris. The application of a 20 kV cm(-1) for 75
      MUs increased the extraction yield just after the PEF treatment of the
      carotenoids, and chlorophylls a and b 0.5, 0.7, and 0.8 times, respectively.
      However, further increments in electric field strength and treatment time did not
      cause significant increments in the extraction yield. The extraction of
      carotenoids from PEF-treated C. vulgaris cells after 1 h of the application of
      the treatment significantly increased the extraction yield in comparison to the
      yield obtained from the cells extracted just after the PEF treatment. After PEF
      treatment at 20 kV cm(-1) for 75 us, extraction yield for carotenoids, and
      chlorophylls a and b increased 1.2, 1.6, and 2.1 times, respectively. A high
      correlation was observed between irreversible electroporation and percentage of
      yield increase when the extraction was conducted after 1 h of the application of
      PEF treatment (R: 0.93), but not when the extraction was conducted just after PEF
      treatment (R: 0.67).

PMID- 24880236
TI  - Maintenance of radiographic correction at 2 years following lumbar pedicle
      subtraction osteotomy is superior with upper thoracic compared with thoracolumbar
      junction upper instrumented vertebra.
AB  - PURPOSE: The goal of this study was to characterize the spino-pelvic realignment
      and the maintenance of that realignment by the upper-most instrumented vertebra
      (UIV) for adult deformity spinal (ASD) patients treated with lumbar pedicle
      subtraction osteotomy (PSO). METHODS: ASD patients were divided by UIV,
      classified as upper thoracic (UT: T1-T6) or Thoracolumbar (TL: T9-L1).
      Complications were recorded and radiographic parameters included thoracic
      kyphosis (TK, T2-T12), lumbar lordosis (LL, L1-S1), sagittal vertical axis (SVA),
      pelvic tilt, and the mismatch between pelvic incidence and LL. Patients were also
      classified by the Scoliosis Research Society (SRS)-Schwab modifier grades.
      Changes in radiographic parameters and SRS-Schwab grades were evaluated between
      the two groups. Additional analyses were performed on patients with pre-operative
      SVA >= 15 cm. RESULTS: 165 patients were included (UT: 81 and TL: 84); 124 women,
      41 men, with average age 59.9 +/- 11.1 years (range 25-81). UT had a lower
      percentage of patients above the radiographic thresholds for disability than TL.
      UT had a significantly higher percentage of patients that improved in SRS-Schwab
      global alignment grade than the TL group at 2 years. Within the patients with pre
      operative SVA >= 15 cm, TL developed significantly increased SVA and had a
      significantly higher percentage of patients above the SVA threshold at 3 months,
      and 1 and 2 years than UT. CONCLUSIONS: Patients undergoing a single-level PSO
      for ASD who have fixation extending to the UT region (T1-T6) are more likely to
      maintain sagittal spino-pelvic alignment, lower overall revision rates and
      revision rate for proximal junctional kyphosis than those with fixation
      terminating in the TL region (T9-L1).

PMID- 24880238
TI  - Anti-Trichomonas vaginalis activity from triterpenoid derivatives.
AB  - Trichomonas vaginalis is a flagellated parasite that causes trichomonosis, the
      most common non-viral sexually transmitted disease (STD) in the world.
      Worryingly, trichomonosis is associated to increased transmission of HIV. Due to
      high frequency of the infection during pregnancy and the development of
      metronidazole-resistant isolates, therapeutic alternatives to 5-nitroimidazole
      are being searched. Triterpenes are natural products presenting several
      biological activities such as anti-protozoal activity. The aim of this study was
      to evaluate the in vitro anti-T. vaginalis activity from betulinic and ursolic
      acids, as well as semisynthetic derivatives obtained. Compounds obtained from
      betulinic acid presented better activity than those from ursolic acid. Piperazine
      derivatived from betulinic acid presented minimum inhibitory concentration (MIC)
      value of 91.2 MUM, and the kinetic growth curve performed with parasites treated
      with this most active compound revealed complete inhibition of trophozoite
      proliferation at 2 h of incubation and total abolition of trophozoite growth in
      24 h, revealing that the piperazine derivative is an efficient trichomonacidal
      molecule. The same compound promoted total erythrocyte lysis and lactate
      dehydrogenase (LDH) liberation of 83 and 100% (at 45.6 and 91.2 MUM,
      respectively), indicating parasite membrane damage. The piperazine derivative
      demonstrated cytotoxic effect against the HMVII and HeLa cell lineages at the MIC
      value. This is the first report of semisynthetic triterpenoid derivatives with
      anti-T. vaginalis activity, revealing the high potential of these compounds as
      trichomonacidal agents.

PMID- 24880237
TI  - Phylogenetic relationships between pinworms (Nematoda: Enterobiinae) parasitising
      the critically endangered orang-utan, according to the characterisation of
      molecular genomic and mitochondrial markers.
AB  - Pinworms (Nematoda: Enterobiinae) include 52 species parasitising primates
      throughout the world. In the present study, we performed the first ever molecular
      analysis to investigate the phylogenetic position of recently described pinworms
      parasitising the Sumatran orang-utan. The phylogenetic analysis of mitochondrial
      CO1 and chromosomal 18S rDNA and ITS1 regions could support the independent
      status of several Nematoda species. Our molecular data clearly suggest that
      Enterobius (Colobenterobius) buckleyi and Lemuricola (Protenterobius) pongoi
      together with Pongobius hugoti form separate clades among other studied species,
      which significantly supports the hypothesis of recently described new species
      parasitising the orang-utan (Pongo abelii and Pongo pygmaeus). The phylogenetic
      tree based on cytochrome oxidase 1 (CO1) gene variability showed possible close
      relationships between L. (Protenterobius) pongoi and P. hugoti; thus, we can
      assume that these species could have initially diverged in sympatry from a common
      ancestor. 

PMID- 24880239
TI  - Effects of in vitro conditions on the survival of Alaria alata mesocercariae.
AB  - The aim of this study was to determine the effect of different concentrations of
      table salt (NaCl) and ethanol (v/v) solutions on the viability of Alaria alata
      mesocercariae. Furthermore, the survival of A. alata mesocercariae during
      simulated human gastric digestion was evaluated. For this purpose, A. alata
      mesocercariae migration technique (AMT) was used for the isolation of the
      parasite from high-positive A. alata mesocercariae meat from wild boar, raccoon,
      raccoon dog, and badger meat. In total, we have studied the behavior of 582
      larvae under different conditions (NaCl, ethanol, and artificial gastric juice)
      in three independent in vitro experiments. The larvae survived at a NaCl
      concentration of up to 2.0% until day 21 with a median survival time of 11 days.
      At 3.0% NaCl concentration, the larvae lost their vitality after less than 24 h.
      In addition, it was found that ethanol concentrations from 8.0 to 70.0% were
      effective at reducing survival of A. alata mesocercariae within a short period of
      time (<1 min). Finally, our studies have revealed that it required 120 min to
      reliably inactivate all A. alata mesocercariae within HCl-pepsin digestion
      solution with a pH of 1.5-2.0 at 37 degrees C. Consequently, the results showed
      that 3.0% is the minimum concentration of NaCl in meat products recommended for
      human consumption because at lower NaCl concentration the parasite survived for a
      substantial period of time. Finally, the common concentrations of ethanol used
      for the disinfection of surfaces in household and/or laboratory, are sufficient
      for the inactivation of A. alata mesocercariae.

PMID- 24880240
TI  - Citalopram protects against cold-restraint stress-induced activation of brain
      derived neurotrophic factor and expression of nuclear factor kappa-light-chain
      enhancer of activated B cells in rats.
AB  - The present study evaluates the protective effect of citalopram against cold
      restraint stress (CRS) paradigm. Rats were pretreated with citalopram (0.1, 1.0,
      and 10.0 mg/kg) acutely and repeatedly for 21 days before exposure to the CRS
      procedure. None of the doses of citalopram attenuated CRS-induced gastric ulcers
      in the acute study. In contrast, repeated pretreatment of citalopram at a dose
      level of 0.1 mg/kg attenuated the CRS-induced gastric ulcers. Citalopram (0.1
      mg/kg) diminished CRS-induced increase in plasma corticosterone, but not plasma
      norepinephrine level in the chronic study indicating its effect on hypothalamic
      pituitary-adrenal axis function. Repeated citalopram (0.1 mg/kg) pretreatment
      attenuated CRS-induced changes in serotonin turnover in the hippocampus and
      amygdala. Moreover, repeated pretreatment with citalopram (0.1 mg/kg) mitigated
      the CRS-induced increase in the expression of brain-derived neurotrophic factor
      (BDNF) and nuclear factor kappa-light-chain-enhancer of activated B cells
      (NFkappaB) in the hippocampus and amygdala. These results suggest that there is a
      region- and a dose-specific effect of citalopram on CRS-induced BDNF-NFkappaB
      activation. Therefore, citalopram showed antistress activity in the CRS model
      through changes in the stress-responsive pathways such as hypothalamic-pituitary
      adrenal-axis and brain serotonergic system apart from decreasing the expression
      of BDNF and NFkappaB.

PMID- 24880242
TI  - Dynamic metabolism modelling of urban water services--demonstrating effectiveness
      as a decision-support tool for Oslo, Norway.
AB  - Urban water services are challenged from many perspectives and different
      stakeholders demand performance improvements along economic, social and
      environmental dimensions of sustainability. In response, urban water utilities
      systematically give more attention to criteria such as water safety, climate
      change adaptation and mitigation, environmental life cycle assessment (LCA),
      total cost efficiency, and on how to improve their operations within the water
      energy-carbon nexus. The authors of this paper collaborated in the development of
      a 'Dynamic Metabolism Model' (DMM). The model is developed for generic use in the
      sustainability assessment of urban water services, and it has been initially
      tested for the city of Oslo, Norway. The purpose has been to adopt a holistic
      systemic perspective to the analysis of metabolism and environmental impacts of
      resource flows in urban water and wastewater systems, in order to offer a tool
      for the examination of future strategies and intervention options in such
      systems. This paper describes the model and its application to the city of Oslo
      for the analysis time period 2013-2040. The external factors impacting decision
      making and interventions are introduced along with realistic scenarios developed
      for the testing, after consultation with officials at the Oslo Water and
      Wastewater Works (Norway). Possible interventions that the utility intends to set
      in motion are defined and numerically interpreted for incorporation into the
      model, and changes in the indicator values over the time period are determined.
      This paper aims to demonstrate the effectiveness and usefulness of the DMM, as a
      decision-support tool for water-wastewater utilities. The scenarios considered
      and interventions identified do not include all possible scenarios and
      interventions that can be relevant for water-wastewater utilities. 

PMID- 24880241
TI  - Bcl-2/Bax expression levels tend to influence AMPAergic trafficking mechanisms
      during hibernation in Mesocricetus auratus.
AB  - Hypothermia is a physiological condition assuring brain protection against
      hypoxic-related damages. In this context, investigations carried out on the
      facultative hibernator Mesocricetus auratus proved to be very useful for
      establishing the type of neurosignaling role exerted by cerebral alpha-amino-3
      hydroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPAR) subtypes during
      hypoxic/reperfusion injuries of the entrance (EN), torpor (TORP), and arousal
      (AROU) hibernating states. From the evaluation of the major AMPARs (GluR1 and
      GluR2), together with their scaffold proteins synapse-associated protein 97 kDa
      (SAP97) and PICK1, it resulted that GluR1 and SAP97 were mostly upregulated
      during the hypotensive (EN and TORP) states of the brainstem, amygdala, and
      hypothalamus, sites which are implicated with cardiovascular, motor, and sleep
      wake events. In addition, elevated expression densities of the pro-apoptotic
      factor Bcl-2-associated X protein (Bax) resulted to be correlated to marked amino
      cupric-silver stain signals during both hibernating states. Conversely, an
      increase of the neuroprotective factor GluR2, together with PICK1 and the anti
      apoptotic B cell lymphoma 2 (Bcl-2), appeared to be linked with reduced
      argyrophilic signals in most of the above areas of the hypertensive AROU state.
      These first indications highlight distinct protective/degenerative measures of
      the above factors constituting key on/off switches during the various hibernating
      states that may provide potential therapeutic bearings on sleeping disorders. 

PMID- 24880243
TI  - Effect of temperature on short chain fatty acids (SCFAs) accumulation and
      microbiological transformation in sludge alkaline fermentation with Ca(OH)2
      adjustment.
AB  - The effects of temperatures (15-55  degrees C) on the alkaline fermentation of
      sewage sludge were investigated in semi-continuous stirred tank reactors (semi -
      CSTR) at the pH of 10. The highest soluble chemical oxygen demand (SCOD) yield
      was obtained at 55  degrees C (764.2 mg/(gVS L d)), while the highest short chain
      fatty acids (SCFAs) yield was observed at 35  degrees C (319.8 mg/(gVS L d)), 1.5
      times higher than SCFAs yield at 55  degrees C (209.5 mg/(gVS L d)). The
      proportion of the intercellular organic substances being transferred to the slime
      layer of sludge flocs increased from 29% at 15  degrees C to 54% at 55  degrees
      C. But only a small part of soluble organic substances in the slime layers was
      converted to SCFAs at 55  degrees C. The dewaterability of sludge was better at
      35  degrees C than that at 55  degrees C. Microbiological community analysis
      showed the acid-producing microorganisms at the medium temperatures (25  degrees
      C and 35  degrees C) were more diverse and abundant than those at the low (15 
      degrees C) and high temperatures (55  degrees C). Clodtridium and Bacillus in
      Firmicutes and Gamma proteobacterium in Proteobacteria were the dominant
      functional bacterial species for high SCFA accumulation.

PMID- 24880244
TI  - Phenolic carbon tailored for the removal of polar organic contaminants from
      water: a solution to the metaldehyde problem?
AB  - Current water treatment technologies are inefficient at treating water
      contaminated with metaldehyde, an 8-member cyclic tetramer of acetaldehyde widely
      used as a molluscicide in large-scale agriculture and in gardens, and which has
      been frequently observed to breach European regulatory limits in the UK due to
      its high solubility and frequent use. Here, we examine the controls on
      metaldehyde adsorption onto activated phenolic carbon, namely the influence of
      activation degree, pore size distribution, particle size, point of zero charge
      and surface functionalisation, by synthesising "tailored" carbons from phenolic
      resin. Metaldehyde adsorption has been found to be independent of specific
      surface area (SBET), which is highly unusual for an adsorption process, and is
      favoured in carbons with (a) high microporosity with narrow pore size
      distribution, (b) presence of mesopores which allow efficient diffusive
      transport, and (c) an absence of negatively charged functional groups. The
      maximum adsorption capacity of the phenolic resin-derived carbons, tested at an
      elevated (i.e. exceeding environmental levels) water concentration of 64 mg
      metaldehyde/L, was 76 mg metaldehyde/g carbon compared with 13 mg metaldehyde/g
      carbon in industrial granular activated carbon (GAC). The phenolic resin-derived
      carbons and GAC showed similar adsorption kinetics with maximum metaldehyde
      uptake occurring within 30 min under batch adsorption conditions, although
      adsorption isotherms indicate much stronger adsorption of metaldehyde on the
      phenolic resin-derived carbons. Adsorption efficiency for metaldehyde was
      maintained even in the presence of high background concentrations of organic
      matter and inorganic salts, indicating the potential utility of these "designer"
      carbons in waste and/or drinking water treatment.

PMID- 24880245
TI  - How forest marsupials are affected by habitat degradation and fragmentation? A
      meta-analysis.
AB  - Habitat fragmentation and degradation are important biodiversity change drivers
      worldwide. Their effects have been described for many animal groups, but little
      is known about marsupials. We conducted a meta-analysis aiming to evaluate the
      actual effects of habitat fragmentation and degradation on forest marsupials.
      From a literature survey, we obtained 85 case studies reporting disturbance
      comparisons. We found a negative overall effect, as well as a negative effect for
      habitat fragmentation, but not for habitat degradation. Marsupials from Oceania
      were negatively affected by habitat disturbance, whereas there was no effect for
      those from South America. Arboreal marsupials were negatively affected, whereas
      terrestrial marsupials did not. Species from the families Dasyuridae (Antechinus
      spp.) and Microbiotheriidae (Dromiciops gliroides) showed to be sensitive to
      habitat disturbance. 

PMID- 24880246
TI  - The biocontrol agent Bacillus sp. CHEP5 primes the defense response against
      Cercospora sojina.
AB  - Glycine max (soybean) production can be dramatically affected by frogeye leaf
      spot (FLS) caused by Cercospora sojina Hara. The inoculation of biocontrol agents
      may be an alternative strategy for C. sojina control. The native biocontrol
      bacterium Bacillus sp. CHEP5 reduced the severity of FLS in soybean by inducing
      systemic resistance. We suggest that the defense response was primed since the
      expression of the defense related gene GmAOS was enhanced in induced plants
      treated with both methyl jasmonate and C. sojina. Furthermore, as GmAOS is
      related to jasmonic acid biosynthesis, we assume that this phytohormone is
      involved in induced systemic resistance signaling defense pathway in soybean
      against C. sojina. 

PMID- 24880248
TI  - Hemophagocytic lymphohistiocytosis secondary to Falciparum malaria in a 5 year
      old boy.

PMID- 24880247
TI  - Sulfone derivatives reduce growth, adhesion and aspartic protease SAP2 gene
      expression.
AB  - Fungal virulence factors represent a strategy for the design of new compounds
      with effective activities against Candida spp. Dichloromethyl-4-chloro-3
      nitrophenylsulfone (named Compound 1) and chlorodibromomethyl-4-hydrazino-3
      nitrophenylsulfone (Compound 2) versus Candida albicans virulence factors (SAP2
      expression and adhesion to Caco-2 cell line) were investigated. Candida albicans
      SC5314 and its mutants: Deltasap9, Deltasap10, Deltasap9/10 were used. MICs of
      the Compounds (concentrated at 0.0313-16 ug/ml) were determined using M27-A3.
      Percentage of cell inhibition was assessed spectrophotometrically (OD405) after
      48 h at 35  degrees C. The SAP2 expression was analyzed with the use of RT-PCR;
      relative quantification was normalized against ACT1 in cells grown in YEPD and on
      Caco-2. Adherence assay of C. albicans to Caco-2 was performed in a 24-well
      plate. Compound 1 showed higher activity (% = 100 at 4 ug/ml) than Compound 2
      (MIC90 = 16 ug/ml). Dichloromethyl at the para position of the phenyl ring
      exerted anti-Candidal potential. Under Compound 1, SAP2 was down-regulated in all
      the strains (P <= 0.05). Conversely, SAP2 was over-expressed in Deltasap9-10
      (untreated cells) compared with the wild-type. The Compounds significantly
      affected adherence to epithelium (P <= 0.05). The tested sulfones interfered with
      the adhesion of C. albicans cells to the epithelial tissues without affecting
      their viability after 90-min of incubation. The Compounds' mode of action was
      attributed to the reduced adhesiveness and the lower SAP2 expression. Saps9-10
      play a role in C. albicans adhesion and they can be involved in the sulfone
      resistance mechanisms.

PMID- 24880249
TI  - Intracellular aspartic proteinase Apr1p of Candida albicans is required for
      morphological transition under nitrogen-limited conditions but not for macrophage
      killing.
AB  - Vacuolar hydrolases have been thoroughly characterized in Saccharomyces
      cerevisiae, but their homologues in the fungal pathogen Candida albicans have
      received less attention. The genes APR1 and CPY1 of C. albicans encode putative
      vacuolar aspartic proteinase and serine carboxypeptidase, respectively. We
      examined properties of apr1Delta and cpy1Delta mutants, showing that Cpy1p
      molecular species detected in cell lysates of apr1Delta and its parental strain
      did not differ in molar mass. Processing of Cpy1p precursor is apparently
      independent of Apr1p. This is in contrast to S. cerevisiae, where vacuolar
      aspartic proteinase Pep4p is known to participate in the activation of other
      vacuolar hydrolases including serine carboxypeptidase. We also found that both
      apr1Delta and cpy1Delta strains are able to form hyphae in nutrient-rich
      filamentation media. However, proline as a sole nitrogen source induced
      filamentation only in cpy1Delta and its parental strain, but not in apr1Delta.
      This indicates the importance of Apr1p for the morphological transition under
      nitrogen-limited conditions. Despite that, the ability of apr1Delta to kill
      murine macrophages was not reduced under the conditions tested. 

PMID- 24880250
TI  - Cohabitation--relationships of corynebacteria and staphylococci on human skin.
AB  - Skin microbiome main cultivable aerobes in human are coagulase-negative
      staphylococci and lipophilic corynebacteria. Staphylococcus strains (155)
      belonging to 10 species and 105 strains of Corynebacterium belonging to nine
      species from the skin swabs of healthy male volunteers were investigated to
      determine their enzymatic activity to main metabolic substrates: carbohydrates,
      proteins, lipids, and response to factors present on the skin such as osmotic
      pressure, pH, and organic acids. The results showed that lipophilic
      corynebacteria have different capacity for adaptation on the skin than
      staphylococci. Most of Corynebacterium spp. expressed lack of proteinase,
      phospholipase, and saccharolytic enzymes activity. Corynebacteria were also more
      sensitive than Staphylococcus spp. to antimicrobial agents existing on human
      skin, especially to low pH. These characters can explain domination of
      Staphylococcus genera on healthy human skin. It can be suggested that within
      these two bacterial genus, there exists conceivable cooperation and reciprocal
      protection which results in their quantitative ratio. Such behavior must be
      considered as crucial for the stability of the population on healthy skin. 

PMID- 24880252
TI  - Shared decision making among parents of children with mental health conditions
      compared to children with chronic physical conditions.
AB  - High quality care in pediatrics involves shared decision making (SDM) between
      families and providers. The extent to which children with common mental health
      disorders experience SDM is not well known. The objectives of this study were to
      examine how parent-reported SDM varies by child health (physical illness, mental
      health condition, and comorbid mental and physical conditions) and to examine
      whether medical home care attenuates any differences. We analyzed data on
      children (2-17 years) collected through the 2009/2010 National Survey of Children
      with Special Health Care Needs. The sample consisted of parents of children in
      one of three child health categories: (1) children with a chronic physical
      illness but no mental health condition; (2) children with a common mental health
      condition but no chronic physical condition; and (3) children with comorbid
      mental and chronic physical conditions. The primary dependent variable was parent
      report of provider SDM. The primary independent variable was health condition
      category. Multivariate linear regression analyses were conducted. Multivariate
      analyses controlling for sociodemographic variables and parent-reported health
      condition impact indicated lower SDM among children with a common mental health
      condition-only (B = -0.40; p < 0.01) and children with comorbid conditions (B = 
      0.67; p < 0.01) compared to children with a physical condition-only. Differences
      in SDM for children with a common mental health condition-only were no longer
      significant in the model adjusting for medical home care. However, differences in
      SDM for children with comorbid conditions persisted after adjusting for medical
      home care. Increasing medical home care may help mitigate differences in SDM for
      children with mental health conditions-only. Other interventions may be needed to
      improve SDM among children with comorbid mental and physical conditions.

PMID- 24880251
TI  - Receiving versus being denied an abortion and subsequent tobacco use.
AB  - The negative health consequences of tobacco use are well documented. Some
      research finds women receiving abortions are at increased risk of subsequent
      tobacco use. This literature has methodological problems, most importantly,
      inappropriate comparison groups. This study uses data from the Turnaway Study, a
      longitudinal study of women who all sought, but did not all receive, abortions at
      30 facilities across the United States. Participants included women presenting
      just before an abortion facility's gestational age limit who received abortions
      (Near Limit Abortion Group, n = 452), just after the gestational limit who were
      denied abortions (Turnaways, n = 231), and who received first trimester abortions
      (First Trimester Abortion Group, n = 273). This study examined the association
      between receiving versus being denied an abortion and subsequent tobacco use over
      2-years. Trajectories of tobacco use over 2 years were compared using
      multivariate mixed effects regression. Women receiving abortion maintained their
      level of tobacco use over 2 years. Women denied abortion initially had lower
      levels of tobacco use than women receiving abortion, but increased their tobacco
      use from 1 week through 12-18 months post-abortion seeking and then decreased
      their use by 2 years post-abortion seeking. Baseline parity modified these
      associations. Receiving an abortion was not associated with an increase in
      tobacco use over time. Overall, women who carry unwanted pregnancies to term
      appear to demonstrate similar cessation and resumption patterns to other pregnant
      women.

PMID- 24880253
TI  - The Validity and Reliability of the Parent Fever Management Scale: A Study from
      Palestine.
AB  - Parental concern about childhood fever and consequent use of antipyretics is
      increasing. Little is known about childhood fever management among Arab parents.
      No scales to measure parents' fever management practices in Palestine are
      available. The aim of this study was to validate the Arabic version of the Parent
      Fever Management Scale (PFMS) using a sample of parents in Palestine. A standard
      "forward-backward" procedure was used to translate PFMS into Arabic language. It
      was then validated on a convenience sample of 402 parents between July and
      October 2012. Descriptive statistics were used, and instrument reliability was
      assessed for internal consistency using Cronbach's alpha coefficient. Validity
      was confirmed using convergent and known group validation. Applying the
      recommended scoring method, the median (interquartile range) score of the PFMS
      was 26 (23-30). Acceptable internal consistency was found (Cronbach's alpha =
      0.733) and the test-retest reliability value was 0.92 (P < 0.001). The Chi
      squared (chi (2)) test showed a significant relationship between PFMS groups and
      frequent daily administration of antipyretic groups (chi (2) = 52.86; P < 0.001).
      The PFMS sensitivity and specificity were 77.67 and 57.75 %, respectively. The
      positive and negative predictive values were 67.89 and 32.11 %, respectively. The
      Arabic version of the PFMS is a reliable and valid measure and can be used as a
      useful tool for health professionals to identify parents' fever management
      practices. The Arabic version of the PFMS can be used to reduce unnecessary
      parental practices in fever management for a febrile child.

PMID- 24880254
TI  - Hereditary angioedema: imaging manifestations and clinical management.
AB  - Hereditary angioedema is a genetic disorder typically related to insufficient or
      dysfunctional C1-esterase inhibitor. Patients present with episodic swelling of
      various body parts, such as the face, neck, bowel, genitals, and extremities.
      Acute or severe symptoms can lead to patients presenting to the emergency room,
      particularly when the neck and abdominopelvic regions are affected, which is
      often accompanied by radiologic imaging evaluation. Patients with hereditary
      angioedema can pose a diagnostic challenge for emergency department physicians
      and radiologists at initial presentation, and the correct diagnosis may be missed
      or delayed, due to lack of clinical awareness of the disease or lack of its
      consideration in the radiologic differential diagnosis. Timely diagnosis of
      hereditary angioedema and rapid initiation of appropriate therapy can avoid
      potentially life-threatening complications. This article focuses on the spectrum
      of common and characteristic acute imaging manifestations of hereditary
      angioedema and provides an update on important recent developments in its
      clinical management and treatment.

PMID- 24880255
TI  - Plain abdominal radiography in acute abdominal pain--is it really necessary?
AB  - The aims of this study are to audit the ordering of abdominal radiographs (AXR)
      in the emergency department (ED) and evaluate the current practices, knowledge
      and attitudes of emergency physicians with regard to ordering AXRs in patients
      presenting with acute abdominal pain. A retrospective study was undertaken at an
      ED of a tertiary hospital in Tasmania using clinical notes on patient presenting
      with acute abdominal pain who underwent an AXR. The study also included a short
      questionnaire, which assessed emergency physicians' knowledge of current imaging
      guidelines and clinical practice when ordering an AXR. During the study period,
      108 patients satisfied the selection criteria, and the AXR was reported as normal
      in 76 % (n = 82; p value <0.05), non-specific in 12 % (n = 13; p value <0.05) and
      abnormal in 12 % (n = 13; p value <0.05) of patients. Of those patients, 25 % (n
      = 27) of the AXRs did not meet indications listed in the Diagnostic Imaging
      Pathways published by the Western Australia Department of Health and were found
      not to benefit patient care. Of the 19 doctors who completed the survey, only 16
      % (n = 3) were aware of any clinical guidelines for imaging in this setting.
      Current guidelines should be followed when ordering imaging for patients with
      acute abdominal pain to minimise unnecessary patient radiation exposure, avoid
      delays in diagnosis and definitive patient management, reduce costs and therefore
      increase efficiency in ED. 

PMID- 24880256
TI  - Responses of proteolytic enzymes in embryonic axes of germinating bean seeds
      under copper stress.
AB  - The changes in protease activities in embryonic axes during the first days of
      bean (Phaseolus vulgaris L.) seed germination were investigated in response to
      copper stress. Synthetic substrates and specific protease inhibitors have been
      used to define qualitatively and quantitatively different catalytic classes,
      particularly endoproteases (EP), carboxypeptidases (CP) and aminopeptidases (AP),
      then identify which ones were affected in the presence of copper. In fact, a
      failure in storage proteins mobilization and a disorder of nitrogen supply at
      enzymatic level occurred in Cu. In fact, Cu inhibited azocaseinolytic activity
      (ACA) and cysteine-, aspartic-, serine-, and metallo-endopeptidases activities
      (Cys-EP, Asp-EP, Ser-Ep, and Met-EP, respectively). Besides, Cu affected leucine-
      and proline-aminopeptidases (LAP and PAP, respectively) and glycine
      carboxypeptidases (Gly-CP). The proteolytic responses might also be associated
      with the decrease in defense capacity in the Cu-treated embryos. 

PMID- 24880257
TI  - Effects of aflatoxin B1 exposure and sodium selenite supplementation on the
      histology, cell proliferation, and cell cycle of jejunum in broilers.
AB  - The aim of this study was to investigate the effects of aflatoxin B1 (AFB1)
      exposure and sodium selenite supplementation on the histology, cell proliferation
      and cell cycle of jejunum in broilers. A total of 240 1-day-old male AA broilers
      were divided into four groups of 60 each, fed with basal diet (control group),
      0.3 mg/kg AFB1 (AFB1 group), 0.4 mg/kg supplement Se (Se group), and 0.3 mg/kg
      AFB1 + 0.4 mg/kg supplement Se (AFB1 + Se group) for 21 days, respectively.
      Compared with the control group, decreased jejunal villus height, villus
      height/crypt ratio, and proliferation cell nuclear antigen (PCNA)-positive cells,
      and G2/M phase arrest and shedded epithelial cells on the tip of jejunal villus
      were observed in AFB1 groups at 7 and 14 days of age. However, the villus/crypt
      ratio, PCNA-positive cells and cell percentage of G0/G1, S, and G2/M phases had
      no significant differences between AFB1 group and control group at 21 days.
      Simultaneous supplementation with sodium selenite restored these parameters to be
      close to those in control group. In conclusion, 0.3 mg/kg AFB1 in the diet
      inhibits the development of broiler's jejunum by reducing cellular proliferation
      and inducing G2/M arrest during only the first 2 weeks after hatching.
      Supplementation of dietary sodium selenite at the concentration of 0.4 mg/kg Se
      had protective action against these toxic effects of AFB1.

PMID- 24880258
TI  - Communication: system-size scaling of Boltzmann and alternate Gibbs entropies.
AB  - It has recurrently been proposed that the Boltzmann textbook definition of
      entropy S(E) = k ln Omega(E) in terms of the number of microstates Omega(E) with
      energy E should be replaced by the expression S(G)(E) = k ln Sigma(E' <
      E)Omega(E') examined by Gibbs. Here, we show that SG either is equivalent to S in
      the macroscopic limit or becomes independent of the energy exponentially fast as
      the system size increases. The resulting exponential scaling makes the realistic
      use of SG unfeasible and leads in general to temperatures that are inconsistent
      with the notions of hot and cold.

PMID- 24880259
TI  - Communication: oscillating charge migration between lone pairs persists without
      significant interaction with nuclear motion in the glycine and Gly-Gly-NH-CH3
      radical cations.
AB  - Coupled electron-nuclear dynamics has been studied, using the Ehrenfest method,
      for four conformations of the glycine molecule and a single conformation of Gly
      Gly-NH-CH3. The initial electronic wavepacket was a superposition of eigenstates
      corresponding to ionization from the sigma lone pairs associated with the
      carbonyl oxygens and the amine nitrogen. For glycine, oscillating charge
      migration (when the nuclei were frozen) was observed for the 4 conformers studied
      with periods ranging from 2 to 5 fs, depending on the energy gap between the lone
      pair cationic states. When coupled nuclear motion was allowed (which was mainly
      NH2 partial inversion), the oscillations hardly changed. For Gly-Gly-NH-CH3,
      charge migration between the carbonyl oxygens and the NH2 lone pair can be
      observed with a period similar to glycine itself, also without interaction with
      nuclear motion. These simulations suggest that charge migration between lone
      pairs can occur independently of the nuclear motion. 

PMID- 24880260
TI  - Analytic energy gradient for the projected Hartree-Fock method.
AB  - We derive and implement the analytic energy gradient for the symmetry Projected
      Hartree-Fock (PHF) method avoiding the solution of coupled-perturbed HF-like
      equations, as in the regular unprojected method. Our formalism therefore has mean
      field computational scaling and cost, despite the elaborate multi-reference
      character of the PHF wave function. As benchmark examples, we here apply our
      gradient implementation to the ortho-, meta-, and para-benzyne biradicals, and
      discuss their equilibrium geometries and vibrational frequencies. 

PMID- 24880261
TI  - Estimating the entropy and quantifying the impurity of a swarm of surface-hopping
      trajectories: a new perspective on decoherence.
AB  - In this article, we consider the intrinsic entropy of Tully's fewest switches
      surface hopping (FSSH) algorithm (as estimated by the impurity of the density
      matrix) [J. Chem. Phys. 93, 1061 (1990)]. We show that, even for a closed system,
      the total impurity of a FSSH calculation increases in time (rather than stays
      constant). This apparent failure of the FSSH algorithm can be traced back to an
      incorrect, approximate treatment of the electronic coherence between wavepackets
      moving along different potential energy surfaces. This incorrect treatment of
      electronic coherence also prevents the FSSH algorithm from correctly describing
      wavepacket recoherences (which is a well established limitation of the FSSH
      method). Nevertheless, despite these limitations, the FSSH algorithm often
      predicts accurate observables because the electronic coherence density is
      modulated by a phase factor which varies rapidly in phase space and which often
      integrates to almost zero. Adding "decoherence" events on top of a FSSH
      calculation completely destroys the incorrect FSSH electronic coherence and
      effectively sets the Poincare recurrence time for wavepacket recoherence to
      infinity; this modification usually increases FSSH accuracy (assuming there are
      no recoherences) while also offering long-time stability for trajectories. In
      practice, we show that introducing "decoherence" events does not change the total
      FSSH impurity significantly, but does lead to more accurate evaluations of the
      impurity of the electronic subsystem. 

PMID- 24880262
TI  - Distinguishability and chiral stability in solution: effects of decoherence and
      intermolecular interactions.
AB  - We examine the effect of decoherence and intermolecular interactions (chiral
      discrimination energies) on the chiral stability and the distinguishability of
      initially pure versus mixed states in an open chiral system. Under a two-level
      approximation for a system, intermolecular interactions are introduced by a mean
      field theory, and interaction between a system and an environment is modeled by a
      continuous measurement of a population difference between the two chiral states.
      The resultant equations are explored for various parameters, with emphasis on the
      combined effects of the initial condition of the system, the chiral
      discrimination energies, and the decoherence in determining: the
      distinguishability as measured by a population difference between the initially
      pure and mixed states, and the decoherence process; the chiral stability as
      measured by the purity decay; and the stationary state of the system at times
      long relative to the time scales of the system dynamics and of the environmental
      effects. 

PMID- 24880263
TI  - Covalent bonds are created by the drive of electron waves to lower their kinetic
      energy through expansion.
AB  - An analysis based on the variation principle shows that in the molecules H2 (+),
      H2, B2, C2, N2, O2, F2, covalent bonding is driven by the attenuation of the
      kinetic energy that results from the delocalization of the electronic wave
      function. For molecular geometries around the equilibrium distance, two features
      of the wave function contribute to this delocalization: (i) Superposition of
      atomic orbitals extends the electronic wave function from one atom to two or more
      atoms; (ii) intra-atomic contraction of the atomic orbitals further increases the
      inter-atomic delocalization. The inter-atomic kinetic energy lowering that
      (perhaps counter-intuitively) is a consequence of the intra-atomic contractions
      drives these contractions (which per se would increase the energy). Since the
      contractions necessarily encompass both, the intra-atomic kinetic and potential
      energy changes (which add to a positive total), the fact that the intra-atomic
      potential energy change renders the total potential binding energy negative does
      not alter the fact that it is the kinetic delocalization energy that drives the
      bond formation. 

PMID- 24880264
TI  - Resonant activation in a colored multiplicative thermal noise driven closed
      system.
AB  - In this paper, we have demonstrated that resonant activation (RA) is possible
      even in a thermodynamically closed system where the particle experiences a random
      force and a spatio-temporal frictional coefficient from the thermal bath. For
      this stochastic process, we have observed a hallmark of RA phenomena in terms of
      a turnover behavior of the barrier-crossing rate as a function of noise
      correlation time at a fixed noise variance. Variance can be fixed either by
      changing temperature or damping strength as a function of noise correlation time.
      Our another observation is that the barrier crossing rate passes through a
      maximum with increase in coupling strength of the multiplicative noise. If the
      damping strength is appreciably large, then the maximum may disappear. Finally,
      we compare simulation results with the analytical calculation. It shows that
      there is a good agreement between analytical and numerical results. 

PMID- 24880265
TI  - Classical mapping for Hubbard operators: application to the double-Anderson
      model.
AB  - A classical Cartesian mapping for Hubbard operators is developed to describe the
      nonequilibrium transport of an open quantum system with many electrons. The
      mapping of the Hubbard operators representing the many-body Hamiltonian is
      derived by using analogies from classical mappings of boson creation and
      annihilation operators vis-a-vis a coherent state representation. The approach
      provides qualitative results for a double quantum dot array (double Anderson
      impurity model) coupled to fermionic leads for a range of bias voltages, Coulomb
      couplings, and hopping terms. While the width and height of the conduction peaks
      show deviations from the master equation approach considered to be accurate in
      the limit of weak system-leads couplings and high temperatures, the Hubbard
      mapping captures all transport channels involving transition between many
      electron states, some of which are not captured by approximate nonequilibrium
      Green function closures. 

PMID- 24880266
TI  - Generating accurate dipole moment surfaces using modified Shepard interpolation.
AB  - We outline an approach for building molecular dipole moment surfaces using
      modified Shepard interpolation. Our approach is highly automated, requires
      minimal parameterization, and is iteratively improvable. Using the water molecule
      as a test case, we investigate how different aspects of the interpolation scheme
      affect the rate of convergence of calculated IR spectral line intensities. It is
      found that the interpolation scheme is sensitive to coordinate singularities
      present at linear geometries. Due to the generally monotonic nature of the dipole
      moment surface, the one-part weight function is found to be more effective than
      the more complicated two-part variant, with first-order interpolation also giving
      better-than-expected results. Almost all sensible schemes for choosing
      interpolation reference data points are found to exhibit acceptable convergence
      behavior. 

PMID- 24880268
TI  - Phase separation in solutions with specific and nonspecific interactions.
AB  - Protein solutions, which tend to be thermodynamically stable under physiological
      conditions, can demix into protein-enriched and protein-depleted phases when
      stressed. Using a lattice-gas model of proteins with both isotropic and specific,
      directional interactions, we calculate the critical conditions for phase
      separation for model proteins with up to four patches via Monte Carlo simulations
      and statistical associating fluid theory. Given a fixed specific interaction
      strength, the critical value of the isotropic energy, which accounts for
      dispersion forces and nonspecific interactions, measures the stability of the
      solution with respect to nonspecific interactions. Phase separation is suppressed
      by the formation of protein complexes, which effectively passivate the strongly
      associating sites on the monomers. Nevertheless, we find that protein models with
      three or more patches can form extended aggregates that phase separate despite
      the assembly of passivated complexes, even in the absence of nonspecific
      interactions. We present a unified view of the critical behavior of model fluids
      with anisotropic interactions, and we discuss the implications of these results
      for the thermodynamic stability of protein solutions. 

PMID- 24880267
TI  - Modeling delay in genetic networks: from delay birth-death processes to delay
      stochastic differential equations.
AB  - Delay is an important and ubiquitous aspect of many biochemical processes. For
      example, delay plays a central role in the dynamics of genetic regulatory
      networks as it stems from the sequential assembly of first mRNA and then protein.
      Genetic regulatory networks are therefore frequently modeled as stochastic birth
      death processes with delay. Here, we examine the relationship between delay birth
      death processes and their appropriate approximating delay chemical Langevin
      equations. We prove a quantitative bound on the error between the pathwise
      realizations of these two processes. Our results hold for both fixed delay and
      distributed delay. Simulations demonstrate that the delay chemical Langevin
      approximation is accurate even at moderate system sizes. It captures dynamical
      features such as the oscillatory behavior in negative feedback circuits, cross
      correlations between nodes in a network, and spatial and temporal information in
      two commonly studied motifs of metastability in biochemical systems. Overall,
      these results provide a foundation for using delay stochastic differential
      equations to approximate the dynamics of birth-death processes with delay. 

PMID- 24880269
TI  - Daubechies wavelets for linear scaling density functional theory.
AB  - We demonstrate that Daubechies wavelets can be used to construct a minimal set of
      optimized localized adaptively contracted basis functions in which the Kohn-Sham
      orbitals can be represented with an arbitrarily high, controllable precision.
      Ground state energies and the forces acting on the ions can be calculated in this
      basis with the same accuracy as if they were calculated directly in a Daubechies
      wavelets basis, provided that the amplitude of these adaptively contracted basis
      functions is sufficiently small on the surface of the localization region, which
      is guaranteed by the optimization procedure described in this work. This approach
      reduces the computational costs of density functional theory calculations, and
      can be combined with sparse matrix algebra to obtain linear scaling with respect
      to the number of electrons in the system. Calculations on systems of 10,000 atoms
      or more thus become feasible in a systematic basis set with moderate
      computational resources. Further computational savings can be achieved by
      exploiting the similarity of the adaptively contracted basis functions for
      closely related environments, e.g., in geometry optimizations or combined
      calculations of neutral and charged systems.

PMID- 24880271
TI  - Calculation of exact vibrational spectra for P2O and CH2NH using a phase space
      wavelet basis.
AB  - ''Exact" quantum dynamics calculations of vibrational spectra are performed for
      two molecular systems of widely varying dimensionality (P2O and CH2NH), using a
      momentum-symmetrized Gaussian basis. This basis has been previously shown to
      defeat exponential scaling of computational cost with system dimensionality. The
      calculations were performed using the new "SwitchBLADE" black-box code, which
      utilizes both dimensionally independent algorithms and massive parallelization to
      compute very large numbers of eigenstates for any fourth-order force field
      potential, in a single calculation. For both molecules considered here, many
      thousands of vibrationally excited states were computed, to at least an
      "intermediate" level of accuracy (tens of wavenumbers). Future modifications to
      increase the accuracy to "spectroscopic" levels, along with other potential
      future improvements of the new code, are also discussed. 

PMID- 24880270
TI  - Nonorthogonal molecular orbital method: single-determinant theory.
AB  - Using the variational principle, we have derived a variant of the Adams-Gilbert
      equation for nonorthogonal orbitals of a single-determinant wave function, which
      we name the modified Adams-Gilbert equation. If we divide the molecular system
      into several subsystems, such as bonds, lone pairs, and residues, we can solve
      the equations for the subsystems one by one. Thus, this procedure has linear
      scaling. We have presented a practical procedure for solving the equations that
      is also applicable to macromolecular calculations. The numerical examples show
      that the procedure yields, with reasonable effort, results comparable with those
      of the Hartree-Fock-Roothaan method for orthogonal orbitals. To resolve the
      convergence difficulty in the self-consistent-field iterations, we have found
      that virtual molecular-orbital shifts are very effective. 

PMID- 24880272
TI  - When a single hole aligns several spins: double exchange in organic systems.
AB  - The double exchange is a well-known and technically important phenomenon in solid
      state physics. Ionizing a system composed of two antiferromagnetically coupled
      high-spin units, the ground state of which is a singlet state, may actually
      produce a high-spin ground state. This work illustrates the possible occurrence
      of such a phenomenon in organic chemistry. The here-considered high-spin units
      are triangulenes, the ground state of which is a triplet. Bridging two of them
      through a benzene ring produces a molecular architecture of singlet ground state.
      A careful exploitation of a series of unrestricted density functional
      calculations enables one to avoid spin contamination in the treatment of the
      doublet states and shows that under ionization the system becomes of quartet
      multiplicity in its ground state. The possibility to align more than three spins
      from conjugated hydrocarbon polyradicals is explored, considering partially
      hydrogenated triangulenes. A dramatic example shows that ionization of a singlet
      ground state molecule may generate a decuplet. 

PMID- 24880273
TI  - Model free isoconversional procedure for evaluating the effective activation
      energy values of thermally stimulated processes in dinitroimidazoles.
AB  - The decomposition kinetics of 1,4-dinitroimidazole, 2,4-dinitroimidazole, and N
      methyl-2,4-dinitroimidazole have been investigated using thermogravimetry
      differential thermal analysis technique under N2 atmosphere at the flow rate 100
      cm(3)/min. The Flynn-Wall-Ozawa method and the Friedman method were used for the
      estimation of the effective activation energy values. These model free
      isoconversional kinetic methods showed variation in the calculated values due to
      the approximation of temperature integral used in the derivations of the kinetic
      equations. The model compounds were decomposed by multi-step kinetics evident
      from the nonlinear relationship of the effective activation energy values with
      the conversion rate. Three different reaction pathways namely NO2 elimination, NO
      elimination, and HONO elimination are expected to play crucial role in the
      decomposition of nitroimidazoles. The model dinitroimidazoles represent different
      decomposition kinetics, and the reaction pathways the NO2 elimination, and NO
      elimination compete with each other for the decomposition mechanism. The present
      study is certainly helpful in understanding the decomposition kinetics, and
      dynamics of substituted nitroimidazoles to be used for fuel, and explosive
      applications. 

PMID- 24880274
TI  - Excited state dynamics in SO2. I. Bound state relaxation studied by time-resolved
      photoelectron-photoion coincidence spectroscopy.
AB  - The excited state dynamics of isolated sulfur dioxide molecules have been
      investigated using the time-resolved photoelectron spectroscopy and time-resolved
      photoelectron-photoion coincidence techniques. Excited state wavepackets were
      prepared in the spectroscopically complex, electronically mixed
      (B)(1)B1/(A)(1)A2, Clements manifold following broadband excitation at a range of
      photon energies between 4.03 eV and 4.28 eV (308 nm and 290 nm, respectively).
      The resulting wavepacket dynamics were monitored using a multiphoton ionisation
      probe. The extensive literature associated with the Clements bands has been
      summarised and a detailed time domain description of the ultrafast relaxation
      pathways occurring from the optically bright (B)(1)B1 diabatic state is
      presented. Signatures of the oscillatory motion on the (B)(1)B1/(A)(1)A2 lower
      adiabatic surface responsible for the Clements band structure were observed. The
      recorded spectra also indicate that a component of the excited state wavepacket
      undergoes intersystem crossing from the Clements manifold to the underlying
      triplet states on a sub-picosecond time scale. Photoelectron signal growth time
      constants have been predominantly associated with intersystem crossing to the
      (c)(3)B2 state and were measured to vary between 750 and 150 fs over the
      implemented pump photon energy range. Additionally, pump beam intensity studies
      were performed. These experiments highlighted parallel relaxation processes that
      occurred at the one- and two-pump-photon levels of excitation on similar time
      scales, obscuring the Clements band dynamics when high pump beam intensities were
      implemented. Hence, the Clements band dynamics may be difficult to disentangle
      from higher order processes when ultrashort laser pulses and less-differential
      probe techniques are implemented.

PMID- 24880275
TI  - Non-adiabatic and intersystem crossing dynamics in SO2. II. The role of triplet
      states in the bound state dynamics studied by surface-hopping simulations.
AB  - The importance of triplet states in the photorelaxation dynamics of SO2 is
      studied by mixed quantum-classical dynamics simulations. Using the SHARC method,
      standing for Surface Hopping including ARbitrary Couplings, intersystem crossing
      (ISC) processes caused by spin-orbit coupling are found occurring on an ultrafast
      time scale (few 100 fs) and thus competing with internal conversion. While in the
      singlet-only dynamics only oscillatory population transfer between the (1)B1 and
      (1)A2 states is observed, in the dynamics including singlet and triplet states we
      find additionally continuous ISC to the (3)B2 state and to a smaller extent to
      the (3)B1/(3)A2 coupled states. The populations obtained from the dynamics are
      discussed with respect to the overall nuclear motion and in the light of recent
      TRPEPICO studies [I. Wilkinson, A. E. Boguslavskiy, J. Mikosch, D. M. Villeneuve,
      H.-J. Worner, M. Spanner, S. Patchkovskii, and A. Stolow, "Excited state dynamics
      in SO2. I. Bound state relaxation studied by time-resolved photoelectron-photoion
      coincidence spectroscopy," J. Chem. Phys. 140, 204301 (2014)]. 

PMID- 24880276
TI  - Excited state dynamics in SO2. III. An ab initio quantum study of single- and
      multi-photon ionization.
AB  - We present an ab initio quantum study of the photoelectron spectra of sulfur
      dioxide, based on wavepacket propagations on manifolds of ionic, and
      excited/Rydberg states. We obtain excellent agreement for two different cases.
      First, the one photon ionization case where we can reproduce all details of the
      experimental spectrum and demonstrate the influence of the conical intersection
      between two of the ionic states. Then the multiphoton ionization regime, in which
      the dynamics of the wave packet on the two lowest singlet states is directly
      mapped in the spectra via a pump-probe scheme, as proposed in the experimental
      companion paper [I. Wilkinson et al., J. Chem. Phys. 140, 204301 (2014)]. 

PMID- 24880277
TI  - Dynamical photoionization observables of the CS molecule: the role of electron
      correlation.
AB  - Highly correlated calculations are performed on the primary ionic states and the
      prominent satellite present in the outer valence photoelectron spectrum of carbon
      monosulfide (CS). Dyson orbitals are coupled to accurate one particle continuum
      orbitals to provide a correlated description of energy dependent cross sections,
      asymmetry parameters, branching ratios, and molecular frame photoelectron angular
      distributions. The comparison with results obtained at the Hartree-Fock and
      Density Functional Theory level shows the strong sensitivity of these observables
      to details of the correlation in the bound states. The behaviour of the well
      characterized satellite state is analyzed in detail, and shows differences from
      the relevant primary states, revealing the limitations of a simple intensity
      borrowing mechanism. The results resolve the intensity disagreement with
      experiment obtained at the level of the sudden approximation. 

PMID- 24880278
TI  - Interchannel coupling effects in the valence photoionization of SF6.
AB  - The complex Kohn and polyatomic Schwinger variational techniques have been
      employed to illustrate the interchannel coupling correlation effects in the
      valence photoionization dynamics of SF6. Partial photoionization cross sections
      and asymmetry parameters of six valence subshells (1t1g, 5t1u, 1t2u, 3eg, 1t2g,
      4t1u) are discussed in the framework of several theoretical and experimental
      studies. The complex Kohn results are in rather good agreement with experimental
      results, indicative of the fact that the interchannel coupling effects alter the
      photoionization dynamics significantly. We find that the dominant effect of
      interchannel coupling is to reduce the magnitude of shape resonant cross sections
      near the threshold and to induce resonant features in other channels to which
      resonances are coupled. The long-standing issue concerning ordering of the
      valence orbitals is addressed and confirmed 4t1u (6)1t2g (6)3eg (4)(5t1u (6)+1t2u
      (6)) 1t1g (6) as the most likely ordering. 

PMID- 24880279
TI  - Rovibrational levels and wavefunctions of Cl(-)H2O.
AB  - In this paper, we report vibrational levels computed for Cl(-)H2O and compare
      with experimental observations and previous approximate calculations. In
      addition, we present rovibrational levels. The calculations are done using a
      symmetry adapted Lanczos algorithm and a product basis set and include all six
      vibrational coordinates. The basis functions have amplitude in both wells and
      enable us to determine tunnelling splittings. We use the potential energy surface
      of Rheinecker and Bowman [J. Chem. Phys. 125, 133206 (2006)]. Rovibrational
      levels are assigned vibrational labels using vibrational parent analysis. Our
      results reveal the effect of previous approximations, but are in fairly good
      agreement with prior calculations and experiments. 

PMID- 24880280
TI  - Multiple ionization and hydrogen loss from neutral and positively-charged
      coronene.
AB  - In this work, we present a density functional theory study of the structure and
      stability of neutral and positively-charged coronene C24H12(q+). In particular,
      we have investigated (i) adiabatic and vertical ionization potentials up to
      charge q = 9, (ii) the corresponding infrared spectra, and (iii) dissociation
      energies and potential energy surfaces for several hydrogen loss channels:
      sequential H+H, H+H(+), H(+)+H, H(+)+H(+), and direct H2 and H2(+). We have found
      that the stability of positively-charged coronene is extremely high as a
      consequence of the molecule's capability to redistribute the charge all over the
      structure. The computed dissociation energies and fragmentation barriers show
      that there is competition between different hydrogen loss channels and that the
      relative importance of these channels depends on the charge of the molecule. From
      a careful analysis of the potential energy surface we conclude that the channel
      with the lowest barrier corresponds to the loss of H2 from neutral, singly-,
      doubly-, and triply-charged coronene, H2(+) from quadruply-charged coronene and
      H(+)+H(+) from quintuply-charged coronene.

PMID- 24880281
TI  - Rotational spectrum of tryptophan.
AB  - The rotational spectrum of the natural amino acid tryptophan has been observed
      for the first time using a combination of laser ablation, molecular beams, and
      Fourier transform microwave spectroscopy. Independent analysis of the rotational
      spectra of individual conformers has conducted to a definitive identification of
      two different conformers of tryptophan, with one of the observed conformers never
      reported before. The analysis of the (14)N nuclear quadrupole coupling constants
      is of particular significance since it allows discrimination between structures,
      thus providing structural information on the orientation of the amino group. Both
      observed conformers are stabilized by an O-H...N hydrogen bond in the side chain
      and a N-H...pi interaction forming a chain that reinforce the strength of
      hydrogen bonds through cooperative effects. 

PMID- 24880282
TI  - The effect of structural changes on charge transfer states in a light-harvesting
      carotenoid-diaryl-porphyrin-C60 molecular triad.
AB  - We present a detailed study of charge transfer (CT) excited states for a large
      number of configurations in a light-harvesting Carotenoid-diaryl-Porphyrin-C60
      (CPC60) molecular triad. The chain-like molecular triad undergoes photoinduced
      charge transfer process exhibiting a large excited state dipole moment, making it
      suitable for application to molecular-scale opto-electronic devices. An important
      consideration is that the structural flexibility of the CPC60 triad impacts its
      dynamics in solvents. Since experimentally measured dipole moments for the triad
      of ~110 D and ~160 D strongly indicate a range in structural variability in the
      excited state, studying the effect of structural changes on the CT excited state
      energetics furthers the understanding of its charge transfer states. We have
      calculated the variation in the lowest CT excited state energies by performing a
      scan of possible variation in the structure of the triad. Some of these
      configurations were generated by incrementally scanning a 360 degrees  torsional
      (dihedral) twist at the C60-porhyrin linkage and the porphyrin-carotenoid
      linkage. Additionally, five different CPC60 conformations were studied to
      determine the effect of pi-conjugation and particle-hole Coulombic attraction on
      the CT excitation energies. Our calculations show that configurational changes in
      the triad induces a variation of ~0.6 eV in CT excited state energies in the gas
      phase. The corresponding calculated excited state dipoles show a range of 47 D
      188 D. The absorption spectra and density of states of these structures show
      little variation except for the structures where the porphyrin and aryl
      conjugation is changed. 

PMID- 24880283
TI  - Systematics of small parahydrogen clusters in two dimensions.
AB  - We studied by means of computer simulations the low temperature properties of two
      dimensional parahydrogen clusters comprising between N = 7 and 30 molecules.
      Computed energetics is in quantitative agreement with that reported in the only
      previous study [M. C. Gordillo and D. M. Ceperley, Phys. Rev. B 65, 174527
      (2002)], but a generally stronger superfluid response is obtained here for
      clusters with more than ten molecules. Moreover, all the clusters, including the
      smallest one, display a well-defined, clearly identifiable solidlike structure;
      with only one possible exception, those with fewer than N = 25 molecules are
      (almost) entirely superfluid at the lowest temperature considered here (i.e., T =
      0.25 K), and can thus be regarded as nanoscale "supersolids." The implications of
      these results on a possible bulk two-dimensional superfluid phase of parahydrogen
      are discussed. 

PMID- 24880285
TI  - Dynamics of the time-resolved stimulated Raman scattering spectrum in presence of
      transient vibronic inversion of population on the example of optically excited
      trans-beta-apo-8'-carotenal.
AB  - We have studied the effect of transient vibrational inversion of population in
      trans-beta-apo-8(')-carotenal on the time-resolved femtosecond stimulated Raman
      scattering (TR-FSRS) signal. The experimental data are interpreted by applying a
      quantum mechanical approach, using the formalism of projection operators for
      constructing the theoretical model of TR-FSRS. Within this theoretical frame we
      explain the presence of transient Raman losses on the Stokes side of the TR-FSRS
      spectrum as the effect of vibrational inversion of population. In view of the
      obtained experimental and theoretical results, we conclude that the excited S2
      electronic level of trans-beta-apo-8(')-carotenal relaxes towards the S0 ground
      state through a set of four vibrational sublevels of S1 state. 

PMID- 24880284
TI  - Time-, frequency-, and wavevector-resolved x-ray diffraction from single
      molecules.
AB  - Using a quantum electrodynamic framework, we calculate the off-resonant
      scattering of a broadband X-ray pulse from a sample initially prepared in an
      arbitrary superposition of electronic states. The signal consists of single
      particle (incoherent) and two-particle (coherent) contributions that carry
      different particle form factors that involve different material transitions.
      Single-molecule experiments involving incoherent scattering are more influenced
      by inelastic processes compared to bulk measurements. The conditions under which
      the technique directly measures charge densities (and can be considered as
      diffraction) as opposed to correlation functions of the charge-density are
      specified. The results are illustrated with time- and wavevector-resolved signals
      from a single amino acid molecule (cysteine) following an impulsive excitation by
      a stimulated X-ray Raman process resonant with the sulfur K-edge. Our theory and
      simulations can guide future experimental studies on the structures of nano
      particles and proteins. 

PMID- 24880287
TI  - A theoretical and experimental study of pressure broadening of the oxygen A-band
      by helium.
AB  - The rotationally resolved magnetic dipole absorption spectrum of the oxygen A
      band b(1)Sigma(g)(+)(v=0) <- X(3)Sigma(g)(-)(v=0) perturbed by collisions with
      helium was studied theoretically using the impact approximation. To calculate the
      relaxation matrix, scattering calculations were performed on a newly computed
      helium-oxygen (b(1)Sigma(g)(+)) interaction potential as well as on a helium
      oxygen (X(3)Sigma(g)(-)) interaction potential from the literature. The
      calculated integrated line cross sections and broadening coefficients are in good
      agreement with experimental results from the literature. Additionally, cavity
      ring-down experiments were performed in the wings of the spectral lines for a
      quantitative study of line-mixing, i.e., the redistribution of rotational line
      intensities by helium-oxygen collisions. It is shown that inclusion of line
      mixing in the theory is required to reproduce the experimentally determined
      absolute absorption strengths as a function of the density of the helium gas.

PMID- 24880286
TI  - Multiphoton ionization of large water clusters.
AB  - Water clusters are multimers of water molecules held together by hydrogen bonds.
      In the present work, multiphoton ionization in the UV range coupled with time of
      flight mass spectrometry has been applied to water clusters with up to 160
      molecules in order to obtain information on the electronic states of clusters of
      different sizes up to dimensions that can approximate the bulk phase. The
      dependence of ion intensities of water clusters and their metastable fragments
      produced by laser ionization at 355 nm on laser power density indicates a (3+1)
      photon resonance-enhanced multiphoton ionization process. It also explains the
      large increase of ionization efficiency at 355 nm compared to that at 266 nm.
      Indeed, it was found, by applying both nanosecond and picosecond laser ionization
      with the two different UV wavelengths, that no water cluster sequences after n =
      9 could be observed at 266 nm, whereas water clusters up to m/z 2000 Th in
      reflectron mode and m/z 3000 Th in linear mode were detected at 355 nm. The
      agreement between our findings on clusters of water, especially true in the range
      with n > 10, and reported data for liquid water supports the hypothesis that
      clusters above a critical dimension can approximate the liquid phase. It should
      thus be possible to study clusters just above 10 water molecules, for getting
      information on the bulk phase structure. 

PMID- 24880288
TI  - The vibrational spectrum of FeO2(+) isomers--theoretical benchmark and
      experiment.
AB  - Infrared photodissociation is used to record the vibrational spectrum of FeO2
      (+)(He)2-4 which shows three bands at 1035, 980, and 506 cm(-1). Quantum chemical
      multi-reference configuration interaction calculations (MRCISD) of structures and
      harmonic frequencies show that these bands are due to two different isomers, an
      inserted dioxo complex with Fe in the +V oxidation state and a side-on superoxo
      complex with Fe in the +II oxidation state. These two are separated by a
      substantial barrier, 53 kJ/mol, whereas the third isomer, an end-on complex
      between Fe(+) and an O2 molecule, is easily converted into the side-on complex.
      For all three isomers, states of different spin multiplicity have been
      considered. Our best energies are computed at the MRCISD+Q level, including
      corrections for complete active space and basis set extension, core-valence
      correlation, relativistic effects, and zero-point vibrational energy. The average
      coupled pair functional (ACPF) yields very similar energies. Density functional
      theory (DFT) differs significantly from our best estimates for this system, with
      the TPSS functional yielding the best results. The other functionals tested are
      BP86, PBE, B3LYP, TPSSh, and B2PLYP. Complete active space second order
      perturbation theory (CASPT2) performs better than DFT, but less good than ACPF. 

PMID- 24880289
TI  - Reaction mechanisms and kinetics of the iminovinylidene radical with NO: ab
      initio study.
AB  - The nitric oxide (NO) is a notorious compound for polluting environment. Recent
      year, removing nitric oxide from the atmosphere becomes a focus of the
      investigation. In our work, we study the iminovinylidene (HNCC) radical reacted
      with NO molecule. The mechanism and kinetic for reaction of the HNCC radical with
      the NO molecule is investigated via considering the possible channels of the N
      and O atoms of NO attacking the N and C atoms of the HNCC based on the high level
      ab initio molecular orbital calculations in conjunction with variational TST and
      RRKM calculations. The species involved have been optimized at the B3LYP/6
      311++G(3df,2p) level and their single-point energies are refined by the
      CCSD(T)/aug-cc-PVQZ//B3LYP/6-311++G(3df,2p) method. The calculated potential
      energy surfaces indicated that energetically the most favorable channel for the
      HNCC + NO reaction was predicted to be the formation of HNC+CNO (P8) product via
      the addition reaction of the C atom of HNCC radical and the N atom of NO with the
      head to head orientation. To rationalize the scenario of the calculated results,
      we also employ the Fukui functions and HSAB theory to seek for a possible
      explanation. In addition, the reaction rate constants were calculated using
      VariFlex code, and the results show that the total rate coefficient, ktotal, at
      Ar pressure 760 Torr can be represented with an equation: ktotal = 6.433 * 10(
      11) T (0.100) exp(0.275 kcal mol(-1)/RT) at T = 298-3000 K, in units of cm(3)
      molecule(-1) s(-1). 

PMID- 24880290
TI  - Hydration dynamics in water clusters via quantum molecular dynamics simulations.
AB  - We have investigated the hydration dynamics in size selected water clusters with
      n = 66, 104, 200, 500, and 1000 water molecules using molecular dynamics
      simulations. To study the most fundamental aspects of relaxation phenomena in
      clusters, we choose one of the simplest, still realistic, quantum mechanically
      treated test solute, an excess electron. The project focuses on the time
      evolution of the clusters following two processes, electron attachment to neutral
      equilibrated water clusters and electron detachment from an equilibrated water
      cluster anion. The relaxation dynamics is significantly different in the two
      processes, most notably restoring the equilibrium final state is less effective
      after electron attachment. Nevertheless, in both scenarios only minor cluster
      size dependence is observed. Significantly different relaxation patterns
      characterize electron detachment for interior and surface state clusters,
      interior state clusters relaxing significantly faster. This observation may
      indicate a potential way to distinguish surface state and interior state water
      cluster anion isomers experimentally. A comparison of equilibrium and non
      equilibrium trajectories suggests that linear response theory breaks down for
      electron attachment at 200 K, but the results converge to reasonable agreement at
      higher temperatures. Relaxation following electron detachment clearly belongs to
      the linear regime. Cluster relaxation was also investigated using two different
      computational models, one preferring cavity type interior states for the excess
      electron in bulk water, while the other simulating non-cavity structure. While
      the cavity model predicts appearance of several different hydrated electron
      isomers in agreement with experiment, the non-cavity model locates only cluster
      anions with interior excess electron distribution. The present simulations show
      that surface isomers computed with the cavity predicting potential show similar
      dynamical behavior to the interior clusters of the non-cavity type model.
      Relaxation associated with cavity collapse presents, however, unique dynamical
      signatures. 

PMID- 24880291
TI  - Differential and integral cross sections for the rotationally inelastic
      scattering of methyl radicals with H2 and D2.
AB  - Comparisons are presented of experimental and theoretical studies of the
      rotationally inelastic scattering of CD3 radicals with H2 and D2 collision
      partners at respective collision energies of 680 +/- 75 and 640 +/- 60 cm(-1).
      Close-coupling quantum-mechanical calculations performed using a newly
      constructed ab initio potential energy surface (PES) provide initial-to-final CD3
      rotational level (n, k -> n', k') integral and differential cross sections (ICSs
      and DCSs). The DCSs are compared with crossed molecular beam and velocity map
      imaging measurements of angular scattering distributions, which serve as a
      critical test of the accuracy of the new PES. In general, there is very good
      agreement between the experimental measurements and the calculations. The DCSs
      for CD3 scattering from both H2 and D2 peak in the forward hemisphere for n' = 2
      4 and shift more to sideways and backward scattering for n' = 5. For n' = 6-8,
      the DCSs are dominated by backward scattering. DCSs for a particular CD3 n -> n'
      transition have a similar angular dependence with either D2 or H2 as collision
      partner. Any differences between DCSs or ICSs can be attributed to mass effects
      because the PES is unchanged for CD3-H2 and CD3-D2 collisions. Further
      comparisons are drawn between the CD3-D2 scattering and results for CD3-He
      presented in our recent paper [O. Tkac, A. G. Sage, S. J. Greaves, A. J. Orr
      Ewing, P. J. Dagdigian, Q. Ma, and M. H. Alexander, Chem. Sci. 4, 4199 (2013)].
      These systems have the same reduced mass, but are governed by different PESs. 

PMID- 24880292
TI  - Hypervalence in monoxides and dioxides of superalkali clusters.
AB  - F2Li3, a superalkali cluster, is characterized as having a lower adiabatic
      ionization energy than its elemental alkali counterpart and, coupled with the
      presence of complex molecular orbitals, suggests promise for novel bonding
      possibilities. CBS-QB3 composite method was used to study three distinct cluster
      isomers, as well as their cationic (+1) and anionic (-1) species, to identify
      energetic trends and observe geometric changes. Oxides were then generated from
      these clusters, of which three distinct monoxides and nine dioxides were obtained
      upon structure optimization. Identical calculations were performed for the oxide
      species and their charged counterparts. Some of the most stable oxides produced
      appear to possess hypervalent lithium and oxygen atoms, forming unique structures
      with exceptional stability. 

PMID- 24880293
TI  - Ionization satellites of the ArHe dimer.
AB  - Ionization satellites are key ingredients in the control of post ionization
      processes such as molecular dissociation and interatomic Coulombic decay. Here,
      using the high-level ab initio method of multi-reference configuration
      interaction up to triple excitations, we study the potential energy curves (PECs)
      of the ionization satellites of the ArHe dimer. With this model system, we
      demonstrate that the simple model used in alkaline earth metal and rare gas
      complexes to describe the satellites as a Rydberg electron moving on top of a
      dicationic core does not fully hold for the rare gas clusters. The more complex
      valence structure in the rare gas atom leads to the mixing of different
      electronic configurations of the dimer. This prevents one from assigning a single
      dicationic parent state to some of the ionization satellites. We further analyze
      the structure of the different PECs, demonstrating how the density of the Rydberg
      electron is reflected in the structure of the PEC wherever the simple model is
      applicable. 

PMID- 24880294
TI  - Breakdown of ionic character of molecular alkali bromides in inner-valence
      photoionization.
AB  - The inner-valence region of alkali bromide XBr (X=Li, Na, K, Rb) vapours has been
      studied experimentally by means of synchrotron radiation excited photoelectron
      spectroscopy. Experimental spectra were analyzed by comparing them with available
      theoretical results and previous experiments. Ionic character of alkali bromides
      is seen to change in the inner-valence region with increasing atomic number of
      the alkali atom. A mechanism involving mixing between Br 4s and Rb 4p orbitals
      has been suggested to account for the fine structure observed in inner-valence
      ionization region of RbBr. 

PMID- 24880296
TI  - Phase diagram of two-dimensional hard ellipses.
AB  - We report the phase diagram of two-dimensional hard ellipses as obtained from
      replica exchange Monte Carlo simulations. The replica exchange is implemented by
      expanding the isobaric ensemble in pressure. The phase diagram shows four
      regions: isotropic, nematic, plastic, and solid (letting aside the hexatic phase
      at the isotropic-plastic two-step transition [E. P. Bernard and W. Krauth, Phys.
      Rev. Lett. 107, 155704 (2011)]). At low anisotropies, the isotropic fluid turns
      into a plastic phase which in turn yields a solid for increasing pressure (area
      fraction). Intermediate anisotropies lead to a single first order transition
      (isotropic-solid). Finally, large anisotropies yield an isotropic-nematic
      transition at low pressures and a high-pressure nematic-solid transition. We
      obtain continuous isotropic-nematic transitions. For the transitions involving
      quasi-long-range positional ordering, i.e., isotropic-plastic, isotropic-solid,
      and nematic-solid, we observe bimodal probability density functions. This
      supports first order transition scenarios. 

PMID- 24880295
TI  - Quantum mechanical force field for hydrogen fluoride with explicit electronic
      polarization.
AB  - The explicit polarization (X-Pol) theory is a fragment-based quantum chemical
      method that explicitly models the internal electronic polarization and
      intermolecular interactions of a chemical system. X-Pol theory provides a
      framework to construct a quantum mechanical force field, which we have extended
      to liquid hydrogen fluoride (HF) in this work. The parameterization, called XPHF,
      is built upon the same formalism introduced for the XP3P model of liquid water,
      which is based on the polarized molecular orbital (PMO) semiempirical quantum
      chemistry method and the dipole-preserving polarization consistent point charge
      model. We introduce a fluorine parameter set for PMO, and find good agreement for
      various gas-phase results of small HF clusters compared to experiments and ab
      initio calculations at the M06-2X/MG3S level of theory. In addition, the XPHF
      model shows reasonable agreement with experiments for a variety of structural and
      thermodynamic properties in the liquid state, including radial distribution
      functions, interaction energies, diffusion coefficients, and densities at various
      state points. 

PMID- 24880297
TI  - Interaction of a long alkyl chain protic ionic liquid and water.
AB  - A combined experimental/theoretical approach has been used to investigate the
      role of water in modifying the microscopic interactions characterizing the
      optical response of 1-butyl-ammonium nitrate (BAN) water solutions. Raman
      spectra, dominated by the signal from the protic ionic liquid, were collected as
      a function of the water content, and the corresponding spatial organization of
      the ionic couples, as well as their local arrangement with water molecules, was
      studied exploiting classical molecular dynamics calculations. High quality
      spectroscopic data, combined with a careful analysis, revealed that water affects
      the vibrational spectrum BAN in solution: as the water concentration is
      increased, peaks assigned to stretching modes show a frequency hardening together
      with a shape narrowing, whereas the opposite behavior is observed for peaks
      assigned to bending modes. Calculation results clearly show a nanometric spatial
      organization of the ionic couples that is not destroyed on increasing the water
      content at least within an intermediate range. Our combined results show indeed
      that small water concentrations even increase the local order. Water molecules
      are located among ionic couples and are closer to the anion than the cation, as
      confirmed by the computation of the number of H-bonds which is greater for water
      anion than for water-cation. The whole results set thus clarifies the microscopic
      scenario of the BAN-water interaction and underlines the main role of the
      extended hydrogen bond network among water molecules and nitrate anions. 

PMID- 24880298
TI  - Molecular modeling of vapor-deposited polymer glasses.
AB  - We have investigated the properties of vapor-deposited glasses prepared from
      short polymer chains using molecular dynamics simulations. Vapor-deposited
      polymer glasses are found to have higher density and higher kinetic stability
      than ordinary glasses prepared by gradual cooling of the corresponding
      equilibrium liquid. In contrast to results for binary Lennard-Jones glasses, the
      deposition rate is found to play an important role in the stability of polymer
      vapor-deposited glasses. Glasses deposited at the slowest deposition rate and at
      the optimal substrate temperature are found to correspond to the ordinary glasses
      that one could hypothetically prepare by cooling the liquid at rates that are 4-5
      orders of magnitude slower than those accessible in the current simulations. For
      intermediate-length polymer chains, the resulting vapor-deposited glasses are
      found to be highly anisotropic. For short chains, however, the glasses are
      isotropic, showing that structural anisotropy is not a necessary condition for
      formation of stable glasses by physical vapor deposition. 

PMID- 24880300
TI  - Molecular near-field antenna effect in resonance hyper-Raman scattering:
      intermolecular vibronic intensity borrowing of solvent from solute through dipole
      dipole and dipole-quadrupole interactions.
AB  - We quantitatively interpret the recently discovered intriguing phenomenon related
      to resonance Hyper-Raman (HR) scattering. In resonance HR spectra of all-trans
      beta-carotene (beta-carotene) in solution, vibrations of proximate solvent
      molecules are observed concomitantly with the solute beta-carotene HR bands. It
      has been shown that these solvent bands are subject to marked intensity
      enhancements by more than 5 orders of magnitude under the presence of beta
      carotene. We have called this phenomenon the molecular-near field effect.
      Resonance HR spectra of beta-carotene in benzene, deuterated benzene,
      cyclohexane, and deuterated cyclohexane have been measured precisely for a
      quantitative analysis of this effect. The assignments of the observed peaks are
      made by referring to the infrared, Raman, and HR spectra of neat solvents. It has
      been revealed that infrared active and some Raman active vibrations are active in
      the HR molecular near-field effect. The observed spectra in the form of
      difference spectra (between benzene/deuterated benzene and cyclohexane/deuterated
      cyclohexane) are quantitatively analyzed on the basis of the extended vibronic
      theory of resonance HR scattering. The theory incorporates the coupling of
      excited electronic states of beta-carotene with the vibrations of a proximate
      solvent molecule through solute-solvent dipole-dipole and dipole-quadrupole
      interactions. It is shown that the infrared active modes arise from the dipole
      dipole interaction, whereas Raman active modes from the dipole-quadrupole
      interaction. It is also shown that vibrations that give strongly polarized Raman
      bands are weak in the HR molecular near-field effect. The observed solvent HR
      spectra are simulated with the help of quantum chemical calculations for various
      orientations and distances of a solvent molecule with respect to the solute. The
      observed spectra are best simulated with random orientations of the solvent
      molecule at an intermolecular distance of 10 A. 

PMID- 24880299
TI  - On the collective network of ionic liquid/water mixtures. IV. Kinetic and
      rotational depolarization.
AB  - Dielectric spectroscopy is a measure of the collective Coulomb interaction in
      liquid systems. Adding ionic liquids to an aqueous solution results in a decrease
      of the static value of the generalized dielectric constant which cannot be
      attributed to kinetic depolarization models characterized by the static
      conductivity and rotational relaxation constant. However, a dipolar Poisson
      Boltzmann model computing the water depolarization in the proximity of ions is
      not only successful for simple electrolytes but also in case of molecular ionic
      liquids. Moreover, our simple geometric hydration model is also capable to
      explain the dielectric depolarization. Both models compute the dielectric
      constant of water and obtain the overall dielectric constant by averaging the
      values of its components, water and the ionic liquid, weighted by their volume
      occupancies. In this sense, aqueous ionic liquid mixtures seem to behave like
      polar mixtures. 

PMID- 24880301
TI  - Residual entropy of ices and clathrates from Monte Carlo simulation.
AB  - We calculated the residual entropy of ices (Ih, Ic, III, V, VI) and clathrates
      (I, II, H), assuming the same energy of all configurations satisfying the Bernal
      Fowler ice rules. The Metropolis Monte Carlo simulations in the range of
      temperatures from infinity to a size-dependent threshold were followed by the
      thermodynamic integration. Convergence of the simulation and the finite-size
      effects were analyzed using the quasichemical approximation and the Debye-Huckel
      theory applied to the Bjerrum defects. The leading finite-size error terms, ln
      N/N, 1/N, and for the two-dimensional square ice model also 1/N(3/2), were used
      for an extrapolation to the thermodynamic limit. Finally, we discuss the
      influence of unequal energies of proton configurations. 

PMID- 24880302
TI  - Collective vibrations of water-solvated hydroxide ions investigated with
      broadband 2DIR spectroscopy.
AB  - The infrared spectra of aqueous solutions of NaOH and other strong bases exhibit
      a broad continuum absorption for frequencies between 800 and 3500 cm(-1), which
      is attributed to the strong interactions of the OH(-) ion with its solvating
      water molecules. To provide molecular insight into the origin of the broad
      continuum absorption feature, we have performed ultrafast transient absorption
      and 2DIR experiments on aqueous NaOH by exciting the O-H stretch vibrations and
      probing the response from 1350 to 3800 cm(-1) using a newly developed sub-70 fs
      broadband mid-infrared source. These experiments, in conjunction with harmonic
      vibrational analysis of OH(-)(H2O)n (n = 17) clusters, reveal that O-H stretch
      vibrations of aqueous hydroxides arise from coupled vibrations of multiple water
      molecules solvating the ion. We classify the vibrations of the hydroxide complex
      by symmetry defined by the relative phase of vibrations of the O-H bonds hydrogen
      bonded to the ion. Although broad and overlapping spectral features are observed
      for 3- and 4-coordinate ion complexes, we find a resolvable splitting between
      asymmetric and symmetric stretch vibrations, and assign the 2850 cm(-1) peak
      infrared spectra of aqueous hydroxides to asymmetric stretch vibrations. 

PMID- 24880303
TI  - String model for the dynamics of glass-forming liquids.
AB  - We test the applicability of a living polymerization theory to describe
      cooperative string-like particle rearrangement clusters (strings) observed in
      simulations of a coarse-grained polymer melt. The theory quantitatively describes
      the interrelation between the average string length L, configurational entropy
      Sconf, and the order parameter for string assembly Phi without free parameters.
      Combining this theory with the Adam-Gibbs model allows us to predict the
      relaxation time tau in a lower temperature T range than accessible by current
      simulations. In particular, the combined theories suggest a return to Arrhenius
      behavior near Tg and a low T residual entropy, thus avoiding a Kauzmann "entropy
      crisis." 

PMID- 24880304
TI  - Ionic asymmetry and solvent excluded volume effects on spherical electric double
      layers: a density functional approach.
AB  - In this article, we present a classical density functional theory for electrical
      double layers of spherical macroions that extends the capabilities of
      conventional approaches by accounting for electrostatic ion correlations, size
      asymmetry, and excluded volume effects. The approach is based on a recent
      approximation introduced by Hansen-Goos and Roth for the hard sphere excess free
      energy of inhomogeneous fluids [J. Chem. Phys. 124, 154506 (2006); Hansen-Goos
      and Roth, J. Phys.: Condens. Matter 18, 8413 (2006)]. It accounts for the proper
      and efficient description of the effects of ionic asymmetry and solvent excluded
      volume, especially at high ion concentrations and size asymmetry ratios including
      those observed in experimental studies. Additionally, we utilize a leading
      functional Taylor expansion approximation of the ion density profiles. In
      addition, we use the mean spherical approximation for multi-component charged
      hard sphere fluids to account for the electrostatic ion correlation effects.
      These approximations are implemented in our theoretical formulation into a
      suitable decomposition of the excess free energy which plays a key role in
      capturing the complex interplay between charge correlations and excluded volume
      effects. We perform Monte Carlo simulations in various scenarios to validate the
      proposed approach, obtaining a good compromise between accuracy and computational
      cost. We use the proposed computational approach to study the effects of ion
      size, ion size asymmetry, and solvent excluded volume on the ion profiles,
      integrated charge, mean electrostatic potential, and ionic coordination number
      around spherical macroions in various electrolyte mixtures. Our results show that
      both solvent hard sphere diameter and density play a dominant role in the
      distribution of ions around spherical macroions, mainly for experimental water
      molarity and size values where the counterion distribution is characterized by a
      tight binding to the macroion, similar to that predicted by the Stern model. 

PMID- 24880306
TI  - Modeling charge transport in C60-based self-assembled monolayers for applications
      in field-effect transistors.
AB  - We have investigated the conductance properties of C60-containing self-assembled
      monolayers (SAMs), which are used in organic field-effect transistors, employing
      a combination of molecular-dynamics simulations, semiempirical electronic
      structure calculations, and Landauer transport theory. The results reveal the
      close relation between the transport characteristics and the structural and
      electronic properties of the SAM. Furthermore, both local pathways of charge
      transport in the SAMs and the influence of structural fluctuations are analyzed. 

PMID- 24880305
TI  - Intrinsic ferromagnetism in hexagonal boron nitride nanosheets.
AB  - Understanding the mechanism of ferromagnetism in hexagonal boron nitride
      nanosheets, which possess only s and p electrons in comparison with normal
      ferromagnets based on localized d or f electrons, is a current challenge. In this
      work, we report an experimental finding that the ferromagnetic coupling is an
      intrinsic property of hexagonal boron nitride nanosheets, which has never been
      reported before. Moreover, we further confirm it from ab initio calculations. We
      show that the measured ferromagnetism should be attributed to the localized pi
      states at edges, where the electron-electron interaction plays the role in this
      ferromagnetic ordering. More importantly, we demonstrate such edge-induced
      ferromagnetism causes a high Curie temperature well above room temperature. Our
      systematical work, including experimental measurements and theoretical
      confirmation, proves that such unusual room temperature ferromagnetism in
      hexagonal boron nitride nanosheets is edge-dependent, similar to widely reported
      graphene-based materials. It is believed that this work will open new
      perspectives for hexagonal boron nitride spintronic devices. 

PMID- 24880307
TI  - Melting transition of Lennard-Jones fluid in cylindrical pores.
AB  - Three-stage pseudo-supercritical transformation path and multiple-histogram
      reweighting technique are employed for the determination of solid-liquid
      coexistence of the Lennard-Jones (12-6) fluid, in a structureless cylindrical
      pore of radius, R, ranging from 4 to 20 molecular diameters. The Gibbs free
      energy difference is evaluated using thermodynamic integration method by
      connecting solid and liquid phases under confinement via one or more intermediate
      states without any first order phase transition among them. The thermodynamic
      melting temperature, Tm, is found to oscillate for pore size, R < 8, which is in
      agreement with the behavior observed for the melting temperature in slit pores.
      However, Tm for almost all pore sizes is less than the bulk case, which is
      contrary to the behavior seen for the slit pore. The oscillation in Tm decays at
      around pore radius R = 8, and beyond that shift in the melting temperature with
      respect to the bulk case is in line with the prediction of the Gibbs-Thomson
      equation. 

PMID- 24880308
TI  - Binding energy and mechanical stability of single- and multi-walled carbon
      nanotube serpentines.
AB  - Recently, Geblinger et al. [Nat. Nanotechnol. 3, 195 (2008)] and Machado et al.
      [Phys. Rev. Lett. 110, 105502 (2013)] reported the experimental and molecular
      dynamics realization of S-like shaped single-walled carbon nanotubes (CNTs), the
      so-called CNT serpentines. We reported here results from continuum modeling of
      the binding energy gamma between different single- and multi-walled CNT
      serpentines and substrates as well as the mechanical stability of the CNT
      serpentine formation. The critical length for the mechanical stability and
      adhesion of different CNT serpentines are determined in dependence of EiIi, d,
      and gamma, where EiIi and d are the CNT bending stiffness and distance of the CNT
      translation period. Our continuum model is validated by comparing its solution to
      full-atom molecular dynamics calculations. The derived analytical solutions are
      of great importance for understanding the interaction mechanism between different
      single- and multi-walled CNT serpentines and substrates. 

PMID- 24880309
TI  - Interaction of epitaxial silicene with overlayers formed by exposure to Al atoms
      and O2 molecules.
AB  - As silicene is not chemically inert, the study and exploitation of its electronic
      properties outside of ultrahigh vacuum environments require the use of insulating
      capping layers. In order to understand if aluminum oxide might be a suitable
      encapsulation material, we used high-resolution synchrotron photoelectron
      spectroscopy to study the interactions of Al atoms and O2 molecules, as well as
      the combination of both, with epitaxial silicene on thin ZrB2(0001) films grown
      on Si(111). The deposition of Al atoms onto silicene, up to the coverage of about
      0.4 Al per Si atoms, has little effect on the chemical state of the Si atoms. The
      silicene-terminated surface is also hardly affected by exposure to O2 gas, up to
      a dose of 4500 L. In contrast, when Al-covered silicene is exposed to the same
      dose, a large fraction of the Si atoms becomes oxidized. This is attributed to
      dissociative chemisorption of O2 molecules by Al atoms at the surface, producing
      reactive atomic oxygen species that cause the oxidation. It is concluded that
      aluminum oxide overlayers prepared in this fashion are not suitable for
      encapsulation since they do not prevent but actually enhance the degradation of
      silicene. 

PMID- 24880310
TI  - Density functional theory for carbon dioxide crystal.
AB  - We present a density functional approach to describe the solid-liquid phase
      transition, interfacial and crystal structure, and properties of polyatomic CO2.
      Unlike previous phase field crystal model or density functional theory, which are
      derived from the second order direct correlation function, the present density
      functional approach is based on the fundamental measure theory for hard-sphere
      repulsion in solid. More importantly, the contributions of enthalpic interactions
      due to the dispersive attractions and of entropic interactions arising from the
      molecular architecture are integrated in the density functional model. Using the
      theoretical model, the predicted liquid and solid densities of CO2 at equilibrium
      triple point are in good agreement with the experimental values. Based on the
      structure of crystal-liquid interfaces in different planes, the corresponding
      interfacial tensions are predicted. Their respective accuracies need to be
      tested. 

PMID- 24880311
TI  - Spin-dependent thermoelectronic transport of a single molecule magnet Mn(dmit)2.
AB  - We investigate spin-dependent thermoelectronic transport properties of a single
      molecule magnet Mn(dmit)2 sandwiched between two Au electrodes using first
      principles density functional theory combined with nonequilibrium Green's
      function method. By applying a temperature difference between the two Au
      electrodes, spin-up and spin-down currents flowing in opposite directions can be
      induced due to asymmetric distribution of the spin-up and spin-down transmission
      spectra around the Fermi level. A pure spin current and 100% spin polarization
      are achieved by tuning back-gate voltage to the system. The spin caloritronics of
      the molecule with a perpendicular conformation is also explored, where the spin
      down current is blocked strongly. These results suggest that Mn(dmit)2 is a
      promising material for spin caloritronic applications. 

PMID- 24880312
TI  - Atomic imaging and modeling of H2O2(g) surface passivation, functionalization,
      and atomic layer deposition nucleation on the Ge(100) surface.
AB  - Passivation, functionalization, and atomic layer deposition nucleation via
      H2O2(g) and trimethylaluminum (TMA) dosing was studied on the clean Ge(100)
      surface at the atomic level using scanning tunneling microscopy (STM) and
      scanning tunneling spectroscopy (STS). Chemical analysis of the surface was
      performed using x-ray photoelectron spectroscopy, while the bonding of the
      precursors to the substrate was modeled with density functional theory (DFT). At
      room temperature, a saturation dose of H2O2(g) produces a monolayer of a mixture
      of -OH or -O species bonded to the surface. STS confirms that H2O2(g) dosing
      eliminates half-filled dangling bonds on the clean Ge(100) surface. Saturation of
      the H2O2(g) dosed Ge(100) surface with TMA followed by a 200  degrees C anneal
      produces an ordered monolayer of thermally stable Ge-O-Al bonds. DFT models and
      STM simulations provide a consistent model of the bonding configuration of the
      H2O2(g) and TMA dosed surfaces. STS verifies the TMA/H2O2/Ge surface has an
      unpinned Fermi level with no states in the bandgap demonstrating the ability of a
      Ge-O-Al monolayer to serve as an ideal template for further high-k deposition. 

PMID- 24880313
TI  - Three-dimensional polymeric structures of single-wall carbon nanotubes.
AB  - We explore by ab initio calculations the possible crystalline phases of
      polymerized single-wall carbon nanotubes (P-SWNTs) and determine their
      structural, elastic, and electronic properties. Based on direct cross-linking and
      intertube sliding-assisted cross-linking mechanisms, we have identified a series
      of stable three-dimensional polymeric structures for the zigzag nanotubes up to
      (10,0). Among proposed P-SWNT phases, the structures with favorable diamond-like
      sp(3) intertube bonding configuration and small tube cross-section distortion are
      found to be the most energetically stable ones. These polymeric crystalline
      phases exhibit high bulk and shear moduli superior to SWNT bundles, and show
      metallic or semiconducting properties depending on the diameter of constituent
      tubes. We also propose by hydrostatic pressure simulations that the intertube
      sliding between van der Waals bonded nanotubes may be an effective route to
      promote the polymerization of SWNTs under pressure. 

PMID- 24880314
TI  - Electron-stimulated reactions in layered CO/H2O films: hydrogen atom diffusion
      and the sequential hydrogenation of CO to methanol.
AB  - Low-energy (100 eV) electron-stimulated reactions in layered H2O/CO/H2O ices are
      investigated. For CO layers buried in amorphous solid water (ASW) films at depths
      of 50 monolayers (ML) or less from the vacuum interface, both oxidation and
      reduction reactions are observed. However, for CO buried more deeply in ASW
      films, only the reduction of CO to methanol is observed. Experiments with layered
      films of H2O and D2O show that the hydrogen atoms participating in the reduction
      of the buried CO originate in the region that is 10-50 ML below the surface of
      the ASW films and subsequently diffuse through the film. For deeply buried CO
      layers, the CO reduction reactions quickly increase with temperature above ~60 K.
      We present a simple chemical kinetic model that treats the diffusion of hydrogen
      atoms in the ASW and sequential hydrogenation of the CO to methanol to account
      for the observations. 

PMID- 24880315
TI  - Alkyl chain length-dependent surface reaction of dodecahydro-N-alkylcarbazoles on
      Pt model catalysts.
AB  - The concept of liquid organic hydrogen carriers (LOHC) holds the potential for
      large scale chemical storage of hydrogen at ambient conditions. Herein, we
      compare the dehydrogenation and decomposition of three alkylated carbazole-based
      LOHCs, dodecahydro-N-ethylcarbazole (H12-NEC), dodecahydro-N-propylcarbazole (H12
      NPC), and dodecahydro-N-butylcarbazole (H12-NBC), on Pt(111) and on Al2O3
      supported Pt nanoparticles. We follow the thermal evolution of these systems
      quantitatively by in situ high-resolution X-ray photoelectron spectroscopy. We
      show that on Pt(111) the relevant reaction steps are not affected by the
      different alkyl substituents: for all LOHCs, stepwise dehydrogenation to NEC,
      NPC, and NBC is followed by cleavage of the C-N bond of the alkyl chain starting
      at 380-390 K. On Pt/Al2O3, we discern dealkylation on defect sites already at 350
      K, and on ordered, (111)-like facets at 390 K. The dealkylation process at the
      defects is most pronounced for NEC and least pronounced for NBC. 

PMID- 24880316
TI  - Physisorption of molecular hydrogen on carbon nanotube with vacant defects.
AB  - Physisorption of molecular hydrogen on single-walled carbon nanotubes (SWCNTs) is
      important for its engineering applications and hydrogen energy storage. Using
      molecular dynamics simulation, we study the physisorption of molecular hydrogen
      on a SWCNT with a vacant defect, focusing on the effect of the vacant defect size
      and external parameters such as temperature and pressure. We find that hydrogen
      can be physisorbed inside a SWCNT through a vacant defect when the defect size is
      above a threshold. By controlling the size of the defects, we are able to extract
      hydrogen molecules from a gas mixture and store them inside the SWCNT. We also
      find that external parameters, such as low temperature and high pressure, enhance
      the physisorption of hydrogen molecules inside the SWCNT. In addition, the
      storage efficiency can be improved by introducing more defects, i.e., reducing
      the number of carbon atoms on the SWCNT. 

PMID- 24880317
TI  - Effect of particle adsorption rates on the disproportionation process in
      pickering stabilised bubbles.
AB  - The degree of shrinkage of particle stabilised bubbles of various sizes, in a
      polydisperse bubble dispersion, has been investigated in the light of the finite
      adsorption times for the particles and the disproportionation kinetics of the
      bubbles. For the case where the system contains an abundance of particles we find
      a threshold radius, above which bubbles are stabilised without any significant
      reduction in their size. Bubbles with an initial radius below this threshold on
      the other hand undergo a large degree of shrinkage prior to stabilisation. As the
      ratio of the available particles to the bubbles is reduced, it is shown that the
      final bubble size, for the larger bubbles in the distribution, becomes
      increasingly governed by the number of particles, rather than their adsorption
      time per se. For systems with "adsorption controlled" shrinkage ratio, the final
      bubble distribution is found to be wider than the initial one, while for a
      "particle number controlled" case it is actually narrower. Starting from a
      unimodal bubble size distribution, we predict that at intermediate times, prior
      to the full stabilisation of all bubbles, the distribution breaks up into a
      bimodal one. However, the effect is transient and a unimodal final bubble size
      distribution is recovered, when all the bubbles are stabilised by the particles. 

PMID- 24880318
TI  - Massively parallel molecular dynamics simulation of formation of clathrate
      hydrate precursors at planar water-methane interfaces: insights into
      heterogeneous nucleation.
AB  - The formation of methane-hydrate precursors at large planar water-methane
      interfaces has been studied using massively parallel molecular dynamics in
      systems of varying size from around 10 000 to almost 7 * 10(6) molecules. This
      process took two distinct steps. First, the concentration of solvated methane
      clusters increases just inside the aqueous domain via slow diffusion from the
      methane-water interface, forming "clusters" of solvated methane molecules.
      Second, the re-ordering process of solvated methane and water molecules takes
      place in a manner very roughly consistent with the "blob" hypothesis, although
      with important differences, to form hydrate precursors, necessary for subsequent
      hydrate nucleation and crystallisation. It was found that larger system sizes
      serve to promote the formation rate of precursors. 

PMID- 24880320
TI  - Parameterization of a mesoscopic model for the self-assembly of linear sodium
      alkyl sulfates.
AB  - A systematic approach to develop mesoscopic models for a series of linear anionic
      surfactants (CH3(CH2)n - 1OSO3Na, n = 6, 9, 12, 15) by dissipative particle
      dynamics (DPD) simulations is presented in this work. The four surfactants are
      represented by coarse-grained models composed of the same head group and
      different numbers of identical tail beads. The transferability of the DPD model
      over different surfactant systems is carefully checked by adjusting the repulsive
      interaction parameters and the rigidity of surfactant molecules, in order to
      reproduce key equilibrium properties of the aqueous micellar solutions observed
      experimentally, including critical micelle concentration (CMC) and average
      micelle aggregation number (Nag). We find that the chain length is a good index
      to optimize the parameters and evaluate the transferability of the DPD model. Our
      models qualitatively reproduce the essential properties of these surfactant
      analogues with a set of best-fit parameters. It is observed that the logarithm of
      the CMC value decreases linearly with the surfactant chain length, in agreement
      with Klevens' rule. With the best-fit and transferable set of parameters, we have
      been able to calculate the free energy contribution to micelle formation per
      methylene unit of -1.7 kJ/mol, very close to the experimentally reported value. 

PMID- 24880319
TI  - Binding of solvated peptide (EPLQLKM) with a graphene sheet via simulated coarse
      grained approach.
AB  - Binding of a solvated peptide A1 ((1)E (2)P (3)L (4)Q (5)L (6)K (7)M) with a
      graphene sheet is studied by a coarse-grained computer simulation involving input
      from three independent simulated interaction potentials in hierarchy. A number of
      local and global physical quantities such as energy, mobility, and binding
      profiles and radius of gyration of peptides are examined as a function of
      temperature (T). Quantitative differences (e.g., the extent of binding within a
      temperature range) and qualitative similarities are observed in results from
      three simulated potentials. Differences in variations of both local and global
      physical quantities suggest a need for such analysis with multiple inputs in
      assessing the reliability of both quantitative and qualitative observations.
      While all three potentials indicate binding at low T and unbinding at high T, the
      extent of binding of peptide with the temperature differs. Unlike un-solvated
      peptides (with little variation in binding among residues), solvation accentuates
      the differences in residue binding. As a result the binding of solvated peptide
      at low temperatures is found to be anchored by three residues, (1)E, (4)Q, and
      (6)K (different from that with the un-solvated peptide). Binding to unbinding
      transition can be described by the variation of the transverse (with respect to
      graphene sheet) component of the radius of gyration of the peptide (a potential
      order parameter) as a function of temperature. 

PMID- 24880321
TI  - Microstructure of sheared monosized colloidal suspensions resulting from
      hydrodynamic and electrostatic interactions.
AB  - Hydrodynamic and near-particle interactions in sheared suspensions are
      communicated through suspension microstructure to produce a wide variety of
      rheological behaviors. To characterize this microstructure, the individual
      positions of monosized silica particles flowing through a microchannel are
      obtained with near simulation-level detail. The pair distribution functions of
      the microstructure at moderate to high Peclet number shear rates are very similar
      to previous numerical studies. Viscometric functions calculated based on the
      detailed microstructure obtained through this technique show qualitative
      agreement with computational results. These results elucidate the origins of
      shear-thickening of suspensions at high shear rates. While efforts are taken to
      screen electrostatic interactions to study hydrodynamic and Brownian
      interactions, the role of electrostatic interaction between particles is also
      investigated by reducing suspension ionic strength. These non-hydrodynamic
      electrostatic interactions result in a loss of anisotropy that generally agrees
      with previous findings of "soft" particle systems. 

PMID- 24880322
TI  - Collapse transitions in thermosensitive multi-block copolymers: a Monte Carlo
      study.
AB  - Monte Carlo simulations are performed on a simple cubic lattice to investigate
      the behavior of a single linear multiblock copolymer chain of various lengths N.
      The chain of type (AnBn)m consists of alternating A and B blocks, where A are
      solvophilic and B are solvophobic and N = 2nm. The conformations are classified
      in five cases of globule formation by the solvophobic blocks of the chain. The
      dependence of globule characteristics on the molecular weight and on the number
      of blocks, which participate in their formation, is examined. The focus is on
      relative high molecular weight blocks (i.e., N in the range of 500-5000 units)
      and very differing energetic conditions for the two blocks (very good-almost
      athermal solvent for A and bad solvent for B). A rich phase behavior is observed
      as a result of the alternating architecture of the multiblock copolymer chain. We
      trust that thermodynamic equilibrium has been reached for chains of N up to 2000
      units; however, for longer chains kinetic entrapments are observed. The
      comparison among equivalent globules consisting of different number of B-blocks
      shows that the more the solvophobic blocks constituting the globule the bigger
      its radius of gyration and the looser its structure. Comparisons between globules
      formed by the solvophobic blocks of the multiblock copolymer chain and their
      homopolymer analogs highlight the important role of the solvophilic A-blocks. 

PMID- 24880323
TI  - Precursory signatures of protein folding/unfolding: from time series correlation
      analysis to atomistic mechanisms.
AB  - Folded conformations of proteins in thermodynamically stable states have long
      lifetimes. Before it folds into a stable conformation, or after unfolding from a
      stable conformation, the protein will generally stray from one random
      conformation to another leading thus to rapid fluctuations. Brief structural
      changes therefore occur before folding and unfolding events. These short-lived
      movements are easily overlooked in studies of folding/unfolding for they
      represent momentary excursions of the protein to explore conformations in the
      neighborhood of the stable conformation. The present study looks for precursory
      signatures of protein folding/unfolding within these rapid fluctuations through a
      combination of three techniques: (1) ultrafast shape recognition, (2) time series
      segmentation, and (3) time series correlation analysis. The first procedure
      measures the differences between statistical distance distributions of atoms in
      different conformations by calculating shape similarity indices from molecular
      dynamics simulation trajectories. The second procedure is used to discover the
      times at which the protein makes transitions from one conformation to another.
      Finally, we employ the third technique to exploit spatial fingerprints of the
      stable conformations; this procedure is to map out the sequences of changes
      preceding the actual folding and unfolding events, since strongly correlated
      atoms in different conformations are different due to bond and steric
      constraints. The aforementioned high-frequency fluctuations are therefore
      characterized by distinct correlational and structural changes that are
      associated with rate-limiting precursors that translate into brief segments.
      Guided by these technical procedures, we choose a model system, a fragment of the
      protein transthyretin, for identifying in this system not only the precursory
      signatures of transitions associated with alpha helix and beta hairpin, but also
      the important role played by weaker correlations in such protein folding
      dynamics. 

PMID- 24880324
TI  - Phase behaviour of liquid-crystal monolayers of rod-like and plate-like
      particles.
AB  - Orientational and positional ordering properties of liquid crystal monolayers are
      examined by means of Fundamental-Measure Density Functional Theory. Particles
      forming the monolayer are modeled as hard parallelepipeds of square section of
      size sigma and length L. Their shapes are controlled by the aspect ratio kappa =
      L/sigma (>1 for prolate and <1 for oblate shapes). The particle centers of mass
      are restricted to a flat surface and three possible and mutually perpendicular
      orientations (in-plane and along the layer normal) of their uniaxial axes are
      allowed. We find that the structure of the monolayer depends strongly on particle
      shape and density. In the case of rod-like shapes, particles align along the
      layer normal in order to achieve the lowest possible occupied area per particle.
      This phase is a uniaxial nematic even at very low densities. In contrast, for
      plate-like particles, the lowest occupied area can be achieved by random in-plane
      ordering in the monolayer, i.e., planar nematic ordering takes place even at
      vanishing densities. It is found that the random in-plane ordering is not
      favorable at higher densities and the system undergoes an in-plane ordering
      transition forming a biaxial nematic phase or crystallizes. For certain values of
      the aspect ratio, the uniaxial-biaxial nematic phase transition is observed for
      both rod-like and plate-like shapes. The stability region of the biaxial nematic
      phase enhances with decreasing aspect ratios for plate-like particles, while the
      rod-like particles exhibit a reentrant phenomenon, i.e., a sequence of uniaxial
      biaxial-uniaxial nematic ordering with increasing density if the aspect ratio is
      larger than 21.34. In addition to this, packing fraction inversion is observed
      with increasing surface pressure due to the alignment along the layers normal. At
      very high densities the nematic phase destabilizes to a nonuniform phases
      (columnar, smectic, or crystalline phases) for both shapes. 

PMID- 24880325
TI  - Low temperature spectral dynamics of single molecules in ultrathin polymer films.
AB  - We studied the spectral dynamics of single fluorescent dye molecules embedded in
      ultrathin films (5 - 100 nm) of the amorphous polymer polyisobutylene at
      cryogenic temperatures and its variation with film thickness. Noticeable portion
      of molecules in the ensemble shows a behavior which is inconsistent with the
      standard tunneling model: Their spectral lines are subject to irreversible
      spectral jumps, continuous shifting, and abrupt chaotic changes of the linewidth
      or jumping rate. In films thinner than 100 nm, the occurrence of "non-standard"
      spectral behavior increases with decreasing sample thickness at fixed excitation
      intensity. In addition, it also increases with laser intensity. 

PMID- 24880326
TI  - Coil-bridge transition in a single polymer chain as an unconventional phase
      transition: theory and simulation.
AB  - The coil-bridge transition in a self-avoiding lattice chain with one end fixed at
      height H above the attractive planar surface is investigated by theory and Monte
      Carlo simulation. We focus on the details of the first-order phase transition
      between the coil state at large height H ? Htr and a bridge state at H ? Htr,
      where Htr corresponds to the coil-bridge transition point. The equilibrium
      properties of the chain were calculated using the Monte Carlo pruned-enriched
      Rosenbluth method in the moderate adsorption regime at (H/Na)tr ? 0.27 where N is
      the number of monomer units of linear size a. An analytical theory of the coil
      bridge transition for lattice chains with excluded volume interactions is
      presented in this regime. The theory provides an excellent quantitative
      description of numerical results at all heights, 10 ? H/a ? 320 and all chain
      lengths 40 < N < 2560 without free fitting parameters. A simple theory taking
      into account the effect of finite extensibility of the lattice chain in the
      strong adsorption regime at (H/Na)tr ? 0.5 is presented. We discuss some
      unconventional properties of the coil-bridge transition: the absence of phase
      coexistence, two micro-phases involved in the bridge state, and abnormal behavior
      in the microcanonical ensemble. 

PMID- 24880327
TI  - Localization and stretching of polymer chains at the junction of two surfaces.
AB  - We present a molecular dynamics study on the stretching of a linear polymer chain
      that is adsorbed at the junction of two intersecting flat surfaces of varying
      alignments. We observe a transition from a two-dimensional to one-dimensional
      (1D) structure of the adsorbed polymer when the alignment, i.e., the angle
      between the two surfaces that form a groove, theta, is below 135 degrees . We
      show that the radius of gyration of the polymer chain Rg scales as Rg ~ N(3/4)
      with the degree of polymerization N for theta = 180 degrees  (planer substrate),
      and the scaling changes to Rg ~ N(1.0) for theta < 135 degrees  in good solvents.
      At the crossover point, theta = 135 degrees , the exponent becomes 1.15. The 1D
      stretching of the polymer chain is found to be 84% of its contour length for
      theta ? 90 degrees . The center of mass diffusion coefficient D decreases sharply
      with theta. However, the diffusion coefficient scales with N as D ~ N(-1), and is
      independent of theta. The relaxation time tau, for the diffusive motion, scales
      as tau ~ N(2.5) for theta = 180 degrees  (planar substrate), which changes to tau
      ~ N(3.0) for theta ? 90 degrees . At the crossover point, the exponent is 3.4,
      which is slightly higher than the 1D value of 3.0. Further, a signature of
      reptation-like dynamics of the polymer chain is observed at the junction for
      theta ? 90 degrees  due to its strong 1D localization and stretching. 

PMID- 24880329
TI  - Percolation in polydisperse systems of aligned rods: a lattice-based analysis.
AB  - A model is developed for percolation in polydisperse systems of oriented
      cylinders that integrates excluded volume arguments with an analogy to site
      percolation on a modified Bethe lattice. Results from this treatment are
      presented for the volume fraction at the percolation threshold (denoted phic) as
      a function of the degree of polydispersity, mixture composition, and degree of
      orientational ordering. For monodisperse systems, phic is found to be a
      monotonically increasing function of the traditional orientational order
      parameter that quantifies degree of alignment. The presence of a fraction of
      isotropically oriented rods of small aspect ratio is shown to lower the
      percolation threshold for systems in which the longer rods are strongly aligned. 

PMID- 24880328
TI  - Size-exclusion partitioning of neutral solutes in crosslinked polymer networks: a
      Monte Carlo simulation study.
AB  - In this work, the size-exclusion partitioning of neutral solutes in crosslinked
      polymer networks has been studied through Monte Carlo simulations. Two models
      that provide user-friendly expressions to predict the partition coefficient have
      been tested over a wide range of volume fractions: Ogston's model (especially
      devised for fibrous media) and the pore model. The effects of crosslinking and
      bond stiffness have also been analyzed. Our results suggest that the fiber model
      can acceptably account for size-exclusion effects in crosslinked gels. Its
      predictions are good for large solutes if the fiber diameter is assumed to be the
      effective monomer diameter. For solutes sizes comparable to the monomer
      dimensions, a smaller fiber diameter must be used. Regarding the pore model, the
      partition coefficient is poorly predicted when the pore diameter is estimated as
      the distance between adjacent crosslinker molecules. On the other hand, our
      results prove that the pore sizes obtained from the pore model by fitting
      partitioning data of swollen gels are overestimated. 

PMID- 24880330
TI  - The adsorption-desorption transition of double-stranded DNA interacting with an
      oppositely charged dendrimer induced by multivalent anions.
AB  - The adsorption-desorption transition of DNA in DNA-dendrimer solutions is
      observed when high-valence anions, such as hexavalent anions, are added to the
      DNA-dendrimer solutions. In the DNA-dendrimer solutions with low-valence anions,
      dendrimers bind tightly with the V-shaped double-stranded DNA. When high-valence
      anions, such as pentavalent or hexavalent anions, are added to the DNA-dendrimer
      solutions, the double-stranded DNA chains can be stretched straightly and the
      dendrimers are released from the double-stranded DNA chains. In fact, adding high
      valence anions to the solutions can change the charge spatial distribution in the
      DNA-dendrimer solutions, and weaken the electrostatic interactions between the
      positively charged dendrimers and the oppositely charged DNA chains. Adsorption
      desorption transition of DNA is induced by the overcharging of dendrimers. This
      investigation is capable of helping us understand how to control effectively the
      release of DNA in gene/drug delivery because an effective gene delivery for
      dendrimers includes non-covalent DNA-dendrimer binding and the effective release
      of DNA in gene therapy. 

PMID- 24880331
TI  - An analytical coarse-graining method which preserves the free energy, structural
      correlations, and thermodynamic state of polymer melts from the atomistic to the
      mesoscale.
AB  - Structural and thermodynamic consistency of coarse-graining models across
      multiple length scales is essential for the predictive role of multi-scale
      modeling and molecular dynamic simulations that use mesoscale descriptions. Our
      approach is a coarse-grained model based on integral equation theory, which can
      represent polymer chains at variable levels of chemical details. The model is
      analytical and depends on molecular and thermodynamic parameters of the system
      under study, as well as on the direct correlation function in the k -> 0 limit,
      c0. A numerical solution to the PRISM integral equations is used to determine c0,
      by adjusting the value of the effective hard sphere diameter, dHS, to agree with
      the predicted equation of state. This single quantity parameterizes the coarse
      grained potential, which is used to perform mesoscale simulations that are
      directly compared with atomistic-level simulations of the same system. We test
      our coarse-graining formalism by comparing structural correlations, isothermal
      compressibility, equation of state, Helmholtz and Gibbs free energies, and
      potential energy and entropy using both united atom and coarse-grained
      descriptions. We find quantitative agreement between the analytical formalism for
      the thermodynamic properties, and the results of Molecular Dynamics simulations,
      independent of the chosen level of representation. In the mesoscale description,
      the potential energy of the soft-particle interaction becomes a free energy in
      the coarse-grained coordinates which preserves the excess free energy from an
      ideal gas across all levels of description. The structural consistency between
      the united-atom and mesoscale descriptions means the relative entropy between
      descriptions has been minimized without any variational optimization parameters.
      The approach is general and applicable to any polymeric system in different
      thermodynamic conditions. 

PMID- 24880332
TI  - Effect of knots on binding of intercalators to DNA.
AB  - We study the effect of knots in circular dsDNA molecules on the binding of
      intercalating ligands. Using Monte Carlo simulations we show that depending on
      their handedness, the presence of knots can either suppress or enhance
      intercalation in supercoiled DNA. When the occupancy of intercalators on DNA is
      low, the effect of knots on intercalation can be captured by introducing a shift
      in the mean writhe of the chain that accounts for the writhe of the corresponding
      ideal knot. In the limit of high intercalator occupancy, the writhe distribution
      of different knots is strongly affected by excluded volume effects and therefore
      by salt concentration. Based on the finding that different knots yield well
      separated probability distributions of bound intercalators, we propose a new
      experimental approach to determine DNA topology by monitoring the intensity of
      fluorescence emitted by dye molecules intercalated into knotted DNA molecules. 

PMID- 24880333
TI  - Molecular ageing: free radical initiated epimerization of thymopentin--a case
      study.
AB  - The epimerization of amino acid residues increases with age in living organisms.
      In the present study, the structural consequences and thermodynamic functions of
      the epimerization of thymopentin (TP-5), the active site of the thymic hormone
      thymopoietin, were studied using molecular dynamics and density functional theory
      methods. The results show that free radical-initiated D-amino acid formation is
      energetically favoured (-130 kJmol(-1)) for each residue and induces significant
      changes to the peptide structure. In comparison to the wild-type (each residue in
      the L-configuration), the radius of gyration of the D-Asp(3) epimer of the
      peptide decreased by 0.5 A, and disrupted the intramolecular hydrogen bonding of
      the native peptide. Beyond establishing important structural, energetic and
      thermodynamic benchmarks and reference data for the structure of TP-5, these
      results disseminate the understanding of molecular ageing, the epimerization of
      amino acid residues. 

PMID- 24880334
TI  - Competition between photodetachment and autodetachment of the 2(1)pipi* state of
      the green fluorescent protein chromophore anion.
AB  - Using a combination of photoelectron spectroscopy measurements and quantum
      chemistry calculations, we have identified competing electron emission processes
      that contribute to the 350-315 nm photoelectron spectra of the deprotonated green
      fluorescent protein chromophore anion, p-hydroxybenzylidene-2,3
      dimethylimidazolinone. As well as direct electron detachment from S0, we observe
      resonant excitation of the 2(1)pipi* state of the anion followed by
      autodetachment. The experimental photoelectron spectra are found to be
      significantly broader than photoelectron spectrum calculated using the Franck
      Condon method and we attribute this to rapid (~10 fs) vibrational decoherence, or
      intramolecular vibrational energy redistribution, within the neutral radical. 

PMID- 24880335
TI  - Oscillations in probability distributions for stochastic gene expression.
AB  - The phenomenon of oscillations in probability distribution functions of number of
      components is found for a model of stochastic gene expression. It takes place in
      cases of low levels of molecules or strong intracellular noise. The oscillations
      distinguish between more probable even and less probable odd number of particles.
      The even-odd symmetry restores as the number of molecules increases with the
      probability distribution function tending to Poisson distribution. We discuss the
      possibility of observation of the phenomenon in gene, protein, and mRNA
      expression experiments. 

PMID- 24880338
TI  - Verbal and visuospatial working memory as predictors of children's reading
      ability.
AB  - Children with reading difficulties often demonstrate weaknesses in working memory
      (WM). This research study explored the relation between two WM systems (verbal
      and visuospatial WM) and reading ability in a sample of school-aged children with
      a wide range of reading skills. Children (N = 157), ages 9-12, were administered
      measures of short-term memory, verbal WM, visuospatial WM, and reading measures
      (e.g., reading fluency and comprehension). Although results indicated that verbal
      WM was a stronger predictor in reading fluency and comprehension, visuospatial WM
      also significantly predicted reading skills, but provided more unique variance in
      reading comprehension than reading fluency. These findings suggest that
      visuospatial WM may play a significant role in higher level reading processes,
      particularly in reading comprehension, than previously thought. 

PMID- 24880337
TI  - OPT3 is a component of the iron-signaling network between leaves and roots and
      misregulation of OPT3 leads to an over-accumulation of cadmium in seeds.
AB  - Plants and seeds are the main dietary sources of zinc, iron, manganese, and
      copper, but are also the main entry point for toxic elements such as cadmium into
      the food chain. We report here that an Arabidopsis oligopeptide transporter
      mutant, opt3-2, over-accumulates cadmium (Cd) in seeds and roots but,
      unexpectedly, under-accumulates Cd in leaves. The cadmium distribution in opt3-2
      differs from iron, zinc, and manganese, suggesting a metal-specific mechanism for
      metal partitioning within the plant. The opt3-2 mutant constitutively up
      regulates the Fe/Zn/Cd transporter IRT1 and FRO2 in roots, indicative of an iron
      deficiency response. No genetic mutants that impair the shoot-to-root signaling
      of iron status in leaves have been identified. Interestingly, shoot-specific
      expression of OPT3 rescues the Cd sensitivity and complements the aberrant
      expression of IRT1 in opt3-2 roots, suggesting that OPT3 is required to relay the
      iron status from leaves to roots. OPT3 expression was found in the vasculature
      with preferential expression in the phloem at the plasma membrane. Using
      radioisotope experiments, we found that mobilization of Fe from leaves is
      severely affected in opt3-2, suggesting that Fe mobilization out of leaves is
      required for proper trace-metal homeostasis. When expressed in yeast, OPT3 does
      not localize to the plasma membrane, precluding the identification of the OPT3
      substrate. Our in planta results show that OPT3 is important for leaf phloem
      loading of iron and plays a key role regulating Fe, Zn, and Cd distribution
      within the plant. Furthermore, ferric chelate reductase activity analyses provide
      evidence that iron is not the sole signal transferred from leaves to roots in
      leaf iron status signaling. 

PMID- 24880339
TI  - A molecular basis for classic blond hair color in Europeans.
AB  - Hair color differences are among the most obvious examples of phenotypic
      variation in humans. Although genome-wide association studies (GWAS) have
      implicated multiple loci in human pigment variation, the causative base-pair
      changes are still largely unknown. Here we dissect a regulatory region of the
      KITLG gene (encoding KIT ligand) that is significantly associated with common
      blond hair color in northern Europeans. Functional tests demonstrate that the
      region contains a regulatory enhancer that drives expression in developing hair
      follicles. This enhancer contains a common SNP (rs12821256) that alters a binding
      site for the lymphoid enhancer-binding factor 1 (LEF1) transcription factor,
      reducing LEF1 responsiveness and enhancer activity in cultured human
      keratinocytes. Mice carrying ancestral or derived variants of the human KITLG
      enhancer exhibit significant differences in hair pigmentation, confirming that
      altered regulation of an essential growth factor contributes to the classic blond
      hair phenotype found in northern Europeans. 

PMID- 24880340
TI  - Identification of erythroferrone as an erythroid regulator of iron metabolism.
AB  - Recovery from blood loss requires a greatly enhanced supply of iron to support
      expanded erythropoiesis. After hemorrhage, suppression of the iron-regulatory
      hormone hepcidin allows increased iron absorption and mobilization from stores.
      We identified a new hormone, erythroferrone (ERFE), that mediates hepcidin
      suppression during stress erythropoiesis. ERFE is produced by erythroblasts in
      response to erythropoietin. ERFE-deficient mice fail to suppress hepcidin rapidly
      after hemorrhage and exhibit a delay in recovery from blood loss. ERFE expression
      is greatly increased in Hbb(th3/+) mice with thalassemia intermedia, where it
      contributes to the suppression of hepcidin and the systemic iron overload
      characteristic of this disease. 

PMID- 24880341
TI  - Exome sequencing identifies somatic gain-of-function PPM1D mutations in brainstem
      gliomas.
AB  - Gliomas arising in the brainstem and thalamus are devastating tumors that are
      difficult to surgically resect. To determine the genetic and epigenetic landscape
      of these tumors, we performed exomic sequencing of 14 brainstem gliomas (BSGs)
      and 12 thalamic gliomas. We also performed targeted mutational analysis of an
      additional 24 such tumors and genome-wide methylation profiling of 45 gliomas.
      This study led to the discovery of tumor-specific mutations in PPM1D, encoding
      wild-type p53-induced protein phosphatase 1D (WIP1), in 37.5% of the BSGs that
      harbored hallmark H3F3A mutations encoding p.Lys27Met substitutions. PPM1D
      mutations were mutually exclusive with TP53 mutations in BSG and attenuated p53
      activation in vitro. PPM1D mutations were truncating alterations in exon 6 that
      enhanced the ability of PPM1D to suppress the activation of the DNA damage
      response checkpoint protein CHK2. These results define PPM1D as a frequent target
      of somatic mutation and as a potential therapeutic target in brainstem gliomas. 

PMID- 24880343
TI  - An asymmetric PAN3 dimer recruits a single PAN2 exonuclease to mediate mRNA
      deadenylation and decay.
AB  - The PAN2-PAN3 complex functions in general and microRNA-mediated mRNA
      deadenylation. However, mechanistic insight into PAN2 and its complex with the
      asymmetric PAN3 dimer is lacking. Here, we describe crystal structures that show
      that Neurospora crassa PAN2 comprises two independent structural units: a C
      terminal catalytic unit and an N-terminal assembly unit that engages in a
      bipartite interaction with PAN3 dimers. The catalytic unit contains the
      exonuclease domain in an intimate complex with a potentially modulatory ubiquitin
      protease-like domain. The assembly unit contains a WD40 propeller connected to an
      adaptable linker. The propeller contacts the PAN3 C-terminal domain, whereas the
      linker reinforces the asymmetry of the PAN3 dimer and prevents the recruitment of
      a second PAN2 molecule. Functional data indicate an essential role for PAN3 in
      coordinating PAN2-mediated deadenylation with subsequent steps in mRNA decay,
      which lead to complete mRNA degradation. 

PMID- 24880345
TI  - Randomized controlled multicenter trial on the effectiveness of the collagen
      hemostat Sangustop(r) compared with a carrier-bound fibrin sealant during liver
      resection (ESSCALIVER study, NCT00918619).
AB  - BACKGROUND: Despite improvements in liver surgery over the past decades,
      hemostasis during hepatic resections remains challenging. This multicenter
      randomized study compares the hemostatic effect of a collagen hemostat vs. a
      carrier-bound fibrin sealant after hepatic resection. METHODS: Patients scheduled
      for elective liver resection were randomized intraoperatively to receive either
      the collagen hemostat (COLL) or the carrier-bound fibrin sealant (CBFS) for
      secondary hemostasis. The primary endpoint was the proportion of patients with
      hemostasis after 3 min. Secondary parameters were the proportions of patients
      with hemostasis after 5 and 10 min, the total time to hemostasis, and the
      complication rates during a 3 months follow-up period. RESULTS: A total of 128
      patients were included. In the COLL group, 53 out of 61 patients (86.9 %)
      achieved complete hemostasis within 3 min after application of the hemostat
      compared to 52 out of 65 patients (80.0 %) in the CBFS group. The 95 % confidence
      interval for this difference [-6.0 %, 19.8 %] does not include the lower
      noninferiority margin (-10 %). Thus, the COLL treatment can be regarded as
      noninferior to the comparator. The proportions of patients with hemostasis after
      3, 5, and 10 min were not significantly different between the two study arms.
      Postoperative mortality and morbidity were similar in both treatment groups.
      CONCLUSION: The collagen hemostat is as effective as the carrier-bound fibrin
      sealant in obtaining secondary hemostasis during liver resection with a
      comparable complication rate.

PMID- 24880344
TI  - The structure of the Pan2-Pan3 core complex reveals cross-talk between
      deadenylase and pseudokinase.
AB  - Pan2-Pan3 is a conserved complex involved in the shortening of mRNA poly(A)
      tails, the initial step in eukaryotic mRNA turnover. We show that recombinant
      Saccharomyces cerevisiae Pan2-Pan3 can deadenylate RNAs in vitro without needing
      the poly(A)-binding protein Pab1. The crystal structure of an active ~200-kDa
      core complex reveals that Pan2 and Pan3 interact with an unusual 1:2
      stoichiometry imparted by the asymmetric nature of the Pan3 homodimer. An
      extended region of Pan2 wraps around Pan3 and provides a major anchoring point
      for complex assembly. A Pan2 module formed by the pseudoubiquitin-hydrolase and
      RNase domains latches onto the Pan3 pseudokinase with intertwined interactions
      that orient the deadenylase active site toward the A-binding site of the
      interacting Pan3. The molecular architecture of Pan2-Pan3 suggests how the
      nuclease and its pseudokinase regulator act in synergy to promote deadenylation. 

PMID- 24880347
TI  - High pressure and temperature optical flow cell for near-infra-red spectroscopic
      analysis of gas mixtures.
AB  - A new optical flow cell with a new optical arrangement adapted for high pressures
      and temperatures using glass fibres to connect light source, cell, and
      spectrometer has been developed, as part of a larger project comprising new
      methods for in situ analysis of bio and hydrogen gas mixtures in high pressure
      and temperature applications. The analysis is based on measurements of optical,
      thermo-physical, and electromagnetic properties in gas mixtures with newly
      developed high pressure property sensors, which are mounted in a new apparatus
      which can generate gas mixtures with up to six components with an uncertainty of
      composition of as little as 0.1 mol. %. Measurements of several pure components
      of natural gases and biogases to a pressure of 20 MPa were performed on two
      isotherms, and with binary mixtures of the same pure gases at pressures to 17.5
      MPa. Thereby a new method of analyzing the obtained spectra based on the partial
      density of methane was investigated. 

PMID- 24880346
TI  - Fibrin sealants and topical agents in hepatobiliary and pancreatic surgery: a
      critical appraisal.
AB  - INTRODUCTION: Fibrin sealants and topical hemostatic agents have been used
      extensively in hepatobiliary and pancreatic (HPB) surgery to promote coagulation
      and clot formation decreasing the need for allogeneic blood transfusion and to
      act as tissue sealants, ideally preventing biliary, enteric, and pancreatic
      leaks. RESULTS: Current literature has demonstrated some favorable outcomes using
      many different products for application in the field of HPB surgery. However,
      critical findings exist demonstrating lack of reproducible efficacy or benefit.
      In all, many clinical trials have demonstrated effectiveness of fibrin sealants
      and other agents at reducing the need for intraoperative and postoperative blood
      transfusion. Ability to effectively seal tissues providing biliostatic effect or
      preventing postoperative fistula formation remains debated as definitive evidence
      is lacking. CONCLUSIONS: In the following invited review, we discuss current
      literature describing the use of topical agents and fibrin sealants in liver and
      pancreas surgery. We summarize major contemporary clinical trials and their
      findings regarding the use of these agents in HPB surgery and provide evidence
      from the preclinical literature as to the translation of these products into the
      clinical arena.

PMID- 24880348
TI  - Magnetic-film atom chip with 10 MUm period lattices of microtraps for quantum
      information science with Rydberg atoms.
AB  - We describe the fabrication and construction of a setup for creating lattices of
      magnetic microtraps for ultracold atoms on an atom chip. The lattice is defined
      by lithographic patterning of a permanent magnetic film. Patterned magnetic-film
      atom chips enable a large variety of trapping geometries over a wide range of
      length scales. We demonstrate an atom chip with a lattice constant of 10 MUm,
      suitable for experiments in quantum information science employing the interaction
      between atoms in highly excited Rydberg energy levels. The active trapping region
      contains lattice regions with square and hexagonal symmetry, with the two regions
      joined at an interface. A structure of macroscopic wires, cutout of a silver
      foil, was mounted under the atom chip in order to load ultracold (87)Rb atoms
      into the microtraps. We demonstrate loading of atoms into the square and
      hexagonal lattice sections simultaneously and show resolved imaging of individual
      lattice sites. Magnetic-film lattices on atom chips provide a versatile platform
      for experiments with ultracold atoms, in particular for quantum information
      science and quantum simulation. 

PMID- 24880349
TI  - Spin-polarized hydrogen Rydberg time-of-flight: experimental measurement of the
      velocity-dependent H atom spin-polarization.
AB  - We have developed a new experimental method allowing direct detection of the
      velocity dependent spin-polarization of hydrogen atoms produced in
      photodissociation. The technique, which is a variation on the H atom Rydberg time
      of-flight method, employs a double-resonance excitation scheme and experimental
      geometry that yields the two coherent orientation parameters as a function of
      recoil speed for scattering perpendicular to the laser propagation direction. The
      approach, apparatus, and optical layout we employ are described here in detail
      and demonstrated in application to HBr and DBr photolysis at 213 nm. We also
      discuss the theoretical foundation for the approach, as well as the resolution
      and sensitivity we achieve. 

PMID- 24880350
TI  - Measurement of modal birefringence in optical waveguides based on the Mach
      Zehnder interferometer.
AB  - A method for measuring the birefringence in planar waveguide circuits is
      theoretically proposed and validated. The method is based on the Mach-Zehnder
      interference and by measuring the spectral shift due to orthogonal polarization
      states. The birefringence of a silica waveguide is measured to be 2.33 * 10(-4)
      at nearby 1550 nm. In addition, the birefringence variations with the wavelength
      and its dependence on the external stress are investigated with the proposed
      method experimentally. The results in measuring birefringence demonstrate a high
      accuracy with the order of 10(-5), a wide dynamic range from 10(-5) to 10(-3),
      and a characteristic of multi-wavelength evaluation. 

PMID- 24880351
TI  - MONSTIR II: a 32-channel, multispectral, time-resolved optical tomography system
      for neonatal brain imaging.
AB  - We detail the design, construction and performance of the second generation UCL
      time-resolved optical tomography system, known as MONSTIR II. Intended primarily
      for the study of the newborn brain, the system employs 32 source fibres that
      sequentially transmit picosecond pulses of light at any four wavelengths between
      650 and 900 nm. The 32 detector channels each contain an independent photo
      multiplier tube and temporally correlated photon-counting electronics that allow
      the photon transit time between each source and each detector position to be
      measured with high temporal resolution. The system's response time, temporal
      stability, cross-talk, and spectral characteristics are reported. The efficacy of
      MONSTIR II is demonstrated by performing multi-spectral imaging of a simple
      phantom. 

PMID- 24880352
TI  - A multichannel magneto-chiral dichroism spectrometer.
AB  - In this work, we describe a multichannel magneto-chiral dichroism spectrometer
      for the visible and near infrared wavelength ranges. The optical signal
      acquisition is based on commercially available Czerny-Turner spectrograph systems
      equipped with solid state detector arrays. The signal analysis method is based on
      post-processing phase sensitive detection, where the optical properties of the
      sample are modulated by an alternating external magnetic field. As an
      illustration of the performance of this spectrometer, magneto-chiral dichroism
      was measured in crystals of alpha - NiSO4 . 6H2O and good agreement with
      literature results was obtained. 

PMID- 24880353
TI  - The development of a portable ultrahigh vacuum chamber via silicon block.
AB  - This paper describes a nonmetallic, light weight portable chamber for ultra-high
      vacuum (UHV) applications. The chamber consists of a processed silicon block
      anodically bonding five polished Pyrex glass windows and a Pyrex glass adapter,
      without using any screws, bolts or vacuum adhesives. The design features provide
      an alternative chamber for UHV applications which require nonmetallic components.
      We have cyclically baked the chamber up to 180  degrees C for 160 h and have
      achieved an ultimate pressure of 1.4 * 10(-9) Torr (limited by our pumping
      station), with no leak detected. Both Pyrex glass windows and Pyrex glass adapter
      have been used successfully.

PMID- 24880354
TI  - Crosstalk elimination in the detection of dual-beam optical tweezers by spatial
      filtering.
AB  - In dual-beam optical tweezers, the accuracy of position and force measurements is
      often compromised by crosstalk between the two detected signals, this crosstalk
      leading to systematic and significant errors on the measured forces and
      distances. This is true both for dual-beam optical traps where the splitting of
      the two traps is done by polarization optics and for dual optical traps
      constructed by other methods, e.g., holographic tweezers. If the two traps are
      orthogonally polarized, most often crosstalk is minimized by inserting
      polarization optics in front of the detector; however, this method is not perfect
      because of the de-polarization of the trapping beam introduced by the required
      high numerical aperture optics. Here we present a simple and easy-to-implement
      method to efficiently eliminate crosstalk. The method is based on spatial
      filtering by simply inserting a pinhole at the correct position and is highly
      compatible with standard back focal plane photodiode based detection of position
      and force. Our spatial filtering method reduces crosstalk up to five times better
      than polarization filtering alone. The effectiveness is dependent on pinhole size
      and distance between the traps and is here quantified experimentally and
      reproduced by theoretical modeling. The method here proposed will improve the
      accuracy of force-distance measurements, e.g., of single molecules, performed by
      dual-beam optical traps and hence give much more scientific value for the
      experimental efforts. 

PMID- 24880355
TI  - Mode imaging and loss evaluation of semiconductor waveguides.
AB  - An imaging and loss evaluation method for semiconductor waveguides coupled with
      non-doped quantum wells is presented. Using the internal emission of the wells as
      a probe light source, the numbers and widths of the modes of waveguides with
      various ridge sizes were evaluated by CCD imaging, and the obtained values were
      consistent with effective index method calculation. Waveguide internal losses
      were obtained from analyses of the Fabry-Perot fringes of waveguide emission
      spectra. We quantified the quality of 29 single-mode waveguide samples as an
      internal loss and variation of 10.2 +/- 0.6  cm(-1).

PMID- 24880356
TI  - A novel von Hamos spectrometer for efficient X-ray emission spectroscopy in the
      laboratory.
AB  - We present a novel, highly efficient von Hamos spectrometer for X-ray emission
      spectroscopy (XES) in the laboratory using highly annealed pyrolitic graphite
      crystals as the dispersive element. The spectrometer covers an energy range from
      2.5 keV to 15 keV giving access to chemical speciation and information about the
      electronic configuration of 3d transition metals by means of the Kbeta multiplet.
      XES spectra of Ti compounds are presented to demonstrate the speciation
      capabilities of the instrument. A spectral resolving power of E/DeltaE = 2000 at
      8 keV was achieved. Typical acquisition times range from 10 min for bulk material
      to hours for thin samples below 1 MUm.

PMID- 24880342
TI  - Rare variants of large effect in BRCA2 and CHEK2 affect risk of lung cancer.
AB  - We conducted imputation to the 1000 Genomes Project of four genome-wide
      association studies of lung cancer in populations of European ancestry (11,348
      cases and 15,861 controls) and genotyped an additional 10,246 cases and 38,295
      controls for follow-up. We identified large-effect genome-wide associations for
      squamous lung cancer with the rare variants BRCA2 p.Lys3326X (rs11571833, odds
      ratio (OR) = 2.47, P = 4.74 * 10(-20)) and CHEK2 p.Ile157Thr (rs17879961, OR =
      0.38, P = 1.27 * 10(-13)). We also showed an association between common variation
      at 3q28 (TP63, rs13314271, OR = 1.13, P = 7.22 * 10(-10)) and lung adenocarcinoma
      that had been previously reported only in Asians. These findings provide further
      evidence for inherited genetic susceptibility to lung cancer and its biological
      basis. Additionally, our analysis demonstrates that imputation can identify rare
      disease-causing variants with substantive effects on cancer risk from preexisting
      genome-wide association study data. 

PMID- 24880357
TI  - A cavity ring-down spectroscopy sensor for real-time Hall thruster erosion
      measurements.
AB  - A continuous-wave cavity ring-down spectroscopy sensor for real-time measurements
      of sputtered boron from Hall thrusters has been developed. The sensor uses a
      continuous-wave frequency-quadrupled diode laser at 250 nm to probe ground state
      atomic boron sputtered from the boron nitride insulating channel. Validation
      results from a controlled setup using an ion beam and target showed good
      agreement with a simple finite-element model. Application of the sensor for
      measurements of two Hall thrusters, the H6 and SPT-70, is described. The H6 was
      tested at power levels ranging from 1.5 to 10 kW. Peak boron densities of 10 +/-
      2 * 10(14) m(-3) were measured in the thruster plume, and the estimated eroded
      channel volume agreed within a factor of 2 of profilometry. The SPT-70 was tested
      at 600 and 660 W, yielding peak boron densities of 7.2 +/- 1.1 * 10(14) m(-3),
      and the estimated erosion rate agreed within ~20% of profilometry. Technical
      challenges associated with operating a high-finesse cavity in the presence of
      energetic plasma are also discussed.

PMID- 24880358
TI  - An inverted cylindrical sputter magnetron as metal vapor supply for electron
      cyclotron resonance ion sources.
AB  - An inverted cylindrical sputter magnetron device has been developed. The
      magnetron is acting as a metal vapor supply for an electron cyclotron resonance
      (ECR) ion source. FEM simulation of magnetic flux density was used to ensure that
      there is no critical interaction between both magnetic fields of magnetron and
      ECR ion source. Spatially resolved double Langmuir probe and optical emission
      spectroscopy measurements show an increase in electron density by one order of
      magnitude from 1 * 10(10) cm(-3) to 1 * 10(11) cm(-3), when the magnetron plasma
      is exposed to the magnetic mirror field of the ECR ion source. Electron density
      enhancement is also indicated by magnetron plasma emission photography with a CCD
      camera. Furthermore, photographs visualize the formation of a localized loss-cone
      - area, when the magnetron is operated at magnetic mirror field conditions. The
      inverted cylindrical magnetron supplies a metal atom load rate of R > 1 * 10(18)
      atoms/s for aluminum, which meets the demand for the production of a milliampere
      Al(+) ion beam.

PMID- 24880359
TI  - Jitter characteristic of series magnetic pulse compressor employed in ns trigger
      generator.
AB  - The jitter characteristic of series magnetic pulse compressor (MPC) employed in
      ns trigger generator was explored. The time delay of the series MPC is the sum
      value of the compression time in each stage. The primary voltage disturbance is
      the original parameter to affect the timing stability of the system. Decreasing
      the relative jitter of the primary voltage and the first compression time are the
      practical and exclusive approaches to decrease to time jitter of the series MPC.
      The jitter experiment was carried out on the three-stage series MPC charged with
      a fast step-up LC transformer. The performance data show that the delay time
      decreases with the increase of primary voltage. Meanwhile, the measured ratio
      between the time jitter and the relative jitter of the primary voltage accords
      with the theoretical result. 

PMID- 24880360
TI  - Superconducting magnetic Wollaston prism for neutron spin encoding.
AB  - A magnetic Wollaston prism can spatially split a polarized neutron beam into two
      beams with different neutron spin states, in a manner analogous to an optical
      Wollaston prism. Such a Wollaston prism can be used to encode the trajectory of
      neutrons into the Larmor phase associated with their spin degree of freedom. This
      encoding can be used for neutron phase-contrast radiography and in spin echo
      scattering angle measurement (SESAME). In this paper, we show that magnetic
      Wollaston prisms with highly uniform magnetic fields and low Larmor phase
      aberration can be constructed to preserve neutron polarization using high
      temperature superconducting (HTS) materials. The Meissner effect of HTS films is
      used to confine magnetic fields produced electromagnetically by current-carrying
      HTS tape wound on suitably shaped soft iron pole pieces. The device is cooled to
      ~30 K by a closed cycle refrigerator, eliminating the need to replenish liquid
      cryogens and greatly simplifying operation and maintenance. A HTS film ensures
      that the magnetic field transition within the prism is sharp, well-defined, and
      planar due to the Meissner effect. The spin transport efficiency across the
      device was measured to be ~98.5% independent of neutron wavelength and energizing
      current. The position-dependent Larmor phase of neutron spins was measured at the
      NIST Center for Neutron Research facility and found to agree well with detailed
      simulations. The phase varies linearly with horizontal position, as required, and
      the neutron beam shows little depolarization. Consequently, the device has
      advantages over existing devices with similar functionality and provides the
      capability for a large neutron beam (20 mm * 30 mm) and an increase in length
      scales accessible to SESAME to beyond 10 MUm. With further improvements of the
      external coupling guide field in the prototype device, a larger neutron beam
      could be employed.

PMID- 24880361
TI  - Effect of the fissile bead's and thermocouple wires' sizes on the response time
      of a fission couple.
AB  - The fission couple is proposed as a fast response miniature neutron detector in
      the measurement of time dependent energy depositions within the fissile material
      based on theoretical analysis, but the response time of a fission couple is
      relatively slow in practice. The time lag originated from heat transfer process
      was demonstrated to be the dominating factor by theoretical simulations and
      experimental verification in this paper. The response of a fission couple as a
      function of the bead size and the thermocouple wires' sizes are simulated using
      ANSYS workbench. The decrease of wires' diameter results in the decrease of
      response time, and the increase of bead's diameter leads to a slight increase of
      response time. During a pulse heating transient in the fuel of Chinese Fast Burst
      Reactor II with a FWHM of 181 MUs, the time lag originated from heat transfer
      process is about tens of microseconds for the peaks of the change rate of
      temperature, and is of the order of milliseconds to achieve 85% of the
      temperature rise for a typical fission couple with a Phi 1 mm fissile bead and
      two Phi 0.05 mm thermocouple wires. The results obtained provide foundation for
      the optimization of fission couples.

PMID- 24880363
TI  - Capacitances and energy deposition curve of nanosecond pulse surface dielectric
      barrier discharge plasma actuator.
AB  - Nanosecond pulse surface dielectric barrier discharge (NPSDBD) plasma actuator is
      preferred to generate aerodynamic actuation which relies on the deposited energy
      during nanosecond time scale, named as the mechanism of fast thermalization. It
      is very important to understand the energy deposition process of NPSDBD plasma
      actuator. In this paper, an equivalent circuit model is presented to describe a
      typical asymmetric NPSDBD plasma actuator first. Of the three key capacitances in
      the equivalent circuit, the values of Capacitance C(m) and C(g) can be gotten by
      the calculation of the electric field, with the method of undetermined
      coefficients, while the value of Capacitance C(d) is determined from the charge
      voltage (Q-V) plot, also called Lissajous figure. It is found that the value of
      Capacitance C(d) varies with the amplitude of applied pulse voltage, due to the
      change of the dimension of plasma sheet. Based on the circuit parameters and the
      measured waveforms of discharge voltage and current, the time varying
      characteristics of deposited energy can be obtained finally. It is indicated that
      the calculated results of deposited energy show a good agreement with
      conventional method.

PMID- 24880362
TI  - Nuclear and in-source laser spectroscopy with the ISAC yield station.
AB  - A new decay station has been built for the ISAC facility at TRIUMF for the rapid
      and reliable characterization of radioactive ion beam (RIB) compositions and
      intensities with the capability of simultaneously collecting alpha, beta, and
      gamma decay data from RIB with intensities between a few and ~10(11) ions per
      second. It features user-friendly control, data acquisition, and analysis
      software. The analysis of individual decay time structures allows the unambiguous
      assignment of alpha and gamma lines even with substantial isobaric contamination
      present. The capability for accurate half-life measurements is demonstrated with
      the example of (46)K. The coupling of the yield station to the laser ion source,
      TRILIS, allows the correlation of radiometric data with automated laser frequency
      scans. First results of in-source laser spectroscopy measurements on astatine are
      discussed. 

PMID- 24880364
TI  - Development of the scintillator-based probe for fast-ion losses in the HL-2A
      tokamak.
AB  - A new scintillator-based lost fast-ion probe (SLIP) has been developed and
      operated in the HL-2A tokamak [L. W. Yan, X. R. Duan, X. T. Ding, J. Q. Dong, Q.
      W. Yang, Yi Liu, X. L. Zou, D. Q. Liu, W. M. Xuan, L. Y. Chen, J. Rao, X. M.
      Song, Y. Huang, W. C. Mao, Q. M. Wang, Q. Li, Z. Cao, B. Li, J. Y. Cao, G. J.
      Lei, J. H. Zhang, X. D. Li, W. Chen, J. Chen, C. H. Cui, Z. Y. Cui, Z. C. Deng,
      Y. B. Dong, B. B. Feng, Q. D. Gao, X. Y. Han, W. Y. Hong, M. Huang, X. Q. Ji, Z.
      H. Kang, D. F. Kong, T. Lan, G. S. Li, H. J. Li, Qing Li, W. Li, Y. G. Li, A. D.
      Liu, Z. T. Liu, C. W. Luo, X. H. Mao, Y. D. Pan, J. F. Peng, Z. B. Shi, S. D.
      Song, X. Y. Song, H. J. Sun, A. K. Wang, M. X. Wang, Y. Q. Wang, W. W. Xiao, Y.
      F. Xie, L. H. Yao, D. L. Yu, B. S. Yuan, K. J. Zhao, G. W. Zhong, J. Zhou, J. C.
      Yan, C. X. Yu, C. H. Pan, Y. Liu, and the HL-2A Team, Nucl. Fusion 51, 094016
      (2011)] to measure the losses of neutral beam ions. The design of the probe is
      based on the concept of the alpha-particle detectors on Tokamak Fusion Test
      Reactor (TFTR) using scintillator plates. The probe is capable of traveling
      across an equatorial plane port and sweeping the aperture angle rotationally with
      respect to the axis of the probe shaft by two step motors, in order to optimize
      the radial position and the collimator angle. The energy and the pitch angle of
      the lost fast ions can be simultaneously measured if the two-dimensional image of
      scintillation light intensity due to the impact of the lost fast ions is
      detected. Measurements of the fast-ion losses using the probe have been performed
      during HL-2A neutral beam injection discharges. The clear experimental evidence
      of enhanced losses of beam ions during disruptions has been obtained by means of
      the SLIP system. A detailed description of the probe system and the first
      experimental results are reported. 

PMID- 24880365
TI  - Characterization and calibration of 8-channel E-band heterodyne radiometer system
      for SST-1 tokamak.
AB  - An 8-channel E-band heterodyne radiometer system (74-86 GHz) is designed,
      characterized, and calibrated to measure the radial electron temperature profile
      by measuring Electron Cyclotron Emission spectrum at SST-1 Tokamak. The developed
      radiometer has a noise equivalent temperature of 1 eV and sensitivity of 5 *
      10(9) V/W. In order to precisely measure the absolute value of electron
      temperature, a calibration measurement of the radiometer system is performed
      using hot-cold Dicke switch method, which confirms the system linearity. 

PMID- 24880366
TI  - The construction of an electrode biasing system for driving plasma rotation in J
      TEXT tokamak.
AB  - A newly designed electrode biasing system has been constructed for driving plasma
      rotation in J-TEXT tokamak. To reduce the influence to the plasma, the system
      contains a pneumatic driving system so that it can reciprocate in a single
      discharge, with a stroke of about 5 cm in 100 ms. The power supply of the system
      can provide stable and adjustable dc voltage in the range of 0-700 V, with
      adjustable duration of 10-200 ms; its instantaneous power output can reach up to
      more than 200 kW. In addition, the power supply can also provide a multi-cycle
      voltage waveform, with adjustable pulse width and voltage amplitude. When
      applying a positive bias to the plasma, both an improvement of plasma confinement
      and the speed-up of plasma-edge toroidal rotation in the same direction of plasma
      current are observed in the experiments. 

PMID- 24880367
TI  - Robotic calibration of the motional Stark effect diagnostic on Alcator C-Mod.
AB  - The capability to calibrate diagnostics, such as the Motional Stark Effect (MSE)
      diagnostic, without using plasma or beam-into-gas discharges will become
      increasingly important on next step fusion facilities due to machine availability
      and operational constraints. A robotic calibration system consisting of a
      motorized three-axis positioning system and a polarization light source capable
      of generating arbitrary polarization states with a linear polarization angle
      accuracy of <0.05 degrees  has been constructed and has been used to calibrate
      the MSE diagnostic deployed on Alcator C-Mod. The polarization response of the
      complex diagnostic is shown to be fully captured using a Fourier expansion of the
      detector signals in terms of even harmonics of the input polarization angle. The
      system's high precision robotic control of position and orientation allow it to
      be used also to calibrate the geometry of the instrument's view. Combined with
      careful measurements of the narrow bandpass spectral filters, this system fully
      calibrates the diagnostic without any plasma discharges. The system's high
      repeatability, flexibility, and speed has been exploited to quantify several
      systematics in the MSE diagnostic response, providing a more complete
      understanding of the diagnostic performance. 

PMID- 24880369
TI  - On the use of the double floating probe method to infer the difference between
      the electron and the heavy particles temperatures in an atmospheric pressure,
      vortex-stabilized nitrogen plasma jet.
AB  - Sweeping double probe measurements in an atmospheric pressure direct current
      vortex-stabilized plasma jet are reported (plasma conditions: 100 A discharge
      current, N2 gas flow rate of 25 Nl/min, thoriated tungsten rod-type cathode,
      copper anode with 5 mm inner diameter). The interpretation of the double probe
      characteristic was based on a generalization of the standard double floating
      probe formulae for non-uniform plasmas coupled to a non-equilibrium plasma
      composition model. Perturbations caused by the current to the probe together with
      collisional and thermal processes inside the probe perturbed region were taken
      into account. Radial values of the average electron and heavy particle
      temperatures as well as the electron density were obtained. The calculation of
      the temperature values did not require any specific assumption about a
      temperature relationship between different particle species. An electron
      temperature of 10,900 +/- 900 K, a heavy particle temperature of 9300 +/- 900 K,
      and an electron density of about 3.5 * 10(22) m(-3) were found at the jet centre
      at 3.5 mm downstream from the torch exit. Large deviations from kinetic
      equilibrium were found toward the outer border of the plasma jet. These results
      showed good agreement with those previously reported by the authors by using a
      single probe technique. The calculations have shown that this method is
      particularly useful for studying spraying-type plasma torches operated at power
      levels of about 15 kW.

PMID- 24880368
TI  - A novel electron density reconstruction method for asymmetrical toroidal plasmas.
AB  - A novel reconstruction method is developed for acquiring the electron density
      profile from multi-channel interferometric measurements of strongly asymmetrical
      toroidal plasmas. It is based on a regularization technique, and a generalized
      cross-validation function is used to optimize the regularization parameter with
      the aid of singular value decomposition. The feasibility of method could be
      testified by simulated measurements based on a magnetic configuration of the
      flexible helical-axis heliotron device, Heliotron J, which has an asymmetrical
      poloidal cross section. And the successful reconstruction makes possible to
      construct a multi-channel Far-infrared laser interferometry on this device. The
      advantages of this method are demonstrated by comparison with a conventional
      method. The factors which may affect the accuracy of the results are
      investigated, and an error analysis is carried out. Based on the obtained
      results, the proposed method is highly promising for accurately reconstructing
      the electron density in the asymmetrical toroidal plasma. 

PMID- 24880370
TI  - The motional Stark effect polarimeter in the HL-2A tokamak.
AB  - A 7-channel motional Stark effect polarimeter based on four polarizers and a
      spectrometer has been developed in the HL-2A tokamak, which is the first time
      successful utilizing this kind of polarimeter on a tokamak. The accuracy of the
      angle can reach +/-0.25 degrees  in the calibration experiments. Pilot
      experiments of measuring the magnetic pitch angle have been successfully carried
      out in the weak motional Stark effect plasma discharge with toroidal magnetic
      field of ~1.3 T and beam energy of ~25 keV/amu. The pitch angles of magnetic
      field are obtained for 7 spatial points covering 24 cm along major radius with
      time resolution of 40 ms; the profiles of safety factor are obtained by combining
      with the Equilibrium and Reconstruction Fitting Code. The core value of safety
      factor (q) is less than 1 during the sawtooth oscillation and the position of q =
      1 surface is well consistent with the results measured by soft X-ray array.

PMID- 24880371
TI  - Study of runaway electrons using dosimetry of hard x-ray radiations in Damavand
      tokamak.
AB  - In this work several studies have been conducted on hard x-ray emissions of
      Damavand tokamak based on radiation dosimetry using the Thermoluminescence
      method. The goal was to understand interactions of runaway electrons with plasma
      particles, vessel wall, and plasma facing components. Total of 354 GR-200
      (LiF:Mg,Cu,P) thermoluminescence dosimeter (TLD) crystals have been placed on 118
      points--three TLDs per point--to map hard x-ray radiation doses on the exterior
      of the vacuum vessel. Results show two distinctive levels of x-ray radiations
      doses on the exterior of the vessel. The low-dose area on which measured dose is
      about 0.5 mSv/shot. In the low-dose area there is no particular component inside
      the vessel. On the contrary, on high-dose area of the vessel, x-ray radiations
      dose exceeds 30 mSv/shot. The high-dose area coincides with the position of
      limiters, magnetic probe ducts, and vacuum vessel intersections. Among the high
      dose areas, the highest level of dose is measured in the position of the limiter,
      which could be due to its direct contact with the plasma column and with runaway
      electrons. Direct collisions of runaway electrons with the vessel wall and plasma
      facing components make a major contribution for production of hard x-ray photons
      in Damavand tokamak.

PMID- 24880372
TI  - Design of a fully-fiber multi-chord interferometer and a new phase-shift
      demodulation method for field-reversed configuration.
AB  - A 633 nm laser interferometer has been designed based on a novel concept, which,
      without the acousto-optic modulator or the demodulator circuit, adopts the fibers
      to connect all elements except photodetectors and oscilloscope in this system to
      make it more compact, portable, and efficient. The noteworthy feature is to
      mathematically compare the two divided interference signals, which have the same
      phase-shift caused by the electron density but possess the different initial
      phase and low angular frequencies. It is possible to read the plasma density
      directly on the oscilloscope by our original mathematic demodulation method
      without a camera. Based on the Abel inversion algorithm, the radial electron
      density profiles versus time can be obtained by using the multi-chord system. The
      designed measurable phase shift ranges from 0 to 2pi rad corresponding to the
      maximum line integral of electron density less than 3.5 * 10(17) cm(-2), and the
      phase accuracy is about 0.017 rad corresponding to the line integral of electron
      density accuracy of 1 * 10(15) cm(-2). After the construction of eight-chord
      interferometer, it will provide the detailed time resolved information of the
      spatial distribution of the electron density in the field-reversed configuration
      (FRC) plasma target produced by the "Yingguang-1" programmed-discharge device,
      which is being constructed in the Key Laboratory of Pulsed Power, China Academy
      of Engineering Physics. 

PMID- 24880374
TI  - A long-pulse repetitive operation magnetically insulated transmission line
      oscillator.
AB  - The improved magnetically insulated transmission line oscillator (MILO) is a
      gigawatt-class L-band high power microwave tube. It has allowed us to generate
      3.1 GW pulse of 40 ns duration in the single-pulse operation and 500 MW pulse of
      25 ns duration in the repetition rate operation. However, because of the severe
      impedance mismatch, the power conversion efficiency is only about 4% in the
      repetition rate operation. In order to eliminate the impedance mismatch and
      obtain repetitive long-pulse high-power microwave (HPM), a series of experiments
      are carried out and the recent progress is presented in this paper. In the single
      pulse operation, when the diode voltage is 466 kV and current is 41.6 kA, the
      radiated microwave power is above 2.2 GW, the pulse duration is above 102 ns, the
      microwave frequency is about 1.74 GHz, and the power conversion efficiency is
      about 11.5%. In the repetition rate operation, under the condition of the diode
      voltage about 400 kV, beam current about 38 kA, the radiated microwave power is
      about 1.0 GW, the pulse duration is about 85 ns. Moreover, the radiated microwave
      power and the pulse duration decline little by little when the shot numbers
      increase gradually. The experimental results show that the impedance matching is
      a vital factor for HPM systems and one of the major technical challenges is to
      improve the cathode for the repetition rate operation MILO. 

PMID- 24880373
TI  - High spatial resolution mapping of deposition layers on plasma facing materials
      by laser ablation microprobe time-of-flight mass spectroscopy.
AB  - A laser ablation microprobe time-of-flight mass spectroscopy (LAM-TOF-MS) system
      with high spatial resolution, ~20 nm in depth and ~500 MUm or better on the
      surface, is developed to analyze the composition distributions of deposition
      layers on the first wall materials or first mirrors in tokamak. The LAM-TOF-MS
      system consists of a laser ablation microprobe combined with a TOF-MS and a data
      acquisition system based on a LabVIEW program software package. Laser induced
      ablation combined with TOF-MS is an attractive method to analyze the depth
      profile of deposited layer with successive laser shots, therefore, it can provide
      information for composition reconstruction of the plasma wall interaction
      process. In this work, we demonstrate that the LAM-TOF-MS system is capable of
      characterizing the depth profile as well as mapping 2D composition of deposited
      film on the molybdenum first mirror retrieved from HL-2A tokamak, with particular
      emphasis on some of the species produced during the ablation process. The
      presented LAM-TOF-MS system provides not only the 3D characterization of
      deposition but also the removal efficiency of species of concern.

PMID- 24880375
TI  - Metal vapor target for precise studies of ion-atom collisions.
AB  - Although different ion-atom collisions have been studied in various contexts,
      precise values of cross-sections for many atomic processes were seldom obtained.
      One of the main uncertainties originates from the value of target densities. In
      this paper, we describe a unique method to measure a target density precisely
      with a combination of physical vapor deposition and inductively coupled plasma
      optical emission spectrometry. This method is preliminarily applied to a charge
      transfer cross-section measurement in collisions between highly charged ions and
      magnesium vapor. The final relative uncertainty of the target density is less
      than 2.5%. This enables the precise studies of atomic processes in ion-atom
      collisions, even though in the trial test the deduction of precise capture cross
      sections was limited by other systematic errors. 

PMID- 24880376
TI  - Data fusion in X-ray computed tomography using a superiorization approach.
AB  - X-ray computed tomography (CT) is an important and widespread inspection
      technique in industrial non-destructive testing. However, large-sized and heavily
      absorbing objects cause artifacts due to either the lack of penetration of the
      specimen in specific directions or by having data from only a limited angular
      range of views. In such cases, valuable information about the specimen is not
      revealed by the CT measurements alone. Further imaging modalities, such as
      optical scanning and ultrasonic testing, are able to provide data (such as an
      edge map) that are complementary to the CT acquisition. In this paper, a
      superiorization approach (a newly developed method for constrained optimization)
      is used to incorporate the complementary data into the CT reconstruction; this
      allows precise localization of edges that are not resolvable from the CT data by
      itself. Superiorization, as presented in this paper, exploits the fact that the
      simultaneous algebraic reconstruction technique (SART), often used for CT
      reconstruction, is resilient to perturbations; i.e., it can be modified to
      produce an output that is as consistent with the CT measurements as the output of
      unmodified SART, but is more consistent with the complementary data. The
      application of this superiorized SART method to measured data of a turbine blade
      demonstrates a clear improvement in the quality of the reconstructed image. 

PMID- 24880377
TI  - Monte Carlo model of a polychromatic laboratory based edge illumination x-ray
      phase contrast system.
AB  - A Monte Carlo model of a polychromatic laboratory based (coded aperture) edge
      illumination x-ray phase contrast imaging system has been developed and validated
      against experimental data. The ability for the simulation framework to be used to
      model two-dimensional images is also shown. The Monte Carlo model has been
      developed using the McXtrace engine and is polychromatic, i.e., results are
      obtained through the use of the full x-ray spectrum rather than an effective
      energy. This type of simulation can in future be used to model imaging of objects
      with complex geometry, for system prototyping, as well as providing a first step
      towards the development of a simulation for modelling dose delivery as a part of
      translating the imaging technique for use in clinical environments. 

PMID- 24880378
TI  - Ultrasound guided fluorescence molecular tomography with improved quantification
      by an attenuation compensated Born-normalization and in vivo preclinical study of
      cancer.
AB  - Ultrasound imaging, having the advantages of low-cost and non-invasiveness over
      MRI and X-ray CT, was reported by several studies as an adequate complement to
      fluorescence molecular tomography with the perspective of improving localization
      and quantification of fluorescent molecular targets in vivo. Based on the
      previous work, an improved dual-modality Fluorescence-Ultrasound imaging system
      was developed and then validated in imaging study with preclinical tumor model.
      Ultrasound imaging and a profilometer were used to obtain the anatomical prior
      information and 3D surface, separately, to precisely extract the tissue boundary
      on both sides of sample in order to achieve improved fluorescence reconstruction.
      Furthermore, a pattern-based fluorescence reconstruction on the detection side
      was incorporated to enable dimensional reduction of the dataset while keeping the
      useful information for reconstruction. Due to its putative role in the current
      imaging geometry and the chosen reconstruction technique, we developed an
      attenuation compensated Born-normalization method to reduce the attenuation
      effects and cancel off experimental factors when collecting quantitative
      fluorescence datasets over large area. Results of both simulation and phantom
      study demonstrated that fluorescent targets could be recovered accurately and
      quantitatively using this reconstruction mechanism. Finally, in vivo experiment
      confirms that the imaging system associated with the proposed image
      reconstruction approach was able to extract both functional and anatomical
      information, thereby improving quantification and localization of molecular
      targets. 

PMID- 24880379
TI  - Measurement of the index of refraction of MUm crystals by a confocal laser
      microscope--potential application for the refractive index mapping of MUm scale.
AB  - A conventional laser microscope can be used to derive the index of refractivity
      by the ratio of geometrical height of the transparent platelet to the apparent
      height of the normal incident light for very small crystals in the wide size
      range. We demonstrate that the simple method is effective for the samples from
      100 MUm to 16 MUm in size using alkali halide crystals as a model system. The
      method is also applied for the surface fractured micro-crystals and an inclined
      crystal with microscopic size regime. Furthermore, we present two-dimensional
      refractive index mapping as well as two-dimensional height profile for the
      mixture of three alkali halides, KCl, KI, and NaCl, all are MUm in size. 

PMID- 24880380
TI  - Field programmable gate array processing for an improved low-light-level imaging
      system with higher detection sensibility.
AB  - The method which employs the frame accumulation and shaped function is effective
      in low-light-level imaging. However, it has drawbacks of lower imaging speed and
      complex operation. To optimize the method, we provide the design of an improved
      low-light-level imaging system with higher detection sensibility. The design is
      developed specifically for a faster imaging speed based on field programmable
      gate arrays. It features the use of least-square algorithm and a saw-tooth wave
      varied light applied to the image sensor. By manipulation of the video signal in
      synchronous dynamic random access memory, a low-light-level image which was
      previously undetectable can be estimated. The design simplifies the imaging
      process and doubles the imaging speed, and makes the system adapted to long range
      imaging. 

PMID- 24880381
TI  - Magnetoelectric force microscopy based on magnetic force microscopy with
      modulated electric field.
AB  - We present the realization of a mesoscopic imaging technique, namely, the
      Magnetoelectric Force Microscopy (MeFM), for visualization of local
      magnetoelectric effect. The basic principle of MeFM is the lock-in detection of
      local magnetoelectric response, i.e., the electric field-induced magnetization,
      using magnetic force microscopy. We demonstrate MeFM capability by visualizing
      magnetoelectric domains on single crystals of multiferroic hexagonal manganites.
      Results of several control experiments exclude artifacts or extrinsic origins of
      the MeFM signal. The parameters are tuned to optimize the signal to noise ratio. 

PMID- 24880382
TI  - Experimental cell for molecular beam deposition and magnetic resonance studies of
      matrix isolated radicals at temperatures below 1 K.
AB  - We present the design and performance of an experimental cell constructed for
      matrix isolation studies of H and D atoms in solid H2/D2 films, which are created
      by molecular beam deposition at temperatures below 1 K. The sample cell allows
      sensitive weighing of the films by a quartz microbalance (QM) and their studies
      by magnetic resonance techniques in a strong magnetic field of 4.6 T. We are able
      to regulate the deposition rate in the range from 0.01 to 10 molecular layers/s,
      and measure the thickness with ~0.2 monolayer resolution. The upper QM electrode
      serves as a mirror for a 128 GHz Fabry-Perot resonator connected to an electron
      spin resonance (ESR) spectrometer. H and D atoms were created by RF discharge in
      situ in the sample cell, and characterized by ESR and electron-nuclear double
      resonance. From the magnetic resonance measurements we conclude that the films
      are smooth and provide homogeneous trapping conditions for embedded atoms. The
      current sample cell design also makes it possible to calibrate the ESR signal and
      estimate the average and local concentrations of H and D radicals in the film. 

PMID- 24880383
TI  - Specific heat measurement set-up for quench condensed thin superconducting films.
AB  - We present a set-up designed for the measurement of specific heat of very thin or
      ultra-thin quench condensed superconducting films. In an ultra-high vacuum
      chamber, materials of interest can be thermally evaporated directly on a silicon
      membrane regulated in temperature from 1.4 K to 10 K. On this membrane, a heater
      and a thermometer are lithographically fabricated, allowing the measurement of
      heat capacity of the quench condensed layers. This apparatus permits the
      simultaneous thermal and electrical characterization of successively deposited
      layers in situ without exposing the deposited materials to room temperature or
      atmospheric conditions, both being irreversibly harmful to the samples. This
      system can be used to study specific heat signatures of phase transitions through
      the superconductor to insulator transition of quench condensed films. 

PMID- 24880384
TI  - Vectorial Kerr magnetometer for simultaneous and quantitative measurements of the
      in-plane magnetization components.
AB  - A vectorial magneto-optic Kerr effect (v-MOKE) setup with simultaneous and
      quantitative determination of the two in-plane magnetization components is
      described. The setup provides both polarization rotations and reflectivity
      changes at the same time for a given sample orientation with respect to a
      variable external magnetic field, as well as allowing full angular studies. A
      classical description based on the Jones formalism is used to calculate the
      setup's properties. The use of different incoming light polarizations and/or MOKE
      geometries, as well as the errors due to misalignment and solutions are
      discussed. To illustrate the capabilities of the setup a detailed study of a
      model four-fold anisotropy system is presented. Among others, the setup allows to
      study the angular dependence of the hysteresis phenomena, remanences, critical
      fields, and magnetization reversal processes, as well as the accurate
      determination of the easy and hard magnetization directions, domain wall
      orientations, and magnetic anisotropies. 

PMID- 24880385
TI  - A 31 T split-pair pulsed magnet for single crystal x-ray diffraction at low
      temperature.
AB  - We have developed a pulsed magnet system with panoramic access for synchrotron x
      ray diffraction in magnetic fields up to 31 T and at low temperature down to 1.5
      K. The apparatus consists of a split-pair magnet, a liquid nitrogen bath to cool
      the pulsed coil, and a helium cryostat allowing sample temperatures from 1.5 up
      to 250 K. Using a 1.15 MJ mobile generator, magnetic field pulses of 60 ms length
      were generated in the magnet, with a rise time of 16.5 ms and a repetition rate
      of 2 pulses/h at 31 T. The setup was validated for single crystal diffraction on
      the ESRF beamline ID06.

PMID- 24880386
TI  - Continuous flow, explosives vapor generator and sensor chamber.
AB  - A novel liquid injection vapor generator (LIVG) is demonstrated that is amenable
      to low vapor pressure explosives, 2,4,6-trinitrotoluene and hexahydro-1,3,5
      trinitro-1,3,5-triazine. The LIVG operates in a continuous manner, providing a
      constant and stable vapor output over a period of days and whose concentration
      can be extended over as much as three orders of magnitude. In addition, a large
      test atmosphere chamber attached to the LIVG is described, which enables the
      generation of a stable test atmosphere with controllable humidity and
      temperature. The size of the chamber allows for the complete insertion of testing
      instruments or arrays of materials into a uniform test atmosphere, and various
      electrical feedthroughs, insertion ports, and sealed doors permit simple and
      effective access to the sample chamber and its vapor. 

PMID- 24880387
TI  - The SupraThermal Ion Monitor for space weather predictions.
AB  - Measurement of suprathermal energy ions in the heliosphere has always been
      challenging because (1) these ions are situated in the energy regime only a few
      times higher than the solar wind plasma, where intensities are orders of
      magnitude higher and (2) ion energies are below or close to the threshold of
      state-of-art solid-state detectors. Suprathermal ions accelerated at coronal mass
      ejection-driven shocks propagate out ahead of the shocks. These shocks can cause
      geomagnetic storms in the Earth's magnetosphere that can affect spacecraft and
      ground-based power and communication systems. An instrument with sufficient
      sensitivity to measure these ions can be used to predict the arrival of the
      shocks and provide an advance warning for potentially geo-effective space
      weather. In this paper, we present a novel energy analyzer concept, the
      Suprathermal Ion Monitor (STIM) that is designed to measure suprathermal ions
      with high sensitivity. We show results from a laboratory prototype and
      demonstrate the feasibility of the concept. A list of key performances is given,
      as well as a discussion of various possible detectors at the back end. STIM is an
      ideal candidate for a future space weather monitor in orbit upstream of the near
      earth environment, for example, around L1. A scaled-down version is suitable for
      a CubeSat mission. Such a platform allows proofing the concept and demonstrating
      its performance in the space environment. 

PMID- 24880389
TI  - Control of critical coupling in a coiled coaxial cable resonator.
AB  - This paper reports a coiled coaxial cable resonator fabricated by cutting a slot
      in a spring-like coiled coaxial cable to produce a periodic perturbation.
      Electromagnetic coupling between two neighboring slots was observed. By
      manipulating the number of slots, critical coupling of the coiled coaxial cable
      resonator can be well controlled. An ultrahigh signal-to-noise ratio (over 50 dB)
      at the resonant frequency band was experimentally achieved from a coiled coaxial
      cable resonator with 38 turns. A theoretic model is developed to understand the
      device physics. The proposed device can be potentially used as a high quality and
      flexibly designed band-stop filter or a sensor in structural health monitoring. 

PMID- 24880388
TI  - A high precision, compact electromechanical ground rotation sensor.
AB  - We present a mechanical rotation sensor consisting of a balance pivoting on a
      tungsten carbide knife edge. These sensors are important for precision seismic
      isolation systems, as employed in land-based gravitational wave interferometers
      and for the new field of rotational seismology. The position sensor used is an
      air-core linear variable differential transformer with a demonstrated noise floor
      of 1 * 10-11 m/?Hz. We describe the instrument construction and demonstrate low
      noise operation with a noise floor upper bound of 5.7 * 10-9 rad/?Hz at 10 mHz
      and 6.4 * 10-10 rad/?Hz at 0.1 Hz. The performance of the knife edge hinge is
      compatible with a behaviorur free of noise from dislocation self-organized
      criticality.

PMID- 24880390
TI  - A compact, multichannel, and low noise arbitrary waveform generator.
AB  - A new type of high functionality, fast, compact, and easy programmable arbitrary
      waveform generator for low noise physical measurements is presented. The
      generator provides 7 fast differential waveform channels with a maximum bandwidth
      up to 200 MHz frequency. There are 6 fast pulse generators on the generator board
      with 78 ps time resolution in both duration and delay, 3 of them with amplitude
      control. The arbitrary waveform generator is additionally equipped with two
      auxiliary slow 16 bit analog-to-digital converters and four 16 bit digital-to
      analog converters for low frequency applications. Electromagnetic shields are
      introduced to the power supply, digital, and analog compartments and with a
      proper filter design perform more than 110 dB digital noise isolation to the
      output signals. All the output channels of the board have 50 Omega SubMiniature
      version A termination. The generator board is suitable for use as a part of a
      high sensitive physical equipment, e.g., fast read out and manipulation of
      nuclear magnetic resonance or superconducting quantum systems and any other
      application, which requires electromagnetic interference free fast pulse and
      arbitrary waveform generation. 

PMID- 24880391
TI  - Atmospheric pressure plasma jet with high-voltage power supply based on
      piezoelectric transformer.
AB  - The dielectric barrier discharge plasma jet, an example of the nonthermal
      atmospheric pressure plasma jet (APPJ), generates low-temperature plasmas that
      are suitable for the atomization of volatile species and can also be served as an
      ionization source for ambient mass and ion mobility spectrometry. A new design of
      APPJ for mass spectrometry has been built in our group. In these plasma sources
      magnetic transformers (MTs) and inductors are typically used in power supplies
      but they present several drawbacks that are even more evident when dealing with
      high-voltage normally used in APPJs. To overcome these disadvantages, high
      frequency generators with the absence of MT are proposed in the literature.
      However, in the case of miniaturized APPJs these conventional power converters,
      built of ferromagnetic cores and inductors or by means of LC resonant tank
      circuits, are not so useful as piezoelectric transformer (PT) based power
      converters due to bulky components and small efficiency. We made and examined a
      novel atmospheric pressure plasma jet with PT supplier served as ionization
      source for ambient mass spectrometry, and especially mobile spectrometry where
      miniaturization, integration of components, and clean plasma are required. The
      objective of this paper is to describe the concept, design, and implementation of
      this miniaturized piezoelectric transformer-based atmospheric pressure plasma
      jet. 

PMID- 24880392
TI  - Cross-correlation measurement of quantum shot noise using homemade transimpedance
      amplifiers.
AB  - We report a cross-correlation measurement system, based on a new approach, which
      can be used to measure shot noise in a mesoscopic conductor at milliKelvin
      temperatures. In contrast to other measurement systems in which high-speed low
      noise voltage amplifiers are commonly used, our system employs homemade
      transimpedance amplifiers (TAs). The low input impedance of the TAs significantly
      reduces the crosstalk caused by unavoidable parasitic capacitance between wires.
      The TAs are designed to have a flat gain over a frequency band from 2 kHz to 1
      MHz. Low-noise performance is attained by installing the TAs at a 4 K stage of a
      dilution refrigerator. Our system thus fulfills the technical requirements for
      cross-correlation measurements: low noise floor, high frequency band, and
      negligible crosstalk between two signal lines. Using our system, shot noise
      generated at a quantum point contact embedded in a quantum Hall system is
      measured. The good agreement between the obtained shot-noise data and theoretical
      predictions demonstrates the accuracy of the measurements. 

PMID- 24880393
TI  - An induction method to calculate the complex permeability of soft magnetic films
      without a reference sample.
AB  - A new analytical method has been proposed by utilizing an electromagnetic
      induction principle with a short-circuited microstrip line jig and the complex
      permeability spectra can be calculated without a known reference sample. The new
      method using the short-circuited microstrip line can exhibit higher sensitivity
      and a wider frequency band than coplanar waveguide and pick-up coil. Two magnetic
      thin films having a good in-plane uniaxial anisotropy are measured by using the
      induction method. The results show typical complex permeability spectra in good
      agreement with the theoretical analytical results. The measured permeability
      values are verified by comparing with the initial susceptibility derived from the
      sweeping field results. The difference of measured permeability values is less
      than 5%. 

PMID- 24880394
TI  - Bias-field controlled phasing and power combination of gyromagnetic nonlinear
      transmission lines.
AB  - Gyromagnetic Nonlinear Transmission Lines (NLTLs) generate microwaves through the
      damped gyromagnetic precession of the magnetic moments in ferrimagnetic material,
      and are thus utilized as compact, solid-state, frequency agile, high power
      microwave (HPM) sources. The output frequency of a NLTL can be adjusted by
      control of the externally applied bias field and incident voltage pulse without
      physical alteration to the structure of the device. This property provides a
      frequency tuning capability not seen in many conventional e-beam based HPM
      sources. The NLTLs developed and tested are mesoband sources capable of
      generating MW power levels in the L, S, and C bands of the microwave spectrum.
      For an individual NLTL the output power at a given frequency is determined by
      several factors including the intrinsic properties of the ferrimagnetic material
      and the transmission line structure. Hence, if higher power levels are to be
      achieved, it is necessary to combine the outputs of multiple NLTLs. This can be
      accomplished in free space using antennas or in a transmission line via a power
      combiner. Using a bias-field controlled delay, a transient, high voltage,
      coaxial, three port, power combiner was designed and tested. Experimental results
      are compared with the results of a transient COMSOL simulation to evaluate
      combiner performance. 

PMID- 24880395
TI  - Investigation and optimization of low-frequency noise performance in readout
      electronics of dc superconducting quantum interference device.
AB  - We investigated and optimized the low-frequency noise characteristics of a
      preamplifier used for readout of direct current superconducting quantum
      interference devices (SQUIDs). When the SQUID output was detected directly using
      a room-temperature low-voltage-noise preamplifier, the low-frequency noise of a
      SQUID system was found to be dominated by the input current noise of the
      preamplifiers in case of a large dynamic resistance of the SQUID. To reduce the
      current noise of the preamplifier in the low-frequency range, we investigated the
      dependence of total preamplifier noise on the collector current and source
      resistance. When the collector current was decreased from 8.4 mA to 3 mA in the
      preamplifier made of 3 parallel SSM2220 transistor pairs, the low-frequency total
      voltage noise of the preamplifier (at 0.1 Hz) decreased by about 3 times for a
      source resistance of 30 Omega whereas the white noise level remained nearly
      unchanged. Since the relative contribution of preamplifier's input voltage and
      current noise is different depending on the dynamic resistance or flux-to-voltage
      transfer of the SQUID, the results showed that the total noise of a SQUID system
      at low-frequency range can be improved significantly by optimizing the
      preamplifier circuit parameters, mainly the collector current in case of low
      noise bipolar transistor pairs. 

PMID- 24880396
TI  - Applying of microwave asymmetrical double-ridged waveguide for measuring of the
      integrated optical electrodeless electric field sensor sensitivity.
AB  - We present a new method for investigation of sensitivity of the integrated
      optical electrodeless electric field sensor. This method is based on a compact
      microwave asymmetrical double-ridged waveguide with regular inhomogeneities.
      Small dimensions of the waveguide along with medium power of the microwave
      generator produce a strong electric field. The efficiency of the presented
      experimental unit was verified in the course of testing of the real integrated
      optical electrodeless electric field sensor (E-sensor). 

PMID- 24880397
TI  - High-precision thermal and electrical characterization of thermoelectric modules.
AB  - This paper describes an apparatus for performing high-precision electrical and
      thermal characterization of thermoelectric modules (TEMs). The apparatus is
      calibrated for operation between 20  degrees C and 80  degrees C and is normally
      used for measurements of heat currents in the range 0-10 W. Precision thermometry
      based on miniature thermistor probes enables an absolute temperature accuracy of
      better than 0.010  degrees C. The use of vacuum isolation, thermal guarding, and
      radiation shielding, augmented by a careful accounting of stray heat leaks and
      uncertainties, allows the heat current through the TEM under test to be
      determined with a precision of a few mW. The fractional precision of all measured
      parameters is approximately 0.1%.

PMID- 24880398
TI  - Calibration of a thin metal foil for infrared imaging video bolometer to estimate
      the spatial variation of thermal diffusivity using a photo-thermal technique.
AB  - A thin metal foil is used as a broad band radiation absorber for the InfraRed
      imaging Video Bolometer (IRVB), which is a vital diagnostic for studying three
      dimensional radiation structures from high temperature plasmas in the Large
      Helical Device. The two-dimensional (2D) heat diffusion equation of the foil
      needs to be solved numerically to estimate the radiation falling on the foil
      through a pinhole geometry. The thermal, physical, and optical properties of the
      metal foil are among the inputs to the code besides the spatiotemporal variation
      of temperature, for reliable estimation of the exhaust power from the plasma
      illuminating the foil. The foil being very thin and of considerable size, non
      uniformities in these properties need to be determined by suitable calibration
      procedures. The graphite spray used for increasing the surface emissivity also
      contributes to a change in the thermal properties. This paper discusses the
      application of the thermographic technique for determining the spatial variation
      of the effective in-plane thermal diffusivity of the thin metal foil and graphite
      composite. The paper also discusses the advantages of this technique in the light
      of limitations and drawbacks presented by other calibration techniques being
      practiced currently. The technique is initially applied to a material of known
      thickness and thermal properties for validation and finally to thin foils of gold
      and platinum both with two different thicknesses. It is observed that the effect
      of the graphite layer on the estimation of the thermal diffusivity becomes more
      pronounced for thinner foils and the measured values are approximately 2.5-3
      times lower than the literature values. It is also observed that the percentage
      reduction in thermal diffusivity due to the coating is lower for high thermal
      diffusivity materials such as gold. This fact may also explain, albeit partially,
      the higher sensitivity of the platinum foil as compared to gold. 

PMID- 24880399
TI  - New contactless method for thermal diffusivity measurements using modulated
      photothermal radiometry.
AB  - Modulated photothermal radiometry is a non-destructive and contactless technique
      for the characterization of materials. It has two major advantages: a good signal
      to-noise ratio through a synchronous detection and a low dependence on the
      heating power and the optical properties of the sample surface. This paper
      presents a new method for characterizing the thermal diffusivity of a material
      when the phase shift between a modulated laser power signal and the thermal
      signal of a plate sample is known at different frequencies. The method is based
      on a three-dimensional analytical model which is used to determine the
      temperature amplitude and the phase in the laser heating of the plate. A new
      simple formula was developed through multi-parametric analysis to determine the
      thermal diffusivity of the plate with knowledge of the frequency at the minimum
      phase shift, the laser beam radius r0 and the sample thickness L. This method was
      developed to control the variation of the thermal diffusivity of nuclear
      components and it was first applied to determine the thermal diffusivity of
      different metals: 304 L stainless steel, nickel, titanium, tungsten, molybdenum,
      zinc, and iron. The experimental results were obtained with 5%-10% accuracy and
      corresponded well with the reference values. The present paper also demonstrates
      the limit of application of this method for plate with thickness r0/100 <= L <=
      r0/2. The technique is deemed interesting for the characterization of barely
      accessible components that require a contactless measurement. 

PMID- 24880400
TI  - Fast Seebeck coefficient measurement based on dynamic method.
AB  - A setup based on dynamic method was developed for fast Seebeck coefficient
      measurement from room temperature to 473 K. Two T-type thermocouples with a
      response time of less than 0.1 s were used to measure the dynamic temperatures of
      the sample. The Cu wires of the two thermocouples served as leads for Seebeck
      voltage measurement. The dynamic temperature feature of the setup was
      characterized. Test measurements were conducted with LaCo(0.9)Cu(0.1)O3 and
      LaCo(0.8)5Cu(0.15)O3 samples with the customized setup, and the results had a
      difference of +/-8.4% compared with the data provided by ZEM-2 (Ulvac-Riko,
      Japan), which showed that the Seebeck measurement with the customized setup was
      reliable. In addition, the error on the Seebeck coefficient caused by the dynamic
      variation of temperature was discussed. The setup described in this paper has the
      advantage of fast Seebeck coefficient measurement with a measurement speed of
      about 14-23 K min(-1).

PMID- 24880401
TI  - Measurement of total ultrasonic power using thermal expansion and change in
      buoyancy of an absorbing target.
AB  - The Radiation Force Balance (RFB) technique is well established and most widely
      used for the measurement of total ultrasonic power radiated by ultrasonic
      transducer. The technique is used as a primary standard for calibration of
      ultrasonic transducers with relatively fair uncertainty in the low power (below 1
      W) regime. In this technique, uncertainty comparatively increases in the range of
      few watts wherein the effects such as thermal heating of the target, cavitations,
      and acoustic streaming dominate. In addition, error in the measurement of
      ultrasonic power is also caused due to movement of absorber at relatively high
      radiated force which occurs at high power level. In this article a new technique
      is proposed which does not measure the balance output during transducer energized
      state as done in RFB. It utilizes the change in buoyancy of the absorbing target
      due to local thermal heating. The linear thermal expansion of the target changes
      the apparent mass in water due to buoyancy change. This forms the basis for the
      measurement of ultrasonic power particularly in watts range. The proposed method
      comparatively reduces uncertainty caused by various ultrasonic effects that occur
      at high power such as overshoot due to momentum of target at higher radiated
      force. The functionality of the technique has been tested and compared with the
      existing internationally recommended RFB technique. 

PMID- 24880402
TI  - Resonant frequency detection and adjustment method for a capacitive transducer
      with differential transformer bridge.
AB  - The capacitive transducer with differential transformer bridge is widely used in
      ultra-sensitive space accelerometers due to their simple structure and high
      resolution. In this paper, the front-end electronics of an inductive-capacitive
      resonant bridge transducer is analyzed. The analysis result shows that the
      performance of this transducer depends upon the case that the AC pumping
      frequency operates at the resonance point of the inductive-capacitive bridge. The
      effect of possible mismatch between the AC pumping frequency and the actual
      resonant frequency is discussed, and the theoretical analysis indicates that the
      output voltage noise of the front-end electronics will deteriorate by a factor of
      about 3 due to either a 5% variation of the AC pumping frequency or a 10%
      variation of the tuning capacitance. A pre-scanning method to determine the
      actual resonant frequency is proposed followed by the adjustment of the operating
      frequency or the change of the tuning capacitance in order to maintain expected
      high resolution level. An experiment to verify the mismatching effect and the
      adjustment method is provided. 

PMID- 24880403
TI  - Improving environmental noise suppression for micronewton force sensing based on
      electrostatic by injecting air damping.
AB  - A micro/nano force can be traced to the International System of Units by means of
      an electrostatic force balance weight system. However, the micro/nano force
      measurement system is susceptible to environmental disturbances. Various methods
      have been proposed to reduce the effect of environmental disturbances and obtain
      high resolution and fast response. In this paper, we introduce a combination of
      air damping and inherent damping from the internal molecular friction of spring
      suspension. This will optimize system stability and improve environmental noise
      suppression. Results from the air damping model show that the damping ratio
      increases from 0.0005 to 0.1, which improves the vibration resistance. We found
      that the system with air damping has the advantages of fast response and low
      scatter. 

PMID- 24880405
TI  - Electronic nose with a new feature reduction method and a multi-linear classifier
      for Chinese liquor classification.
AB  - An electronic nose (e-nose) was designed to classify Chinese liquors of the same
      aroma style. A new method of feature reduction which combined feature selection
      with feature extraction was proposed. Feature selection method used 8 feature
      selection algorithms based on information theory and reduced the dimension of the
      feature space to 41. Kernel entropy component analysis was introduced into the e
      nose system as a feature extraction method and the dimension of feature space was
      reduced to 12. Classification of Chinese liquors was performed by using back
      propagation artificial neural network (BP-ANN), linear discrimination analysis
      (LDA), and a multi-linear classifier. The classification rate of the multi-linear
      classifier was 97.22%, which was higher than LDA and BP-ANN. Finally the
      classification of Chinese liquors according to their raw materials and
      geographical origins was performed using the proposed multi-linear classifier and
      classification rate was 98.75% and 100%, respectively. 

PMID- 24880404
TI  - A portable time-domain LED fluorimeter for nanosecond fluorescence lifetime
      measurements.
AB  - Fluorescence lifetime measurements are becoming increasingly important in
      chemical and biological research. Time-domain lifetime measurements offer
      fluorescence multiplexing and improved handling of interferers compared with the
      frequency-domain technique. In this paper, an all solid-state, filterless, and
      highly portable light-emitting-diode based time-domain fluorimeter (LED TDF) is
      reported for the measurement of nanosecond fluorescence lifetimes. LED based
      excitation provides more wavelengths options compared to laser diode based
      excitation, but the excitation is less effective due to the uncollimated beam,
      less optical power, and longer latency in state transition. Pulse triggering and
      pre-bias techniques were implemented in our LED TDF to improve the peak optical
      power to over 100 mW. The proposed pulsing circuit achieved an excitation light
      fall time of less than 2 ns. Electrical resetting technique realized a time-gated
      photo-detector to remove the interference of the excitation light with
      fluorescence. These techniques allow the LED fluorimeter to accurately measure
      the fluorescence lifetime of fluorescein down to concentration of 0.5 MUM. In
      addition, all filters required in traditional instruments are eliminated for the
      non-attenuated excitation/emission light power. These achievements make the
      reported device attractive to biochemical laboratories seeking for highly
      portable lifetime detection devices for developing sensors based on fluorescence
      lifetime changes. The device was initially validated by measuring the lifetimes
      of three commercial fluorophores and comparing them with reported lifetime data.
      It was subsequently used to characterize a ZnSe quantum dot based DNA sensor. 

PMID- 24880406
TI  - A self-reconfiguring metamorphic nanoinjector for injection into mouse zygotes.
AB  - This paper presents a surface-micromachined microelectromechanical system
      nanoinjector designed to inject DNA into mouse zygotes which are ~90 MUm in
      diameter. The proposed injection method requires that an electrically charged,
      DNA coated lance be inserted into the mouse zygote. The nanoinjector's principal
      design requirements are (1) it must penetrate the lance into the mouse zygote
      without tearing the cell membranes and (2) maintain electrical connectivity
      between the lance and a stationary bond pad. These requirements are satisfied
      through a two-phase, self-reconfiguring metamorphic mechanism. In the first
      motion subphase a change-point six-bar mechanism elevates the lance to ~45 MUm
      above the substrate. In the second motion subphase, a compliant folded-beam
      suspension allows the lance to translate in-plane at a constant height as it
      penetrates the cell membranes. The viability of embryos following nanoinjection
      is presented as a metric for quantifying how well the nanoinjector mechanism
      fulfills its design requirements of penetrating the zygote without causing
      membrane damage. Viability studies of nearly 3000 nanoinjections resulted in
      71.9% of nanoinjected zygotes progressing to the two-cell stage compared to 79.6%
      of untreated embryos.

PMID- 24880407
TI  - Apparatus to characterize gas sensor response under real-world conditions in the
      lab.
AB  - The use of semiconducting metal-oxide (MOX) based gas sensors in demanding
      applications such as climate and environmental research as well as industrial
      applications is currently hindered by their poor reproducibility, selectivity,
      and sensitivity. This is mainly due to the sensing mechanism which relies on the
      change of conductivity of the metal-oxide layer. To be of use for advanced
      applications metal-oxide (MOX) gas sensors need to be carefully prepared and
      characterized in laboratory environments prior to deployment. This paper
      describes the working principle, design, and use of a new apparatus that can
      emulate real-world conditions in the laboratory and characterize the MOX gas
      sensor signal in tailor-made atmospheres. In particular, this includes the
      control of trace gas concentrations and the control of oxygen and humidity levels
      which are important for the surface chemistry of metal-oxide based sensors.
      Furthermore, the sensor temperature can be precisely controlled, which is a key
      parameter of semiconducting, sensitive layers, and their response to particular
      gas compositions. The setup also allows to determine the power consumption of
      each device individually which may be used for performance benchmarking or
      monitoring changes of the temperature of the gas composition. Both, the working
      principle and the capabilities of the gas measurement chamber are presented in
      this paper employing tin dioxide (SnO2) based micro sensors as exemplary devices.

PMID- 24880408
TI  - Improving the accuracy of walking piezo motors.
AB  - Many application areas require ultraprecise, stiff, and compact actuator systems
      with a high positioning resolution in combination with a large range as well as a
      high holding and pushing force. One promising solution to meet these conflicting
      requirements is a walking piezo motor that works with two pairs of piezo elements
      such that the movement is taken over by one pair, once the other pair reaches its
      maximum travel distance. A resolution in the pm-range can be achieved, if
      operating the motor within the travel range of one piezo pair. However, applying
      the typical walking drive signals, we measure jumps in the displacement up to 2.4
      MUm, when the movement is given over from one piezo pair to the other. We analyze
      the reason for these large jumps and propose improved drive signals. The
      implementation of our new drive signals reduces the jumps to less than 42 nm and
      makes the motor ideally suitable to operate as a coarse approach motor in an
      ultra-high vacuum scanning tunneling microscope. The rigidity of the motor is
      reflected in its high pushing force of 6.4 N. 

PMID- 24880409
TI  - Low temperature and high magnetic field spectroscopic ellipsometry system.
AB  - We report on the design and implementation of a spectral ellipsometer at near
      infrared wavelength (700-1000 nm) for samples placed in high magnetic fields (up
      to 14 T) at low temperatures (~4.2 K). The main optical components are integrated
      in a probe, which can be inserted into a conventional long-neck He dewar and has
      a very long free-space optical path (~1.8 m*2). A polarizer-sample-(quarter-wave
      plate)-rotating analyzer configuration was employed. Two dielectric mirrors, one
      before and one after the sample in the optical path, helped to reflect the light
      back to the analyzer and a two-axis piezo-driven goniometer under the sample
      holder was used to control the direction of the reflected light. Functional test
      results performed on an intrinsic GaAs wafer and analysis on the random error of
      the system are shown. We obtained both amplitude and phase ellipsometric spectra
      simultaneously and observed helicity transformation at energies near the GaAs
      exciton transitions in the phase spectra. Significant shifts of them induced by
      magnetic fields were observed and fitted with a simple model. This system will
      allow us to study the collective magneto-optical response of materials and
      spatial dispersive exciton-polariton related problems in high external magnetic
      fields at low temperatures.

PMID- 24880410
TI  - Development of a 33 kV, 20 A long pulse converter modulator for high average
      power klystron.
AB  - Research, design, and development of high average power, long pulse modulators
      for the proposed Indian Spallation Neutron Source are underway at Raja Ramanna
      Centre for Advanced Technology. With this objective, a prototype of long pulse
      modulator capable of delivering 33 kV, 20 A at 5 Hz repetition rate has been
      designed and developed. Three Insulated Gate Bipolar Transistors (IGBT) based
      switching modules driving high frequency, high voltage transformers have been
      used to generate high voltage output. The IGBT based switching modules are
      shifted in phase by 120 degrees  with respect to each other. The switching
      frequency is 25 kHz. Pulses of 1.6 ms pulse width, 80 MUs rise time, and 70 MUs
      fall time have been achieved at the modulator output. A droop of +/-0.6% is
      achieved using a simple segmented digital droop correction technique. The total
      fault energy transferred to the load during fault has been measured by conducting
      wire burn tests and is found to be within 3.5 J. 

PMID- 24880412
TI  - Combined UHV/high-pressure catalysis setup for depth-resolved near-surface
      spectroscopic characterization and catalytic testing of model catalysts.
AB  - An ultra-high vacuum (UHV) setup for "real" and "inverse" model catalyst
      preparation, depth-resolved near-surface spectroscopic characterization, and
      quantification of catalytic activity and selectivity under technologically
      relevant conditions is described. Due to the all-quartz reactor attached directly
      to the UHV-chamber, transfer of the catalyst for in situ testing without
      intermediate contact to the ambient is possible. The design of the UHV-compatible
      re-circulating batch reactor setup allows the study of reaction kinetics under
      close to technically relevant catalytic conditions up to 1273 K without contact
      to metallic surfaces except those of the catalyst itself. With the attached
      differentially pumped exchangeable evaporators and the quartz-microbalance
      thickness monitoring equipment, a reproducible, versatile, and standardised
      sample preparation is possible. For three-dimensional near-surface sample
      characterization, the system is equipped with a hemispherical analyser for X-ray
      photoelectron spectroscopy (XPS), electron-beam or X-ray-excited Auger-electron
      spectroscopy, and low-energy ion scattering measurements. Due the dedicated
      geometry of the X-ray gun (54.7 degrees , "magic angle") and the rotatable sample
      holder, depth analysis by angle-resolved XPS measurements can be performed. Thus,
      by the combination of characterisation methods with different information depths,
      a detailed three-dimensional picture of the electronic and geometric structure of
      the model catalyst can be obtained. To demonstrate the capability of the
      described system, comparative results for depth-resolved sample characterization
      and catalytic testing in methanol steam reforming on PdGa and PdZn near-surface
      intermetallic phases are shown. 

PMID- 24880411
TI  - Four-point probe electrical resistivity scanning system for large area
      conductivity and activation energy mapping.
AB  - The electrical properties of metal oxides play a crucial role in the development
      of new photovoltaic (PV) systems. Here we demonstrate a general approach for the
      determination and analysis of these properties in thin films of new metal oxide
      based PV materials. A high throughput electrical scanning system, which
      facilitates temperature dependent measurements at different atmospheres for
      highly resistive samples, was designed and constructed. The instrument is capable
      of determining conductivity and activation energy values for relatively large
      sample areas, of about 72 * 72 mm(2), with the implementation of geometrical
      correction factors. The efficiency of our scanning system was tested using two
      different samples of CuO and commercially available Fluorine doped tin oxide
      coated glass substrates. Our high throughput tool was able to identify the
      electrical properties of both resistive metal oxide thin film samples with high
      precision and accuracy. The scanning system enabled us to gain insight into
      transport mechanisms with novel compositions and to use those insights to make
      smart choices when choosing materials for our multilayer thin film all oxide
      photovoltaic cells. 

PMID- 24880414
TI  - Fretting fatigue mechanism of bearing cap bolted joints.
AB  - Fretting fatigue is a common type of failure of the bearing cap bolted joints.
      This paper proposes a methodology to analyze the fretting fatigue mechanism of
      the bearing cap bolted joint. A biaxially loading system was designed to simulate
      fretting fatigue failure under typical engine working condition. Meanwhile, a
      submodel was developed in the finite element calculation to analyze the contact
      status and stress distribution of the structural models. The test result shows
      that long inclined cracks (about 650 MUm long, orientation at 17 degrees -34
      degrees ) initiate at the middle region of the contact interface. As the increase
      of the bolt pretension load (from 6000 N to 10,000 N), the crack initial location
      is getting away from the bolt screw, and the fretting fatigue lives is increasing
      (from 7.8 * 10(5) to 6.0 * 10(6)). With the fatigue phenomenon and the stress
      field analysis result, it concludes that the crack initiation is governed by the
      maximum shear stress; the bolt pretension load and the additional rotate torque
      caused by the bearing load are the two main factors which affect the fretting
      fatigue mechanism of the bearing cap bolted joints. It is beneficial to fretting
      fatigue lives of the bearing cap joints by increasing the bolt pretension load
      and restraining the oscillation of the bearing cap.

PMID- 24880413
TI  - An automated pipette puller for fabrication of glass micropipettes.
AB  - Glass micropipettes are versatile probing tools for performing micro- and nano
      manipulation tasks. This paper presents the design and development of an
      automated pipette puller system for fabrication of glass micropipettes. The
      pipette puller employs a new strategy for fabrication of micropipettes that
      enables achieving independent control of their taper, tip diameter, and bend
      angle, and also facilitates theoretical derivation of simple, approximate
      relationships between the pipette shape and the pulling parameters. Subsequently,
      the design and fabrication of the pipette puller is described, which include that
      of the pipette heating system, the mechanical motion stages, and the control
      electronics of the pipette puller. The fabricated pipette puller is
      experimentally evaluated to demonstrate control of the taper, tip diameter, and
      the bend-angle of the micropipette. Further, the dependence of the taper and tip
      diameter on the pulling parameters is evaluated and is shown to be in alignment
      with the proposed theoretical relationships. 

PMID- 24880415
TI  - Contactless automated manipulation of mesoscale objects using opto-fluidic
      actuation and visual servoing.
AB  - This work describes an automated opto-fluidic system for parallel non-contact
      manipulation of microcomponents. The strong dynamics of laser-driven
      thermocapillary flows were used to drag microcomponents at high speeds. High
      speed flows allowed to manipulate micro-objects in a parallel manner only using a
      single laser and a mirror scanner. An automated process was implemented using
      visual servoing with a high-speed camera in order to achieve accurately parallel
      manipulation. Automated manipulation of two glass beads of 30 up to 300 MUm in
      diameter moving in parallel at speeds in the range of mm/s was demonstrated.

PMID- 24880416
TI  - A second-generation constrained reaction volume shock tube.
AB  - We have developed a shock tube that features a sliding gate valve in order to
      mechanically constrain the reactive test gas mixture to an area close to the
      shock tube endwall, separating it from a specially formulated non-reactive buffer
      gas mixture. This second-generation Constrained Reaction Volume (CRV) strategy
      enables near-constant-pressure shock tube test conditions for reactive
      experiments behind reflected shocks, thereby enabling improved modeling of the
      reactive flow field. Here we provide details of the design and operation of the
      new shock tube. In addition, we detail special buffer gas tailoring procedures,
      analyze the buffer/test gas interactions that occur on gate valve opening, and
      outline the size range of fuels that can be studied using the CRV technique in
      this facility. Finally, we present example low-temperature ignition delay time
      data to illustrate the CRV shock tube's performance. 

PMID- 24880417
TI  - Compact, compression-free, displaceable, and resealable vacuum feedthrough with
      built-in strain relief for sensitive components such as optical fibers.
AB  - For the direct fiber coupling of small optical measurement cells, we developed a
      new compact vacuum feedthrough for glass fibers and other similarly shaped
      objects that are compact and that offer the possibility of adjusting the fiber in
      longitudinal and in circular direction. The feedthrough assembly avoids
      compression or torsion on the fiber and thus protects, e.g., highly frangible
      fiber materials. In the following, we will present a brief simulation of the
      tightness requirements for low-pressure and low-concentration water vapor
      measurements and we will explain an integrated concept for a displaceable and
      self-adjustable, compression-free, compact, ultra-high vacuum, resealable
      feedthrough with good strain relief. The feedthrough has been successfully tested
      in a laboratory test facility and in several extractive airborne tunable diode
      laser absorption spectroscopy hygrometers. The leakage rate of the feedthrough
      presented here was tested via a helium leak searcher and was quantified further
      in an 8-week vacuum measurement campaign. The leakage rate is determined to be
      0.41 +/- 0.04 * 10(-9) hPa l/s, which--to our knowledge--is the first time a
      leakage rate for such a feedthrough has been quantified.

PMID- 24880418
TI  - High velocity flyer plates launched by magnetic pressure on pulsed power
      generator CQ-4 and applied in shock Hugoniot experiments.
AB  - High velocity flyer plates with good flatness and some thickness have being
      widely used to the field of shock physics for characterizations of materials
      under dynamical loading. The techniques of magnetically driven high-velocity
      flyer plates are further researched based on our pulsed power generators CQ-4 and
      some good results got on Sandia's Z machine. With large current of several mega
      amperes, the loading surface of electrode panel will suffer acute phase
      transitions caused from magnetic diffusion and Joule heating, and the thickness
      and flatness of the flyer plates will change with time. In order to obtain the
      flyer plates with high performances for shock physics, some researches on
      electrode panels were done by means of LS-DYNA980 software with electro-magnetic
      package. Two typical configurations for high velocity flyer plates were compared
      from distribution uniformity of magnetic field in simulation. The results show
      that the configuration with counter-bore with "notch" and "ear" is better than
      the other. Then, with the better configuration panels, some experiments were
      designed and done to validate the simulation results and obtain high velocity
      flyer plates with good flatness for one-dimensional strain shock experiments on
      CQ-4. The velocity profiles of the flyer plates were measured by displacement
      interferometer systems for any reflectors. And the planarity of flyer plates was
      measured by using the optical fiber pins array for recording the flyer arrival
      time. The peak velocities of 8.7 km/s with initial dimension of 10 * 7.2 * 0.62
      mm for aluminum flyer plates have been achieved. And the flyer plate with initial
      size of 12 * 9.2 * 0.73 mm was accelerated to velocity of 6.5 km/s with the
      flatness of less than 11 ns in the central region of 6 mm in diameter and the
      effective thickness of about 0.220 mm. Based on these work, the symmetrical
      impact experiments were performed to obtain the high accuracy Hugoniot data of
      OFHC (oxygen free high conductance) copper on CQ-4. The experimental results
      agree well with previous experiment's data given by Mcqueen and Marsh [J. Appl.
      Phys. 31, 1253 (1960)] and Mitchell and Nellis [J. Appl. Phys. 52, 3363 (1981)],
      and the experimental uncertainty of shock wave velocity is less than 2.4%. 

PMID- 24880419
TI  - The differential Howland current source with high signal to noise ratio for
      bioimpedance measurement system.
AB  - The stability and signal to noise ratio (SNR) of the current source circuit are
      the important factors contributing to enhance the accuracy and sensitivity in
      bioimpedance measurement system. In this paper we propose a new differential
      Howland topology current source and evaluate its output characters by simulation
      and actual measurement. The results include (1) the output current and impedance
      in high frequencies are stabilized after compensation methods. And the stability
      of output current in the differential current source circuit (DCSC) is 0.2%. (2)
      The output impedance of two current circuits below the frequency of 200 KHz is
      above 1 MOmega, and below 1 MHz the output impedance can arrive to 200 KOmega.
      Then in total the output impedance of the DCSC is higher than that of the Howland
      current source circuit (HCSC). (3) The SNR of the DCSC are 85.64 dB and 65 dB in
      the simulation and actual measurement with 10 KHz, which illustrates that the
      DCSC effectively eliminates the common mode interference. (4) The maximum load in
      the DCSC is twice as much as that of the HCSC. Lastly a two-dimensional phantom
      electrical impedance tomography is well reconstructed with the proposed HCSC.
      Therefore, the measured performance shows that the DCSC can significantly improve
      the output impedance, the stability, the maximum load, and the SNR of the
      measurement system. 

PMID- 24880420
TI  - An experimental comparison of proportional-integral, sliding mode, and robust
      adaptive control for piezo-actuated nanopositioning stages.
AB  - This paper presents a comparative study of the proportional-integral (PI)
      control, sliding mode control (SMC), and robust adaptive control (RAC) for
      applications to piezo-actuated nanopositioning stages without the inverse
      hysteresis construction. For a fair comparison, the control parameters of the SMC
      and RAC are selected on the basis of the well-tuned parameters of the PI
      controller under same desired trajectories and sampling frequencies. The
      comparative results show that the RAC improves the tracking performance by 17 and
      37 times than the PI controller in terms of the maximum tracking error e(m) and
      the root mean tracking error e(rms), respectively, while the RAC improves the
      tracking performance by 7 and 9 times than the SMC in terms of e(m) and e(rms),
      respectively.

PMID- 24880421
TI  - Top-up operation at Pohang Light Source-II.
AB  - After three years of upgrading work, PLS-II (S. Shin, Commissioning of the PLS
      II, JINST, January 2013) is now successfully operating. The top-up operation of
      the 3 GeV linear accelerator had to be delayed because of some challenges
      encountered, and PLS-II was run in decay mode at the beginning in March 2012. The
      main difficulties encountered in the top-up operation of PLS-II are different
      levels between the linear accelerator and the storage ring, the 14 narrow gap in
      vacuum undulators in operation, and the full energy injection by 3 GeV linear
      accelerator. Large vertical emittance and energy jitter of the linac were the
      major obstacles that called for careful control of injected beam to reduce beam
      loss in the storage ring during injection. The following measures were taken to
      resolve these problems: (1) The high resolution Libera BPM (see http://www.i
      tech.si) was implemented to measure the beam trajectory and energy. (2) Three
      slit systems were installed to filter the beam edge. (3) De-Qing circuit was
      applied to the modulator system to improve the energy stability of injected beam.
      As a result, the radiation by beam loss during injection is reduced drastically,
      and the top-up mode has been successfully operating since 19th March 2013. In
      this paper, we describe the experimental results of the PLS-II top-up operation
      and the improvement plan. 

PMID- 24880422
TI  - Enhanced broadband ultrafast detection of ultraviolet emission using optical Kerr
      gating.
AB  - We demonstrate a high-sensitivity ultrafast emission spectrometer based on the
      optical Kerr effect that time resolves emission simultaneously in the ultraviolet
      and visible ranges. We show that using benzene as the Kerr medium leads to the
      optimal balance between time-resolution and sensitivity of the optical shutter
      with low losses due to ultraviolet absorption. Using this medium together with
      high contrast broadband polarizers and charge-coupled device detection, we
      achieve efficient detection of emission transients (bandwidth >1.5 eV) in a time
      bin of ~500 fs. To highlight the distinctive insights that can be gained by
      resolving complex subpicosecond dynamics in a single experiment, we present UV
      visible transient emission spectra of technologically relevant wide bandgap zinc
      oxide. With an enhanced broadband detection, subpicosecond effects such as
      thermalization, bandgap renormalization, and carrier trapping can be easily
      assessed, with ramifications for optoelectronics and energy-related technologies.

PMID- 24880423
TI  - Magnetic field uniformity of the practical tri-axial Helmholtz coils systems.
AB  - In this paper, effects of the assembly misalignments and the manufacturing
      mismatches on the magnetic field uniformity of a practical tri-axial Helmholtz
      coils system have been modeled mathematically. These undesired effects regularly
      occur in any practical tri-axial Helmholtz coils system. To confirm the
      mathematical calculations, a tri-axial Helmholtz coils system has been
      constructed and the uniformity of its magnetic field has been measured under
      different conditions. The experimental results are in good agreement with the
      mathematical analyses. 

PMID- 24880424
TI  - An atomic layer deposition chamber for in situ x-ray diffraction and scattering
      analysis.
AB  - The crystal structure of thin films grown by atomic layer deposition (ALD) will
      determine important performance properties such as conductivity, breakdown
      voltage, and catalytic activity. We report the design of an atomic layer
      deposition chamber for in situ x-ray analysis that can be used to monitor changes
      to the crystal structural during ALD. The application of the chamber is
      demonstrated for Pt ALD on amorphous SiO2 and SrTiO3 (001) using synchrotron
      based high resolution x-ray diffraction, grazing incidence x-ray diffraction, and
      grazing incidence small angle scattering. 

PMID- 24880425
TI  - A synchrotron-radiation-based variable angle ellipsometer for the visible to
      vacuum ultraviolet spectral range.
AB  - A rotating analyzer spectroscopic polarimeter and ellipsometer with a wide-range
      theta-2theta goniometer installed at the Insertion Device Beamline of the
      Metrology Light Source in Berlin is presented. With a combination of transmission
      and reflection-based polarizing elements and the inherent degree of polarization
      of the undulator radiation, this ellipsometer is able to cover photon energies
      from about 2 eV up to 40 eV. Additionally, a new compensator design based on a
      CaF2 Fresnel rhomb is presented. This compensator allows ellipsometric
      measurements with circular polarization in the vacuum ultraviolet spectral range
      and thus, for example, the characterization of depolarizing samples. The new
      instrument was initially used for the characterization of the polarization of the
      beamline. The technical capabilities of the ellipsometer are demonstrated by a
      cohesive wide-range measurement of the dielectric function of epitaxially grown
      ZnO.

PMID- 24880426
TI  - Note: Broadly tunable all-fiber ytterbium laser with 0.05 nm spectral width based
      on multimode interference filter.
AB  - A multimode interference filter with narrow transmission bandwidth and large self
      imaging wavelength interval is constructed and implemented in an ytterbium doped
      fiber laser in all-fiber format for broad wavelength tunability as well as narrow
      spectral width of the output beam. The peak transmission wavelength of the
      multimode interference filter was tuned with the help of a standard in-fiber
      polarization controller. With this simple mechanism more than 30 nm (1038 nm-1070
      nm) tuning range is demonstrated. The spectral width of the output beam from the
      laser was measured to be 0.05 nm. 

PMID- 24880427
TI  - Note: On the measurement of plasma potential fluctuations using emissive probes.
AB  - In this Note, it is pointed out that emissive probes cannot be used to directly
      and reliably measure plasma potential fluctuations. An experimentally validated
      model demonstrates indeed that the floating potential fluctuations of an emissive
      probe which floats at the mean plasma potential depend not only on the plasma
      potential fluctuations but also on electron density and temperature fluctuations.

PMID- 24880428
TI  - Note: Multi-pass Thomson scattering measurement on the TST-2 spherical tokamak.
AB  - In multi-pass Thomson scattering (TS) scheme, a laser pulse makes multiple round
      trips through the plasma, and the effective laser energy is enhanced, and we can
      increase the signal-to-noise ratio as a result. We have developed a coaxial
      optical cavity in which a laser pulse is confined, and we performed TS
      measurements using the coaxial cavity in tokamak plasmas for the first time. In
      the optical cavity, the laser energy attenuation was approximately 30% in each
      round trip, and we achieved a photon number gain of about 3 compared with that
      obtained in the first round trip. In addition, the temperature measurement
      accuracy was improved by accumulating the first three round trip waveforms. 

PMID- 24880429
TI  - Note: Artificial neural networks for the automated analysis of force map data in
      atomic force microscopy.
AB  - Force curves recorded with the atomic force microscope on structured samples
      often show an irregular force versus indentation behavior. An analysis of such
      curves using standard contact models (e.g., the Sneddon model) would generate
      inaccurate Young's moduli. A critical inspection of the force curve shape is
      therefore necessary for estimating the reliability of the generated Young's
      modulus. We used a trained artificial neural network to automatically recognize
      curves of "good" and of "bad" quality. This is especially useful for improving
      the analysis of force maps that consist of a large number of force curves. 

PMID- 24880430
TI  - Note: Proton irradiation at kilowatt-power and neutron production from a free
      surface liquid-lithium target.
AB  - The free-surface Liquid-Lithium Target, recently developed at Soreq Applied
      Research Accelerator Facility (SARAF), was successfully used with a 1.9 MeV, 1.2
      mA (2.3 kW) continuous-wave proton beam. Neutrons (~2 * 10(10) n/s having a peak
      energy of ~27 keV) from the (7)Li(p,n)(7)Be reaction were detected with a fission
      chamber detector and by gold activation targets positioned in the forward
      direction. The setup is being used for nuclear astrophysics experiments to study
      neutron-induced reactions at stellar energies and to demonstrate the feasibility
      of accelerator-based boron neutron capture therapy.

PMID- 24880432
TI  - Note: Real-time absolute air refractometer.
AB  - We present a real-time absolute air refractometer benefiting from the synthetic
      pseudo-wavelength (SPW) method. Based on laser heterodyne interferometry, the SPW
      method uses three vacuum cells with specific lengths to synthesize a set of
      synthetic pseudo-wavelengths, by combination of which the refractive index can be
      determined directly without ambiguity. In addition, owing to the parallel
      arrangement of the vacuum cells in the optical path, the measured data can be
      collected simultaneously so that one measurement process can be less than 2 ms.
      The real-time feature makes it possible for instantaneous compensation for laser
      interferometers. 

PMID- 24880431
TI  - Note: A novel piezoelectrically driven pipette using centrifugal force.
AB  - This paper proposes a novel piezoelectrically driven pipette, which utilizes
      centrifugal force in swing motion of a vibrating tube as the driving force, to
      input and output liquid at first bending resonant frequency. Control circuit
      capable of frequency tracking is designed. Pulse volume changing with different
      driving voltage amplitude, driving frequency, tip size, and target reagents are
      studied in experiments. The output pulse volume of a prototype pipette driven by
      voltage of 560 V(pp) at 175.9 Hz is 43.2 MUl with a variation of +/-3.5%. Minimum
      water spots of 3 MUl can be deposited in this manner. This pipette represents an
      alternative to standard liquid transfer techniques in chemical or biological
      experiments.

PMID- 24880433
TI  - Note: A rigid piezo motor with large output force and an effective method to
      reduce sliding friction force.
AB  - We present a completely practical TunaDrive piezo motor. It consists of a central
      piezo stack sandwiched by two arm piezo stacks and two leg piezo stacks,
      respectively, which is then sandwiched and spring-clamped by a pair of parallel
      polished sapphire rods. It works by alternatively fast expanding and contracting
      the arm/leg stacks while slowly expanding/contracting the central stack
      simultaneously. The key point is that sufficiently fast expanding and contracting
      a limb stack can make its two sliding friction forces well cancel, resulting in
      the total sliding friction force is <10% of the total static friction force,
      which can help increase output force greatly. The piezo motor's high compactness,
      precision, and output force make it perfect in building a high-quality harsh
      condition (vibration resistant) atomic resolution scanning probe microscope. 

PMID- 24880434
TI  - Note: Raman microspectroscopy integrated with fluorescence and dark field
      imaging.
AB  - A Raman detection platform integrated with both fluorescence and dark field
      microscopes was built for in situ Raman detection with the assistance of
      fluorescence and dark field imaging to locate the target micro regions. Cells and
      organelles can be easily found via fluorescence imaging with labeling techniques.
      Besides, nano-sized particles could be observed and located by dark field
      microscopes. Therefore, comparing with the commercial Raman spectrometers, much
      more researches based on Raman spectroscopy could be carried out on this
      integrated Raman platform, especially in the fields of analyzing biological
      tissues and subwavelength samples. 

PMID- 24880437
TI  - Effects of BMP-2 and FGF2 on the osteogenesis of bone marrow-derived mesenchymal
      stem cells in hindlimb-unloaded rats.
AB  - Hindlimb unloading, as a simulation of microgravity, decreases the osteogenic
      potential of mesenchymal stem cells (MSCs) from hindlimb femur of rat. We
      simulated the microgravity by 28-day of hindlimb unloading for male Sprague
      Dawley rat, and performed intramuscular injection of BMP-2 and FGF2 at a given
      interval during hindlimb unloading. Then, the bone marrow (BM) was collected from
      hindlimb femur of rat. MSCs were isolated from BM, cultured for four passages,
      and then induced for osteogenesis. The results revealed that the hindlimb
      unloading decreased the osteogenic potential of MSCs and also the expression of
      osteoblast gene marker mRNAs in cells induced by osteogenic conditions. Hindlimb
      unloading for 28 days resulted in the decrease of vinculin-containing focal
      adhesion in MSCs. During hindlimb unloading, the interval intramuscular injection
      of BMP-2 or FGF2 alone could increase the osteogenic potential of MSCs and the
      expression of osteoblast gene marker mRNA. However, the effect of BMP-2 or FGF2
      injection alone was significantly lower than that of combination injection of
      both factors. The further examination showed that the intramuscular injection of
      BMP-2 promoted the expression of Runx2 mRNA and that the intramuscular injection
      of FGF2 increased the phosphorylation of ERK and Runx2. Nevertheless, the
      intramuscular injection of any factor could not increase the formation of
      vinculin-containing focal adhesions in MSCs. This suggests that BMP-2 should
      increase the expression of Runx2, and that the activation of Runx2 should be
      promoted by the FGF2 signaling pathway which activated ERK/Runx2. The activation
      of this signaling pathway should not lie on the formation of vinculin-containing
      focal adhesions.

PMID- 24880436
TI  - Antiviral potential of lactic acid bacteria and their bacteriocins.
AB  - Emerging resistance to antiviral agents is a growing public health concern
      worldwide as it was reported for respiratory, sexually transmitted and enteric
      viruses. Therefore, there is a growing demand for new, unconventional antiviral
      agents which may serve as an alternative to the currently used drugs. Meanwhile,
      published literature continues shedding the light on the potency of lactic acid
      bacteria (LAB) and their bacteriocins as antiviral agents. Health-promoting LAB
      probiotics may exert their antiviral activity by (1) direct probiotic-virus
      interaction; (2) production of antiviral inhibitory metabolites; and/or (3) via
      stimulation of the immune system. The aim of this review was to highlight the
      antiviral activity of LAB and substances they produce with antiviral activity. 

PMID- 24880439
TI  - Versatility of nasolabial flaps in oral cavity reconstructions.
AB  - OBJECTIVES: Describe the techniques involved and the results obtained witn
      nasolabial flaps in small and medium-sized defects of the oral cavity. The
      procedure is an easy resconstructive option with a high success rate and with
      very good aesthetic and functional outcomes. STUDY DESIGN: A retrospective
      analysis of 16 nasolabial flap reconstructions in 15 oncological patients with
      oral cavity defects undergoing single-stage surgical interventions. We evaluate
      the tumor type, its location, size, the resective and reconstructive techniques
      involved, as well as any complications. RESULTS: Out of 15 patients, 9 were male
      and 6 female, with ages ranging from 60-85 years. The primary tumor was located
      in the mandibular or maxillary gingiva in 7 patients, the lateral margin of the
      tongue in 5, the floor of the mouth in 3 and the mandibular symphysis in a single
      patient. The tumors were of a small to medium size. All patients underwent
      intraoral resections. In most cases, a cervical dissection was performed. All
      flaps were completed as single-stage surgical interventions, with 14 unilateral
      and 2 bilateral procedures. Five patients had received radiotherapy treatment for
      previous tumors. During the follow up period, which ranged from 4 months to 8
      years, only one patient required their flap to be thinned, there were two
      incidents of surgical wound dehiscence, two hematomas and one orocutaneous
      fistula, none of which affected the survival of the flap. CONCLUSIONS: The
      nasolabial flap proves highly versatile in oral cavity reconstructions, coupled
      with a minimal morbidity of the donor region and good aesthetic and functional
      results. Its high vascularity allows for cervical dissections to be carried out
      or even for radiotherapy to be administered prior to it. It is straightforward,
      safe, and carrying it out as a single-stage intervention makes it the ideal
      surgical option for small to medium intraoral defects in edentulous patients with
      other comorbidities.

PMID- 24880438
TI  - Optimum calcium concentration: a crucial factor in regulating sperm motility in
      vitro.
AB  - Sperm motility can be maintained in vitro by incubation in a defined medium under
      specific conditions. In most studies, the exact role of various constituents of
      epididymal fluid, including calcium, has remained obscure. Most of the culture
      media have included millimolar concentrations of calcium, but previous reports
      have indicated that millimolar calcium inhibits sperm motility. In this present
      study, we sought the optimum concentration of extracellular calcium required for
      optimum sperm motility. This study showed that extracellular calcium has a
      concentration-dependent biphasic role in motility regulation. It promoted
      motility and velocity at lower (10 uM) concentration whereas notably inhibited it
      at higher concentrations. When external membrane-bound calcium was removed by
      ethylene glycol tetraacetic acid, motility decreased considerably. To confirm the
      motility-inhibiting role of calcium above 10 uM, a sperm motility-stimulating
      protein (MSP) recently reported from our laboratory was used which at 0.9 MUM
      induces motility in 60-70 % cells. Calcium at 10 uM had no appreciable effect on
      the motility-promoting activity of the MSP but depressed the activity above 10
      uM. Thus, our present results emphasize the biphasic role of extracellular
      calcium and the importance of its optimum concentration in different buffers and
      media used for sperm motility initiation.

PMID- 24880440
TI  - Alveolar graft in the cleft lip and palate patient: review of 104 cases.
AB  - INTRODUCTION: Alveolar bone grafting is a vital part of the rehabilitation of
      cleft patients. The factors that have been most frequently associated with the
      success of the graft are the age at grafting and the pre-grafting orthodontic
      treatment. OBJECTIVES: 1) Describe the cases of alveolar bone grafts performed at
      the Maxilofacial Unit of Hospital Sant Joan de Deu, Barcelona (HSJD); and 2)
      Analyze the success/failure of alveolar grafts and related variables. MATERIAL
      AND METHODS: Descriptive retrospective study using a sample of 104 patients who
      underwent a secondary alveolar graft at the Craniofacial Unit of HSJD between
      1998 and 2012. The graft was done by the same surgeon in all patients using bone
      from the iliac crest. RESULTS: 70% of the patients underwent the procedure before
      the age of 15 (median 14.45 years); 70% of the graft patients underwent pre-graft
      maxillary expansion. A total of 100 cases were recorded as successful (median age
      of 14.58 years, 68 underwent pre-graft expansion) and only 4 were recorded as
      failures (median age of 17.62 years, 3 underwent pre-graft expansion). We did not
      find statistically significant differences in age at the time of grafting or pre
      surgical expansion when comparing the success and failure groups. We found the
      success rate of the graft to be 96.2%. CONCLUSIONS: The number of failures was
      too small to establish a statistically significant conclusion in our sample
      regarding the age at grafting and pre-grafting expansion. The use of alveolar
      bone grafting from the iliac crest has a very high success rate with a very low
      incidence of complications. Existing controversies regarding secondary bone
      grafting and the wide range of success rates found in the literature suggest that
      it is necessary to establish a specific treatment protocol that ensures the
      success of this procedure.

PMID- 24880441
TI  - Epidermal growth factor receptor expression in different subtypes of oral
      lichenoid disease.
AB  - The oral lichenoid disease (OLD) includes different chronic inflammatory
      processes such as oral lichen planus (OLP) and oral lichenoid lesions (OLL), both
      entities with controversial diagnosis and malignant potential. Epidermal growth
      factor receptor (EFGR) is an important oral carcinogenesis biomarker and
      overexpressed in several oral potentially malignant disorders. OBJECTIVES: To
      analyze the EGFR expression in the OLD to find differences between OLP and OLL,
      and to correlate it with the main clinical and pathological features. MATERIAL
      AND METHODS: Forty-four OLD cases were studied and classified according to their
      clinical (Group C1: only papular lesions / Group C2: papular and other lesions)
      and histopathological features (Group HT: OLP-typical / Group HC: OLP-compatible)
      based in previous published criteria. Standard immunohistochemical identification
      of EGFR protein was performed. Comparative and descriptive statistical analyses
      were performed. RESULTS: Thirty-five cases (79.5%) showed EGFR overexpression
      without significant differences between clinical and histopathological groups
      (p<0.05). Histological groups showed significant differences in the EGFR
      expression pattern (p=0.016). Conlusions: All OLD samples showed high EGFR
      expression. The type of clinical lesion was not related with EGFR expression;
      however, there are differences in the EGFR expression pattern between
      histological groups that may be related with a different biological profile and
      malignant risk.

PMID- 24880442
TI  - Topical treatment of oral lichen planus with anthocyanins.
AB  - BACKGROUND: Oxidative stress is involved in oral lichen planus (OLP)
      pathogenesis; meanwhile anthocyanins are natural antioxidants present in grapes
      skin. OBJECTIVES: The aim of this research was to verify the utility of
      anthocyanins, extracted from grapes skin, for the local treatment of oral lichen
      planus and to compare it with clobetasol propionate- neomycin -nystatin cream (CP
      NN). STUDY DESIGN: Prospective, non-randomized study, with control group. Fifty
      two patients with OLP were included. We divided patients into two categories:
      erosive oral lichen planus (EOLP) and non erosive oral lichen planus (NEOLP). 38
      had EOLP (17 cases and 21 controls) and 14 presented NEOLP types (9 cases and 5
      controls).Cases received local treatment with anthocyanins from grapes and
      controls, were treated with CP-NN. The clinical evolution of patients was
      followed up during six months. RESULTS: The patients had a therapeutic response
      with anthocyanins. This was better than CP-NN treatment for patients with EOLP,
      in improving the involvement score of the oral mucosa and in the morphometric
      study of the affected areas. In EOLP there were no statistically significant
      differences in: therapeutic response time, the evolution of pain, or the relapse
      rate between the two groups. With respect to the treatment of NEOLP there was
      improved pain relief in the group treated with anthocyanins. This was not
      observed with CP-NN. The resting analized variables showed no significant
      difference with both treatments. CONCLUSIONS: OLP has a favorable response to
      local treatment with anthocyanins from grapes. We found an equal to or better
      response than with CP-NN treatment. Many of our patients have systemic diseases,
      which may contraindicate the use of steroids. With regard to this particular
      group, the use of this natural antioxidant present in the diet is considered
      advantageous.

PMID- 24880443
TI  - Effect of Erythrinamu lungu on anxiety during extraction of third molars.
AB  - OBJECTIVES: The aim of the present study was to evaluate the effect of
      Erythrinamu lungu on the control of dental anxiety in patients who had under gone
      bilateral extraction of asymptomatic, impacted mandibular third molars. MATERIAL
      AND METHODS: In a randomized, double-blind, crossover study, 30 healthy
      volunteers (5 men and 25 women, over 18 years of age), received either 500mg of
      E.mulungu (MulunguMatusa(r)) or 500 mg of placebo, p.o., one hour before surgical
      procedure. The level ofanxiety was assessed through questionnaire sand physical
      parameters, such as blood pressure, heart rate andoxygen saturation. Data were
      analyzed by Chi-square test, ANOVA (Tukey test) and Friedman with significance
      level of 5%. RESULTS: A higher preference (Chi-square, p = 0.0062) for E. mulungu
      was observed for both genders. Volunteers with higher anxiety levels tended to to
      prefer E. mulungu. No statistically significant differences were verified in
      blood pressure (one-way ANOVA, p = 0.1259), heart rate (Friedman, p> 0.05) and
      oxygen saturation (Friedman, p = 0.7664) among periods and types of treatments.
      CONCLUSIONS: E. mulungu showed an anxiolytic effect without significant changes
      in physiological parameters. It could be considered as an alternative to control
      the anxiety in adult patients undergoing mandibular thirdmolars surgery.

PMID- 24880444
TI  - Analysis of 415 adverse events in dental practice in Spain from 2000 to 2010.
AB  - INTRODUCTION: The effort to increase patient safety has become one of the main
      focal points of all health care professions, despite the fact that, in the field
      of dentistry, initiatives have come late and been less ambitious. The main
      objective of patient safety is to avoid preventable adverse events to the
      greatest extent possible and to limit the negative consequences of those which
      are unpreventable. Therefore, it is essential to ascertain what adverse events
      occur in each dental care activity in order to study them in-depth and propose
      measures for prevention. OBJECTIVES: To ascertain the characteristics of the
      adverse events which originate from dental care, to classify them in accordance
      with type and origin, to determine their causes and consequences, and to detect
      the factors which facilitated their occurrence. MATERIAL AND METHOD: This study
      includes the general data from the series of adverse dental vents of the Spanish
      Observatory for Dental Patient Safety (OESPO) after the study and analysis of
      4,149 legal claims (both in and out of court) based on dental malpractice from
      the years of 2000 to 2010 in Spain. RESULTS: Implant treatments, endodontics and
      oral surgery display the highest frequencies of adverse events in this series
      (25.5%, 20.7% and 20.4% respectively). Likewise, according to the results, up to
      44.3% of the adverse events which took place were due to predictable and
      preventable errors and complications. CONCLUSION: A very significant percentage
      were due to foreseeable and preventable errors and complications that should not
      have occurred.

PMID- 24880445
TI  - Immediate loading with fixed full-arch prostheses in the maxilla: review of the
      literature.
AB  - OBJECTIVES: To critically review the evidence-based literature on immediate
      loading of implants with fixed full-arch prostheses in the maxilla to determine
      1) currently recommended performance criteria and 2) the outcomes that can be
      expected with this procedure. STUDY DESING: Studies from 2001 to 2011 on
      immediate loading with fixed full-arch maxillary prostheses were reviewed.
      Clinical series with at least 5 patients and 12 months of follow-up were
      included. Case reports, studies with missing data and repeatedly published
      studies were excluded. In each study the following was assessed: type of study,
      implant type, number of patients, number of implants, number of implants per
      patient, use of post-extraction implants, minimum implant length and diameter,
      type of prosthesis, time until loading, implant survival rate, prosthesis
      survival rate, marginal bone loss, complications and mean follow-up time.
      Criteria for patient selection, implant primary stability and bone regeneration
      were also studied. RESULTS: Thirteen studies were included, reporting a total of
      2484 immediately loaded implants in 365 patients. Currently accepted performance
      criteria regarding patient and implant selection, and surgical and prosthetic
      procedures were deduced from the reviewed articles. Implant survival rates went
      from 87.5% to 100%, prosthesis survival rates from 93.8% to 100% and radiographic
      marginal bone loss from 0.8 mm to 1.6 mm.No intraoperative complications and only
      minor prosthetic complications were reported. CONCLUSIONS: The literature on
      immediate loading with fixed full-arch prostheses in the maxilla shows that a
      successful outcome can be expected if adequate criteria are used to evaluate the
      patient, choose the implant and perform the surgical and prosthetic treatment.
      Lack of homogeneity within studies limits the relevance of the conclusions that
      can be drawn, and more controlled randomized studies are necessary to enable
      comparison between the immediate and the conventional loading procedures.

PMID- 24880446
TI  - Verrucous carcinoma of the oral mucosa: an epidemiological and follow-up study of
      patients treated with surgery in 5 last years.
AB  - INTRODUCTION: Oral Verrucous Carcinoma (OVC) is described apart of the Squamous
      Cell Carcinoma (SCC) due to its specific properties. The objective of our study
      is to show our series of cases of OVC and to compare with the SCC in terms of
      clinical manifestations, epidemiology, histopathology, treatment and follow-up.
      MATERIAL AND METHODS: This is a retrospective study of all the OVC treated in our
      department between January-2007 and December-2011. The analyzed variables were
      sex, age, localization in the oral cavity, histopathology, number of biopsies
      needed to diagnose OVC, TNM classification, treatment and recurrences during
      follow-up. RESULTS: Our sample was composed by n=14 patients, 57% female, with a
      mean age of 69.14 years. The most common localization was buccal mucosa (n=5).
      Seven patients were diagnosed of OVC with the first biopsy. TNM classification
      was: pT1: 7 patients, pT2: 3 patients, pT3: 3 patients, pT4: 1 patient. No
      cervical metastases were observed either in cervical neck dissection or during
      the follow-up of the patients. The treatment was surgery with clinical resection
      margins up to 1 cm in all cases, followed by radiotherapy in selected cases. Only
      n=1 patient (7.69%) presented a recurrence after 34 months of follow-up. The
      overall survival rate was 92.85%. CONCLUSIONS: In our population, OVC represents
      the 6.16% of all oral cavity and oropharynx cancer, and is more frequent in
      female patients above 70 years old. It uses to rise over a previous lesion, and
      usually affects the buccal mucosa. In patients with high suspicious lesions, more
      than one biopsy may be needed to diagnose OVC. No patient showed cervical
      dissemination. In our experience, treatment based on local resection, without
      cervical neck dissection, could be a good option for these patients.

PMID- 24880447
TI  - State anxiety and depression as factors modulating and influencing postoperative
      pain in dental implant surgery. A prospective clinical survey.
AB  - OBJECTIVES: To determine whether preoperative state anxiety and depression
      modulate or influence objective and subjective postoperative pain following
      dental implant insertion. STUDY DESIGN: Prospective, clinical study with 7-day
      follow-up of a sample of 105 subjects who preoperatively completed the state
      anxiety questionnaire (STAI-E) and Beck Depression Inventory (BDI) and
      postoperatively, at 2 and 7 days, recorded objective pain with the Semmes
      Weinstein mechanical esthesiometer (SW test) and subjective pain with the Visual
      Analog Scale (VAS). RESULTS: 85.6% and 81.5% of patients, respectively, recorded
      no signs of state anxiety or depression. The correlation between anxiety and
      depression for both maxillary bones was the lower (P=0.02). The correlation
      between subjective and objective pain at 2 and 7 days, and the anatomic regions
      intervened, was statistically significant in the mandible at day 7 (P<0.01), and
      highly significant (P<0.001) for the other variables. The correlation between
      state anxiety and objective pain at day 7 was nearly statistically significant
      (P=0.07). CONCLUSIONS: The correlation between state anxiety and depression, and
      objective and subjective pain at day 7 was not statistically significant. A
      strong correlation was found between objective and subjective pain in the
      immediate postoperative period.

PMID- 24880448
TI  - Effectiveness of Toki's criteria and determination of variables for
      identification of HPV L1 protein in oral lesions.
AB  - OBJECTIVE: To evaluate the effectiveness of Toki's criteria in identifying the
      HPV L1 protein in oral lesions with the use of immunohistochemistry (IHC) and to
      determine which criteria optimize such identification. STUDY DESIGN:
      Retrospective study of 277 cases diagnosed as HPV lesions at 22 years. Tests of
      sensitivity, specificity, positive predictive value (PPV), negative predictive
      value (NPV), kappa coefficients, and chi2 values, as well as two logistic
      regression analyses (p<=0.05), were conducted. RESULTS: Of the lesions studied,
      96.4% (267 of 277) were positive for HPV using Toki's criteria and 28.5% (79 of
      277) were positive for L1 by IHC. Toki's criteria showed sensitivity=93.67%,
      specificity=2.53%, PPV=6.99%, and NPV=46.55%. Neither concordance nor
      statistically significant associations were observed between both tests. The
      logistic regression of Toki's criteria was useful in the diagnosis of L1,
      correctly classified 71.8% of the lesions positive for L1, and showed a Hosmer
      Lemeshow adjustment of p=0.614 and a Nagelkerke's coefficient of determination of
      6.8%. The explanatory variables statistically significant at p<=0.05 were
      dyskeratosis (p=0.01) and papillomatosis (p=0.04). Forty-nine independent
      variables (clinical and histopathologic) were involved in the second regression
      analysis. The model correctly classified 85.2% of the lesions and showed a Hosmer
      Lemeshow adjustment of p=0.696 and a Nagelkerke's coefficient of determination of
      60.2%. The explanatory variables statistically significant at p<=0.05 were: age
      younger than 35 years (p=0.001), multiple lesions (p=0.031), hyperorthokeratosis
      (p=0.019), focal intracellular edema (p=0.002), and the presence of 1 to more
      than 5 cells with degenerative changes in their nucleus (p=0.048). CONCLUSIONS:
      Toki's criteria are not adequate to make a diagnosis of lesions by HPV in the
      mouth, but the logistic regression analysis showed clinical and histopathologic
      variables which optimize the identification of lesions through the L1 protein.
      However, a PCR study is advisable when the presence of high-risk HPV is
      suspected.

PMID- 24880449
TI  - Comparative trial between the use of amoxicillin and amoxicillin clavulanate in
      the removal of third molars.
AB  - OBJECTIVE: The purpose of this study was to compare the use of amoxicillin (1g)
      vs amoxicillin and clavulanate (875/125mg) after extraction of retained third
      molars for prevention of infectious complications. STUDY DESIGN: The study
      involved 546 patients attending for removal a retained third molar and divided in
      to two groups: Group 1 - amoxicillin and clavunate (875/125mg) group (n=257) and
      Group 2 - amoxicillin (1g) group (n=289). All patients were recalled for
      investigating the possibility of infection, presence of diarrhea and further
      analgesic intake. RESULTS: From a total of 546 patients, the frequency of
      infection was 1.4%, without no statistically differences between the two groups.
      Group 1 showed statistically higher presence of patients with gastrointestinal
      complications (p>0.05). In 546 patients, 2.7% of patients reported severe pain
      that would not relieve with medication. CONCLUSION: The results of our study show
      that the use of amoxicillin (1g) and amoxicillin and clavunate (875/125mg) is
      similar efficacious in preventing infection after retained third molar extraction
      but amoxicillin and clavunate (875/125mg) produces more gastrointestinal
      discomfort.

PMID- 24880450
TI  - P53 gene codon 72 polymorphism in patients with oral squamous cell carcinoma in
      the population of northern Iran.
AB  - OBJECTIVES: Squamous cell carcinoma is the most common cancer of the oral cavity,
      and several etiologic factors are involved in its developing. Single nucleotide
      polymorphism (SNP) of the P53 gene codon 72 (P53c72) changes the structure of the
      protein and affects its activity. The prevalence of P53c72 different genotypes,
      which seems to vary with race and geographic location, has shown a strong
      correlation with many types of human cancers. The aim of this study was to
      investigate the correlation between P53c72polymorphism and risk of oral squamous
      cell carcinoma (OSCC) in the heavily populated Gilan Province in northern Iran.
      DESIGN OF STUDY: This case-control study was done on 55 paraffin-embedded samples
      from OSCC patients and 100 samples of non-dysplastic oral cavity lesions. The
      P53c72 genotypes were determined using the ARMS-PCR method. SPSS-15 software was
      used for statistical analysis. RESULTS: There were no significant statistical
      differences found between the prevalence of different P53c72 genotypes in the
      OSCC group vs. the control. However, the Pro/Pro genotype in OSCC samples showed
      a strong correlation with age, as 70% of such patients were below 50 years old.
      Interestingly, a large portion (40%) of the patients with the Pro/Pro genotype
      had the tumor in the lip area. CONCLUSIONS: Although P53c72 polymorphism does not
      appear to be a predisposing factor for OSCC in the population of Northern Iran,
      the Pro/Pro genotype could be considered as a risk factor for OSCC in adults
      below 50 years old and the anatomical location of the tumor.

PMID- 24880451
TI  - Optimization of buffer solutions to analyze inflammatory cytokines in gingival
      crevicular fluid by multiplex flow cytometry.
AB  - OBJECTIVE: the aim of this study was to test two buffer solutions in order to
      attain a reliable and reproducible analysis of inflammatory cytokines (IL-1beta,
      IL-6, TNF-alpha, OPG, OPN and OC), in gingival crevicular fluid (GCF) by flow
      cytometry. MATERIAL AND METHODS: GCF samples from healthy volunteers were
      collected with perio-paper strips and diluted either in phosphate buffered saline
      (PBS) or Tris-HCl buffer, with and without protease inhibitors (PI). Cytokine
      immunoassays were carried out by flow cytometry (Luminex Xmap 200) generating
      standard curves. RESULTS: standards curves generated with the use of phosphate
      buffered saline (PBS) demonstrated best adjustment for cytokines IL-1beta, IL-6
      and TNF- alpha levels, when using Tris-HCl (p<0.05). CONCLUSIONS: The use of PBS
      buffer with the addition of PI provided reliable measurements of inflammatory
      biomarkers in GCF samples of healthy volunteers.

PMID- 24880452
TI  - Granular cell tumor of the oral cavity; a case series including a case of
      metachronous occurrence in the tongue and the lung.
AB  - The granular cell tumor (GCT) is a rare, benign tumor that most commonly occurs
      in the oral cavity, particularly in the anterior part of the tongue. In this
      study the experience with 16 patients with a GCT observed in a single Institution
      will be discussed. Although no radicality has been obtained in most cases,
      recurrences are rare. In one patient, a recurrence was noted four years after
      excision of the primary. In the same patient a pulmonary lesion occurred five
      years after excision of the recurrence in the oral cavity, most likely
      representing an example of metachronous occurrence and not a distant metastasis.
      Since recurrences and metachronous lesions are rare, as are distant metastases,
      routine follow-up does not seem warranted in patients treated for a granular cell
      tumor of the oral cavity. 

PMID- 24880453
TI  - The role of a labial salivary gland biopsy in the diagnostic procedure for
      Sjogren's syndrome; a study of 94 cases.
AB  - OBJECTIVES: The purpose of the present study is to examine the role of the
      outcome of the labial salivary gland biopsy (LSGB) in the diagnostic procedure of
      patients suspected of suffering from Sjogren's syndrome (SS). MATERIAL AND
      METHODS: In a retrospective study the result of histopathological assessment of
      94 consecutively taken labial salivary gland biopsies has been examined. For the
      diagnosis of SS the American-European Consensus Group classification (AECG, 2002)
      have been used. The outcome of the assessment has been discussed in relation to a
      recently reported classification provided by the American College of Rheumatology
      (ACR, 2012). RESULTS: In the 94 LSGBs support for a diagnosis of SS has been
      encountered in 24 out of 26 patients with SS. In the 68 patients with a negative
      diagnosis of SS only six positive LSGBs were observed. The sensitivity of the
      labial biopsy amounted 0.92; the specificity was 0.91, while the positive
      predictive value and the negative predictive value amounted 0.80 and 0.97
      respectively. LSGBs taken by or on the request of the departments of Rheumatology
      or Internal Medicine had a significant higher yield compared to LSGBs taken in
      other clinical departments. CONCLUSIONS: The LSGB may play a role in the
      diagnostic procedure of Sjogren's syndrome when using either the AECG
      classification or the ACR classification. A LSGB should preferably taken after
      counseling for the possible presence of SS by a department of Rheumatology or
      Internal Medicine since the yield of such biopsies is much higher than in
      patients who have not been counseled by these departments prior to the taking of
      a LSGB. When using the ACR classification, a positive serologic result and a
      positive ocular test make the taking of a LSGB redundant. Only in case of a
      negative serologic outcome or a negative result of the ocular test a LSGB is
      indicated. Since both the serologic test and the ocular test carry hardly any
      morbidity, these tests should, indeed, be performed first before considering to
      take a LSGB.

PMID- 24880455
TI  - Nucleoside-sparing antiretroviral regimens.
AB  - Nucleoside reverse transcriptase inhibitors (NRTIs) were the first drugs approved
      for use as antiretroviral therapy in patients infected with HIV. Despite the
      introduction of other classes of antiretroviral drugs, they remain an important
      component of combination regimens as recommended by many treatment guidelines.
      They also continue to be used in prevention of disease from mother to child,
      postexposure prophylaxis, and more recently for preexposure prophylaxis.
      Unfortunately, the toxicities associated with this class of drugs can limit their
      use. Although NRTI-sparing regimens are not currently recommended for first-line
      therapy there is an increasing amount of data supporting their use in both
      treatment-naive and in treatment-experienced patients. 

PMID- 24880454
TI  - Histopathologic risk factors in oral and oropharyngeal squamous cell carcinoma
      variants: an update with special reference to HPV-related carcinomas.
AB  - Accurate identification of the microscopic risk factors of oral and oropharyngeal
      (OP) squamous cell carcinomas (SCC) and their morphologic variants is of at most
      importance, as these generally determine treatment modalities, prognosis and
      overall patient outcome. The great majority of oral and oropharyngeal squamous
      cell carcinomas are microscopically described as kerartinizing squamous cell
      carcinoma (KSCC). They bear certain resemblance to keratinizing stratified
      squamous epithelium. Tobacco habits and excessive consumption of alcoholic
      beverages have been considered to be the main etiologic agents in these
      carcinomas. The tumors occurred in older patients more commonly affected the oral
      tongue and floor of the mouth with well established morphologic risk factors
      including tumor grade, pattern of invasion and perineural involvement. Within the
      last 30 years however, the advent and expanding prevalence of high risk human
      papillomavirus (HPV) as an important etiologic agent for head and neck squamous
      cell carcinoma, particularly in the OP, has resulted in a significant change in
      the established morphologic criteria for risk assessment. The majority of HPV
      relate carcinomas of the OP are nonkeratinizing squamous cell carcinoma (NKSCC).
      These tumors are found to be more responsive to treatment with a favorable
      patient outcome and good prognosis. Consequently, alterations in treatment
      protocols aimed at de-escalation are currently being evaluated. More recently,
      other morphologic variants that are HPV positive are reported with increasing
      frequency in the OP and other head and neck sites. As a result, several clinical
      and pathologic questions have emerged. Importantly, whether the virus is
      biologically active in these tumors and involved in their pathogenesis, and
      second, what are the clinical implications with regard to patient management and
      outcome in the HPV-related variants. Examples of HPV-related squamous cell
      carcinoma variants that will be addressed here are: basaloid squamous cell
      carcinoma (BSCC), undifferentiated carcinoma (UCa), papillary squamous carcinoma
      (PSCC) and small cell carcinoma. Some studies have suggested favorable prognosis
      in some variants, analogous to that of the (NKSCC), while others showed poorer
      outcome. So far the number of studies on this subject is limited and the number
      of cases evaluated in each investigation is few. Because of that, it is prudent
      at this stage, not to alter management protocols as a result of identification of
      HPV in these variants and to await additional information. 

PMID- 24880456
TI  - Optic perineuritis: a further case of visual loss and disc edema in children:
      intracranial hypertension as alternative hypothesis.

PMID- 24880459
TI  - The transcription factor ThPOK suppresses Runx3 and imposes CD4(+) lineage fate
      by inducing the SOCS suppressors of cytokine signaling.
AB  - Lineage fate in the thymus is determined by mutually exclusive expression of the
      transcription factors ThPOK and Runx3, with ThPOK imposing the CD4(+) lineage
      fate and Runx3 promoting the CD8(+) lineage fate. While it is known that cytokine
      signals induce thymocytes to express Runx3, it is not known how ThPOK prevents
      thymocytes from expressing Runx3 and adopting the CD8(+) lineage fate, nor is it
      understood why ThPOK itself imposes the CD4(+) lineage fate on thymocytes. We now
      report that genes encoding members of the SOCS (suppressor of cytokine signaling)
      family are critical targets of ThPOK and that their induction by ThPOK represses
      Runx3 expression and promotes the CD4(+) lineage fate. Thus, induction of SOCS
      encoding genes is the main mechanism by which ThPOK imposes the CD4(+) lineage
      fate in the thymus.

PMID- 24880461
TI  - Vascular endothelial growth factor receptor 2, but not S100A4 or S100A6,
      correlates with prolonged survival in advanced urothelial carcinoma.
AB  - OBJECTIVE: A major challenge in muscle-invasive urothelial carcinoma (UC) is to
      identify biomarkers that can predict disease prognosis and treatment response
      after cystectomy. Therefore, we analyzed the potential prognostic value of the
      proteins vascular endothelial growth factor receptor 2 (VEGFR2), S100A4, and
      S100A6 in UC. METHODS: Retrospective outcome data and tumor specimens from 83
      cystectomy patients with histologically confirmed invasive UC were included.
      Expression levels of VEGFR2 (also called flk-1 and KDR), S100A4, and S100A6 were
      analyzed in primary tumor tissue by immunohistochemistry. RESULTS:
      Immunohistochemical staining and analysis of VEGFR2, S100A4, and S100A6 showed
      localization mainly in tumor cell cytoplasm. High VEGFR2 expression and low tumor
      category were independent variables associated with longer overall survival (OS)
      and disease-free survival, revealed by a bivariate Cox proportional hazards
      regression model (both P<0.001). In addition, the univariate log-rank test and
      the Cox model demonstrated that OS beyond 2 years was significantly greater among
      patients with low S100A6 expression than in those with high S100A6 expression (P
      = 0.017 and 0.022, respectively). Differences in tumor expression of S100A4 were
      not significantly associated with outcome. CONCLUSION: In this study, VEGFR2
      expression was significantly correlated with risk of disease relapse and OS in a
      defined cohort of patients with UC of the bladder treated by cystectomy.

PMID- 24880462
TI  - Neutrophil-lymphocyte ratio evaluation in patients undergoing radical cystectomy.

PMID- 24880458
TI  - CD80 and PD-L2 define functionally distinct memory B cell subsets that are
      independent of antibody isotype.
AB  - Memory B cells (MBCs) are long-lived sources of rapid, isotype-switched secondary
      antibody-forming cell (AFC) responses. Whether MBCs homogeneously retain the
      ability to self-renew and terminally differentiate or if these functions are
      compartmentalized into MBC subsets has remained unclear. It has been suggested
      that antibody isotype controls MBC differentiation upon restimulation. Here we
      demonstrate that subcategorizing MBCs on the basis of their expression of CD80
      and PD-L2, independently of isotype, identified MBC subsets with distinct
      functions upon rechallenge. CD80(+)PD-L2(+) MBCs differentiated rapidly into AFCs
      but did not generate germinal centers (GCs); conversely, CD80(-)PD-L2(-) MBCs
      generated few early AFCs but robustly seeded GCs. The gene-expression patterns of
      the subsets supported both the identity and function of these distinct MBC types.
      Hence, the differentiation and regeneration of MBCs are compartmentalized.

PMID- 24880463
TI  - The benefits of hypothermic machine perfusion are enhanced with Vasosol and alpha
      tocopherol in rodent donation after cardiac death livers.
AB  - The use of hypothermic machine perfusion (HMP) has recently been used to show an
      improvement in both standard and extended criteria donor liver grafts but
      creating a more dynamic preservation environment that can be supplemented with a
      variety of additives to aid in cold temperature metabolism and vasodilatation.
      Increasing the benefits of HMP, we explore the use of alpha-tocopherol in
      reducing inflammatory markers and apoptotic pathways to reduce the incidence of
      preservation injury. We explored the use of a donation after cardiac death (DCD)
      rodent model to test the additive benefits of alpha-tocopherol in HMP. The
      addition of alpha-tocopherol reduced the level of alanine aminotransferase (ALT)
      over the course of reperfusion as well, reduced the levels of inflammatory
      cytokines within a 90 minute reperfusion biopsy. Further benefit was seen with
      alpha-tocopherol through the reduction of the level of caspase 3/7 in the
      circulation, shown to be a result of the reduction of the levels of Cytochrome C
      mRNA. Liver perfusion with Vasosol(r) and HMP could benefit further from the
      addition of alpha-tocopherol to existing formulations of Vasosol(r). 

PMID- 24880460
TI  - Ontogeny of early life immunity.
AB  - The human immune system comprises cellular and molecular components designed to
      coordinately prevent infection while avoiding potentially harmful inflammation
      and autoimmunity. Immunity varies with age, reflecting unique age-dependent
      challenges including fetal gestation, the neonatal phase, and infancy. Here, we
      review novel mechanistic insights into early life immunity, with an emphasis on
      emerging models of human immune ontogeny, which may inform age-specific
      translational development of novel anti-infectives, immunomodulators, and
      vaccines. 

PMID- 24880464
TI  - Selective tumor cell killing by triptolide in p53 wild-type and p53 mutant
      ovarian carcinomas.
AB  - Triptolide is a traditional Chinese medicinal herb-derived antineoplastic agent.
      However, its antitumor activity against gynecologic carcinomas has not yet been
      well described. It is the purpose of this article to investigate the effect and
      mechanism of triptolide in human ovarian cancer using both A2780 (p53 wild) and
      OVCAR-3 (p53 mutated) cells. Our results showed that triptolide exerted a potent
      inhibitory effect on the growth and proliferation of both cell lines in a dose-
      and time-dependent manner and that the effect was independent of the expression
      of p53. In contrast, triptolide had only a marginal cytotoxicity in noncancerous
      ovary cells, lung fibroblast cells, and macrophage cells, indicating differential
      inhibitory effects of the drug on cell growth between ovarian cancer cells and
      normal tissue cells. Exposure of the ovarian cancer cells to triptolide induced
      apoptosis, as evaluated by annexin V/propidium iodide-labeled flow cytometry.
      Triptolide-induced apoptosis was accompanied by cytochrome c release and caspase
      3 activation and was associated with downregulation of Bcl-2 and upregulation of
      Bax. Cell cycle analysis demonstrated that treatment with triptolide induced cell
      cycle S phase arrest in A2780 cells and G2/M phase arrest in OVCAR-3 cells.
      Further detection by Western blotting revealed that the cell cycle arrest by
      triptolide in both cell lines occurred in concert with increased expression of
      p21(CIP1/WAF1). This study shows that triptolide selectively kills ovarian cancer
      cells with different p53 status predominantly through regulating the coordinate
      and dynamic cellular processes of proliferation and apoptosis, thereby making it
      a promising chemotherapeutic agent against a broad spectrum of ovarian
      carcinomas. 

PMID- 24880465
TI  - "Baby Heart Project": the Italian project for accreditation and quality
      management in pediatric cardiology and cardiac surgery.
AB  - Optimization of the relationship between the supply and the demand for medical
      services should ideally be taken into consideration for the planning within each
      national Health System. Although government national health organizations embrace
      this policy specifically, the contribution of expert committees (under the
      scientific societies' guarantee in any specific medical field) should be
      advocated for their capability to collect and analyze the data reported by the
      various national institutions. In addition, these committees have the competence
      to analyze the need for the resources necessary to the operation of these
      centers. The field of pediatric cardiology and cardiac surgery may represent a
      model of clinical governance of particular interest with regard to programming
      and to a definition of the quality standards that may be extended to highly
      specialized institutions and ideally to the entire Health System. The "Baby Heart
      Project," which represents a model of governance and clinical quality in the
      field of pediatric cardiology and cardiac surgery, was born from the spontaneous
      aggregation of a committee of experts, supported by duly appointed Italian
      Scientific Societies and guided by a national agency for accreditation. The
      ultimate aim is to standardize both procedures and results for future planning
      within the national Health System. 

PMID- 24880466
TI  - Novel and highly lethal NKX2.5 missense mutation in a family with sudden death
      and ventricular arrhythmia.
AB  - To date, several disease-related mutations in NKX2-5, a cardiac-specific homeobox
      gene, have been documented in patients with a variety of congenital heart
      diseases (CHDs). The most commonly reported phenotypes are secundum atrial septal
      defect (ASD) and atrioventricular conduction disease (AVCD). Reports of sudden
      cardiac death (SCD) have been attributed to progressive conduction disease
      preventable with pacemaker therapy. A retrospective chart review of individuals
      from three generations of a family with a novel NKX2-5 mutation associated with
      CHD, ventricular arrhythmias, and SCD despite pacemaker therapy was conducted.
      The review documented NKX2-5 Gln181His missense mutation in 11 phenotypically
      affected members of a single family with a strong family history of SCD, CHD, and
      AVCD. Before genotyping, four family members died suddenly, two despite pacemaker
      therapy. The ages at SCD were respectively 23, 29, 44, and 45 years. Observed
      phenotypic characteristics of genotype-positive patients included ASD,
      ventricular septal defect, aortic coarctation, tricuspid atresia,
      supraventricular tachycardia, progressive AVCD, and ventricular tachycardia
      documented on implantable cardiac defibrillator (ICD) recording. The age at
      presentation ranged from 5 months to 44 years, and AVCD was seen as early as
      infancy. Four phenotypically unaffected family members tested negative for the
      mutation. The findings of this review strongly suggest a new association of this
      NKX2-5 mutation with SCD from ventricular arrhythmia. This observation has
      significant implications for the choice of therapy for affected individuals,
      specifically the use of ICDs, and broadens the observed phenotypic spectrum of
      NKX2-5 mutations.

PMID- 24880467
TI  - Molecular screening for 22Q11.2 deletion syndrome in patients with congenital
      heart disease.
AB  - Few studies have investigated the prevalence of 22q11.2 deletion syndrome
      (22q11.2DS) among patients with isolated heart defects or nonconotruncal heart
      defects. Polymerase chain reaction (PCR) followed by length polymorphism
      restriction fragment analysis (RFLP) is useful for low-cost molecular diagnosis
      and screening. This cross-sectional study included 392 patients with congenital
      heart disease, described clinical features, and performed PCR-RFLP for analysis
      of polymorphism in three loci with a high heterozygosity rate located in the
      typically deleted region of 1.5 megabases. Heterozygosity excluded 22q11.2DS.
      Patients with homozygosity for the three markers underwent multiplex ligation
      dependent probe amplification (MLPA) and fluorescence in situ hybridization
      (FISH) for the final diagnosis, estimating the prevalence of 22q11.2DS. The use
      of PCR-RFLP excluded 22q11.2DS in 81.6 % (n = 320) of 392 patients. Of the
      remaining 72 patients, 65 underwent MLPA, showing 22q11.2DS in five cases
      (prevalence, 1.27 %). Four of these five patients underwent FISH, confirming the
      MLPA results. All five patients with the deletion had heart diseases commonly
      found with 22q11.2DS (interrupted aortic arch, persistent truncus arteriosus,
      tetralogy of Fallot, and ventricular septal defect plus atrial septal defect).
      Two patients had congenital extracardiac anomaly (one with arched palate and
      micrognathia and one with hypertelorism). Three patients reported recurrent
      respiratory infections, and one patient reported hypocalcemia. All were
      underweight or short in stature for their age. This study contributed to showing
      the prevalence of 22q11.2DS in patients with any congenital heart disease, with
      or without other features of the syndrome. Patients with 22q11.2DS may not have
      all the major features of the syndrome, and those that are found may be due to
      the heart defect.

PMID- 24880468
TI  - Black spotted larynx, a finding in patients addicted to inhalational opium.

PMID- 24880470
TI  - When is radiofrequency ablation not indicated in head and neck squamous cell
      carcinoma management?

PMID- 24880469
TI  - Human papilloma virus and survival of oropharyngeal cancer patients treated with
      surgery and adjuvant radiotherapy.
AB  - Impact of p16 protein, a surrogate marker for human papilloma virus induced
      cancer, p53 and EGFR as well as clinical factors on survival in a patient cohort
      with oropharyngeal squamous cell carcinoma (OPSCC) treated by surgical resection
      and adjuvant radiotherapy (RT) +/- concomitant chemotherapy (CT). This is a
      retrospective analysis of patient's charts and tumor tissue. 57 patients were
      consecutively included and their tumor tissue assembled on a tissue microarray
      following immunohistochemical analysis. Survival times were estimated by means of
      Kaplan-Meier analysis. The importance of clinical and immunohistochemical factors
      for outcome was estimated by cox proportional hazard models. With 88% 5-year
      overall survival, 91% 5-year disease-specific survival and 91% 5-year disease
      free survival, respectively, we found excellent survival rates in this surgically
      treated patient cohort of mainly advanced OPSCC (93% AJCC stage III or IV). The
      only factors positively influencing survival were p16 overexpression as well as
      p53 negativity and even more pronounced the combination of those biomarkers.
      Survival analysis of patients classified into three risk categories according to
      an algorithm based on p16, smoking, T- and N-category revealed a low,
      intermediate and high-risk group with significant survival differences between
      the low and the high-risk group. Patients with OPSCC can be successfully treated
      by surgery and adjuvant RT +/- CT with a clear survival benefit of p16 positive,
      p53 negative patients. We recommend considering a combination of
      immunohistochemical (p16, p53) and clinical factors (smoking, T- and N-category)
      for risk stratification.

PMID- 24880471
TI  - Expression of podoplanin and prognosis in oropharyngeal cancer.
AB  - It has been shown that podoplanin expression is associated with carcinoma of the
      aerodigestive tract. Recent studies indicate that podoplanin may serve as a
      prognostic biomarker in oral carcinoma. In order to provide evidence on the role
      of podoplanin in oropharyngeal squamous cell carcinoma, we evaluated the
      prognostic impact of podoplanin in these patients. We analyzed formalin-fixed
      tissue samples from 107 consecutive patients with oropharyngeal squamous cell
      carcinoma. HPV typing and immunohistochemical staining for both p16 and
      podoplanin were performed. Expression of podoplanin was seen in 38.3% of all
      cases. We found no correlation of the podoplanin scores with either p16
      expression or with HPV status. There was no significant correlation of podoplanin
      expression with the staging variables T, N, M, and tumor grading. Podoplanin
      expression did neither influence the 5-year overall survival nor the 5-year
      disease-free survival. Concluding, we could not find a prognostic role of
      podoplanin expression neither in the HPV-positive cases nor in the HPV-negative
      cases. It appears that podoplanin is not expressed as often in oropharyngeal
      cancer compared to oral cancer. We could not show any relation of lymph node
      metastases and podoplanin expression in this homogenous cohort of tumors.

PMID- 24880472
TI  - Surgical management of recurrent sinonasal mucosal melanoma: endoscopic or
      transfacial resection.
AB  - Sinonasal mucosal melanoma (SNMM) is associated with poor prognosis. Local
      recurrence is common and represents a major problem in the therapy. Wide
      resection surgery is usually applied. However, given the almost futile prognosis,
      optimal symptom control may be preferable to wide resection at all costs. The aim
      of our study was to analyze the outcome in patients with recurrent SNMM treated
      by transfacial radical surgery or by a less invasive endoscopically controlled
      approach. Patients with recurrent grade III or IV staged SNMM who presented to
      our ENT department between 2000 and 2010 were either treated by transfacial (n =
      10) or endoscopically controlled surgery (n = 12). The patients' charts were
      reviewed for clinical symptoms, relapse-free time and survival time. Clinical
      symptoms improved after surgery. The morbidity after endoscopic surgery was
      significantly lower than after transfacial surgery. The chosen surgical technique
      did neither affect relapse-free nor survival time. When treating recurrent SNMM,
      the comparatively gentle and less mutilating endoscopic approach proved to be a
      sufficient surgical procedure, being not inferior to aggressive surgery with
      respect to recurrence and survival rate.

PMID- 24880473
TI  - First detection of Kemerovo virus in Ixodes pavlovskyi and Ixodes persulcatus
      ticks collected in Novosibirsk region, Russia.
AB  - Kemerovo group viruses are tick-transmitted members of Orbivirus genus of the
      Reoviridae family that can cause infections of the central nervous system of
      humans. In this work, Kemerovo virus (KEMV) RNA was detected for the first time
      in Novosibirsk region of Western Siberia, Russia, in Ixodes pavlovskyi and Ixodes
      persulcatus ticks. 

PMID- 24880474
TI  - Analysis on the association between PPARalpha/gamma polymorphisms and
      lipoprotein(a) in a Chinese Han population.
AB  - Lipoprotein(a) [Lp(a)], a low-density lipoprotein-like particle, is recognized as
      an independent risk factor for atherosclerosis, cardiovascular diseases, and
      diabetic vascular diseases. Our recent studies revealed that the single
      nucleotide polymorphisms (SNPs) of peroxisome proliferator-activated receptors
      (PPARalpha/delta/gamma) gene are involved in the regulation of lipid storage and
      metabolism. In order to investigate the relationships between the SNPs of
      PPARalpha/gamma gene and plasma levels of Lp(a), 644 participants were randomly
      selected from Chinese Han population in the present study. As the results shown,
      Lp(a) was significantly associated with L162V (rs1800206) in PPARalpha. Compared
      with those subjects with widetype (LL), significantly higher Lp(a) concentration
      was determined in the individuals with mutant (LV + VV) (mean difference: 49.07
      mg/l, 95% CI 23.32-74.82 mg/l, p = 0.0002). Moreover, with generalized
      multifactor dimensionality reduction analysis, our present results indicated that
      there was a significant association between plasma Lp(a) level and gene-gene
      interaction among the polymorphisms rs1800206, rs135539 in PPARalpha and
      rs10865710, rs1805192, and rs4684847 in PPARgamma. Therefore, our presented study
      indicated that PPARalpha/gamma polymorphisms should be involved in the regulation
      of plasma Lp(a) in independently and/or in an interactive manner, suggesting that
      PPARalpha/gamma gene may influence the risk of hypertension, cardiovascular
      diseases, and dyslipidemia by regulating Lp(a) level.

PMID- 24880475
TI  - Overexpression of a tea flavanone 3-hydroxylase gene confers tolerance to salt
      stress and Alternaria solani in transgenic tobacco.
AB  - Flavan-3-ols are the major flavonoids present in tea (Camellia sinensis) leaves.
      These are known to have antioxidant and free radical scavenging properties in
      vitro. Flavanone 3-hydroxylase is considered to be an important enzyme of
      flavonoid pathway leading to accumulation of flavan-3-ols in tea. Expression
      analysis revealed the upregulation in transcript levels of C. sinensis flavanone
      3-hydroxylase (CsF3H) encoding gene under salt stress. In this study, the
      biotechnological potential of CsF3H was evaluated by gene overexpression in
      tobacco (Nicotiana tabacum cv. Xanthi). Overexpression of CsF3H cDNA increased
      the content of flavan-3-ols in tobacco and conferred tolerance to salt stress and
      fungus Alternaria solani infection. Transgenic tobaccos were observed for
      increase in primary root length, number of lateral roots, chlorophyll content,
      antioxidant enzyme expression and their activities. Also, they showed lesser
      malondialdehyde content and electrolyte leakage compared to control tobacco
      plants. Further, transgenic plants produced higher degree of pectin methyl
      esterification via decreasing pectin methyl esterase (PME) activity in roots and
      leaves under unstressed and salt stressed conditions. The effect of flavan-3-ols
      on pectin methyl esterification under salt stressed conditions was further
      validated through in vitro experiments in which non-transgenic (wild) tobacco
      seedlings were exposed to salt stress in presence of flavan-3-ols, epicatechin
      and epigallocatechin. The in vitro exposed seedlings showed similar trend of
      increase in pectin methyl esterification through decreasing PME activity as
      observed in CsF3H transgenic lines. Taken together, overexpression of CsF3H
      provided tolerance to salt stress and fungus A. solani infection to transgenic
      tobacco through improved antioxidant system and enhanced pectin methyl
      esterification. 

PMID- 24880477
TI  - Sternalock plating system for elderly post-sternotomy patients.

PMID- 24880476
TI  - Sequence comparison and phylogenetic analysis by the Maximum Likelihood method of
      ribosome-inactivating proteins from angiosperms.
AB  - Ribosome-inactivating proteins (RIPs) from angiosperms are rRNA N-glycosidases
      that have been proposed as defence proteins against virus and fungi. They have
      been classified as type 1 RIPs, consisting of single-chain proteins, and type 2
      RIPs, consisting of an A chain with RIP properties covalently linked to a B chain
      with lectin properties. In this work we have carried out a broad search of RIP
      sequence data banks from angiosperms in order to study their main structural
      characteristics and phylogenetic evolution. The comparison of the sequences
      revealed the presence, outside of the active site, of a novel structure that
      might be involved in the internal protein dynamics linked to enzyme catalysis.
      Also the B-chains presented another conserved structure that might function
      either supporting the beta-trefoil structure or in the communication between both
      sugar-binding sites. A systematic phylogenetic analysis of RIP sequences revealed
      that the most primitive type 1 RIPs were similar to that of the actual monocots
      (Poaceae and Asparagaceae). The primitive RIPs evolved to the dicot type 1
      related RIPs (like those from Caryophyllales, Lamiales and Euphorbiales). The
      gene of a type 1 RIP related with the actual Euphorbiaceae type 1 RIPs fused with
      a double beta trefoil lectin gene similar to the actual Cucurbitaceae lectins to
      generate the type 2 RIPs and finally this gene underwent deletions rendering
      either type 1 RIPs (like those from Cucurbitaceae, Rosaceae and Iridaceae) or
      lectins without A chain (like those from Adoxaceae). 

PMID- 24880478
TI  - Short-term ventricular assist device in post-cardiotomy cardiogenic shock:
      factors influencing survival.
AB  - Post-cardiotomy cardiogenic shock (PCCS) results in substantial morbidity and
      mortality, whereas refractory cases require mechanical circulatory support. The
      aim of this study was to evaluate factors influencing survival during short-term
      ventricular assist support in PCCS. In total, 154 CentriMag((r)) (Thoratec; CA,
      USA) devices were implanted for cardiogenic shock between 2004 and 2011 out of
      which 31 were for PCCS. A retrospective review was performed in 31 PCCS patients
      who required the CentriMag short-term VAD as a bridge to decision. Survivors and
      non-survivors were compared with respect to pre- and intra-operative
      characteristics as well as duration of short-term VAD support. Mean duration of
      support was 11.7 +/- 15.4 days (range 1-65 days). Seventeen (54.83 %) patients
      died on support, 14 (45.16 %) were weaned off or upgraded to long-term device,
      while 11 (35.5 %) were discharged home. The overall survival to myocardial
      recovery and device explantation, or upgrade to a long-term VAD, was 41.9 % (n =
      13) at the study cutoff. EuroSCORE II was significantly higher in non-survivors
      as compared to survivors (p = 0.047). The duration of short-term VAD support was
      significantly longer in survivors (p < 0.001). The CentriMag is a versatile, safe
      and effective short-term circulatory support for patients with PCCS as a bridge
      to decision which enables longer support and better recovery of both heart and
      end-organ function and thus may improve the survival of PCCS patients. Lower
      EuroSCORE may be essential for myocardial recovery in PCCS. 

PMID- 24880479
TI  - All atrial septal defects should be closed.

PMID- 24880480
TI  - Predictors of permanent pacemaker requirement after transcatheter aortic valve
      implantation: insights from a Brazilian registry.
AB  - BACKGROUND: The aim of this study is to evaluate the predictors of permanent
      pacemaker (PPM) implantation after TAVI. METHODS: Between January 2008 and
      February 2012, 418 patients with severe aortic stenosis underwent TAVI and were
      enrolled in a Brazilian multicenter registry. After excluding patients who died
      during the procedure and those with a previous PPM, 353 patients were included in
      the analysis. RESULTS: At 30 days, the overall incidence of PPM implantation was
      25.2%. Patients requiring PPM were more likely to be older (82.73 vs. 81.10
      years, p=0.07), have pre-dilation (68.42% vs. 60.07%, p=0.15), receive CoreValve
      (93.68% vs. 82.55%, p=0.008), and have baseline right bundle branch block (RBBB,
      25.26% vs. 6.58%, p<0.001). On multivariable analysis, CoreValve vs. Sapien XT
      (OR, 4.24; 95% CI, 1.56-11.49; p=0.005), baseline RBBB (OR, 4.41; 95% CI, 2.20
      8.82; p<0.001), and balloon pre-dilatation (OR, 1.75; 95% CI, 1.02-3.02; p=0.04)
      were independent predictors of PPM implantation. CONCLUSION: PPM implantation
      occurred in approximately one-fourth of cases. Pre-existing RBBB, balloon pre
      dilatation, and CoreValve use were independent predictors of PPM after TAVI. The
      type of prosthesis used and pre-balloon dilatation should be considered in TAVI
      candidates with baseline RBBB.

PMID- 24880481
TI  - Ferric carboxymaltose improves exercise capacity and quality of life in patients
      with pulmonary arterial hypertension and iron deficiency: a pilot study.
AB  - BACKGROUND: Pulmonary arterial hypertension (PAH) is a progressive condition
      harboring a poor prognosis. Iron deficiency in PAH correlates with disease
      severity and mortality. While replacement therapy may be beneficial, dietary iron
      absorption is impaired in PAH patients by hepcidin, a key regulatory protein of
      iron homoeostasis. We therefore assessed the therapeutic potential and safety of
      intravenous iron supplementation in patients with PAH and iron deficiency.
      METHODS: 20 patients with PAH and iron deficiency, who were on stable targeted
      PAH therapy, received a single infusion of <=1000 mg ferric carboxymaltose. All
      patients were assessed at baseline and two months after iron treatment. Exercise
      capacity was evaluated based on the 6-minute-walking distance (6MWD), and quality
      of life (QoL) was assessed by the SF-36 questionnaire (100 point scale). The
      effects were compared to 20 matched patients with stable PAH without iron
      deficiency who did not receive ferric carboxymaltose. RESULTS: In iron deficient
      patients, iron supplementation led to a marked improvement of iron status (serum
      iron 5.7+/-0.4 to 11.1+/-1.1 MUmol/L, ferritin 29.3+/-6.3 to 145.2+/-25.4 MUg/L,
      transferrin saturation 7.5+/-0.7 to 19.3+/-2.3%, all p<=0.001). Iron-deficient
      patients receiving ferric carboxymaltose showed a significant increase of the
      6MWD from 346.5+/-28.3 to 374.0+/-25.5 m (p=0.007), whereas no significant
      changes were found in the control group not receiving iron supplementation (6MWD
      389.9+/-25.3 to 379.6+/-26.2 m; n.s.), resulting in a net increase in the 6MWD of
      37.8m (p=0.003). This was associated with an improvement in QoL (SF-36 score from
      44.3+/-3.7 to 50.6+/-3.6; p=0.01). Only minimal side-effects were reported.
      CONCLUSIONS: These data indicate that parenteral iron supplementation with ferric
      carboxymaltose significantly improves exercise capacity and QoL and is well
      tolerated in patients with PAH and iron deficiency, and when administered in
      addition to targeted PAH therapies. Our results provide proof of concept for
      further studies evaluating the potential of iron as an adjunct in PAH treatment
      on a larger scale.

PMID- 24880482
TI  - Effect of troxerutin on insulin signaling molecules in the gastrocnemius muscle
      of high fat and sucrose-induced type-2 diabetic adult male rat.
AB  - Troxerutin is a trihydroxyethylated derivative of the flavonoid, rutin. It has
      been reported to possess the hepatoprotective, nephroprotective, antioxidant,
      anti-inflammatory, and antihyperlipidemic activities. Troxerutin treatment
      reduced the blood glucose and glycosylated hemoglobin levels in high-cholesterol
      induced insulin-resistant mice and in type-2 diabetic patients. However, the
      mechanism by which it exhibits antidiabetic property was unknown. Therefore, the
      present study was designed to evaluate the effect of troxerutin on insulin
      signaling molecules in gastrocnemius muscle of high fat and sucrose-induced type
      2 diabetic rats. Wistar male albino rats were selected and divided into five
      groups. Group I: Control. Group II: High fat and sucrose-induced type-2 diabetic
      rats. Group III: Type-2 diabetic rats treated with troxerutin (150 mg/kg body
      weight/day orally). Group IV: Type-2 diabetic rats treated with metformin (50
      mg/kg body weight/day orally). Group V: Normal rats treated with troxerutin (150
      mg/kg body weight/day orally). After 30 days of treatment, fasting blood glucose,
      oral glucose tolerance, serum lipid profile, and the levels of insulin signaling
      molecules, glycogen, glucose uptake, and oxidation in gastrocnemius muscle were
      assessed. Diabetic rats showed impairment in insulin signaling molecules (IR, p
      IRS-1(Tyr632), p-Akt(Ser473), beta-arrestin-2, c-Src, p-AS160(Thr642), and GLUT4
      proteins), glycogen concentration, glucose uptake, and oxidation. Oral
      administration of troxerutin showed near normal levels of blood glucose, serum
      insulin, lipid profile, and insulin signaling molecules as well as GLUT4 proteins
      in type-2 diabetic rats. It is concluded from the present study that troxerutin
      may play a significant role in the management of type-2 diabetes mellitus, by
      improving the insulin signaling molecules and glucose utilization in the skeletal
      muscle. 

PMID- 24880483
TI  - miR-1246 releases RTKN2-dependent resistance to UVB-induced apoptosis in HaCaT
      cells.
AB  - MicroRNAs are a kind of small non-coding RNAs that play important roles in
      various biological processes such as cell proliferation, differentiation, and
      apoptosis. Cellular responses to UV-induced apoptosis have been suggested to be
      regulated by microRNAs at the posttranscriptional level, while the detailed
      mechanisms underlying this process remain unclear. Our aim in this study was to
      investigate the effects of miR-1246 in UVB-induced apoptosis and to identify the
      functional targets of miR-1246 in keratinocyte HaCaT cells. The expression of miR
      1246 and apoptotic genes in HaCaT cells experiencing UVB stress was determined
      using quantitative real-time PCR. miR-1246 functions in UVB-induced apoptosis
      were quantified via fluorescence-activated cell sorter analysis of miR-1246 mimic
      or inhibitor-transfected cells. Additionally, the regulatory relationship between
      RTKN2 and miR-1246 was identified by Western blot and luciferase reporter assays.
      miR-1246 was upregulated accompanying with UVB-irradiated apoptosis in HaCaT
      cells. Overexpression of miR-1246 promoted UVB-induced apoptosis, while knockdown
      of miR-1246, using a specific inhibitor, resulted in a significant reduction in
      UVB-elicited apoptosis. We further demonstrate that miR-1246 negatively regulated
      the expression of RTKN2 through binding to the 3'-untranslated region of RTKN2 at
      the posttranscriptional level. Moreover, RTKN2 was observed to be resistant to
      UVB-induced apoptosis and RTKN2 antagonized the pro-apoptotic effects of miR-1246
      during UVB-induced apoptosis in HaCaT cells. These findings suggested that miR
      1246 promotes UVB-induced apoptosis by downregulating RTKN2 expression and that
      UVB-upregulated miR-1246 released RTKN2-dependent resistance to UVB-induced
      apoptosis by targeting RTKN2 post-transcriptionally in keratinocyte cells. 

PMID- 24880484
TI  - Gene expression profiling of endometrium versus bone marrow-derived mesenchymal
      stem cells: upregulation of cytokine genes.
AB  - Postulated Stem/progenitor cells involved in endometrium regeneration are
      epithelial, mesenchymal, and endothelial. Bone marrow (BM) has been implicated in
      endometrial stem cells. We aimed at studying gene expression profiling of
      endometrial mesenchymal stem cells compared to BM MSCS to better understand their
      nature and functional phenotype. Endometrial tissues were obtained from
      premenopausal hysterectomies (n = 3), minced and enzymatically digested as well
      as Normal BM aspirates (n=3). Immunophenotyping, differentiation to mesoderm, and
      proliferation were studied. The expression profile of 84 genes relevant to
      mesenchymal stem cells was performed. Fold change calculations were determined
      with SA Biosciences data analysis software. VEGF, G-CSF, and GM-CSF in cultures
      supernatants of MSCs were assayed by Luminex immunoassay. Endo MSCs possess
      properties similar to BM MSCs. Cumulative population doubling was significantly
      higher in Endo MSCs compared to BM MSCs (p < 0.001). 52 core genes were shared
      between both generated MSCs including stemness, self-renewal, members of the
      Notch, TGFB, FGF, and WNT.16 downregulated genes (VCAM, IGF1)and 16 upregulated
      in Endo MSCs compared to BM (p < 0.05 -> fourfolds). They included mostly
      cytokine and growth factor genes G-CSF, GM-CSF, VWF, IL1b, GDF15, and KDR. VEGF
      and G-CSF levels were higher in Endo MSCs supernatants (p < 0.0001). Cells
      sharing MSC and endothelial cell characteristics could be isolated from the human
      endometrium. Endo MSCs share a core genetic profile with BM MSCs including
      stemness. They show upregulation of genes involved in vasculogenesis,
      angiogenesis, cell adhesion, growth proliferation, migration, and differentiation
      of endothelial cells, all contributing to endometrial function. 

PMID- 24880485
TI  - Carvacrol modulates instability of xenobiotic metabolizing enzymes and
      downregulates the expressions of PCNA, MMP-2, and MMP-9 during diethylnitrosamine
      induced hepatocarcinogenesis in rats.
AB  - Hepatocellular carcinoma is the fifth most common malignant tumor in the world,
      both in terms of incidence and mortality in Asian and Western countries. There
      are currently limited therapeutic regimens available for effective treatment of
      this cancer. Carvacrol is a predominant monoterpenoic phenol believed to impede
      cancer promotion and progression. The present study was conducted to decipher the
      role of carvacrol during diethylnitrosamine (DEN)-induced hepatocarcinogenesis in
      male wistar albino rats. Carvacrol (15 mg/kg body weight) suppressed the
      elevation of serum tumor marker enzymes, carcinoembryonic antigen, and alpha-feto
      protein induced by DEN. The activities of phase I enzymes increased markedly
      during DEN induction, but was found to be significantly lowered upon carvacrol
      treatment. On the contrary, the phase II enzymes decreased in DEN-administered
      animals, which was improved normalcy upon carvacrol-treated animals. DEN
      administered animals showed increased mast cell counts, argyrophilic nucleolar
      organizing regions, proliferating cell nuclear antigen, and matrix
      metalloproteinases (MMPs-2/9), whereas carvacrol supplementation considerably
      suppressed all the above abnormalities. The results suggest that the carvacrol
      exhibited the potential anticancer activity by inhibiting cell proliferation and
      preventing metastasis in DEN-induced hepatocellular carcinogenesis. 

PMID- 24880486
TI  - Comparison of adjacent segment disease after minimally invasive or open
      transforaminal lumbar interbody fusion.
AB  - Adjacent segment disease (ASD) is a potential long-term risk after lumbar fusion.
      Its incidence has been evaluated in anterior and posterior lumbar interbody
      fusions, but few studies have focused on transforaminal lumbar interbody fusion
      (TLIF). Relative risk of ASD with open or minimally invasive (MI) TLIF is poorly
      understood. To report our experience with risk for ASD in patients receiving TLIF
      and test its association with surgical approach, we performed a retrospective
      cohort study based on medical record review at a single institution. Eligible
      patients were ? 18 years old at operation, underwent single-level TLIF during the
      period 2007-2008, and had at least 6 months postoperative follow-up. Patients
      were categorized by surgical approach (open versus MI). Primary outcome of
      interest was development of symptomatic ASD, defined by (1) new back and/or leg
      pain, (2) imaging findings adjacent to original surgical level, and (3) decision
      to treat. A total of 68 patients (16 open, 52 MI) were included in the analysis.
      Groups had similar baseline characteristics, except the open group tended to be
      older (p=0.04). Seven (10%) patients developed ASD. Mean patient age was 62 years
      and three were male. Three underwent open and four underwent MI TLIF. Risk of ASD
      did not differ significantly by surgical approach. The MI group showed a trend
      toward decreased risk of ASD compared to the open group, although it was not
      statistically significant. This suggests MI TLIF may be associated with decreased
      long-term morbidity compared to the open approach. Large prospective studies are
      needed to confirm these findings.

PMID- 24880488
TI  - Genome editing in the human malaria parasite Plasmodium falciparum using the
      CRISPR-Cas9 system.
AB  - Genome manipulation in the malaria parasite Plasmodium falciparum remains largely
      intractable and improved genomic tools are needed to further understand
      pathogenesis and drug resistance. We demonstrated the CRISPR-Cas9 system for use
      in P. falciparum by disrupting chromosomal loci and generating marker-free,
      single-nucleotide substitutions with high efficiency. Additionally, an
      artemisinin-resistant strain was generated by introducing a previously implicated
      polymorphism, thus illustrating the value of efficient genome editing in malaria
      research. 

PMID- 24880489
TI  - Novel synthesis of dihydropyrimidines for alpha-glucosidase inhibition to treat
      type 2 diabetes: in vitro biological evaluation and in silico docking.
AB  - A convenient and efficient new method has been established for the synthesis of
      dihydropyrimidines by inexpensive and non-toxic N-acetyl glycine (NAG) catalysed
      reaction of aromatic aldehydes with ethyl acetoacetate and urea/thiourea. This
      method is applicable for various substituted aldehydes as well as urea and
      thiourea. It has also been used to synthesize bicyclic oxygen-bridged pyrimidine
      derivatives (4d, 4j). The biological assay revealed that the majority of
      compounds synthesized displayed modest inhibitory activity against alpha
      glucosidase at low micro-molar concentrations. Molecular docking studies were
      also performed on the most active compound, 4f (with IC50 value 112.21+/-0.97
      MUM), to show the enzyme - inhibitor interactions.

PMID- 24880490
TI  - Collection of gender identity data using electronic medical records: survey of
      current end-user practices.

PMID- 24880491
TI  - Identification of scanner models by comparison of scanned hologram images.
AB  - A method to identify scanner models that had been used to forge low-level
      counterfeit currencies was proposed in this study. The method identified a
      scanner model by characterizing differences between hologram images that exist in
      low-level counterfeit currencies. Twenty scanners of 18 different models were
      used to make samples of hologram images used in this study. The method was
      divided into two steps: identification of capturing conditions and identification
      of the scanner model. The first proposed protocol used correlations of spatial
      distribution of brightness to identify capturing conditions. A second proposed
      protocol used correlations of color distributions to identify a scanner model.
      The effectiveness of the protocols was demonstrated with numerical methods and
      sample images. The preliminary study revealed that it is necessary to consider
      the orientation of the holograms when the scanner models were identified, but 180
      degrees  rotations can be ignored. Moreover, it is necessary to consider position
      in the main scanning direction of the bed for charged-coupled-device scanners.
      The demonstration showed that the first protocol could correctly identify the
      capturing conditions of almost all hologram images. However, one image could not
      be identified correctly; the protocol could distinguish images captured by
      charged-coupled-device scanners and those captured by contact image sensor
      scanners if the hologram was placed on the right or left edge of the scanner bed,
      but could not distinguish them if the hologram was placed on the inside. The
      demonstration also showed that the second protocol could correctly identify
      scanner models of all hologram images. 

PMID- 24880492
TI  - Investigating letter recognition in the brain by varying typeface: an event
      related potential study.
AB  - We aimed to investigate the contributions of visual letter form and abstract
      letter identity to the time course of letter recognition, by manipulating the
      typeface (i.e. font) in which letters were presented. Twenty-six adult
      participants completed a modified one-back task, where letters where presented in
      easy-to-read typefaces ("fluent" letter stimuli) or difficult-to-read typefaces
      ("disfluent" letter stimuli). Task instructions necessitated that participant's
      focus on letter identity not visual letter form. Electroencephalography was
      collected and event-related potentials (ERPs) were calculated relative to letter
      stimuli. It was found that typeface affected both early-mid (N1 amplitude and P2
      N2 amplitude and latency) and late processing (450-600ms), thereby including time
      points whereby it is theorised that abstract identity is extracted from visual
      letter form (that is, 300ms post-stimulus). Visual features of the letter
      therefore affect its processing well beyond the currently theorised point at
      which abstract information is extracted; which could be explained by a feedback
      loop between abstract letter representations and lower-level visual form
      processing units, which is not included in current cognitive reading models. 

PMID- 24880494
TI  - Axial QCT: clinical applications and new developments.
AB  - Quantitative computed tomography (QCT) is currently undergoing a renaissance,
      with an increasing number of studies being published and the definition of both
      QCT-specific osteoporosis thresholds and treatment criteria. Compared with dual
      energy X-ray absorptiometry, the current standard bone mineral density technique,
      QCT has a number of pertinent advantages, including volumetric measurements, less
      susceptibility to degenerative spine changes, and higher sensitivity to changes
      in bone mass. Disadvantages include the higher radiation doses and less
      experience with fracture prediction and therapy monitoring. Over the last 10 yr,
      a number of novel applications have been described allowing assessment of bone
      mineral density and bone quality in larger patient populations, developments that
      may substantially improve patient care.

PMID- 24880495
TI  - Comparison of femoral neck BMD evaluation obtained using Lunar DXA and QCT with
      asynchronous calibration from CT colonography.
AB  - For patients undergoing screening computed tomography colonography (CTC), an
      opportunity exists for bone mineral density (BMD) screening without additional
      radiation exposure using quantitative computed tomography (QCT). This study
      investigated the use of dual-energy X-ray absorptiometry (DXA)-equivalent QCT
      Computed Tomography X-Ray Absorptiometry (CTXA) analysis at the hip obtained
      using CTC examinations using a retrospective asynchronous calibration of patient
      scans. A cohort of 33 women, age 61.3 (10.6) yr (mean [standard deviation]), had
      routine CTC using various GE LightSpeed CT scanner models followed after 0-9 mo
      by a DXA hip BMD examination using a GE Lunar Prodigy machine. Areal bone mineral
      density (aBMD) and T-scores of the proximal femur were measured from either prone
      or supine CTC examinations using Mindways QCT Pro software following standard
      workflow except that the CT scanners were asynchronously calibrated by phantoms
      scanned retrospectively of the CTC examination without the subject present. CTXA
      and DXA aBMD were highly correlated (R2=0.907) with a linear relationship of
      DXA_BMD=1.297*CTXA_BMD+0.048. The standard error of estimate (SEE) on the linear
      fit was 0.053 g/cm2. CTXA and DXA T-scores showed a linear relationship of DXA_T
      score=1.034*CTXA_T-score+0.3 and an SEE of 0.379 T-scores. CTXA and DXA aBMD and
      T-score measurements showed good correlation despite asynchronous scan
      acquisition and retrospective QCT calibration. The SEE of 0.053 g/cm2 is on par
      with the literature comparing Hologic and Lunar DXA devices. The observed
      relationship between CTXA and Lunar DXA aBMD matches predictions from published
      cross-calibrations relating CTXA to DXA aBMD measurement. Thus, opportunistic use
      of CTXA T-scores obtained at the time of CTC could enhance osteoporosis
      screening.

PMID- 24880493
TI  - Sulforaphane reduces vascular inflammation in mice and prevents TNF-alpha-induced
      monocyte adhesion to primary endothelial cells through interfering with the NF
      kappaB pathway.
AB  - Sulforaphane, a naturally occurring isothiocyanate present in cruciferous
      vegetables, has received wide attention for its potential to improve vascular
      function in vitro. However, its effect in vivo and the molecular mechanism of
      sulforaphane at physiological concentrations remain unclear. Here, we report that
      a sulforaphane concentration as low as 0.5 MUM significantly inhibited tumor
      necrosis factor-alpha (TNF-alpha)-induced adhesion of monocytes to human
      umbilical vein endothelial cells, a key event in the pathogenesis of
      atherosclerosis both in static and under flow conditions. Such physiological
      concentrations of sulforaphane also significantly suppressed TNF-alpha-induced
      production of monocyte chemotactic protein-1 and adhesion molecules including
      soluble vascular adhesion molecule-1 and soluble E-selectin, key mediators in the
      regulation of enhanced endothelial cell-monocyte interaction. Furthermore,
      sulforaphane inhibited TNF-alpha-induced nuclear factor (NF)-kappaB
      transcriptional activity, Inhibitor of NF-kappaB alpha (IkappaBalpha) degradation
      and subsequent NF-kappaB p65 nuclear translocation in endothelial cells,
      suggesting that sulforaphane can inhibit inflammation by suppressing NF-kappaB
      signaling. In an animal study, sulforaphane (300 ppm) in a mouse diet
      significantly abolished TNF-alpha-increased ex vivo monocyte adhesion and
      circulating adhesion molecules and chemokines in C57BL/6 mice. Histology showed
      that sulforaphane treatment significantly prevented the eruption of endothelial
      lining in the intima layer of the aorta and preserved elastin fibers' delicate
      organization, as shown by Verhoeff-van Gieson staining. Immunohistochemistry
      studies showed that sulforaphane treatment also reduced vascular adhesion
      molecule-1 and monocyte-derived F4/80-positive macrophages in the aorta of TNF
      alpha-treated mice. In conclusion, sulforaphane at physiological concentrations
      protects against TNF-alpha-induced vascular endothelial inflammation, in both in
      vitro and in vivo models. This anti-inflammatory effect of sulforaphane may be,
      at least in part, associated with interfering with the NF-kappaB pathway. 

PMID- 24880496
TI  - ISCD in 2014: state of the society.

PMID- 24880487
TI  - A community effort to assess and improve drug sensitivity prediction algorithms.
AB  - Predicting the best treatment strategy from genomic information is a core goal of
      precision medicine. Here we focus on predicting drug response based on a cohort
      of genomic, epigenomic and proteomic profiling data sets measured in human breast
      cancer cell lines. Through a collaborative effort between the National Cancer
      Institute (NCI) and the Dialogue on Reverse Engineering Assessment and Methods
      (DREAM) project, we analyzed a total of 44 drug sensitivity prediction
      algorithms. The top-performing approaches modeled nonlinear relationships and
      incorporated biological pathway information. We found that gene expression
      microarrays consistently provided the best predictive power of the individual
      profiling data sets; however, performance was increased by including multiple,
      independent data sets. We discuss the innovations underlying the top-performing
      methodology, Bayesian multitask MKL, and we provide detailed descriptions of all
      methods. This study establishes benchmarks for drug sensitivity prediction and
      identifies approaches that can be leveraged for the development of new methods. 

PMID- 24880497
TI  - Vitamin D status is associated with bone mineral density and bone mineral content
      in preschool-aged children.
AB  - This study examined the associations between vitamin D status, bone mineral
      content (BMC), areal bone mineral density (aBMD), and markers of calcium
      homeostasis in preschool-aged children. Children (n=488; age range: 1.8-6.0 y)
      were randomly recruited from Montreal. The distal forearm was scanned using a
      peripheral dual-energy X-ray absorptiometry scanner (Lunar PIXI; GE Healthcare,
      Fairfield, CT). A subset (n=81) had clinical dual-energy X-ray absorptiometry
      (cDXA) scans (Hologic 4500A Discovery Series) of lumbar spine (LS) 1-4, whole
      body, and ultradistal forearm. All were assessed for plasma 25-hydroxyvitamin D
      [25(OH)D] and parathyroid hormone concentrations (Liaison; Diasorin), ionized
      calcium (ABL80 FLEX; Radiometer Medical A/S), and dietary vitamin D and calcium
      intakes by survey. Age (p<0.001) and weight-for-age Z-score (p<0.001) were
      positively associated with BMC and aBMD in all regression models, whereas male
      sex contributed positively to forearm BMC and aBMD. Having a 25(OH)D
      concentration of >75 nmol/L positively associated with forearm and whole body BMC
      and aBMD (p<0.036). Sun index related to (p<0.029) cDXA forearm and LS 1-4 BMC
      and whole-body aBMD. Nutrient intakes did not relate to BMC or aBMD. In
      conclusion, higher vitamin D status is linked to higher BMC and aBMD of forearm
      and whole body in preschool-aged children.

PMID- 24880498
TI  - The effects of positive and negative parenting practices on adolescent mental
      health outcomes in a multicultural sample of rural youth.
AB  - The quality of parent-child relationships has a significant impact on adolescent
      developmental outcomes, especially mental health. Given the lack of research on
      rural adolescent mental health in general and rural parent-child relationships in
      particular, the current longitudinal study explores how rural adolescents' (N =
      2,617) perceptions of parenting practices effect their mental health (i.e.,
      anxiety, depression, aggression, self-esteem, future optimism, and school
      satisfaction) over a 1 year period. Regression models showed that current
      parenting practices (i.e., in Year 2) were strongly associated with current
      adolescent mental health outcomes. Negative current parenting, manifesting in
      parent-adolescent conflict, was related to higher adolescent anxiety, depression,
      and aggression and lower self-esteem, and school satisfaction. Past parent
      adolescent conflict (i.e., in Year 1) also positively predicted adolescent
      aggression in the present. Current positive parenting (i.e., parent support,
      parent-child future orientation, and parent education support) was significantly
      associated with less depression and higher self-esteem, future optimism, and
      school satisfaction. Past parent education support was also related to current
      adolescent future optimism. Implications for practice and limitations were
      discussed.

PMID- 24880499
TI  - Synthesis of milligram quantities of proteins using a reconstituted in vitro
      protein synthesis system.
AB  - In this study, the amount of protein synthesized using an in vitro protein
      synthesis system composed of only highly purified components (the PURE system)
      was optimized. By varying the concentrations of each system component, we
      determined the component concentrations that result in the synthesis of 0.38
      mg/mL green fluorescent protein (GFP) in batch mode and 3.8 mg/mL GFP in dialysis
      mode. In dialysis mode, protein concentrations of 4.3 and 4.4 mg/mL were
      synthesized for dihydrofolate reductase and beta-galactosidase, respectively.
      Using the optimized system, the synthesized protein represented 30% (w/w) of the
      total protein, which is comparable to the level of overexpressed protein in
      Escherichia coli cells. This optimized reconstituted in vitro protein synthesis
      system may potentially be useful for various applications, including in vitro
      directed evolution of proteins, artificial cell assembly, and protein structural
      studies. 

PMID- 24880500
TI  - Clinical signs and bacterial communities of deciduous necrotic root canals
      detected by PCR-DGGE analysis: research association.
AB  - OBJECTIVE: This study sought to investigate the possible association between
      clinical and radiographic data of the patients with the bacterial community
      profiles involved in cases of necrosis in primary root canals. METHODS: Microbial
      community profiles for 25 samples from necrotic deciduous root canals were
      analyzed using the polymerase chain reaction-denaturing gradient gel
      electrophoresis (PCR-DGGE) fingerprinting approach. These results were related to
      the clinical and radiographic data of these patients. RESULTS: The analysis
      showed a large diversity of microbial communities in necrotic deciduous root
      canals. The statistical results pointed out that posterior and anterior teeth
      were associated with <20 bands and >20 bands in PCR-DGGE method, respectively. A
      relationship was verified between ages >4 years old and posterior teeth and, ages
      <=4 years old and anterior teeth. CONCLUSIONS: The data showed a polymicrobial
      community and pointed out the association of age with necrosis in anterior and
      posterior teeth.

PMID- 24880502
TI  - T cells and their cytokines in persistent stimulation of the immune system.
AB  - Age-dependent dysregulations of innate immunity impair effective priming of
      adaptive immunity. Alteration of helper functions of CD4 T cells during aging
      prevents them from sustaining cytotoxic responses of CD8 T cells against
      pathogens. The main characteristics of aged and/or differentiated T cells
      included telomere erosion, reduction of proliferation, decrease of IL-2 secretion
      and responsiveness, loss of CD28 and acquisition of cytotoxic properties.
      Phenotypic and functional modifications associated with aging affect development,
      differentiation, exhaustion/senescence status, migration, signalisation and
      metabolism of T lymphocytes. Magnitude and breadth of T cells responses are also
      regulated by the nature and extent of APCs activation. In our review, we focus on
      how the T cells age chronologically and within a persistent infection context.
      The T cell classification is not discussed in details here as it has been
      recently well documented [1(*)] however we focus on how cytokines may participate
      in immune senescence. 

PMID- 24880501
TI  - Periodontal disease and metabolic syndrome: a qualitative critical review of
      their association.
AB  - BACKGROUND: Metabolic syndrome (MetS) is a conglomerate of several physical
      conditions/diseases that, as a group, increases the risk of mortality resulting
      from development of T2DM and cardiovascular diseases (CVD). These
      conditions/diseases include glucose intolerance/insulin resistance, hypertension,
      obesity, and dyslipidemia. The results from epidemiological studies suggest that
      there is an association between metabolic syndrome (MetS) and periodontitis, it
      is therefore important to understand the current status of the association and a
      possible contribution of periodontitis to MetS. OBJECTIVE: This review will
      qualitatively analyze published papers on the association of MetS and
      periodontitis/periodontal disease to clarify the current status of the
      association and suggest future directions for studies which may unravel the
      causal relationship between them. RESULTS: Of 309 papers related to MetS and
      periodontitis, 26 are original research papers that investigated the
      relationship/association between periodontal disease and MetS. Criteria used to
      assess periodontitis and MetS as well as overall study designs and patient
      recruitment criteria varied greatly among these studies. CONCLUSION: All these
      studies demonstrated a positive association between periodontal disease and MetS.
      However, due to the heterogeneity of criteria to assess periodontitis and MetS
      and also paucity of longitudinal studies, it is difficult to determine the
      relative contribution of periodontitis to MetS. Age and the number of positive
      components of MetS appear to strengthen the relationship, however, incidence of
      each disease entity increases with ageing. Thus, mechanistic studies are also
      necessary to unravel the inter-relationship between periodontitis and MetS. In
      this regard, a use of animal models will be helpful as they are more uniform in
      regards to genetic background and have minimum confounding factors. Finally,
      development of accurate, quantitative assessment of gingival inflammation are
      necessary in order to determine the influence of periodontal disease on the
      development of MetS and its components.

PMID- 24880503
TI  - Pharmacologic augmentation of extinction learning during exposure therapy for
      PTSD.

PMID- 24880504
TI  - Short-term treatment as long-term prevention: can early intervention produce
      legacy effects?

PMID- 24880505
TI  - Family-focused therapy study raises new questions.

PMID- 24880506
TI  - Chronic non-episodic irritability in childhood: current and future challenges.

PMID- 24880507
TI  - Anxiety disorders, obsessive-compulsive and related disorders, trauma- and
      stressor-related disorders, and dissociative disorders in DSM-5.

PMID- 24880508
TI  - The suprasensory world of bipolar II disorder.

PMID- 24880509
TI  - Antipsychotic treatment in breast cancer patients.
AB  - Special consideration is required when prescribing antipsychotic drugs for
      patients with an existing diagnosis of breast cancer. The package inserts of all
      approved antipsychotics contain precautions regarding their administration in
      this patient group. These drugs are well known to elevate serum prolactin levels
      to varying degrees. Overexpression of the prolactin receptor is seen in more than
      95% of human breast cancers. Many genes that are activated by the prolactin
      receptor are associated with tumorigenesis and cancer cell proliferation. The
      authors discuss the pathophysiology, clinical implications, and pertinent
      preclinical data and make specific recommendations regarding the use of
      antipsychotics in patients with breast cancer. 

PMID- 24880510
TI  - Long-standing depression and anxiety in a Korean woman.

PMID- 24880511
TI  - Zofiowka Sanatorium.

PMID- 24880512
TI  - Potentiation of the effect of buprenorphine/naloxone with gabapentin or
      quetiapine.

PMID- 24880513
TI  - The second-oldest state psychiatric hospital in the United States.

PMID- 24880514
TI  - Response to Gorelick.

PMID- 24880515
TI  - Limitations of computerized adaptive testing for anxiety.

PMID- 24880522
TI  - Body mass index and retinopathy in Asian populations with diabetes mellitus.
AB  - Body mass index (BMI) is an established risk factor for diabetes. However, the
      association between BMI and diabetic retinopathy (DR) has been inconclusive. We
      aimed to assess the association between BMI and DR in a large population-based
      sample of multi-ethnic Asian adults in Singapore. We examined 2,278 adults aged
      >=40 years with diabetes who participated in three population-based studies
      conducted from 2004 to 2011: the Singapore Malay Eye Study, the Singapore Indian
      Eye Study, and the Singapore Chinese Eye Study. Retinal photographs taken from
      both eyes were graded for any and vision-threatening (VTDR) using the modified
      Airlie House Classification. BMI (kg/m(2)) was categorized into
      normal/underweight (<25), overweight (25-29.9), and obese (>=30). The prevalence
      rates of any and VTDR in the study population were 35.1 % and 9.1 %,
      respectively. The prevalence of any and VTDR decreased with increasing categories
      of BMI (P trend <0.001 and 0.005). In multivariable models adjusted for potential
      confounders, compared to those with normal weight, the odds ratio (95 %
      confidence interval) of any DR was 0.71 (0.57-0.88) for overweight and 0.70 (0.53
      0.92) for obese. Corresponding estimates for VTDR were 0.84 (0.59-1.21) for
      overweight and 0.58 (0.35-0.94) for obese. The inverse association between BMI
      and any DR was consistently present when BMI was analyzed as a continuous
      variable and in analyses stratified by ethnicity and age. In a population-based
      sample of multi-ethnic Asian adults, BMI levels were inversely associated with
      any DR and VTDR.

PMID- 24880524
TI  - [Effects of a neuropsychology program based on mindfulness on Alzheimer's
      disease: randomized double-blind clinical study].
AB  - INTRODUCTION: The purpose of this research was to assess effects of a mindfulness
      based neuropsychological intervention on the clinical course of Alzheimer's
      disease. MATERIAL AND METHOD: A two year randomized and double blind clinical
      trial was conducted on 127 probable Alzheimer's disease patients, according to
      NINCDS-ADRDA scale. Patients were grouped into three experimental groups
      (cognitive stimulation, progressive muscular relaxation, and mindfulness) plus a
      control group. All participants were receiving donepezil. Cognitive skills were
      assessed with CAMCOG and MMSE, functional area with RDRS-2, and NPI was used for
      psychopathology screening. Three treatment sessions per week were carried out for
      two years, and follow up measurements were taken every six months. RESULTS: The
      global cognitive function, functionality and behavioral disorders measurements
      indicated that patients from the experimental group based on mindfulness were
      stable during the two years, while patients from the control group, as well as
      the other experimental groups, showed a mild but significant worsening of their
      mental capacities. CONCLUSION: The mindfulness based neuropsychological program
      showed better cognitive and functional stability, as well as significant
      improvement in the psychopathological condition of mild to moderate Alzheimer'
      patients. These results support the idea that a mindfulness based intervention
      can produce a clinically relevant improvement in the treatment of dementia. More
      research is needed to confirm these data.

PMID- 24880523
TI  - Prediction of the hazard of foetal malformation in pregnant women with epilepsy.
AB  - The data collected in the Australian Register of antiepileptic drugs in pregnancy
      have been studied in the hope of defining simple items of information that could
      be recorded at initial interview of pregnant women with epilepsy, and which might
      allow estimation of the risk of the pregnancy resulting in a malformed foetus.
      Analysis of the data showed that dose of valproate, but not intake of other
      commonly used antiepileptic drugs, in the current pregnancy, and a past history
      of a pregnancy involving a malformed foetus, statistically significantly
      increased the malformation hazard in the current pregnancy, and that continuing
      alcohol intake might decrease it. Plotting the hazard against valproate dose in
      monotherapy, with or without histories of (i) previous pregnancies with foetal
      malformations (FMs), and (ii) continuing alcohol intake, provided quantitative
      information concerning the degree of increased risk. It is hoped that this
      information may help in advising about the risk of foetal malformation (FM) in
      individual pregnancies. 

PMID- 24880525
TI  - Epigallocatechin-3-gallate inhibits proliferation of human aortic smooth muscle
      cells via up-regulating expression of mitofusin 2.
AB  - Previous studies have shown that epigallocatechin-3-gallate (EGCG) inhibits the
      proliferation of vascular smooth muscle cells (VSMCs) via the extracellular
      signal-regulated kinase (ERK1/2) and mitogen activated protein kinases (MAPKs)
      pathway. Mitofusin 2 (Mfn-2) also suppresses VSMC proliferation through Ras-Raf
      ERK/MAPK, suggesting a possible link between EGCG, Mfn-2 and ERK/MAPK. However,
      the effect of EGCG on Mfn-2 remains unknown. In this study, we investigated the
      role of Mfn-2 in the regulation of VSMC proliferation by EGCG, and assessed the
      underlying mechanisms. The effects of EGCG on the proliferation of cultured human
      aortic smooth muscle cells (HASMCs) were observed by 5-ethynl-2-deoxyuridine
      (EdU) incorporation assay. Mfn-2 gene and protein levels, and Ras, p-c-Raf and p
      ERK1/2 protein levels were determined by quantitative real-time polymerase chain
      reaction and western blotting, respectively. Mfn-2 gene silencing was achieved by
      RNA interference. EGCG 50 MUmol/L profoundly inhibited the proliferation of
      HASMCs in culture, up-regulated Mfn-2, and down-regulated the expression of p-c
      Raf and p-ERK1/2. Furthermore, RNA interference-mediated gene knockdown of Mfn-2
      antagonized EGCG-induced anti-proliferation and down-regulation of Ras, p-c-Raf
      and p-ERK1/2. These results suggest that EGCG inhibits the proliferation of
      HASMCs in vitro largely via Mfn-2-mediated suppression of the Ras-Raf-ERK/MAPK
      signaling pathway.

PMID- 24880526
TI  - Life after cancer: how does public stigma increase psychological distress of
      childhood cancer survivors?
AB  - BACKGROUND: Public stigma is a major source of stress for cancer survivors.
      However, factors that buffer or exacerbate the negative effects of public stigma
      on psychological distress have not been elucidated. OBJECTIVE: This study
      examined how perceived public stigma affects psychological distress as mediated
      by cancer disclosure, internalized reactions to stigma, and social support
      availability. DESIGN: Cross-sectional study. SETTINGS: The study was conducted in
      South Korea. PARTICIPANTS: The study sample was 223 adolescent and young adult
      survivors of childhood cancer diagnosed before the age of 19 and currently
      between 15 and 39 years old. METHODS: Psychological distress was assessed using
      the Brief Symptom Inventory-18. Structural equation modeling was used with 1000
      bootstrap samples. RESULTS: The goodness of model fit was acceptable. Public
      stigma perceived by cancer survivors influenced psychological distress via cancer
      disclosure, internalized shame, and social support availability. Higher levels of
      perceived public stigma predicted higher levels of internalized shame and self
      blame and lower levels of social support availability, which subsequently
      increased psychological distress. Higher levels of perceived public stigma
      predicted lower levels of disclosure about cancer history and experiences. Cancer
      disclosure indirectly ameliorated psychological distress by reducing internalized
      shame. CONCLUSIONS: This study offers evidence that cognitive and social factors
      play important roles in mediating the effects of perceived public stigma on
      psychological distress in Korean cancer survivors. A greater understanding of
      factors that influence psychological distress may help psychosocial oncology
      service providers to identify childhood cancer survivors in need of psychosocial
      services and provide them with appropriate resources and interventions.

PMID- 24880527
TI  - Optimizing the transfer of [18F]fluoride from aqueous to organic solvents by
      electrodeposition using carbon electrodes.
AB  - The effect of varying structural modifications of carbon anodes, ranging from
      thin layers of crystalline boron-doped diamond up to highly graphitic bulk
      materials, was systematically examined for the possibility of electrochemical
      fixation and desorption of no-carrier-added [(18)F]fluoride from an aqueous
      solution. Pyrolysed carbon, i.e. "glassy carbon" (Sigradur((r))G), proved as the
      most efficient material for deposition and release. An overall radiochemical
      yield of about 60% was achieved when using this for fixation and DMSO/ionic
      additive as organic solution for the release of [(18)F]fluoride. 

PMID- 24880528
TI  - Cross section measurements of proton and deuteron induced reactions on natural
      europium and yields of SPECT-relevant radioisotopes of gadolinium.
AB  - The existing cross section data of the (nat)Eu(d,x) and (nat)Eu(p,x) reactions
      relevant for the production of (147,149)Gd were expanded up to 70.9 MeV and 44.8
      MeV, respectively. Integral yields of radiogadolinium were calculated, showing
      production rates higher than for the earlier proposed irradiation of highly
      enriched (144)Sm with alpha- or (3)He-particles. The formation of radioisotopic
      impurities like (151)Gd (T(1/2)=124 d) and (153)Gd (T(1/2)=240 d) was below 5%.
      Production of (147,)(149)Gd using enriched europium is also discussed.

PMID- 24880529
TI  - Endoscopic gastric submucosal dissection in low-grade intraepithelial neoplasia.

PMID- 24880530
TI  - [Colonic mass secondary to actinomycosis: a case report and literature review].

PMID- 24880531
TI  - European Cystic Fibrosis Society Standards of Care: a road map to improve CF
      outcome.

PMID- 24880532
TI  - ESCF care guidelines beyond Europe.

PMID- 24880533
TI  - Species- and tissue-specific bioaccumulation of arsenicals in various aquatic
      organisms from a highly industrialized area in the Pohang City, Korea.
AB  - Contamination of water and sediment with arsenic (As) in a highly industrialized
      area of Pohang City, Korea was investigated, with emphasis on in situ
      bioaccumulation of arsenicals by various aquatic organisms. Species- and tissue
      specific concentrations of arsenicals were determined by use of HPLC-ICP/MS and
      MU-X-ray absorption near-edge structure (MU-XANES). Concentrations of arsenic in
      aquatic organisms were strongly associated with corresponding water
      concentrations, which indicates point sources associated with land use and
      activities. Arsenobetaine was the most dominant form of arsenic found in fishes,
      bivalves, crabs, and shrimps, while As(III) was predominant in freshwater snails.
      The MU-XANES analysis provided additional information about the unidentified
      arsenicals such as As-thiol. Arsenicals were mainly localized in intestine of
      mullet and marsh clam. Distribution and bioaccumulation of arsenic were strongly
      correlated with salinity, which indicates that natural processes controlling
      biogeochemistry of arsenic would be important in estuarine lotic system. 

PMID- 24880534
TI  - Transport of surfactant-facilitated multiwalled carbon nanotube suspensions in
      columns packed with sized soil particles.
AB  - Transport of carbon nanotubes (CNTs) in soil/sediment matrixes can regulate their
      potential eco-effects and has been however rarely studied. Herein, column
      experiments were conducted to investigate mobility of CNT suspensions stabilized
      by dodecylbenzenesulfonic acid sodium salt (SDBS), octyl-phenol-ethoxylate (TX
      100) and cetylpyridinium chloride (CPC) in four soil samples with certain
      particle sizes. Humic acid was extracted from a soil sample and was coated on
      quartz sands to explore the effect of soil organic matter (SOM) on the mobility.
      Results showed that the positively-charged CPC-CNT was entirely retained in the
      columns while the negatively-charged SDBS-CNT and TX-100-CNT more or less broke
      through the columns. Pearson correlation analyses revealed that soil texture
      rather than SOM controlled the mobility. Electrostatic attraction to and/or
      precipitation on the grain surfaces together with the straining effect could
      explain the CNT retention. These novel results will help to understand the eco
      effects of CNTs. 

PMID- 24880535
TI  - Atmospheric transport and accumulation of organochlorine compounds on the
      southern slopes of the Himalayas, Nepal.
AB  - Studies have been devoted to the transport and accumulation of persistent organic
      pollutants (POPs) in mountain environments. The Himalayas have the widest
      altitude gradient of any mountain range, but few studies examining the
      environmental behavior of POPs have been performed in the Himalayas. In this
      study, air, soil, and leaf samples were collected along a transect on the
      southern slope of the Himalayas, Nepal (altitude: 135-5100 m). Local emission
      occurred in the lowlands, and POPs were transported by uplift along the slope.
      During the atmospheric transport, the HCB proportion increased from the lowlands
      (20%) to high elevation (>50%), whereas the proportions of DDTs decreased. The
      largest residue of soil POPs appeared at an altitude of approximately 2500 m, and
      may be related to absorption by vegetation and precipitation. The net deposition
      tendencies at the air-soil surface indicated that the Himalayas may be a 'sink'
      for DDTs and PCBs. 

PMID- 24880536
TI  - High levels of global DNA methylation are an independent adverse prognostic
      factor in a series of 90 patients with de novo myelodysplastic syndrome.
AB  - The prognostic impact of global DNA methylation and hydroxymethylation was
      assessed in 90 patients with de novo myelodysplastic syndrome (MDS). DNA was
      isolated from bone marrow samples obtained at diagnosis and global methylation
      and hydroxymethylation were determined by ELISA. Patients with a percentage of
      methylated DNA above 2.73% had a shorter overall survival than those with lower
      levels (P=0.018) and presented a negative trend in terms of leukemia-free
      survival (P=0.084), that was statistically significant after censoring 9 patients
      that received disease-modifying treatments both in univariate and multivariate
      analyses. Similarly, the low-risk MDS patients defined by the IPSS, WPSS and IPSS
      R with 5-mC percentage in total DNA above 2.73% had a shorter overall survival
      (P=0.032; P=0.023; P=0.031). No cut-off value for the 5-hydroxymethylcytosine
      percentage with statistical significance for overall or leukemia-free survival
      was obtained. This study suggests that global DNA methylation predicts overall
      survival in myelodysplastic syndromes. 

PMID- 24880537
TI  - Primary natural killer/T-cell lymphoma presenting as leptomeningeal disease.
AB  - INTRODUCTION: Primary central nervous system natural killer/T-cell lymphoma
      (primary-CNS-NK/TCL) is a rare non-Hodgkin's lymphoma. To our knowledge, only
      five patients have been described previously, all of whom were male, with brain
      parenchymal involvement and previous Epstein-Barr virus infection, it has never
      been reported to present as leptomeningeal disease as our case. Our objective is
      to report a rare case of primary-CNS-NK/TCL presenting as leptomeningeal disease
      and to share our diagnostic/therapeutic approach to this rare disease. METHODS:
      We report a rare case of primary-CNS-NK/TCL presenting as leptomeningeal disease.
      The patient was diagnosed and treated at The University of Texas MD Anderson
      Cancer Center. RESULTS: The patient presented with multiple cranial neuropathies
      and gait ataxia. Brain and spinal cord magnetic resonance imaging demonstrated
      leptomeningeal enhancement of the cerebellar folia/vermis, spinal cord dura, and
      both temporal lobes as well as adjacent brain parenchymal disease. Cerebrospinal
      fluid (CSF) revealed atypical lymphoma cells of NK/T-cell lineage by flow
      cytometric immunophenotyping. Molecular analysis using real-time quantitative
      polymerase chain reaction did not detect Epstein-Barr virus DNA in the lymphoma
      cells. Bone marrow biopsy revealed no morphologic, flow cytometric, or
      immunohistochemical evidence of B-, T- or NK-cell lymphoma. Slit-lamp examination
      demonstrated no evidence of intraocular lymphoma. Whole-body PET scan showed no
      evidence of malignancy other than CNS disease. The patient was given systemic
      chemotherapy with high-dose methotrexate, vincristine, and procarbazine, along
      with intrathecal therapy with free cytarabine. The patient showed
      clinicoradiographic improvement and CSF cytology became negative. CONCLUSION:
      This case highlights an atypical presentation of primary-CNS-NK/TCL with a
      potentially successful treatment regimen.

PMID- 24880538
TI  - The safety of exercise training in multiple sclerosis: a systematic review.
AB  - There are many reviews documenting the benefits of exercise training among
      persons with multiple sclerosis (MS). To date, we are unaware of a review that
      summarizes the risks of relapse and other adverse events (AEs) associated with
      exercise training, yet this is critical for informing decisions and
      recommendations regarding the safety of this behavior. We conducted a systematic
      review of relapse and other AEs reported in randomized controlled trials (RCTs)
      of exercise training in MS. We searched electronic databases for RCTs of exercise
      training in MS. We calculated the rate of relapse and AEs, and the relative risk
      of relapse and AEs for exercise training versus control. Twenty-six studies were
      reviewed that included 1295 participants. We determined that the rate of relapse
      was 6.3% and 4.6% for control and exercise, respectively. The rate of AEs was
      1.2% and 2.0% for control and exercise, respectively. The relative risk of
      relapse for exercise training was 0.73, whereas the relative risk of AE for
      exercise training was 1.67. Exercise training was not associated with an
      increased risk of relapse, and risk of AEs was not higher than in healthy
      populations. This evidence should alleviate uncertainty regarding the safety of
      exercise training in MS. 

PMID- 24880539
TI  - Underestimation of cognitive impairments by the Montreal Cognitive Assessment
      (MoCA) in an acute stroke unit population.
AB  - BACKGROUND AND PURPOSE: The Montreal Cognitive Assessment (MoCA) is an
      increasingly popular clinical screening tool for detecting cognitive impairment
      in stroke, but few studies have directly compared performance on the MoCA with
      neuropsychological assessment. Our retrospective study examined the extent to
      which intact performance on the MoCA reflects intact cognition as determined by
      neuropsychological assessment. METHODS: In this retrospective study, cognitive
      profiles for 136 acute stroke patients admitted to the Acute Stroke Unit who had
      available MoCA and neuropsychological assessment data were examined. RESULTS: 22%
      of our patients were deemed cognitively intact on the MoCA. Of these, 78% were
      found to be impaired (<= 5%ile) on neuropsychological assessment in one or more
      cognitive domains. The most common impairments were in general intelligence,
      information processing speed and visual memory; three areas not assessed by the
      MoCA. In addition, a high proportion (up to 59%) of patients who scored the
      maximum points in one of the MoCA-specified domains were impaired on comparable
      neuropsychological assessment. CONCLUSIONS: Our findings suggest that although
      the MoCA may be a useful screening tool post-stroke in detecting gross
      impairments, neuropsychological assessment is still necessary for a comprehensive
      and reliable detection of domain-specific cognitive deficits, which can more
      reliably inform us for realistic goal setting and vocational advice vital for
      effective rehabilitation.

PMID- 24880540
TI  - A novel LITAF/SIMPLE mutation within a family with a demyelinating form of
      Charcot-Marie-Tooth disease.
AB  - Charcot-Marie-Tooth disease type 1 (CMT1) is a common disorder of the peripheral
      nervous system. The underlying genetic cause is highly heterogeneous, and
      mutations in SIMPLE (small integral membrane protein of lysosome/late endosome)
      represent a rare cause of CMT type 1, named CMT1C. Herein, we report the
      clinical, electrophysiological, and neuropathological findings of an Italian CMT1
      family with a novel SIMPLE missense mutation. The family exhibited
      electrophysiological signs of demyelination, predominantly affecting the lower
      limbs, with conduction blocks, and a wide variability of age of onset among the
      members. Molecular analysis identified the novel heterozygous missense mutation
      p.Pro135Arg in SIMPLE which co-segregated with the disease within the pedigree.
      In conclusion, our findings confirm that the genetic analysis of LITAF/SIMPLE
      should be considered for the diagnostic flow-chart of CMT1 patient, especially
      when nerve conduction studies show the presence of conduction blocks. 

PMID- 24880541
TI  - Glycine receptor antibodies in a boy with focal epilepsy and episodic behavioral
      disorder.
AB  - A wide range of clinical presentations including neuromuscular disorders and
      autoimmune encephalopathies is being recognized to be associated with various
      autoantibodies. Glycine receptor (GlyR) antibodies have so far been found mainly
      in adult patients with phenotypes comprising progressive encephalomyelitis with
      rigidity and myoclonus or stiff-person syndrome. We report a four-year-old boy
      who presented with a two-year-history of drug-resistant focal epilepsy with
      unusual seizure semiology, temper tantrums, headache, clumsiness, and
      intermittently impaired speech. While MRI and CSF were normal, screening for
      autoimmune antibodies revealed GlyR antibodies in serum. Immunomodulatory
      treatment with steroids resulted in rapid and complete resolution of symptoms.
      Our observation widens the spectrum of clinical presentations associated with
      GlyR antibodies and emphasizes the potential relevance of neuronal autoantibodies
      in epilepsies of unknown cause in children as well as in adults. 

PMID- 24880543
TI  - Challenges associated with projecting urbanization-induced heat-related
      mortality.
AB  - Maricopa County, Arizona, anchor to the fastest growing megapolitan area in the
      United States, is located in a hot desert climate where extreme temperatures are
      associated with elevated risk of mortality. Continued urbanization in the region
      will impact atmospheric temperatures and, as a result, potentially affect human
      health. We aimed to quantify the number of excess deaths attributable to heat in
      Maricopa County based on three future urbanization and adaptation scenarios and
      multiple exposure variables. Two scenarios (low and high growth projections)
      represent the maximum possible uncertainty range associated with urbanization in
      central Arizona, and a third represents the adaptation of high-albedo cool roof
      technology. Using a Poisson regression model, we related temperature to mortality
      using data spanning 1983-2007. Regional climate model simulations based on 2050
      projected urbanization scenarios for Maricopa County generated distributions of
      temperature change, and from these predicted changes future excess heat-related
      mortality was estimated. Subject to urbanization scenario and exposure variable
      utilized, projections of heat-related mortality ranged from a decrease of 46
      deaths per year (-95%) to an increase of 339 deaths per year (+359%). Projections
      based on minimum temperature showed the greatest increase for all expansion and
      adaptation scenarios and were substantially higher than those for daily mean
      temperature. Projections based on maximum temperature were largely associated
      with declining mortality. Low-growth and adaptation scenarios led to the smallest
      increase in predicted heat-related mortality based on mean temperature
      projections. Use of only one exposure variable to project future heat-related
      deaths may therefore be misrepresentative in terms of direction of change and
      magnitude of effects. Because urbanization-induced impacts can vary across the
      diurnal cycle, projections of heat-related health outcomes that do not consider
      place-based, time-varying urban heat island effects are neglecting essential
      elements for policy relevant decision-making. 

PMID- 24880542
TI  - Chemical characterization and source apportionment of indoor and outdoor fine
      particulate matter (PM(2.5)) in retirement communities of the Los Angeles Basin.
AB  - Concurrent indoor and outdoor measurements of fine particulate matter (PM2.5)
      were conducted at three retirement homes in the Los Angeles Basin during two
      separate phases (cold and warm) between 2005 and 2006. Indoor-to-outdoor
      relationships of PM2.5 chemical constituents were determined and sources of
      indoor and outdoor PM2.5 were evaluated using a molecular marker-based chemical
      mass balance (MM-CMB) model. Indoor levels of elemental carbon (EC) along with
      metals and trace elements were found to be significantly affected by outdoor
      sources. EC, in particular, displayed very high indoor-to-outdoor (I/O) mass
      ratios accompanied by strong I/O correlations, illustrating the significant
      impact of outdoor sources on indoor levels of EC. Similarly, indoor levels of
      polycyclic aromatic hydrocarbons (PAHs), hopanes, and steranes were strongly
      correlated with their outdoor components and displayed I/O ratios close to unity.
      On the other hand, concentrations of n-alkanes and organic acids inside the
      retirement communities were dominated by indoor sources (e.g. food cooking and
      consumer products), as indicated by their I/O ratios, which exceeded unity.
      Source apportionment results revealed that vehicular emissions were the major
      contributor to both indoor and outdoor PM2.5, accounting for 39 and 46% of total
      mass, respectively. Moreover, the contribution of vehicular sources to indoor
      levels was generally comparable to its corresponding outdoor estimate. Other
      water-insoluble organic matter (other WIOM), which accounts for emissions from
      uncharacterized primary biogenic sources, displayed a wider range of
      contributions, varying from 2 to 73% of PM2.5, across all sites and phases of the
      study. Lastly, higher indoor than outdoor contribution of other water-soluble
      organic matter (other WSOM) was evident at some of the sites, suggesting the
      production of secondary aerosols as well as direct emissions from primary sources
      (including cleaning or other consumer products) at the indoor environments. 

PMID- 24880544
TI  - Chronic exposure to odorous chemicals in residential areas and effects on human
      psychosocial health: dose-response relationships.
AB  - Perceived air pollution, including environmental odor pollution, is known to be
      an environmental stressor that affects individuals' psychosocial health and well
      being. However, very few studies have been able to quantify exposure-response
      associations based on individual-specific residential exposures to a proxy gas
      and to examine the mechanisms underlying these associations. In this study,
      individual-specific exposures in non-urban residential environments during 2005
      2010 on a gas released from animal biodegradable wastes (ammonia, NH3) were
      calculated by the Danish Eulerian long-range transport model and the local-scale
      transport deposition model. We used binomial and multinomial logistic regression
      and mediation analyses to examine the associations between average exposures and
      questionnaire-based data on psychosocial responses, after controlling for person
      specific covariates. About 45% of the respondents were annoyed by residential
      odor pollution. Exposures were associated with annoyance (adjusted odds ratio
      [ORadj]=3.54, 95% confidence interval [CI]=2.33-5.39), health risk perception
      (ORadj=4.94; 95% CI=1.95-12.5) and behavioral interference (ORadj=3.28; 95%
      CI=1.77-6.11), for each unit increase in loge(NH3 exposure). Annoyance was a
      strong mediator in exposure-behavior interference and exposure-health risk
      perception relationships (81% and 44% mediation, respectively). Health risk
      perception did not play a mediating role in exposure-annoyance or exposure
      behavioral interference relationships. This is the first study to provide a
      quantitative estimation of the dose-response associations between ambient NH3
      exposures and psychosocial effects caused by odor pollution in non-urban
      residential outdoor environments. It further shows that these effects are both
      direct and mediated by other psychosocial responses. The results support the use
      of NH3 as a proxy gas of air pollution from animal biodegradable wastes in
      epidemiologic studies. 

PMID- 24880545
TI  - Polychlorinated naphthalenes in sewage sludge from wastewater treatment plants in
      China.
AB  - Polychlorinated naphthalenes (PCNs) were nominated as persistent organic
      pollutants candidate in the Stockholm Convention in 2011. In this study, the
      profiles, concentrations and spatial distributions of PCNs were analyzed in 30
      sewage sludge samples from wastewater treatment plants (WWTPs) in China.
      Concentrations of Sigma75PCNs in sludge samples were in the range of 1.05-10.9
      ng/g dry weight (dw) with a mean value of 3.98 ng/g dw. The predominant
      homologues in the sludge were mono- to tetra-CNs, accounting for approximately
      85% of total PCNs. The total toxic equivalent quantities (TEQs) of dioxin-like
      PCN congeners ranged from 0.04 to 2.28 pg/g dw with a mean value of 0.36 pg/g dw,
      which were lower than the maximum permissible TEQ concentrations in sludge for
      land application in China. Levels of PCNs and TEQs in sludge were relatively
      higher in samples from highly industrialized and developed cities in eastern
      China, implying a possible link between PCN contamination and the local economic
      development, but more studies are warranted to corroborate this. Industrial
      sources might be important contributors of PCNs to sewage sludge in China.

PMID- 24880546
TI  - Influence of monsoons on atmospheric CO2 spatial variability and ground-based
      monitoring over India.
AB  - This study examines the role of Asian monsoons on transport and spatial
      variability of atmospheric CO2 over the Indian subcontinent, using transport
      modeling tools and available surface observations from two atmospheric CO2
      monitoring sites Sinhagad (SNG) and Cape Rama (CRI) in the western part of
      peninsular India. The regional source contributions to these sites arise from the
      horizontal flow in conduits within the planetary boundary layer. Greater CO2
      variability, greater than 15 ppm, is observed during winter, while it is reduced
      nearly by half during summer. The SNG air sampling site is more susceptible to
      narrow regional terrestrial fluxes transported from the Indo-Gangetic Plains in
      January, and to wider upwind marine source regions from the Arabian Sea in July.
      The Western Ghats mountains appear to play a role in the seasonal variability at
      SNG by trapping polluted air masses associated with weak monsoonal winds. A
      Lagrangian back-trajectory analysis further suggests that the horizontal extent
      of regional sensitivity increases from north to south over the Indian
      subcontinent in January (Boreal winter).

PMID- 24880547
TI  - Developing resilient green roofs in a dry climate.
AB  - Living roofs are an emerging green infrastructure technology that can potentially
      be used to ameliorate both climate change and urban heat island effects. There is
      not much information regarding the design of green roofs for dry climates and so
      the aim of this study was to develop low maintenance and unfertilized green roofs
      for a dry climate. This paper describes the effects of four important elements of
      green roofs namely slope, depth, growing media and plant species and their
      possible interactions in terms of plant growth responses in a dry climate.
      Sixteen medium-scale green roofs were set up and monitored during a one year
      period. This experiment consisted of twelve vegetated platforms and four non
      vegetated platforms as controls. The design for the experiment was a split-split
      plot design in which the factors Slope (1 degrees  and 25 degrees ) and Depth
      (100mm, 300 mm) were randomized to the platforms (main plots). Root depth and
      volume, average height of plants, final dry biomass and ground cover, relative
      growth rate, final dry shoot-root ratio, water use efficiency and leaf succulence
      were studied during a twelve month period. The results showed little growth of
      the plants in media type A, whilst the growth was significant in both media types
      B and C. On average, a 90% survival rate of plants was observed. Also the growth
      indices indicated that some plants can grow efficiently in the harsh environment
      created by green roofs in a dry climate. The root growth pattern showed that
      retained water in the drainage layer is an alternative source of water for
      plants. It was also shown that stormwater can be used as a source of irrigation
      water for green roofs during six months of the year at the study site. In
      summary, mild sloping intensive systems containing media type C and planted with
      either Chrysocephalum apiculatum or Disphyma crassifolium showed the best
      performance.

PMID- 24880548
TI  - Arsenic mobilization in aquifers of the southwest Songnen basin, P.R. China:
      evidences from chemical and isotopic characteristics.
AB  - High As groundwater has widely been found in the inland basins of China. Little
      is known about distribution and mobilization mechanisms of high As groundwater in
      the Songnen basin, where groundwater is the major source for drinking and
      irrigation. Eighty-seven groundwater samples, three surface water samples and
      sixty-three sediment samples were taken from the southwest of the Songnen basin,
      in order to investigate spatial distribution and constrains of groundwater As.
      Results showed that high As groundwater was generally of Na-Mg/Ca-HCO3 type,
      which had relatively low Eh values and neutral-weakly alkaline pH. High As
      groundwater was characterized by low concentrations of NO3(-) and SO4(2-), and
      high concentrations of Fe, Mn, and H2S. Around 65.5% of sampled shallow
      groundwater and 96% of sampled deep groundwater had As concentrations greater
      than 10 MUg/L. Sediments had higher total As contents and higher Fe/Mn oxide
      bound As contents in high As groundwater area than in the low As groundwater
      area. Distribution of groundwater As was dependent upon hydrogeologic settings,
      redox potential, microbial degradation of organic carbon, and precipitation of
      pyrite, siderite, and calcite. Along the groundwater flow path, As concentration
      showed an increasing trend. High As groundwater was mainly distributed in the low
      lying areas. Reducing conditions were the major causes for As mobilization in the
      aquifers, which led to more As released from the sediments with higher contents
      of Fe/Mn oxide-bound As in higher As groundwater area. Results of (13)CDOC and
      (13)CDIC showed that dissimilatory Fe(III) reduction coupled with microbial
      degradation of dissolved organic carbon would be related to As mobilization in
      the aquifers. Although both Fe and As were released during these redox processes,
      pyrite, siderite and calcite precipitation would be the sink of dissolved As,
      which resulted in weak correlation between dissolved Fe and As.

PMID- 24880550
TI  - Toxicity of PHOS-CHEK LC-95A and 259F fire retardants to ocean- and stream-type
      Chinook salmon and their potential to recover before seawater entry.
AB  - Long-term fire retardants are used to prevent the spread of wildland fire, but
      have inadvertently entered aquatic habitats and resulted in fish kills. We
      examined the toxicity of two fire retardant products; PHOS-CHEK 259F and LC-95A,
      on Chinook salmon with two different life histories, ocean-type and stream-type,
      at different stages of their development. Ocean-type Chinook outmigrate to the
      ocean as subyearlings; while, stream-type salmon overwinter in freshwater and
      outmigrate as yearlings. Ocean-type and stream-type salmon were exposed to the
      fire retardants prior to their parr to smolt transition (presmolts) as
      subyearlings (stream-type and ocean-type) and yearlings (stream-type only), as
      well as during their transition (smolts). The salmon were exposed to eight
      concentrations of each retardant and a control for 96h to determine acute
      toxicity. Lethal concentration curves were modeled by logistic regression for
      each life history and life stage exposed to the two fire retardants. Among all
      life histories and life stages tested, PHOS-CHEK 259F was most toxic to stream
      type salmon at smolt stage and PHOS-CHEK LC-95A was most toxic to ocean-type
      salmon at smolt stage. To determine the delayed effects of product exposures on
      fish health as well as for the potential of recovery, 24-hour seawater challenges
      were performed immediately after fire retardant exposure, as well as after a
      recovery period. Previous PHOS-CHEK exposure reduced survival during seawater
      challenge among salmon from both life histories undergoing the parr-smolt
      transition and was more pronounced after PHOS-CHEK LC-95A exposure. However, this
      delayed effect was not observed 34 or more days after either PHOS-CHEK exposure.
      We conclude that accidental PHOS-CHEK LC-95A or 259F drops during salmon
      outmigration would have adverse impacts that extend beyond the acute mortality
      that occurs within the immediate drop and dilution areas. 

PMID- 24880551
TI  - C and N accumulations in soil aggregates determine nitrous oxide emissions from
      cover crop treated rice paddy soils during fallow season.
AB  - Combination of leguminous and non-leguminous plant residues are preferably
      applied in rice paddy soils to increase the rate of organic matter mineralization
      and to improve plant growth. However, organic matter addition facilitates methane
      (CH4) emission from rice paddy soil. Mineralization of organic nitrogen (N)
      increases NO3-N concentrations in soil, which are precursors for the formation of
      nitrous oxide (N2O). However, N2O is a minor greenhouse gas emitted from
      submerged rice field and hence is not often considered during calculation of
      total global warming potential (GWP) during rice cultivation. The hypothesis of
      this study was that fluxes of N2O emissions might be changed after removal of
      flooded water from rice field and the effect of cover crops on N2O emissions in
      the fallow season might be interesting. However, the effects of N-rich plant
      residues on N2O emission rates in the fallow season and its effect on annual GWP
      were not studied before. In this experiment, combination of barley (non
      leguminous) and hairy vetch (leguminous) biomasses were applied at 9 Mg ha(-1)
      and 27 Mg ha(-1) rates in rice paddy soil. Cover crop application significantly
      increased CH4 emission flux while decreased N2O emissions during rice
      cultivation. The lowest N2O emission was observed in 27 Mg ha(-1) cover crop
      treated plots. Cover crop applications increased N contents in soil aggregates
      especially in smaller aggregates (<250 MUm), and that proportionately increased
      the N2O emission potentials of these soil aggregates. Fluxes of N2O emissions in
      the fallow season were influenced by the N2O emission potentials of soil
      aggregates and followed opposite trends as those observed during rice
      cultivation. Therefore, it could be concluded that the doses of cover crop
      applications for rice cultivation should not be optimized considering only CH4,
      but N2O should also be considered especially for fallow season to calculate total
      GWP.

PMID- 24880549
TI  - Association between serum organochlorines and global methylation level of
      leukocyte DNA among Japanese women: a cross-sectional study.
AB  - While the global methylation level of leukocyte DNA may be a suitable biomarker
      for cancer risk, the level may be influenced by multiple factors, both
      environmental and host-related, one of which is exposure to environmental
      pollutants. To date, three epidemiologic studies have examined associations
      between serum organochlorine levels and global DNA methylation level, but their
      findings are not fully consistent, and the associations thus require confirmation
      in other well-characterized populations. We tested the association between
      organochlorine exposure and the global DNA methylation level of leukocytes in
      Japanese women. We conducted a cross-sectional study using the control group of a
      breast cancer case-control study in Japan. Subjects were 403 Japanese women who
      provided blood samples. Serum polychlorinated biphenyls (PCBs) and nine pesticide
      related organochlorines were measured by gas chromatography isotope-dilution high
      resolution mass spectrometry. Further, global methylation level of peripheral
      leukocyte DNA among 399 women was measured by luminometric methylation assay.
      Linear trends in the association between methylation and quartile levels of
      organochlorines were evaluated by regression coefficients in a multivariable
      linear regression model. We found significant inverse associations between the
      global methylation level in leukocyte DNA and many of the organochlorine levels
      measured. Global methylation level was significantly decreased by 0.33-0.83% per
      quartile category for serum o,p'-dichlorodiphenyltrichloroethane (o,p'-DDT), p,p'
      DDT, p,p'-dichlorodiphenyldichloroethylene, trans-nonachlor, oxychlordane,
      hexachlorobenzene, beta-hexachlorocyclohexane, PCB17, PCB52/69, PCB74, PCB114,
      and PCB183. Serum organochlorine levels were inversely associated with the global
      methylation level of leukocyte DNA in a relatively large sample of Japanese
      women. 

PMID- 24880552
TI  - Molecular cloning and functional characterization of the anthocyanidin reductase
      gene from Vitis bellula.
AB  - Anthocyanidin reductase (ANR) is an NADPH-/NADH-dependent enzyme that transfers
      two hydrides to anthocyanidins to produce three types of isomeric flavan-3-ols.
      This reductase forms the ANR pathway toward the biosynthesis of proanthocyanidins
      (PAs, which are also called condensed tannins). Here, we report cloning and
      functional characterization of an ANR (called VbANR) homolog from the leaves of
      Vitis bellula, a newly developed grape crop in southern China. The open reading
      frame (ORF) of VbANR is 1,017 bp in length and encodes 339 amino acids. A
      phylogenetic analysis and an alignment using 17 sequences revealed that VbANR is
      approximately 99.9 % identical to the ANR homolog from Vitis vinifera. The VbANR
      ORF is fused to the Trx gene containing a His-tag in the pET32a(+) vector to
      obtain a pET32a(+)-VbANR construct for expressing the recombinant VbANR. In vitro
      enzyme assays show that VbANR converts cyanidin, delphinidin, and pelargonidin to
      their corresponding flavan-3-ols. Enzymatic products include 2S,3R-trans- and
      2R,3R-cis-flavan-3-ols isomers, such as (-)-catechin and (-)-epicatechin. In
      addition, the third compound that is observed from the enzymatic products is most
      likely a 2S,3S-cis-flavan-3-ol. To analyze the kinetics and optimize pH and
      temperature values, a UV spectrometry method was developed to quantify the
      concentrations of total enzymatic products. The optimum pH and temperature values
      are 4.0 and 40  degrees C, respectively. The K m , K cat, V max, and K cat/K m
      values for pelargonidin and delphinidin were similar. In comparison, VbANR
      exhibits a slightly lower affinity to cyanidin. VbANR uses both NADPH and NADH
      but prefers to employ NADPH. GFP fusion and confocal microscopy analyses revealed
      the cytosolic localization of VbANR. The overexpression of VbANR in ban mutants
      reconstructed the biosynthetic pathway of PAs in the seed coat. These data
      demonstrate that VbANR forms the ANR pathway, leading to the formation of three
      types of isomeric flavan-3-ols and PAs in the leaves of V. bellula.

PMID- 24880553
TI  - Opening the Ralstonia solanacearum type III effector tool box: insights into host
      cell subversion mechanisms.
AB  - Effectors delivered to host cells by the Type III secretion system are essential
      to Ralstonia solanacearum pathogenicity, as in several other plant pathogenic
      bacteria. The establishment of exhaustive effector repertoires in multiple R.
      solanacearum strains drew a first picture of the evolutionary dynamics of the
      pathogen effector suites. Effector repertoires are diversified, with a core of 20
      30 effectors present in most of the strains and the obtention of mutants lacking
      one or more effector genes revealed the functional overlap among this effector
      network. Recent functional studies have provided insights into the ability of
      single effectors to manipulate the host proteasome, elicit cell death, trigger
      the expression of plant genes, and/or display biochemical activities on plant
      protein targets. 

PMID- 24880554
TI  - Tachydysrhythmia treatment and adverse events in patients with wolff-Parkinson
      white syndrome.
AB  - BACKGROUND: Current guidelines recommend avoiding atrioventricular-nodal blocking
      agents (AVNB) when treating tachydysrhythmias in Wolff-Parkinson-White syndrome
      (WPW) patients. STUDY OBJECTIVES: We investigated medications selected and
      resulting outcomes for patients with tachydysrhythmias and WPW. METHODS: In this
      single-center retrospective cohort study, we searched a hospital-wide database
      for the following inclusion criteria: WPW, tachycardia, and intravenous
      antidysrhythmics. The composite outcome of adverse events was acceleration of
      tachycardia, new hypotension, new malignant dysrhythmia, and cardioversion. The
      difference in binomial proportions of patients meeting the composite outcome
      after AVNB or non-AVNB (NAVNB) treatment was calculated after dividing the groups
      by QRS duration. A random-effects mixed linear analysis was performed to analyze
      the vital sign response. RESULTS: The initial database search yielded 1158
      patient visits, with 60 meeting inclusion criteria. Patients' median age was 52.5
      years; 53% were male, 43% presented in wide complex tachycardia (WCT), with 75%
      in atrial fibrillation (AF) or flutter. AVNBs were administered in 42 (70%)
      patient visits. For those patients with WCT in AF, the difference in proportions
      of patients meeting the composite outcome after AVNBs vs. NAVNBs treatment was an
      increase of 3% (95% confidence interval [CI] -39%-49%), and for those with narrow
      complex AF it was a decrease of 13% (95% CI -37%-81%). No instances of malignant
      dysrhythmia occurred. Mixed linear analysis showed no statistically significant
      effects on heart rate, though suggested a trend toward increasing heart rate
      after AVNB in wide complex AF. CONCLUSION: In this sample of WPW-associated
      tachydysrhythmia patients, many were treated with AVNBs. The composite outcome
      was similarly met after use of either AVNB or NAVNB, and no malignant
      dysrhythmias were observed.

PMID- 24880557
TI  - A thought for World Environment Day.

PMID- 24880555
TI  - [Acquired long QT syndrome and cardiac arrest after general anesthesia. Case
      report and review of literature].
AB  - A 30-year-old woman, with no medical history, is operated on for breast implants.
      In recovery room, an episode of torsade de pointes occurs, progressing to
      ventricular fibrillation. The ECG after cardiopulmonary resuscitation and
      conversion to a normal sinus rhythm shows a corrected QT interval prolongation,
      whereas it is normalized after 48hours. We hypothesize that a ventricular
      fibrillation occurred after a torsade de pointes, due to drug-induced long QT
      syndrome during general anesthesia, with probably drug interaction. 

PMID- 24880559
TI  - Bariatric surgery.

PMID- 24880558
TI  - Bariatric surgery.

PMID- 24880560
TI  - Subconjunctival bevacizumab for iris neovascularisation.

PMID- 24880561
TI  - Bariatric surgery.

PMID- 24880562
TI  - Subconjunctival bevacizumab for iris neovascularisation - Authors' reply.

PMID- 24880563
TI  - Should a pilot on insulin really fly?

PMID- 24880564
TI  - Free sugars: the less the better.

PMID- 24880565
TI  - Endocrine aspects of bone metastases.
AB  - Skeletal lesions are a frequent complication of breast and prostate cancer and a
      hallmark of multiple myeloma. Endocrine and paracrine factors modulate various
      aspects of bone metastases, including tumour proliferation, skeletal
      susceptibility to tumour homing, the microenvironment needed to support tumour
      persistence, and the initiation of a vicious cycle between tumour and bone
      resident cells that further promotes tumour growth. Endocrine changes, such as
      oestrogen or vitamin D deficiency, contribute to a fertile bone microenvironment
      that might promote bone metastases. Bone health could be impaired further by
      existing cancer treatments, especially sex hormone deprivation. In this Review,
      we discuss the effect of hormones and associated local factors on cross-talk
      between bone metabolism and tumour biology. We review the biology of osteolytic
      and osteosclerotic lesions, with a focus on endocrine aspects, and outline
      potential therapeutic targets. We also summarise endocrine aspects of the
      pathogenesis and clinical presentation of bone metastases and provide an update
      on existing and future treatments. 

PMID- 24880567
TI  - Effect of thickness of bonded composite resin on compressive strength.
AB  - OBJECTIVE: The aim of this study was to investigate the compressive strength of
      composites with different physical properties bonded as a restoration to dentin
      in layers of varying thicknesses. METHODS: Four types of direct composite
      materials: a midway-filled (Tetric EvoCeram); a compact-filled (Clearfil AP-X); a
      nano-filled (Filtek Supreme); and a micro-filled material (Heliomolar) were
      bonded in 0.5-3.0mm thick layers onto bovine dentin. Each material group
      contained 25 samples, which were loaded until fracture. RESULTS: The nano-filled
      and the compact filled material showed a significant association between layer
      thickness and compressive strength. The midway-filled composite was the most
      consistent material showing similar failure load over the complete thickness
      range. CONCLUSION: A clear influence of layer thickness on compressive strength
      was found in some composite resin materials. When restorations are placed that
      are heavily loaded, such as in patients with severe wear due to bruxism it may be
      advisable to choose a material that is adequately strong in all thicknesses.

PMID- 24880566
TI  - Resistance to impact of cross-linked denture base biopolymer materials: effect of
      relining, glass flakes reinforcement and cyclic loading.
AB  - AIMS: The effect of reinforcement and cyclic loading on the resistance to impact
      (RI) of denture base biopolymer materials was evaluated using Charpy (C) and
      falling-weight (FW) impact tests. METHODS: Bar-shaped (60*6*2mm(3)) and denture
      shaped specimens (2mm) for the C and FD tests, respectively, were prepared with
      Lucitone 550 (L) and Vipi Wave (V) and relined (2mm) using the same material or
      the autopolymerizing relining resins Tokuyama Rebase II (T) and Ufi Gel Hard (U).
      Bulk specimens (60*6*4mm(3)) of all materials (L, V, T and U) were also prepared
      and tested. To evaluate the effect of reinforcement, glass flakes were added to
      the powder of the relining resins T and U (5% by weight). Half of bar-shaped
      (n=320) and half of the denture-shaped specimens (n=480) were subjected to cyclic
      loading (10,000 cycles) before the impact tests. RESULTS: Data were analyzed by
      one-way ANOVAs (alpha=0.05) and revealed that the RI of L and V were comparable
      and higher than those of U and T. Compared to L and V, the RI was increased by
      relining with T and decreased by relining with U. When relining was made using
      the same material (L and V) the RI was maintained. Flexural cyclic loading and
      the incorporation of glass flakes into the resins T and U did not cause any
      significant alteration in the RI. A high correlation between results from C and
      FW tests was observed (r=0.8854). CONCLUSION: Relining may exert effects on the
      RI of L and V denture base resins, which vary according to the relining material
      used. The high correlation between C and FW, suggests that the Charpy test, using
      bar-shaped specimens, can be a simple and reliable method for evaluating factors
      that may influence the RI of denture base polymers.

PMID- 24880568
TI  - Effects of alginate hydrogel cross-linking density on mechanical and biological
      behaviors for tissue engineering.
AB  - An effective cross-linking of alginate gel was made through reaction with calcium
      carbonate (CaCO3). We used human chondrocytes as a model cell to study the
      effects of cross-linking density. Three different pore size ranges of cross
      linked alginate hydrogels were fabricated. The morphological, mechanical, and
      rheological properties of various alginate hydrogels were characterized and
      responses of biosynthesis of cells encapsulated in each gel to the variation in
      cross-linking density were investigated. Desired outer shape of structure was
      maintained when the alginate solution was cross-linked with the applied method.
      The properties of alginate hydrogel could be tailored through applying various
      concentrations of CaCO3. The rate of synthesized GAGs and collagens was
      significantly higher in human chondrocytes encapsulated in the smaller pore
      structure than that in the larger pore structure. The expression of chondrogenic
      markers, including collagen type II and aggrecan, was enhanced in the smaller
      pore structure. It was found that proper structural morphology is a critical
      factor to enhance the performance and tissue regeneration. 

PMID- 24880569
TI  - [Determinants of survival in HIV patients receiving antiretroviral therapy in
      Goma, Democratic Republic of Congo].
AB  - BACKGROUND: The study aimed to identify factors associated with the survival of
      patients receiving antiretroviral therapy. METHODS: A historic cohort of HIV
      patients from two major hospitals in Goma (Democratic Republic of Congo) was
      followed from 2004 to 2012. The Kaplan-Meier method was used to describe the
      probability of survival as a function of time since inclusion into the cohort.
      The log-rank test was used to compare survival curves based on determinants. The
      Cox regression model identified the determinants of survival since treatment
      induction. RESULTS: The median follow-up time was 3.56 years (IQR=2.22-5.39). The
      mortality rate was 40 deaths per 1000 person-years. Male gender (RR: 2.56; 95 %CI
      1.66-4.83), advanced clinical stage (RR: 2.12; 95 %CI 1.15-3.90), low CD4 count
      (CD4 < 50) (RR: 2.05; 95 %CI : 1.22-3.45), anemia (RR: 3.95; 95 %CI 2.60-6.01),
      chemoprophylaxis with cotrimoxazole (RR: 4.29, 95 % CI 2.69-6.86) and period of
      treatment initiation (2010-2011) (RR: 3.34; 95 %CI 1.24-8.98) were statistically
      associated with short survival. CONCLUSION: Initiation of treatment at an early
      stage of the disease with use of less toxic molecules and an increased
      surveillance especially of male patients are recommended to reduce mortality.

PMID- 24880571
TI  - Differential regulation of bladder cancer growth by various glucocorticoids:
      corticosterone and prednisone inhibit cell invasion without promoting cell
      proliferation or reducing cisplatin cytotoxicity.
AB  - PURPOSE: A synthetic glucocorticoid, dexamethasone, was recently shown to inhibit
      bladder cancer cell invasion and metastasis through the glucocorticoid receptor
      (GR) pathway but increased cell proliferation via inhibiting apoptosis
      particularly induced by cisplatin. Therefore, comedication with dexamethasone in
      bladder cancer patients may lead to unfavorable outcomes such as chemoresistance.
      We here look for any glucocorticoids with inhibitory effects on tumor cell
      invasion yet inhibitory or at least no stimulatory effects on cell viability.
      METHODS: The effects of 10 glucocorticoids on cell viability were first assessed
      in three bladder cancer lines. Selected compounds were further assessed for their
      ability in cell viability and apoptosis, with or without cisplatin, as well as in
      cell invasion. RESULTS: Most of the compounds (hydrocortisone, betamethasone,
      flumethasone, triamcinolone, budesonide, fluticasone propionate, and
      fludrocortisone acetate) increased GR-positive cell growth, which was similar to
      or even stronger than the effect of dexamethasone. Nonetheless, two
      glucocorticoids (corticosterone, prednisone) showed only marginal effects on cell
      growth of all the lines tested. They did not significantly reduce the effects of
      cisplatin on cell proliferation or cisplatin-induced apoptosis. Conversely,
      corticosterone, prednisone, and dexamethasone similarly inhibited cell invasion
      and expression of related genes, including MMP-9, VEGF, and IL-6, in GR-positive
      lines. CONCLUSION: Corticosterone and prednisone are suggested to have the
      potential of being harmless, in contrast to dexamethasone, without promoting cell
      proliferation or inhibiting cytotoxic activity of cisplatin, yet beneficial to
      bladder cancer patients via suppressing tumor invasion. Our results are thus
      useful in improving chemotherapy regimens, including optimal glucocorticoids, for
      urothelial carcinoma.

PMID- 24880572
TI  - Incorporating a radiologist in a radiation oncology department: a new model of
      care?
AB  - AIMS: Increasingly complex imaging techniques, such as computed tomography,
      magnetic resonance imaging and positron emission tomography/computed tomography
      scans are being used by radiation oncologists to improve the accuracy of their
      radiotherapy planning contours, despite limited formal training in diagnostic
      imaging. This study aimed to assess whether the availability of an 'in-house'
      radiologist would be beneficial in enhancing the interpretation of oncological
      imaging and accuracy of contouring. MATERIALS AND METHODS: A radiology/oncology
      fellow was based in the oncology department, providing radiological advice on
      diagnostic and planning images, for two sessions per week over a 9 month period.
      Oncology staff were able to book a time slot with the radiologist on a MOSAIQ
      cancer database and record the reason for the consultation and its outcome. The
      radiologist also reviewed the accuracy of the patient's contours for the weekly
      quality assurance audit meetings. RESULTS: The radiologist reviewed 56 scans
      during the 49 consultation sessions. Advice over diagnostic images and target
      volume delineation were the main reasons for the consultations, which resulted in
      a change of practice in 45% of cases, ranging from changing target volumes (25%)
      to carrying out further imaging (20%). For the quality assurance audit meetings,
      the radiologist's review of 99 patients' planning contours resulted in a
      significant change in management in 6% of cases. CONCLUSIONS: This is the first
      study to attempt to formally quantify the clinical benefit of having a dedicated
      'in-house' radiologist within a radiation oncology department, clearly showing
      the valuable impact of such a role.

PMID- 24880570
TI  - Phase 1 dose-escalation study of the PARP inhibitor CEP-9722 as monotherapy or in
      combination with temozolomide in patients with solid tumors.
AB  - PURPOSE: Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear enzyme important in
      DNA repair. PARP-1 activation at points of DNA strand break results in poly(ADP
      ribose) polymer formation, opening the DNA structure, and allowing access of
      other repair enzymes. CEP-9722 inhibits PARP-1 and PARP-2 and is designed to
      potentiate DNA-damaging chemotherapies. METHODS: This dose-escalating phase 1
      study assessed the safety, maximum tolerated dose (MTD), and
      pharmacokinetics/pharmacodynamics of CEP-9722 plus temozolomide in adults with
      solid tumors. Tumor response was also assessed. Participants received a 14-day
      cycle of CEP-9722 (days 1 and 3-5 or days 1-5), followed by 28-day cycles of CEP
      9722 plus temozolomide 150 mg/m(2) on days 1-5. The initial CEP-9722 dose (cohort
      1) was 150 mg/day; dose escalation followed a modified Fibonnaci sequence.
      RESULTS: Twenty-six patients received CEP-9722 150-1,000 mg/day combined with
      temozolomide. Dose-limiting toxicities of asthenia and persistent weight loss at
      1,000 mg/day resulted in 750 mg/day being defined as the MTD and recommended dose
      for further study. Overall, 24 (92 %) patients had treatment-related adverse
      events (TRAEs), mostly grade 1 or 2, with nausea, vomiting, and diarrhea having
      the strongest relation to CEP-9722. Four patients had grade 3 TRAEs (asthenia,
      myositis, diarrhea, and fatigue). Systemic exposure generally increased with
      dosage, with high inter- and intra-patient variability at all doses.
      Pharmacodynamic assessment confirmed PARP inhibition although no dose response
      was apparent. One patient with melanoma achieved a partial response (1,000
      mg/day). CONCLUSIONS: CEP-9722 was adequately tolerated with temozolomide; the
      MTD was 750 mg/day. Only limited clinical activity was observed.

PMID- 24880573
TI  - A decision-making algorithm for recipient vein selection in bipedicle deep
      inferior epigastric artery perforator flap autologous breast reconstruction.
AB  - The bipedicle deep inferior epigastric artery perforator (DIEP) flap allows
      reliable transfer of the entire lower abdominal flap in patients who have a small
      pannus or require a large volume breast reconstruction. Selection of recipient
      vessels for the second pedicle can however, be challenging. We describe our
      experience with a consecutive series of twenty three bipedicle DIEP flaps with
      particular focus on selection of the recipient veins. We demonstrate that with
      judicious selection the internal mammary system can be reliably used as
      recipients for both pedicles with low complication rates. 

PMID- 24880574
TI  - Hydrosurgery, a new therapeutic perspective in early care of giant congenital
      nevi: a preliminary series of four cases.
AB  - BACKGROUND: Congenital melanocytic nevi are present at birth or may appear in the
      first weeks of life. Small and medium-size lesions are relatively common,
      affecting approximately 1% of newborns; large or giant melanocytic nevi occur in
      1/20,000-1/500,000 births. The main concern raised by these lesions is their
      potential risk of degeneration which is strongly size-dependent and estimated in
      the literature between 0% and 40% over a lifetime. Although multiple treatment
      modalities have been described, to date there is no consensus regarding their
      optimal management. PATIENTS AND METHODS: Four neonates (three females and one
      male) presenting giant congenital nevi with a mean age 12 days (7-24 days) were
      referred to our Plastic Surgery department for treatment from 2012 to 2013. All
      patients underwent an alternative dermabrasion procedure with the innovative use
      of hydrosurgery. All procedures were performed under general anaesthesia by the
      same senior operator (Dr. B.Bayet). RESULTS: The mean operating time was
      significantly reduced compared to conventional techniques. No complications were
      observed in the postoperative course. Good final results were obtained in three
      patients after a mean follow-up of respectively 11, 8 and 4 months. The first
      operated neonate showed a complete recurrence of pigmentation of the treated
      areas after 6 months. CONCLUSIONS: The need for early treatment in giant
      congenital nevi is admitted by all. Hydrosurgery is easy to use and allows to
      achieve a selective and symmetric resection with an obvious cleavage plane and
      clean-cut borders. Furthermore, this procedure has convinced us with its speed of
      use, ensuring significant time saving, and therefore less morbidity for the
      neonate. Aesthetic results as well as recurrence rate may be comparable to
      conventional techniques. However, regular follow-up to detect any malignancy is
      necessary.

PMID- 24880575
TI  - Advances in oncologic head and neck reconstruction: systematic review and future
      considerations of virtual surgical planning and computer aided design/computer
      aided modeling.
AB  - BACKGROUND: Mastery of craniomaxillofacial reconstruction has been traditionally
      considered to be learning curve dependent, often with inconsistent results during
      the skill acquisition phase. Until recently, the overall success in bony
      oncologic reconstruction of the craniomaxillofacial skeleton has relied mainly on
      the use of 2D imaging modalities, as well as surgical trial-and-error. Virtual
      surgical planning (VSP) and computer aided design (CAD)/computer aided modeling
      (CAM) are gaining traction in oncologic applications and offers opportunity for
      increased accuracy, improved efficiency, and enhanced outcomes. Its role in
      oncologic head and neck reconstruction has not been formally evaluated. METHODS:
      A systematic review of the current literature was conducted by three independent
      reviewers. Three separate search schemes were utilized to identify cases
      incorporating VSP-CAD/CAM technology in head and neck reconstruction for an
      oncologic indication. Inclusion and exclusion criteria were applied; articles
      that met criteria were evaluated for cohort demographics, osteocutaneous flap
      type and usage, oncologic indication, recipient bone reconstructed, flap
      survival, follow up, VSP technology usage, specific reported benefits of the
      technology, and qualitative and quantitative outcome assessments. RESULTS: The
      systematic literature review yielded 87 articles; of these, 33 met inclusion
      criteria describing a total of 220 cases of oncologic head and neck
      reconstruction incorporating virtual planning technology. Numerous qualitative
      benefits of VSP were reported including increased accuracy of the reconstruction
      (93%), decreased intraoperative time (80%), and ease of use (24%) among others.
      However, quantitative results using survey data or preoperative/postoperative CT
      scan comparisons were given for only 33% (3%, 30% respectively) of cases.
      CONCLUSION: VSP represents an evolving technology that ushers oncological
      craniomaxillofacial reconstruction into a modern era that holds potential to
      advance the field with increased reconstructive accuracy, expedition of the
      surgical phase, and improved outcomes. While qualitative improvements from the
      technology are delineated, specific quantifiable benefits and cost-benefit
      analysis are limited and need to be further investigated.

PMID- 24880576
TI  - Cosmetic websites Scotland: legal or lurid.
AB  - BACKGROUND: The provision of cosmetic interventions and their advertising have
      recently come under intense scrutiny in the wake of the PIP scandal and Keogh
      report. AIM: A study of Scottish websites offering esthetic procedures was
      conducted to determine adherence to the advertising standards and regulations
      currently in place. METHODS: Regulations are provided by the Advertising
      Standards Authority, Committee on Advertising Practice, Independent Healthcare
      Advisory Services and General Medical Council. An Internet search was then
      conducted to search for providers of non-surgical and surgical cosmetic
      procedures. RESULTS: Overall 125 websites were reviewed. 109 local and 16
      national with 17 websites associated with cosmetic surgeons. 26 websites failed
      to adhere to regulations. Failure was related to advertising of POM on the
      homepage or dropdown menu (20), offering enticements inappropriately (6). 26.6%
      of websites did not display qualifications of the practitioners. Only 16.6% of
      websites described the specific and the non-specific side effects of "anti
      wrinkle injections" and only 12.5% mentioned alternative treatments. CONCLUSIONS:
      The majority of websites reviewed adhered to current advertising standards.
      Plastic surgeons provide a small percentage of cosmetic procedures. Greater
      regulation at the point of product entry and of all esthetic practitioners is
      required.

PMID- 24880577
TI  - Early complications, pain, and quality of life after reconstructive surgery for
      abdominal rectus muscle diastasis: a 3-month follow-up.
AB  - AIM: The aim of this study was to evaluate early complications following
      retromuscular mesh repair with those after dual layer suture of the anterior
      rectus sheath in a randomised controlled clinical trial for abdominal rectus
      muscle diastasis (ARD). METHODS: Patients with an ARD wider than 3 cm and
      clinical symptoms related to the ARD were included in a prospective randomised
      study. They were assigned to either retromuscular inset of a lightweight
      polypropylene mesh or to dual closure of the anterior rectus fascia using Quill
      self-locking technology. All patients completed a validated questionnaire for
      pain assessment (Ventral Hernia Pain Questionnaire, VHPQ) and for quality of life
      (SF36) prior to and 3 months after surgery. RESULTS: The most frequently seen
      adverse event was minor wound infection. Of the patients, 14/57 had a superficial
      wound infection; five related to Quill and nine to mesh repair. No deep wound
      infections were reported. Patient rating for subjective muscular improvement
      postoperatively was better in the mesh technique group with a mean of 6.9 (range
      0-10) compared to a mean of 4.8 (range 0-10) in the Quill group (p=0.01). The pre
      and post-operative SF36 scores improved in both groups. CONCLUSIONS: There was
      no significant difference between the two surgical techniques in terms of early
      complications and perceived pain at the 3-month follow-up. Both techniques may be
      considered equally reliable for ARD repair in terms of adverse outcomes during
      the early postoperative phase, even though patients operated with a mesh
      experienced better improvement in muscular strength. ClinicalTrial.gov: 2009/227
      31/3/PE/96.

PMID- 24880578
TI  - Do plastic surgical trainees naturally self-select based on fundamental ability?

PMID- 24880579
TI  - Differential expression of molybdenum transport and assimilation genes between
      two winter wheat cultivars (Triticum aestivum).
AB  - Molybdenum (Mo) is an essential trace element for higher plants. Winter wheat
      cultivar 97003 has a higher Mo efficiency than 97014 under Mo-deficiency stress.
      Mo efficiency is related to Mo uptake, transfer and assimilation in plants.
      Several genes are involved in regulating Mo uptake, transfer and assimilation in
      plants. To obtain a better understanding of the aforementioned difference in Mo
      uptake, we have conducted a hydroponic trail to investigate the expression of
      genes related to Mo uptake, transfer and assimilation in the above two cultivars.
      The results indicate a closed relationship between Mo uptake and TaSultr5.1,
      TaSultr5.2 and TaCnx1 expression, according to a stepwise regression analysis of
      the time course of Mo uptake in the two cultivars. Meanwhile, expression of
      TaSultr5.2 in roots also showed a positive relationship with Mo uptake rates.
      97003 had stronger Mo uptake than 97014 at low Mo-application rates (less than 1
      MUmol Mo L(-1)) due to the higher expression of TaSultr5.2, TaSultr5.1 and TaCnx1
      in roots. On the contrary, Mo uptake of 97003 was weaker than 97014 at high Mo
      application rates (ranging from 5 to 20 MUmol Mo L(-1)), which was related to
      significant down-regulation of TaSultr5.2 and TaCnx1 genes in roots of 97003
      compared to 97014. Therefore, we speculated that the differential-expression
      intensities of TaSultr5.2, TaSultr5.1 and TaCnx1 could be the cause of the
      difference in Mo uptake between the two winter wheat cultivars at low and high Mo
      application levels. 

PMID- 24880580
TI  - Neurocognitive capabilities modulate the integration of evidence in
      schizophrenia.
AB  - Previous studies have demonstrated a cognitive bias in the integration of
      disconfirmatory evidence (BADE) in patients with schizophrenia. This bias has
      been associated with delusions. So far, it is unclear how the integration of
      evidence is associated with neurocognitive capabilities. In the current study, 31
      patients with schizophrenia and 29 healthy controls, matched on age, gender,
      education and premorbid verbal intelligence, underwent a BADE task. Written
      scenarios of three consecutive sentences each were presented, which progressively
      reduced the ambiguity of situations. Participants were asked to rate the
      plausibility of four possible interpretations and adjust their ratings in
      response to the provided sentences. Psychometric rating scales and a
      neuropsychological test battery were applied. Patients displayed a bias in the
      integration of confirmatory, but not disconfirmatory evidence and a liberal
      acceptance of belief formation. Correlation analyses revealed no associations of
      evidence integration with the severity of positive symptoms, but with
      neurocognitive domains, especially with processing speed, executive functioning,
      vigilance and working memory. In conclusion, patients with schizophrenia show a
      bias in evidence integration. Neurocognitive functioning emerged as a modulatory
      factor that should be considered in further research. Studies investigating BADE
      in earlier stages of psychosis will be necessary to reveal causal relationships. 

PMID- 24880581
TI  - Eye movement desensitization and reprocessing therapy in subsyndromal bipolar
      patients with a history of traumatic events: a randomized, controlled pilot
      study.
AB  - Traumatic events are frequent in bipolar patients and can worsen the course of
      the disease. Psychotherapeutic interventions for these events have not been
      studied so far. Twenty DSM-IV bipolar I and II patients with subsyndromal mood
      symptoms and a history of traumatic events were randomly assigned to Eye Movement
      Desensitization and Reprocessing therapy (n=10) or treatment as usual (n=10). The
      treatment group received between 14 and 18 Eye Movement Desensitization and
      Reprocessing sessions during 12 weeks. Evaluations of affective symptoms,
      symptoms of trauma and trauma impact were carried out by a blind rater at
      baseline, 2 weeks, 5 weeks, 8 weeks, 12 weeks and at 24 weeks follow-up. Patients
      in the treatment group showed a statistically significant improvement in
      depressive and hypomanic symptoms, symptoms of trauma and trauma impact compared
      to the treatment as usual group after intervention. This effect was only partly
      maintained in trauma impact at the 24 weeks follow-up visit. One patient dropped
      from Eye Movement Desensitization and Reprocessing group whereas four from the
      treatment as usual group. This pilot study suggests that Eye Movement
      Desensitization and Reprocessing therapy may be an effective and safe
      intervention to treat subsyndromal mood and trauma symptoms in traumatized
      bipolar patients. 

PMID- 24880582
TI  - Association between promoter polymorphism (rs10789970) in 5-hydroxytryptamine
      receptor 3B and poor concentration in schizophrenia.

PMID- 24880583
TI  - (106)Ru plaque brachytherapy for uveal melanoma: factors associated with local
      tumor recurrence.
AB  - PURPOSE: Plaque brachytherapy is a common form of treatment for uveal melanoma,
      and the Collaborative Ocular Melanoma Study (COMS) used (125)I. Recently, (106)Ru
      has been reintroduced for plaque brachytherapy in the United States. We reviewed
      our experience treating uveal melanoma with (106)Ru plaque brachytherapy using
      COMS planning techniques, hypothesizing that we would observe similar outcomes to
      those in the COMS. METHODS AND MATERIALS: Medical records of patients undergoing
      (106)Ru plaque brachytherapy were reviewed retrospectively. Patient, tumor, and
      treatment characteristics were recorded. Outcomes including visual acuity, local
      tumor recurrence, salvage treatment, metastasis, and survival were recorded. Cox
      regression analyses were used to determine factors associated with local tumor
      recurrence and enucleation. RESULTS: Twenty-eight patients were studied. Median
      age was 60 years, and 50% were men. Median tumor base diameter and height were
      9.4 and 2.6 mm, respectively. Ophthalmic complications were rare. Local tumor
      recurrence and enucleation occurred in 13 and 4 patients, respectively. Local
      tumor recurrence was associated with low visual acuity in the tumor-bearing eye,
      posterior tumors, small plaque size, and difference in plaque-tumor diameter of
      <6 mm. Enucleation was associated with low visual acuity and posteriorly located
      tumor. Estimated 5-year rate of death and metastasis was 18.5% and 11.4%,
      respectively. CONCLUSIONS: Among patients treated with (106)Ru plaque
      brachytherapy using COMS planning techniques, we found a greater than expected
      rate of local tumor recurrence. Planning (106)Ru plaque brachytherapy should be
      done carefully at centers that have previously used COMS protocols and (125)I.

PMID- 24880584
TI  - Use of a rectal spacer with low-dose-rate brachytherapy for treatment of prostate
      cancer in previously irradiated patients: Initial experience and short-term
      results.
AB  - BACKGROUND: Salvage brachytherapy in patients with prior pelvic radiation carries
      a risk of rectal injury. Herein, we report our initial experience using a
      hydrogel spacer between the prostate and the rectum during salvage brachytherapy.
      METHODS AND MATERIALS: A total of 11 patients with prostate cancer and prior
      radiotherapy (5 prostate brachytherapy, 2 prostate external beam radiation
      therapy [EBRT], and 4 rectal cancer EBRT) received (125)I brachytherapy after
      attempted placement of 10cc of a diluted hydrogel spacer between the prostate and
      rectum. RESULTS: Spacing was achieved in 8 of the 11 (73%) patients but was not
      possible in 3 (1 prior brachytherapy and 2 prior EBRT) owing to fibrosis and
      adhesions. For the 8 patients in whom spacing was accomplished, the median space
      between the prostate and rectum was 10.9mm (prior EBRT) vs. 7.7mm (prior
      brachytherapy), p=0.048. Median followup was 15.7 months. One patient developed a
      prostato-rectal fistula requiring a diverting colostomy. The 16-month estimate of
      late Grade 3 or 4 gastrointestinal or genitourinary toxicity was 26%. One patient
      developed lymph node-positive recurrence. The 16-month prostate-specific antigen
      failure-free survival rate was 89%. Compared with baseline, Expanded Prostate
      Cancer Index Composite for Clinical Practice urinary quality of life (QoL) was
      significantly worse at 3 and 6 months but not significantly worse by 1 year.
      There were no significant changes throughout the study period in bowel or sexual
      QoL. CONCLUSION: Hydrogel spacer placements may be feasible in most patients with
      prior pelvic radiation. Further followup is needed to determine whether spacer
      placement will produce long-term improvements in toxicity or QoL.

PMID- 24880585
TI  - Experimental and Monte Carlo dosimetric characterization of a 1 cm (103)Pd
      brachytherapy source.
AB  - PURPOSE: To determine the in-air azimuthal anisotropy and in-water dose
      distribution for the 1 cm length of a new elongated (103)Pd brachytherapy source
      through both experimental measurements and Monte Carlo (MC) simulations. Measured
      and MC-calculated dose distributions were used to determine the American
      Association of Physicists in Medicine Task Group No. 43 (TG-43) dosimetry
      parameters for this source. METHODS AND MATERIALS: The in-air azimuthal
      anisotropy of the source was measured with a NaI scintillation detector and was
      simulated with the MCNP5 radiation transport code. Measured and MC results were
      normalized to their respective mean values and then compared. The source dose
      distribution was determined from measurements with LiF:Mg,Ti thermoluminescent
      dosimeter (TLD) microcubes and MC simulations. TG-43 dosimetry parameters for the
      source, including the dose-rate constant, Lambda, two-dimensional anisotropy
      function, F(r, theta), and line-source radial dose function, gL(r), were
      determined from the TLD measurements and MC simulations. RESULTS: NaI
      scintillation detector measurements and MC simulations of the in-air azimuthal
      anisotropy of the source showed that >=95% of the normalized values for each
      source were within 1.2% of the mean value. TLD measurements and MC simulations of
      Lambda, F(r, theta), and gL(r) agreed to within the associated uncertainties.
      CONCLUSIONS: This new (103)Pd source exhibits a high level of azimuthal symmetry
      as indicated by the measured and MC-calculated results for the in-air azimuthal
      anisotropy. TG-43 dosimetry parameters for the source were determined through TLD
      measurements and MC simulations.

PMID- 24880586
TI  - Response to Drs Patil and D'souza.

PMID- 24880587
TI  - Response to Drs Rogers, Hayes, and Demanes.

PMID- 24880588
TI  - Diagnostic value of microRNA-21 in the diagnosis of lung cancer: evidence from a
      meta-analysis involving 11 studies.
AB  - Molecular biomarkers that can be detected in easily accessible body fluids have
      been proposed as non-invasive, cost-effective, and useful tools for cancer
      diagnosis. Recently, extensive research has explored the involvement of the
      aberrant expression of microRNA-21 (miRNA-21, miR-21) in lung cancer.
      Inconsistent results, however, have prevented its widespread use in diagnosis. In
      light of this situation, our meta-analysis aimed to systematically determine
      whether aberrant miR-21 expression can distinguish patients with lung cancer from
      cancer-free controls with a high level of diagnostic accuracy. A comprehensive
      literature search for relevant studies published before December 23, 2013 was
      conducted in the MEDLINE, EMBASE, the Cochrane Library, and three Chinese
      databases. The pooled sensitivity, specificity and other parameters were used to
      assess the overall performance of miR-21-based assays. Statistical analysis was
      conducted using the STATA 11.0 software. Eleven research articles involving 676
      patients with lung cancer and 529 healthy controls were considered eligible for
      inclusion in the present meta-analysis. The following summary parameters were
      calculated from all the included studies: sensitivity of 0.66 (95 % confidence
      interval [CI]: 0.57-0.74), specificity of 0.82 (95 % CI: 0.74-0.88), positive
      likelihood ratio (PLR) of 3.70 (95 % CI: 2.50-5.60), negative likelihood ratio
      (NLR) of 0.42 (95 % CI: 0.32-0.54); diagnostic odds ratio (DOR) of 9.00 (95 % CI:
      5.00-16.00), and area under the curve (AUC) of 0.81 (95 % CI: 0.77-0.84). In
      addition, we added two pre-specified covariates (ethnicity and specimen types) to
      the bivariate model to assess their impact on the diagnostic value of miR-21 for
      lung cancer. Similar results were also observed in subgroup analyses, indicating
      a relatively low level of accuracy. The current meta-analysis indicates that a
      single miR-21 may not be sufficient to identify lung cancer and that more miRNAs
      should be used to detect lung carcinoma.

PMID- 24880589
TI  - OLC1 is overexpressed in breast cancer and its expression correlates with poor
      patient survival.
AB  - The overexpressed in lung cancer 1 (OLC1) has been demonstrated to be associated
      with numerous biological and pathological processes. However, the role of OLC1 in
      breast cancer has not been thoroughly elucidated. The purpose of this study was
      to assess OLC1 expression and to explore its contribution to the breast cancer.
      Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR)
      was conducted to detect OLC1 messenger RNA (mRNA) expression in 45 pairs of fresh
      frozen breast cancer tissues and corresponding noncancerous tissues.
      Immunohistochemistry was performed to detect the expression of OLC1 in 145 breast
      cancer tissues. The relationship between the expression of OLC1 and
      clinicopathological characteristics and prognosis was statistically analyzed. We
      found that the expression levels of OLC1 mRNA and protein in breast cancer
      tissues were significantly higher than those in adjacent noncancerous tissues (P
      < 0.001). In addition, OLC1 expression was significantly correlated with tumor
      size (P = 0.034), grade (P = 0.015), stage (P < 0.001), and lymph node metastases
      (P = 0.028). Kaplan-Meier survival analysis showed that a high expression level
      of OLC1 resulted in a significantly poor prognosis of breast cancer patients.
      Further, Cox multivariate analysis indicated that OLC1 expression level was an
      independent prognostic factor for the overall survival rate of breast cancer
      patients. These findings provide evidence that a high expression level of OLC1
      serves as a biomarker for poor prognosis for breast cancer. Thus, we speculate
      that OLC1 may be a potential target of antiangiogenic therapy for breast cancer.

PMID- 24880590
TI  - MicroRNAs as novel biomarkers for pancreatic cancer diagnosis: a meta-analysis
      based on 18 articles.
AB  - Dysregulated microRNAs (miRNAs) have been reported to be associated with
      pancreatic cancer (PaC), suggesting that they may serve as useful novel
      diagnostic biomarkers for PaC. Various studies have been performed to investigate
      the diagnostic value of miRNAs for PaC but have obtained conflicting results.
      Therefore, this meta-analysis aims to comprehensively and quantitatively evaluate
      the potential diagnostic value of miRNAs for PaC. We systematically searched
      PubMed, Embase, Google Scholar, Cochrane Library, and Chinese National Knowledge
      Infrastructure for publications concerning the diagnostic value of miRNAs for PaC
      without language restriction. The quality of each study was scored using the
      revised Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). The summary
      receiver operator characteristic curve and other parameters were applied to check
      the overall test performance. Heterogeneity was tested with the I (2) test and
      publication bias was tested with the Deek's funnel plot asymmetry test. This meta
      analysis included 18 articles with a total of 2,036 patients and 1,444 controls.
      The pooled sensitivity was 82 % (95 % CI, 78-86 %); the specificity was 77 % (95
      % CI, 73-81 %); the PLR was 3.6 (95 % CI, 3.0-4.4); the NLR was 0.23 (95 % CI,
      0.18-0.29); the DOR was 16 (95 % CI, 10-24); and the AUC was 0.86 (95 % CI, 0.83
      0.89). Subgroups analyses were also performed and revealed that there were
      significant differences between some subgroups: the multiple-miRNAs profiling
      based assays, non-blood-based assays, and healthy control-based studies all
      showed higher accuracies in diagnosing PaC than that of their counterparts. This
      meta-analysis suggests that the use of miRNAs has potential diagnostic value with
      a relatively high sensitivity and specificity for PaC, particularly the use of
      multiple miRNAs for discriminating PaC patients from healthy individuals. More
      prospective studies on the diagnostic value of miRNAs for PaC are needed in the
      future.

PMID- 24880591
TI  - Epithelial to mesenchymal transition inducing transcription factors and
      metastatic cancer.
AB  - The epithelial to mesenchymal transition (EMT) is an important step for the
      developmental process. Recent evidences support that EMT allows the tumor cells
      to acquire invasive properties and to develop metastatic growth characteristics.
      Some of the transcription factors, which are actively involved in EMT process,
      have a significant role in the EMT-metastasis linkage. A number of studies have
      reported that EMT-inducing transcription factors (EMT-TFs), such as Twist, Snail,
      Slug, and Zeb, are directly or indirectly involved in cancer cell metastasis
      through a different signaling cascades, including the Akt, signal transducer and
      activator of transcription 3 (STAT3), mitogen-activated protein kinase (MAPK) and
      Wnt pathways, with the ultimate consequence of the downregulation of E-cadherin
      and upregulation of metastatic proteins, such as N-cadherin, vimentin, matrix
      metalloproteinase (MMP)-2, etc. This review summarizes the update information on
      the association of EMT-TFs with cancer metastasis and the possible cancer
      therapeutics via targeting the EMT-TFs. 

PMID- 24880593
TI  - Polycyclic aromatic hydrocarbons (PAHs) in wetland soils under different land
      uses in a coastal estuary: toxic levels, sources and relationships with soil
      organic matter and water-stable aggregates.
AB  - The concentrations of 16 polycyclic aromatic hydrocarbons (PAHs) were determined
      in the soils from industrial, wharf, cropland, milldam and natural wetland sites
      to characterize their distributions, toxic levels and possible sources in the
      Pearl River Estuary and identify their relationships with soil organic matter
      (SOM) and water-stable aggregates (WSAs). Our results indicate that the average
      concentration of total PAHs in this region reached a moderate pollution level,
      which was higher than that in other larger estuaries in Asia. The average level
      of total PAHs in industrial soils was 1.2, 1.5, 1.6 and 2.3 times higher than
      those in soils from wharf, cropland, milldam and natural wetland sites,
      respectively. Greater accumulation of PAHs occurred in the middle and/or bottom
      soil layers where 3-ring PAHs were dominant. Industrial soils also exhibited the
      highest toxic levels with the highest toxic equivalent concentrations of PAHs,
      followed by wharf and milldam soils, and the cropland and wetland soils had the
      lowest toxicity. The diagnostic ratios suggested that PAHs primarily originated
      from biomass and coal combustion at industrial and milldam sites, and petroleum
      combustion was determined to be the primary source of PAHs at the wharf, cropland
      and wetland sites. Both 3-ring and 4-ring PAHs in the milldam and wharf soils
      were significantly positively correlated with the SOM, whereas the 4,5,6-ring
      PAHs and total PAHs in industrial soils and the 2-ring PAHs in cropland soils
      were significantly negatively correlated with the SOM. In addition, large WSAs
      also exhibited a significant positive correlation with PAHs. 

PMID- 24880594
TI  - Investigation of waste incineration of fluorotelomer-based polymers as a
      potential source of PFOA in the environment.
AB  - In light of the widespread presence of perfluorooctanoic acid (PFOA) in the
      environment, a comprehensive laboratory-scale study has developed data requested
      by the U.S. Environmental Protection Agency (EPA) to determine whether municipal
      and/or medical waste incineration of commercial fluorotelomer-based polymers
      (FTBPs) at end of life is a potential source of PFOA that may contribute to
      environmental and human exposures. The study was divided into two phases (I and
      II) and conducted in accordance with EPA Good Laboratory Practices (GLPs) as
      described in the quality assurance project plan (QAPP) for each phase. Phase I
      testing determined that the PFOA transport efficiency across the thermal reactor
      system to be used in Phase II was greater than 90%. Operating at 1000 degrees C
      over 2s residence time with 3.2-6.6mgdscm(-1) hydrogen fluoride (HF), corrected
      to 7% oxygen (O2), and continuously monitored exhaust oxygen of 13%, Phase II
      testing of the FTBP composites in this thermal reactor system yielded results
      demonstrating that waste incineration of fluorotelomer-based polymers does not
      result in the formation of detectable levels of PFOA under conditions
      representative of typical municipal waste combustor (MWC) and medical waste
      incinerator (MWI) operations in the U.S. Therefore, waste incineration of these
      polymers is not expected to be a source of PFOA in the environment. 

PMID- 24880595
TI  - Persistent halogenated compounds in captive Chinese alligators (Alligator
      sinensis) from China.
AB  - While a number of studies have reported residual levels of persistent halogenated
      compounds (PHCs) in crocodilia, there is still a dearth of information on the
      Chinese alligator, a critically endangered crocodilian species. In the present
      study, several PHCs, including polybrominated diphenyl ethers (PBDEs),
      polychlorinated biphenyls (PCBs), and dichlorodiphenyltrichloroethane and its
      metabolites (DDTs), were detected in the adult tissues, neonates, and eggs of
      captive Chinese alligators from China. The concentrations of SigmaPBDEs,
      SigmaPCBs, and SigmaDDTs in Chinese alligators ranged from 0.11 to 16.1, 1.12 to
      22.2, and 6.03 to 1020ngg(-1) wet weight, respectively, with higher levels of
      SigmaPCBs and SigmaDDTs in the neonates and eggs than in muscle tissues. The
      SigmaDDT residues in the studied Chinese alligators were at the high end of
      reported ranges from crocodilia around the world, and some results exceeded
      levels known to cause a female-biased sex ratio in crocodilians. 

PMID- 24880592
TI  - Prenatal exposure to organochlorine pesticides and infant birth weight in China.
AB  - In utero exposure to organochlorine pesticides (OCPs) is thought to be
      potentially harmful to fetal development. We aimed to investigate the
      associations of maternal and cord serum OCPs levels with infant birth weight in
      China. In this study, we measured serum levels of 18 OCPs in 81 mother-infant
      pairs, including DDT, hexachlorocyclohexanes (BHC), hexachlorobenzene (HCB),
      heptachlors, chlordanes, endosulfan-I, and mirex using a high-resolution-gas
      chromatography with high-resolution-mass-spectrometry method. We found that p,p'
      DDE and beta-BHC had the highest detection rate in both maternal and cord blood
      serum (97.2% and 96.7%, respectively), followed by HCB (93.0%, 51.7%), p,p'-DDT
      (88.7%, 36.7%), and p,p'-DDD (83.1%, 60.0%). Among all OCPs, the concentration of
      p,p'-DDE was the highest (mothers geometric mean (GM): 203.54ngg(-1), newborns
      GM: 116.14ngg(-1)), followed by HCB (70.62ngg(-1), 65.16ngg(-1)), and beta-BHC
      (67.67ngg(-1), 33.39ngg(-1)). Multiple linear regression analyses showed that
      each 1ngg(-1) increment of cord serum p,p'-DDE, total DDT, and beta-BHC was
      associated with a 0.10g, 0.10g, and 0.92g decrease in infant birth weight,
      respectively, and as the cord serum concentrations of p,p'-DDT, p,p'-DDD, HCB and
      mirex increased, the infant birth weight was also decreased, although the
      associations were not statistically significant due to the relatively small
      sample size. These results suggest that p,p'-DDE, beta-BHC, and HCB were the
      predominant OCPs in the serum of Chinese pregnant women and cord blood of their
      newborns. Prenatal exposure to DDT, beta-BHC, HCB, and mirex were associated with
      a decrease in birth weight, but these results need validation in larger sample
      sized studies. 

PMID- 24880596
TI  - Modelling the influence of climate change on the chemical concentrations in the
      Baltic Sea region with the POPCYCLING-Baltic model.
AB  - The effect of projected future changes in temperature, wind speed, precipitation
      and particulate organic carbon on concentrations of persistent organic chemicals
      in the Baltic Sea regional environment is evaluated using the POPCYCLING-Baltic
      multimedia chemical fate model. Steady-state concentrations of hypothetical
      perfectly persistent chemicals with property combinations that encompass the
      entire plausible range for non-ionizing organic substances are modelled under two
      alternative climate change scenarios (IPCC A2 and B2) and compared to a baseline
      climate scenario. The contributions of individual climate parameters are deduced
      in model experiments in which only one of the four parameters is changed from the
      baseline scenario. Of the four selected climate parameters, temperature is the
      most influential, and wind speed is least. Chemical concentrations in the Baltic
      region are projected to change by factors of up to 3.0 compared to the baseline
      climate scenario. For chemicals with property combinations similar to legacy
      persistent organic pollutants listed by the Stockholm Convention, modelled
      concentration ratios between two climate change scenarios and the baseline
      scenario range from factors of 0.5 to 2.0. This study is a first step toward
      quantitatively assessing climate change-induced changes in the environmental
      concentrations of persistent organic chemicals in the Baltic Sea region. 

PMID- 24880597
TI  - Polybrominated diphenyl ethers (PBDEs) in English freshwater lakes, 2008-2012.
AB  - Concentrations of tri-to-hexa-BDEs were determined in water samples taken from 9
      English lakes on 13 occasions between April 2008 and February 2012. Across all
      sites, concentrations of SigmaBDEs in individual samples ranged from 9.2 to
      171.5pgL(-)(1), with an average of 61.9pgL(-)(1). Notwithstanding the far greater
      use of the Penta-BDE commercial formulation in the USA, concentrations in this
      study are comparable to the limited data available for the Great Lakes. PBDE
      concentrations showed no evidence of a decline at any monitored location over the
      study period. This may be because this study commenced 4years after the
      introduction of restrictions on the Penta- and Octa-BDE formulations. While
      concentrations normalised to water volume at the different locations were
      statistically indistinguishable; significant spatial variation was apparent when
      the data were normalised to total suspended solids (TSS) content. However, this
      spatial variation was not correlated with factors such as population density and
      lake catchment area, suggesting that concentrations of PBDEs in lake water in
      this study are a complex integral of numerous factors. BDE-47:99 ratios and
      concentrations of SigmaBDEs respectively decreased and increased significantly
      with increasing TSS content. As TSS content was elevated in colder compared with
      warmer periods, such seasonal variation in TSS content appears a major
      contributor to the observed elevation of SigmaBDE concentrations in colder
      periods, and higher BDE-47:99 ratios in warmer periods. 

PMID- 24880598
TI  - "Intrinsic" elimination rate and dietary intake estimates for selected indicator
      PCBs: toxicokinetic modeling using serial sampling data in US subjects, 2005
      2010.
AB  - Changes in measured concentrations of persistent compounds such as
      polychlorinated biphenyls (PCBs) in an individual over time reflect not only
      intrinsic elimination rates but also any ongoing intake of the compounds and
      changes in the volume of distribution. Thus, "apparent" elimination rates
      calculated from data on changes in serum lipid-adjusted concentration may over-
      or under-estimate the "intrinsic" elimination rates for such compounds. Serum PCB
      concentrations were measured in 43 individuals approximately 5years apart.
      Changes in measured concentrations and body weights were used to estimate mass
      based apparent elimination rates. The changes in estimated body mass of PCBs 105,
      118, 138, 153, and 180 were input into a simple first-order model employing
      previously estimated intrinsic elimination rates to estimate congener-specific
      average dietary intake rates over the period between samples. Calculated median
      dietary intakes were compared to previous estimates. Intrinsic elimination rates
      were adjusted for two congeners. The analyses support central tendencies of
      intrinsic elimination rates of approximately 5years for PCBs 105 and 118, 11years
      for PCB 138, 14.4years for PCB 153, and 20years or more for PCB 180. Estimated
      dietary intakes for this population and time period depend on the assumed
      intrinsic elimination rates and range from 0.1ngkg(-1)d(-1) for PCB 105 to
      approximately 1-2ngkg(-1)d(-1) for PCB 180. Estimated body burdens of PCB 180
      changed very little over the five-year period, suggesting near steady-state
      exposure levels. As a result, estimates for both elimination half-life and
      ongoing intake rates for this congener are highly uncertain. 

PMID- 24880599
TI  - Assessment of the local role of a steel making plant by POPs deposition
      measurements.
AB  - Atmospheric depositions of polychlorinated dibenzo-p-dioxins and dibenzofurans
      (PCDD/Fs) and polychlorinated biphenyls (PCBs) were monitored at three sites in
      the vicinity of a steel making plant, located in an Italian alpine valley. A high
      variability in the deposition of PCDD/Fs was observed. The influence of the plant
      was noticeable at two of the sampling sites. However, as the congener profiles
      demonstrated, wood burning for domestic heating is an additional source of
      PCDD/Fs for the area under investigation, and this interferes with the
      characterization of the emissions from the steel plant. The influence of the
      plant, in terms of PCDD/F deposition, was not noticeable at the most distant site
      (2km), where an extremely high peak of PCDD/F deposition was measured during the
      period from 12 January-22 February 2012. The comparison between the congener
      distribution of PCDD/Fs observed in this sample and the fingerprints of different
      sources could justify the attribution of this anomalous peak to a possible
      episode of domestic waste combustion. In order to find a better correlation
      between the deposition to soil and emissions from the plant, the congener
      distribution of PCBs was studied. The PCB profiles observed at the three sites
      well reproduced the average profile found in samples of ash retained by the bag
      filter of the plant. Thus the monitoring of PCB deposition is an interesting
      starting point to calibrate dispersion models to assess the impact of steel
      making activities. 

PMID- 24880600
TI  - Autochthonous ascomycetes in depollution of polychlorinated biphenyls
      contaminated soil and sediment.
AB  - We investigated the capacity of a consortium of ascomycetous strains, Doratomyces
      nanus, Doratomyces purpureofuscus, Doratomyces verrucisporus, Myceliophthora
      thermophila, Phoma eupyrena and Thermoascus crustaceus in the mycoremediation of
      historically contaminated soil and sediment by polychlorinated biphenyls (PCBs).
      Analyses of 15 PCB concentrations in three mesocosms containing soil from which
      the fungal strains had previously been isolated, revealed significant PCB
      depletions of 16.9% for the 6 indicator PCBs (i-PCBs) and 18.7% for the total 15
      PCBs analyzed after 6months treatment. The degradation rate did not statistically
      vary whether the soil had been treated with non-inoculated straw or colonized
      straw or without straw and inoculated with the consortium of the six strains.
      Concerning the sediment, we evidenced significant depletions of 31.8% for the 6 i
      PCBs and 33.3% for the 15 PCB congeners. The PCB depletions affected most of the
      15 PCBs analyzed without preference for lower chlorinated congeners. Bioaugmented
      strains were evidenced in different mesocosms, but their reintroduction, after
      six months treatment, did not improve the rate of PCB degradation, suggesting
      that the biodegradation could affect the bioavailable PCB fraction. Our results
      demonstrate that the ascomycetous strains potentially adapted to PCBs may be
      propitious to the remediation of PCB contaminated sites. 

PMID- 24880601
TI  - Biodegradation of decabromodiphenyl ether (BDE-209) by white-rot fungus Phlebia
      lindtneri.
AB  - This work investigated degradation of decabromodiphenyl ether (BDE-209) by
      Phlebia lindtneri under the influence of glucose and heavy metals (Cd(2+), Cu(2+)
      or Pb(2+)). The results showed that adding glucose could markedly promote BDE-209
      biodegradation. In the absence of heavy metals, 77.3% BDE-209 was degraded within
      30d when dealing with 20mgL(-1) BDE-209. BDE-209 degradation was stimulated at
      low concentrations of Cu and Pb, whereas inhibited at higher levels of metals.
      The culture pH tended to decrease with time. Adding lower concentrations of Cu
      (?5.0mgL(-1)) enhanced laccase activity. No stimulatory effect was observed on
      laccase activity in the presence of Cd or Pb. Ecotoxicity in the culture
      significantly increased at the late stage of the experiment. Bromine ions were
      released and the debromination rate of BDE-209 was much lower than its
      degradation rate. The fungus could degrade BDE-209 through debromination,
      hydroxylation, and ring-opening reactions. 

PMID- 24880602
TI  - Distribution and pollutant load of hexabromocyclododecane (HBCD) in sewage
      treatment plants and water from Japanese Rivers.
AB  - Hexabromocyclododecane diastereoisomers (alpha-, beta-, gamma-, delta-, and
      epsilon-HBCD) were investigated in river water, sewage influent, and sewage
      effluent from the Yodo River basin, Japan. The mean annual values of HBCDs ranged
      from 0.19 to 14ngL(-1) in river water. We observed that the concentrations of
      HBCDs in the brackish water area were low compared with that in the fresh water
      area. It was implied that, when the flow of the river stagnated in the estuarine
      area, HBCDs settled with suspended matter because of their hydrophobic character.
      In the sewage treatment plants, HBCDs ranged from 16 to 400ngL(-1) in sewage
      influent, whereas they ranged from 0.39 to 12ngL(-1) in sewage effluent. Over 90%
      of HBCDs were removed from the wastewater in the sewage treatment plants. By
      using these results, we estimated the pollutant load of HBCDs that flows into
      Osaka Bay from the study area. It was estimated that approximately 15kg of HBCDs
      flow into Osaka Bay from the study area in a year. This value is five orders of
      magnitude lower than the 2010 market demand for HBCDs (3019 metrictons) in Japan.

PMID- 24880603
TI  - Fungal enzyme production and biodegradation of polychlorinated dibenzo-p-dioxins
      and dibenzofurans in contaminated sawmill soil.
AB  - The current treatment method for PCDD/F-contaminated soil, which fulfils the
      requirements for POP soils, is incineration at high temperature. In this study,
      we investigated if bioaugmentation with fungal inoculum or treatment with
      manganese peroxidase (MnP) enzyme preparation could be used instead. The main
      source of PCDD/F contamination in Finland has been the national production and
      use of a chlorophenol containing wood preservative, which contained PCDD/Fs as
      impurities. Therefore, historically contaminated soils from three sawmill sites
      were used in the experiments. In bioaugmentation experiments with living fungal
      mycelia, enzyme production, CO2 production and degradation of chlorinated dioxins
      were measured. When cell free MnP preparation was added to the soil, it was
      likewise important to follow how enzyme activity was maintained in the soil. As a
      result of this study, we showed that fungi were able to efficiently degrade
      PCDD/F, but surprisingly the addition of MnP preparation did not have any effect
      to the PCDD/F concentration. However, substantial amounts of MnP activity were
      found in the soil still after 10d of incubation. Treatment with either Stropharia
      rugosoannulata or Phanerochaete velutina resulted in 62-64% decrease in WHO-TEQ
      value in 3months. One critical factor for efficient biodegradation was strong
      growth of fungal mycelia in non-sterile contaminated soil. 

PMID- 24880605
TI  - Recurrent laryngeal nerve palsy and substernal goiter. An Italian multicenter
      study.
AB  - The aim of this retrospective multicenter study was to verify whether the
      substernal goiter and the type of surgical access could be risk factors for
      recurrent laryngeal nerve palsy during total thyroidectomy. Between 1999-2008,
      14,993 patients underwent total thyroidectomy. Patients were divided into three
      groups: group A (control; n=14.200, 94.7%), cervical goiters treated through
      collar incision; group B (n=743, 5.0%) substernal goiters treated by cervical
      approach; group C (n=50, 0.3%) in which a manubriotomy was performed. Transient
      and permanent unilateral palsy occurred significantly more frequently in B+C vs.
      A (P<=.001) and in B vs. A (P<=.001). Transient bilateral palsy was significantly
      more frequent in B+C vs. A (P<=.043) and in C vs. A (P<=.016). Permanent
      bilateral palsy was significantly more frequent in B+C vs. A (P<=.041), and in B
      vs. A (P<=.037). Extension of the goiter into the mediastinum was associated to
      increased risk of recurrent nerve palsy during total thyroidectomy. 

PMID- 24880606
TI  - [Volar dislocation of the fifth carpometacarpal joint: a case report].
AB  - Pure carpo-metacarpal dislocations without any fracture are rare, their volar
      component is exceptional. Untreated injuries can result in instability and early
      articular degeneration. We report a 72-year-old female patient who underwent an
      isolated closed volar dislocation of her fifth finger carpo-metacarpal joint
      after a fall. The clinical examination showed a 10 degrees -defect in rotation
      with limited adduction (radial deviation). The X-rays showed a gap between the
      base of the fourth and the fifth metacarpal bones with volar dislocation of the
      base of the fifth carpometacarpal joint. The dislocation was successfully treated
      by closed reduction maintained with two K-wires. Immobilisation of the joint was
      applied for 6 weeks. At 2 years follow-up evaluation, the patient was pain free
      with no clinico-radiological evidence of instability and had returned to her
      previous level of activity.

PMID- 24880604
TI  - HLA alleles associated with the adaptive immune response to smallpox vaccine: a
      replication study.
AB  - We previously reported HLA allelic associations with vaccinia virus (VACV)
      induced adaptive immune responses in a cohort of healthy individuals (n = 1,071
      subjects) after a single dose of the licensed smallpox (Dryvax) vaccine. This
      study demonstrated that specific HLA alleles were significantly associated with
      VACV-induced neutralizing antibody (NA) titers (HLA-B*13:02, *38:02, *44:03,
      *48:01, and HLA-DQB1*03:02, *06:04) and cytokine (HLA-DRB1*01:03, *03:01, *10:01,
      *13:01, *15:01) immune responses. We undertook an independent study of 1,053
      healthy individuals and examined associations between HLA alleles and measures of
      adaptive immunity after a single dose of Dryvax-derived ACAM2000 vaccine to
      evaluate previously discovered HLA allelic associations from the Dryvax study and
      determine if these associations are replicated with ACAM2000. Females had
      significantly higher NA titers than male subjects in both study cohorts [median
      ID50 discovery cohort 159 (93, 256) vs. 125 (75, 186), p < 0.001; replication
      cohort 144 (82, 204) vs. 110 (61, 189), p = 0.024]. The association between the
      DQB1*03:02 allele (median ID50 discovery cohort 152, p = 0.015; replication
      cohort 134, p = 0.010) and higher NA titers was replicated. Two HLA associations
      of comparable magnitudes were consistently found between DRB1*04:03 and
      DRB1*08:01 alleles and IFN-gamma ELISPOT responses. The association between the
      DRB1*15:01 allele with IFN-gamma secretion was also replicated (median pg/mL
      discovery cohort 182, p = 0.052; replication cohort 203, p = 0.014). Our results
      suggest that smallpox vaccine-induced adaptive immune responses are significantly
      influenced by HLA gene polymorphisms. These data provide information for
      functional studies and design of novel candidate smallpox vaccines.

PMID- 24880607
TI  - First metacarpal resurfacing with polyvinyl alcohol implant in osteoarthritis:
      preliminary study.
AB  - Osteoarthritis of first carpometacarpal (CMC) joint is a condition that is
      frequently encountered in hand surgery. If conservative treatment fails, several
      surgical procedures are available ranging from arthroscopic debridement to total
      joint arthroplasty. This study focuses on a new resurfacing technique for the
      base of the first metacarpal using a polyvinyl alcohol hydrogel implant. Our
      preliminary study found good clinical outcomes and no inflammatory reaction after
      a follow-up of 30 months. However prospective studies with a longer follow-up and
      more patient are needed to confirm these results.

PMID- 24880608
TI  - Treatment of solutions containing nonylphenol ethoxylate by
      photoelectrooxidation.
AB  - In this work the photoelectrooxidation (PEO) was applied in the treatment of a
      solution containing nonylphenol ethoxylate surfactant (NP4EO). The use of
      different lamps (125 and 250 W), current density (5 and 10 mA cm(-2)) and
      treatment time (0, 60, 120, 180 and 240 min) were investigated. The samples were
      characterized by UV/Vis, total organic carbon (TOC), gas chromatography
      associated to mass spectroscopy (GC/MS) and ecotoxicity. The reaction kinetics
      were calculated and the light flux and pH were measured. The results of analysis
      by UV/Vis show that there is degradation of nonylphenol ethoxylated in the
      treatment time of 240 min for all configurations, and the configurations that
      used a 250 W lamp and a current density of 10 mA cm(-2) obtained better results,
      with a reduction of 83% in TOC, indicating a high mineralization of the
      surfactant. It was further found in the GC/MS that the configurations that used
      the 125 W lamp promoted a smaller incident light flux on the solution, and,
      regardless of the applied current density, it was generated the reaction
      intermediate nonylphenol, more toxic than the parent compound. The opposite can
      be observed when a 250 W lamp was used, which produced a higher incident light
      flux. Based on the degradation products detected, a simplified mechanism for
      degradation of nonylphenol ethoxylate was proposed. Although a treatment time of
      240 min with photoelectrooxidation with different configurations was not
      effective in the complete mineralization of the compound, a promising process was
      developed with the treatment using a lamp of 250 W and a current density of 10 mA
      cm(-2), which generated a solution with less toxicity than the original one.

PMID- 24880609
TI  - Development of an energy-saving anaerobic hybrid membrane bioreactors for 2
      chlorophenol-contained wastewater treatment.
AB  - A novel energy-saving anaerobic hybrid membrane bioreactor (AnHMBR) with mesh
      filter, which takes advantage of anaerobic membrane bioreactor and fixed-bed
      biofilm reactor, is developed for low-strength 2-chlorophenol (2-CP)-contained
      wastewater treatment. In this system, the anaerobic membrane bioreactor is
      stuffed with granular activated carbon to construct an anaerobic hybrid fixed-bed
      biofilm membrane bioreactor. The effluent turbidity from the AnHMBR system was
      low during most of the operation period, and the chemical oxygen demand and 2-CP
      removal efficiencies averaged 82.3% and 92.6%, respectively. Furthermore, a low
      membrane fouling rate was achieved during the operation. During the AnHMBR
      operation, the only energy consumption was for feed pump. And a low energy demand
      of 0.0045-0.0063kWhm(-3) was estimated under the current operation conditions.
      All these results demonstrated that this novel AnHMBR is a sustainable technology
      for treating 2-CP-contained wastewater. 

PMID- 24880610
TI  - Impact of esterified bacteriochlorophylls on the biogenesis of chlorosomes in
      Chloroflexus aurantiacus.
AB  - A chlorosome is an antenna complex located on the cytoplasmic side of the inner
      membrane in green photosynthetic bacteria that contains tens of thousands of self
      assembled bacteriochlorophylls (BChls). Green bacteria are known to incorporate
      various esterifying alcohols at the C-17 propionate position of BChls in the
      chlorosome. The effect of these functional substitutions on the biogenesis of the
      chlorosome has not yet been fully explored. In this report, we address this
      question by investigating various esterified bacteriochlorophyll c (BChl c)
      homologs in the thermophilic green non-sulfur bacterium Chloroflexus aurantiacus.
      Cultures were supplemented with exogenous long-chain alcohols at 52  degrees C
      (an optimal growth temperature) and 44  degrees C (a suboptimal growth
      temperature), and the morphology, optical properties and exciton transfer
      characteristics of chlorosomes were investigated. Our studies indicate that at 44
      degrees C Cfl. aurantiacus synthesizes more carotenoids, incorporates more BChl
      c homologs with unsaturated and rigid polyisoprenoid esterifying alcohols and
      produces more heterogeneous BChl c homologs in chlorosomes. Substitution of
      phytol for stearyl alcohol of BChl c maintains similar morphology of the intact
      chlorosome and enhances energy transfer from the chlorosome to the membrane-bound
      photosynthetic apparatus. Different morphologies of the intact chlorosome versus
      in vitro BChl aggregates are suggested by small-angle neutron scattering.
      Additionally, phytol cultures and 44  degrees C cultures exhibit slow assembly of
      the chlorosome. These results suggest that the esterifying alcohol of BChl c
      contributes to long-range organization of BChls, and that interactions between
      BChls with other components are important to the assembly of the chlorosome.
      Possible mechanisms for how esterifying alcohols affect the biogenesis of the
      chlorosome are discussed. 

PMID- 24880611
TI  - IRAK1: oncotarget in MDS and AML.

PMID- 24880612
TI  - Influence of alkyl chain length on the mesomorphism of 5-S-alkyl-5
      thiopentonolactones and 5-S-alkyl-5-thiopentitols.
AB  - Mesomorphic properties of S-alkylthiopentonolactones (d-ribono, d-arabinono and d
      xylono) and corresponding alditol derivatives with the general formula Su-SR
      (R=CnH2n+1; n=5-12) are studied. It was shown that the thermotropic and lyotropic
      phase transition temperatures are influenced by the following structural
      parameters: alkyl chain length, cyclic or acyclic Su structure and alditol
      conformation. Besides, it seems that n parity affects thermotropic phase
      transition temperatures.

PMID- 24880614
TI  - Pathogenic Neisseria meningitidis utilizes CD147 for vascular colonization.
AB  - Neisseria meningitidis is a cause of meningitis epidemics worldwide and of
      rapidly progressing fatal septic shock. A crucial step in the pathogenesis of
      invasive meningococcal infections is the adhesion of bloodborne meningococci to
      both peripheral and brain endothelia, leading to major vascular dysfunction.
      Initial adhesion of pathogenic strains to endothelial cells relies on
      meningococcal type IV pili, but the endothelial receptor for bacterial adhesion
      remains unknown. Here, we report that the immunoglobulin superfamily member CD147
      (also called extracellular matrix metalloproteinase inducer (EMMPRIN) or Basigin)
      is a critical host receptor for the meningococcal pilus components PilE and PilV.
      Interfering with this interaction potently inhibited the primary attachment of
      meningococci to human endothelial cells in vitro and prevented colonization of
      vessels in human brain tissue explants ex vivo and in humanized mice in vivo.
      These findings establish the molecular events by which meningococci target human
      endothelia, and they open new perspectives for treatment and prevention of
      meningococcus-induced vascular dysfunctions. 

PMID- 24880615
TI  - On-demand intracellular amplification of chemoradiation with cancer-specific
      plasmonic nanobubbles.
AB  - Chemoradiation-resistant cancers limit treatment efficacy and safety. We show
      here the cancer cell-specific, on-demand intracellular amplification of
      chemotherapy and chemoradiation therapy via gold nanoparticle- and laser pulse
      induced mechanical intracellular impact. Cancer aggressiveness promotes the
      clustering of drug nanocarriers and gold nanoparticles in cancer cells. This
      cluster, upon exposure to a laser pulse, generates a plasmonic nanobubble, the
      mechanical explosion that destroys the host cancer cell or ejects the drug into
      its cytoplasm by disrupting the liposome and endosome. The same cluster locally
      amplifies external X-rays. Intracellular synergy of the mechanical impact of
      plasmonic nanobubble, ejected drug and amplified X-rays improves the efficacy of
      standard chemoradiation in resistant and aggressive head and neck cancer by 100
      fold in vitro and 17-fold in vivo, reduces the effective entry doses of drugs and
      X-rays to 2-6% of their clinical doses and efficiently spares normal cells. The
      developed quadrapeutics technology combines four clinically validated components
      and transforms a standard macrotherapy into an intracellular on-demand
      theranostic microtreatment with radically amplified therapeutic efficacy and
      specificity. 

PMID- 24880613
TI  - Defining the toxicology of aging.
AB  - Mammalian aging is complex and incompletely understood. Although significant
      effort has been spent addressing the genetics or, more recently, the pharmacology
      of aging, the toxicology of aging has been relatively understudied. Just as an
      understanding of 'carcinogens' has proven crucial to modern cancer biology, an
      understanding of environmental toxicants that accelerate aging ('gerontogens')
      will inform gerontology. In this review, we discuss the evidence for the
      existence of mammalian gerontogens, as well as describe the biomarkers needed to
      measure the age-promoting activity of a given toxicant. We focus on the effects
      of putative gerontogens on the in vivo accumulation of senescent cells, a
      characteristic feature of aging that has a causal role in some age-associated
      phenotypes. 

PMID- 24880616
TI  - Increased gene copy number of VAMP7 disrupts human male urogenital development
      through altered estrogen action.
AB  - Despite the fact that genitourinary defects are among the most common birth
      defects in newborns, little is known about their etiology. Here we analyzed
      children born with congenital genitourinary tract masculinization disorders by
      array-comparative genomic hybridization, which revealed in 1.35% of cases the
      presence of de novo copy number gains at Xq28 encompassing the VAMP7 gene, which
      encodes a vesicle-trafficking protein that is part of the SNARE complex.
      Transgenic mice carrying a bacterial artificial chromosome encoding human VAMP7
      mimicked the defective urogenital traits observed in boys with masculinization
      disorders such as cryptorchidism, urethral defects and hypospadias. Transgenic
      mice also exhibited reduced penile length, focal spermatogenic anomalies,
      diminished sperm motility and subfertility. VAMP7 colocalized with estrogen
      receptor alpha (ESR1) in the presence of its cognate ligand, 17beta-estradiol.
      Elevated levels of VAMP7 markedly intensified ESR1-potentiated transcriptional
      activity by increasing ESR1 protein cellular content upon ligand stimulation and
      upregulated the expression of estrogen-responsive genes including ATF3, CYR61 and
      CTGF, all of which have been implicated in human hypospadias. Hence, increased
      gene dosage of VAMP7, and thus higher expression levels of its protein product,
      enhances estrogen receptor action in male genitourinary tissues, affects the
      virilization of the reproductive tract and results in genitourinary birth defects
      in humans. 

PMID- 24880618
TI  - Inhibitory effects of ZnO nanoparticles on aerobic wastewater biofilms from
      oxygen concentration profiles determined by microelectrodes.
AB  - The presence of ZnO NPs in waste streams can negatively affect the efficiency of
      biological nutrient removal from wastewater. However, details of the toxic
      effects of ZnO NPs on microbial activities of wastewater biofilms have not yet
      been reported. In this study, the temporal and spatial inhibitory effects of ZnO
      NPs on the O2 respiration activities of aerobic wastewater biofilms were
      investigated using an O2 microelectrode. The resulting time-course microelectrode
      measurements demonstrated that ZnO NPs inhibited O2 respiration within 2h. The
      spatial distributions of net specific O2 respiration were determined in biofilms
      with and without treatment of 5 or 50mg/L ZnO NPs. The results showed that 50mg/L
      of nano-ZnO inhibited the microbial activities only in the outer layer (~200MUm)
      of the biofilms, and bacteria present in the deeper parts of the biofilms became
      even more active. Scanning electron microscopy (SEM) analysis showed that the ZnO
      NPs were adsorbed onto the biofilm, but these NPs had no adverse effects on the
      cell membrane integrity of the biofilms. It was found that the inhibition of O2
      respiration induced by higher concentrations of ZnO NPs (50mg/L) was mainly due
      to the release of zinc ions by dissolution of the ZnO NPs. 

PMID- 24880617
TI  - Tumorigenicity and genetic profiling of circulating tumor cells in small-cell
      lung cancer.
AB  - Small-cell lung cancer (SCLC), an aggressive neuroendocrine tumor with early
      dissemination and dismal prognosis, accounts for 15-20% of lung cancer cases and
      ~200,000 deaths each year. Most cases are inoperable, and biopsies to investigate
      SCLC biology are rarely obtainable. Circulating tumor cells (CTCs), which are
      prevalent in SCLC, present a readily accessible 'liquid biopsy'. Here we show
      that CTCs from patients with either chemosensitive or chemorefractory SCLC are
      tumorigenic in immune-compromised mice, and the resultant CTC-derived explants
      (CDXs) mirror the donor patient's response to platinum and etoposide
      chemotherapy. Genomic analysis of isolated CTCs revealed considerable similarity
      to the corresponding CDX. Most marked differences were observed between CDXs from
      patients with different clinical outcomes. These data demonstrate that CTC
      molecular analysis via serial blood sampling could facilitate delivery of
      personalized medicine for SCLC. CDXs are readily passaged, and these unique mouse
      models provide tractable systems for therapy testing and understanding drug
      resistance mechanisms. 

PMID- 24880619
TI  - Intraorbital injection of rituximab versus high dose of systemic glucocorticoids
      in the treatment of thyroid-associated orbitopathy.
AB  - The aim of the study was to compare, in a randomized prospective study, the
      efficacy and safety of intraorbital administration of low doses of RTX versus
      intravenous glucocorticoids (GCs) to treat patients affected by moderately severe
      thyroid-associated active orbitopathy. Twenty patients with active, moderately
      severe TAO, whose mean age was 56.7 years+/-10.2 SD participated in the study.
      Patients were randomly selected and treated with intraorbital injections of RTX
      or with i.v. GCs. Disease activity and severity were assessed by the Clinical
      Activity Score (CAS) and the NOSPECS. Computed tomography or magnetic resonance
      scans were performed in all patients. In the RTX group, full blood cell count and
      flow cytometric analysis on peripheral blood lymphocytes were done. The patients
      were followed for 20 months. In both groups, CAS and NOSPECS indexes were
      significantly reduced (p<0.005). In particular, CAS reduction was evident since
      the first follow-up with both treatments. Proptosis decreased significantly only
      in group B and diplopia showed no significant changes during follow-up times in
      both groups. Neither of the treatments affected the peripheral TRab. In group A,
      5 weeks after the first injection, the CD20+ peripheral lymphocytes value was
      nearly zero. One patient treated with rituximab progressed to severe TAO (optic
      neuropathy) following the second injection so the treatment was discontinued. The
      data confirm the therapeutic efficacy of RTX in active TAO, even in low doses and
      locally administered. The efficacy on the inflammatory component of the disease
      is comparable to that of steroids and seems to be related with the reduction of
      peripheral CD20+ lymphocytes. Caution should be given to an accurate patient
      selection.

PMID- 24880620
TI  - Examination of the fasting and 2-h plasma glucose in the light of impairment in
      beta-cell function: what does the epidemiological data tell us?
AB  - We re-assess the fasting plasma glucose (FPG) and 2-h post-load glucose (2HPG) in
      the diagnosis of both prediabetes and type 2 diabetes mellitus by developing a
      gold standard based on beta-cell function. The gold standard was developed in a
      cohort of 2,152 adult subjects without severe renal or liver dysfunction that
      also had a 2-h oral glucose tolerance test (OGTT) during the Third National
      Health and Nutrition Examination Survey. Beta-cell function was computed based on
      a composite of insulin secretion (determined based on the insulin and glucose
      responses to the OGTT) and the homeostasis model insulin resistance index. The X
      tile program was used to generate the most appropriate categories of minor,
      moderate and severe impairment of beta-cell function based on the best
      discrimination of ln(insulin secretion). Subjects with a moderate or severe
      impairment in beta-cell function were used to define prediabetes and diabetes,
      respectively, and was the standard against which the FPG and 2HPG were evaluated.
      It is shown that the current definitions of diabetes by the FPG and 2HPG mirror
      those derived using impairment of beta-cell function as the gold standard. It is
      also shown that lowering the cutoff for the FPG does little to improve its use in
      the screening for prediabetes. A major finding is that the current 2HPG cutoff is
      inadequate and thus in need of revision to >6.7 mmol/L (>120 mg/dL) from 7.8
      mmol/L (140 mg/dL) for the lower cutoff. The use of a model of beta-cell function
      and impairment of insulin secretion has thus put the utility of the FPG and 2HPG
      into perspective: We recommend that performing an OGTT be considered pivotal for
      accurate identification of subjects with impaired beta-cell function (and thus
      prediabetes) and a revision of the OGTT lower cutoff be considered based on the
      results of this study.

PMID- 24880621
TI  - Ultrasound B-flow imaging in the evaluation of thermal ablation of thyroid
      nodules.
AB  - The aim of percutaneous thermal ablation is to reduce the volume of benign
      thyroid nodules. B-flow imaging, a non-Doppler technology for blood flow imaging,
      provides a real-time visualization of vascularity, and gives accurate information
      on the vessel lumen in high spatial and temporal resolution. Little is known
      about the possible application of this new technique on thyroid nodules after
      thermal treatments. Color power Doppler and contrast-enhanced ultrasound are the
      methods currently used in this context, but they present some limitations.
      Conversely, during the thermal procedures, B-flow imaging--suppressing unwanted
      signals (e.g., noise and tissue) and boosting weak signals (e.g., blood echoes)-
      permits an accurate spatial analysis of the intranodular flow. B-flow imaging may
      clearly show a complete ablation during the treatment. Moreover, it can also be
      useful during the follow-up in highlighting the possible intranodular flow
      regrowth. In conclusion, B-flow imaging--overcoming the limitations of color
      power Doppler and contrast-enhanced ultrasound-is useful to evaluate, in real
      time, the necrotic area of thyroid nodules during and after thermal ablative
      procedures.

PMID- 24880622
TI  - A polymorphism near MC4R gene (rs17782313) is associated with serum triglyceride
      levels in the general Japanese population: the J-MICC Study.
AB  - Previously reported associations of a common polymorphism near melanocortin-4
      receptor (MC4R) gene (rs17782313) with BMI/obesity were inconsistent, especially
      in East Asia, and the associations of the polymorphism with serum lipid levels
      have not been fully elucidated. This study evaluated the association between
      rs17782313 and obesity-related traits and serum lipid levels in the general
      Japanese population. A total of 2,035 subjects (aged 35-69 years, 1,024 males and
      1,011 females) enrolled in the Japan Multi-Institutional Collaborative Cohort (J
      MICC) Study. We examined the associations between near MC4R polymorphism
      (rs17782313) and obesity-related traits [height, weight, body mass index (BMI),
      weight change from 20 years old], serum lipid levels (triglycerides, total and
      HDL-cholesterol), and intake of nutrients (total energy and macronutrients).
      Polymorphism of rs17782313 (minor C allele) was positively associated with serum
      triglyceride levels (P for trend = 0.020) adjusted for age and sex. Analysis
      using a general linear model revealed that the number of minor C alleles was
      positively associated with serum triglyceride levels after adjustment for age,
      sex, and potential confounders (P for trend = 0.004). Statistical significance
      did not change after further adjustment for total energy intake and BMI. There
      was no significant association between rs17782313 and obesity-related traits
      including BMI. Interactions between rs17782313 and sex, BMI, or total energy
      intake for triglyceride levels were not significant. To our knowledge, this study
      demonstrated for the first time that rs17782313 was associated with serum
      triglyceride levels in Asian population. Further studies are needed to confirm
      this result.

PMID- 24880624
TI  - Improving early detection of exotic or emergent oyster diseases in France:
      identifying factors associated with shellfish farmer reporting behaviour of
      oyster mortality.
AB  - Farmers' vigilance is essential for the detection of epidemics, including
      potential emerging diseases, in marine shellfish. A field study was conducted to
      investigate oyster farmers' reporting practices and behaviour, and to identify
      factors influencing the reporting process of oyster mortality, with the ultimate
      aim of improving early detection of unexplained oyster mortality outbreaks. A
      retrospective case-control study of oyster farmers from Charente-Maritime
      (France) was designed, based on interviews with 27 non-reporting and 89 reporting
      farmers, further split into 40 formerly-reporting and 49 currently-reporting
      farmers. Information about farmer and farm characteristics, farming practices,
      farm health history and related financial compensation on the farm, knowledge of
      the mortality reporting system and reporting behaviour was collected. Sampling
      design was considered in the calculations and farmers' reporting behaviour was
      modelled using an ordinal logistic regression (continuation-ratio model).
      Notification procedures were fairly well known among farmers and the reporting
      system was well accepted overall. Nevertheless, a lack of awareness of the aims
      of the reporting system was revealed, which contributed to late reporting.
      Factors identified as driving a farmer's decision to report oyster mortality
      concerned their lack of awareness of mortality reporting (production type, farm
      size, location of the production cycle, accessibility of the leasing grounds) and
      willingness to report (possibility and extent of financial compensation, a
      feeling of not being involved, whether it was first year of reporting). Overall
      classification performance of the model built in this study was 64%. In
      particular, financial compensation for oyster production losses appeared to be a
      clear incentive for reporting, but was countered by a habituation effect combined
      with a lack of awareness of the aims of the reporting system: oyster farmers
      looking for benefits for themselves in reporting, rather than early detection of
      a disease outbreak. Both economic compensation and the farmers' non-economic
      values and perceptions should be considered to improve oyster farmers' reporting
      compliance and sustainability of the reporting system. Education and
      participatory approaches could help to change these attitudes and thus improve
      oyster farmers' compliance with reporting duties, resulting in improved early
      detection of epidemics and emerging or exotic oyster diseases. 

PMID- 24880623
TI  - Schmallenberg virus epidemic: impact on milk production, reproductive performance
      and mortality in dairy cattle in the Netherlands and Kleve district, Germany.
AB  - Schmallenberg virus (SBV), a novel orthobunyavirus that rapidly spread throughout
      north-western Europe in 2011, caused congenital malformations in lambs and goat
      kids (Van den Brom et al., 2012) and newborn calves (Hoffmann et al., 2012). The
      impact of the SBV epidemic seemed limited however, in terms of the number of
      affected herds with malformed offspring (European Food Safety Authority, 2012b).
      Nevertheless, little is known with regard to the overall within-herd impact of
      SBV infection. The objective of the current study was to quantify the impact of
      the 2011 SBV epidemic on the productivity of dairy cattle in the Netherlands and
      the district of Kleve, Germany. For the Netherlands, several multilevel
      multivariable statistical models were applied on eight productivity parameters
      regarding milk production, reproductive performance and mortality. All four
      fertility parameters analysed were slightly but significantly reduced between
      August 1st and November 1st 2011 compared to the reference period in 2009-2010.
      Between August 15th and September 19th 2011, the average loss in milk production
      per cow was -0.26kg (95% CI: -0.30; -0.22) per day in dairy herds, compared to
      the reference period (p<0.001). The total loss per cow in a subgroup of dairy
      herds that notified malformations in newborn calves during the mandatory
      notification period in the Netherlands was -0.43kg (95% CI: -0.59; -0.28) per day
      (p<0.001). For Germany, a study was carried out in the district of Kleve,
      situated in the state of North Rhine-Westphalia near the Dutch border. Data on
      milk yield, two fertility parameters and the number of rendered calves in this
      specific region were analysed. There was a small but significant increase in the
      number of secondary and third inseminations between August 1st and November 1st
      2011, indicating reduced fertility. No significant change in calf mortality was
      observed in the assumed SBV period. Milk production at district level did not
      seem to be affected by SBV in August and September 2011. SBV had no or limited
      impact on mortality rates, which was as expected given the relatively mild
      expression of SBV in adult cows and the low incidence of notified malformations
      in newborn calves. Our results indicate that SBV had a limited impact on
      productivity of dairy cattle. However, the total economic impact of SBV on the
      ruminant industry not only consists of productivity caused losses; it is expected
      that international trade restrictions formed a larger part of the total economic
      impact.

PMID- 24880625
TI  - Inadequate passive immune transfer in puppies: definition, risk factors and
      prevention in a large multi-breed kennel.
AB  - The prevalence of neonatal mortality is high in the canine species and far from
      well-studied. In most domestic neonates, an appropriate colostrum intake is a key
      element of the control of neonatal mortality. The aim of this study was to
      evaluate the impact of passive immune transfer on puppy mortality, assessed
      through serum immunoglobulin G (IgG) concentration at 2 days of age. Factors
      impacting passive immune transfer and the value of an oral immunoglobulin
      supplementation to prevent it were also analyzed. A total of 149 puppies from 34
      litters (12 breeds) within one breeding kennel were included. Blood samples were
      collected at 2 days of age and colostrum was collected from their dams 1 day
      after whelping to assay IgG concentration. Puppies were weighed at birth and at 2
      days of age for calculation of growth rate. Mortality was recorded until 3 weeks
      of age. Seventy randomly assigned puppies were orally supplemented with hyper
      immunized adult plasma twice within the first 8h of life. IgG concentration at 2
      days of age was significantly correlated with weight gain during the first 2 days
      of life. The multivariable model with litter as a random effect demonstrated that
      neonatal mortality was not influenced by breed size, sex, supplementation, litter
      size, nor colostrum IgG concentration, but by puppy IgG concentration at 2 days
      of age. According to the ROC curve, the minimal IgG concentration at and below
      which puppies were at higher risk of death was determined at 230 mg/dl. Puppy IgG
      concentration was significantly associated with growth rate, but not with breed
      size, sex, supplementation, litter size or colostrum IgG concentration in a
      multivariable model with litter as a random effect. This study demonstrates that
      neonatal mortality in puppies is related to the quality of passive immune
      transfer. The oral supplementation with hyper-immunized canine plasma neither
      decreased risk of mortality, nor improved serum IgG concentration at 2 days of
      age in puppies. Attention must thus be paid to early colostrum intake to control
      the neonatal mortality in puppies.

PMID- 24880626
TI  - The development of poultry farms risk assessment tool for avian influenza in Imo
      State, Nigeria.
AB  - This study validated the content of a questionnaire that will be used for risk
      stratification in poultry farms in Imo State, Nigeria. The questionnaire was
      developed from avian influenza risk domains peculiar to poultry farms in Nigeria.
      The questionnaire was verified and modified by a group of five experts with
      research interest in Nigeria's poultry industry and avian influenza prevention.
      The questionnaire was distributed to 30 poultry farms selected from Imo State,
      Nigeria. The same poultry farms were visited one week after they completed the
      questionnaires for on-site observation. Agreement between survey and observation
      results was analyzed using the kappa statistic and rated as poor, fair, moderate,
      substantial, or nearly perfect; internal consistency of the survey was also
      computed. The mean kappa statistic for agreement between the survey and
      observations (validation) ranged from 0.06 to 1, poor to nearly perfect
      agreement. Eight questions showed poor agreement, four had a fair agreement, two
      items had moderate agreement, nineteen survey questions had substantial agreement
      and ten questions had nearly perfect agreement. Out of the 43 items in the
      questionnaire, 32 items were considered validated with coefficient alpha >0.70. 

PMID- 24880627
TI  - Characterization of a F280N variant of L-arabinose isomerase from Geobacillus
      thermodenitrificans identified as a D-galactose isomerase.
AB  - The double-site variant (C450S-N475K) L-arabinose isomerase (L-AI) from
      Geobacillus thermodenitrificans catalyzes the isomerization of D-galactose to D
      tagatose, a functional sweetener. Using a substrate-docking homology model, the
      residues near to D-galactose O6 were identified as Met186, Phe280, and Ile371.
      Several variants obtained by site-directed mutagenesis of these three residues
      were analyzed, and a triple-site (F280N) variant enzyme exhibited the highest
      activity for D-galactose isomerization. The k cat/K m of the triple-site variant
      enzyme for D-galactose was 2.1-fold higher than for L-arabinose, whereas the k
      cat/K m of the double-site variant enzyme for L-arabinose was 43.9-fold higher
      than for D-galactose. These results suggest that the triple-site variant enzyme
      is a D-galactose isomerase. The conversion rate of D-galactose to D-tagatose by
      the triple-site variant enzyme was approximately 3-fold higher than that of the
      double-site variant enzyme for 30 min. However, the conversion yields of L
      arabinose to L-ribulose by the triple-site and double-site variant enzymes were
      10.6 and 16.0 % after 20 min, respectively. The triple-site variant enzyme
      exhibited increased specific activity, turnover number, catalytic efficiency, and
      conversion rate for D-galactose isomerization compared to the double-site variant
      enzyme. Therefore, the amino acid at position 280 determines the substrate
      specificity for D-galactose and L-arabinose, and the triple-site variant enzyme
      has the potential to produce D-tagatose on an industrial scale.

PMID- 24880628
TI  - Cultivation of nitrite-dependent anaerobic methane-oxidizing bacteria: impact of
      reactor configuration.
AB  - Nitrite-dependent anaerobic methane oxidation (n-damo) is mediated by bacteria
      that anaerobically oxidize methane coupled with nitrite reduction and is a
      potential bioprocess for wastewater treatment. In this work, the effect of
      reactor configuration on n-damo bacterial cultivation was investigated. A
      magnetically stirred gas lift reactor (MSGLR), a sequencing batch reactor (SBR),
      and a continuously stirred tank reactor (CSTR) were selected to cultivate the
      bacteria. Microbial community was monitored by using quantitative PCR, 16S rRNA
      gene sequencing, pmoA gene sequencing, and fluorescence in situ hybridization
      (FISH). The effects of substrate inhibition, methane mass transfer, and biomass
      washout in the three reactors were focused on. The results indicated that the
      MSGLR had the best performance among the three reactor systems, with the highest
      total and specific n-damo activities. Its maximum volumetric nitrogen removal
      rate was up to 76.9 mg N L(-1) day(-1), which was higher than previously reported
      values (5.1-37.8 mg N L(-1) d(-1)). 

PMID- 24880629
TI  - Salinity-dominated change in community structure and ecological function of
      Archaea from the lower Pearl River to coastal South China Sea.
AB  - Archaea have multiple roles in global biogeochemical cycles. However, we still
      have limited knowledge about how environmental factors affect the diversity and
      function of different archaeal lineages. The goal of this study was to examine
      the change in the abundance and community structure of Archaea in the sediments
      collected from the lower Pearl River (mainly North River tributary), its estuary,
      and coastal South China Sea (SCS) in order to evaluate how archaeal ecological
      function might change along the salinity gradient. Pyrosequencing of the 16S rDNA
      gene of Archaea was performed on sediment samples from Feilaixia Dam on the North
      River tributary to Wanshan islands, which have a salinity range of 0.1 to
      31.20/00. Consistent with the salt tolerance of cultivated representatives,
      methanogens in the genera Methanoregula, Methanosaeta, and Methanosarcina and
      Nitrososphaera within Thaumarchaeota of the ammonia-oxidizing Archaea (AOA) were
      abundant in freshwater sediments of the North River tributary, whereas the marine
      associated genera Methanococcoides and Nitrosopumilus were the most abundant
      methanogens and AOA, respectively, in the estuary and coastal SCS. However, the
      percentages of total methanogens decreased and Thaumarchaeota increased with
      salinity, respectively. The phylum Crenarchaeota was largely represented by class
      level lineages with no cultivated representatives, which collectively were more
      abundant in the estuary and coastal SCS in comparison to freshwater sites. This
      study indicates that salinity is the dominating factor affecting archaeal
      community structure and ecological function from the North River tributary of the
      Pearl River, its estuary, and coastal SCS, which is consistent with salinity
      control on microbial diversity in other regions of the world.

PMID- 24880630
TI  - Genomic and protein expression analysis reveals flap endonuclease 1 (FEN1) as a
      key biomarker in breast and ovarian cancer.
AB  - FEN1 has key roles in Okazaki fragment maturation during replication, long patch
      base excision repair, rescue of stalled replication forks, maintenance of
      telomere stability and apoptosis. FEN1 may be dysregulated in breast and ovarian
      cancers and have clinicopathological significance in patients. We comprehensively
      investigated FEN1 mRNA expression in multiple cohorts of breast cancer [training
      set (128), test set (249), external validation (1952)]. FEN1 protein expression
      was evaluated in 568 oestrogen receptor (ER) negative breast cancers, 894 ER
      positive breast cancers and 156 ovarian epithelial cancers. FEN1 mRNA
      overexpression was highly significantly associated with high grade (p = 4.89 *
      10(-57)), high mitotic index (p = 5.25 * 10(-28)), pleomorphism (p = 6.31 * 10(
      19)), ER negative (p = 9.02 * 10(-35)), PR negative (p = 9.24 * 10(-24)), triple
      negative phenotype (p = 6.67 * 10(-21)), PAM50.Her2 (p = 5.19 * 10(-13)), PAM50.
      Basal (p = 2.7 * 10(-41)), PAM50.LumB (p = 1.56 * 10(-26)), integrative molecular
      cluster 1 (intClust.1) (p = 7.47 * 10(-12)), intClust.5 (p = 4.05 * 10(-12)) and
      intClust. 10 (p = 7.59 * 10(-38)) breast cancers. FEN1 mRNA overexpression is
      associated with poor breast cancer specific survival in univariate (p = 4.4 * 10(
      16)) and multivariate analysis (p = 9.19 * 10(-7)). At the protein level, in ER
      positive tumours, FEN1 overexpression remains significantly linked to high grade,
      high mitotic index and pleomorphism (ps < 0.01). In ER negative tumours, high
      FEN1 is significantly associated with pleomorphism, tumour type, lymphovascular
      invasion, triple negative phenotype, EGFR and HER2 expression (ps < 0.05). In ER
      positive as well as in ER negative tumours, FEN1 protein overexpression is
      associated with poor survival in univariate and multivariate analysis (ps <
      0.01). In ovarian epithelial cancers, similarly, FEN1 overexpression is
      associated with high grade, high stage and poor survival (ps < 0.05). We conclude
      that FEN1 is a promising biomarker in breast and ovarian epithelial cancer.

PMID- 24880631
TI  - Physical activity monitoring in patients with peripheral arterial disease:
      validation of an activity monitor.
AB  - OBJECTIVES: The daily life physical activity (PA) of patients with peripheral
      arterial disease (PAD) may be severely hampered by intermittent claudication
      (IC). From a therapeutic, as well as research, point of view, it may be more
      relevant to determine improvement in PA as an outcome measure in IC. The aim of
      this study was to validate daily activities using a novel type of tri-axial
      accelerometer (Dynaport MoveMonitor) in patients with IC. METHODS: Patients with
      IC were studied during a hospital visit. Standard activities (locomotion, lying,
      sitting, standing, shuffling, number of steps and "not worn" detection) were
      video recorded and compared with activities scored by the MoveMonitor. Inter
      rater reliability (expressed in intraclass correlation coefficients [ICC]),
      sensitivity, specificity, and positive predictive values (PPV) were calculated
      for each activity. RESULTS: Twenty-eight hours of video observation were analysed
      (n = 21). Our video annotation method (the gold standard method) appeared to be
      accurate for most postures (ICC > 0.97), except for shuffling (ICC = 0.38). The
      MoveMonitor showed a high sensitivity (>86%), specificity (>91%), and PPV (>88%)
      for locomotion, lying, sitting, and "not worn" detection. Moderate accuracy was
      found for standing (46%), while shuffling appeared to be undetectable (18%). A
      strong correlation was found between video recordings and the MoveMonitor with
      regard to the calculation of the "number of steps" (ICC = 0.90). CONCLUSIONS: The
      MoveMonitor provides accurate information on a diverse set of postures, daily
      activities, and number of steps in IC patients. However, the detection of low
      amplitude movements, such as shuffling and "sitting to standing" transfers, is a
      matter of concern. This tool is useful in assessing the role of PA as a novel,
      clinically relevant outcome parameter in IC.

PMID- 24880632
TI  - Filaggrin-stratified transcriptomic analysis of pediatric skin identifies
      mechanistic pathways in patients with atopic dermatitis.
AB  - BACKGROUND: Atopic dermatitis (AD; eczema) is characterized by a widespread
      abnormality in cutaneous barrier function and propensity to inflammation.
      Filaggrin is a multifunctional protein and plays a key role in skin barrier
      formation. Loss-of-function mutations in the gene encoding filaggrin (FLG) are a
      highly significant risk factor for atopic disease, but the molecular mechanisms
      leading to dermatitis remain unclear. OBJECTIVE: We sought to interrogate tissue
      specific variations in the expressed genome in the skin of children with AD and
      to investigate underlying pathomechanisms in atopic skin. METHODS: We applied
      single-molecule direct RNA sequencing to analyze the whole transcriptome using
      minimal tissue samples. Uninvolved skin biopsy specimens from 26 pediatric
      patients with AD were compared with site-matched samples from 10 nonatopic
      teenage control subjects. Cases and control subjects were screened for FLG
      genotype to stratify the data set. RESULTS: Two thousand four hundred thirty
      differentially expressed genes (false discovery rate, P < .05) were identified,
      of which 211 were significantly upregulated and 490 downregulated by greater than
      2-fold. Gene ontology terms for "extracellular space" and "defense response" were
      enriched, whereas "lipid metabolic processes" were downregulated. The subset of
      FLG wild-type cases showed dysregulation of genes involved with lipid metabolism,
      whereas filaggrin haploinsufficiency affected global gene expression and was
      characterized by a type 1 interferon-mediated stress response. CONCLUSION: These
      analyses demonstrate the importance of extracellular space and lipid metabolism
      in atopic skin pathology independent of FLG genotype, whereas an aberrant defense
      response is seen in subjects with FLG mutations. Genotype stratification of the
      large data set has facilitated functional interpretation and might guide future
      therapy development.

PMID- 24880634
TI  - Clinical features and resolution of food protein-induced enterocolitis syndrome:
      10-year experience.
AB  - BACKGROUND: Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE
      mediated food allergy. FPIES diagnosis is frequently delayed because of the
      absence of classic allergic symptoms and lack of biomarkers. OBJECTIVE: We sought
      to characterize the clinical features and resolution of FPIES in patients
      evaluated in our practice. METHODS: Subjects 6 months to 45 years of age with
      FPIES were prospectively recruited for oral food challenges (OFCs). Medical
      records were searched to identify the subjects who did not participate in OFCs.
      RESULTS: Among 160 subjects, 54% were male; median age at diagnosis was 15
      months. We performed 180 OFCs to 15 foods in 82 subjects; 30% of the study
      population had FPIES confirmed based on OFC results. The most common foods were
      cow's milk (44%), soy (41%), rice (22.5%), and oat (16%). The majority (65%)
      reacted to 1 food, 26% reacted to 2 foods, and 9% reacted to 3 or more foods. The
      majority were atopic, and 39% had IgE sensitization to another food. Thirty-nine
      (24%) subjects had positive specific IgE levels to the food inducing FPIES. Among
      children with specific IgE to cow's milk, 41% changed from a milk FPIES to an IgE
      mediated phenotype over time. The median age when tolerance was established was
      4.7 years for rice, 4 years for oat, and 6.7 years for soy. Median age when milk
      tolerance was established for subjects with undetectable milk-specific IgE levels
      was 5.1 years, whereas none of the subjects with detectable milk-specific IgE
      became tolerant to milk during the study (P = .003). CONCLUSION: FPIES typically
      resolves by age 5 years. Milk FPIES, especially with detectable food-specific
      IgE, can have a protracted course and eventually transition to acute reactions.

PMID- 24880633
TI  - Do lipids influence the allergic sensitization process?
AB  - Allergic sensitization is a multifactorial process that is not only influenced by
      the allergen and its biological function per se but also by other small molecular
      compounds, such as lipids, that are directly bound as ligands by the allergen or
      are present in the allergen source. Several members of major allergen families
      bind lipid ligands through hydrophobic cavities or electrostatic or hydrophobic
      interactions. These allergens include certain seed storage proteins, Bet v 1-like
      and nonspecific lipid transfer proteins from pollens and fruits, certain inhalant
      allergens from house dust mites and cockroaches, and lipocalins. Lipids from the
      pollen coat and furry animals and the so-called pollen-associated lipid mediators
      are codelivered with the allergens and can modulate the immune responses of
      predisposed subjects by interacting with the innate immune system and invariant
      natural killer T cells. In addition, lipids originating from bacterial members of
      the pollen microbiome contribute to the outcome of the sensitization process.
      Dietary lipids act as adjuvants and might skew the immune response toward a TH2
      dominated phenotype. In addition, the association with lipids protects food
      allergens from gastrointestinal degradation and facilitates their uptake by
      intestinal cells. These findings will have a major influence on how allergic
      sensitization will be viewed and studied in the future.

PMID- 24880635
TI  - Diagnosing overdiagnosis: conceptual challenges and suggested solutions.

PMID- 24880636
TI  - Disentangling Multiple Sclerosis and depression: an adjusted depression screening
      score for patient-centered care.
AB  - Screening for depression can be challenging in Multiple Sclerosis (MS) patients
      due to the overlap of depressive symptoms with other symptoms, such as fatigue,
      cognitive impairment and functional impairment, for MS patients. The aim of this
      study was to understand these overlapping symptoms and subsequently develop an
      adjusted depression screening tool for better clinical assessment of depressive
      symptoms in MS patients. We evaluated 3,507 MS patients with a self-reported
      depression screening (PHQ-9) score using a multiple indicator multiple cause
      modeling approach. Our models showed significant differential item functioning
      effects denoting significant overlap of depressive symptoms with all MS symptoms
      under study and good model fit. The magnitude of the overlap was especially large
      for fatigue. Adjusted depression screening scales were formed based on factor
      scores and loadings that will allow clinicians to understand the depressive
      symptoms separate from other symptoms for MS patients for improved patient care. 

PMID- 24880637
TI  - Immobilization and phytotoxicity of chromium in contaminated soil remediated by
      CMC-stabilized nZVI.
AB  - The toxic effect of Cr(VI)-contaminated soil remediated by sodium carboxymethyl
      cellulose stabilized nanoscale zero-valent iron (CMC-stabilized nZVI) was
      assessed through in vitro toxicity and phytotoxicity tests. In vitro tests showed
      that 0.09 g L(-1) of Fe(0) nanoparticles (soil-to-solution ratio was 1 g:5 mL)
      significantly reduced the toxicity characteristic leaching procedure (TCLP)
      leachability and physiological based extraction test (PBET) bioaccessibility of
      Cr by 82% and 58%, respectively. Sequential extraction procedures (SEP) revealed
      that exchangeable (EX) Cr was completely converted to Fe-Mn oxides (OX) and
      organic matter (OM). Accordingly, phytotoxicity tests indicated that after 72-h
      remediation, Cr uptakes by edible rape and Chinese cabbage were suppressed by 61%
      and 36%, respectively. Moreover, no significant increase in Cr uptake was
      observed for either species after a 1-month static period for the amended soil.
      Regarding Fe absorption, germination and seedling growth, both plant species were
      significantly affected by CMC-nZVI-exposed soils. However, similar phytotoxicity
      tests conducted after 1 month showed an improvement in cultivation for both
      plants. Overall, this study demonstrated that CMC-nZVI could significantly
      enhance Cr immobilization, which reduced its leachability, bioavailability and
      bioaccumulation by plants. From a detoxification perspective, such remediation is
      technologically feasible and shows great potential in field applications.

PMID- 24880638
TI  - Historical aspects of Mozart's mental health and diagnostic insights of ADHD and
      personality disorders.

PMID- 24880639
TI  - Chronic valproate or levetiracetam treatment does not influence cytokine levels
      in humans.
AB  - PURPOSE: There is growing evidence that complex interactions between seizures and
      the immune system shape the course of epilepsy. However, systematic analyses of
      the effects of antiepileptic drugs (AED) on the immune system in humans are rare.
      We performed a prospective study on the influence of the widely used AED
      valproate and levetiracetam on interictal immunological parameters. METHODS: 36
      patients were prospectively included. 15 were started on valproate (5 female
      (33%), age 54+/-27 years, 12 (80%) on monotherapy), 21 on levetiracetam (10
      female (48%), age 45+/-19 years, 17 (81%) on monotherapy). Before treatment and
      after 3 months, we performed a differential blood count and analyzed the
      distribution of CD3(+)CD4(+)-, CD3(+)CD8(+)- and CD4(+)CD25(+)-leukocyte subsets
      using flow cytometry. In addition, we determined the concentrations of IL-1beta,
      IL-6, TNF-alpha and MCP-1 in the peripheral blood using ELISAs. RESULTS:
      Valproate intake resulted in a significant decrease of the total white blood
      count (6.96+/-1.23/nl vs. 6.13+/-1.57/nl, p=0.026) and of absolute count and
      percentage of neutrophils (4.60+/-1.05/nl vs. 3.69+/-1.30/nl, p=0.01; 65.4+/-7.9%
      vs. 59.5+/-11.5%, p=0.01, respectively). The percentage of CD3(+)CD4(+)
      lymphocytes dropped significantly (50.4+/-10.9% vs. 45.3+/-12.3%, p=0.002).
      Levetiracetam treatment resulted in a decrease of the percentage of CD4(+)CD25(+)
      lymphocytes (26.1+/-8.0% vs. 21.5+/-9.2%, p=0.01) but did not significantly alter
      absolute counts. Neither valproate nor levetiracetam were associated with
      significant changes in cytokines. CONCLUSION: Valproate intake results in
      profound changes of white blood cell count and subset distribution. Cytokine
      levels were not influenced by valproate or levetiracetam.

PMID- 24880640
TI  - Miscanthus: genetic diversity and genotype identification using ISSR and RAPD
      markers.
AB  - Due to the limited number of molecular studies focused on European gene pool
      investigation, it is necessary to perform plant material recognition. Eighteen
      accessions of three Miscanthus species, namely, M. * giganteus, M. sinensis, M.
      sacchariflorus were evaluated with the use of molecular marker systems such as:
      inter simple sequence repeats (ISSRs), random amplified polymorphic DNA (RAPD),
      and by estimation of ploidy level based on flow cytometry. As a result, only one
      ISSR primer (ISSR1) and three RAPD primers (RAPD1, RAPD2, RAPD4) were required to
      identify all genotypes. Moreover, the use of the above mentioned molecular
      markers enable the proper species recognition of the interspecific hybrid M. *
      giganteus "Floridulus," which has been previously mislabeled as M. floridulus.
      The highest genetic similarity coefficient (0.94) was observed between M. *
      giganteus clones, which indicates that the genetic diversity within this species
      was very low. Whereas M. sinensis genotypes represented a relatively wide
      diversity with similarity coefficient of 0.58. Cluster analysis using UPGMA
      grouped the 18 accessions in three clusters according to species affiliation
      including relabeled M. * giganteus "Floridulus," which proved to be closely
      related to M.  * giganteus. Similar groupings were evident in the PCoA analysis. 

PMID- 24880641
TI  - Risk should be objectively defined: comment on Pele and Sueur.
AB  - Pele and Sueur (2013) propose that optimal decisions depend on delay of
      reinforcement, accuracy (probability or magnitude of reinforcement), and risk.
      The problem with this model is delay and accuracy are easy to define, but
      according to Pele and Sueur the third, risk, depends on the animal's perceived or
      "interpreted" risk rather than actual (experienced) risk. Thus, choice of the
      smaller more immediate reward over the larger delayed reward (the delay
      discounting function) is viewed by the authors as optimal because delay is
      associated with increased risk (due to potential competition or predation). But
      perceived risk is assessed by the decision made (e.g., the slope of the
      discounting function), and since there is virtually no actual risk involved, by
      default if there is no independent means of measuring risk, according to Pele and
      Sueur, all choices can be viewed as optimal. Thus, optimality is an untestable
      concept. We suggest that risk be defined by the actual risk (given sufficient
      experience to judge it) and under conditions in which there is no actual risk (or
      risk is controlled), when animals choose an alternative that provides a lower
      rate of access to food, that one considers such choice to be suboptimal. 

PMID- 24880642
TI  - Social comparison mediates chimpanzees' responses to loss, not frustration.
AB  - Why do chimpanzees react when their partner gets a better deal than them? Do they
      note the inequity or do their responses reflect frustration in response to
      unattainable rewards? To tease apart inequity and contrast, we tested chimpanzees
      in a series of conditions that created loss through individual contrast, through
      inequity, or by both. Chimpanzees were tested in four social and two individual
      conditions in which they received food rewards in return for exchanging tokens
      with an experimenter. In conditions designed to create individual contrast, after
      completing an exchange, the chimpanzees were given a relatively less-preferred
      reward than the one they were previously shown. The chimpanzees' willingness to
      accept the less-preferred rewards was independent of previously offered foods in
      both the social and individual conditions. In conditions that created frustration
      through inequity, subjects were given a less-preferred reward than the one
      received by their partner, but not in relation to the reward they were previously
      offered. In a social context, females were more likely to refuse to participate
      when they received a less-preferred reward than their partner (disadvantageous
      inequity), than when they received a more-preferred reward (advantageous
      inequity). Specifically, the females' refusals were typified by refusals to
      exchange tokens rather than refusals to accept food rewards. Males showed no
      difference in their responses to inequity or individual contrast. These results
      support previous evidence that some chimpanzees' responses to inequity are
      mediated more strongly by what others receive than by frustration effects. 

PMID- 24880643
TI  - Decreased strongyle egg re-appearance period after treatment with ivermectin and
      moxidectin in horses in Belgium, Italy and The Netherlands.
AB  - The objective of the present study was to evaluate the efficacy of an oral
      treatment with ivermectin (IVM) or moxidectin (MOX) against gastro-intestinal
      strongyles in naturally infected horses by performing a faecal egg count
      reduction test (FECRT) and by monitoring the egg reappearance period (ERP) after
      treatment. Therefore, a field efficacy study with a randomised complete block
      design for each study site was conducted, with the individual animal as the
      experimental unit. At least 10 study sites in Italy, Belgium and The Netherlands
      were selected and animals were allocated to one of the two treatment groups based
      on the pre-treatment faecal egg counts (FEC). Animals were treated on Day 0 with
      an oral paste containing either IVM (at 0.2mg/kg bodyweight) or MOX (at 0.4 mg/kg
      bodyweight). After treatment, faecal samples were collected at least every
      fortnight during 56 days after treatment with IVM and during 84 days after MOX
      treatment. In total, 320 horses on 32 farms were examined. The FECRT on Day 14
      indicated a 100% efficacy in 59 of the 64 treatment groups and >92% efficacy in
      the remaining 5 groups. The ERP was decreased for at least one of the
      anthelmintics on 17 out of 32 study sites (15 sites or 47% for MOX and 17 sites
      or 53% for IVM) and on 9 sites (28%) the ERP was decreased for both
      anthelmintics. On some of these study sites the efficacy declined at the end of
      the expected ERP, often with good efficacy 2 weeks earlier. Nevertheless, on 1, 3
      and 5 study sites in Italy, Belgium and The Netherlands respectively, an efficacy
      below 90% for IVM and MOX was identified as soon as Day 42 or Day 56. In The
      Netherlands, the efficacy of IVM was below 90% from Day 28 or Day 35 after
      treatment on 1 site each. The present study reports a high efficacy of MOX and
      IVM in a FECRT 14 days after treatment, yet does indicate a shortened ERP for
      these treatments in more than half of the selected study sites.

PMID- 24880644
TI  - Effects of sub-zero storage temperatures on endoparasites in canine and equine
      feces.
AB  - Fecal samples from wild and domestic carnivores are routinely frozen for three
      days at -80 degrees C to kill eggs of Echinococcus spp., following
      recommendations from the World Health Organization (WHO) and World Organization
      for Animal Health (OIE). This is done to decrease the risk of zoonotic infection
      with these pathogenic cestodes. In addition, it is often necessary to freeze
      fecal samples collected for research prior to batch processing by a limited
      number of personnel, especially large numbers of samples or those collected in
      remote locations. The effect of freezing on the recovery of endoparasite eggs,
      cysts and oocysts from fecal samples is not well documented, even in hosts for
      which veterinary diagnostic submissions are relatively common. In this study,
      fecal samples from naturally infected dogs and horses were split into four
      treatment groups: fresh; -80 degrees C for 3 days; -20 degrees C for 30 days; and
      -80 degrees C for 3 days followed by -20 degrees C for an additional 30 days.
      Temperatures and times were chosen to simulate diagnostic and research protocols
      currently in place. Helminth eggs and sporocysts of Sarcocystis spp. were counted
      using a quantitative double centrifugation sucrose fecal flotation (modified
      Stoll egg count). Repeated measures ANOVA was used to detect differences in
      egg/sporocyst counts between the treatment groups for Sarcocystis spp.
      sporocysts, taeniid eggs (Taenia and/or Echinococcus spp.), ascarid eggs
      (Parascaris equorum, Toxocara canis, Toxascaris leonina), and strongylid type
      eggs (Uncinaria stenocephala, and equine strongylids, most likely cyathostomins).
      Counts for P. equorum and strongylid type eggs (both equine and canine) decreased
      significantly following freezing. Post-freezing, some samples that had been
      positive on fresh examination became negative for Parascaris and strongylid eggs.
      This study suggests that protocols requiring freezing artificially lowers
      recovery of eggs of Parascaris and strongylid nematodes in fecal surveys;
      however, recovery rates for eggs of other helminth species as well as sporocysts
      of Sarcocystis spp. were relatively robust compared to the freshly tested fecal
      samples. This is reassuring for large scale fecal surveys needed for fecal egg
      count reduction analyses following treatment, and for surveillance in wildlife
      and remote human and animal populations. 

PMID- 24880645
TI  - Declines in canine endoparasite prevalence associated with the introduction of
      commercial heartworm and flea preventatives from 1984 to 2007.
AB  - The apparent monthly prevalence of endoparasite infections was measured from
      20,991 dogs that had fecal examinations performed upon presentation to the
      Veterinary Hospital of the University of Pennsylvania between 1984 and 2007. In
      the period from 1984 to 1991, the mean monthly prevalence of endoparasites was
      5.32% for ascarids, 9.80% for hookworms, 9.64% for whipworms, 1.84% for tapeworms
      (Dipylidium caninum), 4.59% for Giardia species, and 3.04% for coccidia. Based on
      Student's t tests, the prevalence of ascarids (1.99%), hookworms (1.48%),
      whipworms (2.33%), and tapeworms (0.29%) were found to be significantly lower in
      the period from 2000 to 2007. Plots of the smoothed monthly averages revealed
      that the declines in prevalence occurred shortly after the introduction of modern
      heartworm and flea preventatives to the commercial market. In the latter study
      period, 79.8% of dogs were on monthly heartworm prevention and 74.0% were on
      monthly flea prevention. There were no significant differences in the prevalence
      of either Giardia species or coccidia species between study time periods.
      Overall, the findings suggest that heartworm and flea preventatives have had
      cascade effects on endoparasite prevalence in the population of well-cared-for
      dogs. 

PMID- 24880646
TI  - The detection of Cryptosporidium serpentis in snake fecal samples by real-time
      PCR.
AB  - Infection by Cryptosporidium serpentis occurs in reptiles, particularly in
      snakes. This disease is characterized by chronic infection with the presence of
      hypertrophic gastritis. The objectives of this study were to use real-time
      polymerase chain reaction (PCR) targeting the heat shock protein 70 (Hsp70) gene
      for the detection of C. serpentis in fecal samples from snakes and to determine
      the analytical and epidemiological specificity and sensitivity of this approach
      relative to the gold standard of nested PCR for the amplification of a fragment
      of the 18S subunit of the ribosomal RNA (18S rRNA) gene followed by the
      sequencing of amplified fragments (nPCR/S). Individual fecal samples were
      collected on a single occasion from 503 asymptomatic adult snakes housed in the
      serpentarium of the Butantan Institute in Sao Paulo, Brazil. The nested PCR
      revealed that 60 samples (11.98%) were positive for Cryptosporidium sp. The
      sequencing of amplified fragments, which was possible for 38 samples, resulted in
      the identification of Cryptosporidium tyzzeri (7), Cryptosporidium muris (4),
      Cryptosporidium varanii (12) and C. serpentis (15) in fecal samples from several
      snake species. The real-time PCR approach indicated that 17 samples (3.37%) were
      positive for C. serpentis, whereas the nPCR/S indicated that 15 samples (2.98%)
      were positive for C. serpentis. The epidemiological sensitivity and specificity
      of real-time PCR were 93.8% and 99.5%, respectively. Thus, we conclude that real
      time PCR targeting the Hsp70 gene is a sensitive and specific method for the
      detection of C. serpentis in snake fecal samples. 

PMID- 24880647
TI  - Coprophagy in dogs interferes in the diagnosis of parasitic infections by faecal
      examination.
AB  - Many dogs display coprophagic behaviour. Helminth eggs can passively pass the
      dog's digestive tract and this may result in a false positive diagnosis of
      infection with gastrointestinal helminth parasites. For a period of one year,
      faecal samples of dogs were examined monthly using the Centrifugal Sedimentation
      Flotation (CSF) technique with a sugar flotation solution (s.g. 1.27-1.30
      g/cm(3)). If a sample tested positive for canine helminth eggs, the owner was
      asked to submit another sample after preventing the dog from eating faeces for 3
      days. If the second sample again tested positive for the same type of helminth
      egg, the dog was considered to have a patent infection. If the second sample
      tested negative, the first sample was considered a false positive due to
      coprophagy. The focus of this study was on dogs shedding Toxocara eggs. At the
      first examination, 246 samples (out of 308 samples testing positive for canine
      specific helminth eggs) tested positive for Toxocara spp. Of these, 120 (49%)
      tested negative at the second examination. Coprophagic behaviour was recognized
      by 261 of the 564 owners that answered the accompanying questionnaire. This
      concerned 391 dogs. Coproscopical examination also provided proof of coprophagy
      (e.g. oocysts of Eimeria spp. or non-dog typical helminth eggs) in dogs belonging
      to owners that did not report coprophagic behaviour in their dogs. Results
      indicate that coprophagy in dogs may result in an overestimation of the
      prevalence of patent helminth infections and that dogs may serve as a transport
      host for helminth eggs.

PMID- 24880648
TI  - Prevalence of Clonorchis sinensis infection in freshwater fishes in northeastern
      China.
AB  - The prevalence of Clonorchis sinensis infection in freshwater fishes was surveyed
      in Heilongjiang Province, northeastern China, between August 2011 and September
      2013. Thirteen species of freshwater fish (n=3221) and one species of shrimp
      (n=93) were collected from Songhua river, Nenjiang river and other lakes or ponds
      in 37 sites of 15 representative cities in Heilongjiang Province. They were
      individually examined by digestion technique, and the C. sinensis metacercariae
      were identified morphologically followed by confirmation using sequences of the
      second internal transcribed spacer of ribosomal DNA. Ten of the 13 examined
      species of freshwater fishes were infected with C. sinensis metacercariae, while
      all shrimps were negative. The overall prevalence of C. sinensis infection in
      3221 examined freshwater fishes was 19.96%, with 42.57% (272/639) in
      Pseudorasbora parva, 22.55% (83/368) in Hemicculter leuciclus, 20.44% (121/592)
      in Carassius auratus, 17.71% (68/384) in Saurogobio dabryi, 10.85% (23/212) in
      Rhodeus ocellatus, 10.54% (48/455) in Phoxinus lagowskii, 8.20% (21/256) in
      Perccottus glehnii, 6.25% (5/80) in Misgurnus anguillicaudatus, 4.55% (1/22) in
      Xenocypris davidi, and 1.49% (1/67) in Cyprinus carpio. The average infection
      intensity in P. parva was 103.3 encysted metacercariae per gram of fish meat in
      Zhaoyuan city. The average prevalence of C. sinensis infection in Songhua river,
      Nenjiang river and lakes or ponds were 31.96% (503/1574), 11.30% (102/903) and
      7.93% (59/744), respectively. The prevalence of C. sinensis infection in Zhaoyuan
      city (43.68%) was the highest among all sampling locations. These results
      revealed a high-prevalence of C. sinensis infection in freshwater fishes in
      Heilongjiang Province, northeastern China, posing significant public health
      concern. 

PMID- 24880650
TI  - Genetic variations in the KIR gene family may contribute to susceptibility to
      ankylosing spondylitis: a meta-analysis.
AB  - The present meta-analysis of relevant case-control studies was conducted to
      investigate the possible relationships between genetic variations in the killer
      cell immunoglobulin-like receptor (KIR) gene clusters of the human KIR gene
      family and susceptibility to ankylosing spondylitis (AS). The following
      electronic databases were searched for relevant articles without language
      restrictions: the Web of Science, the Cochrane Library Database, PubMed, EMBASE,
      CINAHL, the Chinese Biomedical Database (CBM) and Chinese National Knowledge
      Infrastructure (CNKI) databases, covering all papers published until 2013. STATA
      statistical software was adopted in this meta-analysis as well. We also
      calculated the crude odds ratios (OR) and its 95% confidence intervals (95 % CI).
      Seven case-control studies with 1,004 patients diagnosed with AS and 2,138
      healthy cases were implicated in our meta-analysis, and 15 genes in the KIR gene
      family were also evaluated. The results of our meta-analysis show statistical
      significance between the genetic variations in the KIR2DL1, KIR2DS4, KIR2DS5 and
      KIR3DS1 genes and an increased susceptibility to AS (KIR2DL1: OR 7.82, 95% CI
      3.87-15.81, P< 0.001; KIR2DS4: OR 1.91, 95% CI 1.16-3.13, P = 0.010; KIR2DS5:
      OR1.51, 95% CI 1.14-2.01, P = 0.004; KIR3DS1: OR 1.58, 95% CI 1.34-1.86, P<
      0.001; respectively). However, we failed to found positive correlations between
      other genes and susceptibility to AS (all P >0.05). The current meta-analysis
      provides reliable evidence that genetic variations in the KIR gene family may
      contribute to susceptibility to AS, especially for the KIR2DL1, KIR2DS4, KIR2DS5
      and KIR3DS1 genes.

PMID- 24880649
TI  - Maternal and fetal immune response patterns in heifers experimentally infected
      with Neospora caninum in the second trimester of pregnancy--a descriptive study.
AB  - Fetal and maternal immune responses 3, 6 and 9 weeks post infection (wpi) were
      investigated in cows experimentally infected with Neospora caninum on day 110 of
      gestation. Descriptive analysis showed that the fetuses had lower percentages of
      spleen T cell subpopulations (CD3+, CD4+ and CD8+) at 6 wpi compared to 3 wpi
      and/or 9 wpi, with the lowest percentages observed in a dead fetus found upon
      euthanasia at that time. Increased expression of most cytokines over levels
      recorded at 3 and 9 wpi were found in fetuses that were alive at 6 wpi. Up
      regulated Th1, Th2 and Treg expression was also observed at 6 wpi in the spleen
      and in the lymph nodes draining the placenta of the cows. At the placental level,
      while most cytokines were down-regulated from 6 wpi, up-regulation of IL-4
      expression was observed at 6 wpi in the caruncle. Our results suggest that the
      immune response at 6 wpi was crucial for fetal survival in this model of bovine
      neosporosis.

PMID- 24880651
TI  - [Eradication of Staphylococcus aureus in carrier patients undergoing joint
      arthroplasty].
AB  - INTRODUCTION: Prosthetic joint infection (PJI) is a complication with serious
      repercussions and its main cause is Staphylococcus aureus. The purpose of this
      study is to determine whether decolonization of S.aureus carriers helps to reduce
      the incidence of PJI by S.aureus. MATERIAL AND METHODS: An S.aureus screening
      test was performed on nasal carriers in patients undergoing knee or hip
      arthroplasty between January and December 2011. Patients with a positive test
      were treated with intranasal mupirocin and chlorhexidine soap 5 days. The
      incidence of PJI was compared with patients undergoing the same surgery between
      January and December 2010. RESULTS: A total of 393 joint replacements were
      performed in 391 patients from the control group, with 416 joint replacements
      being performed in the intervention group. Colonization study was performed in
      382 patients (91.8%), of which 102 were positive (26.7%) and treated. There was 2
      PJI due S.aureus compared with 9 in the control group (0.5% vs 2.3%, odds ratio
      [OR]: 0.2, 95% confidence interval [CI]: 0.4 to 2.3, P=.04). CONCLUSIONS: In our
      study, the detection of colonization and eradication of S.aureus carriers
      achieved a significant decrease in PJI due to S.aureus compared to a historical
      group.

PMID- 24880652
TI  - Malignant transformation of endometriosis and its clinical significance.

PMID- 24880653
TI  - Lag time from ovulation trigger to oocyte aspiration and oocyte maturity in
      assisted reproductive technology cycles: a retrospective study.
AB  - OBJECTIVE: To study the correlation between the lag time from ovulation trigger
      to oocyte aspiration and the proportion of metaphase II (MII) mature oocytes
      aspirated. DESIGN: Retrospective study. SETTING: Fertility and IVF center in an
      academic regional hospital. PATIENT(S): A total of 511 women undergoing IVF
      intracytoplasmic sperm injection at our center, with at least one oocyte
      available for maturity determination. INTERVENTION(S): Data were retrieved from
      patient electronic databases and files. Demographic data, hormone treatments and
      ovarian response, and the time of ovulation trigger and oocyte aspiration were
      recorded. MAIN OUTCOME MEASURE(S): The primary outcome was the proportion of MII
      mature oocytes relative to the total number of oocytes aspirated and allocated to
      intracytoplasmic sperm injection. Pregnancy rates and clinical pregnancy rates
      were secondary outcomes. RESULT(S): There were fewer MII mature oocytes when the
      lag time between oocyte trigger and aspiration was between 33.45 hours and 34.45
      hours. The proportion of MII oocytes seems to increase up to a 35-hour lag time
      and then stabilizes up to 38 hours. Pregnancy and clinical pregnancy rates did
      not differ among the different time groups studied. CONCLUSION(S): Oocyte
      aspiration should be scheduled at least 35 hours after ovulation trigger. Oocytes
      can be aspirated in a 3-hour window of time between 35 and 38 hours without
      compromising results. Further research should elucidate whether even longer lag
      times will improve the proportion of MII mature oocytes.

PMID- 24880654
TI  - Single-incision sling operations for urinary incontinence in women.
AB  - BACKGROUND: Urinary incontinence has been shown to affect up to 50% of women.
      Studies in the United States have shown that up to 80% of these women have an
      element of stress urinary incontinence. Colposuspension and now mid-urethral
      slings have been shown to be effective in treating patients with stress
      incontinence. However, associated adverse events include bladder and bowel
      injury, groin pain and haematoma formation. This has led to the development of
      third-generation single-incision slings, also referred to as mini-slings.It
      should be noted that TVT-Secur (Gynecare, Bridgewater, NJ, USA) is one type of
      single-incision sling; it has been withdrawn from the market because of poor
      results. However, it is one of the most widely studied single-incision slings and
      was used in several of the trials included in this review. Despite its withdrawal
      from clinical use, it was decided that data pertaining to this sling should be
      included in the first iteration of this review, so that level 1a data are
      available in the literature to confirm its lack of efficacy. OBJECTIVES: To
      assess the effectiveness of mini-sling procedures in women with urodynamic
      clinical stress or mixed urinary incontinence in terms of improved continence
      status, quality of life or adverse events. SEARCH METHODS: We searched the
      Cochrane Incontinence Group Specialised Trials Register, which contains trials
      identified from the Cochrane Central Register of Controlled Trials (CENTRAL),
      MEDLINE and MEDLINE in process; we handsearched journals and conference
      proceedings (searched 6 February 2013) and searched ClinicalTrials.gov (searched
      20 September 2012), the World Health Organization (WHO) International Clinical
      Trials Registry Platform (ICTRP) (searched 20 September 2012) and the reference
      lists of relevant articles. SELECTION CRITERIA: Randomised or quasi-randomised
      controlled trials in women with urodynamic stress incontinence, symptoms of
      stress incontinence or stress-predominant mixed urinary incontinence, in which at
      least one trial arm involves one of the new single-incision slings. The
      definition of a single-incision sling is "a sling that does not involve either a
      retropubic or transobturator passage of the tape or trocar and involves only a
      single vaginal incision (i.e. no exit wounds in the groin or lower abdomen)."
      DATA COLLECTION AND ANALYSIS: Three review authors assessed the methodological
      quality of potentially eligible trials and independently extracted data from the
      individual trials. MAIN RESULTS: We identified 31 trials involving 3290 women.
      Some methodological flaws were observed in some trials; a summary of these is
      given in the 'Risk of bias in included studies' section.No studies compared
      single-incision slings versus no treatment, conservative treatment,
      colposuspension, laparoscopic procedures or traditional sub-urethral slings. Also
      no data on the comparison of single-incision slings versus retropubic mid
      urethral slings (top-down approach) were available, but the review authors
      believe this did not affect the overall comparison versus retropubic mid-urethral
      slings.The types of single-incision slings included in this review were TVT-Secur
      (Gynecare), MiniArc (American Medical Systems, Minnetonka, MN, USA), Ajust (C.R.
      Bard, Inc.,Covington, GA, USA), Needleless (Mayumana Healthcare, Lisse, The
      Netherlands), Ophira (Promedon, Cordoba, Argentina), Tissue Fixation System (TFS
      PTY Ltd, Sydney, Australia) and CureMesh (D.Med. Co., Inc., Seoul, Korea).Women
      were more likely to remain incontinent after surgery with single-incision slings
      than with retropubic slings such as tension-free vaginal tape (TVT(TM)) (121/292,
      41% vs 72/281, 26%; risk ratio (RR) 2.08, 95% confidence interval (CI) 1.04 to
      4.14). Duration of the operation was slightly shorter for single-incision slings
      but with higher risk of de novo urgency (RR 2.39, 95% CI 1.25 to 4.56). Four of
      five studies in the comparison included TVT-Secur as the single-incision
      sling.Single-incision slings resulted in higher incontinence rates compared with
      inside-out transobturator slings (30% vs 11%; RR 2.55, 95% CI 1.93 to 3.36). The
      adverse event profile was significantly worse, specifically consisting of higher
      risks of vaginal mesh exposure (RR 3.75, 95% CI 1.42 to 9.86), bladder/urethral
      erosion (RR 17.79, 95% CI 1.06 to 298.88) and operative blood loss (mean
      difference 18.79, 95% CI 3.70 to 33.88). Postoperative pain was less common with
      single-incision slings (RR 0.29, 95% CI 0.20 to 0.43), and rates of long-term
      pain or discomfort were marginally lower, but the clinical significance of these
      differences is questionable. Most of these findings were derived from the trials
      involving TVT-Secur: Excluding the other trials showed that high risk of
      incontinence was principally associated with use of this device (RR 2.65, 95% CI
      1.98 to 3.54). It has been withdrawn from clinical use.Evidence was insufficient
      to reveal a difference in incontinence rates with other single-incision slings
      compared with inside-out or outside-in transobturator slings. Duration of the
      operation was marginally shorter for single-incision slings compared with
      transobturator slings, but only by approximately two minutes and with significant
      heterogeneity in the comparison. Risks of postoperative and long-term groin/thigh
      pain were slightly lower with single-incision slings, but overall evidence was
      insufficient to suggest a significant difference in the adverse event profile for
      single-incision slings compared with transobturator slings. Evidence was also
      insufficient to permit a meaningful sensitivity analysis of the other single
      incision slings compared with transobturator slings, as all confidence intervals
      were wide. The only significant differences were observed in rates of
      postoperative and long-term pain, and in duration of the operation, which
      marginally favoured single-incision slings.Overall results show that TVT-Secur is
      considerably inferior to retropubic and inside-out transobturator slings, but
      additional evidence is required to allow any reasonable comparison of other
      single-incision slings versus transobturator slings.When one single-incision
      sling was compared with another, evidence was insufficient to suggest a
      significant difference between any of the slings in any of the comparisons made.
      AUTHORS' CONCLUSIONS: TVT-Secur is inferior to standard mid-urethral slings for
      the treatment of women with stress incontinence and has already been withdrawn
      from clinical use. Not enough evidence has been found on other single-incision
      slings compared with retropubic or transobturator slings to allow reliable
      comparisons. Additional adequately powered and high-quality trials with longer
      term follow-up are required. Trials should clearly describe the fixation
      mechanism of these single-incisions slings: It is apparent that, although clubbed
      together as a single group, a significant difference in fixation mechanisms may
      influence outcomes.

PMID- 24880655
TI  - Development of a microchip Europium nanoparticle immunoassay for sensitive point
      of-care HIV detection.
AB  - Rapid, sensitive and specific diagnostic assays play an indispensable role in
      determination of HIV infection stages and evaluation of efficacy of
      antiretroviral therapy. Recently, our laboratory developed a sensitive Europium
      nanoparticle-based microtiter-plate immunoassay capable of detecting target
      analytes at subpicogram per milliliter levels without the use of catalytic
      enzymes and signal amplification processes. Encouraged by its sensitivity and
      simplicity, we continued to miniaturize this assay to a microchip platform for
      the purpose of converting the benchtop assay technique to a point-of-care test.
      It was found that detection capability of the microchip platform could be readily
      improved using Europium nanoparticle probes. We were able to routinely detect 5
      pg/mL (4.6 attomoles) of HIV-1 p24 antigen at a signal-to-blank ratio of 1.5, a
      sensitivity level reasonably close to that of microtiter-plate Europium
      nanoparticle assay. Meanwhile, use of the microchip platform effectively reduced
      sample/reagent consumption 4.5 fold and shortened total assay time 2 fold in
      comparison with microtiter plate assays. Complex matrix substance in plasma
      negatively affected the microchip assays and the effects could be minimized by
      diluting the samples before loading. With further improvements in sensitivity,
      reproducibility, usability, assay process simplification, and incorporation of
      portable time-resolved fluorescence reader, Europium nanoparticle immunoassay
      technology could be adapted to meet the challenges of point-of-care diagnosis of
      HIV or other health-threatening pathogens at bedside or in resource-limited
      settings.

PMID- 24880656
TI  - Tuneable surface shear forces to physically displace nonspecific molecules in
      protein biomarker detection.
AB  - We report a simple method to remove nonspecifically adsorbed species from sensor
      surface and also improve the detection sensitivity of the sensor using tuneable
      alternating current (ac) electrohydrodynamics (ac-EHD) forces. These forces
      generated within few nanometers of an electrode surface (i.e., double layer)
      engender fluid flow within a serpentine channel containing a long array of the
      asymmetric electrode pairs, and can easily be tuned externally by changing the
      frequency and amplitude of the ac-EHD field. Under the optimized experimental
      conditions, we achieved a 3.5-fold reduction in nonspecific adsorption of non
      target proteins with a 1000-fold enhancement in detection sensitivity of the
      device for the analysis of human epidermal growth factor receptor 2 (HER2)
      protein spiked in serum. This approach can be applicable in diverse fields
      including biosensors, cellular and molecular separation systems and biomedical
      applications to remove/reduce nonspecific adsorption of molecular and cellular
      species. 

PMID- 24880657
TI  - Polymer-based, flexible glutamate and lactate microsensors for in vivo
      applications.
AB  - We present a flexible microsensor, based on a polymer substrate, for
      multiparametric, electrochemical in vivo monitoring. The sensor strip with a
      microelectrode array at the tip was designed for insertion into tissue, for fast
      and localized online monitoring of physiological parameters. The microsystem
      fabrication on a wafer-level is based on a polyimide substrate and includes the
      patterning of platinum microelectrodes as well as epoxy and dry-film-resist
      insulation in a cost-effective thin-film and laminate process. A stable,
      electrodeposited silver/silver chloride reference electrode on-chip and a perm
      selective membrane as an efficient interference rejection scheme are integrated
      on a wafer-level. Amperometric, electrochemical, enzyme-based biosensors for the
      neurotransmitter L-glutamate and the energy metabolite L-lactate have been
      developed. Hydrogel membranes or direct cross-linking as stable concepts for the
      enzyme immobilization are shown. Sensor performance including high selectivity,
      tailoring of sensitivity and long-term stability is discussed. For glutamate, a
      high sensitivity of 2.16 nAmm(-2) uM(-1) was found. For lactate, a variation in
      sensitivity between 2.6 and 32 nAmm(-2)mM(-1) was achieved by different membrane
      compositions. The in vivo application in an animal model is demonstrated by
      glutamate measurements in the brain of rats. Local glutamate alterations in the
      micromolar range and in nanoliter-range volumes can be detected and quantified
      with high reproducibility and temporal resolution. A novel, versatile platform
      for the integration of various electrochemical sensors on a small, flexible
      sensor strip for a variety of in vivo applications is presented.

PMID- 24880658
TI  - They are not always a burden: older people and child fostering in Uganda during
      the HIV epidemic.
AB  - This qualitative study examines the role of older people (60 years and above) in
      fostering decisions for orphans and non-orphans within extended families in a
      rural Ugandan community heavily affected by HIV. Fieldwork conducted in 2006
      provided information on the influence of HIV on fostering decisions through 48
      individual in-depth interviews and two group interviews with foster-children and
      family members to develop detailed case studies related to 13 fostered
      adolescents. The adolescents included five non-orphans and eight orphans (five
      were double orphans because they had lost both parents). Older people play a very
      important role in fostering decisions as potential foster-parents, advisers,
      mediators and gatekeepers. They have a high level of authority over the foster
      children, who are regarded as important resources within the extended family.
      With fewer potential caregivers available because of HIV-related deaths, the
      responsibility for fostering orphans has often fallen to surviving older people.
      Fostering is used by older people and the child's extended family as a strategy
      to ensure the welfare of the foster-child. When the foster-parent is an older
      person, it is also used to ensure physical and emotional support for the older
      person themselves. Support from the extended family towards foster households is
      widely reported to have been reduced by HIV by diminishing resources that would
      otherwise have been made available to support foster care. New initiatives and
      investment are required to complement community and family resources within well
      managed social protection and welfare programmes. To be effective, such
      programmes will require adequate investment in administrative capacity and
      monitoring. They must aim to strengthen families and, recognizing that resources
      are limited, should prioritize the community's poorest households, rather than
      specifically targeting households with orphans or other foster-children. 

PMID- 24880659
TI  - Codifying knowledge to improve patient safety: a qualitative study of practice
      based interventions.
AB  - Although it is well established that health care professionals use tacit and
      codified knowledge to provide front-line care, less is known about how these two
      forms of knowledge can be combined to support improvement related to patient
      safety. Patient safety interventions involving the codification of knowledge were
      co-designed by university and hospital-based staff in two English National Health
      Service (NHS) hospitals to support the governance of medication safety and
      mortality and morbidity (M&M) meetings. At hospital A, a structured mortality
      review process was introduced into three clinical specialities from January to
      December 2010. A qualitative approach of observing M&M meetings (n = 30) and
      conducting interviews (n = 40) was used to examine the impact on meetings and on
      front-line clinicians and hospital managers. At hospital B, a medication safety
      'scorecard' was administered on a general medicine and elderly care ward from
      September to November 2011. Weekly feedback meetings were observed (n = 18) and
      interviews with front-line staff conducted (n = 10) to examine how knowledge
      codification influenced behaviour. Codification was shown to support learning
      related to patient safety at the micro (front-line service) level by structuring
      the sharing of tacit knowledge, but the presence of professional and managerial
      boundaries at the organisational level affected the codification initiatives'
      implementation. The findings suggest that codifying knowledge to support
      improvement presents distinct challenges at the group and organisational level;
      translating knowledge across these levels is contingent on the presence of
      enabling organisational factors, including the alignment of learning from
      clinical practice with its governance.

PMID- 24880661
TI  - FGFR3 mutations, but not FGFR3 expression and FGFR3 copy-number variations, are
      associated with favourable non-muscle invasive bladder cancer.
AB  - The fibroblast growth factor receptor 3 (FGFR3) is a tyrosine kinase receptor
      frequently activated by point mutations in bladder cancer (BC). These mutations
      are associated with genetically stable, Ta and low-grade BC, representing the
      favourable BC pathway. Conversely, FGFR3 over-expression was recently found in 40
      % of muscle invasive BC. We examined FGFR3 mutation status and protein expression
      in patients originally diagnosed as T1. We also investigated copy-number
      variations in FGFR3 as a possible alternative mechanism to activate FGFR3. We
      included 84 patients with T1 BC as their initial diagnosis. A uropathologist
      reviewed the slides for grade and (sub)stage. The FGFR3 mutation status was
      examined by PCR-SNaPshot and FGFR3 protein expression by standard immuno
      histochemistry (FGFR3-B9). Copy-number status was determined in 69/84 cases with
      nine probes covering nine exons of the FGFR3 gene (MLPA). Of 27 BC with FGFR3
      mutations, 26 (96 %) showed FGFR3 over-expression. Of the 57 wild-type BC, 27 (47
      %) BC showed over-expression. Pathological parameters significantly differed (p <
      0.01) between mutant and wild-type tumours with the FGFR3 mutation pointing to
      more favourable BC. However, if the BC exhibited wild-type FGFR3, FGFR3 protein
      status had no influence on grade and (sub)stage. We found six tumours with more
      than or equal to three copies of FGFR3. Only 1 of 22 wild-type tumours with over
      expression of FGFR3 had more than or equal to three gene copies. In initially
      diagnosed T1 BC, only the FGFR3 mutation was significantly associated with
      favourable BC disease characteristics. In addition to almost all FGFR3 mutant BC,
      47 % of wild-type BC displayed FGFR3 over-expression, suggesting an alternative
      mechanism to activate FGFR3. Increased FGFR3 copy number was a rare event and did
      not account for this mechanism. Nevertheless, FGFR3 wild-type tumours with over
      expression of the protein may still represent a subset that might potentially
      benefit from FGFR3-targeted therapy.

PMID- 24880663
TI  - The role of skin trauma in the distribution of morphea lesions: a cross-sectional
      survey of the Morphea in Adults and Children cohort IV.
AB  - BACKGROUND: Skin trauma may play a role in the development of morphea lesions.
      The association between trauma and the distribution of cutaneous lesions has
      never been examined to our knowledge. OBJECTIVE: We sought to determine whether
      patients enrolled in the Morphea in Adults and Children (MAC) cohort exhibit skin
      lesions distributed in areas of prior (isotopic) or ongoing (isomorphic) trauma.
      METHODS: This was a cross-sectional analysis of the MAC cohort. RESULTS: Of 329
      patients in the MAC cohort, 52 (16%) had trauma-associated lesions at the onset
      of disease. Patients with lesions in an isotopic distribution had greater
      clinical severity as measured by a clinical outcome measure (mean modified Rodnan
      Skin Score of 13.8 vs 5.3, P = .004, 95% confidence interval 3.08-13.92) and
      impact on life quality (mean Dermatology Life Quality Index score 8.4 vs 4.1, P =
      .009, 95% confidence interval 1.18-7.50) than those with an isomorphic
      distribution. Most frequent associated traumas were chronic friction (isomorphic)
      and surgery/isotopic. LIMITATIONS: Recall bias for patient-reported events is a
      limitation. CONCLUSION: Of patients in the MAC cohort, 16% developed initial
      morphea lesions at sites of skin trauma. If these findings can be confirmed in
      additional series, they suggest that elective procedures and excessive skin
      trauma or friction might be avoided in these patients.

PMID- 24880662
TI  - Computationally driven deletion of broadly distributed T cell epitopes in a
      biotherapeutic candidate.
AB  - Biotherapeutics are subject to immune surveillance within the body, and anti
      biotherapeutic immune responses can compromise drug efficacy and patient safety.
      Initial development of targeted antidrug immune memory is coordinated by T cell
      recognition of immunogenic subsequences, termed "T cell epitopes."
      Biotherapeutics may therefore be deimmunized by mutating key residues within
      cognate epitopes, but there exist complex trade-offs between immunogenicity,
      mutational load, and protein structure-function. Here, a protein deimmunization
      algorithm has been applied to P99 beta-lactamase, a component of antibody
      directed enzyme prodrug therapies. The algorithm, integer programming for
      immunogenic proteins, seamlessly integrates computational prediction of T cell
      epitopes with both 1- and 2-body sequence potentials that assess protein
      tolerance to epitope-deleting mutations. Compared to previously deimmunized P99
      variants, which bore only one or two mutations, the enzymes designed here contain
      4-5 widely distributed substitutions. As a result, they exhibit broad reductions
      in major histocompatibility complex recognition. Despite their high mutational
      loads and markedly reduced immunoreactivity, all eight engineered variants
      possessed wild-type or better catalytic activity. Thus, the protein design
      algorithm is able to disrupt broadly distributed epitopes while maintaining
      protein function. As a result, this computational tool may prove useful in
      expanding the repertoire of next-generation biotherapeutics.

PMID- 24880664
TI  - Hidradenitis suppurativa: a retrospective study of 846 Dutch patients to identify
      factors associated with disease severity.
AB  - BACKGROUND: Few comprehensive studies exist on the epidemiology of hidradenitis
      suppurativa, a very distressing skin disease. OBJECTIVE: We sought to identify
      disease-related factors associated with severity, sex, and family history.
      METHODS: Ordinal logistic regression was used in 846 consecutive Dutch patients
      with hidradenitis suppurativa to calculate odds ratios (ORs) for severity
      according to Hurley. Sex and family history were compared using Student t test
      and chi(2) test. RESULTS: In total, 45.5% of the patients had Hurley I, 41.5% had
      Hurley II, and 13.0% had Hurley III. Severity was associated with male sex (OR
      2.11; P < .001), disease duration (OR 1.03; P < .001), body mass index (OR 1.03;
      P = .01), smoking pack-years (OR 1.02; P = .001), and axillary (OR 2.24; P <
      .001), perianal (OR 1.92; P < .001), and mammary lesions (OR 1.48; P = .03).
      Women had earlier onset, more inguinal and mammary lesions, and more frequent
      family history for hidradenitis suppurativa. Men more commonly had gluteal,
      perianal, and atypical lesions, and a history of severe acne. Patients with a
      family history had earlier onset, longer disease duration, a history of severe
      acne, more extensive disease, and were more often smokers. LIMITATIONS: Some
      parameters were patient-reported. CONCLUSION: The severity risk factors
      identified in this study could help physicians to select patients who need close
      monitoring and who would benefit from early, aggressive therapy.

PMID- 24880665
TI  - Meta-analysis comparing efficacy of antibiotics versus oral contraceptives in
      acne vulgaris.
AB  - BACKGROUND: Both antibiotics and oral contraceptive pills (OCPs) have been found
      to be effective in managing acne vulgaris. Despite widespread use, few direct
      comparisons of efficacy between the 2 modalities have been published. OBJECTIVE:
      We compared the efficacy of antibiotics and OCPs in managing acne. METHODS: A
      meta-analysis was conducted in accordance with Preferred Reporting Items for
      Systematic Reviews and Meta-Analyses and Cochrane collaboration guidelines.
      RESULTS: A review of 226 publications yielded 32 randomized controlled trials
      that met our inclusion criteria. At 3 and 6 months, compared with placebo, both
      antibiotics and OCPs effected greater percent reduction in inflammatory,
      noninflammatory, and total lesions; the 2 modalities at each time point
      demonstrated statistical parity, except that antibiotics were superior to OCPs in
      percent reduction of total lesions at 3 months (weighted mean inflammatory lesion
      reduction: 3-month course of oral antibiotic treatment = 53.2%, 3-month course of
      OCPs = 35.6%, 3-month course of placebo treatment = 26.4%, 6-month course of oral
      antibiotic treatment = 57.9%, 6-month course of OCPs = 61.9%, 6-month course of
      placebo treatment = 34.2%; weighted mean noninflammatory lesion reduction: 3
      month course of oral antibiotic treatment = 41.9%, 3-month course of OCPs =
      32.6%, 3-month course of placebo treatment = 17.1%, 6-month course of oral
      antibiotic treatment = 56.4%, 6-month course of OCPs = 49.1%, 6-month course of
      placebo treatment = 23.4%; weighted mean total lesion reduction: 3-month course
      of oral antibiotic treatment = 48.0%, 3-month course of OCPs = 37.3%, 3-month
      course of placebo treatment = 24.5%, 6-month course of oral antibiotic treatment
      = 52.8%, 6-month course of OCPs = 55.0%, 6-month course of placebo treatment =
      28.6%). LIMITATIONS: Investigative treatment heterogeneity and publication bias
      are limitations. CONCLUSIONS: Although antibiotics may be superior at 3 months,
      OCPs are equivalent to antibiotics at 6 months in reducing acne lesions and,
      thus, may be a better first-line alternative to systemic antibiotics for long
      term acne management in women.

PMID- 24880666
TI  - Colon cancer cells colonize the lung from established liver metastases through
      p38 MAPK signalling and PTHLH.
AB  - The mechanisms that allow colon cancer cells to form liver and lung metastases,
      and whether KRAS mutation influences where and when metastasis occurs, are
      unknown. We provide clinical and molecular evidence showing that different MAPK
      signalling pathways are implicated in this process. Whereas ERK2 activation
      provides colon cancer cells with the ability to seed and colonize the liver,
      reduced p38 MAPK signalling endows cancer cells with the ability to form lung
      metastasis from previously established liver lesions. Downregulation of p38 MAPK
      signalling results in increased expression of the cytokine PTHLH, which
      contributes to colon cancer cell extravasation to the lung by inducing caspase
      independent death in endothelial cells of the lung microvasculature. The
      concerted acquisition of metastatic traits in the colon cancer cells together
      with the sequential colonization of liver and lung highlights the importance of
      metastatic lesions as a platform for further dissemination. 

PMID- 24880667
TI  - FHOD1 interaction with nesprin-2G mediates TAN line formation and nuclear
      movement.
AB  - Active positioning of the nucleus is integral to division, migration and
      differentiation of mammalian cells. Fibroblasts polarizing for migration orient
      their centrosomes by actin-dependent nuclear movement. This nuclear movement
      depends on nesprin-2 giant (N2G), a large, actin-binding outer nuclear membrane
      component of transmembrane actin-associated (TAN) lines that couple nuclei to
      moving actin cables. Here, we identify the diaphanous formin FHOD1 as an
      interaction partner of N2G. Silencing FHOD1 expression or expression of fragments
      containing binding sites for N2G or FHOD1 disrupted nuclear movement and
      centrosome orientation in polarizing fibroblasts. Unexpectedly, silencing of
      FHOD1 expression did not affect the formation or rearward flow of dorsal actin
      cables required for nuclear positioning. Rather, N2G-FHOD1 interaction provided a
      second connection to actin cables essential for TAN line formation and thus
      nuclear movement. These results reveal a unique function for a formin in coupling
      an organelle to actin filaments for translocation, and suggest that TAN lines
      require multi-point attachments to actin cables to resist the large forces
      necessary to move the nucleus.

PMID- 24880668
TI  - Hypercholesterolemia increases plasma saturated and n-6 fatty acids altering
      prostaglandin homeostasis and promotes endothelial dysfunction in rabbits.
AB  - The present study evaluated the plasma fatty acid levels and the vascular
      prostaglandin (PG) release in a rabbit model of early hypercholesterolemia with
      endothelial dysfunction. Rabbits were fed either a control diet (CD) or a diet
      containing 1 % cholesterol (HD) for 5-6 weeks. The level of fatty acids was
      measured in plasma. The levels of PG and nitric oxide (NO) released from the
      aorta were also determined. Vascular morphology of the aorta was characterized by
      intima and media thickness measurements. The rabbits fed with HD had higher
      levels of arachidonic acid (ARA) and lower levels of oleic acid. The linoleic
      acid level was unchanged. PGI(2) and NO were diminished and PGF(2alpha) levels,
      the PGI(2)/TXA(2) ratio and the intima/media ratio were increased in rabbits fed
      with HD. In conclusion, feeding HD for a short period increased ARA plasma levels
      and unbalanced release of vasodilator/vasoconstrictor PG redirected the pathway
      to vasoconstrictor metabolite release. These lipid metabolism alterations in
      addition to the reduced NO levels and the moderate changes in the vascular
      morphology contributed to the endothelial dysfunction in this animal model.
      Therefore, the present findings support the importance of early correction or
      prevention of high cholesterol levels to disrupt the endothelial dysfunction
      process that leads to cardiovascular disease.

PMID- 24880669
TI  - HIP-55 negatively regulates myocardial contractility at the single-cell level.
AB  - Myocardial contractility is crucial for cardiac output and heart function. But
      the detailed mechanisms of regulation remain unclear. In the present study, we
      found that HIP-55, an actin binding protein, negatively regulates myocardial
      contractility at the single-cell level. HIP-55 was overexpressed and knocked down
      in cardiomyocytes with an adenovirus infection. The traction forces exerted by
      single cardiomyocyte were measured using cell traction force microscopy. The
      results showed that HIP-55 knockdown significantly increased the contractility of
      the cardiomyocytes and HIP-55 overexpression could markedly reverse this process.
      Furthermore, HIP-55 was obviously co-localized with F-actin in cardiomyocytes,
      suggesting that HIP-55 regulated cardiac contractile function through the
      interaction between HIP-55 and F-actin. This study reveals the regulatory
      mechanisms of myocardial contractility and provides a new target for preventing
      and treating cardiovascular disease. 

PMID- 24880670
TI  - Evaluation of the health-related quality of life for patients following
      laparoscopic cholecystectomy.
AB  - PURPOSE: Laparoscopic cholecystectomy (LC) has become the standard procedure, and
      contributes to a shorter hospital stay. However, there have been no reports
      regarding when the patients can be discharged in terms of their health-related
      quality of life (HRQOL). METHODS: The HRQOL was evaluated by using the SF-8
      health survey (SF-8) 24-hour version in 127 consecutive patients treated from May
      2007 to December 2008. The HRQOL and a visual analogue scale (VAS) score were
      assessed on the day before surgery and on postoperative day (POD) 1, POD2 and
      POD7. RESULTS: All scores of the eight domains on POD1 were significantly
      decreased compared to the preoperative score (P < 0.05), and seven scores were
      still decreased on POD2, with the mental health (MH) domain showing an
      improvement. On POD7, the general health score improved to the preoperative
      level. The physical component summary 8 (PCS-8) was suppressed for all 7 days
      after LC. The mental health component summary 8 (MCS-8) was improved to the
      preoperative level on POD2, despite the significant suppression observed on POD1
      (P < 0.05). The VAS score was higher in the low PCS-8 (PCS-8 < 42.4) and low MCS
      8 (MCS-8 < 40.6) patients than in the high PCS-8 and high MCS-8 patients.
      CONCLUSION: The HRQOL score demonstrated the improvement of the MCS-8 on POD2,
      which might suggest that a discharge of LC patients is appropriate on POD2 in
      terms of the patients' point of view.

PMID- 24880672
TI  - Acoustic analysis of four common voice diagnoses: moving toward disorder-specific
      assessment.
AB  - OBJECTIVES: To assess treatment outcomes via acoustic voice laboratory
      measurements before and after intervention in patients with common voice problems
      and Determine if outcome sensitivity of certain voice laboratory measures varies
      with disorder type. STUDY DESIGN: Retrospective and single-blinded. METHODS: In
      this study, 40 patients with a single voice disorder diagnosis of either benign
      vocal fold lesions (lesions), primary muscle tension dysphonia (MTD-1), vocal
      fold atrophy (atrophy) or unilateral vocal fold paralysis (UVFP) underwent
      baseline testing, a single intervention-type (phonosurgery/voice therapy), and
      follow-up testing at uniform time points. Ten patients per diagnosis group were
      analyzed before and after treatment. Time- and frequency-based acoustic measures
      taken from vowels and sentences as well as patient-perceptual analysis (Voice
      Handicap Index-10) were reviewed. RESULTS: Statistically significant improvements
      were observed for three of four groups. Patients with muscle tension dysphonia
      displayed an improvement in Cepstral Spectral Index of Dysphonia speech (CSID) (P
      < 0.05). Patients with lesions had improved Voice Handicap Index-10 (P < 0.05),
      cepstral peak prominence (CPP) vowel standard deviation (P < 0.05), and CPP
      speech (P < 0.05). Patients with atrophy did not demonstrate significant
      improvement in any measure. Patients with unilateral vocal fold paralysis showed
      an improvement in CSID speech (P < 0.05) and CPP speech (P < 0.05). In addition,
      strong effect sizes were observed for many of the acoustic parameters studied.
      CONCLUSIONS: For all groups except atrophy, treatment was successful in improving
      patient perception of voice handicap and/or some acoustic voice parameters. A
      disorder-specific response to frequency-based acoustic measures was found.

PMID- 24880671
TI  - Risk factors for bowel necrosis in patients with hepatic portal venous gas.
AB  - PURPOSE: To evaluate the risk factors for bowel necrosis in adult patients with
      hepatic portal venous gas (HPVG). METHODS: This retrospective study comprised 33
      adult patients treated for HPVG between August, 2008 and December, 2011. The
      patients were divided into a necrotic group (n = 14) and a non-necrotic group (n
      = 19). We analyzed the clinical demographics, laboratory data, multi-detector
      computed tomography findings, treatments, and outcomes in each group. RESULTS:
      Abdominal pain, peritoneal signs, systolic blood pressure, aspartate
      aminotransferase, alanine aminotransferase, lactate dehydrogenase (LDH), small
      intestinal dilatation, poor enhancement of the bowel wall, and intestinal
      pneumatosis were all significantly associated with bowel necrosis. Moreover,
      there were significantly more operative cases and deaths in the necrotic group.
      Multivariate analysis revealed that systolic BP (p = 0.048), LDH (p = 0.022), and
      intestinal pneumatosis (p = 0.038) were independent risk factors for bowel
      necrosis. Thus, we created new diagnostic criteria for bowel necrosis based on
      these three factors, the sensitivity, specificity, and accuracy of which were
      100, 78.9, and 87.9 %, respectively. CONCLUSIONS: This study demonstrates new and
      important findings to evaluate the risk factors for bowel necrosis. Using our
      diagnostic criteria, the indications for emergency laparotomy can be established
      more accurately.

PMID- 24880673
TI  - Surface-evoked laryngeal sensory action potential evaluation in neurogenic
      chronic cough.
AB  - OBJECTIVES: Neurogenic chronic cough is currently a diagnosis of exclusion. We
      hypothesized that surface-evoked laryngeal sensory action potential (SELSAP)
      testing could be used to help establish a diagnosis of laryngeal sensory
      neuropathy as a cause of chronic cough, based on altered SELSAP waveform
      morphology. STUDY DESIGN: Retrospective cohort study. METHODS: Laryngeal
      electromyographic (EMG) data including SELSAP waveform testing from patients with
      chronic cough were directly compared with a control population without
      significant laryngeal symptoms, and statistical analysis of unilateral and
      bilateral neuropathy injury subgroups was performed. RESULTS: Thirty patients
      with a chief complaint of chronic cough underwent laryngeal EMG testing since
      January 2000 with needle EMG and surface nerve conduction studies. SELSAP
      waveform analysis of unilateral and bilateral laryngeal neuropathy demonstrated
      significantly lowered median SELSAP peak amplitude compared with controls (P <
      0.01). CONCLUSIONS: Patients with suspected neurogenic chronic cough demonstrate
      statistically significant alterations in SELSAP waveform that can support a
      diagnosis of laryngeal sensory neuropathy.

PMID- 24880674
TI  - Systemic hydration: relating science to clinical practice in vocal health.
AB  - OBJECTIVES: To examine the current state of the science regarding the role of
      systemic hydration in vocal function and health. STUDY DESIGN: Literature review.
      METHODS: Literature search spanning multiple disciplines, including speech
      language pathology, nutrition and dietetics, medicine, sports and exercise
      science, physiology, and biomechanics. RESULTS: The relationship between
      hydration and physical function is an area of common interest among multiple
      professions. Each discipline provides valuable insight into the connection
      between performance and water balance, as well as complimentary methods of
      investigation. Existing voice literature suggests a relationship between
      hydration and voice production; however, the underlying mechanisms are not yet
      defined and a treatment effect for systemic hydration remains to be demonstrated.
      Literature from other disciplines sheds light on methodological shortcomings and,
      in some cases, offers an alternative explanation for observed phenomena.
      CONCLUSIONS: A growing body of literature in the field of voice science is
      documenting a relationship between hydration and vocal function; however, greater
      understanding is required to guide best practice in the maintenance of vocal
      health and management of voice disorders. Integration of knowledge and technical
      expertise from multiple disciplines facilitates analysis of existing literature
      and provides guidance as to future research.

PMID- 24880675
TI  - Classification of vocal aging using parameters extracted from the glottal signal.
AB  - This article proposes and evaluates a method to classify vocal aging using
      artificial neural network (ANN) and support vector machine (SVM), using the
      parameters extracted from the speech signal as inputs. For each recorded speech,
      from a corpus of male and female speakers of different ages, the corresponding
      glottal signal is obtained using an inverse filtering algorithm. The Mel
      Frequency Cepstrum Coefficients (MFCC) also extracted from the voice signal and
      the features extracted from the glottal signal are supplied to an ANN and an SVM
      with a previous selection. The selection is performed by a wrapper approach of
      the most relevant parameters. Three groups are considered for the aging-voice
      classification: young (aged 15-30 years), adult (aged 31-60 years), and senior
      (aged 61-90 years). The results are compared using different possibilities: with
      only the parameters extracted from the glottal signal, with only the MFCC, and
      with a combination of both. The results demonstrate that the best classification
      rate is obtained using the glottal signal features, which is a novel result and
      the main contribution of this article. 

PMID- 24880676
TI  - Protein tyrosine phosphatase non-receptor type 22 (PTPN22) +1858 C>T gene
      polymorphism in Egyptian cases with rheumatoid arthritis.
AB  - BACKGROUND: Rheumatoid arthritis (RA) is a common autoimmune disease with a
      complex genetic background. The gene encoding protein tyrosine phosphatase non
      receptor type 22 (PTPN22) has been reported to be associated with RA in several
      populations. OBJECTIVES: This work aimed at assessing the association of PTPN22
      +1858 C>T gene polymorphism with the susceptibility, activity and severity of RA
      in Egyptian subjects. SUBJECTS AND METHODS: This study included 112 unrelated RA
      patients who were compared to 122 healthy unrelated individuals taken from the
      same locality. For all subjects, DNA was genotyped for PTPN22 +1858 C>T
      (rs2476601) polymorphism using the PCR-RFLP technique. Antibodies to cyclic
      citrullinated peptides (anti-CCP) were measured by enzyme-linked immunosorbent
      assay (ELISA). RESULTS: Cases showed significantly higher PTPN22 +1858 T allele
      carriage rate (CT+TT genotypes) compared to controls (34.8% vs. 8.2%, OR=5.98,
      95% CI=2.81-12.73, p<0.001). Also the frequency of the PTPN22 +1858 T allele was
      significantly higher among cases compared to controls (18.7% vs. 4.5%, OR=4.89;
      95% CI=2.45-9.76, p<0.001). Cases positive to the PTPN22 T allele (CT+TT
      genotypes) showed no significant difference from those with the CC genotype
      regarding clinical and immune parameters. Nonetheless, they showed a more
      functional disability presented in their significantly higher health assessment
      questionnaire (HAQ) score (p=0.04). CONCLUSIONS: This study is a confirmatory
      evidence of the association of the PTPN22 +1858 T allele with susceptibility and
      functional disability of RA in Egyptian subjects.

PMID- 24880677
TI  - Vitamin D receptor TaqI and ApaI polymorphisms: a comparative study in patients
      with Behcet's disease and Rheumatoid arthritis in Tunisian population.
AB  - Recent genetic surveys have identified vitamin D receptor (VDR) as a
      susceptibility gene for several autoimmune diseases. This study was designed to
      investigate the association of VDR gene polymorphisms with Behcet's disease (BD)
      and Rheumatoid arthritis (RA). A case-control study including 151 BD, 106 RA
      patients and an appropriate number of healthy control subjects were performed
      using polymerase chain reaction (PCR) and restriction fragment length
      polymorphism (RFLP) techniques. Association between TaqI polymorphism and BD was
      marginal under codominant and recessive models (P=0.078 and P=0.058,
      respectively). After stratification, we found evidence for a significant
      association between TaqI polymorphism and BD in the elderly subjects (P=0.037).
      The minor ApaI a allele tended to confer an increased risk for BD susceptibility
      (P=0.087). BD patients with VDR homozygous AA or aa genotypes were at increased
      risk for development of erythema nodosum (EN) skin manifestation (P=0.038). No
      significant association was observed for VDR ApaI and TaqI polymorphisms with RA
      risk (P>0.05). TaqI and ApaI polymorphisms might be modestly implicated in BD
      pathogenesis. They could be considered as potential biomarkers in BD rather than
      susceptibility genes. However, TaqI and ApaI seemed not to be implicated in RA
      pathogenesis.

PMID- 24880678
TI  - Analysis of the EBT3 Gafchromic film irradiated with 6 MV photons and 6 MeV
      electrons using reflective mode scanners.
AB  - We explore in our study the effects of electrons and X-rays irradiations on the
      newest version of the Gafchromic EBT3 film. Experiments are performed using the
      Varian "TrueBeam 1.6" medical accelerator delivering 6 MV X-ray photons and 6 MeV
      electron beams as desired. The main interest is to compare the responses of EBT3
      films exposed to two separate beams of electrons and photons, for radiation doses
      ranging up to 500 cGy. The analysis is done on a flatbed EPSON 10000 XL scanner
      and cross checked on a HP Scanjet 4850 scanner. Both scanners are used in
      reflection mode taking into account landscape and portrait scanning positions.
      After thorough verifications, the reflective scanning method can be used on EBT3
      as an economic alternative to the transmission method which was also one of the
      goals of this study. A comparison is also done between single scan configuration
      including all samples in a single A4 (HP) or A3 (EPSON) format area and multiple
      scan procedure where each sample is scanned separately on its own. The images
      analyses are done using the ImageJ software. Results show significant influence
      of the scanning configuration but no significant differences between electron and
      photon irradiations for both single and multiple scan configurations. In
      conclusion, the film provides a reliable relative dose measurement method for
      electrons and photons irradiations in the medical field applications. 

PMID- 24880679
TI  - Speech MRI: morphology and function.
AB  - Magnetic Resonance Imaging (MRI) plays an increasing role in the study of speech.
      This article reviews the MRI literature of anatomical imaging, imaging for
      acoustic modelling and dynamic imaging. It describes existing imaging techniques
      attempting to meet the challenges of imaging the upper airway during speech and
      examines the remaining hurdles and future research directions. 

PMID- 24880680
TI  - Chitosan magnetic nanoparticles for pH responsive Bortezomib release in cancer
      therapy.
AB  - The use of nanotechnology in cancer treatment offers exciting opportunities,
      including the possibility of destroying tumors with minimal damage to healthy
      tissue by novel targeted drug delivery systems. pH differences between healthy
      and tumor microenvironment provide pH responsive release of drugs at tumor site
      via smart nanoparticles. In this study, chitosan coated superparamagnetic iron
      oxide nanoparticles (CS MNPs) were in situ synthesized by ionic crosslinking
      method as nanocarrier systems and loaded with the drug Bortezomib (Velcade((r))).
      The drug loading capacity, drug release and stability of CS MNPs were analyzed.
      CS MNPs were visualized inside the cells by fluorescence microscopy. The
      cytotoxicity of Bortezomib, CS MNPs and Bortezomib loaded CS MNPs were tested by
      XTT analyses in vitro. Gene expression analyses revealed that pro-apoptotic PUMA
      and NOXA genes were upregulated while anti-apoptotic BCL-2, SURVIVIN and cIAP-2
      genes were downregulated at Bortezomib loaded CS MNP treated cells.
      Immunocytochemical analyses demonstrated an increase in p53 tumor suppressor
      protein levels at treated cells, which supports the upregulation of PUMA and NOXA
      genes, while Survivin protein level did not significantly change. This study
      points out that the pH responsive magnetic targeting of Bortezomib is more
      efficacious than free drug treatment. Moreover, targeted delivery of Bortezomib
      would reduce the frequency of drug administration by lowering the required amount
      of drug dose. 

PMID- 24880681
TI  - The distribution of heavy metals including Pb, Cd and Cr in Kendari Bay surficial
      sediments.
AB  - The surficial coastal sediments in Kendari Bay are sampled in the field to
      determine the concentration and pollution level of three heavy metals (Pb, Cd and
      Cr). Twenty-five sampling points ranging from the inner (Wanggu River) to the
      outer area of the bay have been chosen. The physicochemical properties, such as
      temperature, pH, salinity and TDS of the overlying water, as well as the sediment
      type and TOC of the surficial sediments, are also measured. The total
      concentrations of the Pb, Cd and Cr in the sediment samples are quantified using
      inductively-coupled plasma mass spectrometry (ICP-MS). The concentrations of the
      heavy metals (Pb, Cd and Cr) ranged from 0.84 to 17.02 MUg/g, 0.02 to 0.17 MUg/g
      and 1.92 to 40.11 MUg/g (dry weight), respectively, following the Cr>Pb>Cd
      sequence. To assess the degree of contamination, a geoaccumulation index (Igeo)
      is measured. Kendari Bay is not a contaminated area regarding Pb, Cd and Cr.

PMID- 24880682
TI  - Coastal surface sediment quality assessment in Leizhou Peninsula (South China
      Sea) based on SEM-AVS analysis.
AB  - Surface sediments from the coastal area of the Leizhou Peninsula in the South
      China Sea were collected and analyzed and the potential ecological risks in the
      area were assessed based on acid-volatile sulfide (AVS) model. The AVS levels are
      between 0.109 and 55.6 MUmol g(-1), with the average at 4.45 MUmol g(-1). The
      high AVS-concentration zones include the aquaculture areas of Liusha Bay and the
      densely populated areas of Zhanjiang Bay. The simultaneously extracted metals
      (SEM) range from 0.026 MUmol g(-1) to 8.61 MUmol g(-1), with the average at 0.843
      MUmol g(-1). Most of high SEM-concentration stations were located in ports or
      aquaculture zones. Most of the coastal surface sediments of the Leizhou Peninsula
      (90%) had no adverse biological effects according to the criterion proposed by
      USEPA (2005); while adverse effects were uncertain in some stations (8%); even in
      2 stations (2%) adverse biological effects may be expected.

PMID- 24880683
TI  - From a millennium base line to 2012: beach litter changes in Wales.
AB  - Forty-five beaches at 41 bathing area locations in Wales were analysed for litter
      in 2000 and 2012, via a standard seven category checklist. Fourteen resorts, 2
      urban, 11 village, 15 rural 3 remote, were graded, A to D. A grade beach numbers
      changed from 5 to19; B, 27 to 24; C, 9 to 2; D, 4 to 0, many beaches maintaining
      their current status. Assuming trend continuance within the next 12 years, the
      A:B grade ratio would approach equilibrium of 44:56, with no grade C or D
      beaches. Recreational litter was ubiquitous; fishing materials prevalent along
      Cardigan Bay. New water treatment plant investment reduced sewage related debris.
      Despite apparent increased awareness of beach litter, improving visitor behaviour
      through information/education should be a future priority. Removing a few gross
      items could improve beach grades at little cost to local authorities and benefits
      to the Welsh economy.

PMID- 24880684
TI  - Dominance of clonal complex 10 among the levofloxacin-resistant Streptococcus
      agalactiae isolated from bacteremic patients in a Korean hospital.
AB  - Streptococcus agalactiae has emerged as an important cause of invasive infection
      in adults. Forty-nine S. agalactiae isolates (41 from adults and 8 from neonates)
      were collected during a 4-year period (2010-2013) and analyzed by multilocus
      sequence typing (MLST). Antibiotic susceptibility to erythromycin, clindamycin
      and levofloxacin was determined and the determinants of resistance (ermA, ermB,
      ermC, mefA, lnuB) were detected by PCR and mutation in gyrA, gyrB, parC and parE
      gene was investigated by sequence analysis. They were resolved into 14 sequence
      types (STs) and belonged to five clonal complexes (CCs). The distribution of CC
      was significantly different according to the age group; CC1 (18/41) and CC10
      (13/41) was the most common among the adult isolates but CC19 (5/8) was
      predominant among the neonatal isolates. The resistance rate to erythromycin,
      clindamycin was 18.4% and 24.5%, respectively. Among the 13 strains resistant to
      erythromycin and/or clindamycin, two isolates harbored ermA and 10 isolates
      harbored ermB. The levofloxacin resistance rate was very high (32.7%) and was
      significantly higher in CC10 (71.4%). All the levofloxacin-resistant isolates had
      identical gyrA substitution (Ser81Leu) but parC substitution was different
      according to the CCs. The additional mutation in parE (His221Tyr) was found only
      in CC19. Continuous monitoring of the fluoroquinolone resistance and genotypic
      distribution among S. agalactiae is needed.

PMID- 24880685
TI  - SiO2@Au nanoshells-based SERS method for detection of sunset yellow and
      chrysoidine.
AB  - A novel surface-enhanced Raman scattering (SERS) substrate made up of SiO2@Au
      nanoshells has been developed for detecting sunset yellow and chrysoidine. It
      exhibits an excellent enrichment SERS effect on these two colorant molecules. In
      this work, density functional theory (DFT) calculations have been carried out to
      determine the molecular structure and theoretical Raman spectra. This provided a
      good description of the characteristic peaks of the molecules. In addition, the
      appropriate thicknesses of the shell and environment pH have been derived to
      obtain improved SERS signals. The lowest concentration is 1 ppm and 0.5 ppm for
      sunset yellow and chrysoidine, respectively. Under optimal detection condition,
      it has proved possible to distinguish each colorant by its characteristic peaks
      in the SERS spectra of a mixture of the two colorants.

PMID- 24880686
TI  - EuGene-PP: a next-generation automated annotation pipeline for prokaryotic
      genomes.
AB  - It is now easy and increasingly usual to produce oriented RNA-Seq data as a
      prokaryotic genome is being sequenced. However, this information is usually just
      used for expression quantification. EuGene-PP is a fully automated pipeline for
      structural annotation of prokaryotic genomes integrating protein similarities,
      statistical information and any oriented expression information (RNA-Seq or
      tiling arrays) through a variety of file formats to produce a qualitatively
      enriched annotation including coding regions but also (possibly antisense) non
      coding genes and transcription start sites. AVAILABILITY AND IMPLEMENTATION:
      EuGene-PP is an open-source software based on EuGene-P integrating a Galaxy
      configuration. EuGene-PP can be downloaded at eugene.toulouse.inra.fr.

PMID- 24880687
TI  - Structures of HIV-1 RT-RNA/DNA ternary complexes with dATP and nevirapine reveal
      conformational flexibility of RNA/DNA: insights into requirements for RNase H
      cleavage.
AB  - In synthesizing a double-stranded DNA from viral RNA, HIV-1 reverse transcriptase
      (RT) generates an RNA/DNA intermediate. RT also degrades the RNA strand and
      synthesizes the second DNA strand. The RNase H active site of RT functions as a
      nuclease to cleave the RNA strand; however, the structural basis for
      endonucleolytic cleavage of the RNA strand remains elusive. Here we report
      crystal structures of RT-RNA/DNA-dATP and RT-RNA/DNA-nevirapine (NVP) ternary
      complexes at 2.5 and 2.9 A resolution, respectively. The polymerase region of RT
      RNA/DNA-dATP complex resembles DNA/DNA ternary complexes apart from additional
      interactions of 2'-OH groups of the RNA strand. The conformation and binding of
      RNA/DNA deviates significantly after the seventh nucleotide versus a DNA/DNA
      substrate. Binding of NVP slides the RNA/DNA non-uniformly over RT, and the RNA
      strand moves closer to the RNase H active site. Two additional structures, one
      containing a gapped RNA and another a bulged RNA, reveal that conformational
      changes of an RNA/DNA and increased interactions with the RNase H domain,
      including the interaction of a 2'-OH with N474, help to position the RNA nearer
      to the active site. The structures and existing biochemical data suggest a
      nucleic acid conformation-induced mechanism for guiding cleavage of the RNA
      strand. 

PMID- 24880688
TI  - A highly processive topoisomerase I: studies at the single-molecule level.
AB  - Amongst enzymes which relieve torsional strain and maintain chromosome
      supercoiling, type IA topoisomerases share a strand-passage mechanism that
      involves transient nicking and re-joining of a single deoxyribonucleic acid (DNA)
      strand. In contrast to many bacterial species that possess two type IA
      topoisomerases (TopA and TopB), Actinobacteria possess only TopA, and unlike its
      homologues this topoisomerase has a unique C-terminal domain that lacks the Zn
      finger motifs characteristic of type IA enzymes. To better understand how this
      unique C-terminal domain affects the enzyme's activity, we have examined DNA
      relaxation by actinobacterial TopA from Streptomyces coelicolor (ScTopA) using
      real-time single-molecule experiments. These studies reveal extremely high
      processivity of ScTopA not described previously for any other topoisomerase of
      type I. Moreover, we also demonstrate that enzyme processivity varies in a torque
      dependent manner. Based on the analysis of the C-terminally truncated ScTopA
      mutants, we propose that high processivity of the enzyme is associated with the
      presence of a stretch of positively charged amino acids in its C-terminal region.

PMID- 24880689
TI  - GPS-SUMO: a tool for the prediction of sumoylation sites and SUMO-interaction
      motifs.
AB  - Small ubiquitin-like modifiers (SUMOs) regulate a variety of cellular processes
      through two distinct mechanisms, including covalent sumoylation and non-covalent
      SUMO interaction. The complexity of SUMO regulations has greatly hampered the
      large-scale identification of SUMO substrates or interaction partners on a
      proteome-wide level. In this work, we developed a new tool called GPS-SUMO for
      the prediction of both sumoylation sites and SUMO-interaction motifs (SIMs) in
      proteins. To obtain an accurate performance, a new generation group-based
      prediction system (GPS) algorithm integrated with Particle Swarm Optimization
      approach was applied. By critical evaluation and comparison, GPS-SUMO was
      demonstrated to be substantially superior against other existing tools and
      methods. With the help of GPS-SUMO, it is now possible to further investigate the
      relationship between sumoylation and SUMO interaction processes. A web service of
      GPS-SUMO was implemented in PHP+JavaScript and freely available at
      http://sumosp.biocuckoo.org.

PMID- 24880690
TI  - A SET-domain-independent role of WRAD complex in cell-cycle regulatory function
      of mixed lineage leukemia.
AB  - MLL, the trithorax ortholog, is a well-characterized histone 3 lysine 4
      methyltransferase that is crucial for proper regulation of the Hox genes during
      embryonic development. Chromosomal translocations, disrupting the Mll gene, lead
      to aggressive leukemia with poor prognosis. However, the functions of MLL in
      cellular processes like cell-cycle regulation are not well studied. Here we show
      that the MLL has a regulatory role during multiple phases of the cell cycle. RNAi
      mediated knockdown reveals that MLL regulates S-phase progression and, proper
      segregation and cytokinesis during M phase. Using deletions and mutations, we
      narrow the cell-cycle regulatory role to the C subunit of MLL. Our analysis
      reveals that the transactivation domain and not the SET domain is important for
      the S-phase function of MLL. Surprisingly, disruption of MLL-WRAD interaction is
      sufficient to disrupt proper mitotic progression. These mitotic functions of WRAD
      are independent of SET domain of MLL and, therefore, define a new role of WRAD in
      subset of MLL functions. Finally, we address the overlapping and unique roles of
      the different SET family members in the cell cycle. 

PMID- 24880691
TI  - Strand exchange of telomeric DNA catalyzed by the Werner syndrome protein (WRN)
      is specifically stimulated by TRF2.
AB  - Werner syndrome (WS), caused by loss of function of the RecQ helicase WRN, is a
      hereditary disease characterized by premature aging and elevated cancer
      incidence. WRN has DNA binding, exonuclease, ATPase, helicase and strand
      annealing activities, suggesting possible roles in recombination-related
      processes. Evidence indicates that WRN deficiency causes telomeric abnormalities
      that likely underlie early onset of aging phenotypes in WS. Furthermore, TRF2, a
      protein essential for telomere protection, interacts with WRN and influences its
      basic helicase and exonuclease activities. However, these studies provided little
      insight into WRN's specific function at telomeres. Here, we explored the
      possibility that WRN and TRF2 cooperate during telomeric recombination processes.
      Our results indicate that TRF2, through its interactions with both WRN and
      telomeric DNA, stimulates WRN-mediated strand exchange specifically between
      telomeric substrates; TRF2's basic domain is particularly important for this
      stimulation. Although TRF1 binds telomeric DNA with similar affinity, it has
      minimal effects on WRN-mediated strand exchange of telomeric DNA. Moreover, TRF2
      is displaced from telomeric DNA by WRN, independent of its ATPase and helicase
      activities. Together, these results suggest that TRF2 and WRN act coordinately
      during telomeric recombination processes, consistent with certain telomeric
      abnormalities associated with alteration of WRN function. 

PMID- 24880693
TI  - Predicting dyscontrolled drinking with implicit and explicit measures of alcohol
      attitude.
AB  - BACKGROUND: A defining feature of alcohol addiction is dyscontrol - drinking
      despite intentions to restrain use. Given that dyscontrolled drinking involves an
      automatic (nonvolitional) element and that implicit measures are designed to
      assess automatic processes, it follows that implicit measures may be particularly
      useful for predicting dyscontrolled alcohol use. Although there is accumulating
      evidence for the benefit of using implicit measures to predict nonvolitional
      behaviors, relatively little research has examined such predictive validity for
      alcohol dyscontrol. The current study was designed to examine whether an implicit
      measure of alcohol attitude would predict variance of dyscontrol above that
      explained by typical drinking behavior and an explicit measure of alcohol
      attitude. METHODS: A sample of 62 undergraduate students completed implicit and
      explicit measures of alcohol-positive (relative to alcohol-negative) valence
      associations and retrospective self-report measures of typical drinking behavior
      and difficulty in controlling alcohol consumption. RESULTS: Both the implicit and
      explicit measures predicted alcohol dyscontrol. The implicit measure continued to
      predict dyscontrol when controlling for the explicit measure and typical drinking
      behavior. CONCLUSIONS: These findings indicate that assessing the automaticity of
      alcohol-positive associations may be beneficial for predicting clinically
      relevant behaviors such as post-treatment outcome.

PMID- 24880692
TI  - The association between cue-reactivity in the precuneus and level of dependence
      on nicotine and alcohol.
AB  - BACKGROUND: Given numerous reports implicating involvement of the precuneus in
      cue-reactivity paradigms, the goal of this investigation was to examine the
      relationship between activation of the precuneus in response to drug cues and
      measures of subjective craving and severity of dependence in volunteers who were
      comorbid for alcohol and nicotine abuse. METHODS: Forty research participants,
      who all reported heavy drinking and daily smoking, were recruited (15 women; 70%
      Caucasian; mean age=31.2 years) for a functional magnetic resonance imaging
      (fMRI) session involving a cigarette video-cues task and an alcohol taste-cues
      task. Mean precuneus activation from both tasks during cue presentation was
      subjected to bivariate correlation analyses with indices of dependence severity
      and subjective craving. RESULTS: Precuneus activation in the contrast of
      Cigarette Cues vs. Control Cues was positively correlated with scores on the
      Fagerstrom Test of Nicotine Dependence (r=0.389, p=0.016), and activation in the
      Alcohol Cues vs. Control Cues contrast was positively correlated with Alcohol
      Dependence Scale scores (r=0.338, p=0.038). No correlations with subjective
      craving were observed (ps>0.05). CONCLUSIONS: These findings indicate that the
      precuneus is involved in cue reactivity for both cigarettes and alcohol, and that
      this involvement is moderated by severity of drug dependence. The precuneus may
      be a cortical locus for neuroplastic changes related to drug dependence.

PMID- 24880695
TI  - The effect of a nurse team leader on communication and leadership in major trauma
      resuscitations.
AB  - BACKGROUND: Effective assessment and resuscitation of trauma patients requires an
      organised, multidisciplinary team. Literature evaluating leadership roles of
      nurses in trauma resuscitation and their effect on team performance is scarce.
      AIM: To assess the effect of allocating the most senior nurse as team leader of
      trauma patient assessment and resuscitation on communication, documentation and
      perceptions of leadership within an Australian emergency department. METHODS: The
      study design was a pre-post-test survey of emergency nursing staff (working at
      resuscitation room level) perceptions of leadership, communication, and
      documentation before and after the implementation of a nurse leader role. Patient
      records were audited focussing on initial resuscitation assessment, treatment,
      and nursing clinical entry. Descriptive statistical analyses were performed.
      RESULTS: Communication trended towards improvement. All (100%) respondents post
      test stated they had a good to excellent understanding of their role, compared to
      93.2% pre-study. A decrease (58.1-12.5%) in 'intimidating personality' as a
      negative aspect of communication. Nursing leadership had a 6.7% increase in the
      proportion of those who reported nursing leadership to be good to excellent.
      Accuracy of clinical documentation improved (P = 0.025). CONCLUSION: Trauma nurse
      team leaders improve some aspects of communication and leadership. Development of
      trauma nurse leaders should be encouraged within trauma team training programmes.

PMID- 24880694
TI  - The Flash Environmental Assessment Tool: worldwide first aid for chemical
      accidents response, pro action, prevention and preparedness.
AB  - The United Nations response mechanism to environmental emergencies requested a
      tool to support disaster assessment and coordination actions by United Nations
      Disaster Assessment and Coordination (UNDAC) teams. The tool should support on
      site decision making when substantial chemical emissions affect human health
      directly or via the environment and should be suitable for prioritizing impact
      reduction management options under challenging conditions worldwide. To answer
      this need, the Flash Environmental Assessment Tool (FEAT) was developed and the
      scientific and practical underpinning and application of this tool are described
      in this paper. FEAT consists of a printed decision framework and lookup tables,
      generated by combining the scientific data on chemicals, exposure pathways and
      vulnerabilities with the pragmatic needs of emergency field teams. Application of
      the tool yields information that can help prioritize impact reduction measures.
      The first years of use illustrated the usefulness of the tool as well as
      suggesting additional uses and improvements. An additional use is application of
      the back-office tool (Hazard Identification Tool, HIT), the results of which aid
      decision-making by the authorities of affected countries and the preparation of
      field teams for on-site deployment. Another extra use is in disaster pro action
      and prevention. In this case, the application of the tool supports safe land-use
      planning and improved technical design of chemical facilities. UNDAC teams are
      trained to use the tool after large-scale sudden onset natural disasters. 

PMID- 24880696
TI  - Postoperative delirium and pre-fracture disability predict 6-month mortality
      among the oldest old hip fracture patients.
AB  - BACKGROUND: Age is one of the most robust risk factors for hip fracture. Recent
      projections indicate that almost half of hip fractures are occurring with an
      increasing trend among the "oldest old" (i.e., in those aged >85 years). AIMS: To
      compare clinical characteristics, outcomes, and risk factors for 6-month
      mortality in two groups of "oldest old" patients (group 1 = 85-89, group 2 > 90
      years), after hip fracture surgery. METHODS: Observational prospective cohort
      study with 6-month follow-up, performed in an Orthogeriatric Unit of an academic
      hospital between March 2007 and November 2012. RESULTS: Two hundred seventy-five
      patients (group 1: N = 171; group 2: N = 104) underwent a comprehensive geriatric
      assessment, including demographics, clinical, functional, nutritional, and mental
      status. The 6-month rehospitalization and mortality rates after surgery were
      assessed through structured telephone interviews with patient's caregivers.
      Multivariate logistic regression models were used to evaluate predictors of 6
      month mortality, adjusting for relevant covariates. Fifty-eight patients died at
      follow-up. The in-hospital and 6-month mortality rates were significantly higher
      for patients of group 2 than for those of group 1. After adjusting for
      covariates, the multivariate logistic regressions showed that severe disability
      (OR 2.24, 95 % CI 1.08-4.65) and postoperative delirium (POD) (OR 3.80, 95 % CI
      1.72-8.39) were predictors of 6-month mortality. CONCLUSIONS: Patients aged >90
      years who underwent hip fracture surgery are more likely to die at 6 months than
      those aged 85-89 years. Pre-fracture disability and POD are predictors of this
      excess of mortality.

PMID- 24880697
TI  - Psychological effects of treatment with new oral anticoagulants in elderly
      patients with atrial fibrillation: a preliminary report.
AB  - BACKGROUND AND AIMS: Atrial fibrillation (AF) is the most common arrhythmia in
      elderly people, yet oral anticoagulation is underused in the aged. We tried to
      determine whether new oral anticoagulants (NOA) have greater psychological
      tolerability than warfarin. METHODS: Age-, gender-matched groups of AF patients
      receiving NOA (N = 15) or warfarin (N = 15) were assessed with the Anti-Clot
      Treatment Scale (ACTS) and the Perceived Stress Scale (PSS). RESULTS: Patients
      were old (81 +/- 9 years). NOA group showed greater psychological satisfaction,
      with lower therapy-related burden (ACTS burdens: 16.3 +/- 4.5 vs. 32.9 +/- 10.2,
      p < 0.001) and higher awareness of benefits (ACTS benefits: 13.0 +/- 1.3 vs. 10.8
      +/- 1.9, p = 0.001). Even stress was lower (PSS: 13.1 +/- 4.0 vs. 17.1 +/- 4.2, p
      = 0.013). The multivariate analysis confirmed these findings, showing that higher
      levels of anxiety and depression could justify more stress in warfarin patients.
      CONCLUSIONS: The results of this preliminary study show that NOA have an improved
      psychological impact compared with warfarin in elderly patients.

PMID- 24880698
TI  - The physiological characteristics of community-dwelling elderly Japanese with
      airflow limitation: a cross-sectional study.
AB  - BACKGROUND AND AIMS: The aim of this study was to investigate the physiological
      characteristics of community-dwelling elderly subjects, aged >=65 years, with
      airflow limitation in the Japanese community. METHODS: Subjects were recruited
      through local press advertisement, and 180 individuals were enrolled. Data on
      age, body mass index (BMI), gender, smoking history, and past medical history
      were obtained, as were pulmonary function parameters, skeletal muscle mass index,
      and physical activity. RESULTS: The final study population comprised 161
      participants from whom we obtained valid spirometry results. The mean age of this
      population was 73.4 +/- 4.4 years, and 78 participants (48.4 %) were men. The
      prevalence of airflow limitation was 29.2 % (n = 47). Subjects with airflow
      limitation were significantly older (P = 0.01) and had poorer pulmonary function
      (P < 0.01), lower BMI (P < 0.01), and lower skeletal muscle mass index (P = 0.03)
      than healthy elderly subjects. Furthermore, skeletal muscle mass index was
      significantly correlated with the percentage of predicted forced vital capacity
      (r = 0.45, P < 0.05) and forced expiratory volume in 1 s (r = 0.50, P < 0.05)
      only in men with airflow limitation. CONCLUSIONS: We found that the skeletal
      muscle mass index was significantly reduced in community-dwelling elderly with
      airflow limitation, and the skeletal muscle mass index was correlated with
      pulmonary function only in men with airflow limitation.

PMID- 24880700
TI  - Longitudinal association between BMI at diagnosis and HIV disease progression.
AB  - Increased body mass index (BMI) has been associated with adverse health outcomes
      but the effect of BMI on HIV immune markers over time post-HAART is not clearly
      established. Data were abstracted from 396 medical records at the Ryan White
      Clinic in South Carolina. All HIV-infected adults who were >=18 years of age,
      diagnosed between 1997 and 2010, had weight and height measured within 3 months
      of diagnosis and had at least one follow-up visit within 6 months of diagnosis,
      were eligible. The mean CD4 count was calculated for each BMI category and mixed
      regression analyses was used to determine the association between BMI and CD4
      count over time. The overall mean BMI was 27.4 kg/m(2). Longitudinally, the mean
      CD4 count was 611.2 cells/mm(3) for obese individuals, 598.1 cells/mm(3) for
      overweight individuals and 550.5 cells/mm(3) for normal weight individuals. When
      compared to the normal weight category, the obese category had significantly
      larger increases in CD4 count (5.5 cells/mm(3), P < 0.001) versus the overweight
      category (-2.1 cells/mm(3), P < 0.001). HIV-infected individuals who were obese
      at diagnosis had larger increases in CD4 counts over time when compared to
      overweight individuals at diagnosis. This suggests that providers should pay
      closer attention to weight at diagnosis to predict the response to treatment and
      disease trajectory. 

PMID- 24880699
TI  - Modeling life satisfaction in spinal cord injury: the role of psychological
      resources.
AB  - PURPOSE: The aims of the study were (1) to examine the associations between the
      psychological resources general self-efficacy (GSE) and purpose in life (PIL),
      appraisals, coping and life satisfaction, and (2) to examine whether the effects
      of the psychological resources on life satisfaction are mediated by appraisals
      and coping, as proposed by the spinal cord injury adjustment model (SCIAM).
      METHODS: Cross-sectional multicenter study conducted with persons with spinal
      cord injury (SCI) living in the community in Switzerland (N = 516). Pearson's
      correlations were calculated for aim 1, and structural equation modeling was
      conducted to address aim 2. RESULTS: GSE (r = .48) and PIL (r = .58) were
      positively related to life satisfaction. The initial model corresponding to the
      SCIAM yielded a poor model fit. The final model had a good model fit [chi (2) =
      66.0, df = 21, p < .01, RMSEA = .065 (90 % confidence interval .048-.082), CFI =
      .97] explaining 57 % of variance of life satisfaction. PIL had a direct large
      effect on life satisfaction (beta = .54). The influence of GSE on life
      satisfaction was mediated by loss appraisals. Avoidance, active and humor coping
      had small effects on life satisfaction. CONCLUSIONS: Psychological resources have
      a substantial effect on life satisfaction in persons with SCI. Our results
      correspond with the SCIAM and its conceptualization of adjustment as a
      multifactorial process, but did not fully support the hypothesized mediation. PIL
      was strongly related to higher life satisfaction and may be a suitable
      intervention target to support persons with SCI.

PMID- 24880701
TI  - Immunogenicity of an inactivated Chinese bovine viral diarrhea virus 1a (BVDV 1a)
      vaccine cross protects from BVDV 1b infection in young calves.
AB  - Bovine viral diarrhea virus (BVDV) 1a and 1b strains are the predominant
      subgenotypes in China. Because of the genetic and antigenic variability among
      different BVDV strains, a vaccine effective in one region may fail to protect
      against infections caused by different virus strains in another region. No BVDV
      vaccine developed with the predominant strains in China are available. In this
      study, the immunogenicity of an inactivated Chinese BVDV 1a NM01 vaccine strain
      was evaluated by challenging with a Chinese BVDV 1b JL strain. Ten 2-4-month-old
      calves were intramuscularly vaccinated with a single dose of the vaccine strain
      and boosted with same dose three weeks after the first vaccination, with five
      mock immunized calves serving as a control group. The average titer of
      neutralization antibody to BVDV 1a and BVDV 1b of immunized calves reached 1:410
      and 1:96, respectively, at 21 days post the second vaccination. Twenty-one days
      post the second vaccination, all calves were challenged with strain JL. The
      clinical signs, such as the temperature and leukopenia of the immunized calves
      and viral shedding, were significantly less than the mock immunized calves after
      challenging with the virulent BVDV 1b strain, indicating that the BVDV 1a vaccine
      strain elicited efficacious protection against the endemic BVDV 1b strain in
      China. To the best of our knowledge, this is the first report of an inactivated
      BVDV vaccine which demonstrated effective cross-protection against BVDV type 1b
      infection in China. 

PMID- 24880702
TI  - Evaluation of avian paramyxovirus serotypes 2 to 10 as vaccine vectors in
      chickens previously immunized against Newcastle disease virus.
AB  - Newcastle disease virus (NDV), also known as avian paramyxovirus (APMV) serotype
      1, is used as a vaccine vector to express the hemagglutinin protein of avian
      influenza (AI) virus. However, use of live NDV recombinant vaccines expressing AI
      virus hemagglutinin is not desirable in emergency vaccination programs to control
      severe AI outbreaks in chickens, because commercial chickens often possess pre
      existing NDV immunity induced by routine vaccination. Therefore, a novel vaccine
      vector is required for emergency vaccination of chickens to control AI during
      outbreaks. We investigated whether candidate APMV strains could be used as
      vaccine vectors that could evade the pre-existing immunity acquired by chickens
      through NDV vaccination and that would replicate in the mucosal tissues where AI
      virus primarily replicates. To this end, we examined strains of APMV serotypes 2
      to 10 for their immunogenicity and replication in chickens with pre-existing
      immunity to NDV. APMV serotypes 2, 6, and 10 were the least cross-reactive to
      antibodies to NDV in hemagglutination inhibition and/or virus neutralization
      tests. Virus replication in mucosal tissues, as well as antibody response after
      oculonasal inoculation, was observed when 7-week-old chickens were challenged
      with APMV of serotype 2, 6, or 10. The APMV also replicated in mucosal tissues
      and induced antibody responses in chickens that had been vaccinated twice with
      NDV before challenge. These results warrant further study to develop vaccine
      vectors based on APMV serotype 2, 6, or 10 for emergency vaccination of chickens
      against AI. 

PMID- 24880703
TI  - Class B CpG ODN stimulation upregulates expression of TLR21 and IFN-gamma in
      chicken Harderian gland cells.
AB  - This study aimed to evaluate the response of Harderian gland (HG) cells after in
      vitro stimulation with class B synthetic oligodeoxyribonucleotides (ODN)
      containing CpG motifs. This knowledge is of importance for the development of
      mucosal vaccines for poultry, such as eye-drop or spray vaccines, to determine if
      class B CpG ODN can act as an vaccine adjuvant or as a prophylactic treatment
      mainly against respiratory disease viruses. The relative expression of Toll-like
      receptor 21 (TLR21), interferon (IFN)-gamma, interleukin (IL)-1beta and IL-10
      genes were quantified at 1, 3, 6 and 18 h post-stimulation of HG cells from 5
      week-old birds. In addition, it was also investigated if expression of these
      genes was affected by the age of the birds (differences between 5- and 12-week
      old birds), concentrations of ODN or cell preparation method used. Class B CpG
      ODN induced upregulation of TLR21 and IFN-gamma mRNA expression levels at 1h post
      stimulation depending on concentration of ODN used but only in HG cells isolated
      from young birds.

PMID- 24880704
TI  - You are what you eat: fatty acid profiles as a method to track the habitat
      movement of an insect.
AB  - Tracking the movement of small organisms is of tremendous importance to
      understanding the ecology of populations, communities, and ecosystems. However,
      it remains one of the most difficult challenges facing the field of movement
      ecology. We developed an intrinsic marking technique for tracking small organisms
      using dietary fatty acid profiles as a biomarker as well as for clarifying source
      sink dynamics between populations on a landscape level. Navel orangeworm moths
      (NOW), Amyelois transitella (Walker) (Lepidoptera: Pyralidae), raised on two
      different host plants with significantly different fatty acid profiles, were used
      to develop a model that distinguishes NOW based on their larval host plant. Wild
      NOW from both known and unknown host plants were used to validate the model. NOW
      fatty acid profiles showed striking similarities to the fatty acid profile of
      their host plant demonstrating that fatty acids can act as an intrinsic marking
      technique for quantifying the movement of small organisms. We anticipate that
      given sufficient spatial variation in dietary fatty acids, this technique will be
      useful in studying the movement of arthropods and other invertebrates
      particularly when addressing questions of source-sink dynamics. 

PMID- 24880705
TI  - A multicenter study of cross-priming amplification for tuberculosis diagnosis at
      peripheral level in China.
AB  - Cross-Priming Amplification (CPA) has been shown to rapidly and effectively
      detect Mycobacterium tuberculosis (MTB) in sputum samples under isothermal
      conditions. However, no performance data exist from peripheral-level tuberculosis
      (TB) clinics in tuberculosis-endemic countries. We conducted a clinical trial at
      four county-level TB clinics in China to evaluate the effectiveness of the CPA
      assay. TB suspects were continuously enrolled by a clinician at each clinic.
      Following informed consent, each patient provided two sputum specimens (spot and
      morning sputum). Sputum samples were tested by smear microscopy, solid culture
      and CPA. The National TB reference laboratory (NTRL) collected all culture
      positive strains and performed 16S-23S rDNA internal transcribed spacer (ITS)
      sequence analysis for strain identification. Solid culture was used as the gold
      standard to evaluate the effectiveness of CPA in detecting MTB. A total of 2200
      TB-suspected patients were enrolled at the four county-level TB clinics. Compared
      to solid culture, the sensitivity and specificity of the CPA test for MTB
      detection within this group was 84.1% (95%CI, 79.5-88.6) and 97.8% (95%CI, 97.1
      98.5), respectively, and the sensitivity in smear-negative cases was 59.8%
      (95%CI, 49.8-69.8). The test failure rate of CPA was 0.8% (32/3918),
      significantly lower than the 1.7% (106/6138) culture contamination rate.

PMID- 24880706
TI  - Protective efficacy of piperine against Mycobacterium tuberculosis.
AB  - Piperine a trans-trans isomer of 1-piperoyl-piperidine was evaluated for its
      immunomodulatory activity to enhance the efficacy of rifampicin in a murine model
      of Mycobacterium tuberculosis infection. In-vitro immunomodulation of piperine
      was tested on mouse splenocytes for lymphocyte proliferation, cytokine production
      and macrophage activation. Protective efficacy of piperine was tested in a mice
      infection model of M. tuberculosis for the activation of Th-1 response and
      synergistic combination efficacy with rifampicin. Murine splenocytes exposed to
      piperine exhibited proliferation of T and B cell, increased Th-1 cytokines and
      enhanced macrophage activation. Piperine (1 mg/kg) in mice infected with M.
      tuberculosis activated the differentiation of T cells into Th-1 sub-population
      (CD4+ / CD8+ subsets). There was an increase in secretion of Th-1 cytokines (IFN
      gamma and IL-2) by these cells. The qRT-PCR studies revealed corresponding
      increases in the mRNA transcripts of IFN-gamma and IL-2 in the infected lung
      tissues. Combination of piperine and rifampicin (1 mg/kg) exhibited better
      efficacy of and resulted in additional 1.4 to 0.8 log reduction in lung cfu as
      compared to rifampicin alone. The up-regulation of Th1 immunity by piperine can
      be synergistically combined with rifampicin to improve its therapeutic efficacy
      in immune-compromised TB patients.

PMID- 24880707
TI  - Mechanisms of skeletal muscle ageing; avenues for therapeutic intervention.
AB  - Age-related loss of muscle mass and function, termed sarcopenia, is a
      catastrophic process, which impacts severely on quality of life of older people.
      The mechanisms underlying sarcopenia are unclear and the development of optimal
      therapeutic interventions remains elusive. Impaired regenerative capacity,
      attenuated ability to respond to stress, elevated reactive oxygen species
      production and low-grade systemic inflammation are all key contributors to
      sarcopenia. Pharmacological intervention using compounds such as 17AAG, SS-31 and
      Bimagrumab or naturally occurring polyphenols to target specific pathways show
      potential benefit to combat sarcopenia although further research is required,
      particularly to identify the mechanisms by which muscle fibres are completely
      lost with increasing age. 

PMID- 24880708
TI  - Targeting P2 receptors--current progress in treating musculoskeletal diseases.
AB  - It is widely recognized that purinergic signalling, extracellular nucleotides
      acting at purinergic receptors, is the most primitive and ubiquitous signalling
      system participating in numerous biological processes in almost all tissue types.
      The P2 receptors, including P2X and P2Y purinoceptor subtypes, have been proposed
      to play important roles in the musculoskeletal systems since the early 1990s.
      During the past five years, significant progress in this field has been made;
      this review will summarize these most recent developments and highlight the
      pharmaceutical potential from these findings. 

PMID- 24880709
TI  - Human genome variability, natural selection and infectious diseases.
AB  - The recent availability of large-scale sequencing DNA data allowed researchers to
      investigate how genomic variation is distributed among populations. While
      demographic factors explain genome-wide population genetic diversity levels,
      scans for signatures of natural selection pinpointed several regions under non
      neutral evolution. Recent studies found an enrichment of immune-related genes
      subjected to natural selection, suggesting that pathogens and infectious diseases
      have imposed a strong selective pressure throughout human history. Pathogen
      mediated selection often targeted regulatory sites of genes belonging to the same
      biological pathway. Results from these studies have the potential to identify
      mutations that modulate infection susceptibility by integrating a population
      genomic approach with molecular immunology data and large-scale functional
      annotations. 

PMID- 24880710
TI  - Assessment of regression in successive primary melanomas.
AB  - INTRODUCTION AND OBJECTIVES: It has been suggested that patients who have had a
      melanoma may develop increased immunity against certain antigens expressed by
      tumor-associated melanocytes. Thus our objective was to review the records of
      patients with successive primary melanomas to ascertain whether the pattern of
      regression might indicate the presence of an immunization effect arising from the
      first melanoma. MATERIAL AND METHODS: A review of all the cases recorded in the
      melanoma database of our dermatology department between 2000 and 2012 identified
      19 patients who had multiple asynchronous melanomas (2.56% of all the cases
      recorded). We studied the presence or absence of regression in these melanomas
      and other clinical and histological characteristics. RESULTS: The presence of
      regression was significantly higher in successive melanomas than in the first
      tumors identified (42.10% vs 21.05%, P=.018). Regression of at least 1 melanoma
      was observed in 42.10% of the patients studied and regression of 2 melanomas was
      observed in 21.05%. In no case was regression observed in the first melanoma and
      not in the second; however, in 21.05% of the patients there was evidence of
      regression in the second tumor and none in the first. CONCLUSIONS: Our findings
      suggest the possibility that the first melanoma produces an immunization effect
      in some patients who develop multiple asynchronous melanomas.

PMID- 24880711
TI  - Vulvovaginal angiomyofibroblastomas: morphologic, immunohistochemical, and
      fluorescence in situ hybridization analysis for deletion of 13q14 region.
AB  - Angiomyofibroblastoma (AMFB) is a benign tumor that belongs to the category of
      the "stromal tumors of the lower female genital tract," together with cellular
      angiofibroma and myofibroblastoma. Previous studies have shown overlapping
      morphologic and immunohistochemical features between these tumors and spindle
      cell lipoma, mammary-type myofibroblastoma, and vulvovaginal cellular
      angiofibroma and myofibroblastoma. In addition, typical loss of genetic material
      from the 13q14 region has been documented in all the above-mentioned tumors,
      suggesting that they are histogenetically related. We report the
      clinicopathologic features of 11 new cases of vulvovaginal AMFBs. Histologically,
      the basic common theme was a proliferation of bland-looking spindle to round-to
      epithelioid cells set in an edematous to fibrous stroma, frequently arranged
      around thin-walled blood vessels. Two cases were composed of a prominent mature
      fatty component closely admixed with typical areas of AMFB, and thus, they were
      designated as "lipomatous AMFBs." Notably, 1 case was closely reminiscent of
      Sertoli cell tumor, sclerosing type, because of its predominant cord-like
      arrangement. Immunohistochemically, all tumors were diffusely positive for
      vimentin, whereas desmin and alpha-smooth muscle actin were expressed in a
      minority of cases, suggesting a fibroblastic rather than myofibroblastic
      differentiation. Most cases of AMFBs coexpressed Bcl-2 protein and CD99.
      Interestingly, all 5 cases of AMFB with evaluable signals failed to show
      monoallelic loss of FOXO1 loci (13q14) by fluorescence in situ hybridization.
      These cytogenetic findings suggest that vulvovaginal AMFB is not genetically
      related to cellular angiofibroma and myofibroblastoma of the lower female genital
      tract. 

PMID- 24880712
TI  - Ultrastructural characterization and multilocus sequence analysis (MLSA) of
      'Candidatus Rickettsiella isopodorum', a new lineage of intracellular bacteria
      infecting woodlice (Crustacea: Isopoda).
AB  - The taxonomic genus Rickettsiella (Gammaproteobacteria; Legionellales) comprises
      intracellular bacteria associated with a wide range of arthropods including
      insects, arachnids and crustaceans. The present study provides ultrastructural
      together with genetic evidence for a Rickettsiella bacterium in the common rough
      woodlouse, Porcellio scaber (Isopoda, Porcellionidae), occurring in Germany, and
      shows that this bacterium is very closely related to one of the same genus
      occurring in California that infects the pill bug, Armadillidium vulgare
      (Isopoda, Armadillidiidae). Both bacterial isolates displayed the ultrastructural
      features described previously for crustacean-associated bacteria of the genus
      Rickettsiella, including the absence of well-defined associated protein crystals;
      occurrence of the latter is a typical characteristic of infection by this type of
      bacteria in insects, but has not been reported in crustaceans. A molecular
      systematic approach combining multilocus sequence analysis (MLSA) with likelihood
      based significance testing demonstrated that despite their distant geographic
      origins, both bacteria form a tight sub-clade within the genus Rickettsiella. In
      the 16S rRNA gene trees, this sub-clade includes other bacterial sequences from
      woodlice. Moreover, the bacterial specimens from P. scaber and A. vulgare are
      found genetically or morphologically different from each of the four currently
      recognized Rickettsiella species. Therefore, the designation 'Candidatus
      Rickettsiella isopodorum' is introduced for this new lineage of isopod-associated
      Rickettsiella bacteria.

PMID- 24880713
TI  - MRI diagnosis of muscle denervation from herpes zoster with discordant
      distribution of the skin rash.
AB  - Herpes zoster is a common disorder characterized by a painful rash along a
      dermatome caused by reactivation of the varicella zoster virus (VZV). Muscle
      denervation injury from motor involvement is an uncommon phenomenon. Discordant
      distribution of the skin rash and motor nerve involvement, presenting as a skin
      rash in one body part and muscle weakness or pain from nerve involvement in
      another body part is an even more uncommonly reported finding. We present an
      unusual case of muscle denervation injury resulting from motor involvement of a
      peripheral nerve by VZV diagnosed by magnetic resonance imaging with cutaneous
      manifestations in a different dermatomal distribution. To the best of our
      knowledge, there has been no similar case reported in the English radiology
      literature. We suggest that whenever a radiologist notices MRI findings
      suggesting denervation injury and a cause not readily identified, VZV-related
      denervation injury should be included in the differential diagnosis, especially
      in an older immunocompromised patient. 

PMID- 24880714
TI  - Severe kyphotic deformity resulting from collapses of cemented and adjacent
      vertebrae following percutaneous vertebroplasty using calcium phosphate cement. A
      case report.
AB  - Percutaneous vertebroplasty (PVP) has been increasingly performed for the
      treatment of osteoporotic vertebral compression fracture. Despite its minimally
      invasive procedure, several complications associated with PVP have been reported,
      including adjacent-level vertebral fracture. Although rare, recollapse of the
      same vertebrae after PVP has also been reported. However, previous studies have
      not described a case in which collapses of both the cemented vertebrae and
      adjacent-level vertebrae occurred following PVP. Here, we report a rare case of
      severe kyphotic deformity resulting from collapses at the cemented and adjacent
      vertebrae after PVP using calcium phosphate cement (CPC). The patient required a
      highly invasive reconstruction procedure as a salvage surgery. 

PMID- 24880715
TI  - MRI of lesser metatarsophalangeal joint plantar plate tears and associated
      adjacent interspace lesions.
AB  - OBJECTIVE: To identify the variety of second and third intermetatarsal space (IS)
      lesions that may coexist with and without adjacent metatarsophalangeal joint
      (MTP) plantar plate (PP) tears. MATERIALS AND METHODS: One hundred forefoot MRIs
      in 96 patients with metatarsalgia obtained between 30 September 2011 and 21 July
      2012 using 1.5- or 3-T MRI were retrospectively reviewed in consensus by two MSK
      radiologists and one podiatrist (DPM). MRI was evaluated for second and third MTP
      PP tear and the presence/nature of second and third IS lesions. Second and third
      IS neuromas were measured in transverse (trans) dimension. RESULTS: A total of 40
      PP tears were identified: 36 at the second and 4 at the third MTP. Second MTP PP
      tear was identified in 33% of females and 40.5% of males. In the 63 female feet
      there were 21 second MTP PP tears, all of which also had second IS lesions:
      pericapsular fibrosis (16), bursitis (4), and ganglion (1). In the 37 male feet
      there were 15 second MTP PP tears, 14 of which had second IS lesions:
      pericapsular fibrosis (8), bursitis (5), and ganglion (1). There was no definite
      second IS neuroma adjacent to any second MTP PP tear. In females without PP tear,
      there were 24 second (3 mm trans average) and 43 third IS neuromas (4.1 mm trans
      average). In males without PP tear, there were 9 second (3.4 mm trans average)
      and 16 third IS neuromas (4.1 mm trans average). CONCLUSIONS: MTP PP tears
      occurred in 40% of our cases, 90% of which occurred at the second MTP. Almost all
      coexisted with non-neuromatous second IS lesions.

PMID- 24880716
TI  - Serum 25(OH)D3 levels affect treatment outcomes for telaprevir/peg
      interferon/ribavirin combination therapy in genotype 1b chronic hepatitis C.
AB  - BACKGROUND: Close relationships between chronic hepatitis C and vitamin D levels
      have been reported. For genotype 1b infection, the current standard of care is
      pegylated interferon/ribavirin therapy combined with a protease inhibitor. The
      present study analyzed the relationship between outcomes of triple therapy and
      serum 25(OH)D3 levels. METHODS: Factors contributing to sustained virological
      response were investigated in 177 patients with chronic hepatitis C who received
      telaprevir-based triple therapy in this prospective study. RESULTS: The sustained
      virological response rate was 86.9% in patients with 25(OH)D3 levels of >18
      ng/ml; this was higher than the 66.7% in patients with 25(OH)D3 levels of <= 18
      ng/ml (P=0.003). 25(OH)D3 levels and IL28B genotype were identified as
      significantly independent factors contributing to sustained virological response.
      The sustained virological response rate did not differ according to 25(OH)D3
      levels in patients with the IL28B major genotype. The sustained virological
      response rate was 64.9% in patients with the IL28B minor genotype and 25(OH)D3
      levels of >18 ng/ml, and was 38.5% in those with decreased 25(OH)D3 levels
      (P=0.045). CONCLUSIONS: In triple therapy, 25(OH)D3 levels were an independent
      factor contributing to sustained virological response. Of particular note, the
      sustained virological response rate was significantly lower in patients with the
      IL28B minor genotype.

PMID- 24880717
TI  - Molecular diagnostics of the HBB gene in an Omani cohort using bench-top DNA Ion
      Torrent PGM technology.
AB  - Hemoglobinopathies, such as sickle cell disease (SCD) and beta-thalassemia major
      (TM), are severe diseases and the most common autosomal recessive condition
      worldwide and in particular in Oman. Early screening and diagnosis of carriers
      are the key for primary prevention. Once a country-wide population screening
      program is mandated by law, a sequencing technology that can rapidly confirm or
      identify disease-causing mutations for a large number of patients in a short
      period of time will be necessary. While Sanger sequencing is the standard
      protocol for molecular diagnosis, next generation sequencing starts to become
      available to reference laboratories. Using the Ion Torrent PGM sequencer, we have
      analyzed a cohort of 297 unrelated Omani cases and reliably identified mutations
      in the beta-globin (HBB) gene. Our model study has shown that Ion Torrent PGM can
      rapidly sequence such a small gene in a large number of samples using a barcoded
      uni-directional or bi-directional sequence methodology, reducing cost, workload
      and providing accurate diagnosis. Based on our results we believe that the Ion
      Torrent PGM sequencing platform, able to analyze hundreds of patients
      simultaneously for a single disease gene can be a valid molecular screening
      alternative to ABI sequencing in the diagnosis of hemoglobinopathies and other
      genetic disorders in the near future. 

PMID- 24880718
TI  - Quality, cost, and their trade-off in treating AMI and stroke patients in
      European hospitals.
AB  - OBJECTIVES: This study compared the cost and in-hospital mortality of hospital
      care for two major diseases, acute myocardial infarction (AMI) and stroke, by
      pooling patient-level data from five European countries (Finland, France,
      Germany, Spain, and Sweden). We examined whether a cost-quality trade-off existed
      in these countries by comparing hospital-level costs and survival rates, and
      whether hospitals which performed well in terms of cost or quality in treating
      one patient group (AMI) performed well also in treating the other patient group
      (stroke). METHODS: A fixed-effect probit regression model for survival and the
      linear model for log costs were used to calculate indicators for hospital quality
      and cost, which were plotted against each other. FINDINGS: Both with AMI and
      stroke there were remarkable differences between hospitals and countries in (both
      crude and adjusted) rates of patients discharged alive. Swedish and French
      hospitals had lower mortality than hospitals in Germany, Finland and Spain in the
      care of AMI patients. However, a longer length of stay in Spanish and German
      hospitals may bias the results in the two countries. The Finnish hospitals seemed
      to have lower mortality than the other countries' hospitals in the care of stroke
      patients. There was no correlation at either the national or hospital level in
      the quality of treatment of these two diseases. We did not find a clear cost
      quality trade-off. The only notable exception was Sweden, where the costs for AMI
      patients were higher in hospitals with the highest quality of care. CONCLUSIONS:
      Countries should identify the best performing hospitals both in terms of cost and
      quality in order to learn from hospitals that demonstrate better practice. It is
      equally important to better understand the reasons behind the observed
      differences between hospitals in costs and quality.

PMID- 24880719
TI  - The new regulation to investigate potentially beneficial diagnostic and
      therapeutic methods in Germany: up to international standard?
AB  - Funding of diagnostic and therapeutic methods in Germany's statutory health
      insurance (SHI) follows a dichotomy: in outpatient care, only methods with proven
      benefit are reimbursed while in inpatient care, all methods may be provided
      unless they are excluded due to proven harm or lack of benefit. In January 2012,
      a new section 137e was added to the Social Code Book V (SGB V), allowing for the
      inclusion of innovative and potentially beneficial diagnostic or therapeutic
      methods in the SHI benefit basket, while additional evidence regarding their
      effectiveness and safety must be gathered. In 2013, the Federal Joint Committee
      (G-BA) has specified the details of this new approach, which can be considered a
      variety of "Coverage with Evidence Development" (CED). Our comparison with CED
      schemes in selected countries reveals a dependence of the CED implementation on
      the encompassing healthcare system. However, we identify a clear legislative
      foundation, a definitive decision-making body, the possibility to obtain public
      funding, and the preference for high quality study designs as constituting
      factors of an emerging international standard for CED. In addition, it is
      necessary to ensure the suitability of circumstances and technologies for the
      successful application of CED in a clear and transparent way. 

PMID- 24880720
TI  - How should we regulate risk in biomedical research? An ethical analysis of recent
      policy proposals and initiatives.
AB  - The existing regulatory framework for research is increasingly attacked for its
      "one-size-fits-all" approach. Many stakeholders contend that existing regulations
      formulate the same regulatory requirements for research involving very different
      levels of risk, and thereby unnecessarily stifle medical progress. To address
      this criticism, regulators are currently developing more risk-adapted approaches
      to regulating research. A key feature of these approaches is that they aim to
      calibrate subject protections, including ethical review and safety monitoring, to
      the risks that studies pose to participants. Risk-adapted systems of research
      oversight are ethically appealing because they have the potential to promote
      research within the constraints of adequate subject protection. However, this
      potential can only be realized if the complexities surrounding research risk can
      be addressed. The present paper offers the first systematic overview and ethical
      analysis of how European and U.S. regulators approach the development of more
      risk-adapted regulations. The analysis finds that so-called stratified approaches
      are ethically preferable because they specify risk categories with corresponding
      subject protections, and thereby reduce unwarranted variation in how research
      participants are protected in different studies. But the recent proposals for
      stratifying risk and subject protections raise various ethical concerns, for
      example regarding the accuracy of risk categories. Building on this analysis, the
      paper develops recommendations for future policy. 

PMID- 24880721
TI  - Inhibitory effects of a cured antibacterial bonding system on viability and
      metabolic activity of oral bacteria.
AB  - OBJECTIVES: To evaluate the antimicrobial efficacy of Clearfil SE Protect (CP)
      and Clearfil SE Bond (CB) after curing and rinsed against five individual oral
      microorganisms as well as a mixture of bacterial culture prepared from the
      selected test organisms. METHODS: Bacterial suspensions were prepared from single
      species of Streptococcus mutans, Streptococcus sobrinus, Streptococcus gordonii,
      Actinomyces viscosus and Lactobacillus lactis, as well as mixed bacterial
      suspensions from these organisms. Dentin bonding system discs (6 mm*2 mm) were
      prepared, cured, washed and placed on the bacterial suspension of single species
      or multispecies bacteria for 15, 30 and 60 min. MTT, Live/Dead bacterial
      viability (antibacterial effect), and XTT (metabolic activity) assays were used
      to test the two dentin system's antibacterial effect. All assays were done in
      triplicates and each experiment repeated at least three times. Data were
      submitted to ANOVA and Scheffe's f-test (5%). RESULTS: Greater than 40% bacteria
      killing was seen within 15 min, and the killing progressed with increasing time
      of incubation with CP discs. However, a longer (60 min) period of incubation was
      required by CP to achieve similar antimicrobial effect against mixed bacterial
      suspension. CB had no significant effect on the viability or metabolic activity
      of the test microorganisms when compared to the control bacterial culture. CP was
      significantly effective in reducing the viability and metabolic activity of the
      test organisms. SIGNIFICANCE: The results demonstrated the antimicrobial efficacy
      of CP both on single and multispecies bacterial culture. CP may be beneficial in
      reducing bacterial infections in cavity preparations in clinical dentistry.

PMID- 24880723
TI  - Water and waste load allocation in rivers with emphasis on agricultural return
      flows: application of fractional factorial analysis.
AB  - In this paper, a new methodology is developed to handle parameter and input
      uncertainties in water and waste load allocation (WWLA) in rivers by using
      factorial interval optimization and the Soil, Water, Atmosphere, and Plant (SWAP)
      simulation model. A fractional factorial analysis is utilized to provide detailed
      effects of uncertain parameters and their interaction on the optimization model
      outputs. The number of required optimizations in a fractional factorial analysis
      can be much less than a complete sensitivity analysis. The most important
      uncertain inputs and parameters can be also selected using a fractional factorial
      analysis. The uncertainty of the selected inputs and parameters should be
      incorporated real time water and waste load allocation. The proposed methodology
      utilizes the SWAP simulation model to estimate the quantity and quality of each
      agricultural return flow based on the allocated water quantity and quality. In
      order to control the pollution loads of agricultural dischargers, it is assumed
      that a part of their return flows can be diverted to evaporation ponds. Results
      of applying the methodology to the Dez River system in the southwestern part of
      Iran show its effectiveness and applicability for simultaneous water and waste
      load allocation in rivers. It is shown that in our case study, the number of
      required optimizations in the fractional factorial analysis can be reduced from
      64 to 16. Analysis of the interactive effects of uncertainties indicates that in
      a low flow condition, the upstream water quality would have a significant effect
      on the total benefit of the system. 

PMID- 24880722
TI  - Collagen modifications in postmenopausal osteoporosis: advanced glycation
      endproducts may affect bone volume, structure and quality.
AB  - The classic model of postmenopausal osteoporosis (PM-OP) starts with the
      depletion of estrogen, which in turn stimulates imbalanced bone remodeling,
      resulting in loss of bone mass/volume. Clinically, this leads to fractures
      because of structural weakness. Recent work has begun to provide a more complete
      picture of the mechanisms of PM-OP involving oxidative stress and collagen
      modifications known as advanced glycation endproducts (AGEs). On one hand, AGEs
      may drive imbalanced bone remodeling through signaling mediated by the receptor
      for AGEs (RAGE), stimulating resorption and inhibiting formation. On the other
      hand, AGEs are associated with degraded bone material quality. Oxidative stress
      promotes the formation of AGEs, inhibits normal enzymatically derived
      crosslinking and can degrade collagen structure, thereby reducing fracture
      resistance. Notably, there are multiple positive feedback loops that can
      exacerbate the mechanisms of PM-OP associated with oxidative stress and AGEs.
      Anti-oxidant therapies may have the potential to inhibit the oxidative stress
      based mechanisms of this disease. 

PMID- 24880724
TI  - Modelling the dispersion of treated wastewater in a shallow coastal wind-driven
      environment, Geographe Bay, Western Australia: implications for environmental
      management.
AB  - Numerical models are useful for predicting the transport and fate of contaminants
      in dynamic marine environments, and are increasingly a practical solution to
      environmental impact assessments. In this study, a three-dimensional hydrodynamic
      model and field data were used to validate a far-field dispersion model that, in
      turn, was used to determine the fate of treated wastewater (TWW) discharged to
      the ocean via a submarine ocean outfall under hypothetical TWW flows. The models
      were validated with respect to bottom and surface water current speed and
      direction, and in situ measurements of total nitrogen and faecal coliforms.
      Variations in surface and bottom currents were accurately predicted by the model
      as were nutrient and coliform concentrations. Results indicated that the ocean
      circulation was predominately wind driven, evidenced by relatively small
      oscillations in the current speeds along the time-scale of the tide, and that
      dilution mixing zones were orientated in a predominantly north-eastern direction
      from the outfall and parallel to the coastline. Outputs of the model were used to
      determine the 'footprint' of the TWW plume under a differing discharge scenario
      and, particularly, whether the resultant changes in TWW contaminants, total
      nitrogen and faecal coliforms would meet local environmental quality objectives
      (EQO) for ecosystem integrity, shellfish harvesting and primary recreation.
      Modelling provided a practical solution for predicting the dilution of
      contaminants under a hypothetical discharge scenario and a means for determining
      the aerial extent of exclusion zones, where the EQOs for shellfish harvesting and
      primary recreation may not always be met. Results of this study add to the
      understanding of regional discharge conditions and provide a practical case study
      for managing impacts to marine environments under a differing TWW discharge
      scenario, in comparison to an existing scenario. 

PMID- 24880726
TI  - Assessment of water quality using multivariate statistical techniques in the
      coastal region of Visakhapatnam, India.
AB  - The present study was intended to develop a Water Quality Index (WQI) for the
      coastal water of Visakhapatnam, India from multiple measured water quality
      parameters using different multivariate statistical techniques. Cluster analysis
      was used to classify the data set into three major groups based on similar water
      quality characteristics. Discriminant analysis was used to generate a
      discriminant function for developing a WQI. Discriminant analysis gave the best
      result for analyzing the seasonal variation of water quality. It helped in data
      reduction and found the most discriminant parameters responsible for seasonal
      variation of water quality. Coastal water was classified into good, average, and
      poor quality considering WQI and the nutrient load. The predictive capacity of
      WQI was proved with random samples taken from coastal areas. High concentration
      of ammonia in surface water during winter was attributed to nitrogen fixation by
      the phytoplankton bloom which resulted due to East India Coastal Current. This
      study brings out the fact that water quality in the coastal region not only
      depends on the discharge from different pollution sources but also on the
      presence of different current patterns. It also illustrates the usefulness of WQI
      for analyzing the complex nutrient data for assessing the coastal water and
      identifying different pollution sources, considering reasons for seasonal
      variation of water quality. 

PMID- 24880725
TI  - Effect of pH, ionic strength, and background electrolytes on Cr(VI) and total
      chromium removal by acorn shell of Quercus crassipes Humb. & Bonpl.
AB  - The ability of Quercus crassipes acorn shells (QCS) to remove Cr(VI) and total
      chromium from aqueous solutions was investigated as a function of the solution
      pH, ionic strength, and background electrolytes. It was found that Cr(VI) and
      total chromium removal by QCS depended strongly on the pH of the solution. Cr(VI)
      removal rate increased as the solution pH decreased. The optimum pH for total
      chromium removal varied depending on contact time. NaCl ionic strengths lower
      than 200 mM did not affect chromium removal. The presence of 20 mM monovalent
      cations and anions, and of divalent cations, slightly decreased the removal of
      Cr(VI) and total chromium by QCS; in contrast, divalent anions (SO4(2-), PO4(2-),
      CO3(2-)) significantly affected the removal of Cr(VI) and total chromium. The
      biosorption kinetics of chromium ions followed the pseudo-second-order model at
      all solution pH levels, NaCl ionic strengths and background electrolytes tested.
      Results suggest that QCS may be a potential low-cost biosorbent for the removal
      of Cr(VI) and total chromium from aqueous solutions containing various
      impurities.

PMID- 24880727
TI  - Sudden-onset bilateral deafness revealing early neurosyphilis.
AB  - INTRODUCTION: Rapid-onset of sensorineural hearing loss in a patient at risk of
      genital or oral exposure to treponema can be secondary to early neurosyphilis,
      for which delayed treatment may result in irreversible sequelae. SUMMARY OF THE
      CASE REPORT: A 40-year-old, HIV seropositive man with a CD4 lymphocyte count
      greater than 500/mm(3) presented with rapid-onset of bilateral sensorineural
      hearing loss over a period of one week. Otorhinolaryngological examination was
      normal. The audiogram showed bilateral hearing loss of 25 and 30 decibels,
      respectively. He subsequently developed loss of visual acuity, leading to the
      diagnosis of syphilitic meningitis affecting the optic and auditory nerves.
      DISCUSSION: In about one half of cases, neurosyphilis is an early manifestation
      of the disease occurring several weeks or months after contamination. Rapid- or
      even sudden-onset of hearing loss may be due to auditory neuritis. Clinical
      interview and syphilis serology in a patient at risk of exposure can allow rapid
      diagnosis and treatment, consisting of two weeks parenteral penicillin. Recovery
      of hearing loss is inconstant but can be complete.

PMID- 24880728
TI  - Evaluation of two automated methods for PET region of interest analysis.
AB  - Manual definition of regions of interest (ROIs) has been considered the reference
      standard method in PET data evaluation. The method is labor-intensive, prone to
      rater bias and may show low reproducibility. Automated template-based methods for
      ROI definition may overcome these limitations. The aim of this study was to
      validate the two automated methods FreeSurfer and the AAL template for definition
      of ROIs for the PET data analysis. PET data obtained using the radioligands
      [11C]AZD2184 (amyloid-beta radioligand) and [11C]AZ10419369 (5-HT1B receptor
      radioligand) were evaluated. PET measurements acquired on one high and one lower
      resolution PET system were included. Outcome measures obtained using automated
      methods were compared to those obtained using manual ROIs, using linear
      regression analysis, intraclass correlation coefficients, and repeated measures
      ANOVA. ROIs provided by the automatic methods were larger than the manually
      delineated regions, which in some cases introduced biased estimates of the
      outcome measures. However, with the exception of the caudate, both AAL and
      FreeSurfer generally provided outcome measures that were in good agreement to
      those obtained from manually delineated ROIs, as long as the manually defined
      cerebellum was used as a reference region. Both AAL and FreeSurfer can be used
      for quantification of PET data, with similar accuracy in the estimates of outcome
      measures. Thus, the choice of method could be based upon necessity of fast
      analysis as provided by AAL, or more detailed ROIs and measures of cortical
      thickness as provided by FreeSurfer.

PMID- 24880729
TI  - Anion charge storage through oxygen intercalation in LaMnO3 perovskite
      pseudocapacitor electrodes.
AB  - Perovskite oxides have attracted significant attention as energy conversion
      materials for metal-air battery and solid-oxide fuel-cell electrodes owing to
      their unique physical and electronic properties. Amongst these unique properties
      is the structural stability of the cation array in perovskites that can
      accommodate mobile oxygen ions under electrical polarization. Despite oxygen ion
      mobility and vacancies having been shown to play an important role in catalysis,
      their role in charge storage has yet to be explored. Herein we investigate the
      mechanism of oxygen-vacancy-mediated redox pseudocapacitance for a nanostructured
      lanthanum-based perovskite, LaMnO3. This is the first example of anion-based
      intercalation pseudocapacitance as well as the first time oxygen intercalation
      has been exploited for fast energy storage. Whereas previous pseudocapacitor and
      rechargeable battery charge storage studies have focused on cation intercalation,
      the anion-based mechanism presented here offers a new paradigm for
      electrochemical energy storage. 

PMID- 24880730
TI  - Ultrahigh interlayer friction in multiwalled boron nitride nanotubes.
AB  - Friction at the nanoscale has revealed a wealth of behaviours that depart
      strongly from the long-standing macroscopic laws of Amontons-Coulomb. Here, by
      using a 'Christmas cracker'-type of system in which a multiwalled nanotube is
      torn apart between a quartz-tuning-fork-based atomic force microscope (TF-AFM)
      and a nanomanipulator, we compare the mechanical response of multiwalled carbon
      nanotubes (CNTs) and multiwalled boron nitride nanotubes (BNNTs) during the
      fracture and telescopic sliding of the layers. We found that the interlayer
      friction for insulating BNNTs results in ultrahigh viscous-like dissipation that
      is proportional to the contact area, whereas for the semimetallic CNTs the
      sliding friction vanishes within experimental uncertainty. We ascribe this
      difference to the ionic character of the BN, which allows charge localization.
      The interlayer viscous friction of BNNTs suggests that BNNT membranes could serve
      as extremely efficient shock-absorbing surfaces. 

PMID- 24880731
TI  - Acoustic metasurface with hybrid resonances.
AB  - An impedance-matched surface has the property that an incident wave generates no
      reflection. Here we demonstrate that by using a simple construction, an
      acoustically reflecting surface can acquire hybrid resonances and becomes
      impedance-matched to airborne sound at tunable frequencies, such that no
      reflection is generated. Each resonant cell of the metasurface is deep
      subwavelength in all its spatial dimensions, with its thickness less than the
      peak absorption wavelength by two orders of magnitude. As there can be no
      transmission, the impedance-matched acoustic wave is hence either completely
      absorbed at one or multiple frequencies, or converted into other form(s) of
      energy, such as an electrical current. A high acoustic-electrical energy
      conversion efficiency of 23% is achieved. 

PMID- 24880732
TI  - Stretchable liquid-crystal blue-phase gels.
AB  - Liquid-crystalline polymers are materials of considerable scientific interest and
      technological value. An important subset of these materials exhibit rubber-like
      elasticity, combining the optical properties of liquid crystals with the
      mechanical properties of rubber. Moreover, they exhibit behaviour not seen in
      either type of material independently, and many of their properties depend
      crucially on the particular mesophase employed. Such stretchable liquid
      crystalline polymers have previously been demonstrated in the nematic, chiral
      nematic, and smectic mesophases. Here, we report the fabrication of a stretchable
      gel of blue phase I, which forms a self-assembled, three-dimensional photonic
      crystal that remains electro-optically switchable under a moderate applied
      voltage, and whose optical properties can be manipulated by an applied strain. We
      also find that, unlike its undistorted counterpart, a mechanically deformed blue
      phase exhibits a Pockels electro-optic effect, which sets out new theoretical
      challenges and possibilities for low-voltage electro-optic devices. 

PMID- 24880734
TI  - Association mapping in crop plants: opportunities and challenges.
AB  - The research area of association mapping (AM) is currently receiving major
      attention for genetic studies of quantitative traits in all major crops. However,
      the level of success and utility of AM achieved for crop improvement is not
      comparable to that in the area of human health care for diagnosis of complex
      human diseases. These AM studies in plants, as in humans, became possible due to
      the availability of DNA-based molecular markers and a variety of sophisticated
      statistical tools that are evolving on a regular basis. In this chapter, we first
      briefly review the significance of a variety of populations that are used in AM
      studies, then briefly describe the molecular markers and high-throughput
      genotyping strategies, and finally describe the approaches used for AM studies.
      The major part of the chapter is, however, devoted to analysis of reasons why the
      results of AM have been underutilized in plant breeding. We also examine the
      opportunities available and challenges faced while using AM for crop improvement
      programs. This includes a detailed discussion of the issues that have plagued AM
      studies, and the solutions that have become available to deal with these issues,
      so that in future, the results of AM studies may prove increasingly fruitful for
      crop improvement programs. 

PMID- 24880733
TI  - Neurogenetics of female reproductive behaviors in Drosophila melanogaster.
AB  - We follow an adult Drosophila melanogaster female through the major reproductive
      decisions she makes during her lifetime, including habitat selection,
      precopulatory mate choice, postcopulatory physiological changes, polyandry, and
      egg-laying site selection. In the process, we review the molecular and neuronal
      mechanisms allowing females to integrate signals from both environmental and
      social sources to produce those behavioral outputs. We pay attention to how an
      understanding of D. melanogaster female reproductive behaviors contributes to a
      wider understanding of evolutionary processes such as pre- and postcopulatory
      sexual selection as well as sexual conflict. Within each section, we attempt to
      connect the theories that pertain to the evolution of female reproductive
      behaviors with the molecular and neurobiological data that support these
      theories. We draw attention to the fact that the evolutionary and mechanistic
      basis of female reproductive behaviors, even in a species as extensively studied
      as D. melanogaster, remains poorly understood. 

PMID- 24880735
TI  - The miRNA-mediated cross-talk between transcripts provides a novel layer of
      posttranscriptional regulation.
AB  - Endogenously expressed transcripts that are posttranscriptionally regulated by
      the same microRNAs (miRNAs) will, in principle, compete for the binding of their
      shared small noncoding RNA regulators and modulate each other's abundance.
      Recently, the levels of some coding as well as noncoding transcripts have indeed
      been found to be regulated in this way. Transcripts that engage in such
      regulatory interactions are referred to as competitive endogenous RNAs (ceRNAs).
      This novel layer of posttranscriptional regulation has been shown to contribute
      to diverse aspects of organismal and cellular biology, despite the number of
      functionally characterized ceRNAs being as yet relatively low. Importantly,
      increasing evidence suggests that the dysregulation of some ceRNA interactions is
      associated with disease etiology, most preeminently with cancer. Here we review
      how posttranscriptional regulation by miRNAs contributes to the cross-talk
      between transcripts and review examples of known ceRNAs by highlighting the
      features underlying their interactions and what might be their biological
      relevance. 

PMID- 24880736
TI  - Essential letters in the fungal alphabet: ABC and MFS transporters and their
      roles in survival and pathogenicity.
AB  - Fungi depend heavily on their ability to exploit resources that may become
      available to them in their myriad of possible lifestyles. Whether this requires
      simple uptake of sugars as saprobes or competition for host-derived carbohydrates
      or peptides, fungi must rely on transporters that effectively allow the fungus to
      accumulate such nutrients from their environments. In other cases, fungi secrete
      compounds that facilitate their interactions with potential hosts and/or
      neutralize their competition. Finally, fungi that find themselves on the
      receiving end of insults, from hosts, competitors, or the overall environment are
      better served if they can get rid of such toxins or xenobiotics. In this chapter,
      we update studies on the most ubiquitous transporters, the ABC and MFS
      superfamilies. In addition, we discuss the importance of subsets of these
      proteins with particular relevance to plant pathogenic fungi. The availability of
      ever-increasing numbers of sequenced fungal genomes, combined with high
      throughput methods for transcriptome analysis, provides insights previously
      inaccessible prior to the -omics era. As examples of such broader perspectives,
      we point to revelations about exploitive use of sugar transporters by plant
      pathogens, expansion of trichothecene efflux pumps in fungi that do not produce
      these mycotoxins, and the discovery of a fungal-specific oligopeptide transporter
      class that, so far, is overrepresented in the plant pathogenic fungi. 

PMID- 24880737
TI  - Unisexual reproduction.
AB  - Sexual reproduction is ubiquitous throughout the eukaryotic kingdom, but the
      capacity of pathogenic fungi to undergo sexual reproduction has been a matter of
      intense debate. Pathogenic fungi maintained a complement of conserved meiotic
      genes but the populations appeared to be clonally derived. This debate was
      resolved first with the discovery of an extant sexual cycle and then unisexual
      reproduction. Unisexual reproduction is a distinct form of homothallism that
      dispenses with the requirement for an opposite mating type. Pathogenic and
      nonpathogenic fungi previously thought to be asexual are able to undergo robust
      unisexual reproduction. We review here recent advances in our understanding of
      the genetic and molecular basis of unisexual reproduction throughout fungi and
      the impact of unisex on the ecology and genomic evolution of fungal species. 

PMID- 24880738
TI  - Uraemic toxins and cardiovascular disease across the chronic kidney disease
      spectrum: an observational study.
AB  - BACKGROUND AND AIMS: There is a growing body of evidence supporting the
      nephrovascular toxicity of indoxyl sulphate (IS) and p-cresyl sulphate (PCS).
      Nonetheless, a comprehensive description of how these toxins accumulate over the
      course of chronic kidney disease (CKD) is lacking. METHODS AND RESULTS: This
      cross-sectional observational study included a convenience sample of 327
      participants with kidney function categorised as normal, non-dialysis CKD and end
      stage kidney disease (ESKD). Participants underwent measurements of serum total
      and free IS and PCS and assessment of cardiovascular history and structure
      (carotid intima-media thickness [cIMT, a measure of arterial stiffness]), and
      endothelial function (brachial artery reactivity [flow-mediated dilation (BAR
      FMD); glyceryl trinitrate (BAR-GTN)]). Across the CKD spectrum there was a
      significant increase in both total and free IS and PCS and their free fractions,
      with the highest levels observed in the ESKD population. Within each CKD stage,
      concentrations of PCS, total and free, were significantly greater than IS (all p
      < 0.01). Both IS and PCS, free and total, were correlated with BAR-GTN (ranging
      from r = -0.33 to -0.44) and cIMT (r = 0.19 to 0.21), even after adjusting for
      traditional risk factors (all p < 0.01). Further, all toxins were independently
      associated with the presence of cardiovascular disease (all p < 0.02).
      CONCLUSION: More advanced stages of CKD are associated with progressive increases
      in total and free serum IS and PCS, as well as increases in their free fractions.
      Total and free serum IS and PCS were independently associated with structural and
      functional markers of cardiovascular disease. Studies of therapeutic
      interventions targeting these uraemic toxins are warranted.

PMID- 24880739
TI  - Association of anthropometric measures and hemostatic factors in postmenopausal
      women: a longitudinal study.
AB  - BACKGROUND AND AIMS: Obesity has been associated with increased levels of
      hemostatic factors. However, few studies have compared change in different
      anthropometric measures of adiposity in relation to change in levels of
      hemostatic factors. Our aim was to examine prospectively the association of
      change in body mass index (BMI), waist-hip ratio (WHR), waist circumference (WC),
      and waist circumference-height ratio (WHtR) with change in markers of hemostasis
      in a population of postmenopausal women. METHODS AND RESULTS: A subsample of
      women in the Women's Health Initiative (WHI) cohort had fasting blood samples and
      anthropometric measurements obtained at multiple time points over 12.8 years of
      follow-up. Of these, we studied the 2593 women who were not in the intervention
      arm of any WHI clinical trial. Their blood samples were used to measure plasma
      fibrinogen, factor VII antigen activity, and factor VII concentration at
      baseline, and at years 1, 3, and 6. We conducted mixed-effects linear regression
      analyses to examine the longitudinal association between change in anthropometric
      factors and change in hemostatic factors, adjusting for a wide range of potential
      confounding factors. In longitudinal analyses using repeated measures, change in
      BMI, WC, and WHtR were all positively associated with change in all 3 hemostatic
      factors. Change in anthropometric variables was most strongly associated with
      change in fibrinogen. CONCLUSIONS: Our results suggest that an increase in
      adiposity over time is robustly associated with increased levels of hemostatic
      factors. Registration number of clinical trial: NCT00000611.

PMID- 24880740
TI  - Changes in high-density-lipoprotein cholesterol upon statin treatment in type 2
      diabetic patients: a meta-analysis.
AB  - BACKGROUND AND AIM: To investigate the diversity of change in high-density
      lipoprote in cholesterol (HDL-C) after statin treatment in patients with type 2
      diabetes mellitus (T2DM). METHODS AND RESULTS: A systemic review searched for
      trials that reported a serum change in HDL-C in patients with T2DM after statin
      treatment, and extracted data for meta-analysis. Of 6709 articles surveyed, 160
      articles were identified as eligible articles. In the analysis of simvastatin,
      serum HDL-C was increased in Non-Asian and Asian patients with T2DM by 2.17 mg/dl
      (95% CI 1.43 ~ 2.90 mg/dl, p < 0.001) and 2.31 mg/dl (95% CI 1.37 ~ 3.25 mg/dl, p
      < 0.001), respectively. In the analysis of atorvastatin, although significant,
      serum HDL-C was subtly increased in Non-Asian patients with T2DM by 1.14 mg/dl
      (95% CI 0.28 ~ 2.01 mg/dl, p = 0.010) mg/dl; however, atorvastatin treatment did
      not significantly change the serum HDL-C by 0.12 mg/dl (95% CI -1.04 ~ 1.27
      mg/dl, p = 0.839) mg/dl in Asian patients with T2DM. According to meta-regression
      analysis, the baseline HDL-C did not affect the change in serum HDL-C in Asian
      patients with T2DM after either simvastatin or atorvastatin treatment. However,
      contrary to simvastatin, the coefficient of regression (r) showed a significant
      negative association (r = -0.18; 95% CI -0.32 to -0.04; p = 0.01) between
      baseline HDL-C and the change of HDL-C in non-Asian patients with T2DM after
      atorvastatin treatment. CONCLUSION: We have demonstrated for the first time that
      there may be a discrepancy in the change of serum HDL-C in Asian patients with
      T2DM after atorvastatin treatment.

PMID- 24880741
TI  - [Treatment of subcutaneous calcinosis in systemic disorders].
AB  - Calcinosis cutis constitutes a heterogeneous group of chronic disorder. It can be
      associated with disturbance of calcium and/or phosphate metabolism (metastatic,
      tumor calcinosis, calciphylaxis) but may also develop without any metabolic
      disorder, in particular during the course of connective tissue diseases. Among
      these, the most common are dermatomyositis and the limited form of systemic
      sclerosis. The physiopathology of calcinosis cutis is poorly known. It can cause
      pain, chronic ulcerations, infections, which are sources of sometimes major
      disability. Treatment of calcinosis is challenging because no drug has been shown
      to be reliably effective in stopping the progression or decreasing dystrophic
      calcifications in controlled trials. Calcium blocker and colchicine are generally
      prescribed as the first line systemic therapy. In the localized forms of small
      lesions, surgical excision is often effective and sometimes preceded by local
      treatments (laser therapy, extracorporeal shock wave lithotripsy, topical sodium
      thiosulfate, etc.) or systemic treatment (minocycline, warfarine). When
      calcinosis is disseminated, it may require additional treatments (aluminium
      hydroxyde, bisphosphonates) possibly associated with surgery in case of large
      lesions. Time to response may be prolonged from weeks to months. The calcinosis
      cutis can lead to secondary infection, pain and functional disability that have
      to be prevented. 

PMID- 24880742
TI  - Multi-modality functional image guided dose escalation in the presence of
      uncertainties.
AB  - BACKGROUND AND PURPOSE: In order to increase local tumour control by radiotherapy
      without increasing toxicity, it appears promising to harness functional imaging
      (FI) to guide dose to sub-volumes of the target with a high tumour load and
      perhaps de-escalate dose to low risk volumes, in order to maximise the efficiency
      of the deposited radiation dose. METHODS AND MATERIALS: A number of problems have
      to be solved to make focal dose escalation (FDE) efficient and safe: (1) how to
      combine ambiguous information from multiple imaging modalities; (2) how to take
      into account uncertainties of FI based tissue classification; (3) how to account
      for geometric uncertainties in treatment delivery; (4) how to add complementary
      FI modalities to an existing scheme. A generic optimisation concept addresses
      these points and is explicitly designed for clinical efficacy and for lowering
      the implementation threshold to FI-guided FDE. It combines classic tumour control
      probability modelling with a multi-variate logistic regression model of FI
      accuracy and an uncomplicated robust optimisation method. RESULTS: Its key
      elements are (1) that dose is deposited optimally when it achieves equivalent
      expected effect everywhere in the target volume and (2) that one needs to cap the
      certainty about the absence of tumour anywhere in the target region. For
      illustration, an example of a PET/MR-guided FDE in prostate cancer is given.
      CONCLUSIONS: FDE can be safeguarded against FI uncertainties, at the price of a
      limit on the sensible dose escalation.

PMID- 24880743
TI  - Erratum to: A Preliminary Study of an Integrated and Culturally Attuned Cognitive
      Behavioral Group Treatment for Chinese Problem Gamblers in Hong Kong.

PMID- 24880744
TI  - Gambling and Problem Gambling in the United States: Changes Between 1999 and
      2013.
AB  - Telephone surveys of US adults were conducted in 1999-2000 and again in 2011
      2013. The same questions and methods were used so as to make the surveys
      comparable. There was a reduction in percentage of past-year gambling and in
      frequency of gambling. Rates of problem gambling remained stable. Lottery was
      included among the specific types of gambling for which past year participation
      and frequency of play declined. Internet gambling was the only form of gambling
      for which the past-year participation rate increased. The average win/loss
      increased for several forms of gambling, providing a modest indication that
      gamblers were betting more, albeit less frequently. Between the two surveys, the
      rates of past-year participation in gambling declined markedly for young adults.
      In both surveys, rates of problem gambling were higher for males than females,
      and this difference increased markedly between surveys as problem gambling rates
      increased for males and decreased for females. For the combined surveys, rates of
      problem gambling were highest for blacks and Hispanics and lowest for whites and
      Asians. In both surveys, the rates of problem gambling declined as socio-economic
      status became higher. Possible explanations for these trends are discussed. 

PMID- 24880745
TI  - Risk Gambling and Personality: Results from a Representative Swedish Sample.
AB  - The association between personality and gambling has been explored previously.
      However, few studies are based on representative populations. This study aimed at
      examining the association between risk gambling and personality in a
      representative Swedish population. A random Swedish sample (N = 19,530) was
      screened for risk gambling using the Lie/Bet questionnaire. The study sample (N =
      257) consisted of those screening positive on Lie/Bet and completing a postal
      questionnaire about gambling and personality (measured with the NODS-PERC and the
      HP5i respectively). Risk gambling was positively correlated with Negative
      Affectivity (a facet of Neuroticism) and Impulsivity (an inversely related facet
      of Conscientiousness), but all associations were weak. When taking age and gender
      into account, there were no differences in personality across game preference
      groups, though preferred game correlated with level of risk gambling. Risk
      gamblers scored lower than the population norm data with respect to Negative
      Affectivity, but risk gambling men scored higher on Impulsivity. The association
      between risk gambling and personality found in previous studies was corroborated
      in this study using a representative sample. We conclude that risk and problem
      gamblers should not be treated as a homogeneous group, and prevention and
      treatment interventions should be adapted according to differences in
      personality, preferred type of game and the risk potential of the games.

PMID- 24880746
TI  - Physiological and pathological functions of NADPH oxidases during myocardial
      ischemia-reperfusion.
AB  - Oxidative stress, the presence of reactive oxygen species (ROS) in excess of the
      antioxidant capacity in the heart induces myocardial damage, accumulation of
      which leads to ischemic heart disease and heart failure. NADPH oxidase (Nox) 2
      and 4 are the major sources of O2- and H2O2 in the heart and play a crucial role
      in the regulation of growth and death in cardiomyocytes. Both Nox2 and Nox4 are
      upregulated in response to ischemia-reperfusion (I/R), thereby contributing to
      ROS production and consequent myocardial injury. Suppression of either one of
      them can reduce ROS and I/R injury in the heart. Importantly, however, a minimum
      level of ROS production by either Nox2 or Nox4 is essential for the activation of
      HIF-1alpha and inhibition of PPARalpha during I/R, such that combined suppression
      of both Nox2 and Nox4 exacerbates myocardial I/R injury. Thus, either excessive
      activation or suppression of Noxs below physiological levels can induce cardiac
      injury. Here we discuss both detrimental and salutary functions of Nox isoforms
      during myocardial I/R.

PMID- 24880748
TI  - Acute parkinsonism as first manifestation of systemic lupus erythematosus
      unmasked by CMV infection.

PMID- 24880747
TI  - Ischemic stroke associated with immune thrombocytopenia: lesion patterns and
      characteristics.
AB  - Although the patients with immune thrombocytopenia (ITP) have a very low platelet
      count, which usually causes hemorrhagic complications, they occasionally
      experience ischemic stroke. However, the mechanism underlying ITP-related
      ischemic stroke (ITP-IS) has not been fully clarified. We aim to elucidate the
      ITP-IS mechanism by analyzing the ischemic lesion patterns and clinical
      characteristics. We assessed consecutive first-ever acute ischemic stroke (AIS)
      patients with ITP admitted to Seoul National University Hospital between October
      2002 and October 2011. The stroke lesion pattern and clinical characteristics of
      ITP-IS patients were analyzed. Of the 2,185 patients with first-ever AIS, seven
      patients (4 women) with ITP-IS were identified. Of these seven patients, 3 (43 %)
      who were classified as undetermined stroke etiology indicated an embolic stroke
      pattern, and had no remarkable atherosclerotic risk factors, no steno-occlusive
      lesions in their relevant artery, and no cardioembolic etiologies or conditions
      causing secondary ITP. Moreover, compared with the patients without ITP, the
      patients with ITP were younger and had lower platelet counts. Thus, we noted that
      ITP is a rare cause of ischemic stroke, which primarily occurs due to the
      development of a thromboembolism in the brain. We believe that this paradoxical
      mechanism of ITP-associated thrombus formation requires further investigation.

PMID- 24880749
TI  - Lithium carbonate in the management of cannabis withdrawal: a randomized placebo
      controlled trial in an inpatient setting.
AB  - RATIONALE: Preclinical studies suggest that lithium carbonate (lithium) can
      reduce precipitated cannabinoid withdrawal in rats by stimulating release of the
      neuropeptide oxytocin, while two open-label studies indicate lithium may
      ameliorate cannabis withdrawal symptoms in humans. OBJECTIVES: This study was
      conducted to examine the efficacy and safety of lithium in the inpatient
      management of cannabis withdrawal and to determine whether lithium affects plasma
      oxytocin and the rate of elimination of plasma cannabinoids during abstinence.
      METHODS: Treatment-seeking cannabis-dependent adults (n = 38) were admitted for 8
      days to an inpatient withdrawal unit and randomized to either oral lithium (500
      mg) or placebo given twice a day under double-blind randomized controlled trial
      (RCT) conditions. Primary outcomes included withdrawal severity [cannabis
      withdrawal scale (CWS)], rates of detoxification completion, and adverse events.
      Plasma cannabinoids, plasma oxytocin and serum lithium levels were measured
      repeatedly over admission. Follow-up research interviews were conducted at 14,
      30, and 90 days postdischarge. RESULTS: Lithium did not significantly affect
      total CWS scores relative to placebo, although it significantly reduced
      individual symptoms of "loss of appetite," "stomach aches," and
      "nightmares/strange dreams." No significant group differences were found in
      treatment retention or adverse events. Lithium did not increase plasma oxytocin
      levels nor influence the rate of elimination of cannabinoids. Both placebo- and
      lithium-treated participants showed reduced levels of cannabis use (verified by
      urinalysis) and improved health and psychosocial outcomes at 30- and 90-day
      follow-up relative to pretreatment baselines. CONCLUSIONS: Despite the strong
      rationale for the present study, the efficacy of lithium over placebo in the
      management of cannabis withdrawal was not demonstrated.

PMID- 24880751
TI  - Role of VEGF and VEGFR2 Receptor in Reversal of ALS-CSF Induced Degeneration of
      NSC-34 Motor Neuron Cell Line.
AB  - Vascular endothelial growth factor (VEGF), the well-known angiogenic factor is
      both neurotrophic and neuroprotective. Altered VEGF signalling is implicated in
      the pathogenesis of amyotrophic lateral sclerosis (ALS), a fatal degenerative
      disease of motor neurons. We have shown earlier that VEGF protects NSC-34 motor
      neuronal cell line, when exposed to cerebrospinal fluid (CSF) from sporadic ALS
      patients (ALS-CSF). Here, we have investigated the consequences of ALS-CSF and
      VEGF supplementation on the VEGFR2 receptor and endogenous VEGF expression. ALS
      CSF caused significant down-regulation of VEGFR2 as well as the Calbindin-D28K
      levels, but not endogenous VEGF. Exogenous supplementation restored the depletion
      of VEGFR2 and Calbindin-D28K with a concomitant up-regulation of endogenous VEGF.
      The up-regulated caspase 3 in the ALS-CSF group was reinstated to basal levels
      along with a significant reduction in the number of TUNEL-positive cells.
      Electron photomicrographs of ALS-CSF-exposed cells divulged presence of
      cytoplasmic vacuoles alongside severe damage to organelles like mitochondria,
      endoplasmic reticulum, etc. Substantial recovery of most of the damaged
      organelles was noted in response to VEGF supplementation. While the enhancement
      in endogenous VEGF levels highlights the autocrine functions, the up-regulation
      of VEGFR2 receptor emphasizes the paracrine functions of VEGF in modulating its
      neuroprotective effect against ALS-CSF. The revival of cellular organellar
      structure, increased calbindin expression and enhanced survival in response to
      VEGF supplementation consolidates the opinion that VEGF indeed has a therapeutic
      potential in sporadic ALS. 

PMID- 24880750
TI  - Radio-neuroprotective effect of L-alpha-glycerylphosphorylcholine (GPC) in an
      experimental rat model.
AB  - Ionizing radiation plays a major role in the treatment of brain tumors, but side
      effects may restrict the efficacy of therapy. In the present study, our goals
      were to establish whether the administration of L-alpha-glycerylphosphorylcholine
      (GPC) can moderate or prevent any of the irradiation-induced functional and
      morphological changes in a rodent model of hippocampus irradiation. Anesthetized
      adult (6-weeks-old) male Sprague-Dawley rats were subjected to 40 Gy irradiation
      of one hemisphere of the brain, without or with GPC treatment (50 mg/kg bw by
      gavage), the GPC treatment continuing for 4 months. The effects of this partial
      rat brain irradiation on the spatial orientation and learning ability of the rats
      were assessed with the repeated Morris water maze (MWM) test. Histopathologic
      (HP) evaluation based on hematoxylin-eosin and Luxol blue staining was performed
      4 months after irradiation. The 40 Gy irradiation resulted in a moderate
      neurological deficit at the levels of both cognitive function and morphology 4
      months after the irradiation. The MWM test proved to be a highly sensitive tool
      for the detection of neurofunctional impairment. The site navigation of the rats
      was impaired by the irradiation, but the GPC treatment markedly decreased the
      cognitive impairment. HP examination revealed lesser amounts of macrophage
      density, reactive gliosis, calcification and extent of demyelination in the GPC
      treated group. GPC treatment led to significant protection against the cognitive
      decline and cellular damage, evoked by focal brain irradiation at 40 Gy dose
      level. Our study warrants further research on the protective or mitigating
      effects of GPC on radiation injuries.

PMID- 24880754
TI  - Age-related behavioural and neurofunctional patterns of second language word
      learning: different ways of being successful.
AB  - This study aimed at investigating the neural basis of word learning as a function
      of age and word type. Ten young and ten elderly French-speaking participants were
      trained by means of a computerized Spanish word program. Both age groups reached
      a similar naming accuracy, but the elderly required significantly more time.
      Despite equivalent performance, distinct neural networks characterized the
      ceiling. While the young cohort showed subcortical activations, the elderly
      recruited the left inferior frontal gyrus, the left lingual gyrus and the
      precuneus. The learning trajectory of the elderly, the neuroimaging findings
      together with their performance on the Stroop suggest that the young adults
      relied on control processing areas whereas the elderly relied on episodic memory
      circuits, which may reflect resorting to better preserved cognitive resources.
      Finally, the recruitment of visual processing areas by the elderly may reflect
      the impact of the language training method used. 

PMID- 24880753
TI  - Pharmacokinetic and pharmacodynamic interactions between almorexant, a dual
      orexin receptor antagonist, and desipramine.
AB  - Almorexant is a dual orexin receptor antagonist (DORA) with sleep-enabling
      effects in humans. Insomnia is often associated with mental health problems,
      including depression. Hence, potential interactions with antidepressants deserve
      attention. Desipramine was selected as a model drug because it is mainly
      metabolized by CYP2D6, which is inhibited by almorexant in vitro. A single
      center, randomized, placebo-controlled, two-way crossover study in 20 healthy
      male subjects was conducted to evaluate the pharmacokinetic and pharmacodynamic
      interactions between almorexant and desipramine. Almorexant 200mg or matching
      placebo (double-blind) was administered orally once daily in the morning for 10
      days, and a single oral dose of 50mg desipramine (open-label) was administered on
      Day 5. Almorexant increased the exposure to desipramine 3.7-fold, suggesting that
      almorexant is a moderate inhibitor of desipramine metabolism through inhibition
      of CYP2D6. Conversely, desipramine showed no relevant effects on the
      pharmacokinetics of almorexant. Pharmacodynamic evaluations indicated that
      almorexant alone reduced visuomotor coordination, postural stability, and
      alertness, and slightly increased calmness. Desipramine induced a reduction in
      subjective alertness and an increase in pupil/iris ratio. Despite the increase in
      exposure to desipramine, almorexant and desipramine in combination showed the
      same pharmacodynamic profile as almorexant alone, except for prolonging reduced
      alertness and preventing the miotic effect of almorexant. Co-administration also
      prolonged the mydriatic effect of desipramine. Overall, repeated administration
      of almorexant alone or with single-dose desipramine was well tolerated. The lack
      of a relevant interaction with antidepressants, if confirmed for other DORAs,
      would be a key feature for a safer class of hypnotics. 

PMID- 24880755
TI  - Vascularization in 3D bioprinted scaffolds.

PMID- 24880756
TI  - Re: CT imaging of complications of catheter ablation for atrial fibrillation.

PMID- 24880757
TI  - The role of interventional radiology in reducing haemorrhage and hysterectomy
      following caesarean section for morbidly adherent placenta.
AB  - AIM: To report experience of prophylactic occlusion balloon catheters (POBCs) in
      both internal iliac arteries before caesarean section, with or without
      embolization, to preserve the uterus and reduce haemorrhage. METHODS AND
      MATERIALS: Twenty-seven women diagnosed with morbidly adherent placenta (MAP) and
      with suspected placenta percreta underwent POBC placement before caesarean
      section. The balloons were inflated immediately after delivery of the baby. The
      patients' case notes were reviewed retrospectively for histological grading of
      MAP, blood loss, transfusion, requirement of uterine artery embolization (UAE),
      or hysterectomy, radiation dose, and infant or maternal morbidity and mortality.
      RESULTS: MAP was confirmed histologically as percreta in 17, accreta in eight,
      and increta in two women. Mean blood loss was 1.92 l (range 0.5-12 l). Postpartum
      haemorrhage (PPH) occurred in nine patients. Eight were referred for UAE, which
      was successful in six. Immediate peri-partum hysterectomy was performed in one
      patient. Three women in total required hysterectomy, two after recurrent
      haemorrhage after UAE. No foetal morbidity or mortality occurred. No maternal
      mortality occurred. There was one case of iliac artery thrombosis, which resolved
      with conservative therapy. CONCLUSION: POBC, with or without UAE, contributes to
      reduction of blood loss and preservation of the uterus in women with MAP.

PMID- 24880758
TI  - Use of OsiriX in developing a digital radiology teaching library.
AB  - Widespread adoption of digital imaging in clinical practice and for the image
      based examinations of the Royal College of Radiologists has created a desire to
      provide a digital radiology teaching library in many hospital departments around
      the UK. This article describes our experience of using OsiriX software in
      developing digital radiology teaching libraries. 

PMID- 24880760
TI  - [Woman with abdominal distention of 2 months duration].

PMID- 24880759
TI  - Office-based tracheoesophageal puncture: updates in techniques and outcomes.
AB  - PURPOSE: Tracheoesophageal puncture (TEP) is an effective rehabilitation method
      for postlaryngectomy speech and has already been described as a procedure that is
      safely performed in the office. We review our long-term experience with office
      based TEP over the past 7 years in the largest cohort published to date.
      MATERIALS AND METHODS: A retrospective chart review was performed of all patients
      who underwent TEP by a single surgeon from 2005 through 2012, including office
      based and operating room procedures. Indications for the chosen technique (office
      versus operating room) and surgical outcomes were evaluated. RESULTS: Fifty-nine
      patients underwent 72 TEP procedures, with 55 performed in the outpatient setting
      and 17 performed in the operating room, all without complication. The indications
      for performing TEPs in the operating room included 2 primary TEPs, 14 due to
      concomitant procedures requiring general anesthesia, and 1 due to failed attempt
      at office-based TEP. Nineteen patients with prior rotational or free flap
      reconstruction successfully underwent office-based TEP. CONCLUSIONS: TEP in an
      office-based setting with immediate voice prosthesis placement continues to be a
      safe method of voice rehabilitation for postlaryngectomy patients, including
      those who have previously undergone free flap or rotational flap reconstruction.
      Office-based TEP is now our primary approach for postlaryngectomy voice
      rehabilitation.

PMID- 24880761
TI  - [Type 2 diabetes mellitus prevention using a Mediterranean diet and vegetable
      fats: The PREDIMED (PREvencion con DIeta MEDiterranea) study].

PMID- 24880762
TI  - Prevalence of acute cardiac disorders in patients with suspected ST-segment
      elevation myocardial infarction and non-significant coronary artery disease.
AB  - BACKGROUND AND PURPOSE: We aimed to study the prevalence of acute cardiac
      disorders in patients with suspected ST-segment elevation myocardial infarction
      (STEMI) and non-significant coronary artery disease (CAD). METHODS: From January
      to October 2012 we consecutively included patients admitted with suspected STEMI
      and non-significant CAD (coronary artery stenosis diameter <50%). Patients were
      diagnosed with acute cardiac disorder in the presence of elevated cardiac
      biomarkers (troponin T >50ng/l or creatine kinase MB >4MUg/l) or dynamic ECG
      changes (ST-segment changes or T-wave inversion). RESULTS: Of the 871 patients
      admitted with suspected STEMI, 11% (n=95) had non-significant CAD. Of these, 67%
      (n=64) had elevated cardiac biomarkers or dynamic ECG changes and were
      accordingly diagnosed with acute cardiac disorders. In the remaining 33% (n=31)
      of patients, cardiac biomarkers were normal and ECG changes remained stationary.
      CONCLUSIONS: Acute cardiac disorders were diagnosed in two thirds of patients
      with suspected STEMI and non-significant CAD.

PMID- 24880763
TI  - The 24-lead ECG display for enhanced recognition of STEMI-equivalent patterns in
      the 12-lead ECG.
AB  - In a patient with chest pain and suspected acute coronary syndrome, the
      electrocardiogram (ECG) is the only readily available diagnostic tool. It is
      important to maximize its usefulness to detect acute myocardial ischemia that may
      evolve to myocardial infarction unless the patient is treated expediently with
      reperfusion therapy. Since diagnostic guidelines have usually included only ST
      elevation myocardial infarction (STEMI) as the entity that should be diagnosed
      and treated urgently, a patient with coronary occlusion represented on ECG as ST
      depression is likely not to be considered a candidate for receiving immediate
      coronary angiography and coronary intervention. ECG criteria for STEMI detection
      require that ST elevation meet predetermined millivolt thresholds and appear in
      at least two spatially contiguous ECG leads. The typical ECG reader recognizes
      only three contiguous pairs: aVL and I; II and aVF; aVF and III. However, viewing
      the "orderly sequenced" 12-lead ECG display, two more contiguous pairs become
      obvious in the frontal plane: +I and -aVR; -aVR and +II. The 24-lead ECG is a
      display of the standard 12-lead ECG as both the classical positive leads and
      their negative (inverted) counterparts. Leads +V1, +V2, +V3, +V4, +V5, and +V6
      and their inverted counterparts are used to generate a "clock-face display" for
      the transverse plane. Similarly, +aVL, +I, -aVR, +II, +aVF, +III in the frontal
      plane and their inverted counterparts are used to generate a clock-face display
      for the frontal plane. Optimum results, 78% sensitivity and 93% specificity, were
      obtained using the following 19 ECG leads: frontal plane: +aVR, -III, +aVL, +I, 
      aVR, +II, +aVF, +III, -aVL; transverse plane: +V1, +V2, +V3, +V4, +V5, +V6, -V1, 
      V2, -V3.

PMID- 24880764
TI  - Neuroendoscopy and pineal tumors: A review of the literature and our
      considerations regarding its utility.
AB  - Endoscopy has entered into the armamentarium of pineal and pineal region tumor
      treatment. The technique permits not only to control hydrocephalus but also to
      obtain tissue samples for histological diagnosis. In this paper, we explain the
      utility of endoscopy for the treatment of pineal tumors and as well as report
      some personal considerations regarding this topic. 

PMID- 24880765
TI  - Ultrasound pretreatment for enhanced biogas production from olive mill
      wastewater.
AB  - This study investigates applicability of low frequency ultrasound technology to
      olive mill wastewaters (OMWs) as a pretreatment step prior to anaerobic batch
      reactors to improve biogas production and methane yield. OMWs originating from
      three phase processes are characterized with high organic content and complex
      nature. The treatment of the wastewater is problematic and alternative treatment
      options should be investigated. In the first part of the study, OMW samples were
      subjected to ultrasound at a frequency of 20kHz with applied powers varying
      between 50 and 100W under temperature controlled conditions for different time
      periods in order to determine the most effective sonication conditions. The level
      of organic matter solubilization at ultrasound experiments was assessed by
      calculating the ratio of soluble chemical oxygen demand/total chemical oxygen
      demand (SCOD/TCOD). The results revealed that the optimum ultrasonic condition
      for diluted OMW is 20kHz, 0.4W/mL for 10min. The application of ultrasound to OMW
      increased SCOD/TCOD ratio from 0.59 to 0.79. Statistical analysis (Friedman's
      tests) show that ultrasound was significantly effective on diluted OMW (p<0.05)
      in terms of SCOD parameter, but not for raw OMW (p>0.05). For raw OMW, this
      increase has been found to be limited due to high concentration of suspended
      solids (SS). In the second part of the study, biogas and methane production rates
      of anaerobic batch reactor fed with the ultrasound pretreated OMW samples were
      compared with the results of control reactor fed with untreated OMW in order to
      determine the effect of sonication. A nonparametric statistical procedure, Mann
      Whitney U test, was used to compare biogas and methane production from anaerobic
      batch reactors for control and ultrasound pretreated samples. Results showed that
      application of low frequency ultrasound to OMW significantly improved both biogas
      and methane production in anaerobic batch reactor fed with the wastewater
      (p<0.05). Anaerobic batch reactor fed with ultrasound pretreated diluted OMW
      produced approximately 20% more biogas and methane compared with the untreated
      one (control reactor). The overall results indicated that low frequency
      ultrasound pretreatment increased soluble COD in OMW and subsequently biogas
      production. 

PMID- 24880766
TI  - Effect of ultrasound in the free radical polymerization of acrylonitrile under a
      new multi-site phase-transfer catalyst - a kinetic study.
AB  - The kinetics of polymerization of acrylonitrile (AN) was carried out under
      heterogeneous condition using a new multi-site phase-transfer catalyst (MPTC),
      viz., N,N'-dihexyl-4,4'-bipyridinium dibromide in the presence of water soluble
      initiator, potassium peroxydisulphate (PDS) under chlorobenzene/water two phase
      system assisted by ultrasound irradiation at constant temperature 60+1 degrees C
      under nitrogen atmosphere. The rate of polymerization increases with an
      increasing the concentrations of AN, MPTC and PDS. The order with respect to
      [AN], [MPTC], and [PDS] were found to be 1.01, 1.03 and 0.52, respectively. Based
      on the observed results a suitable mechanism has been proposed to account for the
      experimental observations followed by a discussion on its significance. 

PMID- 24880767
TI  - Stratified medicine approaches for the treatment of musculoskeletal disorders.
AB  - Stratified medicine approaches for the treatment of musculoskeletal disorders
      offer opportunities to effectively target interventions to those individuals who
      will gain most benefit from them and minimise adverse side effects. Such
      approaches have been the 'holy grail' of a variety of research fields spanning
      epidemiological, (epi)genetic, transcriptomic, proteomic and imaging biomarkers
      that predict disease diagnosis, prognosis or response to treatment. In this
      review, we highlight the successes and opportunities for stratified medicine
      approaches across a range of musculoskeletal disorders, with a focus on genetic
      risk factors, since these are the most stable across the lifetime of each
      individual. 

PMID- 24880774
TI  - Towards new methods for the determination of dose limiting toxicities and the
      assessment of the recommended dose for further studies of molecularly targeted
      agents--dose-Limiting Toxicity and Toxicity Assessment Recommendation Group for
      Early Trials of Targeted therapies, an European Organisation for Research and
      Treatment of Cancer-led study.
AB  - INTRODUCTION: Traditional dose-limiting toxicity (DLT) definition, which uses
      grade (G) 3-4 toxicity data from cycle 1 (C1) only, may not be appropriate for
      molecularly targeted agents (MTAs) of prolonged administration, for which late or
      lower grade toxicities also deserve attention. PATIENTS AND METHODS: In
      collaboration with pharmaceutical companies and academia, an European
      Organisation for Research and Treatment of Cancer (EORTC)-led initiative, Dose
      Limiting Toxicity and Toxicity Assessment Recommendation Group for Early Trials
      of Targeted therapies (DLT-TARGETT), collected data from completed phase 1 trials
      evaluating MTAs as monotherapy. All toxicities at least possibly related to the
      study drugs that occurred during C1-6, their type, grade (CTCAEv3.0), and
      duration as well as patients' relative dose-intensity (RDI), were recorded.
      RESULTS: The 54 eligible trials enrolled 2084 evaluable adult patients with solid
      tumours between 1999 and 2013, and evaluated small molecules (40), antibodies
      (seven), recombinant peptides (five) and antisense oligodeoxynucleotides (two). A
      maximum tolerated dose was set in 43 trials. Fifteen percent of the patients
      received <75% of the intended RDI in C1, but only 9.1% of them presented protocol
      defined DLTs. After C1, 16-19% of patients received <75% of the intended RDI. A
      similar proportion of G ? 3 toxicities was recorded in C1 and after C1 (936 and
      1087 toxicities, respectively), with the first G?3 toxicity occurring after C1 in
      18.6% of patients. CONCLUSION: Although protocol-defined DLT period is
      traditionally limited to C1, almost 20% of patients present significant
      reductions in RDI at any time in phase 1 trials of MTAs. Recommended phase 2 dose
      assessment should incorporate all available information from any cycle (notably
      lower grade toxicities leading to such RDI decrease), and be based on achieving
      >75% RDI.

PMID- 24880775
TI  - Multifunctional exopolysaccharides from Pseudomonas aeruginosa PF23 involved in
      plant growth stimulation, biocontrol and stress amelioration in sunflower under
      saline conditions.
AB  - Isolate PF23 selected from among 110 fluorescent pseudomonads, identified as
      Pseudomonas aeruginosa, displayed salinity tolerance and exopolysaccharides (EPS)
      production up to 2,000 mM NaCl concentration. EPS-defective mutant PF23(EPS-) of
      the isolate showed 86 % reduction in EPS production in comparison with wild
      strain. Defect in EPS production brought loss in salt tolerance capability.
      Purified EPS obtained from PF23 displayed multiple roles. At low concentration
      EPS functioned as biocontrol agent, at high concentration EPS behaved as
      osmoprotective or stress ameliorating metabolite and when introduced in saline
      soil, served as a plant growth promotor along with seed biopriming agent. Both in
      planta and in vivo studies were performed taking sunflower as a test crop and it
      was observed that PF23 showed plant growth promotion and significant biocontrol
      potential against dreadful phytopathogen Macrophomina phaseolina (under saline
      conditions). The mutant PF23(EPS-) was ineffective under saline conditions both
      in growth enhancement as well as in disease suppression. The study reports a
      potent strain, Pseudomonas aeruginosa PF23, capable of enhancing production of
      sunflower crop in semiarid regions and minimizing the incidence of charcoal rot
      disease in sunflower. 

PMID- 24880776
TI  - Spread of Mycobacterium avium subsp. paratuberculosis through soil and grass on a
      mouflon (Ovis aries) pasture.
AB  - The aims of this study were to describe spatial contamination of the environment
      on a mouflon pasture, as well as to assess the contamination of grass and roots
      after surface contamination and in depth contamination with feces and buried
      tissues from animals infected with Mycobacterium avium subsp. paratuberculosis
      (M. a. paratuberculosis). Samples of soil, roots, and aerial parts of plants were
      collected from different locations inside the mouflon pasture, and one control
      sample site was chosen outside the area where the animals are living. M. a.
      paratuberculosis DNA was present in all the examined sites and was more often
      detected in roots than in soil. DNA was detected at up to 80 cm of depth and was
      spatially more widespread than the initial hypothesis of M. a. paratuberculosis
      leaching vertically into deeper layers of soil. This study broadens our knowledge
      of the spread and persistence of M. a. paratuberculosis in an environment with
      highly infected animals. 

PMID- 24880777
TI  - Clinical Commentary: therapist supervised clinic-based therapy versus instruction
      in a home program following distal radius fracture: a systematic review.

PMID- 24880778
TI  - Immediate changes in neck pain intensity and widespread pressure pain sensitivity
      in patients with bilateral chronic mechanical neck pain: a randomized controlled
      trial of thoracic thrust manipulation vs non-thrust mobilization.
AB  - OBJECTIVE: The purpose of this study was to compare the effects of thoracic
      thrust manipulation vs thoracic non-thrust mobilization in patients with
      bilateral chronic mechanical neck pain on pressure pain sensitivity and neck pain
      intensity. METHODS: Fifty-two patients (58% were female) were randomly assigned
      to a thoracic spine thrust manipulation group or of thoracic non-thrust
      mobilization group. Pressure pain thresholds (PPTs) over C5-C6 zygapophyseal
      joint, second metacarpal, and tibialis anterior muscle and neck pain intensity
      (11-point Numerical Pain Rate Scale) were collected at baseline and 10 minutes
      after the intervention by an assessor blinded to group allocation. Mixed-model
      analyses of variance (ANOVAs) were used to examine the effects of the treatment
      on each outcome. The primary analysis was the group * time interaction. RESULTS:
      No significant interactions were found with the mixed-model ANOVAs for any PPT
      (C5-C6: P>.252; second metacarpal: P>.452; tibialis anterior: P>.273): both
      groups exhibited similar increases in PPT (all, P<.01), but within-group and
      between-group effect sizes were small (standardized mean score difference
      [SMD]<0.22). The ANOVA found that patients receiving thoracic spine thrust
      manipulation experienced a greater decrease in neck pain (between-group mean
      difference: 1.4; 95% confidence interval, 0.8-2.1) than did those receiving
      thoracic spine non-thrust mobilization (P<.001). Within-group effect sizes were
      large for both groups (SMD>2.1), and between-group effect size was also large
      (SMD = 1.3) in favor of the manipulative group. CONCLUSIONS: The results of this
      randomized clinical trial suggest that thoracic thrust manipulation and non
      thrust mobilization induce similar changes in widespread PPT in individuals with
      mechanical neck pain; however, the changes were clinically small. We also found
      that thoracic thrust manipulation was more effective than thoracic non-thrust
      mobilization for decreasing intensity of neck pain for patients with bilateral
      chronic mechanical neck pain.

PMID- 24880780
TI  - Different replication protein A complexes of Arabidopsis thaliana have different
      DNA-binding properties as a function of heterotrimer composition.
AB  - The heterotrimeric RPA (replication protein A) protein complex has single
      stranded DNA-binding functions that are important for all DNA processing pathways
      in eukaryotic cells. In Arabidopsis thaliana, which has five homologs of the RPA1
      subunit and two homologs each of RPA2 and RPA3, in theory 20 RPA complexes could
      form. Using Escherichia coli as a heterologous expression system and analysing
      the results of the co-purification of the different subunits, we conclude that
      AtRPA1a interacts with the AtRPA2b subunit, and AtRPA1b interacts with AtRPA2a.
      Additionally either AtRPA3a or AtRPA3b is part of the complexes. As shown by
      electrophoretic mobility shift assays, all of the purified AtRPA complexes bind
      single-stranded DNA, but differences in DNA binding, especially with respect to
      modified DNA, could be revealed for all four of the analyzed RPA complexes. Thus,
      the RPA3 subunits influence the DNA-binding properties of the complexes
      differently despite their high degree of similarity of 82%. The data support the
      idea that in plants a subfunctionalization of RPA homologs has occurred and that
      different complexes act preferentially in different pathways. 

PMID- 24880779
TI  - Auxin sensitivities of all Arabidopsis Aux/IAAs for degradation in the presence
      of every TIR1/AFB.
AB  - Auxin plays a key role in regulation of almost all processes of plant growth and
      development. Different physiological processes are regulated by different ranges
      of auxin concentrations; however, the underlying mechanisms creating these
      differences are largely unknown. The first step of auxin signaling is auxin
      dependent interaction of an auxin receptor with transcriptional co-repressors
      (Aux/IAA), which leads to Aux/IAA degradation. Arabidopsis has six homologous
      auxin receptors (TIR1 and five AFBs), 29 Aux/IAA proteins and two types of active
      auxins, IAA and phenylacetic acid (PAA). Therefore, a large number of possible
      combinations between these three factors may contribute to the creation of
      complex auxin responses. Using a yeast heterologous reconstitution system, we
      investigated auxin-dependent degradation of all Arabidopsis Aux/IAAs in
      combination with every TIR or AFB receptor component. We found that TIR1 and AFB2
      were effective in mediating Aux/IAA degradation. We confirmed that the Aux/IAA
      domain II, which binds TIR1, is essential for degradation. IAA and other natural
      auxins, 4-chloroindole-3-acetic acid (4-Cl-IAA) and PAA, induced Aux/IAA
      degradation; and IAA and 4-Cl-IAA had higher activity than PAA. Effective auxin
      concentrations for Aux/IAA degradation depended on both Aux/IAAs and TIR1 or AFB2
      receptors, which is consistent with the Aux/IAA-TIR1/AFB co-receptor concept. 

PMID- 24880781
TI  - M-mode, two-dimensional and Doppler echocardiographic findings in 40 healthy
      domestic pet rabbits.
AB  - OBJECTIVES: The aim of the study was to report normal two-dimensional, M-mode,
      and Doppler echocardiographic findings from a large cohort of healthy, manually
      restrained, adult pet rabbits. ANIMALS AND METHODS: Forty healthy pet rabbits [22
      Dwarf Lops (DL), 14 French Lops (FL) and 4 Alaskan (AL)] underwent a full
      physical examination and conscious two-dimensional, M-mode, and Doppler
      echocardiography. RESULTS: The median age of the rabbits was 21.5 months, the
      median weight was 2.9 kg (DL: 2.4 kg, AL: 4.35 kg, FL: 6.0 kg). Echocardiography
      with ECG monitoring was feasible in all rabbits. Left atrial and ventricular
      dimensions were significantly larger in FL as compared to DL; overall, a positive
      correlation with weight was present. No significant differences between breeds
      were identified for flow velocities. Trace regurgitation was detected at the
      aortic valve in 7/40 (17.5%) rabbits, at the tricuspid valve in 5/40 (12.5%) and
      at the pulmonic valve in 1/40 (2.5%) rabbits. Mitral inflow E and A waves were
      summated in 60% of cases. CONCLUSIONS: The results of this study can be used as
      echocardiographic values in FL and DL for comparison with clinical cases, and may
      also be applicable for other breeds of similar sizes. Breed specific values
      should be used when measuring left atrial and ventricular sizes. However, no
      breed or size differences were found for the rest of the echocardiographic
      parameters, which may therefore be applicable for the general pet rabbit
      population.

PMID- 24880782
TI  - Campylobacter jejuni cell lysates differently target mitochondria and lysosomes
      on HeLa cells.
AB  - Campylobacter jejuni is the most common cause of bacterial gastroenteritis in
      humans. The synthesis of cytolethal distending toxin appears essential in the
      infection process. In this work we evaluated the sequence of lethal events in
      HeLa cells exposed to cell lysates of two distinct strains, C. jejuni ATCC 33291
      and C. jejuni ISS3. C. jejuni cell lysates (CCLys) were added to HeLa cell
      monolayers which were analysed to detect DNA content, death features, bcl-2 and
      p53 status, mitochondria/lysosomes network and finally, CD54 and CD59
      alterations, compared to cell lysates of C. jejuni 11168H cdtA mutant. We found
      mitochondria and lysosomes differently targeted by these bacterial lysates.
      Death, consistent with apoptosis for C. jejuni ATCC 33291 lysate, occurred in a
      slow way (>48 h); concomitantly HeLa cells increase their endolysosomal
      compartment, as a consequence of toxin internalization besides a simultaneous and
      partial lysosomal destabilization. C. jejuni CCLys induces death in HeLa cells
      mainly via a caspase-dependent mechanism although a p53 lysosomal pathway (also
      caspase-independent) seems to appear in addition. In C. jejuni ISS3-treated
      cells, the p53-mediated oxidative degradation of mitochondrial components seems
      to be lost, inducing the deepest lysosomal alterations. Furthermore, CD59
      considerably decreases, suggesting both a degradation or internalisation pathway.
      CCLys-treated HeLa cells increase CD54 expression on their surface, because of
      the action of lysate as its double feature of toxin and bacterial peptide. In
      conclusion, we revealed that C. jejuni CCLys-treated HeLa cells displayed
      different features, depending on the particular strain.

PMID- 24880783
TI  - Enantioselective toxicities of chiral ionic liquids 1-alkyl-3-methylimidazolium
      lactate to aquatic algae.
AB  - With the wide application of chiral ionic liquids (CILs) as green solvents, their
      threats to the aquatic environment cannot be ignored. Thus, risk assessment and
      the prospective design of inherently safe CILs have become more urgent. However,
      whether enantioselectivity is a feature of the aquatic toxicity of CILs is poorly
      understood. Herein, we describe the first investigation into the ecotoxicities of
      CILs toward green algae Scenedesmus obliquus and Euglena gracilis. A series of
      methylimidazolium lactic ionic liquids, which cation parts with different alkyl
      chains and anion part is enantiomers of lactate, are used as representative CILs.
      The results of S. obliquus showed that the EC50 value of L-(+)-1-ethyl-3
      methylimidazolium lactate (L-(+)-EMIM L) was more than 5000 MUM, while the EC50
      value of D-(-)-1-ethyl-3-methylimidazolium lactate (D-(-)-EMIM L) was 2255.21
      MUM. Such a distinct difference indicates the enantioselective toxicity of CILs
      to algae. This enantioselectivity initially persisted with increasing carbon
      chain length, but no longer exhibited when with greater carbon chain lengths, due
      to changes in the toxicity weightings of the cation parts. Further research
      showed that the enantioselective effects of CILs resulted from the differences in
      the production of reactive oxygen species, the damage to cell membrane integrity
      and cell wall after exposure to CILs. Results from this study showed that
      monitoring for the racemate CILs will give an inadequate or misleading
      environmental risk assessment. Thus, we should improve our ability to predict
      their effects in natural environments. In the meantime, non-selective use of CILs
      will do harm to aquatic organisms. Therefore, to minimize their potential for
      environmental impact, the enantioselective toxicities of CILs with short alkyl
      chains should be taken into consideration.

PMID- 24880784
TI  - Biodynamic modelling of the bioaccumulation of trace metals (Ag, As and Zn) by an
      infaunal estuarine invertebrate, the clam Scrobicularia plana.
AB  - Biodynamic modelling was used to investigate the uptake and accumulation of three
      trace metals (Ag, As, Zn) by the deposit feeding estuarine bivalve mollusc
      Scrobicularia plana. Radioactive labelling techniques were used to quantify the
      rates of trace metal uptake (and subsequent elimination) from water and sediment
      diet. The uptake rate constant from solution (+/-SE) was greatest for Ag (3.954+/
      0.375 l g(-1) d(-1)) followed by As (0.807+/-0.129 l g(-1) d(-1)) and Zn (0.103+/
      0.016 l g(-1) d(-1)). Assimilation efficiencies from ingested sediment were
      40.2+/-1.3% (Ag), 31.7+/-1.0% (Zn) and 25.3+/-0.9% (As). Efflux rate constants
      after exposure to metals in the solution or sediment fell in the range of 0.014
      0.060 d(-1). By incorporating these physiological parameters into biodynamic
      models, our results showed that dissolved metal is the predominant source of
      accumulated Ag, As and Zn in S. plana, accounting for 66-99%, 50-97% and 52-98%
      of total accumulation of Ag, As and Zn, respectively, under different field
      exposure conditions. In general, model-predicted steady state concentrations of
      Ag, As and Zn matched well with those observed in clams collected in SW England
      estuaries. Our findings highlight the potential of biodynamic modelling to
      predict Ag, As and Zn accumulation in S. plana, taking into account specific
      dissolved and sediment concentrations of the metals at a particular field site,
      together with local water and sediment geochemistries.

PMID- 24880785
TI  - N-Acetylcysteine boosts xenobiotic detoxification in shellfish.
AB  - Water pollution represents a threat of increasing importance to human health.
      Bivalve mollusks are filter-feeding organisms that can accumulate chemical and
      microbiological contaminants in their tissues from very low concentrations in the
      water or sediments. Consumption of contaminated shellfish is one of the main
      causes of seafood poisoning. Thus, marine bivalves are normally depurated in
      sterilized seawater for 48 h to allow the removal of bacteria. However, this
      depuration time might be insufficient to eliminate chemical contaminants from
      their tissues. We have developed a novel technology that accelerates up to
      fourfold the excretion rate of xenobiotics in bivalves by treatment with the
      antioxidant and glutathione (GSH) pro-drug N-acetylcysteine (NAC) during the
      depuration period. NAC improved dose-dependently the detoxification of the
      organophosphate (OP) pesticide fenitrothion in the mussel Mytilus
      galloprovincialis, diminishing its levels up to nearly a hundred fold compared to
      conventional depuration, by enhancing the glutathione S-transferase (GST)
      activity and inducing the GSH anabolism (GSH synthesis and reduction by
      glutathione reductase). Notably, this induction in GSH anabolism and GST activity
      was also observed in uncontaminated bivalves treated with NAC. As the GSH pathway
      is involved in the detoxification of many pollutants and biotoxins from harmful
      algal blooms, we validated this proof of principle in king scallops (Pecten
      maximus) that naturally accumulated the amnesic shellfish poisoning (ASP) toxin
      domoic acid. We illustrate here a method that enhances the elimination of organic
      contaminants in shellfish, opening new avenues of depuration of marine organisms.

PMID- 24880786
TI  - Chronic nickel bioaccumulation and sub-cellular fractionation in two freshwater
      teleosts, the round goby and the rainbow trout, exposed simultaneously to
      waterborne and dietborne nickel.
AB  - Rainbow trout and round goby were exposed for 30 days to waterborne and dietary
      Ni in combination at two waterborne concentration ranges (6.2-12 MUmol/L, 68-86
      MUmol/L), the lower of which is typical of contaminated environments. The prey
      (black worms; Lumbriculus variegatus) were exposed for 48 h in the effluent of
      the fish exposure tanks before being fed to the fish (ration=2% body weight/day).
      Ni in gills, gut, and prey was fractionated into biologically inactive metal
      [BIM=metal-rich granules (MRG) and metallothionein-like proteins (MT)] and
      biologically active metal [BAM=organelles (ORG) and heat-denaturable proteins
      (HDP)]. Gobies were more sensitive than trout to chronic Ni exposure. Possibly,
      this greater sensitivity may have been due to the goby's pre-exposure to
      pollutants at their collection site, as evidenced by ~2-fold greater initial Ni
      concentrations in both gills and gut relative to trout. However, this was
      followed by ~2-16* larger bioaccumulation in both the gills and the gut during
      the experimental exposure. On a subcellular level, ~3-40* more Ni was associated
      with the BAM fraction of goby in comparison to trout. Comparison of the
      fractional distribution of Ni in the prey versus the gut tissue of the predators
      suggested that round goby were more efficient than rainbow trout in detoxifying
      Ni taken up from the diet. Assessing sub-cellular distribution of Ni in the gills
      and gut of two fish of different habitat and lifestyles revealed two different
      strategies of Ni bioaccumulation and sub-cellular distribution. On the one hand,
      trout exhibited an ability to regulate gill Ni bioaccumulation and maintain the
      majority of the Ni in the MT fraction of the BIM. In contrast goby exhibited
      large Ni spillovers to both the HDP and ORG fractions of the BAM in the gill.
      However, the same trend was not observed in the gut, where the potential
      acclimation of goby to pollutants from their collection site may have aided their
      ability to regulate Ni spillover to the BAM more so than in trout. Overall,
      chronic mortality observed in goby may be associated more with Ni bioaccumulation
      in gills than in gut; the former at either 4-d or 30-d was predictive of chronic
      Ni toxicity. BIM and BAM fractions of the goby gills were equally predictive of
      chronic (30-d) mortality. However, critical body residue (CBR50) values of the
      BIM fraction were ~2-4* greater than CBR50 values of the BAM fraction, suggesting
      that goby are more sensitive to Ni bioaccumulation in the BAM fraction. There was
      insufficient mortality in trout to assess whether Ni bioaccumulation was
      predictive of chronic mortality.

PMID- 24880788
TI  - Distribution, prevalence and host specificity of avian malaria parasites across
      the breeding range of the migratory lark sparrow (Chondestes grammacus).
AB  - The lark sparrow (Chondestes grammacus) is a ground-nesting passerine that breeds
      across much of the central North American steppe and sand barrens. Through
      genotyping and sequencing of avian malaria parasites we examined levels of
      malaria prevalence and determined the distribution of Haemoproteus and Plasmodium
      lineages across the breeding range of the lark sparrow. Analysis of 365 birds
      collected from five breeding locations revealed relatively high levels of malaria
      prevalence in adults (80 %) and juveniles (46 %), with infections being primarily
      of Haemoproteus (91 % of sequenced samples). Levels of genetic diversity and
      genetic structure of malaria parasites with respect to the avian host populations
      revealed distinct patterns for Haemoproteus and Plasmodium, most likely as a
      result of their distinct life histories, host specificity, and transmission
      vectors. With the exception of one common Haemoproteus haplotype detected in all
      populations, all other haplotypes were either population-specific or shared by
      two to three populations. A hierarchical analysis of molecular variance of
      Haemoproteus sequences revealed that 15-18 % of the genetic variation can be
      explained by differences among host populations/locations (p < 0.001). In
      contrast to the regional patterns of genetic differentiation detected for the
      lark sparrow populations, Haemoproteus parasites showed high levels of population
      specific variation and no significant differences among regions, which suggests
      that the population dynamics of the parasites may be driven by evolutionary
      processes operating at small spatial scales (e.g., at the level of host
      populations). These results highlight the potential effects of host population
      structure on the demographic and evolutionary dynamics of parasites.

PMID- 24880789
TI  - Interpersonal skills development in Generation Y student nurses: a literature
      review.
AB  - BACKGROUND: Student nurses require training in the development of the
      interpersonal skills that are required for therapeutic nurse-patient
      relationships. This training should be provided within the basic education of
      nurses in a higher education institution. As the birth years of Generation Y
      range from the early 1980s to the late 1990s this generation is of the age group
      that enrols in higher education institutions. The unique learning needs of this
      generation necessitate a review of teaching strategies used in the development of
      interpersonal skills. OBJECTIVES: The aim of this study is to present a
      literature review on the significance and development of interpersonal skills in
      Generation Y nursing students through nursing education. METHODOLOGY: Literature
      searches were conducted on databases-with the use of Cumulative Index of Nursing
      and Allied Health (CINAHL), Clinical key, PubMed and Google Scholar-using
      specific keywords and a timeframe of 2005 to 2013. All relevant articles were
      read critically. FINDINGS: Interpersonal skills are at the core of the nurse
      patient relationship. Meaningful interaction is recognised in Swanson's theory of
      "informed caring". Debates, case studies, role-playing, storytelling, journaling,
      simulations and web page links to audio and video clips are some of the teaching
      strategies which can develop the interpersonal skills needed for meaningful
      interactions. CONCLUSION: Teaching strategies embedded in the deconstruction
      pedagogies stimulate critical, analytical thinking through methods which
      complement the unique learning styles of Generation Y learners.

PMID- 24880787
TI  - The physiology of the pedunculopontine nucleus: implications for deep brain
      stimulation.
AB  - This brief review resolves a number of persistent conflicts regarding the
      location and characteristics of the mesencephalic locomotor region, which has in
      the past been described as not locomotion-specific and is more likely the
      pedunculopontine nucleus (PPN). The parameters of stimulation used to elicit
      changes in posture and locomotion we now know are ideally suited to match the
      intrinsic membrane properties of PPN neurons. The physiology of these cells is
      important not only because it is a major element of the reticular activating
      system, but also because it is a novel target for the treatment of gait and
      postural deficits in Parkinson's disease (PD). The discussion explains many of
      the effects reported following deep brain stimulation (DBS) of the PPN by
      different groups and provides guidelines for the determination of long-term
      assessment and effects of PPN DBS. A greater understanding of the physiology of
      the target nuclei within the brainstem and basal ganglia, amassed over the past
      decades, has enabled increasingly better patient outcomes from DBS for movement
      disorders. Despite these improvements, there remains a great opportunity for
      further understanding of the mechanisms through which DBS has its effects and for
      further development of appropriate technology to effect these treatments. We
      review the scientific basis for one of the newest targets, the PPN, in the
      treatment of PD and other movement disorders, and address the needs for further
      investigation.

PMID- 24880790
TI  - Characterization of the Aspergillus fumigatus chitosanase CsnB and evaluation of
      its potential use in serological diagnostics.
AB  - Aspergillus fumigatus is currently the major air-borne fungal pathogen as its
      asexual spores are distributed through the air. In severely immunocompromised
      patients, inhalation of these conidia can result in life-threatening infections.
      Invasive Aspergillosis, a major Aspergillus-associated disease, is associated
      with a high mortality reflecting short-comings in diagnostics and therapy.
      Current diagnostics largely rely on the serological detection of the
      galactomannan antigen. Detection of circulating antibodies is an alternative
      approach. In this study, we have characterized the chitosanase CsnB, a protein
      that was previously shown to be a major secreted A. fumigatus antigen and
      therefore a potential target for antibody-based diagnostics. To analyze the
      biological function of CsnB we have deleted the csnB gene and generated CsnB
      specific antibodies. We found that A. fumigatus is able to grow on chitosan in a
      CsnB-dependent manner. During growth on chitosan elevated levels of CsnB are
      found in the supernatants indicating that chitosan triggers enhanced CsnB
      production. Unexpectedly we have found a similar activity for tartrate. Using
      recombinant proteins we analyzed antibody responses in patients at risk to
      develop invasive aspergillosis. We focussed this study on two antigens: CsnB and
      for comparison mitogillin, a secreted A. fumigatus ribotoxin. IgG responses were
      found to both proteins, but elevated antibody levels to CsnB and/or mitogillin
      showed no correlation to the results of the galactomannan antigen assay or
      clinical signs that are characteristic for fungal infections. 

PMID- 24880791
TI  - Cross-sectional relationships between dyadic coping and anxiety, depression, and
      relationship satisfaction for patients with prostate cancer and their spouses.
AB  - OBJECTIVE: Dyadic coping has an impact on couples' adjustment to breast cancer;
      however, there is limited evidence regarding whether dyadic coping influences
      couples' adjustment to other types of cancer. The objective of this analysis was
      to further our knowledge of the relationships between dyadic coping, anxiety,
      depression, and relationship satisfaction among couples facing prostate cancer.
      METHODS: Forty-two men recently diagnosed with prostate cancer recruited from
      urology clinics and their spouses completed measures of dyadic coping, anxiety,
      depression, and relationship satisfaction. The Actor-Partner Interdependence
      Model was used to examine the relationships among these concepts. RESULTS:
      Relationship satisfaction was significantly associated with patients' and wives'
      use of positive and negative dyadic coping, and their partners' use of these
      strategies. Although patients' and wives' use of supportive dyadic coping was not
      associated with their anxiety and depression, their partner's use of this
      strategy was associated with anxiety and depression. Only husbands' and wives'
      perceptions of their partner's negative dyadic coping was associated with anxiety
      and depression. CONCLUSIONS/PRACTICE IMPLICATIONS: Couples respond to a prostate
      cancer diagnosis as an interactional system. Future research should focus on
      tailoring couple-based interventions such that patients and spouses are equipped
      to provide the specific support their partners need.

PMID- 24880793
TI  - Prevention of combat-related infections: antimicrobial therapy in battlefield and
      barrier measures in French military medical treatment facilities.
AB  - Infection is a major complication associated with combat-related injuries. Beside
      immobilization, wound irrigation, surgical debridement and delayed coverage, post
      injury antimicrobials contribute to reduce combat-related infections,
      particularly those caused by bacteria of the early contamination flora. In modern
      warfare, bacteria involved in combat-related infections are mainly Gram-negative
      bacteria belonging to the late contamination flora. These bacteria are frequently
      resistant or multiresistant to antibiotics and spread through the deployed chain
      of care. This article exposes the principles of war wounds antimicrobial
      prophylaxis recommended in the French Armed Forces and highlights the need for
      high compliance to hygiene standard precautions, adapted contact precautions and
      judicious use of antibiotics in French deployed military medical treatment
      facilities (MTF). 

PMID- 24880792
TI  - Idiopathic pleuroparenchymal fibroelastosis is characterized by an elevated serum
      level of surfactant protein-D, but Not Krebs von den Lungen-6.
AB  - PURPOSE: Idiopathic pleuroparenchymal fibroelastosis (IPPFE) is a recently
      reported rare disease entity characterized by fibrotic thickening of the pleural
      and subpleural parenchyma predominantly in the upper lobes in idiopathic
      interstitial pneumonias (IIPs). Because the clinical features of this rare
      disease are not fully elucidated, we examined the clinical characteristics of
      IPPFE, especially for serum interstitial biomarkers, surfactant protein-D (SP-D),
      and Krebs von den Lungen-6 (KL-6). METHODS AND RESULTS: Four consecutive cases of
      IPPFE who fulfilled the diagnostic criteria were studied. All cases were more
      than 60 years of age, and were classified as underweight by body mass index. A
      severe restrictive ventilatory defect was found in all cases on admission. High
      resolution computed tomography showed intense pleural thickening associated with
      fibrosis predominant in upper lobes. Histopathological findings were also
      confirmed in three out of four cases. Interestingly, the serum level of SP-D was
      markedly elevated in all cases, while KL-6 was within normal range in three out
      of four cases. As compared with major IIPs such as idiopathic pulmonary fibrosis
      and fibrotic nonspecific interstitial pneumonia, IPPFE significantly showed
      higher frequency of cases with a unique pattern of serum biomarkers, which is
      characterized by an elevated level of SP-D with a normal range of KL-6.
      CONCLUSIONS: In IPPFE, SP-D might tend to be elevated, while KL-6 was within a
      normal range. Further study is required to determine the pathogenesis and
      clinical significance of the elevated SP-D in IPPFE.

PMID- 24880794
TI  - Cephalopod culture: current status of main biological models and research
      priorities.
AB  - A recent revival in using cephalopods as experimental animals has rekindled
      interest in their biology and life cycles, information with direct applications
      also in the rapidly growing ornamental aquarium species trade and in commercial
      aquaculture production for human consumption. Cephalopods have high rates of
      growth and food conversion, which for aquaculture translates into short culture
      cycles, high ratios of production to biomass and high cost-effectiveness.
      However, at present, only small-scale culture is possible and only for a few
      species: the cuttlefish Sepia officinalis, the loliginid squid Sepioteuthis
      lessoniana and the octopuses Octopus maya and O. vulgaris. These four species are
      the focus of this chapter, the aims of which are as follows: (1) to provide an
      overview of the culture requirements of cephalopods, (2) to highlight the
      physical and nutritional requirements at each phase of the life cycle regarded as
      essential for successful full-scale culture and (3) to identify current
      limitations and the topics on which further research is required. Knowledge of
      cephalopod culture methods is advanced, but commercialization is still
      constrained by the highly selective feeding habits of cephalopods and their
      requirement for large quantities of high-quality (preferably live) feed,
      particularly in the early stages of development. Future research should focus on
      problems related to the consistent production of viable numbers of juveniles, the
      resolution of which requires a better understanding of nutrition at all phases of
      the life cycle and better broodstock management, particularly regarding
      developments in genetic selection, control of reproduction and quality of eggs
      and offspring. 

PMID- 24880795
TI  - Environmental effects on cephalopod population dynamics: implications for
      management of fisheries.
AB  - Cephalopods are a relatively small class of molluscs (~800 species), but they
      support some large industrial scale fisheries and numerous small-scale, local,
      artisanal fisheries. For several decades, landings of cephalopods globally have
      grown against a background of total finfish landings levelling off and then
      declining. There is now evidence that in recent years, growth in cephalopod
      landings has declined. The commercially exploited cephalopod species are fast
      growing, short-lived ecological opportunists. Annual variability in abundance is
      strongly influenced by environmental variability, but the underlying causes of
      the links between environment and population dynamics are poorly understood.
      Stock assessment models have recently been developed that incorporate
      environmental processes that drive variability in recruitment, distribution and
      migration patterns. These models can be expected to improve as more, and better,
      data are obtained on environmental effects and as techniques for stock
      identification improve. A key element of future progress will be improved
      understanding of trophic dynamics at all phases in the cephalopod life cycle. In
      the meantime, there is no routine stock assessment in many targeted fisheries or
      in the numerous by-catch fisheries for cephalopods. There is a particular need
      for a precautionary approach in these cases. Assessment in many fisheries is
      complicated because cephalopods are ecological opportunists and stocks appear to
      have benefited from the reduction of key predator by overexploitation. Because of
      the complexities involved, ecosystem-based fisheries management integrating
      social, economic and ecological considerations is desirable for cephalopod
      fisheries. An ecological approach to management is routine in many fisheries, but
      to be effective, good scientific understanding of the relationships between the
      environment, trophic dynamics and population dynamics is essential. Fisheries and
      the ecosystems they depend on can only be managed by regulating the activities of
      the fishing industry, and this requires understanding the dynamics of the stocks
      they exploit. 

PMID- 24880796
TI  - The study of deep-sea cephalopods.
AB  - "Deep-sea" cephalopods are here defined as cephalopods that spend a significant
      part of their life cycles outside the euphotic zone. In this chapter, the state
      of knowledge in several aspects of deep-sea cephalopod research are summarized,
      including information sources for these animals, diversity and general
      biogeography and life cycles, including reproduction. Recommendations are made
      for addressing some of the remaining knowledge deficiencies using a variety of
      traditional and more recently developed methods. The types of oceanic gear that
      are suitable for collecting cephalopod specimens and images are reviewed. Many
      groups of deep-sea cephalopods require taxonomic reviews, ideally based on both
      morphological and molecular characters. Museum collections play a vital role in
      these revisions, and novel (molecular) techniques may facilitate new use of old
      museum specimens. Fundamental life-cycle parameters remain unknown for many
      species; techniques developed for neritic species that could potentially be
      applied to deep-sea cephalopods are discussed. Reproductive tactics and
      strategies in deep-sea cephalopods are very diverse and call for comparative
      evolutionary and experimental studies, but even in the twenty-first century,
      mature individuals are still unknown for many species. New insights into diet and
      trophic position have begun to reveal a more diverse range of feeding strategies
      than the typically voracious predatory lifestyle known for many cephalopods.
      Regular standardized deep-sea cephalopod surveys are necessary to provide insight
      into temporal changes in oceanic cephalopod populations and to forecast, verify
      and monitor the impacts of global marine changes and human impacts on these
      populations. 

PMID- 24880797
TI  - Transitions during cephalopod life history: the role of habitat, environment,
      functional morphology and behaviour.
AB  - Cephalopod life cycles generally share a set of stages that take place in
      different habitats and are adapted to specific, though variable, environmental
      conditions. Throughout the lifespan, individuals undertake a series of brief
      transitions from one stage to the next. Four transitions were identified:
      fertilisation of eggs to their release from the female (1), from eggs to
      paralarvae (2), from paralarvae to subadults (3) and from subadults to adults
      (4). An analysis of each transition identified that the changes can be radical
      (i.e. involving a range of morphological, physiological and behavioural phenomena
      and shifts in habitats) and critical (i.e. depending on environmental conditions
      essential for cohort survival). This analysis underlines that transitions from
      eggs to paralarvae (2) and from paralarvae to subadults (3) present major risk of
      mortality, while changes in the other transitions can have evolutionary
      significance. This synthesis suggests that more accurate evaluation of the
      sensitivity of cephalopod populations to environmental variation could be
      achieved by taking into account the ontogeny of the organisms. The comparison of
      most described species advocates for studies linking development and ecology in
      this particular group. 

PMID- 24880798
TI  - Preface.

PMID- 24880799
TI  - Internal abdominal hernia: Intestinal obstruction due to trans-mesenteric hernia
      containing transverse colon.
AB  - INTRODUCTION: Internal abdominal hernias are infrequent but an increasing cause
      of bowel obstruction still often underdiagnosed. Among adults its usual causes
      are congenital anomalies of intestinal rotation, postsurgical iatrogenic, trauma
      or infection diseases. PRESENTATION OF CASE: We report the case of a 63-year-old
      woman with history of chronic constipation. The patient was hospitalized for two
      days with acute abdominal pain, abdominal distension and inability to eliminate
      flatus. The X-ray and abdominal computerized tomography scan (CT scan) showed
      signs of intestinal obstruction. Exploratory laparotomy performed revealed a
      trans-mesenteric hernia containing part of the transverse colon. The intestine
      was viable and resection was not necessary. Only the hernia was repaired.
      DISCUSSION: Internal trans-mesenteric hernia constitutes a rare type of internal
      abdominal hernia, corresponding from 0.2 to 0.9% of bowel obstructions. This type
      carries a high risk of strangulation and even small hernias can be fatal. This
      complication is specially related to trans-mesenteric hernias as it tends to
      volvulize. Unfortunately, the clinical diagnosis is rather difficult. CONCLUSION:
      Trans-mesenteric internal abdominal hernia may be asymptomatic for many years
      because of its nonspecific symptoms. The role of imaging test is relevant but
      still does not avoid the necessity of exploratory surgery when clinical features
      are uncertain.

PMID- 24880800
TI  - The effect of the REG2 Anticoagulation System on thrombin generation kinetics: a
      pharmacodynamic and pharmacokinetic first-in-human study.
AB  - The REG2 Anticoagulation System consists of pegnivacogin, a subcutaneously
      administered aptamer factor IXa inhibitor, and its intravenous active control
      agent, anivamersen. Its effect on thrombin generation is unknown. A prospectively
      designed thrombin generation study was conducted within the phase 1 ascending
      dose study of REG2 to assess the effect of REG2 on thrombin generation kinetics.
      A total of 32 healthy volunteers were recruited into four cohorts of ascending
      dose pegnivacogin for the phase 1 study. In this pre-specified substudy, blood
      samples were drawn in the presence or absence of corn trypsin inhibitor at
      specified times within each dosing cohort. Thrombin generation was initiated with
      tissue factor and thrombin generation kinetics were measured using the Calibrated
      Automated Thrombogram (CAT). REG2 attenuated thrombin generation in a dose
      dependent manner. All parameters of the CAT assay, except for lag time, showed a
      dose and concentration-dependent response to pegnivacogin [time to peak thrombin
      generation (PTm), endogenous thrombin potential, peak thrombin generation, and
      velocity index (VIx)]. Reversal of the effect of pegnivacogin with anivamersen
      demonstrated restoration of thrombin generation without rebound effect. This
      first-in-human study of the effect of the REG2 Anticoagulation System on thrombin
      generation demonstrates concentration-dependent suppression of thrombin
      generation that is reversible without rebound effect, as measured by the CAT
      assay. 

PMID- 24880801
TI  - Linezolid update: stable in vitro activity following more than a decade of
      clinical use and summary of associated resistance mechanisms.
AB  - Linezolid, approved for clinical use since 2000, has become an important addition
      to the anti-Gram-positive infection armamentarium. This oxazolidinone drug has in
      vitro and in vivo activity against essentially all Gram-positive organisms,
      including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin
      resistant enterococci (VRE). The in vitro activity of linezolid was well
      documented prior to its clinical application, and several ongoing surveillance
      studies demonstrated consistent and potent results during the subsequent years of
      clinical use. Emergence of resistance has been limited and associated with
      invasive procedures, deep organ involvement, presence of foreign material and
      mainly prolonged therapy. Non-susceptible organisms usually demonstrate
      alterations in the 23S rRNA target, which remain the main resistance mechanism
      observed in enterococci; although a few reports have described the detection of
      cfr-mediated resistance in Enterococcus faecalis. S. aureus isolates non
      susceptible to linezolid remain rare in large surveillance studies. Most isolates
      harbour 23S rRNA mutations; however, cfr-carrying MRSA isolates have been
      observed in the United States and elsewhere. It is still uncertain whether the
      occurrences of such isolates are becoming more prevalent. Coagulase-negative
      isolates (CoNS) resistant to linezolid were uncommon following clinical approval.
      Surveillance data have indicated that CoNS isolates, mainly Staphylococcus
      epidermidis, currently account for the majority of Gram-positive organisms
      displaying elevated MIC results to linezolid. In addition, these isolates
      frequently demonstrate complex and numerous resistance mechanisms, such as
      alterations in the ribosomal proteins L3 and/or L4 and/or presence of cfr and/or
      modifications in 23S rRNA. The knowledge acquired during the past decades on this
      initially used oxazolidinone has been utilized for developing new candidate
      agents, such as tedizolid and radezolid, and as linezolid patents soon begin to
      expire, generic brands will certainly become available. These events will likely
      establish a new chapter for this successful class of antimicrobial agents. 

PMID- 24880802
TI  - Intracranial hypotension and hypertension in children and adolescents.
AB  - The specific aim of this review is to report the features of intracranial
      pressure changes [spontaneous intracranial hypotension (SIH) and idiopathic
      intracranial hypertension (IIH)] in children and adolescents, with emphasis on
      the presentation, diagnosis, and treatment modalities. Headache associated with
      intracranial pressure changes are relatively rare and less known in children and
      adolescents. SIH is a specific syndrome involving reduced intracranial pressure
      with orthostatic headache, frequently encountered connective tissue disorders,
      and a good prognosis with medical management, initial epidural blood patching,
      and sometimes further interventions may be required. IIH is an uncommon condition
      in children and different from the disease in adults, not only with respect to
      clinical features (likely to present with strabismus and stiff neck rather than
      headache or pulsatile tinnitus) but also different in outcome. Consequently,
      specific ICP changes of pediatric ages required specific attention both of exact
      diagnosis and entire management.

PMID- 24880803
TI  - Role of sphenopalatine ganglion stimulation in cluster headache.
AB  - Cluster headache attacks are characterized by extreme unilateral pain mostly in
      the first trigeminal branch and an ipsilateral activation of the cranial
      parasympathetic system, pointing to a relevant role of the cranial
      parasympathetic system in the pathophysiology, and therapy of cluster headache.
      Based on animal experiments and several interventions of the sphenopalatine
      ganglion (such as an aesthetic or alcoholic blocks and radiofrequency ablation)
      in cluster headache patients, stimulation of the sphenopalatine ganglion (SPGS)
      as the major efferent peripheral parasympathetic structure was established with
      an encouraging abortive effect on acute attacks and a frequency reduction over
      time. In this review, the clinical data and potentially underlying
      pathophysiological concepts of SPGS are discussed in detail, which in brief point
      to a relevant role of the parasympathetic system both in the induction and
      termination of attacks.

PMID- 24880804
TI  - Characterization, N-terminal sequencing and classification of Tolworthcin 524: A
      bacteriocin produced by Bacillus thuringiensis subsp. tolworthi.
AB  - Bacteriocins synthesized by entomopathogenic Bacillus thuringiensis are gaining
      attention owing to their inhibitory effects against a wide variety of pathogenic
      bacteria. In the present study, we purified and characterized Tolworthcin 524, a
      bacteriocin synthesized by B. thuringiensis subsp. tolworthi, and compared it
      with other bacteriocins synthesized by B. thuringiensis. Tolworthcin 524 was
      separated and purified from the secretome of B. thuringiensis by fast protein
      liquid chromatography with a gel filtration column to obtain yields of 17% and a
      specific activity of ~3600U/mgprotein. The purified product showed two peptides
      of ~9 and 6kDa with antimicrobial activity in a gel-screening assay. The purified
      product was analyzed by two-dimensional electrophoresis and the resolved peptides
      of ~9 and 6kDa with isoelectric points of ~8 were sequenced. Partial sequences
      (METPVVQPR and DWTCWSCLVCAACS) were obtained suggesting that the ~9 and 6kDa
      correspond to the prebacteriocin and mature Tolworthcin 524, respectively.
      Sequences showed high identity with Thurincin H and Thuricin 17 and had a
      conserved motif with other bacteriocins of B. thuringiensis. Based on sequence
      data, Tolworthcin 524 was classified in subclass II.2 (Thuricin-like peptides) of
      the Bacillus bacteriocin classification scheme. The larger peptide did not harbor
      a sequence suggestive of a signal peptide neither did it contain the double
      glycine (GG) motif characteristic of the secretion leader recognized by the ABC
      transport system. Implications of these properties in Tolworthcin 524 secretion
      are discussed. 

PMID- 24880805
TI  - Life cycle and spore resistance of spore-forming Bacillus atrophaeus.
AB  - Bacillus endospores have a wide variety of important medical and industrial
      applications. This is an overview of the fundamental aspects of the life cycle,
      spore structure and factors that influence the spore resistance of spore-forming
      Bacillus. Bacillus atrophaeus was used as reference microorganism for this review
      because their spores are widely used to study spore resistance and morphology.
      Understanding the mechanisms involved in the cell cycle and spore survival is
      important for developing strategies for spore killing; producing highly resistant
      spores for biodefense, food and pharmaceutical applications; and developing new
      bioactive molecules and methods for spore surface display. 

PMID- 24880806
TI  - Recovery of phosphorus and nitrogen from alkaline hydrolysis supernatant of
      excess sludge by magnesium ammonium phosphate.
AB  - Magnesium ammonium phosphate (MAP) method was used to recover orthophosphate
      (PO4(3-)-P) and ammonium nitrogen (NH4(+)-N) from the alkaline hydrolysis
      supernatant of excess sludge. To reduce alkali consumption and decrease the pH of
      the supernatant, two-stage alkaline hydrolysis process (TSAHP) was designed. The
      results showed that the release efficiencies of PO4(3-)-P and NH4(+)-N were
      41.96% and 7.78%, respectively, and the pH of the supernatant was below 10.5
      under the running conditions with initial pH of 13, volume ratio (sludge
      dosage/water dosage) of 1.75 in second-stage alkaline hydrolysis reactor, 20 g/L
      of sludge concentration in first-stage alkaline hydrolysis reactor. The order of
      parameters influencing MAP reaction was analyzed and the optimized conditions of
      MAP reaction were predicted through the response surface methodology. The
      recovery rates of PO4(3-)-P and NH4(+)-N were 46.88% and 16.54%, respectively
      under the optimized conditions of Mg/P of 1.8, pH 9.7 and reaction time of 15
      min.

PMID- 24880808
TI  - Biomass and lipid production of Chlorella protothecoides under heterotrophic
      cultivation on a mixed waste substrate of brewer fermentation and crude glycerol.
AB  - Biomass and lipid accumulation of heterotrophic microalgae Chlorella
      protothecoides by supplying mixed waste substrate of brewer fermentation and
      crude glycerol were investigated. The biomass concentrations of the old and the
      new C. protothecoides strains on day 6 reached 14.07 and 12.73 g/L, respectively,
      which were comparable to those in basal medium with supplement of glucose and
      yeast extract (BM-GY) (14.47 g/L for old strains and 11.43 g/L for new strains)
      (P>0.05). Approximately 81.5% of total organic carbon and 65.1% of total nitrogen
      in the mixed waste were effectively removed. The accumulated lipid productivities
      of the old and the new C. protothecoides strains in BM-GY were 2.07 and 1.61
      g/L/day, respectively, whereas in the mixed waste, lipid productivities could
      reach 2.12 and 1.81 g/L/day, respectively. Our result highlights a new approach
      of mixing carbon-rich and nitrogen-rich wastes as economical and practical
      alternative substrates for biofuel production.

PMID- 24880807
TI  - An integrated membrane system for the biocatalytic production of 3'-sialyllactose
      from dairy by-products.
AB  - An integrated membrane system was investigated for the production of 3'
      sialyllactose by an engineered sialidase using casein glycomacropeptide (CGMP)
      and lactose as substrates. CGMP was purified by ultrafiltration (UF) to remove
      any small molecules present and then an enzymatic membrane reactor (EMR) was used
      to separate the product and reuse the enzyme. A PLCC regenerated cellulose
      membrane was found to be the most suitable for both the UF purification and EMR.
      Subsequently, nanofiltration (NF) was conducted to increase the purity of the 3'
      sialyllactose by removing the excess lactose present. The NTR7450 membrane
      outperformed others in NF due to its high retention of 3'-sialyllactose (98%) and
      relatively low rejection of lactose (40%). The lactose in the permeate could be
      concentrated by the NF45 membrane and recycled into the EMR. The described
      integrated membrane system enables a more economic and efficient enzymatic
      production of 3'-sialyllactose. 

PMID- 24880809
TI  - Hydrogen production from algal biomass via steam gasification.
AB  - Algal biomasses were tested as feedstock for steam gasification in a dual-bed
      microreactor in a two-stage process. Gasification experiments were carried out in
      absence and presence of catalyst. The catalysts used were 10% Fe2O3-90% CeO2 and
      red mud (activated and natural forms). Effects of catalysts on tar formation and
      gasification efficiencies were comparatively investigated. It was observed that
      the characteristic of algae gasification was dependent on its components and the
      catalysts used. The main role of the catalyst was reforming of the tar derived
      from algae pyrolysis, besides enhancing water gas shift reaction. The tar
      reduction levels were in the range of 80-100% for seaweeds and of 53-70% for
      microalgae. Fe2O3-CeO2 was found to be the most effective catalyst. The maximum
      hydrogen yields obtained were 1036 cc/g algae for Fucus serratus, 937 cc/g algae
      for Laminaria digitata and 413 cc/g algae for Nannochloropsis oculata.

PMID- 24880810
TI  - Minimizing asynchronism to improve the performances of anaerobic co-digestion of
      food waste and corn stover.
AB  - To investigate the existence of the asynchronism during the anaerobic co
      digestion of different substrates, two typical substrates of food waste and corn
      stover were anaerobically digested with altering organic loadings (OL). The
      results indicated that the biodegradability of food waste and corn stover was
      calculated to be 81.5% and 55.1%, respectively, which was main reason causing the
      asynchronism in the co-digestion. The asynchronism was minimized by NaOH
      pretreatment for corn stover, which could improve the biodegradability by 36.6%.
      The co-digestion with pretreatment could increase the biomethane yield by 12.2%,
      3.2% and 0.6% comparing with the co-digestion without pretreatment at C/N ratios
      of 20, 25 and 30 at OL of 35 g-VS/L, respectively. The results indicated that the
      digestibility synchronism of food waste and corn stover was improved through
      enhancing the accessibility and digestibility of corn stover. The biomethane
      production could be increased by minimizing the asynchronism of two substrates in
      co-digestion.

PMID- 24880811
TI  - Catalytic upgrading of duckweed biocrude in subcritical water.
AB  - Herein, a duckweed biocrude produced from the hydrothermal liquefaction of Lemna
      minor was treated in subcritical water with added H2. Effects of several
      different commercially available materials such as Ru/C, Pd/C, Pt/C, Pt/gamma
      Al2O3, Pt/C-sulfide, Rh/gamma-Al2O3, activated carbon, MoS2, Mo2C, Co-Mo/gamma
      Al2O3, and zeolite on the yields of product fractions and the deoxygenation,
      denitrogenation, and desulfurization of biocrude at 350 degrees C were examined,
      respectively. All the materials showed catalytic activity for deoxygenation and
      desulfurization of the biocrude and only Ru/C showed activity for
      denitrogenation. Of those catalysts examined, Pt/C showed the best performance
      for deoxygenation. Among all the upgraded oils, the oil produced with Ru/C shows
      the lowest sulfur, the highest hydrocarbon content (25.6%), the highest energy
      recovery (85.5%), and the highest higher heating value (42.6 MJ/kg). The gaseous
      products were mainly unreacted H2, CH4, CO2, and C2H6.

PMID- 24880812
TI  - Improving control and estimation for distributed parameter systems utilizing
      mobile actuator-sensor network.
AB  - This paper proposes a scheme for non-collocated moving actuating and sensing
      devices which is unitized for improving performance in distributed parameter
      systems. By Lyapunov stability theorem, each moving actuator/sensor agent
      velocity is obtained. To enhance state estimation of a spatially distributes
      process, two kinds of filters with consensus terms which penalize the
      disagreement of the estimates are considered. Both filters can result in the well
      posedness of the collective dynamics of state errors and can converge to the
      plant state. Numerical simulations demonstrate that the effectiveness of such a
      moving actuator-sensor network in enhancing system performance and the consensus
      filters converge faster to the plant state when consensus terms are included. 

PMID- 24880813
TI  - Subchronic olanzapine treatment decreases the expression of pancreatic glucose
      transporter 2 in rat pancreatic beta cells.
AB  - BACKGROUND: Olanzapine is a second generation antipsychotic. A common side effect
      in humans is weight gain, but the mechanisms are mostly unknown. AIM: To study
      the effects of subchronic olanzapine treatment on body weight, fasting plasma
      glucose (FPG), fasting insulin (FINS), C-peptide, insulin sensitivity index
      (ISI), and expression of glucose transporter 2 (GLUT2) in rat pancreatic beta
      cells. MATERIALS AND METHODS: Female Sprague-Dawley rats were randomly divided
      into two groups: the olanzapine-treated group and the control group (each n = 8).
      Rats in the olanzapine-treated group intragastrically received olanzapine 5
      mg/kg/day for 28 days; the rats in the control group received the same volume of
      vehicle. FPG and body weight were measured on the 1st, 7th, 14th and 28th day.
      FINS and C-peptide were measured using immunoradiometric assays at baseline and
      on the 28th day. GLUT2 mRNA and protein expressions in pancreatic beta cells were
      analyzed by RT-PCR and western blot. RESULTS: Olanzapine-treated rats had higher
      body weight (227.4 +/- 8.9 vs. 211.0 +/- 9.9 g), FPG (5.86 +/- 0.42 vs. 4.24 +/-
      0.29 mmol/L), FINS (17.34 +/- 3.64 vs. 10.20 +/- 1.50 uIU/mL), and C-peptide
      (0.154 +/- 0.027 vs. 0.096 +/- 0.009 ng/mL) than those in controls (all P < 0.05)
      at the 28th day. Pancreatic beta cells of the olanzapine-treated group showed
      lower ISI (-4.60 +/- 0.23 vs. -3.76 +/- 0.20) and GLUT2 levels (mRNA: 1.12 +/-
      0.02 vs. 2.00 +/- 0.03; protein: 0.884 +/- 0.134 vs. 1.118 +/- 0.221) than those
      in controls (all P < 0.05). CONCLUSIONS: Subchronic olanzapine treatment
      inhibited expression of GLUT2 in rat pancreatic beta cells. Therefore, it may
      disturb glucose metabolism via the insulin resistance of beta cells, but
      confirmation in humans is needed.

PMID- 24880815
TI  - Peri-operative complications in pediatric and adolescent shoulder arthroscopy.
AB  - BACKGROUND: Shoulder arthroscopy is not common in the pediatric and adolescent
      population, but the frequency may be on the rise. The purpose of the study was to
      determine the incidence of acute complications of arthroscopic shoulder surgery
      in children and adolescents. METHODS: A retrospective, cross-sectional review was
      performed identifying patients aged 18 years or less who underwent an
      arthroscopic shoulder procedure from 1997 to 2009 at Institution 1 and 2007 to
      2010 at Institution 2. Exclusion criteria included open procedures and missing
      records. Demographic and surgical data were collected, including intra-operative
      and post-operative complications during the first 6 months. The complications
      were divided into minor (no secondary treatment) and major (secondary treatment
      rendered). RESULTS: Two hundred children, mean age 15.9 years, met criteria and
      73 % were boys. All procedures were performed under general anesthesia, but 51 %
      included inter-scalene regional anesthesia. There were 16 (8.0 %) total
      complications recorded. Major complications occurred in five (2.5 %) patients,
      including two tendinitis/bursitis requiring injections, one broken pain pump
      catheter requiring an accessory incision to retrieve, one pain control
      readmission, and one laceration of the cephalic vein requiring ligation. Minor
      complications occurred in 11 (5.5 %) patients, including allergic reactions,
      transient dysesthesias, headaches, bronchitis, syncope, transient hypotension,
      and uvula swelling. CONCLUSION: Although we found no seriously deleterious
      outcomes, it is important to recognize that an additional service was rendered
      for 2.5 % of children undergoing shoulder arthroscopy. The events that did occur
      may be preventable and this study should serve as a baseline to improve quality
      and safety of shoulder arthroscopy in the pediatric population.

PMID- 24880814
TI  - Pulmonary radiologic findings in common variable immunodeficiency: clinical and
      immunological correlations.
AB  - BACKGROUND: It remains unclear whether interstitial lung disease (ILD) in common
      variable immunodeficiency (CVID) is a consequence of chronic infection or a
      manifestation of dysregulated lymphoid proliferation found in those with this
      condition. OBJECTIVE: To increase understanding of CVID-associated lung disease
      by comparing clinical and immunologic associations in those with bronchiectasis,
      ILD, or no lung disease observed on chest computerized tomography (CT). METHODS:
      Retrospective review of electronic medical records of 61 patients with CVID was
      used to identify clinical and laboratory correlates of bronchiectasis, ground
      glass opacity, and pulmonary nodules on CT scan. RESULTS: Significant clinical
      and immunologic associations were identified for common CT scan findings in CVID.
      Bronchiectasis was strongly correlated with a CD4+ T-cell count lower than 700
      cells/MUL and was associated with a history of pneumonia and older age. Pulmonary
      nodular disease was correlated with increased CD4+:CD8+ T-cell ratios, a history
      of autoimmune hemolytic anemia or immune thrombocytopenic purpura, elevated IgM,
      and younger age. Ground glass opacity had similar clinical and laboratory
      characteristics as those for nodular lung disease but was associated with
      elevated monocyte counts and the presence of liver disease. CONCLUSION: CT
      findings of bronchiectasis or ILD, including ground glass opacity and extensive
      pulmonary nodules, were correlated with selected clinical and laboratory
      characteristics. These results suggest divergent processes of CVID lung disease,
      with bronchiectasis more strongly associated with infection and T-cell
      lymphopenia and ILD more strongly linked with autoimmunity and
      lymphoproliferation.

PMID- 24880816
TI  - The prevalence of bifid iliopsoas tendon on MRI in children.
AB  - OBJECTIVE: The variation in the anatomy of the iliopsoas tendon is important
      information for orthopaedic surgeons operating around the hip. The aim of this
      study was to identify the prevalence of bifid iliopsoas tendons in children on
      magnetic resonance imaging (MRI). METHODS: MRI hip and pelvis images of 50
      sequential children aged 7-15 years were retrieved from our radiology database at
      the Evelina London Children's Hospital from 2007 to 2013. Included were 37
      children with imaging of both hips and 13 children with imaging of one hip only.
      Therefore, our study was based on a total of 87 hips. RESULTS: At least 1 bifid
      tendon was noted in 13 children (26 %). Five children from a total of 37 (14 %)
      with both hips adequately imaged had bilateral bifid tendons. Among all 87
      adequately imaged hips, 18 (21 %) were found to have two discrete distal
      iliopsoas tendons. CONCLUSIONS: Bifid iliopsoas tendon is noted anecdotally by
      surgeons but was only reported in scattered case reports and a few anatomical
      studies until very recently. Our finding is that a bifid iliopsoas tendon with
      two distinct tendinous components at the level of the hip joint is quite common.
      This has clinical significance, particularly in children's orthopaedic surgery
      when an adequate iliopsoas release is important.

PMID- 24880817
TI  - [Imported dengue: an emerging arbovirosis in Spain].
AB  - Dengue is caused by one of 4 serotypes of dengue virus. Only imported cases have
      been reported in Spain. The main clinical findings are fever and exanthema,
      although there may be severe forms, particularly in secondary infections. Five
      children with a primary, non severe dengue infection are presented. The diagnosis
      was based on clinical suspicion and epidemiological history, and confirmed by
      immunochromatography and ELISA tests. The outcome was favourable in all cases. It
      is important to consider this diagnosis in international travellers that present
      with fever within the 14 days of returning from an endemic area, in order to get
      an early diagnosis, adequate treatment and a good prognosis. 

PMID- 24880818
TI  - Membranous nephropathy associated with angiomatoid fibrous histiocytoma in a
      pediatric patient.
AB  - BACKGROUND: Though membranous nephropathy is a much more common cause of
      nephrotic syndrome in the adult population, it accounts for only a small fraction
      of cases in pediatrics. CASE-DIAGNOSIS/TREATMENT: We report a case of a 16-year
      old boy with nephrotic syndrome due to membranous nephropathy in the setting of a
      rare tumor, angiomatoid fibrous histiocytoma. This patient's nephrotic-range
      proteinuria completely resolved following resection of this tumor. Angiomatoid
      fibrous histiocytoma, while known to cause other paraneoplastic syndromes such as
      anemia, has never been reported to cause membranous nephropathy. CONCLUSIONS:
      This case highlights a novel and treatable secondary cause of membranous
      nephropathy. Because secondary causes are more common in children than in adults,
      a high index of suspicion for other underlying pathology including malignancy
      should be considered. It also suggests that urinalysis may be a helpful screening
      tool in cases of angiomatoid fibrous histiocytoma.

PMID- 24880819
TI  - Urinary angiotensinogen and urinary sodium are associated with blood pressure in
      normoalbuminuric children with diabetes.
AB  - BACKGROUND: The aim of this study was to evaluate the association between blood
      pressure (BP) and urinary angiotensinogen excretion (uAGT) and renal sodium
      excretion (uNa) in children with type 1 diabetes mellitus (DM1). METHODS: The
      study group consisted of 52 children with DM1 (28 males and 24 females) with
      albumin/creatinine ratio (ACR) below 30 mg/g and glomerular filtration rate
      (eGFR) above 90 ml/min/1.73 m(2). BP was assessed by 24-h ambulatory blood
      pressure monitoring (ABPM). RESULTS: The patients showed significantly increased
      uAGT values with respect to controls (median 0.00 and range 1.76 vs. 0.00 and
      0.00 ng/mg, respectively). The significant increase of uAGT was observed even in
      prehypertensive patients. uAGT concentrations showed positive correlation with
      systolic and diastolic 24-h BP and with mean arterial pressure (MAP) (r = 0.594).
      uNa values were negatively correlated with BP parameters, uAGT, ACR and eGFR.
      CONCLUSIONS: An increase in uAGT precedes hypertension (HTN) in normoalbuminuric
      children with DM1 and may be considered as a new marker of HTN. Decreased sodium
      excretion seems to be involved in the development of HTN and early renal injury.
      Both uAGT and uNa are associated with BP in normoalbuminuric diabetic children.

PMID- 24880820
TI  - Actinomyces osteomyelitis in bisphosphonate-related osteonecrosis of the jaw
      (BRONJ): the missing link?
AB  - Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a rare complication of
      bisphosphonate treatment characterized by the development of exposed, necrotic
      bone in the jaw with inflammatory signs. The pathogenesis of BRONJ is not yet
      fully understood. This review analyzes the evidence supporting the hypothesis
      that BRONJ may be considered as a bisphosphonate-induced Actinomyces infection of
      the jaw according to the modified Koch's postulates. The main arguments relies on
      the following factors: (1) the high prevalence of isolation of Actinomyces from
      bone BRONJ lesions (73.2 % in retrospective series); (2) the similar pathological
      appearance of BRONJ and Actinomyces osteomyelitis in most studies, although BRONJ
      lesions without inflammation have been reported; (3) the high incidence of events
      that disrupt the normal mucosal barrier as a necessary trigger to develop BRONJ
      in bisphosphonate-exposed patients; (4) the predilection of bisphosphonate
      induced osteonecrosis for the bones of the jaws; and (5) the favorable response
      of BRONJ on treatment that is active on Actinomyces. If BRONJ confirms to be a
      bisphosphonate-induced Actinomyces osteomyelitis of the jaw, this has major
      consequences for the prevention and treatment of this condition.

PMID- 24880821
TI  - Providing prescheduled appointments as a strategy for improving follow-up
      compliance after community-based glaucoma screening: results from an urban
      underserved population.
AB  - To determine if receiving a prescheduled appointment is associated with an
      increased likelihood of complying with follow-up eye care among individuals
      identified as at risk for glaucoma during community-based glaucoma screening in
      an urban underserved population. This study sampled 362 individuals aged >=30
      years without known glaucoma from low-income, predominantly black/Hispanic
      neighborhoods in New Haven, Connecticut presenting to one of twelve community
      based glaucoma screening events from May 2010 to October 2012. A quasi
      experimental design systematically assigned 63 individuals identified as at risk
      for glaucoma into either intervention or control group with a 1:2 ratio.
      Individuals in the control group (n = 41) received counseling on glaucoma and a
      recommendation for obtaining a follow-up appointment at the eye department of a
      local community health center, which offers affordable health services with
      income-adjusted fee discounts to uninsured, low-income patients. Those in the
      intervention group (n = 22) received the same counseling and a prescheduled
      appointment at the community health center. The overall rate of follow-up
      compliance within 3 months of screening was 30 % (41 % in the intervention group;
      24 % in the control group). Multivariate logistic regression analysis adjusting
      for sex, age, ethnicity, health insurance status, car access, living situation,
      and smoking status found that follow-up compliance was significantly associated
      with intervention (adjusted odds ratio 4.8; 95 % confidence interval 1.1-20.9).
      Providing prescheduled appointments can improve follow-up compliance after
      community-based glaucoma screening. This finding may be potentially applicable to
      community-based health screening for other preventable diseases.

PMID- 24880822
TI  - Nutrition students gain skills from motivational interviewing curriculum.

PMID- 24880824
TI  - [Wine: Good for all cardiovascular diseases?].
AB  - Beneficial effects of wine are mainly due to polyphenol components with a major
      role for resveratrol. Moderate wine consumption decreases cardiovascular
      mortality. Very favorable effects in coronary artery disease and cholesterol.
      Deleterious effects in systemic hypertension and dilated cardiomyopathy.
      RECOMMENDATION: 1 to 2 drinks (10 to 20g of alcohol) per day.

PMID- 24880823
TI  - Characterization of carbapenem-resistant Acinetobacter baumannii in Brazil (2008
      2011): countrywide spread of OXA-23-producing clones (CC15 and CC79).
AB  - The study investigated the genetic relationship of carbapenem-resistant
      Acinetobacter baumannii clinical isolated from inpatients during 2008-2011 from
      11 Brazilian states. Antimicrobial susceptibility profile was determined by disc
      diffusion method and Etest. Polymerase chain reaction was applied for
      carbapenemase genes, and ISAba1. Isolates were subjected to pulsed field gel
      electrophoresis (PFGE) and multilocus sequence typing (MLST) for molecular
      typing. Most of the isolates showed high resistance rates to antibiotics tested.
      The blaOXA-51-like gene was found in all isolates, and 146 (94.2%) isolates were
      positive for blaOXA-23-like. In the most OXA-23-producing isolates, the blaOXA-23
      like gene was accompanied by ISAba1. A total of 146 OXA-23-producing isolates
      were clustered into 28 genotypes by PFGE. Molecular analysis by MLST identified
      13 sequence types (STs). The most prevalent PFGE profiles were designated as ST15
      (CC15), ST1 (CC1), and ST79 (CC79). This study showed the widespread of clonal
      complexes of A. baumannii harboring the blaOXA-23-like gene in different
      Brazilian states. 

PMID- 24880825
TI  - Single-lung transplantation with ABO-compatible donors results in excellent
      outcomes.
AB  - BACKGROUND: The goal of this study was to determine if carefully selected ABO
      compatible donors in single-lung transplantation results in acceptable outcomes.
      METHODS: The United Network for Organ Sharing database was reviewed for adult
      single-lung transplant recipients from May 2005 to December 2011. Recipients of
      lungs from ABO-compatible donors were compared with those of ABO-identical
      donors. Mortality was examined with risk-adjusted multivariable Cox proportional
      hazards regression using significant univariate predictors. RESULTS: Of 3,572
      single-lung transplants, 342 (9.6%) were from ABO-compatible donors. The two
      groups were evenly matched in recipient age (60.8 vs 60.2 years, p = 0.28), male
      gender (61.8% vs 58.2%, p = 0.10), lung allocation score (43.4 vs 42.6, p =
      0.32), forced expiratory volume in 1 second (FEV1; 41.2% vs 40.8%, p = 0.32), and
      ischemic time (4.2 vs 4.0 hours, p = 0.09), and donor age (34.4 vs 32.9, p =
      0.07) and male gender (61.5 vs 65.5, p = 0.14). ABO-compatible donors were less
      likely to be race mismatched (58.3% vs 50.9%, p = 0.01). Median survival was not
      different (1,284.0 vs 1,540 days, p = 0.39). On multivariate analysis, lungs from
      ABO-compatible donors were not associated with mortality (hazard ratio, 1.02; 95%
      confidence interval, 0.85-1.22; p = 0.86). Prolonged ischemic time, increasing
      recipient creatinine, increasing recipient age, race mismatch, class I plasma
      reactive antigen panel > 10%, and the use of mechanical ventilation or
      extracorporeal membrane oxygenation were associated with mortality. Peak post
      transplant FEV1 (64.5% vs 64.0%, p = 0.69) and decrement in FEV1 over time were
      similar (p = 0.82). CONCLUSIONS: This large multi-institutional analysis of ABO
      compatible donors in single-lung transplantation demonstrates that careful
      selection of ABO-compatible donors results in excellent outcomes.

PMID- 24880826
TI  - Are we ready for the age of non-invasive haemodynamic monitoring?

PMID- 24880827
TI  - Issue and challenges of fluid removal in the critically ill.

PMID- 24880828
TI  - Endothelial progenitor cell mobilization by preoperative exercise: a bone marrow
      response associated with postoperative outcome.
AB  - BACKGROUND: Preoperative anaemia is associated with increased morbidity in
      patients undergoing major surgery. Whether erythrocytes are the only bone-marrow
      derived cell lineage that associates with increased surgical complications is
      unknown. This prospective observational trial studied the mobilization of
      endothelial progenitor cells (EPCs) in response to exercise in association with
      postoperative complications. METHODS: After IRB approval, 60 subjects undergoing
      major thoracic surgery were exercised to exhaustion (peak V(O2)). Peripheral
      blood collected before and after peak exercise was quantified for EPC lineages by
      fluorescence-activated cell sorter analysis. Complication analysis was based on
      the Clavien-Dindo classification. RESULTS: Exhaustive exercise increased EPC
      [CD45-133+34+ cells=150 (0.00-5230) to 220 (0.00-1270) cells MUl(-1); median
      change (range)=20 (-4,180-860) cells MUl(-1); P=0.03] but not mature endothelial
      cell (EC) subpopulations. Pre-exercise levels [odds ratio (OR)=0.86, 95%
      confidence interval (CI): 0.37-2.00, P=0.72), change after exercise as a
      continuous variable (OR=0.95, 95% CI: 0.41-2.22, P=0.91) and a positive response
      after exercise (change >0 cells MUl(-1); OR=0.41, 95% CI: 0.13-1.28, P=0.12) were
      not statistically significantly associated with the incidence of postoperative
      complications. Post-hoc receiver operating characteristic curve analyses revealed
      that subjects with a CD45-133+34+ increase >=60 cells MUl(-1) in response to
      exercise suffered fewer postoperative complications [86% sensitivity, 48%
      specificity and AUC=0.67 (95% CI: 0.52-0.81)]. CONCLUSIONS: Preoperative exercise
      induces EPC into the peripheral circulation. Subjects with a poor EPC response
      had a pre-existing propensity for postoperative complications. This warrants
      further research into the role of bone marrow function as a critical component to
      endothelial repair mechanisms. CLINICAL TRIAL REGISTRATION: IRB 2003-0434
      (University of Texas M.D. Anderson Cancer Center, Houston, TX, USA).

PMID- 24880829
TI  - Clinical Trials without conceptual foundation may produce flawed results for the
      management of fluid therapy in the critically ill.

PMID- 24880831
TI  - Reducing the global prevalence of overweight and obesity.

PMID- 24880833
TI  - Proposed AJO-DO Resource Center on cone-beam computed tomography imaging.

PMID- 24880832
TI  - Collaborative EDNAP exercise on the IrisPlex system for DNA-based prediction of
      human eye colour.
AB  - The IrisPlex system is a DNA-based test system for the prediction of human eye
      colour from biological samples and consists of a single forensically validated
      multiplex genotyping assay together with a statistical prediction model that is
      based on genotypes and phenotypes from thousands of individuals. IrisPlex
      predicts blue and brown human eye colour with, on average, >94% precision
      accuracy using six of the currently most eye colour informative single nucleotide
      polymorphisms (HERC2 rs12913832, OCA2 rs1800407, SLC24A4 rs12896399, SLC45A2
      (MATP) rs16891982, TYR rs1393350, and IRF4 rs12203592) according to a previous
      study, while the accuracy in predicting non-blue and non-brown eye colours is
      considerably lower. In an effort to vigorously assess the IrisPlex system at the
      international level, testing was performed by 21 laboratories in the context of a
      collaborative exercise divided into three tasks and organised by the European DNA
      Profiling (EDNAP) Group of the International Society of Forensic Genetics (ISFG).
      Task 1 involved the assessment of 10 blood and saliva samples provided on FTA
      cards by the organising laboratory together with eye colour phenotypes; 99.4% of
      the genotypes were correctly reported and 99% of the eye colour phenotypes were
      correctly predicted. Task 2 involved the assessment of 5 DNA samples extracted by
      the host laboratory from simulated casework samples, artificially degraded, and
      provided to the participants in varying DNA concentrations. For this task, 98.7%
      of the genotypes were correctly determined and 96.2% of eye colour phenotypes
      were correctly inferred. For Tasks 1 and 2 together, 99.2% (1875) of the 1890
      genotypes were correctly generated and of the 15 (0.8%) incorrect genotype calls,
      only 2 (0.1%) resulted in incorrect eye colour phenotypes. The voluntary Task 3
      involved participants choosing their own test subjects for IrisPlex genotyping
      and eye colour phenotype inference, while eye photographs were provided to the
      organising laboratory and judged; 96% of the eye colour phenotypes were inferred
      correctly across 100 samples and 19 laboratories. The high success rates in
      genotyping and eye colour phenotyping clearly demonstrate the reproducibility and
      the robustness of the IrisPlex assay as well as the accuracy of the IrisPlex
      model to predict blue and brown eye colour from DNA. Additionally, this study
      demonstrates the ease with which the IrisPlex system is implementable and
      applicable across forensic laboratories around the world with varying pre
      existing experiences. 

PMID- 24880834
TI  - Concern about selection of the subjects.

PMID- 24880835
TI  - Authors' response.

PMID- 24880836
TI  - Thirty-two-year follow-up study of Herbst therapy.

PMID- 24880837
TI  - Author's response.

PMID- 24880838
TI  - Treatment of open bite and closing of relapsed space.

PMID- 24880830
TI  - Global, regional, and national prevalence of overweight and obesity in children
      and adults during 1980-2013: a systematic analysis for the Global Burden of
      Disease Study 2013.
AB  - BACKGROUND: In 2010, overweight and obesity were estimated to cause 3.4 million
      deaths, 3.9% of years of life lost, and 3.8% of disability-adjusted life-years
      (DALYs) worldwide. The rise in obesity has led to widespread calls for regular
      monitoring of changes in overweight and obesity prevalence in all populations.
      Comparable, up-to-date information about levels and trends is essential to
      quantify population health effects and to prompt decision makers to prioritise
      action. We estimate the global, regional, and national prevalence of overweight
      and obesity in children and adults during 1980-2013. METHODS: We systematically
      identified surveys, reports, and published studies (n=1769) that included data
      for height and weight, both through physical measurements and self-reports. We
      used mixed effects linear regression to correct for bias in self-reports. We
      obtained data for prevalence of obesity and overweight by age, sex, country, and
      year (n=19,244) with a spatiotemporal Gaussian process regression model to
      estimate prevalence with 95% uncertainty intervals (UIs). FINDINGS: Worldwide,
      the proportion of adults with a body-mass index (BMI) of 25 kg/m(2) or greater
      increased between 1980 and 2013 from 28.8% (95% UI 28.4-29.3) to 36.9% (36.3
      37.4) in men, and from 29.8% (29.3-30.2) to 38.0% (37.5-38.5) in women.
      Prevalence has increased substantially in children and adolescents in developed
      countries; 23.8% (22.9-24.7) of boys and 22.6% (21.7-23.6) of girls were
      overweight or obese in 2013. The prevalence of overweight and obesity has also
      increased in children and adolescents in developing countries, from 8.1% (7.7
      8.6) to 12.9% (12.3-13.5) in 2013 for boys and from 8.4% (8.1-8.8) to 13.4% (13.0
      13.9) in girls. In adults, estimated prevalence of obesity exceeded 50% in men in
      Tonga and in women in Kuwait, Kiribati, Federated States of Micronesia, Libya,
      Qatar, Tonga, and Samoa. Since 2006, the increase in adult obesity in developed
      countries has slowed down. INTERPRETATION: Because of the established health
      risks and substantial increases in prevalence, obesity has become a major global
      health challenge. Not only is obesity increasing, but no national success stories
      have been reported in the past 33 years. Urgent global action and leadership is
      needed to help countries to more effectively intervene. FUNDING: Bill & Melinda
      Gates Foundation.

PMID- 24880839
TI  - Authors' response.

PMID- 24880840
TI  - Ethics in orthodontics. Joint autonomy.

PMID- 24880842
TI  - Comparison of vacuum-formed and Hawley retainers: a systematic review.
AB  - INTRODUCTION: Hawley retainers (HRs) and vacuum-formed retainers (VFRs) are the 2
      most commonly used retainers in orthodontics. However, the basis for selection of
      an appropriate retainer is still a matter of debate among orthodontists. In this
      systematic review, we evaluated the differences between VFRs and HRs. METHODS:
      Electronic databases (PubMed, EMBASE, Cochrane Library, ISI Web of Science,
      LILACS, and Pro-Quest) were searched with no language restriction. The relevant
      orthodontic journals and reference lists were checked for all eligible studies.
      Two article reviewers independently screened the retrieved studies, extracted the
      data, and evaluated the quality of the primary studies. RESULTS: A total of 89
      articles were retrieved in the initial search. However, only 7 articles met the
      inclusion criteria. Some evidence suggested that no difference exists to
      distinguish between the HRs and VFRs with respect to changes in intercanine and
      intermolar widths after orthodontic retention. In terms of occlusal contacts,
      cost effectiveness, patient satisfaction, and survival time, there was
      insufficient evidence to support the use of VFRs over HRs. CONCLUSIONS:
      Additional high-quality, randomized, controlled trials concerning these retainers
      are necessary to determine which retainer is better for orthodontic procedures.

PMID- 24880843
TI  - Forces and moments generated by removable thermoplastic aligners: incisor torque,
      premolar derotation, and molar distalization.
AB  - INTRODUCTION: The exact force systems as well as their progressions generated by
      removable thermoplastic appliances have not been investigated. Thus, the purposes
      of this experimental study were to quantify the forces and moments delivered by a
      single aligner and a series of aligners (Invisalign; Align Technology, Santa
      Clara, Calif) and to investigate the influence of attachments and power ridges on
      the force transfer. METHODS: We studied 970 aligners of the Invisalign system (60
      series of aligners). The aligners came from 30 consecutive patients, of which 3
      tooth movements (incisor torque, premolar derotation, molar distalization) with
      20 movements each were analyzed. The 3 movement groups were subdivided so that 10
      movements were supported with an attachment and 10 were not. The patients'
      ClinCheck (Align Technology, Santa Clara, Calif) was planned so that the
      movements to be investigated were performed in isolation in the respective
      quadrant. Resin replicas of the patients' intraoral situation before the start of
      the investigated movement were taken and mounted in a biomechanical measurement
      system. An aligner was put on the model, the force systems were measured, and the
      calculated movements were experimentally performed until no further forces or
      moments were generated. Subsequently, the next aligners were installed, and the
      measurements were repeated. RESULTS: The initial mean moments were about 7.3 N.mm
      for maxillary incisor torque and about 1.0 N for distalization. Significant
      differences in the generated moments were measured in the premolar derotation
      group, whether they were supported with an attachment (8.8 N.mm) or not (1.2
      N.mm). All measurements showed an exponential force change. CONCLUSIONS: Apart
      from a few maximal initial force systems, the forces and moments generated by
      aligners of the Invisalign system are within the range of orthodontic forces. The
      force change is exponential while a patient is wearing removable thermoplastic
      appliances.

PMID- 24880844
TI  - Local application of zoledronate enhances miniscrew implant stability in dogs.
AB  - INTRODUCTION: The primary purposes of this study were to evaluate how locally
      delivered zoledronate affects the longitudinal stability of miniscrew implants
      (MSIs) and the healing of bone around MSIs. METHODS: Using a randomized split
      mouth design, 60 unloaded MSIs (5 * 1.6 mm) were placed in skeletally mature male
      foxhound-mixed breed dogs. The MSIs were randomly assigned to bilateral pairs of
      pilot holes (1.1 mm) that had been injected with either bisphosphonate
      zoledronate (n = 30, experimental group) or buffered saline solution (n = 30,
      control group). MSI stability was evaluated weekly for 8 weeks using resonance
      frequency analyses (Osstell Mentor; Integration Diagnostics, Goteborg, Sweden).
      Microcomputed tomography (6-MUm voxel size) was used to determine the bone volume
      fractions of 3 layers of bone (6-24, 24-42, and 42-60 MUm) surrounding the MSIs.
      RESULTS: Resonance frequency analysis showed that the control MSIs were
      significantly (P <0.05) less stable than the experimental MSIs. Although there
      was little or no change in stability over time for the MSIs treated with
      zoledronate, the stability of the control MSIs decreased during the first 4
      weeks, increased through week 6, and then decreased again. The 6- to 24-MUm layer
      closest to the MSIs, on both the experimental and the control sides, showed
      significantly (P <0.05) less bone than did the 24- to 42-MUm and the 42- to 60
      MUm layers. After 8 weeks, there was significantly more cortical bone surrounding
      the control than the experimental MSIs. In contrast, there was significantly more
      trabecular bone surrounding the experimental than the control MSIs. CONCLUSIONS:
      One small locally delivered dose of zoledronate maintained the stability of MSIs
      over time, primarily because of greater amounts of trabecular bone surrounding
      the MSIs. Even though zoledronate enhanced the stability of MSIs in dogs, it
      should not be used clinically until further studies confirm its safe use in
      patients.

PMID- 24880845
TI  - Differences in facial profile and dental esthetic perceptions between young
      adults and orthodontists.
AB  - INTRODUCTION: The principal aim of this study was to investigate differences in
      perception of soft-tissue facial profiles and dental esthetics between young
      Chinese adults and orthodontists. METHODS: Eight hundred ninety-two subjects (444
      male, 448 female), ages 16 to 24 years, chose 1 image from among 5 profile
      silhouettes and from among 10 ranked color photographs of the aesthetic component
      (AC) of the index of orthodontic treatment need that most closely resembled their
      own profile and dental esthetic appearance, respectively. A panel of 20
      orthodontists then independently repeated the same image selection process. Each
      subject also completed the Eysenck personality questionnaire for psychoticism. We
      used the Mann-Whitney U test and the Spearman rank correlation test, with
      statistical significance set at alpha = 0.05. RESULTS: Only 37.0% of subjects had
      straight profiles by objective orthodontic assessment, but 85.0% chose straight
      profiles by subjective self-perception. About 17.5%, mainly females, chose the
      mild convex as the ideal profile. Only 2.5% of the subjects were ranked 1 on the
      AC by orthodontists, but 43.6% chose 1, or ideal, by self-perception. Male
      subjects scored significantly higher than did female subjects for self-perceived
      facial profiles (more protruded chins) and for the AC (more attractive dental
      appearance). Subjects with high psychoticism T scores (>50) scored significantly
      lower for self-perceived facial profiles (more retruded chins) and on the AC
      (less attractive dental appearance). CONCLUSIONS: Young Chinese adults perceived
      their facial profiles and dental appearances to be significantly more straight
      and attractive, respectively, than did the orthodontists. A significant
      proportion of the young adults, mainly women, preferred a mild convex facial
      profile. High psychoticism scores might significantly affect the self-perception
      of orthodontic treatment needs.

PMID- 24880846
TI  - Microsatellite genome-wide association study for mandibular prognathism.
AB  - INTRODUCTION: Attempts have been made to identify susceptibility genes of
      mandibular prognathism by genome-wide linkage studies, but the results of
      susceptibility loci are inconsistent. There has been no genome-wide association
      study of mandibular prognathism. Our objective was to perform a genome-wide
      association study using 23,465 microsatellite markers to detect mandibular
      prognathism susceptibility regions. METHODS: The study was based on the pooled
      DNA method, including 2 steps of screening on the whole genome and subsequent
      individual genotyping, with 240 experimental subjects and 360 control subjects
      from the Japanese population. RESULTS: Two suggestive associations on chromosomes
      1q32.2 (D1S1358i: P = 4.22 * 10(-4)) and 1p22.3 (D1S0411i: P = 6.66 * 10(-4))
      were shown, and PLXNA2 and SSX2IP were suggested to be candidate genes; 1p22.3
      flanked the region indicated by previous linkage analysis. CONCLUSIONS: The
      results of the genome-wide association study showed that 2 loci (1q32.2 and
      1p22.3) are likely to be susceptibility regions of mandibular prognathism: 1p32.2
      is a novel locus, and identification of 1p22.3 supports the results of previous
      linkage analysis.

PMID- 24880847
TI  - Longitudinal evaluation of dental arch asymmetry in Class II subdivision
      malocclusion with 3-dimensional digital models.
AB  - INTRODUCTION: Class II subdivision malocclusions with their asymmetric occlusal
      relationships often pose treatment difficulties. The aim of this study was to
      evaluate the longitudinal changes of dental arch asymmetry in untreated subjects
      with Class II subdivision malocclusion. METHODS: From 706 files from the
      University of Michigan Growth Study, longitudinal records of 17 untreated
      subjects with Class II subdivision malocclusion were included this study. Dental
      arch changes at 3 consecutive longitudinal intervals, defined by the cervical
      vertebral maturation method, were analyzed on digital dental models. The average
      ages of the subjects were 12.4, 15.1, and 19.1 years at the 3 time periods,
      respectively. Maxillary and mandibular reference lines were constructed and used
      for the intra-arch asymmetry measurements. The Friedman test and analysis of
      variance with repeated measures were used to determine dental arch asymmetries at
      the P <0.05 level. RESULTS: All subjects were found to have a type 1 Class II
      subdivision malocclusion characterized by distal positioning of the mandibular
      first molar on the Class II side. No statistically significant intra-arch
      asymmetry changes were found for the maxillary and mandibular dental arches in
      any time period. Between the baseline and the final follow-up, the data indicated
      decreases in maxillary and mandibular intercanine arch widths and arch lengths
      symmetrically. CONCLUSIONS: The results of this study indicate that the dental
      arch asymmetry in patients with Class II subdivision malocclusions did not
      improve or worsen with growth.

PMID- 24880848
TI  - Immediate changes in condylar position after rapid maxillary expansion.
AB  - INTRODUCTION: Although the dentoalveolar and skeletal effects of rapid maxillary
      expansion are well documented, the condylar response to this procedure is not
      well understood. The purpose of this study was to test the following null
      hypothesis: rapid maxillary expansion promotes immediate changes of the position
      of the condyles in patients with Class I malocclusion. METHODS: Thirty-four
      subjects with Class I malocclusion underwent rapid maxillary expansion. Cone-beam
      computed tomography images were collected before activation of the expander and 3
      weeks later, after screw stabilization. Using specific software functions, it was
      possible to determine and reproduce head positioning and landmarks during the
      different times of the study. RESULTS: The axial, coronal, and sagittal planes
      were examined, and no asymmetries in condylar positions were found at either
      time. However, statistically significant anterior and inferior displacements of
      these structures occurred, with respective average values of 0.52 and 0.49 mm.
      Lateral inclinations of both condyles were observed and confirmed by the coronal
      condylar angles. CONCLUSIONS: The null hypothesis was rejected. Statistically
      significant anterior and inferior displacements of the condyles occurred. Lateral
      inclination of the condyles was observed.

PMID- 24880849
TI  - Three-dimensional evaluation of the pharyngeal airway volumes in patients
      affected by unilateral cleft lip and palate.
AB  - INTRODUCTION: Patients affected by cleft lip and palate often have complaints of
      snoring and respiratory difficulties during sleep. The purposes of this study
      were to evaluate nasopharyngeal, oropharyngeal, and total airway volumes of
      patients affected by unilateral cleft lip and palate and to compare them with a
      well-matched control group without unilateral cleft lip and palate using cone
      beam computed tomography. METHODS: The study sample consisted of 60 patients (26
      girls, 34 boys) divided into 2 groups: unilateral cleft lip and palate (20 boys,
      10 girls; 8 right sided, 22 left sided; mean age, 14.6 +/- 3.2 years) and no
      cleft (control group; 14 boys, 16 girls; mean age, 14.8 +/- 2.8 years).
      Nasopharyngeal, oropharyngeal, and total airway volumes of the subjects in both
      groups were calculated 3 dimensionally with cone-beam computed tomography. Group
      differences in relation to cleft side, sex, and cleft presence were statistically
      tested at P <0.05. RESULTS: Patients affected by unilateral cleft lip and palate
      had similar airway volumes regardless of the side of the cleft. In addition, no
      statistically significant differences were found between the sexes in the 2
      groups. Patients affected by unilateral cleft lip and palate had smaller
      nasopharyngeal, oropharyngeal, and total airway volumes when compared with the
      control group. The difference for oropharyngeal airway volume (-4036.7 mm(3)) was
      statistically significant (P <0.05), whereas nasopharyngeal volume (-21.6 mm(3))
      and total airway volume (-4057.3 mm(3)) differences were not significant (P
      >0.05). CONCLUSIONS: Patients affected by unilateral cleft lip and palate had
      decreased volumes of oropharyngeal (P <0.05) and total (P >0.05) airways compared
      with the well-matched control group without unilateral cleft lip and palate.

PMID- 24880850
TI  - Mass spectrometry analysis of gingival crevicular fluid in the presence of
      external root resorption.
AB  - INTRODUCTION: In this study, we used liquid chromatography-mass spectrometry (LC
      MS) to investigate the differences in the composition of gingival crevicular
      fluid between resorbing deciduous molars and nonresorbing permanent teeth. The
      main goal was to identify novel biomarkers associated with root resorption.
      METHODS: Eleven children (4 boys, 7 girls) in the mixed dentition were selected
      to participate in this split-mouth design study, in which a deciduous second
      molar with radiographic evidence of root resorption served as the experimental
      site, and the permanent first molar on the contralateral quadrant was the control
      site. Gingival crevicular fluid was collected using absorbing strips. A total of
      22 samples (11 root resorption, 11 control) were each analyzed with 1-dimensional
      LC-MS. The remaining samples were then pooled across the 11 patients and analyzed
      by 2-dimensional LC-MS. The output files were converted to mascot generic format,
      which can be used to perform protein identification with conventional search
      engines. RESULTS: The 2-dimensional LC-MS protocol was able to identify 2789 and
      2421 proteins in the control and resorption pooled samples, respectively. In this
      population, we detected significantly upregulated and downregulated proteins in
      the teeth with root resorption. Interestingly, many of these proteins are
      characteristically found in exosomes. CONCLUSIONS: We identified novel proteins
      that might prove to be useful biomarkers of root resorption, individually or as
      part of a panel.

PMID- 24880851
TI  - Do long-faced subjects really have a long anterior face? A longitudinal study.
AB  - INTRODUCTION: The aims of this study were to investigate and compare the anterior
      facial heights of children with long, normal, and short faces during growth and
      to discover whether long-faced subjects have long dimensions in both the upper
      and lower anterior facial heights compared with the others. METHODS: Longitudinal
      lateral cephalometric data of 167 children (83 girls, 84 boys) from 6 to 14 years
      of age were used. Total anterior face height, upper anterior face height, lower
      anterior face height, and the closest distance from the Frankfort horizontal
      plane to nasion were measured. The samples were classified as long-faced, normal
      faced, and short-faced according to the ratio of lower to total face heights at
      14 years old. All data were analyzed statistically and compared between the
      groups according to age. RESULTS: The mean lower anterior face height in the long
      faced group was larger than in the normal-faced and short-faced groups for all
      ages in both sexes. In contrast, subjects in the normal-faced group had a longer
      mean upper anterior face height than did subjects in the long-faced and short
      faced groups. In addition, the mean upper anterior face height of the short-faced
      group was larger than the long-faced group for girls at all ages and for boys at
      12 to 14 years. CONCLUSIONS: The long-faced children did not have longer upper
      facial heights compared with normal-faced and short-faced children, and their
      long faces were mainly determined by the length of the lower face.

PMID- 24880852
TI  - Conservative treatment for a growing patient with a severe, developing skeletal
      Class III malocclusion and open bite.
AB  - An 8-year-old Chinese girl sought treatment for a severe skeletal Class III
      malocclusion and open-bite skeletal pattern. Traditionally, patients with a
      skeletal Class III malocclusion are treated after they have stopped growing, and
      then they are treated with a combined orthodontic and orthognathic surgery
      approach. But the risks and expenses of this treatment plan are not acceptable to
      all patients. This young patient was treated with facemask therapy, a maxillary
      expansion device, and a molar occlusal splint for maxillary developmental
      stimulation with control of vertical jaw growth. After the completion of
      orthopedic therapy, 2 * 4 technology was used to adjust molar positions. A bonded
      tongue crib was used in the early permanent dentition to help the patient break
      her bad tongue habits. Straight-wire appliances were used for 16 months to adjust
      the occlusal relationship. This achieved significant improvement in anterior
      tooth relationships and facial profile esthetics. At the 2-year posttreatment
      follow-up, the results were satisfactory. The success of the sagittal
      relationship correction between the maxilla and the mandible for a skeletal Class
      III malocclusion depends on the coordination of transverse and vertical
      relationships combined with the growth potential of each patient. 

PMID- 24880853
TI  - Use of Forsus fatigue-resistant device in a patient with Class I malocclusion and
      mandibular incisor agenesis.
AB  - Orthodontic treatment in patients with congenitally missing teeth can be
      challenging. In this case report, we describe the treatment of a 15-year-old girl
      with mild dental crowding and 2 congenitally missing mandibular incisors. The
      Forsus fatigue-resistant device was used to move the mandible and the mandibular
      teeth forward. A new balanced and stable occlusion was achieved after treatment.
      When the treatment plan includes moving the mandibular teeth forward in a patient
      with mandibular incisor agenesis, the profile and the skeletal and dental
      features should be carefully scrutinized to ensure that balanced and esthetic
      results are achieved. 

PMID- 24880855
TI  - Litigation and legislation. Possibility, probability, and causation: a study of
      proximate causation.

PMID- 24880854
TI  - Spontaneous improvement of gingival recession after correction of tooth
      positioning.
AB  - A 30-year-old woman sought treatment for malpositioned mandibular incisors; the
      roots were positioned outside the alveolar bone, related to severe localized
      gingival recession. She had been previously treated orthodontically and
      subsequently underwent 2 gingival grafts. The new treatment included torquing the
      roots back within the alveolar bone and referral to a periodontist for a gingival
      graft. In this clinical report, the possible spontaneous improvement of gingival
      recession is discussed. A hypothesis described in the literature is called the
      "creeping attachment" phenomenon. The literature includes conflicting reports
      about the cause-and-effect relationship between orthodontics and gingival
      recession. This clinical example reports spontaneous improvement of gingival
      recession after correction of tooth positioning in the alveolar bone. A gingival
      graft can be performed after adequate root positioning in the alveolar bone
      housing, thus increasing the chance of achieving more favorable results. 

PMID- 24880856
TI  - Effect modification.

PMID- 24880857
TI  - Prevalence of anxiety and depression among diabetic African patients in Guinea:
      association with HbA1c levels.
AB  - AIM: The prevalence and risk factors associated with symptoms of anxiety and
      depression were determined in African people with diabetes. METHODS: This cross
      sectional study involved 491 outpatients with type 2 diabetes (T2D) recruited
      from four diabetes clinics (Conakry, Labe, Boke and Kankan) in Guinea. The
      Hospital Anxiety and Depression Scale (HADS) was used to evaluate symptoms of
      anxiety and depression. Logistic regression analysis stratified by gender was
      performed to identify the associated risk factors. RESULTS: Anxiety and
      depression symptoms were present in 58.7% and 34.4%, respectively, of the 491
      patients with T2D (62.7% women, mean+/-SD age: 57.9+/-10.2years). Odds ratios
      (95% CI) of risk factors independently associated with anxiety were urban
      residence [2.98 (1.81-4.89)] in women, and low socioeconomic status [0.19 (0.05
      0.70)] and HbA1c>=9.0% [2.61 (1.0-6.39)] in men. Factors associated with
      depression were urban residence [2.13 (1.27-3.58)], older age [1.03 (1.01-1.06)],
      low socioeconomic status [2.21 (1.34-3.66)] and no previous measurement of HbA1c
      [12.45 (1.54-100.34)] in women, and insulin therapy [2.28 (1.05-4.92)] and
      HbA1c>=9.0% [3.85 (1.02-14.48)] in men. CONCLUSION: Anxiety and depression
      symptoms in people with type T2D are common in Guinea. Urban residence, low
      socioeconomic status and high levels of HbA1c were significantly associated with
      a greater risk of anxiety and depression, highlighting the psychological burden
      related to diabetes in Africa.

PMID- 24880858
TI  - Prevalence of diabetes and depressive symptomatology and their effect on
      mortality risk in elderly Italians: The Italian Longitudinal Study on Aging.
AB  - AIM: This study assessed the prevalence of depressive symptomatology (DS) in
      older individuals with diabetes to determine whether diabetes and DS are
      independent predictors of mortality, and if their coexistence is associated with
      an increased mortality risk. METHODS: Analyses were based on data from the
      Italian Longitudinal Study on Aging (ILSA), a prospective community-based cohort
      study in which 5632 individuals aged 65-84years were enrolled. The role of
      diabetes and DS in all-cause mortality was evaluated using the Cox model,
      adjusted for possible confounders, for four groups: 1) those with neither
      diabetes nor DS (reference group); 2) those with DS but without diabetes; 3)
      those with diabetes but no DS; and 4) those with both diabetes and DS. RESULTS:
      Type 2 diabetes mellitus (T2DM) was present in 13.8% of the participants; they
      presented with higher baseline rates of DS compared with the non-diabetic
      controls. During the first follow-up period, participants with DS but not
      diabetes had a 42% higher risk of all-cause mortality compared with the reference
      control group (HR=1.42; 95% CI: 1.02-1.96), while participants with diabetes but
      not DS had an 83% higher risk of death than the reference group (HR=1.83; 95% CI:
      1.19-2.80). The risk of death for those with both disorders was more than twice
      that for the reference group (HR=2.58; 95% CI: 1.55-4.29). Analyses of deaths
      from baseline to the second follow-up substantially confirmed these results.
      CONCLUSION: The prevalence rate of DS is higher in elderly people with diabetes
      and their coexistence is associated with an increased mortality risk.

PMID- 24880859
TI  - PIP2 regulates psychostimulant behaviors through its interaction with a membrane
      protein.
AB  - Phosphatidylinositol (4,5)-bisphosphate (PIP2) regulates the function of ion
      channels and transporters. Here, we demonstrate that PIP2 directly binds the
      human dopamine (DA) transporter (hDAT), a key regulator of DA homeostasis and a
      target of the psychostimulant amphetamine (AMPH). This binding occurs through
      electrostatic interactions with positively charged hDAT N-terminal residues and
      is shown to facilitate AMPH-induced, DAT-mediated DA efflux and the psychomotor
      properties of AMPH. Substitution of these residues with uncharged amino acids
      reduces hDAT-PIP2 interactions and AMPH-induced DA efflux without altering the
      hDAT physiological function of DA uptake. We evaluated the significance of this
      interaction in vivo using locomotion as a behavioral assay in Drosophila
      melanogaster. Expression of mutated hDAT with reduced PIP2 interaction in
      Drosophila DA neurons impairs AMPH-induced locomotion without altering basal
      locomotion. We present what is to our knowledge the first demonstration of how
      PIP2 interactions with a membrane protein can regulate the behaviors of complex
      organisms. 

PMID- 24880861
TI  - The association between social capital measures and self-reported health among
      Muslim majority nations.
AB  - OBJECTIVES: Much evidence suggests that social capital (e.g. networks, trust,
      organizational memberships) has a significant effect on self-reported health.
      Previous research, however, has focused primarily on Western countries. The
      current research seeks to remedy this problem by investigating the association
      between multiple social capital indicators and subjective health in a novel
      empirical setting. METHODS: The data come from the Comparative Values Survey of
      Islamic Countries (1999-2006) which consists of probabilistic samples from Muslim
      majority nations. Three-way multilevel analysis is used to examine the social
      determinants of health. RESULTS: Statistical results from hierarchical linear
      modeling shows that frequent contact with strong and intermediate ties (i.e.
      family members and friends, respectively) is significant, while interaction with
      weak ties (coworkers) has no association. General trust and trust in the central
      government are also significantly related to subjective health, as is trust in
      religious authority, albeit in an inverse way. CONCLUSIONS: This study calls for
      a more contingent view of the relationship between social capital and self
      reported health. Future research needs to take this into consideration in
      hypothesizing and testing the potential health benefits of social capital.

PMID- 24880860
TI  - Cdk5 induces constitutive activation of 5-HT6 receptors to promote neurite
      growth.
AB  - The serotonin6 receptor (5-HT6R) is a promising target for treating cognitive
      deficits of schizophrenia often linked to alterations of neuronal development.
      This receptor controls neurodevelopmental processes, but the signaling mechanisms
      involved remain poorly understood. Using a proteomic strategy, we show that 5
      HT6Rs constitutively interact with cyclin-dependent kinase 5 (Cdk5). Expression
      of 5-HT6Rs in NG108-15 cells induced neurite growth and expression of voltage
      gated Ca(2+) channels, two hallmarks of neuronal differentiation. 5-HT6R-elicited
      neurite growth was agonist independent and prevented by the 5-HT6R antagonist
      SB258585, which behaved as an inverse agonist. Moreover, it required receptor
      phosphorylation at Ser350 by Cdk5 and Cdc42 activity. Supporting a role of native
      5-HT6Rs in neuronal differentiation, neurite growth of primary neurons was
      reduced by SB258585, by silencing 5-HT6R expression or by mutating Ser350 into
      alanine. These results reveal a functional interplay between Cdk5 and a G protein
      coupled receptor to control neuronal differentiation. 

PMID- 24880862
TI  - Immediate weightbearing after Lapidus arthrodesis with external fixation.
AB  - A common surgical treatment of severe hallux abductovalgus deformity with
      coincident first ray hypermobility is metatarsal-cuneiform fusion or Lapidus
      procedure. The aim of the present study was to illustrate a reliable and novel
      method of fixation for Lapidus fusion using an external fixation device through a
      retrospective cohort investigation of consecutive patients. Twenty Lapidus
      fusions were performed in 19 patients, including 17 females (89.47%) and 2 males
      (10.53%). The mean age at surgery was 41 (range 20 to 64) years. The patients
      were evaluated clinically and radiographically pre- and postoperatively. The mean
      duration in the fixator was 12 (range 3 to 34) weeks. The mean interval to
      radiographic union was 9.2 (range 4.7 to 30.7) weeks in 18 of 20 feet (90%) and 2
      (10%) were designated as nonunion. The mean follow-up period was 37 (range 5.6 to
      211.1) weeks. The most common complication was pin tract infection in 5 patients
      (6 feet) and was treated with oral antibiotics; only 1 foot required early
      hardware removal. According to the visual analog scale, the mean patient pain
      score decreased significantly from 8.2 +/- 2.7 to 0.83 +/- 0.98 postoperatively
      (p < .001). Our results highlight that immediate weightbearing after Lapidus
      fusion with external fixation is a viable treatment option for the correction of
      severe hallux abductovalgus with associated hypermobility.

PMID- 24880863
TI  - Giant Cell Tumor of the Talus: 19-Year Follow-Up of a Patient.
AB  - Giant cell tumor in small bones is a rare condition characterized by extensive
      bony destruction and a high recurrence rate. Intralesional excision with
      curettage and autologous bone grafting has been used as a standard treatment
      method for giant cell tumor of the bones. We report the case of a 30-year-old
      female with giant cell tumor of the talar body. She was followed up for 19 years
      after intralesional curettage and autologous bone grafting treatment. 

PMID- 24880864
TI  - Plexiform fibrohistiocytic tumor of the foot: a case report.
AB  - Plexiform fibrohistiocytic tumors are rare, small, ill-defined, solitary masses
      found in the deep dermis or subcutaneous tissues. These tumors will ordinarily be
      slow-growing masses that almost solely occur in children and young adults. They
      have had a greater prevalence in the upper extremity than in the lower extremity,
      with limited reports of this lesion in the lower extremity. We report a small
      painful mass found in the central plantar heel of a 12-year-old male. 

PMID- 24880865
TI  - Hedonic capacity and schizotypy: evidence for the criterion validity of the
      ACIPS.
AB  - The association between trait hedonic capacity and schizotypal personality traits
      was examined in a two studies of independent nonclinical samples. In both
      investigations, hedonic capacity was measured using the 17-item Anticipatory and
      Consummatory Interpersonal Pleasure Scale (ACIPS). In Study One, the young
      adults' (n=1345) ACIPS scores were inversely associated with their scores on the
      Schizotypal Personality Questionnaire (SPQ). In Study Two, two groups of
      individuals identified on the basis of their scores on the Schizotypal
      Personality Questionnaire Brief-Revised (SPQ-BR) were compared in terms of their
      ACIPS responses and response patterns. Our results indicate that the high
      schizotypal subjects (n =38) and the low schizotypal subjects (n=37) differed
      significantly in terms of their mean ACIPS scores, but not in terms of their mean
      reaction times. Despite differences in study design, both investigations
      indicated an association between the No Close Friends subscale of the SPQ and the
      ACIPS total score. These findings are considered in the context of other extant
      studies of schizotypal traits and the role of anhedonia in schizotypy. Overall,
      the findings provide further evidence for the criterion validity of the ACIPS. 

PMID- 24880866
TI  - Are GATA1 mutations occurring at random in Down syndrome transient leukemia?
AB  - The somatic mutation theory of cancer proposes that cancer begins with a somatic
      mutation occurring at random in a single cell that then passes the mutation to
      its progeny, generating a clone of premalignant cells. This clone leads to a full
      malignant tumor through additional mutations and selection processes. Strikingly,
      the best-documented human model of early oncogenesis, i.e., transient
      myeloproliferative disorder followed by acute megakaryoblastic leukemia (AMKL) in
      infants with Down syndrome (DS, or trisomy 21), exhibits important discrepancies
      with the SMT. Somatic mutations in megakaryocytic precursors occur at least
      100,000 times more frequently in the GATA1 gene in fetuses with DS compared to
      the general population. Further, mutations are limited to GATA1 only; the general
      mutation rate does not significantly differ between individuals with DS and
      euploid individuals. Importantly, the mutations are also lineage-specific,
      occurring only in the megakaryocytic lineage, and proliferative anomalies of the
      megakaryocytic lineage are observed before the occurrence of GATA1 mutations.
      Thus, GATA1 mutations in fetuses with DS cannot be random events occurring in
      normal cells. Here, transcription-associated mutagenesis is proposed as the
      mechanism by which the earliest mutations of AMKL occur in DS. Transcription
      associated mutagenesis is observed in non-dividing cells when a gene is over
      expressed. The over-expression of GATA1 in the megakaryocytic lineage in DS fetal
      liver cells is proposed to be the cause of targeted GATA1 somatic mutations. As
      transcription-associated mutagenesis is a universal process, this mechanism may
      also apply to early oncogenesis in other situations, including after birth and
      following exposure to a carcinogenic agent. Thus, this hypothesis represents a
      new avenue for understanding and exploring oncogenesis in the context of DS and
      in other disease states. 

PMID- 24880867
TI  - Treatment with topical nitroglycerine may promote the healing process of diabetic
      foot ulcers.
AB  - Diabetes mellitus is one of the main problems of the health care systems of all
      societies. A vast number of diabetic patients suffer from diabetic foot ulcers
      (DFUs) some of which may lead to the amputation of the organ(s). Nitric oxide
      (NO) is an indigenous gas that is produced at various sites in the body and has
      been shown to possess important roles in wound healing. Previous studies have
      shown that not only is the production of NO decreased in diabetic patients but
      also the sensitivity of the cells of such patients to NO is dramatically reduced.
      Nitroglycerine (isosorbide dinitrate) can be employed as an effective donor of NO
      to diabetic wounds. On such a basis, we suggest a novel hypothesis that delivery
      of compensatory amounts of NO to the ulcers by the administration of topical
      nitroglycerine enhances blood flow and biochemical activity of the ulcers and
      thus promotes wound healing. 

PMID- 24880868
TI  - Detection of the food allergen celery via loop-mediated isothermal amplification
      technique.
AB  - Since 2005, celery and celery products have to be labeled according to Directive
      2003/89/EC due to their allergenic potential. In order to provide a DNA-based,
      rapid and simple detection method suitable for high-throughput analysis, a loop
      mediated isothermal amplification (LAMP) assay for the detection of celery (Apium
      graveolens) was developed. The assay was tested for specificity for celery since
      closely related species also hold food relevance. The limit of detection (LOD)
      for spiked food samples was found to be as low as 7.8 mg of dry celery powder per
      kilogram. An evaluation of different amplification and detection platforms was
      performed to show reliable detection independent from the instrument used for
      amplification (thermal cycler or heating block) and detection mechanisms (real
      time fluorescence detection, agarose gel electrophoresis or nucleic acid
      staining). The analysis of 10 commercial food samples representing diverse and
      complex food matrices, and a false-negative rate of 0% for approximately 24
      target copies or 0.08 ng celery DNA for three selected food matrices show that
      LAMP has the potential to be used as an alternative strategy for the detection of
      allergenic celery. The performance of the developed LAMP assay turned out to be
      equal or superior to the best available PCR assay for the detection of celery in
      food products.

PMID- 24880869
TI  - Effects of an iron-based fuel-borne catalyst and a diesel particle filter on
      exhaust toxicity in lung cells in vitro.
AB  - Metal-containing fuel additives catalyzing soot combustion in diesel particle
      filters are used in a widespread manner, and with the growing popularity of
      diesel vehicles, their application is expected to increase in the near future.
      Detailed investigation into how such additives affect exhaust toxicity is
      therefore necessary and has to be performed before epidemiological evidence
      points towards adverse effects of their application. The present study
      investigates how the addition of an iron-based fuel additive (Satacen(r)3, 40 ppm
      Fe) to low-sulfur diesel affects the in vitro cytotoxic, oxidative, (pro
      )inflammatory, and mutagenic activity of the exhaust of a passenger car operated
      under constant, low-load conditions by exposing a three-dimensional model of the
      human airway epithelium to complete exhaust at the air-liquid interface. We could
      show that the use of the iron catalyst without and with filter technology has
      positive as well as negative effects on exhaust toxicity compared to exhaust with
      no additives: it decreases the oxidative and, compared to a non-catalyzed diesel
      particle filter, the mutagenic potential of diesel exhaust, but increases (pro
      )inflammatory effects. The presence of a diesel particle filter also influences
      the impact of Satacen(r)3 on exhaust toxicity, and the proper choice of the
      filter type to be used is of importance with regards to exhaust toxicity. Figure
      ?. 

PMID- 24880870
TI  - Tunable stringency aptamer selection and gold nanoparticle assay for detection of
      cortisol.
AB  - The first-known aptamer for the stress biomarker cortisol was selected using a
      tunable stringency magnetic bead selection strategy. The capture DNA probe
      immobilized on the beads was systematically lengthened to increase the number of
      bases bound to the complementary pool primer regions following selection
      enrichment. This resulted in a single sequence (15-1) dominating the final round
      15 pool, where the same sequence was the second-highest copy number candidate in
      the enriched pool with the shorter capture DNA probe (round 13). A thorough
      analysis of the next-generation sequencing results showed that a high copy number
      may only correlate with enhanced affinity under certain stringency and enrichment
      conditions, in contrast with prior published reports. Aptamer 15-1 demonstrated
      enhanced binding to cortisol (K(d) = 6.9 +/- 2.8 MUM by equilibrium dialysis;
      16.1 +/- 0.6 MUM by microscale thermophoresis) when compared with the top
      sequence from round 13 and the negative control progesterone. Whereas most
      aptamer selections terminate at the selection round demonstrating the highest
      enrichment, this work shows that extending the selection with higher stringency
      conditions leads to lower amounts eluted by the target but higher copy numbers of
      a sequence with enhanced binding. The structure-switching aptamer was applied to
      a gold nanoparticle assay in buffer and was shown to discriminate between
      cortisol and two other stress biomarkers, norepinephrine and epinephrine, and a
      structurally analogous biomarker of liver dysfunction, cholic acid. We believe
      this approach enhances aptamer selection and serves as proof-of-principle work
      toward development of point-of-care diagnostics for medical, combat, or
      bioterrorism targets.

PMID- 24880871
TI  - Detection of the 35S promoter in transgenic maize via various isothermal
      amplification techniques: a practical approach.
AB  - In 2003 the European Commission introduced a 0.9% threshold for food and feed
      products containing genetically modified organism (GMO)-derived components. For
      commodities containing GMO contents higher than this threshold, labelling is
      mandatory. To provide a DNA-based rapid and simple detection method suitable for
      high-throughput screening of GMOs, several isothermal amplification approaches
      for the 35S promoter were tested: strand displacement amplification, nicking
      enzyme amplification reaction, rolling circle amplification, loop-mediated
      isothermal amplification (LAMP) and helicase-dependent amplification (HDA). The
      assays developed were tested for specificity in order to distinguish between
      samples containing genetically modified (GM) maize and non-GM maize. For those
      assays capable of this discrimination, tests were performed to determine the
      lower limit of detection. A false-negative rate was determined to rule out
      whether GMO-positive samples were incorrectly classified as GMO-negative. A
      robustness test was performed to show reliable detection independent from the
      instrument used for amplification. The analysis of three GM maize lines showed
      that only LAMP and HDA were able to differentiate between the GMOs MON810, NK603,
      and Bt11 and non-GM maize. Furthermore, with the HDA assay it was possible to
      realize a detection limit as low as 0.5%. A false-negative rate of only 5% for 1%
      GM maize for all three maize lines shows that HDA has the potential to be used as
      an alternative strategy for the detection of transgenic maize. All results
      obtained with the LAMP and HDA assays were compared with the results obtained
      with a previously reported real-time PCR assay for the 35S promoter in transgenic
      maize. This study presents two new screening assays for detection of the 35S
      promoter in transgenic maize by applying the isothermal amplification approaches
      HDA and LAMP.

PMID- 24880872
TI  - Increased phosphatidylcholine (16:0/16:0) in the folliculus lymphaticus of
      Warthin tumor.
AB  - Warthin tumor (War-T), the second most common benign salivary gland tumor,
      consists mainly of neoplastic epithelium and lymphoid stroma. Some proteins and
      genes thought to be involved in War-T were evaluated by molecular biology and
      immunology. However, lipids as an important component of many tumor cells have
      not been well studied in War-T. To elucidate the molecular biology and
      pathogenesis of War-T, we investigated the visualized distribution of
      phosphatidylcholines (PCs) by imaging mass spectrometry (IMS). In our IMS
      analysis of a typical case, 10 signals were significantly different in intensity
      (p < 0.01) between the War-T and non-tumor (Non-T) regions. Five specific PCs
      were frequently found in the War-T regions of all of the samples: [PC (16:0/16:0)
      + K](+) (m/z 772.5), [PC (16:0/20:4) + K](+) (m/z 820.5), [PC (16:0/20:3) + K](+)
      (m/z 822.5), [PC (18:2/20:4) + K](+) (m/z 844.5), and [PC (18:0/20:5) + K](+)
      (m/z 846.5). PC (16:0/16:0) was increased specifically in the folliculus
      lymphaticus of War-T lymphoid stroma, suggesting a different metabolism.
      Localization of PC (16:0/16:0) might reflect inflammation activity participating
      in the pathogenesis of War-T. Thus, our IMS analysis revealed the profile of PCs
      specific to the War-T region. The molecules identified in our study provide
      important information for further studies of War-T pathogenesis. 

PMID- 24880874
TI  - Recent progress in graphene-material-based optical sensors.
AB  - Graphene material has been widely used for optical sensors owing to its excellent
      properties, including high-energy transfer efficiency, large surface area, and
      great biocompatibility. Different analytes such as nucleic acids, proteins, and
      small molecules can be detected by graphene-material-based optical sensors. This
      review provides a comprehensive discussion of graphene-material-based optical
      sensors focusing on detection mechanisms and biosensor designs. Challenges and
      future perspectives for graphene-material-based optical sensors are also
      presented. 

PMID- 24880873
TI  - Multiplexed microfluidic enzyme assays for simultaneous detection of lipolysis
      products from adipocytes.
AB  - Microfluidics has enabled new cell biology experiments. Incorporating chemical
      monitoring of cellular secretion into chips offers the potential to increase
      information content and utility of such systems. In this work, an integrated,
      multilayer polydimethylsiloxane microfluidic chip was developed to simultaneously
      measure fatty acids and glycerol secreted from cultured adipocytes on chip in
      near real time. Approximately 48,000 adipocytes were loaded into a cell chamber
      in a reversibly sealed chip. Cells were perfused at 0.75 MUL/min. Cell perfusate
      was split and directed to separate, continuously operating fluorescent enzyme
      assay channel networks. The fluorescent assay products were detected
      simultaneously near the outlet of the chip. The fatty acid and glycerol assays
      had linear dynamic ranges of 150 and 110 MUM and limit of detection (LOD) of 6
      and 5 MUM, respectively. Surface modifications including pretreatment with sodium
      dodecyl sulfate were utilized to prevent adsorption of fatty acids to the chip
      surface. Using the chip, basal fatty acid and glycerol concentrations ranged from
      0.18 to 0.7 nmol * 10(6) cell(-1) min(-1) and from 0.23 to 0.85 nmol * 10(6)
      cell(-1) min(-1), respectively. Using valves built into the chip, the perfusion
      solution was switched to add 20 MUM isoproterenol, a beta-adrenergic agonist,
      which stimulates the release of glycerol and fatty acids in adipocytes. This
      manipulation resulted in a rapid and stable 1.5- to 6.0-fold increase of non
      esterified fatty acid (NEFA) and glycerol. The ratio of NEFA:glycerol released
      increased with adipocyte age. These experiments illustrate the potential for
      performing multiple real-time assays on cells in culture using microfluidic
      devices.

PMID- 24880875
TI  - Raman spectroscopic detection and identification of Burkholderia mallei and
      Burkholderia pseudomallei in feedstuff.
AB  - Burkholderia mallei (the etiologic agent of glanders in equines and rarely
      humans) and Burkholderia pseudomallei, causing melioidosis in humans and animals,
      are designated category B biothreat agents. The intrinsically high resistance of
      both agents to many antibiotics, their potential use as bioweapons, and their low
      infectious dose, necessitate the need for rapid and accurate detection methods.
      Current methods to identify these organisms may require up to 1 week, as they
      rely on phenotypic characteristics and an extensive set of biochemical reactions.
      In this study, Raman microspectroscopy, a cultivation-independent typing
      technique for single bacterial cells with the potential for being a rapid point
      of-care analysis system, is evaluated to identify and differentiate B. mallei and
      B. pseudomallei within hours. Here, not only broth-cultured microbes but also
      bacteria isolated out of pelleted animal feedstuff were taken into account. A
      database of Raman spectra allowed a calculation of classification functions,
      which were trained to differentiate Raman spectra of not only both pathogens but
      also of five further Burkholderia spp. and four species of the closely related
      genus Pseudomonas. The developed two-stage classification system comprising two
      support vector machine (SVM) classifiers was then challenged by a test set of 11
      samples to simulate the case of a real-world-scenario, when "unknown samples" are
      to be identified. In the end, all test set samples were identified correctly,
      even if the contained bacterial strains were not incorporated in the database
      before or were isolated out of animal feedstuff. Specifically, the five test
      samples bearing B. mallei and B. pseudomallei were correctly identified on
      species level with accuracies between 93.9 and 98.7%. The sample analysis itself
      requires no biomass enrichment step prior to the analysis and can be performed
      under biosafety level 1 (BSL 1) conditions after inactivating the bacteria with
      formaldehyde.

PMID- 24880876
TI  - Single-cell western blotting.
AB  - To measure cell-to-cell variation in protein-mediated functions, we developed an
      approach to conduct ~10(3) concurrent single-cell western blots (scWesterns) in
      ~4 h. A microscope slide supporting a 30-MUm-thick photoactive polyacrylamide gel
      enables western blotting: settling of single cells into microwells, lysis in
      situ, gel electrophoresis, photoinitiated blotting to immobilize proteins and
      antibody probing. We applied this scWestern method to monitor single-cell
      differentiation of rat neural stem cells and responses to mitogen stimulation.
      The scWestern quantified target proteins even with off-target antibody binding,
      multiplexed to 11 protein targets per single cell with detection thresholds of
      <30,000 molecules, and supported analyses of low starting cell numbers (~200)
      when integrated with FACS. The scWestern overcomes limitations of antibody
      fidelity and sensitivity in other single-cell protein analysis methods and
      constitutes a versatile tool for the study of complex cell populations at single
      cell resolution. 

PMID- 24880878
TI  - Sudden unexpected death in the setting of undiagnosed Graves' disease.
AB  - Graves' disease is the most common cause of hyperthyroidism and is classically
      characterized by the clinical triad of diffuse toxic goiter, infiltrative
      ophthalmopathy with exophthalmos and an infiltrative dermopathy. While the name
      of the Irishman Robert Graves has received the eponymous honor, the first
      description of the condition in the English language can be attributed to the
      Englishman Caleb Perry, while in continental Europe the entity in name once
      honored Karl von Basedow. We present the case of a previously well 43 year old
      woman who presented in supraventricular tachycardia and acute pulmonary edema and
      died despite treatment and without a diagnosis for cause of death. At autopsy the
      significant positive macroscopic findings were confined to the lungs (acute
      pulmonary edema) and thyroid (diffusely enlarged). Histology revealed features
      typical of Graves' disease while post mortem thyroid function tests supported a
      diagnosis of thyrotoxic crisis in the setting of undiagnosed Graves' disease. 

PMID- 24880877
TI  - idTracker: tracking individuals in a group by automatic identification of
      unmarked animals.
AB  - Animals in groups touch each other, move in paths that cross, and interact in
      complex ways. Current video tracking methods sometimes switch identities of
      unmarked individuals during these interactions. These errors propagate and result
      in random assignments after a few minutes unless manually corrected. We present
      idTracker, a multitracking algorithm that extracts a characteristic fingerprint
      from each animal in a video recording of a group. It then uses these fingerprints
      to identify every individual throughout the video. Tracking by identification
      prevents propagation of errors, and the correct identities can be maintained
      indefinitely. idTracker distinguishes animals even when humans cannot, such as
      for size-matched siblings, and reidentifies animals after they temporarily
      disappear from view or across different videos. It is robust, easy to use and
      general. We tested it on fish (Danio rerio and Oryzias latipes), flies
      (Drosophila melanogaster), ants (Messor structor) and mice (Mus musculus).

PMID- 24880879
TI  - Point-counter-point debate: the association between recombinant human bone
      morphogenetic protein utilization and complications in spine surgery.
AB  - Bone morphogenetic proteins (BMPs) have been utilized in spine surgery for over
      10 years as a bone graft substitute. Potential BMP-related adverse effects
      including retrograde ejaculation and heterotopic neuroforaminal bone formation
      have been described. Additionally, some studies have suggested an association
      between BMP and cancer. Inconsistencies exist in the published spine literature
      with regards to the incidence and association of complications with BMP
      utilization. In a point-counterpoint format, this article discusses the current
      evidence concerning the relationship between the utilization of BMP in spinal
      fusion and the risk of cancer, retrograde ejaculation (RE), neuroforaminal bone
      formation, and its role in anterior cervical spine surgery and adolescents. 

PMID- 24880880
TI  - Characterization and correction of eddy-current artifacts in unipolar and bipolar
      diffusion sequences using magnetic field monitoring.
AB  - Diffusion tensor imaging (DTI) of moving organs is gaining increasing attention
      but robust performance requires sequence modifications and dedicated correction
      methods to account for system imperfections. In this study, eddy currents in the
      "unipolar" Stejskal-Tanner and the velocity-compensated "bipolar" spin-echo
      diffusion sequences were investigated and corrected for using a magnetic field
      monitoring approach in combination with higher-order image reconstruction. From
      the field-camera measurements, increased levels of second-order eddy currents
      were quantified in the unipolar sequence relative to the bipolar diffusion
      sequence while zeroth and linear orders were found to be similar between both
      sequences. Second-order image reconstruction based on field-monitoring data
      resulted in reduced spatial misalignment artifacts and residual displacements of
      less than 0.43 mm and 0.29 mm (in the unipolar and bipolar sequences,
      respectively) after second-order eddy-current correction. Results demonstrate the
      need for second-order correction in unipolar encoding schemes but also show that
      bipolar sequences benefit from second-order reconstruction to correct for
      incomplete intrinsic cancellation of eddy-currents.

PMID- 24880881
TI  - Efficient polarization transfer between spin-1/2 and 14N nuclei in solid-state
      MAS NMR spectroscopy.
AB  - Polarization transfer between spin-1/2 nuclei and quadrupolar spin-1 nuclei such
      as (14)N in solid-state NMR is severely challenged by the typical presence of
      large quadrupole coupling interactions. This has effectively prevented the use of
      the abundant (14)N spin as a probe to structural information and its use as an
      element in multi-dimensional solid-state NMR correlation experiments for
      assignment and structural characterization. In turn, this has been a contributing
      factor to the extensive use of isotope labeling in biological solid-state NMR,
      where (14)N is replaced with (15)N. The alternative strategy of using the
      abundant (14)N spins calls for methods enabling efficient polarization transfer
      between (14)N and its binding partners. This work demonstrates that the recently
      introduced (RESPIRATION)CP transfer method can be optimized to achieve efficient
      (1)H <->(14)N polarization transfer under magic angle spinning conditions. The
      method is demonstrated numerically and experimentally on powder samples of NH4NO3
      and L-alanine.

PMID- 24880882
TI  - Effect of transient cerebral ischemia on the expression of receptor for advanced
      glycation end products (RAGE) in the gerbil hippocampus proper.
AB  - The receptor for advanced glycation end products (RAGE) is a multi-ligand
      receptor of the immunoglobulin superfamily that has been implicated in multiple
      neuronal and inflammatory stress processes. In this study, we examined changes in
      RAGE immunoreactivity and its protein levels in the gerbil hippocampus (CA1-3
      regions) after 5 min of transient global cerebral ischemia. The ischemic
      hippocampus was stained with cresyl violet, neuronal nuclei (a neuron-specific
      soluble nuclear antigen) antibody and Fluoro-Jade B (a marker for neuronal
      degeneration). 5 days after ischemia-reperfusion, delayed neuronal death occurred
      in the stratum pyramidale of the CA1 region. RAGE immunoreactivity was not
      detected in any regions of the CA1-3 regions of the sham-group; the
      immunoreactivity was markedly increased only in the CA1 region from 3 days after
      ischemia-reperfusion. On the other hand, RAGE immunoreactivity was newly
      expressed in astrocytes, not in microglia. Western blot analysis showed that RAGE
      protein level was highest at 5 days post-ischemia. In brief, both the RAGE
      immunoreactivity and protein level were distinctively increased in astrocytes in
      the ischemic CA1 region from 3 days after transient cerebral ischemia. These
      results indicate that the increase of RAGE expression in astrocytes after
      ischemia-reperfusion may be related to the ischemia-caused activation of
      astrocytes in the ischemic CA1 region. 

PMID- 24880883
TI  - Effect of vitrification versus slow freezing of human day 3 embryos on beta-hCG
      levels.
AB  - PURPOSE: The study was designed to investigate the effect of vitrification and
      slow freezing for the cryopreservation of human day 3 embryos on serum beta-hCG
      levels in pregnancies established after frozen embryo transfer (FET). METHODS: Of
      the 1384 FET cycles initiated, 1131 embryo transfers met study criteria and
      assigned to one of two groups: 797 slow-freezing embryo transfers or 334
      vitrified embryo transfers. Median values of beta-hCG and outcome of all
      pregnancies were compared between the two groups. Predictive values of serum beta
      hCG on day 12 after embryo transfer for establishing ongoing pregnancy and
      pregnancy failure were determined by receiver operating characteristic (ROC)
      curve analysis. RESULTS: In the slow-freezing group, 383 ongoing pregnancies
      occurred (48.1 %), and transfers of vitrified embryos resulted in 154 pregnancies
      (46.1 %). Median beta-hCG values (279.2 IU/L) for ongoing pregnancies after
      transfer of vitrified embryos were significantly lower than that of slow frozen
      embryos (320.5 IU/L). The median values of beta-hCG for singleton in the two
      groups was statistically significant (P <0.05). For slow-freezing embryo
      transfers, the cut-off value of beta-hCG in predicting ongoing pregnancy was 147
      IU/L (sensitivity 88.3 %, specificity 80.7 %). For vitrified embryo transfers,
      the value was 135 IU/L (sensitivity 84.4 %, specificity 76.3 %). CONCLUSIONS: Day
      12 beta-hCG levels after FET are significantly affected by the methods of embryo
      cryopreservation for ongoing pregnancies. Furthermore, when using beta-hCG cut
      off value to assess pregnancy outcome, the cryopreservation methods should be
      taken into account.

PMID- 24880884
TI  - Development of the Internet addiction scale based on the Internet Gaming Disorder
      criteria suggested in DSM-5.
AB  - This study was conducted to develop and validate a standardized self-diagnostic
      Internet addiction (IA) scale based on the diagnosis criteria for Internet Gaming
      Disorder (IGD) in the Diagnostic and Statistical Manual of Mental Disorder, 5th
      edition (DSM-5). Items based on the IGD diagnosis criteria were developed using
      items of the previous Internet addiction scales. Data were collected from a
      community sample. The data were divided into two sets, and confirmatory factor
      analysis (CFA) was performed repeatedly. The model was modified after discussion
      with professionals based on the first CFA results, after which the second CFA was
      performed. The internal consistency reliability was generally good. The items
      that showed significantly low correlation values based on the item-total
      correlation of each factor were excluded. After the first CFA was performed, some
      factors and items were excluded. Seven factors and 26 items were prepared for the
      final model. The second CFA results showed good general factor loading, Squared
      Multiple Correlation (SMC) and model fit. The model fit of the final model was
      good, but some factors were very highly correlated. It is recommended that some
      of the factors be refined through further studies. 

PMID- 24880885
TI  - The contemporary management of penetrating splenic injury.
AB  - INTRODUCTION: Selective non-operative management (NOM) is standard of care for
      clinically stable patients with blunt splenic trauma and expectant management
      approaches are increasingly utilised in penetrating abdominal trauma, including
      in the setting of solid organ injury. Despite this evolution of clinical
      practice, little is known about the safety and efficacy of NOM in penetrating
      splenic injury. METHODS: Trauma registry and medical record review identified all
      consecutive patients presenting to LAC+USC Medical Center with penetrating
      splenic injury between January 2001 and December 2011. Associated injuries,
      incidence and nature of operative intervention, local and systemic complications
      and mortality were determined. RESULTS: During the study period, 225 patients
      experienced penetrating splenic trauma. The majority (187/225, 83%) underwent
      emergent laparotomy. Thirty-eight clinically stable patients underwent a
      deliberate trial of NOM and 24/38 (63%) were ultimately managed without
      laparotomy. Amongst patients failing NOM, 3/14 (21%) underwent splenectomy while
      an additional 6/14 (42%) had splenorrhaphy. Hollow viscus injury (HVI) occurred
      in 21% of all patients failing NOM. Forty percent of all NOM patients had
      diaphragmatic injury (DI). All patients undergoing delayed laparotomy for HVI or
      a splenic procedure presented symptomatically within 24h of the initial injury.
      No deaths occurred in patients undergoing NOM. CONCLUSIONS: Although the vast
      majority of penetrating splenic trauma requires urgent operative management, a
      group of patients does present without haemodynamic instability, peritonitis or
      radiologic evidence of hollow viscus injury. Management of these patients is
      complicated as over half may remain clinically stable and can avoid laparotomy,
      making them potential candidates for a trial of NOM. HVI is responsible for NOM
      failure in up to a fifth of these cases and typically presents within 24h of
      injury. Delayed laparotomy, within this limited time period, did not appear to
      increase mortality nor preclude successful splenic salvage. In clinically stable
      patients, diagnostic laparoscopy remains essential to evaluate and repair occult
      DI. As NOM for penetrating abdominal trauma becomes more common, multi-centre
      data is needed to more accurately define the principles of patient selection and
      the limitations and consequences of this approach in the setting of splenic
      injury.

PMID- 24880886
TI  - Mid-term results after treatment of intertrochanteric femoral fractures with
      percutaneous compression plate (PCCP).
AB  - BACKGROUND: With the ageing of the population, intertrochanteric femoral fracture
      is associated with increased morbidity. There is continuing controversy over the
      best treatment for the injury, and the choice of internal fixation method has
      been a focus of dispute. The purpose of this study was to evaluate the results of
      these fractures being treated with the percutaneous compression plate (PCCP)
      technique. METHODS: From March 2009 to May 2012, 154 patients with
      intertrochanteric femoral fractures were treated using the PCCP method. Forty-one
      patients were excluded from the study. According to the AO classification, the
      remaining 113 fractures were classified as 35 cases of 31A1 fractures, 59 cases
      of 31A2 fractures, and 19 cases of 31A3 fractures. The clinical data and imaging
      results were retrospectively analysed. RESULTS: The mean operation time was 42.0
      (range, 25-82) min, the mean intraoperative blood loss was 40.5 (range, 10-100)
      ml, and the mean hospital stay was 8.6 (range, 3-18) days. One patient died of
      renal failure in the perioperative period. Twelve patients died during the 12
      months after surgery. The remaining 100 patients were followed-up for 12-36
      months and healed their fractures except one, whose neck screw cut out from the
      femoral neck after 1 postoperative month and resulting in a revision to a
      hemiarthroplasty. The mean time to bone healing was 12.6 (range, 6-23) weeks.
      Sixteen patients had pain. There were 13 major device-related complications,
      including 5 cases of coxa vara, 4 cases of fracture collapse, 2 cases of head
      penetration, and 2 cases of fracture collapse combined with head penetration. At
      the time of the last follow-up, 81 patients had regained a pre-injury level of
      function. The median Harris hip score was 89 points. The median Parker-Palmer
      score was 7 points. Patients with poor quality of reduction and bad positioning
      of neck screw were more likely to suffer complications (p<0.05). CONCLUSION: The
      results suggest that the PCCP is an effective and safe method in the treatment of
      all types of intertrochanteric femoral fractures, but good fracture reduction and
      ideal positioning of the neck screw are prerequisites for the success of the
      device.

PMID- 24880887
TI  - Recurrent ovarian cancer with multiple lymph nodes metastases successfully
      treated with lymphadenectomy as secondary cytoreductive surgery: A case report.
AB  - INTRODUCTION: Occasionally, lymph node metastases represent the only component at
      the time of recurrence of ovarian cancer. Here we report the case of a 78-year
      old Japanese female who underwent successful surgery for recurrent ovarian cancer
      with multiple lymph node metastases. PRESENTATION OF CASE: The patient was
      referred to our institution with recurrent disease accompanied by chemoresistant
      multiple retroperitoneal lymph node metastases five years after the initial
      therapy for stage IIIc serous adenocarcinoma of the ovary. Positron emission
      tomography/computed tomography (PET/CT) revealed the involvement of two para
      aortic nodes and two pelvic nodes, with no other positive site. The patient
      underwent systematic para-aortic and pelvic lymphadenectomy, and the metastatic
      nodes were completely resected. Histopathological examination revealed metastatic
      high-grade adenocarcinoma in four of 63 dissected lymph node specimens. The
      patient has been in clinical remission for over four years without any further
      additional therapies. DISCUSSION: In our case, the metastatic nodes predicted by
      PET/CT completely corresponded to the actual metastatic nodes; however, PET/CT
      often fails to identify microscopic disease in pathological positive nodes. We
      cannot reliably predict whether lymph node metastasis will persist in the limited
      range. Therefore, systematic lymphadenectomy with therapeutic intent should be
      performed, although it does not always mean that we remove all cancer cells.
      CONCLUSION: The findings from this case suggest that, even if used as secondary
      cytoreductive surgery in the context of a recurrent disease, systematic aortic
      and pelvic node dissection might sometimes contribute to the control if not cure
      of ovarian cancer.

PMID- 24880890
TI  - Integrating medical students as covert observers in the evaluation of hand
      hygiene compliance.

PMID- 24880888
TI  - Prophylactic use of Lactobacillus acidophilus/Bifidobacterium infantis probiotics
      and outcome in very low birth weight infants.
AB  - OBJECTIVE: To evaluate outcome data in an observational cohort of very low birth
      weight infants of the German Neonatal Network stratified to prophylactic use of
      Lactobacillus acidophilus/Bifidobacterium infantis probiotics. STUDY DESIGN:
      Within the observational period (September 1, 2010, until December 31, 2012,
      n=5351 infants) study centers were categorized into 3 groups based on their
      choice of Lactobacillus acidophilus/Bifidobacterium infantis use: (1) no
      prophylactic use (12 centers); (2 a/b) change of strategy nonuser to user during
      observational period (13 centers); and (3) use before start of observation (21
      centers). Primary outcome data of all eligible infants were determined according
      to center-specific strategy. RESULTS: The use of probiotics was associated with a
      reduced risk for necrotizing enterocolitis surgery (group 1 vs group 3: 4.2 vs
      2.6%, P=.028; change of strategy: 6.2 vs 4.0%, P<.001), any abdominal surgery,
      and hospital mortality. Infants treated with probiotics had improved weight
      gain/day, and probiotics had no effect on the risk of blood-culture confirmed
      sepsis. In a multivariable logistic regression analysis, probiotics were
      protective for necrotizing enterocolitis surgery (OR 0.58, 95% CI 0.37-0.91;
      P=.017), any abdominal surgery (OR 0.7, 95% CI 0.51-0.95; P=.02), and the
      combined outcome abdominal surgery and/or death (OR 0.43; 95% CI 0.33-0.56;
      P<.001). CONCLUSIONS: Our observational data support the use of Lactobacillus
      acidophilus/Bifidobacterium infantis probiotics to reduce the risk for
      gastrointestinal morbidity but not sepsis in very low birth weight infants.

PMID- 24880889
TI  - Augmenting ureagenesis in patients with partial carbamyl phosphate synthetase 1
      deficiency with N-carbamyl-L-glutamate.
AB  - Identical studies using stable isotopes were performed before and after a 3-day
      trial of oral N-carbamyl-l-glutamate (NCG) in 5 subjects with late-onset carbamyl
      phosphate synthetase deficiency. NCG augmented ureagenesis and decreased plasma
      ammonia in 4 of 5 subjects. There was marked improvement in nitrogen metabolism
      with long-term NCG administration in 1 subject. 

PMID- 24880891
TI  - Parametric modeling of the intervertebral disc space in 3D: application to CT
      images of the lumbar spine.
AB  - Gradual degeneration of intervertebral discs of the lumbar spine is one of the
      most common causes of low back pain. Although conservative treatment for low back
      pain may provide relief to most individuals, surgical intervention may be
      required for individuals with significant continuing symptoms, which is usually
      performed by replacing the degenerated intervertebral disc with an artificial
      implant. For designing implants with good bone contact and continuous force
      distribution, the morphology of the intervertebral disc space and vertebral body
      endplates is of considerable importance. In this study, we propose a method for
      parametric modeling of the intervertebral disc space in three dimensions (3D) and
      show its application to computed tomography (CT) images of the lumbar spine. The
      initial 3D model of the intervertebral disc space is generated according to the
      superquadric approach and therefore represented by a truncated elliptical cone,
      which is initialized by parameters obtained from 3D models of adjacent vertebral
      bodies. In an optimization procedure, the 3D model of the intervertebral disc
      space is incrementally deformed by adding parameters that provide a more detailed
      morphometric description of the observed shape, and aligned to the observed
      intervertebral disc space in the 3D image. By applying the proposed method to CT
      images of 20 lumbar spines, the shape and pose of each of the 100 intervertebral
      disc spaces were represented by a 3D parametric model. The resulting mean (+/
      standard deviation) accuracy of modeling was 1.06+/-0.98mm in terms of radial
      Euclidean distance against manually defined ground truth points, with the
      corresponding success rate of 93% (i.e. 93 out of 100 intervertebral disc spaces
      were modeled successfully). As the resulting 3D models provide a description of
      the shape of intervertebral disc spaces in a complete parametric form,
      morphometric analysis was straightforwardly enabled and allowed the computation
      of the corresponding heights, widths and volumes, as well as of other geometric
      features that in detail describe the shape of intervertebral disc spaces. 

PMID- 24880892
TI  - Examining the multifactorial nature of a cognitive process using Bayesian brain
      behavior modeling.
AB  - Establishing relationships among brain structures and cognitive functions is a
      central task in cognitive neuroscience. Existing methods to establish
      associations among a set of function variables and a set of brain regions, such
      as dissociation logic and conjunction analysis, are hypothesis-driven. We propose
      a new data-driven approach to structure-function association analysis. We
      validated it by analyzing a simulated atrophy study. We applied the proposed
      method to a study of aging and dementia. We found that the most significant age
      related and dementia-related volume reductions were in the hippocampal formation
      and the supramarginal gyrus, respectively. These findings suggest a multi
      component brain-aging model. 

PMID- 24880894
TI  - Biosynthesis of ethyl (S)-4-chloro-3-hydroxybutanoate by NADH-dependent reductase
      from E. coli CCZU-Y10 discovered by genome data mining using mannitol as
      cosubstrate.
AB  - The reductase (PgCR) from recombinant Escherichia coli CCZU-Y10 displayed high
      reductase activity and excellent stereoselectivity for the reduction of ethyl 4
      chloro-3-oxobutanoate (COBE) into ethyl (S)-4-chloro-3-hydroxybutanoate ((S)
      CHBE). To efficiently synthesize (S)-CHBE (>99 % enantiomeric excess (ee)), the
      highly stereoselective bioreduction of COBE into (S)-CHBE with the whole cells of
      E. coli CCZU-Y10 was successfully demonstrated in a dibutyl phthalate-water
      biphasic system. The appropriate ratio of the organic phase to water phase was
      1:1 (v/v). The optimum reaction temperature, reaction pH, cosubstrate, NAD(+),
      and cell dosage of the biotransformation of 100 mM COBE in this biphasic system
      were 30  degrees C, 7.0, mannitol (2.5 mmol/mmol COBE), 0.1 MUmol/(mmol COBE),
      and 0.1 g (wet weight)/mL, respectively. Moreover, COBE at a high concentration
      of (1,000 mM) could be asymmetrically reduced to (S)-CHBE in a high yield (99.0
      %) and high enantiometric excess value (>99 % ee). Significantly, E. coli CCZU
      Y10 shows high potential in the industrial production of (S)-CHBE (>99 % ee).

PMID- 24880893
TI  - Malondialdehyde-acetaldehyde (MAA) adducted proteins bind to scavenger receptor A
      in airway epithelial cells.
AB  - Co-exposure to cigarette smoke and ethanol generates malondialdehyde and
      acetaldehyde, which can subsequently lead to the formation of aldehyde-adducted
      proteins. We have previously shown that exposure of bronchial epithelial cells to
      malondialdehyde-acetaldehyde (MAA) adducted protein increases protein kinase C
      (PKC) activity and proinflammatory cytokine release. A specific ligand to
      scavenger receptor A (SRA), fucoidan, blocks this effect. We hypothesized that
      MAA-adducted protein binds to bronchial epithelial cells via SRA. Human bronchial
      epithelial cells (BEAS-2B) were exposed to MAA-adducted protein (either bovine
      serum albumin [BSA-MAA] or surfactant protein D [SPD-MAA]) and SRA examined using
      confocal microscopy, fluorescent activated cell sorting (FACS), and
      immunoprecipitation. Differentiated mouse tracheal epithelial cells (MTEC)
      cultured by air-liquid interface were assayed for MAA-stimulated PKC activity and
      keratinocyte-derived chemokine (KC) release. Specific cell surface membrane dye
      co-localized with upregulated SRA after exposure to MAA for 3-7 min and subsided
      by 20 min. Likewise, MAA-adducted protein co-localized to SRA from 3 to 7 min
      with a subsequent internalization of MAA by 10 min. These results were confirmed
      using FACS analysis and revealed a reduced mean fluorescence of SRA after 3 min.
      Furthermore, increased amounts of MAA-adducted protein could be detected by
      Western blot in immunoprecipitated SRA samples after 3 min treatment with MAA.
      MAA stimulated PKCepsilon-mediated KC release in wild type, but not SRA knockout
      mice. These data demonstrate that aldehyde-adducted proteins in the lungs rapidly
      bind to SRA and internalize this receptor prior to the MAA-adducted protein
      stimulation of PKC-dependent inflammatory cytokine release in airway epithelium.

PMID- 24880895
TI  - Cystic fibrosis: need for mass deployable screening methods.
AB  - Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the
      cystic fibrosis transmembrane conductance regulator (CFTR) gene. CFTR is a member
      of the adenosine triphosphate (ATP)-binding cassette superfamily of proteins and
      it functions as a chloride channel. CFTR largely controls the working of
      epithelial cells of the airways, the gastrointestinal tract, exocrine glands, and
      genitourinary system. Cystic fibrosis is responsible for severe chronic pulmonary
      disorders in children. Other maladies in the spectrum of this life-limiting
      disorder include nasal polyposis, pansinusitis, rectal prolapse, pancreatitis,
      cholelithiasis, insulin-dependent hyperglycemia, and cirrhosis. This review
      summarizes the recent state of art in the field of cystic fibrosis diagnostic
      methods with the help of CF literature published so far and proposes new research
      domains in the field of cystic fibrosis diagnosis. 

PMID- 24880896
TI  - Lack of vitamin D receptor causes stress-induced premature senescence in vascular
      smooth muscle cells through enhanced local angiotensin-II signals.
AB  - OBJECTIVES: The inhibition of the renal renin-angiotensin system by the active
      form of vitamin D contributes to the cardiovascular health benefits of a normal
      vitamin D status. Local production of angiotensin-II in the vascular wall is a
      potent mediator of oxidative stress, prompting premature senescence. Herein, our
      objective was to examine the impact of defective vitamin D signalling on local
      angiotensin-II levels and arterial health. METHODS: Primary cultures of aortic
      vascular smooth muscle cells (VSMC) from wild-type and vitamin D receptor
      knockout (VDRKO) mice were used for the assessment of cell growth, angiotensin-II
      and superoxide anion production and expression levels of cathepsin D, angiotensin
      II type 1 receptor and p57(Kip2). The in vitro findings were confirmed
      histologically in aortas from wild-type and VDRKO mice. RESULTS: VSMC from VDRKO
      mice produced more angiotensin-II in culture, and elicited higher levels of
      cathepsin D, an enzyme with renin-like activity, and angiotensin-II type 1
      receptor, than wild-type mice. Accordingly, VDRKO VSMC showed higher
      intracellular superoxide anion production, which could be suppressed by cathepsin
      D, angiotensin-II type 1 receptor or NADPH oxidase antagonists. VDRKO cells
      presented higher levels of p57(Kip2), impaired proliferation and premature
      senescence, all of them blunted upon inhibition of angiotensin-II signalling. In
      vivo studies confirmed higher levels of cathepsin D, angiotensin-II type 1
      receptor and p57(Kip2) in aortas from VDRKO mice. CONCLUSION: The beneficial
      effects of active vitamin D in vascular health could be a result of the
      attenuation of local production of angiotensin-II and downstream free radicals,
      thus preventing the premature senescence of VSMC.

PMID- 24880897
TI  - Low dose aspirin is associated with plasma chemerin levels and may reduce adipose
      tissue inflammation.
AB  - Chemerin is a peptide chemoattractant for macrophages and an adipokine regulating
      adipocyte differentiation and metabolism. Plasma chemerin is increased in chronic
      inflammatory diseases and in obesity. As inflammation and obesity are risk
      factors for coronary artery disease (CAD), we investigated possible associations
      of plasma chemerin with inflammatory markers and atherosclerosis in a CAD case
      control study (n=470). Chemerin levels were associated with C-reactive protein,
      BMI and LDL levels, and negatively associated with HDL levels. Mean plasma
      chemerin levels were similar in controls and CAD patients but significantly
      higher in CAD patients not taking low dose aspirin. To investigate the mechanism
      of chemerin reduction by aspirin, we analyzed chemerin expression in hepatocytes
      and adipocytes treated with aspirin in the presence and absence of inflammatory
      cytokines. Chemerin expression was upregulated by pro-inflammatory stimuli in
      adipocytes but not in hepatocytes. Treatment of stimulated hepatocytes and
      adipocytes with aspirin did not affect chemerin expression. However, treatment of
      inflammatory M1 macrophages with aspirin reduced secretion of the pro
      inflammatory cytokines IL-1beta and IL-6, and increased secretion of the anti
      inflammatory IL-10. In summary, we show that plasma chemerin levels are
      associated with markers of inflammation and that they are significantly higher in
      CAD patients not treated with low dose aspirin. In addition, we show that low
      dose aspirin treatment reduces pro-inflammatory cytokine secretion by
      macrophages, which may lead to reduced chemerin secretion by adipocytes and may
      be a reason for the lower chemerin levels in the circulation of CAD patients on
      low dose aspirin. 

PMID- 24880898
TI  - High antibody titres against predicted Mycoplasma surface proteins do not prevent
      sequestration in infected lung tissue in the course of experimental contagious
      bovine pleuropneumonia.
AB  - Contagious bovine pleuropneumonia (CBPP), a severe respiratory disease of cattle
      caused by Mycoplasma mycoides subsp. mycoides (Mmm) is endemic in many African
      countries due to fragmented veterinary services and the lack of an efficient
      vaccine and sensitive diagnostics. More efficient tools to control the disease
      are needed, but to develop the tools, a better understanding of host-pathogen
      interactions is necessary. The aim of this study was to characterize the kinetics
      of the humoral immune response against 65 Mmm surface antigens for an extended
      period in cattle that survived a primary infection with Mmm. We describe clinical
      and haematological outcomes, and dissect the humoral immune response over time,
      to specific antigens and compared the antibody responses between different
      pathomorphological outcomes. No antigen-specific antibodies correlating with
      protection were identified. Interestingly we found that animals that developed
      Mycoplasma-containing sequestra had significantly higher antibody levels against
      proteins comprising the surface proteome than the animals that cleared Mycoplasma
      from their lungs. Based on these data we suggest that high antibody titres might
      play a role in the establishment of pathomorphological changes, such as
      vasculitis, which should be investigated in future studies. Beneficial antibody
      specificities and cellular immune responses need to be identified in order to
      foster the development of an improved vaccine in the future. 

PMID- 24880899
TI  - Denoising NMR time-domain signal by singular-value decomposition accelerated by
      graphics processing units.
AB  - We present a post-processing method that decreases the NMR spectrum noise without
      line shape distortion. As a result the signal-to-noise (S/N) ratio of a spectrum
      increases. This method is called Cadzow enhancement procedure that is based on
      the singular-value decomposition of time-domain signal. We also provide software
      whose execution duration is a few seconds for typical data when it is executed in
      modern graphic-processing unit. We tested this procedure not only on low
      sensitive nucleus (29)Si in hybrid materials but also on low gyromagnetic ratio,
      quadrupole nucleus (87)Sr in reference sample Sr(NO3)2. Improving the spectrum
      S/N ratio facilitates the determination of T/Q ratio of hybrid materials. It is
      also applicable to simulated spectrum, resulting shorter simulation duration for
      powder averaging. An estimation of the number of singular values needed for
      denoising is also provided. 

PMID- 24880901
TI  - Groundwater resources management through the applications of simulation modeling:
      a review.
AB  - The global population is increasing rapidly and expected to touch the 9.5 billion
      mark by 2050 from the current 7.2 billion. The management of the groundwater
      resources is a challenging task worldwide against the backdrop of the growing
      water demand for industrial, agricultural, and domestic uses and shrinking
      resources. Moreover, this task has been hampered significantly due to
      declining/rising groundwater levels and associated contamination. A broad range
      of solutions could be considered to address the aforementioned problems of
      groundwater management, but the effectiveness of all the solutions and their
      combinations cannot be verified with field experiments. Given their predictive
      capability, simulation models are often the only viable means of providing input
      to management decisions, as they can forecast the likely impacts of a particular
      water management strategy. This paper presents a comprehensive review on the
      simulation modeling applications for the management of groundwater resources. The
      past papers on the overview of groundwater simulation models, use of remote
      sensing and GIS in groundwater modeling, and application of simulation models in
      arid and semiarid regions are described in detail. Conclusions are drawn where
      gaps exist and more research needs to be focused. 

PMID- 24880900
TI  - Measuring success: results from a national survey of recruitment and retention
      initiatives in the nursing workforce.
AB  - OBJECTIVES: The purpose of this study was to identify common components of
      diversity pipeline programs across a national sample of nursing institutions and
      determine what effect these programs have on increasing underrepresented minority
      enrollment and graduation. DESIGN: Linked data from an electronic survey
      conducted November 2012 to March 2013 and American Association of Colleges of
      Nursing baccalaureate graduation and enrollment data (2008 and 2012).
      PARTICIPANTS: Academic and administrative staff of 164 nursing schools in 26
      states, including Puerto Rico in the United States. METHODS: Chi-square
      statistics were used to (1) describe organizational features of nursing diversity
      pipeline programs and (2) determine significant trends in underrepresented
      minorities' graduation and enrollment between nursing schools with and without
      diversity pipeline programs RESULTS: Twenty percent (n = 33) of surveyed nursing
      schools reported a structured diversity pipeline program. The most frequent
      program measures associated with pipeline programs included mentorship, academic,
      and psychosocial support. Asian, Hispanic, and Native Hawaiian/Pacific Islander
      nursing student enrollment increased between 2008 and 2012. Hispanic/Latino
      graduation rates increased (7.9%-10.4%, p = .001), but they decreased among Black
      (6.8%-5.0%, p = .004) and Native American/Pacific Islander students (2.1 %-0.3%,
      p >= .001). CONCLUSIONS: Nursing diversity pipeline programs are associated with
      increases in nursing school enrollment and graduation for some, although not all,
      minority students. Future initiatives should build on current trends while
      creating targeted strategies to reverse downward graduation trends among Black,
      Native American, and Pacific Island nursing students.

PMID- 24880902
TI  - Structure-activity relationship and interaction studies of new SIRT1 inhibitors
      with the scaffold of 3-(furan-2-yl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole.
AB  - SIRT1 is a NAD(+)-dependent deacetylase. It deacetylates a broad range of
      substrates and is involved in multiple diseases such as type 2 diabetes and
      cancer. Here we discovered a new class of SIRT1 inhibitors with the scaffold of 3
      (furan-2-yl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole. The inhibitors up-regulate
      acetyl p53 level in human breast cells MCF-7. The docking simulations indicated
      that the scaffold and the R-substituents of the inhibitors bind in the C and D
      pocket of SIRT1, respectively, which was supported by the structure-activity
      relationship and SIRT1 mutagenesis studies. We propose that binding of the
      inhibitors repels the entering of the nicotinamide moiety of NAD(+) to the C
      pocket, prevents its transformation to the productive conformation and therefore
      inhibits the deacetylation catalyzed by SIRT1. 

PMID- 24880903
TI  - Discovery of a series of aryl-N-(3-(alkylamino)-5
      (trifluoromethyl)phenyl)benzamides as TRPA1 antagonists.
AB  - We describe the discovery and advancement of a novel series of TRPA1 antagonist
      having an aryl-N-(3-(alkylamino)-5-(trifluoromethyl)phenyl)benzamide scaffold.
      The physical and in vitro DMPK profiles are discussed. 

PMID- 24880904
TI  - Vitreopapillary traction in eyes with idiopathic epiretinal membrane: a spectral
      domain optical coherence tomography study.
AB  - PURPOSE: To investigate the prevalence of vitreopapillary traction (VPT) and its
      effect on peripapillary structure and visual function in eyes with idiopathic
      epiretinal membrane (ERM). DESIGN: Observational, comparative study.
      PARTICIPANTS: Patients with idiopathic ERM (n = 116 eyes) and controls with
      similar age (n = 62 eyes). METHODS: Spectral domain optical coherence tomography
      (SD-OCT) axial optic disc scans were evaluated to identify VPT in eyes with
      idiopathic ERM. Based on VPT presence/absence, eyes were categorized as ERM with
      VPT (ERM+VPT, n = 52 eyes) or ERM without VPT (ERM-VPT, n = 64 eyes). Optic nerve
      head (ONH) parameters, average and sectoral retinal nerve fiber layer (RNFL)
      thickness, and central macular thickness (CMT) were compared between groups. Best
      corrected visual acuity (BCVA) and visual field (VF) (automated Humphrey central
      30-2 perimetry) mean deviation (MD) and pattern standard deviation (PSD) were
      compared between groups. MAIN OUTCOME MEASURES: The ONH parameters, peripapillary
      RNFL thickness, BCVA, VF MD, and PSD. RESULTS: Fifty-two of 116 eyes (44.8%) with
      idiopathic ERM had VPT. The ERM+VPT group had larger rim area, smaller average
      and vertical cup-to-disc ratios, and smaller cup volume than ERM-VPT and normal
      groups (all P < 0.001). Eyes with VPT had greater CMT than eyes without VPT
      (421.87+/-97.31 MUm vs. 377.08+/-75.1 MUm; P = 0.006). Average and temporal RNFL
      thickness was higher in ERM+VPT (98.64+/-9.33 MUm and 93.90+/-23.42 MUm) than in
      normal eyes (94.02+/-8.45 MUm and 66.42+/-12.71 MUm). No significant difference
      in BCVA was found between ERM-VPT and ERM+VPT eyes, but MD was lower in ERM+VPT
      than in ERM-VPT (-3.91+/-3.68 dB vs. -2.18+/-2.42 dB; P = 0.005). Additionally,
      PSD was greater in ERM+VPT. Multivariate logistic regression analysis revealed
      that age (odds ratio [OR], 1.190; P = 0.014) and increased CMT (OR, 1.013; P =
      0.005) were associated with vision loss, whereas VPT presence was associated with
      VF defects (OR, 6.290; P = 0.024). CONCLUSIONS: Vitreopapillary traction was
      observed in >40% of eyes with idiopathic ERM, as confirmed by SD-OCT imaging.
      Vitreopapillary traction with idiopathic ERM was associated with altered optic
      disc architecture, increased average and temporal RNFL thickness, and VF defects.

PMID- 24880905
TI  - In vitro evaluations of topical agents to treat Acanthamoeba keratitis.
AB  - PURPOSE: To evaluate the effectiveness of topical agents for the treatment of
      Acanthamoeba keratitis (AK). DESIGN: Laboratory research. PARTICIPANTS: Fifty-six
      Acanthamoeba isolates from 56 patients with clinically proven AK were studied.
      METHODS: The effectiveness of 7 agents against Acanthamoeba cysts was determined
      in vitro. The agents were 1.0% povidone-iodine, 0.05% benzalkonium chloride
      (BZC), 0.02% chlorhexidine gluconate (CHG), 0.1% propamidine isethionate, 0.02%
      polyhexamethylene biguanide (PHMB), 5.0% natamycin, and 1.0% voriconazole (VRCZ).
      These concentrations are those recommended for patients. In addition, 10-fold
      dilutions of each of the agents were tested. After exposing the cysts to each
      agent at 35 degrees C for 1 hour or 24 hours, the agents were removed by
      centrifugal washing. The exposed cysts were observed by optical microscopy for 7
      days. In addition, the fine structures of the exposed isolates were examined by
      transmission electron microscopy (TEM). The genotype of the isolates was
      determined by 18S rDNA fragment sequencing. MAIN OUTCOME MEASURES: The in vitro
      susceptibility was determined by complete growth inhibition, and the morphologic
      appearance was determined by TEM. The genotypes of the 56 isolates were
      determined by 18S rDNA fragment sequencing. RESULTS: The Acanthamoeba cysts were
      most susceptible to natamycin, followed by povidone-iodine, BZC, PHMB,
      propamidine, and CHG. None of the strains was susceptible to VRCZ. The
      susceptibilities to PHMB and CHG may be time dependent and to propamidine may be
      concentration dependent. Transmission electron microscopy showed changes in the
      inner structure of the cysts exposed to natamycin and povidone-iodine. The
      Acanthamoeba genotype was T4 in 52 isolates, and cysts with the same genotype had
      different agent susceptibilities. CONCLUSIONS: Natamycin and povidone-iodine had
      excellent cysti-static (or cystcidal) effects, and PHMB and propamidine did not.
      There was no correlation between agent effectiveness and Acanthamoeba genotype.
      Therefore, susceptibility tests of isolates are needed to choose the most
      appropriate agent, and our results can be a guideline for choosing the most
      appropriate agent for immediate empirical treatment of AK.

PMID- 24880907
TI  - The effects of the administration of oral nutritional supplementation with
      medication rounds on the achievement of nutritional goals: a randomized
      controlled trial.
AB  - BACKGROUND & AIMS: Oral nutritional supplements (ONS) are often considered for
      hospitalized patients with acute severe malnutrition, however the compliance to
      the supplements is known to be variable. The aim of our study was to investigate
      whether providing a lower volume of ONS at a higher frequency during medication
      rounds would improve the intake of the supplements. METHODS: In this randomized
      controlled trial, 234 malnourished inpatients (mean age 71.2 years, 55% male,
      median LOS 10 days) were randomized to receive ONS (300 kcal and 12 g Protein per
      125 ml serving) in one of three different schemes. The usual care group (n = 88)
      was offered ONS 125 ml twice per day in between meals. This was compared to two
      intervention groups that were offered ONS during medication rounds: intervention
      group 1 (n = 66) received 125 ml of ONS twice per day, at 12 and 17 o'clock, and
      intervention group 2 (n = 80) received 62 ml of ONS four times a day, at 8, 12,
      17 and 20 o'clock. Follow-up was performed until discharge or until ONS was no
      longer needed, with a maximum follow-up period of 30 days. The primary outcome
      measure was the percentage of patients who consumed at least 75% of the
      prescribed volume of ONS. RESULTS: No significant differences were observed
      between the control groups and intervention group 1 (risk difference of -16.0%
      (95% CI -33.2-1.2). However, the percentage of patients consuming at least 75% of
      the prescribed ONS was higher in intervention group 2, with a risk difference
      23.4% (95% CI 7.8-39.0%) and a mean increased intake of 35 ml (84 kcal) per day,
      p < 0.001). Median time ONS were taken was 5 days (range 1-17). CONCLUSION: A
      higher frequency of a lower volume of ONS during medication rounds increased the
      compliance of patients needing ONS. Clinical trial registration number NTR2535;
      www.trialregister.nl.

PMID- 24880906
TI  - Imaging of nuclear factor kappaB activation induced by ionizing radiation in
      human embryonic kidney (HEK) cells.
AB  - Ionizing radiation modulates several signaling pathways resulting in
      transcription factor activation. Nuclear factor kappa B (NF-kappaB) is one of the
      most important transcription factors that respond to changes in the environment
      of a mammalian cell. NF-kappaB plays a key role not only in inflammation and
      immune regulation but also in cellular radiation response. In response to DNA
      damage, NF-kappaB might inhibit apoptosis and promote carcinogenesis. Our
      previous studies showed that ionizing radiation is very effective in inducing
      biological damages. Therefore, it is important to understand the radiation
      induced NF-kappaB signaling cascade. The current study aims to improve existing
      mammalian cell-based reporter assays for NF-kappaB activation by the use of DD
      tdTomato which is a destabilized variant of red fluorescent protein tdTomato. It
      is demonstrated that exposure of recombinant human embryonic kidney cells
      (HEK/293 transfected with a reporter constructs containing NF-kappaB binding
      sites in its promoter) to ionizing radiation induces NF-kappaB-dependent DD
      tdTomato expression. Using this reporter assays, NF-kappaB signaling in mammalian
      cells was monitored by flow cytometry and fluorescence microscopy. Activation of
      NF-kappaB by the canonical pathway was found to be quicker than by the genotoxin-
      and stress-induced pathway. X-rays activate NF-kappaB in HEK cells in a dose
      dependent manner, and the extent of NF-kappaB activation is higher as compared to
      camptothecin. 

PMID- 24880908
TI  - Overexpression of Arabidopsis MYB96 confers drought resistance in Camelina sativa
      via cuticular wax accumulation.
AB  - KEY MESSAGE: Camelina has been highlighted as an emerging oilseed crop.
      Transgenic Camelina plants overexpressing Arabidopsis MYB96 exhibited drought
      resistance by activating expression of Camelina wax biosynthetic genes and
      accumulating wax load. Camelina (Camelina sativa L.) is an oilseed crop in the
      Brassicaeae family with potential to expand biofuel production to marginal land.
      The aerial portion of all land plants is covered with cuticular wax to protect
      them from desiccation. In this study, the Arabidopsis MYB96 gene was
      overexpressed in Camelina under the control of the CaMV35S promoter. Transgenic
      Camelina plants overexpressing Arabidopsis MYB96 exhibited normal growth and
      development and enhanced tolerance to drought. Deposition of epicuticular wax
      crystals and total wax loads increased significantly on the surfaces of
      transgenic leaves compared with that of non-transgenic plants. The levels of
      alkanes and primary alcohols prominently increased in transgenic Camelina plants
      relative to non-transgenic plants. Cuticular transpiration occurred more slowly
      in transgenic leaves than that in non-transgenic plants. Genome-wide
      identification of Camelina wax biosynthetic genes enabled us to determine that
      the expression levels of CsKCS2, CsKCS6, CsKCR1-1, CsKCR1-2, CsECR, and CsMAH1
      were approximately two to sevenfold higher in transgenic Camelina leaves than
      those in non-transgenic leaves. These results indicate that MYB96-mediated
      transcriptional regulation of wax biosynthetic genes is an approach applicable to
      generating drought-resistant transgenic crops. Transgenic Camelina plants with
      enhanced drought tolerance could be cultivated on marginal land to produce
      renewable biofuels and biomaterials.

PMID- 24880910
TI  - A novel two-stage approach for epistasis detection in genome-wide case-control
      studies.
AB  - A significant challenge in epistasis detection is the huge amount of data, which
      leads to combinatorial explosion. This study focuses on a two-stage approach for
      detecting epistasis only among single nucleotide polymorphisms (SNPs) that show
      some marginal effect. We present this two-stage approach based on the fusion of
      two criteria (TwoFC) to detect epistatic interactions. We fuse the G (2) test and
      absolute probability difference function as a scoring function to measure the
      strength of association between SNPs and disease status. The fused scoring
      function is an excellent measure of the strength of such an association. The two
      stage strategy greatly reduces the computation load on epistasis detection. We
      use both simulated data sets and a real disease data set to evaluate our method.
      The results of an experiment on the simulated data sets show that TwoFC exhibits
      high power and sample efficiency. The results of an experiment on the real
      disease data set show that our method performs well even with large-scale data
      sets.

PMID- 24880911
TI  - Varicella zoster exposure in IBD patients: rethink the rash decision.

PMID- 24880912
TI  - Single antiplatelet therapy after percutaneous coronary intervention in patients
      allergic to aspirin.
AB  - Dual antiplatelet therapy including aspirin and a P2Y12 ADP receptor antagonist
      is given after percutaneous coronary intervention to avoid catastrophic
      complication of stent thrombosis. Dual antiplatelet therapy is associated with
      increased bleeding risk and may not be tolerated by many patients. This article
      presents the patients, which had to be given single antiplatelet therapy after
      percutaneous coronary intervention and discusses the possible factors responsible
      for the success of single antiplatelet therapy strategy in these patients, in the
      current era of newer antiplatelet agents and coronary stents. 

PMID- 24880913
TI  - Peri-stent contrast staining, major evaginations and severe malapposition after
      biolimus-eluting stent implantation: a case report based on coronary optical
      frequency domain imaging.
AB  - Peri-stent contrast staining and late acquired malapposition represent
      pathological vessel wall healing patterns following percutaneous coronary
      intervention with stent implantation. Earlier studies have described these
      abnormal vessel wall responses commonly present after implantation of first
      generation drug-eluting stents. These coronary vascular changes can cause flow
      disturbance and thereby dispose for later thrombotic events. This case report,
      based on coronary optical frequency domain imaging, describes peri-stent contrast
      staining, major evaginations and severe malapposition occurring 18months after
      third-generation biolimus-eluting stent implantation. 

PMID- 24880914
TI  - Synthesis and preliminary evaluation of novel (99m)Tc-labeled folate derivative
      via click reaction for SPECT imaging.
AB  - The folate receptor is over expressed in a wide variety of human tumors. In this
      study, a novel (99m)Tc-labeled folate derivative ((99m)Tc-HYNIC-T-FA) was
      synthesized as a potential FR-targeting imaging probe and its efficiency was
      evaluated. This (99m)Tc-complex could be obtained through practical manner and
      showed improved in vivo characteristics compared with other radiofolates. Thus,
      this novel (99m)Tc-HYNIC-T-FA compound could serve as a potential imaging agent
      for folate receptor positive tumors. 

PMID- 24880915
TI  - Cross sections of deuteron induced reactions on (nat)Sm for production of the
      therapeutic radionuclide 145Sm and 153Sm.
AB  - At present, targeted radiotherapy (TR) is acknowledged to have great potential in
      oncology. A large list of interesting radionuclides is identified, including
      several radioisotopes of lanthanides, amongst them (145)Sm and (153)Sm. In this
      work the possibility of their production at a cyclotron was investigated using a
      deuteron beam and a samarium target. The excitation functions of the
      (nat)Sm(d,x)(145,153)Sm reactions were determined for deuteron energies up to 50
      MeV using the stacked-foil technique and high-resolution gamma-ray spectrometry.
      The measured cross sections and the contributing reactions were analyzed by
      comparison with results of the ALICE, EMPIRE and TALYS nuclear reaction codes. A
      short overview and comparison of possible production routes is given.

PMID- 24880909
TI  - Regulation of autophagy by amino acids and MTOR-dependent signal transduction.
AB  - Amino acids not only participate in intermediary metabolism but also stimulate
      insulin-mechanistic target of rapamycin (MTOR)-mediated signal transduction which
      controls the major metabolic pathways. Among these is the pathway of autophagy
      which takes care of the degradation of long-lived proteins and of the elimination
      of damaged or functionally redundant organelles. Proper functioning of this
      process is essential for cell survival. Dysregulation of autophagy has been
      implicated in the etiology of several pathologies. The history of the studies on
      the interrelationship between amino acids, MTOR signaling and autophagy is the
      subject of this review. The mechanisms responsible for the stimulation of MTOR
      mediated signaling, and the inhibition of autophagy, by amino acids have been
      studied intensively in the past but are still not completely clarified. Recent
      developments in this field are discussed. 

PMID- 24880917
TI  - Changes in muscle activation following balance and technique training and a
      season of Australian football.
AB  - OBJECTIVES: Determine if balance and technique training implemented adjunct to
      1001 male Australian football players' training influenced the
      activation/strength of the muscles crossing the knee during pre-planned and
      unplanned sidestepping. DESIGN: Randomized Control Trial. METHODS: Each
      Australian football player participated in either 28 weeks of balance and
      technique training or 'sham' training. Twenty-eight Australian football players
      (balance and technique training, n=12; 'sham' training, n=16) completed
      biomechanical testing pre-to-post training. Peak knee moments and directed co
      contraction ratios in three degrees of freedom, as well as total muscle
      activation were calculated during pre-planned and unplanned sidestepping.
      RESULTS: No significant differences in muscle activation/strength were observed
      between the 'sham' training and balance and technique training groups. Following
      a season of Australian football, knee extensor (p=0.023) and semimembranosus
      (p=0.006) muscle activation increased during both pre-planned sidestepping and
      unplanned sidestepping. Following a season of Australian football, total muscle
      activation was 30% lower and peak valgus knee moments 80% greater (p=0.022)
      during unplanned sidestepping when compared with pre-planned sidestepping.
      CONCLUSIONS: When implemented in a community level training environment, balance
      and technique training was not effective in changing the activation of the
      muscles crossing the knee during sidestepping. Following a season of Australian
      football, players are better able to support both frontal and sagittal plane knee
      moments. When compared to pre-planned sidestepping, Australian football players
      may be at increased risk of anterior cruciate ligament injury during unplanned
      sidestepping in the latter half of an Australian football season.

PMID- 24880916
TI  - Genetic characterization of an H5N1 avian influenza virus from a vaccinated duck
      flock in Vietnam.
AB  - This study reports the genetic characterization of a highly pathogenic avian
      influenza virus subtype H5N1 isolated from a moribund domestic duck in central
      Vietnam during 2012. In the moribund duck's flock, within 6 days after
      vaccination with a commercial H5N1 vaccine (Re-5) to 59-day-old birds, 120 out of
      2,000 ducks died. Genetic analysis revealed a substantial number of mutations in
      the HA gene of the isolate in comparison with the vaccine strains, Re-1 and Re-5.
      Similar mutations were also found in selected Vietnamese H5N1 strains isolated
      since 2009. Mutations in the HA gene involved positions at antigenic sites
      associated with antibody binding and also neutralizing epitopes, with some of the
      mutations resulting in the modification of N-linked glycosylation of the HA.
      Those mutations may be related to the escape of virus from antibody binding and
      the infection of poultry, interpretations which may be confirmed through a
      reverse genetics approach. The virus also carried an amino acid substitution in
      the M2, which conferred a reduced susceptibility to amantadine, but no
      neuraminidase inhibitor resistance markers were found in the viral NA gene.
      Additional information including vaccination history in the farm and the
      surrounding area is needed to fully understand the background of this outbreak.
      Such understanding and expanded monitoring of the H5N1 influenza viruses
      circulating in Vietnam is an urgent need to provide updated information to
      improve effective vaccine strain selection and vaccination protocols, aiding
      disease control, and biosecurity to prevent H5N1 infection in both poultry and
      humans. 

PMID- 24880918
TI  - Response to letter to the editor.

PMID- 24880920
TI  - Overview of the US FDA medical device approval process.
AB  - Increasing barriers to medical device innovation in the United States including
      constrained financial resources and rising research costs require that physicians
      take on greater involvement in medical device development, evaluation, and
      regulatory processes. Such involvement requires that physicians understand basic
      aspects of the regulatory process for medical devices and recognize the myriad
      opportunities for involvement in these activities. 

PMID- 24880919
TI  - Interval between neoadjuvant treatment and definitive surgery in locally advanced
      rectal cancer: impact on response and oncologic outcomes.
AB  - PURPOSE: The optimal waiting period between neoadjuvant treatment completion and
      surgery in locally advanced rectal cancer (LARC) is controversial. The specific
      purpose of this study was to evaluate the effect of prolonging this interval on
      the pathologic response, postoperative morbidity, and long-term oncologic
      outcomes. METHODS: Retrospective data analysis is reported from LARC patients who
      had been treated with chemoradiation followed by surgery and intra-operative
      radiotherapy, between February 1995 and December 2012. In total, two groups were
      studied, according to the time elapsed between neoadjuvant treatment and surgery:
      conventional interval (CI; <6 weeks) and delayed interval (DI; >=6 weeks).
      Clinicopathological data related to tumor response, postoperative morbidity, and
      oncologic outcomes were compared. RESULTS: This study included 335 consecutive
      LARC patients. There was a higher proportion of patients with clinical staging
      nodal involvement (cN+) in the DI group (76.6 vs. 64.1 %; p = 0.01). The
      pathologic complete response (pCR) was not significantly different among groups
      (8.8 vs. 12.1 %; p = 0.34). Longer intervals did not affect complication
      incidence or severity or hospital admission length. Certain postneoadjuvant tumor
      effect parameters were significantly increased in the DI group, including N
      downstaging and T-downsizing. After a median follow-up of 71 months, patients in
      the DI group presented with superior 5-year overall survival (OS) (55.9 vs. 70.4
      %, p = 0.014); however, no statistically significant differences were observed in
      5-year disease-free survival (DFS) or 5-year local control (LC) (69.9 vs. 74.9 %,
      p = 0.223; 90.4 vs. 94.5 %, p = 0.123, respectively). CONCLUSIONS: A modest
      surgical interval delay (>=6 weeks) did not increase postoperative complications
      and was identified as a favorable prognostic factor for OS, although no
      differences were observed in pCR, LC, or DFS. Innovative multidisciplinary
      strategies incorporating further time extension of the surgical interval can be
      safely explored.

PMID- 24880921
TI  - Biobanks and their importance in the clinical and scientific fields related to
      Spanish biomedical research.
AB  - The reality of biomedical research in Spain requires having an updated knowledge
      of the research reality and its ethical/legal framework. Research studies with
      human biological samples should be made with a sufficiently large number of
      samples to reflect the diversity of the human population, which meets the
      standard requirements to ensure optimum quality of the research results for
      further development. Furthermore, research with humans, and obtaining and/or
      deriving human biological samples and clinical research studies information is
      subject to a number of legal requirements and restrictions. Biobanks and biobank
      networks are established as the optimal structures that favor the storage of
      large volumes of human biological samples based on criteria to ensure their
      optimum quality, harmonization and security, respecting at all times, the ethical
      and legal requirements guaranteeing the rights of citizens. 

PMID- 24880922
TI  - Protective effects of caffeic acid phenethyl ester (CAPE) against neomycin
      induced hair cell damage in zebrafish.
AB  - OBJECTIVE: Caffeic acid phenethyl ester (CAPE) is known to reduce the generation
      of oxygen-derived free radicals, which is a major mechanism of aminoglycoside
      induced ototoxicity. The objective of the present study was to evaluate the
      effects of CAPE on neomycin-induced ototoxicity in zebrafish (Brn3c: EGFP).
      METHODS: Five-day post-fertilization zebrafish larvae (n=10) were exposed to 125
      MUM neomycin and one of the following CAPE concentrations for 1h: 50, 100, 250,
      500, or 1000 MUM. Ultrastructural changes were evaluated using scanning electron
      microscopy (SEM). The terminal deoxynucleotidyl transferase (TdT)-mediated dUTP
      biotin nick-end labeling (TUNEL) assay and 2-[4-(dimethylamino)styryl]-N
      ethylpyridiniumiodide (DASPEI) assay were performed for evaluation of apoptosis
      and mitochondrial damage. RESULTS: CAPE decreased neomycin-induced hair cell loss
      in the neuromasts (500 MUM CAPE: 12.7 +/- 1.1 cells, 125 MUM neomycin only: 6.3
      +/- 1.1 cells; n = 10, P < 0.05). In the ultrastructural analysis, structures of
      mitochondria and hair cells were preserved when exposed to 125 MUM neomycin and
      500 MUM CAPE. CAPE decreased apoptosis and mitochondrial damage. CONCLUSION: In
      the present study, CAPE attenuated neomycin-induced hair cell damage in
      zebrafish. The results of the current study suggest that neomycin induces
      apoptosis, and the apoptotic cell death can be prevented by treatment with CAPE
      in zebrafish.

PMID- 24880923
TI  - Relationship between obstructive sleep apnea-specific symptoms and cardiac
      function before and after adenotonsillectomy in children with adenotonsillar
      hypertrophy.
AB  - OBJECTIVE: The aim of our study was to investigate subclinical cardiac
      disturbances in patients with symptoms due to adenotonsillar hypertrophy (ATH)
      and the impact of adenotonsillectomy (AT) using conventional and novel
      echocardiographic measures. MATERIAL AND METHODS: Thirty patients with grade 3 or
      4 ATH (mean age: 7.86 +/- 3.83 years; 10 females) and 30 healthy, age- and sex
      matched volunteers (mean age, 8 +/- 2.77; 14 females) were enrolled in the study.
      In addition to conventional two-dimensional and Doppler echocardiographic
      parameters, tissue Doppler parameters, including myocardial performance indices
      (MPIs) of both the right (RV) and left ventricle (LV), were studied. The severity
      of obstructive sleep apnea (OSA) was determined using the OSA-18 health quality
      questionnaire. The OSA-18 questionnaire and echocardiographic examination were
      repeated after AT in patients with ATH. RESULTS: The total OSA-18 scores for the
      control, preoperative, and postoperative groups were 39.56 +/- 19.98, 80.63 +/-
      22.32, and 44.10 +/- 20.31, respectively. Conventional parameters were not
      different among the groups. The mean pulmonary artery pressure estimated using
      the Mahan formula was increased in the ATH group compared with that in the
      control group (21.72 +/- 4.25 vs. 12.43 +/- 3.83, respectively; p<0.001) and
      significantly improved after AT (21.72 +/- 4.25 vs. 16.09 +/- 4.53; p<0.001). The
      RV MPI was significantly different between the control and ATH groups (0.322 +/-
      0.052 vs. 0.383 +/- 0.079, respectively; p=0.001). Both the LV and RV MPI
      significantly improved (0.515 +/- 0.066 vs. 0.434 +/- 0.052, p<0.001; and 0.383
      +/- 0.079 vs. 0.316 +/- 0.058, p=0.018, respectively) after surgery for ATH.
      CONCLUSIONS: Our study revealed that the patients with OSA-specific symptoms due
      to ATH had higher pulmonary artery pressure and impaired RV function according to
      novel echocardiographic parameters. Surgery for ATH seems to have an important
      effect on both LV and RV function.

PMID- 24880924
TI  - Vestibular function in children with auditory neuropathy spectrum disorder.
AB  - OBJECTIVE: Children with auditory neuropathy spectrum disorder (ANSD) account for
      about 10% of paediatric patients referred for cochlear implantation.
      Vestibulopathy may be associated with ANSD, and may have implications when
      formulating management plans in this patient group. We wanted to determine the
      incidence and predictive factors for vestibulopathy in this patient group to
      guide vestibular testing in this patient population, and give insight to the
      aetiology of ANSD. METHODS: We reviewed the outcomes of vestibular function
      testing in a cohort of paediatric patients with ANSD. RESULTS: Probable or
      definite vestibulopathy was seen in 42% of patients who were tested.
      Vestibulopathy was associated with medical co-morbidities, but was not associated
      with imaging findings. CONCLUSIONS: Vestibulopathy is relatively prevalent in
      this patient group, and should be considered when planning the investigation and
      management of children with ANSD.

PMID- 24880925
TI  - Does septoplasty improve the quality of life in children?
AB  - OBJECTIVES: The aim of this study is to evaluate the outcomes of septoplasty and
      the effects of septoplasty on the quality of life and to determine postoperative
      patient satisfaction in children using nose obstruction symptom evaluation (NOSE)
      and visual analog scale (VAS). METHODS: Only pediatric patients who underwent
      septoplasty were included in the study. Patients who underwent adenoidectomy,
      endoscopic sinus surgery, or turbinate surgery in addition to septoplasty and
      total septal reconstruction with open technique septorhinoplasty were excluded
      from the study. Patients and their parents were inquired about their nasal
      obstruction symptoms using the NOSE scale before and 3 and 12 months following
      the surgery. VAS was used to analyze overall satisfaction of the patients and
      their parents on the outcomes of surgery, at the last follow-up examination 12
      months after the surgery. RESULTS: Thirty-five patients with a mean age of 13.4
      +/- 2.8 (8-16) were included in the study. There was a very significant
      improvement in NOSE score at 3 months after septoplasty. The mean subjective
      satisfaction score measured with VAS at the 12th month postoperatively was 7.9 +/
      2.1. Improvement in NOSE score was correlated with patient satisfaction.
      CONCLUSION: Septoplasty is a very effective and satisfactory treatment for nasal
      obstruction caused by nasal septal deviation in children. The NOSE scale can be
      used for the evaluation of nasal obstruction symptoms.

PMID- 24880926
TI  - How much does latitude modify temperature-mortality relationship in 13 eastern US
      cities?
AB  - Although several studies have documented that latitude might be an effect
      modifier of the association between temperature and mortality, little is known
      about how much latitude modifies the temperature-mortality relationship. In this
      study, we examined this research question using a distributed lag non-linear
      model and meta-regression analysis based on data from 13 large cities of eastern
      US from the US National Morbidity, Mortality, and Air Pollution Study. We found
      that cold effects lasted about 1 month while hot effects were acute and short
      term. Meta-regression analysis showed that latitude modified both the cold and
      hot effects with statistical significance. The cold effect decreased with the
      latitude increment, with -0.11 % change of mortality effect for 1 degrees 
      increment, while the hot effect increased with the latitude increment, with 0.18
      % change of mortality effect for 1 degrees  increment. This finding indicates the
      importance of latitude on temperature-related mortality risk, which is helpful
      for city to develop localized effective adaptation strategy in the context of
      climate change. 

PMID- 24880928
TI  - Denoising traffic collision data using ensemble empirical mode decomposition
      (EEMD) and its application for constructing continuous risk profile (CRP).
AB  - Filtering out the noise in traffic collision data is essential in reducing false
      positive rates (i.e., requiring safety investigation of sites where it is not
      needed) and can assist government agencies in better allocating limited
      resources. Previous studies have demonstrated that denoising traffic collision
      data is possible when there exists a true known high collision concentration
      location (HCCL) list to calibrate the parameters of a denoising method. However,
      such a list is often not readily available in practice. To this end, the present
      study introduces an innovative approach for denoising traffic collision data
      using the Ensemble Empirical Mode Decomposition (EEMD) method which is widely
      used for analyzing nonlinear and nonstationary data. The present study describes
      how to transform the traffic collision data before the data can be decomposed
      using the EEMD method to obtain set of Intrinsic Mode Functions (IMFs) and
      residue. The attributes of the IMFs were then carefully examined to denoise the
      data and to construct Continuous Risk Profiles (CRPs). The findings from
      comparing the resulting CRP profiles with CRPs in which the noise was filtered
      out with two different empirically calibrated weighted moving window lengths are
      also documented, and the results and recommendations for future research are
      discussed. 

PMID- 24880929
TI  - A study of bicyclist kinematics and injuries based on reconstruction of passenger
      car-bicycle accident in China.
AB  - Like pedestrians, bicyclists are vulnerable road users, representing a population
      with a high risk of fatal and severe injuries in traffic accidents as they are
      unprotected during vehicle collisions. The objective of this study is to
      investigate the kinematics response of bicyclists and the correlation of the
      injury severity with vehicle impact speed. Twenty-four car-bicyclist cases with
      detailed information were selected for accident reconstruction using mathematical
      models, which was implemented in the MADYMO program. The dynamic response of
      bicyclists in the typical impact configuration and the correlation of head impact
      conditions were analyzed and discussed with respect to the head impact speed,
      time of head impact and impact angle of bicyclists to vehicle impact speed.
      Furthermore, the injury distribution of bicyclists and the risk of head injuries
      and fractures of lower limbs were investigated in terms of vehicle impact speed.
      The results indicate that wrap-around distance (WAD), head impact speed, time of
      head impact, head impact angle, and throw-out distance (TOD) of the bicyclists
      have a strong relationship with vehicle impact speed. The vehicle impact speed
      corresponding to a 50% probability of head AIS 2+ injuries, head AIS 3+ injuries,
      and lower limb fracture risk for bicyclists is 53.8km/h, 58.9km/h, and 41.2km/h,
      respectively. A higher vehicle impact speed produces a higher injury risk to
      bicyclist. The results could provide background knowledge for the establishment
      or modification of pedestrian regulations considering bicyclist protection as
      well as being helpful for developing safety measures and protection devices for
      bicyclists. 

PMID- 24880927
TI  - Low-power laser irradiation fails to improve liver regeneration in elderly rats
      at 48 h after 70 % resection.
AB  - The liver regeneration is an important clinical issue after major hepatectomies.
      Unfortunately, many organs (including the liver) exhibit age-related impairments
      regarding their regenerative capacity. Recent studies found that low-power laser
      irradiation (LPLI) has a stimulatory effect on the liver regeneration process.
      However, its effects in elderly remain unknown. Thus, this study aimed to
      investigate the main molecular mechanisms involved in liver regeneration of
      partially hepatectomized elderly rats exposed to LPLI. The effects of 15 min of
      LPLI (wavelength of 632.8 nm; fluence of 0.97 J/cm(2); total energy delivered of
      3.6 J) were evaluated in hepatectomized elderly Wistar male rats. Afterwards,
      through immunoblotting approaches, the protein expression and phosphorylation
      levels of hepatocyte growth factor (HGF), Met, Akt and Erk 1/2 signaling pathways
      as well as the proliferating cell nuclear antigen (PCNA) were investigated. It
      was observed that LPLI was not able to improve liver regeneration in elderly rats
      as evidenced by the lack of improvement of HGF and PCNA protein expression or
      phosphorylation levels of Met, Akt and Erk 1/2 in the remnant livers. In sum,
      this study demonstrated that the main molecular pathway, i.e. HGF/Met -> Akt and
      Erk 1/2 -> PCNA, involved in the hepatic regeneration process was not improved by
      LPLI in elderly hepatectomized rats, which in turn rules out LPLI as an adjuvant
      therapy, as observed in this protocol of liver regeneration evaluation (i.e. at
      48 h after 70 % resection), in elderly.

PMID- 24880930
TI  - Effect of dissolved oxygen on nitrogen and phosphorus removal and electricity
      production in microbial fuel cell.
AB  - Performance of a two-chamber microbial fuel cell (MFC) was evaluated with the
      influence of cathodic dissolved oxygen (DO). The maximum voltage, coulombic
      efficiency and maximum power density outputs of MFC decreased from 521 to 303 mV,
      52.48% to 23.09% and 530 to 178 mW/m(2) with cathodic DO declining. Furthermore,
      a great deal of total phosphorus (TP) was removed owing to chemical precipitation
      (about 80%) and microbial absorption (around 4-17%). COD was first removed in
      anode chamber (>70%) then in cathode chamber (<5%). Most of nitrogen was removed
      when the cathodic DO was at low levels. Chemical precipitates formed in cathode
      chamber were verified as phosphate, carbonate and hydroxyl compound with the aid
      of scanning electron microscope capable of energy dispersive spectroscopy (SEM
      EDS), X-ray diffractometer (XRD) and Fourier transform infrared spectroscopy
      (FTIR).

PMID- 24880931
TI  - Enhancement in hydrogen production by thermophilic anaerobic co-digestion of
      organic fraction of municipal solid waste and sewage sludge--optimization of
      treatment conditions.
AB  - Batch dry-thermophilic anaerobic co-digestion (55 degrees C) of organic fraction
      of municipal solid waste (OFMSW) and sewage sludge (SS) for hydrogen production
      was studied under several sludge combinations (primary sludge, PS; waste
      activated sludge, WAS; and mixed sludge, MS), TS concentrations (10-25%) and
      mixing ratios of OFMSW and SS (1:1, 2.5:1, 5:1, 10:1). The co-digestion of OFMSW
      and SS showed a 70% improvement in hydrogen production rate over the OFMSW
      fermentation only. The co-digestion of OFMSW with MS showed 47% and 115% higher
      hydrogen production potential as compared with OFMSW+PS and OFMSW+WAS,
      respectively. The maximum hydrogen yield of 51 mL H2/g VS consumed was observed
      at TS concentration of 20% and OFMSW to MS mixing ratio of 5:1, respectively. The
      acetic and butyric acids were the main acids in VFAs evolution; however, the
      higher butyric acid evolution indicated that the H2 fermentation was butyrate
      type fermentation.

PMID- 24880932
TI  - Cryptanalysis and improvement of Yan et al.'s biometric-based authentication
      scheme for telecare medicine information systems.
AB  - Remote user authentication is desirable for a Telecare Medicine Information
      System (TMIS) for the safety, security and integrity of transmitted data over the
      public channel. In 2013, Tan presented a biometric based remote user
      authentication scheme and claimed that his scheme is secure. Recently, Yan et al.
      demonstrated some drawbacks in Tan's scheme and proposed an improved scheme to
      erase the drawbacks of Tan's scheme. We analyze Yan et al.'s scheme and identify
      that their scheme is vulnerable to off-line password guessing attack, and does
      not protect anonymity. Moreover, in their scheme, login and password change
      phases are inefficient to identify the correctness of input where inefficiency in
      password change phase can cause denial of service attack. Further, we design an
      improved scheme for TMIS with the aim to eliminate the drawbacks of Yan et al.'s
      scheme. 

PMID- 24880933
TI  - Results of initiatives to address women's issues in cardiovascular health: more
      light than heat?

PMID- 24880934
TI  - Incorporating sex and gender in cardiovascular research: the time has come.

PMID- 24880935
TI  - Myocardium at risk is associated with adverse clinical events in women but not in
      men, after coronary artery bypass grafting.
AB  - BACKGROUND: Women undergoing coronary artery bypass grafting (CABG) are at
      increased risk for morbidity and mortality. Factors responsible for this
      observation include smaller coronary size and delayed presentation. To date, no
      studies have examined the effect of the degree of myocardium at risk (MAR) on the
      relationship between female sex and adverse postoperative events. METHODS:
      Consecutive patients undergoing first-time isolated CABG at a single institution
      from 2002-2007 were identified. MAR was calculated using the weighted Duke Index
      and was categorized as low, moderate, or high. Multivariable logistic regression
      models were created to compare the impact of MAR on adverse clinical events.
      RESULTS: We identified 3741 patients, 3325 (89%) of whom had complete
      angiographic data. Women (n = 755) were older (P = 0.0001) and presented more
      often with hypertension (P = 0.0001), diabetes (P = 0.0001), heart failure (P =
      0.0001), and an urgent/emergent situation (P = 0.002). After surgery, women
      experienced greater rates of adverse events (15.2% vs 9.3%; P = 0.0001). In a
      fully adjusted logistic regression model, the nested interaction of sex in MAR
      showed that women had a significantly greater risk of major adverse
      cardiovascular events (MACE) when MAR was high (odds ratio [OR], 1.9; 95%
      confidence interval [CI], 1.3-2.6; P = 0.0004). Greater severity of MAR emerged
      as an independent predictor of adverse events among women (high: OR, 2.9; 95% CI,
      1.2-7.3; moderate: OR, 2.2; 95% CI, 0.8-5.7; low: OR, 1.0), but not among men.
      CONCLUSIONS: MAR was independently associated with higher rates of adverse events
      among women but not in men undergoing CABG. This finding may help explain
      differences in outcomes seen between women and men after revascularization.

PMID- 24880936
TI  - Apolipoprotein E gene E2/E2 genotype is a genetic risk factor for vertebral
      fractures in humans: a large-scale study.
AB  - PURPOSE: Although many studies have been performed to evaluate whether or not
      apolipoprotein E gene (APOE) polymorphisms are differentially associated with
      bone mineral density (BMD) and fractures, the results have been conflicting. This
      large-scale study was performed to investigate whether a relationship exists
      between APOE polymorphisms and risk of fracture. METHODS: A hospital-based case
      control study was conducted in 3,000 patients with fractures and 3,000 age- and
      gender-matched healthy controls. Polymerase chain reaction restriction fragment
      length polymorphism (PCR-RFLP) assay was applied to assess the APOE gene
      polymorphisms. RESULTS: Patients with fractures had a significantly higher
      frequency of APOE E2/E2 genotype [odds ratio (OR) = 2.02, 95% confidence interval
      (CI) = 1.30, 3.14; P = 0.002] than healthy controls. When stratifying by fracture
      type, it was found that patients with vertebral fractures had a significantly
      higher frequency of APOE E2/E2 genotype (OR = 2.86, 95% CI = 1.73, 4.73; P <
      0.001). No significant differences were found in nonvertebral (hip or wrist or
      other) fractures. CONCLUSIONS: Our study suggests that APOE E2/E2 genotype is a
      potential genetic risk factor for vertebral fractures in humans.

PMID- 24880937
TI  - Mid-term result of ceramic bearings in total hip arthroplasty.
AB  - PURPOSE: The purpose of this study was to evaluate our clinical experience with
      ceramic-on-ceramic cementless total hip arthroplasty (THA) and complications
      after an average follow-up of more than eight years. METHODS: From January 2001
      to December 2008, 540 THA with ceramic-on-ceramic bearings were performed in 448
      patients (92 bilateral, 54 of which were operated simultaneously) with a mean age
      49.9 years (range 18-84) by a senior surgeon. Pre-operative aetiological reasons
      were developmental dysplasia of the hip (DDH) in 205 hips, degenerative arthritis
      in 157 hips, avascular necrosis in 51 hips, rheumatoid diseases in 40 hips,
      posttraumatic arthritis in 40 hips, other reasons in 25 hips and revision surgery
      in 22 hips. Patients were evaluated with Harris hip score (HSS), and radiological
      findings of acetabular and femoral component loosening or osteolysis with ceramic
      bearing related complications like squeaking, liner and head fractures were
      recorded. RESULT: The average duration of follow-up time was 8.2 years (range,
      five to 13.2). The main Harris hip score increased from 42.4 points
      preoperatively to 94.9 points at the time of last follow-up. We had one fracture
      of the ceramic head, 11 clicking and four squeaking; one of them was revised
      because of terrible squeaking due to acetabular liner fracture, the other three
      were seldom audible from the outside and followed conservatively. We did not
      observed loosening or osteolysis due to ceramic bearings at the time of the final
      follow-up. CONCLUSION: Our study has demonstrated that ceramic-on-ceramic
      bearings can be used safely in different etiological problems. Incidences of
      noisy hips are becoming less frequent.

PMID- 24880938
TI  - Immunotherapy in the treatment of non-small cell lung cancer.
AB  - Advances in the understanding of the role of the immune system in tumor
      immunosurveillance have resulted in the recognition that tumors can evade immune
      destruction via the dysregulation of co-inhibitory or checkpoint signals. This
      has led to the development of a generation immunotherapeutic agents targeting the
      immune checkpoint pathway. Recent early phase studies of immune checkpoint
      modulators, such as CTLA-4, PD-1 and PD-L1 inhibitors in NSCLC have reported
      promising results with prolonged clinical responses and tolerable toxicity. This
      article provides an overview of co-stimulatory and inhibitory molecules that
      regulate the immune response to tumors, recent therapies that have been developed
      to exploit these interactions and the role of predictive biomarkers in treatment
      selection. 

PMID- 24880941
TI  - Surgical management of melanoma.
AB  - Surgery remains the mainstay of treatment of every patient in whom complete
      excision of all disease is feasible. For clinically localized melanoma (clinical
      stages 0-II), wide excision and, when appropriate, sentinel lymph node biopsy are
      well established. The management of stage III melanoma is more contentious.
      Resection remains the first choice of therapy for patients with oligometastatic
      melanoma in accessible locations, but careful consideration of preoperative use
      of highly active drugs is appropriate. Decisions regarding surgical management of
      stage IV melanoma should routinely be made in the context of a multidisciplinary
      team approach. 

PMID- 24880939
TI  - State of melanoma: an historic overview of a field in transition.
AB  - The last 30 years has seen a revolution in melanoma. Fundamental elements of the
      surgical, adjuvant medical, and systemic therapy for the disease have been
      significantly altered toward improved management and better outcomes. The intent
      of this article is to reflect on past efforts and research in melanoma and the
      current landscape of treatment of melanoma. The authors also hope to capture the
      excitement currently rippling through the field and the hope for a cure. The
      intent of treatment of advanced melanoma, which was once considered incurable,
      has changed from palliative to potentially curative.

PMID- 24880942
TI  - Melanoma adjuvant therapy.
AB  - Adjuvant therapy targets melanoma micrometastases in patients with surgically
      resected disease that carry a high risk of death from melanoma recurrence. In
      this setting, adjuvant therapy provides the greatest opportunity for cure before
      progression into advanced inoperable stages. In randomized clinical trials,
      interferon-alfa has been shown to have a significant impact on relapse-free
      survival and, at high dosage, on overall survival compared with observation
      (E1684) and the GMK vaccine (E1694). This article reviews melanoma adjuvant
      therapy along with the ongoing and planned clinical trials. 

PMID- 24880940
TI  - Understanding the biology of melanoma and therapeutic implications.
AB  - From 1976 to 2010, only 2 medications were approved for treating metastatic
      melanoma. Between 2011 and 2013, 4 agents were approved and other therapies have
      shown great promise in clinical trials. Fundamental discoveries, such as the
      identification of oncogenic mutations in most melanomas, the elucidation of the
      molecular signaling resulting from these mutations, and the revelation that
      several cell surface molecules serve as regulators of immune activation, have
      been instrumental in this progress. This article summarizes the molecular
      pathogenesis of melanoma, describes the current efforts to target oncogene-driven
      signaling, and presents the rationale for combining immune and molecular
      targeting. 

PMID- 24880943
TI  - Targeted therapies for cutaneous melanoma.
AB  - Melanoma is resistant to cytotoxic therapy, and treatment options for advanced
      disease have been limited historically. However, improved understanding of
      melanoma driver mutations, particularly those involving the mitogen-activated
      protein kinase pathway, has led to the development of targeted therapies that are
      effective in this previously treatment-refractory disease. In cutaneous melanomas
      with BRAF V600 mutations the selective RAF inhibitors, vemurafenib and
      dabrafenib, and the MEK inhibitor, trametinib, have demonstrated survival
      benefits. Early signals of efficacy have also been demonstrated with MEK
      inhibitors in melanomas with NRAS mutations, and KIT inhibitors offer promise in
      melanomas driven through activation of their target receptor. 

PMID- 24880944
TI  - Treatments for noncutaneous melanoma.
AB  - Historically the approach to treating noncutaneous melanoma was largely guided by
      the experience with cutaneous melanoma, particularly in the metastatic setting.
      However, as genetic tools have allowed clinicians to better characterize these
      malignancies, their unique biology has become apparent. The ability to accurately
      distinguish the subtypes of melanoma and the genetic alterations that drive them
      is beginning to yield the tools that are shifting this disease from one that has
      proved to be intractable in the advanced setting to one that can be effectively
      treated. 

PMID- 24880945
TI  - Targeted therapy resistance mechanisms and therapeutic implications in melanoma.
AB  - Although selective mutant BRAF inhibitors have revolutionized the treatment of
      metastatic melanoma, the magnitude and duration of their clinical benefit are
      significantly undermined by de novo and acquired resistance. Functional studies,
      molecular characterization of clinical samples, and clinical trials are providing
      insights into the landscape of resistance mechanisms in this disease. These
      findings have implications for the development of rational therapeutic
      approaches, and have identified several challenges that remain to be overcome if
      outcomes are to be improved in patients with metastatic melanoma. 

PMID- 24880946
TI  - Introduction to the role of the immune system in melanoma.
AB  - The concept of immunosurveillance of cancer has been widely accepted for many
      years, but only recently have the precise mechanisms of tumor-host immune
      interactions been revealed. Inflammatory and immune reactions play a role in
      melanomagenesis, and may contribute to the eradication of tumor as well as
      potentiating its growth and proliferation. Studies of the role of tumor-immune
      system interactions are providing insights into the pathogenesis and
      opportunities for highly effective therapeutic strategies. Some patients, even
      with advanced disease, are now cured with immunotherapy, and increasing numbers
      of such cures are likely in future. 

PMID- 24880947
TI  - Vaccines and melanoma.
AB  - The potential for therapeutic efficacy of a melanoma vaccine has been evident
      preclinically for many years. In melanoma patients, vaccines have resulted in the
      induction of immune responses, although clinical benefit has not been clearly
      documented. The recent achievements with immune-checkpoint blockade have shown
      that immunotherapy can be a powerful tool in cancer therapy. With increased
      understanding of tumor immunity, the limitations of previous cancer vaccination
      approaches have become evident. Rapid progress in technologies that enable better
      vaccine design raise the expectation that these limitations can be overcome, thus
      leading to a clinically effective melanoma vaccine in the near future. 

PMID- 24880948
TI  - Interferon, interleukin-2, and other cytokines.
AB  - Cytokines are a diverse group of signaling molecules with immunomodulatory
      activity. This article reviews the application of cytokine therapy in melanoma
      with a focus on interferon-alpha and interleukin-2. In addition, it addresses the
      clinical considerations of these therapies including patient selection, reduction
      in toxicity, and combination regimens. 

PMID- 24880950
TI  - Combinatorial approach to treatment of melanoma.
AB  - There are multiple effective and well-tolerated systemic therapy treatments for
      the treatment of advanced melanoma, as well as new immunotherapy and targeted
      therapy agents in clinical trials. Traditional cytotoxic chemotherapy and
      targeted BRAF inhibitors can increase antigen presentation and can rebalance the
      intratumoral immune milieu. The combination of pulsed cytotoxic therapy and
      immunotherapy is a logical next step in designing treatment regimens. Combination
      radiotherapy and immunotherapy also has experimental and clinical support. The
      standard of care for patients with advanced melanoma remains participation in
      clinical trials in order to enhance understanding of the effectiveness and
      toxicities of combination regimens. 

PMID- 24880949
TI  - Immune checkpoint blockade.
AB  - Since the development and approval of Ipilimumab, the first immune checkpoint
      inhibitor licensed for the treatment of metastatic melanoma, clinicians have
      gained a better understanding of the mode of action, management of toxicities,
      and assessment of response to this class of drugs. Several antibodies are now in
      development, aimed at blocking novel immune checkpoint molecules, such as PD-1
      and it's corresponding ligand PD-L1. This article summarizes the mechanism of
      action, preclinical development, and subsequent clinical studies of immune
      checkpoint antibodies in melanoma. 

PMID- 24880951
TI  - Hematology/Oncology Clinics of North America. Melanoma. Preface.

PMID- 24880954
TI  - Different impressions of other agents obtained through social interaction
      uniquely modulate dorsal and ventral pathway activities in the social human
      brain.
AB  - Internal (neuronal) representations in the brain are modified by our experiences,
      and this phenomenon is not unique to sensory and motor systems. Here, we show
      that different impressions obtained through social interaction with a variety of
      agents uniquely modulate activity of dorsal and ventral pathways of the brain
      network that mediates human social behavior. We scanned brain activity with
      functional magnetic resonance imaging (fMRI) in 16 healthy volunteers when they
      performed a simple matching-pennies game with a human, human-like android,
      mechanical robot, interactive robot, and a computer. Before playing this game in
      the scanner, participants experienced social interactions with each opponent
      separately and scored their initial impressions using two questionnaires. We
      found that the participants perceived opponents in two mental dimensions: one
      represented "mind-holderness" in which participants attributed anthropomorphic
      impressions to some of the opponents that had mental functions, while the other
      dimension represented "mind-readerness" in which participants characterized
      opponents as intelligent. Interestingly, this "mind-readerness" dimension
      correlated to participants frequently changing their game tactic to prevent
      opponents from envisioning their strategy, and this was corroborated by increased
      entropy during the game. We also found that the two factors separately modulated
      activity in distinct social brain regions. Specifically, mind-holderness
      modulated activity in the dorsal aspect of the temporoparietal junction (TPJ) and
      medial prefrontal and posterior paracingulate cortices, while mind-readerness
      modulated activity in the ventral aspect of TPJ and the temporal pole. These
      results clearly demonstrate that activity in social brain networks is modulated
      through pre-scanning experiences of social interaction with a variety of agents.
      Furthermore, our findings elucidated the existence of two distinct functional
      networks in the social human brain. Social interaction with anthropomorphic or
      intelligent-looking agents may distinctly shape the internal representation of
      our social brain, which may in turn determine how we behave for various agents
      that we encounter in our society. 

PMID- 24880955
TI  - Beger and Frey procedures for treatment of chronic pancreatitis: comparison of
      outcomes at 16-year follow-up.
AB  - BACKGROUND: Chronic pancreatitis is a chronic inflammatory disorder characterized
      by progressive fibrosis of pancreatic tissue. The principal symptom is chronic
      pain resulting in reduced quality of life and inability to work. Short-term
      follow-up has shown that duodenum-preserving pancreatic head resections (DPPHRs)
      are superior in outcomes to pancreaticoduodenectomy. Therefore, these organ
      sparing procedures have gained wide acceptance. This trial was conducted to
      compare patient outcomes 16 years after treatment for chronic pancreatitis by
      means of the Beger or the Frey procedure. STUDY DESIGN: Seventy-four patients
      suffering from chronic pancreatitis were randomly assigned to 2 treatment groups
      (Beger n = 38) and Frey (n = 36). The perioperative courses in the randomized
      controlled trial and the 8-year follow-up have been reported previously. All
      participating patients were contacted with a standardized, validated
      questionnaire to evaluate long-term survival, quality of life, pain, and exocrine
      and endocrine function. RESULTS: No significant differences between the 2 groups
      in terms of quality of life, pain control, or other somatic parameters were
      detected after a median of 16 years postoperatively. Mortality was comparable
      after Beger and Frey procedures at 39% vs 34%, respectively, with postoperative
      survivals of 13.0 +/- 1.1 years and 13.3 +/- 0.9 years, respectively (p = 0.660).
      No statistically significant differences were found in rates of endocrine
      insufficiency (Beger 87% vs Frey 86%; p = 0.953) or exocrine insufficiency (Beger
      77% vs Frey 83%; p = 0.655). CONCLUSIONS: Duodenum-preserving resections of the
      pancreatic head offered good and permanent pain relief and substantially
      increased quality of life in chronic pancreatitis. Overall, a 16-year long-term
      follow-up found comparable outcomes for the Beger and Frey procedures.

PMID- 24880957
TI  - MRI-guided quadrantectomy in patients with ductal carcinoma in situ detected
      preoperatively by mammographic calcifications.
AB  - BACKGROUND: We designed MRI-guided quadrantectomy using 2-dimensional images
      reconstructed from MRI to enable virtual simulation of breast-conserving surgery.
      This study evaluated the efficacy of our approach, which involved projection of
      the 2-dimensional reconstruction images directly onto the breast to guide planned
      resection compared with the conventional approach with preoperative localization
      with hooked wires, for patients with ductal carcinoma in situ (DCIS) detected by
      mammographic calcifications. STUDY DESIGN: Eighty-six patients with
      calcifications >=2 cm in diameter on mammogram who were diagnosed with DCIS on
      preoperative percutaneous biopsy underwent breast-conserving surgery. In 32
      patients, lesion localization was done using the conventional technique of hooked
      wires. In 54 patients, preoperative planning was performed using supine MRI and
      projection of reconstructed 2-dimensional images directly onto the breast
      surface. Surgical outcomes in the 2 groups were compared. In the latter group, we
      also compared accuracy of DCIS detection between supine MRI and specimen
      mammography. RESULTS: Final pathologic assessment of the 86 patients was DCIS in
      67 and DCIS with microinvasion (T1mic) in 19 patients. The rate of additional
      intraoperative margin resection and presence of DCIS at the surgical margin were
      significantly lower with our MRI-guided technique vs the hooked-wire approach.
      Supine MRI detected a considerably larger area of DCIS than did specimen
      mammography. CONCLUSIONS: Compared with a conventional approach using hooked
      wires, our MRI-guided quadrantectomy might be useful for patients with DCIS and
      DCIS with T1mic detected by mammographic calcifications, due to the superior
      ability to detect DCIS on MRI compared with mammography.

PMID- 24880956
TI  - Empowering the surgical patient: a randomized, prospective analysis of an
      innovative strategy for improving patient compliance with preadmission showering
      protocol.
AB  - BACKGROUND: Surgical site infections (SSIs) are responsible for significant
      morbidity, mortality, and excess use of health care resources. The preadmission
      antiseptic shower is accepted as an effective strategy for reducing the risk for
      SSIs. The study analyzes the benefit of an innovative electronic patient alert
      system (EAS) for enhancing compliance with a preadmission showering protocol with
      4% chlorhexidine gluconate (CHG). STUDY DESIGN: After providing informed consent,
      80 volunteers were randomized to 4 CHG showering groups. Groups A1 and A2
      showered twice. Group A1 was prompted to shower via EAS. Groups B1 and B2
      showered 3 times. Group B1 was prompted via EAS. Subjects in groups A2 and B2
      were not prompted (non-EAS groups). Skin-surface concentrations of CHG (MUg/mL)
      were analyzed using colorimetric assay at 5 separate anatomic sites. Study
      personnel were blinded to the randomization code; after final volunteer
      processing, the code was broken and individual groups were analyzed. RESULTS:
      Mean composite CHG skin-surface concentrations were significantly higher (p <
      0.007) in EAS groups A1 (30.9 +/- 8.8 MUg/mL) and B1 (29.0 +/- 8.3 MUg/mL)
      compared with non-EAS groups A2 (10.5 +/- 3.9 MUg/mL) and B2 (9.5 +/- 3.1
      MUg/mL). Overall, 66% and 67% reductions in CHG skin-surface concentrations were
      observed in non-EAS groups A2 and B2 compared with EAS study groups. Analysis of
      returned (unused) CHG (mL) suggests that a wide variation in volume of biocide
      was used per shower in all groups. CONCLUSIONS: The findings suggest that EAS was
      effective in enhancing patient compliance with a preadmission showering protocol,
      resulting in a significant (p < 0.007) increase in skin-surface concentrations of
      CHG compared with non-EAS controls. However, variation in amount of unused 4% CHG
      suggests that rigorous standardization is required to maximize the benefits of
      this patient-centric interventional strategy.

PMID- 24880953
TI  - Graft microvascular disease in solid organ transplantation.
AB  - Alloimmune inflammation damages the microvasculature of solid organ transplants
      during acute rejection. Although immunosuppressive drugs diminish the
      inflammatory response, they do not directly promote vascular repair. Repetitive
      microvascular injury with insufficient regeneration results in prolonged tissue
      hypoxia and fibrotic remodeling. While clinical studies show that a loss of the
      microvascular circulation precedes and may act as an initiating factor for the
      development of chronic rejection, preclinical studies demonstrate that improved
      microvascular perfusion during acute rejection delays and attenuates tissue
      fibrosis. Therefore, preservation of a functional microvasculature may represent
      an effective therapeutic strategy for preventing chronic rejection. Here, we
      review recent advances in our understanding of the role of the microvasculature
      in the long-term survival of transplanted solid organs. We also highlight
      microvessel-centered therapeutic strategies for prolonging the survival of solid
      organ transplants. 

PMID- 24880959
TI  - Assessing carbon and nitrogen removal in a novel anoxic-aerobic cyanobacterial
      bacterial photobioreactor configuration with enhanced biomass sedimentation.
AB  - The carbon and nitrogen removal potential of an innovative anoxic-aerobic
      photobioreactor configuration operated with both internal and external recyclings
      was evaluated under different cyanobacterial-bacterial sludge residence times (9
      31 days) during the treatment of wastewaters with low C/N ratios. Under optimal
      operating conditions, the two-stage photobioreactor was capable of providing
      organic carbon and nitrogen removals over 95% and 90%, respectively. The
      continuous biomass recycling from the settler resulted in the enrichment and
      predominance of rapidly-settling cyanobacterial-bacterial flocs and effluent
      suspended solid concentrations lower than 35 mg VSS L(-1). These flocs exhibited
      sedimentation rates of 0.28-0.42 m h(-1) but sludge volumetric indexes of 333-430
      ml/g. The decoupling between the hydraulic retention time and sludge retention
      time mediated by the external recycling also avoided the washout of nitrifying
      bacteria and supported process operation at biomass concentrations of 1000-1500
      mg VSS L(-1). The addition of additional NaHCO3 to the process overcame the CO2
      limitation resulting from the intense competition for inorganic carbon between
      cyanobacteria and nitrifying bacteria in the photobioreactor, which supported the
      successful implementation of a nitrification-denitrification process.
      Unexpectedly, this nitrification-denitrification process occurred both
      simultaneously in the photobioreactor alone (as a result of the negligible
      dissolved oxygen concentrations) and sequentially in the two-stage anoxic-aerobic
      configuration with internal NO3(-)/NO2(-) recycling.

PMID- 24880958
TI  - Characterization of ciprofloxacin-resistant isolates from a wastewater treatment
      plant and its receiving river.
AB  - In this study we characterised the ciprofloxacin-resistant strains isolated in
      biofilm and sediments from a wastewater treatment plant (WWTP) discharge point
      and its receiving river. We also examined the prevalence of qnrA, qnrB, qnrS and
      aac(6')-Ib-cr genes in these isolates and determined whether they harbour plasmid
      encoded beta-lactamases such as TEM, SHV and CTX-M. Moreover, antibiotic
      concentrations were also measured to evaluate the level of contamination of these
      pharmaceuticals in the sampling area. Antibiotics were found in the range of ng
      L(-1) in WWTP effluents, but most of them were no longer found in downstream
      river. However, some fluoroquinolones were detected in sediment downstream
      demonstrating their high persistence and their capacity to be retained in the
      river sediments. Most of the ciprofloxacin-resistant isolates belonged to the
      Gammaproteobacteria class and 17 of them, 8 (7.6%) from the first sampling and 9
      (6.1%) from the second sampling, carried a qnr gene. In particular, 15 isolates
      carried the qnrS gene and 2 carried the qnrB gene. Among the qnr-positive
      isolates, 12 harboured the aac(6')-lb-cr gene and 2 of them also carried a beta
      lactamase on the same plasmid, indicating that they may be transferred
      simultaneously. It is also noteworthy that all qnr-positive isolates identified
      as Aeromonas species harboured the same qnrS allele, namely the qnrS2. This study
      reinforces the importance of environmental bacteria as vehicles for dissemination
      of antibiotic resistance genes.

PMID- 24880960
TI  - Spatial resolution measurement for iterative reconstruction by use of image
      averaging techniques in computed tomography.
AB  - The purpose of our study was to investigate the validity of a spatial resolution
      measuring method that uses a combination of a bar-pattern phantom and an image
      averaging technique, and to evaluate the spatial resolution property of iterative
      reconstruction (IR) images with middle-contrast (50 HU) objects. We used computed
      tomography (CT) images of the bar-pattern phantom reconstructed by the IR
      technology Adaptive Iterative Dose Reduction 3D (AIDR 3D), which was installed in
      the multidetector CT system Aquilion ONE (Toshiba Medical Systems, Otawara,
      Japan). The contrast of the bar-pattern image was set to 50 HU, which is
      considered to be a middle contrast that requires higher spatial resolution
      clinically. We employed an image-averaging technique to eliminate the influence
      of image noise, and we obtained averaged images of the bar-pattern phantom with
      sufficiently low noise. Modulation transfer functions (MTFs) were measured from
      the images. The conventional wire method was also used for comparison; in this
      method, AIDR 3D showed MTF values equivalent to those of filtered back
      projection. For the middle-contrast condition, the results showed that the MTF of
      AIDR 3D decreased with the strength of IR processing. Further, the MTF of AIDR 3D
      decreased with dose reduction. The image-averaging technique used was effective
      for correct evaluation of the spatial resolution for middle-contrast objects in
      IR images. The results obtained by our method clarified that the resolution
      preservation of AIDR 3D was not sufficient for middle-contrast objects.

PMID- 24880962
TI  - No evidence of neuroprotection? Perhaps not...perhaps so.

PMID- 24880961
TI  - Efficacy and safety of adalimumab for the Crohn's disease: a systematic review
      and meta-analysis of published randomized placebo-controlled trials.
AB  - PURPOSE: The aim of this study was to evaluate the efficacy and safety of
      adalimumab (ADA) for Crohn's disease. METHODS: Electronic databases, including
      PubMed, Embase, the Cochrane Library, and the Science Citation Index, were
      searched to retrieve relevant trials. We estimated pooled estimates of the odds
      ratio (OR) and relevant 95% confidence interval (CI) using fixed effects model or
      random effects model as appropriate. RESULTS: Six randomized placebo-controlled
      studies met the selection criteria. Short-term clinical response/remission and
      long-term remission were better in the ADA groups than in the control groups (P <
      0.05), both in anti-TNF-naive patients and in subjects who lost their response
      and/or became intolerant to infliximab (IFX). And ADA was also effective for
      patients who were previously treated with IFX, and its efficacy in infliximab
      exposed patients was probably less than in infliximab-naive patients. In patients
      with active Crohn's disease (CD), ADA therapy was more effective than placebo for
      obtaining complete fistula closure. In comparison with placebo, ADA does not
      increase the risk of serious adverse events. CONCLUSIONS: ADA appears to be
      effective in achieving short-term clinical response/remission, long-term
      remission, and complete fistula healing in CD, including patients not manageable
      with IFX, and appears to have a favorable safety profile. A longer duration of
      follow-up and a larger number of patients are required to better assess the
      safety profile of ADA in CD.

PMID- 24880965
TI  - Classification of renal cell carcinoma subtypes: there is more than meets the
      eye.

PMID- 24880966
TI  - Development and initial psychometric properties of the Pulmonary Arterial
      Hypertension Symptom Scale (PAHSS).
AB  - AIMS: The aim of this study is to report the development and psychometric
      properties of the Pulmonary Arterial Hypertension Symptom Scale (PAHSS).
      BACKGROUND: Patients with pulmonary arterial hypertension (PAH) experience
      multiple symptoms such as dyspnea, fatigue and chest pain, yet there is no
      comprehensive, validated symptom assessment tool to date. METHODS: This study
      used a cross sectional design. Participants completed: socio-demographic and
      medical data form, the PAHSS, the Medical Outcomes Study Short Form-36 and the
      Profile of Mood States short form. RESULTS: The PAHSS contains 17 symptoms
      measured on a 0 to 10 scale. Principal components analysis demonstrated a three
      factor solution for the PAHSS: pulmonary, diffuse, and cardiac. Coefficient
      alphas were good. Statistically significant Pearson coefficients were found
      between the PAHSS and the Medical Outcomes Study Short Form-36 and the Profile of
      Mood States short form. CONCLUSION: Findings show that the PAHSS is a promising
      scale to assess symptom severity.

PMID- 24880964
TI  - Exome sequencing identifies 2 novel presenilin 1 mutations (p.L166V and p.S230R)
      in British early-onset Alzheimer's disease.
AB  - Early-onset Alzheimer's disease (EOAD) represents 1%-2% of the Alzheimer's
      disease (AD) cases, and it is generally characterized by a positive family
      history and a rapidly progressive symptomatology. Rare coding and fully penetrant
      variants in amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin
      2 (PSEN2) are the only causative mutations reported for autosomal dominant AD.
      Thus, in this study we used exome sequencing data to rapidly screen rare coding
      variability in APP, PSEN1, and PSEN2, in a British cohort composed of 47
      unrelated EOAD cases and 179 elderly controls, neuropathologically proven. We
      report 2 novel and likely pathogenic variants in PSEN1 (p.L166V and p.S230R). A
      comprehensive catalog of rare pathogenic variants in the AD Mendelian genes is
      pivotal for a premortem diagnosis of autosomal dominant EOAD and for the
      differential diagnosis with other early onset dementias such as frontotemporal
      dementia (FTD) and Creutzfeldt-Jakob disease (CJD). 

PMID- 24880967
TI  - [Effects and significance of estradiol in men].
AB  - The most important estrogen is estradiol in both men and women. In men elevated
      estradiol levels and associated metabolic disorders have been implicated in the
      development of common diseases including cardiovascular disorders, insulin
      resistance and type 2 diabetes mellitus, as increased estradiol associated with
      decreased testosterone levels increases the risk of these diseases. In this
      review the authors summarize the causes and consequences of androgen deficiency
      and estradiol excess, and they review recent studies on potential therapeutic
      strategies to correct increased estradiol levels in men.

PMID- 24880968
TI  - [Postoperative radiotherapy of breast cancer and cardiotoxicity].
AB  - Cardiac complications may present a particular problem following radiation
      treatment applied to the mediastinum and thoracic wall (and especially to the
      left breast). Exposure of the heart during radiotherapy increases the risk of
      ischemic heart disease occurring generally years after the treatment. The
      incidence of radiation cardiotoxicity depends on various factors related to
      oncological therapies and the patient (details of radiotherapy, age, gender,
      comorbidities, smoking habits, etc.). Until recently the majority of clinical
      studies reported increased cardiac morbidity in patients receiving radiation
      treatment of the chest wall and the breast. Due to modern methods, however,
      postoperative chest wall and left breast irradiation is much safer today than
      previously. In order to avoid cardiotoxicity, adherence to clinical practice
      guidelines for chemo- and targeted therapy of breast cancer, use of the most
      advanced irradiation procedures, regular monitoring of patients, and close
      cooperation between cardiologists and oncologists are all recommended.

PMID- 24880969
TI  - [Evaluation of the DIABOBHU Observational Study].
AB  - INTRODUCTION: The authors present and analyze the outcome of DIABOBHU
      observational study. The work was carried out in Hungarian type 2 diabetic
      patients whose treatment was insufficient with oral antidiabetic agents. AIM: The
      safety and efficacy of glargine insulin added to oral antidiabetic therapy
      treatment was evaluated. METHOD: Between 2008 and 2011 3955 patients were
      enrolled. After proper education, patients titrated the insulin dosage under self
      monitoring with the help of their attending physicians. During the 26-week study
      period 3 visits were included. The primary endpoint was the change of HbA1c. The
      secondary endpoints were fasting glucose levels, dose of insulin, body weight and
      body mass index, satisfaction of the patients with the treatment and the
      incidence of hypoglycemic events. RESULTS: During the study mean HbA1c decreased
      from 8.94% to 7.31%. Most patients achieved the glycemic goals with very low
      frequency of hypoglycemia. The patients did not gain weight and were satisfied
      with their treatment. CONCLUSIONS: The authors emphasize that this treatment
      based on an analogue basal insulin should be considered as an effective and safe
      therapy.

PMID- 24880970
TI  - [Infections and use of antibiotics in residents of long-term care facilities in
      Hungary].
AB  - INTRODUCTION: Healthcare associated infections and antimicrobial use are common
      among residents of long-term care facilities. Faced to the lack of standardized
      data, the European Centre for Disease Prevention and Control funded a project
      with the aim of estimating prevalence of infections and antibiotic use in
      European long-term care facilities. AIM: The aim of the authors was to present
      the results of the European survey which were obtained in Hungary. METHOD: In
      Hungary, 91 long-term care facilities with 11,823 residents participated in the
      point-prevalence survey in May, 2013. RESULTS: The prevalence of infections was
      2.1%. Skin and soft tissues infections were the most frequent (36%), followed by
      infections of the respiratory (30%) and urinary tract (21%). Antimicrobials were
      mostly prescribed for urinary tract infections (40.3%), respiratory tract
      infections (38.4%) and skin and soft tissue infections (13.2%). The most common
      antimicrobials (97.5%) belonged to the ATC J01 class of "antibacterials for
      systemic use". CONCLUSIONS: The results emphasise the need for a national
      guideline and education for good practice in long-term care facilities.

PMID- 24880971
TI  - [Intestinal bleeding and obstruction in the small intestine caused by metastatic
      thyroid angiosarcoma. Case report].
AB  - The authors present a case of a primary angiosarcoma of the thyroid gland with an
      intestinal metastasis. The 59-year-old female patient with tarry stool and anemia
      was referred to the outpatient hospital. Her past history included a thyroid
      "cold" nodule. Gastroscopy and colonoscopy failed to identify the origin of
      gastrointestinal bleeding, however, capsule endoscopy verified synchronous tumors
      in the small intestine. The distal tumor showed signs of bleeding and caused
      bowel obstruction. An urgent operation was performed and the tumorous part of the
      ileum was resected. Histology of the removed specimen indicated cleft-like spaces
      in the mucosa with CD31+ epithelial cells. Pathological report described
      metastatic epithelial angiosarcoma with an unknown origin. Before chemotherapy
      the patient underwent total thyroidectomy and histology confirmed malignancy
      similar to that found in the intestinal surgical specimens. This case seems
      particularly interesting, because bleeding from intestinal metastasis leaded to
      the diagnosis of the primary tumor located in the thyroid gland.

PMID- 24880972
TI  - [Lajos Markusovszky memorial meeting--2014].

PMID- 24880974
TI  - Knowledge exchange in public health.

PMID- 24880975
TI  - Quantification of the effects of castration on carcass and meat quality of sheep
      by meta-analysis.
AB  - After an extensive literature search, meta-analytic techniques (fixed effect,
      random effects and hierarchical Bayesian models) were applied to numerically
      describe sizes and precision of effects caused by castration of intact rams on
      several performance, carcass and meat quality response variables. According to
      random effects models, rams presented greater (P<0.05) average daily gain, loin
      muscle area (leaner carcasses) and instrumental meat tenderness (more tough),
      with lower feed conversion ratios, dressing percentages and backfat thickness
      (less carcass fat) compared to castrates. These results could be applied in
      further strategies on the use of castration in male sheep.

PMID- 24880976
TI  - Effects of subprimal type, quality grade, and aging time on display color of
      ground beef patties.
AB  - A factorial design was used to evaluate the effects of two subprimal types (chuck
      roll and knuckle), two quality grades (Premium Choice and Select), and three
      vacuum-storage aging times before processing (7, 21, and 42d) ground beef patty
      display color attributes. Patties from chuck roll and Premium Choice subprimals
      had brighter red visual color scores, less discoloration, and higher L*, a*, b*,
      and chroma values than those from knuckle and Select subprimals, respectively.
      With an increased display time, patties became darker red, more discolored, and
      had decreased L*, a*, b*, and chroma values. Therefore, aging Premium Choice
      chuck rolls for less time (fewer than 21d) could maximize display color life. 

PMID- 24880977
TI  - Rheological behaviour of commercial cooked meat products evaluated by tensile
      test and texture profile analysis (TPA).
AB  - The breaking strength (BS) and energy to fracture (EF) of commercial cooked meat
      products (CMP) manufactured from different entire pieces were determined by
      tensile test. BS and EF were related to texture profile analysis (TPA) and
      physico-chemical data. Two textural profiles were characterized mainly by BS,
      springiness adhesiveness and fat content. Multivariate regression analysis
      confirms that TPA parameters could be used to construct models to predict BS and
      EF. Therefore, just one TPA analysis will allow to obtain both TPA and tensile
      parameters, providing valuable information about mechanical behaviour to improve
      product handling at industrial level especially in sliced CMP. 

PMID- 24880978
TI  - Perceived duration decreases with increasing eccentricity.
AB  - Previous studies examining the influence of stimulus location on temporal
      perception yield inhomogeneous and contradicting results. Therefore, the aim of
      the present study is to soundly examine the effect of stimulus eccentricity. In a
      series of five experiments, subjects compared the duration of foveal disks to
      disks presented at different retinal eccentricities on the horizontal meridian.
      The results show that the perceived duration of a visual stimulus declines with
      increasing eccentricity. The effect was replicated with various stimulus orders
      (Experiments 1-3), as well as with cortically magnified stimuli (Experiments 4
      5), ruling out that the effect was merely caused by different cortical
      representation sizes. The apparent decreasing duration of stimuli with increasing
      eccentricity is discussed with respect to current models of time perception, the
      possible influence of visual attention and respective underlying physiological
      characteristics of the visual system. 

PMID- 24880979
TI  - 'What's in a name?' 'No more than when it's mine own'. Evidence from auditory
      oddball distraction.
AB  - Research of the distractor value of hearing the own name has shown that this self
      referring stimulus captures attention in an involuntary fashion and create
      distraction. The behavioral studies are few and the outcomes are not always clear
      cut. In this study the distraction by own name compared to a control name was
      investigated by using a cross-modal oddball task in two experiments. In the first
      experiment, thirty-nine participants were conducting a computerized
      categorization task while exposed to, to-be ignored own and matched control names
      (controlling for familiarity, gender and number of syllables) as unexpected
      auditory deviant stimulus (12.5% trials for each name category) and a sine wave
      tone as a standard stimulus (75% of the trials). In the second experiment,
      another group of thirty-nine participants completed the same task but with the
      additional deviant stimulus of an irrelevant word added (10% trials for each
      deviant type and 70% trials with the standard stimulus). Results showed deviant
      distraction by exposure to both the irrelevant word, own and the control name
      compared to the standard tone but no differences were found showing that the own
      name captured attention and distracted the participants more than an irrelevant
      word or a control name. The results elucidate the role of the own name as a
      potent auditory distractor and possible limitations with its theoretical
      significance for general theories of attention are discussed. 

PMID- 24880980
TI  - Ovarian dynamics in response to two modified intravaginal progesterone releasing
      device and oestradiol benzoate based ovulation synchronisation protocols designed
      for use in Brahman heifers.
AB  - The objective was to investigate the ovarian response of Brahman heifers to two
      modified ovulation synchronisation protocols developed to increase the proportion
      of normal synchronous ovulations. Experiment 1 characterised the growth of the
      ovulatory follicle in heifers (n=19) treated with an intravaginal progesterone
      releasing device (IPRD) and oestradiol benzoate (ODB), to determine the optimal
      time to induce ovulation. Using the findings from Experiment 1, Experiment 2
      investigated the effect of reducing the duration of IPRD insertion and increasing
      the interval from IPRD removal to ODB treatment (modified protocol 1 - OPO-6;
      n=20), and omitting ODB treatment at the time of IPRD insertion (modified
      protocol 2 - PO-6; n=20). An IPRD (0.78 g progesterone) was inserted at Day 0
      (OPO-8) or Day 2 (OPO-6 and PO-6) and all heifers also received 1 mg ODB i.m. Day
      8: IPRD removed + 500 MUg cloprostenol i.m. At 24 h (OPO-8) and 36 h (OPO-6 and
      PO-6) post IPRD removal: 1 mg ODB i.m. Fixed-time AI (FTAI) occurred at 54 h for
      OPO-8 and 72 h for OPO-6 and PO-6, post IPRD removal. After IPRD treatment all
      OPO-6 and OPO-8 heifers initiated a new follicular wave whereas 25% of PO-6
      heifers failed. Diameter of the dominant follicle was larger at FTAI in the PO-6
      (11.34 +/- 0.50 mm) compared to the OPO-8 protocol (9.74 +/- 0.51 mm; P<0.05),
      but similar to the OPO-6 protocol (10.52 +/- 0.51 mm). Proportion of ovulations
      occurring 12 h prior and 24 h post FTAI was similar for the PO-6 (80%) and OPO-6
      (75%) protocols but numerically lower in the OPO-8 heifers (60%). The apparent
      improvement in ovarian response in heifers treated with the modified protocols
      needs to be confirmed in larger field studies.

PMID- 24880981
TI  - Effects of Enterobacter cloacae on boar sperm quality during liquid storage at 17
      degrees C.
AB  - Contamination of fresh and extended boar sperm often occurs in farms and
      artificial insemination (AI) centres during semen collection, processing and
      storage. The presence of bacteria produces detrimental effects on boar sperm
      quality, which may cause economic losses in reproductive centres. The present
      study has evaluated for the first time how the presence of Enterobacter cloacae
      affects the preservation of boar spermatozoa in liquid storage at 15-17  degrees
      C for an 11-day period. With this purpose, extended semen samples from seven
      healthy post-pubertal boars were artificially contaminated with different
      sperm:bacterium ratios (2:1; 1:1; 1:5 and 1:10) of E. cloacae. The 1:0 ratio (non
      inoculated) served as a negative control. The most infective ratios (i.e. 1:5 and
      1:10) significantly damaged sperm motility and membrane integrity, increased
      sperm agglutination, and decreased the osmotic resistance of spermatozoa. In
      contrast, the negative impact that the lowest bacterial concentration (2:1) had
      on boar sperm quality was clearly lower. In addition, other parameters such as pH
      were also more affected at the highest infective ratios (i.e. 1:5 and 1:10),
      despite no damage being observed on sperm morphology. In conclusion, the present
      work shows that damage inflicted by the presence of E. cloacae in boar sperm
      during liquid storage at 15-17  degrees C compromises the longevity and
      fertilising ability of seminal doses when bacterial concentration is higher than
      a 1:1 ratio. Further research is warranted to address by which mechanism E.
      cloacae impairs boar sperm quality.

PMID- 24880982
TI  - Does periodontal treatment influence clinical and biochemical measures for
      rheumatoid arthritis? A systematic review and meta-analysis.
AB  - OBJECTIVE: Periodontitis is a potential risk factor for rheumatoid arthritis
      (RA). This systematic review considers the evidence for whether non-surgical
      treatment of periodontitis in RA patients has any effect on the clinical markers
      of RA disease activity. METHODS: MEDLINE/PubMed, CINAHL, DOSS, Embase, Scopus,
      Web of Knowledge, MedNar, Lilacs and ProQuest Theses and Dissertations were
      searched till September 2013 for quantitative studies examining the effect of non
      surgical periodontal treatment on disease activity of RA. The following were the
      inclusion criteria: (1) patients diagnosed with both RA and chronic
      periodontitis, aged 30 years or older; (2) no antibiotics in the past 3 months or
      periodontal treatment in the past 6 months; (3) non-surgical periodontal therapy;
      (4) age- and gender-matched control group; (5) measures of RA activity and (6)
      published in English. RESULTS: Five studies met the inclusion criteria. Non
      surgical periodontal treatment was associated with significant reductions in
      erythrocyte sedimentation rate and a trend towards a reduction in TNF-alpha
      titres and DAS scores. There was no evidence of an effect on RF, C-reactive
      protein, anti-cyclic citrullinated protein antibodies and IL-6. CONCLUSIONS:
      Based on clinical and biochemical markers, non-surgical periodontal treatment in
      individuals with periodontitis and RA could lead to improvements in markers of
      disease activity in RA. All studies had low subject numbers with the periods of
      intervention no longer than 6 months. Larger studies are required to explore the
      effect of non-surgical periodontal treatment on clinical indicators of RA, using
      more rigorous biochemical and clinical outcome measures as well as giving
      consideration to potential confounding factors of co-morbidity.

PMID- 24880983
TI  - Lactic acidosis in gastric cancer.

PMID- 24880984
TI  - Successful cetuximab therapy after failure of panitumumab rechallenge in a
      patient with metastatic colorectal cancer: restoration of drug sensitivity after
      anti-EGFR monoclonal antibody-free interval.

PMID- 24880985
TI  - TGFBR1*6A polymorphism in sporadic and familial colorectal Carcinoma: a case
      control study and systematic literature review.
AB  - BACKGROUND: The role of genetic factors in colorectal cancer pathogenesis is
      widely accepted. Polymorphisms are actually thought to play a role in the
      unexplained colorectal cancer (CRC) susceptibility. There is conflicting data
      regarding the role of the transforming growth factor beta receptor 1 polymorphism
      6A (TGFBR1*6A) in the increased incidence of CRC. PURPOSE: Our aim is to test the
      association between this polymorphism and sporadic/familial CRC in the Lebanese
      population paying attention to lead time bias in the control group. This is a
      case-control study conducted in two Lebanese hospital centers. MATERIALS AND
      METHODS: Cases were diagnosed with CRC during the period of 1 year prior to the
      study. Controls were healthy subjects aged >50 years with a history of normal
      colonoscopy during the period of 5 years prior to the beginning of the study. A
      total of 96 cases (57 sporadic/39 familial) and 97 controls were genotyped. The
      odds ratios for 6A carrier status was statistically significant for sporadic CRC,
      odds ratio (OR) = 2.314 (95 % confidence interval (CI) 1.030-5.195) but not for
      familial CRC. RESULTS: No association was found between 6A carrier status and
      mean age at diagnosis of CRC. This is the first article in the literature to
      evaluate the association between 6A polymorphism and total, sporadic, and
      familial CRC in a single study with reduction of bias in the control group.
      Results are in conjunction with other studies and meta-analysis.

PMID- 24880986
TI  - Factors associated with e-cigarette use: a national population survey of current
      and former smokers.
AB  - BACKGROUND: Few national surveys document the prevalence of e-cigarette use in
      the U.S. The existing metric to assess current use likely identifies individuals
      who have recently tried an e-cigarette but do not continue to use the product.
      PURPOSE: To document the prevalence of e-cigarette ever use, current use, and
      established use in a nationally representative survey of current and former
      cigarette smokers in the U.S. METHODS: A random sample of current and former
      cigarette smokers completed a web-based survey in June 2013 (n=2,136). Data were
      analyzed in November 2013. Multivariate logistic regression identified
      demographic and smoking-related factors associated with each use category. Point
      estimates with 95% CIs described e-cigarette use behaviors (e.g., preferred
      brand, purchasing patterns) for each group. RESULTS: Almost half of respondents
      had tried e-cigarettes (46.8%), but prevalence of established use remained low
      (3.8%). Although trial of e-cigarettes was highest among daily smokers, the odds
      of being an established e-cigarette user were greater for former smokers
      (OR=3.24, 95% CI=1.13, 9.30, p<0.05). Furthermore, e-cigarette preference and use
      patterns varied among ever, current, and established users. Established users
      reported using rechargeable e-cigarettes, having a regular brand, and using e
      cigarettes at home and in the workplace at much higher levels than the "current
      use" metric captures. CONCLUSIONS: Improved survey measures for e-cigarette use
      are needed. The identification of established e-cigarette users may provide
      insight to product features or other individual factors that are associated with
      sustained use of e-cigarettes.

PMID- 24880987
TI  - Escherichia coli strains expressing H12 antigens demonstrate an increased ability
      to attach to abiotic surfaces as compared with E. coli strains expressing H7
      antigens.
AB  - The role of Escherichia coli H antigens in hydrophobicity and attachment to
      glass, Teflon and stainless steel (SS) surfaces was investigated through
      construction of fliC knockout mutants in E. coli O157:H7, O1:H7 and O157:H12.
      Loss of FliC(H12) in E. coli O157:H12 decreased attachment to glass, Teflon and
      stainless steel surfaces (p<0.05). Complementing E. coli O157:H12 DeltafliC(H12)
      with cloned wildtype (wt) fliC(H12) restored attachment to wt levels. The loss of
      FliCH7 in E. coli O157:H7 and O1:H7 did not always alter attachment (p>0.05), but
      complementation with cloned fliC(H12), as opposed to cloned fliCH7, significantly
      increased attachment for both strains compared with wt counterparts (p<0.05).
      Hydrophobicity determined using bacterial adherence to hydrocarbons and contact
      angle measurements differed with fliC expression but was not correlated to the
      attachment to materials included in this study. Purified FliC was used to
      functionalise silicone nitride atomic force microscopy probes, which were used to
      measure adhesion forces between FliC and substrates. Although no significant
      difference in adhesion force was observed between FliC(H12) and FliCH7 probes,
      differences in force curves suggest different mechanism of attachment for
      FliC(H12) compared with FliCH7. These results indicate that E. coli strains
      expressing flagellar H12 antigens have an increased ability to attach to certain
      abiotic surfaces compared with E. coli strains expressing H7 antigens.

PMID- 24880988
TI  - Surface functionalization of titanium substrates with chitosan-lauric acid
      conjugate to enhance osteoblasts functions and inhibit bacteria adhesion.
AB  - Orthopedic implants failures are generally related to poor osseointegration
      and/or bacterial infection in clinical application. Surface functionalization of
      an implant is one promising alternative for enhancing osseointegration and/or
      reducing bacterial infection, thus ensuring the long term survival of the
      implant. In this study, titanium (Ti) substrates were surface functionalized with
      a polydopamine (PDOP) film as an intermediate layer for post-immobilization of
      chitosan-lauric acid (Chi-LA) conjugate. Chi-LA conjugate was synthesized and
      characterized by Fourier transform infrared spectroscopy (FTIR) and hydrogen
      proton nuclear magnetic resonance (NMR) spectrometer, respectively. Lauric acid
      (LA), a natural saturated fatty acid, was used mainly due to its good
      antibacterial property. Scanning electron microscopy (SEM) and water contact
      angle measurements were employed to detect the morphology changes and surface
      wettability of Ti substrates. The results suggested that Chi-LA conjugate was
      successfully immobilized onto the surfaces of Ti substrates. In vitro tests
      confirmed that the cell adhesion, cell viability, intracellular alkaline
      phosphatase activity and mineralization capacity of osteoblasts were remarkably
      improved when cultured onto Chi-LA surface functionalized Ti substrates.
      Antibacterial assay against Staphylococcus aureus (S. aureus) and Pseudomonas
      aeruginosa (P. aeruginosa) showed that the Chi-LA modified Ti substrates
      efficiently inhibited the adhesion and growth of bacteria. Overall, this study
      developed a promising approach to fabricate functional Ti-based orthopedic
      implants, which could enhance the biological functions of osteoblasts and
      concurrently reduce bacteria adhesion. 

PMID- 24880989
TI  - Selective transfection with osmotically active sorbitol modified PEI
      nanoparticles for enhanced anti-cancer gene therapy.
AB  - Polysorbitol-mediated transporter (PSMT) has been previously shown to achieve
      high transfection efficiency with minimal cytotoxicity. Polysorbitol backbone
      possesses osmotic properties and leads to enhanced cellular uptake. The PSMT/pDNA
      nanoparticles were prepared and the particle size, surface charge of the
      nanoparticles was determined for the study. PSMT delivers genes into cells by the
      caveolae mediated endocytic pathway. Caveolae expression is usually altered in
      transformed cancer cells. Transfection through the caveolae may help PSMT to
      selectively transfect cancer cells rather than normal cells. Transfection of the
      luciferase gene by PSMT was tested in various cell types including cancer cell
      lines, primary cells, and immortalized cells. Luciferase transgene expression
      mediated by PSMT was remarkably increased in HeLa cells compared to expression
      using the control carrier Lipofectamine. Moreover, the toxicity of PSMT was
      comparable to the control carrier (Lipofectamine) in the same cells. Selective
      transfection of cancer cells using PSMT was further confirmed by co-culture of
      cancer and normal cells, which showed that transgene expression was pre
      dominantly achieved in cancer cells. A functional p53 gene was also delivered
      into HeLa cells using PSMT and the selective transgene expression of p53 protein
      in cancer cells was analyzed through western blotting and confocal microscopy.
      HeLa cells transfected with PSMT/p53 plasmid nanoparticles showed cellular damage
      and apoptosis, which was confirmed through propidium iodide staining. 

PMID- 24880991
TI  - High performance thin layer chromatography (HPTLC) and high performance liquid
      chromatography (HPLC) for the qualitative and quantitative analysis of Calendula
      officinalis-advantages and limitations.
AB  - Chromatography techniques such as HPTLC and HPLC are commonly used to produce a
      chemical fingerprint of a plant to allow identification and quantify the main
      constituents within the plant. The aims of this study were to compare HPTLC and
      HPLC, for qualitative and quantitative analysis of the major constituents of
      Calendula officinalis and to investigate the effect of different extraction
      techniques on the C. officinalis extract composition from different parts of the
      plant. The results found HPTLC to be effective for qualitative analysis, however,
      HPLC was found to be more accurate for quantitative analysis. A combination of
      the two methods may be useful in a quality control setting as it would allow
      rapid qualitative analysis of herbal material while maintaining accurate
      quantification of extract composition. 

PMID- 24880990
TI  - Comparison of posterior capsule opacification in rabbit eyes receiving different
      administrations of rapamycin.
AB  - BACKGROUND: Posterior capsule opacification (PCO) is a common complication after
      cataract surgery. The purpose of this study was to determine the effects of three
      administering ways of rapamycin (RAPA) on the formation of PCO in rabbit eyes for
      12 weeks. METHODS: Eighty rabbits were divided into four groups, according to the
      different administrations of RAPA which they received. These were: (1) the
      control group, (2) the irrigation-treated group - 5 ng/ml intraoperative RAPA
      irrigation solution, (3) the eye-drop-treated group - 2 mg/ml RAPA eye drops, and
      (4) the IOL-treated group - RAPA-poly(lactic-co-glycolic) acid (PLGA) loaded on
      the surface of intraocular lens (IOLs) (RAPA-PLGA-IOLs). All right eyes were
      treated with lens extraction plus IOL implantation, receiving relative
      administrations of RAPA. RAPA concentrations in the aqueous humour were
      determined by high performance of liquid chromatography (HPLC). The anterior
      chamber (AC) response was observed through slit-lamp biomicroscopy. After 12
      weeks, the degree of PCO was determined by clinical evaluation. The histological
      sections, immunohistochemistry expression of proliferating cell nuclear antigen
      (PCNA) in the lens capsule were conducted. RESULTS: In the early period, AC
      response for both experimental and control eyes were similar. In the IOL-treated
      group, RAPA reached its peak at 25.68 +/- 0.74 MUg/ml on the 4th day, and it was
      detectable until 8 weeks afterwards. However, in the other groups, RAPA could not
      be detected all the time. Compared with other groups, in the IOL-treated group,
      PCO was greatly alleviated; only a few layers of the lens epithelial cells (LECs)
      and a little proliferative material around the posterior capsules, and a
      significantly weak expression of PCNA in the nuclei of LECs. By contrast, there
      was no significant statistical difference in eye-drop-treated or irrigation
      treated eyes and control eyes respectively. CONCLUSIONS: Intraocular RAPA-PLGA
      IOL was a promising, effective, and safe administration to prevent PCO compared
      with other methods in the rabbit PCO model.

PMID- 24880992
TI  - Towards a real time release approach for manufacturing tablets using NIR
      spectroscopy.
AB  - The aim of this study was to use the near-infrared spectroscopy (NIRS) as a
      process analytical tool to evaluate the conformity of paracetamol tablets in
      terms of four Pharmacopoeia tests (content uniformity, hardness, disintegration
      time, friability) and to control in-line blend uniformity. Tablets were
      manufactured by direct compression. Three different active pharmaceutical
      ingredient (API) concentrations were manufactured and three different compaction
      pressures were used. Intact tablets were analysed by transmission mode with NIRS
      prior to European Pharmacopoeia tests that were used as reference methods.
      Partial least square (PLS) regression was selected to build the prediction NIR
      models for content uniformity, tablet hardness and disintegration time. The
      prediction of NIR content uniformity and tablet hardness methods were validated
      using the accuracy profile approach. The values of the root mean squared error of
      calibration (RMSEC) and the root mean squared error of prediction (RMSEP) for the
      disintegration time indicated the robustness and the global accuracy of the NIR
      model. Regarding the tablet friability test, the classification was based on K
      nearest neighbours (KNN). Then tablet NIR analyses successfully allowed the
      prediction of their conformity. Compared to the time consuming Pharmacopoeia
      reference methods, the benefit of this nondestructive method is significant,
      especially for reducing batch release time. 

PMID- 24880994
TI  - An investigation of molecular dynamics simulation and molecular docking:
      interaction of citrus flavonoids and bovine beta-lactoglobulin in focus.
AB  - Citrus flavonoids are natural compounds with important health benefits. The study
      of their interaction with a transport protein, such as bovine beta-lactoglobulin
      (BLG), at the atomic level could be a valuable factor to control their transport
      to biological sites. In the present study, molecular docking and molecular
      dynamics simulation methods were used to investigate the interaction of
      hesperetin, naringenin, nobiletin and tangeretin as citrus flavonoids and BLG as
      transport protein. The molecular docking results revealed that these flavonoids
      bind in the internal cavity of BLG and the BLG affinity for binding the
      flavonoids follows naringenin>hesperetin>tangeretin>nobiletin. The docking
      results also indicated that the BLG-flavonoid complexes are stabilized through
      hydrophobic interactions, hydrogen bond interactions and pi-pi stacking
      interactions. The analysis of molecular dynamics (MD) simulation trajectories
      showed that the root mean square deviation (RMSD) of various systems reaches
      equilibrium and fluctuates around the mean value at various times. Time evolution
      of the radius of gyration, total solvent accessible surface of the protein and
      the second structure of protein showed as well that BLG and BLG-flavonoid
      complexes were stable around 2500ps, and there was not any conformational change
      as for BLG-flavonoid complexes. Further, the profiles of atomic fluctuations
      indicated the rigidity of the ligand binding site during the simulation. 

PMID- 24880993
TI  - A novel quantitative morphometry approach to assess regeneration in dystrophic
      skeletal muscle.
AB  - Duchenne muscular dystrophy is an inherited degenerative muscle disease with
      progressive weakness of skeletal and cardiac muscle. Disturbed calcium
      homeostasis and signalling pathways result in degeneration/regeneration cycles
      with fibrotic remodelling of muscle tissue, sustained by chronic inflammation. In
      addition to altered microarchitecture, regeneration in dystrophic muscle fibres
      is often only classified by centrally located nuclei but correlation of the
      regeneration process to nuclear volumes, myosin amounts, architecture and
      functional quality are missing, in particular in old muscles where the
      regenerative capacity is exhausted. Such information could yield novel
      regeneration-to-function biomarkers. Here we used second harmonic generation and
      multi photon fluorescence microscopy in intact single muscle fibres from wild
      type, dystrophic mdx and transgenic mdx mice expressing an Deltaex 17-48 mini
      dystrophin to determine the percentage of centronucleated fibres and nucleus-to
      myosin volume ratio as a function of age. Based on this ratio we define a
      'biomotoric efficiency' as an optical measure for fibre maturation, which is
      close to unity in adult wild-type and mini-dystrophin fibres, but smaller in very
      young and old mdx mice as a result of ongoing cell maturation (young) and
      regeneration (aged). With these parameters it is possible to provide a
      quantitative measure about muscle fibre regeneration. 

PMID- 24880996
TI  - Intelligent data analysis of instrumented gait data in stroke patients-a
      systematic review.
AB  - Instrumented gait analysis (GA) may be used to analyze the causes of gait
      deviation in stroke patients but generates a large amount of complex data. The
      task of transforming this data into a comprehensible report is cumbersome.
      Intelligent data analysis (IDA) refers to the use of computational methods in
      order to analyze quantitative data more effectively. The purpose of this review
      was to identify and appraise the available IDA methods for handling GA data
      collected from patients with stroke using the standard equipment of a gait lab
      (3D/2D motion capture, force plates, EMG). Eleven databases were systematically
      searched and fifteen studies that employed some type of IDA method for the
      analysis of kinematic and/or kinetic and/or EMG data in populations involving
      stroke patients were identified. Four categories of IDA methods were employed for
      the analysis of sensor-acquired data in these fifteen studies: classification
      methods, dimensionality reduction methods, clustering methods and expert systems.
      The methodological quality of these studies was critically appraised by examining
      sample characteristics, measurements and IDA properties. Three overall
      methodological shortcomings were identified: (1) small sample sizes and
      underreported patient characteristics, (2) testing of which method is best suited
      to the analysis was neglected and (3) lack of stringent validation procedures. No
      IDA method for GA data from stroke patients was identified that can be directly
      applied to clinical practice. Our findings suggest that the potential provided by
      IDA methods is not being fully exploited. 

PMID- 24880995
TI  - Automatic measurements of arterial input and venous output functions on cerebral
      computed tomography perfusion images: a preliminary study.
AB  - BACKGROUND: The current automatic techniques for measuring arterial input
      function (AIF) and venous output (VOF) on cerebral computed tomography perfusion
      images are prone to motion artifact and random noise, and their failure rates
      vary between 10% and 65%. We developed a new automatic technique to overcome
      these problems. METHODS: A principle axis transformation was applied to perfusion
      images to correct for translational and rotational motion artifacts. Bone voxels
      and neighboring voxels were removed from the perfusion images. Only brain voxels
      were included in the AIF and VOF measurement procedures. The selection criteria,
      such as large area under the concentration-time curve, early arrival of contrast
      agents, and narrow effective width, were used to select appropriate arterial and
      venous voxels for the AIF and VOF measurements. The proposed automatic technique
      was tested in 20 patients with unilateral cerebral arterial stenosis. The results
      of the proposed technique were compared to the results obtained by manual
      measurements and commercially available automatic selection software. RESULTS:
      The AIFs and VOFs were successfully measured using the proposed automatic
      technique in all 20 patients. The curve shapes, including the area under the
      concentration-time curve, peak concentration, time to peak, and effective width
      of the automatically measured AIFs or VOFs were comparable to that were measured
      manually. CONCLUSION: The proposed automatic measurement technique successfully
      overcomes the motion artifact and random noise problems encountered in measuring
      AIF and VOF. It can be easily integrated into software for the automatic
      calculation of cerebral blood volume and flow.

PMID- 24880997
TI  - Promoter recognition based on the maximum entropy hidden Markov model.
AB  - Since the fast development of genome sequencing has produced large scale data,
      the current work uses the bioinformatics methods to recognize different gene
      regions, such as exon, intron and promoter, which play an important role in gene
      regulations. In this paper, we introduce a new method based on the maximum
      entropy Markov model (MEMM) to recognize the promoter, which utilizes the
      biological features of the promoter for the condition. However, it leads to a
      high false positive rate (FPR). In order to reduce the FPR, we provide another
      new method based on the maximum entropy hidden Markov model (ME-HMM) without the
      independence assumption, which could also accommodate the biological features
      effectively. To demonstrate the precision, the new methods are implemented by R
      language and the hidden Markov model (HMM) is introduced for comparison. The
      experimental results show that the new methods may not only overcome the
      shortcomings of HMM, but also have their own advantages. The results indicate
      that, MEMM is excellent for identifying the conserved signals, and ME-HMM can
      demonstrably improve the true positive rate. 

PMID- 24880998
TI  - Quadcopter flight control using a low-cost hybrid interface with EEG-based
      classification and eye tracking.
AB  - We propose a wearable hybrid interface where eye movements and mental
      concentration directly influence the control of a quadcopter in three-dimensional
      space. This noninvasive and low-cost interface addresses limitations of previous
      work by supporting users to complete their complicated tasks in a constrained
      environment in which only visual feedback is provided. The combination of the two
      inputs augments the number of control commands to enable the flying robot to
      travel in eight different directions within the physical environment. Five human
      subjects participated in the experiments to test the feasibility of the hybrid
      interface. A front view camera on the hull of the quadcopter provided the only
      visual feedback to each remote subject on a laptop display. Based on the visual
      feedback, the subjects used the interface to navigate along pre-set target
      locations in the air. The flight performance was evaluated by comparing with a
      keyboard-based interface. We demonstrate the applicability of the hybrid
      interface to explore and interact with a three-dimensional physical space through
      a flying robot. 

PMID- 24880999
TI  - Is there always a need for invasive treatment of limited liver metastases in
      renal cell cancer or other solid tumors?

PMID- 24881001
TI  - A computational study on 4,7-di(furan-2-yl)benzo[c][1,2,5]thiadiazole monomer and
      its oligomers.
AB  - The energy gap, Eg, between the highest occupied molecular orbital (HOMO) and the
      lowest unoccupied molecular orbital (LUMO) energy levels that determines the
      electronic and optical properties of 4,7-di(furan-2-yl)benzo[c][1,2,5]thiadiazole
      (FSF) polymer is calculated by performing quantum chemical calculations. First,
      we theoretically investigated the most stable conformers of FSF monomer and its
      corresponding oligomers at the B3LYP/6-31G(d) and B3LYP/LANL2DZ levels of theory.
      We reveal the theoretical molecular structure of this very recently synthesized
      novel monomer and its oligomers for the first time in the literature. Our results
      from the B3LYP/6-31G(d) calculations indicated that FSF polymer has a low HOMO
      LUMO gap of 1.55 eV to be in good agreement with the experiments. Experimental
      design and synthesis of novel conjugated polymers require time-consuming and
      expensive procedures. The findings from this study are promising for the use of
      computational methods in the design of the novel conjugated polymers, and help to
      narrow the materials to be used in design and synthesis of conjugated polymers
      with desired properties. 

PMID- 24881000
TI  - Theoretical insight into the mechanism for the inhibition of the cysteine
      protease cathepsin B by 1,2,4-thiadiazole derivatives.
AB  - Several cellular disorders have been related to the overexpression of the
      cysteine protease cathepsin B (CatB), such as rheumatic arthritis, muscular
      dystrophy, osteoporosis, Alzheimer's disease, and tumor metastasis. Therefore,
      inhibiting CatB may be a way to control unregulated cellular functions and
      prevent tissue malformations. The inhibitory action of 1,2,4-thiadiazole (TDZ)
      derivatives has been associated in the literature with their ability to form
      disulfide bridges with the catalytic cysteine of CatB. In this work, we present
      molecular modeling and docking studies of a series of eight 1,2,4-thiadiazole
      compounds. Substitutions at two positions (3 and 5) on the 1,2,4-thiadiazole ring
      were analyzed, and the docking scores were correlated to experimental data. A
      correlation was found with the sequence of scores of four related compounds with
      different substituents at position 5. No correlation was observed for changes at
      position 3. In addition, quantum chemistry calculations were performed on smaller
      molecular models to study the mechanism of inhibition of TDZ at the active site
      of CatB. All possible protonation states of the ligand and the active site
      residues were assessed. The tautomeric form in which the proton is located on N2
      was identified as the species that has the structural and energetic
      characteristics that would allow the ring opening of 1,2,4-thiadiazole. 

PMID- 24881002
TI  - Franck-Condon factors using supervised artificial neural networks. I. The CF+
      cation.
AB  - Several studies of the electronic and vibrational structure of CF(+) have been
      performed since this molecule was first discovered to occur in the interstellar
      medium, and even before that. However, researchers have paid little attention to
      calculating its Franck-Condon factors (FCFs), which can aid the identification of
      this molecule through comparison with the observed intensity spectrum. In this
      work, an analysis of all of the potential energy curves of CF(+) that were
      candidates for this kind of calculation was undertaken. The Franck-Condon factors
      of CF(+) were calculated using a supervised neural network with two layers and a
      variable learning rate. 

PMID- 24881004
TI  - The personification of animals: coding of human and nonhuman body parts based on
      posture and function.
AB  - The purpose of the present research was to determine how humans represent the
      bodies and limbs of nonhuman mammals based on anatomical and functional
      properties. To this end, participants completed a series of body-part
      compatibility tasks in which they responded with a thumb or foot response to the
      color of a stimulus (red or blue, respectively) presented on different limbs of
      several animals. Across the studies, this compatibility task was conducted with
      images of human and nonhuman animals (bears, cows, and monkeys) in bipedal or
      quadrupedal postures. The results revealed that the coding of the limbs of
      nonhuman animals is strongly influenced by the posture of the body, but not the
      functional capacity of the limb. Specifically, body-part compatibility effects
      were present for both human and nonhuman animals when the figures were in a
      bipedal posture, but were not present when the animals were in a quadrupedal
      stance (Experiments 1a-c). Experiments 2a and 2b revealed that the posture-based
      body-part compatibility effects were not simply a vertical spatial compatibility
      effect or due to a mismatch between the posture of the body in the image and the
      participant. These data indicate that nonhuman animals in a bipedal posture are
      coded with respect to the "human" body representation, whereas nonhuman animals
      in a quadrupedal posture are not mapped to the human body representation.
      Overall, these studies provide new insight into the processes through which
      humans understand, mimic, and learn from the actions of nonhuman animals. 

PMID- 24881003
TI  - Early and late age of seizure onset have a differential impact on brain resting
      state organization in temporal lobe epilepsy.
AB  - Temporal lobe epilepsy (TLE) is associated with abnormalities which extend into
      the entire brain. While the age of seizure onset (SO) has a large impact on brain
      plasticity, its effect on brain connectivity at rest remains unclear, especially,
      in interaction with factors such as the presence of mesial temporal sclerosis
      (MTS). In this context, we investigated whole-brain and regional functional
      connectivity (FC) organization in 50 TLE patients who underwent a resting-state
      fMRI scan, in comparison to healthy controls, using graph-theory measures. We
      first classified TLE patients according to the presence of MTS or not. Then, we
      categorized the patients based on their age of SO into two subgroups (early or
      late age of SO). Results revealed whole-brain differences with both reduced
      functional segregation and increased integration in the patients, regardless of
      the age of SO and MTS, relative to the controls. At a local level, we revealed
      that the connectivity of the ictal hippocampus remains the most impaired for an
      early SO, even in the absence of MTS. Importantly, we showed that the impact of
      age of SO on whole-brain and regional resting-state FC depends on the presence of
      MTS. Overall, our results highlight the importance of investigating the effect of
      age of SO when examining resting-state activity in TLE, as this factor leads
      different perturbations of network modularity and connectivity at the global and
      local level, with different implications for regional plasticity and adaptive
      organization. 

PMID- 24881005
TI  - Assisting children with attention deficit hyperactivity disorder to reduce the
      hyperactive behavior of arbitrary standing in class with a Nintendo Wii remote
      controller through an active reminder and preferred reward stimulation.
AB  - Recent studies in the field of special education have shown that in combination
      with software technology, high-tech commercial products can be applied as useful
      assistive technology devices to help people with disabilities. This study
      extended this concept to turn a Nintendo Wii Remote Controller into a high
      performance limb action detector, in order to evaluate whether two students with
      Attention Deficit Hyperactivity Disorder (ADHD) could reduce their hyperactive
      behavior through an active reminder and stimulation in the form of the
      participants' preferred rewards. This study focused on one particular hyperactive
      behavior common to both students: standing up arbitrarily during class. The
      active reminder was in the form of vibration feedback provided via the built-in
      function of the Wii Remote Controller, which was controlled and triggered by a
      control system to remind participants when they were engaging in standing
      behavior. This study was performed according to a multiple baseline design across
      participants. The results showed that both participants significantly improved
      their control over their hyperactive behavior during the intervention phase, and
      retained this effective performance in the maintenance phase. The practical and
      developmental implications of the findings are discussed. 

PMID- 24881007
TI  - Assisting people with multiple disabilities to improve computer typing efficiency
      through a mouse wheel and on-screen keyboard software.
AB  - The main purpose of this study was to find out whether three students with
      multiple disabilities could increase their keyboard typing performance by poking
      the standard mouse scroll wheel with the newly developed Dynamic Typing Assistive
      Program (DTAP) and the built-in On-Screen Keyboard (OSK) computer software. The
      DTAP is a software solution that allows users to complete typing tasks with OSK
      software easily, quickly, and accurately by poking the mouse wheel. This study
      was performed according to a multiple baseline design across participants, and
      the experimental data showed that all of the participants significantly increased
      their typing efficiency in the intervention phase. Moreover, this improved
      performance was maintained during the maintenance phase. Practical and
      developmental implications of the findings were discussed. 

PMID- 24881006
TI  - Persons with moderate Alzheimer's disease use simple technology aids to manage
      daily activities and leisure occupation.
AB  - Two studies assessed technology-aided programs to support performance of daily
      activities and selection/activation of music items with patients with moderate
      Alzheimer's disease. In Study I, four patients were presented with activity
      related pictorial instructions via a computer fitted with inexpensive, commercial
      software. In Study II, four patients were (a) presented with different music
      options and (b) allowed to select and activate the preferred option via a
      microswitch response. Study I showed that each patient learned to perform the two
      activities available with percentages of correct responses exceeding 85 by the
      end of the intervention. Study II showed that all patients learned to choose and
      activate music options. Psychology students, employed in a social validation
      check, scored the patients' behavior within the program better than their
      behavior in a control situation. The relevance and usability of simplified
      pictorial-instruction programs and music choice programs for patients with
      moderate Alzheimer's disease were discussed. 

PMID- 24881008
TI  - Shifting impairment and aggression in intellectual disability and autism spectrum
      disorder.
AB  - Aggressive behaviour is a major problem in individuals with an intellectual
      disability (ID) as well as in individuals with an Autism Spectrum Disorder (ASD).
      There are indications that suggest a link between cognitive shifting and
      aggression. In this study, reports of aggressive incidents of adolescents and
      young adults with different clinical diagnoses (ID, ID+ASD, ASD) were collected
      during 1 year, using the Staff Observation Aggression Scale-Revised. Whether they
      were diagnosed with ID, ASD or both; individuals who displayed aggression were
      found to face more cognitive shifting difficulties than non-aggressive
      individuals, while no significant differences were found on severity of ASD
      symptoms. Study results support the assumption that a cognition-based model for
      aggression may be more adequate than a diagnose-based model. 

PMID- 24881009
TI  - A young patient with visual disturbance. Multiple sclerosis.

PMID- 24881010
TI  - Diffuse large B-cell lymphoma in elderly patients: a retrospective analysis.
AB  - BACKGROUND: Few data on patterns of care and outcomes are available for elderly
      patients with diffuse large B-cell lymphoma (DLBCL) outside of clinical trials.
      METHODS: We identified patients with DLBCL older than 60 years from a regional
      cancer registry between 2000 and 2010. Based on registry data and chart review,
      128 patients from the oncology network of Eastern Switzerland were analysed for
      patient characteristics, treatment and outcomes of DLBCL. Three age groups were
      compared: 60-69, 70-79 and over 80 years old. RESULTS: Median age was 73 years
      (range: 60 to 95 years). 52/121 treated patients received 6 cycles of R
      CHOP/CHOP, of those 30 (58%), 18 (35%) and 4 (7%) patients were 60-69 years, 70
      79 years or older than 80 years respectively, with a significant difference by
      age group, p=0.001. Median OS of patients 60-69, 70-79, and 80 years and older
      receiving 6 cycles of R-CHOP/CHOP were: 54 months, 31 months and 24 months
      respectively. In comparison, patients receiving other than 6 cycles of R
      CHOP/CHOP treatment regimens had a median OS of 22 months, 17 months and 6
      months, respectively. In the multivariable analysis other than 6 cycles of R
      CHOP/CHOP were significantly associated with poor survival. The risk of dying
      increased by a mean of 6% for each year of age from age 60 years onwards.
      CONCLUSION: In conclusion, treatment regimens other than 6 cycles of R-CHOP/CHOP
      were significant predictors for survival in our oncology network. The possibility
      of using R-CHOP treatment regimen should be seriously considered in elderly
      patients with DLBCL.

PMID- 24881012
TI  - Classifying syncope.
AB  - An unambiguous definition of syncope is important for care, research and teaching
      purposes. Unfortunately, many published definitions described 'syncope' as a
      broad category of transient loss of consciousness (TLOC) but still appeared to
      use a much narrower concept, creating confusion. The ESC-classification from 2001
      and subsequently distinguished between 'transient loss of consciousness', i.e.
      disorders sharing unconsciousness of short duration with a rapid and spontaneous
      recovery and syncope, the form of TLOC that is due to cerebral hypoperfusion.
      Adding the cerebral hypoperfusion element sets syncope apart from other forms of
      TLOC, mostly epileptic seizures and psychogenic attacks. We provide short
      descriptions of different forms of syncope and other forms of TLOC. 

PMID- 24881013
TI  - Driving and working with syncope.
AB  - Syncope is usually addressed in the Emergency Department (ED) by the doctor in
      charge of the clinical picture, i.e. the patient's risk is stratified, a
      diagnostic work-up is done and a prognosis is set. Patients are ultimately
      admitted to hospital or discharged. However, other aspects related to syncope may
      deeply affect their daily lives. These include how and when to return to work and
      to driving, the feelings about a recent loss of consciousness, and the potential
      relapse of syncope. This is particularly significant if the work setting is
      intrinsically hazardous. These patients need adequate clinical and psychological
      support. For patients with syncope, two main parameters should be considered
      regarding returning to work and to driving. The first is to evaluate the risk of
      syncope recurrence and the second is to consider the expected harm if syncope
      does indeed occur during these activities. In the present paper we detail the
      problem of driving (including professional driving) and work after syncope. We
      propose a new quantitative model that will guide the physician in stratifying the
      risk for patients who have had a previous syncope event. The new model considers
      the syncope recurrence risk, the job task duration, and features that facilitate
      a syncope during work. On the basis of these variables, the global risk index for
      a worker is calculated. Following appropriate validation, this method might help
      ED and occupational physicians in their decision-making process with the goal of
      safely readmitting syncope patients to the workplace. 

PMID- 24881011
TI  - The therapeutic value of targeting inflammation in gastrointestinal cancers.
AB  - Inflammation has been implicated in the initiation and progression of
      gastrointestinal (GI) cancers. Inflammation also plays important roles in
      subverting immune tolerance, escape from immune surveillance, and conferring
      resistance to chemotherapeutic agents. Targeting key regulators and mediators of
      inflammation represents an attractive strategy for GI cancer prevention and
      treatment. However, the targeting of inflammation in GI cancer is not
      straightforward and sometimes inflammation may contribute to tumor regression. We
      discuss the origins and effects of inflammation in GI cancer and how to target it
      successfully. 

PMID- 24881014
TI  - HCV RNA detection in HCV antibody-positive patients with the COBAS
      AmpliPrep/COBAS TaqMan HCV test, v2.0 in comparison with FDA-approved nucleic
      acid tests.
AB  - BACKGROUND: Analysis of hepatitis C virus (HCV) RNA levels is critical for
      assessing the efficacy of antiviral therapy and the achievement of a sustained
      virologic response. OBJECTIVE AND STUDY DESIGN: This study evaluated the clinical
      performance of the COBAS AmpliPrep/COBAS TaqMan HCV quantitative test, version
      2.0 (TAQMAN v2.0) with the COBAS AmpliPrep/COBAS TaqMan HCV quantitative test,
      version 1.0 (TAQMAN v1.0), the VERSANT HCV qualitative assay (VERSANT), and the
      COBAS AMPLICOR HCV test, v2.0 (AMPLICOR) qualitative test for the detection of
      HCV RNA in serum or EDTA plasma from patients who are or have been infected with
      HCV and carry HCV antibodies. RESULTS: A total of 277 participants were evaluable
      for the percent agreement analysis of the TAQMAN v2.0 with the VERSANT and with
      the AMPLICOR. The overall percent agreement between the TAQMAN v2.0 and the
      VERSANT or the AMPLICOR was 99.3% (95% CI: 97.4%, 99.8%) or 98.9% (95% CI: 96.9%,
      99.6%), respectively. The overall percent agreement between the TAQMAN v2.0 and
      the TAQMAN v1.0 when 267 of the original samples were assessed was 98.9% (95%
      CI=96.7%, 99.6%). CONCLUSION: The TAQMAN v2.0 demonstrated high correlation with
      the previously approved HCV RNA quantitative and qualitative tests.

PMID- 24881015
TI  - Quiet eye training improves surgical knot tying more than traditional technical
      training: a randomized controlled study.
AB  - BACKGROUND: We examined the effectiveness of technical training (TT) and quiet
      eye training (QE) on the performance of one-handed square knot tying in surgical
      residents. METHODS: Twenty surgical residents were randomly assigned to the 2
      groups and completed pretest, training, retention, and transfer tests.
      Participants wore a mobile eye tracker that simultaneously recorded their gaze
      and hand movements. Dependent variables were knot tying performance (%), QE
      duration (%), number of fixations, total movement time (s), and hand movement
      phase time (s). RESULTS: The QE training group had significantly higher
      performance scores, a longer QE duration, fewer fixations, faster total knot
      tying times, and faster movement phase times compared with the TT group. The QE
      group maintained performance in the transfer test, whereas the TT group
      significantly decreased performance from retention to transfer. CONCLUSIONS: QE
      training significantly improved learning, retention, and transfer of surgical
      knot tying compared with a traditional technical approach. Both performance
      effectiveness (performance outcome) and movement efficiency (hand movement times)
      were improved using QE modeling, instruction, and feedback.

PMID- 24881017
TI  - Perioperative outcome of esophageal fundoplication for gastroesophageal reflux
      disease in obese and morbidly obese patients.
AB  - BACKGROUND: To determine the perioperative safety of esophageal fundoplication
      for gastroesophageal reflux disease (GERD) in patients with body mass index (BMI)
      >= 35 kg/m(2). METHODS: A retrospective review of 4,231 patients who underwent
      fundoplication for GERD from 2005 to 2009 was performed. Patients were identified
      via National Surgical Quality Improvement Program and grouped by BMI < 35 versus
      BMI >= 35 kg/m(2). Univariate analysis compared 30-day outcomes. RESULTS: Of the
      4,231 patients, 3,496 (83%) had BMI < 35 kg/m(2) and 735 (17%) had BMI >= 35
      kg/m(2). Mean BMI for each cohort was 27.9 versus 39.1, respectively. Patients
      with BMI >= 35 kg/m(2) had significantly longer operative times (129.7 vs 118
      minutes, P < .0001) and increased American Society of Anesthesiologists scores
      (2.43 vs 2.3, P = .001). The overall complication rate was 1.96%. No difference
      was demonstrated by BMI in complication rate or hospital length of stay.
      Increased American Society of Anesthesiologists score, diabetes, black race,
      longer operative time, and intraoperative transfusion significantly increased
      postoperative complication rates. CONCLUSIONS: No increased risk is conferred to
      morbidly obese patients who undergo fundoplication for GERD management. This
      study identified independent patient risk factors for postoperative complication
      following esophageal fundoplication.

PMID- 24881016
TI  - Effectiveness of an absorbable fibrin sealant patch to reduce lymphoceles
      formation after axillary lymphadenectomy for breast cancer: a matched-pair
      analysis.
AB  - BACKGROUND: This study evaluated the use of TachoSil as an adjunctive therapy for
      reducing axillary lymphocele formation. METHODS: Eighty-six patients diagnosed
      with breast cancer N+ and treated with axillary lymphadenectomy received a
      TachoSil patch in the axillary wound. Using a database of patients without
      placing a hemostatic patch, we applied a matched case-control in a 1-to-2
      fashion. Multiple and logistic regression analyses were used to evaluate
      postoperative results. RESULTS: Patient group with TachoSil showed a
      significantly lower drainage volume (P < .001) and the length of stay was
      significantly shorter (P < .001). The number of patients with evacuative
      punctures was 24.5% in the group with patch versus 51.2% in the control group (P
      < .001). In multivariate analysis, the use of TachoSil was a significant
      predictor of reducing axillary drainage volume (P < .001), mean length of
      hospital stay (P = .001), and number of evacuative punctures of lymphocele (odds
      ratio .264, 95% confidence interval .144 to .484, P < .001). CONCLUSION: The use
      of TachoSil in axillary lymphadenectomy may be a safe and useful treatment option
      for reducing axillary drainage volume, incidence of symptomatic lymphocele, and
      hospital stay.

PMID- 24881018
TI  - Single-port laparoscopic treatment of small bowel obstruction.
AB  - BACKGROUND: The aim of this study was to report our initial experience with
      single-port laparoscopic surgery (SPLS) for small bowel obstruction (SBO).
      METHODS: Between October 2009 and April 2013, 36 patients underwent SPLS for SBO.
      SPLS was performed transumbilically. Patient demographics and operative and
      postoperative outcomes were analyzed. RESULTS: SPLS for SBO was successful in 35
      patients. In 1 patient, a conversion to laparotomy was required. The median
      incision length, operative time, and postoperative length of stay were 2.3 cm
      (range, 1.5 to 5.0 cm), 115 min (range, 30 to 250 min), and 8 days (range, 3 to
      26 days), respectively. The median time to resume oral intake was 3 days (range,
      1 to 16 days). The intra- and postoperative complication rates were 6% and 11%,
      respectively. CONCLUSION: SPLS was a safe and feasible therapeutic approach for
      SBO and may also be an excellent diagnostic tool when performed by an experienced
      SPLS surgeon in selected patients.

PMID- 24881019
TI  - Local access to care programs increase trauma patient follow-up compliance.
AB  - BACKGROUND: Inadequate follow-up of uninsured trauma patients after discharge
      remains a major challenge for trauma programs. Local access to care programs
      (LACPs) have been developed to improve access to health care to the uninsured. We
      hypothesized that enrollment in LACP would improve postdischarge follow-up of
      uninsured trauma patients. METHODS: Study population consisted of 5,830 uninsured
      trauma patients from 2006 to 2011, treated at a large urban level-I trauma
      center. Patients with burn injuries, transfers to another acute-care facility,
      and those who died or who left against medical advice were excluded. Patients who
      enrolled in our LACP were compared with those who did not to determine the
      relationship between enrollment in LACP and postdischarge follow-up, while
      controlling for injury severity, demographics, and discharge disposition.
      RESULTS: Patients in LACP were significantly more likely to schedule follow-up
      appointments after discharge (odds ratio = 1.78; 95% confidence interval, 1.51 to
      2.10) and to comply with them (odds ratio = 2.44; 95% confidence interval, 1.98
      to 2.99). However, 30-day readmission rates were similar in the 2 groups (1.1% vs
      1.9%). CONCLUSIONS: Enrollment in the LACP was associated with improved
      postdischarge follow-up but not readmissions.

PMID- 24881020
TI  - Incidence of overall complications and symptomatic tracheal stenosis is
      equivalent following open and percutaneous tracheostomy in the trauma patient.
AB  - BACKGROUND: While percutaneous tracheostomy (PT) is becoming the procedure of
      choice for elective tracheostomy, there is little late complication data. This
      study compared incidence of, and factors contributing to, tracheal stenosis
      following PT or open tracheostomy (OT). METHODS: A 10-year review was conducted
      of trauma patients undergoing tracheostomy. Data on demographics, injury
      severity, tracheostomy type, complications, and outcomes were compared between
      patients receiving PT or OT and for those with or without tracheal stenosis.
      RESULTS: Of 616 patients, 265 underwent OT and 351 underwent PT. Median injury
      severity score was higher for PT (26 vs 24, P = .010). Overall complication rate
      was not different (PT = 2.3% vs OT = 2.6%, P = .773). There were 9 tracheal
      stenosis, 4 (1.1%) from the PT group and 5 (1.9%) from the OT group (P = .509).
      Mortality was higher in OT patients (15.5% vs 9.7%, P = .030). Patients
      developing tracheal stenosis were younger (29.8 vs 45.2 years, P = .021) and had
      a longer intensive care unit length of stay (28.3 vs 18.9 days, P = .036).
      CONCLUSION: Risk of tracheal stenosis should not impact the decision to perform
      an OT or PT.

PMID- 24881022
TI  - The puzzling argument of antireflux surgery in obese patients with
      gastroesophageal reflux disease: can the excellent perioperative safety of
      antireflux surgery make up for better comprehensive long-term outcomes of
      bariatric surgery?

PMID- 24881021
TI  - Postextubation dysphagia in critically ill trauma patients. Are necessary new
      screening methods? Some practical comments.

PMID- 24881023
TI  - Feasibility, effectiveness and costs associated with a web-based follow-up
      assessment following total joint arthroplasty.
AB  - The purpose of this study was to assess the feasibility, effectiveness and costs
      of a web-based follow-up compared to in-person assessment following primary total
      hip or total knee arthroplasty. Patients who were at least 12 months
      postoperative were randomized to follow-up method. We excluded patients who had
      revision surgery, osteolysis, complications or identified radiographic issues.
      229 patients (118 Web, 111 in-person) completed the study. There were no patients
      who had an issue missed by the web-based follow-up. Patients in the web-based
      group travelled less (28.2km vs 103.7km, (P<0.01)), had lower associated costs
      ($10.45 vs $21.36, (P<0.01)) and took less time to complete (121.7min web vs
      228.7min usual). Web-based follow-up is a feasible, clinically effective
      alternative with lower associated costs than in-person clinic assessment.

PMID- 24881024
TI  - Evaluation of medial-lateral stability and functional outcome following total
      knee arthroplasty: results of a single hospital joint registry.
AB  - A precept of a successful total knee arthroplasty (TKA) would be a well balanced,
      stable knee. We analyzed the effects of medial-lateral (ML) stability on
      functional outcome at 2years post-operatively. Prospectively collected Joint
      Registry data of all unilateral primary TKAs between 2004 and March 2008 were
      used. ML stability (Group 1: <5 degrees , Group 2: 6 degrees -9 degrees , Group
      3: >=10 degrees ) was assessed by 3 independent researchers. 1500 patients
      undergoing 1507 arthroplasties were divided into their various groups. Outcome
      assessment involved range of motion (ROM) and functional outcome, using the Knee
      Society Function Score (KSS), Oxford Knee Score (OKS) and SF-36 score. At 2years,
      Group 1 patients reported significantly higher KSS (P<0.001) and SF-36 scores.
      All groups had good post-operative ROM. A stable knee (ML stability <5 degrees )
      post TKA is likely associated with significantly better functional outcome.

PMID- 24881025
TI  - The influence of lysosomal stability of silver nanomaterials on their toxicity to
      human cells.
AB  - How silver nanomaterials (Ag NMs) could induce toxicity has been debated heatedly
      by many researchers. We utilized Ag nanoclusters (Ag NCs) with the same size and
      ligand protection but different core surface speciation. Ag(+)-rich NCs (Ag(+)-R
      NCs) and their counterpart, the reduced Ag(0)-rich NCs (Ag(0)-R NCs) are
      synthesized to represent possible dichotomous stages in silver nanomaterial
      degradation process. Here we show Ag(0)-R NCs induce higher cellular toxicity
      when compared to Ag(+)-R NCs. This cellular toxicity is brought about via the
      modulation of reactive oxygen species (ROS) in cells as a result of the more
      rapid release of Ag species from Ag(0)-R NCs and subsequent oxidation into Ag(+)
      in the lysosomal compartment. The weaker Ag(0)-R bond greatly potentiated the
      release of Ag species in the acidic and enzymatic processes within the lysosomes.
      Since lysosomes are absent in bacteria, increasing silver nanomaterials stability
      may lower toxicity in mammalian cells whilst not reducing their efficacy to fight
      bacteria; this redesign can result in a safer silver nanomaterial. 

PMID- 24881026
TI  - The effect of inflammatory cell-derived MCP-1 loss on neuronal survival during
      chronic neuroinflammation.
AB  - Intracranial implants elicit neurodegeneration via the foreign body response
      (FBR) that includes BBB leakage, macrophage/microglia accumulation, and reactive
      astrogliosis, in addition to neuronal degradation that limit their useful
      lifespan. Previously, monocyte chemoattractant protein 1 (MCP-1, also CCL2),
      which plays an important role in monocyte recruitment and propagation of
      inflammation, was shown to be critical for various aspects of the FBR in a tissue
      specific manner. However, participation of MCP-1 in the brain FBR has not been
      evaluated. Here we examined the FBR to intracortical silicon implants in MCP-1 KO
      mice at 1, 2, and 8 weeks after implantation. MCP-1 KO mice had a diminished FBR
      compared to WT mice, characterized by reductions in BBB leakage,
      macrophage/microglia accumulation, and astrogliosis, and an increased neuronal
      density. Moreover, pharmacological inhibition of MCP-1 in implant-bearing WT mice
      maintained the increased neuronal density. To elucidate the relative contribution
      of microglia and macrophages, bone marrow chimeras were generated between MCP-1
      KO and WT mice. Increased neuronal density was observed only in MCP-1 knockout
      mice transplanted with MCP-1 knockout marrow, which indicates that resident cells
      in the brain are major contributors. We hypothesized that these improvements are
      the result of a phenotypic switch of the macrophages/microglia polarization
      state, which we confirmed using PCR for common activation markers. Our
      observations suggest that MCP-1 influences neuronal loss, which is integral to
      the progression of neurological disorders like Alzheimer's and Parkinson disease,
      via BBB leakage and macrophage polarization. 

PMID- 24881027
TI  - Silk as a biocohesive sacrificial binder in the fabrication of hydroxyapatite
      load bearing scaffolds.
AB  - Limitations of current clinical methods for bone repair continue to fuel the
      demand for a high strength, bioactive bone replacement material. Recent attempts
      to produce porous scaffolds for bone regeneration have been limited by the
      intrinsic weakness associated with high porosity materials. In this study,
      ceramic scaffold fabrication techniques for potential use in load-bearing bone
      repairs have been developed using naturally derived silk from Bombyx mori. Silk
      was first employed for ceramic grain consolidation during green body formation,
      and later as a sacrificial polymer to impart porosity during sintering. These
      techniques allowed preparation of hydroxyapatite (HA) scaffolds that exhibited a
      wide range of mechanical and porosity profiles, with some displaying unusually
      high compressive strength up to 152.4 +/- 9.1 MPa. Results showed that the
      scaffolds exhibited a wide range of compressive strengths and moduli (8.7 +/- 2.7
      MPa to 152.4 +/- 9.1 MPa and 0.3 +/- 0.1 GPa to 8.6 +/- 0.3 GPa) with total
      porosities of up to 62.9 +/- 2.7% depending on the parameters used for
      fabrication. Moreover, HA-silk scaffolds could be molded into large, complex
      shapes, and further machined post-sinter to generate specific three-dimensional
      geometries. Scaffolds supported bone marrow-derived mesenchymal stem cell
      attachment and proliferation, with no signs of cytotoxicity. Therefore, silk
      fabricated HA scaffolds show promise for load bearing bone repair and
      regeneration needs.

PMID- 24881029
TI  - Multi-modal transfection agent based on monodisperse magnetic nanoparticles for
      stem cell gene delivery and tracking.
AB  - Directing the controlled differentiation and tracking of stem cells is essential
      to achieve successful stem cell therapy. In this work, we describe a multi-modal
      (MR/optical) transfection agent (MTA) for efficient gene delivery and cell
      tracking of human mesenchymal stem cells (hMSCs). The MTA was synthesized through
      a facile two-step approach with 1) ligand exchange of a catechol-functionalized
      polypeptide (CFP) and 2) chemical immobilization of fluorescence labelled
      cationic polymer via aminolysis reaction. Cationic polymer-immobilized MTAs with
      size of ~40 nm exhibit greatly enhanced colloidal stability in aqueous solution.
      In addition, the MTAs were capable of binding DNA molecules for transfection. The
      MTA/pDNA complex showed relatively good transfection efficiency in hMSCs
      (compared to the commercial transfection agent, Lipofectamine) and good
      biocompatibility. MTA-treated hMSCs were successfully visualized after
      transplantation via MR and optical imaging system over 14 days. These studies
      highlight the challenges associated with the potential advantages of designing
      multi-modal nanostructured materials as tools for genetic materials delivery and
      cell-tracking in stem cell therapy.

PMID- 24881028
TI  - Heparin microparticle effects on presentation and bioactivity of bone
      morphogenetic protein-2.
AB  - Biomaterials capable of providing localized and sustained presentation of
      bioactive proteins are critical for effective therapeutic growth factor delivery.
      However, current biomaterial delivery vehicles commonly suffer from limitations
      that can result in low retention of growth factors at the site of interest or
      adversely affect growth factor bioactivity. Heparin, a highly sulfated
      glycosaminoglycan, is an attractive growth factor delivery vehicle due to its
      ability to reversibly bind positively charged proteins, provide sustained
      delivery, and maintain protein bioactivity. This study describes the fabrication
      and characterization of heparin methacrylamide (HMAm) microparticles for
      recombinant growth factor delivery. HMAm microparticles were shown to efficiently
      bind several heparin-binding growth factors (e.g. bone morphogenetic protein-2
      (BMP-2), vascular endothelial growth factor (VEGF), and basic fibroblast growth
      factor (FGF-2)), including a wide range of BMP-2 concentrations that exceeds the
      maximum binding capacity of other common growth factor delivery vehicles, such as
      gelatin. BMP-2 bioactivity was assessed on the basis of alkaline phosphatase
      (ALP) activity induced in skeletal myoblasts (C2C12). Microparticles loaded with
      BMP-2 stimulated comparable C2C12 ALP activity to soluble BMP-2 treatment,
      indicating that BMP-2-loaded microparticles retain bioactivity and potently
      elicit a functional cell response. In summary, our results suggest that heparin
      microparticles stably retain large amounts of bioactive BMP-2 for prolonged
      periods of time, and that presentation of BMP-2 via heparin microparticles can
      elicit cell responses comparable to soluble BMP-2 treatment. Consequently,
      heparin microparticles present an effective method of delivering and spatially
      retaining growth factors that could be used in a variety of systems to enable
      directed induction of cell fates and tissue regeneration. 

PMID- 24881031
TI  - Clinical characteristics and long-term prognosis in patients with chronic heart
      failure and reduced ejection fraction in China.
AB  - AIMS: Chronic heart failure with reduced ejection fraction (CHF-REF) remains a
      major public health problem with high morbidity and mortality, but the data on
      current treatment status and long-term prognosis in China were still missing.
      METHODS: Among prospectively recruited 2368 patients with CHF-REF in 10
      hospitals, 2154 patients provided complete followed data. Two aetiology subgroups
      (dilated cardiomyopathy, DCM and ischaemic cardiomyopathy, ICM) were classified.
      Clinical data and long-term prognosis were analysed. RESULTS: After a median
      follow-up of 52 months, 850 (39.46%) patients died, of whom 302 (35.53%) were
      sudden cardiac death (SCD). Unadjusted rates of all-cause mortality and SCD were
      higher in DCM than those in ICM (p<0.001 for both modes of death), but
      mortalities were comparable after adjustment for co-variables (p=0.387 and
      p=0.483 respectively). ACEIs/ARBs, aldosterone receptor antagonists, beta
      blockers and diuretics were dominant prescribed drugs with the prescription rates
      of 65.97%, 74.61%, 68.29% and 74.37% respectively. Multivariable analysis
      identified co-morbidities (eg, hypertension), NHYA class, ventricular
      tachycardia/fibrillation (VT/VF), QRS duration, left ventricular EF and
      creatinine as independent predictors of mortalities, whereas ACEIs/ARB, beta
      blockers and statins were associated with better prognosis. Survived from
      sustained VT/VF episodes had the highest predictive value for SCD (HR, 4.230; 95%
      CI, 2.500-7.157; p<0.001). The predictors for mortalities in DCM and ICM were
      different. CONCLUSIONS: Patients with CHF-REF had a poor prognosis in China
      despite being under current standard therapies, especially patients with DCM.
      Predictors for all-cause mortality and SCD might be identified for evaluating the
      prognosis of these patients.

PMID- 24881030
TI  - The correlation between peripheral leukocyte telomere length and indicators of
      cardiovascular aging.
AB  - OBJECTIVES: To investigate the relationship between telomere length in peripheral
      blood white cells and cardiovascular function in a healthy, aging Han Chinese
      population. METHODS: In 2012, peripheral blood leukocytes were obtained from 139
      healthy individuals in Beijing, China, and telomere restriction fragment (TRF)
      length was assayed using a digoxigenin-labeled hybridization probe in Southern
      blot assays. Indicators of cardiovascular function were also evaluated, including
      electrocardiograms (ECG), (RR, P, PR, QRS, ST and T intervals); blood pressure
      (BP), (SBP, DBP, PP, PPI); cardiovascular ultrasound (left ventricular ejection
      fraction, LVEF); mitral early and late diastolic peak flow velocity (MVE and
      MVA); and lipid indices (TC, TG, HDL, LDL, LCI). The relationships of these
      cardiovascular indictors to telomere length were evaluated. RESULTS: No
      correlations were found between telomere length and ECG, BP or lipid indices even
      after adjustment for age. Correlations were found between TFR length and some
      cardiovascular ultrasound indictors (D, MVEA, MVEDT, MVES, MVEL, MVEI, IMT), but
      these were not seen after adjusting for age. CONCLUSIONS: We did not find that
      leukocyte TFR length was associated with cardiovascular ultrasound indictors,
      ECG, BP, or lipid indices in this population of healthy Han Chinese individuals.
      Telomere length may serve as a genetic factor in biological aging.

PMID- 24881032
TI  - Acceleration of natural-abundance solid-state MAS NMR measurements on bone by
      paramagnetic relaxation from gadolinium-DTPA.
AB  - Reducing the data collection time without affecting the signal intensity and
      spectral resolution is one of the major challenges for the widespread application
      of multidimensional nuclear magnetic resonance (NMR) spectroscopy, especially in
      experiments conducted on complex heterogeneous biological systems such as bone.
      In most of these experiments, the NMR data collection time is ultimately governed
      by the proton spin-lattice relaxation times (T1). For over two decades,
      gadolinium(III)-DTPA (Gd-DTPA, DTPA=Diethylene triamine pentaacetic acid) has
      been one of the most widely used contrast-enhancement agents in magnetic
      resonance imaging (MRI). In this study, we demonstrate that Gd-DTPA can also be
      effectively used to enhance the longitudinal relaxation rates of protons in solid
      state NMR experiments conducted on bone without significant line-broadening and
      chemical-shift-perturbation side effects. Using bovine cortical bone samples
      incubated in different concentrations of Gd-DTPA complex, the (1)H T1 values were
      calculated from data collected by (1)H spin-inversion recovery method detected in
      natural-abundance (13)C cross-polarization magic angle spinning (CPMAS) NMR
      experiments. Our results reveal that the (1)H T1 values can be successfully
      reduced by a factor of 3.5 using as low as 10mM Gd-DTPA without reducing the
      spectral resolution and thus enabling faster data acquisition of the (13)C CPMAS
      spectra. These results obtained from (13)C-detected CPMAS experiments were
      further confirmed using (1)H-detected ultrafast MAS experiments on Gd-DTPA doped
      bone samples. This approach considerably improves the signal-to-noise ratio per
      unit time of NMR experiments applied to bone samples by reducing the experimental
      time required to acquire the same number of scans. 

PMID- 24881033
TI  - Traumatic brain injury alters long-term hippocampal neuron morphology in
      juvenile, but not immature, rats.
AB  - PURPOSE: Pediatric traumatic brain injury (TBI) represents a prominent yet
      understudied medical condition that can profoundly impact brain development. As
      the juvenile injured brain matures in the wake of neuropathological cascades
      during potentially critical periods, circuit alterations may explain neurological
      consequences, including cognitive deficits. We hypothesize that experimental
      brain injury in juvenile rats, with behavioral deficits that resolve, will lead
      to quantifiable structural changes in hippocampal neurons at chronic time points
      post-injury. METHODS: Controlled cortical impact (CCI), a model of focal TBI with
      contusion, was used to induce brain injury on post-natal day (PND) 17 juvenile
      rats. The histological consequence of TBI was quantified in regions of the
      hippocampus at post-injury day 28 (PID28) on sections stained using a variation
      of the Golgi-Cox staining method. Individual neuronal morphologies were digitized
      from the dentate gyrus (DG), CA3, and CA1 regions. RESULTS: Soma area in the
      ipsilateral injured DG and CA3 regions of the hippocampus increased significantly
      at PID28 in comparison to controls. In CA1, dendritic length and dendritic
      branching decreased significantly in comparison to controls and the contralateral
      hemisphere, without change in soma area. To extend the study, we examined
      neuronal morphology in rats with CCI at PND7. On PID28 after CCI on PND7 rats,
      CA1 neurons showed no injury-induced change in morphology, potentially indicating
      an age-dependent morphological response to injury. CONCLUSIONS: Long-lasting
      structural alterations in hippocampal neurons of brain-injured PND17 juvenile
      animals, but not PND7 immature animals, suggest differential plasticity depending
      on age-at-injury, with potential consequences for later function.

PMID- 24881034
TI  - Accessory limb with myelomeningocele: a rare case challenging previously held
      beliefs.
AB  - INTRODUCTION: There have been previous reports of intra-scapular limbs associated
      with a closed spina bifida and this has led to a causative theory. It is thought
      that these dysraphic appendages could not occur with defects of primary
      neurulation. CASE: The authors present a rare case of this abnormality associated
      with a large open myelomeningocele in a 6-day-old infant presenting to a
      paediatric neurosurgical hospital in Uganda. The appendage was removed and the
      spina bifida closed. There was significant stigma associated with such
      abnormality in this region. DISCUSSION: The first reported co-existence of these
      two lesions challenges previously held beliefs regarding the embryological origin
      of intra-scapular dysraphic appendage.

PMID- 24881035
TI  - An endolymphatic sac tumor with imaging features of aneurysmal bone cysts:
      differential diagnostic considerations.
AB  - BACKGROUND: Endolymphatic sac tumors (ELSTs) are rare, slow-growing tumors of the
      petrous bone. Despite the typical localisation, their radiological diagnosis can
      be challenging due to the variety of other tumors potentially showing similar
      features. CASE REPORT: We present a 16-year-old child with progressive hearing
      loss, vertigo, and tinnitus who had a large petrous bone lesion showing imaging
      features of both ELSTs and aneurysmal bone cysts (ABCs). The patient underwent
      preoperative embolization of the tumor-supplying vessels and subsequently a
      subtotal resection. Histological examination revealed an ELST. CONCLUSION:
      Despite the rarity of petrous bone ABCs, they should be considered as a
      differential diagnostic alternative of ELSTs due to their similar imaging
      appearance.

PMID- 24881036
TI  - Lumbar puncture requirement in acute hemiparesis: diagnosis of tuberculous
      meningitis after hemiparesis in a child.
AB  - BACKGROUND: Infections are an important acquired cause of cerebral arteriopathy.
      Tuberculous (TB) meningitis leading to infectious cerebral vasculopathy is a rare
      cause of acute hemiparesis. CASE REPORT: A 14-year-old male patient was examined
      after acute hemiparesis developing within 1 day. Neurological examination
      revealed total hemiplegia on the left side. Brain MRI findings showed bilateral
      focal T2-weighted signal hyperintensity in the subcortical and deep white matter
      regions. There were also areas of restricted diffusion in the right basal
      ganglia. Although the father had a history of pulmonary TB, the patient had not
      been given TB prophylaxis because of PPD negativity. At lumbar puncture, opening
      cerebrospinal fluid (CSF) pressure was 50 cm/H20, CSF protein 66.9 mg/dL, and
      glucose 54 mg/dL (concurrent blood glucose 93 mg/dL); 170 polymorphonuclear
      leukocytes per cubic millimeter were present in CSF. Following tests for TB,
      treatment was started immediately with four anti-TB drugs. TB PCR of CSF and acid
      fast bacteria (AFB) staining in gastric aspirate were positive. At clinical
      follow-up, the patient was able to walk with support at the end of the first
      month. CONCLUSION: Various infectious agents have been reported as causes of
      cerebral vasculopathy. TB, which affects a significant number of patients
      worldwide, should be kept in mind in terms of cerebral vascular complications.
      Lumbar puncture is essential in order to diagnose TB meningitis.

PMID- 24881038
TI  - A master class for European hematology.

PMID- 24881037
TI  - Optimal therapy for polycythemia vera and essential thrombocythemia can only be
      determined by the completion of randomized clinical trials.

PMID- 24881039
TI  - Morphology and immunophenotyping issues in the integrated diagnosis of
      hematologic disorders of elderly patients.

PMID- 24881040
TI  - Platelet count and aging.

PMID- 24881041
TI  - Clinical and genetic predictors of prognosis in myelodysplastic syndromes.
AB  - Myelodysplastic syndromes are a collection of clonal hematopoietic disorders with
      a wide range of clinical manifestations and eventual outcomes. Accurate
      prediction of a patient's prognosis is useful to define the risk posed by the
      disease and which treatment options are most appropriate. Several models have
      been created to help predict the prognosis for patients with myelodysplastic
      syndromes. The International Prognostic Scoring System (IPSS) has been the
      standard tool used to risk stratify MDS patients since its publication in 1997.
      Other models have since been created to improve upon the IPSS, including the
      recent Revised International Prognostic Scoring System. Most models include the
      presence or severity of peripheral blood cytopenias, the proportion of bone
      marrow blasts, and specific karyotype abnormalities. Other factors including age,
      performance status, co-morbidities, transfusion dependence, and molecular
      biomarkers can further refine the prediction of prognosis in some models. Novel,
      disease specific biomarkers with prognostic value in myelodysplastic syndromes
      including cell surface markers, gene expression profiles, and high resolution
      copy number analyses have been proposed but not yet adopted clinically. Somatic
      abnormalities in recurrently mutated genes are the most informative prognostic
      biomarkers not currently considered by clinical risk models. Mutations in
      specific genes have independent prognostic significance and, unlike cytogenetic
      abnormalities, are present in the majority of myelodysplastic syndrome cases.
      However, mutational information can be complex and there are challenges to its
      clinical implementation. Despite these limitations, DNA sequencing can refine the
      prediction of prognosis for myelodysplastic syndrome patients and has become
      increasingly available in the clinic where it will help improve the care of
      patients with myelodysplastic syndromes. 

PMID- 24881042
TI  - Management of chronic lymphocytic leukemia.
AB  - In the last decade, the management of chronic lymphocytic leukemia has undergone
      profound changes that have been driven by an improved understanding of the
      biology of the disease and the approval of several new drugs. Moreover, many
      novel drugs are currently under evaluation for rapid approval or have been
      approved by regulatory agencies, further broadening the available therapeutic
      armamentarium for patients with chronic lymphocytic leukemia. The use of novel
      biological and genetic parameters combined with a careful clinical evaluation
      allows us to dissect some of the heterogeneity of the disease and to distinguish
      patients with a very mild onset and course, who often will not need any
      treatment, from those with an intermediate prognosis and a third group with a
      very aggressive course (high-risk leukemia). On this background, it becomes
      increasingly challenging to select the right treatment strategy. In this paper,
      we describe our own approach to the management of different patients with chronic
      lymphocytic leukemia. 

PMID- 24881044
TI  - Comparative genomics of mammalian hibernators using gene networks.
AB  - In recent years, the study of the molecular processes involved in mammalian
      hibernation has shifted from investigating a few carefully selected candidate
      genes to large-scale analysis of differential gene expression. The availability
      of high-throughput data provides an unprecedented opportunity to ask whether
      phylogenetically distant species show similar mechanisms of genetic control, and
      how these relate to particular genes and pathways involved in the hibernation
      phenotype. In order to address these questions, we compare 11 datasets of
      differentially expressed (DE) genes from two ground squirrel species, one bat
      species, and the American black bear, as well as a list of genes extracted from
      the literature that previously have been correlated with the drastic
      physiological changes associated with hibernation. We identify several genes that
      are DE in different species, indicating either ancestral adaptations or
      evolutionary convergence. When we use a network approach to expand the original
      datasets of DE genes to large gene networks using available interactome data, a
      higher agreement between datasets is achieved. This indicates that the same key
      pathways are important for activating and maintaining the hibernation phenotype.
      Functional-term-enrichment analysis identifies several important metabolic and
      mitochondrial processes that are critical for hibernation, such as fatty acid
      beta-oxidation and mitochondrial transport. We do not detect any enrichment of
      positive selection signatures in the coding sequences of genes from the networks
      of hibernation-associated genes, supporting the hypothesis that the genetic
      processes shaping the hibernation phenotype are driven primarily by changes in
      gene regulation. 

PMID- 24881043
TI  - Heme and erythropoieis: more than a structural role.
AB  - Erythropoiesis is the biological process that consumes the highest amount of body
      iron for heme synthesis. Heme synthesis in erythroid cells is finely coordinated
      with that of alpha (alpha) and beta (beta)-globin, resulting in the production of
      hemoglobin, a tetramer of 2alpha- and 2beta-globin chains, and heme as the
      prosthetic group. Heme is not only the structural component of hemoglobin, but it
      plays multiple regulatory roles during the differentiation of erythroid
      precursors since it controls its own synthesis and regulates the expression of
      several erythroid-specific genes. Heme is synthesized in developing erythroid
      progenitors by the stage of proerythroblast, through a series of eight enzymatic
      reactions divided between mitochondria and cytosol. Defects of heme synthesis in
      the erythroid lineage result in sideroblastic anemias, characterized by
      microcytic anemia associated to mitochondrial iron overload, or in erythropoietic
      porphyrias, characterized by porphyrin deposition in erythroid cells. Here, we
      focus on the heme biosynthetic pathway and on human erythroid disorders due to
      defective heme synthesis. The regulatory role of heme during erythroid
      differentiation is discussed as well as the heme-mediated regulatory mechanisms
      that allow the orchestration of the adaptive cell response to heme deficiency. 

PMID- 24881046
TI  - Interaction of the muscarinic acetylcholine receptor M2 subtype with G protein
      Galpha(i/o) isotypes and Gbetagamma subunits as studied with the maltose-binding
      protein-M2-Galpha(i/o) fusion proteins expressed in Escherichia coli.
AB  - We expressed the fusion proteins of the muscarinic acetylcholine receptor M2
      subtype (M2 receptor) with a maltose-binding protein (MBP) and various G protein
      alpha subunits (Galpha(i1-i3/o)) at its N- and C-terminals, respectively (MBP-M2
      Galpha(i/o)), in Escherichia coli, and examined the effect of G protein betagamma
      subunits (Gbetagamma) on the receptor-Galpha interaction as assessed by agonist-
      and GDP-dependent [(35)S]GTPgammaS binding of the fusion proteins. We found that
      (i) Gbetagamma promoted both the agonist-dependent and -independent
      [(35)S]GTPgammaS binding with little effect on the guanine nucleotide-sensitive
      high-affinity agonist binding, (ii) the specific [(35)S]GTPgammaS binding
      activity was much greater for MBP-M2-Galpha(oA) than for MBP-M2-Galpha(i1-i3) in
      the absence of Gbetagamma, whereas Gbetagamma preferentially promoted the agonist
      dependent decrease in the affinity for GDP of MBP-M2-Galpha(i1-i3) rather than of
      MBP-M2-Galpha(oA), and (iii) the proportion of agonist-dependent [(35)S]GTPgammaS
      binding was roughly 50% irrespective of species of Galpha and the presence or
      absence of Gbetagamma. These results demonstrate that receptor-Galpha fusion
      proteins expressed in E. coli could be useful for studies of receptor-G
      interaction.

PMID- 24881045
TI  - Bias due to lack of patient blinding in clinical trials. A systematic review of
      trials randomizing patients to blind and nonblind sub-studies.
AB  - BACKGROUND: Blinding patients in clinical trials is a key methodological
      procedure, but the expected degree of bias due to nonblinded patients on
      estimated treatment effects is unknown. METHODS: Systematic review of randomized
      clinical trials with one sub-study (i.e. experimental vs control) involving
      blinded patients and another, otherwise identical, sub-study involving nonblinded
      patients. Within each trial, we compared the difference in effect sizes (i.e.
      standardized mean differences) between the sub-studies. A difference <0 indicates
      that nonblinded patients generated a more optimistic effect estimate. We pooled
      the differences with random-effects inverse variance meta-analysis, and explored
      reasons for heterogeneity. RESULTS: Our main analysis included 12 trials (3869
      patients). The average difference in effect size for patient-reported outcomes
      was -0.56 (95% confidence interval -0.71 to -0.41), (I(2)=60%, P=0.004), i.e.
      nonblinded patients exaggerated the effect size by an average of 0.56 standard
      deviation, but with considerable variation. Two of the 12 trials also used
      observer-reported outcomes, showing no indication of exaggerated effects due lack
      of patient blinding. There was a larger effect size difference in 10 acupuncture
      trials [-0.63 (-0.77 to -0.49)], than in the two non-acupuncture trials [-0.17 (
      0.41 to 0.07)]. Lack of patient blinding also increased attrition and use of co
      interventions: ratio of control group attrition risk 1.79 (1.18 to 2.70), and
      ratio of control group co-intervention risk 1.55 (0.99 to 2.43). CONCLUSIONS:
      This study provides empirical evidence of pronounced bias due to lack of patient
      blinding in complementary/alternative randomized clinical trials with patient
      reported outcomes.

PMID- 24881047
TI  - Reaction mechanism of Zn2+-dependent d-serine dehydratase: role of a conserved
      tyrosine residue interacting with pyridine ring nitrogen of pyridoxal 5'
      phosphate.
AB  - d-Serine dehydratase from Saccharomyces cerevisiae (Dsd1p) is a pyridoxal 5'
      phosphate (PLP)- and Zn(2+)-dependent enzyme that catalyzes the dehydration of d
      serine to yield pyruvate and ammonia. Dsd1p uses the Tyr residue (Y203) to
      interact with the pyridine nitrogen of PLP, which is a unique feature of PLP
      enzymes. To investigate the role of Y203 in catalysis, a series of Y203 mutants
      was constructed and studied. Mutant enzymes possessing a non-polar or a basic
      residue instead of Y203 (Y203F, A, S and R) exhibited substantial levels of
      catalytic activity, and among these, the Y203F mutant had the least impact on
      catalytic activity. The Y203D exhibited a 10(5)-fold decrease in enzyme activity,
      and unlike wild-type enzyme, the mutant enzyme favoured the Calpha reprotonation
      before hydroxyl group protonation. Our data show that the Y203 does not
      participate in the protonation of the pyridine nitrogen (N1) of PLP, and Dsd1p
      uses the cofactor in an N1-unprotonated state. The unprotonated N1 promotes
      elimination of the leaving group and evades Calpha reprotonation before hydroxyl
      group protonation. 

PMID- 24881049
TI  - Characterization of the breakpoints of a polymorphic inversion complex detects
      strict and broad breakpoint reuse at the molecular level.
AB  - Inversions are an integral part of structural variation within species, and they
      play a leading role in genome reorganization across species. Work at both the
      cytological and genome sequence levels has revealed heterogeneity in the
      distribution of inversion breakpoints, with some regions being recurrently used.
      Breakpoint reuse at the molecular level has mostly been assessed for fixed
      inversions through genome sequence comparison, and therefore rather broadly.
      Here, we have identified and sequenced the breakpoints of two polymorphic
      inversions-E1 and E2 that share a breakpoint-in the extant Est and E1 + 2
      chromosomal arrangements of Drosophila subobscura. The breakpoints are two medium
      sized repeated motifs that mediated the inversions by two different mechanisms:
      E1 via staggered breaks and subsequent repair and E2 via repeat-mediated ectopic
      recombination. The fine delimitation of the shared breakpoint revealed its strict
      reuse at the molecular level regardless of which was the intermediate
      arrangement. The occurrence of other rearrangements in the most proximal and
      distal extended breakpoint regions reveals the broad reuse of these regions. This
      differential degree of fragility might be related to their sharing the presence
      outside the inverted region of snoRNA-encoding genes. 

PMID- 24881048
TI  - Systematic review and meta-analysis of parent and family-based interventions for
      children and adolescents with chronic medical conditions.
AB  - OBJECTIVE: To quantify the effects of parent- and family-based psychological
      therapies for youth with common chronic medical conditions on parent and family
      outcomes (primary aim) and child outcomes (secondary aim). METHODS: MEDLINE,
      EMBASE, and PsycINFO were searched from inception to April 2013. 37 randomized
      controlled trials were included. Quality of the evidence was evaluated using
      GRADE criteria. Data were extracted on parent, family, and child outcomes.
      RESULTS: Pooled psychological therapies had a positive effect on parent behavior
      at posttreatment and follow-up; no significant improvement was observed for other
      outcome domains. Problem-solving therapy (PST) improved parent mental health and
      parent behavior at posttreatment and follow-up. There was insufficient evidence
      to evaluate cognitive-behavioral and systems therapies for many outcome domains.
      CONCLUSIONS: Parent- and family-based psychological therapies can improve parent
      outcomes, with PST emerging as particularly promising. Future research should
      incorporate consensus statements for outcomes assessment, multisite recruitment,
      and active comparator conditions.

PMID- 24881050
TI  - Molecular phylogeny, biogeography, and habitat preference evolution of
      marsupials.
AB  - Marsupials exhibit great diversity in ecology and morphology. However, compared
      with their sister group, the placental mammals, our understanding of many aspects
      of marsupial evolution remains limited. We use 101 mitochondrial genomes and data
      from 26 nuclear loci to reconstruct a dated phylogeny including 97% of extant
      genera and 58% of modern marsupial species. This tree allows us to analyze the
      evolution of habitat preference and geographic distributions of marsupial species
      through time. We found a pattern of mesic-adapted lineages evolving to use more
      arid and open habitats, which is broadly consistent with regional climate and
      environmental change. However, contrary to the general trend, several lineages
      subsequently appear to have reverted from drier to more mesic habitats.
      Biogeographic reconstructions suggest that current views on the connectivity
      between Australia and New Guinea/Wallacea during the Miocene and Pliocene need to
      be revised. The antiquity of several endemic New Guinean clades strongly suggests
      a substantially older period of connection stretching back to the Middle Miocene
      and implies that New Guinea was colonized by multiple clades almost immediately
      after its principal formation. 

PMID- 24881051
TI  - New gene evolution in the bonus-TIF1-gamma/TRIM33 family impacted the
      architecture of the vertebrate dorsal-ventral patterning network.
AB  - Uncovering how a new gene acquires its function and understanding how the
      function of a new gene influences existing genetic networks are important topics
      in evolutionary biology. Here, we demonstrate nonconservation for the embryonic
      functions of Drosophila Bonus and its newest vertebrate relative TIF1
      gamma/TRIM33. We showed previously that TIF1-gamma/TRIM33 functions as an
      ubiquitin ligase for the Smad4 signal transducer and antagonizes the Bone
      Morphogenetic Protein (BMP) signaling network underlying vertebrate dorsal
      ventral axis formation. Here, we show that Bonus functions as an agonist of the
      Decapentaplegic (Dpp) signaling network underlying dorsal-ventral axis formation
      in flies. The absence of conservation for the roles of Bonus and TIF1
      gamma/TRIM33 reveals a shift in the dorsal-ventral patterning networks of flies
      and mice, systems that were previously considered wholly conserved. The shift
      occurred when the new gene TIF1-gamma/TRIM33 replaced the function of the
      ubiquitin ligase Nedd4L in the lineage leading to vertebrates. Evidence of this
      replacement is our demonstration that Nedd4 performs the function of TIF1
      gamma/TRIM33 in flies during dorsal-ventral axis formation. The replacement
      allowed vertebrate Nedd4L to acquire novel functions as a ubiquitin ligase of
      vertebrate-specific Smad proteins. Overall our data reveal that the architecture
      of the Dpp/BMP dorsal-ventral patterning network continued to evolve in the
      vertebrate lineage, after separation from flies, via the incorporation of new
      genes. 

PMID- 24881053
TI  - Should we measure dyspnoea in everyone?

PMID- 24881052
TI  - Studying tumorigenesis through network evolution and somatic mutational
      perturbations in the cancer interactome.
AB  - Cells govern biological functions through complex biological networks.
      Perturbations to networks may drive cells to new phenotypic states, for example,
      tumorigenesis. Identifying how genetic lesions perturb molecular networks is a
      fundamental challenge. This study used large-scale human interactome data to
      systematically explore the relationship among network topology, somatic mutation,
      evolutionary rate, and evolutionary origin of cancer genes. We found the unique
      network centrality of cancer proteins, which is largely independent of gene
      essentiality. Cancer genes likely have experienced a lower evolutionary rate and
      stronger purifying selection than those of noncancer, Mendelian disease, and
      orphan disease genes. Cancer proteins tend to have ancient histories, likely
      originated in early metazoan, although they are younger than proteins encoded by
      Mendelian disease genes, orphan disease genes, and essential genes. We found that
      the protein evolutionary origin (age) positively correlates with protein
      connectivity in the human interactome. Furthermore, we investigated the network
      attacking perturbations due to somatic mutations identified from 3,268 tumors
      across 12 cancer types in The Cancer Genome Atlas. We observed a positive
      correlation between protein connectivity and the number of nonsynonymous somatic
      mutations, whereas a weaker or insignificant correlation between protein
      connectivity and the number of synonymous somatic mutations. These observations
      suggest that somatic mutational network-attacking perturbations to hub genes play
      an important role in tumor emergence and evolution. Collectively, this work has
      broad biomedical implications for both basic cancer biology and the development
      of personalized cancer therapy. 

PMID- 24881054
TI  - Impaired arm activity in COPD: a questionable goal for rehabilitation.

PMID- 24881055
TI  - Spiral computed tomography for stratification of pulmonary embolism: ready for
      prime time?

PMID- 24881056
TI  - Upfront triple therapy for pulmonary arterial hypertension: is three a crowd or
      critical mass?

PMID- 24881057
TI  - Predicting poor prognosis in COPD patients: looking for a lamp lit in the
      darkness of the night.

PMID- 24881058
TI  - Evidence-based, agreed-upon health priorities to remedy the tuberculosis
      patient's economic disaster.

PMID- 24881059
TI  - Sleep apnoea and cancer: the new challenge.

PMID- 24881060
TI  - Challenges and controversies in thoracic oncology: a new ERJ series.

PMID- 24881062
TI  - Use of tiotropium Respimat versus HandiHaler and mortality in patients with COPD.

PMID- 24881063
TI  - Use of tiotropium Respimat versus HandiHaler and mortality in patients with COPD.

PMID- 24881064
TI  - What the 4-metre gait speed measures and why it cannot replace functional
      capacity tests.

PMID- 24881065
TI  - What the 4-metre gait speed measures and why it cannot replace functional
      capacity tests.

PMID- 24881066
TI  - 6-minute walk distance as a predictor of outcome in idiopathic pulmonary
      fibrosis.

PMID- 24881067
TI  - 6-minute walk distance as a predictor of outcome in idiopathic pulmonary
      fibrosis.

PMID- 24881070
TI  - Topics in acute respiratory distress syndrome: the patient needs our tender
      loving and care.

PMID- 24881071
TI  - Climate change and respiratory diseases.

PMID- 24881072
TI  - Haemoptysis due to pulmonary venous stenosis.
AB  - Haemoptysis is a potentially life-threatening condition with the need for prompt
      diagnosis. In about 10-20% of all cases the bleeding source remains unexplained
      with the standard diagnostic approach. The aim of this article is to show the
      necessity of widening the diagnostic approach to haemoptysis with consideration
      of pulmonary venous stenosis as a possible cause of even severe haemoptysis and
      haemoptoe. A review of the literature was performed using the Medline/PubMed
      database with the terms: "pulmonary venous stenosis", "pulmonary venous
      infarction" and "haemoptysis". Further references from the case reports were
      considered. 58 case reports and case collections about patients with haemoptysis
      due to pulmonary venous stenosis were detected. This review gives an overview
      about the case reports and discusses the underlying pathophysiology and the pros
      and cons of different imaging techniques for the detection of pulmonary venous
      stenosis. Several conditions predispose to the obstruction of the mediastinal
      pulmonary veins. Clinical findings are unspecific and may be misleading.
      Pulmonary venous stenosis can be detected using several imaging techniques, yet
      three-dimensional magnetic resonance-angiography and three-dimensional contrast
      enhanced computed tomography are the most appropriate. Pulmonary venous stenosis
      should be considered in patients with haemoptysis.

PMID- 24881073
TI  - Is pesticide exposure a cause of obstructive airways disease?
AB  - A systematic review was performed to identify any associations between pesticide
      exposure and the occurrence (both prevalence and incidence) of airways disease
      (asthma and chronic obstructive pulmonary disease) and wheezing symptoms. PubMed,
      MEDLINE, Embase, Scopus, CINAHL, Google Scholar and the Cochrane Database of
      Systematic Reviews were searched between September 2010 and October 2010 for
      papers with the inclusion criteria of English language, published after 1990,
      peer-reviewed and nondietary exposure. From a total of 4390 papers identified, 42
      were included after initial assessment of content. After evaluating the included
      studies for quality, those considered to be at high risk of bias were excluded,
      leaving a total of 23 relevant papers. Results suggest that exposure to
      pesticides may be associated with prevalent asthma, but methodological issues,
      such as cross-sectional/case-control design, measurements of exposure and limited
      adjustment for confounders, limit the strength of the evidence base in this area.
      The association between pesticide exposure and asthma appears to be more evident
      and consistent in children than in adults. Exposure to pesticides may be
      associated with COPD; however, the strength of evidence for an association with
      COPD is weaker than for asthma. As the exposure metrics within each health end
      point varied across studies, no meta-analyses were carried out.

PMID- 24881075
TI  - Imaging: how to recognise idiopathic pulmonary fibrosis.
AB  - It is well known that high-resolution computed tomography (HRCT) is an essential
      component of the diagnostic pathway in idiopathic pulmonary fibrosis (IPF).
      Honeycombing, a common feature of IPF seen on HRCT, is crucial for an accurate
      diagnosis. Unfortunately, identification of honeycombing is not always
      straightforward, and there is some disagreement regarding its imaging features.
      It can be difficult to distinguish honeycombing from traction bronchiectasis and
      emphysema, although several imaging characteristics can be helpful. Recently,
      there has been an interest in expanding the use of HRCT beyond diagnosis for
      disease monitoring and prognostication, and several studies have provided
      valuable contributions in this regard. Traction bronchiectasis and the extent of
      fibrosis, for example, have been reported to be powerful prognostic predictors
      for mortality. Finally, considering the difficulties in diagnosis of "possible
      usual interstitial pneumonia", clinicians should always be aware that clinical
      factors must be considered together with HRCT in order to reach an accurate
      diagnosis and provide appropriate treatment.

PMID- 24881076
TI  - Staging of idiopathic pulmonary fibrosis: past, present and future.
AB  - Idiopathic pulmonary fibrosis (IPF) is traditionally staged with terms such as
      "mild", "severe", "early" and "advanced" based on pulmonary function tests. This
      approach allows physicians to monitor disease progression and advise patients and
      their families. However, it is not known if the stages of this model reflect
      distinct biological or clinical phenotypes and the therapeutic and prognostic
      value of this system is limited. Novel methods of IPF staging have recently been
      developed. The GAP model includes four baseline variables that were found to be
      predictive of outcome, as identified by logistic regression. These factors are:
      gender (G), age (A) and two lung physiology variables (P) (forced vital capacity
      and diffusing capacity of the lung for carbon monoxide). The clinical utility and
      accuracy of staging models may be further improved in the future by the
      integration of dynamic parameters that can be measured over time, as well as
      biological data from biomarkers which may be able to directly measure disease
      activity. The development of an evidence-based, multidimensional IPF staging
      model that builds on the current staging approaches to IPF is an important
      objective for improving the management of IPF.

PMID- 24881074
TI  - Diagnosis and management of idiopathic pulmonary fibrosis: French practical
      guidelines.
AB  - Idiopathic pulmonary fibrosis (IPF) is the most frequent chronic idiopathic
      interstitial pneumonia in adults. The management of rare diseases in France has
      been organised by a national plan for rare diseases, which endorsed a network of
      expert centres for rare diseases throughout France. This article is an overview
      of the executive summary of the French guidelines for the management of IPF, an
      initiative that emanated from the French National Reference Centre and the
      Network of Regional Competence Centres for Rare Lung Diseases. This review aims
      at providing pulmonologists with a document that: 1) combines the current
      available evidence; 2) reviews practical modalities of diagnosis and management
      of IPF; and 3) is adapted to everyday medical practice. The French practical
      guidelines result from the combined efforts of a coordination committee, a
      writing committee and a multidisciplinary review panel, following recommendations
      from the Haute Autorite de Sante. All recommendations included in this article
      received at least 90% agreement by the reviewing panel. Herein, we summarise the
      main conclusions and practical recommendations of the French guidelines.

PMID- 24881077
TI  - Current approaches to the diagnosis and treatment of idiopathic pulmonary
      fibrosis in Europe: the AIR survey.
AB  - This review presents the results of the 2013 Advancing IPF Research (AIR) survey,
      which assessed current approaches to the diagnosis and treatment of idiopathic
      pulmonary fibrosis (IPF) by experienced physicians. A total of 149 physicians,
      predominantly from European countries, replied to the 28-question survey. The
      results of the AIR survey were compared with a similar survey of 509 French
      pulmonologists conducted by the French National Reference Centre and the Network
      of Regional Competence Centres for Rare Lung Diseases. A number of positive
      findings emerged from the AIR survey, including the high level of
      multidisciplinary team involvement in both diagnosis and management. This survey,
      when taken together with the French survey, suggests that there is still a need
      to improve earlier diagnosis of IPF.

PMID- 24881078
TI  - Patient-centred management in idiopathic pulmonary fibrosis: similar themes in
      three communication models.
AB  - The progressive and highly variable course of idiopathic pulmonary fibrosis (IPF)
      can present patients and their families with various challenges at different
      points of the disease. Structured communication between the healthcare
      professional and the patient is vital to ensure the best possible support and
      treatment for the patient. While research in this area has been limited, an
      increasing number of studies are emerging that support the role of communication
      in patients with debilitating and fatal lung diseases. Communication models used
      in other conditions that share many challenges with IPF, such as cancer, provide
      important insights for developing specifically designed patient support and
      communications models in IPF. Three communication models will be described: 1)
      the patient-centred care model (for oncology); 2) the three pillars of care model
      (for IPF); and 3) the Brompton model of care (for interstitial lung disease).
      Themes common to all three models include comprehensive patient education,
      encouraged patient participation and an accessible healthcare system, all
      supported by a collaborative provider-patient relationship. The development of
      effective communication skills is an on-going process and it is recommended to
      examine communication models used in other chronic diseases.

PMID- 24881079
TI  - Management of idiopathic pulmonary fibrosis: selected case reports.
AB  - In 2011, revised international guidelines were issued jointly by the American
      Thoracic Society, the European Respiratory Society, the Japanese Respiratory
      Society and the Latin American Thoracic Association, which provide a valuable
      framework for the diagnosis and management of idiopathic pulmonary fibrosis
      (IPF). However, due to the complexity of IPF, these guidelines may not
      comprehensively account for the management of individual IPF patients in clinical
      practice. We describe three patient cases that were presented and discussed
      during the 2013 AIR: Advancing IPF Research meeting in Nice, France. These cases
      highlight the heterogeneity in the presentation, history and clinical course of
      IPF, together with expert insights regarding the diagnosis and management of IPF
      in the real-life setting. 

PMID- 24881080
TI  - Prone ventilation in acute respiratory distress syndrome.
AB  - Prone positioning has been used for many years in patients with acute lung injury
      (ALI)/acute respiratory distress syndrome (ARDS), with no clear benefit for
      patient outcome. Meta-analyses have suggested better survival in patients with an
      arterial oxygen tension (PaO2 )/inspiratory oxygen fraction (FIO2 ) ratio <100
      mmHg. A recent randomised controlled trial was performed in ARDS patients after a
      12-24 h stabilisation period and severity criteria (PaO2 /FIO2 <150 mmHg at a
      positive end-expiratory pressure >=5 cmH2O). This trial has demonstrated a
      significant reduction in mortality from 32.8% in the supine group to 16% in the
      prone group (p<0.001). The reasons for this dramatic effect are not clear but
      probably involves a reduction in ventilator-induced lung injury due to prone
      positioning, for which there is ample evidence in experimental and clinical
      studies. The aims of this article are to discuss: the rationale of prone
      positioning in patients with ALI/ARDS; the evidence of its use based on trial
      analysis; and the limitations of its use as well as the current place of prone
      positioning in the management of patients with ALI/ARDS. From the currently
      available data, prone positioning should be used as a first-line therapy in
      patients with severe ALI/ARDS. 

PMID- 24881081
TI  - Targeting European Respiratory Society Group activities: a survey of the
      Noninvasive Ventilatory Support Group.

PMID- 24881082
TI  - Chronic thromboembolic pulmonary hypertension complicating long-term cyproterone
      acetate therapy.

PMID- 24881084
TI  - Specific inhalation challenge tests for occupational asthma in Europe: a survey.

PMID- 24881083
TI  - The thoracic cage becomes flattened in the progression of pleuroparenchymal
      fibroelastosis.

PMID- 24881085
TI  - Recurrent pneumothoraces in a 65-year-old female: an unusual case of cystic lung
      disease.

PMID- 24881087
TI  - [Melanoma and non-melanoma skin cancer].

PMID- 24881088
TI  - [I. Melanoma heterogeneity and cancer stem cell].

PMID- 24881089
TI  - [II. A melanoma diagnostic support system based on hyperspectral data].

PMID- 24881086
TI  - Massive gene transfer and extensive RNA editing of a symbiotic dinoflagellate
      plastid genome.
AB  - Genome sequencing of Symbiodinium minutum revealed that 95 of 109 plastid
      associated genes have been transferred to the nuclear genome and subsequently
      expanded by gene duplication. Only 14 genes remain in plastids and occur as DNA
      minicircles. Each minicircle (1.8-3.3 kb) contains one gene and a conserved
      noncoding region containing putative promoters and RNA-binding sites. Nine types
      of RNA editing, including a novel G/U type, were discovered in minicircle
      transcripts but not in genes transferred to the nucleus. In contrast to DNA
      editing sites in dinoflagellate mitochondria, which tend to be highly conserved
      across all taxa, editing sites employed in DNA minicircles are highly variable
      from species to species. Editing is crucial for core photosystem protein
      function. It restores evolutionarily conserved amino acids and increases peptidyl
      hydropathy. It also increases protein plasticity necessary to initiate
      photosystem complex assembly. 

PMID- 24881090
TI  - [III.Solar ultraviolet light and pathogenesis of skin cancer - diagnosis,
      treatment, prevention update].

PMID- 24881091
TI  - [IV. Revised clinical practice guidelines for management of melanoma, squamous
      cell carcinoma, basal cell carcinoma and extramammary Paget's disease].

PMID- 24881092
TI  - Workers' Memorial Day - April 28, 2014.

PMID- 24881093
TI  - Author's reply: To PMID 23771365.

PMID- 24881094
TI  - Medical devices; immunology and microbiology devices; classification of dengue
      virus serological reagents. Final order.
AB  - The Food and Drug Administration (FDA) is classifying dengue virus serological
      reagents into class II (special controls). The special controls that will apply
      to the device are identified in this order, and the codified language for the
      dengue serological reagents classification will include the identification of the
      special controls that will apply to this device. The Agency is classifying the
      device into class II (special controls) because special controls, in addition to
      general controls, will provide a reasonable assurance of safety and effectiveness
      of the device.

PMID- 24881095
TI  - Microbiology devices; reclassification of nucleic acid-based systems for
      mycobacterium tuberculosis complex in respiratory specimens. Final rule.
AB  - The Food and Drug Administration (FDA) is reclassifying nucleic acid-based in
      vitro diagnostic devices for the detection of Mycobacterium tuberculosis complex
      in respiratory specimens from class III (premarket approval) into class II
      (special controls). FDA is also issuing the special controls guideline entitled
      ''Class II Special Controls Guideline: Nucleic Acid-Based In Vitro Diagnostic
      Devices for the Detection of Mycobacterium tuberculosis Complex in Respiratory
      Specimens.'' These devices are intended to be used as an aid in the diagnosis of
      pulmonary tuberculosis.

PMID- 24881096
TI  - [Improper doctors measured against the "black sheep" not yet implemented].

PMID- 24881097
TI  - [Vitamin D: free rein to soak up the sun!].

PMID- 24881098
TI  - The federal medical loss ratio rule: implications for consumers in year 2.
AB  - For the past two years, the Affordable Care Act has required health insurers to
      pay out a minimum percentage of premiums in the form of medical claims or quality
      improvement expenses--known as a medical loss ratio (MLR). Insurers with MLRs
      below the minimum must rebate the difference to consumers. This issue brief finds
      that total rebates for 2012 were $513 million, half the amount paid out in 2011,
      indicating greater compliance with the MLR rule. Spending on quality improvement
      remained low, at less than 1 percent of premiums. Insurers continued to reduce
      their administrative and sales costs, such as brokers' fees, without increasing
      profit margins, for a total reduction in overhead of $1.4 billion. In the first
      two years under this regulation, total consumer benefits related to the medical
      loss ratio--both rebates and reduced overhead--amounted to more than $3 billion.

PMID- 24881099
TI  - [German Society of Endocrinology for vitamin D supplementation "There is no
      evidence that vitamin D intake healthy benefits"].

PMID- 24881100
TI  - [Professor Siggelkow for vitamin D supplementation "I ask patients to 75
      nanomoles dosage"].

PMID- 24881101
TI  - [Traumatic atlanto-occipital dislocation in children: early recognition quick
      stabilization].

PMID- 24881102
TI  - [Treatment of cartilage. When is use of an orthosis useful?].

PMID- 24881103
TI  - [Rehabilitation following arthroscopic rotator cuff repair. Early mobilization or
      immobilization of the shoulder?].

PMID- 24881104
TI  - [First-line treatment for chronic pancreatitis with stones: extracorporeal shock
      wave lithotripsy?].

PMID- 24881105
TI  - [Metastatic recurrence of small bowel cancer in Crohn's disease].

PMID- 24881106
TI  - In vivo molecular imaging of cathepsin and matrix metalloproteinase activity
      discriminates between arthritic and osteoarthritic processes in mice.
AB  - Rheumatoid arthritis (RA) and osteoarthritis (OA) are serologically and
      clinically distinctive, but at the local level, both diseases have many molecular
      pathways in common. In vivo molecular imaging can unravel the local pathologic
      processes involved in both diseases. In this study, we investigated matrix
      metalloproteinase (MMP) and cathepsin activity during cartilage destruction, in
      an RA and an OA mouse model, using biophotonic imaging of substrate-based probes.
      Mice with collagen-induced arthritis (CIA) or destabilization of the medial
      meniscus (DMM) were imaged using near-infrared fluorescent probes, activated by
      several cathepsins or MMPs. Fluorescence signal intensity was compared to
      synovial gene expression, histology, and cartilage staining of a neoepitope of
      aggrecan cleaved by MMPs with the amino acids DIPEN. Increased cathepsin and MMP
      activity was seen during CIA, whereas the DMM model only showed increased MMP
      activity. DIPEN expression was seen only during CIA. A possible explanation can
      be differences in gene expressions; MMP3 and -13, known to produce DIPEN
      neoepitopes, were upregulated in the CIA model, whereas MMP12, known to be
      involved in elastin degradation and chemokine inhibition, was upregulated in the
      DMM model. Thus, molecular imaging showed no cathepsin activity at the time of
      cartilage damage in the DMM model, whereas both cathepsins and MMPs are active in
      the CIA model during disease progression.

PMID- 24881107
TI  - Evidence appraisal of St Julien JB, Aldrich MC, Sheng S, et al. Obesity increases
      operating room time for lobectomy in the Society of Thoracic Surgeons database.
      Ann Thorac Surg. 2012;94(6):1841-1847.

PMID- 24881108
TI  - RP Summary: Recommended practices for environmental cleaning.

PMID- 24881109
TI  - Reply: To PMID 24683661.

PMID- 24881110
TI  - Standards vs opinions.

PMID- 24881111
TI  - A needle-free reconstitution and transfer system for compounded sterile
      intravenous drug solutions in compliance with United States Pharmacopeia Chapter
      <797> standards.
AB  - Today's health-system pharmacists and those in independent practice face risks,
      including exposure to potent cytotoxic drugs via needlesticks, that are
      associated with preparing intravenous compounded sterile preparations for
      immediate use. Healthcare givers who administer such medications also risk
      exposure to needlesticks. Those hazards can be minimized when the pharmacist
      thoroughly understands and complies with current standard operating procedures
      for preparing intravenous compounded sterile preparations and the healthcare
      giver uses a needle-free system for drug reconstitution and administration. The
      components of an overall needlestick risk-reduction strategy to ensure safety in
      the preparation (and eventual administration) of intravenous compounded sterile
      preparations should therefore include the use of needle-free connection and
      administration devices as well as hand-hygiene training, aseptic technique
      competency evaluation and training, and the maximum use of commercially available
      or ready-to-use dosage forms. This article, which focuses on the pharmacist's use
      of a needle-free reconstitution and transfer system for compounded sterile
      intravenous drug solutions, uses as an example the Vial2Bag (Medimop Medical
      Projects, Ltd., [a subsidiary of West Pharmaceutical Services, Inc., Exton,
      Pennsylvania], Ra'anana, Israel), which complies with United States Pharmacopeia
      Chapter <797> standards. Features of that system are summarized for easy
      reference.

PMID- 24881112
TI  - Pharmaceutical compounding or pharmaceutical manufacturing? A regulatory
      perspective.
AB  - At one time, nearly all prescriptions were compounded preparations. There is an
      ongoing demand for compounded prescription medications because manufacturers
      cannot fulfill the needs of all individual patients. Compounding pharmacies are a
      long standing yet less frequently discussed element in the complex matrix of
      prescription drug manufacturing, distribution, and patient use. The drug shortage
      situation for many necessary and life-saving drug products is a complicating
      factor that has led to the numerous quality issues that currently plague large
      scale compounding pharmacies. The states are the primary regulator of pharmacies,
      including community drug stores, large chains, and specialty pharmacies.
      Pharmacies making and distributing drugs in a way that is outside the bounds of
      traditional pharmacy compounding are of great concern to the U.S. Food and Drug
      Administration. The U.S. Congress has recently passed the Drug Quality and
      Security Act. This legislation establishes a clear boundary between traditional
      compounders and compounding manufacturers. It clarifies a national, uniform set
      of rules for compounding manufacturers while preserving the states' primary role
      in traditional pharmacy regulation. It clarifies the U.S. Food and Drug
      Administration's authority over the compounding of human drugs while requiring
      the Agency to engage and coordinate with states to ensure the safety of
      compounded drugs.

PMID- 24881113
TI  - Compounding practices in Iran.
AB  - This article has been presented by pharmacists of the Razi Hospital Pharmacy,
      which is located within the Dermatology Center of Tehran University of Medical
      Sciences in Tehran, Iran, and by members of the staff at the Tehran University of
      Medical Sciences. Discussed within this article are the legalization and
      regulation of pharmaceutical compounding in Iran, the restrictions on
      pharmaceutical compounding, the general equipment used in Iran pharmacies, beyond
      use dating/expiration dating, the required pharmacy education, as well as
      information related specifically to Razi Hospital Pharmacy.

PMID- 24881114
TI  - IACP's continuing support of compounding pharmacists: letter to the FDA
      concerning 503B outsourcing facilities.

PMID- 24881115
TI  - Effective advertisements.

PMID- 24881117
TI  - Basics of sterile compounding: compounding by weight versus compounding by
      volume.
AB  - In compounding small volumes of sterile preparations, it is generally acceptable
      to use volumetric measurements. However, when compounding larger volumes or when
      the sterile preparation has a low concentration, it is best to compound by weight
      for greater accuracy. This article provides the procedures that can be followed
      when compounding by weight as compared to volume and provides an example of the
      steps involved in compounding 18.5 liters of progesterone 100 mg/mL injection.

PMID- 24881116
TI  - The essentials of United States Pharmacopeia Chapter <51> antimicrobial
      effectiveness testing and its application in pharmaceutical compounding.
AB  - Antimicrobial preservatives are excipients added to multi-dose containers of both
      sterile and non-sterile drug products. Antimicrobial preservatives are used
      primarily to inhibit growth of microbial contamination occurring during the
      period of use. Demonstration of antimicrobial preservative effectiveness is
      required for these functional excipients. This article reviews key factors for
      consideration in the selection of preservatives, principles of the preservative
      effectiveness test, and the significance of requirements for preservative
      effectiveness testing in the compounding practice.

PMID- 24881118
TI  - Basics of compounding: Tips and hints, part 2: compounding with solutions,
      suspensions, emulsions, and lotions.

PMID- 24881119
TI  - Chemical and physical compatibility of an intravenous solution of epinephrine
      with calcium chloride.
AB  - An infusion of epinephrine combined with calcium chloride has been used
      historically as an intravenous inotropic solution to support critically ill heart
      failure patients with severe cardiogenic shock. There is no reliable data on the
      stability of this solution beyond three hours. This study was conducted to
      evaluate the chemical and physical compatibility of epinephrine (0.032 mg/mL)
      combined with calcium chloride (4 mg/mL) in a solution for intravenous
      administration up to 26 hours at room temperature. The chemical stability of
      epinephrine was monitored by measuring epinephrine concentrations using high
      performance liquid chromatography. The physical compatibility of the mixture was
      determined by measuring spectrophotometric absorbance between 400 to 700 nm.
      Absorbance greater than 0.010 AU was considered an indicator of the presence of
      precipitation. The results showed epinephrine with calcium chloride was stable
      together in normal saline up to 26 hours at room temperature, irrespective of
      exposure to light. The absorbance of epinephrine throughout the study was less
      than 0.010 AU, indicating no significant precipitation. Conclusions indicate that
      epinephrine (0.032 mg/mL) combined with calcium chloride (4 mg/mL) in normal
      saline at room temperature is acceptably stable up to 26 hours for intravenous
      administration.

PMID- 24881120
TI  - E-prescription errors and their resolution in a community compounding pharmacy.
AB  - Despite apparent benefits, electronic prescribing systems still face numerous
      challenges. Errors associated with electronic prescriptions can often lead to
      workflow disruptions. This may be particularly disruptive in smaller, independent
      community pharmacies that may not have the staffing resources to adequately cope
      with an increase in required correspondence with prescriber offices. The
      objective of this study was to follow-up on a 2012 quality-improvement project
      evaluating electronic prescription error type, error rate, and time between error
      discovery and resolution in an independent compounding pharmacy. The study design
      was quality improvement with descriptive data. Data were collected over a four
      week period during which time the pharmacists completed a data collection form
      for each electronic prescription received that contained an error. Percentages
      were calculated for error type, error rate, and error resolution type. Using
      range, mean, and standard deviation, time until error resolution was reported. In
      the four-week study period an e-prescribing error rate of 23.2% was identified
      (32 errors identified in 138 e-prescriptions). The most frequent error was an
      invalid electronic prescription signature for a controlled substance (31.3%, n =
      10). The most commonly used error resolution method was a phone call to the
      physician (59%, n = 19). The average time to resolve the most frequent error type
      was 10.30 hours with a standard deviation of 18.18 hours. The results show a 40%
      decrease in the number of e-prescription errors identified compared to the
      quality-improvement evaluation done in the same pharmacy one year ago. E
      prescription errors continue to disrupt workflow and impede patient care but
      perhaps at a lower rate. Pharmacies should implement a quality-improvement review
      process to help identify solutions to systems issues.

PMID- 24881121
TI  - The standardization of nonsterile compounding: a study in quality control and
      assessment for hormone compounding.
AB  - Sterile and nonsterile compounding of medication has attracted much attention
      over the last few years due to the onset of various infections and negative
      compounding practices. This paper reports on the standardization of compounded
      hormones utilizing the Wiley Protocol, which provides nonsynthetic bioidentical
      estradiol, progesterone, dehydroepiandrosterone, and testosterone in a
      transdermal topical cream base for women and men in a standardized dosing
      regimen. Here, we present data from 2008 through 2012, which details the process
      of standardization and quality testing of the hormones through submission of
      random compounded samples for quality control and assessment. Pharmacies
      delivering the Wiley Protocol were required to follow the same compounding
      formulation, as well as submit random samples for quarterly testing. Sample
      concentrations were tested using high-performance liquid chromatography. We found
      that pharmacies that submitted samples had a 91% passing rating with a percent of
      target of 98.6% +/- 8.4%. It was also determined that pharmacies that prepared
      more compounded cream had a higher passing rating than those that prepared
      limited quantities. We found that standardization across multiple pharmacies
      could be achieved through quarterly testing of submitted samples by a third-party
      laboratory when following necessary procedures as defined by the Wiley Protocol.
      It was also determined that experience and training were a critical factor in the
      mixing of compounded prescriptions, with high consistency and accuracy providing
      patient safety.

PMID- 24881122
TI  - Preparation and stability evaluation of extemporaneous oral suspension of
      valsartan using commercially available tablets.
AB  - The aim of this study was to develop an extemporaneous valsartan suspension (80
      mg valsartan/5 mL) starting from commercial tablets (80-mg/ tablet). A high
      performance liquid chromatographic system was used for the analysis and
      quantification of valsartan in the samples studied. Samples of valsartan
      suspension for analysis were prepared as reported by the validated high
      performance liquid chromatographic method and the dissolution tests were
      performed according to the U.S. Food and Drug Administration's method. The high
      performance liquid chromatographic assay indicated that the 80-mg/5-mL valsartan
      suspension was stable for 30 days when stored at long-term and accelerated
      storage conditions. Valsartan release profile showed that approximately 85% of
      valsartan dissolved after 10 minutes and, accordingly, the calculation of
      similarity factor was not necessary. It is possible for the pharmacist to crush
      valsartan 80-mg tablets and prepare a suspension which has dosage flexibility
      that can be calculated according to body-surface area, kidney, and liver
      functions, without affecting the chemical stability of the active ingredient nor
      its dissolution profile and also have a cost-effective dosage form.

PMID- 24881123
TI  - Recharting your vision while remaining true to your Charter.

PMID- 24881124
TI  - Is there a role for antidepressant and antipsychotic pharmacogenetics in clinical
      practice in 2014?

PMID- 24881127
TI  - Long-term trend in pediatric antidepressant use, 1983-2007: a population-based
      study.
AB  - OBJECTIVE: Research is needed to clarify and improve our understanding of
      appropriateness and safety issues concerning antidepressant (AD) treatment. We
      explored the long-term trend in the dispensing of pediatric ADs using provincial,
      population-based data from Canada. METHODS: Data covering 22 ADs were drawn from
      the Saskatchewan Ministry of Health administrative data files in outpatient
      settings. The data were for 9 triennial years from 1983 to 2007, a 24-year
      period, for those aged 0 to 19 in the general population. Descriptive analyses
      were used. RESULTS: In 1983, 5.9 per 1000 population aged 0 to 19 were dispensed
      at least 1 AD; this decreased to 5.1 per 1000 population in 1989, and then
      increased to 15.4 per 1000 population in 2007, with a slower increase after 2004.
      Both sexes were dispensed more ADs from 1989 onwards, with females being the
      heavier users. The rate of AD use increased significantly with age, and this
      trend became more pronounced after 1998. Family physicians were the major
      prescribers and their prescriptions significantly increased from 1989 to 2004 and
      decreased in 2007. The use of selective serotonin reuptake inhibitors (SSRIs) was
      the major reason for the increase. The number of AD scripts per patient also
      increased. CONCLUSIONS: The growth in the prevalence of AD use among children and
      youth was largely caused by the use of SSRIs. The possibility of safety issues
      induced by AD use among children and adolescents, and different patterns of
      medication practice, suggest continuing education is warranted.

PMID- 24881128
TI  - Physical child abuse potential in adolescent girls: associations with
      psychopathology, maltreatment, and attitudes toward child-bearing.
AB  - OBJECTIVE: Adolescent mothers are at increased risk of mistreating their
      children. Intervening before they become pregnant would be an ideal primary
      prevention strategy. Our goal was to determine whether psychopathology, exposure
      to maltreatment, preparedness for child-bearing, substance use disorders (SUDs),
      IQ, race, and socioeconomic status were associated with the potential for child
      abuse in nonpregnant adolescent girls. METHOD: The Child Abuse Potential
      Inventory (CAPI) was administered to 195 nonpregnant girls (aged 15 to 16 years;
      54% African American) recruited from the community. Psychiatric diagnoses from a
      structured interview were used to form 4 groups: conduct disorder (CD),
      internalizing disorders (INTs; that is, depressive disorder, anxiety disorder, or
      both), CD + INTs, or no disorder. Exposure to maltreatment was assessed with the
      Childhood Trauma Questionnaire, and the Childbearing Attitudes Questionnaire
      measured maternal readiness. RESULTS: CAPI scores were positively correlated with
      all types of psychopathology, previous exposure to maltreatment, and negative
      attitudes toward child-bearing. IQ, SUDs, and demographic factors were not
      associated. Factors associated with child abuse potential interacted in complex
      ways, but the abuse potential of CD girls was high, regardless of other
      potentially protective factors. CONCLUSIONS: Our study demonstrates that
      adolescent girls who have CD or INT are at higher risk of perpetrating physical
      child abuse when they have children. However, the core features of CD may put
      this group at a particularly high risk, even in the context of possible
      protective factors. Treatment providers should consider pre-pregnant counselling
      about healthy mothering behaviours to girls with CD.

PMID- 24881129
TI  - Methamphetamine enhances the development of schizophrenia in first-degree
      relatives of patients with schizophrenia.
AB  - OBJECTIVE: Although there is some evidence that methamphetamine (MA) abuse may
      play a causative role in the development of schizophrenia, studies directly
      linking these 2 are rare. METHODS: In our study, the effect of MA abuse on the
      development of schizophrenia was investigated in 15 MA abusers who are offspring
      of patients with schizophrenia and 15 siblings of MA abusers without a history of
      drug abuse. Cognitive deficits and resting-state brain function were evaluated in
      all participants. Correlations between cognitive deficits and schizophrenia
      development were investigated. RESULTS: Significantly more cognitive impairments
      were observed in MA abusers, compared with their siblings without a history of
      drug use. Significant abnormalities in regional homogeneity (ReHo) signals were
      observed in resting brain in MA abusers. Decreased ReHo was found to be
      distributed over the bilateral cingulate gyrus, right Brodmann area 24, and
      bilateral anterior cingulate cortex. Seven MA abusers were diagnosed with
      schizophrenia, while 1 control sibling was diagnosed with schizophrenia during
      the 5-year follow-up. The cognitive scores correlated with the development of
      schizophrenia in MA abusers. CONCLUSION: Our study provides direct evidence for
      the causative role of MA use in the etiology of schizophrenia and highlights the
      role of MA-induced brain abnormalities in cognitive deficiency and development of
      schizophrenia.

PMID- 24881130
TI  - Understanding the reasons for delay to definitive surgical care of patients with
      acute appendicitis in rural South Africa.
AB  - BACKGROUND: Acute appendicitis in rural South Africa is associated with
      significant morbidity due to prolonged delays before definitive surgical care.
      OBJECTIVE: This audit aimed to quantify the delay in our healthcare system.
      METHODS: From September 2010 to September 2012, all patients with confirmed acute
      appendicitis were interviewed and asked about the onset of symptoms and
      subsequent events in the disease process. Events before and after contact with
      the healthcare system were referred to as the pre-hospital or behavioural domain
      and the in-hospital or assessment domain, respectively. RESULTS: Of the 500
      patients, 350 (70.0%) experienced a delay of>48 hours from onset of symptoms to
      definitive surgical care. The mean time before treatment for this group was 5
      days (range 3 - 7), while the mean for the group without delay was 1.6 days
      (range 1 - 2) (p<0.0001). Of 463 delays, 291 were in the behavioural domain and
      172 in the assessment domain; 178 patients (50.9%) experienced delay in the
      behavioural domain only, 59 (16.9%) in the assessment domain only, and 113
      (32.2%) in both domains. The mean ambulance transport time from the district
      hospital to the regional hospital was 4.9 hours. CONCLUSION: There are barriers
      that prevent patients with acute appendicitis from accessing care. There are also
      prolonged delays within the system once care has been accessed. Both these
      sources of delay need to be addressed by quality improvement programmes.

PMID- 24881126
TI  - Pharmacogenetics of antipsychotics.
AB  - OBJECTIVE: During the past decades, increasing efforts have been invested in
      studies to unravel the influence of genetic factors on antipsychotic (AP) dosage,
      treatment response, and occurrence of adverse effects. These studies aimed to
      improve clinical care by predicting outcome of treatment with APs and thus
      allowing for individualized treatment strategies. We highlight most important
      findings obtained through both candidate gene and genome-wide association
      studies, including pharmacokinetic and pharmacodynamic factors. METHODS: We
      reviewed studies on pharmacogenetics of AP response and adverse effects published
      on PubMed until early 2012. Owing to the high number of published studies, we
      focused our review on findings that have been replicated in independent studies
      or are supported by meta-analyses. RESULTS: Most robust findings were reported
      for associations between polymorphisms of the cytochrome P450 system, the
      dopamine and the serotonin transmitter systems, and dosage, treatment response,
      and adverse effects, such as AP-induced weight gain or tardive dyskinesia. These
      associations were either detected for specific medications or for classes of APs.
      CONCLUSION: First promising and robust results show that pharmacogenetics bear
      promise for a widespread use in future clinical practice. This will likely be
      achieved by developing algorithms that will include many genetic variants.
      However, further investigation is warranted to replicate and validate previous
      findings, as well as to identify new genetic variants involved in AP response and
      for replication of existing findings.

PMID- 24881131
TI  - Incidental cancer in multinodular goitre post thyroidectomy.
AB  - BACKGROUND: The risk of malignancy in patients with multinodular goitre (MNG) is
      approximately 7.2%. The gold standard for diagnosis of thyroid cancer is fine
      needle aspiration biopsy (FNAB). Unsuccessful, inconclusive or suspicious results
      mandate further investigations. The concern is that with a benign FNAB result
      there is no indication for surgery unless the patient has compression symptoms or
      cosmetic issues, but the risk of missed malignancy is nevertheless present.
      OBJECTIVE: To determine the prevalence and histological features of incidental
      cancers in patients who had thyroidectomy for MNG. METHOD: Records of patients
      who underwent thyroidectomy between January 2005 and December 2010 at Chris Hani
      Baragwanath Academic Hospital, Johannesburg, South Africa, were retrospectively
      reviewed. Data retrieved included demographic characteristics of the patients,
      type of thyroidectomy, thyroid function test results, FNAB cytology and final
      histology results. RESULT: A total of 166 thyroidectomies were performed on 162
      patients, the majority (139) of whom were females. The mean age was 46 years
      (range 15 - 79 years). A total of 120 pre-operative FNABs were available for
      analysis, 78 of which were suggestive of benign nodular goitre; 70 benign FNAB
      results were histologically confirmed to be MNG after thyroidectomy. Incidental
      malignancy was found in four of 70 cases of MNG (5.7%); all were papillary
      carcinomas, predominantly (75.0%) the follicular variant. CONCLUSION: The risk of
      missing cancer in patients with MNG was 5.7%. The commonest histological subtype
      of thyroid cancer found in MNG was papillary carcinoma.

PMID- 24881125
TI  - From pharmacogenetics to pharmacogenomics: the way toward the personalization of
      antidepressant treatment.
AB  - OBJECTIVE: Major depressive disorder is the most common psychiatric disorder,
      worldwide, yet response and remission rates are still unsatisfactory. The
      identification of genetic predictors of antidepressant (AD) response could
      provide a promising opportunity to improve current AD efficacy through the
      personalization of treatment. The major steps and findings along this path are
      reviewed together with their clinical implications and limitations. METHOD: We
      systematically reviewed the literature through MEDLINE and Embase database
      searches, using any word combination of "antidepressant," "gene," "polymorphism,"
      "pharmacogenetics," "genome-wide association study," "GWAS," "response," and
      "adverse drug reactions." Experimental works and reviews published until March
      2012 were collected and compared. RESULTS: Numerous genes pertaining to several
      functional systems were associated with AD response. The more robust findings
      were found for the following genes: solute carrier family 6 (neurotransmitter
      transporter), member 4; serotonin receptor 1A and 2A; brain-derived neurotrophic
      factor; and catechol-O-methyltransferase. Genome-wide association studies (GWASs)
      provided many top markers, even if none of them reached genome-wide significance.
      CONCLUSIONS: AD pharmacogenetics have not produced any knowledge applicable to
      routine clinical practice yet, as results were mainly inconsistent across
      studies. Despite this, the rising awareness about methodological deficits of past
      studies could allow for the identication of more suitable strategies, such as the
      integration of the GWAS approach with the candidate gene approach, and innovative
      methodologies, such as pathway analysis and study of depressive endophenotypes.

PMID- 24881132
TI  - Lessons from emergency laparotomy for abdominal tuberculosis in the HIV/AIDS era.
AB  - BACKGROUND: The rising incidence of HIV/AIDS has resulted in a resurgence of
      abdominal tuberculosis (TB) in HIV-positive patients in South Africa. These often
      debilitated patients frequently present with acute complications requiring
      surgery. METHODS: A prospective audit of all patients with abdominal TB
      undergoing emergency laparotomy was conducted. From January 2008 to June 2010, 49
      patients had emergency laparotomy and specimens obtained from them were
      diagnostic of TB. Twenty-five were males and 24 females, with a median age of 32
      years (range 2 - 62). Thirty-nine patients were HIV-positive (79.6%). RESULTS:
      Intra-operative findings were bowel perforations in 13 cases, small-bowel
      obstruction in seven, a frozen abdomen in ten, and enlarged lymph nodes and an
      ileocaecal mass in 19. Eleven patients (22.4%) underwent small-bowel resection
      and eight (16.3%) right hemicolectomy. Eighteen patients (36.7%) ended up with
      stomas, 14 (28.6%) had re-laparotomies, and 18 (36.7%) were admitted to the
      intensive care unit. Twenty-three patients (46.9%) required blood transfusion and
      15 (30.6%) total parenteral nutrition. Three patients (6.1%) developed an
      enterocutaneous fistula and 19 (38.8%) died. Pre-operative illness severity
      indices of acidosis, anaemia and hypo-albuminaemia were significant predictors of
      death, but mode of presentation and surgical interventions were not. CONCLUSION:
      Laparotomy as currently practised for the 'acute abdomen' in patients with
      suspected HIV and abdominal TB is associated with very high morbidity and
      mortality, which is related to pre-operative severity indices. More liberal use
      of imaging may define cases in which a more conservative approach could improve
      outcome.

PMID- 24881134
TI  - The intramyocardial left anterior descending artery: prevalence and surgical
      considerations in coronary artery bypass grafting.
AB  - BACKGROUND: Major coronary arteries usually have a subepicardial course and only
      dip into the myocardium near or at their termination. However, occasionally a
      segment of the epicardial artery may have an intramural course, and it is often
      referred to as a myocardial bridge. The left anterior descending (LAD) artery is
      the most commonly bridged vessel. Its prevalence has been evaluated at both
      autopsy and angiography. However, in the literature reviewed it is apparent that
      there are no reports of the prevalence of the intramyocardial LAD (IMLAD) artery
      in coronary artery bypass graft (CABG) series. OBJECTIVES: To document the
      prevalence of the IMLAD artery in a series of CABGs and to describe the surgical
      techniques used in these cases. METHODS: A retrospective analysis of 1349
      surgical reports of consecutive CABGs performed over a period of 23 years was
      conducted. RESULTS: An IMLAD artery was present in 293 patients (21.7%). The
      prevalence was 20.2% (51/253) in females and 22.1% (242/1096) in males. The IMLAD
      arteries extended into the interventricular septum in 3.8% (11/293) of the
      patients. CONCLUSION: An intramyocardial course of the LAD artery is relatively
      common in patients undergoing CABG and poses a challenge in bypass grafting.
      Techniques are described to address this anatomical variation when it is
      encountered at surgery.

PMID- 24881133
TI  - The role of limb perfusion studies in the paediatric ischaemic limb.
AB  - OBJECTIVES: To study the use of limb perfusion scans in children with limb
      threatening ischaemia and determine whether such scans are helpful in making
      clinical decisions. METHODS: This retrospective study compared the clinical, scan
      and surgical findings in children who had limb perfusion scans for critical limb
      ischaemia at Red Cross War Memorial Children's Hospital, Cape Town, South Africa,
      from July 2001 to December 2010. Records were reviewed and the data analysed for
      aetiology, clinical findings, limb perfusion results, operative findings and
      outcome. RESULTS: There were complete clinical and scan records for 20/22
      patients, aged 1 month to 12 years. The causes of limb ischaemia were
      meningococcal septicaemia (n = 9), septic shock (n = 6), hypovolaemic shock due
      to gastroenteritis (n = 4), and electrical burns (n = 1). The clinical, scan and
      surgical findings correlated in 40/48 imaged limbs. In one leg the findings did
      not correlate, but the perfusion scan results predicted the outcome. In the
      remaining seven cases the exact correlation was uncertain owing to technical
      difficulties or absent operative notes. CONCLUSION: This study describes a method
      for performing limb perfusion studies in children. Limb perfusion studies
      correlated well with surgical findings. These studies were useful in treatment
      decisions, parent and patient counselling and surgical planning. They
      supplemented clinical examination in assessment of the children.

PMID- 24881135
TI  - Severity of upper-limb panga injuries and infection rates associated with early
      v. late tendon repair.
AB  - BACKGROUND: Panga or machete attacks are a common cause of significant upper-limb
      trauma in South Africa. Pangas are a multipurpose household tool used
      predominantly for foraging and agricultural purposes and are highly contaminated.
      While some centres advocate immediate primary repair if no concern exists
      regarding the risk of infection, others delay definitive repair until satisfied
      there is no evidence of infection. OBJECTIVES: To compare infection rates and
      tendon re-rupture following early primary repair (within 24 h), primary repair
      after 24 h, and delayed repair following initial debridement. METHODS: We
      conducted a multicentre, retrospective, observational study of 49 patients (mean
      age 28.9 years; range 17 - 69), who were followed up for a mean of 3.4 months
      (range 0 - 8). The injuries sustained included 32 flexor tendon injuries, 14
      extensor tendon injuries, 9 fractures and 21 peripheral nerve injuries. RESULTS:
      Of the patients, 17 underwent early primary repair (within 24 h), 19 delayed
      primary repair, and 13 delayed repair following primary washout. Wounds were
      assessed postoperatively using the ASEPSIS wound scoring system and patients were
      clinically assessed for tendon rerupture. No significant differences were found
      in the comparative infection rates for early primary repair (5.9%; 1/17), delayed
      primary repair (10.5%; 2/19) and delayed repair following primary washout (23.1%;
      3/13; p=0.662). CONCLUSION: Our results indicate indicate that panga injuries can
      be repaired safely at first presentation with no increased risk of infection or
      re-rupture.

PMID- 24881136
TI  - Endometriotic stricture of the sigmoid colon presenting with intestinal
      obstruction.
AB  - Endometriosis, a relatively common condition, rarely involves the bowel; even
      more rarely does it present as a large-bowel stricture with intestinal
      obstruction. We report the case of a young woman who presented to an emergency
      department with intestinal obstruction secondary to an endometriotic stricture of
      the sigmoid colon, without evidence of disease elsewhere in the peritoneal
      cavity. Although large-bowel obstruction is usually caused by a malignant tumour,
      it can sometimes result from rare causes such as endometriosis. Symptoms of a
      cyclical nature may remind the clinician of this possibility.

PMID- 24881137
TI  - Colonic perforation following endoscopic retrograde cholangiopancreatography
      associated pancreatitis.
AB  - We highlight a potentially lethal complication of acute severe pancreatitis that
      may not be suspected in severely ill patients. A 41-year-old woman developed
      acute severe pancreatitis following endoscopic retrograde
      cholangiopancreatography (ERCP) for suspected choledocholithiasis. When her
      condition deteriorated dramatically after 2 weeks of intensive medical
      management, a computed tomography scan and water-soluble contrast enema
      examination revealed a large colonic perforation and associated collection in the
      right flank. Surgical management included an extended right hemicolectomy and a
      second laparotomy to attend to soiling at the surgical site. She survived and was
      discharged. Colonic perforation is a recognised complication of pancreatitis that
      carries a high mortality. It may result from a combination of ischaemia to the
      colon and a direct effect of noxious pancreatic enzymes. Almost all cases are
      only diagnosed at laparotomy. In view of the current trend of non-surgical
      management of pancreatitis and associated complications, colonic perforation
      should be considered in patients who deteriorate or fail to improve. To our
      knowledge this is the first case of a secure pre-operative diagnosis of colonic
      perforation due to to pancreatitis.

PMID- 24881138
TI  - Hymie Gaylis.

PMID- 24881139
TI  - [Diffuse alveolar damage DAD and organizing pneumonia OP].
AB  - Acute or subactute pulmonary damage can be either idiopathic or resulting from a
      known cause. The most common histologic types are diffuse acute alveolar damage
      (DAD) and organizing pneumonia (OP). Various kinds of infection, pulmonary drug
      reactions or acute exacerbations of interstitial lung diseases may cause DAD,
      often requiring intensive care. High-resolution computed tomography (HRTT) of the
      lungs is the most important diagnostic examination. Surgical lung biopsy is
      performed for few patients.

PMID- 24881140
TI  - [New dimensions for dendritic cells].
AB  - Dendritic cells have turned out to be important component in the regulation of
      immune responses. In addition to various external structures they recognize the
      body's own intracellular structures and utilize them to construct information
      about threats affecting the well-being of organs and tissues. Dendritic cells are
      able to direct immune responses in a manner that among other things opens new
      dimensions to the prevention and management of autoimmune diseases, allergies,
      cancer and atherosclerosis. Vaccines directed to dendritic cells and modification
      of dendritic cells in vitro are becoming a part of the novel, targeted
      immunotherapy.

PMID- 24881141
TI  - [Diagnosis and prognosis of gliomas--current prospects of molecular diagnostics].
AB  - Gliomas are tumors of the support cells of the brain and the most common of the
      primary brain tumors. Treatment of diffuse gliomas is based on surgical excision
      of the tumor and on radiotherapy and chemotherapy. The diagnosis is made in
      histopathological examination of the tumor, which today can be complemented with
      examinations involving molecular diagnostics. The most important new methods
      predicting the prognosis of glioma patients include demonstrations of the IDH
      mutation and the 1p/19q co-deletion. Profiling of gliomas may in the future allow
      tailoring of therapy in a patient-specific manner.

PMID- 24881142
TI  - [Depression and diet ].
AB  - Especially low vitamin B12 or folate and low intake of omega-3-fatty acids, but
      also low vitamin D may associate with increased risk of depression. B12 and
      folate may also be useful in the treatment of depression. The importance of
      individual fatty acids is unclear. The causal relationship between depression and
      diet, the efficacy of vitamins or dietary supplements in the treatment of
      depression, or the impact of diet compared with other treatment options need to
      be scrutinized. An overall healthy diet rich in vitamin B12, D or folate and fish
      oils may have positive effect also on depression.

PMID- 24881143
TI  - [Hodgkin's lymphoma].
AB  - Hodgkin's lymphoma is affecting young adults and having exhibited a fairly
      constant frequency over the past few years. Hodgkin's lymphoma in a young adult
      has a good prognosis, with only approximately 10% of patients dying of disease.
      Hodgkin's lymphoma in an elderly patient is more difficult to treat. Cytostatic
      chemotherapy combined with radiotherapy is the treatment of choice. New
      recommendations involve a reduced volume of radiotherapy. In long-term follow-up,
      increased numbers of new cancers and cardiovascular disease are found in patients
      having had Hodgkin's lymphoma as compared with the reference population.

PMID- 24881144
TI  - [Endometriosis-associated bowel symptoms].
AB  - BACKGROUND: In endometriosis endometrial tissue appears outside the uterine
      cavity causing dysmenorrhea, infertility, chronic abdominal pain and bowel
      symptoms. MATERIAL AND METHODS: The prevalence of bowel symptoms and the
      influence of surgical treatment of endometriosis on them were studied in 82
      patients. The data were collected from patient records and by questionnaires.
      RESULTS: At least one bowel symptom was found in 74% of patients, 73% presented
      dyschezia and 49% chronic abdominal pain. Surgical removal of endometriosis
      reduced dyschezia and diarrhea significantly (p < 0.001). CONCLUSIONS: Dyschezia,
      chronic abdominal pain and functional bowel symptoms are more common among
      patients suffering from endometriosis than in the general population. Surgery may
      relieve these symptoms.

PMID- 24881145
TI  - [Necrotizing sialometaplasia].
AB  - Necrotizing sialometaplasia is a rare inflammatory condition clinically and
      histologically resembling a malignant tumor. The lesion is usually present on the
      palatal mucosa, and heals up without treatment during a couple of months.
      Differential diagnosis is essential in order to avoid excessive therapy. We
      describe a case where an oral tumor was not a cancer after all.

PMID- 24881146
TI  - [Update on current care guidelines: chronic leg ulcers].
AB  - Chronic leg ulcer is a common disorder affecting 1.3-3.6 % of people at some time
      of their life. The etiology of the ulcer can often be identified through careful
      clinical examination. The majority of leg ulcers are caused by venous or arterial
      insufficiency. The target of ulcer treatment should always be directed to the
      cause of the ulcer. Correction of the circulatory disorder is essential for ulcer
      healing. Since the probability of ulcer healing reduces as the ulcer becomes
      chronic, effective treatment should be initiated immediately. Skin grafting
      should be considered for ulcers > 20 cm2 and > 6 months duration.

PMID- 24881147
TI  - Newcastle disease in captive falcons in the Middle East: a review of clinical and
      pathologic findings.
AB  - Newcastle disease is an important viral disease of falcons in the Middle East.
      Two different clinical presentations producing distinct clinical symptoms and
      pathologic lesions have been identified in affected falcons, denoted as
      neurotropic velogenic and viscerotropic velogenic forms. Humoral response after
      vaccination with commercially available oil-emulsion inactivated poultry vaccines
      has been observed for up to 9 months in vaccinated falcons. Public awareness
      programs at falcon medical facilities in the region are needed to promote annual
      vaccinations to prevent Newcastle disease in falcons.

PMID- 24881148
TI  - Plasma butyrylcholinesterase concentrations in psittacine birds: reference
      values, factors of variation, and association with feather-damaging behavior.
AB  - Butyrylcholinesterase is a glycoprotein enzyme used in the diagnosis of toxicosis
      by cholinesterase-inhibitor agents like organophosphates and carbamates. In
      animals, butyrylcholinesterase concentrations have been shown to vary depending
      on numerous factors such as age, sex, diet, and season of sampling. To establish
      reference values of plasma butyrylcholinesterase concentrations in common
      psittacine species, plasma butyrylcholinesterase concentrations were measured in
      1942 companion psittacine birds. The birds were classified by age, sex, season,
      health status, and the presence of feather-damaging behavior. A significant
      difference was observed among species, with eclectus parrots (Eclectus roratus)
      having the lowest and African grey parrots (Psittacus erithacus) having the
      highest reference values. Plasma butyrylcholinesterase concentrations varied by
      age, health status, and season but not by sex. Concentrations were significantly
      higher during autumn and spring than during winter and summer, and significantly
      lower in healthy birds than in sick birds. No significant association between
      butyrylcholinesterase concentrations and feather-damaging behavior could be
      established except in lovebirds (Agapornis species). Further research is needed
      to better understand the effect of nutritional and hormonal factors on
      butyrylcholinesterase concentrations in psittacine birds and its possible effect
      on bird cognition.

PMID- 24881149
TI  - Hematologic parameters and hemoparasites of nonmigratory Canada geese (Branta
      canadensis) from Greensboro, North Carolina, USA.
AB  - Large flocks of wild, nonmigratory Canada geese (Branta canadensis) have
      established permanent residence throughout the eastern United States and have
      become a public concern. Few studies have assessed the hematologic parameters for
      these populations, which could provide useful information for monitoring
      individual and population health of Canada geese. This study measured the
      hematologic parameters and detected the presence of hemoparasites from 146 wild,
      nonmigratory Canada geese in central North Carolina, USA, during their annual
      molt. The age class, sex, and weight of each bird were recorded at capture.
      Values for packed cell volume (PCV), estimated white blood cell count, white
      blood cell differentials, and heterophil: lymphocyte ratios were calculated for
      each bird. Adults and female geese had higher estimated white blood cell counts
      compared with juveniles and males, respectively. The PCV increased with weight
      and age class. Adult geese had higher percentages of heterophils and heterophil:
      lymphocyte ratios, whereas juvenile geese had higher percentages of lymphocytes.
      Relative eosinophil counts in adults increased with decreasing bird weight, and
      relative monocyte counts in juveniles increased with increasing weight. Three
      percent of geese were infected with species of Hemoproteus blood parasites.
      Atypical lymphocyte morphology, including pseudopods, split nuclei, and
      cytoplasmic granules, was observed in 5% of the birds. The hematologic values
      reported for adult and juvenile nonmigratory Canada geese in this study may serve
      as reference intervals for ecological studies and veterinary care of wild and
      captive Canada geese.

PMID- 24881150
TI  - Use of an esophagostomy tube as a method of nutritional management in raptors: a
      case series.
AB  - We determined if esophagostomy tube placement is feasible for nutritional support
      in raptors. The clinical data were reviewed from 18 raptors admitted between 2006
      and 2012, and in which esophagostomy tubes were placed. Indications for tube
      placement, complications associated with its placement and management, duration
      of treatment, and changes in patient body weight were evaluated. The most common
      indication was nutritional and medical support in stressed hospitalized animals,
      and intensive care cases. Complications were regurgitation, unexpected removal,
      and misplacement of the tube. The esophagostomy tube was well tolerated in all
      but 2 cases. A tube was replaced once in 2 patients. Five birds died during the
      treatment course. Mortality was not associated with the placement of the tube.
      Average duration of tube placement was 6.1 +/- 3.7 days. Most birds did not gain
      any weight with use of the feeding tubes. Esophagostomy tubes are well tolerated
      in raptors, but further studies are needed to demonstrate their efficiency.

PMID- 24881151
TI  - Diagnostic imaging of peripheral vestibular disease in a Chinese goose (Anser
      cygnoides).
AB  - A 20-year-old Chinese goose (Anser cygnoides) presented for severe left-sided
      head tilt and circling to the left. Peripheral vestibular disease associated with
      otitis media extending into the left quadrate bone was diagnosed by magnetic
      resonance imaging and computed tomography. Otoscopy confirmed a ruptured tympanic
      membrane, and a brainstem auditory evoked response test confirmed loss of hearing
      in the affected ear. Surgery to remove the caseous material and long-term medical
      therapy improved the bird's head tilt and quality of life. Otitis, hearing loss,
      and vestibular disease are rare in birds but can be managed after appropriate
      investigation. This is the first reported use of multiple advanced diagnostic
      tests and successful treatment of vestibular disease in a goose.

PMID- 24881152
TI  - Medical management of acute ocular hypertension in a western screech owl
      (Megascops kennicottii).
AB  - A wild young adult western screech owl (Megascops kennicottii) of unknown sex was
      presented for evaluation of an abnormal left eye (OS). Ophthalmic examination OS
      revealed raised intraocular pressure (37 mm Hg; reference interval 7-16 mm Hg),
      mydriasis, conjunctival and episcleral hyperemia, shallow anterior chamber due to
      anterior displacement of the lens and iris, rubeosis iridis, and engorgement of
      the pecten. The intraocular pressure in the right eye (OD) was 11 mm Hg.
      Multifocal pale, variably translucent, curvilinear to vermiform opacities were
      observed in the medial and ventral peripheral regions of the retina OD,
      consistent with focal retinitis. Mannitol (0.46 g/kg IV) was administered over 10
      minutes. Forty minutes later, the intraocular pressure was 27 mm Hg OS and 13 mm
      Hg OD. Dorzolamide (one drop OS q12h), diclofenac (one drop OU q8-12h), and
      meloxicam (0.5 mg/kg PO q24h) were administered for 3 days. The intraocular
      pressure OS was within normal limits 1 day (11 mm Hg), 7 days (13 mm Hg), and 4
      weeks (14 mm Hg) after this treatment. Complications arising during
      hospitalization and rehabilitation included superficial corneal ulceration of
      both eyes presumed secondary to trauma on being caught and superficial damage to
      a talon. The owl was released after a period of rehabilitation. Characteristic
      presenting signs as well as response to therapy suggest aqueous misdirection was
      the cause of ocular hypertension in this owl. To our knowledge, this is the first
      report of suspected aqueous misdirection and its medical management in a raptor.

PMID- 24881153
TI  - Mucocele in a spectacled owl (Pusilatrix perspicillata).
AB  - A 6-year-old breeding female spectacled owl (Pusilatrix perspicillata) was
      presented for a soft, fluid-filled, spherical mass under the neck that had been
      increasing in size over the previous 3 days. Results of a fine-needle aspirate of
      the mass showed clear, pale-yellow fluid with a total protein of 12.6 g/L.
      Cytologic examination revealed erythrocytes, moderate numbers of heterophils, and
      numerous foamy mononuclear cells against a mucoid background. Macroscopically,
      the mass appeared to be attached firmly to the esophagus. The mass was excised
      surgically and submitted for histopathologic examination. The lesion comprised a
      circumscribed, fibrous-encapsulated multilocular cyst, lined by plump, goblet
      type, cuboidal epithelial cells lying in abundant mucinous matrix. Findings were
      consistent with a mucocele of the esophageal mucosal gland. Excision was
      considered curative based on follow-up 6 months after initial presentation. To
      our knowledge, this is the first report of this condition in Strigiformes and
      indicates that mucocele should be included in the differential diagnosis of
      cervical masses in birds.

PMID- 24881154
TI  - Osteosarcoma of the tibiotarsus with possible pulmonary metastasis in a ring
      necked dove (Streptopelia risoria).
AB  - An unknown-age, adult female ring-necked dove (Streptopelia risoria) was
      presented with an ulcerated mass on the medial side of the right tibiotarsus.
      Radiographs revealed severe boney lysis with proliferative periosteal reaction.
      Surgical amputation was performed at the level of the mid femur and
      histopathologic examination of the mass identified an osteosarcoma. At the 6
      month recheck, the bird was in good condition with no evidence of tumor regrowth
      or metastasis; however, at 8 months, the dove was found dead. On necropsy, a
      large mass was present in the coelomic cavity invading the left pulmonary
      parenchyma. Histopathologic examination indicated a spindle cell sarcoma.
      Immunohistochemical staining for osteocalcin and osteonectin was performed on the
      confirmed osteosarcoma in the tibiotarsus and the spindle cell sarcoma mass.
      Results indicated positive intracytoplasmic immunoreactivity for osteocalcin and
      osteonectin in the confirmed osteosarcoma neoplasm. Very rare positive
      cytoplasmic immunoreactivity occurred in the spindle cell sarcoma.

PMID- 24881155
TI  - Peripheral nerve sheath tumor in a subadult golden eagle (Aquila chrysaetos).
AB  - A 5-year-old, female golden eagle (Aquila chrysaetos) was admitted with
      tetraplegia that progressed to a nonambulatory, spastic tetraparesis after a few
      days of treatment. Clinical and radiologic examinations, including radiography,
      computed tomography scan, and myelography, were indicative of neoplasia involving
      a spinal nerve root. Postmortem magnetic resonance imaging and necropsy findings
      confirmed the diagnosis of a peripheral nerve sheath neoplasia, not, to our
      knowledge, previously reported in a raptor.

PMID- 24881156
TI  - The veterinary bucket list: what's left to do?

PMID- 24881157
TI  - What is your diagnosis? Ventricular metallic foreign body.

PMID- 24881158
TI  - Delicate considerations and blunt instruments.

PMID- 24881159
TI  - To be or not to be.

PMID- 24881160
TI  - Suicidal behaviour in mood disorders--who, when, and why?
AB  - OBJECTIVE: About one-half to two-thirds of all suicides are by people who suffer
      from mood disorders; preventing suicides among those who suffer from them is thus
      central for suicide prevention. Understanding factors underlying suicide risk is
      necessary for rational preventive decisions. METHOD: The literature on risk
      factors for completed and attempted suicide among subjects with depressive and
      bipolar disorders (BDs) was reviewed. RESULTS: Lifetime risk of completed suicide
      among psychiatric patients with mood disorders is likely between 5% and 6%, with
      BDs, and possibly somewhat higher risk than patients with major depressive
      disorder. Longitudinal and psychological autopsy studies indicate suicidal acts
      usually take place during major depressive episodes (MDEs) or mixed illness
      episodes. Incidence of suicide attempts is about 20- to 40-fold, compared with
      euthymia, during these episodes, and duration of these high-risk states is
      therefore an important determinant of overall risk. Substance use and cluster B
      personality disorders also markedly increase risk of suicidal acts during mood
      episodes. Other major risk factors include hopelessness and presence of impulsive
      aggressive traits. Both childhood adversity and recent adverse life events are
      likely to increase risk of suicide attempts, and suicidal acts are predicted by
      poor perceived social support. Understanding suicidal thinking and decision
      making is necessary for advancing treatment and prevention. CONCLUSION: Among
      subjects with mood disorders, suicidal acts usually occur during MDEs or mixed
      episodes concurrent with comorbid disorders. Nevertheless, illness factors can
      only in part explain suicidal behaviour. Illness factors, difficulty controlling
      impulsive and aggressive responses, plus predisposing early exposures and life
      situations result in a process of suicidal thinking, planning, and acts.

PMID- 24881162
TI  - Suicide: rationality and responsibility for life.
AB  - OBJECTIVES: Death by suicide is widely held as an undesirable outcome. Most
      Western countries place emphasis on patient autonomy, a concept of controversy in
      relation to suicide. This paper explores the tensions between patients' rights
      and many societies' overarching desire to prevent suicide, while clarifying the
      relations between mental disorders, mental capacity, and rational suicide.
      METHODS: A literature search was conducted using search terms of suicide and
      ethics in the PubMed and LexisNexis Academic databases. Article titles and
      abstracts were reviewed and deemed relevant if the paper addressed topics of
      rational suicide, patient autonomy or rights, or responsibility for life. Further
      articles were found from reference lists and by suggestion from preliminary
      reviewers of this paper. RESULTS: Suicidal behaviour in a person cannot be
      reliably predicted, yet various associations and organizations have developed
      standards of care for managing patients exhibiting suicidal behaviour. The
      responsibility for preventing suicide tends to be placed on the treating
      clinician. In cases where a person is capable of making treatment decisions-
      uninfluenced by any mental disorder--there is growing interest in the concept of
      rational suicide. CONCLUSIONS: There is much debate about whether suicide can
      ever be rational. Designating suicide as an undesirable event that should never
      occur raises the debate of who is responsible for one's life and runs the risk of
      erroneously attributing blame for suicide. While upholding patient rights of
      autonomy in psychiatric care is laudable, cases of suicidality warrant a delicate
      consideration of clinical judgment, duty of care, and legal obligations.

PMID- 24881163
TI  - The mistreatment of major depressive disorder.
AB  - OBJECTIVE: To examine the effects of classification on treatment in major
      depressive disorder (MDD). METHOD: This is a narrative review. RESULTS: MDD is a
      highly heterogeneous category, leading to problems in classification and in
      specificity of treatment. Current models classify all depressions within a single
      category. However, the construct of MDD obscures important differences between
      severe disorders that require pharmacotherapy, and mild-to-moderate disorders
      that can respond to psychotherapy or remit spontaneously. Patients with mild-to
      moderate MDD are being treated with routine or overly aggressive pharmacotherapy.
      CONCLUSIONS: The current classification fails to address the heterogeneity of
      depression, leading to mistreatment.

PMID- 24881161
TI  - Preventing suicide among inpatients.
AB  - OBJECTIVE: Inpatient suicide comprises a proportionately small but clinically
      important fraction of suicide. This study is intended as a qualitative analysis
      of the comprehensive English literature, highlighting what is known and what can
      be done to prevent inpatient suicide. METHOD: A systematic search was conducted
      on the Cochrane Library, PubMed, Embase, Web of Knowledge, and a personal
      database for articles on cohort series, preferably controlled, of inpatient
      suicide (not deliberate self-harm or attempted suicide, unless they also dealt
      specifically with suicide data). RESULTS: A qualitative discussion is presented,
      based on the findings of the literature searched. CONCLUSIONS: The bulk of
      inpatient suicides actually occur not on the ward but off premises, when the
      patient was on leave or had absconded. Peaks occur shortly after admission and
      discharge. It is possible to reduce suicide risk on the ward by having a safe
      environment, optimizing patient visibility, supervising patients appropriately,
      careful assessment, awareness of and respect for suicide risk, good teamwork and
      communication, and adequate clinical treatment.

PMID- 24881166
TI  - HPV vaccination uptake lowest in young women at greatest risk.

PMID- 24881164
TI  - Time trends in suicide-related behaviours in girls and boys.
AB  - OBJECTIVE: To examine the incidence and nature of emergency department (ED)
      presentations for nonfatal suicide-related behaviours (SRBs) over time, in boys
      and girls living in Ontario. We hypothesize declining rates (fiscal years [FYs]
      2002/03 to 2006/07) ceased thereafter owing to renewed regulatory warnings
      against prescribing antidepressants and the economic recession. METHOD: We
      graphed and tested differences in ED SRB incidence rates for FYs 2002/03 to
      2010/11. We estimated rate ratios and 95% confidence intervals using negative
      binomial regression controlling for changes in the underlying population (age,
      community size, and neighbourhood income quintile). We examined the nature of the
      incident (index) presentations over time in terms of the method(s) used and
      events occurring before and after the index event. RESULTS: ED SRB incidence
      rates decreased by 30% in boys and girls from FYs 2002/03 to 2006/07, but not
      thereafter. This trend was most evident in girls who self-poisoned and in girls'
      presentations to hospital with mental illness in the preceding year. Within a
      year of the index event, the proportion of girls with a repeat ED SRB
      presentation also declined by about one-third, but beyond FYs 2005/06 to 2009/10.
      However, the proportion admitted subsequent to the index event increased by about
      one-third. In boys, their patterns of presentations to hospital with mental
      illness and SRB repetition over time were similar to girls, but estimated with
      greater variability. CONCLUSIONS: While the decline in ED SRB rates to FY 2006/07
      is encouraging, the lack of decline thereafter and an increase in subsequent
      admissions merits ongoing monitoring and evaluation.

PMID- 24881167
TI  - Optimising the management of early prostate cancer.
AB  - One in eight men in the UK will be diagnosed with prostate cancer during their
      lifetime. The risk of prostate cancer is strongly age-related and is also linked
      with a Western lifestyle. Other risk factors include Afro-Caribbean ethnic origin
      and a positive family history. The more first-degree relatives affected the
      greater the risk of developing the disease. More than 70 familial prostate cancer
      susceptibility genes, including the important breast cancer gene BRCA2, have now
      been identified. A suspicion of a diagnosis of prostate cancer is usually based
      on either induration or nodularity of the prostate on digital rectal examination
      or, more commonly, a rise in serum prostate specific antigen (PSA) level. The
      usual cut-off point for PSA is taken as 4 ng/ml, but in men below 65 a value of
      more than 2.5 ng/ml should raise suspicion. A progressive rise in PSA over time
      may also indicate the possibility of the presence of a cancer within the
      prostate. When prostate cancer is suspected, increasingly urologists are
      requesting multiparametric magnetic resonance imaging of the gland before
      deciding whether or not a biopsy is indicated. The Gleason grading of any cancer
      identified is an important part of the decision-making process concerning the
      need for active treatment, as opposed to surveillance alone. Gleason pattern 6
      cancers are regarded as low risk, Gleason 7 intermediate risk and 8-10 high risk.
      In patients diagnosed with intermediate- or high-risk prostate cancer further
      investigations are required to determine the local extent of the disease and to
      exclude the presence of metastases.

PMID- 24881165
TI  - A narrative review of recent developments in knowledge translation and
      implications for mental health care providers.
AB  - OBJECTIVE: Attention to knowledge translation (KT) has increased in the health
      care field in an effort to improve uptake and implementation of potentially
      beneficial knowledge. We provide an overview of the current state of KT
      literature and discuss the relevance of KT for health care professionals working
      in mental health. METHOD: A systematic search was conducted using MEDLINE,
      PsycINFO, and CINAHL databases to identify review articles published in journals
      from 2007 to 2012. We selected articles on the basis of eligibility criteria and
      then added further articles deemed pertinent to the focus of ourpaper. RESULTS:
      After removing duplicates, we scanned 214 review articles for relevance and,
      subsequently, we added 46 articles identified through hand searches of reference
      lists or from other sources. A total of 61 papers were retained for full review.
      Qualitative synthesis identified 5 main themes: defining KT and development of KT
      science; effective KT strategies; factors influencing the effectiveness of KT; KT
      frameworks and guides; and relevance of KT to health care providers. CONCLUSIONS:
      Despite limitations in existing evidence, the concept and practice of KT holds
      potential value for mental health care providers. Understanding of, and
      familiarity with, effective approaches to KT holds the potential to enhance
      providers' treatment approaches and to promote the use of new knowledge in
      practice to enhance outcomes.

PMID- 24881168
TI  - GPs have key role in managing men with testicular cancer.
AB  - Testicular cancer accounts for 1% of all malignancies in males. However, it is
      the most frequently occurring solid tumour in men between the ages of 15 and 34
      years. Testicular germ cell tumours are classified into two main types: pure
      seminomas and non-seminomas which are also called non-seminomatous germ cell
      tumours (NSGCTs). NSGCTs are more clinically aggressive than seminomas so those
      patients who have both seminoma and non-seminoma components are managed according
      to NSGCT guidelines. Testicular tumours have excellent cure rates, even in those
      with metastases, as they are extremely sensitive to chemotherapy and
      radiotherapy. Early diagnosis is, however, very important as treatment is more
      successful and less intensive, and long-term health consequences can be
      minimised. Treatment options include surgery, chemotherapy, radiotherapy, or a
      combination of the above, depending on the histology, presence of tumour markers
      and radiological staging. In most patients, there is recovery of spermatogenesis
      two years after completion of chemotherapy but in all patients, sperm banking
      should be offered before chemotherapy. The risk of developing a secondary
      malignancy is increased in patients treated for testicular cancer. Men who have
      been treated with infradiaphragmatic radiotherapy or chemotherapy also have an
      increased incidence of cardiovascular disease and metabolic syndrome. Patients
      should be screened for cardiovascular risk factors, given healthy lifestyle
      advice and advised not to smoke.

PMID- 24881169
TI  - Self-management pivotal in osteoarthritis.
AB  - Osteoarthritis is not caused by ageing per se, although prevalence does increase
      with age, and does not necessarily deteriorate over time. However, with the
      ageing population the incidence and prevalence of osteoarthritis will continue to
      rise. Osteoarthritis remains a clinical diagnosis and importantly radiographic
      changes and joint symptoms may be poorly correlated. The most commonly affected
      peripheral joints are the knees, hips and small joints of the hand especially the
      distal interphalangeal joints. A diagnosis of osteoarthritis should be reached
      clinically, without the need for investigations, in those older than 45 years,
      with mechanical joint pain, and/or with morning joint-related stiffness lasting
      less than 30 minutes. However, in unclear situations, blood tests and imaging can
      be very helpful to exclude other conditions such as gout, pseudogout, post
      traumatic pain, inflammatory or septic arthritis. All patients with clinical
      osteoarthritis should be advised about activity and exercise irrespective of age,
      comorbidity, pain severity or disability. An effective exercise routine may
      include local muscle strengthening and general aerobic fitness and referral to
      physiotherapy should be considered. A rheumatological opinion should be sought if
      there is doubt regarding the diagnosis or symptoms persist despite treatment.
      NICE recommends yearly follow-up forall osteoarthritis patients who suffer from
      troublesome joint pain, have more than one symptomatic joint, more than one
      comorbidity and/or those patients taking regular medication for the condition.

PMID- 24881170
TI  - Skin infections.

PMID- 24881171
TI  - Therapeutic suggestion. 1914.

PMID- 24881172
TI  - Work in partnership with your patients.

PMID- 24881173
TI  - "Compassion is not missing from the NHS".

PMID- 24881174
TI  - Nurse "stands for NHS" in elections.

PMID- 24881175
TI  - "Staff with the courage to stand up for patients are role models".

PMID- 24881176
TI  - "Hand hygiene is central to tackling antibiotic resistance".

PMID- 24881177
TI  - Supporting women after genital mutilation.
AB  - Female genital mutilation is a common practice in many cultures, and has a range
      of complications. Many women in the UK have undergone the procedure and many
      girls are at risk. This article discusses the types of FGM and its complications,
      and explains how nurses can identify those who have had or are at risk of FGM and
      either offer support or specialist referral.

PMID- 24881178
TI  - Does nurse self-testing affect catheter choice?
AB  - BACKGROUND: Involving patients in decision making about their care requires
      expert knowledge and understanding of patients' perspectives. Knowledge comes
      from several sources and experience; however, the self-testing of products by
      health professionals who teach clean intermittent self-catheterisation (CISC) has
      not been investigated. AIM: This study aimed to assess the impact of self-testing
      on catheter evaluation by continence nurses. METHODS: Sixteen continence nurses
      self-tested two catheters and completed a questionnaire on their opinions about
      the catheter, routine self-testing and whether the study would make them change
      their usual practice. RESULTS: Almost half of the participants found self-testing
      intermittent catheters a useful experience and some of those who did not
      routinely self-test said they would do so in future. CONCLUSION: Self-testing
      intermittent catheters can provide useful knowledge to those who teach CISC.

PMID- 24881179
TI  - Helping schools to manage continence problems.
AB  - The charity organisations Education and Resources for Improving Childhood
      Continence and PromoCon regularly receive feedback from health professionals,
      children and families suggesting that schools struggle to cope with childhood
      continence problems. This article outlines the responsibilities of schools to
      understand continence problems, implement effective policies and procedures to
      meet children's needs, and recognise those children's rights to be supported in
      achieving continence and independence. It also describes the development of a
      toolkit called The Right to Go.

PMID- 24881180
TI  - Childhood eczema treatment: the barriers.
AB  - Childhood eczema has a significant impact on the quality of life of children and
      their families, yet the main cause of treatment failure is parents/carers not
      using prescribed topical treatments. This article reports the results of a study
      that explored carers' experiences of barriers to treatment adherence and how they
      sought to overcome these. We found that regular application of topical treatments
      can be highly challenging, particularly in families where child resistance
      develops. Our findings are considered alongside research into other long-term
      childhood conditions.

PMID- 24881182
TI  - Leadership for better care.

PMID- 24881183
TI  - Are you in the leader zone?

PMID- 24881181
TI  - 60 seconds with Anita Rolfe.

PMID- 24881184
TI  - A question of diversity.

PMID- 24881185
TI  - Girls in gangs 'invisible to the system'.

PMID- 24881186
TI  - Ofsted chief inspector calls for children to start pre-school 'from the age of
      two'.

PMID- 24881187
TI  - Victims of domestic violence failed by police.

PMID- 24881188
TI  - UNICEF UK Baby Friendly Initiative: progress so far.

PMID- 24881189
TI  - Baby Friendly Scotland: a nationwide approach.

PMID- 24881190
TI  - School Nurse 121 campaign.

PMID- 24881191
TI  - Breastfeeding rates in the UK: How can we improve?

PMID- 24881192
TI  - Changing attitudes.

PMID- 24881194
TI  - Family-based childhood obesity interventions in the UK: a systematic review of
      published studies.
AB  - Family-based programmes that emphasise lifestyle and behaviour change using
      psychological principles have been shown to be effective in targeting childhood
      obesity. While there is some evidence that evaluates UK family-based obesity
      interventions at a local level, no review to date has addressed this nationally.
      This review presents the available evidence from UK family-based childhood
      obesity interventions. Ten articles that met the inclusion criteria were included
      for review. The majority of programmes reviewed lasted 12 weeks, with only three
      studies providing follow-up data at 12 months or longer. Change in adiposity may
      be a short-term benefit of participation in a child weight management programme,
      but there is insufficient robust evidence to indicate that this benefit is long
      lasting and many studies were methodologically weak with limited internal
      validity. There is insufficient evidence to suggest how the inclusion of parents
      and the wider family may impact on the effectiveness of UK community based weight
      management programme for children and young people.

PMID- 24881193
TI  - A new model of father support to promote breastfeeding.
AB  - Research shows that fathers can have a considerable influence on a mother's
      decision to initiate and continue with breastfeeding. Despite this, many health
      professionals and broader care services (including maternity services) fail to
      engage meaningfully and systematically with fathers in supporting breastfeeding.
      Although the importance of the father's role in supporting breastfeeding has been
      known for some time, little is known about the nature of this support. No clear
      delineation of which behaviours and attributes constitute father support, or
      differentiate it from other kinds of support, is provided in the current
      literature base. The purpose of this study was to analyse empirically the concept
      of 'father support' in relation to maternity services and broader health
      settings. It aimed to clarify the meaning of 'father support' to enable
      comprehension and application in practice, education and research. As a result,
      we present a new model of father support to promote breastfeeding, and focus
      specifically on some of the practical implications for health practitioners in
      supporting breastfeeding couples.

PMID- 24881195
TI  - Can early breastfeeding support increase the 6-8 week breastfeeding prevalence
      rate?
AB  - Breastfeeding has significant health benefits for mothers and babies and is an
      important strategy to reduce health inequalities (UNICEF, 2010). The Baby
      Friendly Initiative, a strategy to increase breastfeeding rates, has been adopted
      by the trust. In line with the trust's priorities, the health visiting team
      initiated a project to increase the 6-8 breastfeeding prevalence rates.
      Breastfeeding mothers in a defined project area were offered breastfeeding
      support in their homes within the first postnatal week. Although the results
      after six months did demonstrate an overall increase in the 6-8 week prevalence
      rate of 5%, the monthly figures where disappointingly inconsistent and it was
      difficult to attribute the rise to the increased support offered. Nevertheless,
      the feedback from mothers who received support demonstrated that it was valued
      and had a positive impact on their confidence to continue to breastfeed.

PMID- 24881196
TI  - Persistence: the key to success.

PMID- 24881197
TI  - Breastfeeding: new mothers' perspectives.

PMID- 24881198
TI  - A project to improve links between paediatric liaison nurses and school nurse
      teams.

PMID- 24881199
TI  - Public health practice in a new NHS landscape.
AB  - Prediction in relation to professional practice is a risky business and not
      undertaken lightly. However, such is the change in the field of public health
      that some guidance on likely outcomes is worth making. This article has sought to
      identify a number of specific challenges to accepted professional public health
      practice. Public health professionals by their training and skill set are
      expensive when compared to others who could be deployed using a lower level skill
      set. It is suggested that professionals play to their strengths of having a
      greater utility and flexibility. Professionals can do more things to more people
      and to a higher standard. However, it would be advantageous if public health
      professionals did develop their community development skill set, especially if
      they work within deprived areas. This is suggested because of the research that
      is coming to the fore suggesting that the most deprived who have multiple risk
      factors are not benefiting from service provision based on individual need. What
      would reduce their overall risk would be more generic locality work improving
      their health rather than just treating an unhealthy behaviour.

PMID- 24881200
TI  - [Cause of secondary caries and prevention].
AB  - Secondary caries is a disease that occurs on the tooth after the filling has been
      used for a period of time. Secondary caries is also the main reason for the
      replacement of dental restorations. Regardless of the material used for fillings,
      secondary caries cannot be completely avoided. The proportion of secondary caries
      is very high after filling in permanent teeth or primary teeth. Secondary caries
      mainly occurs because of the formation of micro cracks after filling. When the
      micro crack width exceeds 50 microm, saliva will enter the micro cracks between
      the filling and tooth tissue. The cariogenic bacteria in the saliva will grow
      when the environment of micro cracks is appropriate, thereby producing secondary
      caries. The prevention of secondary caries includes micro crack control, fluoride
      use, teeth cleaning, tooth decay and gum disease treatment, and regular checkups.

PMID- 24881201
TI  - [Effects of Porphyromonas gingivalis infection on intercellular adhesion molecule
      1 expression in rat vascular smooth muscle cells].
AB  - OBJECTIVE: To observe the effects of Porphyromonas gingivalis (P. gingivalis)
      ATCC 33277 infection on expression of intercellular adhesion molecule-1 (ICAM-1)
      in rat vascular smooth muscle cells(VSMC). METHODS: An infection model of rat
      VSMC invaded by P. gingivalis was established in vitro. The mRNA of ICAM-1 was
      measured through reverse transcription-polymerase chain reaction (RT-PCR).
      RESULTS: Compared with the control group, an apparent and statistically
      significant increase in expression of ICAM-1 mRNA was observed after 8, 16, and
      24 h in P. gingivals-infected rat VSMC (P<0.05). The expression reached its peak
      at 16 h. Statistically significant differences were observed in the 8 h group and
      in the other two experimental groups (P<0.05). CONCLUSION: Infection of P.
      gingivals in rat VSMC can cause increased expression of ICAM-1, which may have an
      important function in the progression of atherosclerosis.

PMID- 24881202
TI  - [Effect of preparation methods on the metal-porcelain bond strength of Co-Cr
      alloys].
AB  - OBJECTIVE: To compare the shear bond strength(SBS) of cast Co-Cr alloys and
      selective laser melting(SLM) Co-Cr alloys with those of dental porcelain.
      METHODS: A dental porcelain (Vita) was applied on cast and SLM Co-Cr alloy
      specimens (n = 10). SBS test was conducted, and fracture mode analysis was
      determined. Student's t-test by SPSS 13.0 software was employed to analyze the
      data. RESULTS: The SLM Co-Cr alloy specimens had lower SBS values than the cast
      Co-Cr alloy specimens (P > 0.05). The metal-porcelain bond strength value of the
      cast group was (33.11 +/- 4.98) MPa, and that of the SLM group was (30.94 +/-
      5.98) MPa. The specimens in both test groups exhibited mixed failure. CONCLUSION:
      The metal-porcelain system processed by SLM exhibit a bond strength that is
      similar to that of the cast group. This system also display a high precision.

PMID- 24881203
TI  - [Correlation between drinking behavior and polymorphisms of extracellular
      superoxide dismutase, aldehyde dehydrogenase 2 genes, and oral squamous cell
      carcinoma].
AB  - OBJECTIVE: To investigate the correlation between drinking behavior and
      polymorphism combination of extracellular superoxide dismutase (EC-SOD) and
      aldehyde dehydrogenase 2 (ALDH2) genes and oral squamous cell carcinoma. METHODS:
      The genetic polymorphisms of EC-SOD and ALDH2 were analyzed by polymorphism
      polymerase chain reaction technique in peripheral blood leukocytes of 750 oral
      squamous cell carcinoma cases and 750 non-cancer controls. RESULTS: The
      frequencies of EC-SOD (C/G) and ALDH2 variant genotypes were 38.27% and 69.47% in
      oral squamous cell carcinoma cases and 21.07% and 44.40% in healthy controls,
      respectively. Statistical tests showed significant difference in the frequencies
      between the two groups (P < 0.01). The risk of oral squamous cell carcinoma with
      EC-SOD (C/G) was significantly higher than that of controls (OR = 2.32).
      Individuals carrying ALDH2 variant genotypes had high risk of oral squamous cell
      carcinoma (OR = 2.85). Combined analysis of the polymorphisms showed that
      percentages of EC-SOD (C/G)/ALDH2 variant genotypes in oral squamous cell
      carcinoma and control groups were 30.67% and 6.80%, respectively (P < 0.01).
      Individuals carrying EC-SOD (C/G)/ALDH2 variant genotypes had high risk of oral
      squamous cell carcinoma (OR = 8.13). The drinking rate of the case group was
      significantly higher than that in the control group (OR = 2.70). Statistical
      analysis suggested an interaction between drinking and EC-SOD (C/G) and ALDH2
      variant genotypes, which increase risk of oral squamous cell carcinoma (OR =
      25.00). CONCLUSION: EC-SOD (C/G) and ALDH2 variant genotypes and drinking are the
      risk factors in oral squamous cell carcinoma, which could carry out a coordinated
      attack of oral squamous cell carcinoma.

PMID- 24881204
TI  - [Effect of glimepiride on the glucose uptake of rat mandibular osteoblasts in
      hyperglycemia].
AB  - OBJECTIVE: To explore the effect of glimepiride on the glucose uptake as well as
      glucose transporter (GLUT)-1 and GLUT-3 expression levels of rat mandibular
      osteoblasts in hyperglycemia. METHODS: Primary osteoblasts were isolated and
      cultured. Then, the cells were placed in an osteogenic medium containing two
      glucose concentrations (5.5 and 16.5 mmol X L(-1)), with or without glimepiride
      (10 micromol x L(-1)). Glucose uptake was determined by employing 18F
      deoxyglucose (18F-FDG) in the cells, and GLUT-1 and GLUT-3 expression levels were
      evaluated by Western blot analysis. RESULTS: Glucose at 16.5 mmol x L(-1)
      significantly inhibited 18F-FDG uptake and downregulated GLUT-3 protein
      expression in osteoblasts. Hyperglycemia increased GLUT-1 protein expression.
      Glimepiride significantly increased glucose uptake and upregulated GLUT-1 and
      GLUT-3. CONCLUSION: Glimepiride enhance the glucose transporter in rat
      osteoblasts at two different glucose concentrations.

PMID- 24881205
TI  - [Effect of the peri-implantitis on the biological function of osteoblasts
      obtained from the mandibles].
AB  - OBJECTIVE: To study the effect of peri-implantitis inflammatory microenvironment
      on the biological function of jaw bone osteoblasts. METHODS: Primary mandible
      osteoblasts from peri-implantitis and normal tissue were isolated and cultured.
      Third-generation purified osteoblasts were identified and detected. The
      proliferative activity of osteoblasts was evaluated through MTT assay.
      Osteocalcin (OCN), Runx2, and collagen I (Col I) mRNA levels were examined by
      real-time quantitative polymerase chain reaction. OCN protein levels were
      determined by Western blot. RESULTS: : After 4 d of culture, the proliferative
      activity of osteoblasts from peri-implantitis became lower than that of normal
      tissue ( P <0.05). After 7 d of culture, OCN, Runx2, and Col I mRNA expression
      decreased ( P <0.05). The OCN protein levels also decreased ( P <0.05).
      CONCLUSION: Peri-implantitis inflammatory microenvironment can decrease the
      proliferation and differentiation activity of mandible osteoblasts.

PMID- 24881206
TI  - [Influence of parathyroid hormone and estrogen on alveolar bone metabolism of
      castrated female rats].
AB  - OBJECTIVE: To investigate the influence of parathyroid hormone and estrogen on
      alveolar bone metabolism of castrated female rats. METHODS: Sixty-six female
      Wistar rats which were healthy and 4 months old were divided into two groups,
      with group SHAM (n = 18) and group ovariectomy (OVX) (n = 48). After 8 weeks of
      ovariectomy, the osteoporosis model was confirmed by examing 8 ovariectomized and
      sham-operated rats. The rest 10 rats in group SHAM were the control group (group
      A). The rest 40 rats in group OVX were divided into ovariectomized group (group
      B), ovariectomized and treated with estrogen (group C), ovariectomized and
      treated with parathyroid hormone (group D), ovariectomized and treated with
      estrogen and parathyroid hormone (group E) at random with 10 in each group. Group
      A and B injected physiological saline (1 mL x kg(-1)), group C injected estradiol
      benzoate (10 microg x kg(-1)), group D injected parathyroid hormone (20 microg x
      kg(-1)), group E injected parathyroid hormone (20 microg x kg(-1)) and estradiol
      benzoate (10 microg x kg(-1)). The intraperitoneal injection were maken every
      other day to rats in each group, which continued for 8 weeks. The bone mineral
      density (BMD), bone histomorphology and serum Ca, P, alkaline phosphatase (ALP)
      were measured after therapy. RESULTS: After 8 weeks of ovariectomy, the lumbar
      BMD of ovariectomized rats were significantly declined compared with those of the
      sham-operated rats (P < 0.05). Eight weeks later after the drug use, the BMD,
      %Tb.Ar, Tb.Th, Tb.N in group C, D, E were slightly elevated compared to group B,
      especially the group E (P < 0.05). Serum calcium and phosphorus values did not
      change significantly (P > 0.05). ALP values in group B was significantly higher
      than that in group A (P < 0.05). CONCLUSION: Intermittent application of
      parathyroid hormone in small doses can increase alveolar BMD of castration rats
      and improve their bone structure. And it can have synergy effects on the
      treatment of osteoporosis if it is used combining with estrogen.

PMID- 24881207
TI  - [Asymmetric index analysis on the orthodontic-orthognathic treatment of facial
      asymmetry patients in skull positioning posterior-anterior radiographs].
AB  - OBJECTIVE: To analyze the asymmetry of measurements in facial asymmetry patients
      with skull positioning posterior-anterior radiographs after orthodontic
      orthognathic treatment. METHODS: Posterior-anterior cephalometric radiography and
      cephalometric analysis were performed in forty-five patients with different
      degrees of facial asymmetry. A single sample t-test was conducted to compare the
      asymmetry of measurements before treatment and individual normal occlusion. The
      measurement and reference values in facial asymmetry patients who underwent
      orthodontic-orthognathic treatment were summated by analyzing the correlation
      coefficient. The paired t-test was employed to compare the difference between the
      two groups before and after the treatment. RESULTS: Fourteen measurements were
      significantly different before the treatment and individual normal occlusion (P <
      0.05). Me[X] exhibited a higher correlation index of Ag[X] in forty-five cases.
      Twenty-eight patients showed the main asymmetry in the mandibular body, whereas
      fifteen patients in the ramus. Two patients showed the main asymmetry in both
      mandibular body and ramus. Fifteen measurements were significantly different
      before and after the treatment (P < 0.05). CONCLUSION: Facial asymmetry is mainly
      concentrated in one-third of the surface, primarily manifested in the mandibular
      body. Orthodontic-orthognathic treatment is preferred when Ag[X] is greater than
      the minimum reference value of 11.31%, Go[X] is greater than 9.79%, and Me[X] is
      greater than 5.2 mm.

PMID- 24881208
TI  - [Effective evaluation of presurgical nasoalveolar molding devices in the
      treatment of complete unilateral cleft lip and palate patients].
AB  - OBJECTIVE: To evaluate the orthopedic effect of presurgical nasoalveolar molding
      (PNAM) devices on the palatal deformities in unilateral complete cleft lip and
      palate (UCCLP) patients. METHODS: Three groups with 19 patients each were
      studied. All samples in groups A and B were non-syndromic UCCLP children. Group A
      was treated with PNAM prior to operation. Group B was untreated prior to
      operation. Samples in group C were normally developed nose and lip palate infants
      aged three months. The orthotopic palate photos before and after PNAM treatment
      for group A, as well as pre-operative photos of groups B and group C, were taken
      and measured. All statistics were analyzed using SPSS 21.0. RESULTS: PNAM
      treatment significantly increased the AW, AC, and PA of UCCLP patients (P <
      0.05), whereas CPW, CWA, CWAS, CWAH, PMD, and CA significantly decreased (P <
      0.05). However, no significant difference was observed with the cases in group C
      (P < 0.05). The AW, CPW, CA, and PA of the patients in group B significantly
      increased compared with the cases in group A before PNAM treatment (P < 0.05).
      Multivariate analysis of variance indicated that TW had no statistically
      significant difference among the three groups (P > 0.05). CONCLUSION: PNAM
      treatment is a non-surgical early treatment for the effective improvement of
      palatal primary deformities in UCCLP patients.

PMID- 24881209
TI  - [Orthognathic surgery in the treatment of condylar osteochondroma].
AB  - OBJECTIVE: To evaluate the effect of orthognathic surgery in the treatment of
      condylar osteochondroma. METHODS: A total of 12 cases of condylar osteochondroma
      were treated with Le Fort I osteotomy, intraoral vertical ramus osteotomy,
      sagittal split ramus osteotomy and genioplasty. RESULTS: No recurrence of
      condylar osteochondroma was observed in all 12 cases two years after the
      treatments. Facial asymmetry was obviously corrected. CONCLUSION: The
      orthognathic surgery methods are advantageous in improving facial figure without
      scar development in the treatment of condylar osteochondroma.

PMID- 24881210
TI  - [Research on gingival healing situation after stage II surgery of dental
      implantation for periodontitis patients].
AB  - OBJECTIVE: This study aimed to investigate the duration of gingival healing after
      the stage II surgery of dental implantation for periodontitis patients and to
      provide clinical guidelines for implant restoration. METHODS: Twenty-nine
      periodontitis patients who had implantation surgery and achieved osseointegration
      were operated with stage II surgery (a total of 60 pieces of implants). The
      height of buccal gingival of each implant was measured twice after the stage II
      surgery. All implants were measured at the lowest point ofbuccal gingival after
      one week. The implants were randomly divided into four groups according to the
      schedule of the next test time: group one at one week from the initial test
      point, group two at two weeks, group three at three weeks, and group four at four
      weeks. Each group includes 15 pieces of implants. The amount of the buccal
      gingival change in each group between the second and first tests was determined,
      and the data were analyzed statistically. RESULTS: The amount of gingival change
      of groups one, two, three, and four was (-0.25 +/- 0.66), (-0.04 +/- 0.52), (
      0.70 +/- 0.77), and (-0.74 +/- 1.09) mm, respectively. No significant difference
      was observed between groups one and two in terms of the amount of gingival
      changes (P > 0.05). However, a significant difference was found between groups
      two and three (P < 0.05), and the amount of gingival recession was 0.66 mm. No
      significant difference was found between groups three and four (P > 0.05), and
      the gingival achieved stability. CONCLUSION: The gingival recession achieves
      stability at the fourth week (after 28 d) after stage II surgery. At this time,
      the implant can be restored, and the abutment can be selected according to the
      amount of gingival change of the periodontitis patient.

PMID- 24881211
TI  - [Effects of different tooth preparations on the fracture behavior of teeth with
      severe wedge-shaped defect restored with post and core crowns].
AB  - OBJECTIVE: This study aimed to investigate the effects of different tooth
      preparations on the fracture strength and pattern of failure of teeth with severe
      wedge-shaped defect restored with post and core crowns. METHODS: According to
      whether the teeth above the wedge-shaped defect was removed (represented by B) or
      not (represented by A), the ferrule next to the wedge-shaped defect was prepared
      (represented by D) or not (represented by C), the cast post-and-core was chosen
      (represented by E) or glass-fiber post and resin core was chosen (represented by
      F). A total of 64 human mandibular premolar teeth were randomly divided into 8
      groups: A1-1 (A + C + E), A1-2 (A + C + F), A2-1 (A + D + E), A2-2 (A + D + F),
      B1-1 (B + C + E), B1-2 (B + C + F), B2-1 (B + D + E), B2-2 (B + D + F), each
      group 8 teeth. All the teeth were prepared and restored accordingly and then
      mounted on an electronic pressure universal testing machine. The maximum fracture
      strength and the patterns of failure were recorded. RESULTS: 1) The fracture
      strength of Group A1-1 > that of Group B1-1, Group A1-2 > Group B1-2, Group B2-1
      > Group B1-1, and Group B2-1 > Group B2-2 with significant differences (P <
      0.05). 2) The patterns of repairable fracture in Group A1-2 and B1-2 were both
      37.5%, and that of the other groups were 0. Furthermore, the difference was
      significant, and Group A1-2 and B1-2 were higher than other groups. CONCLUSION:
      The maintenance of the overhang above the severe wedge-shaped defect aid in the
      improvement of the fracture strength of the tooth restored with post and core
      crown. The ferrule of the wedge-shaped defect is not recommended to be prepared.
      Furthermore, the glass-fiber post and resin core is favorable for the re-repair
      of the teeth than the cast post and core.

PMID- 24881212
TI  - [Effects of inferior alveolar nerve sectioning on the expression of substance P
      and osteoclast formation in the periodontal tissues].
AB  - OBJECTIVE: This study aimed to investigate the expression function of substance P
      and the formation of osteoclasts in the periodontal tissues after the inferior
      alveolar nerve sectioned in rats. METHODS: Thirty Wistar male rats were used in
      the experiment and were divided into six groups (n = 5) randomly: 0 d (normal), 3
      d, 7 d, 14 d, 21 d, and 28 d. The periodontal tissues were removed from the
      denervation of the inferior alveolar nerve in rats. The periodontal tissues were
      checked by paraffin sections through immunohistochemical staining to trace the
      expression of substance P and through tratrate resistant acid phosphatase (TRAP)
      staining to detect the osteoclasts. The average optical density and osteoclast
      were measured, and the obtained data was statistically analyzed. RESULTS: The
      expression level of substance P in the first three days decreased significantly
      after the inferior alveolar nerve was cut. In addition, the lowest expression
      level was measured after 7 d. Normal levels in the periodontal tissue were
      measured after 21 d. In addition, we found that osteoclasts vary proportionally
      with the changes in substance P. CONCLUSION: The changes in substance P is
      positively correlated with the quantity of osteoclasts after the inferior
      alveolar nerve section. Therefore, we deduce that substance P may regulate the
      differentiation of osteoclasts formation, and thereby participate in the
      balancing of aveular bone metabolism.

PMID- 24881213
TI  - [Lactoferrin downregulates the expression of toll like receptor 4 stimulated by
      lipopolysaccharide in human periodontal ligament cells].
AB  - OBJECTIVE: To examine the role of lactoferrin (LF) on Toll like receptor 4 (TLR4)
      stimulated by lipopolysaccharide (LPS) in human periodontal ligament cells
      (hPDLCs). METHODS: Primary hPDLCs were cultured by tissue block enzymolytic
      method. Cells obtained from four passages were identified and used in this
      experiment. Cells without stimulation served as the controls and cells treated
      with LPS (0.1 microg x mL(-1)) comprised the LPS group. The LPS + LF group was
      pretreated with LPS (0.1 microg x mL(-1)) for 2 h, and then treated with LF (10
      microg x mL(-1)). Four hours after LF stimulation, the mRNA expression levels of
      TLR4 were examined by real-time quantitative polymerase chain reaction (RT-PCR).
      The protein expression of TLR4 was observed by cell immunofluorescence staining
      after LF stimulation of 24 hours. RESULTS: TLR4 mRNA expression in the LPS + LF
      group was significantly more decreased than that in the LPS group (P < 0.05), but
      exhibited no difference with that in the control group (P > 0.05). Cell
      immunofluorescence staining showed that the protein expression of TLR4 in the LPS
      + LF group was significantly more decreased than that in the LPS group (P <
      0.05), but exhibited no difference with that in the control group (P > 0.05).
      CONCLUSION: LF can decrease the expression of TLR4 stimulated by LPS in hPDLCs,
      thus presenting potential application for controlling the TLR4 immune pathway of
      periodontitis.

PMID- 24881214
TI  - [Effect of Er:YAG laser on the dynamic changes in subgingival flora in type 2
      diabetic patients with periodontitis].
AB  - OBJECTIVE: To observe the changes in subgingival microflora before and after
      Er:YAG laser treatment on diabetic patients with periodontitis, and to compare
      with the subgingival microflora of chronic periodontitis. METHODS: Subgingival
      plaque of 13 pairs of teeth (26 sites) was selected from type 2 diabetic patients
      at pretreatment, one month post-treatment, and three months post-treatment.
      Subgingival plaque was also obtained from 11 cases of moderate to severe chronic
      periodontitis with similar severity of periodontitis. The DNA of the subgingival
      plaque samples was extracted. Whole bacterial 16S rDNA gene fragments separated
      by denaturing gradient gel electrophoresis. Specific DNA bands were then chosen
      for retrieval and sequencing. RESULTS: The gene sequencing results of the special
      DNA bands of subgingival plaque samples show that the pathogenic bacteria of both
      diabetic periodontitis and simple chronic periodontitis were Prevotella
      intermedia and Tannerella forsythia, respectively. The composition of the
      subgingival microflora before and after laser treatment changed. Some DNA bands,
      including that of Tannerella forsythia, disappeared or weakened one month after
      treatment. A new strip appeared, which belonged to Actinomyces sp. CONCLUSION:
      The profiles of the subgingival microflora changed after treatment, and one month
      was indicated as an important stage. Er:YAG laser may have an important function
      in delaying microflora recolonization.

PMID- 24881215
TI  - [Human buccal mucosa microbiota succession across age].
AB  - OBJECTIVE: This investigation aimed to examine how buccal mucosa microbiome
      succeeds in a healthy population with different ages and dentition stages.
      METHODS: Twenty-five subjects were recruited and subdivided into five groups:
      primary dentition group, mixed dentition group, adolescent group, adult group,
      and elderly group. Individual mucosal microbiota was obtained by gently scraping
      both sides of the buccal mucosa with a cotton swab. Microbial diversity was
      analyzed by polymerase chain reaction-denaturing gradient gel electrophoresis
      (PCR-DGGE). RESULTS: 1) The composition of buccal mucosa microbiota has great
      intra-individual divergence. 2) The average band numbers of the primary dentition
      group, mixed dentition group, adolescent group, adult group, and elderly group
      were 21.2 +/- 4.0, 17.8 +/- 3.9, 15.8 +/- 4.3, 16.8 +/- 3.7, and 22.2 +/- 6.5,
      respectively. No between-group differences was observed (P > 0.05), indicating
      that predominant strains in the oral cavity may be stable throughout an
      individual's lifetime. 3) The Shannon indices of primary dentition group, mixed
      dentition group, adolescent group, adult group, and elderly group were 1.73 +/-
      10.2, 1.43 +/- 0.1, 1.05 +/- 0.2, 1.45 +/- 0.2, and 1.63 +/- 0.3, respectively. A
      significant between-group difference was observed (P = 0.003), indicating that
      the microbial diversity of the buccal mucosa decreases from childhood through
      adolescence, but increases from adult through senescence. 4) The clustering
      analysis showed that most of the samples in the same group clustered together,
      indicating higher intra-group community structure similarity. CONCLUSION:
      Composition of the buccal mucosa microbiota was different among age groups.
      Adolescence may be an essential turning point of microbial ecology succession
      throughout life.

PMID- 24881216
TI  - [Analysis of the oral microbiota in twin children].
AB  - OBJECTIVE: To analyze the differences between the oral microbiota of monozygotic
      and dizygotic twins by polymerase chain reaction-denaturing gradient gel
      electrophoresis (PCR-DGGE). METHODS: A total of 20 pairs of twin children were
      included in this study, in which 10 pairs were monozygotic (MZ) twins, and 10
      pairs were dizygotic (DZ) twins. Of the 20 pairs, 10 pairs of twins had primary
      dentition, and 10 pairs had mixed dentition; 17 children had caries, and 23
      children had no caries. Genomic DNA was extracted from saliva samples. The 16s
      rRNA was amplified and analyzed by PCR-DGGE. The PCR-DGGE band number and Shannon
      index were calculated. RESULTS: Cluster analysis showed high similarity in the
      oral bacterial community seen in co-twins. However, no significant difference was
      seen between MZ and DZ twins. In the primary dentition, the PCR-DGGE band number
      and Shannon index of children with caries (11.00 +/- 1.56, 1.05 +/- 0.36) were
      lower than those of children without caries (14.00 +/- 2.74, 1.44 +/- 0.37) (P <
      0.05). In mixed dentition, the PCR-DGGE band number and Shannon index of children
      with caries (11.88 +/- 4.05, 1.18 +/- 0.36) were lower than those of children
      without caries (14.31 +/- 5.71, 1.28 +/- 0.47), but the differences were not
      statistically significant (P > 0.05). CONCLUSION: Environmental factors may have
      a stronger effect on the constitution of oral microbiota in children compared
      with genetic factors. Children without caries may have a richer microbial
      diversity compared with children with caries.

PMID- 24881217
TI  - [The molecular mechanism between interstitial fluid pressure and malignant
      phenotype of salivary adenoid cystic carcinoma].
AB  - OBJECTIVE: To explore the effects of stress imposed on adenoid cystic carcinoma
      (ACC), therefore to clarify the molecular basis and mechanism of ACC's malignant
      phenotype under the elevated tumor interstitial fluid pressure. METHODS: ACC
      cells were cultured under pressure (103.74 kPa), and were divided into four
      groups (3 h group, 6 h group, 12 h group, 24 h group) according the pressure
      time. Untreated ACC2 was as negative control group, untreated ACCM was as
      positive control group. The level of epidermal growth factor receptor (EGFR) was
      detected by semiquantitative analysis of immunochemistry. Matrix
      metalloproteinase 9 (MMP9) and EGFR mRNA expression were assessed by reverse
      transcriptase polymerase chain reaction. EGFR, phosphorylation epidermal growth
      factor receptor (P-EGFR), MMP9, keratinocyte growth factor (KGF) and
      phosphorylation extracellular signal-regulated kinase (P-ERK) protein expressions
      were assessed by Western blot. RESULTS: As the extension of pressure time, the
      expression of EGFR, P-EGFR, MMP9, KGF, P-ERK in ACC2 gradually increased, which
      were positive correlation with pressure time, and were higher than that of
      negative control group. CONCLUSION: Under the stimulation of pressure, the mRNA
      and protein levels of adhesion molecules and metastatic relative molecules in
      ACC2 were sharply elevated.

PMID- 24881218
TI  - [Suppression of tumor growth induced by human 4-1BBL-B7-H3 gene in reconstructed
      immune function in severe combined immunodeficient mice].
AB  - OBJECTIVE: The non-specific antitumor immunity effect of 4-1BBL-B7-H3 gene was
      investigated by establishing an oral squamous cell carcinoma human peripheral
      blood lymphocyte-severe combined immunodeficient (SCID) mice chimeric model.
      METHODS: Forty mice were randomly divided into five groups. All groups, except
      the non-immune reconstitution group (group D), had reconstructed human partial
      immune system. The control group (group A) was injected with Tca8113 cells. The
      Ad4-1BBL-B7-H3 group (group B) was injected with Tca8113 cells transfected by
      adenovirus containing 4-1BBL-B7-H3 gene. The empty vector group (group C) was
      injected with Tca8113 cells transfected by adenovirus containing an empty vector.
      The non-immune reconstitution group (group D) was injected with Tca8113 cells.
      The non-tumor group (group E) was injected with PBS. The tumor volumes in each
      group were measured weekly. Human IgG in blood was obtained through the tail vein
      and was determined by enzyme-linked immunosorbent assay. Human CD3+ and D56
      lymphocytes were assessed by flow cytometry. Model animals were killed on the
      ninth week. Differences in the expression of the natural killer group 2 member D
      (NKG2D) and toll-like receptor 2 (TLR2) in tumor tissues of each group were
      observed by immunohistochemical method. 4-1BBL-B7-H3 gene expression in mice
      tumor tissues was detected by reverse transcription polymerase chain reaction
      (PCR) and the expressions of major histocompatibility complex 1 class related
      molecule (M1C) A, M1CB, and TLR2 were detected by real-time quantitative PCR.
      RESULTS: The tumor volumes of group B were remarkably lower than those in the
      other groups (P < 0.05). Human IgG and CD3+ and CD56+ lymphocytes were detected
      in the peripheral blood of immune-reconstituted mice. These lymphocytes were
      remarkably higher in group B than those in groups A, C, and E (P < 0.05). Higher
      NKG2D and TLR2 expression were observed in group B tumor than those in the other
      groups. The stable expression of 4-1BBL-B7-H3 gene in group B was proven. The
      expression of M1CA, M1CB, and TLR2 were significantly higher in the group B tumor
      than those in groups A, C, and D (P < 0.05). CONCLUSION: The high 4-1BBL-B7-H3
      gene expression in tumor tissues could successfully induce the proliferation of
      CD3+ and CD56+ lymphocytes. This expression can also directly or indirectly
      activate TLR2 and up-regulate the expression of NKG2D and its ligands (M1CA and
      M1CB), which result in an effective antitumor immune response.

PMID- 24881219
TI  - [3D finite-element study on displacement of craniofacial complex with retractive
      forces parallel to the occlusion plane on the maxilla of rhesus monkeys].
AB  - OBJECTIVE: To construct a 3D finite-element model of the craniofacial complex
      with the original DICOM data of CT and to investigate the preliminary
      biomechanical characteristics with different directions and magnitudes of
      retractive forces to the maxilla of rhesus monkeys. METHODS: A male rhesus monkey
      with mixed dentition was used. Spiral CT was performed to establish a 3D finite
      element model of the craniofacial complex. The ANSYS 12.1 software was used to
      analyze craniofacial complex displacement. RESULTS: Each landmark showed larger
      displacement with increasing force value. The displacement values and force size
      exhibited a linear relationship. In the x-axis direction, all displacements were
      small. In the y-axis direction, all displacements showed significantly higher
      changes with increasing force value displacement. In the z-axis direction, the A
      point and ANS point moved downward, but PNS moved upward. CONCLUSION: Loading
      retractive force resultes in an apparent backward and clockwise rotation on the
      maxilla with no obvious effects on the width of the upper jaw.

PMID- 24881220
TI  - [Ossifying fibromyxoid tumor in the mandible: a case report].
AB  - Ossifying fibromyxoid tumor is an uncommon neoplasm with uncertain histogenesis.
      This tumor is usually characterized by a small, painless mass in the subcutaneous
      tissue or limb muscles. In this case, an ossifying fibromyxoid tumor of the
      mandible was reported, and relevant literature was reviewed.

PMID- 24881221
TI  - [Left lower extremity venous thrombosis after operation of cyst in the jaw: a
      case report].
AB  - Deep vein thrombosis is a common complication after orthopedic, gynecological,
      and obstetric operations. However, instances of this complication after oral and
      maxillofacial surgeries have been rarely reported. We report a case with
      odontogenic keratocyst in the jaw that gained left lower extremity venous
      thrombosis after operation, and discuss the risk factors and prevention of lower
      extremity venous thrombosis through literature review.

PMID- 24881222
TI  - [Current diagnosis and therapy of anterior mandibular fracture associated with
      condyle fractures].
AB  - Anterior mandibular fracture, which includes symphyseal and parasymphyseal
      mandibular fractures, is one of the most common types of fracture in clinical
      work, and is usually associated with condyle fracture. This type of fracture
      predisposes the patients to facial widening, malocclusion, and ankylosis when not
      properly and timely treated because of the influence of its anatomic structure.
      This article reviews the characteristics, complication, diagnosis, and therapy of
      this type of fracture.

PMID- 24881223
TI  - [Exploration of the oral health education experimental teaching for oral health
      education reform].
AB  - OBJECTIVE: This study aimed to improve students' ability in practical and
      theoretical courses of oral health education and to promote students' learning
      interest and initiative. METHODS: Fourth-year students of the oral medical
      profession from 2006 to 2008 at Weifang Medical University were chosen as
      research objects for oral health education to explore the experimental teaching
      reform. The students were divided into test and control groups, with the test
      group using the "speak out" way of teaching and the control group using the
      traditional teaching method. Results of after-class evaluation of the test group,
      as well as final examination and practice examination of the two groups, were
      analyzed and compared. RESULTS: After-class evaluation results of the test group
      showed that the "speak out" teaching method was recognized by the students and
      improved students' ability to understand oral health education. The final
      examination and practice examination results showed that the score of the test
      group was higher than that of the control group (P < 0.01). CONCLUSION: "Speak
      out" teaching methods can improve students' ability for oral health education, in
      accordance with the trend of teaching reform.

PMID- 24881224
TI  - [Do you speak English?].

PMID- 24881225
TI  - [Result of re-engineering health professions education].

PMID- 24881226
TI  - [Result and perspectives on cooperation between health professionals].

PMID- 24881227
TI  - [When will a statute for patient representatives be created?].

PMID- 24881228
TI  - [Toward a new nutrition politic].

PMID- 24881229
TI  - [Prevention of risk of second primary neoplasms].

PMID- 24881230
TI  - [Medication policy in housing for dependent elderly ].

PMID- 24881231
TI  - [First world atlas of non-satisfied needs in palliative care].

PMID- 24881232
TI  - [A guide to prevent cocaine abuse].

PMID- 24881233
TI  - [More temporary breaks from work for families with handicapped children].

PMID- 24881234
TI  - [French are not hostile to competence transfer].

PMID- 24881235
TI  - ["A solidarity-based healthcare system benefits individual health and public
      health].
AB  - In France, the rise in poverty is having direct consequences on the health of the
      population. The difficulties with regard to access to health are growing and
      people are putting of seeking medical help. These problems affect different
      social categories and concern all regions of the country. Interview with Doctor
      Jean-Francois Corty, director of the French missions of Medecins du Monde.

PMID- 24881236
TI  - [Healthcare institutions for the homeless].
AB  - Samusocial is an organisation which provides emergency and longer-term medical
      respite beds in Paris. They offer, for a duration ranging from a few days to a
      few years, shelter for homeless people requiring medical care but which no longer
      merits hospitalisation. The nursing role consists in supporting as part of a
      multi-professional team these people whose self-esteem and body image have been
      damaged, to help them construct their life project.

PMID- 24881238
TI  - [The mission of caregivers in an administrative detention centre].
AB  - Working as a nurse in a medical unit of an administrative detention centre is a
      choice. The work is made all the more complex by the context of confinement, the
      diversity of the languages and cultures and the undetermined duration of the
      detention. It is with a humanitarian approach that the nursing team of the
      Geispolsheim centre in Alsace deals every day with the health problems of
      vulnerable migrants confronted with insecurity and uncertainty.

PMID- 24881237
TI  - [Re-establishing access to care for the most disadvantaged in rural areas].
AB  - Inhabitants of rural areas are not spared deprivation. In May 2013 Medecins du
      Monde created a Health and Coordination Support Network in Auvergne with the aim
      of reintegrating them into the general healthcare system.

PMID- 24881239
TI  - [Health prevention workshops for women in the north of Marseille].
AB  - The team of the health commission of the Bouches-du-Rhone Secours Populaire is
      made up of nurses, midwives, child healthcare nurses and doctors. Either retired
      or still working, all are volunteers and run health education workshops for women
      in the northern districts of Marseille.

PMID- 24881241
TI  - [Intensive care and radio, two universes that feed of each other].
AB  - The discovery of the healthcare environment can be a stupefying and sometimes
      difficult process. It is a setting where life rubs shoulders with death every day
      and where laughter and tears are equally commonplace. Morgan Houguet, a young
      nurse, shares the humanity of his practice in intensive care.

PMID- 24881240
TI  - [Harm reduction program with sex workers].
AB  - In Nantes, the Medecins du Monde bus goes out three nights a week to meet women
      working as prostitutes. The objective is to create a connection, to inform and to
      prevent the risks inherent to their activity. In this article a nurse shares with
      us the experience of her round.

PMID- 24881242
TI  - [Massage and sophrology workshops for haematology professionals].
AB  - In haematology, the caregivers are confronted with the death of patients and the
      distress of their families. It is a working environment in which it is essential
      for the professionals to be taken care of in order to optimise the care provided
      to patients. At Nantes general hospital, massage and sophrology workshops enable
      the caregivers to recharge their batteries.

PMID- 24881243
TI  - [Giving nurses the desire to take up the challenge of TPE].
AB  - Therapeutic patient education is an integral part of care. It aims to enable
      patients to make informed choices for their health and to fulfil their life
      projects. The nurse is a frontline player in this approach. Particularly
      rewarding, this fast-growing educational practice is a militant commitment, as
      two professionals, experienced in TPE, explain.

PMID- 24881244
TI  - [Privacy and dignity in nursing homes].
AB  - The care provided to the residents of the Alzheimer's unit of the Pont-de-Veyle
      nursing home follows four main ethical principles: dignity, autonomy, beneficence
      and non-maleficence. The team demonstrates flexibility with regard to the washing
      and dressing of the residents, meal times and the organisation of activities. It
      does not resort to restraint. The respect of the person's dignity and privacy is
      maintained not only during nursing care but in all other aspects of their life.

PMID- 24881245
TI  - [Improving the management of rare brain cancers with the POLA network].
AB  - The national POLA network is dedicated to the management of certain rare brain
      tumours, mainly anaplastic oligodendrogliomas, anaplastic oligoastrocytomas and
      glioblastomas with oligodendroglioma component. The nursing team and the patient
      are at the heart of the organisation.

PMID- 24881246
TI  - [Resistance from caregivers and doctors to a transfer to palliative care].
AB  - Doctors' and caregivers' knowledge, acquired experience and representation of
      death might favour or delay a patient's transfer to a palliative care unit. The
      mobile palliative care team, witnessing resistance to a transfer, is in a
      position to respond thanks to the multidisciplinary nature of the team and the
      trust established between the different players in the patient's care.

PMID- 24881247
TI  - [The nurse and treatment of bed sores].

PMID- 24881248
TI  - [The caregiver facing fire risk in health institutions].

PMID- 24881249
TI  - Pain management.
AB  - Assessing pain is an important element of nursing skills. Sophie is careful to
      pay attention to evaluating and relieving her patients' pain. Today, she carries
      out the assessment of a new patient, and also sets up a PCA infusion pump for a
      patient in acute pain.

PMID- 24881250
TI  - [Clinical case on nurse-patient relations].

PMID- 24881251
TI  - [Prevention of complications in tracheotomized patients].

PMID- 24881252
TI  - [Treatment of periodontal disease in diabetes mellitus: useful or not?].

PMID- 24881253
TI  - [Unilateral angioedema of the tongue and the floor of the mouth as a side-effect
      of ACE-inhibitors].
AB  - An 80-year-old woman who was medically compromised had recurrent diffuse
      unilateral swelling of the tongue and the floor of the mouth. The clinical
      working diagnosis of angioedema as a result of the use of ACE-inhibitors
      (lisinopril) was made. In consultation with the cardiologist in charge of her
      case and the general practitioner, the ACE-inhibitor was discontinued. The
      patient's complaints subsequently ceased.

PMID- 24881254
TI  - [Websites of dental practices evaluated].
AB  - In 2013, a dental practice without a website is almost unthinkable. Using a
      sample of309 dentists drawn from the list of members of the Dutch Dental
      Association in 2012, a study was carried out to find out whether the dental
      practice of the general dental practitioner had a website. The content of each
      website was subsequently inventoried using a questionnaire. Eighty-nine percent
      of the dental practices had a website. The content of the websites, however,
      varied enormously. An element such as the professional registration number with a
      reference to the professional register were absent in 73% of the websites and the
      date of the most recent update of the website was mentioned only once. The name
      of the dentist, his or her professional qualification and an email address were
      missing on respectively 9%, 20% and 9% of the websites. Contracts of the practice
      with insurance companies were rarely clearly indicated. The websites of many
      practices would benefit considerably from a significant improvement.

PMID- 24881255
TI  - [Wrinkle fillers in cosmetic facial procedures].
AB  - During the last decade cosmeticfacial procedures have become part of the
      professional work of both dentists and maxillofacial surgeons. A shift has taken
      place from invasive surgical treatment towards minimally invasive treatments.
      Besides the use ofbotulinum toxin type A, non-permanent wrinkle fillers can be an
      alternative to invasive surgical treatment. Since botulism was first described in
      the 18th century, the neurotoxin has continued to develop, as a result of which
      Botox, now available in synthetically produced form, can safely be employed in
      healthcare. The frequency with which patients visit dentists and maxillofacial
      surgeons offers the professional group the possibility to inform patients about
      cosmetic facial treatments and to carry them out according to diagnosis.

PMID- 24881256
TI  - [Technical aspects of treatments with single- and multi-unit fixed dental
      prostheses].
AB  - For the manufacture of single- and multi-unit fixed dental prostheses, effective
      communication between dentist and dental technician is required. Mutual insight
      concerning the (im)possibilities of available treatments and technical options is
      prerequisitefor this communication. The manufacture of single- and multi-unit
      fixed dental prostheses involves 4 phases: recording the required detailed
      information on the relevant teeth and the occlusal system, the technical
      adjustments, the technical design and the technical fabrication. These phases can
      be accomplished through an analogue or (semi)digital procedure. Pioneering
      developments are computer aided design and computer aided manufacturing
      (CAD/CAM), and computerised milling machines. Associated with this are 3
      manufacturing methods which can be distinguished: the dental practice method, the
      dental laboratory method and the milling centre method. Materials applied are
      metal alloys and ceramics, while resins are used for provisional and transitional
      constructions. Due to the fact that the choice of material in the analogue
      procedure is limited, CAD/CAM offers more options, the digital procedure is
      expected to gain ground gradually. It is expected that this development will
      provide an impulse to higher quality.

PMID- 24881257
TI  - [Loading and strength of single- and multi-unit fixed dental prostheses 2.
      Strength].
AB  - The ultimate strength of a dental prosthesis is defined as the strongest loading
      force applied to the prosthesis until afracture failure occurs. Important key
      terms are strength, hardness, toughness and fatigue. Relatively prevalent
      complications of single- and multi-unit fixed dental prostheses are porcelain and
      ceramic fractures. Afactor which also plays a role is the functional loading
      force from the entire orofacial system. With respect to the strength of multi
      unit fixed dental prostheses, the length of the arch span between the abutment
      teeth, the pontic with the connectors and the possible cantilevers are the
      critical components. Components of the configuration ofabutment teeth of single-
      and multi-unit fixed dental prostheses which are relevant for its strength are
      the convergence angle and the design of(the area above) the (cervical) outline.
      Finally, the thickness of the porcelain or the ceramic (veneers) ofmetal-ceramic
      and all-ceramic single- and multi-unit fixed dental prostheses is of importance.

PMID- 24881258
TI  - [Genetics and tooth eruption disorders: a future exploration].

PMID- 24881259
TI  - [Question marks about child dentistry education].

PMID- 24881260
TI  - [Lack of retention of the upper denture: is placement of 2 palatal implants the
      solution?].
AB  - A 72-year-old man, edentulous in the maxilla for 20 years, presented himself at
      his dentist in 2006 with complaints concerning retention of his upper denture.
      The placement of implants was only possible if bone augmentation was undertaken;
      this was definitively rejected by the man. As an alternative, Muchor anchors were
      placed, but these did not provide an adequate solution to the retention problem.
      In the end, 2 palatal implants were placed, with magnetic anchoring. One year
      later, the man was very satisfied with this solution.

PMID- 24881261
TI  - [Recognizing and preventing disturbances in eruption].
AB  - Disturbances in eruption and related problems are quite common in permanent
      dentition but rare in deciduous dentition. For the timely recognition of
      disturbances in eruption, knowledge of the normal development of dentition is
      essential. Disturbances in eruption comprise disturbances in which eruption does
      not occur at all, in which it is delayed or incomplete, or in which the normal
      direction of eruption is influenced. If identified early enough, many undesirable
      dental conditions can be avoided or their seriousness can be limited. A possible
      impacting of permanent cuspids, for example, can be avoided by extracting the
      deciduous cuspids at the right moment; in cases of a large overjet or the threat
      of a cover-bite, lip interference can be prevented.

PMID- 24881262
TI  - [Mechanisms of tooth eruption].
AB  - Tooth eruption is of the utmost importance for the normal development of the
      dentition and the face. Since the 1980s, it has been known that the tooth germ
      itself is not essential for facilitating the processes that make tooth eruption
      possible. For that reason, recent research on the regulatory mechanisms of tooth
      eruption has focused mainly on the enamel organ and the dental follicle.
      Different regulatory mechanisms act on the occlusal and the apical sides of an
      erupting tooth. On the occlusal side osteoclast differentiation is stimulated.
      This leads to the development of an eruption canal, a process in which
      macrophages and matrix metalloproteases also play an important role. On the
      apical side the most important factors are the transcription factor RUNX2 and the
      bone morphogenic protein 2. They are responsible for the deposition of trabecular
      bone in that area. Many regulatory mechanisms which are involved in tooth
      eruption are also active in other developmental processes. This explains that
      certain syndromes can also have an effect on the tooth eruption process.

PMID- 24881263
TI  - [Terminology and manifestations of eruption disturbances].
AB  - Eruption disturbances of teeth are not unusual; many variations are encountered
      and eruption disturbances can negatively influence the development of the tooth
      and jaw system. Causes of eruption disturbances can be categorized into general
      and local factors. The clinical spectrum of eruption disturbances involves
      syndromic and non-syndromic problems for both kinds of factors, varying from
      delayed eruption to primary failure of eruption. The following types of eruption
      disturbances should be distinguished: impaction, primary retention, secondary
      retention and primary failure of eruption. Early detection of eruption
      disturbances and timely and appropriate treatment of the various eruption
      disturbances play an important role in preventing the negative effects of
      eruption disturbances on the development of the dentition and the craniofacial
      skeleton.

PMID- 24881264
TI  - [Primary failure of eruption: diagnostics, treatment, casus and review of
      literature].
AB  - Primary failure of eruption is a rare eruption disorder of above all, the
      permanent second and sometimes the first molars. It is characterized by infra
      occlusion of the molars resulting in a severe lateral open bite. Primary failure
      of eruption is a disorders which affects all molars distal to the most mesial
      involved tooth. Diagnosis is possible both clinically and with radiographs. A
      panoramic radiograph combined with clinical findings of impaction or infra
      occlusion can confirm the suspicion of primary failure of eruption. Primary
      failure of eruption cannot be treated as other eruption disturbances are. The
      teeth do not respond to orthodontic force. Exposure of the molar and orthodontic
      traction of a molar affected by primary failure of eruption is discouraged.
      Observation and extraction, in case the primary failure of eruption poses a risk
      to the healthy dentition, are the only two treatment options for young patients.
      Additional treatment of this eruption disorder should be carried out at an adult
      age and consists of prosthetic closure of the open bite.

PMID- 24881265
TI  - [Tooth eruption disturbances and syndromes].
AB  - In the tooth eruption mechanism, various disturbances can appear as a result of
      gene mutations, a consequence of which can be that tooth eruption does not occur.
      There are 5 syndromes which involve the complete failure of several or even all
      teeth to erupt, specifically: cleidocranial dysplasia, Gardner's syndrome,
      osteopetrosis, mucopolysaccharidosis and GAPO syndrome. Some are very rare and
      will seldom be encountered in a dental practice, but they show how vulnerable the
      tooth eruption mechanism is. Dentists are generally the ones who identify a tooth
      eruption problem in a patient. Since syndromes can be associated with other
      disorders, additional investigation by a clinical geneticist is always important
      when a syndrome is suspected.

PMID- 24881266
TI  - Effect of heat stress on physiological parameters and blood composition in Polish
      Merino rams.
AB  - The Merino sheep represents the most prevalent sheep breed in Poland and is one
      of the most genetic-stable sheep races. Therefore, the aim of the study was to
      determine the responses of Polish Merino sheep to three thermal conditions:
      thermoneutral (16.5 degrees C, group I), mild heat stress (30 degrees C, group
      II), and severe heat stress (50 degrees C, group III). During the experiment
      heart rate (HR; beats/min), respiratory rate (RR; breaths/min), rectal
      temperature (RT) and skin temperatures (ST) were measured daily. The ST measured
      at four points of the animal body was mostly statistically different (p < 0.01)
      between the treatment groups. It was found that the highest HR occurred in group
      II (30 degrees C), and that it was higher than in groups I (16.5 degrees C) and
      III (50 degrees C) (p < 0.01 for groups I, III). The RR was different (p < 0.01)
      in all experimental groups (I, II, III) with the highest increase in group II.
      There was also a clear and significant (p < 0.01) increase in RT during the heat
      stress phases. Blood analysis including morphology, biochemistry and hormones
      (adrenaline, noradrenaline, ACTH, and cortisol) was also performed. Significant
      differences in cortisol level in group II (p < 0.01) and group III (p < 0.05)
      were observed. There was an upward trend in adrenaline and ACTH as a result of
      increasing temperature. Differences in noradrenaline levels (p <0.01), with the
      highest level recorded in group III, were also observed. Additionally there was a
      strong upward trend in blood parameters, especially in hormone concentrations
      (cortisol, noradrenaline).

PMID- 24881267
TI  - Erysipelas in a free-range layer flock with conjunctival oedema as an unusual
      clinical sign.
AB  - Erysipelas was diagnosed in a free-range laying flock with a high mortality of up
      to 7% per day and a severe decrease in egg production to 45%. The disease had a
      short course and unusual clinical features for erysipelas, including swollen,
      lacrimating and encrusted eyes. Bacteriologically, trapped poultry red mites and
      affected animals were culture-positive for Erysipelothrix rhusiopathiae. Isolates
      from layers and mites were both serotype 1b. Histopathology revealed disseminated
      intravasal coagulopathy in conjunctival small vessels as the cause of the oedema
      of the eye adnexes. After treatment with penicillin, mortality and egg production
      returned to normal levels. Although erysipelas in laying hens is rarely reported,
      it can develop as an emerging disease in alternative rearing systems and should
      always be considered if mortality increases in an older flock, especially with a
      high infestation of poultry red mites.

PMID- 24881268
TI  - Analysis of heterophil to lymphocyte ratios in laying hens kept in a small group
      housing system.
AB  - The objective of the present investigation was to assess the level of stress
      imposed on two different layer lines kept in a small group housing system
      Eurovent German with two group sizes and three tiers. A total of 615 Lohmann
      Selected Leghorn (LSL) and 633 Lohmann Brown (LB) hens were examined in four
      consecutive trials. Based on differential white blood cell counts, the heterophil
      to lymphocyte ratio (H/L-ratio) was calculated as an indicator of stress. The H/L
      ratios significantly differed among the two layer lines, with 2.5-fold higher H/L
      ratios in LB than in LSL. No significant differences across and within layer
      lines could be found between the different group sizes. A significant 0.7-fold
      decrease of the H/L-ratio could be shown in LSL layers when the space per hen was
      increased from 828 to 920 cm2.

PMID- 24881269
TI  - [Clinical situation, diagnosis and prevention of a Streptococcus suis serotype 7
      problem on a farm].
AB  - In an Austrian piglet producing farm with 1500 sows a high incidence of
      meningitis, arthritis and sudden death was recorded in five to eight week old
      piglets. Overall losses were 1.8%. Streptococcus (S.) suis serotype 7 was
      detected with an intermediate to high specific bacterial load in all samples
      taken from brains and joints of 17 untreated piglets with typical clinical signs.
      All isolates showed an identical spectrum of virulence-associated genes (mrp+,
      epf-, ofs-, sly-) and expressed a relatively small variant of MRP (Muramidase
      Released Protein) called MRPs. A bacterin was produced using four of the S. suis
      serotype 7 isolates. An untreated and non-vaccinated control group A with 957
      piglets, a non-vaccinated but amoxicillin-treated group B with 1012 piglets and
      an untreated group C with 998 piglets, which was vaccinated twice in the first
      and third week of life, were compared. Later, an additional group D with 290
      piglets was vaccinated twice in the fourth and sixth week of life. Amoxicillin
      treatment in group B resulted in the lowest mortality and morbidity rate.
      Furthermore, the incidence of lameness and losses were significantly lower in
      vaccinated pigs compared to the control group. In an ex vivo blood survival
      assay, a strong bactericidal effect of the post immune sera of group D animals
      was found. This is likely due to the presence of specific opsonizing antibodies
      against S. suis elicited through vaccination and associated with the protective
      efficacy of the vaccine.

PMID- 24881270
TI  - Molecular characterization of Fasciola samples, collected from different host
      species coming from the endemic area of Turkey.
AB  - Economical animal breeding programs are important for achieving maximum gain, and
      any factors resulting in economical loss should be minimized or eliminated. An
      organism of concern is the liver fluke, Fasciola hepatica, which causes decreased
      yield and even death in sheep and dairy cattle. In an effort to eliminate or
      minimize the detrimental effect of this parasite in animals, it is important to
      understand the genetic diversity within the liver flukes and the relationship
      between this parasite and the host in the particular geographic area. The aim of
      this study was to explore genetic diversity by analyzing the mitochondrial ND1
      and cyt b genes and Ribosomal ITS1-2 regions. With these analyses, the individual
      differences, the host animal differences and combined effects of these factors on
      genetic relationships have been determined.

PMID- 24881271
TI  - [Metaphylactic antibiotic treatment of footrot in sheep using Florfenicol].
AB  - A case report describes the metaphylactic antibiotic treatment of 520 sheep
      suffering from footrot (lameness prevalence > 60%) in late pregnancy (targeted
      selective treatment). Because of the lack of pharmaceuticals licensed for sheep
      and footrot in Germany in 2009, Florfenicol was used off label. Clinical recovery
      was observed a few days after a one shot application of florfenicol without any
      further treatment. The examination of all feet after weaning revealed no clinical
      symptoms in 96% of the sheep. Complete healing of almost all affected sheep was
      achieved. No transmission of footrot to lambs was noticed. Since the goal of the
      treatment was relief from pain and suffering under the particular conditions of
      late pregnancy and not a clinical study on efficacy no untreated control group
      was established for comparison. The suitability of the method for eliminating
      footrot in sheep flocks during the housing period in winter is discussed.

PMID- 24881272
TI  - Comparative evaluation of serum, FTA filter-dried blood and oral fluid as sample
      material for PRRSV diagnostics by RT-qPCR in a small-scale experimental study.
AB  - Recently, research into alternative sample materials, such as oral fluid or
      filter-dried blood has been intensified, in order to facilitate cost-effective
      and animal-friendly sampling of individuals or groups of pigs for diagnostic
      purposes. The objective of this study was to compare the sensitivity of porcine
      reproductive and respiratory syndrome virus (PRRSV)-RNA detection by reverse
      transcription quantitative real-time PCR (RT-qPCR) in serum, FTA filter-dried
      blood and oral fluid sampled from individual pigs. Ten PRRSV negative pigs were
      injected with an EU-type PRRSV live vaccine. Blood and oral fluid samples were
      taken from each pig before, and 4, 7, 14 and 21 days after vaccination. All
      samples were then analyzed by PRRSV RT-qPCR. In serum, eight often pigs tested RT
      qPCR positive at different time points post infection. Absolute quantification
      showed low serum PRRSV-RNA loads in most samples. In comparison to serum,
      sensitivity of PRRSV-RNA detection was strongly reduced in matched FTA filter
      dried blood and in oral fluid from the same pigs. These results indicate that
      with low PRRSV-RNA loads the diagnostic sensitivity of PRRSV-RNA detection by RT
      qPCR achieved with serum is currently unmatched by either FTA filter-dried blood
      or oral fluid.

PMID- 24881273
TI  - [First detection of psittacid herpesvirus 2 in Congo African grey parrots
      (Psittacus erithacus erithacus) associated with pharyngeal papillomas and cloacal
      inflammation in Germany].
AB  - Congo African Grey Parrots (GP; Psittacus erithacus erithacus) from four
      different avicultures, presented in the Clinic for Exotic Pets, Reptiles and
      Birds, University of Veterinary Medicine Hannover, Foundation, showed choanal
      papillomas or hyperemia of the cloacal mucosa. Histologically, the mucosal
      choanal proliferations were diagnosed as exophytic papillomas and a mild
      hyperplasia of the cloacal mucosa with lympho-histiocytic inflammation with no
      visible inclusion bodies was found. Herpesvirus genome was detected by nested PCR
      in pooled choanal and cloacal swabs from clinically diseased parrots and healthy
      contact animals. Sequencing of parts of the herpesvirus DNA-polymerase gene
      indicated 98-100% homology of the detected herpesviruses with the Psittacid
      Herpesvirus 2 (PsHV-2). In one aviculture with cloacal inflammation
      papillomavirus-DNA was concurrently found to a PsHV-2 infection. In addition to
      the four avicultures with clinical symptoms 25 more flocks of grey parrots, in
      total 57 Congo-GP and 13 Timneh-GP, were examined for a herpesvirus infection. A
      total of six out of 29 studied parrot avicultures were tested positive for PsHV
      2. The detection of this virus also in flocks of GP, which were bred in Europe,
      shows the establishment of this infection in the GP population in captivity. As
      indicated in the literature as well as in our study PsHV-2 could be only detected
      in Congo-GP, independently if they were kept either alone or in mixed avicultures
      with amazon and macaw species. These findings suggest that PsHV-2 is adapted to
      this Psittacus species.

PMID- 24881274
TI  - [Amyloidosis in turkeys (Meleagris gallopavo f. domestica)--a case report].
AB  - High prevalence of leg disorders in fattening meat turkey farm was observed. Four
      birds as well as tracheal and joint swabs were submitted to the Bavarian Health
      and Food Safety Authority in Oberschleissheim and to the Institute of Poultry
      Diseases, Faculty of Veterinary Medicine, Free University of Berlin. At the post
      mortem, all birds showed an inflammation of the hock joints (intertarsal joint).
      The histopatholical investigations revealed a chronic inflammation of the joint
      and amyloid deposits in the joints in two cases as well as in different tissues
      (liver, spleen and kidneys) in another two cases. Using polymerase chain
      reaction, Ornithobacterium rhinotracheale-DNA could be detected in the examined
      tracheal and joint swabs. On the other hand, Mycoplasma gallisepticum- and
      Mycoplasma synoviae-DNA could not be detected. A causal correlation between the
      detected infectious agent and amyloidosis in relation to the leg disorders were
      discussed.

PMID- 24881275
TI  - In vitro cytotoxicity and multiplex PCR detection of virulence factors of
      Yersinia ruckeri isolated from rainbow trout in North West Germany.
AB  - The aim of this study was to investigate differences in presence and expression
      of virulence factors between biotype 1 and 2 strains of 82 Yersinia (Y.) ruckeri
      isolates, collected from North West Germany during the period of 2004-2012, and
      to analyze the cytotoxicity of these strains to different fish cell lines. The
      common virulence factor genes, such as yhlA and yhlB encoding for hemolysin YhlA,
      rucC and rupG encoding for ruckerbactin, yrp1 and yrpDEF for ABC exporter protein
      system, and two flagellar genes, including flgA for flagellar secretion
      chaperones and flhA for flagellar secretion apparatus, were found present in both
      biotype 1 and 2 isolates of Y. ruckeri collected from North West Germany using
      multiplex PCR. mRNA expression of these genes was compared between the two
      biotypes of Y. ruckeri. There was no significant diversity (p > 0.05) in the
      expression of these genes between biotype 1 and 2 strains. 27 Y. ruckeri isolates
      from different typing groups were analysed in cytotoxicity tests to common carp
      brain (CCB), epithelioma papulosum cyprini (EPC), fathead minnow epithelial (FHM)
      and rainbow trout gonad-2 (RTG-2) cells, respectively. In vitro cytotoxicity of
      the isolates to CCB, EPC and FHM was higher than that to RTG-2 (p < 0.05). At 15
      degrees C the maximum cytotoxicity to FHM and EPC was higher in non-motile
      strains than in motile stains after an incubation of 24 h (p < 0.05), however,
      after 48 h, there was no significant difference (p > 0.05) of cytotoxicity
      between those two biotypes. Our results suggest that biotype 2 strains from North
      West Germany are homogenous with biotype 1 strains on the basis of genetic
      virulence factor genes. At lower temperature non-motile Y. ruckeri isolates were
      found more active than motile strains, which could explain why in winter non
      motile strains were found more often responsible for ERM outbreaks than motile
      strains.

PMID- 24881276
TI  - Felid herpesvirus 1 (FHV 1) carriers among urban breeding facilities in Wroclaw
      (Poland).
AB  - The prevalence of Felid herpesvirus 1 (FHV 1) carriers among closed, one-cat
      breeding facilities in the urban environment of Wroclaw city between 2011-2013
      was investigated. A probe-based real-time PCR was used to detect FHV 1 DNA in
      conjunctival swab extracts. Of the 67 breeding cats investigated 14 animals
      (20.9%) were confirmed to contain FHV 1 specific DNA. The herpesvirus DNA was
      detected in eight cats from the group expressing clinical signs of FHV 1
      infection (n = 28) and in six clinically healthy animals (n = 39). The percentage
      of positive carriers ranged from 12 to 44%, depending on the frequency of
      sampling. The total prevalence in cats at the optimal age for reproduction (2 to
      7 years) was 20%. One-cat breeding facilities of purebred cats in Wroclaw
      (Poland) constitute a significant reservoir of FHV 1 and the number of monitoring
      repeats may influences the success of FHV 1 detection.

PMID- 24881277
TI  - Prevalence of antibodies to Leptospira hardjo in bulk tank milk from unvaccinated
      dairy herds in the south-west region of Poland.
AB  - Bulk tank milk samples were collected from 309 randomly selected dairy cattle
      herds from the south-western region of Poland in 2010-2011. Samples were tested
      for antibodies against Leptospira hardjo using DAS-ELISA. Herd level
      seroprevalence of antibodies against this serovar was low (3.2%). Sample value
      related to positive control value (S/P ratio) results were highest in herds with
      51-100 and 101-500 animals, being 4.6 and 4.1% respectively. The S/P ratio of
      positive samples indicated a low percentage of infected animals in positive
      herds.

PMID- 24881278
TI  - Effects of two dietary vitamin and mineral supplements on the growth and health
      of Hermann's tortoise (Testudo hermanni).
AB  - The aim of the study was to determine the long-term effects of two different
      vitamin and mineral supplements on the growth and health of Hermann's tortoises.
      Twelve one-month-old tortoises were randomly divided into two groups of six
      animals (group A and B). Diets were supplemented on a daily basis with two
      different products ("A": vit. D350 000 IU/kg, 150 g/kg Ca or "B": vit. D3, 2000
      IU/kg, 148 g/kg Ca) for 12 months. Product "B" was richer in most of the
      vitamins. Weight and shell parameters were measured weekly. After one year
      animals in group B had significantly higher final body weights than those in
      group A (186.7 g vs. 131.6 g). The shell of the individuals in group A was firm
      and healthy, while all the tortoises in group B (in different levels) had
      weakened shells. The loss of bone tissue was not so serious to have visual signs
      on x-rays. High amount of vitamins (vitamin E, K, B1, 2, 6, 12, biotin) given for
      safety reasons and relatively low level of vitamin D3 (like in product "B")
      applied on a daily basis seem to be disadvantageous. The moderate metabolic bone
      disease that developed in group B during the experiment could be treated after
      the study by using the supplement "A". The authors recommend such supplements
      which have similar ingredients to product "A" for growing tortoises housed indoor
      with low or without irradiation exposure to UVB.

PMID- 24881279
TI  - Functional exhaustion of T lymphocytes in chronic toxoplasmosis.
AB  - One of the most characteristic features of many intracellular parasite infections
      is their chronicity indicating that the host immune system is not capable of
      eradicating the pathogen. Toxoplasma gondii is the most successful parasite
      worldwide, infecting an extraordinarily broad range of hosts (endothermic animals
      and humans) and almost all cell types. Recent studies have revealed that in late
      chronic toxoplasmosis CD8+ T lymphocytes become progressively exhausted and this
      dysfunction is suggested to be responsible for the reactivation of latent
      infection, which may result in a life-threatening disease in immunocompromised
      individuals (e.g. neurotoxoplasmosis in AIDS patients). The article presents
      selected aspects of a new paradigm--T cell exhaustion phenomenon--a progressive
      dysfunction over time, which makes the host unable to control intracellular
      pathogen infections or tumours.

PMID- 24881280
TI  - Prevalence of fungi in cases of geographical and fissured tongue.
AB  - One of the most common malformations of the tongue is fissured tongue, very
      often, is accompanied by geographic tongue; the etiopathogenesis of them is not
      known. The aim of study was to evaluate the prevalence of fungi in cases of
      fissured and geographic tongue, and to determine their species and susceptibility
      to selected antifungal drugs. The study included 104 patients with fissured
      and/or geographical tongue. To determine fungi present in the tongue, the
      material was collected with a sterile swab for mycological examination. The
      procedure was conducted according to that used at our Department. The in vitro
      susceptibility of the strains to nystatin and miconazole was evaluated. In 45
      (43%) cases fissured tongue, in 28 (27%) geographic tongue, and in 31 (30%) both
      conditions were diagnosed. Mycological examination revealed fungi on the tongue
      in 73 (70%) patients, including 31 patients (69%) with fissured tongue, 19 (68%)
      with geographic tongue, and 23 (74%) with concomitant changes. The most
      frequently detected was Candida albicans (detected in 48-66% of cases); in
      individual cases, other species of Candida species were found. The strains
      demonstrated greater sensitivity to nystatin than to miconazole. An analysis of
      reported symptoms based on the presence or absence of fungi on the tongue
      revealed that idiopathic pain and burning were significantly more frequently
      reported by patients with fungi on the tongue (p = 0.034174). Statistically
      significant differences exist between the presence and absence of fungi with
      regard to the signs, symptoms of changes on the tongue (p = 0.026015). Also,
      statistically significant differences (p = 0.00000) exist regarding the presence
      of fungi with regard to brushing a fissured tongue, or a fissured and geographic
      tongue; fungi are frequently present when brushing is absent. The prevalence of
      fungi is greatest in patients with geographic tongue, especially those who do not
      brush the surface of the tongue.

PMID- 24881282
TI  - Sarcoptic mites (Acari, Sarcoptidae) parasitizing the brown rat Rattus norvegicus
      (Berkenhout, 1769) (Rodentia, Muridae), with a new data for the fauna of Poland.
AB  - One of the least researched groups of parasitic arthropods in the brown rat
      Rattus norvegicus (Berkenhout, 1769) are skin mites from the family of
      Sarcoptidae. Specimens representing two species of sarcoptic mites were found in
      30 examined rats from northern Poland: Notoedres muris Megnin, 1877 and
      Trixacarus diversus Sellnick, 1944. The total prevalence and mean intensity of
      infestation were 13.3% and 3.3, respectively. At the same time, the list of
      sarcoptic mites occurring in Poland was completed with a new genus and new
      species--T. diversus.

PMID- 24881281
TI  - Clinical study of sertaconazole 2% cream vs. hydrocortisone 1% cream in the
      treatment of seborrheic dermatitis.
AB  - Seborrheic dermatitis (SD) is an inflammatory skin disorder affecting the scalp,
      face, and trunk, however, there are controversies surrounding its treatment. The
      aim of the study is to compare the efficacy of sertaconazole 2% cream with
      hydrocortisone 1% cream in the treatment of seborrheic dermatitis. In total, 138
      patients suffering from seborrheic dermatitis were studied. Sixty-nine patients
      received local sertoconazole 2% cream and they were recommended to use the cream
      twice a day and for 4 weeks. To create a control group, 69 patients received
      hydrocortisone 1% cream twice a day for four weeks. At the time of referral, and
      at 2 and 4 weeks after their first visit, the patients were examined by a
      dermatologist to check the improvement of clinical symptoms. The mean age of
      patients was 36.45 +/- 13.23. The highest level of satisfaction (85.1%) was
      observed 28 days after sertaconazole consumption: 76.9% was recorded for the
      hydrocortisone group. No relapse of the disease one month after stopping
      treatment was observed in either the sertaconazole 2% group or the hydrocortisone
      1% group. Sertaconazole 2% cream may be an excellent alternative therapeutic
      modality for treating seborrheic dermatitis.

PMID- 24881283
TI  - The occurrence of Demodex spp. (Acari, Demodecidae) in the bank vole Myodes
      glareolus (Rodentia, Cricetidae) with data on its topographical preferences.
AB  - An examination of 16 bank voles from Poland (Pomerania) revealed the presence of
      two species of the family Demodecidae (Acari, Prostigmata), specific to the host.
      Demodex buccalis Bukva, Vitovec et Vlcek, 1985 was noted only in one bank vole,
      where 18 specimens were found: the prevalence of infestation being 6.3%. D.
      glareoli Hirst, 1919 was observed in 75% of the examined bank voles, in which
      were on average 5.1 specimens. Additionally, mites of the both species exhibited
      topical specificity--representatives of D. buccalis were found in the tissues of
      the tongue and oral cavity of the host, while D. glareoli, being a species
      associated with hair follicles, was noted in skin specimens from different body
      areas, particularly the head area. Infestations with demodecids were not
      accompanied by disease symptoms. D. buccalis and D. glareoli are a new species
      for the fauna of Poland.

PMID- 24881284
TI  - New records of nematodes of passerine migratory birds.
AB  - Parasitological examination of three passerine bird species: the Red-backed
      Shrike Lanius collurio, Eurasian Golden Oriole Oriolus oriolus and Yellow Wagtail
      Motacilla flava, revealed the presence of the nematodes Acuaria subula,
      Diplotriaena ozouxi, Viguiera euryoptera and Microtetrameres inermis. All the
      birds were obtained in the spring (April-May); the nematodes found were mature,
      which indicates infection in the hosts' wintering grounds. The gizzard worm
      Acuaria subula is a new record from Motacilla flava in Europe. Viguiera
      euryoptera and Diplotriaena ozouxi are new to the Polish fauna.

PMID- 24881285
TI  - Preliminary analysis of ectoparasites of the sturgeon Acipenser oxyrinchus
      oxyrinchus (Mitchill, 1815) originating from different water habitats.
AB  - The purpose of this study has been to carry out a preliminary parasitological
      analysis of sturgeon specimens in the context of the presence of external
      parasites, and to determine their possible influence on the health of the fish.
      The examination of external parasites was performed on specimens of A. oxyrinchus
      oxyrinchus captured from an open system pond (the Fish Farm in Kuzniczka, Poland)
      and from the St John River (Canada), in the spring and summer of 2008. Mucus
      collected from the skin surface of the pectoral fin and around the gills of A.
      oxyrinchus oxyrinchus individuals was fixed in 30% ethyl alcohol. The
      preparations were examined under a microscope. In total, 227 specimens of
      parasites were isolated from the skin of A. oxyrinchus oxyrinchus. The parasites
      belonged to three taxa: Protozoa, Monogenea and Crustacea. The degree of
      parasitic infestation by particular parasites in the analyzed samples ranged from
      27.2 to 100%, and the value of the mean infestation varied from 1 to 13.6. Among
      the determined parasites, Trichodina sp. were characterized by the highest
      parasitological parameters. The other determined protozoan, i.e. Apiosoma sp.,
      was found on the skin of half the examined individuals of A. oxyrinchus captured
      from the flow-through pond. Several individuals of the monogenetic fluke
      Gyrodactylus sp. were found on the skin of A. oxyrinchus oxyrinchus originating
      from the pond. Ergasilus sieboldi was identified in the samples obtained from
      both water habitats. Three individuals of the crustacean Argulus coregoni were
      observed on the skin of fish captured in the St John River.

PMID- 24881287
TI  - Celebrating diversity.
AB  - Every hospital has an Eddie Cruz--that high school graduate doing everyman's
      work. Unfortunately, very few hospital C-suites have an Eddie Cruz: a minority.

PMID- 24881286
TI  - Treatment of scabies, permethrin 5% cream vs. crotamiton 10% cream.
AB  - Scabies is one of the three most common skin disorders in children, along with
      tinea and pyoderma. The treatment of choice is still controversial. The aim of
      this study is to compare the efficacy of permethrin 5% cream vs. crotamiton 10%
      cream in the treatment of scabies. In total, 350 patients with scabies were
      enrolled, and randomized into two groups. The first group received permethrin 5%
      cream on two occasions with a one-week interval, while the second group received
      topical crotamiton 10% cream and were told to apply this twice daily for five
      consecutive days. The treatment was evaluated at intervals of 2 and 4 weeks, and
      the treatment was repeated if treatment failure was found at the 2-week follow
      up. Two applications of permethrin 5 % cream provided a cure rate of 70% at the 2
      week follow-up, which increased to 85% at the 4-week follow-up after repeating
      the treatment. Treatment with single applications of crotamiton 10% cream was
      effective in 45% of patients at the 2-week follow-up, which increased to 65% at
      the 4-week follow-up after this treatment was repeated. Two applications of
      permethrin 5% cream was as effective as single applications of crotamiton 10%
      cream at the 2-week follow-up. After repeating the treatment, permethrin 5 %
      cream was superior to crotamiton 10% cream at the 4-week follow up.

PMID- 24881288
TI  - Relationships matter.

PMID- 24881289
TI  - Analyzing ACOs.

PMID- 24881290
TI  - What's the story? Medical schools trying to tell the patient narrative.

PMID- 24881291
TI  - Culture meld. Let's get together, yeah, yeah, yeah.

PMID- 24881292
TI  - Freeze frame. Targeted ads in D.C. subway stations.

PMID- 24881294
TI  - Track-and-alert apps enable true care coordination.

PMID- 24881293
TI  - The hookup. Telemed system speeds stroke care.

PMID- 24881295
TI  - Decisions, decisions.

PMID- 24881296
TI  - Employer mandate. Purchasers holding providers accountable.

PMID- 24881297
TI  - More than a building.
AB  - New payment models and other trends are forcing hospitals to become far more than
      providers of inpatient care. Here are how four organizations are embracing this
      new reality.

PMID- 24881298
TI  - Q&A with Rich Umbdenstock.

PMID- 24881299
TI  - Five new ways to think about the term 'hospital'.

PMID- 24881300
TI  - Speaking the patient's language.
AB  - Former palliative care nurse Sally Okun believes that clinicians are missing a
      huge opportunity to listen to and speak the same language as their patients.

PMID- 24881301
TI  - You got the docs, now keep them! 5 strategies for rural hospitals to help retain
      their hard-won physicians.
AB  - It can be an enormous challenge for rural hospitals to recruit physicians. Here
      are five strategies to make sure that those doctors stay once you've got them on
      board.

PMID- 24881302
TI  - It's a numbers game.
AB  - Absorbing the baby boom generation into Medicare sounds daunting, but health
      care's transformation offers reasons for hope. Part 3 of The Boomer Challenge
      series.

PMID- 24881303
TI  - An unswerving commitment to community service.
AB  - Crozer-Keystone Health System, covering parts of Pennsylvania, Delaware and New
      Jersey, improves lives with an unswerving commitment to community service.

PMID- 24881304
TI  - Physician engagement (getting your docs on board!).
AB  - How can hospitals better engage with docs when so many of them are feeling
      overwhelmed, underappreciated and underpaid?

PMID- 24881305
TI  - CEO on a mission.
AB  - A Detroit hospital leader rallies an entire community around his campaign to
      fight obesity, improve eating habits and promote fitness.

PMID- 24881306
TI  - [Novel class III antiarrhythmic agent niferidile: review of experimental and
      clinical studies].
AB  - This article reviews experimental and clinical studies of a novel antiarrhythmic
      agent niferidile. Niferidile, a class III antiarrhythmic agent, blocks potassium
      outward currents, prolongs repolarization and refractory periods predominantly in
      atria than in ventricles. Intravenous Niferidile was efficient for interruption
      of AV-nodal and orthodromic re-entrant tachycardias with rates of 75% to 80%.
      Niferidile had a conversion rate of up to 87.3% in persistent atrial fibrillation
      and up to 100% in persistent atrial flutter. Proarrhythmic action of niferidil
      administration manifested as nonsustained torsade de pointes and monomorphic
      ventricular tachycardia in 1.2 and 3.7% of cases, respectively. Niferidile can be
      used for pharmacological cardioversion of persistent atrial fibrillation and
      flutter as an alternative to electrical cardioversion.

PMID- 24881307
TI  - [Efficiency and safety of allapinin in short- and long-term treatment of patients
      with normal heart and ventricular premature beats].
AB  - Allapinin, class 1C antiarrhythmic drug, is highly effective in treatment of
      patients with ventricular premature beats (VPB). The purpose of work was
      retrospective assessment of efficacy and safety of allapinin in patients with
      benign ventricular arrhythmias. 73 patients with VPB and no structural heart
      disease were selected from a database. In short course allapininin in dose of 75
      150 mg per os daily decreased the number of VPB for more than 90% in 46,6% of
      patients. In 34,4% cases tolerable drug side effects were observed. Among
      patients with VPB burden of 10% and higher allapinin reduced this quantity below
      the indicated value in 76% of cases with tolerable drug side effects in 38,6% of
      cases. In long treatment study antiarrhythmic effect of allapinin persisted and
      no other side effects of the drug were documented. CONCLUSION: Allapinin is
      highly effective in treatment of patients with VPB without structural heart
      disease.

PMID- 24881308
TI  - [Level of mannose-binding lectin and phagocytic activity of leukocytes in
      patients with acute coronary syndrome].
AB  - Mannose-binding lectin (MBL) is a key component of innate immunity that starts
      one of the ways of complement activation. Factors of neutrophil activation are
      cell factors of innate and acquired immunity. AIM: to study MBL levels and
      factors of neutrophil activation in patients with acute coronary syndrome (ACS).
      METHODS: A total of 45 patients with ST elevation (STE) ACS and non ST-elevation
      (NSTE) ACS were enrolled in the study, 15 persons were age-matched controls.
      RESULTS. Compared with control group MBL level was higher in patients with ACS
      (52.7 vs 127.2 hg/ml, respectively, p = 0.07), and significantly higher in
      patients with NSTE ACS (52.7 vs. 164.7 hg/ml, p = 0.03). There was no difference
      between MBL levels in STE ACS and NSTE ACS patients. Patients with inferior
      myocardial infarction (MI) had significantly higher MBL level than those with
      anterior MI (182.8 -92.7 hg/ml, p = 0.02). Patients with concomitant diabetes had
      statistically higher MBL level than patients without diabetes (225 vs 100 hg/ml,
      OR 2.25, p = 0.03). MBL level was lower in patients with low (<40%) ejection
      fraction - 92.7 vs 148.9 hg/ml in patients with EF > or = 40% (p = 0.19). No
      difference of neutrophil activation factors between ACS patients and controls was
      found (phagocytic activity of neutrophils 74.5 vs 74.3%, phagocytic number 3.34
      vs 4.36, phagocytic reserve 88 vs 85.5 in ACS and control group, respectively).
      CONCLUSION: Elevated innate immunity factor (MBL) level was associated with ACS,
      especially in patients with diabetes mellitus. No association between cell
      immunity factors with ACS was found.

PMID- 24881309
TI  - [Effect of fixed-dose combination of perindopril A/amlodipine on inter visit-to
      visit and inter visit blood pressure and heart rate variability in real clinical
      practice in the Russian observation program KONSTANTA].

PMID- 24881310
TI  - [Economic efficiency of renal denervation in patients with resistant
      hypertension: results of Markov modeling].
AB  - Aim of this study was to evaluate the cost-effectiveness of renal denervation
      (RD) in resistant arterial hypertension (AH) in Russia. Modeling of Markov
      conducted economic impact of RD on the Russian population of patients with
      resistant hypertension in combination with optimal medical therapy (OMT) compared
      with OMT using a model developed by American researchers based on the results of
      international research. The model contains data on Russian mortality, and costs
      of major complications of hypertension. The simulation results showed a
      significant reduction in relative risk reduction of adverse outcomes in patients
      with resistant hypertension for 10 years (risk of stroke is reduced by 30%,
      myocardial infarction - 32%). RD saves 0.9 years of quality-adjusted life (QALY)
      by an average of 1 patient with resistant hypertension. Costs for 1 year stored
      in the application of quality of life amounted to RD 203 791.6 rubles. Which is
      below the 1 gross domestic product and therefore indicates the feasibility of
      this method in Russia.

PMID- 24881311
TI  - [Efficacy and safety of bisoprololal in hypertensive patients with cardiovascular
      disease and chronic obstructive pulmonary disease].
AB  - Efficacy and safety of bisoprolol in hypertensive patients with cardiovascular
      disease and chronic obstructive pulmonary disease. A comparative study on the
      efficacy and safety of bisoprolol and sustained release metoprolol succinate in
      patients with arterial hypertension (AH), cardiovascular disease (CVD) and
      chronic obstructive pulmonary disease (COPD) was conducted. High antihypertensive
      efficacy and good tolerability of bisoprolol and metoprolol succinate sustained
      release was shown in hypertensive patients with CVD and COPD. Bisoprolol versus
      metoprolol succinate sustained release was more effective in reducing the number
      of PVCs in hypertensive patients with CVD and COPD. After 12 weeks of therapy of
      bisoprolol there was a trend to reduce the number of patients with concentric
      left ventricular hypertrophy by 16.6 % (from 83.3% at baseline vs 66.7% after 12
      weeks of treatment, p < 0.1). Despite the fact that the identified changes in
      respiratory function (ERF) in both groups did not reach certainty bisoprolol
      versus metoprolol succinate sustained-release was a lesser extent influenced the
      performance of ERF and more - to reduce dyspnea to the evaluation scales Borg and
      mMRC (delta% = -7.1 in fixed vs delta% = -3.8 in control groups and delta% = -5.6
      vs delta% = 0 respectively) in patients with AH, CVD and COPD.

PMID- 24881312
TI  - [Clinical profile and treatment of left main coronary artery disease in a real
      world practice].
AB  - Aim of this study was to assess clinical profile, treatment and long-term results
      in patients with left main coronary artery disease in a real-world practice. 225
      cases were analyzed. Long-term results were evaluated from 213 (97.7%) patients.
      Median follow-up period was 49 months. Fifty two (23.9%) patients received
      nonsurgical treatment, coronary artery bypass grafting (CABG) was performed in
      106 (48.6%) patients, percutaneous coronary interventions (PCI) in 60 (27.5%)
      patients. Patients of nonsurgical group had more severe clinical profile compared
      with PCI group. There was no differences between nonsurgical and CABG groups as
      well as between CABG and PCI groups in clinical profile. Major adverse cardiac
      and cerebrovascular event rate was higher in nonsurgical group. There was no
      difference between CABG and PCI groups. Survival in CABG and PCI groups was
      higher compared with nonsurgical group. Survival effect of revascularization was
      observed immediately (before 6 months) and continued long-term (more than 60
      months). Revascularization was independent predictor of improved long-term
      survival. After diagnosis of left main coronary artery stenosis PCI was performed
      more quickly than CABG.

PMID- 24881313
TI  - [Factors in the system of prognostication of arterial hypertension].

PMID- 24881314
TI  - [Revascularization or conservative strategy in patients with stable coronary
      heart disease: a contemporary view].
AB  - Choice between revascularization and conservative strategy in patients with
      stable coronary heart disease (CHD) is an important clinical problem, especially
      when the need for revascularization is not urged by severe ischemic symptoms.
      Revascularization aimed to improve prognosis is most justified in patients having
      high risk, based both on results of coronary angiography and functional tests. In
      the opinion of many experts, the high-risk features at stress-test is a key to
      identify patients in whom revascularization is most required among persons with
      high-risk coronary anatomy, as well as to select candidates for invasive
      treatment among patients with more favorable variants of coronary lesions. The
      advantage of revascularization over conservative treatment was demonstrated
      primarily in relation to coronary bypass surgery; however, the prospect of
      replacing surgery by an interventional treatment for prognostic reasons is
      extremely attractive. Although comparison of prognostic efficiency of
      percutaneous coronary intervention (PCI) and coronary bypass surgery (CABG) for
      some categories of patients with stable ischemic heart disease has yielded
      encouraging results, improved survival when using the PCI in direct comparison
      with optimal medical therapy was not convincingly confirmed to date.
      Implementation of PCI to improve prognosis in stable ischemic heart disease is
      still limited by a rather narrow range of indications and the relief of symptoms
      of ischemia remains its main purpose.

PMID- 24881315
TI  - [Visit-to-visit blood pressure variability: clinical and prognostic
      significance].
AB  - The phenomenon of variability of blood pressure (BP) was studied for a long time,
      but recently it has received increased attention, with the focus shifted from
      short-term BP variability, estimated at daily monitoring for clinical blood
      pressure variability from visit to visit, which can be regarded as one of the
      indicators quality control of blood pressure with prolonged treatment. In light
      of the recent years of clinical data from visit to visit BP variability seems a
      promising new target for antihypertensive therapy.

PMID- 24881316
TI  - [Electrocardiogram in acute period of myocardial infarction: from ischemia
      severity and size of myocardial injury to clinical outcome].
AB  - Electrocardiogram (ECG) registered in acute period of myocardial infarction (MI)
      can be used not only for diagnostic purposes, but also for prediction of extent
      of myocardial injury and assessment of prognosis. This review covers assessment
      of acute ischemia in MI using Sclarovsky-Birnbaum classification and Anderson
      Wilkins score, prediction of myocardial injury and necrosis size using changes of
      repolarization and depolarization and relation of these characteristics to
      clinical outcome. The importance of ECG-assessment during reperfusion,
      particularly using continuous ECG-monitoring, is also discussed.

PMID- 24881317
TI  - [Clinical case of malignant pericardial mesothelioma].
AB  - We present a clinical case of pericardial mesothelioma diagnosed in vivo in a 45
      years old patient. Pericardial mesothelioma developed asymptomatically and
      manifested after viral respiratory infection with a clinical picture of exudative
      pericarditis and progressive heart failure. Mesothelioma was eventually diagnosed
      but the patient died. Prevalence of primary pericardial mesothelioma, its risk
      factors, and criteria for diagnosis are also discussed.

PMID- 24881318
TI  - [Trastuzumab-induced cardiomyopathy].
AB  - The treatment of malignant tumors may cause severe adverse reactions including
      cardiovascular problems. The case of a young woman with trastuzumab (Herceptin)
      induced dilatation cardiomyopathy with favorable outcome is presented in the
      article.

PMID- 24881319
TI  - Measuring the burden: alcohol's evolving impact on individuals, families, and
      society.

PMID- 24881320
TI  - Measuring the burden: alcohol's evolving impact.
AB  - Measuring the impact of alcohol consumption on morbidity and mortality depends on
      the accurate measurement of alcohol exposure, risk relationships, and outcomes. A
      variety of complicating factors make it difficult to measure these elements. This
      article reviews these factors and provides an overview of the articles that make
      up this special issue on current research examining alcohol's role in the burden
      of disease. These topics include estimating alcohol consumption as well as
      alcohol-related morbidity and mortality in various demographic groups, and the
      burden of alcohol use disorders.

PMID- 24881321
TI  - Using surveys to calculate disability-adjusted life-year.

PMID- 24881323
TI  - Focus on: the burden of alcohol use--trauma and emergency outcomes.
AB  - Hospital emergency departments (EDs) see many patients with alcohol-related
      injuries and therefore frequently are used to assess the relationship between
      alcohol consumption and injury risk. These studies typically use either case
      control or case-crossover designs. Case-control studies, which compare injured ED
      patients with either medical ED patients or the general population, found an
      increased risk of injury after alcohol consumption, but differences between the
      case and control subjects partly may account for this effect. Case-crossover
      designs, which avoid this potential confounding factor by using the injured
      patients as their own control subjects, also found elevated rates of injury risk
      after alcohol consumption. However, the degree to which risk is increased can
      vary depending on the study design used. Other factors influencing injury risk
      include concurrent use of other drugs and drinking patterns. Additional studies
      have evaluated cross-country variation in injury risk as well as the risk by type
      (i.e., intentional vs. unintentional) and cause of the injury. Finally, ED
      studies have helped determine the alcohol-attributable fraction of injuries, the
      causal attribution of injuries to drinking, and the impact of others' drinking.
      Although these studies have some limitations, they have provided valuable insight
      into the association between drinking and injury risk.

PMID- 24881322
TI  - Assessing the impact of alcohol use on communities.
AB  - Community indicators are used to assess the impact of alcohol on communities.
      This article reviews the main data sources for community indicators, discusses
      their strengths and limitations, and discusses indicators used in reference to
      four main topics relating to alcohol use and problems at the community level:
      alcohol use, patterns, and problems; alcohol availability; alcohol-related health
      outcomes/trauma; and alcohol-related crime and enforcement. It also reviews the
      challenges associated with collecting community indicator data, along with
      important innovations in the field that have contributed to better knowledge of
      how to collect and analyze community-level data on the impact of alcohol.

PMID- 24881326
TI  - APIS: the NIAAA Alcohol Policy Information System.

PMID- 24881324
TI  - Chronic diseases and conditions related to alcohol use.
AB  - Alcohol consumption is a risk factor for many chronic diseases and conditions.
      The average volume of alcohol consumed, consumption patterns, and quality of the
      alcoholic beverages consumed likely have a causal impact on the mortality and
      morbidity related to chronic diseases and conditions. Twenty-five chronic disease
      and condition codes in the International Classification of Disease (ICD)-10 are
      entirely attributable to alcohol, and alcohol plays a component-risk role in
      certain cancers, other tumors, neuropsychiatric conditions, and numerous
      cardiovascular and digestive diseases. Furthermore, alcohol has both beneficial
      and detrimental impacts on diabetes, ischemic stroke, and ischemic heart disease,
      depending on the overall volume of alcohol consumed, and, in the case of ischemic
      diseases, consumption patterns. However, limitations exist to the methods used to
      calculate the relative risks and alcohol-attributable fractions. Furthermore, new
      studies and confounders may lead to additional diseases being causally linked to
      alcohol consumption, or may disprove the relationship between alcohol consumption
      and certain diseases that currently are considered to be causally linked. These
      limitations do not affect the conclusion that alcohol consumption significantly
      contributes to the burden of chronic diseases and conditions globally, and that
      this burden should be a target for intervention.

PMID- 24881325
TI  - Global alcohol-attributable deaths from cancer, liver cirrhosis, and injury in
      2010.
AB  - Alcohol consumption has long been recognized as a risk factor for mortality. By
      combining data on alcohol per capita consumption, alcohol-drinking status and
      alcohol-drinking patterns, risk relationships, and mortality, the Comparative
      Risk Assessment Study estimated alcohol-attributable mortality for 1990 and 2010.
      Alcohol-attributable cancer, liver cirrhosis, and injury were responsible for the
      majority of the burden of alcohol-attributable mortality in 1990 and 2010. In
      2010, alcohol-attributable cancer, liver cirrhosis, and injury caused 1,500,000
      deaths (319,500 deaths among women and 1,180,500 deaths among men) and 51,898,400
      potential years of life lost (PYLL) (9,214,300 PYLL among women and 42,684,100
      PYLL among men). This represents 2.8 percent (1.3 percent for women and 4.1
      percent for men) of all deaths and 3.0 percent (1.3 percent for women and 4.3
      percent for men) of all PYLL in 2010. The absolute mortality burden of alcohol
      attributable cancer, liver cirrhosis, and injury increased from 1990 to 2010 for
      both genders. In addition, the rates of deaths and PYLL per 100,000 people from
      alcohol-attributable cancer, liver cirrhosis, and injury increased from 1990 to
      2010 (with the exception of liver cirrhosis rates for women). Results of this
      paper indicate that alcohol is a significant and increasing risk factor for the
      global burden of mortality.

PMID- 24881327
TI  - The burden of alcohol use: focus on children and preadolescents.
AB  - The study of alcohol use by children ages 12 and younger has been very limited.
      This article summarizes information from U.S. national and statewide surveys on
      the prevalence of alcohol use among children in grades 6 and lower, data on
      health conditions wholly attributable to alcohol, the prevalence of children's
      treatment admissions for alcohol abuse, and their rates of presentation at
      emergency departments for acute alcohol intoxication. Factors hampering the
      estimation of alcohol burden in this population include the lack of ongoing
      national surveys of alcohol use and problems in children, the hand-me-down nature
      of alcohol assessments in this population, and the lack of studies to establish
      whether there is a causal relationship between childhood-onset drinking and
      morbidity and mortality in adolescence and later in life that would permit
      determination of alcohol-attributable fractions. This article concludes that
      although the alcohol burden in childhood is low, it may be augmented by both
      referred alcohol burden through parental drinking and alcohol abuse and by
      deferred alcohol burden from longer-term consequences of early use.

PMID- 24881328
TI  - Prevalence and predictors of adolescent alcohol use and binge drinking in the
      United States.
AB  - Because alcohol use typically is initiated during adolescence and young adulthood
      and may have long-term consequences, the Monitoring the Future (MTF) study
      annually assesses various measures of alcohol use among 8th-, 10th-, and 12th
      grade students. These analyses have found that although alcohol use among these
      age groups overall has been declining since 1975, levels remain high. Thus, in
      2011 about one-quarter of 8th graders, one-half of 10th graders, and almost two
      thirds of 12th graders reported drinking alcohol in the month preceding the
      interview. Binge drinking (i.e., consumption of five or more drinks in a row) was
      also prevalent. Specific rates of drinking, binge drinking, and getting drunk
      varied among different student subgroups based on gender and race/ethnicity. The
      MTF study has also identified numerous factors that influence the risk of alcohol
      use among adolescents, including parents and peers, school and work, religiosity
      and community attachment, exercise and sports participation, externalizing
      behavior and other drug use, risk taking and sensation seeking, well-being, and
      drinking attitudes and reasons for alcohol use. Drinking during adolescence can
      have long-term effects on a person's life trajectory. Therefore, these findings
      have broad implications for prevention and intervention efforts with this
      population.

PMID- 24881330
TI  - Focus on: women and the costs of alcohol use.
AB  - Although light-to-moderate drinking among women is associated with reduced risks
      of some cardiovascular problems, strokes, and weakening of bones, such levels of
      drinking also are associated with increased risks of breast cancer and liver
      problems, and heavy drinking increases risks of hypertension and bone fractures
      and injuries. Women's heavy-drinking patterns and alcohol use disorders are
      associated with increased likelihood of many psychiatric problems, including
      depression, posttraumatic stress disorder, eating disorders, and suicidality, as
      well as increased risks of intimate partner violence and sexual assault, although
      causality in the associations of drinking with psychiatric disorders and with
      violence remains unclear. It is important for women to be aware of the risks
      associated with alcohol use, especially because gaps between U.S. men's and
      women's drinking may have narrowed. However, analyses of health risks and
      benefits need mprovement to avoid giving women oversimplified advice about
      drinking.

PMID- 24881329
TI  - The burden of alcohol use: excessive alcohol consumption and related consequences
      among college students.
AB  - Research shows that multiple factors influence college drinking, from an
      individual's genetic susceptibility to the positive and negative effects of
      alcohol, alcohol use during high school, campus norms related to drinking,
      expectations regarding the benefits and detrimental effects of drinking,
      penalties for underage drinking, parental attitudes about drinking while at
      college, whether one is member of a Greek organization or involved in athletics,
      and conditions within the larger community that determine how accessible and
      affordable alcohol is. Consequences of college drinking include missed classes
      and lower grades, injuries, sexual assaults, overdoses, memory blackouts, changes
      in brain function, lingering cognitive deficits, and death. This article examines
      recent findings about the causes and consequences of excessive drinking among
      college students relative to their non-college peers and many of the strategies
      used to collect and analyze relevant data, as well as the inherent hurdles and
      limitations of such strategies.

PMID- 24881332
TI  - Gaps in clinical prevention and treatment for alcohol use disorders: costs,
      consequences, and strategies.
AB  - Heavy drinking causes significant morbidity, premature mortality, and other
      social and economic burdens on society, prompting numerous prevention and
      treatment efforts to avoid or ameliorate the prevalence of heavy drinking and its
      consequences. However, the impact on public health of current selective (i.e.,
      clinical) prevention and treatment strategies is unclear. Screening and brief
      counseling for at-risk drinkers in ambulatory primary care has the strongest
      evidence for efficacy, and some evidence indicates this approach is cost
      effective and reduces excess morbidity and dysfunction. Widespread implementation
      of screening and brief counseling of nondependent heavy drinkers outside of the
      medical context has the potential to have a large public health impact. For
      people with functional dependence, no appropriate treatment and prevention
      approaches currently exist, although such strategies might be able to prevent or
      reduce the morbidity and other harmful consequences associated with the condition
      before its eventual natural resolution. For people with alcohol use disorders,
      particularly severe and recurrent dependence, treatment studies have shown
      improvement in the short term. However, there is no compelling evidence that
      treatment of alcohol use disorders has resulted in reductions in overall disease
      burden. More research is needed on ways to address functional alcohol dependence
      as well as severe and recurrent alcohol dependence.

PMID- 24881331
TI  - Focus on: ethnicity and the social and health harms from drinking.
AB  - Alcohol consumption is differentially associated with social and health harms
      across U.S. ethnic groups. Native Americans, Hispanics, and Blacks are
      disadvantaged by alcohol-attributed harms compared with Whites and Asians.
      Ethnicities with higher rates of risky drinking experience higher rates of
      drinking harms. Other factors that could contribute to the different effects of
      alcohol by ethnicity are social disadvantage, acculturation, drink preferences,
      and alcohol metabolism. This article examines the relationship of ethnicity and
      drinking to (1) unintentional injuries, (2) intentional injuries, (3) fetal
      alcohol syndrome (FAS), (4) gastrointestinal diseases, (5) cardiovascular
      diseases, (6) cancers, (7) diabetes, and (8) infectious diseases. Reviewed
      evidence shows that Native Americans have a disproportionate risk for alcohol
      related motor vehicle fatalities, suicides and violence, FAS, and liver disease
      mortality. Hispanics are at increased risk for alcohol-related motor vehicle
      fatalities, suicide, liver disease, and cirrhosis mortality; and Blacks have
      increased risk for alcohol-related relationship violence, FAS, heart disease, and
      some cancers. However, the scientific evidence is incomplete for each of these
      harms. More research is needed on the relationship of alcohol consumption to
      cancers, diabetes, and HIV/AIDS across ethnic groups. Studies also are needed to
      delineate the mechanisms that give rise to and sustain these disparities in order
      to inform prevention strategies.

PMID- 24881333
TI  - The world health organization's global monitoring system on alcohol and health.

PMID- 24881335
TI  - Complex regional pain syndrome type I following trauma: a case-report.
AB  - The case report discussed in this article illustrates the painful endeavor of a
      patient who suffered from severe peripheral neuropathic pain and the to-and-from
      treatment adjustments that are needed before an optimal grade of pain control and
      an acceptable quality of life could be achieved. The next to optimal treatment
      was obtained by meticulously adjusting drugs and combining systemic drugs with
      topical ones. Compounding pharmacists play an important role in offering potent
      topical preparations that give an important analgesic added value to complex
      treatments.

PMID- 24881334
TI  - Measuring the burden--current and future research trends: results from the NIAAA
      Expert Panel on Alcohol and Chronic Disease Epidemiology.
AB  - Alcohol has a significant impact on health and well-being, from the beneficial
      aspects of moderate drinking to the detrimental effects of alcoholism. The broad
      implications of alcohol use on public health have been addressed through a wide
      range of epidemiological and clinical studies, many of which are described in
      this issue of Alcohol Research: Current Reviews. Where chronic disease is
      involved, alcohol use can be a risk factor that not only affects the onset of
      various chronic diseases but also exacerbates the ongoing extent and severity of
      those diseases. Lifestyle choices and genetic influences also contribute to, or
      help to alleviate, that risk.

PMID- 24881337
TI  - Determination of risk for sterile preparations.
AB  - A quick and reliable system is described to quantify risk assessment for
      compounded sterile pharmaceuticals, which are "compounded in anticipation" for
      hospitals and clinics, having shelf lives assessed on documented literature and
      other criteria. These shelf lives are well in excess of the recommendations of
      the United States Pharmacopeia without placing patients at risk due to inadequate
      safety, quality, or efficacy.

PMID- 24881336
TI  - Good enough for America.
AB  - Adulterated and counterfeit drugs were pouring into the U.S. Providing poor
      medicines was a growing business, and the market was growing with the rapid
      expansion of the country itself. There seemed to be little that could be done to
      slow or stop it. The sophistication of the adulterations was superior to
      available tests, standards were lacking, and there were few trained pharmacists
      or physicians who could apply them. There were no laws that would prohibit the
      importation of these products nor limit their sale once ashore. This was the
      situation when a small group of New York pharmacists took it upon themselves to
      convince other health professionals and legislators that there was a problem and
      devised a solution that would establish patient safety as the core value of the
      emerging profession of pharmacy.

PMID- 24881339
TI  - The truth about marketing your compounding pharmacy.

PMID- 24881338
TI  - U.S. Food and Drug Administration requests for input on HR 3204 enactment: the
      Drug Quality and Security Act of 2013.

PMID- 24881340
TI  - Basics of compounding: Tips and hints: powders, capsules, tablets, suppositories,
      and sticks, part 1.
AB  - No matter the profession, professionals should never stop learning. This is
      especially true and important in the profession of compounding pharmacy.
      Compounding pharmacists are continuously faced with the challenge of finding new
      and inventive ways to assist patients with their individual and specific drug
      requirements. As compounding pharmacists learn, be it through formal continuing
      education or experience, they should be willing to share their knowledge with
      other compounders. In our goal of providing compounding pharmacists with
      additional knowledge to improve their skills in the art and practice of
      compounding, this article, which provides tips and hits on compounding with
      powders, capsules, tablets, suppositories, and sticks, represents the first in a
      series of articles to assist compounding pharmacists in the preparation of
      compounded medications.

PMID- 24881341
TI  - Laboratory considerations of United States Pharmacopeia Chapter <71> sterility
      tests and its application to pharmaceutical compounding.
AB  - The purpose of this article is to describe United States Pharmacopeia Chapter
      <71> Sterility Tests from the perspective of Current Good Manufacturing Practices
      in order to aid compounding pharmacists in understanding the details and
      complexities that are required. Compounding pharmacists face a unique challenge
      in the industry today, with their compounding practice and the U.S. Food and Drug
      Administration trying to impose Current Good Manufacturing Practices guidelines.
      Naturally, this becomes a challenge to contract testing laboratories as well, as
      they are caught between the testing for non-Current Good Manufacturing Practices
      compounding standards and Current Good Manufacturing Practices manufacturing. It
      is important that the compounding pharmacist and their partner testing laboratory
      work closely together to ensure appropriate requirements are being met.

PMID- 24881342
TI  - Basics of sterile compounding: bubble point testing.
AB  - Compounding pharmacies that compound sterile preparations must choose sterile
      filters that are approved for human use. They may rely on the filter
      manufacturer's Certificate of Quality to ensure the sterile filter is pyrogen
      free and has been tested for bacterial retention. The Certificate of Quality from
      the filter manufacturer also contains other useful information about the filter
      such as: flow rate and maximum pressure drop, thermal and hydraulic stress, and
      membrane results of the initial integrity test performed on the filter membrane
      with water, if a hydrophilic membrane. This article discusses the integrity test,
      which is often called the water bubble point test.

PMID- 24881343
TI  - The effectiveness of sublingual and topical compounded bioidentical hormone
      replacement therapy in postmenopausal women: an observational cohort study.
AB  - Prior studies demonstrated improved menopausal symptom relief following treatment
      with compounded bioidentical hormone replacement therapy; however, clinical
      effectiveness studies evaluating different routes of bioidentical hormone
      replacement therapy administration are lacking. The objective of this study was
      to determine the effectiveness of sublingual and topical compounded bioidentical
      hormone replacement therapy for the treatment of vasomotor, mood, and other
      quality-of-life symptoms in post-menopausal women. This was a prospective,
      observational cohort study of women > or = 18 years of age who received a
      compounded sublingual or topical bioidentical hormone replacement therapy
      preparation between January 1, 2003 and October 1, 2010 in a community pharmacy.
      Data collection included patient demographics, comorbidities, hormone regimens,
      and therapeutic outcomes. Patients rated their vasomotor, mood, and quality-of
      life symptoms as absent, mild, moderate, or severe at baseline, at one to three
      months follow-up, and three to six months follow-up. Baseline characteristics
      were compared using the chi-square test for categorical variables and the
      Wilcoxon rank sum test for continuous variables. Symptom intensity between
      baseline and follow-up periods were compared using the Wilcoxon signed-rank test.
      A total of 200 patients met study criteria; 160 received topical bioidentical
      hormone replacement therapy, and 40 received sublingual bioidentical hormone
      replacement therapy. Most sublingually-treated patients (70%) received an
      estrogen combination and 100% received progesterone. Nearly half (43%) of the
      topically treated patients received an estrogen combination (43%) and 99%
      received progesterone. The percentage of sublingually treated patients reporting
      "moderate" or "severe" symptoms was significantly reduced at one to three months
      follow-up for the following target symptoms: hot flashes (31%, P = 0.04), night
      sweats (38%, P < 0.01), irritability (36%, P = 0.01), anxiety (42%, P < 0.01),
      emotional lability (38%, P < 0.01), sleep disturbances (35%, P < 0.01), memory
      loss (35%, P = 0.04), fatigue (33%, P = 0.04), and libido (26%, P = 0.03).
      Similar reductions were seen at three to six months follow-up compared to
      baseline. Patients who received topical therapy did not experience significant
      symptom reductions at one to three months follow-up; however, significant symptom
      reduction was seen at three to six months for the following: emotional lability
      (31%, P < 0.01), irritability (29%, P = 0.02), and night sweats (20%, P = 0.04).
      Compounded sublingual bioidentical hormone replacement therapy is effective in
      reducing vasomotor, mood, and quality-of-life symptoms experienced in post
      menopausal women. Topical therapy does not appear to improve symptoms as
      extensively or rapidly as sublingual therapy.

PMID- 24881344
TI  - Long-term stability of morphine hydrochloride in 0.9% NaCl infusion polyolefin
      bags after freeze-thaw treatment and in polypropylene syringes at 5 degrees C + 3
      degrees C.
AB  - The aim of this study was to investigate the long-term stability of morphine
      hydrochloride in 0.9% NaCI infusion polyolefin bags and polypropylene syringes
      after storage at 5 degrees C + 3 degrees C and to evaluate the influence of
      initial freezing and microwave thawing on this stability. Ten polyolefin bags and
      five polypropylene syringes containing 100 mL of 1 mg/mL of morphine
      hydrochloride solution in 0.9% NaCI were prepared under aseptic conditions. Five
      polyolefin bags were frozen at -20 degrees C for 90 days before storage.
      Immediately after the preparation and after thawing, 2 mL of each bag were
      withdrawn for the initial concentration measurements. All polyolefin bags and
      polypropylene syringes were then refrigerated at 5 degrees C + 3 degrees C for 58
      days during which the morphine concentrations were measured periodically by high
      performance liquid chromatography using a reversed-phase column, naloxone as
      internal standard, a mobile phase consisting of 5% acetonitrile and 95% of KH2PO4
      buffer (pH 3.50), and detection with diode array detector at 254 nm. Visual and
      microscopic observations and spectrophotometric and pH measurements were also
      performed. Solutions were considered stable if the concentration remained
      superior to 90% of the initial concentration. The degradation products peaks were
      not quantitatively significant and were resolved from the native drug. Polyolefin
      bag and polypropylene syringe solutions were stable when stored at 5 degrees C +
      3 degrees C during these 58 days. No color change or precipitation in the
      solutions was observed. The physical stability was confirmed by visual,
      microscopic, and spectrophotometric inspection. There was no significant change
      in pH during storage. Freezing and microwave thawing didn't influence the
      infusion stability. Morphine hydrochloride infusions may be prepared in advance
      by centralized intravenous additive service, frozen in polyolefin bags, and
      microwave thawed before storage under refrigeration until 58 days either in
      polyolefin bags or polypropylene syringes. Such treatment could improve safety
      and management.

PMID- 24881345
TI  - E-prescribing errors identified in a compounding pharmacy: a quality-improvement
      project.
AB  - Errors during the prescribing process can cause problems for patients. When the
      pharmacist intercepts a prescribing error, it can cause a delay, as the patient
      may not receive the medication until the problem is resolved. Electronic
      prescriptions are purported to reduce prescribing errors. However, studies have
      shown that electronic prescriptions can be prone to certain types of errors.
      Compounding pharmacies may present an additional obstacle for e-prescribing, as
      the prescribed medications are not commercially available and may not be listed
      in the e-prescribing software. The objectives of this study were to estimate the
      electronic prescription error rate in a compounding pharmacy, determine the most
      common error types, list the most common interventions pharmacists made, and
      estimate how long it took to resolve these errors. The study design was quality
      improvement with descriptive data. During the four weeks of data collection, the
      pharmacists were trained to complete a standardized data collection form when
      they identified an electronic prescription error. Percentages were calculated for
      new prescriptions, electronic prescriptions with errors, error types, and error
      resolution methods. In the four-week period of the study, there were 982 new
      prescriptions, 111 of which were electronic prescriptions. Of those 111
      electronic prescriptions, 70 had errors. The electronic prescriptions error rate
      was 63%. The most common type of error was wrong entry field (70.3%). For this
      project, wrong entry field was defined to mean that the drug name was in the
      wrong field (81%) or that multiple entries were in the wrong field (7%).
      Pharmacists usually used their own judgment to resolve an error (67%). Many e
      prescription errors were identified in this compounding pharmacy. When
      prescription errors happen, workflow and patient care are disrupted. Our goal is
      to discuss these findings with Surescripts and e-prescribing software companies
      to seek systems-based solutions.

PMID- 24881346
TI  - Pharmacy benefit managers and compounding pharmacists: billing for services.

PMID- 24881347
TI  - Growth failure and hormone therapy.
AB  - One of the causes of growth failure is growth hormone deficiency. The outcome of
      growth hormone therapy to treat this depends on a number of multifaceted issues,
      including the child, the family and the choice of medication device. Providing
      support and promoting adherence--key nurse roles--are essential for success

PMID- 24881348
TI  - A strong relationship for a long journey.
AB  - Growth hormone treatment can take several years, which requires a high level of
      commitment from patients and families. Endocrine nurses need to build strong
      relationships with patients and their carers in order to prepare them and provide
      tailored, honest support

PMID- 24881349
TI  - Case study. 1. Play therapy to reduce distress.

PMID- 24881350
TI  - Case study. 2. Empowering patients and caregivers around their condition.

PMID- 24881351
TI  - Case study. 3: Resistance to adherence.

PMID- 24881352
TI  - Case study. 4: When adherence is a struggle.

PMID- 24881353
TI  - Treating Turner syndrome: a patient's perspective.

PMID- 24881354
TI  - [Ginecologia y Obstetricia de Mexico].

PMID- 24881355
TI  - [Prevalence of osteopenia and osteoporosis in postmenopausal women and its
      relation to risk factors].
AB  - BACKGROUND: Degenerative diseases are becoming more frequent in adults due to the
      increase in the average life, among them osteoporosis is with one prevalence
      higher in women mainly due to the lack of estrogen after menopause. OBJECTIVE:
      Estimate the prevalence of osteoporosis and osteopenia by effectuate a bone
      densitometry in postmenopausal women and analyze the possible relationship with
      some recognized risk factors. MATERIAL AND METHODS: Cross-sectional study with
      389 patients analyzing the following variables: age; index of body mass and time
      of treatment with hormone replacement therapy, crossing the information with the
      result of bone densitometry. RESULTS: A prevalence rate similar to that reported
      in our country was obtained. We found that patients with overweight have one
      higher percentage of osteopenia and osteoporosis than normal weight, which is
      contrary to what was reported in literature. Also contrary to expectations,
      untreated patients occupy a higher percentage without bone disorders, while in
      the leading hormone therapy the lesser percentage was for those whit
      osteoporosis. We found no differences in terms of age. CONCLUSIONS: Early
      diagnosis provides an excellent opportunity to address these problems but we must
      not forget that the best treatment is prevention from an early age.

PMID- 24881356
TI  - [Progression of gestational hypertension to preeclampsia].
AB  - BACKGROUND: 15 to 25% of patients with gestational hypertension progress to
      preeclampsia. OBJECTIVE: To determine the number of patients with gestational
      hypertension who developed preeclampsia. MATERIALS AND METHODS: Observational
      prospective comparative and longitudinal study realized between november 2010 to
      december 2012. We included pregnant patients diagnosed with mild gestational
      hypertension who were followed during pregnancy to observe the progression to
      preeclampsia. We compared the clinical features of each group among those who
      developed and not the disease. RESULTS: We included a total of 146 patients, of
      whom 36 (25%, IC 95% 17.7-31.7%) progress to preeclampsia. In this group 3 (8%)
      developed mild preeclampsia and 33 (92%) severe preeclampsia, of which 8 (24%)
      account HELLP syndrome. The remaining 110 patients (75%), did not develop
      preeclampsia. From 12 (8%) patients with gestational age < to 28 weeks, 7 (58%)
      developed preeclampsia, 46 (31%) patients between 28-33 weeks, 12 (26%) evolved
      into preeclampsia, 39 (27%) patients between 34-36 weeks, 11 (28%) progressed to
      preeclampsia and finally 49 (34%) with pregnancy > 37 weeks, 6 (12%) developed to
      preeclampsia. When comparing these groups we found that a lower gestational age
      was more frequent the progression to preeclampsia (p < 0.004). The onset of
      gestational hypertension before 28 weeks was significantly associated with the
      progression of preeclampsia (OR 5.1 IC 95% 1.5-17.2). The weight of infants and
      gestational age was lower in children of women who developed the disease in
      comparison that those who did not (p < 0.001). There were no significance
      differences between both groups in relation with body mass index, maternal age,
      parity and antecedent of preeclampsia. CONCLUSIONS: The progression of
      gestational hypertension into preeclampsia appreciated in one of each four
      patients. The progression of gestational hypertension in preeclampsia was more
      common in preterm pregnancy. Most of the patients developed the severe form of
      the disease.

PMID- 24881357
TI  - [Use of intracranial translucency measurement in first trimester, beyond spina
      bifida].
AB  - BACKGROUND: The intracranial translucency (IT) is described as echolucid space
      located in the fetal central nervous system corresponding to the fourth
      ventricle. Alteration in the first trimester is associated with neural tube
      defects (NTDs). OBJECTIVE: To describe as part of the ultrasonographic assessment
      of the first quarter, the technical and the normal values of intracranial
      translucency, factors that affect its display, variability and reproducibility,
      diagnostic operational characteristics (sensitivity and specificity) and other
      utilities in the prenatal diagnosis. METHODS: We conducted an electronic search
      of the literature registered in: PubMed, Ovid, and ProQuest, between September
      2009 and January 2013. RESULTS: It describes technical and normal values, factors
      affecting measurement, intra and inter-observer variability, regarding the
      screening and diagnosis of NTDs. CONCLUSION: The IT should be included in the
      checklist of valuable structures on 11 to 13 6/7 ultrasound; its alteration
      should be related not just o NTDs but posterior fossa anomalies.

PMID- 24881358
TI  - [Convenience clinic redefine polycystic ovary syndrome (Stein-Leventhal)].
AB  - In 1935 during a medical meeting behalf in New Orleans was presents a study that
      included seven cases of women that suffered menstrual dysfunctions, hirsutism and
      sterility, for laparotomy the description of the ovaries had a pearly white color
      and it was hypertrophic, the cuneiform resection in both ovaries resulted in
      correction of the menstrual dysfunction and two of them got pregnancy later on,
      receiving the name of polycystic ovary syndrome (PCOS). The technological advance
      facilitates the hormonal analyses demonstrating the hyperandrogenism existence
      and the mechanism of the anovulation, the PCOS showed to be heterogeneous, reason
      why it was hindered to define it, this advanced the current trend to question the
      existence of the PCOS and to accept the convenience, either to change the name or
      to redefine it, leaving it as a simple syndrome with several phenotypes. The
      endocrine component includes abnormal secretion of insulin and consequently
      outlying resistance to this hormone, likewise is hyperandrogenism,
      dislipoproteinemia and obesity. The hormonal exams are unnecessary for the
      diagnostic and treatment; it is convenient to demonstrate for sonography the
      ovarian growth. Other dysfunctions like the congenital suprarenal hyperplasia,
      hyperprolactinemia and hypotiroidism should be discarded. The treatment should be
      individualized with relationship to the reason of the consultation and the
      patients age. It has not been demonstrated that the sensibilitizers use to the
      insulin avoids long term cardiovascular illness and diabetes. Therefore, the
      phenotype is heterogeneous with a fickle metabolic component and for it has
      arisen the restlessness of a better definition of the SPO.

PMID- 24881359
TI  - [Gartner's duct cyst. Case report and literature review].
AB  - The Gartner's cyst is a remnant of the Wolffian duct, representing 11% of vaginal
      cysts and is usually small, benign and asymptomatic. We report the case of a
      Gartner's duct cyst whose size and localization mimicking a pelvic organ
      prolapse, disease is one of the differential diagnoses.

PMID- 24881360
TI  - [Systemic inflammatory response syndrome in the obstetric patient. Case report].
AB  - The Systemic Inflammatory Response Syndrome is a rare entity during pregnancy.
      This paper describes the case of a 28 year old with a history of abdominal
      distension. She consulted due to abdominal pain in the right upper quadrant
      abdominal pain, gingival bleeding, epigastric pain, nausea and vomiting.
      Obstetrical ultrasound was performed reporting: pregnancy 22 weeks of gestation,
      with heart rate of 118 beats per minute. The patient was admitted requiring
      attention in intensive care units due to their development body hysterotomy was
      performed live only product obtained 430 g. The postpartum period has elapsed so
      torpid development of septic process, making more bilateral salpingo
      hysterectomy.

PMID- 24881361
TI  - [Genital tuberculosis and pregnancy to term. Case report].
AB  - Tuberculosis continues to be a worldwide public health issue, known as "the great
      pretender" resembling many diseases. Overall 1% of women infected with
      Mycobacterium species develop genital tuberculosis (GT) which is widespread more
      commonly during their fertility age, 20-40 years old. GT is the second most
      common cause of extra pulmonary tuberculosis. One of the clinical manifestations
      in these patients is Infertility; with a poor prognosis of a successful pregnancy
      even with a correct diagnosis, medical and/or surgical treatment. Most
      pregnancies result in ectopic pregnancies or abortions. In low income countries
      GT may account for 5-20% of infertility cases. It was widely believed that
      pregnancy represented a period of risk to women infected with tuberculosis; and
      actually abortion is suggested. We report a case of a 21 year old female patient
      who came to the General Hospital Dr. Miguel Silva in the city of Morelia,
      Michoacan with the diagnosis of late puerperium postpartum complicated with
      retained placental tissue to perform a uterine curettage. The patient had fever
      and anemia for which we had to perform a laparotomy exploration of the doubt of
      uterin perforation; the surgical findings were pathognomonic of GT for which we
      continue to realize Hysterectomy. The macro and microscopically pathologic
      findings consists in GT, confirming the diagnosis with Ziehl-Neelsen acid stain.
      GT findings must always be differentiated from ovarian cancer.

PMID- 24881362
TI  - [The breast. Sensual lady].

PMID- 24881363
TI  - [Two cases of Sheehan's syndrome. 1959].

PMID- 24881364
TI  - [Concentration and community diversity of microbes in bioaerosols in the Qingdao
      coastal region].
AB  - Bioaerosol samples were collected in Qingdao coastal region during July 2009 -
      June 2010 to investigate the concentration and community diversity of microbes in
      bioaerosols. Microbe concentrations (bacteria and fungi) in marine and
      terrestrial bioaerosols were determined and diversity indices including Shannon
      Weiner index, Simpson's index and Pielou index were calculated in this study.
      Monthly average concentrations of terrestrial bacteria, marine bacteria,
      terrestrial fungi and marine fungi were in the ranges of 12-436 CFU x m(-3), 25
      561 CFU x m(-3), 0-817 CFU x m(-3) and 11-1346 CFU x m(-3), respectively. There
      were consistent seasonal variations of these four types of microbe, with higher
      concentrations in spring and summer and lowest during winter, especially in
      February. Compared to terrestrial microbes, marine microbes account for higher
      proportion to the total culturable microbes, with a percentage of 63%. The number
      of microbial species varied from 17 to 102, and was partially correlated with
      microbial concentrations, however, it did not show obvious seasonal variation.
      Based on the analysis of calculated diversity indices, we found that the
      community diversities of four types of microbe were much higher in January,
      November and May than in February. The community diversity varied with the
      season, space and different microbial species, and showed a different seasonal
      variation from the microbial concentration.

PMID- 24881365
TI  - [Carbon source apportionment of PM2.5 in Chongqing based on local carbon
      profiles].
AB  - PM2.5 was sampled from commercial, industrial and residential areas in Chongqing
      urban city from 2nd May to 10th May 2012 in order to find out characteristics and
      sources of carbon in PM2.5. Eight kinds of carbons were analyzed by the TOR
      method. Characteristics of carbon pollution in PM2.5 from three kinds of
      functional areas and six kinds of sources, including coal-combustion, exhausts
      (vehicle, boat and construction machine), biomass burning, cooking smoke, were
      analyzed. Based on carbon source profiles, local indicating components of carbon
      sources in PM2.5 were obtained used the chemical mass balance (CMB) model.
      Contribution rate of different sources to PM2.5 carbon were parsed out by factor
      analysis. The results showed the OC/EC of coal-combustion, vehicle exhausts, boat
      exhausts, construction machine exhausts, biomass burning and cooking smoke were
      6.3, 3.0, 1.9, 1.4, 12.7 and 31.3, respectively. High loads of EC2 and EC3
      indicated diesel vehicle exhaust emissions, high loads of OC2, OC3, OC4 and OPC
      indicated coal-combustion emissions, OC1, OC2, OC3, OC4 and EC1 indicated
      gasoline vehicle exhaust emissions, OC3 indicated cooking emissions, and OPC
      indicated biomass burning emissions. OC/PM2.5, EC/PM2.5, secondary organic carbon
      (SOC)/OC in the commercial area were 17.4%, 6.9% and 40.0%, respectively.
      OC/PM2.5, EC/PM2.5 and SOC/OC in the industrial area were 15.5%, 6.6% and 37.4%,
      respectively. OC/PM2.5, EC/PM2.5 and SOC/OC in the residential area were 14.6%
      5.6% and 42.8%, respectively. In the industrial area, the main sources of carbon
      in PM2.5 were coal combustion, gasoline vehicle exhausts and diesel exhaust. In
      the commercial area, the main sources of carbon were gasoline vehicle exhausts,
      diesel exhausts and cooking. In the residential area, the main sources of carbon
      were gasoline vehicle exhausts, cooking smoke and diesel exhausts.

PMID- 24881366
TI  - [Observation of atmospheric pollutants in the urban area of Beibei District,
      Chongqing].
AB  - To study the characteristics of atmospheric pollutants in the urban area of
      Beibei district of Chongqing, the concentrations of the atmospheric pollutants
      were measured by automatic on-line continuous monitoring equipments from Jan.
      2012 to Feb. 2013. The results showed that the concentrations of the pollutants
      often exceeded the corresponding values of the new National Ambient Air Quality
      Standards (GB 3095-2012) except SO2. Of these pollutants, PM2.5 was the most
      serious in this area. The concentrations of the atmospheric pollutants had
      significant seasonal variation. The concentrations of O3 and O(x) were both the
      highest in summer and the lowest in winter. The average concentrations of O3 were
      (36.1 +/- 19.2), (48.8 +/- 32.6), (29.8 +/- 28.6) and (18.2 +/- 15.8) microg x m(
      3), and the average O(x) concentrations were (77.6 +/- 20.6), (91.3 +/- 37.6),
      (77.5 +/- 30.6) and (69.4 +/- 18.2) microg x m(-3) in spring, summer, autumn and
      winter in 2012, respectively. The concentrations of NO(x) appeared higher in
      winter and lower in summer, the average concentrations of NO, NO2 and NO(x) were
      (11.8 +/- 9.4), (42.3 +/- 13.1) and (54.1 +/- 20.8) microg x m(-3) in spring,
      (8.2 +/- 4.9), (40.5 +/- 9.9) and (48.7 +/- 12.6) microg x m(-3) in summer, (20.7
      +/-17.1), (47.2 +/- 14.1) and (67.9 +/- 25.5) microg x m(-3) in autumn, and (30.4
      +/- 25.1), (51.2 +/- 15.9), (81.6 +/- 37.9) microg x m(-3) in winter. The
      concentrations of SO2 appeared higher in spring and winter, and lower in summer
      and autumn. The concentrations of SO2 were (50.5 +/- 23.3), (26.3 +/- 16.7),
      (38.8 +/- 18.4) and (53.7 +/- 23.4) microg x m(-3) in spring, summer, autumn and
      winter, respectively. The concentrations of PM2.5 appeared higher in winter and
      changed smoothly in other seasons, with the average concentration of (61.4 +/-
      28.5), (68.1 +/- 32.5), (61.9 +/- 27.1) and (89.6 +/- 44.2) microg x m(-3) in
      spring, summer, autumn and winter, respectively. The curves of diurnal variations
      of O3, O(x), NO, NO(x) and SO2 all showed single peak. However, the time of the
      peak values varied for different pollutants, 16:00 for O3 and O(x), and 8:00
      11:00 for NO, NO(x) and SO2. The diurnal variations of NO2 and PM2.5 were similar
      to the two peaks that appeared in the morning and at night, respectively.
      Moreover, the diurnal ranges of O3 and O(x) concentrations were much wider in
      summer, while the wider ranges were observed in winter for NO, NO2, NO(x), SO2
      and PM2.5. There was no difference in the diurnal pattern of NO between weekends
      and weekdays, the concentrations of N2O in weekdays were much higher than those
      on weekends, but with O3 the situation was the opposite. Correlation analysis
      indicated that the O3 concentration was positively correlated with temperature
      and wind speed, while negatively correlated with relative humidity. However, the
      situation of NO(x) was the opposite. PM2.5 concentration was negatively
      correlated with temperature and wind speed, while positively correlated with
      relative humidity. SO2 concentration had different correlations with the
      meteorological parameters in different seasons. In addition, wind direction was
      an important factor affecting the concentrations of the atmospheric pollutants.

PMID- 24881367
TI  - [A floating-dust case study based on the vertical distribution of aerosol optical
      properties].
AB  - The vertical distribution of aerosol optical properties of a typical floating
      dust event on October 19, 2009 in Shanghai was analyzed by using Micro-pulse
      Lidar (MPL) and the CALIPSO satellite. The results showed that the floating-dust
      aerosol mainly existed below 2 km of height. The floating-dust aerosol
      backscatter coefficient ranged from 0 to 0.015 km(-1) x sr(-1), and the MPL
      extinction coefficient ranged from 0 to 0.32 km(-1). The MPL data showed that the
      aerosol extinction coefficient first increased and then decreased during the
      floating-dust event. At the same time, the aerosol layer was constantly lifting.
      The CALIPSO data showed that a large number of small particles were suspended in
      air at a height of below 2 km, while the big particles always stayed near the
      ground (0-0.5 km). At the height of 2-10 km, there was only few aerosols; in the
      range of 4-6 km, there was a mixture of particles with regular and irregular
      shapes. The vertical distribution of CALIPSO 532 nm total attenuated backscatter
      coefficient and MPL normalized relative backscatter signal was basically the
      same, but the extinction coefficient values gained by them were different.
      Observations by CALIPSO and MPL together could be more comprehensive and
      objective for monitoring floating-dust in Shanghai.

PMID- 24881368
TI  - [Analysis and assessment of atmospheric pollution based on accumulation
      characterization of heavy metals in Platanus acerifolia leaves].
AB  - The present work was aimed to evaluate the heavy metal pollution in the
      atmosphere of Huainan City. We measured and clustered the accumulation of six
      heavy metals in Platanus acerifolia leaves in 20 sampling fields with six types
      of environmental conditions, and analyzed the EF value of heavy metal enrichment
      in the leaves. The results showed that the accumulations in Platanus acerifolia
      leaves varied according to different types of metals, following the order of Zn >
      Cu > Cr > Ni > Pb > Cd. Environmental conditions also had great influence on the
      accumulation of heavy metals. Cd and Cu were mostly found in cement plant and
      mine, respectively, and Cr, Ni, Pb and Zn were significant higher in main road,
      compared with other environmental conditions. The average values of EF for all
      the metals expect Cr in scenic and village area were over 1. The average values
      of EF for all the metals in mine, power plant, main road and cement plant were
      above 3. The overall pollution condition of heavy metals in Huainan City followed
      the order of Cd > Cu > Zn > Ni > Pb > Cr.

PMID- 24881370
TI  - [Implementation results of emission standards of air pollutants for thermal power
      plants: a numerical simulation].
AB  - The emission inventory of air pollutants from the thermal power plants in the
      year of 2010 was set up. Based on the inventory, the air quality of the
      prediction scenarios by implementation of both 2003-version emission standard and
      the new emission standard were simulated using Models-3/CMAQ. The concentrations
      of NO2, SO2, and PM2.5, and the deposition of nitrogen and sulfur in the year of
      2015 and 2020 were predicted to investigate the regional air quality improvement
      by the new emission standard. The results showed that the new emission standard
      could effectively improve the air quality in China. Compared with the
      implementation results of the 2003-version emission standard, by 2015 and 2020,
      the area with NO2 concentration higher than the emission standard would be
      reduced by 53.9% and 55.2%, the area with SO2 concentration higher than the
      emission standard would be reduced by 40.0%, the area with nitrogen deposition
      higher than 1.0 t x km(-2) would be reduced by 75.4% and 77.9%, and the area with
      sulfur deposition higher than 1.6 t x km(-2) would be reduced by 37.1% and 34.3%,
      respectively.

PMID- 24881369
TI  - [Study on the emission characteristics and potential environment hazards of the
      heat-setting machine of the typical dyeing and finishing enterprise].
AB  - To explore the emission characteristics and potential environment hazards of
      volatile organic compounds (VOCs) released from the heat-setting machine of the
      textile dyeing and finishing process, this paper selected five typical printing
      and dyeing enterprises in Zhejiang province as the monitoring subjects, and
      analyzed the actual emissions of 12 kinds of VOCs from the heat-setting machine
      (such as benzene methanol, formaldehyde, etc.), and then preliminarily estimated
      the emissions of VOCs from heat-setting machines of the whole province. Through
      analysis of the ozone generating potential, this paper preliminarily evaluated
      its harm to the environment. The results showed that although the concentration
      of VOCs was low, it contained benzene and formaldehyde, and the highest detection
      concentration could reach 1.53 mg x m(-3) and 15.4 mg x m(-3), which might cause
      serious environmental and human health hazards, Moreover, the VOCs emission from
      heat-setting machines in Zhejiang province was between 200. 9 t x a(-1) and 2
      239.3 t x a(-1), which was dominated by formaldehyde, accounting for about 50%.
      The O3 yield generated from VOCs was between 860.4 t and 16 715. 5 t, with the
      average of 7 729.6 t. The main contribution of VOCs was xylene, toluene and
      formaldehyde, which could account for more than 90%. Furthermore, the VOCs
      emission from heat-setting machines in Shaoxing industry agglomeration area could
      have great influence on the ambient air quality, especially for the O3
      concentration and the minimum contribution rate was 3.1%.

PMID- 24881371
TI  - [On road particle emission characteristics of a Chinese phase IV natural gas
      bus].
AB  - An on-road experimental research was made on a Chinese phase IV natural gas bus
      using a Portable Emission Measurement System (PEMS), and particle emission
      characteristics under different vehicle speed, acceleration and vehicle specific
      power were investigated. The results show that particle number and mass emission
      rates increase and their emission factors decrease while the speed of the bus
      rises. Particle number concentration of different sizes shows multimodal
      logarithmic distribution pattern when the bus runs on all operation conditions
      (idle, low speed, medium speed and high speed), and nucleation mode particle
      account for a large proportion in the total particle number. With the increase of
      acceleration, particle emission rate rises, and it is lower when the bus runs at
      constant speed or slow deceleration condition than that at the fast acceleration
      condition. Furthermore, particle emission rate increases against the absolute
      value of the vehicle specific power (VSP).

PMID- 24881372
TI  - [Chemical compositions of n-alkanols in smoke from rice and maize straw
      combustion].
AB  - Six genotypes of rice straw and four genotypes of maize straw were burned under
      different conditions, and the smoke was collected and n-alkanol in it was
      measured by GC-MS. Results showed that, in the smoke from rice straw flaming
      combustion, n-alkanol was composed of individual compounds from C14 to C34, and
      total contents(sigma) changed in the range of 1 604.4 to 13 889.7 mg x kg(-1).
      The ratio values of amount for n-alkanol with lower carbon number to that for one
      with higher carbon number (L/H) were in the range of 0.02 to 0.09. The values for
      C24/C30, C32/C30, C30/sigma, CPI, and ACL varied from 3.3% to 19.6%, 8.4% to
      19.9%, 53.9% to 72.6%, 8.7 to 21.5, and 29.0 to 30.1, respectively. The abundance
      distribution for the compounds was bimodal with the maximal and the second peaks
      at C30 and C24, respectively. In smoldering smoke of rice straw, individual n
      alkanol from C14 to C34 were also analyzed, with sigma values varying in the
      range of 1 688.7 to 5 168.2 mg x kg(-1). The ratios for L/H, C24/C30, C32/ C30,
      and C30/sigma ranged from 0.08 to 0.14, 31.0% to 70.5%, 6.9% to 17.6%, 39.5% to
      57.8%, respectively. In addition, the CPI and ACL values varied from 10.7 to 17.
      5, and 27.2 to 28.5, respectively. Moreover, the distribution pattern was similar
      to that in flaming smoke. In flaming smoke of maize straw, n-alkanol from C12 to
      C34 were identified, with sigma values being in the range of 852.3 to 2 667.9 mg
      x kg(-1). The values for L/H, C24/C28, C32/C28, C28/sigma, CPI, and ACL varied
      from 0.2 to 1.0, 104.3% to 293.3%, 42.2% to 61.4%, 7.3% to 16.5%, 5.6 to 9.7, and
      23.1 to 26.9, respectively. Besides, the abundance distribution pattern was
      mainly bimodal with a maximal peak at C30, C24 or C22. In the smoldering smoke
      for maize straw, the same individual n-alkanols were found, and the sigma values
      changed from 1493.0 to 8386.9 mg x kg(-1). The values for L/H, C24/C28, C32/C28,
      C28/sigma, CPI and ACL were in the range of 0.2 to 0.3, 53.6% to 217.6%, 21.7% to
      75.9%, 8.8% to 27.3%, 4.2 to 6.5, and 26.3 to 27.2, respectively. Furthermore,
      the distribution pattern was bimodal as well with the highest peak mainly at C30
      and the second one at C24. In brief, obvious discrimination exists among chemical
      compositions of n-alkanol in the straw and smoke. C24/C30, C32/C30, and C30/sigma
      are useful proxies in distinguishing between n-alkanol in airborne aerosol
      deriving from rice straw and one released in rice straw combustion process. L/H,
      C24/C28, C32/C28, and C28/sigma may have a potential in discriminating the
      compounds from maize straw and its burning. L/H is possibly used to makea
      distinction between the organic compounds from rice and maize straws, and/or from
      combustion of the straws.

PMID- 24881373
TI  - [Diurnal and seasonal variations of surface atmospheric CO2 concentration in the
      river estuarine marsh].
AB  - Characteristics of diurnal and seasonal variations of surface atmospheric CO2
      concentration were analyzed in the Minjiang River estuarine marsh from December
      2011 to November 2012. The results revealed that both the diurnal and seasonal
      variation of surface atmospheric CO2 concentration showed single-peak patterns,
      with the valley in the daytime and the peak value at night for the diurnal
      variations, and the maxima in winter and minima in summer for the seasonal
      variation. Diurnal amplitude of CO2 concentration varied from 16.96 micromol x
      mol(-1) to 38.30 micromol x mol(-1). The seasonal averages of CO2 concentration
      in spring, summer, autumn and winter were (353.74 +/- 18.35), (327.28 +/- 8.58),
      (354.78 +/- 14.76) and (392.82 +/- 9.71) micromol x mol(-1), respectively, and
      the annual mean CO2 concentration was (357.16 +/- 26.89) micromol x mol(-1). The
      diurnal CO2 concentration of surface atmospheric was strongly negatively
      correlated with temperature, wind speed, photosynthetically active radiation and
      total solar radiation (P < 0.05). The diurnal concentration of CO2 was negatively
      related with tidal level in January, but significantly positively related in
      July.

PMID- 24881374
TI  - [Partial pressure and diffusion flux of dissolved carbon dioxide in the
      mainstream and tributary of the central Three Gorges Reservoir in summer].
AB  - This study investigated the partial pressure of CO2 (pCO2) in the mainstream of
      the Three Gorges Reservoir and its tributary (Meixi River) in May 2013. Results
      showed that pCO2 in the surface water of the Meixi River and mainstream of the
      Three Gorges Reservoir was 6.8-7.5 Pa and 201.4-210.2 Pa, respectively. At the
      mixing area between the Meixi River and the mainstream of Changjiang, the lowest
      value of pCO2 in surface water was 53.5 Pa, and pCO2 gradually increased
      downwardly. Below 3 m in depth, pCO2 kept the stable value of around 210 Pa.
      Based on the calculation results, the emission flux of CO2 in the Meixi River and
      the mainstream of the central Three Gorges Reservoir was about -7.48 mmol x (m2 x
      d)(-1) and 39.58 mmol x (m2 x d)(-1), respectively. These results showed that the
      Meixi River is a sink for atmospheric CO2, and the mainstream of the Three Gorges
      Reservoir is a source for atmospheric CO2.

PMID- 24881375
TI  - [Emission of CH4, N2O and NH3 from vegetable field applied with animal manure
      composts].
AB  - Greenhouse gas (GHG) emission from vegetable land is of great concern recently
      because agriculture land is one of the major sources contributing to global GHG
      emission. In this study, an experiment of Lactuca sativa L. land applied with
      different animal manure composts was carried out in a greenhouse vegetable land
      located in the surburb of Beijing to monitor the emission of GHG (CH4 and N2O)
      and ammonia in situ, and to analyze the affecting factors of GHG and ammonia
      emission. Results showed that the emission factors (EFs) of CH4 from Treatment
      NRM, RM and CF were 0.2%, 0.027% and 0.004%, respectively,the EFs of N2O from
      these three treatments were 0.18%, 0.63% and 0.74%, respectively, and the EFs of
      ammonia were 2.00%, 3.98% and 2.53%, respectively. CH4 emission flux was
      significantly affected by soil temperature and humidity, while N2O emission flux
      was related to soil temperature, surface temperature and humidity. The emission
      fluxes of CH4, N2O and NH3 were significantly affected by soil moisture, but
      there was little relation between CH4, N2O and NH3 emissions and the ambient
      temperature in the greenhouse.

PMID- 24881376
TI  - [Effects of different iron oxides on methane emission in paddy soil as related to
      drying/wetting cycles].
AB  - This study investigated the effects of iron oxides with different
      crystallinities, ferrihydrite (SF) and hematite (SH), on the methane emission in
      paddy soil of South China under different water conditions, alternative
      drying/wetting cycles (DW) and continuous flooding (CF). The rates of methane
      emission, methane production potential and concentrations of Fe(II) and Fe(III)
      were determined. Results showed that compared with CF, the average methane
      emission rate was greatly inhibited by DW over 61%, and the addition of iron
      oxides reduced methane emission rates by 53%. Under the circumstance of DW and
      iron oxides addition, the combined inhibition effect on the average methane
      emission (65%-94%) and methane production potential (57%-93%) was significantly
      higher than the single effect caused by DW or iron oxides. Interestingly, DW
      coupling poorly crystalline ferrihydrite (SF-DW, 94%) posed a more significantly
      inhibitory effect on the methane emission than coupling crystalline hematite (SH
      DW, 65%). Statistical analysis showed that there was a significantly negative
      correlation between the Fe(III) concentrations and the methane emission rates (R2
      = -0.98, P < 0.01). Experimental results showed that DW facilitated the cyclic
      regeneration of Fe(III), and the Fe(III)/Fe(II) cycle in poorly crystalline
      ferrihydrite was more susceptible to DW than hematite. This study suggested that
      alternative drying/wetting cycles can remarkably enhance the inhibitory effect of
      iron oxides on methane emission from paddy soil, and the coupled suppression
      effect of DW and poorly crystalline ferrihydrite is more obvious than the coupled
      effect of DW and crystalline hematite.

PMID- 24881377
TI  - [Study on the dissolution behavior of biogenic silica in the Changjiang Estuary
      adjacent sea].
AB  - Spatial distribution of biogenic silica (BSi) and factors influencing BSi
      preservation and dissolution in sediments were discussed based on the
      investigation in the Changjiang Estuary adjacent sea. The results showed that the
      contents of BSi were higher in nearshore sediments than those in offshore
      sediments. Terrestrial input, sediment accumulation rate and hydrodynamic
      conditions were the dominant factors affecting BSi preservation in sediments. BSi
      dissolution rate constant showed no obvious change with stations and sediment
      depth. BSi dissolution mainly depended on the following factors including
      undersaturation of silicic acid in pore water compared with BSi solubility,
      organic coating in BSi surface and aluminum concentration in pore water. And
      these factors can influence BSi preservation and the build-up of silicic acid in
      sediments.

PMID- 24881379
TI  - [Lake algae chemotaxonomy technology based on fluorescence excitation emission
      matrix and parallel factor analysis].
AB  - An in vivo three-dimensional fluorescence method for the determination of algae
      community structure was developed by parallel factor (PARAFAC) analysis and
      CHEMTAX. The PARAFAC model was applied to fluorescence excitation-emission matrix
      (EEM) of 23 algae species and 12 fluorescent components were identified according
      to the residual sum of squares and specificity of the composition profiles of
      fluorescent. Based on the 12 fluorescent components, the algae species at
      different growth stages were correctly classified at the division level using
      Bayesian discriminant analysis (BDA). Then the reference fluorescent component
      ratio matrix was constructed for CHEMTAX, and the EEM-PARAFAC-CHEMTAX method was
      developed to differentiate taxonomic groups of algae. When the fluorometric
      method was used for 531 single-species samples, the average correct
      discrimination ratio (CDR) was 99.1% and the correct discrimination ratios (CDRs)
      were 100% at the division level except Chlorophyta, the CDR of which was 97.5%.
      The CDRs for 95 mixtures were above 98.5% for the dominant algae species and
      above 90.5% for the subdominant algae species, with average relative contents of
      69.7% and 26.4%, respectively. This technique would be of great aid when low-cost
      and rapid analysis is needed for samples in a large batch.

PMID- 24881378
TI  - [Phytoplankton community structure and assessment of water quality in the middle
      and lower reaches of Fenhe River].
AB  - To understand the distribution of phytoplankton and the water quality in the
      middle and lower reaches of Fenhe River, 18 sampling sites were selected for
      specimen collection, species identification and data analysis. The results showed
      that: (1) There were 298 species of phytoplankton under the membership of 8
      divisions and 96 genera, among which, Bacillariophyta was the dominant division,
      with a total of 127 species of 27 genera, followed by Chlorophyta, with 104
      species of 41 genera, and Cyanophyta, with 45 species of 20 genera. Only 22
      species of 8 genera belonged to Euglenophyta, Cryptophyta, Pyrrophyta,
      Chrysophyta and Xanthophyta. The number of species in wet season was higher than
      that in dry season at all sites. Dominant species included Cyclotella
      meneghiniana, Synedra acus, Navicula cryptocephala, Nitzschia palea of
      Bacillariophyta, Chlorella vulgaris of Chlorophyta, Oscillatoria tenuis, O.
      amphibia of Cyanophyta, most of which were indicator species of alpha- and beta
      mesosaprobic type. Cell density was higher in wet season and lower in dry season.
      (2) Shannon-Wieaver species diversity index ranged from 1 to 3 basically.
      Margalef species richness index ranged from 0.5 to 2. Pielou evenness index
      ranged 0.3-0.8. (3) During the wet season, most dominant species of Chlorophyta
      and Euglenophyta had higher correlation with chemical oxygen demand (COD),
      conductivity and ammonia nitrogen. The dominant species of Cyanophyta were
      greatly influenced by the contents of water temperature and chromium (Cr). The
      distribution of dominant species of Bacillariophyta was complicatedly related
      with environmental factors. During the dry season, there was a higher correlation
      between the members of Cyanophyta and ammonia nitrogen, total phosphorus, COD.
      The species of Chlorophyta and Euglenophyta were mainly influenced by the
      dissolved oxygen and total phosphorus. The bacillariophytes were mainly related
      with total phosphorus, dissolved oxygen, pH and cadmium (Cd). In conclusion, the
      water was moderately to heavily contaminated in middle and lower reaches of Fenhe
      River and the water quality was eutrophic.

PMID- 24881380
TI  - [Ultraviolet-visible (UV-Vis) spectral characteristics of dissolved organic
      matter (DOM) in soils and sediments of typical water-level fluctuation zones of
      Three Gorges Reservoir areas].
AB  - Dissolved organic matter (DOM) is a very important component in terrestrial
      ecosystem, which also plays a key role in geo-environmental chemistry. A number
      of DOM samples were extracted from soils and sediments samples obtained from
      typical water-level fluctuation zones of Three Gorges reservoir areas.
      Ultraviolet-visible (UV-Vis) absorption spectra were recorded for unveiling the
      geochemical characteristics of DOM based on specific absorption parameters and
      fitting models. Through the results of specific absorption parameters, it was
      suggested that the aromaticity, hydrophobicity and humification degree were lower
      in soils than in the surface sediments, which were also independent of the
      sampling location height and land-use types. Among the four absorption models
      selected, model 2 was the optimal. Meanwhile, different models and fitting
      wavelengths also significantly affected the absorption spectral slope (S value):
      S increased with the decreasing wavelength. Additionally, the correlation among
      different S values obtained from different fitting wavelength ranges was
      significantly different suggesting that the S values in various wavelength ranges
      only indicated the tip of the iceberg of DOM characteristics instead of the
      entirety. Furthermore, the ratio of specific spectral slope (S(R)) indicated
      lower degradation (photo-bleaching or microbial degradation) degree in the
      surface sediments as compared to those in soils and older sediments. The surface
      sediments had higher aromaticity, hydrophobicity, molecular weight and
      photochemical/ biodegradation activity potentials, suggesting fresher DOM, lower
      effect of photobleaching and microbial degradation activities.

PMID- 24881381
TI  - [Distribution of phosphorus in surface sediments from the Yellow River estuary
      wetland].
AB  - Surface sediments were collected from Yellow River estuary wetland. The
      distribution of phosphorus in sediments was analyzed with modified SEDEX. The
      results indicated that the contents of TP in surface sediments varied from 12.12
      micromol x g(-1) to 25.37 micromol x g(-1), and the mean value was 20.70 micromol
      x g(-1), in which the Detrital P and Authigenic P were the main forms. Median
      particle size was closely related with the distribution of phosphors,
      Exchangeable P, Authigenic P and Organic P mainly consisted of smaller sediment
      size, while Detrital P mainly consisted of larger sediment size. The distribution
      of P in sediment was affected by organic matter. Exchangeable P, organic P and
      refractory P increased with the increasing TOC. The bio-available phosphorus
      included exchangeable P, iron-bound P,organic P and ranged from 1.15-6.74
      micromol x g(-1), with an average of 4.27 micromol x g(-1) for all sediment
      samples. The contribution of BAP to TP was 6.35% -30.4%.

PMID- 24881382
TI  - [Characteristics and influencing factors of phosphorus adsorption on sediment in
      Lake Taihu and Lake Hulun].
AB  - Lake Taihu and Lake Hulun in southern and northern China were selected for the
      investigation of differences in the characteristics and influencing factors of
      phosphorus (P) adsorption on the sediments of these two lakes by laboratory
      simulation experiment. The results showed that: (1) The P adsorption capacity of
      sediment in Lake Taihu was much higher than that in Lake Hulun, and the maximum
      adsorption capability for the sediments in these two lakes was 1428.57 mg x kg(
      1) and 56.81 mg x kg(-1), respectively; (2) Compared with the sediments in Lake
      Hulun, the particle diameters from sediments in Lake Taihu were much smaller, and
      their specific surface areas were much larger, so their P adsorption capacity
      were much higher; (3) The equilibrium adsorbed amounts in these two lakes were
      correlated with the total amounts of Al, Fe, Mn (P < 0.05) and significantly
      correlated to the contents of active Al, Fe, Si, Mn (P < 0.01). However, there
      was significant negative correlation between the equilibrium adsorbed amounts and
      total Si contents for the sediments in these two lakes (P < 0.01); (4) The P
      adsorption capacity decreased as pH values in the overlying water increased, and
      the increase of pH values affected the adsorption behavior of phosphorus on the
      sediments in Lake Taihu much more obviously. Therefore, the characteristics of
      sediments and the variations of pH values in the overlying water affected the
      adsorption behavior of P on sediments in lake water body.

PMID- 24881383
TI  - [Linking optical properties of dissolved organic matter with NDMA formation
      potential in the Huangpu River].
AB  - Surface water samples from the Huangpu River were filtered to measure the UV
      absorption and fluorescence spectrum. Dissolved organic carbon (DOC), N
      nitrosodimethylamine (NDMA), and its formation potential (NDMA-FP) were also
      analyzed to explore relationships between the properties of dissolved organic
      matter (DOM) and the formation potential of disinfection byproducts-NDMA in the
      Huangpu River. The study found that: NDMA-FP concentration increased with the
      increasing of DOC concentration (r = 0.487, P < 0.01), but it had negative
      relationships with SUVA254 and HIX (r = -0.605, P < 0.01; r = -0.396, P < 0.01).
      NDMA-FP concentration had positive relationships with the fluorescence intensity
      of protein-like substances such as low-molecular-weight (LMW) tyrosine-like and
      tryptophan-like substances (r = 0.421, P < 0.01; r = 0.426, P < 0.01), but had a
      negative relationship with humic-like substance (r = -0.422, P < 0.01).
      Therefore, NDMA formation potential increases with the increasing DOM content in
      the Huangpu River, which is significantly related with the protein-like
      substances, but decreases with the increasing aromaticity and humification of
      DOM.

PMID- 24881384
TI  - [Reductive debromination of polybrominated diphenyl ethers in aquifier by nano
      zero-valent iron: debromination kinetics and pathway].
AB  - Nano-zerovalent iron (nZVI) approach is effective in the debromination of
      polybrominated biphenyl ethers (PBDEs). The kinetics and degradation pathway are
      the key issues to understand the PBDEs degradation mechanisms. In this study,
      nZVI, synthesized through liquid phase reduction method, coupled with Triton X
      100, could completely debrominate the highly brominated congeners of a commercial
      octa-BDEs mixture within 46 h. The debromination of octa-BDEs could be described
      by means of pseudo-first-order kinetics with the reaction constant (k) of 0.106
      h(-1). In case of lacking the PBDE standards, an effective approach has been
      developed to determine the unknown PBDE congeners using the quantitative
      structure retention relationship (QSRR) model. The retention time of all 39 PBDE
      congeners in a standard mixture was firstly analyzed with gas chromatography
      coupled with an electron capture detector (GC-ECD), and the relative retention
      time (RRT) for each standard was obtained after normalizing the RT by the average
      RT of BDE47 and BDE183. Then a QSRR model was developed by fitting the RRT of
      each PBDE congener and its specific RRT index. The debromination products of octa
      BDEs were identified using this QSRR model and the degradation pathway of octa
      BDEs was elucidated. The results showed that in the stepwise reductive
      debromination process of PBDEs by nZVI, meta-debromin was facile to be degraded.

PMID- 24881385
TI  - [Influencing factors and reaction mechanism of chloroacetic acid reduction by
      cast iron].
AB  - The chloroacetic acids are ubiquitous present as a class of trace chlorinated
      organic pollutants in surface and drinking water. Most of chloroacetic acids are
      known or suspected carcinogens and, when at high concentrations, are of great
      concern to human health. In order to economically remove chloroacetic acids, the
      degradation of chloroacetic acids by cast iron was investigated. Moreover, the
      effect of iron style, pretreatment process, shocking mode and dissolved oxygen on
      chloroacetic acids reduced by cast iron was discussed. Compared to iron source
      and acid pretreatment, mass transfer was more important to chloroacetic acid
      removal. Dichloroacetic acid (DCAA) and monochloroacetic acid (MCAA) were the
      main products of anoxic and oxic degradation of trichloroacetic acid (TCAA) by
      cast iron during the researched reaction time, respectively. With longtitudinal
      shock, the reaction kinetics of chloroaectic acid removal by cast iron conformed
      well to the pseudo first order reaction. The anoxic reaction constants of TCAA,
      DCAA and MCAA were 0.46 h(-1), 0.03 h(-1) and 0, and their oxic constants were
      1.24 h(-1), 0.79 h(-1) and 0.28 h(-1), respectively. The removal mechanisms of
      chloroacetic acids were different under various oxygen concentrations, including
      sequential hydrogenolysis for anoxic reaction and sequential hydrogenolysis and
      direct transformation possible for oxic reaction, respectively.

PMID- 24881386
TI  - [Effect of phosphorus recovery on phosphorous bioaccumulation/harvesting in an
      alternating anaerobic/aerobic biofilter system].
AB  - To improve the phosphorus (P) removal/recovery efficiency of a biological P
      removal system, the study used an alternating anaerobic/aerobic biofilter system
      to treat synthetic domestic sewage with a low carbon (C) to P ratio. The effects
      of using periodical carbon source amplification for P recovery on the P removal
      efficiency and the microbial characteristics within the biofilm were
      investigated. Intracellular storage polymer dyeing, scanning electron microscopy
      (SEM) observation and fluorescence in situ hybridization (FISH) methods were
      employed to characterize the changes of microbial communities in the biofilm
      during three continuous operation cycles of P bio-accumulating-P recovery (PB
      PR). The results showed: through three cycles of operation process of PB-PR, the
      P removal efficiency of biofilter was increased from 60.3%, 82.9%, 86.6% (before
      P harvesting) to 87.2%, 91.2%, 93.5% (after P harvesting), respectively; the
      dominant microbial community morphotypes within the biofilter transformed from
      big cocci to small cocci, bacilli and filamentous and the group of phosphate
      accumulating organisms (PAOs) got rising predominance, which was increased from
      43% to 70% after three times of PB-PR; the proportion of PAOs in the biofilm
      increased unceasingly with the height of the up-flow biofilter. The results
      showed that the periodical carbon source amplification could improve the P
      removal efficiency of the biofilter and help the PAOs to become the dominant
      bacteria within the biofilm.

PMID- 24881387
TI  - [Effects of pretreatment methods on corncob as carbon source for
      denitrification].
AB  - The corncob was pretreated by 1.5% NaOH, 1% H2SO4, 1.5% H2O2 and alkaline
      hydrogen peroxide (caustic soda solution with 1.5% H2O2) combined with
      ultraviolet radiation. And the characteristics of carbon released,
      denitrification and bio-attachment capability of using pretreated corncob as
      carbon source for denitrification were studied in carbon release and
      denitrification experiments in laboratory scale. The results showed that the
      denitrification efficiency and the utilizability of the carbon released by the
      corncob pretreated by alkali or alkaline hydrogen peroxide were significantly
      enhanced. Especially, for the alkali pretreatment method, the nitrate removal
      rate could still maintain higher than 90% after 41 days of denitrification
      experiments. Therefore, the alkali pretreatment method could improve the carbon
      release performance of the corncob and is beneficial for microbial adsorption and
      carbon source utilization.

PMID- 24881388
TI  - [Start-up by inoculation and operation of a CANON reactor with haydite as the
      carrier].
AB  - A CANON reactor with haydite as the carrier was started by incubating sludge from
      another CANON reactor and using synthetic inorganic ammonia rich wastewater as
      the raw water. Both start-up and operation were studied. The result showed that
      haydite can be a suitable carrier for CANON reactor. With this carrier, start-up
      of CANON reactor can be completed in 60 days with total nitrogen removal load up
      to 0.79 kg x (m3 x d)(-1), when the reactor was equipped with a water jacket to
      maintain the water temperature at 30 degrees C +/- 1 degrees C, and pH at 7.00
      8.08, hydraulic retention time of 9 hours. The critical range of dissolve oxygen
      for CANON reactor was 1.12-1.69 mg x L(-1), and both characteristics of short-cut
      nitrification and ANAMMOX were stable. However, the CANON reactor can be instable
      if dissolve oxygen concentration increased above this range. Although the ratio
      of nitrate variation to total nitrogen variation (deltaNO3(-) -N/deltaTN) was
      0.150-0.204, which deviated a little from its theoretical value, 0.127. The
      performance of CANON reactor kept relatively stable. The total nitrogen removal
      efficiency was up to 75.56% while total nitrogen removal load was 0.97 kg x (m3 x
      d)(-1), which means the temperature for CANON reactor can be decreased to 25
      degrees C at least.

PMID- 24881389
TI  - [Diversity of operation performance and microbial community structures in MBRs
      and CAS processes at low temperature].
AB  - In this paper, the performance of membrane bioreactors (MBR) and conventional
      activated sludge (CAS) processes at low temperature was investigated by analyzing
      their effluent quality and microbial viability. 454 high-throughput
      pyrosequencing was also applied to study the microbial community structures. The
      results of three systems (two MBRs: R1 with high sludge concentration, R2 with
      low sludge concentration, and one CAS: R3) showed that the average removal rate
      of NH4(+) -N was 99.7%, 99.7% and 59.7%, respectively, and the average removal
      rate of TN was 85.2%, 56.1% and 58.8%, respectively. R2 showed the highest
      specific ammonium uptake rate (SAUR), followed by R1 and R3; R1 showed the
      highest specific nitrate uptake rate (SNUR), followed by R2 and R3. It could be
      concluded that MBRs with high sludge concentration had a better performance of
      nitrogen removal under low temperature operation. 454 high-throughput
      pyrosequencing analysis revealed that the microbial richness was R2 > R3 > R1,
      and the microbial diversity was R2 > R1 > R3 at 97% sequence identity. The
      microbial structure and bacterial abundance were quite different between MBR and
      CAS systems. The dominant nitrifier in this research was Nitrospira, and the
      total relative abundance of nitrifiers in R1, R2, R3 was 1.22%, 1.64% and 0.15%,
      respectively. The Zoogloea, Thauera, Comamonadaceae and Comamonas might be the
      dominant denitrifers in this study, and the total relative abundance of
      denitrifier in R1, R2, and R3 was 5.8%, 4.52% and 15.21% respectively. MBR's
      characteristics of long solid retention time, high sludge concentration and low
      total nitrogen loading well supported the accumulation of nitrifiers and
      denitrifiers, and improved the performance of biological nitrogen removal at low
      temperature.

PMID- 24881390
TI  - [Enhanced hydrolysis and acidification of waste activated sludge by alkyl
      polyglycosides].
AB  - The effects of biosurfactant alkyl polyglycosides (APG) on the hydrolysis and
      acidification of waste activited sludge including dosage of APG and hydrolysis
      time were investigated. It was found that APG reduced the tension of sludge
      hydrolysate, promoting sludge hydrolysis. The concentrations of SCOD, protein and
      soluble carbonhydrate reached the maximum within 12 h at the optimal dosage of
      0.2 g x g(-1) TSS, rising from 4 280.2, 1 122.9 and 246.5 mg x L(-1) to 6481.1, 1
      639.3 and 1205.8 mg x L(-1), respectively, and the short-chain fatty acids
      (SCFAs) concentration increased from 1309.9 mg x L(-1) to 2221.6 mg x L(-1)
      simultaneously, the percentage of individual SCFA changed as well, and the time
      required to reach the maximal SCFAs concentration will be prolonged with the
      increase of dosage. With increasing APG dosage, a-glucosidase relative enzyme
      activities increased from 1.5 to 2.5, while protease relative enzyme activity
      increased from 1.4 to 1.9 at low dosages and decreased to 1.5 at high dosages.
      Regardless of the biosurfactant APG, alpha-glucosidase and protease enzyme
      activities decreased along with the hydrolysis time. The pH showed a tendency of
      first decreasing and then increasing.

PMID- 24881391
TI  - [Effect of substrate concentration on pathogen indicators inactivation during
      thermophilic anaerobic digestion].
AB  - Because excess sludge contains high density of pathogens, it has to be treated to
      reduce pathogens before being disposed for land application. In this study, the
      effect of substrate concentration on pathogen inactivation during thermophilic
      anaerobic digestion was investigated. The results show that, with the increase of
      substrate concentration, VFAs and cumulative methane production increased. The
      density of total coliforms in the suspension liquid has a 2.0-3.0 orders of
      magnitude decline and fecal coliforms has 1.8-3.3 orders of magnitude decline
      after 28 days thermophilic anaerobic digestion at substrate concentration of 28
      84 g x L(-1) and temperature of 55 degrees C. More than 99% of total coliforms
      and fecal coliforms have been killed after 28 days digestion. Salmonella spp. was
      not detected in the suspension and solid after anaerobic digestion. When
      substrate concentration was higher than 45 g x L(-1), the inactivation of total
      coliforms and fecal coliforms declined.

PMID- 24881392
TI  - [Pollution evaluation and health risk assessment of heavy metals from atmospheric
      deposition in Lanzhou].
AB  - In order to evaluate the contamination and health risk of heavy metals from
      atmospheric deposition in Lanzhou, samples of atmospheric deposition were
      collected from 11 sampling sites respectively and their concentrations of heavy
      metals were determined. The results showed that the average contents of Cu, Pb,
      Cd, Cr, Ni, Zn and Mn were 82.22, 130.31, 4.34, 88.73, 40.64, 369.23 and 501.49
      mg x kg(-1), respectively. There was great difference among different functional
      areas for all elements except Mn. According to the results, the enrichment factor
      score of Mn was close to 1, while the enrichment of Zn, Ni, Cu and Cr was more
      serious, and Pb and Cd were extremely enriched. The assessment results of
      geoaccumulation index of potential ecological risk indicated that the pollution
      of Cd in the atmospheric deposition of Lanzhou should be classified as extreme
      degree, and that of Cu, Ni, Zn, Pb as between slight and extreme degrees, and Cr
      as practically uncontaminated. Contaminations of atmospheric dust by heavy metals
      in October to the next March were more serious than those from April to August.
      Health risk assessment indicated that the heavy metals in atmospheric deposition
      were mainly ingested by human bodies through hand-mouth ingestion. The non-cancer
      risk was higher for children than for adults. The order of non-cancer hazard
      indexes of heavy metals was Pb > Cr > Cd > Cu > Ni > Zn. The non-cancer hazard
      indexes and carcinogen risks of heavy metals were both lower than their threshold
      values, suggesting that they will not harm the health.

PMID- 24881393
TI  - [Ecological risk assessment of organophosphorus pesticides in aquatic ecosystems
      of Pearl River Estuary].
AB  - The risk quotient method and a probabilistic risk assessment method were applied
      for assessing aquatic ecological risk of nine organophosphorus pesticides,
      including thimet, dichlorovos, disulfoton, dimethoate, dimethyl parathion,
      chlorpyrifos, ethoprophos, sumithion and malathion on eight aquatic organisms in
      the Pearl River Estuary. Results using the risk quotient method revealed that the
      risk level of opossum shrimp was the highest among eight aquatic organisms of the
      Pearl River Estuary. The risk of water flea and midge was in medium level,
      followed by the rest six aquatic organisms, including diatom, oyster, carp,
      catfish and eel, which were in the low risk by the examined organophosphorus
      pesticides. It was found that thimet made the largest contribution to total
      aquatic ecological risk among nine organophosphorus pesticides to every organism.
      The results from probabilistic risk assessment showed that the total ecological
      risk in high water period was higher than that in low water period determined by
      the HC5 under the 95% confidence level. The largest contribution of thimet to
      total aquatic ecological risk subject to the HC5 in 50% confidence level was
      regarded as the toxic reference value. The probabilistic risk of a single
      contaminant showed that thimet and disulfoton were harmful to exceeded 10%
      organisms in the estuarine. The probabilistic risk of nine pesticides mixture in
      high water period was also higher than that in low water period, and both risks
      were greater than 5% which exceeded safety threshold for 95% organisms in the
      Pearl River Estuary.

PMID- 24881394
TI  - [Source characteristics and contamination evaluation of heavy metals in the
      surface sediments of Haizhou Bay].
AB  - Based on the investigation data from 17 sampling stations in the sea area of
      Haizhou Bay in 2009, the geo-statistics analysis was used to estimate the source
      characteristics of heavy metals in surface sediments, and the potential
      ecological risk index was applied to evaluate the status of the ecological risk.
      The contents of heavy metals showed a landward as well as northeastward
      increasing trend. The spatial distribution characteristics reflected that land
      based inputs of pollution were the main sources of heavy metals. According to the
      analysis of Pearson correlation coefficients, the contents of organic carbon,
      sulfide and grain-size of sediments were important factors for the content and
      distribution of heavy metals. The results of potential ecological risk evaluation
      indicated that the Haizhou bay as a whole can be ranked as "moderate potential
      ecological risk". The high risk zone was in the coastal waters between Longwang
      estuary and Linhong estuary. The sequence of the potential ecological risk posed
      by the metals was Cd > As > Cu > Pb > Cr > Zn. Cd was the major pollutant among
      the metals in consideration, while the pollution related to others was less
      significant.

PMID- 24881395
TI  - [Health risk induced by estrogens during unplanned indirect potable reuse of
      reclaimed water from domestic wastewater].
AB  - The estrogenic endocrine disruptors in reclaimed water from domestic wastewater
      may induce health risks to human being, when reclaimed water is used for
      augmentation of drinking water unplannedly and indirectly. This study
      investigated changes in concentrations of estrone, estradiol, 17alpha-ethinyl
      estradiol, bisphenol A, nonylphenol and octylphenol in reclaimed water during the
      reuse of reclaimed water for augmentation to water source such as lakes and
      reservoir via river. Thereafter, health risk induced by estrogens during the
      resue of reclaimed water was evaluated. The concentration of estrogen in
      secondary effluent ranged 0.1-100 ng x L(-1). The highest concentrations of
      bisphenol A and nonylphenol reached up to 1-10 microg x L(-1). During the
      indirect reuse of reclaimed water as potable water, the dilution and degradation
      in river and lake, and the removal by drinking water treatment process could
      change the concentrations of estrogen. The non-carcinogenic risks of estrone,
      estradiol, bisphenol A, nonylphenol and octylphenol were lower than 1. When the
      hydraulic retention time of 17alpha-ethinyl estradiol (EE2) in lakes and
      reservoir was higher than 30 days, the non-carcinogenic risk of EE2 was lower
      than 1 in most cases. When the hydraulic retention time of EE2 in lakes and
      reservoir was less than 30 days and the percentages of reclaimed water in
      drinking water were higher than 50%, the non-carcinogenic risk induced by EE2 was
      higher than 1 in 20%-50% samples. This indicated that the risks of EE2 should be
      concerned.

PMID- 24881396
TI  - [Distribution characteristics and erosion risk of nitrogen and phosphorus in
      soils of Zhuangmu town in Lake Wabuhu basin].
AB  - To understand the loss risk of soil erosion in the Zhuangmu town in Lake Wabuhu
      watershed, concentration and spatial distribution of nitrogen and phosphorus in
      162 surface soil samples collected from the farmlands in ten administrative
      villages of the town were investigated. The risk assessment was conducted by
      using the nitrogen and phosphorus index method after speciation analysis of soil
      nitrogen and phosphorus. Based on ArcGIS technology, the spatial interpolation of
      total nitrogen (TN), total phosphorus (TP), and bioavailable nitrogen and
      phosphorus contents as well as nitrogen and phosphorus index values were
      performed by means of Kriging interpolation. The results show that, generally,
      average contents of TN and TP were obtained at 1.67 g x kg(-1) and 0.71 g x kg(
      1), respectively. And the mean concentration of bioavailable nitrogen and
      phosphorus were estimated at 0.26 g x kg(-1) and 0.33 g x kg(-1), accounting for
      14.93% and 47.30% of TN and TP contents, respectively. Spatially, the samples
      with high concentration of TN were mostly from Houji, Yangwan and Liuqian
      villages, whereas the samples sites with higher contents of TP located in Houji,
      Yangwan and Zaolin villages. The mean values of nitrogen index (NI) and
      phosphorus index (PI) for the whole town are 2.11 and 2.13, respectively.
      According to the numeric size of NI and PI, ten villages ranged in the order of
      Yangwan > Zhuangmu > Xueqiao > Liuqian > Lizhuang > Jinqiao > Zaolin > Zhangwei >
      Houji > Xugang village. In general, the soil nitrogen loss is dominated by low
      and medium risks in the Zhuangmu town, and high risk sporadically appears in
      local area of the Yangwan village. Like the nitrogen, soil phosphorus loss risk
      also gives priority to low, and above medium risk concentrates in the Yangwan
      village as well.

PMID- 24881397
TI  - [Distribution and risk assessment of mercury species in soil of the water-level
      fluctuating zone in the Three Gorges Reservoir].
AB  - To investigate pollution level and ecological risk of mercury in soils of the
      water-level-fluctuating zone in the Three Gorges Reservoir Region, 192 surface
      soil samples from 14 counties (districts) in Chongqing were obtained.
      Concentrations of THg and Hg species, bioavailable Hg were analyzed and
      discussed. Geoaccumulation index (I(geo)) and Hakanson potential ecological risk
      index (E(r)) were applied to assess the pollution status and potential ecological
      risk of THg and Hg species, respectively. The results showed that significant
      differences in the concentration of THg were found in soils of water-level
      fluctuating zone in the Three Gorges Reservoir. The THg concentration ranged from
      22.4 to 393.5 microg x kg(-1), with an average of (84.2 +/- 54.3) microg x kg(
      1). 76.6% of the samples' THg content was higher than the soil background value
      in the Three Gorges Reservoir Region. The percentage of five mercury species
      (water-soluble Hg, HCl-soluble Hg, KOH-soluble Hg, H2O2-soluble Hg, residue Hg)
      in soils were 4.1%, 15.5%, 18.3%, 10.9%, 51.3%, respectively. The average
      concentrations of bioavailable mercury varied between 19.7-36.6 microg x kg(-1),
      and the percentage of bioavailable Hg was 22.1%-51.6% of THg. According to the
      geoaccumulation index, the soils were lightly polluted by Hg. Hakanson single
      potential ecological risk index evaluation showed that Hg species had a low
      potential ecological risk, moreover, soils of water-level-fluctuating zone in the
      Three Gorges Reservoir were at low ecological risk levels as evaluated by
      bioavailable Hg. While, the assessment results based on THg of soils was much
      higher than that based on the Hg species. Two methods of evaluation showed that
      the I(geo) and E(r) values calculated based on the Hg species better reflected
      the actual pollution levels of soils and its hazard to aquatic organisms.

PMID- 24881398
TI  - [Health risk assessment of soil heavy metals in residential communities built on
      brownfields].
AB  - Nine residential communities which were built on different brownfields in a city
      of Henan Province were chosen to investigate the health risks of heavy metals
      (As, Hg, Cd, and Pb) in surface soils. Concentrations of soil heavy metals were
      measured according to the methods described in the national standard. Based on
      the health risk models recommended by the U. S. Environmental Protection Agency
      (US EPA), non-carcinogenic and carcinogenic health risks of soil heavy metals
      were assessed. The results showed that compared with the original brownfields,
      the heavy metal concentrations in soils and their health risks in residential
      communities built on brownfields were significantly improved, and the
      concentrations and health risks of soil heavy metals in these communities were
      all higher than those in non-brownfield residential communities. The HQ and HI
      values of soil heavy metals in all the residential communities were lower than 1,
      which indicated that there was no non-carcinogenic risk in these communities.
      Meanwhile, the values of CR and TCR were slightly higher than the standard
      suggested by the US EPA, indicating that slight carcinogenic risks in the
      communities, but these values were lower than the lenient standard proposed by
      some experts. The HI value of the four metals for children was exactly seven
      times higher than that for adults. The contribution rate of HQ(As) to HI was
      about 75%, CR(AS) to TCR was about 80%, and therefore arsenic was the crucial
      factor for carcinogenic and non-carcinogenic risk in the residential communities
      of the city.

PMID- 24881399
TI  - [Study on ecological risk assessment technology of fluoride pollution from arid
      oasis soil].
AB  - According to translocation regulation of fluoride in the typical oasis soil-plant
      system under field, an ecological risk assessment model of fluoride was
      established, and this model was used to assess ecological risk to fluoride
      pollution from suburban oasis soils in Baiyin City, which was specifically
      expressed with the potential ecological risk of bioavailability (ER(bc)) model to
      assess ecological risk of fluoride pollution in oasis regions. Results showed
      that the ecological risk indices of fluoride pollution from this region were 1.37
      24.81, the level of risk at most sites was high to very high, the average
      ecological risk index was 11.28, belonged to very high risk. This indicated that
      in the suburb soil of Baiyin City needs to be concerned about the remediation of
      fluoride pollution.

PMID- 24881400
TI  - [Rainfall process and nitrogen input in three typical forests of Jinyun
      Mountain].
AB  - Evergreen broad-leaved forest (EBF), bamboo forest (BF) and mixed conifer and
      broadleaved forest (MF) were selected as objects of study on Jinyun Mountain from
      May to October 2012. The main contents were to analyze the rainfall process and
      nitrogen input of atmospheric rainfall, throughfall and stemflow. The results
      showed that: (1) During the research period, the total precipitation was 564. 88
      mm, and throughfall of EBF, BF and MF were 74.0%, 85.0% and 71.6% of rainfall,
      respectively, and stemflow were EBF (1.9%), BF(10.3%) and MF (1.6%),
      respectively. The relationship between throughfall, stemflow and atmospheric
      rainfall could be described by a significant linear equation (P < 0.05), and both
      throughfall rate and stemflow rate had an obvious logarithmic function
      relationship with atmospheric rainfall (P < 0.05). (2) The concentration of NO3(
      ) and NH4(+) of throughfall and stemflow were higher than those of atmospheric
      rainfall, of which the three typical forests ranked as MF > EBF > BF. The total
      inorganic nitrogen input of throughfall and stemflow were EBF (14.93 kg x hm(
      2)), BF (15.31 kg x hm(-2)) and MF (18.93 kg x hm(-2)), respectively. (3) There
      was a significant linear relationship between inorganic nitrogen input and
      throughfall, stemflow for three typical forest stands (P < 0.05).

PMID- 24881401
TI  - [Effects of land use and landscape pattern on nitrogen and phosphorus exports in
      Lanlingxi Watershed of the Three Gorges Reservoir Area, China].
AB  - The temporal and spatial characteristics of N, P exports and effects of land use
      and landscape pattern on N, P exports were analyzed in the Lanlingxi Watershed of
      the Three Gorges Reservoir Area. The results showed that the TN, TP and NO3(-) -N
      were mainly generated by non-wood forest, the N, P exports in flood period (June
      to September) were significantly higher than the non-flood period (January to
      May). The NH4(+) -N export was derived from the residential area in the non-flood
      period, while from non-wood forest in the flood period. In addition, the
      performance of samples N, P exports with forest distributed were lower in both
      two periods. Also, the proportion of forest significantly negatively correlated
      with NO3(-) -N, TP in the non-flood period and TN, TP in the flood period. The
      residential area proportion notably positively correlated with NO3(-) -N, TN in
      non-flood period and NO3(-) -N, TN, TP in the flood period. The non-wood forest
      proportion also significantly positively correlated with NH4(+) -N, TN in the
      flood period. Moreover, PD closely positively correlated with N exports in non
      flood period, with NO3(-) -N, NH4(+) -N in flood period. The CONT index strongly
      negatively correlated with N exports in flood period and TP in non-flood period.
      However, the proportions of farmland, unused land and the indices of ED were
      relatively weakened with N, P exports in both periods, while SHMN and water
      proportion did not show any positive or negative correlation. Moreover, the
      regression fitting degree of NH4(+)-N was superior to NO3(-) -N, TN and TP with
      the adjust R2 of 0.885 and 0.969 in two periods, while the regression relation
      was better than that of non-flood period. The result of redundancy analysis
      further demonstrated that the landscape fragmentation caused by patches types of
      different land uses could better explain impacts on the exports of nitrogen and
      phosphorus. The two canonical axes accumulated explained the 90% proportion of
      the variables and the highest contribution was PD, which was an important
      indicator for watershed water quality assessment and prediction.

PMID- 24881402
TI  - [Changes and influencing factors of the soil organic carbon in farmland in the
      last 30 years on Hilly Loess Plateau: a case study in Zhuanglang County, Gansu
      Province].
AB  - By analysing the sampled data and the results of the second national soil survey
      by the mid 80 s in Zhuanglang County, the article studied on the changes and
      influencing factors of the soil organic carbon in farmland of this area in the
      last 30 years. Farmland samples of top soil (0-20 cm) were collected and analyzed
      in July 2011. The results showed that (1) The average contents of the soil
      organic carbon in the county's farmlands were 6.80 g x kg(-1) in 1985 and 8.90 g
      x kg(-1) in 2011. It increased by 30.9% in the past 30 years, which appeared as a
      carbon sink effect. The area of increasing contents of soil organic carbon
      accounted for about 90% of the county's farmland area. (2) Under the available
      management measures and farmland input, the loessal soil organic carbon stability
      level was 11.0 g x kg(-1), The SOC accumulation rate showed that the farther the
      SOC was from the stability level the more quickly it changed, and the closer the
      SOC was from the stability level the slower it changed. (3) The SOC changes was
      affected by the altitude, the primary content of organic carbon, and the soil
      types and so on, in which the greatest contribution factor was the altitude, the
      influence of the primary content of organic carbon, soil type, production and
      organic fertilizer on soil organic carbon change was smaller, and the slope
      aspect had the smallest effect on soil organic carbon change.

PMID- 24881403
TI  - [Organic carbon and carbon mineralization characteristics in nature forestry
      soil].
AB  - Through field investigation and indoor analysis, the organic carbon content and
      organic carbon mineralization characteristics of six kinds of natural forest soil
      were studied, including the pine forests, evergreen broad-leaved forest,
      deciduous broad-leaved forest, mixed needle leaf and Korean pine and Chinese pine
      forest. The results showed that the organic carbon content in the forest soil
      showed trends of gradual decrease with the increase of soil depth; Double
      exponential equation fitted well with the organic carbon mineralization process
      in natural forest soil, accurately reflecting the mineralization reaction
      characteristics of the natural forest soil. Natural forest soil in each layer had
      the same mineralization reaction trend, but different intensity. Among them, the
      reaction intensity in the 0-10 cm soil of the Korean pine forest was the highest,
      and the intensities of mineralization reaction in its lower layers were also
      significantly higher than those in the same layers of other natural forest soil;
      comparison of soil mineralization characteristics of the deciduous broad-leaved
      forest and coniferous and broad-leaved mixed forest found that the differences of
      litter species had a relatively strong impact on the active organic carbon
      content in soil, leading to different characteristics of mineralization reaction.

PMID- 24881404
TI  - [Dynamic change of phosphorus leaching of neutral purple soil at different re
      wetting rate].
AB  - Re-wetting was one of the most common forms of abiotic stresses experienced by
      soils. To investigate the effects of soil re-wetting rate on phosphorus (P)
      leaching and the relationship between soil microbial biomass carbon (MBC) and
      forms of P in leachate; five kinds of neutral purple soils of different
      fertilizer treatments were analyzed using simulating lab test at re-wetting rate
      of 0 h, 2 h, 4 h, 24 h and 48 h. The results showed that: (1) The lowest content
      of MBC appeared at the rate of 2 h during the soil re-wetting process, and the
      content of MBC increased with the reducing re-wetting rate. (2) Slower re-wetting
      helped to enhance soil microbial activity and the enhancement effect of organic
      fertilizer with NPK fertilizer (MNPK) was more significant. (3) The P leaching
      events of all fertilizer treatments occurred mainly at rapid re-wetting rates
      such as 0 h, 2 h, 4 h. Slower re-wetting was an important measure to prevent P
      leaching especially for the soils applied with chemical fertilizers, and it was
      of great significance in the field management of P. (4) Dissolved organic
      phosphorus (DOP) was the primary leaching part in leachate, and the variation
      range of ratio of total dissolved phosphorus (TDP) to total phosphorus (TP) and
      DOP to TP was 35.42%-85.99% and 29.74%-78.58% respectively. (5) With the reducing
      of re-wetting rate, significant negative correlation was observed between MBC and
      TP, TDP as well as DOP in the leachate (P < 0.05). To sum up, it was speculated
      that the P in soil leachate mainly came from soil microorganisms.

PMID- 24881405
TI  - [Effects of thiourea on pH and availability of metal ions in acid red soil].
AB  - Through the simulation research, the effects of application of thiourea and urea
      on pH and availability of metal ions in acid red soil were studied, and the
      results showed that after applying urea, the soil pH increased in the first
      experimental stage and then reduced gradually to a low level, however, decreased
      trends of soil pH values were inhibited by the application of thiourea,
      especially when the concentration of thiourea reached to 5.0 mmol x kg(-1) dry
      soil, the soil pH was stable at high level, which exceeded to 6.0. It proved that
      the application of thiourea could inhibit the soil acidification due to urea
      application. After applying urea with different concentrations of thiourea, the
      available contents of Zn and Al decreased with the increasing concentration of
      thiourea, nevertheless, when the concentration of thiourea reached to 5.0 mmol x
      kg(-1), the available content of Mn was stable at high level which was over 110
      mg x kg(-1). In addition, the results showed a highly significant negative
      correlation between the soil pH and the available content of Cu, Zn and Al, but
      for Mn, no discipline was found between the soil pH and the availability after
      applying thiourea. Moreover, the soil pH became higher after applying urea with
      thiourea compared to add urea only, which led to the decreasing of available
      content of Al, and it was benefited for the control of the phytotoxic effect of
      Al. The available content of Mn in the soil not only depended on soil pH but also
      the content of thiourea due to its redox and complexing reaction with Mn.

PMID- 24881406
TI  - [Growth responses of six leguminous plants adaptable in Northern Shaanxi to
      petroleum contaminated soil].
AB  - To select appropriate native species in Northern Shaanxi for phytoremediation,
      the growth index of six kinds of leguminous plants planted in petroleum
      contaminated soils were investigated through pot culture. Petroleum
      concentrations were set at 0, 5 000, 10 000, 20 000, 40 000 mg x kg(-1)
      respectively with three replicates. Using different levels of seed germination
      rate, germination time, individual height, wilting rate, dry weight and
      chlorophyll content in leaves of tested plants as the ecological indicator. The
      results showed that tested plants have significantly different responses to
      petroleum pollution. Compared with those planted in clean soils, seed germination
      rate and individual height were promoted when petroleum concentration was lower
      than 5000 mg x kg(-1), but inhibition occurred when petroleum concentrations were
      higher than 10000 mg x kg(-1). Strong endurance of Medicago sativa was observed
      to petroleum polluted soil, especially at lower petroleum concentration. Leaf
      wilting of Robinia pseudoacacia was unobserved even when petroleum concentration
      was 40 000 mg x kg(-1), thus displaying the potential of remediating petroleum
      contaminated soils. The petroleum concentration was significantly and negatively
      correlated with seed germination rate, individual height and dry weight, but
      positively correlated with chlorophyll content in leaves.

PMID- 24881407
TI  - [Plant N status in the alpine grassland of the Qinghai-Tibet Plateau: base on the
      N: P stoichiometry].
AB  - Plants from different functional groups show distinct response to nitrogen (N)
      addition, however, the patterns and underlying mechanisms across the natural N
      availability gradient remain unexplored. In present studies, effects of soil N
      fertility on aboveground N pools and production were examined, and the N: P
      stoichiometry was compared among forbs, graminoids, and legumes on an alpine
      grassland located in northeast of Qinghai-Tibet Plateau. Mean N: P ratios of the
      whole community in 2008 and 2009 were 9. 83 and 11.57, respectively, indicating
      that the sub-alpine grassland was mainly N-limited. The partial redundancy
      analysis (partial RDA) showed that the biomass percentage of forbs increased,
      while those of legumes and graminoids decreased with the soil N availability. It
      suggested that legumes and graminoids were more competitive than forbs in the
      natural N-limited grassland, which may be due to the N2-fixation ability and high
      nutrient use efficiency, respectively. Under the projected increasing N
      deposition, the vegetation tended to shift from graminoids and legumes to forbs.
      Significant relationships were found between the percentage of legumes biomass
      and N: P (phosphorus) ratio for the whole community and non-legumes, indicating
      that legumes could improve the community N status as well as non-legumes N status
      on the alpine grassland.

PMID- 24881408
TI  - [Development and succession of artificial biological soil crusts and water
      holding characteristics of topsoil].
AB  - In order to understand the improving effects of cyanobacterial inoculation on
      water retention of topsoil in desert regions, this work focused on the
      development and succession of biological soil crusts and water holding
      characteristics of topsoil after cyanobacterial inoculation in Qubqi Desert. The
      results showed that after the artificial inoculation of desert cyanobacteria,
      algal crusts were quickly formed, and in some microenvironments direct succession
      of the algal crusts to moss crusts occurred after 2-3 years. With the development
      and succession of biological soil crusts, the topsoil biomass, polysaccharides
      content, crust thickness and porosity increased, while the soil bulk density
      decreased. At the same time, with crust development and succession, the topsoil
      texture became finer and the percents of fine soil particles including silt and
      clay contents increased, while the percents of coarse soil particles (sand
      content) decreased proportionately. In addition, it was found that with crust
      development and succession, the water holding capacity and water content of
      topsoil showed an increasing trend, namely: moss crust > algal crusts > shifting
      sand. The water content (or water holding capacity) in algal and moss crusts were
      1.1-1.3 and 1.8-2.2 times of those in shifting sand, respectively. Correlation
      analysis showed that the water holding capacity and water content of topsoil were
      positively correlated with the crust biomass, polysaccharides content, thickness,
      bulk density, silt and clay content; while negatively correlated with the
      porosity and sand content. Furthermore, stepwise regression analysis showed that
      the main factor affecting water content was the clay content, while that
      affecting water holding capacity was the porosity.

PMID- 24881409
TI  - [Carbon dioxide assimilation potential, functional gene amount and RubisCO
      activity of autotrophic microorganisms in agricultural soils].
AB  - Carbon dioxide (CO2) assimilation by autotrophic microorganisms plays a
      significant role in carbon sequestration in terrestrial ecosystems. Here,
      experiments were carried out to determine the contribution of autotrophic
      microorganisms to atmospheric CO2 fixation in 6 representative agricultural
      soils. Soils were incubated continuously in an atmosphere of 14CO2 and the
      distribution of labeled C into soil organic carbon (14C-SOC) was determined after
      110 d. Meanwhile, the amounts of the cbbL genes were determined by Quantitative
      PCR and the RubisCO activity was measured in different soils. The results showed
      that substantial amounts of 14CO2 were fixed into 14C-SOC (ranged 10.63-133.81 mg
      x kg(-1) after 110 d of continuous labeling, with an annual, global rate of about
      0.57-7.3 Pg. The microbially fixed C was also incorporated into the active carbon
      pool [the dissolved organic C (14C-DOC) and in the microbial biomass C (14C
      MBC)], and ranged from 0.96 to 8.10 mg x kg(-1) and 1.70 to 49.16 mg x kg(-1),
      respectively. The proportion of 14C-SOC in SOC was 0.09%-0.64%. The 14C-DOC /DOC
      and 14C-MBC /MBC were 5.07%- 4.3% and 2.51%-13.12%, respectively. Thus, the
      distribution and transformation of microbially fixed C had a larger influence on
      the dynamics of DOC and MBC than on the total SOC dynamics. Moreover, the
      abundance of soil bacteria cbbL gene and RubisCO activity were in the range of
      2.40 x 10(7) - 1.9 x 10(8) copies x g(-1) and 34.06-71.86 nmol x (g x min)(-1),
      respectively. The 14C-SOC content was significantly correlated with both the 14C
      MBC content (P < 0.01) and the RubisCO activity (P < 0.01) in all tested soils.
      We concluded that autotrophic CO2 assimilation by soil microbes is significant to
      the global C cycle.

PMID- 24881410
TI  - [Dynamics of microbes and enzyme activities during litter decomposition of Pinus
      massoniana forest in mid-subtropical area].
AB  - The dynamics of microbial quantity and enzyme activities during decomposition
      process of masson pine (Pinus massoniana) leaf litter, oak (Quercus aliena) leaf
      litter and their mixture (at natural mass ratio, 8: 2) were studied with
      litterbag method in the pinus forest typical vegetations of mid-subtropical
      Jinyun Mountain nature reserve. The results showed that the decomposition
      constant K of leaf litter ranked as follows: mixture (0.94) > oak (0.86) > masson
      pine (0.67). Microbial groups and enzyme activity exhibited some similar
      responses to the litter decomposition process. After 135 days, fungal and
      microbial quantities reached the maximum while bacterial and actinomycetic number
      reached the minimum, presumably due to the high-temperature environment. The
      correlative analysis showed that the cellulase and acid phosphatase activity had
      significant positive relationship with the dry weight remaining rate (P < 0.05),
      which played a key role for microbes in utilizing the substrates at early stages.
      Meanwhile, the polyphenol oxidase activity showed highly significant negative
      correlation with the dry weight remaining rate (P < 0.01) in pine litter and the
      mixed litter, which worked on further decay of recalcitrant compound at late
      stages. Through the whole process, the microbial quantity and polyphenol oxidase
      activity were generally in the order of oak litter > mixed litter > pine litter,
      while in most cases the oak litter showed the lowest acid phosphatase activity,
      the ranking of which had some differences with the order of the decomposition
      constant K, indicating that litter decomposition was the result of integrated
      action by microbe and many kinds of enzymes. The results suggested that
      differences in litter composition and seasonal climate strongly influenced the
      microbial communities and the ecosystem processes they mediate. When mixed with
      oak leaves in given stand, the pine litter had an accelerating decomposition
      rate, which might depend on the higher microbial quantity and polyphenol oxidase
      activity in the mixed litter.

PMID- 24881411
TI  - [Levels and possible sources of organochlorine pesticides (OCPs) in camphor
      (Cinnamomum camphora) tree bark from Southern Jiangsu, China].
AB  - Thirty-three camphor tree bark samples were collected from Southern Jiangsu in
      August 2012. They were analyzed for organochlorine pesticides (OCPs), including
      hexachlorobenzene (HCB), DDTs (o,p'-DDE, p,p'-DDE, o,p'-DDD, p,p'-DDD, o,p'-DDT
      and p,p'-DDT), trans-chlordane and cis-chlordane. The concentrations of HCB,
      sigma6 DDTs and sigma Chlordanes ranged (dw) from 0.31 ng x g(-1) to 1.81 ng x g(
      1), 0.40 ng x g(-1) to 17.3 ng x g(-1) and n. d. to 1.03 ng x g(-1),
      respectively. Due to the high volatility, the spatial distribution of HCB in
      Southern Jiangsu was uniform. Compared to the other results, the HCB
      concentration in Southern Jiangsu was lower. The historical usage of technical
      DDT mixture and the dicofol-type DDT were the major sources of DDTs in southern
      Jiangsu. The TC/CC ratio is usually used to distinguish between aged and fresh
      chlordane. According to the ratio of TC/CC, the chlordane in the urban area was
      derived from the fresh application of technical chlordane, and that in the rural
      area was attributed to the historical usage.

PMID- 24881412
TI  - [Combined stress of enhanced UV-B radiation and 1,2,4-trichlorobenzene
      contamination on the growth of green vegetable].
AB  - A pot experiment was conducted to study the effects of UV-B radiation enhancement
      alone, 1,2,4-trichlorobenzene (TCB) contamination soil alone, and the combined
      stress on the growing process, stomatal resistance and leaf structure of green
      vegetable. The results showed that 1,2,4-TCB contamination alone had more
      significant inhibitory effect on the growth of green vegetable than the combined
      stress. Both UV-B radiation enhancement and 1,2,4-TCB contamination reduced the
      stomatal resistance of front and reverse leaves. Enhanced UV-B radiation resulted
      in the albino of leaves. 1,2,4-TCB contamination resulted in the fading of leaf
      color and the appearing of black spots on leaf surfaces, and the enhanced UV-B
      radiation strengthened the black-spot symptom. In conclusion, the effects of UV-B
      radiation enhancement alone, 1,2,4-trichlorobenzene (TCB) contamination soil
      alone and the combined stress on the growth indicators of green vegetable were
      different.

PMID- 24881413
TI  - [Effect of ectomycorrhizae on heavy metals sequestration by thermostable protein
      in rhizosphere of Pinus tabulaeformis under Cu and Cd stress].
AB  - Copper and cadmium in soil is a severe soil pollution problem in China. It is
      effective to remediate the soil by sequestrating Cu and Cd with tolerant plant
      and microorganism. Ectomycorrhizae could exude a large number of organic matter
      to reduce the biological effectiveness of heavy metals. Therefore, under Cu or Cd
      stress, thermostable protein in rhizosphere exuded by roots of pine seedling
      (Pinus tabulaeformis) associated with ectomycorrhizal fungi (Xerocomus
      chrysenteron) can have the potential of sequestration for heavy metals. The
      results illustrated that the association didn't impact on exudation of
      thermostable protein but treated with different concentrations of Cu, the total
      thermostable protein (TTP) and easily extracted thermostable protein (EETP) in
      mycorrhizal rhizosphere increased by 2.64 to 11.79 times compared with non
      mycorrhizal one. While treated with Cd, it was 1.49 to 7.56 times. Further
      analysis of metal content in rhizosphere showed that association significantly
      increased the Cu sequestration in mycorrhizal rhizosphere where relative content
      of Cu was 1.81 to 2.75 times higher than those in non-mycorrhizal rhizosphere
      while most of Cu was sequestrated by thermostable protein, 4.19 to 43.00 times
      higher in protein than in root cell. Meanwhile results of Cd treatments showed a
      similar trend with Cu treatments. That indicated that under excessive heavy
      metals stress, ectomycorrhizal association facilitated the exudation of
      thermostable protein so as to extend the capacity of sequestration for excessive
      heavy metals and mitigate the phytotoxicity from heavy metals polluted soil.

PMID- 24881414
TI  - [Isolation and characterization of a halotolerant p-nitroaniline degrading strain
      S8].
AB  - A bacterial strain S8 was isolated from pesticide-contaminated sludge, which
      showed ability of utilizing p-nitroaniline as the sole source of carbon and
      nitrogen for growth. Based on the morphology, the physiological and biochemical
      characteristics, and the 16S rDNA sequence analysis, the strain was identified as
      Bacillus subtilis. Strain S8 showed high efficiency in p-nitroaniline
      degradation. 65.6% and 55.8% of p-nitroaniline (60 mg x L(-1) and 120 mg x L(-1))
      were degraded by this strain within 72 hours under the optimal conditions of
      31degrees C and pH 6.0. Besides, strain S8 degraded 49.5% p-nitroaniline in 7%
      NaCl and 27.4% p-nitroaniline in 10% NaCl (72 h), which showed that the strain S8
      had a high salinity tolerance. When the LC-MS method was used for identification
      of the biodegradation products, six kinds of degradation products were found, two
      of which were identified as phenol and hydroquinone. To date, this is the first
      report on the degradation of p-nitroaniline by Bacillus subtilis. These results
      suggest that S8 could be a potential candidate for treating p-nitroaniline
      contaminated saline wastewater.

PMID- 24881415
TI  - [Optimized cultivation of a bioflocculant M-C11 produced by Klebsiella pneumoniae
      and its application in sludge dewatering].
AB  - A bioflocculant-producing Klebsiella pneumoniae strain C11 was screened out from
      activated sludge and the optimal medium conditions for the production of
      microbial flocculant M-C11 were determined. The bioflocculant was used in
      activated sludge dewatering and compared with conventional chemical conditioners.
      Effects of pH, CaCl2 dosages and M-C11 dosages on sludge dewaterability were
      investigated. The optimized conditions for M-C11 production indicated that the
      optimal medium carbon, nitrogen, metal ion were 30 g x L(-1) glucose, 2 g x L(-1)
      NaNO3 and 0.5 g x L(-1) MgSO4, respectively. The flocculating rate with kaolin
      suspension was as high as 91.70%, when incubated in a rotary shaker at 150 r x
      min(-1) and 37 degrees C for 48 h. The microbial focculant showed excellent pH
      and thermal stability over a pH range of 4-8 and a temperature range of 20-60
      degrees C. Then the bioflocculant M-C11 produced by Klebsiella pneumoniae was
      employed to enhance the sludge dewaterability. The sludge resistance to
      filtration (SRF) and cake moisture decreased from 11.64 x 10(12) m x kg(-1) and
      98.86% to 4.66 x 10(12) m x kg(-1) and 83.74%, respectively. Sludge dewatering
      performance was more significantly improved with the optimal conditioning dosages
      (pH = 6, 3 mL M-C11, 4 mL CaCl2), than inorganic flocculating reagents such as
      aluminum sulfate and polymeric aluminum chloride (PAC). The microbial flocculant
      has advantages over traditional sludge conditioners for its lower cost, benign
      biodegradability and ignorable secondary pollution. In addition, it was favorably
      adapted to the sludge pH and salinity. The novel bioflocculant could be used as a
      potential conditioner for sludge dewatering.

PMID- 24881416
TI  - [Speciation analysis of lead losses from anthropogenic flow in China].
AB  - Lead pollutants in the environment origin from lead losses in the anthropogenic
      lead cycle, and the diversity of lead loss species indicates different starting
      points for transferring and transformation in the environmental medium. The
      knowledge of lead lose species from anthropogenic flow can help lay a scientific
      and sound foundation for future environmental risk assessment and source
      management. The anthropogenic lead flow was tracked down in the research, and
      with the methodology of physical and chemical analysis, the species of lead
      losses in all life-cycle stages were recognized. The year 2010 was used as a case
      study for quantitative speciation analysis of total lead losses. It turns out
      that PbSO4 is most, which contributes 23.4% of the total losses; followed by PbO,
      Pb and PbCO3, and these three species together occupy 46.2%. In addition, for
      every 1 kt refined lead consumed domestically, lead losses total 547.9 t, of
      which 73.3% are from use and waste management & recycling. In view of speciation,
      PbSO4 is 128.2 t and mainly occurs in production and waste management &
      recycling; while most PbO, Pb and PbCO3 are separately from waste management &
      recycling, use and production.

PMID- 24881417
TI  - [Establishment and application of pollutant discharge-environment quality model].
AB  - In order to explore the mutual influence between pollutant discharge and
      environment quality, relation models of pollutant discharge and environmental
      quality were established, and the relationship was divided into four types, low
      pollutant discharge-high environmental quality, high pollutant discharge-high
      environmental quality, high pollutant discharge-low environmental quality, and
      low pollutant discharge-low environmental quality. The evolution paths from one
      type into another were also discussed. The regional data in 2005 and 2010 was
      used to validate the pollutant discharge-environmental quality models. The
      results showed that most regions of China belonged to the high pollutant
      discharge-low environmental quality type, and the pollutant discharge-
      environmental quality type didn't vary too much during the 2005-2010 period. In
      the majority of provinces, the environmental quality index was higher than the
      pollutant discharge index, and the pollutant discharge quantity overflowed the
      environmental capacity. The reduction of pollutant discharge quantity should be
      the most important environmental problem in China. At present, China is in a
      critical period of environmental governance, and excessive disturbance from
      economic system to the environment system should be prevented. The results should
      be helpful for understanding the regional environmental quality situation, on the
      implementation of pollutant discharge reduction, and the improvement of
      environmental quality.

PMID- 24881418
TI  - [Advances in the pathway and molecular mechanism for the biodegradation of
      microcystins].
AB  - With increasing discharge of wastewater containing nitrogen and phosphorus into
      rivers and lakes, harmful cyanobacterial blooms have become more frequent
      worldwide. The main harm of cyanobacterial blooms is producing and releasing a
      great amount of algal toxins mainly containing microcystins (MCs). Since MCs are
      extremely harmful to plants and animals and difficult to be removed efficiently
      by the traditional processing methods, how to control harmful cyanobacterial
      blooms and remove MCs have become an unsolved problem in the field of
      environmental science all over the world. This paper summarized the structure and
      toxicity of MCs, the MCs-biodegrading bacterial strains, the enzymes, the genes,
      and the biodegradation pathway and molecular mechanism of MCs. The further
      research subjects were also proposed. It was hoped that this review could provide
      a reference for restoring MCs-polluted lakes and reservoirs and ensuring drinking
      water safety.

PMID- 24881419
TI  - The diagnosis and management of psychogenic non-epileptic seizures in the UK
      Armed Forces.
AB  - Psychogenic non-epileptic seizures (PNES) is a disorder that mimics epilepsy, but
      does not have the associated organic changes or abnormal neuronal discharge foci
      in the brain. In this article the diagnosis, management and clinical
      considerations of managing this condition in the UK Armed Forces are considered.
      The occupational and operational considerations for the military environment are
      also discussed.

PMID- 24881420
TI  - Anterior cruciate ligament injury in Royal Marine basic training.

PMID- 24881421
TI  - Does the method of aeromedical evacuation from the point of wounding to a field
      hospital have an effect on subsequent blood product usage and patient physiology?

PMID- 24881422
TI  - The principles of managing open fractures.
AB  - Any fracture of a bone which communicates with the outside environment via a
      wound in the skin is classified as an open fracture. This may be from penetration
      by sharp objects from the exterior, laceration caused by the fracture fragments,
      or shearing forces that tear or de-glove soft tissue from a limb. These injuries
      vary in mechanism and severity, ranging from a broken finger caught in a bulkhead
      door to a catastrophic lower limb fracture suffered from an improvised explosive
      device (IED). We address the management principles that can be applied to all
      open fractures regardless of cause.

PMID- 24881423
TI  - The acutely swollen knee. Part 1: Management of atraumatic pathology.
AB  - The acutely swollen knee is a common presentation of knee pathology in the
      Emergency Department and the primary care setting whether on board ship, a
      Regimental Aid Post or Medical Centre. The swollen knee has both traumatic and
      atraumatic (systemic) causes, all of which can be accurately diagnosed with an
      understanding of the underlying injury patterns and patho-anatomy. In Part One,
      we will be examining the management of non-traumatic causes, followed by Part
      Two, looking at traumatic causes, in the next issue of the Journal. A detailed
      clinical history combined with thorough clinical examination will establish the
      diagnosis, or at least the narrow differential diagnosis in the majority of
      cases. The uses of specialist examination techniques, diagnostic imaging and
      arthrocentesis can further assist the clinician in confirming the correct
      diagnosis and thus prescribing the appropriate treatment. This review will
      endeavour to give a consensus of opinion and structured guidelines in the
      diagnosis and initial management of patients presenting with acute or recent
      onset swelling of the knee related to atraumatic pathology.

PMID- 24881424
TI  - Intraosseous access in the military operational setting.
AB  - INTRODUCTION: In an operational military environment, circulatory access can
      prove difficult for a variety of reasons including profound hypovolaemia, and
      limited first responder experience. With many injuries that cause catastrophic
      haemorrhage, such as traumatic limb amputations, circulatory access is needed as
      quickly as possible. Since 2006, the Defence Medical Services have been using the
      EZ-IO and FAST1 devices as a means of obtaining circulatory access. METHODS: A
      prospective observational study was conducted between March and July 2011 at the
      Emergency Department, Camp Bastion, Afghanistan. All patients with an
      intraosseous device had data recorded that included if the device successfully
      flushed (functionality) and if any problems were encountered. RESULTS: 117
      patients presented with a total of 195 devices: 149 were EZ-IO (76%) and 46 were
      FAST1 (24%). Functionality was recorded for 111 (57%), with 17 failing to
      function, yielding an overall success rate of 84.7%. Device failure was observed
      to be more prevalent in the humerus; inability to flush the device was the
      leading cause, followed by mechanical failure. There were 2 complications, device
      breaking on removal being the reason for both. CONCLUSIONS: The devices in the
      study were tested for a period of time following insertion (median 32 minutes),
      and still the success rates mirror those found in the literature. Observed
      differences between sites were not found to be significant with confidence
      intervals overlapping. Further work is proposed to investigate the long-term
      complications of intraosseous devices.

PMID- 24881425
TI  - Contingency: the likely spectrum of injuries based upon a review of three recent
      undeveloped theatres of operations--CORPORATE, TELIC 1 and HERRICK 4.
AB  - Contingency operations are by their nature unpredictable and high-risk, with
      undeveloped logistical support, and medical provision is no exception. Can the
      contingency experiences of the last three decades help to predict the type of
      casualties that may be seen in future contingency operations? By reviewing
      published casualty statistics available from Operations CORPORATE, TELIC 1 and
      HERRICK 4 it can be demonstrated, unsurprisingly, that gunshot wounds and blast
      injuries dominate battle injuries, but that disease non-battle injuries also
      constitute a significant draw on medical provision, particularly gastrointestinal
      illness in hot environments. Planning for medical support for future contingency
      operations should anticipate this. Disease non-battle injuries have the potential
      to render a large proportion of a force combat-ineffective, requiring
      preventative measures to avoid overwhelming the available medical facilities.
      When operations occur in populated areas civilian casualties are likely to pose
      difficulties to medical support, due to issues with onward evacuation and a wider
      case mix, such as paediatrics.

PMID- 24881426
TI  - Red Alert: diagnosis and management of the acute red eye.
AB  - The acute red eye represents a broad spectrum of disease encompassing benign self
      limiting conditions to potentially vision-threatening ophthalmic or system
      disease. This article will review clinical principles essential for the diagnosis
      and treatment of red eye relevant to all Armed Forces primary care and emergency
      medicine practitioners.

PMID- 24881427
TI  - Infective skin conditions in an adult sea-going population.
AB  - Infective skin conditions represent a significant element of the caseload for sea
      going and shore-side clinicians. They are common within the wider military
      setting due to the frequent requirement to live in close proximity to others in
      conditions which favour the spread of skin and soft tissue infections (SSTI).
      Within the UK civilian population, 24% of individuals see their family doctor for
      skin conditions each year, accounting for 13 million primary care consultations
      annually. Of these, almost 900,000 were referred to dermatologists in England in
      2009-2010 and resulted in 2.74 million secondary care consultations. Several
      recent articles have highlighted the problem of Panton-Valentine Leukocidin
      Staphylococcus aureus (PVL-SA) infection and carriage in sailors on submarines,
      and soldiers deployed to Afghanistan. However, the majority of published articles
      relate to land-based military personnel. This article aims to provide an overview
      of the most common infective skin conditions presenting among Naval personnel
      (based on the authors' experience), illustrated by several case studies, together
      with an approach to their diagnosis and management.

PMID- 24881428
TI  - Sport-related eye trauma.
AB  - Sport-related eye injuries are a common cause of acute ocular injury. This
      article provides a basic clinical overview of the diagnosis and immediate medical
      management of sport-related eye injuries, and is relevant to all Armed Forces
      primary care and emergency medicine practitioners.

PMID- 24881429
TI  - Concussion: no longer a laughing matter in sport.

PMID- 24881431
TI  - Improving health through physical activity, and its importance for the Royal
      Navy.

PMID- 24881430
TI  - Athletic altitude training protocols and their application in preparation for
      mountainous operations.
AB  - In recent years, small scale counter-insurgency and expeditionary operations have
      frequently taken place in mountainous, high-altitude areas. Preparation of
      soldiers for these environments has typically focussed on extended stays at
      altitude to ensure physiological acclimatisation. However, with the likelihood
      that future UK deployments may be unpredictable and thus with little time for
      preparation, is there a means by which the same acclimatisation may be achieved?
      The field of athletics has been researching such adaptations since the rise of
      the elite North African long-distance runners in the 1960s. These athletes all
      lived high above sea level and had become accustomed to performing in the
      relatively hypoxic environment found at high altitudes. The research has focussed
      on eliciting physiological acclimatisation in as short a time as possible, while
      maintaining the ability to train at the correct intensity. In the following
      review of altitude training we highlight areas for future investigation and
      assess whether protocols developed for athletes can be applied to military
      personnel.

PMID- 24881433
TI  - Operation PATWIN: HMS DARING's experience of providing humanitarian disaster
      relief following super-Typhoon Haiyan.
AB  - Super-Typhoon Haiyan struck the Philippines on 7 November 2013. The initial
      reports estimated 10 000 fatalities and four million displaced persons. As the
      United Kingdom's initial response to this disaster, HMS DARING was diverted from
      her deployment to take part in humanitarian aid, named Operation PATWIN. This
      article will outline the medical aspects of the relief effort undertaken and aim
      to identify any lessons that may inform future operations.

PMID- 24881432
TI  - The impact of traumatic pelvic fractures on sporting activity and quality of
      life.
AB  - BACKGROUND: Pelvic fractures (PFX) reflect high-energy trauma with high mortality
      and morbidity. AIM: We attempted to determine: whether there is a decrease in
      levels of sporting and physical activity in patients with operatively-treated
      PFX; risk factors for decreased sporting activity; any correlation between
      sporting activity and quality of life in this group. METHODS: Retrospective
      demographics on mechanism of injury, fracture type, associated injury and injury
      severity score, as well as prospective documentation of the level and frequency
      of sporting activity, were collected from adult patients treated operatively for
      a PFX between 2007 and 2010, using a specifically designed questionnaire. Quality
      of life before and after injury was also recorded using the EuroQol-5D health
      outcome tool. RESULTS: 80 patients without pre-existing musculoskeletal
      disability were enrolled. The mean age was 44.9 years (18-65). The mean follow-up
      was 30.5 months (12-39). A decrease in level and frequency of sporting activity
      was observed. It was associated with lower-extremity associated injuries, but not
      with injury severity score, PFX severity, PFX type, age, or timing of follow-up.
      Sporting activity before injury predicted higher levels of sporting participation
      after injury. Decreased sporting activity after injury was associated with
      decreased EuroQol-SD score. CONCLUSIONS: Patients should be counselled on the
      likelihood of a reduction in sporting activities after surgically treated PFX. A
      larger multi-centre study is needed to further expand on the evidence of the true
      impact of PFX and its associated injuries on sporting activity.

PMID- 24881434
TI  - The emergence of vascular surgery as a separate specialty: implications for the
      military.
AB  - Vascular surgery is evolving from being a sub-specialty of general surgery to
      becoming a separate surgical specialty. This will have implications in terms of
      the training, skill-set and workload of surgeons working in the NHS. There are
      implications for the military too, as a deploying trauma team must have both
      general and vascular surgical capabilities. This article explores the reasons for
      the changes occurring and discusses the wider implications.

PMID- 24881435
TI  - The new NEMOs--changes to initial medical officer training.
AB  - It is desirable that a Royal Navy Medical Officer is not only medically competent
      but also a proficient Naval Officer with an ethos common to all Officers,
      irrespective of specialty or branch. In 2012 Britannia Royal Naval College
      (BRNC), in conjunction with the Institute of Naval Medicine (INM), modified the
      New Entry Medical Officer (NEMO) training course to comprise an initial phase at
      BRNC (15 weeks) followed by a second phase at INM (16 weeks). This is in contrast
      to the traditional training delivered at INM and Fort Blockhouse prior to joining
      BRNC for 7 weeks. The following article is a reflection of this experience.

PMID- 24881436
TI  - Diploma in Retrieval and Transfer Medicine.

PMID- 24881437
TI  - The proposed use of Defence Medical Information Capability Programme (DMICP)
      templates to improve patient care in the joint environment.

PMID- 24881438
TI  - The sun sets over the Defence Medical Services Training Group Keogh Barracks for
      the last time.

PMID- 24881439
TI  - Presidential speech December 28, 2013.

PMID- 24881440
TI  - The year ahead.

PMID- 24881441
TI  - Management of complications of dental implant surgery.

PMID- 24881442
TI  - Complications in implant dentistry.
AB  - The mainstream use of dental implants has allowed millions of patients to benefit
      from the predictability of dental implant therapy and, in many instances, dental
      implants have become the standard of care. Even though success rates in implant
      dentistry are well above 90 percent, complications do occur. Most complications
      are preventable with proper planning and execution. Others are inherent to the
      risks of surgery and may require intervention. The purpose of this paper is to
      classify the possible complications that may occur and to discuss their
      prevention and management.

PMID- 24881443
TI  - Part II. Minimizing alveolar bone loss during and after extractions. Protocol and
      techniques for alveolar bone preservation.
AB  - Alveolar ridge resorption accelerates following extraction of teeth and the
      residual defect varies from socket to socket. This article proposes a new
      treatment oriented classification of extraction defects. It also reviews several
      graft materials and membranes that aid in the decision for selecting an
      appropriate socket preservation technique. The algorithm developed by the authors
      helps design a potentially successful treatment plan based on the classification
      of extraction defects, with choices ranging from no treatment to complex grafting
      procedures (i.e. allogenic block grafts). In addition, the principles of wound
      healing and the ideal time points for utilizing the various types of graft
      materials and implants are discussed. This socket preservation treatment
      algorithm will guide clinicians to employ surgical procedures using various
      biomaterials to promote a successful outcome.

PMID- 24881444
TI  - CAD/CAM guided surgery in implant dentistry: a brief review.
AB  - Advanced imaging and CAD/CAM technologies and their applications in enhancing
      treatment outcomes in implant dentistry have gained widespread interest. Guided
      implant surgery utilizing these advanced technologies has significant
      applications in implant dentistry. This article provides information on some of
      the perceived advantages and disadvantages for planning guided versus
      conventional implant surgery as well as basic steps involved in the fabrication
      of guided surgical templates (GST).

PMID- 24881445
TI  - CAD/CAM guided surgery in implant dentistry. A review of software packages and
      step-by-step protocols for planning surgical guides.
AB  - Three-dimensional radiographic imaging for dental implant treatment planning is
      gaining widespread interest and popularity. However, application of the data from
      30 imaging can be a complex and daunting process initially. The purpose of this
      article is to describe features of three software packages and the respective
      computerized guided surgical templates (GST) fabricated from them. A step-by-step
      method of interpreting and ordering a GST to simplify the process of the surgical
      planning and implant placement is discussed.

PMID- 24881446
TI  - How to avoid litigation with dental implant patients.

PMID- 24881447
TI  - AO Dental Fraternity names the 2013 Trudi Birger Award recipients.

PMID- 24881448
TI  - Why convention?

PMID- 24881449
TI  - Changing of the guard at the Hebrew University-Hadassah School of Dental Medicine
      founded by the Alpha Omega International Dental Fraternity.

PMID- 24881450
TI  - Guest editorial.

PMID- 24881451
TI  - Account: characterization and identification of microcystins by mass
      spectrometry.
AB  - In this brief overview, the authors describe mass spectral techniques for the
      detection and identification of microcystin toxins. Microcystins are secondary
      metabolites produced by cyanobacteria. Determination of these toxic compounds and
      discovery of new variants is very important as they pose a great danger to the
      human food chain. Cyanobacterial blooms frequently occur in many areas worldwide
      and have the potential to contaminate the water via cyanotoxin release,
      especially microcystins. Among the various analytical techniques used for
      analysis, mass spectrometry has become the most important method as it allows
      simultaneous quantification and structural characterization of multiple
      microcystin variants. This brief overview article focuses on mass spectrometry
      techniques for identification of microcystins, including ionization methods, mass
      spectral fragmentation routes, profiling techniques, tandem and high-resolution
      mass spectrometry as well as typing of cyanobacterial strains.

PMID- 24881452
TI  - Characterisation of an inexpensive sonic spray ionisation source using laser
      induced fluorescence imaging and mass spectrometry.
AB  - A commercially available airbrush gun as a new source for spray ionisation is
      presented. It is best operated employing moderate stagnation pressures, resulting
      in a sonic gas flow. A mass spectrometric investigation on the amino acid Lysine
      and several peptides reveals that this inexpensive approach results in
      reproducible mass spectra. The ion patterns strongly resemble the results from
      other studies obtained with custom-made sonic spray vaporisers. The patterns also
      resemble the mass spectra recorded with electrospray devices. For a better
      understanding of the vaporisation process, the mass spectrometry experiments are
      accompanied by laser-induced fluorescence experiments. Inverse Abel Transform of
      the obtained fluorescence maps allows the determination of the full three
      dimensional distribution of the spray cone. Furthermore, via exploitation of the
      solvatochromism of the used dye the solvation-state distribution can be
      visualised. In addition, expansion parameters, such as droplet size and velocity,
      are obtained by laser stroboscopy. The experiments demonstrate that the analyte
      hardly desolvates throughout the expansion. This indicates a subsequent
      vaporisation of the residual solvent in the intermediate pressure region of the
      mass spectrometer.

PMID- 24881454
TI  - Studying ultra-complex crude oil mixtures by using high-field asymmetric waveform
      ion mobility spectrometry (FAIMS) coupled to an electrospray ionisation-LTQ
      orbitrap mass spectrometer.
AB  - High-field asymmetric waveform ion mobility spectrometry (FAIMS) was coupled
      directly to an LTQ Orbitrap mass spectrometer to analyze a nitrogen-rich crude
      oil. Analyzing crude oil is extremely difficult because of the complexity, as up
      to 100,000 different components can be present. Therefore, simplification of
      crude oil increases the information content because discrimination and
      suppression effects are reduced. Here, the first results are presented that show
      that FAIMS can be an important tool for the simplification of complex mixtures.
      Additionally, the results show that FAIMS is an excellent tool that allows not
      only a simplification of such complex mixtures, but also shows the separation of
      isomeric compounds that have the same elemental composition but different
      structure and conformation.

PMID- 24881453
TI  - Analysis of organic aerosols using a micro-orifice volatilization impactor
      coupled to an atmospheric-pressure chemical ionization mass spectrometer.
AB  - We present the development and characterization of a combination of a micro
      orifice volatilization impactor (MOVI) and an ion trap mass spectrometer (IT/MS)
      with an atmospheric-pressure chemical ionization (APCI) source. The MOVI is a
      multi-jet impactor with 100 nozzles, allowing the collection of aerosol particles
      by inertial impaction on a deposition plate. The pressure drop behind the nozzles
      is approximately 5%, resulting in a pressure of 96kPa on the collection surface
      for ambient pressures of 101.3 kPa. The cut-point diameter (diameter of 50%
      collection efficiency) is at 0.13 microm for a sampling flow rate of 10 L min(
      1). After the collection step, aerosol particles are evaporated by heating the
      impaction surface and transferred into the APCI-IT/MS for detection of the
      analytes. APCI was used in the negative ion mode to detect predominantly mono-
      and dicarboxylic acids, which are major oxidation products of biogenic terpenes.
      The MOVI-APCI-IT/MS instrument was used for the analysis of laboratory-generated
      secondary organic aerosol (SOA), which was generated by ozonolysis of alpha
      pinene in a 100 L continuous-flow reactor under dark and dry conditions. The
      combination of the MOVI with an APCI-IT/MS improved the detection Limits for
      small dicarboxylic acids, such as pinic acid, compared to online measurements by
      APCI-IT/MS. The Limits of detection and quantification for pinic acid were
      determined by external calibration to 4.4 ng and 13.2 ng, respectively. During a
      field campaign in the southern Rocky Mountains (USA) in summer 2011 (BEACHON
      RoMBAS), the MOVI-APCI-IT/MS was applied for the analysis of ambient organic
      aerosols and the quantification of individual biogenic SOA marker compounds.
      Based on a measurement frequency of approximately 5 h, a diurnal cycle for pinic
      acid in the sampled aerosol particles was found with maximum concentrations at
      night (median: 10.1 ngm(-3)) and minimum concentrations during the day (median:
      8.2 ng m(-3)), which is likely due to the partitioning behavior of pinic acid and
      the changing phase state of the organic aerosol particles with changing relative
      humidity.

PMID- 24881455
TI  - Unidirectional triple hydrogen rearrangement in the radical cations of electron
      rich 3-aryl-1-propanols: further evidence and limitation.
AB  - The unidirectional triple-hydrogen (3H) rearrangement of the radical cations of 3
      aryl-1-propanols bearing an electron-rich substitutent in the para-position was
      investigated for the diastereomeric 2-(4-dimethylamino)benzylcyclohexanols and 2
      (4-dimethylamino)-benzylcyclopentanols and confirmed to be a highly
      stereospecific feature. Whereas the standard electron ionization (EI) (70 eV)
      mass spectra of the trans-isomers exhibit very minor (approximately 2%-3%) albeit
      stereospecific peaks for the relevant C8H13N*+ ions (m/z 123), the metastable ion
      [mass-analyzed ion kinetic energy (MIKE)] spectra show these peaks with
      significant relative intensity (8%-17%). The respective cis-isomers do not
      undergo the 3H rearrangement, be it under standard or under metastable-ion
      conditions. The stereospecific 3H rearrangement is suppressed in the radical
      cations of cis- and trans-3-(4-dimethylamino)phenylcyclohexanol, the mass and
      MIKE spectra of which are governed by cleavage processes of the cyclohexane ring,
      which impedes the stereochemical assignment of the isomers by mass spectrometry.
      A multistep mechanism for the unidirectional 3H rearrangement is discussed in
      view of the present and previous experimental data.

PMID- 24881456
TI  - Determination of site selectivity of different carcinogens for preferential
      mutational hot spots in oligonucleotide fragments by ion-pair reversed-phase nano
      liquid chromatography tandem mass spectrometry.
AB  - Ion-pair reversed-phase nano liquid chromatography coupled with nanospray ion
      trap mass spectrometry was used to investigate site selectivity of the known
      carcinogens N-acetoxy-2-acetylaminofluorene, N-hydroxy-4-aminobiphenyl and (+/-)
      anti-benzo[a]pyrene diol epoxide with the synthetic double-strand 14-mer long
      oligonucleotide fragment of the p53 gene containing two mutational hot-spot
      codons (5'-P-ACC155 CGC156 GTC157 CGC158 GC/5'-GCG CGG ACG CGG GT). The
      investigation was performed using a monolithic polystyrene divinylbenzene
      capillary column and triethylammonium bicarbonate as an ion-pair reagent. The
      exact location of the carcinogen on the modified oligonucleotide backbone was
      determined using characteristic collision-induced dissociation fragmentation
      patterns obtained under negative-ion mode ionization. In all these cases, the
      adducted, isomeric oligonucleotides formed were chromatographically resolved and
      structural identification was performed without any prior deoxyribonucleic acid
      cleavage or hydrolysis. The knowledge of the site specificity of a carcinogen,
      especially at purported mutational hot spots, is of paramount importance (1) in
      establishing the identity of biomarkers for an early risk assessment of the
      formed DNA adducts, (2) developing repair mechanisms for the formed carcinogen
      adducted DNA, and (3) understanding the nature of the covalent bond formed and
      mapping the frequency of the adduction process.

PMID- 24881457
TI  - Liquid chromatography-high resolution/ high accuracy (tandem) mass spectrometry
      based identification of in vivo generated metabolites of the selective androgen
      receptor modulator ACP-105 for doping control purposes.
AB  - Selective androgen receptor modulators (SARMs) represent an emerging class of
      therapeutics which have been prohibited in sport as anabolic agents according to
      the regulations of the World Anti-Doping Agency (WADA) since 2008. Within the
      past three years, numerous adverse analytical findings with SARMs in routine
      doping control samples have been reported despite missing clinical approval of
      these substances. Hence, preventive doping research concerning the metabolism and
      elimination of new therapeutic entities of the class of SARMs are vital for
      efficient and timely sports drug testing programs as banned compounds are most
      efficiently screened when viable targets (for example, characteristic
      metabolites) are identified. In the present study, the metabolism of ACP-105, a
      novel SARM drug candidate, was studied in vivo in rats. Following oral
      administration, urine samples were collected over a period of seven days and
      analyzed for metabolic products by Liquid chromatography-high resolution/high
      accuracy (tandem) mass spectrometry. Samples were subjected to enzymatic
      hydrolysis prior to liquid-liquid extraction and a total of seven major phase-I
      metabolites were detected, three of which were attributed to monohydroxylated and
      four to bishydroxylated ACP-105. The hydroxylation sites were assigned by means
      of diagnostic product ions and respective dissociation pathways of the analytes
      following positive or negative ionization and collisional activation as well as
      selective chemical derivatization. The identified metabolites were used as target
      compounds to investigate their traceability in a rat elimination urine samples
      study and monohydroxylated and bishydroxylated species were detectable for up to
      four and six days post-administration, respectively.

PMID- 24881458
TI  - Metabolite profiling and fingerprinting of Suillus species (Basidiomycetes) by
      electrospray mass spectrometry.
AB  - The genus Suillus is known for the occurrence of a series of prenylated phenols
      and boviquinones. The extracts of four different Suillus species [S. bovinus, S.
      granulatus, S. tridentinus and S.variegatus) were investigated by using rapid
      ultra-performance Liquid chromatography/electrospray ionization mass spectrometry
      (UPLC/ESI-MS) and direct infusion electrospray ionization Fourier transform ion
      cyclotron resonance mass spectrometry (ESI-FT-ICR-MS). While direct infusion ESI
      FT-ICR mass spectra give a fast overview concerning the elemental compositions of
      the compounds and, therefore, hints to the main metabolites, UPLC/ESI-tandem mass
      spectrometry is shown to be a useful tool for their identification. A principal
      component analysis (PCA) and hierarchical cluster analysis (HCA) based on the
      UPLC/ESI-MS clearly showed that the metabolite profiles can be used not only for
      the identification and classification of such fungi but also as a sophisticated
      and powerful tool for the chemotaxonomy of fungi. Furthermore, a clear
      discrimination of various types of biological samples (fruiting bodies versus
      mycelial cultures) is also possible. The orthogonal partial least squares (OPLS)
      two-class models of both UPLC/ESI-MS and ESI-FT-ICR-MS possess a clear
      differentiation of two compared Suillus species representing the between class
      variation and the within class variation. Based on generated S-plots and Loading
      plots, statistically significant metabolites could be identified as potential
      biomarker for one species.

PMID- 24881459
TI  - Catch me if you can: challenges and applications of cross-linking approaches.
AB  - Biomolecular complexes are the groundwork of life and the basis for cell
      signaling, energy transfer, motion, stability and cellular metabolism.
      Understanding the underlying complex interactions on the molecular level is an
      essential step to obtain a comprehensive insight into cellular and systems
      biology. For the investigation of molecular interactions, various methods,
      including Forster resonance energy transfer, nuclear magnetic resonance
      spectroscopy, X-ray crystallography and yeast two-hybrid screening, can be
      utilized. Nevertheless, the most reliable approach for structural proteomics and
      the identification of novel protein-binding partners is chemical cross-linking.
      The rationale is that upon forming a covalent bond between a protein and its
      interaction partner (protein, lipid, RNA/DNA, carbohydrate) the native complex
      state is "frozen" and accessible for detailed mass spectrometric analysis. In
      this review we provide a synopsis on crosslinker design, chemistry, pitfalls,
      limitations and novel applications in the field, and feature an overview of
      current software applications.

PMID- 24881460
TI  - Probabilistic models for capturing more physicochemical properties on protein
      protein interface.
AB  - Protein-protein interactions play a key role in a multitude of biological
      processes, such as signal transduction, de novo drug design, immune responses,
      and enzymatic activities. It is of great interest to understand how proteins
      interact with each other. The general approach is to explore all possible poses
      and identify near-native ones with the energy function. The key issue here is to
      design an effective energy function, based on various physicochemical properties.
      In this paper, we first identify two new features, the coupled dihedral angles on
      the interfaces and the geometrical information on pi-pi interactions. We study
      these two features through statistical methods: a mixture of bivariate von Mises
      distributions is used to model the correlation of the coupled dihedral angles,
      while a mixture of bivariate normal distributions is used to model the
      orientation of the aromatic rings on pi-pi interactions. Using 6438 complexes, we
      parametrize the joint distribution of each new feature. Then, we propose a novel
      method to construct the energy function for protein-protein interface prediction,
      which includes the new features as well as the existing energy items such as
      dDFIRE energy, side-chain energy, atom contact energy, and amino acid energy.
      Experiments show that our method outperforms the state-of-the-art methods, ZRANK
      and ClusPro. We use the CAPRI evaluation criteria, Irmsd value, and Fnat value.
      On Benchmark v4.0, our method has an average Irmsd value of 3.39 A and Fnat value
      of 62%, which improves upon the average Irmsd value of 3.89 A and Fnat value of
      49% for ZRANK, and the average Irmsd value of 3.99 A and Fnat value of 46% for
      ClusPro. On the CAPRI targets, our method has an average Irmsd value of 3.56 A
      and Fnat value of 42%, which improves upon the average Irmsd value of 4.27 A and
      Fnat value of 39% for ZRANK, the average Irmsd value of 5.15 A and Fnat value of
      30% for ClusPro. 

PMID- 24881461
TI  - Efficacy of azilsartan medoxomil with chlorthalidone in hypertension.
AB  - Azilsartan medoxomil (AZL) is the most recently approved angiotensin receptor
      blocker (ARB) for treating patients with hypertension. A fixed-dose combination
      product with AZL and the thiazide-like diuretic chlorthalidone (CLD) is now
      available to treat individuals who require additional blood pressure lowering.
      For this review, a literature search was conducted using MEDLINE and the keywords
      and MeSH terms azilsartan, azilsartan medoxomil, chlorthalidone, thiazide, blood
      pressure and hypertension. References for retrieved articles were also scanned
      for relevant citations. No language restrictions were used. AZL is structurally
      related to candesartan and has been shown to provide more potent angiotensin
      receptor antagonism versus other ARBs. CLD is a thiazide-like diuretic with a
      longer half-life and greater blood pressure lowering efficacy than
      hydrochlorothiazide. The combination of AZL plus CLD has superior efficacy to
      other ARBs alone or in combination with hydrochlorothiazide based on extensive
      evaluation in clinical trials. This superior efficacy is not offset by a large
      imbalance in clinically important adverse events. 

PMID- 24881462
TI  - Ionic liquid assisted chemical strategy to TiO2 hollow nanocube assemblies with
      surface-fluorination and nitridation and high energy crystal facet exposure for
      enhanced photocatalysis.
AB  - Realization of anionic nonmetal doping and high energy crystal facet exposure in
      TiO2 photocatalysts has been proven to be an effective approach for significantly
      improving their photocatalytic performance. A facile strategy of ionic liquid
      assisted etching chemistry by simply hydrothermally etching hollow TiO2 spheres
      composed of TiO2 nanoparticles with an ionic liquid of 1-butyl-3
      methylimidazolium tetrafluoroborate without any other additives is developed to
      create highly active anatase TiO2 nanocubes and TiO2 nanocube assemblies. With
      this one-pot ionic liquid assisted etching process, the surface-fluorination and
      nitridation and high energy {001} crystal facets exposure can be readily realized
      simultaneously. Compared with the benchmark materials of P25 and TiO2
      nanostructures with other hierarchical architectures of hollow spheres, flaky
      spheres, and spindles synthesized by hydrothermally etching hollow TiO2 spheres
      with nonionic liquid of NH4F, the TiO2 nanocubes and TiO2 nanocube assemblies
      used as efficient photocatalysts show super high photocatalytic activity for
      degradation of methylene blue, methyl orange, and rhodamine B, due to their
      surface-fluorination and nitridation and high energy crystal facet exposure. The
      ionic liquid assisted etching chemistry is facile and robust and may be a general
      strategy for synthesizing other metal oxides with high energy crystal facets and
      surface doping for improving photocatalytic activity. 

PMID- 24881464
TI  - Bioactive compounds from culinary herbs inhibit a molecular target for type 2
      diabetes management, dipeptidyl peptidase IV.
AB  - Greek oregano (Origanum vulgare), marjoram (Origanum majorana), rosemary
      (Rosmarinus officinalis), and Mexican oregano (Lippia graveolens) are
      concentrated sources of bioactive compounds. The aims were to characterize and
      examine extracts from greenhouse-grown or commercially purchased herbs for their
      ability to inhibit dipeptidyl peptidase IV (DPP-IV) and protein tyrosine
      phosphatase 1B (PTP1B), enzymes that play a role in insulin secretion and insulin
      signaling, respectively. Greenhouse herbs contained more polyphenols (302.7-430.1
      MUg of gallic acid equivalents/mg of dry weight of extract (DWE)) and flavonoids
      (370.1-661.4 MUg of rutin equivalents/mg of DWE) compared to the equivalent
      commercial herbs. Greenhouse rosemary, Mexican oregano, and marjoram extracts
      were the best inhibitors of DPP-IV (IC50=16, 29, and 59 MUM, respectively).
      Commercial rosemary, Mexican oregano, and marjoram were the best inhibitors of
      PTP1B (32.4-40.9% at 500 MUM). The phytochemicals eriodictyol, naringenin,
      hispidulin, cirsimaritin, and carnosol were identified by LC-ESI-MS as being
      present in greenhouse-grown Mexican oregano and rosemary. Computational modeling
      indicated that hispidulin, carnosol, and eriodictyol would have the best binding
      affinities for DPP-IV. Biochemically, the best inhibitors of DPP-IV were
      cirsimaritin (IC50=0.43+/-0.07 MUM), hispidulin (IC50=0.49+/-0.06 MUM), and
      naringenin (IC50=2.5+/-0.29 MUM). Overall, herbs contain several flavonoids that
      inhibit DPP-IV and should be investigated further regarding their potential in
      diabetes management.

PMID- 24881466
TI  - Presence of c-kit positive cells in fetal and adult bovine forestomachs.
AB  - The interstitial cells of Cajal (ICC) have been reported to regulate
      gastrointestinal motility. We investigated the distribution and the morphological
      and morphometric characteristics of the immunohistochemical reaction against c
      kit in the forestomachs of fetal, newborn and adult cows. The anti-c-kit reaction
      revealed different populations of ICC among age groups and organs. ICC were more
      numerous and smaller in fetuses. Larger ICC were identified in newborns, except
      for those in the rumen. During the earliest stages of development, ICC were
      abundant in the inner layer of the muscularis and were consistently associated
      with this layer. In all samples, ICC were found in the outer layer of the tunica
      muscularis. ICC were found between the two muscle layers in the omasum at all
      ages; however, they were identified only in the rumen of the adult. Our study
      demonstrated that ICC are present in the forestomach of bovines.

PMID- 24881465
TI  - Counteracting antibiotic resistance: breaking barriers among antibacterial
      strategies.
AB  - INTRODUCTION: To fight against antibiotic resistance, prevention-only is no
      longer an acceptable strategy. The old concept 'one-infection, one-bug, one
      drug', genocentrism in antibiotic discovery, and lack of integration between
      different antimicrobial strategies have probably contributed to current
      weaknesses in confronting antibiotic resistance. Resistance should be combatted
      in all fronts simultaneously, in the patient (complex therapy), the group (where
      resistance is maintained), and the significant environment (polluted by
      resistance). AREAS COVERED: This paper is reviewing why specific 'therapeutic'
      approaches are needed in each of these fronts, using different types of 'drugs'
      directed to a variety of targets, in the goal of inhibiting antibiotic resistant
      bacteria. Multi-target integrated combination strategies and therapies should be
      more extensively evaluated, not only in the infected patient (using novel formats
      for clinical trials), but as associations of 'therapeutic strategies' in the
      different compartments where antibiotic resistance emerges and flows (measuring
      global effects in resistance). EXPERT OPINION: Multi-targeted therapeutic
      approaches require a relaxation of barriers among the various compounds,
      including systemic and topic antibiotics, antiseptics, biocides, anti-resistant
      clones vaccination, phages, decontamination products, and in general eco-evo
      drugs acting on factors influencing ecology and evolution of resistant bacteria.
      The application of methods of systems biology will facilitate such a multi
      lateral attack to antibiotic resistance. Such advances should be paralleled by a
      simultaneous progress in regulatory sciences and close coordination among all
      stakeholders.

PMID- 24881467
TI  - The relationship between socio-economic inequalities, intimate partner violence
      and economic abuse: a national study of women in the Philippines.
AB  - Economic abuse against women has for too long remained a relatively 'unseen' part
      of interpersonal violence, in spite of intimate partner violence (IPV) being a
      public health problem. Most studies on economic abuse derive especially from the
      USA and amongst women in shelters, and their findings are not easily
      generalisable to low-middle-income countries. Socio-economic inequalities render
      women vulnerable to control and risk of abuse. We investigated the role of socio
      economic inequalities in the association between IPV and economic abuse. Logistic
      regression analyses were performed on cross-sectional data from a nationally
      representative sample of 8478 women aged 15-49 years in the 2008 Philippines
      Demographic and Health Surveys. Results indicated strong positive associations
      between both physical IPV and emotional IPV and all four forms of economic abuse.
      Measures of socio-economic inequalities and other covariates such as no
      education, primary education, unemployment and justifying wife beating were also
      statistically significant. Findings suggest the increased need for health care
      practitioners to include economic abuse during the assessment of and response to
      IPV, the implementation of a multidimensional approach to providing tangible
      support and women-centred responses in reported cases of economic abuse, as well
      as measures that enhance socio-economic equality and increase economic
      opportunities for women. 

PMID- 24881468
TI  - Carcinoid tumor on cystic ovarian teratoma.

PMID- 24881469
TI  - Does ultrasonographic measurement of the inferior vena cava diameter correlate
      with central venous pressure in the assessment of intravascular volume in
      patients undergoing gastrointestinal surgery?
AB  - BACKGROUND: Ultrasonography has been suggested as a useful noninvasive tool for
      the detection of hypovolemia in critically ill patients. Hypovolemia after
      preoperative fasting and bowel preparation may compromise hemodynamic function
      during gastrointestinal surgery. However, there are few data comparing
      ultrasonographic examination of the inferior vena cava (IVC) diameter with
      central venous pressure (CVP) measurement in patients undergoing gastrointestinal
      surgery in the assessment of intravascular volume status. MATERIALS AND METHODS:
      Forty American Society of Anesthesiologists I-II patients who underwent elective
      gastrointestinal surgery and 32 healthy volunteers were enrolled in the study.
      The IVC diameters, both during expiration (IVCe) and inspiration (IVCi), and
      right ventricle (RV) were measured with ultrasonography in patients both before
      and after fluid resuscitation. Volunteers were also measured during the time they
      participated in the study. RESULTS: Forty patients (mean age 51 y; 45% female)
      and 32 volunteers (mean age 46 y; 44% female) underwent IVC and RV sonographic
      measurements. The diameters of the IVCe, IVCi, and RV in patients (1.83, 1.34,
      and 3.23 cm) were significantly lower compared with those of healthy volunteers
      (1.18, 0.62, and 2.71 cm). After fluid resuscitation, IVCe, IVCi, and RV in
      hypovolemic patients (1.75, 1.25, and 3.27 cm) significantly increased. The pre
      IVCe and the post-IVCe were closely correlated to the CVP (r = 0.585 and r =
      0.609, respectively). Similarly, the pre-RV and the post-RV were correlated to
      the CVP (r = 0.347 and r = 0.439, respectively). CONCLUSIONS: Our data
      demonstrate that the IVC and RV diameters are consistently low in patients
      undergoing gastrointestinal surgery when compared with healthy subjects.
      Ultrasonographic measurements of the IVC and RV diameters are useful supplement
      of CVP for the evaluation of preoperative patients with hypovolemia.

PMID- 24881470
TI  - Ginsenoside Rb1 improves energy metabolism in the skeletal muscle of an animal
      model of postoperative fatigue syndrome.
AB  - BACKGROUND: Postoperative fatigue syndrome (POFS) is a common clinical
      complication followed by almost every major abdominal surgery. Ginsenoside Rb1
      (GRb1), a principle ginsenoside in ginseng, could exert a potent anti-fatigue
      effect on POFS. However, the mechanism is still unknown. Previous studies
      revealed that alterations in the energy metabolism in the skeletal muscle may
      play a vital role in the development and progression of fatigue. In the present
      study, we investigate the effect of GRb1 on energy metabolism in the skeletal
      muscle of a rat model of POFS induced by major small intestinal resection.
      METHODS: GRb1 (10 mg/kg) was intraperitoneally administrated once daily for 1, 3,
      7, and 10 d from the operation day, respectively. The locomotor activity was
      recorded every day, and total food intake was calculated starting from 24 h after
      surgery. After GRb1 treatment was completed, blood and skeletal muscle were
      sampled. The level of blood glucose was determined by an automatic biochemical
      analyzer. The content of adenosine triphosphate (ATP) in skeletal muscle was
      determined by high-performance liquid chromatography. The activity of energy
      metabolic enzymes Na(+)-K(+)-ATPase, pyruvate kinase, and succinate dehydrogenase
      (SDH) was assessed by commercially available kits. RESULTS: The results revealed
      that GRb1 could increase locomotor activity of POFS rats and significantly
      increase their total food intake postoperatively (P < 0.05). Furthermore, GRb1
      also significantly increased ATP content in the skeletal muscle of POFS rats (P <
      0.05). Meanwhile, the activity of Na(+)-K(+)-ATPase and SDH in the skeletal
      muscle of POFS rats was enhanced by GRb1 (P < 0.05). However, no significant
      differences in blood glucose and pyruvate kinase were found between the POFS and
      GRb1 treatment rats (P > 0.05). CONCLUSIONS: These results suggest that GRb1 may
      improve skeletal muscle energy metabolism in POFS, and the underlying mechanism
      may be associated with an increase in the content of ATP and an enhancement in
      the activity of energy metabolic enzymes such as Na(+)-K(+)-ATPase ATPase and SDH
      in the skeletal muscle.

PMID- 24881471
TI  - Eye tracking for skills assessment and training: a systematic review.
AB  - BACKGROUND: The development of quantitative objective tools is critical to the
      assessment of surgeon skill. Eye tracking is a novel tool, which has been
      proposed may provide suitable metrics for this task. The aim of this study was to
      review current evidence for the use of eye tracking in training and assessment.
      METHODS: A systematic literature review was conducted in line with PRISMA
      guidelines. A search of EMBASE, OVID MEDLINE, Maternity and Infant Care,
      PsycINFO, and Transport databases was conducted, till March 2013. Studies
      describing the use of eye tracking in the execution, training or assessment of a
      task, or for skill acquisition were included in the review. RESULTS: Initial
      search results returned 12,051 results. Twenty-four studies were included in the
      final qualitative synthesis. Sixteen studies were based on eye tracking in
      assessment and eight studies were on eye tacking in training. These demonstrated
      feasibility and validity in the use of eye tracking metrics and gaze tracking to
      differentiate between subjects of varying skill levels. Several training methods
      using gaze training and pattern recognition were also described. CONCLUSIONS:
      Current literature demonstrates the ability of eye tracking to provide reliable
      quantitative data as an objective assessment tool, with potential applications to
      surgical training to improve performance. Eye tracking remains a promising area
      of research with the possibility of future implementation into surgical skill
      assessment.

PMID- 24881472
TI  - A nationwide analysis of clinical outcomes among newborns with esophageal atresia
      and tracheoesophageal fistulas in the United States.
AB  - BACKGROUND: The aim of this study was to examine national outcomes in newborn
      patients with esophageal atresia and tracheoesophageal fistula (EA/TEF) in the
      United Sates. METHODS: Kids' Inpatient Database (KID) is designed to identify,
      track, and analyze national outcomes for hospitalized children in the United
      States. Inpatient admissions for pediatric patients with EA/TEF for kids'
      Inpatient Database years 2000, 2003, 2006, and 2009 were analyzed. Patient
      demographics, socioeconomic measures, disposition, survival and surgical
      procedures performed were analyzed using standard statistical methods. RESULTS: A
      total of 4168 cases were identified with diagnosis of EA/TEF. The overall in
      hospital mortality was 9%. Univariate analysis revealed lower survival in
      patients with associated acute respiratory distress syndrome, ventricular septal
      defect (VSD), birth weight (BW) < 1500 g, gestational age (GA), time of operation
      within 24 h of admission, coexisting renal anomaly, imperforate anus, African
      American race, and lowest economic status. Multivariate logistic regression
      identified BW < 1500 g (odds ratio [OR] = 4.5, P < 0.001), operation within 24 h
      (OR = 6.9, P < 0.001), GA <28 wk (OR = 2.2, P < 0.030), and presence of VSD (OR =
      3.8, P < 0.001) as independent predictors of in-hospital mortality. Children's
      general hospital and children's unit in a general hospital were found to have a
      lower mortality rate compared with not identified as a children's hospital after
      excluding immediate transfers (P = 0.008). CONCLUSIONS: BW < 1500 g, operation
      within 24 h, GA < 28 wk, and presence of VSD are the factors that predict higher
      mortality in EA/TEF population. Despite dealing with more complicated cases,
      children's general hospital and children's unit in a general hospital were able
      to achieve a lower mortality rate than not identified as a children's hospital.

PMID- 24881473
TI  - Photodynamic therapy for psoriasis.
AB  - INTRODUCTION: Photodynamic therapy for psoriasis showed promise in the early
      1990s with reports of plaque clearance following topical aminolevulinic acid -
      photodynamic therapy (ALA-PDT). METHODS: In December 2013, we conducted a
      systematic search of the PubMed Medline database using the keywords "psoriasis"
      and "photodynamic therapy". RESULTS: Numerous clinical studies have failed to
      demonstrate a consistent, efficacious response to topical ALA-PDT. Furthermore,
      severe pain and burning sensations were repeatedly reported, many cases being
      intolerable for patients. DISCUSSION: The variability in clinical response and
      the painful side effects have made topical ALA-PDT an unsuitable treatment option
      for chronic plaque psoriasis. Nonetheless, early clinical studies of other
      modalities such as topical hypericin and methylene blue, as well as systemic ALA
      and verteporfin, have shown that these photosensitizers are efficacious and much
      better tolerated than topical ALA. CONCLUSION: With the current landscape of
      phototherapy dominated by psoralen combined with ultraviolet A (PUVA) and narrow
      band ultraviolet B (NB-UVB), an alternative light therapy utilizing the visible
      spectrum is certainly promising and a worthwhile endeavor to pursue.

PMID- 24881474
TI  - [Surgical rectocele repair - many techniques, few unambiguous conclusions].
AB  - INTRODUCTION: Surgical treatment of rectocele represents a controversial issue on
      the boundary between medical specialisations with many different corrective
      surgical techniques. Is it possible, based on the available knowledge, to
      determine an optimal operative technique for rectocele repair? METHODS: Complex
      literature search focusing on the identification of rectocele surgical repair
      studies in the MEDLINE, PubMed and Google Scholar databases. The aim of this
      paper is to offer a comprehensive review of the contemporary situation as regards
      rectocele surgical repair. RESULTS: There are four main possible approaches for
      rectocele repair - transvaginal, transanal, transperineal and transabdominal.
      Posterior colporrhaphy with levatoroplasty is the traditional transvaginal
      technique, performed at most gynaecological departments in various modifications.
      Defect-specific rectocele repair and mesh repair represent newer transvaginal
      techniques which offer better postoperative functional results, although with the
      risk of possible serious complications. Traditional transanal rectocele repair
      (vertical and horizontal plication of the rectovaginal septum) is currently
      performed only rarely due to its worse results in comparison with the
      transvaginal approach. Rectal resection using endostaplers (STARR and TRANSTAR
      techniques) is a modern transanal technique. Stapled rectocele repair leads to
      the correction of anorectal anatomical conditions and to the improvement of
      obstructive defecation symptoms with acceptable morbidity. Transperineal approach
      is usually used in patients with rectocele and anal incontinence due to a proven
      sphincter defect. Transabdominal laparoscopic approach is based on
      vaginorectopexy by means of mesh implantation, and it is indicated especially in
      patients with rectocele and enterocele. CONCLUSION: Based on the results of
      published studies, it is not possible to determine clear guidelines for rectocele
      surgical repair. Posterior colporrhaphy and stapled transanal repair are the most
      common techniques in practice. Prospective randomized studies focusing on the
      comparison between transvaginal and stapled transanal approach for rectocele
      repair are needed.

PMID- 24881475
TI  - [Pulmonary metastases - 12-year experience with surgical therapy].
AB  - INTRODUCTION: Nowadays, radical surgical therapy of selected secondary pulmonary
      tumours is a generally accepted therapeutic procedure that has been proven to
      extend long-term survival of the patients with acceptable perioperative morbidity
      and mortality. The authors present a retrospective analysis of a set of patients
      who underwent surgery for pulmonary metastases of various tumours in a 12-year
      period. MATERIAL AND METHODS: In 2001-2012, 159 patients with secondary pulmonary
      tumours were operated on at the authors department, of whom 80 were men; the
      median age was 65 years. Solitary metastases were present in 112 patients
      (70.4%); the other patients had multiple metastases; 24 patients (15.1 %)
      suffered from bilateral involvement, and 6 patients (3.8%) suffered from relapsed
      metastatic disease after previous radical surgery. Colorectal carcinoma
      metastases were diagnosed in most cases (75 people - 47.2%). The median disease
      free period from the surgery of the primary tumour was 27 months in the patient
      set. RESULTS: In total, 166 unilateral (87.4%) and 24 bilateral surgeries were
      performed using one- or two-stage procedure (12.6%). Precise laser excisions
      represented the most common type of surgery (59 procedures - 31.1%). In total,
      296 metastases were radically resected, and 13 were treated using radiofrequency
      ablation. Perioperative morbidity was 13.2% with a zero lethality rate. 90
      operated patients (56.6%) still survive after the metastasectomy, with median
      survival of 44 months. The overall 3-year survival in the set was 59%, and 5-year
      survival was 39%. The number of metastases is a statistically significant factor
      affecting survival in the patient cohort with colorectal carcinoma metastases,
      the risk of death being 2.7 times higher in patients with 2 and more colorectal
      carcinoma metastases. 68 patients (42.8%) live without progression of the disease
      after the metastasectomy, with the median disease-free interval of 29 months. In
      total, 43% of the patients were free of any signs of relapse or disease
      progression for 3 years, and 27% for 5 years. The risk of disease progression is
      2.1 times higher in patients with 2 and more metastases of any tumour, and for
      colorectal carcinoma this risk is 2.3 times higher. CONCLUSION: The achieved
      results confirm the positive role of pulmonary metastasectomy in disseminated
      tumour therapy. The number of metastases is the decisive prognostic factor
      affecting both long-term survival of operated patients and their DFI.

PMID- 24881476
TI  - [A pilot study: correction of the levator hiatus using an anal sling as a
      surgical treatment of faecal incontinence].
AB  - INTRODUCTION: Faecal incontinence is a significantly depressing and mentally
      devastating disability. Surgical treatment, as a first choice method, is
      indicated for incontinence originating as a result of traumatic or iatrogenic
      infliction of the sphincter apparatus, particularly of the external sphincter. In
      case of idiopathic (neurogenic) incontinence, it is indicated very exceptionally,
      if ever. The authors present a pilot study to verify the possibility of surgical
      treatment of anal incontinence with the support of a puborectal muscle loop by
      means of the absorbable STRATASIS(r) TF mesh. MATERIAL AND METHODS: In the years
      2010-2012, eight experimental surgical procedures were performed. Female patients
      with a history of faecal incontinence of the third stage longer than one year and
      with EMG-verified neurological lesion were recruited. The evaluating criteria
      were the Wexner score and changes in the levator and anorectal angle acquired
      from a MR defecographic examination performed before and six months after the
      operation. RESULTS: The complaints improved distinctly in six patients; in the
      two remaining cases, the method failed completely. The failures were associated
      with an inflammatory complication in both cases. In one patient, the authors do
      not rule out an incorrect indication, too. The Wexner score decreased from 18 to
      10 in improved patients. Changes in the levator and anorectal angle were not
      significant. CONCLUSION: The results confirm the possibility of successful
      surgical influence on incontinence of the third stage by correcting the levator
      hiatus with biodegradable mesh. Continence improvement persists even after the
      mesh transforms into scar tissue.

PMID- 24881477
TI  - [Long-term follow-up results after open small umbilical hernia repairs].
AB  - INTRODUCTION: Adult umbilical hernia is a common surgical condition in the fifth
      and sixth decade of life. Despite the high frequency of umbilical hernia repairs,
      disappointingly high recurrence rates after simple suture repairs are reported,
      amounting to 54%. In addition, it is reported that with the rising frequency of
      recurrences, the size of the hernial sac and gate gradually increases. Therefore
      we decided to find out the incidence of recurrences after operative repair of an
      umbilical hernia at our department. MATERIAL AND METHODS: Patient data for this
      retrospective study focusing on the period between 2006 and 2010 were obtained
      from the electronic hospital database. Patients with umbilical hernia and the
      abdominal wall defect up to 3 cm who underwent primary elective procedure were
      included in the study. Patients with incisional hernias were excluded. All
      patients were contacted at least 3 years after operation to confirm the accuracy
      of data. RESULTS: A total of 127 patients were included in this study. In the
      abovementioned period, no mesh was used during primary surgery in any of the
      patients. Recurrence occurred in a total of 13.4% of patients. Approximately 40%
      of patients with the first recurrence were re-operated at our department, 30% of
      patients were re-operated in other hospitals and the rest have not sought medical
      attention in respect of the recurrence. Patients with recurrence did not differ
      from the others as regards age, body mass index or surgical site infection
      development. CONCLUSION: Due to the high recurrence rates after operative sutures
      of the umbilical hernias there is a need to thoroughly consider the potential
      risk factors such as the body mass index and the abdominal wall defect size.
      Therefore, it is recommended to use the mesh more widely during primary surgery,
      especially in obese patients with BMI over 30 and the wall defect size exceeding
      3 cm. The question remains whether to use the mesh in all overweight patients and
      with wall defect smaller than 3 cm.

PMID- 24881478
TI  - [Intestinal endometriosis - a case report].
AB  - Endometriosis is defined as the presence of functional endometrial tissue outside
      the uterine cavity. The most common clinical symptoms of endometriosis are
      infertility and chronic pelvic pain. Endometriosis affects 8-10% of women of
      reproductive age and the condition is highly associated with infertility. Ectopic
      endometrial tissue is usually found in the small pelvis and the peritoneum, but
      endometrial tissue deposits have also been reported in other anatomical locations
      in the human body. We describe the case of a young patient with persistent
      abdominal pain and bleeding via the rectum during menstrual periods, hospitalised
      at the Second Department of Surgery, Pavol Jozef Safarik University, Faculty of
      Medicine and Louis Pasteur University Hospital Kosice.

PMID- 24881479
TI  - [Severe acute pancreatitis - managing complications using a combination of
      minimally invasive approaches].
AB  - In this case report, we describe the case of a 30-year-old obese patient with
      severe acute pancreatitis complicated during hospitalization by the development
      of infected necrosis, a pseudocyst and an abscess. We demonstrate a possible
      solution to these complications using a combination of minimally invasive
      approaches. The contribution of this case report resides in that it presents a
      combination of the percutaneous approach and the endosonographic approach in the
      treatment of pancreatic necrosis. We believe that in such an extensive necrosis
      of the pancreas as is described in our case, this combined approach is optimal.
      The condition for implementing such a procedure is a well-staffed and technically
      equipped workplace.

PMID- 24881480
TI  - [Complications of hemorrhoids].
AB  - The most common and serious complications of haemorrhoids include perianal
      thrombosis and incarcerated prolapsed internal haemorrhoids with subsequent
      thrombosis. They are characterised by severe pain in the perianal region possibly
      with bleeding. In a short history of the perianal thrombosis, acute surgical
      incision or excision is indicated, which can result in rapid relief of the
      painful symptoms. In incarcerated prolapsed internal haemorrhoids, emergency
      haemorrhoidectomy may also be indicated. Segmental haemorrhoidectomy in the most
      affected quadrants followed by further elective surgery for haemorrhoids in the
      next stage is preferred.

PMID- 24881481
TI  - [Acute periproctal abscesses].
AB  - Periproctal inflammations related to the anus are characterized by the rapid
      spread of the infection to the surrounding tissue, which is determined by the
      anatomical characteristics and infectious agents. Inflammation, which starts as a
      phlegmon, quickly forms boundaries and an abscess develops in most cases. Up to
      80-90% of anorectal abscesses develop according to the crypto-glandular theory on
      the basis of infection of the anal glands, spilling into the Morgagni crypts in
      the anal canal. Up to two-thirds of such abscesses are associated with the
      emergence of anorectal fistulas. Anorectal abscesses can be divided into marginal
      and subcutaneous perianal abscesses, submucosal, intersphincteric, ischiorectal
      and supralevator abscesses. Their diagnosis is based on thorough physical
      examination, sometimes also with the help of imaging methods such as computed
      tomography, magnetic resonance imaging and endoanal ultrasound. What is decisive
      for the successful treatment of anorectal abscessess is their early and adequate
      surgical drainage. Adjuvant antibiotic therapy is necessary only when the overall
      signs of sepsis are present and for patients with a comorbidity such as diabetes,
      valvular heart disease, or immunodeficiency.

PMID- 24881482
TI  - [Anorectal injury].
AB  - Anal and rectal traumas are relatively rare (with the exception of iatrogenic
      damage) due to the anatomical position of the anorectum. The anal canal is
      injured more frequently due to its relatively superficial position, but injuries
      involving the extraperitoneal rectum, although more rare, tend to be much more
      severe and may affect the surrounding organs. Intraperitoneal rectal injury is
      associated with bleeding or perforation and may lead to peritonitis and diffuse
      contamination of the abdominal cavity. The decisive factor is the early detection
      of the injury and early initiation of treatment. The first step in surgical
      treatment of severe anorectal injury is the control of massive bleeding and
      volume resuscitation. The aim of the surgery is to preserve life, control
      infections and to preserve the patients anal continence and evacuation function.
      Key words: anorectal trauma - aetiology - surgical treatment. 

PMID- 24881483
TI  - Exploring cattle movements in Belgium.
AB  - Movement of animals from one farm to another is a potential risk and can lead to
      the spreading of livestock diseases. Therefore, in order to implement effective
      control measures, it is important to understand the movement network in a given
      area. Using the SANITEL data from 2005 to 2009, around 2 million cattle movements
      in Belgium were traced. Exploratory analysis revealed different spatial
      structures for the movement of different cattle types: fattening calves are
      mostly moved to the Antwerp region, adult cattle are moved to different parts in
      Belgium. Based on these differences, movement of cattle would more likely cause a
      spread of disease to a larger number of areas in Belgium as compared to the
      fattening calves. A closer inspection of the spatial and temporal patterns of
      cattle movement using a weighted negative binomial model, revealed a significant
      short-distance movement of bovine which could be an important factor contributing
      to the local spreading of a disease. The model however revealed hot spot areas of
      movement in Belgium; four areas in the Walloon region (Luxembourg, Hainaut, Namur
      and Liege) were found as hot spot areas while East and West Flanders are
      important "receivers" of movement. This implies that an introduction of a disease
      to these Walloon regions could result in a spread toward the East and West
      Flanders regions, as what happened in the case of Bluetongue BTV-8 outbreak in
      2006. The temporal component in the model also revealed a linear trend and short-
      and long-term seasonality in the cattle movement with a peak around spring and
      autumn. The result of this explorative analysis enabled the identification of
      "hot spots" in time and space which is important in enhancing any existing
      monitoring and surveillance system. 

PMID- 24881485
TI  - Concerted ligand exchange and the roles of counter anions in the reversible
      structural switching of crystalline peptide metallo-macrocycles.
AB  - To understand reversible structural switching in crystalline materials, we
      studied the mechanism of reversible crystal-to-crystal transformation of a
      tetranuclear Ni(II) macrocycle consisting of artificial beta-dipeptides. On the
      basis of detailed structural analyses and thermodynamic measurements made in a
      comparison of pseudo-isostructural crystals (NO3 and BF4 salts), we herein
      discuss how ligand-exchange reactions take place in the crystal due to changes in
      water content and temperature. Observations of the structural transformation of
      NO3 salt indicated that a pseudo crystalline phase transformation takes place
      through concerted ligand-exchange reactions at the four Ni(II) centers of the
      macrocycle with hydrogen bond switching. A mechanism for this ligand exchange was
      supported by IR spectroscopy. Thermodynamic measurements suggested that the
      favorable compensation relationship of the enthalpy changes due to water uptake
      and structural changes are keys to the reversible structural transformation. On
      the basis of a comparison with the pseudo-isostructural crystals, it is apparent
      that the crystal packing structure and the types of counter anions are important
      factors for facilitating reversible ligand exchange with single crystallinity. 

PMID- 24881484
TI  - Life events are positively associated with luteinizing hormone in middle age
      adult men: role of cortisol as a third variable.
AB  - Previous studies have tested the relationship between chronic stress and sex
      hormones, but inconsistent results have been found. One possibility is that this
      association may depend on other biological factors. This study examined the
      relationship between stressful life events (LE) and sex hormones in men, and
      whether cortisol is involved in this relationship. From a total number of 2906
      men who completed a screening for the early detection of prostate cancer, 139
      healthy men (mean +/- SD age, 57.8 +/- 5.7 years) were included in this study.
      Participants were assessed with the Holmes and Rahe questionnaire in relation to
      their experience of LE during the previous 1-5 years. Salivary and serum cortisol
      was measured at 08:00-09:00 h, as well as luteinizing hormone (LH), total
      testosterone, epinephrine (E) and norepinephrine (NE). LE weight sum and LE
      number positively correlated with LH (r = 0.293, p = 0.004; r = 0.220, p = 0.031,
      respectively). In a multiple regression analysis, LE-sum explained an additional
      and significant 10.4% of the variance in LH levels, after statistically
      controlling for the effects of age, waist circumference (WC) and BMI (F(1,90) =
      6.61, p < 0.05). Importantly, cortisol interacted with LE in relation to total
      testosterone. In men with high cortisol values (>=15.4 ug/dl), there was a
      statistically significant positive relationship between LE number and total
      testosterone levels (p = 0.05), while LE were unrelated to total testosterone in
      men with low cortisol. LE correlated with sex hormones, predicting LH values, and
      in men with high cortisol levels shows a possible moderator effect of cortisol on
      the relationship between LE and total testosterone.

PMID- 24881486
TI  - Photochemical reactivity of the iron(III) complex of a mixed-donor, alpha-hydroxy
      acid-containing chelate and its biological relevance to photoactive marine
      siderophores.
AB  - The trimeric clusters [Fe(III)3(X-Sal-AHA)3(MU3-OCH3)](-), where X-Sal-AHA is a
      tetradentate chelate incorporating an alpha-hydroxy acid moiety (AHA) and a
      salicylidene moiety (X-Sal with X being 5-NO2, 3,5-diCl, all-H, 3-OCH3, or 3,5-di
      t-Bu substituents on the phenolate ring), undergo a photochemical reaction
      resulting in reduction of two Fe(III) to Fe(II) for each AHA group that is
      oxidatively cleaved. However, photolysis of structurally analogous mixed Fe/Ga
      clusters demonstrate that a similar photolysis reaction will occur with only a
      single Fe(III) in the cluster. Quantum yields of iron reduction for the series of
      [Fe(III)3(X-Sal-AHA)3(MU3-OCH3)](-) complexes measured by monitoring Fe(II)
      production are twice those for ligand oxidation, measured by loss of the CD
      signal for the complex due to cleavage of the chiral AHA group.The quantum
      yields, 2-13% in the UVA and UVB ranges, are higher for complexes with electron
      withdrawing X groups than for those with electron-donating X groups [corrected].
      The observed final photolysis product of the chelate is different if irradiation
      is done in the air than if it is done under Ar. The first observed photochemical
      product is the aldehyde resulting from decarboxylation of the AHA. This is the
      final product under anaerobic conditions. In air, this is followed by an Fe- and
      O2-dependent reaction oxidizing the aldehyde to the corresponding carboxylate,
      then a second Fe- and light-dependent decarboxylation reaction giving a product
      that is two carbons smaller than the initial ligand. These reactivity studies
      have important biological implications for the photoactive marine siderophores.
      They suggest that different types of photochemical products for different
      siderophore structure types do not result from different initial photochemical
      steps, but rather from different susceptibility of the initial photochemical
      product to air oxidation.

PMID- 24881487
TI  - Fe(III) bipyrrolidine phenoxide complexes and their oxidized analogues.
AB  - Fe(III) complexes of the symmetric (2S,2'S)-[N,N'-bis(1-(2-hydroxy-3,5-di-tert
      butylphenylmethyl))]-2,2'-bipyrrolidine (H2L(1)) and dissymmetric (2S,2'S)-[N,N'
      (1-(2-hydroxy-3,5-di-tert-butylphenylmethyl))-2-(pyridylmethyl)]-2,2'
      bipyrrolidine (HL(2)) ligands incorporating the bipyrrolidine backbone were
      prepared, and the electronic structure of the neutral and one-electron oxidized
      species was investigated. Cyclic voltammograms (CV) of FeL(1)Cl and FeL(2)Cl2
      showed expected redox waves corresponding to the oxidation of phenoxide moieties
      to phenoxyl radicals, which was achieved by treating the complexes with 1 equiv
      of a suitable chemical oxidant. The clean conversion of the neutral complexes to
      their oxidized forms was monitored by UV-vis-NIR spectroscopy, where an intense
      pi-pi* transition characteristic of a phenoxyl radical emerged ([FeL(1)Cl](+*):
      25,500 cm(-1) (9000 M(-1) cm(-1)); [FeL(2)Cl2](+*): 24,100 cm(-1) (8300 M(-1) cm(
      1)). The resonance Raman (rR) spectra of [FeL(1)Cl](+*) and [FeL(2)Cl2](+*)
      displayed the characteristic phenoxyl radical nu7a band at 1501 and 1504 cm(-1),
      respectively, confirming ligand-based oxidation. Electron paramagnetic resonance
      (EPR) spectroscopy exhibited a typical high spin Fe(III) (S = 5/2) signal for the
      neutral complexes in perpendicular mode. Upon oxidation, a signal at g ~ 9 was
      observed in parallel mode, suggesting the formation of a spin integer system
      arising from magnetic interactions between the high spin Fe(III) center and the
      phenoxyl radical. Density functional theory (DFT) calculations further supports
      this formulation, where weak antiferromagnetic coupling was predicted for both
      [FeL(1)Cl](+*) and [FeL(2)Cl2](+*).

PMID- 24881488
TI  - Evaluation of acotiamide for the treatment of functional dyspepsia.
AB  - INTRODUCTION: The treatment for functional dyspepsia (FD) (indigestion) remains
      unsatisfactory. Acotiamide is a new prokinetic that has been recently approved
      and used in Japan for the treatment of FD. AREAS COVERED: This review introduces
      the pharmacodynamics, pharmacokinetics and efficacy data from current clinical
      trials from literature sourced using the PubMed search tools. Future principles
      for developing drugs and designing clinical trials to test them for treating FD
      are also discussed. EXPERT OPINION: Acotiamide can contribute to the treatment of
      the specific subset of symptoms defined as postprandial FD by reducing the
      impaired fundic relaxation and accommodation after eating. The agent has the
      added benefit of a very good safety profile.

PMID- 24881489
TI  - Evaluation of clinical performance of a novel urine-based HPV detection assay
      among women attending a colposcopy clinic.
AB  - BACKGROUND: Human papillomavirus (HPV) testing in urine offers a convenient
      approach for cervical cancer screening but has previously suffered from limited
      clinical sensitivity. OBJECTIVES: We evaluated clinical performance of the
      prototype Trovagene HPV test, a novel polymerase chain reaction assay that
      targets the E1 region of the HPV genome and detects and amplifies short fragments
      of cell-free HPV DNA in urine. STUDY DESIGN: We conducted a pilot study among 72
      women referred to colposcopy following abnormal screening. Participants provided
      a urine sample prior to clinician-collected cervical sampling and colposcopically
      directed punch biopsy. Trovagene HPV test results on urine samples were compared
      with cervical and urine testing by Linear Array HPV Genotyping Test (LA-HPV) for
      detection of histologically-confirmed cervical precancerous lesions. RESULTS:
      There was high concordance between urine samples tested by the Trovagene HPV test
      and corresponding cervical (87.5%) and urine (81.9%) samples tested by LA-HPV.
      The Trovagene HPV test had high sensitivity (92.3% for detecting CIN2/3, and 100%
      for CIN3), comparable to LA-HPV testing on cervical samples (96.0% and 100%,
      respectively), and higher than LA-HPV testing on urine samples (80.8% and 90.0%,
      respectively). In this referral population, the specificity of the Trovagene
      urine HPV test was non-significantly lower (29% for CIN2/3 and 25% for CIN3) than
      corresponding estimates of LA-HPV testing on cervical (36% and 28%, respectively)
      and urine (42% and 38%, respectively) samples. CONCLUSIONS: This pilot study
      suggests that the Trovagene HPV test has high sensitivity for urine-based
      detection of cervical precancer and merits evaluation in larger studies.

PMID- 24881490
TI  - Universal neonatal cytomegalovirus screening using saliva - report of clinical
      experience.
AB  - OBJECTIVES: To analyze the results of a neonatal universal screen for congenital
      cytomegalovirus (CMV) using saliva real-time polymerase chain reaction (rt-PCR).
      STUDY DESIGN: During one year (15/5/2011-15/5/2012), saliva was collected from
      9845 infants (97% of 10,137 newborns). Viral DNA was extracted by Magna-Pure LC
      (Roche) and was tested for the presence of CMV IE and gB genes. Urine culture was
      collected from positive infants for confirmation. For all infants with congenital
      CMV maternal data were collected and head ultrasound, blood count, liver enzymes,
      retinal examination and auditory brainstem response testing were performed.
      Parents were notified in advance and had the option to avoid screening. The
      ethical committee approved retrospective analysis of the data. RESULTS: Fifty six
      infants (0.57%) had a positive saliva assay. Of these, 47 were confirmed by urine
      rt-PCR and culture, in another one maternal sero-conversion was documented during
      pregnancy (48 infants). Twenty-eight mothers (28/47, 60%) had primary infection
      during pregnancy, 14 (30%) had non-primary infection, and no serological data
      were obtained from five (10%). Four infants (8.5%), two with prenatal diagnosis
      of CMV and normal fetal brain imaging and two born to mothers sero-positive
      before pregnancy, exhibited symptoms related to CMV and were offered antivirals.
      Hearing impairment was diagnosed in two infants (late onset HI in one case).
      CONCLUSIONS: Saliva rt-PCR assay is a feasible and effective means of universal
      neonatal CMV screening that can detect affected infants who might benefit from
      treatment and follow-up. The long-term clinical significance of screening and its
      cost effectiveness are yet to be determined.

PMID- 24881492
TI  - Primary systemic therapy and whole breast irradiation for locally advanced breast
      cancer: a systematic review.
AB  - The current management of locally advanced breast cancer (LABC) is based on tri
      modality treatment including chemotherapy, radiotherapy and surgery. The concept
      of preoperative concurrent or sequential chemoradiation for LABC was initially
      reported more than a decade ago; however this concept did not gain popularity
      because of the low benefit/risk ratio and the lack of strong data supporting the
      concept. The purpose of the current systematic review was to explore the
      published data about preoperative chemoradiation (sequential and/or concurrent)
      using whole breast irradiation in terms of toxicity and outcome. 

PMID- 24881491
TI  - Virological characteristics of occult hepatitis B virus in a North American
      cohort of human immunodeficiency virus type 1-positive patients on dual active
      anti-HBV/HIV therapy.
AB  - BACKGROUND: Occult hepatitis B virus infection (OBI) is defined as low-level HBV
      DNA presence in serum, liver and/or peripheral blood mononuclear cells (PBMC) in
      individuals that lack serum hepatitis B virus surface antigen (HBsAg). HIV+
      patients with OBI may be at risk for HBV reactivation, and often receive dual
      active anti-HBV/HIV therapy, such as lamivudine (LMV). OBJECTIVES: To determine
      the presence of OBI in a North American cohort of HIV-1-positive patients. STUDY
      DESIGN/METHODS: 45 HIV-1-positive, serum HBsAg-negative patients, reactive for
      antibodies to HBV core antigen (anti-HBc), were tested for HBV DNA in plasma and
      for HBV DNA and covalently closed circular DNA (cccDNA) in PBMC. Ten patients
      were re-tested after ~5-10 years, including genotyping and clonal sequence
      analysis of the HBV polymerase (P) gene and overlapping HBV surface (S) gene from
      8 PBMC samples. RESULTS: Overall, 42% (19/45) tested HBV DNA positive, especially
      in PBMC (18/45), including 3/18 that were reactive for HBV cccDNA, compared to
      17% (8/45) that were HBV DNA reactive in plasma. In 8 patients on LMV, sequence
      analysis in PBMC showed that all were HBV genotype C or D. Several carried HBV P
      region variants at residues associated with anti-HBV drug resistance and
      overlapping S gene region within the major HBsAg "a determinant". CONCLUSION: OBI
      is common in HIV-positive, anti-HBc reactive patients on anti-HBV/HIV therapy,
      particularly in PBMC. HBV sequence analysis revealed that all had HBV genotype C
      or D and often had P/overlapping S gene variants possibly associated with dual
      active anti-HIV/HBV therapy.

PMID- 24881493
TI  - Getting Wrinkly Spreaders to demonstrate evolution in schools.
AB  - Understanding evolution is crucial to modern biology, but most teachers would
      assume that practical demonstrations of evolution in school laboratories are
      unfeasible. However, perhaps they have not heard of 'evolution in a test tube'
      and how Wrinkly Spreaders can form the basis for both practical demonstrations of
      bacterial evolution and further work. 

PMID- 24881463
TI  - Adjuvant exemestane with ovarian suppression in premenopausal breast cancer.
AB  - BACKGROUND: Adjuvant therapy with an aromatase inhibitor improves outcomes, as
      compared with tamoxifen, in postmenopausal women with hormone-receptor-positive
      breast cancer. METHODS: In two phase 3 trials, we randomly assigned premenopausal
      women with hormone-receptor-positive early breast cancer to the aromatase
      inhibitor exemestane plus ovarian suppression or tamoxifen plus ovarian
      suppression for a period of 5 years. Suppression of ovarian estrogen production
      was achieved with the use of the gonadotropin-releasing-hormone agonist
      triptorelin, oophorectomy, or ovarian irradiation. The primary analysis combined
      data from 4690 patients in the two trials. RESULTS: After a median follow-up of
      68 months, disease-free survival at 5 years was 91.1% in the exemestane-ovarian
      suppression group and 87.3% in the tamoxifen-ovarian suppression group (hazard
      ratio for disease recurrence, second invasive cancer, or death, 0.72; 95%
      confidence interval [CI], 0.60 to 0.85; P<0.001). The rate of freedom from breast
      cancer at 5 years was 92.8% in the exemestane-ovarian suppression group, as
      compared with 88.8% in the tamoxifen-ovarian suppression group (hazard ratio for
      recurrence, 0.66; 95% CI, 0.55 to 0.80; P<0.001). With 194 deaths (4.1% of the
      patients), overall survival did not differ significantly between the two groups
      (hazard ratio for death in the exemestane-ovarian suppression group, 1.14; 95%
      CI, 0.86 to 1.51; P=0.37). Selected adverse events of grade 3 or 4 were reported
      for 30.6% of the patients in the exemestane-ovarian suppression group and 29.4%
      of those in the tamoxifen-ovarian suppression group, with profiles similar to
      those for postmenopausal women. CONCLUSIONS: In premenopausal women with hormone
      receptor-positive early breast cancer, adjuvant treatment with exemestane plus
      ovarian suppression, as compared with tamoxifen plus ovarian suppression,
      significantly reduced recurrence. (Funded by Pfizer and others; TEXT and SOFT
      ClinicalTrials.gov numbers, NCT00066703 and NCT00066690, respectively.).

PMID- 24881495
TI  - Enhanced performance of a three-zone simulated moving bed chromatography for
      separation of succinic acid and lactic acid by simultaneous use of port-location
      rearrangement and partial-feeding.
AB  - The performance of a three-zone simulated moving bed (SMB) chromatographic
      process for separation of succinic acid and lactic acid has been improved to a
      certain extent in previous researches by applying either a partial-feeding (PF)
      or a port-location rearrangement (PR) to its operation. To make a further
      improvement, the strategy of applying both PF and PR simultaneously to the three
      zone SMB operation was proposed in this study. The results from both equilibrium
      theory analysis and detailed simulation proved that the proposed strategy, which
      was called PF-PR in this article, had the benefit of a synergy between the
      individual merits of PF and PR in the three-zone SMB performance. As a
      consequence, the PF-PR mode could surpass the PF and the PR modes by a wide
      margin and the classical mode by a dramatic margin in the aspects of separation
      performance and throughput. 

PMID- 24881494
TI  - Three families with Perry syndrome from distinct parts of the world.
AB  - OBJECTIVES: Perry syndrome consists of autosomal dominant Parkinsonism,
      depression, weight loss, and central hypoventilation. Eight mutations in 16
      families have been reported: p.F52L, p.G67D, p.G71R, p.G71E, p.G71A, p.T72P,
      p.Q74P, and p.Y78C located in exon 2 of the dynactin 1 (DCTN1) gene on chromosome
      2p13.1. METHODS: Genealogical, clinical, genetic, and functional studies were
      performed in three kindreds from New Zealand, the United States, and Colombia. A
      diaphragmatic pacemaker was implanted in the proband from the Colombian family to
      treat her respiratory insufficiency. Dopaminergic therapy was initiated in
      probands from two families. RESULTS: Besides the probands, 17 symptomatic
      relatives from all families were identified. The cardinal signs of Perry syndrome
      were present in all three probands with symptomatic disease onset in their fifth
      or sixth decade of life. Parkinsonism was moderate with a partial response to
      dopaminergic treatment. All affected persons but two died of respiratory
      insufficiency. The proband from the Colombian family is alive most likely due to
      early diagnosis and implantation of a diaphragmatic pacemaker. Two-and-a-half
      year follow-up examination has revealed that the diaphragmatic pacemaker is
      optimally functioning without any major complications. In the Colombian and US
      families, the DCTN1 p.G71R and in the New Zealand family the DCTN1 p.Y78C
      mutations were identified. In functional assays, both mutations altered
      microtubule binding consistent with a pathogenic role. CONCLUSIONS: Perry
      syndrome is a rare condition, but new cases are expected to be diagnosed
      worldwide. Early diagnosis prevents life-threatening acute respiratory failure.
      Diaphragmatic pacemakers should be considered as an effective symptomatic
      treatment option.

PMID- 24881496
TI  - Direct determination of flavor relevant and further branched-chain fatty acids
      from sheep subcutaneous adipose tissue by gas chromatography with mass
      spectrometry.
AB  - 4-Methyloctanoic acid, 4-ethyloctanoic acid and 4-methylnonanoic acid are key
      flavor compounds of sheep and goat. Yet, the low amounts of these volatile
      branched-chain fatty acids (vBCFAs) in the fat of the ruminants hampered their
      determination on a routine basis. In this work we developed a gas
      chromatography/mass spectrometry selected ion monitoring (GC/MS-SIM) method for
      the direct determination of the vBCFAs as methyl esters, which were obtained
      after transesterification of subcutaneous adipose tissue of sheep. The excellent
      sensitivity of the GC/MS-SIM method (limit of quantification, LOQ, 3.6-4.8MUg/g;
      limit of detection, LOD, 1.1-1.4MUg/g for 4-Me-8:0, 4-Et-8:0 and 4-Me-9:0)
      enabled us to determine the three vBCFAs without an enrichment step. Subcutaneous
      adipose sheep tissue of three different breeds contained 23-88MUg/g 4
      methyloctanoic acid, 13-26MUg/g 4-ethyloctanoic acid and ~2.9-18MUg/g 4
      methylnonanoic acid. Since all fatty acids were present in the FAME fraction, the
      samples could be screened for further branched-chain FAMEs. After elimination of
      unsaturated fatty acids by hydrogenation (the presence of some unsaturated fatty
      acids could be verified by this measure), additional measurements in SIM and full
      scan modes of methyl esters and picolinyl esters enabled the determination of
      further 97 saturated fatty acids in the samples with eight to 20 carbons. The
      method is suited for routine analysis and may be useful to investigate the
      reasons for the abundance/absence of 4-methyloctanoic acid, 4-ethyloctanoic acid
      and 4-methylnonanoic acid and further branched-chain fatty acids in sheep and
      goat. 

PMID- 24881497
TI  - Reduction of nasal Staphylococcus aureus carriage in health care professionals by
      treatment with a nonantibiotic, alcohol-based nasal antiseptic.
AB  - BACKGROUND: Antibiotics used to reduce nasal colonization by Staphylococcus
      aureus in patients before admission are inappropriate for carriage reduction on a
      regular basis within a hospital community. Effective nonantibiotic alternatives
      for daily use in the nares will allow reduction of this bacterial source to be
      addressed. METHODS: Our study tested the effectiveness of a nonantibiotic,
      alcohol-based antiseptic in reducing nasal bacterial carriage in health care
      professionals (HCPs) at an urban hospital center. HCPs testing positive for
      vestibular S aureus colonization were treated 3 times during the day with topical
      antiseptic or control preparations. Nasal S aureus and total bacterial
      colonization levels were determined before and at the end of a 10-hour workday.
      RESULTS: Seventy-eight of 387 HCPs screened (20.2%) tested positive for S aureus
      infection. Of 39 subjects who tested positive for S aureus infection who
      completed the study, 20 received antiseptic and 19 received placebo treatment.
      Antiseptic treatment reduced S aureus colony forming units from baseline by 99%
      (median) and 82% (mean) (P < .001). Total bacterial colony forming units were
      reduced by 91% (median) and 71% (mean) (P < .001). CONCLUSIONS: Nasal application
      of a nonantibiotic, alcohol-based antiseptic was effective in reducing S aureus
      and total bacterial carriage, suggesting the usefulness of this approach as a
      safe, effective, and convenient alternative to antibiotic treatment.

PMID- 24881498
TI  - Statistical image reconstruction for low-dose CT using nonlocal means-based
      regularization.
AB  - Low-dose computed tomography (CT) imaging without sacrifice of clinical tasks is
      desirable due to the growing concerns about excessive radiation exposure to the
      patients. One common strategy to achieve low-dose CT imaging is to lower the
      milliampere-second (mAs) setting in data scanning protocol. However, the
      reconstructed CT images by the conventional filtered back-projection (FBP) method
      from the low-mAs acquisitions may be severely degraded due to the excessive
      noise. Statistical image reconstruction (SIR) methods have shown potentials to
      significantly improve the reconstructed image quality from the low-mAs
      acquisitions, wherein the regularization plays a critical role and an established
      family of regularizations is based on the Markov random field (MRF) model.
      Inspired by the success of nonlocal means (NLM) in image processing applications,
      in this work, we propose to explore the NLM-based regularization for SIR to
      reconstruct low-dose CT images from low-mAs acquisitions. Experimental results
      with both digital and physical phantoms consistently demonstrated that SIR with
      the NLM-based regularization can achieve more gains than SIR with the well-known
      Gaussian MRF regularization or the generalized Gaussian MRF regularization and
      the conventional FBP method, in terms of image noise reduction and resolution
      preservation. 

PMID- 24881500
TI  - Influence of mammography screening on use of mastectomies in Denmark.

PMID- 24881499
TI  - Investigation of the reproducibility and reliability of sagittal vertebral
      inclination measurements from MR images of the spine.
AB  - In this study, sagittal vertebral inclination (SVI) was systematically evaluated
      for 28 vertebrae (segments between T4 and L5) in magnetic resonance (MR) images
      of one normal and one scoliotic subject to compare the performance of manual and
      computerized measurements, and identify the most reproducible and reliable
      measurements. Manual measurements were performed by three observers, who
      identified on two occasions the distinctive anatomical landmarks required to
      evaluate SVI by six measurement methods, i.e. the superior tangents, inferior
      tangents, anterior tangents, posterior tangents, mid-endplate lines and mid-wall
      lines. Computerized measurements were performed by automatically evaluating SVI
      from the symmetry of vertebral anatomical structures in two-dimensional (2D)
      sagittal cross-sections and in three-dimensional (3D) volumetric images. The mid
      wall lines and posterior tangents proved to be the manual measurements with the
      lowest intra-observer (standard deviation, SD, of 1.4 degrees  and 1.7 degrees ,
      respectively) and inter-observer variability (SD of 1.9 degrees  and 2.4 degrees
      , respectively). The strongest inter-method agreement was found between the mid
      wall lines and posterior tangents (SD of 2.0 degrees ). Computerized measurements
      in 2D and in 3D resulted in intra-observer (SD of 2.8 degrees  and 3.1 degrees ,
      respectively) and inter-observer variability (SD of 3.8 degrees  and 5.2 degrees
      , respectively) that were comparable to those of the superior tangents (SD of 2.6
      degrees  and 3.7 degrees ) and inferior tangents (SD of 3.2 degrees  and 4.5
      degrees ), which represent standard Cobb angle measurements. It can be concluded
      that computerized measurements of SVI should be based on the inclination of
      vertebral body walls. 

PMID- 24881501
TI  - Comments to the paper: Influence of mammography screening on use of mastectomies
      in Denmark.

PMID- 24881502
TI  - Functional morphology of mucosal goblet cells based on spatial separation of
      orifice openings to the surface--application to the rabbit bulbar conjunctiva.
AB  - The purpose of the study was to assess spatial separation of goblet cell orifices
      observed at the surface of the rabbit bulbar conjunctiva by scanning electron
      microscopy (SEM) specimens of the bulbar conjunctiva from 8 healthy pigmented
      rabbits were obtained using a special preparation technique by which the tissue
      was carefully stretched out during glutaraldehyde fixation. On high magnification
      prints of SEM images of the conjunctival surface, the locations of goblet cell
      openings (orifices) to the apical surface were marked and the centre-to-centre
      spacing between all such orifices measured. Across the regions of interest (ROI),
      with averaged dimensions of 322 MUm * 230 MUm (adjusted for tissue shrinkage),
      the averaged value for the distances between all orifices was 196 MUm (range 141
      241 MUm), with the calculated density of orifices being 412 mm(-2). A sequential
      order-based analysis of the spatial separation between orifices indicated a
      predictable value of 6 MUm, a separation that showed a nearly linear inter
      dependence over distances of at least 200 MUm. The openings of goblet cells to
      the surface of unstimulated bulbar conjunctiva have a organized spatial
      distribution that is consistent with there being an organized control of goblet
      cell secretion.

PMID- 24881503
TI  - The radiology report version 2.0.

PMID- 24881504
TI  - Doing poorly by doing good: the bottom line of proton therapy for children.
AB  - PURPOSE: Proton beam therapy (PBT) is the most expensive form of radiation
      therapy in the United States. An area in which clear advantage has been modeled
      is the use of PBT for pediatric patients, although no publications deal with
      practice costs to PBT centers associated with a pediatric focus. Pediatric cases
      require longer treatment times and more staff members and incur higher supply and
      device costs. In addition to being more expensive to treat, the pediatric
      patients at the authors' center also present with Medicaid as their primary
      insurer at higher rates than adults. At their center, in the past 2 years,
      pediatric patients (<21 years of age) have constituted 32% of total patients
      treated. The authors present their cost experience in a PBT environment treating
      a large number of children. METHODS: After approval was obtained from the local
      institutional review board, data relating to patients <=21 years of age who
      started treatment during the period between November 1, 2011, and October 31,
      2013, were reviewed. Direct expenses of devices and supplies used, billing for
      anesthesia, staffing, and direct operational costs (proton beam) were calculated
      to determine the direct cost to treat. Those direct costs were then compared with
      actual reimbursements received for those treatments. Additionally, gross
      operating costs per hour and gross average expenses per pediatric patient were
      calculated, and that cost was then compared with actual reimbursement. RESULTS:
      The mission to preferentially treat pediatric patients involves accepting a loss
      for one-third of pediatric patients before allocating any overhead. After
      averaging gross expenses over total operating hours, 60% of the pediatric
      patients were found to be treated at a net loss. CONCLUSIONS: Given insurance
      constraints and unique costs associated with the pediatric population, PBT
      centers devoted to children should not be expected to be markedly profitable. For
      centers that do choose to accept pediatric patients, those patients must be
      balanced with patients producing higher net reimbursement.

PMID- 24881505
TI  - Reducing radiation, revising reference levels.

PMID- 24881506
TI  - Surviving the dark night: the Aurora, Colorado, mass shootings.

PMID- 24881507
TI  - Mucormycosis attributed mortality: a seven-year review of surgical and medical
      management.
AB  - INTRODUCTION: Historically, mucormycosis infections have been associated with
      high mortality. The purpose of this study was to determine the incidence,
      associated mortality, and management strategies of mucormycosis in a major burn
      center. METHODS: A retrospective review was performed via obtaining all patients
      with mucormycosis admitted from January 2003 to November 2009 at our adult burn
      center was performed obtaining demographic data relevant to fungal burn wound
      infection or colonization. RESULTS: The incidence of mucormycosis at our facility
      was 4.9 per 1000 admissions; specifically, 11 military casualties and one
      civilian were diagnosed with mucormycosis. The median percentage Total Body
      Surface Area (TBSA) burned, 11 patients, or open wound, one patient, was 60 (IQR,
      54.1-80.0), and the incidence of documented inhalation injury was 66.7% (8 of
      12). Ten patients had surgical amputations. A median of eight days (IQR, 3.5
      74.5) elapsed from diagnosis of mucormycosis until death in the 11 patients who
      expired. The overall mortality was 92%; however, autopsy attributed mucormycosis
      mortality was 54.5% (6 of 11) with all six patients having invasive mucormycosis.
      CONCLUSION: Aggressive surgical intervention should be undertaken for invasive
      mucormycosis; additionally, implementation of standardized protocols for patients
      with large soft tissue injuries may mitigate mucormycosis superimposition.

PMID- 24881508
TI  - Antitumour effect and modulation of expression of the ABCB1 gene by perifosine in
      canine lymphoid tumour cell lines.
AB  - Acquisition of multidrug resistance (MDR) is a common cause of treatment failure
      during chemotherapy for dogs with lymphoma (lymphosarcoma). Overexpression of P
      glycoprotein (P-gp), encoded by the ABCB1 gene, is associated with MDR.
      Perifosine, an Akt inhibitor, downregulates the expression of P-gp. In this
      study, the antitumour effect of perifosine and its ability to modulate ABCB1
      expression were examined in four canine lymphoid tumour cell lines (GL-1, CLBL-1,
      UL-1 and Ema). GL-1 and CLBL-1 were inherently negative for P-gp, while UL-1 and
      Ema were inherently positive for P-gp. GL-1 and UL-1 were sensitive to
      perifosine, whereas CLBL-1 and Ema were resistant. The amount of ABCB1 mRNA
      significantly decreased after treatment with perifosine in UL-1, associated with
      activation of the c-Jun NH2-terminal kinase (JNK) pathway, but such an effect was
      not observed in Ema. In UL-1, perifosine decreased the efflux of rhodamine 123
      dye and reduced the 50% inhibitory concentration of vincristine, but such effects
      were not observed in Ema. Perifosine had an antitumour effect in 2/4 canine
      lymphoid tumour cell lines. In 1/4 cell lines, perifosine downregulated ABCB1
      gene expression through activation of the JNK pathway and increased sensitivity
      to vincristine.

PMID- 24881509
TI  - Ground reaction force adaptations to tripedal locomotion in dogs.
AB  - To gain insight into the adaptive mechanisms to tripedal locomotion and increase
      understanding of the biomechanical consequences of limb amputation, this study
      investigated kinetic and temporal gait parameters in dogs before and after the
      loss of a hindlimb was simulated. Nine clinically sound Beagle dogs trotted on an
      instrumented treadmill and the ground reaction forces as well as the footfall
      patterns were compared between quadrupedal and tripedal locomotion. Stride and
      stance durations decreased significantly in all limbs when the dogs ambulated
      tripedally, while relative stance duration increased. Both vertical and
      craniocaudal forces were significantly different in the remaining hindlimb. In
      the forelimbs, propulsive force increased in the contralateral and decreased in
      the ipsilateral limb, while the vertical forces were unchanged (except for mean
      force in the contralateral limb). Bodyweight was shifted to the contralateral and
      cranial body side so that each limb bore ~33% of the dog's bodyweight. The
      observed changes in the craniocaudal forces and the vertical impulse ratio
      between the fore- and hindlimbs suggest that a nose-up pitching moment occurs
      during the affected limb pair's functional step. To regain pitch balance for a
      given stride cycle, a nose-down pitching moment is exerted when the intact limb
      pair supports the body. These kinetic changes indicate a compensatory mechanism
      in which the unaffected diagonal limb pair is involved. Therefore, the intact
      support pair of limbs should be monitored closely in canine hindlimb amputees.

PMID- 24881510
TI  - One Health: the importance of education and the impact of interprofessional
      interventions.

PMID- 24881511
TI  - Measuring the response to therapeutic foot trimming in dairy cows with
      fortnightly lameness scoring.
AB  - Lameness scoring (0-3) was carried out on four UK dairy farms during the housing
      period over three consecutive years (2010-2012). At the start of the study cows
      were matched by parity and stage of lactation and randomly allocated into a
      treatment (TX) and a control (CX) group. Cows were enrolled when two sound scores
      (0 or 1) were followed by a lame score (2). Farmers were immediately notified of
      score 3 cows, which were then excluded from the study, irrespective of whether
      they were in treatment or control groups. The animals in the TX group received
      treatment 3-48 h after being scored lame. Farmers remained blind to the treatment
      group. Throughout the study the participating farmers continued to identify and
      treat lame cows according to their usual approaches, this included treating
      animals in the CX or TX group if they so chose. The fortnightly lameness scoring
      and treatment of the TX group resulted in higher cure rates at each scoring
      session following treatment when compared with the CX group (P < 0.001). Two
      weeks after inclusion, 78% (SE  +/-  3.2) of TX cows were sound, compared with
      66% (SE  +/-  3.1) of CX cows. At 18  weeks following initial recruitment this
      had fallen to 41% (SE  +/-  6.3) (TX) and 13% (SE  +/-  4.7) (CX). The percentage
      of total scores which were sound scores in the TX and CX groups following
      inclusion in the trial was 81% and 66.1%, respectively (P < 0.001). The main
      lesions found on treatment in the TX group were sole haemorrhage (41% of cases)
      and digital dermatitis (33%). Severe lesions (sole ulcers and toe necrosis) were
      only found in 6.6% of cases. In the treated CX animals the percentage of severe
      lesions was 14%.

PMID- 24881512
TI  - Factors associated with Culicoides Obsoletus complex spp.-specific IgE reactivity
      in Icelandic horses and Shetland ponies.
AB  - Insect bite hypersensitivity (IBH) is a common allergic skin disease in horses,
      caused by biting insects of the Culicoides spp. In The Netherlands, Culicoides
      spp. of the Obsoletus complex are the most important midges involved in IBH. The
      aim of the present study was to identify and quantify associations between
      several endogenous (host) and exogenous (environmental) factors and
      immunoglobulin E (IgE) reactivity against Obsoletus complex-derived whole body
      extract or seven recombinant allergens, measured by ELISA. Data from 143
      Icelandic horses and 177 Shetland ponies were analysed using multivariable
      models. In addition, the relationship between IgE reactivity and severity of
      clinical signs in IBH-affected horses was examined. Positive correlations were
      found between Obsoletus complex-specific IgE and severity of clinical signs.
      Disease status (IBH affected or control), breed and the interaction between IBH
      status and breed were significantly associated with IgE reactivity against
      several Obsoletus complex allergens. Significantly greater IgE reactivity was
      seen in IBH-affected horses compared to controls. The differences in IgE values
      between cases and controls were most pronounced in Icelandic horses. Shetland
      pony controls had significantly greater IgE reactivity compared to Icelandic
      horse controls, while differences in IgE values comparing Shetland pony cases and
      Icelandic horse cases were not significant. Severity of clinical signs and IgE
      reactivity in IBH-affected horses against several Obsoletus complex allergens
      appeared to be related. Consideration of the factors associated with Obsoletus
      complex-specific IgE in horses might further improve interpretation and accuracy
      of IgE ELISA test results within these breeds, although further research is
      required.

PMID- 24881513
TI  - Short term effects of increasing dietary salt concentrations on urine composition
      in healthy cats.
AB  - High dietary salt (NaCl) concentrations are assumed to be beneficial in
      preventing the formation of calcium oxalate (CaOx) uroliths in cats, since
      increased water intake and urine volume have been observed subsequent to intake.
      In human beings, dietary NaCl restriction is recommended for the prevention of
      CaOx urolith formation, since high NaCl intake is associated with increased
      urinary Ca excretion. The aim of the present study was to clarify the role of
      dietary NaCl in the formation of CaOx uroliths in cats. Eight cats received four
      diets that differed in Na and Cl concentrations (0.38-1.43% Na and 0.56-2.52% Cl
      dry matter, DM). Each feeding period consisted of a 21 day adaptation period,
      followed by a 7 day sampling period for urine collection. Higher dietary NaCl
      concentrations were associated with increased urine volume and renal Na
      excretion. Urinary Ca concentration was constant, but renal Ca excretion
      increased from 0.62 to 1.05 mg/kg bodyweight (BW)/day with higher dietary NaCl
      concentrations (P <= 0.05). Urinary oxalate (Ox), citrate, P and K concentrations
      decreased when NaCl intake was high (P <= 0.05), and urinary pH was low in all
      groups (6.33-6.45; P > 0.05). Relative supersaturation of CaOx in the urine was
      unaffected by dietary NaCl concentrations. In conclusion, the present study
      demonstrated several beneficial effects of high dietary NaCl intake over a
      relatively short time period. In particular, urinary Ca concentration remained
      unchanged because of increased urine volume. Decreased urinary Ox concentrations
      might help to prevent the formation of CaOx uroliths, but this should be verified
      in future studies in diseased or predisposed cats. 

PMID- 24881514
TI  - Hospital variation in risk-standardized hospital admission rates from US EDs
      among adults.
AB  - BACKGROUND: Variation in hospital admission rates of patients presenting to the
      emergency department (ED) may represent an opportunity to improve practice. We
      seek to describe national variation in hospital admission rates from the ED and
      to determine the degree to which variation is not explained by patient
      characteristics or hospital factors. METHODS: We conducted a cross-sectional
      analysis of a nationally representative sample of ED visits among adults within
      the 2010 National Hospital Ambulatory Care Survey ED data of hospitals with
      admission rates from the ED between 5% and 50%. We calculated risk-standardized
      hospital admission rates (RSARs) from the ED using contemporary hospital
      profiling methodology, accounting for patients' sociodemographic and clinical
      characteristics. RESULTS: Among 19831 adult ED visits in 252 hospitals, there
      were 4148 hospital admissions from the ED. After accounting for patients'
      sociodemographic and clinical factors, the median RSAR from the ED was 16.9%
      (interquartile range, 15.0%-20.4%), and 8.1% of the variation in RSARs was
      attributable to an institution-specific effect. Even after accounting for
      hospital teaching status, ownership, urban/rural location, and geographical
      location, 7.0% of the variation in RSARs from the ED was still attributable to an
      institution-specific effect. CONCLUSIONS AND RELEVANCE: There was variation in
      hospital admission rates from the ED in the United States, even after adjusting
      for patients' sociodemographic and clinical characteristics and accounting for
      hospital factors. Our findings suggest that suggesting that the likelihood of
      being admitted from the ED is not only dependent on clinical factors but also at
      which hospital the patient seeks care.

PMID- 24881515
TI  - A misdiagnosis of clonorchiasis as gallstone, leading to an unnecessary
      cholecystectomy: a case report.
AB  - This case report describes an unusual presentation of Clonorchissinensis
      infection. In this rare case, a clonorchiasis infection that had been latent for
      decades was misdiagnosed as acute calculous cholecystitis.Exploratory surgery and
      a cholecystectomy were performed. Therefore,in the course of diagnosis of hepatic
      and gall diseases, we cannot neglect parasite infections such as clonorchiasis.

PMID- 24881516
TI  - Life-threatening hemothorax due to azygos vein rupture after chest compression
      during cardiopulmonary resuscitation.
AB  - Hemothorax is not an uncommon cardiopulmonary resuscitation(CPR)-related
      complication. But hemothorax related to azygos vein injury (AVI) is a rare
      condition following blunt chest trauma, with no report of CPR-related AVI in the
      literature. We present a case of azygosve in rupture in a middle-aged woman after
      repeated chest compression during 1 hour of CPR. She eventually presented with
      massive hemothorax due to azygos vein rupture diagnosed by computed tomography
      (CT). When faced with a patient with massive hemothorax after chest compression,
      azygos vein rupture should be considered as a complication.

PMID- 24881517
TI  - Good outcome after intravenous thrombolysis for acute stroke in a patient under
      treatment with dabigatran.
AB  - The novel oral anticoagulants (NOACs) are indicated for stroke and systemic
      embolism prophylaxis in patients with nonvalvular atrial fibrillation (AF). Very
      few cases of intravenous recombinant tissue plasminogen activator (IV rt-PA) in
      patients under treatment with NOACs have been described. The decision to
      thrombolyze patients under NOACs is complex and requires a balance between the
      benefits of treatment and the risk of symptomatic hemorrhagic complications.We
      describe an unusual case of treatment IV rt-PA for acute ischemic stroke in a
      patient receiving dabigatran for AF. The decision to treat the patient with IV rt
      PA was based on the combination of normal coagulation times with the long time
      elapsed after the last dose of dabigatran, when the drug effect was predictably
      residual.

PMID- 24881518
TI  - Oral administration of D-aspartate, but not L-aspartate, depresses rectal
      temperature and alters plasma metabolites in chicks.
AB  - AIMS: L-Aspartate (L-Asp) and D-aspartate (D-Asp) are physiologically important
      amino acids in mammals and birds. However, the functions of these amino acids
      have not yet been fully understood. In this study, we therefore examined the
      effects of L-Asp and D-Asp in terms of regulating body temperature, plasma
      metabolites and catecholamines in chicks. MAIN METHODS: Chicks were first orally
      administered with different doses (0, 3.75, 7.5 and 15 mmol/kg body weight) of L-
      or D-Asp to monitor the effects of these amino acids on rectal temperature during
      120 min of the experimental period. KEY FINDINGS: Oral administration of D-Asp,
      but not of L-Asp, linearly decreased the rectal temperature in chicks.
      Importantly, orally administered D-Asp led to a significant reduction in body
      temperature in chicks even under high ambient temperature (HT) conditions.
      However, centrally administered D-Asp did not significantly influence the body
      temperature in chicks. As for plasma metabolites and catecholamines, orally
      administered D-Asp led to decreased triacylglycerol and uric acid concentrations
      and increased glucose and chlorine concentrations but did not alter plasma
      catecholamines. SIGNIFICANCE: These results suggest that oral administration of D
      Asp may play a potent role in reducing body temperature under both normal and HT
      conditions. The alteration of plasma metabolites further indicates that D-Asp may
      contribute to the regulation of metabolic activity in chicks.

PMID- 24881519
TI  - The hepatocyte phase of Gd-EOB-DTPA-enhanced MRI in the evaluation of hepatic
      fibrosis and early liver cirrhosis in a rat model: an experimental study.
AB  - AIMS: To evaluate the hepatocyte phase of Gd-EOB-DTPA-enhanced MRI in the early
      diagnosis of hepatic fibrosis and cirrhosis and assessment of liver function in a
      rat model. MAIN METHODS: In 2 groups of SD rats, liver fibrosis was induced in
      experimental animals by repetitive carbon tetrachloride injections, while the
      control group received saline injections. Five experimental rats and 2 control
      rats were randomly selected at weeks 4, 8, 12. One week after carbon
      tetrachloride administration, MRI (FIRM T1WI) scan was performed. Gd-EOB-DTPA
      (0.08mL) was injected into the rat's tail vein and hepatocyte phase images were
      obtained after 20min. The pre-enhanced phase and hepatocyte phase signal
      intensities (SI) were measured, and the relative contrast enhancement index
      (RCEI) was calculated. ANOVA analysis (LSD) of RCEI values in controls (n=6),
      hepatic fibrosis (n=7), and histopathologically-determined early cirrhosis group
      (n=6) was performed. KEY FINDINGS: RECI values showed a decreasing trend in the
      control group, hepatic fibrosis and early cirrhosis groups (1.11+/-0.43, 0.96+/
      0.22, and 0.57+/-0.33, respectively). While the difference between the control
      and early cirrhosis groups was statistically significant (p=0.013), there was no
      significant difference in the hepatic fibrosis group vs the control (p=0.416) and
      the hepatic fibrosis group vs the early cirrhosis group (p=0.054). SIGNIFICANCE:
      Hepatocyte phase RCEI values obtained with Gd-EOB-DTPA-enhanced MRI scan indicate
      liver injury in hepatic fibrosis and early cirrhosis. RCEI values are helpful for
      early diagnosis of liver cirrhosis.

PMID- 24881520
TI  - Responsive polymer-fluorescent carbon nanoparticle hybrid nanogels for optical
      temperature sensing, near-infrared light-responsive drug release, and tumor cell
      imaging.
AB  - Fluorescent carbon nanoparticles (FCNPs) have been successfully immobilized into
      poly(N-isopropylacrylamide-co-acrylamide) [poly(NIPAM-AAm)] nanogels based on one
      pot precipitation copolymerization of NIPAM monomers with hydrogen bonded FCNP
      AAm complex monomers in water. The resultant poly(NIPAM-AAm)-FCNP hybrid nanogels
      can combine functions from each building block for fluorescent temperature
      sensing, cell imaging, and near-infrared (NIR) light responsive drug delivery.
      The FCNPs in the hybrid nanogels not only emit bright and stable
      photoluminescence (PL) and exhibit up-conversion PL properties, but also increase
      the loading capacity of the nanogels for curcumin drug molecules. The reversible
      thermo-responsive swelling/shrinking transition of the poly(NIPAM-AAm) nanogel
      can not only modify the physicochemical environment of the FCNPs to manipulate
      the PL intensity for sensing the environmental temperature change, but also
      regulate the releasing rate of the loaded anticancer drug. In addition, the FCNPs
      embedded in the nanogels can convert the NIR light to heat, thus an exogenous NIR
      irradiation can further accelerate the drug release and enhance the therapeutic
      efficacy. The hybrid nanogels can overcome cellular barriers to enter the
      intracellular region and light up the mouse melanoma B16F10 cells upon laser
      excitation. The demonstrated hybrid nanogels with nontoxic and optically active
      FCNPs immobilized in responsive polymer nanogels are promising for the
      development of a new generation of multifunctional materials for biomedical
      applications. 

PMID- 24881521
TI  - Stopping the revolving door: effectiveness of mental health court in reducing
      recidivism by mentally ill offenders.
AB  - OBJECTIVES: This study compared recidivism outcomes among criminal offenders with
      mental illness who were assigned to a mental health court (MHC) or a traditional
      criminal court. It also explored potential differences in outcomes between
      subgroups of offenders, including felony and misdemeanor offenders and violent
      and nonviolent offenders. METHODS: Data were obtained from court databases.
      Offenders in the MHC (N=198) and the traditional criminal court (N=198) were
      matched by propensity scores and followed for 12 months after the index offense.
      Data for the 12 months preceding the index offense were obtained for MHC
      participants. Intent-to-treat analyses were conducted, using both between-group
      and within-subjects designs. RESULTS: After control for covariates, logistic and
      Cox regressions indicated that MHC assignment predicted a lower overall rate of
      recidivism and longer time to rearrest for a new charge compared with assignment
      to traditional court. The groups did not significantly differ on the severity of
      the offense associated with rearrest. The findings largely held for felony,
      misdemeanor, violent, and nonviolent offenders, with the exception of analyses
      involving time to rearrest for violent offenders. Within-subjects analyses
      suggested that after MHC participation, there were improvements in occurrence of
      rearrest and time to rearrest but a tendency for rearrest to be associated with
      more severe offenses. Within the MHC group, recidivism outcomes did not
      significantly differ by class of offense. CONCLUSIONS: The results suggest that
      an MHC can be effective in reducing recidivism among offenders with mental
      illness and also indicate that persons who commit more severe offenses may be
      appropriate candidates for MHC.

PMID- 24881522
TI  - Blockade of renin-angiotensin system prevents micturition dysfunction in
      renovascular hypertensive rats.
AB  - Association between hypertension and bladder symptoms has been described. We
      hypothesized that micturition dysfunction may be associated with renin
      angiotensin system (RAS) acting in urethra. The effects of the anti-hypertensive
      drugs losartan (AT1 antagonist) and captopril (angiotensin-converting enzyme
      inhibitor) in comparison with atenolol (beta1-adrenoceptor antagonist
      independently of RAS blockade) have been investigated in bladder and urethral
      dysfunctions during renovascular hypertension in rats. Two kidney-1 clip (2K-1C)
      rats were treated with losartan (30 mg/kg/day), captopril (50mg/kg/day) or
      atenolol (90 mg/kg/day) for eight weeks. Cystometric study, bladder and urethra
      smooth muscle reactivities, measurement of cAMP levels and p38 MAPK
      phosphorylation in urinary tract were determined. Losartan and captopril markedly
      reduced blood pressure in 2K-1C rats. The increases in non-voiding contractions,
      voiding frequency and bladder capacity in 2K-1C rats were prevented by treatments
      with both drugs. Likewise, losartan and captopril prevented the enhanced bladder
      contractions to electrical-field stimulation (EFS) and carbachol, along with the
      impaired relaxations to beta-adrenergic-cAMP stimulation. Enhanced neurogenic
      contractions and impaired nitrergic relaxations were observed in urethra from 2K
      1C rats. Angiotensin II also produced greater urethral contractions that were
      accompanied by higher phosphorylation of p38 MAPK in urethral tissues of 2K-1C
      rats. Losartan and captopril normalized the urethral dysfunctions in 2K-1C rats.
      In contrast, atenolol treatment largely reduced the blood pressure in 2K-1C rats
      but failed to affect the urinary tract smooth muscle dysfunction. The urinary
      tract smooth muscle dysfunction in 2K-1C rats takes place by local RAS activation
      irrespective of levels of arterial blood pressure.

PMID- 24881523
TI  - Sleep quality and stress in women with pregnancy-induced hypertension and
      gestational diabetes mellitus.
AB  - BACKGROUND: Pregnant women with complications including pregnancy-induced
      hypertension (PIH) and gestational diabetes mellitus (GDM) often experience
      disrupted sleep patterns because of activation of the sympathetic nervous system.
      These pathologies are aggravated by sympathetic nervous system activation and may
      be related to stress. The present study aimed to clarify the characteristics of
      and changes in sleep quality and stress in pregnant women with PIH and GDM during
      the second and third trimesters. METHODS: We enrolled 56 women in their second or
      third trimesters who were diagnosed with PIH or GDM. Participants completed
      questionnaires, including the Pittsburgh Sleep Quality Index (PSQI) and the
      Perceived Stress Scale (PSS). Secretory immunoglobulin A (SlgA) concentrations
      were measured as a biological indicator of stress. RESULTS: PSS scores and
      subjective stress parameters were significantly higher than those reported from
      previous studies of healthy pregnant women (15.2 points and 15.1 points for the
      second and third trimesters, respectively). Mean one-day values for SIgA were
      168.3 and 205.7 MUg/mL for the second and third trimesters, respectively. During
      the second and third trimesters, SIgA scores were higher than those reported for
      healthy pregnant women in previous studies. The PSQI component scores sleep
      disturbance (C5) and sleep duration (C3) in follow up case were significantly
      higher in the third trimester than in the second trimester. DISCUSSION: This
      investigation suggests that pregnant women with PIH and GDM experience higher
      stress levels than do non-pregnant women and healthy pregnant women. Further, our
      results indicate that sleep quality worsens during the third trimester compared
      with the second trimester.

PMID- 24881524
TI  - Informing maternity service development by surveying new mothers about
      preferences for nutrition education during their pregnancy in an area of social
      disadvantage.
AB  - BACKGROUND: A demonstrated link exists between maternal diet and maternal and
      infant health outcomes during and after pregnancy. A dietetic maternity service
      (0.6FTE for 3500 births) was introduced in 2012 at our hospital in a socially
      disadvantaged area. We needed to develop evidence-based, patient-oriented
      improvements to nutrition services within resource limitations. AIM: This cross
      sectional study gathered knowledge, eating behaviours, and nutrition-related
      needs of our women ante- and postnatally to inform this process. METHODS: Women
      (>= 18 years) admitted to the postnatal ward completed our survey. Data including
      dietary quality, nutritional knowledge and interest in nutrition education were
      collected. Analysis included descriptive, chi-squared and t-tests. FINDINGS:
      Three hundred and nine eligible women responded (28 +/- 6 years, 27 +/- 7 kg/m(2)
      pre-pregnancy body mass index, 12% gestational diabetes). Two-fifths (42%) self
      reported gaining excess weight during pregnancy. One quarter reported knowing
      their gestational weight gain goals, yet only 1.6% was correct. Half reported
      interest in receiving nutrition education during pregnancy and post-delivery
      (45%, n=134; 43%, n=123, respectively). Women had poor diet quality (daily serves
      - fruit: 1.8 +/- 1.0; vegetables: 2.0 +/- 1.2; dairy: 1.9 +/- 1.2), despite
      identifying healthy eating as a personal priority. Nutrition topics requested
      included healthy eating for development of baby pre- and post-delivery and
      maternal weight management. CONCLUSION: Women attending our hospital have dietary
      issues and levels of interest in nutrition similar to women in tertiary maternity
      centres. Service changes planned will explore formats that meet higher and lower
      education levels; group workshops may be supplemented by formats such as internet
      and DVD-delivered education to overcome access and literacy issues, respectively.

PMID- 24881525
TI  - Infectious causes of stroke.
AB  - Most infectious pathogens have anecdotal evidence to support a link with stroke,
      but certain pathogens have more robust associations, in which causation is
      probable. Few dedicated prospective studies of stroke in the setting of infection
      have been done. The use of head imaging, a clinical standard of diagnostic care,
      to confirm stroke and stroke type is not universal. Data for stroke are scarce in
      locations where infections are probably most common, making it difficult to reach
      conclusions on how populations differ in terms of risk of infectious stroke. The
      treatment of infections and stroke, when concomitant, is based on almost no
      evidence and requires dedicated efforts to understand variations that might
      exist. We highlight the present knowledge and emphasise the need for stronger
      evidence to assist in the diagnosis, treatment, and secondary prevention of
      stroke in patients in whom an infectious cause for stroke is probable. 

PMID- 24881526
TI  - Effect of HIFU treatment on tumor targeting efficacy of docetaxel-loaded Pluronic
      nanoparticles.
AB  - Numerous studies have been performed to identify the microenvironment of solid
      tumors, which is responsible for the insufficient delivery of anticancer drugs to
      tumor cells due to the poorly organized vasculature and the increased
      interstitial fluid pressure. As a result, the extravasation of convection
      dependent agents including NPs is severely limited. Therefore, we have
      demonstrated the feasibility of targeting an enhancement of docetaxel-loaded
      Pluronic nanoparticles (NPs) using high-intensity focused ultrasound (HIFU) as an
      external stimulus-induced clinical system in tumor tissue. The efficient
      extravasation of NPs into the interior cells in tumor tissue was induced by
      relatively low HIFU exposure without apparent acute tissue damage. The enhanced
      targeting of NPs with near-infrared fluorescence dye was observed in tumor
      bearing mice with various HIFU exposures. As a result, the greatest accumulation
      of NPs at the tumor tissue was observed at an HIFU exposure of 20 W/cm(2).
      However, the tumor tissue above at 20 W/cm(2) appeared to be destroyed and the
      tumor targetability of NPs was significantly decreased owing to thermal ablation
      with necrosis, resulting in the destruction of the tumor tissue and the blood
      vessels. In particular, a cross-sectional view of the tumor tissue verified that
      the NPs migrated into the middle of the tumor tissue upon HIFU exposure. The
      preliminary results here demonstrate that HIFU exposure through non-thermal
      mechanisms can aid with the extravasation of NPs into the interior cells of
      tumors and increase the therapeutic effect in enhanced and targeted cancer
      therapy.

PMID- 24881527
TI  - Low temperature hydrogen plasma assisted chemical vapor generation for Atomic
      Fluorescence Spectrometry.
AB  - Chemical vapor generation techniques have long been considered as important ways
      of sample introduction for analytical atomic spectrometry. In this paper, a low
      temperature plasma assisted chemical vapor generation method which avoids the
      massive use of consumptive chemical agents was proposed by using atmospheric
      pressure dielectric barrier discharge. The plasma was generated by hydrogen doped
      argon gas flow through a quartz tube, serving as a dielectric barrier, which had
      a copper wire inner electrode and a copper foil outer electrode. An alternative
      high voltage was applied to electrodes to ignite and sustain the plasma. Sample
      solutions were converted to aerosol by a nebulizer and then mixed with the plasma
      to generate hydrides. To confirm the utility of this method, four hydride forming
      elements, As, Te, Sb and Se, were determined by coupling the low temperature
      plasma assisted chemical vapor generation system with an atomic fluorescence
      spectrometer. Responses of As, Te, Sb and Se were linear in the range of 0.5
      20MUg mL(-1). The RSDs of As, Te, Sb and Se in the present method were less than
      4.1% and the absolute detection limits for As, Te, Sb and Se were 0.6ng, 1.0ng,
      1.4ng and 1.2ng, respectively. Furthermore, four arsenic species were determined
      after HPLC separation. The method is green and simple compared with hydride
      generation with tetrahydroborate and the most attractive characteristic is micro
      sampling. In principle, the method offers potential advantages of
      miniaturization, less consumption and ease of automation.

PMID- 24881528
TI  - Determination of tributyltin in environmental water matrices using stir bar
      sorptive extraction with in-situ derivatisation and large volume injection-gas
      chromatography-mass spectrometry.
AB  - Stir bar sorptive extraction with in-situ derivatization using sodium
      tetrahydridoborate (NaBH4) followed by liquid desorption and large volume
      injection-gas chromatography-mass spectrometry detection under the selected ion
      monitoring mode (SBSE(NaBH4)in-situ-LD/LVI-GC-MS(SIM)) was successfully developed
      for the determination of tributyltin (TBT) in environmental water matrices. NaBH4
      proved to be an effective and easy in-situ speciation agent for TBT in aqueous
      media, allowing the formation of adducts with enough stability and suitable
      polarity for SBSE analysis. Assays performed on water samples spiked at the
      10.0MUg/L, yielded convenient recoveries (68.2+/-3.0%), showed good accuracy,
      suitable precision (RSD<9.0%), low detection limits (23ng/L) and excellent linear
      dynamic range (r(2)=0.9999) from 0.1 to 170.0ug/L, under optimized experimental
      conditions. By using the standard addition method, the application of the present
      methodology to real surface water samples allowed very good performance at the
      trace level. The proposed methodology proved to be a feasible alternative for
      routine quality control analysis, easy to implement, reliable and sensitive to
      monitor TBT in environmental water matrices. 

PMID- 24881529
TI  - The analysis of estrogenic compounds by flow injection analysis with amperometric
      detection using a boron-doped diamond electrode.
AB  - We report on the use of flow injection analysis with amperometric detection (FIA
      EC) to evaluate the potential of using diamond electrodes for the analysis of
      three estrogenic compounds: estrone, 17-beta-estradiol, and estriol. Amperometric
      detection was performed using a cathodically pretreated boron-doped diamond
      electrode that offered low background current, relatively low limits of
      detection, and good response reproducibility and stability. For all three
      compounds, response linearity was observed over the concentration range tested,
      0.10 to 3.0MUmol L(-1), the sensitivity was ca. 10mA L mol(-1), and the minimum
      concentration detection (S/N>=3) was 0.10MUmol L(-1) (~27MUg L(-1)). The response
      variability with multiple injections was ca. 10% (RSD) over 20 injections. For
      estrone, the oxidation reaction on diamond does not proceed through an adsorbed
      state like it does on glassy carbon. After an initial current attenuation, the
      diamond electrode exhibited a stable response (oxidation current) for 3 days of
      continuous use, indicative of minimal surface contamination or fouling by
      reaction intermediates and products. The method for estrone was assessed using
      spiked city tap and local river water. Estrone recoveries in spiked city and
      river water samples presented standard deviations of less than 10%. In summary,
      the FIA-EC method with a diamond electrode enables sensitive, reproducible,
      stable, quick, and inexpensive determination of estrogenic compounds in water
      samples.

PMID- 24881530
TI  - A novel functionalisation process for glucose oxidase immobilisation in
      poly(methyl methacrylate) microchannels in a flow system for amperometric
      determinations.
AB  - Different materials like glass, silicon and poly(methyl methacrylate) (PMMA) are
      being used to immobilise enzymes in microchannels. PMMA shows advantages such as
      its low price, biocompatibility and attractive mechanical and chemical
      properties. Despite this, the introduction of reactive functional groups on PMMA
      is still problematic, either because of the complex chemistry or extended
      reaction time involved. In this paper, a new methodology was developed to
      immobilise glucose oxidase (GOx) in PMMA microchannels, with the benefit of a
      rapid immobilisation process and a very simple route. The new procedure involves
      only two steps, based on the reaction of 5.0% (w/w) polyethyleneimine (PEI) with
      PMMA in a dimethyl sulphoxide medium, followed by the immobilisation of glucose
      oxidase using a solution containing 100U enzymes and 1.0% (v/v) glutaraldehyde.
      The reactors prepared in this way were evaluated by a flowing system with
      amperometric detection (+0.60V) based on the oxidation of the H2O2 produced by
      the reactor. The microreactor proposed here was able to work with high
      bioconversion and a frequency of 60 samples h(-1), with detection and
      quantification limits of 0.50 and 1.66umol L(-1), respectively. Michaelis-Menten
      parameters (Vmax and KM) were calculated as 449+/-47.7nmol min(-1) and 7.79+/
      0.98mmol. Statistical evaluations were done to validate the proposed methodology.
      The content of glucose in natural and commercial coconut water samples was
      evaluated using the developed method. Comparison with spectrophotometric
      measurements showed that both methodologies have a very good correlation
      (tcalculated, 0.05, 4=1.35<ttabled, 0.05, 4=2.78).

PMID- 24881531
TI  - Graphene coated silica applied for high ionization matrix assisted laser
      desorption/ionization mass spectrometry: A novel approach for environmental and
      biomolecule analysis.
AB  - The integration of nanotechnology with mass spectrometry for sensitive and
      selective detection of molecules is a hot/important field of research. Synthesis
      of graphene (G) coated with mesoporous silica (SiO2, G@SiO2) for mass
      spectrometric application has been demonstrated. For the first time, we proposed
      the significant role of surfactant that used during the synthesis of mesorporous
      silicate (SiO2) in mass spectrometry. It was noticed that G could initiate SiO2
      via surfactants which work as initiators for further ionization. The porosity of
      SiO2 trapped the analytes that was released and ionized with the surfactant
      fragments. Undoubtedly, strong background interferences were present in the case
      of organic matrix, which greatly obscured the detection of low molecular weight
      compounds. G@SiO2 nanocomposite affords several advantages, such as the ability
      to detect small molecules (<500Da), high sample localization through silica
      mesoporosity, and high ionization efficiency over than G or conventional
      matrices. The high performance of G@SiO2 is not only due to the large surface
      area but also due to high desorption/ionization efficiency of inevitably
      surfactant (cetyltrimethylammonium chloride, CATB). Unlike the conventional MALDI
      MS, the G@SiO2-MS is capable of generating multiply charged polysaccharides. The
      present method was validated to detect surfactants with low limits of detection. 

PMID- 24881532
TI  - Study of the voltammetric behavior of jatrorrhizine and its sensitive
      determination at electrochemical pretreatment glassy carbon electrode.
AB  - A simple, inexpensive and highly sensitive electrochemical method for the
      determination of jatrorrhizine was developed using an electrochemically
      pretreated glassy carbon electrode (EPGCE). The electrochemical behavior of
      jatrorrhizine was systematically investigated in detail and some kinetic
      parameters were calculated for the first time. A reasonable reaction mechanism of
      jatrorrhizine on the EPGCE was also discussed and proposed, which could be a
      reference for the pharmacological action of jatrorrhizine in clinical study. And
      the first electroanalytical method of jatrorrhizine was established with a wide
      linear range from 7.0*10(-8) to 2.0*10(-5)mol L(-1) and a low detection limit of
      5.0*10(-8)mol L(-1). The proposed method was successfully applied in
      determination of jatrorrhizine in pharmaceutical sample, Tinospora capillipes
      Gagnep (a traditional Chinese medicine), with satisfactory results.

PMID- 24881533
TI  - Correlation of sensory bitterness in dairy protein hydrolysates: Comparison of
      prediction models built using sensory, chromatographic and electronic tongue
      data.
AB  - Sensory evaluation can be problematic for ingredients with a bitter taste during
      research and development phase of new food products. In this study, 19 dairy
      protein hydrolysates (DPH) were analysed by an electronic tongue and their
      physicochemical characteristics, the data obtained from these methods were
      correlated with their bitterness intensity as scored by a trained sensory panel
      and each model was also assessed by its predictive capabilities. The
      physiochemical characteristics of the DPHs investigated were degree of hydrolysis
      (DH%), and data relating to peptide size and relative hydrophobicity from size
      exclusion chromatography (SEC) and reverse phase (RP) HPLC. Partial least square
      regression (PLS) was used to construct the prediction models. All PLS regressions
      had good correlations (0.78 to 0.93) with the strongest being the combination of
      data obtained from SEC and RP HPLC. However, the PLS with the strongest
      predictive power was based on the e-tongue which had the PLS regression with the
      lowest root mean predicted residual error sum of squares (PRESS) in the study.
      The results show that the PLS models constructed with the e-tongue and the
      combination of SEC and RP-HPLC has potential to be used for prediction of
      bitterness and thus reducing the reliance on sensory analysis in DPHs for future
      food research. 

PMID- 24881534
TI  - Covalent modification of glassy carbon spheres through ball milling under solvent
      free conditions: A novel electrochemical interface for mercury(II)
      quantification.
AB  - A simple and green chemistry protocol has been proposed based on the covalent
      anchoring of benzamide molecule on glassy carbon spheres through ball milling
      under solvent free condition. The modification proceeds through the formation of
      an amide bond between carboxylic group of glassy carbon spheres and the amino
      group of modifier molecule. The formation of covalent bond was ascertained using
      X-ray photoelectron spectroscopy. Scanning electron microscopy was used to study
      the surface morphology of milled glassy carbon spheres. The aqueous colloidal
      solution of modified glassy carbon spheres was used in the preparation of thin
      film electrodes and subsequently used as a novel electrochemical interface in the
      quantification of mercury at trace level using a differential pulse anodic
      stripping voltammetric technique. The modified electrode showed good sensitivity
      and selectivity towards mercury with a detection limit of 1nM with least
      interference from most of the ions. The analytical utility of the proposed
      electrode has been validated by determining the mercury levels in number of
      sample matrices. 

PMID- 24881535
TI  - Design, fabrication and evaluation of intelligent sulfone-selective
      polybenzimidazole nanofibers.
AB  - Molecularly imprinted polybenzimidazole nanofibers fabricated for the adsorption
      of oxidized organosulfur compounds are presented. The imprinted polymers
      exhibited better selectivity for their target model sulfone-containing compounds
      with adsorption capacities of 28.5+/-0.4mg g(-1), 29.8+/-2.2mg g(-1) and 20.1+/
      1.4mg g(-1) observed for benzothiophene sulfone (BTO2), dibenzothiophene sulfone
      (DBTO2) and 4,6-dimethyldibenzothiophene sulfone (4,6-DMDBTO2) respectively.
      Molecular modeling based upon the density functional theory (DFT) indicated that
      hydrogen bond interactions may take place between sulfone oxygen groups with NH
      groups of the PBI. Further DFT also confirmed the feasibility of pi-pi
      interactions between the benzimidazole rings and the aromatic sulfone compounds.
      The adsorption mode followed the Freundlich (multi-layered) adsorption isotherm
      which indicated possible sulfone-sulfone interactions. A home-made pressurized
      hot water extraction (PHWE) system was employed for the extraction/desorption of
      sulfone compounds within imprinted nanofibers at 1mL min(-1), 150 degrees C and
      30 bar. PHWE used a green solvent (water) and achieved better extraction yields
      compared to the Soxhlet extraction process. The application of molecularly
      imprinted polybenzimidazole (PBI) nanofibers displayed excellent sulfur removal,
      with sulfur in fuel after adsorption falling below the determined limit of
      detection (LOD), which is 2.4mg L(-1)S, and with a sulfur adsorption capacity of
      5.3+/-0.4mg g(-1) observed for application in the fuel matrix.

PMID- 24881536
TI  - Extraction of pyridine derivatives from human urine using electromembrane
      extraction coupled to dispersive liquid-liquid microextraction followed by gas
      chromatography determination.
AB  - In the present work, some of pyridine derivatives were analyzed for the first
      time in complicated biological fluids by coupling electromembrane extraction with
      dispersive liquid-liquid microextraction (EME-DLLME). 3-Methylpyridine, 2,4
      lutidine, quinoline and 4-dimethylaminopyridine (DMAP) were extracted from urine
      and water samples. Effective parameters on the efficiencies of EME and DLLME were
      optimized by one variable at a time method and face-centered central composite
      design (FCCCD), respectively. The supported liquid phase (SLM) employed for the
      extraction of the analytes was a mixture of 90% 2-nitrophenyl octyl ether (NPOE)
      and 10% di-(2-ethylhexyl) phosphate (DEHP) which was immobilized in the pores of
      a piece of hollow fiber. An electric field was applied to carry over the analytes
      into acceptor solution. The acceptor solution was transferred to 1mL of an
      alkaline solution (pH=13) and then DLLME procedure was performed.
      Preconcentration factors in the range of 40-263 and satisfactory repeatabilities
      (2.3<RSD%<5.3) were obtained in different matrices. The method offered a good
      linearity with coefficient of determination greater than 0.9948 and was utilized
      for determination and quantification of pyridine compounds in smokers' urine
      samples. The proposed technique can be introduced as a simple, fast and
      inexpensive method for diagnosis of smokers.

PMID- 24881537
TI  - A thermostated electrochemical flow cell with a coupled bismuth film electrode
      for square-wave anodic stripping voltammetric determination of cadmium(II) and
      lead(II) in natural, wastewater and tap water samples.
AB  - In order to reduce the sample consumption and waste generation for
      electrochemical purposes, a screen-printed electrode (SPE) used for
      electrodeposition of bismuth film (SPE-BiFE) and a thermostated electrochemical
      flow cell (EFC) were developed. The SPE-BiFE with the EFC was employed to
      determine Cd(2+) and Pb(2+) ions in natural, wastewater and tap water samples by
      square-wave anodic stripping voltammetry (SWASV). For this, the flow-batch
      analysis (FBA) approach based on solenoid micro-pumps and three-way valves was
      developed to carry out a fully automated procedure with temperature control.
      Furthermore, the FBA and the SWASV parameters were optimized, on line
      simultaneous determination of Cd(2+) and Pb(2+) ions was performed and two
      analytical curves were linearly acquired in the concentration ranges from 6.30 to
      75.6ug L(-1) and from 3.20 to 38.4ug L(-1), respectively. Moreover, limits of
      detection of 0.60ug L(-1) and 0.10ug L(-1) for Cd(2+) and Pb(2+), respectively,
      were obtained. Studies of precision for the same SPE-BiFE and repeatability for
      five built SPE-BiFE were carried out for Cd(2+) and Pb(2+) ion measurements and
      RSD of 4.1% and 2.9% (n=3) with repeatabilities (n=5) of 6.5% and 8.0% were
      respectively obtained for both analytes. Besides, a low consumption of 700uL of
      reagents and a sampling frequency of 13h(-1) were acquired. Simplicity, fast
      response, accuracy, high portability, robustness and suitability for in loco
      analyses are the main features of the proposed electroanalytical method.

PMID- 24881538
TI  - Mass spectrometry-based tag and its application to high efficient peptide
      analysis - A review.
AB  - Chemical derivatization is a very promising technique for improving analysis of
      peptides by mass spectrometry (MS). Thereinto, development of novel tags
      compatible with MS and/or MS/MS has always been the focus point of study. In this
      review, the recent reported tags for derivatization of thiol groups of cysteine,
      carboxyl groups, and amino groups on peptides as well as peptides with post
      translational modifications (PTMs) are summarized. Moreover, the tags used for
      derivatization of glycans or oligosaccharides released from glycoproteins are
      also reviewed. 

PMID- 24881539
TI  - Use of UV-vis-NIR spectroscopy to monitor label-free interaction between
      molecular recognition elements and erythropoietin on a gold-coated polycarbonate
      platform.
AB  - Label-free-based detection is pivotal for real-time monitoring of biomolecular
      interactions and to eliminate the need for labeling with tags that can occupy
      important binding sites of biomolecules. One simplest form of label-free-based
      detection is ultraviolet-visible-near-infrared (UV-vis-NIR) spectroscopy, which
      measure changes in reflectivity as a means to monitor immobilization and
      interaction of biomolecules with their corresponding partners. In biosensor
      development, the platform used for the biomolecular interaction should be
      suitable for different molecular recognition elements. In this study, gold (Au)
      coated polycarbonate was used as a platform and as a proof-of-concept,
      erythropoietin (EPO), a doping substance widely abused by the athletes was used
      as the target. The interaction of EPO with its corresponding molecular
      recognition elements (anti-EPO monoclonal antibody and anti-EPO DNA aptamer) is
      monitored by UV-vis-NIR spectroscopy. Prior to this, to show that UV-vis-NIR
      spectroscopy is a suitable method for measuring biomolecular interaction, the
      interaction between biotin and streptavidin was demonstrated via this strategy
      and reflectivity of this interaction decreased by 25%. Subsequent to this,
      interaction of the EPO with anti-EPO monoclonal antibody and anti-EPO DNA aptamer
      resulted in the decrease of reflectivity by 5% and 10%, respectively. The results
      indicated that Au-coated polycarbonate could be an ideal biosensor platform for
      monitoring biomolecular interactions using UV-vis-NIR spectroscopy. A smaller
      version of the Au-coated polycarbonate substrates can be derived from the recent
      set-up, to be applied towards detecting EPO abuse among atheletes. 

PMID- 24881540
TI  - 3D-printed and CNC milled flow-cells for chemiluminescence detection.
AB  - Herein we explore modern fabrication techniques for the development of
      chemiluminescence detection flow-cells with features not attainable using the
      traditional coiled tubing approach. This includes the first 3D-printed
      chemiluminescence flow-cells, and a milled flow-cell designed to split the
      analyte stream into two separate detection zones within the same polymer chip.
      The flow-cells are compared to conventional detection systems using flow
      injection analysis (FIA) and high performance liquid chromatography (HPLC), with
      the fast chemiluminescence reactions of an acidic potassium permanganate reagent
      with morphine and a series of adrenergic phenolic amines. 

PMID- 24881541
TI  - Molecular interaction study of flavonoid derivative 3d with human serum albumin
      using multispectroscopic and molecular modeling approach.
AB  - Human serum albumin (HSA) has been developed as a model protein to study drug
      protein interaction. In the present work, the interaction between our synthesized
      flavonoid derivative 3d (possessing potent antitumor activity against HepG2
      cells) and HSA was investigated using fluorescence spectroscopy, circular
      dichroism spectroscopy, UV-vis spectroscopy and molecular modeling approach.
      Fluorescence spectroscopy showed that the fluorescence of HSA can be quenched
      remarkably by 3d under physiological condition with a slight shift of maximum
      fluorescence emission bands from 360nm to 363nm. Calculated results from Stern
      Volmer equation and modified Stern-Volmer equation indicated that the
      fluorescence was quenched by static quenching processing with association
      constant 5.26+/-0.04*10(4)L mol(-1) at 298K. After comprehensive consideration of
      the free energy change DeltaG, enthalpy change DeltaH and entropy change DeltaS,
      electrostatic interactions were confirmed as the main factor that participate in
      stabilizing the 3d-HSA complex. Both dichroism spectroscopy and UV-vis
      spectroscopy indicated conformational change of HSA after binding to 3d.
      Moreover, the structure of HSA was loosened and the percentage of alpha-helix
      decreased with increasing concentration of 3d. Molecular modeling results
      demonstrated that 3d could bind to HSA well into subdomain IIA, which is related
      to its capability of deposition and delivery. Three cation-pi interactions and
      three hydrogen bonds occurred between 3d and amino acid residuals ARG218, ARG222
      and LYS199. In conclusion, flavonoid derivative 3d can bind to HSA with
      noncovalent bond in a relatively stable way, so it can be delivered by HSA in a
      circulatory system.

PMID- 24881543
TI  - An aptamer-based quartz crystal microbalance biosensor for sensitive and
      selective detection of leukemia cells using silver-enhanced gold nanoparticle
      label.
AB  - An aptamer-based quartz crystal microbalance (QCM) biosensor was developed for
      the selective and sensitive detection of leukemia cells. In this strategy,
      aminophenylboronic acid-modified gold nanoparticles (APBA-AuNPs) which could bind
      to cell membrane were used for the labeling of cells followed by silver
      enhancement, through which significant signal amplification was achieved. Both
      the QCM and fluorescence microscopy results manifested the selectivity of the
      sensor designed. A good linear relationship between the frequency response and
      cell concentration over the range of 2*10(3)-1*10(5)cells/mL was obtained, with a
      detection limit of 1160cells/mL. This approach provides a simple, rapid, and
      economical method for leukemia cell analysis which might have great potential for
      further use. 

PMID- 24881542
TI  - Assessing crop residue phosphorus speciation using chemical fractionation and
      solution 31P nuclear magnetic resonance spectroscopy.
AB  - At physiological maturity, nutrients in crop residues can be released to the soil
      where they are incorporated into different labile and non-labile pools while the
      remainder is retained within the residue itself. The chemical speciation of
      phosphorus (P) in crop residues is an important determinant of the fate of this
      P. In this study, we used chemical fractionation and (31)P nuclear magnetic
      resonance (NMR) spectroscopy, first separately and then together, to evaluate the
      P speciation of mature oat (Avena sativa) residue. Two water extracts (one
      employing shaking and the other sonication) and two acid extracts (0.2N
      perchloric acid and 10% trichloroacetic acid) of these residues contained similar
      concentrations of orthophosphate (molybdate-reactive P determined by colorimetry)
      as NaOH-EDTA extracts of whole plant material subsequently analysed by solution
      (31)P NMR spectroscopy. However, solution (31)P NMR analysis of the extracts and
      residues isolated during the water/acid extractions indicated that this
      similarity resulted from a fortuitous coincidence as the orthophosphate
      concentration in the water/acid extracts was increased by the hydrolysis of
      pyrophosphate and organic P forms while at the same time there was incomplete
      extraction of orthophosphate. Confirmation of this was the absence of
      pyrophosphate in both water and acid fractions (it was detected in the whole
      plant material) and the finding that speciation of organic P in the fractions
      differed from that in the whole plant material. Evidence for incomplete
      extraction of orthophosphate was the finding that most of the residual P in the
      crop residues following water/acid extractions was detected as orthophosphate
      using (31)P NMR. Two methods for isolating and quantifying phospholipid P were
      also tested, based on solubility in ethanol:ether and ethanol:ether:chloroform.
      While these methods were selective and appeared to extract only phospholipid P,
      they did not extract all phospholipid P, as some was detected by NMR in the crop
      residue after extraction. These results highlight the need for careful
      interpretation of results from chemical fractionation, as separation can be
      compromised by incomplete recovery and side reactions. This study also highlights
      the benefits of employing a technique that can simultaneously detect multiple P
      species (solution (31)P NMR) in combination with chemical fractionation. 

PMID- 24881546
TI  - Determination of boiling point of petrochemicals by gas chromatography-mass
      spectrometry and multivariate regression analysis of structural activity
      relationship.
AB  - Accurate understanding of analyte boiling points (BP) is of critical importance
      in gas chromatographic (GC) separation and crude oil refinery operation in
      petrochemical industries. This study reported the first combined use of GC
      separation and partial-least-square (PLS1) multivariate regression analysis of
      petrochemical structural activity relationship (SAR) for accurate BP
      determination of two commercially available (D3710 and MA VHP) calibration gas
      mix samples. The results of the BP determination using PLS1 multivariate
      regression were further compared with the results of traditional simulated
      distillation method of BP determination. The developed PLS1 regression was able
      to correctly predict analytes BP in D3710 and MA VHP calibration gas mix samples,
      with a root-mean-square-%-relative-error (RMS%RE) of 6.4%, and 10.8%
      respectively. In contrast, the overall RMS%RE of 32.9% and 40.4%, respectively
      obtained for BP determination in D3710 and MA VHP using a traditional simulated
      distillation method were approximately four times larger than the corresponding
      RMS%RE of BP prediction using MRA, demonstrating the better predictive ability of
      MRA. The reported method is rapid, robust, and promising, and can be potentially
      used routinely for fast analysis, pattern recognition, and analyte BP
      determination in petrochemical industries. 

PMID- 24881545
TI  - A colorimetric microwell method using a desktop scanner for biochemical assays.
AB  - A method for rapid, inexpensive and sensitive simultaneous analysis of glucose,
      creatinine, triglycerides, total cholesterol and total protein is needed to
      analyze blood. The proposed method is based on the production of a specific color
      after reaction. The method was adapted to a 64-microwell plate format, and it
      uses the transparency scanner feature of a commercially available desktop
      scanner. Each microwell plate had an 8*8 array of flat-bottomed 250MUL
      microwells, and these microwells were used to simultaneously house the solutions
      for clinical assay. The scanned image was saved in TIFF format in a portable
      computer and then processed using a Graphic User Interface (GUI) designed in our
      laboratory to obtain analytical curves and to automate the mathematics and
      statistics calculations. This automation improved the analytical frequency of the
      method. The results showed that it is possible to measure a few microliters of
      solution with exactitude and precision better than 5.30%. The measured
      concentration ranges of glucose, triglycerides, creatinine, total cholesterol and
      total protein were 0.781 to 100, 1.56 to 200, 0.031 to 4.0, 1.56 to 200mg dL(-1)
      and 0.031 to 4.0g dL(-1), respectively. The limits of detection were 16.2, 51.7,
      0.12, 41.5mg dL(-1) and 0.62g dL(-1) for glucose, triglycerides, creatinine,
      total cholesterol and total protein, respectively. The recoveries were from 98.7%
      to 101.3% for total cholesterol, 98.7% to 124.9% for triglycerides, 54.2% to
      98.3% for total protein, 89.6% to 101% for glucose and 65.7% to 115.4% for
      creatinine. The results provided by the scanner were compared with those obtained
      with a commercial photometer and did not show significant differences at a
      confidence level of 95%. Good results were obtained for the correlation
      coefficient and Root Mean Square Error of Prediction (RMSEP) values for the five
      parameters, especially the total cholesterol and creatinine. The RMSEP values for
      glucose, creatinine, triglyceride, total cholesterol and total protein were 8.05,
      0.28, 7.69, 1.41mg dL(-1) and 2.2g dL(-1), respectively.

PMID- 24881544
TI  - The effects of lipids and surfactants on TLR5-proteoliposome functionality for
      flagellin detection using surface plasmon resonance biosensing.
AB  - The use of proteoliposomes as affinity elements in conjunction with a surface
      plasmon resonance sensor is a high-sensitivity alternative for the detection of
      multiple analytes. However, one of the most important aspects of these
      conformations is maintaining the functionality of the immobilized protein, which
      is determined by the choice of lipids and surfactants employed in the
      reconstitutions. Previously, we demonstrated the functionality of TLR5
      proteoliposomes as screening affinity elements of bacterial flagellin. In this
      new study we change the conditions of immobilization of TLR5 and evaluate how the
      fluidity of the membrane and the final size of the liposomes affect the
      functionality of the construct and thus increase their utility as an affinity
      element for design of new biosensors. In particular, we used reconstructions into
      preformed liposomes composed of the lipids POPC, POPC-DMPC and POPC-POPE mediated
      by the use of surfactants OG, Triton X100, and DDM, respectively. The affinity
      results were evaluated by SPR technology proteoliposomes and were correlated with
      the anisotropic change in the membrane status; the final sizes of the
      proteoliposomes were estimated. Our results clearly show the dependence of
      fluidity and final size of the proteoliposomes with surface plasmon resonance
      affinity measurements. 

PMID- 24881548
TI  - Determination of total thyroxine in human serum by hollow fiber liquid-phase
      microextraction and liquid chromatography-tandem mass spectrometry.
AB  - Determination of total thyroxine in human serum using hollow fiber liquid-phase
      microextraction (HF-LPME) has been accomplished for the first time. HF-LPME
      serves as an inexpensive sample pretreatment and the cleanup method that is
      nearly solvent-free. Thyroxine was extracted through a water immiscible organic
      solvent immobilized in the wall pores of a polypropylene hollow fiber into 20MUl
      of an aqueous acceptor phase inside the lumen of the hollow fiber. This technique
      produced extracts that had comparable cleanness with those obtained using solid
      phase extraction (SPE). Serum samples with endogenous thyroxine were spiked with
      isotopically-labeled thyroxine and analyzed by liquid chromatography-tandem mass
      spectrometry after HF-LPME extraction. Extraction parameters including the
      organic phase, acid/base concentration of acceptor phase, stirring speed and
      extraction time were optimized. The calibration range was found to be linear over
      1-1000ng/g with the limit of detection (LOD) of 0.3 ng/g. For quantification of
      total thyroxine in human serum, 6 subsamples were prepared and the results
      indicated very good precision with a relative standard deviation of <1.3%. The
      difference from the SPE method was less than 1.2%, with independent t-test
      showing insignificant bias. Two reference materials of human serum were analyzed,
      and our obtained values were compared with the reference values. The results
      showed very good precision with RSD around 0.2% and the deviation from the
      reference values were -3.1% and -2.1%. The newly developed method is precise,
      accurate, inexpensive, and environmentally friendly. 

PMID- 24881547
TI  - Evaluation of a molecularly imprinted polymer for determination of steroids in
      goat milk by matrix solid phase dispersion.
AB  - A molecularly imprinted polymer-matrix solid-phase dispersion methodology for
      simultaneous determination of five steroids in goat milk samples was proposed.
      Factors affecting the extraction recovery such as sample/dispersant ratio and
      washing and elution solvents were investigated. The molecularly imprinted polymer
      used as dispersant in the matrix solid-phase dispersion procedure showed high
      affinity to steroids, and the obtained extracts were sufficiently cleaned to be
      directly analyzed. Analytical separation was performed by micellar electrokinetic
      chromatography using a capillary electrophoresis system equipped with a diode
      array detector. A background electrolyte composed of borate buffer (25mM, pH
      9.3), sodium dodecyl sulfate (10mM) and acetonitrile (20%) was used. The
      developed MIP-MSPD methodology was applied for direct determination of
      testosterone (T), estrone (E1), 17beta-estradiol (17beta-E2), 17alpha
      ethinylestradiol (EE2) and progesterone (P) in different goat milk samples. Mean
      recoveries obtained ranged from 81% to 110%, with relative standard deviations
      (RSD)<=12%. The molecularly imprinted polymer-matrix solid-phase dispersion
      method is fast, selective, cost-effective and environment-friendly compared with
      other pretreatment methods used for extraction of steroids in milk. 

PMID- 24881549
TI  - Stable isotopic internal standard correction for quantitative analysis of
      hydroxyeicosatetraenoic acids (HETEs) in serum by on-line SPE-LC-MS/MS in
      selected reaction monitoring mode.
AB  - The influence of the inclusion of a stable isotopic labeled internal standard
      (SIL-IS) on the quantitative analysis of hydroxyeicosatetranoic acids (HETEs) in
      human serum is evaluated in this research. A solid-phase extraction-liquid
      chromatography-tandem mass spectrometry (SPE-LC-MS/MS) platform, one of the
      preferred approaches for targeted analysis of biofluids through the selected
      reaction monitoring (SRM) operational mode, was used to determine HETEs. These
      compounds were chosen as targeted metabolites because of their involvement in
      cardiovascular disease, cancer and osteoporosis. 15HETE-d8 was chosen as internal
      standard to evaluate matrix effects. Thus, the physico-chemical properties of the
      SIL-IS were the basis to evaluate the analytical features of the method for each
      metabolite through four calibration models. Two of the models were built with
      standard solutions at different concentration levels, but one of the calibration
      sets was spiked with an internal standard (IS). The other two models were built
      with the serum pool from osteoporotic patients, which was spiked at different
      concentrations with the target analytes. In this case, one of the serum
      calibration sets was also spiked with the IS. The study shows that the IS allowed
      noticeable correction of matrix effects for some HETE isomers at certain
      concentration levels, while accuracy was decreased at low concentration (15ng/mL)
      of them. Therefore, characterization of the method has been properly completed at
      different concentration levels. 

PMID- 24881550
TI  - Novel imidazolium-embedded and imidazolium-spaced octadecyl stationary phases for
      reversed phase liquid chromatography.
AB  - Two new stationary phases modified by alkylimidazoliums were prepared for the
      first time and characterized. One of the new phases was obtained via monomeric
      immobilization of octadecylimidazole to gamma-chloropropyltrimethoxysilane
      modified silica to form polar-embedded phase; the other one was prepared by co
      immobilization of two silane coupling agents (gamma-chloropropyltrichlorosilane
      and octadecyltrichlorosilane) to silica, followed by quaternization of
      methylimidazole to form polar-spaced phase. This study was intended to compare
      the retention characteristics of these two stationary phases using linear
      solvation energy relationships model, as well as to examine the difference in
      selectivity by eluting alkylbenzenes, alkylnaphthalenes, condensed-ring and
      phenylene polynuclear aromatic hydrocarbons on both phases. Different effects of
      distributions of polar functional group and octadecyl chain were found to impact
      the chromatographic properties. 

PMID- 24881551
TI  - Highly sensitive and selective fluorescence detection of copper (II) ion based on
      multi-ligand metal chelation.
AB  - A fluorescent probe was synthesized and demonstrated to be highly selective and
      sensitive in the reaction with copper (II) ion, generating a large variation of
      the fluorescence intensity in a dose-response manner. The probe contains a dansyl
      moiety as fluorophore and a multidentate ligand for copper (II) ion recognition.
      The reaction of the molecular probe with copper (II) ion proceeds rapidly and
      irreversibly in a 1 to 1 stoichiometric way, leading to the production of stable
      copper (II) complex, which subsequently results in the quenching of fluorescence.
      The detection limit for copper (II) ion was measured to be about 2ppb. It was
      also shown that the probe has high selectivity for copper (II) ion and good anti
      interference ability against other transition metal ions. The herein reported
      very simple and reliable fluorescence probe could be employed for copper (II) ion
      detection in many aspects. 

PMID- 24881552
TI  - Development a novel supramolecular solvent microextraction procedure for copper
      in environmental samples and its determination by microsampling flame atomic
      absorption spectrometry.
AB  - A supramolecular solvent (Ss) made up of reverse micelles of 1-decanol in
      tetrahydrofuran (THF): water was used for the fast and selective microextraction
      of Cu(II) prior to its determination by microsampling flame atomic absorption
      spectrometry (FAAS). Cu(II) was complexed with dimethyl dithiocarbamate (DMDC) to
      obtain hydrophobic complex and extracted to supramolecular solvent phase. The
      influences of some analytical parameters including pH, type and volume of
      supramolecular solvent, amount of complexing agent, ultrasonication and
      centrifuge time and sample volume were investigated. The effects of matrix
      components were also examined. The detection limit (LOD) and the quantification
      limit (LOQ) were 0.52ug L(-1) and 1.71ug L(-1) respectively. An preconcentration
      factor was obtained as 60 and the relative standard deviation was <3%. The
      accuracy of the developed method was evaluated by the analysis of the certified
      reference materials (TMDA-64.2 water, SRM 1568A Rice Flour and 8433 Corn Bran)
      and addition-recovery tests. The presented supramolecular solvent based liquid
      liquid microextraction (SsLLME) procedure was applied to the determination of
      copper in food and water samples with satisfactory results.

PMID- 24881553
TI  - Optical sensor for carbon dioxide gas determination, characterization and
      improvements.
AB  - A study of different alternatives to improve the stability and lifetime of
      sensors for the determination of gaseous CO2 has been performed. It includes the
      characterization of different sensing membranes, a discussion of the results
      obtained and possibilities for the future. The solid sensor membrane for gaseous
      CO2 based on changes in the luminiscence of a luminophore immobilized on O2
      insensitive film, concurrent with the displacement of a pH indicator, has some
      drawbacks, such as the loss of efficiency over time and the need to maintain the
      sensor in special atmospheric conditions. As a solution to these drawbacks, two
      alternatives were tested, the first alternative was replacing the newly proposed
      tetraoctyl ammonium hydroxide (TOAOH ) phase transfer agent with other basic
      agents that did not undergo a Hoffman degradation reaction, and the second
      alternative was the use of hydrophilic polymers that could retain water needed
      for CO2 sensing more efficiently. The different membranes tested indicated that
      the use of tetramethyl ammonium (TMAOH) instead of TOAOH as the phase transfer
      agent produced better results regarding stability and sensitivity. In addition,
      replacing the membrane polymer with hydrophilic polymers improved the sensing
      characteristics in terms of response time and stability over hydrophobic
      polymers. With a detection limit of 0.006%, the response time is 19s and the
      recovery time is 100s. The lifetime of the sensing membranes, which do not need
      to be held in any special atmosphere other than darkness, is longer than at least
      300 days for membranes with TMAOH in hydrophilic polymer and 515 days for
      membranes with TMAOH in ethyl cellulose. 

PMID- 24881554
TI  - Development of poly(3-aminophenylboronic acid) modified graphite rod electrode
      suitable for fluoride determination.
AB  - Poly(3-aminophenylboronic acid), (PAPBA) film was formed on the graphite rod
      surface by potential cycling. The PAPBA-modified graphite rod (PAPBA/GR)
      electrode prepared in this way was used for potentiometric fluoride
      determination. The linear calibration range was from 5*10(-4) to 5*10(-2)M with
      the slope of the linear part of the calibration curve of 42.5mV/logC. No
      interference effect of the most common ions such as sodium, potassium, chloride,
      nitrate, iodide, calcium, zinc, aluminum, sulfate and sorbitol was observed
      during electrochemical determination of fluoride. On the other hand, the PAPBA/GR
      electrode showed not only good sensitivity and selectivity, but also relatively
      rapid response to changes of analyte concentrations in the range of 20s. The
      sensor was successfully applied for fluoride determination in real sample -
      toothpaste. 

PMID- 24881555
TI  - Influence of carbon-based nanomaterials on lux-bioreporter Escherichia coli.
AB  - The cytotoxic effects of carbon-based nanomaterials are evaluated via the
      induction of luminescent genetically engineered Escherichia coli bacterial cells.
      Specifically, two engineered E. coli bacteria strains of DPD2794 and TV1061 were
      incubated with aqueous dispersion of three carbon allotropes (multi-wall carbon
      nanotubes (MWCNTs), graphene nanosheets and carbon black nanopowders) with
      different concentrations and the resulting bioluminescence was recorded at 30
      degrees C and 25 degrees C, respectively. The corresponding optical density
      changes of bacterial cells in the presence of various carbon nanomaterials were
      recorded as well. Based on these results, E. coli DPD2794 bacterial induction
      responds to a greater degree than E. coli TV1061 bacteria when exposed to various
      carbon-based nanomaterials. Finally, the surface morphology of E. coli DPD2794
      bacteria cells before and after carbon-based nanomaterials treatment was observed
      using a field emission scanning electron microscope (FESEM), from which
      morphological changes from the presence of carbon-based nanomaterials were
      observed and discussed. 

PMID- 24881556
TI  - The rm2 metrics and regression through origin approach: reliable and useful
      validation tools for predictive QSAR models (Commentary on 'Is regression through
      origin useful in external validation of QSAR models?').
AB  - Quantitative structure-activity relationship (QSAR) is an in silico technique
      which can be used in drug discovery, environmental fate modeling, property and
      toxicity prediction of chemical entities and regulatory toxicology. The
      predictive potential of a QSAR model is judged from various validation metrics in
      order to evaluate how well it is capable to predict endpoint values of new
      untested compounds. The rm2 group of metrics is one of the stringent validation
      metrics currently used by the QSAR fraternity in different reports. We
      scrutinized a recently published paper which raised an issue that the constructed
      criteria based on regression through origin (RTO) are not optimal and there is a
      significant difference in the rm2 metrics values computed from different
      statistical software packages. According to our point of view, the conclusion
      drawn in this paper appears to be misleading. Any inconsistency in the software
      algorithms has nothing to do with the calculation of rm2 metrics, as such
      computation is not limited by the use of any specific software, rather it depends
      only on fundamental mathematical formulae that are well established. However, it
      is a concern to the QSAR users that Excel and SPSS can return different results
      for the metrics using the RTO method. Thus, a proper validation of the software
      tool is required before its use for computation of any validation metric.

PMID- 24881558
TI  - Reply: tissue IgG4-positive plasma cells in inflammatory bowel disease: a study
      of 88 treatment-naive biopsies of inflammatory bowel disease.

PMID- 24881561
TI  - Prenatal exposure to integerrimine N-oxide impaired the maternal care and the
      physical and behavioral development of offspring rats.
AB  - Plants that contain pyrrolizidine alkaloids (PAs) have been reported as
      contaminants of pastures and food, as well as being used in herbal medicine. PAs
      are responsible for poisoning events in livestock and human beings. The aim of
      this present study was to evaluate effects of prenatal exposure to integerrimine
      N-oxide, the main PA found in the butanolic residue (BR) of Senecio brasiliensis,
      on both physical and behavioral parameters of Wistar rat offspring. The toxicity
      and maternal behavior were also evaluated. For this, pregnant Wistar rats
      received integerrimine N-oxide from the BR of Senecio brasiliensis, by gavage, on
      gestational days 6-20 (during organogenesis and fetal development period) at
      doses of 3, 6 and 9 mg/kg. During treatment, maternal body weight gain, and food
      and water intake were evaluated. After parturition, maternal behavior and
      aggressive maternal behavior were analyzed. In addition, physical development and
      behavioral assessments were observed in both male and female pups. Results showed
      that prenatal exposure to integerrimine N-oxide of S. brasiliensis induced
      maternal toxicity, impairment in maternal behavior and aggressive maternal
      behavior, mainly in the highest dose group. Between sexes comparison of pups
      showed loss of body weight, delayed physical development such as pinna
      detachment, hair growth, eruption of incisor teeth, eye and vaginal openings.
      These pups also showed a delay of palmar grasp, surface righting reflex, negative
      geotaxis and auditory startle reflexes. Thus, prenatal exposure to integerrimine
      N-oxide induces maternal toxicity, impairment of maternal care and delayed in
      physical and behavioral development of the offspring.

PMID- 24881562
TI  - Neocuproine-functionalized silica-coated magnetic nanoparticles for extraction of
      copper(II) from aqueous solution.
AB  - Neocuproine has been covalently bound to silica-coated maghemite (gamma-Fe2O3)
      magnetic nanoparticles (MNPs) by a phenyl ether linkage. The resulting MNPs are
      able to remove Cu(II) from 12 ppm aqueous solution with an extraction efficiency
      of up to 99% at pH 2.

PMID- 24881563
TI  - Hyperforin attenuates microglia activation and inhibits p65-Ser276 NFkappaB
      phosphorylation in the rat piriform cortex following status epilepticus.
AB  - Hyperforin, a lipophilic constituent of medicinal herb St. John's Wort, has
      neurobiological effects including antidepressant activity, antibiotic potency,
      anti-inflammatory activity and anti-tumoral properties. Furthermore, hyperforin
      activates transient receptor potential conical channel-6 (TRPC6), a nonselective
      cation channel. To elucidate the roles of hyperforin and TRPC6 in
      neuroinflammation in vivo, we investigated the effect of hyperforin on
      neuroinflammatory responses and its related events in the rat piriform cortex
      (PC) following status epilepticus (SE). Hyperforin attenuated microglial
      activation, p65-serine 276 NFkappaB phosphorylation, and suppressed TNF-alpha
      expression in the PC following SE. Hyperforin also effectively alleviated SE
      induced vasogenic edema formation, neuronal damage, microglial TRPC6 induction
      and blood-derived monocyte infiltration. Our findings suggest that hyperforin may
      effectively attenuate microglia-mediated neuroinflammation in the TRPC6
      independent manner. 

PMID- 24881564
TI  - Cultivated strains of Agaricus bisporus and A. brasiliensis: chemical
      characterization and evaluation of antioxidant and antimicrobial properties for
      the final healthy product--natural preservatives in yoghurt.
AB  - Agaricus bisporus (J. E. Lange) Emil J. Imbach and Agaricus brasiliensis Wasser,
      M. Didukh, Amazonas & Stamets are edible mushrooms. We chemically characterized
      these mushrooms for nutritional value, hydrophilic and lipophilic compounds. The
      antioxidant and antimicrobial activities of methanolic and ethanolic extracts
      were assessed. Hepatotoxicity was also evaluated. The ethanolic extract of both
      species was tested for inhibition of Listeria monocytogenes growth in yoghurt.
      Both species proved to be a good source of bioactive compounds. A. brasiliensis
      was richer in polyunsaturated fatty acids and revealed the highest concentration
      of phenolic acids, and tocopherols. A. bisporus showed the highest
      monounsaturated fatty acids and ergosterol contents. A. brasiliensis revealed the
      highest antioxidant potential, and its ethanolic extract displayed the highest
      antibacterial potential; the methanolic extract of A. bisporus revealed the
      highest antifungal activity. A. brasiliensis possessed better preserving
      properties in yoghurt. 

PMID- 24881565
TI  - Design, synthesis and evaluation of phenethylaminoheterocycles as K(v)1.5
      inhibitors.
AB  - Phenethylaminoheterocycles have been prepared and assayed for inhibition of the
      Kv1.5 potassium ion channel as a potential approach to the treatment of atrial
      fibrillation. A diverse set of heterocycles were identified as potent Kv1.5
      inhibitors and were advanced to pharmacodynamic evaluation based on selectivity
      and pharmacokinetic profile. Heterocycle optimization and template modification
      lead to the identification of compound 24 which demonstrated increased atrial
      effective refractory period in the rabbit pharmacodynamic model with mild effects
      on blood pressure and heart rate. 

PMID- 24881566
TI  - Identification of diarylsulfonamides as agonists of the free fatty acid receptor
      4 (FFA4/GPR120).
AB  - The exploration of a diarylsulfonamide series of free fatty acid receptor 4
      (FFA4/GPR120) agonists is described. This work led to the identification of
      selective FFA4 agonist 8 (GSK137647A) and selective FFA4 antagonist 39. The in
      vitro profile of compounds 8 and 39 is presented herein. 

PMID- 24881567
TI  - Towards the next generation of dual Bcl-2/Bcl-xL inhibitors.
AB  - Structural modifications of the left-hand side of compound 1 were identified
      which retained or improved potent binding to Bcl-2 and Bcl-xL in in vitro
      biochemical assays and had strong activity in an RS4;11 apoptotic cellular assay.
      For example, sulfoxide diastereomer 13 maintained good binding affinity and
      comparable cellular potency to 1 while improving aqueous solubility. The
      corresponding diastereomer (14) was significantly less potent in the cell, and
      docking studies suggest that this is due to a stereochemical preference for the
      RS versus SS sulfoxide. Appending a dimethylaminoethoxy side chain (27) adjacent
      to the benzylic position of the biphenyl moiety of 1 improved cellular activity
      by approximately three-fold, and this activity was corroborated in cell lines
      overexpressing Bcl-2 and Bcl-xL. 

PMID- 24881568
TI  - Recent developments in the discovery of FFA1 receptor agonists as novel oral
      treatment for type 2 diabetes mellitus.
AB  - Despite the availability of established medication for treatment of type 2
      diabetes mellitus (T2DM) there still remains a significant unmet need for new
      effective, oral antidiabetic agents that improve glycemic control while
      maintaining an excellent safety profile. In this regard the FFA1 receptor has
      emerged as an attractive target in recent years. Activation of the FFA1 receptor
      has been shown to not only amplify glucose induced insulin secretion from
      pancreatic beta cells but also to stimulate incretin secretion from intestinal
      endocrine cells. The current review highlights on the latest developments and
      clinical data from evolving research on the potential of FFA1 agonists as
      effective treatment for T2DM. 

PMID- 24881569
TI  - Modulation of human neutrophil activity by adenosine modified with a carborane
      pharmacophore.
AB  - An impact of adenosine modification with electroneutral, lipophilic 1,12-dicarba
      closo-dodecaborane or electronegative 7,8-dicarba-nido-undecaborane boron cluster
      at the 6-N, 2'-C and 2-C positions on human neutrophil oxidative burst,
      neutrophil adherence to fibronectin and protein kinase C activity was studied.
      Modification of adenosine with 1,12-dicarba-closo-dodecaborane, but not 7,8
      dicarba-nido-undecaborane, changes the function of adenosine from an inactive to
      an active state in regulating neutrophil response to PMA stimulation by reducing
      neutrophils' reactivity through a mechanism involving the PKC signaling pathway.
      Our results show that exogenously administered adenosine derivatives can be
      useful in regulating the oxidative burst of neutrophils in the inflammatory
      process. 

PMID- 24881570
TI  - Discovery of structurally simplified analogs of colchicine as an
      immunosuppressant.
AB  - We have discovered a new class of colchicine-derived therapeutic agents for
      immune diseases including rejection of organ-transplantation and autoimmune
      disease. Compound 2, which had been developed to overcome poor pharmacokinetic
      properties of compound 1, a first-generation colchicine analog, turned out to
      show toxicity such as intestinal toxicity and loss of weight during in vivo
      tests. The deletion of 7-carboxamide group and middle ring-truncation in
      colchicine allowed us to have structurally simplified analogs with strong
      immunosuppressive activity. Herein, we report non-alkaloid tricyclic compound 7
      and 12 as immunosuppressants which exhibited a strong immunosuppressive in vivo
      efficacy on the T-dependent antibody response, the Zymosan A-induced arthritis
      model and the Carrageenan-induced edema model. Compound 7 and 12 revealed less
      toxicity than the previous lead compound 2, and their minimum lethal doses (MLD)
      were proved to exceed 100 mg/kg.

PMID- 24881571
TI  - Demyelinating evidences in CMS rat model of depression: a DTI study at 7 T.
AB  - Depression is among the most debilitating diseases worldwide. Long-term exposure
      to stressors plays a major role in development of human depression. Chronic mild
      stress (CMS) seems to be a valid animal model for depression. Diffusion tensor
      imaging (DTI) is capable of inferring microstructural abnormalities of the white
      matter and has shown to serve as non-invasive marker of specific pathology. We
      developed a CMS rat model of depression and validated with behavioral
      experiments. We measured the diffusion indices (mean diffusivity (MD), fractional
      anisotropy (FA), axial (lambda?) and radial (lambda?) diffusivity) to investigate
      the changes in CMS rat brain during depression onset. Diffusion indices have
      shown to be useful to discriminate myelin damage from axon loss. DTI was
      performed in both control and CMS rats (n=10, in each group) and maps of FA, MD,
      lambda? and lambda? diffusivity values were generated using in-house built
      software. The diffusion indices were calculated by region of interest (ROI)
      analysis in different brain regions like the frontal cortex, hippocampus,
      hypothalamus, cingulum, thalamus, caudate putamen, corpus callosum, cerebral
      peduncle and sensory motor cortex. The results showed signs of demyelination,
      reflected by increased MD, decreased FA and increased lambda?. The results also
      suggest a possible role of edema or inflammation concerning the brain morphology
      in CMS rats. The overall finding using DTI suggests there might be a major role
      of loss of myelin sheath, which leads to disrupted connectivity between the
      limbic area and the prefrontal cortex during the onset of depression. Our
      findings indicate that interpretation of these indices may provide crucial
      information about the type and severity of mood disorders. 

PMID- 24881572
TI  - Resting network is composed of more than one neural pattern: an fMRI study.
AB  - In resting state, the dynamics of blood oxygen level-dependent signals recorded
      by functional magnetic resonance imaging (fMRI) showed reliable modular
      structures. To explore the network property, previous research used to construct
      an adjacency matrix by Pearson's correlation and prune it using stringent
      statistical threshold. However, traditional analyses may lose useful information
      at middle to moderate high correlation level. This resting fMRI study adopted
      full connection as a criterion to partition the adjacency matrix into composite
      sub-matrices (neural patterns) and investigated the associated community
      organization and network features. Modular consistency across subjects was
      assessed using scaled inclusivity index. Our results disclosed two neural
      patterns with reliable modular structures. Concordant with the results of
      traditional intervention, community detection analysis showed that neural pattern
      1, the sub-matrix at highest correlation level, was composed of sensory-motor,
      visual associative, default mode/midline, temporal limbic and basal ganglia
      structures. The neural pattern 2 was situated at middle to moderate high
      correlation level and comprised two larger modules, possibly associated with
      mental processing of outer world (such as visuo-associative, auditory and sensory
      motor networks) and inner homeostasis (such as default-mode, midline and limbic
      systems). Graph theoretical analyses further demonstrated that the network
      feature of neural pattern 1 was more local and segregate, whereas that of neural
      pattern 2 was more global and integrative. Our results suggest that future
      resting fMRI research may take the neural pattern at middle to moderate high
      correlation range into consideration, which has long been ignored in extant
      literature. The variation of neural pattern 2 could be relevant to individual
      characteristics of self-regulatory functions, and the disruption in its topology
      may underlie the pathology of several neuropsychiatric illnesses. 

PMID- 24881573
TI  - Plasticity of the motor system in multiple sclerosis.
AB  - Multiple sclerosis (MS) is a chronic neurological disease characterized by
      inflammation and degeneration within the CNS. Over the course of the disease,
      most MS patients successively accumulate inflammatory lesions, axonal damage, and
      a rather diffuse CNS pathology, along with an increasing degree of disability.
      Pharmacological treatment options which are currently approved for MS aim at
      limiting inflammation and decreasing the relapse rate, or at simply relieving
      symptoms. Established disease-modifying and immunosuppressive treatments are
      unable to prevent the accumulation of pathology in most patients over long-term.
      Therefore, therapies promoting the innate ability of the CNS to compensate for
      dysfunction resulting from brain injury might be highly beneficial in MS. As a
      precondition, however, development of such strategies requires well-grounded
      knowledge about the extent to which central plasticity is intact and accessible
      in MS patients, and whether it is functionally relevant at all. This review will
      focus on plasticity of the motor system in patients with MS. A number of
      functional imaging studies have assessed patterns of brain activation during
      simple motor tasks in MS patients and their relationship with CNS damage and
      motor function. Deeper insights about causal and functional relationships were
      gained by neurophysiological techniques, predominantly by transcranial magnetic
      stimulation. In addition, and probably closest to rehabilitative approaches,
      practice-induced plasticity has been probed in a few studies. Altogether, there
      is growing evidence for a preservation of rapid-onset motor plasticity and for
      functionally relevant chronic reorganization processes, which might be limited by
      high CNS injury in advanced stages of the disease. Clinical implications of these
      findings with regard to the development and optimization of rehabilitative
      treatments in MS are discussed, as well as open questions which need to be
      addressed by future studies. 

PMID- 24881574
TI  - Role of nicotinic acetylcholine receptors in regulating dopamine neuron activity.
AB  - Midbrain dopamine (DA) neurons play a central role in a wide range of behaviors,
      from attention and motivation to motor control and reinforcement. The release of
      DA is modulated by a number of factors, and its deregulation has been implicated
      in multiple psychiatric disorders, such as addiction. In particular, nicotinic
      acetylcholine receptors (nAChRs) are key modulators of DA cells. Nicotine, the
      main addictive component in tobacco, strongly interacts with these receptors in
      the midbrain DA systems, resulting in reinforcing effects that are at the core of
      tobacco addiction. nAChRs are virtually expressed on every cell of the DA system,
      both at pre-, post- and extra-synaptic locations. The complex issue of
      interpreting the role of the large portfolio of different nAChR subtypes
      expressed on ventral tegmental area (VTA) and substantia nigra pars compacta
      (SNc) neurons, and especially their role in defining functional DAergic
      subpopulations, is far from being solved. In this review we will try to provide
      the reader with an integrative view of the nicotinic modulation of DA neurons and
      its influence at the cellular, systemic and behavioral levels (exploratory
      behavior), as well as its implication in the reinforcing effects of nicotine. 

PMID- 24881575
TI  - Effect of docosahexaenoic acid on hippocampal neurons in high-glucose condition:
      involvement of PI3K/AKT/nuclear factor-kappaB-mediated inflammatory pathways.
AB  - Accumulating evidence suggested that hyperglycemia played a critical role in
      hippocampus dysfunction in patients with diabetes mellitus. However, the
      multifactorial pathogenesis of hyperglycemia-induced impairments of hippocampal
      neurons has not been fully elucidated. Docosahexaenoic acid (DHA) has been shown
      to enhance learning and memory and affect neural function in various experimental
      conditions. The present study investigated the effects of DHA on the lipid
      peroxidation, the level of inflammatory cytokines and neuron apoptosis in the
      hippocampal neurons in high-glucose condition. High-glucose administration
      increased the level of tumor necrosis factor alpha (TNF-alpha) and IL-6, induced
      oxidative stress and apoptosis of hippocampal neurons in vitro. DHA treatment
      reduced oxidative stress and TNF-alpha expression, protected the hippocampal
      neurons by increasing AKT phosphorylation and decreasing caspase-3 and caspase-9
      expression. These results suggested that high-glucose exposure induced injury of
      hippocampal neurons in vitro, and the principle mechanisms involved in the
      neuroprotective effect of DHA were its antioxidant and anti-apoptotic potential.
      DHA may thus be of use in preventing or treating neuron-degeneration resulting
      from hyperglycemia. 

PMID- 24881576
TI  - Central serotonergic neuron deficiency in a mouse model of Zellweger syndrome.
AB  - Zellweger syndrome (ZS) is a severe peroxisomal disorder caused by mutations in
      peroxisome biogenesis, or PEX, genes. A central hallmark of ZS is abnormal
      neuronal migration and neurodegeneration, which manifests as widespread
      neurological dysfunction. The molecular basis of ZS neuropathology is not well
      understood. Here we present findings using a mouse model of ZS neuropathology
      with conditional brain inactivation of the PEX13 gene. We demonstrate that PEX13
      brain mutants display changes that reflect an abnormal serotonergic system -
      decreased levels of tryptophan hydroxylase-2, the rate-limiting enzyme of
      serotonin (5-hydroxytryptamine, 5-HT) synthesis, dysmorphic 5-HT-positive
      neurons, abnormal distribution of 5-HT neurons, and dystrophic serotonergic
      axons. The raphe nuclei region of PEX13 brain mutants also display increased
      levels of apoptotic cells and reactive, inflammatory gliosis. Given the role of
      the serotonergic system in brain development and motor control, dysfunction of
      this system would account in part for the observed neurological changes of PEX13
      brain mutants. 

PMID- 24881578
TI  - Entry of aminoglycosides into renal tubular epithelial cells via endocytosis
      dependent and endocytosis-independent pathways.
AB  - Aminoglycoside antibiotics such as gentamicin and amikacin are well recognized as
      a clinically important antibiotic class because of their reliable efficacy and
      low cost. However, the clinical use of aminoglycosides is limited by their
      nephrotoxicity and ototoxicity. Nephrotoxicity is induced mainly due to high
      accumulation of the antibiotics in renal proximal tubular cells. Therefore, a lot
      of studies on characterization of the renal transport system for aminoglycosides
      so far reported involved various in-vivo and in-vitro techniques. Early studies
      revealed that aminoglycosides are taken up through adsorptive endocytosis in
      renal epithelial cells. Subsequently, it was found that megalin, a multiligand
      endocytic receptor abundantly expressed on the apical side of renal proximal
      tubular cells, can bind aminoglycosides and that megalin-mediated endocytosis
      plays a crucial role in renal accumulation of aminoglycosides. Therefore, megalin
      has been suggested to be a promising molecular target for the prevention of
      aminoglycoside-induced nephrotoxicity. On the other hand, recently, some reports
      have indicated that aminoglycosides are transported via a pathway that does not
      require endocytosis, such as non-selective cation channel-mediated entry, in
      cultured renal tubular cells as well as cochlear outer hair cells. In this
      commentary article, we review the cellular transport of aminoglycosides in renal
      epithelial cells, focusing on endocytosis-dependent and -independent pathways. 

PMID- 24881577
TI  - Selective stimulation of neurons in visual cortex enables segregation of slow and
      fast connections.
AB  - Organization of the central visual pathway is generally studied from a
      perspective of feedforward processes. However, there are horizontal connections
      and also strong feedback from extra striate to visual cortex. Here, we use visual
      stimuli designed to maximize relative differential involvements of these three
      main types of connections. The approach relies on differences between stimulation
      within the classical receptive field (CRF) and that of the surround region.
      Although previous studies have used similar approaches, they were limited
      primarily to spatial segregation of neural connections. Our experimental design
      provides clear segregation of fast and slow components of surround modulation. We
      assume these are mediated by feedback and horizontal connections, respectively,
      but other factors may be involved. Our results imply that both horizontal and
      feedback connections contribute to integration of visual information outside the
      CRF and provide suppressive or facilitative modulation. For a given cell,
      modulation may change in strength and sign from suppression to facilitation or
      the reverse depending on surround parameters. Sub-threshold input from the CRF
      surround increases local field potential (LFP) power in distinct frequency ranges
      which differ for suppression and facilitation. Horizontal connections have
      delayed CRF-surround modulation and are sensitive to position changes in the
      surround. Therefore, surround information beyond the CRF is initially processed
      by fast connections which we consider to be feedback, whereas spatially tuned
      mechanisms are relatively slow and presumably mediated by horizontal connections.
      Overall, results suggest that convergent fast (feedforward) inputs determine size
      and structure of the CRFs of recipient cells in visual cortex. And fast
      connections from extra striate regions (feedback) plus slow-tuned connections
      (horizontal) within visual cortex contribute to spatial influences of CRF
      surround activation. 

PMID- 24881579
TI  - Transcriptome and exoproteome analysis of utilization of plant-derived biomass by
      Myceliophthora thermophila.
AB  - Myceliophthora thermophila is a thermophilic fungus whose genome encodes a wide
      range of carbohydrate-active enzymes (CAZymes) involved in plant biomass
      degradation. Such enzymes have potential applications in turning different kinds
      of lignocellulosic feedstock into sugar precursors for biofuels and chemicals.
      The present study examined and compared the transcriptomes and exoproteomes of M.
      thermophila during cultivation on different types of complex biomass to gain
      insight into how its secreted enzymatic machinery varies with different sources
      of lignocellulose. In the transcriptome analysis three monocot (barley, oat,
      triticale) and three dicot (alfalfa, canola, flax) plants were used whereas in
      the proteome analysis additional substrates, i.e. wood and corn stover pulps,
      were included. A core set of 59 genes encoding CAZymes was up-regulated in
      response to both monocot and dicot straws, including nine polysaccharide
      monooxygenases and GH10, but not GH11, xylanases. Genes encoding additional
      xylanolytic enzymes were up-regulated during growth on monocot straws, while
      genes encoding additional pectinolytic enzymes were up-regulated in response to
      dicot biomass. Exoproteome analysis was generally consistent with the conclusions
      drawn from transcriptome analysis, but additional CAZymes that accumulated to
      high levels were identified. Despite the wide variety of biomass sources tested
      some CAZy family members were not expressed under any condition. The results of
      this study provide a comprehensive view from both transcriptome and exoproteome
      levels, of how M. thermophila responds to a wide range of biomass sources using
      its genomic resources. 

PMID- 24881581
TI  - A specific fluorescent probe for NO based on a new NO-binding group.
AB  - By incorporation of a specific NO-binding group, 2-amino-3'
      dimethylaminobiphenyl, into a Bodipy dye, fluorescent probe was constructed,
      which exhibited high selectivity for NO over other ROS/RNS as well as DHA, AA and
      MGO. 

PMID- 24881582
TI  - Intracellular antibody capture: A molecular biology approach to inhibitors of
      protein-protein interactions.
AB  - Many proteins of interest in basic biology, translational research studies and
      for clinical targeting in diseases reside inside the cell and function by
      interacting with other macromolecules. Protein complexes control basic processes
      such as development and cell division but also abnormal cell growth when
      mutations occur such as found in cancer. Interfering with protein-protein
      interactions is an important aspiration in both basic and disease biology but
      small molecule inhibitors have been difficult and expensive to isolate. Recently,
      we have adapted molecular biology techniques to develop a simple set of protocols
      for isolation of high affinity antibody fragments (in the form of single VH
      domains) that function within the reducing environment of higher organism cells
      and can bind to their target molecules. The method called Intracellular Antibody
      Capture (IAC) has been used to develop inhibitory anti-RAS and anti-LMO2 single
      domains that have been used for target validation of these antigens in pre
      clinical cancer models and illustrate the efficacy of the IAC approach to
      generation of drug surrogates. Future use of inhibitory VH antibody fragments as
      drugs in their own right (we term these macrodrugs to distinguish them from small
      molecule drugs) requires their delivery to target cells in vivo but they can also
      be templates for small molecule drug development that emulate the binding sites
      of the antibody fragments. This article is part of a Special Issue entitled:
      Recent advances in molecular engineering of antibody.

PMID- 24881583
TI  - Severity of periodontitis in patients with isolated coronary artery ectasia.
AB  - The concept that coronary artery ectasia (CAE) is an inflammatory-related disease
      has been increasingly recognized. Periodontitis induced low-grade chronic
      systemic inflammation has been shown to be associated with cardiovascular
      diseases. The aim of the present study was to evaluate the association between
      periodontitis and CAE.Thirty-two patients with isolated CAE, and 28 age, sex and
      smoking status-matched subjects with normal coronary arteries (NCA) underwent
      full dental examinations. Periodontal disease was evaluated using the following
      clinical parameters; number of remaining teeth, plaque index (PI), gingival index
      (GI), bleeding on probing (BOP), and pocket depth (PD).Cases and controls did not
      differ according to their baseline characteristics and prevalence of traditional
      cardiovascular risk factors. Patients with isolated CAE had higher periodontal
      indices when compared to subjects with NCA (PD: 3.6 +/- 1.26 mm versus 2.3 +/-
      0.79 mm; GI: 2.29 +/- 0.86 versus 1.43 +/- 1.19; BOP (%): 52.18 +/- 20.1 versus
      27.8 +/- 10.9, P < 0.001, P < 0.05 and P < 0.05, respectively). Moreover, in
      multivariate analysis higher values for PD were found to be significant
      predictors for the likelihood of having coronary ectasia.The results of the
      present study demonstrate for the first time that there is an association between
      periodontitis and isolated CAE. 

PMID- 24881585
TI  - A case of thrombosis of intra-atrial extracardiac conduit and left pulmonary
      artery due to infective endocarditis after modified Fontan operation.
AB  - Previous studies have reported that the extracardiac Fontan procedure has
      excellent outcomes and a lower incidence of postoperative complications than the
      lateral tunnel procedure. However, thromboembolic events that occur after the
      Fontan procedure are a well-known cause of morbidity. We experienced a case of
      thrombosis of intra-atrial extracardiac conduit and the left pulmonary artery 2
      years after a modified Fontan operation due to infective endocarditis (IE)
      despite prophylactic antiplatelet therapy. The patient underwent reoperation. The
      conduit in the right atrium (RA) was excised, and the thrombus in the vessels was
      removed. Because the fibrous tissue in the RA around the conduit was firm, the
      tissue was used as the "tunnel" for the Fontan route between the IVC and the
      ePTFE graft outside the RA instead of replacement using another alien graft. He
      was discharged on postoperative day 45 and was medicated with coumadin and
      aspirin. He is now being followed in our outpatient clinic and is still without
      any sign of infection. 

PMID- 24881580
TI  - The proteome and phosphoproteome of Neurospora crassa in response to cellulose,
      sucrose and carbon starvation.
AB  - Improving cellulolytic enzyme production by plant biomass degrading fungi holds
      great potential in reducing costs associated with production of next-generation
      biofuels generated from lignocellulose. How fungi sense cellulosic materials and
      respond by secreting enzymes has mainly been examined by assessing function of
      transcriptional regulators and via transcriptional profiling. Here, we obtained
      global proteomic and phosphoproteomic profiles of the plant biomass degrading
      filamentous fungus Neurospora crassa grown on different carbon sources, i.e.
      sucrose, no carbon, and cellulose, by performing isobaric tags for relative and
      absolute quantification (iTRAQ)-based LC-MS/MS analyses. A comparison between
      proteomes and transcriptomes under identical carbon conditions suggests that
      extensive post-transcriptional regulation occurs in N. crassa in response to
      exposure to cellulosic material. Several hundred amino acid residues with
      differential phosphorylation levels on crystalline cellulose (Avicel) or carbon
      free medium vs sucrose medium were identified, including phosphorylation sites in
      a major transcriptional activator for cellulase genes, CLR1, as well as a
      cellobionic acid transporter, CBT1. Mutation of phosphorylation sites on CLR1 did
      not have a major effect on transactivation of cellulase production, while
      mutation of phosphorylation sites in CBT1 increased its transporting capacity.
      Our data provides rich information at both the protein and phosphorylation levels
      of the early cellular responses to carbon starvation and cellulosic induction and
      aids in a greater understanding of the underlying post-transcriptional regulatory
      mechanisms in filamentous fungi. 

PMID- 24881586
TI  - Patterns of decrease in multidirectional myocardial deformations in patients with
      fluctuating left ventricular ejection fraction.
AB  - Few studies have examined the variations in longitudinal/circumferential/radial
      strain (LS/CS/RS) and strain rate (LSr/CSr/RSr) in individual hearts when the
      left ventricular ejection fraction (LVEF) has changed. We hypothesized the
      relationships of strain/strain rate and LVEF are not linear, but vary with
      multiple inflection points (IPs) in individual hearts.Twenty-five patients with
      fluctuating LVEF (DeltaLVEF > 10%) who had 2-D speckle tracking echocardiography
      available for analysis were enrolled. After models of best fit were obtained from
      the 'collective' plots to determine inflection points, the decrements of slopes
      above inflection points (IP) were compared with those below IPs in the
      'individual hearts' plots.In the 'collective' plots, both LS and LSr linearly
      decreased in proportion to LVEF when LVEF >= 40% but remained constant regardless
      of LVEF when LVEF < 40% (IPs when LVEF = 40%, P < 0.0001). The RS-LVEF
      relationship was sigmoid with two IPs when LVEF = 30% and 50% (P < 0.0001).
      However, in the 'individual hearts' plots, the decrements of slopes above and
      below IPs were not different for LS-LVEF and LSr-LVEF, and marginally different
      for RS-LVEF (P = 0.049, across IP when LVEF = 50%).Collectively, the relationship
      of LS/LSr/RS and LVEF seemed to be not linear, but inflective, however, we could
      not prove the inflective relationship in individual hearts with fluctuating LVEF.
      Further study with more patients is needed to prove our hypothesis. 

PMID- 24881584
TI  - Prognostic impact of chronic kidney disease and anemia at admission on in
      hospital outcomes after primary percutaneous coronary intervention for acute
      myocardial infarction.
AB  - Cardiorenal anemia syndrome has recently been receiving greater attention;
      however, data regarding the relationship between chronic kidney disease
      (CKD)/anemia on presentation and in-hospital outcome in patients with acute
      myocardial infarction (AMI) undergoing primary percutaneous coronary intervention
      (PCI) are still limited in Japan.A total of 1,447 primary PCI-treated AMI
      patients were classified into 4 groups according to the presence of CKD and/or
      anemia on hospital admission (with CKD/with anemia n = 222, with CKD/without
      anemia n = 299, without CKD/with anemia n = 151, without CKD/without anemia n =
      775). Angiographic acute results of primary PCI were similar among the 4 groups.
      The patients with CKD had a significantly higher in-hospital overall mortality
      rate than the patients without CKD, and in the presence or absence of CKD,
      patients with anemia tended to have a higher in-hospital mortality rate than the
      patients without anemia. According to a multivariate analysis, anemia on
      admission was found to be an independent predictor of in-hospital mortality,
      whereas admission CKD and admission eGFR were statistically not independent
      predictors. Moreover, the multivariable adjusted odds ratio of in-hospital death
      in AMI patients with CKD alone was 1.855 (95% CI 0.929-3.706), and that in AMI
      patients with CKD/with anemia was 3.384 (95% CI 1.697-6.748).These results
      suggest that among real-world, unselected Japanese AMI patients undergoing
      primary PCI, the combination of CKD and anemia on admission confers significant
      adverse effects on in-hospital mortality. 

PMID- 24881587
TI  - Adaptive servo-ventilation therapy improves long-term prognosis in heart failure
      patients with anemia and sleep-disordered breathing.
AB  - Sleep disordered breathing (SDB) and anemia influences the progression of chronic
      heart failure (CHF). Adaptive servo-ventilation (ASV) is an effective therapeutic
      device for treatment of CHF, however, the impacts of ASV on CHF patients with or
      without anemia remain unclear.A total of 139 patients with CHF and SDB were
      divided into two groups: those treated with ASV (n = 53) and without ASV (n =
      86). All patients were prospectively followed after discharge with the endpoints
      of cardiac death or progressive heart failure requiring rehospitalization. There
      were 65 patients (47%) with anemia among all subjects. The apnea hypopnea index
      was improved, and plasma BNP and high sensitive C-reactive protein levels were
      decreased in both groups with and without anemia by ASV therapy. The Kaplan-Meier
      survival curve demonstrated that the cardiac event-free rate in patients with ASV
      was significantly higher than in those without ASV in the anemia group (P =
      0.008). However, in the non-anemia group, the cardiac event-free rate was
      similarly high in patients both with and without ASV (P = 0.664). Multivariate
      Cox proportional hazard analysis demonstrated that ASV use was an independent
      predictor of cardiac events in the anemia group (P = 0.0308), but not in the non
      anemia group.ASV treatment for CHF and SDB has more favorable impacts in patients
      with anemia than in those without anemia. 

PMID- 24881588
TI  - Differential impact on acute kidney injury incidence between on- and off pump
      coronary artery bypass grafting in octogenarians.
AB  - INTRODUCTION: Acute kidney injury (AKI) following surgical myocardial
      revascularization is associated with high mortality and morbidity. The aim of
      this study was to evaluate the risk of acute kidney injury in a population of
      very old patients following different surgical techniques. PATIENTS AND METHODS:
      A retrospective study of 310 consecutive patients aged 78 to 93 years, mean
      80.5+/-2.2, who underwent surgery at one cardiac surgery centre. Based on the
      surgical technique used the patients were divided into: Group I. CABG (n=134) -
      surgical myocardial revascularization using extracorporeal circulation and
      arterial and venous grafts. Group II. OPCABG (n=55) - surgical revascularization
      without extracorporeal circulation but using arterial and venous grafts. Group
      III. NOTOUCH (n=121) - no handling with the ascending aorta was performed at all.
      RESULTS: A statistically insignificant renoprotective trend was found in patients
      who underwent surgery without extracorporeal circulation regardless of technique.
      Comparing groups II and III vs. group I, a significantly poorer renal functioning
      (median difference in creatinine was 10.0 (32.9) vs 17.5 (35.0), P=0.05) was
      shown for patients in group I. CONCLUSION: Surgical myocardial revascularization
      without extracorporeal circulation in very old patients is safe. The results of
      this study show a renoprotective trend.

PMID- 24881589
TI  - Allergic contact dermatitis and changes in the frequency of the causative
      allergens demonstrated with patch testing in 2008-2012.
AB  - BACKGROUND: The frequency of contact allergens is often regionally different and
      hence it regional identification is important for the prevention of allergic
      contact dermatitis (ACD). OBJECTIVES: The aim of the study was to determine the
      most common contact allergens in the etiology of ACD from 2008-2012 and evaluate
      their dynamics in comparison with similar studies in the Czech Republic and
      internationally carried out in previous years. METHODS: A total of 1941 patients
      with suspected ACD were examined using the patch tests from the European Standard
      Series. The data obtained were subjected to statistical analysis. RESULTS: The
      most common contact allergy was to nickel (15.4%), the second most frequent
      allergen was Balsam of Peru (11.6%). The top five allergens in the whole sample
      also included, in descending order, fragrance-mix I (7.1%), cobalt chloride
      (6.4%), and Kathon CG (4.0%). While the order of contact allergens causing
      sensitisation in women is consistent with the results of the whole sample, in men
      instead of cobalt and Kathon CG, epoxy resin and chromium appeared among the five
      most common allergens. CONCLUSIONS: In the Czech Republic, despite existing EU
      legislation, action to reduce the frequency of sensitization to nickel failed in
      contrast to other EU countries. In addition to nickel, consistent preventive
      measures should be focused mainly on sensitization to Balsam of Peru, cobalt,
      epoxy resins, chromium and aromatic substances and preservatives used in the
      cosmetic industry.

PMID- 24881590
TI  - Prognostic value of stress-only and stress-rest normal gated SPECT imaging:
      higher incidence of cardiac hard events in diabetic patients who underwent full
      stress-rest imaging.
AB  - BACKGROUND: The European procedural guidelines for cardiac gated SPECT imaging
      demonstrate considerable variability in recommended administered
      radiopharmaceutical activity and imaging protocols. This study compared stress
      only and stress-rest protocols to evaluate the safety of stress-only imaging, and
      to identify characteristics of patients who need full stress-rest imaging.
      METHODS: Patients referred for a chest pain were scheduled for stress-rest gated
      SPECT imaging. If the stress images were interpreted as normal according to the
      perfusion and left ventricular function, the examination of patients was finished
      and patients did not undergo the rest imaging. A total number of 1063 patients
      was included (mean age 61 +/- 11 years). These patients have been followed for
      hard cardiac events, i.e. cardiac deaths or nonfatal myocardial infarction.
      RESULTS: During a follow-up of 3.2 +/- 2.5 years, hard events occurred in 12
      patients with normal SPECT and 59 with abnormal SPECT had hard events (0.7 vs.
      3.6% /year, P < 0.001). Among the 536 patients with normal study, there was no
      significantly lower incidence of hard events in the subgroup of patients with
      stress-only imaging (0.6 vs. 0.8% /year, P = 0.641). Diabetes mellitus was an
      independent predictor of hard events in patients with normal SPECT (1.3 vs.
      0.5%/year, P < 0.001). We found a higher incidence of hard events in diabetic
      patients with normal study with the necessity of full stress-rest imaging in
      comparison with those with stress-only imaging (1.7 vs. 0.7% /year, P < 0.001).
      CONCLUSIONS: Our results support the good prognosis of normal stress-only study.
      Diabetes mellitus was an independent predictor of hard events in patients with
      normal SPECT. Diabetic patients with normal results who required additional rest
      imaging had significant adverse outcome.

PMID- 24881591
TI  - HIV-related stigma among an urban sample of persons living with HIV at risk for
      dropping out of HIV-oriented primary medical care.
AB  - HIV-related stigma is one of the greatest barriers to preventing and ending the
      HIV epidemic. The purpose of our study was to examine HIV-related stigma among
      urban adults voluntarily seeking HIV-oriented primary medical care and at risk
      for dropping out after enrolling. The baseline cross-sectional analysis of
      perceived HIV-related stigma upon enrolling in care examined the level of HIV
      related stigma and its sub-domains: personalized, disclosure, negative self
      image, and public attitudes. Our study also identified precursors of HIV-related
      stigma and associated outcomes. HIV-related stigma continues to be a significant
      problem for persons living with HIV; those perceiving higher levels of HIV
      related stigma reported a poorer quality of life, both physically and mentally.
      The relationship between HIV-related stigma and mental health was closely
      connected in our sample. 

PMID- 24881593
TI  - Mitochondria: the gateway for tamoxifen-induced liver injury.
AB  - Tamoxifen (TAM) is routinely used in the treatment of breast carcinoma. TAM
      induced liver injury remains a major concern, as TAM causes hepatic steatosis in
      a significant number of patients, which can progress toward steatohepatitis.
      Liver toxicity is generally believed to involve mitochondrial dysfunction and TAM
      exerts multiple deleterious effects on mitochondria, which may account for the
      hepatotoxicity observed in patients treated with TAM. Endoxifen (EDX), a key
      active metabolite of TAM that is being investigated as an alternative to TAM in
      breast cancer therapy, slightly affects mitochondria in comparison with TAM and
      this demonstration well correlates with the absence of alterations in the
      clinical parameters of individuals taking EDX. The steady-state plasma
      concentrations of TAM and its active metabolites EDX and 4-hydroxytamoxifen
      (OHTAM) in patients taking TAM are highly variable, reflecting genetic variants
      of CYP2D6 involved in TAM metabolism. Besides de genetic polymorphisms, the
      intake of drugs that influence the enzymatic activity of CYP2D6 compromises the
      therapeutic efficiency of TAM. The knowledge of the impact of the variability of
      TAM metabolism in the breast cancer treatment explains the discrepant outcomes
      observed in patients taking TAM, as well as the individual variability of
      idiosyncratic liver injury and other sides effects observed. Therefore, and
      contrarily to the clinical use of EDX, the need of therapeutic drug monitoring
      and a regular assessment of liver function biomarkers should be considered in
      patients under therapies with TAM. In this review we focus on the mitochondrial
      effects of TAM and its metabolites and on the role played by mitochondria in the
      initiating events leading to TAM-induced hepatotoxicity, as well as the clinical
      implications. 

PMID- 24881592
TI  - Hepatic toxicity of dronedarone in mice: role of mitochondrial beta-oxidation.
AB  - Dronedarone is an amiodarone-like antiarrhythmic drug associated with severe
      liver injury. Since dronedarone inhibits mitochondrial respiration and beta
      oxidation in vitro, mitochondrial toxicity may also explain dronedarone
      associated hepatotoxicity in vivo. We therefore studied hepatotoxicity of
      dronedarone (200mg/kg/day for 2 weeks or 400mg/kg/day for 1 week by intragastric
      gavage) in heterozygous juvenile visceral steatosis (jvs(+/-)) and wild-type
      mice. Jvs(+/-) mice have reduced carnitine stores and are sensitive for
      mitochondrial beta-oxidation inhibitors. Treatment with dronedarone 200mg/kg/day
      had no effect on body weight, serum transaminases and bilirubin, and hepatic
      mitochondrial function in both wild-type and jvs(+/-) mice. In contrast,
      dronedarone 400mg/kg/day was associated with a 10-15% drop in body weight, and a
      3-5-fold increase in transaminases and bilirubin in wild-type mice and, more
      accentuated, in jvs(+/-) mice. In vivo metabolism of intraperitoneal (14)C
      palmitate was impaired in wild-type, and, more accentuated, in jvs(+/-) mice
      treated with 400mg/kg/day dronedarone compared to vehicle-treated mice. Impaired
      beta-oxidation was also found in isolated mitochondria ex vivo. A likely
      explanation for these findings was a reduced activity of carnitine
      palmitoyltransferase 1a in liver mitochondria from dronedarone-treated mice. In
      contrast, dronedarone did not affect the activity of the respiratory chain ex
      vivo. We conclude that dronedarone inhibits mitochondrial beta-oxidation in and
      ex vivo, but not the respiratory chain. Jvs(+/-) mice are slightly more sensitive
      for the effect of dronedarone on mitochondrial beta-oxidation than wild-type
      mice. The results suggest that inhibition of mitochondrial beta-oxidation is an
      important mechanism of hepatotoxicity associated with dronedarone. 

PMID- 24881594
TI  - Prevention of organophosphate-induced chronic epilepsy by early benzodiazepine
      treatment.
AB  - Poisoning with organophosphates (OPs) may induce status epilepticus (SE), leading
      to severe brain damage. Our objectives were to investigate whether OP-induced SE
      leads to the emergence of spontaneous recurrent seizures (SRSs), the hallmark of
      chronic epilepsy, and if so, to assess the efficacy of benzodiazepine therapy
      following SE onset in preventing the epileptogenesis. We also explored early
      changes in hippocampal pyramidal cells excitability in this model. Adult rats
      were poisoned with the paraoxon (450MUg/kg) and immediately treated with atropine
      (3mg/kg) and obidoxime (20mg/kg) to reduce acute mortality due to peripheral
      acetylcholinesterase inhibition. Electrical brain activity was assessed for two
      weeks during weeks 4-6 after poisoning using telemetric electrocorticographic
      intracranial recordings. All OP-poisoned animals developed SE, which could be
      suppressed by midazolam. Most (88%) rats which were not treated with midazolam
      developed SRSs, indicating that they have become chronically epileptic.
      Application of midazolam 1min following SE onset had a significant
      antiepileptogenic effect (only 11% of the rats became epileptic; p=0.001 compared
      to non-midazolam-treated rats). Applying midazolam 30min after SE onset did not
      significantly prevent chronic epilepsy. The electrophysiological properties of
      CA1 pyramidal cells, assessed electrophysiologically in hippocampal slices, were
      not altered by OP-induced SE. Thus we show for the first time that a single
      episode of OP-induced SE in rats leads to the acquisition of chronic epilepsy,
      and that this epileptogenic outcome can be largely prevented by immediate, but
      not delayed, administration of midazolam. Extrapolating these results to humans
      would suggest that midazolam should be provided together with atropine and an
      oxime in the immediate pharmacological treatment of OP poisoning. 

PMID- 24881595
TI  - Changing face of glaucoma.

PMID- 24881598
TI  - Deep anterior lamellar keratoplasty with a manual spatula: anatomical and
      functional results.
AB  - OBJECTIVE: Evaluate the anatomical, refractive, and functional results of an
      innovative technique of deep anterior lamellar keratoplasty with a manual
      spatula. MATERIALS AND METHODS: We evaluated the results and examinations of 16
      eyes from 14 patients who underwent deep anterior lamellar keratoplasty using the
      technique described by Ferrara. Residual bed thickness after keratoplasty was
      evaluated postoperatively using Visante. The measurement was performed using a
      technique similar to that used to measure flap thickness after laser in situ
      keratomileusis refractive surgery. The measurements were performed at the center
      of the cornea in an area comprising the central 3-mm in the 45 degrees  and 135
      degrees  meridians. RESULTS: Best-corrected visual acuity was 0.34 +/- 0.18
      LogMar (0.09 to 0.60 LogMar), the spherical equivalent was -4.31 +/- 3.38 D
      (+0.25 to -9.50 diopters), and keratometry was 45.75 +/- 2.77 D (41.11 to 52.48
      diopters) postoperatively. Corneal astigmatism was 3.19 +/- 2.78 D (0.18 to 11.81
      diopters). Residual stromal bed thickness measured by optical coherence
      tomography showed values of 67.1 +/- 24.3 MUm (30 to 109 MUm). The statistical
      correlation by Spearman's test between the best-corrected visual acuity and the
      residual stromal bed thickness was 0.11 (P = 0.67). CONCLUSION: Deep anterior
      lamellar keratoplasty, in which manual dissection was performed using an
      instrument similar to that used to implant corneal rings, provided good visual
      and anatomical results.

PMID- 24881597
TI  - Saccadic eye movements in Parkinson's disease.
AB  - This review focuses on saccadic eye movement research in Parkinson's disease (PD)
      patients. Results from various studies related to Parkinson disease and saccades
      have been discussed in terms of various saccadic parameters like latency,
      amplitude, velocity and gain. Neural circuitry of saccadic eye movements and
      cognitive processes and it's relation with altered saccadic performance in
      Parkinson disease has been discussed here. This article also covers various
      research paradigms commonly used to study saccades. Effects of medication on
      saccadic parameters in PD patients have also been discussed along with the
      effects of deep brain stimulation of subthalamic nucleus on saccadic performance
      in PD patients. Literature review was done using online Pubmed search engine and
      National Medical Library. 

PMID- 24881596
TI  - New directions in the treatment of normal tension glaucoma.
AB  - Glaucoma is a progressive optic neuropathy that causes characteristic changes of
      the optic nerve and visual field in relation to intraocular pressure (IOP). It is
      now known that glaucoma can occur at statistically normal IOPs and prevalence
      studies have shown that normal tension glaucoma (NTG) is more common than
      previously thought. While IOP is believed to be the predominant risk factor in
      primary open angle glaucoma (POAG), IOP-independent risk factors, such as
      vascular dysregulation, are believed to play an important part in the
      pathogenesis of NTG. Though certain distinguishing phenotypic features of NTG
      have been reported, such as an increased frequency of disc hemorrhages, acquired
      pits of the optic nerve and characteristic patterns of disc cupping and visual
      field loss, there is much overlap of the clinical findings in NTG with POAG,
      suggesting that NTG is likely part of a continuum of open angle glaucomas.
      However, IOP modification is still the mainstay of treatment in NTG. As in
      traditional POAG, reduction of IOP can be achieved with the use of medications,
      laser trabeculoplasty or surgery. Studies now show that the choice of medication
      may also be important in determining the outcomes of these patients. Though it is
      likely that future treatment of NTG will involve modification of both IOP and IOP
      independent risk factors, current efforts to develop IOP-independent
      neuroprotective treatments have not yet proven to be effective in humans. 

PMID- 24881599
TI  - A preliminary study of the neuroprotective role of citicoline eye drops in
      glaucomatous optic neuropathy.
AB  - PURPOSE: To study the neuroprotective effect of topical citicoline. MATERIALS AND
      METHODS: Experimental phase to evaluate the ability of citicoline eye drops to
      reach the vitreous and the retina: The right eyes of 5 mice CD1 were treated with
      two drops per day for three days of citicoline 1% and 2% (OMK1, Omikron Italia
      s.r.l.), and then the vitreous was analyzed with the liquid chromatography and
      spectrometry mass (LC-MS/MS). Clinical phase to determine if topical citicoline
      is able to delay glaucoma progression, considering perimetric parameters and
      electro functional tests. Patients were randomized in two groups, OMK1 and OAG.
      The first group was treated with OMK1 three times per day, plus hypotensive
      therapy for two months and one month of wash out. The second group was treated
      only with hypotensive treatment for three months. RESULTS: LC-MS/MS detected the
      molecule very well, and only OMK1 showed systemic absorption. Thirty-four
      patients were enrolled, 16 in the OMK1 and 18 in the OAG group. Perimetric
      parameters showed a positive trend in individual eyes of patients in OMK1 group,
      but these values were not statistically significant in the whole group. Retinal
      ganglion cells function improved as shown by reduced P50 latency (P = 0.04) and
      increased P50-N95 amplitude (P < 0.0001) of pattern electroretinogram, up to 30
      days after the washout (P = 0.01; P = 0.002). Visual evoked potential and retino
      cortical time improvement regressed after 30 days of washout. In OAG group, there
      was any change during the follow-up. No adverse reactions were reported in both
      groups. CONCLUSIONS: Topical citicoline seems to have a neuroprotective action.

PMID- 24881600
TI  - Morphological changes in spectral domain optical coherence tomography guided
      bevacizumab injections in wet age-related macular degeneration, 12-months
      results.
AB  - PURPOSE: To describe retinal changes during Spectral Domain Optical Coherence
      Tomography (SD-OCT) guided bevacizumab treatment for neovascular age- related
      macular degeneration (AMD). SETTINGS AND DESIGN: Single center observational
      study. MATERIALS AND METHODS: We confirmed wet AMD in 47 eyes of 45 patients by
      fluorescein angiography and SD-OCT. After bevacizumab injection, we examined the
      patients at 4-week intervals. During each follow-up control, we performed SD-OCT
      and a complete ophthalmic examination. Criteria for reinjection were visual
      acuity loss of more than five ETDRS letters, and/or increase of central retinal
      thickness, sub-retinal fluid, intra-retinal fluid, pigment epithelium detachment.
      If reinjection criteria were not met, we advised the patient to return in 4
      weeks' time for the next scheduled follow-up. We used 3-dimensional SD-OCT to
      measure photoreceptor defects and sub-retinal fibrosis. The main efficacy
      endpoints were the SD-OCT measurements of the size of photoreceptor defects, the
      size of external membrane defects and the central retinal thickness. RESULTS:
      Over the 12 months study period, the percentage of scans in 3-D imaging mode
      showing visible defects of the junction between inner and outer segments of
      photoreceptors increased from 38.96 to 53.8%. The percentage of scans in 3-D
      imaging mode with visible sub-retinal fibrosis increased from 33 to 52% and mean
      central retinal thickness decreased from 333 MUm (96-900 MUm) to 272 MUm (P =
      0.011). CONCLUSION: In long-term anti- Vascular endothelial growth factor (VEGF)
      treatment for neovascular AMD, photoreceptor defects and fibrosis progress
      despite a decrease in central retinal thickness and improvements in visual
      acuity. We would encourage further discussion as to whether this is the natural
      course of the disease or a result of the treatment.

PMID- 24881601
TI  - Assessment of the central corneal thickness and intraocular pressure in premature
      and full-term newborns.
AB  - PURPOSE: To assess the central corneal thickness (CCT) and intraocular pressure
      (IOP) in premature and full-term newborns. MATERIALS AND METHODS: In this study,
      we evaluated measurements of CCT and IOP in 45 premature and 45 full-term
      newborns. IOP was determined with topical anesthesia using a Tono-Pen AVIA,
      applanation tonometer and a wire lid retractor in premature newborns undergoing
      screening for retinopathy. Full-term newborns were used as a control group. CCT
      was determined with a portable pachymeter after IOP measurements had been made in
      both groups. Because there was high correlation of CCT and IOP between right and
      left eyes, only the right eye data were used for further analyses. RESULTS: The
      mean gestational age was 31.5 +/- 2.7 weeks (ranging 25-35 weeks) and the mean
      age at measurement after birth was respectively 36.3 +/- 0.9 weeks (ranging 33-37
      weeks) in premature newborns and 38.2 +/- 0.7 weeks (ranging 38-41 weeks) and 42
      +/- 2.2 weeks (ranging 39-46 weeks) in full-term newborns. The mean IOP was 16.2
      +/- 2.7 mmHg (ranging 10-22 mmHg) in premature and 16.6 +/- 2.3 mmHg (ranging 10
      22 mmHg) in full-term newborns. The mean CCT was found 600 +/- 50 MUm (ranging
      515-790 MUm) in the premature group and 586 +/- 48 MUm (ranging 475-730 MUm) in
      the full-term group. Mean CCT was greater in premature newborns than in full-term
      newborns, but the difference between groups was not statistically significant (P
      = 0.7). Mean IOP measurement in two groups was found very similar and the
      difference also was not statistically significant (P = 0.27). There was no
      correlation between IOP and CCT, gestational age, gestational weight, age at
      measurement, weight at measurement neither right nor left eye in both groups in
      multiple regression analysis. CONCLUSION: We found that premature infants have
      slightly thicker corneas but no high IOP measurements than full-term newborns. It
      could be concluded that in premature at the mean gestational age of 36 weeks CCT
      is not different from that of full-term newborns.

PMID- 24881602
TI  - Demographic features of subjects with congenital glaucoma.
AB  - CONTEXT: Congenital glaucoma is a potentially blinding ocular disease of the
      childhood. Identification of the possible associated risk factors and may be
      helpful for prevention or early detection of this public health problem. AIMS: To
      demonstrate the demographic features of congenital glaucoma subjects. SETTING AND
      DESIGN: The charts of congenital glaucoma patients referred to Tamcelik Glaucoma
      Center were retrospectively reviewed through the dates of 2000 and 2013.
      MATERIALS AND METHODS: Analyzed data included diagnosis, age at first
      presentation, symptoms at first presentation, laterality of the disease, sex,
      presence of consanguinity, family history of congenital glaucoma, maturity of the
      fetus at delivery, and maternal age at conception. STATISTICAL ANALYSIS USED:
      Statistical Package for Social Sciences (SPSS) version 19.0 by IBM (SPSS Inc,
      Chicago, Illinois, USA) was used to compare the mean of continuous variables with
      Student's t-test and analysis of variance (ANOVA) and chi2 test was used to test
      differences in proportions of categorical variables. RESULTS: The data of 600
      eyes of 311 patients were analyzed. The distribution of primary and secondary
      congenital glaucoma among the patients were 63.3% (n = 197) and 36.7% (n = 114),
      respectively. Of the 311 patients, 57.2% (n = 178) were male and 42.8% (n = 133)
      were female. The overall frequency of bilateral disease was 92.3% (n = 287).
      Overall rate of consanguinity and positive family history was 45.3% (n = 141) and
      21.2% (n = 66), respectively. CONCLUSIONS: Bilateral disease in this study was
      more common than previously reported studies. Positive family history was more
      frequent in primary congenital glaucoma although not statistically significant.

PMID- 24881603
TI  - Ahmed glaucoma valve in eyes with preexisting episcleral encircling element.
AB  - BACKGROUND: To describe the use of Ahmed glaucoma valve (AGV) in the management
      of intractable glaucoma in eyes with a preexisting episcleral encircling element.
      MATERIALS AND METHODS: This is a retrospective, consecutive, noncomparative
      study. The study included 12 eyes of 12 patients with a preexisting episcleral
      encircling element that underwent implantation of silicone AGV to treat
      intractable glaucoma during January 2009 to September 2010. RESULTS: The mean
      patient age was 25.6 (standard deviation 17.1) years. Five (41.6%) patients were
      monocular. The indications for AGV were varied. The mean duration between
      placement of episcleral encircling element and implantation of AGV was 30.5
      (33.8) months. The mean follow-up was 37.4 (22.9) weeks. Preoperatively, the mean
      intraocular pressure (IOP) was 31.4 (7.9) mmHg and the mean antiglaucoma
      medications were 2.8. At the final postoperative follow-up, the mean IOP was 12.5
      (3.5) mmHg and the mean number of antiglaucoma medications was 0.8 (P < 0.001).
      The complications observed over the follow-up period did include corneal graft
      failure in three eyes, tube erosion in two eyes and rhegmatogenous retinal
      detachment in one eye. CONCLUSION: AGV is an effective option in the management
      of intractable glaucoma in eyes with a preexisting episcleral encircling element
      keeping in mind the possibility of significant postoperative complications.

PMID- 24881604
TI  - Contralateral intraocular pressure lowering effect of prostaglandin analogues.
AB  - BACKGROUND: Though the use of prostaglandin analogues (PGA) for reduction of
      intraocular pressure (IOP) has shown a marked increase, studies evaluating the
      contralateral effects of PGA are limited. AIMS: To evaluate if PGA treatment in
      one eye has an effect on the IOP of the untreated fellow eye. DESIGN:
      Retrospective study. MATERIALS AND METHODS: Thirty patients of open-angle
      glaucoma with no previous antiglaucoma treatment underwent 24-hour diurnal IOP
      phasing. They subsequently were started on a uniocular trial with PGA, and had
      office diurnal IOP measurements 6 weeks later. Twenty-four hour diurnal consisted
      of 8 IOP readings over 24 hours and office diurnal consisted of 4 IOP readings
      between 8 AM and 6 PM at 3 hourly intervals. STATISTICAL ANALYSIS: IOPs of the
      fellow eye during the office diurnal were compared with IOPs at similar time
      points during the 24-hour diurnal using paired t-tests. RESULTS: Mean (+/-
      standard deviation) IOP in the treated eye reduced (P < 0.001) from 17.17 +/- 3.2
      mm Hg at baseline to 13.7 +/- 2.4 mm Hg at 6 weeks, while that in the untreated
      eye reduced from 16.4 +/- 3.1 mm Hg to 14.8 +/- 2.7 mm Hg (P = 0.01). The
      decrease in IOP in the untreated fellow eye was statistically significant at 8 AM
      (2.7 mm Hg, P = 0.003) and 11 AM (2.3 mm Hg, P = 0.01) but not so at 2 PM (1.2 mm
      Hg, P = 0.10) and 5 PM (0.9 mm Hg, P = 0.19). The amount of IOP reduction in the
      untreated eye was significantly associated with the magnitude of IOP reduction in
      the treated eye (b = 0.69, P = 0.008). CONCLUSION: Uniocular PGA treatment tends
      to reduce the IOP of the untreated fellow eye.

PMID- 24881605
TI  - Liquefied after cataract and its surgical treatment.
AB  - AIMS: To describe liquefied after cataract (LAC) and its surgical management
      following an uneventful phacoemulsification with posterior chamber in-the-bag
      intraocular lens (IOL) implantation and continuous curvilinear capsulorrhexis
      (CCC). DESIGN: Interventional case series. MATERIALS AND METHODS: Eleven patients
      with LAC, following uneventful phacoemulsification with CCC and in-the-bag IOL
      implantation were enrolled. After the basic slit lamp examination, each case was
      investigated with Scheimpflug photography and ultrasound biomicroscopy (UBM).
      Each case was treated with capsular lavage. Biochemical composition of the milky
      fluid was evaluated and ring of anterior capsular opacity (ACO) was examined
      under electron microscope. RESULTS: All 11 cases presented with blurring of
      vision after 6-8 years of cataract surgery with IOL implantation. All cases had
      IOL microvacuoles, 360 degrees  anterior capsule, and anterior IOL surface touch
      along with ACO, ring of Soemmering, and posterior capsule distension filled with
      opalescent milky fluid with whitish floppy or crystalline deposits.
      Biochemically, the milky fluid contained protein (800 mg/dl), albumin (100
      mg/dl), sugar (105 mg/dl), and calcium (0.13%) and was bacteriologically sterile.
      Histologically, the dissected ACO showed fibrous tissue. All cases were
      successfully treated with capsular lavage with good visual recovery and with no
      complication. There was no recurrence of LAC during 2 years postoperative follow
      up in any of the cases. CONCLUSIONS: LAC is a late complication of standard
      cataract surgery. It may be a spectrum of capsular bag distension syndrome (CBDS)
      without shallow anterior chamber and secondary glaucoma. Capsular bag lavage is a
      simple and effective treatment for LAC and a safe alternative to neodymium-doped
      yttrium aluminum garnet (Nd-YAG) capsulotomy.

PMID- 24881606
TI  - Carboplatin loaded polymethylmethacrylate nano-particles in an adjunctive role in
      retinoblastoma: an animal trial.
AB  - PURPOSE: The purpose of the study is to compare the intra-vitreal concentrations
      of carboplatin, post peri-ocular injections of commercially available carboplatin
      (CAC) and a novel carboplatin loaded polymethylmethacrylate nanoparticulate
      carboplatin (NPC), in either eye, as a model system for treatment of advanced
      intra-ocular retinoblastoma (RB). DESIGN: Experimental, comparative, animal
      study. MATERIALS AND METHODS: Polymethylmethacrylate nanoparticles were prepared
      by free radical emulsion polymerization of methyl methacrylate in aqueous
      solution of carboplatin in the presence of surfactant sodium dodecyl sulfate and
      thermal initiator ammonium persulfate. 21 Sprague-Dawley rats, aged between 6
      weeks and 3 months were enrolled. The right eye of each rat was injected peri
      ocularly with CAC formulation (1 ml of 10 mg/ml) and the left eye with NPC (1 ml
      of 10 mg/ml), post-anesthesia, by an ophthalmologist trained in ocular oncology.
      Three rats each were euthanized on days 1, 3, 5, 7, 14, 28 and 42, post-injection
      and both eyes were carefully enucleated. Intra-vitreal concentrations of CAC and
      NPC were determined with Inductively Coupled Plasma Atomic Emission Spectroscopy.
      Analysis of data was done with paired t-test. RESULTS: The intra-vitreal
      concentration of carboplatin with NPC was ~3-4 times higher than with CAC in all
      animals, on all the days (P < 0.05). CONCLUSION: A higher trans-scleral
      permeability gradient is obtained with the novel nanoparticles than with the
      commercial drug, leading to sustained higher levels of carboplatin in the
      vitreous. Peri-ocular injection of NPC could thus have an adjuvant efficacy in
      the treatment for advanced clinical RB, specifically those with vitreous seeds.

PMID- 24881607
TI  - Post penetrating keratoplasty glaucoma: cumulative effect of quantifiable risk
      factors.
AB  - PURPOSE: To ascertain the incidence, identify risk factors and calculate
      cumulative effect of risk factors in patients developing glaucoma following
      optical penetrating keratoplasty. MATERIALS AND METHODS: We carried out
      retrospective analysis of 445 patients, those underwent optical PK and had a
      minimum follow up of 6 m. Data on post-operative intra-ocular pressure (IOP)
      recorded at 3, 6, 9, 12 and 18 m or more was analyzed. Various risk factors
      including age, sex, indications for penetrating keratoplasty, pre-existing
      glaucoma and type of surgical procedures performed were analyzed by using
      univariate analysis and logistic regression technique. RESULTS: Ninety (21%) of
      eyes developed post-PK glaucoma. On applying logistic regression, age, sex,
      indication of surgery, pre-existing glaucoma were found to be significant risk
      factors for the development of post-PK glaucoma (P < 0.05). Using logistic
      regression equation the cumulative risk of developing post-PK glaucoma in an
      individual patient can be calculated. CONCLUSIONS: Male patients, aged more than
      40 years, having opaque grafts as an indication and with pre-existing glaucoma
      were found to be higher risk of developing post-PK glaucoma. Patients at higher
      cumulative risk for development of post-PK glaucoma may be closely monitored
      during follow-up.

PMID- 24881608
TI  - Scleral-fixated intraocular lens implantation in microspherophakia.
AB  - BACKGROUND: In microspherophakia, abnormal laxity of the lenticular zonules leads
      to development of a spherical lens and possible subluxation. We evaluated long
      term results of lens removal with scleral-fixated intraocular lens (SFIOL)
      implantation in microspherophakia. MATERIALS AND METHODS: Case series. SF IOLs
      were implanted in four consecutive patients with bilateral microspherophakia
      (eight eyes [three with pupillary block and secondary glaucoma who underwent
      immediate surgery and five with only subluxation who underwent elective
      surgery]). Post-operative best-corrected visual acuity (BCVA), intraocular
      pressure (IOP) and lens position were evaluated periodically from day 1 to 18
      months. RESULTS: All patients were females (mean age 28 +/- 7.03 years). In group
      1 eyes (three eyes that presented with pupillary block), the mean BCVA improved
      from 0.008 decimals (preoperative) to 0.50 decimals (final post-operative visit);
      in group 2 eyes (the other five eyes), the mean BCVA improved from 0.12 +/- 0.21
      decimals to 0.73 +/- 0.14 decimals. The preoperative mean IOP (54.53 +/- 7.33
      mmHg) in group 1 eyes was significantly (P = 0.03) higher than that (16 +/- 4.30
      mm Hg) in group 2 eyes. At final post-operative visit, the mean IOP (11.67 +/-
      2.88 mmHg) in group 1 eyes was not significantly different from that in group 2
      eyes (13.0 +/- 3.08 mmHg). All SFIOLs were well- centred at the final visit. None
      of the patients encountered any peroperative or postoperative complications.
      CONCLUSIONS: SFIOLs may be an option for surgical management of
      microspherophakia.

PMID- 24881609
TI  - Outcomes of trabeculectomy in microspherophakia.
AB  - PURPOSE: To report the outcomes of trabeculectomy in eyes with glaucoma in
      microspherophakia. MATERIALS AND METHODS: In a retrospective non-comparative case
      series, we analyzed 29 eyes of 18 patients with glaucoma in microspherophakia,
      who underwent primary trabeculectomy between 1998 and 2012. Success was defined
      as complete if the intraocular pressure (IOP) was <= 21 and > 5 mm Hg without any
      antiglaucoma medication and qualified if IOP <= 21 and >5 mm Hg with or without
      antiglaucoma medications. Eyes not falling into qualified success criteria were
      labeled as failure. RESULTS: The median age at the time of trabeculectomy was 23
      years (inter quartile range: 12, 28). The mean IOP reduced from 31.1 +/- 8.6 mm
      Hg to 14.6 +/- 4.4 mm Hg after trabeculectomy over a median follow up of 77
      months (P < 0.001). The probability of complete success was 96% (95% CI: 77-99%)
      at one year, 88% (95% CI: 67-96%) at 2 years, which was maintained till 7 years
      and decreased to 79% (95% CI: 50-92%) at 8 years. The probability of qualified
      success was 100% till 7 years and decreased to 90% (95% CI: 47-98%) at 8 years.
      The median number of postoperative medications reduced from 2 to 0
      postoperatively (P < 0.001) . Five eyes (21%) developed post-operative shallow
      anterior chamber (AC) requiring anterior chamber reformation, with 2 of these
      eyes needing lensectomy for resolution of this complication. CONCLUSION: Primary
      trabeculectomy had good success rate in glaucoma associated with
      microspherophakia. Post-operative shallow AC was a frequent complication needing
      additional intervention.

PMID- 24881610
TI  - Topical nepafenac 0.1% alone versus prednisolone acetate 1% as postoperative anti
      inflammatory agents in small gauge vitrectomy.
AB  - AIM: To compare the efficacy of postoperative topical nepafenac (0.1%) with
      prednisolone acetate (1%) as anti-inflammatory agents in eyes undergoing
      Transscleral Sutureless Vitrectomy (TSV). SETTINGS AND DESIGN: Prospective,
      double-blind, randomized, single center clinical study. MATERIALS AND METHODS:
      Eighty eyes of 76 subjects, who underwent small gauge vitrectomy, were included
      in the study. The subjects who fulfilled the inclusion criteria were randomized
      to either topical nepafenac only (Group 1) or prednisolone acetate only (Group
      2), to be used as postoperative anti-inflammatory agents. The subjects were
      reviewed on days 1, 30, and 90. Ocular and adnexal inflammation was appropriately
      graded using the standardized classification. Grading of ocular pain was done on
      the Visual Analog Scale (VAS). STATISTICAL ANALYSIS: The Wilcoxon rank-sum test,
      using two-sided analysis, was used. RESULTS: During the follow-up, both Group 1
      and Group 2 did not have a significant difference related to the grade of the
      anterior chamber inflammation (P > 0.05) or adnexal inflammation (P > 0.05). Pain
      perception was less in the subjects in Group 1 as compared to subjects in Group
      2, but was not statistically significant (P > 0.05). CONCLUSION: Postoperative
      topical nepafenac was non-inferior to prednisolone acetate in reducing
      postoperative ocular inflammation in eyes undergoing TSV.

PMID- 24881611
TI  - Influence of disc area on retinal nerve fiber layer thickness measurement by
      spectral domain optical coherence tomography.
AB  - BACKGROUND: To examine the effect of optic disc area on peripapillary RNFLT
      (retinal nerve fiber layer thickness) measurement at circle diameter of 3.4 mm
      around optic nerve head using spectral OCT/SLO (Optical coherence
      tomography/scanning laser ophthalmoscope). MATERIALS AND METHODS: In this
      prospective, cross sectional study, one hundred and two eyes of 102 normal
      subjects underwent RNFLT and disc area measurement using spectral OCT/SLO. Based
      on disc area, subjects were divided into three groups i.e., <3 mm2 (32 eyes), 3-4
      mm2 (36 eyes) and >4 mm2 (34 eyes). The effect of disc area on RNFLT parameters
      was analyzed using linear regression analysis. RESULTS: The mean and quadrant
      RNFLT did not show significant correlation with disc area in subjects with disc
      area of <4 mm2, however in eyes with disc area >4 mm2, average RNFLT, superior
      and temporal quadrant RNFLT showed negative correlation with disc area, which was
      statistically significant (P = 0.004, P = 0.005 and P = 0.002, respectively).
      CONCLUSION: In healthy eyes of disc area <4 mm2, disc size does not appear to
      affect peripapillary RNFLT measurement by spectral OCT/SLO. Average, superior and
      temporal quadrant RNFLT measurements were inversely proportional to disc area in
      eyes with disc area >4 mm2. Hence, RNFLT measurement by OCT in eyes with optic
      disc area of >4 mm2 should be interpreted carefully.

PMID- 24881612
TI  - Anterior segment optical coherence tomography documentation of a case of
      topiramate induced acute angle closure.
AB  - We present a case report of a 31-year-old female patient who presented to us with
      a 1 day history of acute bilateral eye pain, blurred vision and headache. She was
      found to have a myopic shift, raised intraocular pressure (IOP) and shallow
      anterior chambers in both eyes. She had been commenced on oral topiramate 1 week
      previously. A number of investigations, including anterior segment optical
      coherence tomography (AS-OCT) were done and a diagnosis of topiramate induced
      bilateral acute angle closure (TiAAC) was made. Topiramate was discontinued and
      she was managed with topical and oral antiglaucoma medications, topical steroids
      and cyclopegics. Her symptoms subsided dramatically at the next follow-up. The AS
      OCT documentation revealed lucidly the improvement in her anterior chamber depth
      and anterior chamber angle parameters. Her IOP decreased, her myopic shift showed
      reversal and her AS-OCT findings revealed gross improvement in all the parameters
      angle opening distance, trabecular iris space area and scleral spur angle. This
      case report clearly shows with AS OCT documentation the changes which occur in
      the anterior segment in a case of TiAAC. 

PMID- 24881613
TI  - Encephalocraniocutaneous lipomatosis: a case report and review of the literature.
AB  - Encephalocraniocutaneous lipomatosis (ECCL) is a rare, sporadic congenital
      neurocutaneous disorder that characteristically involves ectomesodermal tissues,
      such as skin, eyes, and central nervous system. A 3-day-old girl presented with
      swelling in her right eye since birth. Ocular examination of the right eye showed
      hypertrophy of bulbar conjunctiva with limbal dermoid, clouding of cornea, and
      atypical upper eyelid coloboma. The left eye showed conjunctival congestion and
      corneal vascularization. Dermatological examination showed alopecia, nevus
      psiloliparus, focal dermal hypoplasia on forehead, multiple focal aplastic
      lesions on the scalp, skin tag at canthus, and lipoma in the fronto-temporal
      region. Imaging revealed calcification of the right globe, hydrocephalus,
      agenesis of corpus callosum, multiple intracranial cysts, calcification, and
      lipomas. The constellation of these clinical and the imaging findings led to a
      diagnosis of encephalocraniocutaneous lipomatosis. This case report and review of
      the literature is presented to provide a synopsis of problems likely to be
      encountered by an ophthalmologist who treats patients with ECCL. 

PMID- 24881614
TI  - ALK negative inflammatory myofibroblastic tumor of the orbit: a masquerading
      entity.
AB  - Inflammatory myofibroblastic tumor is a biologically distinct neoplasm of
      intermediate grade, which can affect every possible tissue of the human body. It
      is a 'masquerading tumor' as the presenting complaints vary with the affected
      site. Occurrence of this tumor as an orbital mass is rare and is challenging for
      both the clinician as well as the pathologist, due to a varied number of lesions
      sharing a similar picture clinically and histologically. We discuss a rare case
      of inflammatory myofibroblastic tumor presenting as an orbital mass and the
      importance of immunohistochemistry in arriving at the diagnosis, which helps
      dictate the treatment and prognosis of the patient. 

PMID- 24881615
TI  - Prosthetic rehabilitation after orbital exenteration: a case series.
AB  - Orbital exenteration is executed by the ophthalmic surgeon to treat various
      neoplasms or non-malignant diseases. But it leads to several functional, esthetic
      and psychological problems for the patients. Orbital prosthesis is a good
      alternative for cosmetic and psychological rehabilitation, if reconstructive
      surgery is not possible or not desired by the patient. In the following article,
      different materials and retentive aids for fabrication of an orbital prosthesis
      given in the literature along with few novel methods have been discussed for four
      patients who underwent orbital exenteration. Factors that an ophthalmic surgeon
      should consider during surgery, which may later on help the prosthodontist to
      obtain good cosmetic results, are also discussed briefly. Remarkable results can
      be obtained if both work as a team for one common goal i.e. improvement of
      quality of life of the patient after orbital exenteration. 

PMID- 24881616
TI  - Keratoconjunctivitis caused by an unusual retained conjunctival foreign body: a
      frequently unrecognized entity.
AB  - PURPOSE: The purpose of this study is to describe a case series of
      keratoconjunctivitis caused by a retained bindi (dot) in six children who
      presented to a tertiary eye care facility in Southern India. PATIENTS AND
      METHODS: Over a period of 11 years (January 2000 and January 2012), six children
      (all female, ranging in age from 6 months to 3 years) were diagnosed with ocular
      manifestations subsequent to a retained bindi. RESULTS: All patients presented
      with redness, photophobia, extensive lacrimation, and blepharospasm. Two patients
      presented with mucopurulent conjunctivitis, three patients with suppurative
      keratitis and one patient presented with corneal epithelial defect. After removal
      of the foreign body the response to topical antibiotics was good in five of six
      cases, whereas one patient required therapeutic keratoplasty. CONCLUSIONS: Young
      children presenting with unilateral keratitis and conjunctivitis should alert the
      clinician to the possibility of a retained foreign body in the eye.

PMID- 24881617
TI  - Cortical visual loss in posterior reversible encephalopathy syndrome in late
      postpartum eclampsia: case series.
AB  - The purpose of this study was to determine the prevalence of visual disturbances
      in patients with posterior reversible encephalopathy syndrome (PRES) associated
      with late postpartum eclampsia. We retrospectively reviewed the clinical records
      of late postpartum eclampsia patients with features of PRES for the presence of
      visual disturbances and location of radiological abnormalities. We found a higher
      prevalence of cortical visual loss in patients with PRES associated with late
      postpartum eclampsia. Bilateral symmetrical vasogenic edema of the parieto
      occipital lobe was the most common magnetic resonance imaging (MRI) abnormality
      noted. No significant differences were observed in the extent of edema in
      patients with and without visual loss. 

PMID- 24881618
TI  - A new rosette in retinoblastoma.
AB  - Retinoblastoma, the most common primary malignant intraocular tumor of childhood
      is a great success story in pediatric and ocular oncology. Pathology of
      retinoblastoma is important to guide the treatment modalities. Differentiated
      retinoblastoma is commonly seen in younger age group. Since a hundred years, we
      have been observing two typical true rosettes in retinoblastoma in the form of
      Flexner-Wintersteiner (FW) and Homer Wright (HW) rosettes and in many occasions
      pseudorosettes have been documented. In the present case report, a third new type
      of rosette was identified in a differentiated retinoblastoma which had an unusual
      anterior segment involvement. 

PMID- 24881619
TI  - Successful treatment of fusarium keratitis after photo refractive keratectomy.

PMID- 24881620
TI  - Chemo-paralysis for removal of anterior chamber motile parasite.

PMID- 24881621
TI  - Pseudomonas aeruginosa endophthalmitis masquerading as chronic uveitis.

PMID- 24881622
TI  - Endophthalmitis and clear corneal cataract incisions.

PMID- 24881623
TI  - Risk factors for intraocular pressure rise following phacoemulsification.

PMID- 24881625
TI  - Regulation of the immediate-early genes of white spot syndrome virus by
      Litopenaeus vannamei kruppel-like factor (LvKLF).
AB  - Kruppel-like factors (KLFs) belong to a subclass of Cys2/His2 zinc-finger DNA
      binding proteins, and act as important regulators with diverse roles in cell
      growth, proliferation, differentiation, apoptosis and tumorigenesis. Our previous
      research showed that PmKLF from Penaeus monodon is crucial for white spot
      syndrome virus (WSSV) infection, yet the mechanisms by which PmKLF influences
      WSSV infection remain unclear. This study cloned KLF from Litopenaeus vannamei
      (LvKLF), which had 93% similarity with PmKLF. LvKLF formed a dimer via the C
      terminal zinc-finger motif. Knockdown of LvKLF expression by dsRNA injection in
      WSSV-challenged shrimps was found to significantly inhibit the transcription of
      two important immediate-early (IE) genes, IE1 and WSSV304, and also reduced WSSV
      copy numbers. Moreover, reporter assays revealed that the promoter activities of
      these two WSSV IE genes were substantially enhanced by LvKLF. Mutations
      introduced in the promoter sequences of IE1 and WSSV304 were shown to abolish
      LvKLF activation of promoter activities; and an electrophoretic mobility shift
      assay demonstrated that LvKLF binds to putative KLF-response elements (KRE) in
      the promoters. Taken together, these results indicate that LvKLF transcriptional
      regulation of key IE genes is critical to WSSV replication. 

PMID- 24881624
TI  - Cardiovascular and hemodynamic effects of glucagon-like peptide-1.
AB  - Glucagon-like peptide-1 (GLP-1) is an incretin hormone that has been shown to
      have hemodynamic and cardioprotective capacity in addition to its better
      characterized glucoregulatory actions. Because of this, emerging research has
      focused on the ability of GLP-1 based therapies to drive myocardial substrate
      selection, enhance cardiac performance and regulate heart rate, blood pressure
      and vascular tone. These studies have produced consistent and reproducible
      results amongst numerous laboratories. However, there are obvious disparities in
      findings obtained in small animal models versus those of higher mammals. This
      species dependent discrepancy calls to question, the translational value of
      individual findings. Moreover, few studies of GLP-1 mediated cardiovascular
      action have been performed in the presence of a pre-existing comorbidities (e.g.
      obesity/diabetes) which limits interpretation of the effectiveness of incretin
      based therapies in the setting of disease. This review addresses cardiovascular
      and hemodynamic potential of GLP-1 based therapies with attention to species
      specific effects as well as the interaction between therapies and disease. 

PMID- 24881626
TI  - Effect of exacerbation frequency on body composition and serum ghrelin and
      adiponectin concentrations in patients with chronic obstructive pulmonary
      disease.
AB  - INTRODUCTION Exacerbations affect the natural history of chronic obstructive
      pulmonary disease (COPD). OBJECTIVES: The aim of the study was to evaluate the
      effect of exacerbation frequency in COPD on body composition and systemic
      inflammation assessed by the measurement of serum adiponectin and ghrelin
      concentrations. PATIENTS AND METHODS: The study group included 152 patients with
      COPD. Body composition was assessed by bioimpedance. Fasting serum adiponectin
      and ghrelin concentrations were evaluated by enzyme-linked immunosorbent assays.
      RESULTS: Of the 152 patients, 60 did not report any exacerbation in the last 12
      months, 53 had 1 exacerbation, and 39 had more than 1 exacerbation. The mean
      number of exacerbations in the whole group was 1.04 +/-1.3 per patient per year
      and increased with the increasing degree of airway obstruction. Patients with
      exacerbations had a lower fat-free mass (FFM) index, lower total body water, and
      lower resting metabolic rate compared with patients without exacerbations (18.3
      +/-2.5 kg/m2 vs. 19.3 +/-2.7 kg/m2; 36.9 +/-8.1 kg vs. 40.2 +/-8.0 kg; and 1482.8
      +/-301.1 kcal vs. 1616.0 +/-322.0 kcal; respectively). The adiponectin
      concentration was higher in patients with more than 1 exacerbation than in those
      with 1 or no exacerbations (14.5 +/-8.6 mg/l vs. 11.2 +/-7.6 mg/l, P <0.05). We
      observed significant negative correlations between the number of exacerbations
      and the muscle mass index, FFM index, total body water, resting metabolic rate,
      and adiponectin concentration in the whole group. CONCLUSIONS: Exacerbations
      affect body composition in patients with COPD. Patients with frequent
      exacerbations have more enhanced systemic inflammation. Assessment of the body
      composition and systemic inflammation should be part of the routine management of
      patients with COPD.

PMID- 24881628
TI  - Abstracts of the young investigators award of the belgian society of internal
      medicine, congress 9 - 10 december 2005, le marais, brussels.

PMID- 24881627
TI  - Determinants of HIV counseling and testing uptake among individuals in long-term
      sexual relationships in Uganda.
AB  - INTRODUCTION: Studies show that HIV counseling and testing (HCT) can improve
      linkage to HIV prevention, care and treatment services. However, uptake of HCT
      among couples remains low in most settings. We investigated the determinants of
      HCT uptake among individuals in long-term relationships in two districts in
      Uganda. METHODS: This case-control study was conducted among 787 (400 in Kampala
      and 387 in Soroti) individuals in long-term sexual relationships, aged 18-54
      years, using interviewer-administered questionnaires. Cases were individuals who
      had ever tested for HIV (selected from health facility records and traced in the
      community for interview) while controls were individuals who had never tested for
      HIV, identified from the same community as the cases. Data were collected on
      sociodemographic and behavioral characteristics; entered into FoxPro and analyzed
      using STATA version 12.1. We performed multivariable logistic regression to
      estimate the odds ratio (OR) and 95% Confidence Intervals (95%CI) associated with
      prior HCT and couples' HCT uptake, controlling for suspected confounders.
      RESULTS: Of the 787 participants, 522 had ever tested for HIV (cases) while 265
      had never tested for HIV (controls). Compared to those that had never tested for
      HIV, those that had ever tested for HIV were significantly more likely to be
      females (Adj. OR=3.23, 95%CI: 2.27, 4.60), to be 25-29 years old (Adj. OR=2.15,
      95%CI: 1.32, 3.50), to report exposure to a couples' HCT promotional campaign
      (Adj. OR=2.01, 95%CI: 1.30, 3.10) and to believe that HIV discordance is possible
      among married couples (Adj. OR=1.77, 95%CI: 1.20, 2.63). Compared to individuals
      that had ever received individual HCT, those that had ever received couples' HCT
      were significantly more likely to report prior discussion of HIV testing with
      partner (Adj. OR=4.35, 95%CI: 2.61, 7.28) and to be residents of Soroti district
      (Adj. OR=6.01, 95%CI: 3.74, 9.65). CONCLUSION: Prior HCT was significantly
      associated with female gender and exposure to a couples' HCT promotional campaign
      while prior couples' HCT was significantly associated with prior discussion of
      HIV testing with partner. To increase HIV testing among couples, these findings
      suggest a need for HCT promotional campaigns that promote communication about HCT
      between partners.

PMID- 24881629
TI  - Acupuncture for allergic disease therapy--the current state of evidence.
AB  - This review summarizes current evidence for acupuncture treatment of allergies.
      Several randomized controlled trials have demonstrated a specific effect of
      acupuncture for allergic rhinitis; while a few studies have shown positive
      effects for atopic dermatitis, asthma and itch. Specifically for allergic
      rhinitis and asthma, acupuncture may be cost-effective in terms of money spent
      per quality-of-life gained. Acupuncture plays an increasingly important role as
      an evidence-based therapy for allergy relief and can be recommended as adjunct
      therapy for allergic rhinitis. Future randomized controlled trials need to
      further explore acupuncture efficacy for the treatment of itch, atopic dermatitis
      and asthma. More experimental research is also needed to investigate mechanisms
      of action underlying acupuncture for allergy relief.

PMID- 24881630
TI  - Criminal justice and behavioral health care costs of mental health court
      participants: a six-year study.
AB  - OBJECTIVE: This study examined whether there were differences in costs for mental
      health court (MHC) participants and a matched comparison group for three years
      after a target arrest. METHODS: Data from the MacArthur Mental Health Court
      Study, the first multisite study of MHCs, were used to compare behavioral health
      treatment and criminal justice costs for MHC participants and a matched group
      (using coarsened exact matching) of jail detainees who were not enrolled in an
      MHC but who received jail-based psychiatric services in the same cities. Cost
      data for three years before and after a target arrest were calculated separately
      for each year and for each participant at three sites of the multisite study-296
      MHC participants and 386 matched jail detainees. High-cost MHC participants were
      identified. RESULTS: Total annual costs for MHC participants averaged $4,000 more
      for all three follow-up years. The additional costs resulted from treatment
      costs, which were not offset by criminal justice cost savings. The highest-cost
      MHC participants were those with diagnoses of co-occurring substance use
      disorders and those who had more arrest incarceration days before their target
      arrest. Separate analyses determined that the higher average costs were not the
      result of outlier cases. CONCLUSIONS: Participation in an MHC may not result in
      total cost savings in the three years after enrollment. To become more efficient
      and to serve participants with the greatest needs, MHCs need to more effectively
      define the target group for intervention.

PMID- 24881632
TI  - Pedicle screw fixation in minimally invasive transforaminal lumbar interbody
      fusion.

PMID- 24881633
TI  - Variations in cost calculations in spine surgery cost-effectiveness research.
AB  - OBJECT: Cost-effectiveness research in spine surgery has been a prominent focus
      over the last decade. However, there has yet to be a standardized method
      developed for calculation of costs in such studies. This lack of a standardized
      costing methodology may lead to conflicting conclusions on the cost-effectiveness
      of an intervention for a specific diagnosis. The primary objective of this study
      was to systematically review all cost-effectiveness studies published on spine
      surgery and compare and contrast various costing methodologies used. METHODS: The
      authors performed a systematic review of the cost-effectiveness literature
      related to spine surgery. All cost-effectiveness analyses pertaining to spine
      surgery were identified using the cost-effectiveness analysis registry database
      of the Tufts Medical Center Institute for Clinical Research and Health Policy,
      and the MEDLINE database. Each article was reviewed to determine the study
      subject, methodology, and results. Data were collected from each study, including
      costs, interventions, cost calculation method, perspective of cost calculation,
      and definitions of direct and indirect costs if available. RESULTS: Thirty-seven
      cost-effectiveness studies on spine surgery were included in the present study.
      Twenty-seven (73%) of the studies involved the lumbar spine and the remaining 10
      (27%) involved the cervical spine. Of the 37 studies, 13 (35%) used Medicare
      reimbursements, 12 (32%) used a case-costing database, 3 (8%) used cost-to-charge
      ratios (CCRs), 2 (5%) used a combination of Medicare reimbursements and CCRs, 3
      (8%) used the United Kingdom National Health Service reimbursement system, 2 (5%)
      used a Dutch reimbursement system, 1 (3%) used the United Kingdom Department of
      Health data, and 1 (3%) used the Tricare Military Reimbursement system. Nineteen
      (51%) studies completed their cost analysis from the societal perspective, 11
      (30%) from the hospital perspective, and 7 (19%) from the payer perspective. Of
      those studies with a societal perspective, 14 (38%) reported actual indirect
      costs. CONCLUSIONS: Changes in cost have a direct impact on the value equation
      for concluding whether an intervention is cost-effective. It is essential to
      develop a standardized, accurate means of calculating costs. Comparability and
      transparency are essential, such that studies can be compared properly and policy
      makers can be appropriately informed when making decisions for our health care
      system based on the results of these studies.

PMID- 24881634
TI  - Improving discharge data fidelity for use in large administrative databases.
AB  - OBJECT: Large administrative databases have assumed a major role in population
      based studies examining health care delivery. Lumbar fusion surgeries
      specifically have been scrutinized for rising rates coupled with ill-defined
      indications for fusion such as stenosis and spondylosis. Administrative databases
      classify cases with the International Classification of Diseases, Ninth Revision,
      Clinical Modification (ICD-9-CM). The ICD-9-CM discharge codes are not designated
      by surgeons, but rather are assigned by trained hospital medical coders. It is
      unclear how accurately they capture the surgeon's indication for fusion. The
      authors first sought to compare the ICD-9-CM code(s) assigned by the medical
      coder according to the surgeon's indication based on a review of the medical
      chart, and then to elucidate barriers to data fidelity. METHODS: A retrospective
      review was undertaken of all lumbar fusions performed in the Department of
      Neurosurgery at the authors' institution between August 1, 2011, and August 31,
      2013. Based on this review, the indication for fusion in each case was
      categorized as follows: spondylolisthesis, deformity, tumor, infection,
      nonpathological fracture, pseudarthrosis, adjacent-level degeneration, stenosis,
      degenerative disc disease, or disc herniation. These surgeon diagnoses were
      compared with the primary ICD-9-CM codes that were generated by the medical
      coders and submitted to administrative databases. A follow-up interview with the
      hospital's coders and coding manager was undertaken to review causes of error and
      suggestions for future improvement in data fidelity. RESULTS: There were 178
      lumbar fusion operations performed in the course of 170 hospital admissions.
      There were 44 hospitalizations in which fusion was performed for tumor,
      infection, or nonpathological fracture. Of these, the primary diagnosis matched
      the surgical indication for fusion in 98% of cases. The remaining 126
      hospitalizations were for degenerative diseases, and of these, the primary ICD-9
      CM diagnosis matched the surgeon's diagnosis in only 61 (48%) of 126 cases of
      degenerative disease. When both the primary and all secondary ICD-9-CM diagnoses
      were considered, the indication for fusion was identified in 100 (79%) of 126
      cases. Still, in 21% of hospitalizations, the coder did not identify the surgical
      diagnosis, which was in fact present in the chart. There are many different
      causes of coding inaccuracy and data corruption. They include factors related to
      the quality of documentation by the physicians, coder training and experience,
      and ICD code ambiguity. CONCLUSIONS: Researchers, policymakers, payers, and
      physicians should note these limitations when reviewing studies in which hospital
      claims data are used. Advanced domain-specific coder training, increased
      attention to detail and utilization of ICD-9-CM diagnoses by the surgeon, and
      improved direction from the surgeon to the coder may augment data fidelity and
      minimize coding errors. By understanding sources of error, users of these large
      databases can evaluate their limitations and make more useful decisions based on
      them.

PMID- 24881631
TI  - Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia.
AB  - BACKGROUND: In patients with chronic lymphoid leukemia (CLL) or small lymphocytic
      lymphoma (SLL), a short duration of response to therapy or adverse cytogenetic
      abnormalities are associated with a poor outcome. We evaluated the efficacy of
      ibrutinib, a covalent inhibitor of Bruton's tyrosine kinase, in patients at risk
      for a poor outcome. METHODS: In this multicenter, open-label, phase 3 study, we
      randomly assigned 391 patients with relapsed or refractory CLL or SLL to receive
      daily ibrutinib or the anti-CD20 antibody ofatumumab. The primary end point was
      the duration of progression-free survival, with the duration of overall survival
      and the overall response rate as secondary end points. RESULTS: At a median
      follow-up of 9.4 months, ibrutinib significantly improved progression-free
      survival; the median duration was not reached in the ibrutinib group (with a rate
      of progression-free survival of 88% at 6 months), as compared with a median of
      8.1 months in the ofatumumab group (hazard ratio for progression or death in the
      ibrutinib group, 0.22; P<0.001). Ibrutinib also significantly improved overall
      survival (hazard ratio for death, 0.43; P=0.005). At 12 months, the overall
      survival rate was 90% in the ibrutinib group and 81% in the ofatumumab group. The
      overall response rate was significantly higher in the ibrutinib group than in the
      ofatumumab group (42.6% vs. 4.1%, P<0.001). An additional 20% of ibrutinib
      treated patients had a partial response with lymphocytosis. Similar effects were
      observed regardless of whether patients had a chromosome 17p13.1 deletion or
      resistance to purine analogues. The most frequent nonhematologic adverse events
      were diarrhea, fatigue, pyrexia, and nausea in the ibrutinib group and fatigue,
      infusion-related reactions, and cough in the ofatumumab group. CONCLUSIONS:
      Ibrutinib, as compared with ofatumumab, significantly improved progression-free
      survival, overall survival, and response rate among patients with previously
      treated CLL or SLL. (Funded by Pharmacyclics and Janssen; RESONATE
      ClinicalTrials.gov number, NCT01578707.).

PMID- 24881635
TI  - Cost-effectiveness of lumbar discectomy and single-level fusion for
      spondylolisthesis: experience with the NeuroPoint-SD registry.
AB  - OBJECT: There is significant practice variation and uncertainty as to the value
      of surgical treatments for lumbar spine disorders. The authors' aim was to
      establish a multicenter registry to assess the efficacy and costs of common
      lumbar spinal procedures by using prospectively collected outcomes. METHODS: An
      observational prospective cohort study was completed at 13 academic and community
      sites. Patients undergoing single-level fusion for spondylolisthesis or single
      level lumbar discectomy were included. The 36-Item Short Form Health Survey (SF
      36) and Oswestry Disability Index (ODI) data were obtained preoperatively and at
      1, 3, 6, and 12 months postoperatively. Power analysis estimated a sample size of
      160 patients: lumbar disc (125 patients) and lumbar listhesis (35 patients). The
      quality-adjusted life year (QALY) data were calculated using 6-dimension utility
      index scores. Direct costs and complication costs were estimated using Medicare
      reimbursement values from 2011, and indirect costs were estimated using the human
      capital approach with the 2011 US national wage index. Total costs equaled
      $14,980 for lumbar discectomy and $43,852 for surgery for lumbar
      spondylolisthesis. RESULTS: There were 198 patients enrolled over 1 year. The
      mean age was 46 years (49% female) for lumbar discectomy (n = 148) and 58.1 years
      (60% female) for lumbar spondylolisthesis (n = 50). Ten patients with disc
      herniation (6.8%) and 1 with listhesis (2%) required repeat operation at 1 year.
      The overall 1-year follow-up rate was 88%. At 30 days, both lumbar discectomy and
      single-level fusion procedures were associated with significant improvements in
      ODI, visual analog scale, and SF-36 scores (p = 0.0002), which persisted at the 1
      year evaluation (p < 0.0001). By 1 year, more than 80% of patients in each cohort
      who were working preoperatively had returned to work. Lumbar discectomy was
      associated with a gain of 0.225 QALYs over the 1-year study period ($66,578/QALY
      gained). Lumbar spinal fusion for Grade I listhesis was associated with a gain of
      0.195 QALYs over the 1-year study period ($224,420/QALY gained). CONCLUSIONS:
      This national spine registry demonstrated successful collection of high-quality
      outcomes data for spinal procedures in actual practice. These data are useful for
      demonstrating return to work and cost-effectiveness following surgical treatment
      of single-level lumbar disc herniation or spondylolisthesis. One-year cost per
      QALY was obtained, and this cost per QALY is expected to improve further by 2
      years. This work sets the stage for real-world analysis of the value of health
      interventions.

PMID- 24881636
TI  - Cost-effectiveness analysis in minimally invasive spine surgery.
AB  - OBJECT: Medical care has been evolving with the increased influence of a value
      based health care system. As a result, more emphasis is being placed on ensuring
      cost-effectiveness and utility in the services provided to patients. This study
      looks at this development in respect to minimally invasive spine surgery (MISS)
      costs. METHODS: A literature review using PubMed, the Cost-Effectiveness Analysis
      (CEA) Registry, and the National Health Service Economic Evaluation Database (NHS
      EED) was performed. Papers were included in the study if they reported costs
      associated with minimally invasive spine surgery (MISS). If there was no mention
      of cost, CEA, cost-utility analysis (CUA), quality-adjusted life year (QALY),
      quality, or outcomes mentioned, then the article was excluded. RESULTS: Fourteen
      studies reporting costs associated with MISS in 12,425 patients (3675 undergoing
      minimally invasive procedures and 8750 undergoing open procedures) were
      identified through PubMed, the CEA Registry, and NHS EED. The percent cost
      difference between minimally invasive and open approaches ranged from 2.54% to
      33.68%-all indicating cost saving with a minimally invasive surgical approach.
      Average length of stay (LOS) for minimally invasive surgery ranged from 0.93 days
      to 5.1 days compared with 1.53 days to 12 days for an open approach. All studies
      reporting EBL reported lower volume loss in an MISS approach (range 10-392.5 ml)
      than in an open approach (range 55-535.5 ml). CONCLUSIONS: There are currently an
      insufficient number of studies published reporting the costs of MISS. Of the
      studies published, none have followed a standardized method of reporting and
      analyzing cost data. Preliminary findings analyzing the 14 studies showed both
      cost saving and better outcomes in MISS compared with an open approach. However,
      more Level I CEA/CUA studies including cost/QALY evaluations with specifics of
      the techniques utilized need to be reported in a standardized manner to make more
      accurate conclusions on the cost effectiveness of minimally invasive spine
      surgery.

PMID- 24881637
TI  - Perioperative outcomes, complications, and costs associated with lumbar spinal
      fusion in older patients with spinal stenosis and spondylolisthesis.
AB  - OBJECT: The purpose of this study was to quantify the perioperative outcomes,
      complications, and costs associated with posterolateral spinal fusion (PSF) among
      Medicare enrollees with lumbar spinal stenosis (LSS) and/or spondylolisthesis by
      using a national Medicare claims database. METHODS: A 5% systematic sample of
      Medicare claims data (2005-2009) was used to identify outcomes in patients who
      had undergone PSF for a diagnosis of LSS and/or spondylolisthesis. Patients
      eligible for study inclusion also required a minimum of 2 years of follow-up and
      a claim history of at least 12 months prior to surgery. RESULTS: A final cohort
      of 1672 patients was eligible for analysis. Approximately half (50.7%) had LSS
      only, 10.2% had spondylolisthesis only, and 39.1% had both LSS and
      spondylolisthesis. The average age was 71.4 years, and the average length of stay
      was 4.6 days. At 3 months and 1 and 2 years postoperatively, the incidence of
      spine reoperation was 10.9%, 13.3%, and 16.9%, respectively, whereas readmissions
      for complications occurred in 11.1%, 17.5%, and 24.9% of cases, respectively. At
      2 years postoperatively, 36.2% of patients had either undergone spine reoperation
      and/or received an epidural injection. The average Medicare payment was $36,230
      +/- $17,020, $46,840 +/- $31,350, and $61,610 +/- $46,580 at 3 months, 1 year,
      and 2 years after surgery, respectively. CONCLUSIONS: The data showed that 1 in 6
      elderly patients treated with PSF for LSS or spondylolisthesis underwent
      reoperation on the spine within 2 years of surgery, and nearly 1 in 4 patients
      was readmitted for a surgery-related complication. These data highlight several
      potential areas in which improvements may be made in the effective delivery and
      cost of surgical care for patients with spinal stenosis and spondylolisthesis.

PMID- 24881639
TI  - Introduction: Costs and benefits of modern-day spine care.

PMID- 24881640
TI  - Clinical and methodological confounders in assessing the cerebellar cognitive
      affective syndrome in adult patients with posterior fossa tumours.
AB  - The cerebellar cognitive affective syndrome (CCAS) was first described by
      Schmahmann and Sherman as a constellation of symptoms including dysexecutive
      syndrome, spatial cognitive deficit, linguistic deficits and behavioural
      abnormalities in patients with a lesion in the cerebellum with otherwise normal
      brain. Neurosurgical patients with cerebellar tumours constitute one of the
      cohorts in which the CCAS has been described. In this paper, we present a
      critical review of the literature of this syndrome in neurosurgical patients.
      Thereafter, we present a prospective clinical study of 10 patients who underwent
      posterior fossa tumour resection and had a detailed post-operative
      neuropsychological, neuropsychiatric and neuroradiological assessment. Because
      our findings revealed a large number of perioperative neuroradiological
      confounding variables, we reviewed the neuroimaging of a further 20 patients to
      determine their prevalence. Our literature review revealed that study design,
      methodological quality and sometimes both diagnostic criteria and findings were
      inconsistent. The neuroimaging study (pre-operative, n = 10; post-operative, n =
      10) showed very frequent neuroradiological confounding complications (e.g.
      hydrocephalus; brainstem compression; supratentorial lesions and post-operative
      subdural hygroma); the impact of such features had largely been ignored in the
      literature. Findings from our clinical study showed various degree of deficits in
      neuropsychological testing (n = 1, memory; n = 3, verbal fluency; n = 3,
      attention; n = 2, spatial cognition deficits; and n = 1, behavioural changes),
      but no patient had full-blown features of CCAS. Our study, although limited,
      finds no robust evidence of the CCAS following surgery. This and our literature
      review highlight a need for guidelines regarding study design and methodology
      when attempting to evaluate neurosurgical cases with regard to the potential
      CCAS.

PMID- 24881641
TI  - Complexity versus the technical fix or how to put sexuality back into sexual
      health.
AB  - These reflections consider the failure of the public health establishment to
      invest in evaluations of interventions that support community groups to shift
      individual and community behaviours in favour of sexual well-being, sexual rights
      and sexual satisfaction. This article queries the willingness to invest
      substantially in researching technical interventions without simultaneously
      assessing their potential unintended consequences for sexual health well-being;
      the associated lack of will to invest in social research is also queried. The
      paper proposes that part of the challenge is the research paradigm that fears
      complexity, despite growing recognition that sexuality and sexual health are
      products of a complex intersection of factors, and they require research and
      evaluation methodologies that recognise such complexity. The paper argues that
      given the wide-ranging efforts to promote shifts in community norms and practices
      in relation to sexuality, an opportunity is being lost due to the failure to use
      ongoing process and outcome evaluations to inform interventions that would
      provide implementers and groups in communities with resources and ideas to
      strengthen the quality of their efforts in different contexts, thereby failing to
      meet the promise of the International Conference on Population and Development. 

PMID- 24881642
TI  - Does the level of amniotic fluid have an effect on the accuracy of sonographic
      estimated fetal weight at term?
AB  - OBJECTIVE: Controversy exists concerning the impact of amniotic fluid index (AFI)
      on the accuracy of sonographic estimation of fetal weight (EFW). Thus, we aimed
      to evaluate whether differences in AFI has an influence on the accuracy of
      sonographic EFW. METHODS: All term, singleton pregnancies which underwent a
      sonographic EFW and measurement of AFI within a week from delivery were included.
      Cases were stratified into three categories according to AFI: (1) Normal AFI (51
      249 mm), (2) Oligohydramnios (AFI <= 50 mm) and (3) Polyhydramnios (AFI >= 250
      mm). Inaccurate EFW was defined if there was more than 15% difference between
      sonographic EFW and actual birthweight. RESULTS: Overall, 1746 pregnancies were
      identified (1096 with normal AFI, 455 with oligohydramnios and 195 with
      polyhydramnios). Mean AFI was 115.8 +/- 60 mm, 28.1 +/- 13 mm and 293 +/- 35 mm,
      p < 0.001, and mean sonographic EFW was 3182.5 +/- 573 g, 3118.8 +/- 517 g and
      3713.2 +/- 461 g, p < 0.001, respectively. Demographic data and gestational age
      at delivery were similar. Mean birthweight was 3221.7 +/- 535 g, 3132.5 +/- 505 g
      and 3654.1 +/- 480 g, p < 0.001, respectively. The rate of inaccurate EFW was
      similar between the groups (8.4%, 8.7% and 9.7%, p = 0.19, respectively). On
      multivariate analysis, AFI was not associated with EFW inaccuracy (OR 1.01, 95%
      C.I 0.67-1.54, p = 0.93). CONCLUSION: AFI has limited impact on the percentage of
      errors in sonographic fetal weight estimation a week prior delivery.

PMID- 24881643
TI  - Auditory brainstem implants (ABIs)--20 years of clinical experience in Uppsala,
      Sweden.
AB  - CONCLUSIONS: Even though sound perception may be limited after treatment with an
      auditory brainstem implant (ABI), it provides benefits and should be selectively
      offered to patients. Importantly the patients must be motivated, given reasonable
      expectations of outcome and offered long-term rehabilitation with a considerable
      'learn to listen' period with the implant device. OBJECTIVES: To describe the
      clinical experiences and results of 24 ABI surgeries performed in Uppsala
      University Hospital between 1993 and 2013. METHODS: Most patients (n = 20)
      suffered from neurofibromatosis type 2 (NF2); a few patients (n = 4) were
      paediatric non-NF2 patients. The files were searched for information on the
      presurgery size of the vestibular schwannoma, whether the patient had undergone
      gamma knife treatment, the surgical approach, the side effects of the surgery and
      of the use of the implant, the electrode activation pattern and implant use, and
      categories of auditory performance (CAP) score. RESULTS: Our results show that
      many patients greatly benefited from an ABI, and most of the patients used their
      implants even though the hearing improvements usually consisted of awareness of
      surrounding sounds and improved lip-reading. No severe side effects were observed
      from implant stimulation.

PMID- 24881649
TI  - Persistently retained interferon-gamma responsiveness in individuals with a
      history of pulmonary tuberculosis.
AB  - The interferon gamma (IFN-gamma) release assays (IGRAs) are the best method of
      detecting Mycobacterium tuberculosis infection. However, reports on IGRAs results
      obtained during and right after the treatment of tuberculosis (TB) have presented
      differing results. Some studies have shown declining responses, whereas other
      reports described persistent, fluctuating, or increasing responses. We postulated
      that the IGRA-positivity will decrease or revert long time after treatment of TB,
      and thus, evaluated the response of IGRA in subjects with a history of pulmonary
      TB. Seventy subjects (M:F = 51:19; age = 53.2 +/- 11.8 years) underwent
      tuberculin skin tests (TSTs) and IGRA. The interval of time elapsed after the
      completion of anti-TB treatment was < 10 years for 16 subjects, 10-20 years for
      13 subjects, 20-30 years for 16 subjects, and >= 30 years for 25 subjects. The
      TST was positive in 49 subjects (74%) and negative in 17 subjects (26%). The IGRA
      was positive in 52 subjects (74%) and negative in 18 subjects (26%). The IFN
      gamma level and the size of induration showed good correlation (r = 0.525, P <
      0.001). However, the correlation between time elapsed after the completion of
      anti-TB treatment and the size of induration or that between time and the IFN
      gamma level was not significant. The TST and IGRA were positive in 72.7% and
      68.0% of subjects >= 30 years after the treatment of pulmonary TB. In conclusion,
      majority of subjects with a history of pulmonary TB are IGRA-positive, even a few
      decades after the completion of anti-TB treatment. 

PMID- 24881644
TI  - Does stress induce bowel dysfunction?
AB  - Psychological stress is known to induce somatic symptoms. Classically, many gut
      physiological responses to stress are mediated by the hypothalamus-pituitary
      adrenal axis. There is, however, a growing body of evidence of stress-induced
      corticotrophin-releasing factor (CRF) release causing bowel dysfunction through
      multiple pathways, either through the HPA axis, the autonomic nervous systems, or
      directly on the bowel itself. In addition, recent findings of CRF influencing the
      composition of gut microbiota lend support for the use of probiotics,
      antibiotics, and other microbiota-altering agents as potential therapeutic
      measures in stress-induced bowel dysfunction. 

PMID- 24881650
TI  - Pathological and immunohistochemical findings of natural highly pathogenic avian
      influenza infection in tufted ducks during 2010-2011 outbreaks in Japan.
AB  - In the winter of 2010-2011, an outbreak of highly pathogenic avian influenza
      virus (HPAIV) infection occurred in wild and domestic birds in Japan. Tufted
      ducks were found dead in an urban area of Toyota City, Koriyama, Fukushima
      Prefecture. Two tufted ducks were examined histopathologically,
      immunohistochemically and molecularly. Gross findings included marked dark-red
      clotted blood in the pectoral muscles and multifocal hemorrhages on the serous
      membranes. Microscopically, non-suppurative meningoencephalitis, multifocal to
      coalescing pancreatic necrosis and severe pulmonary congestion were observed.
      HPAIV antigen was detected in the malacic areas, neuronal, glial and ependymal
      cells, pulmonary capillary endothelial cells and epithelium of pulmonary
      bronchioles, necrotic pancreatic acini and degenerated cardiac myocytes. The
      HPAIV isolate was genetically classified into clade 2.3.2.1 group A. The broad
      distribution of virus antigen in brain and pulmonary tissues associated with
      HPAIV spontaneous infection in tufted ducks might be useful in understanding its
      pathogenesis in nature. 

PMID- 24881651
TI  - Regulation of epithelial cell tight junctions by protease-activated receptor 2.
AB  - A layer of epithelial cells prevents the invasion of bacteria and the entry of
      foreign substances into the underlying tissue. The disruption of epithelial tight
      junctions initiates and exacerbates inflammation. However, the precise mechanism
      underlying the disruption of the epithelial tight junction remains unclear. The
      activation of protease-activated receptor 2 (PAR2) by serine proteases produced
      by some bacteria and mast cells contributes to inflammation in many tissues. In
      the present study, we tested the hypothesis that PAR2 activation affects the
      structure and function of tight junctions in Madin-Darby canine kidney (MDCK)
      cells. Although the application of a PAR2-activating peptide, PAR2-AP, from the
      apical side of MDCK cells failed to modify the transepithelial resistance (TER),
      its application from the basal side markedly suppressed the TER. In 3-dimensional
      cultures of MDCK cells expressing the mCherry-tagged PAR2, a lateral localization
      of PAR2 was observed. The application of PAR2-AP from the basal side changed the
      localization of the tight junctional protein, zonula occludin-1. Furthermore,
      PAR2-AP induced the phosphorylation of p38 MAP kinase. A p38 MAP kinase
      inhibitor, SB202190, inhibited PAR2-AP-induced changes in TER. Our results
      suggest that the activation of PAR2 leads to the disruption of tight junctions
      and increases the barrier permeability through the activation of p38 MAPK, which
      may cause the initiation and exacerbation of inflammation. 

PMID- 24881652
TI  - Accumulation of eosinophils in the infundibulum of the bovine oviduct just after
      ovulation.
AB  - This study was to investigate the localization and distribution of eosinophils
      (EOS) in the bovine oviduct throughout the estrous cycle. Histological studies
      revealed more abundant EOS in the infundibula of the oviducts ipsilateral to the
      preovulatory dominant follicle and the ovulated ovary. The number of EOS was
      higher in the infundibula of the oviducts ipsilateral to the ovulated ovary than
      those of the oviducts contralateral to the ovulated ovary. The infundibula of the
      oviducts ipsilateral to the preovulatory dominant follicle had higher number of
      EOS than those of the oviducts ipsilateral to the mid-cycle corpus luteum. The
      number of EOS in the isthmus, but not in the ampulla, was higher in the outer
      layers (tunica muscularis and tunica serosa) than in the inner layers (tunica
      mucosa and tunica submucosa) during the estrous cycle. Thus, the EOS number
      varied with the region of the bovine oviduct, with greater number in the
      infundibula of the oviduct ipsilateral to the ovulated ovary, suggesting the
      impact of ovulation. 

PMID- 24881654
TI  - High-frequency acoustic for nanostructure wetting characterization.
AB  - Nanostructure wetting is a key problem when developing superhydrophobic surfaces.
      Conventional methods do not allow us to draw conclusions about the partial or
      complete wetting of structures on the nanoscale. Moreover, advanced techniques
      are not always compatible with an in situ, real time, multiscale (from macro to
      nanoscale) characterization. A high-frequency (1 GHz) acoustic method is used for
      the first time to characterize locally partial wetting and the wetting transition
      between nanostructures according to the surface tension of liquids (the variation
      is obtained by ethanol concentration modification). We can see that this method
      is extremely sensitive both to the level of liquid imbibition and to the
      impalement dynamic. We thus demonstrate the possibility to evaluate the critical
      surface tension of a liquid for which total wetting occurs according to the
      aspect ratio of the nanostructures. We also manage to identify intermediate
      states according to the height of the nanotexturation. Finally, our measurements
      revealed that the drop impalement depending on the surface tension of the liquid
      also depends on the aspect ratio of the nanostructures. We do believe that our
      method may lead to new insights into nanoscale wetting characterization by
      accessing the dynamic mapping of the liquid imbibition under the droplet. 

PMID- 24881653
TI  - Corneal-protective effects of an artificial tear containing sodium hyaluronate
      and castor oil on a porcine short-term dry eye model.
AB  - The corneal-protective effects of an artificial tear containing sodium
      hyaluronate (SH) and castor oil (CO) were evaluated on a porcine short-term dry
      eye model. Fresh porcine eyes with an intact cornea were treated with an
      artificial tear of saline, SH solution (0.1%, 0.5% or 1%), CO solution (0.5%, 1%
      or 5%) or a mixture solution containing 0.5% SH and 1% CO and then desiccated for
      60, 90 or 180 min. To assess corneal damage, the eyes were stained with methylene
      blue (MB) or lissamine green (LG). The staining score of MB, absorbance of MB
      extracted from the cornea and staining density of LG increased significantly with
      increasing desiccation time in untreated and all artificial tear-treated eyes,
      although there were no significant differences in staining scores and absorbance
      of MB between eyes treated continuously with saline and 1% SH-treated ones at 60
      and 90 min of desiccation or the mixture-treated eyes at 60 min of desiccation.
      No significant differences in the staining density of LG were also found between
      continuous saline-treated eyes and ones desiccated for 60 min and treated with 1%
      SH and the mixture. Mild cytoplasmic vacuolations were histopathologically
      observed in the basal and wing cells in eyes desiccated for 60 min and treated
      with 1% SH and the mixture. The mixture solution containing 0.5% SH and 1% CO has
      protective effects against corneal desiccation similar to those of 1% SH and
      would be helpful as an artificial tear. 

PMID- 24881655
TI  - An evaluation of acute hydrogen sulfide poisoning in rats through serum
      metabolomics based on gas chromatography-mass spectrometry.
AB  - Hydrogen sulfide (H2S) is the second leading cause of toxin-related deaths in the
      operational site. Its main target organs of toxic effects are the central nervous
      system and respiratory system. In this study, we developed a serum metabonomic
      method, based on gas chromatography-mass spectrometry (GC/MS), to evaluate the
      effect of acute poisoning by hydrogen sulfide on rats. Pattern recognition
      analysis, including both principal component analysis (PCA) and partial least
      squares-discriminate analysis (PLS-DA), revealed that acute hydrogen sulfide
      poisoning induced metabolic perturbations. Compared to the control group, the
      level of urea, glucose, glyceryl stearate in rat serum of the poisoning group
      increased after two hours, and the level of glucose, docosahexaenoic acid,
      glyceryl stearate and arachidonic acid in rat serum of the poisoning group
      increased after 48 h, while the L-valine, galactose, L-tyrosine levels decreased.
      Our results indicate that metabonomic methods based on GC/MS may be useful to
      elucidate acute hydrogen sulfide poisoning through the exploration of biomarkers.

PMID- 24881657
TI  - Synthesis and preliminary biologic activity evaluation of nitric oxide-releasing
      andrographolide derivatives in RIN-m cells.
AB  - Pancreatic beta-cell dysfunction and death are important feature of diabetes
      mellitus. Beta-cell protection has demonstrated clinical benefits in the
      treatment of this disease. In the present study, andrographolide derivatives with
      nitric oxide (NO)-releasing capability were synthesized and their protective
      effects against tert-butyl hydroperoxide (t-BHP) induced cell damage were
      investigated in RIN-m cells. Compound 6b was found to release a moderate amount
      of NO and was more potent than its natural parent andrographolide in inhibiting
      cell apoptosis. These findings suggested that andrographolide derivatives with NO
      releasing capacity may be a potential therapy for diabetes. 

PMID- 24881656
TI  - Synthesis and biological evaluation of 2-substituted quinoline 6-carboxamides as
      potential mGluR1 antagonists for the treatment of neuropathic pain.
AB  - A series of 2-amino and 2-methoxy quinoline-6-carboxamide derivatives have been
      synthesized and their metabotropic glutamate receptor type 1 (mGluR1)
      antagonistic activities were evaluated in a functional cell-based assay. The
      compound 13c showed the highest potency with IC50 value of 2.16 uM against
      mGluR1. Finally, in vivo evaluation of 13c in the rat spinal nerve ligation (SNL)
      model exhibited weak analgesic effects with regard to both mechanical allodynia
      and cold allodynia.

PMID- 24881658
TI  - Isoquinoline derivatives as potent, selective, and orally active CRTH2
      antagonists.
AB  - Synthesis and structure-activity relationship of a novel series of isoquinoline
      CRTH2 antagonists bearing a methylene linker between the isoquinoline and
      benzamide moieties were described. Optimization focusing on the substituents of
      the benzamide portion in the right hand part of the molecule led to the
      identification of TASP0412098 (9l), which is a potent, selective CRTH2 antagonist
      (binding affinity: IC50=2.1 nM, functional activity: IC50=12 nM). Compound 9l,
      which was orally bioavailable in mice and guinea pigs, showed in vivo efficacy
      after oral administration in a bronchial asthma model of guinea pigs.

PMID- 24881659
TI  - Characterization of a doxorubicin liposome formulation by a novel in vitro
      release test methodology using column-switching high-performance liquid
      chromatography.
AB  - A novel in vitro release test methodology for a liposome formulation was
      developed using a column-switching high-performance liquid chromatography (HPLC)
      system. Doxorubicin (DXR) liposome formulations were used as a model. A DXR
      liposome formulation was dispersed into a release medium, and the dispersion
      fluid was directly injected at predetermined time points into the column
      switching HPLC system. To evaluate the release profile, this system can be used
      for determining the released and encapsulated DXR in the liposome formulation
      separately. Comparison with a conventional in vitro release test methodology by
      dialysis revealed that the methodology developed by column-switching HPLC had no
      rate-limiting process of membrane permeation of the drug (which is occasionally
      observed in the dialysis method). The in vitro release profiles of DXR liposome
      formulations were well characterized using the method developed by column
      switching HPLC, and different in vitro release characteristics were revealed. The
      developed method did not require a large amount of sample or a complicated
      pretreatment. In addition, the developed column-switching HPLC system was
      applicable for characterization of the encapsulation profile of liposome
      formulations. 

PMID- 24881660
TI  - Preparation and evaluation of solid dispersion of atorvastatin calcium with
      Soluplus(r) by spray drying technique.
AB  - The aim of the present study was to investigate the effect of Soluplus(r) on the
      solubility of atorvastatin calcium and to develop a solid dispersion formulation
      that can improve the oral bioavailability of atorvastatin calcium. We
      demonstrated that Soluplus(r) increases the aqueous solubility of atorvastatin
      calcium. Several solid dispersion formulations of atorvastatin calcium with
      Soluplus(r) were prepared at various drug : carrier ratios by spray drying.
      Physicochemical analysis demonstrated that atorvastatin calcium is amorphous in
      each solid dispersion, and the 2 : 8 drug : carrier ratio provided the highest
      degree of sustained atorvastatin supersaturation. Pharmacokinetic analysis in
      rats revealed that the 2 : 8 dispersion significantly improved the oral
      bioavailability of atorvastatin. This study demonstrates that spray-dried
      Soluplus(r) solid dispersions can be an effective method for achieving higher
      atorvastatin plasma levels. 

PMID- 24881661
TI  - Properties of precipitate of creaming down by (-)-epigallocatechin-3-O-gallate
      and caffeine.
AB  - An aqueous solution of equimolecular amounts of gallated catechin (-)
      epigallocatechin-3-O-gallate (EGCg) and caffeine afforded a crude precipitate by
      creaming, which crystallized slowly for about three months at 10 degrees C to
      give a colorless block crystal. The crystal was determined to be a 2 : 2 complex
      of EGCg and caffeine by X-ray crystallographic analysis. The 2 : 2 complex was
      formed with the cooperative effect of three intermolecular interactions, pi-pi
      and CH-pi interactions, and intermolecular hydrogen bonds. Upon formation of the
      2 : 2 complex, a caffeine molecule was captured by a hydrophobic space formed by
      the aromatic rings A, B, and B' rings of two EGCg molecules. Judging from the
      entropy value, the shift value in the chemical shift of proton signals in (1)H
      NMR spectra, the NT1 value, and nuclear Overhauser effects (NOEs), it was thought
      that the structure of complexes of EGCg and caffeine in aqueous solution were the
      same as their crystal structure. 

PMID- 24881662
TI  - Usefulness of pressure-sensitive adhesives as a pretreatment material before
      application of topical drug formulations and a peeling tape for excess stratum
      corneum layers.
AB  - Two unique pressure-sensitive adhesive (PSA) tapes (PSA-A, -B) with different
      adhesive properties of commercial PSAs were prepared and evaluated for their
      usefulness as a pretreatment material prior to the application of transdermal
      therapeutic systems or topical drug formulations and also as a peeling agent
      against excess layers of the stratum corneum. In the present study, in vitro
      permeation experiments were conducted using vertical type diffusion cells and
      excised hairless rat or porcine skin from which the stratum corneum had been
      stripped several times with PSAs. The results obtained revealed that PSA-A and -B
      had higher stripping or peeling effects than those of the marketed PSAs. Marked
      changes were observed in skin barrier function before and after stripping using
      PSAs, and the enhancement effect on the skin permeation of drugs achieved by
      stripping the stratum corneum was markedly different between the PSAs. PSA-A, in
      particular, markedly improved skin permeation and the skin concentration of
      topically applied chemical compounds because it removed many layers of the
      stratum corneum when skin was stripped only a few times. In contrast, when PSA-B
      was used to pretreat the skin surface, the extent of skin permeation and
      concentration of drugs was safely increased because only a few layers of the
      stratum corneum were removed, even with repeated stripping. The enhancement
      effect achieved by PSA-B was not as high as that by PSA-A. Thus, stripping with
      PSA-A can be used as a penetration enhancement tool, whereas PSA-B can be used as
      a peeling material against excess layers of the stratum corneum. 

PMID- 24881664
TI  - Analysis of the pretreatment effect of ethanol on the stratum corneum- and hair
      follicular-penetration of drugs using the hair follicle-plugging method.
AB  - The hair follicle-plugging method was used to analyze the effects of EtOH on skin
      permeation pathways. METHODS: In vitro permeation experiments were performed on 4
      model drugs [isosorbide mononitrate (ISMN), ionized lidocaine (ionized LC),
      fluorescein (FL), and fluorescein isothiocyanate (FITC)-dextran 4 kDa (FD-4)]
      using excised pig ear skin. The skin permeations of ionized LC, FL, and FD-4 were
      decreased by hair follicle-plugging. Hair follicle-plugging prevented the skin
      permeation of FL and FD-4 in EtOH-pretreated skin, but did not prevent that of
      ISMN. On the other hand, the effect of hair follicle-plugging on the permeation
      of ionized LC was different among the pretreatment conditions. These results
      indicate that the EtOH pretreatment greatly affected the aqueous pathway in the
      stratum corneum and hair follicles.

PMID- 24881663
TI  - A cluster analysis on the structural diversity of protein crystals, exemplified
      by human immunodeficiency virus type 1 protease.
AB  - Information on many protein crystal structures has recently become available due
      to developments in crystallographic techniques. Even for a single kind of
      protein, several and sometimes many crystal structures are available. Human
      immunodeficiency virus type 1 (HIV-1) protease is one of the most extensively
      studied viral proteins, and about six hundred crystal structures have been
      determined. In this work, we examined the structural diversity of HIV-1 protease,
      classifying crystal structures into several groups from the viewpoint of
      similarity in atom geometry. Using 499 crystal structures downloaded from the
      Protein Data Bank (PDB), cluster analysis was applied to the whole body of HIV-1
      protease and also to a limited number of residues at the binding pocket. As a
      consequence of clustering with regard to the whole body, 499 crystal structures
      were separated into 6 groups. It was found that a major factor for this
      separation is the space group of the crystals and that the space group strongly
      depends on the agents used in the protein crystallization. Amino acid mutation is
      a minor factor for separation in clustering. In cluster analysis for a limited
      number of residues at the binding pocket, crystal structures were not distinctly
      separated, and no clear factor linked to the separation was clarified. The
      results suggest that amino acid mutations have little effect on the coordinates
      of the main-chain atoms of HIV-1 protease. Hence, the changes in drug efficacy or
      substrate fitness caused by mutations are mainly due to the physicochemical
      features of amino acid side chains. 

PMID- 24881665
TI  - Salusin-beta, an antimicrobially active peptide against Gram-positive bacteria.
AB  - Salusin-beta has been detected in numerous mammalian tissues and has been shown
      to have various effects on the cardiovascular system. In this study, we showed
      that salusin-beta exhibited potent antibacterial activity against Gram-positive
      microorganisms such as Bacillus subtilis NBRC 3513, Bacillus megaterium ATCC
      19213, Staphylococcus aureus NBRC 12732, and Staphylococcus epidermidis NBRC
      12933. A cytoplasmic membrane-depolarizing assay using the DiSC3(5) dye revealed
      that the addition of 4 nmol/mL of salusin-beta caused the leakage of fluorescence
      dye from Staphylococcus aureus NBRC 12732. The antimicrobial potency and circular
      dichroism (CD) spectroscopy of five analogs related to salusin-beta were examined
      to determine structure-function relationships in its N- and C-terminal regions.
      The results obtained suggest that the N-terminal sequences of the salusin-beta
      molecule are important for the expression of the potent antimicrobial activity of
      this peptide. A profile corresponding to that of the alpha-helix conformation was
      observed in the salusin-beta solution. 

PMID- 24881666
TI  - Synthesis and biological activity of Schiff base series of valproyl, N-valproyl
      glycinyl, and N-valproyl-4-aminobenzoyl hydrazide derivatives.
AB  - Series of Schiff bases of valproic acid hydrazide, N-valproylglycine hydrazide
      and N-valproyl-4-aminobenzoyl hydrazide derivatives were synthesized and
      characterized by IR, NMR ((1)H- and (13)C-NMR) and elemental analysis. The
      prepared compounds were evaluated in transgenic zebrafish embryos (Tg: flil-1:
      enhanced green fluorescent protein (EGFP)) for antiangiogenic activity and in
      HepG2 liver carcinoma cell line for anti cancer activity. The Schiff bases of N
      valproylglycine hydrazide derivatives were most potent in term of suppressing
      angiogenic blood vessels formation and anticancer activity at very low
      concentration, followed by the Schiff bases of valproic acid hydrazide
      derivatives which exhibited moderate activity, while the Schiff bases of N
      valproyl-4-aminobenzoyl hydrazide derivatives, ethyl 4-(2
      propylpentanamido)benzoate (VABE) and N-(4-(hydrazinecarbonyl)phenyl)-2
      propylpentanamide (VABH) in contrast exhibited pro-angiogenic activity and weaker
      anticancer activity which mean that these derivatives targeted a common signaling
      pathway in term of affecting the blood vessels formation. 

PMID- 24881667
TI  - cis-Cinnamic acid selective suppressors distinct from auxin inhibitors.
AB  - The activity of cis-cinnamic acid (cis-CA), one of the allelochemicals, in plants
      is very similar to that of indole-3-acetic acid (IAA), a natural auxin, and thus
      cis-CA has long been believed to be an analog of auxin. We have reported some
      structure-activity relationships studies by synthesizing over 250 cis-CA
      derivatives and estimating their inhibitory activities on root growth inhibition
      in lettuce. In this study, the compounds that showed low- or no-activity on root
      growth inhibition were recruited as candidates suppressors against cis-CA and/or
      auxin and tested for their activity. In the presence of cis-CA, lettuce root
      growth was inhibited; however, the addition of some cis-CA derivatives restored
      control-level root growth. Four compounds, (Z)-3-(4-isopropylphenyl)acrylic acid,
      (Z)-3-(3-butoxyphenyl)acrylic acid, (Z)-3-[3-(pentyloxy)phenyl]acrylic acid, and
      (Z)-3-(naphthalen-1-yl)acrylic acid were selected as candidates for a cis-CA
      selective suppressor they allowed the recovery of root growth from inhibition by
      cis-CA treatment without any effects on the IAA-induced effect or elongating
      activity by themselves. Three candidates significantly ameliorated the root
      shortening by the potent inhibitor derived from cis-CA. In brief, we have found
      some cis-CA selective suppressors which have never been reported from inactive
      cis-CA derivatives for root growth inhibition. cis-CA selective suppressors will
      play an important role in elucidating the mechanism of plant growth regulation. 

PMID- 24881668
TI  - Ferric human neuroglobin scavenges superoxide to form oxy adduct.
AB  - Neuroglobin (Ngb) is the third member of the vertebrate globin family, and the
      structure was solved as a typical globin fold with a b-type heme. Although it has
      been proposed that Ngb could be involved in neuroprotection against oxidative
      stress, the protective mechanism has not been fully identified yet. In order to
      clarify functions under hypoxic condition, in this study, we focused on the
      scavenger activity of human Ngb (hNgb) against superoxide. The activity of hNgb
      for superoxide was evaluated to be 7.4 uM for IC50, the half maximal inhibitory
      concentration. The result indicates that hNgb can be an anti-oxidant, and the
      value was almost the same as that of ascorbic acid. In addition, we characterized
      oxidation states of a heme iron in superoxide-treated hNgb with spectroscopic
      measurements. Superoxide-treated hNgb in the ferric form was readily converted to
      the oxygenated ferrous form, and the result suggested that ferric hNgb could
      scavenge superoxide by change of an oxidation state in a heme iron. Moreover,
      mutational experiments were performed, and the each variant mutated at 46 and 55
      positions suggested a disulfide bond between Cys46 and Cys55 could be essential
      to be sensors for oxidative stress with the direct binding of superoxide. As a
      consequence, we concluded that redox changes of the heme iron and the disulfide
      bond could regulate neuroprotective functions of hNgb, and it suggests that hNgb
      can afford protection against hypoxic and ischemic stress in the brain.

PMID- 24881669
TI  - Physical and sensory characterizations of oral coatings of oil/water emulsions.
AB  - The physical and sensory properties of oil coatings on the tongue formed by five
      oil/water emulsions varying in oil content were investigated. A total of 20
      subjects processed orally each emulsion for 30 s in triplicate. In vivo
      fluorescence measurements at the front and back of the anterior tongue were made
      to quantify the oil fraction deposited at different time points. Calibration
      lines relating fluorescence intensity to oil fraction were determined using pig
      tongues at 37.5  degrees C to mimic oral conditions. The oil fraction on the
      tongue increased linearly with an increasing oil content of the emulsions. The
      oil fraction deposited at the back of the anterior tongue was 1.5-2.0* larger
      than at the front. The intensity of sensory attributes describing after-feel
      perception was related to the oil fraction by Weber-Fechner's law. This study
      uses in vivo fluorescence to study food behavior in the mouth and unravel new
      insights in after-feel perception of emulsions. 

PMID- 24881671
TI  - Layer-by-layer self-assembly of TiO2 hierarchical nanosheets with exposed {001}
      facets as an effective bifunctional layer for dye-sensitized solar cells.
AB  - Layer-by-layer self-assembled TiO2 hierarchical nanosheets with exposed {001}
      facets have been successfully fabricated via a simple one-step solvothermal
      reaction. The anatase TiO2 layer-by-layer hierarchical nanosheets (TiO2 LHNs)
      exhibit favorable light scattering effect and large surface area, owing to their
      layer-by-layer hierarchical structure. When applied to the dye-sensitized solar
      cells (DSSCs), the layer-by-layer hierarchical structure with exposed {001} facet
      could effectively enhance light harvesting and dye adsorption, followed by
      increasing the photocurrent of DSSCs. As a result, the photoelectric conversion
      efficiency (eta) of 7.70% has been achieved for the DSSCs using TiO2 LHNs as the
      bifunctional layer, indicating 21% improvement compared to the pure Degussa P25
      (6.37%) as photoanode. Such enhancement can be mainly ascribed to the better
      light scattering capability of TiO2 LHNs, higher dye adsorption on TiO2 LHN {001}
      facets, and longer lifetime of the injected electrons in TiO2 LHNs compared to
      P25, which are examined by UV-vis spectrophotometry and electrochemical impedance
      spectroscopy under the same conditions. These remarkable properties of TiO2 LHNs
      make it a promising candidate as a bifunctional scattering material for DSSCs. 

PMID- 24881670
TI  - GlyQ-IQ: glycomics quintavariate-informed quantification with high-performance
      computing and GlycoGrid 4D visualization.
AB  - Glycomics quintavariate-informed quantification (GlyQ-IQ) is a biologically
      guided glycomics analysis tool for identifying N-glycans in liquid chromatography
      mass spectrometry (LC-MS) data. Glycomics LC-MS data sets have convoluted
      extracted ion chromatograms that are challenging to deconvolve with existing
      software tools. LC deconvolution into constituent pieces is critical in glycomics
      data sets because chromatographic peaks correspond to different intact glycan
      structural isomers. The biological targeted analysis approach offers several key
      advantages to traditional LC-MS data processing. A priori glycan information
      about the individual target's elemental composition allows for improved
      sensitivity by utilizing the exact isotope profile information to focus
      chromatogram generation and LC peak fitting on the isotopic species having the
      highest intensity. Glycan target annotation utilizes glycan family relationships
      and in source fragmentation in addition to high specificity feature LC-MS
      detection to improve the specificity of the analysis. The GlyQ-IQ software was
      developed in this work and evaluated in the context of profiling the N-glycan
      compositions from human serum LC-MS data sets. A case study is presented to
      demonstrate how GlyQ-IQ identifies and removes confounding chromatographic peaks
      from high mannose glycan isomers from human blood serum. In addition, GlyQ-IQ was
      used to generate a broad human serum N-glycan profile from a high resolution
      nanoelectrospray-liquid chromatography-tandem mass spectrometry (nESI-LC-MS/MS)
      data set. A total of 156 glycan compositions and 640 glycan isomers were detected
      from a single sample. Over 99% of the GlyQ-IQ glycan-feature assignments passed
      manual validation and are backed with high-resolution mass spectra. 

PMID- 24881672
TI  - Ensemble-based docking using biased molecular dynamics.
AB  - Proteins are dynamic molecules, and understanding their movements, especially as
      they relate to molecular recognition and protein-ligand interactions, poses a
      significant challenge to structure-based drug discovery. In most instances,
      protein flexibility is underrepresented in computer-aided drug design due to
      uncertainties on how it should be accurately modeled as well as the computational
      cost associated with attempting to incorporate flexibility in the calculations.
      One approach that aims to address these issues is ensemble-based docking. With
      this technique, ligands are docked to an ensemble of rigid protein conformations.
      Molecular dynamics (MD) simulations can be used to generate the ensemble of
      protein conformations for the subsequent docking. Here we present a novel
      approach that uses biased-MD simulations to generate the docking ensemble. The MD
      simulations are biased toward an initial protein-ligand X-ray complex structure.
      The biasing maintains some of the original crystallographic pocket-ligand
      information and thereby enhances sampling of the more relevant conformational
      space of the protein. Resulting trajectories are clustered to select a
      representative set of protein conformations, and ligands are docked to that
      reduced set of conformations. Cross-docking to this ensemble and then selecting
      the lowest scoring pose enables reliable identification of the correct binding
      mode. Various levels of biasing are investigated, and the method is validated for
      cyclin-dependent kinase 2 and factor Xa. 

PMID- 24881673
TI  - Human herpesvirus types 6 and 7 infection in pediatric hematopoietic stem cell
      transplant recipients.
AB  - BACKGROUND: The immunosuppressed state in patients undergoing hematopoietic stem
      cell transplantation (HSCT) predisposes them to activation of latent viral
      infections such as herpesvirus types 6 and 7 (HHV6 and HHV7). We aimed to
      evaluate the incidence, manifestations, outcomes, and risk factors of HHV 6 and
      HHV 7 infections after pediatric hematopoietic stem cell transplantation.
      MATERIAL AND METHODS: We performed 106 HSCTs (86 allogeneic and 20 autologous) on
      94 children (56 boys, median age 7.1 years) during 2006-2012. Patients suspected
      to have HHV6 or HHV7 infections were tested using polymerase chain reaction on
      serum and/or cerebrospinal fluid. RESULTS: Among the 63 patients tested for HHV,
      10 patients (15.9%) were infected (HHV-6 (n=6), HHV-7 (n=4)) at a median of 18
      days post-HSCT (cumulative incidence 11.5% at 1 year). Manifestations included
      fever (90%), rash (70%), hepatitis (80%), pneumonitis (50%), central nervous
      system (CNS) manifestations (40%), and graft failure (10%). One patient had
      persistent CNS infection despite treatment with foscarnet, ganciclovir, and
      cidofovir. Seven patients cleared herpesvirus after a median of 22 days. Four
      patients died (relapse of malignancy [n=3], acute graft-versus-host disease
      [aGVHD] [n=1]). Herpesvirus infections were associated with adenovirus infection
      (p=0.001) and severe (grade III-IV) aGVHD (p=0.037). CONCLUSIONS: We concluded
      that HHV6 and HHV7 infections are common after pediatric HSCT. Most infections
      were self-limited and could be associated with adenovirus infection and severe
      aGVHD. Further studies are needed to evaluate predictors of severe morbidity or
      mortality, and define optimal prophylaxis and treatment.

PMID- 24881674
TI  - Palladium mediated intramolecular multiple C-X/C-H cross coupling and C-H
      activation: synthesis of carbazole alkaloids calothrixin B and murrayaquinone A.
AB  - Straightforward palladium mediated syntheses of calothrixin B and murrayaquinone
      A are described. Regioselective palladium mediated intramolecular multiple C-X/C
      H cross coupling reaction on N-(4-((2-bromophenyl)amino)-2,5-dimethoxybenzyl)-N
      (2-iodophenyl)acetamide followed by CAN oxidation afforded calothrixin B in
      excellent yield in two steps. A linear synthesis has also been developed for
      calothrixin B. Utilizing C-H functionalization as well as palladium mediated
      intramolecular C-X/C-H cross coupling reaction, murrayaquinone A synthesis was
      achieved. Overall, these synthetic methodologies provide an expedient entry to
      these biologically active alkaloids in a short reaction sequence. 

PMID- 24881675
TI  - Synthesis, stability and reactivity of the first mononuclear nonheme oxoiron(IV)
      species with monoamido ligation: a putative reactive species generated from iron
      bleomycin.
AB  - The preparation and characterisation of an oxoiron(IV) species with monoamido
      ligation are described. Reactivity studies revealed the important role of the
      amido ligand in enhancing the ability of oxoiron(IV) complexes to promote
      hydrogen atom transfer from external alkanes.

PMID- 24881677
TI  - Diffusion induced effects on geometry of Ge nanowires.
AB  - We report diffusion induced germanium nanowire growth and its dependence on the
      Ge evaporation flux. The wires show a growth rate (dL/dt) in agreement with the
      previously reported models, but detection of anomalies in the grown wires may
      indicate the prevalence of the direct Ge impinging effect on large diameter
      wires. Additionally, we demonstrate that change in deposition flux could directly
      affect the diffusion length of the Ge adatoms on the wire sidewalls. This in turn
      modifies the geometry of the grown wires by introducing a lateral growth starting
      from the base of the wire. A detailed understanding of the deposition flux effect
      on the growth and geometry of wires will result in improved knowledge of physical
      properties of wires. 

PMID- 24881678
TI  - Molecular spintronics: a web themed issue.

PMID- 24881676
TI  - Ameliorative effects of Schizandra chinensis on osteoporosis via activation of
      estrogen receptor (ER)-alpha/-beta.
AB  - Estrogen deficiency in menopausal women is the main cause of osteoporosis.
      Phytoestrogen could be a suitable candidate for treatment of post-menopausal
      osteoporosis. Recent studies showed that S. chinensis contains several lignans,
      which may be phytoestrogen. In this study, we investigated the ameliorative
      effects of S. chinensis on post-menopausal osteoporosis. 30% ethanol extract of
      S. chinensis (SC) was administered orally for 6 weeks after 7 weeks of
      ovariectomized-induced osteoporosis. Bone mineral density was significantly
      increased following increased serum osteocalcin levels by SC treatment.
      Histological analysis showed that SC reduced the increased growth plate of the
      epiphyseal plate in femur. In addition, pores within bone marrow cells filling
      the lateral and medial epicondyle were decreased. Serum estradiol concentration
      was significantly increased in the SC-treated group. The expressions of estrogen
      receptor-alpha and -beta were increased in uterus and MCF-7 breast cancer cells
      by SC treatment. And two transcriptions of proto-oncogenes, c-fos and c-Jun, were
      suppressed by treatment of SC. From these data, we propose that S. chinensis
      attenuates post-menopausal osteoporosis with its phytoestrogenic effects. S.
      chinensis may have the potential to be used as an alternative for treatment of
      osteoporosis. 

PMID- 24881679
TI  - Cytokine immunomodulation for the treatment of infectious diseases: lessons from
      primary immunodeficiencies.
AB  - Traditionally, management of infectious diseases focuses on identification of the
      causative microbe and the use of pathogen-targeted therapy. With increasing
      antimicrobial resistance, novel approaches are required. One strategy is to
      modulate those natural host immune responses that critically mediate resistance
      to specific microbes. Clinically, this host-directed tactic could be used either
      alone or in combination with antimicrobial therapy. While conceptually
      attractive, there is potential concern that the pathways governing host
      resistance to pathogens in animal models may not extrapolate linearly to humans.
      Targeting these immune processes clinically may precipitate damaging,
      epiphenomenal responses. The field of Primary Immunodeficiencies focuses on the
      characterization of humans with inborn errors of immunity. These rare conditions
      permit the identification of those molecular and cellular processes that are
      central to human susceptibility to microbes. In efforts to compensate for
      defective host responses, this field has also provided a wealth of clinical
      experience in the effective use of cytokines to treat various active infections,
      while demonstrating their safety. In this review, we provide a historical
      perspective of the treatment of infectious diseases, evolving from a focus on the
      microbe, to an understanding of human immunity; we then outline the growing
      contribution of Primary Immunodeficiencies to the rational use of adjunctive
      cytokine immunotherapy in the management of infections. 

PMID- 24881680
TI  - Financial health and social recovery.

PMID- 24881682
TI  - Building a successful public-academic partnership to support state policy making.
AB  - This column describes a partnership between the Maryland Mental Hygiene
      Administration (MHA) and the Division of Psychiatric Services Research,
      Department of Psychiatry, University of Maryland School of Medicine, that has
      implemented several evidence-based and emerging practices, such as supported
      employment, family psychoeducation, assertive community treatment, treatment for
      co-occurring mental and substance use disorders, and services for transition-age
      youths. The public-academic partnership has also created a separate center that
      employs a variety of approaches and tools to evaluate implementation fidelity and
      the quality and outcomes of services. These data are used by the legislature and
      by the governor and his executive staff to develop new policies and improvement
      strategies and monitor priority initiatives. 

PMID- 24881683
TI  - Scaling up evidence-based behavioral health care practices in New York state.
AB  - This column describes the Center for Practice Innovations (CPI), which was
      created in 2007 by the New York State Office of Mental Health and the Department
      of Psychiatry at Columbia University. CPI uses innovative approaches to build
      stakeholder collaborations, develop and maintain practitioners' expertise, and
      build agency infrastructures that support implementing and sustaining evidence
      based practices. CPI's five core initiatives provide training in co-occurring
      mental and substance use disorders, assertive community treatment, supported
      employment and education, wellness self-management, and treatment of first
      episode psychosis. Central to CPI's activities are award-winning training
      modules, statewide learning collaboratives, and use of a learning management
      system. 

PMID- 24881684
TI  - Family history.

PMID- 24881685
TI  - Why the evidence for outpatient commitment is good enough.
AB  - After nearly three decades of studies evaluating the legal practice of
      involuntary outpatient commitment, there is yet little consensus about its
      effectiveness and only limited implementation. Debate continues over how best to
      assist adults with serious mental illnesses who are unable or unwilling to
      participate in prescribed community treatment and as a result experience repeated
      involuntary hospitalizations or involvement with the criminal justice system. The
      authors comment on the Oxford Community Treatment Order Evaluation Trial (OCTET),
      a recently conducted randomized trial of outpatient commitment, and discuss the
      limitations of the study's design for resolving the persistent question of
      whether compulsory treatment is more effective than purely voluntary treatment
      for this difficult-to-reach target population. The authors conclude that the
      search for a definitive and generalizable randomized trial of outpatient
      commitment may be a quixotic quest; the field should, rather, welcome the results
      of well-conducted, large-scale, quasi-experimental and naturalistic studies with
      rigorous multivariable statistical controls. 

PMID- 24881686
TI  - Outpatient commitment and its alternatives: questions yet to be answered.
AB  - This Open Forum reviews research findings on outpatient commitment and
      alternative approaches, such as conditional hospital release and guardianship.
      Despite the accumulating evidence in favor of these practices, many questions
      remain about their essential elements and comparative effectiveness. The authors
      describe the strengths and shortcomings in existing studies and propose a
      research strategy that would take advantage of advances in methodologies, such as
      instrumental variables and propensity weighting, to design studies with a level
      of rigor comparable to that of randomized controlled trials. The Affordable Care
      Act (ACA) introduces many opportunities and resources to improve care; studies
      should also be undertaken to investigate use of outpatient commitment and
      alternative approaches in the post-ACA health care environment. 

PMID- 24881687
TI  - Outpatient commitment reexamined: a third way.

PMID- 24881688
TI  - Timing and momentum in VA's path toward Housing First.

PMID- 24881689
TI  - Timing and momentum in VA's path toward Housing First: in reply.

PMID- 24881691
TI  - Angiogenesis in esophageal and gastric cancer: a paradigm shift in treatment.
AB  - INTRODUCTION: Esophageal and stomach cancers are leading cause of cancer death
      worldwide, killing more than 1 million people each year. In unscreened
      population, patients' symptoms will trigger diagnostic workup. Most patients are
      diagnosed with advanced stage and their disease is not amenable to surgical
      resection. The disease is aggressive in nature and mostly even those patients who
      have early stage disease will eventually succumb to recurrence after definitive
      therapy. Patients with advanced esophageal and stomach cancers have very limited
      options for target agents and conventional chemotherapy has remained the standard
      of care. AREAS COVERED: Since its discovery, antiangiogenesis continues to be the
      repeating theme of cancer therapy of the modern era. However, although successful
      in other tumor types, the data from highly anticipated antiangiogenic agents from
      both the small molecule tyrosine kinase inhibitors and monoclonal antibodies for
      esophageal and gastric cancers had been disappointing. Many attribute the lack of
      survival benefit noted in clinical trials to the failure in identifying target in
      this patient population. EXPERT OPINION: The most recent clinical studies support
      that specifically attacking vascular endothelial growth factor receptors remain
      effective in esophageal and gastric cancers. These pivotal trials may prove to
      shift the paradigm of current therapy and will likely gain approval for the drug
      of interest. At the same time, the results generate more questions to understand
      the disease biology as well as to identify those patients who will benefit the
      most from such therapy.

PMID- 24881694
TI  - Abdominal compartment syndrome: it is time....

PMID- 24881695
TI  - Intraabdominal hypertension and abdominal compartment syndrome: we have paid
      attention, now it is time to understand!

PMID- 24881693
TI  - Quality, not just quantity: lessons learned from HIV testing in Salvador, Brazil.
AB  - Studies have demonstrated that an early HIV diagnosis is a critical first step
      towards continued engagement in care. We examined HIV testing experiences in
      Salvador, Brazil, to understand how a focus on quality services can inform
      service provision more generally in the post-2015 global health agenda. Seventeen
      semi-structured interviews were conducted with HIV-positive pregnant women in
      Salvador, a large urban centre of north-east Brazil. Interviews were transcribed,
      translated and coded for analysis. Deductive codes confirmed factors identified
      in the literature review. Inductive codes highlighted new factors emerging from
      the initial coding. 'Quality' was defined according to global and national
      guidelines as HIV testing with informed and voluntary consent, counselling and
      confidentiality (3Cs). No pregnant woman experienced all elements of the 3Cs.
      Three women did not experience any informed and voluntary consent, counselling or
      confidentiality. Few women provided consent overall and none received pre-test
      counselling. Post-test counselling and confidentiality of services were more
      consistently provided. This study suggests that testing in Salvador - the third
      largest city in the country - is not of the quality called for by global and
      national guidelines, despite the fact that HIV testing is being routinely
      provided for HIV-positive pregnant women in Brazil. Going forward, additional
      clarity around the 3Cs is necessary to improve how the quality, not just the
      quantity, of HIV services is measured. 

PMID- 24881696
TI  - Historical highlights in concept and treatment of abdominal compartment syndrome.
AB  - Three types of historical events are of interest, when dealing with the topic of
      abdominal compartment syndrome. The first concerns the evolution in the
      understanding of the pathophysiologic features of a compartment syndrome in
      general. The symptoms were well described by Richard von Volkmann in the 19(th)
      century. The second consists of the experimental studies devoted to measurements
      of intra-abdominal pressure. Different devices and techniques were used, in
      particular using detection locations approachable via natural body orifices
      (bladder/uterus/rectum etc). A third point of interest has come forward after the
      empirical assessment, in particular by sir Heneage Ogilvie that open
      laparostomies were beneficial in the healing of great abdominal war wounds, or
      later, of congenital abdominal wall defects. These three different views on
      pathology and treatment of life threatening abdominal hypertension have evolved
      to a concept of abdominal compartment syndrome, that with adequate diagnostic
      measures and accurate and timely intervention can now be treated with great
      success. 

PMID- 24881697
TI  - Rational intraabdominal pressure monitoring: how to do it?
AB  - INTRODUCTION: Intraabdominal hypertension (IAH) is increasingly appreciated by
      intensivists as an important cause of organ dysfunction, even at pressure levels
      which were previously thought to be harmless. Therefore, the goal of this review
      is to describe the different methods commonly used in clinical practice for
      intraabdominal pressure (IAP) measurement, the advised methodology for each
      measurement method, and finally to give a rational approach for IAP monitoring in
      daily clinical practice. METHODS: A Medline search of the English literature was
      performed using the term "intra abdominal pressure" and "measurement". This
      resulted in 194 studies, which were then analysed based on the title and
      abstract. Only clinical studies in human subjects with IAP measurement or related
      issues as the subject of the study, were considered for inclusion in the study.
      Reviews, animal experiments and case reports were excluded, while one specific
      review on IAP measurement and 3 large animal studies (domestic swine > 40 kg)
      were included in the analysis. This left us with 19 studies, published between
      1984 and 2006: 1 specific review, 2 studies in children, 13 in adults and 3 in
      domestic swine. The references from these studies were searched for relevant
      articles that may have been missed in the primary search. These articles served
      as the basis for the recommendations below. RESULTS: Clinical data regarding the
      validation of new IAP measurement methods or the reliability of established
      measurement techniques are scarce. The transvesical route, which has been studied
      most extensively, can be used as reliable route for intermittent IAP measurement,
      as long as instillation volumes below 25mL are used. Continuous IAP and APP
      monitoring can be done via a balloon-tipped catheter placed in the stomach or
      directly intraperitoneal. CONCLUSIONS: Rational IAP monitoring should be based on
      a site specific protocol, based on known risk factors, the monitoring equipment
      available and nursing staff experience, and should be linked directly to a local
      treatment protocol.

PMID- 24881698
TI  - Continuous intra-abdominal pressure monitoring.
AB  - BACKGROUND: Intra-abdominal hypertension (IAH) and abdominal compartment syndrome
      (ACS) can develop within 12 hours of ICU admission in high-risk patients. Until
      recently the intermittent intra-abdominal pressure (IAP) measurement via the
      urinary catheter was the clinical standard. This is a relatively labour intensive
      technique and its intermittent nature could prevent timely recognition of
      significant changes in IAP. The historical continuous IAP (CIAP) measurements
      were poorly reproducible (gastric route) or invasive/impractical (direct
      measurement). The aim of this paper is to review the current evidence on CIAP
      monitoring. METHODS: A broad Medline search of the English literature was
      performed using the terms of "intra abdominal pressure" and "continuous". This
      result was analysed based on the title and abstract. Only original clinical
      studies with continuous IAP measurement were considered in this review. New
      techniques of CIAP monitoring evaluated in large animal models are discussed as
      potential future directions. RESULTS: There is a growing evidence of measuring
      (monitoring) CIAP using several techniques (gastric, direct abdominal, inferior
      vena cava, and urinary bladder. The strongest evidence supports the direct
      abdominal, the gastric and the bladder route. From these three techniques the
      CIAP monitoring via the bladder has excellent agreement with the current standard
      of intermittent bladder pressure measurement. While the direct measurement could
      be very accurate it is an invasive method and feasible in patient who underwent
      laparotomy or laparoscopy. CONCLUSIONS: Until a better technique is available the
      CIAP monitoring via the bladder or stomach should be considered as the standard
      for continuous monitoring of the IAP. It is a less labour intensive, safe, less
      invasive and reliable method.

PMID- 24881699
TI  - Noosa, 2 years later... a critical analysis of recent literature.
AB  - INTRODUCTION: Since the second World Congress on the Abdominal Compartment
      Syndrome (WCACS) in Noosa 2 years ago, interest and publications on intra
      abdominal hypertension (IAH) and ACS have increased exponentially. This paper
      aimed to critically review recent publications and put this new data into the
      context of already acquired knowledge concerning IAH/ACS. METHODS: A Medline and
      PubMed search was performed from January 2005 up to now using "intra-abdominal
      pressure (IAP)", "intra-abdominal hypertension (IAH)", "abdominal compartment
      syndrome (ACS)" and "decompressive laparotomy" as search items. RESULTS: Although
      consensus definitions of IAH/ACS have been formulated recently, data on awareness
      are still disconcerting. Several groups refined current IAP measurement
      techniques and tested new direct IAP measurement devices for use in selected
      subpopulations. A series of recent publications identified specific patient
      subpopulations in IAH/ACS, like patients with burns or severe acute pancreatitis,
      with their specific pathophysiology and therapy. Although many studies already
      assessed the effect of elevated IAP on regional and micro-circulatory organ
      perfusion, a number of new publications attempted to unravel the link between
      elevated IAP and more "downstream" organ function or histology. Finally, therapy
      for IAH/ACS still reveals more questions than it answers. Global resuscitation
      does not necessarily equate with organ resuscitation. In fact, fluid
      resuscitation may even induce IAH/ACS. CONCLUSIONS: After publication of
      consensus guidelines on IAH/ACS, there is an urgent need for human intervention
      studies and, in parallel, clinically relevant animal models. Given moderately low
      incidence of ACS and the complex and interrelated pathologies of the critically
      ill patient with IAH/ACS, large animal models of pathology-induced IAH/ACS might
      create the opportunity to gain clinically relevant knowledge on the treatment of
      IAH/ACS.

PMID- 24881700
TI  - Consensus conference definitions and recommendations on intra-abdominal
      hypertension (iah) and the abdominal compartment syndrome (acs) - the long road
      to the final publications, how did we get there?
AB  - OBJECTIVE: There has been an exponentially increasing interest in intraabdominal
      hypertension (IAH) and the abdominal compartment syndrome (ACS) over the last
      decade, and different definitions have been suggested. Nevertheless, there has
      been an impetus from experts in the field to modify these definitions to reflect
      our current understanding of the pathophysiology of these syndromes. An
      international multidisciplinary group of interested doctors met with the goal of
      agreeing on a set of definitions that could be applied to patients with IAH and
      ACS. The goal of this consensus group was to provide a conceptual and practical
      framework to further define ACS, a progressive injurious process that falls under
      the generalized term 'IAH' and that includes IAH-associated organ dysfunction.
      DESIGN: In total, 21 North American, Australasian and European surgical, trauma
      and critical care specialists agreed to standardize the current definitions for
      IAH, ACS and related conditions in preparation for the second World Congress on
      Abdominal Compartment Syndrome (WCACS). The WCACS-meeting was endorsed by the
      European Society of Intensive Care Medicine (ESICM) and the World Society on
      Abdominal Compartment Syndrome (WSACS). METHODS: The consensus conference (Noosa,
      Australia; December 7, 2004) was attended by 21 specialists from Europe,
      Australasia and North America and approximately 70 other congress participants.
      In advance of the conference, a blueprint for the various definitions was
      suggested. After the conference the participants corresponded electronically with
      feedback. A writing committee was formed at the conference and developed the
      final manuscript based on executive summary documents generated by each
      participant. The final report of the 2004 International ACS Consensus Definitions
      Conference has recently been published. This article will describe the long road
      towards this final publication with the evolution of the different definitions
      and recommendations from the initial suggestions in 2004 to the further
      refinement and final publications in 2006 and 2007. It will try to explain how we
      got there and will also give the percentage of agreement with each proposed
      definition by the participants. RESULTS: New definitions were offered for some
      terms, while others were discarded and not kept in the final manuscript.
      Different cut-offs for defining IAH and ACS were given, as well as broad
      definitions of primary, secondary and recurrent IAH/ACS. A classification system
      was introduced taking into account the duration, origin, and etiology of IAH. The
      use of an organ severity scoring method, by means of the Sequential Organ Failure
      Assessment (SOFA) score when dealing with ACS patients was not recommended as an
      adjunctive tool to assess morbidity in the final publication. CONCLUSION: This
      document reflects a process whereby a group of experts and opinion leaders
      suggested definitions for IAH and ACS. This document should be used as a
      reference for the next consensus definitions conference in March 2007.

PMID- 24881701
TI  - The secondary and recurrent abdominal compartment syndrome.
AB  - INTRODUCTION: The Secondary Abdominal Compartment Syndrome (SACS) refers to cases
      of the ACS that do not originate from the abdominopelvic region. With greater
      awareness of the physiologic consequences of raised intra-abdominal hypertension
      (IAH), cases of the SACS are being increasingly described. The prior treatment or
      the presence of a partially open abdomen does not preclude the ACS if the abdomen
      and viscera continue to swell or the clinician is not vigilant in monitoring
      intra-abdominal pressure (IAP). Such recurrent cases (RACS) have been defined as
      those which redevelop following the previous medical or surgical treatment of
      primary or SACS. Although there has been a diverse range of etiologies
      implicated, these cases seem to be linked by the common occurrence of severe
      shock requiring aggressive fluid resuscitation. The aim of this paper is to thus
      to review the historical background, awareness, definitions, pathophysiological
      implications and treatment options for SACS and RACS. METHODS: This review will
      focus on the available literature regarding SACS and RACS. A Medline and Pubmed
      search was performed using the keywords; secondary abdominal compartment syndrome
      AND secondary AND tertiary AND recurrent AND abdominal compartment syndrome AND
      intra-abdominal pressure AND intra-abdominal hypertension. Bibliographies of
      recovered papers were hand-searched for other appropriate references. The
      resulting references were included in the current review on the basis of
      relevance and scientific merit Results: There has been remarkably little specific
      study of these entities outside of specific groups such as those injured by
      thermal or traumatic injury. The epidemiology, risk factors for, treatment of and
      most importantly, strategies for prevention all remain scientifically unknown and
      therefore based on opinion. Notable, although small, studies suggest that
      specific resuscitation practices may avert these conditions. CONCLUSIONS: ACS can
      occur in any patient who is critically ill and subject to visceral and somatic
      swelling, regardless of whether the inciting pathology is extra-abdominal. The
      ACS may also reoccur with recurrent shock and swelling even if previous therapies
      had partially addressed IAH. Therefore IAP measurements should be considered a
      routine monitoring for the critically ill, especially those subjected to shock
      and requiring a subsequent resuscitation. Much further study is required to
      understand the differences in etiology, diagnosis, pathophysiology, and treatment
      for all cases of the ACS.

PMID- 24881702
TI  - Clinical awareness of intra-abdominal hypertension and abdominal compartment
      syndrome in 2007.
AB  - INTRODUCTION: There has been an exponentially increasing interest in intra
      abdominal hypertension (IAH). The aim of this review is to evaluate the evolution
      in clinical awareness of this syndrome. METHODS: A PubMed (U.S. National Library
      of Medicine) search and a ScienceDirect (Elsevier B.V.) search of recent
      literature were performed in order to assess clinical awareness of IAH and
      abdominal compartment syndrome (ACS). RESULTS: In total, 489 articles and 8
      clinical surveys have been identified. The results of the landmark papers and the
      surveys will be briefly discussed in this review. CONCLUSION: Clinical awareness
      of ACS is steadily increasing. It is time to pay attention to ACS, but further,
      it is time to move forward with therapeutic bundles in a multi-centered, outcome
      trial on IAH/ACS therapy in order to elevate IAH/ACS management to an
      international standard of care.

PMID- 24881703
TI  - Clinical significance of elevated intraabdominal pressure during common
      conditions and procedures.
AB  - INTRODUCTION: Pregnancy, obesity, peritoneal dialysis, pneumoperitoneum, prone
      position and application of positive end-expiratory pressure are associated with
      elevated intraabdominal pressure (IAP). OBJECTIVE: To review the relation between
      these conditions and procedures, and intraabdominal hypertension (IAH) or
      abdominal compartment syndrome (ACS). METHODS: Search of PubMed and Google
      Scholar and review of article bibliographies. RESULTS AND CONCLUSION: Only
      obesity, peritoneal dialysis, and pneumoperitoneum are associated with symptoms
      related to IAH and these symptoms are reversible.

PMID- 24881704
TI  - Effect of intra-abdominal pressure on respiratory mechanics.
AB  - INTRODUCTION: There has been an exponentially increasing interest in intra
      abdominal hypertension (IAH). The intra-abdominal pressure (IAP) markedly affects
      the function of the respiratory system. METHODS: This review will focus on the
      available literature from the past few years. A Medline and Pubmed search was
      performed in order to find an answer to the question "What is the impact of
      increased IAP on respiratory function in the critically ill?". RESULTS: In
      particular, increased IAP increases chest wall elastance (or decreases
      compliance) and promotes cranial shift of the diaphragm, with consequent
      reduction in lung volume and atelectasis formation. Compression of the lung
      parenchyma also triggers pulmonary infection. During general anaesthesia, in
      normal subjects, IAP does not affect the chest wall mechanics, but plays a
      relevant role in the caudal-cranial displacement of the abdominal content, the
      diaphragm and consequent changes in lung mechanics and function. In obese
      patients, the increased IAP is the major determinant of the reduction in lung
      volume, atelectasis formation and alterations in chest wall mechanics. In ARDS
      patients the measurement of IAP and chest wall mechanics is important for a
      better interpretation of respiratory mechanics, hemodynamics and appropriate
      setting of the ventilator. Furthermore, increased IAP promotes lung oedema,
      ventilator induced lung injury and reduced lymphatic flow in normal and diseased
      lungs. CONCLUSION: Increased IAP markedly affects respiratory function in such a
      way that it has an impact on daily clinical practise.

PMID- 24881705
TI  - The influence of intra-abdominal hypertension on the central nervous system:
      current insights and clinical recommendations, is it all in the head?
AB  - INTRODUCTION: Intra-abdominal hypertension (IAH) and abdominal compartment
      syndrome are a common occurrence in ICU patients. The deleterious effects of IAH
      on organ function are well known and increasingly appreciated in recent years,
      especially where renal and respiratory function are concerned. METHODS: This
      review will focus on the available literature from the last years. A Medline and
      PubMed search was performed in order to find an answer to the question "What is
      the impact of increased IAP on neurologic function in the critically ill?"
      RESULTS: The amount of data on the influence of IAH on the central nervous system
      is more scarce, but several animal and human studies have demonstrated a clear
      correlation between intra-abdominal pressure (IAP) and intracranial pressure
      (ICP). This correlation is probably due to transmission of the increased IAP to
      the thorax leading to increased intrathoracic, pleural pressure and central
      venous pressure, decreased venous return from the brain and increased ICP. This
      hypothesis is supported by the observation that the increase in ICP is abolished
      when a sternotomy and pleuropericardotomy are performed, and by the fact that
      abdominal decompression has produced good results in treating refractory
      intracranial hypertension (ICH) in patients with both IAH and ICH. CONCLUSIONS: A
      close relationship between IAP and ICP has been observed in several animal and
      human studies. The clinical impact of this association is dependent on the
      baseline ICP and the compensatory reserve of the patient. Some studies have
      reported good results in treating refractory ICH by abdominal decompression in
      patients with concomitant IAH. Monitoring of IAP and ICP in risk patients is
      essential.

PMID- 24881706
TI  - Cardiovascular implications of abdominal compartment syndrome.
AB  - Cardiovascular dysfunction and failure are commonly encountered in the patient
      with intra-abdominal hypertension or abdominal compartment syndrome. Accurate
      assessment and optimization of preload, contractility, and afterload, in
      conjunction with appropriate goal-directed resuscitation and abdominal
      decompression when indicated, are essential to restoring end-organ perfusion and
      maximizing patient survival. The validity of traditional hemodynamic
      resuscitation endpoints, such as pulmonary artery occlusion pressure and central
      venous pressure, must be reconsidered in the patient with intra-abdominal
      hypertension as these pressure-based estimates of intravascular volume have
      significant limitations in patients with elevated intra-abdominal pressure. If
      such limitations are not recognized, misinterpretation of the patient's cardiac
      status is likely, resulting in inappropriate and potentially detrimental therapy.
      Appropriate fluid administration is mandatory as under-resuscitation leads to
      organ failure and over-resuscitation the development of secondary abdominal
      compartment syndrome, both of which are associated with increased morbidity and
      mortality. Volumetric monitoring techniques have been proven to be superior to
      traditional intra-cardiac filling pressures in directing the appropriate
      resuscitation of this patient population. Calculation of the "abdominal perfusion
      pressure", defined as mean arterial pressure minus intra-abdominal pressure, has
      been shown to be a beneficial resuscitation endpoint as it assesses not only the
      severity of the patient's intra-abdominal hypertension, but also the adequacy of
      abdominal blood flow. Application of a goal-directed resuscitation strategy,
      including abdominal decompression when indicated, improves cardiac function,
      reverses end-organ failure, and minimizes intra-abdominal hypertension-related
      patient morbidity and mortality. 

PMID- 24881707
TI  - Hepatic function and non-invasive hepatosplanchnic monitoring in patients with
      abdominal hypertension.
AB  - A better understanding of intra-abdominal hypertension with relation to the liver
      is vital to the management of all forms of liver pathophysiology. Supporting good
      hepatic function within the critically ill patient is important not only in
      maintaining synthetic function, but also in avoiding the multi-organ
      complications of liver dysfunction. The resulting reduction in hepato-splanchnic
      blood flow (HSBF) observed with increasing intra-abdominal pressure has been
      clearly documented and seen to be exaggerated in animals with established liver
      disease. Unfortunately the tools required to measure this, remain difficult to
      apply routinely in the clinical setting and as such goal directed therapy to
      specifically improve the hepatosplanchnic circulation remains elusive. Given the
      documented effects of IAP on HSBF and the relatively high incidence of intra
      abdominal hypertension and the abdominal compartment syndrome within "liver
      patients" as a whole, close attention to IAP and timely correction by appropriate
      medical or surgical means would appear to be essential. 

PMID- 24881708
TI  - Renal implications of increased intra-abdominal pressure: are the kidneys the
      canary for abdominal hypertension?
AB  - INTRODUCTION: Increased intra-abdominal pressure (IAP) or intra-abdominal
      hypertension (IAH) is a cause of organ dysfunction in critically ill patients and
      is independently associated with mortality. The kidneys seem to be especially
      vulnerable to IAH induced dysfunction and renal failure is one of the most
      consistently described organ dysfunctions associated with IAH. The aim of this
      paper is to review the historical background, awareness, definitions,
      pathophysiologic implications and treatment options for IAP induced renal
      failure. METHODS: This review will focus on the available literature on IAH
      induced renal dysfunction. A Medline and PubMed search was performed in order to
      find an answer to the question "What is the impact of increased IAP on renal
      function in the critically ill?". The resulting references were included in the
      current review on the basis of relevance and scientific merit. RESULTS: Renal
      dysfunction in IAH is a multifactorial process. The mechanisms involved have not
      been clarified completely. However, decreased cardiac output, altered renal blood
      flow and hormonal changes have been implicated. Decompression seems to have a
      beneficial effect on renal dysfunction, although there are some conflicting data.
      This may be due to the fact that there is no consensus on indications for
      decompression, both in terms of IAP values and of timing. An overview of current
      literature is provided and some interesting leads for future research are
      suggested. CONCLUSION: IAH can cause renal dysfunction. Therefore, IAP
      measurements should be considered in our daily practice and preventive measures
      should be taken to avoid (deterioration of) renal failure in patients with IAH.
      Decompression may have a beneficial effect in patients with established IAH and
      renal failure.

PMID- 24881709
TI  - Abdominal compartment syndrome and acute pancreatitis.
AB  - Significant visceral edema associated with massive fluid resuscitation, paralytic
      ileus and formation of pancreatic ascites in patients with severe acute
      pancreatitis (SAP) can lead to abdominal compartment syndrome (ACS) that can
      contribute to the early development of multiple organ dysfunction syndrome
      (MODS), especially in the early stages of the disease. The prevalence of intra
      abdominal hypertension (IAH) in SAP is about 40% and a manifest ACS occurs in
      about 10% of the patients warranting close monitoring of intra-abdominal pressure
      (IAP) in all patients with the severe form of the disease. Although nonsurgical
      management utilizing percutaneous drainage of ascites or continuous
      hemodiafiltration may decrease IAP, most patients require decompressive
      laparostomy and temporary abdominal closure. The primary aim in managing the
      ensuing open abdomen is delayed fascial closure during initial hospitalization.
      On many occasions a planned hernia approach, either with early skin grafting over
      the exposed bowel or managing the ASC primarily with a subcutaneous linea alba
      fasciotomy, is the only available option. The development of ACS in patients with
      SAP seems to be associated with increased mortality. 

PMID- 24881710
TI  - The abdominal compartment syndrome in patients with burn injury.
AB  - INTRODUCTION: Intra-abdominal hypertension (IAH) and subsequent abdominal
      compartment syndrome (ACS) in burned patients is common. This sequence of events
      typically occurs in patients with larger burns receiving high volume fluid
      resuscitation. METHODS: A review of the literature was performed. The National
      Library of Medicine (PUBMED) was queried for "Burn" and "Abdominal Compartment
      Syndrome". Twenty-nine articles were retained for study. RESULTS: Abdominal
      pressure monitoring is appropriate in all patients with burns that require
      significant volume resuscitation (>30% total burned surface area- TBSA).
      Prevention of ACS in burns includes limiting fluid resuscitation, burn
      escharotomy, and percutaneous drainage when abdominal pressures are reaching
      perilous levels. Treatment includes all of the above and in addition,
      decompressive laparotomy when needed. However, despite decompressive laparotomy,
      mortality rates among burn victims with ACS remain unacceptably high. CONCLUSION:
      Increasing amounts of volume delivery are associated with an increased risk of
      IAH. Therefore, intra-abdominal pressure should be monitored in all burn patients
      requiring massive fluid resuscitation. Escharotomy, paracentesis, and
      decompressive laparotomy may all be needed to counter the side effects of
      appropriate fluid resuscitation in the severely burned patient. Nevertheless, the
      prognosis in burn patients developing ACS is grim.

PMID- 24881711
TI  - Outcomes of children with abdominal compartment syndrome.
AB  - INTRODUCTION: Abdominal compartment syndrome (ACS) is a problem across all
      critical care scenarios and is associated with a high mortality. It has not been
      well described in pediatric populations. OBJECTIVE: To describe the occurrence of
      ACS in a subset of critically ill pediatric patients and determine its effects on
      mortality and length of pediatric intensive care stay (PICU LOS). We also aimed
      to find predictors of mortality and development of ACS. SETTING: 25 bed tertiary
      pediatric intensive care unit. PATIENTS: PATIENTS less than 50 kg on mechanical
      ventilation and a urethral catheter. MEASUREMENTS: Intra-abdominal pressures
      (IAP) were monitored using the intra-vesical technique. ACS was defined as IAP of
      >12mmHg associated with new organ dysfunction or failure. Demographics,
      physiologic measures of organ dysfunction, PICU LOS and mortality were monitored.
      MAIN RESULTS: 14 (4.7%) of 294 eligible patients had ACS. Mortality was 50% among
      those with ACS versus 8.2% without (p<.001). PICU LOS stay did not differ between
      groups. No difference in mortality or PICU LOS was seen in primary versus
      secondary ACS or in patients who underwent abdominal decompression compared to
      those without decompression. IAP and ACS were independent predictors of mortality
      (odds ratio 1.53, 95% CI, 1.17 - 1.99 and 9.09, 95% CI, 1.07 - 76.84)
      respectively. IAP and a PRISM score of >=17 were predictive of developing ACS.
      CONCLUSIONS: ACS is a clinical problem that increases the risk of mortality in
      critically ill children. IAP and PRISM scores may help identify children likely
      to develop ACS.

PMID- 24881712
TI  - Acs in paediatrics.
AB  - Abdominal Compartment Syndrome (ACS) occurs relatively infrequent in a paediatric
      population when compared with adults. Overall mortality is still high. Also, the
      pathophysiologic mechanism that leads to ACS is different in children. In this
      review, we will present an overview on ACS in children admitted to a paediatric
      intensive care unit. 

PMID- 24881713
TI  - Lymphatic drainage between thorax and abdomen: please take good care of this well
      performing machinery....
AB  - INTRODUCTION: Patients with sepsis often receive large amounts of fluids and the
      presence of capillary leak, trauma or bleeding results in ongoing fluid
      resuscitation. This increases interstitial and intestinal edema and finally leads
      to intra-abdominal hypertension (IAH), which in turn impedes lymphatic drainage.
      Patients with IAH often develop secondary respiratory failure needing mechanical
      ventilation with high intrathoracic pressure or PEEP that might further alter
      lymphatic drainage. This review will try to convince the reader of the importance
      of the lymphatics in septic patients with IAH. METHODS: A Medline and PubMed
      literature search was performed using the terms "abdominal pressure", "lymphatic
      drainage" and "ascites formation". The references from these studies were
      searched for relevant articles that may have been missed in the primary search.
      These articles served as the basis for the recommendations below. RESULTS:
      Induction of sepsis with lesion of the capillary alveolar barrier results in an
      increased water gradient between the capillaries and the interstitium in the
      lungs. The drainage flow to the thoracic duct is initially increased in order to
      protect the lung and maintain the pulmonary interstitium as dry as possible,
      however this results in increased intrathoracic pressure. Sepsis also increases
      the permeability of the capillaries in the splanchnic beds. In analogy to the
      lungs the lymphatic flow in the splanchnic areas increases together with the
      pressure inside as a physiological response in order to limit the increase in
      IAP. At a critical IAP level (around 20 cmH2O) the lymph flow starts to decrease
      and the splanchnic water content progressively increases. The lymph flow from the
      abdomen to the thorax is progressively decreased resulting in increased
      splanchnic water content and ascites formation. The presence of mechanical
      ventilation with high PEEP reduces the lymph drainage further which together with
      the increase in IAP decreases the lymphatic pressure gradient in the splanchnic
      regions, with a further increase in water content and IAP triggering a vicious
      cycle. CONCLUSION: Although often overlooked the role of lymphatic flow is
      complex but very important to determine not only the fluid balance in the lung
      but also in the peripheral organs. Different pathologies and treatments can
      markedly influence the pathophysiology of the lymphatics with dramatic effects on
      endorgan function.

PMID- 24881714
TI  - Abdominal compartment syndrome and intraabdominal sepsis: two of the same kind?
AB  - BACKGROUND: Abdominal compartment syndrome and intra-abdominal hypertension are
      frequently associated with peritonitis. The aim of this study is to establish the
      relationship between intra-abdominal hypertension and intra-abdominal sepsis
      especially in critically ill patients. METHODS: Relevant information was
      identified through a Medline search (1966-October 2006). The terms used were
      "intra-abdominal sepsis", "peritonitis", "abdominal compartment syndrome", "intra
      abdominal hypertension" and "relaparotomy for sepsis". The search was limited to
      English- and French-language publications. RESULTS: Only a few clinical trials
      exist on this specific topic. Further investigations are required to define the
      incidence of intra-abdominal hypertension in intra-abdominal sepsis, and the
      prognostic impact of this setting and finally the potential specific treatment.
      Abdominal compartment syndrome is more likely linked to the abdominal surgery
      than to peritonitis itself. CONCLUSION: Intra-abdominal pressure monitoring can
      be valuable in critically ill patients with suspicion of persisting intra
      abdominal sepsis after surgical peritonitis treatment.

PMID- 24881715
TI  - Defining gastrointestinal failure.
AB  - INTRODUCTION: Gastrointestinal failure (GIF) has been postulated as the motor of
      multiple organ dysfunction syndrome (MODS) but is not commonly included among
      other organ failures in scoring systems identifying MODS. MATERIALS AND METHODS:
      Relevant articles and published reviews were identified and analyzed through a
      PubMed search of English language literature on gastrointestinal problems.
      RESULTS AND DISCUSSION: Wide variability in terms and definitions was observed.
      Data on the incidence of GIF and its impact on mortality in critically ill
      patients are controversial. Very few objectively measurable variables of GI
      function are available. Most of the definitions of GIF are diagnosis-, but not
      function-based. Diagnosis-based approach to GIF differs significantly from the
      function-based assessment of other organ failures and has not justified itself
      over time. CONCLUSIONS: There is no consensus on definition of GIF and different
      medical specialties have different approaches. Development of a proper definition
      of GIF is warranted.

PMID- 24881716
TI  - New and old tools for abdominal imaging in critically ill patients.
AB  - Diagnostic imaging technology has advanced considerably during the past two
      decades. Different imaging techniques have been proposed for abdominal imaging in
      critically ill patients like plain radiography, sonography, computed tomography
      (CT), magnetic resonance and positron emission tomography. Sonography has been
      proven to be effective to detect free intra-peritoneal fluid and it is considered
      one of the primary diagnostic modalities for abdominal evaluation for trauma
      assessment. In our opinion sonography should replace other invasive techniques to
      rapidly triage blunt trauma patients with unstable vital signs and examine the
      peritoneal cavity as a site of major haemorrhage to expedite exploratory
      laparotomy. On the other hand, CT has become the imaging modality of choice in
      hemodynamically stable patients with multisystem blunt and penetrating trauma.
      New developments in the quantitative analysis of the CT images will improve our
      knowledge of pathophysiology, diagnostic and therapeutic management of abdominal
      pathologies in critically ill patients. 

PMID- 24881717
TI  - Cardiac ultrasound and abdominal compartment syndrome.
AB  - This review focuses on the available literature published about the evaluation of
      haemodynamic consequences of the abdominal compartment syndrome (ACS). Animal and
      clinical studies described decreased venous return, systemic vasoconstriction,
      systolic and diastolic dysfunction of left and right ventricles. Doppler
      echocardiography is a non-invasive bedside procedure which provides a complete
      haemodynamic evaluation of patients with ACS. Despite numerous evaluations in
      anesthesia during laparoscopic surgery, the use of echocardiography remains
      scarce in critically ill patients with ACS. 

PMID- 24881718
TI  - ICU management of the patient with intra-abdominal hypertension: what to do, when
      and to whom?
AB  - INTRODUCTION: Intra-abdominal hypertension (IAH) and abdominal compartment
      syndrome (ACS) are increasingly recognised to be a contributing cause of organ
      dysfunction and mortality in critically ill patients. The number of publications
      describing and researching this phenomenon is increasing exponentially but there
      are still very limited data about treatment and outcome. METHODS: This review
      will focus on the available literature from the last years. A Medline and PubMed
      search was performed using the search terms "abdominal compartment syndrome" and
      "treatment". RESULTS: This search yielded 437 references, most of which were not
      relevant to the subject of this paper. The remaining abstracts were screened and
      selected on the basis of relevance, methodology and number of cases. Full text
      articles of the selected abstracts were used to supplement the authors' expert
      opinion and experience. The abdomino-thoracic transmission of pressure has direct
      clinical consequences on the cardiovascular, respiratory and central nervous
      systems in terms of monitoring and management. These interactions are discussed
      and treatment recommendations are made. IAH-induced renal dysfunction is
      addressed as a separate issue. Finally, an overview of non-invasive measures to
      decrease IAP is given. CONCLUSION: This paper describes current insights on
      management of IAP induced organ dysfunction and lists the most widely used and
      published non-invasive techniques to decrease IAP with their limitations and
      pitfalls.

PMID- 24881719
TI  - Abdomino-thoracic transmission during acs: facts and figures.
AB  - Elevated intra-abdominal pressure (IAP) exerts effects not only on intra
      abdominal organs, but also on organs distant to the abdominal compartment.
      Abdomino-thoracic interaction during intra-abdominal hypertension (IAH) or
      abdominal compartment syndrome (ACS) interferes with pulmonary, cardiovascular
      and cerebral function. In accordance with recent guidelines, IAH is defined as
      IAP above 12 mmHg and ACS as IAP more than 20 mmHg with one or more new organ
      failures. In this review we will first discuss the effects of elevated IAP on
      pulmonary dynamics and the relevance for interpreting airway pressures and
      adjusting ventilator settings. We will then discuss the interaction between
      abdomino-thoracic pressure transmission and global haemodynamics, the knowledge
      of which is necessary for correct assessment of cardiac preload and to optimize
      fluid therapy in the setting of IAH/ACS. A discussion on the relationship between
      increased IAP, increased intracranial pressure (ICP) and decreased cerebral
      perfusion pressure (CPP) will follow. Finally, we will review ventilator-induced
      thoracic pressure swings and their transmission to the abdominal compartment. 

PMID- 24881720
TI  - Management of open abdomen.
AB  - Non-closure of abdominal fascia and the resultant open abdomen after laparotomy
      has become a major advance in the management of critically ill or injured
      patients. The benefits of open abdomen are many and include the prevention of
      intra-abdominal hypertension and the consequent abdominal compartment syndrome.
      Appropriately and exquisitely managed, it can provide all the benefits and
      prevent highly morbid complications of leaving the abdomen open. This review will
      provide some insights into such management. 

PMID- 24881721
TI  - Temporary abdominal closure.
AB  - The increasing recognition of abdominal compartment syndrome's adverse effect on
      patient outcome has been coupled with our expanding knowledge of techniques of
      temporary abdominal closure. Temporary abdominal closure can be used
      prophylactically to prevent abdominal compartment syndrome developing and more
      commonly in the treatment of patients with progressing or advanced abdominal
      compartment syndrome. The preferred technique involves a negative suction
      dressing protecting the fascial and skin edges, collecting intraperitoneal fluid
      and reducing contamination. Attempts of early closure will facilitate recovery. 

PMID- 24881722
TI  - Modified sandwich vacuum pack technique for temporary closure of abdominal
      wounds: an african perspective.
AB  - INTRODUCTION: South Africa has very high levels of accidental trauma as well as
      interpersonal violence. There are more admissions for trauma in South Africa than
      for any other disease; therefore it can be regarded as the Number 1 disease in
      the country. Complex abdominal injuries are common, requiring specific management
      techniques. The aim is to document our experience with the Modified Sandwich
      Vacuum Pack technique for temporary closure of abdominal wounds. METHODS: After
      providing a short historical overview, we will demonstrate the technique which we
      carefully adapted over the last decade to the present Modified Sandwich Vacuum
      Pack technique. RESULTS: In the last 5 years we utilized our Modified Sandwich
      Vacuum Pack technique 153 times in 69 patients. Five (5) patients were under the
      age of 12 years. In the patient group over 12 years the most common indication
      for using our technique were penetrating injuries (40), abdominal sepsis (28),
      visceral edema (10), abdominal compartment syndrome (9), abdominal packs (6),
      Abdominal wall defects (2). In the group under 12-years the 2 children had liver
      ruptures (posttraumatic) and 3 liver transplantations. The average cost for the
      materials used with our technique was ZAR 96. (10 Euro and 41 cents). CONCLUSION:
      In our experience the Modified Sandwich Vacuum Pack technique is an effective,
      cheap methodology to deal with open abdomens in the African setting. A drawback
      may be the technical expertise required, particular in centers dealing with low
      numbers of complex abdominal trauma.

PMID- 24881723
TI  - New developments in abdominal wall reconstruction after abdominal compartment
      syndrome decompression.
AB  - The acute abdominal compartment syndrome (ACS) is most often treated with
      surgical abdominal decompression. After the acute phase, primary closure of the
      abdominal wall may not be possible, due to tissue loss and retraction of the
      abdominal wall and its musculofascial components. This article gives an update of
      the reconstructive ladder for abdominal wall defects. Because of improved
      intensive care treatment and wound dressing, reconstruction can usually be
      delayed until infection and oedema have settled. Recent developments in
      bioprosthetics and new surgical techniques like component separation make better
      results with less donor site morbidity possible. However, there is still a place
      for local and distant flaps. 

PMID- 24881724
TI  - What is the best animal model for acs?
AB  - INTRODUCTION: Current treatment of the abdominal compartment syndrome (ACS) is
      based on consensus definitions but several questions regarding fluid regime or
      critical level of intra-abdominal hypertension (IAH)) remain unsolved. It is
      questionable whether these issues can be addressed in prospective randomized
      trials in the near future. This review aimed to summarize current animal models
      and to outline requirements for the best model. METHODS: PubMed(r) data base was
      searched for articles describing animal models of ACS. RESULTS: 25 articles were
      found. ACS in animals has not been defined yet. Investigations varied
      considerably regarding the experimental design. Animals were rats, rabbits, dogs
      and pigs with a bodyweight from 200g to 70 kg. IAP increase varied from 20 to 50
      mmHg. The time period of IAH ranged between 30 min and 24h. The time between the
      IAH insult and organ dysfunction varied between 15 min and 18h. Investigations
      demonstrated that IAH is able to induce loss of intravascular volume, organ
      hypoperfusion, ischemic organ damage and multiple organ failure within 4 to 6h.
      CONCLUSION: In contrast to IAH or pneumoperitoneum for surgical exposure, ACS in
      an animal may be stated if an artificially increased IAP leads to circulatory,
      respiratory and renal insufficiency. A next step in animal research would be the
      development of a "pathological" model in which haemorrhage or systemic
      inflammation together with resuscitation lead to abdominal fluid accumulation and
      increased intra-abdominal pressure.

PMID- 24881725
TI  - Abstracts of invited lectures.

PMID- 24881726
TI  - Abstracts of oral presentations.

PMID- 24881727
TI  - Abstracts of study protocols.

PMID- 24881728
TI  - Abstracts of mini-papers.

PMID- 24881729
TI  - Abstracts of posters.

PMID- 24881731
TI  - Clinical characteristics and treatment outcomes of nineteen Japanese patients
      with gastrointestinal bezoars.
AB  - OBJECTIVE: To analyze the clinical characteristics of patients with
      gastrointestinal bezoars and their response to therapy. Patients We
      retrospectively reviewed the cases of 19 patients diagnosed with gastrointestinal
      bezoars at the Okayama University Graduate School of Medicine, Dentistry and
      Pharmaceutical Sciences or one of 15 collaborating institutions between December
      2004 and August 2013. We investigated the epidemiology and etiology of the
      gastrointestinal bezoars by determining the gender, age at diagnosis, medical
      history, symptoms, complications, modalities used for diagnosis, treatments,
      outcomes and bezoar location, color and contents. RESULTS: There were 17 patients
      with gastric bezoars and two patients with small intestinal bezoars. All patients
      were 62 years of age or older, except for one case of a trichobezoar in a 10-year
      old patient. Some of the patients had a history of surgery of any part of the
      gastrointestinal tract (n=5) and/or diabetes mellitus (n=2). The two patients
      with small intestinal bezoars required surgical removal in order to relieve
      ileus. Approximately one-half of the patients with gastric bezoars had
      ulcerations in the stomach (9/17 patients, 52.9%) and/or gastrointestinal
      bleeding (8/17, 47.1%). Endoscopic fragmentation was performed in 10 patients,
      whereas bezoar dissolution was achieved with a gastroprokinetic agent (n=1) and
      without any treatment (n=3) in the remaining cases. CONCLUSION: As previously
      reported, elderly individuals with a positive history of surgery and/or diabetes
      mellitus were observed in this bezoar patient series. Gastric ulcers and
      gastrointestinal bleeding were frequently observed. The majority of patients
      underwent endoscopic fragmentation, while spontaneous resolution of the gastric
      bezoar was observed in several cases.

PMID- 24881732
TI  - Proton pump inhibitor treatment decreases the incidence of upper gastrointestinal
      disorders in elderly Japanese patients treated with NSAIDs.
AB  - OBJECTIVE: The Japanese health insurance system approved the use of proton pump
      inhibitors (PPIs) for the prevention of peptic ulcers in patients using low-dose
      aspirin (LDA) and/or non-steroidal anti-inflammatory drugs (NSAIDs). However,
      many orthopedists and physicians do not prescribe PPIs to elderly patients with
      atrophic gastritis. The aim of this study was to determine whether PPIs are
      effective in preventing gastrointestinal mucosal injury in elderly Japanese
      patients with atrophic gastritis. METHODS: We examined the associations between
      the use of antiulcer drugs and endoscopic findings in elderly Japanese patients
      using LDA or NSAIDs. Patients We evaluated 100 patients using LDA and 58 patients
      using non-aspirin NSAIDs 65 years of age or older. All patients underwent upper
      GI endoscopy to detect the presence of open ulcers and hemorrhagic lesions and
      assess the extent of atrophic gastritis. RESULTS: Among the patients using LDA,
      the prevalence of open ulcers was significantly lower in the patients using PPIs
      than in those using mucosal protective agent only and those not receiving
      antiulcer treatment (p<0.001). Among the patients using NSAIDs, the patients
      treated with PPIs exhibited a significantly lower incidence of open ulcers than
      the patients not receiving antiulcer treatment (p=0.012). Open-type atrophic
      gastritis was observed in nearly 70% of the patients. CONCLUSION: The use of PPI
      treatment is advisable in order to prevent the discontinuation of LDA or NSAIDs
      due to the development of gastrointestinal disorders in elderly patients with
      atrophic gastritis.

PMID- 24881733
TI  - Prognostic value of bronchoalveolar lavage in patients with non-HIV pneumocystis
      pneumonia.
AB  - OBJECTIVE: Non-HIV patients with pneumocystis pneumonia (PCP) have a poor
      prognosis. We aimed to evaluate the prognostic factors for in-hospital mortality
      in terms of the clinical findings, including the results of bronchoalveolar
      lavage fluid (BALF)-analyses, in non-HIV PCP patients. METHODS: We
      retrospectively reviewed non-HIV PCP patients diagnosed using bronchoalveolar
      lavage between April 2006 and July 2012. For patients with a poor respiratory
      status, noninvasive positive pressure ventilation (NPPV) was used during the
      bronchoalveolar lavage (BAL) procedure. Data regarding demographics, laboratory
      findings and the prognosis were evaluated. RESULTS: A total of 29 non-HIV PCP
      patients were analyzed. NPPV was carried out safely and successfully in 12
      patients during the BAL procedure. Twelve patients (41%) died. The multivariate
      logistic regression analysis identified only BALF neutrophilia to be a
      significant prognostic factor determining in-hospital mortality. The log-rank
      test showed that the patients with BALF neutrophilia (>= 31%) had a significantly
      lower survival rate than the other patients (p=0.001). CONCLUSION: Only BALF
      neutrophilia was found to be a significant predictor of survival in patients with
      non-HIV PCP. Our data also emphasize the significance of performing BAL in such
      patients, as it provides both diagnostic and prognostic information.

PMID- 24881734
TI  - Serial QuantiFERON TB-2G testing over a four-year period in healthcare workers at
      a city hospital.
AB  - OBJECTIVE: To evaluate the performance and practicality of QuantiFERON TB-2G (QFT
      2G) testing for screening healthcare workers (HCWs) at a city hospital in Japan
      without a tuberculosis (TB)-specific ward. METHODS: We performed a chart review
      of 951 HCWs (251 men and 700 women) who underwent QFT-2G testing as a part of
      their pre-employment or annual employee screening between April 2007 and March
      2010. RESULTS: The initial QFT-2G test was interpreted as positive in 28 (2.9%)
      HCWs, negative in 884 HCWs (92.9%) and indeterminate in 39 HCWs (4.1%). During
      the four-year study period, 37 HCWs were diagnosed as being positive at least
      once. Nine (0.98%) of the 923 HCWs with indeterminate or negative results on the
      initial testing converted to a positive status, including 6/479 (1.25%) nurses,
      2/100 (2.0%) office staff members and 1/147 (0.68%) physicians. No HCWs with a
      positive result had a history of tuberculosis (TB) or any apparent contact with
      active TB patients and did not opt for treatment of latent TB. Seven (25%) of the
      28 HCWs who were determined to be positive on the initial testing reverted to an
      indeterminate or negative status. CONCLUSION: In a series of annual serial QFT-2G
      tests, some HCWs exhibited conversion and/or reversion. Therefore, caution is
      required when interpreting mild fluctuations in interferon-gamma responses.

PMID- 24881735
TI  - Signet-ring cell carcinoma of the gallbladder complicated by pulmonary tumor
      thrombotic microangiopathy.
AB  - Biliary drainage was performed in a 71-year-old man with obstructive jaundice of
      unknown origin; however, he died due to acute pulmonary failure. At autopsy,
      proliferation of adenocarcinoma cells was observed in the gallbladder mucosa
      transitioning from isolated signet-ring cell carcinoma (SRCC) to the subserosa
      and bile ducts without growth toward the gallbladder lumen. Furthermore,
      fibrocellular intimal proliferation, tumor emboli and organized thrombi were
      observed in the small pulmonary arteries. The final diagnosis was gallbladder
      carcinoma complicated by SRCC associated pulmonary tumor thrombotic
      microangiopathy (PTTM). PTTM may present as rapidly progressive dyspnea, and a
      high level of clinical suspicion is required to make the differential diagnosis. 

PMID- 24881736
TI  - Nephrotic-range proteinuria and interstitial nephritis associated with the use of
      a topical loxoprofen patch.
AB  - A 76-year-old woman with a history of lumbar fracture and marked proteinuria,
      bilateral pitting edema, malaise and pruritus was referred for an evaluation of
      an impaired renal function. A renal biopsy led to a tentative diagnosis of acute
      interstitial nephritis (AIN) with minimal change disease caused by nonsteroidal
      anti-inflammatory drugs (NSAIDs). Following the discontinuation of oral NSAIDs,
      the patient's symptoms disappeared spontaneously. However, nephrotic-range
      proteinuria relapsed one month after discharge, following loxoprofen patch use.
      The withdrawal of the topical loxoprofen patches once again resulted in the
      disappearance of all symptoms. This is the first case report of nephrotic-range
      proteinuria and AIN secondary to topical NSAID patch use. 

PMID- 24881737
TI  - Deterioration of the immune response induced by sulfamethoxazole-trimethoprim in
      a rheumatoid arthritis patient with Pneumocystis jirovecii pneumonia.
AB  - A 73-year-old woman with rheumatoid arthritis treated with methotrexate and
      prednisolone was admitted with dyspnea and ground-glass opacity on chest CT. We
      diagnosed her with Pneumocystis jirovecii pneumonia (PCP) based on a positive PCR
      analysis of Pneumocystis jirovecii and the presence of cysts in bronchoalveolar
      lavage fluid. The PaO2 was 74.7 Torr on room air, and treatment with
      sulfamethoxazole-trimethoprim only was initiated. The hypoxemia and ground-glass
      opacity increased on hospital day 3, and the administration of adjunctive steroid
      therapy resulted in an improvement in the patient's condition. Although patients
      with PCP with HIV infection and hypoxemia are often treated with adjunctive
      steroid therapy to prevent adverse immune reactions, the efficacy of additive
      steroid administration in case of non-HIV PCP has not been established. 

PMID- 24881738
TI  - Development of multi-organ involvement including a left atrial myxoma-like lesion
      in a patient with granulomatosis with polyangiitis.
AB  - A 76-year-old woman suffering from granulomatosis with polyangitis (GPA)
      developed organizing pneumonia with positive antineutrophil cytoplasmic
      antibodies and microscopic hematuria. Prednisolone improved the hematuria and
      radiological findings; however, after tapering the dose of prednisolone, a
      posterior left atrial wall mass was detected in association with a fever. Both
      regressed spontaneously, although secretory otitis media and sinusitis were
      noted; the resected sinusitis specimen exhibited vasculitis highly suggestive of
      GPA. The clinical picture of GPA with multi-organ involvement can vary.
      Recognizing the various manifestations of GPA is therefore necessary in order to
      provide an appropriate diagnosis and disease management. 

PMID- 24881739
TI  - Perianal metastasis of non-small cell lung cancer.
AB  - We herein present the case of a 36-year-old woman who developed perianal
      metastasis of non-small cell lung cancer that was diagnosed based on the presence
      of symptoms mimicking a hemorrhoid. The patient initially underwent radiotherapy
      for a left superior sulcus tumor, then subsequently complained of a perianal mass
      that had prolapsed and bled. The tumor was removed via resection. Histologically,
      the mass was diagnosed as poorly differentiated carcinoma and considered to be a
      metastatic lesion arising from the primary lung cancer. 

PMID- 24881740
TI  - Two cases of autoimmune hemolytic anemia secondary to brucellosis: a review of
      hemolytic disorders in patients with brucellosis.
AB  - Brucellosis is a worldwide zoonotic disease associated with hemolytic
      complications, including thrombotic microangiopathy (TMA) and hemolytic anemia.
      Autoimmune hemolytic anemia (AIHA) is a rare clinical presentation of this
      disease. In this report, we describe the cases of two patients with brucellosis
      who presented with Coombs-positive AIHA. We also include a review of the
      literature on the hemolytic complications of brucellosis. Both patients were
      successfully treated with a combination of doxycycline and rifampicin in addition
      to steroids. In the medical literature, there are several cases of TMA associated
      with brucellosis, although only a few cases of Coombs test-positive AIHA have
      been reported. Antibiotic therapy is the mainstay of treatment, and the selection
      of antibiotics and duration of treatment do not differ between brucellosis
      patients with and without hemolysis. Although rare, the potential for brucellosis
      should always be kept in mind in patients who present with hemolysis, especially
      those living in areas where brucellosis is endemic. 

PMID- 24881730
TI  - Enzalutamide in metastatic prostate cancer before chemotherapy.
AB  - BACKGROUND: Enzalutamide is an oral androgen-receptor inhibitor that prolongs
      survival in men with metastatic castration-resistant prostate cancer in whom the
      disease has progressed after chemotherapy. New treatment options are needed for
      patients with metastatic prostate cancer who have not received chemotherapy, in
      whom the disease has progressed despite androgen-deprivation therapy. METHODS: In
      this double-blind, phase 3 study, we randomly assigned 1717 patients to receive
      either enzalutamide (at a dose of 160 mg) or placebo once daily. The coprimary
      end points were radiographic progression-free survival and overall survival.
      RESULTS: The study was stopped after a planned interim analysis, conducted when
      540 deaths had been reported, showed a benefit of the active treatment. The rate
      of radiographic progression-free survival at 12 months was 65% among patients
      treated with enzalutamide, as compared with 14% among patients receiving placebo
      (81% risk reduction; hazard ratio in the enzalutamide group, 0.19; 95% confidence
      interval [CI], 0.15 to 0.23; P<0.001). A total of 626 patients (72%) in the
      enzalutamide group, as compared with 532 patients (63%) in the placebo group,
      were alive at the data-cutoff date (29% reduction in the risk of death; hazard
      ratio, 0.71; 95% CI, 0.60 to 0.84; P<0.001). The benefit of enzalutamide was
      shown with respect to all secondary end points, including the time until the
      initiation of cytotoxic chemotherapy (hazard ratio, 0.35), the time until the
      first skeletal-related event (hazard ratio, 0.72), a complete or partial soft
      tissue response (59% vs. 5%), the time until prostate-specific antigen (PSA)
      progression (hazard ratio, 0.17), and a rate of decline of at least 50% in PSA
      (78% vs. 3%) (P<0.001 for all comparisons). Fatigue and hypertension were the
      most common clinically relevant adverse events associated with enzalutamide
      treatment. CONCLUSIONS: Enzalutamide significantly decreased the risk of
      radiographic progression and death and delayed the initiation of chemotherapy in
      men with metastatic prostate cancer. (Funded by Medivation and Astellas Pharma;
      PREVAIL ClinicalTrials.gov number, NCT01212991.).

PMID- 24881741
TI  - Acute myeloid leukemia concurrent with spinal epidural extramedullary myeloid
      sarcoma accompanied by a high CD25 expression and the FLT3-ITD mutation.
AB  - Myeloid sarcoma (MS) is an extramedullary myeloid tumor that sometimes presents
      with antedating systemic leukemia, leading physicians to the misdiagnosis of
      lymphoma. CD25 is expressed in 13% of patients with acute myeloid leukemia (AML),
      and its expression is associated with FLT3-ITD mutations, an elevated serum
      soluble interleukin 2 receptor (sIL-2R) level and a lower survival rate. However,
      there are no reports concerning the relationship between MS and the CD25
      expression. We herein report a case of AML accompanied by thoracic epidural MS
      with a high CD25 expression, the FLT3-ITD mutation and an extremely elevated
      serum sIL-2R level in a 59-year-old man who presented with paraplegia. 

PMID- 24881742
TI  - Azacitidine-associated acute interstitial pneumonitis.
AB  - Azacitidine is the first-line therapeutic option for myelodysplastic syndrome
      (MDS). This report describes a case of MDS in a patient who developed fatal acute
      interstitial pneumonitis (AIP) after the first seven-day course of intravenous
      azacitidine (75 mg/m(2)/day) treatment. A review of previous and present studies
      of azacitidine-associated AIP suggests that azacitidine may cause life
      threatening AIP during or after the first seven-day course of treatment, with
      pyrexia commonly preceding AIP. Although the non-hematologic adverse events
      associated with azacitidine are generally relatively mild, further accumulation
      of evidence may help to make an earlier diagnosis of azacitidine-associated AIP. 

PMID- 24881743
TI  - Successful bortezomib/dexamethasone induction therapy with lenalidomide in an
      elderly patient with primary plasma cell leukemia complicated by renal failure
      and pulmonary hypertension.
AB  - Primary plasma cell leukemia (PPCL) is a rare disease that progresses rapidly. In
      such cases, it is difficult to achieve remission, and early intensive
      chemotherapy is recommended. We herein describe the case of a 76-year-old man
      with PPCL complicated by renal failure and pulmonary hypertension.
      Bortezomib/dexamethasone induction therapy with lenalidomide was administered in
      association with continuous hemodiafiltration (CHDF). Complete remission was
      achieved after a single course of treatment, resulting in the cessation of CHDF.
      With the patient in remission, the administration of beraprost and bosentan
      resulted in improvements in the pulmonary hypertension. The results of this case
      report support the use of bortezomib/lenalidomide/dexamethasone combination
      therapy as an effective treatment for elderly PPCL patients with various
      complications. 

PMID- 24881744
TI  - Rheumatoid arthritis/methotrexate-associated primary cutaneous diffuse large B
      cell lymphoma, leg type.
AB  - This report concerns a 62-year-old man with primary cutaneous diffuse large B
      cell lymphoma (PCLBCL), leg type that developed during methotrexate (MTX)
      treatment for rheumatoid arthritis (RA). Several tumors were observed on the left
      lower leg. A histological analysis showed diffuse proliferation of large
      neoplastic B-cells that were immunophenotypically CD10-/MUM1+/BCL6-/BCL2+ and
      cytogenetically had IgH/c-MYC translocation without translocation involving BCL6
      or IgH/BCL2. No evidence of Epstein-Barr virus (EBV) infection was found. The
      discontinuation of MTX resulted in a 20-month disease-free period. No previous
      cases of PCLBCL, leg type associated with RA or MTX therapy have been reported.
      The phenotypes of our patient were partly different from those of typical PCLBCL,
      leg type or RA/MTX-associated lymphoma. 

PMID- 24881745
TI  - Transient hemiparesis and hemianesthesia in an atypical case of adult-onset
      clinically mild encephalitis/ encephalopathy with a reversible splenial lesion
      associated with adenovirus infection.
AB  - We herein report the case of a previously healthy 24-year-old Japanese woman who
      developed adult-onset clinically mild encephalitis/encephalopathy with a
      reversible splenial lesion (MERS) presenting with hemiparesis and hemianesthesia
      secondary to adenovirus infection. The patient's neurological symptoms and the
      lesion in the splenium resolved within 17 days without therapy. The radiographic
      features and clinical course observed in this case were consistent with a
      diagnosis of MERS; however, the only neurological symptoms were hemiparesis and
      hemianesthesia. This is the first reported case of MERS involving only
      hemiparesis and hemianesthesia at onset. This case suggests that a diagnosis of
      MERS should be suspected in patients with hemiparesis and hemianesthesia,
      especially when these conditions are preceded by infection. 

PMID- 24881746
TI  - Hepatitis C virus-associated neuropathy accompanied by eosinophilic vasculitis
      and granuloma formation.
AB  - We herein report the case of a patient with hepatitis C virus (HCV)-associated
      neuropathy with atypical pathological findings of a biopsied sural nerve. A 48
      year-old man was admitted for a gait disturbance. Purpura and edema on the legs
      and hyperalgesia on the distal extremities were noted. The plasma HCV viral load
      was high, and cryoglobulin was positive. In the biopsied sural nerve,
      perivascular eosinophilic infiltration was associated with extravascular
      granuloma formation in the epineurium. The patient's symptoms disappeared
      following treatment with interferon-alpha and ribavirin. The present case
      suggests that HCV infection can lead to peripheral neuropathy associated with
      eosinophilic infiltration and granuloma formation. 

PMID- 24881747
TI  - Perivasculitic panencephalitis with relapsing polychondritis: an autopsy case
      report and review of previous cases.
AB  - We herein report an autopsy case of relapsing polychondritis encephalitis
      coexisting with a Lewy body pathology and also review previous autopsy cases. A
      59-year-old man exhibited a tremor of the right hand, small-steppage gait and
      bradykinesia. Five years later, he presented with relapsing auricular chondritis
      and scleritis and subsequently showed exacerbation of extrapyramidal symptoms. A
      histological examination revealed perivascular lymphocytic cuffing and
      infiltration in the small vessels, as well as loss of nerve cells and gliosis in
      the basal ganglia, insular gyrus and medial temporal lobe. The present case was
      characterized by perivasculitic panencephalitis and the coexistence of a Lewy
      body pathology, which may have augmented the patient's parkinsonism. 

PMID- 24881748
TI  - Primary central nervous system cytotoxic T-cell lymphoma mimicking demyelinating
      disease.
AB  - A 40-year-old man visited to our hospital due to progressive right hemiparesis.
      Magnetic resonance imaging demonstrated a heterogeneous contrast-enhanced lesion
      in the left basal ganglia with compression of the ventricles. A brain biopsy did
      not demonstrate central nervous system (CNS) lymphoma, although acute
      demyelination was observed. Despite the administration of steroids, the lesion
      increased in size, and the patient died three months after admission. An autopsy
      disclosed perivascular and parenchymal infiltration of lymphoma cells. An
      immunohistochemical analysis showed that the lesion was a cytotoxic T-cell
      lymphoma. This case indicates that the development of primary CNS lymphoma of
      this immunophenotype may be preceded by demyelination with subsequent rapid
      progression, thus requiring a careful evaluation and meticulous diagnosis. 

PMID- 24881749
TI  - Neuroleptic malignant syndrome induced by combination therapy with tetrabenazine
      and tiapride in a Japanese patient with Huntington's disease at the terminal
      stage of recurrent breast cancer.
AB  - We herein describe the case of an 81-year-old Japanese woman with neuroleptic
      malignant syndrome that occurred 36 days after the initiation of combination
      therapy with tiapride (75 mg/day) and tetrabenazine (12.5 mg/day) for
      Huntington's disease. The patient had been treated with tiapride or tetrabenazine
      alone without any adverse effects before the administration of the combination
      therapy. She also had advanced breast cancer when the combination therapy was
      initiated. To the best of our knowledge, the occurrence of neuroleptic malignant
      syndrome due to combination therapy with tetrabenazine and tiapride has not been
      previously reported. Tetrabenazine should be administered very carefully in
      combination with other neuroleptic drugs, particularly in patients with a
      worsening general condition. 

PMID- 24881750
TI  - Pineal malignant B-cell lymphoma with lower cranial nerve involvement.
AB  - A 62-year-old man was admitted to our hospital complaining of dysphagia and
      hoarseness that had persisted for five days. A neurological examination indicated
      bulbar palsy. Brain magnetic resonance imaging showed thickening of cranial
      nerves IX, X and XI, in addition to pineal body enlargement with diffuse contrast
      enhancement. A tumor biopsy overriding the spinal root of the right XIth cranial
      nerve was performed. The histologic analysis confirmed a diagnosis of diffuse
      large B-cell lymphoma. Malignant lymphoma should be considered in the
      differential diagnosis of pineal region tumors. Furthermore, obtaining
      histological confirmation is crucial for making proper management decisions. 

PMID- 24881751
TI  - Steroid-sparing effects of etanercept in a patient with steroid-dependent adult
      onset Still's disease.
AB  - We herein report the case of an 84-year-old man with steroid-dependent adult
      onset Still's disease (AOSD) whose daily steroid dose was successfully tapered
      after etanercept treatment. The corticosteroids worked well initially, and the
      patient went into remission promptly; however, he suffered a relapse due to
      steroid tapering. Because treatment with cyclosporine and methotrexate was
      ineffective, reducing the steroid dose was difficult, and the corticosteroids
      induced myopathy and diabetes. However, steroid tapering was accomplished in
      combination with etanercept therapy, and the patient's steroid-induced side
      effects disappeared. Etanercept should therefore be considered as a steroid
      sparing treatment option in patients with steroid-responsive, steroid-dependent
      AOSD. 

PMID- 24881752
TI  - A rare case of septic pulmonary embolism caused by infection-associated catheter
      removal in a patient with Hodgkin's lymphoma.
AB  - As a reflection of the considerable increase in the number of cancer patients
      treated with chemotherapy, indications for the use of implanted venous catheters
      are rapidly growing. However, in some cases, implanted venous catheters induce
      unwelcome complications. We herein report a rare case of septic pulmonary
      embolism (SPE) caused by local infection-associated catheter removal during the
      administration of ABVd combination chemotherapy consisting of adriamycin,
      bleomycin, vinblastine and dacarbazine in a patient with Hodgkin's lymphoma of
      the mixed cellularity type. During the course of treatment with chemotherapy
      administered via implanted venous catheters, think it is crucial to monitor for
      the potential occurrence of SPE. 

PMID- 24881753
TI  - Campylobacter fetus bacteremia with purulent pleurisy in a young adult with
      primary hypogammaglobulinemia.
AB  - A 24-year-old man presented with fever and pleural effusion predominantly
      containing lymphocytes. Cultures of the pleural effusion and blood revealed
      Campylobacter fetus, and laboratory studies showed a low serum level of
      immunoglobulin. The patient was diagnosed with C. fetus pleuritis, bacteremia and
      primary hypogammaglobulinemia, and subsequent treatment with meropenem and
      immunoglobulin improved his condition. Although the underlying cause of the
      primary hypogammaglobulinemia remains unclear, the patient's status improved
      under immunoglobulin replacement therapy. C. fetus pleuritis is a rare infectious
      disease usually observed in immunocompromised hosts. We herein describe the first
      report of C. fetus pleuritis in a young adult with primary hypogammaglobulinemia.

PMID- 24881754
TI  - Diabetic muscle infarction in a patient admitted to the cardiac ward.
AB  - Diabetic muscle infarction (DMI) is a rare complication of long-standing diabetes
      mellitus. This is the first case of DMI reported by cardiologists. A 49-year-old
      patient with a history of diabetes and hypertension for only two years was
      admitted to the cardiac ward due to pain in the left thigh with pitting edema in
      both lower extremities. Magnetic resonance imaging finally confirmed the presence
      of DMI in the left thigh, which was improved by treatment with anticoagulants,
      analgesics and rest. However, the typical clinical symptoms of DMI were
      unrecognizable at the start of treatment, which may be attributed to a lack of
      awareness of this rare condition among non-endocrinologist physicians. 

PMID- 24881755
TI  - Successful ablation of a unique left-sided accessory pathway.

PMID- 24881756
TI  - Double magenblase?

PMID- 24881757
TI  - Relationship between the red cell distribution width and one-year outcomes in
      chinese patients with stable angina pectoris.

PMID- 24881758
TI  - Response 1: relationship between the red cell distribution width and one-year
      outcomes in patients with stable angina pectoris in a Chinese population.

PMID- 24881759
TI  - Red cell distribution width in patients with coronary artery disease.

PMID- 24881760
TI  - Response 2: relationship between the red cell distribution width and one-year
      outcomes in patients with stable angina pectoris in a Chinese population.

PMID- 24881764
TI  - How to train your dragon: targeted delivery of microRNA to cancer cells in vivo.

PMID- 24881765
TI  - Are we done monkeying around with TRIM5alpha?

PMID- 24881766
TI  - Boolean immunotherapy: reversal of fortune.

PMID- 24881767
TI  - Raspberry-shaped composite microgel synthesis by seeded emulsion polymerization
      with hydrogel particles.
AB  - A series of raspberry-shaped composite microgels were synthesized by the seeded
      emulsion polymerization of styrene with hydrogel particles. Thermoresponsive
      microgels of poly(N-isopropylacrylamide) cross-linked with N,N'
      methylenebis(acrylamide) acted as cores for the polymerization. During the
      surfactant-free polymerization, the core microgels shrank at 70  degrees C to
      provide thermoresponsive composite microgels, and the polystyrene particles
      attached to core microgels became bigger with increasing styrene concentration.
      Conversely, composite microgels synthesized with sodium dodecyl sulfate (SDS)
      ([SDS] > 6.5 mM) did not exhibit thermoresponsive deswelling behavior because
      polystyrene particles covered the core microgels. In particular, polystyrene
      particles formed composites on the microgel surface as well as inside the
      microgels when the SDS concentration exceeded a critical value for core microgel
      swelling at 70  degrees C. A mechanism is proposed based on these results for the
      seeded emulsion polymerization of water-immiscible monomers with microgels. 

PMID- 24881769
TI  - Oleochemical industry future through biotechnology.
AB  - Lipases are the most widely used class of enzymes in organic synthesis. Enzymatic
      processes have been implemented in a broad range of industries as they are
      specific, save raw materials, energy and chemicals, environmentally friendly and
      fast in action compared to conventional processes. The most notable benefit is
      the moderate process temperature and pressure with no unwanted side reactions. In
      the past two decades, intensive research was carried out towards enzymatic
      synthesis of oleochemicals. This review has a sharp focus on the current
      implemented enzymatic processes for producing different oleochemicals such as
      fatty acids, glycerin, biodiesel, biolubricant and different alkyl esters via
      different processes including hydrolysis, esterification, transesterification and
      intraesterification. 

PMID- 24881768
TI  - New risk markers for cardiovascular prevention.
AB  - The importance of total cardiovascular (CV) risk estimation before management
      decisions are taken is well established. Models have been developed that allow
      physicians to stratify the asymptomatic population in subgroups at low, moderate,
      high, and very high total CV risk. Most models are based on classical CV risk
      factors: age, gender, smoking, blood pressure, and lipid levels. The impact of
      additional risk factors is discussed here, looking separately at the predictive
      increments of novel biomarkers and of indicators of subclinical atherosclerotic
      disease. The contribution of biomarkers to the total CV risk estimation is
      generally modest, and their usage should be limited to subjects at intermediate
      total CV risk. Detection of subclinical vascular damage may improve total CV risk
      estimation in asymptomatic subjects who are close to a threshold that could
      affect management decisions and in whom the chances of re-classification in a
      different risk category are great. There is, however, an urgent need for trials
      in which the value of using total CV risk estimation models is tested. 

PMID- 24881770
TI  - Characterization of volatile components and odor-active compounds in the oil of
      edible mushroom Boletopsis leucomelas.
AB  - The volatile oil from Boletopsis leucomelas (Pers.) Fayod was extracted by
      hydrodistillation with diethylether, and the volatile components of the oil were
      analyzed by gas chromatography-mass spectrometry. The oil contained 86
      components, representing 87.5% of the total oil. The main components of the oil
      were linoleic acid (15.0%), phenylacetaldehyde (11.2%), and palmitic acid (9.4%).
      Furthermore, sulfur-containing compounds including 3-thiophenecarboxaldehyde, 2
      acetylthiazole, S-methyl methanethiosulfonate, and benzothiazole were detected
      using gas chromatography-pulsed flame photometric detection. The odor components
      were evaluated by the odor activity value, and aroma extract dilution analysis
      was performed through gas chromatography-olfactometry analysis. The oil had a
      mushroom-like, fatty, and burnt odor. The main components contributing to the
      mushroom-like and fatty odor were hexanal, nonanal, 1-octen-3-ol, and (2E)
      nonenal, while the burnt odor was due to furfuryl alcohol, benzaldehyde, 5-methyl
      furfural, 2,3,5-trimethylpyrazine, 2-acethylthiazole, and indole. 

PMID- 24881771
TI  - Essential oils and crude extracts from Chrysanthemum trifurcatum leaves, stems
      and roots: chemical composition and antibacterial activity.
AB  - The essential oils from the leaves, stems and roots of Chrysanthemum trifurcatum
      (Desf.) Batt. and Trab. var. macrocephalum (viv.) were obtained by
      hydrodistillation and their chemical compositions were analysed by gas
      chromatography (GC) and gas chromatography-mass spectrometry (GC-MS), in order to
      get insight into similarities and differences as to their active composition. A
      total of fifty compounds were identified, constituting 97.84%, 99.02% and 98.20%
      of total oil composition of the leaves, stems and roots, respectively.
      Monoterpene hydrocarbons were shown to be the main group of constituents of the
      leaves and stems parts in the ratio of 67.88% and 51.29%, respectively. But, the
      major group in the roots oil was found to be sesquiterpene hydrocarbons (70.30%).
      The main compounds in leaves oil were limonene (26.83%), gamma-terpinene
      (19.68%), alpha-pinene (9.7%) and alpha-terpenyl acetate (7.16%). The stems oil,
      contains mainly limonene (32.91%), 4-terpenyl acetate (16.33%) and gamma
      terpinene (5.93%), whereas the main compounds in roots oil were alpha-calacorene
      (25.98%), alpha-cedrene (16.55%), beta-bourbobene (14.91%), elemol (7.45%) and 2
      hexenal (6.88%). The crude organic extracts of leaves, stems and roots, obtained
      by maceration with solvents of increasing polarity: petroleum ether, ethyl
      acetate and methanol, contained tannins, flavonoids and alkaloids. Meanwhile,
      essential oils and organic extracts were tested for antibacterial activities
      against eight Gram-positive and Gram-negative strains, using a microdilution
      method. The oil and methanolic extact from C. trifurcatum leaves showed a great
      potential of antibacterial effect against Bacillus subtilis and Staphylococcus
      epidermidis, with an IC50 range of 31.25-62.5 ug/ml. 

PMID- 24881772
TI  - Pachira glabra Pasq. essential oil: chemical constituents, antimicrobial and
      insecticidal activities.
AB  - The chemical composition of essential oil obtained by hydrodistillation of the
      leaves of Pachira glabra Pasq., (PgEO) has been studied by Gas Chromatography
      (GC) and Gas Chromatography coupled with Mass Spectrometry (GC/MS). Thirty three
      constituents representing 98.4% of total contents were identified from the
      essential oil. The major constituents of oil were limonene (23.2%), beta
      caryophyllene (14.5%), phtyol (8.5%) and beta-bisabolene (6.3%). The
      antimicrobial activity of the PgEO was evaluated against a panel of ten bacteria
      and three fungal strain using agar diffusion and broth microdilution methods.
      Results have shown that the PgEO exhibited moderate to strong antimicrobial
      activity against the tested microorganisms except Citrobacter youagae,
      Micrococcus spp. and Proteus spp. The activity zones of inhibition (ZI) and
      minimum inhibitory concentrations (MIC) ranged between 13.7 mm-24.0 mm and 0.3
      mg/mL-2.5 mg/mL, respectively. The insecticidal activity of PgEO was assayed
      against the adult Sitophilus zeamais. The lethal concentrations (LC50 and LC90)
      of the PgEO showed it to be toxic against adult S. zeamais at 32.2 and 53.7
      mg/mL, respectively. This is the first report on the chemical composition and in
      vitro biological activities of essential oil of P. glabra growing in Nigeria.

PMID- 24881773
TI  - Process parameters for operating 1-butanol gas stripping in a fermentor.
AB  - In this study, effects of the agitation speed, the flow rate, and type of non
      polar gases on the performance of gas stripping was systematically investigated.
      Macroscopically, the stripping rate of butanol is linearly proportional to the
      concentration of butanol in the feed solution. Nevertheless, a decrease in
      butanol selectivity was observed with the increasing butanol concentrations up to
      0.01 g/cm(3). This can be attributed to the thermodynamics reason that with
      increasing butanol concentrations in the feed, more stripping gas will dissolve
      in the feed solution that decrease the activity of butanol for mass transfer from
      liquids to gas bubbles. This can be supported by the use of highly soluble gas of
      carbon dioxide as the stripping gas where the Ksa dropped 48% compared to the
      nitrogen stripping. By the parameter sensitivity analysis, it has been shown that
      the dominant variable is the flow rate. The best strategy of maximizing the
      performance of 1-butanol gas stripping at a given flow rate is to bubble the
      gases at a high superficial velocity, which leads to a less resistance on the
      liquid side for mass transfer. 

PMID- 24881774
TI  - Re: Small solid renal masses: characterization by diffusion-weighted MRI at 3 T.

PMID- 24881776
TI  - Therapeutic exercise for prevention, treatment and rehabilitation of
      musculoskeletal pain and function as well as general health and life quality: a
      call for papers.

PMID- 24881775
TI  - Harnessing Hippo in the heart: Hippo/Yap signaling and applications to heart
      regeneration and rejuvenation.
AB  - The adult mammalian heart exhibits limited regenerative capacity after myocardial
      injury, a shortcoming that is responsible for the current lack of definitive
      treatments for heart failure. A search for approaches that might enhance adult
      heart regeneration has led to interest in the Hippo/Yap signaling pathway, a
      recently discovered signaling pathway that regulates cell proliferation and organ
      growth. Here we provide a brief overview of the Hippo/Yap pathway and its known
      roles in the developing and adult heart. We discuss the implications of Hippo/Yap
      signaling for regulation of cardiomyocyte death and regeneration. 

PMID- 24881777
TI  - Flexible ureteroscopy for renal stones.
AB  - OBJECTIVES: The objectives of this prospective study are to present our
      experience with retrograde intrarenal surgery (RIRS), and to analyze its results
      and complications. MATERIAL AND METHODS: 150 patients with renal stones were
      treated with RIRS. 111 cases showed single stones whilst multiple stones were
      observed in 39 cases. The mean size was 19.12mm (r: 5-74). Success rate was
      defined as the absence of residual stones or the presence of fragments <=2mm.
      RESULTS: in 21 (14%) patients RIRS could not be performed on first attempt
      because it was impossible to place the ureteral access sheath. The immediate
      success rate was 85.7%, and 91.6% at three months later. The average operating
      time was 85min (r: 25-220). Postoperative complications were observed in 22 cases
      (14.6%), although most of them were classified as Clavien 1 and 2 (19 cases), and
      only 2% (3 cases) showed Clavien 4 complications (sepsis requiring admission in
      the intensive care unit). 10 patients underwent a second procedure in order to
      complete the treatment. Thus, the number of procedures per patient was 1.06.
      There were no late complications. CONCLUSIONS: the treatment of renal stones with
      flexible ureteroscopy using the ureteral access sheath shows a high successful
      rate with a low complication rate. In order to define its indication more
      precisely, randomized studies comparing RIRS with minimally invasive percutaneous
      nephrolithotomy procedures (miniperc and microperc) would be necessary.

PMID- 24881779
TI  - Trends in pharmaceutical targeting of clinical indications: 1930-2013.
AB  - An analysis of FDA-approved new molecular entities (NMEs) reveals trends in
      therapeutic applications. Four groupings (infectious diseases, cardiovascular
      diseases, autoimmune/inflammatory diseases and cancer) capture more than 60% of
      NMEs. Infectious diseases are the most targeted indications. Near the turn of the
      new millennium, the rate of new approvals for infectious diseases decreased. The
      absolute and relative number of NMEs targeting psychiatric, neurological and
      pain/itch indications also declined. By contrast, NMEs targeting cancer have
      risen in the past two decades as have NMEs targeting orphan indications. These
      results suggest the drug development community has largely been responsive to
      public health and market needs. However, finite resources might indicate emphasis
      on some unmet needs could come at the cost of others. 

PMID- 24881778
TI  - Alginate encapsulation of human embryonic stem cells to enhance directed
      differentiation to pancreatic islet-like cells.
AB  - The pluripotent property of human embryonic stem cells (hESCs) makes them
      attractive for treatment of degenerative diseases such as diabetes. We have
      developed a stage-wise directed differentiation protocol to produce alginate
      encapsulated islet-like cells derived from hESCs, which can be directly implanted
      for diabetes therapy. The advantage of alginate encapsulation lies in its
      capability to immunoisolate, along with the added possibility of scalable
      culture. We have evaluated the possibility of encapsulating hESCs at different
      stages of differentiation. Encapsulation of predifferentiated cells resulted in
      insufficient cellular yield and differentiation. On the other hand, encapsulation
      of undifferentiated hESCs followed by differentiation induction upon
      encapsulation resulted in the highest viability and differentiation. More
      striking was that alginate encapsulation resulted in a much stronger
      differentiation compared to parallel two-dimensional cultures, resulting in 20
      fold increase in c-peptide protein synthesis. To elucidate the mechanism
      contributing to encapsulation-mediated enhancement in hESC maturation,
      investigation of the signaling pathways revealed interesting insight. While the
      phospho-protein levels of all the tested signaling molecules were lower under
      encapsulation, the ratio of pSMAD/pAKT was significantly higher, indicating a
      more efficient signal transduction under encapsulation. These results clearly
      demonstrate that alginate encapsulation of hESCs and differentiation to islet
      cell types provides a potentially translatable treatment option for type 1
      diabetes. 

PMID- 24881780
TI  - How do we measure pathology in PAH (lung and RV) and what does it tell us about
      the disease.
AB  - The current understanding of the pathology that underlies pulmonary vascular and
      right ventricular remodeling in pulmonary hypertension is discussed. Although
      recent studies underscored the importance of intima and media remodeling and, for
      the first time, the relevance of perivascular inflammation, much is needed to
      move the field forward. Reassessment of distribution and extension of the
      different vascular lesions requires state-of-the-art stereological tools, allied
      to three-dimensional casting and integration with data concerning cellular and
      molecular pathobiological processes. This integrated approach is ever more
      pressing in the right ventricle, because our understanding of key structural
      alterations of the failing right ventricle in pulmonary hypertension is lacking.
      This enterprise will enable better translation of pathogenetic processes to the
      human disease and provide key data to guide diagnostic and prognostic imaging
      approaches. 

PMID- 24881781
TI  - miRNAs in PAH: biomarker, therapeutic target or both?
AB  - Pulmonary arterial hypertension (PAH) is characterized by progressive increase in
      pulmonary vascular resistance leading to right ventricular hypertrophy and
      failure. There is a need to find new biomarkers to detect PAH at its early stages
      and also for new, more effective treatments for this disease. miRNAs have emerged
      as key players in cardiovascular diseases and cancer development and progression
      and, more recently, in PAH pathogenesis. In this review, we focus on the
      potential of miRNAs as biomarkers and new therapeutic targets for PAH. 

PMID- 24881782
TI  - Recombinant probiotics with antimicrobial peptides: a dual strategy to improve
      immune response in immunocompromised patients.
AB  - Bacterial infectious diseases are currently a serious health problem, especially
      in patients compromised by illness or those receiving immune-suppressant drugs.
      In this context, it is not only essential to improve the understanding of
      infectious mechanisms and host response but also to discover novel therapies with
      extreme urgency. Probiotics and antimicrobial peptides are also favorably viewed
      as novel strategies in the control of resistant bacteria. The present review will
      shed some light on the use of probiotic microorganisms expressing antimicrobial
      peptides as a dual therapy to control bacterial infectious diseases. 

PMID- 24881783
TI  - Tissue factor-fVIIa inhibition: update on an unfinished quest for a novel oral
      antithrombotic.
AB  - The tissue factor-coagulation factor VIIa complex (TF-fVIIa) is a well-validated
      biological target and has been the focus of extensive research directed toward
      the discovery of novel oral antithrombotics. This review briefly summarizes the
      key antithrombotic target validation data and provides an update on recent
      advances in small molecule TF-fVIIa inhibitors. 

PMID- 24881784
TI  - Brain vascular lesions: a clinicopathologic, immunohistochemistry, and
      ultrastructural approach.
AB  - Brain vascular malformations are relatively common lesions that cause serious
      neurologic disability or death in a significant proportion of individuals bearing
      them. The purpose of this study was to analyze the clinicopathologic and
      immunohistochemistry these lesions, looking for common antibodies expressed such
      as CD31, CD34, CD15, factor VIII, nestin, vimentin, vascular endothelial grow
      factor (VEGF), vascular endothelial grow factor receptor-2 (VEGF-R2), glial
      fibrillar acidic protien (GFAP), and fibroblastic grow factor beta (beta-FGF) and
      ultrastructure in endothelial cells as well as in vessel walls. Fifty cases of
      vascular lesions were included in this study: 29 (58%) of them were arteriovenous
      malformations and 21 (52%) were brain cavernomas. Twenty-six (52%) patients were
      women and 24 (48%) men. The age range was from 13 to 68 years (mean age, 35.86 +/
      15.19 years). The size of the lesions ranged between 1 and 8 cm (3 +/- 1.65 cm),
      and parieto-occipital lesions had a bigger size. Evolution time varied from 1
      month to 1 year (mean, 7.5 months). There was a significant statistical
      correlation between age and sex (P = -035), rupture of lesion (P = .015), brain
      hemorrhage (P = .033), necrosis (P = .011), hemosiderin deposit (P = .042), VEGF
      (P = .015), and VEGFR (P = .037), as well as localization of rupture (P = .017),
      loss of consciousness (P = .000), visual deficit (P = .026), hyaline vessels (P =
      .000), and CD31 (.009). Interactions between endothelial cells and mural cells
      (pericytes and vascular smooth muscle cells) in blood vessel walls have recently
      come into focus as central processes in the regulation of vascular formation,
      stabilization, remodeling, and function in brain vascular lesions. However, the
      molecular mechanisms that underlie the formation and growth of brain
      arteriovenous malformations are still poorly understood. 

PMID- 24881785
TI  - Sweet taste receptor expression in ruminant intestine and its activation by
      artificial sweeteners to regulate glucose absorption.
AB  - Absorption of glucose from the lumen of the intestine into enterocytes is
      accomplished by sodium-glucose co-transporter 1 (SGLT1). In the majority of
      mammalian species, expression (this includes activity) of SGLT1 is upregulated in
      response to increased dietary monosaccharides. This regulatory pathway is
      initiated by sensing of luminal sugar by the gut-expressed sweet taste receptor.
      The objectives of our studies were to determine (1) if the ruminant intestine
      expresses the sweet taste receptor, which consists of two subunits [taste 1
      receptor 2 (T1R2) and 3 (T1R3)], and other key signaling molecules required for
      SGLT1 upregulation in nonruminant intestines, and (2) whether T1R2-T1R3 sensing
      of artificial sweeteners induces release of glucagon-like peptide-2 (GLP-2) and
      enhances SGLT1 expression. We found that the small intestine of sheep and cattle
      express T1R2, T1R3, G-protein gustducin, and GLP-2 in enteroendocrine L-cells.
      Maintaining 110-d-old ruminating calves for 60d on a diet containing a starter
      concentrate and the artificial sweetener Sucram (consisting of saccharin and
      neohesperidin dihydrochalcone; Pancosma SA, Geneva, Switzerland) enhances (1)
      Na(+)-dependent d-glucose uptake by over 3-fold, (2) villus height and crypt
      depth by 1.4- and 1.2-fold, and (3) maltase- and alkaline phosphatase-specific
      activity by 1.5-fold compared to calves maintained on the same diet without
      Sucram. No statistically significant differences were observed for rates of
      intestinal glucose uptake, villus height, crypt depth, or enzyme activities
      between 50-d-old milk-fed calves and calves maintained on the same diet
      containing Sucram. When adult cows were kept on a diet containing 80:20 ryegrass
      hay-to-concentrate supplemented with Sucram, more than a 7-fold increase in SGLT1
      protein abundance was noted. Collectively, the data indicate that inclusion of
      this artificial sweetener enhances SGLT1 expression and mucosal growth in
      ruminant animals. Exposure of ruminant sheep intestinal segments to saccharin or
      neohesperidin dihydrochalcone evokes secretion of GLP-2, the gut hormone known to
      enhance intestinal glucose absorption and mucosal growth. Artificial sweeteners,
      such as Sucram, at small concentrations are potent activators of T1R2-T1R3 (600
      fold>glucose). This, combined with oral bioavailability of T1R2-T1R3 and the
      understanding that artificial sweetener-induced receptor activation evokes GLP-2
      release (thus leading to increased SGLT1 expression and mucosal growth), make
      this receptor a suitable target for dietary manipulation. 

PMID- 24881786
TI  - Lactobacillus helveticus SBT2171, a cheese starter, regulates proliferation and
      cytokine production of immune cells.
AB  - Consumption of a Lactobacillus helveticus SBT2171 (LH2171)-containing cheese has
      been reported to exhibit immunoregulatory actions, including an increase in
      regulatory T cell population and reduction in proinflammatory cytokine production
      in mice. We examined the in vitro effects of LH2171 cells per se on immune cell
      function, specifically proliferation and cytokine production, which are primary
      reactions of the immune response. Immune cell fractions were prepared by
      mechanical disruption of mesenteric lymph nodes (MLN), Peyer's patches (PP), and
      spleens (SP) of mice. The cell fractions were dispensed into a culture plate and
      stimulated with anti-CD3/CD28 antibody beads in place of antigen-presenting cells
      or lipopolysaccharide (LPS) in the presence or absence of heat-treated LH2171
      cells and other bacterial strains for comparison. After incubation,
      proliferation, cytokine production, and cell viability of the immune cells were
      determined. The LH2171 significantly inhibited the proliferation of MLN immune
      cells stimulated with anti-CD3/CD28 compared with other bacterial strains. The
      antiproliferative potency of LH2171 was effective not only on MLN but also on PP
      and SP stimulated with anti-CD3/CD28 or LPS. The LH2171 also decreased LPS
      stimulated IL-6 production from MLN, PP, and SP, and IL-1beta production from SP,
      but LH2171 did not affect the viability of immune cells. The LH2171 inhibited
      immune cell proliferation and proinflammatory cytokine (IL-6 and IL-1beta)
      production. The inhibitory actions were not due to cytotoxicity to immune cells,
      suggesting that LH2171 is a dairy Lactobacillus strain with beneficial
      immunoregulatory properties. 

PMID- 24881787
TI  - Continuous low-dose infusion of tumor necrosis factor alpha in adipose tissue
      elevates adipose tissue interleukin 10 abundance and fails to alter metabolism in
      lactating dairy cows.
AB  - Repeated bolus doses of tumor necrosis factor-alpha (TNFalpha) alters systemic
      metabolism in lactating cows, but whether chronic release of inflammatory
      cytokines from adipose tissue has similar effects is unclear. Late-lactation
      Holstein cows (n=9-10/treatment) were used to evaluate the effects of continuous
      adipose tissue TNFalpha administration on glucose and fatty acid (FA) metabolism.
      Cows were blocked by feed intake and milk yield and randomly assigned within
      block to control or TNFalpha treatments. Treatments (4mL of saline or 14ug/kg of
      TNFalpha in 4mL of saline) were infused continuously over 7d via 2 osmotic pumps
      implanted in a subcutaneous adipose depot. Plasma, milk samples, milk yield, and
      feed intake data were collected daily, and plasma glucose turnover rate was
      measured on d 7. At the end of d 7, pumps were removed and liver and
      contralateral tail-head adipose biopsies were collected. Results were modeled
      with the fixed effect of treatment and the random effect of block. Treatment with
      TNFalpha increased plasma concentrations of the acute phase protein haptoglobin,
      but did not alter plasma TNFalpha, IL-4, IL-6, or IFN-gamma concentrations, feed
      intake, or rectal temperature. Milk yield and composition were unchanged, and
      treatments did not alter the proportion of short- versus long-chain FA in milk on
      d 7. Treatments did not alter plasma free FA concentration, liver triglyceride
      content, or plasma glucose turnover rate. Surprisingly, TNFalpha infusion tended
      to decrease liver TNFalpha and IL-1 receptor 1 mRNA abundance and significantly
      increased adipose tissue IL-10 protein concentration. Continuous infusion of
      TNFalpha did not induce the metabolic responses previously observed following
      bolus doses delivered at the same rate per day. Metabolic homeostasis may have
      been protected by an adaptive anti-inflammatory response to control systemic
      inflammation. 

PMID- 24881788
TI  - Does iodine supplementation of the prepartum dairy cow diet affect serum
      immunoglobulin G concentration, iodine, and health status of the calf?
AB  - Absorption of adequate IgG from colostrum is critical to provide the newborn calf
      with adequate immunological protection and resistance to disease. Excessive
      iodine supplementation of the prepartum ewe reduces IgG absorption of her
      offspring; it is possible that excessive iodine supplementation of the prepartum
      dairy cow may similarly impair the ability of the calf to acquire immunological
      protection. The objectives of this study were to determine whether the iodine
      status, health status, and ability of calves to absorb IgG from colostrum were
      affected by prepartum iodine supplementation strategies of their dams. Dairy cows
      (n=127) received one of the following levels of iodine supplementation
      precalving: 15mg of iodine/kg of dietary dry matter (DM) (HI); no additional
      iodine supplementation (MI); 5mg/kg of dietary DM (SI); and 15mg of iodine/kg of
      DM for the first 3.5wk of the precalving period and no additional supplementation
      for the second 3.5wk (HMI). Calves were assigned to 1 of 6 experimental
      treatments, based on the prepartum iodine supplementation treatment of their dam
      and the precalving treatment group of the cows from which the colostrum fed was
      obtained: (1) HI_HI: born to HI dams, fed HI colostrum (i.e., colostrum produced
      by cows in the HI group); (2) MI_MI: born to MI dams, fed MI colostrum; (3)
      SI_SI: born to SI dams, fed SI colostrum; (4) HI_MI: born to HI dams, fed MI
      colostrum; (5) MI_HI: born to MI dams, fed HI colostrum; and (6) HMI_HMI: born to
      HMI dams, fed HMI colostrum. Concentration of calf serum IgG and plasma inorganic
      iodine (PII) was measured at 0 and 24h of age. Apparent efficiency of absorption
      for IgG was determined. Health scores were assigned to calves twice weekly and
      all episodes of disease were recorded. Cow experimental treatment group affected
      calf PII at 0h of age; the PII of calves born to HI dams (987.2ug/L) was greater
      than that of calves born to MI dams (510.1ug/L), SI (585.2ug/L), and HMI dams
      (692.9ug/L). Calf experimental treatment group affected calf PII at 24h of age;
      the PII of HI_HI (1,259.2ug/L) and HI_MI (1,177.8ug/L) calves was greater than
      MI_MI (240.7ug/L), SI_SI (302.2ug/L), HMI_HMI (320.7ug/L), and MI_HI (216.3ug/L)
      calves. No effect of experimental treatment was observed on the concentration of
      IgG measured in calf serum at 24h of age, or on apparent efficiency of
      absorption. Experimental treatment had no effect on the likelihood of a calf
      being assigned a worse nasal, eye and ear, cough, or fecal score within the study
      period, nor did it affect the probability of a calf receiving treatment for a
      disease a greater number of times. Prepartum iodine supplementation of cows at
      15mg/kg of DM increased the iodine levels in their calves at birth and 24h of
      age, but did not affect their ability to absorb IgG from colostrum.
      Supplementation with iodine above the minimum requirements established by the
      National Research Council was unnecessary to ensure appropriate iodine levels in
      calves at birth. 

PMID- 24881789
TI  - A dose-response evaluation of rumen-protected niacin in thermoneutral or heat
      stressed lactating Holstein cows.
AB  - Twenty-four multiparous high-producing dairy cows (40.0+/-1.4kg/d) were used in a
      factorial design to evaluate effects of 2 environments [thermoneutral (TN) and
      heat stress (HS)] and a dose range of dietary rumen-protected niacin (RPN; 0, 4,
      8, or 12g/d) on body temperature, sweating rate, feed intake, water intake,
      production parameters, and blood niacin concentrations. Temperature-humidity
      index values during TN never exceeded 68 (stress threshold), whereas temperature
      humidity index values during HS were above 68 for 24h/d. The HS environment
      increased hair coat and skin, rectal, and vaginal temperatures; respiration rate;
      skin and hair coat evaporative heat loss; and water intake and decreased DMI
      (3.5kg/d), milk yield (4.1kg/d), 4% fat-corrected milk (2.7kg/d), and milk
      protein yield (181.7g/d). Sweating rate increased during HS (12.7g/m(2) per h)
      compared with TN, but this increase was only 10% of that reported in summer
      acclimated cattle. Niacin supplementation did not affect sweating rate, dry
      matter intake, or milk yield in either environment. Rumen-protected niacin
      increased plasma and milk niacin concentrations in a linear manner. Heat stress
      reduced niacin concentration in whole blood (7.86 vs. 6.89MUg/mL) but not in
      milk. Reduced blood niacin concentration was partially corrected by dietary RPN.
      An interaction existed between dietary RPN and environment; dietary RPN linearly
      increased water intake in both environments, but the increase was greater during
      HS conditions. Increasing dietary RPN did not influence skin temperatures. During
      TN, supplementing 12g/d of RPN increased hair coat (unshaved skin; 30.3 vs. 31.3
      degrees C at 1600h) but not shaved skin (32.8 vs. 32.9 degrees C at 1600h)
      temperature when compared with 0g/d at all time points, whereas the maximum
      temperature (18 degrees C) of the room was lower than skin temperature. These
      data suggest that dietary RPN increased water intake during both TN and HS and
      hair coat temperature during TN; however, core body temperature was unaffected.
      Thus, encapsulated niacin did not improve thermotolerance of winter-acclimated
      lactating dairy cows exposed to moderate thermal stress in Arizona. 

PMID- 24881790
TI  - Utilization of temporal dominance of sensations and time intensity methodology
      for development of low-sodium Mozzarella cheese using a mixture of salts.
AB  - Evidence has linked excessive salt consumption to the development of chronic
      degenerative diseases. Therefore, special attention has been given to the
      consumption of healthier products with reduced sodium contents. This study aimed
      to develop a Mozzarella cheese with a reduced sodium content using a mixture of
      salts through acceptance testing and temporal sensory evaluation. The following 3
      formulations of Mozzarella cheese were prepared: formulation A (control), which
      was produced only with NaCl (0% sodium reduction), formulation B (30% sodium
      reduction), and formulation C (54% sodium reduction). Every formulation was
      produced using a mixture of salts consisting of NaCl, KCl, and monosodium
      glutamate at different concentrations. The products underwent sensory acceptance
      tests, and the time intensity and temporal dominance of sensations were
      evaluated. The proportions of salts used did not cause strange or bad tastes but
      did result in lower intensities of saltiness. Mozzarella with low sodium content
      (B and C) had a sensory acceptance similar to that of traditional Mozzarella (A).
      Therefore, the use of a mixture of salts consisting of NaCl, KCl, and monosodium
      glutamate is a viable alternative for the production of Mozzarella, with up to a
      54% reduction in the sodium content while still maintaining acceptable sensory
      quality. 

PMID- 24881792
TI  - Methods to determine the relative value of genetic traits in dairy cows to reduce
      greenhouse gas emissions along the chain.
AB  - Current decisions on breeding in dairy farming are mainly based on economic
      values of heritable traits, as earning an income is a primary objective of
      farmers. Recent literature, however, shows that breeding also has potential to
      reduce greenhouse gas (GHG) emissions. The objective of this paper was to compare
      2 methods to determine GHG values of genetic traits. Method 1 calculates GHG
      values using the current strategy (i.e., maximizing labor income), whereas method
      2 is based on minimizing GHG per kilogram of milk and shows what can be achieved
      if the breeding results are fully directed at minimizing GHG emissions. A whole
      farm optimization model was used to determine results before and after 1 genetic
      standard deviation improvement (i.e., unit change) of milk yield and longevity.
      The objective function of the model differed between method 1 and 2. Method 1
      maximizes labor income; method 2 minimizes GHG emissions per kilogram of milk
      while maintaining labor income and total milk production at least at the level
      before the change in trait. Results show that the full potential of the traits to
      reduce GHG emissions given the boundaries that were set for income and milk
      production (453 and 441kg of CO2 equivalents/unit change per cow per year for
      milk yield and longevity, respectively) is about twice as high as the reduction
      based on maximizing labor income (247 and 210kg of CO2 equivalents/unit change
      per cow per year for milk yield and longevity, respectively). The GHG value of
      milk yield is higher than that of longevity, especially when the focus is on
      maximizing labor income. Based on a sensitivity analysis, it was shown that
      including emissions from land use change and using different methods for handling
      the interaction between milk and meat production can change results, generally in
      favor of milk yield. Results can be used by breeding organizations that want to
      include GHG values in their breeding goal. To verify GHG values, the effect of
      prices and emissions factors should be considered, as well as the potential
      effect of variation between farm types. 

PMID- 24881793
TI  - Farm characteristics and calf management practices on dairy farms with and
      without diarrhea: a case-control study to investigate risk factors for calf
      diarrhea.
AB  - Calf diarrhea is one of the most important problems in calf rearing on dairy
      farms worldwide. Besides pathogens, several noninfectious management factors,
      especially management around birth, colostrum management, calf housing, feeding,
      and hygiene are important in the pathogenesis of diarrhea. To date, few data are
      available concerning calf rearing management on small and medium-sized dairy
      farms that are typical for Austria and the alpine region. Consequently, the
      objectives of this case-control study were to evaluate routine calf management
      practices on Austrian dairy farms and to examine differences in management
      between farms with and without the presence of calf diarrhea to identify risk
      factors. Overall, 100 dairy farms were visited. Of these farms, 50 were chosen
      based on the history and presence of calf diarrhea (case farms). Another 50 farms
      with no presence of calf diarrhea were chosen to serve as a standard of
      comparison (control farms). On farms, management was evaluated by face-to-face
      interview, and health status and hygiene were surveyed. Several calf rearing
      management procedures were similar on all of the visited farms, especially in
      areas regulated by national and European law. These factors include colostrum
      management and feeding. Consequently, no influence of these factors on the
      appearance of calf diarrhea could be detected. In contrast, other areas such as
      hygiene measures differed between farms and showed a partial association with the
      presence of calf diarrhea on farm. Variables related to diarrhea on farm were
      farm size; that is, the number of cows on farm. Farms with diarrhea cases were
      larger (median 40 cows, interquartile range 24.5 to 64.0) compared with farms
      with no presence of diarrhea (median 28 cows, interquartile range 18.8 to 44.0).
      Other risk factors that influenced the presence of diarrhea were the presence of
      other farm animal species on the farm [odds ratio (OR) 26.89, 95% confidence
      interval (CI): 2.64 to 273.5], frequency of cleaning of the calving area (OR
      0.12, 95% CI: 0.02 to 0.79), the placement of individual calf housings (barn vs.
      outdoors; OR 0.02, 95% CI: 0.00 to 0.47), and the presence of respiratory tract
      disease (OR 52.49, 95% CI: 1.26 to 2,181.83). The possible influence of these
      factors on the appearance of calf diarrhea should be considered when farmers are
      advised. 

PMID- 24881791
TI  - Effects of feed restriction and prolactin-release inhibition at drying off on
      metabolism and mammary gland involution in cows.
AB  - A cow's risk of acquiring a new intramammary infection during the dry period
      increases with milk production at drying off and decreases as mammary gland
      involution progresses. A method commonly used to reduce milk production is a
      drastic reduction in feed supply in the days that precede drying off. Milk
      production can also be reduced by inhibiting the lactogenic signal driven by
      prolactin (PRL). This study aimed to compare the effects of these 2drying-off
      procedures on metabolism, immunity, and mammary gland involution in cows. A total
      of 24Holstein cows in late lactation were assigned to 1 of 3treatments based on
      milk yield, somatic cell count, and parity. The cows were fed a lactation diet
      until drying off (control; n=8), only dry hay during the last 5d before drying
      off (DH; n=8), or the same lactation diet as the control cows but with twice
      daily i.m. injections of 4mg of quinagolide, a specific inhibitor of PRL release,
      from 5d before drying off until 13d after (QN; n=8). Quinagolide induced a
      decrease in PRL concentration in blood and in milk and mammary secretions on all
      the injection days. Interestingly, PRL was also depressed in the blood and milk
      of the hay-fed cows before drying off. Both the QN and DH treatments induced a
      decrease in milk production, which averaged 17.9 and 10.1kg/d for the QN and DH
      cows, respectively, at drying off in comparison with 24.8kg/d for the control
      cows. Both BSA concentration and Na(+)-to-K(+) ratio increased faster in the
      mammary secretions of both the DH and QN cows than in those of the control cows,
      whereas citrate-to-lactoferrin ratio, another indicator of involution rate,
      decreased faster. The DH treatment decreased blood concentrations of glucose and
      most amino acids and increased blood concentrations of beta-hydroxybutyrate and
      nonesterified fatty acids. Quinagolide increased blood glucose but did not affect
      the other metabolites. The serum harvested on d-1 from the hay-fed cows reduced
      peripheral blood mononuclear cell proliferation and IL-4 production, whereas the
      serum from the quinagolide-treated cows had no effect. In conclusion, this
      experiment shows that PRL-release inhibition could be a new alternative for
      reducing milk production before drying off and for hastening mammary gland
      involution without disturbing the metabolism of the cow. 

PMID- 24881794
TI  - A physicochemical investigation of membrane fouling in cold microfiltration of
      skim milk.
AB  - The main challenge in microfiltration (MF) is membrane fouling, which leads to a
      significant decline in permeate flux and a change in membrane selectivity over
      time. This work aims to elucidate the mechanisms of membrane fouling in cold MF
      of skim milk by identifying and quantifying the proteins and minerals involved in
      external and internal membrane fouling. Microfiltration was conducted using a 1.4
      MUm ceramic membrane, at a temperature of 6+/-1 degrees C, cross-flow velocity of
      6m/s, and transmembrane pressure of 159kPa, for 90min. Internal and external
      foulants were extracted from a ceramic membrane both after a brief contact
      between the membrane and skim milk, to evaluate instantaneous adsorption of
      foulants, and after MF. Four foulant streams were collected: weakly attached
      external foulants, weakly attached internal foulants, strongly attached external
      foulants, and strongly attached internal foulants. Liquid chromatography coupled
      with tandem mass spectrometry analysis showed that all major milk proteins were
      present in all foulant streams. Proteins did appear to be the major cause of
      membrane fouling. Proteomics analysis of the foulants indicated elevated levels
      of serum proteins as compared with milk in the foulant fractions collected from
      the adsorption study. Caseins were preferentially introduced into the fouling
      layer during MF, when transmembrane pressure was applied, as confirmed both by
      proteomics and mineral analyses. The knowledge generated in this study advances
      the understanding of fouling mechanisms in cold MF of skim milk and can be used
      to identify solutions for minimizing membrane fouling and increasing the
      efficiency of milk MF. 

PMID- 24881795
TI  - Short communication: Staphylococcus aureus isolated from colostrum of dairy
      heifers represent a closely related group exhibiting highly homogeneous genomic
      and antimicrobial resistance features.
AB  - In heifers, intramammary infections caused by Staphylococcus aureus affect milk
      production and udder health in the first and subsequent lactations, and can lead
      to premature culling. Not much is known about Staph. aureus isolated from heifers
      and it is also unclear whether or not these strains are readily transmitted
      between heifers and lactating herd mates. In this study, we compared phenotypic
      characteristics, spa types, and DNA microarray virulence and resistance gene
      profiles of Staph. aureus isolates obtained from colostrum samples of dairy
      heifers with isolates obtained from lactating cows. Our objective was to (1)
      characterize Staph. aureus strains associated with mastitis in heifers and (2)
      determine relatedness of Staph. aureus strains from heifers and lactating cows to
      provide data on transmission. We analyzed colostrum samples of 501 heifers and
      milk samples of 68 lactating cows within the same herd, isolating 48 and 9 Staph.
      aureus isolates, respectively. Staphylococcus aureus strains from heifers,
      lactating herd mates, and an unrelated collection of 78 strains from bovine
      mastitis milk of mature cows were compared. With 1 exception each,
      characterization of all strains from heifers and lactating cows in the same herd
      yielded highly similar phenotypic and genotypic results. The strains were
      Staphaurex latex agglutination test negative (Oxoid AG, Basel, Switzerland) and
      belonged to agr type II, CC705, and spa types tbl 2645 and t12926. They were
      susceptible to all antimicrobial agents tested. In contrast, the strains from
      mature cows in other herds were spread across different clonal complexes, spa
      types, and SplitsTree clusters (http://www.splitstree.org/), thus displaying a
      far higher degree of heterogeneity. We conclude that strains isolated from
      colostrum of heifers and mastitis milk of lactating cows in the same herd feature
      highly similar phenotypic and genomic characteristics, suggesting persistence of
      the organism during the first and potentially subsequent lactations or
      transmission between heifers and mature herd mates. 

PMID- 24881796
TI  - Short communication: biofilm production characterization of mecA and mecC
      methicillin-resistant Staphylococcus aureus isolated from bovine milk in Great
      Britain.
AB  - Staphylococcus aureus is an important cause of contagious intramammary infection
      in dairy cattle, and the ability to produce biofilm is considered to be an
      important virulence property in the pathogenesis of mastitis. The aim of this
      study was to characterize the biofilm formation capacity of methicillin-resistant
      Staph. aureus (MRSA), encoding mecA or mecC, isolated from bulk tank milk in
      Great Britain. For this purpose, 20 MRSA isolates were grown on microtiter plates
      to determine the biofilm production. Moreover, the spa-typing and the presence of
      the intercellular adhesion genes icaA and icaD were analyzed by PCR. All MRSA
      isolates tested belonged to 9 spa-types and were PCR-positive for the ica genes;
      10 of them (50%) produced biofilm in the microtiter plate assay. This is also the
      first demonstration of biofilm production by mecC MRSA. 

PMID- 24881797
TI  - Efficacy of vaccination on Staphylococcus aureus and coagulase-negative
      staphylococci intramammary infection dynamics in 2 dairy herds.
AB  - The aim of this study was to evaluate vaccine efficacy of a commercial vaccine
      (Startvac, Hipra Spain) aimed at reducing intramammary infections (IMI) with
      Staphylococcus aureus and coagulase-negative staphylococci under field
      conditions. During the 21-mo duration of the study, 1,156 lactations from 809
      cows were enrolled in 2 herds. During the first phase of the trial, all cows that
      were due to calve were vaccinated until approximately 50% of cows in the milking
      herd were vaccinated (at ~6mo). At that point, when 50% vaccination coverage was
      reached, cows that were due to calve were randomly assigned to be vaccinated or
      left as negative controls. Cure rate, rate of new infection, prevalence, and
      duration of infections were analyzed. Vaccination resulted in a moderate
      reduction in incidence of new staphylococcal IMI and a more pronounced reduction
      in duration of IMI associated with reduction of the basic reproduction ratio of
      Staph. aureus by approximately 45% and of coagulase-negative staphylococci by
      approximately 35%. The utilization of vaccine in combination with other infection
      control procedures, such as excellent milking procedures, treatment, segregation,
      and culling of known infected cattle, will result in an important reduction in
      incidence and duration of intramammary staphylococcal infections. 

PMID- 24881798
TI  - A longitudinal study of feed contamination by European starling excreta in Ohio
      dairy farms (2007-2008).
AB  - The objectives of this study were to understand the temporal pattern of
      contamination of cattle feed by starling excrement on dairy farms and to evaluate
      the temporal pattern in recovering Escherichia coli O157:H7 or Salmonella in
      relation to the absolute mass of excrement recovered. A longitudinal study was
      conducted on 15 dairy farms in Ohio from July 2007 to October 2008. One open
      topped tray filled with bird feed was placed near a cattle feeding site; bird
      excrement from the tray was weighed monthly for 12 consecutive months. Linear
      regression models with a random intercept for farm were computed to examine the
      association between the absolute weight of excrement recovered each month or the
      farm-specific standard score for weight of excrement, and month or season. Exact
      logistic regression was used to determine whether an association between
      recovering E. coli O157:H7 or Salmonella was present and the amount of excrement
      recovered and season. A spatial scan statistic was used to test for evidence of
      space-time clustering of excrement, based on the standard score for the weight of
      the excrement, among our study farms. A total of 5 of 179 excrement samples
      (2.79%) were positive for E. coli O157:H7 and 2 (1.12%) were positive for
      Salmonella. A significantly higher level of contamination with excrement was
      observed during the winter. The odds of recovering a pathogen increased with the
      amount of excrement recovered and decreased if the excrement was collected in the
      winter. A spatio-temporal cluster of contamination with excrement was detected.
      These findings provide basic information for future quantitative microbial risk
      assessments concerning the role of starlings in spreading enteric pathogens on
      dairy farms. 

PMID- 24881799
TI  - Effect of recombinant bovine granulocyte colony-stimulating factor covalently
      bound to polyethylene glycol injection on neutrophil number and function in
      periparturient dairy cows.
AB  - Dairy cows often experience decreased immune function around the time of calving,
      typified by impaired polymorphonuclear neutrophil (PMN) function and a transient
      neutropenia. This is associated with increased disease incidence, including
      mastitis, retained placenta, and metritis. In an attempt to improve PMN
      functional capacity during the periparturient period, we injected cows with
      recombinant bovine granulocyte colony-stimulating factor covalently bound to
      polyethylene glycol (PEG rbG-CSF) twice subcutaneously, about 6d before calving
      and within 24h after calving. Twenty-one cows in their second pregnancy were
      enrolled in this study and divided into 2 groups: PEG rbG-CSF treated (n=11) and
      saline-treated controls (n=10). The PMN numbers quickly and dramatically
      increased after PEG rbG-CSF administration and remained elevated through the end
      of the experiment (13d after calving). Exocytosis of myeloperoxidase by
      stimulated PMN, which is generally decreased in periparturient cows, was markedly
      increased by PEG rbG-CSF after injection. Higher myeloperoxidase exocytosis
      persisted for at least 10d after calving. The PMN superoxide anion release and
      phagocytosis activity did not differ between groups. Injection of PEG rbG-CSF was
      safe for cows, with no significant negative effects observed. The greatest single
      effect of PEG rbG-CSF administration was a dramatic increase in circulating
      numbers of PMN. The increased numbers of PMN ready to move to a site of infection
      early in the course of an infection may improve the ability of the cow to ward
      off clinical disease in the periparturient period. 

PMID- 24881800
TI  - Ruminal bacterial community shifts in grain-, sugar-, and histidine-challenged
      dairy heifers.
AB  - Ruminal bacterial community composition (BCC) and its associations with ruminal
      fermentation measures were studied in dairy heifers challenged with combinations
      of grain, fructose, and histidine in a partial factorial study. Holstein-Friesian
      heifers (n=30) were randomly allocated to 5 triticale grain-based treatment
      groups: (1) control (no grain), (2) grain [fed at a dry matter intake (DMI) of
      1.2% of body weight (BW)], (3) grain (0.8% of BW DMI) + fructose (0.4% of BW
      DMI), (4) grain (1.2% of BW DMI) + histidine (6g/head), and (5) grain (0.8% of BW
      DMI) + fructose (0.4% of BW DMI) + histidine (6g/head). Ruminal fluid was
      collected using a stomach tube 5, 115, and 215min after consumption of the
      rations and bacterial 16S ribosomal DNA sequence data was analyzed to
      characterize bacteria. Large variation among heifers and distinct BCC were
      evident in a between-group constrained principal components analysis. Bacterial
      composition in the fructose-fed heifers was positively related to total lactate
      and butyrate concentrations. Bacterial composition was positively associated with
      ruminal ammonia, valerate, and histamine concentrations in the grain-fed heifers.
      The predominant phyla were the Firmicutes (57.6% of total recovered sequences),
      Bacteroidetes (32.0%), and candidate phylum TM7 (4.0%). Prevotella was the
      dominant genus. In general, grain or histidine or their interactions with time
      had minimal effects on the relative abundance of bacterial phyla and families.
      Fructose increased and decreased the relative abundance of the Firmicutes and
      Proteobacteria phyla over time, respectively, and decreased the abundance of the
      Prevotellaceae family over time. The relative abundance of the Streptococcaceae
      and Veillonellaceae families was increased in the fructose-fed heifers and these
      heifers over time. A total of 31 operational taxonomic units differed among
      treatment groups in the 3.6h sampling period, Streptococcus bovis was observed in
      fructose fed animals. The TM7 candidate phylum had an increased abundance of
      sequence reads by over 2.5 fold due to the introduction of histidine into the
      diet. Rapid changes in BCC can occur in a short period after a single substrate
      challenge and the nature of these changes may influence ruminal acidosis risk and
      differ from those in cattle exposed to substrate challenges over a longer time
      period. 

PMID- 24881801
TI  - Genotype-specific risk factors for Staphylococcus aureus in Swiss dairy herds
      with an elevated yield-corrected herd somatic cell count.
AB  - Bovine mastitis is a frequent problem in Swiss dairy herds. One of the main
      pathogens causing significant economic loss is Staphylococcus aureus. Various
      Staph. aureus genotypes with different biological properties have been described.
      Genotype B (GTB) of Staph. aureus was identified as the most contagious and one
      of the most prevalent strains in Switzerland. The aim of this study was to
      identify risk factors associated with the herd-level presence of Staph. aureus
      GTB and Staph. aureus non-GTB in Swiss dairy herds with an elevated yield
      corrected herd somatic cell count (YCHSCC). One hundred dairy herds with a mean
      YCHSCC between 200,000 and 300,000cells/mL in 2010 were recruited and each farm
      was visited once during milking. A standardized protocol investigating
      demography, mastitis management, cow husbandry, milking system, and milking
      routine was completed during the visit. A bulk tank milk (BTM) sample was
      analyzed by real-time PCR for the presence of Staph. aureus GTB to classify the
      herds into 2 groups: Staph. aureus GTB-positive and Staph. aureus GTB-negative.
      Moreover, quarter milk samples were aseptically collected for bacteriological
      culture from cows with a somatic cell count >=150,000cells/mL on the last test
      day before the visit. The culture results allowed us to allocate the Staph.
      aureus GTB-negative farms to Staph. aureus non-GTB and Staph. aureus-free groups.
      Multivariable multinomial logistic regression models were built to identify risk
      factors associated with the herd-level presence of Staph. aureus GTB and Staph.
      aureus non-GTB. The prevalence of Staph. aureus GTB herds was 16% (n=16), whereas
      that of Staph. aureus non-GTB herds was 38% (n=38). Herds that sent lactating
      cows to seasonal communal pastures had significantly higher odds of being
      infected with Staph. aureus GTB (odds ratio: 10.2, 95% CI: 1.9-56.6), compared
      with herds without communal pasturing. Herds that purchased heifers had
      significantly higher odds of being infected with Staph. aureus GTB (rather than
      Staph. aureus non-GTB) compared with herds without purchase of heifers.
      Furthermore, herds that did not use udder ointment as supportive therapy for
      acute mastitis had significantly higher odds of being infected with Staph. aureus
      GTB (odds ratio: 8.5, 95% CI: 1.6-58.4) or Staph. aureus non-GTB (odds ratio:
      6.1, 95% CI: 1.3-27.8) than herds that used udder ointment occasionally or
      regularly. Herds in which the milker performed unrelated activities during
      milking had significantly higher odds of being infected with Staph. aureus GTB
      (rather than Staph. aureus non-GTB) compared with herds in which the milker did
      not perform unrelated activities at milking. Awareness of 4 potential risk
      factors identified in this study guides implementation of intervention strategies
      to improve udder health in both Staph. aureus GTB and Staph. aureus non-GTB
      herds. 

PMID- 24881802
TI  - Perceptual learning--the past, present and future.

PMID- 24881803
TI  - Needle-free jet injection for administration of influenza vaccine: a randomised
      non-inferiority trial.
AB  - BACKGROUND: Administration of vaccines by needle-free technology such as jet
      injection might offer an alternative to needles and syringes that avoids the
      issue of needle phobia and the risk of needle-stick injury. We aimed to assess
      the immunogenicity and safety of trivalent influenza vaccine given by needle-free
      jet injector compared with needle and syringe. METHODS: For this randomised,
      comparator-controlled trial, we randomly assigned (1:1) healthy adults (aged 18
      64 years) who attended one of four employee health clinics in the University of
      Colorado health system, with stratification by site, to receive one dose of the
      trivalent inactivated influenza vaccine Afluria given either intramuscularly with
      a needle-free jet injector (Stratis; PharmaJet, Golden, CO, USA) or with needle
      and syringe. Randomisation was done with a computer-generated randomisation
      schedule with a block size of 100. Because of the nature of the study, masking of
      participants was not possible. Immunogenicity was assessed by measurement of the
      hemagglutination inhibition antibody titres in serum for the three viral strains
      included in the vaccine. We included six coprimary endpoints: three strain
      specific geometric mean titre ratios and the absolute differences in three strain
      specific seroconversion rates. The immune response of the jet injector group was
      regarded as non-inferior to that of the needle and syringe group if both the
      upper bound of each of the three 95% CIs for the strain-specific geometric mean
      titre ratios was 1.5 or less, and the upper bound of the three 95% CIs for the
      strain-specific seroconversion rate differences was less than 10 percentage
      points. We used t test for group comparison. This study is registered with
      ClinicalTrials.gov, number NCT01688921. FINDINGS: During the 2012-13 influenza
      season of the northern hemisphere, we allocated 1250 participants to receive
      vaccination by needle-free jet injector (n=627) or needle and syringe (n=623). In
      the intention-to-treat immunogenicity population, all participants with two serum
      samples were included (575 in the jet injector group and 574 in the needle and
      syringe group). The immune response to Afluria when given by needle-free jet
      injector met the criteria for non-inferiority for all six coprimary endpoints.
      The jet injector group met the geometric mean titre criterion for non-inferiority
      for the A/H1N1, A/H3N2, and B strains (upper bound of the 95% CI for the
      geometric mean titre ratios were 1.10 for A/H1N1, 1.17 for A/H3N2, and 1.04 for B
      strains). The jet injector group met the seroconversion rate criterion for non
      inferiority for the A/H1N1, A/H3N2, and B strains (upper bound of the 95% CI of
      the seroconversion rate differences were 6.0% for A/H1N1, 7.0% for A/H3N2, and
      5.7% for B strains). We recorded serious adverse events in three participants,
      none of which were study related. INTERPRETATION: The immune response to
      influenza vaccine given with the jet injector device was non-inferior to the
      immune response to influenza vaccine given with needle and syringe. The device
      had a clinically acceptable safety profile, but was associated with a higher
      frequency of local injection site reactions than was the use of needle and
      syringe. The Stratis needle-free jet injector device could be used as an
      alternative method of administration of Afluria trivalent influenza vaccine.
      FUNDING: Biomedical Advanced Research and Development Authority (BARDA), PATH,
      bioCSL, and PharmaJet.

PMID- 24881804
TI  - Systemic lupus erythematosus.
AB  - Systemic lupus erythematosus is a remarkable and challenging disorder. Its
      diversity of clinical features is matched by the complexity of the factors
      (genetic, hormonal, and environmental) that cause it, and the array of
      autoantibodies with which it is associated. In this Seminar we reflect on changes
      in its classification criteria; consider aspects of its more serious clinical
      expression; and provide a brief review of its aetiopathogenesis, major
      complications, coping strategies, and conventional treatment. Increased
      understanding of the cells and molecules involved in the development of the
      diseases has encouraged the identification of new, better targeted biological
      approaches to its treatment. The precise role of these newer therapies remains to
      be established. 

PMID- 24881805
TI  - Effects of two weeks of cerebellar theta burst stimulation in cervical dystonia
      patients.
AB  - Dystonia is generally regarded as a disorder of the basal ganglia and their
      efferent connections to the thalamus and brainstem, but an important role of
      cerebellar-thalamo-cortical (CTC) circuits in the pathophysiology of dystonia has
      been invoked. Here in a sham controlled trial, we tested the effects of two-weeks
      of cerebellar continuous theta burst stimulation (cTBS) in a sample of cervical
      dystonia (CD) patients. Clinical evaluations were performed by administering the
      Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and the Burke-Fahn
      Marsden Dystonia Rating Scale (BFMDRS). We used TMS to measure the inhibitory
      connectivity between the cerebellum and the contralateral motor cortex
      (cerebellar brain inhibition [CBI]), and the excitability of the contralateral
      primary motor cortex assessing intracortical inhibition (SICI), intracortical
      facilitation (ICF) and cortical silent period (CSP). Paired associative
      stimulation (PAS) was tested to evaluate the level and the topographical
      specificity of cortical plasticity, which is abnormally enhanced and non-focal in
      CD patients. Two weeks of cerebellar stimulation resulted in a small but
      significant clinical improvement as measured by the TWSTRS of approximately 15%.
      Cerebellar stimulation modified the CBI circuits and reduced the heterotopic PAS
      potentiation, leading to a normal pattern of topographic specific induced
      plasticity. These data provide novel evidence CTC circuits could be a potential
      target to partially control some dystonic symptoms in patients with cervical
      dystonia.

PMID- 24881806
TI  - Effects of transcutaneous neuromodulation (TENS) on overactive bladder symptoms
      in children: a randomized controlled trial.
AB  - BACKGROUND: The aim of the present study was to investigate whether addition of
      transcutaneous electrical nerve stimulation (TENS) treatment improves the results
      of standard urotherapy in children with overactive bladder (OAB) symptoms.
      MATERIAL AND METHODS: Sixty-two children with symptoms of OAB and incontinence
      were included. The children were randomized either to standard urotherapy
      treatment alone or a combination of standard urotherapy and TENS. The effect
      variables were taken from a voiding-drinking diary: number of voiding, number of
      incontinence episodes, and maximum voided volume. RESULTS: Both treatment groups
      had good treatment results, with no significant difference between the groups. In
      the standard treatment group 13/28 (46%) were completely dry and 11/28 (40%) had
      a decrease in incontinence episodes, compared to 16/24 (67%) and 3/24 (13%),
      respectively, in the standard+TENS group (p=0.303). The number of voiding
      decreased in two-thirds of the patients in both groups. However, maximal voided
      volume only increased in the standard treatment group. Subjectively 72% and 80%
      considered themselves significantly improved or free of symptoms. Previous
      treatment was registered in 15/55 (27%). All efficacy variables decreased in
      those with previous treatment, but with no difference between the standard and
      standard+TENS treatment groups. The only difference noted was when comparing the
      children without previous treatment in the groups: a significantly higher
      proportion were completely dry in the TENS group (12/18 [71%] versus 10/22 [48%],
      p=0.05). CONCLUSION: Our results showed no significant difference overall in
      treatment response to OAB symptoms between urotherapy only and urotherapy+TENS,
      whereas a tendency to difference was found in children without previous
      treatment. Thus with good urotherapy support, TENS only seems to have marginal
      additional effects on OAB symptoms.

PMID- 24881807
TI  - Laparoscopic ureteral ligation (clipping): a novel, simple procedure for
      pediatric urinary incontinence due to ectopic ureters associated with non
      functioning upper pole renal moieties.
AB  - OBJECTIVE: A simplified approach for the surgical management of symptomatic
      ectopic ureters, associated with a non-functioning upper moiety, with
      laparoscopic ureteric clipping is presented in this research paper. MATERIALS AND
      METHODS: Prospectively collected data on nine consecutive girls with ectopic
      ureters associated with urinary incontinence who underwent laparoscopic clipping
      between February 2011 and December 2013. Surgical technique consisted of
      cystoscopy and insertion of ureteral catheter in the lower pole ureter to aid in
      identification and clipping of the ectopic ureter, which was achieved by standard
      trans-peritoneal laparoscopy. RESULTS: Median age was eight years (range 4-17
      years). Diagnosis was based on clinical findings, which were supported by:
      ultrasound (US), nuclear scans and magnetic resonance urography in Cases 9, 8 and
      5, respectively. Bilateral complete duplication was present in two patients; the
      combination of cystoscopy and laparoscopy allowed adequate identification of the
      ectopic ureter causing incontinence in both. All nine patients were immediately
      dry after surgery and remain asymptomatic after a maximum follow up of 27 months.
      Eight out of nine patients had developed some degree of asymptomatic upper pole
      hydronephrosis on follow-up US. CONCLUSION: Laparoscopic clipping holds promise
      as a simple alternative to other more-complex surgical procedures in the
      treatment of incontinence due to an ectopic ureter. Despite favorable and
      encouraging initial results, further follow up is warranted in order to determine
      the fate of expected associated upper-pole hydronephrosis.

PMID- 24881808
TI  - Characterization of phenolic compounds in Brazilian pepper (Schinus
      terebinthifolius Raddi) exocarp.
AB  - The objective of this study was to characterize the phenolic composition of
      Brazilian pepper (Schinus terebinthifolius Raddi) exocarp extract. Using UHPLC
      DAD-MS/MS analysis, four anthocyanins, three biflavonoids, gallic acid, and two
      types of hydrolyzable tannins (galloyl glucoses, galloyl shikimic acids) were
      tentatively identified. The structure of the so far unknown 7-O
      methylpelargonidin 3-O-beta-D-galactopyranoside was elucidated by 2D NMR. Within
      the group of gallotannins, galloyl shikimic acids with uncommon degrees of
      galloylation (tetra- to hexagalloyl shikimic acids) were detected. Among the
      biflavonoids, I3',II8-biapigenin (amentoflavone), I6,II8-biapigenin
      (agathisflavone), and II-2,3-dihydro-I3',II8-biapigenin were identified, which
      have already been described for Anacardiaceae. From the results of the present
      study together with previous findings on the phenolic profile of other
      Anacardiaceae plants, it is concluded that 7-methoxylated flavonoids are a
      chemotaxonomic trait frequently found in this family.

PMID- 24881809
TI  - Intracellular drug concentration and disposition--the missing link?
AB  - Improved understanding of the concentration of a potential drug molecule at the
      site of action in physiologically relevant cells or tissues has emerged as a key
      challenge in the early stages of drug discovery. Improved ability to carry out
      such studies with label-free methodology has the potential to improve
      understanding of drug uptake and trafficking and thus contribute to the reduction
      of rates of attrition in drug discovery. 

PMID- 24881810
TI  - The use of SmartPill for gastric monitoring.
AB  - Testing to define delayed gastric emptying is required to diagnose gastroparesis;
      rapid emptying is found in other patients. Commonly performed methods of gastric
      emptying testing include scintigraphy and breath testing. The SmartPill wireless
      motility capsule (WMC) system is US FDA-approved for evaluating suspected delayed
      emptying in gastroparesis and functional dyspepsia. The device measures transit
      in the stomach, small intestine, and colon by detecting characteristic pH
      transitions; and quantifies pressure waves in each gut region. WMC gastric
      emptying times correlate with scintigraphic measures. Incremental benefits of WMC
      testing in patients with suspected gastroparesis include delineation of pressure
      abnormalities and small intestinal and colonic transit delays. Acceptance of
      trial data confirming usefulness of WMC testing in suspected gastric motor
      disorders has been hampered by small sample sizes and design limitations. Ongoing
      multicenter studies will validate the utility of WMC methods in patients with
      suspected gastroparesis and other upper gastrointestinal motor disorders. 

PMID- 24881812
TI  - ITS2, 18S, 16S or any other RNA - simply aligning sequences and their individual
      secondary structures simultaneously by an automatic approach.
AB  - Secondary structures of RNA sequences are increasingly being used as additional
      information in reconstructing phylogenies and/or in distinguishing species by
      compensatory base change (CBC) analyses. However, in most cases just one
      secondary structure is used in manually correcting an automatically generated
      multiple sequence alignment and/or just one secondary structure is used in
      guiding a sequence alignment still completely generated by hand. With the advent
      of databases and tools offering individual RNA secondary structures, here we re
      introduce a twelve letter code already implemented in 4SALE - a tool for
      synchronous sequence and secondary structure alignment and editing - that enables
      one to align RNA sequences and their individual secondary structures
      synchronously and fully automatic, while dramatically increasing the phylogenetic
      information content. We further introduce a scaled down non-GUI version of 4SALE
      particularly designed for big data analysis, and available at:
      http://4sale.bioapps.biozentrum.uni-wuerzburg.de. 

PMID- 24881811
TI  - Neurofunctional dopaminergic impairment in elderly after lifetime exposure to
      manganese.
AB  - BACKGROUND: Manganese (Mn) is an essential element that can become neurotoxic
      through various exposure windows over the lifespan. While there is clear evidence
      of Mn neurotoxicity in pediatric and adult occupational populations, little is
      known about effects in the elderly who may exhibit enhanced susceptibilities due
      to compromised physiology compared to younger adults. In the province of Brescia,
      Italy, the Valcamonica area has been the site of three ferroalloy plants
      operating from 1902 to 2001. Metal emissions of Mn and to a lesser extent lead
      (Pb) have impacted the surrounding environment, where a high prevalence of
      Parkinsonism was previously observed. This study aimed to assess neurocognitive
      and motor functions in healthy elderly subjects residing for most of their
      lifetime in Valcamonica or in a reference area unimpacted by ferroalloy plant
      activity. METHODS: Subjects were enrolled for extensive neurobehavioral
      assessment of motor, cognitive and sensory functions. Exposure was assessed with
      24h personal air sampling for PM10 airborne particles, surface soil and tap water
      measurement at individual households, Mn levels in blood and urine and Pb in
      blood. Dose-response relationships between exposure indicators and biomarkers and
      health outcomes were analyzed with generalized (linear and logistic) additive
      models (GAM). RESULTS: A total of 255 subjects (55% women) were examined; most
      (52.9%) were within the 65-70 years age class. Average airborne Mn was 26.41
      ng/m(3) (median 18.42) in Valcamonica and 20.96 ng/m(3) (median 17.62) in the
      reference area. Average Mn in surface soil was 1026 ppm (median 923) in
      Valcamonica and 421 ppm (median 410) in the reference area. Manganese in drinking
      water was below the LDL of 1 MUg/L. The GAM analysis showed significant
      association between airborne Mn (p=0.0237) and the motor coordination tests of
      the Luria Nebraska Neuropsychological Battery. The calculation of the Benchmark
      Dose using this dose-response relationship yielded a lower level confidence
      interval of 22.7 ng/m(3) (median 26.4). For the odor identification score of the
      Sniffin Stick test, an association was observed with soil Mn (p=0.0006) and with
      a significant interaction with blood Pb (p=0.0856). Significant dose-responses
      resulted also for the Raven's Colored Progressive Matrices with the distance from
      exposure point source (p=0.0025) and Mn in soil (p=0.09), and for the Trail
      Making test, with urinary Mn (p=0.0074). Serum prolactin (PRL) levels were
      associated with air (p=0.061) and urinary (p=0.003) Mn, and with blood Pb
      (p=0.0303). In most of these associations age played a significant role as an
      effect modifier. CONCLUSION: Lifelong exposure to Mn was significantly associated
      with changes in odor discrimination, motor coordination, cognitive abilities and
      serum PRL levels. These effects are consistent with the hypothesis of a specific
      mechanism of toxicity of Mn on the dopaminergic system. Lead co-exposure, even at
      very low levels, can further enhance Mn toxicity.

PMID- 24881814
TI  - Polymorphisms in the promoter region of ESR2 gene and susceptibility to ovarian
      cancer.
AB  - Susceptibility to ovarian cancer might be affected by genetic variations in genes
      involved in estrogen biosynthesis, metabolism or signal transduction. In this
      study we tested the hypothesis that single nucleotide polymorphisms (SNPs) in the
      promoter of human ESR2 gene, coding for estrogen receptor beta, may be associated
      with increased risk for ovarian cancer. Three SNPs in the promoter region of
      human ESR2 gene were genotyped by means of allele-specific tetra-primer PCR. A
      total of 184 ovarian cancer cases and the same numbers of controls were included
      in the study. With regard to homozygous analysis, the AA genotype of SNP
      rs3020449 was found to be significantly more frequent in ovarian cancer cases
      staged as FIGO III+IV than in cases staged as I+II (OR 2.717, p=0.027). With
      regard to allele frequency, the G allele of this SNP was less frequent in FIGO
      I+II cases than in cases with higher FIGO stages (OR 1.739, p=0.018). With regard
      to genotype frequency, allele frequency, allele positivity or haplotype frequency
      of SNPs rs2987983, rs3020449 and rs3020450 we did not observe a significant
      difference between the cancer and the control group. Our data suggest that SNPs
      in the promoter region of ESR2 gene do not affect susceptibility to ovarian
      cancer, but SNP rs3020449 might affect progression of this disease. 

PMID- 24881813
TI  - Epigenetic landscape during osteoblastogenesis defines a differentiation
      dependent Runx2 promoter region.
AB  - Runx2 is a developmentally regulated gene in vertebrates and is essential for
      bone formation and skeletal homeostasis. The induction of runx2-P1 isoform
      transcripts is a hallmark of early osteoblastogenesis. Although previous in vitro
      studies have defined a minimal Runx2-P1 promoter sequence with well-characterized
      functional elements, several lines of evidence suggest that transcription of the
      Runx2-P1 isoform relies on elements that extend beyond the previously defined P1
      promoter boundaries. In this study, we examined Runx2-P1 transcriptional
      regulation in a cellular in vivo context during early osteoblastogenesis of MC3T3
      E1 cultures and BMSCs induced towards the bone lineage by multi-layered analysis
      of the Runx2-P1 gene promoter using the following methodologies: 1) sequence
      homology among several mammalian species, 2) DNaseI hypersensitivity coupled with
      massively parallel sequencing (DNase-seq), and 3) chromatin immunoprecipitation
      of activating histone modifications coupled with massively parallel sequencing
      (ChIP-seq). These epigenetic features have allowed the demarcation of boundaries
      that redefine the minimal Runx2-P1 promoter to include a 336-bp sequence that
      mediates responsiveness to osteoblast differentiation. We also find that an
      additional level of control is contributed by a regulatory region in the 5'-UTR
      of Runx2-P1. 

PMID- 24881815
TI  - Molecular cloning and characterization of the beta-catenin gene from fine-wool
      sheep.
AB  - beta-Catenin is an evolutionarily conserved molecule that functions as a crucial
      effector in both cell-to-cell adhesion and Wnt signaling. To gain a better
      understanding of its role in the development of hair follicles, we cloned the
      cDNA sequence of the beta-catenin gene from the skin of Aohan fine-wool sheep and
      performed a variety of bioinformatics analyses. We obtained the full-length
      sequence, which was 4573-bp long and contained a 2346-bp open reading frame
      encoding a protein of 781 amino acids. The protein had a predicted molecular
      weight of 85.4 kDa and a theoretical isoelectric point of 5.57. Domain
      architecture analysis of the beta-catenin protein revealed an armadillo repeat
      region, which is a common feature of beta-catenin in other species. The ovine
      beta-catenin gene shares 97.91%, 94.25%, 94.59%, 83.89%, and 89.39% sequence
      identity with its homologs in Bos taurus, Homo sapiens, Sus scrofa, Gallus
      gallus, and Mus musculus, respectively, while the amino acid sequence is more
      than 99% identical with each of these species. The expression of beta-catenin
      mRNA was detected in the heart, liver, spleen, lung, kidney, skin, muscle, and
      adipose tissue. Expression levels were maximal in the lung and minimal in the
      muscle, and the difference in expression in these tissues was significant
      (P<0.01). Western blot analysis revealed the presence of the beta-catenin protein
      in all tissues examined; expression was lowest in the skin and adipose tissues.

PMID- 24881816
TI  - Predicting natural product value, an exploration of anti-TB drug space.
AB  - Covering: January 1990 to December 2012. Mycobacterium tuberculosis (Mtb) still
      remains a deadly pathogen two decades after the announcement of tuberculosis (TB)
      as a global health emergency by the World Health Organization. In last few years
      new drug combinations have shown promising potential to significantly shorten TB
      treatment times. However there are very few new chemical entities being developed
      to treat this global threat. From January 1990 to December 2012, 949 anti
      mycobacterium natural products were reported in the literature. Here we present a
      perspective based on an analysis of the drug-like properties of the reported anti
      mycobacterium natural products in order to assess drug potential.

PMID- 24881817
TI  - CCAAT/enhancer binding protein beta (C/EBPbeta) isoform balance as a regulator of
      epithelial-mesenchymal transition in mouse mammary epithelial cells.
AB  - Activation of the epithelial-mesenchymal transition (EMT) program promotes cell
      invasion and metastasis, and is reversed through mesenchymal-epithelial
      transition (MET) after formation of distant metastases. Here, we show that an
      imbalance of gene products encoded by the transcriptional factor C/EBPbeta, LAP
      (liver-enriched activating protein) and LIP (liver-enriched inhibitory protein),
      can regulate both EMT- and MET-like phenotypic changes in mouse mammary
      epithelial cells. By using tetracycline repressive LIP expression constructs, we
      found that SCp2 cells, a clonal epithelial line of COMMA1-D cells, expressed EMT
      markers, lost the ability to undergo alveolar-like morphogenesis in 3D Matrigel,
      and acquired properties of benign adenoma cells. Conversely, we found that
      inducible expression of LAP in SCg6 cells, a clonal fibroblastic line of COMMA1-D
      cells, began to express epithelial keratins with suppression of proliferation.
      The overexpression of the C/EBPbeta gene products in these COMMA1-D derivatives
      was suppressed by long-term cultivation on tissue culture plastic, but gene
      expression was maintained in cells grown on Matrigel or exposed to proteasome
      inhibitors. Thus, imbalances of C/EBPbeta gene products in mouse mammary
      epithelial cells, which are affected by contact with basement membrane, are
      defined as a potential regulator of metastatic potential. 

PMID- 24881818
TI  - A naringenin-tamoxifen combination impairs cell proliferation and survival of MCF
      7 breast cancer cells.
AB  - Since over 60% of breast cancers are estrogen receptor positive (ER+), many
      therapies have targeted the ER. The ER is activated by both estrogen binding and
      phosphorylation. While anti-estrogen therapies, such as tamoxifen (Tam) have been
      successful they do not target the growth factor promoting phosphorylation of the
      ER. Other proliferation pathways such as the phosphatidylinositol-3 kinase,
      (PI3K) and the mitogen-activated protein kinase (MAPK) pathways are activated in
      breast cancer cells and are associated with poor prognosis. Thus targeting
      multiple cellular proliferation and survival pathways at the onset of treatment
      is critical for the development of more effective therapies. The grapefruit
      flavanone naringenin (Nar) is an inhibitor of both the PI3K and MAPK pathways.
      Previous studies examining either Nar or Tam used charcoal-stripped serum which
      removed estrogen as well as other factors. We wanted to use serum containing
      medium in order to retain all the potential inducers of cell proliferation so as
      not to exclude any targets of Nar. Here we show that a Nar-Tam combination is
      more effective than either Tam alone or Nar alone in MCF-7 breast cancer cells.
      We demonstrate that a Nar-Tam combination impaired cellular proliferation and
      viability to a greater extent than either component alone in MCF-7 cells.
      Furthermore, the use of a Nar-Tam combination requires lower concentrations of
      both compounds to achieve the same effects on proliferation and viability. Nar
      may function by inhibiting both PI3K and MAPK pathways as well as localizing
      ERalpha to the cytoplasm in MCF-7 cells. Our results demonstrate that a Nar-Tam
      combination induces apoptosis and impairs proliferation signaling to a greater
      extent than either compound alone. These studies provide critical information for
      understanding the molecular mechanisms involved in cell proliferation and
      apoptosis in breast cancer cells. 

PMID- 24881819
TI  - PTEN and PI-3 kinase inhibitors control LPS signaling and the lymphoproliferative
      response in the CD19+ B cell compartment.
AB  - Pattern recognition receptors (PRRs), e.g. toll receptors (TLRs) that bind
      ligands within the microbiome have been implicated in the pathogenesis of cancer.
      LPS is a ligand for two TLR family members, TLR4 and RP105 which mediate LPS
      signaling in B cell proliferation and migration. Although LPS/TLR/RP105 signaling
      is well-studied; our understanding of the underlying molecular mechanisms
      controlling these PRR signaling pathways remains incomplete. Previous studies
      have demonstrated a role for PTEN/PI-3K signaling in B cell selection and
      survival, however a role for PTEN/PI-3K in TLR4/RP105/LPS signaling in the B cell
      compartment has not been reported. Herein, we crossed a CD19cre and PTEN(fl/fl)
      mouse to generate a conditional PTEN knockout mouse in the CD19+ B cell
      compartment. These mice were further crossed with an IL-14alpha transgenic mouse
      to study the combined effect of PTEN deletion, PI-3K inhibition and expression of
      IL-14alpha (a cytokine originally identified as a B cell growth factor) in CD19+
      B cell lymphoproliferation and response to LPS stimulation. Targeted deletion of
      PTEN and directed expression of IL-14alpha in the CD19+ B cell compartment (IL
      14+PTEN-/-) lead to marked splenomegaly and altered spleen morphology at baseline
      due to expansion of marginal zone B cells, a phenotype that was exaggerated by
      treatment with the B cell mitogen and TLR4/RP105 ligand, LPS. Moreover, LPS
      stimulation of CD19+ cells isolated from these mice display increased
      proliferation, augmented AKT and NFkappaB activation as well as increased
      expression of c-myc and cyclinD1. Interestingly, treatment of LPS treated IL
      14+PTEN-/- mice with a pan PI-3K inhibitor, SF1126, reduced splenomegaly, cell
      proliferation, c-myc and cyclin D1 expression in the CD19+ B cell compartment and
      normalized the splenic histopathologic architecture. These findings provide the
      direct evidence that PTEN and PI-3K inhibitors control TLR4/RP105/LPS signaling
      in the CD19+ B cell compartment and that pan PI-3 kinase inhibitors reverse the
      lymphoproliferative phenotype in vivo.

PMID- 24881820
TI  - Outcomes after intrauterine insemination are independent of provider type.
AB  - OBJECTIVE: We sought to determine whether the success of intrauterine
      insemination (IUI) varies based on the type of health care provider performing
      the procedure. STUDY DESIGN: This was a retrospective cohort study set at an
      infertility clinic at an academic institution. The patients who comprised this
      study were 1575 women who underwent 3475 IUI cycles from late 2003 through early
      2012. Cycles were stratified into 3 groups according to the type of provider who
      performed the procedure: attending physician, fellow physician, or registered
      nurse (RN). The primary outcome was live birth. Additional outcomes of interest
      included positive pregnancy test and clinical pregnancy. Repeated measures log
      binomial regression was used to estimate the risk ratios (RR) and 95% confidence
      intervals (CI) for the outcomes and to evaluate the effect of potential
      confounders. All tests were 2-sided, and P values < .05 were considered
      statistically significant. RESULTS: Of the 3475 IUI cycles, 2030 (58.4%) were
      gonadotropin stimulated, 929 (26.7%) were clomiphene citrate stimulated, and 516
      (14.9%) were natural. The incidences of clinical pregnancy and live birth among
      all cycles were 11.8% and 8.8%, respectively. After adjusting for female age,
      male partner age, and cycle type, the incidence of live birth was similar for RNs
      compared with attending physicians (RR, 0.80; 95% CI, 0.58-1.1) and fellow
      physicians compared with attending physicians (RR, 0.84; 95% CI, 0.58-1.2).
      Similar results were seen for positive pregnancy test and clinical pregnancy.
      CONCLUSION: There was no significant difference in live birth following IUI
      cycles in which the procedure was performed by a fellow physician or RN compared
      with an attending physician.

PMID- 24881822
TI  - The relationship between preeclampsia and intrauterine growth restriction in twin
      pregnancies.
AB  - OBJECTIVE: Preeclampsia and intrauterine growth restriction (IUGR) are correlated
      in singleton pregnancies. The objective of this study was to estimate their
      relationship in twin pregnancies. STUDY DESIGN: Cohort of 578 patients with twin
      pregnancies delivered by 1 maternal fetal medicine practice from 2005-2013.
      Patients with chronic hypertension, monochorionic-monoamniotic placentation, twin
      twin transfusion, and major congenital anomalies were excluded. Standard
      definitions were used for gestational hypertension and preeclampsia. We defined
      IUGR as any twin birthweight less than the 5th percentile for gestational age, as
      well as any twin birthweight less than the 10th percentile for gestational age.
      RESULTS: The incidence of preeclampsia was 14.9%, the incidence of birthweight
      <10% was 50.0%, and the incidence of birthweight <5% was 27.5%. Comparing
      patients with and without preeclampsia, the rate of birthweight <5th percentile
      did not differ (27.9% vs 27.4%, P = .929), nor did the rate of birthweight <10th
      percentile (48.8% vs 50.2%, P = .815). We had 80% power with an alpha error of 5%
      to show a difference in the likelihood of IUGR <10th percentile from 50% to 66%
      and a difference in the likelihood of IUGR <5th percentile from 27% to 42% in
      patients without and with preeclampsia. CONCLUSION: In patients with twin
      pregnancy, there is no correlation between preeclampsia and IUGR. This suggests
      that in twin pregnancies, as opposed to singleton pregnancies, the
      pathophysiology may differ between these 2 common conditions.

PMID- 24881821
TI  - Developing a systematic approach to safer medication use during pregnancy:
      summary of a Centers for Disease Control and Prevention--convened meeting.
AB  - To address information gaps that limit informed clinical decisions on medication
      use in pregnancy, the Centers for Disease Control and Prevention (CDC) solicited
      expert input on a draft prototype outlining a systematic approach to evaluating
      the quality and strength of existing evidence for associated risks. The draft
      prototype outlined a process for the systematic review of available evidence and
      deliberations by a panel of experts to inform clinical decision making for
      managing health conditions in pregnancy. At an expert meeting convened by the CDC
      in January 2013, participants divided into working groups discussed decision
      points within the prototype. This report summarizes their discussions of best
      practices for formulating an expert review process, developing evidence summaries
      and treatment guidance, and disseminating information. There is clear recognition
      of current knowledge gaps and a strong collaboration of federal partners,
      academic experts, and professional organizations willing to work together toward
      safer medication use during pregnancy. 

PMID- 24881824
TI  - Clinical faculty: taking the lead in teaching quality improvement and patient
      safety.
AB  - Despite efforts by health professional organizations to promote efforts in
      quality improvement, patient safety, and cost reduction, the issue remains that
      US medical schools and teaching hospitals do not have an adequate supply of
      skilled faculties to lead these efforts. Recognizing this need, an expert,
      multidisciplinary panel was convened by the American Association of Medical
      Colleges in 2012 to develop a systematic strategy to build a critical mass of
      academic health center faculties to lead and implement education in those three
      areas. In the last year, the American Association of Medical Colleges has
      launched a national institution-based initiative to train faculty in all clinical
      specialties, which includes those in obstetrics-gynecology. This comprehensive
      program consists of interactive experiential learning workshops, web-based
      resources, a national community of learners, implementation of educational
      initiatives, and dissemination of outcomes. Those faculties will be invaluable in
      leading and disseminating educational programs that embed quality improvement and
      patient safety across the continuum of women's healthcare to all faculty members
      and residents. 

PMID- 24881823
TI  - Effect of umbilical cord milking on morbidity and survival in extremely low
      gestational age neonates.
AB  - OBJECTIVE: Delayed umbilical cord clamping benefits extremely low gestational age
      neonates (ELGANs) but has not gained wide acceptance. We hypothesized that
      milking the umbilical cord (MUC) would avoid resuscitation delay but improve
      hemodynamic stability and reduce rates for composite outcome of severe
      intraventricular hemorrhage, necrotizing enterocolitis, and/or death before
      discharge. STUDY DESIGN: We implemented a joint neonatal/maternal-fetal quality
      improvement process for MUC starting September 2011. The MUC protocol specified
      that infants who were born at <30 weeks of gestation undergo MUC 3 times over a
      duration of <30 seconds at delivery. Obstetric and neonatal data were collected
      until discharge. We compared the MUC group to retrospective ELGAN cohort
      delivered at our center between January 2010 and August 2011. Analysis was
      intention-to-treat. RESULTS: We identified 318 ELGANs: 158 eligible for MUC and
      160 retrospective control neonates. No adverse events were reported with cord
      milking. There was no difference in neonatal resuscitation, Apgar scores, or
      admission temperature. Hemodynamic stability was improved in the MUC group with
      higher mean blood pressures through 24 hours of age, despite less vasopressor use
      (18% vs 32%; P < .01). The initial hematocrit value was higher (50% vs 45%; P <
      .01), and red cell transfusions were fewer (57% vs 79%; P < .01) in MUC vs
      control infants. Presence of the composite outcome was significantly less in MUC
      vs the historic control infants (22% v 39%; odds ratio, 1.81; 95% confidence
      interval, 1.06-3.10). There were also reductions in intraventricular hemorrhage,
      necrotizing enterocolitis, and death before hospital discharge. CONCLUSION: MUC
      improves early hemodynamic stability and is associated with lower rates of
      serious morbidity and death among ELGANs.

PMID- 24881825
TI  - Amnioreduction in the management of polyhydramnios complicating singleton
      pregnancies.
AB  - OBJECTIVE: The purpose of this study was to evaluate the contribution of
      amnioreduction to the management of singleton pregnancies that are complicated by
      symptomatic polyhydramnios. STUDY DESIGN: Retrospective review of all singleton
      pregnancies that received at least 1 amnioreduction for polyhydramnios from 2000
      2012 at a single obstetric unit that provides a statewide service. The
      indications, procedural techniques, and pregnancy outcomes were evaluated.
      RESULTS: One hundred thirty-eight women with polyhydramnios (maximal vertical
      pocket [MVP], >=8 cm) had 271 amnioreduction procedures during the study period.
      The median gestation at the first drain was 31.4 weeks (interquartile range, 28.4
      34 weeks) and a median of 1 procedure (interquartile range, 1-2 procedures) was
      performed per pregnancy. Sixty-three women (45.6%) required >1 amnioreduction.
      The median volume removed per pregnancy was 2100 mL (interquartile range, 1500
      4260 mL). The median duration from the first amnioreduction until delivery was 26
      days (interquartile range, 15-52.5 days). There was no significant association
      between gestation at delivery and the volume per procedure or total volume that
      was removed. Earlier gestation at first drain was associated positively with
      earlier gestations at delivery. In 4.1% of amnioreduction procedures (11/271
      procedures), there was an unplanned preterm birth within 48 hours. The median
      gestation at delivery was 36.4 weeks (interquartile range, 34-38 weeks). The
      final diagnoses were gastrointestinal malformations (21%), idiopathic
      polyhydramnios (20.3%), chromosomal anomaly (15.2%), syndromic condition (13.7%),
      and neurologic condition (8%). CONCLUSION: Amnioreduction has a useful role in
      the management of polyhydramnios in singleton pregnancies. Complications are
      uncommon, and delivery typically occurs near term.

PMID- 24881827
TI  - Does treatment for cervical and vulvar dysplasia impact women's sexual health?
AB  - Human papillomavirus-associated disease represents an immense public health
      burden worldwide. Persistent human papillomavirus infection can lead to the
      development of cervical dysplasia and vulvar dysplasia, both of which have been
      increasing in incidence in women in recent years. Numerous studies have focused
      on methods for screening and diagnosis of cervical dysplasia, but few have looked
      at the effects of treatment on women's psychological and sexual health. Even
      fewer studies have addressed these issues in women with vulvar dysplasia. The aim
      of this article was to provide a comprehensive review of the existing evidence
      concerning the impact of therapy for cervical and vulvar precancers on women's
      sexual function and sexual relationships. We performed a search of the medical
      literature for the time period up to and including August 2013 on PubMed. The
      findings from a limited number of studies to date indicate that psychosexual
      vulnerability increases after diagnosis and treatment of both cervical and vulvar
      dysplasia. More in-depth research is needed to better understand the effects of
      different treatment modalities on women's sexual health and relationships during
      and following treatment. 

PMID- 24881826
TI  - Angiogenic and inflammatory biomarkers in midpregnancy and small-for-gestational
      age outcomes in Tanzania.
AB  - OBJECTIVE: We sought to investigate the relationship between a panel of
      angiogenic and inflammatory biomarkers measured in midpregnancy and small-for
      gestational-age (SGA) outcomes in sub-Saharan Africa. STUDY DESIGN:
      Concentrations of 18 angiogenic and inflammatory biomarkers were determined in
      432 pregnant women in Dar es Salaam, Tanzania, who participated in a trial
      examining the effect of multivitamins on pregnancy outcomes. Infants falling
      below the 10th percentile of birthweight for gestational age relative to the
      applied growth standards were considered SGA. Multivariate binomial regression
      models with the log link function were used to determine the relative risk of SGA
      associated with increasing quartiles of each biomarker. Restricted cubic splines
      were used to test for nonlinearity of these associations. RESULTS: A total of 60
      participants (13.9%) gave birth to SGA infants. Compared to those in the first
      quartile, the risk of SGA was reduced among those in the fourth quartiles of
      vascular endothelial growth factor-A (adjusted risk ratio [RR], 0.38; 95%
      confidence interval [CI], 0.19-0.74), placental growth factor (adjusted RR, 0.28;
      95% CI, 0.12-0.61), soluble fms-like tyrosine kinase-1 (adjusted RR, 0.48; 95%
      CI, 0.23-1.01), monocyte chemoattractant protein-1 (adjusted RR, 0.48; 95% CI,
      0.25-0.92), and leptin (adjusted RR, 0.46; 95% CI, 0.22-0.96). CONCLUSION: Our
      findings provide evidence of altered angiogenic and inflammatory mediators, at
      midpregnancy, in women who went on to deliver SGA infants.

PMID- 24881828
TI  - Screening practices and attitudes of obstetricians-gynecologists toward new and
      emerging tobacco products.
AB  - OBJECTIVE: We examined screening practices and attitudes of obstetricians
      gynecologists toward the use of noncombustible tobacco products (chewing tobacco,
      snuff/snus, electronic cigarettes, and dissolvables) during pregnancy. STUDY
      DESIGN: The authors mailed a survey in 2012 to 1024 members of the American
      College of Obstetricians and Gynecologists, including Collaborative Ambulatory
      Research Network (CARN) and non-CARN members. Stratified random selection was
      used to generate CARN and non-CARN samples. RESULTS: Response rates were 52% and
      31% for CARN and non-CARN members, respectively. Of 252 total eligible
      respondents (those currently providing obstetrics care) 53% reported screening
      pregnant women at intake for noncombustible tobacco product use all or some of
      the time, and 40% reported none of the time. Respondents who reported that
      noncombustible products have adverse health effects during pregnancy, but are
      safer than cigarettes, ranged from 20.2% (dissolvables) to 29% (electronic
      cigarettes) and that the health effects are the same as those of cigarettes from
      13.5% (electronic cigarettes) to 53.6% (chewing tobacco). Approximately 14%
      reported that electronic cigarettes have no adverse health effects; <1% reported
      no health effects for the remaining products. Two-thirds of the respondents
      wanted to know more about the potential health effects of noncombustible tobacco
      products; only 5% believed themselves to be fully informed. CONCLUSION: A large
      proportion of obstetrician-gynecologists reported never or inconsistently
      screening their pregnant patients for the use of noncombustible tobacco products.
      Responses regarding the harms of these products relative to cigarettes were mixed
      and most respondents wanted more information. Development and dissemination of
      guidance for providers is needed to improve decision-making regarding
      noncombustible tobacco products.

PMID- 24881830
TI  - Embryo transfer by reproductive endocrinology fellows vs attending physicians:
      are live birth rates comparable?
AB  - OBJECTIVE: To compare live birth rates following ultrasound-guided embryo
      transfer (ET) by reproductive endocrinology and infertility fellows versus
      attending physicians. STUDY DESIGN: Women who underwent their first day-3, fresh,
      nondonor ET between Oct. 1, 2005, and April 1, 2011, at our academic center were
      included in this retrospective cohort study. Embryos were designated high quality
      if they had 8 cells, less than 10% fragmentation, and no asymmetry. ET was
      performed with the afterload technique under ultrasound guidance. Categorical
      variables were evaluated with the chi(2) test and continuous variables with the
      Student t test. Logistic regression was performed to assess the relationship
      between ET physician and live birth rate while adjusting for potential
      confounders. RESULTS: Seven hundred sixty women underwent ET by an attending
      physician, and 104 by a fellow. Baseline characteristics were similar between the
      groups. The live birth rate was 31% following ET by an attending physician,
      compared with 34% following ET by a fellow (P = .65). Logistic regression
      adjusting for potential confounders demonstrated no significant association
      between ET physician and live birth rate. CONCLUSION: This retrospective study
      demonstrated no significant difference in live birth rates following ultrasound
      guided ET by fellows vs attending physicians at our institution. These data
      suggest that academic practices using the afterload method and ultrasound
      guidance can train fellows to perform ET without compromising success rates.

PMID- 24881829
TI  - Development and testing of an iOS waiting room "app" for contraceptive counseling
      in a Title X family planning clinic.
AB  - OBJECTIVE: Long-acting reversible contraceptive (LARC) methods, such as the
      intrauterine device and implant, are highly effective but used by less than 10%
      of US women. The objective of our study was to improve LARC interest by enhancing
      clinic counseling. STUDY DESIGN: A quality improvement methodology was used to
      evaluate intrauterine device service delivery in 3 Chicago Title X clinics. To
      address identified barriers, we developed a theory-based iOS application (app)
      for patients to use in the clinic waiting room using human-centered design. The
      final prototype was tested in a randomized controlled trial in a Title X clinic
      with sexually active females (79% African American) under age 30 years. Our
      sample of 60 was chosen to detect an increase from 10% (baseline) to 45% (app
      intervention) in the proportion of patients expressing interest in discussing a
      LARC method during their clinic visit with 80% power and two-sided alpha = 0.05.
      After completing demographic and baseline knowledge questionnaires, participants
      were randomized 1:1 to intervention (app) or standard care arms. App users also
      completed a posttest. Our primary outcome was expressed interest in discussing a
      LARC method during the clinic visit. Secondary outcomes were contraceptive
      knowledge and LARC selection. RESULTS: App testers (n = 17) preferred
      interactive, visually appealing design and video testimonials. In the pilot
      randomized controlled trial (n = 52), app users had a significantly higher
      knowledge of contraceptive effectiveness (P = .0001) and increased interest in
      the implant (7.1-32.1%, P = .02) after the intervention. Users were highly
      satisfied with the app. Staff reported no problems using the app in the clinic.
      CONCLUSION: Use of a theory-based counseling app offers a novel method to
      optimize wait time while minimizing clinic flow disruption. Preliminary data
      demonstrate that app use was associated with improvements in patients'
      contraceptive knowledge and interest in the implant.

PMID- 24881831
TI  - Clinical significance of amniotic fluid sludge in twin pregnancies with a short
      cervical length.
AB  - OBJECTIVE: The objective of the study was to determine the clinical significance
      of amniotic fluid (AF) sludge in twin pregnancies with a short cervix. STUDY
      DESIGN: We evaluated twin pregnancies with a short cervical length that had an
      ultrasound between 16 and 26 weeks (n = 78). Pregnancy outcomes in those with
      sludge (n = 27) and those without (n = 51) were compared. Outcome variables
      included gestational age at delivery, premature rupture of the membranes,
      chorioamnionitis, funisitis, composite neonatal morbidity, and perinatal death.
      For statistical analysis, the first-born (A) and second-born (B) twins were
      studied separately. RESULTS: The prevalence of AF sludge was 34.6% (27 of 78).
      Pregnancies with sludge delivered earlier (27.2 +/- 5.6 weeks vs 31.0 +/- 4.05
      weeks, P < .01) and had a higher rate of extreme prematurity (<26 weeks: 52.2%
      [12 of 23] vs 15.6% [5 of 32]; P < .01). Both twins had higher rates of
      histological chorioamnionitis (twin A, 50.0% [13 of 26] vs 12.8% [6 of 47]; P <
      .01; twin B, 42.3% [11 of 26] vs 13.3% [6 of 45]; P < .01) and neonatal death
      (twin A, 33.3% [9 of 27] vs 3.9% [2 of 51]; P < .01; twin B, 33.3% [9 of 27] vs
      6.0% [3 of 50]; P = .01). Higher rates of funisitis (23.1% [6 of 26] vs 4.3% [2
      of 47]; P = .02) and composite neonatal morbidity were observed for twin A only
      (66.7% [14 of 21] vs 37.5% [18 of 48]; P = .04). CONCLUSION: The presence of AF
      sludge in twin pregnancies with a short cervix is a risk factor for extreme
      prematurity, histological chorioamnionitis, and perinatal death. Twin A had
      higher rates of funisitis and neonatal morbidity in the presence of AF sludge.

PMID- 24881832
TI  - Misperception of estrogen activity in patients treated with an estrogen receptor
      antagonist.
AB  - Measurement of estradiol is an important marker of ovarian function. At low
      levels, accurate measurement has been difficult because of unique characteristics
      of immunoassay kits. We present this case to emphasize the importance of accurate
      estimation of estrogen activity and estradiol levels to avoid unnecessary
      surgical intervention. 

PMID- 24881833
TI  - Reverse shoulder arthroplasty in 41 patients with cuff tear arthropathy with a
      mean follow-up period of 5 years.
AB  - BACKGROUND: Reverse shoulder arthroplasty (RSA) is an accepted treatment for
      patients with pseudoparalysis due to cuff tear arthropathy. There have been
      limited studies with midterm clinical and radiologic results. We present our
      results for a single surgeon from a district general hospital. METHODS: Forty-one
      consecutive Delta III RSAs were performed by an anterosuperior approach in 37
      patients (29 women and 8 men) with pseudoparalysis due to cuff tear arthropathy.
      The patients' mean age was 79 years (range, 68-91 years). The mean follow-up
      period was 5 years. All patients were available for final review, and none were
      lost to follow-up. RESULTS: The mean age-adjusted Constant and Oxford scores
      improved from 34.2 points to 71.0 points and 15 points to 33 points,
      respectively. Mean abduction and forward flexion improved from 64 degrees  to 100
      degrees  and 55 degrees  to 110 degrees , respectively. Scapular notching was
      seen in 68% of patients, but there was no deterioration in function or
      satisfaction scores. Stress shielding of the proximal humerus was seen in 10% of
      patients. One patient underwent revision to a hemiarthroplasty because of glenoid
      component failure after a fall. There were no early postoperative dislocations in
      our series. CONCLUSION: RSA for pseudoparalysis due to cuff tear arthropathy
      provides good functional results at 5 years; however, there is a high rate of
      scapular notching, which does not seem to affect overall functional outcomes.

PMID- 24881834
TI  - Multipoint-emitting optical fibers for spatially addressable in vivo
      optogenetics.
AB  - Optical stimulation and silencing of neural activity is a powerful technique for
      elucidating the structure and function of neural circuitry. In most in vivo
      optogenetic experiments, light is delivered into the brain through a single
      optical fiber. However, this approach limits illumination to a fixed volume of
      the brain. Here a focused ion beam is used to pattern multiple light windows on a
      tapered optical fiber. We show that such fibers allow selective and dynamic
      illumination of different brain regions along the taper. Site selection is
      achieved by a simple coupling strategy at the fiber input, and the use of a
      single tapered waveguide minimizes the implant invasiveness. We demonstrate the
      effectiveness of this approach for multipoint optical stimulation in the
      mammalian brain in vivo by coupling the fiber to a microelectrode array and
      performing simultaneous extracellular recording and stimulation at multiple sites
      in the mouse striatum and cerebral cortex.

PMID- 24881836
TI  - Acute retinal arterial ischemia: an emergency often ignored.

PMID- 24881835
TI  - Reward value comparison via mutual inhibition in ventromedial prefrontal cortex.
AB  - Recent theories suggest that reward-based choice reflects competition between
      value signals in the ventromedial prefrontal cortex (vmPFC). We tested this idea
      by recording vmPFC neurons while macaques performed a gambling task with
      asynchronous offer presentation. We found that neuronal activity shows four
      patterns consistent with selection via mutual inhibition: (1) correlated tuning
      for probability and reward size, suggesting that vmPFC carries an integrated
      value signal; (2) anti-correlated tuning curves for the two options, suggesting
      mutual inhibition; (3) neurons rapidly come to signal the value of the chosen
      offer, suggesting the circuit serves to produce a choice; and (4) after
      regressing out the effects of option values, firing rates still could predict
      choice-a choice probability signal. In addition, neurons signaled gamble
      outcomes, suggesting that vmPFC contributes to both monitoring and choice
      processes. These data suggest a possible mechanism for reward-based choice and
      endorse the centrality of vmPFC in that process. 

PMID- 24881837
TI  - Metamorphopsia and optical coherence tomography findings after rhegmatogenous
      retinal detachment surgery.

PMID- 24881838
TI  - Impact of crystalline lens opacification on effective phacoemulsification time in
      femtosecond laser-assisted cataract surgery.

PMID- 24881839
TI  - Reply: To PMID 24099274.

PMID- 24881840
TI  - Reply: To PMID 24210764.

PMID- 24881841
TI  - Clinical results of ab interno trabeculotomy using the Trabectome for open-angle
      glaucoma: the mayo clinic series in Rochester, Minnesota.

PMID- 24881842
TI  - Reply: To PMID 23954209.

PMID- 24881843
TI  - Reply: To PMID 24345319.

PMID- 24881844
TI  - Relationship between preferred sleeping position and asymmetric visual-field loss
      in open-angle glaucoma patients.

PMID- 24881845
TI  - Teaching ophthalmoscopy to medical students (the TOTeMS study).

PMID- 24881846
TI  - Reply: To PMID 24041982.

PMID- 24881847
TI  - Teaching ophthalmoscopy to medical students (the TOTeMS Study).

PMID- 24881848
TI  - Outcomes of repeat descemetopexy in post-cataract surgery descemet membrane
      detachment.

PMID- 24881849
TI  - Reply: To PMID 24041982.

PMID- 24881850
TI  - Reply: To PMID 24246573.

PMID- 24881851
TI  - Reply: To PMID 24011524.

PMID- 24881852
TI  - Predictability of intraocular lens power calculation formulae in infantile eyes
      with unilateral congenital cataract: results from the infant aphakia treatment
      study.

PMID- 24881853
TI  - A prediction model for liver abscess developing after transarterial
      chemoembolization in patients with hepatocellular carcinoma.
AB  - BACKGROUND: Liver abscess is a rare but potentially fatal complication of
      transarterial chemoembolization. Other than for biliary abnormalities, risk
      factors for liver abscess formation after transarterial chemoembolization have
      rarely been discussed. AIMS: To identify other risk factors of liver abscess
      after transarterial chemoembolization in patients with hepatocellular carcinoma.
      METHODS: Data for 5299 patients with hepatocellular carcinoma who underwent
      transarterial chemoembolization from July 1999 to December 2009 were
      retrospectively reviewed. 72 patients who experienced liver abscess after
      transarterial chemoembolization were enrolled as a case group, which was compared
      with a randomly selected control group (n=1009) of patients who did not develop
      liver abscess after transarterial chemoembolization. RESULTS: Pneumobilia, type 2
      biliary abnormality, type 1 biliary abnormality, diabetes mellitus, tumour number
      (>=3), tumour size (>=3cm), and tumour necrosis on the pre-transarterial
      chemoembolization computed tomography, and gelfoam embolization and vessel injury
      during transarterial chemoembolization were all significant predisposing factors
      for liver abscess after transarterial chemoembolization. A prediction model for
      postembolization liver abscess was developed from these risk factors. CONCLUSION:
      The group of patients with risk scores greater than 71 showed a significantly
      increased risk of liver abscess after transarterial chemoembolization. These high
      risk patients should be monitored carefully after transarterial
      chemoembolization.

PMID- 24881854
TI  - Hepatectomised patient sera promote hepatocyte differentiation of human-induced
      pluripotent stem cells.
AB  - BACKGROUND: Human induced pluripotent stem cells, which can be differentiated
      into hepatocyte-like cells, could provide a source for liver regeneration and bio
      artificial liver devices. However, the functionality of hepatocyte-like cells is
      significantly lower than that of primary hepatocytes. AIMS: To investigate
      whether serum from patients undergoing hepatectomy might promote differentiation
      from human induced pluripotent stem cells to hepatocyte-like cells. METHODS:
      Serum from patients undergoing hepatectomy (acquired pre-hepatectomy and 3 hours,
      1 day and 3 days post-hepatectomy) was used to replace foetal bovine serum when
      differentiating human induced pluripotent stem cells into hepatocyte-like cells.
      Properties of hepatocyte-like cells were assessed and compared with cells
      cultured in foetal bovine serum. RESULTS: The differentiation efficiency and
      functionality of hepatocyte-like cells cultured in human serum 3 hours and 1 day
      post-hepatectomy were superior to those cultured in foetal bovine serum and human
      serum pre-hepatectomy. Human serum 3 days post-hepatectomy had an equal effect to
      that of human serum pre-hepatectomy. Some cytochrome P450 isozyme transcript
      levels of hepatocyte-like cells cultured in human serum were higher than those
      cultured in foetal bovine serum. CONCLUSION: Human serum, particularly that
      acquired relatively soon after hepatectomy, can enhance the differentiation
      efficiency and functionality of hepatocyte-like cells derived from human induced
      pluripotent stem cells.

PMID- 24881855
TI  - Bleeding localized amyloidosis of the colon.

PMID- 24881858
TI  - Development of the detection threshold concept from a close look at sorption
      occurrence inside a glass vial based on the in-vial vaporization of semivolatile
      fatty acids.
AB  - Headspace (HS) analysis has been recommended as one of the most optimal methods
      for extracting and analyzing volatile organic compounds from samples in diverse
      media such as soil and water. Short-chain volatile fatty acids (VFA, C3-C7) with
      strong adsorptivity were selected as the target compounds to assess the basic
      characteristics of the HS analysis through simulation of HS conditions by in-vial
      vaporization of liquid-phase standards (VL) in 25 mL glass vials. The reliability
      of the VL approach was assessed by apportioning the in-vial VFA mass into three
      classes: (1) vaporized fraction, (2) dynamic adsorption on the vial walls
      (intermediate stage between vaporization and irreversible absorption), and (3)
      irreversible absorptive loss (on the vial wall). The dynamic adsorption
      partitioning inside the vial increased with n-VFA carbon number, e.g., 43% (C2:
      acetic acid, extrapolated value), 65% (C3: propanoic acid), and 98% (C7:
      heptanoic acid). The maximum irreversible losses for the studied n-VFAs exhibited
      a quadratic relationship with carbon number. If the detection threshold limit
      (DTL: the onset of mass detection after attaining the maximum irreversible loss)
      is estimated, the DTL values for target VFAs were in the range of 101 ng for i
      valeric acid to 616 ng for propionic acid, which are larger than the method
      detection limit by about 3 orders of magnitude. Consequently, quantitation of
      VFAs using the VL approach should be critically assessed by simultaneously
      considering the DTL criterion and the initial VFA masses loaded into the vial. 

PMID- 24881859
TI  - Transcatheter versus surgical aortic valve replacement in patients with prior
      coronary artery bypass graft operation: a PARTNER trial subgroup analysis.
AB  - BACKGROUND: The Placement of Aortic Transcatheter Valves (PARTNER) trial reported
      a reduced rate of mortality in patients with previous coronary bypass grafting
      (CABG) operation who received surgical aortic valve replacement (SAVR) in
      comparison with transcatheter aortic valve replacement (TAVR). We sought to
      further evaluate these groups. METHODS: We reviewed the database of the 699
      patients enrolled in the PARTNER trial. The cohort for this study consisted of
      288 patients (41.2%) who had a history of CABG operation before enrollment in the
      PARTNER trial. All patients were followed up for 2 years. RESULTS: The mean age
      was 81.5+/-6.6 years, and 231 patients (80.2%) were men. The preoperative
      characteristics were similar in 140 patients (48.6%) who received SAVR and 148
      (51.4%) who received TAVR. There were no differences between the two groups with
      respect to the operative outcomes of death, stroke, and myocardial infarction,
      but the TAVR patients experienced more paravalvular regurgitation (p<0.0001). At
      2 years, there was a trend toward greater all-cause mortality in the TAVR
      patients (hazard ratio [HR] 1.53; 95% confidence interval [CI]: 0.99, 2.35;
      p=0.052). Furthermore, the TAVR patients had more repeated hospitalization (HR
      1.75; 95% CI: 0.99, 3.07; p=0.05), death of any cause or repeated hospitalization
      (HR 1.52; 95% CI: 1.06, 2.19; p=0.02), and death of any cause or stroke (HR 1.51;
      95% CI: 1.00, 2.27; p=0.05). CONCLUSIONS: The 2-year follow-up of patients with a
      history of previous CABG operation in the PARTNER trial demonstrated improved
      outcomes with SAVR in comparison with TAVR. Further longitudinal assessment is
      necessary to corroborate these findings and to understand the possible causes.

PMID- 24881856
TI  - Pluronic modified leptin with increased systemic circulation, brain uptake and
      efficacy for treatment of obesity.
AB  - Modification of hydrophilic proteins with amphiphilic block copolymers capable of
      crossing cell membranes is a new strategy to improve protein delivery to the
      brain. Leptin, a candidate for the treatment of epidemic obesity, has failed in
      part because of impairment in its transport across the blood-brain barrier (BBB)
      that develops with obesity. We posit that modification of leptin with
      poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide), Pluronic P85
      (P85) might permit this protein to penetrate the BBB independently of its
      transporter, thereby overcoming peripheral leptin resistance. Here we report that
      peripherally administered leptin-P85 conjugates exhibit biological activity by
      reducing food intake in mouse models of obesity (ob/ob, and diet-induced obese
      mouse). We further generated two new leptin-P85 conjugates: one, Lep(ss)-P85(L),
      containing one P85 chain and another, Lep(ss)-P85(H), containing multiple P85
      chains. We report data on their purification, analytical characterization,
      peripheral and brain pharmacokinetics (PK). Lep(ss)-P85(L) crosses the BBB using
      the leptin transporter, and exhibits improved peripheral PK along with increased
      accumulation in the brain compared to unmodified leptin. Lep(ss)-P85(H) also has
      improved peripheral PK but in a striking difference to the first conjugate
      penetrates the BBB independently of the leptin transporter via a non-saturable
      mechanism. The results demonstrate that leptin analogs can be developed through
      chemical modification of the native leptin with P85 to overcome leptin resistance
      at the level of the BBB, thus improving the potential for the treatment of
      obesity. 

PMID- 24881860
TI  - Epidermal growth factor receptor is a prognosis predictor in patients with
      esophageal squamous cell carcinoma.
AB  - BACKGROUND: Our previous study indicated the survival rate for esophageal
      squamous cell cancer (ESCC) patients in stage III and positive lymph node groups
      with postoperative radiation therapy was significantly increased compared with
      surgery alone. But a predictive biomarker was needed to identify the patients who
      would benefit from postoperative radiotherapy. This study aims to evaluate
      epidermal growth factor receptor (EGFR) as an indicator to predict the prognosis
      of ESCC and to identify the patients who would benefit from postoperative
      radiotherapy. METHODS: Tissue samples were collected from our previous randomized
      study: 243 in the surgery alone group and 198 in the surgery plus radiotherapy
      group. Expression of EGFR was analyzed by immunohistochemical staining. RESULTS:
      The expression of EGFR is correlated with depth of tumor invasion (p=0.005),
      lymph node metastasis (p<0.001), and pathologic stage (p<0.001). The survival
      rate of patients with high EGFR expression is significantly lower than that of
      patients with low EGFR expression (p=0.000). Notably, in stage IIA cases, the 5
      year survival rate is 57.6% in the low EGFR expression group and 36.6% in the
      high expression group (p=0.020). EGFR is one of the independent variants that
      influence the prognosis. Moreover, for high EGFR expression patients the survival
      rate of the surgery plus radiotherapy group is higher than that of the surgery
      alone group (p=0.034). CONCLUSIONS: Expression of EGFR can be a prognostic
      predictor for ESCC. Patients with high expression of EGFR may benefit from
      postoperative radiation therapy.

PMID- 24881861
TI  - Acute kidney injury after on-pump or off-pump coronary artery bypass grafting in
      elderly patients.
AB  - BACKGROUND: An exploratory analysis of the German Off Pump Coronary Artery Bypass
      Grafting in Elderly Patients (GOPCABE) trial was performed to investigate the
      effect of off-pump coronary artery bypass grafting (CABG) on kidney function
      after the operation. METHODS: Data on kidney function were available from 1,612
      patients, representing 67% of the study population. Preoperative kidney function
      was graded according to the glomerular filtration rate. Acute kidney injury (AKI)
      within the first week after the operation was defined and classified according to
      the Acute Kidney Injury Network (AKIN) criteria. The incidence and severity of
      AKI was compared between patients operated on on-pump or off-pump. RESULTS:
      Impaired kidney function was seen in 642 patients (40%), and 19 patients had
      preexisting end-stage kidney disease. AKI of any severity occurred in half of all
      patients undergoing CABG, with AKIN stage 1 accounting for most of the cases. The
      incidence and severity of AKI in patients undergoing on-pump vs off-pump CABG was
      AKIN stage 1: 298 (37%) vs 329 (42%); AKIN stage 2: 38 (5%) vs 43 (5%); and AKIN
      stage 3: 44 (6%) vs 44 (6%), which did not differ significantly (p=0.174). New
      renal replacement therapy was necessary in 3.2% (on-pump) and in 2.7% (off-pump)
      of all patients. Stratification according to preoperative kidney function yielded
      comparable frequencies of AKI for on-pump and off-pump CABG. CONCLUSIONS: AKI was
      common in elderly patients undergoing CABG, but deterioration of kidney function
      requiring renal replacement therapy was a rare event. Off-pump CABG was not
      associated with decreased rates or reduced severity of AKI in elderly patients.

PMID- 24881862
TI  - Significance of positive mediastinal cultures in pediatric cardiovascular
      surgical procedure patients undergoing delayed sternal closure.
AB  - BACKGROUND: Many pediatric cardiac surgery centers obtain mediastinal cultures at
      the time of delayed sternal closure (DSC). There are no recommendations regarding
      how to treat patients with positive cultures. We explored the clinical
      significance of positive mediastinal cultures with regard to surgical site
      infections (SSI). METHODS: A retrospective study was performed on all patients
      who underwent DSC at our institution between December 2006 and December 2011.
      National Healthcare Safety Network criteria were used to prospectively identify
      SSIs. Univariate and multivariate logistic regression analyses were performed to
      evaluate potential risk factors for SSI and predictors for positive mediastinal
      cultures obtained at DSC. RESULTS: A total of 178 patients underwent DSC during
      the study period; 155 patients met the eligibility criteria for the study and
      were included in the analysis. Of the 155 included patients, 11 patients (7.1%)
      experienced SSI. Patients with a positive mediastinal culture obtained at DSC
      were more likely to experience SSI than were patients with a negative culture
      (p=0.003). In univariate analysis, a positive mediastinal culture was the only
      factor associated with SSI (odds ratio [OR], 7.4; 95% confidence interval [CI],
      2.1 to 26.7). In multivariate analysis, age at operation>=2 weeks (adjusted OR
      [aOR], 4.9; 95% CI, 1.84 to 12.8), receipt of stress-dosed hydrocortisone while
      the chest was open (aOR, 2.9; 95% CI, 1.1 to 7.6), and gestational age<=37 weeks
      (aOR, 2.7; 95% CI, 1.01 to 7.27) were independent predictors for a positive
      mediastinal culture. CONCLUSIONS: Patients with positive mediastinal cultures
      obtained at DSC had a significantly higher rate of subsequent SSI, and a positive
      mediastinal culture was the only statistically significant predictor of SSI.

PMID- 24881864
TI  - Opening a band gap without breaking lattice symmetry: a new route toward robust
      graphene-based nanoelectronics.
AB  - Developing graphene-based nanoelectronics hinges on opening a band gap in the
      electronic structure of graphene, which is commonly achieved by breaking the
      inversion symmetry of the graphene lattice via an electric field (gate bias) or
      asymmetric doping of graphene layers. Here we introduce a new design strategy
      that places a bilayer graphene sheet sandwiched between two cladding layers of
      materials that possess strong spin-orbit coupling (e.g., Bi2Te3). Our ab initio
      and tight-binding calculations show that a proximity enhanced spin-orbit coupling
      effect opens a large (44 meV) band gap in bilayer graphene without breaking its
      lattice symmetry, and the band gap can be effectively tuned by an interlayer
      stacking pattern and significantly enhanced by interlayer compression. The
      feasibility of this quantum-well structure is demonstrated by recent experimental
      realization of high-quality heterojunctions between graphene and Bi2Te3, and this
      design also conforms to existing fabrication techniques in the semiconductor
      industry. The proposed quantum-well structure is expected to be especially robust
      since it does not require an external power supply to open and maintain a band
      gap, and the cladding layers provide protection against environmental degradation
      of the graphene layer in its device applications. 

PMID- 24881863
TI  - Biomechanical properties of the thoracic aneurysmal wall: differences between
      bicuspid aortic valve and tricuspid aortic valve patients.
AB  - BACKGROUND: The prevalence for thoracic aortic aneurysms (TAAs) is significantly
      increased in patients with a bicuspid aortic valve (BAV) compared with patients
      who have a normal tricuspid aortic valve (TAV). TAA rupture is a life-threatening
      event, and biomechanics-based simulations of the aorta may help to disentangle
      the molecular mechanism behind its development and progression. The present study
      used polarized microscopy and macroscopic in vitro tensile testing to explore
      collagen organization and mechanical properties of TAA wall specimens from BAV
      and TAV patients. METHODS: Circumferential sections of aneurysmal aortic tissue
      from BAV and TAV patients were obtained during elective operations. The
      distribution of collagen orientation was captured by a Bingham distribution, and
      finite element models were used to estimate constitutive model parameters from
      experimental load-displacement curves. RESULTS: Collagen orientation was almost
      identical in BAV and TAV patients, with a highest probability of alignment along
      the circumferential direction. The strength was almost two times higher in BAV
      samples (0.834 MPa) than in TAV samples (0.443 MPa; p<0.001). The collagen
      related stiffness (Cf) was significantly increased in BAV compared with TAV
      patients (Cf=7.45 MPa vs 3.40 MPa; p=0.003), whereas the elastin-related
      stiffness was similar in both groups. A trend toward a decreased wall thickness
      was seen in BAV patients (p=0.058). CONCLUSIONS: The aneurysmal aortas of BAV
      patients show a higher macroscopic strength, mainly due to an increased collagen
      related stiffness, compared with TAV patients. The increased wall stiffness in
      BAV patients may contribute to the higher prevalence for TAAs in this group.

PMID- 24881865
TI  - Genetic variations of MMP9 gene and intracerebral hemorrhage outcome: a cohort
      study in Chinese Han population.
AB  - OBJECTIVE: To investigate the association between genetic variations of matrix
      metalloproteinase 9 (MMP9) gene and intracerebral hemorrhage (ICH) outcome in
      Chinese Han population. METHODS: The clinical data and peripheral blood samples
      from the patients with ICH were collected. The patients were followed up for 3
      months, and poor outcome was defined as death or dependency (modified Rankin
      scale score of 3-6). MassARRAY Analyser was used to genotype the tagger single
      nucleotide polymorphisms (SNPs) of MMP9 gene. Construction of haplotypes and
      genetic comparisons were performed by employing PLINK 1.0.7 software. RESULTS:
      181 patients with ICH were recruited between September 2009 and October 2010.
      Information on genetic variations and follow-up assessments were available for
      169 (93.4%) patients. Independent patients at 90 days were younger than those who
      died or dependent (57.82 +/- 13.47 vs. 66.99 +/- 11.49 years, p<0.01). In
      addition, independent patients had lower National Institutes of Health Stroke
      Scale (NIHSS) score (4[1-6] vs. 13[9-19], p<0.01). There were no significant
      associations (all p>0.05) between MMP9 genetic variations (alleles, genotypes and
      haplotypes) and ICH outcome after adjustment for conventional risk factors.
      CONCLUSIONS: The genetic variations of MMP9 gene were not significantly
      associated with ICH outcome at 90 days in Chinese Han population.

PMID- 24881866
TI  - Parkinsonism in early Creutzfeldt-Jacob disease: possible pre- and post-synaptic
      mechanism.

PMID- 24881867
TI  - Predictive markers of disease evolution after a CIS in everyday practice.
AB  - Clinically isolated syndromes (CIS) indicate the possibility of developing
      multiple sclerosis (MS) over time in approximately 20-85% of the cases. Thus,
      accurately identifying which patients will present a second demyelinating episode
      and determining the degree of disability they could develop over the mid- to long
      term is considered crucial for a more individualized treatment. For this reason,
      a number of prognostic markers have been studied in an attempt to identify those
      that could provide additional information about the disease course. This review
      focuses only on markers with proven predictive power in CIS patients in the
      everyday clinical practice. In general, markers of conversion to clinically
      definite MS (CDMS) are more robust than those available for disability
      progression. More specifically, magnetic resonance imaging is, to this day, the
      most powerful tool for predicting both conversion to CDMS and disability
      progression in the mid-term. Other useful markers include the age of onset and
      the presence of oligoclonal bands in cerebrospinal fluid. Identifying a practical
      marker that improves the prognostic value of the available tools remains an unmet
      need. 

PMID- 24881868
TI  - Self-renewal and cell lineage differentiation strategies in human embryonic stem
      cells and induced pluripotent stem cells.
AB  - INTRODUCTION: Since the initial discoveries of human embryonic and induced
      pluripotent stem cells, many strategies have been developed to utilize the
      potential of these cells for translational research and disease modeling. The
      success of these aims and the development of future applications in this area
      will depend on the ability to generate high-quality and large numbers of
      differentiated cell types that genetically, epigenetically, and functionally
      mimic the cells found in the body. AREAS COVERED: In this review, we highlight
      the current strategies used to maintain stem cell pluripotency (a measure of stem
      cell quality), as well as provide an overview of the various differentiation
      strategies being used to generate cells from all three germ lineages. We also
      discuss the particular considerations that must be addressed when utilizing these
      cells for translational therapy, and provide an example of a cell type currently
      used in clinical trials. EXPERT OPINION: The major challenge in regenerative
      medicine and disease modeling will be in generating functional cells of
      sufficient quality that are physiologically and epigenetically similar to the
      diverse cells that they are modeled after. By meeting these criteria, these
      differentiated products can be successfully used in disease modeling,
      drug/toxicology screens, and cellular replacement therapy.

PMID- 24881869
TI  - Introducing mixed-charge copolymers as wound dressing biomaterials.
AB  - Herein, a pseudozwitterionic structure bearing moieties with mixed positive and
      negative charges is introduced to develop a potential biomaterial for wound
      dressing applications. New mixed-charge matrices were prepared by
      copolymerization of the negatively charged 3-sulfopropyl methacrylate (SA) and
      positively charged [2-(methacryloyloxy)ethyl] trimethylammonium (TMA) onto
      expanded polytetrafluoroethylene (ePTFE) membranes. The charge balance was
      effectively regulated through the control of the initial SA/TMA ratio. The focus
      was then laid on the assessment of a variety of essential properties of efficient
      wound dressings including, hydration property, resistance to fibrinogen
      adsorption, hemocompatibility, as well as resistance to fibroblast attachment and
      bacteria colonization. It was found that the pseudozwitterionic membranes,
      compared to those with charge bias in the poly(SA-co-TMA) structure, exhibited
      the best combination of major properties. Therefore, they were further tested for
      wound healing. Histological examination of mouse wound treated with the
      pseudozwitterionic membranes exhibited complete re-epithelialization and total
      formation of new connective tissues after 14 days, even leading to faster healing
      than using commercial dressing. Results presented in this work suggest that the
      mixed-charge copolymers with a perfect balance of positive and negative moieties
      represent the newest generation of biomaterials for wound dressings. 

PMID- 24881870
TI  - Characterization of murine pituitary-derived cell lines Tpit/F1, Tpit/E and
      TtT/GF.
AB  - The pituitary is an important endocrine tissue of the vertebrate that produces
      and secretes many hormones. Accumulating data suggest that several types of cells
      compose the pituitary, and there is growing interest in elucidating the origin of
      these cell types and their roles in pituitary organogenesis. Therein, the
      histogenous cell line is an extremely valuable experimental tool for
      investigating the function of derived tissue. In this study, we compared gene
      expression profiles by microarray analysis and real-time PCR for murine pituitary
      tumor-derived non-hormone-producing cell lines TtT/GF, Tpit/F1 and Tpit/E.
      Several genes are characteristically expressed in each cell line: Abcg2, Nestin,
      Prrx1, Prrx2, CD34, Eng, Cspg4 (Ng2), S100beta and nNos in TtT/GF; Cxcl12,
      Raldh1, Msx1 and Twist1 in Tpit/F1; and Cxadr, Sox9, Cdh1, EpCAM and Krt8 in
      Tpit/E. Ultimately, we came to the following conclusions: TtT/GF cells show the
      most differentiated state, and may have some properties of the pituitary vascular
      endothelial cell and/or pericyte. Tpit/F1 cells show the epithelial and
      mesenchymal phenotypes with stemness still in a transiting state. Tpit/E cells
      have a phenotype of epithelial cells and are the most immature cells in the
      progression of differentiation or in the initial endothelial-mesenchymal
      transition (EMT). Thus, these three cell lines must be useful model cell lines
      for investigating pituitary stem/progenitor cells as well as organogenesis. 

PMID- 24881871
TI  - Expression of Kruppel-like factor 6, KLF6, in rat pituitary stem/progenitor cells
      and its regulation of the PRRX2 gene.
AB  - Paired-related transcription factors, PRRX1 and PRRX2, which are present in
      mesenchymal tissues and participate in mesenchymal cell differentiation, were
      recently found in the stem/progenitor cells of the pituitary gland of ectodermal
      origin. To clarify the role of PRRX1 and PRRX2 in the pituitary gland, the
      present study first aimed to identify transcription factors that regulate Prrx1
      and Prrx2 expression. A promoter assay for the upstream regions of both genes was
      performed by co-transfection of the expression vector of several transcription
      factors, many of which are frequently found in the pituitary stem/progenitor
      cells. The results for the promoter activity of both genes showed expression in a
      cell type-dependent manner. Comprehensive comparison of transcriptional activity
      of several transcription factors was performed with CHO cells, which do not show
      Prrx1 and Prrx2 expression, and the results revealed the presence of common and
      distinct factors for both genes. Among them, KLF6 showed specific and remarkable
      stimulation of Prrx2 expression. In vitro experiments using an electrophoretic
      mobility shift assay and siRNA interference revealed a potential ability for
      regulation of Prrx2 expression by KLF6. Finally, immunohistochemistry confirmed
      the presence of KLF6 in the SOX2/PRRX2 double-positive stem/progenitor cells of
      the postnatal pituitary gland. Thus, the finding of KLF6 might provide a novel
      clue to clarify the maintenance of stem/progenitor cells of the postnatal
      pituitary gland. 

PMID- 24881872
TI  - P selectin and T cell profiles provide verification to understand the
      pathogenesis of liver cirrhosis in HCV and Schistosoma mansoni infections.
AB  - Hepatitis C virus (HCV) and Schistosoma mansoni are two major causes of chronic
      liver disease (CLD). Both immune alteration and thrombocytopenia are common
      complications in the majority of cirrhotic patients. The current study aimed to
      monitor the effect of T cell profile and platelets activation on the pathogenesis
      of liver cirrhosis in patients suffered from single or concomitant
      schistosomiasis and HCV infections. The subjects were divided into 4 groups:
      Group I, patients infected with schistosomiasis; Group II, patients infected with
      HCV; Group III, patients with combined liver diseases and Group IV: healthy
      individuals. All groups were subjected to full clinical evaluation as well as
      laboratory examination including ELISA anti-HCV antibodies screening,
      parasitological examination, and complete blood picture as well as flow cytometry
      for CD41, CD42, CD62P (P selectin), CD63, CD4 and CD8. The platelets count was
      significantly decreased in HCV and/or schistosoma infected patients compared to
      controls. The percentage of the total T-lymphocytes and T-helper was
      significantly reduced in all infected groups, while the percentage of T-cytotoxic
      was increased. The patients possessed a significantly higher percentage of the
      platelets activation markers than control group. There were considerable
      correlations between the platelets counts and P selectin and MFI.
      Thrombocytopenia was a common finding in patients with CLD. Patients with CLD
      showed increased platelets activation which may contribute to the occurrence of
      thrombocytopenia and play a role in the pathogenesis of CLD. Infected patient
      showed reduction in the cell-mediated-immunity as evidenced by low T -helper
      cells.

PMID- 24881873
TI  - Chronic caffeine ingestion causes microglia activation, but not proliferation in
      the healthy brain.
AB  - Caffeine is the most popular psychoactive drug in the world which contributes to
      behavioral and metabolic changes when ingested. Within the central nervous system
      (CNS), caffeine has a high affinity for A1 and A2a adenosine receptors. Serving
      as an antagonist, caffeine affects the ability of adenosine to bind to these
      receptors. Caffeine has been shown to alter neuronal functioning through
      increasing spontaneous firing. However, the effects of caffeine on non-neuronal
      cells in the CNS have not been studied extensively. Microglia are one phenotype
      of non-neuronal glia within the CNS. Acting as phagocytes, they contribute to the
      immune defense system of the brain and express A1 and A2a adenosine receptors.
      Caffeine, therefore, may affect microglia. In order to test this hypothesis, CD-1
      mice were randomly placed into one of three groups: control, low caffeine (0.3
      g/L water) and high caffeine (1.0 g/L water) and were allowed to drink freely for
      30 days. Following 30 days, brain sections were stained to reveal microglia.
      Morphological reconstructions and density measurements were examined in cortical
      and subcortical areas including the primary sensory cortex, primary motor cortex
      and striatum. Results indicate that microglial density throughout the brain is
      decreased in the caffeine groups as compared to the control. Caffeine also
      impacted microglia morphology shortening process length and decreasing branching.
      These results suggest that chronic caffeine ingestion has a systemic impact on
      microglia density and their activation.

PMID- 24881875
TI  - Protein delivery to vacuole requires SAND protein-dependent Rab GTPase conversion
      for MVB-vacuole fusion.
AB  - Plasma-membrane proteins such as ligand-binding receptor kinases, ion channels,
      or nutrient transporters are turned over by targeting to a lytic compartment-
      lysosome or vacuole--for degradation. After their internalization, these proteins
      arrive at an early endosome, which then matures into a late endosome with
      intraluminal vesicles (multivesicular body, MVB) before fusing with the
      lysosome/vacuole in animals or yeast. The endosomal maturation step involves a
      SAND family protein mediating Rab5-to-Rab7 GTPase conversion. Vacuolar
      trafficking is much less well understood in plants. Here we analyze the role of
      the single-copy SAND gene of Arabidopsis. In contrast to its animal or yeast
      counterpart, Arabidopsis SAND protein is not required for early-to-late endosomal
      maturation, although its role in mediating Rab5-to-Rab7 conversion is conserved.
      Instead, Arabidopsis SAND protein is essential for the subsequent fusion of MVBs
      with the vacuole. The inability of sand mutant to mediate MVB-vacuole fusion is
      not caused by the continued Rab5 activity but rather reflects the failure to
      activate Rab7. In conclusion, regarding the endosomal passage of cargo proteins
      for degradation, a major difference between plants and nonplant organisms might
      result from the relative timing of endosomal maturation and SAND-dependent Rab
      GTPase conversion as a prerequisite for the fusion of late endosomes/MVBs with
      the lysosome/vacuole.

PMID- 24881874
TI  - Transcriptional regulation by Pho23 modulates the frequency of autophagosome
      formation.
AB  - BACKGROUND: Autophagy as a conserved lysosomal/vacuolar degradation and recycling
      pathway is important in normal development and physiology, and defects in this
      process are linked to many kinds of disease. Because too much or too little
      autophagy can be detrimental, the process must be tightly regulated both
      temporally and in magnitude. Two parameters that affect this regulation are the
      size and the number of autophagosomes; however, although we know that the amount
      of Atg8 affects the size of autophagosomes, the mechanism for regulating their
      number has not been elucidated. The transcriptional induction and repression of
      the autophagy-related (ATG) genes is one crucial aspect of autophagy regulation,
      but the transcriptional regulators that modulate autophagy are not well
      characterized. RESULTS: We detected increased expression levels of ATG genes, and
      elevated autophagy activity, in cells lacking the transcriptional regulator
      Pho23. Using transmission electron microscopy, we found that PHO23 null mutant
      cells contain significantly more autophagosomes than the wild-type. By RNA
      sequencing transcriptome profiling, we identified ATG9 as one of the key targets
      of Pho23, and our studies with strains expressing modulated levels of Atg9 show
      that the amount of this protein directly correlates with the frequency of
      autophagosome formation and the level of autophagy activity. CONCLUSIONS: Our
      results identified Pho23 as a master transcriptional repressor for autophagy that
      regulates the frequency of autophagosome formation through its negative
      regulation of ATG9.

PMID- 24881876
TI  - Role of the primate ventral tegmental area in reinforcement and motivation.
AB  - Monkey electrophysiology suggests that the activity of the ventral tegmental area
      (VTA) helps regulate reinforcement learning and motivated behavior, in part by
      broadcasting prediction error signals throughout the reward system. However,
      electrophysiological studies do not allow causal inferences regarding the
      activity of VTA neurons with respect to these processes because they require
      artificial manipulation of neuronal firing. Rodent studies fulfilled this
      requirement by demonstrating that electrical and optogenetic VTA stimulation can
      induce learning and modulate downstream structures. Still, the primate dopamine
      system has diverged significantly from that of rodents, exhibiting greatly
      expanded and uniquely distributed cortical and subcortical innervation patterns.
      Here, we bridge the gap between rodent perturbation studies and monkey
      electrophysiology using chronic electrical microstimulation of macaque VTA (VTA
      EM). VTA-EM was found to reinforce cue selection in an operant task and to
      motivate future cue selection using a Pavlovian paradigm. Moreover, by combining
      VTA-EM with concurrent fMRI, we demonstrated that VTA-EM increased fMRI activity
      throughout most of the dopaminergic reward system. These results establish a
      causative role for primate VTA in regulating stimulus-specific reinforcement and
      motivation as well as in modulating activity throughout the reward system.

PMID- 24881877
TI  - Resolution mediator chemerin15 reprograms the wound microenvironment to promote
      repair and reduce scarring.
AB  - Disorders of cutaneous repair can cause disability or death given that skin
      functions as a protective barrier against the external environment. The
      inflammatory response triggered by tissue damage is thought to play both positive
      (e.g., pathogen-killing) and negative (e.g., scarring) roles in repair.
      Inflammatory resolution mediators such as chemerin15 (C15) control the magnitude
      and duration of the inflammatory response; however, their role in wound repair
      and scarring is unknown. Here, we show that the C15 precursor, chemerin, and its
      receptor, ChemR23, are both upregulated after skin damage and that the receptor
      is expressed by macrophages, neutrophils, and keratinocytes. Dynamic live-imaging
      studies of murine cutaneous wounds demonstrate that C15 delivery dampens the
      immediate intravascular inflammatory events, including platelet adhesion to
      neutrophils, an important event in driving leukocyte recruitment. C15
      administration indirectly accelerates wound closure while altering fibroblast
      mediated collagen deposition and alignment to reduce scarring. Macrophage
      recruitment is restricted to the immediate wound site rather than spilling
      extensively into the adjacent tissue as in control wounds, and macrophage
      phenotype in C15-treated wounds is skewed toward a less inflammatory phenotype
      with reduced iNOS, increased Arginase-1, and lower wound tumor necrosis factor
      alpha (TNF-alpha) expression. Modulation of inflammatory resolution pathways in
      acute and chronic wounds may therefore provide a novel therapeutic avenue to
      improve repair and reduce scarring.

PMID- 24881878
TI  - Plant vacuolar trafficking occurs through distinctly regulated pathways.
AB  - The multifunctional vacuole is the largest organelle in plant cells, and many
      proteins are transported to and stored in this organelle; thus, the vacuole has
      great physiological and agronomical importance. However, the molecular mechanism
      and regulation of plant vacuolar traffic remain largely unknown. In this study,
      we demonstrate that multiple vacuolar trafficking pathways operate in plants.
      RAB5 and RAB7 are evolutionarily conserved subfamilies of Rab GTPase, whose
      animal and yeast counterparts regulate vacuolar/endosomal trafficking in a
      sequential manner. Functional analyses of a putative activating complex for RAB7
      indicated that this complex is responsible for maturation from RAB5- to RAB7
      positive endosomes in plant cells. Moreover, these machinery components are
      recruited to a more complex trafficking network. Mutations in RAB5 and RAB7
      conferred counteracting effects on the vti11 mutant. Furthermore, impairment of
      RAB5- and RAB7-dependent pathways differentially affected the transport of
      distinctive cargos. These results indicate that plants have developed a complex
      vacuolar transport system distinct from that of nonplant systems by assigning
      evolutionarily conserved machinery to unique trafficking pathways. These pathways
      provide a fundamental basis for plant development at the cellular and higher
      ordered levels.

PMID- 24881880
TI  - Rapid convergent evolution in wild crickets.
AB  - The earliest stages of convergent evolution are difficult to observe in the wild,
      limiting our understanding of the incipient genomic architecture underlying
      convergent phenotypes. To address this, we capitalized on a novel trait,
      flatwing, that arose and proliferated at the start of the 21st century in a
      population of field crickets (Teleogryllus oceanicus) on the Hawaiian island of
      Kauai. Flatwing erases sound-producing structures on male forewings. Mutant males
      cannot sing to attract females, but they are protected from fatal attack by an
      acoustically orienting parasitoid fly (Ormia ochracea). Two years later, the
      silent morph appeared on the neighboring island of Oahu. We tested two hypotheses
      for the evolutionary origin of flatwings in Hawaii: (1) that the silent morph
      originated on Kauai and subsequently introgressed into Oahu and (2) that flatwing
      originated independently on each island. Morphometric analysis of male wings
      revealed that Kauai flatwings almost completely lack typical derived structures,
      whereas Oahu flatwings retain noticeably more wild-type wing venation. Using
      standard genetic crosses, we confirmed that the mutation segregates as a single
      locus, sex-linked Mendelian trait on both islands. However, genome-wide scans
      using RAD-seq recovered almost completely distinct markers linked with flatwing
      on each island. The patterns of allelic association with flatwing on either
      island reveal different genomic architectures consistent with the timing of two
      mutational events on the X chromosome. Divergent wing morphologies linked to
      different loci thus cause identical behavioral outcomes--silence--illustrating
      the power of selection to rapidly shape convergent adaptations from distinct
      genomic starting points.

PMID- 24881881
TI  - Dual responsive supramolecular amphiphiles: guest molecules dictate the
      architecture of pyridinium-tailored anthracene assemblies.
AB  - By introducing an electron-deficient guest molecule and a counter anion, the
      assembly morphology of 1-[11-(2-anthracenylmethoxy)-11-oxoundecyl]pyridinium
      bromide (2-AP) was transformed to microsheets and nanofibers from microtubes,
      respectively.

PMID- 24881879
TI  - Differential adhesion determines the organization of synaptic fascicles in the
      Drosophila visual system.
AB  - BACKGROUND: Neuronal circuits in worms, flies, and mammals are organized so as to
      minimize wiring length for a functional number of synaptic connections, a
      phenomenon called wiring optimization. However, the molecular mechanisms that
      establish optimal wiring during development are unknown. We addressed this
      question by studying the role of N-cadherin in the development of optimally wired
      neurite fascicles in the peripheral visual system of Drosophila. RESULTS:
      Photoreceptor axons surround the dendrites of their postsynaptic targets, called
      lamina cells, within a concentric fascicle called a cartridge. N-cadherin is
      expressed at higher levels in lamina cells than in photoreceptors, and all
      genetic manipulations that invert these relative differences displace lamina
      cells to the periphery and relocate photoreceptor axon terminals into the center.
      CONCLUSIONS: Differential expression of a single cadherin is both necessary and
      sufficient to determine cartridge structure because it positions the most
      adhesive elements that make the most synapses at the core and the less-adhesive
      elements that make fewer synapses at the periphery. These results suggest a
      general model by which differential adhesion can be utilized to determine the
      relative positions of axons and dendrites to establish optimal wiring.

PMID- 24881882
TI  - Aqueous Fe2S2 cluster: structure, magnetic coupling, and hydration behaviour from
      Hubbard U density functional theory.
AB  - We present a DFT + U investigation of the all-ferrous Fe2S2 cluster in aqueous
      solution. We determine the value of U by tuning the geometry of the cluster in
      the gas-phase to that obtained by the highly accurate CCSD(T) method. When the
      optimised value of U is employed for the aqueous Fe2S2 cluster (Fe2S2(aq)), the
      resulting geometry agrees well with the X-ray diffraction structure, while the
      magnetic coupling is in line with the estimate from Mossbauer data. Molecular
      dynamics trajectories predict Fe2S2(aq) to be stable in water, regardless of the
      introduction of U. However, significant differences arise in the geometry,
      hydration, and exchange constant of the solvated clusters. 

PMID- 24881883
TI  - Sensitivity of housekeeping genes in the suprachiasmatic nucleus of the mouse
      brain to diet and the daily light-dark cycle.
AB  - The endogenous timing system within the suprachiasmatic nuclei (SCN) of the
      hypothalamus drives the cyclic expression of the clock molecules across the 24h
      day-night cycle controlling downstream molecular pathways and physiological
      processes. The developing fetal clock system is sensitive to the environment and
      physiology of the pregnant mother and as such disruption of this system could
      lead to altered physiology in the offspring. Characterizing the gene profiles of
      the endogenous molecular clock system by quantitative reverse transcription
      polymerase chain reaction is dependent on normalization by appropriate
      housekeeping genes (HKGs). However, many HKGs commonly used as internal controls,
      although stably expressed under control conditions, can vary significantly in
      their expression under certain experimental conditions. Here we analyzed the
      expression of 10 classic HKG across the 24h light-dark cycle in the SCN of mouse
      offspring exposed to normal chow or a high fat diet during early development and
      in postnatal life. We found that the HKGs glyceraldehyde-3-phosphate
      dehydrogenase, beta actin and adenosine triphosphate synthase subunit to be the
      most stably expressed genes in the SCN regardless of diet or time within the 24h
      light-dark cycle, and are therefore suitable to be used as internal controls.
      However SCN samples collected during the light and dark periods did show
      differences in expression and as such the timing of collection should be
      considered when carrying out gene expression studies. 

PMID- 24881884
TI  - Functional network organizations of two contrasting temperament groups in
      dimensions of novelty seeking and harm avoidance.
AB  - Novelty seeking (NS) and harm avoidance (HA) are two major dimensions of
      temperament in Cloninger's neurobiological model of personality. Previous
      neurofunctional and biological studies on temperament dimensions of HA and NS
      suggested that the temperamental traits have significant correlations with
      cortical and subcortical brain regions. However, no study to date has
      investigated the functional network modular organization as a function of the
      temperament dimension. The temperament dimensions were originally proposed to be
      independent of one another. However, a meta-analysis based on 16 published
      articles found a significant negative correlation between HA and NS (Miettunen et
      al., 2008). Based on this negative correlation, the current study revealed the
      whole-brain connectivity modular architecture for two contrasting temperament
      groups. The k-means clustering algorithm, with the temperamental traits of HA and
      NS as an input, was applied to divide the 40 subjects into two temperament
      groups: 'high HA and low NS' versus 'low HA and high NS'. Using the graph
      theoretical framework, we found a functional segregation of whole brain network
      architectures derived from resting-state functional MRI. In the 'high HA and low
      NS' group, the regulatory brain regions, such as the prefrontal cortex (PFC), are
      clustered together with the limbic system. In the 'low HA and high NS' group,
      however, brain regions lying on the dopaminergic pathways, such as the PFC and
      basal ganglia, are partitioned together. These findings suggest that the neural
      basis of inhibited, passive, and inactive behaviors in the 'high HA and low NS'
      group was derived from the increased network associations between the PFC and
      limbic clusters. In addition, supporting evidence of topological differences
      between the two temperament groups was found by analyzing the functional
      connectivity density and gray matter volume, and by computing the relationships
      between the morphometry and function of the brain.

PMID- 24881885
TI  - Role of the mitochondrial Ca2+ uniporter in Pb2+-induced oxidative stress in
      human neuroblastoma cells.
AB  - Lead (Pb(2+)) has been shown to induce cellular oxidative stress, which is linked
      to changes in intracellular calcium (Ca(2+)) concentration. The mitochondrial
      Ca(2+) uniporter (MCU) participates in the maintenance of Ca(2+) homeostasis in
      neurons, but its role in Pb(2+)-induced oxidative stress is unclear. To address
      this question, oxidative stress was induced in human neuroblastoma SH-SY5Y cells
      and in newborn rats by Pb(2+) treatment. The results showed that the production
      of reactive oxygen species is increased in cells upon treatment with Pb(2+) in a
      dose-dependent manner, while glutathione and MCU expression were reduced.
      Moreover, neuronal nitric oxide synthase protein expression was elevated in rats
      exposed to Pb(2+) during gestation, while MCU expression was decreased.
      Application of the MCU activator spermine or MCU overexpression reversed Pb(2+)
      induced oxidative stress and inhibition of mitochondrial Ca(2+) uptake, while the
      MCU inhibitor Ru360 and MCU knockdown potentiated the effects of Pb(2+). These
      results indicate that the MCU mediates the Pb(2+)-induced oxidative stress
      response in neurons through the regulation of mitochondrial Ca(2+) influx. 

PMID- 24881887
TI  - Front-loading with clopidogrel plus aspirin followed by dual antiplatelet therapy
      in the prevention of early stroke recurrence.
AB  - Dual antiplatelet therapy with aspirin plus clopidogrel is not recommended for
      secondary stroke prevention because of lack of effectiveness and increased
      hemorrhagic risk. Recent studies show that in patients with a very recent
      transient ischemic attack or minor ischemic stroke loading with 300 mg
      clopidogrel plus aspirin, followed by clopidogrel 75 mg plus aspirin once daily
      for up to 90 days significantly decreases the rate of recurrent stroke,
      especially strokes that occur within few days from the event that led to medical
      attention, without an increase in severe bleedings. This article reviews the
      pharmacokinetics and pharmacodynamics of clopidogrel, focusing on loading doses,
      and summarizes the results of the studies that have shown the effectiveness of
      the front-loading approach in the early secondary prevention of stroke. 

PMID- 24881886
TI  - ASMT gene expression correlates with cognitive impairment in patients with
      recurrent depressive disorder.
AB  - BACKGROUND: Recurrent depressive disorder is a multifactorial disease; one of the
      typical features is cognitive impairment. The purpose of this study was analysis
      of ASMT gene expression both on mRNA and protein levels in patients with
      recurrent depressive disorder (rDD) and assessment of the relationship between
      plasma level of ASMT protein, gene expression on mRNA level, and cognitive
      performance. MATERIAL AND METHODS: The study included 236 subjects: patients with
      rDD (n=131) and healthy subjects (n=105, CG). Cognitive function assessment was
      based on: Trail Making Test, The Stroop Test, Verbal Fluency Test (VFT), and
      Auditory Verbal Learning Test (AVLT). RESULTS: Both mRNA and protein expression
      levels of ASMT gene were significantly higher in healthy subjects when compared
      to rDD. The average ASMT mRNA expression level measured for the entire group was
      M=0.21 (SD=0.09), and the protein level was M=12.84 (SD=3.29). In patients with
      rDD, statistically significant correlations occurred between both mRNA and
      protein expression levels and part A of the TMT (negative correlation) and verbal
      fluency test (positive correlation). In the group CG, there was no statistically
      significant association between the analyzed variables. In the entire group there
      was a statistically significant correlation between both ASMT mRNA and protein
      expression levels and all the neuropsychological tests used in the survey.
      CONCLUSIONS: 1. Our study confirms previous results showing decreased mRNA and
      protein expression levels of ASMT gene in depression. 2. Our data suggest a
      relationship between decreased mRNA and protein expression levels of ASMT gene
      and cognitive impairment.

PMID- 24881888
TI  - Quality of life in dementia: a systematically conducted narrative review of
      dementia-specific measurement scales.
AB  - OBJECTIVES: Ascertaining the quality of life (QoL) in people with dementia is
      important for evaluating service outcomes and cost-effectiveness. This paper
      identifies QoL measures for people with dementia and assesses their properties.
      METHOD: A systematic narrative review identified articles using dementia QoL
      measures. Electronic databases searched were AMED, CINAHL, EMBASE, Index to
      Theses, IBSS, MEDLINE, PsycINFO, Sociological Abstracts, and Web of Science. All
      available years and languages (if with an English language abstract) were
      included. RESULTS: Searches yielded 6806 citations; 3043 were multiple duplicates
      (759 being true duplicates). Abstracts were read; 182 full papers were
      selected/obtained, of which 126 were included as relevant. Few measures were
      based on rigorous conceptual frameworks. Some referenced Lawton's model (Dementia
      Quality of Life [DQOL] and Quality of Life in Alzheimer's Disease [QOL-AD]),
      though these tapped part of this only; others claimed relationship to a health
      related QoL concept (e.g. DEMQOL), though had less social relevance; others were
      based on limited domains (e.g. activity, affect) or clinical opinions (Quality of
      Life in Late-Stage Dementia [QUALID]). Many measures were based on proxy
      assessments or observations of people with dementia's QoL, rather than their own
      ratings. The Bath Assessment of Subjective Quality of Life in Dementia (BASQID)
      was developed involving people with dementia and caregivers, but excluded some of
      their main themes. All measures were tested on selective samples only (ranging
      from community to hospital clinics, or subsamples/waves of existing population
      surveys), in a few sites. Their general applicability remains unknown, and
      predictive validity remains largely untested. CONCLUSION: The lack of consensus
      on measuring QoL in dementia suggests a need for a broader, more rigorously
      tested QoL measure.

PMID- 24881889
TI  - Sudden cardiac death in a dialysis patient: hyperkalemia reconsidered.
AB  - BACKGROUND: To many physicians, hyperkalemia is the first diagnosis ascribed to
      any patient with end-stage renal disease and abnormal electrocardiographic
      morphologies or dysrhythmias. CASE REPORT: A 52-year-old man with end-stage renal
      disease presented in cardiac arrest. The patient was initially presumed to have
      hyperkalemia, based on the appearance of wide QRS complexes on the monitor. The
      diagnosis of hyperkalemia was incorrect; the patient was severely hypokalemic and
      suffered recurrent episodes of ventricular fibrillation and torsades de pointes.
      WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS: An emergency physician's
      differential diagnosis of sudden cardiac arrest in the patient with end-stage
      renal disease should not be limited to hyperkalemia and myocardial infarction.
      Hypokalemia should also be considered. Hypokalemia may be an under-recognized
      cause of sudden cardiac death in this patient population.

PMID- 24881890
TI  - Anaphylaxis.
AB  - BACKGROUND: Anaphylaxis is the quintessential critical illness in emergency
      medicine. Symptoms are rapid in onset and death can occur within minutes.
      Approximately 1500 patients die annually in the United States from this deadly
      disorder. It is imperative, therefore, that emergency care providers be able to
      diagnose and appropriately treat patients with anaphylaxis. Any delays in
      recognition or initiation of therapy can result in unnecessary increases in
      patient morbidity and mortality. DISCUSSION: Recent literature, including updated
      international anaphylaxis guidelines, has improved our understanding and
      management of this critical illness. Anaphylaxis is a multisystem disorder that
      can manifest signs and symptoms related to the cutaneous, respiratory,
      cardiovascular, and gastrointestinal systems. Epinephrine remains the drug of
      choice and should initially be administered intramuscularly, into the
      anterolateral thigh, as soon as the diagnosis is suspected. For patients
      unresponsive to repeated intramuscular injections, a continuous infusion of
      epinephrine should be started. Antihistamines and corticosteroids are second-line
      medications and should never be given in lieu of, or prior to, epinephrine.
      Aggressive fluid resuscitation should also be used to treat the intravascular
      volume depletion characteristic of anaphylaxis. Patient observation and
      disposition should be individualized, as there is no well-defined period of
      observation after resolution of signs and symptoms. CONCLUSIONS: For patients
      with anaphylaxis, rapid and appropriate administration of epinephrine is critical
      for survival. Additional therapy, such as supplemental oxygen, intravenous
      fluids, antihistamines, and corticosteroids should not delay the administration
      of epinephrine.

PMID- 24881891
TI  - Understanding the value of emergency care: a framework incorporating stakeholder
      perspectives.
AB  - BACKGROUND: In the face of escalating spending, measuring and maximizing the
      value of health services has become an important focus of health reform. Recent
      initiatives aim to incentivize high-value care through provider and hospital
      payment reform, but the role of the emergency department (ED) remains poorly
      defined. OBJECTIVES: To achieve an improved understanding of the value of
      emergency care, we have developed a framework that incorporates the perspectives
      of stakeholders in the delivery of health services. METHODS: A pragmatic review
      of the literature informed the design of this framework to standardize the
      definition of value in emergency care and discuss outcomes and costs from
      different stakeholder perspectives. The viewpoint of patient, provider, payer,
      health system, and society is each used to assess value for emergency medical
      conditions. RESULTS: We found that the value attributed to emergency care differs
      substantially by stakeholder perspective. Potential targets to improve ED value
      may be aimed at improving outcomes or controlling costs, depending on the acuity
      of the clinical condition. CONCLUSION: The value of emergency care varies by
      perspective, and a better understanding is achieved when specific outcomes and
      costs can be identified, quantified, and measured. Using this framework can help
      stakeholders find common ground to prioritize which costs and outcomes to target
      for research, quality improvement efforts, and future health policy impacting
      emergency care.

PMID- 24881892
TI  - Night shifts in emergency medicine: the american board of emergency medicine
      longitudinal study of emergency physicians.
AB  - BACKGROUND: Night shift work is an integral component of the practice of
      emergency medicine (EM). Previous studies have demonstrated the challenges of
      night shift work to health and well being among health care providers. OBJECTIVE:
      This study was undertaken to describe the self-reported experience of emergency
      physicians regarding night shift work with respect to quality of life and career
      satisfaction. METHODS: The 2008 American Board of Emergency Medicine (ABEM)
      Longitudinal Study of Emergency Physicians (LSEP) was administered by mail to
      1003 ABEM diplomates. RESULTS: Among 819 participants in the 2008 LSEP Physician
      Survey, most participants responded that night shift work negatively influenced
      job satisfaction with a moderate or major negative influence (58%; n = 467/800).
      Forty-three percent of participants indicated that night shifts had caused them
      to think about leaving EM (n = 344/809). Most participants responded that working
      night shifts has had mild negative effects (51%; n = 407/800) or major negative
      effects (9%; n = 68) on their health. Respondents were asked to describe how
      working night shifts has affected their health. Common themes included fatigue
      (36%), poor quality of sleep (35%), mood decrement/irritability (29%), and health
      maintenance challenges (19%). Among participants in the 2008 LSEP Retired
      Physician Survey, night shifts were a factor in the decision to retire for 56% of
      participants. CONCLUSIONS: Emergency physicians report negative impacts of night
      shift work, including fatigue, poor quality of sleep, mood decrement,
      irritability, and health challenges. Night shifts have a negative influence on
      job satisfaction and can be a factor in the decision to retire.

PMID- 24881893
TI  - Ethical controversies surrounding the management of potential organ donors in the
      emergency department.
AB  - BACKGROUND: On a daily basis, emergency physicians are confronted by patients
      with devastating neurological injuries and insults. Some of these patients,
      despite our best efforts, will not survive. However, from these tragedies, there
      may be benefit given to others who are awaiting organ transplantation. Steps
      taken in the emergency department (ED) can be critical to preserving the option
      of organ donation in patients whose neurologic insult places them on a potential
      path to declaration of brain death. Much of the literature on this subject has
      focused on the utilitarian value of clinical interventions in the potential organ
      donor to optimize the likelihood of effective organ procurement. CASE
      PRESENTATION: In this article, we present an actual case that reveals additional
      ethical perspectives to consider in how emergency physicians manage patients in
      the ED who can be confidently predicted to progress to death, as attested by
      neurologic criteria, and become organ donors. The case involves a patient with a
      devastating, nonsurvivable intracerebral hemorrhage who rapidly progressed to
      hemodynamic instability. DISCUSSION: This case reveals how the current organ
      donor referral and maintenance system raises ethical tensions for emergency
      physicians and ED personnel. CONCLUSION: This process imposes limitations on
      communication with patient surrogate decision-makers while calling for
      interventions with the primary purpose of benefiting off-site patients awaiting
      transplantation.

PMID- 24881894
TI  - Organ donation and the emergency department: ethically appropriate and legally
      supported.

PMID- 24881895
TI  - Mixed-mode liquid chromatography coupled to tandem mass spectrometry for the
      analysis of aminoglycosides in meat.
AB  - A novel LC-MS/MS method has been developed for the determination of 13
      aminoglycoside antibiotics in meat products. Among the chromatographic columns
      tested, the mixed-mode Obelisc R provided the best performance. Electrospray has
      been used for the coupling of the LC and the effect of temperature on the
      ionization has been evaluated. The mass spectra of AGs have been studied in order
      to select the most adequate precursor and product ions for quantitation and
      confirmation in SRM mode, showing that the single charged [M+H](+) provided
      better precisions than the double charged [M+2H](2+). Accurate mass measurements
      have been performed in order to confirm the molecular composition of the product
      ions, allowing the establishment of a new mechanism for some product ions of STR
      and DHSTR. A sample treatment based on an extraction and a SPE clean-up has been
      applied to a wide variety of meat products such as frankfurters; sausages; and
      minced meat of pork, veal, and chicken. Method limits of quantitation in the low
      microgram per kilogram level (1-50 MUg kg(-1)), precisions %RSD below 15 % and
      accuracies expressed as relative errors below 23 % have been obtained, making the
      proposed method suitable for routine analysis.

PMID- 24881896
TI  - Ethical and educational considerations in coding hand surgeries.
AB  - PURPOSE: To assess treatment coding knowledge and practices among residents,
      fellows, and attending hand surgeons. METHODS: Through the use of 6 hypothetical
      cases, we developed a coding survey to assess coding knowledge and practices. We
      e-mailed this survey to residents, fellows, and attending hand surgeons. In
      additionally, we asked 2 professional coders to code these cases. RESULTS: A
      total of 71 participants completed the survey out of 134 people to whom the
      survey was sent (response rate = 53%). We observed marked disparity in codes
      chosen among surgeons and among professional coders. CONCLUSIONS: Results of this
      study indicate that coding knowledge, not just its ethical application, had a
      major role in coding procedures accurately. Surgical coding is an essential part
      of a hand surgeon's practice and is not well learned during residency or
      fellowship. Whereas ethical issues such as deliberate unbundling and upcoding may
      have a role in inaccurate coding, lack of knowledge among surgeons and coders has
      a major role as well. CLINICAL RELEVANCE: Coding has a critical role in every
      hand surgery practice. Inconstancies among those polled in this study reveal that
      an increase in education on coding during training and improvement in the clarity
      and consistency of the Current Procedural Terminology coding rules themselves are
      needed.

PMID- 24881897
TI  - An anatomical basis for endoscopic cubital tunnel release and associated clinical
      outcomes.
AB  - PURPOSE: To study the ulnar nerve in fresh-frozen cadavers as related to
      endoscopic release of the cubital tunnel and to present a retrospective review of
      patients treated with decompression via endoscopic visualization. METHODS: To
      further our understanding of relevant anatomy, we dissected 26 cadaver limbs. We
      paid special attention to fascial membranes as potential sites of constriction as
      well as the position of nerves, vessels, and aberrant anatomy. These findings
      facilitated our understanding of the extent of release in 80 patients (92 cases)
      with endoscopic cubital tunnel simple decompression. Outcome measures included
      Disabilities of the Arm, Shoulder, and Hand score, Gabel and Amadio score, and
      grip and pinch strengths. RESULTS: We noted fascial bands proximal to the medial
      epicondyle in 12 of 26 cadaver specimens, 2 of which could be the so-called
      arcade of Struthers. We observed a high degree of variability in the anatomy of
      the flexor pronator aponeurosis distal to the medial epicondyle. Where present (n
      = 10), medial antebrachial cutaneous nerve branches crossed the ulnar nerve at an
      average distance of 2.9 cm from the medial epicondyle (range, 1.0-4.5 cm).
      Aberrant structures were noted in 8 of the 26 specimens, including an anconeus
      epitrochlearis muscle in 2 specimens, a basilic vein crossing the ulnar nerve in
      4 specimens, and an accessory origin of the medial head of the triceps from the
      medial intermuscular septum in 2 specimens. In the clinical portion of this
      study, the average Disabilities of the Arm, Shoulder, and Hand score before
      surgery was 49 (n = 34) and after surgery was 25 (n = 56). The Gabel and Amadio
      outcome scores were 24 excellent, 40 good, 25 fair, and 3 poor (n = 92). Average
      follow-up was 8.2 months (range, 0.1-35 mo). CONCLUSIONS: Cadaveric dissections
      shed light on vulnerable anatomical structures during release, including branches
      of the medial antebrachial cutaneous nerve, ulnar nerve, brachial artery, fascial
      bands, and basilic vein. The high degree of anatomical variability in this study
      highlights the advantage of endoscopic visualization in allowing surgeons to
      minimize surgical trauma. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 24881898
TI  - The influence of patients' participation in research on their satisfaction.
AB  - PURPOSE: To determine if there was a difference between patients participating in
      research and those who did not regarding their satisfaction with the medical
      encounter and their physician. METHODS: We prospectively randomized 128 patients
      to either complete 20 minutes of questionnaires (participate in research) or not.
      After the visit, all patients rated their satisfaction with their visit and
      satisfaction with the doctor on an 11-point ordinal satisfaction scales, with 0
      being not at all satisfied and 10 being completely satisfied. Average
      satisfaction scores were analyzed in relation to demographics, questionnaires,
      and involvement in research. RESULTS: There were no significant differences
      between patients that did and did not participate in research for satisfaction
      with the medical encounter or satisfaction with the treating physician.
      Satisfaction was not associated with marital status, work status, or diagnosis.
      There was a significant correlation between greater satisfaction and both less
      education and lower self-efficacy. There was no significant correlation between
      patient satisfaction and magnitude of disability, pain intensity, or health
      anxiety. CONCLUSIONS: This study demonstrated that patients' participation in
      research can coexist with patient satisfaction. TYPE OF STUDY/LEVEL OF EVIDENCE:
      Prognostic I.

PMID- 24881899
TI  - Complications associated with operative versus nonsurgical treatment of distal
      radius fractures in patients aged 65 years and older.
AB  - PURPOSE: To compare complication rates for distal radius fractures treated
      operatively versus nonsurgical in patients older than 65 years. We hypothesized
      that surgical intervention would improve fracture alignment, but it would be
      associated with more complications and equivalent functional outcomes when
      compared with the nonsurgical group. METHODS: Patients (operative, n = 129) and
      controls (nonsurgical, n = 129) were identified from a prospective clinical and
      operating room database. They were matched on fracture severity (AO-A/B/C1 vs AO
      C2/C3), sex, age, and energy of injury. Data on complications were extracted from
      medical charts using a validated complications checklist, and radiologic data
      were collected for all patients. Functional outcomes (Patient-Related Wrist
      Evaluation) at 1 year were available in only a subset of patients. We determined
      differences in complication and reoperation rates using a chi-square test.
      RESULTS: A significant number of patients experienced complications in the
      operative group (operative = 37 of 129; nonsurgical = 22 of 129). The most common
      complication was median neuropathy (n = 8 operative; n = 14 nonsurgical),
      followed by surgical site infections (n = 16 operative; 12 of 16 were pin site
      infections) and complex regional pain syndrome (n = 4 operative; 3 nonsurgical).
      The complication rate in patients treated with volar plate was 22% (16 of 74),
      for dorsal plate it was 50% (2 of 4), for external fixation it was 42% (16 of
      38), and for percutaneous pinning it was 23% (3 of 13). The number of patients
      requiring reoperations was similar in both groups (11 [9%] operative; 7 [5%]
      nonsurgical). Our secondary radiologic and functional outcomes demonstrate that
      despite a higher incidence of malunion in nonsurgical patients (nonsurgical: 69%
      vs operative: 29%), a subset of patients from both groups (n = 140) had minimal
      pain and disability at 1 year (Patient-Related Wrist Evaluation operative: 16.9
      +/- 23.2; nonsurgical: 15.7 +/- 17.5). CONCLUSIONS: In a study matching fracture
      severity, sex, age, and energy of injury, we found that elderly patients with
      distal radius fractures who underwent surgery had higher complication rates than
      those treated nonsurgically. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic III.

PMID- 24881900
TI  - Adoptive immunotherapy for non-small cell lung cancer by NK and cytotoxic T
      lymphocytes mixed effector cells: retrospective clinical observation.
AB  - The objective of the current study was to retrospectively investigate the
      efficacy of adaptive transfer of natural killer (NK) and cytotoxic T lymphocytes
      mixed effector (NKTm) cells in non-small cell lung cancer (NSCLC) patients in
      comparison to a control group of NSCLC patients. NKTm cells were obtained by ex
      vivo expansion of peripheral blood mononuclear cells (PBMCs) of patients followed
      with phenotype determination. Primary end point was overall survival (OS). Ex
      vivo expansion caused significant enrichment of CD3(+), CD3(+)CD8(+), CD45RO(+),
      CD25(+), CD29(+) and CD3(+)CD16(+)/CD56(+) cells (P<0.05). The OS of the
      immunotherapy group was significantly longer than that of the control group and
      the risk of death decreased by 43.8% (31.1 months vs 18.1 months, P=0.008,
      HR=0.562, 95% CI 0.367-0.860). Two-year survival rate of patients in the
      immunotherapy group was better than in the control group (62.95% vs 35.44%,
      P<0.05). Gender, clinical stage, application of TKI, number of chemotherapy
      cycle, and application of NKTm immunotherapy were independent prognostic factors
      for NSCLC patients. The OS in subgroups of males, <60 years age, clinical stage
      IIIb+IV, no brain metastases, without radiotherapy, chemotherapy of >6 cycles, no
      application of TKI and TKI invalid was prolonged after NKTm cellular
      immunotherapy (P<0.05). Ex vivo expansion of NKTm cells was effective and had no
      adverse safety concerns, thus highlight that adaptive transfer of NKTm cells may
      prolong the OS of NSCLC patients and increase 2 year survival rate.

PMID- 24881901
TI  - Synergistic effect of intramolecular charge transfer toward supramolecular pKa
      shift in cucurbit[7]uril encapsulated coumarin dyes.
AB  - This article presents the process and mechanism of supramolecular pKa shift in
      two bichromophoric coumarin laser dyes, namely, coumarin 7 (C7), (DeltapK(a) =
      4.6) and coumarin 30 (C30), (DeltapK(a) = 3.0), achieved by introducing a
      synthetic macrocyclic receptor, cucurbit[7]uril (CB7), in aqueous media. The
      intramolecular charge transfer, from the diethylamino coumarin moiety toward the
      benzimidazolyl moiety and its protonation, even at pH ~8, is facilitated by the
      interaction of the cucurbituril host in a 2:1 (CB7/dye) stoichiometric ratio. The
      CB7 macrocycle interacts with C7/C30 dyes in a stepwise manner with binding
      constants of the order of K(1) ?10(5) M(-1), K2 ?10(4) M(-1) for both C7 and C30
      dyes. This study underlines a structure-property relationship to explain the host
      induced changes in the stereoelectronic distributions in the guest dyes
      supporting the supramolecular pK(a) shifts and is appropriately established by
      both experimental and theoretical considerations. On the other hand, the
      increased solubility (>250 times) and enhancement in fluorescence intensity (>13
      fold) of the coumarin dyes in the presence of CB7 also find applications for
      developing aqueous dye laser systems where this supramolecular strategy will
      largely suppress the disadvantages of low solubility, aggregation, lower
      emission, or low stability of the dye in aqueous medium.

PMID- 24881902
TI  - Coming to terms with early sports specialization and athletic injuries.
AB  - The body grows stronger and performs best when appropriate loads and activities
      are followed by appropriate physical and mental rest and recovery. With this
      understanding, one has to question the true value of developing a particular
      sport skill set during childhood and adolescence at the expense of early injury,
      burnout, and lack of coping-skill development.

PMID- 24881903
TI  - Osteochondroma fracture at the distal medial femur.
AB  - The patient was a 27-year-old man currently serving in the military who was
      evaluated by a physical therapist in a direct-access mode of care for a chief
      complaint of worsening left distal medial thigh pain. Given the traumatic
      mechanism of injury, worsening symptoms, and the presence of a painful, firm mass
      in the left distal medial thigh region, the physical therapist ordered
      radiographs of the left femur, which demonstrated a fracture at the base of an
      8.5-cm osteochondroma located at the distal medial femur.

PMID- 24881904
TI  - Altitude does not reduce concussion incidence in professional football players: a
      poor understanding of health statistics and altitude physiology.

PMID- 24881907
TI  - Lipoic acid and dihydrolipoic acid. A comprehensive theoretical study of their
      antioxidant activity supported by available experimental kinetic data.
AB  - The free radical scavenging activity of lipoic acid (LA) and dihydrolipoic acid
      (DHLA) has been studied in nonpolar and aqueous solutions, using the density
      functional theory and several oxygen centered radicals. It was found that lipoic
      acid is capable of scavenging only very reactive radicals, while the
      dehydrogenated form is an excellent scavenger via a hydrogen transfer mechanism.
      The environment plays an important role in the free radical scavenging activity
      of DHLA because in water it is deprotonated, and this enhances its activity. In
      particular, the reaction rate constant of DHLA in water with an HOO(*) radical is
      close to the diffusion limit. This has been explained on the basis of the strong
      H-bonding interactions found in the transition state, which involve the
      carboxylate moiety, and it might have implications for other biological systems
      in which this group is present. 

PMID- 24881908
TI  - Characterisation of the antibacterial effect of polyethyleneimine nanoparticles
      in relation to particle distribution in resin composite.
AB  - OBJECTIVES: To characterise the antibacterial effect of resin composite
      incorporating cross-linked quaternised polyethyleneimine (QPEI) nanoparticles in
      relation to their distribution in the bulk material. METHODS: The antibacterial
      effect of resin composite incorporating QPEI nanoparticle was tested against
      various oral pathogens, including Enterococcus faecalis, Streptococcus mutans,
      Actinomyces viscousus, Lactobacilus casei and whole saliva. Nanoparticle
      distribution in the modified resin composite was assessed using X-ray
      photoelectron spectroscopy (XPS). Additionally, the degree of conversion was
      recorded. RESULTS: Total bacterial inhibition was detected against all the tested
      pathogens following direct contact with the outer surface of the modified resin
      composite. Similarly, the inner surface of the modified resin composite caused
      total inhibition. Electron microscope images showed bacterial death. XPS revealed
      surface I(-) ions on both the outer and the inner surfaces of the modified
      composite. No I(-) ions were detected in the unmodified composite. Nanoparticle
      distribution was higher on the inner surface of the modified composite. The
      composite's degree of conversion was unaffected by nanoparticle addition.
      CONCLUSIONS: QPEI nanoparticles represent a new generation of antibacterial
      nanoparticles which are highly promising in preventing bacterial recontamination
      when restoring teeth.

PMID- 24881910
TI  - Endocrine surgery: current and future issues.

PMID- 24881909
TI  - Abolition of anti-adhesiogenic effect of heparin by protamine sulfate.
AB  - OBJECTIVE: Intraabdominal adhesion is a frequently encountered condition after
      surgery and can end up in important complications. The objective of this study is
      to test whether the antiadhesiogenic effect of heparin could be antagonized by
      administration of protamine in a rat model. MATERIAL AND METHODS: A laparotomy
      with caecal abrasion model was used in 40 Wistar rats. Single dose of 1 cc saline
      was injected subcutaneously (SC) in one group (control); 50 IU/kg heparin was
      injected SC in Group 2; 50 IU/kg protamine SC given to Group 3; 50 IU/kg heparin
      and 50 IU/kg protamine was given SC to Group 4 for 3 consecutive days. Each group
      consisted of 10 rats. All rats were sacrificed one week later for macroscopic and
      microscopic examination and they were scored for adhesion using Mazuji adhesion
      scale. RESULTS: There was significant difference in the heparin group with
      respect to Mazuji adhesion score, histopathological score (fibrosis, inflammation
      and vascular proliferation) and S-100 staining (P < 0.05). Additionally, the
      inflammation was more severe in the mucosa and submucosa compared to serosa in
      the heparin group (P < 0.01). With respect to fibrosis and vascular
      proliferation, apart from submucosal fibrosis, heparin group was statistically
      superior to the control group by means of each layer (P < 0.01). CONCLUSION: It
      seems that heparin is effective preventing adhesion in this rat model. Abolition
      of heparin's antiadhesiogenic effect by protamine administration is likely
      exerted via its antithrombine activity. Clinical application of our findings in
      intraabdominal surgery warrants further investigation.

PMID- 24881906
TI  - Nonarthritic hip joint pain.
AB  - The Orthopaedic Section of the American Physical Therapy Association (APTA) has
      an ongoing effort to create evidence-based practice guidelines for orthopaedic
      physical therapy management of patients with musculoskeletal impairments
      described in the World Health Organization's International Classification of
      Functioning, Disability, and Health (ICF). The purpose of these clinical practice
      guidelines is to describe the peer-reviewed literature and make recommendations
      related to nonarthritic hip joint pain.

PMID- 24881911
TI  - Primary giant hepatic neuroendocrine carcinoma: a case report.
AB  - Carcinoid tumours arise from neuroendocrine cells and may develop in almost any
      organ. These type of tumours actually are correctly termed neuroendocrine
      tumours. Hepatic neuroendocrine carcinomas rarely arise as primary tumour; in
      fact on 100 cases reported in literature just a few of these are of primary
      nature. We report the case of a giant hepatic neuroendocrine carcinoma in a 55
      year-old man. The symptoms were only recurrent hypoglycemia and an abdominal
      mass. Diagnosis was performed by blood analysis, ultrasonography, TC scan and
      In111-DTPA-octreotide scan. Surgical treatment occurred by an en bloc removal of
      the mass and a wide resection with free margins. Histological examination
      confirmed diagnosis. Clinical and instrumental diagnostic follow-up show the
      patient still alive, in very good conditions and disease free two years after
      surgery. 

PMID- 24881913
TI  - Predictive factors of successful treatment-free remission for patients with
      chronic myeloid leukemia.

PMID- 24881914
TI  - Management of chronic myeloid leukemia for Japanese patients in the era of TKIs.

PMID- 24881915
TI  - Gemtuzumab ozogamicin combined chemotherapy for elderly patients with acute
      myeloid leukemia.

PMID- 24881916
TI  - Clinical characteristics and functional assessment of elderly patients with
      cancer.

PMID- 24881917
TI  - Analysis of Japanese registration from the randomized international trial for
      childhood anaplastic large cell lymphoma (ALCL99-R1).
AB  - The randomized international trial for childhood anaplastic large cell lymphoma,
      (ALCL99-R1) involving European study groups and a Japanese group, compared six
      courses of methotrexate 1 g/m(2) over 24 hours with an intrathecal injection (IT)
      (MTX1 arm) with six courses of methotrexate 3 g/m(2) over 3 hours without IT
      (MTX3 arm). In this report, data from the Japanese portion of the trial are
      compared with the results of the international study. Overall, 352 patients were
      recruited for the international study, and 44 of these patients were from Japan.
      Median follow-up times were 3.8 and 3.5 years, respectively, in the international
      and Japanese studies. The two-year event-free and 2-year overall survival rates
      of the international study were 74% and 93%. The corresponding figures for those
      registered in Japan were 81% and 96%, respectively. Clinical characteristics and
      outcomes of patients were similar in the two groups. Incidences of grade 4
      hematologic toxicity, infection, and grade 3 to 4 stomatitis, which were reported
      to be statistically significantly higher after the MTX1 arm in the international
      study, were also statistically significantly higher after the MTX1 arm for those
      registered in Japan. Results of ALCL99-R1 treatment in Japan were essentially the
      same as in the international study. The international study is anticipated to
      contribute to establishing an optimal treatment for ALCL, a rare childhood
      lymphoma.

PMID- 24881918
TI  - Evaluation of clinical performance of the major BCR-ABL mRNA detection kit which
      enables conversion to international standard scale using the reference material
      calibrator.
AB  - In a multicenter study, we evaluated the Major BCR-ABL mRNA/ABL mRNA
      quantification kit (M135R), which uses reference material included in the kit
      designed to report results using the international scale (IS). In total, 127
      samples were studied. A good correlation was observed between M135R results and
      home-brew RT-qPCR results, which are reported on the IS using a conversion factor
      (r=0.90; n=115). However, the correlation coefficient between M135R results and
      Amp-CML results was relatively low (r=0.56; n=108). A good correlation was
      observed between M135R results from the two assay sites (r=0.94; n=115). The
      subset analysis of samples from the two assay sites showed M135R to have a good
      correlation even in the low IS range (r=0.98; IS<=1%). M135R showed high
      sensitivity and accuracy for detecting minimal residual disease and is considered
      to be a useful tool for treatment response assessment and for early detection of
      recurrence in CML patients.

PMID- 24881919
TI  - Congenital dysfibrinogenemia coincidentally diagnosed at the onset of chronic
      myelogenous leukemia.
AB  - A 34-year-old man was referred to our hospital for leukocytosis and fundal
      hemorrhage. Peripheral blood and coagulation tests showed increases in cells at
      all stages of the neutrophilic series and a low level of fibrinogen (Fbg).
      Chronic myelogenous leukemia (CML) was diagnosed, and nilotinib was administered.
      During the clinical course of CML treatment, plasma Fbg levels continued to be
      low, but the patient showed neither hemorrhagic nor thrombotic complications. Fbg
      analysis showed normal antigen levels and low activity levels, which indicated
      dysfibrinogenemia. Genetic analysis revealed a heterozygous gene mutation
      (gamma308AAT->AAG), a mutation which was also found in the patient's mother.
      Asymptomatic patients with dysfibrinogenemia have a low risk of hemorrhage in
      daily life and do not require treatment. However, in those undergoing major
      surgery or in serious accidents, replacement therapy may be required. When the
      cause of low Fbg levels is unknown, dysfibrinogenemia or fibrinogen deficiency
      should be considered. Even asymptomatic patients may benefit from more detailed
      immunologic and genetic analyses.

PMID- 24881920
TI  - Diffuse large B-cell lymphoma with hemolytic crisis developed twenty years after
      the onset of Evans syndrome.
AB  - A 65-year-old woman was diagnosed with Coombs-positive autoimmune hemolytic
      anemia (AIHA) and pure red cell aplasia (PRCA) in May 1992. One month later, her
      PRCA went into remission following treatment but she developed idiopathic
      thrombocytopenic purpura and was diagnosed with Evans syndrome. Although her
      condition resolved with administration of prednisolone and azathioprine, it was
      necessary to continue treatment with gradual tapering over the following two
      decades. In October 2012, her hemolytic anemia again worsened, and lymph node
      swelling, splenomegaly and B symptoms developed. She was diagnosed as having
      diffuse large B-cell lymphoma (DLBCL) based on lymph node biopsy. However, AIHA
      was not considered to be the cause of her hemolytic anemia, but rather to be
      related to DLBCL. This was because a Coombs test and other extensive
      investigations for Coombs negative-AIHA yielded negative results. The patient
      underwent CHOP therapy, and all of her symptoms improved. Herein, we report this
      rare case in which DLBCL developed after the onset of Evans syndrome.

PMID- 24881921
TI  - Posterior reversible encephalopathy syndrome following acute pancreatitis during
      chemotherapy for acute monocytic leukemia.
AB  - We describe an 18-year-old man with acute leukemia who presented with posterior
      reversible encephalopathy syndrome (PRES) shortly after developing acute
      pancreatitis. On day 15 after the third consolidation course with high-dose
      cytarabine, treatment with broad-spectrum antibiotics was initiated for febrile
      neutropenia. On day 16, he developed septic shock, and subsequently, acute
      respiratory distress syndrome (ARDS). After adding vancomycin, micafungin and
      high-dose methylprednisolone (mPSL) to his treatment regimen, these
      manifestations subsided. On day 22, he received hemodialysis for drug-induced
      acute renal failure. On day 24, he developed acute pancreatitis possibly due to
      mPSL; the following day he had generalized seizures, and was intubated.
      Cerebrospinal fluid findings were normal. Brain MRI revealed hyperintense signals
      on FLAIR images and increased apparent diffusion coefficient values in the sub
      cortical and deep white matter areas of the bilateral temporal and occipital
      lobes, indicative of vasogenic edema. Thus, we diagnosed PRES. Blood pressure,
      seizures and volume status were controlled, with MRI findings showing improvement
      by day 42. He was extubated on day 32 and discharged on day 49 without
      complications. Although little is known about PRES following acute pancreatitis,
      clinicians should be aware that this condition may develop.

PMID- 24881922
TI  - Acquired factor X deficiency developed four years after autologous
      transplantation in a patient with multiple myeloma associated with systemic AL
      amyloidosis.
AB  - We describe a case of acquired factor X deficiency after high-dose melphalan with
      autologous stem cell transplantation (HDM/ASCT) for multiple myeloma (MM) with
      systemic AL amyloidosis. A 68-year-old woman with renal amyloidosis was diagnosed
      as having MM in 2007. She achieved a partial response after VAD (vincristine,
      adriamycin, dexamethasone) therapy and HDM/ASCT. In December 2011, coagulation
      tests revealed a prolonged prothrombin time (PT) of 17.6 sec and she was
      administered vitamin K. In January 2012, she received low anterior resection with
      colostomy for rectal cancer. She received fresh frozen plasma (FFP) infusion but
      the perioperative bleeding tendency persisted. In February 2012, she was referred
      from surgery for colostomy closure. She showed no progression of MM and had
      prolonged PT, corrected by mixing with normal plasma. Factor X activity was
      markedly decreased. She was diagnosed as having an acquired factor X deficiency
      and was given FFP infusion for colostomy closure. Although acquired factor X
      deficiency after HDM/ASCT for MM with systemic AL amyloidosis is rare, we should
      be aware of the possibility of this disease in MM patients with a bleeding
      tendency.

PMID- 24881923
TI  - Clinical experience of bendamustine for adult Langerhans cell sarcoma.
AB  - A 40-year-old man was diagnosed with Langerhans cell histiocytosis (LCH) in
      October 2010. His LCH was refractory to conventional chemotherapy, and thus
      worsened to Langerhans cell sarcoma (LCS) in May 2011. Although we repeated
      combination chemotherapies, new infiltration of the liver and bone marrow, as
      well as primary lesions of the bone, lymph nodes, and skin, appeared. These
      intensive chemotherapies caused candida liver abscesses, invasive aspergillosis,
      disseminated varicella zoster virus infection and bacterial sepsis. We
      administered bendamustine for chemotherapy, which resulted in a partial response
      (PR) with no severe adverse events. Because of pancytopenia caused by secondary
      myelodysplastic syndrome, we stopped the bendamustine chemotherapy after two
      courses. PR was maintained for 4 months. We plan to perform allogeneic
      hematopoietic stem cell transplantation from a sibling donor after a conditioning
      regimen. Optimal therapy for adult LCH, which is a rare and treatment-resistant
      disease, has yet to be established. Bendamustine is a potential chemotherapeutic
      agent for standard treatment of LCS.

PMID- 24881924
TI  - Effective control of skin reaction by air sandwich technique in a patient with
      IgE-kappa myeloma treated with subcutaneous bortezomib injection.
AB  - A 53-year-old man initially presented with costalgia and was diagnosed with MM,
      based on the pathological findings. IgE monoclonal protein was detected by Serum
      protein electrophoresis (SPEP) and, surprisingly, IgE was elevated to 7,950,000
      IU/ml. Monitoring the disease response during treatment, we employed
      quantification of serum M protein at SPEP, because IgE levels were found to be
      inaccurate and erratic. The patient was treated with CyBorD. He found injection
      site reactions to be very burdensome, due to extreme skin changes. The diameter
      of the hyperpigmentation area was 8 cm. To reduce the severity of this reaction,
      we used an air sandwich technique, and succeeded in ameliorating the skin
      changes.

PMID- 24881927
TI  - Ovarian reserve in adult patients with childhood-onset lupus: a possible
      deleterious effect of methotrexate?
AB  - OBJECTIVES: To assess ovarian reserve markers and anti-corpus luteum antibodies
      (anti-CoL) in adult patients with childhood-onset systemic lupus erythematosus (c
      SLE). METHOD: Fifty-seven adult c-SLE female patients and 21 healthy controls
      were evaluated for anti-CoL. Ovarian reserve was assessed by: follicle
      stimulating hormone (FSH), luteinizing hormone (LH), oestradiol, anti-Mullerian
      hormone (AMH), and antral follicle count (AFC). Demographic data, menstrual
      abnormalities, disease activity, damage, and treatment were also analysed.
      RESULTS: The median current age was similar in adult c-SLE patients and controls
      (27.7 vs. 27.7 years, p = 0.414). The medians of AMH (1.1 vs. 1.5 ng/mL, p =
      0.037) and AFC (6 vs. 16, p < 0.001) were significantly reduced in SLE patients
      compared to controls without significant menstrual abnormalities. Anti-CoL were
      solely observed in c-SLE patients (16% vs. 0%, p = 0.103) and were not associated
      with demographic data, ovarian reserve parameters, disease activity/damage, and
      treatment. Further evaluation of c-SLE patients treated with cyclophosphamide
      revealed a higher median of FSH levels compared to c-SLE patients not treated
      with cyclophosphamide and controls (8.8 vs. 5.7 vs. 5.6 IU/L, p = 0.032) and
      lower median AMH (0.4 vs. 1.5 vs. 1.5 ng/mL, p = 0.004) and AFC (4.0 vs. 6.5 vs.
      16 IU/L, p = 0.001) levels. Nineteen patients treated exclusively with
      methotrexate demonstrated a negative correlation between the cumulative dose and
      AMH levels (p = 0.027, r = -0.507). CONCLUSIONS: The present study demonstrated
      for the first time that a high cumulative methotrexate dose is a possible cause
      of subclinical ovarian dysfunction in adult c-SLE patients. Further studies are
      required to confirm this deleterious effect in other rheumatic diseases,
      particularly juvenile idiopathic arthritis and idiopathic inflammatory myopathy.

PMID- 24881928
TI  - Clothing-related motorcycle injuries in Pakistan: findings from a surveillance
      study.
AB  - This study aims to assess the burden and patterns of clothing-related motorcycle
      injuries in Karachi, Pakistan. Data were extracted from an ongoing traffic injury
      surveillance system. In three years (2007-2009), out of 99155 road traffic injury
      cases there were 986 (0.9%) cases of clothing-related motorcycle injuries. Most
      cases were females (73.9%) and pillion riders (80.6%). The crashes involving
      clothing-related injuries were mostly single vehicle (98.5%), and largely
      resulted in injuries to the external body (60.3%), limbs (51.0%), head (41.5%)
      and face (35.9%). One-third of injuries were either moderate (26.7%) or severe
      (10.2%) while 10 (1.01%) deaths were reported. Female gender (11.4%), age >= 45
      years (19.4%), pillion riding (11.3%) and crashes occurring at intersections
      (12.3%) were more likely to result in moderate or severe injury as compared to
      other users (P < 0.001). Injuries due to entanglement of loose fitting clothing
      in motorcycles are not uncommon in Karachi. Awareness campaigns for prevention of
      such injuries may involve promotion of appropriate dressing for motorcycle riding
      including close wrapping of clothes and encouraging installations of covers on
      the rear wheels and drive chains.

PMID- 24881929
TI  - Crystalline anatase-rich titanium can reduce adherence of oral streptococci.
AB  - Dental implant abutments that emerge through the mucosa are rapidly covered with
      a salivary protein pellicle to which bacteria bind, initiating biofilm formation.
      In this study, adherence of early colonizing streptococci, Streptococcus
      gordonii, Streptococcus oralis, Streptococcus mitis and Streptococcus sanguinis
      to two saliva-coated anodically oxidized surfaces was compared with that on
      commercially pure titanium (CpTi). Near edge X-ray absorption (NEXAFS) showed
      crystalline anatase was more pronounced on the anodically oxidized surfaces than
      on the CpTi. As revealed by fluorescence microscopy, a four-species mixture, as
      well as individual bacterial species, exhibited lower adherence after 2 h to the
      saliva-coated, anatase-rich surfaces than to CpTi. Since wettability did not
      differ between the saliva-coated surfaces, differences in the concentration
      and/or configuration of salivary proteins on the anatase-rich surfaces may
      explain the reduced bacterial binding effect. Anatase-rich surfaces could thus
      contribute to reduced overall biofilm formation on dental implant abutments
      through diminished adherence of early colonizers.

PMID- 24881930
TI  - Bacterial pathogenesis: Bacteria choose to fight and flee.

PMID- 24881931
TI  - Pulmonary hypertension and emphysema: cure targeting a common cause?

PMID- 24881932
TI  - Extracorporeal membrane oxygenation for severe acute respiratory failure: yes we
      can! (But should we?).

PMID- 24881933
TI  - Sedative choice: a critical decision.

PMID- 24881934
TI  - Cross-coverage in the intensive care unit: more than meets the "i"?

PMID- 24881935
TI  - Sweet success should set tongues wagging. A portrait of airway muscle injury in
      sleep apnea.

PMID- 24881936
TI  - Resolution of pulmonary edema. Thirty years of progress.
AB  - In the last 30 years, we have learned much about the molecular, cellular, and
      physiological mechanisms that regulate the resolution of pulmonary edema in both
      the normal and the injured lung. Although the physiological mechanisms
      responsible for the formation of pulmonary edema were identified by 1980, the
      mechanisms that explain the resolution of pulmonary edema were not well
      understood at that time. However, in the 1980s several investigators provided
      novel evidence that the primary mechanism for removal of alveolar edema fluid
      depended on active ion transport across the alveolar epithelium. Sodium enters
      through apical channels, primarily the epithelial sodium channel, and is pumped
      into the lung interstitium by basolaterally located Na/K-ATPase, thus creating a
      local osmotic gradient to reabsorb the water fraction of the edema fluid from the
      airspaces of the lungs. The resolution of alveolar edema across the normally
      tight epithelial barrier can be up-regulated by cyclic adenosine monophosphate
      (cAMP)-dependent mechanisms through adrenergic or dopamine receptor stimulation,
      and by several cAMP-independent mechanisms, including glucocorticoids, thyroid
      hormone, dopamine, and growth factors. Whereas resolution of alveolar edema in
      cardiogenic pulmonary edema can be rapid, the rate of edema resolution in most
      patients with acute respiratory distress syndrome (ARDS) is markedly impaired, a
      finding that correlates with higher mortality. Several mechanisms impair the
      resolution of alveolar edema in ARDS, including cell injury from unfavorable
      ventilator strategies or pathogens, hypoxia, cytokines, and oxidative stress. In
      patients with severe ARDS, alveolar epithelial cell death is a major mechanism
      that prevents the resolution of lung edema. 

PMID- 24881938
TI  - Update in chronic obstructive pulmonary disease 2013.

PMID- 24881939
TI  - Update in sleep medicine 2013.

PMID- 24881941
TI  - Percutaneous transluminal pulmonary angioplasty for chronic thromboembolic
      pulmonary hypertension with severe right heart failure.

PMID- 24881940
TI  - Better off blue: BMPR-2 mutation, arteriovenous malformation, and pulmonary
      arterial hypertension.

PMID- 24881942
TI  - Abnormalities in airway epithelial junction formation in chronic obstructive
      pulmonary disease.

PMID- 24881943
TI  - Our enlightened understanding of the risks of persistent delirium.

PMID- 24881937
TI  - Asthma in Hispanics. An 8-year update.
AB  - This review provides an update on asthma in Hispanics, a diverse group tracing
      their ancestry to countries previously under Spanish rule. A marked variability
      in the prevalence and morbidity from asthma remains among Hispanic subgroups in
      the United States and Hispanic America. In the United States, Puerto Ricans and
      Mexican Americans have high and low burdens of asthma, respectively (the
      "Hispanic Paradox"). This wide divergence in asthma morbidity among Hispanic
      subgroups is multifactorial, likely reflecting the effects of known (secondhand
      tobacco smoke, air pollution, psychosocial stress, obesity, inadequate treatment)
      and potential (genetic variants, urbanization, vitamin D insufficiency, and
      eradication of parasitic infections) risk factors. Barriers to adequate asthma
      management in Hispanics include economic and educational disadvantages, lack of
      health insurance, and no access to or poor adherence with controller medications
      such as inhaled corticosteroids. Although considerable progress has been made in
      our understanding of asthma in Hispanic subgroups, many questions remain. Studies
      of asthma in Hispanic America should focus on environmental or lifestyle factors
      that are more relevant to asthma in this region (e.g., urbanization, air
      pollution, parasitism, and stress). In the United States, research studies should
      focus on risk factors that are known to or may diverge among Hispanic subgroups,
      including but not limited to epigenetic variation, prematurity, vitamin D level,
      diet, and stress. Clinical trials of culturally appropriate interventions that
      address multiple aspects of asthma management in Hispanic subgroups should be
      prioritized for funding. Ensuring high-quality healthcare for all remains a
      pillar of eliminating asthma disparities. 

PMID- 24881944
TI  - Only a small subset of sedation-related delirium is innocuous: we cannot let our
      guard down.

PMID- 24881945
TI  - Reply: Is the glass of delirium half full or half empty?

PMID- 24881946
TI  - Reply: The importance of determining the reason for intensive care unit delirium.

PMID- 24881947
TI  - Importance of the kidney, vessels, and heart with administration of beta2
      adrenergic receptor agonists in patients susceptible to acute respiratory
      distress syndrome.

PMID- 24881948
TI  - Reply: Importance of the kidney, vessels, and heart with administration of beta2
      adrenergic receptor agonists in patients susceptible to acute respiratory
      distress syndrome.

PMID- 24881949
TI  - Reply: beta2-agonists and acute respiratory distress syndrome.

PMID- 24881950
TI  - A giant clot.

PMID- 24881951
TI  - Spontaneous pneumomediastinum associated with pneumorachis.

PMID- 24881953
TI  - Learning sung lyrics aids retention in normal ageing and Alzheimer's disease.
AB  - Previous studies have suggested that presenting to-be-memorised lyrics in a
      singing mode, instead of a speaking mode, may facilitate learning and retention
      in normal adults. In this study, seven healthy older adults and eight
      participants with mild Alzheimer's disease (AD) learned and memorised lyrics that
      were either sung or spoken. We measured the percentage of words recalled from
      these lyrics immediately and after 10 minutes. Moreover, in AD participants, we
      tested the effect of successive learning episodes for one spoken and one sung
      excerpt, as well as long-term retention after a four week delay. Sung conditions
      did not influence lyrics recall in immediate recall but increased delayed recall
      for both groups. In AD, learning slopes for sung and spoken lyrics did not show a
      significant difference across successive learning episodes. However, sung lyrics
      showed a slight advantage over spoken ones after a four week delay. These results
      suggest that singing may increase the load of initial learning but improve long
      term retention of newly acquired verbal information. We further propose some
      recommendations on how to maximise these effects and make them relevant for
      therapeutic applications. 

PMID- 24881954
TI  - A zeta (zeta)-pipet tip to reduce the spontaneously induced electrical charge of
      a dispensed aqueous droplet.
AB  - We report that the zeta potential of a pipet tip's inner surface is one of the
      crucial parameters for controlling the electrical charge of the dispensed
      droplet. Since the charge is unexpected and undesirable for most experiments in
      various fields of science and, thereby, they can cause unsuspected problems,
      reducing the charge on a dispensed droplet is important for the results of
      pipetting-based experiments. We fabricate a graphene-based nanocomposite-coated
      pipet tip, which we called a zeta-pipet tip, as a proof-of-concept example to
      reduce the zeta potential of the pipet tip's inner surface. The fabricated zeta
      pipet tip can successfully mitigate the undesired droplet separation in the
      droplet merging experiments in an oil bath, which is one of the unexpected
      effects caused by the electrification. The findings of this study provide helpful
      guidelines for researchers in many fields of science and technology, who utilize
      a pipet tip in their respective experiments. 

PMID- 24881955
TI  - Concentration profiles of metals in breast milk, drinking water, and soil:
      relationship between matrices.
AB  - The concentrations of Cd, Cr, Cu, Hg, Mn, Ni, Pb, Sn, and Zn were determined in
      breast milk of women living in Conceicao das Alagoas, Minas Gerais, Brazil. The
      potential relationships between metal levels in samples of breast milk, drinking
      water, and soils collected in the study area were also established. Metal levels
      in breast milk, except Cr, were lower in comparison to WHO reference
      concentrations. Zinc was the predominant element in breast milk and drinking
      water samples, with a median level of 46.2 and 82.2 MUg . L(-1), respectively.
      Soils presented a different pattern of metal concentrations with respect to those
      found in breast milk and drinking water, Chromium showed the highest median
      levels (148 mg . kg(-1)), while a certain predominance of Zn and Cu was also
      observed (47.0 and 43.0 mg . kg(-1), respectively). Similar profiles were
      observed when comparing metal concentrations in drinking water and breast milk
      (chi-square chi(2) = 14.36; p < 0.05). In contrast, breast milk-soil and drinking
      water-soil metal concentration profiles showed significant differences (chi(2) =
      635.05 and chi(2) = 721.78, respectively; p < 0.05). These results indicate that
      drinking water is an important exposure pathway for metals to newborns through
      breast milk. Further studies should be aimed at assessing the body burdens of
      metals in that population and at evaluating the potential relationships in the
      concentrations in biological and environmental matrices as well as at estimating
      the contribution of dietary intake of metals. In addition, the presence of other
      chemical pollutants in breast milk should be also studied in order to assess the
      combined newborn exposure to other contaminants.

PMID- 24881956
TI  - Environmental and structural proteomics.

PMID- 24881957
TI  - Galanin-3 receptor antagonism by SNAP 37889 reduces motivation to self-administer
      alcohol and attenuates cue-induced reinstatement of alcohol-seeking in iP rats.
AB  - The neuropeptide galanin has a role in promoting alcohol consumption and general
      feeding behavior. The galanin-3 receptor (GALR3) subtype is implicated in
      modulating the consumption of alcohol and has therefore been identified as a
      potential target for new pharmacotherapies to treat alcohol use disorders. We
      have previously shown that the selective GALR3 antagonist SNAP 37889 reduced
      voluntary alcohol consumption in iP (alcohol-preferring) rats. The present study
      firstly aimed to investigate the effect of GALR3 antagonism on the motivational
      properties of alcohol. Secondly, the potential of GALR3 as a therapeutic target
      in the prevention of relapse was investigated in response to alcohol-conditioned
      cues. Administration of SNAP 37889 (30 mg/kg, i.p.) significantly reduced the
      breakpoint for ethanol under a progressive-ratio operant responding schedule of
      reinforcement. SNAP 37889 also significantly reduced reinstatement of alcohol
      seeking in response to re-exposure to conditioned cues that were previously
      associated with the availability of alcohol. Collectively, results from the
      current study provide new evidence of GALR3 involvement in cue-induced relapse
      and provide further evidence that GALR3 antagonism reduces the motivational drive
      to consume alcohol. These findings validate further research in to the potential
      use of SNAP 37889 and other GALR3 antagonists to treat alcohol abuse disorders in
      humans. 

PMID- 24881958
TI  - Ursolic acid induces apoptosis through mitochondrial intrinsic pathway and
      suppression of ERK1/2 MAPK in HeLa cells.
AB  - Ursolic acid (UA), a natural pentacyclic triterpenoid compound, has been
      demonstrated to induce apoptosis in various tumors. The aim of the present study
      was to elucidate the molecular mechanisms of UA-induced apoptosis in HeLa cells.
      Here, we reported that UA induced apoptosis through the mitochondrial intrinsic
      pathway in HeLa cells, as shown by release of cytosol cytochrome c, activation of
      caspase-9 and -3, reduction of Bcl-2 and Bcl-xL, and increase of Bax and Bak. UA
      down-regulated the phosphorylation of ERK1/2 and p38, whereas phosphorylation of
      JNK was unchanged. The roles of ERK1/2 and p38 were further confirmed using the
      ERK1/2 inhibitor (U0126) and p38 inhibitor (SB203580). U0126 markedly increased
      UA-induced the Bax/Bcl-2 ratio, the increase of cytosol cytochrome c, and the
      levels of cleaved caspase-3, but SB203580 had little effects on the above
      characters, suggesting the ERK1/2 signaling pathway is required for apoptosis.
      Furthermore, UA up-regulated DUSP 1, 2, 4, 5, 6, 7, 9, and 10 mRNA expressions,
      which may be a clue for the role of dephosphorylation of ERK1/2 and p38. These
      data suggested that the apoptotic mechanism of UA treatment in HeLa cells was
      through the mitochondrial intrinsic pathway and closely associated with the
      suppression of the ERK1/2 signaling pathway. 

PMID- 24881959
TI  - Dopaminergic hyperactivity accompanied by hyperlocomotion in C57BL/6J-bg(J)/bg(J)
      (beige-J) mice.
AB  - Genetic factors affect locomotor activity, which mainly depends on the activation
      of dopaminergic systems. C57BL/6J-bg(J)bg(J) (beige-J) mice, which exhibit
      deficiencies in immunological function, show behavioral hyperactivity. The
      present study was designed to investigate the locomotor activity of beige-J mice
      accompanied by a change in the dopaminergic system. Beige-J mice showed higher
      locomotor activity and dopamine turnover, whereas splenectomy reduced this
      hyperlocomotion and dopamine turnover. These results suggest that beige-J mice
      could be suitable as an experimental animal model for investigating
      hyperactivation of the dopaminergic system, and the spleen may contribute to the
      susceptibility of dopaminergic systems to activation. 

PMID- 24881960
TI  - Antiallodynic action of 1-(3-(9H-Carbazol-9-yl)-1-propyl)-4-(2-methyoxyphenyl)-4
      piperidinol (NNC05-2090), a betaine/GABA transporter inhibitor.
AB  - The GABAergic system in the spinal cord has been shown to participate in
      neuropathic pain in various animal models. GABA transporters (GATs) play a role
      in controlling the synaptic clearance of GABA; however, their role in neuropathic
      pain remains unclear. In the present study, we compared the betaine/GABA
      transporter (BGT-1) with other GAT subtypes to determine its participation in
      neuropathic pain using a mouse model of sciatic nerve ligation. 1-(3-(9H-Carbazol
      9-yl)-1-propyl)-4-(2-methyoxyphenyl)-4-piperidinol (NNC05-2090), an inhibitor
      that displays moderate selectivity for BGT-1, had an antiallodynic action on
      model mice treated through both intrathecally and intravenous administration
      routes. On the other hand, SKF89976A, a selective GAT-1 inhibitor, had a weak
      antiallodynic action, and (S)-SNAP5114, an inhibitor that displays selectivity
      for GAT-3, had no antiallodynic action. Systemic analysis of these compounds on
      GABA uptake in CHO cells stably expressing BGT-1 revealed that NNC05-2090 not
      only inhibited BGT-1, but also serotonin, noradrenaline, and dopamine
      transporters, using a substrate uptake assay in CHO cells stably expressing each
      transporter, with IC50: 5.29, 7.91, and 4.08 MUM, respectively. These values were
      similar to the IC50 value at BGT-1 (10.6 MUM). These results suggest that the
      antiallodynic action of NNC05-2090 is due to the inhibition of both BGT-1 and
      monoamine transporters. 

PMID- 24881961
TI  - CSML2SBML: a novel tool for converting quantitative biological pathway models
      from CSML into SBML.
AB  - CSML and SBML are XML-based model definition standards which are developed with
      the aim of creating exchange formats for modeling, visualizing and simulating
      biological pathways. In this article we report a release of a format convertor
      for quantitative pathway models, namely CSML2SBML. It translates models encoded
      by CSML into SBML without loss of structural and kinetic information. The
      simulation and parameter estimation of the resulting SBML model can be carried
      out with compliant tool CellDesigner for further analysis. The convertor is based
      on the standards CSML version 3.0 and SBML Level 2 Version 4. In our experiments,
      11 out of 15 pathway models in CSML model repository and 228 models in Macrophage
      Pathway Knowledgebase (MACPAK) are successfully converted to SBML models. The
      consistency of the resulting model is validated by libSBML Consistency Check of
      CellDesigner. Furthermore, the converted SBML model assigned with the kinetic
      parameters translated from CSML model can reproduce the same dynamics with
      CellDesigner as CSML one running on Cell Illustrator. CSML2SBML, along with its
      instructions and examples for use are available at http://csml2sbml.csml.org. 

PMID- 24881962
TI  - Molecular typing of Legionella pneumophila serogroup 1 clinical strains isolated
      in Italy.
AB  - Molecular typing methods for discriminating different bacterial isolates are
      essential epidemiological tools in prevention and control of Legionella
      infections and outbreaks. A selection of 56 out of 184 Legionella pneumophila
      serogroup 1 (Lp1) clinical isolates, collected from different Italian regions
      between 1987 and 2012, and stored at the National Reference Laboratory for
      Legionella, were typed by monoclonal antibody (MAb) subgrouping, amplified
      fragment length polymorphism (AFLP) and sequence based typing (SBT). These
      strains were isolated from 39 community (69.6%), 14 nosocomial (25%) and 3 travel
      associated (5.4%) Legionnaires'disease cases. MAb typing results showed a
      prevalence of MAb 3/1 positive isolates (75%) with the Philadelphia subgroup
      representing 35.7%, followed by Knoxville (23.2%), Benidorm (12.5%),
      Allentown/France (1.8%), Allentown/France-Philadelphia (1.8%). The remaining 25%
      were MAb 3/1 negative, namely 11 Olda (19.6%), 2 Oxford (3.6%) and 1 Bellingham
      (1.8%) subgroups. AFLP analysis detected 20 different genomic profiles. SBT
      analysis revealed 32 different sequence types (STs) with high diversity of STs
      (IODSTs=0.952) 12 of which were never described before. ST1 and ST23 were most
      frequently isolated as observed worldwide. A helpful analysis of data from SBT,
      MAb subgrouping and AFLP is provided, as well as a comparison to the Lp1 types
      investigated from other countries. This study describes the first Italian Lp1
      strains database, providing molecular epidemiology data useful for future
      epidemiological investigations, especially of travel associated Legionnaires'
      diseases (TALD) cases, Italy being the country associated with the highest number
      of clusters. 

PMID- 24881963
TI  - The role of Staphylococcus epidermidis in neonatal sepsis: guarding angel or
      pathogenic devil?
AB  - Neonatal late-onset sepsis (LOS) is a serious problem in neonatal intensive care.
      Coagulase-negative staphylococci, especially Staphylococcus epidermidis, have
      emerged as the predominant pathogen of LOS in very low birth weight (VLBW)
      infants, accounting for up to 77.9% of neonatal LOS in industrialized countries
      and 46.5% in some developing regions. VLBW neonates with indwelling medical
      devices are most susceptible for S. epidermidis sepsis, the incidence rate of
      which is approximately 25%. However, S. epidermidis primarily plays a commensal
      role on human host and is of evolutionary importance to newborns, by inhibiting
      virulent pathogens and educating the innate immune system. Recent advances in
      molecular microbiology show that S. epidermidis is a bacterial species equipped
      with remarkable genetic flexibility, and can employ a multitude of mechanisms to
      become adapted to the changing environment. Extrinsic factors in the neonatal
      ward, such as the interruption of skin barrier by medical devices and the
      selective pressure due to antibiotics, contribute to the conversion of S.
      epidermidis from a member of the skin microflora to an infectious agent.
      Furthermore, neonates are predisposed for S. epidermidis infections due to their
      distinct immunological characteristics. A better understanding of the dichotomy
      of S. epidermidis and the underlying mechanisms may inspire new anti-infectious
      strategies. 

PMID- 24881964
TI  - [Survey on the management of acute renal failure and renal replacement techniques
      in Spanish intensive care units].
AB  - AIM: To analyze knowledge and experience in the diagnosis and management of acute
      renal failure (ARF) and the use of renal replacement therapy (RRT) in different
      Spanish Intensive Care Units (ICUs). DESIGN: A case series with a survey
      conducted by the Nephro-Intensive Care Working Group of the SEMICYUC was compiled
      between January and November 2011. SCOPE: Spanish national ICUs. INTERVENTIONS: A
      survey of 28 questions with multiple and open responses. PARTICIPANTS: The survey
      was sent to 99 ICUs. Volunteers consisting of the medical staff belonging to the
      51 ICUs that responded. Main variables of interest General characteristics of
      hospitals and ICUs, definitions of ARF and RRT (indications and management).
      RESULTS: RIFLE/AKIN scales to define ARF (47%). ARF diagnosis: plasma creatinine
      (80.4%), creatinine clearance (52.9%). Protocols for RRT: 72.5%. RRT in non-renal
      indications: 70.6%. Indications for initiation of RRT: oliguria, increased
      creatinine and urea. End of RRT: increased diuresis. RRT dose: 21-35 ml/kg/h
      (41.2%), 36-45ml/kg/h (33.3%). CONCLUSIONS: There is great variability in the ARF
      detection methods, and adequate incorporation of the RIFLE/AKIN systems to daily
      clinical practice in the ICU is still lacking. Written protocols aimed at
      establishing an early diagnosis of ARF are needed, based on these systems. On the
      other hand, there is growing interest in RRT, despite the fact that there are no
      definitive indications or guidelines on the use and handling of such techniques.

PMID- 24881965
TI  - [Movements after brain death].

PMID- 24881966
TI  - Preimplantation genetic diagnosis for carriers with chromosomal translocations
      undergoing assisted reproductive technologies therapy.

PMID- 24881968
TI  - Gonads and gametes as indicators of speciation, arthropod phylogeny and taxonomic
      understanding.

PMID- 24881967
TI  - Insulin protects against Abeta-induced spatial memory impairment, hippocampal
      apoptosis and MAPKs signaling disruption.
AB  - Alzheimer disease (AD) is a progressive neurodegenerative disease characterized
      by extracellular deposits of beta amyloid (Abeta) and neuronal loss particularly
      in the hippocampus. Accumulating evidences have implied that insulin signaling
      impairment plays a key role in the pathology of AD; as much as it is considered
      as type 3 Diabetes. MAPKs are a group of signaling molecules which are involved
      in pathobiology of AD. Therefore this study was designed to investigate if
      intrahippocampal insulin hinders Abeta-related memory deterioration, hippocampal
      apoptosis and MAPKs signaling alteration induced by Abeta. Adult male Sprague
      Dawely rats weighing 250-300 g were used in this study. The canules were
      implanted bilaterally into CA1 region. Abeta25-35 was administered during first 4
      days after surgery (5 MUg/2.5 MUL/daily). Insulin treatment (0.5 or 6 mU) was
      done during days 4-9. The animal's learning and memory capability was assessed on
      days 10-13 using Morris water maze. After finishing of behavioral studies the
      hippocampi was isolated and the amount of hippocampal cleaved caspase 3 (the
      landmark of apoptosis) and the phosphorylated (activated) forms of P38, JNK and
      ERK was analyzed by western blot. The results showed that insulin in 6 but not
      0.5 mU reversed the memory loss induced by Abeta25-35. Western blot analysis
      revealed that Abeta25-35 induced elevation of caspase-3 and all 3 MAPks subfamily
      activity, while insulin in 6 mu restored ERK and P38 activation but has no effect
      on JNK. This study disclosed that intrahippocampal insulin treatment averts not
      only Abeta-induced memory deterioration but also hippocampal caspase-3, ERK and
      P38 activation. 

PMID- 24881969
TI  - Nutrition management guideline for maple syrup urine disease: an evidence- and
      consensus-based approach.
AB  - In an effort to increase harmonization of care and enable outcome studies, the
      Genetic Metabolic Dietitians International (GMDI) and the Southeast Regional
      Newborn Screening and Genetics Collaborative (SERC) are partnering to develop
      nutrition management guidelines for inherited metabolic disorders (IMD) using a
      model combining both evidence- and consensus-based methodology. The first
      guideline to be completed is for maple syrup urine disease (MSUD). This report
      describes the methodology used in its development: formulation of five research
      questions; review, critical appraisal and abstraction of peer-reviewed studies
      and unpublished practice literature; and expert input through Delphi surveys and
      a nominal group process. This report includes the summary statements for each
      research question and the nutrition management recommendations they generated.
      Each recommendation is followed by a standardized rating based on the strength of
      the evidence and consensus used. The application of technology to build the
      infrastructure for this project allowed transparency during development of this
      guideline and will be a foundation for future guidelines. Online open access of
      the full, published guideline allows utilization by health care providers,
      researchers, and collaborators who advise, advocate and care for individuals with
      MSUD and their families. There will be future updates as warranted by
      developments in research and clinical practice. 

PMID- 24881970
TI  - Investigating neurological deficits in carriers and affected patients with
      ornithine transcarbamylase deficiency.
AB  - BACKGROUND: Urea cycle disorders are caused by dysfunction in any of the six
      enzymes and two transport proteins involved in urea biosynthesis. Our study
      focuses on ornithine transcarbamylase deficiency (OTCD), an X-linked disorder
      that results in a dysfunctional mitochondrial enzyme, which prevents the
      synthesis of citrulline from carbamoyl phosphate and ornithine. This enzyme
      deficiency can lead to hyperammonemic episodes and severe cerebral edema. The
      objective of this study was to use a cognitive battery to expose the cognitive
      deficits in asymptomatic carriers of OTCD. MATERIALS AND METHODS: In total, 81
      participants were recruited as part of a larger urea cycle disorder imaging
      consortium study. There were 25 symptomatic participants (18 female, 7 male, 25.6
      year s +/- 12.72 years), 20 asymptomatic participants (20 female, 0 male, 37.6
      years +/- 15.19 years), and 36 healthy control participants (21 female, 15 male,
      29.8 years +/- 13.39 years). All participants gave informed consent to
      participate and were then given neurocognitive batteries with standard scores and
      T scores recorded. RESULTS: When stratified by symptomatic participant,
      asymptomatic carrier, and control, the results showed significant differences in
      measures of executive function (e.g. CTMT and Stroop) and motor ability (Purdue
      Assembly) between all groups tested. Simple attention, academic measures,
      language and non-verbal motor abilities showed no significant differences between
      asymptomatic carriers and control participants, however, there were significant
      differences between symptomatic and control participant performance in these
      measures. CONCLUSIONS: In our study, asymptomatic carriers of OTCD showed no
      significant differences in cognitive function compared to control participants
      until they were cognitively challenged with fine motor tasks, measures of
      executive function, and measures of cognitive flexibility. This suggests that
      cognitive dysfunction is best measurable in asymptomatic carriers after they are
      cognitively challenged.

PMID- 24881971
TI  - Availability of a baseline Electrocardiogram changes the application of the
      Sclarovsky-Birnbaum Myocardial Ischemia Grade.
AB  - BACKGROUND AND AIMS: The electrocardiogram (ECG) based Sclarovsky-Birnbaum
      Ischemia Grade may be used to determine the prognosis of patients with ST
      elevation myocardial infarction (STEMI). However, application of the method is
      based on assumption of the baseline QRS morphology. Thus, the aims of this study
      were to determine if the baseline QRS morphology was correctly assumed based on
      an ECG recorded during induced ischemia, and if reference to the baseline ECG
      altered the designated Ischemia Grade. METHODS: Sixty-three patients with chronic
      ischemic heart disease that underwent elective percutaneous transluminal coronary
      angioplasty were included. Baseline ECG and ECG during the procedure were
      recorded. In the latter, Ischemia Grade was classified according to assumed
      baseline QRS morphology. Then the baseline ECG was used as reference and Ischemia
      Grade was determined based on change from the baseline ECG. RESULTS: In 66.6%
      (42/63) of patients the criteria for STEMI were fulfilled; the incidence was
      similar between left anterior descending (LAD) and right coronary artery (RCA)
      occlusion. In LAD patients who fulfilled STEMI criteria, assumption of baseline
      QRS morphology in involved leads was accurate in only 35% (7/20) and this altered
      the Ischemia Grade in 10% (2/20) of patients. In RCA patients who fulfilled STEMI
      criteria, assumption of baseline QRS morphology in involved leads was accurate in
      77.3% (17/22) and this altered the Ischemia Grade in 9.1% (2/22) of patients.
      CONCLUSION: Application of the Sclarovsky-Birnbaum Ischemia Grade with reference
      to a baseline ECG altered Ischemia Grade in approximately 10% of patients. All
      patients that were reclassified were assigned a higher Ischemia Grade. Future
      research is needed to determine the impact of availability of the baseline ECG on
      the clinical diagnostic and prognostic performances of the Sclarovsky-Birnbaum
      Ischemia Grade.

PMID- 24881972
TI  - The STAFF III ECG database and its significance for methodological development
      and evaluation.
AB  - The development of new techniques for detection and characterization of transient
      myocardial ischemia has benefited considerably from the STAFF III database,
      acquired in patients receiving elective prolonged percutaneous transluminal
      coronary angiography. The present article reviews a range of techniques developed
      and/or evaluated on the ECG signals of this database, including techniques for
      exploring abnormal intra-QRS potentials, QRS slopes, QRS angles, T wave
      morphology, T wave alternans, spatiotemporal ECG information, as well as heart
      rate dynamics. The detection of changes in body position is also briefly reviewed
      as it is intimately related to ischemia detection. 

PMID- 24881973
TI  - Hypertension: an urgent need for global control and prevention.

PMID- 24881974
TI  - Syrian health crisis in Lebanon.

PMID- 24881975
TI  - Polio eradication: the CIA and their unintended victims.

PMID- 24881976
TI  - The dilemma of vaginal breech delivery worldwide.

PMID- 24881977
TI  - Nebivolol and valsartan: useful treatment for hypertension?

PMID- 24881978
TI  - Focus on blood pressure as a major risk factor.

PMID- 24881979
TI  - The drugs do work: blood pressure improvement in England.

PMID- 24881982
TI  - E-cigarette regulations in Italy: fluctuating and confusing.

PMID- 24881981
TI  - Marshall Lightowlers: tackling parasitic diseases.

PMID- 24881983
TI  - Time to reconsider thyroid cancer screening in Fukushima.

PMID- 24881984
TI  - The war on cancer: time for a new terminology.

PMID- 24881985
TI  - Renal denervation for resistant hypertension--the Symplicity HTN-1 study.

PMID- 24881986
TI  - Renal denervation for resistant hypertension-the Symplicity HTN-1 study.

PMID- 24881987
TI  - Renal denervation for resistant hypertension-the Symplicity HTN-1 study -
      Authors' reply.

PMID- 24881988
TI  - Renal denervation for resistant hypertension-the Symplicity HTN-1 study.

PMID- 24881989
TI  - Interpretation of optical coherence tomography images.

PMID- 24881990
TI  - Interpretation of optical coherence tomography images.

PMID- 24881991
TI  - Interpretation of optical coherence tomography images.

PMID- 24881992
TI  - Interpretation of optical coherence tomography images - Authors' reply.

PMID- 24881995
TI  - Hypertension management in England: a serial cross-sectional study from 1994 to
      2011.
AB  - BACKGROUND: Hypertension is the leading risk factor contributing to the global
      burden of disease. We aimed to assess the change in blood pressure management
      between 1994 and 2011 in England with a series of annual surveys. METHODS: We did
      a serial cross-sectional study of five Health Survey for England surveys based on
      nationally representative samples of non-institutionalised adults (aged >=16
      years). Mean blood pressure levels and rates of awareness, treatment, and control
      of hypertension were assessed. Hypertension was defined as systolic blood
      pressure 140 mm Hg or higher, diastolic blood pressure 90 mm Hg or higher, or
      receiving treatment for high blood pressure. FINDINGS: The mean blood pressure
      levels of men and women in the general population and among patients with treated
      hypertension progressively improved between 1994 and 2011. In patients with
      treated hypertension, blood pressure improved from 150.0 (SE 0.59)/80.2 (0.27) mm
      Hg to 135.4 (0.58)/73.5 (0.41) mm Hg. Awareness, treatment, and control rates
      among men and women combined also improved significantly across each stage of
      this 17-year period, with the prevalence of control among treated patients almost
      doubling from 33% (SE 1.4) in 1994 to 63% (1.7) in 2011. Nevertheless, of all
      adults with survey-defined hypertension in 2011, hypertension was controlled in
      only 37%. INTERPRETATION: If the same systematic improvement in all aspects of
      hypertension management continues until 2022, 80% of patients with treated
      hypertension will have controlled blood pressure levels with a potential annual
      saving of about 50,000 major cardiovascular events. FUNDING: None.

PMID- 24881994
TI  - Blood pressure and incidence of twelve cardiovascular diseases: lifetime risks,
      healthy life-years lost, and age-specific associations in 1.25 million people.
AB  - BACKGROUND: The associations of blood pressure with the different manifestations
      of incident cardiovascular disease in a contemporary population have not been
      compared. In this study, we aimed to analyse the associations of blood pressure
      with 12 different presentations of cardiovascular disease. METHODS: We used
      linked electronic health records from 1997 to 2010 in the CALIBER (CArdiovascular
      research using LInked Bespoke studies and Electronic health Records) programme to
      assemble a cohort of 1.25 million patients, 30 years of age or older and
      initially free from cardiovascular disease, a fifth of whom received blood
      pressure-lowering treatments. We studied the heterogeneity in the age-specific
      associations of clinically measured blood pressure with 12 acute and chronic
      cardiovascular diseases, and estimated the lifetime risks (up to 95 years of age)
      and cardiovascular disease-free life-years lost adjusted for other risk factors
      at index ages 30, 60, and 80 years. This study is registered at
      ClinicalTrials.gov, number NCT01164371. FINDINGS: During 5.2 years median follow
      up, we recorded 83,098 initial cardiovascular disease presentations. In each age
      group, the lowest risk for cardiovascular disease was in people with systolic
      blood pressure of 90-114 mm Hg and diastolic blood pressure of 60-74 mm Hg, with
      no evidence of a J-shaped increased risk at lower blood pressures. The effect of
      high blood pressure varied by cardiovascular disease endpoint, from strongly
      positive to no effect. Associations with high systolic blood pressure were
      strongest for intracerebral haemorrhage (hazard ratio 1.44 [95% CI 1.32-1.58]),
      subarachnoid haemorrhage (1.43 [1.25-1.63]), and stable angina (1.41 [1.36
      1.46]), and weakest for abdominal aortic aneurysm (1.08 [1.00-1.17]). Compared
      with diastolic blood pressure, raised systolic blood pressure had a greater
      effect on angina, myocardial infarction, and peripheral arterial disease, whereas
      raised diastolic blood pressure had a greater effect on abdominal aortic aneurysm
      than did raised systolic pressure. Pulse pressure associations were inverse for
      abdominal aortic aneurysm (HR per 10 mm Hg 0.91 [95% CI 0.86-0.98]) and strongest
      for peripheral arterial disease (1.23 [1.20-1.27]). People with hypertension
      (blood pressure >=140/90 mm Hg or those receiving blood pressure-lowering drugs)
      had a lifetime risk of overall cardiovascular disease at 30 years of age of 63.3%
      (95% CI 62.9-63.8) compared with 46.1% (45.5-46.8) for those with normal blood
      pressure, and developed cardiovascular disease 5.0 years earlier (95% CI 4.8
      5.2). Stable and unstable angina accounted for most (43%) of the cardiovascular
      disease-free years of life lost associated with hypertension from index age 30
      years, whereas heart failure and stable angina accounted for the largest
      proportion (19% each) of years of life lost from index age 80 years.
      INTERPRETATION: The widely held assumptions that blood pressure has strong
      associations with the occurrence of all cardiovascular diseases across a wide age
      range, and that diastolic and systolic associations are concordant, are not
      supported by the findings of this high-resolution study. Despite modern
      treatments, the lifetime burden of hypertension is substantial. These findings
      emphasise the need for new blood pressure-lowering strategies, and will help to
      inform the design of randomised trials to assess them. FUNDING: Medical Research
      Council, National Institute for Health Research, and Wellcome Trust.

PMID- 24881996
TI  - The scoliosis of Richard III, last Plantagenet King of England: diagnosis and
      clinical significance.

PMID- 24881997
TI  - Iron/iron oxide core/shell nanoparticles for magnetic targeting MRI and near
      infrared photothermal therapy.
AB  - The development of photothermal agents (PTAs) with good stability, low toxicity,
      highly targeting ability and photothermal conversion efficiency is an essential
      pre-requisite to near-infrared photothermal therapy (PTT) in vivo. Herein, we
      report the readily available PEGylated Fe@Fe3O4 NPs, which possess triple
      functional properties in one entity - targeting, PTT, and imaging. Compared to Au
      nanorods, they exhibit comparable photothermal conversion efficiency (~20%), and
      much higher photothermal stability. They also show a high magnetization value and
      transverse relaxivity (~156 mm(-1) s(-1)), which should be applied for magnetic
      targeting MRI. With the Nd-Fe-B magnet (0.5 T) beside the tumour for 12 h on the
      xenograft HeLa tumour model, PEGylated Fe@Fe3O4 NPs exhibit an obvious
      accumulation. In tumour, the intensity of MRI signal is ~ three folds and the
      increased temperature is ~ two times than those without magnetic targeting,
      indicating the good magnetic targeting ability. Notably, the intrinsic high
      photothermal conversion efficiency and selective magnetic targeting effect of the
      NPs in tumour play synergistically in highly efficient ablation of cancer cells
      in vitro and in vivo. 

PMID- 24881999
TI  - Continuous stimulation of the plant immune system by the peptide elicitor PIP-1
      is required for phytoalexin biosynthesis in tobacco cells.
AB  - The peptide elicitor PIP-1 (YGIHTH-nh2) induced various defense responses in
      tobacco cells. Types of defense responses induced by PIP-1 were different based
      on its concentration range: oxidative burst (an early response) was induced at
      low micromolar levels, but phytoalexin production (a late response) required
      about 10-50-fold higher concentrations than those required for oxidative burst.
      We assumed that rapid decreases in the PIP-1 concentration due to enzymatic
      hydrolysis in the culture media could cause this difference. To examine the
      potential impact of such degradation particularly on induction of phytoalexin
      biosynthesis, we designed a degradation-resistant analogue, MePIP-1, in which the
      amide bond between the fifth and sixth residues was N-methylated. MePIP-1 was
      considerably more stable than PIP-1 and induced significant phytoalexin
      production upon treatment at low micromolar levels. Further investigation of the
      mechanism of action of MePIP-1 showed a requirement of continuous elicitor
      stimulation for 3-6 h for the phytoalexin production, which is likely to be
      regulated by long-lasting MAP kinase activation. 

PMID- 24881998
TI  - Reprogramming of mouse somatic cells into pluripotent stem-like cells using a
      combination of small molecules.
AB  - Somatic cells can be reprogrammed to generate induced pluripotent stem cells
      (iPSCs) by overexpression of four transcription factors, Oct4, Klf4, Sox2, and c
      Myc. However, exogenous expression of pluripotency factors raised concerns for
      clinical applications. Here, we show that iPS-like cells (iPSLCs) were generated
      from mouse somatic cells in two steps with small molecule compounds. In the first
      step, stable intermediate cells were generated from mouse astrocytes by Bmi1.
      These cells called induced epiblast stem cell (EpiSC)-like cells (iEpiSCLCs) are
      similar to EpiSCs in terms of expression of specific markers, epigenetic state,
      and ability to differentiate into three germ layers. In the second step,
      treatment with MEK/ERK and GSK3 pathway inhibitors in the presence of leukemia
      inhibitory factor resulted in conversion of iEpiSCLCs into iPSLCs that were
      similar to mESCs, suggesting that Bmi1 is sufficient to reprogram astrocytes to
      partially reprogrammed pluripotency. Next, Bmi1 function was replaced with Shh
      activators (oxysterol and purmorphamine), which demonstrating that combinations
      of small molecules can compensate for reprogramming factors and are sufficient to
      directly reprogram mouse somatic cells into iPSLCs. The chemically induced
      pluripotent stem cell-like cells (ciPSLCs) showed similar gene expression
      profiles, epigenetic status, and differentiation potentials to mESCs. 

PMID- 24882000
TI  - A role for stargazin in experience-dependent plasticity.
AB  - During development, neurons are constantly refining their connections in response
      to changes in activity. Experience-dependent plasticity is a key form of synaptic
      plasticity, involving changes in alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid receptor (AMPAR) accumulation at synapses. Here, we
      report a critical role for the AMPAR auxiliary subunit stargazin in this
      plasticity. We show that stargazin is functional at the retinogeniculate synapse
      and that in the absence of stargazin, the refinement of the retinogeniculate
      synapse is specifically disrupted during the experience-dependent phase.
      Importantly, we found that stargazin expression and phosphorylation increased
      with visual deprivation and led to reduced AMPAR rectification at the
      retinogeniculate synapse. To test whether stargazin plays a role in homeostatic
      plasticity, we turned to cultured neurons and found that stargazin
      phosphorylation is essential for synaptic scaling. Overall, our data reveal an
      important role for stargazin in regulating AMPAR abundance and composition at
      glutamatergic synapses during homeostatic and experience-dependent plasticity. 

PMID- 24882001
TI  - Use of host-like peptide motifs in viral proteins is a prevalent strategy in host
      virus interactions.
AB  - Viruses interact extensively with host proteins, but the mechanisms controlling
      these interactions are not well understood. We present a comprehensive analysis
      of eukaryotic linear motifs (ELMs) in 2,208 viral genomes and reveal that viruses
      exploit molecular mimicry of host-like ELMs to possibly assist in host-virus
      interactions. Using a statistical genomics approach, we identify a large number
      of potentially functional ELMs and observe that the occurrence of ELMs is often
      evolutionarily conserved but not uniform across virus families. Some viral
      proteins contain multiple types of ELMs, in striking similarity to complex
      regulatory modules in host proteins, suggesting that ELMs may act combinatorially
      to assist viral replication. Furthermore, a simple evolutionary model suggests
      that the inherent structural simplicity of ELMs often enables them to tolerate
      mutations and evolve quickly. Our findings suggest that ELMs may allow fast
      rewiring of host-virus interactions, which likely assists rapid viral evolution
      and adaptation to diverse environments. 

PMID- 24882002
TI  - Dppa5 improves hematopoietic stem cell activity by reducing endoplasmic reticulum
      stress.
AB  - Developmental pluripotency-associated 5 (Dppa5) is an RNA binding protein highly
      expressed in undifferentiated pluripotent stem cells. Here, we demonstrate that
      Dppa5 is a regulator of hematopoietic stem cells (HSCs) that critically governs
      reconstitution capacity after bone marrow transplantation. Ectopic expression of
      Dppa5 followed by in vitro culture robustly increased HSC reconstitution levels
      through suppression of endoplasmic reticulum (ER) stress and apoptosis.
      Remarkably, a chemical chaperone that decreases ER stress in HSCs also increases
      HSC engraftment. Conversely, knockdown of Dppa5 impaired the long-term
      reconstitution ability of HSCs due to elevated ER stress levels, suggesting that
      ER stress regulation is physiologically important for proper HSC function in
      vivo. Thus, Dppa5 represents a pivotal connection between ER stress regulation
      and stem cell properties in HSCs. The findings also demonstrate that protein
      quality control is critical for the maintenance, survival, and function of HSCs
      in vivo and ex vivo. 

PMID- 24882003
TI  - Signatures of conformational stability and oxidation resistance in proteomes of
      pathogenic bacteria.
AB  - Protein oxidation is known to compromise vital cellular functions. Therefore,
      invading pathogenic bacteria must resist damage inflicted by host defenses via
      reactive oxygen species. Using comparative genomics and experimental approaches,
      we provide multiple lines of evidence that proteins from pathogenic bacteria have
      acquired resistance to oxidative stress by an increased conformational stability.
      Representative pathogens exhibited higher survival upon HSP90 inhibition and a
      less-oxidation-prone proteome. A proteome signature of the 46 pathogenic bacteria
      encompasses 14 physicochemical features related to increasing protein
      conformational stability. By purifying ten representative proteins, we
      demonstrate in vitro that proteins with a pathogen-like signature are more
      resistant to oxidative stress as a consequence of their increased conformational
      stability. A compositional signature of the pathogens' proteomes allowed the
      design of protein fragments more resilient to both unfolding and carbonylation,
      validating the relationship between conformational stability and oxidability with
      implications for synthetic biology and antimicrobial strategies. 

PMID- 24881993
TI  - Efficacy and safety of nebivolol and valsartan as fixed-dose combination in
      hypertension: a randomised, multicentre study.
AB  - BACKGROUND: The fixed-dose combination of any two antihypertensive drugs from
      different drug classes is typically more effective in reducing blood pressure
      than a dose increase of component monotherapy. We assessed the efficacy and
      safety of a fixed-dose combination of a vasodilating beta blocker (nebivolol) and
      an angiotensin II receptor blocker (valsartan) in adults with hypertension.
      METHODS: We did an 8-week, phase 3, multicentre, randomised, double-blind,
      placebo-controlled, parallel-group trial at 401 US sites. Participants (age >=18
      years) with hypertension but with blood pressure less than 180/110 mm Hg were
      randomly assigned (2:2:2:2:2:2:2:1) by a 24-h interactive web response system in
      blocks of 15 to 4 weeks of double-blind treatment with nebivolol and valsartan
      fixed-dose combination (5 and 80 mg/day, 5 and 160 mg/day, or 10 and 160 mg/day),
      nebivolol (5 mg/day or 20 mg/day), valsartan (80 mg/day or 160 mg/day), or
      placebo. Doses were doubled in weeks 5-8; results are reported according to the
      final dose. Participants and research staff were masked to treatment allocation.
      The primary and key secondary endpoints were changes from baseline to week 8 in
      diastolic and systolic blood pressure, respectively. The primary statistical
      comparison was between the highest fixed-dose combination dose and the highest
      monotherapy doses; lower doses were then compared if this comparison was positive
      (Hochberg method for multiple testing). Efficacy analyses were by intention to
      treat. Safety assessments included monitoring of adverse events. Continuous
      efficacy parameters were analysed using an ANCOVA model; binary outcomes were
      analysed using a logistic regression model. This study is registered with
      ClinicalTrials.gov, NCT01508026. FINDINGS: Between Jan 6, 2012, and March 15,
      2013, 4161 patients were randomly assigned (277 to placebo and 554-555 to each
      active comparator group), 4118 of whom were included in the primary analysis. At
      week 8, the fixed-dose combination 20 and 320 mg/day group had significantly
      greater reductions in diastolic blood pressure from baseline than both nebivolol
      40 mg/day (least-squares mean difference -1.2 mm Hg, 95% CI -2.3 to -0.1;
      p=0.030) and valsartan 320 mg/day (-4.4 mm Hg, -5.4 to -3.3; p<0.0001); all other
      comparisons were also significant, favouring the fixed-dose combinations (all
      p<0.0001). All systolic blood pressure comparisons were also significant (all
      p<0.01). At least one treatment-emergent adverse event was experienced by 30-36%
      of participants in each group. INTERPRETATION: Nebivolol and valsartan fixed-dose
      combination is an effective and well-tolerated treatment option for patients with
      hypertension. FUNDING: Forest Research Institute.

PMID- 24882004
TI  - High-definition reconstruction of clonal composition in cancer.
AB  - The extensive genetic heterogeneity of cancers can greatly affect therapy success
      due to the existence of subclonal mutations conferring resistance. However, the
      characterization of subclones in mixed-cell populations is computationally
      challenging due to the short length of sequence reads that are generated by
      current sequencing technologies. Here, we report cloneHD, a probabilistic
      algorithm for the performance of subclone reconstruction from data generated by
      high-throughput DNA sequencing: read depth, B-allele counts at germline
      heterozygous loci, and somatic mutation counts. The algorithm can exploit the
      added information present in correlated longitudinal or multiregion samples and
      takes into account correlations along genomes caused by events such as copy
      number changes. We apply cloneHD to two case studies: a breast cancer sample and
      time-resolved samples of chronic lymphocytic leukemia, where we demonstrate that
      monitoring the response of a patient to therapy regimens is feasible. Our work
      provides new opportunities for tracking cancer development. 

PMID- 24882006
TI  - Transient accumulation of 5-carboxylcytosine indicates involvement of active
      demethylation in lineage specification of neural stem cells.
AB  - 5-Methylcytosine (5mC) is an epigenetic modification involved in regulation of
      gene activity during differentiation. Tet dioxygenases oxidize 5mC to 5
      hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine
      (5caC). Both 5fC and 5caC can be excised from DNA by thymine-DNA glycosylase
      (TDG) followed by regeneration of unmodified cytosine via the base excision
      repair pathway. Despite evidence that this mechanism is operative in embryonic
      stem cells, the role of TDG-dependent demethylation in differentiation and
      development is currently unclear. Here, we demonstrate that widespread oxidation
      of 5hmC to 5caC occurs in postimplantation mouse embryos. We show that 5fC and
      5caC are transiently accumulated during lineage specification of neural stem
      cells (NSCs) in culture and in vivo. Moreover, 5caC is enriched at the cell-type
      specific promoters during differentiation of NSCs, and TDG knockdown leads to
      increased 5fC/5caC levels in differentiating NSCs. Our data suggest that active
      demethylation contributes to epigenetic reprogramming determining lineage
      specification in embryonic brain. 

PMID- 24882005
TI  - Intertissue control of the nucleolus via a myokine-dependent longevity pathway.
AB  - Recent evidence indicates that skeletal muscle influences systemic aging, but
      little is known about the signaling pathways and muscle-released cytokines
      (myokines) responsible for this intertissue communication. Here, we show that
      muscle-specific overexpression of the transcription factor Mnt decreases age
      related climbing defects and extends lifespan in Drosophila. Mnt overexpression
      in muscle autonomously decreases the expression of nucleolar components and
      systemically decreases rRNA levels and the size of the nucleolus in adipocytes.
      This nonautonomous control of the nucleolus, a regulator of ribosome biogenesis
      and lifespan, relies on Myoglianin, a myokine induced by Mnt and orthologous to
      human GDF11 and Myostatin. Myoglianin overexpression in muscle extends lifespan
      and decreases nucleolar size in adipocytes by activating p38 mitogen-activated
      protein kinase (MAPK), whereas Myoglianin RNAi in muscle has converse effects.
      Altogether, these findings highlight a key role for myokine signaling in the
      integration of signaling events in muscle and distant tissues during aging. 

PMID- 24882007
TI  - Break-induced replication is a source of mutation clusters underlying kataegis.
AB  - Clusters of simultaneous multiple mutations can be a source of rapid change
      during carcinogenesis and evolution. Such mutation clusters have been recently
      shown to originate from DNA damage within long single-stranded DNA (ssDNA) formed
      at resected double-strand breaks and dysfunctional replication forks. Here, we
      identify double-strand break (DSB)-induced replication (BIR) as another powerful
      source of mutation clusters that formed in nearly half of wild-type yeast cells
      undergoing BIR in the presence of alkylating damage. Clustered mutations were
      primarily formed along the track of DNA synthesis and were frequently associated
      with additional breakage and rearrangements. Moreover, the base specificity,
      strand coordination, and strand bias of the mutation spectrum were consistent
      with mutations arising from damage in persistent ssDNA stretches within
      unconventional replication intermediates. Altogether, these features closely
      resemble kataegic events in cancers, suggesting that replication intermediates
      during BIR may be the most prominent source of mutation clusters across species. 

PMID- 24882008
TI  - NK cell receptor NKp46 regulates graft-versus-host disease.
AB  - Hematopoietic stem cell transplantation (HSCT) is often the only curative
      treatment for a wide variety of hematologic malignancies. Donor selection in
      these diseases is crucial, given that transplanted cells can mediate not only the
      desired graft-versus-leukemia effect but also graft-versus-host disease (GVHD).
      Here, we demonstrate that in the absence of NKp46, a major killer receptor
      expressed by human and mouse natural killer (NK) cells, GVHD is greatly
      exacerbated, resulting in rapid mortality of the transplanted animals because of
      infection with commensal bacteria. Furthermore, we demonstrate that the
      exacerbated GVHD is the result of an altered ability of immune cells to respond
      to stimulation by immature dendritic cells. Because high and low expression of
      NKp46 on NK cells is observed in different individuals, our data indicate that
      choosing NKp46-high donors for the treatment of different hematologic
      malignancies might lead to better tumor eradication while minimizing GVHD.

PMID- 24882009
TI  - IKKalpha promotes intestinal tumorigenesis by limiting recruitment of M1-like
      polarized myeloid cells.
AB  - The recruitment of immune cells into solid tumors is an essential prerequisite of
      tumor development. Depending on the prevailing polarization profile of these
      infiltrating leucocytes, tumorigenesis is either promoted or blocked. Here, we
      identify IkappaB kinase alpha (IKKalpha) as a central regulator of a tumoricidal
      microenvironment during intestinal carcinogenesis. Mice deficient in IKKalpha
      kinase activity are largely protected from intestinal tumor development that is
      dependent on the enhanced recruitment of interferon gamma (IFNgamma)-expressing
      M1-like myeloid cells. In IKKalpha mutant mice, M1-like polarization is not
      controlled in a cell-autonomous manner but, rather, depends on the interplay of
      both IKKalpha mutant tumor epithelia and immune cells. Because therapies aiming
      at the tumor microenvironment rather than directly at the mutated cancer cell may
      circumvent resistance development, we suggest IKKalpha as a promising target for
      colorectal cancer (CRC) therapy.

PMID- 24882010
TI  - XIAP restricts TNF- and RIP3-dependent cell death and inflammasome activation.
AB  - X-linked inhibitor of apoptosis protein (XIAP) has been identified as a potent
      regulator of innate immune responses, and loss-of-function mutations in XIAP
      cause the development of the X-linked lymphoproliferative syndrome type 2 (XLP-2)
      in humans. Using gene-targeted mice, we show that loss of XIAP or deletion of its
      RING domain lead to excessive cell death and IL-1beta secretion from dendritic
      cells triggered by diverse Toll-like receptor stimuli. Aberrant IL-1beta
      secretion is TNF dependent and requires RIP3 but is independent of cIAP1/cIAP2.
      The observed cell death also requires TNF and RIP3 but proceeds independently of
      caspase-1/caspase-11 or caspase-8 function. Loss of XIAP results in aberrantly
      elevated ubiquitylation of RIP1 outside of TNFR complex I. Virally infected Xiap(
      /-) mice present with symptoms reminiscent of XLP-2. Our data show that XIAP
      controls RIP3-dependent cell death and IL-1beta secretion in response to TNF,
      which might contribute to hyperinflammation in patients with XLP-2.

PMID- 24882011
TI  - Dysregulation of the miR-324-5p-CUEDC2 axis leads to macrophage dysfunction and
      is associated with colon cancer.
AB  - CUEDC2, a CUE-domain-containing protein, modulates inflammation, but its
      involvement in tumorigenesis is still poorly understood. Here, we report that
      CUEDC2 is a key regulator of macrophage function and critical for protection
      against colitis-associated tumorigenesis. CUEDC2 expression is dramatically
      upregulated during macrophage differentiation, and CUEDC2 deficiency results in
      excessive production of proinflammatory cytokines. The level of CUEDC2 in
      macrophages is modulated by miR- 324-5p. We find that Cuedc2 KO mice are more
      susceptible to dextran-sodium-sulfate-induced colitis, and macrophage
      transplantation results suggest that the increased susceptibility results from
      the dysfunction of macrophages lacking CUEDC2. Furthermore, we find that Cuedc2
      KO mice are more prone to colitis-associated cancer. Importantly, CUEDC2
      expression is almost undetectable in macrophages in human colon cancer, and this
      decreased CUEDC2 expression is associated with high levels of interleukin-4 and
      miR-324-5p. Thus, CUEDC2 plays a crucial role in modulating macrophage function
      and is associated with both colitis and colon tumorigenesis.

PMID- 24882012
TI  - Widespread changes in the posttranscriptional landscape at the Drosophila oocyte
      to-embryo transition.
AB  - The oocyte-to-embryo transition marks the onset of development. The initial phase
      of this profound change from the differentiated oocyte to the totipotent embryo
      occurs in the absence of both transcription and mRNA degradation. Here we combine
      global polysome profiling, ribosome-footprint profiling, and quantitative mass
      spectrometry in a comprehensive approach to delineate the translational and
      proteomic changes that occur during this important transition in Drosophila. Our
      results show that PNG kinase is a critical regulator of the extensive changes in
      the translatome, acting uniquely at this developmental window. Analysis of the
      proteome in png mutants provided insights into the contributions of translation
      to changes in protein levels, revealing a compensatory dynamic between
      translation and protein turnover during proteome remodeling at the return to
      totipotency. The proteome changes additionally suggested regulators of meiosis
      and early embryogenesis, including the conserved H3K4 demethylase LID, which we
      demonstrated is required during this period despite transcriptional inactivity. 

PMID- 24882013
TI  - A presynaptic role for the cytomatrix protein GIT in synaptic vesicle recycling.
AB  - Neurotransmission involves the exo-endocytic cycling of synaptic vesicles (SVs)
      within nerve terminals. Exocytosis is facilitated by a cytomatrix assembled at
      the active zone (AZ). The precise spatial and functional relationship between
      exocytic fusion of SVs at AZ membranes and endocytic SV retrieval is unknown.
      Here, we identify the scaffold G protein coupled receptor kinase 2 interacting
      (GIT) protein as a component of the AZ-associated cytomatrix and as a regulator
      of SV endocytosis. GIT1 and its D. melanogaster ortholog, dGIT, are shown to
      directly associate with the endocytic adaptor stonin 2/stoned B. In Drosophila
      dgit mutants, stoned B and synaptotagmin levels are reduced and stoned B is
      partially mislocalized. Moreover, dgit mutants show morphological and functional
      defects in SV recycling. These data establish a presynaptic role for GIT in SV
      recycling and suggest a connection between the AZ cytomatrix and the endocytic
      machinery. 

PMID- 24882015
TI  - Low bioavailability steroids in inflammatory bowel disease: an old chestnut or a
      whole new ballgame?
AB  - At present, therapy of inflammatory bowel disease is still far from being fully
      satisfactory; old drugs like steroids, for instance, still represent a
      cornerstone in the treatment of active disease despite their associated important
      side effects and incomplete clinical efficacy. In the last years, new therapeutic
      strategies have been suggested in order to avoid or at least limit steroids use
      and in this direction the so-called low bioavailability steroids appeared to be a
      promising therapeutic weapon; however, some grey areas about their real utility
      and manner of use still remain. The aim of this review is to evaluate the
      available evidence about the use of oral budesonide and beclomethasone
      dipropionate in inflammatory bowel disease, to critically assess their current
      position in the therapeutic algorithm of these diseases and to give simple and
      practical indications for their use in every-day clinical practice. 

PMID- 24882016
TI  - Identification and characterization of a goose-type lysozyme from sewage snail
      Physa acuta.
AB  - Freshwater snail Physa acuta has been considered as an important invasive species
      and medical mollusc. Field investigation has shown that this snail could survive
      better than other snails in polluted water bodies. To understand the immune
      mechanisms of P. acuta, suppression subtractive hybridization hepatopancreas cDNA
      library has been constructed with bacterial challenge. In this study, a full
      length cDNA of a novel goose-type lysozyme (PALysG) has been identified from P.
      acuta by EST and RACE technique. The conservative structure domains share high
      homology with other molluscan g-type lysozymes including the SLT domain, the
      substrate binding sites, the catalytic residues, three alpha-helices structures
      and six molluscan specific cysteines. Meanwhile, PALysG is the first record of
      goose-type lysozyme in Gastropoda. Real-time PCR indicated that PALysG mRNA had
      been expressed significantly at high levels in hepatopancreas for 8-48 h. PALysG
      recombinant protein displayed the lytic activity of g-type lysozyme with other
      organisms against Micrococcus lysodikicus.

PMID- 24882014
TI  - Do static and dynamic insulin resistance indices perform similarly in predicting
      pre-diabetes and type 2 diabetes?
AB  - AIMS: We designed a study to compare the predictive power of static and dynamic
      insulin resistance indices for categorized pre-diabetes (PDM)/type 2 diabetes
      (DM). METHODS: Participants included 1134 adults aged 18-60 years old with normal
      glucose at baseline who completed both baseline and 6-years later follow-up
      surveys. Insulin resistance indices from baseline data were used to predict risk
      of PDM or DM at follow-up. Two static indices and two dynamic indices were
      calculated from oral glucose tolerance test results (OGTT) at baseline. Area
      under the receiver operating characteristic curve (AROC) analysis was used to
      estimate the predictive ability of candidate indices to predict PDM/DM. A general
      estimation equation (GEE) model was applied to assess the magnitude of
      association of each index at baseline with the risk of PDM/DM at follow-up.
      RESULTS: The dynamic indices displayed the largest and statistically predictive
      AROC for PDM/DM diagnosed either by fasting glucose or by postprandial glucose.
      The bottom quartiles of the dynamic indices were associated with an elevated risk
      of PDM/DM vs. the top three quartiles. However, the static indices only performed
      significantly to PDM/DM diagnosed by fasting glucose. CONCLUSIONS: Dynamic
      insulin resistance indices are stronger predictors of future PDM/DM than static
      indices. This may be because dynamic indices better reflect the full range of
      physiologic disturbances in PDM/DM.

PMID- 24882018
TI  - Site-related differences in gene expression and bacterial densities in the mussel
      Bathymodiolus azoricus from the Menez Gwen and Lucky Strike deep-sea hydrothermal
      vent sites.
AB  - The deep-sea hydrothermal vent mussel Bathymodiolus azoricus is a symbiont
      bearing bivalve that is found in great abundance at the Menez Gwen and Lucky
      Strike hydrothermal vent sites and in close vicinity of the Azores region near
      the Mid-Atlantic Ridge (MAR). The physiological relationships that vent mussels
      have developed with their physical and chemical environments are likely to
      influence global gene expression profiles providing thus the means to investigate
      distinct biological markers predicting the origin of Bathymodiolus sp.
      irrespectively of their geographical localization. Differences found at gene
      expression levels, and between fluorescence in situ hybridization (FISH) and 16S
      rRNA amplicon sequencing results provided experimental evidence for the
      distinction of both Menez Gwen and Lucky Strike vent mussel individuals based on
      bacterial and vent mussel gene expression signatures and on the constitutive
      distribution and relative abundance of endosymbiotic bacteria within gill
      tissues. Our results confirmed the presence of methanotroph endosymbionts in
      Menez Gwen vent mussels whereas Lucky Strike specimens seem to harbor a different
      bacterial morphotype when a methane monooxygenase gene specific probe was used.
      No qualitative differences could be visualized between Menez Gwen and Lucky
      Strike individuals when tested with a sulfur-oxidizing-related probe.
      Quantitative PCR (qPCR) studies revealed different gene expression profiles in
      both Menez Gwen and Lucky Strike mussel gill tissues for the immune genes
      selected. Genes encoding transcription factors presented noticeably low levels of
      fold expression whether in Menez Gwen or Lucky Strike animals whereas the genes
      encoding effector molecules appeared to have higher levels expression in gill
      tissues from Menez Gwen animals. The peptidoglycan recognition molecule encoding
      gene, PGRP, presented the highest level of transcriptional activity among the
      genes analyzed in Menez Gwen mussel gill tissues, seconded by carcinolectin and
      thus denoting the relevance of immune recognition molecules in early stage of the
      immune responses onset. Genes regarded as encoding molecules involved in
      signaling pathways were consistently expressed in both Menez Gwen and Lucky
      Strike mussel gill tissues. Remarkably, the immunity-related GTPase encoding gene
      demonstrated, in Lucky Strike samples, the highest level of expression among the
      signaling molecule encoding genes tested when expressions levels were compared
      between Menez Gwen and Lucky Strike animals. A differential expression analysis
      of bacterial genes between Menez Gwen and Lucky Strike mussels indicated a clear
      expression signature in the latter animal gill tissues. The bacterial community
      structure ensued from the 16S rRNA sequencing analyses pointed at an unpredicted
      conservation of endosymbiont bacterial loads between Menez Gwen and Lucky Strike
      samples. Taken together, our results support the hypothesis that B. azoricus
      exhibits different transcriptional statuses while living in distinct hydrothermal
      vent sites may result in distinct gene expressions because of physico-chemical
      and/or symbiont densities differences.

PMID- 24882017
TI  - Transcriptional changes in Manila clam (Ruditapes philippinarum) in response to
      Brown Ring Disease.
AB  - Brown Ring Disease (BRD) is a bacterial infection affecting the economically
      important clam Ruditapes philippinarum. The disease is caused by a bacterium,
      Vibrio tapetis, that colonizes the edge of the mantle, altering the
      biomineralization process and normal shell growth. Altered organic shell matrices
      accumulate on the inner face of the shell leading to the formation of the typical
      brown ring in the extrapallial space (between the mantle and the shell). Even
      though structural and functional changes have been described in solid (mantle)
      and fluid (hemolymph and extrapallial fluids) tissues from infected clams, the
      underlying molecular alterations and responses remain largely unknown. This study
      was designed to gather information on clam molecular responses to the disease and
      to compare focal responses at the site of the infection (mantle and extrapallial
      fluid) with systemic (hemolymph) responses. To do so, we designed and produced a
      Manila clam expression oligoarray (15K Agilent) using transcriptomic data
      available in public databases and used this platform to comparatively assess
      transcriptomic changes in mantle, hemolymph and extrapallial fluid of infected
      clams. Results showed significant regulation in diseased clams of molecules
      involved in pathogen recognition (e.g. lectins, C1q domain-containing proteins)
      and killing (defensin), apoptosis regulation (death-associated protein, bcl-2)
      and in biomineralization (shell matrix proteins, perlucin, galaxin, chitin- and
      calcium-binding proteins). While most changes in response to the disease were
      tissue-specific, systemic alterations included co-regulation in all 3 tested
      tissues of molecules involved in microbe recognition and killing (complement
      related factors, defensin). These results provide a first glance at molecular
      alterations and responses caused by BRD and identify targets for future
      functional investigations. 

PMID- 24882019
TI  - Immune responses to live and inactivated Nocardia seriolae and protective effect
      of recombinant interferon gamma (rIFN gamma) against nocardiosis in ginbuna
      crucian carp, Carassius auratus langsdorfii.
AB  - Looking into the fact that substantial mortality and morbidity is associated with
      intracellular Gram +ve bacterium, Nocardia seriolae infection, an effective
      vaccine against this pathogen is necessary to control the significant losses in
      aquaculture practices. Therefore, an attempt was made to evaluate the effect of
      live (sub-lethal) and inactivated (antigenic form) N. seriolae on cellular and
      humoral immunity in ginbuna crucian carp, Carassius auratus langsdorfii as well
      as the therapeutic potency of recombinant interferon gamma (rIFN gamma) against
      N. seriolae infection. Effect of live and inactivated N. seriolae immunisation on
      the proliferation of CD4(+) T cells, CD8alpha(+) T cells and surface Ig M(+)
      cells in peripheral blood leucocytes, spleen, head kidney and trunk kidney of
      ginbuna was studied after 1st, 3rd, 7th, 15th and 30th day post immunisation. The
      percentage of CD8alpha(+) T cells in spleen and head kidney of ginbuna was
      significantly higher at 3rd day post immunisation. Similarly, surface Ig M(+)
      cells level was found to increase in both live and inactivated N. seriolae
      immunised groups. On the contrary, high percentage of CD4(+) T cells was observed
      in live N. seriolae immunised group in both the head and trunk kidneys at 30th
      day post immunisation. The humoral immune response to live and inactivated N.
      seriolae immunised ginbuna showed high antibody titre at 15th day post
      immunisation but the level declined subsequently in both the immunised groups. On
      challenge with virulent N. seriolae (1.2 * 10(8) CFU/ml), the relative percent
      survival was 62.5 and 75 in live and inactivated N. seriolae immunised groups,
      respectively. Furthermore, we have also studied the therapeutic potency of rIFN
      gamma and found the possible involvement of IFN gamma in resistance mechanism in
      fish. Administration of rIFN gamma into ginbuna (at 10 MUg/fish) one day before
      challenge study was found to protect ginbuna. The relative percent survival of
      ginbuna was 43.75 and 60 when challenged with 2 different doses of N. seriolae
      i.e., 1.2 * 10(8) CFU/ml and 5 * 10(7) CFU/ml, respectively. In summary, this
      study indicates that both forms of N. seriolae immunisation as well as rIFN gamma
      indeed elicit an effective protective immunity which will help in designing
      suitable vaccine and/or adjunct therapy against N. seriolae infection in fish. 

PMID- 24882021
TI  - Calculation of acoustical radiation force on microsphere by spherically-focused
      source.
AB  - Based on the ray acoustics approach, the trapping effects on a microsphere by an
      ideally spherically-focused ultrasound are discussed. The acoustical radiation
      force from a focused ultrasound beam on a spherical particle in a three
      dimensional sound field is calculated considering the effect of the attenuation
      of the ultrasound beam both inside the particle and in the surrounding medium.
      The results show that as long as the particle is in the range of the ultrasound
      beam and as long as the appropriate parameters of the transducer are selected,
      the particle will be captured in the vicinity of the focus of the ultrasound
      beam. Also, the particle radius and different parameters of the transducer are
      analyzed for their affect on the radiation force. 

PMID- 24882020
TI  - Torsional ultrasonic transducer computational design optimization.
AB  - A torsional piezoelectric ultrasonic sensor design is proposed in this paper and
      computationally tested and optimized to measure shear stiffness properties of
      soft tissue. These are correlated with a number of pathologies like tumors,
      hepatic lesions and others. The reason is that, whereas compressibility is
      predominantly governed by the fluid phase of the tissue, the shear stiffness is
      dependent on the stroma micro-architecture, which is directly affected by those
      pathologies. However, diagnostic tools to quantify them are currently not well
      developed. The first contribution is a new typology of design adapted to
      quasifluids. A second contribution is the procedure for design optimization, for
      which an analytical estimate of the Robust Probability Of Detection, called RPOD,
      is presented for use as optimality criteria. The RPOD is formulated
      probabilistically to maximize the probability of detecting the least possible
      pathology while minimizing the effect of noise. The resulting optimal transducer
      has a resonance frequency of 28 kHz.

PMID- 24882022
TI  - Under the looking glass.

PMID- 24882023
TI  - Feasibility and clinical utility of the Japanese version of the Abbey pain scale
      in Japanese aged care.
AB  - Active usage of observational pain scales in Japanese aged-care facilities has
      not been previously described. Therefore, to examine the feasibility and clinical
      utility of the Abbey Pain Scale-Japanese version (APS-J), this study examined the
      interrater reliability of the APS-J among a researcher, nurses, and care workers
      in aged-care facilities in Japan. This study also aimed to obtain nurses' and
      care workers' opinions on use of the scale. The following data were collected
      from 88 residents of two aged-care facilities: demographics, Barthel Index,
      Folstein Mini-Mental Examination (MMSE), 15-item Geriatric Depression Scale (GDS
      15), and APS-J for pain. The researchers, nurses, and care workers independently
      assessed the residents' pain by using the APS-J, and intraclass correlation
      coefficients (ICC) for interrater reliability and Cronbach alpha for internal
      consistency were examined. The ICC between researchers and nurses, researchers
      and care workers, and nurses and care workers were 0.68, 0.74, and 0.76,
      respectively. Nurses and care workers were invited for focus group interviews to
      obtain their opinions regarding APS-J use. During these interviews, nurses and
      care workers stated that the observational points of APS-J subscales were the
      criteria they normally used to evaluate residents' pain. Several nurses and care
      workers reported a gap between the estimated pain intensity and APS-J score.
      Unclear APS-J criteria, difficulties in observing residents, and insufficient
      practice guidelines were also reported. Our findings indicate that the APS-J has
      moderate reliability and clinically utility. To facilitate APS-J usage, education
      and clinical guidelines for pain management may be required for nurses and care
      workers. 

PMID- 24882024
TI  - Nonmedical methods to relieve low back pain caused by lumbar disc herniation: a
      descriptive study in northeastern Turkey.
AB  - Low back pain due to the effects of lumbar disc herniation is a common complaint
      of patients who often subsequently seek help from medical professionals. It is
      also a significant health problem which is quite difficult to treat. This
      descriptive study was conducted to determine nonmedical methods used by patients
      with lumbar disc herniation to relieve low back pain; the patients' intensity of
      low back pain when they were admitted to the hospital was also explored. Ninety
      two patients with lumbar disc herniation participated in this study, which was
      carried out at a university hospital in northeastern Turkey. Data were collected
      using a patient information form and the visual analog scale (VAS). When the
      patients were admitted to hospital, their mean VAS score was 6.56 +/- 2.45. The
      study results showed that as a first choice nearly all of the patients (94.6%)
      with lumbar disc herniation preferred consulting with their physicians before to
      obtain relief for low back pain. However, in addition to seeing their physician,
      more than one-half of these patients (57.6%) also used nonmedical methods. The
      primary nonmedical methods were hot/cold compresses, wrapping various substances
      on the back, and herbal preparations. An increase in pain was noted by 17.0% of
      patients after using nonmedical methods. Findings indicated that more than two
      thirds of patients experienced either no change or an increase in pain after
      using nonmedical methods to find relief. 

PMID- 24882025
TI  - Foot massage: effectiveness on postoperative pain in breast surgery patients.
AB  - The aim of this study was to determine the effect of foot massage on pain after
      breast surgery, and provide guidance for nurses in nonpharmacologic interventions
      for pain relief. This was a quasiexperimental study with a total of 70 patients
      who had undergone breast surgery (35 in the experimental group and 35 in the
      control group). Patients in the control group received only analgesic treatment,
      whereas those in the experimental group received foot massage in addition to
      analgesic treatment. Patients received the first dose of analgesics during
      surgery. As soon as patients came from the operating room, they were evaluated
      for pain severity. Patients whose pain severity scored >=4 according to the Short
      Form McGill Pain Questionnaire were accepted into the study. In the experimental
      group, pain and vital signs (arterial blood pressure, pulse, and respiration)
      were evaluated before foot massage at the time patients complained about pain
      (time 0) and then 5, 30, 60, 90, and 120 minutes after foot massage. In the
      control group, pain and vital signs were also evaluated when the patients
      complained about pain (time 0) and again at 5, 30, 60, 90, and 120 minutes, in
      sync with the times when foot massage was completed in the experimental group. A
      patient information form was used to collect descriptive characteristics data of
      the patients, and the Short-Form McGill Pain Questionnaire was used to determine
      pain severity. Data were analyzed for frequencies, mean, standard deviation, chi
      square, Student t, Pillai trace, and Bonferroni test. The results of the
      statistical analyses showed that patients in the experimental group experienced
      significantly less pain (p <= .001). Especially notable, patients in the
      experimental group showed a decrease in all vital signs 5 minutes after foot
      massage, but patients in the control group showed increases in vital signs except
      for heart rate at 5 minutes. The data obtained showed that foot massage in breast
      surgery patients was effective in postoperative pain management. 

PMID- 24882027
TI  - Integrating the concept of pain interference into pain management.
AB  - Undertreatment of pain is a significant problem. Nursing pain assessments have
      been identified as an area for improvement. This concept analysis sought to
      examine the use of pain interference as a measurement to assist pain management
      practices. Existing literature including the term pain interference was reviewed
      for the years 2000-2010. Pain interference is a common outcome measurement in
      clinical research. It is not well differentiated from other pain concepts in
      routine nursing pain assessments, nor consistently defined in research articles.
      Pain interference has been linked to quality of pain management and recommended
      as a standard of pain measurement. It aligns with current and emerging theories
      in pain and symptom control. Further exploration is needed to determine whether
      integrating this concept into nursing practice will result in improved patient
      pain experiences. 

PMID- 24882026
TI  - Older adults' pain communication during ambulatory medical visits: an exploration
      of communication accommodation theory.
AB  - The purpose of this descriptive secondary analysis was to explore the use of
      Communication Accommodation Theory as a framework to examine pain communication
      strategies used by older adults and their primary care practitioners during
      medical ambulatory care visits. Ambulatory medical visits for 22 older adults
      with moderate or greater osteoarthritis pain were audiotaped, transcribed
      verbatim, and coded by two independent raters for six a priori communication
      strategies derived from the attuning strategies of Communication Accommodation
      Theory: (1) patient selecting the pain topic; (2) patient taking a turn; (3)
      patient maintaining focus on the pain topic; (4) practitioner using an open-ended
      question without social desirability to start the pain discussion; (5)
      practitioner encouraging the patient to take a turn by asking open-ended
      questions; and (6) practitioner interruptions. The majority of practitioners did
      not start the pain discussion with an open-ended question, but did not interrupt
      the older adults as they discussed their pain. Five (22.7%) of the older adults
      did not discuss their osteoarthritis pain during the ambulatory medical visit.
      The majority of patients took their turn during the pain discussion, but did not
      maintain focus while describing important osteoarthritis pain information to
      their practitioner. Practitioners might assist older adults to communicate more
      information about their pain by initiating the pain discussion with an open-ended
      pain question. Older adults might provide more pain information to their
      practitioner by staying on the pain topic until they have completed all of the
      pain information they wish to discuss with the practitioner.

PMID- 24882028
TI  - Behavioral and physiologic indicators of pain in nonverbal patients with a
      traumatic brain injury: an integrative review.
AB  - The use of behavioral and physiologic indicators is recommended for pain
      assessment in nonverbal patients. Traumatic brain injuries (TBI) can lead to
      neurologic changes and affect the way patients respond to pain. As such, commonly
      used indicators of pain may not apply to TBI patients. This study aimed to review
      the literature about behavioral/physiologic indicators of pain in nonverbal TBI
      patients. An integrative review method was used. Medline (from 1948 to June
      2011), Cinahl, and Cochrane databases were searched using any combination of the
      terms brain injury, behavioral indicators, behavioral scale, physiologic
      indicators, pain, pain assessment, and pain measurement. All articles reporting
      expert opinion or original data about the validity of behavioral and/or
      physiologic indicators of pain in TBI patients were considered. For each article
      included, the quality of findings/clinical recommendations was graded
      independently by two raters using SORT taxonomy. Eight papers were reviewed.
      Overall, TBI patients seemed to present a wider range of behavioral reactions to
      pain than other adult populations. In addition to the commonly observed grimace,
      agitation, and increased muscle tension, 14%-72% of TBI patients showed raising
      eyebrows, opening eyes, weeping eyes, and absence of muscle tension when exposed
      to pain. Those atypical reactions appeared to be present only in the acute phase
      of TBIs recovery. Similarly to other populations, vital signs were identified as
      potential indicators of pain in TBI patients. Further research studying TBI
      patients and considering changes in level of consciousness, location/severity of
      brain injury, and administration of analgesic/sedative is needed. Until then,
      nurses should follow the current clinical recommendations. 

PMID- 24882029
TI  - Innovating in pain assessment of the critically ill: exploring cerebral near
      infrared spectroscopy as a bedside approach.
AB  - Nurses play a crucial role in the evaluation and treatment of pain in the
      critically ill patient. This responsibility is all the more critical with this
      particular population because many may not be able to self-report their pain
      level and the typical behavioral signs of pain may be subtle or absent. According
      to recent recommendations, vital signs should not be used as primary indicators
      of pain but rather considered as a cue to begin further assessment. Other than
      vital signs, human brain reactivity to pain has been extensively studied with the
      use mainly of magnetic resonance imaging and positron-emission tomography.
      However, the use of these sophisticated methods may be unrealistic in the
      critically ill. Of interest to assessing these patients in a clinical setting is
      the noninvasive measurement of regional cerebral tissue oxygenation with the near
      infrared spectroscopy (NIRS) technique. There are indications that NIRS is
      capable of detecting the cerebral hemodynamic changes associated with sensory
      stimuli, including pain. The objective of this review paper is to provide nurses
      with a better understanding of NIRS technology, including a review of the
      literature on functional studies that have used NIRS in critically ill
      populations, and how it could be used in both research and practice. Current NIRS
      techniques have well recognized limitations which must be considered carefully
      during the measurement and interpretation of signals. Thus, its clinical use is
      yet to be fully established. Nonetheless, cerebral NIRS technique as an approach
      to assess brain activity in response to pain should not be abandoned. 

PMID- 24882030
TI  - Neural and psychosocial mechanisms of pain sensitivity in fibromyalgia.
AB  - Fibromyalgia is a chronic musculoskeletal pain disorder that affects an estimated
      5 million adults in the U.S. The hallmark is burning, searing, tingling,
      shooting, stabbing, deep aching, or sharp pain. Fibromyalgia is generally
      considered to be a "central sensitivity syndrome" where central sensitization is
      regarded as the cause of pain in its own right. Nonetheless, the case continues
      to be made that all central and spatially distributed peripheral components of
      fibromyalgia pain would fade if the peripheral generators could be silenced.
      Although neural mechanisms are clearly important in pain sensitivity, cognitive
      and social mechanisms also need to be considered. The aim of this review is to
      examine four mechanisms responsible for heightened pain sensitivity in
      fibromyalgia: peripheral sensitization, central sensitization, cognitive
      emotional sensitization, and interpersonal sensitization. The purpose of framing
      the review in terms of pain sensitivity in fibromyalgia is to highlight that
      different mechanisms of sensitization are appropriately regarded as intervening
      variables when it comes to understanding individual differences in the experience
      of pain. The paper concludes by considering the implications of the findings of
      the review for explanations of fibromyalgia pain by nurses working in
      multidisciplinary teams. The trend appears to be able to explain the cause of
      fibromyalgia pain in terms of sensitization per se. The recommended alternative
      is to explain fibromyalgia pain in terms of changes in pain sensitivity and the
      role of underlying neural and psychosocial mechanisms.

PMID- 24882031
TI  - The use of "as-needed" range orders for opioid analgesics in the management of
      pain: a consensus statement of the American Society of Pain Management Nurses and
      the American Pain Society.

PMID- 24882033
TI  - Differential time to positivity is not predictive for central line-related
      Staphylococcus aureus bloodstream infection in routine clinical care.

PMID- 24882032
TI  - Mild, moderate, and severe pain in patients recovering from major abdominal
      surgery.
AB  - Pain interferes with various activities, such as coughing, deep breathing, and
      ambulation, designed to promote recovery and prevent complications after surgery.
      Determining appropriate cutpoints for mild, moderate, and severe pain is
      important, because specific interventions may be based on this classification.
      The purpose of this research was to determine optimal cutpoints for postoperative
      patients based on their worst and average pain during hospitalization and after
      discharge to home, and whether the optimal cutpoints distinguished patients with
      mild, moderate, or severe pain regarding patient outcomes. This secondary
      analysis consisted of 192 postoperative patients aged >=60 years. Multivariate
      analyses of variance were used to stratify the sample into mild, moderate, and
      severe pain groups using eight cutpoint models for worst and average pain in the
      last 24 hours. One-way analyses of variance were conducted to determine whether
      patients experiencing mild, moderate, or severe pain were different in outcome.
      Optimal cutpoints were similar to those previously reported, with the boundary
      between mild and moderate pain ranging from 3 to 4 and the boundary between
      moderate and severe pain ranging from 5 to 7. Worst pain cutpoints were most
      useful in distinguishing patients regarding fatigue, depression, pain's
      interference with function, and morphine equivalent administered in the previous
      24 hours. A substantial proportion of patients experienced moderate to severe
      pain. The results suggest a narrow boundary between mild and severe pain that
      interferes with function. The findings indicate that clinicians should seek to
      aggressively manage postoperative pain ratings greater than 3. 

PMID- 24882034
TI  - Characterization of lysosome-destabilizing DOPE/PLGA nanoparticles designed for
      cytoplasmic drug release.
AB  - Polymeric nanoparticles (NPs) offer a promising approach for therapeutic
      intracellular delivery of proteins, conventionally hampered by short half-lives,
      instability and immunogenicity. Remarkably, NPs uptake occurs via endocytic
      internalization leading to NPs content's release within lysosomes. To overcome
      lysosomal degradation and achieve NPs and/or loaded proteins release into
      cytosol, we propose the formulation of hybrid NPs by adding 1,2-dioleoyl-sn
      glycero-3-phosphoethanolamine (DOPE) as pH sensitive component in the formulation
      of poly-lactide-co-glycolide (PLGA) NPs. Hybrid NPs, featured by different
      DOPE/PLGA ratios, were characterized in terms of structure, stability and lipid
      organization within the polymeric matrix. Experiments on NIH cells and rat
      primary neuronal cultures highlighted the safety profile of hybrid NPs. Moreover,
      after internalization, NPs are able to transiently destabilize the integrity of
      lysosomes in which they are taken up, speeding their escape and favoring
      cytoplasmatic localization. Thus, these DOPE/PLGA-NPs configure themselves as
      promising carriers for intracellular protein delivery. 

PMID- 24882035
TI  - Design of transparent film-forming hydrogels of tolterodine and their effects on
      stratum corneum.
AB  - A transparent film-forming hydrogel formulation for tolterodine was developed
      using ternary phase diagram and Box-Behnken design (BBD). Carbopol 980
      (neutralized by triethanolamine), hydroxypropyl cellulose (HPC), hydroxypropyl
      methyl cellulose (HPMC) and Tween 80 were used as matrices. Solvent was the
      mixture of water and ethyl alcohol. The measured 24 h cumulative drug release
      rate (86.02%) was consistent with the predicted value (85.42%) in mice. Steady
      state flux (J) of tolterodine in optimized formulation across rat full skin,
      epidermal, dermis and subcutaneous tissue were 15.83, 18.55, 37.15 and 81.82 MUg
      cm(-2) h(-1), respectively. Fourier transform infrared spectroscopy (FTIR) and
      differential scanning calorimetry (DSC) results suggested that the hydrogels
      could impact lipid status in SC, which was consistent with Ea (8.638 kcal/mol) of
      tolterodine from optimized formulation in rats. In the pharmacokinetic studies,
      sustained-release over 24 h and absolute bioavailability of the hydrogels
      (24.53%) was higher than tolterodine tablets (15.16%) in rats. The hydrogels were
      suitable for systemic administration of tolterodine for the treatment of
      overactive bladder.

PMID- 24882036
TI  - In vitro and in vivo evaluation of chitosan graft glyceryl monooleate as peroral
      delivery carrier of enoxaparin.
AB  - In this paper a novel copolymer, chitosan graft glyceryl monooleate (CS-GO) was
      synthesized and its potential as the nanocarrier for enhancing the peroral
      delivery of enoxaparin was studied systemically. The successful synthesis was
      characterized by (1)H NMR. Enoxaparin nanocomplexes were prepared by self
      assembly. Mucoadhesive properties of the nanocomplexes were evaluated using mucin
      particle method. Uptake and transport of the nanocomplexes were investigated in
      Caco-2 cells. In vivo absorption was studied in rats. The therapeutic effects of
      the nanocomplexes were evaluated using pulmonary thromboembolism model in mice.
      This study demonstrated that compared to chitosan based system, hydrophobic
      modification of CS with GO enhanced the oral absorption of enoxaparin
      significantly, which is in good agreement with the enhanced mucoadhesion,
      cellular internalization and transport in cell culture. Cellular uptake of CS-GO
      based enoxaparin nanocomplexes was incubation time, enoxaparin concentration and
      incubation temperature dependent. The uptake mechanism was assumed to be
      adsorptive endocytosis via clathrin- and caveolae-mediated process. Its
      therapeutic efficacy was further demonstrated by pharmacodynamic study with
      pulmonary thromboembolism inhibition percentage 47.1%. In conclusion, CS-GO
      copolymer is a promising nanocarrier for enhancing the oral absorption of
      enoxaparin. 

PMID- 24882037
TI  - Development and comparison of intramuscularly long-acting paliperidone palmitate
      nanosuspensions with different particle size.
AB  - The main purpose of this study was to develop and compare the pharmacokinetic
      behavior of two paliperidone palmitate (PP) nanosuspensions with different
      particle size after intramuscular (i.m.) administration. PP nanosuspensions were
      prepared by wet media milling method and the mean particle size of nanosuspension
      was controlled as 1,041 +/- 6 nm (A) and 505 +/- 9 nm (B), respectively. The
      morphology of nanosuspensions was observed by scanning electron microscope (SEM).
      Differential scanning calorimeter (DSC) and powder X-ray diffraction (PXRD)
      confirmed the crystallinity of PP in nanosuspensions. The physical and chemical
      stabilities of nanosuspensions A and B were investigated by particle analyzer and
      HPLC after storage for 2 months at 25 degrees C, 4 degrees C and mechanical
      shaking condition. No obvious change in particle size and chemical degradation of
      drug were observed. Following single-dose i.m. administration to beagle dogs, the
      release of paliperidone lasted for nearly 1 month. The Tmax of nanosuspensions A
      and B was 6 (d) and 10 (d). The AUC0-t and Cmax of nanosuspensions A was 2.0-fold
      and 1.8-fold higher than nanosuspensions B (p<0.05). The results demonstrated
      that PP nanosuspensions formulation had long-acting effect. Nanosuspension A with
      a larger particle size performed better than nanosuspension B. As a result, it is
      important to design appropriate particle size of nanosuspensions for i.m.
      administration in order to produce larger therapeutic effect.

PMID- 24882038
TI  - Oral sustained-release suspension based on a novel taste-masked and mucoadhesive
      carrier-ion-exchange fiber.
AB  - The purpose of this study was to evaluate the feasibility of ion-exchange fiber
      ZB-1 as a novel carrier in oral taste-masked mucoadhesive sustained-release
      suspensions. Propranolol (PPN) hydrochloride was selected as a model drug with
      good water solubility, short half life and bitter taste. The PPN-fiber complexes
      (PF) were prepared by a batch process and coated with Eudragit((r)) RS100. Gamma
      scintigraphy was performed on fasted volunteers revealed about 30% ZB-1 and more
      than 50% coated ZB-1 were still remaining in the stomach at 6h. In vitro results
      showed the releases of PF and coated PPN-fiber complexes (C-PF) were sustained.
      The release, drug content and particle size of C-PF were influenced by coat to
      core ratio, concentration of coating material and rotation rate. The suspension
      was stable after standing for 30 days in 0.5% Carbopol((r)) with no release rate
      and taste changed. The administration of C-PF suspension to rats resulted a
      significant different (P<0.05) improvement of the plasma drug level and
      prolongation of the release. However, because of the burst effect, the Cmax
      values of PF suspension didn't differ from drug solution (P>0.05). Furthermore, a
      linear relationship between in vitro dissolution and in vivo absorption was
      observed.

PMID- 24882039
TI  - Enhancement of solubility, antioxidant ability and bioavailability of taxifolin
      nanoparticles by liquid antisolvent precipitation technique.
AB  - Taxifolin is a kind of flavanonol, whose antioxidant ability is superior to that
      of ordinary flavonoids compounds owing to its special structure. However, its low
      bioavailability is a major obstacle for biomedical applications, so the
      experiment is designed to prepare taxifolin nanoparticles by liquid antisolvent
      precipitation (LAP) to improve its bioavailability. We selected ethanol as
      solvent, deionized water as antisolvent, and investigated primarily the type of
      surfactant and adding amount, drug concentration, volume ratio of antisolvent to
      solvent, precipitation temperature, dropping speed, stirring speed, stirring time
      factors affecting drug particles size. Results showed that the poloxamer 188 was
      selected as the surfactant and the particle size of taxifolin obviously reduced
      with the increase of the poloxamer 188 concentration, the drug concentration and
      the dropping speed from 0.08% to 0.45%, from 0.04 g/ml to 0.12 g/ml, from 1
      ml/min to 5 ml/min, respectively, when the volume ratio of antisolvent to solvent
      increased from 2.5 to 20, the particle size of taxifolin first increased and then
      decreased, the influence of precipitation temperature, stirring speed, stirring
      time on particle size were not obvious, but along with the increase of mixing
      time, the drug solution would separate out crystallization. The optimum
      conditions were: the poloxamer 188 concentration was 0.25%, the drug
      concentration was 0.08 g/ml, the volume ratio of antisolvent to solvent was 10,
      the precipitation temperature was 25  degrees C, the dropping speed was 4 ml/min,
      the stirring speed was 800 r/min, the stirring time was 5 min. Taxifolin
      nanosuspension with a MPS of 24.6 nm was obtained under the optimum conditions.
      For getting taxifolin nanoparticles, the lyophilization method was chosen and
      correspondingly gamma-cyclodextrin was selected as cryoprotectant from gamma
      cyclodextrin, mannitol, lactose, glucose. Then the properties of raw taxifolin
      and taxifolin nanoparticles were characterized by scanning electron microscopy
      (SEM), fourier-transform infrared spectroscopy (FTIR), high performance liquid
      chromatography-mass spectrometry (LC-MS), X-ray diffraction (XRD), differential
      scanning calorimetry (DSC), and thermo gravimetric (TG), and the conclusion was
      drawn that taxifolin nanoparticles can be converted into an amorphous form but
      its chemical construction cannot been changed. Furthermore, dissolving capability
      test, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging activity and
      reducing power assay, solvent residue test were also carried out. The
      experimental data showed that the solubility and the dissolution rate of
      taxifolin nanoparticles were about 1.72 times and 3 times of raw taxifolin, the
      bioavailability of taxifolin nanoparticles increased 7 times compared with raw
      taxifolin, and the antioxidant capacity of taxifolin nanoparticles was also
      superior to raw taxifolin. Furthermore, the residual ethanol of the taxifolin
      nanoparticles was less than the ICH limit for class 3 solvents of 5000 ppm or
      0.5% for solvents and could be used for pharmaceutical. These results suggested
      that taxifolin nanoparticles might have potential value to become a new oral
      taxifolin formulation with high bioavailability.

PMID- 24882042
TI  - The efficacy of Acanthamoeba cyst kill and effects upon contact lenses of a novel
      ultraviolet lens disinfection system.
AB  - PURPOSE: To assess the efficacy of a novel ultraviolet (UV) lens device on the
      killing of Acanthamoeba cysts and the impact of efficacious doses of UV upon soft
      contact lens parameter and material characteristics. DESIGN: Prospective, in
      vitro, experimental study of a device. METHODS: A UV lens device was constructed
      and used to expose Acanthamoeba cysts to various levels of UV irradiation. Once
      an efficacious dose, as defined by a greater than 3 log reduction, was determined
      (130 mJ/cm(2)), 6 soft contact lens materials (etafilcon A, senofilcon A,
      galyfilcon A, lotrafilcon A, polymacon, and comfilcon A) were exposed to that
      dose for 30 cycles and tested for visual parameters, mechanical parameters, and
      cytotoxicity. RESULTS: The UV device produced an average log reduction of over
      3.5 log of Acanthamoeba cysts when the lens and solution inside of the inset case
      was irradiated with 130 mJ per cm(2) of UV or greater. After 30 cycles of 130 mJ
      per cm(2) UV dose each, no gross changes were observed in mechanical properties
      or cytotoxicity tests in any soft contact lenses tested. In visual parameters,
      polymacon and lotrafilcon A exhibited a shift in sphere power and diameter,
      respectively. CONCLUSIONS: The novel UV lens device was able to provide a marked
      log reduction to Acanthamoeba cysts, one of the most resistant ocular disease
      causing organisms found in lens cases, without a detrimental effect on many lens
      materials.

PMID- 24882040
TI  - DNA and aptamer stabilized gold nanoparticles for targeted delivery of anticancer
      therapeutics.
AB  - Gold nanoparticles (GNPs) can be used as carriers of a variety of therapeutics.
      Ideally, drugs are released in the target cells in response to cell specific
      intracellular triggers. In this study, GNPs are loaded with doxorubicin or
      AZD8055, using a self-immolative linker which facilitates the release of
      anticancer therapeutics in malignant cells without modifications of the active
      compound. An additional modification with the aptamer AS1411 further increases
      the selectivity of GNPs towards cancer cells. Both modifications increase
      targeted delivery of therapeutics with GNPs. Whereas GNPs without anticancer
      drugs do not affect cell viability in all cells tested, AS1411 modified GNPs
      loaded with doxorubicin or AZD8055 show significant and increased reduction of
      cell viability in breast cancer and uveal melanoma cell lines. These results
      highlight that modified GNPs can be functionalized to increase the efficacy of
      cancer therapeutics and may further reduce toxicity by increasing targeted
      delivery towards malignant cells. 

PMID- 24882041
TI  - Cytomorphological changes and susceptibility of clinical isolates of Acanthamoeba
      spp. to heterocyclic alkylphosphocholines.
AB  - The treatment of diseases caused by pathogenic strains of Acanthamoeba spp. is to
      date limited and frequently unsuccessful. Alkylphosphocholines (APCs) are
      promising agents with interesting results of antiparasitic activity in
      experimental and clinical conditions. In the present study susceptibilities of
      two clinical isolates of Acanthamoeba spp. to four heterocyclic APCs were
      investigated. The isolates showed high degrees of susceptibility to studied APCs
      and all the tested concentrations inhibited the growth with the highest
      concentrations of 500-1000MUM causing 100% eradication of the trophozoites and
      cysts. The highest susceptibility was noted in IF16-P-4-Pip with EC50 values of
      28.62-43.73MUM, and EC90 values of 30.70-63.16MUM after 48h of incubation. The
      cytomorphological changes of trophozoites after the exposure to APCs included
      rounding up of cells, resorption of acanthopodia and subsequent lysis. The
      remains of cells were typical with oval shape and identifiable nucleus. After the
      application of IF16-P-4-Pip, IF16-P-2-MetPip, and IF16-P-Azep, at concentrations
      of 62.5-125MUM to trophozoite suspension, a formation of pseudocysts was
      detected. The single-layered coat covering the surface of pseudocyst stained
      positively with a fluorescence brightener, Rylux. Destroyed cysts were
      characteristic with shrinkage of the cytoplasm and separation of the cytoplasmic
      membrane from the endocyst. IF16-P-2-MetPip at the highest concentration formed
      large spherical vesicles which frequently enclosed inactivated cysts.
      Heterocyclic APCs used in the study demonstrated strong amoebicidal activity and
      the cytotoxic effect of IF16-P-4-Pip similar to that of miltefosine indicates its
      possible therapeutic potential. 

PMID- 24882043
TI  - A tetravalent alphavirus-vector based dengue vaccine provides effective immunity
      in an early life mouse model.
AB  - Dengue viruses (DENV1-4) cause 390 million clinical infections every year,
      several hundred thousand of which progress to severe hemorrhagic and shock
      syndromes. Preexisting immunity resulting from a previous DENV infection is the
      major risk factor for severe dengue during secondary heterologous infections.
      During primary infections in infants, maternal antibodies pose an analogous risk.
      At the same time, maternal antibodies are likely to prevent induction of
      endogenous anti-DENV antibodies in response to current live, attenuated virus
      (LAV) vaccine candidates. Any effective early life dengue vaccine has to overcome
      maternal antibody interference (leading to ineffective vaccination) and poor
      induction of antibody responses (increasing the risk of severe dengue disease
      upon primary infection). In a previous study, we demonstrated that a non
      propagating Venezuelan equine encephalitis virus replicon expression vector
      (VRP), expressing the ectodomain of DENV E protein (E85), overcomes maternal
      interference in a BALB/c mouse model. We report here that a single immunization
      with a tetravalent VRP vaccine induced NAb and T-cell responses to each serotype
      at a level equivalent to the monovalent vaccine components, suggesting that this
      vaccine modality can overcome serotype interference. Furthermore, neonatal
      immunization was durable and could be boosted later in life to further increase
      NAb and T-cell responses. Although the neonatal immune response was lower in
      magnitude than responses in adult BALB/c mice, we demonstrate that VRP vaccines
      generated protective immunity from a lethal challenge after a single neonatal
      immunization. In summary, VRP vaccines expressing DENV antigens were immunogenic
      and protective in neonates, and hence are promising candidates for safe and
      effective vaccination in early life. 

PMID- 24882044
TI  - Should we treat patients with impaired consciousness and periodic patterns on
      EEG?
AB  - PURPOSE: The significance of periodic EEG patterns in patients with impaired
      consciousness is controversial. We aimed to determine if treating these patterns
      influences clinical outcome. METHOD: We studied all patients who had periodic
      discharges on their EEG recordings from January 2007 to December 2009. Patients
      with clinical seizures within the preceding 24h, or with unequivocal
      electrographical seizure activity were excluded. Logistic regression was
      performed to analyze for factors associated with (a) mortality (b) functional
      status (c) resolution of EEG pattern. RESULTS: Of the 4246 patients who had EEG,
      111 (2.6%) had periodic EEG patterns. 64 met inclusion criteria. In adjusted
      analysis, higher mortality was associated with acute symptomatic etiology (OR
      17.74, 95% CI 1.61-196.07, p=0.019), and presence of clinical seizures (OR 4.73,
      95% CI 1.10-20.34, p=0.037). For each unit decrement of GCS, the odds of
      inpatient mortality and a poorer functional state on discharge increased by 23%
      (95% CI 7-37%, p=0.009) and 33% (95% CI 9-51%, p=0.011) respectively.
      Administration of abortive therapy was an independent risk factor for poorer
      functional status on discharge (adjusted OR 41.39, 95% CI 2.88-594.42, p=0.006),
      while patients with history of pre-existing cerebral disease appeared more likely
      to return to baseline functional status on discharge (unadjusted OR 5.00, 95% CI
      1.40-17.86, p=0.013). CONCLUSION: Treatment of periodic EEG patterns does not
      independently improve clinical outcome of patients with impaired conscious
      levels. Occurrence of seizures remote to the time of EEG and lower GCS scores
      independently predict poor prognoses.

PMID- 24882045
TI  - Sling left pulmonary artery with patent type IIA tracheobronchial anomaly and
      imperforate anus.
AB  - We present a 3-month-old boy with a type IIA sling left pulmonary artery
      associated with imperforate anus and rectourethral fistula. Tracheobronchial
      abnormalities are demonstrated using multidetector CT with 3-D volume rendering
      of the airways. This case represents a novel variant of an already rare entity
      with an unusually high right upper lobe bronchus and no evidence of associated
      tracheobronchial stenosis. 

PMID- 24882046
TI  - [Autosomal dominant osteopetrosis: a presentation of 3 cases and a new gene
      mutation].
AB  - Osteopetrosis (OP) is a congenital bone disease which is caused by a functional
      disorder in osteoclasts with inability for normal bone resorption, leading to
      increased bone mineral density and bone sclerosis. It can be classified into
      different groups according to their clinical and their genetic characteristics:
      autosomal recessive with several subtypes (OPTB) or autosomal dominant type 1 or
      2 (OPTA1-2). There is a wide clinical variability of the disease, from
      asymptomatic to lethal in the first months of life, with variable expressivity in
      the family members. Diagnosis is mainly clinical with genetic confirmation of the
      OP, and treatment is symptomatic. Three cases of OP are presented, with the
      discovery of a new gene mutation in LRP5 which caused OPTA1 in one of them. 

PMID- 24882047
TI  - [Epidural abscess and frontal sinusitis].

PMID- 24882048
TI  - Role of a 48-week pegylated interferon therapy in hepatitis B e antigen positive
      HIV-co-infected patients on cART including tenofovir: EMVIPEG study.
AB  - BACKGROUND & AIMS: In hepatitis B e antigen (HBeAg) positive-HIV co-infected
      patients treated with combined antiretroviral therapy (cART), including tenofovir
      disoproxil fumarate (TDF), the rate of HBe seroconversion remains low. Whether
      adding pegylated interferon alfa (PegIFN) could increase the likelihood of HBeAg
      loss and HBe seroconversion has not been assessed. METHODS: A 48-week PegIFN
      therapy was added to HBeAg positive-HIV co-infected patients on TDF and
      emtricitabine, or lamivudine for at least 6 months. The primary endpoint was HBV
      sustained response: HBe seroconversion with undetectable HBV DNA levels 24 weeks
      after completing PegIFN therapy (W72). RESULTS: Fifty-one patients (49 men,
      median age 46 years, range: 32-65), were included. Median duration of HIV, HBV
      infections and TDF therapy was 10.3 (0.6-22), 9.8 (0.5-16), and 3.3 (0.5
      6.8)years, respectively. Median baseline CD4 count was 506 (175-1316)/mm(3). HIV
      viral load was <50 copies/ml in 49 (96%) patients. Nine (18%) patients stopped
      PegIFN prematurely. Ten (20%) patients experienced HBeAg loss at W72 and four
      (8%) patients had a HBV sustained response. No HBs seroconversion was observed.
      Only patients with more than 350 CD4/mm(3) at baseline achieved HBe loss. HBeAg
      level >10 PEIU/ml at W12 or a quantitative HBsAg decline <0.5 log IU/ml at W24
      had 100% and 84% negative predictive values for response, respectively.
      CONCLUSIONS: 48-week PegIFN additional therapy to cART including TDF did not
      significantly increase the HBe seroconversion rate, despite an HBeAg loss in 20%
      of the patients. HBe and HBs kinetics may nevertheless be of help in tailoring
      and optimising this strategy.

PMID- 24882049
TI  - Role of interleukin 10 in norfloxacin prevention of luminal free endotoxin
      translocation in mice with cirrhosis.
AB  - BACKGROUND & AIMS: Bacterial endotoxin is present in patients with advanced
      cirrhosis and can induce an immunogenic response without an overt infection.
      Norfloxacin is a gram-negative bactericidal drug able to maintain low endotoxin
      levels and stimulate IL-10 production. We aimed at investigating the role of IL
      10 in decreasing endotoxin absorption in cirrhotic mice treated with norfloxacin.
      METHODS: Cirrhosis was induced by carbon tetrachloride or bile duct ligation in
      wild type and IL10-deficient mice with or without norfloxacin prior to an
      intragastrical administration of E. coli, K. pneumonia or E. faecalis.
      Spontaneous and induced bacterial translocation, free endotoxin and cytokine
      levels were evaluated in mesenteric lymph nodes. Intestinal permeability was
      followed by fluorimetry and barrier integrity markers were measured in disrupted
      intestinal samples. The inflammatory-modulating mechanism was characterized in
      purified intestinal mononuclear cells. RESULTS: Norfloxacin reduced spontaneous
      and induced MLN positive-cultures in wild type and IL-10-deficient animals.
      However, reduction of free endotoxin levels was associated with norfloxacin in
      wild type but not in IL-10-deficient mice. Wild type but not IL-10-deficient mice
      treated with norfloxacin significantly normalized intestinal permeability and
      improved gut barrier integrity markers. The toll-like receptor 4-mediated pro
      inflammatory milieu was modulated by norfloxacin in a concentration-dependent
      manner in cultured intestinal mononuclear cells of wild type mice but not of IL
      10-deficient mice. The restoration of IL-10 levels in IL-10-deficient animals
      reactivated the norfloxacin effect on inflammatory-modulation, gut barrier
      permeability, and luminal endotoxin absorption. CONCLUSION: Norfloxacin not only
      reduces gram-negative intestinal flora but also participates in an IL-10-driven
      modulation of gut barrier permeability, thus reducing luminal free endotoxin
      absorption in experimental cirrhosis.

PMID- 24882050
TI  - Intrahepatic regulatory T cells in autoimmune hepatitis are associated with
      treatment response and depleted with current therapies.
AB  - BACKGROUND & AIMS: Autoimmune hepatitis (AIH) is a chronic autoimmune liver
      disease usually requiring life-long immunosuppression. The mechanisms for disease
      initiation and chronicity are largely unknown. A contribution of deficient
      regulatory T cells (Tregs) in the blood was controversially discussed recently.
      So far investigations in the target organ have been limited to single parameter
      analysis in untreated AIH. METHODS: We retrospectively analysed the pattern of
      liver infiltrating T, B and regulatory T cells quantitatively with simultaneous
      multicolour immunofluorescence before (n=45) and under (n=31) therapy in adult
      AIH type 1 (AIH-1) patients. RESULTS: Intrahepatic CD4(+) cells dominate over
      CD8(+) at diagnosis, but with increasing disease activity the CD4(+)/CD8(+) ratio
      approached one. While there is no change of Tregs in the blood, they are enriched
      with effector T cells (Teffs) within the liver of patients with untreated AIH-1
      with a constant Treg/Teff ratio. Even more importantly, immunosuppression mostly
      with steroids and azathioprine caused a disproportional loss of intrahepatic
      Tregs. Patients reaching biochemical remission had higher intrahepatic Treg/Teff
      and Treg/B cell ratios compared to patients failing to reach remission. In vitro
      proliferation of Tregs seemed to be more suppressed by prednisolone than
      expansion of Teffs. Furthermore, intraportal B cells correlated with serum IgG
      suggesting an autochthonous intrahepatic IgG production. CONCLUSIONS:
      Intrahepatic Tregs are rather enriched than numerically deficient in untreated
      AIH-1. The disproportional decrease of intrahepatic Tregs during therapy might
      explain high relapse rates after discontinuation of immunosuppression. Thus,
      future therapies increasing intrahepatic immunoregulation might be better suited
      for long-term control of AIH.

PMID- 24882052
TI  - Liver transplantation and severe acute alcoholic hepatitis: an ethical
      consideration.

PMID- 24882051
TI  - Chronic HCV infection increases cardiac left ventricular mass index in
      normotensive patients.
AB  - BACKGROUND & AIMS: Left ventricular hypertrophy (LVH), is an independent
      predictor for cardiovascular events. We investigated if chronic hepatitis C virus
      (HCV) infection and the related insulin resistance (IR)/hyperinsulinemia could
      influence the increase of left ventricular mass (LVM). METHODS: We enrolled 260
      outpatients matched for age, body mass index, gender, ethnicity: 52 with never
      treated uncomplicated chronic HCV infection (HCV(+)), 104 never-treated
      hypertensives (HT) and 104 healthy subjects (NT). LVM was calculated according to
      the Devereux formula and indexed for body surface area. The following laboratory
      parameters were measured: fasting plasma glucose and insulin, total, LDL- and HDL
      cholesterol, triglyceride, creatinine, e-GFR-EPI, HOMA. Quantitative HCV-RNA was
      assessed by PCR. RESULTS: HCV(+) patients with respect to healthy normotensive
      subjects had an increased LVMI (100 +/- 23 vs. 83 +/- 15 g/m(2); p < 0.0001),
      similar to that observed in HT group (103 +/- 25 g/m(2)). Regarding biochemical
      variables, HCV(+) patients, in comparison with normotensive healthy subjects, had
      higher triglyceride, creatinine, fasting insulin and HOMA (3.2 +/- 1.3 vs. 2.5 +/
      1.0; p < 0.0001). At linear regression analysis, the correlation between LVMI
      and HOMA was similar in HT (r = 0.528, p < 0.0001) and HCV(+) (r = 0.489, p <
      0.0001) groups. At multiple regression analysis, HOMA resulted the major
      determinant of LMVI in all groups, explaining respectively 21.8%, 27.8%, and
      23.9% of its variation in NT, HT and HCV(+). At correlational analysis HCV-RNA
      and HOMA demonstrated a strong and linear relationship between them, explaining
      the 72.4% of their variation (p = 0.022). CONCLUSIONS: We demonstrated a
      significant and direct correlation between HOMA and LVMI in patients with chronic
      HCV infection, similar to that observed in hypertensives.

PMID- 24882053
TI  - Reply to: "liver transplantation and severe acute alcoholic hepatitis: an ethical
      consideration".

PMID- 24882054
TI  - Adiponectin protects against acetaminophen-induced mitochondrial dysfunction and
      acute liver injury by promoting autophagy in mice.
AB  - BACKGROUND & AIMS: Acetaminophen (APAP) overdose causes hepatic necrosis and
      acute liver injury by inducing mitochondrial dysfunction and damage. Although the
      biochemical pathways that mediate APAP-induced hepatotoxicity have been well
      studied, the body's defense mechanism to attenuate this disease remains elusive.
      This study investigated the roles of adiponectin, an adipocyte-secreted adipokine
      with pleiotropic protective effects against obesity-related metabolic
      dysfunction, in the pathogenesis of APAP-induced liver injury in mice. METHODS:
      Adiponectin knockout (ADN KO) and C57 wild type mice were treated with an
      overdose of APAP, followed by histological and biochemical evaluation of liver
      injury and activation of autophagy. The mechanism of adiponectin in APAP-induced
      hepatocytic toxicity was also explored in primary cultured hepatocytes. RESULTS:
      APAP overdose triggers a marked accumulation of adiponectin in injured liver
      tissues. ADN KO mice exhibit severely exacerbated mitochondrial dysfunction and
      damage, oxidative stress and necrosis and much higher mortality in response to
      APAP overdose, whereas these changes are reversed by a single injection of
      adiponectin. Mechanistically, adiponectin induces autophagosome formation by AMP
      activated protein kinase (AMPK)-dependent activation of the Unc-51-like kinase 1,
      consequently leading to the removal of damaged mitochondria from hepatocytes. The
      protective effects of adiponectin against APAP-induced mitochondrial damage,
      oxidative stress and necrosis are abrogated by blockage of AMPK or
      pharmacological inhibition of autophagy. CONCLUSIONS: Our findings suggest that
      the APAP-induced accumulation of adiponectin in liver tissues serves as an
      adaptive mechanism to ameliorate hepatotoxicity by promoting autophagy-mediated
      clearance of damaged mitochondria. Adiponectin agonists may represent a promising
      therapy for the drug-induced acute liver failure.

PMID- 24882056
TI  - Nanocrystalline Ag microflowers as a versatile SERS platform.
AB  - In this paper, the synthesis of Ag microflowers for use as manipulable and
      reusable substrates in surface enhanced Raman spectroscopy (SERS) is
      demonstrated, working with ultra-low volumes of the analyte. Flower-like AgBr
      crystallites with a growth direction of <110> were first obtained by thermolysing
      a complex obtained by the stabilization of (AgCl2)(-) anions with
      tetraoctylammonium bromide. NaBH4 reduction leads to the formation of porous Ag
      microflowers (50-100 MUm) with interconnected nanoparticles. The coupling of the
      nanoparticles in the microflower results in broadband extinction from visible to
      IR wavelengths, facilitating SERS using both red and green wavelengths. Using
      thiophenol as test analyte, uniform SERS enhancement factors in the range of
      10(6)-10(8) have been achieved from different parts of the microflower. The
      microflowers have been used for labeled and non-labeled detection of both single-
      and double-stranded DNA and using simple manipulation techniques, SERS data have
      been collected from ultra-low volumes of the analyte solution (~0.34 nL). The
      reusability of the substrate for SERS over multiple cycles involving a rapid and
      efficient wet chemical cleaning procedure is also demonstrated. Finally, by
      placing the microflower in a microfluidic device, chemical reactions have been
      examined in situ. 

PMID- 24882057
TI  - Discovery methodology for the development of direct factor VIIa inhibitors.
AB  - INTRODUCTION: Heparin and warfarin have historically been the only
      antithrombotics available. Recently, however, newer anticoagulants have been
      developed. Factor VIIa (fVIIa) inhibitors represent one of the new and
      potentially exciting classes of anticoagulants currently under development.
      Indeed, several methodologies have been used to develop fVIIa inhibitors. AREAS
      COVERED: The authors highlight some of the methologies applied for the discovery
      of fVIIa inhibitors including phage display, isolation of endogenous peptides
      from hematophagous animals and the use of the 1,5-benzothiazepine molecular
      scaffolds and screens of large chemical libraries previously used to identify
      other serine protease inhibitors. Although these screens were intended to
      identify thrombin and factor Xa inhibitors, the compounds often had concomitant
      fVIIa activity. The authors also discuss the utilization of medical chemistry
      techniques for the discovery of these compounds. EXPERT OPINION: FVIIa inhibitors
      represent a viable option for the development of new anticoagulants. There are
      theoretical advantages that fVIIa inhibitors may possess over existing
      anticoagulants and highly specific inhibitors that possess oral bioavailability
      and low bleeding risk may succeed.

PMID- 24882058
TI  - Highly sensitive immunoassay based on controlled rehydration of patterned
      reagents in a 2-dimensional paper network.
AB  - We have demonstrated a multistep 2-dimensional paper network immunoassay based on
      controlled rehydration of patterned, dried reagents. Previous work has shown that
      signal enhancement improves the limit of detection in 2-dimensional paper network
      assays, but until now, reagents have only been included as wet or dried in
      separate conjugate pads placed at the upstream end of the assay device. Wet
      reagents are not ideal for point-of-care because they must be refrigerated and
      typically limit automation and require more user steps. Conjugate pads allow
      drying but do not offer any control of the reagent distribution upon rehydration
      and can be a source of error when pads do not contact the assay membrane
      uniformly. Furthermore, each reagent is dried on a separate pad, increasing the
      fabrication complexity when implementing multistep assays that require several
      different reagents. Conversely, our novel method allows for consistent,
      controlled rehydration from patterned reagent storage depots directly within the
      paper membrane. In this assay demonstration, four separate reagents were
      patterned in different regions of the assay device: a gold-antibody conjugate
      used for antigen detection and three different signal enhancement components that
      must not be mixed until immediately before use. To show the viability of
      patterning and drying reagents directly onto a paper device for dry reagent
      storage and subsequent controlled release, we tested this device with the malaria
      antigen Plasmodium falciparum histidine-rich protein 2 (PfHRP2) as an example of
      target analyte. In this demonstration, the signal enhancement step increases the
      visible signal by roughly 3-fold and decreases the analytical limit of detection
      by 2.75-fold. 

PMID- 24882059
TI  - How different types of users develop trust in technology: a qualitative analysis
      of the antecedents of active and passive user trust in a shared technology.
AB  - The aim of this study was to investigate the antecedents of trust in technology
      for active users and passive users working with a shared technology. According to
      the prominence-interpretation theory, to assess the trustworthiness of a
      technology, a person must first perceive and evaluate elements of the system that
      includes the technology. An experimental study was conducted with 54 participants
      who worked in two-person teams in a multi-task environment with a shared
      technology. Trust in technology was measured using a trust in technology
      questionnaire and antecedents of trust were elicited using an open-ended
      question. A list of antecedents of trust in technology was derived using
      qualitative analysis techniques. The following categories emerged from the
      antecedent: technology factors, user factors, and task factors. Similarities and
      differences between active users and passive user responses, in terms of trust in
      technology were discussed. 

PMID- 24882060
TI  - Delivering meat carcasses/cuts to craft-butcher shops: an investigation of work
      characteristics and manual handling hazards.
AB  - This study investigated delivery scenarios of service drivers working in the
      retail meat industry. The methodology included analysis of accident reports, and
      field investigations of deliveries at craft-butcher shop premises, including semi
      structured interviews with managers and workers. The findings provide greater
      clarity about the hazards in this job, and suggest for peripatetic delivery
      activities, four main factors on which decisions about risk and good practice may
      be made: composition of the orders; characteristics of the delivery
      vehicle/truck; handling method most often used; and, the road/access conditions. 

PMID- 24882061
TI  - Improved prediction of lobar perfusion contribution using technetium-99m-labeled
      macroaggregate of albumin single photon emission computed tomography/computed
      tomography with attenuation correction.
AB  - OBJECTIVE: Lung cancer resection can require removal of an entire lobe and, at
      times, bilobectomy or pneumonectomy. Many patients will also have significantly
      compromised lung function that requires limiting the extent of surgery or could
      preclude surgery altogether. The preoperative assessment should include predicted
      postoperative forced expiratory volume in 1 second (ppoFEV1), because a ppoFEV1
      of <40% predicts significantly increased perioperative morbidity. The ppoFEV1 can
      be estimated by multiplying the preoperative FEV1 by the residual perfused
      territory percentage, as predicted on planar perfusion scintigraphy (PPS).
      However, ppoFEV1 using PPS has shown variable correlation with spirometry
      measured postoperative FEV1. METHODS: We propose an improved method for assessing
      regional lung perfusion in preoperative lung surgery patients. Patients undergo
      single photon emission computed tomography/computed tomography (SPECT/CT) imaging
      with attenuation correction using the conventional perfusion agent, technetium
      99m-labeled macroaggregate of albumin. The CT image provides information for
      manual segmentation of each lobe. These segmentations are applied to the SPECT
      images to determine lobar perfusion. This proposed method was compared with PPS.
      RESULTS: This technique was evaluated in 17 patients. As expected, the perfusion
      contributions of the right and left lungs, calculated from SPECT/CT, correlated
      closely with those obtained from PPS (Pearson r=0.995). However, the lobar
      perfusion contributions obtained by PPS and SPECT/CT were significantly
      different, by 2 methods of comparison (Hotelling's P=1.7*10(-6) and P=1.7*10(
      4)). CONCLUSIONS: This new SPECT/CT technique provides an anatomically more
      accurate assessment of lobar perfusion. This technique can refine which patients
      should be operative candidates and allow better prediction of postoperative
      function in contrast to the anatomically inaccurate planar scintigraphic
      predictions, which often underestimate the postoperative FEV1. This new technique
      is expected to have a significant effect on the resectability of patients with
      lung cancer.

PMID- 24882055
TI  - Stress regulates endocannabinoid-CB1 receptor signaling.
AB  - The CB1 cannabinoid receptor is a G protein coupled receptor that is widely
      expressed throughout the brain. The endogenous ligands for the CB1 receptor
      (endocannabinoids) are N-arachidonylethanolamine and 2-arachidonoylglycerol;
      together the endocannabinoids and CB1R subserve activity dependent, retrograde
      inhibition of neurotransmitter release in the brain. Deficiency of CB1 receptor
      signaling is associated with anhedonia, anxiety, and persistence of negative
      memories. CB1 receptor-endocannabinoid signaling is activated by stress and
      functions to buffer or dampen the behavioral and endocrine effects of acute
      stress. Its role in regulation of neuronal responses is more complex. Chronic
      variable stress exposure reduces endocannabinoid-CB1 receptor signaling and it is
      hypothesized that the resultant deficiency in endocannabinoid signaling
      contributes to the negative consequences of chronic stress. On the other hand,
      repeated exposure to the same stress can sensitize CB1 receptor signaling,
      resulting in dampening of the stress response. Data are reviewed that support the
      hypothesis that CB1 receptor signaling is stress responsive and that maintaining
      robust endocannabinoid/CB1 receptor signaling provides resilience against the
      development of stress-related pathologies. 

PMID- 24882062
TI  - An assessment of urea-formaldehyde fertilizer on the diversity of bacterial
      communities in onion and sugar beet.
AB  - The impact of a urea-formaldehyde (UF) fertilizer on bacterial diversity in onion
      bulbs and main roots of sugar beet were examined using a 16S rRNA gene clone
      library. The UF fertilizer markedly increased bacterial diversity in both plants.
      The results of principal coordinates analysis (PCoA) revealed that nearly 30% of
      the variance observed in bacterial diversity in both the onion and sugar beet was
      attributed to the fertilization conditions and also that the community structures
      in both plants shifted unidirectionally in response to the UF fertilizer. 

PMID- 24882063
TI  - Resveratrol counteracts lipopolysaccharide-mediated microglial inflammation by
      modulating a SOCS-1 dependent signaling pathway.
AB  - Brain damage or exposure to inflammatory agents provokes the activation of
      microglia and secretion of pro-inflammatory and neurotoxic mediators responsible
      for neuronal loss. Several lines of evidence show that resveratrol, a natural non
      flavonoid polyphenol, may exert a neuroprotective action in neurodegenerative
      diseases. Suppressor of cytokine signaling (SOCS) proteins are a family of eight
      members expressed by immune cells and the central nervous system (CNS) cells,
      that regulate immune processes within the CNS, including microglia activation. We
      demonstrate that resveratrol had anti-inflammatory effects in murine N13
      microglial cells stimulated with lipopolysaccharide (LPS), through up-regulating
      SOCS-1 expression. Interestingly, in SOCS-1-silenced cells resveratrol failed to
      play a protective role after LPS treatment. Our data demonstrate that resveratrol
      can impair microglia activation by activating a SOCS-1 mediated signaling
      pathway. 

PMID- 24882064
TI  - Two universality classes for random hyperbranched polymers.
AB  - We grow AB2 random hyperbranched polymer structures in different ways and using
      different simulation methods. In particular we use a method of ad hoc
      construction of the connectivity matrix and the bond fluctuation model on a 3D
      lattice. We show that hyperbranched polymers split into two universality classes
      depending on the growth process. For a "slow growth" (SG) process where monomers
      are added sequentially to an existing molecule which strictly avoids cluster
      cluster aggregation the resulting structures share all characteristic features
      with regular dendrimers. For a "quick growth" (QG) process which allows for
      cluster-cluster aggregation we obtain structures which can be identified as
      random fractals. Without excluded volume interactions the SG model displays a
      logarithmic growth of the radius of gyration with respect to the degree of
      polymerization while the QG model displays a power law behavior with an exponent
      of 1/4. By analyzing the spectral properties of the connectivity matrix we
      confirm the behavior of dendritic structures for the SG model and the
      corresponding fractal properties in the QG case. A mean field model is developed
      which explains the extension of the hyperbranched polymers in an athermal solvent
      for both cases. While the radius of gyration of the QG model shows a power-law
      behavior with the exponent value close to 4/5, the corresponding result for the
      SG model is a mixed logarithmic-power-law behavior. These different behaviors are
      confirmed by simulations using the bond fluctuation model. Our studies indicate
      that random sequential growth according to our SG model can be an alternative to
      the synthesis of perfect dendrimers. 

PMID- 24882065
TI  - Pyrenacantha volubilis Wight, (Icacinaceae) a rich source of camptothecine and
      its derivatives, from the Coromandel Coast forests of India.
AB  - Camptothecine, a potent eukaryotic topoisomerase inhibitor, is an important
      anticancer compound. The global demand for this compound was estimated to be $1
      billion in 2003 and is only further expected to increase. Partly to meet the
      expected increase in demand, in the recent past, several efforts have been made
      to discover newer and alternative plant and fungal sources of camptothecine. In
      this study we report a rich source of camptothecine and its natural derivatives,
      Pyrenacantha volubilis (Icacinaceae) from the eastern coast of peninsular India.
      Camptothecine and its derivatives were analyzed using high performance liquid
      chromatography (HPLC) coupled with electrospray mass spectrometry (ESI-MS) in all
      plant parts such as twigs, leaves, roots, seedling, ripened whole fruit, fruit
      coat, seed coat and cotyledons. Cotyledons and ripened whole fruits contained the
      highest amount of camptothecine (1.35% and 0.60% dry weight respectively). LC-MS
      and ESI-MS/MS analyses revealed besides camptothecine, other derivatives and
      precursors such as 10-hydroxycamptothecine, 9-methoxycamptothecine, 20
      deoxycamptothecine, deoxypumiloside, strictosidine and strictosamide. Pure
      camptothecine was isolated from fruits and structurally confirmed using NMR. Seed
      extracts were found to be effective against breast cancer, ovarian, colon and
      carcinoma cell lines (with IC50 values of 4.0 MUg/mL, 6.5 MUg/mL, 25.0 MUg/mL and
      25.0 MUg/mL respectively). We discuss the results in the context of exploring
      alternative sources of camptothecine.

PMID- 24882069
TI  - Each individual is a surprise: a conversation with Marianne Horney Eckardt.
AB  - "Each Individual is a Surprise" is a brief account of a dialogue between Marianne
      Horney Eckardt and myself about the state of psychoanalysis and the
      psychoanalytic process, the danger of idolatry, the damaging impact of
      psychoanalytic schools when they create a standardized and pathologizing approach
      to people, the value of curiosity and humility and retaining one's clinical
      creativity. The role of Rank, Horney, Sullivan, and Fromm in Dr. Eckardt's long
      life and rich work is touched upon. 

PMID- 24882068
TI  - Point-of-care biochemical assays using gold nanoparticle-implemented
      microfluidics.
AB  - One of the goals of point-of-care (POC) is a chip-based, miniaturized, portable,
      self-containing system that allows the assay of proteins, nucleic acids, and
      cells in complex samples. The integration of nanomaterials and microfluidics can
      help achieve this goal. This tutorial review outlines the mechanism of assaying
      biomarkers by gold nanoparticles (AuNPs), and the implementation of AuNPs for
      microfluidic POC devices. In line with this, we discuss some recent advances in
      AuNP-coupled microfluidic sensors with enhanced performance. Portable and
      automated instruments for device operation and signal readout are also included
      for practical applications of these AuNP-combined microfluidic chips. 

PMID- 24882066
TI  - The glycolytic enzyme, GPI, is a functionally conserved modifier of dopaminergic
      neurodegeneration in Parkinson's models.
AB  - Neurodegenerative diseases represent an increasing burden in our aging society,
      yet the underlying metabolic factors influencing onset and progression remain
      poorly defined. The relationship between impaired IGF-1/insulin-like signaling
      (IIS) and lifespan extension represents an opportunity to investigate the
      interface of metabolism with age-associated neurodegeneration. Using data sets of
      established DAF-2/IIS-signaling components in Caenorhabditis elegans, we
      conducted systematic RNAi screens in worms to select for daf-2-associated genetic
      modifiers of alpha-synuclein misfolding and dopaminergic neurodegeneration, two
      clinical hallmarks of Parkinson's disease. An outcome of this strategy was the
      identification of GPI-1/GPI, an enzyme in glucose metabolism, as a daf-2
      regulated modifier that acts independent of the downstream cytoprotective
      transcription factor DAF-16/FOXO to modulate neuroprotection. Subsequent
      mechanistic analyses using Drosophila and mouse primary neuron cultures further
      validated the conserved nature of GPI neuroprotection from alpha-synuclein
      proteotoxicity. Collectively, these results support glucose metabolism as a
      conserved functional node at the intersection of proteostasis and
      neurodegeneration. 

PMID- 24882070
TI  - The relevance of Erich Fromm.
AB  - The author stresses Fromm's role as a precursor in psychoanalysis and shows his
      connections with three scientific developments following on his death in 1980:
      the trauma literature, attachment theory and the evolution of altruism. 

PMID- 24882067
TI  - Resveratrol prevents high fat/sucrose diet-induced central arterial wall
      inflammation and stiffening in nonhuman primates.
AB  - Central arterial wall stiffening, driven by a chronic inflammatory milieu,
      accompanies arterial diseases, the leading cause of cardiovascular (CV) morbidity
      and mortality in Western society. An increase in central arterial wall
      stiffening, measured as an increase in aortic pulse wave velocity (PWV), is a
      major risk factor for clinical CV disease events. However, no specific therapies
      to reduce PWV are presently available. In rhesus monkeys, a 2 year diet high in
      fat and sucrose (HFS) increases not only body weight and cholesterol, but also
      induces prominent central arterial wall stiffening and increases PWV and
      inflammation. The observed loss of endothelial cell integrity, lipid and
      macrophage infiltration, and calcification of the arterial wall were driven by
      genomic and proteomic signatures of oxidative stress and inflammation.
      Resveratrol prevented the HFS-induced arterial wall inflammation and the
      accompanying increase in PWV. Dietary resveratrol may hold promise as a therapy
      to ameliorate increases in PWV.

PMID- 24882071
TI  - Psychoanalysis: the sacred and the profane.
AB  - Colleagues from a variety of perspectives have written about the propensity to
      enshrine psychoanalytic theory. The meaning of the word "enshrine" is to cherish
      as sacred an idea or philosophy and protect it from change. In other words, the
      way we view psychoanalysis, our theories of mind and technique, become holy writ
      and we have divided the world of theory into the sacred and the profane. This is
      the kiss of death for theory, which must constantly evolve and change, but
      comforting for the analyst who believes he is on the side of the right, the
      sacred. In this paper I will discuss how our propensity to enshrine theory has
      had a debilitating effect on the development of psychoanalysis and, in
      particular, as a treatment for the most vulnerable people who seek our help. I
      also address the idea that movement away from enshrined positions allows us to
      construct different versions of reality. In this context, the notion of "action
      at a distance" is presented along with the attendant idea of psychoanalytic
      entanglement. 

PMID- 24882072
TI  - Taste the strawberries.
AB  - The author integrates Zen Buddhist and psychoanalytic principles to introduce the
      notion of "spontaneously arising intuitive models." On the basis of the Zen
      teaching stories and patient dreams, this paper explores the meanings and psychic
      functions such intuitive models serve for patients. The notion of "the gap"
      constitutes a central organizing theme, which is elaborated in relation to
      Wilfred Bion's notion of "O." The discussion addresses issues relating to the
      uses and misuses of diagnosis and explores clinical implications. An extended
      case study exemplifies and supports the abstract concepts under discussion. 

PMID- 24882073
TI  - "Containing the uncontainable": the return of the phantom and its reconfiguration
      in ethnonational conflict resolution.
AB  - A phenomenologically informed psychoanalytic praxis for framing and conducting
      ethnonational conflict resolution in fractured communities is presented. When
      conducted with care, it begins with the polarization of each side in the conflict
      and continues into a second phase where the antagonism changes into the
      negotiation of paradox, irony and multiplicity of positions. Third, the crossing
      of mental borders with trepidation follows. Fourth, an ethic of responsibility,
      where common ground is sought brings closure to the process. A plea for humility,
      however, is required of practitioner scholars of conflict resolution because
      there is invariably a phantom that threatens to be resurrected to derail what at
      one time looked like success long after the work is formally completed. The
      return of the phantom requires practitioners to seriously consider implications
      for follow-up. 

PMID- 24882074
TI  - Silence as the voice of trauma.
AB  - Silence is a key to the unspoken world of the patient. Rather than interpreting
      silence as a defensive maneuver, the analyst may understand this disruption as a
      royal road to the patient's traumatic experiences. The author proposes to
      recognize traumatic silences in the analytic process and the transference as a re
      experiencing of past, unpredictable traumatic affective states and memories.
      Silences in this context are both a repeat of a disconnecting experience as well
      as a manifestation of a silencing identification with the original silencer. The
      clinical material illustrates effects of a German mother's World War II (WWII)
      personal traumata and collective shame-based silence on her daughter's self and
      good object development. In the daughter's analysis, the patient and the analyst,
      who herself experienced similar WWII traumata, face the pain of trauma recovery
      and un-silencing. The author suggests that the deadening effect of past traumata
      may be reversed by an analytic process of re-membering and re-speaking for both
      the patient and analyst. This allows for a more transparent, subjective
      experience in the transference and a verbal integration of ego functions. 

PMID- 24882075
TI  - Home, bitter sweet home. A psychoanalytic reading.
AB  - The paper offers a psychoanalytic reading of the popular TV series "Homeland."
      The series' manifest content centers on terrorism and counterterrorism. From a
      dynamic perspective, the viewer is invited to mistrust what is represented, and
      focus on the tension between what is projected on the screen and what remains
      hidden in the narrative's intriguing subtexts. These are: the choreography of
      internal and external reality, a recurrent theme of longing for the absent,
      idealized pre-Oedipal father, and attempts to transform memories of horror. 

PMID- 24882081
TI  - Molecular genetics and diagnosis of phenylketonuria: state of the art.
AB  - Detection of individuals with phenylketonuria (PKU), an autosomal recessively
      inherited disorder in phenylalanine degradation, is straightforward and efficient
      due to newborn screening programs. A recent introduction of the pharmacological
      treatment option emerged rapid development of molecular testing. However,
      variants responsible for PKU do not all suppress enzyme activity to the same
      extent. A spectrum of over 850 variants, gives rise to a continuum of
      hyperphenylalaninemia from very mild, requiring no intervention, to severe
      classical PKU, requiring urgent intervention. Locus-specific and genotypes
      database are today an invaluable resource of information for more efficient
      classification and management of patients. The high-tech molecular methods allow
      patients' genotype to be obtained in a few days, especially if each laboratory
      develops a panel for the most frequent variants in the corresponding population. 

PMID- 24882082
TI  - Feelings of powerlessness in individuals with either venous or diabetic foot
      ulcers.
AB  - AIM: To assess feelings of powerlessness in patients with either venous or
      diabetic foot ulcers. METHODS: This was an exploratory, descriptive, cross
      sectional study conducted from May 2010 to August 2012. Two hundred adult
      patients with either venous leg ulcers (N=100) or diabetic foot ulcers (N=100)
      were consecutively recruited from an outpatient wound care clinic of a university
      hospital in the city of Sao Paulo (Brazil). Eligibility criteria included
      patients with type 1 and 2 diabetes and foot ulcers, and those with venous leg
      ulcers and ankle-arm index between 0.8 and 1.0. Patients unable to respond to a
      questionnaire due to physical or cognitive deficit were excluded. Two instruments
      were used for data collection: a questionnaire assessing sociodemographic and
      clinical characteristics, and the Powerlessness Assessment Tool (PAT) for adult
      patients. RESULTS: Most patients were women, aged 60-70 years, and smokers. Fifty
      seven patients (57%) with diabetes had had foot ulcers for 3-6 years and 55 (55%)
      patients had had venous ulcers for 7-10 years. Wound odor and exudate were
      present in most ulcers. The total PAT score was significantly higher (P=0.002)
      for patients with foot ulcers (mean, 57.10) than for patients with venous ulcers
      (mean, 55.12). The highest mean scores for patients with venous and diabetic foot
      ulcers were 58.09 and 58.10, respectively, on the "self-perception of decision
      making capacity" domain. CONCLUSION: Patients with venous and diabetic foot
      ulcers had very strong feelings of powerlessness, but these feelings were
      significantly stronger in those with foot ulcerations.

PMID- 24882083
TI  - Pretreatment with turmeric modulates the inhibitory influence of cisplatin and
      paclitaxel on CYP2E1 and CYP3A1/2 in isolated rat hepatic microsomes.
AB  - Previous animal studies have shown that turmeric can significantly modulate the
      activity of several drug metabolizing enzymes, this may dramatically affect the
      bioavailability of several drugs resulting in over dose or less therapeutic
      effects. This study was directed to evaluate the inhibitory effects of cisplatin
      and paclitaxel on two CYP450 enzymes namely CYP2E1 and CYP3A1/2 in hepatic
      microsomes isolated from normal and turmeric pretreated rats. Cisplatin and
      paclitaxel were added by different concentrations to hepatic microsomes isolated
      from untreated and turmeric (100 mg/kg/day) pretreated rats for 15 days after
      receiving pyrazole or dexamethasone for induction of CYP2E1 and CYP3A1/2
      respectively. The kinetic potency of these drugs as CYP inhibitors was determined
      by analysis of Lineweaver-Burk plot. Addition of cisplatin or paclitaxel by (10,
      50 and 100 MUM) to hepatic microsomes from normal or turmeric pretreated rats
      caused a concentration dependent inhibition of CYP2E1, with an evidence of less
      inhibition in turmeric pretreated microsomes particularly at higher
      concentration. Both drugs at 100 MUM displayed a mixed type of inhibition of
      CYP2E1 in normal or turmeric pretreated microsomes where paclitaxel was the most
      potent inhibitor. Cisplatin (10, 50 and 100 MUM) caused a concentration dependant
      inhibition of CYP3A1/2 that was enhanced by turmeric pretreatment. The inhibition
      of CYP3A1/2 by cisplatin (100 MUM) was in non-competitive manner with a smaller
      Ki value in turmeric pretreated microsomes. The inhibitory influence of
      paclitaxel (10, 50 and 100 MUM) on CYP3A1/2 decreased with increasing the drug
      concentration and this inhibition was augmented by turmeric pretreatment.
      Interestingly, the inhibition of this enzyme by paclitaxel (10 MUM) was switched
      from mixed type in normal microsomes to competitive manner in turmeric pretreated
      ones with a marked reduction of Ki values reflecting greater inhibitory influence
      of paclitaxel on CYP3A1/2 by turmeric pretreatment. In conclusion, turmeric
      pretreatment attenuated the inhibitory influence of cisplatin and paclitaxel on
      CYP2E1 activity and magnified their inhibition on CYP3A1/2, thus the use of
      turmeric with drugs or other medications should raise concern for drugs-herb
      interactions.

PMID- 24882084
TI  - Intracellular transport of nanodiamond particles in human endothelial and
      epithelial cells.
AB  - During the recent years nanodiamonds have been the subject of interest as
      possible means of targeted delivery of anticancer substances. Detonation
      nanodiamonds are attractive candidates for intracellular studies due to their
      synthesis methods, low cost, good biocompatibility and facile surface
      functionalizability. Our previous study, in which we used nanoparticles obtained
      by different methods showed the significance of size and way of production of
      nanodiamonds in their cellular effects. The aim of this study was to check the
      ability of surface-modified detonation nanodiamonds to reach intracellular
      compartments without degradation of the surface-conjugated drug or fluorescent
      marker. In this study we examined the penetration HUVEC-ST and A549 cells by
      detonation nanodiamonds (grain size <20 nm) modified by adding to, employing four
      pharmacological inhibitors of endocytosis, using optical, confocal and
      transmission electron microscopy We discuss the possibilities, the challenges of
      studying the endocytic pathways involved in cellular uptake of nanoparticles. Our
      results suggest that fluorescent nanomaterials are very promising for monitoring
      the intracellular fate of nanodiamonds.

PMID- 24882085
TI  - The Group Objective Structured Clinical Experience: building communication skills
      in the clinical reasoning context.
AB  - OBJECTIVE: Students are rarely taught communication skills in the context of
      clinical reasoning training. The purpose of this project was to combine the
      teaching of communication skills using SPs with clinical reasoning exercises in a
      Group Objective Structured Clinical Experience (GOSCE) to study feasibility of
      the approach, the effect on learners' self-efficacy and attitude toward learning
      communication skills, and the effect of providing multiple sources of immediate,
      collaborative feedback. METHODS: GOSCE sessions were piloted in Pediatrics and
      Medicine clerkships with students assessing their own performance and receiving
      formative feedback on communication skills from peers, standardized patients
      (SPs), and faculty. The sessions were evaluated using a retrospective pre/post
      training questionnaire rating changes in self-efficacy and attitudes, and the
      value of the feedback. RESULTS: Results indicate a positive impact on attitudes
      toward learning communication skills and self-efficacy regarding communication in
      the clinical setting. Also, learners considered feedback by peers, SPs, and
      faculty valuable in each GOSCE. CONCLUSION: The GOSCE is an efficient and learner
      centered method to attend to multiple goals of teaching communication skills,
      clinical reasoning, self-assessment, and giving feedback in a formative setting.
      PRACTICE IMPLICATIONS: The GOSCE is a low-resource, feasible strategy for
      experiential learning in communication skills and clinical reasoning.

PMID- 24882087
TI  - Talking about depression: an analogue study of physician gender and communication
      style on patient disclosures.
AB  - OBJECTIVES: To disentangle the effects of physician gender and patient-centered
      communication style on patients' oral engagement in depression care. METHODS:
      Physician gender, physician race and communication style (high patient-centered
      (HPC) and low patient-centered (LPC)) were manipulated and presented as
      videotaped actors within a computer simulated medical visit to assess effects on
      analogue patient (AP) verbal responsiveness and care ratings. 307 APs (56%
      female; 70% African American) were randomly assigned to conditions and instructed
      to verbally respond to depression-related questions and indicate willingness to
      continue care. Disclosures were coded using Roter Interaction Analysis System
      (RIAS). RESULTS: Both male and female APs talked more overall and conveyed more
      psychosocial and emotional talk to HPC gender discordant doctors (all p<.05). APs
      were more willing to continue treatment with gender-discordant HPC physicians
      (p<.05). No effects were evident in the LPC condition. CONCLUSIONS: Findings
      highlight a role for physician gender when considering active patient engagement
      in patient-centered depression care. This pattern suggests that there may be
      largely under-appreciated and consequential effects associated with patient
      expectations in regard to physician gender that these differ by patient gender.
      PRACTICE IMPLICATIONS: High patient-centeredness increases active patient
      engagement in depression care especially in gender discordant dyads.

PMID- 24882089
TI  - A versatile electrochemical sensing receptor based on a molecularly imprinted
      polymer.
AB  - Electrochemical molecularly imprinted polymers (e-MIPs) are reported for the
      first time. Their elaboration is based on the introduction of a redox tracer
      (vinylferrocene) inside the binding cavities of a cross-linked MIP. Determination
      of the analyte (benzo[a]pyrene) can be simply performed by measuring the redox
      tracer signal. 

PMID- 24882086
TI  - Provider interaction with the electronic health record: the effects on patient
      centered communication in medical encounters.
AB  - OBJECTIVE: The computer with the electronic health record (EHR) is an additional
      'interactant' in the medical consultation, as clinicians must simultaneously or
      in alternation engage patient and computer to provide medical care. Few studies
      have examined how clinicians' EHR workflow (e.g., gaze, keyboard activity, and
      silence) influences the quality of their communication, the patient's involvement
      in the encounter, and conversational control of the visit. METHODS: Twenty-three
      primary care providers (PCPs) from USA Veterans Administration (VA) primary care
      clinics participated in the study. Up to 6 patients per PCP were recruited. The
      proportion of time PCPs spent gazing at the computer was captured in real time
      via video-recording. Mouse click/scrolling activity was captured through Morae, a
      usability software that logs mouse clicks and scrolling activity. Conversational
      silence was coded as the proportion of time in the visit when PCP and patient
      were not talking. After the visit, patients completed patient satisfaction
      measures. Trained coders independently viewed videos of the interactions and
      rated the degree to which PCPs were patient-centered (informative, supportive,
      partnering) and patients were involved in the consultation. Conversational
      control was measured as the proportion of time the PCP held the floor compared to
      the patient. RESULTS: The final sample included 125 consultations. PCPs who spent
      more time in the consultation gazing at the computer and whose visits had more
      conversational silence were rated lower in patient-centeredness. PCPs controlled
      more of the talk time in the visits that also had longer periods of mutual
      silence. CONCLUSIONS: PCPs were rated as having less effective communication when
      they spent more time looking at the computer and when there was more periods of
      silence in the consultation. Because PCPs increasingly are using the EHR in their
      consultations, more research is needed to determine effective ways that they can
      verbally engage patients while simultaneously managing data in the EHR. PRACTICE
      IMPLICATIONS: EHR activity consumes an increasing proportion of clinicians' time
      during consultations. To ensure effective communication with their patients,
      clinicians may benefit from using communication strategies that maintain the flow
      of conversation when working with the computer, as well as from learning EHR
      management skills that prevent extended periods of gaze at computer and long
      periods of silence. Next-generation EHR design must address better usability and
      clinical workflow integration, including facilitating patient-clinician
      communication.

PMID- 24882090
TI  - Fascia lata onlay patch for repairing infected incisional hernias.
AB  - Abdominal incisional hernias represent the most common wound complication after
      abdominal surgery and infected abdominal incisional hernias are difficult to
      manage. We describe a simple, safe and effective method of using a free fascia
      lata patch to repair a large infected incisional hernia. This procedure involves
      the following steps: incising the skin and subcutaneous tissue and identifying
      the edges of the hernia defect; incising each anterior rectus sheath and
      completely suturing the medial edges of the fascia with 0 polypropylene; creating
      a fascia lata patch; and overlapping the defect in the anterior rectus fascia
      with the fascia lata patch as an onlay graft to reinforce the fascial closure.
      Five patients with infected hernias underwent this procedure, and all
      postoperative outcomes were satisfactory. 

PMID- 24882091
TI  - Management of traumatic aortic rupture (Watanabe et al. Surg Today. 2013;43:1339
      46).

PMID- 24882088
TI  - Low literacy is associated with uncontrolled blood pressure in primary care
      patients with hypertension and heart disease.
AB  - OBJECTIVES: To evaluate the association between low literacy and uncontrolled
      blood pressure (BP) and their associations with medication adherence. METHODS:
      Cross-sectional study of 423 urban, primary care patients with hypertension and
      coronary disease. The relationship between low literacy (Rapid Estimate of Adult
      Literacy in Medicine <= 44) and uncontrolled BP (>=140/90 mmHg, >=130/80 mmHg for
      patients with diabetes) was evaluated by crude and adjusted logistic regression.
      Relationships with self-reported adherence and refill adherence were explored
      using adjusted linear and logistic regression. RESULTS: Overall, 192 (45%)
      subjects had low literacy and 227 (52.9%) had uncontrolled BP. Adjusting for age,
      gender, race, employment, education, mental status, and self-reported adherence,
      low literacy was associated with uncontrolled BP (OR 1.75, 95% CI 1.06-2.87).
      Lower self-reported adherence was associated with uncontrolled BP; the
      relationship between refill adherence and uncontrolled BP was not statistically
      significant. CONCLUSION: Low literacy is independently associated with
      uncontrolled BP. PRACTICE IMPLICATIONS: Awareness of the relationships among
      patient literacy, BP control, and medication adherence may guide healthcare
      providers as they communicate with patients.

PMID- 24882093
TI  - Do males bite females' antennae to coerce copulation or to continue mate guarding
      in Oiceoptoma subrufum (Coleoptera: Silphinae)?
AB  - In several species, males frequently immobilize females during copulation. In
      some species, female immobilization enables males to copulate with unwilling
      females, while in others, female immobilization prolongs postcopulatory guarding.
      Male carrion beetles often bite and pull hard on one of the female's antennae
      during copulatory mounting. Previous descriptive studies have hypothesized that
      antenna biting is important for postcopulatory guarding in Silphinae. Here, we
      observed the mating behavior of Oiceoptoma subrufum, to understand the roles of
      antenna-biting in the initiation and termination of copulation. We compared the
      success and duration of intromission and pre- and postcopulatory mounting
      duration between males that did and did not bite female antennae during
      copulatory mounting. The success and duration of intromission and precopulatory
      mounting duration were unaffected by antenna biting. However, antenna-biting
      males mounted females for longer after intromission compared to non-biting males.
      These results indicate that antenna biting contributes to postcopulatory guarding
      behavior, not coercive copulation, in O. subrufum. 

PMID- 24882092
TI  - The broken ring: reduced aromaticity in Lys-Trp cations and high pH tautomer
      correlates with lower quantum yield and shorter lifetimes.
AB  - Several nonradiative processes compete with tryptophan fluorescence emission. The
      difficulty in spectral interpretation lies in associating specific molecular
      environmental features with these processes and thereby utilizing the
      fluorescence spectral data to identify the local environment of tryptophan. Here,
      spectroscopic and molecular modeling study of Lys-Trp dipeptide charged species
      shows that backbone-ring interactions are undistinguished. Instead, quantum
      mechanical ground state isosurfaces reveal variations in indole pi electron
      distribution and density that parallel charge (as a function of pK(1), pK(2), and
      pK(R)) on the backbone and residues. A pattern of aromaticity-associated quantum
      yield and fluorescence lifetime changes emerges. Where quantum yield is high,
      isosurfaces have a charge distribution similar to the highest occupied molecular
      orbital (HOMO) of indole, which is the dominant fluorescent ground state of the
      (1)L(a) transition dipole moment. Where quantum yield is low, isosurface charge
      distribution over the ring is uneven, diminished, and even found off ring. At pH
      13, the indole amine is deprotonated, and Lys-Trp quantum yield is extremely low
      due to tautomer structure that concentrates charge on the indole amine; the
      isosurface charge distribution bears scant resemblance to the indole HOMO. Such
      greatly diminished fluorescence has been observed for proteins where the indole
      nitrogen is hydrogen bonded, lending credence to the association of aromaticity
      changes with diminished quantum yield in proteins as well. Thus tryptophan ground
      state isosurfaces are an indicator of indole aromaticity, signaling the partition
      of excitation energy between radiative and nonradiative processes.

PMID- 24882095
TI  - Identification of neurotensin and LANT-6 and localization of mRNA encoding their
      precursor in the chicken brain.
AB  - Neurotensin (NT) and neurotensin-related peptide (Lys(8), Asn(9), NT(8-13): LANT
      6) have previously been purified from chicken intestine. However, the presence of
      these peptides and the localization of their precursor mRNA in the brain were not
      well understood. In the present study, through a comprehensive analysis of
      bioactive substances, NT and LANT-6 were identified in the chicken brain using
      tandem mass spectrometry combined with a bioassay of the colon contraction. The
      effect of NT and LANT-6 on the colon contraction was assessed, and NT was found
      to be 10 times more potent than LANT-6. Furthermore, the sites of NT/LANT-6
      precursor mRNA expression in the brain were investigated using quantitative RT
      PCR. The result showed that the mRNA was expressed most in the telencephalon,
      followed by the diencephalon. In situ hybridization analysis revealed that cells
      containing NT/LANT-6 precursor mRNA were widely distributed throughout the brain
      except for the cerebellum. Additionally, these were highly concentrated in the
      frontal telencephalon, including the nidopallium, hyperpallium, and hippocampus.
      Collectively, these results indicate that NT and LANT-6 are produced in the
      chicken brain, and they may participate in multiple functions. 

PMID- 24882094
TI  - Sex-specific parental care strategies via nestling age: females pay more
      attention to nestling demands than males do in the horned lark, Eremophila
      alpestris.
AB  - In many species, nestling demands vary continuously during early development and
      both parents have different parental care strategies at each nestling age. Sexual
      conflict arises when each parent expects its partner investing more in parental
      care. It is largely unknown how the two parents respond to the dynamics of
      nestling demands and resolve the sexual conflict during nestling period,
      especially on Qinghai-Tibetan Plateau. To address this question, we monitored
      parental care behaviors of horned larks (Eremophila alpestris) using video
      recording systems. We found that male horned larks invested less in parental
      care, but had a larger body size than females, which is consistent with the
      parental investment hypothesis. Only the female brooded nestlings, but both
      parents contributed to feeding efforts. Feeding rates of males and females were
      negatively correlated, indicating that they used evolutionarily stable
      strategies. Strategies of parental care via nestling age were sex-specific.
      Females continuously adjusted care behaviors to follow the dynamics of nestling
      demands as nestling age increased, such as decreasing brood attentiveness and
      increasing feeding rate. By contrast, male feeding rate showed no significant
      correlation with nestling age, but increased with the synchrony feeding rate. We
      suggest the synchrony feeding behavior may act as a control measure for females
      to promote and assess the males' contribution. We consider low mating
      opportunities drive males to act as assistants for females, and correspondingly
      cause males to pay less attention to nestling demands than females. 

PMID- 24882097
TI  - Symmetrical reproductive compatibility of two species in the Ciona intestinalis
      (Ascidiacea) species complex, a model for marine genomics and developmental
      biology.
AB  - The sea squirt Ciona intestinalis species complex is a widely used model system
      for genomics and developmental biology, as well as ecology. Contrary to previous
      reports, here we show no difference in the success of development and hatching
      between hybrid and conspecific crosses between the two species within this
      complex known as types A and B, from a region in the English Channel where they
      are sympatric. We grew laboratory hybrids in the field for three months, and
      successfully obtained reproductive adults. In back-crosses of F1 laboratory
      hybrids to parental types, normal larvae were obtained. We conclude that hybrid
      crosses generate viable offspring and the resulting hybrids are interfertile with
      types A and B. However we also show that introgression in the natural sympatric
      population remains low. We discuss possible pre-zygotic and post-zygotic
      mechanisms which reproductively isolate these species. 

PMID- 24882096
TI  - Transfer and detection of freshly isolated or cultured chicken (Gallus gallus)
      and exotic species' embryonic gonadal germ stem cells in host embryos.
AB  - The management of captive avian breeding programs increasingly utilizes various
      artificial reproductive technologies, including in ovo sexing of embryos to
      adjust population sex ratios. Currently, however, no attention has been given to
      the loss of genetic diversity following sex-selective incubation, even with
      respect to individuals from critically endangered species. This project evaluated
      the possibility of using xenotransfer of embryonic gonadal germline stem cells
      (GGCs) for future reintroduction of their germplasm into the gene pool. We
      examined and compared the host gonad colonization of freshly isolated and 3 day
      (3d) cultured donor GGCs from chicken and 13 species of exotic embryos. Following
      3d-culture of GGCs, there was a significant increase in the percentage of stem
      cell marker (SSEA-1, -3, -4) positive cells. However, the percentage of positive
      host gonads with chicken donor-derived cells decreased from 68% (fresh) to 22%
      (3d), while the percentage of exotic species donor-cells positive host gonads
      decreased from 61% (fresh) to 49% (3d-cultured). Donor GGCs from both chicken and
      exotic species were localized within the caudal endoderm, including the region
      encompassing the gonadal ridge by 16 hours post-injection. Furthermore, donor
      derived cells isolated from stage 36 host embryos were antigenic for anti SSEA-1,
      VASA/DDX4 and EMA-1 antibodies, presumably indicating maintenance of stem cell
      identity. This study demonstrates that GGCs from multiple species can migrate to
      the gonadal region and maintain presumed stemness following xenotransfer into a
      chicken host embryo, suggesting that germline stem cell migration is highly
      conserved in birds. 

PMID- 24882098
TI  - Contrasting population histories of the deep-sea demersal fish, Lycodes
      matsubarai, in the Sea of Japan and the Sea of Okhotsk.
AB  - Recent studies have revealed the impact of the drastic climate change during the
      last glacial period on coastal marine and anadromous species in the marginal seas
      of the northwestern Pacific Ocean; however, its influence on deep-sea species
      remains poorly understood. To compare the effects of the last glacial period on
      populations from the Sea of Japan and the Sea of Okhotsk, we examined the
      mitochondrial control region and cytochrome b gene sequences of Lycodes
      matsubarai, a deepsea demersal fish that inhabits these two seas. Our results
      showed clear genetic differentiation of populations between the two seas. The
      populations may have diverged during the last glacial period, probably as a
      result of vicariance due to the drastic sea level change. The population in the
      Sea of Okhotsk was larger than that in the Sea of Japan, but suddenly decreased
      after the last glacial period. However, the Sea of Japan population expanded
      after the last glacial period, coincident with high levels of oxygenation in deep
      sea areas. These results elucidate regional-scale impacts of climate change on
      deep-sea organisms. 

PMID- 24882099
TI  - Comparisons of host specificity in feather louse genera (Insecta: Phthiraptera:
      Philopteridae) parasitizing gulls (Aves: Laridae: Larus).
AB  - Data from gene sequences and morphological structures were collected for the gull
      feather lice, Saemundssonia lari, Quadraceps punctatus, and Q. ornatus,
      parasitizing Larus crassirostris and L. schistisagus. Saemundssonia lari was
      collected from both gull species, and no detectable morphological and genetic
      differences were found between lice collected from the two different hosts. In
      contrast, Q. punctatus was only collected from L. crassirostris, whereas Q.
      ornatus was only collected from L. schistisagus. The two Quadraceps species were
      genetically highly divergent, and body-size differences corresponding to the
      gull's body size (Harrison's rule) were also detected between them. Both
      Quadraceps species were collected from the interbarb of the remex or rectrix, and
      a match in body size between the louse and the interbarb space may be important
      in escape from host preening defenses. In contrast, Saemundssonia is a head
      louse, inhabiting the finer feathers of the head and neck, which the bird cannot
      preen. A close match to host body size may be less important for lice in the head
      microhabitat. The differences in the pattern of host-specificity between
      Saemundssonia and Quadraceps on the two focal host species of this study were
      probably due to their different microhabitat preferences. More broadly,
      comparisons of the gene sequences of S. lari and Q. punctatus to those from other
      gull hosts showed that genetically almost undifferentiated populations of both
      species were distributed on wide range of gull species. Frequent interspecific
      hybridization of gulls is one possible factor that may allow these lice to
      maintain gene flow across multiple host species. 

PMID- 24882100
TI  - Macrophage colony-stimulating factor induces prolactin expression in rat
      pituitary gland.
AB  - We investigated the role of macrophage colony-stimulating factor (M-CSF) in the
      pituitary gland to understand the effect of M-CSF on pituitary hormones and the
      relationship between the endocrine and immune systems. When we attempted to
      establish pituitary cell lines from a thyrotropic pituitary tumor (TtT), a
      macrophage cell line, TtT/M-87, was established. We evaluated M-CSF-like activity
      in conditioned media (CM) from seven pituitary cell lines using TtT/M-87 cells.
      TtT/M-87 proliferation significantly increased in the presence of CM from TtT/GF
      cells, a pituitary folliculostellate (FS) cell line. M-CSF mRNA was detected in
      TtT/GF and MtT/E cells by reverse transcriptase-polymerase chain reaction (RT
      PCR), and its expression in TtT/GF cells was increased in a lipopolysaccharide
      (LPS) dose-dependent manner. M-CSF mRNA expression was also increased in rat
      anterior pituitary glands by LPS. M-CSF receptor (M-CSFR) mRNA was only detected
      in TtT/ M-87 cells and increased in the LPS-stimulated rat pituitary glands. In
      rat pituitary glands, M-CSF and M-CSFR were found to be localized in FS cells and
      prolactin (PRL)-secreting cells, respectively, by immunohistochemistry. The PRL
      concentration in rat sera was significantly increased at 24 h after M-CSF
      administration, and mRNA levels significantly increased in primary culture cells
      of rat anterior pituitary glands. In addition, TNF-alpha mRNA was increased in
      the primary culture cells by M-CSF. These results revealed that M-CSF was
      secreted from FS cells and M-CSF regulated PRL expression in rat pituitary
      glands. 

PMID- 24882101
TI  - Gonadal development and gonadotropin gene expression during puberty in cultured
      chub mackerel (Scomber japonicus).
AB  - Understanding puberty is important for establishing aquaculture in fish. In this
      study, we analyzed the timing and completion of pubertal development along with
      changes in pituitary gonadotropin genes (fshb and lhb) in cultured chub mackerel
      (Scomber japonicus). At 45 days post-hatching (dph), gonadal sex differentiation
      was observed. The onset of puberty occurred at 192 dph in females with the start
      of vitellogenesis, whereas it occurred at 164 dph in males, with the beginning of
      spermatogenesis (proliferation and differentiation of germ cells). The completion
      of puberty was at 326 dph in females when vitellogenesis completed, and it was at
      338 dph in males during spermiation. All fish sampled during the spawning season
      completed pubertal development. In the pituitary of female fish, fshb expression
      was activated during early secondary growth and was maintained high throughout
      vitellogenesis, whereas lhb expression was highest at the completion of
      vitellogenesis. In male fish, fshb and lhb expression were activated from the
      onset of spermatogenesis and further activated during late pubertal development;
      fshb remained high between late spermatogenesis and spermiation, whereas lhb was
      highest during spermiation. 

PMID- 24882102
TI  - Initial excited-state structural dynamics of 5,6-dimethyluracil from resonance
      Raman spectroscopy.
AB  - In order to understand the effect of methyl substitution patterns on the initial
      excited-state structural dynamics of uracil derivatives, we measured the
      resonance Raman spectra of 5,6-dimethyluracil (5,6-DMU). The results show that
      the resonance Raman spectrum is a combination of that of 5-methyl- and 6
      methyluracil. The resonance Raman excitation profiles (RREPs) and absorption
      spectrum are simulated with a self-consistent, time-dependent formalism to yield
      the excited-state slopes and broadening parameters. The initial excited-state
      structural dynamics occur primarily along the C5?C6 stretching mode, as expected,
      but with lesser excited-state slopes along each mode compared to 5-methyluracil
      and 6-methyluracil. This study along with previous experiments with different
      uracil derivatives show that the presence and positions of the methyl groups
      seems to determine the partitioning of initial excited-state structural dynamics.

PMID- 24882103
TI  - Size does matter--age-related weight estimation in "tall n' thin" and "tiny n'
      thick" children and a new habitus-adapted alternative to the EPLS-formula.
AB  - AIM OF THE STUDY: Weight in kilograms is a required parameter in the emergency
      medical care of children. In emergent situations, obtaining an accurate weight is
      often not possible. In such situations, weight can be estimated by using an age
      dependent formula such as the EPLS-formula (age in years+4)*2. As recently
      recognized for emergency tapes, the habitus of the child has a major influence on
      weight estimation. In this study, the performance of various age-dependent
      formulas is to be investigated, with special regard to children demonstrating non
      normal growth. METHODS: The performance of various formulas for weight estimation
      in children growing along the 5th, 50th, and 95th percentile is investigated
      based on a mathematical model compared to the WHO and CDC reference percentiles
      using ICC and Bland-Altman methods. Additionally, a new formula for children
      demonstrating non-normal growth is derived by regression analysis and tested:
      f*age in years+6 with the factor f being 2 for "tall n' thin", 3 for normal and 4
      for "tiny n' thick" children. RESULTS: All previously published formulas lack
      precision when applied to children outside the 50th percentile. The new habitus
      adapted formula shows a better performance for children growing along the 5th or
      95th percentile. CONCLUSIONS: The new formula provides enhanced precision in
      weight estimation and can help in reducing, e.g. drug dosing errors. It should be
      used for weight estimation in children demonstrating non-normal weight
      development and in situations when superior methods such as weighing or habitus
      adapted emergency tapes are not applicable.

PMID- 24882104
TI  - "Nobody is dead until warm and dead": prolonged resuscitation is warranted in
      arrested hypothermic victims also in remote areas--a retrospective study from
      northern Norway.
AB  - Hypothermic cardiac arrest has high mortality and few known prognostic factors.
      We studied retrospectively 34 victims of accidental hypothermia with cardiac
      arrest admitted to The University Hospital of North Norway during 1985-2013 who
      were resuscitated and rewarmed by extracorporeal circulation. No patient survived
      prior to 1999, while nine out of 24 (37.5%) survived hypothermic cardiac arrest
      from 1999 to 2013. The lowest measured core temperature among survivors was 13.7
      degrees C; the longest time from cardiac arrest to return of spontaneous
      circulation was 6 h and 52 min. The only predictor of survival identified was
      lower blood potassium concentration in the nine survivors compared with the non
      survivors. Submersion was not associated with reduced survival. Non-survivors
      consumed modest hospital resources. Most survivors had a favourable neurological
      outcome.

PMID- 24882106
TI  - An investigation of heat shock protein 27 and P-glycoprotein mediated multi-drug
      resistance in breast cancer using liquid chromatography-tandem mass spectrometry
      based targeted proteomics.
AB  - One missing puzzle piece to study heat shock protein 27 (HSP27) in P-glycoprotein
      (P-gp) mediated multi-drug resistance (MDR) was the amount of HSP27 and the
      extent of its phosphorylation in the biological context. Liquid chromatography
      tandem mass spectrometry (LC/MS/MS)-based targeted proteomics allows researchers
      to monitor associated proteins and their modification simultaneously and
      quantitatively. In this study, a targeted proteomics assay was first developed
      and validated for the quantification of HSP27 and its phosphorylated forms. Using
      this assay, the level of HSP27 was determined in non-tumoral cells MCF-10A,
      parental drug-sensitive cancer cells MCF-7/WT and drug-resistant cancer cells MCF
      7/ADR. A decrease of HSP27 expression was observed in P-gp overexpressed MCF
      7/ADR cells. A quantitative time-course analysis of both HSP27 and P-gp in
      doxorubicin (DOX)-treated MCF-7/WT cells also implied that HSP27 may participate
      in the P-gp modulation. Furthermore, stoichiometry of site-specific HSP27
      phosphorylation indicated that DOX treatment rapidly induced the HSP27
      phosphorylation at Ser82. Moreover, conventional analytical methods were also
      performed for a comparison. BIOLOGICAL SIGNIFICANCE: LC/MS/MS-based targeted
      proteomics turns out to be a promising quantification approach for the study of
      proteins in the preclinical and clinical environment. Unfortunately, rare studies
      applied this technology to detect multiple associated proteins or protein
      modification in one experiment. This study demonstrated the potential of LC/MS/MS
      based targeted proteomics to understand the cell events in a more accurate
      context of biological system. By the quantitative time-course analysis of HSP27
      and its phosphorylated forms at sites of Ser15 and Ser82, the possible role of
      HSP27 in P-gp mediated MDR was suggested. Further development of targeted
      proteomics in future may provide more insight into signal transduction pathways
      upon perturbation of a protein network or changes to a panel of proposed
      biomarkers in a given disease state.

PMID- 24882105
TI  - Targeting class A and C serine beta-lactamases with a broad-spectrum boronic acid
      derivative.
AB  - Production of beta-lactamases (BLs) is the most widespread resistance mechanism
      adopted by bacteria to fight beta-lactam antibiotics. The substrate spectrum of
      BLs has become increasingly broad, posing a serious health problem. Thus, there
      is an urgent need for novel BL inhibitors. Boronic acid transition-state
      analogues are able to reverse the resistance conferred by class A and C BLs. We
      describe a boronic acid analogue possessing interesting and potent broad-spectrum
      activity vs class A and C serine-based BLs. Starting from benzo(b)thiophene-2
      boronic acid (BZBTH2B), a nanomolar non-beta-lactam inhibitor of AmpC that can
      potentiate the activity of a third-generation cephalosporin against AmpC
      producing resistant bacteria, we designed a novel broad-spectrum nanomolar
      inhibitor of class A and C BLs. Structure-based drug design (SBDD), synthesis,
      enzymology data, and X-ray crystallography results are discussed. We clarified
      the inhibitor binding geometry responsible for broad-spectrum activity vs serine
      active BLs using double mutant thermodynamic cycle studies. 

PMID- 24882107
TI  - Living with osteoarthritis: a systematic review and meta-ethnography.
AB  - OBJECTIVES: To review and synthesize the existing literature on the experience of
      living with a diagnosis of hip and/or knee osteoarthritis (OA). METHOD: A
      systematic review was undertaken using meta-ethnography. A search of both
      published (AMED, CINAHL, EMBASE, PsychINFO, SportsDisc, MEDLINE, Cochrane
      Clinical Trials Registry, PubMed) and unpublished/trial registry databases [World
      Health Organization (WHO) International Clinical Trials Registry Platform,
      Current Controlled Trials, the United States National Institute of Health Trials
      Registry, National Institute for Health Research (NIHR) Clinical Research
      Portfolio Database] was undertaken from their inception to 5 June 2013. RESULTS:
      Thirty-two studies formed the meta-ethnography of the lived experiences of people
      with OA. In total, 1643 people with OA were sampled, the majority diagnosed with
      knee OA. The evidence base was weak to moderate in quality. The majority of
      studies indicated that people viewed living with OA negatively. Four key factors
      influenced their attitudes to the condition: the severity of their symptoms; the
      impact of these symptoms on their functional capability; their attitude towards
      understanding their disease; and their perceptions of other people's beliefs
      towards their disease. CONCLUSIONS: The current literature suggests that greater
      knowledge of the pathology of OA, management of symptoms, promotion of functional
      activity for patients and their family/friends networks, and understanding to
      better inform OA patient's role in society are all important elements that affect
      a person's attitude to OA. By better understanding these factors during future
      consultations, clinicians may forge stronger relationships with their patients to
      more effectively manage this long-term disabling condition.

PMID- 24882108
TI  - In vitro osteoinduction of human mesenchymal stem cells in biomimetic surface
      modified titanium alloy implants.
AB  - Interaction between cells and implant surface is crucial for clinical success.
      This interaction and the associated surface treatment are essential for achieving
      a fast osseointegration process. Several studies of different topographical or
      chemical surface modifications have been proposed previously in literature. The
      Biomimetic Advanced Surface (BAS) topography is a combination of a shot blasting
      and anodizing procedure. Macroroughness, microporosity of titanium oxide and
      Calcium/Phosphate ion deposition is obtained. Human mesenchymal stem cells
      (hMCSs) response in vitro to this treatment has been evaluated. The results
      obtained show an improved adhesion capacity and a higher proliferation rate when
      hMSCs are cultured on treated surfaces. This biomimetic modification of the
      titanium surface induces the expression of osteblastic differentiation markers
      (RUNX2 and Osteopontin) in the absence of any externally provided differentiation
      factor. As a main conclusion, our biomimetic surface modification could lead to a
      substantial improvement in osteoinduction in titanium alloy implants. 

PMID- 24882109
TI  - Effects of simulated gastric juice on color stability, surface roughness and
      microhardness of laboratory-processed composites.
AB  - Medical problems such as gastroesophageal reflux disease can cause considerable
      damage to restorations in the oral environment. This study evaluated the effects
      of gastric juice on the surface characteristics of different types of laboratory
      processed indirect composites with different filler particles and polymerization
      modes. Specimens were prepared from Tescera (TES; Bisco), Sinfony (SIN; 3M ESPE),
      Solidex (SOL; Shofu), and Adoro (AD; Ivoclar Vivadent). Before exposing the
      specimens to simulated gastric juice for 24 h, color, surface roughness, and
      microhardness were measured on one half of the polished flat surface of each
      specimen. After exposure to the simulated gastric juice, the same tests were
      repeated on the other half of specimen surface. Results indicated that gastric
      juice had a significant impact on color change (p<0.001). AD showed the largest
      surface roughness change among the resins (p<0.001). Gastric juice also
      significantly affected the microhardness of the materials, and AD and TES showed
      statistically similar change in microhardness (p>0.05). 

PMID- 24882110
TI  - Comparative evaluation of various miniplate systems for the repair of mandibular
      corpus fractures.
AB  - Miniplates have been used during the last decade to facilitate stability between
      bony fragments in the maxillofacial region and are currently the preferred
      surgical method for the fixation of fractures and osteotomies. The aim of this
      study was to evaluate and compare the biomechanical behaviors of six different
      types of miniplates used to reconstruct mandibular body fractures: Group 1
      (straight, 2 holes, 12.0 mm spacing), Group 2 (straight, 4 holes, 9.0 spacing),
      Group 3 (straight, 6 holes, 9.0 mm spacing), Group 4 (L-shaped, 4 holes, 9.0 mm
      spacing, right hand plate), Group 5 (Y-shaped, 5 holes, 12.0 mm spacing), and
      Group 6 (double Y-shaped, 6 holes, 9.0 mm spacing). Thirty bovine hemimandibles
      and a custom-made 3-point biomechanical test frame mounted on a Shimadzu
      universal test machine were used to evaluate the six different miniplate systems.
      Results revealed that Group 1 (straight, 2 holes, 12.0 mm spacing) and Group 4
      (9.0 mm spacing, right hand plate) had the lowest biomechanical stability,
      whereas Group 6 (6 holes, 9.0 mm spacing) had the highest biomechanical
      stability. Group 6 also provided statistically greater resistance to displacement
      than Group 1 and Group 4. 

PMID- 24882111
TI  - Effect of calcium salt of 10-methacryloyloxydecyl dihydrogen phosphate produced
      on the bond durability of one-step self-etch adhesive.
AB  - Five experimental 10-methacryloyloxydecyl dihydrogen phosphate (MDP)-based one
      step self-etch adhesives were designed by varying amounts of MDP. The aim of this
      study was to examine the effect of the quantity of calcium salt of MDP (MDP-Ca)
      salt produced by demineralization on the bond durability between experimental one
      step adhesives and enamel or dentin. Bond strengths of experimental adhesives to
      the enamel and dentin were measured, before and after 30,000*thermocycling. The
      fractured enamel and dentin samples as well as the fractured adhesive surfaces
      obtained during adhesion test were analyzed by a scanning electron microscope and
      energy-dispersive X-ray microscope. An increase in the amount of MDP-Ca salt to
      above 37.2 mg/g drastically decreased the dentin bond strength and changed the
      fracture type during the thermocycling process. In contrast, the enamel bond
      strength remained unchanged, although the fracture type changed to an interfacial
      failure with increasing the amount of MDP-Ca salt to 78.3 mg/g. 

PMID- 24882112
TI  - An analysis of the biofilms adhered to framework alloys using in vitro denture
      plaque models.
AB  - The purpose of this study was to perform a quantitative and qualitative
      evaluation of the biofilms formed on framework alloys in vitro. The biofilms
      formed by unfiltered fresh human saliva or Streptococcus mutans and/or Candida
      albicans on commercially pure titanium and gold-copper-platinum demonstrated
      higher amounts than other alloy and resin samples. In contrast, the
      silverpalladium-copper-gold showed a significantly decreased level of biofilm
      formation. Although the adhesion level of Streptococcus mutans on cobalt-chromium
      was high, that of Candida albicans was less extensive. A T-RFLP analysis and
      qualitative PCR of the microbes in the biofilms were performed. In a cluster
      analysis of all T-RFLP profiles, the cobalt-chromium pattern was integrated into
      one cluster. On qualitative PCR, the existence of microorganisms related to
      caries, preriodontitis and aspiration pneumonia was observed. Our results showed
      that the biofilm formation on each framework alloy was different in terms of both
      the quantity and quality. 

PMID- 24882113
TI  - Effects of immersion in solution of an experimental toothpaste containing S-PRG
      filler on like-remineralizing ability of etched enamel.
AB  - This study investigated the like-remineralizing ability of experimental
      toothpaste containing surface reaction-type pre-reacted glassionomer (S-PRG)
      filler on etched enamel. Human enamel blocks were etched with 35% phosphoric acid
      and immersed in 5-mL distilled water, fourfold diluted solution of NaF-containing
      toothpaste, or S-PRG filler-containing experimental toothpaste. Nanoindentation
      testing was carried out during immersion and the enamel surfaces were observed by
      scanning electron microscopy. Elemental analysis of the ions in each solution was
      performed using inductively coupled plasma atomic emission spectroscopy and
      fluoride electrode. After 1 month of immersion, the hardness and elastic modulus
      of the specimen immersed in S-PRG filler-containing toothpaste showed
      significantly greater values than those of the specimen immersed in NaF
      containing toothpaste. Considerable amounts of Al, B, Na, Si, Sr, F ions were
      detected in the solution of S-PRG filler-containing toothpaste. Experimental S
      PRG filler-containing toothpaste may enhance the like-remineralizing ability of
      etched enamel surfaces due to its ion-releasing ability. 

PMID- 24882114
TI  - A review of powered-two-wheeler behaviour and safety.
AB  - Powered-two-wheelers (PTWs) constitute a very vulnerable type of road users. The
      notable increase in their share in traffic and the high risk of severe accident
      occurrence raise the need for further research. However, current research on PTW
      safety is not as extensive as for other road users (passenger cars, etc.).
      Consequently, the objective of this research is to provide a critical review of
      research on Power-Two-Wheeler behaviour and safety with regard to data
      collection, methods of analysis and contributory factors, and discuss the needs
      for further research. Both macroscopic analyses (accident frequency, accident
      rates and severity) and microscopic analyses (PTW rider behaviour, interaction
      with other motorised traffic) are examined and discussed in this paper. The
      research gaps and the needs for future research are identified, discussed and put
      in a broad framework. When the interactions between behaviour, accident
      frequency/rates and severity are co-considered and co-investigated with the
      various contributory factors (riders, other users, road and traffic environment,
      vehicles), the accident and injury causes as well as the related solutions are
      better identified.

PMID- 24882115
TI  - Patient-centred interprofessional collaboration in primary care: challenges for
      clinical, educational and health services research. An EGPRN keynote paper.
AB  - The theme 'patient-centred interprofessional collaboration' of the EGPRN
      conference in October 2012, captures in just three words important challenges for
      European primary care and its research agenda. Challenges for future research are
      formulated, in three domains: clinical, educational and health services research.
      Transferability of research, based upon advanced computational infrastructure,
      will facilitate a rapid learning health care system. In educational research,
      this includes the use of observational and reflexivity methods. Outcomes should
      be defined in terms of improvement of functional status and social participation
      rather than in terms of disease-specific outcomes. Partnership with all
      stakeholders, patients, GPs and their health care colleagues and students, can
      help in reducing avoidable waste in the production and reporting of research
      evidence.

PMID- 24882117
TI  - Full-field dynamic characterization of superhydrophobic condensation on
      biotemplated nanostructured surfaces.
AB  - While superhydrophobic nanostructured surfaces have been shown to promote
      condensation heat transfer, the successful implementation of these coatings
      relies on the development of scalable manufacturing strategies as well as
      continued research into the fundamental physical mechanisms of enhancement. This
      work demonstrates the fabrication and characterization of superhydrophobic
      coatings using a simple scalable nanofabrication technique based on self-assembly
      of the Tobacco mosaic virus (TMV) combined with initiated chemical vapor
      deposition. TMV biotemplating is compatible with a wide range of surface
      materials and applicable over large areas and complex geometries without the use
      of any power or heat. The virus-structured coatings fabricated here are
      macroscopically superhydrophobic (contact angle >170 degrees ) and have been
      characterized using environmental electron scanning microscopy showing sustained
      and robust coalescence-induced ejection of condensate droplets. Additionally,
      full-field dynamic characterization of these surfaces during condensation in the
      presence of noncondensable gases is reported. This technique uses optical
      microscopy combined with image processing algorithms to track the wetting and
      growth dynamics of 100s to 1000s of microscale condensate droplets
      simultaneously. Using this approach, over 3 million independent measurements of
      droplet size have been used to characterize global heat transfer performance as a
      function of nucleation site density, coalescence length, and the apparent wetted
      surface area during dynamic loading. Additionally, the history and behavior of
      individual nucleation sites, including coalescence events, has been
      characterized. This work elucidates the nature of superhydrophobic condensation
      and its enhancement, including the role of nucleation site density during
      transient operation. 

PMID- 24882120
TI  - Perioperative consideration of obstructive sleep apnea in ambulatory surgery.
AB  - The prevalence of obstructive sleep apnea (OSA) is increasing and a significant
      number of patients with OSA are undiagnosed. The suitability of ambulatory
      surgery in patients with OSA remains controversial, and the evidence regarding
      the safety of ambulatory surgery for patients with OSA is limited. Preoperative
      screening and careful selection of patients for ambulatory surgery is the most
      important step. Patients diagnosed and suspected of having OSA should be managed
      with a systematic algorithm to improve outcomes. 

PMID- 24882119
TI  - Perioperative evaluation and management of cardiac disease in the ambulatory
      surgery setting.
AB  - Preoperative cardiac evaluation focuses on risk assessment and reduction.
      Diagnostic testing and interventions are used only when the risk of adverse
      outcomes is high and intervention will lower the risk. The evaluation is
      performed in a stepwise fashion according to guidelines in the literature. 

PMID- 24882121
TI  - Management of diabetes medications for patients undergoing ambulatory surgery.
AB  - A stress-free actively managed perioperative experience is crucial to successful
      ambulatory surgery for diabetes patients. Practitioners who integrate diabetes
      treatment regimens into their perioperative management can facilitate a good
      outcome, smooth recovery, and rapid return to normal life. Hypoglycemia,
      hyperglycemia, and glucose variability must be avoided and patients should be
      maintained near their usual blood glucose. 

PMID- 24882122
TI  - Peripheral nerve blocks for ambulatory surgery.
AB  - Peripheral nerve blocks (PNBs) provide significant improvement in postoperative
      analgesia and quality of recovery for ambulatory surgery. Use of continuous PNB
      techniques extend these benefits beyond the limited duration of single-injection
      PNBs. The use of ultrasound guidance has significantly improved the overall
      success, efficiency, and has contributed to the increased use of PNBs in the
      ambulatory setting. More recently, the use of ultrasound guidance has been
      demonstrated to decrease the risk of local anesthetic systemic toxicity. This
      article provides a broad overview of the indications and clinically useful
      aspects of the most commonly used upper and lower extremity PNBs in the
      ambulatory setting. Emphasis is placed on approaches that can be used for single
      injection PNBs and continuous PNB techniques. 

PMID- 24882123
TI  - Neuraxial anesthesia for outpatients.
AB  - Neuraxial anesthesia for outpatient surgery can provide excellent anesthesia for
      certain patients. The short-acting local anesthetic 2-chloroprocaine has an
      appropriate length of action for short outpatient procedures with a very low risk
      of transient neurologic symptoms. Epidural anesthesia with short-acting agents
      can provide good outpatient anesthesia for procedures lasting 90 minutes or
      longer.

PMID- 24882124
TI  - Anesthesia for ambulatory diagnostic and therapeutic radiology procedures.
AB  - The radiology suite presents the anesthesia provider with a unique set of
      challenges such as ionizing radiation, intravascular contrast, magnetic fields,
      physical separation and barriers from the patient, so-called borrowed space, and
      the large range of procedures performed. Most of these procedures will continue
      to be performed without the presence of an anesthesia team but, because of the
      ever-increasing complexity of the procedures being performed and the increasing
      comorbidities of patients, the anesthesia provider will likely be called more
      often to provide care. A thorough understanding of these challenges is essential
      to providing a safe anesthetic in a difficult environment. 

PMID- 24882125
TI  - Ambulatory anesthesia for the cardiac catheterization and electrophysiology
      laboratories.
AB  - The cardiac catheterization laboratory (CCL) and electrophysiology laboratory
      (EPL) environments present unique clinical challenges. These challenges include
      unfamiliar work areas and staff, limited space with physical barriers separating
      the patient from the care provider, remote locations, and procedures with rare
      but potentially catastrophic clinical complications. Ambulatory anesthesiologists
      must familiarize themselves with these new surroundings and practice vigilant
      preoperative planning and continual communication with the proceduralist and
      team. In the future, the need for anesthesiologists in the CCL and EPL will
      continue to grow as procedures increase in complexity and duration. 

PMID- 24882127
TI  - Chronic pain: anesthesia for procedures.
AB  - Chronic pain is a symptom that patients fear significantly. To treat and
      alleviate pain, physicians perform various interventions for which patients often
      need to be immobile for long periods of time. To improve patient satisfaction and
      relief anxiety of those complex procedures, pain physicians use various
      anesthetic techniques for their pain-relieving procedures that range from local
      skin infiltration to general anesthesia with endotracheal intubation. This
      article describes the anesthetic techniques used in interventional pain
      procedures and their indications, side effects, and complications. 

PMID- 24882126
TI  - Nonoperating room anesthesia for the gastrointestinal endoscopy suite.
AB  - Anesthesia services are increasingly being requested for gastrointestinal (GI)
      endoscopy procedures. The preparation of the patients is different from the
      traditional operating room practice. The responsibility to optimize comorbid
      conditions is also unclear. The anesthetic techniques are unique to the
      procedures, as are the likely events that require intervention by the anesthesia
      team. The postprocedure care is also unique. The future needs for anesthesia
      services in GI endoscopy suite are likely to expand with further developments of
      the technology. 

PMID- 24882128
TI  - Pediatric ambulatory anesthesia.
AB  - Pediatric patients often undergo anesthesia for ambulatory procedures. This
      article discusses several common preoperative dilemmas, including whether to
      postpone anesthesia when a child has an upper respiratory infection, whether to
      test young women for pregnancy, which children require overnight admission for
      apnea monitoring, and the effectiveness of nonpharmacological techniques for
      reducing anxiety. Medication issues covered include the risks of anesthetic
      agents in children with undiagnosed weakness, the use of remifentanil for
      tracheal intubation, and perioperative dosing of rectal acetaminophen. The
      relative merits of caudal and dorsal penile nerve block for pain after
      circumcision are also discussed. 

PMID- 24882129
TI  - Initial results from the National Anesthesia Clinical Outcomes Registry and
      overview of office-based anesthesia.
AB  - Safe office-based anesthesia practices dictate proper patient and procedure
      selection, appropriate provider qualifications, adequately equipped facilities,
      and effective administrative infrastructure. Analysis of patient outcomes can
      help reduce mortality and morbidity by identifying high-risk patients and
      procedures. We analyzed data from the Anesthesia Quality Institute National
      Anesthesia Clinical Outcomes Registry. Analysis included patient demographics and
      outcomes, procedure and anesthesia type and duration, and case coverage by
      provider. Increased regulation and standardization of care, such as the use of
      checklists and professional guidelines, can advance safe practices. There is
      increasing emphasis on continuous quality improvement, electronic health records,
      and outcomes data reporting. 

PMID- 24882130
TI  - Airway management.
AB  - In this article, recent literature related to airway management in the ambulatory
      surgery setting is reviewed. Practical pointers to improve clinical success and
      avoid complications of newer airway management techniques are provided. 

PMID- 24882131
TI  - New medications and techniques in ambulatory anesthesia.
AB  - Novel anesthetic and analgesic agents are currently under development or
      investigation to improve anesthetic delivery and patient care. The
      pharmacokinetic and analgesic profiles of these agents are especially tailored to
      meet the challenges of rapid recovery and opioid minimization associated with
      ambulatory anesthesia practice. 

PMID- 24882132
TI  - Postoperative issues: discharge criteria.
AB  - With the continuous increase in the numbers and complexity of cases being done as
      ambulatory procedures, striking a balance between operational efficiency, patient
      safety, and patient satisfaction has become increasingly difficult. This article
      summarizes the latest evidence and consensus with regard to discharging an
      ambulatory patient home, the use of patient recovery scoring systems for protocol
      based decision making, the concept of fast-track recovery, and requirements for
      patient escort. Fast-tracking (ie, bypassing the postanesthesia care unit) is an
      acceptable and safe pathway, provided careful patient selection and assessment
      are performed. 

PMID- 24882133
TI  - Acute pain management.
AB  - This article updates acute pain management in ambulatory surgery and proposes a
      practical three-step approach for reducing the impact and incidence of
      uncontrolled surgical pain. By identifying at-risk patients, implementing
      multimodal analgesia, and intervening promptly with rescue therapies, the
      anesthesiologist may improve outcomes, reduce cost, and optimize the patient's
      experience and quality of recovery. 

PMID- 24882134
TI  - Long-acting serotonin antagonist (Palonosetron) and the NK-1 receptor
      antagonists: does extended duration of action improve efficacy?
AB  - In a growing outpatient surgical population, postdischarge nausea and vomiting
      (PDNV) is unfortunately a common and costly anesthetic complication.
      Identification of risk factors for both postoperative nausea and vomiting and
      PDNV is the hallmark of prevention and management. New pharmacologic
      interventions with extended duration of action, including palonosetron and
      aprepritant, may prove to be more efficacious. 

PMID- 24882135
TI  - Scheduling of procedures and staff in an ambulatory surgery center.
AB  - For ambulatory surgical centers (ASC) to succeed financially, it is critical for
      ASC managers to schedule surgical procedures in a manner that optimizes operating
      room (OR) efficiency. OR efficiency is maximized by using historical data to
      accurately predict future OR workload, thereby enabling OR time to be properly
      allocated to surgeons. Other strategies to maintain a well-functioning ASC
      include recruiting and retaining the right staff and ensuring patients and
      surgeons are satisfied with their experience. This article reviews different
      types of procedure scheduling systems. Characteristics of well-functioning ASCs
      are also discussed. 

PMID- 24882137
TI  - Legal aspects of ambulatory anesthesia.
AB  - This article informs anesthesiologists of some of the legal issues they may
      encounter in connection with ambulatory surgical center-based or office-based
      practice. The primary legal issues that anesthesiologists face in connection with
      practice in such settings can be broken down into practice-related issues and
      ownership-related issues. Given the complexity of legal issues relating to
      ambulatory anesthesia, anesthesiologists are advised to consult counsel at an
      early stage so as to understand the issues that may apply to their practices. 

PMID- 24882136
TI  - Practice management/role of the medical director.
AB  - Although the nature of ambulatory surgery has changed over the years, the ideal
      role of the medical director mirrors its earliest iterations, focusing on
      excellent customer service and high quality of care. These efforts are supported
      by 3 modern methods of quality management borrowed from industry: intentional
      process improvement, standard care pathways, and monitoring outcomes to determine
      the efficacy of each. These methods are critical to master in order to lead the
      facility and providers to the highest quality of care and service. 

PMID- 24882138
TI  - Accreditation of ambulatory facilities.
AB  - With the continued growth of ambulatory surgical centers (ASC), the regulation of
      facilities has evolved to include new standards and requirements on both state
      and federal levels. Accreditation allows for the assessment of clinical practice,
      improves accountability, and better ensures quality of care. In some states, ASC
      may choose to voluntarily apply for accreditation from a recognized organization,
      but in others it is mandated. Accreditation provides external validation of safe
      practices, benchmarking performance against other accredited facilities, and
      demonstrates to patients and payers the facility's commitment to continuous
      quality improvement. 

PMID- 24882139
TI  - Anesthesia information management systems in the ambulatory setting: benefits and
      challenges.
AB  - Adopting an anesthesia information management system (AIMS) is a challenge for
      anesthesia departments. The transition requires a physician champion and the
      support of members in every section. This change can be facilitated by visiting
      similar institutions that are already using AIMS, shadow charting for a
      sufficient period of time, and understanding that optimization continues after
      the go-live date. Once implemented, the benefits outweigh the challenges, but
      understanding where the potential obstacles lie is critical to removing them
      efficiently and effectively. As different AIMS continue to spread throughout the
      medical world, so will their benefits. 

PMID- 24882140
TI  - Quality management and registries.
AB  - This article provides a review of key concepts in quality management (QM) for
      ambulatory anesthesia. The importance of collecting data from every case is
      emphasized, and important outcome measures are recommended. The use of specific
      data collection tools and methodologies is discussed, including the national
      registry projects of the Society for Ambulatory Anesthesia and the Anesthesia
      Quality Institute. A brief overview is provided of how to use QM data to improve
      patient outcomes within an anesthesia practice. 

PMID- 24882141
TI  - Ambulatory anesthesia.

PMID- 24882142
TI  - The four Ps: place, procedure, personnel, and patient.

PMID- 24882143
TI  - Nicotine effects and the endogenous opioid system.
AB  - Nicotine (NIC) is an exogenous ligand of the nicotinic acetylcholine receptor
      (nAChR), and it influences various functions in the central nervous system.
      Systemic administration of NIC elicits the release of endogenous opioids
      (endorphins, enkephalins, and dynorphins) in the supraspinal cord. Additionally,
      systemic NIC administration induces the release of methionine-enkephalin in the
      spinal dorsal horn. NIC has acute neurophysiological actions, including
      antinociceptive effects, and the ability to activate the hypothalamic-pituitary
      adrenal (HPA) axis. The endogenous opioid system participates in NIC-induced
      antinociception, but not HPA axis activation. Moreover, NIC-induced
      antinociception is mediated by alpha4beta2 and alpha7 nAChRs, while NIC-induced
      HPA axis activation is mediated by alpha4beta2, not alpha7, suggesting that the
      effects of NIC on the endogenous opioid system are mediated by alpha7, not
      alpha4beta2. NIC has substantial physical dependence liability. The opioid
      receptor antagonist naloxone (NLX) elicits NIC withdrawal after repeated NIC
      administration, and NLX-induced NIC withdrawal is inhibited by concomitant
      administration of an opioid-receptor antagonist. NLX-induced NIC withdrawal is
      also inhibited by concomitant administration of an alpha7 antagonist, but not an
      alpha4beta2 antagonist. Taken together, these findings suggest that NIC-induced
      antinociception and the development of physical dependence are mediated by the
      endogenous opioid system, via the alpha7 nAChR. 

PMID- 24882145
TI  - Systems biology with omics data.

PMID- 24882144
TI  - Central coherence in eating disorders: an updated systematic review and meta
      analysis.
AB  - OBJECTIVES: A bias towards local information over the global "gist" (weak central
      coherence, WCC), has been identified as a possible contributing and maintaining
      factor in eating disorders (ED). The present study aimed to provide an updated
      review of the WCC literature and examine the hypothesis that individuals with ED
      have WCC. METHODS: The new search found 12 eligible studies. Meta-analyses were
      performed on nine of these 12 studies, the remaining three were commented on
      individually. Data were combined with data from the previous 2008 review, and
      meta- analyses were performed on 16 studies (nine studies from the new search and
      seven studies from 2008 review). RESULTS: Meta-analysis of the Group Embedded
      Figures Task provided evidence of superior local processing across all ED
      subtypes (pooled effect size of d = -0.62 (95% CI = -0.94, -0.31), P < 0.001).
      Evidence of poorer global processing in ED groups was found from meta-analyses of
      the Rey-Osterrieth Complex Figures task (d = -0.63 (95% CI = -0.77, -0.49, P <
      0.001), and the Object Assembly Task (d = -0.65 (95% CI = -0.94, -0.37), P <
      0.0001). CONCLUSIONS: As well as supporting the results of previous studies by
      providing evidence of inefficient global processing, this review has provided
      evidence of superior local processing, which supports the WCC hypothesis in ED.

PMID- 24882146
TI  - Functionalization of biomass carbonaceous aerogels: selective preparation of
      MnO2@CA composites for supercapacitors.
AB  - Functionalized porous carbon materials with hierarchical structure and developed
      porosity coming from natural and renewable biomass have been attracting
      tremendous attention recently. In this work, we present a facile and scalable
      method to synthesize MnO2 loaded carbonaceous aerogel (MnO2@CA) composites via
      the hydrothermal carbonaceous (HTC) process. We employ two reaction systems of
      the mixed metal ion precursors to study the optimal selective adsorption and
      further reaction of MnO2 precursor on CA. Our experimental results show that the
      system containing KMnO4 and Na2S2O3.5H2O exhibits better electrochemical
      properties compared with the reaction system of MnSO4.H2O and (NH4)2S2O8. For the
      former, the obtained MnO2@CA displays the specific capacitance of 123.5 F.g(-1).
      The enhanced supercapacitance of MnO2@CA nanocomposites could be ascribed to both
      electrochemical contributions of the loaded MnO2 nanoparticles and the porous
      structure of three-dimensional carbonaceous aerogels. This study not only
      indicates that it is vital for the reaction systems to match with porous
      carbonaceous materials, but also offers a new fabrication strategy to prepare
      lightweight and high-performance materials that can be used in energy storage
      devices. 

PMID- 24882147
TI  - The mental health of Australian elite athletes.
AB  - OBJECTIVES: Currently, little is known about the prevalence of mental disorders
      in athletes. This study aims to investigate Australian elite athletes' symptoms
      of general psychological distress and common mental disorders. DESIGN: A cross
      sectional survey design was employed to assess self-reported symptom prevalence.
      METHODS: A total of 224 elite athletes (118 female, 106 male) from national
      sporting organisations in Australia were administered a self-report internet
      based survey comprising measures of demographic status and mental health
      symptoms. RESULTS: Overall, 46.4% of athletes were experiencing symptoms of at
      least one of the mental health problems assessed. Percentages meeting criteria
      for mental disorders were similar to previous epidemiological studies of both
      international athlete and community samples: depression (27.2%), eating disorder
      (22.8%), general psychological distress (16.5%), social anxiety (14.7%),
      generalised anxiety disorder (7.1%), and panic disorder (4.5%). Injured athletes
      had higher levels of both symptoms of depression (t=3.23, p=.001) and generalised
      anxiety disorder (t=2.26, p=.025). CONCLUSIONS: The level of symptoms of mental
      health problems reported by elite athletes appears similar to that observed in
      the community. However, caution must be exercised in interpreting the findings,
      as possible demographic differences between athletes and comparison population
      datasets may exist. Furthermore, self-selection of respondents in the present
      study may have reduced the representativeness of the sample and the validity of
      the comparisons. Athletes, particularly those currently injured, should be well
      supported to seek help for mental disorders through access to mental health
      professionals.

PMID- 24882149
TI  - Current concepts in the surgical management of glioma patients.
AB  - The scientific basis for the surgical management of patients with glioma is
      rapidly evolving. The infiltrative nature of these cancers precludes a surgical
      cure, but despite this, cytoreductive surgery remains central to high-quality
      patient care. In addition to tissue sampling for accurate histopathological
      diagnosis and molecular genetic characterisation, clinical benefit from
      decompression of space-occupying lesions and microsurgical cytoreduction has been
      reported in patients with different grades of glioma. By integrating advanced
      surgical techniques with molecular genetic characterisation of the disease and
      targeted radiotherapy and chemotherapy, it is possible to construct a programme
      of personalised surgical therapy throughout the patient journey. The goal of
      therapeutic packages tailored to each patient is to optimise patient safety and
      clinical outcome and must be delivered in a multidisciplinary setting. Here we
      review the current concepts that underlie surgical subspecialisation in the
      management of patients with glioma.

PMID- 24882148
TI  - [LDL-cholesterol control in patients with genetic dyslipidemia followed up by
      Lipid and Vascular Risk Units of the Spanish Society of Arteriosclerosis].
AB  - OBJECTIVE: To evaluate low-density lipoprotein-cholesterol (LDLc) achieved in
      patients with genetic dyslipidemia treated during one year in Lipid and Vascular
      Risk Units (LVRU) of the Spanish Society of Arteriosclerosis (SSA). DESIGN:
      Observational, longitudinal, retrospective, multicenter national study that
      included consecutive patients of both sexes over 18 years of age referred due to
      dyslipidemia to LVRU of the SSA. Information was collected from medical records
      corresponding to two visits in the lipid unit. RESULTS: A total of 527 patients
      (mean age 48 years, 60.0% men) diagnosed with genetic dyslipidemia (241 with
      heterozygous familial hypercholesterolemia, and 286 with familial combined
      hyperlipidemia) were included. The mean follow-up was 12.9 months. In the last
      visit, 94% were taking statins, one third combined with ezetimibe, although only
      41% were taking a high-intensity hypolipidemic treatment. Overall, 28.5% of
      patients attained an LDLc level<100 mg/dL, 35.8% decreased their LDLc by >50%,
      and 53.8% achieved one of the two. Predictors of target LDLc levels in the
      multivariate analysis were age, smoking habit and the presence of vascular
      disease. CONCLUSION: Over half of the patients with genetic dyslipidemia followed
      up by LVRU of SSA achieve LDLc objectives after one year of follow-up. The use of
      high-intensity hypolipidemic treatment could improve these results.

PMID- 24882151
TI  - Neural correlates of human-animal distinction: an ERP-study on early categorical
      differentiation with 4- and 7-month-old infants and adults.
AB  - For infants it is crucial to differentiate conspecifics from other animates in
      order to profoundly learn about the world, the self, and other people. The
      current study investigates brain correlates of a categorical human-animal
      distinction in infants of different age groups as well as in adults. Using the
      categorical oddball task (Pauen, Wahl, & Hoehl, 2011), we compared event-related
      potentials of 4- and 7-month-old infants with those of adults. A total of 100
      different-looking pictures of animals and humans were presented in random
      sequence. In 80% of the trials exemplars of one category were shown (standards),
      and in 20% of the trials exemplars of the contrasting category were shown
      (oddballs). In 7-month-olds, an increased Nc response was found for oddballs as
      compared to standards, independent of the oddball category. Furthermore,
      amplitude of the P400 was increased in reaction to standards as compared to
      oddballs, when humans served as standards (i.e., in the human-standard
      condition). No corresponding ERP-effects were observed in 4-month-olds. Thus,
      while 7-month-olds showed signs of categorical differentiation on the neural
      level, 4-month-olds' ERPs suggest less stable category representations within the
      categorical oddball paradigm. In adults, we found an increased N1 amplitude for
      oddballs as compared to standards. Thus, adults' sensitivity to the relative
      frequencies of the contrasted categories at the level of the N1 was comparable to
      infants' Nc response at 7 months. Furthermore, in adults we found the N2
      amplitude to reflect category-specific processing, with a consistently increased
      amplitude in reaction to animals. 

PMID- 24882150
TI  - The emerging role of soluble HLA-G in the control of chemotaxis.
AB  - HLA-G is an immunosuppressive molecule, that impairs the function of different
      immune cell populations, both in physiological and pathological conditions. Here,
      we have analyzed data obtained by our group and others regarding sHLA-G
      concentration in plasma from patients with different diseases. Next, we have
      summarized novel data regarding the impairment of chemotaxis of different immune
      effector cells mediated by sHLA-G. Finally, we have discussed the impact of this
      function on the immune response during cancer, viral infection, autoimmunity, and
      on B cell differentiation in secondary lymphoid organs. In conclusion, we have
      delineated a role of sHLA-G in the control of chemotaxis of immune effector
      cells, that may be relevant to modulate immune responses in different settings. 

PMID- 24882152
TI  - Intervertebral disc and stem cells cocultured in biomimetic extracellular matrix
      stimulated by cyclic compression in perfusion bioreactor.
AB  - BACKGROUND CONTEXT: Intervertebral disc (IVD) degeneration often causes back
      pain. Current treatments for disc degeneration, including both surgical and
      nonsurgical approaches, tend to compromise the disc movement and cannot fully
      restore functions of the IVD. Instead, cell-based IVD tissue engineering seems
      promising as an ultimate therapy for IVD degeneration. PURPOSE: To tissue
      engineer an IVD ex vivo as a biological substitute to replace degenerative IVD.
      STUDY DESIGN: An extracellular matrix (ECM) structure-mimetic scaffold,
      cocultured human IVD cells and human mesenchymal stem cells (hMSCs), and
      mechanical stimulation were used to biofabricate a tissue-engineered IVD.
      METHODS: An optimal ratio of human annulus fibrosus (hAF) cells to hMSCs for AF
      generation within aligned nanofibers, and that of human nucleus pulposus (hNP)
      cells to hMSCs for NP generation within hydrogels were first determined after
      comparing different coculture ratios of hAF or hNP cells to hMSCs. Nanofibrous
      strips seeded with cocultured hAF cells/hMSCs were constructed into multilayer
      concentric rings, enclosing an inner core of hydrogel seeded with hNP
      cells/hMSCs. A piece of nonwoven nanofibrous mat seeded with hMSC-derived
      osteoblasts was assembled on the top of the cellular nanofiber/hydrogel assembly,
      as an interface layer between the cartilagenous end plate and vertebral body. The
      final assembled construct was then maintained in an osteochondral cocktail medium
      and stimulated with compressive loading to further enhance the hAF and hNP cells
      differentiation and increase the IVD ECM production. RESULTS: Among all
      cocultured groups, hAF cells and hMSCs in the ratio of 2:1 cultured in nanofibers
      showed the closest mRNA expression levels of AF-related markers to positive
      control hAF cells, whereas hNP cells and hMSCs in the ratio of 1:2 cultured in
      hydrogels showed the closest expression levels of NP-related markers to positive
      control hNP cells. The effects of compressive loading on chondrogenesis of hAF or
      hNP cell and hMSC coculture were dependent on the scaffold structure; the
      expression of cartilage-related markers in AF nanofibers was downregulated,
      whereas that in NP hydrogel was upregulated. Interestingly, we found that hMSC
      derived osteogenic cells in the interface layer were turned into chondrogenic
      lineage cells, with decreased expression of osteogenic markers and increased
      expression of chondrogenic markers. CONCLUSIONS: We demonstrate a unique approach
      using a biomimetic scaffold, IVD and stem cell coculture, and mechanical
      stimulation to tissue-engineer a biological IVD substitute. The results show that
      our approach provides both favorable physical and chemical cues through cell
      matrix and cell-cell interactions and mechanobiological induction to enhance IVD
      generation ex vivo. Our findings may lead to viable tissue engineering
      applications of generating a functional biological IVD for the treatment of disc
      degeneration.

PMID- 24882153
TI  - Cortisol awakening response and diurnal cortisol among children at elevated risk
      for schizophrenia: relationship to psychosocial stress and cognition.
AB  - Abnormal hypothalamic-pituitary-adrenal (HPA) axis function, as indexed by
      elevated diurnal cortisol levels and/or a blunted cortisol awakening response
      (CAR), has been observed among patients with first episode psychosis and
      associated with neurocognitive deficits in this population. However, the extent
      to which these features precede illness onset is unclear. The current study aimed
      to determine whether children who are at putatively elevated risk for psychosis
      because they present multiple antecedents of schizophrenia (ASz), and high-risk
      children with a family history of illness (FHx), are characterized by abnormal
      cortisol levels when compared with their typically developing (TD) peers. A
      further aim was to investigate the extent to which cortisol levels are associated
      with psychosocial stress and neurocognitive function. Thirty-three ASz children,
      22 FHx children, and 40 TD children were identified at age 9-12 years using a
      novel community-based screening procedure or as relatives of individuals with
      schizophrenia. All participants were antipsychotic-naive and not currently
      seeking treatment for their symptoms. At age 11-14 years, participants provided
      salivary cortisol samples and completed psychosocial stress measures and tests of
      memory and executive function. Results indicated that FHx children, but not ASz
      children, were characterized by a blunted CAR relative to their TD peers (effect
      size=-0.73, p=0.01) that was not explained by psychosocial stress exposure or by
      distress relating to these experiences. Neither FHx nor ASz children were
      characterized by elevated diurnal cortisol. Among both FHx and ASz children, more
      pronounced HPA axis function abnormalities (i.e., higher diurnal cortisol levels
      and greater blunting of the CAR) were associated with poorer performance on tests
      of verbal memory and executive function. These findings support the notion that
      at least some HPA axis abnormalities described in psychosis precede illness
      onset, rather than being a subsequent epiphenomenon. We speculate that the
      blunted CAR may constitute an early (potentially genetically mediated) marker of
      psychosis vulnerability, whilst elevated diurnal cortisol levels may emerge only
      proximally to disease onset. 

PMID- 24882154
TI  - Chronic stress increases vulnerability to diet-related abdominal fat, oxidative
      stress, and metabolic risk.
AB  - BACKGROUND: In preclinical studies, the combination of chronic stress and a high
      sugar/fat diet is a more potent driver of visceral adiposity than diet alone, a
      process mediated by peripheral neuropeptide Y (NPY). METHODS: In a human model of
      chronic stress, we investigated whether the synergistic combination of highly
      palatable foods (HPF; high sugar/fat) and stress was associated with elevated
      metabolic risk. Using a case-control design, we compared 33 post-menopausal
      caregivers (the chronic stress group) to 28 age-matched low-stress control women
      on reported HPF consumption (modified Block Food Frequency Questionnaire),
      waistline circumference, truncal fat ultrasound, and insulin sensitivity using a
      3-h oral glucose tolerance test. A fasting blood draw was assayed for plasma NPY
      and oxidative stress markers (8-hydroxyguanosine and F2-Isoprostanes). RESULTS:
      Among chronically stressed women only, greater HPF consumption was associated
      with greater abdominal adiposity, oxidative stress, and insulin resistance at
      baseline (all p's<=.01). Furthermore, plasma NPY was significantly elevated in
      chronically stressed women (p<.01), and the association of HPF with abdominal
      adiposity was stronger among women with high versus low NPY. There were no
      significant predictions of change over 1-year, likely due to high stability
      (little change) in the primary outcomes over this period. DISCUSSION: Chronic
      stress is associated with enhanced vulnerability to diet-related metabolic risk
      (abdominal adiposity, insulin resistance, and oxidative stress). Stress-induced
      peripheral NPY may play a mechanistic role.

PMID- 24882156
TI  - Differences in HPA-axis and heart rate responsiveness to psychosocial stress in
      children with autism spectrum disorders with and without co-morbid anxiety.
AB  - Children and adolescents with autism spectrum disorder (ASD) have much higher
      rates of anxiety disorders relative to their typically developing peers. However,
      there have been few attempts to investigate what physiological parameters may be
      associated with this elevated rate of anxiety. Therefore, this study investigated
      the physiological correlates of anxiety in ASD, with a focus on whether measures
      of heart rate and cortisol responsiveness to psychosocial stress differentiate
      those participants with ASD with and without a co-occurring anxiety disorder. A
      total of 75 male participants aged 10-16 years with normal intellectual ability
      underwent a psychosocial stress test. The participants included healthy controls
      (n=23), ASD only (ASD; n=20) and ASD with a comorbid anxiety disorder (ASDanx;
      n=32). Heart rate, heart rate variability and salivary cortisol were compared by
      fitting a piecewise regression model to examine baseline levels and change over
      time within and between the rest, stress and recovery phases of the stress test.
      The ASDanx group had different response patterns from both the ASD and control
      groups. The ASDanx group was characterized by a blunted cortisol and heart rate
      response to psychosocial stress. Furthermore, in the ASDanx group, reduced heart
      rate and cortisol responsiveness were significantly related to increased anxiety
      symptoms. This is the first study to report a possible physiological basis for co
      occurring anxiety disorders in children and adolescents with ASD. It is possible
      that a non-adaptive physiological response to psychosocial stress may be related
      to the high prevalence of co-occurring anxiety disorders in people with ASD. 

PMID- 24882157
TI  - Inhaled vasopressin increases sociability and reduces body temperature and heart
      rate in rats.
AB  - The neuropeptides vasopressin (AVP) and oxytocin (OT) have therapeutic potential
      across a range of psychiatric disorders. However, there is uncertainty about the
      effectiveness of the intranasal route of administration that is often used to
      deliver these neuropeptides. Recent preclinical studies, typically involving
      anesthetized or restrained animals, have assessed intranasal AVP or OT effects,
      and have obtained somewhat inconsistent results. Here we obtained intranasal
      administration of AVP in rats by nebulizing the peptide (1ml of 5 or 10mg/ml
      solution) into a small enclosed chamber over a 2min period in which well
      habituated, unanesthetized, unrestrained, rats were placed. Rats were immediately
      removed from the chamber and tested in the social interaction test, or assessed
      for changes in heart rate and body temperature using biotelemetry. Results showed
      that rats exposed to nebulized AVP (5 or 10mg/ml) showed increased social
      proximity (adjacent lying) and decreased anogenital sniffing in the social
      interaction test. Biotelemetry showed substantial and long lasting (>1h)
      hypothermic and bradycardic effects of nebulized AVP. These behavioral and
      physiological effects of nebulized AVP mimic those observed in recent studies
      with peripherally injected AVP. Plasma AVP concentrations were substantially
      increased 10min after nebulized AVP, producing levels above those seen with a
      behaviorally effective injected dose of AVP (0.005mg/kg intraperitoneal). This
      study thus provides a novel and effective method for neuropeptide administration
      to rodents. 

PMID- 24882155
TI  - Plasma oxytocin concentrations following MDMA or intranasal oxytocin in humans.
AB  - MDMA (+/-3,4-methylenedioxymethamphetamine, 'ecstasy') is reportedly used
      recreationally because it increases feelings of sociability and interpersonal
      closeness. Prior work suggests that the pro-social effects of MDMA may be
      mediated by release of oxytocin. A direct examination of plasma levels of
      oxytocin after acute doses of oxytocin and MDMA, in the same individuals, would
      provide further evidence for the idea that MDMA produces its pro-social effects
      by increasing oxytocin. Fourteen healthy MDMA users participated in a 4-session,
      double-blind study in which they received oral MDMA (0.75 and 1.5mg/kg),
      intranasal oxytocin (20IU or 40IU), and placebo. Plasma oxytocin concentrations,
      as well as cardiovascular and subjective effects were assessed before and at
      several time points after drug administration. MDMA (1.5mg/kg only) increased
      plasma oxytocin levels to a mean peak of 83.7pg/ml at approximately 90-120min,
      compared to 18.6pg/ml after placebo. Intranasal oxytocin (40IU, but not 20IU)
      increased plasma oxytocin levels to 48.0pg/ml, 30-60min after nasal spray
      administration. MDMA dose-dependently increased heart rate, blood pressure,
      feelings of euphoria (e.g., 'High' and 'Like Drug'), and feelings of sociability,
      whereas oxytocin had no cardiovascular or subjective effects. The subjective and
      cardiovascular responses to MDMA were not related to plasma oxytocin levels,
      although the N was small for this analysis. Future studies examining the effects
      of oxytocin antagonists on responses to MDMA will help to determine the mechanism
      by which MDMA produces pro-social effects. 

PMID- 24882158
TI  - Relation of progesterone and DHEAS serum levels to 5-HT1A receptor binding
      potential in pre- and postmenopausal women.
AB  - Preclinical research and clinical experience point to a modulation of 5-HT1A
      receptor expression by gonadal steroid hormones. We examined the effect of
      estradiol, progesterone and DHEAS on serotonin neurotransmission in 16
      premenopausal and 28 postmenopausal women, differentiating by reproductive
      status. By means of positron emission tomography and the radiotracer [carbonyl
      (11)C]WAY-100635, the 5-HT1A receptor binding potential (BP) was quantified in 45
      brain regions of interest. Median BP was used as a surrogate marker to estimate
      the whole brain effect of the steroid hormones on receptor binding. We found a
      strong negative effect of serum progesterone and DHEAS levels on 5-HT1A receptor
      binding in postmenopausal women both in the Median BP and on a regional level.
      Furthermore, there was a non-linear, U-shaped relationship between DHEAS levels
      and 5-HT1A receptor binding in the pooled sample. Presynaptic 5-HT1A receptor BP
      in the raphe nuclei was significantly explained in a non-linear way by both
      progesterone and DHEAS in the pooled sample. Our study confirms in humans a
      preclinically suggested relation of the steroid hormones progesterone and DHEAS
      to 5-HT1A receptor binding. We show differential effects of the hormones with
      regard to reproductive hormonal status. Non-linear, U-shaped relationships
      between hormone serum concentrations and serotonin neurotransmission might
      explain paradoxical effects of these hormones on mood. 

PMID- 24882159
TI  - Age-dependent sensitivity to glucocorticoids in the developing mouse basolateral
      nucleus of the amygdala.
AB  - Experiences of severe trauma during childhood are thought to be risk factors for
      developing mental disorders, such as anxiety and mood disorders, later in life.
      Correspondingly, exposure of rodents to early-life stress has been shown to
      affect neuronal circuitry and emotional behavior in adulthood, indicating a
      significant impact of stress on brain development. One current hypothesis
      proposes that the developing central nervous system is more sensitive to
      environmental influences, such as stress, than the adult. To test this
      hypothesis, we compared long-lasting effects of systemic corticosterone (CORT)
      administrations in two distinct early developmental periods. Mice exposed to
      early-neonatal CORT treatment on postnatal days (PD) 2-4 exhibited strongly
      enhanced excitability of neurons of the basolateral nucleus of the amygdala (BLA)
      in early adolescence and displayed impaired extinction of contextually
      conditioned fear memory, a type of behavior in which the BLA plays an important
      role. Furthermore, gene-expression of NMDA receptor subunits as well as calcium
      activated K(+)-channels was reduced in the amygdala. In contrast, exposure to the
      same CORT concentrations in a late-neonatal period (PD17-19) did not
      significantly affect BLA electrophysiology or extinction learning in adolescence.
      These results suggest age-dependent consequences of neonatal CORT exposure in
      amygdala neurons and provide evidence for a detrimental influence of early
      neonatal stress on adolescent fear-memory processing. 

PMID- 24882160
TI  - Selective lentiviral-mediated suppression of microRNA124a in the hippocampus
      evokes antidepressants-like effects in rats.
AB  - Several lines of evidences suggest that the brain-derived neutrophic factor
      (BDNF) is implicated in the pathophysiology of depression. However, the molecular
      mechanisms are not fully understood. In the current study we aimed to investigate
      how genetic modulation of BDNF in the hippocampus using microRNa124a (miR124a)
      expressing lentiviral vectors (LV) might affect depression-like behavior in adult
      rats. For this purpose, we assessed the expression level of miR124a and its
      direct target BDNF in the hippocampus and the cortex after 21-days exposure to
      social defeat stress. Results demonstrated that miR124a was up-regulated in the
      hippocampus but not in the cortex. In contrast, and as expected, BDNF transcripts
      were down-regulated. In a different set of experiments, male Wistar rats received
      bilateral intra-hippocampal or intra-cortical infusions of BDNF- and miR124a
      expressing lentiviral vectors and depression-like behavior was assessed after 21
      days social defeat stress using the novelty suppressed feeding, the sucrose
      preference and the forced swim tests. The results indicated that miR124a
      overexpression exacerbated depression-like behavior. However, an anti-depressant
      like effect was observed when BDNF or miR124a-silencers (siR124a) were injected
      into the hippocampus. Importantly, when expressed into the cortex, LV-miR124a, LV
      siR124a and LV-BDNF had no effect on depression. Our findings indicate that
      hippocampal miR124a and its direct target BDNF play an important role in
      depression-like behavior. Taken together, the current results reveal, for the
      first time, a potential molecular regulation of miR124a on BDNF, and the
      pronounced behavioral consequences of this regulation shed light on the
      mechanisms underlying BDNF anti-depressant potential. 

PMID- 24882161
TI  - Do venepuncture procedures induce cortisol responses? A review, study, and
      synthesis for stress research.
AB  - Venepuncture procedures are frequently employed to continuously monitor humoral
      stress markers. As such procedures are conceived as "potent psychological and
      physiological stressors", there is a need to determine whether venepuncture
      procedures themselves elicit cortisol responses and if so, how to deal with them
      appropriately. In order to assess the rate of cortisol responses to venepuncture,
      we conducted a literature review, which suggested that venepuncture procedures
      induce cortisol responses with a probability of approximately 30%. By utilizing
      Bayesian analysis, this result was integrated with the cortisol data of 18
      healthy men who were exposed to a venepuncture procedure twice (time lag: 1
      week). The currently observed response rate of 47% differed substantially from
      the earlier findings, which we attribute to a self-selective sampling of
      participants. In addition, participants showing a response to the first
      venepuncture were highly likely to also show a response to the second one. In
      this regard, we discuss the presumed conditioning of cortisol responses to
      venepuncture procedures. To prevent the superposition of venepuncture-induced
      cortisol responses and responses induced by target stressors, we propose a time-
      and selection-based strategy: cortisol samples taken about 110min after
      venepuncture should be virtually adjusted for its superimposing effects.
      Furthermore, previous experiences of venepuncture were highly predictive for
      cortisol responsiveness. This association could be utilized in further studies to
      identify participants who will probably show a cortisol response to venepuncture.

PMID- 24882162
TI  - Cellular mechanisms of cortisol in heart failure.

PMID- 24882163
TI  - Stress enhances reconsolidation of declarative memory.
AB  - Retrieval of negative emotional memories is often accompanied by the experience
      of stress. Upon retrieval, a memory trace can temporarily return into a labile
      state, where it is vulnerable to change. An unresolved question is whether post
      retrieval stress may affect the strength of declarative memory in humans by
      modulating the reconsolidation process. Here, we tested in two experiments
      whether post-reactivation stress may affect the strength of declarative memory in
      humans. In both experiments, participants were instructed to learn neutral,
      positive and negative words. Approximately 24h later, participants received a
      reminder of the word list followed by exposure to the social evaluative cold
      pressor task (reactivation/stress group, nexp1=20; nexp2=18) or control task
      (reactivation/no-stress group, nexp1=23; nexp2=18). An additional control group
      was solely exposed to the stress task, without memory reactivation (no
      reactivation/stress group, nexp1=23; nexp2=21). The next day, memory performance
      was tested using a free recall and a recognition task. In the first experiment we
      showed that participants in the reactivation/stress group recalled more words
      than participants in the reactivation/no-stress and no-reactivation/stress group,
      irrespective of valence of the word stimuli. Furthermore, participants in the
      reactivation/stress group made more false recognition errors. In the second
      experiment we replicated our observations on the free recall task for a new set
      of word stimuli, but we did not find any differences in false recognition. The
      current findings indicate that post-reactivation stress can improve declarative
      memory performance by modulating the process of reconsolidation. This finding
      contributes to our understanding why some memories are more persistent than
      others. 

PMID- 24882164
TI  - Assessing gonadal hormone contributions to affective psychopathologies across
      humans and animal models.
AB  - Despite increasing acknowledgement of hormonal contributions to mood and anxiety
      disorders, the underlying mechanisms by which gonadal hormones influence
      psychopathology-related behaviours remain unknown. This review focuses on recent
      research that examines the influence of gonadal steroid hormones, including
      androgens, oestrogens, and progesterone, on mood and anxiety-related behaviours
      in human health and disease. To this aim, the literature was surveyed for studies
      that assess conditions with suspected underlying hormonal imbalances in otherwise
      healthy participants (e.g., premenstrual dysphoric disorder, postmenopausal
      depression) as well as conditions linked to congenital endocrine abnormalities
      (e.g., Turner Syndrome, Klinefelter Syndrome, polycystic ovary syndrome,
      congenital adrenal hyperplasia, familial male precocious puberty, androgen
      insensitivity syndrome). Furthermore, to better inform clinical work and to
      create a translational bridge, a second goal was to set human psychopathologies
      and animal models of these conditions side-by-side. In the second part of the
      review, based on consistencies revealed in the existing literature across
      conditions, a new model for the impact of gonadal hormones on anxious and
      depressed behavioural states is proposed. Finally, we conclude by proposing
      directions for future research, including the development of specific tasks
      suitable for cross-species comparisons to increase our knowledge of the role of
      gonadal hormones in mood and anxiety. 

PMID- 24882165
TI  - Acute hypernatremia dampens stress-induced enhancement of long-term potentiation
      in the dentate gyrus of rat hippocampus.
AB  - Stress often occurs within the context of homeostatic threat, requiring
      integration of physiological and psychological demands to trigger appropriate
      behavioral, autonomic and endocrine responses. However, the neural mechanism
      underlying stress integration remains elusive. Using an acute hypernatremic
      challenge (2.0M NaCl subcutaneous), we assessed whether physical state may affect
      subsequent responsiveness to psychogenic stressors. We found that experienced
      forced swimming (FS, 15min in 25 degrees C), a model of psychogenic stress,
      enhanced long-term potentiation (LTP) induction in the dentate gyrus (DG) of the
      rat hippocampus ex vivo. The effect of FS on LTP was prevented when the animals
      were adrenalectomized or given mineralocorticoid receptor antagonist RU28318
      before experiencing stress. Intriguingly, relative to normonatremic controls,
      hypernatremic challenge effectively elevated plasma sodium concentration and
      dampened FS-induced enhancement of LTP, which was prevented by adrenalectomy. In
      addition, acute hypernatremic challenge resulted in increased extracellular
      signal-regulated kinase (ERK)1/2 phosphorylation in the DG and occluded the
      subsequent activation of ERK1/2 by FS. Moreover, stress response dampening
      effects by acute hypernatremic challenge remained intact in conditional oxytocin
      receptor knockout mice. These results suggest that acute hypernatremic challenge
      evokes a sustained increase in plasma corticosterone concentration, which in turn
      produces stress-like changes in the DG, thereby occluding subsequent
      responsiveness to psychogenetic stress. They also fit into the general concept of
      "metaplasticity" - that is, the responsiveness to stress is not fixed but appears
      to be governed by the recent history of prior physical state. 

PMID- 24882166
TI  - Association of pro-inflammatory cytokines, cortisol and depression in patients
      with chronic obstructive pulmonary disease.
AB  - Evidence suggests that pro-inflammatory cytokines and cortisol play a crucial
      role in the etiology of chronic obstructive pulmonary disease (COPD) and
      depression. Depression occurs commonly among COPD patients and an earlier
      diagnosis would be beneficial. This study investigated the associations between
      depression, sputum cytokines and salivary cortisol in COPD patients. The diurnal
      rhythms of sputum IL-1, IL-6, TNF-alpha and salivary cortisol were measured in
      COPD patients with depression compared to those only with depression, or COPD and
      healthy controls. The area under the diurnal variation curves (AUC) over the 24h
      time course and relative diurnal variation (VAR) were calculated while
      correlation and regression analysis were performed. Patients with co-morbid
      depression and COPD showed an increasing sputum IL-1, sputum TNF-alpha AUC and a
      decreasing salivary cortisol VAR (P<0.001). The combination of sputum TNF-alpha
      AUC, sputum IL-1 AUC, sputum IL-6 AUC and salivary cortisol VAR performed best as
      a potential biomarker in the diagnosis of depression in COPD patients, with a
      sensitivity of 94.74% and a specificity of 96.67%. Positive correlations were
      found between sputum IL-1 AUC and sputum TNF-alpha AUC versus depressive
      symptoms, respectively a negative correlation was found between salivary cortisol
      VAR and depression. They were independently associated with depression in
      logistic regression models. Depression in COPD is associated with higher 24-h
      overall levels of sputum IL-1, TNF-alpha and flattened diurnal salivary cortisol.
      These non-invasive sputum and salivary biomarkers may serve as a simple clinical
      tool for the early diagnosis of depression in COPD patients. 

PMID- 24882168
TI  - Improved fatty acid analysis of conjugated linoleic acid rich egg yolk
      triacylglycerols and phospholipid species.
AB  - Reports from chicken conjugated linoleic acid (CLA) feeding trials are limited to
      yolk total fatty acid composition, which consistently described increased
      saturated fatty acids and decreased monounsaturated fatty acids. However,
      information on CLA triacylglycerol (TAG) and phospholipid (PL) species is
      limited. This study determined the fatty acid composition of total lipids in CLA
      rich egg yolk produced with CLA-rich soy oil, relative to control yolks using gas
      chromatography with flame ionization detection (GC-FID), determined TAG and PL
      fatty acid compositions by thin-layer chromatography-GC-FID (TLC-GC-FID),
      identified intact PL and TAG species by TLC-matrix-assisted laser
      desorption/ionization mass spectrometry (TLC-MALDI-MS), and determined the
      composition of TAG and PL species in CLA and control yolks by direct flow
      infusion electrospray ionization MS (DFI ESI-MS). In total, 2 lyso-phosphatidyl
      choline (LPC) species, 1 sphingomyelin species, 17 phosphatidyl choline species,
      19 TAG species, and 9 phosphatidyl ethanolamine species were identified. Fifty
      percent of CLA was found in TAG, occurring predominantly in C52:5 and C52:4 TAG
      species. CLA-rich yolks contained significantly more LPC than did control eggs.
      Comprehensive lipid profiling may provide insight on relationships between lipid
      composition and the functional properties of CLA-rich eggs. 

PMID- 24882167
TI  - Differential neural responses to child and sexual stimuli in human fathers and
      non-fathers and their hormonal correlates.
AB  - Despite the well-documented importance of paternal caregiving for positive child
      development, little is known about the neural changes that accompany the
      transition to fatherhood in humans, or about how changes in hormone levels affect
      paternal brain function. We compared fathers of children aged 1-2 with non
      fathers in terms of hormone levels (oxytocin and testosterone), neural responses
      to child picture stimuli, and neural responses to visual sexual stimuli. Compared
      to non-fathers, fathers had significantly higher levels of plasma oxytocin and
      lower levels of plasma testosterone. In response to child picture stimuli,
      fathers showed stronger activation than non-fathers within regions important for
      face emotion processing (caudal middle frontal gyrus [MFG]), mentalizing (temporo
      parietal junction [TPJ]) and reward processing (medial orbitofrontal cortex
      [mOFC]). On the other hand, non-fathers had significantly stronger neural
      responses to sexually provocative images in regions important for reward and
      approach-related motivation (dorsal caudate and nucleus accumbens). Testosterone
      levels were negatively correlated with responses to child stimuli in the MFG.
      Surprisingly, neither testosterone nor oxytocin levels predicted neural responses
      to sexual stimuli. Our results suggest that the decline in testosterone that
      accompanies the transition to fatherhood may be important for augmenting empathy
      toward children. 

PMID- 24882169
TI  - Dasabuvir: A Non-Nucleoside Inhibitor of NS5B for the Treatment of Hepatitis C
      Virus Infection.
AB  - Hepatitis C virus (HCV) chronically infects about 2% of the world's population.
      Approximately a quarter of these patients will develop, during their life, liver
      cirrhosis, which entails a high risk of complications and death. Successful
      antiviral therapy can reduce the risk of disease progression, but it is feasible
      only in a minority of patients because it includes interferon which is
      contraindicated in the most advanced stages of the disease and in patients with
      severe impairment of other organs. Consequent to the launch of the first direct
      antiviral agents (DAA), namely the protease inhibitors telaprevir and boceprevir,
      several molecules are in an advanced phase of clinical development to be used in
      association with interferon or with other DAA (in interferon-free combinations).
      This review focuses on the mechanism of action, pharmacokinetics, efficacy,
      safety and resistance of dasabuvir, a non-nucleoside inhibitor of NS5B viral RNA
      dependent RNA polymerase. Thanks to its pharmacokinetics, dasabuvir can be
      administered twice daily. In combinations with other oral DAAs, dasabuvir results
      in very high rates of SVR (about 95%) in patients with HCV genotype 1 infection
      with a good tolerability and safety. In conclusion, dasabuvir is a good agent to
      be used in interferon-free combinations for the treatment of chronic hepatitis C.

PMID- 24882170
TI  - Prevalence and determinants of antenatal depression among pregnant women in a
      predominantly rural population in Ghana: the DON population-based study.
AB  - BACKGROUND: While depression during pregnancy is one of the strongest risk
      factors for postnatal depression, it has been comparatively little studied,
      particularly in sub-Saharan Africa. METHODS: Cohort study nested within 4-weekly
      surveillance of all women of reproductive age to identify pregnancies and collect
      data on births and deaths in the Kintampo Health Research Centre study area of
      Ghana. Women were screened for depression during pregnancy using the Patient
      Health Questionnaire to ascertain DSM-IV major or minor depression. Information
      on demographic factors, indicators of social and economic disadvantage, and
      previous obstetric history were also collected which were examined using logistic
      regression; effect sizes reported as relative risks with 95% confidence
      intervals. RESULTS: 21,135 pregnant women were screened of whom 20,920 (98.9%)
      had complete data on potential determinants. 2086 (9.9%, 95% CI: 9.5%-10.3%) had
      AND. Determinants of AND were: maternal age 30+ years (relative risk [RR], 1.16
      (1.06-1.27); never married ([RR] 1.34, (1.14-1.58); lower wealth quintile ([RR],
      1.30 (1.13-1.50); unplanned pregnancy ([RR], 1.55 (1.43-1.69); previous pregnancy
      loss ([RR], 1.30 (1.18-1.43). LIMITATIONS: We did not assess women for physical
      health during pregnancy, and lacked information on some potentially relevant
      psychosocial factors. CONCLUSION: Prevalence of antenatal depression, applying
      clinical criteria, is similar to that seen in high income countries. Factors
      related to chronic social and economic disadvantage are among the most important
      co-determinants. Population-level interventions that address these problems among
      women of reproductive age may be the most effective strategy for reducing the
      prevalence and impact of depression in pregnancy.

PMID- 24882171
TI  - The hospital anxiety and depression scale--dimensionality, reliability and
      construct validity among cognitively intact nursing home patients.
AB  - BACKGROUND: Depression and anxiety are particularly common among individuals
      living in long-term care facilities. Therefore, access to a valid and reliable
      measure of anxiety and depression among nursing home patients is highly
      warranted. AIM: To investigate the dimensionality, reliability and construct
      validity of the Hospital Anxiety and Depression scale (HADS) in a cognitively
      intact nursing home population. METHODS: Cross-sectional data were collected from
      two samples; 429 cognitively intact nursing home patients participated,
      representing 74 different Norwegian nursing homes. Confirmative factor analyses
      and correlations with selected constructs were used. RESULTS: The two-factor
      model provided a good fit in Sample1, revealing a poorer fit in Sample2. Good
      acceptable measurement reliability was demonstrated, and construct validity was
      supported. LIMITATIONS: Using listwise deletion the sample sizes were 227 and
      187, for Sample1 and Sample2, respectively. Greater sample sizes would have
      strengthen the statistical power in the tests. The researchers visited the
      participants to help fill in the questionnaires; this might have introduced some
      bias into the respondents' reporting. The 14 HADS items were part of greater
      questionnaires. Thus, frail, older NH patients might have tired during the
      interview causing a possible bias. CONCLUSION: Low reliability for depression was
      disclosed, mainly resulting from three items appearing to be inappropriate
      indicators for depression in this population. Further research is needed
      exploring which items might perform as more reliably indicators for depression
      among nursing home patients.

PMID- 24882172
TI  - Corpus callosum size may predict late-life depression in women: a 10-year follow
      up study.
AB  - BACKGROUND: Recent research on late-life depression (LLD) pathophysiology
      suggests the implication of abnormalities in cerebral white matter and
      particularly in interhemispheric transfer. Corpus callosum (CC) is the main brain
      interhemispheric commissure. Hence, we investigated the association between
      baseline CC measures and risk of LDD. METHODS: We studied 467 non-demented
      individuals without LLD at baseline from a cohort of elderly community-dwelling
      people (the ESPRIT study). LLD was assessed at year 2, 4, 7 and 10 of the study
      follow-up. At baseline, T1-weighted magnetic resonance images were manually
      traced to measure the mid-sagittal areas of the anterior, mid and posterior CC.
      Multivariate Cox proportional hazards models stratified by sex were used to
      predict LLD incidence over 10 years. RESULTS: A significant interaction between
      gender and CC size was found (p=0.02). LLD incidence in elderly women, but not in
      men, was significantly associated with smaller anterior (HR 1.37 [1.05-1.79]
      p=0.017), mid (HR 1.43 [1.09-1.86] p=0.008), posterior (HR 1.39 [1.12-1.74]
      p=0.002) and total (HR 1.53 [1.16-2.00] p=0.002) CC areas at baseline in Cox
      models adjusted for age, education, global cognitive impairment, ischemic
      pathologies, left-handedness, white matter lesion, intracranial volume and past
      depression. LIMITATIONS: The main limitation was the retrospective assessment of
      major depression. CONCLUSION: Smaller CC size is a predictive factor of incident
      LLD over 10 years in elderly women independently of cognitive deterioration. Our
      finding suggests a possible role of CC and reduced interhemispheric connectivity
      in LLD pathophysiology. Extensive explorations are needed to clarify the
      mechanisms leading to CC morphometric changes in mood disorders.

PMID- 24882173
TI  - The effect of exercise on hippocampal volume and neurotrophines in patients with
      major depression--a randomized clinical trial.
AB  - BACKGROUND: The hippocampal volume is reduced in patients with major depression.
      Exercise leads to an increased hippocampal volume in schizophrenia and in healthy
      old adults. The effect of exercise on hippocampal volume is potentially mediated
      by brain derived neurotrophic factor (BDNF), vascular endothelial growth factor
      (VEGF), and insulin like growth factor 1 (IGF-1). The aim of this trial was to
      assess the effect of an aerobic exercise intervention on hippocampal volume and
      serum BDNF, VEGF, and IGF-1 in patients with major depression. METHODS: Patients
      were randomized to an aerobic exercise intervention (n=41) or a control condition
      (n=38). Both interventions consisted of three supervised sessions per week during
      a three months period. RESULTS: Post-intervention the increase in maximal oxygen
      uptake was 3.90 ml/kg/min (SD 5.1) in the aerobic exercise group and 0.95
      ml/kg/min (SD 6.2) in the control group (p=0.03). The hippocampal volume, BDNF,
      VEGF, or IGF-1 did not differ between the two groups. Post-hoc we found a
      positive association between change in hippocampal volume and verbal memory
      (Rho=0.27; p=0.05) and change in hippocampal volume and depressive symptoms
      (Rho=0.30; p=0.03). LIMITATIONS: Participation was low in both groups
      corresponding to an average participation of one session per week. CONCLUSION:
      Despite a significant increase in maximal oxygen uptake, a pragmatic exercise
      intervention did not increase hippocampal volume or resting levels of
      neurotrophines in out-patients with mild to moderate major depression. Trial
      identifier: ClinicalTrials.gov (NCT00695552).

PMID- 24882174
TI  - Observing nonreactively: a conditional process model linking mindfulness facets,
      cognitive emotion regulation strategies, and depression and anxiety symptoms.
AB  - BACKGROUND: Mindfulness-based interventions for depression and anxiety emphasize
      the importance of observing present moment experience, but observing has often
      been positively related to anxiety and unrelated to depression symptoms. The
      current study sought to better understand the conditions and mechanism through
      which observing relates to symptoms by examining six conditional process models
      in which (1) nonreactivity moderates the direct effect of observing on symptoms
      of anxiety and depression symptoms and (2) nonreactivity moderates the indirect
      effect of observing on anxiety and depression via cognitive emotion regulation
      strategies (i.e., rumination, worry, and reappraisal). METHODS: A clinical sample
      of 189 adults with anxiety and depressive disorders completed the Five Facet
      Mindfulness Questionnaire, Mood and Anxiety Symptom Questionnaire, Penn State
      Worry Questionnaire, Ruminative Responses Scale, and Emotion Regulation
      Questionnaire. RESULTS: Conditional process models showed that nonreactivity
      significantly moderated the direct effect of observing on symptoms of depression,
      but not anxiety. Additionally, nonreactivity significantly moderated the indirect
      effect of observing on symptoms of depression through rumination and reappraisal,
      but not worry. For anxiety, nonreactivity significantly moderated the indirect
      effect of observing on symptoms through worry and rumination, but not
      reappraisal. LIMITATIONS: Causal interpretations of results are limited.
      CONCLUSION: Findings suggest that the relationship between observing and symptoms
      of depression and anxiety depends on the capacity to observe nonreactively, which
      may influence symptoms directly and indirectly through cognitive emotion
      regulation strategies. Findings raise important implications for tailoring
      mindfulness-based treatments for anxiety and depression symptoms.

PMID- 24882175
TI  - Common mental and musculoskeletal disorders as predictors of disability
      retirement among Finns.
AB  - BACKGROUND: The contribution of common mental disorders (CMD) co-occurring with
      chronic musculoskeletal disorders (MSD) to disability retirement is not known.
      METHODS: A nationally representative sample (the Health 2000 survey) comprised
      3943 occupationally active Finns aged 30-63. MSD and other chronic disorders were
      assessed by a physician in a standardized clinical examination, and CMD using the
      Composite International Diagnostic Interview. Disability pension data for 2000
      2011 was retrieved from national pension records. Cox regression was used with
      censoring for death and pension other than that for disability. Covariate
      information was based on an interview. RESULTS: The baseline prevalence of CMD
      was 9.4% and of MSD 31.1%. CMD co-occurred with MSD in 3.3% of participants. The
      risks inflicted by CMD and MSD were additive. Thirty-eight per cent of the co
      morbid subjects, 18% of those with CMD and 19% of those with MSD retired
      prematurely during the average follow-up of 8.6 years. Compared with those with
      neither type of disorder, the hazard ratio (HR) for disability pension was 2.4
      (95% CI 1.7-2.7) for CMD only, 2.2 (1.8-2.7) for MSD only, and 4.1 (2.9-5.7) for
      the occurrence of both, allowing for age, gender, other chronic disorders,
      working conditions, and socio-economic and lifestyle factors. No synergistic or
      antagonistic interactive effects were observed. LIMITATIONS: The determinants
      were measured only once and we had no information on incident disorders during
      the follow-up. CONCLUSIONS: It is important to identify subjects with both mental
      and musculoskeletal complaints in order to efficiently support their work
      ability.

PMID- 24882176
TI  - Effectiveness of transdiagnostic Internet cognitive behavioural treatment for
      mixed anxiety and depression in primary care.
AB  - BACKGROUND: Internet-delivered cognitive behavioural treatment (iCBT) has been
      shown to be effective for the combined treatment of depression and anxiety in
      randomised controlled trials. The degree to which these findings generalise to
      patients in primary care awaits further investigation. METHODS: Using an open
      trial design, we investigated adherence to, and effectiveness of a 6-lesson
      therapist-assisted iCBT program for mixed anxiety and depression for patients (n
      = 707) who completed the program under the supervision of primary care clinicians
      (general practitioners, psychologists and other allied health professionals).
      Primary outcome measures were the PHQ-9 (depression), GAD-7 (generalised
      anxiety), K-10 (distress), WHODAS-II (disability), mini-SPIN (social anxiety) and
      panic disorder severity scale self-report version (PDSS). RESULTS: Adherence to
      the iCBT program was modest (47.3%), but within-subjects effect sizes ranged from
      medium (0.51 for PDSS) to large (1.20 for PHQ-9). LIMITATIONS: The lack of
      control group, limited post-treatment data due to drop-out, and short follow-up
      period. CONCLUSIONS: iCBT is an effective treatment for mixed depression and
      anxiety when delivered in primary care settings. Methods to increase adherence
      are needed to optimise the benefits to patients.

PMID- 24882177
TI  - Near-term predictors of the intensity of suicidal ideation: an examination of the
      24 h prior to a recent suicide attempt.
AB  - BACKGROUND: The extent to which acute exposures such as alcohol use (AU) and
      negative life events (NLE) are uniquely associated with intensity of suicidal
      ideation during the hours leading up to a suicide attempt is unknown. The main
      aim of the current study was to quantify the unique effect of acute exposures on
      next-hour suicidal ideation when adjusting for previous hour acute exposures and
      suicidal ideation. An exploratory aim of the current study was to examine the
      effect of non-alcohol drug use (DU) on suicidal ideation. METHODS: Participants
      included 166 (61.0% female) recent suicide attempters presenting to a Level 1
      trauma hospital. A timeline follow-back methodology was used to assess acute
      exposures and intensity of suicidal ideation within the 24h prior to the suicide
      attempt. RESULTS: Findings indicated that acute AU (b=.20, p<.01) and NLE (b=.58,
      p<.01) uniquely predicted increases in next-hour suicidal ideation, over and
      above previous hour suicidal ideation, whereas acute DU did not. LIMITATIONS: The
      current study's methodology provides continuous hourly snapshots prior to the
      suicide attempt, quite close to when it happened, but is retrospective and
      causality cannot be inferred. CONCLUSIONS: Understanding that, within a patient,
      AU and NLE predict near-term increases in suicidal ideation has practical utility
      impacting providers' clinical decision-making, safety concerns, and ultimate
      determination of level of risk for suicide.

PMID- 24882178
TI  - Characteristic distributions of regional cerebral blood flow changes in major
      depressive disorder patients: a pseudo-continuous arterial spin labeling (pCASL)
      study.
AB  - BACKGROUND: Most previous studies that examined regional cerebral blood flow
      (rCBF) abnormalities in major depressive disorder (MDD) required the injection of
      radioisotopes into subjects. Here by using magnetic resonance imaging (MRI) with
      the pseudo-continuous arterial spin labeling (pCASL) method which does not
      require radioisotopes, we examined rCBF in patients with MDD in comparison with
      that in patients with schizophrenia and healthy subjects, taking the regional
      cerebral gray matter volume into account. METHODS: Subjects were 27 patients with
      MDD, 42 with schizophrenia and 43 healthy volunteers who underwent 3-T MRI with
      pCASL. Obtained pCASL imaging data were subject to the voxel-by-voxel statistical
      analysis. RESULTS: There were significant reductions of rCBF in the right
      inferior prefrontal cortex and anterior cingulate cortices (ACCs) in the MDD
      patients compared with the healthy controls. When compared with the schizophrenic
      patients, the MDD patients showed lower rCBF in the subgenual ACC and higher rCBF
      in left occipital region. LIMITATION: The abnormalities of rCBF in MDD were known
      to reverse during symptom remission. Further study with follow-up period would
      bring the perception about the treatment response. CONCLUSION: The rCBF reduction
      in the subgenual region may be a specific functional abnormality to MDD patients,
      which may provide a biological marker for MDD. The MRI with pCASL method is a
      promising tool to detect rCBF abnormalities controlling for gray matter volume in
      psychiatric disorders.

PMID- 24882179
TI  - G-protein beta3 subunit genetic variation moderates five-year depressive symptom
      trajectories of primary care attendees.
AB  - BACKGROUND: Genetic variation in the G-protein beta3 subunit (GNB3) has
      previously been associated with gene splicing that has been further linked to
      increased signal transduction and major depressive disorder. However, the effect
      of GNB3 genetic variation on depressive symptom trajectories is currently
      unknown. The aim of the present study is to examine whether genetic variation in
      GNB3 moderates depressive symptom trajectories among 301 primary care attendees
      enrolled in the Diagnosis, Management and Outcomes of Depression in Primary Care
      (diamond) prospective cohort study. METHODS: Depressive symptoms were assessed
      using three measures: (1) DSM-IV criteria, (2) Primary Care Evaluation of Mental
      Disorders Patient Health Questionnaire-9 (PHQ-9), and (3) Center for
      Epidemiologic Studies Depression Scale (CESD). DSM-IV criteria were measured at
      baseline, 24, 36, 48, and 60 months post-baseline, whereas, PHQ-9 and CESD
      measurements were taken at baseline, 12, 24, 36, 48, and 60 months post-baseline.
      Two haplotype-tagging single nucleotide polymorphisms [rs5443 (C825T) and rs5440]
      spanning the GNB3 gene including ~1Kb upstream and downstream of the gene
      boundaries were genotyped. RESULTS: Five-year PHQ-9 and CESD depressive symptom
      trajectories were moderated by rs5440. Carriers of the rs5440 GG genotype had
      more favourable depressive symptom trajectories compared to AG or AA genotype
      carriers. The rs5443 polymorphism did not moderate depressive symptom
      trajectories, regardless of the measure used. LIMITATIONS: Generalizability to
      depressed populations outside of the primary care setting may be limited.
      CONCLUSIONS: These results provide novel evidence suggesting genetic variation in
      the 5-prime region of GNB3 moderates depressive symptom trajectories among
      primary care attendees.

PMID- 24882180
TI  - Increased suicide attempts in young depressed patients with abnormal temporal
      parietal-limbic gray matter volume.
AB  - BACKGROUND: Suicide is a major cause of death throughout the world. Approximately
      60% of all suicides have a history of depression. Previous studies of structural
      brain imaging have shown that suicide is often associated with abnormal fronto
      limbic networks. However, the mechanism underlying suicide in depression remains
      poorly understood. METHOD: Twenty sex- and age-matched suicidal unipolar patients
      were compared with 18 non-suicidal unipolar patients and 28 healthy controls.
      High-resolution T1-weighted 3T magnetic resonance imaging (MRI) scans were
      acquired. Hamilton Depressive Rating Scale (HAMD) and Self-Rating Depression
      scale (SDS) were evaluated. The criterion for suicidality was one or more
      documented lifetime suicide attempts. A whole-brain optimized voxel-based
      morphometry (VBM) approach was applied. The Dysfunctional Attitude Scale (DAS)
      was used to measure cognitive scheme in depressive patients. RESULTS: Compared
      with controls, patients without suicide history showed significant decreased gray
      matter volume in the left insula lobe [-35 18 9], whereas patients with suicide
      history showed significantly decreased gray matter volume in the right middle
      temporal gyrus [60 -53 -8] and increased gray matter volume in the right parietal
      lobe [39 -39 60]. Compared with the non-suicidal depressed patient group, the
      suicidal group showed significant decreased gray matter volume in left limbic
      cingulated gyrus [-2 -21 28]. Moreover, the gray matter volume values in this
      significantly different brain region were negatively correlated with
      dysfunctional attitude scores in suicidal depressed patients. LIMITATIONS: This
      study needs replication and further clarification in a larger patient population.
      CONCLUSIONS: Suicide attempts in young depressed patients may be related to
      abnormal gray matter volumes in temporal-parietal-limbic networks. Specifically,
      small left limbic cingulate gyrus volumes may be a candidate for the prediction
      of suicide in young depressed patients.

PMID- 24882181
TI  - Childhood maltreatment and the course of bipolar disorders among adults:
      epidemiologic evidence of dose-response effects.
AB  - BACKGROUND: Childhood maltreatment (CM) is highly prevalent among individuals
      with bipolar disorders (BP); however few studies have examined its potential role
      in the course and outcome of individuals with BP. We aim to examine the dose
      response relationship between the number of types of CM and the course of
      individuals with BP. METHODS: As part of the National Epidemiologic Survey on
      Alcohol and Related Conditions, 1600 adults who met lifetime DSM-IV criteria for
      BP-I (n=1172) and BP-II (n=428) were included. Individuals were evaluated using
      the Alcohol Use Disorder and Associated Disabilities Interview Schedule-DMS-IV
      Version and data was analyzed lifetime and from Waves 1 and 2, approximately 3
      years apart. RESULTS: Around half of individuals with BP had a history of at
      least one type of CM. Overall, there was a clear dose-response relationship
      between number of CM and severity of BP across several domains, including
      clinical characteristics, probability of treatment, lifetime prevalence of
      psychiatric comorbidity, incidence of anxiety disorders, substance use disorder,
      and nicotine dependence, and level of psychosocial functioning. LIMITATIONS: The
      interviews were conducted by lay professional interviewers rather than
      clinicians, use of retrospective report to determine CM in individuals with BP,
      and not all respondents from Wave 1 were able to be interviewed in Wave 2.
      CONCLUSIONS: The number of types of CM confers developmental differences in the
      course of BP with a worse course and outcome of BP. Early identification and
      treatment of CM are warranted to improve the course and outcome of individuals
      with BP.

PMID- 24882183
TI  - The costs of social anxiety disorder: the role of symptom severity and
      comorbidities.
AB  - BACKGROUND: Social anxiety disorder (SAD) is associated with low direct costs
      compared to other anxiety disorders while indirect costs tend to be high. Mental
      comorbidities have been identified to increase costs, but the role of symptom
      severity is still vague. The objective of this study was to determine the costs
      of SAD, and to explore the impact of symptoms and comorbidities on direct and
      indirect costs. METHODS: Baseline data, collected within the SOPHO-NET multi
      centre treatment study (N=495), were used. Costs were calculated based on health
      care utilization and lost productivity. Symptom severity was measured with the
      Liebowitz-Social-Anxiety-Scale; comorbidities were included as covariates.
      RESULTS: Total 6-month costs were accrued to ?4802; 23% being direct costs. While
      there was no significant association with SAD symptom severity for direct costs,
      costs of absenteeism increased with symptom severity in those with costs >0;
      comorbid affective disorders and eating disorders had an additional effect. Self
      rated productivity was lower with more pronounced symptoms even after controlling
      for comorbidities. LIMITATIONS: As the study was based on a clinical sample total
      costs were considered, rather than net costs of SAD and no population costs could
      be calculated. DISCUSSION: The burden associated with lost productivity was
      considerable while costs of healthcare utilization were rather low as most
      patients had not sought for treatment before. Efforts to identify patients with
      SAD earlier and to provide adequate treatment should be further increased. Mental
      comorbidities should be addressed as well, since they account for a large part of
      indirect costs associated with SAD.

PMID- 24882182
TI  - Further evidence that severe scores in the aggression/anxiety
      depression/attention subscales of child behavior checklist (severe dysregulation
      profile) can screen for bipolar disorder symptomatology: a conditional
      probability analysis.
AB  - BACKGROUND: Previous work shows that children with high scores (2SD, combined
      score>=210) on the Attention Problems, Aggressive Behavior, and Anxious-Depressed
      (A-A-A) subscales of the Child Behavior Checklist (CBCL) are more likely than
      other children to meet criteria for bipolar (BP)-I disorder. However, the utility
      of this profile as a screening tool has remained unclear. METHODS: We compared
      140 patients with pediatric BP-I disorder, 83 with attention deficit
      hyperactivity disorder (ADHD), and 114 control subjects. We defined the CBCL
      Severe Dysregulation profile as an aggregate cutoff score of >=210 on the A-A-A
      scales. Patients were assessed with structured diagnostic interviews and
      functional measures. RESULTS: Patients with BP-I disorder were significantly more
      likely than both control subjects (Odds Ratio [OR]: 173.2; 95% Confidence
      Interval [CI], 21.2 to 1413.8; P<0.001) and those with ADHD (OR: 14.6; 95% CI,
      6.2 to 34.3; P<0.001) to have a positive CBCL-Severe Dysregulation profile.
      Receiver Operating Characteristics analyses showed that the area under the curve
      for this profile comparing children with BP-I disorder against control subjects
      and those with ADHD was 99% and 85%, respectively. The corresponding positive
      predictive values for this profile were 99% and 92% with false positive rates of
      <0.2% and 8% for the comparisons with control subjects and patients with ADHD,
      respectively. LIMITATIONS: Non-clinician raters administered structured
      diagnostic interviews, and the sample was referred and largely Caucasian.
      CONCLUSIONS: The CBCL-Severe Dysregulation profile can be useful as a screen for
      BP-I disorder in children in clinical practice.

PMID- 24882184
TI  - Characteristics of initial fearful spells and their associations with DSM-IV
      panic attacks and panic disorder in adolescents and young adults from the
      community.
AB  - BACKGROUND: Few studies examined characteristics of initial fearful spells (FS)
      or panic attacks (PA) and their relation to DSM-IV PA and panic disorder (PD).
      METHODS: A community sample of adolescents and young adults (N=3021) was followed
      up in 4 waves (T0-T3) over up to 10 years. FS, PA, and PD were assessed at each
      wave using the DSM-IV/M-CIDI. Characteristics of the initial FS/PA including
      perceived reasons/triggers, appraisal, duration, and behavioral/emotional
      consequences of the initial FS/PA were retrospectively assessed at T1 and T2 in
      those reporting the experience of lifetime FS or PA at these waves (N=363).
      Multinomial logistic regressions adjusted for sex and age were used to reveal
      associations of initial FS/PA characteristics (aggregated data from T1 and T2)
      with PA only (N=88) and PD (N=62; lifetime incidences cumulated across assessment
      waves) (reference group: No PA/PD). RESULTS: Alcohol consumption,
      drugs/medication, and physical illness as perceived reasons for the initial FS/PA
      were associated with PA-only (OR 2.46-5.44), while feelings of depression,
      feelings of anxiety, and having always been anxious/nervous as perceived reasons
      for the initial FS/PA, appraising the initial FS/PA as terrible and long-term
      irritating/burdensome, subsequent feelings of depression, subsequent avoidance,
      and subsequent consumption of medication, alcohol, or drugs were associated with
      PD (OR 2.64-4.15). A longer duration until "feeling okay again" was associated
      with both PA-only (OR=1.29 per category) and PD (OR=1.63). LIMITATIONS: Initial
      FS/PA characteristics were necessarily assessed retrospectively by self-report
      only. Thus, our data might be subject to recall/evaluation biases. Aggregated
      data were used and strictly prospective-longitudinal studies are necessary that
      replicate our findings. CONCLUSION: Assessing initial FS/PA characteristics might
      be useful to identify individuals at increased risk for more severe panic
      pathology.

PMID- 24882185
TI  - Cannabis use and first manic episode.
AB  - BACKGROUND: Cannabis is the most commonly abused drug among patients with bipolar
      disorder. Available data has shown that the risk of psychotic disorders increases
      with the frequency and intensity of cannabis abuse. The present purpose was to
      review relevant studies to investigate whether cannabis use can be linked to the
      onset of mania in bipolar disorder. METHODS: Articles published between 1972 and
      December 2013 were searched on Medline and PsychInfo using the following
      keywords: first manic episode, or onset mania, or bipolar disorder and cannabis.
      Relevant papers cited in the references of selected articles were further
      considered for inclusion into the review. RESULTS: Lifetime use of cannabis among
      bipolar patients appears to be around 70% and approximately 30% of patients with
      a bipolar disorder present a comorbidity of cannabis abuse or dependence.
      Cannabis use is associated with younger age at onset of first mania and with more
      frequent depressive or manic episodes, although the evidence is somewhat
      inconsistent. Likewise cannabis consumption is related to poorer outcome and an
      increased risk of rapid cycling or mixed episodes. In contrast, neuro-cognitive
      functioning seems to be positively affected in patients with psychiatric
      comorbidity. While cannabis use often precedes first manic episodes, the causal
      direction remains to be determined. LIMITATIONS: Variations in definition of
      cannabis use/dependence. Lack of controlled studies limiting definite conclusions
      about a putative causal relationship between cannabis and onset of mania.
      CONCLUSIONS: Further investigations are needed to clarify the relationships
      between cannabis use and first manic episode.

PMID- 24882186
TI  - An investigation of temperament and character inventory items for predicting the
      response to paroxetine treatment in patients with major depressive disorder.
AB  - BACKGROUND: Previous studies have reported associations between Temperament and
      Character Inventory (TCI) dimension scores and the response to treatment in
      patients with major depressive disorder (MDD). We aimed to determine which TCI
      items could predict the response to treatment with paroxetine in patients with
      MDD. METHODS: Seventy-three patients were enrolled in this study. The
      participants were treated with 10-40mg/day of paroxetine for six weeks; they then
      completed the TCI. The Montgomery-Asberg Depression Rating Scale (MADRS) was used
      to evaluate the patients. The participants were divided into two groups
      (responders and non-responders). We used a chi-squared test to identify the 10
      items with the strongest association with treatment response from among all 240
      items on the TCI, and we used a multiple logistic regression analysis to confirm
      the validity of these 10 items. RESULTS: Among the TCI dimension scores, only the
      C score differed significantly between the two groups. We analyzed 10 models
      using each of the 10 best items. All the models significantly predicted treatment
      response. The TCI dimensions model also significantly predicted treatment
      response, but its predictive value was lower than those of the other 10 models.
      LIMITATIONS: The responders included the early responders. The results lacked
      information about responders whose responses were not predicted by the logistic
      regression models and TCI items. CONCLUSIONS: Some TCI items showed significant
      associations with the response to paroxetine treatment in the patients with MDD.
      Treatment response in patients with MDD may be predicted using only 10 items from
      the TCI.

PMID- 24882187
TI  - Predictors of 30-year mortality in depressed and comparison samples.
AB  - BACKGROUND: Although higher rates of depression and lower rates of social
      behaviors (i.e., social support and activities) and physical activities are
      associated with mortality, the independent contribution of each of these factors
      needs examination. METHODS: A prospective sample of 848 individuals (55% female)
      was used; half were clinically depressed at baseline; the other half comprised a
      comparison sample matched on census tract, gender, and marital status. Depressive
      symptoms, social behaviors, and physical activities were examined as time-varying
      predictors of mortality over a 30-year period using multiple imputation for
      missing data and Cox proportional hazards regression, controlling for demographic
      factors and health risk factors. RESULTS: By the end of the study, 137
      individuals from the depressed sample and 99 individuals from the comparison
      sample had died. Although the mortality rate is higher in the depressed sample,
      after controlling for demographic, health risk factors, social behaviors, and
      physical activity, there was no significant difference in mortality between the
      depressed and control samples. Among participants in the depressed sample,
      reduced participation in social activities was significantly associated with a
      higher risk of mortality. LIMITATIONS: Frequency and intensity of activities were
      not assessed and all data except for mortality were self-report. CONCLUSIONS:
      Promoting social engagement through activities may hold promise for delaying
      mortality among individuals who are depressed. Potential methods to promote
      social engagement and factors such as positive emotions that should be considered
      in future studies are discussed.

PMID- 24882188
TI  - Depression among university students in Kenya: prevalence and sociodemographic
      correlates.
AB  - BACKGROUND: Depression is a common cause of morbidity but prevalence levels among
      Kenyan university students are poorly understood. A better understanding of
      depression and its correlates is essential in planning for appropriate
      interventions in this population group. METHOD: A random sample of 923 University
      of Nairobi students (525 male and 365 female) were interviewed using a
      questionnaire to record sociodemographic variables. Depressive symptoms were
      measured using Centre for Epidemiological Studies Short Depression Scale (CES - D
      10). RESULTS: The mean age was 23 (s.d. 4.0). Using a cut-off point of 10, the
      overall prevalence of moderate depressive symptoms was 35.7% (33.5% males and
      39.0% females) and severe depression was 5.6% (5.3% males and 5.1% female).
      Depressive illness was significantly more common among the first year students,
      those who were married; those who were economically disadvantaged and those
      living off campus. Other variables significantly related to higher depression
      levels included year of study, academic performance, religion and college
      attended. Logistic regression showed that those students who used tobacco,
      engaged in binge drinking and those who had an older age were more likely to be
      depressed. No difference was noted with respect to gender. LIMITATIONS: This was
      a cross sectional study relying on self report of symptoms and could therefore be
      inaccurate. Although the study was conducted in the largest university in the
      country that admits students from diverse backgrounds in the country there could
      still be regional differences in other local universities. CONCLUSION: Depression
      occurs in a significant number of students. Appropriate interventions should be
      set up in higher institutions of learning to detect and treat these disorders
      paying particular attention to those at risk.

PMID- 24882189
TI  - Concurrent occurrence of multiple positive lifestyle behaviors and depression
      among adults in the United States.
AB  - BACKGROUND: To our knowledge, no studies have examined the dose-response
      association between concurrent occurrence of multiple positive health behaviors
      and depression. As a result, the purpose of this study was to examine the dose
      response association between concurrent occurrence of lifestyle behaviors (i.e.,
      diet, physical activity, and smoking) on depression symptoms among a national
      sample of U.S. adults (20-85 yr). METHODS: Using data from the 2005-2006 NHANES
      (n=2574), diet was assessed from the healthy eating index variable; physical
      activity was assessed via accelerometry; smoking was assessed from cotinine
      levels; and depression was assessed from the Patient Health Questionnaire 9 (PHQ
      9). RESULTS: Each lifestyle behavior was independently associated with depression
      in the expected direction, and there was also evidence of a dose-response
      relationship. Compared to those having 0 positive lifestyle factors, those with
      1, 2, and 3 positive lifestyle factors, respectively, were 15% (p=0.38), 67%
      (p=0.001), and 82% (p=0.01) less likely to be classifed as having moderate or
      greater depression symptoms (PHQ-9 >=10). LIMITATIONS: The main limitation of
      this study was the cross-sectional design. CONCLUSION: there is a dose-response
      relationship between concurrent occurrence of positive lifestyle behaviors and
      depression symptoms.

PMID- 24882190
TI  - Uric acid levels may be a biological marker for the differentiation of unipolar
      and bipolar disorder: the role of affective temperament.
AB  - BACKGROUND: The aim of this study was to investigate whether uric acid levels are
      different between patients with remission period of bipolar disorder type I (BD)
      and patients with remission period of major depressive disorder (MDD). METHODS:
      For this aim 41 patients diagnosed with BD and 30 patients diagnosed with
      recurrent MDD according to DSM-IV who were in remission period for at least 8
      weeks were evaluated consecutively. The median age and gender distribution of the
      two groups were similar. Subjects with comorbid psychiatric diagnosis and/or
      severe medical illnesses were excluded. Affective temperament was evaluated with
      TEMPS-A (Temperament Evaluation of Memphis, Pisa, Paris and San Diego
      Autoquestionnaire). Plasma uric acid levels were recorded in mg/dl. RESULTS: The
      uric acid levels of BD patients were found higher than patients with MDD and
      healthy controls. Additionally uric acid levels of MDD patients were lower than
      patients with BD and healthy subjects (F=4.183, p=0.039). A moderate correlation
      between hyperthymic and irritable temperament scores and uric acid levels was
      detected in both patient groups and in healthy controls. A negative correlation
      was observed between depressive temperament and uric acid levels only in MDD
      group. LIMITATIONS: The measurements of temperament were estimated depending on
      the patient's statement. The medications that patients used were not controlled.
      CONCLUSION: There is a purinergic dysfunction not only in BD but also in MDD
      patients. High uric acid levels are associated with hyperthymic and irritable
      temperament scores whereas low uric acid levels are associated with depressive
      temperament scores.

PMID- 24882191
TI  - Association between toll-like receptor 2 gene diversity and early-onset bipolar
      disorder.
AB  - BACKGROUND: Toll-like receptor 2 (TLR2) molecules play a pivotal role in innate
      immune responses by their ability to recognize and sense a wide repertoire of
      infectious and endogenous cellular structural elements. Here we evaluated whether
      genetic variants in TLR2 influence the age of the disease onset in bipolar
      disorder (BD). METHODS: DNAs from 571 BD patients 229 early-onset (EO-BD) and 342
      late-onset (LO-BD) and 199 healthy controls (HC) were analyzed for the following
      TLR2 polymorphisms: the 5'-UTR -196 to -174 insertion/deletion (ins/del), the
      intron 1 rs4696480 A/T, and the exon 3 rs3804099 C/T and rs3804100 C/T. PHASE
      software was used for haplotype reconstruction. Genetic associations were
      examined using a chi-square test. RESULTS: We found that the TLR2 rs3804099 TT
      was significantly more prevalent in EO-BD than in LO-BD patients (corrected p
      (pc)=0.024). After excluding family history of psychiatric disorders, we also
      found that the TLR2 rs4696480 TT genotype was significantly more prevalent in EO
      BD as compared to LO-BD and controls (pc=0.002 and 0.002). Homozygous state for
      the insTTT haplotype, carrying the above mentioned risk genotypes, was
      significantly more frequent in EO-BD than in LO-BD patients (pc=0.007) and in EO
      BD without family history of psychiatric disorders as compared to (i) those with
      positive history (pc=0.03), (ii) with LO-BD without family history (pc=0.001) and
      (iii) with HC (pc=0.009). LIMITATIONS: Confirmation by replication in independent
      BD cohorts is warranted. CONCLUSIONS: Our data suggest the potential role of TLR2
      genetic variants in the pathogen-mediated susceptibility to BD.

PMID- 24882192
TI  - Effectiveness of community facilitator training in improving knowledge,
      attitudes, and confidence in relation to depression and suicidal behavior:
      results of the OSPI-Europe intervention in four European countries.
AB  - BACKGROUND: Community facilitators (CFs), such as teachers, nurses and social
      workers, are well placed as gatekeepers for depression and suicidal behavior, but
      not properly prepared to provide preventive and supportive services. The current
      study aimed: (1) to improve CFs' attitudes toward depression, knowledge on
      suicide, and confidence to detect suicidal behavior in four European countries
      and (2) to identify specific training needs across regions and CF groups.
      METHODS: A standardized training program was provided to 1276 CFs in Germany,
      Hungary, Ireland, and Portugal. Attitudes toward depression, knowledge about
      suicide, and confidence in identifying suicidal persons were assessed before
      training, after training, and at three to six months follow-up. Additionally,
      several participants' characteristics were registered. RESULTS: At baseline, CFs
      showed relatively favorable attitudes toward depression, but limited knowledge on
      suicide, and little confidence to identify suicidal behavior. Basic skills
      strongly differed across CF groups and countries. For example, in Germany, carers
      for the elderly, nurses, teachers, and managers were most in need of training,
      while in Portugal pharmacists and the clergy appeared to be important target
      groups. Most importantly, the training program improved the competencies of CF
      groups across countries and these improvements were sustained after three to six
      months. CFs with low basic skills benefited most of the training. LIMITATIONS:
      The observed training effects could be influenced by other external factors as
      our results are based upon a pre-post comparison with no control group.
      CONCLUSIONS: Gatekeeper trainings in community settings are successful in
      improving knowledge, reshaping attitudes, and boosting the confidence of
      gatekeepers. The most effective strategy to achieve the preferred objectives is
      to target those CF groups that are most in need of training and to tailor the
      content of the training program to the individual needs of the target group.

PMID- 24882195
TI  - Comparing four competing models of depressive symptomatology: a confirmatory
      factor analytic study of 986,647 U.S. veterans.
AB  - BACKGROUND: Few rigorous studies have examined the factor structure of major
      depression symptoms as assessed by current diagnostic systems. This study
      evaluated four competing models of depressive symptomatology among a large,
      heterogeneous sample of U.S. veterans. METHODS: To determine the best fitting
      model of major depressive symptoms among four competing models, this study
      conducted a series of confirmatory factor analyses on a national sample of
      986,647 U.S. veterans. RESULTS: A two-factor model first reported by Krause,
      Reed, and McArdle (2010) provided superior fit to symptom-level data compared to
      three other models. The optimal model consists of a somatic factor including
      anhedonia, sleep difficulties, fatigue, appetite changes, concentration
      difficulties, and psychomotor agitation; and a non-somatic factor including
      depressed mood, feelings of worthlessness, and thoughts of death. Factorial
      invariance testing found this model to be invariant by gender and major
      depression diagnosis. LIMITATIONS: A widely used self-report measure of
      depression was used and the sample consisted solely of veterans so further study
      is needed with clinician-administered measures and non-veteran samples.
      CONCLUSIONS: Together, these findings support separating symptoms of major
      depression into somatic and non-somatic factors which may have clinical
      relevance, and help clarify debates about the factor structure of depressive
      symptoms.

PMID- 24882194
TI  - Insomnia and emotion dysregulation: independent and interactive associations with
      posttraumatic stress symptoms among trauma-exposed smokers.
AB  - INTRODUCTION: Traumatic event exposure is common among cigarette smokers, and
      elevated posttraumatic stress symptoms (PTSS) are associated with increased
      smoking levels. As such, the current study examined factors that may contribute
      to elevated PTSS among trauma-exposed smokers. Insomnia and emotion dysregulation
      may be particularly relevant among smokers, and are each associated with PTSS.
      However, it remains unclear whether these factors are associated with PTSS after
      accounting for the effects of dispositional factors and each other, and whether
      they may interact to predict PTSS. Thus, the current study sought to test whether
      insomnia and emotion dysregulation are independently associated with PTSS after
      accounting for negative affectivity and number of traumas experienced, and to
      investigate the potential interactive influence of these factors on PTSS. METHOD:
      Hypotheses were tested cross-sectionally among a community sample of trauma
      exposed individuals who presented for smoking cessation treatment (n=349).
      RESULTS: Results demonstrated that insomnia and emotion dysregulation each
      predicted elevated PTSS after controlling for the other, negative affectivity and
      number of traumas experienced. In addition, the interaction between insomnia and
      emotion dysregulation was significant, such that higher levels of insomnia and
      emotion dysregulation were associated with the most severe PTSS. LIMITATIONS:
      Future research should examine these factors among a clinical sample of
      individuals with PTSD, as well as utilize prospective designs. CONCLUSIONS:
      Findings highlight the roles of insomnia and emotion dysregulation in
      contributing to elevated PTSS among trauma-exposed smokers, and the potential
      importance of targeting these factors in the context of PTSD treatment.

PMID- 24882193
TI  - Bipolar disorder with comorbid binge eating history: a genome-wide association
      study implicates APOB.
AB  - BACKGROUND: Bipolar disorder (BD) is a highly heritable disease. While genome
      wide association (GWA) studies have identified several genetic risk factors for
      BD, few of these studies have investigated the genetic etiology of specific
      disease subtypes. In particular, BD is positively associated with eating
      dysregulation traits such as binge eating behavior (BE), yet the genetic risk
      factors underlying BD with comorbid BE have not been investigated. METHODS:
      Utilizing data from the Genetic Association Information Network study of BD,
      which included 729,454 single nucleotide polymorphisms (SNPs) genotyped in 1001
      European American bipolar cases and 1034 controls, we performed GWA analyses of
      bipolar subtypes defined by the presence or absence of BE history, and performed
      a case-only analysis comparing BD subjects with and without BE history.
      Association signals were refined using imputation, and network analysis was
      performed with Ingenuity Pathway Analysis software. Based on these results,
      candidate SNPs were selected for replication in an independent sample of 855
      cases and 857 controls. RESULTS: Top ranking SNPs in the discovery set included
      rs6006893 in PRR5, rs17045162 in ANK2, rs13233490 near PER4, rs4665788 and
      rs10198175 downstream of APOB, rs2367911 in CACNA2D1, and rs7249968 near ZNF536.
      Rs10198175 in APOB also demonstrated evidence of association in the replication
      sample and a meta-analysis of the two samples. LIMITATIONS: Without information
      of BE history in controls, it is not possible to determine whether the observed
      association with APOB reflects a risk factor for BE behavior in general or a risk
      factor for a subtype of BD with BE. Further longitudinal and functional studies
      are needed to determine the causal pathways underlying the observed associations.
      CONCLUSIONS: This study identified new potential BD-susceptibility genes,
      highlighting the advantages of phenotypic sub-classification in genetic research
      and clinical practice.

PMID- 24882196
TI  - Altered brain response to others' pain in major depressive disorder.
AB  - BACKGROUND: Empathy has a central role in successful interpersonal engagement.
      Several studies have reported altered empathy in major depressive disorder (MDD),
      which could lead to interpersonal difficulties. However, the neural basis of
      altered empathy in the disorder is still largely unknown. To address this, we
      performed functional magnetic resonance imaging that tested empathy for others'
      pain in MDD patients. METHODS: Eleven patients with MDD and 11 age-, gender-,
      handedness-, and education level-matched healthy control subjects were studied.
      We compared MDD patients and healthy controls for their regional hemodynamic
      responses to visual perception of videos showing human hands in painful
      situations. We also assessed subjective pain ratings of the videos in each group.
      RESULTS: The MDD patients showed lower pain ratings for the painful videos
      compared with the healthy controls. In addition, the MDD patients showed reduced
      cerebral activation in the left middle cingulate cortex, and the right
      somatosensory-related cortices, whereas they showed greater cerebral activation
      in the left inferior frontal gyrus. LIMITATIONS: We relied on a relatively small
      sample size and could not exclude effects of medications. CONCLUSIONS: These
      results suggest that in MDD patients the altered neural activations in these
      regions may be associated with a deficit in the identification of pain in others.
      This study adds to our understanding of the neural mechanism involved in empathy
      in MDD.

PMID- 24882197
TI  - Anxiety and depression among haematological cancer patients attending treatment
      centres: prevalence and predictors.
AB  - BACKGROUND: This study aimed to: (1) estimate the prevalence of anxiety and/or
      depression among haematological cancer patients attending treatment centres; and
      (2) explore the demographic, disease and treatment characteristics associated
      with anxiety and/or depression. METHODS: A cross-sectional study was conducted
      with outpatients from three haematology clinics in Australia. Patients with a
      confirmed diagnosis of haematological cancer were approached by a research
      assistant while waiting for their appointment and invited to participate in the
      survey. Participants completed the Hospital Anxiety and Depression Scale (HADS)
      and self-reported demographic, disease and treatment characteristics. RESULTS:
      Questionnaires from 304 participants were returned. Twenty-seven percent of
      patients reported anxiety and 17% reported depression. Specifically, 15% reported
      anxiety without depression, 5% reported depression without anxiety, and 12%
      reported comorbid anxiety and depression. Participants who had to relocate to
      receive treatment had almost three times the odds of reporting anxiety and/or
      depression compared to those who did not have to move. Former smokers also had
      significantly higher odds of reporting anxiety and/or depression. LIMITATIONS:
      The HADS is likely to have produced some false positives and false negatives when
      compared with gold standard structured clinical interviews for assessing
      psychological morbidity. CONCLUSIONS: Approximately 20% of haematological cancer
      patients attending outpatient clinics may experience clinically significant
      levels of anxiety and/or depression. Providing additional tailored support to
      patients who have had to relocate for treatment, and to former smokers, may help
      to reduce anxiety and depression among these subgroups.

PMID- 24882198
TI  - fMRI evidence for abnormal resting-state functional connectivity in euthymic
      bipolar patients.
AB  - BACKGROUND: Neural substrates of bipolar disorder (BD) have frequently been
      characterized by dysregulation of fronto-limbic networks that may persist during
      euthymic periods. Only a few studies have investigated euthymic bipolar patients
      (BP) functional connectivity at rest. The current study aims to assess resting
      state functional connectivity in euthymic BP in order to identify trait
      abnormalities responsible for enduring mood dysregulation in these patients.
      METHODS: Medial prefrontal cortex (mPFC) functional connectivity was investigated
      in 20 euthymic BP and 20 healthy subjects (HS). The functional connectivity maps
      were compared across groups using a between-group random effect analysis.
      Additional region of interest (ROI) analysis focused on mPFC-amygdala functional
      connectivity as well as correlations between the clinical features in euthymic BP
      was also conducted. RESULTS: A significant difference between euthymic BP and HS
      was observed in terms of connectivity between the mPFC and the right dorsolateral
      prefrontal cortex (dlPFC). A significant negative correlation between the
      activity of these regions was found in HS but not in euthymic BP. In addition,
      euthymic BP showed greater connectivity between mPFC and right amygdala compared
      to HS, which was also correlated with the duration of the disease. LIMITATIONS:
      The BP group was heterogeneous with respect to the bipolarity subtype and the
      medication. The robustness of results could be improved with an increased sample
      size. CONCLUSIONS: Compared to HS, the euthymic BP showed abnormal decoupling
      (decreased functional connectivity) activity between mPFC-dlPFC and
      hyperconnectivity (increased functional connectivity) and between mPFC and
      amygdala. These abnormalities could underlie the pathophysiology of BD, and may
      deteriorate further in accordance with disease duration.

PMID- 24882199
TI  - Quantity and quality of psychotherapy trials for depression in the past five
      decades.
AB  - BACKGROUND: Over the years randomized controlled trials (RCTs) of various
      psychotherapies for treating depression have provided evidence to demonstrate the
      interventions' efficacy/effectiveness. However, recent researches suggest that
      the quality of some RCTs were actually less than ideal, which could hence have
      biased their results. The present study aims to assess (1) the changes in
      characteristics of RCTs of psychotherapies for treating adult depression; (2) the
      temporal changes in their trial quality, and (3) the quality differences among
      different therapeutic approaches. METHODS: We included 135 RCTs of
      psychotherapies treating adult depression published from year 1969 to 2011.
      Temporal changes in trials' characteristics including their quantity and quality
      were assessed at study-level and arm-level. Quality differences among different
      schools of psychotherapy were assessed at arm-level. RESULTS: Changes in quantity
      and improvements in methodological quality were found at study-level. Positive
      changes in trial quality at arm-level were observed in most aspects. Comparisons
      made across different schools of psychotherapy revealed statistically significant
      differences among them, with earlier behavior therapy trials doing worst and more
      recent third wave cognitive-behavior therapy doing best. LIMITATIONS: We could
      not determine whether the observed changes in quality resulted from actual
      improvement in trial quality and/or from improved reporting. The relatively
      smaller number of arms for several types of interventions could weaken the
      representativeness when making comparisons across psychotherapeutic approaches.
      CONCLUSION: Our study revealed positive temporal changes in both trial quantity
      and quality over the past five decades and has also spotted possible areas for
      further improvement.

PMID- 24882200
TI  - Intact anger recognition in depression despite aberrant visual facial information
      usage.
AB  - BACKGROUND: Previous literature has indicated abnormalities in facial emotion
      recognition abilities, as well as deficits in basic visual processes in major
      depression. However, the literature is unclear on a number of important factors
      including whether or not these abnormalities represent deficient or enhanced
      emotion recognition abilities compared to control populations, and the degree to
      which basic visual deficits might impact this process. METHODS: The present study
      investigated emotion recognition abilities for angry versus neutral facial
      expressions in a sample of undergraduate students with Beck Depression Inventory
      II (BDI-II) scores indicative of moderate depression (i.e., >=20), compared to
      matched low-BDI-II score (i.e., <=2) controls via the Bubbles Facial Emotion
      Perception Task. RESULTS: Results indicated unimpaired behavioural performance in
      discriminating angry from neutral expressions in the high depressive symptoms
      group relative to the minimal depressive symptoms group, despite evidence of an
      abnormal pattern of visual facial information usage. LIMITATIONS: The
      generalizability of the current findings is limited by the highly structured
      nature of the facial emotion recognition task used, as well as the use of an
      analog sample undergraduates scoring high in self-rated symptoms of depression
      rather than a clinical sample. CONCLUSIONS: Our findings suggest that basic
      visual processes are involved in emotion recognition abnormalities in depression,
      demonstrating consistency with the emotion recognition literature in other
      psychopathologies (e.g., schizophrenia, autism, social anxiety). Future research
      should seek to replicate these findings in clinical populations with major
      depression, and assess the association between aberrant face gaze behaviours and
      symptom severity and social functioning.

PMID- 24882201
TI  - Lesch typology and temperament in opioid dependence: a cross-sectional study.
AB  - AIMS: The first aim of this study is to investigate the impact of different
      temperaments in opiate dependency patients. The second aim of this study is to
      define therapy relevant subgroups in opiate addiction for further basic clinical
      research and therapy. METHODS: In the time period from September to November
      2010, 101 patients (72 males and 29 females) which fulfilled the diagnosis of
      opiate dependency according to DSM-IV-TR were recruited consecutively. All
      patients were in treatment at the Oum El Nour rehabilitation center/Lebanon
      (Inpatient and Outpatient groups). Lesch Alcoholism Typology modified for
      assessment of opiate addicts, and the briefTEMPS-M, Arabic version were used.
      RESULTS: The organic Type IV group was the most prevalent (48.5%) among the
      sample followed by the Affective Type III group (41.6%) and the minority
      represented the two other types (I & II). The organic Type IV group represented
      the major type in the cyclothymic and anxious temperament. In the contrary the
      other two groups (I & II) were the minority among the cyclothymics.

PMID- 24882202
TI  - Gene-environment interaction in postpartum depression: a Chinese clinical study.
AB  - Mounting evidence has showed that both nature and nurture exert significant
      influences on the pathogenesis of neuropsychiatric diseases or psychopathologies.
      Postpartum depression (PPD) is a mental disorder that is by far under diagnosed
      and under treated, which can have a negative impact on both the maternal and the
      neonatal health. Several risk factors for PPD have been defined, including
      genetic, environmental, and hormonal. Genetically, postpartum women can be
      explained by the absence or presence of certain genetic variants that confer
      increased risk. Environmentally, postpartum women might have been exposed to
      various psychosocial risk factors. The aim of this study is to examine whether
      genetic variations of the Serotonin Transporter Promoter Variant (5-HTTLPR),
      together with environmental stressors, assessed by multiple psychological scales,
      contribute to the development of PPD symptoms. Results show that 5-HTTLPR is
      strongly associated with the major depressive disorder in postpartum women. Han
      Chinese Women who carry the long (L) allele (LL) when experiencing maternal
      pregnancy complications, prenatal maternal infection, prenatal maternal folate
      deficiency, or stressful life events during pregnancy, or had senior maternal age
      upon pregnancy (over 32.8 years old) showed higher prevalence ratios (PR) for
      symptoms of postpartum depression. 

PMID- 24882203
TI  - Management of bleeding and perforation after colonoscopy.
AB  - Bleeding is a relatively rare complication occurring mainly after snare
      polypectomy. The majority of cases can be managed successfully by endoscopic
      means leaving very few cases which will ultimately need an operation. Colonic
      perforation, on the other hand is a serious complication that requires intensive
      and careful management. Prompt recognition of the perforation during the
      procedure allows, in selected cases, immediate endoscopic closure with an
      uneventful and full recovery followed by close monitoring and surgical management
      in case of clinical deterioration. The criteria for the right selection of
      perforation cases amenable to endoscopic treatment do still need to be confirmed
      by prospective studies and further experience is required before a standard
      algorithm on the endoscopic management of perforations is developed. 

PMID- 24882204
TI  - The art and science of practice: the intersection between liberal arts and allied
      health.

PMID- 24882205
TI  - "Teens Talk Healthy Weight": the impact of a motivational digital video disc on
      parental knowledge of obesity-related diseases in an adolescent clinic.
AB  - The purpose of the study was to investigate the impact of a 7-minute educational
      and motivational weight-management digital video disc (DVD) that uses real
      patient/parent testimonials and provider-patient interactions, on adolescent and
      parent knowledge of obesity-related diseases; readiness, motivation, and self
      efficacy to lose weight; connectedness to care provider; and likelihood of return
      to clinic for follow-up care. A randomized controlled trial was conducted among
      40 overweight/obese adolescent participants (22.5% male, 77.5% female, mean
      age=15.43 years) and their parents (n=38) who visited a referral-only adolescent
      clinic for the first time from October 2009 to March 2010. Adolescents were
      randomly assigned by a research assistant to standard care alone or standard care
      plus DVD. Standard care (protocol-driven medical and nutritional assessment and
      counseling) was provided to all adolescents by a registered dietitian
      nutritionist and physician or nurse practitioner. Adolescents in the intervention
      group also viewed the DVD. Adolescents and parents completed assessments pre- and
      post-clinic visit. Repeated measures analysis of covariance was used to evaluate
      group differences, while controlling for race/ethnicity and age. Parents who
      viewed the DVD experienced greater improvements in obesity-related disease
      knowledge than parents who did not view the DVD. Adolescents in both groups
      improved on measures of motivation to lose weight and dieting self-efficacy,
      based on pre and post-test questionnaires. A 7-minute educational and
      motivational DVD helped improve parent knowledge, but was not more powerful than
      standard care alone in changing other weight-related outcomes in this adolescent
      clinic. Because it led to increased parental knowledge, incorporating the DVD
      into clinical practice could also allow more time for health providers to focus
      on specific obesity-related treatment/education. Future research might examine
      whether the DVD has more utility in different settings, such as primary care.

PMID- 24882206
TI  - The association of taste with change in adiposity-related health measures.
AB  - The relationship between taste-intensity patterns and 5-year change in adiposity
      related health measures was determined. Participants were members of the Beaver
      Dam Offspring Study, a study of the adult children of participants in the
      population-based Epidemiology of Hearing Loss Study. There were 1,918
      participants (mean baseline age=48.8 years; range=22 to 84 years) with baseline
      taste (2005 to 2008) and follow-up (2010 to 2013) data. Outcomes included 5-year
      change in body mass index, waist circumference, blood pressure, non-high-density
      lipoprotein cholesterol, and glycosylated hemoglobin A1c, and hedonic ratings of
      specific foods. Cluster analysis with Ward's minimum variance method identified
      the following 5 patterns of the suprathreshold taste intensities of salt, sweet,
      sour, and bitter: salt and sweet intensities slightly above population averages,
      average sour and bitter intensities; salt, sour, and bitter intensities above
      population average, average sweet intensity; salt, sour, and bitter intensities
      above population average, sweet intensity substantially above average; all
      intensities below population averages; and all intensities close to population
      average. The General Linear Model procedure was used for testing cluster
      differences in the outcomes. With covariate adjustment, the group with all
      intensities close to population averages had a significantly lower average
      increase in body mass index compared with the group with above-average
      intensities for salt, sour, and bitter (+0.4 vs +0.9), and in glycosylated
      hemoglobin A1c compared with the group with above-average intensities for all
      tastes (+0.20% vs +0.34%). Clusters differed in the hedonics of foods
      representing sweetness and saltiness. The study's findings provide evidence that
      perceived taste intensity might be related to changes in adiposity-related
      health. 

PMID- 24882207
TI  - Regulatory interactions between RNA and polycomb repressive complex 2.
AB  - Polycomb repressive complex 2 (PRC2) is a histone methyltransferase that is
      localized to thousands of mammalian genes. Though important to human disease and
      as a drug target, how PRC2 is recruited remains unclear. One model invokes cis
      regulatory RNA. Herein, we biochemically and functionally probe PRC2's
      recognition of RNA using the X-inactivation model. We observe surprisingly high
      discriminatory capabilities. While SUZ12 and JARID2 subunits can bind RNA, EZH2
      has highest affinity and is somewhat promiscuous. EED regulates the affinity of
      EZH2 for RNA, lending greater specificity to PRC2-RNA interactions. Intriguingly,
      while RNA is crucial for targeting, RNA inhibits EZH2's catalytic activity.
      JARID2 weakens PRC2's binding to RNA and relieves catalytic inhibition. We
      propose that RNA guides PRC2 to its target but inhibits its enzymatic activity
      until PRC2 associates with JARID2 on chromatin. Our study provides a molecular
      view of regulatory interactions between RNA and PRC2 at the chromatin interface.

PMID- 24882208
TI  - E-cadherin couples death receptors to the cytoskeleton to regulate apoptosis.
AB  - Epithelial-to-mesenchymal transition (EMT) is a cellular process essential to the
      development and maintenance of solid tissues. In cancer, EMT suppresses
      apoptosis, but the mechanisms remain unclear. EMT selectively attenuated
      apoptosis signaling via the death receptors DR4 and DR5. Loss of the epithelial
      cell adhesion protein E-cadherin recapitulated this outcome, whereas homotypic E
      cadherin engagement promoted apoptotic signaling via DR4/DR5, but not Fas.
      Depletion of alpha-catenin, which couples E-cadherin to the actin cytoskeleton,
      or actin polymerization inhibitors similarly attenuated DR4/DR5-induced
      apoptosis. E-cadherin bound specifically to ligated DR4/DR5, requiring
      extracellular cadherin domain 1 and calcium. E-cadherin augmented DR4/DR5
      clustering and assembly of the death-inducing signaling complex (DISC),
      increasing caspase-8 activation in high molecular weight cell fractions.
      Conversely, EMT attenuated DR4/DR5-mediated DISC formation and caspase-8
      stimulation. Consistent with these findings, epithelial cancer cell lines
      expressing higher E-cadherin levels displayed greater sensitivity to DR4/DR5
      mediated apoptosis. These results have potential implications for tissue
      homeostasis as well as cancer therapy.

PMID- 24882209
TI  - A cellular system that degrades misfolded proteins and protects against
      neurodegeneration.
AB  - Misfolded proteins compromise cellular function and cause disease. How these
      proteins are detected and degraded is not well understood. Here we show that
      PML/TRIM19 and the SUMO-dependent ubiquitin ligase RNF4 act together to promote
      the degradation of misfolded proteins in the mammalian cell nucleus. PML
      selectively interacts with misfolded proteins through distinct substrate
      recognition sites and conjugates these proteins with the small ubiquitin-like
      modifiers (SUMOs) through its SUMO ligase activity. SUMOylated misfolded proteins
      are then recognized and ubiquitinated by RNF4 and are subsequently targeted for
      proteasomal degradation. We further show that PML deficiency exacerbates
      polyglutamine (polyQ) disease in a mouse model of spinocerebellar ataxia 1
      (SCA1). These findings reveal a mammalian system that removes misfolded proteins
      through sequential SUMOylation and ubiquitination and define its role in
      protection against protein-misfolding diseases. 

PMID- 24882210
TI  - Tracing compartmentalized NADPH metabolism in the cytosol and mitochondria of
      mammalian cells.
AB  - Eukaryotic cells compartmentalize biochemical processes in different organelles,
      often relying on metabolic cycles to shuttle reducing equivalents across
      intracellular membranes. NADPH serves as the electron carrier for the maintenance
      of redox homeostasis and reductive biosynthesis, with separate cytosolic and
      mitochondrial pools providing reducing power in each respective location. This
      cellular organization is critical for numerous functions but complicates analysis
      of metabolic pathways using available methods. Here we develop an approach to
      resolve NADP(H)-dependent pathways present within both the cytosol and the
      mitochondria. By tracing hydrogen in compartmentalized reactions that use NADPH
      as a cofactor, including the production of 2-hydroxyglutarate by mutant
      isocitrate dehydrogenase enzymes, we can observe metabolic pathway activity in
      these distinct cellular compartments. Using this system we determine the
      direction of serine/glycine interconversion within the mitochondria and cytosol,
      highlighting the ability of this approach to resolve compartmentalized reactions
      in intact cells. 

PMID- 24882213
TI  - Epithelial-to-mesenchymal transition and cancer stem cells: emerging targets for
      novel cancer therapy.

PMID- 24882212
TI  - NAADP-sensitive two-pore channels are present and functional in gastric smooth
      muscle cells.
AB  - Nicotinic acid adenine dinucleotide phosphate (NAADP) has been identified as an
      important modulator of Ca(2+) release from the endo-lysosomal system in a variety
      of cells by a new and ubiquitous class of endo-lysosomal ion channels known as
      the two-pore channels (TPCs). However, the role of TPCs in NAADP action in smooth
      muscle is not known. In the present work, we investigated the effects of NAADP in
      gastric smooth muscle cells and its ability to release Ca(2+) by TPCs. We show
      that Ca(2+) signals mediated by NAADP were inhibited by disrupting Ca(2+)
      handling by either acidic organelles (using bafilomycin A1) or the Endoplasmic
      Reticulum (using thapsigargin, ryanodine or 2-APB). Transcripts for endogenous
      TPC1 and TPC2 were readily detected and recombinant TPCs localized to the
      endosomes and/or lysosomes. Overexpression of wild-type TPCs but not pore mutants
      enhanced NAADP-mediated cytosolic Ca(2+) signals. Desensitizing the NAADP pathway
      inhibited Ca(2+)-responses to extracellular stimulation with carbachol but not
      ATP. Taken together, these results indicate that NAADP likely induces Ca(2+)
      release from the endolysosomal system through TPCs which is subsequently
      amplified via the ER in an agonist-specific manner. Thus, we suggest a second
      messenger role for NAADP in smooth muscle cells. 

PMID- 24882211
TI  - HDAC6 deacetylates and ubiquitinates MSH2 to maintain proper levels of MutSalpha.
AB  - MutS protein homolog 2 (MSH2) is a key DNA mismatch repair protein. It forms the
      MSH2-MSH6 (MutSalpha) and MSH2-MSH3 (MutSbeta) heterodimers, which help to ensure
      genomic integrity. MutSalpha not only recognizes and repairs mismatched
      nucleotides but also recognizes DNA adducts induced by DNA-damaging agents, and
      triggers cell-cycle arrest and apoptosis. Loss or depletion of MutSalpha from
      cells leads to microsatellite instability (MSI) and resistance to DNA damage.
      Although the level of MutSalpha can be reduced by the ubiquitin-proteasome
      pathway, the detailed mechanisms of this regulation remain elusive. Here we
      report that histone deacetylase 6 (HDAC6) sequentially deacetylates and
      ubiquitinates MSH2, leading to MSH2 degradation. In addition, HDAC6 significantly
      reduces cellular sensitivity to DNA-damaging agents and decreases cellular DNA
      mismatch repair activities by downregulation of MSH2. Overall, these findings
      reveal a mechanism by which proper levels of MutSalpha are maintained. 

PMID- 24882214
TI  - Belief in a just world is associated with activity in insula and somatosensory
      cortices as a response to the perception of norm violations.
AB  - Previous studies identified a network of brain regions involved in the perception
      of norm violations, including insula, anterior cingulate cortex (ACC), and right
      temporoparietal junction area (RTPJ). Activations in these regions are suggested
      to reflect the perception of norm violations and unfairness. The current study
      aimed to test this hypothesis by exploring whether a personal disposition to
      perceive the world as being just is related to neural responses to moral
      evaluations. The just-world-hypothesis describes a cognitive bias to believe in a
      just world in which everyone gets what he or she deserves and deserves what he or
      she gets. Since it has been demonstrated that ACC, RTPJ, and insula are involved
      in the perception of unfairness, we hypothesized that individual differences in
      the belief in a just world are reflected by different activations of these brain
      areas. Participants were confronted with scenarios describing norm-violating or 
      confirming behavior. FMRI results revealed an activation of dorsal ACC, RTPJ, and
      insula when perceiving norm violations, but only activity in insula/somatosensory
      cortex correlated with the belief in a just world. Thus, our results suggest a
      role for insula/somatosensory cortex for the belief in a just world. 

PMID- 24882215
TI  - Dopamine favors expansion of glucocorticoid-resistant IL-17-producing T cells in
      multiple sclerosis.
AB  - Dopamine (DA) is a neurotransmitter produced mainly in the central nervous system
      (CNS) that has immunomodulatory actions on T cells. As the multiple sclerosis
      (MS) has long been regarded as an autoimmune disease of CNS mediated by T cells,
      the objective of this study was to evaluate the impact of DA on in vitro
      functional status of T cells from relapsing-remitting (RR)-MS patients.
      Peripheral T-cells from RR-MS patients were activated by mitogens and cell
      proliferation and cytokine production were assayed by [(3)H]-thymidine uptake and
      ELISA, respectively. Our results demonstrated that DA enhanced in vitro T cell
      proliferation and Th17-related cytokines in MS-derived cell cultures. In
      addition, this catecholamine reduced Treg-related cytokines (IL-10 and TGF-beta)
      release by activated CD4(+) T cells. These DA-induced effects on T cells were
      mainly dependent on IL-6 production by both polyclonally-activated CD4(+) T cells
      and LPS-stimulated monocytes. Furthermore, the production of IL-17 and IL-6 by MS
      derived T cells was directly related with neurological disability (EDSS score),
      and the release of these cytokines was less sensitive to glucocorticoid
      inhibition in MS patients than in control group, mainly after DA addition. In
      conclusion, our data suggest that DA amplifies glucocorticoid-resistant Th17
      phenotype in MS patients, and this phenomenon could be, at least in part, due to
      its ability to induce IL-6 production by monocytes and CD4(+) T cells. 

PMID- 24882216
TI  - Traceable reference gas mixtures for sulfur-free natural gas odorants.
AB  - The first reference gas mixtures of sulfur-free natural gas odorants that are
      traceable to the International System of Units (SI) have been produced and their
      compositions validated. These mixtures, which contain methyl acrylate and ethyl
      acrylate at amount fractions between 1.1 and 2.1 MUmol mol(-1), can be used to
      underpin measurements of sulfur-free odorants, which are increasingly being used
      to odorize natural gas in transmission networks as they have less harmful
      properties than traditional sulfur-containing odorants. The reference gas
      mixtures produced have been shown to be stable in passivated aluminum cylinders
      for at least 8 months and have been validated (to within 6% or less) by
      interlaboratory measurements at three National Measurement Institutes. The
      stability of methyl acrylate and ethyl acrylate in gas sampling bags has been
      investigated, and the challenges of analyzing 2-ethyl-3-methylpyrazine, which is
      used as a stabilizer in sulfur-free odorants, are also briefly discussed. 

PMID- 24882219
TI  - A qualitative study of English community pharmacists' experiences of providing
      lifestyle advice to patients with cardiovascular disease.
AB  - BACKGROUND: Cardiovascular disease (CVD) progression is modifiable through
      lifestyle behaviors. Community pharmacists are ideally placed to facilitate self
      management of cardiovascular health however research shows varied pharmacist
      engagement in providing lifestyle advice. OBJECTIVE: This study explored
      community pharmacists' experiences and perceptions of providing lifestyle advice
      to patients with CVD. METHODS: Semi-structured interviews were conducted with
      fifteen pharmacists (1 supermarket; 7 multiple; 7 independent) recruited through
      multiple methods from community pharmacies across the Midlands, England. A
      thematic analysis was conducted using a Framework approach. RESULTS: Pharmacists
      categorized patients according to their perceptions of the patients' ability to
      benefit from advice. Many barriers to providing lifestyle advice were identified.
      Confidence to provide lifestyle advice varied, with pharmacists most comfortable
      providing lifestyle advice in conjunction with conversations about medicines.
      Some pharmacists felt lifestyle advice was an integral part of their role whilst
      others questioned whether pharmacists should give lifestyle advice at all,
      particularly when receiving no remuneration for doing so. CONCLUSION: Pharmacists
      viewed providing lifestyle advice as important but identified many barriers to
      doing so. Lifestyle advice provision was influenced by pharmacists' perceptions
      of patients. Professional identity and associated role conflict appeared to
      underpin many of the barriers to pharmacists providing lifestyle advice.
      Pharmacists may benefit from enhanced training to: increase their confidence to
      provide lifestyle advice; integrate lifestyle advice with regular pharmaceutical
      practice and challenge their perceptions of some patients' receptiveness to
      lifestyle advice and behavior change. Changes to the way UK pharmacists are
      remunerated may increase the provision of lifestyle advice.

PMID- 24882218
TI  - Unanchored K48-linked polyubiquitin synthesized by the E3-ubiquitin ligase TRIM6
      stimulates the interferon-IKKepsilon kinase-mediated antiviral response.
AB  - Type I interferons (IFN-I) are essential antiviral cytokines produced upon
      microbial infection. IFN-I elicits this activity through the upregulation of
      hundreds of IFN-I-stimulated genes (ISGs). The full breadth of ISG induction
      demands activation of a number of cellular factors including the IkappaB kinase
      epsilon (IKKepsilon). However, the mechanism of IKKepsilon activation upon IFN
      receptor signaling has remained elusive. Here we show that TRIM6, a member of the
      E3-ubiquitin ligase tripartite motif (TRIM) family of proteins, interacted with
      IKKepsilon and promoted induction of IKKepsilon-dependent ISGs. TRIM6 and the E2
      ubiquitin conjugase UbE2K cooperated in the synthesis of unanchored K48-linked
      polyubiquitin chains, which activated IKKepsilon for subsequent STAT1
      phosphorylation. Our work attributes a previously unrecognized activating role of
      K48-linked unanchored polyubiquitin chains in kinase activation and identifies
      the UbE2K-TRIM6-ubiquitin axis as critical for IFN signaling and antiviral
      response. 

PMID- 24882220
TI  - Cultural differences in human brain activity: a quantitative meta-analysis.
AB  - Psychologists have been trying to understand differences in cognition and
      behavior between East Asian and Western cultures within a single cognitive
      framework such as holistic versus analytic or interdependent versus independent
      processes. However, it remains unclear whether cultural differences in multiple
      psychological processes correspond to the same or different neural networks. We
      conducted a quantitative meta-analysis of 35 functional MRI studies to examine
      cultural differences in brain activity engaged in social and non-social
      processes. We showed that social cognitive processes are characterized by
      stronger activity in the dorsal medial prefrontal cortex, lateral frontal cortex
      and temporoparietal junction in East Asians but stronger activity in the anterior
      cingulate, ventral medial prefrontal cortex and bilateral insula in Westerners.
      Social affective processes are associated with stronger activity in the right
      dorsal lateral frontal cortex in East Asians but greater activity in the left
      insula and right temporal pole in Westerners. Non-social processes induce
      stronger activity in the left inferior parietal cortex, left middle occipital and
      left superior parietal cortex in East Asians but greater activations in the right
      lingual gyrus, right inferior parietal cortex and precuneus in Westerners. The
      results suggest that cultural differences in social and non-social processes are
      mediated by distinct neural networks. Moreover, East Asian cultures are
      associated with increased neural activity in the brain regions related to
      inference of others' mind and emotion regulation whereas Western cultures are
      associated with enhanced neural activity in the brain areas related to self
      relevance encoding and emotional responses during social cognitive/affective
      processes. 

PMID- 24882217
TI  - Innate host defense requires TFEB-mediated transcription of cytoprotective and
      antimicrobial genes.
AB  - Animal host defense against infection requires the expression of defense genes at
      the right place and the right time. Understanding such tight control of host
      defense requires the elucidation of the transcription factors involved. By using
      an unbiased approach in the model Caenorhabditis elegans, we discovered that HLH
      30 (known as TFEB in mammals) is a key transcription factor for host defense. HLH
      30 was activated shortly after Staphylococcus aureus infection, and drove the
      expression of close to 80% of the host response, including antimicrobial and
      autophagy genes that were essential for host tolerance of infection. TFEB was
      also rapidly activated in murine macrophages upon S. aureus infection and was
      required for proper transcriptional induction of several proinflammatory
      cytokines and chemokines. Thus, our data suggest that TFEB is a previously
      unappreciated, evolutionarily ancient transcription factor in the host response
      to infection. 

PMID- 24882222
TI  - The gearing function of running shoe longitudinal bending stiffness.
AB  - The purpose of the present study was to investigate whether altered longitudinal
      bending stiffness (LBS) levels of the midsole of a running shoe lead to a
      systematic change in lower extremity joint lever arms of the ground reaction
      force (GRF). Joint moments and GRF lever arms in the sagittal plane were
      determined from 19 male subjects running at 3.5 m/s using inverse dynamics
      procedures. LBS was manipulated using carbon fiber insoles of 1.9 mm and 3.2 mm
      thickness. Increasing LBS led to a significant shift of joint lever arms to a
      more anterior position. Effects were more pronounced at distal joints. Ankle
      joint moments were not significantly increased in the presence of higher GRF
      lever arms when averaged over all subjects. Still, two individual strategies (1:
      increase ankle joint moments while keeping push-off times almost constant, 2:
      decrease ankle joint moments and increase push-off times) could be identified in
      response to increased ankle joint lever arms that might reflect individual
      differences between subjects with respect to strength capacities or
      anthropometric characteristics. The results of the present study indicate that
      LBS systematically influences GRF lever arms of lower extremity joints during the
      push-off phase in running. Further, individual responses to altered LBS levels
      could be identified that could aid in finding optimum LBS values for a given
      individual.

PMID- 24882223
TI  - Structure sensitive chemical reactivity by palladium concave nanocubes and
      nanoflowers synthesised by a seed mediated procedure in aqueous medium.
AB  - Palladium nanocubes and their transformation to concave nanocubes and nanoflowers
      are realised by a seed mediated procedure in aqueous medium and at room
      temperature using cationic surfactants. The concave nanocubes and nanoflowers
      were found to be enclosed by high index facets. The under co-ordinated atoms
      present on the high index facets make these nanostructures chemically more active
      towards Suzuki coupling and Heck coupling reactions compared to the conventional
      nanocubes and spherical nanoparticles of similar size. 

PMID- 24882224
TI  - Spermbots: potential impact for drug delivery and assisted reproductive
      technologies.
AB  - Micromotors and nanomotors are an emerging research field that aims at achieving
      locomotion on the microscale for a variety of applications such as drug delivery,
      single cell manipulation, microsensors and lab-on-a-chip devices, just to point
      out a few. The enthusiastic development of hybrid micromotors harnessing
      biological power sources for physiologically compatible nano/microdevices has
      recently brought a lot of attention to the international research community that
      is looking for a solution for the actuation and locomotion on the microscale.
      This article describes the potential of sperm-driven micro-bio-robots in the
      biomedical field such as drug delivery or single cell manipulation. Herein, a
      specific potential of the sperm-driven micro-bio-robot is described that might
      have impact on the development of assisted reproductive technologies. 

PMID- 24882225
TI  - Impact of a culturally focused psychiatric consultation on depressive symptoms
      among Latinos in primary care.
AB  - OBJECTIVE: A culturally focused psychiatric (CFP) consultation service was
      implemented to increase engagement in mental health care and reduce depressive
      symptoms among adult Latino primary care patients. The aim of this study was to
      assess preliminary efficacy of the CFP consultation service to reduce depressive
      symptoms. METHODS: In a randomized controlled study, primary care clinics were
      randomly selected to provide either the two-session CFP intervention or enhanced
      usual care. For CFP intervention participants, study clinicians (psychologists or
      psychiatrists) provided a psychiatric assessment, psychoeducation, cognitive
      behavioral tools, and tailored treatment recommendations; primary care providers
      were provided a consultation summary. Depressive symptoms (as measured by the
      Quick Inventory of Depressive Symptomatology-Self Rated [QIDS-SR]) were assessed
      at baseline and six-month follow-up. Multiple regression analysis was conducted
      to evaluate whether CFP intervention participants showed greater improvement in
      depressive symptoms at follow-up, with control for baseline depression, clinic
      site, and significant covariates. RESULTS: Participants (N=118) were primarily
      Spanish-monolingual speakers (64%). Although depressive symptoms remained in the
      moderate range for both groups from baseline to six months, symptom reduction was
      greater among CFP intervention participants (mean+/-SD change in QIDS-SR
      score=3.46+/-5.48) than those in usual care (change=.09+/-4.43). The final
      multiple regression model indicated that participation in the CFP intervention
      predicted lower depressive symptoms at follow-up (unstandardized beta=-3.09,
      p=.008), independent of baseline depressive symptoms, clinic site, age, gender,
      and employment status. CONCLUSIONS: Results suggest that Latinos experiencing
      depressive symptoms may benefit from a short-term CFP consultation. Findings also
      support the integration of psychiatric interventions for Latinos in the primary
      care setting.

PMID- 24882227
TI  - [Usefulness of comparing of magnetic resonance imaging (MRI) findings prior to
      repeat biopsy and negative initial biopsy as a decision-making method for repeat
      prostate biopsy].
AB  - We retrospectively reviewed the data from a cohort of 44 patients with one
      initial negative transrectal ultrasound-guided prostate biopsy who underwent a
      repeat biopsy from 2006 to 2013. At each biopsy session, we checked patient age,
      serum prostate specific antigen (PSA), prostate volume, PSA density, PSA
      velocity, months from the initial biopsy session, multiparametric magnetic
      resonance imaging (MRI) findings (T2-weighted, dynamic contrast-enhanced and
      diffusion-weighted, 1.5 Tesla pelvic-phased array) prior to repeat biopsy and
      initial negative biopsy. Mean age was 68.2+/-8.82 years. PSA was 11.5+/-7.65
      ng/ml before repeat biopsy. Prostate cancer was detected in 15 (34.0%) patients
      at repeat biopsy. In univariate and multivariate analysis, positive MRI findings
      before repeat biopsy were significant independent predictors of a positive repeat
      biopsy. At per patient analysis, the sensitivity, specificity, positive and
      negative predictive values were 66.6, 68.9, 71.4 and 80.0% for MRI before repeat
      biopsy. No suspicious lesion on MRI before repeat biopsy was relevant to negative
      biopsy. According to the comparison of MRI findings prior to repeat biopsy and
      negative initial biopsy, suspicious MRI findings at the peripheral zone before
      repeat biopsy and initial negative biopsy were relevant to a high cancer
      detection rate (83.3%) at repeat prostate biopsy. These results suggested that
      the absence of a suspicious lesion on MRI before repeat biopsy could guide the
      avoidance of repeat biopsy and suspicious MRI findings at the peripheral zone
      before repeat biopsy and initial negative biopsy could guide repeat biopsy. 

PMID- 24882228
TI  - [A case of complete disappearance of paraneoplestic syndrome after curative
      resection of bone metastasis in renal cell carcinoma].
AB  - A case of renal cell carcinoma presenting with paraneoplastic syndrome is
      reported. A 69-year-old man with uncontrolled diabetes was incidentally found to
      have a left thoracic tumor and a right renal tumor. He had intermittent fever of
      39C or more and laboratory data showed diabetes and high C-reactive protein
      level. A radical nephrectomy was performed, but the neoplastic syndrome did not
      improve. After a second surgery consisting of complete resection of solitary bone
      metastasis the symptoms resolved immediately. At 6 months postoperatively, he had
      no reoccurence. Generally prognosis of patients with bone metastasis from renal
      cell carcinoma has been said to be poor, but surgical control of bone metastasis
      may be a key factor for the prognosis of patient with metastatic RCC in the era
      of targeted therapy.

PMID- 24882229
TI  - [Intrarenal Bacillus Calmette-Guerin perfusion therapy was effective for
      carcinoma in situ of the upper urinary tract after ileal conduit replacement : a
      case report].
AB  - A 63-year-old man who had undergone radical cystectomy and ileal conduit
      formation for invasive bladder cancer 3 years before presented with continuous
      positive urinary cytology in the ileal conduit. His diagnosis was carcinoma in
      situ (CIS) of the left upper urinary tract. He was treated with Bacillus Calmette
      Guerin (BCG) perfusion therapy using a single-J ureteric stent. BCG (80 mg) in
      100 ml saline was instilled in a one-hour period weekly for 6 weeks. Usage of
      another catheter was effective for continuing the therapy. Urinary cytology in
      the left upper urinary tract and the ileal conduit became negative after the
      therapy. There was no evidence of recurrence or metastasis of urothelial
      carcinoma 6 months after the therapy. 

PMID- 24882221
TI  - Effects of elevated carbon dioxide, elevated temperature, and rice growth stage
      on the community structure of rice root-associated bacteria.
AB  - The effects of free-air carbon dioxide enrichment (FACE) and elevated soil and
      water temperature (warming) on the rice root-associated bacterial community were
      evaluated by clone library analysis of the 16S ribosomal RNA gene. Roots were
      sampled at the panicle initiation and ripening stages 41 and 92 days after
      transplanting (DAT), respectively. The relative abundances of the methanotrophs
      Methylosinus and Methylocystis were increased by warming and decreased by FACE at
      92 DAT, which indicated that microbial methane (CH4) oxidation in rice roots may
      have been influenced by global warming. The relative abundance of Burkholderia
      kururiensis was increased by warming at 41 DAT and by FACE or warming at 92 DAT.
      The abundances of methanotrophs increased during rice growth, which was likely
      induced by an enhancement in the emission of CH4 from the paddy fields,
      suggesting that CH4 is one of the predominant factors affecting the structure of
      the microbial community in rice roots. Marked variations in the community
      structure were also observed during rice growth in other genera: Bradyrhizobium,
      Clostridium, and an unknown genus close to Epsilonproteobacteria were abundant at
      92 DAT, whereas Achromobacter was abundant at 41 DAT. These results demonstrated
      that the community structures of rice root-associated bacteria were markedly
      affected by FACE, temperature, and the rice growth stage. 

PMID- 24882226
TI  - Emerging technologies for monitoring drug-resistant tuberculosis at the point-of
      care.
AB  - Infectious diseases are the leading cause of death worldwide. Among them,
      tuberculosis (TB) remains a major threat to public health, exacerbated by the
      emergence of multiple drug-resistant (MDR) and extensively drug-resistant (XDR)
      Mycobacterium tuberculosis (Mtb). MDR-Mtb strains are resistant to first-line
      anti-TB drugs such as isoniazid and rifampicin; whereas XDR-Mtb strains are
      resistant to additional drugs including at least to any fluoroquinolone and one
      of the second-line anti-TB injectable drugs such as kanamycin, capreomycin, or
      amikacin. Clinically, these strains have significantly impacted the management of
      TB in high-incidence developing countries, where systemic surveillance of TB drug
      resistance is lacking. For effective management of TB on-site, early detection of
      drug resistance is critical to initiate treatment, to reduce mortality, and to
      thwart drug-resistant TB transmission. In this review, we discuss the diagnostic
      challenges to detect drug-resistant TB at the point-of-care (POC). Moreover, we
      present the latest advances in nano/microscale technologies that can potentially
      detect TB drug resistance to improve on-site patient care. 

PMID- 24882230
TI  - [A case of effective neoadjuvant chemotherapy (MVEC) against right ureteral
      cancer involving bladder (cT4N1M0)].
AB  - Poorly differentiated ureteral cancer has a poor prognosis, and tumor recurrence
      is frequent even after nephroureterectomy. We performed neoadjuvant chemotherapy
      to prevent postoperative recurrence. A 74-year-old man was diagnosed with
      ureteral cancer (3 cm) by magnetic resonance imaging (MRI). The clinical stage
      was T4N1M0. Histological examination by transurethral biopsy revealed an
      urothelial carcinoma, G3, pT1. After a month, the tumor size increased from 3.0
      cm to 4.0 cm. With two cycles of neoadjuvant chemotherapy consisting of
      methotrexate, vinblastine, epirubicin and cisplatin (MVEC) partial remission
      (regression rate : 87%) was achieved, Following MVEC, right retroperitoneoscopy
      assisted nephroureterectomy, total cystectomy, and ileal conduit were performed.
      Pathological stage was pT0. After two years, postoperative recurrence has not
      appeared. 

PMID- 24882231
TI  - [Modified BEP regimen leads to abatement of choriocarcinoma syndrome in a patient
      with extra gonadal germ cell tumor : a case report].
AB  - We present a case study of a 46-year-old man with extra gonadal germ cell tumor
      with multiple lung metastases and very high levels (324,100 mIU/ml) of the tumor
      marker human chorionic gonadotropin (hCG). He underwent chemotherapy with VP-16,
      ifosfamide and cisplatinum regimen, but on day 2, he noticed strong dyspnea. A
      chest X-ray showed bilateral infiltration of the lungs, and he was diagnosed with
      acute respiratory distress syndrome (ARDS) from choriocarcinoma syndrome. After
      ARDS improved, he underwent modified bleomycin, VP-16 and cisplatinum for
      induction therapy again. After salvage chemotherapies, levels of the tumor marker
      hCG decreased to normal levels, and retroperitoneal lymph node dissection and
      left lung wedge resection were performed to confirm pathological complete
      remission. No obvious recurrence, as shown by tumor markers and imaging studies,
      has been observed for 17 months after the treatments. 

PMID- 24882232
TI  - [A case of tethered cord syndrome in an elderly man].
AB  - A 71-year-old man had been under treatment for nocturia with an anti-cholinergic
      agent at a urologic clinic for the last 2 years. Because the symptoms did not
      improve, he was referred to our hospital for treatment of urinary retention.
      Based on the findings of a neurological examination, we suspected the presence of
      a neurogenic bladder due to sacral lesions. Moreover, magnetic resonance imaging
      indicated tethered cord syndrome (TCS) due to spinal cord lipoma. He underwent
      surgical treatment for TCS, which improved storage function, but not voiding
      function. Generally speaking, we believe that early diagnosis of TCS facilitates
      early surgery that can prevent the development of neurogenic disorders. In the
      present case, if the neurological findings had been appropriately assessed and
      cystometry/urodynamic studies had been performed at an earlier stage, a prompt
      diagnosis could have been made and surgery could have been performed earlier as
      well. Although adult cases with TCS are rarely observed, TCS should be considered
      as one of the causes of intractable lower urinary tract symptoms. 

PMID- 24882233
TI  - Photochemical generation of strong one-electron reductants via light-induced
      electron transfer with reversible donors followed by cross reaction with
      sacrificial donors.
AB  - This work illustrates a modified approach for employing photoinduced electron
      transfer reactions coupled to secondary irreversible electron transfer processes
      for the generation of strongly reducing equivalents in solution. Through
      irradiation of [Ru(LL)3](2+) (LL= diimine ligands) with tritolylamine (TTA) as
      quencher and various alkyl amines as sacrificial electron donors, yields in
      excess of 50% can be achieved for generation of reductants with E(0)(2+/1+)
      values between -1.0 and -1.2 V vs NHE. The key to the system is the fact that the
      TTA cation radical, formed in high yield in reaction with the photoexcited
      [Ru(LL)3](2+) complex, reacts irreversibly with various sacrificial electron
      donating amines that are kinetically unable to directly react with the
      photoexcited complex. The electron transfer between the TTA(+) and the
      sacrificial amine is an energetically uphill process. Kinetic analysis of these
      parallel competing reactions, consisting of bimolecular and pseudo first-order
      reactions, allows determination of electron transfer rate constants for the cross
      electron transfer reaction between the sacrificial donor and the TTA(+). A
      variety of amines were examined as potential sacrificial electron donors, and it
      was found that tertiary 1,2-diamines are most efficient among these amines for
      trapping the intermediate TTA(+). This electron-donating combination is capable
      of supplying a persistent reducing flux of electrons to catalysts used for
      hydrogen production. 

PMID- 24882234
TI  - Immunisation coverage annual report, 2011.
AB  - This, the 5th annual immunisation coverage report, documents trends during 2011
      for a range of standard measures derived from Australian Childhood Immunisation
      Register data, and National Human Papillomavirus (HPV) Vaccination Program
      Register data. The proportion of children 'fully vaccinated' at 12, 24 and 60
      months of age was 91.4%, 92.2% and 89.5% respectively. Although pneumococcal
      vaccine had similar coverage at 12 months to other vaccines, coverage was lower
      for rotavirus at 12 months (83.8%) and varicella at 24 months (83.9%). By late
      2011, the percentage of children who received the 1st dose of DTPa vaccine dose
      at less than 8 weeks of age was greater than 50% in 3 jurisdictions, the
      Australian Capital Territory, Victoria, and Queensland and at 70% for New South
      Wales and Tasmania. Although coverage at 12 months of age was lower among
      Indigenous children than non-Indigenous children in all jurisdictions, the extent
      of the difference varied. Overall, coverage at 24 months of age exceeded that at
      12 months of age nationally. At 60 months of age, there was dramatic variation
      between individual jurisdictions, ranging from coverage 8% lower in Indigenous
      children in South Australia to 6% higher in the Northern Territory. As previously
      documented, vaccines recommended for Indigenous children only (hepatitis A and
      pneumococcal polysaccharide vaccine) had suboptimal coverage at 60% and 68%,
      respectively. On-time receipt (before 49 months of age) of vaccines by Indigenous
      children at the 60-month milestone age improved between 2010 (18%) and 2011 (19%)
      but the disparity in on-time vaccination between Indigenous and non-Indigenous
      children increased at all 3 age milestones. The percentage of vaccine objectors
      in 2011 (1.7%) has increased from 2007 when it was 1.1%. Coverage data for the
      3rd dose of HPV from the national HPV register in the school catch up program was
      71% but was substantially lower for the catch-up program for women outside school
      (39%-67%), although this was an improvement from 2010.

PMID- 24882235
TI  - Australia's notifiable disease status, 2011: annual report of the National
      Notifiable Diseases Surveillance System.
AB  - In 2011, 65 diseases and conditions were nationally notifiable in Australia.
      States and territories reported a total of 238,158 notifications of communicable
      diseases to the National Notifiable Diseases Surveillance System, an increase of
      14% on the number of notifications in 2010. This increase was largely due to the
      ongoing pertussis epidemic and higher than usual inter-season notifications of
      influenza. In 2011, the most frequently notified diseases were sexually
      transmissible infections (95,456 notifications, 40.1% of total notifications),
      vaccine preventable diseases (81,872 notifications, 34.4% of total
      notifications), and gastrointestinal diseases (32,784 notifications, 13.8% of
      total notifications). There were 17,123 notifications of bloodborne diseases;
      8,306 notifications of vectorborne diseases; 1,928 notifications of other
      bacterial infections; 681 notifications of zoonoses and 8 notifications of
      quarantinable diseases.

PMID- 24882236
TI  - Australian Paediatric Surveillance Unit annual report, 2012.

PMID- 24882237
TI  - Flutracking weekly online community survey of influenza-like illness annual
      report 2011 and 2012.
AB  - Flutracking is a national online community influenza-like illness (ILI)
      surveillance system that monitors weekly ILI activity and field vaccine
      effectiveness (FVE). This article reports on the 2011 and 2012 findings from
      Flutracking. There was a 22% increase in participants to 16,046 who completed at
      least one survey in 2012, compared with 2011 (13,101). By October 2012 (the end
      of the 2012 season), 54.2% of participants had received the 2012 seasonal
      vaccine, while by the end of the 2011 season, 55.9% of participants had received
      the 2011 seasonal vaccine. From 2007 to 2012 the FVE calculation for New South
      Wales participants demonstrated that the seasonal vaccine was effective except in
      2009 when a novel H1N1 virus was dominant. The 2012 Flutracking ILI weekly
      incidence peaked in mid-July at 4.9% in the unvaccinated group, 1 month earlier
      than laboratory confirmed influenza. The 2011 Flutracking ILI weekly incidence
      peaked in mid-August at 4.1% in the unvaccinated group, 1 week later than
      laboratory confirmed influenza. Similar to laboratory notifications, there was an
      increase in ILI activity from 2010 to 2012, with the peak weekly ILI prevalence
      for 2012 Flutracking data, (unstratified by vaccination status), being higher
      (4.7%) than the peak weekly prevalence for 2011 (3.8%) and 2010 (3.7%). The 2012
      Flutracking influenza season showed moderate levels of ILI, compared with lower
      levels of ILI seen in 2011 and 2010, and consistent with the increase in national
      influenza laboratory notifications.

PMID- 24882238
TI  - Epidemiology of sexually transmissible infections in New South Wales: are case
      notifications enough?
AB  - BACKGROUND: Surveillance of sexually transmissible infections (STI)s is important
      to assess the disease burden in the population and to monitor and evaluate
      changes in trends over time. Routinely collected surveillance data in New South
      Wales are reliant on case reporting, which for many infections is an inadequate
      mechanism for capturing incidence and prevalence. Increasing rates of chlamydia
      over the past decade have sparked intense debate as to whether the current
      notification system is optimal and whether the true burden of infection are being
      measured. This study describes the current surveillance for STIs in New South
      Wales. METHODS: New South Wales-specific data for the years 2000-2009 were
      analysed. Notification data were used to examine the rate of the 4 STIs that are
      notifiable in New South Wales; chlamydia, gonorrhoea, infectious syphilis and HIV
      notifications. Hospital admissions and chlamydia-associated pelvic inflammatory
      disease were analysed using admitted patient data. RESULTS: Chlamydia was the
      most frequently reported of the notifiable STIs in New South Wales. Despite the
      higher rates of notification compared with other STIs, chlamydia-related
      hospitalisations contribute less than a 5th of all STI-related hospital
      admissions. Infectious syphilis contributed to the highest proportion of all STI
      related hospitalisations in New South Wales and rates increased from 2000 to
      2009. For other STIs such as anogenital herpes and gonorrhoea, hospital
      admissions remained stable for the same period. CONCLUSIONS: Notifications data
      for STIs should be complemented with hospital admission and other data sources to
      better describe STI morbidity. A synthesis of these data sources is needed to
      improve current surveillance and allow for better comparisons and trend analysis
      of STIs in New South Wales.

PMID- 24882239
TI  - Revised surveillance case definitions.

PMID- 24882240
TI  - OzFoodNet quarterly report, 1 October to 31 December 2012.

PMID- 24882241
TI  - National notifiable diseases surveillance system, 1 July to 30 september 2013.

PMID- 24882242
TI  - Australian childhood immunisation coverage, 1 January to 31 March cohort,
      assessed as at 30 June 2013.

PMID- 24882243
TI  - Australian Gonococcal Surveillance Programme, 1 July to 30 September 2013.

PMID- 24882244
TI  - Australian Meningococcal Surveillance Programme, 1 July to 30 September 2013.

PMID- 24882245
TI  - Australian Sentinel Practices Research Network, 1 October to 31 December 2012.

PMID- 24882246
TI  - HIV and AIDS surveillance, 1 April to 30 June 2012.

PMID- 24882247
TI  - HIV and AIDS surveillance, 1 July to 30 September 2012.

PMID- 24882248
TI  - HIV and AIDS surveillance, 1 October to 31 December 2012.

PMID- 24882250
TI  - Antiviral C-25 epimers of 26-acetoxy steroids from the South China Sea gorgonian
      Echinogorgia rebekka.
AB  - Four new steroids with an acetoxy linked at the end of the side chain,
      echrebsteroids A-D (1-4) were obtained from the South China Sea gorgonian
      Echinogorgia rebekka. The absolute configurations of 1-3 were determined using
      the modified Mosher's method on the hydrolysis products. The isolation of the
      pair of epimers (2 and 3) represents the first reported separation of C-25
      epimers of 26-acetoxy steroids. The (25R)-epimer (3) exhibited promising
      antiviral activity against respiratory syncytial virus with an IC50 value of 0.19
      MUM and a comparatively higher therapeutic ratio (TC50/IC50 = 128). 

PMID- 24882249
TI  - Invasive pneumococcal disease surveillance Australia, 1 July to 30 September
      2013.

PMID- 24882251
TI  - Surface Gibbs energy interaction of phospholipid/cholesterol monolayers deposited
      on mica with probe liquids.
AB  - The mica supported binary monolayers containing phospholipids: 1,2-dipalmitoyl-sn
      glycero-3-phosphocholine (DPPC), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC),
      2-oleoyl-1-palmitoyl-sn-glycero-3-phosphocholine (POPC), 1,2-dipalmitoyl-sn
      glycero-3-phospho-rac-(1-glycerol) (DPPG), and cholesterol (Chol), mixed at
      different molar fractions, were investigated by measurements of the contact
      angles of water, formamide and diiodomethane. This allowed calculation of
      apparent surface Gibbs energy (further in the paper termed as 'surface free
      energy') of the monolayers according to the theoretical approach developed by
      Chibowski (contact angle hysteresis model, CAH). Then, based on the surface free
      energy values, the molar interaction Gibbs energy of the lipid molecules with the
      given probe liquid was evaluated. These values correlate with the values of
      excess area, interpreted as an indicator of the condensing effect of cholesterol
      on phospholipid monolayers at the air-water interface. The results indicate that
      the thermodynamic parameters of interactions depend on the monolayer composition
      and the probe liquid used to their determination. Changes of the parameters are
      discussed in relation to the monolayer packing, ordering, tilting of the
      molecules, and properties of the probe liquids as well. 

PMID- 24882252
TI  - Nonalcoholic fatty liver disease among potential live liver donors--a preliminary
      experience from Sri Lanka.

PMID- 24882253
TI  - Novel multimetabolite prediction of walnut consumption by a urinary biomarker
      model in a free-living population: the PREDIMED study.
AB  - The beneficial impact of walnuts on human health has been attributed to their
      unique chemical composition. In order to characterize the dietary walnut
      fingerprinting, spot urine samples from two sets of 195 (training) and 186
      (validation) individuals were analyzed by an HPLC-q-ToF-MS untargeted
      metabolomics approach, selecting the most discriminating metabolites by
      multivariate data analysis (VIP >= 1.5). Stepwise logistic regression analysis
      was used to design a multimetabolite prediction biomarker model. The global
      performance of the model and each included metabolite in it was evaluated by
      receiver operating characteristic curves, using the area under the curve (AUC)
      values. Dietary exposure to walnuts was characterized by 18 metabolites,
      including markers of fatty acid metabolism, ellagitannin-derived microbial
      compounds, and intermediate metabolites of the tryptophan/serotonin pathway. The
      predictive model of walnut exposure included at least one compound of each class.
      The AUC (95% CI) for the combined biomarker model was 93.4% (90.1-96.8%) in the
      training set and 90.2% (85.9-94.6%) in the validation set. The AUCs for
      individual metabolites were <=85%. As far as we know, this is the first study
      proposing a combination of biomarkers of walnut exposure in a population under
      free-living conditions, as considered in epidemiological studies examining
      associations between diet and health outcomes. 

PMID- 24882254
TI  - Factors associated with early reinduction chemotherapy for adults with acute
      myeloid leukemia.

PMID- 24882255
TI  - Multiparameter flow cytometry in the differential diagnosis of aberrant T-cell
      clones of unclear significance.
AB  - Immunophenotypic distinction between neoplastic and reactive T-cell clones can be
      challenging, as peripheral T-cell lymphomas (PTCLs) lack an immunophenotypic
      marker of clonality. Systematic screening of 10,510 cases analyzed by
      immunophenotyping at our institution between 2006 and 2012 resulted in 49 cases
      with aberrant T-cell populations of unclear significance. Review of patient
      charts allowed us to assign these cases to three categories. In 21 cases, PTCL
      could later be confirmed by complementary diagnostics (PTCL group). In 20 cases,
      follow-up confirmed the reactive nature of the aberrant T-cells (non-PTCL group).
      Eight cases remained of unclear significance. Neither the population size nor the
      number of aberrant markers differed significantly between the PTCL and non-PTCL
      groups. Only loss of CD7 was found significantly more often in patients with PTCL
      than in patients with non-PTCL (p = 0.037). Our data show that aberrant T-cell
      populations need to be interpreted in the clinicopathological context, as
      reactive and neoplastic phenotypes largely overlap.

PMID- 24882256
TI  - Toxoplasmosis in patients with hematologic malignancies.

PMID- 24882257
TI  - Development of T-cell lymphomas with an activated cytotoxic immunophenotype,
      including anaplastic large cell lymphomas, in patients with chronic lymphocytic
      leukemia: a series of six cases.

PMID- 24882258
TI  - High levels of CD160 expression up-regulated counts of chronic lymphocytic
      leukemia cells and were associated with other clinical parameters in Chinese
      patients with chronic lymphocytic leukemia.

PMID- 24882259
TI  - Short-term cardiac toxicity of autologous hematopoietic stem cell transplant for
      multiple myeloma.

PMID- 24882260
TI  - When indolent follicular lymphoma is not indolent.

PMID- 24882261
TI  - Shelf-life extension of azacitidine: waste and cost reduction in the treatment of
      myelodysplastic syndromes.

PMID- 24882263
TI  - High rate of both hematopoietic and solid tumors associated with large granular
      lymphocyte leukemia.

PMID- 24882262
TI  - Toxicity and efficacy of intrathecal liposomal cytarabine in children with
      leukemia/lymphoma relapsing in the central nervous system: a retrospective
      multicenter study.
AB  - The toxicity and efficacy of intrathecal liposomal cytarabine (LC) were evaluated
      in children with central nervous system (CNS) relapsed/refractory acute
      leukemia/lymphoma. Thirty patients (male:female ratio 21:9; median age 9.4 years)
      with CNS relapsed/resistant disease were treated with intrathecal LC at dosages
      adjusted for age. Twenty-seven (90%) patients simultaneously received systemic
      chemotherapy, including concurrent high-dose cytarabine or methotrexate in 21
      (70%) cases. Of 28 patients evaluable for response, 25 patients (89%) achieved
      CNS complete remission and three (11%) partial remission. The median number of
      intrathecal LC administrations per patient was 4. The cerebrospinal fluid was
      cleared after a median of 3 intrathecal LC administrations. Neurological toxicity
      >= grade 3 occurred in four (13%) patients. No permanent sequelae were observed.
      The median overall survival was 20.9 months and the 5-year probability of
      survival was 46%. These encouraging data suggest that intrathecal LC is well
      tolerated and effective in children with relapsed/refractory CNS
      leukemia/lymphoma. 

PMID- 24882264
TI  - What is the optimal dose of high-dose methotrexate in the initial treatment of
      primary central nervous system lymphoma?

PMID- 24882265
TI  - Block copolymer assembly on nanoscale patterns of polymer brushes formed by
      electrohydrodynamic jet printing.
AB  - Fundamental understanding of the self-assembly of domains in block copolymers
      (BCPs) and capabilities in control of these processes are important for their use
      as nanoscale templates in various applications. This paper focuses on the self
      assembly of spin-cast and printed poly(styrene-block-methyl methacrylate) BCPs on
      patterned surface wetting layers formed by electrohydrodynamic jet printing of
      random copolymer brushes. Here, end-grafted brushes that present groups of
      styrene and methyl methacrylate in geometries with nanoscale resolution
      deterministically define the morphologies of BCP nanostructures. The materials
      and methods can also be integrated with lithographically defined templates for
      directed self-assembly of BCPs at multiple length scales. The results provide not
      only engineering routes to controlled formation of complex patterns but also
      vehicles for experimental and simulation studies of the effects of chemical
      transitions on the processes of self-assembly. In particular, we show that the
      methodology developed here provides the means to explore exotic phenomena
      displayed by the wetting behavior of BCPs, where 3-D soft confinement, chain
      elasticity, interfacial energies, and substrate's surface energy cooperate to
      yield nonclassical wetting behavior. 

PMID- 24882267
TI  - Multicolor tunable luminescence and paramagnetic properties of NaGdF4:Tb3+/Sm3+
      multifunctional nanomaterials.
AB  - Tb(3+) and/or Sm(3+) doped NaGdF4 luminescent nanomaterials have been
      successfully synthesized by an SDS-assisted one-step hydrothermal method. The
      samples were characterized by X-ray diffraction (XRD), field-emission scanning
      electron microscope (FE-SEM), transmission electron microscope (TEM), X-ray
      energy dispersive spectrometer (EDS), photoluminescence (PL) spectra and a
      vibrating sample magnetometer (VSM). The results show that the synthesized
      samples are all pure beta-NaGdF4. The as-prepared Tb(3+) or Sm(3+) doped samples
      show strong green and yellow emission, originating from the allowed (5)D3
      >(7)F(J) (J = 5, 4, 3, 2) and (5)D4->(7)F(J) (J = 6, 5, 4, 3) transitions of the
      Tb(3+) ions and the (4)G(5/2)->(6)H(5/2), (6)H(7/2), (6)H(9/2) transition of the
      Sm(3+) ions. Based on the excitation wavelengths, multiple (yellowish green,
      yellow, white) emissions are obtained by Sm(3+) ion co-activated NaGdF4:Tb(3+)
      phosphors. Moreover, an energy transfer from Tb(3+) to Sm(3+) is observed, which
      is justified through the luminescence spectra and the fluorescence decay curves.
      Furthermore, the resonance-type energy transfer from Tb(3+) to Sm(3+) is
      demonstrated to occur via the dipole-dipole mechanism. In addition, the obtained
      samples also exhibit paramagnetic properties at room temperature. It is obvious
      that these multifunctional Tb(3+), Sm(3+) co-doped beta-NaGdF4 nanomaterials,
      with tunable multicolors and intrinsic paramagnetic properties, may have
      potential application in the fields of full-color displays, biological labels,
      bioseparation and magnetic resonance imaging.

PMID- 24882268
TI  - Statins and osteoporosis: a latent promise.

PMID- 24882266
TI  - Human cytochrome P450 epoxygenases: variability in expression and role in
      inflammation-related disorders.
AB  - Beyond their contribution to the metabolism of xenobiotics, cytochrome P450 (CYP)
      epoxygenases are actively involved in the metabolism of endogenous substances,
      like arachidonic acid (AA). The main human CYP epoxygenases, i.e. CYP2C8, CYP2C9,
      CYP2C19 and CYP2J2, convert AA to four regioisomer epoxyeicosatrienoic acids
      (EETs). EETs possess a wide range of established protective effects on the human
      cardiovascular system of which anti-inflammatory actions have gained great recent
      interest. The expression of CYP epoxygenases is regulated through an extremely
      complex network of nuclear receptors, microRNAs and genetic/epigenetic factors.
      Accordingly, a large number of biological variables as well as xenobiotics and
      environmental factors can influence the expression of CYP epoxygenases, resulting
      in a significant intra- and inter-individual variability in the expression and
      activity of these enzymes and subsequently in EET biosynthesis. Moreover, human
      CYP epoxygenases are mainly expressed in the liver; however, these enzymes are
      also expressed, at various extents, in most extrahepatic tissues, resulting in a
      marked inter-tissue variability in the expression of CYP epoxygenases. The inter
      tissue, inter- and intra-individual variability in the expression of epoxygenases
      may lead to differences in the relative abundance of EETs among tissues, among
      individuals of a population and/or different ethnicities and in a given
      individual under various conditions. The variation in the abundance of EETs may
      explain, at least in part, the inter-tissue and inter-individual differences
      observed in the prevalence of inflammation-related disorders including
      cardiovascular disease, and why in a given individual, various conditions can
      contribute to the development of diseases with an important inflammatory
      component. 

PMID- 24882269
TI  - Kinetic method for the large-scale analysis of the binding mechanism of histone
      deacetylase inhibitors.
AB  - Performing kinetic studies on protein ligand interactions provides important
      information on complex formation and dissociation. Beside kinetic parameters such
      as association rates and residence times, kinetic experiments also reveal
      insights into reaction mechanisms. Exploiting intrinsic tryptophan fluorescence a
      parallelized high-throughput Forster resonance energy transfer (FRET)-based
      reporter displacement assay with very low protein consumption was developed to
      enable the large-scale kinetic characterization of the binding of ligands to
      recombinant human histone deacetylases (HDACs) and a bacterial histone
      deacetylase-like amidohydrolase (HDAH) from Bordetella/Alcaligenes. For the
      binding of trichostatin A (TSA), suberoylanilide hydroxamic acid (SAHA), and two
      other SAHA derivatives to HDAH, two different modes of action, simple one-step
      binding and a two-step mechanism comprising initial binding and induced fit, were
      verified. In contrast to HDAH, all compounds bound to human HDAC1, HDAC6, and
      HDAC8 through a two-step mechanism. A quantitative view on the inhibitor-HDAC
      systems revealed two types of interaction, fast binding and slow dissociation. We
      provide arguments for the thesis that the relationship between quantitative
      kinetic and mechanistic information and chemical structures of compounds will
      serve as a valuable tool for drug optimization. 

PMID- 24882270
TI  - Exploring host-guest interactions of sulfobutylether-beta-cyclodextrin and
      phenolic acids by chemiluminescence and site-directed molecular docking.
AB  - We have developed a rapid method that allows us to characterize the binding
      interaction of sulfobutylether-beta-cyclodextrin (SBE-beta-CD) with five
      therapeutically important phenolic acids: ferulic acid, caffeic acid, gallic
      acid, protocatechuic acid, and vanillic acid. The method utilizes a flow
      injection chemiluminescence (FI-CL) technique that relies on the inhibition of a
      cyclodextrin-luminol chemiluminescence (CL) by increasing amounts of the phenolic
      acids (PAs). This loss of CL with increasing amounts of PAs fits the equation
      lg[(I0-Is)/Is]=lgKPAs+nlg[PAs], allowing calculation of the binding constant
      (KPAs) and stoichiometric ratio (n). The five phenolic acids and SBE-beta-CD
      formed complexes with a stoichiometric ratio of 1:1. The binding constants were
      on the order of 10(7) M(-1). These results showed a good correlation with the
      scores calculated by molecular docking. Further investigation by site-directed
      molecular docking and linear correlation analysis revealed that PAs entered the
      larger cavity of SBE-beta-CD and the formation constants mainly depended on the
      number of hydrogen bond acceptors in the PAs structures. All these results
      indicate that the CL-based affinity method can be used for direct determination
      of host-guest inclusion interactions and has great potential to become a reliable
      alternative for quantitatively studying host-guest binding and drug-protein
      interactions.

PMID- 24882271
TI  - Inhaled liposomal amikacin.
AB  - ArikaceTM is a novel formulation of inhaled liposomal amikacin that can penetrate
      deep within airway secretions and within Pseudomonas aeruginosa biofilms, making
      it an attractive therapeutic option for the treatment of cystic fibrosis (CF)
      pulmonary infections. Initial Phase I and Phase II studies in CF patients with
      chronic P. aeruginosa infection demonstrated that ArikaceTM was a safe drug that
      resulted in significant improvements in lung function after 14-28 days of
      treatment. Phase III studies of inhaled liposomal amikacin compared to tobramycin
      inhalation solution in CF patients with P. aeruginosa infection revealed a
      comparable increase in forced expiratory volume in 1 second at the end of three
      cycles. In addition, inhaled liposomal amikacin has other potential applications
      in the management of difficult-to-treat pulmonary infections. A Phase II trial is
      currently underway to study the use of ArikaceTM for the treatment of
      recalcitrant nontuberculous mycobacterial lung disease. 

PMID- 24882273
TI  - Role of ABO blood group and of other risk factors on the presence of residual
      vein obstruction after deep-vein thrombosis.
AB  - The presence of residual vein obstruction (RVO) has been consistently associated
      with an increased risk of post-thrombotic syndrome in patients with a previous
      deep vein thrombosis (DVT) and there is some evidence suggesting an increased
      risk of DVT recurrence. Only few studies have assessed potential risk factors for
      RVO. In this study, we evaluated whether ABO blood group with or without
      associated thrombophilic abnormalities is associated with RVO after a standard
      course of anticoagulation for a first DVT. Patients with a first DVT who
      underwent screening for thrombophilic abnormalities were eligible for this study.
      Information was collected on ABO blood group and on risk factors for DVT. Each
      patient underwent compression ultrasonography of the lower limbs for the
      detection of RVO at least 6months after a standard course of anticoagulant
      treatment. A total of 268 patients (mean age 50.3years, 120 women) were included.
      After 8.3+/-2.9months of anticoagulant treatment, 126 (47.0%) patients had RVO.
      At multivariate analysis, active malignancy (Odds Ratios [OR] 5.54, 95%
      confidence interval [CI] 2.17, 14.13), non-O blood group (OR 3.71, 95% CI 1.61,
      8.56), and femoral involvement (OR 3.35 95% CI 1.94, 5.78) were significantly
      associated with RVO whereas an unprovoked index event was only marginally
      significant (OR 1.81 95% CI 0.98, 3.36 p 0.06) and severe thrombophilia was not
      associated with RVO (OR 1.32 95% CI 0.56, 3.11). After a standard course of
      anticoagulation for a first DVT, patients with non-O blood group are at increased
      risk of RVO. 

PMID- 24882272
TI  - Dasatinib enhances migration of monocyte-derived dendritic cells by reducing
      phosphorylation of inhibitory immune receptors Siglec-9 and Siglec-3.
AB  - The SRC family of kinases (SFKs) is crucial to malignant growth, but also
      important for signaling in immune cells such as dendritic cells (DCs). These
      specialized antigen-presenting cells are essential for inducing and boosting
      specific T-cell responses against pathogens and malignancies. Targeted therapy
      with SFK inhibitors holds great promise as a direct anti-cancer treatment, but
      potentially also as an indirect treatment via immunomodulation. Here, we
      investigated whether the BCR-ABL/SRC inhibitor dasatinib would modulate the major
      effector functions of DCs, especially their migration, a prerequisite to
      interaction with lymphocytes in secondary lymphoid organs. We report for the
      first time that dasatinib more than doubled the number of mature human monocyte
      derived DCs (moDCs) migrating toward a CCL19 gradient despite unchanged CCR7
      expression when used for pretreatment. These effects were caused by
      dephosphorylation of SFKs, as confirmed by the specific SFK inhibitor SRC
      inhibitor 1, leading to dephosphorylation of the inhibitory immunoreceptors
      Siglec-9 and Siglec-3. The specific blocking of the latter also enhanced
      migration and underlined the importance of these SFK-dependent receptor systems
      for migration of moDCs. Dasatinib hampered the secretion of interleukin-12 by
      moDCs at clinically relevant concentrations. In contrast, endocytosis or boosting
      of cytomegalovirus-specific CD8(+) T-cell responses remained unaltered when
      applying dasatinib-pretreated moDCs, in line with minor effects on the expression
      of co-stimulatory molecules essential for DC-T cell interaction. The induction of
      enhanced migration of moDCs may potentially be useful in chemo-immunotherapeutic
      applications. Thus, the use of dasatinib or blocking Siglec antibodies as
      adjuvants in this setting to induce stronger immune responses is worthy of
      further study. 

PMID- 24882274
TI  - oxLDL/beta2GPI/anti-beta2GPI complex induced macrophage differentiation to foam
      cell involving TLR4/NF-kappa B signal transduction pathway.
AB  - Macrophage-derived foam cell formation is a hallmark of atherosclerosis. It has
      been reported that oxidized low density lipoprotein (oxLDL) inducing formation of
      foam cells and expression of inflammatory molecules are partly mediated by toll
      like receptor 4 (TLR4)/nuclear factor kappa B (NF-kappaB) pathway. However,
      whether oxLDL/beta2-glycoprotein I/anti-beta2-glycoprotein I (oxLDL/beta2GPI/anti
      beta2GPI) complex enhanced formation of foam cells involving TLR4/NF-kappaB
      pathway or not has never been explored. In the current study, we focused on
      investigating the transformation of peritoneal macrophages from BALB/c mice into
      foam cells induced by the three complexes, and the involvement of TLR4 as well as
      its downstream signal molecule NF-kappaB. The results showed that treatment of
      macrophages with oxLDL/beta2GPI/anti-beta2GPI complex could markedly increase
      intracellular lipid loading and expression of TLR4, phosphorylated NF-kappaB p65
      (p-NF-kappaB p65), monocyte chemoattractant protein-1 (MCP-1), as well as tissue
      factor (TF). The oxLDL and oxLDL/beta2GPI/anti-beta2GPI complex induced formation
      of foam cells and expression of p-NF-kappaB p65 were significantly reduced, while
      macrophages were pre-treated with TLR4 inhibitor TAK-242. Meanwhile, both TAK-242
      and NF-kappaB inhibitor PDTC could remarkably inhibit oxLDL, oxLDL/beta2GPI/anti
      beta2GPI complex, as well as LPS increased MCP-1 and TF levels. Nevertheless,
      beta2GPI/anti-beta2GPI complex-induced MCP-1 and TF mRNA expression were
      inhibited by TAK-242 rather than PDTC, although TF activity was significantly
      reduced by both of the inhibitors. In conclusion, our results indicate that
      oxLDL/beta2GPI/anti-beta2GPI complex could enhance the conversion of macrophages
      into foam cells and the process may be at least partly mediated by TLR4/NF-kappaB
      pathway, which may contribute to the accelerated development of atherosclerosis
      in APS. 

PMID- 24882275
TI  - Which dose of steroids and which cytotoxics for severe lupus?
AB  - There have been a number of major advances in the treatment of systemic lupus
      erythematosus and we are now in the era of biologic therapies for this
      multisystem autoimmune disorder. There has been a greater awareness of the
      toxicities of the traditional therapies including the recognition that the doses
      of corticosteroids used in the past have been excessive, resulting in
      unacceptable toxicities. Other advances have included the development of lower
      cumulative doses of cyclophosphamide and the widespread acceptance of
      mycophenolate mofetil for the treatment of lupus nephritis. This review addresses
      the current management of severe lupus with corticosteroids and cytotoxic agents.

PMID- 24882276
TI  - Parenteral oestrogen: effective and safer than both oral oestrogen and
      contemporary androgen deprivation therapy for prostate cancer?

PMID- 24882277
TI  - Do prostate cancer nomograms give accurate information when applied to European
      patients?
AB  - OBJECTIVE: The aim of this study was to validate and compare the performance of
      preoperative risk assessment tools in a population of men treated with radical
      prostatectomy at a single European institution. MATERIAL AND METHODS: Patients
      were identified from databases of radical prostatectomy between 1996 and 2011
      from a single UK centre. Information was obtained on demographics, prostate
      specific antigen, staging, biopsy and specimen histopathology, and follow-up.
      Data were inputted into the Memorial Sloan-Kettering Cancer Center (MSKCC),
      Partin 1997 and Makarov/Partin 2007 nomograms, and the University of California
      San Francisco-Cancer of the Prostate Risk Assessment tool (UCSF-CAPRA). The risks
      of extracapsular extension (ECE), seminal vesicle invasion (SVI) and lymph-node
      involvement (LNI) were calculated and compared with known outcomes. Nomogram
      performance was measured using Hosmer-Lemeshow (HL) goodness-of-fit tests,
      calculating concordance indices (c-indices) and calibration curves. RESULTS: Data
      were obtained for 541 patients. Prediction of ECE was relatively poor using all
      nomograms, with the Makarov/Partin 2007 the most accurate at prediction over the
      range of risk stratification (HL 9.9, c-index 0.62). Predictions of SVI and LNI
      were better than for ECE, with the MSKCC nomogram performing best for SVI (HL
      10.9, c-index 0.73) and all nomograms performing well for LNI prediction (c
      indices 0.8 to 0.815). CAPRA predicted best for SVI (OR 1.49, 95% confidence
      interval 1.27-1.74). CONCLUSIONS: To the authors' knowledge, this is the first
      head-to-head comparison of the accuracy of these commonly used risk calculators
      in a North European population. Caution should be used when counselling patients
      using nomograms. Although nomograms may be used as a guide, patients should be
      warned that they often have not been validated on different European populations
      and may give misleading information regarding a patient's specific risks.

PMID- 24882278
TI  - Fibril aggregates formed by a glatiramer-mimicking random copolymer of amino
      acids.
AB  - Amyloid formation is now considered a universal and intrinsic property of all
      proteins, irrespective of their sequences. Therefore, it is interesting to see
      whether random copolymers of amino acids can also form amyloid aggregates. Here
      we use a copolymer of 4 amino acids, mimicking the clinically used drug
      Glatiramer, and demonstrate that it does form amyloid-like fibrils in the aqueous
      solution despite its random sequence structure. The fibrillar aggregates show an
      alanine-rich beta-sheet secondary structure, proving the high tolerance of
      amyloid aggregates to the sequence irregularity in poly(amino acid)s, and
      suggesting the potential application of random copolymers as amyloid materials. 

PMID- 24882279
TI  - Invited commentary.

PMID- 24882280
TI  - Invited commentary.

PMID- 24882281
TI  - Invited commentary.

PMID- 24882282
TI  - Invited commentary.

PMID- 24882283
TI  - Invited commentary.

PMID- 24882284
TI  - Invited commentary.

PMID- 24882285
TI  - Invited commentary.

PMID- 24882286
TI  - Invited commentary.

PMID- 24882287
TI  - Invited commentary.

PMID- 24882288
TI  - Invited commentary.

PMID- 24882289
TI  - Invited commentary.

PMID- 24882290
TI  - Invited commentary.

PMID- 24882291
TI  - Invited commentary.

PMID- 24882292
TI  - Three-dimensional printing for perioperative planning of complex aortic arch
      surgery.
AB  - PURPOSE: In this study, we show the use of three-dimensional printing models for
      preoperative planning of surgery for patients with complex aortic arch anomalies.
      DESCRIPTION: A 70-year-old man with an extensively arteriosclerotic aneurysm
      reaching from the ascending aorta to the descending aorta was referred to our
      center for complete aortic arch replacement. We visualized and reconstructed
      computed tomography data of the patient and fabricated a flexible three
      dimensional model of the aortic arch including the aneurysm. EVALUATION: This
      model was very helpful for the preoperative decision making and planning of the
      frozen elephant trunk procedure owing to the exact and lifelike illustration of
      the native aortic arch. CONCLUSIONS: Three-dimensional models are helpful in
      preoperative planning and postoperative evaluation of frozen elephant trunk
      procedures in patients with complex aortic anatomy.

PMID- 24882293
TI  - Invited commentary.

PMID- 24882294
TI  - Rewarming a patient with accidental hypothermia and cardiac arrest using thoracic
      lavage.
AB  - The optimal treatment for severe accidental hypothermia is cardiopulmonary bypass
      because this offers the most rapid rate of rewarming. However, cardiopulmonary
      bypass therapy is not available in every hospital. In these circumstances,
      rewarming has to be achieved with other methods. We present a patient who was
      successfully rewarmed with thoracic lavage after he had been found with a core
      temperature of 21 degrees C and asystole. 

PMID- 24882295
TI  - Chest tube entrapment: a simple solution for technical error.
AB  - Unrecognized chest tube entrapment by surgical closure is a technical error. We
      present a rare case of chest tube entrapment that was successfully treated with a
      simple and safe solution in an elderly man after coronary artery bypass grafting
      (CABG). We visualized the suture using a small endoscope through the chest tube
      and incised it with the help of thoracoscopic scissors. The tube was then removed
      without the need for surgical exploration. 

PMID- 24882296
TI  - Salvage operation for late recurrence after stereotactic body radiotherapy for
      lung cancer: two patients with no viable cancer cells.
AB  - We report two patients who underwent salvage lung resection for suspected local
      recurrence on computed tomography image findings after stereotactic body
      radiotherapy; however, the pathologic findings indicated no viable tumor cells.
      Distinguishing between posttreatment changes and tumor recurrence after
      stereotactic body radiotherapy on the image findings is difficult; therefore, the
      determination of surgical indications requires comprehensive evaluations. 

PMID- 24882297
TI  - Simple technique for reconstruction of superior vena cava and brachiocephalic
      vein after removal for thoracic malignancies.
AB  - A ringed polytetrafluoroethylene graft was applied to reduce clamping time for a
      patent major vein. In case 1, after suturing the ringed graft to the right
      appendage, the other end was inserted in the distal direction of the left
      brachiocephalic vein and secured by ligation. In case 2, to repair an extensive
      superior vena cava defect, the graft was wrapped with the remnant venous wall and
      fixed with a continuous suture. Only 5 minutes were required to reconstruct the
      left brachiocephalic vein and 20 minutes for the superior vena cava. Long-term
      graft patency was obtained without thrombosis. 

PMID- 24882298
TI  - Metastatic meningioma extending into the left atrium through the pulmonary vein.
AB  - Left atrial extension of pulmonary tumors through the pulmonary vein is most
      often associated with primary malignancies and is rarely associated with
      metastatic disease. We present the first, to our knowledge, reported case of a
      patient with a history of intracranial meningioma resections presenting with
      metastatic meningioma to the right lower lobe with extension into the left atrium
      through the pulmonary vein. 

PMID- 24882299
TI  - Intravenous immunoglobulin-induced hemolytic anemia after thoracoscopic
      thymectomy for myasthenia gravis.
AB  - A 24-year-old woman underwent video-assisted thoracoscopic thymectomy for
      Osserman IIB myasthenia gravis (MG). In preparation for thymectomy, high-dose
      intravenous immunoglobulin (IVIG) was administered 1 week before the surgical
      procedure. After uneventful thoracoscopic thymectomy, the postoperative
      hemoglobin value decreased from 12.1 mg/dL to 8.2 mg/dL. A diagnosis of IVIG
      associated hemolytic anemia was made based on a peripheral smear with numerous
      spherocytes, a positive direct antiglobulin test result, and increased
      reticulocyte count. Hemoglobin levels after IVIG administration should be
      monitored closely before and after elective surgical procedures to identify
      severe anemia. Transfusion of type-matched blood should be avoided and risk
      factors understood. 

PMID- 24882300
TI  - Dramatic improvement after bilateral diaphragmatic plication in Charcot-Marie
      Tooth disease.
AB  - A 52-year-old woman with Charcot-Marie-Tooth disease presented with severe
      dyspnea due to bilateral diaphragmatic paralysis severely compromising
      respiratory function. There was little in the available literature to guide us
      regarding management of this unusual condition, and after deliberation, we
      decided to treat her with a staged plication of bilateral hemidiaphragms.
      Postoperatively, she demonstrated very good symptomatic relief supported by
      objective evidence, including improvement in lung function tests. We describe our
      management of this difficult condition, including the surgical and anesthetic
      considerations, and would recommend bilateral diaphragmatic plication as an
      effective option in patients with this unfortunate disease. 

PMID- 24882301
TI  - Thoracoscopy-assisted minimally invasive surgical stabilization of the
      anterolateral flail chest using Nuss bars.
AB  - Flail chest is caused by complex fractures of multiple ribs as a result of severe
      chest injuries, which results in paradoxical chest movements that severely
      compromise respiratory function. We report our experience of thoracoscopically
      assisted, minimally invasive surgical stabilization of massive anterolateral
      flail chest using a Nuss bar in three patients. This technique offers effective
      stabilization while having the advantages of short surgical time, minimal blood
      loss, less trauma, quicker recovery, and small and inconspicuous incisions. 

PMID- 24882302
TI  - High-speed 3-dimensional imaging in robot-assisted thoracic surgical procedures.
AB  - We used a high-speed 3-dimensional (3D) image analysis system (SYNAPSE VINCENT,
      Fujifilm Corp, Tokyo, Japan) to determine the best positioning of robotic arms
      and instruments preoperatively. The da Vinci S (Intuitive Surgical Inc,
      Sunnyvale, CA) was easily set up accurately and rapidly for this operation.
      Preoperative simulation and intraoperative navigation using the SYNAPSE VINCENT
      for robot-assisted thoracic operations enabled efficient planning of the
      operation settings. The SYNAPSE VINCENT can detect the tumor location and depict
      surrounding tissues quickly, accurately, and safely. This system is also
      excellent for navigational and educational use. 

PMID- 24882303
TI  - Treatment of giant pharyngoesophageal diverticulum by video-assisted
      thoracoscopy.
AB  - A 67-year-old woman presented with a giant pharyngoesophageal diverticulum
      (Zenker's diverticulum) that extended deep into the chest. Surgery, using either
      an open or endoscopic approach, was difficult. We stapled the common wall between
      the diverticulum and the esophagus using video-assisted thoracoscopic surgery.
      The patient exhibited good anatomic and functional results at 6 months' follow
      up. 

PMID- 24882304
TI  - Ross procedure for patient with Marfan syndrome.
AB  - The most prominent long-term complication after the Ross procedure is the risk of
      autograft dilatation, and therefore its application in patients at increased
      perceived risk of autograft dilatation (those with bicuspid aortic valve disease,
      aortic insufficiency [AI] with dilated aorta, collagen vascular diseases such as
      Marfan syndrome) has been discouraged. We reported a modified Ross procedure in
      2005 in which the autograft was completely encased in a polyester graft before
      implantation to prevent further dilatation of the autograft. This case report
      describes follow-up of a patient with Marfan syndrome who underwent this modified
      Ross procedure in July 2005. 

PMID- 24882305
TI  - Acute dilatation of the ascending aorta and aortic valve regurgitation in Loeys
      Dietz syndrome.
AB  - Loeys-Dietz syndrome (LDS) is a recently recognized connective tissue disorder
      caused by mutations of the transforming growth factor (TGF)-beta receptors. It is
      an autosomal dominant syndrome characterized by the triad of arterial tortuosity
      and aneurysms, hypertelorism, and bifid uvula or cleft palate. We treated an 18
      year-old woman with a 100-mm-diameter aortic root aneurysm and severe aortic
      valve regurgitation. She underwent urgent aortic root replacement and
      bioprosthetic valve implantation. LDS was diagnosed by postoperative genetic
      screening results. Histopathologic examination of the aortic wall showed diffuse
      degeneration and elastin fragmentation in the media. 

PMID- 24882306
TI  - Anomalous left coronary artery in hypertrophic cardiomyopathy.
AB  - Hypertrophic cardiomyopathy and anomalous origin of the coronary artery from the
      opposite sinus are common causes of sudden cardiac death. These entities have
      rarely been reported together. Here we present the case of a 48-year-old woman
      with hypertrophic cardiomyopathy and significant left ventricular outflow tract
      obstruction. She was referred for septal reduction therapy for symptomatic left
      ventricular outflow tract obstruction refractory to medical therapy. Cardiac
      catheterization and coronary artery computed tomography angiogram revealed a
      single coronary artery arising from the right sinus of Valsalva, coursing between
      the aorta and the right ventricular outflow tract. The patient underwent septal
      myectomy and placement of an implantable cardioverter defibrillator. 

PMID- 24882307
TI  - Coil embolization of persistent false lumen after type A dissection repair.
AB  - A 44-year-old man with a type A dissection repair 5 years earlier presented with
      progressive enlargement of the residual arch and thoracic aorta. Flow into the
      false lumen from the distal aortic suture line was evident on contrast-enhanced
      computed tomography. Through a redo hemisternotomy, the false lumen was accessed
      directly. An Amplatzer plug was deployed within the narrowed neck of the false
      lumen proximal to the enlarged false lumen within descending aorta. Interlocking
      coils were deployed proximal to the Amplatzer plug, resulting in thrombosis of
      the false lumen. 

PMID- 24882308
TI  - Management of a left atrial intramural hematoma after percutaneous intervention.
AB  - Left atrial intramural hematoma is a rare complication of percutaneous
      intervention. We report the case of a 69-year-old man with recurrent angina after
      CABG 19 years ago who was admitted for percutaneous intervention. After an
      attempt to recanalize the native circumflex artery and the vein graft, he had a
      cardiac arrest and was resuscitated successfully. Transesophageal
      echocardiography showed a large expanding hematoma within the left atrial wall
      causing obstruction of the mitral valve and compressing the right atrium from
      across the septum. An emergency thoracotomy was performed and with
      transesophageal echocardiography guidance and left atrial intramural hematoma was
      drained successfully. 

PMID- 24882309
TI  - Pulmonary infarction from a fractured and embolized central venous catheter.

PMID- 24882311
TI  - Extraadrenal biatrial cardiac paraganglioma: diagnosis, histological criteria and
      surgical management.

PMID- 24882310
TI  - Glandular papillomas originating from posterior segment of right upper lung
      simulating a mass from trachea.

PMID- 24882312
TI  - Patent coronary artery 23 years after direct closure of coronary artery aneurysm.

PMID- 24882313
TI  - Cervicothoracic airway injury repair using double-wide intercostal muscle flap.
AB  - We present a useful technique for the surgical management of long-segment
      cervicothoracic tracheobronchial injury using a double-wide intercostal muscle
      flap. This flap is a modification of a previously endorsed technique extending
      the ability to reinforce repairs of tracheobronchial injuries not adequately
      covered by a single intercostal muscle flap. 

PMID- 24882314
TI  - Pulmonary patch repair of tracheobronchial necrosis with perforation secondary to
      caustic ingestion.
AB  - Corrosive aerodigestive injury complicated by tracheobronchial necrosis is a rare
      complication after caustic ingestion that carries a high risk of mortality and
      morbidity. If left untreated, tracheobronchial necrosis results in perforation,
      mediastinitis, and death. Pulmonary patch repair is a safe, effective, and easily
      performed surgical technique for the treatment of tracheobronchial necrosis with
      perforation. Frequent endoscopic surveillance leads to early diagnosis and prompt
      operative management to prevent significant morbidity. We describe a pulmonary
      patch repair of a patient who had stage 3b necrosis of the esophagus and the
      stomach with tracheobronchial necrosis and perforation after caustic ingestion. 

PMID- 24882315
TI  - Use of combined suspension laryngoscopy and jet ventilation for Y-shaped airway
      stents delivery.
AB  - Airway stenting is a common endoscopic procedure that is used to treat a variety
      of central airway lesions. Obstructions or fistulas involving the carina or
      nearby tracheobronchial structures require the use of specially designed stents,
      commonly referred to as Y-stents. Conventional methods of endobronchial Y-stent
      delivery are all characterized by a blind and apneic period during the procedure
      that carries the risk of stent misplacement or ventilation/oxygenation problems
      or both. Using combined suspension laryngoscopy, flexible bronchoscopy, and jet
      ventilation, we describe a technique that makes challenging bronchoscopic
      interventions--such as self-expandable Y-shaped airway stent delivery--easy,
      precise, and safe.

PMID- 24882316
TI  - Aortic valve annuloplasty: new single suture technique.
AB  - Reconstruction strategies for aortic valve insufficiency in the presence of
      aortic annulus dilatation are usually surgically challenging. We demonstrate a
      simple, modified Taylor technique of downsizing and stabilization of the aortic
      annulus using a single internal base suture. Since April 2011, 22 consecutive
      patients have undergone safe aortic valve annuloplasty. No reoperations for
      aortic valve insufficiency and no deaths occurred. 

PMID- 24882317
TI  - Off-pump HeartWare ventricular assist device implantation with outflow graft
      anastomosis to the left subclavian artery.
AB  - A novel, off-pump implantation technique for the HeartWare ventricular assist
      device with outflow graft anastomosis to the left subclavican artery is
      described. Cannulation of the left ventricular apex is performed through an
      incision in the left fourth or fifth intercostal space. The outflow graft is
      anastomosed to the left subclavian artery after tunneling through the left
      thoracic cavity and the first intercostal space. This technique is especially
      appealing in redo cases as well as in patients with significant calcifications of
      the ascending aorta or in destination-therapy patients. 

PMID- 24882318
TI  - Smart placement of a mediastinal drain in a neonate who requires a postoperative
      open sternum.
AB  - Crowding of the mediastinum after complex cardiac repair procedures in neonates
      and young children is a frequent problem. To create space, the sternal wound is
      kept open, commonly with a plastic stent, for later closure. Despite this
      maneuver, space is still an issue, and appropriate placement of the mediastinal
      drain can become a challenge. In this article we describe a simple and effective
      way to eliminate the problem. Holes are made in the sternal stent, and the drain
      is pulled through these holes. The drain is elevated away from the heart surface
      and does not contribute to the crowding. 

PMID- 24882319
TI  - Reply: To PMID 23545194.

PMID- 24882320
TI  - Concurrent radiochemotherapy in stage IIIA non-small-cell lung cancer: not just
      effectiveness but very low toxicity.

PMID- 24882321
TI  - Prognostic significance of lymph node counts in operable esophageal cancer.

PMID- 24882322
TI  - Reply: To PMID 23866797.

PMID- 24882323
TI  - Is preoperative hematocrit really a predictor of adverse outcomes after coronary
      artery bypass grafting?

PMID- 24882324
TI  - Reply: To PMID 24055236.

PMID- 24882325
TI  - Aspartate aminotransferase and survival after cardiac surgical procedures.

PMID- 24882326
TI  - Is microplegia superior to regular blood cardioplegia during coronary artery
      bypass grafting?

PMID- 24882327
TI  - Reply: To PMID 22841017.

PMID- 24882328
TI  - Retrograde cardioplegia for myocardial protection during arterial switch
      operation.

PMID- 24882329
TI  - Reply: To PMID 23608252.

PMID- 24882330
TI  - Reply: To PMID 23462260.

PMID- 24882331
TI  - Strangulation of chronic transdiaphragmatic intercostal hernia.
AB  - Transdiaphragmatic intercostal hernia (TIH) caused by violent coughing is a rare
      clinical diagnosis. Most patients diagnosed with TIH have a chronic condition
      consisting of a hernia that can be reduced completely by surgical intervention.
      Our patient presented with acute abdomen resulting from mechanical bowel
      obstruction secondary to an incarcerated hernia. Acute TIH presents a diagnostic
      challenge because of its rarity and lack of specific signs or symptoms in the
      differential diagnosis of acute abdomen. We recommend performing diagnostic
      computed tomography (CT) early if there is suspicion of TIH. Surgical
      intervention is always needed. Surgical intervention was complicated in this
      case, necessitating both transthoracic and abdominal exposure to resect the
      ischemic bowel segment. Nonetheless, the patient recovered uneventfully. 

PMID- 24882333
TI  - Transjugular approach in valve-in-valve transcatheter mitral valve replacement:
      direct route to the valve.
AB  - With the recent emergence of transcatheter valve replacement, high-risk cases of
      structural valve deterioration after mitral bioprosthesis can be treated with
      valve-in-valve transcatheter mitral valve replacement (TMVR). The transapical
      approach has become the principal access for TMVR, but we report an alternative
      direct access for TMVR--transjugular transseptal route--in an 81-year-old woman
      with a degenerated mitral bioprosthesis.

PMID- 24882332
TI  - Transcatheter aortic valve implantation in a lung transplant recipient.
AB  - Transcatheter aortic valve implantation is a feasible therapeutic option for
      selected patients with severe aortic stenosis and high or prohibitive risk for
      standard surgery. Lung transplant recipients are often considered high-risk
      patients for heart surgery because of their specific transplant-associated
      characteristics and comorbidities. We report a case of successful transfemoral
      transcatheter aortic valve replacement in a lung transplant recipient with a
      symptomatic severe aortic stenosis, severe left ventricular dysfunction, and end
      stage renal failure 9 years after bilateral lung transplantation. 

PMID- 24882334
TI  - Group B Streptococcus endocarditis with left ventricle-right atrium (Gerbode's)
      defect.
AB  - We report an unusual case of a 61-year-old woman with group B Streptococcus
      positive infective endocarditis and a left ventricular-right atrium or Gerbode's
      defect. We discuss the issues surrounding such an infection and the implications
      of such a rare cardiac defect in our case report. 

PMID- 24882335
TI  - Neonatal repair of truncus arteriosus with "scimitar-like" mixed total pulmonary
      venous return.
AB  - The association between truncus arteriosus and total anomalous pulmonary venous
      return is exceedingly rare. Here described is a neonate presenting with a common
      arterial trunk and a previously unreported "scimitar-like" mixed total pulmonary
      venous return who underwent a successful one-stage repair. The unprecedented
      anatomic pattern of the systemic and pulmonary venous connection and the original
      surgical strategy are discussed. 

PMID- 24882336
TI  - Novel technique for implantation of a cardioverter defibrillator in children.
AB  - An 8-year-old boy with hypertrophic nonobstructive cardiomyopathy with
      ventricular fibrillation underwent implantation of an implantable cardioverter
      defibrillator. The lead was inserted through a pursestring suture in the right
      atrial appendage, and the tip of coil was placed in the right ventricular apex
      under fluoroscopic guidance. Another defibrillation coil was placed in the back
      of the left atrium and left ventricle by the transverse sinus. The device wrapped
      in a monofilament mesh sheet was placed in the intraperitoneal space. This case
      utilized a new technique for an implantable cardioverter defibrillator
      implantation in a small child. 

PMID- 24882338
TI  - Aberrant vasculature during minimally invasive transhiatal esophagogastrectomy.

PMID- 24882337
TI  - Hybrid procedure as treatment for large obstructive left ventricular rhabdomyoma.
AB  - We present one of the first reported cases of a neonate with a prenatal diagnosis
      of large left ventricular rhabdomyoma obstructing the outflow tract that
      underwent a hybrid procedure with stenting of the patent duct arteriosus and
      bilateral pulmonary artery banding. 

PMID- 24882340
TI  - The peacock tail technique: a modified reconstruction technique for tricuspid
      valve repair in Ebstein's malformation.
AB  - The "peacock tail" technique is a modification of the cone reconstruction
      technique for Ebstein's malformation and failing right ventricle and is performed
      simultaneously with a bidirectional cavopulmonary shunt. The technique consists
      of total detachment of the posterior and anterior tricuspid valve leaflets, which
      are rotated simultaneously clockwise and counterclockwise and sutured at the
      midseptal leaflet level, forming a new tricuspid valve (TV). The constructed cone
      shaped valve is then attached in its entire circumference to the true tricuspid
      annulus. 

PMID- 24882339
TI  - Right atrial cardiac varix mimicking myxoma: differentiation using three
      dimensional echocardiography.

PMID- 24882341
TI  - Epidemiology of breast cancer.
AB  - This article outlines the current incidence, prevalence, and mortality of breast
      cancer and reviews the epidemiology of the disease. Major risk factors for the
      development of breast cancer are covered, including reproductive, genetic, and
      environmental variables. Understanding the epidemiology of breast cancer will
      help clinicians identify high-risk patients for appropriate screening and
      informed disease management decisions. 

PMID- 24882342
TI  - Prophylactic bilateral mastectomy and contralateral prophylactic mastectomy.
AB  - With increasing public awareness of the risk for breast cancer and modern
      techniques of reconstruction, the option of surgical prophylaxis for risk
      reduction is becoming increasingly popular. Bilateral prophylactic mastectomy for
      women at increased risk of developing breast cancer and contralateral
      prophylactic mastectomy for those with unilateral breast cancer seeking symmetry,
      risk reduction, and ease of follow-up are acceptable options for many women.
      However, prophylactic surgery is not an inconsequential decision, and careful
      consideration should be given to the risks and benefits of such procedures. 

PMID- 24882343
TI  - Applications for breast magnetic resonance imaging.
AB  - This article reviews the relevant data on breast magnetic resonance imaging (MRI)
      use in screening, the short-term surgical outcomes and long-term cancer outcomes
      associated with the use of MRI in breast cancer staging, the use of MRI in occult
      primary breast cancer, as well as MRI to assess eligibility for accelerated
      partial breast irradiation and to evaluate tumor response after neoadjuvant
      chemotherapy. MRI for screening is supported in specific high-risk populations,
      namely, women with BRCA1 or BRCA2 mutations, a family history suggesting a
      hereditary breast cancer syndrome, or a history of chest wall radiation. 

PMID- 24882344
TI  - Molecular profiling of breast cancer.
AB  - Breast cancer is now considered a heterogeneous and phenotypically diverse
      disease. Molecular profiling is used in clinical practice in 2 broad categories:
      (1) characterization of breast cancers beyond the standard histopathologic
      features such as tumor grade, histologic subtype, and biomarker profile for
      prognostic information; and (2) prediction of response to therapy and clinical
      outcome. This article addresses the importance and application of molecular
      subtype analysis, and provides an in-depth analysis of the clinical application
      of the molecular prognostic indices for ductal carcinoma in situ, node-negative
      invasive breast cancer, and node-positive invasive breast cancer. 

PMID- 24882345
TI  - Management of the clinically node-negative axilla in primary and locally
      recurrent breast cancer.
AB  - For patients with primary breast cancer, nodal status remains a key determinant
      for overall prognosis. Sentinel lymph node biopsy (SLNB) has become standard care
      for staging patients who have clinically node-negative disease. However, a new
      dilemma has arisen: how to manage the clinically negative axilla in patients with
      ipsilateral breast tumor recurrences (IBTRs). Are outcomes in these patients
      improved with repeat SLNB? Although observational studies suggest SLNB is
      feasible in patients with IBTR and a clinically node-negative axilla, the overall
      impact on morality and local recurrence is not yet known as no randomized trials
      have addressed this issue. 

PMID- 24882346
TI  - Management of axillary disease.
AB  - The presence of nodal metastases is the most important prognostic indicator in
      breast cancer, making accurate assessment of the axillary nodal basin critical to
      delivering optimal therapy in breast cancer. Clinically node-negative women can
      be reliably staged in a minimally invasive manner using sentinel lymph node
      dissection (SLND). In node-negative patients receiving neoadjuvant chemotherapy,
      SLND can be performed after chemotherapy, allowing for a single surgical
      procedure and a decreased probability of requiring axillary lymph node dissection
      (ALND). Clinically node-positive patients are currently recommended to undergo
      ALND, although these recommendations may change with emerging trial data. 

PMID- 24882347
TI  - Lobular neoplasia.
AB  - Lobular neoplasia (LN) is characterized by a dysfunctional E-cadherin-catenin
      axis, and loss of E-cadherin plays a causative role in the typical morphology of
      LN cells. LN is both a nonobligate precursor and a risk indicator of invasive
      breast cancer, and in particular, of invasive lobular carcinoma. Despite the
      evidence supporting the precursor role of LN, its impact on clinical management
      has been a matter of controversy, and conservative management remains the
      mainstay of treatment. In this article, an update is provided on the pathology
      and genetics of LN, and the management of these lesions in surgical practice is
      discussed. 

PMID- 24882349
TI  - Advances in breast reconstruction of mastectomy and lumpectomy defects.
AB  - Breast reconstruction continues to evolve along with advances in the detection
      and management of breast cancer. With more patients diagnosed with breast cancer
      earlier in life and increased identification of genetic mutations predisposing
      patients to breast cancer, patients' desires and expectations regarding
      reconstruction have become more sophisticated. Restoration of the breast to a
      form as close as possible to its presurgical state continues to be a primary
      goal. The past decade has seen many advances in implant and autologous tissue
      based reconstruction. The future of reconstruction for breast cancer patients is
      promising with continued research in ways to improve the care provided. 

PMID- 24882348
TI  - Neoadjuvant therapy in the treatment of breast cancer.
AB  - Neoadjuvant systemic therapy in breast cancer treatment was initially utilized
      for inoperable disease. However, several randomized prospective studies have
      demonstrated comparable survival with adjuvant chemotherapy in early-stage,
      operable breast cancer while also decreasing tumor size facilitating breast
      conservation without significant increases in local recurrence. Response to
      therapy can predict outcome, with improved survival associated with pathologic
      complete response (pCR). Triple negative and HER2-positive subtypes show
      increased pCR rates. A multidisciplinary approach is necessary with neoadjuvant
      treatment. This can improve rates of breast conservation, provide insights into
      tumor biology and predict patient outcomes. 

PMID- 24882350
TI  - Nipple-sparing mastectomy: an oncologic and cosmetic perspective.
AB  - The guiding principles of nipple-sparing mastectomy (complete removal of the
      breast from its skin and reconstructing without changing the appearance of the
      breast) are based on patient safety followed by oncologic safety. Recent advances
      have also taken into account cosmetic outcome. The ultimate in cosmetic outcome
      after mastectomy with reconstruction includes preservation of the nipple-areola
      complex, called a nipple-sparing mastectomy. The evidence-based transition and
      transformation to nipple-sparing mastectomy from both an oncologic standpoint and
      a cosmetic perspective are outlined in this article. 

PMID- 24882352
TI  - Breast cancer disparities: high-risk breast cancer and African ancestry.
AB  - African American women have a lower lifetime incidence of breast cancer than
      white/Caucasian Americans yet have a higher risk of breast cancer mortality.
      African American women are also more likely to be diagnosed with breast cancer at
      young ages, and they have higher risk for the biologically more aggressive triple
      negative breast cancers. These features are also more common among women from
      western, sub-Saharan Africa who share ancestry with African Americans, and this
      prompts questions regarding an association between African ancestry and inherited
      susceptibility for certain patterns of mammary carcinogenesis. 

PMID- 24882351
TI  - Basal-like and triple-negative breast cancers: searching for positives among many
      negatives.
AB  - Triple-negative breast cancers (TNBC) are defined by their failure to express the
      estrogen receptor, progesterone receptor, and HER2/neu protein markers. This
      basic feature is clinically relevant because it indicates that these cancers
      cannot be managed with endocrine or anti-HER2 systemic therapies. Furthermore,
      most TNBC cases are also characterized as being of the genetically defined basal
      subtype, which is an inherently and biologically more aggressive pattern of
      disease. The two terms, however, are not synonymous, and some TNBC cases are
      prognostically more favorable. TNBC differs from non-TNBC in risk-factor profile,
      pattern, and rate of metastatic spread. 

PMID- 24882353
TI  - Nonsurgical ablation of breast cancer: future options for small breast tumors.
AB  - The surgical management of breast cancer has evolved significantly, facilitated
      by advancements in technology and imaging and improvements in adjuvant therapy.
      The changes in surgical management have been characterized by equal or improved
      outcomes with significantly less morbidity. The next step in this evolution is
      the minimally invasive or noninvasive ablation of breast cancers as an
      alternative to lumpectomy. In this article, the various modalities for
      nonsurgical breast cancer ablation and the clinical experience are reviewed, and
      some of the next steps necessary for their clinical implementation are outlined. 

PMID- 24882354
TI  - Surgical leadership and standardization of multidisciplinary breast cancer care:
      the evolution of the National Accreditation Program for Breast Centers.
AB  - Evidence has shown that multidisciplinary specialist team evaluation and
      management for cancer results in better patient outcomes. For breast cancer,
      breast centers are where this evaluation and management occurs. The National
      Accreditation Program for Breast Centers has helped standardize multidisciplinary
      breast cancer care by defining services and standards required of accredited
      breast centers. 

PMID- 24882355
TI  - Breast cancer.

PMID- 24882356
TI  - Breast cancer.

PMID- 24882357
TI  - A temporary compendium of thyroid hormone target genes in brain.
AB  - BACKGROUND: Thyroid hormone controls a number of developmental and physiological
      processes in the brain by directly acting on gene expression. Transcriptome
      analyses in rodent identified a number of thyroid hormone regulated genes in
      several brain areas at different stages. Genome wide analysis of chromatin
      occupancy in a neural cell line also identified a subset of genes which
      transcription is likely to be directly regulated by thyroid hormone receptors in
      neurons. However, the abundance of these data and apparent discrepancies between
      studies brought some confusion. RESULTS: We present here a meta-analysis of
      available data to identify recurrent themes in thyroid hormone action in brain
      cells. This provides a curated list of 734 regulated genes in rodent brain, and
      highlights a small number of likely direct target genes. Some of these genes are
      also regulated in amphibians during metamorphosis. This article is part of a
      Special Issue entitled: Nuclear receptors in animal development.

PMID- 24882358
TI  - Nuclear receptors and Drosophila neuronal remodeling.
AB  - During the development of both vertebrates and invertebrates, neurons undergo a
      crucial remodeling process that is necessary for their new function. Neuronal
      remodeling is composed of two stages: first, axons and dendrites are pruned
      without the loss of the cell body; later, this process is most commonly followed
      by a regrowth step. Holometabolous insects like the fruitfly Drosophila exhibit
      striking differences between their larval and adult stages. These neuronal
      remodeling processes occur during metamorphosis, the period of transformation
      from a larva to an adult. All axon and dendrite pruning events ultimately depend
      on the EcR nuclear receptor. Its ligand, the steroid molting hormone ecdysone,
      binds to heteromeric receptors comprising the nuclear receptor ECR and USP, and
      this complex regulates target genes involved in neuronal remodeling. Here we
      review the nuclear receptor-mediated genetic control of the main neuronal
      remodeling events described so far in Drosophila. These events consist of neurite
      degeneration in the mushroom bodies (MBs: the brain memory center) and in the
      dendritic arborizing sensory neurons, of neurite retraction or small scale
      elimination in the thoracic ventral neurosecretory cells, in the olfactory
      circuits and in the neuromuscular junction. MB axon regrowth after pruning and
      the role of MB neuron remodeling in memory formation are also reviewed. This
      article is part of a Special Issue entitled: Nuclear receptors in animal
      development. 

PMID- 24882359
TI  - Direct assessment of the mechanical modulus of graphene co-doped with low
      concentrations of boron-nitrogen by a non-contact approach.
AB  - Boron and nitrogen co-doping has been shown to be an effective way to induce a
      band gap in graphene for electrical applications but only a few theoretical
      studies have been done to understand the elastic and mechanical properties of the
      modified graphene. Until now, no experimental assessment of the mechanical
      modulus of boron-nitrogen-doped graphene (BNG) has been reported in the
      literature. Here, we demonstrate a novel non-contact approach to determine the in
      plane stiffness of BNG at low BN concentrations. The in-plane stiffness of BNG
      with 2 at% BN concentration was estimated to be about 309 N m(-1), which is lower
      than that of pristine graphene, in good agreement with some theoretical studies.
      Moreover, we correlated the conductivity of BNG with induced strain and found the
      BNG to be more sensitive than pristine graphene in response to externally applied
      strain. This result indicates that BNG is a more suitable material than graphene
      for strain sensor applications. 

PMID- 24882360
TI  - Interaction of Grb2 SH3 domain with UVRAG in an Alzheimer's disease-like
      scenario.
AB  - Growth factor receptor-bound protein 2 (Grb2) is an adaptor protein which
      participates in trafficking pathways alongside its role in signaling. Proteins
      important for actin remodeling and cellular compartmentalization contain SRC
      Homology 3 (SH3) binding motifs that interact with Grb2. While studying the Grb2
      amyloid precursor protein (APP) intracellular domain (AICD) interaction in
      Alzheimer's disease cell line models, it was seen that Grb2 colocalized to
      compartments that mature into autophagosomes. The entrapping of AICD in the Grb2
      vesicles and its clearance via autophagosomes was a survival contrivance on the
      part of the cell. Here, we report that Grb2, when in excess, interacts with
      ultraviolet radiation resistance-associated gene protein (UVRAG) under excess
      conditions of AICD-Grb2 or Grb2. The N-terminal SH3 domain of Grb2 specifically
      interacts with UVRAG, unlike the C-terminal SH3 domain. This interaction helps to
      understand the role of Grb2 in the autophagic maturation of vesicles. 

PMID- 24882361
TI  - Dendritic polyglycerol-poly(ethylene glycol)-based polymer networks for
      biosensing application.
AB  - This work describes the formation of a new dendritic polyglycerol-poly(ethylene
      glycol)-based 3D polymer network as a matrix for immobilization of the redox
      enzyme periplasmatic aldehyde oxidoreductase to create an electrochemical
      biosensor. The novel network is built directly on the gold surface, where it
      simultaneously stabilizes the enzyme for up to 4 days. The prepared biosensors
      can be used for amperometric detection of benzaldehyde in the range of 0.8-400
      MUM. 

PMID- 24882362
TI  - A chiral BINOL-bridged imidazole dimer possessing sub-millisecond fast
      photochromism.
AB  - We developed a chiral 1,1'-bi-2-naphthol-bridged imidazole dimer possessing 100
      MUs fast photochromism and high fatigue resistance. It offers great opportunities
      for the practical applications to fast photoresponsive chiral dopants, invisible
      security materials and optical trigger molecules to induce the dynamic structural
      changes in biological matters. 

PMID- 24882363
TI  - Processive cytoskeletal motors studied with single-molecule fluorescence
      techniques.
AB  - Processive cytoskeletal motors from the myosin, kinesin, and dynein families walk
      on actin filaments and microtubules to drive cellular transport and organization
      in eukaryotic cells. These remarkable molecular machines are able to take
      hundreds of successive steps at speeds of up to several microns per second,
      allowing them to effectively move vesicles and organelles throughout the
      cytoplasm. Here, we focus on single-molecule fluorescence techniques and discuss
      their wide-ranging applications to the field of cytoskeletal motor research. We
      cover both traditional fluorescence and sub-diffraction imaging of motors,
      providing examples of how fluorescence data can be used to measure biophysical
      parameters of motors such as coordination, stepping mechanism, gating, and
      processivity. We also outline some remaining challenges in the field and suggest
      future directions. 

PMID- 24882364
TI  - Synaptotagmin 11 interacts with components of the RNA-induced silencing complex
      RISC in clonal pancreatic beta-cells.
AB  - Synaptotagmins are two C2 domain-containing transmembrane proteins. The function
      of calcium-sensitive members in the regulation of post-Golgi traffic has been
      well established whereas little is known about the calcium-insensitive isoforms
      constituting half of the protein family. Novel binding partners of synaptotagmin
      11 were identified in beta-cells. A number of them had been assigned previously
      to ER/Golgi derived-vesicles or linked to RNA synthesis, translation and
      processing. Whereas the C2A domain interacted with the Q-SNARE Vti1a, the C2B
      domain of syt11 interacted with the SND1, Ago2 and FMRP, components of the RNA
      induced silencing complex (RISC). Binding to SND was direct via its N-terminal
      tandem repeats. Our data indicate that syt11 may provide a link between gene
      regulation by microRNAs and membrane traffic. 

PMID- 24882365
TI  - Results of an international transferability study of the BINACLE (binding and
      cleavage) assay for in vitro detection of tetanus toxicity.
AB  - Tetanus vaccines contain detoxified tetanus neurotoxin. In order to check for
      residual toxicity, the detoxified material (toxoid) has to be tested in guinea
      pigs. These tests are time-consuming and raise animal welfare issues. In line
      with the "3R" principles of replacing, reducing and refining animal tests, the
      "binding and cleavage" (BINACLE) assay for detection of active tetanus neurotoxin
      has been developed as a potential alternative to toxicity testing in animals.
      This in vitro test system can discriminate well between toxic and detoxified
      toxin molecules based on their receptor-binding and proteolytic characteristics.
      Here we describe an international study to assess the transferability of the
      BINACLE assay. We show that all participating laboratories were able to
      successfully perform the assay. Generally, assay variability was within an
      acceptable range. A toxin concentration-dependent increase of assay signals was
      observed in all tests. Furthermore, participants were able to detect low tetanus
      neurotoxin concentrations close to the estimated in vivo detection limit. In
      conclusion, the data from this study indicate that the methodology of the BINACLE
      assay seems to be robust, reproducible and easily transferable between
      laboratories. These findings substantiate our notion that the method can be
      suitable for the routine testing of tetanus toxoids. 

PMID- 24882366
TI  - Left middle frontal gyrus response to inhibitory errors in children prospectively
      predicts early problem substance use.
AB  - BACKGROUND: A core vulnerability trait for substance use disorder (SUD) is
      behavioral disinhibition. Error processing is a central aspect of inhibitory
      control that determines adaptive adjustment of performance; yet it is a largely
      overlooked aspect of disinhibition as it relates to risk for SUD. We investigated
      whether differences in brain activation during both successful and failed
      inhibition predicts early problem substance use. METHOD: Forty-five 9-12 year
      olds underwent a functional MRI scan during a go/no-go task. They were then
      followed over approximately 4 years, completing assessments of substance use.
      Externalizing behavior was measured at ages 3-8, 9-12 and 11-13. Participants
      with drug use or problem alcohol use by ages 13-16 (n=13; problem-user group)
      were individually matched by gender, age, and family history of alcoholism with
      non-substance-using children (n=13; non-user group). The remaining 19
      participants provided an independent sample from which to generate unbiased
      regions-of-interest for hypothesis testing in the problem-user and non-user
      groups. RESULTS: No differences were observed between groups in activation during
      correct inhibition compared with baseline. A significant difference arose in left
      middle frontal gyrus (LMFG) activation during failed inhibition compared with
      correct inhibition, with the problem-user group demonstrating blunted activation.
      The problem-user group also had more externalizing problems at ages 11-13.
      Logistic regression found that activation of LMFG significantly predicted group
      membership over and above externalizing problems. CONCLUSIONS: Blunted LMFG
      activation during performance errors may underlie problems adapting behavior
      appropriately, leading to undercontrolled behavior, early problem substance use
      and increased risk for SUD.

PMID- 24882367
TI  - Hookah use among college students: prevalence, drug use, and mental health.
AB  - BACKGROUND: There is consistent evidence that hookah use is as, if not more,
      harmful than cigarette use. Yet, hookah users underestimate the potential
      deleterious effects of hookah use. This study examined the rates of hookah use
      and associated demographic characteristics in a sample of undergraduates at a
      small Northeastern university. This study also examined the relationships between
      hookah use and other substance use, mental health problems, and perceived levels
      of stress. METHODS: Data were drawn from the Spring 2009 American Health
      Association-National College Health Assessment (ACHA-NCHA) at one small,
      Northeastern university (N=1799). The relationships between hookah use and other
      substance use, mental health problems, and perceived stress levels were examined
      using logistic regression analyses. RESULTS: Hookah use (in the past month) was
      reported among 14.1% (253/1799) of this sample of undergraduates. Hookah users
      were more likely to use other substances, including cigarettes, cannabis,
      alcohol, cocaine, and amphetamines. The strongest associations emerged between
      hookah use and alcohol and cigarette use. There were no significant associations
      found between hookah use and any mental health problems or perceived stress
      levels. CONCLUSIONS: Hookah users are significantly more likely to use other
      substances, including alcohol, cigarettes, cannabis, cocaine, and amphetamines
      compared with non-hookah users. In contrast to cigarette smoking, hookah use does
      not appear to be associated with mental health problems or perceived stress
      levels in this sample of undergraduates. Further investigation into the
      prevalence and correlates of hookah use is needed in representative population
      samples.

PMID- 24882368
TI  - Initial validation of the Mini-Mental Adjustment to Cancer (Mini-MAC) scale:
      study of Portuguese end-of-life cancer patients.
AB  - BACKGROUND: The Mini-Mental Adjustment to Cancer Scale (Mini-MAC) is a 29-item
      instrument designed to evaluate the responses developed by cancer patients during
      their mental adjustment to diagnosis and treatment. PURPOSE OF THE RESEARCH: This
      study aims to validate the Mini-Mental Adjustment to Cancer Scale (Mini-MAC)
      translated and adapted to the Portuguese language and culture, in end-of-life
      cancer patients receiving palliative care. METHODS AND DESIGN: The instrument was
      administered to 346 Portuguese end-of-life cancer patients, receiving care
      through outpatient visits or admitted into palliative care units, without
      cognitive symptoms and with symptoms under control. A cross-sectional validation
      study using orthogonal rotation through the varimax method followed by convergent
      and discriminant validity. KEY RESULTS: The analysis of the main components
      confirms the existence of five factors, demonstrating the validity of the
      construct, with good internal consistency in the subscales and Cronbach's alpha
      values between 0.78 and 0.93. Good test-retest reliability was also found, and r
      values for subscales ranged from 0.62 to 0.99. CONCLUSIONS: The instrument proved
      to be a reliable, valid and sensitive measure in the study of mental adjustment
      of Portuguese end-of-life patients with cancer receiving palliative care.
      RELEVANCE TO PRACTICE: Nurses can use the Mini-MAC Scale in research and clinical
      practice in order to evaluate the mental adjustment of Portuguese end-of-life
      cancer patients receiving palliative care.

PMID- 24882369
TI  - The concept and relevance of existential issues in nursing.
AB  - AIM: The aim of this study was to illuminate and clarify the concept of
      existential issues in relation to nursing research and nursing practice. METHODS:
      This article is a theoretical analysis of existential issues in relation to
      nursing. RESULTS: Existential issues are becoming more commonly discussed and
      investigated in nursing research. Thus, it is important to clarify the concept.
      CONCLUSIONS: A clarification of existential issues may contribute to health care
      quality by increasing awareness of what existential issues are and drawing
      attention to the importance of discussing and reflecting on these issues, since
      practitioners in a caring profession will most likely encounter them.

PMID- 24882370
TI  - Positive and cost-effectiveness effect of spa therapy on the resumption of
      occupational and non-occupational activities in women in breast cancer remission:
      a French multicentre randomised controlled trial.
AB  - PURPOSE OF THE RESEARCH: The main aim was to assess the effects of a spa
      treatment on the resumption of occupational and non-occupational activities and
      the abilities of women in breast cancer remission. A cost-effectiveness analysis
      (CEA) was also performed. METHODS AND SAMPLE: A multicentre randomised controlled
      trial was carried out between 2008 and 2010 in the University Hospital of
      Auvergne and two private hospitals in Clermont-Ferrand, France. Eligible patients
      were women in complete breast cancer remission without contraindication for
      physical activities or cognitive disorders and a body mass index between 18.5 and
      40 kg/m(2). The intervention group underwent spa treatment combined with
      consultation with dietician whereas the control underwent consultations with the
      dietician only. Of the 181 patients randomised, 92 and 89 were included in the
      intervention and the control groups, respectively. The CEA involved 90 patients,
      42 from the intervention group and 48 from the control group. KEY RESULTS: The
      main results showed a higher rate of resumption of occupational activities in the
      intervention group (p = 0.0025) and a positive effect of the intervention on the
      women's ability to perform occupational activities 12 months after the beginning
      of the study (p = 0.0014), and on their ability to perform family activities (p =
      0.033). The stay in a thermal centre was cost-effective at 12 months.
      CONCLUSIONS: Spa treatment is a cost-effective strategy to improve resumption of
      occupational and non-occupational activities and the abilities of women in breast
      cancer remission.

PMID- 24882371
TI  - Electromagnetic fields promote severe and unique vascular calcification in an
      animal model of ectopic calcification.
AB  - BACKGROUND: The effects of electromagnetic fields (EMFs) on cardiovascular
      calcification is unknown. We sought to evaluate the effects of EMF on vascular
      calcification in normal rats and in rats with chronic kidney disease (CKD) - a
      condition which promotes calcification. METHODS: We used four groups of rats:
      group 1 - exposed to EMF, group 2 - not exposed to EMF, group 3 - rats with CKD
      exposed to EMF, group 4 - rats with CKD not exposed to EMF. In order to induce
      CKD, groups 3 and 4 rats were fed with a uremia-inducing diet. Groups 1 and 3
      rats were continuously exposed to EMF using a system similar to an electrical
      transformer, which consists of a primary coil, a ferrite ring, and a secondary
      coil. The system transmitter emitted a series of exponentially decaying
      electromagnetic sine waves (continuous exposure with pulsed peaks) in randomly
      selected frequencies between 150 and 155 kHz, with random exposure intensities
      between 4 and 7 mG. Clinical investigations included multislice computed
      tomography of the aortic roots. Pathological examinations of the aortas included
      histological characterization, and antigen expression analyses. RESULTS: No
      calcification was found in either group of rats with normal kidney function.
      Aortic root calcification was significantly higher in rats exposed to EMF (group
      3) compared with group 4 rats - with a mean Agatston score of 138 +/- 25 vs. 80
      +/- 20 respectively (p<0.05). Pathological examination showed massive aortic
      calcification in group 3 rats. The calcification pattern was unique as it formed
      circular rings along the length of the aortic media. Although increased
      calcification was noticed in group 3 rats, antigen expression of osteoblast
      markers was significantly decreased in group 3 compared with group 4.
      CONCLUSIONS: EMF exposure may have potential harmful effects on the
      cardiovascular system, as it promotes severe vascular calcification in CKD
      miliue.

PMID- 24882373
TI  - Anti-inflammatory effect of Natterins, the major toxins from the Thalassophryne
      nattereri fish venom is dependent on TLR4/MyD88/PI3K signaling pathway.
AB  - Here we evaluated whether Natterins affect the leukocyte-endothelial cell
      interaction, hampering leukocyte mobilization and extravasation. Leukocyte
      endothelial cell interactions were evaluated in venules of mouse cremaster muscle
      using intravital microscopy. We reported that low doses of Natterins interfere
      with the cell capturing, inhibiting the interaction of blood neutrophils with the
      post-capillary venules induced by the TLR4 agonist LPS, or the chemokine KC.
      Using endotoxemic mice challenged with LPS, we confirmed that Natterins reduce
      neutrophil accumulation in the peritoneum exudates. The rolling of leukocytes
      induced by KC or LPS was not impaired in Natterins-treated TLR2, MyD88 deficient
      or TLR4 mutant mice, indicating that TLR2- or TLR4-MyD88-mediated signals are
      required for the anti-inflammatory effect of Natterins. The inhibitory effect was
      not influenced by endogenous regulators of inflammation such as IL-10,
      corticosteroids, the HO-1 or the antagonist of the receptor of IL-1, nor by the
      disruption of their proteolytic activity. However, it was completely dependent on
      the activation of serine/threonine phosphatases and the PI3K signaling pathway,
      but independent on increased proteasome activity. This work started asking how
      the main toxins in the T nattereri venom contributes for the deficient influx of
      inflammatory leukocytes, which consequently drive to the delayed inflammatory
      reaction finalization in injured tissue; and finished demonstrating that
      Natterins can control the leukocyte-endothelial wall interactions in a mechanism
      dependent on negative signals derived from TLR2-TLR4/Myd88 signaling cascade.
      Interestingly, we confirmed that the antagonist effect of Natterins is mediated
      by the activation of serine/threonine phosphatases and by the key signaling PI3K
      molecule. 

PMID- 24882372
TI  - Oropharyngeal dysphagia is a prevalent risk factor for malnutrition in a cohort
      of older patients admitted with an acute disease to a general hospital.
AB  - BACKGROUND & AIMS: Oropharyngeal dysphagia and malnutrition are prevalent
      conditions in the older. The aim of this study was to explore the relationship
      between oropharyngeal dysphagia, nutritional status and clinical outcome in older
      patients admitted to an acute geriatric unit. METHODS: We studied 1662 patients
      >=70 years consecutively hospitalized with acute diseases, in whom dysphagia
      could be clinically assessed by the volume-viscosity swallow test and nutritional
      status with the Mini Nutritional Assessment((r)). Anthropometric and laboratory
      measurements were taken and mortality recorded during hospital stay, at 6 months
      and one year after discharge was recorded. RESULTS: 47.4% (95% CI 45-49.8%)
      patients presented oropharyngeal dysphagia and 30.6% (95% CI 27.9%-33.3%),
      malnutrition. Both conditions were associated with multimorbidity, multiple
      geriatric syndromes and poor functional capacity (p < 0.001). However, patients
      with dysphagia presented increased prevalence of malnutrition (MNA((r)) < 17
      45.3% vs 18%, p < 0.001) regardless of their functional status and comorbidities
      (OR 2.31 (1.70-3.14)) and lower albumin and cholesterol levels. Patients with
      malnutrition presented an increased prevalence of dysphagia (68.4% (95% CI 63.3
      73.4)). Patients with dysphagia and patients with malnutrition presented
      increased intrahospital, 6-month and 1-year mortality rates (p < 0.05). The
      poorest outcome was for patients with both conditions (1-year mortality was
      65.8%). CONCLUSIONS: Prevalence of dysphagia was higher than malnutrition in our
      older patients. Dysphagia was an independent risk factor for malnutrition, and
      both conditions were related to poor outcome.

PMID- 24882374
TI  - A rare case of biliary duct obstruction.

PMID- 24882375
TI  - Determination of grayanotoxins in honey by liquid chromatography tandem mass
      spectrometry using dilute-and-shoot sample preparation approach.
AB  - A simple and rugged method of analysis for grayanotoxins I and III in honey using
      liquid chromatography triple quadrupole mass spectrometry with electrospray
      ionization was developed. This paper describes the first LC-MS/MS method for the
      quantitation and confirmation of the grayanotoxins in honey using "dilute-and
      shoot" sample preparation approach. Honey sample was diluted 10-fold in methanol
      water (1:4 v/v) prior to analysis. Chromatographic separation was achieved on a
      reversed phase HPLC column using a water-methanol gradient with 0.1% acetic acid.
      The method was fully validated for quantitative purposes. Overall recoveries,
      selectivity, overall intraday and interday repeatability, decision limit, and
      detection capability of the analytes was determined. The matrix effects,
      ruggedness, and analyte stability in standards and samples were studied. Ten real
      honey samples were successfully analyzed using the developed method. All the
      samples were found to contain residues of GTXs ranging from 0.1 to 39 mg/kg. 

PMID- 24882377
TI  - Plant cytokinesis is orchestrated by the sequential action of the TRAPPII and
      exocyst tethering complexes.
AB  - Plant cytokinesis is initiated in a transient membrane compartment, the cell
      plate, and completed by a process of maturation during which the cell plate
      becomes a cross wall. How the transition from juvenile to adult stages occurs is
      poorly understood. In this study, we monitor the Arabidopsis transport protein
      particle II (TRAPPII) and exocyst tethering complexes throughout cytokinesis. We
      show that their appearance is predominantly sequential, with brief overlap at the
      onset and end of cytokinesis. The TRAPPII complex is required for cell plate
      biogenesis, and the exocyst is required for cell plate maturation. The TRAPPII
      complex sorts plasma membrane proteins, including exocyst subunits, at the cell
      plate throughout cytokinesis. We show that the two tethering complexes physically
      interact and propose that their coordinated action may orchestrate not only plant
      but also animal cytokinesis.

PMID- 24882378
TI  - Parental psychological distress and children's mental health: results of a
      national survey.
AB  - OBJECTIVE: Questions persist as to which dimensions of child mental health are
      most associated with parental mental health status and if these associations
      differ by parental gender. We assessed associations between parental
      psychological distress and children's mental health. METHODS: Pooled data from
      the 2001, 2002, and 2004 National Health Interview Surveys (NHIS), a nationally
      representative, cross-sectional survey of US children aged 4 to 17 (n = 21,314),
      were used. Multivariate logistic regression was performed assessing associations
      between parental psychological distress, measured by the Kessler 6 scale, and the
      extended-form Strengths and Difficulties Questionnaire (SDQ) scales. RESULTS:
      Logistic regression demonstrated associations between parental psychological
      distress and increased likelihood of child mental health problems. Children aged
      4 to 11 were more likely to have mental health problems if they had a
      psychologically distressed father (odds ratio [OR] 7.5, 95% confidence interval
      [CI] 2.3-24.3) or mother (OR 6.7, 95% CI 2.7-16.7). Children aged 12 to 17 with a
      psychologically distressed father (OR 4.53, 95% CI 1.18-17.47) or mother (OR
      3.90, 95% CI 1.34-11.37) were also more likely than those without to have mental
      health problems. In parents of both genders, associations existed between
      parental psychological distress, and abnormal emotional symptoms in younger
      children, conduct disorder in older children, and hyperactivity in children of
      all ages. CONCLUSIONS: Parental psychological distress appears similarly
      associated with adverse child mental health outcomes, regardless of parental
      gender. These findings corroborate limited prior research and demonstrate that
      associations between child mental health and parental mental illness are similar
      in magnitude for fathers and mothers.

PMID- 24882376
TI  - A role for retrotransposon LINE-1 in fetal oocyte attrition in mice.
AB  - Fetal oocyte attrition (FOA) is a conserved but poorly understood process of
      elimination of more than two-thirds of meiotic prophase I (MPI) oocytes before
      birth. We now implicate retrotransposons LINE-1 (L1), activated during epigenetic
      reprogramming of the embryonic germline, in FOA in mice. We show that wild-type
      fetal oocytes possess differential nuclear levels of L1ORF1p, an L1-encoded
      protein essential for L1 ribonucleoprotein particle (L1RNP) formation and L1
      retrotransposition. We demonstrate that experimental elevation of L1 expression
      correlates with increased MPI defects, FOA, oocyte aneuploidy, and embryonic
      lethality. Conversely, reverse transcriptase (RT) inhibitor AZT has a profound
      effect on the FOA dynamics and meiotic recombination, and it implicates an RT
      dependent trigger in oocyte elimination in early MPI. We propose that FOA serves
      to select oocytes with limited L1 activity that are therefore best suited for the
      next generation.

PMID- 24882380
TI  - Soft tissue giant cell tumor of low malignant potential with 3 localizations:
      report of a case.
AB  - Soft tissue giant cell tumor (GCT-ST) of low malignant potential, also called
      primary giant cell tumor of soft tissue, is usually located in the lower
      extremities and trunk, whereas it is extremely rare in the head and neck region.
      It is a rare neoplasm involving both superficial and deep soft tissues that
      mainly affects young to middle-aged adults, presenting as an asymptomatic, well
      circumscribed multinodular mass covered by normal skin or with a fleshy red-brown
      surface when superficially located. The purpose of this article is to report a
      case of osteoclast-like giant cell tumors of the lip and to review the literature
      about GCT-STs involving the head and neck region. 

PMID- 24882379
TI  - Identifying sickle cell disease cases using administrative claims.
AB  - OBJECTIVE: To develop and test the accuracy of administrative claims method for
      identifying children with sickle cell disease (SCD) to enable quality of care
      assessments among children enrolled in Medicaid. METHODS: All administrative
      claims with an SCD diagnosis were obtained from Michigan Medicaid from 2008 to
      2011 for children <=18 years, representing 1828 individuals. All Medicaid claims
      were obtained for these children and classified into categories on the basis of
      SCD care; these classifications were used to develop 37 alternative case
      definitions for identifying children with SCD. Children with >=1 SCD claim in
      2010 or 2011 were identified as confirmed SCD or not SCD using the gold standard
      of Michigan newborn screening administrative records. Measures of performance
      were calculated for each case definition for eligible children in 2010. Further
      validation of the case definitions was performed among eligible children in 2011.
      RESULTS: In 2010, a total of 938 children met eligibility criteria and were
      linked to newborn screening records; 605 (59%) were confirmed SCD, and 333 (32%)
      were not SCD. Measures of performance varied among the 37 case definitions, and
      the 4 best case definitions on the basis of the sensitivity, specificity, and
      area under the receiver operating characteristic (ROC) curve were validated among
      924 children meeting eligibility criteria in 2011. The case definition of at
      least 3 SCD claims in any position identified children with SCD with the most
      accuracy, with an area under the ROC curve of 0.91 (95% confidence interval 0.89,
      0.93). CONCLUSIONS: This definition can be used to facilitate a more accurate
      identification of children with SCD in future studies. Further investigation is
      necessary to determine whether this method translates to other populations
      besides Michigan Medicaid-insured children.

PMID- 24882381
TI  - Nab-paclitaxel and gemcitabine for the treatment of patients with metastatic
      pancreatic cancer.
AB  - Adenocarcinoma of the pancreas or pancreatic cancer as we will refer to it here,
      is a cancer of poor prognosis with a high mortality, particularly in the advanced
      or metastatic setting. Until 2011 and the Phase III results of FOLFIRINOX,
      standard treatment options were limited to gemcitabine. Combination therapy had
      shown either a lack of or very limited improvement versus monotherapy with
      gemcitabine. With the positive results of the MPACT study in 2013 showing
      improved survival with nab-paclitaxel plus gemcitabine combination therapy, there
      are now more options for oncologists to treat patients with advanced pancreatic
      cancer. This paper will highlight the Phase I/II and Phase III trials of nab
      paclitaxel plus gemcitabine along with discussing their biology and further
      possible development in treating patients with pancreatic cancer. 

PMID- 24882382
TI  - Increased skeletal muscle expression of the endoplasmic reticulum chaperone GRP78
      in patients with myasthenia gravis.
AB  - In myasthenia gravis (MG), damage to neuromuscular junctions may induce
      endoplasmic reticulum (ER) stress in skeletal muscles. In the current study,
      skeletal muscles obtained from patients with MG exhibited upregulation of glucose
      regulated protein 78 (GRP78) mRNA that was activated by ER stress. Furthermore,
      GRP78 mRNA expression was higher in patients with MG and myositis than in
      patients with non-myopathy. We also observed a significant positive correlation
      between GRP78 mRNA expression and GRP78 protein levels and between GRP78 mRNA
      expression and age of MG onset. Our findings suggest that muscle weakness in MG
      might be caused by both neuromuscular junction disruption and ER stress.

PMID- 24882384
TI  - Efficacy of phase 1 trials in malignant pleural mesothelioma: description of a
      series of patients at a single institution.
AB  - BACKGROUND: Malignant pleural mesothelioma (MPM) is a locally aggressive disease
      with a poor prognosis. After failure of first line platinum-based chemotherapy,
      there is no widely approved salvage regimen. New strategies for treatment are
      needed and phase 1 trials appear as a rationale alternative. MATERIALS AND
      METHODS: MPM patients were enrolled in 20 different phase 1 trials between March
      2005 and January 2012, and their data analyzed retrospectively. The primary
      endpoint was response rate and secondary endpoints were toxicity profile, overall
      survival (OS) and progression free survival (PFS). OS and PFS were estimated
      using Kaplan-Meier and their association with baseline characteristics was
      investigated through a log-rank test. The drugs described were divided into 5
      groups based on their mechanism of action. RESULTS: Forty-five patients were
      analyzed with a median follow up of 20.5 months. The best tumor response was as
      follows: 4% of patients had a RECIST partial response, 60% had stable disease,
      24% had progressive disease and 11% were not evaluable. Grade >=3 toxicities were
      observed in 19 (42%) patients. Median OS and PFS were estimated to 6 months (95%
      CI=[4.2-10.5]) and 2 months (95% CI=[1.3-2.7]), respectively. The cellular
      motility inhibitors group appeared as the most promising class to be developed in
      a phase 2 setting. CONCLUSION: Including MPM patients in phase I trials beyond
      first line of treatment can result in modest clinical benefits with an acceptable
      toxicity profile. Several molecular pathways involved in MPM have been identified
      and further novel biologic therapies need to be tested.

PMID- 24882383
TI  - Prognostic value of circulating tumor cells' reduction in patients with extensive
      small-cell lung cancer.
AB  - OBJECTIVES: Circulating tumor cells (CTCs) have been hypothesized to be a
      prognostic factor in small-cell lung cancer (SCLC), and different cutoffs have
      been proposed to identify patients at high risk. We assessed the prognostic value
      of CTCs in patients with extensive SCLC. MATERIALS AND METHODS: CTCs were
      assessed with the CellSearch system in 60 extensive SCLC patients. CTC count at
      baseline or after one cycle of chemotherapy (cycle-1) or as change after
      chemotherapy were analyzed separately. Primary outcome was overall survival. The
      accuracy of prognostic role was assessed by Harrell's c-index. "Optimal" cutoffs
      were derived by bootstrap resampling to reduce the overfitting bias; accuracy
      improvement was estimated by calculating the difference of c-indexes of models
      including clinical variables with or without CTCs. RESULTS: CTCs were identified
      in 90% (54/60) of patients at baseline, in which CTC count ranged from 0 to
      24,281. CTC count was strongly associated with the number of organs involved. The
      prognostic accuracy was only marginally increased by the addition to clinical
      information of "optimal" CTC cutoffs at baseline and after cycle-1. Conversely, a
      reduction of CTC count higher than 89% following chemotherapy significantly
      improved prognostic accuracy (bootstrap p-value=0.009) and was associated with a
      lower risk of death (HR 0.24, 95% CI 0.09-0.61). When previously proposed cutoffs
      were applied to our cohort, they showed only marginal improvement of the
      prognostic accuracy. CONCLUSION: CTCs have useful prognostic role in extensive
      SCLC, but only the change of CTC count after the first cycle of chemotherapy
      provides clinically relevant information. Previously reported CTC cutoffs were
      not prognostic in our cohort of patients.

PMID- 24882385
TI  - Prophylactic use of mTOR inhibitors and other immunosuppressive agents in heart
      transplant patients.

PMID- 24882386
TI  - Effect of everolimus on the immunomodulation of the human neutrophil inflammatory
      response and activation.
AB  - The primary cause of mortality at 5 years following a cardiac transplantation is
      the development of atherosclerosis, termed coronary allograft vasculopathy (CAV).
      This pathology is characterized by diffused intimal hyperplasia and emanates from
      coronary arterial injuries caused by immune inflammatory cells. Neutrophils play
      an important role in this inflammatory process; however, their potential
      participation in the pathogenesis of CAV is poorly understood. Despite their
      essential contribution to the prevention of graft rejection, immunosuppressive
      drugs could have detrimental effects owing to their pro-inflammatory activities.
      Thus, we investigated the impact of different immunosuppressive drugs on the
      inflammatory response of neutrophils isolated from the blood of healthy
      volunteers. Under basal conditions, mammalian target of rapamycin (mTOR)
      inhibitors (sirolimus and everolimus) had the most potent anti-inflammatory
      effect, decreasing both IL-8 release (~-80%) and vascular endothelial growth
      factor (VEGF) release (~-65%) and preserving the release of the anti-inflammatory
      cytokine interleukin-1 receptor antagonist (IL-1RA). In TNF-alpha-treated
      neutrophils, pre-incubation with everolimus provided the most potent effect,
      simultaneously reducing the release of both VEGF and IL-8 while doubling the
      release of IL-1RA. This latter effect of everolimus was maintained even when
      administered in combination with other immunosuppressive drugs. Sirolimus and
      everolimus decreased the tumor necrosis factor (TNF)-alpha-induced adhesion of
      neutrophils to human endothelial cells and human extracellular matrix. This
      effect was largely dependent on the ability of these compounds to alter beta2
      integrin/CD18 activation. Our results suggest a potential mechanism for the
      beneficial effect of everolimus in the prevention of CAV in heart transplant
      recipients. 

PMID- 24882387
TI  - Stretch-induced human myometrial cytokines enhance immune cell recruitment via
      endothelial activation.
AB  - Spontaneous term labour is associated with amplified inflammatory events in the
      myometrium including cytokine production and leukocyte infiltration; however,
      potential mechanisms regulating such events are not fully understood. We
      hypothesized that mechanical stretch of the uterine wall by the growing fetus
      facilitates peripheral leukocyte extravasation into the term myometrium through
      the release of various cytokines by uterine myocytes. Human myometrial cells
      (hTERT-HM) were subjected to static mechanical stretch; stretch-conditioned media
      was collected and analysed using 48-plex Luminex assay and ELISA. Effect of
      stretch-conditioned media on cell adhesion molecule expression of human uterine
      microvascular endothelial cells (UtMVEC-Myo) was detected by quantitative
      polymerase chain reaction (qPCR) and flow cytometry; functional assays testing
      leukocyte-endothelial interactions: adhesion of leukocytes to endothelial cells
      and transendothelial migration of calcein-labelled primary human neutrophils as
      well as migration of THP-1 monocytic cells were assessed by fluorometry. The
      current in vitro study demonstrated that mechanical stretch (i) directly induces
      secretion of multiple cytokines and chemokines by hTERT-HM cells (IL-6, CXCL8,
      CXCL1, migration inhibitory factor (MIF), VEGF, G-CSF, IL-12p70, bFGF and
      platelet-derived growth factor subunit B (PDGF-bb), P<0.05); stretch-induced
      cytokines (ii) enhance leukocyte adhesion to the endothelium of the surrounding
      uterine microvasculature by (iii) inducing the expression of endothelial cell
      adhesion molecules and (iv) directing the transendothelial migration of
      peripheral leukocytes. (vi) Chemokine-neutralizing antibodies and broad-spectrum
      chemokine inhibitor block leukocyte migration. Our data provide a proof of
      mechanical regulation for leukocyte recruitment from the uterine blood vessels to
      the myometrium, suggesting a putative mechanism for the leukocyte infiltrate into
      the uterus during labour and postpartum involution. 

PMID- 24882388
TI  - Radiation-induced apoptosis varies among individuals and is modified by sex and
      age.
AB  - PURPOSE: Although there are considerable data on mechanisms of radiation-induced
      apoptosis in vitro and in animal models, little is known about functional
      variation in these pathways in humans. We sought to develop a tractable system to
      evaluate this. MATERIALS AND METHODS: Peripheral blood mononuclear cells were
      isolated from 90 healthy volunteers, divided into two aliquots, one irradiated
      with a 5 Gy dose and the other sham-treated (0 Gy), and assessed for damage
      induced apoptosis after 24 hours. To investigate reproducibility, 10 individuals
      spanning the entire radiation-induced apoptotic range were tested three times
      each, with 3-6 months between replicates. RESULTS: We observed surprising
      heterogeneity in apoptosis among individuals, ranging from 21-62%. Biological
      replicates from a single individual, however, were completely concordant,
      suggesting the variability observed across individuals is not the result of
      stochastic or short-term effects. We found significantly higher radiation-induced
      apoptosis in males than in females (Mean: 41.0% vs. 30.7%; p < 3.5 * 10(-7)).
      Moreover, advancing age was associated with decreasing radiation-induced
      apoptosis in males (p = 0.01) but not females (p = 0.82). CONCLUSIONS: Our
      results provide evidence that the function of cellular pathways crucial for
      stress-induced apoptosis varies by sex and could decline with age in humans.

PMID- 24882389
TI  - Long-term cognitive effects of human stem cell transplantation in the irradiated
      brain.
AB  - PURPOSE: Radiotherapy remains a primary treatment modality for the majority of
      central nervous system tumors, but frequently leads to debilitating cognitive
      dysfunction. Given the absence of satisfactory solutions to this serious problem,
      we have used human stem cell therapies to ameliorate radiation-induced cognitive
      impairment. Here, past studies have been extended to determine whether engrafted
      cells provide even longer-term benefits to cognition. MATERIALS AND METHODS:
      Athymic nude rats were cranially irradiated (10 Gy) and subjected to
      intrahippocampal transplantation surgery 2 days later. Human embryonic stem cells
      (hESC) or human neural stem cells (hNSC) were transplanted, and animals were
      subjected to cognitive testing on a novel place recognition task 8 months later.
      RESULTS: Grafting of hNSC was found to provide long lasting cognitive benefits
      over an 8-month post-irradiation interval. At this protracted time, hNSC grafting
      improved behavioral performance on a novel place recognition task compared to
      irradiated animals not receiving stem cells. Engrafted hESC previously shown to
      be beneficial following a similar task, 1 and 4 months after irradiation, were
      not found to provide cognitive benefits at 8 months. CONCLUSIONS: Our findings
      suggest that hNSC transplantation promotes the long-term recovery of the
      irradiated brain, where intrahippocampal stem cell grafting helps to preserve
      cognitive function.

PMID- 24882390
TI  - Synergestic effect of aqueous purslane (Portulaca oleracea L.) extract and fish
      oil on radiation-induced damage in rats.
AB  - PURPOSE: To evaluate the impact of oral administration of purslane (Portulaca
      oleracea) extract or fish oil and their co-treatments in the modulation of
      radiation-induced damage. MATERIAL AND METHODS: Purslane (P) (400 mg/kg body
      weight) or fish oil (Fo) (60 mg/kg body weight) was administrated to male albino
      rats via gastric intubation for 15 days after whole body exposure to a single
      dose of 6 Gy gamma rays. The animals were sacrificed after the elapse of 15 days.
      RESULTS: The results revealed that irradiation induced a significant elevation of
      total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol
      (LDL-c), and atherogenic index: TC/high density lipoprotein cholesterol (HDL-c)
      in addition to aspartate and alanine transaminase (AST, ALT), alkaline phophatase
      (ALP), bilirubin, as well as urea, creatinine and uric acid. Moreover, liver,
      kidney and heart malondialdehyde (MDA) was significantly elevated, whereas nitric
      oxide (NO), superoxide dismutase (SOD), catalase (CAT) and HDL-c were depressed.
      Purslane and/or fish oil treatment significantly attenuated lipids alteration,
      liver and kidney functions as well as oxidative stress in irradiated rats. The
      results pointed out that dietary fish oil supplementation, at adequate doses, may
      provide a cushion for a prolonged therapeutic option against radiation-induced
      damage without harmful side-effects. CONCLUSION: It could be concluded that
      purslane extract and fish oil may have therapeutic potential to improve hepatic
      and renal functions as well as oxidative stress in irradiated rats. Moreover,
      their co-administration showed a better improved liver function.

PMID- 24882391
TI  - Carbon ion beam is more effective to induce cell death in sphere-type A172 human
      glioblastoma cells compared with X-rays.
AB  - PURPOSE: To obtain human glioblastoma cells A172 expressing stem cell-related
      protein and comparison of radiosensitivity in these cells with X-rays and carbon
      beam. METHODS: Human monolayer-type A172 glioblastoma cells were maintained in
      normal medium with 10% bovine serum. In order to obtain sphere-type A172 cells
      the medium was replaced with serum-free medium supplemented with growth factors.
      Both types of A172 cells were irradiated with either X-rays or carbon ion beams
      and their radiosensitivity was evaluated. RESULTS: Serum-free medium induced
      expression of stem cell-related proteins in A172 cells along with the neurosphere
      like appearance. These sphere-type cells were found resistant to both X-rays and
      carbon ion beams. Phosphorylation of histone H2A family member X persisted for a
      longer period in the cells exposed to carbon ion beams than in those exposed to X
      rays and it disappeared quicker in the sphere type than in the monolayer type.
      Relative radioresistance of the sphere type cells was smaller for carbon ion
      beams than for X-rays. CONCLUSIONS: We demonstrated that glioblastoma A172 cells
      with induced stem cell-related proteins turned resistant to irradiation.
      Accelerated heavy ion particles may have advantage over X-rays in overcoming the
      tumor resistance due to cell stemness.

PMID- 24882392
TI  - Carbamazepine-induced cutaneous reactions: a simple assay to identify patients
      carrying the HLA-A*31:01 allele.
AB  - AIMS: Treatment with the first-line antiepileptic drug, carbamazepine (CBZ), is
      associated with adverse cutaneous reactions in up to 10% of patients. One
      predisposition to these side-effects has been linked to the HLA-A*31:01 allele.
      HLA-typing is costly and time-consuming. A single nucleotide polymorphism (SNP,
      rs1061235A > T) has been suggested as a marker for the HLA-A*31:01 allele. We
      sought to develop and validate a simple, fast and inexpensive assay for rs1061235
      to apply in the Norwegian population. METHODS: We designed a polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP) assay for the SNP
      and tested it on a set of 16 samples with known HLA-A alleles. RESULTS: The assay
      identified all HLA-A*31:01 alleles present, but also marked for HLA-A*33:03. In a
      second set of 204 samples from Norwegian epilepsy patients with unknown HLA
      alleles, nine samples heterozygous for the rs1061235 were found. Subsequent HLA
      typing showed that one sample was HLA-A*33:01, whereas the other eight were
      identified as HLA-A*31:01. The remaining 195 samples were correctly identified as
      neither carrying the rs1061235 SNP nor HLA-A*31:01. The sensitivity and
      specificity of the rs1061235 SNP test was 100% and 99.5%, respectively.
      Misinterpretation of the rare HLA-A*33 variants as HLA-A*31:01 has minor
      consequence, as it only would result in choosing an alternative drug to CBZ.
      CONCLUSION: We have designed and validated a simple, fast and inexpensive test
      for the rs1061235A> T SNP as a marker for HLA-A*31:01 in the Norwegian population
      for potential use in a personalized treatment approach to patients planned to
      receive CBZ.

PMID- 24882393
TI  - [Cardiovascular safety of non-insulin anti-diabetic drugs. Scientific position
      statement of SEMERGEN].
AB  - Diabetes increases the risk of both microvascular and macrovascular
      complications. Although reducing plasma glucose levels to recommended targets
      decreases the risk of microvascular outcomes, the effects of anti-diabetic drugs
      on macrovascular complications and cardiovascular death are of concern. In fact,
      it has been suggested that some anti-diabetic agents could even be harmful for
      cardiovascular outcomes. In this context, several health care regulatory agencies
      have established the need for performing clinical trials specifically designed to
      assess the cardiovascular safety of anti-diabetic drugs. The results of 2
      clinical trials have recently been published that provide important information
      on the cardiovascular safety of dipeptidyl peptidase 4 (DPP-4) inhibitors. The
      aim of this document was to review the available evidence on the cardiovascular
      safety of non-insulin anti-diabetic drugs and provide practical recommendations
      on their use in this context. 

PMID- 24882394
TI  - Biological monitoring to assess dermal exposure to ethylene oxide vapours during
      an incidental release.
AB  - During a short incident in an ethylene oxide (EO) producing plant, EO vapour was
      released under high pressure. Operators wore full respiratory protection during
      repairs to fix the leak. To check the adequacy of the applied personal protective
      equipment and to address concerns about potential dermal exposure and subsequent
      uptake of EO, biological monitoring was applied by determination of the
      haemoglobin adducts of EO in blood. Based on the results of the biomonitoring, a
      risk assessment of dermal exposure to EO vapour was made. Calculations to
      estimate dermal exposure, based on two recently published models and using the
      relevant physical-chemical properties of EO, indicate that the dermal
      contribution to total exposure is expected to be negligible under normal
      operating circumstances. However, the models indicate that under accidental
      circumstances of product spillage, when high air concentrations can build up
      quickly and where incident response is conducted under respiratory protection
      with independently supplied air, the systemic exposure resulting from dermal
      absorption may reach levels of concern. The model estimates were compared to the
      actual biomonitoring data in the operators involved in the accidental release of
      EO vapour. The results suggest that when incidental exposures to high EO vapour
      concentrations (several thousand ppm) occur during periods in excess of 20-30
      min, additional risk management measures, such as wearing chemical impervious
      suits, should be considered to control dermal uptake of EO.

PMID- 24882396
TI  - Indacaterol in the Treatment of Chronic Obstructive Pulmonary Disease: From
      Clinical Trials to Daily Practice.
AB  - Indacaterol was introduced as an agent of the new generation of very long acting
      beta2-agonists (VLABA) that provides a 24-hour activity of bronchodilation and
      allows a once-daily OD dosing. The first trial showed a significantly higher
      efficacy of indacaterol vs. placebo in patients with chronic obstructive
      pulmonary disease (COPD). The following trials were aimed at evaluating its
      performance compared with other bronchodilators. The results can be summarized in
      a comparable efficacy of indacaterol, mainly assessed by the increase in FEV1
      value but also by quality of life and other patient- reported outcomes (PROs),
      compared with the OD antimuscarinic tiotropium bromide, and in a slightly higher
      efficacy compared with the LABA formoterol and salmeterol administered twice
      daily. No problems of safety and tolerability were reported in the trials as well
      as in specific studies, every kind of adverse event, including cardiovascular
      effects, being similarly frequent with indacaterol and with placebo. Concerning
      the real-life management, in respect to LABA, the OD dosing makes indacaterol
      more convenient for COPD patients and is likely to positively influence the
      patient's adherence. Since adherence to medical treatment of chronic diseases,
      and particularly COPD is a crucial issue in medicine, such aspect should confer
      to indacaterol a valuable role in clinical practice. The recently approved
      combination of indacaterol with the antimuscarinic glycopyrronium [QVA149], based
      on the demonstration of positive effects on both lung function and PROs, is
      likely to be a further option for patients with severe COPD. 

PMID- 24882395
TI  - A human monoclonal anti-TNF alpha antibody (adalimumab) reduces airway
      inflammation and ameliorates lung histology in a murine model of acute asthma.
AB  - BACKGROUND: A few experimental studies related to asthma have unveiled the
      beneficial effects of TNF alpha blocking agents on the airway histology, cytokine
      levels in bronchoalveolar lavage and bronchial hyper-responsiveness. In the
      current study, we aimed to assess the effect of adalimumab on the inflammation
      and histology of asthma in a murine model. METHOD: Twelve-week-old BALB/c (H
      2d/d) female rats (n=18) were allocated into three groups, including (group I)
      control (phosphate-buffered saline was implemented), (group II) asthma induced
      with OVA (n=6), and (group III) asthma induced with OVA+treated with adalimumab
      (n=6). Rats were executed on the 28th day of the study. The lung samples were
      fixed in 10% neutral buffered formalin. Lung parenchyma, alveolus, peribronchial
      and perivascular inflammation were assessed. Lung pathological scoring was
      performed. RESULT: Severity of lung damage was found to be reduced significantly
      in the asthma induced with OVA+treated with adalimumab group. When compared with
      the untreated group, adalimumab significantly reduced the inflammatory cells
      around the bronchi and bronchioles, and reduced inflammation of the alveolar wall
      and alveolar wall thickness as well (median score=1, p=0.52). Peribronchial
      smooth muscle hypertrophy and oedema were significantly reduced after adalimumab
      administration. CONCLUSION: Adalimumab (a human monoclonal anti-TNF alpha
      antibody) therapy significantly reduced the severity of lung damage by decreasing
      cellular infiltration and improvement on the lung histology in a murine model of
      acute asthma.

PMID- 24882398
TI  - Refractive error change and its association with ocular and general parameters in
      junior high school students in Taiwan.
AB  - PURPOSE: To assess the relationships between refractive error and ocular and
      general parameters in Taiwanese junior high school students and to identify the
      predictive factors associated with the changes in refractive error. METHODS: This
      was a prospective, school-based study. A total of 687 students (357 boys and 330
      girls) from a municipal junior high school in Taipei were enrolled. The students'
      refractive status, intraocular pressure, and ocular parameters were measured
      first in 2010 and again 1 year later. Data were analyzed using multiple linear
      regression models and generalized estimating equations (GEEs). RESULTS:
      Significant differences were found between the baseline (2010) and 1-year follow
      up (2011) mean anterior chamber depths, mean axial lengths, and mean horizontal
      and vertical corneal refractive powers. GEE models revealed that vertical and
      horizontal corneal refractive powers, axial length, and anterior chamber depth
      were significantly associated with refractive error change. CONCLUSIONS: Students
      with a longer axial length, steeper corneal radius, and shallower anterior
      chamber depth had an increased risk of myopic refractive errors.

PMID- 24882399
TI  - Pharmacologically active constituents from plants used in traditional medicine.
      Foreword.

PMID- 24882400
TI  - Search for new type of PPARgamma agonist-like anti-diabetic compounds from
      medicinal plants.
AB  - Potent ligands of peroxisome proliferator-activated receptor gamma (PPARgamma)
      such as thiazolidinediones (pioglitazone, troglitazone, etc.) improve insulin
      sensitivity by increasing the levels of adiponectin, an important adipocytokine
      associated with insulin sensitivity in adipose tissue. Several constituents from
      medicinal plants were recently reported to show PPARgamma agonist-like activity
      in 3T3-L1 cells, but did not show agonistic activity at the receptor site
      different from thiazolidinediones. Our recent studies on PPARgamma agonist-like
      constituents, such as hydrangenol and hydrangeic acid from the processed leaves
      of Hydrangea macrophylla var. thunbergii, piperlonguminine and retrofractamide A
      from the fruit of Piper chaba, and tetramethylkaempferol and pentamethylquercetin
      from the rhizomes of Kaempferia parviflora, are reviewed. 

PMID- 24882397
TI  - Relationship between retinal morphological findings and autoantibody profile in
      primary Sjogren's syndrome.
AB  - PURPOSE: To investigate the morphological changes of the retina measured with the
      Cirrus high-definition optical coherence tomography in patients with primary
      Sjogren's syndrome (pSS). METHODS: One hundred ninety six eyes of 196 patients
      with pSS and 200 eyes of 200 age and sex-matched normal controls were enrolled.
      Patients with pSS were divided into four subgroups based on their presence of
      autoantibodies (antinuclear antibody (ANA), anti-Ro/SSA, and anti-La/SSB).
      Peripapillary retinal nerve fiber layer (pRNFL) thickness, macular ganglion cell
      inner plexiform layer (mGCIPL) thickness, and optic nerve head parameters were
      compared between groups. RESULTS: Compared with controls, a significant decrease
      was observed in the average, inferior, and temporal thicknesses of pRNFL and in
      the minimum, superotemporal, inferonasal, inferior, and inferotemporal
      thicknesses of mGCIPL of eyes with pSS (all P < 0.05). In subgroup analyses, all
      eyes with positive tested autoantibodies [ANA(+), anti-Ro/SSA(+), anti-La/SSB(+)]
      showed a significant decrease of mGCIPL thicknesses, except for the superonasal
      portion, compared with eyes with any positivity for autoantibody (all P < 0.05).
      There was a negative linear relationship between the number of positive
      autoantibodies and average and inferior pRNFL thicknesses or all mGCIPL
      parameters, except for the superonasal portion, with a Spearman correlation
      analysis in patients with pSS (all P < 0.05). CONCLUSIONS: Compared with
      controls, eyes with pSS showed thinning of pRNFL and mGCIPL thicknesses. The
      degree of thinning correlated with increased numbers of the positive
      autoantibody.

PMID- 24882401
TI  - Effects of Ashwagandha (roots of Withania somnifera) on neurodegenerative
      diseases.
AB  - Neurodegenerative diseases commonly induce irreversible destruction of central
      nervous system (CNS) neuronal networks, resulting in permanent functional
      impairments. Effective medications against neurodegenerative diseases are
      currently lacking. Ashwagandha (roots of Withania somnifera Dunal) is used in
      traditional Indian medicine (Ayurveda) for general debility, consumption, nervous
      exhaustion, insomnia, and loss of memory. In this review, we summarize various
      effects and mechanisms of Ashwagandha extracts and related compounds on in vitro
      and in vivo models of neurodegenerative diseases such as Alzheimer's disease and
      spinal cord injury. 

PMID- 24882402
TI  - 3-Monoglucuronyl glycyrrhretinic acid is a possible marker compound related to
      licorice-induced pseudoaldosteronism.
AB  - One of the most common adverse effects of traditional Japanese kampo and
      traditional Chinese medicine is pseudoaldosteronism caused by licorice. In this
      review, the authors describe the mechanisms of licorice-induced
      pseudoaldosteronism by the pharmacokinetics of chemical constituents and its
      metabolites containing licorice. Glycyrrhizin (GL), the main constituent of
      licorice, is absorbed as glycyrrhetinic acid (GA), which is a metabolite of GL
      produced by enterobacteria before its release into the circulation. Circulating
      GA is metabolized in the liver to become 3-monoglucuronyl-glycyrrhetinic acid
      (3MGA), which is excreted into the bile via multidrug resistance protein 2
      (Mrp2). If Mrp2 function is damaged for some reason, 3MGA is secreted from the
      liver into the circulation, and excreted into the urine via organic anion
      transporters expressed at the basolateral side of tubular epithelial cells.
      Circulating GA cannot be excreted into the urine since GA binds highly to serum
      albumin and thus does not pass through glomerular filtration and is not a
      substrate of transporters expressed on tubular epithelial cells. Licorice-induced
      pseudoaldosteronism develops due to the inhibition of type 2 11beta-hydrosteroid
      dehydrogenase (11beta-HSD2) which results in the accumulation of cortisol in
      tubular epithelial cells that activate mineral corticoid receptors to stimulate
      the excretion of potassium that results in hypokalemia. GA, unlike 3MGA, cannot
      pass through tubular epithelial cells and cannot inhibit the enzyme in the cells.
      Therefore, 3MGA may be a genuine causative agent for licorice-induced
      pseudoaldosteronism. When licorice is used, 3MGA in plasma or urine could
      function as a marker compound to prevent the adverse effects. 

PMID- 24882403
TI  - Prospecting for bioactive constituents from traditional medicinal plants through
      ethnobotanical approaches.
AB  - Pharmacologically active constituents from traditional medicinal plants have
      received great attention as sources of novel agents, pharmaceutical
      intermediates, and chemical entities for synthetic or semisynthetic drugs due to
      their potent pharmacological activities, low toxicity, and economic viability.
      Numerous components have been isolated from traditional medicinal plants,
      including alkaloids, flavonoids, and terpenoids, and clinical and experimental
      studies suggested that these components have useful pharmacological properties
      such as antiinfectious, antioxidative, and antiinflammatory effects. In this
      review, modern ethnobotanical approaches to explore folk medicinal plants as
      candidates for drug discovery with the greatest possibility of success are
      discussed. Determining the bioactive mechanisms and tracing structure-activity
      relationships will promote the discovery of new drugs and pharmacological agents.

PMID- 24882404
TI  - Developing population pharmacokinetic parameters for high-dose methotrexate
      therapy: implication of correlations among developed parameters for individual
      parameter estimation using the Bayesian least-squares method.
AB  - Bayesian estimation enables the individual pharmacokinetic parameters of the
      medication administrated to be estimated using only a few blood concentrations.
      Due to wide inter-individual variability in the pharmacokinetics of methotrexate
      (MTX), the concentration of MTX needs to be frequently determined during high
      dose MTX therapy in order to prevent toxic adverse events. To apply the benefits
      of Bayesian estimation to cases treated with this therapy, we attempted to
      develop an estimation method using the Bayesian least-squares method, which is
      commonly used for therapeutic monitoring in a clinical setting. Because this
      method hypothesizes independency among population pharmacokinetic parameters, we
      focused on correlations among population pharmacokinetic parameters used to
      estimate individual parameters. A two-compartment model adequately described the
      observed concentration of MTX. The individual pharmacokinetic parameters of MTX
      were estimated in 57 cases using the maximum likelihood method. Among the
      available parameters accounting for a 2-compartment model, V1, k10, k12, and k21
      were found to be the combination showing the weakest correlations, which
      indicated that this combination was best suited to the Bayesian least-squares
      method. Using this combination of population pharmacokinetic parameters, Bayesian
      estimation provided an accurate estimation of individual parameters. In addition,
      we demonstrated that the degree of correlation among population pharmacokinetic
      parameters used in the estimation affected the precision of the estimates. This
      result highlights the necessity of assessing correlations among the population
      pharmacokinetic parameters used in the Bayesian least-squares method. 

PMID- 24882405
TI  - Adenosine 3',5'-cyclic monophosphate involvement in hepatic triacylglyceride
      lipase release from prazosin-stimulated primary cultured rat hepatocytes.
AB  - We recently found that hepatic triglyceride lipase (HTGL) was released from
      primary cultured rat hepatocytes after treatment with prazosin, an antagonist of
      alpha-1 adrenoceptors. However, the details of prazosin-induced HTGL release
      remain uncertain. Here we investigated whether changes in cAMP levels in
      hepatocytes were related to HTGL release from prazosin-stimulated hepatocytes.
      When hepatocytes were treated with prazosin, cAMP levels during stimulated
      release of HTGL increased in a time- and dose-dependent manner. Stimulated
      release of HTGL was suppressed by the adenylate cyclase inhibitors MDL-12,330A
      and 2',5'-dideoxyadenosine. Further, cAMP-dependent protein kinase A (PKA)
      activity in prazosin-stimulated hepatocytes also increased in a time- and dose
      dependent manner. Moreover, prazosin-stimulated HTGL release was suppressed by
      the PKA inhibitors H-89 and KT5720. These results suggest that prazosin
      stimulated HTGL release from hepatocytes was due to cAMP production and partly
      due to subsequent PKA activation in hepatocytes. 

PMID- 24882406
TI  - Development and evaluation of optimized sucrose ester stabilized oleanolic acid
      nanosuspensions prepared by wet ball milling with design of experiments.
AB  - The aim of this study was to develop optimized sucrose ester (SE) stabilized
      oleanolic acid (OA) nanosuspensions (NS) for enhanced delivery via wet ball
      milling by design of experiments (DOE). In this study, SEOA NS batches were
      prepared by wet ball milling method. Mean particle sizes and polydispersity
      indices were determined using a nanosizer. The percent encapsulation efficiency,
      saturation solubility and in vitro dissolution rate were obtained with analyses
      using HPLC. Preparation methods were optimized by DOE using the Minitab software.
      The in vitro bioefficacy was obtained by methyl thiazolyl tetrazolium (MTT)
      measurements in A549 human non small cell lung cancer cell line. The in vivo
      pharmacokinetics profile was determined using LC-electrospray ionization (ESI)
      MS/MS. The study produced spherical SEOA NS particles (ca. 100 nm in diameter)
      which were found to be able to increase OA saturation solubility considerably.
      Optimized SEOA-GBD NS (milled at 600 rpm for 3 h, sucrose monolaurate (SEL) :
      sucrose monopalmitate (SEP) at 9 : 1, w/w; SE : OA at 1 : 1, w/w) was found to be
      physically stable over 14 d at 4 degrees C. The NS showed much higher dissolution
      rate, cytotoxicity and bioavailability when compared with the free drug. Thus,
      the prepared OA as SE stabilized NS particles by wet ball milling enhanced the
      saturation solubility, in vitro dissolution rate, bioefficacy and in vivo
      bioavailability of OA. The use of sugar esters may also be potentially applied to
      other hydrophobic drugs. 

PMID- 24882408
TI  - Danshensu inhibits beta-adrenergic receptors-mediated cardiac fibrosis by ROS/p38
      MAPK axis.
AB  - Danshensu, the effective ingredient of the plant Salvia miltiorrhiza (Danshen),
      has been widely used for treatment of cardiovascular diseases. Cardiac fibrosis
      is an important process in pathological cardiac remodeling and leads to heart
      failure. We investigated the effect of Danshensu on beta-adrenergic receptor
      (beta-AR)-mediated cardiac fibrosis and the involved signaling transduction.
      Danshensu inhibited cardiofibroblast proliferation and collagen I synthesis
      induced by isoproterenol (ISO), a selective beta-AR agonist. Phosphorylation of
      p38 mitogen-activated protein kinase (MAPK), which mediates ISO-induced cardiac
      fibrosis, was negatively regulated in this process. The negative regulation
      depended on the ISO inhibition of reactive oxygen species (ROS) production. Taken
      together, Danshensu may inhibit beta-AR-mediated cardiac fibrosis by negative
      regulation of ROS-p38 MAPK signaling. 

PMID- 24882407
TI  - Korean red ginseng extract exhibits neuroprotective effects through inhibition of
      apoptotic cell death.
AB  - Red ginseng has long been used as a traditional medicine in many East Asian
      countries including Korea. It is known to exhibit various pharmacological
      effects, including anti-oxidant, anti-cancer, anti-stress and anti-diabetes
      activities. To further explore its actions, the present study evaluated effects
      of Korean red ginseng (KRG) extract on neuronal injury induced by various types
      of insults using primary cultured rat cortical cells. KRG extract inhibited
      neuronal damage and generation of intracellular reactive oxygen species (ROS)
      induced by excitatory amino acids, such as glutamate and N-methyl-D-aspartate
      (NMDA), or by Abeta(25-35). To elucidate possible mechanism(s) by which KRG
      extract exerts neuroprotective action, its effects on apoptosis and apoptosis
      related signaling molecules in neurons were assessed. KRG extract markedly
      increased phosphorylation of Bad at Ser 112 and inhibited Bax expression and
      caspase 3 activity. It also inhibited DNA fragmentation induced by NMDA or
      Abeta(25-35). These results indicate that KRG extract protects cultured neurons
      from excitotoxicity and Abeta(25-35)-induced toxicity through inhibition of ROS
      generation and apoptotic cell death. In addition, KRG extract inhibited beta
      secretase activity, implying that it may reduce Abeta peptide formation. Taken
      together, these findings suggest that KRG extract may be beneficial for the
      prevention and/or treatment of neurodegenerative disorders including Alzheimer's
      disease. 

PMID- 24882409
TI  - X-ray crystallographic structure of RNase Po1 that exhibits anti-tumor activity.
AB  - RNase Po1 is a guanylic acid-specific ribonuclease member of the RNase T1 family
      from Pleurotus ostreatus. We previously reported that RNase Po1 inhibits the
      proliferation of human tumor cells, yet RNase T1 and other T1 family RNases are
      non-toxic. We determined the three-dimensional X-ray structure of RNase Po1 and
      compared it with that of RNase T1. The catalytic sites are conserved. However,
      there are three disulfide bonds, one more than in RNase T1. One of the additional
      disulfide bond is in the catalytic and binding site of RNase Po1, and makes RNase
      Po1 more stable than RNase T1. A comparison of the electrostatic potential of the
      molecular surfaces of these two proteins shows that RNase T1 is anionic whereas
      RNase Po1 is cationic, so RNase Po1 might bind to the plasma membrane
      electrostatically. We suggest that the structural stability and cationic
      character of RNase Po1 are critical to the anti-cancer properties of the protein.

PMID- 24882410
TI  - Sec61beta regulates barrier functions of tight junction through expression of
      claudin-4 in Madin-Darby canine kidney cells.
AB  - Sec61beta is the beta subunit of the Sec61 translocon and is responsible for
      expression and delivery of basolateral membrane proteins, including claudins,
      major constituents of tight junction (TJ). In the present study, the effect of
      Sec61beta overexpression on TJ barrier functions in Madin-Darby canine kidney
      (MDCK) cells were investigated by monitoring transepithelial electrical
      resistance (TER) and the expression and distribution of claudins. We adopted the
      time required by TER to reach 50% (T1/2) as a measure of TJ modulation rate.
      Sec61beta overexpression increased TER by post-transcriptionally upregulating
      claudin-4 expression and resulted in increased TER. Sec61beta overexpression
      increased TJ modulation rates (lower T1/2), in conjunction with enhanced delivery
      of claudin-4 from and to plasma membranes. Marked co-distribution and indirect
      association of claudin-4 with Sec61beta were observed, contributing to the
      enhanced delivery of claudin-4. Thus, Sec61beta may be a novel TJ modulation
      target, including barrier function and modulation rates for drug delivery
      systems. 

PMID- 24882411
TI  - Long-term high-soybean oil feeding alters regulation of body temperature in rats.
AB  - We investigated whether body temperature (BT) regulatory mechanisms are
      influenced by dietary fatty acids (FA). Male Wistar rats were fed a high-fat diet
      containing fish oil (HFD), soybean oil (HSD) or lard (HLD). At the 20-week
      intervention, the BT of the HSD and HLD groups were lower than that of the normal
      diet (ND) group in the light and dark periods. The intracerebroventricular
      injections of interleukin-1beta and bombesin in the HSD group induced greater
      hyperthermia and weaker hypothermia, respectively, than in the ND group. The HSD
      differentially affected BT under both physiological and pharmacological
      conditions. In the hypothalamus, the ratio of n-6/n-3 FAs was higher in the HSD
      group compared with the ND group. DNA microarrays revealed increased expression
      of thyroid-stimulating hormone beta-subunit, and decreased expression of several
      genes in the hypothalamus of the HSD group compared with the ND group. The HSD
      feeding increased several adipokine concentrations in the plasma. However, there
      were no adipokines or gene expressions that changed in only the HSD and HLD
      groups showing significant hypothermia under the physiological condition. These
      findings suggested that long-term HSD intake produces abnormal BT regulation. It
      is less likely that adipokines or proteins/peptides are involved in abnormal BT
      regulation under the physiological conditions after HSD feeding. 

PMID- 24882412
TI  - Collagen gel contraction assay using human bronchial smooth muscle cells and its
      application for evaluation of inhibitory effect of formoterol.
AB  - Collagen gel contraction assay is a method for evaluating contraction of cells
      embedded in collagen gel matrices through measuring the gel size. In the present
      study, we established a protocol for collagen gel contraction assay using human
      bronchial smooth muscle cells obtained commercially, and applied it for
      evaluation of inhibitory effect of formoterol on histamine-induced contraction.
      Human bronchial smooth muscle cells were embedded in collagen gel in wells of 24
      well plates, and gel contraction against histamine or acetylcholine was observed.
      Gel size was measured at an interval of 10 min for 60 min from the addition of a
      stimulant. Both acetylcholine and histamine caused gel contraction in a
      concentration-dependent manner and the contraction by histamine was apparently
      potent than that by acetylcholine. Formoterol at concentrations of 10(-10)-10(-7)
      M inhibited collagen gel contraction caused by histamine concentration
      dependently. Pre-treatment with fluticasone at a concentration of 10(-8) M
      apparently potentiated the inhibitory effect of formoterol at 10(-10) and 10(-8)
      M on collagen gel contraction by histamine. Prolonged pre-treatment with 10(-8) M
      formoterol abolished the inhibitory effect of 10(-8) M formoterol. Furthermore, 4
      h simultaneous pre-treatment with 10(-8) M formoterol and fluticasone partially
      but significantly recovered the inhibitory effect of 10(-8) M formoterol. Present
      results indicate that the collagen gel contraction assay using human bronchial
      smooth muscle cells is useful for evaluating the effects of bronchodilating
      drugs, and that fluticasone potentiates the inhibitory effect of formoterol on
      histamine-induced collagen gel contraction. 

PMID- 24882413
TI  - Papain-like protease (PLpro) inhibitory effects of cinnamic amides from Tribulus
      terrestris fruits.
AB  - Tribulus terrestris fruits are well known for their usage in pharmaceutical
      preparations and food supplements. The methanol extract of T. terrestris fruits
      showed potent inhibition against the papain-like protease (PLpro), an essential
      proteolylic enzyme for protection to pathogenic virus and bacteria. Subsequent
      bioactivity-guided fractionation of this extract led to six cinnamic amides (1-6)
      and ferulic acid (7). Compound 6 emerged as new compound possessing the very rare
      carbinolamide motif. These compounds (1-7) were evaluated for severe acute
      respiratory syndrome coronavirus (SARS-CoV) PLpro inhibitory activity to identify
      their potencies and kinetic behavior. Compounds (1-6) displayed significant
      inhibitory activity with IC50 values in the range 15.8-70.1 uM. The new cinnamic
      amide 6 was found to be most potent inhibitor with an IC50 of 15.8 uM. In kinetic
      studies, all inhibitors exhibited mixed type inhibition. Furthermore, the most
      active PLpro inhibitors (1-6) were proven to be present in the native fruits in
      high quantities by HPLC chromatogram and liquid chromatography with diode array
      detection and electrospray ionization mass spectrometry (LC-DAD-ESI/MS). 

PMID- 24882414
TI  - Antitumor activity of triterpenoid saponin-rich Adisia gigantifolia extract on
      human breast adenocarcinoma cells in vitro and in vivo.
AB  - The aim of this study was to explore whether the ethanolic extract of Ardisia
      gigantifolia rhizomes (AGB-5), a traditional herbal medicine from China, could
      affect the proliferation of human breast adenocarcinoma (MCF-7) cells in vitro
      and to explore the antitumor effects of AGB-5 in BALB/c mice engrafted with MCF-7
      cells. The results showed that AGB-5 markedly inhibited the proliferation of MCF
      7 cells with an IC50 value of 11.89+/-1.12 ug/mL, increased the S phase and
      decreased the G2/M phase without influence on G1 phase. MCF-7 cells treated with
      AGB-5 presented a dose-dependent increase of apoptosis compared with the control
      group. AGB-5 also significantly increased the activity of caspase-3 and -9 in a
      dose-dependent manner in MCF-7 cells. Furthermore, in an in vivo model, AGB-5
      reduced tumor volume, brought back the red blood cell (RBC) and white blood cell
      (WBC) count near to normal value, enhanced superoxide dismutase and catalase
      level of MCF-7 bearing mice. This is the first study to verify the antitumor
      activity of A. gigantifolia in vivo. The results suggest that AGB-5 may have
      potential beneficial effects against human breast adenocarcinoma. 

PMID- 24882415
TI  - Newly synthesized 'hidabeni' chalcone derivatives potently suppress LPS-induced
      NO production via inhibition of STAT1, but not NF-kappaB, JNK, and p38, pathways
      in microglia.
AB  - Chalcones are open-chain flavonoids that are biosynthesized in various plants.
      Some of them possess anti-inflammatory activity. We previously found that
      chalcone glycosides from Brassica rapa L. 'hidabeni' suppress lipopolysaccharide
      (LPS)-induced nitric oxide (NO) production in rat microglia highly aggressively
      proliferating immortalized (HAPI) cells. In this study, to explore chalcone
      derivatives with potent NO inhibitory activity, we synthesized ten compounds
      based on 'hidabeni' chalcone and examined their effects on LPS-triggered
      inducible NO synthase (iNOS) expression and NO production. Compounds C4 and C10
      potently inhibited NO production (IC50: 4.19, 2.88 uM, respectively). C4 and C10
      suppressed LPS-induced iNOS expression via the inhibition of the signal
      transduction and activator of transcription 1 (STAT1), but not nuclear factor
      kappa B (NF-kappaB), c-Jun N terminal kinase (JNK), and p38, pathways. C10, but
      not C4, inhibited activation of the MEK/extracellular signal-regulated kinase
      (ERK) pathway. C4 and C10 also suppressed LPS-induced expression of interferon
      regulatory factor 1 (IRF-1), which is an important transcription factor involved
      in iNOS expression. Our findings indicate that these chalcone derivatives are
      candidate compounds for preventing microglia-mediated neuroinflammation. 

PMID- 24882416
TI  - Inhalation administration of valerena-4,7(11)-diene from Nardostachys chinensis
      roots ameliorates restraint stress-induced changes in murine behavior and stress
      related factors.
AB  - Dried Nardostachys chinensis roots contain sesquiterpenoids that are widely used
      as herbal tranquilizers. We previously identified the highly sedative
      sesquiterpenoid valerena-4,7(11)-diene (VLD) from this plant. In the present
      study, we investigated stress reducing effects of VLD and the associated
      mechanisms of action. Application of 15-min restraint stresses induced excitatory
      behaviors in mice. Immobility times in the forced swim test and sleeping times in
      the pentobarbital sleep test were shortened in the stressed group by 47% and 43%,
      respectively, compared with the control group. Furthermore, restraint stress
      increased serum corticosterone levels by 75%, and cerebral serotonin (5-HT) and
      dopamine (DA) levels. Inhaled VLD (300 ug/cage) suppressed stress-induced
      excitatory behaviors and significantly reduced stress-induced blood
      corticosterone, cerebral 5-HT, and DA levels. These results suggest that VLD
      interacts with the hypothalamic-pituitary-adrenal axis and the sympathetic
      adrenomedullary system. These interactions appear to involve GABAergic and D2
      antagonist activities. Moreover, tests in anosmic and intravenously treated mice
      showed that the sedative effect of inhaled VLD was expressed via olfactory
      stimulation and pulmonary absorption. Although more studies are required to
      further elucidate the properties of this compound, our studies suggest that VLD
      may be an effective anti-stress aromatherapy for humans. 

PMID- 24882418
TI  - A meta-analysis of the association of PPARgamma rs1801282 polymorphism and NSAID
      usage with the risk of developing cancer.
AB  - Use of nonsteroidal anti-inflammatory drugs (NSAIDs) is correlated with a reduced
      risk of cancer through the reduction of inflammation, which is an important risk
      factor. Several studies have investigated polymorphisms in the peroxisome
      proliferator-activated receptor gamma (PPARgamma) gene and NSAID use in
      association with cancer risk. However, these studies yielded mixed results.
      Therefore, we performed a meta-analysis to evaluate the association of PPARgamma
      polymorphisms and NSAID usage with cancer risk. We conducted a comprehensive
      search of PubMed through May 2013. Odds ratios (ORs) with corresponding 95%
      confidence intervals (CIs) were calculated using the fixed-effect or random
      effect model. A comprehensive search of the database revealed 6 studies that
      fulfilled the inclusion criteria. NSAID use was significantly associated with
      decreased cancer risk regardless of PPARgamma rs1801282 genotypes. In a
      stratified analysis by cancer type, NSAID users who were minor allele carriers
      had significantly decreased colon cancer risk compared to non-NSAID users
      (OR=0.73, 95% CI=0.57-0.93), whereas NSAID users homozygous for the major allele
      had significantly decreased risk for cancers other than colon cancer compared to
      non-NSAID users (OR=0.79, 95% CI=0.69-0.91). Our results suggest that the
      association of PPARgamma rs1801282 polymorphism and NSAID use with the risk of
      cancer may differ according to cancer type. 

PMID- 24882417
TI  - Effect of short-term polyphenol treatment on endothelial dysfunction and
      thromboxane A2 levels in streptozotocin-induced diabetic mice.
AB  - Diabetes is characterized by the development of endothelial dysfunction, which
      affects both nitric oxide (NO)-mediated relaxation and endothelium-derived
      contracting factors, associated with vascular oxidative stress. There is a
      growing body of evidence suggesting that polyphenols have several beneficial
      effects, such as antioxidant and anti-inflammatory activities. This study
      investigated whether short-term treatment with polyphenols (chlorogenic acid
      (CA), morin (MO), resveratrol (RV)) can improve endothelial dysfunction related
      to diabetes. Aorta reactivity was determined in organ chambers, and we measured
      NO production and thromboxane B2 (TXB2; a metabolite of TXA2) from aortas in
      response to acetylcholine (ACh). Streptozotocin (STZ)-induced diabetic mice (16
      weeks) were injected with solvent (ethanol, 10% v/v; intraperitoneally (i.p.)),
      CA (0.03 mmol/kg/d), MO (0.03 mmol/kg/d), and RV (0.03 mmol/kg/d) for 5 d. The
      ACh-induced endothelium-dependent relaxation was markedly reduced in rings of STZ
      induced diabetic mice compared to controls. The treatment with polyphenols
      (significantly: MO, tendency: CA and RV) for only 5 d improved the NO components
      of relaxation, but did not normalize ACh-stimulated NO production. However,
      polyphenol treatment suppressed the ACh-stimulated level of TXB2 in aortas from
      STZ-induced diabetic mice. Thus, treatment with polyphenols caused basal NO
      production and a prompt improvement of the endothelial function in diabetic mice,
      and this may involve the normalization of TXA2 levels, not NO production, under
      ACh stimulation. 

PMID- 24882419
TI  - A novel transgenic mouse model carrying human Tribbles related protein 3 (TRB3)
      gene and its site specific phenotype.
AB  - Tribbles related protein 3 (TRB3) pseudokinase plays a crucial role in cell
      proliferation, migration and morphogenesis during development. In our recent
      study, an introduction of human TRB3 gene into mouse mammary tumor cells caused
      an increase of proliferation of tumor cells and their nuclear size. In the
      current study, to examine whether this gene causes de novo morphological changes
      in a specific organ site we have developed a novel variation of the transgenic
      mouse model that conditionally expresses human TRB3 (hTRB3) gene using Cre
      recombinase (Cre)/loxP recombination system. By injecting hTRB3 transgene
      construct into pronuclei of mouse embryo, we eventually obtained four hTRB3 mice.
      The gene expression was controlled by infection of adenovirus-expressing Cre via
      the tail vein of hTRB3 mouse. In Cre-mediated hTRB3 mouse, expression of the
      hTRB3 protein was detected in the cytoplasm of hepatocytes in the liver.
      Expression of this protein was also seen in lymphocytes in the spleen, glomerular
      endothelial cells, and epithelial cells of collecting duct of the kidney. In
      hepatocytes of the hTRB3 mouse, nuclear size was significantly greater than that
      of the wild type mouse, indicating that hTRB3 can play a role at least in part in
      hepatic morphogenesis. The present animal model may provide a system for
      evaluation of de novo morphological changes induced by a specific transgene in a
      specific organ site. 

PMID- 24882420
TI  - Significant decrease in plasma N-acetyl-seryl-aspartyl-lysyl-proline level in
      patients with end stage renal disease after kidney transplantation.
AB  - N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) is an endogenous peptide released
      from its precursor (thymosin-beta4) by prolyl oligopeptidase. AcSDKP is a natural
      inhibitor of pluripotent hematopoietic stem cell proliferation and is normally
      found in human plasma. AcSDKP has been shown to be a potent angiogenic factor and
      to suppress renal fibroblast proliferation. Impairment of renal function has been
      suggested to have a significant impact on plasma AcSDKP level. The aim of this
      study was to assess whether improvement of renal function after kidney
      transplantation has an impact on plasma AcSDKP-like immunoreactive substance (IS)
      level. Fourteen patients with end stage renal disease (ESRD) who were scheduled
      to undergo the first kidney allograft transplantation were enrolled. Plasma
      AcSDKP-IS levels were measured before and 3, 7, 10, 14, 21, 30, 60 and 90 d after
      kidney transplantation. Plasma AcSDKP-IS level decreased significantly from day 3
      after kidney transplantation compared to before kidney transplantation.
      Creatinine clearance increased significantly from day 7 after kidney
      transplantation. A significant negative correlation was observed between
      creatinine clearance and plasma AcSDKP-IS level from before transplantation to 90
      d after kidney transplantation. Stepwise multiple regression analysis identified
      creatinine clearance as the only significant independent factor associated with
      plasma AcSDKP-IS levels. These results suggest that recovery of kidney function
      after kidney transplantation may lead to a decrease in plasma AcSDKP level in
      patients with ESRD, and that plasma AcSDKP level may depend largely on renal
      function.

PMID- 24882421
TI  - Notices of retraction.

PMID- 24882422
TI  - The metabolic enhancer piracetam attenuates mitochondrion-specific endonuclease G
      translocation and oxidative DNA fragmentation.
AB  - This study was performed to investigate the involvement of mitochondrion-specific
      endonuclease G in piracetam (P)-induced protective mechanisms. Studies have shown
      the antiapoptotic effects of piracetam but the mechanism of action of piracetam
      is still an enigma. To assess the involvement of endonuclease G in piracetam
      induced protective effects, astrocyte glial cells were treated with
      lipopolysaccharide (LPS) and piracetam. LPS treatment caused significantly
      decreased viability, mitochondrial activity, oxidative stress, chromatin
      condensation, and DNA fragmentation, which were attenuated by piracetam
      cotreatment. Cotreatment of astrocytes with piracetam showed its significantly
      time-dependent absorption as observed with high-performance liquid
      chromatography. Astrocytes treated with piracetam alone showed enhanced
      mitochondrial membrane potential (MMP) in comparison to control astrocytes.
      However, in LPS-treated cells no significant alteration in MMP was observed in
      comparison to control cells. Protein and mRNA levels of the terminal executor of
      the caspase-mediated pathway, caspase-3, were not altered significantly in LPS or
      LPS + piracetam-treated astrocytes, whereas endonuclease G was significantly
      translocated to the nucleus in LPS-treated astrocytes. Piracetam cotreatment
      attenuated the LPS-induced endonuclease G translocation. In conclusion this study
      indicates that LPS treatment of astrocytes caused decreased viability, oxidative
      stress, mitochondrial dysfunction, chromatin condensation, DNA damage, and
      translocation of endonuclease G to the nucleus, which was inhibited by piracetam
      cotreatment, confirming that the mitochondrion-specific endonuclease G is one of
      the factors involved in piracetam-induced protective mechanisms. 

PMID- 24882424
TI  - Commentary on 'Physical activity monitoring in patients with peripheral arterial
      occlusive disease: validation of an activity monitor'.

PMID- 24882423
TI  - Evaluation of the accuracy of aorta scan BVI 9600 in screening for abdominal
      aortic aneurysm.
AB  - OBJECTIVES: Despite a decreasing incidence of abdominal aortic aneurysm (AAA),
      the cost-effectiveness of AAA ultrasound screening can be improved by reducing
      the screening costs and increasing the uptake rates. The BVI 9600 (BVI) is a
      promising tool for this purpose as it is inexpensive and can detect AAA without a
      trained operator. This study aims to investigate whether the BVI can be used to
      detect AAA for the purpose of a low-cost outreach screening approach. METHODS: A
      total of 142 subjects had their abdominal aortae measured by five sonographers
      using the BVI and a conventional ultrasound machine. The examination included
      four anterior-posterior measurements at four equally spaced scanning locations
      from the xiphisternum to the umbilicus. The measurements produced by each machine
      were compared using Bland-Altman plots, followed by an analysis of the AAA
      detection performance. RESULTS: The BVI measured the aortic diameter to within
      0.88-1.56 cm of the true diameter, exceeding the 0.5 cm "clinically acceptable
      difference" (CAD). Its accuracy was poorer when measuring the aneurysmal aortae
      (mean difference -0.56 cm, variability 1.72 cm) than normal aortae (mean
      difference 0.02 cm, variability 0.76 cm). Nine out of 52 aneurysms were not
      detected due to undersizing measurement and non-visualization of the aortae.
      CONCLUSIONS: At present, the BVI is not sufficiently accurate to detect AAA for
      screening purposes. A number of technical features require improvement.

PMID- 24882425
TI  - Meta-analysis of the association between N-methyl-d-aspartate receptor antibodies
      and schizophrenia, schizoaffective disorder, bipolar disorder, and major
      depressive disorder.
AB  - BACKGROUND: N-methyl-d-aspartate receptor (NMDAR) antibodies have been documented
      in the serum of individuals with primary psychiatric disorders from several
      independent cohorts, but these findings have not been systematically assessed in
      aggregate or in relation to methodological covariates. METHODS: We searched
      MEDLINE, EMBASE, and PsycINFO for studies in any language that provided data on
      NMDAR antibody seropositivity or absolute serum titers in schizophrenia or
      schizoaffective, bipolar, or major depressive disorders. We used a random effects
      model to pool estimates across studies. RESULTS: Nine studies met the eligibility
      criteria. Five studies (3387 participants) provided data on NMDAR antibody
      seropositivity in psychiatric versus control groups based on high-specificity
      seropositivity thresholds (cell-based assays [CBAs]: 1:320 dilution, 1:200
      dilution, visual score>1; enzyme-linked immunosorbent assay [ELISA]: 90(th)
      percentile of control titers). Meta-analysis showed significantly higher odds of
      NMDAR antibody seropositivity among those with schizophrenia or schizoaffective,
      bipolar, or major depressive disorders compared with healthy controls (odds ratio
      [OR], 3.10; 95% confidence interval [CI], 1.04-9.27; P=.043; I(2)=68%). Four
      studies (3194 participants) provided outcome data for these groups based on low
      specificity seropositivity thresholds (CBAs 1:10 dilution; ELISA: 75(th)
      percentile of control titers). Meta-analysis showed greater heterogeneity and no
      significant between-group difference (OR, 2.31; 95% CI, 0.55-9.73; P=.25;
      I(2)=90%). Seropositive participants in psychiatric groups had various
      combinations of IgG, IgM, and IgA class antibodies against NR1, NR1/NR2B, and
      NR2A/NR2B subunits. Subgroup analysis revealed significantly higher odds of
      seropositivity among all participants based on 1:10 versus 1:320 dilution
      seropositivity thresholds (OR, 4.56; 95% CI, 2.41-8.62; P<.001; I(2)=0%;
      studies=2, n=2920), but no apparent difference between first-episode and chronic
      schizophrenia or schizoaffective disorder (OR, 1.15; 95% CI, 0.19-7.24; P=.88,
      I(2)=43%, studies=2, n=1108). Average NR2A/NR2B antibody titers determined by
      ELISA were significantly higher among participants with first-episode
      schizophrenia (P<.0001) and acute mania (P<.01) compared with healthy controls.
      Levels decreased by 58% at 8weeks in first-episode schizophrenia, and by about
      13% at 4days in acute mania. CONCLUSIONS: Individuals with schizophrenia or
      schizoaffective, bipolar, or major depressive disorders are collectively about
      three times more likely to have elevated NMDAR antibody titers compared with
      healthy controls based on high-specificity, but not low-specificity,
      seropositivity thresholds, though considerable methodological and statistical
      heterogeneity exists. Evidence concerning the effect of disease state and time of
      serum acquisition is varied and consistent, respectively. Adequately powered
      longitudinal studies employing standardized assay methods and seropositivity
      threshold definitions, and quantifying NMDAR antibodies in both sera and
      cerebrospinal fluid are needed to further elucidate the clinical and
      pathophysiological implications of this association.

PMID- 24882426
TI  - Young women's attitudes towards, and experiences of, long-acting reversible
      contraceptives.
AB  - OBJECTIVES: To identify factors involved in women's decisions to choose
      particular contraceptive methods and more specifically, incentives and
      disincentives to use three long-acting reversible contraceptive (LARC) methods:
      injectables, implants, and intrauterine devices/systems (IUDs/IUSs). METHODS: A
      total of 502 women aged 18 to 30 completed a cross-sectional online
      questionnaire. RESULTS: The three most important factors in choosing a
      contraceptive method were: high efficacy at preventing pregnancy, protection
      against sexually transmitted infections, and non-interference with sexual
      intercourse. The most common incentives for LARC use were the high efficacy and
      long duration of action. Disincentives included the possibility of irregular
      bleeding and concerns about effects on fertility; fear of needles and pain was a
      particular disincentive for IUD/IUS use. Only 93 (18%) of the participants
      reported ever having used a LARC. CONCLUSIONS: Reported disincentives to LARC use
      (e.g., concern about effects on future fertility) indicated that many young women
      hold inaccurate beliefs about these methods. The relatively high proportions of
      women who held neutral attitudes about LARCs (21-40%, depending on the method)
      highlight the importance of education and contraceptive counselling to improve
      knowledge about the advantages of these methods.

PMID- 24882427
TI  - Mental health service utilization by Iraq and Afghanistan veterans after entry
      into PTSD specialty treatment.
AB  - OBJECTIVE: Use of care by Iraq and Afghanistan veterans was examined after entry
      into a U.S. Department of Veterans Affairs (VA) specialty outpatient program for
      treatment of posttraumatic stress disorder (PTSD). Those who had received mental
      health care before entry (continuing patients) were compared with those who had
      not (new patients). METHODS: Regression analyses compared veterans' retention in
      PTSD programs in the 180 days after program entry for new patients (N=172) and
      continuing patients (N=422). Two retention measures, total visits and completion
      of nine or more visits, were developed from VA administrative data. RESULTS: New
      patients completed fewer PTSD visits than did continuing patients (5.2+/-9.5
      versus 8.3+/-14.3; incidence risk ratio=.91, 95% confidence interval [CI]=.85
      .97) and were also less likely to complete nine or more visits (OR=.81, CI=.68
      .97). CONCLUSIONS: Contact with providers before entering PTSD specialty care may
      facilitate veterans' treatment engagement, suggesting the value of repeated
      attempts at engaging such veterans in treatment.

PMID- 24882428
TI  - Phylogenetic analysis of Maverick/Polinton giant transposons across organisms.
AB  - Polintons are a recently discovered group of large transposable elements (<40Kb
      in size) encoding up to 10 different proteins. The increasing number of genome
      sequencing projects has led to the discovery of these elements in genomes of
      protists, fungi, and animals, but not in plants. The RepBase database of
      eukaryotic repetitive elements currently contains consensus sequences and
      information of 70 Polinton elements from 28 organisms. Previous phylogenetic
      analyses have shown the relationship of Polintons to linear plasmids,
      bacteriophages, and retroviruses. However, a comprehensive phylogenetic analysis
      of all known Polintons has been lacking. We retrieved the Polinton consensus
      sequences from the most recent version of RepBase, and compiled amino acid
      sequences for the two most common Polinton-specific genes, the DNA polymerase-B
      and retroviral-like integrase. Open reading frame predictions and homology
      comparisons revealed partial or full sequences for 54 polymerases and 55 Polinton
      integrases. Multiple sequence alignments portrayed conservation in several
      functional motifs of these proteins. Phylogenetic analyses based on Bayesian
      inference using single- and combined-gene datasets revealed seven distinct
      lineages of Polintons that broadly follow the tree of life. Two of the seven
      lineages are found within the same species, indicating that ancient divergences
      have been retained to this day. 

PMID- 24882429
TI  - Can small hydrophobic gold nanoparticles inhibit beta2-microglobulin
      fibrillation?
AB  - Inorganic nanoparticles stabilized by a shell of organic ligands can enhance or
      suppress the natural propensity of proteins to form fibrils. Functionalization
      facilitates targeted delivery of the nanoparticles to various cell types,
      bioimaging, drug delivery and other therapeutic and diagnostic applications. In
      this study, we provide a computational model of the effect of a prototypical
      thiol-protected gold nanoparticle, Au25L18(-) (L = S(CH2)2Ph) on the beta2
      microglobulin natural fibrillation propensity. To reveal the molecular basis of
      the protein-nanoparticle association process, we performed various simulations at
      multiple levels (Classical Molecular Dynamics and Brownian Dynamics) that cover
      multiple length- and timescales. The results provide a model of the ensemble of
      structures constituting the protein-gold nanoparticle complexes, and insights
      into the driving forces for the binding of beta2-microglobulin to hydrophobic
      small size gold nanoparticles. We have found that the small nanoparticles can
      bind the protein to form persistent complexes. This binding of nanoparticles is
      able to block the active sites of domains from binding to another protein, thus
      leading to potential inhibition of the fibrillation activity. A comparison with
      the binding patches identified for the interaction of the protein with a known
      inhibitor of fibrillation, supports our conclusion.

PMID- 24882430
TI  - Mitral and aortic annular calcifications and cerebrovascular ischemic episodes in
      patients with coronary artery disease.
AB  - INTRODUCTION:  Atherosclerosis is a systemic pathological process involving the
      whole arterial bed. Valvular calcifications are associated with cardiovascular
      risk factors. Significant carotid stenosis accounts for approximately 20% of
      cerebrovascular ischemic episodes.  OBJECTIVES:  The aim of the study was to
      assess the relationship between mitral and aortic annular calcifications,
      increased carotid intima-media thickness (CIMT), and incidence of cerebrovascular
      ischemic episodes. PATIENTS AND METHODS:  A total of 127 patients with
      angiographically confirmed coronary artery disease (68 men and 59 women; aged 74
      (33-87) years) were divided into 4 groups: with aortic valve calcifications
      (AVCs), mitral annular calcifications (MACs), both aortic valve and mitral
      annular calcifications (AMVCs), and no valvular calcifications (no-VCs), based on
      the echocardiographic assessment of the mitral and aortic valves. CIMT and the
      presence of atherosclerotic plaques were evaluated by carotid ultrasonography. A
      history of cerebrovascular ischemic episodes was obtained.  RESULTS:  The
      combined prevalence of mitral or aortic valve calcifications in the study
      population was 59% (AVCs, 55%; MACs, 24%; and AMVCs, 21%). CIMT was significantly
      increased in the MAC and AMVC groups (P <0.05 for MACs; P <0.01 for AMVCs).
      Ischemic stroke was more common in the AVC group (P <0.05), while the MAC group
      had a higher incidence of carotid plaques (P <0.05), transient ischemic attacks
      (TIA; P <0.05), and strokes (P <0.05) as compared with the no-VC group. In
      multivariate analysis, only MACs remained independently associated with increased
      CIMT. CONCLUSIONS:  In patients with coronary artery disease, MACs are
      independently associated with increased CIMT but not with TIA or stroke. There is
      no relationship between the concomitant presence of mitral and aortic
      calcifications and carotid atherosclerosis.  

PMID- 24882431
TI  - Molecular genetics of Liddle's syndrome.
AB  - Liddle's syndrome, an autosomal dominant form of monogenic hypertension, is
      characterized by salt-sensitive hypertension with early penetrance, hypokalemia,
      metabolic alkalosis, suppression of plasma rennin activity and aldosterone
      secretion, and a clear-cut response to epithelial sodium channel (ENaC) blockers
      but not spironolactone therapy. Our understanding of ENaCs and Na(+) transport
      defects has expanded greatly over the past two decades and provides detailed
      insight into the molecular basis of Liddle's syndrome. In this review, we offer
      an overview of recent advances in understanding the molecular genetics of
      Liddle's syndrome, involving mutation analysis, molecular mechanisms and genetic
      testing. The ENaC in the distal nephron is composed of alpha, beta and gamma
      subunits that share similar structures. Mutations associated with Liddle's
      syndrome are positioned in either beta or gamma subunits and disturb or truncate
      a conserved proline-rich sequence (i.e., PY motif), leading to constitutive
      activation of the ENaC. Genetic testing has made it possible to make accurate
      diagnoses and develop tailored therapies for mutation carriers. 

PMID- 24882432
TI  - Chlamydia genomics: providing novel insights into chlamydial biology.
AB  - Chlamydiaceae are obligate intracellular pathogens that have successfully evolved
      to colonize a diverse range of hosts. There are currently 11 described species of
      Chlamydia, most of which have a significant impact on the health of humans or
      animals. Expanding chlamydial genome sequence information has revolutionized our
      understanding of chlamydial biology, including aspects of their unique lifecycle,
      host-pathogen interactions, and genetic differences between Chlamydia strains
      associated with different host and tissue tropisms. This review summarizes the
      major highlights of chlamydial genomics and reflects on the considerable impact
      these have had on understanding the biology of chlamydial pathogens and the
      changing nature of genomics tools in the 'post-genomics' era. 

PMID- 24882433
TI  - Medical communication: a core medical competence.

PMID- 24882435
TI  - Made-to-measure medicine: BRCA and gynaecological cancer.

PMID- 24882436
TI  - Janus nanoparticles as versatile phase-transfer reagents.
AB  - Janus nanoparticles were prepared by interfacial ligand-exchange reactions of
      hexanethiolate-protected gold (AuC6) nanoparticles with 3-mercapto-1,2
      propanediol (MPD) at the air|water interface. As nanoscale analogues to
      conventional amphiphilic molecules, the resulting Janus nanoparticles were found
      to form oil-in-water micelle-like or water-in-oil reverse micelle-like
      superparticulate structures depending on the solvent media. These unique
      characteristics were exploited for the effective transfer of diverse guest
      nanoparticles between organic and water phases. The transfer of hydrophobic
      nanoparticles from organic to water media or water-soluble nanoparticles to the
      organic phase was evidenced by transmission electron microscopy, dynamic light
      scattering, UV-vis, and photoluminescence measurements. In particular, line scans
      based on energy-dispersive X-ray analysis showed that the vesiclelike structures
      consisted of multiple layers of Janus nanoparticles which encapsulated the guest
      nanoparticles in the cores. The results highlight the unique effectiveness of
      using Janus nanoparticles in the formation of functional nanocomposites. 

PMID- 24882434
TI  - Olaparib maintenance therapy in patients with platinum-sensitive relapsed serous
      ovarian cancer: a preplanned retrospective analysis of outcomes by BRCA status in
      a randomised phase 2 trial.
AB  - BACKGROUND: Maintenance monotherapy with the PARP inhibitor olaparib
      significantly prolonged progression-free survival (PFS) versus placebo in
      patients with platinum-sensitive recurrent serous ovarian cancer. We aimed to
      explore the hypothesis that olaparib is most likely to benefit patients with a
      BRCA mutation. METHODS: We present data from the second interim analysis of
      overall survival and a retrospective, preplanned analysis of data by BRCA
      mutation status from our randomised, double-blind, phase 2 study that assessed
      maintenance treatment with olaparib 400 mg twice daily (capsules) versus placebo
      in patients with platinum-sensitive recurrent serous ovarian cancer who had
      received two or more platinum-based regimens and who had a partial or complete
      response to their most recent platinum-based regimen. Randomisation was by an
      interactive voice response system, stratified by time to progression on
      penultimate platinum-based regimen, response to the most recent platinum-based
      regimen before randomisation, and ethnic descent. The primary endpoint was PFS,
      analysed for the overall population and by BRCA status. This study is registered
      with ClinicalTrials.gov, number NCT00753545. FINDINGS: Between Aug 28, 2008, and
      Feb 9, 2010, 136 patients were assigned to olaparib and 129 to placebo. BRCA
      status was known for 131 (96%) patients in the olaparib group versus 123 (95%) in
      the placebo group, of whom 74 (56%) versus 62 (50%) had a deleterious or
      suspected deleterious germline or tumour BRCA mutation. Of patients with a BRCA
      mutation, median PFS was significantly longer in the olaparib group than in the
      placebo group (11.2 months [95% CI 8.3-not calculable] vs 4.3 months [3.0-5.4];
      HR 0.18 [0.10-0.31]; p<0.0001); similar findings were noted for patients with
      wild-type BRCA, although the difference between groups was lower (7.4 months [5.5
      10.3] vs 5.5 months [3.7-5.6]; HR 0.54 [0.34-0.85]; p=0.0075). At the second
      interim analysis of overall survival (58% maturity), overall survival did not
      significantly differ between the groups (HR 0.88 [95% CI 0.64-1.21]; p=0.44);
      similar findings were noted for patients with mutated BRCA (HR 0.73 [0.45-1.17];
      p=0.19) and wild-type BRCA (HR 0.99 [0.63-1.55]; p=0.96). The most common grade 3
      or worse adverse events in the olaparib group were fatigue (in ten [7%] patients
      in the olaparib group vs four [3%] in the placebo group) and anaemia (seven [5%]
      vs one [<1%]). Serious adverse events were reported in 25 (18%) patients who
      received olaparib and 11 (9%) who received placebo. Tolerability was similar in
      patients with mutated BRCA and the overall population. INTERPRETATION: These
      results support the hypothesis that patients with platinum-sensitive recurrent
      serous ovarian cancer with a BRCA mutation have the greatest likelihood of
      benefiting from olaparib treatment. FUNDING: AstraZeneca.

PMID- 24882438
TI  - The impact of indoor tanning legislation: newspaper coverage of the risks of
      indoor tanning before and after the California indoor tanning ban for minors.
AB  - On June 1, 2011, the California Senate passed a bill banning minors from indoor
      tanning. We aimed to determine whether the bill's passage was associated with
      longer-term media coverage regarding skin protection and the risks associated
      with indoor tanning. Articles from 31 English-language California newspapers
      between June 2010-May 2011 (PRE) and June 2011-May 2012 (POST) were searched
      using terms related to skin protection. Ninety articles were found for in-depth
      coding and analysis. There were more skin protection articles in the POST period
      than in the PRE period (57 vs 33; p < .05). In addition, there were more POST
      articles mentioning the risks of indoor tanning (33 vs 10; p < .001), and a POST
      article was more likely to mention the risks (58 vs 30%; p < .05). The higher
      number of POST articles mentioning the risks persisted throughout all quarters.
      Therefore, the California indoor tanning ban was associated with increased longer
      term news coverage of skin protection and the risks associated with indoor
      tanning. This finding has potential influence on the many states that are
      considering comparable legislation.

PMID- 24882437
TI  - Strategies for enrollment of African Americans into cancer genetic studies.
AB  - The enrollment of ethnically diverse populations in genetic and genomic research
      is vital to the parity of benefits resulting from research with biological
      specimens. Herein, we discuss strategies that may effectively improve the
      recruitment of African Americans into genetics studies. Specifically, we show
      that engaging physicians, genetic counselors, and community members is essential
      to enrolling participants into genetic studies. We demonstrate the impact of
      utilizing African American genetic counselors on study enrollment rates and
      implementing a two-page consent form that improved on a lengthy and inefficient
      consenting process. Lastly, we provided participants with the option of donating
      saliva instead of blood for study purposes. Descriptive statistics were used.
      Using the aforementioned strategies, recruitment goals for the Genetic Basis of
      Breast Cancer Subtype Study at Howard University (HU) were met. Our overall
      results yielded 182 participants in 18 months. Recruitment strategies that
      involve the engagement of physicians, genetic counselors, and community members
      may help researchers increase the enrollment of ethnically diverse and hard-to
      reach participants into genetic studies. 

PMID- 24882439
TI  - Oral cancer knowledge, behavior, and attitude among osteopathic medical students.
AB  - Approximately 21,000 osteopathic medical students were enrolled in the USA in
      2012-2013. These future physicians are being educated with an emphasis on a
      holistic or patient-centered approach, with a focus on preventive care.
      Considering the importance of preventive care and early diagnosis in the outcomes
      of oral malignancies, our goal in this study was to assess the knowledge,
      behavior, and attitude of osteopathic medical students in relation to oral
      cancer. To this end, 204 second-year (Y2) and 194 fourth-year (Y4) medical
      students were invited to participate in an electronic survey. Forty-one Y2 and 44
      Y4 students agreed to participate (20 and 22% response rate, respectively). The
      results showed that most Y2 and Y4 students were knowledgeable in certain areas
      (demographic features, important risk factors, and histologic feature), but
      deficient in others (clinical presentation, association of human papillomavirus
      (HPV) with oropharyngeal cancers, and screening recommendations). Head, neck, and
      oral examination habits were reported as being performed occasionally. Overall,
      students reported feeling uninformed about oral cancer and showed an interest in
      receiving further education on the subject. Our findings confirm that an overall
      improvement in oral cancer education in the medical curriculum is needed.
      Interprofessional collaboration between dental and medical schools may prove to
      be a valid approach to achieve this goal, which may possibly lead to increased
      detection of early oral cancerous lesions and, ultimately, improved mortality
      rates.

PMID- 24882440
TI  - Knowledge, experiences, and barriers to colorectal cancer screening: a survey of
      health care providers working in primary care settings.
AB  - Colorectal cancer (CRC) screening and early detection can effectively decrease
      the morbidity and mortality associated with this disease. Health care providers
      (HCPs) working in primary care settings as the first contact with the health care
      system can play a pivotal role in cancer prevention and screening for early
      detection. The purpose of this study was to explore the knowledge, experiences,
      and perceived barriers to CRC screening among HCPs working in primary care
      settings. A cross-sectional design and a self-administered questionnaire (SAQ)
      was used to collect data from 236 HCPs working in health centers in Jordan. The
      236 HCPs were nurses (45.8%), physicians (45.3%), and others (7.2%). A third of
      the HCPs (30%) knew the recommended age to begin CRC screening for patients with
      average risk. Overall physicians scored higher than nurses on questions assessing
      CRC screening knowledge. The majority of HCPs were not knowledgeable about CRC
      screening recommendations but believed that CRC is preventable (75.8%). The main
      perceived barriers to CRC screening were patient's fear of finding out that they
      have cancer and lack of awareness about CRC screening tests, shortage of trained
      HCPs to conduct invasive screening procedures, and lack of policy/protocol on CRC
      screening. HCPs working in primary care settings in Jordan do not have adequate
      knowledge about CRC screening. There is a need for tailored continuing
      educational programs and other interventions to improve HCPs' knowledge, as this
      can increase CRC screening in primary care settings and compliance with current
      screening guidelines.

PMID- 24882441
TI  - Perceptions of lung cancer and potential impacts on funding and patient care: a
      qualitative study.
AB  - The objective of this study was to explore health-care professionals', health
      administrators', and not-for-profit cancer organization representatives'
      perceptions of lung cancer-related stigma and nihilism and the perceived impacts
      on funding and patient care. This is a qualitative descriptive study using semi
      structured interviews, which was conducted in Ontario, Canada. Seventy-four
      individuals from medical oncology, radiation oncology, thoracic surgery,
      respirology, pathology, radiology, primary care, palliative care, nursing,
      pharmacy, social work, genetics, health administration, and not-for-profit cancer
      organizations participated in this study. Participants described lung cancer
      related stigma and nihilism and its negative impact on patients' psychological
      health, lung cancer funding, and patient care. The feeling of guilt and shame
      experienced by lung cancer patients as a result of the stigma associated with the
      disease was described. In terms of lung cancer funding, stigma was described as a
      reason lung cancer receives significantly less research funding compared to other
      cancers. In terms of patient care, lung cancer-related nihilism was credited with
      negatively impacting physician referral patterns with the belief that lung cancer
      patients were less likely to receive referrals for medical treatment. Health-care
      professionals, health administrators, and not-for-profit cancer organization
      representatives described lung cancer-related stigma and nihilism with far
      reaching consequences. Further work is needed to increase education and awareness
      about lung cancer to reduce the stigma and nihilism associated with the disease. 

PMID- 24882442
TI  - Acute effects of heavy metals on the expression of glutathione-related
      antioxidant genes in the marine ciliate Euplotes crassus.
AB  - Euplotes crassus, a single-celled eukaryote, is directly affected by
      environmental contaminants. Here, exponentially cultured E. crassus were exposed
      to cadmium, copper, lead, and zinc and then the reactive oxygen species (ROS) and
      total glutathione (GSH) levels were measured. Subsequently, the transcriptional
      modulation of glutathione peroxidase (GPx) and glutathione reductase (GR) were
      estimated by quantitative RT-PCR. After an 8-h exposure, significantly higher
      increases in the relative ROS and total GSH levels were observed in exposed
      group, compared to the controls. Real-time PCR data revealed that the expression
      levels of GPx and GR mRNA were sensitively modulated within 8h of exposure to all
      heavy metals. These findings suggest that these genes may be involved in cellular
      defense mechanisms by modulating their gene expression against heavy metal
      induced oxidative stress. Thus, they may be useful as potential molecular
      biomarkers to assess sediment environments for contaminants. 

PMID- 24882444
TI  - Comparative study of 17 beta-estradiol on endocrine disruption and
      biotransformation in fingerlings and juveniles of Japanese sea bass Lateolabrax
      japonicus.
AB  - Estrogenic contaminants in the aquatic environment are associated with endocrine
      disruption and feminization in fish. The effects of endocrine disrupting
      chemicals (EDCs) on fish have been well documented. However, very few studies
      have focused on 17 beta-estradiol (E2) and its effects on endocrine system and
      biotransformation in a single prolonged exposure. This study investigated changes
      in the levels of serotonin (5-hydroxytryptamine) and acetyl choline esterase
      (AchE) in brain, cortisol in plasma and Ethoxyresorufin-O-deethylase (EROD)
      activity in gill of two different size groups (fingerlings and juveniles) of
      Japanese sea bass (Lateolabrax japonicus) upon exposure to two sub-lethal
      concentrations (200 and 2000 ng L(-1)) of E2 for 30 d. The results indicate that
      cortisol level and EROD activity significantly increased in both groups, whereas
      serotonin level increased in juveniles and decreased in fingerlings due to E2
      exposure. The correlation analysis revealed that E2 significantly affected the
      endocrine and biotransformation systems in both age groups.

PMID- 24882443
TI  - Marine phytoplankton motility sensor integrated into a microfluidic chip for high
      throughput pollutant toxicity assessment.
AB  - A microfluidic chip was designed to assess the toxicity of pollutants in a high
      throughput way by using marine phytoplankton motility as a sensor signal. In this
      chip, multiple gradient generators (CGGs) with diffusible chambers enable large
      scale of dose-response bioassays to be performed in a simple way. Two mobile
      marine phytoplankton cells were confined on-chip and stimulated by 8
      concentrations (generated by CGG) of Hg, Pb, Cu and phenol singly, as well as Cu
      and phenol jointly. CASA system was used to characterize motility by motile
      percentage (%MOT), curvilinear velocity (VCL), average path velocity (VAP) and
      straight line velocity (VSL). In all cases, dose-dependent inhibitions of
      motility were observed. In the present system, only 2h was needed to predict
      EC50. Thus, the developed microfluidic chip device was proved to be useful as a
      rapid/simple and high-throughput test method in marine pollution toxicity
      assessment. 

PMID- 24882445
TI  - Benzo[a]pyrene modulates the biotransformation, DNA damage and cortisol level of
      red sea bream challenged with lipopolysaccharide.
AB  - In animals, biotransformation and the immune system interact with each other,
      however, knowledge of the toxic mechanism of benzo[a]pyrene (BaP) on these two
      systems is not well known. The present study investigated the toxic effects of
      BaP on the biotransformation system, cortisol level and DNA integrity of red sea
      bream (Pagrus major). The results showed that cortisol level was induced under
      the challenge of lipopolysaccharide (LPS). Short-term exposure (96 h) of BaP at
      environmental concentration significantly increased the cortisol level, hepatic
      EROD activity and CYP1A1 mRNA expression. When P. major was exposed to BaP for 14
      d followed by LPS challenge this increased the cortisol level, EROD activity and
      hepatic DNA damage except CYP1A1 mRNA expression. Combined with our previous
      data, which showed that BaP exposure can modulate the immunologic response in P.
      major challenged with LPS, a hypothetical adverse outcome pathway of BaP on fish
      was suggested.

PMID- 24882446
TI  - Cytotoxic cleistanthane and cassane diterpenoids from the entomogenous fungus
      Paraconiothyrium hawaiiense.
AB  - Hawaiinolides A-D (1-4), four new secondary metabolites including three
      cleistanthane (1, 3, and 4) and one cassane (2) type of diterpene lactones, were
      isolated from the crude extract of Paraconiothyrium hawaiiense, a fungus
      entomogenous to the Septobasidium-infected insect Diaspidiotus sp. The structures
      of 1-4 were elucidated by nuclear magnetic resonance experiments, and 1 and 3
      were further confirmed by X-ray crystallography. The absolute configuration of 1
      was assigned via single-crystal X-ray diffraction analysis using Cu Kalpha
      radiation, whereas that of 2-4 was deduced via the circular dichroism data.
      Compound 1 showed significant cytotoxicity against a small panel of five human
      tumor cell lines, A549, T24, HeLa, HCT116, and MCF-7. 

PMID- 24882447
TI  - A longitudinal study of neuropsychological functioning and academic achievement
      in children with and without signs of attention-deficit/hyperactivity disorder.
AB  - OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) in childhood is
      associated with poor academic functioning. Deficits in academic functioning have
      proven to be less responsive to intervention than behavioral deficits in this
      population, yet the causes of this academic underperformance are not well
      understood. The purpose of this study is to examine the relationship between ADHD
      and academic performance in elementary-aged children in a developmental context.
      To do this, we study important cognitive variables and academic achievement over
      a three-year timeframe. METHOD: Based on teacher ratings of ADHD, children were
      divided into a high symptom group (n = 17) and a low symptom group (n = 34). A
      thorough battery of cognitive and academic tests was administered at Time 1 and
      again 2 years later. Cognitive measures focused specifically on working memory
      and response inhibition. RESULTS: RESULTS indicate that children who have high
      levels of ADHD signs differ from their low-sign peers in academic achievement and
      in several cognitive domains. Differences in cognitive functioning show a
      developmental trend consistent with earlier developmental delays in response
      inhibition and later delays in working memory. Working memory appears to be
      particularly important in several academic domains. Importantly, in a
      longitudinal model, working memory was more predictive of math achievement for
      students demonstrating signs of ADHD than for those who did not. CONCLUSION: The
      relationship between these cognitive variables and academic functioning are
      explicated in the domains of reading, math, and problem solving.

PMID- 24882449
TI  - Who reports noticing and using calorie information posted on fast food restaurant
      menus?
AB  - OBJECTIVE: Identify consumer characteristics that predict seeing and using
      calorie information on fast food menu boards. METHODS: Two separate data
      collection methods were used in Philadelphia during June 2010, several weeks
      after calorie labeling legislation went into effect: (1) point-of-purchase survey
      and receipt collection conducted outside fast food restaurants (N = 669) and (2)
      a random digit dial telephone survey (N = 702). Logistic regressions were used to
      predict the odds of reporting seeing, and of reporting seeing and being
      influenced by posted calorie information. RESULTS: Approximately 35.1% of point
      of-purchase and 65.7% of telephone survey respondents reported seeing posted
      calorie information, 11.8% and 41.7%, respectively, reported that the labels
      influenced their purchasing decisions, and 8.4% and 17% reported they were
      influenced in a healthful direction. BMI, education, income, gender, consumer
      preferences, restaurant chain, and frequency of visiting fast food restaurants
      were associated with heterogeneity in the likelihood of reporting seeing and
      reporting seeing and using calorie labels. CONCLUSION: Demographic
      characteristics and consumer preferences are important determinants in the use of
      posted calorie information. Future work should consider the types of consumers
      this information is intended for, and how to effectively reach them.

PMID- 24882450
TI  - Sweetened blood sweetens behavior. Ego depletion, glucose, guilt, and prosocial
      behavior.
AB  - Although guilt feels bad to the individual, it is good for society because guilty
      feelings can prompt people to perform good deeds. Previous research shows that
      fatigue decreases guilty feelings and helpful behavior. This present research
      tests whether glucose restores guilty feelings and increases helpful behavior.
      Depleted participants watched a movie about butchering animals for their meat or
      skin and were told to express no emotions, whereas non-depleted participants
      watched the same movie, but could express their emotions. Afterwards they drank a
      glucose or placebo beverage. Having participants play a game in which another
      person was punished for their errors induced guilt. Finally, participants played
      a dictator game in which they could leave lottery tickets for the next
      participant. Depleted participants felt less guilty and helped less than non
      depleted participants, and those who consumed a placebo beverage felt less guilt
      and helped less than those who consumed a glucose beverage. 

PMID- 24882448
TI  - Disinhibited eating and weight-related insulin mismanagement among individuals
      with type 1 diabetes.
AB  - OBJECTIVE: Withholding insulin for weight control is a dangerous practice among
      individuals with type 1 diabetes; yet little is known about the factors
      associated with this behavior. Studies of nondiabetic individuals with weight
      concerns suggest that eating in a disinhibited manner (e.g., binge eating)
      predicts the use of maladaptive compensatory strategies (e.g., self-induced
      vomiting). The purpose of this study was to test whether individuals with type 1
      diabetes are less restrained in their eating when they think their blood glucose
      (BG) is low and whether this contributes to insulin omission for weight control
      purposes and subsequently higher hemoglobin A1c (HbA1c). METHODS: Two-hundred and
      seventy-six individuals with type 1 diabetes completed an online survey of eating
      behaviors, insulin dosing and most recent HbA1c. We used structural equation
      modeling to test the hypothesis that disinhibited eating when blood sugar is
      thought to be low predicts weight-related insulin mismanagement, and this, in
      turn, predicts higher HbA1c. RESULTS: The majority of participants endorsed some
      degree of disinhibition when they think their blood glucose is low (e.g., eating
      foods they do not typically allow) and corresponding negative affect (e.g.,
      guilt/shame). The frequency of disinhibited eating was positively associated with
      weight-related insulin mismanagement. Controlling for age, sex, education, and
      insulin pump use, the model explained 31.3% of the variance in weight-related
      insulin mismanagement and 16.8% of the variance in HbA1c. CONCLUSION: Addressing
      antecedents to disinhibited eating that are unique to type 1 diabetes (e.g.,
      perceived BG level) and associated guilt or shame may reduce weight-related
      insulin omission.

PMID- 24882451
TI  - Open-label study to evaluate the pharmacodynamics, clinical efficacy, and safety
      of meropenem for adult bacterial meningitis in Japan.
AB  - The aim of this study was to assess the efficacy, safety, and concentration of
      meropenem in cerebrospinal fluid when meropenem (2 g every 8 h) was administered
      to Japanese adult patients with bacterial meningitis. Five Japanese patients
      (mean age 60.6 years [range 35-71]) were enrolled. Infection with Streptococcus
      pneumoniae (three patients), Streptococcus salivarius (one patient), and
      Staphylococcus aureus (one patient) was confirmed by cerebrospinal fluid culture.
      Meropenem (2 g every 8 h) was administered to all five patients. Treatment
      duration ranged from 14 to 28 days (mean 22.6 days). All the patients were
      successfully treated. The concentration of meropenem in cerebrospinal fluid
      ranged from 0.27 to 6.40 MUg/ml up to 8.47 h and was over 1 MUg/ml 3 h after
      starting meropenem infusion. In each patient, the present study confirmed for the
      first time that the concentration of meropenem in cerebrospinal fluid exceeded
      the minimal inhibitory concentration for these pathogens. Eleven clinical and
      laboratory adverse events considered to be related to meropenem were observed in
      all patients, but no serious adverse event and no discontinuance of treatment due
      to adverse events occurred. Thus meropenem appeared to be a well-tolerated and
      effective agent for Japanese adult patients with bacterial meningitis. 2 g every
      8 h of meropenem was delivered to CSF and its concentration was exceed in MICs
      for the detected pathogens.

PMID- 24882452
TI  - Subdural hematoma--a rare complication of removal of osseointegrated auricular
      prosthesis retention system.
AB  - Periauricular osseointegrated prosthesis retention systems have been proven safe
      and effective in the management of microtia. Intracranial hemorrhage has been
      previously reported with implantation but is rare. We report a case of subdural
      hemorrhage following removal of an auricular prosthesis implant system. This case
      highlights the role of imaging, surgical technique, and neurosurgical support in
      prevention and management of intracranial hemorrhage associated with
      osseointegrated device removal. 

PMID- 24882453
TI  - Pediatric epistaxis: epidemiology, management & impact on quality of life.
AB  - OBJECTIVE: Epistaxis in the pediatric population is a common problem for both
      primary care physicians (PCPs) and otolaryngologists. Although a frequent reason
      for referral to ENT clinics, data is lacking regarding causes, effects on quality
      of life and common treatment modalities. METHODS: Prospective, clinical and
      questionnaire based study, with ethical approval. We identified 50 cases of
      pediatric epistaxis (<16 years old) over a 6-month period. A thorough clinical
      history was taken, first aid measures and management outcome was recorded. The
      impact of recurring epistaxis on parental quality of life was assessed using the
      Parental Stress Index Short Form (PSISF). RESULTS: Thirty-three males and 17
      females (2:1) were included. Mean age at presentation was 8.8 years. Initial
      management was inadequate, with only 30% of carers applying appropriate first aid
      measures. Quality of life was significantly affected in 10% of cases with primary
      parental concerns being fear of excessive blood loss and the stress of soiled
      bedclothes and night wear. Children were most affected by the negative impact on
      sporting activity. Otolaryngology consultation found the common causes to be
      iatrogenic trauma and rhinitis affecting "Littles" area. Of which 78% required
      silver nitrate cautery, and 22% just required reassurance and advice CONCLUSIONS:
      Recurrent minor nosebleeds in children can be troublesome and alarming for
      parents and children. We found the PSISF an easy and reliable method of assessing
      patient and parental stress in dealing with this problem. Raising awareness of
      simple management strategies among parents and PCPs could significantly reduce
      associated quality of life issues. Mucosal hydration, cautery and first aid
      advice are the fundamentals of management.

PMID- 24882454
TI  - Coexistence of Epstein-Barr virus and Parvovirus B19 in tonsillar tissue samples:
      quantitative measurement by real-time PCR.
AB  - OBJECTIVE: In this study, we aimed to investigate the presence and copy number of
      six different viruses in tonsillar tissue samples removed surgically because of
      chronic recurrent tonsillitis or chronic obstructive tonsillar hypertrophy.
      METHODS: In total, 56 tissue samples (tonsillar core) collected from 44 children
      and 12 adults were included in this study. The presence of viruses was
      investigated using a new TaqMan-based quantitative real-time PCR assay. RESULTS:
      Of the 56 tissue samples, 67.9% (38/56) were positive for at least one of the six
      viruses. Epstein-Barr virus was the most frequently detected virus, being found
      in 53.6% (30/56), followed by human Parvovirus B19 21.4% (12/56), human
      adenovirus 12.5% (7/56), human Cytomegalovirus 5.4% (3/56), BK polyomavirus 1.8%
      (1/56), and Herpes simplex virus 1.8% (1/56). Precancerous or cancerous changes
      were not detected in the tonsillar tissue samples by pathologic examination,
      whereas lymphoid hyperplasia was observed in 24 patients. In contrast to other
      viruses, B19 virus was present in high copy number in tonsillar tissues. The
      rates of EBV and B19 virus with high copy number (>500.000 copies/ml) were higher
      in children than in adults, and a positive relationship was also found between
      the presence of EBV and the presence of B19 virus with high copy number
      (P=0.037). CONCLUSIONS: It is previously reported that some viral agents are
      associated with different chronic tonsillar pathologies. In the present study,
      the presence of B19 virus in tonsillar core samples was investigated
      quantitatively for the first time, and our data suggests that EBV infections
      could be associated with B19 virus infections or could facilitate B19 virus
      replication. However, further detailed studies are needed to clarify this
      observation.

PMID- 24882455
TI  - Oral strength in subjects with a unilateral cleft lip and palate.
AB  - PURPOSE: Facial appearance and speech outcome may affect psychosocial functioning
      in girls and boys. Several studies reported dissatisfaction with facial
      appearance and more specifically the lip and mouth profile in children with cleft
      lip and palate (CLP). The purpose of this controlled study was to measure the
      tongue and lip strength and endurance in boys and girls with CLP. METHODS: Twenty
      five subjects (mean age: 10.6 years) with a unilateral CLP and a gender- and age-
      matched control group were selected. All subjects with an unilateral CLP
      consulted the same craniofacial team and had undergone an identical surgical
      procedure. Surgical procedure of the lip was performed using a modified Millard
      technique without primary nose correction at an average age of 5.5 months. The
      Iowa Oral Performance instrument was used to measure lip and tongue strength and
      tongue endurance. RESULTS: The results of the Iowa Oral Performance measurement
      showed no significant differences between the subjects with an unilateral cleft
      lip and palate and the age and gender matched control group without a cleft lip
      and palate. CONCLUSION: There is no significant differences regarding oral
      strength more specifically the lip and tongue strength and endurance between
      subjects with and without an unilateral cleft lip and palate. ENT specialists and
      speech pathologists must be aware of this aspect of the normal lip and tongue
      functions.

PMID- 24882456
TI  - Comparison between ABR with click and narrow band chirp stimuli in children.
AB  - OBJECTIVE: Click and chirp-evoked auditory brainstem responses (ABR) are applied
      for the estimation of hearing thresholds in children. The present study analyzes
      ABR thresholds across a large sample of children's ears obtained with both
      methods. The aim was to demonstrate the correlation between both methods using
      narrow band chirp and click stimuli. METHODS: Click and chirp evoked ABRs were
      measured in 253 children aged from 0 to 18 years to determine their individual
      auditory threshold. The delay-compensated stimuli were narrow band CE chirps with
      either 2000 Hz or 4000 Hz center frequencies. Measurements were performed
      consecutively during natural sleep, and under sedation or general anesthesia.
      Threshold estimation was performed for each measurement by two experienced
      audiologists. RESULTS: Pearson-correlation analysis revealed highly significant
      correlations (r=0.94) between click and chirp derived thresholds for both 2 kHz
      and 4 kHz chirps. No considerable differences were observed either between
      different age ranges or gender. Comparing the thresholds estimated using ABR with
      click stimuli and chirp stimuli, only 0.8-2% for the 2000 Hz NB-chirp and 0.4
      1.2% of the 4000 Hz NB-chirp measurements differed more than 15 dB for different
      degrees of hearing loss or normal hearing. CONCLUSION: The results suggest that
      either NB-chirp or click ABR is sufficient for threshold estimation. This holds
      for the chirp frequencies of 2000 Hz and 4000 Hz. The use of either click- or
      chirp-evoked ABR allows a reduction of recording time in young infants.
      Nevertheless, to cross-check the results of one of the methods, we recommend
      measurements with the other method as well.

PMID- 24882457
TI  - Response to the Letter to the Editor regarding "A long-term analysis of auricular
      position in pediatric patients who underwent post-auricular approaches".

PMID- 24882458
TI  - Inner ear anatomy in Waardenburg syndrome: radiological assessment and comparison
      with normative data.
AB  - OBJECTIVE: As patients with Waardenburg syndrome (WS) represent potential
      candidates for cochlear implantation, their inner ear anatomy is of high
      significance. There is an ongoing debate whether WS is related to any inner ear
      dysplasias. Our objective was to evaluate radiologically the inner ear anatomy in
      patients with WS and identify any temporal bone malformations. METHODS: A
      retrospective case review was carried out in a tertiary, referral center. The
      high resolution computed tomography (HRCT) scans of the temporal bone from 20
      patients (40 ears) with WS who were managed for deafness in a tertiary referral
      center from 1995 to 2012 were retrospectively examined. Measurements of 15
      different inner ear dimensions, involving the cochlea, the vestibule, the
      semicircular canals and the internal auditory meatus, as well as measurements of
      the vestibular aqueduct, were performed independently by two neuroradiologists.
      Finally, we compared the results from the WS group with a control group
      consisting of 50 normal hearing subjects (100 ears) and with previously reported
      normative values. RESULTS: Inner ear malformations were not found in any of the
      patients with WS. All measured inner ear dimensions were within the normative
      values compiled by our study group as well as by others. CONCLUSIONS: Inner ear
      malformations are not characteristic for all types of WS; however, certain rare
      subtypes might be related to inner ear deformities. Normative cochleovestibular
      dimensions that can help in assessing the temporal bone anatomy are provided.

PMID- 24882459
TI  - Recovery of vocal fold immobility following isolated patent ductus arteriosus
      ligation.
AB  - OBJECTIVE: Identify laryngoscopic and functional outcomes of infants with vocal
      fold immobility (VFI) following patent ductus arteriosus (PDA) ligation and
      identify predictors of recovery. METHODS: Retrospective review of patients with
      VFI following PDA ligation from 2001 to 2012 at a single institution. Inclusion
      criteria were: (1) PDA ligation as only cardiac surgical procedure; (2) left VFI
      documented by laryngoscopy; (3) minimum follow up 120 days, with at least 2
      laryngoscopies performed. Resolution of VFI was determined at follow-up
      laryngoscopy. Univariate logistic regression models were used to identify
      variables associated with VFI recovery. RESULTS: 66 subjects were included with
      median follow up of 3.0 (+/- 2.1) years. The mean gestational age was 24.5 +/-
      1.4 weeks, mean birth weight 673 +/- 167 g, and mean age at procedure was 18.6 +/
      14.3 days. Patients presented with respiratory symptoms (39%), dysphonia (78%)
      and dysphagia (55%). Resolution of VFI was observed in 2/66 (3%) patients.
      Recovery was documented at 20 days and 11 months respectively. Respiratory
      symptoms, dysphagia, and dysphonia persisted at last follow up in 11%, 47%, and
      20% of patients. CONCLUSIONS: VFI associated with ligation of the ductus
      arteriosus has a low rate of recovery. Clinical symptoms frequently persist, and
      as such regular follow-up by otolaryngologists to mitigate morbidity is
      indicated.

PMID- 24882460
TI  - Autoinflation for treatment of persistent otitis media with effusion in children:
      a cross-over study with a 12-month follow-up.
AB  - OBJECTIVES: The aims of the present study were to evaluate the efficacy of and
      compliance with a new device for autoinflation in the treatment of persistent
      otitis media with effusion (OME) in young children. METHODS: Forty-five children
      with persistent OME with a bilateral type B or C2 tympanogram for at least three
      months and history of subjective hearing loss, waiting for grommet surgery, were
      randomised to a treatment and a control group. Twenty-three children aged between
      three and eight years started as the treatment group with the new device for
      autoinflation. Another 22 children, aged between two and eight years were
      included as controls. After a period of four weeks, a cross-over was performed.
      Both groups underwent otomicroscopy, tympanometry and audiometry at inclusion and
      after one and two months for the evaluation of treatment efficiency. The primary
      outcome measurements were improvement in middle-ear pressure and hearing
      thresholds at eight weeks. Both groups were then followed up for another 10
      months. RESULTS: In the treatment group, the mean middle-ear pressure for both
      ears and the mean hearing thresholds for the best ear improved by 166 daPa
      (p<0.0001) and 6 dB (p<0.0001), respectively after four weeks, while in the
      control group, non-significant alterations were observed. After the cross-over of
      the control group to treatment, equivalent improvements in the mean middle-ear
      pressure and the mean hearing thresholds of 187 daPa (p<0.0001) and 7 dB
      (p<0.01), respectively were achieved also in this group. After treatment in both
      groups at eight weeks, four of 45 children were submitted to grommet surgery.
      During the long-term follow-up another five children were submitted to surgery
      due to recurrence of disease. All the children managed to perform the manoeuvre
      and no side-effects were detected. CONCLUSION: The device demonstrated efficiency
      in improving both middle-ear pressure and hearing thresholds in most children
      after four weeks of treatment. It might therefore be possible to consider this
      method of autoinflation in children with persistent OME during the watchful
      waiting period.

PMID- 24882462
TI  - Psychogenic pseudosyncope: diagnosis and management.
AB  - Psychogenic pseudosyncope (PPS) is the appearance of transient loss of
      consciousness (TLOC) in the absence of true loss of consciousness.
      Psychiatrically, most cases are classified as conversion disorder, which is
      hypothesized to represent the physical manifestation of internal stressors. The
      incidence of PPS is likely under-recognized and the disorder is under
      investigated in the unexplained syncope population, yet it can be diagnosed
      accurately with a focused history and confirmed with investigations including
      head-up tilt testing (HUTT), electroencephalogram (EEG; sometimes combined with
      video) or, in some centers, transcranial Doppler (TCD). Patients are more likely
      to be young females with an increased number of episodes over the past 6months.
      They frequently experience symptoms prior to their episodes including light
      headedness, shortness of breath and tingling. Conversion disorder is associated
      with symptomatic chronicity, increased psychiatric and physical impairment, and
      diminished quality of life. Understanding the epidemiology, biological
      underpinnings and approach to diagnosis of PPS is important to improve the
      recognition of this disorder so that patients may be managed appropriately. The
      general treatment approach involves limiting unnecessary interventions, providing
      the patient with needed structure, and encouraging functionality. While there are
      no treatment data available for patients with PPS, studies in related conversion
      disorder populations support the utility of psychotherapy. Psychotropic
      medications should be considered in patients with comorbid psychiatric disorders.

PMID- 24882463
TI  - Coordination between medical care providers and information technology resources
      in the management of patients with suicide attempts attending the emergency
      department.

PMID- 24882461
TI  - Innervation of amphibian reproductive system. Histological and ultrastructural
      studies.
AB  - In the present study we describe for the first time in anuran amphibians the
      histological and ultrastructural characteristics of innervation in the female
      reproductive organs. The observations in Rhinella arenarum revealed the presence
      of nerve fibers located predominantly in the ovarian hilium and in the oviduct
      wall. In both organs the nerves fibers are placed near blood vessels and smooth
      muscles fibers. In the present study the histological observations were confirmed
      using antibodies against peripherin and neurofilament 200 proteins.
      Ultrastructural analyses demonstrated that the innervation of the reproductive
      organs is constituted by unmyelinated nerve fibers surrounded by Schwann cells.
      Axon terminals contain a population of small, clear, translucent vesicles that
      coexist with a few dense cored vesicles. The ultrastructural characteristics
      together with the immunopositive reaction to tyrosine hydroxylase of the nerve
      fibers and the type of synaptic vesicles present in the axon terminal would
      indicate that the reproductive organs of R. arenarum females are innervated by
      the sympathetic division of the autonomic nervous system. 

PMID- 24882464
TI  - Sowing the seeds of health: is the era of food prescriptions coming?

PMID- 24882465
TI  - Myostatin inhibits proliferation and insulin-stimulated glucose uptake in mouse
      liver cells.
AB  - Although myostatin functions primarily as a negative regulator of skeletal muscle
      growth and development, accumulating biological and epidemiological evidence
      indicates an important contributing role in liver disease. In this study, we
      demonstrate that myostatin suppresses the proliferation of mouse Hepa-1c1c7
      murine-derived liver cells (50%; p < 0.001) in part by reducing the expression of
      the cyclins and cyclin-dependent kinases that elicit G1-S phase transition of the
      cell cycle (p < 0.001). Furthermore, real-time PCR-based quantification of the
      long noncoding RNA metastasis associated lung adenocarcinoma transcript 1
      (Malat1), recently identified as a myostatin-responsive transcript in skeletal
      muscle, revealed a significant downregulation (25% and 50%, respectively; p <
      0.05) in the livers of myostatin-treated mice and liver cells. The importance of
      Malat1 in liver cell proliferation was confirmed via arrested liver cell
      proliferation (p < 0.05) in response to partial Malat1 siRNA-mediated knockdown.
      Myostatin also significantly blunted insulin-stimulated glucose uptake and Akt
      phosphorylation in liver cells while increasing the phosphorylation of
      myristoylated alanine-rich C-kinase substrate (MARCKS), a protein that is
      essential for cancer cell proliferation and insulin-stimulated glucose transport.
      Together, these findings reveal a plausible mechanism by which circulating
      myostatin contributes to the diminished regenerative capacity of the liver and
      diseases characterized by liver insulin resistance. 

PMID- 24882468
TI  - Evaluation of back contact in spray deposited SnS thin film solar cells by
      impedance analysis.
AB  - The role of back metal (M) contact in sprayed SnS thin film solar cells with a
      configuration Glass/F:SnO2/In2S3/SnS/M (M = Graphite, Cu, Mo, and Ni) was
      analyzed and discussed in the present study. Impedance spectroscopy was employed
      by incorporating constant phase elements (CPE) in the equivalent circuit to
      investigate the degree of inhomogeneity associated with the heterojunction and
      M/SnS interfaces. A best fit to Nyquist plot revealed a CPE exponent close to
      unity for thermally evaporated Cu, making it an ideal back contact. The Bode
      phase plot also exhibited a higher degree of disorders associated with other
      M/SnS interfaces. The evaluation scheme is useful for other emerging solar cells
      developed from low cost processing schemes like spray deposition, spin coating,
      slurry casting, electrodeposition, etc. 

PMID- 24882467
TI  - Post-operative complications following adenotonsillectomy in children with severe
      sleep apnea-hypopnea syndrome. Do they need to be admitted to an intensive care
      unit?
AB  - INTRODUCTION AND OBJECTIVES: In recent years, with the rise of sleep-disordered
      breathing, we have been seeing more articles related to post-operative
      complications after adenotonsillectomy in children with sleep apnea-hypopnea
      syndrome (OSAS), especially in those with severe sleep apnea. The objective of
      this study was to evaluate post-operative complications in children with severe
      OSAS compared to children who had adenotonsillectomy for a different reason, and
      establish whether they needed admission to an intensive care unit or not.
      METHODS: All children undergoing adenotonsillectomy in our hospital in the last 5
      years were initially included in this study. Complications were analysed with a
      retrospective review. RESULTS: Two hundred and twenty nine children admitted for
      adenotonsillectomy were finally included. In the whole group, complications
      occurred in 3.5% of children, 2.2% corresponding to respiratory complications.
      Children with sleep apnea (3.23% vs 1.47%, P=.39) or severe sleep apnea (3.77% vs
      1.70%, P=.32) presented a higher incidence of respiratory complications, which
      was not statistically significant and was far below those published by other
      authors. All respiratory complications took place in the immediate post-operative
      period (operating theatre or anaesthesia recovery), with none in the paediatric
      ward. CONCLUSIONS: In our population, children who undergo adenotonsillectomy,
      without any other comorbidities, malformation syndrome or neuromuscular disease,
      are more than 2 years old and have an immediate postoperative period without
      incidence, do not need to be systematically admitted to an intensive care unit,
      even if they present with severe OSAS.

PMID- 24882466
TI  - Disruption of Pten speeds onset and increases severity of spontaneous colitis in
      Il10(-/-) mice.
AB  - BACKGROUND & AIMS: Early-onset ulcerative colitis, which is considered severe
      colonic inflammation that develops in infants and young children, can be caused
      by alterations in interleukin (IL)-10 signaling, although other factors are
      involved in its pathogenesis. We investigated whether loss of phosphatase and
      tensin homologue (PTEN), which regulates many important cell functions such as
      cell proliferation, cell survival, and Toll-like receptor (TLR) signaling
      pathways, contributes to the development of colitis in Il10(-/-) mice. METHODS:
      We generated Il10(-/-) mice (in C57BL/6 and C3H/HeJBir background strains) with
      disruption of Pten in the intestinal epithelium (Ints(DeltaPten/DeltaPten);Il10(
      /-) mice) and Ints(DeltaCont);Il10(-/-) (control) mice. Colon tissues were
      collected and histological, transmission electron microscopy, and gene expression
      analysis were performed. Fecal microbiota samples were analyzed by sequencing of
      16S ribosomal RNA genes. We disrupted Tlr4 in Ints(DeltaPten/DeltaPten);Il10(-/-)
      mice. Lipopolysaccharide signaling via TLR4 was blocked by treating mice with
      polymyxin B. RESULTS: Il10(-/-) mice developed colitis when they were 6 to 7
      months old, whereas Ints(DeltaPten/DeltaPten);Il10(-/-) mice developed severe
      colitis and colon tumors by the time they were 36 days old. Within 3 months of
      birth, 80% of Ints(DeltaPten/DeltaPten);Il10(-/-) mice developed severe colitis
      and colonic malignancy, whereas none of the Ints(DeltaCont);Il10(-/-) mice had
      these phenotypes. Ints(DeltaPten/DeltaPten);Il10(-/-) mice had alterations in
      fecal microbiota compared with controls, such as increased proportions of
      Bacteroides species, which are gram negative. Disruption of Tlr4 or treating
      Ints(DeltaPten/DeltaPten);Il10(-/-) mice with polymyxin B delayed the development
      of colitis and reduced disease severity. CONCLUSIONS: Disruption of Pten in the
      intestinal epithelium of Il10(-/-) mice speeds the onset and increases the
      severity of colitis. Fecal microbiota from Ints(DeltaPten/DeltaPten);Il10(-/-)
      mice have increased proportions of Bacteroides species. Development of colitis is
      delayed and reduced by blocking TLR4 signaling. Ints(DeltaPten/DeltaPten);Il10(-/
      ) mice may be studied as a model for early-onset ulcerative colitis and used to
      identify new therapeutic targets.

PMID- 24882471
TI  - Budget cuts risk halting Australia's progress in preventing chronic disease.

PMID- 24882472
TI  - Acute respiratory infections among Indigenous children.

PMID- 24882473
TI  - Uptake of medicines and prescribing patterns in the palliative care schedule of
      the Pharmaceutical Benefits Scheme.

PMID- 24882476
TI  - Health reform and activity-based funding.

PMID- 24882477
TI  - Is it time for Medi-change?

PMID- 24882478
TI  - Should the legal age for alcohol purchase be raised to 21?

PMID- 24882479
TI  - The withdrawal of the Liverpool Care Pathway in the United Kingdom: what are the
      implications for Australia?

PMID- 24882480
TI  - Melbourne takes the world to heart - and vice versa.

PMID- 24882481
TI  - (Ir)responsible drinking campaigns.

PMID- 24882482
TI  - Liaise with pathologists to refine understanding of the prostate-specific antigen
      test.

PMID- 24882483
TI  - Difficult but necessary conversations - the case for advance care planning.

PMID- 24882484
TI  - Liaise with pathologists to refine understanding of the prostate-specific antigen
      test. Reply.

PMID- 24882485
TI  - The hidden issues of anticipatory medications in community palliative care.

PMID- 24882486
TI  - Removing the interview for medical school selection is associated with gender
      bias among enrolled students.

PMID- 24882487
TI  - Rural clinical school outcomes: what is success and how long do we wait for it?

PMID- 24882488
TI  - Rural, urban: the real world for medical education.

PMID- 24882489
TI  - Prostate cancer survivorship: a review of erectile dysfunction and penile
      rehabilitation after prostate cancer therapy.
AB  - Prostate cancer diagnosis and treatment adversely affect quality of life for most
      men. The true incidence of erectile dysfunction (ED) after prostate cancer
      therapy is unknown, and the rates of ED in radical prostatectomy (RP) and
      radiation groups are similar, although the onset of ED is often later in patients
      treated with radiation therapy. Proposed pathophysiological mechanisms of ED
      include neurovascular injury, local inflammatory changes, damage to nearby
      supporting structures, cavernosal smooth muscle hypoxia with ensuing smooth
      muscle apoptosis and fibrosis, and corporal veno-occlusive dysfunction causing
      venous leakage. Penile rehabilitation aims to help men regain the ability to
      achieve erections sufficient for satisfactory sexual intercourse during
      rehabilitation from prostate cancer treatment, and ultimately to return to
      pretreatment erectile function. While there is no consensus on the ideal
      rehabilitation regimen, many sexual health experts agree that treatment should
      start as soon as possible to protect and/or prevent corporal endothelial and
      smooth muscle damage. Current management strategies for erectile function
      rehabilitation predominantly relate to patients who have had RP.
      Phosphodiesterase type 5 inhibitors, intracavernosal injection of vasoactive
      agents and vacuum erection devices are options which can be used in a
      rehabilitation program. Penile implants should be considered if patients do not
      respond to medical therapies. To facilitate informed decision making, patients
      should be presented with all treatment options, and told that rehabilitation and
      treatment for ED as early as possible after prostate cancer therapy will result
      in faster and better recovery of erectile function and preserve sexual
      continuity. 

PMID- 24882490
TI  - Geographic variation in prostate cancer survival in New South Wales.
AB  - OBJECTIVES: To determine whether the previously reported urban-rural differential
      in prostate cancer survival remains after adjusting for demographic and clinical
      factors, and to investigate temporal trends in this differential. DESIGN, SETTING
      AND PARTICIPANTS: Retrospective population-based survival analysis of 68 686 men
      diagnosed with prostate cancer from January 1982 to December 2007 in New South
      Wales. MAIN OUTCOME MEASURES: Survival rate and relative excess risk (RER) of
      death over 10 years of follow-up in relation to geographic remoteness after
      adjusting for other prognostic factors. RESULTS: Overall, 10-year survival
      increased during the study period, increasing from 57.5% in 1992-1996 and 75.7%
      in 1997-2001 to 83.7% in 2002-2007. The increasing trends were also observed
      across categories of geographic remoteness and socioeconomic status. Urban-rural
      differentials were significant (P < 0.001) after adjusting for five important
      prognostic factors, with men living outside major cities having higher risk of
      death from prostate cancer (RER, 1.18 and 1.32 for inner regional and rural
      areas, respectively). Socioeconomic status was also a significant factor (P <
      0.001) for prostate cancer mortality, with the risk of dying being 34% to 40%
      higher for men living in socioeconomically disadvantaged areas than those living
      in least disadvantaged areas. There was no evidence that this inequality is
      reducing over time, particularly for men living in inner regional areas.
      CONCLUSIONS: Despite the increasing awareness of urban-rural differentials in
      cancer outcomes, little progress has been made. Appropriately detailed data,
      including details of tumour characteristics, treatment and comorbid conditions,
      to help understand why these inequalities exist are required urgently so
      interventions and policy changes can be guided by appropriate evidence.

PMID- 24882491
TI  - Paediatric hospitalisations for lower respiratory tract infections in Mount Isa.
AB  - OBJECTIVE: To compare the rates of acute lower respiratory tract infection (ALRI)
      among children in north-west Queensland, according to age, sex and Indigenous
      status. DESIGN, SETTING AND PATIENTS: Retrospective chart review of
      hospitalisations at Mt Isa Base Hospital, Queensland, from 1 January 2007 to 31
      December 2011 among children < 15 years of age. MAIN OUTCOME MEASURES: Rates of
      admission for bronchiolitis, pneumonia and bronchiectasis, calculated using
      population data from the Australian Bureau of Statistics. RESULTS: There were 356
      admissions for ALRI, involving 276 children. Of the 162 children aged < 12 months
      old, 125 (77.2%) were Indigenous. Hospitalisations increased over the study
      period, and rates were significantly higher among Indigenous children compared
      with non-indigenous children (24.1 v 4.5 per 1000 population per year). There
      were 195 admissions of 164 children with pneumonia, 126 (76.8%) of whom were
      Indigenous. Annual rates for Indigenous children were higher than for non
      Indigenous children (13.7 v 2.3 per 1000 population). Multiple admissions were
      common. One-third presented with gastrointestinal symptoms and signs.
      Pneumococcal disease persisted despite vaccination. There were 160
      hospitalisations for bronchiolitis; 114 occasions (71.3%) involved Indigenous
      children. Seven children had bronchiectasis; all were Indigenous. CONCLUSION:
      Rates of ALRI in Mt Isa are comparable to those in the Northern Territory, which
      is reported to have rates of pneumonia among the highest in the world for
      children < 12 months of age. Multiple admissions are common, suggesting an even
      higher rate of bronchiectasis. Pneumonia may present as gastrointestinal disease,
      and invasive pneumococcal infection must be suspected despite vaccination.

PMID- 24882493
TI  - Acute allergic reaction after intravenous saline injection: an unusual
      presentation of chlorhexidine allergy.

PMID- 24882492
TI  - High chlamydia positivity rates in Indigenous people attending Australian sexual
      health services.
AB  - OBJECTIVE: To assess the clinical epidemiology of chlamydia among Aboriginal and
      Torres Strait Islander (Indigenous) people attending sexual health services
      around Australia. DESIGN: Retrospective analysis of routine demographic,
      behavioural and clinical data, between 1 January 2006 and 31 December 2011.
      SETTING: 18 sexual health services in major cities and regional centres in five
      jurisdictions. MAIN OUTCOME MEASURES: Attendance, chlamydia testing and
      positivity rates in patients visiting for the first time, and factors associated
      with chlamydia positivity. RESULTS: Of 168 729 new patients, 7103 (4.2%)
      identified as Indigenous, of whom 74.3% were tested for chlamydia. Chlamydia
      positivity was 17.0% in Indigenous women (23.3% in 15-19-year-olds and 18.9% in
      20-24-year-olds) and 17.3% in Indigenous men (20.2% in 15-19-year-olds and 24.2%
      in 20-24-year-olds). There was an increasing trend in chlamydia positivity in
      Indigenous women from 2006 to 2011 (P for trend = 0.001), but not in Indigenous
      men. In Indigenous women, factors independently associated with positivity were:
      younger age, being heterosexual, living in Queensland and attending the service
      in 2010. In Indigenous men, independent factors associated with chlamydia
      positivity were younger age, being heterosexual, having sex only in Australia and
      living in a regional area. CONCLUSION: The high and increasing chlamydia
      positivity rates highlight the need for enhanced prevention and screening
      programs for Indigenous people.

PMID- 24882494
TI  - What would Repin do? The daily grind was not restricted to coffee.

PMID- 24882495
TI  - Tuck shop is target: school bans "cigarettes" after parents' complaints. 1983.

PMID- 24882496
TI  - Enhanced immune responses in pigs by DNA vaccine coexpressing GP3 and GP5 of
      European type porcine reproductive and respiratory syndrome virus.
AB  - The European (EU) type of porcine reproductive and respiratory syndrome virus
      (PRRSV) has recently emerged in China. In this study, three recombinant DNA
      vaccines, pVAX1-EU-ORF3-ORF5 (coexpressing EU type PRRSV GP3 and GP5), pVAX1-EU
      ORF3 and pVAX1-EU-ORF5, were constructed and evaluated for their abilities to
      induce humoral and cellular responses as well as to protect piglets against
      homologous virus challenge. All piglets were given booster vaccinations at 21
      days after the initial inoculation and then challenged 14 days later. Pigs
      inoculated with pVAX1-EU-ORF3-ORF5 developed significantly higher (P<0.05) PRRSV
      specific antibody responses, neutralizing antibodies and levels of IL-4 and IL-10
      than those given pVAX1-EU-ORF3, pVAX1-EU-ORF5 or pVAX1. Moreover, pigs immunized
      with pVAX1-EU-ORF3-ORF5 had markedly increased levels of IFN-gamma and IL-2 in
      serum and T-lymphocytes (CD3(+)CD4(+) and CD3(+)CD8(+) T cells) in peripheral
      blood. Thus, EU-type PRRSV GP3 and GP5 proteins demonstrated good immunogenicity
      and reactogenicity and could induce cellular immunity in pigs. Following
      challenge with the Lelystad virus (LV) strain, piglets inoculated with pVAX1-EU
      ORF3-ORF5 showed viremia and virus load distributed in organ tissues that were
      significantly lower (P<0.05) than those in the pVAX1-EU-ORF3 group and control
      group, and slightly lower than those in the pVAX1-EU-ORF5 group (P>0.05). As GP3
      could enhance humoral- and cell-mediated immune responses to GP5, the results of
      this study suggested that these two proteins delivered by a vaccine can
      synergistically induce immunity against PRRSV. 

PMID- 24882497
TI  - Validation of a sensitive PCR assay for the detection of Chelonid fibropapilloma
      associated herpesvirus in latent turtle infections.
AB  - The Chelonid fibropapilloma-associated herpesvirus (CFPHV) is hypothesized to be
      the causative agent of fibropapillomatosis, a neoplastic disease in sea turtles,
      given its consistent detection by PCR in fibropapilloma tumours. CFPHV has also
      been detected recently by PCR in tissue samples from clinically healthy (non
      exhibiting fibropapilloma tumours) turtles, thus representing presumably latent
      infections of the pathogen. Given that template copy numbers of viruses in latent
      infections can be very low, extremely sensitive PCR assays are needed to optimize
      detection efficiency. In this study, efficiency of several PCR assays designed
      for CFPHV detection is explored and compared to a method published previously.
      The results show that adoption of a triplet set of singleplex PCR assays
      outperforms other methods, with an approximately 3-fold increase in detection
      success in comparison to the standard assay. Thus, a new assay for the detection
      of CFPHV DNA markers is presented, and adoption of its methodology is recommended
      in future CFPHV screens among sea turtles. 

PMID- 24882498
TI  - Public health research: Institutional review board review or no institutional
      review board review?

PMID- 24882499
TI  - Olfactory event-related potentials in infants.
AB  - OBJECTIVES: To evaluate olfactory event-related potentials (OERPs) as an
      objective measurement of olfactory function in infants. STUDY DESIGN: OERPs to
      phenylethyl alcohol were measured in 13 infants, between 23 and 41 days of age.
      The odor was delivered with a computer-controlled olfactometer. Recording
      electrodes were applied using the 10-20 system. Data from electrodes Fz, Cz, Pz,
      C3, and C4 were analyzed by MatLab's Letswave toolbox (Andre Mouraux, Brussels,
      Belgium) using the canonical time-domain averaging as well as the time-frequency
      analyzing method. RESULTS: Ten of 13 infants finished the recording session. We
      observed OERPs in 7 of these 10 infants. Recordings were best in electrodes Fz
      and Cz. The N1 peak was visible at 328 ms followed by P2 at 505 ms. In addition,
      the time-frequency analysis had an increase in low frequencies (4-7 Hz) around
      550 ms after odor presentation. CONCLUSIONS: We were able to record OERPs in
      infants. The time-domain averaging as well as the time-frequency analysis was of
      value for data analysis.

PMID- 24882500
TI  - Identification of the metabolites of myricitrin produced by human intestinal
      bacteria in vitro using ultra-performance liquid chromatography/quadrupole time
      of-flight mass spectrometry.
AB  - OBJECTIVE: To investigate the metabolic routes and metabolites of myricitrin, an
      important active ingredient of traditional herbal medicine, yielded by the
      isolated human intestinal bacteria, which have not been reported previously.
      METHODS: Fresh human fecal samples were collected from a healthy female volunteer
      and about 100 different bacterial colonies were isolated. Ultra-performance
      liquid chromatography/quadrupole time-of-flight mass spectrometry technique
      combined with MetabolynxTM software was used for analysis of the metabolic
      profile of myricitrin by the isolated human intestinal bacteria. RESULTS: One
      hundred different bacterial colonies, which developed on plates, were picked up,
      and four of them were further identified by using the technique of 16S rRNA gene
      sequencing due to their relatively strong metabolic capacity toward myricitrin.
      Most of them belong to Escherichia. Parent compound and three metabolites
      (quercetin-3-O-rhamnoside, myricetin and quercetin) were detected in the isolated
      bacterial samples compared with blank samples. The metabolic pathways of
      myricitrin included deglycosylation and dehydroxylation. CONCLUSIONS: These
      metabolites suggested that myricitrin was first dehydroxylated to quercetin-3-O
      rhamnoside and subsequently deglycosylated to quercetin. Additionally, myricitrin
      could also be deglycosylated to the aglycon myricetin. Moreover, those
      metabolites might influence the biological effect of myricitrin in vivo, which
      led to affect the clinical effects of the medicinal plants and traditional herb
      medicines.

PMID- 24882501
TI  - Clinical evidence of field cancerization in patients with oral cavity cancer in a
      betel quid chewing area.
AB  - OBJECTIVES: We sought to investigate whether there is evidence of field
      cancerization in patients with oral cavity squamous cell carcinoma (OSCC)
      enrolled in a betel quid chewing area. We also assessed whether betel quid
      chewing is an independent risk factor for field cancerization in OSCC patients.
      METHODS: We retrospectively examined the records of 1570 OSCC patients who
      underwent radical tumor resection between 1996 and 2011. A total of 1243 study
      participants (79%) had a positive history of betel quid chewing before surgery.
      Of the 767 patients treated with surgery alone, 599 (78%) were preoperative
      chewers, whereas a history of preoperative betel quid chewing was identified in
      644 (80%) of the 803 patients who received adjuvant therapy. The 5-year control,
      survival, and second primary tumors (SPTs) rates served as the main outcome
      measures. RESULTS: Regardless of the treatment modality, more than 70% of the
      SPTs were located in the oral cavity or soft palate. Despite a similar risk
      profile in terms of tumor depth, lymph node metastasis, and pathological margin
      status, preoperative chewers showed a significantly higher incidence of 5-year
      SPTs and local recurrences compared with non-chewers. Moreover, multivariate
      analysis demonstrated that preoperative betel quid chewing was an independent
      prognostic factor for 5-year local control and SPTs occurrence rates.
      CONCLUSIONS: Our results demonstrate that preoperative betel quid chewers had a
      higher incidence of local recurrence and SPTs than non-chewers, suggesting that
      field cancerization may occur in OSCC patients with a history of betel quid
      chewing.

PMID- 24882502
TI  - Sex differences in autism spectrum disorder based on DSM-5 criteria: evidence
      from clinician and teacher reporting.
AB  - In the absence of intellectual impairment autism spectrum disorder (ASD) is
      diagnosed both less and later in females. This study used clinician and teacher
      report to explore sex differences in the behavioural presentation of 69 girls and
      69 boys all diagnosed with high-functioning ASD. Evidence from DSM-IV-TR and DSM
      5 are presented. Sex differences in teacher concerns were also explored. While no
      sex differences were found in the broad social criteria presented in the DSM-IV
      TR or DSM-5, numerous differences were evident in how boys and girls came to meet
      each criterion. For example, girls were more likely to show an ability to
      integrate non-verbal and verbal behaviours, maintain a reciprocal conversation,
      and be able to initiate, but not maintain friendships. Moreover, girls presented
      with both less and different restricted interests. Teachers also reported
      substantially fewer concerns for girls than boys, including for externalising
      behaviours and social skills. Results suggest girls with ASD may present with a
      surface-level 'look' different from the 'classic' presentation of ASD, and
      present as less impaired when in a school setting. Consequently, results provide
      insight in to why the disorder may be more difficult to detect in cognitively
      able girls. 

PMID- 24882503
TI  - Child ADHD and ODD behavior interacts with parent ADHD symptoms to worsen
      parenting and interparental communication.
AB  - Attention-deficit hyperactivity disorder (ADHD) in children and adults increases
      risk of parenting difficulties and interparental discord. However, little is
      known about whether disruptive child behavior and adult ADHD operate additively
      or synergistically to predict parenting and interparental relationship quality.
      As part of a larger study, 90 parent couples were randomly assigned to interact
      with a 9-12 year-old confederate child exhibiting either ADHD/ODD-like behavior
      or typical behavior. Before these interactions, parents reported their own ADHD
      symptoms. Afterwards, parents reported on their partner's parenting and
      interparental communication behavior. Observers coded the parenting and
      communication behavior of both partners during the tasks. Child ADHD/ODD-like
      behavior was found to predict less positive and more negative parenting and
      communication reported by partners and observers beyond adult ADHD symptoms and
      other covariates. Elevated adult ADHD symptoms only uniquely increased risk of
      observer-coded negative parenting. Child and adult ADHD behavior interacted
      synergistically to predict partner-reported negative parenting and interparental
      communication, such that parents reporting greater ADHD symptoms-especially
      inattentiveness-were rated by their partners as parenting and communicating more
      negatively when managing child ADHD/ODD-like behavior than parents with fewer
      ADHD symptoms or those managing typical child behavior. Child and adult ADHD
      behavior did not interact to predict observer-coded parenting or interparental
      communication, and patterns did not differ for mothers or fathers. Our results
      underscore the potential risk of parents with elevated ADHD symptoms parenting
      and communicating negatively, at least as perceived by their partners, during
      interactions with children exhibiting ADHD/ODD behavior.

PMID- 24882504
TI  - Bullying victimisation, internalising symptoms, and conduct problems in South
      African children and adolescents: a longitudinal investigation.
AB  - Bullying victimisation has been prospectively linked with mental health problems
      among children and adolescents in longitudinal studies in the developed world.
      However, research from the developing world, where adolescents face multiple
      risks to social and emotional development, has been limited by cross-sectional
      designs. This is the first longitudinal study of the psychological impacts of
      bullying victimisation in South Africa. The primary aim was to examine
      prospective relationships between bullying victimisation and internalising and
      externalising symptoms in South African youth. Secondary aims were to examine
      gender and age-related differences in experiences of bullying victimisation.
      Children and adolescents (10-17 years, 57 % female, n = 3,515) from high HIV
      prevalent (>30 %) communities in South Africa were interviewed and followed-up 1
      year later (97 % retention). Census enumeration areas were randomly selected from
      urban and rural sites in two provinces and door-to-door sampling included all
      households with a resident child/adolescent. Exposure to multiple experiences of
      bullying victimisation at baseline predicted internalising symptoms and conduct
      problems 1 year later. Additionally, baseline mental health scores predicted
      later bullying victimisation, demonstrating bi-directionality of relationships
      between bullying victimisation and mental health outcomes in this sample.
      Expected gender differences in physical, verbal, and relational bullying
      victimisation were evident and predicted declines in bullying victimisation over
      time were observed. In the developed world, school-based anti-bullying programmes
      have been shown to be effective in reducing bullying and victimisation. Anti
      bullying programmes should be implemented and rigorously evaluated in South
      Africa, as this may promote improved mental health among South African children
      and adolescents. 

PMID- 24882505
TI  - Phase 4 left septal fascicular block.

PMID- 24882507
TI  - Primary prevention PVI for atrial fibrillation--weighing the risks and benefits.

PMID- 24882506
TI  - Low rate of cardiac events in first-degree relatives of diagnosis-negative young
      sudden unexplained death syndrome victims during follow-up.
AB  - BACKGROUND: Sudden unexplained death syndrome (SUDS) in young individuals often
      results from inherited cardiac disease. Accordingly, comprehensive examination in
      surviving first-degree relatives unmasks such disease in approximately 35% of the
      families. It is unknown whether individuals from diagnosis-negative families are
      at risk of developing manifest disease or cardiac events during follow-up.
      OBJECTIVE: This study aimed to study the prognosis of first-degree relatives of
      young SUDS victims, in whom the initial cardiologic and genetic examination did
      not lead to a diagnosis. METHODS: We retrieved vital status of surviving first
      degree relatives from 83 diagnosis-negative families who presented to our
      cardiogenetics department between 1996 and 2009 because of SUDS in >=1 relatives
      aged 1-50 years. Moreover, we contacted relatives who previously visited our
      center for detailed information. RESULTS: We obtained detailed information
      (median follow-up 6.6 years; interquartile range 4.7-9.6 years) in 340 of 417
      first-degree relatives (81.5%) from 77 of 83 families (92.8%). Vital status,
      available in 405 relatives (97.1%), showed that 20 relatives (4.9%) died during
      follow-up, including 1 natural death before the age of 50. This girl belonged to
      a family with multiple cases of idiopathic ventricular fibrillation and SUDS,
      including another successfully resuscitated sibling during follow-up. Two hundred
      thirty-four of 340 first-degree relatives (68.8%) underwent cardiologic
      examination. Of these, 76 (32.5%) were reevaluated. Inherited cardiac disease was
      diagnosed in 3 families (3.6%). CONCLUSION: In first-degree relatives of young
      SUDS victims with no manifest abnormalities during the initial examination, the
      risk of developing manifest inherited cardiac disease or cardiac events during
      follow-up is low. This does not apply to families with obvious familial SUDS.

PMID- 24882508
TI  - Unmasking of familial long QT syndrome type 2 with crystal methamphetamine
      exposure.

PMID- 24882509
TI  - Epicardial fat tissue thickness is correlated with diminished levels of co-enzyme
      Q10, a major antioxidant molecule among hemodialysis patients.
AB  - OBJECTIVES: Accelerated atherosclerosis is the major cause of mortality in
      patients on chronic maintenance hemodialysis (HD). Epicardial fat tissue (EFT) is
      a new risk factor in cardiovascular disease (CVD). The aim of this study was to
      evaluate the relation between plasma coenzyme Q10 levels (Co-Q10) which is a
      potent physiologic antioxidant and EFT thickness in HD patients. DESIGN AND
      METHODS: Seventy one chronic HD patients and 65 age and sex matched healthy
      individuals were included in the study. Plasma Co-Q10 levels were performed by
      high-performance liquid chromatography (HPLC) measurements. EFT was measured by
      transthoracic echocardiograpy (TTE) performed with a VIVID 7 instrument. RESULTS:
      Plasma Co-Q10 levels (1.36+/-0.43 vs 2.53+/-0.55, p<0.001) were significantly
      lower in HD patients compared to controls. EFT was significantly increased in HD
      patients compared to healthy controls (6.53+/-1.01 vs. 5.79+/-1.06 mm
      respectively, p<0.001). Correlation analysis showed that plasma Co-Q10 levels
      were inversely correlated with EFT (r=-0.263, p<0.05). Multiple linear regression
      analysis was used to define independent determinants of EFT in HD patients.
      According to linear regression analysis, age, BMI, total cholesterol and Co-Q10
      levels were found to be independent predictors of EFT (adjusted r(2)=0.38,
      p<0.001). CONCLUSION: This study demonstrated that EFT thickness was
      significantly higher among HD patients compared to healthy controls. In addition;
      this study was the first to demonstrate an inverse correlation between EFT
      thickness and Co-Q10 levels in this patient population.

PMID- 24882510
TI  - Illuminating and alarming insights into vascular healing.

PMID- 24882511
TI  - Analysis by optical coherence tomography of long-term arterial healing after
      implantation of different types of stents.
AB  - BACKGROUND: Although drug-eluting stents have significantly reduced the midterm
      incidence of target lesion revascularization (TLR), in vivo studies on long-term
      vessel healing of sirolimus-eluting stents (SESs) and paclitaxel-eluting stents
      (PESs) are limited. The aim of this study was to compare long-term arterial
      healing with SESs and PESs. METHODS: We evaluated 27 SESs (23 patients) and 21
      PESs (20 patients) by serial optical coherence tomography at 6 months (midphase)
      and >= 3 years (late phase) after stenting and evaluated the change of neointimal
      thickness (NIT), the percentages of uncovered and malapposed struts, peristrut
      low-intensity area (region around stent struts with a homogeneously lower
      intensity appearance than surrounding tissue), thrombus, and atherogenic
      neointima. RESULTS: At follow-up, most SESs showed a progressive increase in the
      average NIT, whereas PESs showed variable changes. Between midphase and late
      phase, NIT increased significantly in SESs (midphase, 94.1 +/- 49.3; late phase,
      130.2 +/- 78.7; P = 0.001) but decreased significantly in PESs (midphase, 167.4
      +/- 122.9; late phase, 136.0 +/- 77.7; P = 0.04). The percentages of uncovered
      struts decreased significantly in SESs; conversely, variable changes were
      observed in PESs. Peristrut low-intensity area and thrombus formation decreased
      in SESs but remained largely unchanged in PESs. The prevalence of atherogenic
      neointima was greater in the late phase than in the midphase in both groups but
      was similar for both stents. CONCLUSIONS: Long-term vessel healing was different
      for SESs and PESs. Progressive vessel healing was consistently observed in SESs,
      whereas a heterogeneous process of delayed vessel healing was noted for PESs.

PMID- 24882512
TI  - Simeprevir for the treatment of chronic hepatitis C genotype 1 infection.
AB  - Simeprevir is a second-wave hepatitis C virus NS3/4A protease inhibitor that was
      designed to optimize its antiviral activity, safety, drug-drug interactions, and
      pharmacokinetic profile. When used to treat patients with hepatitis C virus
      genotype 1, simeprevir is coadministered with peginterferon and ribavirin for 12
      weeks, followed by double therapy with Peg-IFN and ribavirin for an additional 12
      or 36 weeks. Phase III studies achieved a sustained virologic response in 80-90%
      of treatment-naive patients (International Phase III studies QUEST-1/2: 80/81%;
      Japanese Phase III trial CONCERTO-1: 89%). Unlike with the first protease
      inhibitors, telaprevir or boceprevir, used in triple therapy, when using
      simeprevir the frequency of clinically problematic adverse events such as anemia,
      rash, and digestive symptoms is almost comparable to that of double therapy. The
      advent of simeprevir has enabled interferon therapy, which started as monotherapy
      in early 1990s, to reach its maximum efficacy and arrive at what can be
      considered its final form at least in genotype 1b. 

PMID- 24882513
TI  - Carbohydrate radicals: from ethylene glycol to DNA strand breakage.
AB  - Radiation-induced DNA strand breakage results from the reactions of radicals
      formed at the sugar moiety of DNA. In order to elucidate the mechanism of this
      reaction investigations were first performed on low molecular weight model
      systems. Results from studies on deoxygenated aqueous solutions of ethylene
      glycol, 2-deoxy-d-ribose and other carbohydrates and, more relevantly, of d
      ribose-5-phosphate have shown that substituents can be eliminated from the beta
      position of the radical site either proton and base-assisted (as in the case of
      the OH substituent), or spontaneously (as in the case of the phosphate
      substituent). In DNA the C(4') radical undergoes strand breakage via this type of
      reaction. In the presence of oxygen the carbon-centred radicals are rapidly
      converted into the corresponding peroxyl radicals. Again, low molecular weights
      models have been investigated to elucidate the key reactions. A typical reaction
      of DNA peroxyl radicals is the fragmentation of the C(4')-C(S') bond, a reaction
      not observed in the absence of oxygen. Although OH radicals may be the important
      direct precursors of the sugar radicals of DNA, results obtained with poly(U)
      indicate that base radicals may well be of even greater importance. The base
      radicals, formed by addition of the water radicals (H and OH) to the bases would
      in their turn attack the sugar moiety to produce sugar radicals which then give
      rise to strand breakage and base release. For a better understanding of strand
      break formation it is therefore necessary to investigate in more detail the
      reactions of the base radicals. For a start, the radiolysis of uracil in
      oxygenated solutions has been reinvestigated, and it has been shown that the
      major peroxyl radical in this system undergoes base-catalysed elimination of
      [Formula: see text], a reaction that involves the proton at N(l). In the nucleic
      acids the pyrimidines are bound at N(l) to the sugar moiety and this type of
      reaction can no longer occur. Therefore, with respect to the nucleic acids,
      pyrimidines are good models only in acid solutions where the [Formula: see text]
      elimination reaction is too slow to compete with the bimolecular reactions of the
      peroxyl radicals. Moreover, the long lifetime of the radical sites on the nucleic
      acid strand may allow reactions to occur which are kinetically of first order,
      and which cannot be studied in model systems at ordinary dose rates. It is
      therefore suggested to extend model system studies to low dose rates and to
      oligonucleo-tides. Such studies might eventually reveal the key reactions in
      radical-induced DNA degradation.

PMID- 24882517
TI  - Analysis of pancreatic endocrine function in patients with IgG4-related diseases,
      in whom autoimmune pancreatitis was ruled out by diagnostic imaging.
AB  - IgG4-related disease (IgG4RD) is a newly recognized systemic disease
      characterized by the elevation of serum IgG4 levels and abundant IgG4-positive
      plasma cell infiltration into the involved organs. Few data exist regarding the
      relationship between diabetes or glucose intolerance and IgG4RD in the absence of
      obvious type 1 autoimmune pancreatitis (AIP). Therefore, we are characterizing
      pancreatic endocrine function in IgG4RD patients with no signs of type 1 AIP. 28
      patients (12 men, mean age 62.1 years old) were diagnosed as having IgG4RD from
      serum IgG4 levels, histopathology and images. Diagnostic imaging ruled out
      obvious type 1AIP. We used 75g oral glucose tolerance tests (OGTT) and arginine
      tolerance tests (ATT) to evaluate pancreatic endocrine function. Patients' serum
      IgG4 and HbA1c levels were 603+/-437 mg/dL and 6.6+/-1.0%, respectively. The
      results of OGTT on 23 patients showed that 12 patients had diabetes, 4 had
      impaired glucose tolerance, and 7 had normal glucose tolerance. Interestingly,
      insulin secretion was preserved in most of the patients, even in diabetic
      patients, on OGTT and ATT. Glucagon hyperreactivity was observed in 10 of the 19
      patients who underwent ATT. Twenty-three patients were treated for IgG4RD with
      glucocorticoids. Their HbA1c levels were significantly elevated during the first
      six months of treatment, but improved after twelve months in parallel with
      glucocorticoid therapy. These results demonstrate the high frequency of
      pancreatic endocrine dysfunction in IgG4RD even when there is no indication of
      AIP, thus revealing that pancreatic endocrine dysfunction frequently occurs in
      IgG4RD without obvious type 1 AIP. 

PMID- 24882515
TI  - Hippo-independent activation of YAP by the GNAQ uveal melanoma oncogene through a
      trio-regulated rho GTPase signaling circuitry.
AB  - Mutually exclusive activating mutations in the GNAQ and GNA11 oncogenes, encoding
      heterotrimeric Galphaq family members, have been identified in ~ 83% and ~ 6% of
      uveal and skin melanomas, respectively. However, the molecular events underlying
      these GNAQ-driven malignancies are not yet defined, thus limiting the ability to
      develop cancer-targeted therapies. Here, we focused on the transcriptional
      coactivator YAP, a critical component of the Hippo signaling pathway that
      controls organ size. We found that Galphaq stimulates YAP through a Trio-Rho/Rac
      signaling circuitry promoting actin polymerization, independently of
      phospholipase Cbeta and the canonical Hippo pathway. Furthermore, we show that
      Galphaq promotes the YAP-dependent growth of uveal melanoma cells, thereby
      identifying YAP as a suitable therapeutic target in uveal melanoma, a GNAQ/GNA11
      initiated human malignancy.

PMID- 24882518
TI  - Sarcomatoid carcinoma of the kidney in a MEN1 patient: case report and genetic
      profile.
AB  - Renal tumors are exceedingly rare in Multiple Endocrine Neoplasia type 1 (MEN1),
      a pleyotropic hereditary cancer disorder affecting the endocrine system. Herein
      we report a unique case of renal sarcomatoid carcinoma with concomitant
      ipsilateral non-secreting adrenal adenoma occurring in a young male MEN1 patient,
      previously operated for hyperparathyroidism and multiple pancreatic
      neuroendocrine neoplasms. Molecular analysis in the MEN1 locus at 11q13 showed
      loss of heterozygosity in the adrenal lesion, while kidney cancer was unrelated
      to MEN1 syndrome. 

PMID- 24882519
TI  - Triangular-shaped molecular random tiling and molecular rotation in two
      dimensional glassy networks.
AB  - Macrocycle-1 molecules can self-assemble into glassy state networks via van der
      Waals force and form many triangular nanopores in networks. The nanopores can be
      expressed by triangular tilings, which lead to a particularly rich range of
      arrangements. Moreover an interesting molecular rotation phenomenon was observed
      in the glassy networks.

PMID- 24882516
TI  - Mutant Gq/11 promote uveal melanoma tumorigenesis by activating YAP.
AB  - Uveal melanoma (UM) is the most common cancer in adult eyes. Approximately 80% of
      UMs harbor somatic activating mutations in GNAQ or GNA11 (encoding Gq or G11,
      respectively). Herein, we show in both cell culture and human tumors that cancer
      associated Gq/11 mutants activate YAP, a major effector of the Hippo tumor
      suppressor pathway that is also regulated by G protein-coupled receptor
      signaling. YAP mediates the oncogenic activity of mutant Gq/11 in UM development,
      and the YAP inhibitor verteporfin blocks tumor growth of UM cells containing
      Gq/11 mutations. This study reveals an essential role of the Hippo-YAP pathway in
      Gq/11-induced tumorigenesis and suggests YAP as a potential drug target for UM
      patients carrying mutations in GNAQ or GNA11. 

PMID- 24882520
TI  - Towards the development of clinical measures for spinal cord injury based on the
      International Classification of Functioning, Disability and Health with Rasch
      analyses.
AB  - OBJECTIVES: To determine whether the International Classification of Functioning,
      Disability and Health (ICF) categories relevant to spinal cord injury (SCI) can
      be integrated in clinical measures and to obtain insights to guide their future
      operationalization. Specific aims are to find out whether the ICF categories
      relevant to SCI fit a Rasch model taking into consideration the dimensionality
      found in previous investigations, local item dependencies, or differential item
      functioning. DESIGN: All second-level ICF categories collected in the Development
      of ICF Core Sets for SCI project in specialized centers within 15 countries from
      2006 through 2008. SETTING: Secondary data analysis. PARTICIPANTS: Adults
      (N=1048) with SCI from the early postacute and long-term living context.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Two unidimensional Rasch
      analyses: one for the ICF categories from body functions and body structures
      components and another for the ICF categories from the activities and
      participation component. RESULTS: Results support good reliability and targeting
      of the ICF categories in both dimensions. In each dimension, few ICF categories
      were subject to misfit. Local item dependency was observed between ICF categories
      of the same chapters. Group effects for age and sex were observed only to a small
      extent. CONCLUSIONS: The validity of ICF categories to develop measures of
      functioning in SCI for clinical practice and research is to some extent
      supported. Model adjustments were suggested to further improve their
      operationalization and psychometrics.

PMID- 24882521
TI  - Durable defense: robust and varied attachment of non-leaching poly"-onium"
      bactericidal coatings to reactive and inert surfaces.
AB  - Developing antimicrobial coatings to eliminate biotic contamination is a critical
      need for all surfaces, including medical, industrial, and domestic materials. The
      wide variety of materials used in these fields, from natural polymers to metals,
      require coatings that not only are antimicrobial, but also contain different
      surface chemistries for covalent immobilization. Alkyl "-onium" salts are potent
      biocides that have defied bacterial resistance mechanisms when confined to an
      interface. In this feature article, we highlight the various methods used to
      covalently immobilize bactericidal polymers to different surfaces and further
      examine the mechanistic aspects of biocidal action with these surface bound poly"
      onium" salts. 

PMID- 24882522
TI  - Observation of active sites for oxygen reduction reaction on nitrogen-doped
      multilayer graphene.
AB  - Active sites and the catalytic mechanism of nitrogen-doped graphene in an oxygen
      reduction reaction (ORR) have been extensively studied but are still
      inconclusive, partly due to the lack of an experimental method that can detect
      the active sites. It is proposed in this report that the active sites on nitrogen
      doped graphene can be determined via the examination of its chemical composition
      change before and after ORR. Synchrotron-based X-ray photoelectron spectroscopy
      analyses of three nitrogen-doped multilayer graphene samples reveal that oxygen
      reduction intermediate OH(ads), which should chemically attach to the active
      sites, remains on the carbon atoms neighboring pyridinic nitrogen after ORR. In
      addition, a high amount of the OH(ads) attachment after ORR corresponds to a high
      catalytic efficiency and vice versa. These pinpoint that the carbon atoms close
      to pyridinic nitrogen are the main active sites among the different nitrogen
      doping configurations.

PMID- 24882523
TI  - Identifying maternity services in public hospitals in rural and remote Australia.
AB  - OBJECTIVE: This paper articulates the importance of accurately identifying
      maternity services. It describes the process and challenges of identifying the
      number, level and networks of rural and remote maternity services in public
      hospitals serving communities of between 1000 and 25000 people across Australia,
      and presents the findings of this process. METHODS: Health departments and the
      national government's websites, along with lists of public hospitals, were used
      to identify all rural and remote Australian public hospitals offering maternity
      services in small towns. State perinatal reports were reviewed to establish
      numbers of births by hospital. The level of maternity services and networks of
      hospitals within which services functioned were determined via discussion with
      senior jurisdictional representatives. RESULTS: In all, 198 rural and remote
      public hospitals offering maternity services were identified. There were
      challenges in sourcing information on maternity services to generate an accurate
      national picture. The nature of information about maternity services held
      centrally by jurisdictions varied, and different frameworks were used to describe
      minimum requirements for service levels. Service networks appeared to be based on
      a combination of individual links, geography and transport infrastructure.
      CONCLUSIONS: The lack of readily available centralised and comparable information
      on rural and remote maternity services has implications for policy review and
      development, equity, safety and quality, network development and planning.
      Accountability for services and capacity to identify problems is also
      compromised.

PMID- 24882524
TI  - Intima-media thickness measurements in the fetus and mother during pregnancy: a
      feasibility study.
AB  - Fetal intima-media thickness (IMT) has been suggested as a marker of pre-clinical
      atherosclerosis, and maternal IMT could be altered through dynamic circumstances
      related to pregnancy. We investigated the feasibility of measurement of IMT at
      four pre-defined fetal and four pre-defined maternal arterial locations to
      determine vascular changes that could be associated with impaired vascular
      function. IMT was measured from the first to third trimester (12-34 wk), in 38
      low-risk pregnancies. We imaged a 10-mm region of interest using a Mindray
      (Shenzhen, China) high-resolution ultrasound machine with automated IMT
      measurement software. Fetal abdominal aorta IMT was measurable during the second
      trimester in 71% and during the third trimester in 100% of the case, and
      umbilical artery IMT was measurable in 50% and 82% of cases during the second and
      third trimesters, respectively. Fetal IMT measurements were not possible during
      the first trimester. It was not often feasible to measure the IMT of the fetal
      common carotid artery, fetal renal artery and maternal iliac artery (maximal 20%
      of cases). Maternal common carotid artery, abdominal aorta and uterine artery
      IMTs were measurable throughout pregnancy. There was a significant relation
      between gestational age and IMT in the umbilical artery (p = 0.03) and a
      significant relation between body mass index and IMT in the maternal common
      carotid artery (p = 0.01). IMT measurements are feasible in some maternal and
      fetal vessels of interest. Further studies are underway to obtain more insight
      into vascular development during normal and pathologic pregnancies.

PMID- 24882525
TI  - Interactions between individual ultrasound-stimulated microbubbles and fibrin
      clots.
AB  - The use of ultrasound-stimulated microbubbles (USMBs) to promote thrombolysis is
      well established, but there remains considerable uncertainty about the mechanisms
      of this process. Here we examine the microscale interactions between individual
      USMBs and fibrin clots as a function of bubble size, exposure conditions and clot
      type. Microbubbles (n = 185) were placed adjacent to clot boundaries ("coarse" or
      "fine") using optical tweezers and exposed to 1-MHz ultrasound as a function of
      pressure (0.1-0.39 MPa). High-speed (10 kfps) imaging was employed, and clots
      were subsequently assessed with 2-photon microscopy. For fine clots, 46% of
      bubbles "embedded" within 10 MUm of the clot boundary at pressures of 0.1 and 0.2
      MPa, whereas at 0.39 MPa, 53% of bubbles penetrated and transited into the clots
      with an incidence inversely related to their diameter. A substantial fraction of
      penetrating bubbles induced fibrin network damage and promoted the uptake of
      nanobeads. In coarse clots, penetration occurred more readily and at lower
      pressures than in fine clots. The results therefore provide direct evidence of
      therapeutically relevant effects of USMBs and indicate their dependence on size,
      exposure conditions and clot properties.

PMID- 24882526
TI  - Synthesis and electrochemistry of beta-pyrrole nitro-substituted cobalt(II)
      porphyrins. The effect of the NO2 group on redox potentials, the electron
      transfer mechanism and catalytic reduction of molecular oxygen in acidic media.
AB  - Four cobalt(II) porphyrins, two of which contain a beta-pyrrole nitro
      substituent, were synthesized and characterized by electrochemistry and
      spectroelectrochemistry. The investigated compounds are represented as (TRPP)Co
      and (NO2TRPP)Co, where TRPP is the dianion of a substituted tetraphenylporphyrin
      and R is a CH3 or OCH3 substituent on the four phenyl rings of the macrocycle.
      Two reductions and three oxidations are observed for each compound in CH2Cl2
      containing 0.10 M tetra-n-butylammonium perchlorate. The first reduction of the
      compounds without a nitro substituent is metal-centered and leads to formation of
      a Co(I) porphyrin which then reacts with the CH2Cl2 solvent to generate a carbon
      sigma-bonded Co(III)-R complex. A further reduction then occurs at more negative
      potentials to generate an unstable Co(II) sigma-bonded compound. In contrast to
      these reactions, the first reduction of the nitro-substituted porphyrins is
      macrocycle-centered under the same solution conditions and gives a Co(II)
      porphyrin pi-anion radical product. This reversible electron transfer is then
      followed at more negative potentials by a second reversible one-electron addition
      to give a Co(II) dianion. Three reversible one-electron oxidations are also seen
      for each compound. The first is metal-centered and the next two involve the
      conjugated pi-system of the macrocycle. Each neutral Co(II) porphyrin was also
      examined as to its catalytic activity for electroreduction of molecular oxygen
      when coated on an edge-plane pyrolytic graphite electrode in 1.0 M HClO4. The
      beta-pyrrole nitro-substituted derivatives were shown to be better catalysts than
      the non-nitro substituted compounds under the utilized experimental conditions.

PMID- 24882527
TI  - Mass effect and signal intensity alteration in the suprapatellar fat pad:
      associations with knee symptoms and structure.
AB  - OBJECTIVE: To describe cross-sectional associations between mass effect or signal
      intensity alteration of the suprapatellar fat pad (SPFP) with knee symptoms and
      structure in older adults. METHODS: A cross-sectional sample of 904 randomly
      selected subjects (mean 62.4 years, 49.9% female) was studied. T1- or T2-weighted
      fat suppressed magnetic resonance imaging (MRI) was used to assess mass effect or
      signal intensity alteration of SPFP, cartilage volume, cartilage defects, and
      bone marrow lesions (BMLs). Knee pain was assessed by self-administered Western
      Ontario McMaster Osteoarthritis Index (WOMAC) questionnaire. The Osteoarthritis
      Research Society International (OARSI) atlas was used to assess knee osteophyte,
      joint space narrowing (JSN) and radiographic osteoarthritis (ROA). Univariable
      and multivariable linear or logistic regression analyses were used to examine the
      associations. RESULTS: After adjustment for confounders including age, sex, body
      mass index (BMI), disease status, tibial bone area and/or ROA, the presence of
      SPFP mass effect was significantly associated with any knee pain (OR: 2.39; 95%
      confidence interval (CI): 1.54, 3.70) and ROA (OR: 2.10; 95% CI: 1.33, 3.31) but
      not with cartilage volume, cartilage defects or BMLs. The presence of SPFP signal
      intensity alteration was significantly associated with any knee pain (OR: 1.90;
      95% CI: 1.43, 2.53), ROA (OR: 1.83; 95% CI: 1.37, 2.45), any BMLs (OR: 1.55; 95%
      CI: 1.17, 2.06) but not with cartilage volume and cartilage defects. Significant
      associations with knee pain and BMLs were more evident in subjects with ROA.
      Presence of SPFP mass effect and/or signal intensity alteration combined was
      associated with any tibial cartilage defects (OR: 1.45; 95% CI: 1.04, 2.04).
      CONCLUSIONS: SPFP mass effect and/or signal intensity alterations are
      deleteriously associated with knee pain, radiographic OA and BMLs in this cross
      sectional study, suggesting that SPFP abnormalities may contribute to pain and
      structural abnormalities in the knee.

PMID- 24882528
TI  - Canadian Cardiovascular Society position statement on the management of thoracic
      aortic disease.
AB  - This Canadian Cardiovascular Society position statement aims to provide succinct
      perspectives on key issues in the management of thoracic aortic disease (TAD).
      This document is not a comprehensive overview of TAD and important elements of
      the epidemiology, presentation, diagnosis, and management of acute aortic
      syndromes are deliberately not discussed; readers are referred to the 2010
      guidelines published by the American Heart Association, American College of
      Cardiology, American Association for Thoracic Surgery, and other stakeholders.
      Rather, this document is a practical guide for clinicians managing adult patients
      with TAD. Topics covered include size thresholds for surgical intervention,
      emerging therapies, imaging modalities, medical and lifestyle management, and
      genetics of TAD. The primary panel consisted of experts from a variety of
      disciplines that are essential for comprehensive management of TAD patients. The
      methodology involved a focused literature review with an emphasis on updates
      since 2010 and the use of Grading of Recommendations Assessment, Development, and
      Evaluation methodology to arrive at specific recommendations. The final document
      then underwent review by a secondary panel. This document aims to provide
      recommendations for most patients and situations. However, the ultimate judgement
      regarding the management of any individual patients should be made by their
      health care team. 

PMID- 24882529
TI  - Greater mortality risk among patients with delayed follow-up after implantable
      cardioverter defibrillator procedures.
AB  - BACKGROUND: Substantial numbers of deaths occur among implantable cardioverter
      defibrillator (ICD) recipients. Timely follow-up after ICD implantation might
      improve patient outcomes. Our objective was to examine follow-up care and
      outcomes among patients undergoing ICD implantation. METHODS: We compared patient
      characteristics and outcomes of those with late (> 12 weeks) vs early
      defibrillator clinic follow-up after ICD implantation in the Ontario ICD Database
      from 2007 to 2011. We examined the effect of ICD clinic follow-up visits after
      implant compared with primary care physician tracer on mortality outcomes using
      time-varying covariate analyses. RESULTS: Among 8096 ICD recipients (age 64.6 +/-
      12.6 years), 1145 (14%) received delayed follow-up. Patients with early ICD
      clinic follow-up experienced reduced risk of all-cause mortality, with a hazard
      ratio [HR] of 0.69 (95% confidence interval [CI], 0.50-0.95; P = 0.023) adjusted
      for clinical factors, primary care visits after discharge, and distance to follow
      up centre. Early ICD clinic follow-up was associated with a reduction in out-of
      hospital death with adjusted HR of 0.52 (95% CI, 0.36-0.76; P = 0.001) but not
      with a significant change in cardiovascular hospitalizations. In a tracer
      analysis, early primary care physician follow-up was associated with a
      nonsignificant trend toward increased mortality with an adjusted HR of 1.48 (95%
      CI, 0.97-2.25; P = 0.072). Reduced estimated glomerular filtration rate,
      secondary prevention or replacement devices, myocardial ischemia, smoking, and
      greater geographic distance to the implanting centre increased the odds of
      delayed follow-up. CONCLUSIONS: After device implantation, early defibrillator
      clinic follow-up was associated with reduced risk of all-cause and out-of
      hospital death compared with those experiencing delayed follow-up.

PMID- 24882530
TI  - Predictors of advanced His-Purkinje conduction disturbances in patients with
      unexplained syncope and bundle branch block.
AB  - BACKGROUND: For patients presenting with syncope and bundle branch block (BBB),
      results during electrophysiological studies (EPS) might depend on the
      electrocardiographic pattern of conduction disturbances. We sought to identify
      predictors of advanced His-Purkinje conduction disturbances (HPCDs) in these
      patients. METHODS: In this retrospective multicentre study, patients were
      included who: (1) presented with unexplained syncope; (2) had BBB (QRS duration
      >= 120 ms); and (3) were investigated with EPS. HPCD was diagnosed if the
      baseline His-ventricular interval was >= 70 ms or if second- or third-degree His
      Purkinje block was observed during atrial pacing or pharmacological challenge.
      RESULTS: Of the 171 patients studied (72 +/- 13 years, 64% male sex, mean left
      ventricular ejection fraction 57 +/- 9%), advanced HPCD was found in 73 patients
      (43%). The following electrocardiographic features were associated with HPCD (P =
      0.01): isolated right BBB (34.4%), right BBB with left anterior fascicular block
      (36.4%), left BBB (46.2%), and right BBB with left posterior fascicular block
      (LPFB, 78.6%). Multivariate analysis identified first-degree atrioventricular
      block (odds ratio, 2.4; 95% confidence interval, 1.2-4.7; P = 0.01) and LPFB
      (odds ratio, 4.8; 95% confidence interval, 1.3-18.5; P = 0.02) as the only 2
      independent predictors of advanced HPCD. CONCLUSIONS: For patients presenting
      with syncope and BBB, first-degree atrioventricular block and LPFB increased the
      likelihood of finding HPCDs during EPS. However, no single electrocardiographic
      feature could consistently predict the outcome of EPS, so this investigation is
      still necessary in assessing the need for pacemaker implantation, irrespective of
      the precise appearance of abnormalities on ECG.

PMID- 24882531
TI  - Determinants of early readmission after hospitalization for heart failure.
AB  - BACKGROUND: Determination of factors increasing the likelihood of early
      readmission after hospitalization for heart failure (HF) is fundamental for
      identifying potential targets for intervention. Thus, we studied the
      characteristics of patients readmitted within 7 and 30 days after hospitalization
      for HF in Alberta, Canada. METHODS: Using hospital discharge abstract data, we
      followed patients with incident HF discharged from April 2004-March 2012 and
      determined their readmission status within 7 and 30 days after an index
      hospitalization. Logistic regression was used to determine variables associated
      with readmission. RESULTS: Of 18,590 patients with HF (49.8% women; mean age 76.4
      years), 5.6% were readmitted within 7 days and 18% were readmitted within 30
      days. Readmission rates within 7 and 30 days increased significantly with age.
      Seven-day all-cause readmissions were associated with history of kidney disease
      (adjusted odds ratio [aOR], 1.28; 95% confidence interval [CI], 1.08-1.53), and
      30-day all-cause readmissions were associated with cancer, pulmonary, liver, and
      kidney disease. Discharge with home care services at the time of discharge was a
      risk factor for readmission within 7 days (aOR, 1.26; 95% CI, 1.07-1.49) and 30
      days (aOR, 1.23; 95% CI, 1.11-1.35). Discharge from a hospital with HF services
      was associated with lower readmission at both 7 days (aOR, 0.65; 95% CI, 0.57
      0.74) and 30 days (aOR, 0.71; 95% CI, 0.65-0.77). CONCLUSIONS: Several factors
      were associated with increased risk of readmission, whereas patients discharged
      from hospitals with HF services had a lower risk of readmission within 7 and 30
      days of discharge. The interaction of provision of home care and higher early
      readmission deserves further study.

PMID- 24882532
TI  - Mortality outcomes among status Aboriginals and whites with heart failure.
AB  - BACKGROUND: Aboriginals have more cardiovascular risk factors than do non
      Aboriginals that predispose them to the development of heart failure (HF).
      Whether long-term mortality outcomes and health care use differ between
      Aboriginals and whites with HF is unknown. METHODS: The population consisted of
      all Albertans aged >= 20 years with an incident HF hospitalization between 2000
      and 2008. Aboriginal status is recorded in the Alberta Health Care Insurance
      Registry and white ethnicity was determined using previously validated surname
      analysis algorithms. Cox and logistic regression was used to examine mortality
      outcomes after adjustment for key variables. RESULTS: Compared with whites (n =
      42,288), status aboriginal patients with HF (n = 1158) were significantly younger
      (mean age, 62.6 vs 75.4 years; P < 0.0001) and had higher rates of diabetes (45%
      vs 29%; P < 0.0001) and chronic obstructive pulmonary disease (40% vs 36%; P <
      0.0001) but lower rates of most other comorbidities. Although crude mortality
      rates were lower in status Aboriginals than in whites at 1 year (22% vs 31%; P <
      0.0001) and at 5 years (48% vs 59%; P < 0.0001), after adjustment, status
      Aboriginals exhibited increased mortality at 1 year (adjusted odds ratio [OR],
      1.18; 95% confidence interval [CI], 1.01-1.38) and 5 years (adjusted OR, 1.39;
      95% CI, 1.16-1.67). Compared with whites, status Aboriginals used more health
      care resources in the years before and after an incident HF hospitalization but
      less specialist care. CONCLUSIONS: Although status Aboriginals hospitalized for
      the first time with HF are > 10 years younger, they use more health care
      resources and have increased short- and long-term mortality compared with their
      white counterparts.

PMID- 24882533
TI  - Sedation, analgesia, and anaesthesia variability in laboratory-based cardiac
      procedures: an international survey.
AB  - BACKGROUND: There is a paucity of data regarding the type of anaesthesia used and
      the perception toward anaesthesia among cardiologists, anaesthesiologists, and
      nurses. Our objective was to describe the use of sedation during nonsurgical
      cardiac procedures. METHODS: We designed a Web-based survey to assess anaesthesia
      practices during cardiac procedures. The survey was distributed to cardiologists,
      anaesthesiologists, and nurses through national societies and international
      investigator networks. The questions addressed the type of practice, type of
      anaesthesia used during procedures, and perceptions regarding anaesthesia.
      RESULTS: The survey was completed by 497 participants. Sedation during cardiac
      catheterization was used by 77/84 (92%) of cardiologists in North America, but
      only by 46/121 (38%) in other countries (P < 0.0001). Use of general anaesthesia
      for complex procedures such as transaortic valve replacement is also more common
      in North America (92%) compared with other countries (76%; P = 0.004). Specific
      sedation-related training was provided to less than a third of
      nonanaesthesiologists. Although more than half of the nurses received training
      regarding procedural sedation, such training is provided to less than a quarter
      of the cardiologists. The lack of training was noted in all geographic regions.
      CONCLUSIONS: Anaesthesia and especially sedation is frequently used during
      percutaneous cardiac procedures. The rate of use and perceptions regarding
      sedation differs among professionals and might be influenced by culture,
      training, and geography. There is a lack of adequate formal training in the use
      of sedation and analgesia for nonanaesthesia professionals.

PMID- 24882534
TI  - Survival of patients <= 50 years of age after alcohol septal ablation for
      hypertrophic obstructive cardiomyopathy.
AB  - BACKGROUND: The long-term efficacy and safety of alcohol septal ablation (ASA)
      has recently been demonstrated. However, there is still debate about the outcome
      of younger patients who should be treated using myectomy, according to American
      College of Cardiology Foundation/American Heart Association guidelines. The aim
      of this study was to evaluate the long-term outcome of patients <= 50 years of
      age after ASA for hypertrophic obstructive cardiomyopathy (HOCM). METHODS: We
      retrospectively evaluated consecutive, highly symptomatic patients aged <= 50
      years with HOCM who underwent ASA. RESULTS: Institutional databases of 3
      cardiovascular centres identified 290 patients with HOCM who underwent ASA; 75
      (26%) of them were aged <= 50 years at the time of their first ASA. Median
      duration of follow-up was 5.1 years (range, 0.1-15.4 years). Four patients (5%)
      died during the study period (438 patient-years; the annual mortality rate was
      0.91%; 95% confidence interval [CI], 0.25-2.34%; the annual mortality rate
      combined with the first appropriate implantable cardioverter-defibrillator
      discharge was 1.43%; 95% CI, 0.52-3.10%). Survival free of all-cause mortality at
      1, 5, and 10 years was 97% (95% CI, 89-99%), 94% (95% CI, 84-98%), and 94% (95%
      CI, 84-98%), respectively. CONCLUSIONS: Results of this first study focused on
      HOCM patients aged <= 50 years who underwent ASA suggest a low risk of all-cause
      death or appropriate implantable cardioverter-defibrillator discharge in the long
      term follow-up.

PMID- 24882535
TI  - A novel system for transcatheter closure of patent foramen ovale: clinical and
      echocardiographic outcome comparison with other contemporary devices.
AB  - BACKGROUND: Effective closure performance for patent foramen ovale (PFO) has been
      suggested to be one of the factors that plays a relevant role in future clinical
      outcomes after stroke or transient ischemic attack. METHODS: Between January 2009
      and June 2012, all consecutive patients undergoing transcatheter PFO closure in
      our institution using the Amplatzer PFO Occluder (APO) (St Jude Medical, St Paul,
      MN), BioSTAR (NMT Medical Inc, Boston, MA), GORE HELEX (HELEX) (W.L. Gore &
      Associates, Newark, DE), and GORE Septal Occluder (GSO) (W.L. Gore & Associates)
      were included. Closure performance was assessed using transesophageal
      echocardiography 4 months after the index procedure. RESULTS: One hundred ninety
      three patients were included in the study. Patient distribution was as follows:
      (1) 48 GSO (24.8%); (2) 34 HELEX (17.6%); (3) 74 APO (38.3%); and (4) 37 BioSTAR
      (19.1%). No complications occurred during device implantation. During clinical
      follow-up (20.8 +/- 13.2 months), 2 (1.1%) patients had a stroke, 3 (1.7%)
      patients had a peripheral embolism, and 8 (4.7%) patients presented with a
      documented atrial arrhythmia. There were no significant differences in clinical
      outcomes among the devices. Transesophageal echocardiography follow-up revealed
      higher closure rates with GSO (92.6%) and BioSTAR (93.7%) compared with HELEX
      (74.2%; P = 0.031 and P = 0.034, respectively) and APO (76.4%; P = 0.036 and P =
      0.041, respectively). CONCLUSIONS: The GSO and BioSTAR showed better closure
      rates than HELEX and APO at 4 months. PFO closure is a safe procedure with a low
      rate of clinical events at follow-up.

PMID- 24882536
TI  - Antihypertensive drug prescribing and persistence among new elderly users:
      implications for persistence improvement interventions.
AB  - BACKGROUND: The objective of this study was to examine persistence rates and
      factors influencing persistence for new elderly users of antihypertensive drugs.
      METHODS: We conducted a population-based cohort study in Ontario of adults aged
      66 years or older to identify new users of antihypertensive medications between
      1999 and 2010. Two-year therapy and class persistence were defined as persistence
      on any antihypertensive medication and persistence only on the same
      antihypertensive medication class, respectively. RESULTS: From 1999-2010, the
      prevalence of antihypertensive drug use increased from 47.8%-60.5% (P < 0.0001).
      Persistence was evaluated in 420,148 new users of antihypertensive drugs. After 2
      years, therapy persistence was 58.9% and varied according to initial class
      prescribed, from 52.3% for diuretics to 64.1% for angiotensin-converting enzyme
      inhibitors. Class persistence ranged from 25.3% for diuretics to 35.8% for
      angiotensin II receptor blockers. Therapy persistence rates were greater in new
      users from more recent years (adjusted odds ratio [aOR], 1.24; 95% confidence
      interval [CI], 1.21-1.27). Subgroups that demonstrated poorer persistence
      included patients older than 75 years (aOR, 0.95; 95% CI, 0.94-0.96), those with
      lowest neighbourhood income quintile (aOR, 0.81; 95% CI, 0.80-0.83 compared with
      the highest quintile), those from urban vs rural areas (aOR, 0.83; 95% CI, 0.81
      0.84), and those who started on diuretics as initial monotherapy compared with
      all other drug classes. CONCLUSIONS: Although 2-year therapy and class
      persistence were low for new users of antihypertensive drugs, improvements have
      occurred over the past decade. Our data highlight subgroups to target for future
      persistence improvement interventions.

PMID- 24882538
TI  - Comparison of cardiovascular risk assessment algorithms to determine eligibility
      for statin therapy: implications for practice in Canada.
AB  - BACKGROUND: New lipid management guidelines in the United States have created
      controversy regarding risk assessment using the new Pooled Cohort Equations (PCE)
      which might overestimate cardiovascular risk and identify an excessive number of
      patients as new candidates for statin therapy. METHODS: We compared the
      Framingham Risk Score (FRS) used in Canada with PCE, the FRS version used in
      Adult Treatment Panel III (ATP III), Reynolds Risk Score (RRS), and Systematic
      Coronary Risk Evaluation (SCORE) using patient profile simulation of 10 cohorts
      of 100,000 each (total n = 1,000,000 for each comparison). Patients with
      diabetes, established cardiovascular disease, or family history of premature
      cardiovascular disease were not considered, mimicking uncomplicated primary
      prevention. Analyses were performed separately for men and women and for black
      individuals when feasible. RESULTS: SCORE (high-risk version) was most concordant
      with FRS in men, whereas PCE was most concordant in black women. Compared with
      FRS, all other algorithms except SCORE (high-risk version) identified more
      simulations as low risk. Reclassification from low FRS to a higher risk was not
      seen using RRS or ATP III and seen in < 5% of simulations using PCE, affecting
      predominantly black subject simulations. CONCLUSIONS: Choice of risk calculator
      leads to systematic differences in risk categorization that can influence
      eligibility for lipid-lowering therapy. Compared with FRS, an isolated switch to
      PCE, RRS, or ATP III is unlikely to lead to substantial reclassification from low
      to higher risk categories in Canada.

PMID- 24882537
TI  - Primary care physician visits by patients with incident hypertension.
AB  - BACKGROUND: Access to a primary care physician (PCP) improves health outcomes
      among patients with hypertension. The study objective was to compare PCP use
      among patients with incident hypertension with and without comorbidities.
      METHODS: Hypertensive patients newly diagnosed between April 1, 1998 and March
      31, 2009 were identified using Alberta administrative databases. Three
      comorbidity subgroups were defined: (1) none, (2) vascular risk related, and (3)
      unrelated. The number of PCP visits was calculated using zero-inflation Poisson
      regression, with time trends compared using the chi(2) test. A Cox model was used
      to assess the association between PCP use and clinical outcomes. RESULTS: Of
      456,263 newly diagnosed hypertensive patients (mean age, 57.6 years; 50.6% men;
      62.5% no comorbidity), 88% had seen a PCP in the year before diagnosis, and 94%
      had seen a PCP in the year after being diagnosed. Compared with before diagnosis,
      the mean number of PCP visits increased after diagnosis (none, 3.95 vs 6.15;
      vascular risk related, 6.45 vs 7.99; and unrelated, 6.76 vs 8.24). Over the study
      period, the frequency of PCP visits before diagnosis was constant, and there was
      a statistically significant decline in the adjusted mean number of visits after
      diagnosis. Those with higher PCP use were less likely to die but more likely to
      be hospitalized regardless of comorbidity. CONCLUSIONS: The frequency of PCP
      visits was high before and after diagnosis. Increased PCP use was associated with
      a lower risk of death; however, it does increase the costs of caring for patients
      with hypertension. Therefore, future studies are necessary to determine the
      optimal level required to achieve cost-effective use of PCP resources.

PMID- 24882539
TI  - Risk stratification and selection for statin therapy: going beyond Framingham.
AB  - Decisions for statin therapy in the primary prevention of atherosclerotic
      cardiovascular disease are generally made using the 10-year Framingham Risk Score
      (FRS). Even when a family history of premature cardiovascular disease is taken
      into account, there is often ambiguity about the need for statin therapy for
      patients with a 10-year FRS of 5%-19% and low-density lipoprotein cholesterol
      <3.5 mmol/L. Current Canadian dyslipidemia guidelines recommend consideration of
      a diversity of other factors, including biochemical measurements and imaging
      studies to help determine whether the calculated FRS might be misleadingly low
      and whether statin therapy might, therefore, be prudent. However, efficient use
      of the plethora of secondary factors makes this decision process itself
      potentially ambiguous. This brief summary provides a practical approach for using
      clinical information, basic biochemical tests, and more specialized tests, such
      as carotid ultrasound and coronary artery calcium scoring, to identify groups of
      patients at greater risk for atherosclerotic cardiovascular disease than
      suggested by the FRS. 

PMID- 24882540
TI  - A practical approach to investigation of syncope.
AB  - Syncope is caused by cerebral hypoperfusion. Most fainting is simply vasovagal
      syncope and the challenge lies in identifying the few patients who have
      potentially life-threatening causes of syncope. Syncope patients constitute 1%-2%
      of emergency department visits and approximately 30%-50% are admitted to
      hospital. The known causes are vasovagal syncope (50%), and orthostatic
      hypotension and cardiac syncope (7% each). Structural heart disease is noted in
      3%. The 30-day mortality is only 0.7%, and the 30-day adverse outcome is 4.5%.
      Risk stratification and diagnosis are important. High-risk patients might have a
      fatal cause, and low-risk patients do not. Risk markers include syncope while
      supine or with marked exertion, without a prodrome, with structural heart disease
      or heart failure, with a family history of sudden death, and with an abnormal
      electrocardiographic findings. Ischemic heart disease and hypotension are also
      risk factors. The history captures the preceding situation or activity, prodromal
      symptoms, and symptoms after syncope. Very simple diagnostic scores exist to
      help. Investigations beyond an electrocardiogram are not usually needed, and aim
      to: (1) assess whether a structural substrate exists; (2) capture risk factor
      data, assuming it is related to the syncope; (3) capture data during clinical
      syncope; and (4) induce syncope under controlled conditions. The most commonly
      used tests are implantable loop recorders, which establish a diagnosis in 30%-40%
      of patients over 2-3 years; and tilt table testing. Neither are needed most of
      the time. A good history provides more useful and more accurate information in
      most patients. 

PMID- 24882541
TI  - Whom should I refer in 2014 for cardiac resynchronization?
AB  - Heart failure continues to be a significant source of morbidity and mortality
      amongst Canadians. Many patients remain symptomatic despite guideline-directed
      medical therapy. For drug-refractory patients with dyssynchronous systolic heart
      failure, cardiac resynchronization therapy (CRT) has reliably reduced heart
      failure hospitalizations and related deaths. Unfortunately, despite significant
      advancements in technology and our understanding of its clinical effect, the CRT
      nonresponder rate remains approximately 30%. Great efforts have been invested
      into identifying clinical predictors of CRT response. Left bundle branch block
      conduction delay and wider QRS (> 150 ms) have consistently been associated with
      clinical response to CRT, earning them the strongest recommendations in the
      revised guidelines in Canada and across the world. Due in large part to the
      benefit observed in the Resynchronization-Defibrillation for Ambulatory Heart
      Failure Trial (RAFT) trial, patients with mild heart failure symptoms (New York
      Heart Association class II) are now also candidates for resynchronization
      therapy. Patients with atrial fibrillation, non-left bundle branch block
      conduction patterns, and chronic right ventricular pacing have historically been
      associated with poor response. However, these populations remain grossly
      underrepresented in the large trials. In the absence of more data, these patients
      continue to receive weaker recommendations for CRT in the guidelines. 

PMID- 24882542
TI  - An unusual case of cardiogenic shock: common cause from uncommon etiology.
AB  - Mechanical complications of an acute coronary syndrome can lead to hemodynamic
      instability out of proportion to the degree of left ventricular dysfunction. We
      present the case of a patient with cardiogenic shock secondary to severe mitral
      regurgitation in the setting of an acutely occluded obtuse marginal artery.
      Echocardiography and pathologic findings revealed an uncommon cause of
      anterolateral papillary muscle rupture. Using the unique features of this case,
      we present a clinical self-assessment exercise highlighting the challenges
      involved in the management of this type of patient. 

PMID- 24882543
TI  - Preparing today's cardiovascular trainees to meet the challenges of tomorrow:
      team research and interdisciplinary training.
AB  - There is a growing focus on interdisciplinary team approaches in science and
      public health research, including cardiology. This trend is apparent in a large
      body of team publications and the strong interest from the funding agencies to
      support interdisciplinary research. Despite this increased emphasis on the
      importance and roles of teams, schools fail to better prepare their students and
      trainees with skills that allow them to work in or lead teams. In this article,
      we discuss the strengths and weaknesses of different team models and highlight
      the training program implemented by the Alberta Heart Failure Etiology and
      Analysis Research Team (HEART), which involves 24 scientists/mentors across the
      research and health care spectrum focused on understanding heart failure with
      preserved ejection fraction. 

PMID- 24882544
TI  - SGK1 is involved in cardioprotection of urocortin-1 against hypoxia/reoxygenation
      in cardiomyocytes.
AB  - BACKGROUND: Urocortin-1 (UCN1) exerts protective effects on hypoxia/reoxygenation
      injury in the heart. Serum- and glucocorticoid- responsive kinase-1 (SGK1), a
      serine-threonine kinase, has been shown to be crucial for cardiomyocyte survival.
      The purpose of the present study was to investigate whether SGK1 is involved in
      UCN1-induced cardioprotection. METHODS: Cardiomyocytes were obtained from
      neonatal rats and used as a model to investigate UCN1 regulation of SGK1.
      Specific small interfering RNA targeting SGK1 was used to knock down SGK1
      expression. The messenger RNA (mRNA) level of SGK1 was measured using
      quantitative real time reverse transcription polymerase chain reaction, and the
      protein levels of SGK1 and phosphorylated SGK1 were determined using Western blot
      analysis. RESULTS: SGK1 knockdown attenuated the protective effects of UCN1
      against hypoxia/reoxygenation injury in cardiomyocytes. Treatment of
      cardiomyocytes with UCN1 stimulated SGK1 mRNA and protein expression and time
      dependently increased phosphorylated SGK1 level. These effects were completely
      reversed with corticotrophin-releasing hormone receptor type 2 antagonist.
      Adenylate cyclase and protein kinase A inhibitors abolished the stimulatory
      effect of UCN1 on SGK1 expression. SGK1 phosphorylation induced by UCN1 was
      blocked by phosphorinositide-3-kinase inhibitor. CONCLUSIONS: SGK1 is involved in
      the cardioprotective effects of UCN1 in cardiomyocytes. UCN1 stimulates SGK1
      phosphorylation via the phosphorinositide-3-kinase signalling pathway and it
      induces SGK1 expression via the adenylate cyclase/protein kinase A pathway.

PMID- 24882545
TI  - Treatment optimization of aortocoronary dissection as a complication after heart
      catheterization using coronary computerized tomographic angiography.
AB  - We present the case of a 71-year-old patient with a chronic total occlusion of
      the right coronary artery (RCA) resulting in a retrograde aortic dissection as a
      complication of coronary intervention. Acute therapy consisted of coronary stent
      implantation into the proximal RCA to cover the dissection's entry. One day
      after, computed tomography-guided angiography revealed a progression of the
      intramural aortic hematoma with a residual dissection at the RCA ostium.
      Recurrent coronary angiography was performed to implant another stent covering
      the entry. Imaging at follow-up demonstrated complete coverage of the Dunning
      dissection and regression of the intramural aortic hematoma. 

PMID- 24882546
TI  - Pulsatile chest wall mass complicating myocardial infarction: assessment by two
      dimensional, three-dimensional, and contrast echocardiography.

PMID- 24882548
TI  - Infected marantic endocarditis with leukemoid reaction.

PMID- 24882547
TI  - Ventricular sympathetic innervation in patients with transposition of the great
      arteries after arterial switch operation and Rastelli procedure: impact of
      arterial dissection and coronary reimplantation.
AB  - BACKGROUND: Coronary flow reserve (CFR) is reduced in patients with transposition
      of the great arteries (TGA) after the arterial switch operation (ASO). Dissection
      of the great arteries and coronary reimplantation may result in sympathetic
      denervation, with a negative effect on myocardial perfusion. METHODS AND RESULTS:
      18 patients with TGA participated in the study; 9 had ASO (20.8+/-5.8 years).
      Controls were 9 patients after Rastelli procedure (22.1+/-6.8 years). Sympathetic
      innervation was measured by positron emission tomography using(11)C epinephrine
      (EPI). Left ventricular EPI-retention ranged from 6.1% to 15.9%/min. Patients
      undergoing more than 1 operation had significantly reduced EPI-retention
      (P<0.001). EPI-retention and time interval after surgery correlated significantly
      (r=0.81, P<0.001) and was higher in patients undergoing surgery at an earlier age
      (P<0.001). No significant difference could be found between patients after ASO or
      Rastelli repair. Aortic cross-clamp time inversely correlated with EPI-retention
      (r=-0.72; P<0.001). CONCLUSIONS: The ASO procedure had a negative effect on
      sympathetic innervation of the myocardium, but because of reinnervation
      myocardial perfusion is not essentially altered by this mechanism. Heart surgery
      and prolonged aortic cross-clamp time have a negative effect on the
      norepinephrine content of cardiac sympathetic nerve terminals. Parameters such as
      ventricular performance and cardiopulmonary exercise capacity were unaffected by
      the degree of EPI-retention.

PMID- 24882549
TI  - DNA methylation of human telomerase reverse transcriptase associated with
      leukocyte telomere length shortening in hyperhomocysteinemia-type hypertension in
      humans and in a rat model.
AB  - BACKGROUND: Elevated homocysteine (Hcy) levels might play a role in the
      development of essential hypertension (EH). Telomere dynamics provide valuable
      insight into the pathogenesis of age-related diseases. The contribution of Hcy to
      leukocyte telomere length (LTL) shortening in EH and the underlying mechanism was
      examined. METHODS AND RESULTS: LTL (ratio of the copy number of telomere [T]
      repeats to that of a single [S] gene, T/S ratio) was inversely associated with
      age in patients with EH (n=258) and healthy controls (n=137), but significantly
      decreased with the Hcy level only in patients with hypertension after adjustment
      for age and sex. Age, hypertension and levels of Hcy and low-density lipoprotein
      combined contributed to LTL shortening; an increased serum folate level could
      reverse the Hcy effect seen on multivariate regression analysis. In addition,
      qPCR and methylation-specific PCR assay revealed that LTL shortening and mRNA
      expression and the methylation ratio of human telomerase reverse transcriptase
      (hTERT) were lower in patients with EH than in controls, and gradually decreased
      with increasing Hcy level, but not with blood pressure, in EH patients
      (Ptrend<0.0001, 0.004 and 0.012, respectively). Furthermore,
      Hyperhomocysteinemia, but not hypertension, promoted telomerase reverse
      transcriptase DNA hypomethylation and reduced mRNA levels, which contributed to
      shortened LTL in the hypertension rat model. CONCLUSIONS: Elevated Hcy but not
      hypertension was related to hTERT DNA hypomethylation and reduced mRNA level,
      thus contributing to the shortening of LTL hypertension.

PMID- 24882552
TI  - Daclatasvir for the treatment of hepatitis C virus infection.
AB  - Daclatasvir was pivotal to the trial that established proof-of-concept that an
      interferon-free regimen could induce a sustained virologic response in patients
      with chronic HCV infection. This NS5A inhibitor is not currently licensed for the
      treatment of HCV, but has shown promising efficacy and minimal side-effects in
      clinical trials to date, where it has been tested in combination with a variety
      of different HCV therapies. An all-oral, interferon-free curative combination
      therapy for HCV is now tantalizingly close to becoming part of routine clinical
      practice, with multiple highly-efficacious direct-acting antiviral agents
      emerging virtually simultaneously. In this article we will discuss daclatasvir's
      background and review the clinical trials published to date, concluding with our
      predictions regarding its future place in the treatment armamentarium against
      HCV. 

PMID- 24882551
TI  - Pay attention to impulsivity: modelling low attentive and high impulsive subtypes
      of adult ADHD in the 5-choice continuous performance task (5C-CPT) in female
      rats.
AB  - Varying levels of attention and impulsivity deficits are core features of the
      three subtypes of adult attention deficit-hyperactivity disorder (ADHD). To date,
      little is known about the neurobiological correlates of these subtypes.
      Development of a translational animal model is essential to improve our
      understanding and improve therapeutic strategies. The 5-choice continuous
      performance task (5C-CPT) in rats can be used to examine different forms of
      attention and impulsivity. Adult rats were trained to pre-set 5C-CPT criterion
      and subsequently separated into subgroups according to baseline levels of
      sustained attention, vigilance, premature responding and response disinhibition
      in the 5C-CPT. The behavioural subgroups were selected to represent the different
      subtypes of adult ADHD. Consequently, effects of the clinically used
      pharmacotherapies (methylphenidate and atomoxetine) were assessed in the
      different subgroups. Four subgroups were identified: low-attentive (LA), high
      attentive (HA), high-impulsive (HI) and low-impulsive (LI). Methylphenidate and
      atomoxetine produced differential effects in the subgroups. Methylphenidate
      increased sustained attention and vigilance in LA animals, and reduced premature
      responding in HI animals. Atomoxetine also improved sustained attention and
      vigilance in LA animals, and reduced response disinhibition and premature
      responding in HI animals. This is the first study using adult rats to demonstrate
      the translational value of the 5C-CPT to select subgroups of rats, which may be
      used to model the subtypes observed in adult ADHD. Our findings suggest that this
      as an important paradigm to increase our understanding of the neurobiological
      underpinnings of adult ADHD-subtypes and their response to pharmacotherapy. 

PMID- 24882553
TI  - One-week practice effects in older adults: tools for assessing cognitive change.
AB  - Although neuropsychologists are frequently asked to evaluate cognitive change in
      a patient, this can be a complex determination. Using data from 167 non-demented
      older adults tested twice across one week, the current study sought to provide a
      variety of reliable change indices for a brief battery of commonly used
      neuropsychological measures. Statistically significant improvements were observed
      on seven of nine scores examined over this short retest interval, with the
      largest changes occurring on memory measures. Information is provided on simple
      discrepancy scores, standard deviation index, reliable change index (with and
      without correcting for practice effects), and standardized regression based
      change formulae for each cognitive score. Even though a one-week retesting
      interval is a less typical clinical scenario, these results may give clinicians
      and researchers more options for assessing short-term change in a variety of
      settings.

PMID- 24882554
TI  - A phase II trial of sunitinib in women with metastatic or recurrent endometrial
      carcinoma: a study of the Princess Margaret, Chicago and California Consortia.
AB  - OBJECTIVE: Treatment options remain limited for women with relapsed/metastatic
      endometrial cancer (EC). Angiogenesis is one of the major components of tumor
      progression and thus an attractive target. The aim of this phase II trial was to
      assess the efficacy and tolerability of sunitinib, an oral multitargeted receptor
      tyrosine-kinase inhibitor with antiangiogenic and antitumor activity in the
      treatment of recurrent EC. METHODS: We performed a multicenter, single arm, two
      stage phase II study of sunitinib, 50mg daily administered on a 4 weeks on-2
      weeks off schedule. Eligibility criteria included recurrent/metastatic EC or
      carcinosarcoma with no more than one prior line of chemotherapy. The primary
      endpoint was objective response rate. RESULTS: 34 women were enrolled; 33
      received at least one dose of sunitinib and were included in the analyses. Six
      women (18.1%) had a partial response and six additional women (18.1%) stable
      disease. In total, ten patients (30.3%) had disease control for at least 6 months
      and of these, seven were controlled for more than one year. Median progression
      free and overall survival times were 3 months and 19.4 months, respectively.
      Adverse events related to treatment were frequent. At least one grade 3 toxicity
      occurred in 30 patients and dose reductions were required in 17 patients (52%).
      The most common grade 3 toxicities were fatigue, hypertension, palmar-plantar
      erythrodysesthesia, diarrhea and hematologic. CONCLUSION: Sunitinib therapy
      showed promising activity in women with recurrent EC. Toxicity was seen
      frequently but was manageable. Anti-angiogenic agents warrant further
      investigation in EC to define which patients will derive the greatest benefit.

PMID- 24882555
TI  - A comparison of colorimetric versus fluorometric sentinel lymph node mapping
      during robotic surgery for endometrial cancer.
AB  - OBJECTIVE: The study objective was to compare the ability to detect sentinel
      lymph nodes (SLNs) in women with endometrial cancer (EC) or complex atypical
      hyperplasia (CAH) using fluorometric imaging with indocyanine green (ICG) versus
      colorimetric imaging with isosulfan blue (ISB). METHODS: Women underwent SLN
      mapping, with either ISB or ICG, during robotic-assisted total laparoscopic
      hysterectomy (RA-TLH) from September 2012 to March 2014. SLNs were submitted for
      permanent pathologic analysis. Completion lymphadenectomy and ultrastaging were
      performed according to institutional protocols. RESULTS: RA-TLH and SLN mapping
      was performed in 71 women; 64 had EC (64) and 7 had CAH. Age, body mass index
      (BMI), stage and tumor characteristics were similar in the ICG versus the ISB
      cohorts. Overall, SLNs were identified bilaterally (62.0%), unilaterally (21.1%),
      or neither (16.9%), and in 103 of 142 hemi-pelvises (72.5%). The mean number of
      SLNs retrieved per hemipelvis was 2.23(SD 1.7). SLNs were identified in the
      hypogastric (76.8%), external iliac (14.2%), common iliac (4.5%) and paraaortic
      (4.5%) regions. ICG mapped bilaterally in 78.9% of women compared with 42.4% of
      those injected with ISB (p=0.02). Five women (7%) had positive lymph nodes, all
      identified by the SLN protocol (false negative rate: 0%). On multivariate
      analysis, BMI was negatively correlated with bilateral mapping success (p=0.02).
      When stratified by dye type, the association with BMI was only significant for
      ISB (p=0.03). CONCLUSIONS: Fluorescence imaging with ICG may be superior to
      colorimetric imaging with ISB in women undergoing SLN mapping for endometrial
      cancer. SLN mapping success is negatively associated with increasing patient BMI
      only when ISB is used.

PMID- 24882556
TI  - Maternal and postnatal dietary probiotic supplementation enhances splenic
      regulatory T helper cell population and reduces peanut allergen-induced
      hypersensitivity responses in mice.
AB  - Neonatal to early childhood is the critical period for establishing a balance of
      T helper 1 (Th1) versus T helper 2 (Th2) cellular immunity within the gut, which
      is strongly influenced by the source and establishment of gut microflora.
      Probiotic administration has been shown to attenuate Th2-biased cellular immunity
      and predisposition to food allergies. To test this hypothesis we provided ad
      libitum a probiotic-supplemented (Primalac 454 Feed Grade Microbials) or control
      diet to lactating dams with suckling pups and weaned pups until 10 weeks of age.
      Weaned mice were sensitized/challenged with peanut extract, saline or adjuvant at
      6, 8 and 10 weeks of age. At 3, 6, 8 and 10 weeks, fecal samples were collected
      for microbial analysis, while blood samples were analyzed for total plasma IgE
      levels. At termination (10 weeks of age), splenic T lymphocyte population
      subtypes were determined using FACS analysis and Th1/Th2/Th17 gene expression by
      PCR array. Mice given the probiotic-supplemented diet had significantly enhanced
      probiotic fecal counts compared to controls at 3, 6, 8 and 10 weeks. Moreover,
      mice fed the probiotic-supplemented diet had enhanced splenic naturally occurring
      T regulatory cell populations, and reduced splenic gene expression of allergic
      mediator IL-13 compared to controls. These results provide evidence that early
      probiotic supplementation may provide host protection to hypersensitivity
      reactions to food allergens by attenuating food allergen inflammatory responses.

PMID- 24882557
TI  - Diminished ovarian reserve is the predominant risk factor for gonadotropin
      releasing hormone antagonist failure resulting in breakthrough luteinizing
      hormone surges in in vitro fertilization cycles.
AB  - OBJECTIVE: To identify risk factors for breakthrough LH surge despite GnRH
      antagonist (GnRH-ant) suppression in IVF cycles. DESIGN: Case-control study.
      SETTING: Academic medical center. PATIENT(S): All patients undergoing IVF from
      August 2004 through July 2012 in whom GnRH-ant pituitary suppression (0.25 mg/d)
      was used in a flexible protocol. INTERVENTION(S): GnRH-ant-based IVF. MAIN
      OUTCOME MEASURE(S): Breakthrough LH surges as evidenced by an increase in LH
      (minimum 2.5-fold increase from baseline above a threshold of 17 mIU/mL)
      associated with a decrease in E2, and free fluid on ultrasound. RESULT(S):
      Breakthrough LH surges despite GnRH-ant administration occurred in 37 (0.34%) of
      the 10,809 antagonist cycles during the study period. Compared with all patients
      remaining suppressed, patients with breakthrough surges were significantly older
      and had significantly increased FSH and decreased antral follicle counts.
      Compared with age-matched controls (allocation ratio, 1:50), significant
      differences in ovarian reserve remained evident. CONCLUSION(S): The occurrence of
      a breakthrough LH surge despite GnRH-ant treatment is a reassuringly rare event.
      However, patients with diminished ovarian reserve are at risk for this outcome
      despite GnRH-ant down-regulation. Further studies are needed to determine whether
      these patients can be prospectively identified and whether they may benefit from
      higher doses of GnRH-ant.

PMID- 24882558
TI  - Proteomic identification of target proteins in normal but nonfertilizing sperm.
AB  - OBJECTIVE: To identify the male molecular causes of failures of IVF (with a
      deficient binding of spermatozoa to the zona pellucida, without any obvious
      oocyte anomaly), which are undetected by classical sperm analysis. DESIGN: Case
      control prospective study. SETTING: University hospital. PATIENT(S): Proteomic
      profiles of spermatozoa in patients with a complete failure of fertilization and
      no spermatozoa bound to the zona pellucida were compared with those of controls
      (men with normal fertilization and cleavage rates after classical IVF for tubal
      indication). INTERVENTION(S): All samples were analyzed by two-dimensional
      fluorescence difference gel electrophoresis (2D-DIGE) after being divided into
      three fractions according to their isoelectric point. MAIN OUTCOME MEASURE(S):
      Differentially expressed proteins between infertile men and controls were
      identified by mass spectrometry. RESULT(S): Seventeen proteins differentially
      expressed between cases and controls were found. Twelve of these proteins were
      identified by mass spectrometry, and two may influence gametes interaction:
      laminin receptor LR67 and L-xylulose reductase (P34H). CONCLUSION(S): This study
      shows that 2D-DIGE might be useful in finding potential targets for diagnosis and
      prognosis of idiopathic infertility in IVF.

PMID- 24882561
TI  - Chamber-confined silicon-carbon nanofiber composites for prolonged cycling life
      of Li-ion batteries.
AB  - Silicon is a promising high capacity (4200 mA h g(-1)) anode material for lithium
      ion batteries but the significant volume change (over 300%) of silicon during
      lithiation/delithiation remains a challenge in terms of silicon pulverization and
      solid-electrolyte-interphase (SEI) accumulation in the silicon composite
      electrode. To alleviate the volumetric change of silicon, we built a flexible and
      self-supporting carbon-enhanced carbon nanofiber (CNF) structure with vacant
      chamber to encapsulate Si nanoparticles (vacant Si@CNF@C). This composite was
      tested directly without any polymer and current collector. The confined vacant
      chamber allowed the increasing volume of silicon and SEI accumulates to be well
      retained for a long cycle life. This chamber-confined silicon-carbon nanofiber
      composite exhibited an improved performance in terms of good cycling performance
      (620 mA h g(-1)), high coulombic efficiency (99%), and good capacity retention
      (80%) after 200 cycles. This self-supported silicon-carbon nanofiber structure
      showed high flexibility and good electrochemical performance for the potential as
      flexible electrode for lithium-ion batteries. 

PMID- 24882560
TI  - A literature review of learning collaboratives in mental health care: used but
      untested.
AB  - OBJECTIVE: Policy makers have increasingly turned to learning collaboratives
      (LCs) as a strategy for improving usual care through the dissemination of
      evidence-based practices. The purpose of this review was to characterize the
      state of the evidence for use of LCs in mental health care. METHODS: A systematic
      search of major academic databases for peer-reviewed articles on LCs in mental
      health care generated 421 unique articles across a range of disciplines; 28
      mental health articles were selected for full-text review, and 20 articles
      representing 16 distinct studies met criteria for final inclusion. Articles were
      coded to identify the LC components reported, the focus of the research, and key
      findings. RESULTS: Most of the articles included assessments of provider- or
      patient-level variables at baseline and post-LC. Only one study included a
      comparison condition. LC targets ranged widely, from use of a depression
      screening tool to implementation of evidence-based treatments. Fourteen
      crosscutting LC components (for example, in-person learning sessions, phone
      meetings, data reporting, leadership involvement, and training in quality
      improvement methods) were identified. The LCs reviewed reported including, on
      average, seven components, most commonly in-person learning sessions, plan-do
      study-act cycles, multidisciplinary quality improvement teams, and data
      collection for quality improvement. CONCLUSIONS: LCs are being used widely in
      mental health care, although there is minimal evidence of their effectiveness and
      unclear reporting in regard to specific components. Rigorous observational and
      controlled research studies on the impact of LCs on targeted provider- and
      patient-level outcomes are greatly needed.

PMID- 24882562
TI  - Therapeutic benefits of H2S in Alzheimer's disease.
AB  - Hydrogen sulfide (H2S), an endogenously generated gaseous mediator, has been
      discovered to regulate a series of physiological and pathological processes in
      mammalian systems. In recent decades scientific interest has grown in the
      physiological and pathological implications of H2S, specifically its role in the
      central nervous system (CNS). H2S can work in the CNS as a neuromodulator to
      promote long-term potentiation and regulate intracellular calcium concentration
      and pH level in brain cells. H2S may protect the nervous system from oxidative
      stress, apoptosis, or degeneration. The aim of this review is to present the
      current understanding of H2S as a potential agent for the treatment of
      Alzheimer's disease (AD). Dysregulation of H2S homeostasis is implicated in the
      pathological processes of AD. Substantial evidence from both in vivo and in vitro
      studies shows that H2S prevents neuronal impairment and attenuates cognitive
      dysfunction in the experimental model of AD. The mechanisms underlying the
      protective role of H2S in AD involve its antioxidant, anti-apoptotic, and anti
      inflammatory effects. We conclude that H2S has potential therapeutic value for
      the treatment of AD. 

PMID- 24882563
TI  - Modulation of mind: therapeutic neuromodulation for cognitive disability.
AB  - Neuromodulation using deep brain stimulation (DBS) has become an established
      therapy for the treatment of certain disorders such as Parkinson's disease and
      tremors. Recent advances in surgical and imaging techniques further decrease the
      surgical risk associated with these procedures. Symptoms such as tremor,
      bradykinesia, rigidity and gait disturbances can be significantly controlled with
      DBS. This results in an opportunity to decrease anti-parkinsonism medications,
      and their dyskinetic side-effects. Following the success of DBS in the management
      of movement disorders, the role of this therapy is being extensively studied in
      more complex disorders that involve cognition and behavior. The inherent
      complexity in cognitive circuitry makes neuromodulation using DBS more difficult
      than in movement disorders. The goal of DBS surgery in these diseases is not only
      to slow the cognitive decline, but also restoration of function and ultimately
      improvement in the quality of life. DBS as a treatment for patients with advanced
      dementia holds significant promise in delaying or reversing the progressive
      cognitive decline by enhancing connectivity in the memory networks. In
      appropriately selected patients this potentially reversible surgical therapy can
      lead to a significant improvement in the quality of life and reduce the burden on
      patients, families and the healthcare system. This review focuses on the recent
      and future studies involving neuromodulation for cognitive disorders such as
      Alzheimer's disease and Huntington's disease. 

PMID- 24882564
TI  - Altered social interactions in male juvenile cynomolgus monkeys prenatally
      exposed to bisphenol A.
AB  - Bisphenol A (BPA) is a widespread environmental contaminant, and humans are
      routinely exposed to BPA. We investigated whether prenatal exposure to BPA
      influences behavioral development in juvenile cynomolgus monkeys (Macaca
      fascicularis). Pregnant cynomolgus monkeys were implanted with subcutaneous pumps
      and exposed to 10MUg/kg/day BPA or vehicle (control) from gestational day 20 to
      132. Both BPA-exposed and control juvenile monkeys (aged 1-2years) were assessed
      using the peer-encounter test that was conducted to evaluate behaviors in social
      interaction with a same-sex, same-treatment peer. In the encounter test, prenatal
      BPA exposure significantly reduced environmental exploration and presenting, a
      gesture related to sexual reproduction, and increased visual exploration, but
      only in males; furthermore, it significantly reduced the typical sexual
      dimorphism of the aforementioned behaviors normally observed between male and
      female juvenile cynomolgus monkeys. This study demonstrates that prenatal BPA
      exposure affects behavioral development during adolescence and results in the
      demasculinization of key sexually dimorphic behaviors in male juvenile monkeys. 

PMID- 24882565
TI  - Note of clarification.

PMID- 24882567
TI  - Psilocybin-Induced Decrease in Amygdala Reactivity Correlates with Enhanced
      Positive Mood in Healthy Volunteers.
AB  - BACKGROUND: The amygdala is a key structure in serotonergic emotion-processing
      circuits. In healthy volunteers, acute administration of the serotonin 1A/2A/2C
      receptor agonist psilocybin reduces neural responses to negative stimuli and
      induces mood changes toward positive states. However, it is little-known whether
      psilocybin reduces amygdala reactivity to negative stimuli and whether any change
      in amygdala reactivity is related to mood change. METHODS: This study assessed
      the effects of acute administration of the hallucinogen psilocybin (.16 mg/kg)
      versus placebo on amygdala reactivity to negative stimuli in 25 healthy
      volunteers using blood oxygen level-dependent functional magnetic resonance
      imaging. Mood changes were assessed using the Positive and Negative Affect
      Schedule and the state portion of the State-Trait Anxiety Inventory. A double
      blind, randomized, cross-over design was used with volunteers counterbalanced to
      receive psilocybin and placebo in two separate sessions at least 14 days apart.
      RESULTS: Amygdala reactivity to negative and neutral stimuli was lower after
      psilocybin administration than after placebo administration. The psilocybin
      induced attenuation of right amygdala reactivity in response to negative stimuli
      was related to the psilocybin-induced increase in positive mood state.
      CONCLUSIONS: These results demonstrate that acute treatment with psilocybin
      decreased amygdala reactivity during emotion processing and that this was
      associated with an increase of positive mood in healthy volunteers. These
      findings may be relevant to the normalization of amygdala hyperactivity and
      negative mood states in patients with major depression.

PMID- 24882566
TI  - Amygdala-prefrontal cortex functional connectivity during threat-induced anxiety
      and goal distraction.
AB  - BACKGROUND: Anxiety produced by environmental threats can impair goal-directed
      processing and is associated with a range of psychiatric disorders, particularly
      when aversive events occur unpredictably. The prefrontal cortex (PFC) is thought
      to implement controls that minimize performance disruptions from threat-induced
      anxiety and goal distraction by modulating activity in regions involved in threat
      detection, such as the amygdala. The inferior frontal gyrus (IFG), orbitofrontal
      cortex (OFC), and ventromedial PFC (vmPFC) have been linked to the regulation of
      anxiety during threat exposure. We developed a paradigm to determine if threat
      induced anxiety would enhance functional connectivity between the amygdala and
      IFG, OFC, and vmPFC. METHODS: Healthy adults performed a computer-gaming style
      task involving capturing prey and evading predators to optimize monetary rewards
      while exposed to the threat of unpredictable shock. Psychophysiological recording
      (n = 26) and functional magnetic resonance imaging scanning (n = 17) were
      collected during the task in separate cohorts. Task-specific changes in
      functional connectivity with the amygdala were examined using psychophysiological
      interaction analysis. RESULTS: Threat exposure resulted in greater arousal
      measured by increased skin conductance but did not influence performance (i.e.,
      monetary losses or rewards). Greater functional connectivity between the right
      amygdala and bilateral IFG, OFC, vmPFC, anterior cingulate cortex, and
      frontopolar cortex was associated with threat exposure. CONCLUSIONS: Exposure to
      unpredictable threat modulates amygdala-PFC functional connectivity that may help
      maintain performance when experiencing anxiety induced by threat. Our paradigm is
      well-suited to explore the neural underpinnings of the anxiety response to
      unpredictable threat in patients with various anxiety disorders.

PMID- 24882569
TI  - Responsible but unprepared: experiences of newly educated nurses in hospital
      care.
AB  - The purpose of this study was to highlight the experience of being newly educated
      nurses working in internal medicine and surgical units. The nurses were asked to
      recount their initial work experiences using a narrative approach. A
      phenomenological hermeneutic method developed for life experience research was
      applied in the analyses. The study participants were surprised by the discrepancy
      between the ideals and the theoretical and practical knowledge gained during
      their nursing education, and the assigned hospital tasks designated as routine
      care. Prominent features of this were a focus on medical diagnostics and
      treatment, task orientation and efficiency. Holistic nursing was not felt to be a
      priority within the unit. This led to frustration and feelings of inadequacy and
      unpreparedness. They also felt that the responsibility was overwhelming. The
      findings described are discussed in the context of related publications. 

PMID- 24882568
TI  - Presynaptic Serotoninergic Regulation of Emotional Processing: A Multimodal Brain
      Imaging Study.
AB  - BACKGROUND: The amygdala is a central node in the brain network that processes
      aversive emotions and is extensively innervated by dorsal raphe nucleus (DRN)
      serotonin (5-hydroxytryptamine [5-HT]) neurons. Alterations in DRN 5-HT1A
      receptor availability cause phenotypes characterized by fearful behavior in
      preclinical models. However, it is unknown whether 5-HT1A receptor availability
      is linked specifically to the processing of aversive emotions in humans or
      whether it modulates connectivity in brain networks involved in emotion
      processing. To answer this question, we investigated the relationship between DRN
      5-HT1A receptor availability and amygdala reactivity to aversive emotion and
      functional connectivity within the amygdala-cortical network. METHODS: We studied
      15 healthy human participants who underwent positron emission tomography scanning
      with [(11)C]CUMI-101, a 5-HT1A partial agonist radioligand, and functional
      magnetic resonance imaging of brain responses during an incidental emotion
      processing task including happy, fearful, and neutral faces. Regional estimates
      of 5-HT1A receptor binding potential (nondisplaceable) were obtained by
      calculating total volumes of distribution for presynaptic DRN and amygdala.
      Connectivity between the amygdala and corticolimbic areas was assessed using
      psychophysiologic interaction analysis with the amygdala as the seed region.
      RESULTS: Analysis of the fear versus neutral contrast revealed a significant
      negative correlation between amygdala response and DRN binding potential
      (nondisplaceable) (r = -.87, p < .001). Availability of DRN 5-HT1A receptors
      positively correlated with amygdala connectivity with middle frontal gyrus,
      anterior cingulate cortex, bilateral precuneus, and left supramarginal gyrus for
      fearful (relative to neutral) faces. CONCLUSIONS: Our data show that DRN 5-HT1A
      receptor availability is linked specifically to the processing of aversive
      emotions in the amygdala and the modulation of amygdala-cortical connectivity.

PMID- 24882570
TI  - Up-regulation of DNAM-1 and NKp30, associated with improvement of NK cells
      activation after long-term culture of mononuclear cells from patients with
      ovarian neoplasia.
AB  - This study aimed at evaluating the functional activation and activating receptors
      expression on resting, short- and long-term NK and NK-like T cells from blood of
      ovarian neoplasia patients. Blood from patients with adnexal benign alterations
      (n = 10) and ovarian cancer (grade I-IV n = 14) were collected after signed
      consent. Effector cells activation was evaluated by the expression of the CD107a
      molecule. Short-term culture was conducted overnight with IL-2 and long-term
      culture for 21 days, by a method designed to expand CD56(+) lymphocytes. Short
      term culture significantly increased NK cells activation compared to resting NK
      cells (p<0.05), however, the long-term procedure supported an even higher
      increase (p<0.001). Resting NK-like T cells showed poor activation, which was not
      altered by the culture procedures. The long-term culture effectively increased
      the expression of the activating receptors on NK and NK-like T cells, either by
      increasing the number of cells expressing a given receptor and/or by up
      regulating their expression intensity. As a conclusion, the long-term culture
      system employed, resulted in a high number of functional NK cells. The culture
      system was particularly efficient on the up-regulation of NKp30 and DNAM-1
      receptors on NK cells.

PMID- 24882571
TI  - Attenuated TLRs in middle ear mucosa contributes to susceptibility of chronic
      suppurative otitis media.
AB  - The variability in the recovery of otitis media (OM) is not well understood.
      Recent data have shown a critical role for toll-like receptors (TLRs) in
      inflammatory responses to bacteria. It remains unclear whether TLRs-mediated
      mucosal immunity plays a role in the OM recovery. The etiology, pathological
      profile, expression levels of TLR2, TLR4, TLR5, TLR9 and proinflammatory
      cytokines were measured in human middle-ear mucosae sampled from three subject
      groups: non-OM group, chronic otitis-media (COM) group, and chronic suppurative
      otitis-media (CSOM) group. Of the 72 ears, 86.11% CSOM patients were positive for
      bacteria. The cellular makeup of the middle ear mucosa differs among the three
      groups. Mucosae from the CSOM group presented chronic inflammation or suppurative
      inflammation in the rudimentary stroma, mainly with infiltration of monocytes and
      macrophages. The mRNA and protein levels of TLR2, TLR4, and TLR5 exhibited no
      difference between the non-OM and COM groups but were significantly lower in the
      CSOM group. Conversely, there was no significant difference in the TLR9 level
      among the three groups. Furthermore, proinflammatory cytokines TNF-alpha, IL
      1beta, IFN-gamma, IL-6 were up-regulated in the CSOM group. This study provides
      evidence that the variability in clinical otitis media recovery might be
      associated with the variability in the expression of mucosal TLRs. Reduced TLR
      levels in the middle-ear mucosa might cause weak host response to bacteria,
      persistent inflammation and susceptibility to CSOM. 

PMID- 24882572
TI  - Myeloperoxidase gene polymorphism predicts fibrosis severity in women with
      hepatitis C.
AB  - Oxidative stress plays an important role on liver fibrosis progression in the
      course of hepatitis C virus (HCV) infection. Myeloperoxidase (MPO) is an enzyme
      released by neutrophils and macrophages, responsible for generating hypochlorous
      acid and reactive oxygen species (ROS) that may lead to liver injury in HCV
      infection. On the other hand, antioxidant enzymes such as manganese superoxide
      dismutase (SOD) controls ROS-mediated damage. The aim of the present study was to
      investigate the influence of MPO G-463A and SOD2 Ala16Val polymorphisms in the
      severity of liver fibrosis in individuals with chronic HCV infection. The present
      study included 270 patients with chronic HCV recruited from the Gastrohepatology
      Service of the Oswaldo Cruz University Hospital/Liver Institute of Pernambuco
      (Recife, Northeastern Brazil). All patients underwent liver biopsy, which was
      classified according METAVIR score. The SNPs were determined by real-time PCR.
      After multivariate analysis adjustment, the GG genotype of MPO and the presence
      of metabolic syndrome were independently associated with fibrosis severity in
      women (P = 0.025 OR 2.25 CI 1.10-4.59 and P = 0.032 OR 2.32 CI 1.07-5.01,
      respectively). The presence of the GG genotype seems to be a risk factor for
      fibrosis severity in women with HCV.

PMID- 24882573
TI  - Aligning population-based care management with chronic disease complexity.
AB  - BACKGROUND: Risk-stratified care management requires knowledge of the complexity
      of chronic disease and comorbidity, information that is often not readily
      available in the primary care setting. The purpose of this article was to
      describe a population-based approach to risk-stratified care management that
      could be applied in primary care. METHODS: Three populations (Medicaid, Medicare,
      and privately insured) at a regional health plan were divided into risk
      stratified cohorts based on chronic disease and complexity, and utilization was
      compared before and after the implementation of population-specific care
      management teams of nurses. RESULTS: Risk-stratified care management was
      associated with reductions in hospitalization rates in all three populations, but
      the opportunities to avoid admissions were different. CONCLUSIONS: Knowledge of
      population complexity is critical to the development of risk-stratified care
      management in primary care, and a complexity matrix can help nurses identify gaps
      in care and align interventions to cohort and population needs.

PMID- 24882574
TI  - Targeting the oncogenic Met receptor by antibodies and gene therapy.
AB  - The receptor for hepatocyte growth factor (HGF), a tyrosine kinase encoded by the
      Met oncogene, has a crucial role in cancer growth, invasion and metastasis. It is
      a validated therapeutic target for 'personalized' treatment of a number of
      malignancies. Therapeutic tools prompting selective, robust and highly effective
      Met inhibition potentially represent a major step in the battle against cancer.
      Antibodies targeting either Met or its ligand HGF, although challenging,
      demonstrate to be endowed with promising features. Here we briefly review and
      discuss the state of the art in the field.

PMID- 24882575
TI  - RACK1, a versatile hub in cancer.
AB  - RACK1 is a highly conserved intracellular adaptor protein with significant
      homology to Gbeta and was originally identified as the anchoring protein for
      activated protein kinase C. In the past 20 years, the number of binding partners
      and validated cellular functions for RACK1 has increased, which facilitates
      clarification of its involvement in different biological events. In this review,
      we will focus on its role in cancer, summarizing its aberrant expression, pro- or
      anti-oncogenic effects and the underlying mechanisms in various cancers.

PMID- 24882576
TI  - Caspase-2: the reinvented enzyme.
AB  - On the basis of evidences that caspase-2 gene targeting in several generated
      mouse models accelerates tumor formation, this enzyme was recently implicated in
      tumor suppression. The observed function, however, compels other molecular
      perturbations harboring tumorigenic properties. Therefore, the question remains
      as to whether or not caspase-2 can be considered a true tumor suppressor? The
      traditional view of caspase-2 being vital for the apoptotic response to induced
      cell stress in some systems is in line with these findings. Yet, caspase-2 has
      also been associated with other processes which equally might interfere with
      tumorigenic potential, including the oxidative stress response, aging and genome
      surveillance. By different mechanisms, this enzyme has been proposed to function
      as a checkpoint regulator in the cell cycle. Together, these data indicate that
      caspase-2 is a highly versatile factor, a view that is contrasted by the
      alternative explanation where the enzyme harbors a mechanism affecting a discrete
      process, which in turn is functionally connected to other cell systems. In any
      case, it is clear that the general view of caspase-2 as a protein mainly involved
      in apoptotic cell death is shattered. Hence, we wish to discuss the perspectives
      of recent achievements in caspase-2-related research.

PMID- 24882577
TI  - Gene expression profiling identifies FYN as an important molecule in tamoxifen
      resistance and a predictor of early recurrence in patients treated with endocrine
      therapy.
AB  - To elucidate the molecular mechanisms of tamoxifen resistance in breast cancer,
      we performed gene array analyses and identified 366 genes with altered expression
      in four unique tamoxifen-resistant (TamR) cell lines vs the parental tamoxifen
      sensitive MCF-7/S0.5 cell line. Most of these genes were functionally linked to
      cell proliferation, death and control of gene expression, and include FYN, PRKCA,
      ITPR1, DPYD, DACH1, LYN, GBP1 and PRLR. Treatment with FYN-specific small
      interfering RNA or a SRC family kinase inhibitor reduced cell growth of TamR cell
      lines while exerting no significant effect on MCF-7/S0.5 cells. Moreover,
      overexpression of FYN in parental tamoxifen-sensitive MCF-7/S0.5 cells resulted
      in reduced sensitivity to tamoxifen treatment, whereas knockdown of FYN in the
      FYN-overexpressing MCF-7/S0.5 cells restored sensitivity to tamoxifen,
      demonstrating growth- and survival-promoting function of FYN in MCF-7 cells. FYN
      knockdown in TamR cells led to reduced phosphorylation of 14-3-3 and Cdc25A,
      suggesting that FYN, by activation of important cell cycle-associated proteins,
      may overcome the anti-proliferative effects of tamoxifen. Evaluation of the
      subcellular localization of FYN in primary breast tumors from two cohorts of
      endocrine-treated ER+ breast cancer patients, one with advanced disease (N=47)
      and the other with early disease (N=76), showed that in the former, plasma
      membrane-associated FYN expression strongly correlated with longer progression
      free survival (P<0.0002). Similarly, in early breast cancer patients, membrane
      associated expression of FYN in the primary breast tumor was significantly
      associated with increased metastasis-free (P<0.04) and overall (P<0.004) survival
      independent of tumor size, grade or lymph node status. Our results indicate that
      FYN has an important role in tamoxifen resistance, and its subcellular
      localization in breast tumor cells may be an important novel biomarker of
      response to endocrine therapy in breast cancer.

PMID- 24882578
TI  - Receptor-type protein tyrosine phosphatase kappa directly dephosphorylates CD133
      and regulates downstream AKT activation.
AB  - Although CD133 has been considered to be a molecular marker for cancer stem
      cells, its functional roles in tumorigenesis remain unclear. We here examined the
      molecular basis behind CD133-mediated signaling. Knockdown of CD133 resulted in
      the retardation of xenograft tumor growth of colon cancer-derived HT-29 and LoVo
      cells accompanied by hypophosphorylation of AKT, which diminished beta-catenin/T
      cell factor-mediated CD44 expression. As tyrosine residues of CD133 at positions
      828 and 852 were phosphorylated in HT-29 and SW480 cells, we further addressed
      the significance of this phosphorylation in the tumorigenesis of SW480 cells
      expressing mutant CD133, with substitution of these tyrosine residues by
      glutamate (CD133-EE) or phenylalanine (CD133-FF). Forced expression of CD133-EE
      promoted much more aggressive xenograft tumor growth relative to wild-type CD133
      expressing cells accompanied by hyperphosphorylation of AKT; however, CD133-FF
      expression had negligible effects on AKT phosphorylation and xenograft tumor
      formation. Intriguingly, the tyrosine phosphorylation status of CD133 was closely
      linked to the growth of SW480-derived spheroids. Using yeast two-hybrid
      screening, we finally identified receptor-type protein tyrosine phosphatase kappa
      (PTPRK) as a binding partner of CD133. In vitro studies demonstrated that PTPRK
      associates with the carboxyl-terminal region of CD133 through its intracellular
      phosphatase domains and also catalyzes dephosphorylation of CD133 at tyrosine
      828/tyrosine-852. Silencing of PTPRK elevated the tyrosine phosphorylation of
      CD133, whereas forced expression of PTPRK reduced its phosphorylation level
      markedly and abrogated CD133-mediated AKT phosphorylation. Endogenous CD133
      expression was also closely associated with higher AKT phosphorylation in primary
      colon cancer cells, and ectopic expression of CD133 enhanced AKT phosphorylation.
      Furthermore, lower PTPRK expression significantly correlated with the poor
      prognosis of colon cancer patients with high expression of CD133. Thus, our
      present findings strongly indicate that the tyrosine phosphorylation of CD133,
      which is dephosphorylated by PTPRK, regulates AKT signaling and has a critical
      role in colon cancer progression.

PMID- 24882579
TI  - miR-339-5p regulates the p53 tumor-suppressor pathway by targeting MDM2.
AB  - MicroRNAs (miRNAs) regulate many key cancer-relevant pathways and may themselves
      possess oncogenic or tumor-suppressor functions. Consequently, miRNA
      dysregulation has been shown to be a prominent feature in many human cancers. The
      p53 tumor suppressor acts as a negative regulator of cell proliferation in
      response to stress and represents the most commonly lost and mutated gene in
      human cancers. The function of p53 is inhibited by the MDM2 oncoprotein. Using a
      high-throughput screening approach, we identified miR-339-5p as a regulator of
      the p53 pathway. We demonstrate that this regulation occurs via the ability of
      miR-339-5p to target directly the 3'-untranslated region of MDM2 mRNA, reducing
      MDM2 expression and thus promoting p53 function. Consequently, overexpression of
      miR-339-5p positively impacts on p53-governed cellular responses such as
      proliferation arrest and senescence, whereas inhibition of miR-339-5p function
      perturbs the p53 response in cancer cells, allowing an increased proliferation
      rate. In addition, miR-339-5p expression is downregulated in tumors harboring
      wild-type TP53, suggesting that reduction of miR-339-5p level helps to suppress
      the p53 response in p53-competent tumor cells. Furthermore, we show that a
      negative correlation between miR-339-5p and MDM2 expression exists in human
      cancer, implying that the interaction is important for cancer development.

PMID- 24882581
TI  - MicroRNA-885-3p inhibits the growth of HT-29 colon cancer cell xenografts by
      disrupting angiogenesis via targeting BMPR1A and blocking BMP/Smad/Id1 signaling.
AB  - The previous studies in this lab discovered that microRNA-885-3p (miR-885-3p) was
      regulated by a sulfated polysaccharide that bound to bone morphogenetic protein
      receptor, type IA (BMPR1A) to inhibit angiogenesis. However, its specific role
      and its mechanism of action in tumor cells have not been elucidated. We show that
      miR-885-3p markedly suppresses angiogenesis in vitro and in vivo. MiR-885-3p
      inhibits Smad1/5/8 phosphorylation and downregulates DNA-binding protein
      inhibitor ID-1 (Id1), a proangiogenic factor, by targeting BMPR1A, leading to
      impaired angiogenesis. Overexpression or silencing of BMPR1A affects angiogenesis
      in a Smad/Id1-dependent manner. We further show that miR-885-3p impairs the
      growth of HT-29 colon cancer cell xenografts in nude mice by suppressing
      angiogenesis through disruption of BMPR1A and Smad/Id1 signaling. These results
      support a novel role for miR-885-3p in tumor angiogenesis by targeting BMPR1A,
      which regulates a proangiogenic factor, and provide new evidence that targeting
      miRNAs might be an effective therapeutic strategy for improving colon cancer
      treatment.

PMID- 24882580
TI  - Effects of tumor-suppressor lysyl oxidase propeptide on prostate cancer xenograft
      growth and its direct interactions with DNA repair pathways.
AB  - Lysyl oxidase (LOX) is a multifunctional protein required for normal collagen and
      elastin biosynthesis and maturation. In addition, LOX has complex roles in cancer
      in which the lysyl oxidase propeptide (LOX-PP) domain of secreted pro-LOX has
      tumor-suppressor activity, while the active enzyme promotes metastasis. In
      prostate cancer cell lines, recombinant LOX-PP (rLOX-PP) inhibits the growth of
      PC3 cells in vitro by mechanisms that were not characterized, while in DU145
      cells rLOX-PP targeted fibroblast growth factor signaling. Because rLOX-PP can
      enhance effects of a genotoxic chemotherapeutic on breast cancer cell apoptosis,
      we reasoned that rLOX-PP could target DNA repair pathways typically elevated in
      cancer. Here we demonstrate for the first time that rLOX-PP inhibits prostate
      xenograft growth in vivo and that activating phosphorylations of the key DNA
      repair molecules ataxia-telangiectasia mutated (ATM) and checkpoint kinase 2
      (CHK2) are inhibited by rLOX-PP expression in vivo. In addition, in vitro studies
      showed that rLOX-PP inhibits radiation-induced activating phosphorylations of ATM
      and CHK2 and that exogenously added rLOX-PP protein can localize to the nucleus
      in both DU145 and PC3 cells. rLOX-PP pull-down studies resulted in detection of a
      protein complex with the nuclear DNA repair regulator MRE11 in both cell lines,
      and rLOX-PP localized to radiation-induced nuclear DNA repair foci. Finally, rLOX
      PP was shown to sensitize both DU145 and PC3 cells to radiation-induced cell
      death determined in colony-formation assays. These data provide evidence that
      rLOX-PP has a nuclear mechanism of action in which it directly interacts with DNA
      repair proteins to sensitize prostate cancer cells to the effects of ionizing
      radiation.

PMID- 24882582
TI  - Activation of mTOR pathway in myeloid-derived suppressor cells stimulates cancer
      cell proliferation and metastasis in lal(-/-) mice.
AB  - Inflammation critically contributes to cancer metastasis, in which myeloid
      derived suppressor cells (MDSCs) are an important participant. Although MDSCs are
      known to suppress immune surveillance, their roles in directly stimulating cancer
      cell proliferation and metastasis currently remain unclear. Lysosomal acid lipase
      (LAL) deficiency causes systemic expansion and infiltration of MDSCs in multiple
      organs and subsequent inflammation. In the LAL-deficient (lal(-/-)) mouse model,
      melanoma metastasized massively in allogeneic lal(-/-) mice, which was suppressed
      in allogeneic lal(+/+) mice owing to immune rejection. Here we report for the
      first time that MDSCs from lal(-/-) mice directly stimulated B16 melanoma cell in
      vitro proliferation and in vivo growth and metastasis. Cytokines, that is,
      interleukin-1beta and tumor necrosis factor-alpha from MDSCs are required for B16
      melanoma cell proliferation in vitro. Myeloid-specific expression of human LAL
      (hLAL) in lal(-/-) mice rescues these malignant phenotypes in vitro and in vivo.
      The tumor-promoting function of lal(-/-) MDSCs is mediated, at least in part,
      through overactivation of the mammalian target of rapamycin (mTOR) pathway.
      Knockdown of mTOR, Raptor or Rictor in lal(-/-) MDSCs suppressed their
      stimulation on proliferation of cancer cells, including B16 melanoma, Lewis lung
      carcinoma and transgenic mouse prostate cancer-C2 cancer cells. Our results
      indicate that LAL has a critical role in regulating MDSCs' ability to directly
      stimulate cancer cell proliferation and overcome immune rejection of cancer
      metastasis in allogeneic mice through modulation of the mTOR pathway, which
      provides a mechanistic basis for targeting MDSCs to reduce the risk of cancer
      metastasis. Therefore MDSCs possess dual functions to facilitate cancer
      metastasis: suppress immune surveillance and stimulate cancer cell proliferation
      and growth.

PMID- 24882583
TI  - Initial and extended use of femoral versus nonfemoral double-lumen vascular
      catheters and catheter-related infection during continuous renal replacement
      therapy.
AB  - BACKGROUND: The risk of catheter-related infection or bacteremia, with initial
      and extended use of femoral versus nonfemoral sites for double-lumen vascular
      catheters (DLVCs) during continuous renal replacement therapy (CRRT), is unclear.
      STUDY DESIGN: Retrospective observational cohort study. SETTING & PARTICIPANTS:
      Critically ill patients on CRRT in a combined intensive care unit of a tertiary
      institution. FACTOR: Femoral versus nonfemoral venous DLVC placement. OUTCOMES:
      Catheter-related colonization (CRCOL) and bloodstream infection (CRBSI).
      MEASUREMENTS: CRCOL/CRBSI rates expressed per 1,000 catheter-days. RESULTS: We
      studied 458 patients (median age, 65 years; 60% males) and 647 DLVCs. Of 405
      single-site only DLVC users, 82% versus 18% received exclusively 419 femoral
      versus 82 jugular or subclavian DLVCs, respectively. The corresponding DLVC
      indwelling duration was 6+/-4 versus 7+/-5 days (P=0.03). Corresponding CRCOL and
      CRBSI rates (per 1,000 catheter-days) were 9.7 versus 8.8 events (P=0.8) and 1.2
      versus 3.5 events (P=0.3), respectively. Overall, 96 patients with extended CRRT
      received femoral-site insertion first with subsequent site change, including 53
      femoral guidewire exchanges, 53 new femoral venipunctures, and 47 new
      jugular/subclavian sites. CRCOL and CRBSI rates were similar for all such
      approaches (P=0.7 and P=0.9, respectively). On multivariate analysis, CRCOL risk
      was higher in patients older than 65 years and weighing >90kg (ORs of 2.1 and
      2.2, respectively; P<0.05). This association between higher weight and greater
      CRCOL risk was significant for femoral DLVCs, but not for nonfemoral sites. Other
      covariates, including initial or specific DLVC site, guidewire exchange versus
      new venipuncture, and primary versus secondary DLVC placement, did not
      significantly affect CRCOL rates. LIMITATIONS: Nonrandomized retrospective design
      and single-center evaluation. CONCLUSIONS: CRCOL and CRBSI rates in patients on
      CRRT are low and not influenced significantly by initial or serial femoral
      catheterizations with guidewire exchange or new venipuncture. CRCOL risk is
      higher in older and heavier patients, the latter especially so with femoral
      sites.

PMID- 24882584
TI  - Large middle ear schwannoma of the Jacobson's nerve with intracranial extension.
AB  - The patient is a 64-year-old woman who developed a sensation of right ear
      fullness and hearing loss in early November 2010. Physical examination revealed a
      painless reddish granular lesion filling in the right external auditory canal.
      Her right ear was deaf, and no facial palsy was noted. Computed tomography,
      magnetic resonance imaging and positron emission tomography revealed a middle ear
      mass extending to the external auditory canal with intracranial invasion causing
      temporal lobe retraction and inferiorly extending just anterior to the jugular
      bulb as well. A combination of transmastoid and middle cranial fossa approach
      along with anterior rerouting of the facial nerve was employed for a near-total
      removal of the tumor. Based upon the operative findings, it was deemed that the
      tumor could have arisen from the Jacobson's nerve. 

PMID- 24882586
TI  - Vestibular evoked myogenic potentials in children after cochlear implantation.
AB  - OBJECTIVE: The aim of this study was to report the effect of unilateral cochlear
      implantation to vestibular system using vestibular evoked myogenic potentials
      (VEMPs) by air-conduction in a sample of children aged less than 5 years.
      MATERIALS: This study consisted of 10 children (6 boys and 4 girls), who
      underwent cochlear implantation surgery at our clinic, and 8 normal hearing
      children (5 boys and 3 girls) matched for age. The VEMPs were performed before,
      10 days, and 6 months after surgery. Both the implanted and unimplanted ears of
      each child were evaluated, with the cochlear implant both off and on. RESULTS:
      Preoperatively, six (60%) children had abnormal VEMPs responses on both ears. In
      the postoperative sessions, no child showed any VEMPs response on the implanted
      side. The VEMPs were not recorded on the unimplanted side either, except for one
      case. At 6 months, the VEMPs response on the unimplanted side of three children
      became normal when the cochlear implant was on, and in two children with the
      device off. CONCLUSION: In the postoperative 6-month-period, the disappearance of
      VEMPs suggests that the saccule of children can be extensively damaged following
      cochlear implantation. A recovery of VEMPs can take place on the unimplanted
      side, with the cochlear implant both on and off. Despite this saccular injury,
      the absence of clinical signs in children could be explained by their ability to
      effectively compensate for such vestibular deficits.

PMID- 24882585
TI  - Temporary facial nerve dysfunction after parotidectomy correlates with tumor
      location.
AB  - OBJECTIVE: To investigate the clinical factors associated with temporary facial
      nerve dysfunction (TFND) following surgery for benign parotid gland tumors.
      METHODS: We reviewed the records of 175 patients with benign parotid gland tumors
      who underwent partial parotidectomy at Yokohama City University Medical Center in
      Japan. TFND was found in 33 patients (18.9%). We used two hypothetical lines in
      magnetic resonance imaging (MRI) images to define the tumor location (upper/lower
      or anterior/posterior) in the parotid gland. We then studied the associations of
      TFND with the following clinical factors: patient age, tumor size,
      histopathological diagnosis, and the location of the tumor within the parotid
      gland (superficial lobe/deep lobe; upper part/lower part; and anterior
      part/posterior part). RESULTS: Tumors located in the upper parts, anterior parts
      or the deep lobes of the parotid gland had statistically higher incidences of
      TFND compared with tumors located in the lower parts, posterior parts or the
      superficial lobe (P<0.001, <0.001, <0.01, respectively). The odds ratio for the
      risk of TFND was significantly high if tumors were located in the upper parts,
      the anterior parts or the deep lobes with stepwise multivariate regression
      analysis. The other factors, including patient's age, tumor size, histopathology
      of the tumor, and inadequate surgeon's experience, were not apparent risks for
      TFND. CONCLUSIONS: Parotid gland tumors located in the upper parts, the anterior
      parts or the deep lobes had a higher risk of TFND. The two hypothetical lines we
      used were shown to be useful to define the tumor location, eventually the risk of
      TFND.

PMID- 24882587
TI  - Effects of postural restriction after modified Epley maneuver on recurrence of
      benign paroxysmal positional vertigo.
AB  - OBJECTIVE: In the present study, we calculated the success rate of the modified
      Epley maneuver and determined the effectiveness of post-maneuver positional
      restriction in terms of the prevention of early and late recurrence. METHODS: The
      present study was conducted on 78 patients who had unilateral benign paroxysmal
      positional vertigo (BPPV) of the posterior semicircular canal (SCC) and who were
      treated in the Otorhinolaryngology Department of Susehri State Hospital. The Dix
      Hallpike test was performed on all patients. After the involved canal was
      identified using this test, we guided patients through the modified Epley
      repositioning maneuver. A maximum of two maneuvers were performed in the same
      session. The patients were randomly divided into two groups. One group was not
      advised any positional restriction, while the second group was advised positional
      restriction for 10 days after the procedure. Recurrences during 1-90 days after
      the treatment were noted as early recurrences, while those that occurred after 90
      days were noted as late recurrences. RESULTS: In the restriction group (n=39),
      repositioning was successful after a single maneuver in 32 (82.05%) patients and
      after two maneuvers in 5 (12.8%) patients. Repositioning failed in two (5.1%)
      patients. In the non-restriction group (n=39), repositioning was successful after
      a single maneuver in 31 (79.4%) patients and after two maneuvers in 6 (15.3%)
      patients. Repositioning failed in two (5.1%) patients. Thus, the success rate was
      94.8% in each group. Early recurrence occurred in 3 (8.1%) of 37 patients in the
      restriction group and 2 (5.4%) of 37 patients in the non-restriction group
      (p>0.05). Late recurrence occurred in 5 (13.5%) of 37 patients in both the
      restriction and non-restriction groups (p>0.05). CONCLUSION: Postural restriction
      after a canalith repositioning procedure does not improve procedural success or
      decrease early and late recurrence rates. However, the number of patients was too
      small to detect a difference between both treatment groups.

PMID- 24882588
TI  - Novel endoscopic scoring system after sinus surgery.
AB  - OBJECTIVE: To propose a simple post-operative endoscopic scoring system for use
      after endoscopic sinus surgery (ESS) in patients with chronic rhinosinusitis
      (CRS), and to demonstrate the usefulness of this approach. METHODS: Subjects
      comprised 116 patients (84 men, 32 women; mean age, 54 years) with CRS who were
      analyzed endoscopically and radiologically after ESS between 2006 and 2012. The
      study was designed as a case series with planned data collection in the setting
      of university medical centers. Patients were followed-up for >= 6 months after
      ESS (mean, 13.1 months). Both pre- and post-operative computed tomography (CT)
      findings of each sinus and olfactory cleft (OC) were scored according to the Lund
      Mackay scoring system: 0, normal; 1, partially; or 2, completely occupied. CT
      score represents the total score expressed as a percentage of the maximum
      possible score (12 points per side). Post-operative endoscopic score (E score, %)
      was calculated as the maximum score according to physical findings on each
      operated sinus and OC: 0, normal; 1, partially diseased; or 2, completely closed.
      Post-operative course using E score was verified by comparison with the Lund
      Kennedy (L-K) scoring system. RESULTS: E score was easily and quickly determined.
      Interclass correlation coefficient among 10 otolaryngologists indicated high
      level inter-rater reliability (0.922). E score correlated strongly with both CT
      score (n=116, p<0.0001, rs=0.755) and L-K score (n=79, p<0.0001, rs=0.723).
      CONCLUSION: Endoscopic evaluation using E score for sinuses and OCs after ESS is
      a useful method, together with L-K score for the nasal cavity and radiological
      study.

PMID- 24882589
TI  - Thielavialides A-E, nor-spiro-azaphilones, and a bis-spiro-azaphilone from
      Thielavia sp. PA0001, an endophytic fungus isolated from aeroponically grown
      Physalis alkekengi.
AB  - Four new nor-spiro-azaphilones, thielavialides A-D (1- 4), a new bis-spiro
      azaphilone, thielavialide E (5), together with pestafolide A (6), were isolated
      from the endophytic fungal strain, Thielavia sp. PA0001, occurring in the healthy
      leaf tissue of aeroponically grown Physalis alkekengi. The structures and
      relative configurations of 1-5 were established on the basis of their MS and NMR
      data. Possible biosynthetic pathways to thielavialides A-E (1- 5) from
      pestafolide A (6), some involving a Favorskii-like rearrangement, are proposed. 

PMID- 24882590
TI  - Conductive diamond sono-electrochemical disinfection (CDSED) for municipal
      wastewater reclamation.
AB  - In the present work, the disinfection of actual effluents from a municipal
      wastewater treatment plant (WWTP) by a conductive diamond sono-electrochemical
      process was assessed. First, efficiency of single electrodisinfection process
      with diamond anodes (without the contribution of ultrasounds) was studied,
      finding that the total disinfection can be attained at current charges applied
      below 0.02kAhm(-3). It was also found that the main disinfection mechanism is the
      attack of Escherichia coli (E. coli) by the disinfectants produced in the
      electrochemical cell and that the production of chlorates is avoided when working
      at current densities not higher than 1.27Am(-2). Next, a marked synergistic
      effect was found when coupling ultrasound (US) irradiation to the electrochemical
      system (sono-electrochemical disinfection). This increase in the disinfection
      rate was found to be related to the suppression of the agglomeration of E. coli
      cells and the enhancement in the production of disinfectant species. 

PMID- 24882591
TI  - Building a nano-crystalline alpha-alumina layer at a liquid metal/sapphire
      interface by ultrasound.
AB  - Transitional layers at the metal/ceramic interface play an very important role in
      ceramic joining. In this study, sapphire blocks were ultrasonically dipped in
      liquid Sn-Zn-Al alloy. It is found that the ultrasound promoted rapid oxidation
      reaction of aluminum at the Sn-Zn-Al/sapphire interface at 230 degrees C in the
      ambient atmosphere, resulting in the formation of a nano-crystalline alpha-Al2O3
      layer (NCAL). In a ~2nm boundary layer of the NCAL, the lattice matches the
      sapphire substrate well. Thus, a smooth transition of the lattice from sapphire
      to metal was formed through the NCAL. Ultrasonically soldered sapphire joints
      were made with Sn-Zn-Al as the filler alloy. Compressive shear strength of the
      joints reached 43-48MPa, which is relatively high comparing to other Al2O3 joints
      made of Sn alloys doped with Ti or Rear Earth elements. Thus, a new mechanism of
      ultrasonic soldering, i.e. building an oxide transitional layer on the surface of
      the solid, was revealed. We expect this sonochemical process to be applicable to
      other metal/oxide systems. 

PMID- 24882592
TI  - Metabolic syndrome: The association of obesity and unhealthy lifestyle among
      Malaysian elderly people.
AB  - The aim of this study is to investigate the prevalence of metabolic syndrome
      (MetS) and its predictors among Malaysian elderly. A total of 343 elderly aged >=
      60 years residing low cost flats in an urban area in the central of Malaysia were
      invited to participate in health screening in community centers. Subjects were
      interviewed to obtain socio demography, health status and behavior data.
      Anthropometric measurements were also measured. A total of 30 ml fasting blood
      was taken to determine fasting serum lipid, glucose level and oxidative stress.
      MetS was classified according to The International Diabetes Federation (IDF)
      criteria. The prevalence of MetS was 43.4%. More women (48.1%) were affected than
      men (36.3%) (p<0.05). Being obese or overweight was the strongest predictor for
      MetS in men and women (p<0.05, both gender). High carbohydrate intake increased
      risk of MetS in men by 2.8 folds. In women, higher fat free mass index, physical
      inactivity and good appetite increased risk of MetS by 3.9, 2.1 and 2.3 folds
      respectively. MetS affected almost half of Malaysian elderly being investigated,
      especially women, and is associated with obesity and unhealthy lifestyle. It is
      essential to develop preventive and intervention strategies to curb undesirable
      consequences associated with MetS.

PMID- 24882593
TI  - IGF-I and amino acids effects through TOR signaling on proliferation and
      differentiation of gilthead sea bream cultured myocytes.
AB  - Skeletal muscle growth and development is controlled by nutritional (amino acids,
      AA) as well as hormonal factors (insulin-like growth factor, IGF-I); however, how
      its interaction modulates muscle mass in fish is not clearly elucidated. The
      purpose of this study was to analyze the development of gilthead sea bream
      cultured myocytes to describe the effects of AA and IGF-I on proliferating cell
      nuclear antigen (PCNA) and myogenic regulatory factors (MRFs) expression, as well
      as on the transduction pathways involved in its signaling (TOR/AKT). Our results
      showed that AA and IGF-I separately increased the number of PCNA-positive cells
      and, together produced a synergistic effect. Furthermore, AA and IGF-I, combined
      or separately, increased significantly Myogenin protein expression, whereas MyoD
      was not affected. These results indicate a role for these factors in myocyte
      proliferation and differentiation. At the mRNA level, AA significantly enhanced
      PCNA expression, but no effects were observed on the expression of the MRFs or
      AKT2 and FOXO3 upon treatment. Nonetheless, we demonstrated for the first time in
      gilthead sea bream that AA significantly increased the gene expression of TOR and
      its downstream effectors 4EBP1 and 70S6K, with IGF-I having a supporting role on
      4EBP1 up-regulation. Moreover, AA and IGF-I also activated TOR and AKT by
      phosphorylation, respectively, being this activation decreased by specific
      inhibitors. In summary, the present study demonstrates the importance of TOR
      signaling on the stimulatory role of AA and IGF-I in gilthead sea bream
      myogenesis and contributes to better understand the potential regulation of
      muscle growth and development in fish. 

PMID- 24882594
TI  - The effect of platform switching on stress distribution in implants and
      periimplant bone studied by nonlinear finite element analysis.
AB  - STATEMENT OF PROBLEM: It is unknown whether dental implant systems with a
      platform-switched configuration have better periimplant bone stress distribution
      and lead to less periimplant bone level changes. PURPOSE: The purpose of this
      study was to quantitatively investigate interfacial stress and stress
      distribution in implant bone in 2 implant abutment designs (platform-switched
      design and conventional diameter matching) by using a nonlinear finite element
      analysis method. MATERIAL AND METHODS: A finite element simulation study was
      applied to 2 commercially available dental implant systems: the Ankylos implant
      system with a reduced-diameter abutment (platform-switched implant) and the
      Anthogyr implant system with an abutment of the same diameter (regular platform
      implant). These 2 dental implant systems were positioned in a bone block, which
      was constructed based on a cross-sectional image of a human mandible in the molar
      region. In simulation, a single vertical load of 50 N, 100 N, or 150 N and
      horizontal loads of 50 N and 100 N were applied to the occlusal surface of the
      abutment. RESULTS: The finite element analysis found that the Ankylos implant
      system has a higher maximum von Mises stress in the implant abutment connection
      section and a lower maximum von Mises stress in the periimplant bone. The
      opposite results were found in the Anthogyr implant system. CONCLUSIONS: Lower
      stress levels in the periimplant bone with a more uniform stress distribution
      were found for the Ankylos implant system with a platform-switched configuration.
      Although relatively higher stress was found in the abutment, premature implant
      failure is not anticipated because of the high strength of titanium alloy.

PMID- 24882595
TI  - Intraoral scanning of hard and soft tissues for partial removable dental
      prosthesis fabrication.
AB  - This article provides proof of concept for the use of intraoral scanning
      technology to record hard and soft tissue morphology for the fabrication of a
      cast partial removable dental prosthesis. An open source intraoral scanner was
      used to scan the hard and soft tissues to create a stereolithographic file that
      was subsequently imported into a computer-aided design software program for the
      digital/virtual design of a partial removable dental prosthesis framework.
      Computer-aided design and computer-aided manufacturing technology was then used
      to fabricate a resin framework that was trial placed to evaluate accuracy and for
      conventional investing and casting with a cobalt-chromium alloy. The cast
      framework and definitive prosthesis were judged to be clinically accurate in fit,
      stability, and retention. 

PMID- 24882596
TI  - Prosthetic procedure for simultaneous immediate loading of opposing edentulous
      arches.
AB  - For patients with complete edentulism, a significant problem is the transfer of
      diagnostic data to the definitive casts when an immediate loading technique is
      used. This article presents a prosthetic procedure to allow simultaneous
      treatment of opposing edentulous arches with immediate implant loading. This
      technique uses 2 occlusal acrylic resin devices to transfer the diagnostic cast
      information to the definitive casts. Esthetic and functional fixed dental
      prostheses are fabricated from diagnostic information acquired in the presurgical
      phase without any impression or recording of the maxillomandibular relationship
      during or after surgery. This methodology is applicable when the simultaneous
      immediate loading of implants in 2 edentulous arches is indicated. 

PMID- 24882597
TI  - Shore hardness and tensile bond strength of long-term soft denture lining
      materials.
AB  - STATEMENT OF PROBLEM: Reduced softness and separation from the denture base are
      the most significant problems of long-term soft lining materials. PURPOSE: The
      purpose of this study was to evaluate the durometer Shore A hardness and tensile
      bond strength of long-term soft denture lining materials and to investigate the
      correlation between these 2 properties. MATERIAL AND METHODS: A group of 7 soft
      lining materials, 6 silicone based (Dentusil, GC Reline Soft, GC Reline
      Ultrasoft, Mucopren Soft, Mucosoft, Sofreliner Tough) and 1 acrylic resin based
      (Durabase), were evaluated for durometer Shore A hardness and tensile bond
      strength to heat-polymerized denture base resin (Lucitone 199). A specially
      designed split mold and loading assembly with a swivel connector were used for
      the durometer Shore A hardness test and tensile bond strength test to improve
      accuracy and facilitate measurement. Three specimens of each product were stored
      in a 37 degrees C water bath, and durometer Shore A hardness tests were carried
      out after 24 hours and 28 days. A tensile bond strength test was carried out for
      10 specimens of each product, which were stored in a 37 degrees C water bath for
      24 hours before the test. Repeated-measures ANOVA, the Kruskal-Wallis and Duncan
      multiple range tests, and the Spearman correlation were used for statistical
      analyses. RESULTS: The repeated-measures ANOVA found significant durometer Shore
      A hardness differences for the materials (P<.001) and the interaction effect
      (aging*materials) (P<.001). GC Reline Ultrasoft showed the lowest mean durometer
      Shore A hardness (21.30 +/-0.29 for 24 hours, 34.73 +/-0.47 for 28 days), and GC
      Reline Soft showed the highest mean durometer Shore A hardness (50.13 +/-0.48 for
      24 hours, 57.20 +/-0.28 for 28 days). The Kruskal-Wallis test found a significant
      difference in the mean tensile bond strength values (P<.001). GC Reline Ultrasoft
      (0.82 +/-0.32 MPa) and Mucopren Soft (0.96 +/-0.46 MPa) had a significantly lower
      mean tensile bond strength (P<.05). GC Reline Soft had the highest mean tensile
      bond strength (2.99 +/-0.43 MPa) (P<.05), and acrylic resin-based Durabase showed
      a significantly different tensile bond strength (1.32 +/-0.16 MPa), except for
      Mucopren Soft, among the materials (P<.05). The tensile bond strength and Shore A
      hardness showed a statistically insignificant moderate positive correlation
      (r=0.571, P=.180 for Shore A hardness 24 hours versus tensile bond strength;
      r=0.607, P=.148 for Shore A hardness 28 days versus tensile bond strength).
      CONCLUSIONS: Within the limitations of this study, significant differences were
      found in durometer Shore A hardness (with aging time) and tensile bond strength
      among the materials. Adhesive failure was moderately correlated with durometer
      Shore A hardness, especially after 28 days, but was not significant.

PMID- 24882598
TI  - A prospective multicenter study of immediate function of 1-piece implants: a 3
      year follow-up report.
AB  - STATEMENT OF PROBLEM: Although 1-piece implants are associated with positive
      clinical outcomes, including improved implant stability, overall survival rate,
      and marginal bone levels, a few studies have suggested that 1-piece implants have
      low success rates. PURPOSE: This prospective multicenter study evaluated the
      efficacy of 1-piece implants placed in immediate function in private clinic-based
      and hospital-based settings with a focus on marginal bone level changes and
      esthetic outcomes over a 3-year follow-up period. MATERIAL AND METHODS: A total
      of 93 one-piece implants (29 maxillary, 64 mandibular) were placed in 63
      participants (25 men and 38 women) at 1 university hospital and 3 private
      clinics. The implants were restored with interim crowns immediately after
      placement. Clinical and radiographic evaluations of marginal bone level, implant
      stability, periimplant mucosa, and plaque and papilla indices were performed at
      the time of implantation and after 6, 12, 24, and 36 months. RESULTS: The 3-year
      cumulative implant survival rate was 100%. After implant placement, mean bone
      levels changed from -0.16 +/-1.41 mm at 24 months to 0.40 +/-1.46 mm at 36
      months. Clinical parameters, including implant stability, periimplant mucosa, and
      plaque index, remained stable from 3 to 36 months during follow-up. The papilla
      index score increased over time. CONCLUSIONS: Within the limitations of this
      prospective study, marginal bone level was maintained, soft tissue integration
      was achieved, and a cumulative survival rate of 100% was obtained for 1-piece
      implants. The present findings indicate that 1-piece implants are an effective
      treatment option for immediate function situations.

PMID- 24882599
TI  - Outpatient multimodality management of large submucosal myomas using transvaginal
      radiofrequency myolysis.
AB  - STUDY OBJECTIVE: To evaluate the safety and efficacy of transvaginal
      radiofrequency myolysis (RFM) with or without combined hysteroscopy for treatment
      of large submucosal leiomyomas with a substantial intramural portion. DESIGN:
      Retrospective observational study (Canadian Task Force classification III).
      SETTING: Hospital outpatient department. PATIENTS: Twenty-four patients with
      large submucosal leiomyomas with a substantial intramural portion. INTERVENTIONS:
      Transvaginal RFM with or without combined hysteroscopy. MEASUREMENTS AND MAIN
      RESULTS: Twenty-four patients with large submucosal leiomyomas with a substantial
      intramural portion were enrolled to undergo stepwise RFM. Additional
      hysteroscopic myomectomy was performed in 6 patients at 3 to 6 months after RFM.
      Myoma volumes were measured via 3-dimensional ultrasonography before RFM and at
      1, 3, 6, 12, and 24 months postoperatively. Symptom severity was assessed using
      the Uterine Fibroid Symptom and Quality of Life questionnaire and the Health
      Related Quality of Life questionnaire. The total volume reduction rate 24 months
      postoperatively was 84.2%. Symptom severity and health-related quality of life
      scores demonstrated substantial improvements at 12 months after RFM. CONCLUSIONS:
      RFM with or without hysteroscopy is an effective treatment for large myomas with
      deep intramural positioning, and it seems safe for use in all patients with
      submucosal myoma-related symptoms.

PMID- 24882600
TI  - Shoulder pain following laparoscopic surgery: can we block the referral?

PMID- 24882601
TI  - Liquid chromatography coupled with fluorimetric detection and third derivative
      synchronous fluorescence spectroscopy as two analytical methods for the
      simultaneous determination of rabeprazole sodium and domperidone after
      derivatization with 4-chloro-7-nitrobenzofurazan.
AB  - Two simple, sensitive, rapid, economic and validated methods, namely reversed
      phase liquid chromatography (method Iota) and third derivative synchronous
      fluorescence spectroscopy (method IotaIota) have been developed for the
      simultaneous determination of rabeprazole sodium and domperidone in their
      laboratory prepared mixture after derivatization with 4-Chloro-7
      nitrobenzofurazan. Reversed phase chromatography was conducted using a Zorbax(r)
      SB-Phenyl column (250.0 mm * 4.6 mm id) combined with a guard column at ambient
      temperature with fluorimetric detection at 540 nm after excitation at 483 nm. A
      mobile phase composed of a mixture of distilled water with methanol and
      acetonitrile in a ratio of 50:20:30 adjusted pH to 4 has been used at a flow rate
      of 1 mL/min. Sharp well resolved peaks were obtained for domperidone and
      rabeprazole sodium with retention times of 5.5 and 6.4 min respectively. While in
      method IotaIota, the third-derivative spectra were estimated at 507 and 436 nm
      for rabeprazole sodium and domperidone respectively. Linearity ranges for
      rabeprazole sodium and domperidone respectively in both methods were found to be
      0.15-2.0 and 0.1-1.5 MUg/mL. The proposed methods were successfully applied for
      the analysis of the two compounds in their binary mixtures, and laboratory
      prepared tablets. The obtained results were favorably compared with those
      obtained by the comparison method. Furthermore, detailed validation procedure was
      also conducted.

PMID- 24882602
TI  - Fluorescent coumarin derivatives with viscosity sensitive emission--synthesis,
      photophysical properties and computational studies.
AB  - New derivatives of (benzo[d]azolyl)-benzo[f]chromenone were synthesized from the
      intermediate 3-(1,3-benzazol-2-yl)naphthalen-2-ol, obtained from 3
      hydroxynaphthalene-2-carboxylic acid and 2-amino phenol in the presence of PCl3
      in chlorobenzene at 130-135  degrees C. The compounds were characterized by FT
      IR, (1) H NMR, mass spectroscopy and elemental analysis. The synthesized
      compounds are fluorescent which absorb in the range of 296 to 332 nm while emit
      in the range of 368 to 404 nm. The experimental absorption and emission
      wavelengths for the compounds 5 and 6 are in good agreement with those predicted
      using the Time-Dependent Density Functional Theory (TD-DFT) [B3LYP/6-31G(d)]. The
      largest wavelength difference between the experimental and computed absorption
      maxima was 29 nm (tetrahedrofuran) for compound 5 while for emission it was 61 nm
      (dichloromethane) for compound 7. The emission intensities of all the compounds
      decrease continuously as the viscosity of the microenvironment increases. The
      compounds are thermally stable up to a temperature range of 300 to 350  degrees
      C.

PMID- 24882603
TI  - Layer-dependent electrical and optoelectronic responses of ReSe2 nanosheet
      transistors.
AB  - The ability to control the appropriate layer thickness of transition metal
      dichalcogenides (TMDs) affords the opportunity to engineer many properties for a
      variety of applications in possible technological fields. Here we demonstrate
      that band-gap and mobility of ReSe2 nanosheet, a new member of the TMDs, increase
      when the layer number decreases, thus influencing the performances of ReSe2
      transistors with different layers. A single-layer ReSe2 transistor shows much
      higher device mobility of 9.78 cm(2) V(-1) s(-1) than few-layer transistors (0.10
      cm(2) V(-1) s(-1)). Moreover, a single-layer device shows high sensitivity to red
      light (633 nm) and has a light-improved mobility of 14.1 cm(2) V(-1) s(-1).
      Molecular physisorption is used as "gating" to modulate the carrier density of
      our single-layer transistors, resulting in a high photoresponsivity (Rlambda) of
      95 A W(-1) and external quantum efficiency (EQE) of 18 645% in O2 environment.
      This work highlights the fact that the properties of ReSe2 can be tuned in terms
      of the number of layers and gas molecule gating, and single-layer ReSe2 with
      appropriate band-gap is a promising material for future functional device
      applications. 

PMID- 24882604
TI  - The effects of preoperative, video-assisted anesthesia education in Spanish on
      Spanish-speaking patients' anxiety, knowledge, and satisfaction: a pilot study.
AB  - We studied the effect of an instructional video in Spanish on self-reported
      anxiety, knowledge about general anesthesia procedures, and satisfaction with the
      preoperative anesthesia process in patients requiring a Spanish interpreter. This
      prospective, randomized, nonblinded pilot study took place at Massachusetts
      General Hospital (MGH), a university-affiliated tertiary-care hospital. Twenty
      adult, ASA physical status 1, 2, and 3 patients, scheduled for elective surgery
      (gynecological, orthopedic, and intrabdominal surgery) during general anesthesia
      were studied. Anxiety, knowledge, and patient satisfaction were assessed using a
      visual analog scale (VAS). There was a significant reduction in anxiety score in
      patients who viewed the video compared with those who did not (median reduction 2
      vs 0; P = 0.020). There was an increase in satisfaction score in the video group
      (median increase 2 vs 0; P = 0.046). There was no difference in reported
      knowledge-improvement scores between the two groups (3.5 vs 4; P = 0.908). In
      Spanish-speaking patients, the addition of an instructional video in Spanish to a
      preanesthesia interview decreased anxiety and increased patient satisfaction. 

PMID- 24882605
TI  - A placebo-controlled trial of midazolam as an adjunct to morphine patient
      controlled analgesia after spinal surgery.
AB  - STUDY OBJECTIVE: To investigate the potential benefit of postoperatively
      providing a patient-controlled anxiolytic agent, midazolam, in addition to
      morphine. DESIGN: A double-blinded, placebo-controlled trial of patient
      controlled midazolam. SETTING: A Community hospital. PARTICIPANTS: 29 patients
      undergoing elective spinal surgery. INTERVENTIONS: Postoperatively, via two
      separate patient-controlled pumps, the treatment group received morphine and
      midazolam, and the control group received morphine and saline solution.
      MEASUREMENTS: Repeated measures using numerical rating scales of the primary
      outcomes of pain and anxiety were obtained every two hours postoperatively.
      Amount of morphine and midazolam/placebo administered was assessed, as were other
      secondary outcomes. MAIN RESULTS: Anxiety level in the treatment group declined
      more rapidly over the 24 hours after surgery than in the control group. The
      treatment group used less morphine than the control. Preoperative positive affect
      was the only significant psychological predictor of postoperative outcomes.
      CONCLUSIONS: Patients who received both midazolam and morphine experienced a more
      rapid decline in anxiety and used less opioid medication than those receiving
      morphine alone.

PMID- 24882606
TI  - Comparison of posterior and subcostal approaches to ultrasound-guided transverse
      abdominis plane block for postoperative analgesia in laparoscopic
      cholecystectomy.
AB  - STUDY OBJECTIVE: To evaluate the effectiveness of subcostal TAP block and to
      compare its efficacy with that of posterior TAP block in decreasing postoperative
      pain in patients undergoing laparoscopic cholecystectomy during general
      anesthesia. DESIGN: Prospective, randomized, double-blind study. SETTING:
      Academic medical center. PATIENTS: 60 adult, ASA physical status 1 and 2 patients
      of both genders, aged 18-60 years, scheduled for elective laparoscopic
      cholecystectomy. INTERVENTIONS: Patients were randomized to three groups of 20
      patients each. Group 1 patients received standard general anesthesia (control
      group); Group 2 patients received an ultrasound-guided posterior TAP block using
      15 mL of 0.375% ropivacaine on each side; and Group 3 patients underwent a
      subcostal TAP block with 15 mL of 0.375% ropivacaine on each side. MEASUREMENTS:
      The presence and severity of pain during rest and movement, as well as nausea or
      vomiting and sedation, were assessed in all patients postoperatively on PACU
      admission, then at 2, 4, 6, 8, 12, and 24-hour intervals. Patients with a visual
      analog score (VAS) greater than 4, or those requesting analgesic were given
      intravenous tramadol 2 mg/kg as an initial dose; subsequent 1 mg/kg doses of
      tramadol, if needed, were given. RESULTS: Patients who received a subcostal TAP
      block had significantly lower pain scores at rest and on movement than the
      control group at all times postoperatively. Although, in the initial
      postoperative measurement times, the subcostal and posterior TAP groups had
      comparable pain scores, after 4 hours these scores were significantly lower in
      patients who had received the subcostal TAP block. CONCLUSION: For incisions
      mainly involving the supra-umbilical region, subcostal TAP block may be a better
      alternative than the posterior approach for providing postoperative analgesia.

PMID- 24882608
TI  - Concentration and temperature dependence of the viscosity of polyol aqueous
      solutions.
AB  - The concentration and temperature dependence of the viscosity of supercooled
      polyol (sucrose, trehalose, glucose and glycerol) aqueous solutions was analyzed
      with the aim of finding simple and accurate correlation equations for the
      description of this transport property. Three different equations were examined
      and compared, two empirical equations and an equation derived from the Avramov
      Milchev (AM) model. If a description of the viscosity temperature dependence is
      intended, the AM model gives the best representation of the experimental data
      with only two adjustable parameters, which have a clear physical meaning.
      However, if we focus on both, temperature and concentration dependence, the
      empirical equations are found to be superior to the AM model, except for the
      glycerol aqueous system. The AM model includes a parameter related to the system
      fragility, which was obtained for all the aqueous polyol mixtures previously
      mentioned as a function of concentration, and also for water-trehalose-sodium
      tetraborate mixtures as a function of the electrolyte content. The results show
      that the fragility parameter increases with polyol concentration in the series
      glycerol<glucose~sucrose<trehalose, and that the addition of sodium tetraborate
      to aqueous trehalose solutions increases the fragility of the mixtures. Our
      results imply that the hypothesis relating the low fragility of the aqueous
      mixtures with their high cryo or dehydroprotection capabilities is not valid.

PMID- 24882607
TI  - Supraventricular tachycardia during pediatric anesthesia: a case series and
      qualitative analysis.
AB  - STUDY OBJECTIVE: To perform a qualitative analysis of noncardiac patients who
      developed suspected intraoperative supraventricular tachycardia (SVT) during
      general anesthesia. DESIGN: Retrospective database analysis and chart review.
      SETTING: Operating room of a university-affiliated children's hospital.
      MEASUREMENTS: The records of children without cardiac disease who received
      general anesthesia at The Children's Hospital of Philadelphia from July 1998
      through June 2011 were reviewed. Patients with heart rate values above 180 beats
      per minute were identified, as were specific medications or key words in the free
      text fields of the anesthesia records that would be indicative of a
      tachyarrhythmia. Each case was reviewed by at least two authors; each patient was
      assigned a diagnosis classification of "highly suspicious" or "unlikely" SVT. The
      highly suspicious SVT cases were examined in detail to determine the specific
      aims. MAIN RESULTS: 36 subjects out of a total of 285,353 anesthetics
      administered during the study period were suspected by the anesthesia care team
      to have had an episode of intraoperative SVT: 22 were "highly suspicious" events,
      and 14 were "unlikely" events. The highly suspicious SVT events occurred in all
      phases of anesthesia, and none led to any hemodynamic instability. Effective
      treatments included vagal maneuvers, pharmacologic antiarrhythmics, or no
      treatment if the event resolved spontaneously before treatment. Six patients had
      outpatient follow-up and three received antiarrhythmic medications to control
      ongoing SVT. CONCLUSIONS: SVT during the intraoperative period in noncardiac
      pediatric patients was uncommon. When it occurred, it was not associated with
      clinically significant patient morbidity. For some patients, the anesthesia
      unmasked a predisposition for re-entrant SVT and those patients remained on
      maintenance antiarrhythmic therapy following discharge home.

PMID- 24882610
TI  - Stimulation of postsynapse adrenergic alpha2A receptor improves
      attention/cognition performance in an animal model of attention deficit
      hyperactivity disorder.
AB  - A 5-trial inhibitory avoidance test using spontaneously hypertensive rat (SHR)
      pups has been used as an animal model of attention deficit hyperactivity disorder
      (ADHD). However, the roles of noradrenergic systems, which are involved in the
      pathophysiology of ADHD, have not been investigated in this model. In the present
      study, the effects of adrenergic alpha2 receptor stimulation, which has been an
      effective treatment for ADHD, on attention/cognition performance were
      investigated in this model. Moreover, neuronal mechanisms mediated through
      adrenergic alpha2 receptors were investigated. We evaluated the effects of both
      clonidine, a non-selective adrenergic alpha2 receptor agonist, and guanfacine, a
      selective adrenergic alpha2A receptor agonist, using a 5-trial inhibitory
      avoidance test with SHR pups. Juvenile SHR exhibited a shorter transfer latency,
      compared with juvenile Wistar Kyoto (WKY) rats. Both clonidine and guanfacine
      significantly prolonged the transfer latency of juvenile SHR. The effects of
      clonidine and guanfacine were significantly blocked by pretreatment with an
      adrenergic alpha2A receptor antagonist. In contrast, the effect of clonidine was
      not attenuated by pretreatment with an adrenergic alpha2B receptor antagonist, or
      an adrenergic alpha2C receptor antagonist, while it was attenuated by a non
      selective adrenergic alpha2 receptor antagonist. Furthermore, the effects of
      neither clonidine nor guanfacine were blocked by pretreatment with a selective
      noradrenergic neurotoxin. These results suggest that the stimulation of the
      adrenergic alpha2A receptor improves the attention/cognition performance of
      juvenile SHR in the 5-trial inhibitory avoidance test and that postsynaptic,
      rather than presynaptic, adrenergic alpha2A receptor is involved in this effect. 

PMID- 24882609
TI  - Long-term effects of controllability or the lack of it on coping abilities and
      stress resilience in the rat.
AB  - Findings suggest that stress-induced impaired learning and coping abilities may
      be attributed more to the psychological nature of the stressor, rather than its
      physical properties. It has been proposed that establishing controllability over
      stressors can ameliorate some of its effects on cognition and behavior. Gaining
      controllability was suggested to be associated with the development of stress
      resilience. Based on repeated exposure to the two-way shuttle avoidance task, we
      previously developed and validated a behavioral task that leads to a strict
      dissociation between gaining controllability (to the level that the associated
      fear is significantly reduced) and a fearful state of uncontrollability.
      Employing this protocol, we investigated here the impact of gaining or failing to
      gain emotional controllability on indices of anxiety and depression and on
      subsequent abilities to cope with positively or negatively reinforcing learning
      experiences. In agreement with previous studies, rats exposed to the
      uncontrollable protocol demonstrated high concentration of sera corticosterone,
      increased immobility, reduced duration of struggling in the forced swim test and
      impaired ability to acquire subsequent learning tasks. Achieving emotional
      controllability resulted in resilience to stress as was indicated by longer
      duration of struggling in the forced swim test, and enhanced learning abilities.
      Our prolonged training protocol, with the demonstrated ability of rats to gain
      emotional controllability, is proposed as a useful tool to study the
      neurobiological mechanisms of stress resilience.

PMID- 24882611
TI  - Loudness perception affected by high doses of salicylate--a behavioral model of
      hyperacusis.
AB  - The major side-effects of high doses of salicylate include sensorial hearing loss
      and tinnitus. Although salicylate decreases cochlear output, it enhances the
      evoked potentials recorded from the central auditory system (CAS), suggesting an
      increase to sound sensitivity. However, the loudness change after salicylate
      administration has not yet been directly measured. In this study, we established
      an operant conditioning based behavioral task in rats and measured their loudness
      perception changes before and after high doses of salicylate injection (250
      mg/kg, i.p.). We found that high doses of salicylate induced a significant
      increase to loudness response in 40% of the rats (out of 20 rats), suggesting a
      hyperacusis behavior. In another 40% of rats, a rapid increase of loudness
      response was detected, suggesting loudness recruitment. The reaction time of the
      rats was also measured during the loudness tests before and after salicylate
      exposure. The reaction time level functions are highly correlated to the loudness
      response functions. Our studies confirmed that increased sound sensitivity, which
      is commonly seen in patients with tinnitus and hyperacusis, can be induced by
      high doses of salicylate. This loudness change induced by salicylate may be
      related with hypersensitivity in the CAS.

PMID- 24882612
TI  - Traumatic dislocation of posterior tibial tendon by avulsion of flexor
      retinacular release. Reconstruction with suture anchors.
AB  - INTRODUCTION: Traumatic dislocation of the posterior tibial tendon (PTT) has a
      very low prevalence. It presents with pain and recurrent snapping on the
      posterior side of the medial malleolus after an ankle sprain while practicing
      sports. The diagnosis is based on clinical examination, supported by imaging
      techniques. The treatment must be always surgical. CASE REPORT: A 28 year old man
      sprained ankle his ankle while jogging. He was treated in an emergency department
      with an elastic bandage. Once he recovered, he went back to running, noticing a
      projection with ankle pain. In the physical examination the PTT was reproduced
      with inversion maneuvers and forced dorsiflexion. Ultrasound and MRI were
      performed on the ankle. The patient was operated on, leaving a stable ankle with
      no projection. Three months later he had no pain and restarted his physical
      activities. CONCLUSION: Surgical treatment of PTT dislocation by re-anchoring the
      flexor retinacula provides an excellent functional outcome.

PMID- 24882613
TI  - Unilateral eczema on the dorsum of the hand.

PMID- 24882614
TI  - Drug survival in biologic therapy. Do we know what it means? Can we calculate it?

PMID- 24882615
TI  - Introduction: MicroRNAs in human reproduction: small molecules with crucial
      regulatory roles.
AB  - MicroRNAs constitute a large family of approximately 21-nucleotide-long,
      noncoding RNAs. They emerged more than 20 years ago as key posttranscriptional
      regulators of gene expression. The regulatory role of these small RNA molecules
      has recently begun to be explored in the human reproductive system. In this
      issue's Views and Reviews, the authors present the current knowledge regarding
      the involvement of microRNAs in several aspects of human reproduction and discuss
      its future implications for clinical practice.

PMID- 24882616
TI  - Regulatory role of microRNAs in ovarian function.
AB  - MicroRNAs have recently begun to be explored in ovarian cells, uncovering their
      influence on fundamental ovarian features like steroidogenesis, ovulation, and
      curpos luteum development and function. We provide a review of the current
      knowledge on microRNAs, specifically relating to human ovarian cell function and
      microRNAs' role in the ovarian physiologic process and ovulation dysfunction.
      Because of microRNAs' known stability in body fluids, we enlighten also their
      potential use in the clinical setting as novel biomarkers for ovarian function.
      Future research of the role of microRNAs in physiologic and dysfunctional
      ovulation may offer new diagnostic and treatment strategies for infertility and
      other ovarian disorders. 

PMID- 24882617
TI  - MicroRNA and implantation.
AB  - We provide a review of microRNA (miRNA) related to human implantation which shows
      the potential diagnostic role of miRNAs in impaired endometrial receptivity,
      altered embryo development, implantation failure after assisted reproduction
      technology, and in ectopic pregnancy and pregnancies of unknown location.
      MicroRNAs may be emerging diagnostic markers and potential therapeutic tools for
      understanding implantation disorders. However, further research is needed before
      miRNAs can be used in clinical practice for identifying and treating implantation
      failure. 

PMID- 24882618
TI  - MicroRNA and gynecological reproductive diseases.
AB  - MicroRNAs (miRNAs) are a class of small non-coding RNAs estimated to regulate the
      translation of mRNAs in 30% of all genes in animals by inhibiting translation.
      Aberrant miRNA expression is associated with many human diseases, including
      gynecological diseases, cancer, inflammatory diseases, and cardiovascular
      disorders. Abnormal expression of miRNAs has been observed in multiple human
      reproductive tract diseases including preeclampsia, endometrioid endometrial
      adenocarcinoma, uterine leiomyomata, ovarian carcinoma, endometriosis, and
      recurrent pregnancy loss. In the following review, an update of the role of
      microRNA and gynecological diseases is performed covering, not only impact of
      microRNA dysregulation in the origin of each disease, but also showing the
      potential useful diagnostic and therapeutic tool that miRNA may play in these
      gynecological pathologies. 

PMID- 24882619
TI  - MicroRNAs and spermatogenesis.
AB  - In mammals, male gametes are produced inside the testis by spermatogenesis, which
      has three phases: mitotic proliferation of spermatogonia, meiosis of
      spermatocytes, and haploid differentiation of spermatids. The genome of male germ
      cells is actively transcribed to produce phase-specific gene expression patterns.
      Male germ cells have a complex transcriptome. In addition to protein-coding
      messenger RNAs, many noncoding RNAs, including microRNAs (miRNAs), are produced.
      The miRNAs are important regulators of gene expression. They function mainly post
      transcriptionally to control the stability or translation of their target
      messenger RNAs. The miRNAs are expressed in a cell-specific manner during
      spermatogenesis to participate in the control of each step of male germ cell
      differentiation. Genetically modified mouse models have demonstrated the
      importance of miRNA pathways for normal spermatogenesis, and functional studies
      have been designed to dissect the roles of specific miRNAs in distinct cell
      types. Clinical studies have exploited the well-defined expression profiles of
      miRNAs, and human spermatozoal or seminal plasma miRNAs have been explored as
      potential biomarkers for male factor infertility. This review article discusses
      the current findings that support the central role of miRNAs in the regulation of
      spermatogenesis and male fertility. 

PMID- 24882620
TI  - The association between low-density lipoprotein cholesterol goal attainment,
      physician and patient attitudes and perceptions, and healthcare policy.
AB  - AIM: Withholding effective treatment is clinically prevalent. The CEntralized Pan
      Asian survey on tHE Under-treatment of hypercholeSterolemia (CEPHEUS-PA)
      indicated suboptimal low-density lipoprotein cholesterol (LDL-C) goal attainment
      in Taiwan, which may be attributable to clinical inertia. We herein analyzed the
      Taiwanese cohort in the CEPHEUS-PA to identify key elements regarding clinical
      inertia and unsatisfactory LDL-C control. METHODS: A questionnaire regarding the
      attitudes and perceptions for each physician and patient was included in the
      CEPHEUS-PA. Physicians completed the physician questionnaire before enrolling
      patients, who completed the patient questionnaire before the assessment. RESULTS:
      The National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP
      III) guideline was used by 81.8% of physicians to establish the individual
      therapeutic targets; 50.2% of patients failed to take medications persistently.
      Regarding perceptions to hypercholesterolemia management, 75.9% of physicians
      were confident of having a sufficient number of patients at cholesterol targets;
      80.2% and 65.9% of patients felt satisfied and motivated, respectively, but 46.0%
      had no strong feeling. The healthcare reimbursement policy used for treatment
      guidance was a significant determinant for LDL-C goal attainment (OR=0.32, 95%
      CI: 0.15-0.69, P=0.006) in addition to patient compliance. Low patient
      involvement indexed by having no strong feeling was associated with poor LDL-C
      control (OR=0.73, 95% CI: 0.56-0.95, P=0.020). CONCLUSIONS: The referenced
      healthcare reimbursement policy, poor patient compliance, and low patient
      involvement with hypercholesterolemia management were associated with failure of
      LDL-C control. Our findings highlight the need to overcome those barriers to
      improve the under-treatment of hypercholesterolemia.

PMID- 24882621
TI  - Serum apolipoprotein B-48 concentration is associated with a reduced estimated
      glomerular filtration rate and increased proteinuria.
AB  - AIM: Apolipoprotein B-48 (apoB-48) is a constituent of chylomicrons and their
      remnants (chylomicron remnants). A high concentration of serum apoB-48 is
      suspected to be a major risk factor for the development of atherosclerotic
      cardiovascular disease. Proteinuria and a reduced estimated glomerular filtration
      rate (eGFR) are independent risk factors for cardiovascular events and renal
      dysfunction. In the present study, we examined whether the serum apoB-48
      concentration is associated with renal dysfunction. METHODS: A total of 264
      patients was enrolled and classified into four groups according to the eGFR and
      level of proteinuria: a high eGFR (>60mL/min/1.73m(2)) without proteinuria (>=1+
      by urine dipstick) (n=50); a high eGFR with proteinuria (n=75); a low eGFR
      (>60mL/min/1.73m(2)) without proteinuria (n=74); and a low eGFR with proteinuria
      (n=65). Biochemical markers of lipid metabolism, including the fasting serum apoB
      48 concentration, were compared between the four groups. RESULTS: The serum log
      apoB-48 and log-apoB-48/TG levels were significantly higher in the patients with
      a high eGFR with proteinuria, low eGFR with proteinuria and low eGFR without
      proteinuria than in those with a high eGFR without proteinuria, with the most
      significant differences for these parameters. The eGFR was found to be
      significantly correlated with the log-apoB-48 and log-apoB-48/TG levels, whereas
      urinary protein was found to be significantly correlated with the log-apoB-48
      level only. A multiple regression analysis indicated that the log-apoB-48/TG
      level was a significant determinant of a reduced eGFR. CONCLUSIONS: Both a low
      eGFR (<60) and proteinuria (>=1+) are independent determinants of a high apoB-48
      concentration. Taken together, the present results suggest that an increased
      serum apoB-48 concentration contributes to an increased risk of cardiovascular
      events.

PMID- 24882622
TI  - The oncoprotein HBXIP up-regulates SCG3 through modulating E2F1 and miR-509-3p in
      hepatoma cells.
AB  - Hepatitis B X-interacting protein (HBXIP) is an important oncoprotein in
      hepatocarcinogenesis. Here, we found that the expression levels of HBXIP were
      positively associated with those of Secretogranin III (SCG3) in clinical
      hepatocellular carcinoma tissues. We identified that HBXIP up-regulated the
      expression of SCG3 through modulating both E2F transcription factor 1 (E2F1) and
      miR-509-3p. HBXIP suppressed miR-509-3p through activating NF-kappaB. In
      function, we showed that SCG3 increased the proliferation of hepatoma cells and
      HBXIP enhanced the proliferation of the cells via SCG3 in vitro and in vivo.
      Thus, we conclude that HBXIP facilitates the proliferation of hepatoma cells
      through up-regulating SCG3.

PMID- 24882623
TI  - Comment on: targeting homologous recombination-mediated DNA repair in cancer.

PMID- 24882625
TI  - Enantioselective Prins cyclization: BINOL-derived phosphoric acid and CuCl
      synergistic catalysis.
AB  - The first catalytic enantioselective Prins cyclization is disclosed. The reaction
      is catalyzed by the combination of a chiral BINOL-derived bis-phosphoric acid and
      CuCl. The process consists of a tandem Prins/Friedel-Crafts cyclization that
      affords the hexahydro-1H-benzo[f]isochromenes products with three new contiguous
      stereogenic centers in high yields, and good enantio- and excellent
      diastereoselectivities. 

PMID- 24882626
TI  - E-cigarettes--prevention, pulmonary health, and addiction.
AB  - BACKGROUND: E-cigarettes are coming into wider use. They are advertised as an aid
      to smoking cessation, but there is concern that they may also serve as a gateway
      drug for cigarette smoking. METHOD: The authors systematically searched the
      PubMed database for relevant publications on the mechanism of action of e
      cigarettes, the nature of their emissions, their assessment by potential users,
      their efficacy in smoking cessation, and their potential for addiction. RESULTS:
      There have been many reports of epidemiologically uninformative case series in
      which smokers were helped to stop smoking by the use of e- cigarettes. Only two
      controlled trials have shown that e-cigarettes have approximately the same effect
      as nicotine substitution therapy when used as an aid to smoking cessation. The
      effect is nearly independent of nicotine content. E-cigarettes are also consumed,
      to a small extent, by nonsmokers. As far as can be estimated toxicologically at
      present, the danger to active and passive smokers of e-cigarettes is presumably
      orders of magnitude less than that of tobacco smokers, although the variable
      composition of the fluids used in e-cigarettes introduces a degree of
      uncertainty. CONCLUSION: Preclinical and initial clinical data, including some
      data from randomized controlled trials, indicate that e-cigarettes may be useful
      as an aid to smoking cessation or as a means of lowering risk in high-risk
      groups. In contrast to the demonstrated efficacy of multimodal smoking-cessation
      programs with pharmacological and psychotherapeutic support, the efficacy of e
      cigarettes in smoking cessation has not yet been satisfactorily shown. Valid and
      informative clinical trials are urgently needed. These should also be designed to
      determine what predisposition(s), if any, might make the use of e-cigarettes more
      or less successful than that of other aids to smoking cessation. Moreover, e
      cigarettes might be a gateway drug for cigarette smoking; thus, no clear
      recommendation about their use can be made at present.

PMID- 24882624
TI  - A presynaptic role for PKA in synaptic tagging and memory.
AB  - Protein kinase A (PKA) and other signaling molecules are spatially restricted
      within neurons by A-kinase anchoring proteins (AKAPs). Although studies on
      compartmentalized PKA signaling have focused on postsynaptic mechanisms,
      presynaptically anchored PKA may contribute to synaptic plasticity and memory
      because PKA also regulates presynaptic transmitter release. Here, we examine this
      issue using genetic and pharmacological application of Ht31, a PKA anchoring
      disrupting peptide. At the hippocampal Schaffer collateral CA3-CA1 synapse, Ht31
      treatment elicits a rapid decay of synaptic responses to repetitive stimuli,
      indicating a fast depletion of the readily releasable pool of synaptic vesicles.
      The interaction between PKA and proteins involved in producing this pool of
      synaptic vesicles is supported by biochemical assays showing that synaptic
      vesicle protein 2 (SV2), Rim1, and SNAP25 are components of a complex that
      interacts with cAMP. Moreover, acute treatment with Ht31 reduces the levels of
      SV2. Finally, experiments with transgenic mouse lines, which express Ht31 in
      excitatory neurons at the Schaffer collateral CA3-CA1 synapse, highlight a
      requirement for presynaptically anchored PKA in pathway-specific synaptic tagging
      and long-term contextual fear memory. These results suggest that a
      presynaptically compartmentalized PKA is critical for synaptic plasticity and
      memory by regulating the readily releasable pool of synaptic vesicles. 

PMID- 24882627
TI  - The diagnosis and treatment of acute cough in adults.
AB  - BACKGROUND: Cough is the most common complaint for which patients visit their
      primary care physician, being present in about 8% of consultations. A profusion
      of new evidence has made it necessary to produce a comprehensively updated
      version of the guideline on cough of the German College of General Practitioners
      and Family Physicians (Deutsche Gesellschaft fur Allgemeinmedizin und
      Familienmedizin, DEGAM), which was last issued in 2008. METHOD: The
      interdisciplinary evidence and consensus based S3 guideline on cough of the DEGAM
      was updated on the basis of a systematic review of the relevant literature
      published from 2003 to July 2012 (MEDLINE, Cochrane Library, EMBASE, Web of
      Science). Evidence levels were assessed and consensus procedures were followed as
      prescribed by AWMF standards, with the participation of 7 medical societies.
      RESULTS: 182 publications were used to update the guideline, including 45
      systematic reviews (26 of which included a meta-analysis) and 17 randomized
      controlled trials (RCTs). 11 recommendations for acute cough were approved by
      consensus in a nominal group process. The history and physical examination are
      the basis of diagnostic evaluation. When the clinical diagnosis is that of an
      acute, uncomplicated bronchitis, no laboratory tests, sputum evaluation, or chest
      x-rays should be performed, and antibiotics should not be given. There is
      inadequate evidence for the efficacy of antitussive or expectorant drugs against
      acute cough. The state of the evidence for phytotherapeutic agents is
      heterogeneous. Persons with community-acquired pneumonia should receive empirical
      antibiotic treatment for 5 to 7 days; specific risk factors can influence the
      choice of drug to be used. It is recommended that laboratory tests should not be
      performed and neuraminidase inhibitors should not be given in the routine
      management of influenza. CONCLUSION: A specifically intended effect of these
      recommendations is to reduce the use of antibiotics to treat colds and acute
      bronchitis, for which they are not indicated. Further clinical trials of
      treatments for cough should be performed in order to extend the evidence base,
      which is now fragmentary.

PMID- 24882628
TI  - More patients in less time.

PMID- 24882629
TI  - Administering shortages.

PMID- 24882630
TI  - Turning children into psychiatric patients.

PMID- 24882631
TI  - In reply.

PMID- 24882632
TI  - Mitochondrial DNA plays an important role.

PMID- 24882633
TI  - In reply.

PMID- 24882634
TI  - Translational research--changing the landscape of pediatric nursing.

PMID- 24882637
TI  - Sex differences in neurological and psychiatric disorders.

PMID- 24882638
TI  - Kinetics of substrate inhibition of periplasmic nitrate reductase.
AB  - Periplasmic nitrate reductase catalyzes the reduction of nitrate into nitrite
      using a mononuclear molybdenum cofactor that has nearly the same structure in all
      enzymes of the DMSO reductase family. In previous electrochemical investigations,
      we found that the enzyme exists in several inactive states, some of which may
      have been previously isolated and mistaken for catalytic intermediates. In
      particular, the enzyme slowly and reversibly inactivates when exposed to high
      concentrations of nitrate. Here, we study the kinetics of substrate inhibition
      and its dependence on electrode potential and substrate concentration to learn
      about the properties of the active and inactive forms of the enzyme. We conclude
      that the substrate-inhibited enzyme never significantly accumulates in the EPR
      active Mo(+V) state. This conclusion is relevant to spectroscopic investigations
      where attempts are made to trap a Mo(+V) catalytic intermediate using high
      concentrations of nitrate. 

PMID- 24882640
TI  - Formation of a dihydroborole by catalytic isomerization of a divinylborane.
AB  - Diphenylamino(divinyl)borane (1a) adds two molar equivalents of Piers' borane
      [HB(C6F5)2] to give the expected double hydroboration product. In contrast
      diisopropylamino(divinyl)borane (1b) reacts cleanly already with one molar
      equivalent of HB(C6F5)2 to give the alpha-borylated tetrahydroborole derivative
      10 in good yield. Subsequent treatment of 10 with benzaldehyde proceeded by retro
      hydroboration to give the hydroboration product of the aldehyde plus the
      dihydroborole 3b. We were able to achieve the divinylborane to dihydroborole
      isomerization (1b to 3b) catalytically: treatment of
      diisopropylamino(divinyl)borane (1b) with 15 mol% of Piers' borane at elevated
      temperature gave (diisopropylamino)dihydroborole 3b in good yield.

PMID- 24882636
TI  - The role of hypothalamic estrogen receptors in metabolic regulation.
AB  - Estrogens regulate key features of metabolism, including food intake, body
      weight, energy expenditure, insulin sensitivity, leptin sensitivity, and body fat
      distribution. There are two 'classical' estrogen receptors (ERs): estrogen
      receptor alpha (ERS1) and estrogen receptor beta (ERS2). Human and murine data
      indicate ERS1 contributes to metabolic regulation more so than ESR2. For example,
      there are human inactivating mutations of ERS1 which recapitulate aspects of the
      metabolic syndrome in both men and women. Much of our understanding of the
      metabolic roles of ERS1 was initially uncovered in estrogen receptor alpha-null
      mice (ERS1(-/-)); these mice display aspects of the metabolic syndrome, including
      increased body weight, increased visceral fat deposition and dysregulated glucose
      intolerance. Recent data further implicate ERS1 in specific tissues and neuronal
      populations as being critical for regulating food intake, energy expenditure,
      body fat distribution and adipose tissue function. This review will focus
      predominantly on the role of hypothalamic ERs and their critical role in
      regulating all aspects of energy homeostasis and metabolism. 

PMID- 24882639
TI  - Imaging mass spectrometry reveals fiber-specific distribution of acetylcarnitine
      and contraction-induced carnitine dynamics in rat skeletal muscles.
AB  - Carnitine is well recognized as a key regulator of long-chain fatty acyl group
      translocation into the mitochondria. In addition, carnitine, as acetylcarnitine,
      acts as an acceptor of excess acetyl-CoA, a potent inhibitor of pyruvate
      dehydrogenase. Here, we provide a new methodology for accurate quantification of
      acetylcarnitine content and determination of its localization in skeletal
      muscles. We used matrix-assisted laser desorption/ionization imaging mass
      spectrometry (MALDI-IMS) to visualize acetylcarnitine distribution in rat
      skeletal muscles. MALDI-IMS and immunohistochemistry of serial cross-sections
      showed that acetylcarnitine was enriched in the slow-type muscle fibers. The
      concentration of ATP was lower in muscle regions with abundant acetylcarnitine,
      suggesting a relationship between acetylcarnitine and metabolic activity. Using
      our novel method, we detected an increase in acetylcarnitine content after muscle
      contraction. Importantly, this increase was not detected using traditional
      biochemical assays of homogenized muscles. We also demonstrated that acetylation
      of carnitine during muscle contraction was concomitant with glycogen depletion.
      Our methodology would be useful for the quantification of acetylcarnitine and its
      contraction-induced kinetics in skeletal muscles. 

PMID- 24882642
TI  - [New development of drug discovery research--novel molecular target and novel
      strategy].

PMID- 24882635
TI  - Estrogen-IGF-1 interactions in neuroprotection: ischemic stroke as a case study.
AB  - The steroid hormone 17b-estradiol and the peptide hormone insulin-like growth
      factor (IGF)-1 independently exert neuroprotective actions in neurologic diseases
      such as stroke. Only a few studies have directly addressed the interaction
      between the two hormone systems, however, there is a large literature that
      indicates potentially greater interactions between the 17b-estradiol and IGF-1
      systems. The present review focuses on key issues related to this interaction
      including IGF-1 and sex differences and common activation of second messenger
      systems. Using ischemic stroke as a case study, this review also focuses on
      independent and cooperative actions of estrogen and IGF-1 on neuroprotection,
      blood brain barrier integrity, angiogenesis, inflammation and post-stroke
      epilepsy. Finally, the review also focuses on the astrocyte, a key mediator of
      post stroke repair, as a local source of 17b-estradiol and IGF-1. This review
      thus highlights areas where significant new research is needed to clarify the
      interactions between these two neuroprotectants. 

PMID- 24882641
TI  - A novel perfusion-based method for cochlear implant electrode insertion.
AB  - A cochlear implant (CI) restores partial hearing to profoundly deaf individuals.
      CI electrodes are inserted manually in the cochlea and surgeons rely on tactile
      feedback from the implant to determine when to stop the insertion. This manual
      insertion method results in a large degree of variability in surgical outcomes
      and intra-cochlear trauma. Additionally, implants often span only the basal turn.
      In the present study we report on the development of a new method to assist CI
      electrode insertion. The design objectives are (1) an automated and standardized
      insertion technique across patients with (2) more apical insertion than is
      possible by the contemporary methods, while (3) minimizing insertion trauma. The
      method relies on a viscous fluid flow through the cochlea to carry the electrode
      array with it. A small cochleostomy (~100-150 um in diameter) is made in scala
      vestibuli (SV) and the round window (RW) membrane is opened. A flow of diluted
      Sodium Hyaluronate (also known as Hyaluronic Acid, (HA)) is set up from the RW to
      the SV opening using a perfusion pump that sets up a unidirectional flow. Once
      the flow is established an implant is dropped into the ongoing flow. Here we
      present a proof-of-concept study where we used this technique to insert silicone
      implants all the way to the cochlear apex in rats and gerbils. In light
      microscopic histology, the implantation occurred without cochlear trauma. To
      further assess the ototoxicity of the HA perfusion, we measured compound action
      potential (CAP) thresholds following the perfusion of HA, and found that the CAP
      thresholds were substantially elevated. Thus, at this point the method is
      promising, and requires further development to become clinically viable. 

PMID- 24882643
TI  - [Effect of repeated oral treatment with etoposide on the expression of intestinal
      P-glycoprotein and oral morphine analgesia].
AB  - Currently, the World Health Organization recommends oral administration of opioid
      analgesics for patients with cancer to treat cancer-related pain from the initial
      stage of treatment. Furthermore, many anticancer drugs have been newly-developed
      and approved as oral form. Because of this trend, the chances of drug-drug
      interactions between anticancer drugs and opioid analgesics during absorption
      process from the intestine are likely to increase. To investigate these possible
      drug-drug interactions, we have focused on intestinal P-glycoprotein (P-gp) which
      regulates the absorption of various substrate drugs administered orally.
      Previously, we have found that repeated oral treatment with etoposide (ETP), an
      anticancer drug, attenuates analgesia of oral morphine, a substrate drug for P
      gp, by increasing the expression and activity of intestinal P-gp. However, the
      mechanism by which ETP treatment increases the intestinal P-gp expression and
      decreases oral morphine analgesia remains unclear. RhoA, a small G-protein, and
      ROCK, an effector of RhoA, pathway has been attracted attention with regard to
      their involvement in the regulatory mechanism of the expression and activity of P
      gp. Interestingly, this pathway is activated in response to various signaling
      induced by some anticancer drugs. Furthermore, it has been reported that
      ezrin/radixin/moesin (ERM) play a key role in the plasma membrane localization of
      P-gp, and that RhoA/ROCK pathway regulates the activation process of ERM. This
      review article introduces the result of our previous research as well as recent
      findings on the involvement of ERM via activation of RhoA/ROCK in the increased
      expression of intestinal P-gp and decreased oral morphine analgesia induced by
      repeated oral treatment with ETP.

PMID- 24882644
TI  - [Anti-high mobility group box-1 antibody therapy for traumatic brain injury].
AB  - Traumatic brain injury (TBI) is one of the major causes of death and aftereffects
      in young individuals worldwide; however, efficient therapies for TBI are lacking
      at present. High mobility group box-1 (HMGB-1), which is recognized as a
      representative of danger-associated molecular patterns (DAMPs), plays an
      important role in triggering inflammatory responses in many types of diseases. We
      presented the involvement of HMGB-1 in TBI and evaluated the ability of
      intravenously administered neutralizing anti-HMGB-1 monoclonal antibody (mAb) to
      attenuate brain injury. Anti-HMGB-1 mAb may provide a novel and effective therapy
      for TBI by protecting against blood brain barrier disruption and reducing the
      inflammatory responses induced by HMGB-1.

PMID- 24882645
TI  - [Cardioprotective effect of the selective sigma-1 receptor agonist, SA4503].
AB  - We previously reported that the sigma-1 receptor is down-regulated in
      cardiomyocytes following heart failure in transverse aortic constriction (TAC)
      mice. In this review, we summarized the anti-hypertrophic action of selective
      sigma-1 receptor agonist, SA4503 in the hypertrophied cultured cardiomyocytes and
      discussed its possible mechanism of cardioprotection. Treatment with SA4503 (0.1
      1 MUM) dose-dependently inhibited hypertrophy in cultured cardiomyocytes induced
      by angiotensin II (Ang II). We also found that alpha1 receptor stimulation by
      phenylephrine (PE) promotes ATP production through IP3 receptor-mediated Ca(2+)
      mobilization into mitochondria in cultured cardiomyocytes. Interestingly, the PE
      induced ATP production was impaired after Ang II-induced hypertrophy and SA4503
      treatment largely restored PE-induced ATP production. The impaired PE-induced ATP
      production was associated with reduced mitochondrial size. The SA4503 treatment
      completely restored mitochondrial size concomitant with restored ATP production.
      These effects were blocked by sigma-1 receptor antagonist, NE-100 and sigma-1
      receptor siRNA. We also confirmed that chronic SA4503 administration also
      significantly attenuates myocardial hypertrophy and restores ATP production in
      transverse aortic constriction mice. Taken together, sigma-1 receptor stimulation
      with selective agonist SA4503 ameliorates cardiac hypertrophy and dysfunction by
      restoring both mitochondrial Ca(2+) mobilization and ATP production via sigma-1
      receptor stimulation. Sigma-1 receptor stimulation represents a new therapeutic
      strategy to rescue heart from hypertrophic dysfunction in heart failure.

PMID- 24882647
TI  - [Recent topics on development of nanomaterials and nano-safety science].

PMID- 24882646
TI  - [Drug development for cardiorenal disease based on oxidative stress control].
AB  - Oxidative stress is a key factor involved in the pathogenesis and progression of
      cardiovascular disease (CVD) and chronic kidney disease (CKD). Reactive oxygen
      species (ROS), produced as a result of redox reactions in various cells, have
      been recognized as key chemical mediators causing cellular damage and organ
      dysfunction in CVD and CKD. Nifedipine, a well-known calcium channel blocker, is
      extremely sensitive to light which gets converted to its nitroso analog,
      nitrosonifedipine (NO-NIF) in the presence of ultraviolet and visible light. The
      so formed NO-NIF blocks calcium channel quite weakly compared to that of
      nifedipine. However, we elucidated for the first time that NO-NIF is converted to
      NO-NIF radical which acquires extremely strong antioxidant property via reaction
      with unsaturated fatty acid or endothelial cells. We have already reported that
      NO-NIF reduces the cytotoxicity of cumene hydroperoxide, which hampers the
      integrity of cell membrane through oxidative stress, in endothelial cells.
      Additionally, we demonstrated that NO-NIF restored acetylcholine-responsive
      vascular relaxation and suppressed intercellular adhesion molecule-1 expression
      in the aorta of N(omega)-nitro-L-arginine methyl ester-treated rats, a model of
      vascular endothelial dysfunction. Recently, we reported that NO-NIF ameliorates
      angiotensin II-induced vascular remodeling via antioxidative effects in vivo and
      in vitro. These observations point towards the plausible, unique role of NO-NIF
      as a novel antioxidant which improves vascular dysfunction for overcoming CVD and
      CKD and the same has been highlighted in this review.

PMID- 24882648
TI  - [Cellular distribution and behavior of metallothionein in mammalian cells
      following exposure to silver nanoparticles and silver ions].
AB  - Silver nanoparticles (AgNPs) are commercially used mainly as antibacterial
      reagents in wound dressing and deodorant powders. However, the mechanisms
      underlying Ag toxicity in mammals are not fully understood. In the present study,
      we assessed cellular distribution and toxicity of AgNPs and AgNO3 in mouse
      macrophage cell line (J774.1) and those of AgNO3 in human bronchial epithelial
      cell line (BEAS-2B) focusing on behavior of metallothionein (MT). J774.1 cells
      were exposed to 0-100 MUg Ag/mL AgNPs or AgNO3 and BEAS-2B cells were exposed to
      0-100 MUM AgNO3 for 24 h. The cytotoxicity was assayed by a modified MTT method.
      The cellular concentration and distribution of Ag were evaluated by inductively
      coupled plasma-mass spectorometry (ICP-MS) and laser scanning microscopy.
      Distribution of Ag to MT and other proteins was determined using HPLC-ICP-MS.
      Most AgNPs were found in lysosomes in J774.1 at 3 h after post exposure. Ag was
      distributed to high molecular weight proteins in AgNPs-exposed cells, while most
      Ag was bound to MT in AgNO3-exposed cells. In AgNO3-exposed BEAS-2B cells
      cellular Ag concentration and Ag-bound MT (Ag-MT) were sharply increased up to 3
      h and then decreased. ROS production appeared to cause relocation of MT-bound Ag
      to mitochondria, which evoked inhibition of electron transport chain. AgNPs were
      sequestered by high-molecular weight proteins rather than MT, probably because
      they were taken up by lysosomes before induction of MT.

PMID- 24882649
TI  - [In vitro safety evaluation of nanomaterials--cellular response to metal oxide
      nanoparticles].
AB  - Although nanomaterials are already being used for various applications in the
      industry, the safety of nanomaterials has not yet been sufficiently elucidated.
      An in vitro cellular toxicological study using well-characterized nanomaterials
      is conducted for the evaluation of the biological effects of nanomaterials. In
      this study, the effects of copper oxide nanoparticles on the global gene
      expression of human lung epithelial A549 cells were analyzed, and the molecular
      responses of A549 cells to the toxicity of the copper oxide (CuO) nanoparticles
      were inferred. Furthermore, the cytotoxic effects of silicon dioxide (SiO2)
      nanoparticles and titanium dioxide (TiO2) nanoparticles coexisting with some
      metal salts in Chinese hamster lung fibroblast V79 cells were also examined, and
      SiO2 nanoparticles increased the cytotoxicity of some of the coexisting metal
      salts as a result. Finally, the importance of in vitro studies in the safety
      evaluation of nanomaterials was discussed.

PMID- 24882650
TI  - [Nano-safety science for sustainable nanotechnology].
AB  - Recently, it is concerned that nanomaterials induce undesirable biological
      responses (NanoTox) which is different from conventional materials attributed to
      their unique physicochemical properties in the world. However, for our enjoying
      the benefits of nanomateirals, it is most important not to regulate nanomaterials
      in the blind way but to assure the security of nanomaterials and support the
      development of nanomaterial industries. These are duty of our country to be
      advanced country, technology-oriented nation and intellectual property nation.
      From these viewpoints, we are engaged on not NanoTox study but Nano-safety
      science study. In this review, we will introduce our Nano-safety science study
      using mainly silica nanoparticle.

PMID- 24882651
TI  - [Involvement of ATP in radiation-induced bystander effect as a signaling
      molecule].
AB  - We previously reported that low doses (0.25-0.5 Gy) of gamma-rays induce
      intracellular antioxidant, radioresistant, DNA damage repair, and so on.
      Meanwhile, we have recently reported that ATP is released from the cells exposed
      to low-dose gamma-rays. Here, it was investigated whether or not gamma-radiation
      induced release of extracellular ATP contributes to various radiation effects, in
      paricular, focusing on the inductions of intracellular antioxidant and DNA damage
      repair. Irradiation with gamma-rays or exogenously added ATP increased expression
      of intracellular antioxidants such as thioredoxin and the increases were blocked
      by pretreatment with an ecto-nucleotidase in both cases. Moreover, release of ATP
      and autocrine/paracrine positive feedback through P2Y receptors serve to amplify
      the cellular repair response to radiation-induced DNA damage. To sum up, it would
      be suggested that ATP signaling is important for the effective induction of
      radiation stress response, such as protection of the body from the radiation and
      DNA damage repair. In addition, the possibility that this signaling is involved
      in the radiation resistance of cancer cells and beneficial effect on the organism
      of low-dose radiation and radiation adaptive response, would be further
      suggested.

PMID- 24882652
TI  - [Field survey of the anticancer drug contamination in the preparation
      environment. Usefulness of the 5-FU monitoring by the coupon method].
AB  - For medical professionals involved in cancer chemotherapy, occupational exposure
      of anticancer agents is considered a health risk. Education about the handling of
      anticancer drugs and proper use of protective equipment are important for
      reducing occupational exposure of anticancer drugs. Furthermore, monitoring of
      the contamination level of anticancer drugs is important for determining the
      propriety of anti-contamination methods. Cyclophosphamide (CPA) has been used as
      the standard drug of the contamination level; however, it is rarely detected
      because of the disparity between drug preparation frequency and consumption, and
      use of a closed system. Therefore, we chose 5-fluorouracil (5-FU) as the standard
      drug and attempted to monitor its contamination levels by sampling using drug
      absorption sheets (the coupon method). We measured contamination levels inside a
      biological safety cabinet (BSC) and at its lower floor, and at a preparation
      worktable, nurses' station worktable, its lower floor and floor of the hospital
      room in a chemotherapy room for outpatients of the Iwate Medical University
      Hospital for 3 time periods. 5-FU was detected in 72% of the coupons (n=108),
      while CPA was detected in only 7% of the coupons (n=108). Monitoring of 5-FU
      contamination levels by using the coupon method was considered useful for
      evaluating anti-contamination method and the contamination process.

PMID- 24882653
TI  - [Questionnaire survey about NSAIDs use in late pregnancy for pharmacists and
      physicians].
AB  - It has been reported the use of nonsteroid anti-inflammatory drugs (NSAIDs) in
      late pregnancy was associated with potentially fetal toxicity (contraction of
      fetal ductus areteriosus). According to the package inserts in Japan, many oral
      NSAIDs are contraindicated to women in late pregnancy, but several oral and
      topical NSAIDs with case reports of fetal toxicity are not. In the present study,
      a web-based questionnaire survey was conducted in pharmacists/physicians to
      determine their awareness of fetal toxicity caused by NSAIDs, as well as their
      attitudes regarding the use of NSAIDs in late pregnancy. Responses were obtained
      from 427 pharmacists, 22 obstetricians, and 160 non-obstetric physicians. Of the
      non-obstetric respondents, more than 40% had no knowledge of fetal ductus
      arteriosus contraction caused by oral ibuprofen, and most of them were not aware
      of the relevant warning statement on the package insert. In contrast, these were
      familiar to nearly 100% of the obstetricians. As for ketoprofen tape, only 20-40%
      of the pharmacists/physicians were aware of the warning statement, and nearly all
      respondents did not confirm whether the patient was in late pregnancy. The
      majority of the respondents answered that oral ibuprofen, ketoprofen tape and
      NSAID-containing OTC drugs should not be used in late pregnancy after they knew
      the warning statements in late pregnancy. This survey suggests that the fetal
      toxicity of NSAIDs is not well recognized by pharmacists/physicians. It would be
      necessary to make it thoroughly known to them through such as enrichment of
      safety information on the package inserts, accompanying with the evidence.

PMID- 24882654
TI  - [Effects of the combination of angiotensin receptor blockers and thiazide
      diuretics on laboratory values (levels of serum potassium, sodium, and uric
      acid)].
AB  - The combination of angiotensin receptor blockers (ARB) and a thiazide diuretic
      (hereafter, ARB/diuretic) is expected to improve patient adherence and increase
      the therapeutic effects because of the lower number of pills that require to be
      administered. In addition, an ARB/diuretic combination alleviates hypokalemia
      that frequently develops in patients receiving thiazide diuretics. In this study,
      we used electronic medical records to investigate the laboratory values (serum
      levels of potassium, sodium, and uric acid) of 194 ambulatory and hospitalized
      patients at the Gifu Municipal Hospital who received ARB/diuretic combination
      therapy for the first time between February 2010 and September 2012. According to
      the grade of classification of low serum potassium and sodium levels, the serum
      potassium level in one patient was grade 3 and the serum sodium level in two
      patients was grade 3 after the initiation of ARB/diuretic combination therapy.
      After administration of ARB/diuretic combination therapy, two patients received
      potassium supplements because their serum potassium levels decreased below the
      reference value. Similarly, one patient received a sodium supplement because of a
      decrease in the sodium level below the reference value. Uric acid level increased
      above the reference value after administration of the ARB/diuretic combination
      therapy in one patient; thus, this patient received antihyperuricemic agents.
      Therefore, pharmacists must carefully monitor the serum levels of potassium,
      sodium, and uric acid, particularly in the first six months after the initiation
      of ARB/diuretic combination therapy.

PMID- 24882655
TI  - [Acid-neutralizing capacity of over-the-counter gastrointestinal medications].
AB  - There is little information regarding the acid-neutralizing capacity of over
      the-counter (OTC) gastrointestinal medicines. In this study, we assessed the acid
      neutralizing capacity of OTC and prescribed gastrointestinal drugs based on the
      Japanese Pharmacopoeia 16th Edition. The acid-neutralizing capacity of the OTC
      drugs was calculated using experimental results for the crude materials found in
      the prescribed drugs based on OTC antacid quantity. The measured acid
      neutralizing capacities of the OTC drugs agreed with the respective calculated
      values. These results indicate that the acid-neutralizing capacity of OTC drugs
      labeled as an antacid without information on their capacity can be estimated
      based on the quantity and capacity of the antacid components. 

PMID- 24882656
TI  - Doppler detection in Ama divers of Japan.
AB  - OBJECTIVE: Symptoms consistent with neurological decompression sickness (DCS) in
      commercial breath-hold (Ama) divers has been reported from a few districts of
      Japan. The aim of this study was to detect circulating intravascular bubbles
      after repetitive breath-hold diving in a local area where DCS has been reported
      in Ama divers. METHODS: The participants were 12 partially assisted (descent
      using weights) male Ama divers. The equipment (AQUALAB system) consisted of
      continuous-wave Doppler with a 5-MHz frequency, and the Doppler probe was placed
      in the precordial site with the ultrasonic wave directed into the pulmonary
      infundibulum. We carried out continuous monitoring for 10 minutes at the end of
      the series of repetitive dives, and the recordings were made on numerical tracks
      and graded in a blind manner by 2 experienced investigators, according to the
      Spencer Doppler code. RESULTS: Depths and number of dives were 8 to 20 m and 75
      to 131 times. Mean diving duration and surface interval were 64 +/- 12 seconds
      and 48 +/- 8 seconds, respectively (mean +/- SD). We detected the lowest grade of
      intravascular bubbles (Spencer's grade I) in an Ama diver whose mean surface
      interval was only 35.2 +/- 6.2 seconds. His mean descending, bottom, and
      ascending times were 10.4 +/- 1.6 seconds, 39.2 +/- 8 seconds, and 18.2 +/- 3.0
      seconds, respectively, over the course of 99 dives. CONCLUSIONS: Intravascular
      bubbles may be formed after repetitive breath-hold dives with short surface
      intervals or after a long breath-holding session in Ama divers. Symptoms
      consistent with neurological accidents in repetitive breath-hold diving may be
      caused in part by the intravascular presence of bubbles, indicating the need for
      safety procedures.

PMID- 24882657
TI  - In reply to 'Symptomatic hypotonic hyponatremia presenting at high altitude'.

PMID- 24882658
TI  - Atraumatic splenic rupture after coagulopathy owing to a snakebite.
AB  - Among the many complications that may follow envenomation by some species of
      venomous snakes, coagulopathy is common and well known. However, hemoperitoneum
      induced by coagulopathy after a snakebite is rare. Atraumatic spontaneous splenic
      rupture is also an uncommon and life-threatening condition. Here, we report a
      case of presumptive envenomation by Gloydius spp. that resulted in atraumatic
      splenic rupture as a probable manifestation of coagulopathy, which has not been
      previously reported. 

PMID- 24882659
TI  - The incidence of acute mountain sickness among passengers traveling across the
      Tibetan Plateau by train.

PMID- 24882660
TI  - Effects of surface compositional and structural heterogeneity on nanoparticle
      protein interactions: different protein configurations.
AB  - As nanoparticles (NPs) enter into biological systems, they are immediately
      exposed to a variety and concentration of proteins. The physicochemical
      interactions between proteins and NPs are influenced by the surface properties of
      the NPs. To identify the effects of NP surface heterogeneity, the interactions
      between bovine serum albumin (BSA) and gold NPs (AuNPs) with similar chemical
      composition but different surface structures were investigated. Different
      interaction modes and BSA conformations were studied by dynamic light scattering,
      circular dichroism spectroscopy, fluorescence quenching and isothermal titration
      calorimetry (ITC). Depending on the surface structure of AuNPs, BSA seems to
      adopt either a "side-on" or an "end-on" conformation on AuNPs. ITC demonstrated
      that the adsorption of BSA onto AuNPs with randomly distributed polar and
      nonpolar groups was primarily driven by electrostatic interaction, and all BSA
      were adsorbed in the same process. The adsorption of BSA onto AuNPs covered with
      alternating domains of polar and nonpolar groups was a combination of different
      interactions. Overall, the results of this study point to the potential for
      utilizing nanoscale manipulation of NP surfaces to control the resulting NP
      protein interactions. 

PMID- 24882662
TI  - How and when do expert emergency physicians generate and evaluate diagnostic
      hypotheses? A qualitative study using head-mounted video cued-recall interviews.
AB  - STUDY OBJECTIVE: The ability to make a diagnosis is a crucial skill in emergency
      medicine. Little is known about the way emergency physicians reach a diagnosis.
      This study aims to identify how and when, during the initial patient examination,
      emergency physicians generate and evaluate diagnostic hypotheses. METHODS: We
      carried out a qualitative research project based on semistructured interviews
      with emergency physicians. The interviews concerned management of an emergency
      situation during routine medical practice. They were associated with viewing the
      video recording of emergency situations filmed in an "own-point-of-view"
      perspective. RESULTS: The emergency physicians generated an average of 5
      diagnostic hypotheses. Most of these hypotheses were generated before meeting the
      patient or within the first 5 minutes of the meeting. The hypotheses were then
      rank ordered within the context of a verification procedure based on identifying
      key information. These tasks were usually accomplished without conscious effort.
      No hypothesis was completely confirmed or refuted until the results of
      investigations were available. CONCLUSION: The generation and rank ordering of
      diagnostic hypotheses is based on the activation of cognitive processes, enabling
      expert emergency physicians to process environmental information and link it to
      past experiences. The physicians seemed to strive to avoid the risk of error by
      remaining aware of the possibility of alternative hypotheses as long as they did
      not have the results of investigations. Understanding the diagnostic process used
      by emergency physicians provides interesting ideas for training residents in a
      specialty in which the prevalence of reasoning errors leading to incorrect
      diagnoses is high.

PMID- 24882663
TI  - Appendicitis: do clinical scores matter?

PMID- 24882664
TI  - Can Heimlich valves along with intercostal catheters be used to safely manage
      pneumothoraces for outpatients?

PMID- 24882665
TI  - Evaluation of acute appendicitis by pediatric emergency physician sonography.
AB  - STUDY OBJECTIVE: We investigate the accuracy of pediatric emergency physician
      sonography for acute appendicitis in children. METHODS: We prospectively enrolled
      children requiring surgical or radiology consultation for suspected acute
      appendicitis at an urban pediatric emergency department. Pediatric emergency
      physicians performed focused right lower-quadrant sonography after didactics and
      hands-on training with a structured scanning algorithm, including the graded
      compression technique. We compared their sonographic interpretations with
      clinical and radiologic findings, as well as clinical outcomes as defined by
      follow-up or pathologic findings. RESULTS: Thirteen pediatric emergency medicine
      sonographers performed 264 ultrasonographic studies, including 85 (32%) in
      children with pathology-verified appendicitis. Bedside sonography had a
      sensitivity of 85% (95% confidence interval [CI] 75% to 95%), specificity of 93%
      (95% CI 85% to 100%), positive likelihood ratio of 11.7 (95% CI 6.9 to 20), and
      negative likelihood ratio of 0.17 (95% CI 0.1 to 0.28). CONCLUSION: With focused
      ultrasonographic training, pediatric emergency physicians can diagnose acute
      appendicitis with substantial accuracy.

PMID- 24882666
TI  - Emergency departments provide complementary care: care that is accessible, care
      that is timely.

PMID- 24882668
TI  - A switched energy saving position controller for variable-pressure electro
      hydraulic servo systems.
AB  - The electro-hydraulic servo system (EHSS) demonstrates a relatively low level of
      efficiency compared to other available actuation methods. The objective of this
      paper is to increase this efficiency by introducing a variable supply pressure
      into the system and controlling this pressure during the task of position
      tracking. For this purpose, an EHSS structure with controllable supply pressure
      is proposed and its dynamic model is derived from the basic laws of physics. A
      switching control structure is then proposed to control both the supply pressure
      and the cylinder position at the same time, in a way that reduces the overall
      energy consumption of the system. The stability of the proposed switching control
      system is guaranteed by proof, and its performance is verified by experimental
      testing. 

PMID- 24882667
TI  - Priorities for emergency department syncope research.
AB  - STUDY OBJECTIVES: There is limited evidence to guide the emergency department
      (ED) evaluation and management of syncope. The First International Workshop on
      Syncope Risk Stratification in the Emergency Department identified key research
      questions and methodological standards essential to advancing the science of ED
      based syncope research. METHODS: We recruited a multinational panel of syncope
      experts. A preconference survey identified research priorities, which were
      refined during and after the conference through an iterative review process.
      RESULTS: There were 31 participants from 7 countries who represented 10 clinical
      and methodological specialties. High-priority research recommendations were
      organized around a conceptual model of ED decisionmaking for syncope, and they
      address definition, cohort selection, risk stratification, and management.
      CONCLUSION: We convened a multispecialty group of syncope experts to identify the
      most pressing knowledge gaps and defined a high-priority research agenda to
      improve the care of patients with syncope in the ED.

PMID- 24882669
TI  - Hinfinity filtering for a class of discrete-time singular Markovian jump systems
      with time-varying delays.
AB  - The problem of Hinfinity filtering for a class of discrete-time singular
      Markovian jump systems with time-varying delays is investigated in this paper.
      The transition probabilities under consideration are time-varying, i.e.,
      Markovian chain is nonhomogeneous. By using the Lyapunov functional approach and
      reciprocally convex technique, a less conservative delay-dependent bounded real
      lemma is developed in terms of linear matrix inequalities. Moreover, a sufficient
      condition for the existence of the desired filter which guarantees the stochastic
      admissibility and the Hinfinity performance index of the resulting filtering
      error system is presented. Numerical examples are employed to show the usefulness
      of the proposed results. 

PMID- 24882670
TI  - Systemic therapy for non-clear cell renal cell carcinomas: a systematic review
      and meta-analysis.
AB  - CONTEXT: Clinical data supporting the use of targeted agents for the treatment of
      metastatic renal cell carcinoma (RCC) are based predominantly on patients with
      clear cell histology. Little is known about the efficacy of these drugs in non
      clear cell variants. OBJECTIVE: To evaluate the efficacy of different clear cell
      RCC (ccRCC)-approved targeted agents among patients with non-ccRCC compared with
      ccRCC. EVIDENCE ACQUISITION: We conducted a systematic review of electronic
      databases to identify publications evaluating the outcomes of patients with non
      ccRCC treated with targeted agents approved for treatment of ccRCC. Patients with
      sarcomatoid variant RCC were excluded from the main analysis but were evaluated
      as an independent cohort. End points of interest were response rate, median
      progression-free survival (PFS), and median overall survival (OS). Where
      possible, data were pooled in a meta-analysis. For studies of unselected patients
      with RCC, the outcomes of patients with non-ccRCC histology were compared with
      ccRCC. In exploratory analyses, outcomes of non-ccRCC with nonapproved agents
      were assessed. EVIDENCE SYNTHESIS: A total of 49 studies comprising 7771 patients
      were included in the analysis. Of these, 1244 patients (16.0%) had non-ccRCC,
      6300 (83.1%) had ccRCC, and 227 (2.9%) had sarcomatoid tumours. The overall
      response rate for non-ccRCC with targeted agents was 10.5%. In studies directly
      comparing non-ccRCC and ccRCC, there were significantly lower response rates for
      non-ccRCC (odds ratio for response: 0.52; 95% confidence interval, 0.40-0.68;
      p<0.001). For non-ccRCC treated with targeted agents, median PFS and OS were 7.4
      and 13.4 mo, respectively; for patients with ccRCC, these were 10.5 mo and 15.7
      mo, respectively (p value for difference<0.001 for both parameters). CONCLUSIONS:
      Patients with non-clear cell renal cell carcinoma (non-ccRCC) have significantly
      lower response rates and poorer median progression-free survival and overall
      survival than those with ccRCC. The optimal treatment of patients with non-ccRCC
      remains unclear and warrants further study. PATIENT SUMMARY: Systemic treatments
      for patients with renal cell carcinoma (RCC) tend to be significantly less
      effective for non-clear cell RCC, with lower response rates and worse progression
      free survival and overall survival when compared with clear cell RCC. Optimal
      therapy remains unclear and warrants further study.

PMID- 24882671
TI  - Reply to Michael Froehner, Manfred P. Wirth's letter to the editor re: Jim C. Hu,
      Giorgio Gandaglia, Pierre I. Karakiewicz, et al. Comparative effectiveness of
      robot-assisted versus open radical prostatectomy cancer control. Eur Urol
      2014;66:666-72.

PMID- 24882672
TI  - More extensive pelvic lymph node dissection improves survival in patients with
      node-positive prostate cancer.
AB  - BACKGROUND: The role of extended pelvic lymph node dissection (ePLND) in treating
      prostate cancer (PCa) patients with lymph node invasion (LNI) remains
      controversial. OBJECTIVE: The relationship between the number of removed lymph
      nodes (RLNs) and cancer-specific mortality (CSM) was tested in patients with LNI.
      DESIGN, SETTING, AND PARTICIPANTS: We examined data of 315 pN1 PCa patients
      treated with radical prostatectomy (RP) and anatomically ePLND between 2000 and
      2012 at one tertiary care centre. All patients received adjuvant hormonal therapy
      with or without adjuvant radiotherapy (aRT). OUTCOME MEASUREMENTS AND STATISTICAL
      ANALYSIS: Univariable and multivariable Cox regression analyses tested the
      relationship between RLN number and CSM rate, after adjusting to all available
      covariates. Survival estimates were based on the multivariable model; patients
      were stratified according to RLN number using points of maximum separation.
      RESULTS AND LIMITATIONS: The average number of RLNs was 20.8 (median: 19;
      interquartile range: 14-25). Mean and median follow-up were 63.1 and 54 mo,
      respectively. At 10-yr, the CSM-free survival rate was 74.7%, 85.9%, 92.4%,
      96.0%, and 97.9% for patients with 8, 17, 26, 36, and 45 RLNs, respectively. By
      multivariable analyses, the number of RLNs independently predicted lower CSM rate
      (hazard ratio [HR]: 0.93; p=0.02). Other predictors of CSM were Gleason score 8
      10 (HR: 3.3), number of positive nodes (HR: 1.2), and aRT treatment (HR: 0.26;
      all p <= 0.006). The study is limited by its retrospective nature. CONCLUSIONS:
      In PCa patients with LNI, the removal of a higher number of LNs during RP was
      associated with improvement in cancer-specific survival rate. This implies that
      ePLND should be considered in all patients with a significant preoperative risk
      of harbouring LNI. PATIENT SUMMARY: We found that removing more lymph nodes
      during prostate cancer surgery can significantly improve cancer-specific survival
      in patients with lymph node invasion.

PMID- 24882674
TI  - Preparation and characterization of multi stimuli-responsive photoluminescent
      nanocomposites of graphene quantum dots with hyperbranched polyethylenimine
      derivatives.
AB  - Oxidized graphene sheets (OGS) were treated with a hyperbranched polyethylenimine
      (PEI) under hydrothermal conditions to generate nanocomposites of graphene
      quantum dots (GQDs) functionalized with PEI (GQD-PEIs). The influence of the
      reaction temperature and the PEI/OGS feed ratio on the photoluminescence
      properties of the GQD-PEIs was studied. The obtained GQD-PEIs were characterized
      by TEM, dynamic light scattering, elemental analysis, FTIR, zeta potential
      measurements and (1)H NMR spectroscopy, from which their structural information
      was inferred. Subsequently, isobutyric amide (IBAm) groups were attached to the
      GQD-PEIs through the amidation reaction of isobutyric anhydride with the PEI
      moieties, which resulted in GQD-PEI-IBAm nanocomposites. GQD-PEI-IBAm was not
      only thermoresponsive, but also responded to other stimuli, including inorganic
      salts, pH, and loaded organic guests. The cloud point temperature (Tcp) of
      aqueous solutions of GQD-PEI-IBAm could be modulated through changing the number
      of IBAm units in GQD-PEI-IBAm, by varying the type and concentration of the
      inorganic salts and loaded organic guests, or by varying the pH. All the obtained
      GQD-PEI-IBAm nanocomposites were photoluminescent, and their maximum emission
      wavelengths were not influenced by outside stimuli. Their emission intensities
      were influenced a little or negligibly by pH, traditional salting-out anions (Cl(
      ) and SO4(2-)), and the relatively polar aspirin guest. However, the traditional
      salting-in I(-) anion and the more hydrophobic 1-pyrenebutyric acid (PBA) guest
      could effectively quench their fluorescence. 2D NOESY (1)H NMR spectra verified
      that GQD-PEI-IBAm accommodated the relatively polar aspirin guest using the PEI
      IBAm shell, but adsorbed the relatively hydrophobic PBA guest through the
      nanographene core. The release rate of the guest encapsulated by the
      thermoresponsive GQD is different below and above Tcp. 

PMID- 24882675
TI  - Design, synthesis and biological evaluation of novel 6,7-disubstituted-4
      phenoxyquinoline derivatives bearing 4-oxo-3,4-dihydrophthalazine-1-carboxamide
      moieties as c-Met kinase inhibitors.
AB  - A series of 6,7-disubstituted-4-phenoxyquinoline derivatives bearing 4-oxo-3,4
      dihydrophthalazine-1-carboxamide moieties were designed, synthesized and
      evaluated for their c-Met kinase inhibition and cytotoxicity against H460, MKN
      45, HT-29 and MDA-MB-231 cancer cell lines in vitro. Most compounds displayed
      good to excellent potency against four tested cancer cell lines as compared with
      foretinib. The SAR analyses indicated that compounds with halogen groups,
      especially fluoro groups at 4-position on the phenyl ring (moiety B) were more
      effective than those with nitro groups or methoxy groups. In this study, a
      promising compound 33 (c-Met IC50=1.63nM) was identified, which showed the most
      potent antitumor activities with IC50 values of 0.055MUM, 0.071MUM, 0.13MUM, and
      0.43MUM against H460, MKN-45, HT-29 and MDA-MB-231 cell lines, respectively. 

PMID- 24882673
TI  - Molecular characterization of enzalutamide-treated bone metastatic castration
      resistant prostate cancer.
AB  - BACKGROUND: Enzalutamide is a novel antiandrogen with proven efficacy in
      metastatic castration-resistant prostate cancer (mCRPC). OBJECTIVE: To evaluate
      enzalutamide's effects on cancer and on androgens in blood and bone marrow, and
      associate these with clinical observations. DESIGN, SETTING, AND PARTICIPANTS: In
      this prospective phase 2 study, 60 patients with bone mCRPC received enzalutamide
      160mg orally daily and had transilial bone marrow biopsies before treatment and
      at 8 wk of treatment. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Androgen
      signaling components (androgen receptor [AR], AR splice variant 7 (ARV7), v-ets
      avian erythroblastosis virus E26 oncogene homolog [ERG], cytochrome P450, family
      17, subfamily A, polypeptide 1 [CYP17]) and molecules implicated in mCRPC
      progression (phospho-Met, phospho-Src, glucocorticoid receptor, Ki67) were
      assessed by immunohistochemistry; testosterone, cortisol, and androstenedione
      concentrations were assessed by liquid chromatography-tandem mass spectrometry;
      AR copy number was assessed by real-time polymerase chain reaction. Descriptive
      statistics were applied. RESULTS AND LIMITATIONS: Median time to treatment
      discontinuation was 22 wk (95% confidence interval, 19.9-29.6). Twenty-two (37%)
      patients exhibited primary resistance to enzalutamide, discontinuing treatment
      within 4 mo. Maximal prostate-specific antigen (PSA) decline >= 50% and >= 90%
      occurred in 27 (45%) and 13 (22%) patients, respectively. Following 8 wk of
      treatment, bone marrow and circulating testosterone levels increased.
      Pretreatment tumor nuclear AR overexpression (> 75%) and CYP17 (> 10%) expression
      were associated with benefit (p = 0.018). AR subcellular localization shift from
      the nucleus was confirmed in eight paired samples (with PSA decline) of 23
      evaluable paired samples. Presence of an ARV7 variant was associated with primary
      resistance to enzalutamide (p = 0.018). Limited patient numbers warrant further
      validation. CONCLUSIONS: The observed subcellular shift of AR from the nucleus
      and increased testosterone concentration provide the first evidence in humans
      that enzalutamide suppresses AR signaling while inducing an adaptive feedback.
      Persistent androgen signaling in mCRPC was predictive of benefit and ARV7 was
      associated with primary resistance. PATIENT SUMMARY: We report a first bone
      biopsy study in metastatic prostate cancer in humans that searched for predictors
      of outcome of enzalutamide therapy. Benefit is linked to a pretreatment androgen
      signaling signature. TRIAL REGISTRATION: ClinicalTrials.gov identifier
      NCT01091103.

PMID- 24882676
TI  - Novel 3-arylfuran-2(5H)-one-fluoroquinolone hybrid: design, synthesis and
      evaluation as antibacterial agent.
AB  - 3-Arylfuran-2(5H)-one, a novel antibacterial pharmacophore targeting tyrosyl-tRNA
      synthetase (TyrRS), was hybridized with the clinically used fluoroquinolones to
      give a series of novel multi-target antimicrobial agents. Thus, twenty seven 3
      arylfuran-2(5H)-one-fluoroquinolone hybrids were synthesized and evaluated for
      their antimicrobial activities. Some of the hybrids exhibited merits from both
      parents, displaying a broad spectrum of activity against resistant strains
      including both Gram-negative and Gram-positive bacteria. The most potent compound
      (11) in antibacterial assay shows MIC50 of 0.11MUg/mL against Multiple drug
      resistant Escherichia coli, being about 51-fold more potent than ciprofloxacin.
      The enzyme assays reveal that 11 is a potent multi-target inhibitor with IC50 of
      1.15+/-0.07MUM against DNA gyrase and 0.12+/-0.04MUM against TyrRS, respectively.
      Its excellent inhibitory activities against isolated enzymes and intact cells
      strongly suggest that 11 deserves to further research as a novel antibiotic. 

PMID- 24882677
TI  - Recent advances in antithrombotic treatment for acute coronary syndromes.
AB  - Anti-thrombotic drugs constitute the cornerstone of therapy in the management of
      acute coronary syndromes (ACS) and for patients undergoing percutaneous coronary
      intervention. Anti-thrombotic therapy during percutaneous coronary intervention
      for ACS has evolved substantially over the past 15 years. In the original 1996
      ACC/AHA guidelines for the management of acute myocardial infarction (MI), only
      one antiplatelet agent (aspirin) and one anticoagulant (unfractionated heparin)
      were recommended as class I therapies. Much has since changed and the
      contemporary therapeutic armoury for the treatment of ACS reflects the
      pharmacological advances that have taken place. Recent developments in the
      medical management of ACS have been based around developing drugs with more
      predictable efficacy and at known drug targets. However there has also been
      considerable development of novel agents. New pharmacotherapies for ACS reflect
      efforts to improve efficacy and minimize complications by increasing target
      specificity and reducing inter-individual variation in therapeutic response.

PMID- 24882678
TI  - Functional MRI of pain application in youth who engaged in repetitive non
      suicidal self-injury vs. psychiatric controls.
AB  - Non-suicidal self-injury (NSSI) is increasingly common in young psychiatric
      patients. It is unclear why pain, which should be aversive, becomes reinforcing
      in this context. We hypothesized that pain- and/or reward-processing
      neurocircuitry would be abnormal in NSSI patients compared with non-NSSI
      patients. Using functional magnetic resonance imaging, we administered a
      painfully cold and comparison cool stimulus under two conditions: self
      administered and experimenter-administered (as a control). Participants comprised
      13 NSSI patients and 15 non-NSSI control patients, who were matched for sex, age,
      medications, symptoms, and diagnoses. Whole-brain analyses of main effects, as
      well as correlational analyses with subjective pain and "relief" (suggesting
      reward), were performed. Significant main effects of group showed greater blood
      oxygenation level-dependent (BOLD) response for NSSI than controls in right
      midbrain/pons; culmen; amygdala; and parahippocampal, inferior frontal and
      superior temporal gyri; as well as orbital frontal cortex (OFC). The correlation
      between BOLD signal and "relief" was greater in NSSI patients in areas associated
      with reward/pain and addiction including thalamus, dorsal striatum and anterior
      precuneus. Post hoc analysis showed reduced functional connectivity between right
      OFC and anterior cingulate cortex in NSSI youth, implying possible deficits in
      the neuroregulation of emotional behavior. These findings help inform how pain is
      associated with reward for NSSI patients but not for non-NSSI patients. 

PMID- 24882680
TI  - Crown heights in the permanent teeth of 45,X and 45,X/46,XX females.
AB  - OBJECTIVE: Previous results regarding human sex chromosome aneuploidies have
      shown that the X and Y chromosomes affect tooth size and morphology. This study
      looked for the effect of sex chromosome deficiency on permanent tooth crown
      heights. MATERIALS AND METHODS: The material, from the Finnish KVANTTI Research
      Project, consisted of 97 45,X females and 15 45,X/46,XX females. The controls
      were 32 sisters and 28 mothers of the 45,X females, eight sisters and two mothers
      of the 45,X/46,XX females and 35 female population controls. Crown heights of all
      the available teeth except third molars on both sides of the jaws were measured
      from panoramic radiographs with a digital calliper according to the defined
      procedure. RESULTS: The tooth crown heights were significantly smaller in the
      45,X females than in the female population controls, except for the incisors and
      one canine in the maxilla, whereas the tooth crown heights of the 45,X/46,XX
      females were close to those of the normal control females. The differences
      between the 45,X and 45,X/46,XX females were statistically significant, excluding
      the upper incisor area and a few teeth in the mandible. CONCLUSIONS: The effect
      of the sex chromosome deficiency on permanent tooth crown height is due to the
      magnitude of lacking sex chromosome material. The present results regarding the
      45,X females are parallel to previous findings in Turner patients regarding
      reduced mesiodistal and labiolingual dimensions and tooth crown heights in the
      permanent dentition.

PMID- 24882679
TI  - Morphometric hemispheric asymmetry of orbitofrontal cortex in women with
      borderline personality disorder: a multi-parameter approach.
AB  - Functional imaging studies have implicated the orbitofrontal cortex (OFC) in the
      pathophysiology of borderline personality disorder (BPD). To date, however,
      volume-based magnetic resonance imaging (MRI) studies have yielded mixed results.
      We used a surface-based processing approach that allowed us to measure five
      morphometric cortical features of the OFC, including volumetric (cortical
      thickness and surface area) and geometric (mean curvature, depth of sulcus, and
      metric distortion - three indicators of cortical folding) parameters.
      Participants comprised 25 female BPD patients with no other current psychiatric
      comorbidity and 25 age- and gender-matched healthy controls who received
      structural MRI scans. Images were processed using the Freesurfer package. All BPD
      patients had a history of comorbid psychiatric disorder(s) and were currently on
      medications. Compared with controls, the BPD group showed reduced cortical
      thickness, surface area, mean curvature, depth of sulcus, and metric distortion
      in the right medial OFC. In the left medial OFC, the BPD group had reduced
      cortical thickness and mean curvature, but increased metric distortion. This
      study confirmed the utility of surface-based analysis in the study of BPD
      cortical structures. In addition, we observed extensive structural abnormalities
      in the medial OFC of female subjects with BPD, findings that were most pronounced
      in the right OFC, with preliminary data suggesting hemispheric asymmetry. 

PMID- 24882681
TI  - The impact of job accommodations on employment outcomes among individuals with
      psychiatric disabilities.
AB  - OBJECTIVE: This study aimed to fill a gap in the literature on effectiveness of
      employment accommodations by comparing employment outcomes for individuals with
      psychiatric disabilities who received or did not receive accommodations, with
      models informed by a conceptual approach blending static labor supply theory,
      Sen's capability approach, and the International Classification of Functioning.
      METHODS: Data for the study came from a longitudinal, four-year eight-state
      multisite demonstration project funded by the U.S. Department of Health and Human
      Services' Substance Abuse and Mental Health Services Administration. All
      participants had been recruited from clinical populations receiving outpatient
      psychiatric services. The effects of job accommodations on hours worked were
      assessed with generalized linear modeling (N=1,538). The effects of job
      accommodations on duration of employment were assessed with a parametric duration
      model analysis (N=1,040) that incorporated multiple spells of employment among
      individuals over the study period. RESULTS: Controlling for covariates suggested
      by the conceptual model, analyses showed that individuals who reported job
      accommodations on average worked 7.68 more hours per month and those who reported
      receiving accommodations worked 31% longer, with each job accommodation reported
      decreasing the risk of job termination by nearly 13%. CONCLUSIONS: Results
      demonstrate that job accommodations show potential to improve employment outcomes
      for individuals with psychiatric disabilities receiving supported employment
      services, indicating that job accommodations should be stressed in policy and
      continuing education efforts for program staff and clients.

PMID- 24882682
TI  - Innate cytokine profiling of bovine alveolar macrophages reveals commonalities
      and divergence in the response to Mycobacterium bovis and Mycobacterium
      tuberculosis infection.
AB  - Despite sharing >99.9% genome sequence similarity at the nucleotide level,
      Mycobacterium tuberculosis and Mycobacterium bovis-the causative agents of human
      and bovine tuberculosis, respectively-exhibit distinct host preferences. M. bovis
      can cause disease in both cattle and humans yet rarely transmits between immuno
      competent human hosts, while M. tuberculosis is a highly successful pathogen of
      humans that does not sustain in animal populations. Based on the key role played
      by alveolar macrophages during mycobacterial infection, we hypothesised that the
      immunological and pathological differences observed in cattle infected with
      virulent M. bovis and M. tuberculosis may have a basis in innate immune
      mechanisms; these differences, in turn, would be reflected at the macrophage mRNA
      and protein level. To investigate this, we have analysed the transcriptional
      profile of innate immune genes in bovine alveolar macrophages following 24 and 48
      h infection with the genome-sequenced strains, M. bovis AF2122/97 and M.
      tuberculosis H37Rv. A bespoke multiplex ELISA was also used to quantify
      corresponding cytokine secretion in supernatants from the same infected alveolar
      macrophages. All cytokines showed similar significant patterns of expression
      (i.e., up- or down-regulation) at both the mRNA and protein levels in infected
      macrophages relative to parallel non-infected controls at the two time points (P
      <= 0.05). However, significant upregulation and downregulation of several innate
      immune genes-including TLR2, FOS, PIK3IP1, CCL4, IL1B, IL6 and TNF-and the CCL-4
      protein was observed in the M. bovis-infected macrophages relative to the M.
      tuberculosis-infected macrophages 48 h post-infection (P <= 0.05). These results
      support the hypothesis that the divergent virulence of M. bovis and M.
      tuberculosis in cattle has a basis in innate immune mechanisms, which may
      contribute to host preference within the M. tuberculosis complex of strains.

PMID- 24882684
TI  - Telomere repeats and macronuclear DNA organization in the soil ciliate Kahliella
      matisi (Ciliophora, Hypotricha).
AB  - To better understand the structure of macronuclear chromosomes in ciliates, the
      organization of macronuclear DNA was investigated in the hypotrich Kahliella
      matisi. Total DNA of K. matisi separated by agarose gel electrophoresis showed
      continuous smear ranging in size from ~500bp to ~15kb. This fragmentation was
      found to be due to the presence of gene-sized macronuclear chromosomes. The
      sequence analysis of four randomly cloned macronuclear chromosomes showed that K.
      matisi telomeres consist of 5'-dC4A4-3' repeats and carry one or two open reading
      frames. The transcription unit was found to be flanked with non-coding AT rich 5'
      leader and 3' trailer. No consensus transcription-regulatory sequences were
      identified in 5' leader and only one of analyzed gene-sized chromosomes showed
      the presence of conserved poly(A) addition signal sequence in 3' trailer. All
      ORFs showed highest relatedness to Oxytricha trifallax macronuclear chromosomes
      with conserved exon/intron structure. Sequence comparisons indicate that
      macronuclear chromosome organization is at least partially conserved in ciliates.

PMID- 24882683
TI  - Morphologic and molecular description of Metopus fuscus Kahl from North America
      and new rDNA sequences from seven metopids (Armophorea, Metopidae).
AB  - Most species in the large ciliate genus Metopus Claparede & Lachmann, 1858 lack
      detailed descriptions based on modern morphologic and molecular methods. This
      lack of data for the vast majority of species hampers application of a
      morphospecies approach to the taxonomy of Metopus and other armophorids. In this
      report we redescribe the large species, Metopus fuscusKahl, 1927 based on in vivo
      observation, silver impregnation, scanning electron microscopy, and single-cell
      18S rDNA sequencing of a freshwater North American (Idaho) population. Metopus
      fuscus invariably has a perinuclear envelope of endosymbiotic bacteria not found
      in other species. Unlike the original description of a single row of coarse
      granules between ciliary rows, the Idaho population has five loose rows of small
      interkinetal granules. We discuss the possible importance of this character in
      metopids. We also provide a phylogenetic analysis including seven other new
      metopid 18S rDNA sequences: Brachonella spiralis, B. galeata, Metopus laminarius,
      M. setosus, M. striatus, M. violaceus, Palmarella lata. Metopus fuscus and M.
      setosus form a fully supported clade, challenging previous morphospecies
      groupings. We discuss some ambiguities of armophorid morphologic terminology in
      the earlier literature. Our phylogenetic analysis of Idaho metopids indicates
      that the genera Metopus and Brachonella are both nonmonophyletic. 

PMID- 24882685
TI  - The first European stand of Paramecium sonneborni (P. aurelia complex), a species
      known only from North America (Texas, USA).
AB  - P. aurelia is currently defined as a complex of 15 sibling species including 14
      species designated by Sonneborn (1975) and one, P. sonneborni, by Aufderheide et
      al. (1983). The latter was known from only one stand (Texas, USA). The main
      reason for the present study was a new stand of Paramecium in Cyprus, with
      strains recognized as P. sonneborni based on the results of strain crosses,
      cytological slides, and molecular analyses of three loci (ITS1-5.8S-ITS2-5'LSU
      rDNA, COI, CytB). The new stand of P. sonneborni in Europe shows that the
      species, previously considered endemic, may have a wider range. This demonstrates
      the impact of under-sampling on the knowledge of the biogeography of microbial
      eukaryotes. Phylogenetic trees based on all the studied fragments revealed that
      P. sonneborni forms a separate cluster that is closer to P. jenningsi and P.
      schewiakoffi than to the other members of the P. aurelia complex. 

PMID- 24882686
TI  - Further investigations on the polypeptides and reconstitution of prasinophycean
      ejectisomes.
AB  - Ejectisome fragments were isolated from the prasinophyte Pyramimonas grossii and
      subjected to different treatments, i.e. Percoll density gradient centrifugation,
      incubation at pH 2.5 or at pH 10.8, or incubation in 6M guanidine hydrochloride.
      Sodium dodecyl sulfate polyacrylamide gel electrophoresis revealed that Percoll
      density gradient centrifugation did not improve the purity of the ejectisome
      fragment-enriched fractions. The ejectisome fragments withstood pH 2.5 and pH
      10.8 treatment, and no loosely bound polypeptides became detached. The
      disintegration of ejectisome fragments was achieved in 6M guanidine
      hydrochloride, and reassembly into filamentous, ejectisome-like structures
      occurred after dialysis against distilled water. Fractions enriched either in
      ejectisome fragments or in reconstituted ejectisome-like structures were
      dominated by three polypeptides with relative molecular weights of approximately
      12.5-19kDa and two additional polypeptides of 23 and 26kDa. A polyclonal
      antiserum directed against an ejectisome fragment-enriched fraction weakly cross
      reacted with these polypeptides, and no significant immuno-labelling of
      ejectisome fragments was registered. A positive immuno-label was achieved using
      immunoglobulin (IgG) fractions which were gained by selectively incubating
      nitrocellulose stripes of these polypeptides with the antiserum. 

PMID- 24882687
TI  - Elusive reproducibility.
AB  - Reproducibility remains a mirage for many biomedical studies because inherent
      experimental uncertainties generate idiosyncratic outcomes. The authentication
      and error rates of primary empirical data are often elusive, while multifactorial
      confounders beset experimental setups. Substantive methodological remedies are
      difficult to conceive, signifying that many biomedical studies yield more or less
      plausible results, depending on the attending uncertainties. Real life
      applications of those results remain problematic, with important exceptions for
      counterfactual field validations of strong experimental signals, notably for some
      vaccines and drugs, and for certain safety and occupational measures. It is
      argued that industrial, commercial and public policies and regulations could not
      ethically rely on unreliable biomedical results; rather, they should be
      rationally grounded on transparent cost-benefit tradeoffs. 

PMID- 24882688
TI  - Amethystin, the coloring principle of Stentor amethystinus.
AB  - Among the ciliates, Stentor amethystinus stands out for its conspicuous red
      violet color compared to its blue- and red-colored relatives Stentor coeruleus
      and Blepharisma japonicum. Rich blooms in German lakes allowed us to collect
      sufficient organisms to isolate the pigments and elucidate the structure of the
      main component amethystin (4) by spectroscopic methods as a carboxy derivative of
      blepharismin. Depending on conditions, the carboxy group appears as an orthoester
      or as a mixture of the orthoester and small amounts of a hydroxylactone.
      Derivatives of both isomeric forms were obtained by acetylation and methylation
      supporting the proposed structures. On reaction of amethystin with base in the
      presence of oxygen, oxyamethystin and, under vigorous conditions, p
      hydroxybenzoic acid were formed. In addition to 4, two homologues, an isomer of
      amethystin, and stentorin F (1b) were identified in the primary extract. Further,
      a biosynthetic scheme is proposed linking stentorin, blepharismin, and amethystin
      type compounds to the hypothetical protostentorin as a common intermediate. 

PMID- 24882689
TI  - The beta-catenin E3 ubiquitin ligase SIAH-1 is regulated by CSN5/JAB1 in CRC
      cells.
AB  - COP9 signalosome subunit 5 (CSN5) plays a decisive role in cellular processes
      such as cell cycle regulation and apoptosis via promoting protein degradation,
      gene transcription, and nuclear export. CSN5 regulates cullin-RING-E3 ligase
      (CRL) activity through its deNEDDylase function. It is overexpressed in several
      tumor entities, but its role in colorectal cancer (CRC) is poorly understood.
      Wnt/beta-catenin signaling is aberrant in most CRC cells, resulting in increased
      levels of oncogenic beta-catenin and thus tumor progression. Under physiological
      conditions, beta-catenin levels are tightly regulated by continuous proteasomal
      degradation. We recently showed that knockdown of CSN5 in model and CRC cells
      results in decreased (phospho)-beta-catenin levels. Reduced beta-catenin levels
      were associated with an attenuated proliferation rate of different CRC cell types
      after CSN5 knockdown. The canonical Wnt pathway involves degradation of beta
      catenin by a beta-TrCP1-containing E3 ligase, but is mostly non-functional in CRC
      cells. We thus hypothesized that alternative beta-catenin degradation mediated by
      SIAH-1 (seven in absentia homolog-1), is responsible for the effect of CSN5 on
      beta-catenin signaling in CRC cells. We found that SIAH-1 plays an essential role
      in beta-catenin degradation in HCT116 CRC cells and that CSN5 affects beta
      catenin target gene expression in these cells. Of note, CSN5 affected SIAH-1 mRNA
      and SIAH-1 protein levels. Moreover, beta-catenin and SIAH-1 form protein
      complexes with CSN5 in HCT116 cells. Lastly, we demonstrate that CSN5 promotes
      SIAH-1 degradation in HCT116 and SW480 cells and that this is associated with its
      deNEDDylase activity. In conclusion, we have identified a CSN5/beta-catenin/SIAH
      1 interaction network that might control beta-catenin degradation in CRC cells.

PMID- 24882690
TI  - Apremilast is a selective PDE4 inhibitor with regulatory effects on innate
      immunity.
AB  - Apremilast, an oral small molecule inhibitor of phosphodiesterase 4 (PDE4), is in
      development for chronic inflammatory disorders, and has shown efficacy in
      psoriasis, psoriatic arthropathies, and Behcet's syndrome. In March 2014, the US
      Food and Drug Administration approved apremilast for the treatment of adult
      patients with active psoriatic arthritis. The properties of apremilast were
      evaluated to determine its specificity, effects on intracellular signaling, gene
      and protein expression, and in vivo pharmacology using models of innate and
      adaptive immunity. Apremilast inhibited PDE4 isoforms from all four sub-families
      (A1A, B1, B2, C1, and D2), with IC50 values in the range of 10 to 100 nM.
      Apremilast did not significantly inhibit other PDEs, kinases, enzymes, or
      receptors. While both apremilast and thalidomide share a phthalimide ring
      structure, apremilast lacks the glutarimide ring and thus fails to bind to
      cereblon, the target of thalidomide action. In monocytes and T cells, apremilast
      elevated intracellular cAMP and induced phosphorylation of the protein kinase A
      substrates CREB and activating transcription factor-1 while inhibiting NF-kappaB
      transcriptional activity, resulting in both up- and down-regulation of several
      genes induced via TLR4. Apremilast reduced interferon-alpha production by
      plasmacytoid dendritic cells and inhibited T-cell cytokine production, but had
      little effect on B-cell immunoglobulin secretion. In a transgenic T-cell and B
      cell transfer murine model, apremilast (5mg/kg/day p.o.) did not affect clonal
      expansion of either T or B cells and had little or no effect on their expression
      of activation markers. The effect of apremilast on innate immunity was tested in
      the ferret lung neutrophilia model, which allows monitoring of the known PDE4
      inhibitor gastrointestinal side effects (nausea and vomiting). Apremilast
      significantly inhibited lung neutrophilia at 1mg/kg, but did not induce
      significant emetic reflexes at doses <30 mg/kg. Overall, the pharmacological
      effects of apremilast are consistent with those of a targeted PDE4 inhibitor,
      with selective effects on innate immune responses and a wide therapeutic index
      compared to its gastrointestinal side effects.

PMID- 24882691
TI  - Enhanced education and physiotherapy before knee replacement; is it worth it? A
      systematic review.
AB  - BACKGROUND: Around 20% of knee replacement have an unsatisfactory outcome. Pre
      operative physiotherapy and education have been proposed to improve post
      operative outcomes. OBJECTIVES: This systematic review evaluated whether these
      factors improved length of stay and patient reported outcomes after knee
      replacement surgery. DATA SOURCES: Medline, Embase, CINAHL, Cochrane Central
      Register of Controlled Trials, PsycINFO and PEDro were searched on the 1st
      January 2013. STUDY SELECTION OR ELIGIBILITY CRITERIA: Randomised or quasi
      randomised studies assessing either pre-operative education or physiotherapy on
      patients undergoing a planned total or partial knee replacement were included in
      the review. Only studies with a control group receiving a defined standard of pre
      operative care were included. RESULTS: Eleven studies met the inclusion criteria
      set. Two studies analysed the effect of pre-operative education, seven pre
      operative treatment by a physiotherapist and two studies used both factors. No
      study found significant differences in validated joint specific patient reported
      outcome measures. The education studies found a decrease in pre-operative
      expectation and an improvement in knowledge, flexion and regularity of exercise.
      Two studies found an improvement in muscle strength in the group treated by a
      physiotherapist at three months. The combination of education and physiotherapy
      was shown to reduce patient length of stay and cost in one study. CONCLUSION: The
      evidence reviewed is insufficient to support the implementation of either pre
      operative education or physiotherapy programmes. The combination of pre-operative
      education and treatment by a physiotherapist may reduce the medical costs
      associated with surgery.

PMID- 24882692
TI  - Menkes disease in Korea: ATP7A mutation and epilepsy phenotype.
AB  - OBJECTIVE: Menkes disease (MD) is an X-linked recessive disorder characterized by
      progressive neuro-degeneration. There are few reports of epilepsy and
      electroencephalography (EEG) findings and few reports of MD patients in Korea. We
      explored MD genotypes and phenotypes, including epilepsy, in Korean patients.
      PATIENTS AND METHODS: All patients diagnosed as MD in our hospital, seven males,
      were included in this study. Their medical records and EEG findings were reviewed
      retrospectively. RESULTS: All male patients had developmental delay/regression
      with hypotonia, and the appearance of their hair and skin was characteristic of
      MD. A recurrent missense mutation was found in two patients. Two nonsense
      mutations and one gross deletion were also found. The five male patients with
      identified molecular defects experienced anticonvulsant-resistant seizures. EEGs
      in focal seizures usually revealed interictal focal epileptiform discharges over
      the posterior region without focal slowing. This was followed by modified
      hypsarrhythmia with less polymorphic background activity in spasms and anteriorly
      dominant diffuse slowing with generalized and multifocal epileptiform discharges
      in myoclonic or generalized tonic seizures. Two patients with the same G727R
      missense mutation both developed seizures that evolved with age but differed in
      severity. CONCLUSIONS: G727R missense mutation may be relatively common in Korea,
      as in other countries. There was no clear correlation of genotype with phenotype,
      even in epilepsy and EEG abnormalities.

PMID- 24882694
TI  - CFTR functional measurements in human models for diagnosis, prognosis and
      personalized therapy: Report on the pre-conference meeting to the 11th ECFS Basic
      Science Conference, Malta, 26-29 March 2014.

PMID- 24882693
TI  - Molecular conformation of the full-length tumor suppressor NF2/Merlin--a small
      angle neutron scattering study.
AB  - The tumor suppressor protein Merlin inhibits cell proliferation upon establishing
      cell-cell contacts. Because Merlin has high level of sequence similarity to the
      Ezrin-Radixin-Moesin family of proteins, the structural model of Ezrin-Radixin
      Moesin protein autoinhibition and cycling between closed/resting and open/active
      conformational states is often employed to explain Merlin function. However,
      recent biochemical studies suggest alternative molecular models of Merlin
      function. Here, we have determined the low-resolution molecular structure and
      binding activity of Merlin and a Merlin(S518D) mutant that mimics the
      inactivating phosphorylation at S518 using small-angle neutron scattering and
      binding experiments. Small-angle neutron scattering shows that, in solution, both
      Merlin and Merlin(S518D) adopt a closed conformation, but binding experiments
      indicate that a significant fraction of either Merlin or Merlin(S518D) is capable
      of binding to the target protein NHERF1. Upon binding to the phosphatidylinositol
      4,5-bisphosphate lipid, the wild-type Merlin adopts a more open conformation than
      in solution, but Merlin(S518D) remains in a closed conformation. This study
      supports a rheostat model of Merlin in NHERF1 binding and contributes to
      resolving a controversy about the molecular conformation and binding activity of
      Merlin. 

PMID- 24882695
TI  - Response to the letter regarding article "A patient series of dual
      atrioventricular nodal nonreentrant tachycardia (DAVNNT)--an often overlooked
      diagnosis?".

PMID- 24882697
TI  - Maintenance of sinus rhythm after electrical cardioversion for recurrent atrial
      fibrillation following mitral valve surgery with or without associated
      radiofrequency ablation.
AB  - BACKGROUND: This study reports the outcomes of patients who underwent electrical
      cardioversion for atrial fibrillation recurrence following mitral valve surgery
      and associated radiofrequency ablation compared to those who did not undergo
      concomitant atrial fibrillation ablation. METHODS: The population consisted of
      116 patients with persistent/long-standing persistent AF who underwent mitral
      valve surgery with (Group A, n=54) or without (Group B, n=62) associated
      radiofrequency ablation between January 2007 and January 2011 at three
      institutions and who subsequently underwent cardioversion for persistent atrial
      fibrillation within 12 months of their initial procedure. RESULTS: The mean
      follow-up duration was 30.7+/-9.4 months. Of the 104 patients with acute
      restoration of SR 42 (40.3%) had AF recurrence. The average time to recurrence
      after cardioversion was 7.3+/-4.2 days. Recurrence was significantly lower in
      patients undergoing ablation surgery (21.4%) than in those undergoing no ablation
      surgery (78.6%, p<0.001). Non-performed ablation procedure (p<0.001), time from
      surgery>=88 days and left atrial dimensions>=45.5 mm before cardioversion (both,
      p=0.005) were multivariable predictors of atrial fibrillation recurrence. In
      Group B the use of amiodarone was inversely correlated with recurrence of AF
      (p<0.001). This correlation was not significant (r=-0.02, p=0.85) in Group A.
      CONCLUSIONS: Electrical cardioversion for recurrent AF showed better results and
      stable recovery of sinus rhythm in patients undergoing concomitant surgical
      ablation during mitral valve surgery. This might be attributable to substrate
      modification caused by surgical lesions. Amiodarone improved the ECV-success rate
      only in patients with no associate ablation. Further larger randomized studies
      are necessary to confirm our findings.

PMID- 24882696
TI  - International comparisons of the management of patients with non-ST segment
      elevation acute myocardial infarction in the United Kingdom, Sweden, and the
      United States: The MINAP/NICOR, SWEDEHEART/RIKS-HIA, and ACTION Registry
      GWTG/NCDR registries.
AB  - OBJECTIVES: To compare management of patients with acute non-ST segment elevation
      myocardial infarction (NSTEMI) in three developed countries with national ongoing
      registries. BACKGROUND: Results from clinical trials suggest significant
      variation in care across the world. However, international comparisons in "real
      world" registries are limited. METHODS: We compared the use of in-hospital
      procedures and discharge medications for patients admitted with NSTEMI from 2007
      to 2010 using the unselective MINAP/NICOR [England and Wales (UK); n=137,009],
      the unselective SWEDEHEART/RIKS-HIA (Sweden; n=45,069), and the selective ACTION
      Registry-GWTG/NCDR [United States (US); n=147,438] clinical registries. RESULTS:
      Patients enrolled among the three registries were generally similar except those
      in the US who were younger but had higher rates of smoking, diabetes,
      hypertension, prior heart failure, and prior MI than in Sweden or in UK.
      Angiography and percutaneous coronary intervention (PCI) were performed more
      often in the US (76% and 44%) and Sweden (65% and 42%) relative to the UK (32%
      and 22%). Discharge betablockers were also prescribed more often in the US (89%)
      and Sweden (89%) than in the UK (76%). In contrast, discharge statins,
      angiotensin converting enzyme inhibitors/angiotensin receptor blockers
      (ACEI/ARB), and dual antiplatelet agents (among those not receiving PCI) were
      higher in the UK (92%, 79%, and 71%) than in the US (85%, 65%, 41%) and Sweden
      (81%, 69%, and 49%). CONCLUSIONS: The care for patients with NSTEMI differed
      substantially among the three countries. These differences in care among
      countries provide an opportunity for future comparative effectiveness research as
      well as identify opportunities for global quality improvement.

PMID- 24882699
TI  - Co-activation of upper limb muscles during reaching in post-stroke subjects: an
      analysis of the contralesional and ipsilesional limbs.
AB  - The purpose of this study was to analyze the change in antagonist co-activation
      ratio of upper-limb muscle pairs, during the reaching movement, of both
      ipsilesional and contralesional limbs of post-stroke subjects. Nine healthy and
      nine post-stroke subjects were instructed to reach and grasp a target, placed in
      the sagittal and scapular planes of movement. Surface EMG was recorded from
      postural control and movement related muscles. Reaching movement was divided in
      two sub-phases, according to proximal postural control versus movement control
      demands, during which antagonist co-activation ratios were calculated for the
      muscle pairs LD/PM, PD/AD, TRIlat/BB and TRIlat/BR. Post-stroke's ipsilesional
      limb presented lower co-activation in muscles with an important role in postural
      control (LD/PM), comparing to the healthy subjects during the first sub-phase,
      when the movement was performed in the sagittal plane (p<0.05). Conversely, the
      post-stroke's contralesional limb showed in general an increased co-activation
      ratio in muscles related to movement control, comparing to the healthy subjects.
      Our findings demonstrate that, in post-stroke subjects, the reaching movement
      performed with the ipsilesional upper limb seems to show co-activation
      impairments in muscle pairs associated to postural control, whereas the
      contralesional upper limb seems to have signs of impairment of muscle pairs
      related to movement. 

PMID- 24882698
TI  - The MI SYNTAX score for risk stratification in patients undergoing primary
      percutaneous coronary intervention for treatment of acute myocardial infarction:
      a substudy of the COMFORTABLE AMI trial.
AB  - BACKGROUND: To investigate the performance of the MI Sxscore in a multicentre
      randomised trial of patients undergoing primary percutaneous coronary
      intervention (PPCI). METHODS AND RESULTS: The MI Sxscore was prospectively
      determined among 1132 STEMI patients enrolled into the COMFORTABLE AMI trial,
      which randomised patients to treatment with bare-metal (BMS) or biolimus-eluting
      (BES) stents. Patient- (death, myocardial infarction, any revascularisation) and
      device-oriented (cardiac death, target-vessel MI, target lesion
      revascularisation) major adverse cardiac events (MACEs) were compared across MI
      Sxscore tertiles and according to stent type. The median MI SXscore was 14 (IQR:
      9-21). Patients were divided into tertiles of Sxscorelow (<=10),
      Sxscoreintermediate (11-18) and Sxscorehigh (>=19). At 1 year, patient-oriented
      MACE occurred in 15% of the Sxscorehigh, 9% of the Sxscoreintermediate and 5% of
      the Sxscorelow tertiles (p<0.001), whereas device-oriented MACE occurred in 8% of
      the Sxscorehigh, 6% of the Sxscoreintermediate and 4% of the Sxscorelow tertiles
      (p=0.03). Addition of the MI Sxscore to the TIMI risk score improved prediction
      of patient- (c-statistic value increase from 0.63 to 0.69) and device-oriented
      MACEs (c-statistic value increase from 0.65 to 0.70). Differences in the risk for
      device-oriented MACE between BMS and BES were evident among Sxscorehigh (13% vs.
      4% HR 0.33 (0.15-0.74), p=0.007 rather than those in Sxscorelow: 4% vs. 3% HR
      0.68 (0.24-1.97), p=0.48) tertiles. CONCLUSIONS: The MI Sxscore allows risk
      stratification of patient- and device-oriented MACEs among patients undergoing
      PPCI. The addition of the MI Sxscore to the TIMI risk score is of incremental
      prognostic value among patients undergoing PPCI for treatment of STEMI.

PMID- 24882700
TI  - The potential role of atypical antipsychotics for the treatment of posttraumatic
      stress disorder.
AB  - Despite the fact that the majority of currently available treatment guidelines
      propose antidepressants as the first-line pharmacological therapy for
      posttraumatic stress disorder (PTSD), a substantial portion of patients fail to
      show an adequate response following this type of treatment. In this context, a
      number of small, open-label studies and randomized controlled clinical trials
      (RCTs) have found atypical antipsychotics (AAs) to be a beneficial treatment for
      patients with PTSD. Thus, the present meta-analysis was conducted to enhance the
      sample size power and further the current understanding of the role of AAs for
      the treatment of PTSD. An extensive search of several databases identified 12
      appropriate RCTs and available data from 9 of these (n = 497) were included in
      the final meta-analysis. AAs may have potential benefits for the treatment of
      PTSD as indicated by changes from baseline of the total score on the Clinician
      Administered PTSD Scale (CAPS; standardized mean difference [SMD] = -0.289, 95%
      confidence intervals [CIs] = -0.471, -0.106), P = 0.002). Additionally, AAs were
      found to be significantly more effective (P < 0.0001) than a placebo in terms of
      change from baseline for the intrusion sub-score on the CAPS (SMD = -0.373, 95%
      CIs = -0.568, -0.178) but there were no significant reductions for the avoidance
      and hyperarousal sub-symptoms. The responder rate and rate of improvement of
      depressive symptoms were also significantly higher in the AA group than the
      placebo group (P = 0.004 and P < 0.0001, respectively). However, the present
      results should be interpreted carefully and be translated into clinical practice
      only with due consideration of the limited quality and quantity of existing RCTs
      included in this analysis. 

PMID- 24882702
TI  - Population genetic structure of the Lyme disease vector Ixodes scapularis at an
      apparent spatial expansion front.
AB  - Modeling and empirical evidence suggests that Lyme disease is undergoing
      geographic expansion from principal foci in the midwestern and northeastern
      United States. Virginia is at the southern edge of the current expansion zone and
      has seen dramatic rise in human Lyme disease cases since 2007, potentially owing
      to a recent increase in vector abundance. Ixodes scapularis is known throughout
      the eastern US but behavioral or physiological variation between northern and
      southern lineages might lead northern-variant ticks to more frequently parasitize
      humans. We hypothesized that recent spatial and numerical increase in Lyme
      disease cases is associated with demographic and/or spatial expansion of I.
      scapularis and that signals of these phenomena would be detectable and
      discernable in population genetic signals. In summer and fall 2011, we collected
      nymphal I. scapularis by drag sampling and adult I. scapularis from deer
      carcasses at hunting check stations at nine sites arranged along an east-west
      transect through central Virginia. We analyzed 16S mtDNA sequences data from up
      to 24 I. scapularis individuals collected from each site and detected a total of
      24 haplotypes containing 29 segregating sites. We found no evidence for
      population genetic structure among these sites but we did find strong signals of
      both demographic and spatial expansion throughout our study system. We found two
      haplotypes (one individual each) representing a lineage of ticks that is only
      found in the southeastern United States, with the remaining individuals
      representing a less genetically diverse clade that is typical of the northern
      United States, but that has also been detected in the American South. Taken
      together, these results lead us to conclude that I. scapularis populations in
      Virginia are expanding and that this expansion may account for recent observed
      increases in Lyme disease. 

PMID- 24882701
TI  - The aggression and behavioral abnormalities associated with monoamine oxidase A
      deficiency are rescued by acute inhibition of serotonin reuptake.
AB  - The termination of serotonin (5-hydroxytryptamine, 5-HT) neurotransmission is
      regulated by its uptake by the 5-HT transporter (5-HTT), as well as its
      degradation by monoamine oxidase (MAO)-A. MAO-A deficiency results in a wide set
      of behavioral alterations, including perseverative behaviors and social deficits.
      These anomalies are likely related to 5-HTergic homeostatic imbalances; however,
      the role of 5-HTT in these abnormalities remains unclear. To ascertain the role
      of 5-HTT in the behavioral anomalies associated to MAO-A deficiency, we tested
      the behavioral effects of its blocker fluoxetine on perseverative, social and
      aggressive behaviors in transgenic animals with hypomorphic or null-allele MAO-A
      mutations. Acute treatment with the 5-HTT blocker fluoxetine (10 mg/kg, i.p.)
      reduced aggressive behavior in MAO-A knockout (KO) mice and social deficits in
      hypomorphic MAO-A(Neo) mice. Furthermore, this treatment also reduced
      perseverative responses (including marble burying and water mist-induced
      grooming) in both MAO-A mutant genotypes. Both MAO-A mutant lines displayed
      significant reductions in 5-HTT expression across the prefrontal cortex, amygdala
      and striatum, as quantified by immunohistochemical detection; however, the down
      regulation of 5-HTT in MAO-A(Neo) mice was more pervasive and widespread than in
      their KO counterparts, possibly indicating a greater ability of the hypomorphic
      line to enact compensatory mechanisms with respect to 5-HT homeostasis.
      Collectively, these findings suggest that the behavioral deficits associated with
      low MAO-A activity may reflect developmental alterations of 5-HTT within 5
      HTergic neurons. Furthermore, the translational implications of our results
      highlight 5-HT reuptake inhibition as an interesting approach for the control of
      aggressive outbursts in MAO-A deficient individuals. 

PMID- 24882703
TI  - Adsorption behaviour of direct yellow 50 onto cotton fiber: equilibrium, kinetic
      and thermodynamic profile.
AB  - This study investigated the adsorption of direct yellow 50 onto cotton fiber from
      aqueous solution by using parameters, such as pH, temperature, contact time,
      initial dye concentration and the effect of sodium sulphate, tetrasodium edate
      and trisodium citrate. The extent of dye adsorption increased with increasing
      contact time, temperature and solution concentration. The experimental data were
      analyzed by the Langmuir and Freundlich models of adsorption. It was found that
      the Langmuir equation fit better than the Freundlich equation. The results show
      that the presence of SE and SC significantly enhance the dye adsorption onto
      cotton fiber. In addition, the adsorption data obtained at different temperatures
      of DY50 onto cotton fiber were applied to pseudo first-order, pseudo second-order
      and intraparticle diffusion models. The rates of adsorption were found to conform
      to pseudo second-order kinetics with good correlation. Also, free energy of
      adsorption (DeltaG(#)), enthalpy (DeltaH(#)), and entropy (DeltaS(#)) changes
      were determined to predict the nature of adsorption. The positive value of the
      enthalpy change indicated that the adsorption is endothermic process. The
      activation energy, Ea, is ranged between 1.9 and 3.9kJmol(-1) indicated that the
      adsorption process is a physisorption. This low value of Ea generally indicates
      diffusion controlled process. 

PMID- 24882705
TI  - The cytosolic bacterial peptidoglycan sensor Nod2 affords stem cell protection
      and links microbes to gut epithelial regeneration.
AB  - The intestinal crypt is a site of potential interactions between microbiota
      products, stem cells, and other cell types found in this niche, including Paneth
      cells, and thus offers a potential for commensal microbes to influence the host
      epithelium. However, the complexity of this microenvironment has been a challenge
      to deciphering the underlying mechanisms. We used in vitro cultured organoids of
      intestinal crypts from mice, reinforced with in vivo experiments, to examine the
      crypt-microbiota interface. We find that within the intestinal crypt, Lgr5(+)
      stem cells constitutively express the cytosolic innate immune sensor Nod2 at
      levels much higher than in Paneth cells. Nod2 stimulation by its bona fide
      agonist, muramyl-dipeptide (MDP), a peptidoglycan motif common to all bacteria,
      triggers stem cell survival, which leads to a strong cytoprotection against
      oxidative stress-mediated cell death. Thus, gut epithelial restitution is Nod2
      dependent and triggered by the presence of microbiota-derived molecules.

PMID- 24882707
TI  - Assembling the dominant accounts of youth drug use in Australian harm reduction
      drug education.
AB  - Education programs are a central element of Australian harm reduction drug
      policy. Considered less judgmental and more effective than the punitive policies
      of Australia's past, harm reduction drug education is premised on the goal of
      reducing 'risks' and harms associated with illicit drug use rather than an
      elimination of use per se. In this article I analyse two sets of key texts
      designed to reduce drug related harm in Australia: harm reduction teaching
      resources designed for classroom use and social marketing campaigns that are
      targeted to a more general audience. I identify two significant accounts of young
      people's drug use present in Australian harm reduction drug education: 'damaged
      mental health' and 'distress'. I then draw on some of Deleuze and Guattari's key
      concepts to consider the harm reducing potential these accounts may have for
      young people's drug using experiences. To demonstrate the potential limitations
      of current drug education, I refer to an established body of work examining young
      people's experiences of chroming. From here, I argue that the accounts of
      'damaged mental health' and 'distress' may work to limit the capacity of young
      drug users to practice safer drug use. In sum, current Australian harm reduction
      drug education and social marketing may be producing rather than reducing drug
      related harm. 

PMID- 24882704
TI  - Infection mobilizes hematopoietic stem cells through cooperative NOD-like
      receptor and Toll-like receptor signaling.
AB  - Adult hematopoietic stem cells (HSCs) are maintained in specialized niches within
      the bone marrow under steady-state conditions and mobilize for extramedullary
      hematopoiesis during periods of stress such as bacterial infections. However, the
      underlying mechanisms are unclear. We show that systemic infection of mice with
      Escherichia coli, commonly associated with bacteremia in humans, mobilizes
      functional HSCs to the spleen. Accumulation of splenic HSCs (CD150+CD48-Lin(
      /low)Sca1+cKit+) was diminished in TLR4-deficient and RIPK2-deficient mice,
      implicating TLRs and cytosolic NOD1/NOD2 signaling in the process. Accordingly,
      dual stimulation of NOD1 and TLR4 in radio-resistant cells alone was sufficient
      to mobilize HSCs, while TLR4 expression on HSCs was dispensable. Mechanistically,
      TLR4 and NOD1 synergistically induced granulocyte colony-stimulating factor (G
      CSF), which was required for extramedullary HSC accumulation. Mobilized HSCs and
      progenitor cells gave rise to neutrophils and monocytes and contributed to
      limiting secondary infection. 

PMID- 24882708
TI  - Making drug policy together: reflections on evidence, engagement and
      participation.
AB  - This commentary considers the relationship between evidence, engagement and
      participation in drug policy governance. It argues that the use of various forms
      of evidence (for example, statistical data and service user narratives) is
      critical for meaningful stakeholder engagement and public participation in drug
      policy, as well as effective policy design and implementation. The respective
      roles of these different kinds of evidence in consultation processes need to be
      better understood. It discusses the limits of evidence, which it suggests is
      rarely conclusive or decisive for drug policy. This is partly because of the
      incompleteness of most research agendas and the lack of consensus among
      researchers, but also because issues in drug policy are inherently contestable,
      involving considerations that lie outside the competency of drug policy
      specialist as such. In particular, this is because they involve normative and
      evaluative issues that are properly political (for example, about the relative
      weight to be accorded to different kinds of harm and benefit). It concludes by
      supporting calls for a more nuanced understanding of the relationship between
      evidence, engagement and politics than is implicit in the term 'evidence based
      policy'. It also argues that we should view the inherent contestability of drug
      policy not as something that can or should be resolved by 'objective' evidence,
      but as a source of vitality and creativity in policy development and evaluation. 

PMID- 24882706
TI  - Mutations of CEP83 cause infantile nephronophthisis and intellectual disability.
AB  - Ciliopathies are a group of hereditary disorders associated with defects in cilia
      structure and function. The distal appendages (DAPs) of centrioles are involved
      in the docking and anchoring of the mother centriole to the cellular membrane
      during ciliogenesis. The molecular composition of DAPs was recently elucidated
      and mutations in two genes encoding DAPs components (CEP164/NPHP15, SCLT1) have
      been associated with human ciliopathies, namely nephronophthisis and
      orofaciodigital syndrome. To identify additional DAP components defective in
      ciliopathies, we independently performed targeted exon sequencing of 1,221 genes
      associated with cilia and 5 known DAP protein-encoding genes in 1,255 individuals
      with a nephronophthisis-related ciliopathy. We thereby detected biallelic
      mutations in a key component of DAP-encoding gene, CEP83, in seven families. All
      affected individuals had early-onset nephronophthisis and four out of eight
      displayed learning disability and/or hydrocephalus. Fibroblasts and tubular renal
      cells from affected individuals showed an altered DAP composition and ciliary
      defects. In summary, we have identified mutations in CEP83, another DAP-component
      encoding gene, as a cause of infantile nephronophthisis associated with central
      nervous system abnormalities in half of the individuals. 

PMID- 24882709
TI  - Peptide drugs that have been developed to treat type 2 diabetes show
      neuroprotective effects.

PMID- 24882711
TI  - Specific pattern of cell cycle during limb fetal myogenesis.
AB  - Tight regulation of cell proliferation and differentiation is required to ensure
      proper growth during development and post-natal life. The source and nature of
      signals regulating cell proliferation are not well identified in vivo. We
      investigated the specific pattern of proliferating cells in mouse limbs, using
      the Fluorescent ubiquitynation-based cell-cycle indicator (Fucci) system, which
      allowed the visualization of the G1, G1/S transition and S/G2/M phases of the
      cell cycle in red, yellow or green fluorescent colors, respectively. We also used
      the retroviral RCAS system to express a Fucci cassette in chick embryos. We
      performed a comprehensive analysis of the cell cycle state of myogenic cells in
      fetal limb muscles, adult myoblast primary cultures and isolated muscle fiber
      cultures using the Fucci transgenic mice. We found that myonuclei of terminally
      differentiated muscle fibers displayed Fucci red fluorescence during mouse and
      chick fetal development, in adult isolated muscle fiber (ex vivo) and adult
      myoblast (in vitro) mouse cultures. This indicated that myonuclei exited from the
      cell cycle in the G1 phase and are maintained in a blocked G1-like state. We also
      found that cycling muscle progenitors and myoblasts in G1 phase were not
      completely covered by the Fucci system. During mouse fetal myogenesis, Pax7+
      cells labeled with the Fucci system were observed mostly in S/G2/M phases.
      Proliferating cells in S/G2/M phases displayed a specific pattern in mouse fetal
      limbs, delineating individualized muscles. In addition, we observed more Pax7+
      cells in S/G2/M phases at muscle tips, compared to the middle of muscles. These
      results highlight a specific spatial regionalization of cycling cells at the
      muscle borders and muscle-tendon interface during fetal development. 

PMID- 24882710
TI  - SUMV-1 antagonizes the activity of synthetic multivulva genes in Caenorhabditis
      elegans.
AB  - Chromatin regulators contribute to the developmental control of gene expression.
      In the nematode Caenorhabditis elegans, the roles of chromatin regulation in
      development have been explored in several contexts, including vulval
      differentiation. The synthetic multivulva (synMuv) genes are regulators of vulval
      development in C. elegans and the proteins encoded by these genes include
      components of several histone modification and chromatin remodelling complexes.
      By inhibiting ectopic expression of the epidermal growth factor (LIN-3) in the
      nematode hypodermis, the synMuv genes prevent inappropriate vulval induction. In
      a forward genetic screen for modifiers of the expression of a hypodermal reporter
      gene, we identified a mutation that results in increased expression of the
      reporter. This mutation also suppresses ectopic vulval induction in synMuv
      mutants and we have consequently named the affected gene suppressor of synthetic
      multivulva-1 (sumv-1). We show that SUMV-1 is required in the hypodermis for the
      synMuv phenotype and that loss of sumv-1 function suppresses ectopic expression
      of lin-3 in synMuv mutant animals. In yeast two-hybrid assays SUMV-1 physically
      interacts with SUMV-2, and reduction of sumv-2 function also suppresses the
      synMuv phenotype. We identified similarities between SUMV-1 and SUMV-2 and
      mammalian proteins KAT8 NSL2 and KAT8 NSL3, respectively, which are components of
      the KAT8/MOF histone acetyltransferase complex. Reduction of function of mys-2,
      which encodes the enzymatic component of the KAT8/MOF complex, also suppresses
      the synMuv phenotype, and MYS-2 physically interacts with SUMV-2 in yeast two
      hybrid assays. Together these observations suggest that SUMV-1 and SUMV-2 may
      function together with MYS-2 in a nematode KAT8/MOF-like complex to antagonise
      the activity of the synMuv genes. 

PMID- 24882712
TI  - Migratory neural crest cell alphaN-catenin impacts chick trigeminal ganglia
      formation.
AB  - Neural crest cells are an embryonic cell population that is crucial for proper
      vertebrate development. Initially localized to the dorsal neural folds,
      premigratory neural crest cells undergo an epithelial-to-mesenchymal transition
      (EMT) and migrate to their final destinations in the developing embryo. Together
      with epidermally-derived placode cells, neural crest cells then form the cranial
      sensory ganglia of the peripheral nervous system. Our prior work has shown that
      alphaN-catenin, the neural subtype of the adherens junction alpha-catenin
      protein, regulates cranial neural crest cell EMT by controlling premigratory
      neural crest cell cadherin levels. Although alphaN-catenin down-regulation is
      critical for initial neural crest cell EMT, a potential role for alphaN-catenin
      in later neural crest cell migration, and formation of the cranial ganglia, has
      not been examined. In this study, we show for the first time that migratory
      neural crest cells that will give rise to the cranial trigeminal ganglia express
      alphaN-catenin and Cadherin-7. alphaN-catenin loss- and gain-of-function
      experiments reveal effects on the migratory neural crest cell population that
      include subsequent defects in trigeminal ganglia assembly. Moreover, alphaN
      catenin perturbation in neural crest cells impacts the placode cell contribution
      to the trigeminal ganglia and also changes neural crest cell Cadherin-7 levels
      and localization. Together, these results highlight a novel function for alphaN
      catenin in migratory neural crest cells that form the trigeminal ganglia. 

PMID- 24882713
TI  - A fluorescent probe for imaging symmetric and asymmetric cell division in
      neurosphere formation.
AB  - We report here a novel fluorescent chemical probe which stains distinct neural
      stem/progenitor cells (NSPCs) by binding to acid ceramidase in mouse
      neurospheres. is distributed evenly or unevenly to the daughter cells during
      multiple mitoses enabling the live imaging of symmetric and asymmetric divisions
      of isolated NSPCs. 

PMID- 24882714
TI  - Protein fingerprint of colorectal cancer, adenomatous polyps, and normal mucosa
      using ProteinChip analysis on laser capture microdissected cells.
AB  - To find new biomarkers and establish histopathology protein fingerprint models
      for early detection of colorectal cancer (CRC), laser capture microdissection
      (LCM) was utilized to obtain 3 groups of cells of interest--CRC tissues, their
      adjacent normal colorectal tissues, and their adjacent adenomatous polyps tissues
      -from the same 12 CRC patients. Each sample was then detected by surface-enhanced
      laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF-MS)
      technology and CM10 protein chip as well as bioinformatics tools. Model 1 formed
      by 15 protein peaks could be used to distinguish CRC tissues from normal tissues.
      The diagnostic pattern constructed using support vector machine (SVM) including
      the 15 proteins showed maximum Youden index (YI). Model 2 formed by 14 protein
      peaks could be used to distinguish CRC tissues from adenomatous polyps tissues.
      The two patterns were validated and the results showed that the sensitivity and
      specificity were both 100.0%. Model 3 formed by 15 protein peaks could
      distinguish adenomatous polyps tissues from normal tissues with a sensitivity of
      92.3% and specificity of 100.0%. The protein peaks m/z 3570 and 5224 were
      identified in screening for changes during cancer progression. Peak 5224 was
      significantly upregulated in CRC. However, peak 3570 was significantly
      downregulated in CRC. LCM technology coupled with SELDI protein chip and
      bioinformatics approaches could effectively screen the differentially expressed
      protein profiles and establish molecular diagnosis models with high sensitivity
      and specificity for CRC.

PMID- 24882716
TI  - Advances in mechanisms of systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a complex autoimmune disease associated
      with hormonal, environmental, and genetic factors and linked to the tolerance
      breakdown of B and T cells to self-antigens. SLE is characterized by the presence
      in patient serum of autoantibodies raised against nuclear components. Association
      of these antibodies to self-antigens, complement factors, DNA, and particular
      proteins will form circulating immune complexes (CIC) which can deposit in
      several organs, causing tissue damage and clinical manifestations. Historically,
      SLE is considered as an adaptive immune system disorder. Over the past decade,
      advances in the understanding of SLE pathogenesis placed the innate immune system
      as a key player in perpetuating and amplifying this systemic disease. In this
      review, we summarize some recent key advances in understanding the SLE immune
      pathogenesis with a particular focus on newly discovered key factors from the
      innate immune system and how they influence the pathogenic adaptive immune
      system: neutrophils and neutrophil extracellular traps (NETs), plasmacytoid
      dendritic cells (pDCs) and type I interferons, basophils and autoreactive IgE,
      monocytes/macrophages and the inflammasome. Recent advances on B and T cell
      involvement in the SLE pathogenesis mechanisms are also discussed. Although the
      disease is clinically, genetically, and immunologically heterogeneous between
      affected individuals, the latest discoveries are offering new promising
      therapeutic strategies. 

PMID- 24882717
TI  - Inflammatory disease and the human microbiome.
AB  - The human body is a superorganism in which thousands of microbial genomes
      continually interact with the human genome. A range of physical and neurological
      inflammatory diseases are now associated with shifts in microbiome composition.
      Seemingly disparate inflammatory conditions may arise from similar disruption of
      microbiome homeostasis. Intracellular pathogens long associated with inflammatory
      disease are able to slow the innate immune response by dysregulating activity of
      the VDR nuclear receptor. This facilitates the ability of other species to
      gradually accumulate in tissue and blood, where they generate proteins and
      metabolites that significantly interfere with the body's metabolic processes. The
      microbes that contribute to this dysfunction are often inherited from family
      members. Immunosuppressive therapies for inflammatory disease allow pathogens
      driving these processes to spread with greater ease. In contrast to
      immunosuppression, treatments that stimulate the immune system seem to allow for
      reversal of this pathogen-induced genomic dysregulation. 

PMID- 24882715
TI  - Current siRNA targets in atherosclerosis and aortic aneurysm.
AB  - Atherosclerosis (ATH) and aortic aneurysms (AA) remain challenging chronic
      diseases that confer high morbidity and mortality despite advances in medical,
      interventional, and surgical care. RNA interference represents a promising
      technology that may be utilized to silence genes contributing to ATH and AA.
      Despite positive results in preclinical and some clinical feasibility studies,
      challenges such as target/sequence validation, tissue specificity, transfection
      efficiency, and mitigation of unwanted off-target effects remain to be addressed.
      In this review the most current targets and some novel approaches in siRNA
      delivery are being discussed. Due to the plethora of investigated targets, only
      studies published between 2010 and 2014 were included. 

PMID- 24882718
TI  - Alternative approaches to prevent androgen action in prostate cancer: are we
      there yet?
AB  - Prostate cancer is the most frequently diagnosed cancer and the second leading
      cause of cancer deaths in men in the U.S. Prostate cancer deaths are due to
      failure of androgen deprivation therapy (ADT). ADT is the standard of care for
      non-organ confined prostate cancer and inhibits action of androgen receptor (AR),
      which is necessary for the growth of prostate cancer. ADT blocks AR activity by
      preventing either production of its ligands or interaction between AR and its
      ligands. Following an initial remission, almost all patients experience prostate
      cancer recurrence during ADT. Remarkably, prostate cancer that reemerges remains
      dependent on AR. This recognition has led to the recent development of novel
      treatment strategies that focus on alternative means to target ligand production
      and availability for AR. These therapies induce remission and offer moderate
      survival benefits but none are curative while all are associated with significant
      side effects. We propose that an alternative tactic to achieve the beneficial
      effects of ADT could be explored by targeting a different step in the AR
      signaling cascade, namely the biological consequences of AR activation. Insights
      in molecular regulation of AR function and genome-wide AR action could be used to
      develop therapeutic interventions that focus on eliminating only distinct AR
      dependent biological processes responsible for aggressive prostate cancer cell
      behavior. Such selective forms of ADT could be used alone or in combination with
      existing therapies to improve prostate cancer therapeutic outcome in a stage
      specific and personalized manner. 

PMID- 24882719
TI  - Rationale for targeting the Ras/MAPK pathway in triple-negative breast cancer.
AB  - "Triple negative" breast cancer (TNBC) is the most aggressive and least common
      clinical subtype of breast cancer. As its nomenclature implies, TNBC lacks
      specific biomarker expression marking response to an effective targeted therapy.
      The incidence of TNBC is higher in young minority women who suffer from high
      rates of early recurrence and death from their disease. Mounting preclinical
      evidence supports targeting the Ras/MAPK cell signaling pathway in the TNBC
      subtype, despite large genomic surveys such as The Cancer Genome Atlas
      demonstrating infrequent canonical mutations in this pathway. Due to the early
      spread of TNBC, targeted treatment in the neoadjuvant setting may offer the
      effective therapeutic punch needed to eliminate micro-metastatic disease and
      reduce mortality. Herein, we will review the evidence supporting clinical trials
      of targeted inhibitors of the Ras/MAPK pathway in TNBC, and discuss the obstacles
      and opportunities of this approach. 

PMID- 24882720
TI  - Novel therapeutic approaches for celiac disease.
AB  - Celiac disease, which mainly affects the small intestine, is the only systemic
      autoimmune disorder with an identified environmental trigger which is dietary
      gluten. Lifelong adherence to a strict gluten free diet (GFD) is currently the
      only accepted treatment. Celiac disease is increasingly diagnosed and the GFD is
      known to be associated with a large treatment burden. Furthermore, a substantial
      number of celiac disease patients show an incomplete clinical response to the
      GFD. These factors have led to demands for the development and testing of novel,
      non-dietary, therapeutic agents that are both safe and effective. Celiac disease
      pathogenesis is well elucidated which has greatly aided targeted drug
      development. Compounds currently being tested in phase II clinical trials include
      glutenase enzymes (to detoxify gluten) and a tight junction modulator (to reduce
      access of gluten peptides to lamina propria antigen presenting cells). Other
      promising approaches include inhibition of the transglutaminase 2 enzyme,
      blocking antigen presentation by HLA-DQ2 or HLA-DQ8, induction of tolerance, and
      modulation of the inflammatory response. It is hoped that non-dietary therapy for
      celiac disease will become available in the coming years and can both reduce the
      burden of treatment of celiac disease and help patients whose symptoms do not
      respond completely to the GFD. 

PMID- 24882721
TI  - Widespread neuron-specific transgene expression in brain and spinal cord
      following synapsin promoter-driven AAV9 neonatal intracerebroventricular
      injection.
AB  - Adeno-associated viral (AAV) gene transfer holds great promise for treating a
      wide-range of neurodegenerative disorders. The AAV9 serotype crosses the blood
      brain barrier and shows enhanced transduction efficiency compared to other
      serotypes, thus offering advantageous targeting when global transgene expression
      is required. Neonatal intravenous or intracerebroventricular (i.c.v.) delivery of
      recombinant AAV9 (rAAV9) have recently proven effective for modeling and treating
      several rodent models of neurodegenerative disease, however, the technique is
      associated with variable cellular tropism, making tailored gene transfer a
      challenge. In the current study, we employ the human synapsin 1 (hSYN1) gene
      promoter to drive neuron-specific expression of green fluorescent protein (GFP)
      after neonatal i.c.v. injection of rAAV9 in mice. We observed widespread GFP
      expression in neurons throughout the brain, spinal cord, and peripheral nerves
      and ganglia at 6 weeks-of-age. Region-specific quantification of GFP expression
      showed high neuronal transduction rates in substantia nigra pars reticulata
      (43.9+/-5.4%), motor cortex (43.5+/-3.3%), hippocampus (43.1+/-2.7%), cerebellum
      (29.6+/-2.3%), cervical spinal cord (24.9+/-3.9%), and ventromedial striatum
      (16.9+/-4.3%), among others. We found that 14.6+/-2.2% of neuromuscular junctions
      innervating the gastrocnemius muscle displayed GFP immunoreactivity. GFP
      expression was identified in several neuronal sub-types, including nigral
      tyrosine hydroxylase (TH)-positive dopaminergic cells, striatal dopamine- and
      cAMP-regulated neuronal phosphoprotein (DARPP-32)-positive neurons, and choline
      acetyltransferase (ChAT)-positive motor neurons. These results build on
      contemporary gene transfer techniques, demonstrating that the hSYN1 promoter can
      be used with rAAV9 to drive robust neuron-specific transgene expression
      throughout the nervous system. 

PMID- 24882722
TI  - Chronic toluene exposure induces cell proliferation in the mice SVZ but not
      migration through the RMS.
AB  - Abuse of toluene-containing inhalants is associated to various cognitive
      impairments that have been partly associated to deviation of the hippocampal
      neurogenesis processes during adulthood. In the present study we analyzed the
      effect of chronic toluene exposure (6000ppm) on cell proliferation and migration
      in the other selected area of the rodent brain where neurogenesis persist
      throughout adulthood, the subventricular zone of the lateral ventricle (SVZ). We
      used an anti-Ki67 antibody to evaluate SVZ cell proliferation, BrdU to evaluate
      cell survival and double-staining with BrdU and the migration marker doublecortin
      (DCX) to evaluate migration, by immunofluorescence 2h, 1, 5, 10 or 15 days after
      20 sessions of toluene exposure. We found that toluene induced an initial burst
      of cell proliferation in the SVZ but not a significant increase in migration
      toward the rostral migratory stream (RMS) or the number of cells that migrate to
      the olfactory bulb. In addition, we detected a small number of new migrating
      cells in the corpus callosum and striatum of control mice that was similar in
      toluene-exposed brains. These results may underline the homeostatic capabilities
      of the populations of dividing cells, previously demonstrated using other drugs
      of abuse and demonstrate that toluene misuse can alter cellular proliferation in
      the postnatal brain. 

PMID- 24882723
TI  - Interplay between intercellular signaling and cell movement in development.
AB  - Cell movement and local intercellular signaling are crucial components of
      morphogenesis during animal development. Intercellular signaling regulates the
      collective movement of a cell population via direct cell-cell contact. Cell
      movement, conversely, can influence local intercellular signaling by rearranging
      neighboring cells. Here, we first discuss theoretical models that address how
      intercellular signaling regulates collective cell movement during development.
      Examples include neural crest cell migration, convergent extension, and cell
      movement during vertebrate axis elongation. Second, we review theoretical studies
      on how cell movement may affect intercellular signaling, using the segmentation
      clock in zebrafish as an example. We propose that interplay between cell movement
      and intercellular signaling must be considered when studying morphogenesis in
      embryonic development. 

PMID- 24882725
TI  - Assessment of fetal exposure and maternal elimination of perfluoroalkyl
      substances.
AB  - In this study, we estimated the body burden (BB) of perfluoroalkyl substances
      (PFASs) in a fetus at the time of delivery, and elimination of PFASs in female
      adults during pregnancy; and explored the isomer branching pattern-related
      placental transfer of perfluorooctane sulfonate (PFOS). The mean BB of PFASs were
      3980 ng for PFOS and 2320 ng for perfluorooctanoic acid (PFOA), therefore, the
      average daily exposure doses via placental transfer were estimated to be 13.7 and
      8.32 ng per day for PFOS and PFOA, respectively, by dividing the BB of PFASs by
      gestational age. The total daily elimination of PFOS and PFOA in female adults
      through pregnancy was 30.1 and 11.4 ng per day, which indicates that pregnancy
      and child birth may reduce the PFASs levels in female adults. Further, branched
      PFOS was more readily transferred through the placenta than linear PFOS.

PMID- 24882726
TI  - Fruit pomace and waste frying oil as sustainable resources for the bioproduction
      of medium-chain-length polyhydroxyalkanoates.
AB  - Medium-chain-length polyhydroxyalkanoates (mcl-PHAs) are biobased and
      biodegradable alternatives to petrol-derived polymers, whose break-through has
      been prevented by high production cost. Therefore we investigated whether wastes
      from the food industry (nine types of fruit pomace including apricots, cherries
      and grapes, and waste frying oil) could replace the costly sugars and fatty acids
      typically used as carbon substrates for the bacterial fermentations. A selection
      of enzyme preparations was tested for converting the residual polysaccharides
      from the pomaces into fermentable monosaccharides. From the pomace of apricots,
      cherries and Solaris grapes, 47, 49 and 106gL(-1) glucose were recovered,
      respectively. Solaris grapes had the highest sugar content whereas apricots
      contained the fewest growth inhibitors. These two pomaces were assessed for their
      suitability to produce mcl-PHA in bioreactor. A 2-step fermentation was
      established with Pseudomonas resinovorans, hydrolyzed pomace as growth substrate
      and WFO as mcl-PHA precursor. Solaris grapes proved to be a very promising growth
      substrate, resulting in the production of 21.3gPHA(Lpomace)(-1) compared to 1.4g
      PHA (L pomace)(-1) for apricots. Finally, capillary zone electrophoresis analyses
      allowed monitoring of sugar and organic acid uptake during the fermentation on
      apricots, which led to the discovery of reverse diauxie in P. resinovorans. 

PMID- 24882724
TI  - Post-transcriptional RNA regulons affecting cell cycle and proliferation.
AB  - The cellular growth cycle is initiated and maintained by punctual, yet agile,
      regulatory events involving modifications of cell cycle proteins as well as
      coordinated gene expression to support cyclic checkpoint decisions. Recent
      evidence indicates that post-transcriptional partitioning of messenger RNA
      subsets by RNA-binding proteins help physically localize, temporally coordinate,
      and efficiently translate cell cycle proteins. This dynamic organization of mRNAs
      encoding cell cycle components contributes to the overall economy of the cell
      cycle consistent with the post-transcriptional RNA regulon model of gene
      expression. This review examines several recent studies demonstrating the
      coordination of mRNA subsets encoding cell cycle proteins during nuclear export
      and subsequent coupling to protein synthesis, and discusses evidence for mRNA
      coordination of p53 targets and the DNA damage response pathway. We consider how
      these observations may connect to upstream and downstream post-transcriptional
      coordination and coupling of splicing, export, localization, and translation.
      Published examples from yeast, nematode, insect, and mammalian systems are
      discussed, and we consider genetic evidence supporting the conclusion that
      dysregulation of RNA regulons may promote pathogenic states of growth such as
      carcinogenesis. 

PMID- 24882727
TI  - Anti-influenza virus activity of the ethanolic extract from Peperomia sui.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Peperomia sui Lin and Lu (Peperomia sui), a well
      known Taiwanese folk medicine, has a broad range of biological effects,
      especially in treatment of upper respiratory tract diseases. However, no previous
      study has explored the activity of Peperomia sui against influenza virus
      infections. This study was carried out to evaluate the anti-influenza virus
      activity and the potential virucidal effect of the ethanolic extract of Peperomia
      sui (PSE). METHODS: The anti-H6N1 avian influenza viral activity of PSE against
      the influenza virus A/Chicken/TW/0518/2011 (H6N1) in chicken fibroblast DF-1
      cells was evaluated by cell viability assay, hemagglutination assay,
      neuraminidase activity assay, indirect immunofluorescence assay and quantitative
      RT-PCR assay. RESULTS: PSE significantly increased the viability of cells that
      were infected by the H6N1 virus. PSE also suppressed the synthesis of viral
      nucleoprotein (NP), and inhibited the growth of the virus in DF-1 cells. Further,
      PSE inhibited the neuraminidase activity of H6N1 virus. CONCLUSIONS: The findings
      of this study provide important information for the exploitation and utilization
      of Peperomia sui in treatment of influenza infection.

PMID- 24882728
TI  - Insulin-sensitizing and insulin-mimetic activities of Sarcopoterium spinosum
      extract.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Sarcopoterium spinosum is an abundant plant in
      Israel, used by Bedouin medicinal practitioners for the treatment of diabetes. In
      our previous study we validated the anti-diabetic activity of Sarcopoterium
      spinosum. The aim of this study was to further clarify its mechanism of action.
      MATERIALS AND METHODS: In-vivo studies were performed on KK-a/y mice given the
      extract for 6 weeks. Insulin tolerance test was performed, and relative
      pancreatic islets area was measured. Mechanisms of action were investigated in L6
      myotubes using protein array, Western blot analysis and confocal microscopy.
      Glucose uptake assays were performed in 3T3-L1 adipocytes. RESULTS: Sarcopoterium
      spinosum extract reduced fasting blood glucose and improved insulin sensitivity
      in treated mice. Hypertrophic islets were detected in diabetic, but not in
      Sarcopoterium spinosum-treated mice. Sarcopoterium spinosum phosphorylated PTEN
      on ser380 and thr382/383, which are known inhibitory sites. PKB was not
      phosphorylated by Sarcopoterium spinosum, however, translocation of PKB from
      cytoplasm to the membrane and nucleus was detected. Target proteins of PKB were
      regulated by Sarcopoterium spinosum; GSK3beta was phosphorylated and cytosolic
      localization of FoxO was increased. Glucose uptake was increased in a PI3K and
      AMPK-independent mechanism. CONCLUSIONS: We suggest that Sarcopoterium spinosum
      inhibited PTEN and activated PKB by a mechanism which is independent of ser473
      and thr308 phosphorylation. Other post translation modifications might be
      involved and should be analyzed further in order to understand this unique PKB
      activation. Identifying the active molecules in the extract, may lead to the
      development of new agents for the treatment of insulin resistance.

PMID- 24882729
TI  - Anti-inflammatory effects of ethanol extracts of Chinese propolis and buds from
      poplar (Populus*canadensis).
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Propolis is used widely in a number of cultures
      as a folk medicine and is gaining wider recognition for its potential therapeutic
      use, due to its wide range of biological properties and pharmacological
      activities, especially its anti-inflammatory effects. Despite an increasing
      number of studies focused on the biological activities of propolis together with
      its botanical sources, studies on Chinese propolis are insufficient. This study
      was designed to investigate the anti-inflammatory properties of ethanol extracts
      from Chinese propolis (EECP) and poplar buds (EEPB) from Populus*canadensis
      Moench (Salicaceae family). MATERIALS AND METHODS: Phytochemical analysis of EECP
      and EEPB was performed via total phenolic and flavonoid content measurements
      followed by high-performance liquid chromatography (HPLC) analysis. DPPH and ABTS
      free-radical scavenging methods were used to evaluate their anti-oxidant
      properties. The anti-inflammatory effects of EECP and EEPB were investigated in
      vitro by evaluating their modulating effects on the key inflammatory cytokines
      and mediators in LPS/IFN-gamma co-stimulated RAW 264.7 cells and by measuring
      nuclear factor (NF)-kappaB activation in TNF-alpha or IL-1beta stimulation HEK
      293 cells using reporter gene assays. Their effects on acute inflammatory
      symptoms (LPS-induced endotoxemia and acute pulmonary damage) were also examined
      in mice. RESULTS: EECP and EEPB exhibited strong free-radical scavenging activity
      and significant in vitro anti-inflammatory effects by modulating key inflammatory
      mediators of mRNA transcription, inhibiting the production of specific
      inflammatory cytokines, and blocking the activation of nuclear factor (NF)
      kappaB. The administration of EECP and EEPB (25 and 100 mg/kg) provided
      significant protective effects by attenuating lung histopathological changes and
      suppressing the secretion of LPS-stimulated inflammatory cytokines, such as
      interleukin-6 (IL-6), IL-10, MCP-1, TNF-alpha and IL-12p70 production in
      endotoxemic mice. CONCLUSIONS: The results presented here reveal the potent anti
      inflammatory properties of Chinese propolis and poplar buds, and provide
      biological information for developing suitable substitute(s) for propolis in the
      prevention and treatment of inflammatory diseases.

PMID- 24882730
TI  - Mirabijalone E: a novel rotenoid from Mirabilis himalaica inhibited A549 cell
      growth in vitro and in vivo.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The roots of Mirabilis himalaica have been used
      in Tibetan folk medicine for treatment of uterine cancer, nephritis edematous,
      renal calculus and arthrodynia. In our previous work, the ethanol extract of
      roots had shown potent cytotoxicity against human cancer cells. However, no
      information is available on the antitumor effect of Mirabilis himalaica. The aim
      of the present study was to investigate the active constituents guided by
      bioassay and evaluate the related antitumor efficacy in vitro and in vivo.
      MATERIALS AND METHODS: The active subextract (ethyl acetate) was subjected to
      successive chemical separation using a combination of silica gel, LH-20
      chromatography and semi-preparative HPLC. The structures were determined by
      spectroscopic analysis techniques such as nuclear magnetic resonance (NMR) and
      mass spectrometry. Three human cancer cell lines, A549, HepG2 and HeLa were used
      for in vitro cytotoxicity evaluation of all isolated compounds by MTT-assay.
      Then, the potent and novel compound mirabijalone E was employed to the mechanism
      study againstA549 cells. BrdU immunofluorescence, soft agar assay and cell cycle
      analysis were employed to detect the cell proliferation effects. Annexin V
      FITC/PI staining assay was used for examining apoptotic effects. Expression
      levels of apoptosis-related proteins were determined by western blot assay. in
      vivo tumorigenic assay was used to evaluate the xenograft tumor growth treated
      with mirabijalone E. RESULTS: One new rotenoid compound, mirabijalone E, together
      with eight known rotenoids was isolated from Mirabilis himalaica. Mirabijalone E,
      9-O-methyl-inone B, boeravinone C and boeravinone H exhibited cytotoxicity
      against A 549 and HeLa cells. Further study on mirabijalone E was carried out in
      vitro and in vivo. Mirabijalone E inhibited A549 cells growth in a time and dose
      dependent manner, which arrested cell cycle in S phase. Mechanistically,
      mirabijalone E treatment resulted in the increase of Bax expression level, the
      decrease of Bcl-2 level and the activation of caspase-3, which suggested the
      activation of apoptosis cascades. Consequently, the xenograft treated with
      mirabijalone E showed markedly suppressed tumor growth. CONCLUSIONS: The result
      suggested that mirabijalone E, together with active compounds, 9-O-methyl-4
      hydroxyboeravinone B, boeravinone C and boeravinone H could be a promising
      candidate for cancer therapy.

PMID- 24882732
TI  - Ethnobotanical uses of medicinal plants in the highlands of Soan Valley, Salt
      Range, Pakistan.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Two thirds of the world's population relies on
      medicinal plants for centuries for several human pathologies. Present study aimed
      to identify, catalogue and document the large number of medicinal plants used in
      traditional medicine in Soan Valley, Salt Range, Pakistan. MATERIALS AND METHODS:
      Informal interviews were conducted involving a total of 255 villagers (155 male
      and 65 female and 35 herbalists) to elicit the knowledge and use of medicinal
      plants. RESULTS: Local communities possessed knowledge of fifty eight (58)
      medicinal plant species belonging to thirty five (35) families to treat fifteen
      ailment categories. Whole plant and leaves were the most frequently used plant
      parts (24%) followed by seed (14%), root (12%), flower (7%), bulb (6%), fruit
      (4%), stem (3%), latex and rhizome (2%) and sap and gum (1%). Frequently used
      growth forms of medicinal plants were wild herbs (63%) followed by cultivated
      herbs (14%), wild trees (11%), wild shrubs (10%) and wild and cultivated herbs
      (2%). Preparations were administrated generally through oral and topical routes.
      Local people were familiar mostly with the species in order to deal common
      ailments particularly cough, cold, digestive problems, fever, headache, and skin
      infections. Complex ailments were treated by traditional healers. Justica
      adhatoda, Olea ferruginea, Amaranthus viridis and Mentha royleana were identified
      as plants with high use value (UV). CONCLUSIONS: This study revealed that the
      area harbors high diversity of medicinal flora. Despite gradual socio-cultural
      transformation, local communities still hold ample knowledge of plants and their
      uses. The reliance on traditional medicines was associated with the lack of
      modern health care facilities, poverty and the traditional belief of their
      effectiveness. Medicinal plants play a significant role in management of various
      human diseases in the study area. A high degree of consensus among the informants
      was an indicative that plant use and knowledge were still strong, and
      preservation of this knowledge showed good foresight in the future. Awareness was
      thus needed to be raised among local people on sustainable utilization and
      management of plant resources.

PMID- 24882731
TI  - Long-term administration of Greek Royal Jelly improves spatial memory and
      influences the concentration of brain neurotransmitters in naturally aged Wistar
      male rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Royal Jelly (RJ) is a bee-derived product that
      has been traditionally used in the European and Asian systems of medicine for
      longevity. RJ has various pharmacological activities that may prevent aging e.g.,
      anti-inflammatory, anti-oxidative, anti-hypercholesterolemic and anti
      hyperglycemic properties. AIM OF THE STUDY: To evaluate the behavioral and
      neurochemical effects of long-term oral, previously chemically analyzed, Greek RJ
      administration to aged rats. MATERIALS AND METHODS: RJ powder was given to 18
      month old male Wistar rats (50 and 100mg of powder/kg b.w./day) by gastric gavage
      for 2 months. The spatial memory was assessed in the water maze and next the
      level of neurotransmitters, their metabolites and utilization in the selected
      brain regions were estimated. RESULTS: The improvement of memory in rats
      pretreated with the smaller dose of RJ was observed compared with controls. In
      biochemical examination mainly the depletion of dopamine and serotonin in the
      prefrontal cortex along with an increase in their metabolite concentration and
      turnover were seen. CONCLUSION: Better cognitive performance in the old animals
      using a non-toxic, natural food product in the view of the process of the aging
      of human population is noteworthy. Our results contribute towards validation of
      the traditional use of RJ in promoting a better quality of life in old age.

PMID- 24882733
TI  - Ceramide-lipid interactions studied by MD simulations and solid-state NMR.
AB  - Ceramides play a key modulatory role in many cellular processes, which results
      from their effect on the structure and dynamics of biological membranes. In this
      study, we investigate the influence of C16-ceramide (C16) on the biophysical
      properties of DMPC lipid bilayers using solid-state NMR and atomistic molecular
      dynamics (MD) simulations. MD simulations and NMR measurements were carried out
      for a pure DMPC bilayer and for a 20% DMPC-C16 mixture. Calculated key structural
      properties, namely area per lipid, chain order parameters, and mass density
      profiles, indicate that C16 has an ordering effect on the DMPC bilayer.
      Furthermore, the simulations predict that specific hydrogen-bonds form between
      DMPC and C16 molecules. Multi-nuclear solid-state NMR was used to verify these
      theoretical predictions. Chain order parameters extracted from (13)C(1)H dipole
      couplings were measured for both lipid and ceramide and follow the trend
      suggested by the MD simulations. Furthermore, (1)H-MAS NMR experiments showed a
      direct contact between ceramide and lipids. 

PMID- 24882735
TI  - Mineralizing surface is the main target of mechanical stimulation independent of
      age: 3D dynamic in vivo morphometry.
AB  - Mechanical loading can increase cortical bone mass by shifting the balance
      between bone formation and resorption towards increased formation. With advancing
      age resorption outpaces formation resulting in a net loss in cortical bone mass.
      How cortical bone (re)modeling - especially resorption - responds to mechanical
      loading with aging remains unclear. In this study, we investigated age-related
      changes in the modulation of cortical bone formation and resorption sites by
      mechanical loading. Using in vivo microCT we determined the kinetics of three
      dimensional formation and resorption parameters. To analyze age-associated
      adaptation, the left tibiae of young, adult and elderly female C57BL/6 mice were
      cyclically loaded for 2weeks. Our data showed that in the nonloaded limbs,
      cortical bone loss with age is the result of an imbalance of resorption to
      formation thickness, while the surface of resorption is comparable to formation.
      Loading has a much stronger effect on formation than on resorption; more
      specifically this effect is due to an increase in formation surface with
      mechanical stimulation. This is the only effect of loading which is conserved
      into old age. The resorption thickness is independent of loading in all age
      groups. Using this novel image analysis technique, we were able for the first
      time to quantify age-related changes in cortical (re)modeling and the adaptive
      capacity to mechanics. Most likely a therapy against age-related bone loss
      combining physical exercise and pharmaceuticals is most efficient if they each
      act on different parameters of the (re)modeling process. Despite some differences
      in skeletal aging between mice and humans, our results would suggest that
      physical exercise in old individuals can positively influence only the formation
      side of (re) modeling. 

PMID- 24882737
TI  - Amplified spontaneous emission and lasing in colloidal nanoplatelets.
AB  - Colloidal nanoplatelets (NPLs) have recently emerged as favorable light-emitting
      materials, which also show great potential as optical gain media due to their
      remarkable optical properties. In this work, we systematically investigate the
      optical gain performance of CdSe core and CdSe/CdS core/crown NPLs having
      different CdS crown size with one- and two-photon absorption pumping. The
      core/crown NPLs exhibit enhanced gain performance as compared to the core-only
      NPLs due to increased absorption cross section and the efficient interexciton
      funneling, which is from the CdS crown to the CdSe core. One- and two-photon
      absorption pumped amplified spontaneous emission thresholds are found as low as
      41 MUJ/cm(2) and 4.48 mJ/cm(2), respectively. These thresholds surpass the best
      reported optical gain performance of the state-of-the-art colloidal nanocrystals
      (i.e., quantum dots, nanorods, etc.) emitting in the same spectral range as the
      NPLs. Moreover, gain coefficient of the NPLs is measured as high as 650 cm(-1),
      which is 4-fold larger than the best reported gain coefficient of the colloidal
      quantum dots. Finally, we demonstrate a two-photon absorption pumped vertical
      cavity surface emitting laser of the NPLs with a lasing threshold as low as 2.49
      mJ/cm(2). These excellent results are attributed to the superior properties of
      the NPLs as optical gain media. 

PMID- 24882734
TI  - Anorexia nervosa and bone metabolism.
AB  - Anorexia nervosa (AN) is a psychiatric disorder characterized by self-induced
      starvation with a lifetime prevalence of 2.2% in women. The most common medical
      co-morbidity in women with AN is bone loss, with over 85% of women having bone
      mineral density values more than one standard deviation below an age comparable
      mean. The low bone mass in AN is due to multiple hormonal adaptations to under
      nutrition, including hypothalamic amenorrhea and growth hormone resistance.
      Importantly, this low bone mass is also associated with a seven-fold increased
      risk of fracture. Therefore, strategies to effectively prevent bone loss and
      increase bone mass are critical. We will review hormonal adaptations that
      contribute to bone loss in this population as well as promising new therapies
      that may increase bone mass and reduce fracture risk in AN. 

PMID- 24882738
TI  - A biphasic multiscale study of the mechanical microenvironment of chondrocytes
      within articular cartilage under unconfined compression.
AB  - Computational analyses have been used to study the biomechanical microenvironment
      of the chondrocyte that cannot be assessed by in vitro experimental studies; yet
      all computational studies thus far have focused on the effect of zonal location
      (superficial, middle, and deep) on the mechanical microenvironment of
      chondrocytes. The aim of this paper was to study the effect of both zonal and
      radial locations on the biomechanical microenvironment of chondrocytes in
      inhomogeneous cartilage under unconfined stress relaxation. A biphasic multiscale
      approach was employed and nine chondrocytes in different locations were studied.
      Hyperelastic biphasic theory and depth-dependent aggregate modulus and
      permeability of articular cartilage were included in the models. It was found
      that both zonal and radial locations affected the biomechanical stresses and
      strains of the chondrocytes. Chondrocytes in the mid-radial location had
      increased volume during the early stage of the loading process. Maximum principal
      shear stress at the interface between the chondrocyte and the extracellular
      matrix (ECM) increased with depth, yet that at the ECM-pericellular matrix (PCM)
      interface had an inverse trend. Fluid pressure decreased with depth, while the
      fluid pressure difference between the top and bottom boundaries of the microscale
      model increased with depth. Regardless of location, fluid was exchanged between
      the chondrocyte, PCM, and ECM. These findings suggested that even under simple
      compressive loading conditions, the biomechanical microenvironment of the
      chondrocytes, PCM and ECM was spatially dependent. The current study provides new
      insight on chondrocyte biomechanics. 

PMID- 24882739
TI  - Mechanical analysis of a rodent segmental bone defect model: the effects of
      internal fixation and implant stiffness on load transfer.
AB  - Segmental bone defect animal models are often used for evaluating the bone
      regeneration performance of bone substituting biomaterials. Since bone
      regeneration is dependent on mechanical loading, it is important to determine
      mechanical load transfer after stabilization of the defect and to study the
      effects of biomaterial stiffness on the transmitted load. In this study, we
      assess the mechanical load transmitted over a 6mm femur defect that is stabilized
      with an internal PEEK fixation plate. Subsequently, three types of selective
      laser melted porous titanium implants with different stiffness values were used
      to graft the defect (five specimens per group). In one additional group, the
      defect was left empty. Micro strain gauges were used to measure strain values at
      four different locations of the fixation plate during external loading on the
      femoral head. The load sharing between the fixation plate and titanium implant
      was highly variable with standard deviations of measured strain values between 31
      and 93% of the mean values. As a consequence, no significant differences were
      measured between the forces transmitted through the titanium implants with
      different elastic moduli. Only some non-significant trends were observed in the
      mean strain values that, consistent with the results of a previous finite element
      study, implied the force transmitted through the implant increases with the
      implant stiffness. The applied internal fixation method does not standardize
      mechanical loading over the defect to enable detecting small differences in bone
      regeneration performances of bone substituting biomaterials. In conclusion, the
      fixation method requires further optimization to reduce the effects of the
      operative procedure and make the mechanical loading more consistent and improve
      the overall sensitivity of this rat femur defect model. 

PMID- 24882736
TI  - Megakaryocytes are mechanically responsive and influence osteoblast proliferation
      and differentiation.
AB  - Maintenance of bone mass and geometry is influenced by mechanical stimuli.
      Paradigms suggest that osteocytes embedded within the mineralized matrix and
      osteoblasts on the bone surfaces are the primary responders to physical forces.
      However, other cells within the bone marrow cavity, such as megakaryocytes (MKs),
      are also subject to mechanical forces. Recent studies have highlighted the potent
      effects of MKs on osteoblast proliferation as well as bone formation in vivo. We
      hypothesize that MKs are capable of responding to physical forces and that the
      interactions between these cells and osteoblasts can be influenced by mechanical
      stimulation. In this study, we demonstrate that two MK cell lines respond to
      fluid shear stress in culture. Furthermore, using laser capture microdissection,
      we isolated MKs from histologic sections of murine tibiae that were exposed to
      compressive loads in vivo. C-fos, a transcription factor shown to be upregulated
      in response to load in various tissue types, was increased in MKs from loaded
      relative to non-loaded limbs at a level comparable to that of osteocytes from the
      same limbs. We also developed a co-culture system to address whether mechanical
      stimulation of MKs in culture would impact osteoblast proliferation and
      differentiation. The presence of MKs in co-culture, but not conditioned media,
      had dramatic effects on proliferation of preosteoblast MC3T3-E1 cells in culture.
      Our data suggests a minimal decrease in proliferation as well as an increase in
      mineralization capacity of osteoblasts co-cultured with MKs exposed to shear
      compared to co-cultures with unstimulated MKs. 

PMID- 24882742
TI  - Facile synthesis of intense green light emitting LiGdF4:Yb,Er-based upconversion
      bipyramidal nanocrystals and their polymer composites.
AB  - A pathway for achieving intense green light emitting LiGdF4:Yb,Er upconversion
      nanophosphors (UCNPs) via Y(3+) doping is demonstrated. It was revealed that
      Y(3+) doping initiated the formation of a tetragonal phase and affected the
      particle size. Single tetragonal-phase LiGd0.4Y0.4F4:Yb(18%),Er(2%)
      (LGY0.4F:Yb,Er) UCNPs exhibited strong upconversion (UC) green luminescence and
      tetragonal bipyramidal morphologies. They showed 1325 and 325-fold higher
      photoluminescence intensity than the 0 and 80 mol% Y(3+)-doped LiGdF4:Yb,Er
      UCNPs, respectively. Additionally the particle size (edge length) of LiGdF4:Yb,Er
      based upconversion tetragonal bipyramids (UCTBs) was controlled from 60.5 nm to
      an ultrasmall size of 9.3 nm with varying Y(3+) doping concentration. In an
      LGY0.4F:Yb,Er UCTB, uniform distribution of all constituent elements was directly
      confirmed by using high-angle annular dark-field scanning transmission electron
      microscopy and energy-filtered transmission electron microscopy (EFTEM) image
      analyses. In particular, existence of activator Er(3+) ions with extremely small
      quantity was clearly seen over a particle on the EFTEM image. Moreover, the
      LGY0.4F:Yb,Er UCTBs were successfully incorporated into the polydimethylsiloxane
      (PDMS) polymer and the highly transparent UCTB-PDMS composites showed bright
      green light under the excitation of 980 nm infrared light. 

PMID- 24882741
TI  - Assessing direct and indirect airway hyperresponsiveness in children using
      impulse oscillometry.
AB  - BACKGROUND: Airway hyperresponsiveness (AHR) is a hallmark of asthma but its
      assessment is usually restricted to older children who are capable of performing
      the maneuvers involved in spirometry. In younger children, a feasible option to
      perform the lung function measurement is impulse oscillometry (IOS), which
      requires less cooperation. OBJECTIVE: To evaluate whether assessment of AHR by
      IOS could differentiate children with various obstructive symptoms from one
      another. METHODS: One hundred twenty-one children (median age 6.0 years, range
      3.7-8.1 years) were examined: 31 with probable asthma characterized by current
      troublesome lung symptoms, 61 with a history of early wheezing disorder
      (recurrent wheezing <=24 months of age), 15 with a history of bronchopulmonary
      dysplasia, and 14 healthy controls. Indirect AHR was assessed by exercise and
      mannitol challenge tests, and direct AHR was assessed with methacholine using
      IOS. AHR to exercise was defined as an increase of at least 40% in respiratory
      resistance at 5 Hz. In the mannitol and methacholine challenges, the dose causing
      an increase of 40% in respiratory resistance at 5 Hz was calculated. RESULTS: AHR
      to exercise was good at differentiating children with current troublesome lung
      symptoms from those in the other groups (P < .001). AHR to methacholine separated
      children with current troublesome lung symptoms, early wheezing disorder, and
      bronchopulmonary dysplasia from the controls (P < .001), whereas the mannitol
      test did not distinguish among the study groups (P = .209). CONCLUSION: The
      methacholine and exercise challenge tests with IOS identify children with
      probable asthma characterized by troublesome lung symptoms and therefore may
      represent a practical aid in the evaluation of AHR in young children.

PMID- 24882740
TI  - Predicting surface strains at the human distal radius during an in vivo loading
      task--finite element model validation and application.
AB  - Bone strains resulting from physical activity are thought to be a primary driver
      of bone adaptation, but cannot be directly noninvasively measured. Because bone
      adapts nonuniformly, physical activity may make an important independent
      structural contribution to bone strength that is independent of bone mass and
      density. Our objective was to create and validate methods for subject-specific
      finite element (FE) model generation that would accurately predict the surface
      strains experienced by the distal radius during an in vivo loading task, and to
      apply these methods to a group of 23 women aged 23-35 to examine variations in
      strain, bone mass and density, and physical activity. Four cadaveric specimens
      were experimentally tested and specimen-specific FE models were developed to
      accurately predict periosteal surface strains (root mean square error=16.3%). In
      the living subjects, when 300 N load was simulated, mean strains were
      significantly inversely correlated with BMC (r=-0.893), BMD (r=-0.892) and
      physical activity level (r=-0.470). Although the group of subjects was relatively
      homogenous, BMD varied by two-fold (range: 0.19-0.40 g/cm(3)) and mean energy
      equivalent strain varied by almost six-fold (range: 226.79-1328.41 MUepsilon)
      with a simulated 300 N load. In summary, we have validated methods for estimating
      surface strains in the distal radius that occur while leaning onto the palm of
      the hand. In our subjects, strain varied widely across individuals, and was
      inversely related to bone parameters that can be measured using clinical CT, and
      inversely related to physical activity history.

PMID- 24882743
TI  - Combined newborn screening for familial hemophagocytic lymphohistiocytosis and
      severe T- and B-cell immunodeficiencies.

PMID- 24882744
TI  - Crystal cryocooling distorts conformational heterogeneity in a model Michaelis
      complex of DHFR.
AB  - Most macromolecular X-ray structures are determined from cryocooled crystals, but
      it is unclear whether cryocooling distorts functionally relevant flexibility.
      Here we compare independently acquired pairs of high-resolution data sets of a
      model Michaelis complex of dihydrofolate reductase (DHFR), collected by separate
      groups at both room and cryogenic temperatures. These data sets allow us to
      isolate the differences between experimental procedures and between temperatures.
      Our analyses of multiconformer models and time-averaged ensembles suggest that
      cryocooling suppresses and otherwise modifies side-chain and main-chain
      conformational heterogeneity, quenching dynamic contact networks. Despite some
      idiosyncratic differences, most changes from room temperature to cryogenic
      temperature are conserved and likely reflect temperature-dependent solvent
      remodeling. Both cryogenic data sets point to additional conformations not
      evident in the corresponding room temperature data sets, suggesting that
      cryocooling does not merely trap preexisting conformational heterogeneity. Our
      results demonstrate that crystal cryocooling consistently distorts the energy
      landscape of DHFR, a paragon for understanding functional protein dynamics. 

PMID- 24882746
TI  - Structural and mechanistic paradigm of leptin receptor activation revealed by
      complexes with wild-type and antagonist leptins.
AB  - Leptin activates its cognate receptor (LR) to regulate body weight and
      metabolically costly processes, such as reproduction and immune responses.
      Despite such benevolent pleiotropy, leptin-mediated signaling has been implicated
      in autoimmune diseases and breast cancer, thereby rejuvenating interest in leptin
      antagonism. We present comparative biochemical and structural studies of the LR
      ectodomain (LRecto) in complex with wild-type and antagonist leptin variants. We
      show that high-affinity binding of leptin to the cytokine receptor homology 2
      domain of LRecto primes interactions with the Ig-domain (LRIg) of another leptin
      bound LRecto to establish a quaternary assembly. In contrast, antagonist leptin
      variants carrying mutations at the LRIg binding site only enable binary complexes
      with LRecto. Acetylation of free cysteines in LRecto also abrogates quaternary
      complexes, suggesting a functional role for intrareceptor disulfides. We propose
      a revised conceptual framework for LR activation whereby leptin activates
      predimerized LR at the cell surface to seed higher order complexes with 4:4
      stoichiometry. 

PMID- 24882745
TI  - Functional conformations for pyruvate carboxylase during catalysis explored by
      cryoelectron microscopy.
AB  - The tetrameric enzyme pyruvate carboxylase (PC), a biotin-dependent carboxylase,
      produces oxaloacetate by two consecutive reactions that take place in distant
      active sites. Previous crystal structures revealed two different configurations
      for PC tetramers, the so-called symmetric and asymmetric, which were understood
      as characteristic molecular architectures for PC from different organisms. We
      have analyzed PC samples from Staphylococcus aureus while the enzyme generates
      oxaloacetate, expecting PC tetramers to display the conformational landscape
      relevant for its functioning. Using cryoelectron microscopy (cryo-EM) and sorting
      techniques, we detect previously defined symmetric and asymmetric architectures,
      demonstrating that PC maps both arrangements by large conformational changes.
      Furthermore, we observe that each configuration is coupled to one of the two
      consecutive enzymatic reactions. The findings describe the structural transitions
      relevant for the allosteric control of the multifunctional PC and demonstrate
      that by cryo-EM and classification, we can characterize freely working
      macromolecules. 

PMID- 24882748
TI  - Polarization enhancement technique for nuclear quadrupole resonance detection.
AB  - We demonstrate a dramatic increase in the signal-to-noise ratio (SNR) of a
      nuclear quadrupole resonance (NQR) signal by using a polarization enhancement
      technique. By first applying a static magnetic field to pre-polarize one spin
      subsystem of a material, and then allowing that net polarization to be
      transferred to the quadrupole subsystem, we increased the SNR of a sample of
      ammonium nitrate by one-order of magnitude. 

PMID- 24882747
TI  - Investigation of the 8-hydroxy-2'-deoxyguanosine, total antioxidant and nitric
      oxide levels of serum in dogs infected with Babesia vogeli.
AB  - Oxidative stress was defined as corruption of balance between oxidant-antioxidant
      states in favor of oxidants. In this study, it was aimed to determine oxidative
      stress in naturally infected dogs with Babesia vogeli. The 8-hydroxy-2'
      deoxyguanosine (8-OHdG), nitric oxide (NO) and total antioxidant capacity (TAC)
      levels in the sera were analyzed by ELISA. 8-OHdG levels increased in B. vogeli
      infected dogs compared to control group (P<0.05). Also, NO levels increased while
      TOC levels decreased in B. vogeli infected dogs but these variations were not
      found as statistically important (P>0.05). 

PMID- 24882750
TI  - Exacerbation of audiovestibular symptoms in a patient with Meniere's disease and
      choroidal melanoma.
AB  - We report the case of a man affected by a unilateral Meniere's disease who, after
      being free from vertigo spells and tinnitus for more than ten years, manifested
      an exacerbation of symptoms just before the diagnosis of a choroidal melanoma.
      Melanoma is an aggressive form of cancer derived from neuroectodermal
      melanocytes. Melanocytes are present in the inner ear where they contribute to
      the production of endolymphatic potentials and to the maintenance of normal
      volumes of the inner ear fluids. A possible autoimmune connection between the
      exacerbation of audiovestibular symptoms and melanoma is discussed. 

PMID- 24882749
TI  - Clinically isolated syndrome manifested as acute vestibular syndrome: bedside
      neuro-otological examination and suppression of transient evoked otoacoustic
      emissions in the differential diagnosis.
AB  - A case of a 34-year old woman with acute vestibular syndrome caused by a
      demyelinating lesion in the root entry zone of the 8th cranial nerve is
      presented. Neuro-otological bedside examination and suppression of transient
      evoked otoacoustic emissions provided objective clinical evidence of a
      retrolabyrinthine lesion. Magnetic resonance imaging and the presence of
      oligoclonal IgG bands in cerebrospinal fluid analysis established the diagnosis
      of clinically isolated syndrome. This case report highlights the clinical
      information provided by the neuro-otologist in the differential diagnosis of the
      acute vestibular syndrome and the diagnosis of possible multiple sclerosis. 

PMID- 24882751
TI  - Facioscapulohumeral muscular dystrophy.
AB  - Facioscapulohumeral muscular dystrophy (FSHD) is characterized by a typical and
      asymmetric pattern of muscle involvement and disease progression. Two forms of
      FSHD, FSHD1 and FSHD2, have been identified displaying identical clinical
      phenotype but different genetic and epigenetic basis. Autosomal dominant FSHD1
      (95% of patients) is characterized by chromatin relaxation induced by pathogenic
      contraction of a macrosatellite repeat called D4Z4 located on the 4q subtelomere
      (FSHD1 patients harbor 1 to 10 D4Z4 repeated units). Chromatin relaxation is
      associated with inappropriate expression of DUX4, a retrogene, which in muscles
      induces apoptosis and inflammation. Consistent with this hypothesis, individuals
      carrying zero repeat on chromosome 4 do not develop FSHD1. Not all D4Z4
      contracted alleles cause FSHD. Distal to the last D4Z4 unit, a polymorphic site
      with two allelic variants has been identified: 4qA and 4qB. 4qA is in cis with a
      functional polyadenylation consensus site. Only contractions on 4qA alleles are
      pathogenic because the DUX4 transcript is polyadenylated and translated into
      stable protein. FSHD2 is instead a digenic disease. Chromatin relaxation of the
      D4Z4 locus is caused by heterozygous mutations in the SMCHD1 gene encoding a
      protein essential for chromatin condensation. These patients also harbor at least
      one 4qA allele in order to express stable DUX4 transcripts. FSHD1 and FSHD2 may
      have an additive effect: patients harboring D4Z4 contraction and SMCHD1 mutations
      display a more severe clinical phenotype than with either defect alone. Knowledge
      of the complex genetic and epigenetic defects causing these diseases is essential
      in view of designing novel therapeutic strategies. This article is part of a
      Special Issue entitled: Neuromuscular Diseases: Pathology and Molecular
      Pathogenesis. 

PMID- 24882752
TI  - Myotonic dystrophies: An update on clinical aspects, genetic, pathology, and
      molecular pathomechanisms.
AB  - Myotonic dystrophy (DM) is the most common adult muscular dystrophy,
      characterized by autosomal dominant progressive myopathy, myotonia and multiorgan
      involvement. To date two distinct forms caused by similar mutations have been
      identified. Myotonic dystrophy type 1 (DM1, Steinert's disease) is caused by a
      (CTG)n expansion in DMPK, while myotonic dystrophy type 2 (DM2) is caused by a
      (CCTG)n expansion in ZNF9/CNBP. When transcribed into CUG/CCUG-containing RNA,
      mutant transcripts aggregate as nuclear foci that sequester RNA-binding proteins,
      resulting in spliceopathy of downstream effector genes. However, it is now clear
      that additional pathogenic mechanism like changes in gene expression, protein
      translation and micro-RNA metabolism may also contribute to disease pathology.
      Despite clinical and genetic similarities, DM1 and DM2 are distinct disorders
      requiring different diagnostic and management strategies. This review is an
      update on the recent advances in the understanding of the molecular mechanisms
      behind myotonic dystrophies. This article is part of a Special Issue entitled:
      Neuromuscular Diseases: Pathology and Molecular Pathogenesis. 

PMID- 24882753
TI  - Pathophysiology of circulating xanthine oxidoreductase: new emerging roles for a
      multi-tasking enzyme.
AB  - The enzyme xanthine oxidoreductase (XOR) catalyses the last step of purine
      degradation in the highest uricotelic primates as a rate-limiting enzyme in
      nucleic acid catabolism. Although XOR has been studied for more than a century,
      this enzyme continues to arouse interest because its involvement in many
      pathological conditions is not completely known. XOR is highly evolutionarily
      conserved; moreover, its activity is very versatile and tuneable at multiple
      levels and generates both oxidant and anti-oxidant products. This review covers
      the basic information on XOR biology that is essential to understand its
      enzymatic role in human pathophysiology and provides a comprehensive catalogue of
      the experimental and human pathologies associated with increased serum XOR
      levels. The production of radical species by XOR oxidase activity has been
      intensively studied and evaluated in recent decades in conjunction with the
      cytotoxic consequences and tissue injuries of various pathological conditions.
      More recently, a role has emerged for the activity of endothelium-bound enzymes
      in inducing the vascular response to oxidative stress, which includes the
      regulation of pro-inflammatory and pro-thrombotic activities of endothelial
      cells. The possible physiological functions of circulating XOR and the products
      of its enzyme activity are presented here together with their implications in
      cardiovascular and metabolic diseases. 

PMID- 24882754
TI  - Autophagy and mitophagy in diabetic cardiomyopathy.
AB  - Diabetic cardiomyopathy is a heart muscle-specific disease that increases the
      risk of heart failure and mortality in diabetic patients independent of vascular
      pathology. Mitochondria are cellular power plants that generate energy for heart
      contraction and concurrently produce reactive oxygen species that, if unchecked,
      may damage the mitochondria and the heart. Elimination of damaged mitochondria by
      autophagy known as mitophagy is an essential process for maintaining normal
      cardiac function at baseline and in response to various stress and disease
      conditions. Mitochondrial structural injury and functional impairment have been
      shown to contribute to diabetic heart disease. Recent studies have demonstrated
      an inhibited autophagic flux in the hearts of diabetic animals. Surprisingly, the
      diminished autophagy appears to be an adaptive response that protects against
      cardiac injury in type 1 diabetes. This raises several questions regarding the
      relationship between general autophagy and selective mitophagy in the diabetic
      heart. However, autophagy may play a different role in the hearts of type 2
      diabetic animals. In this review, we will summarize current knowledge in this
      field and discuss the potential functional roles of autophagy and mitophagy in
      the pathogenesis of diabetic cardiomyopathy. This article is part of a Special
      Issue entitled: Autophagy and protein quality control in cardiometabolic
      diseases. 

PMID- 24882755
TI  - Rapidly expanding knowledge on the role of the gut microbiome in health and
      disease.
AB  - The human gut is colonized by a wide diversity of micro-organisms, which are now
      known to play a key role in the human host by regulating metabolic functions and
      immune homeostasis. Many studies have indicated that the genomes of our gut
      microbiota, known as the gut microbiome or our "other genome" could play an
      important role in immune-related, complex diseases, and growing evidence supports
      a causal role for gut microbiota in regulating predisposition to diseases. A
      comprehensive analysis of the human gut microbiome is thus important to unravel
      the exact mechanisms by which the gut microbiota are involved in health and
      disease. Recent advances in next-generation sequencing technology, along with the
      development of metagenomics and bioinformatics tools, have provided opportunities
      to characterize the microbial communities. Furthermore, studies using germ-free
      animals have shed light on how the gut microbiota are involved in autoimmunity.
      In this review we describe the different approaches used to characterize the
      human microbiome, review current knowledge about the gut microbiome, and discuss
      the role of gut microbiota in immune homeostasis and autoimmunity. Finally, we
      indicate how this knowledge could be used to improve human health by manipulating
      the gut microbiota. This article is part of a Special Issue entitled: From Genome
      to Function.

PMID- 24882756
TI  - [Comparative analysis of video-assisted thoracic surgery versus open resection
      for early-stage thymoma].
AB  - BACKGROUND: Video-assisted thoracic surgery (VATS) has significantly developed
      over the last decade. However, a VATS approach for thymoma remains controversial.
      The aim of this study was to evaluate the feasibility of VATS thymectomy for the
      treatment of early-stage thymoma and to compare the outcomes with open resection.
      METHODS: A comparative study of 59 patients who underwent surgical resection for
      early stage thymoma (VATS: 44 and open resection: 15) between 1993 and 2011 was
      performed. Data of patient characteristics, morbidity, mortality, length of
      hospital stay, the relationship between miasthenia gravis-thymoma, recurrence,
      and survival were collected for statistical analysis. RESULTS: Thymomas were
      classified according to Masaoka staging system: 38 in stage I (VATS group: 29 and
      open group: 9) and 21 in stage II (VATS group: 15 and open group: 6). The mean
      tumor size in the open group was 7.6cm (13-4cm) and in the VATS group 6.9cm (12
      2.5cm). The average length of stay was shorter in the VATS group than in the open
      group (P<.001). No significant differences were found in the estimated recurrence
      free and overall 5-year survival rates (96% vs. 100%) between the 2 groups.
      CONCLUSIONS: VATS thymectomy for early-stage thymoma is technically feasible and
      is associated with a shorter hospital stay. The 5-year oncologic outcomes were
      similar in the open and VATS groups.

PMID- 24882757
TI  - Adverse effects of high glucose levels on somite and limb development in avian
      embryos.
AB  - Gestational diabetes has an adverse impact on fetal musculoskeletal development,
      but the mechanism involved is still not completely understood. In this study, we
      investigated the effects of high glucose on the developing somites and their
      derivate using the chick embryo as a model. We demonstrated that under high
      glucose, the number of generated somites was reduced and their morphology altered
      in 2-day old chick embryos. In addition, high glucose repressed the development
      of the limb buds in 5.5-day old chick embryos. We also demonstrated that high
      glucose abridged the development of the sclerotome and the cartilage in the
      developing limb bud. The sonic hedgehog (Shh) gene has been reported to play a
      crucial role in the development and differentiation of sclerotome. Hence, we
      examined how Shh expression in the sclerotome was affected under high glucose. We
      found that high glucose treatment significantly inhibited Shh expression. The
      high glucose also impaired myotome formation at trunk level - as revealed by
      immunofluorescent staining with MF20 antibodies. In the neural tube, we
      established that Wnt3a expression was also significantly repressed. In summary,
      our study demonstrates that high glucose concentrations impair somite and limb
      bud development in chick embryos, and suggests that Shh and Wnt genes may play a
      role in the underlying mechanism. 

PMID- 24882758
TI  - Screening level health risk assessment of selected metals in apple juice sold in
      the United States.
AB  - Concerns have recently been raised about the presence of metals in apple juices.
      As such, the concentration of aluminum (Al), arsenic (As), cadmium (Cd), chromium
      (Cr), copper (Cu), lead (Pb), manganese (Mn), mercury (Hg), and zinc (Zn) were
      measured in six commercially available brands of apple juice and three organic
      brands. The concentrations of total As, Cd, Cr, Cu, Hg, and Zn in all nine apple
      juice brands sampled were below each metal's respective U.S. Food and Drug
      Administration (FDA) maximum contaminant level for bottled water. However, in
      some apple juices the levels of Al, Pb, and Mn exceeded FDA maximum contaminant
      levels for bottled water. Therefore, a screening level risk assessment was
      carried out to assess the potential non-carcinogenic and carcinogenic risks that
      may result from metal exposure via apple juice consumption. Changes in blood Pb
      concentrations were also estimated to characterize potential risk from Pb
      exposure. Our results suggest that the exposure concentrations of the studied
      metals do not pose an increased non-carcinogenic risk (Hazard Index<1).
      Incremental lifetime cancer risk (ILCR) resulting from apple juice consumption
      was also estimated using both the California Office of Environmental Health
      Hazard Assessment (OEHHA) and the U.S. EPA cancer slope factor for inorganic As. 

PMID- 24882759
TI  - Exosomes mediate intercellular transfer of pro-fibrogenic connective tissue
      growth factor (CCN2) between hepatic stellate cells, the principal fibrotic cells
      in the liver.
AB  - BACKGROUND: Fibrogenic pathways in the liver are principally regulated by hepatic
      stellate cells (HSC), which produce and respond to fibrotic mediators such as
      connective tissue growth factor (CCN2). The aim of this study was to determine
      whether CCN2 is shuttled between HSC in membranous nanovesicles, or "exosomes."
      METHODS: Exosomes were incubated with HSC after isolation from conditioned medium
      of control or CCN2-green fluorescent protein (GFP)-transfected primary mouse HSC
      or human LX-2 HSC. Some exosomes were stained fluorescently with PKH26. HSC co
      culture experiments were performed in the presence of GW4869 exosome inhibitor.
      CCN2 or CCN2-GFP were evaluated by quantitative real-time polymerase chain
      reaction or Western blot. RESULTS: HSC-derived exosomes contained CCN2 or CCN2
      mRNA, each of which increased in concentration during HSC activation or after
      transfection of HSC with CCN2-GFP. Exosomes, stained with either PKH26 or
      purified from CCN2-GFP-transfected cells, were taken up by activated or quiescent
      HSC resulting in CCN2-GFP delivery, as shown by their direct addition to
      recipient cells or by the GW4869-dependency of donor HSC. CONCLUSION: CCN2 is
      packaged into secreted, nano-sized exosomes that mediate its intercellular
      transfer between HSC. Exosomal CCN2 may amplify or fine tune fibrogenic signaling
      and, in conjunction with other exosome constituents, may have utility as a
      noninvasive biomarker to assess hepatic fibrosis.

PMID- 24882760
TI  - Activated clotting time of thrombelastography (T-ACT) predicts early postinjury
      blood component transfusion beyond plasma.
AB  - INTRODUCTION: Rapid thrombelastography (rTEG) has been advocated as a point-of
      care test to manage trauma-induced coagulopathy. rTEG activated clotting time (T
      ACT) results become available much sooner than other rTEG values, thus offering
      an attractive tool to guide blood component transfusion in a hemorrhagic shock.
      We hypothesize that patients with a prolonged T-ACT require replacement of
      platelets (Plts) and cryoprecipitate (Cryo) in addition to plasma to correct
      trauma-induced coagulopathy. METHODS: A prospective trauma registry was reviewed
      for patients with an r-TEG available within 3 hours of injury. Blood was
      collected via a standardized protocol for rTEG. Patients were stratified into
      quartiles: low (T-ACT <113 seconds), mild (T-ACT 113-120 seconds), moderate (T
      ACT 121-140 seconds), and severe (T-ACT >140 seconds). Transfusion requirements
      were evaluated during the first 6 hours after injury. RESULTS: A total of 114
      patients were included. Median age was 39 years, injury severity score 20, base
      deficit 10, and mortality rate 13%. T-ACT cohorts had similar age (P = .11),
      injury severity score (P = .55), and base deficit (P = .38). An T-ACT >140
      seconds predicted a lower angle (median 57 vs 70, P < .000) and maximum amplitude
      (46 vs 60, P = .002), and patients received more Cryo (0.5 vs 0, P <= .000) and
      Plts (1 vs 0, P = .006). CONCLUSION: Injured patients requiring resuscitation
      with blood transfusion that have a T-ACT >140 seconds are polycoagulopathic and
      may benefit from early Cryo and Plts.

PMID- 24882761
TI  - New perspectives in the treatment of hidradenitis suppurativa (surgery and
      brewer's yeast-exclusion diet): Some clarifications.

PMID- 24882764
TI  - Twisted gastric sleeve.

PMID- 24882762
TI  - Utility of serum thyroglobulin measurements after prophylactic thyroidectomy in
      patients with hereditary medullary thyroid cancer.
AB  - INTRODUCTION: Prophylactic thyroidectomy can be curative for patients with
      hereditary medullary thyroid cancer (MTC) caused by RET proto-oncogene mutations.
      Calcitonin is a sensitive tumor marker used to follow patients. We suggest that
      thyroglobulin (Tg) levels should also be monitored postoperatively in these
      patients. METHODS: We reviewed patients with RET mutations who underwent
      prophylactic thyroidectomy between 1981 and 2011 at an academic endocrine surgery
      center. Patients were excluded if they had no postoperative Tg levels recorded.
      RESULTS: Of the 22 patients who underwent prophylactic thyroidectomy, 14 were
      included in the final analysis. The average age at thyroidectomy was 9.8 years
      (range, 4-29). Tg levels were detectable 1.5 months to 31 years postoperatively
      in 11 patients (79%), all of whom were <15 years old at thyroidectomy. Median
      thyroid-stimulating hormone (TSH) was 2.5 mIU/L and 13.4 mIU/L in patients with
      undetectable and detectable Tg, respectively. Of those with detectable Tg, 5 had
      cervical ultrasonographic examination: Two showed no residual tissue in the
      thyroid bed, and 3 showed remnant thyroid tissue. CONCLUSION: Tg levels can
      identify patients with remnant thyroid tissue after prophylactic thyroidectomy.
      Ultrasonography can determine whether thyroid tissue remains posterolaterally
      that is at risk of MTC recurrence. Maintaining normal TSH may prevent growth of
      remaining thyroid follicular cells.

PMID- 24882765
TI  - Expanding the scholarship on leadership training in dental education.

PMID- 24882766
TI  - The impact on dental students of changes to the National Board Dental Examination
      grading system.
AB  - The purpose of this study was to assess how the change to pass/fail grading of
      the National Board Dental Examination (NBDE) Part I has impacted dental students'
      study habits and their perspectives on pursuit of postdoctoral specialty
      education. This cross-sectional survey-based study included over 75 percent of
      U.S. dental schools and a total of 1,843 responses. This sample was 18.5 percent
      of all potentially eligible U.S. dental students. Participating schools
      distributed the electronic survey to their last class to take the NBDE Part I for
      a numerical score and the first class to take the NBDE Part I pass/fail.
      Respondents who took the exam for a numerical score and were interested in a
      specialty reported studying the most (average 167 hours) compared to respondents
      who took the exam pass/fail (average 114 hours). Respondents who took the exam
      pass/fail and reported feeling that this change decreased their chances of
      getting into a specialty program outnumbered those who thought the change
      increased their chances (3:1). This study observed a correlation between the
      recent grading changes to the NBDE Part I and decreased reported study time.
      Eighty percent of the respondents preferred a standardized, objective measure to
      help differentiate them when applying to specialty programs, and the majority
      reported feeling that the change in grading practices negatively affected their
      chances of pursuing a specialty.

PMID- 24882767
TI  - Using dental students' preclinical performance as an indicator of clinical
      success.
AB  - The purpose of this study was to evaluate part of one dental school's predoctoral
      curriculum by investigating correlations between students' final grades in two
      preclinical courses and their performance in the related clinical courses. The
      sample consisted of 301 students at Tufts University School of Dental Medicine
      who graduated in 2010 and 2011. All final grades used as data were obtained from
      the Registrar's Office and evaluated anonymously. The average preclinical final
      grades differed significantly for students in the 2010 (M=84.92, SD=3.35) and
      2011 (M=79.67, SD=4.67) classes, as did their average clinical final grades
      (2010: M=88.38, SD=2.13; 2011: M=87.45, SD=2.06). The data for each class were
      therefore examined separately. Results showed that the correlation between
      students' preclinical grades and clinical grades in operative dentistry and fixed
      prosthodontics was statistically significant (2010: r(2)=0.144, p<0.001; 2011:
      r(2)=0.261, p<0.001). This finding suggests there may be a positive relationship
      between preclinical and clinical performance of these students; however, the
      discrete factors contributing to that relationship were not investigated in this
      study and require further research.

PMID- 24882768
TI  - Effective use of e-grading in the dental simulation clinic.
AB  - The purpose of this article is to describe the development and implementation of
      a grading software system, accessible from any platform, that engages today's
      generation of students and replaces paper grading. Set up at one U.S. dental
      school in an all-access, anytime (24/7) web-based program accessed through
      tablets, the software allows for a comparison between students' self-grading and
      instructor grading. This comparison facilitates student-faculty interaction,
      promoting discussion and student learning. The software can also be used for
      practical examination grading in which blinded grading between instructors is
      possible. The data gathered can produce descriptive reports students can draw
      upon to encourage self-learning and guided learning, propelling students to a
      better understanding of critical principles as they progress through multiple
      psychomotor skill sets. Other reports generated by the software allow for
      instructor calibration, exporting of grades directly into the university grading
      report system, and visual analysis of trends within each class. In a post-course
      survey, students (56 percent response rate) and faculty (79 percent response
      rate) agreed that the electronic grading was more efficient and allowed more time
      for faculty-student interaction than the previous grading system, thus creating
      an environment more conducive to learning. Overall, the software has improved
      students' perception of enhanced kinetic skills, while facilitating
      administration of preclinical projects and practical examinations.

PMID- 24882770
TI  - A survey of social media policies in U.S. dental schools.
AB  - Since social media sites began to appear in the 1990s, their popularity has
      increased dramatically, especially among younger individuals. With this
      widespread use of social media, institutions of higher education are finding the
      need to implement social media policies. The purpose of this study was to gather
      information from accredited U.S. dental schools on their social media policies. A
      survey sent to academic deans asked questions related to social media policies
      and violations of policies. The survey yielded a 35.9 percent (n=23) response
      rate. Social media policies at the university level were reported by 47.8 percent
      (n=11) of respondents, and 34.8 percent (n=8) had social media policies
      specifically in the dental school. Schools that had an institutional social media
      policy were more likely to have a social media policy in the dental school
      (p=0.01), and dental schools were more likely to have a policy if the academic
      dean had been in the position less than five years (p=0.01). All twenty-three
      responding dental schools have official social media pages. Dental educators and
      administrators may want to look for opportunities to raise awareness of social
      media professionalism in their dental schools.

PMID- 24882769
TI  - Educational technology for millennial dental hygiene students: a survey of U.S.
      dental hygiene programs.
AB  - A growing body of literature suggests that today's learners have changed and
      education must change as well since Millennial generation students expect
      technology to be used in their coursework. This study sought to determine what
      educational technology is being used in U.S. dental hygiene programs, what
      student and faculty perceptions are of the effectiveness of technology, and what
      barriers exist to implementing educational technology. A stratified random sample
      of 120 entry-level dental hygiene programs nationwide were invited to participate
      in a survey. Fourteen programs participated, yielding a pool of 415 potential
      individual participants; out of those, eighty-four student and thirty-eight
      faculty respondents were included in the analysis, a total of 122. Results were
      analyzed using descriptive statistics and a Mann-Whitney U test (p<0.05). Faculty
      and student respondents agreed on the effectiveness of educational technology in
      all areas except clickers and wikis. The faculty members tended to rate the
      effectiveness of educational technology higher than did the students. The
      greatest perceived barrier to implementing technology was technical difficulties.
      This study suggests that support services should be available to faculty and
      students to ensure successful implementation of technology. Dental hygiene
      educators have adopted many types of educational technology, but more data are
      needed to determine best practices.

PMID- 24882771
TI  - Comparing face-to-face, synchronous, and asynchronous learning: postgraduate
      dental resident preferences.
AB  - The Department of Dental Medicine of Lutheran Medical Center has developed an
      asynchronous online curriculum consisting of prerecorded PowerPoint presentations
      with audio explanations. The focus of this study was to evaluate if the new
      asynchronous format satisfied the educational needs of the residents compared to
      traditional lecture (face-to-face) and synchronous (distance learning) formats.
      Lectures were delivered to 219 dental residents employing face-to-face and
      synchronous formats, as well as the new asynchronous format; 169 (77 percent)
      participated in the study. Outcomes were assessed with pretests, posttests, and
      individual lecture surveys. Results found the residents preferred face-to-face
      and asynchronous formats to the synchronous format in terms of effectiveness and
      clarity of presentations. This preference was directly related to the residents'
      perception of how well the technology worked in each format. The residents also
      rated the quality of student-instructor and student-student interactions in the
      synchronous and asynchronous formats significantly higher after taking the
      lecture series than they did before taking it. However, they rated the face-to
      face format as significantly more conducive to student-instructor and student
      student interaction. While the study found technology had a major impact on the
      efficacy of this curricular model, the results suggest that the asynchronous
      format can be an effective way to teach a postgraduate course.

PMID- 24882763
TI  - Safety assessment of resident grade and supervision level during emergency
      appendectomy: analysis of a multicenter, prospective study.
AB  - BACKGROUND: Resident surgeons have been identified as a risk factor for worse
      outcome after appendectomy. The context of grade of resident and impact of
      supervision require further investigation. The objective of this study was to
      determine whether grade and supervision level of resident-performed appendectomy
      affects patient outcome. METHODS: A multicenter, prospective cohort study was
      performed for consecutive patients undergoing appendectomy during May and June
      2013. The primary endpoint for this analysis was the 30-day adverse event rate.
      Supervision was defined as resident-performed appendectomy with an attending
      scrubbed. Multivariable binary logistic regression was used to take into account
      case mix and produce adjusted odds ratios (OR). RESULTS: From 2,867
      appendectomies, 87% were performed by residents, and 72% were performed
      unsupervised. Residents operated on significantly younger patients with lower
      American Society of Anesthesiologists scores. Although wound infection rates were
      similar between attendings, and senior and junior residents (4.1%, 3.8%, 3.4%
      respectively; P = .486), pelvic abscess rate was greater for attendings (5.2%,
      2.7%, 2.4%; P = .045). In adjusted models, supervised senior, supervised junior,
      and unsupervised junior residents showed no difference in 30-day adverse event
      rates compared with attendings (OR, 1.07 [P = .834], 0.93 [P = .773], and 0.83 [P
      = .264] respectively); unsupervised senior residents had a lesser rate of adverse
      events (OR, 0.71; P = .045). All resident groups showed no difference for rates
      of histopathologically normal appendectomy compared with attendings. CONCLUSION:
      Resident-performed appendectomy does not worsen patient outcomes. These findings
      support independent resident operating rights for selected cases. The system
      relies on mutual credentialing of competency between residents and supervising
      attendings.

PMID- 24882772
TI  - Online cultural competency education for millennial dental students.
AB  - Teaching cultural competence is now an educational requirement for U.S. dental
      curricula to meet 2013 accreditation standards. The question now is, given time
      restrictions, limited resources, and budget constraints faced by the majority of
      dental schools, how can they provide effective cultural competency education to
      prepare future dental professionals? An additional concern regarding instruction
      is the recent focus on techniques to engage Millennial learners since this
      generation is characterized as technologically savvy with a preference for
      multimedia and general dislike of traditional lectures. With these issues in
      mind, Georgia Regents University developed Healthy Perspectives, an online,
      interactive course in cultural competence designed to engage Millennial students.
      Both before and after the course, the students were asked to complete a modified
      version of the Clinical Cultural Competency Questionnaire. Of the eighty-eight
      students in the course (eighty-one first-year dental students and seven entering
      radiology students), seventy-one completed the questionnaire both before and
      after the course, for an 81 percent response rate. Seventy-five students also
      completed the course evaluation. The pre and post questionnaires showed
      statistically significant gains for students across the four primary areas of
      self-awareness, knowledge, attitudes, and skills. Student evaluations of the
      course were generally positive, particularly regarding content, but somewhat
      surprisingly their assessment of the interactive components (which were designed
      to meet generational expectations) was ambivalent.

PMID- 24882773
TI  - Dentists' leadership-related educational experiences, attitudes, and past and
      current behavior.
AB  - The purpose of this study was to assess practicing dentists' perceptions of their
      leadership-related educational experiences during predoctoral education and after
      graduation, to investigate if these perceptions differed as a function of the
      respondents' graduation year and gender, and to explore the relationships between
      educational experiences and the respondents' understanding/perceptions of
      leadership, leadership-related attitudes, self-perceived effectiveness, and past
      and current leadership- related behavior. Of the 3,000 general dentist members of
      the American Dental Association who were invited to participate, 593 returned the
      survey for a response rate of 20 percent. Between 37 and 65 percent of the
      respondents indicated that their predoctoral dental education had not prepared
      them well on a series of factors related to being leaders in their practice,
      community, state, or at the national level. However, 33 to 77 percent of these
      dentists responded that educational experiences after graduation prepared them
      well for different types of leadership activities. Overall, respondents rated
      their predoctoral experiences significantly less positively than their
      experiences after graduation for each content area. The more recently the
      respondents had graduated, the higher they rated their leadership-related
      educational experiences. The better their educational experiences, the more
      important the respondents evaluated leadership activities in their practice,
      organized dentistry, and research/teaching, the more important they assessed
      leadership to be, and the more effective they evaluated themselves to be as
      leaders. The perceived quality of the respondents' predoctoral education was not
      correlated with their past and current leadership activities. The results of this
      study may suggest that improving leadership training during predoctoral education
      could positively affect future dentists' attitudes about leadership and ratings
      of their own effectiveness as leaders.

PMID- 24882774
TI  - Physiology education in North American dental schools: the basic science survey
      series.
AB  - As part of the Basic Science Survey Series for Dentistry, members of the American
      Dental Education Association (ADEA) Physiology, Pharmacology, and Therapeutics
      Section surveyed directors of physiology courses in North American dental
      schools. The survey was designed to assess, among other things, faculty
      affiliation and experience of course directors, teaching methods, general course
      content and emphasis, extent of interdisciplinary (shared) instruction, and
      impact of recent curricular changes. Responses were received from forty-four of
      sixty-seven (65.7 percent) U.S. and Canadian dental schools. The findings suggest
      the following: substantial variation exists in instructional hours, faculty
      affiliation, class size, and interdisciplinary nature of physiology courses;
      physiology course content emphasis is similar between schools; student contact
      hours in physiology, which have remained relatively stable in the past fifteen
      years, are starting to be reduced; recent curricular changes have often been
      directed towards enhancing the integrative and clinically relevant aspects of
      physiology instruction; and a trend toward innovative content delivery, such as
      use of computer-assisted instruction, is evident. Data from this study may be
      useful to physiology course directors, curriculum committees, and other dental
      educators with an interest in integrative and interprofessional education.

PMID- 24882775
TI  - Tobacco cessation treatment education for dental students using standardized
      patients.
AB  - The use of standardized patients (SPs) shows promise in tobacco cessation
      treatment (TCT) training by providing a simulated clinical environment for dental
      students to practice counseling skills with individuals trained to portray
      patients. The purpose of this study was to determine if there was a difference in
      attitudes, perceptions, and knowledge between dental students who received a
      lecture and practice sessions with SPs and those who received a lecture only.
      Dental students in an introductory clinical course at one dental school were
      invited to participate in the study by completing a pre and post questionnaire.
      The pre questionnaire was administered to all students prior to a tobacco
      cessation lecture. Students were group-randomized to either the intervention or
      control group. The intervention group completed the post questionnaire after the
      lecture and practice sessions with SPs, and the control group completed it after
      the lecture only. Of ninety-eight students who attended the lecture and were
      invited to participate in the study, a total of ninety-four from the two groups
      (96 percent) provided two linkable questionnaires for analysis. In the results,
      training with lecture and SPs increased the students' understanding of barriers,
      subjective norms, perceived skills, self-efficacy, and intentions to provide TCT
      more than those in the lecture only; however, it did not significantly increase
      their attitudes and knowledge. These findings suggest that using SPs is a
      valuable educational method to promote the provision of TCT by dental students
      and graduates. 

PMID- 24882776
TI  - From classroom teaching to clinical practice: experiences of senior dental
      students regarding the shortened dental arch concept.
AB  - This study explored the barriers to a meaningful translation of didactic
      classroom instruction to clinical practice, using the shortened dental arch (SDA)
      concept as a case study. A combination of survey and individual and group
      interviews (a mixed-methods approach) was used to collect data related to the
      SDA. The cohort consisted of senior dental students and their clinical teachers
      at the University of the Western Cape, South Africa. The response rates were 100
      percent for the students (n=73) and 78 percent for the clinical teachers (n=16).
      Triangulation was employed to eliminate bias and strengthen the reliability of
      the research. In the quantitative analysis, most students (81 percent) reported
      having heard about the SDA concept at the university, but their responses
      revealed an absence of clinical implementation. The students agreed that patients
      can function adequately with an SDA and agreed with presenting it as a treatment
      option to patients. In the qualitative analysis, a "change in the clinical
      requirements," "being empowered by exposing them to SDA literature," and "change
      in health policies" were recommended measures to increase implementation of the
      SDA approach clinically. The students were positive about the SDA as a treatment
      option, but the lack of adequate knowledge and encouragement in clinical
      implementation was a hindrance to its use. 

PMID- 24882777
TI  - Concepts in critical thinking applied to caries risk assessment in dental
      education.
AB  - Much progress has been made in the science of caries risk assessment and ways to
      analyze caries risk, yet dental education has seen little movement toward the
      development of frameworks to guide learning and assess critical thinking in
      caries risk assessment. In the absence of previous proactive implementation of a
      learning framework that takes the knowledge of caries risk and critically applies
      it to the patient with the succinctness demanded in the clinical setting, the
      purpose of this study was to develop a model learning framework that combines the
      science of caries risk assessment with principles of critical thinking from the
      education literature. This article also describes the implementation of that
      model at one dental school and presents some preliminary assessment data.

PMID- 24882778
TI  - Dental floss selection and its impact on evaluation of interproximal contacts in
      licensure exams.
AB  - Ideal interproximal contacts between adjacent natural teeth or dental
      restorations are a critical factor for the health of the dental-alveolar complex.
      Interproximal contact tightness is a physiological entity affected by many
      patient-related and restorative parameters. This variation poses a challenge in
      defining the "clinically acceptable" contact area tightness (CAT) and therefore
      how students and clinicians should be trained to evaluate this parameter. The
      most widely used method to evaluate interproximal contacts is to pass dental
      floss between contact areas. Candidates for licensure exams are instructed to
      check contact areas with dental floss and are advised that this will be one of
      the crucial parameters to be evaluated in the overall restoration quality. The
      purpose of this study was to evaluate a standardized interproximal contact with
      six brands of dental floss. Thirty faculty members and thirty dental students at
      one U.S. dental school evaluated the tightness of a single interproximal contact
      on a typodont. The results showed that no difference was found between CAT
      evaluations by faculty and students, whereas significant differences were found
      between different floss brands. In light of the results, it is suggested that
      licensure boards should standardize the recommendation for which floss brand
      should be used in order to avoid inconsistencies in students' preparation.

PMID- 24882779
TI  - Assessing learning styles of Saudi dental students using Kolb's Learning Style
      Inventory.
AB  - Experiential learning theory (ELT), a theory developed by David Kolb that
      considers experience to be very important for learning, classifies learners into
      four categories: Divergers, Assimilators, Convergers, and Accommodators. Kolb
      used his Learning Style Inventory (LSI) to validate ELT. Knowing the learning
      styles of students facilitates their understanding of themselves and thereby
      increases teaching efficiency. Few studies have been conducted that investigate
      learning preferences of students in the field of dentistry. This study was
      designed to distinguish learning styles among Saudi dental students and interns
      utilizing Kolb's LSI. The survey had a response rate of 62 percent (424 of 685
      dental students), but surveys with incomplete answers or errors were excluded,
      resulting in 291 usable surveys (42 percent of the student population). The
      independent variables of this study were gender, clinical experience level,
      academic achievement as measured by grade point average (GPA), and specialty
      interest. The Diverging learning style was the dominant style among those in the
      sample. While the students preferred the Assimilating style during their early
      preclinical years, they preferred the Diverging style during their later clinical
      years. No associations were found between students' learning style and their
      gender, GPA, or specialty interest. Further research is needed to support these
      findings and demonstrate the impact of learning styles on dental students'
      learning.

PMID- 24882781
TI  - The physician becomes the patient: how my breast cancer journey taught me to be a
      better doctor.
AB  - On April 1, 2013, I received the shocking news that I had Stage II breast cancer.
      Despite my medical knowledge, at the time of my diagnosis, I was unable to grasp
      the magnitude of the ordeal I would experience. However I also received an
      unexpected gift: being a patient made me a better person and a better doctor. 

PMID- 24882780
TI  - Changes in self-directed learning readiness in dental students: a mixed-methods
      study.
AB  - The purpose of this study was to identify changes in dental students' self
      directed learning (SDL) readiness during their education. Guglielmino's SDL
      readiness scale (SDLRS) was completed at admission by dental students at the
      University of Saskatchewan and at the end of each year of training. The response
      rates varied from year to year. Between twenty-seven and thirty students
      completed the questionnaire each year at admission (93-100 percent of the
      entering class). The numbers of participants were lower in succeeding years:
      numbers used for analysis ranged from eleven to twenty-six; years in which fewer
      than eleven students participated were not included in the analysis. At
      admission, the students' mean SDLRS score was 228.98 (on a scale from 58 to 290,
      with 290 the highest); this score was higher than that of the average adult
      population (214+/-25.59). There was no significant effect of years of predental
      education, prior unsuccessful applications to dental school, interview scores,
      age, or admission test scores. There was a significant drop in SDLRS scores at
      the end of the first year for most of the cohorts (p<0.001). In addition to the
      questionnaire part of the study, two instructors and five first- and second-year
      students participated in focus groups. Those results showed that the individuals
      defined SDL narrowly and had similar perceptions of curricular factors that
      affect SDL readiness. The drop in scores one year after admission and lack of
      change with increased training suggests that current educational interventions
      may require re-examination and alteration to those that promote self-direction.

PMID- 24882782
TI  - 90 degrees -flip-angle three-dimensional double-echo steady-state (3D-DESS)
      magnetic resonance imaging of the knee: isovoxel cartilage imaging at 3T.
AB  - PURPOSE: The purpose of this study was to investigate whether 3D-double echo
      steady state (3D-DESS) with improved contrast by setting the FA (Flip angle) at
      90 degrees  is useful in 3D isotropic cartilage imaging of the knee at 3T.
      MATERIALS AND METHODS: Imaging was performed in 10 healthy volunteers using 3
      methods: with 3D-DESS using FA of 25 degrees  and 90 degrees , and with true fast
      imaging with steady-state precession (True-FISP). The signal-to-noise ratio (SNR)
      of the synovial fluid and cartilage, and contrast-to-noise ratio (CNR) were
      measured, and mean values were compared. Visual assessment of artifacts was
      performed with the cartilage divided into 6 regions. RESULTS: There were no
      significant differences in synovial fluid SNR in the comparison between FA-90
      degrees  3D-DESS and True-FISP (P=0.364). A significantly higher cartilage SNR
      was observed with FA-90 degrees  3D-DESS than with True-FISP (P=0.031). There
      were no significant differences in synovial fluid-cartilage CNR between FA-90
      degrees  3D-DESS and True-FISP (P=0.892). In the evaluation of artifacts, FA-90
      degrees  3D-DESS imaging showed a significantly higher score than True-FISP
      imaging in the patella and trochlea cartilage (P<0.001, P<0.002). CONCLUSIONS: FA
      90 degrees  3D-DESS is useful in 3D isotropic cartilage imaging of the knee at
      3T.

PMID- 24882783
TI  - MRI with cardiac pacing devices - safety in clinical practice.
AB  - OBJECTIVES: The aim of this study was to introduce a single centre "real life"
      experience of performing MRI examinations in clinical practice on patients with
      cardiac pacemaker systems. Additionally, we aimed to evaluate the safety of using
      a dedicated safety protocol for these patients. MATERIALS AND METHODS: We used a
      1.5T MRI scanner to conduct 68 MRI scans of different body regions in patients
      with pacing systems. Of the cardiac devices, 32% were MR-conditional, whereas the
      remaining 68% were MR-unsafe. We recorded the functional parameters of the
      devices prior, immediately after, and approximately one month after the MRI
      scanning, and compared the device parameters to the baseline values. RESULTS: All
      MRI examinations were completed safely, and each device could be interrogated
      normally following the MRI. We observed no changes in the programmed parameters
      of the devices. For most of the participants, the distributions of the immediate
      and one-month changes in the device parameters were within 20% of the baseline
      values, although some changes approached clinically important thresholds.
      Furthermore, we observed no differences in the variable changes between MR
      conditional and MR-unsafe pacing systems, or between scans of the thorax area and
      other scanned areas. CONCLUSION: MRI in patients with MR-conditional pacing
      systems and selected MR-unsafe systems could be performed safely under strict
      conditions in this study.

PMID- 24882784
TI  - Renal masses measuring under 2 cm: pathologic outcomes and associations with MRI
      features.
AB  - PURPOSE: To evaluate pathologic outcomes and associations with MRI features in
      small renal masses measuring up to 20mm METHODS: 86 patients (61 +/- 13 years; 45
      M/41F) with 92 renal masses measuring up to 20mm that underwent MRI prior to
      tissue diagnosis were included. Two radiologists independently evaluated all
      masses for microscopic lipid, hemorrhage, T2-hyperintensity, T2-homogeneity,
      cystic/necrotic areas, hypervascularity, enhancement homogeneity, circumscribed
      margins, and predominantly exophytic location. These MRI features, as well as
      patient age, gender, and history of RCC, were compared with pathologic findings
      using Fisher's exact test, unpaired t-test, and multivariate logistic regression.
      RESULTS: 26.1% (24/92) of masses under 2 cm were benign, only 32.6% (30/92) were
      clear-cell RCC, and only 7.6% (7/92) were high-grade. Among 16 masses measuring
      up to 1cm, only 12.5% (2/16) were clear-cell RCC, and none was high-grade. Within
      the entire cohort, no MRI or clinical feature showed a significant difference
      between benign and malignant lesions (p >= 0.053). However, for both readers,
      clear-cell RCC exhibited a significantly higher frequency of T2-hyperintensity,
      cystic/necrotic areas, and hypervascularity, and a significantly lower frequency
      of hemorrhage, T2-homogeneity, and enhancement homogeneity (p<0.001-0.036).
      Hypervascularity was a significant independent predictor of clear-cell RCC for
      both readers (p=0.002-0.007), as was T2-hyperintensity for reader 2 (p=0.007).
      CONCLUSION: A substantial fraction of small renal masses were benign, and when
      malignant, largely exhibited indolent pathologic characteristics, particularly
      when measuring under 1cm Although small benign and malignant masses could not be
      differentiated on MRI, hypervascularity showed a significant independent
      association with clear-cell RCC in comparison with other lesions.

PMID- 24882785
TI  - Leptomeningeal collateralization in acute ischemic stroke: impact on prominent
      cortical veins in susceptibility-weighted imaging.
AB  - BACKGROUND: The extent of hypoperfusion is an important prognostic factor in
      acute ischemic stroke. Previous studies have postulated that the extent of
      prominent cortical veins (PCV) on susceptibility-weighted imaging (SWI) reflects
      the extent of hypoperfusion. Our aim was to investigate, whether there is an
      association between PCV and the grade of leptomeningeal arterial
      collateralization in acute ischemic stroke. In addition, we analyzed the
      correlation between SWI and perfusion-MRI findings. METHODS: 33 patients with
      acute ischemic stroke due to a thromboembolic M1-segment occlusion underwent MRI
      followed by digital subtraction angiography (DSA) and were subdivided into two
      groups with very good to good and moderate to no leptomeningeal collaterals
      according to the DSA. The extent of PCV on SWI, diffusion restriction (DR) on
      diffusion-weighted imaging (DWI) and prolonged mean transit time (MTT) on
      perfusion-imaging were graded according to the Alberta Stroke Program Early CT
      Score (ASPECTS). The National Institutes of Health Stroke Scale (NIHSS) scores at
      admission and the time between symptom onset and MRI were documented. RESULTS: 20
      patients showed very good to good and 13 patients poor to no collateralization.
      PCV-ASPECTS was significantly higher for cases with good leptomeningeal
      collaterals versus those with poor leptomeningeal collaterals (mean 4.1 versus
      2.69; p=0.039). MTT-ASPECTS was significantly lower than PCV-ASPECTS in all 33
      patients (mean 1.0 versus 3.5; p<0.00). CONCLUSIONS: In our small study the grade
      of leptomeningeal collateralization correlates with the extent of PCV in SWI in
      acute ischemic stroke, due to the deoxyhemoglobin to oxyhemoglobin ratio.
      Consequently, extensive PCV correlate with poor leptomeningeal collateralization
      while less pronounced PCV correlate with good leptomeningeal collateralization.
      Further SWI is a very helpful tool in detecting tissue at risk but cannot replace
      PWI since MTT detects significantly more ill-perfused areas than SWI, especially
      in good collateralized subjects.

PMID- 24882786
TI  - Background parenchymal enhancement in breast MRIs of breast cancer patients:
      impact on tumor size estimation.
AB  - OBJECTIVE: To evaluate whether the degree of background parenchymal enhancement
      affects the accuracy of tumor size estimation based on breast MRI. METHODS: Three
      hundred and twenty-two patients who had known breast cancer and underwent breast
      MRIs were recruited in our study. The total number of breast cancer cases was
      339. All images were assessed retrospectively for the level of background
      parenchymal enhancement based on the BI-RADS criteria. Maximal lesion diameters
      were measured on the MRIs, and tumor types (mass vs. non-mass) were assessed.
      Tumor size differences between the MRI-based estimates and estimates based on
      pathological examinations were analyzed. The relationship between accuracy and
      tumor types and clinicopathologic features were also evaluated. RESULTS: The
      cases included minimal (47.5%), mild (28.9%), moderate (12.4%) and marked
      background parenchymal enhancement (11.2%). The tumors of patients with minimal
      or mild background parenchymal enhancement were more accurately estimated than
      those of patients with moderate or marked enhancement (72.1% vs. 56.8%; p=0.003).
      The tumors of women with mass type lesions were significantly more accurately
      estimated than those of the women with non-mass type lesions (81.6% vs. 28.6%;
      p<0.001). The tumor of women negative for HER2 was more accurately estimated than
      those of women positive for HER2 (72.2% vs. 51.6%; p=0.047). CONCLUSION: Moderate
      and marked background parenchymal enhancement is related to the inaccurate
      estimation of tumor size based on MRI. Non-mass type breast cancer and HER2
      positive breast cancer are other factors that may cause inaccurate assessment of
      tumor size.

PMID- 24882787
TI  - The anterior tilt angle of the proximal tibia epiphyseal plate: a significant
      radiological finding in young children with trampoline fractures.
AB  - OBJECTIVE: Evaluation of the anterior tilt angle of the proximal tibia epiphyseal
      plate in young children, which suffered a trampoline fracture in comparison with
      a normal population. MATERIALS AND METHODS: 62 children (31 females, 31 males)
      between 2 and 5 years of age (average 2 years 11 months, standard deviation 11
      months) with radiographs in two views of the tibia were included in this
      retrospective study. 25 children with proximal tibia fractures were injured with
      a history of jumping on a trampoline. All other causes for tibia fractures were
      excluded. A normal age-mapped control cohort of 37 children was compared. These
      children had neither evidence of a trampoline related injury nor a fracture of
      the tibia. The anterior tilt angle of the epiphyseal plate of the tibia was
      defined as an angle between the proximal tibia physis and the distal tibia physis
      on a lateral view. Two radiologists evaluated all radiographs for fractures and
      measured the anterior tilt angle in consensus. An unpaired Student's t-test was
      used for statistical analysis (SPSS). Original reports were reviewed and compared
      with the radiological findings and follow-up radiographs. RESULTS: In the normal
      control group, the average anterior tilt angle measured -3.2 degrees , SD +/- 2.8
      degrees . The children with trampoline fractures showed an anterior tilt of +4.4
      degrees , SD +/- 2.9 degrees . The difference was statistically significant,
      P<0.0001. In 6 patients (24% of all patients with confirmed fractures) the
      original report missed to diagnose the proximal tibial fracture. CONCLUSION:
      Young children between 2 and 5 years of age are at risk for proximal tibia
      fractures while jumping on a trampoline. These fractures may be very subtle and
      difficult to detect on initial radiographs. Measurement of the anterior tilt
      angle of the proximal tibia epiphyseal plate on lateral radiographs is supportive
      for interpreting correctly trampoline fractures.

PMID- 24882788
TI  - Human papillomavirus laryngeal tracheal papillomatosis.

PMID- 24882789
TI  - Autoimmunity: Rationalizing possible pathways from initiation to disease.
AB  - Any physiological system that has as its output an activity that is
      biodestructive and ridding must have a way of distinguishing the host (self) from
      that which is other (nonself). The setting in which autoimmunity can be analyzed
      depends, in part and unavoidably, on the way in which the normal self (S)-nonself
      (NS) discrimination is accomplished. Any discussion of autoimmunity should
      include one's view of this latter. To this end, a pathway for the normal S-NS
      discrimination will be proposed. Then, a mechanism for the determination of
      effector class will be considered as autoimmune disease is consequent to it.
      Experiments challenging both the proposed model of normal behavior, as well as
      that of the extrapolation to autoimmunity, will be cited along with a discussion
      of some of the elements which, if rendered defective, would result in
      autoimmunity. The goal is to see how far this particular abstraction based
      largely on the logic of evolutionary biology can meaningfully guide understanding
      of the disease. 

PMID- 24882790
TI  - Population genetics on islands connected by an arbitrary network: an analytic
      approach.
AB  - We analyse a model consisting of a population of individuals which is subdivided
      into a finite set of demes, each of which has a fixed but differing number of
      individuals. The individuals can reproduce, die and migrate between the demes
      according to an arbitrary migration network. They are haploid, with two alleles
      present in the population; frequency-independent selection is also incorporated,
      where the strength and direction of selection can vary from deme to deme. The
      system is formulated as an individual-based model and the diffusion approximation
      systematically applied to express it as a set of nonlinear coupled stochastic
      differential equations. These can be made amenable to analysis through the
      elimination of fast-time variables. The resulting reduced model is analysed in a
      number of situations, including migration-selection balance leading to a
      polymorphic equilibrium of the two alleles and an illustration of how the
      subdivision of the population can lead to non-trivial behaviour in the case where
      the network is a simple hub. The method we develop is systematic, may be applied
      to any network, and agrees well with the results of simulations in all cases
      studied and across a wide range of parameter values. 

PMID- 24882791
TI  - Optimal foraging strategies: Levy walks balance searching and patch exploitation
      under a very broad range of conditions.
AB  - While evidence for optimal random search patterns, known as Levy walks, in
      empirical movement data is mounting for a growing list of taxa spanning motile
      cells to humans, there is still much debate concerning the theoretical generality
      of Levy walk optimisation. Here, using a new and robust simulation environment,
      we investigate in the most detailed study to date (24*10(6) simulations) the
      foraging and search efficiencies of 2-D Levy walks with a range of exponents,
      target resource distributions and several competing models. We find strong and
      comprehensive support for the predictions of the Levy flight foraging hypothesis
      and in particular for the optimality of inverse square distributions of move step
      lengths across a much broader range of resource densities and distributions than
      previously realised. Further support for the evolutionary advantage of Levy walk
      movement patterns is provided by an investigation into the 'feast and famine'
      effect, with Levy foragers in heterogeneous environments experiencing fewer long
      'famines' than other types of searchers. Therefore overall, optimal Levy foraging
      results in more predictable resources in unpredictable environments. 

PMID- 24882792
TI  - On linear models and parameter identifiability in experimental biological
      systems.
AB  - A key problem in the biological sciences is to be able to reliably estimate model
      parameters from experimental data. This is the well-known problem of parameter
      identifiability. Here, methods are developed for biologists and other modelers to
      design optimal experiments to ensure parameter identifiability at a structural
      level. The main results of the paper are to provide a general methodology for
      extracting parameters of linear models from an experimentally measured scalar
      function - the transfer function - and a framework for the identifiability
      analysis of complex model structures using linked models. Linked models are
      composed by letting the output of one model become the input to another model
      which is then experimentally measured. The linked model framework is shown to be
      applicable to designing experiments to identify the measured sub-model and
      recover the input from the unmeasured sub-model, even in cases that the
      unmeasured sub-model is not identifiable. Applications for a set of common model
      features are demonstrated, and the results combined in an example application to
      a real-world experimental system. These applications emphasize the insight into
      answering "where to measure" and "which experimental scheme" questions provided
      by both the parameter extraction methodology and the linked model framework. The
      aim is to demonstrate the tools' usefulness in guiding experimental design to
      maximize parameter information obtained, based on the model structure.

PMID- 24882793
TI  - Social support as a predictor exhaled nitric oxide in healthy individuals across
      time.
AB  - Psychosocial factors such as social support and depression have long been
      associated with health outcomes. Elevated depressive symptoms are usually
      associated with worse health outcomes, whereas social support has been related to
      improvements in health. Nitric oxide levels are an important marker of both
      cardiovascular health and immune function. Research suggests that exhaled nitric
      oxide is affected by stress, negative affect, and depression; however, the effect
      of social support has not been previously explored. Thus, we sought to examine
      the association of social support, negative affect, and depression with exhaled
      nitric oxide in a group of 35 healthy individuals (10 males and 25 females) with
      a mean age of 20.5years across five weekly assessments. Results showed that
      changes in social support within individuals were positively associated with
      levels of exhaled nitric oxide independent of other psychosocial factors. Further
      exploration of the health implications of this positive relationship between
      airway nitric oxide and social support is necessary. 

PMID- 24882795
TI  - Robotic thyroidectomy.
AB  - Robotic thyroidectomy is ideal for patients with indeterminate, likely benign
      lesions less than 3 cm, and a body mass index less than 35 kg/mg(2). Proper arm
      position and padding are important to facilitate exposure and development of the
      working space from axilla to thyroid bed. The working space is developed using
      headlight and retractors without robotic assistance, establishing exposure of the
      thyroid bed from a 5-cm incision in the axilla. Three robotic instruments and a
      stereoscopic endoscope provide excellent visualization of the associated thyroid
      neurovasculature anatomy. 

PMID- 24882794
TI  - Robotic approaches to the pharynx: tonsil cancer.
AB  - Treatment of squamous cell carcinoma of the oropharynx is challenging because of
      its effects on speech and swallowing, which may affect quality of life. Transoral
      robotic surgery may be an effective alternative to open surgery. Robotic lateral
      oropharyngectomy is best suited for early stage oropharyngeal squamous cell
      carcinoma, with the goal of avoiding or reducing the use or dose of adjuvant
      therapies. Successful robotic lateral oropharyngectomy requires appropriate
      training, detailed preoperative planning, organized operating room setup to
      obtain exposure, an understanding of the pertinent surgical anatomy, and
      knowledge of the postoperative care of the oncologic patient. 

PMID- 24882796
TI  - Transoral robotic surgery for larynx cancer.
AB  - Transoral robotic surgery (TORS) has become increasingly used to manage laryngeal
      and pharyngeal cancers, although the published experience in the larynx is small.
      Although there is burgeoning use of TORS for primary pharyngeal cancer, its
      application in the larynx is currently more limited. Successful TORS of the
      larynx has been predominantly as supraglottic laryngectomy, although there is
      some experience in total laryngectomy and cordectomy. Limitations of TORS of the
      larynx are primarily those of access and instrumentation, with respect to both
      the surgical robot and the retractors used to access the larynx transorally. 

PMID- 24882797
TI  - Transoral robotic sleep surgery: the obstructive sleep apnea-hypopnea syndrome.
AB  - Nocturnal upper airway collapse is often multi-level in nature but typically will
      involve some degree of obstruction at the level of the tongue-base. Several
      surgical procedures have been developed in recent years to address this area in
      patients resistant to continuous positive airway pressure. This article outlines
      a novel way to treat obstructive sleep apnea lingual obstruction using the da
      Vinci robotic surgical system. This technique offers significant potential
      advantages over other established approaches and it should be included in the
      surgical armamentarium of sleep surgeons.

PMID- 24882798
TI  - Transoral robotic surgery (TORS) for benign pharyngeal lesions.
AB  - Transoral robotic surgery (TORS) offers a minimally invasive approach to the
      pharynx with a magnified 3-dimensional view, wristed instruments with 7 degrees
      of freedom, and tremor filtration. TORS affords an excellent approach to benign
      lesions of the pharynx. This article is grouped into subsites of the nasopharynx,
      oropharynx, and hypopharynx, addressing patient setup, surgical technique, and
      postoperative management of each subsite. Although TORS has been described
      primarily for resection of malignant lesions of the pharynx, the setup, exposure,
      and anatomy described herein are identical for benign lesions, the difference
      being the magnitude of resection. 

PMID- 24882799
TI  - Robotic surgery of the skull base.
AB  - Minimally invasive skull base surgery has advanced substantially with the advent
      of endoscopic technology, novel instrumentation, and intraoperative image
      guidance capabilities. Robotic technology has been accepted into the surgeon's
      armamentarium, with its implementation into abdominal, thoracic, and head and
      neck surgery. However, the application of surgical robotics to the skull base has
      yet to be achieved. This article highlights current preclinical research and
      applications of robotic surgery to the skull base. 

PMID- 24882800
TI  - Robotic facelift thyroidectomy.
AB  - The use of minimally invasive and endoscopic thyroidectomy techniques has become
      widespread. However, these procedures all result in a visible neck incision.
      Several remote access thyroidectomy approaches that place the necessary incision
      in inconspicuous, noncervical locations have recently been described. Robotic
      facelift thyroidectomy uses a facelift incision in the postauricular area to
      provide entry to the thyroid compartment. Robotic facelift thyroidectomy has been
      shown to be feasible and safe and an increasing number of institutions have begun
      to offer it to selected patients. This article describes the indications,
      technical details, outcomes, and potential complications of this procedure. 

PMID- 24882801
TI  - Robotic approaches to the neck.
AB  - This article introduces and evaluates the feasibility of robot-assisted neck
      dissection as well as robot-assisted neck surgery via a modified facelift or
      retroauricular approach. Robot-assisted neck surgery is feasible compared with
      conventional techniques and shows a clear cosmetic benefit. 

PMID- 24882802
TI  - Robotic surgery of the head and neck.

PMID- 24882803
TI  - Monitoring the kinetics of CellTraceTM calcein red-orange AM intracellular
      accumulation with spatial intensity distribution analysis.
AB  - BACKGROUND: Routine black box approaches quantify fluorescence intensity to
      profile the uptake of fluorophores, providing limited insight into microscopic
      events. Spatial intensity distribution analysis has previously been reported to
      quantify oligomerisation and number of particles from selected regions and
      profile intracellular distributions of labelled moieties. METHODS: In this study,
      the concentration and time-dependent behaviour of CellTraceTM calcein red-orange
      (AM) intracellular accumulation was examined in colorectal adenocarcinoma cell
      line and bovine aortic endothelial cells. Monolayers were subjected to
      fluorescence correlation spectroscopy, fluorescence intensity and SpIDA
      measurements to determine differences in the rate and extent of intracellular
      accumulation. RESULTS: Intracellular accumulation data derived from Spatial
      intensity distribution analysis were found to correlate with that of fluorescence
      correlation spectroscopy and fluorescence intensity profiles. The extent of
      intracellular accumulation was found to be time and concentration-dependent in
      both cell lines examined, with no significant differences in the rate of
      intracellular accumulation. CONCLUSIONS: Spatial intensity distribution analysis
      applied at 'proof of concept' level is a rapid and user-friendly tool that can be
      applied to the quantification of intracellular concentration and kinetics of
      fluorophore uptake. GENERAL SIGNIFICANCE: Confocal imaging as a routinely
      implemented tool for profiling fluorescently-labelled species is often under
      exploited for yielding quantitative parameters.

PMID- 24882804
TI  - IL-32gamma induces chemotaxis of activated T cells via dendritic cell-derived
      CCL5.
AB  - Interleukin (IL)-32 has been associated with a variety of inflammatory diseases
      including rheumatoid arthritis, vasculitis and Crohn's disease. We have
      previously reported that IL-32gamma, the IL-32 isoform with the highest
      biological activity, could act as an immune modulator through regulation of
      dendritic cell (DC) functions in immune responses. Cell locomotion is crucial for
      induction of an effective immune response. In this study, we investigated the
      effect and underlying mechanisms of IL-32gamma on recruitment of T cells. IL
      32gamma upregulated the expression of several chemokines including CCL2, CCL4,
      and CCL5 in the DCs. In particular, IL-32gamma significantly increased CCL5
      expression in a dose-dependent manner. Treatment with JNK and NF-kappaB
      inhibitors suppressed IL-32gamma-induced CCL5 expression in DCs, indicating that
      IL-32gamma induced CCL5 production through the JNK and NF-kappaB pathways.
      Furthermore, supernatants from IL-32gamma-treated DCs showed chemotactic
      activities controlling migration of activated CD4(+) and CD8(+) T cells, and
      these activities were suppressed by addition of neutralizing anti-CCL5 antibody.
      These results show that IL-32gamma effectively promotes migration of activated T
      cells via CCL5 production in DCs. The chemotactic potential of IL-32gamma may
      explain the pro-inflammatory effects of IL-32 and the pathologic role of IL-32 in
      immune disorders such as rheumatoid arthritis. 

PMID- 24882807
TI  - Access and benefit sharing of Antarctica's biological material.
AB  - Searching and sampling of Antarctic Biological Material (ABM) is happening with
      no explicit regulation on access and benefit sharing requirements. Patents
      already exist on inventions stemming from Antarctic living organisms. The
      Antarctic Treaty System (ATS) provides mechanisms to ensure that scientific
      knowledge and data generated from the collection and use of ABM are shared,
      although commercialization might be a threat to this free exchange of scientific
      knowledge. Some of the underlying problems regarding the access and benefit
      sharing of ABM are that under the ATS there are gaps concerning definitions,
      access to specimens, benefit sharing, commercialization and reporting issues. The
      Antarctic Treaty Consultative Parties (ATCPs) have decided that the Antarctic
      Treaty Consultative Meeting (ATCM) is the competent body to discuss the matter,
      and the ATS is the appropriate framework for managing the collection of
      biological material in the Antarctic Treaty area and for considering its use.
      Nevertheless, opinions diverge as to the need for more specific rules on access
      and benefit sharing other than that already resulting from the obligation to give
      prior notification and share scientific results. 

PMID- 24882805
TI  - Subunit architecture and functional modular rearrangements of the transcriptional
      mediator complex.
AB  - The multisubunit Mediator, comprising ~30 distinct proteins, plays an essential
      role in gene expression regulation by acting as a bridge between DNA-binding
      transcription factors and the RNA polymerase II (RNAPII) transcription machinery.
      Efforts to uncover the Mediator mechanism have been hindered by a poor
      understanding of its structure, subunit organization, and conformational
      rearrangements. By overcoming biochemical and image analysis hurdles, we obtained
      accurate EM structures of yeast and human Mediators. Subunit localization
      experiments, docking of partial X-ray structures, and biochemical analyses
      resulted in comprehensive mapping of yeast Mediator subunits and a complete
      reinterpretation of our previous Mediator organization model. Large-scale
      Mediator rearrangements depend on changes at the interfaces between previously
      described Mediator modules, which appear to be facilitated by factors conducive
      to transcription initiation. Conservation across eukaryotes of Mediator
      structure, subunit organization, and RNA polymerase II interaction suggest
      conservation of fundamental aspects of the Mediator mechanism. 

PMID- 24882809
TI  - The concept of function in modern physiology.
AB  - An overview of the scientific literature shows that the concept of function is
      central in physiology. However, the concept itself is not defined by
      physiologists. On the other hand, the teleological, namely, the 'goal-directed'
      dimension of function, and its subsequent explanatory relevance, is a
      philosophical problem. Intuitively, the function of a trait in a system explains
      why this trait is present, but, in the early 1960s, Ernest Nagel and Carl Hempel
      have shown that this inference cannot be logically founded. However, they showed
      that self-regulated systems are teleological. According to the selectionist
      theories, the function of an item is its effect that has been selected by natural
      selection, a process that explains its presence. As they restrict the functional
      attribution of a trait to its past selective value and not its current
      properties, these theories are inconsistent with the concept of function in
      physiology. A more adequate one is the causal role theory, for which a function
      of a trait in a system is its causal contribution to the functional capacity of
      the system. However, this leaves unsolved the question of the 'surplus meaning'
      of the teleological dimension of function. The significance of considering
      organisms as 'purpose-like' (teleological) systems may reside not in its
      explanatory power but in its methodological fruitfulness in physiology. In this
      view, the teleological dimension of physiological functions is convergent to but
      not imported from, the teleological dimension of evolutionary biology. 

PMID- 24882808
TI  - Evolution evolves: physiology returns to centre stage.

PMID- 24882811
TI  - The evolutionary origin of form and function.
AB  - We regard the basic unit of the organism, the cell, as a complex dissipative
      natural process functioning under the second law of thermodynamics and the
      principle of least action. Organisms are conglomerates of information bearing
      cells that optimise the efficiency of energy (nutrient) extraction from its
      ecosystem. Dissipative processes, such as peptide folding and protein
      interaction, yield phenotypic information from which form and function emerge
      from cell to cell interactions within the organism. Organisms, in Darwin's
      'proportional numbers', in turn interact to minimise the free energy of their
      ecosystems. Genetic variation plays no role in this holistic conceptualisation of
      the life process. 

PMID- 24882810
TI  - Epigenetic resolution of the 'curse of complexity' in adaptive evolution of
      complex traits.
AB  - The age of most genes exceeds the longevity of their genomic and physiological
      associations by many orders of magnitude. Such transient contexts modulate the
      expression of ancient genes to produce currently appropriate and often highly
      distinct developmental and functional outcomes. The efficacy of such adaptive
      modulation is diminished by the high dimensionality of complex organisms and
      associated vast areas of neutrality in their genotypic and developmental networks
      (and, thus, weak natural selection). Here I explore whether epigenetic effects
      facilitate adaptive modulation of complex phenotypes by effectively reducing the
      dimensionality of their deterministic networks and thus delineating their
      developmental and evolutionary trajectories even under weak selection. Epigenetic
      effects that link unconnected or widely dispersed elements of genotype space in
      ecologically relevant time could account for the rapid appearance of functionally
      integrated adaptive modifications. On an organismal time scale, conceptually
      similar processes occur during recurrent epigenetic reprogramming of somatic stem
      cells to produce, recurrently and reversibly, a bewildering array of
      differentiated and persistent cell lineages, all sharing identical genomic
      sequences despite strongly distinct phenotypes. I discuss whether close
      dependency of onset, scope and duration of epigenetic effects on cellular and
      genomic context in stem cells could provide insights into contingent modulation
      of conserved genomic material on a much longer evolutionary time scale. I review
      potential empirical examples of epigenetic bridges that reduce phenotype
      dimensionality and accomplish rapid adaptive modulation in the evolution of
      novelties, expression of behavioural types, and stress-induced ossification
      schedules. 

PMID- 24882812
TI  - Bioattractors: dynamical systems theory and the evolution of regulatory
      processes.
AB  - In this paper, we illustrate how dynamical systems theory can provide a unifying
      conceptual framework for evolution of biological regulatory systems. Our argument
      is that the genotype-phenotype map can be characterized by the phase portrait of
      the underlying regulatory process. The features of this portrait--such as
      attractors with associated basins and their bifurcations--define the regulatory
      and evolutionary potential of a system. We show how the geometric analysis of
      phase space connects Waddington's epigenetic landscape to recent computational
      approaches for the study of robustness and evolvability in network evolution. We
      discuss how the geometry of phase space determines the probability of possible
      phenotypic transitions. Finally, we demonstrate how the active, self-organizing
      role of the environment in phenotypic evolution can be understood in terms of
      dynamical systems concepts. This approach yields mechanistic explanations that go
      beyond insights based on the simulation of evolving regulatory networks alone.
      Its predictions can now be tested by studying specific, experimentally tractable
      regulatory systems using the tools of modern systems biology. A systematic
      exploration of such systems will enable us to understand better the nature and
      origin of the phenotypic variability, which provides the substrate for evolution
      by natural selection.

PMID- 24882813
TI  - The genome as a developmental organ.
AB  - This paper applies the conceptual toolkit of Evolutionary Developmental Biology
      (evo-devo) to the evolution of the genome and the role of the genome in organism
      development. This challenges both the Modern Evolutionary Synthesis, the dominant
      view in evolutionary theory for much of the 20th century, and the typically
      unreflective analysis of heredity by evo-devo. First, the history of the
      marginalization of applying system-thinking to the genome is described. Next, the
      suggested framework is presented. Finally, its application to the evolution of
      genome modularity, the evolution of induced mutations, the junk DNA versus ENCODE
      debate, the role of drift in genome evolution, and the relationship between
      genome dynamics and symbiosis with microorganisms are briefly discussed. 

PMID- 24882814
TI  - Endogenous bioelectrical networks store non-genetic patterning information during
      development and regeneration.
AB  - Pattern formation, as occurs during embryogenesis or regeneration, is the crucial
      link between genotype and the functions upon which selection operates. Even
      cancer and aging can be seen as challenges to the continuous physiological
      processes that orchestrate individual cell activities toward the anatomical needs
      of an organism. Thus, the origin and maintenance of complex biological shape is a
      fundamental question for cell, developmental, and evolutionary biology, as well
      as for biomedicine. It has long been recognized that slow bioelectrical gradients
      can control cell behaviors and morphogenesis. Here, I review recent molecular
      data that implicate endogenous spatio-temporal patterns of resting potentials
      among non-excitable cells as instructive cues in embryogenesis, regeneration, and
      cancer. Functional data have implicated gradients of resting potential in
      processes such as limb regeneration, eye induction, craniofacial patterning, and
      head-tail polarity, as well as in metastatic transformation and tumorigenesis.
      The genome is tightly linked to bioelectric signaling, via ion channel proteins
      that shape the gradients, downstream genes whose transcription is regulated by
      voltage, and transduction machinery that converts changes in bioelectric state to
      second-messenger cascades. However, the data clearly indicate that bioelectric
      signaling is an autonomous layer of control not reducible to a biochemical or
      genetic account of cell state. The real-time dynamics of bioelectric
      communication among cells are not fully captured by transcriptomic or proteomic
      analyses, and the necessary-and-sufficient triggers for specific changes in
      growth and form can be physiological states, while the underlying gene loci are
      free to diverge. The next steps in this exciting new field include the
      development of novel conceptual tools for understanding the anatomical semantics
      encoded in non-neural bioelectrical networks, and of improved biophysical tools
      for reading and writing electrical state information into somatic tissues.
      Cracking the bioelectric code will have transformative implications for
      developmental biology, regenerative medicine, and synthetic bioengineering. 

PMID- 24882815
TI  - Inheritance is where physiology meets evolution.
AB  - Physiology and evolutionary biology have developed as two separated disciplines,
      a separation that mirrored the hypothesis that the physiological and evolutionary
      processes could be decoupled. We argue that non-genetic inheritance shatters the
      frontier between physiology and evolution, and leads to the coupling of
      physiological and evolutionary processes to a point where there exists a
      continuum between accommodation by phenotypic plasticity and adaptation by
      natural selection. This approach is also profoundly affecting the definition of
      the concept of phenotypic plasticity, which should now be envisaged as a multi
      scale concept. We further suggest that inclusive inheritance provides a
      quantitative way to help bridging infra-individual (i.e. physiology) with supra
      individual (i.e. evolution) approaches, in a way that should help building the
      long sough inclusive evolutionary synthesis.

PMID- 24882818
TI  - Non-coding RNAs as the bridge between epigenetic mechanisms, lineages and domains
      of life.
AB  - Many cases of heritable environmental responses have been documented but the
      underlying mechanisms are largely unknown. Recently, inherited RNA interference
      has been shown to act as a multigenerational genome surveillance apparatus. We
      suggest that inheritance of regulatory RNAs is at the root of many other
      epigenetic phenomena, the trigger that induces other epigenetic mechanisms, such
      as the depositing of histone modifications and DNA methylation. In addition, we
      explore the possibility that interacting organisms influence each other's
      transcriptomes by exchanging heterologous non-coding RNAs. 

PMID- 24882817
TI  - The biology of developmental plasticity and the Predictive Adaptive Response
      hypothesis.
AB  - Many forms of developmental plasticity have been observed and these are usually
      beneficial to the organism. The Predictive Adaptive Response (PAR) hypothesis
      refers to a form of developmental plasticity in which cues received in early life
      influence the development of a phenotype that is normally adapted to the
      environmental conditions of later life. When the predicted and actual
      environments differ, the mismatch between the individual's phenotype and the
      conditions in which it finds itself can have adverse consequences for Darwinian
      fitness and, later, for health. Numerous examples exist of the long-term effects
      of cues indicating a threatening environment affecting the subsequent phenotype
      of the individual organism. Other examples consist of the long-term effects of
      variations in environment within a normal range, particularly in the individual's
      nutritional environment. In mammals the cues to developing offspring are often
      provided by the mother's plane of nutrition, her body composition or stress
      levels. This hypothetical effect in humans is thought to be important by some
      scientists and controversial by others. In resolving the conflict, distinctions
      should be drawn between PARs induced by normative variations in the developmental
      environment and the ill effects on development of extremes in environment such as
      a very poor or very rich nutritional environment. Tests to distinguish between
      different developmental processes impacting on adult characteristics are
      proposed. Many of the mechanisms underlying developmental plasticity involve
      molecular epigenetic processes, and their elucidation in the context of PARs and
      more widely has implications for the revision of classical evolutionary theory. 

PMID- 24882819
TI  - Cross-species cloning: influence of cytoplasmic factors on development.
AB  - It is widely accepted that the crosstalk between naive nucleus and maternal
      factors deposited in the egg cytoplasm before zygotic genome activation is
      crucial for early development. This crosstalk may also exert some influence on
      later development. It is interesting to clarify the relative roles of the zygotic
      genome and the cytoplasmic factors in development. Cross-species nuclear transfer
      (NT) between two distantly related species provides a unique system to study the
      relative role and crosstalk between egg cytoplasm and zygotic nucleus in
      development. In this review, we will summarize the recent progress of cross
      species NT, with emphasis on the cross-species NT in fish and the influence of
      cytoplasmic factors on development. Finally, we conclude that the developmental
      process and its evolution should be interpreted in a systemic way, rather than in
      a way that solely focuses on the role of the nuclear genome. 

PMID- 24882820
TI  - Chasing Mendel: five questions for personalized medicine.
AB  - Ideas about personalized medicine are underpinned in part by evolutionary
      biology's Modern Synthesis. In this essay we link personalized medicine to the
      efforts of the early statistical investigators who quantified the heritability of
      human phenotype and then attempted to reconcile their observations with Mendelian
      genetics. As information about the heritability of common diseases was obtained,
      similar efforts were directed at understanding the genetic basis of disease
      phenotypes. These ideas were part of the rationale driving the Human Genome
      Project and subsequently the personalized medicine movement. In this context, we
      discuss: (1) the current state of the genotype-phenotype relationship in humans,
      (2) the common-disease-common-variant hypothesis, (3) the current ability of
      'omic' information to inform clinical decision making, (4) emerging ideas about
      the therapeutic insight available from rare genetic variants, and (5) the social
      and behavioural barriers to the wider potential success of personalized medicine.
      There are significant gaps in knowledge as well as conceptual, intellectual, and
      philosophical limitations in each of these five areas. We then provide specific
      recommendations to mitigate these limitations and close by asking if it is time
      for the biomedical research community to 'stop chasing Mendel?' 

PMID- 24882821
TI  - Biophysical constraints on the evolution of tissue structure and function.
AB  - Phylogenetic analyses based on models of molecular sequence evolution have driven
      to industrial scale the generation, cataloguing and modelling of nucleic acid and
      polypeptide structure. The recent application of these techniques to study the
      evolution of protein interaction networks extends this analytical rigour to the
      study of nucleic acid and protein function. Can we further extend phylogenetic
      analysis of protein networks to the study of tissue structure and function? If
      the study of tissue phylogeny is to join up with mainstream efforts in the
      molecular evolution domain, the continuum field description of tissue biophysics
      must be linked to discrete descriptions of molecular biochemistry. In support of
      this goal we discuss tissue units, and biophysical constraints to molecular
      function associated with these units, to present a rationale with which to model
      tissue evolution. Our rationale combines a multiscale hierarchy of functional
      tissue units (FTUs) with the corresponding application of physical laws to
      describe molecular interaction networks and flow processes over continuum fields
      within these units. Non-dimensional numbers, derived from the equations governing
      biophysical processes in FTUs, are proposed as metrics for comparative studies
      across individuals, species or evolutionary time. We also outline the challenges
      inherent to the systematic cataloguing and phylogenetic analysis of tissue
      features relevant to the maintenance and regulation of molecular interaction
      networks. These features are key to understanding the core biophysical
      constraints on tissue evolution. 

PMID- 24882822
TI  - From gene action to reactive genomes.
AB  - Poised at a critical turning point in the history of genetics, recent work (e.g.
      in genomics, epigenetics, genomic plasticity) obliges us to critically reexamine
      many of our most basic concepts. For example, I argue that genomic research
      supports a radical transformation in our understanding of the genome--a shift
      from an earlier conception of that entity as an effectively static collection of
      active genes to that of a dynamic and reactive system dedicated to the context
      specific regulation of protein-coding sequences.

PMID- 24882823
TI  - The holist tradition in twentieth century genetics. Wilhelm Johannsen's genotype
      concept.
AB  - The terms 'genotype', 'phenotype' and 'gene' originally had a different meaning
      from that in the Modern Synthesis. These terms were coined in the first decade of
      the twentieth century by the Danish plant physiologist Wilhelm Johannsen. His
      bean selection experiment and his theoretical analysis of the difference between
      genotype and phenotype were important inputs to the formation of genetics as a
      well-defined special discipline. This paper shows how Johannsen's holistic
      genotype theory provided a platform for criticism of narrowly genocentric
      versions of the chromosome theory of heredity that came to dominate genetics in
      the middle decades of the twentieth century. Johannsen came to recognize the
      epoch-making importance of the work done by the Drosophila group, but he
      continued to insist on the incompleteness of the chromosome theory. Genes of the
      kind that they mapped on the chromosomes could only give a partial explanation of
      biological heredity and evolution. 

PMID- 24882825
TI  - About that health care icon dangling around your neck: do we have some cleaning
      up to do?

PMID- 24882826
TI  - Cardiac diagnostic testing: what bedside nurses need to know.
AB  - Coronary artery disease affects more than 385000 persons annually and continues
      to be a leading cause of death in the United States. Recently, the number of
      available noninvasive cardiac diagnostic tests has increased substantially.
      Nurses should be knowledgeable about available noninvasive cardiac diagnostic
      testing. The common noninvasive cardiac diagnostic testing procedures used to
      diagnose coronary heart disease are transthoracic echocardiography, stress
      testing (exercise, pharmacological, and nuclear), multidetector computed
      tomography, coronary artery calcium scoring (with electron beam computed
      tomography or computed tomographic angiography), and cardiac magnetic resonance
      imaging. Objectives include (1) describing available methods for noninvasive
      assessment of coronary artery disease, (2) identifying which populations each
      test is most appropriate for, (3) discussing advantages and limitations of each
      method of testing, (4) identifying nursing considerations when caring for
      patients undergoing various methods of testing, and (5) describing outcome
      findings of various methods. 

PMID- 24882827
TI  - Neuromonitoring indications and utility in the intensive care unit.
AB  - Information on the use of neuromonitoring in intensive care units is scattered
      but significant. Nurses who do not care for neurologically impaired patients on a
      daily basis may not have a strong understanding of the utility of various
      neuromonitoring techniques, why they are used, or how they are interpreted. Two
      main types of neuromonitoring that are frequently seen but poorly understood are
      reviewed here: transcranial Doppler sonography and electrophysiology. Information
      on these 2 techniques tends to be either superficial with limited applicability
      to the critical care setting or very technical. This review provides information
      about neuromonitoring to help guide critical care nurses providing care to
      neurologically impaired patients.

PMID- 24882816
TI  - Physiology of the read-write genome.
AB  - Discoveries in cytogenetics, molecular biology, and genomics have revealed that
      genome change is an active cell-mediated physiological process. This is
      distinctly at variance with the pre-DNA assumption that genetic changes arise
      accidentally and sporadically. The discovery that DNA changes arise as the result
      of regulated cell biochemistry means that the genome is best modelled as a read
      write (RW) data storage system rather than a read-only memory (ROM). The evidence
      behind this change in thinking and a consideration of some of its implications
      are the subjects of this article. Specific points include the following: cells
      protect themselves from accidental genome change with proofreading and DNA damage
      repair systems; localized point mutations result from the action of specialized
      trans-lesion mutator DNA polymerases; cells can join broken chromosomes and
      generate genome rearrangements by non-homologous end-joining (NHEJ) processes in
      specialized subnuclear repair centres; cells have a broad variety of natural
      genetic engineering (NGE) functions for transporting, diversifying and
      reorganizing DNA sequences in ways that generate many classes of genomic
      novelties; natural genetic engineering functions are regulated and subject to
      activation by a range of challenging life history events; cells can target the
      action of natural genetic engineering functions to particular genome locations by
      a range of well-established molecular interactions, including protein binding
      with regulatory factors and linkage to transcription; and genome changes in
      cancer can usefully be considered as consequences of the loss of homeostatic
      control over natural genetic engineering functions. 

PMID- 24882828
TI  - Designing a critical care nurse-led rapid response team using only available
      resources: 6 years later.
AB  - Rapid response teams have been introduced to intervene in the care of patients
      whose condition deteriorates unexpectedly by bringing clinical experts quickly to
      the patient's bedside. Evidence supporting the need to overcome failure to
      deliver optimal care in hospitals is robust; whether rapid response teams
      demonstrate benefit by improving patient safety and reducing the occurrence of
      adverse events remains controversial. Despite inconsistent evidence regarding the
      effectiveness of rapid response teams, concerns regarding care and costly
      consequences of unaddressed deterioration in patients' condition have prompted
      many hospitals to implement rapid response teams as a patient safety strategy. A
      cost-neutral structure for a rapid response team led by a nurse from the
      intensive care unit was implemented with the goal of reducing cardiopulmonary
      arrests occurring outside the intensive care unit. The results of 6 years'
      experience indicate that a sustainable and effective rapid response team response
      can be put into practice without increasing costs or adding positions and can
      decrease the percentage of cardiopulmonary arrests occurring outside the
      intensive care unit.

PMID- 24882829
TI  - Harlequin syndrome as a complication of epidural anesthesia.
AB  - Harlequin syndrome is a rare neurological condition that results in unilateral
      facial flushing and sweating. Although the syndrome is generally a benign
      condition with complete resolution if appropriate treatment is initiated,
      unilateral facial flushing can be a sign of several serious conditions and should
      be thoroughly investigated. Sudden onset of facial flushing related to harlequin
      syndrome developed in a patient who had bilateral lung transplant with
      postoperative epidural anesthesia for pain control. Differential diagnosis
      includes neurovascular disease (acute stroke), malignant neoplasm of brain or
      lung, Horner syndrome, idiopathic hyperhidrosis, and Frey syndrome. Harlequin
      syndrome is often easily treated by discontinuing the anesthetic or adjusting
      placement of the epidural catheter.

PMID- 24882830
TI  - Smartphone applications: potential tools for use in preparing for CCRN
      certification examinations.
AB  - Recent advances in smartphone technology now allow clinicians to use commercially
      produced applications when studying for nursing certification examinations. The
      quality of currently available CCRN review applications varies in this first
      generation of products. Most are limited to multiple-choice practice questions,
      although a few have additional elements such as study guides and reference
      charts. Weaknesses found in the applications evaluated include poorly written and
      edited content, questions limited to rote memorization rather than application
      and analysis of knowledge, and content too basic or outside the scope of
      experienced critical care nursing practice. A list of important factors for
      consumers to consider before purchase is provided. 

PMID- 24882831
TI  - Philosophy, baseball, and certification.

PMID- 24882832
TI  - Use of gastric decompression tubes with small-bowel feeding tubes.

PMID- 24882833
TI  - A blue shell.

PMID- 24882835
TI  - I am a critical care nurse.

PMID- 24882836
TI  - A population-based study showing better renal prognosis for proteinase 3
      antineutrophil cytoplasmic antibody (ANCA)-associated nephritis versus
      myeloperoxidase ANCA-associated nephritis.
AB  - OBJECTIVE: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV)
      is usually differentiated based on clinical phenotypes, but recent data indicate
      that myeloperoxidase (MPO)-AAV is genetically distinct from proteinase 3 (PR3)
      AAV. We reviewed a population-based cohort of AAV, focusing on differences in
      clinical and laboratory characteristics and to compare renal outcome between MPO
      ANCA and PR3-ANCA nephritis. METHODS: All new cases of AAV diagnosed between 1997
      and 2009 in a geographically defined area in southern Sweden were retrieved using
      a validated search algorithm. Data were collected from time of diagnosis and end
      of followup. Renal and patient survival were analyzed according to ANCA serotype.
      RESULTS: During the study period, 201 patients were diagnosed with AAV, 98 tested
      positive for PR3-ANCA, and 85 for MPO-ANCA. Patients with PR3-ANCA were younger,
      had significantly higher inflammatory activity, and had a larger number of organs
      involved at diagnosis, but nephritis was more prevalent among patients with MPO
      associated (72/85; 85%) versus PR3-associated disease (67/98, 68%). When
      comparing only patients with ANCA-associated nephritis, those with MPO-ANCA were
      more likely to develop endstage renal disease (n = 27, 38%) than those with PR3
      ANCA (n = 10, 15%), p = 0.003. The risk remained significantly elevated after
      adjusting for sex, age, and s-creatinine level at diagnosis (HR 2.64; 95% CI 1.25
      5.58; p = 0.003). There were no significant differences in mortality rates
      between the 2 groups. CONCLUSION: The outcome in this population-based cohort
      indicates that among AAV patients with nephritis, renal prognosis is better in
      the PR3-ANCA group, even after adjustment for sex, age, and renal function at
      diagnosis.

PMID- 24882837
TI  - A metaanalysis of the increased risk of rheumatoid arthritis-related pulmonary
      disease as a result of serum anticitrullinated protein antibody positivity.
AB  - OBJECTIVE: An inconsistent association has been reported between the serum
      anticitrullinated protein antibodies (ACPA) level and rheumatoid arthritis (RA)
      related pulmonary disease risk. We conducted a metaanalysis to reveal the
      association between them. METHODS: An electronic search was performed in PubMed,
      ScienceDirect, and SpringerLink databases for studies published up to August
      2013. The distributions of the serum ACPA level in cases and controls were
      obtained from eligible studies. The risk of RA-related pulmonary disease
      associated with serum ACPA positivity was estimated by OR and 95% CI. According
      to the heterogeneity results, a fixed-effects model or a random-effects model was
      used to calculate the pooled OR. Publication bias and sensitivity analyses were
      conducted. RESULTS: Overall, 243 patients with RA-related pulmonary disease and
      1442 RA controls were included in the metaanalysis. The results showed that the
      pooled OR was 2.621 (95% CI, 1.561-4.403, p < 0.001) for the increased risk of RA
      related pulmonary disease due to the serum ACPA positivity. In the white
      population subgroup, an increased OR was 3.453 (95% CI 1.798-6.630, p < 0.001),
      whereas no association was found in the Asian population subgroup. Additionally,
      we further revealed that serum ACPA positivity indicated a higher risk for
      interstitial lung disease (ILD) and interstitial pulmonary fibrosis (IPF) among
      patients with RA (OR 4.679, 95% CI 2.071-10.572, p < 0.001). The heterogeneity,
      publication bias, and sensitivity analyses had no statistical significance in any
      group. CONCLUSION: To our knowledge, this is the first metaanalysis to reveal
      that serum ACPA positivity is highly associated with the risk of RA-related
      pulmonary disease, particularly in RA-related ILD and IPF.

PMID- 24882839
TI  - Determinants of arterial stiffness in female patients with Takayasu arteritis.
AB  - OBJECTIVE: The assessment of pulse wave velocity (PWV) in Takayasu arteritis (TA)
      is complex because of many confounding factors. We evaluated PWV in female
      patients with TA and controls with comparable anthropometric and clinical
      variables and assessed a possible association of TA with disease variables.
      METHODS: We evaluated 27 patients with TA consecutively. Exclusion criteria were
      menopause, smoking, diabetes, renal insufficiency, poorly controlled
      hypertension, cardiac arrhythmias, obesity, inflammatory comorbidities,
      pregnancy, and surgical procedures involving the aorta. Disease activity was
      determined by clinical and laboratory variables. As healthy controls, 27 subjects
      with comparable age, blood pressure, height, and weight were selected. Carotid
      femoral PWV measurements were obtained using the Complior system. RESULTS: The
      mean PWV in patients with TA was higher than in healthy controls (9.77 +/- 3.49
      vs 7.83 +/- 1.06 m/s; p = 0.009). Despite our strict selection criteria, patients
      with TA had an average systolic blood pressure (SBP) 8 mmHg higher than controls
      (p = NS), and significantly higher pulse pressure values. The multivariate linear
      regression model shows that 93.8% of the PWV variability is explained by the
      variables age, mean BP, and the disease itself (adjusted R(2) = 0.938). Stepwise
      logistic analysis using the PWV cutoff value established by the receiver-operator
      characteristic curve (> 8.34 m/s) as dependent variable, and measures with
      significance in univariate analysis as independent variables revealed that TA (OR
      4.69; 95% CI 1.31-16.72; p = 0.017) and mean BP (OR 1.06; 95% CI 1.00-1.12; p =
      0.048) were independently associated with higher PWV. Further analysis of disease
      variables revealed that PWV values were not correlated with erythrocyte
      sedimentation rate, C-reactive protein, cumulative dose of glucocorticoid, or
      ejection fraction (p > 0.05). CONCLUSION: In our cohort of female patients with
      TA, the disease itself and mean BP were the strongest determinants associated
      with arterial stiffness.

PMID- 24882838
TI  - Ten-year followup of infliximab therapy in rheumatoid arthritis patients with
      severe, longstanding refractory disease: a cohort study.
AB  - OBJECTIVE: Our study describes the 10-year followup data of the Belgian Expanded
      Access Program (EAP) for infliximab (IFX), which included patients with active
      rheumatoid arthritis who were refractory to methotrexate. The objectives of the
      study were to evaluate the continuation rate, reasons for discontinuation, and
      longterm disease control under IFX treatment, and to study baseline
      characteristics associated with longterm successful IFX therapy. METHODS: Between
      February 2000 and September 2001, 511 patients were enrolled in the Belgian IFX
      EAP, and 507 effectively started IFX therapy. Previously reported data showed
      that 160 patients were still treated with IFX after 7 years of followup. We
      describe the therapy status, reasons for IFX discontinuation, and the level of
      disease activity of this subgroup after 10 years of followup. Baseline
      characteristics of the total EAP cohort were used to describe variables
      associated with longterm successful IFX treatment. RESULTS: After 10 years of
      followup, 110 of the 507 patients (21.7%) were still receiving IFX treatment. In
      the 7-year to 10-year period, which is the focus of the current study, 16
      patients were lost to followup and 34 patients discontinued IFX treatment, mainly
      because of loss of efficacy. Patients successfully treated with IFX for 10 years
      had lower baseline values for 28-joint Disease Activity Score (DAS28), patient
      pain scale, physician visual analog scale, and Health Assessment Questionnaire in
      comparison with the rest of the study cohort. The mean DAS28 level of the
      subgroup still taking IFX after 10 years was 2.55 +/- 1.01. CONCLUSION: In the
      Belgian EAP, 21.7% of patients continued to receive maintenance IFX treatment
      after 10 years of followup. IFX provided good longterm disease control in these
      patients.

PMID- 24882840
TI  - Common variants of cGKII/PRKG2 are not associated with gout susceptibility.
AB  - OBJECTIVE: Recently, genetic analyses indicated the association between gout and
      cGMP-dependent protein kinase 2 (cGKII/PRKG2) gene in a Fukien-Taiwanese heritage
      population. However, no replication study has been reported in other ancestries.
      Therefore, we investigated this association in a Japanese population. METHODS:
      Genotyping of 4 variants (rs11736177, rs10033237, rs7688672, and rs6837293) of
      cGKII was performed in 741 male gout patients and 1302 male controls. RESULTS:
      cGKII variants have no association with gout. CONCLUSION: Our replication study
      suggests that cGKII is not involved in gout susceptibility.

PMID- 24882841
TI  - Telemedicine applied to kinesiotherapy for hand dysfunction in patients with
      systemic sclerosis and rheumatoid arthritis: recovery of movement and
      telemonitoring technology.
AB  - OBJECTIVE: To describe a feasibility study focused on a telemonitoring approach
      to self-managed kinesiotherapy sessions for the rehabilitation of hand function
      in patients with systemic sclerosis (SSc) and rheumatoid arthritis (RA). METHODS:
      Ten patients with SSc and 10 with RA were enrolled in a 3-month controlled trial
      (approval no. 9751/2012 - Italian Department of Health) to perform a home
      kinesiotherapy protocol, consisting of strengthening and mobility exercises,
      using a newly developed telemedicine system (a portable device and the related
      telemonitoring infrastructure). A further 10 patients with SSc and 10 with RA
      were enrolled as controls to perform a similar home kinesiotherapy protocol with
      the aid of common daily-life objects. Both groups were evaluated at baseline and
      at followup, after 6 and 12 weeks. The primary outcome of the trial was hand
      function measured by Dreiser's index (Functional Index for Hand OA, FIHOA),
      Health Assessment Questionnaire (HAQ), and the Hand Mobility in Scleroderma
      (HAMIS) test (only for SSc). RESULTS: Patients with SSc showed an improvement of
      FIHOA in both arms (p < 0.01) but the HAQ (p = 0.016) and the HAMIS test (right
      hand p = 0.016, left hand p = 0.075) improved significantly only in the
      experimental arm. Patients with RA showed a statistically significant improvement
      of FIHOA (p = 0.013) and HAQ (p = 0.015) in the experimental arm, while patients
      in the control arm did not significantly improve. However, no statistically
      significant differences in outcome measures between treatment methods were
      observed. Withdrawals were higher in control arms (SSc 20%; RA 30%) than in
      experimental arms (SSc 10%; RA 10%). CONCLUSION: Telemonitoring of self
      administered kinesiotherapy programs is a promising approach to the
      rehabilitation of hand functions in patients with rheumatic disease.

PMID- 24882842
TI  - The influence of early menopause on cardiovascular risk in women with rheumatoid
      arthritis.
AB  - OBJECTIVE: Early menopause is associated with an increased risk for developing
      rheumatoid arthritis (RA). The risk for cardiovascular disease (CVD) in women
      increases following menopause. Because RA is associated with an increased risk of
      CVD, this study was undertaken to determine whether early menopause affects the
      risk of developing CVD in women with RA. METHODS: A population-based inception
      cohort of 600 women with RA who fulfilled 1987 American College of Rheumatology
      criteria for RA between 1955 and 2007 and were age >= 45 years at diagnosis was
      assembled and followed. Age at menopause and duration of hormone replacement
      therapy, along with occurrence of CVD, was ascertained by review of medical
      records. Cox proportional hazard models compared women who underwent early
      menopause (natural or artificial menopause at age <= 45 yrs) to those within the
      cohort who did not undergo early menopause. RESULTS: Of 600 women, 79 experienced
      early menopause. Women who underwent early menopause were at significantly higher
      risk for developing CVD when compared to women who did not (HR 1.56; 95% CI 1.08
      2.26). CONCLUSION: The risk of CVD in women with RA was higher in those who
      experienced early menopause, and like other known risk factors should increase
      clinician concern for development of CVD in these patients.

PMID- 24882843
TI  - Risk factors for drug-resistant bloodstream infections in patients with systemic
      lupus erythematosus.
AB  - OBJECTIVE: To identify risk factors for developing drug-resistant bacterial
      infections in patients with systemic lupus erythematosus (SLE). METHODS: A
      retrospective, case-control study was performed. Patients fulfilled American
      College of Rheumatology criteria for SLE and had an episode of bloodstream
      infection between 2001 and 2012. Cases were defined as those with bloodstream
      infection caused by drug-resistant bacteria (Pseudomonas aeruginosa, methicillin
      resistant Staphylococcus aureus, or extended-spectrum-beta-lactalamase-producing
      Escherichia coli); while controls had susceptible strains of S. aureus or E.
      coli. Differences between groups were analyzed by Student t test or Mann-Whitney
      U test. Association between variables was assessed by OR (CI 95%). Multivariate
      analysis was performed by binary logistic regression model. RESULTS: Forty-four
      patients were included in each group. Variables associated with drug-resistant
      bloodstream infection were history of central nervous system activity;
      hematological activity, immunosuppressive treatment and prednisone dose at the
      time of the infection; and low C3 levels, antibiotic use, or hospitalization in
      the previous 3 months. In multivariate analysis, variables that remained
      significant were low C3 previous to infection (OR 3.12, CI 95% 1.91-8.22),
      previous hospitalization (OR 2.22, CI 95% 1.42-4.10), and prednisone dose at the
      time of infection (OR 1.10, CI 95% 1.04-1.22). CONCLUSION: Low C3 levels, recent
      hospitalization, and prednisone dose at time of infection are independent risk
      factors for acquiring drug-resistant bacteria in patients with SLE. Although the
      present data do not fully support a change in initial treatment-decision
      strategies, this information could lead to prospective studies designed to
      address this issue, which could determine the best approach in clinical practice.

PMID- 24882846
TI  - Tumor necrosis factor inhibition and adipose tissue distribution -- are reported
      changes relevant to cardiometabolic risk?

PMID- 24882847
TI  - The TREAT study - trial or tribulation?

PMID- 24882848
TI  - Early atlantoaxial subluxation in enthesitis-related arthritis.

PMID- 24882849
TI  - Choroid plexitis as a unique neurological manifestation in granulomatosis with
      polyangiitis (Wegener's disease).

PMID- 24882850
TI  - Prologue: 2013 Annual Meeting of the Group for Research and Assessment of
      Psoriasis and Psoriatic Arthritis (GRAPPA).
AB  - The 2013 Annual Meeting of the Group for Research and Assessment of Psoriasis and
      Psoriatic Arthritis (GRAPPA) was held in July 2013 in Toronto, Canada, and
      attended by rheumatologists, dermatologists, and representatives of
      biopharmaceutical companies and patient groups. We introduce the articles that
      summarize the meeting: A summary of a GRAPPA-organized Fellows Symposium adjacent
      to the 2013 European Academy of Dermatology and Venereology meeting in Istanbul;
      at the GRAPPA meeting proper, proceedings of a trainee symposium, where
      rheumatology fellows and dermatology residents presented their research; a
      summary of experiences and perspectives of psoriasis and psoriatic arthritis
      (PsA) research of 8 patient research partners with PsA who were invited to
      participate as delegates. Other presentations and discussions included an
      interactive session on composite measures of disease severity and response,
      including voting by GRAPPA members; a 3 part update of
      basic/translational/clinical science, including new bone formation, enthesitis
      pathophysiology, and comorbidity monitoring; a 3 part dermatology update on
      psoriasis outcome measures, the Brigham Scalp Nail Inverse Palmoplantar Psoriasis
      Composite Index, and large-scale databases; a short summary of the ongoing GRAPPA
      effort to update treatment guidelines for PsA; updates on several GRAPPA
      educational and rheumatology-related projects; and a discussion of clinical
      criteria to identify inflammatory arthritis, enthesitis, dactylitis, and
      spondylitis as distinguished from non-inflammatory conditions. 

PMID- 24882851
TI  - GRAPPA Fellows Symposium Adjacent to the European Academy of Dermatology and
      Venereology (EADV) Congress, Istanbul, 2013: a meeting report.
AB  - The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis
      (GRAPPA) organized its second Fellows Symposium adjacent to the European Academy
      of Dermatology and Venereology (EADV) congress in Istanbul in October 2013. Wolf
      Henning Boehncke from Geneva, Brian Kirby from Dublin, and Diamant Thaci from
      Lubeck formed the faculty. The 9 best-ranked abstracts submitted to this
      symposium were presented and discussed in detail. Five abstracts focused on
      comorbidities in patients with psoriasis or psoriatic arthritis; summaries of all
      abstracts are included herein. 

PMID- 24882852
TI  - GRAPPA Trainees Symposium 2013: a report from the GRAPPA 2013 Annual Meeting.
AB  - At the 2013 annual meeting of the Group for Research and Assessment of Psoriasis
      and Psoriatic Arthritis (GRAPPA) in Toronto, Ontario, Canada, 26 dermatology and
      rheumatology fellows engaged in psoriasis or psoriatic arthritis research were
      invited to present their work at the Trainees Symposium, which preceded the
      annual meeting and was also attended by GRAPPA members from around the world.
      Herein, we provide a brief overview of the 6 oral presentations and 25 posters
      presented, which reflect the focus and diversity of current basic and clinical
      research in psoriatic disease. 

PMID- 24882854
TI  - Composite disease activity and responder indices for psoriatic arthritis: a
      report from the GRAPPA 2013 meeting on development of cutoffs for both disease
      activity states and response.
AB  - OBJECTIVE: There are several new composite indices for assessing disease activity
      in psoriatic arthritis (PsA). Each may function as a disease state variable and a
      responder index. The aim of our study was to determine cutoffs for disease
      activity and response. METHODS: Data from the Group for GRAPPA Composite Exercise
      (GRACE) study were used to develop cutoffs using a number of different
      approaches. Voting on choice of cutoff was undertaken at the 2013 GRAPPA Annual
      Meeting in Toronto, Ontario, Canada. RESULTS: After voting, results for cutoffs
      for low/high disease activity for the Psoriatic ArthritiS Disease Activity Score
      (PASDAS), GRAppa Composite scorE (GRACE index), and Composite Psoriatic Disease
      Activity Index (CPDAI), respectively, were 3.2/5.4, 2.3/4.7, and 4/8. The
      measurement error for each composite score was estimated at 0.8, 1, and 2 for
      PASDAS, GRACE, and CPDAI, respectively. CONCLUSION: Response criteria for the new
      composite indices have been developed. These now require further validation and
      testing in other datasets.

PMID- 24882855
TI  - Bone formation in psoriatic arthritis: a report from the GRAPPA 2013 Annual
      Meeting.
AB  - The simultaneous presence of bone erosions and bony spurs (osteophytes,
      enthesophytes) in the joints of patients with psoriatic arthritis (PsA) suggests
      that the disease leads to enhanced bone resorption as well as increased bone
      formation, the latter of which has not been observed in patients with rheumatoid
      arthritis. At the 2013 Annual Meeting of the Group for Research and Assessment of
      Psoriasis and Psoriatic Arthritis (GRAPPA), members heard an update on the
      current research into the cytokine signature in PsA and its effects on new bone
      formation. 

PMID- 24882853
TI  - Patient participation in psoriasis and psoriatic arthritis outcome research: a
      report from the GRAPPA 2013 Annual Meeting.
AB  - For the first time, 8 patients with psoriatic arthritis (PsA) participated as
      full delegates at the 2013 Annual Meeting of the Group for Research and
      Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA). Patients were invited
      to provide their perspective for different sessions of the conference program.
      Before the conference, the patient delegates had a separate meeting to
      familiarize themselves with the conference program and to gain a better
      understanding of the vision and objectives of GRAPPA. During the conference, the
      patient group discussed options for increased involvement in research projects.
      Herein we summarize the presentations on patient participation in research, the
      experiences of the patient group, and plans to enhance the patient perspective in
      psoriasis and PsA research. 

PMID- 24882856
TI  - Psoriatic enthesitis: an update from the GRAPPA 2013 Annual Meeting.
AB  - The enthesis, attachment site of ligaments, tendons, and joint capsules to bone,
      has emerged as a complex structure or entheseal organ that dissipates stress to
      maintain homeostasis. Entheses are also anatomically and functionally integrated
      with adjacent bursa, fibrocartilage, and synovium in a synovial entheseal complex
      that may trigger inflammation in response to biomechanical stress. Recent studies
      have suggested that inflammation in psoriatic arthritis (PsA) arises in the
      enthesis based on imaging and anatomical data. In this review, the anatomy of the
      enthesis from a functional perspective is discussed, and the data that support a
      central role for enthesitis in PsA are outlined. In addition, new animal models
      that implicate Th17 and tumor necrosis factor pathways in enthesitis are
      highlighted along with new data that question the primacy of the enthesis in the
      early stages of PsA. Finally, future studies that incorporate new technologies
      are outlined. Those studies may address the contribution of entheseal
      inflammation to initiation and perpetuation of key pathophysiologic pathways in
      the psoriatic joint. 

PMID- 24882857
TI  - GRAPPA 2013 basic/translational/clinical science update: comorbidity monitoring.
AB  - It is now well established that psoriatic disease is associated with increased
      cardiovascular (CV) risk. Screening guidelines and expert recommendations for CV
      risk factors have been published, but these are primarily directed to specific
      specialists (e.g., cardiologists or diabetologists) and may not be well known in
      common practice. The Group for Research and Assessment of Psoriasis and Psoriatic
      Arthritis (GRAPPA) and other organizations are interested in adapting current
      comorbidity screening guidelines for use by dermatologists and rheumatologists.
      The resulting checklists and algorithms will need to be evaluated for
      practicability and performance. 

PMID- 24882858
TI  - The International Dermatology Outcome Measures initiative as applied to psoriatic
      disease outcomes: a report from the GRAPPA 2013 meeting.
AB  - In the United States, access to care is the number one issue facing our patients
      with dermatological conditions. In part, this is because we do not have outcome
      measures that are useful in clinical practice and available in databases where
      payers and governmental agencies can compare the performance of physicians and
      treatments. There is a growing recognition that insufficient attention has been
      paid to the outcomes measured in clinical trials and subsequently in clinical
      practice. The International Dermatology Outcome Measures group includes all
      willing stakeholders: patients, physicians, payers, and pharmaceutical
      scientists. As reported herein, the group's goal is to develop outcome measures
      in dermatology that address the needs of all involved. 

PMID- 24882859
TI  - The Brigham Scalp Nail Inverse Palmoplantar Psoriasis Composite Index (B-SNIPI):
      a novel index to measure all non-plaque psoriasis subsets.
AB  - Psoriasis is a chronic inflammatory disease that encompasses a large spectrum of
      clinically distinct subtypes. Although chronic plaque psoriasis is reported as
      the most common form of psoriatic skin disease, there is growing evidence that
      other variants including scalp, nail, inverse, and palmoplantar psoriasis are
      prevalent, undertreated, and associated with significant impairment in quality of
      life. Currently, the Psoriasis Area and Severity Index (PASI) is the standard to
      assess psoriasis severity as well as response to treatment; however, the PASI has
      several limitations. In response to this need and as a complementary objective
      measure to the PASI, we created the Brigham Scalp Nail Inverse Palmoplantar
      Psoriasis Composite Index (B-SNIPI), based on patient-surveyed, patient-reported
      outcomes equally weighted with physician assessment of disease activity. Herein
      we summarize the B-SNIPI as presented at the 2013 Annual Meeting of the Group for
      Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA). 

PMID- 24882860
TI  - Outcomes research in psoriasis and psoriatic arthritis using large databases and
      research networks: a report from the GRAPPA 2013 Annual Meeting.
AB  - Advances in healthcare informatics have increased the ability to address real
      world, clinically relevant questions using large databases. When examining data
      sources, researchers and clinicians need to consider data validity, potential
      sources of misclassification, whether the source is sufficiently powered to
      detect clinically relevant differences, ability to obtain longitudinal data,
      containment of patients within a database, and ability to obtain structured point
      of-care data. Population-based databases create opportunities for characterizing
      natural history of psoriatic diseases, conducting comparative effectiveness
      research, determining comorbidities, and providing epidemiology-based rational
      approaches to mechanistic investigations. Herein, we discuss the major data
      sources for clinical research in psoriasis, including electronic medical records,
      research networks, disease registries, and others. 

PMID- 24882861
TI  - GRAPPA treatment recommendations: an update from the GRAPPA 2013 Annual Meeting.
AB  - Psoriatic arthritis (PsA) is a chronic systemic inflammatory disorder
      characterized by the association of arthritis and periarticular inflammation in
      patients with psoriasis. In addition to a heterogeneous and variable clinical
      course, PsA is complex and multifaceted and may include prominent involvement in
      the peripheral and axial diarthrodial joints, the skin and nails, and in
      periarticular structures such as entheses. A central mission of the Group for
      Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) is to
      develop guidelines, based upon the best scientific evidence, for the optimal
      treatment of patients with PsA. Guidelines were previously published in 2009
      based on an evidence-based systematic review. Given important recent developments
      and robust ongoing research into the treatment of PsA, GRAPPA undertook to update
      the guidelines. Herein we outline the specific methods and procedures used both
      in the initial and the current evidence-based, systematic reviews of treatments
      for PsA. We also review the numerous discussions regarding how best to finalize
      and publish these new guidelines in 2014. 

PMID- 24882862
TI  - Psoriasis and psoriatic arthritis educational initiatives: an update from the
      2013 GRAPPA Annual Meeting.
AB  - At the 2013 annual meeting of the Group for Research and Assessment of Psoriasis
      and Psoriatic Arthritis (GRAPPA), members were updated on educational areas in
      psoriasis and psoriatic arthritis (PsA). Discussions included (1) the psoriasis
      and PsA GRAPPA video project, comprising a set of educational online videos that
      provide standardized psoriatic disease endpoint training to clinicians and
      researchers; (2) the GRAPPA Educational Outreach Project, focused on cross
      disciplinary education for rheumatologists and dermatologists and including
      several collaborations to expand educational sessions globally; (3) the
      Dermatology and Rheumatology Trainee Educational Initiative, that provides
      psoriatic disease education to medical students, residents, and fellows training
      in dermatology and/or rheumatology; and (4) the GRAPPA Educational Slide Library,
      developed as a resource for GRAPPA members for their own educational
      presentations. 

PMID- 24882863
TI  - GRAPPA 2013 Annual Meeting, rheumatology updates: psoriatic arthritis (PsA)
      biomarker project, arthritis mutilans, PsA-peripheral spondyloarthritis
      epidemiology project.
AB  - At the 2013 annual meeting of the Group for Research and Assessment of Psoriasis
      and Psoriatic Arthritis (GRAPPA), several key GRAPPA projects on musculoskeletal
      aspects of psoriatic disease were reviewed. In this article, lead investigators
      summarize the progress made in a multicenter study, the PsA BioDam (Psoriatic
      Arthritis Biomarkers for Joint Damage), to identify soluble biomarkers for joint
      damage, as well as developing classification criteria for arthritis mutilans.
      Also reviewed are concepts and rationale behind a proposal to study
      classification criteria for peripheral spondyloarthritis, including PsA, reactive
      arthritis, inflammatory bowel disease-associated arthritis, and undifferentiated
      arthritis. 

PMID- 24882864
TI  - Development of criteria to distinguish inflammatory from noninflammatory
      arthritis, enthesitis, dactylitis, and spondylitis: a report from the GRAPPA 2013
      Annual Meeting.
AB  - OBJECTIVE: To describe a research project to develop simple clinical criteria to
      aid in the identification of inflammatory arthritis, enthesitis, dactylitis, and
      spondylitis and distinguish these from non-inflammatory conditions. The criteria
      are particularly intended to aid non-rheumatologists, e.g., dermatologists, who
      need assistance identifying psoriatic arthritis in patients with psoriasis, but
      may be useful to all clinicians in properly diagnosing rheumatologic conditions.
      METHODS: The proposed research methodology includes the use of a nominal group
      exercise among expert clinicians and patient focus groups, Delphi exercises among
      clinicians and patients, application of criteria test sets to a small group of
      representative patients with inflammatory and non-inflammatory musculoskeletal
      conditions, and validation by application of optimal criteria sets to large
      groups of patients with inflammatory and noninflammatory conditions. RESULTS:
      Examples of elements to describe inflammatory conditions derived from a nominal
      group exercise conducted at the 2013 GRAPPA annual meeting are described, along
      with planned project activities. CONCLUSION: This project will lead to the
      development of practical criteria to aid in the diagnosis and appropriate
      clinical care of patients with chronic inflammatory musculoskeletal conditions.

PMID- 24882865
TI  - The art and science of tapering glucocorticoids in patients with rheumatic
      diseases.

PMID- 24882866
TI  - New mutation affecting hypoxanthine phosphoribosyltransferase responsible for
      severe tophaceous gout.

PMID- 24882868
TI  - Roadmap for publishing clinical practice guidelines in PTJ.

PMID- 24882869
TI  - On "Toward a rehabilitation treatment taxonomy: summary of work in progress."
      Dijkers MP, Ferraro MK, Hart T, et al. Phys Ther. 2014;94:319-321.

PMID- 24882870
TI  - Influence of the Phase State of Self-Assembling Redox Mediators on their
      Electrochemical Activity.
AB  - Self-assembling redox mediators have the potential to be broadly useful in a
      range of interfacial electrochemical contexts because the oxidation state and
      state of assembly of the mediator are closely coupled. In this paper, we report
      an investigation of the self-assembly of single- and double-tailed ferrocenyl
      amphiphiles (FTMA and BFDMA, respectively) at the surfaces of Pt electrodes and
      the impact of the dynamic assembled state of the amphiphiles on their rate of
      oxidation. We conclude that frozen aggregates of BFDMA adsorb to the surfaces of
      the Pt electrodes, and that slow dynamics of reorganization BFDMA within these
      aggregates limits the rate of electrooxidation of BFDMA. In contrast, FTMA, while
      forming assemblies on the surfaces of Pt electrodes, is characterized by fast
      reorganization dynamics and a corresponding rate of oxidation that is an order of
      magnitude greater than BFDMA.

PMID- 24882871
TI  - Effect of Flaxseed Meals and Extracts on Lipid Stability in a Stored Meat
      Product.
AB  - Flaxseeds have been recently in focus due to the antioxidant capacity of some of
      their compounds. However, there is a lack of easily accessible information
      concerning their activity against lipid oxidation in food systems. Therefore, the
      aim of the study was to determine the effect of defatted meals (DFM) and the
      aqueous extracts (AFE) obtained from brown and golden flaxseeds on lipid
      oxidation in pork meatballs. Fatty acid composition, peroxide value (PV),
      thiobarbituric acid reactive substances (TBARS) and cholesterol content were
      monitored during 6 months of freezer storage. Cholesterol oxidation products were
      identified and quantified. Both DFM and AFE limited fatty acid and cholesterol
      oxidation during meatball storage. Their antioxidant effect depended on flax
      variety (brown or golden) and preparation type (DFM or AFE). Lower level of PV
      and TBARS, compared with the ones with AFE, were noted in meatballs with DFM.
      Both DFM and AFE, from the brown seed variety, protect the lipids against
      oxidation to a higher extent. During the storage, a cholesterol degradation was
      observed. AFE (particularly from the brown variety) limited changes in
      cholesterol content. Moreover, they stabilized fatty acid composition of stored
      meatballs. However, DFM efficiently inhibited cholesterol oxidation.

PMID- 24882873
TI  - Comments on the Publication of Munich Nomenclature III by the Cytology
      Coordination Conference.

PMID- 24882872
TI  - Isoflavone Content of Soybean Cultivars from Maturity Group 0 to VI Grown in
      Northern and Southern China.
AB  - Soybean isoflavone content has long been considered to be a desirable trait to
      target in selection programs for their contribution to human health and plant
      defense systems. The objective of this study was to determine isoflavone
      concentrations of various soybean cultivars from maturity groups 0 to VI grown in
      various environments and to analyze their relationship to other important seed
      characters. Forty soybean cultivars were grown in replicated trials at Wuhan and
      Beijing of China in 2009/2010 and their individual and total isoflavone
      concentrations were determined by HPLC. Their yield and quality traits were also
      concurrently analyzed. The isoflavone components had abundant genetic variation
      in soybean seed, with a range of coefficient variation from 45.01% to 69.61%.
      Moreover, individual and total isoflavone concentrations were significantly
      affected by cultivar, maturity group, site and year. Total isoflavone
      concentration ranged from 551.15 to 7584.07 MUg g-1, and averaged 2972.64 MUg g-1
      across environments and cultivars. There was a similar trend regarding the
      isoflavone contents, in which a lower isoflavone concentration was generally
      presented in early rather than late maturing soybean cultivars. In spite of
      significant cultivar * year * site interactions, cultivars with consistently high
      or low isoflavone concentrations across environments were identified, indicating
      that a genetic factor plays the most important role for isoflavone accumulation.
      The total isoflavone concentration had significant positive correlations with
      plant height, effective branches, pods per plant, seeds per plant, linoleic acid
      and linolenic acid, while significant negative correlations with oleic acid and
      oil content, indicating that isoflavone concentration can be predicted as being
      associated with other desirable seed characteristics.

PMID- 24882874
TI  - Comment on the "Recommendations for the Diagnosis and Treatment of Endometrial
      Cancer-Update 2013" by G. Emons and P. Mallmann for the Uterus Commission of AGO.

PMID- 24882875
TI  - DGGG Guidelines Programme: Status Quo - Quo Vadis!
AB  - The Guidelines programme of the German Society of Gynaecology and Obstetrics
      (DGGG) is an executive part of the DGGG Guidelines Commission. It includes in
      house planning and organisation of all guidelines as well as representation
      outside of the DGGG. This article does not concern the development of the
      guidelines as much as it concerns the planning, organisation, registration,
      editing and publication of the guidelines in context of the DGGG Guidelines
      programme. It targets interested parties, especially authors and coordinators of
      guidelines.

PMID- 24882876
TI  - Operative and Conservative Treatment of Uterine Sarcomas.
AB  - Uterine sarcomas are rare, aggressive mesenchymal tumours with a relatively poor
      prognosis. The term comprises various histological subtypes, such as
      leiomyosarcoma, endometrial stromal sarcomas as well as undifferentiated uterine
      sarcomas, which require different operative and systemic/radiation therapy
      strategies accordingly. The evidence on operative, adjuvant and palliative
      treatment currently available is presented here.

PMID- 24882877
TI  - Therapy for Primary Vulvar Carcinoma.
AB  - The rather rare vulvar cancer is almost always a squamous cell carcinoma that
      mostly develops from an underlying VIN or HPV infection. In addition, lichen
      sclerosus et atrophicans, immune deficiency, nicotine abuse or anogenital
      intraepithelial neoplasias may play a role in the pathogenesis. Surgical therapy
      aims at an R0 resection in the sense of a complete vulvectomy or a radical local
      excision with, if necessary, plastic reconstruction. Also, the vulvar field
      resection with consideration of the compartment model has been discussed. Besides
      the classic inguinofemoral lymphadenectomy, in selected cases of vulvar cancer
      sentinel biopsies are performed by experienced surgeons in the larger centres. In
      contrast, systemic therapy plays only a subordinate role; in isolated cases down
      staging by means of neoadjuvant chemotherapy may be useful. However, there is at
      present no indication for adjuvant chemotherapy. Neoadjuvant radiochemotherapy is
      also not to be recommended on account of its unfavourable ratio of efficacy to
      side effects. On the other hand adjuvant radiotherapy is indicated in cases of
      positive inguinal lymph nodes. According to the current data the indication
      should be made generously in such cases.

PMID- 24882878
TI  - Disease Management Project Breast Cancer in Hesse - 5-Year Survival Data:
      Successful Model of Intersectoral Communication for Quality Assurance.
AB  - Introduction: The Disease Management Project Breast Cancer (DMP Breast Cancer)
      was first launched in Hesse in 2004. The project is supported by the health
      insurance companies in Hesse and the Professional Association of Gynaecologists
      in Hesse. The aim is to offer structured treatment programmes to all women
      diagnosed with breast cancer in Hesse by creating intersectoral cooperations
      between coordinating clinics, associated hospitals and gynaecologists in private
      practice who registered in the DMP programme. Method: Between 1 January 2005 and
      30 June 2011, 13 973 women were enrolled in the DMP programme. Results: After
      data cleansing, survival rates were calculated for a total of 11 214 women. The 5
      year overall survival (OS) rate was 86.3 %; survival rates according to tumour
      stage on presentation were 92.2 % (pT1) and 82.3 % (pT2), respectively. The
      impact of steroid hormone receptor status on survival (87.8 % for receptor
      positive cancers vs. 78.9 % for receptor-negative cancers) and of age at first
      diagnosis on survival (<= 35 years = 91 %) were calculated. Conclusion: The
      project showed that intersectoral cooperation led to significant improvements in
      the quality of treatment over time, as measured by quality indicators and
      outcomes after treatment.

PMID- 24882879
TI  - Cervical Carcinoma in Early Pregnancy - Successful Birth by Caesarean Section
      Followed by Radical Hysterectomy.
AB  - A cervical carcinoma was diagnosed in a 32-year-old patient in the 17th week of
      her pregnancy. The histological confirmation revealed a well-differentiated
      squamous cell carcinoma. It was a clinical stage Ib1 tumour, without enlarged
      lymph nodes according to the image. After a staging MRI, intensive education of
      the patient and case discussion at the interdisciplinary tumour board as well as
      consultation with the neonatologist, it was agreed to prolong the pregnancy under
      close monitoring. The carcinoma was confined to the cervix in the further course
      of the pregnancy. The elective delivery was planned after 32 weeks of gestation.
      The primary Caesarean section followed by radical hysterectomy Piver II were
      carried out without complications. After regular postoperative progression of the
      mother, brachytherapy was performed at the appropriate time. The premature
      newborn was under neonatal care and exhibited good postnatal adaptation. Mother
      and child were discharged in good health.

PMID- 24882880
TI  - Pulmonary Metastases of a Uterine Smooth Muscle Tumour with Undefined Malignancy
      Potential.
AB  - Smooth muscle neoplasms with atypical proliferative behaviour, but without clear
      histopathological malignancy represent a diagnostic and therapeutic challenge, as
      distinction from a sarcoma can be difficult and no guaranteed treatment
      recommendations are available due to the rarity of these changes. In the event of
      uncertain primary histology, even metastases cannot be assessed as malignancy
      criteria, but may contribute to the clarification of the histology. Similarities
      with other smooth muscle proliferations, such as lymphangioleiomyomatosis, are
      striking. The diagnostic difficulties and treatment options are explained based
      on the example of a 59-year-old patient, in whom a retroperitoneal mass and
      pulmonary lesion of such a tumour occurred 4 years after a hysterectomy. Even
      though the genesis and histological diagnostics have not been conclusively
      clarified, slow growth and a low recurrence rate for post-menopausal patients
      allow for a wait-and-see approach, whereby the option for anti-hormonal treatment
      exists in the event of positive evidence of hormone receptors.

PMID- 24882881
TI  - Teaching High School Chemistry in the Context of Pharmacology Helps Both Teachers
      and Students Learn.
AB  - Few studies demonstrate the impact of teaching chemistry embedded in a context
      that has relevance to high school students. We build upon our prior work showing
      that pharmacology topics (i.e., drugs), which are inherently interesting to high
      school students, provide a useful context for teaching chemistry and biology. In
      those studies, teachers were provided professional development for the
      Pharmacology Education Partnership (PEP) in an onsite venue (either five-day or
      one-day workshop). Given financial difficulties to travel, teachers have asked
      for alternatives for professional development. Thus, we developed the same PEP
      training workshop using a distance learning (DL) (two-way live video) approach.
      In this way, 121 chemistry and biology teachers participated in the DL workshops
      to learn how to incorporate the PEP modules into their teaching. They field
      tested the modules over the year in high school chemistry and biology classes.
      Teacher knowledge of chemistry and biology increased significantly after the
      workshop and was maintained for at least a year. Their students (N = 2309)
      demonstrated a significant increase in knowledge of chemistry and biology
      concepts, with higher scores as the number of modules used increased. The
      increase in both teacher and student knowledge in these subjects was similar to
      that found previously when teachers were provided with onsite professional
      development.

PMID- 24882882
TI  - Influence of Rigidity and Knot Complexity on the Knotting of Confined Polymers.
AB  - We employ computer simulations and thermodynamic integration to analyze the
      effects of bending rigidity and slit confinement on the free energy cost of tying
      knots, DeltaFknotting, on polymer chains under tension. A tension-dependent,
      nonzero optimal stiffness kappamin exists, for which DeltaFknotting is minimal.
      For a polymer chain with several stiffness domains, each containing a large
      amount of monomers, the domain with stiffness kappamin will be preferred by the
      knot. A local analysis of the bending in the interior of the knot reveals that
      local stretching of chains at the braid region is responsible for the fact that
      the tension-dependent optimal stiffness has a nonzero value. The reduction in
      DeltaFknotting for a chain with optimal stiffness relative to the flexible chain
      can be enhanced by tuning the slit width of the 2D confinement and increasing the
      knot complexity. The optimal stiffness itself is independent of the knot types we
      considered, while confinement shifts it toward lower values.

PMID- 24882883
TI  - Long-term behavior at foraging sites of adult female loggerhead sea turtles
      (Caretta caretta) from three Florida rookeries.
AB  - We used satellite telemetry to study behavior at foraging sites of 40 adult
      female loggerhead sea turtles (Caretta caretta) from three Florida (USA)
      rookeries. Foraging sites were located in four countries (USA, Mexico, the
      Bahamas, and Cuba). We were able to determine home range for 32 of the
      loggerheads. One turtle moved through several temporary residence areas, but the
      rest had a primary residence area in which they spent all or most of their time
      (usually >11 months per year). Twenty-four had a primary residence area that was
      <500 km2 (mean = 191). Seven had a primary residence area that was >=500 km2
      (range = 573-1,907). Primary residence areas were mostly restricted to depths
      <100 m. Loggerheads appeared to favor areas with larger-grained sediment (gravel
      and rock) over areas with smaller-grained sediment (mud). Short-term departures
      from primary residence areas were either looping excursions, typically involving
      1-2 weeks of continuous travel, or movement to a secondary residence area where
      turtles spent 25-45 days before returning to their primary residence area. Ten
      turtles had a secondary residence area, and six used it as an overwintering site.
      For those six turtles, the primary residence area was in shallow water (<17 m) in
      the northern half of the Gulf of Mexico (GOM), and overwintering sites were
      farther offshore or farther south. We documented long winter dive times (>4 h)
      for the first time in the GOM. Characterizing behaviors at foraging sites helps
      inform and assess loggerhead recovery efforts.

PMID- 24882884
TI  - Factors affecting the foraging behaviour of the European shag: implications for
      seabird tracking studies.
AB  - Seabird tracking has become an ever more popular tool to aid environmental
      procedures such as the designation of marine protected areas and environmental
      impact assessments. However, samples used are usually small and little
      consideration is given to experimental design and sampling protocol. European
      shags Phalacrocorax aristotelis were tracked using GPS technology over three
      breeding seasons and the following foraging trip characteristics: trip duration,
      trip distance, maximum distance travelled from the colony, size of area used and
      direction travelled from colony were determined for each foraging trip. The
      effect of sex, year of study, breeding site, number and age of chicks and the
      timing of tracking on foraging behaviour were investigated using a General
      Estimation Equation model. A range of sampling scenarios reflecting likely field
      sampling were also tested to compare how foraging behaviour differed depending on
      composition of the sample of birds tracked. Trip distance, trip duration, maximum
      distance travelled and size of area used were all significantly affected by the
      breeding site, and the number of chicks a tracked adult was raising. The effect
      of sex was also seen when examining trip distance, trip duration and the maximum
      distance travelled. The direction travelled on a foraging trip was also
      significantly affected by breeding site. This study highlights the importance of
      sampling regime and the influence that year, sex, age, number of chicks and
      breeding site can have on the foraging trip characteristics for this coastal
      feeding seabird. Given the logistical and financial constraints in tracking large
      numbers of individuals, this study identifies the need for researchers to
      consider the composition of their study sample to ensure any identified foraging
      areas are as representative as possible of the whole colony's foraging area.

PMID- 24882885
TI  - Estimating variation in surface emissivities of intertidal macroalgae using an
      infrared thermometer and the effects on temperature measurements.
AB  - Accurate measurements of surface temperatures with an infrared (IR) thermometer
      require input of the emissivities of the surfaces being measured; however, few
      determinations of the emissivities of intertidal organisms' surfaces have been
      made. Emissivities of intertidal macroalgae were measured to determine whether
      algal species, measurement angle, hydration, and layering affected them.
      Emissivities were similar and averaged 0.94 among 11 of 13 species. The species
      with lower and more variable emissivities (Chondracanthus exasperatus and
      Desmarestia viridis) differed in morphology from the other species, which were
      relatively flat thin blades with little surface texture. Measurement angle caused
      emissivities to decrease significantly in Mazzaella splendens but not in three
      other species. Hydration and layering of Ulva lactuca also had no effect. At 22 
      degrees C, measured temperatures were within 1  degrees C of actual temperatures
      when thermometer emissivity settings ranged from 0.75 to 1.00. When emissivities
      were set lower than actual values, measured temperatures were lower than actual
      temperatures at 15  degrees C and higher than actual temperatures at 60  degrees
      C. When the IR thermometer was used to measure surface temperatures of nine
      species of intertidal algae immediately before they were inundated by the
      incoming tide, temperatures were higher in mid intertidal than low intertidal
      individuals and higher on a sunnier day than an overcast day. Temperatures of U.
      lactuca increased with increasing height on the shore, but temperatures of
      Ulvaria obscura did not. Temperatures were also higher in Fucus distichus blades
      than receptacles, and lower in U. lactuca and M. splendens occurring in the lower
      layers of stacks of algae.

PMID- 24882886
TI  - Enhancement and Civic Virtue.
AB  - Opponents of biomedical enhancement frequently adopt what Allen Buchanan has
      called the Personal Goods Assumption. On this assumption, the benefits of
      biomedical enhancement will accrue primarily to those individuals who undergo
      enhancements, not to wider society. Buchanan has argued that biomedical
      enhancements might in fact have substantial social benefits by increasing
      productivity. We outline another way in which enhancements might benefit wider
      society: by augmenting civic virtue and thus improving the functioning of our
      political communities. We thus directly confront critics of biomedical
      enhancement who argue that it will lead to a loss of social cohesion and a
      breakdown in political life.

PMID- 24882887
TI  - Synthesis of 3-(1-Methyl-1H-imidazol-2-ylthio)propanoic Acid and (E)-3-(1-Methyl
      1H-imidazol-2-ylthio)acrylic Acid.
AB  - The syntheses of 3-(1-methyl-1H-imidazol-2-ylthio)acrylic acid and 3-(1-methyl-1H
      imidazol-2-ylthio)propanoic acid, mitochondria-targeted prodrugs of the
      antioxidant methimazole, are described. The method of Fan et al. (Fan et al.,
      Synthesis2006, 2286) for the reaction of phenols with propiolic acid and
      propiolate esters was modified to synthesize (E)-3-(1-methyl-1H-imidazol-2
      ylthio)acrylic acid. The intermediate tert-butyl (E)-3-(1-methyl-1H-imidazol-2
      ylthio)acrylate was prepared by the reaction of tert-butyl propiolate with
      methimazole; the use of tert-butyl propiolate rather than methyl propiolate gave
      tert-butyl (E)-3-(1-methyl-1H-imidazol-2-ylthio)acrylate as the predominant
      isomer. Acid hydrolysis of the intermediate ester afforded the target compound. 3
      (1-Methyl-1H-imidazol-2-ylthio)propanoic acid was synthesized from 3
      bromopropanoic acid and methimazole under conditions that gave preferential
      substitution on sulfur and minimized substitution on nitrogen.

PMID- 24882888
TI  - Concise total synthesis of (+/-)-actinophyllic acid.
AB  - A concise total synthesis of the complex indole alkaloid (+/-)-actinophyllic acid
      was accomplished by a sequence of reactions requiring only 10 steps from readily
      available, known starting materials. The approach featured a Lewis acid-catalyzed
      cascade of reactions involving stabilized carbocations that delivered the
      tetracyclic core of the natural product in a single chemical operation. Optimal
      conversion of this key intermediate into (+/-)-actinophyllic acid required
      judicious selection of a protecting group strategy.

PMID- 24882889
TI  - A concise synthesis of highly substituted imidazoles via copper-mediated
      oxidative C-H functionalization.
AB  - We herein report a simple and concise route for the synthesis of highly
      substituted imidazole derivatives via copper-mediated oxidative C-H
      functionalization in good to high yields. The advantage of the reaction lies in
      its mild reaction conditions and readily available starting materials.

PMID- 24882892
TI  - Introduction to Special Issue of Community College Review: Skills and
      Trajectories of Developmental Education Learners.

PMID- 24882890
TI  - Synthesis and Tautomerism of Spiro-Pyrazolines.
AB  - An experimental study on the synthesis, tautomerism and acid promoted structural
      changes of spiro-pyrazolines is described. The target was achieved through a
      [3+2]-dipolar cycloaddition of an alkene with nitrile imines generated in situ
      and was isolated in high yield. The synthesized cycloadduct displayed a tendency
      to exhibit an imine-enamine type of tautomerism as evidenced by X-ray crystal and
      NMR studies. Furthermore, addition of an acid resulted in the transformation of
      an imine tautomer to an enamine. The current report constitutes a first formal
      observation of this kind of tautomerism observed in spiro-indoline pyrazolines.

PMID- 24882893
TI  - Expediting Clinical and Translational Research via Bayesian Instrument
      Development.
AB  - Developing valid and reliable instruments is crucial but costly and time
      consuming in health care research and evaluation. The Food and Drug
      Administration and the National Institutes of Health have set up guidelines for
      developing patient-reported outcome instruments. However, the guidelines are not
      applicable to cases of small sample sizes. Instead of using an exact estimation
      procedure to examine psychometric properties, our Bayesian Instrument Development
      (BID) method integrates expert data and participant data into a single seamless
      analysis. Using a novel set of priors, we use simulated data to compare BID to
      classical instrument development procedures and test the stability of BID. To
      display BID to non-statisticians, a graphical user interface based on R and
      WINBUGS is developed and demonstrated with data on a small sample of heart
      failure patients. Costs were saved by eliminating the need for unnecessary
      continuation of data collection for larger samples as required by the classical
      instrument development approach.

PMID- 24882891
TI  - Multi-Parameter Exploration of HIV-1 Virus-Like Particles as Neutralizing
      Antibody Immunogens in Guinea Pigs, Rabbits and Macaques.
AB  - Virus-like particles (VLPs) offer a platform to test the hypothesis that, since
      antibody binding to native envelope glycoprotein (Env) trimers results in HIV-1
      neutralization, that native Env trimers presented in membranes may be useful for
      inducing neutralizing antibodies (nAbs) in a vaccine setting. So far, VLPs have
      not fulfilled this potential. Here, using a "shotgun" approach, we evaluated a
      wide cross-section of variables in a series of VLP immunizations. We identified 3
      tentative leads. First, that VLP doses may not have been sufficient for optimal
      nAb induction. Second, that dampening the antigenicity of non-functional Env (for
      example uncleaved gp160) using either protease digests or IgG masking may be
      useful. Third, that guinea pig sera preferentially target non-conserved epitopes
      and exhibit relatively high background activity, suggesting that rabbits may be
      preferable as small animal vaccine models. Recent immunogenicity studies in
      rabbits appear to bear out all 3 of these leads.

PMID- 24882894
TI  - The MSLT: More objections than benefits as a diagnostic gold standard?

PMID- 24882895
TI  - Seeing the forest through the trees.

PMID- 24882897
TI  - Sleep education and the importance of starting early.

PMID- 24882896
TI  - Back to basics regarding upper airway obstruction during sleep-size matters.

PMID- 24882898
TI  - Challenges in diagnosing narcolepsy without cataplexy: a consensus statement.
AB  - BACKGROUND: Diagnosing narcolepsy without cataplexy is often a challenge as the
      symptoms are nonspecific, current diagnostic tests are limited, and there are no
      useful biomarkers. In this report, we review the clinical and physiological
      aspects of narcolepsy without cataplexy, the limitations of available diagnostic
      procedures, and the differential diagnoses, and we propose an approach for more
      accurate diagnosis of narcolepsy without cataplexy. METHODS: A group of clinician
      scientists experienced in narcolepsy reviewed the literature and convened to
      discuss current diagnostic tools, and to map out directions for research that
      should lead to a better understanding and more accurate diagnosis of narcolepsy
      without cataplexy. RECOMMENDATIONS: To aid in the identification of narcolepsy
      without cataplexy, we review key indicators of narcolepsy and present a
      diagnostic algorithm. A detailed clinical history is mainly helpful to rule out
      other possible causes of chronic sleepiness. The multiple sleep latency test
      remains the most important measure, and prior sleep deprivation, shift work, or
      circadian disorders should be excluded by actigraphy or sleep logs. A short REM
      sleep latency (<= 15 minutes) on polysomnography can aid in the diagnosis of
      narcolepsy without cataplexy, although sensitivity is low. Finally, measurement
      of hypocretin levels can helpful, as levels are low to intermediate in 10% to 30%
      of narcolepsy without cataplexy patients.

PMID- 24882899
TI  - Narcolepsy and predictors of positive MSLTs in the Wisconsin Sleep Cohort.
AB  - STUDY OBJECTIVES: To study whether positive multiple sleep latency tests (MSLTs,
      mean sleep latency [MSL] <= 8 minutes, >= 2 sleep onset REM sleep periods
      [SOREMPs]) and/or nocturnal SOREMP (REM sleep latency <= 15 minutes during
      nocturnal polysomonography [NPSG]) are stable traits and can reflect incipient
      narcolepsy. DESIGN AND SETTING: Cross-sectional and longitudinal investigation of
      the Wisconsin Sleep Cohort Study. PARTICIPANTS: Adults (44% females, 30-81 years)
      underwent NPSG (n = 4,866 in 1,518 subjects), and clinical MSLT (n = 1,135), with
      823 having a repeat NPSG-MSLT at 4-year intervals, totaling 1725 NPSG with MSLT
      studies. Data were analyzed using linear mixed-effects models, and the stability
      of positive MSLTs was explored using kappa statistics. MEASUREMENTS AND RESULTS:
      Prevalence of a nocturnal SOREMP on a NPSG, of >= 2 SOREMPs on the MSLT, of MSL
      <= 8 minutes on the MSLT, and of a positive MSLT (MSL <= 8 minutes plus >= 2
      SOREMPs) were 0.35%, 7.0%, 22%, and 3.4%, respectively. Correlates of a positive
      MSLT were shift work (OR = 7.8, P = 0.0001) and short sleep (OR = 1.51/h, P =
      0.04). Test-retest for these parameters was poor, with kappa < 0.2 (n.s.) after
      excluding shift workers and short sleepers. Excluding shift-work, short sleep,
      and subjects with negative MSLTs, we found one undiagnosed subject with possible
      cataplexy (>= 1/month) and a NPSG SOREMPs; one subject previously diagnosed with
      narcolepsy without cataplexy with 2 NPSG SOREMPs and a positive MSLT, and two
      subjects with 2 independently positive MSLTs (66% human leukocyte antigen [HLA]
      positive). The proportions for narcolepsy with and without cataplexy were 0.07%
      (95% CI: 0.02-0.37%) and 0.20% (95% CI: 0.07-0.58%), respectively. CONCLUSIONS:
      The diagnostic value of multiple sleep latency tests is strongly altered by shift
      work and to a lesser extent by chronic sleep deprivation. The prevalence of
      narcolepsy without cataplexy may be 3-fold higher than that of narcolepsy
      cataplexy.

PMID- 24882900
TI  - A randomized, double-blind, placebo-controlled trial of eszopiclone for the
      treatment of insomnia in patients with chronic low back pain.
AB  - STUDY OBJECTIVES: Insomnia, which is very common in patients with chronic low
      back pain (LBP), has long been viewed as a pain symptom that did not merit
      specific treatment. Recent data suggest that adding insomnia therapy to pain
      targeted treatment should improve outcome; however, this has not been empirically
      tested in LBP or in any pain condition treated with a standardized pain
      medication regimen. We sought to test the hypothesis that adding insomnia therapy
      to pain-targeted treatment might improve sleep and pain in LBP. DESIGN: Double
      blind, placebo-controlled, parallel-group, 1-mo trial. SETTING: Duke University
      Medical Center Outpatient Sleep Clinic. PATIENTS: Fifty-two adult volunteers with
      LBP of at least 3 mo duration who met diagnostic criteria for insomnia (mean age:
      42.5 y; 63% females). INTERVENTIONS: Subjects were randomized to eszopiclone
      (ESZ) 3 mg plus naproxen 500 mg BID or matching placebo plus naproxen 500 mg
      twice a day. MEASUREMENTS AND RESULTS: ESZ SIGNIFICANTLY IMPROVED TOTAL SLEEP
      TIME (MEAN INCREASE: ESZ, 95 min; placebo, 9 min) (primary outcome) and nearly
      all sleep measures as well as visual analog scale pain (mean decrease: ESZ, 17
      mm; placebo, 2 mm) (primary pain outcome), and depression (mean Hamilton
      Depression Rating Scale improvement ESZ, 3.8; placebo, 0.4) compared with
      placebo. Changes in pain ratings were significantly correlated with changes in
      sleep. CONCLUSIONS: The addition of insomnia-specific therapy to a standardized
      naproxen pain regimen significantly improves sleep, pain, and depression in
      patients with chronic low back pain (LBP). The findings indicate the importance
      of administering both sleep and pain-directed therapies to patients with LBP in
      clinical practice and provide strong evidence that improving sleep disturbance
      may improve pain. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT00365976.

PMID- 24882902
TI  - Increased sleep promotes survival during a bacterial infection in Drosophila.
AB  - STUDY OBJECTIVES: The relationship between sleep and immune function is not well
      understood at a functional or molecular level. We therefore used a genetic
      approach in Drosophila to manipulate sleep and evaluated effects on the ability
      of flies to fight bacterial infection. SETTING: Laboratory. PARTICIPANTS:
      Drosophila melanogaster. METHODS AND RESULTS: We used a genetic approach to
      transiently alter neuronal excitability in the mushroom body, a region in the
      central brain that is known to regulate sleep. Flies with increased sleep for up
      to two days prior to a bacterial infection showed increased resistance to the
      infection and improved survival. These flies also had increased expression levels
      of a subset of anti-microbial peptide mRNA prior to infection, as well as
      increased NFkappaB activity during infection as indicated by in vivo luciferase
      reporter activity. In contrast, flies that experienced reduced sleep for up to
      two days prior to infection had no effect on survival or on NFkappaB activity
      during infection. However, flies with reduced sleep showed an altered defense
      mechanism, such that resistance to infection was increased, but at the expense of
      reduced tolerance. This effect was dependent on environmental condition.
      CONCLUSIONS: Increasing sleep enhanced activity of an NFkappaB transcription
      factor, increased resistance to infection, and strongly promoted survival.
      Together, these findings support the hypothesis that sleep is beneficial to the
      host by maintaining a robust immune system.

PMID- 24882903
TI  - The effect of a daytime nap on priming and recognition tasks in preschool
      children.
AB  - STUDY OBJECTIVES: The beneficial effect of sleep on memory consolidation is
      widely accepted in the adult population and has recently been shown in children.
      However, the few available data almost exclusively refer to school-aged children.
      Here we explore the effect of a daytime nap on memory consolidation in a sample
      of preschool children. DESIGN: Subjects performed both a figures recognition task
      and a priming task, in order to differentiate effects on explicit and implicit
      memory. SETTING: Nursery school. PARTICIPANTS: Twenty-three children (mean age:
      52.6 +/- 8 mo; 13 males) participated in the study. INTERVENTION: After a study
      phase in which children had to name 40 pictures of objects and animals, each
      subject either took an actigraphically monitored nap or stayed awake. At retest,
      children were administered both an implicit and an explicit memory task.
      MEASUREMENTS AND RESULTS: The implicit memory task consisted of naming 40
      pictures presented at eight ascending levels of spatial filtering. The explicit
      memory task consisted of judging 40 pictures as old or new. The number of correct
      answers at the explicit recognition task was significantly higher in the nap
      compared to the wake condition, whereas priming effects did not differ between
      conditions. CONCLUSIONS: A positive role of sleep in explicit memory
      consolidation, similar to the one observed in the adult, was detected in our
      sample of preschool children. In contrast, our data suggest that implicit
      perceptual learning, involved in priming tasks, does not benefit from sleep.

PMID- 24882901
TI  - Memory reactivation during rapid eye movement sleep promotes its generalization
      and integration in cortical stores.
AB  - STUDY OBJECTIVES: Memory reactivation appears to be a fundamental process in
      memory consolidation. In this study we tested the influence of memory
      reactivation during rapid eye movement (REM) sleep on memory performance and
      brain responses at retrieval in healthy human participants. PARTICIPANTS: Fifty
      six healthy subjects (28 women and 28 men, age [mean +/- standard deviation]:
      21.6 +/- 2.2 y) participated in this functional magnetic resonance imaging (fMRI)
      study. METHODS AND RESULTS: Auditory cues were associated with pictures of faces
      during their encoding. These memory cues delivered during REM sleep enhanced
      subsequent accurate recollections but also false recognitions. These results
      suggest that reactivated memories interacted with semantically related
      representations, and induced new creative associations, which subsequently
      reduced the distinction between new and previously encoded exemplars. Cues had no
      effect if presented during stage 2 sleep, or if they were not associated with
      faces during encoding. Functional magnetic resonance imaging revealed that
      following exposure to conditioned cues during REM sleep, responses to faces
      during retrieval were enhanced both in a visual area and in a cortical region of
      multisensory (auditory-visual) convergence. CONCLUSIONS: These results show that
      reactivating memories during REM sleep enhances cortical responses during
      retrieval, suggesting the integration of recent memories within cortical
      circuits, favoring the generalization and schematization of the information.

PMID- 24882904
TI  - Tongue fat infiltration in obese versus lean Zucker rats.
AB  - STUDY OBJECTIVES: Obesity is the most important risk factor for obstructive sleep
      apnea (OSA), and the effects of obesity may be mediated by tongue fat. Our
      objective was to examine the effects of obesity on upper airway structures in
      obese (OBZ) and non-obese (NBZ) Zucker rats. DESIGN: Animal study. SETTING:
      Academic Medical Center. PARTICIPANTS: OBZ (638.2 +/- 39 g; 14.9 +/- 1.1 w) and
      age-matched NBZ Zucker (442.6 +/- 37 g, 15.1 +/- 1.5 w) rats. INTERVENTIONS:
      TONGUE FAT AND VOLUME AND WERE ASSESSED USING: in vivo magnetic resonance
      spectroscopy (MRS), magnetic resonance imaging including Dixon imaging for tongue
      fat volume, ex vivo biochemistry (fat quantification; triglyceride (mg)/tissue
      (g), and histology (Oil Red O stain). MEASUREMENTS AND RESULTS: MRS: overall OBZ
      tongue fat/water ratio was 2.9 times greater than NBZ (P < 0.002) with the
      anterior OBZ tongue up to 3.3 times greater than NBZ (P < 0.002). Biochemistry:
      Triglyceride (TG) in the tongue was 4.4 times greater in OBZ versus NBZ (P <
      0.0006). TG was greater in OBZ tongue (3.57 +/- 1.7 mg/g) than OBZ masseter
      muscle (0.28 +/- 0.1; P < 0.0001) but tongue and masseter TG were not different
      in NBZ rats (0.82 +/- 0.3 versus 0.28 +/- 0.1 mg/g, P = 0.67). Dixon fat volume
      was significantly increased in OBZ (56 +/- 15 mm3) versus NBZ (34 +/- 5 mm3, P <
      0.004). Histology demonstrated a greater degree of intracellular muscle fat and
      extramuscular fat infiltration in OBZ versus NBZ rats. CONCLUSIONS: Genetically
      obese rats had a large degree of fat infiltration in the tongue compared to both
      skeletal muscle and tongue tissues of the non-obese age-matched littermates. The
      significant fat increase and sequestration in the obese tongue may play a role in
      altered tongue neuromuscular function, tongue stiffness or metabolic function.

PMID- 24882906
TI  - Severity of obstructive sleep apnea is associated with cardiac troponin I
      concentrations in a community-based sample: data from the Akershus Sleep Apnea
      Project.
AB  - OBJECTIVES: Previous community-based studies have failed to demonstrate an
      independent association between OSA and circulating cardiac troponin
      concentrations, a marker of myocardial injury. However, these studies have used
      troponin assays with modest analytic sensitivity to detect low-level, chronic
      increments in troponin levels. Using a highly sensitive troponin I (hs-TnI)
      assay, we tested the hypothesis that the severity of OSA is associated with
      myocardial injury independently of comorbidities. DESIGN: Cross-sectional study.
      SETTING: Community-based. PARTICIPANTS: 514 subjects (54% men, age 48 +/- 11 y
      [mean +/- SD]). INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: hs-TnI
      concentrations were measured in fasting morning blood samples and 318
      participants (62%) had hs-TnI concentration above the limit of detection ([LoD]
      1.2 ng/L). The severity of OSA, expressed as the apnea-hypopnea index (AHI) and
      nocturnal hypoxemia, was assessed by in-hospital polysomnography. After
      adjustment for age, gender, estimated creatinine clearance, history of coronary
      artery disease and hypertension, smoking, diabetes mellitus, systolic blood
      pressure, heart rate, body mass index, left ventricular hypertrophy, and
      cholesterol ratio in multivariate linear regression models, higher AHI
      (standardized beta = 0.12, P = 0.006), lower mean SpO2 (beta = -0.13, P = 0.012)
      and higher percentage of total sleep time with SpO2 < 90% (beta = 0.12, P =
      0.011) were all associated with higher hs-TnI levels in separate models.
      Additional analyses with hs-TnI categorized in tertiles or using a different
      strategy for persons with hs-TnI levels below the LoD did not change the results.
      CONCLUSION: Increased obstructive sleep apnea (OSA) severity is independently
      associated with higher concentrations of hs-TnI, suggesting that frequent apneas
      or hypoxemia in OSA may cause low-grade myocardial injury.

PMID- 24882905
TI  - Effects of obstructive sleep apnea and obesity on exercise function in children.
AB  - STUDY OBJECTIVES: Evaluate the relative contributions of weight status and
      obstructive sleep apnea (OSA) to cardiopulmonary exercise responses in children.
      DESIGN: Prospective, cross-sectional study. Participants underwent anthropometric
      measurements, overnight polysomnography, spirometry, cardiopulmonary exercise
      function testing on a cycle ergometer, and cardiac doppler imaging. OSA was
      defined as >= 1 obstructive apnea or hypopnea per hour of sleep (OAHI). The
      effect of OSA on exercise function was evaluated after the parameters were
      corrected for body mass index (BMI) z-scores. Similarly, the effect of obesity on
      exercise function was examined when the variables were adjusted for OAHI.
      SETTING: Tertiary pediatric hospital. PARTICIPANTS: Healthy weight and obese
      children, aged 7-12 y. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Seventy-one
      children were studied. In comparison with weight-matched children without OSA,
      children with OSA had a lower cardiac output, stroke volume index, heart rate,
      and oxygen consumption (VO2 peak) at peak exercise capacity. After adjusting for
      BMI z-score, children with OSA had 1.5 L/min (95% confidence interval -2.3 to 
      0.6 L/min; P = 0.001) lower cardiac output at peak exercise capacity, but minute
      ventilation and ventilatory responses to exercise were not affected. Obesity was
      only associated with physical deconditioning. Cardiac dysfunction was associated
      with the frequency of respiratory-related arousals, the severity of hypoxia, and
      heart rate during sleep. CONCLUSIONS: Children with OSA are exercise limited due
      to a reduced cardiac output and VO2 peak at peak exercise capacity, independent
      of their weight status. Comorbid OSA can further decrease exercise performance in
      obese children.

PMID- 24882907
TI  - Evaluation of a sleep education program for low-income preschool children and
      their families.
AB  - STUDY OBJECTIVES: To evaluate a novel sleep education program for low-income
      preschool children and their families. DESIGN: Randomized trial of an educational
      intervention. SETTING: Community-based. PARTICIPANTS: Head Start preschool
      families (n = 152) in greater Lansing and Detroit, Michigan. INTERVENTIONS:
      Classrooms or Head Start sites were randomized to an intervention group (prompt
      intervention) versus a control group (delayed intervention). Parents attended a
      one-time, 45-min sleep education program and preschoolers received 2 w (320 total
      min) of classroom sleep curriculum. MEASUREMENTS: Parent knowledge, attitudes,
      self-efficacy, and beliefs were assessed as the primary outcomes just before the
      45-min sleep intervention, immediately postintervention, and approximately 1 mo
      postintervention. Parents reported their child's bedtimes and wake times on 7-day
      sleep diaries at baseline and at 1-mo follow-up. Average weeknight sleep
      durations and bedtimes served as secondary outcomes. RESULTS: Linear mixed models
      showed a time * treatment effect for parents' knowledge, attitudes, and self
      efficacy (each P < 0.05) but not beliefs. These improvements were found
      immediately postintervention but were not retained at 1-mo follow-up. Children in
      the intervention group improved their weeknight sleep duration at 1-mo follow-up
      by 30 min (11.0 +/- 0.9 h vs. 10.5 +/- 1.0 hours at baseline) compared to
      controls (10.4 +/- 0.9 h versus 10.5 +/- 0.9 h at baseline) (P = 0.04 for
      difference between groups). Children did not show statistically significant
      improvements in bedtime. CONCLUSIONS: Educational interventions in early
      childhood can have an effect on parents' sleep knowledge, attitudes, and self
      efficacy, and on children's sleep behavior. However, repeated exposure to the new
      information may be important for parents as well as their children.

PMID- 24882910
TI  - Asymptotics of Bonferroni for Dependent Normal Test Statistics.
AB  - The Bonferroni adjustment is sometimes used to control the familywise error rate
      (FWE) when the number of comparisons is huge. In genome wide association studies,
      researchers compare cases to controls with respect to thousands of single
      nucleotide polymorphisms. It has been claimed that the Bonferroni adjustment is
      only slightly conservative if the comparisons are nearly independent. We show
      that the veracity of this claim depends on how one defines "nearly."
      Specifically, if the test statistics' pairwise correlations converge to 0 as the
      number of tests tend to infinity, the conservatism of the Bonferroni procedure
      depends on their rate of convergence. The type I error rate of Bonferroni can
      tend to 0 or 1 - exp(-alpha) ~ alpha, depending on that rate. We show using
      elementary probability theory what happens to the distribution of the number of
      errors when using Bonferroni, as the number of dependent normal test statistics
      gets large. We also use the limiting behavior of Bonferroni to shed light on
      properties of other commonly used test statistics.

PMID- 24882908
TI  - Dissociating effects of global SWS disruption and healthy aging on waking
      performance and daytime sleepiness.
AB  - STUDY OBJECTIVE: To contrast the effects of slow wave sleep (SWS) disruption and
      age on daytime functioning. DESIGN: Daytime functioning was contrasted in three
      age cohorts, across two parallel 4-night randomized groups (baseline, two nights
      of SWS disruption or control, recovery sleep). SETTING: Sleep research
      laboratory. PARTICIPANTS: 44 healthy young (20-30 y), 35 middle-aged (40-55 y),
      and 31 older (66-83 y) men and women. INTERVENTIONS: Acoustic stimulation
      contingent on appearance of slow waves. MEASUREMENTS AND RESULTS: Cognitive
      performance was assessed before sleep latency tests at five daily time-points.
      SWS disruption resulted in less positive affect, slower or impaired information
      processing and sustained attention, less precise motor control, and erroneous
      implementation, rather than inhibition, of well-practiced actions. These
      performance impairments had far smaller effect sizes than the increase in daytime
      sleepiness and differed from baseline to the same extent for each age group. At
      baseline, younger participants performed better than older participants across
      many cognitive domains, with largest effects on executive function, response
      time, sustained attention, and motor control. At baseline, the young were
      sleepier than other age groups. CONCLUSIONS: SWS has been considered a potential
      mediator of age-related decline in performance, although the effects of SWS
      disruption on daytime functioning have not been quantified across different
      cognitive domains nor directly compared to age-related changes in performance.
      The data imply that two nights of SWS disruption primarily leads to an increase
      in sleepiness with minor effects on other aspects of daytime functioning, which
      are different from the substantial effects of age.

PMID- 24882909
TI  - Deepening sleep by hypnotic suggestion.
AB  - STUDY OBJECTIVES: Slow wave sleep (SWS) plays a critical role in body restoration
      and promotes brain plasticity; however, it markedly declines across the lifespan.
      Despite its importance, effective tools to increase SWS are rare. Here we tested
      whether a hypnotic suggestion to "sleep deeper" extends the amount of SWS.
      DESIGN: Within-subject, placebo-controlled crossover design. SETTING: Sleep
      laboratory at the University of Zurich, Switzerland. PARTICIPANTS: Seventy
      healthy females 23.27 +/- 3.17 y. INTERVENTION: Participants listened to an
      auditory text with hypnotic suggestions or a control tape before napping for 90
      min while high-density electroencephalography was recorded. MEASUREMENTS AND
      RESULTS: After participants listened to the hypnotic suggestion to "sleep deeper"
      subsequent SWS was increased by 81% and time spent awake was reduced by 67% (with
      the amount of SWS or wake in the control condition set to 100%). Other sleep
      stages remained unaffected. Additionally, slow wave activity was significantly
      enhanced after hypnotic suggestions. During the hypnotic tape, parietal theta
      power increases predicted the hypnosis-induced extension of SWS. Additional
      experiments confirmed that the beneficial effect of hypnotic suggestions on SWS
      was specific to the hypnotic suggestion and did not occur in low suggestible
      participants. CONCLUSIONS: Our results demonstrate the effectiveness of hypnotic
      suggestions to specifically increase the amount and duration of slow wave sleep
      (SWS) in a midday nap using objective measures of sleep in young, healthy,
      suggestible females. Hypnotic suggestions might be a successful tool with a lower
      risk of adverse side effects than pharmacological treatments to extend SWS also
      in clinical and elderly populations.

PMID- 24882911
TI  - Simulation of reaction diffusion processes over biologically relevant size and
      time scales using multi-GPU workstations.
AB  - Simulation of in vivo cellular processes with the reaction-diffusion master
      equation (RDME) is a computationally expensive task. Our previous software
      enabled simulation of inhomogeneous biochemical systems for small bacteria over
      long time scales using the MPD-RDME method on a single GPU. Simulations of larger
      eukaryotic systems exceed the on-board memory capacity of individual GPUs, and
      long time simulations of modest-sized cells such as yeast are impractical on a
      single GPU. We present a new multi-GPU parallel implementation of the MPD-RDME
      method based on a spatial decomposition approach that supports dynamic load
      balancing for workstations containing GPUs of varying performance and memory
      capacity. We take advantage of high-performance features of CUDA for peer-to-peer
      GPU memory transfers and evaluate the performance of our algorithms on state-of
      the-art GPU devices. We present parallel e ciency and performance results for
      simulations using multiple GPUs as system size, particle counts, and number of
      reactions grow. We also demonstrate multi-GPU performance in simulations of the
      Min protein system in E. coli. Moreover, our multi-GPU decomposition and load
      balancing approach can be generalized to other lattice-based problems.

PMID- 24882912
TI  - A comparison of representations for discrete multi-criteria decision problems.
AB  - Discrete multi-criteria decision problems with numerous Pareto-efficient solution
      candidates place a significant cognitive burden on the decision maker. An
      interactive, aspiration-based search process that iteratively progresses toward
      the most preferred solution can alleviate this task. In this paper, we study
      three ways of representing such problems in a DSS, and compare them in a
      laboratory experiment using subjective and objective measures of the decision
      process as well as solution quality and problem understanding. In addition to an
      immediate user evaluation, we performed a re-evaluation several weeks later.
      Furthermore, we consider several levels of problem complexity and user
      characteristics. Results indicate that different problem representations have a
      considerable influence on search behavior, although long-term consistency appears
      to remain unaffected. We also found interesting discrepancies between subjective
      evaluations and objective measures. Conclusions from our experiments can help
      designers of DSS for large multi-criteria decision problems to fit problem
      representations to the goals of their system and the specific task at hand.

PMID- 24882913
TI  - The Effect of Union Status at First Childbirth on Union Stability: Evidence from
      Eastern and Western Germany.
AB  - It is often assumed that cohabitation is much less stable than marriage. If
      cohabitation becomes more common among parents, children may be increasingly
      exposed to separation. However, little is known about how the proportion of
      cohabiting parents relates to their separation behavior. Higher shares of
      childbearing within cohabitation might reduce the proportion of negatively
      selected couples among cohabiting parents, which could in turn improve their
      union stability. This study focuses on parents who were cohabiting when they had
      their first child. It compares their union stability within a context in which
      they represent the majority or the minority. The German case is well-suited to
      this research goal because non-marital childbearing is common in eastern Germany
      (60 %) but not in western Germany (27 %). The data came from the German Family
      Panel (pairfam), and include 1,844 married and cohabiting mothers born in 1971
      1973 and 1981-1983. The empirical results suggest that the union stability of
      cohabiting mothers is positively related to their prevalence: survival curves
      showed that eastern German cohabiting mothers had a greater degree of union
      stability than their western German counterparts. This difference increased in
      the event-history model, which accounted for the particular composition of
      eastern German society, including the relatively low level of religious
      affiliation among the population. Controlling for unobserved heterogeneity did
      not change this result. In sum, these findings indicate that context plays an
      important role in the union stability of cohabiting parents.

PMID- 24882914
TI  - Self-structuring foods based on acid-sensitive low and high acyl mixed gellan
      systems to impact on satiety.
AB  - This study investigated the in vitro acid-induced gelation of mixed systems of
      two biopolymers; low acyl and high acyl gellan gum. Rheological and texture
      analysis showed that these mixed gels displayed textures that lay between the
      material properties exhibited for the low and high acyl variants. DSC analysis
      showed that mixtures of the low acyl and high acyl forms exhibit two separate
      conformational transitions at temperatures coincident with each of the individual
      biopolymers. Various metabolically relevant pH environments and hydrocolloid
      concentrations were investigated. These resulted in very different acid gelled
      structures, which were characterised by texture analysis. The structures of the
      acid gels were shown to depend upon the pH, hydrocolloid concentration and
      proportion of each biopolymer used during their production. A selection of these
      mixed gellan structures were assessed post-production in terms of their response
      to prolonged exposure to an acidic (pH 1), stomach-like, environment. This
      resulted in a significant increase in the gel strength, regardless of the
      biopolymer proportions. The high acyl gellan was less acid-sensitive, and
      subsequently no evidence of acid gelation was observed with high acyl gellan at a
      proportion greater than 60% of the total biopolymer. The findings presented here
      demonstrate that structuring as well as de-structuring of mixed gellan acid gels
      can be controlled in acidic environments similar to those that are present in the
      stomach after food consumption.

PMID- 24882915
TI  - Introduction to symposium on unmeasured heterogeneity in school transition
      models.
AB  - Researchers have used models of school transitions for over 30 years to describe
      inequality of educational opportunity and have contributed a number of important
      refinements and extensions. School transition models have the complication that
      the estimated effects of family background on the probability of continuing in
      school are affected by differential attrition on unobserved factors at earlier
      stages of schooling. The articles in this symposium present a variety of useful
      approaches to unobserved heterogeneity in school transition models. Investigators
      who use these approaches should attend to several issues: (1) models for school
      transitions may be used both descriptively (and are not therefore subject to any
      well-defined "bias") and as tools for causal inference. (2) The concept of bias
      presupposes an underlying experiment, structural model, or population model that
      would, in principle, define the corresponding unbiased parameters - yet these
      underlying models are difficult to specify for school transition models. (3)
      Unobserved determinants of whether individuals make school transitions may be
      both exogenous and endogenous with respect to the observed regressors in the
      model. Without a model of how unobserved heterogeneity arises, attempted
      "corrections" for unmeasured heterogeneity may yield misleading estimates of the
      effects of measured determinants of school continuation.

PMID- 24882916
TI  - Tungsten(VI) N-Heterocyclic Carbene Complexes: Synthetic, Structural, and
      Computational Study.
AB  - The reaction of WOCl4 with 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene
      (Idipp) leads to an orange solid whose spectroscopic data are consistent with the
      1:1 adduct [WOCl4(Idipp)]. Computational studies at the DFT level further support
      this formulation. Exposure of this compound to the atmosphere results in rapid
      hydrolysis to various imidazolium salts. If air diffuses very slowly into
      solutions of [WOCl4(Idipp)], it also undergoes slow hydrolysis to form
      [WO2Cl2(Idipp)]. This has been crystallographically characterized and is the
      first five-coordinate, 1:1 adduct of WO2Cl2. This complex has also been subject
      to DFT calculations, and its metal-ligand bonding has been explored. The carbene
      metal interaction is primarily sigma-donor in nature. The mechanism of the
      hydrolysis has also been probed by computational methods, revealing a plausible,
      low-energy reaction pathway.

PMID- 24882917
TI  - Expansion of the Ligand Knowledge Base for Chelating P,P-Donor Ligands (LKB-PP).
AB  - We have expanded the ligand knowledge base for bidentate P,P- and P,N-donor
      ligands (LKB-PP, Organometallics2008, 31, 1372-1383) by 208 ligands and
      introduced an additional steric descriptor (nHe8). This expanded knowledge base
      now captures information on 334 bidentate ligands and has been processed with
      principal component analysis (PCA) of the descriptors to produce a detailed map
      of bidentate ligand space, which better captures ligand variation and has been
      used for the analysis of ligand properties.

PMID- 24882918
TI  - Mononuclear Phenolate Diamine Zinc Hydride Complexes and Their Reactions With
      CO2.
AB  - The synthesis, characterization, and zinc coordination chemistry of the three
      proligands 2-tert-butyl-4-[tert-butyl (1)/methoxy (2)/nitro (3)]-6-{[(2'
      dimethylaminoethyl)methylamino]methyl}phenol are described. Each of the ligands
      was reacted with diethylzinc to yield zinc ethyl complexes 4-6; these complexes
      were subsequently reacted with phenylsilanol to yield zinc siloxide complexes 7
      9. Finally, the zinc siloxide complexes were reacted with phenylsilane to produce
      the three new zinc hydride complexes 10-12. The new complexes 4-12 have been
      fully characterized by NMR spectroscopy, mass spectrometry, and elemental
      analyses. The structures of the zinc hydride complexes have been probed using VT
      NMR spectroscopy and X-ray diffraction experiments. These data indicate that the
      complexes exhibit mononuclear structures at 298 K, both in the solid state and in
      solution (d8-toluene). At 203 K, the NMR signals broaden, consistent with an
      equilibrium between the mononuclear and dinuclear bis(MU-hydrido) complexes. All
      three zinc hydride complexes react rapidly and quantitatively with carbon
      dioxide, at 298 K and 1 bar of pressure over 20 min, to form the new zinc formate
      complexes 13-15. The zinc formate complexes have been analyzed by NMR
      spectroscopy and VT-NMR studies, which reveal a temperature-dependent monomer
      dimer equilibrium that is dominated by the mononuclear species at 298 K.

PMID- 24882919
TI  - Synthesis and Characterization of Dimethylbis(2-pyridyl)borate Nickel(II)
      Complexes: Unimolecular Square-Planar to Square-Planar Rotation around
      Nickel(II).
AB  - The syntheses of novel dimethylbis(2-pyridyl)borate nickel(II) complexes 4 and 6
      are reported. These complexes were unambiguously characterized by X-ray analysis.
      In dichloromethane solvent, complex 4 undergoes a unique square-planar to square
      planar rotation around the nickel(II) center, for which activation parameters of
      DeltaH? = 12.2(1) kcal mol-1 and DeltaS? = 0.8(5) eu were measured via NMR
      inversion recovery experiments. Complex 4 was also observed to isomerize via a
      relatively slow ring flip: DeltaH? = 15.0(2) kcal mol-1; and DeltaS? = -4.2(7)
      eu. DFT studies support the experimentally measured rotation activation energy
      (cf. calculated DeltaH? = 11.1 kcal mol-1) as well as the presence of a high
      energy triplet intermediate (DeltaH = 8.8 kcal mol-1).

PMID- 24882920
TI  - The making of urban 'healtheries': the transformation of cemeteries and burial
      grounds in late-Victorian East London.
AB  - This paper focuses on the conversion of disused burial grounds and cemeteries
      into gardens and playgrounds in East London from around the 1880s through to the
      end of the century. In addition to providing further empirical depth, especially
      relating to the work of philanthropic organisations such as the Metropolitan
      Public Gardens Association, the article brings into the foreground debates
      regarding the importance of such spaces to the promotion of the physical and
      moral health of the urban poor. Of particular note here is the recognition that
      ideas about the virtuous properties of open, green space were central to the
      success of attempts at social amelioration. In addition to identifying the
      importance of such ideas to the discourse of urban sanitary reformers, the paper
      considers the significance of less virtuous spaces to it; notably here, the
      street. Building on Driver's work on 'moral environmentalism' and Osborne and
      Rose's on 'ethicohygienic space,' this paper goes on to explore the significance
      of habit to the establishing of what Brabazon called 'healtheries' in late
      Victorian East London.

PMID- 24882921
TI  - The material consumptive: domesticating the tuberculosis patient in Edwardian
      England.
AB  - The proliferation of general and specialist hospitals, lunatic asylums, and
      workhouse infirmaries in the nineteenth century challenged the popular perception
      of the home as a suitable site of health care. Amidst the emergence of yet
      another type of institution, the tuberculosis sanatorium, tuberculosis control in
      the Edwardian period was re-sited and re-scaled to accommodate what might be
      termed a 'preventive therapy' of domestic space. Three interlinked perspectives
      demonstrate why and how this happened. First, I explore the role of the national
      and local state in legitimating domestic space as a scale and a site for the
      regulation of tuberculosis patients and prevention of the disease. Second, I
      investigate how tuberculosis self-help manuals promoted a technology of the self
      that was founded largely on the principles of sanatorium therapy but was
      necessarily reconfigured to reflect the social relations of domestic space.
      Third, I assess the marketing of consumer goods to the domiciled tuberculosis
      sufferer through the pages of the British Journal of Tuberculosis. It is
      suggested that a common tubercular 'language' of material consumption was
      fashioned in order to normalise the accumulation of possessions for use in the
      home. These arguments are situated in relation to recent historical research on
      material culture and identity at the turn of the twentieth century, which has
      stressed the cultivation of individuality and that the right sort of possessions
      appropriately arranged in domestic space signified well-regulated morality.

PMID- 24882922
TI  - Associations of individual, household and environmental characteristics with
      carbon dioxide emissions from motorised passenger travel.
AB  - Carbon dioxide (CO2) emissions from motorised travel are hypothesised to be
      associated with individual, household, spatial and other environmental factors.
      Little robust evidence exists on who contributes most (and least) to travel CO2
      and, in particular, the factors influencing commuting, business, shopping and
      social travel CO2. This paper examines whether and how demographic, socio
      economic and other personal and environmental characteristics are associated with
      land-based passenger transport and associated CO2 emissions. Primary data were
      collected from 3474 adults using a newly developed survey instrument in the
      iConnect study in the UK. The participants reported their past-week travel
      activity and vehicle characteristics from which CO2 emissions were derived using
      an adapted travel emissions profiling method. Multivariable linear and logistic
      regression analyses were used to examine what characteristics predicted higher
      CO2 emissions. CO2 emissions from motorised travel were distributed highly
      unequally, with the top fifth of participants producing more than two fifth of
      emissions. Car travel dominated overall CO2 emissions, making up 90% of the
      total. The strongest independent predictors of CO2 emissions were owning at least
      one car, being in full-time employment and having a home-work distance of more
      than 10 km. Income, education and tenure were also strong univariable predictors
      of CO2 emissions, but seemed to be further back on the causal pathway than having
      a car. Male gender, late-middle age, living in a rural area and having access to
      a bicycle also showed significant but weaker associations with emissions
      production. The findings may help inform the development of climate change
      mitigation policies for the transport sector. Targeting individuals and
      households with high car ownership, focussing on providing viable alternatives to
      commuting by car, and supporting planning and other policies that reduce
      commuting distances may provide an equitable and efficient approach to meeting
      carbon mitigation targets.

PMID- 24882923
TI  - Results of endoscopic middle ear surgery for cholesteatoma treatment: a
      systematic review.
AB  - Traditional surgery for cholesteatoma of the middle ear is performed by
      microscopic approaches. However, in recent years endoscopic instrumentation,
      techniques and knowledge have greatly improved, and in our opinion endoscopic
      surgical techniques will gain increasing importance in otologic surgery in the
      future. The aim of this study was to focus on outcomes obtained using endoscopic
      surgery for the treatment of middle ear cholesteatoma. A systematic review of the
      literature was performed. A total of 7 articles comprising 515 patients treated
      exclusively with endoscope or with a combined technique were found. During post
      surgical follow-up, 48 (9.3%) patients showed a residual or recurrent pathology.
      Despite the small number of patients analyzed in our review, the outcomes of this
      technique appear to be promising. In particular, concerning the rates of
      recurrences and residual disease, endoscopic middle ear surgery appears to
      guarantee similar results in comparison to classic microscopic approaches with
      the advantage of performing minimally invasive surgery.

PMID- 24882924
TI  - OSAS and metabolic diseases: Round Table, 99(th) SIO National Congress, Bari
      2012.
AB  - This draft of the Official Round Table held during the 99th SIO National Congress
      is an updated review on the diagnostic tools, the importance of polysomnographic
      recording and a critical analysis of the surgical techniques in obstructive sleep
      apnoea syndrome (OSAS). The review and analysis of available publications is the
      premise along with a specific analysis of the relationship between OSAS and
      metabolic and vascular disorders. In addition, the most recent investigations on
      sleep disorders and altered glucose metabolism are summarised and discussed
      together with the results of a study by the authors involving a fairly large
      number of patients with OSAS and diabetes.

PMID- 24882925
TI  - Combined chemoradiotherapy with local microwave hyperthermia for treatment of
      T3N0 laryngeal carcinoma: a retrospective study with long-term follow-up.
AB  - The purpose of our study was to test the efficacy and toxicity of hyperthermia in
      conjunction with chemoradiotherapy for T3N0 laryngeal cancer. From 1997-2006, 25
      patients diagnosed with T3N0 laryngeal carcinoma who denied laryngectomy were
      selected for this retrospective study. Patients received a total dose of 70 Gy (2
      Gy per fraction, 5 days per week) in combination with 6 weekly sessions of
      hyperthermia, in addition to weekly cisplatin chemotherapy. The hyperthermia
      device was operated as a 433 MHz microwave heating with water loaded and water
      cooled waveguides. The temperature was monitored subcutaneously in the skin under
      the aperture of the waveguide. The median follow-up was 60 months, while 23 of 25
      patients (92%) presented complete response to treatment. The two patients that
      did not respond to thermoradiotherapy underwent total laryngectomy, and during
      follow-up were alive and free of disease. According to EORTC/RTOG criteria,
      toxicity was mild: three patients (12%) presented grade III, eight (32%)
      presented grade II and 14 (56%) presented grade I acute skin toxicity. Grade III
      laryngeal late toxicity (vocal cord malfunction due to severe oedema) was noted
      in two patients (8%) at 6-8 months post-thermo-chemoradiotherapy. Tmin was
      correlated (Spearman rho, p < 0.05) with response to treatment as well as with
      acute skin toxicity and laryngeal function. When a patient with T3N0 laryngeal
      carcinoma denies laryngectomy, an alternative treatment is combined thermo
      chemoradiotherapy which seems to be effective and generally tolerable with
      radiation-induced skin toxicity and/or late side effects. A larger patient cohort
      is needed to confirm these results. 

PMID- 24882926
TI  - Direct autofluorescence during CO2 laser surgery of the larynx: can it really
      help the surgeon?
AB  - Herein we assessed the impact of direct autofluorescence during intraoperative
      work-up on obtaining superficial free resection margins, identifying new areas of
      malignant transformation and altering disease-free survival and local control at
      3 years in patients submitted to transoral laser surgery (TLS) for early glottic
      cancer. Prospective cohort evaluation was carried out on the diagnostic accuracy
      of the superficial extent and TNM staging in 73 patients with glottic carcinoma
      undergoing transoral CO2 laser surgery. The use of direct autofluorescence was
      associated with superficial disease-free margins in 97.2% of cases, and with
      superficial close margins in 2.8%. The improvement in diagnostic accuracy was
      16.4%; in 8.2% of cases, there was upstaging of the TNM classification (in one
      case, a second neoplastic area in a different laryngeal site was observed and
      considered to be a second endolaryngeal primary). The sensitivity of direct
      autofluorescence was 96.5% with a specificity of 98.5%. Overall, 3-year disease
      specific survival and local control with laser alone were, respectively: T1a
      (97.5%, 100%), T1b (86.7%, 86.7%), T2 (88.9%, 88.9%). This study demonstrates
      that direct autofluorescence can help to identify positive superficial margins,
      and has a favourable impact on disease-specific survival and local control at 3
      years.

PMID- 24882927
TI  - Closure of the sigmoid sinus in lateral skull base surgery.
AB  - Closure of the sigmoid-jugular complex is generally planned during various
      surgical procedures on the skull base, either to repair a jugular foramen lesion
      or as the oncological boundary of the resection. A series of 218 cases of skull
      base tumour surgeries was analysed in which closure of the sigmoid-jugular
      complex was systematically planned (bilaterally in one case) in patients treated
      for jugular foramen paragangliomas, squamous cell carcinomas and other temporal
      bone tumours. Surgery was performed via a petro-occipital trans-sigmoid approach
      in 61 cases, an infratemporal A in 128, en bloc subtotal temporal bone resections
      in 10 and other approaches in 20. In our experience, planned unilateral (and, in
      one case, bilateral) closure of the sigmoid-jugular complex had no clinical
      consequences. The vicarious drainage of the skull base was always assessed
      preoperatively, revealing no contraindications to intraoperative sinus closure.
      Given the scarcity of literature on this subject, the present report shows that
      the procedure is associated with low morbidity and helps to improve our
      understanding of cerebral venous discharge.

PMID- 24882928
TI  - Anterior canal BPPV and apogeotropic posterior canal BPPV: two rare forms of
      vertical canalolithiasis.
AB  - Posterior canal benign paroxysmal positional vertigo (BPPV) is the most frequent
      form of BPPV. It is characterized by a paroxysmal positioning nystagmus evoked
      through Dix-Hallpike and Semont positioning tests. Anterior canal BPPV (AC) is
      more rare than posterior canal BPPV; it presents a prevalent down beating
      positioning nystagmus, with a torsional component clockwise for the left canal,
      counterclockwise for the right canal. Due to the possible lack of the torsional
      component, it is sometimes difficult to identify the affected ear. An
      apogeotropic variant of posterior BPPV (APC) has recently been described,
      characterised by a paroxysmal positional nystagmus in the opposite direction to
      the one evoked in posterior canal BPPV: the linear component is down-beating, the
      torsional component is clockwise for the right canal, counter-clockwise for the
      left canal, so that a contra-lateral anterior canal BPPV could be simulated.
      During a 16 month period, of 934 BPPV patients observed, the authors identified
      23 (2.5%) cases of apogeotropic posterior canal BPPV and 11 (1.2%) cases of
      anterior canal BPPV, diagnosed using the specific oculomotor patterns described
      in the literature. Anterior canal BPPV was treated with the repositioning
      manoeuvre proposed by Yacovino, which does not require identification of the
      affected side, whereas apogeotropic posterior canal BPPV was treated with the
      Quick Liberatory Rotation manoeuvre for the typical posterior canal BPPV, since
      in the Dix-Hallpike position otoliths are in the same position if they come
      either from the ampullary arm or from the non-ampullary arm. The direct
      resolution of BPPV (one step therapy) was obtained in 12/34 patients, 8/23
      patients with APC and 4/11 patients with AC; canalar conversion into typical
      posterior canal BPPV, later treated through Quick Liberatory Rotation (two-step
      therapy), was obtained in 19 patients,14/23 with APC and 5/11 with AC. Three
      patients were lost to follow-up. Considering the effects of therapeutic
      manoeuvres, the authors propose a grading system for diagnosis of AC and APC:
      "certain" when a canalar conversion in ipsilateral typical posterior canal BPPV
      is obtained; "probable" when APC or AC are directly resolved; "possible" when
      disease is not resolved and cerebral neuroimaging is negative for neurological
      diseases. Our results show that the oculomotor patterns proposed in the
      literature are effective in diagnosing APC and AC, and that APC is more frequent
      than AC. Both of these rare forms of vertical canal BPPV can be treated
      effectively with liberatory manoeuvres.

PMID- 24882930
TI  - Endoscopic ultrasonic curette-assisted removal of frontal osteomas.
AB  - Indications for endoscopic resection of fronto-ethmoidal osteomas have been
      progressively expanded thanks to optimization of surgical exposure and the
      development of dedicated instruments. Curved cutting drills are still suboptimal
      to treat hard osseous neoplasms of the frontal sinus. We present two patients
      affected by frontal osteoma treated with an endoscopic procedure using an
      ultrasonic bone curette. The ultrasonic bone curette may be considered an
      effective tool to reduce soft tissue manipulation, optimize surgical time and
      accelerate the healing process. However, the technique requires significant shape
      innovations to reach the lateral recesses and to manage pure intrasinusal
      lesions.

PMID- 24882929
TI  - The effect of the NMDA channel blocker memantine on salicylate-induced tinnitus
      in rats.
AB  - Short-term tinnitus develops shortly after the administration of a high dose of
      salicylate. Since salicylate selectively potentiates N-methyl- D-aspartate (NMDA)
      currents in spiral ganglion neurons, it may play a vital role in tinnitus by
      amplifying NMDA-mediated neurotransmission. The aim of this study was to
      determine whether systemic treatment with a NMDA channel blocker, memantine,
      could prevent salicylate-induced tinnitus in animals. Additional experiments were
      performed to evaluate the effect of memantine on the auditory brainstem response
      (ABR) and distortion product otoacoustic emissions (DPOAE) to test for changes in
      hearing function. Thirty-six rats were divided into 3 groups and treated daily
      for four consecutive days. One group (n = 12) was injected with salicylate (300
      mg/kg/d, IP), the second (n = 12) was treated with memantine (5 mg/kg/d, IP) and
      the third group (n = 12) was injected with salicylate and memantine. All rats
      were tested for tinnitus and hearing loss at 2, 24, 48 and 72 h after the first
      drug administration and 24 h post treatment; tinnituslike behaviour was assessed
      with gap prepulse inhibition of acoustic startle (GPIAS), and hearing function
      was measured with DPOAE, ABR and noise burst prepulse inhibition of acoustic
      startle (NBPIAS). Rats in the salicylate group showed impaired GPIAS indicative
      of transient tinnitus-like behaviour near 16 kHz that recovered 24 h after the
      last salicylate treatment. Memantine did not cause a significant change in GPIAS.
      Combined injection of salicylate and memantine significantly attenuated GPIAS
      tinnitus-like behaviour at 48 hours after the first injection. None of the
      treatments induced permanent threshold shifts in the ABR and DPOAE, which
      recovered completely within one day post treatment. Animals treated with
      salicylate plus memantine showed results comparable to animals treated with
      salicylate alone, confirming that there is no effect of memantine on DPOAE which
      reflects OHC function. The present study confirms the role of cochlear NMDA
      receptors in the induction of salicylate-induced tinnitus.

PMID- 24882931
TI  - The role of cricohyoidoepiglottopexy in the era of transoral laser surgery and
      radio/chemotherapy.

PMID- 24882932
TI  - Current trends for medico-legal disputes related to functional nasal surgery in
      Italy.
AB  - The problem of professional liability in case of adverse outcomes or failures
      secondary to surgery is very sensitive in many countries of the European
      Community. In Italy, a recent sentence of the Supreme Court concerning a patient
      who underwent septoplasty raised considerable doubts in relation to the guidance
      to be followed in disputes related to an alleged professional liability, further
      exacerbating the juridical orientation of recent years in this context. This
      ruling involves any surgery, as well as rhinologic surgery, and calls into
      question most regulatory and legal principles that have traditionally been
      adopted by the Italian Civil Law. The sentence states that the plaintiff is only
      required to document the failure of surgical treatment, but not the breach of the
      duty of care by the surgeon, thus shifting the burden of proof to the physician
      debtor. It also considers that, in assessing the degree of negligence, reference
      should be made to the qualifications of the surgeon, according to principles that
      are not covered by current regulations, denying that in general surgery (i.e.,
      not with aesthetic purposes) the surgeon must only to act with diligence and need
      not guarantee a favourable outcome. This series of statements, complementing one
      another and evolving more unfavourably towards physicians, facilitate legal
      disputes for speculative purposes through complainants, with obvious health and
      socio-economic implications.

PMID- 24882933
TI  - Papillary carcinoma on a thyroglossal duct cyst: diagnostic problems and
      therapeutic dilemma. A case report.
AB  - Thyroglossal duct cysts are one of the most common congenital abnormalities of
      the cervical region. Complications of these swellings are rare, and among these,
      appearance of a carcinoma has also been noted. We present a case of papillary
      carcinoma arising in a thyroglossal duct cyst in 20-year-old woman with a
      swelling of about 4 cm, located at the middle region of the neck over the hyoid
      bone. Our patient was treated using a modified Sistrunk operation, in which
      thyroidectomy proved crucial for the correct diagnosis and continuation of
      appropriate treatment. Our case confirms the difficulty in distinguishing a
      primitive thyroglossal duct carcinoma from a synchronous metastatic papillary
      carcinoma of the thyroid. This dilemma often remains unresolved.

PMID- 24882934
TI  - Adapting wheat in Europe for climate change.
AB  - Increasing cereal yield is needed to meet the projected increased demand for
      world food supply of about 70% by 2050. Sirius, a process-based model for wheat,
      was used to estimate yield potential for wheat ideotypes optimized for future
      climatic projections for ten wheat growing areas of Europe. It was predicted that
      the detrimental effect of drought stress on yield would be decreased due to
      enhanced tailoring of phenology to future weather patterns, and due to genetic
      improvements in the response of photosynthesis and green leaf duration to water
      shortage. Yield advances could be made through extending maturation and thereby
      improve resource capture and partitioning. However the model predicted an
      increase in frequency of heat stress at meiosis and anthesis. Controlled
      environment experiments quantify the effects of heat and drought at booting and
      flowering on grain numbers and potential grain size. A current adaptation of
      wheat to areas of Europe with hotter and drier summers is a quicker maturation
      which helps to escape from excessive stress, but results in lower yields. To
      increase yield potential and to respond to climate change, increased tolerance to
      heat and drought stress should remain priorities for the genetic improvement of
      wheat.

PMID- 24882935
TI  - Reducing the reliance on nitrogen fertilizer for wheat production.
AB  - All crops require nitrogen (N) for the production of a photosynthetically active
      canopy, whose functionality will strongly influence yield. Cereal crops also
      require N for storage proteins in the grain, an important quality attribute.
      Optimal efficiency is achieved by the controlled remobilization of canopy-N to
      the developing grain during crop maturation. Whilst N will always be required for
      crop production, targeting efficient capture and use will optimise consumption of
      this valuable macronutrient. Efficient management of N through agronomic practice
      and use of appropriate germplasm are essential for sustainability of agricultural
      production. Both the economic demands of agriculture and the need to avoid
      negative environmental impacts of N-pollutants, such as nitrate in water courses
      or release of N-containing greenhouse gases, are important drivers to seek the
      most efficient use of this critical agronomic input. New cultivars optimised for
      traits relating to N-use efficiency rather than yield alone will be required.
      Targets for genetic improvement involve maximising capture, partitioning and
      remobilization in the canopy and to the grain, and yield per se. Whilst there is
      existing genetic diversity amongst modern cultivars, substantial improvements may
      require exploitation of a wider germplasm pool, utilizing land races and
      ancestral germplasm.

PMID- 24882937
TI  - Can Childhood Factors Predict Workplace Deviance?
AB  - Compared to the more common focus on street crime, empirical research on
      workplace deviance has been hampered by highly select samples, cross-sectional
      research designs, and limited inclusion of relevant predictor variables that bear
      on important theoretical debates. A key debate concerns the extent to which
      childhood conduct-problem trajectories influence crime over the life-course,
      including adults' workplace crime, whether childhood low self-control is a more
      important determinant than trajectories, and/or whether each or both of these
      childhood factors relate to later criminal activity. This paper provides evidence
      on this debate by examining two types of workplace deviance: production and
      property deviance separately for males and females. We use data from the Dunedin
      Multidisciplinary Health and Development Study, a birth cohort followed into
      adulthood, to examine how childhood factors (conduct-problem trajectories and low
      self-control) and then adult job characteristics predict workplace deviance at
      age 32. Analyses revealed that none of the childhood factors matter for
      predicting female deviance in the workplace but that conduct-problem trajectories
      did account for male workplace deviance.

PMID- 24882936
TI  - Reducing the potential for processing contaminant formation in cereal products.
AB  - Processing contaminants may be defined as substances that are produced in a food
      when it is cooked or processed, are not present or are present at much lower
      concentrations in the raw, unprocessed food, and are undesirable either because
      they have an adverse effect on product quality or because they are potentially
      harmful. The presence of very low levels of processing contaminants in common
      foods is becoming an increasingly important issue for the food industry, as
      developments in analytical techniques and equipment bring foods under closer and
      closer scrutiny. This review considers the formation of lipid oxidation products,
      hydrogenation of polyunsaturated fatty acids to prevent lipid oxidation and the
      associated risk of trans fatty acid formation. The formation of acrylamide in the
      Maillard reaction is described, as well as the genetic and agronomic approaches
      being taken to reduce the acrylamide-forming potential of cereal grain. The
      multiple routes for the formation of furan and associated chemicals, including
      hydroxymethylfurfuryl, are also described. The evolving regulatory and public
      perception situations for these processing contaminants and their implications
      for the cereal supply chain are discussed, emphasising the need for cereal
      breeders to engage with the contaminants issue.

PMID- 24882939
TI  - Coccidial infection does not influence preening behavior in American goldfinches.
AB  - Preening behavior in birds is important for the maintenance of thermoregulatory
      and ornamental functions of plumage. It has been repeatedly demonstrated that
      birds trade off time between plumage maintenance and other activities. However,
      the condition-dependent constraints of preening remain virtually unstudied. Here,
      we present the first experimental test of the hypothesis that intestinal parasite
      infection impairs preening activity. We studied male American goldfinches (Spinus
      tristis), a species with carotenoid-based plumage coloration. Following pre
      alternate (spring) molt, we manipulated the health of males by infecting some
      birds with Isospora spp. coccidia and keeping others free of the infection.
      Although the goldfinches increased preening throughout the captive period, we
      found no significant effect of coccidial treatment on preening behavior. The
      effect of coccidia on plumage maintenance may be more pronounced under natural
      conditions where birds have limited access to food and engage in more activities
      that might limit time available for preening.

PMID- 24882938
TI  - The Problematic and Risky Internet Use Screening Scale (PRIUSS) for Adolescents
      and Young Adults: Scale Development and Refinement.
AB  - Problematic Internet use (PIU) is a growing health concern among adolescents and
      young adults. The purpose of this mixed-methods study was to develop and refine a
      theoretically-grounded and psychometrically-validated assessment instrument for
      PIU specifically tailored to adolescents and young adults. An item pool was
      developed using concept mapping and a review of the literature, and administered
      to 714 students from two universities between 18 and 25 years of age. Exploratory
      and confirmatory factor analyses were used in a development subsample (n=500) to
      construct the scale. A cross-validation sample (n=214) was used to confirm the
      scale's reliability. The Problematic and Risky Internet Use Screening Scale
      (PRIUSS) is an 18-item scale with three subscales: Social Impairment, Emotional
      Impairment, and Risky/Impulsive Internet Use. Based on its strong theoretical
      foundation and promising psychometric performance, the PRIUSS may be a valuable
      tool for screening and prevention efforts in this population.

PMID- 24882940
TI  - Evidence of a Continuum in Foundational Expressive Communication Skills.
AB  - Progress monitoring measurement is increasingly needed in early childhood to
      inform practitioners when an intervention change is needed and as a tool for
      accomplishing individualization and improving results for individual children.
      The Early Communication Indicator (ECI) is such a measure for infants and
      toddlers, 6 to 42 months of age. A greater understanding of the ECI key skills
      (i.e., gestures, vocalizations, single- and multiple-word utterances) could lead
      to further improvements in the sensitivity and utility of the decisions made
      compared to ECIs composite total communication score. Thus, we examined the
      pattern of growth within and between the ECI's four foundational skills in a
      large sample of children served in Early Head Start. Results confirmed a unique
      pattern of growth and change within each skill trajectory in terms of (a) age at
      skill onset and (b) peaks in each trajectory defining an inflection point or
      change from acceleration to deceleration. Analyses using these inflection points
      as intercepts with before and after trajectory slopes in a test of an adjacent
      skills temporal ordering growth model indicated good fit. Implications of a
      continuum of foundational ECI skills to future validation and decision making
      utility of the measure are discussed.

PMID- 24882941
TI  - Playing with Others: Head Start Children's Peer Play and Relations with
      Kindergarten School Competence.
AB  - Time-sampled observations of Head Start preschoolers' (N = 264; 51.5% boys; 76%
      Mexican American; M = 53.11 and SD = 6.15 months of age) peer play in the
      classroom were gathered during fall and spring semesters. One year later,
      kindergarten teachers rated these children's school competence. Latent growth
      models indicated that, on average, children's peer play was moderately frequent
      and increased over time during preschool. Children with higher initial levels or
      with higher slopes of peer play in Head Start had higher levels of kindergarten
      school competence. Results suggest that Head Start children's engagement with
      peers may foster development of skills that help their transition into formal
      schooling. These findings highlight the importance of peer play, and suggest that
      peer play in Head Start classrooms contributes to children's adaptation to the
      demands of formal schooling.

PMID- 24882942
TI  - Bottom-up and top-down dynamics in young children's executive function: Labels
      aid 3-year-olds' performance on the Dimensional Change Card Sort.
AB  - Executive function (EF) improves between the ages of 3 and 5 and has been
      assessed reliably using the Dimensional Change Card Sort (DCCS), a task in which
      children first sort bivalent cards by one dimension (e.g., shape) and then are
      instructed to sort by a different dimension (e.g., color). Three-year-olds
      typically perseverate on the pre-switch dimension, whereas 5-year-olds switch
      flexibly. Labeling task stimuli can facilitate EF performance (Jacques & Zelazo,
      2005; Kirkham, Cruess, & Diamond, 2003), but the nature of this effect is
      unclear. In 3 experiments we examined 2 hypotheses deriving from different
      theoretical perspectives: first, that labels facilitate performance in a more
      bottom-up fashion, by biasing attention to relevant task rules (Kirkham et al.,
      2003); and second, that labels aid performance in a more top-down fashion by
      prompting reflection and an understanding of the hierarchical nature of the task
      (Zelazo, 2004). Children performed better on the DCCS when labels referred to the
      relevant sorting dimension (Experiment 1). This was a function of the content of
      the labels rather than the change in auditory signal across phases (Experiment
      2). Furthermore, labeling the opposite dimension only did not have a
      symmetrically negative effect on performance (Experiment 3). Together, these
      results suggest external, verbal labels bias children to attend to task-relevant
      information, likely through interaction with emerging top-down, endogenous
      control.

PMID- 24882943
TI  - Wildfire-Migration Dynamics: Lessons from Colorado's Fourmile Canyon Fire.
AB  - The number of people living in wildfire prone wildland-urban interface (WUI)
      communities is on the rise. Yet, no prior study has investigated wildfire-induced
      residential relocation from WUI areas after a major fire event. To provide
      insight into the association between socio-demographic and socio-psychological
      characteristics and wildfire related intention to move, we use data from a survey
      of WUI residents in Boulder and Larimer Counties, Colorado. The data were
      collected two months after the devastating Fourmile Canyon fire destroyed 169
      homes and burned over 6,000 acres of public and private land. Although working
      with a small migrant sample, logistic regression models demonstrate that survey
      respondents intending to move in relation to wildfire incidence do not differ
      socio-demographically from their non-migrant counterparts. They do, however, show
      significantly higher levels of risk perception. Investigating destination choices
      shows a preference for short distance moves.

PMID- 24882944
TI  - Design of Functional Materials based on Liquid Crystalline Droplets.
AB  - This brief perspective focuses on recent advances in the design of functional
      soft materials that are based on confinement of low molecular weight liquid
      crystals (LCs) within micrometer-sized droplets. While the ordering of LCs within
      micrometer-sized domains has been explored extensively in polymer-dispersed LC
      materials, recent studies performed with LC domains with precisely defined size
      and interfacial chemistry have unmasked observations of confinement-induced
      ordering of LCs that do not follow previously reported theoretical predictions.
      These new findings, which are enabled in part by advances in the preparation of
      LCs encapsulated in polymeric shells, are opening up new opportunities for the
      design of soft responsive materials based on surface-induced ordering
      transitions. These materials are also providing new insights into the self
      assembly of biomolecular and colloidal species at defects formed by LCs confined
      to micrometer-sized domains. The studies presented in this perspective serve
      additionally to highlight gaps in knowledge regarding the ordering of LCs in
      confined systems.

PMID- 24882945
TI  - The forgotten grammatical category: Adjective use in agrammatic aphasia.
AB  - BACKGROUND: In contrast to nouns and verbs, the use of adjectives in agrammatic
      aphasia has not been systematically studied. However, because of the linguistic
      and psycholinguistic attributes of adjectives, some of which overlap with nouns
      and some with verbs, analysis of adjective production is important for testing
      theories of word class production deficits in agrammatism. AIMS: The objective of
      the current study was to compare adjective use in agrammatic and healthy
      individuals, focusing on three factors: overall adjective production rate,
      production of predicative and attributive adjectives, and production of
      adjectives with complex argument structure. METHOD & PROCEDURES: Narratives
      elicited from 14 agrammatic and 14 control participants were coded for open class
      grammatical category production (i.e., nouns, verbs, adjectives), with each
      adjective also coded for its syntactic environment (attributive/predicative) and
      argument structure. OUTCOMES & RESULTS: Overall, agrammatic speakers used
      adjectives in proportions similar to that of cognitively healthy speakers.
      However, they exhibited a greater proportion of predicative adjectives and a
      lesser proportion of attributive adjectives, compared to controls. Additionally,
      agrammatic participants produced adjectives with less complex argument structure
      than controls. CONCLUSIONS: The overall normal-like frequency of adjectives
      produced by agrammatic speakers suggests that agrammatism does not involve an
      inherent difficulty with adjectives as a word class or with predication, or that
      it entails a deficit in processing low imageability words. However, agrammatic
      individuals' reduced production of attributive adjectives and adjectives with
      complements extends previous findings of an adjunction deficit and of impairment
      in complex argument structure processing, respectively, to the adjectival domain.
      The results suggest that these deficits are not tied to a specific grammatical
      category.

PMID- 24882946
TI  - Macroecology Meets Macroeconomics: Resource Scarcity and Global Sustainability.
AB  - The current economic paradigm, which is based on increasing human population,
      economic development, and standard of living, is no longer compatible with the
      biophysical limits of the finite Earth. Failure to recover from the economic
      crash of 2008 is not due just to inadequate fiscal and monetary policies. The
      continuing global crisis is also due to scarcity of critical resources. Our
      macroecological studies highlight the role in the economy of energy and natural
      resources: oil, gas, water, arable land, metals, rare earths, fertilizers,
      fisheries, and wood. As the modern industrial technological-informational economy
      expanded in recent decades, it grew by consuming the Earth's natural resources at
      unsustainable rates. Correlations between per capita GDP and per capita
      consumption of energy and other resources across nations and over time
      demonstrate how economic growth and development depend on "nature's capital".
      Decades-long trends of decreasing per capita consumption of multiple important
      commodities indicate that overexploitation has created an unsustainable bubble of
      population and economy.

PMID- 24882947
TI  - Consumer acceptability of interventions to reduce Campylobacter in the poultry
      food chain.
AB  - Reducing human Campylobacter cases has become a priority for the UK Government.
      However the public's views on acceptability of interventions to reduce
      Campylobacter in poultry production are poorly understood in the UK and in other
      countries around the world. The objective of the study was to investigate how
      increasing awareness and knowledge changes consumer acceptability of
      interventions that reduce human campylobacteriosis in the poultry food chain.
      This approach is readily applicable to other risks and associated interventions.
      It involved a survey of the views of consumers in the Grampian region in North
      East Scotland. This found that better hygiene practices on farm, freezing chicken
      meat and vaccination of chickens were acceptable to the majority of participants
      (95%, 53% & 52% respectively) whilst irradiation and chemical wash of chicken
      meat were acceptable to <50%. Increasing consumer awareness by providing
      information on the Campylobacter disease burden in humans increased the number of
      participants finding them acceptable. However, chemical wash and irradiation
      remained the least acceptable interventions, although highly effective at
      reducing Campylobacter, and were found to be never acceptable to >50% of
      respondents. It was found on average that food poisoning concern, previous
      awareness of Campylobacter and living in rural or urban areas had either no or
      little effect effect on the acceptability of interventions. Further, previous
      awareness of Campylobacter did not influence consumer concern of harmful bacteria
      on chicken meat. Overall, findings indicate that increasing consumer
      acceptability of the most effective interventions is likely to be a difficult
      process.

PMID- 24882948
TI  - A Process Model of Parenting and Adolescents' Friendship Competence.
AB  - This study examined the prospective relationship between negative parenting
      behaviors and adolescents' friendship competence in a community sample of 416 two
      parent families in the Southeastern USA. Adolescents' externalizing problems and
      their emotional insecurity with parents were examined as mediators. Parents'
      psychological control was uniquely associated with adolescents' friendship
      competence. When both mediators were included in the same model, adolescents'
      perceptions of emotional insecurity in the parent-adolescent relationship fully
      mediated the association between parents' psychological control and adolescents'
      friendship competence. Parental hostility was associated with friendship
      competence indirectly through adolescents' emotional insecurity. Results
      contribute to identifying the mechanisms by which parenting affects youths'
      friendship competence, which is important in informing theory and practice
      regarding interpersonal relationships in adolescence.

PMID- 24882949
TI  - Clinical value of plasma soluble urokinase-type plasminogen activator receptor
      levels in term neonates with infection or sepsis: a prospective study.
AB  - BACKGROUND: suPAR, the soluble form of the urokinase-type plasminogen activator
      receptor, has been identified as a biomarker of infection in adults but its
      properties in neonatal infection are not known. METHODS: Plasma suPAR levels were
      determined by ELISA in 47 term neonates with infection (19 bacterial and 28
      viral) and in 18 healthy neonates as controls. Thirteen out of 47 infected
      neonates were septic. In all infected neonates, suPAR levels were repeated at 24
      hours, 48 hours, 3-5 days, and 7-10 days following admission. RESULTS: Plasma
      suPAR levels were significantly increased in infected neonates upon admission,
      whereas they were highest in septic neonates, in comparison with controls (P <
      0.001) and correlated positively with serum CRP levels (P = 0.001). At infection
      subsidence, suPAR concentrations decreased significantly in comparison with
      baseline (P < 0.001) but remained higher than in controls (P = 0.01). Receiver
      operating characteristic analysis resulted in significant areas under the curve
      for detecting either infected or septic neonates, but not for discriminating
      between bacterial and viral cause of infection. CONCLUSIONS: suPAR is a
      diagnostic biomarker of infection or sepsis in term neonates; however, it cannot
      discriminate bacterial from viral infections and also its utility for monitoring
      the response to treatment is questioned.

PMID- 24882950
TI  - Bronchoalveolar lavage fluid IFN-gamma+ Th17 cells and regulatory T cells in
      pulmonary sarcoidosis.
AB  - In sarcoidosis, increased Th17 cell fractions have been reported in
      bronchoalveolar lavage fluid, and elevated numbers of Th17 cells producing IFN-
      gamma have been observed in peripheral blood. The balance between Th1, Th17, and
      FoxP3(+) CD4(+) T cell subsets in sarcoidosis remains unclear. Bronchoalveolar
      lavage fluid cells, from 30 patients with sarcoidosis, 18 patients with other
      diffuse parenchymal lung diseases, and 15 healthy controls, were investigated
      with flow cytometry for intracellular expression of FoxP3. In a subset of the
      patients, expression of the cytokines IL17A and IFN- gamma was investigated. The
      fractions of FoxP3(+) CD4(+) T cells and Th17 cells were both lower in
      sarcoidosis compared to controls (P = 0.017 and P = 0.011, resp.). The proportion
      of Th17 cells positive for IFN- gamma was greater in sarcoidosis than controls
      (median 72.4% versus 31%, P = 0.0005) and increased with radiologic stage (N =
      23, rho = 0.45, and P = 0.03). IFN- gamma (+) Th17 cells were highly correlated
      with Th1 cells (N = 23, rho = 0.64, and P = 0.001), and the ratio of IFN- gamma
      (+) Th17/FoxP3(+) CD4(+) T cells was prominently increased in sarcoidosis. IFN-
      gamma (+) Th17 cells may represent a pathogenic subset of Th17 cells, yet their
      expression of IFN- gamma could be a consequence of a Th1-polarized cytokine
      milieu. Our results indicate a possible immune cell imbalance in sarcoidosis. 

PMID- 24882951
TI  - Outbreeding lethality between toxic Group I and nontoxic Group III Alexandrium
      tamarense spp. isolates: Predominance of heterotypic encystment and implications
      for mating interactions and biogeography.
AB  - We report the zygotic encystment of geographically dispersed isolates in the
      dinoflagellate species complex Alexandrium tamarense, in particular, successful
      mating of toxic Group I and nontoxic Group III isolates. However, hypnozygotes
      produced in Group I/III co-cultures complete no more than three divisions after
      germinating. Previous reports have suggested a mate recognition mechanism whereby
      hypnozygotes produced in co-cultures could arise from either homotypic (inbred)
      or heterotypic (outbred) gamete pairs. To determine the extent to which each
      occurs, a nested PCR assay was developed to determine parentage of individual
      hypnozygotes. The vast majority of hypnozygotes from pairwise Group I/III co
      cultures were outbred, so that inviability was a result of hybridization, not
      inbreeding. These findings support the assertion that complete speciation
      underlies the phylogenetic structure of the Alexandrium tamarense species
      complex. Additionally, the ribosomal DNA (rDNA) copy numbers of both hybrid and
      single ribotype hypnozygotes were reduced substantially from those of haploid
      motile cells. The destruction of rDNA loci may be crucial for the successful
      mating of genetically distant conjugants and appears integral to the process of
      encystment. The inviability of Group I/III hybrids is important for public health
      because the presence of hybrid cysts may indicate ongoing displacement of a
      nontoxic population by a toxic one (or vice versa). Hybrid inviability also
      suggests a bloom control strategy whereby persistent, toxic Group I blooms could
      be mitigated by introduction of nontoxic Group III cells. The potential for
      hybridization in nature was investigated by applying the nested PCR assay to
      hypnozygotes from Belfast Lough, Northern Ireland, a region where Group I and III
      populations co-occur. Two hybrid cysts were identified in 14 successful assays,
      demonstrating that Group I and III populations do interbreed in that region.
      However, an analysis of mating data collected over an 18-year period indicated a
      leaky pre-mating barrier between ribosomal species (including Groups I and III).
      Whether the observed selectivity inhibits hybridization in nature is dependent on
      its mechanism. If the point of selectivity is the induction of gametogenesis,
      dissimilar ribotypes could interbreed freely, promoting displacement in cases
      where hybridization is lethal. If instead, selectivity occurs during the adhesion
      of gamete pairs, it could enable stable coexistence of A. tamarense species. In
      either case, hybrid inviability may impose a significant obstacle to range
      expansion. The nested PCR assay developed here is a valuable tool for
      investigation of interspecies hybridization and its consequences for the global
      biogeography of these important organisms.

PMID- 24882953
TI  - Isolation of IgG antibodies to Toxocara in ankylosing spondylitis patients with
      acute anterior uveitis.
AB  - PURPOSE: Since few reports had been published on the prevalence of toxocariasis
      in ankylosing spondylitis (AS) patients with acute non-granulomatous anterior
      uveitis (ANGAU), the aim of this work was to determine the presence of antibodies
      against Toxocara canis in AS patients with ANGAU. METHODS: Thirty-six patients
      (14 female and 22 male) with AS were enrolled in the study. The history of ANGAU
      was accepted only if diagnosed by an ophthalmologist. The detection of IgG
      antibodies to T. canis was determined by enzyme-linked immunosorbent assay. In
      addition, antibodies to Ascaris lumbricoides were also tested to verify non
      specific reactions. RESULTS: The prevalence of ANGAU in the AS patients was 58%
      (21 / 36), and 38% (8 / 21) of the patients with ANGAU were positive for
      antibodies to Toxocara, while 7% (1 / 15) of AS patients without ANGAU were
      positive for T. canis (p = 0.038, two tails; mid-p exact). No antibodies were
      detected to A. lumbricoides antigens in the serum samples of patients with AS.
      CONCLUSIONS: These data suggest that the seroprevalence of antibodies to T. canis
      is high in Mexican patients with AS-associated uveitis, suggesting a chronic
      asymptomatic toxocariosis, which could be associated with the pathogenesis of
      ANGAU; however, further larger-scale studies are needed to confirm this
      observation.

PMID- 24882952
TI  - Korean guidelines for the diagnosis and management of dry eye: development and
      validation of clinical efficacy.
AB  - PURPOSE: To evaluate the clinical efficacy of newly developed guidelines for the
      diagnosis and management of dry eye. METHODS: This retrospective, multi-center,
      non-randomized, observational study included a total of 1,612 patients with dry
      eye disease who initially visited the clinics from March 2010 to August 2010.
      Korean guidelines for the diagnosis and management of dry eye were newly
      developed from concise, expert-consensus recommendations. Severity levels at
      initial and final visits were determined using the guidelines in patients with 90
      +/- 7 days of follow-up visits (n = 526). Groups with different clinical outcomes
      were compared with respect to clinical parameters, treatment modalities, and
      guideline compliance. Main outcome measures were ocular and visual symptoms,
      ocular surface disease index, global assessment by patient and physician, tear
      film break-up time, Schirmer-1 test score, ocular surface staining score at
      initial and final visits, clinical outcome after three months of treatment, and
      guideline compliance. RESULTS: Severity level was reduced in 47.37% of patients
      treated as recommended by the guidelines. Younger age (odd ratio [OR], 0.984; p =
      0.044), higher severity level at initial visit, compliance to treatment
      recommendation (OR, 1.832; p = 0.047), and use of topical cyclosporine (OR,
      1.838; p = 0.011) were significantly associated with improved clinical outcomes.
      CONCLUSIONS: Korean guidelines for the diagnosis and management of dry eye can be
      used as a valid and effective tool for the treatment of dry eye disease.

PMID- 24882954
TI  - Patient's self-recognition of reduced visual acuity due to recurrence of macular
      edema and prompt visitation to the hospital in retinal vein occlusion.
AB  - PURPOSE: To evaluate patients' self-recognition of reduced visual acuity due to
      recurring macular edema in retinal vein occlusion. METHODS: A retrospective
      review of medical records of patients who were diagnosed with recurring macular
      edema secondary to retinal vein occlusion was performed. The proportion of
      patients who recognized reduced visual acuity due to the recurrence of macular
      edema and who visited the hospital before the scheduled follow-up date was
      determined. Parameters including age, sex, diagnosis, visual acuity before
      recurrence of macular edema, and extent of visual acuity reduction due to
      recurrence of macular edema were compared in patients who recognized a reduction
      in visual acuity and those who did not. The proportion of patients who visited
      the hospital promptly was also determined. RESULTS: Forty eyes of 40 patients
      were included in the analysis. Sixteen and 24 patients were diagnosed with
      central retinal vein occlusion and branch retinal vein occlusion, respectively.
      Twenty-one patients (52.5%) recognized reduced visual acuity due to recurring
      macular edema. These patients were younger (59.2 +/- 7.6 vs. 64.8 +/- 9.4 years,
      p = 0.046), had better visual acuity before recurrence of macular edema (0.52 +/-
      0.48 vs. 1.02 +/- 0.46, p = 0.002), and exhibited a greater reduction in visual
      acuity after recurrence of macular edema (0.34 +/- 0.24 vs. 0.14 +/- 0.13, p =
      0.003). Only four patients visited the hospital before the scheduled follow-up
      date, and all of these patients lived relatively close to the hospital.
      CONCLUSIONS: For prompt treatment of recurring macular edema, more intensive
      education about the self-estimation of visual acuity is necessary, particularly
      for elderly patients who have relatively poor visual acuity. In addition, a
      simple and easy way to identify the recurrence of macular edema at the local
      clinic should be established for patients who live relatively far from the
      hospital.

PMID- 24882955
TI  - Changes in peripapillary retinal nerve fiber layer thickness after pattern
      scanning laser photocoagulation in patients with diabetic retinopathy.
AB  - PURPOSE: To examine the effects of panretinal photocoagulation (PRP) using a
      pattern scanning laser (PASCAL) system on the retinal nerve fiber layer (RNFL)
      thickness in patients with diabetic retinopathy. METHODS: This retrospective
      study included 105 eyes with diabetic retinopathy, which consisted of three
      groups: the PASCAL group that underwent PRP with the PASCAL method (33 eyes), the
      conventional group that underwent conventional PRP treatment (34 eyes), and the
      control group that did not receive PRP (38 eyes). The peripapillary RNFL
      thickness was measured by optical coherence tomography before, six months, and
      one year after PRP to evaluate the changes in peripapillary RNFL. RESULTS: The
      RNFL thickness in the PASCAL group did not show a significant difference after
      six months (average 3.7 times, p = 0.15) or one year after the PRP (average 3.7
      times, p = 0.086), whereas that in the conventional group decreased significantly
      after six months (average 3.4 times, p < 0.001) and one year after PRP (average
      3.4 times, p < 0.001). CONCLUSIONS: The results of this study suggest that the
      PASCAL system may protect against RNFL loss by using less energy than
      conventional PRP.

PMID- 24882956
TI  - The usefulness of interferon-gamma release assay for diagnosis of tuberculosis
      related uveitis in Korea.
AB  - PURPOSE: To evaluate the usefulness of the interferon-gamma release assay (IGRA)
      for diagnosing tuberculosis (TB)-related uveitis (TRU). METHODS: Records from 181
      patients with ocular signs and symptoms suggestive of TRU and intraocular
      inflammation of unknown etiology were reviewed. All subjects underwent clinical
      and laboratory testing, including IGRA, to rule out presence of underlying
      disease. A diagnosis of presumed TRU was made based on an internist's TB
      diagnosis and a patient's response to anti-TB therapy. Sensitivity, specificity,
      and positive predictive values of IGRA for TRU diagnosis were calculated.
      Clinical characteristics were compared between patients with positive and
      negative IGRA results. RESULTS: The sensitivity and specificity of IGRA for TRU
      were 100% and 72.0%, respectively. Mean age, percentage of patients with retinal
      vasculitis, and the anatomic type of uveitis were significantly different between
      patients with positive and negative IGRA results (all p <= 0.001). Positive IGRA
      rates and false-positive rates were significantly different between age and
      anatomic type groups (both p = 0.001). The positive predictive value of the IGRA
      among patients with intraocular inflammation was high (70%) when all of younger
      age (<= 40 years), posterior uveitis, and retinal vasculitis were present.
      CONCLUSIONS: The IGRA is useful for diagnosing TRU in the Korean population,
      especially when it is used as a screening test. Clinical characteristics,
      including younger age (<= 40 years), posterior uveitis, and retinal vasculitis in
      IGRA-positive patients, increase the likelihood of the patient having TRU.

PMID- 24882958
TI  - Symptom based diagnosis of infant under one year in outpatient clinic.
AB  - PURPOSE: We investigated chief complaints and ocular disorders in infants under
      one year of age and analyzed the association between complaints and disorders.
      METHODS: The medical records of 815 infants were reviewed. Chief complaints were
      grouped into the following 11 categories: eyelid drooping, epiphora (tearing),
      ocular discharge, lid swelling, eyelashes touching the eyeball, abnormalities of
      the anterior segment, abnormal eyeball movement (e.g., squint or nystagmus), red
      eye, trauma, poor eye contact, and miscellaneous. We performed ophthalmologic
      examinations at the doctors' discretion and analyzed the relationship between
      chief complaint and final diagnosis. RESULTS: Mean age of visiting the outpatient
      clinic was 6.09 +/- 3.07 months. The most common complaint was ocular discharge,
      followed by abnormal eyeball movement, epiphora, and eye redness. Among infants
      with ocular discharge, most were attributed to congenital nasolacrimal duct
      obstruction (155 infants) and conjunctivitis (75 infants). A total of 160
      guardians complained of abnormal eyeball movement and 86 of 160 infants (51.9%)
      suffered from pseudoesotropia. Additionally, exodeviation and esodeviation was
      found in 17.9% and 16.4% of infants, respectively. Eight guardian complained of
      poor eye contact in their infants and these infants were diagnosed with retinal
      disorders (3), congenital optic nerve disorders (2), cataract (1), glaucoma (1),
      and high hyperopia (1). CONCLUSIONS: The most common ocular symptoms in infants
      under one year of age included ocular discharge, epiphora, and eye redness.
      However, infants with poor eye contact or suspected abnormal eye movement should
      undergo a full ophthalmologic examination.

PMID- 24882957
TI  - Relationship between the lamina cribrosa, outer retina, and choroidal thickness
      as assessed using spectral domain optical coherence tomography.
AB  - PURPOSE: To evaluate the characteristics and relationship between peripapillary
      choroidal thickness (pCT), lamina cribrosa thickness (LCT), and peripapillary
      outer retinal layer thickness (pORT) as determined using spectral domain optical
      coherence tomography (SD-OCT) enhanced depth imaging (EDI). METHODS: In total,
      255 participants were included (87 healthy subjects, 87 glaucoma suspects (GS),
      and 81 glaucoma cases). The pORT, defined as the thickness between the posterior
      outer plexiform layer and the retinal pigment epithelium (RPE) interface, and the
      pCT, between the outer margin of the RPE and the choroidal-scleral interface,
      were manually measured using EDI scanning of the circumpapillary retinal nerve
      fiber layer (RNFL). LCT was determined by EDI scanning of the optic nerve head
      (ONH). Baseline characteristics, including axial length (AXL) and the SD-OCT
      measurements of the participants, were compared among the three groups. The
      correlation between putative factors and pCT was determined using univariate and
      multivariate linear regression analyses. RESULTS: In all three groups, both pORT
      and pCT were thinnest in the inferior area among the four quadrants. In the
      healthy group, the mean peripapillary RNFL, pORT, and LCT were significantly
      greater in comparison with those of the GS and glaucoma groups (p < 0.001, p <
      0.038, and p < 0.001, respectively). The pCT demonstrated no significant
      differences among the three groups (p = 0.083). Only age and AXL were associated
      with pCT by multivariate analysis. CONCLUSIONS: The pCT is substantially thinner
      in the inferior area of the ONH. In addition, the pCT demonstrates the strongest
      correlation with age and AXL, but was not associated with glaucoma or LCT.

PMID- 24882960
TI  - Topical prostaglandin analogue drugs inhibit adipocyte differentiation.
AB  - PURPOSE: To investigate the effects of topical prostaglandin analogue drugs on
      the differentiation of adipocytes. METHODS: Differentiation of 3T3-L1
      preadipocytes was induced with isobutylmethylxanthine, dexamethasone, and
      insulin. 3T3-L1 cells were exposed to 0.008, 0.08, 0.2 uM of latanoprost and
      travoprost. Reverse transcription polymerase chain reaction for mRNA expression
      of lipoprotein lipase and peroxisome proliferator-activated receptor gamma 2
      (PPARgamma2), and glycerol-3-phosphate dehydrogenase (G3PDH) assays were
      performed to examine the effects on early and late differentiation, respectively.
      Also, glycerol assays were done to evaluate the effect of prostaglandin analogues
      on lipolysis after differentiation. RESULTS: Both prostaglandin analogues
      inhibited differentiation of preadipocytes. Topical prostaglandin analogues
      significantly decreased G3PDH activity, a marker of late differentiation.
      However, topical prostaglandin analogues did not change mRNA expressions of
      lipoprotein lipase and PPARgamma2, markers of early differentiation. The
      activities of the early markers of differentiation were not changed significantly
      before and after growth arrest. Compared to latanoprost, travoprost decreased
      G3PDH activity more significantly (p < 0.05). Both prostaglandin analogues did
      not affect the lipolysis of differentiated adipocytes (p > 0.05). CONCLUSIONS:
      Prostaglandin analogues display an inhibitory effect on the differentiation of
      adipocytes when the cells start to differentiate especially in the late stage of
      differentiation. Thus, commercial topical prostaglandin analogues may decrease
      the fat contents of eyelids.

PMID- 24882961
TI  - Traumatic rupture of the superior oblique muscle tendon.
AB  - Traumatic rupture of the superior oblique muscle is rare. We report a case of a
      54-year-old man injured by the metal hook of a hanger, resulting in a rupture of
      the superior oblique muscle tendon. He complained of torsional diplopia when in
      the primary position. The distal margin of the superior oblique muscle was
      reattached to sclera 5 and 9 mm apart from the medial insertion of the superior
      rectus muscle. One week after the operation, torsional diplopia disappeared.
      However, a 4-prism diopter ipsilateral hypertropia was observed. Three months
      later, hypertropia gradually increased to 20 prism dioptors and the second
      operation was done to correct vertical diplopia. 

PMID- 24882959
TI  - Bone marrow-derived mesenchymal stem cells affect immunologic profiling of
      interleukin-17-secreting cells in a chemical burn mouse model.
AB  - PURPOSE: This study investigated interleukin (IL)-17-secreting cell involvement
      in sterile inflammation, and evaluated the effect of mesenchymal stem cells
      (MSCs) on IL-17-secreting cell immunologic profiling. METHODS: Twenty mice were
      sacrificed at time points of 6 hours, 1 day, 1 week, and 3 weeks (each group, n =
      5) after the cornea was chemically injured with 0.5N NaOH; IL-17 changes in the
      cornea were evaluated using enzyme-linked immunosorbent assay. Further, IL-17
      secreting cells were assessed in the cervical lymph nodes by a flow cytometer.
      Rat MSCs were applied intraperitoneally in a burn model (n = 10), IL-17-secreting
      T helper 17 (Th17) cell and non-Th17 cell changes were checked using a flow
      cytometer in both cornea and cervical lymph nodes at 1 week, and compared with
      those in the positive control (n = 10). RESULTS: IL-17 was highest in the cornea
      at 1 week, while, in the cervical lymph nodes, IL-17-secreting cells showed early
      increase at 6 hours, and maintained the increase through 1 day to 1 week, and
      levels returned to the basal level at 3 weeks. Specifically, the non-Th17 cells
      secreted IL-17 earlier than the Th17 cells. When the MSCs were applied, IL-17
      secretion was reduced in CD3(+)CD4(-)CD8(-), CD3(+)CD4(+)CD8(-), and CD3(+) CD4(
      )CD8(+) cells of the cervical lymph nodes by 53.7%, 43.8%, and 50.8%,
      respectively. However, in the cornea, IL-17 secretion of CD3(+)CD4(-)CD8(-) cells
      was completely blocked. CONCLUSIONS: The results indicated that both IL-17
      secreting non-Th17 and Th17 cells were involved in the chemical burn model, and
      MSCs appeared to mainly modulate non-Th17 cells and also partially suppress the
      Th17 cells.

PMID- 24882962
TI  - Bilateral macular hole following myopic photorefractive keratectomy.
AB  - A 42-year-old man was admitted to our clinic complaining of visual distortion in
      his left eye two months after bilateral myopic photorefractive keratectomy (PRK).
      Macular optical coherence tomography (OCT) showed a stage II macular hole in the
      left eye. Simultaneous OCT in the right eye showed vitreous traction and
      distortion of the outer retina. One month later, the patient underwent vitrectomy
      for the left eye, and the macular hole was closed. Two months after that, the
      patient complained of visual distortion in the right eye, and OCT revealed
      increased traction and accentuated outer retinal distortion indicating a stage IB
      macular hole. Traction attenuated later without any intervention. The short
      interval between PRK and hole formation, bilateral involvement, and the moderate
      refractive error in this case highlight the possible role of PRK in aggravating
      vitreoretinal interface abnormalities. We recommend the addition of PRK to the
      list of procedures that may be associated with the formation of a macular hole. 

PMID- 24882963
TI  - Proteus syndrome: report of a case with developmental glaucoma.
AB  - The purpose of this study was to report developmental glaucoma and
      pseudopapilledema in a patient with Proteus syndrome. We defined the presence of
      developmental glaucoma, right pseudopapilledema and myopia in a 4.5-year-old
      patient with Proteus syndrome. Marked right hemihypertrophy, lipoma,
      macrodactyly, and asymmetry of the limbs were observed on systemic examination. A
      cavernoma was also detected in magnetic resonance imaging of the brain. The
      patient underwent bilateral goniotomy surgery due to glaucoma. The surgical
      outcomes were satisfactory in both eyes. In conclusions developmental glaucoma
      and pseudopapilledema might be associated with Proteus syndrome. 

PMID- 24882964
TI  - Suspected bacterial endophthalmitis following sustained-release dexamethasone
      intravitreal implant: a case report.
AB  - A 58-year-old man admitted to our opthalmology department with the complaint of
      branch retinal vein occlusion. He was treated with intravitreal Ozurdex in the
      right eye. Two days after the injection, the patient presented with ocular pain
      and the visual acuity was hand movement. A diagnosis of endophthalmitis was made.
      We performed emergent pars plana vitrectomy (PPV) and the implant was removed
      from the vitreous cavity using a retinal forceps. A combination of vancomycin 1.0
      mg and amikacin 0.4 mg was injected intravitreally. However, because of the
      blurring in the vitreus one week after the procedure, phacoemulsification and a
      repeat PPV was performed. Five days after the last procedure the signs and
      symptoms of endophthalmitis were resolved. Our case demonstrated that
      endophthalmitis could develop after intravitreal implantation of Ozurdex.
      Surgical removal of the implant and immediate vitrectomy seems to be a useful
      treatment option in these cases.

PMID- 24882965
TI  - Unilateral punctate keratitis secondary to Wallenberg Syndrome.
AB  - We studied three patients who developed left unilateral punctate keratitis after
      suffering left-sided Wallenberg Syndrome. A complex evolution occurred in two of
      them. In all cases, neurophysiological studies showed damage in the trigeminal
      sensory component at the bulbar level. Corneal involvement secondary to
      Wallenberg syndrome is a rare cause of unilateral superficial punctate keratitis.
      The loss of corneal sensitivity caused by trigeminal neuropathy leads to
      epithelial erosions that are frequently unobserved by the patient, resulting in a
      high risk of corneal-ulcer development with the possibility of superinfection.
      Neurophysiological studies can help to locate the anatomical level of damage at
      the ophthalmic branch of the trigeminal nerve, confirming the suspected etiology
      of stroke, and demonstrating that prior vascular involvement coincides with the
      location of trigeminal nerve damage. In some of these patients, oculofacial pain
      is a distinctive feature.

PMID- 24882966
TI  - Correlations between Anti-Mast Cell Autoantibodies and Chronic Idiopathic
      Urticaria.
AB  - BACKGROUND: The etiology of chronic idiopathic urticaria (CIU) is not completely
      clear. There are a few antibodies were reported to correlate with CIU. OBJECTIVE:
      To investigate the correlation these antibodies and CIU. METHODS: The autologous
      serum skin test (ASST) and allergens were performed. Serum levels of
      immunoglobulin E (IgE), anti-FcepsilonRI and anti-IgE, anti-Helicobacter pylori
      (HP) antibodies and anti-thyroglobulin antibody (TGAb) were measured in 100
      patients with CIU, acute urticaria (AU) and normal controls respectively.
      RESULTS: Eighty-six percent food or inhalant allergens were detected in AU
      patients, but no allergens were detected in CIU patients and normal controls.
      Serum anti-FcepsilonRI antibody and anti-IgE antibody levels were higher in the
      CIU than that in the AU patients and normal controls (p<0.05, respectively). IgE
      level was lower in the CIU patients (T=190.00, p< 0.05), but increased in the AU
      patients (T=226.00, p<0.05) compared with the normal controls. The ASST positive
      rates in the CIU and the AU patients were 53.4% and 12.6% respectively, but all
      normal controls were negative. The anti-FcepsilonRI antibody level was higher in
      the ASST-positive CIU patients than those negative ones (T=101.73, p<0.05). In
      anti-HP antibody positive and TGAb positive CIU patients, anti-FcepsilonRI
      antibody positive rate was higher than AU patients (p<0.01) and normal controls
      (p<0.01). CONCLUSION: The anti-FcepsilonRI and anti-IgE antibodies play a key
      role in CIU, but anti-HP antibody and TGAb have an indirect correlation with CIU.

PMID- 24882967
TI  - Effect of emollients containing vegetable-derived lactobacillus in the treatment
      of atopic dermatitis symptoms: split-body clinical trial.
AB  - BACKGROUND: Atopic dermatitis (AD) patients suffer from xerosis. Proper skin
      care, including the use of emollients, may help improve xerosis and minimize
      disease exacerbation. Lactobacillus sakei probio 65, isolated from the Korean
      vegetable-based product kimchi, can decrease interleukin 4 and immunoglobulin E
      levels and inhibit Staphylococcus aureus. Moreover, it has reportedly shown
      positive dermatological effects in both animal and clinical studies. OBJECTIVE:
      To compare the effects of an emollient that contains Lactobacillus (treated) with
      a normal emollient (control) on AD. METHODS: This double-blind, randomized, split
      body clinical trial involved 28 patients with AD. The patients applied the
      Lactobacillus-containing emollient on one side of their body and the control
      emollient on the other side twice daily for 4 weeks. Trans-epidermal water loss
      (TEWL) and skin capacitance were evaluated and investigator global assessment and
      the visual analogue scale (VAS) were administered on weeks 0, 1, 2, and 4.
      RESULTS: The treated sides had significantly lower TEWL and VAS values and
      significantly higher skin capacitance values over time than the control sides.
      CONCLUSION: Topical application of Lactobacillus-containing emollients may
      improve the skin permeability of patients with AD.

PMID- 24882968
TI  - Pilot Study of the Efficacy of 578 nm Copper Bromide Laser Combined with
      Intralesional Corticosteroid Injection for Treatment of Keloids and Hypertrophic
      Scars.
AB  - BACKGROUND: Treatments including intralesional corticosteroid injection, pressure
      therapy, cryotherapy, and various laser therapies have had limited success for
      keloids and hypertrophic scars. OBJECTIVE: This trial evaluated the efficacy of a
      combination of 578 nm copper bromide laser and the more traditional intralesional
      corticosteroid injection for the treatment of keloids and hypertrophic scars with
      respect to scar color. METHODS: Keloids or hypertrophic scars of 12 Korean
      patients were treated five times by the combined treatment at 4-week intervals.
      Clinical improvement was assessed by the physicians' global assessment (PGA)
      comparing pre- and post-treatment photographs, as well as 4 weeks after the last
      treatment. Erythema intensity was quantified using a mexameter. RESULTS: Most
      scars showed significant clinical improvement in PGA and decreased erythema
      intensity after 5 treatments. All patients showed improvements in symptoms like
      pruritus. CONCLUSION: The combined treatment is effective for keloids and
      hypertrophic scars, especially when the telangiectatic portion of the scars is
      prominent. The adjunctive use of 578 nm copper bromide laser decreased the
      telangiectatic side effects of an intralesional corticosteroid injection by
      reducing the vascular components of scars.

PMID- 24882969
TI  - A clinicopathologic study of thirty cases of acquired perforating dermatosis in
      Korea.
AB  - BACKGROUND: Acquired perforating dermatosis (APD) is histopathologically
      characterized by transepidermal elimination of materials from the upper dermis.
      APD can be divided into four diseases: Kyrle's disease, perforating folliculitis,
      elastosis perforans serpiginosa, and reactive perforating collagenosis. APD is
      usually associated with systemic diseases, especially diabetes mellitus or
      chronic renal failure. So far, there have only been a few Korean studies of APD,
      which have a limited number of patients. OBJECTIVE: The aim of this study is to
      evaluate the clinical and histopathologic characteristics of 30 cases of APD and
      to examine the association with systemic diseases. METHODS: We retrospectively
      reviewed the medical records and biopsy specimens of 30 patients who were
      diagnosed with APD. RESULTS: The mean age was 55.5 years, and the average
      duration of the lesion was 7.8 months. The lower extremities (73.3%) were the
      most frequently occurring sites of the lesion. Twenty-five patients (83.3%) had
      pruritus, and Koebner's phenomenon was present in 11 patients. Patients of 63.3%
      had at least one systemic disease. Diabetes mellitus (n=17, 56.7%) and chronic
      renal failure (n=10, 33.3%) were the most commonly associated conditions. Most
      patients received topical steroids (93.3%) and antihistamines (80.0%). The most
      common histopathologic type was reactive perforating collagenosis (n=23, 73.3%).
      CONCLUSION: In this study, most patients had a systemic association to the
      diseases. Therefore, we suggest that further evaluation is necessary for patients
      who present with APD. This includes reviewing patient's comprehensive past
      medical history, clinical exam, and additional diagnostic testing to check for
      the possibility of associated systemic diseases.

PMID- 24882970
TI  - Intralesional methotrexate for the treatment of keratoacanthoma: retrospective
      study and review of the korean literature.
AB  - BACKGROUND: Although intralesional methotrexate (MTX) is an effective,
      nonsurgical treatment of keratoacanthoma (KA), there have not been many reports
      of on the MTX treatment for KA in Korea. OBJECTIVE: The purpose of this study was
      to evaluate the clinical efficacy of the intralesional MTX for the treatment of
      KA in Korean patients. METHODS: We retrospectively studied seven patients with KA
      who received intralesional injection of MTX in our department. The efficacy was
      evaluated based on the physician assessment. Our review also included the cases
      of KA treated with intralesional MTX in Korean patients from the previous
      reports. We then analyzed the therapeutic regimens in the Korean patients by
      comparing them with the Caucasian patients. RESULTS: We identified 11 cases of
      Korean KA patients treated with an intralesional MTX, including seven from our
      institution and four from the Korean literature. Ten of the 11 patients (91%)
      showed a complete resolution with an intralesional MTX. No adverse events were
      observed during the treatment and the follow-up periods. No recurrence was found
      during the follow-up. In therapeutic analysis, the Korean patients required 2 to
      7 injections (mean 4.6 injections) to achieve a tumor resolution with the mean
      time to clearing at 7.6 weeks. CONCLUSION: Intralesional MTX can be an effective
      and safe non-operative treatment modality for most Koreans with KA.

PMID- 24882971
TI  - Long-term survival analysis and clinical follow-up in acral lentiginous malignant
      melanoma undergoing sentinel lymph node biopsy in korean patients.
AB  - BACKGROUND: In cutaneous malignant melanoma (MM) with clinically uninvolved
      regional lymph nodes, sentinel lymph node (SLN) status is the most powerful
      indicator of both overall survival (OS) and disease-free survival (DFS). However,
      no studies on the long-term survival and clinical follow-up of Korean patients
      with acral lentiginous MM (ALM) undergoing SLN biopsy (SLNB) have been published.
      OBJECTIVE: The purpose of this study was to investigate the clinical prognosis
      and long-term survival of Korean patients with ALM according to SLN status.
      METHODS: Thirty-four ALM patients undergoing SLNB were included in this study. We
      evaluated clinical and histopathological follow-up data such as the stage of
      disease, treatment, recurrence, and metastasis, and analyzed OS and DFS according
      to SLN status. RESULTS: The median follow-up time was 60.5 months (range 3~127
      months). Positive SLNs were noted in 14 patients (41.2%). Patients with negative
      SLNs had better OS and DFS than those with positive SLNs (p<0.05). Increased
      Breslow thickness was associated with short OS and DFS (p<0.05), and female
      patients showed better DFS than male patients (p<0.05). CONCLUSION: To our
      knowledge, this is the first study on the long-term survival and clinical follow
      up of patients undergoing SLNB for ALM in Korea. Our findings show that SLN
      status is an important prognostic factor for predicting OS and DFS.

PMID- 24882972
TI  - A Prospective, Long-Term Follow-Up Study of 1,444 nm Nd:YAG Laser: A New Modality
      for Treating Axillary Bromhidrosis.
AB  - BACKGROUND: Surgery for bromhidrosis has a high risk of complications such as
      hematoma and necrosis. New nonsurgical methods may reduce the burden on surgery
      and the risks for the patient. OBJECTIVE: This study was performed to evaluate
      the efficacy and side-effects of the 1,444 nm Nd:YAG interstitial laser for
      treating axillary bromhidrosis. METHODS: Eighteen bromhidrosis patients were
      treated with a 1,444 nm Nd:YAG laser at Korea University Ansan Hospital. The post
      treatment follow-up was 6 months. After the procedure, we confirmed apocrine
      gland destruction through histopathological examination. At each follow-up, we
      measured the severity of the remaining odor, postoperative pain, degree of
      mobility restriction, and overall satisfaction. RESULTS: After 180 days of follow
      up, malodor elimination was good in 20 axillae, fair in 12 axillae, and poor in
      four axillae. At the end point of the study, 14 patients were totally satisfied
      with the laser treatment, three patients were partially satisfied, and one
      patient was disatisfied. Pain and limitation of mobility were significantly
      reduced within 1 week post-operatively, and were almost resolved within 4 weeks
      post-operatively. A histopathological examination revealed decreased density and
      significant alterations to the apocrine glands. CONCLUSION: Subdermal coagulation
      treatment with a 1,444 nm Nd:YAG interstitial laser may be a less invasive and
      effective therapy for axillary bromhidrosis.

PMID- 24882973
TI  - Clinical characteristics of cholinergic urticaria in Korea.
AB  - BACKGROUND: Cholinergic urticaria is a type of physical urticaria characterized
      by heat-associated wheals. Several reports are available about cholinergic
      urticaria; however, the clinical manifestations and pathogenesis are incompletely
      understood. OBJECTIVE: The purpose of this study was to investigate the clinical
      characteristics of cholinergic urticaria in Korea. METHODS: We performed a
      retrospective study of 92 patients with cholinergic urticaria who were contacted
      by phone and whose diagnoses were confirmed by the exercise provocation test
      among those who had visited The Catholic University of Korea, Catholic Medical
      Center from January 2001 to November 2010. RESULTS: All 92 patients were male,
      and their average age was 27.8 years (range, 17~51 years). Most of the patients
      had onset of the disease in their 20s and 30s. Non-follicular wheals were located
      on the trunk and upper extremities of many patients, and the symptoms were
      aggravated by exercise. Eight patients showed general urticaria symptoms and 15
      had accompanying atopic disease. Forty-three patients complained of seasonal
      aggravation. Most patients were treated with first and second-generation
      antihistamines. CONCLUSION: Dermatologists should consider these characteristics
      in patients with cholinergic urticaria. Further investigation and follow-up
      studies are necessary to better understand the epidemiological and clinical
      findings of cholinergic urticaria.

PMID- 24882974
TI  - Prognostic and Clinicopathologic Associations of BRAF Mutation in Primary Acral
      Lentiginous Melanoma in Korean Patients: A Preliminary Study.
AB  - BACKGROUND: In the majority of melanomas, the RAS/RAF/MEK/ERK signaling pathway
      is constitutively activated, due to oncogenic mutations in the BRAF and NRAS
      genes. The BRAF mutation has been mainly described in Caucasian melanomas.
      However, there is a lack of study evaluating the status, and the clinical
      significance, of BRAF mutation in the Asian population. OBJECTIVE: This study was
      aimed to determine the frequency of BRAF mutation, and to evaluate the
      correlation of BRAF status with clinicopathologic features and outcomes, in
      Korean primary acral lentiginous melanoma (ALM) patients. METHODS: ALM samples
      (n=36) were analyzed for the BRAF V600E mutation, by dual-priming oligonucleotide
      (DPO) based real-time polymerase chain reaction. The clinicopathologic features
      and prognosis of the patients were analyzed with BRAF mutation status. RESULTS:
      The incidence of BRAF V600E mutation was 19.4% (7/36). The BRAF V600E mutations
      were not associated with clinicopathologic features, except for the age factor.
      All of the BRAF-mutant patients survived without recurrence or metastasis, and
      have a better clinical outcome than BRAF wild-type patients. CONCLUSION: In
      Korean primary ALM, a low frequency of BRAF mutation was shown; and BRAF mutation
      presented with a favorable prognosis. These results indicate that other
      distinctive genetic mechanisms may have more important roles in the development
      and progression of disease. Further multicenter study with large sample size is
      firmly needed, to confirm the results of our preliminary study.

PMID- 24882975
TI  - Immunohistochemical Analysis of Interleukin-17 Producing T Helper Cells and
      Regulatory T Cells Infiltration in Annular Erythema Associated with Sjogren's
      Syndrome.
AB  - BACKGROUND: Peculiar erythema known as annular erythema associated with Sjogren's
      syndrome (AESS) can be differentiated from autoimmune annular erythema and
      subacute cutaneous lupus erythematosus, both clinically and histologically.
      However, there are no detailed investigations on immune competent cells
      infiltration. OBJECTIVE: Preferential infiltration of interleukin-17-producing T
      helper (Th17) cells and regulatory T (Treg) cells into the labial salivary gland
      is reported to play a role in maintaining mucoepithelitis in patients with
      Sjogren's syndrome. In this study, we evaluated Th17 and Treg cell infiltration
      into the lesional skin of AESS. METHODS: We analyzed the numbers and infiltration
      patterns of Th17 and FoxP3 (+) Treg cells in seven cases of AESS using
      immunohistochemistry. Seven patients with systemic lupus erythematosus (SLE),
      atopic dermatitis (AD) and psoriasis vulgaris (PV), which are representatives of
      Th17 cell-involved skin disorders, were enrolled as disease controls. RESULTS:
      Periappendageal and epidermal changes, such as follicular plugging and
      liquefaction, were evident in the annular erythema of SLE, not AESS, tissue
      samples. In AESS tissue samples, dense perivascular and periappendageal
      infiltration of lymph cells was observed in the middle-to-deep dermis, as
      previously described, in contrast to the superficial infiltration pattern
      observed in both AD and PV samples. While the total number of infiltrated
      lymphocytes was similar between AESS and SLE tissue samples, Th17 cells were
      found to be preferentially infiltrated in the middle-to-deep dermis in AESS
      samples. CONCLUSION: These results suggest that an increased number and
      distribution of infiltration of Th17 cells is a preferential feature of AESS,
      rather than a characteristic feature of annular erythema of SLE.

PMID- 24882976
TI  - Effect of adenosine on melanogenesis in b16 cells and zebrafish.
AB  - BACKGROUND: Adenosine is a nucleoside, in which an adenine molecule is attached
      to a ribofuranose sugar moiety. It can be released into the microenvironment by
      metabolically active cells, and then fulfills a multitude of functions in
      regulation of cell proliferation, by activating four subtypes of G protein
      coupled adenosine receptors. OBJECTIVE: In this study, we investigated the effect
      of adenosine on melanogenesis, using B16 melanoma cells. METHODS: The toxic
      effects of adenosine on B16 melanoma cells were assessed. To understand the
      mechanism of the effect of adenosine on melanogenesis in B16 cells, melanin
      content and tyrosinase activity were measured. Tyrosinase, tyrosinase-related
      protein-1, and dopachrome tautomerase were monitored by Western blotting.
      Finally, adenosine was applied to zebrafish embryos, and its in vivo effect on
      pigmentation investigated. RESULTS: At a low concentration, adenosine increased
      melanin content and tyrosinase activity, while a high dose of adenosine resulted
      in inhibition of tyrosinase activity. Western blotting showed that adenosine
      increased tyrosinase protein levels slightly, while high-dose adenosine decreased
      the expression of tyrosinase. In zebrafish tests, adenosine slightly inhibited
      body pigmentation. CONCLUSION: In this study, we investigated the effect of
      adenosine on melanogenesis, using the well-established B16 melanoma cell and
      zebrafish models. The results suggest that adenosine may inhibit pigmentation,
      through negative regulation of tyrosinase.

PMID- 24882977
TI  - Dermoscopic approach to a small round to oval hairless patch on the scalp.
AB  - BACKGROUND: Various kinds of alopecia can show small round or oval hairless
      patch. Dermoscopy could be a simple, useful tool for making a correct diagnosis.
      OBJECTIVE: The aim of this study is to investigate clinical usefulness of
      dermoscopy for diseases with small round or oval hairless patch on the scalp.
      METHODS: Dermoscopic examination was performed for 148 patients with small round
      or oval hairless patch using DermLite(r) II pro. The type and its patient number
      of alopecia investigated in the study were as below: alopecia areata (n=81),
      trichotillomania (n=24), tinea captis (n=13), traction alopecia (n=12), lichen
      planopilaris (n=8), discoid lupus erythematosus (n=7), congenital triangular
      alopecia (n=2) and pseudopelade of Brocq (n=1). The significance of dermoscopic
      findings for each disease were evaluated. RESULTS: Characteristic dermoscopic
      findings of alopecia areata were tapering hairs and yellow dots. Those of
      trichotillomania and traction alopecia were broken hairs. Dermoscopic findings of
      tinea capitis included bent hairs, perifollicular white macules and greasy
      scales. Discoid lupus erythematosus and lichen planopilaris were characterized by
      dermoscopic findings of lack of follicular ostia. Furthermore, keratin plugs were
      frequently seen in discoid lupus erythematosus whereas perifollicular
      hyperkeratosis and erythema were frequently seen in lichen planopilaris.
      CONCLUSION: Dermoscopic examination for small round or oval hairless patch showed
      characteristic findings for each disease. Based on these results, we propose
      dermoscopic algorithm for small round or oval hairless patch on the scalp.

PMID- 24882978
TI  - Immunomodulatory effects of balneotherapy with hae-un-dae thermal water on
      imiquimod-induced psoriasis-like murine model.
AB  - BACKGROUND: Balneotherapy, although not a well-established dermatological
      treatment, is thought to have therapeutic properties for psoriasis and is used as
      an alternative treatment modality throughout the world. OBJECTIVE: To evaluate
      the mechanism underlying the therapeutic immunologic effects of thermomineral
      water. METHODS: A murine model of imiquimod-induced psoriasis-like skin
      inflammation was used for evaluating the therapeutic effects of balneotherapy
      with Hae-Un-Dae hot spring mineral water. The clinical improvements were
      evaluated by a dermatologist. Lesional cytokines, including interleukin (IL)-17A,
      IL-23, and IL-22, were quantitatively measured by real-time reverse transcriptase
      polymerase chain reaction. Serum levels of interferon-gamma, IL-4, IL-5, and IL
      17A were measured by enzyme-linked immunosorbent assay. T cell proportions in the
      spleen were evaluated by flow cytometry, and histopathological evaluation of the
      skin was also performed. RESULTS: The mineral water balneotherapy group showed
      faster improvement in skin erythema and scales than the distilled water bathing
      group. A substantial reduction was observed in the lesional mRNA levels of IL-17A
      and IL-23 in the mineral water group. Serum levels of IL-4 and IL-5 were
      significantly decreased in the mineral water group but not in the distilled water
      group. Normalized T cell proportions were observed after bathing. CONCLUSION:
      Balneotherapy showed immunomodulatory effects in a psoriasis-like murine model.
      Balneotherapy suppressed lesional IL-23 and IL-17A, which are important cytokines
      in the pathogenesis of psoriasis. These results suggest that balneotherapy can be
      used as an effective and safe treatment for psoriasis.

PMID- 24882979
TI  - A Recurrent Angiosarcoma Isolated to the Eyelid without the Recurrence on the
      Primary Lesion of the Forehead.
AB  - Angiosarcoma is a highly malignant vascular tumor of endothelial origin.
      Initially, a cutaneous manifestation presents as a singular or multifocal bruise
      like patches on the skin, most frequently on the face, the scalp or the neck
      regions. On progression, the lesions become violaceous, and ill-defined spongy
      nodular tumors appear. Our patient was a 71-year-old man with a previous history
      of angiosarcoma on the right forehead and was treated with an excision and local
      radiation 3 years ago. Several months after the treatment, a dark brownish to
      violaceous patch with edema arose from the right upper eyelid and spread out to
      the lower eyelid. Clinically, an ecchymosis caused by trauma or other hemangioma
      was suspected more than a recurrent angiosarcoma. Histopathologic examinations
      including immunohistochemical studies were consistent with cutaneous
      angiosarcoma. Herein, we report a rare case of a recurrent isolated angiosarcoma
      without the recurrence of a primary lesion. 

PMID- 24882980
TI  - Soft Tissue Infection Caused by Rapid Growing Mycobacterium following Medical
      Procedures: Two Case Reports and Literature Review.
AB  - Non-tubecrulosis mycobacterium infections were increasingly reported either
      pulmonary or extrapulmonary in the past decades. In Taiwan, we noticed several
      reports about the soft tissue infections caused by rapid growing mycobacterium
      such as Mycobacterium abscessus, Mycobacterium chelonae, on newspaper, magazines,
      or the multimedia. Most of them occurred after a plastic surgery, and medical or
      non-medical procedures. Here, we reported two cases of these infections following
      medical procedures. We also discussed common features and the clinical course of
      the disease, the characteristics of the infected site, and the treatment
      strategy. The literatures were also reviewed, and the necessity of the treatment
      guidelines was discussed. 

PMID- 24882981
TI  - Photodynamic Therapy for Bowen's Disease of the Vulva Area.
AB  - Bowen's disease is a squamous cell carcinoma in situ and has the potential to
      progress to a squamous cell carcinoma. The authors treated two female patients (a
      39-year-old and a 41-year-old) with Bowen's disease in the vulva area using
      topical photodynamic therapy (PDT), involving the use of 5-aminolaevulinic acid
      and a light-emitting diode device. The light was administered at an intensity of
      80 mW/cm(2) for a dose of 120 J/cm(2) biweekly for 6 cycles. The 39-year-old
      patient showed excellent clinical improvement, but the other patient achieved
      only a partial response. Even though one patient underwent a total excision 1
      year later due to recurrence, both patients were satisfied with the cosmetic
      outcomes of this therapy and the partial improvement over time. The common side
      effect of PDT was a stinging sensation. PDT provides a relatively effective and
      useful alternative treatment for Bowen's disease in the vulva area. 

PMID- 24882982
TI  - Acute generalized exanthematous pustulosis associated with tigecycline.
AB  - Acute generalized exanthematous pustulosis (AGEP) is a severe and rare eruption
      that develops mostly from factors related to drugs. It is characterized by a
      fever and a pustular eruption on the erythematous skin with an acute onset and
      without follicular localization. Etiopathogenesis has not yet been fully
      explained. Although it is similar to pustular psoriasis, its clinical, historical
      and histopathological characteristics are different. In this article, we present
      a case of AGEP associated with tigecycline that developed in a patient followed
      up in the intensive care unit for three months with an intra-abdominal injury
      after a trauma and Acinetobacter baumannii infection. 

PMID- 24882983
TI  - Solitary congenital erosion in a newborn: report of a solitary congenital self
      healing reticulohistiocytosis.
AB  - Congenital self-healing reticulohistiocytosis (CSHRH) is a rare, cutaneous, self
      limited form of Langerhans cell histiocytosis. Whereas multiple lesions are
      common, a solitary lesion is rare. A 14-day-old neonate presented with a
      solitary, 5-mm, oval, reddish, and eroded papule with crust on the left thigh
      that had existed since birth. No systemic involvement was found. Histopathology
      revealed dense infiltration of large histiocytes with scattered eosinophils and
      lymphocytes in the dermis. Immunohistochemistry showed S-100 and CD1a positivity.
      Two months later, the skin lesion involuted spontaneously, without evidence of
      recurrence and extracutaneous involvement. On the basis of the characteristic
      clinical course and typical histopathological findings, a diagnosis of solitary
      CSHRH was made. 

PMID- 24882984
TI  - Foreign body granuloma secondary to leuprorelin acetate.

PMID- 24882985
TI  - Expression of Cold-Inducible RNA-Binding Protein in Normal Skin, Actinic
      Keratosis and Squamous Cell Carcinoma.

PMID- 24882986
TI  - Pemphigus vulgaris in pregnancy associated with herpes virus type 1 infection.

PMID- 24882987
TI  - A rare case of annular pustular psoriasis associated with pemphigus foliaceus.

PMID- 24882988
TI  - Idiopathic acquired true leukonychia totalis and partialis.

PMID- 24882989
TI  - Piebaldism with neurofibromatosis type I: a familial case.

PMID- 24882990
TI  - Tinea incognito simulating herpes simplex virus infection.

PMID- 24882991
TI  - Allergic contact dermatitis caused by topical eye drops containing latanoprost.

PMID- 24882992
TI  - Pseudo-clubbing complicated by dermatophyte onychomycosis.

PMID- 24882993
TI  - Disseminated cryptococcosis with widespread necrotizing fasciitis and
      cryptococcemia occurring in an immunosuppressed patient.

PMID- 24882994
TI  - Levels of serum soluble p-selectin and e-selectin in psoriatic patients.

PMID- 24882995
TI  - Infantile perianal pyramidal protrusion.

PMID- 24882996
TI  - A Clinical Study of Nail Changes Occurring Secondary to Hand-Foot-Mouth Disease:
      Onychomadesis and Beau's Lines.

PMID- 24882997
TI  - Anetoderma developing in generalized granuloma annulare in an infant.

PMID- 24882998
TI  - 'Clues' for the histological diagnosis of tinea: how reliable are they?

PMID- 24882999
TI  - The Developmental Dynamics of Joining a Gang in Adolescence: Patterns and
      Predictors of Gang Membership.
AB  - Researchers have examined the predictors of adolescent gang membership, finding
      significant factors in the neighborhood, family, school, peers, and individual
      domains. However, little is known about whether risk and protective factors
      differ in predictive salience at different developmental periods. The present
      study examines predictors of joining a gang, tests whether these factors have
      different effects at different ages, and whether they differ by gender using the
      Seattle Social Development Project (SSDP) sample (n=808). By age 19, 173
      participants had joined a gang. Using survival analysis, results showed that
      unique predictors of gang membership onset included living with a gang member,
      antisocial neighborhood, and antisocial peer influences in the previous year. No
      time or gender interactions with predictors were statistically significant.

PMID- 24883001
TI  - Health Systems Are Capable of Handling a REMS.

PMID- 24883000
TI  - Gang Membership and Pathways to Maladaptive Parenting.
AB  - A limited amount of research examines the short-term consequences of gang
      membership. Rarer, though, is the examination of more distal consequences of gang
      membership. This is unfortunate because it understates the true detrimental
      effect of gang membership across the life course, as well as the effects it may
      have on children of former gang members. Using data from the Rochester Youth
      Development Study, this work investigates the impact of gang membership in
      adolescence (ages 12-18) on a particularly problematic style of parenting, child
      maltreatment. Using discrete time survival analysis, this study finds that gang
      membership increases the likelihood of child maltreatment and this relationship
      is mediated by the more proximal outcomes of gang membership during adolescence,
      precocious transitions to adulthood.

PMID- 24883002
TI  - That's the Way We Do Things Around Here!: Your Actions Speak Louder Than Words
      When It Comes To Patient Safety.
AB  - Actions on patient safety speak louder than words. 

PMID- 24883003
TI  - DEA Proposal on Hydrocodone Combination Products Divides Pharmacists: The Impacts
      on Pharmacy Workload and Prescription Drug Abuse Are at Issue.
AB  - DEA's hydrocodone combination plan divides pharmacists. 

PMID- 24883005
TI  - Pharmaceutical approval update.
AB  - Droxidopa (Northera) for neurogenic orthostatic hypotension, elosulfase alfa
      (Vimizim) for Morquio A syndrome, and sodium hyaluronate in phosphate-buffered
      saline (Monovisc) to address knee osteoarthritis. 

PMID- 24883006
TI  - Sofosbuvir: a new oral once-daily agent for the treatment of hepatitis C virus
      infection.
AB  - Sofosbuvir: A new oral oncedaily agent for the treatment of hepatitis C virus
      infection. 

PMID- 24883007
TI  - FDA devotes new resources to upgrading generic drug safety: but in some
      instances, the industry is pushing back.
AB  - The Food and Drug Administration, concerned about the quality of the generic
      drugs that represent 84 percent of U.S. prescriptions, is looking more closely at
      foreign manufacturing plants and weighing other changes in the generic approval
      process. 

PMID- 24883008
TI  - Mobile devices and apps for health care professionals: uses and benefits.
AB  - Health care professionals' use of mobile devices is transforming clinical
      practice. Numerous medical software applications can now help with tasks ranging
      from information and time management to clinical decision-making at the point of
      care. 

PMID- 24883009
TI  - After disappointments, Alzheimer's researchers seek out new paths: biomarkers and
      combination therapies may lead to disease-modifying treatments, experts say.
AB  - Developing a disease-modifying treatment for Alzheimer's disease has stymied
      researchers. A collaborative re-examination of premises that guided disappointing
      earlier trials is under way, with talk of new targets and combination therapies. 

PMID- 24883010
TI  - American academy of dermatology and american college of cardiology.
AB  - Attendees at the American Academy of Dermatology meeting found heightened
      interest in psoriasis treatments. The American College of Cardiology meeting
      included sessions on heparin versus bivalirudin and a controversy over renal
      denervation. 

PMID- 24883011
TI  - Dyadic Curve-of-Factors Model: An Introduction and Illustration of a Model for
      Longitudinal Non-Exchangeable Dyadic Data.
AB  - The analysis of longitudinal data collected from non-exchangeable dyads presents
      a challenge for applied researchers for various reasons. This paper introduces
      the Dyadic Curve-of-Factors Model (D-COFM) which extends the Curve-of-Factors
      Model (COFM) proposed by McArdle (1988) for use with non-exchangeable dyadic
      data. The D-COFM overcomes problems with modeling composite scores across time
      and instead permits examination of the growth in latent constructs over time. The
      D-COFM also appropriately models the interdependency among non-exchangeable
      dyads. Different parameterizations of the D-COFM are illustrated and discussed
      using a real dataset to aid applied researchers when analyzing dyadic
      longitudinal data.

PMID- 24883013
TI  - Regeneration of corneal endothelial cells following keratoplasty in rats with
      bullous keratopathy.
AB  - PURPOSE: Little is known about the behavior of the endothelial cell (EC) layer
      following keratoplasty. In vitro experiments suggested that the peripheral
      endothelium might have a higher regenerative capacity than the central
      endothelium, and some authors hypothesized that endothelial progenitor cells are
      present in the limbal area. Thus, we analyzed the corneal endothelial
      regenerative capacity in vivo in a rat model of bullous keratopathy using either
      bullous central grafts or bullous peripheral recipient corneas to analyze
      differences in EC regeneration depending on central versus peripheral cell
      origin. METHODS: Bullous keratopathy was induced in Lewis rats with an
      intracameral injection of benzalkonium chloride (0.05%; BAK). Three days later,
      the central area of the bullous cornea was excised and used as a bullous graft,
      transplanted to a healthy, green fluorescent protein (GFP)-transgeneic Lewis
      receipient rat (group 'bullous graft'). In return, the mentioned rat eye with the
      bullous keratopathy received a healthy GFP-transgeneic corneal transplant (group
      'bullous host'). A subgroup of these animals received a healthy, excentrically
      trephined including parts of the limbus (group 'bullous host, limbo
      keratoplasty'). The grafts were monitored clinically for 7 weeks. Subsequently,
      the mean EC density was calculated on corneal whole mounts with Alizarin Red S
      staining. GFP was analyzed with confocal microscopy to determine EC origin.
      Untreated fellow eyes served as controls. RESULTS: BAK injection led to a
      significant decrease in the mean EC density with subsequent bullous keratopathy.
      In the control eyes, the mean EC density was 3,744 cells/mm2 in the center and
      2,811 cells/mm2 in the periphery. In eyes with bullous keratopathy, only 233
      cells/mm2 in the center and 622 cells/mm2 in the periphery were observed three
      days after BAK-injection. Bullous transplants in the group 'bullous graft'
      cleared, and GFP-positive cells were detected on the transplant. In contrast, no
      GFP-positive ECs were detected on the host cornea in the groups 'bullous host'.
      CONCLUSIONS: ECs from the peripheral cornea have the ability to cross the graft
      border and compensate for the pathologically altered/absent endothelium on the
      graft. In contrast, ECs derived from the central cornea remain central on the
      graft and do not replace or regenerate peripheral ECs in our model of bullous
      keratopathy.

PMID- 24883012
TI  - Gap junction proteins in the light-damaged albino rat.
AB  - PURPOSE: Changes in connexin expression are associated with many pathological
      conditions seen in animal models and in humans. We hypothesized that gap
      junctions are important mediators in tissue dysfunction and injury processes in
      the retina, and therefore, we investigated the pattern of connexin protein
      expression in the light-damaged albino rat eye. METHODS: Adult Sprague-Dawley
      rats were exposed to intense light for 24 h. The animals were euthanized, and
      ocular tissue was harvested at 0 h, 6 h, 24 h, 48 h, and 7 days after light
      damage. The tissues were processed for immunohistochemistry and western blotting
      to analyze the expression of the gap junction proteins in the light-damaged
      condition compared to the non-light-damaged condition. Cell death was detected
      using the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling
      (TUNEL) technique. RESULTS: Intense light exposure caused increased TUNEL
      labeling of photoreceptor cells. Immunocytochemistry revealed that connexin 36
      (Cx36) was significantly increased in the inner plexiform layer and Cx45 was
      significantly decreased in the light-damaged retina. The pattern of Cx36 and Cx45
      labeling returned to normal 7 days after light damage. Cx43 significantly
      increased in the RPE and the choroid in the light-damaged tissue, and decreased
      but not significantly in the retina. This elevated Cx43 expression in the choroid
      colocalized with markers of nitration-related oxidative stress (nitrotyrosine)
      and inflammation (CD45 and ionized calcium-binding adaptor molecule-1) in the
      choroid. CONCLUSIONS: The results suggest that connexins are regulated
      differently in the retina than in the choroid in response to photoreceptor
      damage. Changes in connexins, including Cx36, Cx43, and Cx45, may contribute to
      the damage process. Specifically, Cx43 was associated with inflammatory damage.
      Therefore, connexins may be candidate targets for treatment for ameliorating
      disease progression.

PMID- 24883014
TI  - First report of OPA1 screening in Greek patients with autosomal dominant optic
      atrophy and identification of a previously undescribed OPA1 mutation.
AB  - PURPOSE: To describe the genotype-phenotype correlation in four Greek pedigrees
      with autosomal dominant optic atrophy (ADOA) and OPA1 mutations. METHODS: Seven
      patients from four unrelated families (F1, F2, F3, F4) were clinically assessed
      for visual acuity, color vision, ptosis, afferent pupillary defects, and visual
      fields and underwent orthoptic assessment, slit-lamp biomicroscopy, and fundus
      examination to establish their clinical status. Genomic DNA was extracted from
      peripheral blood samples from all participants. The coding region (exons 1-28),
      including the intron-exon boundaries of the OPA1 gene, was screened in the
      probands of the four families, as well as in seven additional family members
      (four affected and three unaffected) with PCR and direct DNA sequencing. RESULTS:
      All patients presented bilateral decrease in best-corrected visual acuity and
      temporal pallor of the optic disc. The visual fields of the adult patients showed
      characteristic scotomata. Other signs were present in some patients such as
      decreased color discrimination and a gray crescent within the neuroretinal rim.
      After the OPA1 gene was sequenced, a previously undescribed heterozygous splice
      site mutation c.784-1G>T in intron 7 was detected in family F2. In families F1,
      F3, and F4, a previously reported in-frame deletion
      c.876_878delTGT/p.(Val294del), the frameshift c.2366delA/p.(Asn789Metfs*11), and
      splice-site c.1140+5G>C mutations were detected, respectively. CONCLUSIONS: This
      is the first report of molecular characterization of Greek patients with ADOA.
      Our findings provide additional information regarding the genotype-phenotype
      correlation and establish the role of the OPA1 gene in Greek patients with ADOA.

PMID- 24883015
TI  - Toll-like receptor 4 polymorphisms and their haplotypes modulate the risk of
      developing diabetic retinopathy in type 2 diabetes patients.
AB  - PURPOSE: Persistent inflammation and impaired neovascularization in type 2
      diabetes mellitus (T2DM) patients may lead to development of macro- and
      microvascular complications. Diabetic retinopathy (DR) is one of the secondary
      microvascular complications of T2DM. Improper activation of the innate immune
      system may be an important contributor in the pathophysiology of DR. Toll-like
      receptor 4 (TLR4) is an important mediator of innate immunity, and genetic
      alterations in TLR4 support inflammation in the hyperglycemic condition. The
      present work was designed to investigate whether the TLR4 single nucleotide
      polymorphisms (SNPs) rs4986790, rs4986791, rs10759931, rs1927911, and rs1927914
      are associated with DR in a north Indian population. METHODS: The study group of
      698 individuals (128 DR, 250 T2DM, 320 controls) was genotyped by PCR-RFLP.
      Haplotype and linkage disequilibrium between SNPs were determined using Haploview
      software. RESULTS: Combined risk genotypes of TLR4 SNPs rs10759931 (odds ratio
      [OR] 1.50, p = 0.05) and rs1927914 (OR 1.48, p = 0.05) were found to be
      significantly associated with pathogenesis of DR. A total of 14 haplotypes with
      frequency >1% were obtained using Haploview software. Haplotypes ACATC (37.5%)
      and ACATT (14.8%) were the two most common haplotypes obtained. CONCLUSIONS:
      Results of the present case-control study that included 698 north Indian subjects
      suggested that TLR4 SNPs rs10759931 and rs1927914 modulate the risk of DR in T2DM
      cases. Association analysis using haplotypes showed none of the haplotypes were
      associated with either susceptibility or resistance to DR in a north Indian
      population.

PMID- 24883016
TI  - Identification of MYOC gene mutation and polymorphism in a large Malay family
      with juvenile-onset open angle glaucoma.
AB  - PURPOSE: To screen for mutations in the coding region of the myocilin (MYOC) gene
      in a large Malay family with juvenile-onset open angle glaucoma (JOAG). METHODS:
      A total of 122 family members were thoroughly examined and screened for JOAG.
      Venipuncture was conducted. Genomic DNA was extracted from peripheral blood
      leukocytes. The presence of a mutation and a polymorphism was ascertained with
      PCR amplification followed by the direct sequencing technique. RESULTS: Thirty
      two of the 122 screened family members were identified to have JOAG (11 new cases
      and 21 known cases). An autosomal dominant inheritance pattern with incomplete
      penetrance was observed. A C->A substitution at position 1440 in exon 3 that
      changes asparagine (AAC) to lysine (AAA) was identified in affected family
      members except two probands (III:5 and IV:6). Six probands were identified as
      having the Asn480Lys mutation but have not developed the disease yet. An intronic
      polymorphism IVS2 730 +35 G>A was also identified. There was a significant
      association between Asn480Lys (p<0.001) and IVS2 730+35G>A (p<0.001) in the
      affected and unaffected probands in this family. CONCLUSIONS: The Asn480Lys
      mutation and the IVS2 730+35 G>A polymorphism increased susceptibility to JOAG in
      this large Malay pedigree. Identifying the MYOC mutations and polymorphisms is
      important for providing presymptomatic molecular diagnosis.

PMID- 24883017
TI  - Lectin-carbohydrate interactions on nanoporous gold monoliths.
AB  - Monoliths of nanoporous gold (np-Au) were modified with self-assembled monolayers
      of octadecanethiol (C18-SH), 8-mercaptooctyl alpha-D-mannopyranoside (alphaMan-C8
      SH), and 8-mercapto-3,6-dioxaoctanol (HO-PEG2-SH), and the loading was assessed
      using thermogravimetric analysis (TGA). Modification with mixed SAMs containing
      alphaMan-C8-SH (at a 0.20 mole fraction in the SAM forming solution) with either
      octanethiol or HO-PEG2-SH was also investigated. The np-Au monoliths modified
      with alphaMan-C8-SH bind the lectin Concanavalin A (Con A), and the additional
      mass due to bound protein was assessed using TGA analysis. A comparison of TGA
      traces measured before and after exposure of HO-PEG2-SH modified np-Au to Con A
      showed that the non-specific binding of Con A was minimal. In contrast, np-Au
      modified with octanethiol showed a significant mass loss due to non-specifically
      adsorbed Con A. A significant mass loss was also attributed to binding of Con A
      to bare np-Au monoliths. TGA revealed a mass loss due to the binding of Con A to
      np-Au monoliths modified with pure alphaMan-C8-SH. The use of mass losses
      determined by TGA to compare the binding of Con A to np-Au monoliths modified by
      mixed SAMs of alphaMan-C8-SH and either octanethiol or HO-PEG2-SH revealed that
      binding to mixed SAM modified surfaces is specific for the mixed SAMs with HO
      PEG2-SH but shows a significant contribution from non-specific adsorption for the
      mixed SAMs with octanethiol. Minimal adsorption of immunoglobulin G (IgG) and
      peanut agglutinin (PNA) towards the mannoside modified np-Au monoliths was
      demonstrated. A greater mass loss was found for Con A bound onto the monolith
      than for either IgG or PNA, signifying that the mannose presenting SAMs in np-Au
      retain selectivity for Con A. TGA data also provide evidence that Con A bound to
      the alphaMan-C8-SH modified np-Au can be eluted by flowing a solution of methyl
      alpha-D-mannopyranoside through the structure. The presence of Con A proteins on
      the modified np-Au surface was also confirmed using atomic force microscopy
      (AFM). The results highlight the potential for application of carbohydrate
      modified np-Au monoliths to glycoscience and glycotechnology and demonstrate that
      they can be used for capture and release of carbohydrate binding proteins in
      significant quantities.

PMID- 24883019
TI  - Atomic force microscopy of bacteria from periodontal subgingival biofilm:
      Preliminary study results.
AB  - OBJECTIVE: Atomic force microscope (AFM) is a technology that allows analysis of
      the nanoscale morphology of bacteria within biofilm and provides details that may
      be better useful for understanding the role of bacterial interactions in the
      periodontal disease. MATERIAL AND METHODS: Five patients with periodontal >=5 mm
      pockets diagnosed as generalized periodontitis and five patients with slight
      gingivitis were selected for the investigation. Bacteria biofilms were collected
      and morphologically investigated by AFM application. RESULTS: The investigation
      revealed how periodontitis bacteria are characterized by specific morphologic
      features of the cell wall. The major representative species of bacteria causing
      periodontal diseases have been reproduced by a three-dimensional reconstruction
      showing the bacteria surface details. CONCLUSIONS: The presence of complex
      glycocalyx structures, bacteriophage-like vesicles, spirochetes (classic and
      cystic morphology) and bacterial co-aggregation has been identified by the AFM
      analysis. The results suggest that AFM is a reliable technique for studying
      bacterial morphology and for examining microbial interactions in dental plaque.

PMID- 24883018
TI  - Acute administration of methylphenidate alters the prefrontal cortex neuronal
      activity in a dose-response characteristic.
AB  - The prefrontal cortex (PFC) is part of the collective structures known as the
      motive circuit. The PFC acts to enhance higher cognitive functions as well as
      mediate the effects of psychostimulants. Previous literature shows the importance
      of PFC neuronal adaptation in response to acute and chronic psychostimulant
      exposure. The PFC receives input from other motive circuit structures, including
      the ventral tegmental area, which mediates and facilitates the rewarding effects
      of psychostimulant exposure. PFC neuronal and locomotor activity from freely
      behaving rats previously implanted with permanent semimicroelectrodes were
      recorded concomitantly using a telemetric (wireless) recording system.
      Methylphenidate (MPD) is used as a leading treatment for behavioral disorders and
      more recently as a cognitive enhancer. Therefore, the property of MPD dose
      response on PFC neuronal activity was investigated. The results indicate that MPD
      modulates PFC neuronal activity and behavioral activity in a dose-dependent
      manner. PFC neuronal responses to 0.6 mg/kg elicited mainly a decrease in PFC
      neuronal activity, while higher MPD doses (2.5 and 10.0 mg/kg) elicited mainly
      increased neuronal activity in response to MPD. The correlation between MPD
      effects on PFC neuronal activity and animal behavior is discussed.

PMID- 24883020
TI  - Reliability analysis of two methods for measuring active enamel demineralization:
      An in vitro study.
AB  - OBJECTIVE: The aim was to evaluate the intra- and inter-examiner reliability of
      two methods, namely, digital caliper [DC] and computerized image analysis
      software (Image Tool [IT] version 4.1) for measuring the area of an active enamel
      demineralization lesion. The effect on that measurement of a window that delimits
      the lesion was also assessed. MATERIALS AND METHODS: Thirty-eight circular
      artificial enamel demineralization lesions (r = 2 mm) were produced on bovine
      teeth in vitro, which were then measured three times by three examiners, with and
      without the presence of a window delimiting the area to be measured. The data
      were analyzed by the intraclass correlation coefficient (ICC) with 95% confidence
      interval (CI) and by the Altman and Bland analysis. RESULTS: The intra-examiner
      correlation using the IT method showed excellent reproducibility (mean ICC values
      0.922-0.970 with the delimiting window and 0.915-0.990 without the window).
      However, the intra-examiner correlation using the DC method showed comparatively
      less reproducibility in the measurements (mean ICC values 0.458-0.648 with the
      delimiting window and 0.378-0.665 without the window). The inter-examiner
      correlations showed very good reproducibility of the measurements regardless of
      the presence or absence of the window for both the DC method (0.811-0.846) and IT
      method (0.953-0.994). However, the latter method showed less variability within
      the measurements. CONCLUSION: However, statistically no significant difference
      was found between both methodologies. Nevertheless, computerized image analysis
      with the Image Tool software demonstrated higher intra- and inter-examiner
      reliability than the digital caliper method, in estimating the area of the enamel
      demineralization lesion, regardless of the delimiting window.

PMID- 24883022
TI  - Spectrophotometric evaluation of the color changes of different feldspathic
      porcelains after exposure to commonly consumed beverages.
AB  - OBJECTIVE: The aim of this study was to compare color stability and surface
      topography of three different feldspathic porcelains both qualitatively and
      quantitatively after exposure to routinely consumed beverages over different time
      periods using a Spectrophotometer, Stereomicroscope and Surface roughness tester,
      respectively. MATERIALS AND METHODS: A total of 90 plastic discs were casted to
      obtain metal dies for three different newer ceramic applications each on thirty
      samples. The color and surface roughness of these samples were measured using
      stereomicroscope and surface roughness tester following which they were kept in
      different test solutions for different durations and revaluated for color changes
      and surface roughness in the similar manner. RESULTS AND CONCLUSION: Among all
      the five test solutions, Coffee showed the maximum staining of the ceramic
      whereas maximum surface roughness was shown by the Duceram Kiss (1.48 MUm) by
      Orange Juice which could be due to its high titratable acidity.

PMID- 24883021
TI  - Does the temperature of beverages affect the surface roughness, hardness, and
      color stability of a composite resin?
AB  - OBJECTIVE: To investigate the effect of beverages' temperature on the surface
      roughness, hardness, and color stability of a composite resin. MATERIALS AND
      METHODS: Fifty specimens of the Filtek Z250 composite (3M ESPE, Dental Products,
      St.Paul, MN, USA) were prepared and initial roughness, microhardness, and color
      were measured. Then the specimens were randomly divided into five groups of 10
      specimens each: Coffee at 70 degrees C, coffee at 37 degrees C, cola at 10
      degrees C, cola at 37 degrees C, and artificial saliva (control). After the
      samples were subjected to 15 min * 3 cycles per day of exposure to the solutions
      for 30 days, the final measurements were recorded. RESULTS: After immersion in
      beverages, the artificial saliva group showed hardness values higher than those
      of the other groups (P < 0.001) and the microhardness values were significantly
      different from the initial values in all groups except for the control group.
      Both cola groups showed roughness values higher than the baseline values (P <
      0.05), while the other groups showed values similar to the baseline measurements.
      When DeltaE measurements were examined, the 70 degrees C coffee group showed the
      highest color change among all the groups (P < 0.05). CONCLUSION: High
      temperature solutions caused alterations in certain properties of composites,
      such as increased color change, although they did not affect the hardness or
      roughness of the composite resin material tested.

PMID- 24883023
TI  - Dental subscale of children's fear survey schedule and dental caries prevalence.
AB  - OBJECTIVE: To assess the level of fear of dental procedures among 6-12 year
      school children and correlate the prevalence of dental caries with their dental
      fears scores. MATERIALS AND METHODS: The study sample of 444 school children,
      comprising of 224 girls and 220 boys in the age group of 6-12 years old from a
      private English medium school were selected. Each student was asked to
      independently complete a Children's Fear Survey Schedule - Dental Subscale (CFSS
      DS) questionnaire. Children having a score of >= 38 were included in the "dental
      fear" group while those scoring <38 were placed in the "without dental fear"
      group. All dental examinations were performed in the classroom. RESULTS: Fear
      scores were highest for "Injections," (3.76 +/- 0.68) "Choking," (3.48 +/- 0.63)
      and "Dentist drilling" (2.88 +/- 0.69). The overall mean score of CFSS-DS in our
      study was 37.0 +/- 8.89, mean score of DMFT and DMFS were 0.58 +/- 0.74 and 0.73
      +/- 1.09, respectively. Mean score of deft and defs were 4.40 +/- 2.34 and 7.28
      +/- 5.49, respectively. CONCLUSION: The study showed the prevalence of dental
      fear in 6-12 year old children and there was no statistically significant co
      relation between the level of dental fear and dental caries in these children.

PMID- 24883024
TI  - Evaluation of two different root-end cavity preparation techniques: A scanning
      electron microscope study.
AB  - OBJECTIVE: In this study, we aimed to evaluate and compare the dentinal walls of
      root-end cavities for the presence of cracks after cavity preparation using US
      retrotips and Er: YAG laser. MATERIALS AND METHODS: Fifty single-rooted teeth
      were prepared by Protaper NiTi rotary system and obturated by lateral
      condensation. Three milimeters of root-end was resected. Twenty teeth were
      prepared with US retrotip (Group 1), 20 teeth with Er: YAG laser (Group 2), and
      10 teeth without retropreparation (control group). The root-end surfaces were
      examined under a scanning electron microscope (SEM). Then the cracks of the
      resected root surfaces were evaluated on microphotographs. RESULTS: No
      statistically significant difference was detected between US Group and Laser
      Group for complete, incomplete, intradentinal, and total number of cracks (P =
      0.47, P = 0.80, P = 0.69, P = 0.869, respectively). CONCLUSION: Statistical
      analysis revealed no significant effect of retropreparation technique on the
      development of apical cracks (P > 0.05).

PMID- 24883025
TI  - Correlation between the salivary Streptococcus mutans levels and dental caries
      experience in adult population of Chandigarh, India.
AB  - OBJECTIVES: To determine the level of Streptococcus mutans (S. mutans) in adults
      of Chandigarh and to correlate the dental caries in these individuals with their
      S. mutans titers. MATERIALS AND METHODS: Salivary levels of Streptococcus mutans,
      using Dentocult SM commercial kits were estimated in 200, 25-35 year old adults
      (males and females). Streptococcus mutans were detected in 87% of the study
      sample. Score 2, representing 10(5)-10(6) CFU/ml (Colony Forming Unit) of saliva
      was found to be most prevalent, i.e. in 80 of 200 adults, followed by score 1,
      depicting S mutans with <10(5) CFU/ml, in 56 of 200 adults and score 3, with
      bacterial titer >10(6) CFU/ml in 38 of 200 adults. RESULTS: Dental caries,
      recorded using Moller's index, was found to be maximum in individuals with score
      3, followed by score 2,1 and 0, thereby showing a positive correlation of dental
      caries with increasing titers of S. mutans. This correlation was statistically
      highly significant in males with figures as 8.73 decayed surfaces at score 2
      rising to 17.38 at score 3. The mean of DMFT was higher among females than in the
      males in the present study. CONCLUSION: The split up data in males and females,
      showed a positive association between caries experience and salivary S. mutans
      scores. The results of the study will serve as a baseline data for future
      planning of preventive programs in adults.

PMID- 24883026
TI  - Fluoride release of glass ionomer restorations after bleaching with two different
      bleaching materials.
AB  - OBJECTIVE: This study was designed to evaluate the effect of two bleaching agents
      on the fluoride release of three types of glass ionomer materials. MATERIALS AND
      METHODS: A total of 90 specimens of the tested materials (Ketac Fil, Photac Fil
      and F2000) were prepared by a split Teflon ring with an internal diameter of 5 mm
      and thickness of 2 mm. The tested materials were applied and bleached according
      to manufacturer instructions. Fluoride release measurements were made by using
      specific ion electrode. RESULTS: Results revealed that bleaching with opalescence
      Xtra caused little increase in fluoride release from Ketac Fil and Photac Fil but
      has no effect on F2000. However, Opalescence Quick had no significant effect on
      the three tested materials. CONCLUSIONS: Bleaching effect on fluoride release is
      material dependent and time has a significant role on fluoride release.

PMID- 24883027
TI  - Chemical composition and thermal behavior of five brands of thermoplasticized
      gutta-percha.
AB  - OBJECTIVE: The aim of this study was determine the chemical composition and
      thermal behavior of Thermafil (TH), Microseal Cone (MC), Microseal Microflow
      (MF), Obtura (OB) and Obtura Flow (OF). In addition, their thermal behavior in
      response to temperature variations was studied by differential scanning
      calorimetry (DSC) to determine the temperature at which gutta-percha switches
      from the beta to alpha form, and from the alpha to the amorphous phase. MATERIALS
      AND METHODS: The organic and inorganic fractions were separated by dissolution in
      chloroform. Gutta-percha (GP) was precipitated with acetone. The inorganic
      fraction was analyzed via Elemental Microanalysis. Energy Dispersive X-ray
      Microanalysis and X-ray Diffraction were used to identify the chemical elements
      and compounds (BaSO4 and ZnO). Thermal analysis was conducted using DSC. RESULTS:
      The organic and inorganic fractions ranged from 21.3% and 26.9% of weights,
      respectively. MC and MF showed the highest percentages of organic compounds (P =
      0.0125). All specimens exhibited two crystalline transformations when heated from
      ambient temperature to 130 degrees C. MC presented the highest percentage of GP.
      CONCLUSIONS: No correlation was observed between chemical composition and thermal
      behavior. Each of the products showed thermal behavior that is typical of beta
      phase gutta-percha.

PMID- 24883028
TI  - Is the 810-nm diode laser the best choice in oral soft tissue therapy?
AB  - OBJECTIVE: To evaluate the safety and efficacy of an 810-nm diode laser for
      treatment of benign oral soft tissue lesions. MATERIALS AND METHODS: Treatment
      with the 810-nm diode laser was applied to a group of eighteen patients with
      pathological frenulum and epulis fissuratum; five patients with oral lichen
      planus, oral leukoplakia, and mucous membrane pemphigoid; and four patients with
      pyogenic granuloma. RESULTS: Although the conventional surgery wound heals in a
      fairly short time, in the present study, the simple oral soft tissue lesions
      healed within two weeks, the white and vesiculobullous lesions healed completely
      within six weeks, and the pyogenic granuloma lesions healed within four weeks.
      Any complication was treated by using the 810-nm diode laser. CONCLUSIONS:
      Patient acceptance and satisfaction, without compromising health and function,
      have been found to be of a high degree in this present study. Thus, we can say
      that the use of the 810-nm diode laser may indeed be the best choice in oral soft
      tissue surgery.

PMID- 24883029
TI  - Qualitative and quantitative assessment of relationship between mandibular third
      molar and angle fracture on North Indian population: A clinico-radiographic
      study.
AB  - OBJECTIVE: To assess the relationship between impacted mandibular third molar
      presence and the risk for mandibular angle fracture with the effect of various
      positions of mandibular third molar and the risk of mandibular angle fracture.
      MATERIALS AND METHODS: In the North Indian territory, a total of 289 patients
      with mandibular angle fractures were studied and evaluated for the possible
      relationship with impacted third molar on the basis of clinical and panoramic
      radiographical findings. RESULTS: Results that confirmed the highest risk for
      mandibular angle fracture was associated with mesioangular angulations (45.42%)
      followed by vertical (26.34%), distoangular in sequence and least risk was found
      with bucco-version angulations (2.67%) according to Winter's classification.
      Additionally, the highest risk of mandibular angle fracture was reported with
      partially erupted third molar (47.75%), followed by erupted (23.53%) and
      unerupted third molar (19.38%). CONCLUSION: The risk for mandibular angle
      fracture is not only affected by status of eruption, angulations, position,
      number of roots present in third molar but also by the distance of mandibular
      third molar from inferior border of mandible and the percentage of remaining
      amount of bone at the mandibular angle region.

PMID- 24883030
TI  - Evaluation of dental students' perception and self-confidence levels regarding
      endodontic treatment.
AB  - OBJECTIVES: The aim of this study was to obtain information about senior dental
      students' perceptions and self-confidence levels regarding endodontic practice.
      MATERIALS AND METHODS: Anonymous survey forms were handed out to senior students
      at Yeditepe University, Faculty of Dentistry. The students were asked to score
      their level of confidence using a 5-point scale and comment about future
      practices. RESULTS: The response rate of the survey was 88%. 11.9% expressed
      endodontics as the first branch in terms of difficulty. The majority (90.5%)
      indicated they would perform root canal treatments within their expertise limit
      in the future but refer difficult cases to an endodontist. Bleaching of
      endodontically treated teeth, managing flare-ups, placement of a rubber dam were
      procedures in which students reported the lowest confidence (2.55 +/- 1.17, 3.24
      +/- 0.96, 3.24 +/- 1.19, respectively). On the other hand, students felt the
      lowest confidence in the treatment of maxillary molars followed by mandibular
      molars (3.43 +/- 1.02 and 3.93 +/- 0.97, respectively). Students also reported
      the lowest confidence in root resorptions, endo-perio lesions, traumas,
      retreatments and apexifications (2.93 +/- 1.16, 3.07 +/- 0.89, 3.24 +/- 0.85,
      3.33 +/- 1.7 and 3.36 +/- 1.1, respectively). CONCLUSIONS: The results showing
      students' lower confidence in more challenging aspects of dentistry may be
      related with the attitude of dental schools to refer these cases to post graduate
      students and instilling information about these cases on a theoretical basis
      only. Though there seems to be a tendency for students to refer challenging cases
      to a specialist in future, authorities should give priority to enhance the way
      information and experience is conveyed regarding various aspects of endodontic
      treatment.

PMID- 24883031
TI  - A case of accidental aspiration of an endodontic instrument by a child treated
      under conscious sedation.
AB  - Dental management of children with attention-deficit hyperactivity disorder
      (ADHD) often requires the need for pharmacological behavior management techniques
      such as the use of sedation. The purpose of this article is to describe a
      clinical case involving accidental aspiration of an Endodontic instrument during
      root canal therapy under sedation. To our knowledge, this is the first case
      report of aspiration of an Endodontic instrument and should serve to heighten the
      awareness with regard to aspiration during dental procedures under sedation. It
      also emphasizes the need for proper isolation techniques in patients treated
      under sedation, thereby preventing such complications. 

PMID- 24883032
TI  - Replantation after traumatic avulsion.
AB  - The aim of this report is to present the case of an accidentally avulsed
      maxillary central incisor kept in saline solution from the moment of trauma until
      its replantation 3 h later in a 13-year-old girl. The avulsed tooth was replanted
      back into the alveolar socket and splinted with composite resin. Calcium
      hydroxide intracanal dressing was used to prevent inflammatory root resorption.
      Radiographic and clinical examinations were performed during 27 months follow-up.
      During the 15 months follow-up period, the tooth remained in a stable functional
      position and did not reveal replacement resorption. But mild infraocclusion and
      root resorption were developed 21 months after replantation. The amount of damage
      to tooth and supporting structures, emergency treatment and follow-up period play
      a role in the prognosis of the avulsed tooth. It can be recommended to keep the
      avulsed tooth in saline solution at least when more appropriate storage media are
      not on handle immediately. 

PMID- 24883033
TI  - Addition of a pontic to all-ceramic Turkom-Cera fixed partial denture
      restorations.
AB  - High-strength all-ceramic materials are commonly used in dentistry. When
      complications occur in an all-ceramic restoration, the restoration is usually
      replaced. This article describes the time-saving ability and cost-effectiveness
      of this novel technique for the addition of a pontic in two complicated clinical
      cases. Turkom-Cera(TM) [Turkom-Ceramic (M) Sdn. Bhd.] with aluminum oxide
      (99.98%) is an all-ceramic system that offers the option of addition of a new
      pontic to the sintered framework. The new pontic was cut off from an alumina
      blank [Turkom-Ceramic (M) Sdn. Bhd.], moistened, and attached to the framework
      using alumina gel [Turkom-Ceramic (M) Sdn. Bhd.]. The framework was veneered with
      veneering porcelain (Vita VM 7; VITA Zahnfabrik). The two cases presented here
      involving the addition of a pontic to sintered framework were followed up for at
      least 1 year. No complication was detected or reported by the patients. Alumina-
      and zirconia-based ceramics are particularly suitable for for all-ceramic
      restorations in high-stress bearing areas. However, replacement of a failed all
      ceramic restoration is not the most practical solution, considering both cost and
      tooth-related factors. This attractive feature of the Turkom-Cera allows the
      repair of a fractured ceramic coping or the addition of a new pontic to
      restorations. 

PMID- 24883034
TI  - Fused primary first mandibular macromolar with a unique relation to its permanent
      successors: A rare tooth anomaly.
AB  - Dental anomalies of number and forms may occur in the primary and permanent
      dentition. Various terms have been used to describe dental twinning anomalies:
      Germination, fusion, concrescence, double teeth, conjoined teeth, twinned teeth,
      geminifusion, and vicinifusion. Fused tooth is a developmental anomaly that is
      seen more frequently in the primary than the permanent dentition. Double tooth
      involving deciduous anterior teeth is found mostly in the mandible. Very few
      cases of nonsyndromic double primary molar have been reported in the literature.
      The succeeding permanent tooth is often found missing congenitally in the same
      region. This article reports a very rare unilateral occurrence of an anomalous,
      primary mandibular first macromolar formed by fusion with a dysmorphic premolar
      like supernumerary tooth in deciduous dentition period. Instead of agenesis of
      succedaneous tooth, the double tooth has been succeeded by normally developing
      mandibular first premolar in the same region. 

PMID- 24883035
TI  - Multiple oral ulcers leading to diagnosis of pulmonary tuberculosis.
AB  - We report a 47 year old man who presented with painful non-healing tongue ulcers
      of 3 months duration. Examination revealed an additional buccal ulcer that he was
      unaware of. Histopathology of the ulcers showed caseation necrosis. Following
      this report, chest radiography and sputum microscopy performed revealed pulmonary
      tuberculosis. From this case-study, one should be aware of coexisting pulmonary
      tuberculosis in patients with chronic non-healing oral ulcers, both for diagnosis
      as well as prevention of transmission through respiratory droplets. 

PMID- 24883036
TI  - Chemoprevention of premalignant and malignant lesions of oral cavity: Recent
      trends.
AB  - The word chemoprevention includes prevention of initiation, promotion, and
      progression of carcinogenesis to cancer. This article is an attempt to review the
      dietary chemopreventive agents and their mode of action in chemoprevention of
      oral premalignant lesions and oral cancer using a systematic approach. Selected
      chemoprevention trials are discussed with a focus on strategies of trial design
      and clinical outcome. Future in the field of chemoprevention will be more
      promising than the recently available therapeutic alternatives. 

PMID- 24883037
TI  - Reappraisal of the removable partial denture as a treatment option for the
      shortened dental arch.
AB  - For patients with shortened dental arches, many treatment options are available.
      The existing situation can be maintained by stabilizing the present dentition and
      improving the occlusion without extending the arch. Alternatively, the shortened
      dental arch can be extended by either a free-end saddle removable partial
      denture, cantilevered fixed bridge, or by an implant-supported prosthesis. The
      free-end saddle removable partial denture can be considered a simple, non
      invasive, and relatively cheap treatment option for the shortened dental arch. It
      was believed that such prosthodontic rehabilitation would be beneficial for the
      patients in terms of improving oral functions. However, the existing literature
      indicates that the prognosis of free-end saddle removable partial denture is not
      predictable, it is problematic, and its contribution to oral functions in
      patients with shortened dental arches is considered to be dubious. This paper
      reviews and summarizes the current literature about the outcome of extending the
      shortened dental arch by a free-end saddle removable partial denture. It also
      outlines factors that may affect the prognosis of this prosthetic treatment. 

PMID- 24883039
TI  - Caries prevention: A global strategy.

PMID- 24883038
TI  - Dentoalveolar surgery techniques combined with orthodontic treatment: A
      literature review.
AB  - Surgery on the dentoalveolar process combined with orthodontic treatment was
      emphasized as an alternative method for reducing the treatment time and improving
      the orthodontic treatment on post-adolescent and adult patients. This combined
      treatment facilitates and accelerates orthodontic tooth movement. This article
      reviews the clinical practice in surgery-assisted orthodontic treatment in
      relation to historical perspective, indications and biological principles, as
      well as limitations and risks of dento-osseous surgical techniques, including
      dento-osseous osteotomy and/or ostectomy, dento-osseous microfracture, dento
      osseous corticotomy, and/or corticoectomy, and dental distraction. 

PMID- 24883040
TI  - Preparation of Diversely Substituted Triarylmethyl Radicals by the Quenching of
      Tris(2,3,5,6-tetrathiaaryl)methyl Cations with C-, N-, P-, and S-Nucleophiles.
AB  - C-, N-, P-, and S-nucleophiles reacted with symmetrical tris(2,3,5,6
      tetrathiaaryl)methyl cations, generated from the corresponding triarylmethanols
      by strong acids, to give a variety of asymmetrical monosubstituted persistent
      triaryl-methyl (TAM) radicals as the major products. The only byproducts were
      symmetrical TAMs.

PMID- 24883041
TI  - Characterization of Thiol-Ene Crosslinked PEG Hydrogels.
AB  - The properties of synthetic hydrogels can be tuned to address the needs of many
      tissue-culture applications. This work characterizes the swelling and mechanical
      properties of thiol-ene crosslinked PEG hydrogels made with varying prepolymer
      formulations, demonstrating that hydrogels with a compressive modulus exceeding
      600 kPa can be formed. The amount of peptide incorporated into the hydrogel is
      shown to be proportional to the amount of peptide in the prepolymer solution.
      Cell attachment and spreading on the surface of the peptide-functionalized
      hydrogels is demonstrated. Additionally, a method for bonding distinct layers of
      cured hydrogels is used to create a microfluidic channel.

PMID- 24883042
TI  - Managing Expectational Language: Translational genetic professionals consider the
      clinical potential of next-generation sequencing technologies.

PMID- 24883043
TI  - Nasopharyngeal leiomyomatous hamartoma: case report.
AB  - BACKGROUND: Fibroma, neurofibroma, and papilloma are the most commonly
      encountered benign lesions in the nasopharynx. Hamartomas are non-neoplastic
      overgrowth of mature/differentiated tissue indigenous to the specific part of the
      body in which they develop. Most hamartomas are located in the liver, spleen,
      lungs, and pancreas. However, nasopharyngeal hamartoma is rare. CASE
      PRESENTATION: We describe here a 77-year-old Japanese woman who presented with a
      mass arising from the left lateral wall of the nasopharynx. Computed tomography
      (CT) revealed a soft tissue mass without bony erosion, suggesting that the mass
      was a benign tumor such as a fibroma. Pathological examination showed that the
      mass was a leiomyomatous hamartoma. CONCLUSION: To our knowledge, this is the
      first report of a leiomyomatous hamartoma in the nasopharynx. Although
      leiomyomatous hamartoma in the nasopharynx is extremely rare, it should be kept
      in mind during differential diagnosis.

PMID- 24883044
TI  - Simulating tumor microenvironment: changes in protein expression in an in vitro
      co-culture system.
AB  - BACKGROUND: The role of the microenvironment during the initiation and
      progression of carcinogenesis is thought to be of critical importance, both for
      the enhanced understanding of fundamental cancer biology as well as for improving
      molecular diagnostics and therapeutics. The aim of this study was to establish an
      in vitro model based on a co-culture of healthy human fibroblasts (HFs) and human
      osteosarcoma cells (MG-63s) to simulate the microenvironment including tumor and
      healthy cells. METHODS: The HFs and MG-63s were in vitro co-cultured for a period
      of time ranging from 24 h to 7 days. Cell morphology and organization were
      studied using phase contrast microscopy while the expression of Human Cartilage
      Glycoprotein 39 (YKL-40), Vascular Endothelial Growth Factor (VEGF) and Matrix
      Metalloprotease 1 (MMP1) was investigated by Real Time PCR and Western Blotting.
      RESULTS: The results showed a characteristic disposition of tumor and healthy co
      cultured cells in columns which are not visible in tumor and healthy cells grown
      singularly. The expression of YKL-40, VEGF and MMP1 significantly changed in co
      cultured cells compared to HFs and MG-63s separately cultured. CONCLUSIONS: We
      concluded that the tumor microenvironment has an influence on the protein
      expression of the healthy surrounding tissues and the process of tumorigenicity.

PMID- 24883046
TI  - Assessment of vascular endothelial growth factor in formalin fixed, paraffin
      embedded colon cancer specimens by means of a well-based reverse phase protein
      array.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) is a critical pro
      angiogenic factor, found in a number of cancers, and a target of therapy. It is
      typically assessed by immunohistochemistry (IHC) in clinical research. However,
      IHC is not a quantitative assay and is rarely reproducible. We compared VEGF
      levels in colon cancer by IHC and a quantitative immunoassay on proteins isolated
      from formalin fixed, paraffin embedded tissues. RESULTS: VEGF expression was
      studied by means of a well-based reverse phase protein array (RPPA) and
      immunohistochemistry in 69 colon cancer cases, and compared with various
      clinicopathologic factors. Protein lysates derived from formalin fixed, paraffin
      embedded tissue contained measurable immunoreactive VEGF molecules. The VEGF
      expression level of well differentiated colon cancer was significantly higher
      than those with moderately and poorly differentiated carcinomas by
      immunohistochemistry (P = 0.04) and well-based RPPA (P = 0.04). VEGF
      quantification by well-based RPPA also demonstrated an association with nodal
      metastasis status (P = 0.05). In addition, the normalized VEGF value by well
      based RPPA correlated (r = 0.283, P = 0.018). Furthermore, subgroup analysis by
      histologic type revealed that adenocarcinoma cases showed significant correlation
      (r = 0.315, P = 0.031) between well-based RPPA and IHC. CONCLUSIONS: The well
      based RPPA method is a high throughput and sensitive approach, is an excellent
      tool for quantification of marker proteins. Notably, this method may be helpful
      for more objective evaluation of protein expression in cancer patients.

PMID- 24883047
TI  - Parallel classification and feature selection in microarray data using SPRINT.
AB  - The statistical language R is favoured by many biostatisticians for processing
      microarray data. In recent times, the quantity of data that can be obtained in
      experiments has risen significantly, making previously fast analyses time
      consuming or even not possible at all with the existing software infrastructure.
      High performance computing (HPC) systems offer a solution to these problems but
      at the expense of increased complexity for the end user. The Simple Parallel R
      Interface is a library for R that aims to reduce the complexity of using HPC
      systems by providing biostatisticians with drop-in parallelised replacements of
      existing R functions. In this paper we describe parallel implementations of two
      popular techniques: exploratory clustering analyses using the random forest
      classifier and feature selection through identification of differentially
      expressed genes using the rank product method.

PMID- 24883048
TI  - Measuring Attitudes Towards Empirically Supported Treatment in Real World
      Addiction Services.
AB  - Mental health workers with favorable attitudes toward empirically supported
      treatments (ESTs) are more likely to break through implementation barriers. The
      Evidence-Based Practice Attitudes Scale has been shown to be reliable for mental
      health workers, but has not been validated with addiction workers. This study
      investigates the use of the scale with a convenience sample of addiction workers
      from four agencies in one city. Results show that compared to mental health
      providers, addiction workers were more likely to view ESTs favorably if they were
      mandated and intuitively appealing. They also tended to rely more heavily on
      practical experience in forming attitudes toward treatment options. These results
      may help addiction agencies understand which types of workers are more likely to
      implement ESTs and inform effective engagement approaches specific to addiction
      workers.

PMID- 24883045
TI  - The role of cancer-associated fibroblasts, solid stress and other
      microenvironmental factors in tumor progression and therapy resistance.
AB  - Tumors are not merely masses of neoplastic cells but complex tissues composed of
      cellular and noncellular elements. This review provides recent data on the main
      components of a dynamic system, such as carcinoma associated fibroblasts that
      change the extracellular matrix (ECM) topology, induce stemness and promote
      metastasis-initiating cells. Altered production and characteristics of collagen,
      hyaluronan and other ECM proteins induce increased matrix stiffness. Stiffness
      along with tumor growth-induced solid stress and increased interstitial fluid
      pressure contribute to tumor progression and therapy resistance. Second, the role
      of immune cells, cytokines and chemokines is outlined. We discuss other
      noncellular characteristics of the tumor microenvironment such as hypoxia and
      extracellular pH in relation to neoangiogenesis. Overall, full understanding of
      the events driving the interactions between tumor cells and their environment is
      of crucial importance in overcoming treatment resistance and improving patient
      outcome. 

PMID- 24883049
TI  - Patterns of Father Self Evaluations among Mexican and European American Men and
      Links to Adolescent Adjustment.
AB  - A mixed-method study identified profiles of fathers who mentioned key dimensions
      of their parenting and linked profile membership to adolescents' adjustment using
      data from 337 European American, Mexican American and Mexican immigrant fathers
      and their early adolescent children. Father narratives about what fathers do well
      as parents were thematically coded for the presence of five fathering dimensions:
      emotional quality (how well father and child get along), involvement (amount of
      time spent together), provisioning (the amount of resources provided), discipline
      (the amount and success in parental control), and role modeling (teaching life
      lessons through example). Next, latent class analysis was used to identify three
      patterns of the likelihood of mentioning certain fathering dimensions: an
      emotionally-involved group mentioned emotional quality and involvement; an
      affective-control group mentioned emotional quality, involvement, discipline and
      role modeling; and an affective-model group mentioned emotional quality and role
      modeling. Profiles were significantly associated with subsequent adolescents'
      reports of adjustment such that adolescents of affective-control fathers reported
      significantly more externalizing behaviors than adolescents of emotionally
      involved fathers.

PMID- 24883050
TI  - Combined ecological momentary assessment and global positioning system tracking
      to assess smoking behavior: a proof of concept study.
AB  - OBJECTIVE: Ecological momentary assessment (EMA) methods have provided a rich
      assessment of the contextual factors associated with a wide range of behaviors
      including alcohol use, eating, physical activity, and smoking. Despite this rich
      database, this information has not been linked to specific locations in space.
      Such location information, which can now be easily acquired from global
      positioning system (GPS) tracking devices, could provide unique information
      regarding the space-time distribution of behaviors and new insights into their
      determinants. In a proof of concept study, we assessed the acceptability and
      feasibility of acquiring and combining EMA and GPS data from adult smokers with
      attention deficit hyperactivity disorder (ADHD). METHODS: Participants were
      adults with ADHD who were enrolled in a larger EMA study on smoking and
      psychiatric symptoms. Among those enrolled in the latter study who were
      approached to participate (N = 11), 10 consented, provided daily EMA entries, and
      carried a GPS device with them during a 7-day assessment period to assess aspects
      of their smoking behavior. RESULTS: The majority of those eligible to participate
      were willing to carry a GPS device and signed the consent (10 out of 11, 91%). Of
      the 10 who consented, 7 participants provided EMA entries and carried the GPS
      device with them daily for at least 70% of the sampling period. Data are
      presented on the spatial distribution of smoking episodes and ADHD symptoms on a
      subset of the sample to demonstrate applications of GPS data. CONCLUSIONS: We
      conclude by discussing how EMA and GPS might be used to study the ecology of
      smoking and make recommendations for future research and analysis.

PMID- 24883051
TI  - The Adult Roles Models Program: Feasibility, Acceptability, and Initial Outcomes.
AB  - We present the feasibility and acceptability of a parent sexuality education
      program led by peer educators in community settings. We also report the results
      of an outcome evaluation with 71 parents who were randomized to the intervention
      or a control group, and surveyed one month prior to and six months after the 4
      week intervention. The program was highly feasible and acceptable to
      participants, and the curriculum was implemented with a high level of fidelity
      and facilitator quality. Pilot data show promising outcomes for increasing
      parental knowledge, communication, and monitoring of their adolescent children.

PMID- 24883052
TI  - A Practical Synthesis and X-ray Crystallographic Analysis of Dithymoquinone, a
      Photodimer of Thymoquinone.
AB  - An updated and practical approach to the synthesis of dithymoquinone via one-step
      photoirradiation of thymoquinone (2-methyl-5-isopropyl-1,4-benzoquinone) is
      described. Synthesis resulted in a 55% yield of one structural isomer (trans-anti
      derivative), as confirmed by HPLC, NMR spectroscopy and first ever single-crystal
      X-ray diffraction analyses.

PMID- 24883053
TI  - Radial stem growth in response to microclimate and soil moisture in a drought
      prone mixed coniferous forest at an inner Alpine site.
AB  - Dendroclimatological studies in a dry inner Alpine environment (750 m a.s.l.)
      revealed different growth response of co-occurring coniferous species to climate,
      which is assumed to be caused by a temporal shift in wood formation among
      species. The main focus of this study therefore was to monitor intra-annual
      dynamics of radial increment growth of mature deciduous and evergreen coniferous
      species (Pinus sylvestris, Larix decidua and Picea abies) during two consecutive
      years with contrasting climatic conditions. Radial stem growth was continuously
      followed by band dendrometers and modelled using Gompertz functions to determine
      time of maximum growth. Histological analyses of tree ring formation allowed
      determination of temporal dynamics of cambial activity and xylem cell
      development. Daily fluctuations in stem radius and radial stem increments were
      extracted from dendrometer traces, and correlations with environmental variables
      were performed. While a shift in temporal dynamics of radial growth onset and
      cessation was detected among co-occurring species, intra-annual radial growth
      peaked synchronously in late May 2011 and early June 2012. Moist atmospheric
      conditions, i.e. high relative air humidity, low vapour pressure deficit and low
      air temperature during the main growing period, favoured radial stem increment of
      all species. Soil water content and soil temperature were not significantly
      related to radial growth. Although a temporal shift in onset and cessation of
      wood formation was detected among species, synchronous culmination of radial
      growth indicates homogenous exogenous and/or endogenous control. The close
      coupling of radial growth to atmospheric conditions points to the importance of
      stem water status for intra-annual growth of drought-prone conifers.

PMID- 24883054
TI  - Stenting and angioplasty of small cerebral arteries in symptomatic intracranial
      atherosclerotic disease.
AB  - BACKGROUND: Intracranial atherosclerotic disease (ICAD) is a common cause of
      stroke with a poor natural history despite medical therapy. Few studies have
      investigated endovascular therapies for the treatment of symptomatic ICAD in
      distal intracranial arteries. Here, we present the feasibility and safety of
      balloon angioplasty with and without stenting in patients with medically
      refractory small artery symptomatic ICAD. METHOD: Personal logs were reviewed to
      identify patients who were treated for small artery ICAD (stenosis > 50%) using
      angioplasty +/- stenting. Small cerebral arteries were defined by a diameter <= 2
      mm or any branch distal to a large intracranial vessel (i.e. distal to ICA, M1,
      A1, Vertebrobasilar trunk). Patient characteristics, clinical manifestations,
      treatment, hospital course, and follow up data was collected and analyzed.
      RESULTS: Ten patients (12 arteries) were treated with either primary balloon
      angioplasty (58.3%) or angioplasty with stenting (41.6 %) with 100% technical
      success rate. Mean pre-treatment stenosis was 79.9% while mean post-treatment
      stenosis was 19.0%. There were no major peri-procedural complications including
      symptomatic intracranial hemorrhage or mortality; three cases were complicated by
      groin hematoma. Patients were followed for a mean total of 18.6 months with only
      one symptomatic restenosis which was re-treated successfully. All patients had
      good functional outcome with a mRS of either 0 (80%) or 1 (20%) on follow up.
      CONCLUSION: In our case series, treatment of symptomatic small artery ICAD with
      angioplasty +/- stenting was safe and effective. These interventions should be
      considered as an alternative treatment for ICAD patients refractory to medical
      therapy.

PMID- 24883055
TI  - Opioid-induced constipation: pathophysiology, clinical consequences, and
      management.
AB  - Although opioids offer potent analgesia for severe acute and chronic noncancer
      pain, adverse gastrointestinal effects potentially undermine their clinical
      utility. In particular, between 40% and 95% of patients develop opioid-induced
      constipation (OIC). Therefore, there is a consensus that patients should commence
      laxatives at the start of opioid therapy and continue throughout treatment.
      Nevertheless, laxatives are not routinely coprescribed with opioids. Even when
      concurrent laxatives are prescribed, approximately half the patients treated for
      OIC do not achieve the desired improvement. Moreover, laxatives do not target the
      underlying cause of OIC (opioid binding to the MU -receptors in the enteric
      system) and as such are not very effective at managing OIC. The failure of
      lifestyle modification and laxatives to treat adequately many cases of OIC led to
      the concurrent use of peripherally acting opioid antagonists (such as
      methylnaltrexone bromide and naloxone) to reduce the incidence of
      gastrointestinal adverse events without compromising analgesia. Judicious use of
      the various options to manage OIC should allow more patients to benefit from
      opioid analgesia. Therefore, this paper reviews the causes, consequences, and
      management of OIC to help clinicians optimise opioid analgesia. 

PMID- 24883056
TI  - ATP-Binding Cassette Genes Genotype and Expression: A Potential Association with
      Pancreatic Cancer Development and Chemoresistance?
AB  - Genetic polymorphisms in ABC (ATP-binding cassette) transporter genes are
      associated with differential responses to chemotherapy in various cancers
      including pancreatic cancer. In this study, four SNPs in the ABCB1, ABCC1, and
      ABCG2 genes were investigated in normal and pancreatic cancerous specimens. The
      expression of the three transporters was also analyzed. The TT genotypes of
      G2677T and C3435T in ABCB1 gene were associated with lower risk of developing
      pancreatic cancer (P = 0.013, OR = 0.35 and P = 0.015, OR = 0.29, resp.). To our
      knowledge, this is the first report of the common polymorphisms in the ABCB1 gene
      affecting the genetic risk of developing pancreatic cancer. Moreover, the
      expression of ABCB1 in 2677TT and 3435TT carriers was lower compared to the wild
      type homozygotes and heterozygotes. A cell viability assay, using standard
      pancreatic cancer cell lines, revealed that the ABCB1 2677TT-3455TT haplotype was
      more sensitive than the other haplotypes to gemcitabine. Conclusion.
      Polymorphisms in ABCB1 G2677T and G3435T were associated with differential
      susceptibility to pancreatic cancer and may predict responses to chemotherapy. 

PMID- 24883057
TI  - MDCT of Small Bowel Obstruction: How Reliable Are Oblique Reformatted Images in
      Localizing Point of Transition?
AB  - The goal of this study is to prospectively assess the additional value of oblique
      reformatted images for localizing POT, having surgery as a reference standard.
      Materials and Methods. 102 consecutive patients with suspected small bowel
      obstruction (SBO) underwent 64-slice multidetector row CT (MDCT) using surgical
      findings as reference standard. Two independent GI radiologists reviewed the CT
      scans to localize the exact POT by evaluating axial images (data set A) followed
      by axial, coronal, and oblique MPR images. CT findings were compared to surgical
      findings in terms of diagnostic performance. McNemar's test was used to detect
      any statistical difference in POT evaluation between datasets A and B. Kappa
      statistics were applied for measuring agreement between two readers. Results.
      There was a diagnostic improvement of 9.9% in the case of the less experienced
      radiologist in localizing POT by using oblique reformatted images. The more
      experienced radiologist showed diagnostic improvement by 12.9%. 

PMID- 24883058
TI  - Influence of flunixin on the disposition kinetic of cefepime in goats.
AB  - The pharmacokinetic profile of cefepime (10 mg/kg b.w.) was studied following
      intravenous and intramuscular administration of cefepime alone and coadministered
      with flunixin (2.2 mg/kg b.w.) in goats. Cefepime concentrations in serum were
      determined by microbiological assay technique using Escherichia coli (MTCC 443)
      as test organism. Following intravenous injection of cefepime alone and in
      combination with flunixin, there are no significant changes in the
      pharmacokinetic parameters. Following intramuscular injection of cefepime alone
      and in combination with flunixin, the maximum serum concentration was
      significantly increased in flunixin coadministered group compared with cefepime
      alone. However, no significant changes were reported in other pharmacokinetic
      parameters. The result of in vitro protein binding study indicated that 15.62% of
      cefepime was bound to goat's serum protein. The mean bioavailability was 92.66%
      and 95.27% in cefepime alone and coadministered with flunixin, respectively. The
      results generated from the present study suggest that cefepime may be
      coadministered with flunixin without change in dose regimen. Cefepime may be
      given intramuscularly at 12 h intervals to combat susceptible bacterial
      infections. 

PMID- 24883059
TI  - A wireless emergency telemedicine system for patients monitoring and diagnosis.
AB  - Recently, remote healthcare systems have received increasing attention in the
      last decade, explaining why intelligent systems with physiology signal monitoring
      for e-health care are an emerging area of development. Therefore, this study
      adopts a system which includes continuous collection and evaluation of multiple
      vital signs, long-term healthcare, and a cellular connection to a medical center
      in emergency case and it transfers all acquired raw data by the internet in
      normal case. The proposed system can continuously acquire four different
      physiological signs, for example, ECG, SpO2, temperature, and blood pressure and
      further relayed them to an intelligent data analysis scheme to diagnose abnormal
      pulses for exploring potential chronic diseases. The proposed system also has a
      friendly web-based interface for medical staff to observe immediate pulse signals
      for remote treatment. Once abnormal event happened or the request to real-time
      display vital signs is confirmed, all physiological signs will be immediately
      transmitted to remote medical server through both cellular networks and internet.
      Also data can be transmitted to a family member's mobile phone or doctor's phone
      through GPRS. A prototype of such system has been successfully developed and
      implemented, which will offer high standard of healthcare with a major reduction
      in cost for our society. 

PMID- 24883061
TI  - Neuroinflammation and oxidative stress in diabetic neuropathy: futuristic
      strategies based on these targets.
AB  - In Diabetes, the chronic hyperglycemia and associated complications affecting
      peripheral nerves are one of the most commonly occurring microvascular
      complications with an overall prevalence of 50-60%. Among the vascular
      complications of diabetes, diabetic neuropathy is the most painful and disabling,
      fatal complication affecting the quality of life in patients. Several theories of
      etiologies surfaced down the lane, amongst which the oxidative stress mediated
      damage in neurons and surrounding glial cell has gained attention as one of the
      vital mechanisms in the pathogenesis of neuropathy. Mitochondria induced ROS and
      other oxidants are responsible for altering the balance between oxidants and
      innate antioxidant defence of the body. Oxidative-nitrosative stress not only
      activates the major pathways namely, polyol pathway flux, advanced glycation end
      products formation, activation of protein kinase C, and overactivity of the
      hexosamine pathway, but also initiates and amplifies neuroinflammation. The cross
      talk between oxidative stress and inflammation is due to the activation of NF-
      kappa B and AP-1 and inhibition of Nrf2, peroxynitrite mediate endothelial
      dysfunction, altered NO levels, and macrophage migration. These all culminate in
      the production of proinflammatory cytokines which are responsible for nerve
      tissue damage and debilitating neuropathies. This review focuses on the
      relationship between oxidative stress and neuroinflammation in the development
      and progression of diabetic neuropathy. 

PMID- 24883062
TI  - Circulating fractalkine levels predict the development of the metabolic syndrome.
AB  - The fractalkine/CX3CR1 axis plays an important role in regulating glucose and
      lipid metabolism. However, the role of fractalkine in metabolic disorders remains
      to be fully elucidated. We selected 887 Chinese (40-65 years old) at baseline,
      with a subgroup of 459 participants examined again 2 years later. The
      relationship of serum fractalkine levels with the metabolic syndrome (MetS) and
      its components was investigated. At baseline, participants with MetS had higher
      fractalkine concentrations than their counterparts without MetS (P < 0.001). At
      the 2-year follow-up, participants in the highest quartile of baseline
      fractalkine exhibited higher values for body mass index, waist circumference,
      waist-to-hip ratio, body fat percentage, glucose, insulin, total cholesterol,
      triglycerides (TG), and homeostasis model assessment of insulin resistance (HOMA
      IR) and lower value for high density lipoprotein-cholesterol (HDL-c) (all P <
      0.05). Among 390 participants without MetS at baseline, 45 developed it at year
      2. Even after multiple adjustments for visceral adipose tissue area, HOMA-IR, C
      reactive protein (CRP), or TG and HDL-c, baseline fractalkine predicted the
      development of MetS (OR = 7.18, 95%CI: 2.28-18.59). In conclusion, circulating
      fractalkine predicts the development of the MetS independently of central
      obesity, CRP, insulin resistance, and dyslipidemia. 

PMID- 24883060
TI  - Inflammatory response in islet transplantation.
AB  - Islet cell transplantation is a promising beta cell replacement therapy for
      patients with brittle type 1 diabetes as well as refractory chronic pancreatitis.
      Despite the vast advancements made in this field, challenges still remain in
      achieving high frequency and long-term successful transplant outcomes. Here we
      review recent advances in understanding the role of inflammation in islet
      transplantation and development of strategies to prevent damage to islets from
      inflammation. The inflammatory response associated with islets has been
      recognized as the primary cause of early damage to islets and graft loss after
      transplantation. Details on cell signaling pathways in islets triggered by
      cytokines and harmful inflammatory events during pancreas procurement, pancreas
      preservation, islet isolation, and islet infusion are presented. Robust control
      of pre- and peritransplant islet inflammation could improve posttransplant islet
      survival and in turn enhance the benefits of islet cell transplantation for
      patients who are insulin dependent. We discuss several potent anti-inflammatory
      strategies that show promise for improving islet engraftment. Further
      understanding of molecular mechanisms involved in the inflammatory response will
      provide the basis for developing potent therapeutic strategies for enhancing the
      quality and success of islet transplantation. 

PMID- 24883063
TI  - Evaluation of Heart Rate Assessment Timing, Communication, Accuracy, and Clinical
      Decision-Making during High Fidelity Simulation of Neonatal Resuscitation.
AB  - Objective. Accurate heart rate (HR) determination during neonatal resuscitation
      (NR) informs subsequent NR actions. This study's objective was to evaluate HR
      determination timeliness, communication, and accuracy during high fidelity NR
      simulations that house officers completed during neonatal intensive care unit
      (NICU) rotations. Methods. In 2010, house officers in NICU rotations completed
      high fidelity NR simulation. We reviewed 80 house officers' videotaped
      performance on their initial high fidelity simulation session, prior to training
      and performance debriefing. We calculated the proportion of cases congruent with
      NR guidelines, using chi square analysis to evaluate performance across HR ranges
      relevant to NR decision-making: <60, 60-99, and >=100 beats per minute (bpm).
      Results. 87% used umbilical cord palpation, 57% initiated HR assessment within 30
      seconds, 70% were accurate, and 74% were communicated appropriately. HR
      determination accuracy varied significantly across HR ranges, with 87%, 57%, and
      68% for HR <60, 60-99, and >=100 bpm, respectively (P < 0.001). Conclusions.
      Timeliness, communication, and accuracy of house officers' HR determination are
      suboptimal, particularly for HR 60-100 bpm, which might lead to inappropriate
      decision-making and NR care. Training implications include emphasizing more
      accurate HR determination methods, better communication, and improved HR
      interpretation during NR. 

PMID- 24883064
TI  - Proteolytic Activity Present in House-Dust-Mite Extracts Degrades ENA-78/CXCL5
      and Reduces Neutrophil Migration.
AB  - Background. Bronchial smooth muscle cells (BSMC) are a major source of
      proinflammatory and proangiogenic cytokines and chemokines, including VEGF and
      CXC-chemokines. CXC-chemokines act primarily on neutrophils, mediating their
      recruitment to and activation at the site of inflammation. In humans, house-dust
      mite (HDM) allergens can cause asthmatic exacerbations and trigger an
      inflammatory response through protease-dependent mechanisms. Objective. We
      investigated the effect HDM extract on the release of pro-angiogenic and
      proinflammatory cytokines from BSMC. Methods. Human primary BSMC were stimulated
      with HDM extract in the absence or presence of fetal calf serum (FCS). Twenty
      angiogenic cytokines were detected by a specific antibody array and modified
      protein levels were confirmed by ELISA. Neutrophil migration was measured using a
      96-well Boyden chamber. Results. ENA-78/CXCL5 protein levels in conditioned
      medium of BSMC stimulated with HDM extract were significantly reduced (n = 10, P
      < 0.05) but restored in the presence of 5% FCS. HDM extracts did not affect ENA
      78/CXCL5 mRNA levels. Recombinant ENA-78/CXCL5 was degraded after incubation with
      HDM extracts (n = 7, P < 0.05) but restored after the addition of the serine
      protease AEBSF. Neutrophil migration towards recombinant ENA-78/CXCL5 was also
      reduced in the presence of HDM extract. Conclusion. HDM proteases degrade ENA
      78/CXCL5. Thus exposure to HDM allergens may alter ENA-78/CXCL5 levels in the
      lungs and may affect angiogenesis and the inflammatory response in the airways of
      asthma patients. 

PMID- 24883065
TI  - Significant gender difference in serum levels of fibroblast growth factor 21 in
      Danish children and adolescents.
AB  - INTRODUCTION: Fibroblast Growth Factor 21 (FGF21) is a novel metabolic factor
      with effect on glucose and lipid metabolism, and shown to be elevated in diseases
      related to metabolic syndrome. Due to the increasing frequency of metabolic
      syndrome in the pediatric population, and as FGF21 studies in children are
      limited, we investigated baseline serum levels of FGF21 in healthy children
      during an oral glucose tolerance test. METHODS: A total of 179 children and
      adolescents from the COPENHAGEN Puberty Study were included. An OGTT with glucose
      and insulin measurements, a dual energy X-ray absorptiometry (DXA) scan and a
      clinical examination including pubertal staging were done on all subjects. Serum
      levels of FGF21, adiponectin, and leptin were determined by immunoassays at
      baseline. RESULTS: The girls had significantly higher levels of FGF21 compared
      with boys (155 pg/mL vs. 105 pg/mL, P = 0.04). 38 children (21%) had levels below
      detection limit of assay. Baseline levels of FGF21 showed positive correlation
      with triglycerides, but no significant correlations were found between FGF21
      concentration and body mass index (BMI), DXA-derived fat percentage, LDL- HDL-
      and non-HDL cholesterol, leptin or adiponectin levels, respectively. Neither was
      any correlation found between baseline FGF21-levels and the dynamic changes in
      glucose and insulin levels during the OGTT. CONCLUSION: FGF21 is independent of
      adiposity in children, and the significant metabolic effect seems to be limited
      to pathological conditions associated with insulin resistance. The higher levels
      of triglycerides in the girls may explain the significantly higher levels of
      FGF21 in girls compared with boys. SYSTEMATIC REVIEW REGISTRATION: The COPENHAGEN
      Puberty Study was registered in ClinicalTrials.gov (identifier NCT01411527), and
      approved by the local ethics committee (reference no. KF 01 282214 and KF 11 2006
      2033).

PMID- 24883066
TI  - ERK1/2-Egr-1 Signaling Pathway-Mediated Protective Effects of Electroacupuncture
      in a Mouse Model of Myocardial Ischemia-Reperfusion.
AB  - Early growth response- (Egr-) 1 is an upstream master switch in controlling
      inflammatory responses following myocardial ischemia-reperfusion (I/R).
      Activation of extracellular signal-regulated protein kinase-1 and kinase-2
      (ERK1/2) signaling is known to upregulate Egr-1. ERK1/2 pathway has been
      previously shown to mediate the therapeutic action of electroacupucture (EA).
      Thus, we hypothesized that EA would reduce myocardial I/R injury and inflammatory
      responses through inhibiting Egr-1 expression via the ERK1/2 pathway. Mice were
      pretreated with EA, U0126, or combination of EA and U0126 and then underwent 1 h
      myocardial ischemia and 3 h reperfusion. We investigated that EA significantly
      attenuated the I/R-induced upregulation of both Egr-1 and phosporylated-ERK1/2 (p
      ERK1/2), decreased myocardial inflammatory cytokines including tumor necrosis
      factor- alpha (TNF- alpha ) and interleukin-1 beta (IL-1 beta ), and reduced the
      infarct size and the release of cardiac troponin I (cTnI). U0126 treatment also
      exhibited the same effect as EA on Egr-1 level and subsequent cardioprotective
      effects. There was no additive effect of cotreatment with EA and U0126 on the
      expression of Egr-1 and its downstream target genes (TNF- alpha , IL-1 beta ) or
      serum cTnI level. Collectively, these observations suggested that EA attenuates
      myocardial I/R injury, possibly through inhibiting the ERK1/2-Egr-1 signaling
      pathway and reducing the release of proinflammatory cytokines. 

PMID- 24883067
TI  - The physiological and biochemical outcomes associated with a reflexology
      treatment: a systematic review.
AB  - Background. Reflexology is one of the top forms of complementary and alternative
      medicine in the UK and is used for healthcare by a diverse range of people.
      However, it is offered by few healthcare providers as little scientific evidence
      is available explaining how it works or any health benefits it may confer. The
      aim of this review was to assess the current evidence available from reflexology
      randomised controlled trials (RCTs) that have investigated changes in
      physiological or biochemical outcomes. Methods. Guidelines from the Cochrane
      Handbook of Systematic Reviews of Interventions were followed: the following
      databases were searched from inception to December 2013: AMED, CAM Quest, CINAHL
      Plus, Cochrane Central Register of Controlled Trials, Embase, Medline Ovid,
      Proquest, and Pubmed. Risk of bias was assessed independently by two members of
      the review team and overall strength of the evidence was assessed using the
      Grading of Recommendations, Assessment, Development, and Evaluation guidelines.
      Results. Seventeen eligible RCTs met all inclusion criteria. A total of 34
      objective outcome measures were analysed. Although twelve studies showed
      significant changes within the reflexology group, only three studies
      investigating blood pressure, cardiac index, and salivary amylase resulted in
      significant between group changes in favour of reflexology. The overall quality
      of the studies was low. 

PMID- 24883068
TI  - Objective Auscultation of TCM Based on Wavelet Packet Fractal Dimension and
      Support Vector Machine.
AB  - This study was conducted to illustrate that auscultation features based on the
      fractal dimension combined with wavelet packet transform (WPT) were conducive to
      the identification the pattern of syndromes of Traditional Chinese Medicine
      (TCM). The WPT and the fractal dimension were employed to extract features of
      auscultation signals of 137 patients with lung Qi-deficient pattern, 49 patients
      with lung Yin-deficient pattern, and 43 healthy subjects. With these features,
      the classification model was constructed based on multiclass support vector
      machine (SVM). When all auscultation signals were trained by SVM to decide the
      patterns of TCM syndromes, the overall recognition rate of model was 79.49%; when
      male and female auscultation signals were trained, respectively, to decide the
      patterns, the overall recognition rate of model reached 86.05%. The results
      showed that the methods proposed in this paper were effective to analyze
      auscultation signals, and the performance of model can be greatly improved when
      the distinction of gender was considered. 

PMID- 24883069
TI  - Anti-Inflammatory Effects of the Bioactive Compound Ferulic Acid Contained in
      Oldenlandia diffusa on Collagen-Induced Arthritis in Rats.
AB  - Objectives. This study aimed to identify the active compounds in Oldenlandia
      diffusa (OD) decoction and the compounds absorbed into plasma, and to determine
      whether the absorbed compounds derived from OD exerted any anti-inflammatory
      effects in rats with collagen induced arthritis (CIA). Methods. The UPLC-PDA
      (Ultra Performance Liquid Chromatography Photo-Diode Array) method was applied to
      identify the active compounds both in the decoction and rat plasma. The
      absorbable compound was administered to the CIA rats, and the effects were
      dynamically observed. X-ray films of the joints and HE stain of synovial tissues
      were analyzed. The levels of IL-1 beta and TNF- alpha in the rats from each group
      were measured by means of ELISA. The absorbed compound in the plasma of CIA rats
      was identified as ferulic acid (FA), following OD decoction administration. Two
      weeks after the administration of FA solution or OD decoction, the general
      conditions improved compared to the model group. The anti-inflammatory effect of
      FA was inferior to that of the OD decoction (P < 0.05), based on a comparison of
      IL-1 beta TNF- alpha levels. FA from the OD decoction was absorbed into the body
      of CIA rats, where it elicited anti-inflammatory responses in rats with CIA.
      Conclusions. These results suggest that FA is the bioactive compound in OD
      decoction, and FA exerts its effects through anti-inflammatory pathways. 

PMID- 24883071
TI  - Evaluation of the Antihyperuricemic Activity of Phytochemicals from Davallia
      formosana by Enzyme Assay and Hyperuricemic Mice Model.
AB  - Abnormal serum urate levels are recognized as a critical factor in the
      progression of several chronic diseases. To evaluate the antihyperuricemic effect
      of Davallia formosana, the inhibitory activities of 15 isolated phytochemicals,
      including five novel compounds of 6,8-dihydroxychromone-7-C- beta -d
      glucopyranoside (1), 6,8,3',4'-tetrahydroxyflavanone-7-C- beta -d-glucopyranoside
      (2), 6,8,4'-trihydroxyflavanone-7-C- beta -d-glucopyranoside (3), 8-(2
      pyrrolidinone-5-yl)-catechin-3-O- beta -d-allopyranoside (4), and
      epiphyllocoumarin-3-O- beta -d-allopyranoside (5), were examined against xanthine
      oxidase (XOD) and in a potassium oxonate-(PTO-) induced acute hyperuricemic mice
      model. The results indicated that compounds 3 and 5 significantly inhibited XOD
      activity in vitro and reduced serum uric acid levels in vivo. This is the first
      report providing new insights into the antihyperuricemic activities of flavonoid
      glycosides which can possibly be developed into potential hypouricemic agents. 

PMID- 24883070
TI  - Extracts from Curcuma zedoaria Inhibit Proliferation of Human Breast Cancer Cell
      MDA-MB-231 In Vitro.
AB  - Objective. To evaluate the effect of petroleum ether extracts of Curcuma zedoaria
      on the proliferation of human triple negative breast cancer cell line MDA-MB-231.
      Methods. The reagents were isolated from Curcuma zedoaria by petroleum ether
      fraction. It was assayed by CCK8 for MDA-MB-231 cellular viability with various
      concentrations and days, cell cycle analyses, Western Blot analysis, and Realtime
      Reverse Transcriptase PCR analyses for chemokines molecules including E-cadherin,
      and E-selectin, and adhesion molecules including CCR7, SLC, SDF-1, and CXCR4.
      Epirubicin was used as control in the study. Results. MDA-MB-231 cells were
      inhibited by petroleum ether extracts of Curcuma zedoaria (P < 0.05), and the
      inhibition rate was dependent on concentrations and time. Petroleum ether
      extracts of Curcuma zedoaria as well as Epirubicin produce a significant G0/G1
      cell cycle arrest. The level of expression of proteins E-cadherin and E-cadherin
      mRNA was significantly increased, while proteins SDF-1, CCR7, and CXCR4 mRNA were
      decreased after being incubated with petroleum ether extracts of Curcuma zedoaria
      at the concentrations of 300  MU g/mL than control (P < 0.05). The differences
      were that the protein CXCR4 mRNA expression level was higher than vehicle.
      Conclusions. MDA-MB-231 cells were inhibited by petroleum ether extracts of
      Curcuma zedoaria. 

PMID- 24883073
TI  - An Immunomodulatory Protein (Ling Zhi-8) from a Ganoderma lucidum Induced
      Acceleration of Wound Healing in Rat Liver Tissues after Monopolar
      Electrosurgery.
AB  - The purpose of this study was to investigate the effect of an immunomodulatory
      protein (Ling Zhi-8, LZ-8) on wound healing in rat liver tissues after monopolar
      electrosurgery. Animals were sacrificed for evaluations at 0, 3, 7, and 28 days
      postoperatively. It was found that the wound with the LZ-8 treatment
      significantly increases wound healing. Western blot analysis clearly indicated
      that the expression of NF-kappaB was decreased at 3, 7, and 28 days when liver
      tissues were treated with LZ-8. Moreover, caspase-3 activity of the liver tissue
      also significantly decreases at 7 and 28 days, respectively. DAPI staining and
      TUNEL assays revealed that only a minimal dispersion of NF-kappaB was found on
      the liver tissue treated with LZ-8 at day 7 as compared with day 3 and tissues
      without LZ-8 treatment. Similarly, apoptosis was decreased on liver tissues
      treated with LZ-8 at 7 days when compared to the control (monopolar
      electrosurgery) tissues. Therefore, the analytical results demonstrated that LZ-8
      induced acceleration of wound healing in rat liver tissues after monopolar
      electrosurgery. 

PMID- 24883072
TI  - Recent advances in developing insect natural products as potential modern day
      medicines.
AB  - Except for honey as food, and silk for clothing and pollination of plants, people
      give little thought to the benefits of insects in their lives. This overview
      briefly describes significant recent advances in developing insect natural
      products as potential new medicinal drugs. This is an exciting and rapidly
      expanding new field since insects are hugely variable and have utilised an
      enormous range of natural products to survive environmental perturbations for
      100s of millions of years. There is thus a treasure chest of untapped resources
      waiting to be discovered. Insects products, such as silk and honey, have already
      been utilised for thousands of years, and extracts of insects have been produced
      for use in Folk Medicine around the world, but only with the development of
      modern molecular and biochemical techniques has it become feasible to manipulate
      and bioengineer insect natural products into modern medicines. Utilising
      knowledge gleaned from Insect Folk Medicines, this review describes modern
      research into bioengineering honey and venom from bees, silk, cantharidin,
      antimicrobial peptides, and maggot secretions and anticoagulants from blood
      sucking insects into medicines. Problems and solutions encountered in these
      endeavours are described and indicate that the future is bright for new insect
      derived pharmaceuticals treatments and medicines. 

PMID- 24883074
TI  - Past hybridization between two East Asian long-tailed tits (Aegithalos bonvaloti
      and A. fuliginosus).
AB  - INTRODUCTION: Incomplete lineage sorting and hybridization are two major
      nonexclusive causes of haplotype sharing between species. Distinguishing between
      these two processes is notoriously difficult as they can generate similar genetic
      signatures. Previous studies revealed that the mitochondrial DNA (mtDNA)
      differentiation between two East Asian long-tailed tits (Aegithalos bonvaloti and
      A. fuliginosus) was extremely low, even lower than intraspecific differentiation
      in some other long-tailed tits. Using a combination of multilocus and coalescent
      analyses, we explored the causes of the anomalous lack of mtDNA differentiation
      between the two species. RESULTS: The mtDNA divergence between the two species
      was shallow, while the nuclear DNA (nuDNA) divergence was considerably deeper.
      The IMa analyses based on the mtDNA dataset suggested relatively high gene flow
      from A. fuliginosus to A. bonvaloti, while negligible gene flow in the opposite
      direction. In contrast to mtDNA, the migration rates at autosomal and Z-linked
      nuDNA loci were negligible or much lower. The NEWHYBRIDS analysis assigned all
      individuals except one to pure parental species with high posterior probability.
      The Bayesian skyline plot showed that both species underwent population
      expansions during the Last Glacial Maximum (LGM), and the ecological niche
      modelling suggested that their ranges overlapped more during the LGM than at
      present. CONCLUSIONS: We suggest that historical hybridization, in combination
      with selective sweep and/or genetic drift might be the main causes of the
      extremely low mtDNA differentiation between the two species. The hybridization
      probably occurred mainly between A. fuliginosus females and A. bonvaloti males.
      The LGM distribution expansion might have facilitated hybridization, while the
      post-LGM distribution contraction could have facilitated some mtDNA sorting.
      Ongoing hybridization between the two species might be very limited, but further
      studies with more samples from the contact zone are needed to test this
      conclusion.

PMID- 24883075
TI  - Abdominal obesity is an independent predictor of serum 25-hydroxyvitamin D
      deficiency in adults with cerebral palsy.
AB  - BACKGROUND: Individuals with cerebral palsy (CP) are at risk for nutritional
      insufficiency. The purpose of the study was to examine the vitamin D status of
      adults with CP, and to evaluate the association between vitamin D and functional
      level, age, race, and anthropometric indicators of adiposity. METHODS: Serum
      vitamin D levels, BMI, waist circumference (WC), and functional level (measured
      by Gross Motor Function Classification System (GMFCS)) were examined in 112
      adults with CP. Vitamin D status was assessed by serum 25-hydroxyvitamin D level
      (25(OH)D). The influence of motor impairment and adiposity on 25(OH)D were
      assessed using general linear modeling and logistic regression, with age, sex,
      race, and season as covariates. RESULTS: Mean vitamin D was 28.1 +/- 16.0 ng/ml.
      Only 45% of subjects had optimal levels of 25(OH)D, 21% were insufficient and 34%
      were deficient. Overweight or obesity was prevalent (52%), as was abdominal
      obesity in men (23.5% at 102 cm cutoff) and women (31.1% at 88 cm cutoff). There
      was a robust association between the indicator of visceral adiposity (WC) and
      25(OH)D level (p <0.001), even after controlling for age, sex, race, season, and
      GMFCS. According to sex-specific WC cutoffs, the odds of being deficient in
      vitamin D increase by a factor of 3.5 (95% CI 1.12-11.0) for abdominal obesity.
      GMFCS was not associated with 25(OH)D. CONCLUSIONS: Adults with CP are at risk
      for low vitamin D levels and overweight/obesity. Waist circumference is a strong
      independent predictor for low vitamin D levels.

PMID- 24883076
TI  - Education Fever and the East Asian Fertility Puzzle: A case study of low
      fertility in South Korea.
AB  - Fertility throughout East Asia has fallen rapidly over the last five decades and
      is now below the replacement rate of 2.1 in every country in the region. Using
      South Korea as a case study, we argue that East Asia's ultra-low fertility rates
      can be partially explained by the steadfast parental drive to have competitive
      and successful children. Parents throughout the region invest large amounts of
      time and money to ensure that their children are able to enter prestigious
      universities and obtain top jobs. Accordingly, childrearing has become so
      expensive that the average couple cannot afford to have more than just one or two
      children. The trend of high parental investment in child education, also known as
      'education fever', exemplifies the notion of 'quality over quantity' and is an
      important contributing factor to understanding low-fertility in East Asia.

PMID- 24883077
TI  - Statistical evaluation of reproducibility of automated ECG measurements: an
      example from arrhythmogenic right ventricular dysplasia/cardiomyopathy clinic.
AB  - BACKGROUND: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is
      characterized by delay in depolarization of the right ventricle, detected by
      prolonged terminal activation duration (TAD) in V1-V3. However, manual ECG
      measurements have shown moderate-to-low intra- and inter-reader agreement. The
      goal of this study was to assess reproducibility of automated ECG measurements in
      the right precordial leads. METHODS: Pairs of ECGs recorded in the same day from
      Johns Hopkins ARVD/C Registry participants [n=247, mean age 35.2+/-15.6 y, 58%
      men, 92% whites, 11(4.5%) with definite ARVD/C] were retrospectively analyzed.
      QRS duration, intrinsicoid deflection, TAD, and T-wave amplitude in the right
      precordial leads, as well as averaged across all leads QRS duration, QRS axis, T
      axis, QTc interval, and heart rate was measured automatically, using 12SL TM
      algorithm (GE Healthcare, Wauwatosa, WI, USA). Intrinsicoid deflection was
      measured as the time from QRS complex onset to the alignment point of the QRS
      complex. TAD was calculated as the difference between QRS duration and
      intrinsicoid in V1, V2, V3. Reproducibility was quantified by Bland-Altman
      analysis (bias with 95% limits of agreement), Lin's concordance coefficient, and
      Bradley-Blackwood procedure. RESULTS: Bland-Altman analysis revealed satisfactory
      reproducibility of tested parameters. V1 QRS duration bias was -0.10ms [95%
      limits of agreement -12.77 to 12.56ms], V2 QRS duration bias -0.09ms [-11.13 to
      10.96ms]; V1 TAD bias 0.14ms [-13.23 to 13.51ms], V2 TAD bias 0.008ms [-12.42 to
      12.44ms]. CONCLUSION: Comprehensive statistical evaluation of reproducibility of
      automated ECG measurements is important for appropriate interpretation of ECG.
      Automated ECG measurements are reproducible to within 25%.

PMID- 24883078
TI  - Simulation and evaluation of a high resolution VIP PEM system with a dedicated LM
      OSEM algorithm.
AB  - Over the last two decades there have been a growing number of designs for
      positron emission tomography (PET) cameras optimized to image the breast. These
      devices, commonly known as positron emission mammography (PEM) cameras allow much
      more spatial resolution by putting the photon detectors directly on the breast.
      PEM cameras have a compact geometry with a restricted field of view (FOV) thus
      exhibiting higher performance and lower cost than large whole body PET scanners.
      Typical PEM designs are based on scintillators such as bismuth germanate (BGO),
      lutetium oxorthosilicate (LSO) or lutetium yttrium orthosicilate (LYSO), and
      characterized by large parallax error due to deficiency of the depth of
      interaction (DOI) information from crystals. In the case of parallel geometry
      PEM, large parallax error results in poor image resolution along the vertical
      axis. In the framework of the Voxel Imaging PET (VIP) pathfinder project, we
      propose a high resolution PEM scanner based on pixelated solid-state CdTe
      detectors. The pixel PEM device with a millimeter-size pixel pitch provides an
      excellent spatial resolution in all directions 8 times better than standard
      commercial devices with a point spread function (PSF) of 1 mm full width at half
      maximum (FWHM) and excellent energy resolution of down to 1.6% FWHM at 511 keV
      photons at room temperature. The system is capable to detect down to 1 mm
      diameter hot spheres in warm background.

PMID- 24883081
TI  - PRISM: Fighting Against Open Access.

PMID- 24883082
TI  - EurocanPlatform, an FP7 project of the European Commission-first year commentary.

PMID- 24883080
TI  - Synthesis, characterization and evaluation of antioxidant activities of some
      novel chalcones analogues.
AB  - BACKGROUND: Chalcone, an important intermediate of flavonoid synthetic pathway,
      has been shown to exhibit diverse biological and pharmacological activities such
      as anti- cancer, antioxidant, anti-inflammatory, etc. RESULTS: In this study, a
      novel series of chalcones fatty acid esters 5b-e and 6b-e have been synthesized
      via the reaction of the respective chalcones with either palmitic or stearic
      acid. Another related class of compounds comprising 2,3-disubstituted chalcones
      7b-d and 8b(b')-d as well as 2-amino-6-(substituted-phenyl)-4-substitutedphenyl
      nicotinonitrile derivatives 9a,c,e have been also prepared by both electrophilic
      and Michael addition reactions, respectively, with the corresponding chalcones.
      The structures of all compounds are confirmed via a wide range of spectroscopic
      techniques including IR, (1)H and (13)C NMR, and mass spectra. Significantly, all
      synthesized compounds have been tested for their promising antioxidant activities
      via utilization of 1,1-biphenyl-2-picrylhydrazyl as a free radical scavenging
      reagent. Surprisingly, the results demonstrated that compound 5e (68.58% at C = 2
      MUg/ml) was more effective as an antioxidant agent than the ascorbic acid, a
      commonly used antioxidant. Furthermore, the role and contribution of different
      functional groups on the antioxidant activity of the synthesized chalcone
      derivatives are also probed and rationalized in terms of their electronic and
      structural effect. CONCLUSION: Good activity was noted for chalcone fatty acid
      esters, with some members recorded higher antioxidant activity than ascorbic
      acid.

PMID- 24883083
TI  - The cost of medical conferences.

PMID- 24883084
TI  - Brain metastases.

PMID- 24883079
TI  - Complicated intra-abdominal infections worldwide: the definitive data of the
      CIAOW Study.
AB  - The CIAOW study (Complicated intra-abdominal infections worldwide observational
      study) is a multicenter observational study underwent in 68 medical institutions
      worldwide during a six-month study period (October 2012-March 2013). The study
      included patients older than 18 years undergoing surgery or interventional
      drainage to address complicated intra-abdominal infections (IAIs). 1898 patients
      with a mean age of 51.6 years (range 18-99) were enrolled in the study. 777
      patients (41%) were women and 1,121 (59%) were men. Among these patients, 1,645
      (86.7%) were affected by community-acquired IAIs while the remaining 253 (13.3%)
      suffered from healthcare-associated infections. Intraperitoneal specimens were
      collected from 1,190 (62.7%) of the enrolled patients. 827 patients (43.6%) were
      affected by generalized peritonitis while 1071 (56.4%) suffered from localized
      peritonitis or abscesses. The overall mortality rate was 10.5% (199/1898).
      According to stepwise multivariate analysis (PR = 0.005 and PE = 0.001), several
      criteria were found to be independent variables predictive of mortality,
      including patient age (OR = 1.1; 95%CI = 1.0-1.1; p < 0.0001), the presence of
      small bowel perforation (OR = 2.8; 95%CI = 1.5-5.3; p < 0.0001), a delayed
      initial intervention (a delay exceeding 24 hours) (OR = 1.8; 95%CI = 1.5-3.7; p <
      0.0001), ICU admission (OR = 5.9; 95%CI = 3.6-9.5; p < 0.0001) and patient
      immunosuppression (OR = 3.8; 95%CI = 2.1-6.7; p < 0.0001). 

PMID- 24883085
TI  - The difficulties in cancer treatment.
AB  - Cancer is clearly the most deadly disease in the developed world as one in three
      people develop cancer during their lifetime. The cure for cancer is like the Holy
      Grail since most of the existing treatments are not effective enough to provide
      full protection from this disease. In recent years the burgeoning of
      sophisticated genomic, proteomic and bioinformatics techniques has made it
      possible for us to get a glimpse of the intricate interplay of numerous cellular
      genes and regulatory genetic elements that are responsible for the manifestation
      of cancerous phenotypes. With the use of modern genomic technologies we are now
      beginning to understand the enormous complexity of cancer. However there are few
      success stories as far as the treatment of cancer is concerned. For instance the
      treatments of leukemia and lymphoma have been established and proved to be
      satisfactory. Despite occasional successes the treatment for most cancers is
      still a long way from reality. In this editorial, we have addressed several
      reasons for the difficulties in cancer treatment. 

PMID- 24883086
TI  - What's wrong with early diagnosis of breast cancer in young women?

PMID- 24883087
TI  - Alternative metrics for measuring the quality of articles and journals.

PMID- 24883088
TI  - The AACR 2013 in Washington D.C.

PMID- 24883089
TI  - International Rare Cancers Initiative (IRCI).

PMID- 24883090
TI  - Meeting the current and future challenges of oncology drug development.
AB  - This breakout session highlighted four distinct perspectives from leading
      individuals within patient advocacy, industry, an appraisal committee and
      physicians on the future and challenges faced by targeted therapy in HTA
      evaluation. Bringing together leaders from key stakeholders in the process, it
      gave participants the opportunity to examine how the same HTA evaluation process
      is interpreted from multiple perspectives. The presentation of an industry
      supported "Six Nation Public Opinion Survey of Cancer Knowledge and Attitudes"
      provided detailed insight into how the general public, patients and caregivers
      view cancer alongside various available and possible future therapies. An
      interactive 'perspectives activity' session provided all participants with an
      opportunity to think through and discuss the HTA process, and its challenges,
      from the four distinct positions involved. We declare that we have no conflicts
      of interest. 

PMID- 24883091
TI  - Research for development and the role of 'grey literature' in southern African
      research production.

PMID- 24883092
TI  - Latin american symposium on oncological gastroenterology.

PMID- 24883093
TI  - Changing the paradigm in the cancer war: a strategy for the healthy and proper
      care of the sick.

PMID- 24883094
TI  - The world's first mobile lymphoedema unit: Wales leads the way.

PMID- 24883095
TI  - The role of heuristics and biases in cancer-related decisions.

PMID- 24883096
TI  - Powering cancer screening for overall mortality.

PMID- 24883097
TI  - Breast health day 2013.

PMID- 24883098
TI  - Quo vadis palliative care in Africa?

PMID- 24883099
TI  - "Small Journals", indexes and ecancer: an opportunity for Latin America.

PMID- 24883100
TI  - Improving care and reducing costs in oncology.

PMID- 24883101
TI  - Report on the 1st Indian cancer congress 2013.

PMID- 24883102
TI  - Superior triacylglycerol (TAG) accumulation in starchless mutants of Scenedesmus
      obliquus: (II) evaluation of TAG yield and productivity in controlled
      photobioreactors.
AB  - BACKGROUND: Many microalgae accumulate carbohydrates simultaneously with
      triacylglycerol (TAG) upon nitrogen starvation, and these products compete for
      photosynthetic products and metabolites from the central carbon metabolism. As
      shown for starchless mutants of the non-oleaginous model alga Chlamydomonas
      reinhardtii, reduced carbohydrate synthesis can enhance TAG production. However,
      these mutants still have a lower TAG productivity than wild-type oleaginous
      microalgae. Recently, several starchless mutants of the oleaginous microalga
      Scenedesmus obliquus were obtained which showed improved TAG content and
      productivity. RESULTS: The most promising mutant, slm1, is compared in detail to
      wild-type S. obliquus in controlled photobioreactors. In the slm1 mutant, the
      maximum TAG content increased to 57 +/- 0.2% of dry weight versus 45 +/- 1% in
      the wild type. In the wild type, TAG and starch were accumulated simultaneously
      during initial nitrogen starvation, and starch was subsequently degraded and
      likely converted into TAG. The starchless mutant did not produce starch and the
      liberated photosynthetic capacity was directed towards TAG synthesis. This
      increased the maximum yield of TAG on light by 51%, from 0.144 +/- 0.004 in the
      wild type to 0.217 +/- 0.011 g TAG/mol photon in the slm1 mutant. No differences
      in photosynthetic efficiency between the slm1 mutant and the wild type were
      observed, indicating that the mutation specifically altered carbon partitioning
      while leaving the photosynthetic capacity unaffected. CONCLUSIONS: The yield of
      TAG on light can be improved by 51% by using the slm1 starchless mutant of S.
      obliquus, and a similar improvement seems realistic for the areal productivity in
      outdoor cultivation. The photosynthetic performance is not negatively affected in
      the slm1 and the main difference with the wild type is an improved carbon
      partitioning towards TAG.

PMID- 24883103
TI  - Enhanced photo-fermentative H2 production using Rhodobacter sphaeroides by
      ethanol addition and analysis of soluble microbial products.
AB  - BACKGROUND: Biological fermentation routes can provide an environmentally
      friendly way of producing H2 since they use renewable biomass as feedstock and
      proceed under ambient temperature and pressure. In particular, photo-fermentation
      has superior properties in terms of achieving high H2 yield through complete
      degradation of substrates. However, long-term H2 production data with stable
      performance is limited, and this data is essential for practical applications. In
      the present work, continuous photo-fermentative H2 production from lactate was
      attempted using the purple non-sulfur bacterium, Rhodobacter sphaeroides KD131.
      As a gradual drop in H2 production was observed, we attempted to add ethanol
      (0.2% v/v) to the medium. RESULTS: As continuous operation went on, H2 production
      was not sustained and showed a negligible H2 yield (< 0.5 mol H2/mol
      lactateadded) within two weeks. Electron balance analysis showed that the reason
      for the gradual drop in H2 production was ascribed to the increase in production
      of soluble microbial products (SMPs). To see the possible effect of ethanol
      addition, a batch test was first conducted. The presence of ethanol significantly
      increased the H2 yield from 1.15 to 2.20 mol H2/mol lactateadded, by suppressing
      the production of SMPs. The analysis of SMPs by size exclusion chromatography
      showed that, in the later period of fermentation, more than half of the low
      molecular weight SMPs (< 1 kDa) were consumed and used for H2 production when
      ethanol had been added, while the concentration of SMPs continuously increased in
      the absence of ethanol. It was found that the addition of ethanol facilitated the
      utilization of reducing power, resulting in an increase in the cellular levels of
      NAD(+) and NADP(+). In continuous operation, ethanol addition was effective, such
      that stable H2 production was attained with an H2 yield of 2.5 mol H2/mol
      lactateadded. Less than 15% of substrate electrons were used for SMP production,
      whereas 35% were used in the control. CONCLUSIONS: We have found that SMPs are
      the key factor in photo-fermentative H2 production, and their production can be
      suppressed by ethanol addition. However, since external addition of ethanol to
      the medium represents an extra economic burden, ethanol should be prepared in a
      cost-effective way.

PMID- 24883104
TI  - Auditory stimulation with music influences the geometric indices of heart rate
      variability in men.
AB  - BACKGROUND: Chronic classical music was reported to increase parasympathetic
      activitywhen evaluating heart rate variability (HRV). It is poor in the
      literature investigation of the acute effects of baroque and heavy metal styles
      of musical auditory stimulation on HRV. In this study we evaluated the acute
      effects of relaxant baroque and excitatory heavy metal music on the geometric
      indices of HRV in healthy men. METHOD: The study was performed in 12 healthy men
      between 18 and 30 years old. We excluded persons with previous experience with
      music instrument and those who had affinity with the song styles. We analyzed the
      following indices: RRtri, TINN and Poincare plot (SD1, SD2 and SD1/SD2 ratio).
      HRV was recorded at rest for ten minutes. Subsequently they were exposed to
      relaxant baroque or excitatory heavy metal music for five minutes through an
      earphone. After the first music exposure they remained at rest for more five
      minutes and them they were exposed again to Baroque or Heavy Metal music (65-80
      dB). The sequence of songs was randomized for each individual. RESULTS: The RRTri
      and SD2 indices were reduced during the heavy metal musical auditory stimulation
      (p < 0.05). No changes were observed regarding TINN, SD1 and SD1/SD2 ratio (p >
      0.05).The qualitative Poincare plot analysis indicated that during relaxant
      classical baroque music there was observed a higher beat-to-beat dispersion of RR
      intervals compared with no music exposure and during excitatory heavy metal
      musical auditory stimulation, showing higher HRV. CONCLUSION: We suggest that
      excitatory heavy metal music acutely decreases global HRV.

PMID- 24883105
TI  - Pelvic floor muscle rehabilitation for patients with lifelong premature
      ejaculation: a novel therapeutic approach.
AB  - OBJECTIVES: Premature ejaculation is the most common male sexual disorder. The
      aim of the study was to evaluate the possible therapeutic role of pelvic floor
      muscle rehabilitation in patients affected by lifelong premature ejaculation.
      METHODS: We treated 40 men with lifelong premature ejaculation, reporting, a
      baseline intravaginal ejaculatory latency time (IELT) <= 1 min, with 12-week
      pelvic floor muscle rehabilitation. RESULTS: At the end of the rehabilitation,
      mean IELTs were calculated to evaluate the effectiveness of the therapy. At the
      end of the treatment, 33 (82.5%) of the 40 patients gained control of their
      ejaculatory reflex, with a mean IELT of 146.2 s (range: 123.6-152.4 s). A total
      of 13 out of 33 (39%) patients were evaluated at 6 months follow up, and they
      maintained a significant IELT (112.6 s) compared with their initial IELT (mean
      39.8 s). CONCLUSIONS: The results obtained in our subjects treated with pelvic
      floor rehabilitation are promising. This therapy represents an important cost
      reduction compared with the standard treatment (selective serotonin reuptake
      inhibitors). Based on the present data, we propose pelvic floor muscle
      rehabilitation as a new, viable therapeutic option for the treatment of premature
      ejaculation.

PMID- 24883106
TI  - A green and black tea extract benefits urological health in men with lower
      urinary tract symptoms.
AB  - OBJECTIVES: The objective of this study was to examine the effects of a green and
      black tea extract blend [AssuriTEA Men's Health (AMH)] in men with lower urinary
      tract symptoms (LUTS). METHODS: In this randomized, double-blind, placebo
      controlled study, 46 men aged 30-70 with an American Urologic Association symptom
      score (AUAss) of at least 8 and up to 24 were randomized to 500 mg AMH, 1000 mg
      AMH, or placebo daily for 12 weeks. Measurements were taken at baseline (BL),
      week 6 and week 12 for AUAss, simple uroflowmetry, postvoid residual volume
      (PVR), C-reactive protein (CRP), Short-Form 36 Health Survey (SF-36), and
      International Index of Erectile Function (IIEF). RESULTS: A total of 40 subjects
      completed the study. AUAss decreased 34.5% from BL to week 12 in the 1000 mg AMH
      group (p = 0.008). At week 12, CRP increased in the 500 mg AMH (p = 0.003) and
      placebo (p = 0.012) groups from their BL levels but not in the 1000 mg group.
      Average urine flow (Qmean) increased in the 500 mg (p = 0.033) and 1000 mg AMH (p
      = 0.002) groups versus placebo. PVR decreased in the 1000 mg AMH group (p =
      0.034) from BL at week 6. Treatment group effects were observed for the physical
      functioning and sexual desire domains of the SF-36 and IIEF (p = 0.051 and p =
      0.005 respectively). AMH was well tolerated. CONCLUSIONS: Oral administration of
      AMH improved LUTS and quality of life in as little as 6 weeks.

PMID- 24883107
TI  - The role of cabazitaxel in the treatment of metastatic castration-resistant
      prostate cancer.
AB  - For decades, cytotoxic therapy was considered ineffective for the treatment of
      metastatic castration-resistant prostate cancer (mCRPC). Earlier therapies such
      as estramustine and mitoxantrone received regulatory approval based upon
      improvement in palliative endpoints. In 2004, docetaxel became the first
      treatment to demonstrate a significant survival benefit in patients with mCRPC
      based on two randomized phase III studies, TAX327 and SWOG 99-16. Cabazitaxel, a
      third-generation taxane, was chosen for clinical development based on its
      decreased affinity for the drug efflux pump, p-glycoprotein, which is a frequent
      cause of drug resistance in docetaxel-resistant preclinical models. In 2010,
      cabazitaxel was approved by the US Food and Drug Administration as the first
      therapy to show a survival benefit for the treatment of patients with docetaxel
      refractory mCRPC. This review summarizes the existing literature on the use of
      cabazitaxel, focusing on its efficacy and safety in combination with prednisone
      in the treatment of mCRPC, as well as its role in an era of new therapeutic
      options. 

PMID- 24883108
TI  - Pharmacological treatment of chronic pelvic ischemia.
AB  - Epidemiological studies have shown that lower urinary tract symptoms, including
      overactive bladder, commonly occur in both men and women, with an age-related
      increase in both sexes. Vascular endothelial dysfunction and urological symptoms
      are common in the metabolic syndrome; they also occur during the human ageing
      process and are independent risk factors for the development of atherosclerosis
      and hypertension. Pelvic arterial insufficiency may lead to impaired lower
      urinary tract perfusion and play an important role in the development of bladder
      dysfunction such as detrusor overactivity and overactive bladder. It seems
      reasonable, but has not been definitely established clinically, that chronic
      ischemia-related bladder dysfunction will progress to bladder underactivity.
      Studies in experimental models in rabbits and rats have shown that pelvic
      arterial insufficiency may result in significant bladder ischemia with reduced
      bladder wall oxygen tension, oxidative stress, increased muscarinic receptor
      activity, ultrastructural damage, and neurodegeneration. Several types of drug
      may be able to prevent some of these changes. Even if the alpha1-adrenoceptor
      blocker, silodosin, the phosphodiesterase type 5 inhibitor, tadalafil, the beta3
      alpha1-adrenoceptor agonist, mirabegron, and the free radical scavenger,
      melatonin, were unable to prevent the development of neointimal hyperplasia and
      consequent luminal occlusion in animal models, they all exerted a protecting
      effect on urodynamic parameters, and on the functional and morphological changes
      of the bladder demonstrable in vitro. The different mechanisms of action of the
      drugs suggest that many factors are involved in the pathogenesis of chronic
      ischemia-induced bladder dysfunction and can be targets for intervention. Since
      several of the agents tested are used clinically and effectively for relieving
      lower urinary tract symptoms, the results from animal models of chronic bladder
      ischemia seem to have translational value. Animal models may be of relevance for
      designing clinical studies to demonstrate if a certain drug may prevent
      progression of ischemia-related functional and morphological bladder changes. 

PMID- 24883109
TI  - Management of iatrogenic ureteral injury.
AB  - Iatrogenic injury to the ureter is a potentially devastating complication of
      modern surgery. The ureters are most often injured in gynecologic, colorectal,
      and vascular pelvic surgery. There is also potential for considerable ureteral
      injury during endoscopic procedures for ureteric pathology such as tumor or
      lithiasis. While maneuvers such as perioperative stenting have been touted as a
      means to avoid ureteral injury, these techniques have not been adopted
      universally, and the available literature does not make a case for their routine
      use. Distal ureteral injuries are best managed with ureteroneocystostomy with or
      without a vesico-psoas hitch. Mid-ureteral and proximal ureteral injuries can
      potentially be managed with ureteroureterostomy. If the distal segment is
      unsuitable for anastomosis then a number of techniques are available for repair
      including a Boari tubularized bladder flap, transureteroureterostomy, or renal
      autotransplantation. In rare cases renal autotransplantation or ureteral
      substitution with gastrointestinal segments may be warranted to re-establish
      urinary tract continuity. Laparoscopic and minimally invasive techniques have
      been employed to remedy iatrogenic ureteral injuries. 

PMID- 24883110
TI  - Radiographic imaging for traumatic ankle injuries: a demand profile and
      investigation of radiological reporting timeframes from an Australian tertiary
      facility.
AB  - BACKGROUND: Radiographic examinations of the ankle are important in the clinical
      management of ankle injuries in hospital emergency departments. National
      (Australian) Emergency Access Targets (NEAT) stipulate that 90 percent of
      presentations should leave the emergency department within 4 hours. For a
      radiological report to have clinical usefulness and relevance to clinical teams
      treating patients with ankle injuries in emergency departments, the report would
      need to be prepared and available to the clinical team within the NEAT 4 hour
      timeframe; before the patient has left the emergency department. However, little
      is known about the demand profile of ankle injuries requiring radiographic
      examination or time until radiological reports are available for this clinical
      group in Australian public hospital emergency settings. METHODS: This study
      utilised a prospective cohort of consecutive cases of ankle examinations from
      patients (n = 437) with suspected traumatic ankle injuries presenting to the
      emergency department of a tertiary hospital facility. Time stamps from the
      hospital Picture Archiving and Communication System were used to record the
      timing of three processing milestones for each patient's radiographic
      examination; the time of image acquisition, time of a provisional radiological
      report being made available for viewing by referring clinical teams, and time of
      final verification of radiological report. RESULTS: Radiological reports and all
      three time stamps were available for 431 (98.6%) cases and were included in
      analysis. The total time between image acquisition and final radiological report
      verification exceeded 4 hours for 404 (92.5%) cases. The peak demand for
      radiographic examination of ankles was on weekend days, and in the afternoon and
      evening. The majority of examinations were provisionally reported and verified
      during weekday daytime shift hours. CONCLUSIONS: Provisional or final
      radiological reports were frequently not available within 4 hours of image
      acquisition among this sample. Effective and cost-efficient strategies to improve
      the support provided to referring clinical teams from medical imaging departments
      may enhance emergency care interventions for people presenting to emergency
      departments with ankle injuries; particularly those with imaging findings that
      may be challenging for junior clinical staff to interpret without a definitive
      radiological report.

PMID- 24883112
TI  - The impact of serine protease HtrA in apoptosis, intestinal immune responses and
      extra-intestinal histopathology during Campylobacter jejuni infection of infant
      mice.
AB  - BACKGROUND: Campylobacter jejuni has emerged as a leading cause of bacterial
      enterocolitis. The serine protease HtrA has been shown to be a pivotal, novel C.
      jejuni virulence factor involved in cell invasion and transmigration across
      polarised epithelial cells in vitro. However, the functional relevance of the
      htrA gene for the interaction of C. jejuni with the host immune system in the
      infant mouse infection model has not been investigated so far. RESULTS: Here we
      studied the role of C. jejuni htrA during infection of 3-weeks-old infant mice.
      Immediately after weaning, conventional wild-type mice were perorally infected
      with the NCTC11168?htrA mutant (?htrA) or the parental wild-type strain.
      Approximately one third of infected infant mice suffered from bloody diarrhea
      until day 7 post infection (p.i.), whereas colonic histopathological changes were
      rather moderate but comparable between the two strains. Interestingly, parental,
      but not ?htrA mutant infected mice, displayed a multifold increase of apoptotic
      cells in the colonic mucosa at day 7 p.i., which was paralleled by higher colonic
      levels of pro-inflammatory cytokines such as TNF-alpha and IFN-gamma and the
      matrix-degrading enzyme matrixmetalloproteinase-2 (MMP-2). Furthermore, higher
      numbers of proliferating cells could be observed in the colon of ?htrA infected
      mice as compared to the parental wild-type strain. Remarkably, as early as 7 days
      p.i. infant mice also exhibited inflammatory changes in extra-intestinal
      compartments such as liver, kidneys and lungs, which were less distinct in
      kidneys and lungs following ?htrA versus parental strain infection. However, live
      C. jejuni bacteria could not be found in these organs, suggesting the induction
      of systemic effects during intestinal infection. CONCLUSION: Upon C. jejuni ?htrA
      strain infection of infant mice, intestinal and extra-intestinal pro-inflammatory
      immune responses were ameliorated in the infant mouse model system. Future
      studies will shed further light onto the molecular mechanisms of host-pathogen
      interactions.

PMID- 24883114
TI  - Condorcet and borda count fusion method for ligand-based virtual screening.
AB  - BACKGROUND: It is known that any individual similarity measure will not always
      give the best recall of active molecule structure for all types of activity
      classes. Recently, the effectiveness of ligand-based virtual screening approaches
      can be enhanced by using data fusion. Data fusion can be implemented using two
      different approaches: group fusion and similarity fusion. Similarity fusion
      involves searching using multiple similarity measures. The similarity scores, or
      ranking, for each similarity measure are combined to obtain the final ranking of
      the compounds in the database. RESULTS: The Condorcet fusion method was examined.
      This approach combines the outputs of similarity searches from eleven association
      and distance similarity coefficients, and then the winner measure for each class
      of molecules, based on Condorcet fusion, was chosen to be the best method of
      searching. The recall of retrieved active molecules at top 5% and significant
      test are used to evaluate our proposed method. The MDL drug data report (MDDR),
      maximum unbiased validation (MUV) and Directory of Useful Decoys (DUD) data sets
      were used for experiments and were represented by 2D fingerprints. CONCLUSIONS:
      Simulated virtual screening experiments with the standard two data sets show that
      the use of Condorcet fusion provides a very simple way of improving the ligand
      based virtual screening, especially when the active molecules being sought have a
      lowest degree of structural heterogeneity. However, the effectiveness of the
      Condorcet fusion was increased slightly when structural sets of high diversity
      activities were being sought.

PMID- 24883111
TI  - "Platelet-associated regulatory system (PARS)" with particular reference to
      female reproduction.
AB  - BACKGROUND: Blood platelets play an essential role in hemostasis, thrombosis and
      coagulation of blood. Beyond these classic functions their involvement in
      inflammatory, neoplastic and immune processes was also investigated. It is well
      known, that platelets have an armament of soluble molecules, factors, mediators,
      chemokines, cytokines and neurotransmitters in their granules, and have multiple
      adhesion molecules and receptors on their surface. METHODS: Selected relevant
      literature and own views and experiences as clinical observations have been used.
      RESULTS: Considering that platelets are indispensable in numerous homeostatic
      endocrine functions, it is reasonable to suppose that a platelet-associated
      regulatory system (PARS) may exist; internal or external triggers and/or stimuli
      may complement and connect regulatory pathways aimed towards target tissues
      and/or cells. The signal (PAF, or other tissue/cell specific factors) comes from
      the stimulated (by the e.g., hypophyseal hormones, bacteria, external factors,
      etc.) organs or cells, and activates platelets. Platelet activation means their
      aggregation, sludge formation, furthermore the release of the for-mentioned
      biologically very powerful factors, which can locally amplify and deepen the
      tissue specific cell reactions. If this process is impaired or inhibited for any
      reason, the specifically stimulated organ shows hypofunction. When PARS is
      upregulated, organ hyperfunction may occur that culminate in severe diseases.
      CONCLUSION: Based on clinical and experimental evidences we propose that
      platelets modulate the function of hypothalamo-hypophyseal-ovarian system.
      Specifically, hypothalamic GnRH releases FSH from the anterior pituitary, which
      induces and stimulates follicular and oocyte maturation and steroid hormone
      secretion in the ovary. At the same time follicular cells enhance PAF production.
      Through these pathways activated platelets are accumulated in the follicular
      vessels surrounding the follicle and due to its released soluble molecules
      (factors, mediators, chemokines, cytokines, neurotransmitters) locally increase
      oocyte maturation and hormone secretion. Therefore we suggest that platelets are
      not only a small participant but may be the conductor or active mediator of this
      complex regulatory system which has several unrevealed mechanisms. In other words
      platelets are corpuscular messengers, or are more than a member of the family
      providing hemostasis.

PMID- 24883113
TI  - Update on the pathogenic potential and treatment options for Blastocystis sp.
AB  - Although Blastocystis is one of the most common enteric parasites, there is still
      much controversy surrounding the pathogenicity and potential treatment options
      for this parasite. In this review we look at the evidence supporting Blastocystis
      as an intestinal pathogen as shown by numerous case studies and several in vivo
      studies and the evidence against. We describe the chronic nature of some
      infections and show the role of Blastocystis in immunocompromised patients and
      the relationship between irritable bowel syndrome and Blastocystis infection.
      There have been several studies that have suggested that pathogenicity may be
      subtype related. Metronidazole is the most widely accepted treatment for
      Blastocystis but several cases of treatment failure and resistance have been
      described. Other treatment options which have been suggested include paromomycin
      and trimethroprim- sulfamethoxazole. 

PMID- 24883115
TI  - Increased serum C1q-binding adiponectin complex to total-adiponectin ratio in men
      with multi-vessel coronary disease.
AB  - BACKGROUND: Adiponectin plays a role as a positive contributor to the
      stabilization of atherosclerotic plaques. Circulating total adiponectin (Total
      APN) levels associates with the number of coronary vessels in men with coronary
      artery disease (CAD). We recently reported that adiponectin binds to C1q in human
      blood, and serum C1q-binding adiponectin (C1q-APN) /Total-APN levels are
      associated with CAD in type 2 diabetic subjects. The present study investigated
      the relationship between circulating C1q-APN levels and the number of
      angiographic coronary artery vessel in male subjects. METHODS: The study subjects
      were 53 male Japanese patients who underwent diagnostic coronary angiography.
      Blood total adiponectin (Total-APN), high-molecular weight adiponectin (HMW-APN),
      C1q-APN and C1q were measured by enzyme-linked immunosorbent assays. RESULTS:
      Serum C1q-APN/Total-APN ratio significantly increased in subjects with single and
      multi-vessel coronary diseases (p = 0.029 for trend, the Kruskal-Wallis test).
      However, serum Total-APN, HMW-APN, C1q-APN and C1q levels did not correlate with
      number of diseased coronary vessels. CONCLUSION: Serum C1q-APN/Total-APN ratio
      progressively increases in men with single and multi-vessel coronary disease.
      TRIAL REGISTRATION: UMIN000002997.

PMID- 24883116
TI  - Autocatalytic sets in a partitioned biochemical network.
AB  - BACKGROUND: In previous work, RAF theory has been developed as a tool for making
      theoretical progress on the origin of life question, providing insight into the
      structure and occurrence of self-sustaining and collectively autocatalytic sets
      within catalytic polymer networks. We present here an extension in which there
      are two "independent" polymer sets, where catalysis occurs within and between the
      sets, but there are no reactions combining polymers from both sets. Such an
      extension reflects the interaction between nucleic acids and peptides observed in
      modern cells and proposed forms of early life. RESULTS: We present theoretical
      work and simulations which suggest that the occurrence of autocatalytic sets is
      robust to the partitioned structure of the network. We also show that
      autocatalytic sets remain likely even when the molecules in the system are not
      polymers, and a low level of inhibition is present. Finally, we present a kinetic
      extension which assigns a rate to each reaction in the system, and show that
      identifying autocatalytic sets within such a system is an NP-complete problem.
      CONCLUSIONS: Recent experimental work has challenged the necessity of an RNA
      world by suggesting that peptide-nucleic acid interactions occurred early in
      chemical evolution. The present work indicates that such a peptide-RNA world
      could support the spontaneous development of autocatalytic sets and is thus a
      feasible alternative worthy of investigation.

PMID- 24883117
TI  - Serial transfer can aid the evolution of autocatalytic sets.
AB  - BACKGROUND: The concept of an autocatalytic set of molecules has been posited
      theoretically and demonstrated empirically with catalytic RNA molecules. For this
      concept to have significance in a realistic origins-of-life scenario, it will be
      important to demonstrate the evolvability of such sets. Here, we employ a
      Gillespie algorithm to improve and expand on previous simulations of an empirical
      system of self-assembling RNA fragments that has the ability to spontaneously
      form autocatalytic networks. We specifically examine the role of serial transfer
      as a plausible means to allow time-dependent changes in set composition, and
      compare the results to equilibrium, or "batch" scenarios. RESULTS: We show that
      the simulation model produces results that are in close agreement with the
      original experimental observations in terms of generating varying autocatalytic
      (sub)sets over time. Furthermore, the model results indicate that in a "batch"
      scenario the equilibrium distribution is largely determined by competition for
      resources and stochastic fluctuations. However, with serial transfer the system
      is prevented from reaching such an equilibrium state, and the dynamics are mostly
      determined by differences in reaction rates. This is a consistent pattern that
      can be repeated, or made stronger or weaker by varying the reaction rates or the
      duration of the transfer steps. Increasing the number of molecules in the
      simulation actually strengthens the potential for selection. CONCLUSIONS: These
      simulations provide a more realistic emulation of wet lab conditions using self
      assembling catalytic RNAs that form interaction networks. In doing so, they
      highlight the potential evolutionary advantage to a prebiotic scenario that
      involves cyclic dehydration/rehydration events. We posit that such cyclicity is a
      plausible means to promote evolution in primordial autocatalytic sets, which
      could later lead to the establishment of individual-based biology.

PMID- 24883118
TI  - Mesoporous magnetic gold "nanoclusters" as theranostic carrier for chemo
      photothermal co-therapy of breast cancer.
AB  - Photothermal therapy (PTT) is proved to be an efficient manner for superficial
      tumor therapy in preclinical studying. The tumor suppression of chemotherapy can
      be enhanced by combining with PTT. In this study, we reported a mesoporous
      magnetic gold "nanoclusters" (MMGNCs) structure as theranostic carrier for chemo
      photothermal co-therapy. MMGNCs were successfully prepared and they exhibited
      efficient photo-thermal effect for PTT. The mesoporous structure provided MMGNCs
      with high drug loading capacity. By in vitro cytotoxicity testing, we revealed
      that the combination of PTT and chemotherapy could cause more damage than
      chemotherapy or PTT did alone. By topically targeting mediated by the extra
      magnetic field (MF), MMGNCs can be targeted to the tumor site efficiently. In
      vivo chemo-photothermal co-therapy of 4T1 breast cancer, under the combinational
      treatments of chemo-photothermal co-therapy and extra-MF targeting, the tumor
      growth has been efficiently inhibited, and the pulmonary and mediastinal
      metastasis have also been prevented. The survival of the cancer bearing mice was
      prolonged. The bio-imaging applications of this system and the mechanism of the
      metastasis prevention are ongoing. 

PMID- 24883119
TI  - Simultaneous mapping of pan and sentinel lymph nodes for real-time image-guided
      surgery.
AB  - The resection of regional lymph nodes in the basin of a primary tumor is of
      paramount importance in surgical oncology. Although sentinel lymph node mapping
      is now the standard of care in breast cancer and melanoma, over 20% of patients
      require a completion lymphadenectomy. Yet, there is currently no technology
      available that can image all lymph nodes in the body in real time, or assess both
      the sentinel node and all nodes simultaneously. In this study, we report an
      optical fluorescence technology that is capable of simultaneous mapping of pan
      lymph nodes (PLNs) and sentinel lymph nodes (SLNs) in the same subject. We
      developed near-infrared fluorophores, which have fluorescence emission maxima
      either at 700 nm or at 800 nm. One was injected intravenously for identification
      of all regional lymph nodes in a basin, and the other was injected locally for
      identification of the SLN. Using the dual-channel FLARE intraoperative imaging
      system, we could identify and resect all PLNs and SLNs simultaneously. The
      technology we describe enables simultaneous, real-time visualization of both PLNs
      and SLNs in the same subject. 

PMID- 24883120
TI  - A new method to assay protease based on amyloid misfolding: application to
      prostate cancer diagnosis using a panel of proteases biomarkers.
AB  - This paper reports a sensitive method with electrochemical technique to detect
      various proteases, which can be used for the diagnosis of prostate cancer. For
      the proposed assay method, the working electrode is modified with the peptide
      probes for the target proteases. These probes contain the substrate sequence of
      target proteases, as well as the seed peptide sequence that can accelerate the
      misfolding of amyloid-beta. If there are proteases in the test solution, after
      protease cleavage of the substrate peptides, the distal seed peptide will be
      removed from the electrode surface. So, in the absence of proteases, the seed
      peptides can initiate and accelerate amyloid-beta misfolding on the electrode
      surface. Consequently, the formed aggregates strongly block the electron transfer
      of the in-solution electroactive species with the electrode, resulting in
      suppressed signal readout. Nevertheless, in the presence of proteases, enzyme
      cleavage may lead to greatly mitigated protein misfolding and evident signal
      enhancement. Since the contrast in signal readout between the two cases can be
      amplified by using the protein misfolding step, high sensitivity suitable for
      direct detection of proteases in serum can be achieved. These results may suggest
      the feasibility of our new method for the detection of a panel of proteases in
      offering detailed diagnosis of prostate cancer and a better treatment of the
      cancer. 

PMID- 24883121
TI  - Targeted radionuclide therapy with A 177Lu-labeled anti-HER2 nanobody.
AB  - RIT has become an attractive strategy in cancer treatment, but still faces
      important drawbacks due to poor tumor penetration and undesirable
      pharmacokinetics of the targeting vehicles. Smaller radiolabeled antibody
      fragments and peptides feature highly specific target accumulation, resulting in
      low accumulation in healthy tissue, except for the kidneys. Nanobodies are the
      smallest (MW<15 kDa) functional antigen-binding fragments that are derived from
      heavy chain-only camelid antibodies. Here, we show that the extend of kidney
      retention of nanobodies is predominantly dictated by the number of polar residues
      in the C-terminal amino acid tag. Three nanobodies were produced with different C
      terminal amino-acid tag sequences (Myc-His-tagged, His-tagged, and untagged).
      Dynamic planar imaging of Wistar rats with 111In-DTPA-nanobodies revealed that
      untagged nanobodies showed a 70% drop in kidney accumulation compared to Myc-His
      tagged nanobodies at 50 min p.i.. In addition, coinfusion of untagged nanobodies
      with the plasma expander Gelofusin led to a final reduction of 90%. Similar
      findings were obtained with different 177Lu-DTPA-2Rs15d nanobody constructs in
      HER2pos tumor xenografted mice at 1 h p.i.. Kidney accumulation decreased 88%
      when comparing Myc-His-tagged to untagged 2Rs15d nanobody, and 95% with a
      coinfusion of Gelofusin, without affecting the tumor targeting capacity.
      Consequently, we identified a generic method to reduce kidney retention of
      radiolabeled nanobodies. Dosimetry calculations of Gelofusin-coinfused, untagged
      177Lu-DTPA-2Rs15d revealed a dose of 0.90 Gy/MBq that was delivered to both tumor
      and kidneys and extremely low doses to healthy tissues. In a comparative study,
      177Lu-DTPA-Trastuzumab supplied 6 times more radiation to the tumor than untagged
      177Lu-DTPA-2Rs15d, but concomitantly also a 155, 34, 80, 26 and 4180 fold higher
      radioactivity burden to lung, liver, spleen, bone and blood. Most importantly,
      nanobody-based targeted radionuclide therapy in mice bearing small estiblashed
      HER2pos tumors led to an almost complete blockade of tumor growth and a
      significant difference in event-free survival between the treated and the control
      groups (P<0.0001). Based on histology analyses, no evidence of renal
      inflammation, apoptosis or necrosis was obtained. In conclusion, these data
      highlight the importance of the amino acid composition of the nanobody's C
      terminus, as it has a predominant effect on kidney retention. Moreover, we show
      successful nanobody-based targeted radionuclide therapy in a xenograft model and
      highlight the potential of radiolabeled nanobodies as a valuable adjuvant therapy
      candidate for treatment of minimal residual and metastatic disease.

PMID- 24883125
TI  - Malaria theranostics using hemozoin-generated vapor nanobubbles.
AB  - Malaria remains a widespread and deadly infectious human disease, with increasing
      diagnostic and therapeutic challenges due to the drug resistance and
      aggressiveness of malaria infection. Early detection and innovative approaches
      for parasite destruction are needed. The high optical absorbance and nano-size of
      hemozoin crystals have been exploited to detect and mechanically destroy the
      malaria parasite in a single theranostic procedure. Transient vapor nanobubbles
      are generated around hemozoin crystals in malaria parasites in infected
      erythrocytes in response to a single short laser pulse. Optical scattering
      signals of the nanobubble report the presence of the malaria parasite. The
      mechanical impact of the same nanobubble physically destroys the parasite in
      nanoseconds in a drug-free manner. Laser-induced nanobubble treatment of human
      blood in vitro results in destruction of up to 95% of parasites after a single
      procedure, and delivers an 8-fold better parasiticidal efficacy compared to
      standard chloroquine drug treatment. The mechanism of destruction is highly
      selective for malaria infected red cells and does not harm neighboring,
      uninfected erythrocytes. Thus, laser pulse-induced vapor nanobubble generation
      around hemozoin supports both rapid and highly specific detection and destruction
      of malaria parasites in one theranostic procedure. 

PMID- 24883124
TI  - Dimerization of a phage-display selected peptide for imaging of alphavbeta6-
      integrin: two approaches to the multivalent effect.
AB  - The integrin alphavbeta6 is an emerging biomarker for non-small cell lung cancer
      (NSCLC). An alphavbeta6-binding peptide was previously selected from a phage
      displayed peptide library. Here, we utilize a multivalent design to develop a
      peptidic probe for positron emission tomography (PET) imaging of alphavbeta6+
      NSCLC tumors. Multimeric presentation of this peptide, RGDLATLRQL, on a
      bifunctional copper chelator was achieved using two approaches: dimerization of
      the peptide followed by conjugation to the chelator (H2-D10) and direct
      presentation of two copies of the peptide on the chelator scaffold (H2-(M10)2).
      Binding affinities of the divalent peptide conjugates are four-fold higher than
      their monovalent counterpart (H2-M10), suggestive of multivalent binding. PET
      imaging using the bivalent 64Cu-labeled conjugates showed rapid and persistent
      accumulation in alphavbeta6+ tumors. By contrast, no significant accumulation was
      observed in alphavbeta6- tumors. Irrespective of the dimerization approach, all
      divalent probes showed three-fold higher tumor uptake than the monovalent probe,
      indicating the role of valency in signal enhancement. However, the divalent
      probes have elevated uptake in non-target organs, especially the kidneys. To
      abrogate nonspecific uptake, the peptide's N-terminus was acetylated. The
      resultant bivalent probe, 64Cu- AcD10, showed drastic decrease of kidney
      accumulation while maintaining tumor uptake. In conclusion, we developed an
      alphavbeta6-integrin specific probe with optimized biodistribution for
      noninvasive PET imaging of NSCLC. Further, we have demonstrated that use of
      multivalent scaffolds is a plausible method to improve library selected peptides,
      which would be suboptimal or useless otherwise, for imaging probe development.

PMID- 24883126
TI  - Epigenetic Mechanism in Regulation of Endothelial Function by Disturbed Flow:
      Induction of DNA Hypermethylation by DNMT1.
AB  - There is increasing evidence that epigenetic mechanisms such as changes in DNA
      methylation and histone modification play an important role in regulating
      cellular functions in physiological and pathophysiological states. We
      investigated the effects of hemodynamic force disturbance, one of the risk
      factors for atherogenesis, on DNA methylation in HUVECs and rat carotid arteries.
      Our results demonstrated that athero-prone oscillatory shear flow (OS) without a
      clear direction induces DNA hypermethylation in comparison to the athero
      protective pulsatile shear flow (PS) with a definite direction. Furthermore, OS
      increases the expression and nuclear translocation of DNA methyltransferase 1
      (DNMT1), which is a major maintenance DNA methyltransferase that adds methyl
      groups to hemi-methylated DNA to repress gene expression. Pharmacological
      inhibition of DNMT1 by 5-Aza-2'-deoxycytidine abolished the OS-induced DNA
      hypermethylation. In vivo experiments also showed increases of DNMT1 expression
      and DNA methylation in the partially-ligated rat carotid arteries where the shear
      flow is disturbed. These in vitro and in vivo findings have provided novel
      evidence of the differential regulation of DNA methylation by different
      hemodynamic forces acting on vascular endothelium and identified DNMT1 as a key
      protein that governs the epigenetic changes in response to the pathophysiological
      stimuli due to disturbed flow.

PMID- 24883123
TI  - The prognostic value of 18F-FDG PET/CT for hepatocellular carcinoma treated with
      transarterial chemoembolization (TACE).
AB  - 18F-Fluoro-deoxyglucose (FDG) PET/CT can be used to monitor the biological
      behavior of hepatocellular carcinoma (HCC). Baseline PET/CT has prognostic value
      in HCC patients, but there is litter knowledge of the PET/CT changes after
      treatment. We evaluated 27 HCC patients treated with transarterial
      chemoembolization (TACE) from June 2011 to July 2012, and we investigated the
      prognostic value of PET/CT. Patients were followed up with regular clinical and
      laboratory examinations and contrast-enhanced spiral computed tomography (CT).
      Furthermore, PET/CT assessments were collected and analyzed before (range 1~15 d)
      and after the first month of TACE (range, 27~45 d). We tested the prognostic
      value of the tumor standardized uptake value (TSUV) and normal liver SUV(LSUV)
      according to the VOI (volume of interest). The SUVs were used to assess the
      relationship between the treatment response and survival. To assess their
      prognostic value, we evaluated the areas under the receiver operating
      characteristic (ROC) curves of different SUVs for predicting survival. Finally,
      the median overall survival (OS) and time to progression (TTP) for 27 patients
      were 15.4 months (95%CI, 3.3-27.5 months) and 11.4 months (95%CI, 6.7-16.1
      months), respectively. The DeltaTSUVmax%, based on the VOI, had the highest
      discriminative prognostic value and the cutoff PET/CT response was 0.1 with a
      sensitivity of 100% and a specificity of 95.2%. The OS was significantly better
      in the PET/CT response group than in the PET/CT non-response group (p=0.025). In
      conclusion, an early interim PET/CT after TACE may have prognostic value for HCC
      patients treated with TACE, and the DeltaTSUVmax% may help in determining the
      HCCs viability in patients with high baseline and follow-up18F-FDG uptake.

PMID- 24883122
TI  - Luminescent dual sensors reveal extracellular pH-gradients and hypoxia on chronic
      wounds that disrupt epidermal repair.
AB  - Wound repair is a quiescent mechanism to restore barriers in multicellular
      organisms upon injury. In chronic wounds, however, this program prematurely
      stalls. It is known that patterns of extracellular signals within the wound fluid
      are crucial to healing. Extracellular pH (pHe) is precisely regulated and
      potentially important in signaling within wounds due to its diverse cellular
      effects. Additionally, sufficient oxygenation is a prerequisite for cell
      proliferation and protein synthesis during tissue repair. It was, however,
      impossible to study these parameters in vivo due to the lack of imaging tools.
      Here, we present luminescent biocompatible sensor foils for dual imaging of pHe
      and oxygenation in vivo. To visualize pHe and oxygen, we used time-domain dual
      lifetime referencing (tdDLR) and luminescence lifetime imaging (LLI),
      respectively. With these dual sensors, we discovered centripetally increasing pHe
      gradients on human chronic wound surfaces. In a therapeutic approach, we identify
      pHe-gradients as pivotal governors of cell proliferation and migration, and show
      that these pHe-gradients disrupt epidermal barrier repair, thus wound closure.
      Parallel oxygen imaging also revealed marked hypoxia, albeit with no correlating
      oxygen partial pressure (pO2)-gradient. This highlights the distinct role of pHe
      gradients in perturbed healing. We also found that pHe-gradients on chronic
      wounds of humans are predominantly generated via centrifugally increasing pHe
      regulatory Na+/H+-exchanger-1 (NHE1)-expression. We show that the modification of
      pHe on chronic wound surfaces poses a promising strategy to improve healing. The
      study has broad implications for cell science where spatial pHe-variations play
      key roles, e.g. in tumor growth. Furthermore, the novel dual sensors presented
      herein can be used to visualize pHe and oxygenation in various biomedical fields.

PMID- 24883127
TI  - Development of a method to quantify platelet adhesion and aggregation under
      static conditions.
AB  - Platelets are important players in hemostasis and thrombosis. Thus, accurate
      assessment of platelet function is crucial for identifying platelet function
      disorders and measuring the efficacy of antiplatelet therapies. We have developed
      a novel platelet aggregation technique that utilizes the physical parameter of
      platelet concentration in conjunction with volume and mass measurements to
      evaluate platelet adhesion and aggregation. Platelet aggregates were formed by
      incubating purified platelets on fibrinogen- or fibrillar collagen-coated
      surfaces at platelet concentrations ranging from 20,000 to 500,000 platelets/ L.
      Platelets formed aggregates under static conditions in a platelet concentration
      dependent manner, with significantly greater mean volume and mass at higher
      platelet concentrations ( 400,000 platelets/ L). We show that a platelet
      glycoprotein IIb/IIIa inhibitor abrogated platelet-platelet aggregation, which
      significantly reduced the volume and mass of the platelets on the collagen
      surface. This static platelet aggregation technique is amenable to
      standardization and represents a useful tool to investigate the mechanism of
      platelet activation and aggregation under static conditions.

PMID- 24883129
TI  - Middle-preserving pancreatectomy for multifocal intraductal papillary mucinous
      neoplasms of the pancreas: report of a case.
AB  - Multifocal or continuous pancreatic lesion is identified frequently but finding
      an appropriate surgical approach is quite challenging. Total pancreatectomy is a
      useful procedure. However, postoperative endocrine and exocrine disturbance is
      inevitable. Recently, the safety and feasibility of parenchyma preserving
      pancreatectomy, including middle-preserving pancreatectomy (MPP), have been
      reported. MPP is a combined procedure of pancreaticoduodenectomy and distal
      pancreatectomy, while preserving the body of the pancreas, for cases of
      multifocal pancreatic lesions. So far, there have only been a few reports that
      have described MPP. We report a case of MPP for multifocal intraductal papillary
      mucinous neoplasms of the pancreas, describe the surgical procedure, and discuss
      the feasibility of MPP as parenchyma-preserving pancreatectomy with reference to
      the literature. 

PMID- 24883130
TI  - Sonographic anatomy of the ankle.
AB  - Ankle sonography is one of the most commonly ordered examinations in the field of
      osteoarticular imaging, and it requires intimate knowledge of the anatomic
      structures that make up the joint. For practical purposes, the examination can be
      divided into four compartments, which are analyzed in this pictorial essay: the
      anterior compartment, which includes the tibialis anterior, extensor hallucis
      longus, and extensor digitorum longus tendons; the accessory peroneus tertius
      tendon; and the extensor retinaculum; the medial compartment (tibialis posterior,
      flexor digitorum longus, and flexor hallucis longus tendons; the flexor
      retinaculum; the medial collateral-or deltoid-ligament, and the neurovascular
      bundle); the lateral compartment (peroneus longus, peroneus brevis, and peroneus
      quartus tendons; superior and inferior peroneal retinacula, lateral collateral
      ligament); and the posterior compartment (Achilles tendon, plantaris tendon,
      Kagar's triangle, superficial, and deep retrocalcaneal bursae). Scanning
      techniques are briefly described to ensure optimal visualization of the various
      anatomic structures. 

PMID- 24883128
TI  - Diagnosis and management of intestinal Behcet's disease.
AB  - Behcet's disease (BD) is a chronic relapsing disease with multiple organ system
      involvement characterized clinically by oral and genital aphthae, cutaneous
      lesions, and ophthalmological, neurological, and/or gastrointestinal
      manifestations. Little clinical evidence is available regarding the management of
      patients with intestinal BD, despite recognition that the presence of intestinal
      lesions is a poor prognostic factor, causing perforation and massive bleeding.
      Many recent case reports have suggested that anti-tumor necrosis factor alpha
      (TNF)alpha monoclonal antibodies (mAbs) are effective in patients with intestinal
      BD. Adalimumab, a fully human anti-TNFalpha mAb, has been approved in Japan for
      the treatment of intestinal BD. Here, we review the pathogenesis, diagnosis and
      management of intestinal BD, including evidence of the efficacy of anti-TNFalpha
      mAbs. 

PMID- 24883131
TI  - US in ankle impingement syndrome.
AB  - Ankle impingement is a common condition occurring secondary to sprain or repeated
      microtrauma. Clinical symptoms are chronic pain located in the affected region
      and limited range of ankle motion. There are three types of ankle impingement
      syndrome: anterior impingement, which can be subdivided into anterolateral,
      anteromedial and purely anterior impingement; posterior impingement, which can be
      subdivided into posterior and posteromedial impingement; and calcaneal peroneal
      impingement which is secondary to planovalgus foot deformity. This paper
      evaluates physiological and clinical elements of these three types of ankle
      impingement syndrome as well as the role of ultrasound (US) imaging and US-guided
      treatment. 

PMID- 24883132
TI  - Ultrasound of tibialis anterior muscle and tendon: anatomy, technique of
      examination, normal and pathologic appearance.
AB  - Lesions of the tibialis anterior muscle and tendon are not frequently reported in
      international literature although pathology is not rare. Pathology can be
      spontaneous, associated with arthropathy or more generalized conditions. Clinical
      assessment may not be sufficient for distinguishing conditions like tendinopathy,
      tears, bursitis, etc. Therefore, imaging studies are necessary to plan
      appropriate therapy. US has a number of advantages, including widespread
      availability, absence of contraindications and low cost. It can also be used for
      dynamic studies of the muscle during contraction and relaxation. This article
      reviews the anatomy of the tibialis anterior, normal variants, the technique used
      for standard US examination of this muscle and tendon, its normal appearance on
      US and the sonographic characteristics of the most common lesions that affect it
      including tips on US-guided injections used for treatment. 

PMID- 24883134
TI  - Sonography of the ankle.

PMID- 24883133
TI  - US in mid-portion Achilles tendon injury.
AB  - Ultrasound (US) is the primary imaging technique used to evaluate pathologies
      affecting the tendons, as the use of high frequency probes permits a detailed
      study of the structure and morphology of the area also during dynamic
      examinations. The mid-portion of the Achilles tendon is well evaluated both in
      normal and pathological conditions, such as tendinosis and peritendinitis as well
      as partial-thickness and full-thickness tears. The role of US is essential to the
      diagnosis and, therefore, also to treatment planning in major disorders affecting
      the Achilles tendon. US furthermore allows the clinician to monitor the
      effectiveness of treatment over time as well as the risk of recurrent rupture
      after surgery. 

PMID- 24883135
TI  - Role of ultrasound in posteromedial tarsal tunnel syndrome: 81 cases.
AB  - Posteromedial tarsal tunnel syndrome is a disorder affecting the tibial nerve or
      its branches. Diagnosis is established on the basis of physical examination and
      can be confirmed by electrophysiological evidence. However, diagnostic imaging is
      always required to identify the possible site of compression. High-resolution
      ultrasound (US) is playing an increasingly important role in the study of the
      nerves thanks to a series of advantages over magnetic resonance imaging, such as
      lower costs and widespread availability, high spatial resolution, fast
      examination using axial scans, dynamic and comparative studies, possibility of
      carrying out a study with the patient in the standing position, US Tinel sign
      finding, and the contribution of color/power Doppler US. We present the results
      obtained in a series of 81 patients who underwent US imaging between 2008 and
      2013 due to posteromedial tarsal tunnel syndrome. 

PMID- 24883136
TI  - US in peroneal tendon tear.
AB  - Peroneal tendon injuries are common also due to the recent increase in sports
      participants involved in amateur activities. Clinical evaluation generally
      provides a diagnosis, but diagnostic imaging is often required to confirm a
      clinical suspicion and make correct management decisions. Ultrasound (US) imaging
      is the method of choice in the study of peroneal tendon injuries due to the high
      resolution of the images and the possibility of performing dynamic studies. US is
      furthermore non-invasive and inexpensive and provides the possibility of
      performing US-guided steroid infiltration of the tendon sheath or the surrounding
      tissues. The present paper will address the normal anatomy of the peroneal
      tendons and related structures, US imaging techniques and the various conditions
      and injuries which may affect this anatomic region. Also more expensive imaging
      techniques, such as computed tomography and magnetic resonance imaging, will be
      mentioned as well as their indications; however, they are required only in rare
      cases in which diagnosis remains uncertain or for pre-operative assessment. 

PMID- 24883137
TI  - Sonographic evaluation of hindfoot disorders.
AB  - Foot pain is a common orthopedic condition that can have an impact on health
      related quality of life. The evaluation of plantar hindfoot pain begins with
      history and physical examination. Imaging modalities, standard radiographs,
      sonography, MR, CT are often utilized to clarify the diagnosis. The article is a
      detailed description of the sonographic evaluation of the plantar fascia and its
      disorders as well as the common etiologies in the differential diagnosis of
      plantar fasciopathy. 

PMID- 24883138
TI  - Practical US of the forefoot.
AB  - Disorders affecting the forefoot are common in the clinical practice. Accurate
      history and physical examination are the mainstays of diagnosis but imaging
      modalities are frequently obtained to confirm the clinical suspicion and plan
      appropriate treatment. In this article we will present the ultrasound (US)
      technique of examination of the forefoot followed by a brief description of the
      normal US anatomy and of US appearance of the most frequent forefoot disorders;
      rheumatoid arthritis, osteoarthritis, overuse arthropathy, Morton neuromas,
      bursitis, mucoid cysts, foreign bodies, bone disorders. 

PMID- 24883139
TI  - Complete Achilles tendon rupture after local infiltration of corticosteroids in
      the treatment of deep retrocalcaneal bursitis.
AB  - Complete rupture of the Achilles tendon is relatively rare, but it is an injury
      of considerable clinical relevance. A common cause of non-traumatic tendon
      rupture is local corticosteroid infiltration. Corticosteroid injections may start
      a degenerative process resulting in partial rupture and subsequent complete
      rupture of the tendon due to a direct toxic effect, because corticosteroids
      inhibit production of extracellular matrix collagen and also because of poor
      local vascularization. This paper describes the case of a patient who presented
      with complete rupture of the Achilles tendon shortly after administration of
      local corticosteroid injections in the treatment of deep retrocalcaneal bursitis.
      This confirms that corticosteroid treatment which is not correctly and accurately
      administered may be a factor contributing to major injury. It demonstrates that
      the physician must take all necessary precautions when administering
      corticosteroid infiltration. It is particularly important that corticosteroid
      injection is performed under ultrasound guidance which permits visualization of
      the needle tip and therefore exact identification of the injection site. 

PMID- 24883140
TI  - Single hypovascular focal splenic lesion from Bartonella henselae infection.

PMID- 24883141
TI  - Herlyn Werner Wunderlich syndrome (HWWS): an unusual presentation of acute
      abdominal pain.

PMID- 24883142
TI  - Towards personal health care with model-guided medicine: long-term PPPM-related
      strategies and realisation opportunities within 'Horizon 2020'.
AB  - At the international EPMA Summit carried out in the EU Parliament (September
      2013), the main challenges in Predictive, Preventive and Personalised Medicine
      have been discussed and strategies outlined in order to implement scientific and
      technological innovation in medicine and healthcare utilising new strategic
      programmes such as 'Horizon 2020'. The joint EPMA (European Association for
      Predictive, Preventive and Personalised Medicine) / IFCARS (International
      Foundation for Computer Assisted Radiology and Surgery) paper emphasises the
      consolidate position of the leading experts who are aware of the great
      responsibility of being on a forefront of predictive, preventive and personalised
      medicine. Both societies consider long-term international partnerships and
      multidisciplinary projects to create PPPM relevant innovation in science,
      technological tools and practical implementation in healthcare. Personalisation
      in healthcare urgently needs innovation in design of PPPM-related medical
      services, new products, research, education, didactic materials, propagation of
      targeted prevention in the society and treatments tailored to the person. For the
      paradigm shift from delayed reactive to predictive, preventive and personalised
      medicine, a new culture should be created in communication between individual
      professional domains, between doctor and patient, as well as in communication
      with individual social (sub)groups and patient cohorts. This is a long-term
      mission in personalised healthcare with the whole spectrum of instruments
      available and to be created in the field. 

PMID- 24883143
TI  - Wegener's granulomatosis of the breast: A case report.
AB  - BACKGROUND: Differential diagnosis and detection of malignant lesions in
      mammography poses a challenge for many diagnosticians. Although mammography
      continues to be the best and cost-effective way to detect breast cancer, it has
      its limitations due in part to the radiological appearance of changes of a very
      rare condition. We are presented with changes that have met well-known radiologic
      criteria for the diagnosis of malignancy, yet they turn out to be benign, because
      they belong to a group of extraordinary lesions. CASE REPORT: In June 2010, a 56
      year-old woman found a lump in her right breast. Mammography performed at another
      medical center, revealed a change 12 mm in diameter, rated as BI-RADS 4C.
      Physical examination revealed a palpable lesion, 15 mm in diameter.
      Ultrasonography revealed hypoechogenic change with ill-defined outlines, size
      14*10 mm - BI-RADS 5. Fine needle aspiration biopsy was done and revealed no
      atypical cells. The patient underwent an open surgical biopsy and a
      histopathological diagnosis was suggested to be a type of Wegener's
      granulomatosis. Exclusion of cancer enabled the continuation of medical treatment
      of the underlying disease. There were no changes in the breast in follow-up
      studies. CONCLUSIONS: The differential diagnosis of breast tumors should include
      rare conditions that can sometimes mimic breast cancer. One of them is Wegener's
      granulomatosis. Both, the diagnosis and treatment of the disease, require the
      cooperation of specialists from various fields, including clinicians,
      pathologists and radiologists.

PMID- 24883144
TI  - Evaluation of the relationship between smear positivity and high-resolution CT
      findings in children with pulmonary tuberculosis.
AB  - BACKGROUND: The aim of this study is to find a relationship between the
      radiological manifestations of childhood tuberculosis on a high-resolution
      computed tomography (HRCT) and the results of sputum smear. This study aims to
      propose an alternative indicator of infectivity in terms of prevention of disease
      transmission through selective isolation policy in children whose clinical
      condition is highly suggestive of tuberculosis. MATERIAL/METHODS: This
      retrospective comparative study was performed on 95 children under 15 years of
      age diagnosed with tuberculosis based on both WHO criteria and positive sputum
      culture for mycobacterium Tuberculosis. The children were admitted for TB
      screening in the pediatric department of national research institute of
      tuberculosis and lung disease (NRITLD) between 2008-2012. Direct smear collected
      from sputum or gastric lavage, as well as HRCT were performed in all children
      prior to administration of medical therapy. Children were divided into 2 groups
      based on positive and negative smear results. HRCT abnormalities, as well as
      their anatomical distribution were compared between these 2 groups using
      multivariate analytic model. RESULTS: The most prevalent abnormalities in the
      positive smear group were consolidation, tree-in-bud pattern, upper lobe nodular
      infiltration and cavitation. The negative smear group featured lymphadenopathy,
      consolidation, collapse and nodular infiltration in the upper lobe. Cavity, tree-
      in-bud pattern and upper lobe nodular infiltration were highly associated with
      smear positivity in children. Conversely, lymphadenopathy and collapse had
      significant association with a negative smear. CONCLUSIONS: This study revealed
      that cavity, tree-in-bud and upper lobe nodular infiltration has significant
      association with smear positivity in childhood tuberculosis. On the other hand,
      lymphadenopathy and collapse were closely associated with smear negativity in
      this age group. It was also demonstrated that children with a positive smear most
      likely presented with radiological features of post primary tuberculosis, while
      the negative smear group most often manifested with primary tuberculosis.

PMID- 24883145
TI  - Pharmacokinetic changes and dosing modification of aminoglycosides in critically
      ill obese patients: a literature review.
AB  - The objective of the paper is to review the literature and provide
      recommendations for use of aminoglycoside antibiotics in critically ill obese
      patients. Literature search in PubMed for all articles on the use of
      aminoglycosides in critically ill obese patients was conducted, and all articles
      related to pharmacokinetics in obesity were reviewed. Bibliographies of all
      searched manuscripts were also reviewed in an attempt to find additional
      references. Although aminoglycoside pharmacokinetics have been described in
      detail, data on aminoglycoside use and appropriate dose modification in
      critically ill obese patients are very limited. Knowledge on aminoglycoside
      pharmacokinetics and use in critically ill obese patients is incomplete.
      Pathophysiologic changes in obesity can result in sub- or supra-therapeutic
      aminoglycoside plasma concentrations, especially in the presence of sepsis.
      Rigorous clinical studies are needed to establish aminoglycoside dosing
      guidelines in critically ill obese patients with sepsis. 

PMID- 24883146
TI  - Palliative dialysis: a change of perspective.
AB  - The aging phenomenon of dialysis patients is a worldwide reality, observed in
      developed and developing countries. Those patients have high incidence of chronic
      conditions along with high mortality rates and for some of them a decline in
      functional status within the first 12 months of dialysis therapy. Nevertheless,
      the elderly dialysis patients represent a very heterogeneous group where
      prognostic tools may help the decision-making process together with family
      members, medical staff and the patients. Despite the fact that there are many
      validated prognostic tools in elderly population, no score has the aim to guide
      the decision to withhold or withdrawn the dialysis procedure; therefore, in many
      cases, a time-limited trial is supported. After the failure of improvement in
      life quality and certitude of the poor prognosis, the withdrawing from renal
      replacement therapy can be done. Medical literature, from developed countries,
      brings robust evidence that the process of withdrawing the dialysis procedure,
      after a fail in the so-called "time-limited trial", along with good quality
      palliative care in this scenario is related to a good quality of death. We, on
      the other hand, believe that the withdrawing process in countries where hospice
      and good palliative care is not a reality may be associated with bad outcomes.
      Therefore, this review discusses a way to improve end-of-life symptoms in
      countries where palliative care facilities are not a reality, the so-called
      "palliative dialysis". 

PMID- 24883148
TI  - Evaluation of the timeliness of psychiatric consultations.
AB  - BACKGROUND: Emergency department (ED) delays have multiple causes and create
      frustration for patients and staff alike. METHODS: New adult psychiatric ED
      consultations were studied. Elapsed time between workflow stages was tested as a
      predictor of total time from triage to disposition. To expedite interviews a one
      page form was provided for interested patients to complete before psychiatric
      evaluation. RESULTS: Total ED time best correlated with time from rooming to
      consultation request. Total time was not predicted by time to rooming, or from
      consultation request to arrival of the psychiatric team. CONCLUSIONS: The
      intervention appeared to significantly reduce interview times. Variation among
      physicians regarding protocol for psychiatric consultation requests underscored
      the importance of standardization in quality improvement efforts.

PMID- 24883147
TI  - Appendicectomy and clostridium difficile infection: is there a link?
AB  - Clostridium difficile infection (CDI) is a gradually emerging healthcare problem
      in the western world, occurring predominantly from the de-arrangement of the gut
      microbiota and the widespread use of antibiotics. Recently, it has been proposed
      that the presence or absence of the appendix could be a factor influencing the
      occurrence and/or the severity of CDI. We performed a review of the literature,
      aiming to identify and interpret in an accumulative way the results of the
      published clinical studies which addressed the issue of a possible association
      between prior appendicectomy and the features of CDI. A total of five suitable
      studies were retrieved, which were all conducted retrospectively. Although the
      results were conflicting regarding the impact of prior appendicectomy in the
      occurrence and relapse of CDI, it appears that the presence or absence of the
      appendix is not associated with the clinical severity of CDI. Based on the
      current evidence and considering the effects of the widespread use of antibiotics
      in the clinical practice, it appears that an in situ appendix does not have a
      definitive impact on the development and severity of CDI. Further observational
      studies are warranted to clarify any potential association. 

PMID- 24883149
TI  - Angiotensin-converting enzyme gene polymophism in adult primary focal segmental
      glomerulosclerosis.
AB  - BACKGROUND: Primary focal segmental glomerulosclerosis (FSGS) accounts for a
      third of biopsy-proven primary glomerulonephritis in Malaysia. Pediatric studies
      have found the insertion/deletion (I/D) polymorphism of the angiotensin
      converting enzyme (ACE) gene to be associated with renal disease progression. The
      aim of this study was to determine the prevalence of the ACE (I/D) genotypes in
      adult primary FSGS and its association with renal outcome on follow-up. METHODS:
      Prospective observational study involving primary FSGS patients was conducted.
      Biochemical and urine tests at the time of study were compared to the time of the
      diagnosis and disease progression analyzed. ACE gene polymorphism was identified
      using polymerase chain reaction amplification technique and categorized into II,
      ID and DD genotypes. RESULTS: Forty-five patients with a median follow-up of 3.8
      years (interquartile range: 1.8 - 5.6) were recruited. The commonest genotype was
      II (n = 23, 51.1%) followed by ID (n = 19, 42.2%) and DD (n = 3, 6.7%). The
      baseline characteristics were comparable between the II and non-II groups at
      diagnosis and at study recruitment except that the median urine protein
      creatinine index was significantly lower in the II group compared to the non-II
      group (0.02 vs. 0.04 g/mmol (P = 0.03). Regardless of genotypes, all parameters
      of renal outcome improved after treatment. CONCLUSION: The II followed by ID
      genotypes were the predominant ACE gene alleles in our FSGS. Although the D
      allele has been reported to have a negative impact on renal outcome, treatment
      appeared to be more important than genotype in preserving renal function in this
      cohort.

PMID- 24883150
TI  - Risk Factors for Early-Onset Peripheral Neuropathy Caused by Vincristine in
      Patients With a First Administration of R-CHOP or R-CHOP-Like Chemotherapy.
AB  - BACKGROUND: Peripheral neuropathy is a well-known side effect of vincristine
      (VCR), a microtubule inhibitor used for R-CHOP or R-CHOP-like (namely R-CVP and R
      THP-COP) regimens. Previous studies have shown that both the total dose of VCR
      and the number of treatment cycles are related to the incidence of VCR-induced
      peripheral neuropathy (VIPN). However, VIPN will also occur during the first
      treatment cycle regardless of the total dose of VCR or number of treatment cycles
      (early-onset VIPN). There is little information about early-onset VIPN, and it is
      difficult to predict. The present study's goal was to identify risk factors for
      early-onset VIPN. METHODS: We analyzed the case records of patients who had their
      first administration of an R-CHOP or R-CHOP-like regimen between April 2008 and
      August 2013 at Tokushima University Hospital in Tokushima, Japan. To identify the
      risk factors for early-onset VIPN, we performed univariate and multivariate
      logistic regression analyses. RESULTS: Forty-one patients underwent an R-CHOP or
      R-CHOP-like regimen for the first time at Tokushima University Hospital between
      April 2008 and August 2013, and 14 patients had grade 1 or higher early-onset
      VIPN. A univariate analysis revealed that age, the dose of VCR and the
      concomitant use of aprepitant appeared to be the risk factors of early-onset
      VIPN. In our calculation using receiver-operator characteristics curves, the cut
      off value for patient age was 65 years and that of the dose of VCR was 1.9 mg. A
      multivariate analysis revealed that VCR dose >= 1.9 mg and the concomitant use of
      the antiemetic aprepitant were independent risk factors for early-onset VIPN.
      CONCLUSIONS: Our present study showed that the patients who had VCR dose >= 1.9
      mg and the concomitant use of aprepitant had the risk for early-onset VIPN. This
      suggests that it is important to use aprepitant in light of the risk of early
      onset VIPN and the benefit of aprepitant's antiemetic effect in R-CHOP and R-CHOP
      like regimens.

PMID- 24883152
TI  - The role of a radiology electronic notification system in the emergency
      department setting and its impact on patient care.
AB  - BACKGROUND: To determine the impact of a radiology electronic notification system
      (ENS) on emergency department (ED) patient care. MATERIALS AND METHODS: A
      retrospective review of de-identified patient data for a 2-year period (1 year
      prior to and 1 year following ENS implementation) was approved by the hospital's
      institutional review board. The effect of a radiology ENS on ED patient care was
      investigated by analyzing the intervals between completion of a chest radiograph
      and the times antibiotics were ordered/administered on patients presenting with
      symptoms of community acquired pneumonia (CAP). The square root transformation of
      the means was analyzed with an ANOVA model to determine statistical significance.
      RESULTS: During the 24-month study protocol, 1,341 patients who were evaluated in
      the ED met the study eligibility criteria. The least square estimates of the mean
      times from when the chest radiograph was completed to when antibiotics were
      ordered prior to and after the implementation of the ENS were 89 and 107 minutes,
      respectively (P < 0.01). The least square estimates of the mean times from when
      the chest radiograph was completed to when antibiotics were administered prior to
      and after the implementation of the ENS were 115 and 132 minutes, respectively (P
      = 0.02). CONCLUSION: The implementation of a radiology ENS does have advantages
      for the radiologist in streamlining the communication and documentation processes
      but may negatively impact time to treatment and thus patient care.

PMID- 24883151
TI  - Lessons learned with laparoscopic management of complicated grades of acute
      appendicitis.
AB  - BACKGROUND: Laparoscopy has not been consolidated as the approach of first choice
      in the management of complicated appendicitis. Methodological flaws and absence
      of disease stratification criteria have been implicated in that less evidence.
      The objective is to study the safe and effectiveness of laparoscopy in the
      management of complicated appendicitis according to laparoscopic grading system.
      METHOD: From January 2008 to January 2011, 154 consecutive patients who underwent
      a laparoscopic appendectomy for complicated appendicitis were evaluated in the
      prospective way. The patient's age ranged from 12 to 75 years old (31.7 +/- 13.3)
      and 58.3% were male. Complicated appendicitis refers to gangrenous and/or
      perforated appendix and were graded as 3A (segmental necrosis), 3B (base
      necrosis), 4A (abscess), 4B (regional peritonitis) and 5 (diffuse peritonitis).
      The outcomes including operative time, infection complication, operative
      complications and conversion rate were chosen to evaluate the procedure. RESULTS:
      The grade 3A was the most frequent with 50 (32.4%) patients. The mean operative
      time was 69.4 +/- 26.3 minutes. The grade 4A showed the highest mean operative
      time (80.1 +/- 26.7 minutes). The wound and intra-abdominal infection rates were
      2.6 and 4.6%, respectively. The base necrosis was the most important factor
      associated with the conversion (5.2%). The grades 4A and 5 were associated with
      greater possibility of intra-abdominal collection. There were no operative
      complications. CONCLUSION: The laparoscopic management of all complicated grades
      of acute appendicitis is safe and effective and should be the procedure of first
      choice. The laparoscopic grading system allows us to assess patients in the same
      disease stage.

PMID- 24883153
TI  - Vertebral osteomyelitis: an under-recognized infectious complication in patients
      on home parenteral nutrition.
AB  - BACKGROUND: Patients on home parenteral nutrition (HPN) are at high risk of
      central venous catheter sepsis (CVCS). CVCS can be associated with distant
      bacterial seeding. However, few cases of vertebral osteomyelitis (VO) related to
      HPN have been reported. For this reason, we made the hypothesis that the
      incidence of VO in patients on HPN is probably higher than what is reported. The
      goal of this study was to evaluate the incidence of infectious complications, and
      more specifically, the incidence of VO in patients on HPN. METHODS: A
      retrospective study of all patients receiving HPN from 2001 to 2006 was
      conducted. Patients who received HPN for < 1 month were excluded. Infectious
      complications and, more specifically, cases of VO were searched. RESULTS: Thirty
      one patients received HPN and were included in the analysis. Forty-four
      infectious complications occurred (1.302/1,000 CVC-days). The most frequent
      infectious complication was urinary tract infection (25 cases; 0.740/1,000 CVC
      days). Seven CVCS occurred in five different patients (0.207/1,000 CVC-days). In
      patients with CVCS, 42.9% (three cases) developed a secondary VO. No predictive
      factors for the development of VO could be identified in univariate analysis.
      CONCLUSION: We report a very low rate of infectious complications and an even
      lower rate of CVCS in patients on HPN. However, we report that 42.9% of our cases
      of CVCS developed a secondary VO. Consequently, VO must be part of the
      differential diagnosis among patients with HPN who complain of back pain.

PMID- 24883154
TI  - Prevalence of elevated glycated hemoglobin concentrations in the polycystic ovary
      syndrome: anthropometrical and metabolic relationship in amazonian women.
AB  - BACKGROUND: To determine the prevalence of elevated glycated hemoglobin (HbA1c)
      and to examine its relationship with other carbohydrate metabolic parameter among
      Brazilian women with polycystic ovary syndrome (PCOS). METHODS: A cross-sectional
      study including 288 PCOS patients was conducted. Anthropometrical, clinical,
      biochemical and endocrine parameters were evaluated. RESULTS: The mean age was
      26.92 +/- 5.51 years. HbA1c mean concentration was 5.83+/-1.34%. In 38.54% of
      patients, HbA1c was >= 5.7%. HbA1c was positively correlated with body weight (r
      = 0.142, P = 0.017), body mass index (P = 0.000), waist:hip ratio (P = 0.000),
      fat mass (P = 0.000), conicity index (P = 0.000), triglyceride (P = 0.001), C
      peptide (P = 0.000), total testosterone (P = 0.003), free testosterone (P =
      0.000), free androgen index (P = 0.006) and fasting insulin (P = 0.025). Using
      the oral glucose tolerance test, HbA1c showed positive correlation with glucose
      concentrations at any point in time (P < 0.05). CONCLUSIONS: HbA1c was elevated
      in nearly 40% of PCOS patients and it showed positive correlation with several
      anthropometric and metabolic factors and androgen levels. The current study
      provides further evidence that HbA1C is higher in PCOS patients and may have a
      potential role in the prediction of dysglycemic disease in these women.

PMID- 24883155
TI  - Teneligliptin as an initial therapy for newly diagnosed, drug naive subjects with
      type 2 diabetes.
AB  - BACKGROUND: Teneligliptin is a novel, highly selective dipeptidyl peptidase-4
      (DPP-4) inhibitor. The aim of this study is to explore the glycemic and non
      glycemic efficacies of teneligliptin as an initial therapy. METHODS: Newly
      diagnosed, drug naive Japanese subjects with type 2 diabetes (T2DM) were assigned
      to 20 mg/day teneligliptin monotherapy (n = 31). At 3 months, levels of glycemic
      and other parameters were compared with those at baseline. RESULTS: Significant
      reductions of HbA1c (from 10.34 +/- 2.06 to 8.38 +/- 2.23%) and fasting blood
      glucose (FGB, from 211.3 +/- 68.4 to 167.3 +/- 70.2 mg/dL) levels were observed
      without any clinically significant adverse events. However, significant increases
      of uric acids (UA) levels were observed and two subjects reported mild
      hypoglycemic events. Homeostasis model assessment-B (HOMA-B) levels significantly
      increased, while high HOMA-R levels significantly decreased. Significant
      correlations were observed between the changes (Delta) of HbA1c and those of HOMA
      B, and between DeltaFBG and DeltaHOMA-R. No changes in lipid and body weight were
      noted. CONCLUSIONS: Teneligliptin might be effectively and safely used as an
      initial therapy for newly diagnosed T2DM. Glycemic efficacy of teneligliptin is
      obtained through activating beta-cell function as well as decreasing insulin
      resistance.

PMID- 24883156
TI  - IgG4-Related Esophageal Disease Presenting as Esophagitis Dissecans Superficialis
      With Chronic Strictures.
AB  - IgG4-related disease is a recently recognized autoimmune systemic disorder that
      has been described in various organs. The disease is characterized histologically
      by a dense lymphoplasmocytic infiltrate of IgG4-positive cells, storiform
      fibrosis and can be associated with tumefactive lesions. IgG4-related disease
      involving the upper gastrointestinal tract is rare and only two previous case
      reports have reported IgG4-related esophageal disease. We report the case of a 63
      year-old female patient with a long-standing history of severe dysphagia and
      odynophagia with an initial diagnosis of reflux esophagitis. Symptoms persisted
      despite anti-acid therapy and control esophagogastroduodenoscopy (EGD) revealed
      endoscopic images consistent with esophagitis dissecans superficialis (sloughing
      esophagitis). An underlying autoimmune process was suspected and
      immunosuppressant agents were tried to control her disease. The patient
      eventually developed disabling dysphagia secondary to multiple chronic esophageal
      strictures. A diagnosis of IgG4-related disease was eventually made after
      reviewing esophageal biopsies and performing an immunohistochemical study with an
      anti-IgG4 antibody. Treatment attempts with corticosteroids and rituximab was not
      associated with a significant improvement of the symptoms of dysphagia and
      odynophagia, possibly because of the chronic nature of the disease associated
      with a high fibrotic component. Our case report describes this unique case of
      IgG4-related esophageal disease presenting as chronic esophagitis dissecans with
      strictures. We also briefly review the main histopathological features and
      treatment options in IgG4-related disease. 

PMID- 24883157
TI  - Near misdiagnosis of glioblastoma as primary central nervous system lymphoma.
AB  - Primary central nervous system (CNS) lymphoma, most frequently a diffuse large B
      cell lymphoma, is a rare aggressive lymphoma confined to the CNS, thus requiring
      differentiation from other brain malignancies such as glioblastoma. Although
      stereotactic biopsy can confirm the diagnosis, this is invasive, not always
      feasible and can be inconclusive after steroid use. Hence, cranial magnetic
      resonance imaging (MRI) with contrast and cerebrospinal fluid analysis are
      frequently used to make a prompt diagnosis. We report a case of a woman with two
      brain masses who presented unique diagnostic challenge. 

PMID- 24883158
TI  - Acute acalculous cholecystitis in patients with clear cell renal cell carcinoma
      treated with sunitinib: report of two cases.
AB  - Although sunitinib is associated with a variety of adverse events, cases of
      sunitinib-related acute cholecystitis have rarely been reported. We herein report
      two cases of sunitinib-related acute acalculous cholecystitis in patients with
      clear cell renal cell carcinoma. In both cases, the gallbladder was surgically
      removed because it was difficult to improve the patient's condition with the
      cessation of sunitinib and non-surgical treatment only. Attention must be paid to
      the possibility of sunitinib-related acute cholecystitis, which, although
      uncommon, can be life-threatening. 

PMID- 24883159
TI  - Autoimmune Disease pH and Temperature.

PMID- 24883160
TI  - Special issue on fitness to drive.

PMID- 24883161
TI  - Geriatric rehabilitation patients' perceptions of unit dining locations.
AB  - BACKGROUND: Eating together is promoted among hospitalized seniors to improve
      their nutrition. This study aimed to understand geriatric patients' perceptions
      regarding meals in a common dining area versus at the bedside. METHODS: An
      exploratory qualitative study was conducted. Open-ended questions were asked of
      eight patients recruited from a geriatric rehabilitation unit where patients had
      a choice of meal location. RESULTS: Eating location was influenced by compliance
      with the perceived rules of the unit, physical and emotional well-being, and
      quarantine orders. Certain participants preferred eating in the common dining
      room where they had more assistance from hospital staff, a more attractive
      physical environment, and the opportunity to socialize. However, other
      participants preferred eating at their bedsides, feeling the quality of social
      interaction was poor in the dining room. CONCLUSIONS: Participants' experiences
      of, and preferences for, communal dining differed. If the benefits of communal
      dining are to be maximized, different experiences of this practice must be
      considered.

PMID- 24883163
TI  - Geriatric core competencies for family medicine curriculum and enhanced skills:
      care of elderly.
AB  - BACKGROUND: There is a growing mandate for Family Medicine residency programs to
      directly assess residents' clinical competence in Care of the Elderly (COE). The
      objectives of this paper are to describe the development and implementation of
      incremental core competencies for Postgraduate Year (PGY)-I Integrated Geriatrics
      Family Medicine, PGY-II Geriatrics Rotation Family Medicine, and PGY-III Enhanced
      Skills COE for COE Diploma residents at a Canadian University. METHODS: Iterative
      expert panel process for the development of the core competencies, with a pre
      defined process for implementation of the core competencies. RESULTS: Eighty-five
      core competencies were selected overall by the Working Group, with 57 core
      competencies selected for the PGY-I/II Family Medicine residents and an
      additional 28 selected for the PGY-III COE residents. The core competencies
      follow the CanMEDS Family Medicine roles. Both sets of core competencies are
      based on consensus. CONCLUSIONS: Due to demographic changes, it is essential that
      Family Physicians have the required skills and knowledge to care for the frail
      elderly. The core competencies described were developed for PGY-I/II Family
      Medicine residents and PGY-III Enhanced Skills COE, with a focus on the
      development of geriatric expertise for those patients that would most benefit.

PMID- 24883162
TI  - Increased health service utilization costs in the year prior to
      institutionalization: findings from the canadian study of health and aging.
AB  - OBJECTIVES: The objective of this study was to characterize patterns of formal
      health service utilization costs during older adults' transition from community
      to institutional care. METHODS: Participants were 127 adults (age >= 65) from the
      British Columbia sample (N = 2,057) of the Canadian Study of Health and Aging who
      transitioned from community to institutional care between 1991 and 2001. Health
      service utilization costs were measured using Cost-Per-Day-At-Risk at five time
      points: > 12 months, 6-12 months, and <= 6 months preinstitutionalization, and <=
      6 months and 6-12 months postinstitutionalization. Cost-Per-Day-At-Risk was
      measured for Continuing Care, Medical Services Plan, and PharmaCare costs by
      calculating total health service use over time, divided by the number of days the
      participant was alive. RESULTS: Significant differences in Cost-Per-Day-At-Risk
      were observed for Continuing Care, Medical Services Plan, and PharmaCare costs
      over time. All health service utilization costs increased significantly during
      the 6-12 months and <= 6 months prior to institutionalization.
      Postinstitutionalization Continuing Care costs continued to increase at <= 6
      months before decreasing at 6-12 months, while decreases occurred for Medical
      Services Plan and PharmaCare costs relative to preinstitutionalization costs.
      CONCLUSIONS: The increases in costs observed during the year prior to
      institutionalization, characterized by a flurry of health service utilization,
      provide evidence of distinct cost patterns over the transition period.

PMID- 24883164
TI  - Comparison of the SIMARD MD to Clinical Impression in Assessing Fitness to Drive
      in Patients with Cognitive Impairment.
AB  - BACKGROUND: The assessment of fitness to drive in patients with cognitive
      impairment is complex. The SIMARD MD was developed to assist with assessing
      fitness to drive. This study compares the clinical decision made by a
      geriatrician regarding driving with the SIMARD MD score. METHODS: Patients with a
      diagnosis of mild dementia or mild cognitive impairment, who had a SIMARD MD
      test, were included in the sample. A retrospective chart review was completed to
      gather diagnosis, driving status, and cognitive and functional information.
      RESULTS: Sixty-three patients were identified and 57 met the inclusion criteria.
      The mean age was 77.1 years (SD 8.9). The most common diagnosis was Alzheimer's
      disease in 22 (38.6%) patients. The mean MMSE score was 24.9 (SD 3.34) and the
      mean MoCA was 19.9 (SD 3.58). The mean SIMARD MD score was 37.2 (SD 19.54).
      Twenty-four patients had a SIMARD MD score <= 30, twenty-eight between 31-70, and
      five scored > 70. The SIMARD MD scores did not differ significantly compared to
      the clinical decision (ANOVA p value = 0.14). CONCLUSIONS: There was no
      association between the SIMARD MD scores and the geriatricians' clinical decision
      regarding fitness to drive in persons with mild dementia or mild cognitive
      impairment.

PMID- 24883165
TI  - Not if, but when: impact of a driving and dementia awareness and education
      campaign for primary care physicians.
AB  - BACKGROUND: Canadian physicians are responsible for assessing medical fitness to
      drive; however, national data indicate that physicians lack confidence in
      performing such assessments and face numerous barriers to addressing driving in
      patients with dementia. We report on the impact of a provincial Web-based
      resource (www.notifbutwhen.ca) regarding driving cessation in dementia aimed
      towards primary care physicians (PCPs). METHODS: A pre/post cross-sectional
      survey (n = 134 baseline and n = 113 follow-up) of English-speaking, Nova Scotian
      PCPs. Descriptive statistics, chi-square, Pearson correlation, and multivariable
      logistic regression (controlling for sex, years of practice, and practice type)
      are reported. RESULTS: Most PCPs consider discussions regarding driving cessation
      to be routine part of dementia care; however, report multiple barriers to such
      discussions. Although the Web-based resource and awareness campaign were not
      associated with improvement in physician comfort in assessing driving risk in
      dementia, after completion of the campaign, fewer PCPs reported avoiding the
      topic of driving. Additionally, family resistance and lack of resources were less
      often reported as barriers. CONCLUSIONS: Despite a lack of confidence, Nova
      Scotian PCPs routinely discuss driving cessation, and perform driving assessments
      for individuals with dementia. The Web-based resource and awareness campaign have
      shown moderate effectiveness in addressing specific barriers to assessment (e.g.,
      caregiver resistance, lack of resources). Future efforts will address additional
      barriers, such as lack of comfort in decision-making.

PMID- 24883166
TI  - Consensus statements on the assessment of older drivers.
AB  - BACKGROUND: The rapidly increasing number of older drivers is accentuating the
      challenges in concurrently identifying older drivers posing an unacceptable risk
      if they continue to drive, while not discriminating against those capable of
      safely driving. Attendees of an invitational meeting about the assessment of
      older drivers were asked to participate in a modified Delphi process designed to
      develop consensus statements on the assessment of older drivers. METHODS: Forty
      one non-student symposium attendees were invited to participate in two rounds of
      a survey, in which they were asked to indicate their level of agreement (or
      disagreement) on a five-point Likert scale to a series of statements about the
      assessment of older drivers. Consensus was defined as 80% + of respondents either
      agreeing or disagreeing with a statement. RESULTS: More than one-half (n = 23)
      completed the first round of the survey and 12 participated in the second. There
      was consensus on the need for a modifiable, fair, rational, and widely accessible
      multi-step approach to the assessment of older drivers. This would require the
      engagement and support of physicians and other health-care practitioners in
      identifying and reporting medically at-risk drivers of any age. At a societal
      level, alternatives to driving a personal motor vehicle should be developed.
      CONCLUSIONS: An on-going dialogue about this complex issue is required. Decisions
      should be based on explicitly stated principles and informed by the best
      available evidence.

PMID- 24883167
TI  - Evidence to Support the Pike's Peak Model: The UA Geropsychology Education
      Program.
AB  - The University of Alabama's Graduate Geropsychology Education program (GGE) was
      conceived and implemented in the years prior to the design of the Pike's Peak
      Model (PPM) of geropsychology training. The GGE program provides a unique
      opportunity to evaluate the PPM, and this paper outlines the GGE program in the
      framework of the model. Three primary goals defined the GGE program: recruitment
      and retention of students in the geropsychology program, a doctoral level
      interdisciplinary class, and a set of clinical rotations in urban and rural
      sites. Outcomes were promising, indicating that geropsychology students were able
      to provide services with positive outcomes to underserved older adults in primary
      care settings and in a legal clinic, students from several disciplines rated the
      course very highly, and psychology students indicated that they were likely to
      continue in the field of geriatric care. Participating students have gone on to
      careers in geropsychology. Findings from this program support the design of the
      Pike's Peak Model, and provide support for broader implementation of similar
      training programs.

PMID- 24883168
TI  - Quinacridone on Ag(111): Hydrogen Bonding versus Chirality.
AB  - Quinacridone (QA) has recently gained attention as an organic semiconductor with
      unexpectedly high performance in organic devices. The strong intermolecular
      connection via hydrogen bonds is expected to promote good structural order. When
      deposited on a substrate, another relevant factor comes into play, namely the 2D
      chirality of the quinacridone molecules adsorbed on a surface. Scanning tunneling
      microscopy (STM) images of monolayer quinacridone on Ag(111) deposited at room
      temperature reveal the formation of quasi-one-dimensional rows of parallel
      quinacridone molecules. These rows are segmented into short stacks of a few
      molecules in which adjacent, flat-lying molecules of a single handedness are
      linked via hydrogen bonds. After annealing to a temperature of T = 550-570 K,
      which is close to the sublimation temperature of bulk quinacridone, the structure
      changes into a stacking of heterochiral quinacridone dimers with a markedly
      different intermolecular arrangement. Electron diffraction (LEED) and
      photoelectron emission microscopy (PEEM) data corroborate the STM findings. These
      results illustrate how the effects of hydrogen bonding and chirality can compete
      and give rise to very different (meta)stable structures of quinacridone on
      surfaces.

PMID- 24883169
TI  - Proton Ordering of Cubic Ice Ic: Spectroscopy and Computer Simulations.
AB  - Several proton-disordered crystalline ice structures are known to proton order at
      sufficiently low temperatures, provided that the right preparation procedure is
      used. For cubic ice, ice Ic, however, no proton ordering has been observed so
      far. Here, we subject ice Ic to an experimental protocol similar to that used to
      proton order hexagonal ice. In situ FT-IR spectroscopy carried out during this
      procedure reveals that the librational band of the spectrum narrows and acquires
      a structure that is observed neither in proton-disordered ice Ic nor in ice XI,
      the proton-ordered variant of hexagonal ice. On the basis of vibrational spectra
      computed for ice Ic and four of its proton-ordered variants using classical
      molecular dynamics and ab initio simulations, we conclude that the features of
      our experimental spectra are due to partial proton ordering, providing the first
      evidence of proton ordering in cubic ice. We further find that the proton-ordered
      structure with the lowest energy is ferroelectric, while the structure with the
      second lowest energy is weakly ferroelectric. Both structures fit the
      experimental spectral similarly well such that no unique assignment of proton
      order is possible based on our results.

PMID- 24883170
TI  - Cross-Cultural Administration of an Odor Discrimination Test.
AB  - Olfactory sensitivity can be evaluated by various tests, with "Sniffin' Sticks"
      test (SST) being one of the most popular. SST consists of tests for odor
      threshold, discrimination, and identification. It seems relatively
      straightforward to administer threshold tests in different groups and societies
      and it has been shown that odor identification tests requires special adaptation
      before they can be administered to various populations. However, few studies have
      investigated the application of an odor discrimination task in various
      regions/cultures. In the present study, we compared the discrimination scores of
      169 Polish people with the scores of 99 Tsimane', Bolivian Amerindians. The
      Tsimane' participants scored very low in the discrimination task, despite their
      general high olfactory sensitivity. This result suggests that when a
      discrimination task is chosen as the form of olfactory testing, some additional
      variables need to be controlled. We suggest three sources of low scores of our
      participants-their cognitive profile, the cultural background, i.e., little
      knowledge of the odors used in the discrimination test and problems associated
      with testing environment.

PMID- 24883172
TI  - An exotic cause of exudative enteropathy.
AB  - PATIENT: Male, 50 FINAL DIAGNOSIS: Exudative enteropathy Symptoms: Abdominal pain
      * diarrhea * fever * hyponatremia * lymphadenopathy * weight loss MEDICATION: -
      Clinical Procedure: - Specialty: - OBJECTIVE: Unusual clinical course.
      BACKGROUND: Protein-losing enteropathy is a rare cause of hypoproteinemia.
      Erosive and non-erosive gastrointestinal diseases as well as vascular disorders
      that result in increased central venous pressure or mesenteric lymphatic
      obstruction may result in protein loss via the gastrointestinal tract. CASE
      REPORT: We present the case of a 50-year-old man with protein-losing enteropathy,
      who had profuse diarrhea, abdominal pain, lymphadenopathy, fever, and a weight
      loss of 10 kg in the preceding 2 months. Extensive work-up revealed infection
      with Giardia lamblia. We review clinical signs and symptoms, laboratory findings,
      and imaging studies, and discuss potential pitfalls in establishing the
      diagnosis. CONCLUSIONS: To the best of our knowledge, this represents one of the
      few published cases of intestinal giardiasis as a cause of protein-losing
      enteropathy in an immunocompetent adult. The diagnosis of lambliasis should be
      based on a combination of stool cultures and serum serology, and in cases of high
      clinical suspicion, an endoscopy and biopsy of the upper GI tract is recommended.

PMID- 24883171
TI  - Quantitative Validation of the n-Butanol Sniffin' Sticks Threshold Pens.
AB  - Odorant pens are used by medical practitioners and researchers to assess
      olfactory dysfunction. Despite their routine use, there are currently no data on
      the gas-phase odorant concentrations released from the pen tips or whether these
      concentrations scale linearly with the aqueous-phase concentrations inside the
      pens. The commercially available Sniffin' Sticks odor threshold test containing n
      butanol was chosen for evaluation. The gas-phase concentration of n-butanol at
      the tip of each pen was measured directly in a new set of pens via proton
      transfer-reaction mass spectrometry (PTR-MS). Measurements were additionally made
      on the same pens after 6 months and two older pen sets, namely a 3-year-old
      (used) and 4-year-old (new) set. Furthermore, application-related tests were made
      to determine the performance of the pens during routine use and under stress.
      These data demonstrate that the gas-phase n-butanol concentrations of the
      threshold pens are linear over the entire set, both for brand-new pens and 6
      months later; this reflects the expected performance that was previously only
      assumed. Furthermore, the application-simulation tests demonstrated a good
      performance of the pens when used according to their intended protocol.
      Measurements of the older pen sets suggest that storage conditions are more
      critical than usage for pen stability. The present findings confirm that the n
      butanol odorant pens are an appropriate tool for threshold testing, provided they
      are stored and handled correctly. Figure?

PMID- 24883173
TI  - The forgotten disease: Bilateral lemierre's disease with mycotic aneurysm of the
      vertebral artery.
AB  - PATIENT: Male, 25 FINAL DIAGNOSIS: Lemierre's disease Symptoms: Back pain * fever
      * headache * tachycardia * tachypnoe MEDICATION: - Clinical Procedure: -
      Specialty: Infectious Diseases. OBJECTIVE: Rare disease. BACKGROUND: Lemierre's
      disease, also known as the forgotten disease, postanginal sepsis, or
      necrobacillosis, was first reported in 1890 by Courmont and Cade, but it was Dr.
      Andre Lemierre, a professor of microbiology, who described this disease in 1936.
      The typical causative agent is Fusobacterium necrophorum, although other
      organisms may be involved. The pathogenesis of Lemierre's disease is not well
      understood. It is characterized by a primary oropharyngeal infection associated
      with septicemia, internal jugular vein thrombosis, and metastatic septic emboli.
      CASE REPORT: We report a case of Lemierre's disease with bilateral internal
      jugular vein (IJV) thrombosis and metastatic septic emboli to the lungs and
      brain, associated with epidural abscess and mycotic aneurysm of the vertebral
      artery, which is quite rare in Lemierre's disease. This is the first report of a
      case of Lemierre's disease associated with mycotic aneurysm of the vertebral
      artery. CONCLUSIONS: Lemierre's disease is a rare and perplexing medical entity.
      Clinical suspicion should be high in previously healthy young adults presenting
      with fever and neck pain following oropharyngeal infection. Dr. Lemierre stated
      that 'symptoms and signs of Lemierre's disease are so characteristic that it
      permits diagnosis before bacteriological examination'. The prognosis of patients
      with Lemierre's disease is generally good, provided prompt recognition and
      appropriate treatment.

PMID- 24883174
TI  - A Qualitative Descriptive Study of Perceived Sexual Effects of Club Drug Use in
      Gay and Bisexual Men.
AB  - Club drug use is often associated with unsafe sexual practices and use remains
      prevalent among gay and bisexual men. Although epidemiological studies commonly
      report the risk of engaging in unsafe sex due to the effects of particular club
      drugs, there remain gaps in the literature regarding the specific sexual effects
      of such substances and the context for their use in this population. We examined
      secondary data derived from interviews with 198 club drug using gay and bisexual
      males in New York City and qualitatively describe subjective sexual effects of
      five drugs: ecstasy, GHB, ketamine, powder cocaine and methamphetamine.
      Differences and commonalities across the five drugs were examined. Results
      suggest that each drug tends to provide: 1) unique sexual effects, 2) its own
      form of disinhibition, and 3) atypical sexual choices, often described as "lower
      sexual standards." Differences across drugs emerged with regard to social,
      sensual and sexual enhancement, sexual interest, and impotence. Although some
      common perceived sexual effects exist across drugs, the wide variation in these
      effects suggests different levels of risk and may further suggest varying
      motivations for using each substance. This study seeks to educate public health
      officials regarding the sexual effects of club drug use in this population.

PMID- 24883176
TI  - Methods for Assessing and Addressing Participant Protection Concerns in Intimate
      Partner Violence Research.
AB  - Research on intimate partner violence (IPV) is highly sensitive and may put some
      participants at increased psychological, emotional, and physical risk. Still, we
      know little about the risks posed by most social science methods and have minimal
      guidance regarding appropriate practices for carrying out various forms of
      research. This study collected data from 59 IPV researchers regarding the most
      commonly used participant protection methods, the efficacy of those methods,
      number and nature of adverse events (AE) experienced, and experiences with
      institutional review boards (IRBs). Participants were invited via e-mail to
      complete an anonymous online survey. Findings indicate an overall low incidence
      of AEs as well as a minimal relationship between AEs and IPV inquiry. These
      findings may provide researchers with preliminary data on the effectiveness of
      various participant protection methods. Results may also facilitate more
      innovative and effective participant protections measures, help researchers
      prevent and cope with AE, and create more mutually beneficial relationships with
      IRBs.

PMID- 24883177
TI  - Synthesis and evaluation of novel cyclic Peptide inhibitors of lysine-specific
      demethylase 1.
AB  - Lysine specific demethylase 1 (LSD1) selectively removes methyl groups from mono-
      and dimethylated histone 3 lysine 4 (H3K4), resulting in gene silencing. LSD1 is
      overexpressed in many human cancers, resulting in aberrant silencing of tumor
      suppressor genes. Thus, LSD1 is a validated target for the discovery of antitumor
      agents. Using a ligand-based approach, we designed and synthesized a series of
      cyclic and linear peptides that are effective inhibitors of LSD1. Linear peptide
      7 and cyclic peptide 9 inhibited LSD1 in vitro by 91 and 94%, respectively, at a
      concentration of 10 MUM. Compound 9 was a potent LSD1 inhibitor (IC50 2.1 MUM; K
      i 385 nM) and had moderate antitumor activity in the MCF-7 and Calu-6 cell lines
      in vitro. Importantly, 9 is significantly more stable to hydrolysis in rat plasma
      than the linear analogue 7. The cyclic peptides described herein represent
      important lead structures in the search for inhibitors of flavin-dependent
      histone demethylases. 

PMID- 24883178
TI  - Effect of green tea supplementation on the microbiological, antioxidant, and
      sensory properties of probiotic milks.
AB  - Green tea and its constituents are known for a wide range of health-promoting
      properties. They may exert antimicrobial action but without altering lactic acid
      bacteria. The aim of the present study was to estimate the effect of green tea
      addition on the selected properties of probiotic milks. Bioyogurts (fermented
      with ABT-1 coculture of Streptococcus thermophilus, Lactobacillus acidophilus LA
      5, Bifidobacterium animalis subsp. lactis BB-12) and acidophilus milks (fermented
      with pure L. acidophilus LA-5 culture) with addition of 0, 5, 10, or 15% (v/v)
      green tea infusion (GTI) were produced and analyzed for the antioxidant capacity
      by the "diphenyl picrylhydrazyl" (DPPH) and "ferric-reducing antioxidant power"
      (FRAP) methods, acidity, the count of starter bacteria, and sensory properties at
      the 1st, 7th, 14th, and 21st day of cold storage. The 15% addition of GTI to the
      acidophilus milk significantly reduced the lactic acid production during the
      whole study. The GTI had no impact on the level of S. thermophilus and B. lactis
      BB-12 in bioyogurts, and its effect on the count of L. acidophilus LA-5 depended
      on the concentration and probiotic milk type. GTI similarly and in a dose
      dependent manner enhanced the antioxidant capacity of both milk types. There were
      no significant differences between the sensory notes received for bioyogurts,
      whereas acidophilus milks with tea were less appreciated by the panelists. In
      conclusion, green tea could be successfully used as a functional additive for
      selected probiotic milks enhancing their health benefits, but the proper
      selection of tea additive and starter culture is recommended.

PMID- 24883175
TI  - Protein redox modification as a cellular defense mechanism against tissue
      ischemic injury.
AB  - Protein oxidative or redox modifications induced by reactive oxygen species (ROS)
      or reactive nitrogen species (RNS) not only can impair protein function, but also
      can regulate and expand protein function under a variety of stressful conditions.
      Protein oxidative modifications can generally be classified into two categories:
      irreversible oxidation and reversible oxidation. While irreversible oxidation
      usually leads to protein aggregation and degradation, reversible oxidation that
      usually occurs on protein cysteine residues can often serve as an "on and off"
      switch that regulates protein function and redox signaling pathways upon stress
      challenges. In the context of ischemic tolerance, including preconditioning and
      postconditioning, increasing evidence has indicated that reversible cysteine
      redox modifications such as S-sulfonation, S-nitrosylation, S-glutathionylation,
      and disulfide bond formation can serve as a cellular defense mechanism against
      tissue ischemic injury. In this review, I highlight evidence of cysteine redox
      modifications as protective measures in ischemic injury, demonstrating that
      protein redox modifications can serve as a therapeutic target for attenuating
      tissue ischemic injury. Prospectively, more oxidatively modified proteins will
      need to be identified that can play protective roles in tissue ischemic injury,
      in particular, when the oxidative modifications of such identified proteins can
      be enhanced by pharmacological agents or drugs that are available or to be
      developed. 

PMID- 24883180
TI  - Role of consolidation with yttrium-90 ibritumomab tiuxetan in patients with
      advanced-stage follicular lymphoma.
AB  - Non-Hodgkin's lymphoma (NHL) accounts for 4% of all cancers diagnosed in the
      United States. Follicular lymphoma (FL) is the most common type of indolent NHL
      with a survival from 5 to 15 years. Although it is very sensitive to chemotherapy
      and radiotherapy, relapses are the main cause of therapeutic failure, and
      currently there is no consensus on the first-line treatment and optimal
      therapeutic strategies for patients with FL. Immediate treatment offers any
      survival benefit for asymptomatic and more indolent disease. In order to improve
      outcomes in FL, extend the remission, postpone the need for chemotherapy and
      improve OS, maintenance therapies with rituximab and consolidation treatments
      represent very attractive strategies. (90)Y-ibritumomab tiuxetan ((90)Y-IT,
      Zevalin(r)) is approval as consolidation therapy in previously untreated FL
      patients who achieve response to first-line chemotherapy. Consolidation therapy
      with (90)Y-IT after initial induction treatment has shown improved activity
      compared with induction chemotherapy alone, even in patients previously treated
      with rituximab, in one phase III and several phase II trials, improving
      progression-free survival (PFS) and rate of conversion from partial response (PR)
      to complete response (CR). The phase III international FIT trial shows an
      improvement in PFS that is maintained after a median follow up of 7.3 years.
      Several phase II trials show high rate of conversion from PR to CR and a
      significant improvement in PFS. Treatment is feasible and well tolerated although
      myelodysplastic syndrome cases has been observed in some trials. (90)Y-IT should
      be considered for the initial treatment of FL in patients who are unable to
      tolerate standard chemotherapy, e.g., elderly or frail patients and otherwise in
      high-risk patients who achieve a PR or CR due to improvements in CR rate and PFS.

PMID- 24883179
TI  - The evolving role of FLT3 inhibitors in acute myeloid leukemia: quizartinib and
      beyond.
AB  - Acute myeloid leukemia remains associated with poor outcomes despite advances in
      our understanding of the complicated molecular events driving leukemogenesis and
      malignant progression. Those patients harboring mutations in the FLT3 receptor
      tyrosine kinase have a particularly poor prognosis; however, significant
      excitement has been generated by the emergence of a variety of targeted
      inhibitors capable of suppressing FLT3 signaling in vivo. Here we will review
      results from preclinical studies and early clinical trials evaluating both first-
      and second-generation FLT3 inhibitors. Early FLT3 inhibitors (including
      sunitinib, midostaurin, and lestaurtinib) demonstrated significant promise in
      preclinical models of FLT3 mutant AML. Unfortunately, many of these compounds
      failed to achieve robust and sustained FLT3 inhibition in early clinical trials,
      at best resulting in only transient decreases in peripheral blast counts. These
      results have prompted the development of second-generation FLT3 inhibitors,
      epitomized by the novel agent quizartinib. These second-generation inhibitors
      have demonstrated enhanced FLT3 specificity and have been generally well
      tolerated in early clinical trials. Several FLT3 inhibitors have reached phase
      III clinical trials, and a variety of phase I/II trials exploring a role for
      these novel compounds in conjunction with conventional chemotherapy or
      hematopoietic stem cell transplantation are ongoing. Finally, molecular insights
      provided by FLT3 inhibitors have shed light upon the variety of mechanisms
      underlying the acquisition of resistance and have provided a rationale supporting
      the use of combinatorial regimens with other emerging targeted therapies. 

PMID- 24883181
TI  - Lenalidomide in relapsed or refractory mantle cell lymphoma: overview and
      perspective.
AB  - Lenalidomide, a novel immunomodulatory agent, was approved by the US Food and
      Drug Administration for the treatment of myelodysplastic syndrome and relapsed
      multiple myeloma. Data from preclinical studies paved the way for clinical trials
      of lenalidomide in mantle cell lymphoma (MCL). Initial phase I and II clinical
      trials of lenalidomide alone and as part of combination regimens in patients with
      relapsed/refractory MCL have shown promising results. Its immunomodulatory, T
      cell costimulatory, anti-inflammatory and anti-angiogenic actions working
      together in the tumor cell microenvironment seem to be responsible for its
      enhanced antitumor efficacy. Lenalidomide's nature of action and safety profile
      favor it over other agents studied in relapsed/refractory MCL. This review
      summarizes the data from preclinical and clinical studies of lenalidomide in
      relapsed/refractory MCL and compares the results with those of other novel agents
      being used for relapsed/refractory MCL. 

PMID- 24883182
TI  - A Chemical Probe Targets DNA 5-Formylcytosine Sites and Inhibits TDG Excision,
      Polymerases Bypass, and Gene Expression.
AB  - Dynamic regulation and faithful maintenance of proper DNA methylation patterns
      are essential for many cellular functions. 5-Formylcytosine (5fC), a newly
      discovered oxidized form of methylcytosine (mC) is involved in active DNA
      demethylation process. The latest progresses suggest exciting novel functional
      roles of this residue. Chemical tools are desired to further elucidate the
      functional roles of 5fC and to modulate dynamics of DNA demethylation and
      downstream biological processes. Here we designed and constructed a chemical
      probe, consisting of an aldehyde targeting group and an intercalation group. This
      molecule can selectively react with 5fC and subsequently inhibit base excision by
      thymine DNA glycosylase (TDG) and cause significant pausing for both DNA and RNA
      polymerase elongation. Further investigation using a GFP reporter system in
      living cells revealed that the ligand modification in 5fC sites at 5'-UTR of the
      GFP gene greatly inhibited the GFP expression level. These results altogether
      confirmed our successful design and established a new approach for generating
      functional ligands that target the formylcytosine sites and modulate 5fC-related
      biological processes.

PMID- 24883183
TI  - Prevalence of nosocomial infections and anti-infective therapy in Benin: results
      of the first nationwide survey in 2012.
AB  - BACKGROUND: Data on nosocomial infections in hospitals in low-income countries
      are scarce and often inconsistent. The objectives of this study were to estimate
      the prevalence of nosocomial infections and antimicrobial drug use in Benin
      hospitals. METHODS: All hospitals were invited to participate in the first
      national point prevalence study conducted between 10-26 October 2012 using the
      protocol developed by the "Hospitals in Europe Link for Infection Control through
      Surveillance" (HELICS) project. Infection prevalence rates and the proportion of
      infected patients and exposure to antimicrobials were assessed. RESULTS: Overall,
      87% (39/45) of hospitals participated. Of 3130 inpatients surveyed, 972
      nosocomial infections were identified among 597 patients, representing an overall
      prevalence of infected patients of 19.1%. The most frequent infections were
      related to the urinary tract (48.2%), vascular catheter use (34.7%), and surgical
      site (24.7%). 64.6% of patients surveyed were treated with antibiotics, including
      a significant proportion (30%) of non-infected patients and a high proportion of
      self-medication (40.8%). Resistance of leading nosocomial pathogens to
      antimicrobials included methicillin-resistance (52.5%) among Staphylococcus
      aureus, vancomycin resistance among enterococci (67.5%), cefotaxime resistance
      among Escherichia coli (67.6%), and ceftazidime resistance among Acinetobacter
      baumannii (100%) and Pseudomonas aeruginosa (68.2%). CONCLUSIONS: Benin has high
      nosocomial infection rates and calls for the implementation of new national
      infection control policies. Patient safety education and training of all
      individuals involved in healthcare delivery will be critical to highlight
      awareness of the burden of disease. The high use of antimicrobials needs to be
      addressed, particularly their indiscriminate use in non-infected patients.

PMID- 24883185
TI  - The Amazon continuum dataset: quantitative metagenomic and metatranscriptomic
      inventories of the Amazon River plume, June 2010.
AB  - BACKGROUND: The Amazon River is by far the world's largest in terms of volume and
      area, generating a fluvial export that accounts for about a fifth of riverine
      input into the world's oceans. Marine microbial communities of the Western
      Tropical North Atlantic Ocean are strongly affected by the terrestrial materials
      carried by the Amazon plume, including dissolved (DOC) and particulate organic
      carbon (POC) and inorganic nutrients, with impacts on primary productivity and
      carbon sequestration. RESULTS: We inventoried genes and transcripts at six
      stations in the Amazon River plume during June 2010. At each station, internal
      standard-spiked metagenomes, non-selective metatranscriptomes, and poly(A)
      selective metatranscriptomes were obtained in duplicate for two discrete size
      fractions (0.2 to 2.0 MUm and 2.0 to 156 MUm) using 150 * 150 paired-end Illumina
      sequencing. Following quality control, the dataset contained 360 million reads of
      approximately 200 bp average size from Bacteria, Archaea, Eukarya, and viruses.
      Bacterial metagenomes and metatranscriptomes were dominated by Synechococcus,
      Prochlorococcus, SAR11, SAR116, and SAR86, with high contributions from SAR324
      and Verrucomicrobia at some stations. Diatoms, green picophytoplankton,
      dinoflagellates, haptophytes, and copepods dominated the eukaryotic genes and
      transcripts. Gene expression ratios differed by station, size fraction, and
      microbial group, with transcription levels varying over three orders of magnitude
      across taxa and environments. CONCLUSIONS: This first comprehensive inventory of
      microbial genes and transcripts, benchmarked with internal standards for full
      quantitation, is generating novel insights into biogeochemical processes of the
      Amazon plume and improving prediction of climate change impacts on the marine
      biosphere.

PMID- 24883184
TI  - Effect of Saccharomyces cerevisiae on alfalfa nutrient degradation
      characteristics and rumen microbial populations of steers fed diets with
      different concentrate-to-forage ratios.
AB  - Live yeast (Saccharomyces cerevisiae) constitutes an effective additive for
      animal production; its probiotic effect may be related to the concentrate-to
      forage ratio (CTFR). The objective of this study was to assess the effects of S.
      cerevisiae (SC) on fiber degradation and rumen microbial populations in steers
      fed diets with different levels of dietary concentrate. Ten Simmental * Local
      crossbred steers (450 +/- 50 kg BW) were assigned to a control group or an SC
      group. Both groups were fed the same basal diet but the SC group received SC
      supplementation (8 * 10(9) cfu/h/d through the ruminal fistula) following a two
      period crossover design. Each period consisted of four phases, each of which
      lasted 17 d: 10 d for dietary adaptation, 6 d for degradation study, and 1 d for
      rumen sample collection. From the 1(st) to the 4(th) phase, steers were fed in a
      stepwise fashion with increasing CTFRs, i.e., 30:70, 50:50, 70:30, and 90:10. The
      kinetics of dry matter and fiber degradation of alfalfa pellets were evaluated;
      the rumen microbial populations were detected using real-time PCR. The results
      revealed no significant (P > 0.05) interactions between dietary CTFR and SC for
      most parameters. Dietary CTFR had a significant effect (P < 0.01) on degradation
      characteristics of alfalfa pellets and the copies of rumen microorganism; the
      increasing concentrate level resulted in linear, quadratic or cubic variation
      trend for these parameters. SC supplementation significantly (P < 0.05) affected
      dry matter (DM) and neutral detergent fiber (NDF) degradation rates (c DM, c NDF)
      and NDF effective degradability (EDNDF). Compared with the control group, there
      was an increasing trend of rumen fungi and protozoa in SC group (P < 0.1); copies
      of total bacteria in SC group were significantly higher (P < 0.05). Additionally,
      percentage of Ruminobacter amylophilus was significantly lower (P < 0.05) but
      percentage of Selenomonas ruminantium was significantly higher (P < 0.05) in the
      SC group. In a word, dietary CTFR had a significant effect on degradation
      characteristics of forage and rumen microbial population. S. cerevisiae had
      positive effects on DM and NDF degradation rate or effective degradability of
      forage; S. cerevisiae increased rumen total bacteria, fungi, protozoa, and
      lactate-utilizing bacteria but reduced starch-degrading and lactate-producing
      bacteria. 

PMID- 24883186
TI  - ISMAR-study presentation: in-hospital epidemiology and clinical management of
      respiratory and cardiac comorbidities in cardiac and respiratory disease units.
AB  - BACKGROUND: Cardiovascular and respiratory diseases are leading causes of
      morbidity and their co-occurrence has important implications in mortality and
      other outcomes. Even the most recent guidelines do not reliably address clinical,
      prognostic, and therapeutic concerns due to the overlap of respiratory and
      cardiac diseases. STUDY OBJECTIVES AND DESIGN: In order to evaluate in the
      reality of clinical practice the epidemiology and the reciprocal impact of cardio
      pulmonary comorbidity on the clinical management, diagnostic workup and
      treatment, 1,500 cardiac and 1,500 respiratory inpatients, admitted in acute and
      rehabilitation units, will be enrolled in a multicenter, nationwide, prospective
      observational study. For this purpose, each center will enroll at least 50
      consecutive patients. At discharge, data analysis will be aimed at the definition
      of cardiac and pulmonary inpatient comorbidity prevalence, demographic
      characteristics, length of hospital stay, and risk factors, taking into account
      also procedures, pharmacological and non-pharmacological treatment, and follow up
      in patients with cardio-respiratory comorbidity. CONCLUSIONS: The purely
      observational design of the study aims to give new relevant information on the
      assessment and management of overlapping patients in real life clinical practice,
      and new insight for improvement and implementation of current guidelines on the
      management of individual diseases.

PMID- 24883188
TI  - Multifunctional Chitosan Magnetic-Graphene (CMG) Nanoparticles: a Theranostic
      Platform for Tumor-targeted Co-delivery of Drugs, Genes and MRI Contrast Agents.
AB  - Combing chemotherapy with gene therapy has been one of the most promising
      strategies for the treatment of cancer. The noninvasive MRI with
      superparamagnetic iron oxide (SPIO) as contrast agent is one of the most
      effecitve techniques for evaluating the antitumor therapy. However, to construct
      a single system that can deliver efficiently gene, drug and SPIO to the cancer
      site remains a challenge. Herein, we report a chitosan functionalized magnetic
      graphene nanoparticle (CMG) platform for simultaneous gene/drug and SPIO delivery
      to tumor. The phantom and ex vivo MRI images suggest CMG as a strong T2 contrast
      enhancing agent. The CMGs are biocompatible as evaluated by the WST assay and
      predominantly accumulate in tumors as shown by biodistribution studies and MRI.
      The anticancer drug doxorubicin (DOX) loaded CMGs (DOX-CMGs) release DOX faster
      at pH 5.1 than at pH 7.4, and more effective (IC50 = 2 MUM) in killing A549 lung
      cancer cells than free DOX (IC50 = 4 MUM). CMGs efficiently deliver DNA into A549
      lung cancer cells and C42b prostate cancer cells. In addition, i.v.
      administration of GFP-plasmid encapsulated within DOX-CMGs into tumor-bearing
      mice has showed both GFP expression and DOX accumulation at the tumor site at 24
      and 48 hrs after administration. These results indicate CMGs provide a robust and
      safe theranostic platform, which integrates targeted delivery of both gene
      medicine and chemotherapeutic drug(s), and enhanced MR imaging of tumors. The
      integrated chemo- and gene- therapeutic and diagnostic design of CMG
      nanoparticles shows promise for simultaneous targeted imaging, drug delivery and
      real -time monitoring of therapeutic effect for cancer.

PMID- 24883189
TI  - Cytokine responsiveness of CD8(+) T cells is a reproducible biomarker for the
      clinical efficacy of dendritic cell vaccination in glioblastoma patients.
AB  - BACKGROUND: Immunotherapeutic approaches, such as dendritic cell (DC)
      vaccination, have emerged as promising strategies in the treatment of
      glioblastoma. Despite their promise, however, the absence of objective biomarkers
      and/or immunological monitoring techniques to assess the clinical efficacy of
      immunotherapy still remains a primary limitation. To address this, we sought to
      identify a functional biomarker for anti-tumor immune responsiveness associated
      with extended survival in glioblastoma patients undergoing DC vaccination.
      METHODS: 28 patients were enrolled and treated in two different Phase 1 DC
      vaccination clinical trials at UCLA. To assess the anti-tumor immune response
      elicited by therapy, we studied the functional responsiveness of pre- and post
      vaccination peripheral blood lymphocytes (PBLs) to the immunostimulatory
      cytokines interferon-gamma (IFN-gamma) and interleukin-2 (IL-2) in 21 of these
      patients for whom we had adequate material. Immune responsiveness was quantified
      by measuring downstream phosphorylation events of the transcription factors, STAT
      1 and STAT-5, via phospho-specific flow cytometry. RESULTS: DC vaccination
      induced a significant decrease in the half-maximal concentration (EC-50) of IL-2
      required to upregulate pSTAT-5 specifically in CD3(+)CD8(+) T lymphocytes (p <
      0.045). Extended survival was also associated with an increased per cell
      phosphorylation of STAT-5 in cytotoxic T-cells following IL-2 stimulation when
      the median post/pre pSTAT-5 ratio was used to dichotomize the patients (p =
      0.0015, log-rank survival; hazard ratio = 0.1834, p = 0.018). Patients whose
      survival was longer than two years had a significantly greater pSTAT-5 ratio (p =
      0.015), but, contrary to our expectations, a significantly lower pSTAT-1 ratio (p
      = 0.038). CONCLUSIONS: Our results suggest that monitoring the pSTAT signaling
      changes in PBL may provide a functional immune monitoring measure predictive of
      clinical efficacy in DC-vaccinated patients.

PMID- 24883190
TI  - Tumor immunology and cancer immunotherapy: summary of the 2013 SITC primer.
AB  - Knowledge of the basic mechanisms of the immune system as it relates to cancer
      has been increasing rapidly. These developments have accelerated the translation
      of these advancements into medical breakthroughs for many cancer patients. The
      immune system is designed to discriminate between self and non-self, and through
      genetic recombination there is virtually no limit to the number of antigens it
      can recognize. Thus, mutational events, translocations, and other genetic
      abnormalities within cancer cells may be distinguished as "altered-self" and
      these differences may play an important role in preventing the development or
      progression of cancer. However, tumors may utilize a variety of mechanisms to
      evade the immune system as well. Cancer biologists are aiming to both better
      understand the relationship between tumors and the normal immune system, and to
      look for ways to alter the playing field for cancer immunotherapy. Summarized in
      this review are discussions from the 2013 SITC Primer, which focused on reviewing
      current knowledge and future directions of research related to tumor immunology
      and cancer immunotherapy, including sessions on innate immunity, adaptive
      immunity, therapeutic approaches (dendritic cells, adoptive T cell therapy, anti
      tumor antibodies, cancer vaccines, and immune checkpoint blockade), challenges to
      driving an anti-tumor immune response, monitoring immune responses, and the
      future of immunotherapy clinical trial design. 

PMID- 24883192
TI  - (226)Ra, (232)Th and (40)K contents in water samples in part of central deserts
      in Iran and their potential radiological risk to human population.
AB  - BACKGROUND: The radiological quality of (226)Ra, (232)Th and (40)K in some
      samples of water resources collected in Anarak-Khour a desertic area, Iran has
      been measured by direct gamma ray spectroscopy using high purity germanium
      detector in this paper. RESULT: The concentration ranged from <=0.5 to 9701 mBq/L
      for (226)Ra; <=0.2 to 28215 mBq/L for (232)Th and < MDA to 10332 mBq/L for (40)K.
      The radium equivalent activity was well below the defined limit of 370Bq/L. The
      calculated external hazard indices were found to be less than 1 which shows a low
      dose. CONCLUSION: These results can be contributed to the database of this area
      because it may be used as disposal sites of nuclear waste in future.

PMID- 24883191
TI  - Sex and age-related differences in performance in a 24-hour ultra-cycling draft
      legal event - a cross-sectional data analysis.
AB  - BACKGROUND: The purpose of this study was to examine the sex and age-related
      differences in performance in a draft-legal ultra-cycling event. METHODS: Age
      related changes in performance across years were investigated in the 24-hour
      draft-legal cycling event held in Schotz, Switzerland, between 2000 and 2011
      using multi-level regression analyses including age, repeated participation and
      environmental temperatures as co-variables. RESULTS: For all finishers, the age
      of peak cycling performance decreased significantly (beta = -0.273, p = 0.036)
      from 38 +/- 10 to 35 +/- 6 years in females but remained unchanged (beta = 
      0.035, p = 0.906) at 41.0 +/- 10.3 years in males. For the annual fastest females
      and males, the age of peak cycling performance remained unchanged at 37.3 +/- 8.5
      and 38.3 +/- 5.4 years, respectively. For all female and male finishers, males
      improved significantly (beta = 7.010, p = 0.006) the cycling distance from 497.8
      +/- 219.6 km to 546.7 +/- 205.0 km whereas females (beta = -0.085, p = 0.987)
      showed an unchanged performance of 593.7 +/- 132.3 km. The mean cycling distance
      achieved by the male winners of 960.5 +/- 51.9 km was significantly (p < 0.001)
      greater than the distance covered by the female winners with 769.7 +/- 65.7 km
      but was not different between the sexes (p > 0.05). The sex difference in
      performance for the annual winners of 19.7 +/- 7.8% remained unchanged across
      years (p > 0.05). The achieved cycling distance decreased in a curvilinear manner
      with advancing age. There was a significant age effect (F = 28.4, p < 0.0001) for
      cycling performance where the fastest cyclists were in age group 35-39 years.
      CONCLUSION: In this 24-h cycling draft-legal event, performance in females
      remained unchanged while their age of peak cycling performance decreased and
      performance in males improved while their age of peak cycling performance
      remained unchanged. The annual fastest females and males were 37.3 +/- 8.5 and
      38.3 +/- 5.4 years old, respectively. The sex difference for the fastest
      finishers was ~20%. It seems that women were not able to profit from drafting to
      improve their ultra-cycling performance.

PMID- 24883193
TI  - Synthesis and characterization of molecularly imprinted polymers for the
      remediation of PCBs and dioxins in aqueous environments.
AB  - This paper, reports on the approach devised to remediate water sources
      contaminated with PCBs and dioxins. The approach reported is based on the
      synthesis of highly selective molecularly imprinted polymers (MIPs). The paper
      elaborates the materials, procedures and protocols devised and followed for the
      synthesis of MIPs. The characterization of the synthesized MIPs and NIPs were
      performed using a number of techniques, such as FTIR, SEM, etc. The FTIR results
      show a broad OH stretching vibration peaks associated with methacrylic acid
      carboxylic group (COOH). at 3710 cm(-1) for NIP and 3588 cm(-1) for MIP, -CH2
      stretching peak at 2953 cm(-1)for NIP, peaks due to the presence of methylene
      group in both MAA and EDMA appearing at 2951 cm(-1) for MIP. The carbonyl group C
      = O stretching peak was observed in both MIP and NIP at 1721 cm(-1) and this
      might have originated from MAA and EDMA respectively in both MIP and NIP. Weak
      combination bands from 1637 cm(-1) to 1249 cm(-1) and sharp bands at 1143 cm(-1)
      specifically on MIPs spectra indicated the presence of aromatic ring of the
      template. The surface area of MIP was found to be 74.0010 m(2)/g, thus larger
      than that for NIP which was 58.6519 m(2)/g due to the presence of cavities on
      MIPs. The fit of the Langmuir model was found to be r (2) = 0.5842 while
      Freundlich model were found to be r(2) = 0.3241, signifying that better
      correlation was with Langmuir than Freundlich. 

PMID- 24883194
TI  - Production of recombinant antibodies using bacteriophages.
AB  - Recombinant antibody fragments such as Fab, scFv, diabodies, triabodies, single
      domain antibodies and minibodies have recently emerged as potential alternatives
      to monoclonal antibodies, which can be engineered using phage display technology.
      These antibodies match the strengths of conventionally produced monoclonal
      antibodies and offer advantages for the development of immunodiagnostic kits and
      assays. These fragments not only retain the specificity of the whole monoclonal
      antibodies but also easy to express and produce in prokaryotic expression system.
      Further, these antibody fragments are genetically stable, less expensive, easy to
      modify in response to viral mutations and safer than monoclonal antibodies for
      use in diagnostic and therapeutic applications. This review describes the
      potential of antibody fragments generated using phage display and their use as
      diagnostic reagents. 

PMID- 24883195
TI  - Difficulties in species identification within the genus Haemophilus - A pilot
      study addressing a significant problem for routine diagnostics.
AB  - Diagnostic misidentifications of commensalic Haemophilus haemolyticus as
      pathogenic Haemophilus influenzae are frequent. This pilot study evaluates
      whether isolations of H. haemolyticus are frequent enough in Germany to cause a
      relevant diagnostic problem, considering the fact that even H. influenzae is a
      mere colonizer in about 30% of isolations. In microbiological laboratories of two
      hospitals located in Northern and Southern Germany, the distribution of
      Haemophilus spp. was analyzed during a six-month-period. Site of infection, sex,
      and age of the patients was taken into consideration. A total of 77 Haemophilus
      spp. isolates was acquired and discriminated on species level, comprising: 48 H.
      influenzae, 25 Haemophilus parainfluenzae, 3 H. haemolyticus, and 1 Haemophilus
      parahaemolyticus. The proportion of H. haemolyticus was calculated to range
      between 1.2% and 16.2 % within the 95% confidence limits. Commensalic Haemophilus
      spp. were isolated from oropharynx-associated sites only. H. influenzae, in
      contrast, was detected in clinically relevant materials like lower respiratory
      materials and conjunctiva swabs. Altogether, there was a low proportion of
      clinical H. haemolyticus isolates. Accordingly, the problem of unnecessary
      antibiotic therapies due to misidentifications of H. haemolyticus as H.
      influenzae is quantitatively negligible compared with the risk of confusing H.
      influenzae colonizations with infections. 

PMID- 24883196
TI  - rpsU-based discrimination within the genus Burkholderia.
AB  - Sequencing of the gene rpsU reliably delineates saprophytic Burkholderia (B.)
      thailandensis from highly pathogenic B. mallei and B. pseudomallei. We analyzed
      the suitability of this technique for the delineation of the B. pseudomallei
      complex from other Burkholderia species. Both newly recorded and previously
      deposited sequences of well-characterized or reference strains (n = 84) of
      Azoarcus spp., B. ambifaria, B. anthina, B. caledonica, B. caribensis, B.
      caryophylli, B. cenocepacia, B. cepacia, B. cocovenenans, B. dolosa, B. fungorum,
      B. gladioli, B. glathei, B. glumae, B. graminis, B. hospita, B. kururensis, B.
      mallei, B. multivorans, B. phenazinium, B. phenoliruptrix, B. phymatum, B.
      phytofirmans, B. plantarii, B. pseudomallei, B. pyrrocinia, B. stabilis, B.
      thailandensis, B. ubonensis, B. vietnamiensis, B. xenovorans, not further defined
      Burkholderia spp., and the outliers Cupriavidus metallidurans, Laribacter
      hongkongensis, Pandorea norimbergensis, and Ralstonia pickettii were included in
      a multiple sequence analysis. Multiple sequence alignments led to the delineation
      of four major clusters, rpsU-I to rpsU-IV, with a sequence homology >92%. The B.
      pseudomallei complex formed the complex rpsU-II. Several Burkholderia species
      showed 100% sequence homology. This procedure is useful for the molecular
      confirmation or exclusion of glanders or melioidosis from primary patient
      material. Further discrimination within the Burkholderia genus requires other
      molecular approaches. 

PMID- 24883197
TI  - Miscarriage history and Toxoplasma gondii infection: A cross-sectional study in
      women in Durango City, Mexico.
AB  - Through a cross-sectional study design, 326 women with a history of miscarriage
      were examined for anti-Toxoplasma gondii IgG and IgM antibodies in Durango City,
      Mexico. Prevalence association with sociodemographic, clinical, and behavioral
      characteristics in women with miscarriage was also investigated. Twenty-two
      (6.7%) of the 326 women studied had anti-T. gondii IgG antibodies and two (0.6%)
      were also positive for anti-T. gondii IgM antibodies. Seroprevalence of T. gondii
      infection was not influenced by age, birth place, occupation, educational level,
      or socioeconomic status. In contrast, logistic regression showed that T. gondii
      exposure was associated with consumption of raw or undercooked meat (OR = 6.84;
      95% CI: 1.04-44.95; P = 0.04) and consumption of chicken brains (OR = 18.48; 95%
      CI: 1.26-269.43; P = 0.03). This is the first study on the seroepidemiology of T.
      gondii infection in women with a history of miscarriage in Northern Mexico. Of
      interest, we also observed an association of T. gondii exposure with consumption
      of chicken brains. Contributing factors for T. gondii exposure found in the
      present study should be taken into consideration for public health measures to
      avoid infection with T. gondii and its sequelae. 

PMID- 24883198
TI  - Evaluation of immune responses by live infectious bursal disease vaccines to
      avoid vaccination failures.
AB  - Infectious Bursal Disease (IBD) is a viral, contagious immunosuppressive disease
      posing an important threat to the commercial poultry industry. Evolution of
      highly virulent strains of IBD virus warranted the need for detailed
      characterization of the immune responses offered by the currently available
      vaccines. Two extensively used live vaccines of varied attenuation levels -
      intermediate and intermediate plus - strains were analyzed for the induction of
      immune responses. Both the vaccines induced protective antibody titers with the
      onset, quicker and higher with the intermediate plus vaccine. The intermediate
      plus strain vaccinate was observed to induce higher levels of IFN-gamma in the
      birds. These results were supported by immunophenotype analyses with an increase
      in CD8+ and simultaneous decrease in CD4+ cell population. Both vaccine strains
      conferred protective immunity against virulent challenge. The study warrants the
      use of intermediate plus vaccines in disease endemic regions and intermediate
      vaccines in non-endemic regions to prevent IBD infection. 

PMID- 24883199
TI  - Administration of a nondepleting anti-CD25 monoclonal antibody reduces disease
      severity in mice infected with Trypanosoma cruzi.
AB  - The role of CD25+ regulatory T cells during the course of Trypanosoma cruzi
      infection has been previously analyzed, and the bulk of results have shown a
      limited role for this T cell subpopulation. In this study, we have used an IgM,
      nondepleting monoclonal antibody (mAb) aiming at blocking interleukin (IL)-2
      activity on CD25+ T cells. The administration of this antibody 10 days before
      infection increased the resistance of outbred Swiss mice to the Colombian strain
      of T. cruzi. Anti-CD25-treated mice had lower parasitemia and augmented numbers
      of effector memory T cells. In addition, these animals showed higher numbers of
      splenic T cells secreting IFN-gamma and TNF-alpha, both cytokines described to be
      involved in the resistance to T. cruzi infection. The same treatment also
      increased the numbers of splenic T cells that produced homeostatic and regulatory
      cytokines, such as IL-2 and IL-10, and CD4+CD25+ T cells. The administration of
      nondepleting anti-CD25 mAb at the beginning of the chronic phase, when parasites
      were cleared from the blood, halted the inflammatory process in the heart,
      without any signs of infection reactivation. These results indicate that
      nondepleting anti-CD25 monoclonal antibodies may be useful to treat chronic
      Chagas' disease. 

PMID- 24883200
TI  - Erythrocyte and blood antibacterial defense.
AB  - It is an axiom that blood cellular immunity is provided by leukocytes. As to
      erythrocytes, it is generally accepted that their main function is respiration.
      Our research provides objective video and photo evidence regarding erythrocyte
      bactericidal function. Phase-contrast immersion vital microscopy of the blood of
      patients with bacteremia was performed, and the process of bacteria entrapping
      and killing by erythrocytes was shot by means of video camera. Video evidence
      demonstrates that human erythrocytes take active part in blood bactericidal
      action and can repeatedly engulf and kill bacteria of different species and size.
      Erythrocytes are extremely important integral part of human blood cellular
      immunity. COMPARED WITH PHAGOCYTIC LEUKOCYTES, THE ERYTHROCYTES: a) are more
      numerous; b) are able to entrap and kill microorganisms repeatedly without being
      injured; c) are more resistant to infection and better withstand the attacks of
      pathogens; d) have longer life span and are produced faster; e) are inauspicious
      media for proliferation of microbes and do not support replication of chlamidiae,
      mycoplasmas, rickettsiae, viruses, etc.; and f) are more effective and
      uncompromised bacterial killers. Blood cellular immunity theory and traditional
      view regarding the function of erythrocytes in human blood should be revised.

PMID- 24883201
TI  - A selective IgA deficiency in a boy who presented recurrent parotitis.
AB  - Recurrent parotitis is a non-obstructive, non-suppurative inflammatory disease
      which is characterized by unilateral or bilateral parotid gland swelling attacks.
      It is also known as juvenile recurrent parotitis. Although the etiology is
      unknown, congenital malformations of the ductus, genetic predisposition,
      infections, allergies, autoimmune diseases, and some immune deficiencies are
      blamed. Here, we present a case report of recurrent parotitis with selective
      immunoglobulin A deficiency in a six-year-old boy. The patient was presented to
      us with a new episode of swelling of left parotid region. In the last 2 years,
      the patient suffered from recurrent parotitis which lasted for approximately 5
      days in ten individual episodes. 

PMID- 24883202
TI  - Anemia control in kidney transplant recipients using once-monthly continuous
      erythropoietin receptor activator: a prospective, observational study.
AB  - In a multicenter, prospective, observational study of 279 kidney transplant
      recipients with anemia, the efficacy and safety of once-monthly continuous
      erythropoietin receptor activator (C.E.R.A.) were assessed to a maximum of 15
      months. The main efficacy variable was the proportion of patients achieving a
      hemoglobin level of 11-12 g/dL at each of visits between months 7 and 9. At study
      entry, 224 patients (80.3%) were receiving erythropoiesis stimulating agent (ESA)
      therapy including darbepoetin alfa (98), epoetin beta (61), and C.E.R.A. (45).
      The mean (SD) time between C.E.R.A. applications was 34.0 (11.9) days. Among 193
      patients for whom efficacy data were available, mean (SD) hemoglobin was 11.1
      (0.99) g/dL at study entry, 11.5 (1.1) g/dL at month 7, 11.6 (1.3) g/dL at month
      9, and 11.4 (1.1) g/dL at month 15. During months 7-9, 20.7% of patients had all
      hemoglobin values within the range 11-12 g/dL and 64.8% were within 10-13 g/dL.
      Seven patients (2.5%) discontinued C.E.R.A. due to adverse events or serious
      adverse events. In this observational trial under real-life conditions, once
      monthly C.E.R.A. therapy achieved stable hemoglobin levels in stable kidney
      transplant recipients with good tolerability, and with no requirement for any
      dose change in 43% of patients. 

PMID- 24883203
TI  - Using eye tracking to assess reading performance in patients with glaucoma: a
      within-person study.
AB  - Reading is often cited as a demanding task for patients with glaucomatous visual
      field (VF) loss, yet reading speed varies widely between patients and does not
      appear to be predicted by standard visual function measures. This within-person
      study aimed to investigate reading duration and eye movements when reading short
      passages of text in a patient's worse eye (most VF damage) when compared to their
      better eye (least VF damage). Reading duration and saccade rate were
      significantly different on average in the worse eye when compared to the better
      eye (P < 0.001) in 14 patients with glaucoma that had median (interquartile
      range) between-eye difference in mean deviation (MD; a standard clinical measure
      for VF loss) of 9.8 (8.3 to 14.8) dB; differences were not related to the size of
      the difference in MD between eyes. Patients with a more pronounced effect of
      longer reading duration on their worse eye made a larger proportion of
      "regressions" (backward saccades) and "unknown" EMs (not adhering to expected
      reading patterns) when reading with the worse eye when compared to the better
      eye. A between-eye study in patients with asymmetric disease, coupled with eye
      tracking, provides a useful experimental design for exploring reading performance
      in glaucoma. 

PMID- 24883204
TI  - Surgery for complete vertical rectus paralysis combined with horizontal
      strabismus.
AB  - Aims. To report outcomes of the simultaneous surgical correction of vertical
      rectus paralysis combined with moderate-to-large angle horizontal strabismus.
      Methods. If a preoperative forced duction test was positive, antagonist muscle
      weakening surgery was performed, and then augmented partial rectus muscle
      transposition (APRMT) + partial horizontal rectus recession-resection was
      performed 2 months later. If a preoperative forced duction test was negative,
      APRMT + partial horizontal rectus recession-resection was performed. Antagonistic
      muscle weakening surgery and/or conventional recession-resection of the
      horizontal and/or vertical muscles of the contralateral eye was performed 2
      months later, as needed. Results. Ten patients with a mean age of 22.3 +/- 13.0
      years were included and mean follow-up was 7.1 months. The mean vertical
      deviation that APRMT corrected was 21.4 +/- 3.7 PD (prism diopter). The absolute
      deviation in horizontal significantly decreased from a preoperative value of 48.5
      +/- 27.4 PD to a value of 3.0 +/- 2.3 PD 6 months postoperatively. The movement
      score decreased from a value of -5 +/- 0 preoperatively to a value of -2.7 +/-
      0.8 at 6 months postoperatively. Conclusion. For patients with complete vertical
      rectus paralysis combined with a moderate- to-large angle of horizontal
      strabismus, combined APRMT and partial horizontal rectus recession-resection is
      safe and effective for correcting vertical and horizontal strabismus. 

PMID- 24883206
TI  - Outcome measures in multiple sclerosis.

PMID- 24883205
TI  - Outcome measures in relapsing-remitting multiple sclerosis: capturing disability
      and disease progression in clinical trials.
AB  - Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease
      that manifests as acute relapses and progressive disability. As a primary
      endpoint for clinical trials in MS, disability is difficult to both characterize
      and measure. Furthermore, the recovery from relapses and the rate of disability
      vary considerably among patients. Given these challenges, investigators have
      developed and studied the performance of various outcome measures and surrogate
      endpoints in MS clinical trials. This review defines the outcome measures and
      surrogate endpoints used to date in MS clinical trials and presents challenges in
      the design of both adult and pediatric trials. 

PMID- 24883207
TI  - Revisiting the role of first trimester homocysteine as an index of maternal and
      fetal outcome.
AB  - AIM. To revisit the role of first trimester homocysteine levels with the maternal
      and fetal outcome. METHODS. This was a cohort study comprising 100 antenatal
      women between 8 and 12 weeks of gestation. Serum homocysteine levels were checked
      after overnight fasting. RESULTS. There were significantly elevated homocysteine
      levels among women with prior history of hypertensive disorders of pregnancy and
      prior second or third trimester pregnancy losses. There was no significant
      difference in homocysteine levels among women with previous gestational diabetes
      mellitus, preterm deliveries, or fetal malformations. Homocysteine levels were
      significantly elevated in those who developed hypertensive disorder of pregnancy,
      oligohydramnios, and meconium stained amniotic fluid, had a pregnancy loss, or
      delivered a low birth weight baby. There was no significant difference in
      homocysteine levels for those who developed gestational diabetes mellitus.
      CONCLUSIONS. Increased first trimester serum homocysteine is associated with
      history of pregnancy losses, hypertensive disorders of pregnancy, and preterm
      birth. This is also associated with hypertensive disorders of pregnancy,
      pregnancy loss, oligohydramnios, meconium stained amniotic fluid, and low birth
      weight in the current pregnancy. This trial is registered with ClinicalTrials.gov
      CTRI/2013/02/003441.

PMID- 24883208
TI  - Drug utilization study in medical emergency unit of a tertiary care hospital in
      north India.
AB  - Objective. To generate data on the drug utilization pattern and cost of drug
      treatment and to determine the rationality of prescriptions. Methods. A
      retrospective cross-sectional drug utilization study was conducted in the medical
      emergency unit of our hospital. Patient case records were reviewed to extract
      data on the pattern of drug use. Cost of drug treatment for the emergency visit
      was calculated by referring to the cost mentioned in Monthly Index of Medical
      Specialties and the rationality of prescriptions was evaluated using WHO core
      indicators of drug utilization. Results. 1100 case records were reviewed.
      Majority of patients received proton pump inhibitors followed by multivitamins.
      The median cost per prescription was 119.23$ (7.32$-7663.46$). Majority (49.9%)
      of drug cost was driven by antibiotics alone. An average of 4.9 drugs was
      prescribed per prescription. There were 14.89% encounters with antibiotics.
      75.17% of the drugs were given as injectables and only 29.27% of the drugs were
      prescribed as generics. Conclusion. There is need to rationalize the drug therapy
      in terms of increasing prescribing of drugs by generic name and to avoid overuse
      of PPIs and multivitamins in emergency unit. Also the hospital pharmacy should be
      encouraged to procure more cost effective alternative antibiotics in future. 

PMID- 24883209
TI  - Treatment patterns in patients with metastatic melanoma: a retrospective
      analysis.
AB  - Objective. To describe treatment patterns and factors influencing treatment in a
      real-world setting of US patients with metastatic melanoma (MM). Methods. This
      was a retrospective claims-based study among patients with MM diagnosed between
      2005 and 2010 identified from MarketScan databases. Results. Of 2546 MM patients,
      66.8% received surgery, 44.7% received radiation, 38.7% received systemic
      therapies, and 17.7% received all modalities. Patients with lung, brain, liver,
      or bone metastases were less likely to undergo surgery (all P < 0.0001); patients
      with lung (P = 0.04), brain (P < 0.001), or liver metastases (P = 0.03) were more
      likely to receive systemic therapies; patients with brain (P < 0.0001) or bone
      metastases (P < 0.0001) were more likely to receive radiation therapy.
      Oncologists were more likely to recommend systemic therapy (P < 0.0001) or
      radiation (P < 0.0001), while dermatologists were more likely to recommend
      surgery (P = 0.002). Monotherapy was the dominant systemic therapy (82.4%
      patients as first-line). Conclusions. Only 39% of MM patients received systemic
      therapies, perhaps reflecting efficacy and safety limitations of conventional
      systemic therapies for MM. Among those receiving systemic therapy, monotherapy
      was the most common approach. Sites of metastases and physician speciality
      influenced treatment patterns. This study serves as a baseline against which
      future treatment pattern studies, following approval of new agents, can be
      compared. 

PMID- 24883211
TI  - Algae oil: a sustainable renewable fuel of future.
AB  - A nonrenewable fuel like petroleum has been used from centuries and its usage has
      kept on increasing day by day. This also contributes to increased production of
      greenhouse gases contributing towards global issues like global warming. In order
      to meet environmental and economic sustainability, renewable, carbon neutral
      transport fuels are necessary. To meet these demands microalgae are the key
      source for production of biodiesel. These microalgae do produce oil from sunlight
      like plants but in a much more efficient manner. Biodiesel provides more
      environmental benefits, and being a renewable resource it has gained lot of
      attraction. However, the main obstacle to commercialization of biodiesel is its
      cost and feasibility. Biodiesel is usually used by blending with petro diesel,
      but it can also be used in pure form. Biodiesel is a sustainable fuel, as it is
      available throughout the year and can run any engine. It will satisfy the needs
      of the future generation to come. It will meet the demands of the future
      generation to come. 

PMID- 24883210
TI  - Interaction Study of an Amorphous Solid Dispersion of Cyclosporin A in Poly-Alpha
      Cyclodextrin with Model Membranes by (1)H-, (2)H-, (31)P-NMR and Electron Spin
      Resonance.
AB  - The properties of an amorphous solid dispersion of cyclosporine A (ASD) prepared
      with the copolymer alpha cyclodextrin (POLYA) and cyclosporine A (CYSP) were
      investigated by (1)H-NMR in solution and its membrane interactions were studied
      by (1)H-NMR in small unilamellar vesicles and by (31)P (2)H NMR in phospholipidic
      dispersions of DMPC (dimyristoylphosphatidylcholine) in comparison with those of
      POLYA and CYSP alone. (1)H-NMR chemical shift variations showed that CYSP really
      interacts with POLYA, with possible adduct formation, dispersion in the solid
      matrix of the POLYA, and also complex formation. A coarse approach to the latter
      mechanism was tested using the continuous variations method, indicating an
      apparent 1 : 1 stoichiometry. Calculations gave an apparent association constant
      of log Ka = 4.5. A study of the interactions with phospholipidic dispersions of
      DMPC showed that only limited interactions occurred at the polar head group level
      ((31)P). Conversely, by comparison with the expected chain rigidification induced
      by CYSP, POLYA induced an increase in the fluidity of the layer while ASD
      formation led to these effects almost being overcome at 298 K. At higher
      temperature, while the effect of CYSP seems to vanish, a resulting global
      increase in chain fluidity was found in the presence of ASD. 

PMID- 24883214
TI  - Spinocerebellar Ataxia 7: A Report of Unaffected Siblings Who Married into
      Different SCA 7 Families.
AB  - Two families with spinocerebellar ataxia type 7 are presented. Although there are
      affected cousins, it is not the sibling parents that transmitted the mutation. It
      is assumed that the affected families share a common ancestor. 

PMID- 24883215
TI  - Maternal and Fetal Death following Group A Streptococcal Meningitis in Mid-Term
      Pregnancy.
AB  - Background. Group A streptococcal (GAS) meningitis is rarely seen in the
      antenatal period, but it is associated with significant mortality. We present a
      case of a mid-trimester woman who developed fulminant meningitis following a
      rapid onset atypical presentation of infection with this organism. Case. A
      multiparous 23(+5)-week woman presented with a 10-day history of a non-productive
      cough associated with pyrexia. Within minutes of her admission she collapsed and
      lost consciousness; sepsis was suspected and cross-specialty care was initiated.
      She was managed empirically in extremis with broad-spectrum antibiotics and
      mannitol with 3% hypertonic saline for suspected infection and raised
      intracranial pressure, respectively. Despite intensivist management, a CT head
      revealed diffuse oedema with coning of the cerebellar tonsils. Brainstem death
      was certified within 19 hours of admission and fetal death ensued. Postmortem
      bacteriology confirmed GAS meningitis. Conclusion. Through raising awareness of
      this patient and her disease course, we hope that future policy decisions,
      primary care, and hospital level management will be informed accordingly for
      treatment of pregnant women with suspected GAS infection. 

PMID- 24883212
TI  - Adult neuroplasticity: more than 40 years of research.
AB  - Within the last four decades, our view of the mature vertebrate brain has changed
      significantly. Today it is generally accepted that the adult brain is far from
      being fixed. A number of factors such as stress, adrenal and gonadal hormones,
      neurotransmitters, growth factors, certain drugs, environmental stimulation,
      learning, and aging change neuronal structures and functions. The processes that
      these factors may induce are morphological alterations in brain areas, changes in
      neuron morphology, network alterations including changes in neuronal
      connectivity, the generation of new neurons (neurogenesis), and neurobiochemical
      changes. Here we review several aspects of neuroplasticity and discuss the
      functional implications of the neuroplastic capacities of the adult and
      differentiated brain with reference to the history of their discovery. 

PMID- 24883216
TI  - Successful Pregnancy in a Patient with Combined Deficiency of Factor V and Factor
      VIII.
AB  - Inherited combined factor V and factor VIII deficiency (F5F8D) is autosomal
      recessive transmission disorder. Epistaxis, postsurgical bleeding, and
      menorrhagia are the most common symptoms. The risk of miscarriage and placental
      abruption is consequent. We report a case of successful pregnancy in a patient
      with F5F8D. 20-year-old woman, born of consanguineous parents, third gestate,
      first parity, two miscarriages, admitted for child birth of a spontaneous
      pregnancy estimated at 38 weeks and was diagnosed with F5F8D. At admission,
      patient was hemodynamically stable, with good obstetric conditions. The biologic
      results showed low levels of PT (52%), factor V (7%), and factor VIII (5%), and
      the activated partial thromboplastin time was prolonged (68,6%). Parturient was
      admitted in intensive care unit, maternal and fetal monitoring was performed.
      Fresh frozen plasma (FFP) and factor VIII concentrates were perfused at the
      induction of labor. Analgesia used fentanyl titration. The delivery gave birth to
      a newborn male, with Apgar 10/10 and 3000 g. The puerperium was simple without
      any important bleeding. Laboratory tests for the newborn were acceptable. Little
      literature is available on this subject and there are no guidelines available
      concerning pregnancy; we chose to prescribe a combination of factor VIII
      concentrate and FFP in pre-, per- and postpartum. The same protocol was
      successfully used in a patient before dental extraction and prostatectomy.
      Vaginal delivery is possible, as our case. Management by multidisciplinary team
      is recommended. 

PMID- 24883217
TI  - Blinding bilateral hyperviscosity retinopathy in a 43-year-old nigerian male with
      lymphoplasmacytic lymphoma: a case report and management challenges.
AB  - Lymphoplasmacytic lymphomas are rare and may present with uncommon and
      devastating symptoms. We report a case of a 43-year-old male who presented with
      bleeding gums and sudden onset of bilateral blindness but was not on
      anticoagulants and had no family history of bleeding disorder. He had bilateral
      hyperpigmented infraorbital skin lesions, visual acuities (VA) of hand motion in
      both eyes (blindness), round and sluggish pupils, and bilateral diffuse and
      extensive retinal haemorrhages obliterating the retinal details with central
      visual field defects. The optical coherence tomography revealed retinal
      haemorrhage, oedema, detachment, and diffuse photoreceptors damage.
      Investigations revealed elevated ESR and beta 2 microglobulin, monoclonal peak on
      serum protein electrophoresis, high IG with lambda restriction on serum, and
      urine immunofixation with increased lymphocytes and plasma cells in the bone
      marrow. A diagnosis of lymphoplasmacytic lymphoma complicated by blinding
      hyperviscosity retinopathy was made. In the absence of an aphaeresis machine, he
      received four cycles of manual exchange blood transfusion (EBT) and commenced
      with chlorambucil/prednisolone due to difficulty in obtaining blood for continued
      EBT. His general condition and VA has improved and he is stable for more than six
      months into treatment. 

PMID- 24883218
TI  - Simultaneous Gastric and Duodenal Erosions due to Adjustable Gastric Banding for
      Morbid Obesity.
AB  - Erosion is an uncommon but feared late complication of adjustable gastric banding
      for morbid obesity. A high index of clinical suspicion is required, since
      symptoms are usually vague and nonspecific. Diagnosis is confirmed on upper
      gastrointestinal endoscopy and band removal is the mainstay of treatment, with
      band revision or conversion to other bariatric modalities at a later stage.
      Duodenal erosion is a much rarer complication, caused by the connection tubing of
      the band. We present our experience with a case of simultaneous gastric and
      duodenal erosions, managed by laparoscopic explantation of the band, primary
      suture repair of the duodenum, and omentopexy. 

PMID- 24883219
TI  - Tracheoesophageal Fistula due to a Damaged Tracheal Stent.
AB  - We describe the management of a tracheoesophageal fistula due to a damaged
      tracheal stent, which was first inserted to treat tracheal stenosis. A 29-year
      old woman with a history of treated epilepsy had a seizure and suffered from
      smoke inhalation during a fire. Breathing difficulties appeared and gradually
      worsened; consultation was obtained two years afterward. After undergoing a
      thorough examination, the patient was diagnosed with tracheal strangulation. A
      noncovered, metallic stent was inserted. When the patient was 37 years old, she
      was admitted to our hospital for the treatment of a tracheoesophageal fistula. We
      diagnosed it as a tracheoesophageal fistula due to the collapse of the damaged
      tracheal stent toward the esophageal side, and we decided to perform a
      mediastinal tracheostomy. Granulation may be formed in the circumference of a
      stent that has been present for a prolonged period, and removal of the stent may
      become difficult. This case suggests that insertion of a noncovered, metallic
      stent is contraindicated for a benign disease. 

PMID- 24883213
TI  - The maternal brain: an organ with peripartal plasticity.
AB  - The time of pregnancy, birth, and lactation, is characterized by numerous
      specific alterations in several systems of the maternal body. Peripartum
      associated changes in physiology and behavior, as well as their underlying
      molecular mechanisms, have been the focus of research since decades, but are
      still far from being entirely understood. Also, there is growing evidence that
      pregnancy and lactation are associated with a variety of alterations in neural
      plasticity, including adult neurogenesis, functional and structural synaptic
      plasticity, and dendritic remodeling in different brain regions. All of the
      mentioned changes are not only believed to be a prerequisite for the proper fetal
      and neonatal development, but moreover to be crucial for the physiological and
      mental health of the mother. The underlying mechanisms apparently need to be
      under tight control, since in cases of dysregulation, a certain percentage of
      women develop disorders like preeclampsia or postpartum mood and anxiety
      disorders during the course of pregnancy and lactation. This review describes
      common peripartum adaptations in physiology and behavior. Moreover, it
      concentrates on different forms of peripartum-associated plasticity including
      changes in neurogenesis and their possible underlying molecular mechanisms.
      Finally, consequences of malfunction in those systems are discussed. 

PMID- 24883220
TI  - Epididymal polar dissociation: a previously undescribed anatomical variant.
AB  - The normal male external genitalia include the testicles with the epididymis
      attached posteriorly and the vas deferens arising from this. This case describes
      an anatomical variation of this normal anatomy not previously reported in the
      literature. A 17-year-old boy presented with symptoms of intermittent testicular
      torsion and underwent scrotal exploration. On the left side there was a bell
      clapper deformity with the epididymis separated into two parts with the lower
      pole high in the scrotum and attached to the tunica vaginalis. A normal vas
      deferens was seen to arise from the isolated lower pole of the epididymis. There
      was no connection between the vas deferens and the testis or upper pole of
      epidiymis. This case reminds us of the possibility of anatomical variations and
      the importance of keeping them in mind to prevent complications at time of
      surgery. 

PMID- 24883221
TI  - Renal paraganglioma: report of a case managed by robotic assisted laparoscopic
      partial nephrectomy and review of the literature.
AB  - We describe the pathological and clinical presentation of a rare case of renal
      paraganglioma occurring as an incidental left renal mass in a 58-year-old woman.
      The patient underwent robotic assisted laparoscopic partial nephrectomy, which is
      the first one in the literature. 

PMID- 24883223
TI  - A Pathway Idea for Model Building.
AB  - Models, mathematical or stochastic, which move from one functional form to
      another through pathway parameters, so that in between stages can be captured,
      are examined in this article. Models which move from generalized type-1 beta
      family to type-2 beta family, to generalized gamma family to generalized Mittag
      Leffler family to Levy distributions are examined here. It is known that one can
      likely find an approximate model for the data at hand whether the data are coming
      from biological, physical, engineering, social sciences or other areas. Different
      families of functions are connected through the pathway parameters and hence one
      will find a suitable member from within one of the families or in between stages
      of two families. Graphs are provided to show the movement of the different models
      showing thicker tails, thinner tails, right tail cut off etc.

PMID- 24883222
TI  - Metachronous bilateral granulocytic sarcoma of the testis in a young adult: a
      report of an unusual entity.
AB  - Granulocytic sarcomas are rare tumors composed of neoplastic blood cells,
      typically occurring during the course of acute nonlymphoblastic leukemia or
      before its onset. We present a case of a 23-year-old young adult man with
      metachronous granulocytic sarcoma of the testis without hematologic
      manifestations who was diagnosed with granulocytic sarcoma (GS). The patient was
      treated with right orchiectomy but relapsed with a left testicular mass 16 months
      later when a left orchiectomy was performed. The patient has been free of disease
      for 13 months following the left orchiectomy. This case highlights a rare
      hematologic cancer that urologists and pathologists should be aware of since it
      can present as a testicular mass. Only 3 cases of testicular GS without an
      associated hematologic disorder have been described. To the best of our
      knowledge, our patient is the first reported case in the English literature of
      metachronous GS of the testis with no evidence of hematologic disorder. 

PMID- 24883224
TI  - Quantitative Analysis of Panax ginseng by FT-NIR Spectroscopy.
AB  - Near-infrared spectroscopy (NIRS), a rapid and efficient tool, was used to
      determine the total amount of nine ginsenosides in Panax ginseng. In the study,
      the regression models were established using multivariate regression methods with
      the results from conventional chemical analytical methods as reference values.
      The multivariate regression methods, partial least squares regression (PLSR) and
      principal component regression (PCR), were discussed and the PLSR was more
      suitable. Multiplicative scatter correction (MSC), second derivative, and
      Savitzky-Golay smoothing were utilized together for the spectral preprocessing.
      When evaluating the final model, factors such as correlation coefficient (R (2))
      and the root mean square error of prediction (RMSEP) were considered. The final
      optimal results of PLSR model showed that root mean square error of prediction
      (RMSEP) and correlation coefficients (R (2)) in the calibration set were 0.159
      and 0.963, respectively. The results demonstrated that the NIRS as a new method
      can be applied to the quality control of Ginseng Radix et Rhizoma. 

PMID- 24883225
TI  - Clustering Scatter Plots Using Data Depth Measures.
AB  - Clustering is rapidly becoming a powerful data mining technique, and has been
      broadly applied to many domains such as bioinformatics and text mining. However,
      the existing methods can only deal with a data matrix of scalars. In this paper,
      we introduce a hierarchical clustering procedure that can handle a data matrix of
      scatter plots. To more accurately reflect the nature of data, we introduce a
      dissimilarity statistic based on "data depth" to measure the discrepancy between
      two bivariate distributions without oversimplifying the nature of the underlying
      pattern. We then combine hypothesis testing with hierarchical clustering to
      simultaneously cluster the rows and columns of the data matrix of scatter plots.
      We also propose novel painting metrics and construct heat maps to allow
      visualization of the clusters. We demonstrate the utility and power of our new
      clustering method through simulation studies and application to a microbe-host
      interaction study.

PMID- 24883228
TI  - Intelligent Systems and Technology for Integrative and Predictive Medicine: An
      ACP Approach.
AB  - One of the principal goals in medicine is to determine and implement the best
      treatment for patients through fastidious estimation of the effects and benefits
      of therapeutic procedures. The inherent complexities of physiological and
      pathological networks that span across orders of magnitude in time and length
      scales, however, represent fundamental hurdles in determining effective
      treatments for patients. Here we argue for a new approach, called ACP-based
      approach that combines artificial (societies), computational (experiments) and
      parallel (execution)methods in intelligent systems and technology for integrative
      and predictive medicine, or more general, precision medicine and smart health
      management. The advent of artificial societies that collect the clinically
      relevant information in prognostics and therapeutics provides a promising
      platform for organizing and experimenting complex physiological systems toward
      integrative medicine. The ability of computational experiments to analyze
      distinct, interactive systems such as the host mechanisms, pathological pathways,
      therapeutic strategies as well as other factors using the artificial systems will
      enable control and management through parallel execution of real and arficial
      systems concurrently within the integrative medicine context. The development of
      this framework in integrative medicine fueled by close collaborations between
      physicians, engineers, and scientists will result in preventive and predictive
      practices of personal, proactive, and precision nature, including rational
      combinatorial treatments, adaptive therapeutics, and patient-oriented disease
      management.

PMID- 24883227
TI  - LL-37 induced cystitis and the receptor for advanced glycation end-products
      (RAGE) pathway.
AB  - To elucidate pathways in bladder inflammation, we employed our physiologically
      relevant LL-37 induced cystitis model. Based on inflammatory studies involving
      other organ systems implicating the receptor for advanced glycation end-products
      (RAGE), we first hypothesized that RAGE is critically involved in LL-37 induced
      cystitis. We further hypothesized a common RAGE ligand - high mobility group box
      1 (HMGB1) is up-regulated in bladders challenged with LL-37. Finally, we
      hypothesized NF-kappaB dependent inflammatory genes are activated in LL-37
      induced cystitis. Testing our first hypothesis, C57Bl/6 mice were challenged with
      either saline (control) or 320 MUM of LL-37 intravesically for 1 hr. After 12 or
      24 hours, tissues were examined with immunohistochemistry (IHC) for RAGE, and
      both mRNA and protein isolation for respective qRT-PCR and Western Blot analysis.
      Our second hypothesis was tested by employing HMGB1 IHC. Testing our final
      hypothesis, qRT-PCR was performed investigating five genes: TNFalpha, IL-6, IL
      1beta, GM-CSF, COX-2. In control and LL-37 challenged tissues, IHC for RAGE
      revealed similar qualitative expression. Evaluation with qRT-PCR and Western Blot
      for RAGE revealed diminished expression at the mRNA and protein level within LL
      37 challenged bladders. IHC for HMGB1 revealed a moderate qualitative increase
      within LL-37 challenged tissues. Finally, with the exception of TNF alpha, all NF
      kappaB dependent inflammatory genes yielded substantial up-regulation. We have
      employed our LL-37 induced cystitis model to gain insight towards a possible
      mechanistic pathway involved in bladder inflammation. This work provides data for
      future studies involving the inflammatory ligand HMGB1, RAGE, and receptor
      pathways that activate NF-kappaB.

PMID- 24883226
TI  - Why has Nature Chosen Lutein and Zeaxanthin to Protect the Retina?
AB  - Age-related macular degeneration (AMD) is associated with a low level of macular
      carotenoids in the eye retina. Only two carotenoids, namely lutein and zeaxanthin
      are selectively accumulated in the human eye retina from blood plasma where more
      than twenty other carotenoids are available. The third carotenoid which is found
      in the human retina, meso-zeaxanthin is formed directly in the retina from
      lutein. All these carotenoids, named also macular xanthophylls, play key roles in
      eye health and retinal disease. Macular xanthophylls are thought to combat light
      induced damage mediated by reactive oxygen species by absorbing the most damaging
      incoming wavelength of light prior to the formation of reactive oxygen species (a
      function expected of carotenoids in nerve fibers) and by chemically and
      physically quenching reactive oxygen species once they are formed (a function
      expected of carotenoids in photoreceptor outer segments). There are two major
      hypotheses about the precise location of macular xanthophylls in the nerve fiber
      layer of photoreceptor axons and in photoreceptor outer segments. According to
      the first, macular xanthophylls transversely incorporate in the lipid-bilayer
      portion of membranes of the human retina. According to the second, macular
      xanthophylls are protein-bound by membrane-associated, xanthophyll-binding
      proteins. In this review we indicate specific properties of macular xanthophylls
      that could help explain their selective accumulation in the primate retina with
      special attention paid to xanthophyll-membrane interactions.

PMID- 24883230
TI  - A Multi-Locus Approach to Treating Fibromyalgia by Boosting Dopaminergic Activity
      in the Meso-Limbic System of the Brain.

PMID- 24883229
TI  - Adenoviral Vectors for Hemophilia Gene Therapy.
AB  - Hemophilia is an inherited blood clotting disorder resulting from deficiency of
      blood coagulation factors. Current standard of care for hemophilia patients is
      frequent intravenous infusions of the missing coagulation factor. Gene therapy
      for hemophilia involves the introduction of a normal copy of the deficient
      coagulation factor gene thereby potentially offering a definitive cure for the
      bleeding disorder. A variety of approaches have been pursued for hemophilia gene
      therapy and this review article focuses on those that use adenoviral vectors.

PMID- 24883231
TI  - Muscle Gene Therapy for Hemophilia.
AB  - Muscle-directed gene therapy for hemophilia is an attractive strategy for
      expression of therapeutic levels of clotting factor as evident from preclinical
      studies and an early phase clinical trial. Notably, local FIX expression by AAV
      mediated direct intramuscular injection to skeletal muscle persists for years.
      Development of intravascular delivery of AAV vector approaches to skeletal muscle
      resulted in vector in widespread areas of the limb and increased expression of
      FIX in hemophilia B dogs. The use of FIX variants with improved biological
      activity may provide the opportunity to increase the efficacy of these
      approaches. Studies for hemophilia A are less developed at this point, but
      utilizing transgenes that improve hemostasis independent of FIX and FVIII has
      potential therapeutic application for both hemophilia A and B. Continuous
      monitoring of humoral and T cell responses to the transgene and AAV capsid in
      human trials will be critical for the translation of these promising approaches
      for muscle gene therapy for hemophilia.

PMID- 24883232
TI  - Duplication of TBK1 Stimulates Autophagy in iPSC-derived Retinal Cells from a
      Patient with Normal Tension Glaucoma.
AB  - Duplication of theTBK1 gene causes normal tension glaucoma (NTG); however the
      mechanism by which this copy number variation leads to retinal ganglion cell
      death is poorly understood. The ability to use skin-derived induced pluripotent
      stem cells (iPSCs) to investigate the function or dysfunction of a mutant gene
      product in inaccessible tissues such as the retina now provides us with the
      ability to interrogate disease pathophysiology in vitro. iPSCs were generated
      from dermal fibroblasts obtained from a patient with TBK1-associated NTG, via
      viral transduction of the transcription factors OCT4, SOX2, KLF4, and c-MYC.
      Retinal progenitor cells and subsequent retinal ganglion cell-like neurons were
      derived using our previously developed stepwise differentiation protocol.
      Differentiation to retinal ganglion-like cells was demonstrated via rt-PCR
      targeted against TUJ1, MAP2, THY1, NF200, ATOH7 and BRN3B and
      immunohistochemistry targeted against NF200 and ATOH7. Western blot analysis
      demonstrated that both fibroblasts and retinal ganglion cell-like neurons derived
      from NTG patients with TBK1 gene duplication have increased levels of LC3-II
      protein (a key marker of autophagy). Duplication of TBK1 has been previously
      shown to increase expression of TBK1 and here we demonstrate that the same
      duplication leads to activation of LC3-II. This suggests that TBK1-associated
      glaucoma may be caused by dysregulation (over-activation) of this catabolic
      pathway.

PMID- 24883233
TI  - Dual responsiveness of a tunable thermo-sensitive polypeptide.
AB  - The temperature and pH dependent solubility of poly(gamma-propargyl L-glutamate)
      (PPLG) functionalized through copper catalyzed 1,3 cycloaddition reaction between
      an alkyne and azide can be tuned with precision over a broad range of conditions
      by varying the ratio of substitution of short oligo ethylene glycol and
      diisopropylamine side groups.

PMID- 24883235
TI  - The Big Picture: Evidence Base and Current Trials in Cardiac CT.
AB  - Cardiac computed tomography angiography (CCTA) has technically matured into a
      robust imaging modality for various cardiac disorders. Whereas early trials
      focused on assessment of the efficacy of CCTA in comparison with established
      recommended methods, current research efforts focus on the effectiveness of the
      technique in specific clinical scenarios. In this article, we provide an overview
      of recent technology advances, describe major clinical scenarios in which CCTA
      has been evaluated, and detail pertinent evidence from completed or ongoing
      clinical trials, including its use to investigate acute chest pain, its use among
      patients with stable chest pain syndrome, and its prognostic value for the
      occurrence of cardiovascular events.

PMID- 24883234
TI  - PET/CT in Oncology: Current Status and Perspectives.
AB  - The discovery of the Warburg effect in the early twentieth century followed by
      the development of the fluorinated glucose analogue 18F-fluorodeoxyglucose (18F
      FDG) and the invention of positron emission tomographs laid the foundation of
      clinical PET/CT. This review discusses the challenges and obstacles in clinical
      adoption of this technique. We then discuss advances in instrumentation,
      including the critically important introduction of PET/CT and current PET/CT
      protocols. Moreover, we provide evidence for the clinical utility of PET/CT for
      patient management and its potential impact on patient outcome, and address its
      cost and cost-effectiveness. Although this review largely focuses on 18F-FDG
      imaging, we also discuss a variety of additional molecular imaging approaches
      that can be used for cancer phenotyping with PET. Throughout this review we
      emphasize the critical contributions of CT to the strength of PET/CT.

PMID- 24883236
TI  - Therapy of Genetic Disorders-Novel Therapies for Duchenne Muscular Dystrophy.
AB  - Duchenne muscular dystrophy (DMD) is an inherited, progressive muscle wasting
      disorder caused by mutations in the dystrophin gene. An increasing variety of
      approaches are moving towards clinical testing that all aim to restore dystrophin
      production and to enhance or preserve muscle mass. Gene therapy methods are being
      developed to replace the defective dystrophin gene or induce dystrophin
      production from mutant genes. Stem cell approaches are being developed to replace
      lost muscle cells while also bringing in new dystrophin genes. This review
      summarizes recent progress in the field with an emphasis on clinical
      applications.

PMID- 24883237
TI  - Future Therapies for IgE-Mediated Food Allergy.
AB  - Food allergy is prevalent, affecting approximately 4-8% of children. There is no
      currently approved treatment for food allergy, and while strict allergen
      avoidance is recommended it is difficult to achieve and therefore accidental
      exposures and reactions are common. There is an urgent need for the development
      of therapeutic approaches that will improve the health and quality of life of
      children with food allergy. The majority of current clinical research focus is on
      specific food allergen immunotherapy through oral, sublingual, or epicutaneous
      routes. Pre-clinical research has focused on making improvements to the safety
      and efficacy of allergen immunotherapy through modifications of allergen
      structure and addition of immuno-modulatory factors. The number of novel
      therapeutics for food allergy reaching the level of clinical trials remains
      disappointingly low, and there is a need for an expansion of pre-clinical
      research to provide safe, practical and novel approaches to the treatment of food
      allergy.

PMID- 24883238
TI  - Genetics of Psychosis in Alzheimer Disease.
AB  - Psychosis occurs in approximately half of patients with Alzheimer disease (AD
      with psychosis, AD+P). AD+P patients have more rapid cognitive decline, greater
      behavioral symptoms, and higher mortality than do AD patients without psychosis.
      Studies in three independent cohorts have shown that psychosis in AD aggregates
      in families, with estimated heritability of 29.5 - 60.8%. These findings have
      motivated studies to investigate and uncover the genes responsible for the
      development of psychosis, with the ultimate goal of identifying potential
      biologic mechanisms that may serve as leads to specific therapies. Linkage
      analyses have implicated loci on chromosomes 2, 6, 7, 8, 15, and 21 with AD+P.
      Association studies of APOE do not support it as a risk gene for psychosis in AD.
      No other candidate genes, such as neurodegenerative and monoamine genes, show
      conclusive evidence of association with AD+P. However, a recent genome-side
      association study has produced some promising leads, including among them genes
      that have been associated with schizophrenia. This review summarizes the current
      knowledge of the genetic basis of AD+P.

PMID- 24883240
TI  - A taxonomic review of the Late Jurassic eucryptodiran turtles from the Jura
      Mountains (Switzerland and France).
AB  - Background. Eucryptodiran turtles from the Late Jurassic (mainly Kimmeridgian)
      deposits of the Jura Mountains (Switzerland and France) are among the earliest
      named species traditionally referred to the Plesiochelyidae, Thalassemydidae, and
      Eurysternidae. As such, they are a reference for the study of Late Jurassic
      eucryptodires at the European scale. Fifteen species and four genera have been
      typified based on material from the Late Jurassic of the Jura Mountains. In the
      past 50 years, diverging taxonomic reassessments have been proposed for these
      turtles with little agreement in sight. In addition, there has been a shift of
      focus from shell to cranial anatomy in the past forty years, although most of
      these species are only represented by shell material. As a result, the taxonomic
      status of many of these 15 species remains ambiguous, which prevents
      comprehensive comparison of Late Jurassic turtle assemblages throughout Europe
      and hinders description of new discoveries, such as the new assemblage recently
      unearthed in the vicinity of Porrentruy, Switzerland. Methods. An exhaustive
      reassessment of the available material provides new insights into the comparative
      anatomy of these turtles. The taxonomic status of each of the 15 species typified
      based on material from the Late Jurassic of the Jura Mountains is evaluated. New
      diagnoses and general descriptions are provided for each valid taxon. Results.
      Six out of the 15 available species names are recognized as valid: Plesiochelys
      etalloni, Craspedochelys picteti, Craspedochelys jaccardi, Tropidemys langii,
      Thalassemys hugii, and 'Thalassemys' moseri. The intraspecific variability of the
      shell of P. etalloni is discussed based on a sample of about 30 relatively
      complete specimens from Solothurn, Switzerland. New characters are proposed to
      differentiate P. etalloni, C. picteti, and C. jaccardi, therefore rejecting the
      previously proposed synonymy of these forms. Based partly on previously
      undescribed specimens, the plastral morphology of Th. hugii is redescribed. The
      presence of lateral plastral fontanelles is notably revealed in this species,
      which calls into question the traditional definitions of the Thalassemydidae and
      Eurysternidae. Based on these new data, Eurysternum ignoratum is considered a
      junior synonym of Th. hugii. The Eurysternidae are therefore only represented by
      Solnhofia parsonsi in the Late Jurassic of the Jura Mountains. Finally, 'Th.'
      moseri is recognized as a valid species, although a referral to the genus
      Thalassemys is refuted. 

PMID- 24883241
TI  - The impact of social context on learning and cognitive demands for interactive
      virtual human simulations.
AB  - Interactive virtual human (IVH) simulations offer a novel method for training
      skills involving person-to-person interactions. This article examines the
      effectiveness of an IVH simulation for teaching medical students to assess rare
      cranial nerve abnormalities in both individual and small-group learning contexts.
      Individual (n = 26) and small-group (n = 30) interaction with the IVH system was
      manipulated to examine the influence on learning, learner engagement, perceived
      cognitive demands of the learning task, and instructional efficiency. Results
      suggested the IVH activity was an equally effective and engaging instructional
      tool in both learning structures, despite learners in the group learning contexts
      having to share hands-on access to the simulation interface. Participants in both
      conditions demonstrated a significant increase in declarative knowledge post
      training. Operation of the IVH simulation technology imposed moderate cognitive
      demand but did not exceed the demands of the task content or appear to impede
      learning. 

PMID- 24883239
TI  - Framework Surgery for Treatment of Unilateral Vocal Fold Paralysis.
AB  - Laryngeal framework surgery is the current gold standard treatment for unilateral
      vocal fold paralysis. It provides a permanent solution to glottic insufficiency
      caused by injury to the recurrent laryngeal nerve. Various modifications to the
      original Isshiki type I laryngoplasty procedure have been described to improve
      voice and swallowing outcomes. The success of this procedure is highly dependent
      on the experience of the surgeon as it epitomizes the intersection of art and
      science in the field. The following article reviews the evidence, controversies,
      and complications related to laryngoplasty for unilateral vocal fold paralysis.
      It also provides a detailed analysis of how and when arytenoid-positioning
      procedures should be considered, and summarizes the literature on postoperative
      outcomes.

PMID- 24883242
TI  - Light enhanced calcification in Stylophora pistillata: effects of glucose,
      glycerol and oxygen.
AB  - Zooxanthellate corals have long been known to calcify faster in the light than in
      the dark, however the mechanism underlying this process has been uncertain. Here
      we tested the effects of oxygen under controlled pCO2 conditions and fixed carbon
      sources on calcification in zooxanthellate and bleached microcolonies of the
      branching coral Stylophora pistillata. In zooxanthellate microcolonies, oxygen
      increased dark calcification rates to levels comparable to those measured in the
      light. However in bleached microcolonies oxygen alone did not enhance
      calcification, but when combined with a fixed carbon source (glucose or
      glycerol), calcification increased. Respiration rates increased in response to
      oxygen with greater increases when oxygen is combined with fixed carbon. ATP
      content was largely unaffected by treatments, with the exception of glycerol
      which decreased ATP levels. 

PMID- 24883243
TI  - Coral-algae metabolism and diurnal changes in the CO2-carbonate system of bulk
      sea water.
AB  - Precise measurements were conducted in continuous flow seawater mesocosms located
      in full sunlight that compared metabolic response of coral, coral-macroalgae and
      macroalgae systems over a diurnal cycle. Irradiance controlled net photosynthesis
      (P net), which in turn drove net calcification (G net), and altered pH. P net
      exerted the dominant control on [CO3 (2-)] and aragonite saturation state
      (Omegaarag) over the diel cycle. Dark calcification rate decreased after sunset,
      reaching zero near midnight followed by an increasing rate that peaked at 03:00
      h. Changes in Omegaarag and pH lagged behind G net throughout the daily cycle by
      two or more hours. The flux rate P net was the primary driver of calcification.
      Daytime coral metabolism rapidly removes dissolved inorganic carbon (DIC) from
      the bulk seawater and photosynthesis provides the energy that drives G net while
      increasing the bulk water pH. These relationships result in a correlation between
      G net and Omegaarag, with Omegaarag as the dependent variable. High rates of H(+)
      efflux continued for several hours following mid-day peak G net suggesting that
      corals have difficulty in shedding waste protons as described by the Proton Flux
      Hypothesis. DIC flux (uptake) followed P net and G net and dropped off rapidly
      following peak P net and peak G net indicating that corals can cope more
      effectively with the problem of limited DIC supply compared to the problem of
      eliminating H(+). Over a 24 h period the plot of total alkalinity (AT ) versus
      DIC as well as the plot of G net versus Omegaarag revealed a circular hysteresis
      pattern over the diel cycle in the coral and coral-algae mesocosms, but not the
      macroalgae mesocosm. Presence of macroalgae did not change G net of the corals,
      but altered the relationship between Omegaarag and G net. Predictive models of
      how future global changes will effect coral growth that are based on oceanic
      Omegaarag must include the influence of future localized P net on G net and
      changes in rate of reef carbonate dissolution. The correlation between Omegaarag
      and G net over the diel cycle is simply the response of the CO2-carbonate system
      to increased pH as photosynthesis shifts the equilibria and increases the [CO3 (2
      )] relative to the other DIC components of [HCO3 (-)] and [CO2]. Therefore
      Omegaarag closely tracked pH as an effect of changes in P net, which also drove
      changes in G net. Measurements of DIC flux and H(+) flux are far more useful than
      concentrations in describing coral metabolism dynamics. Coral reefs are systems
      that exist in constant disequilibrium with the water column. 

PMID- 24883244
TI  - Effect of nutrition survey 'cleaning criteria' on estimates of malnutrition
      prevalence and disease burden: secondary data analysis.
AB  - Tackling childhood malnutrition is a global health priority. A key indicator is
      the estimated prevalence of malnutrition, measured by nutrition surveys. Most
      aspects of survey design are standardised, but data 'cleaning criteria' are not.
      These aim to exclude extreme values which may represent measurement or data-entry
      errors. The effect of different cleaning criteria on malnutrition prevalence
      estimates was unknown. We applied five commonly used data cleaning criteria (WHO
      2006; EPI-Info; WHO 1995 fixed; WHO 1995 flexible; SMART) to 21 national
      Demographic and Health Survey datasets. These included a total of 163,228
      children, aged 6-59 months. We focused on wasting (low weight-for-height), a key
      indicator for treatment programmes. Choice of cleaning criteria had a marked
      effect: SMART were least inclusive, resulting in the lowest reported malnutrition
      prevalence, while WHO 2006 were most inclusive, resulting in the highest. Across
      the 21 countries, the proportion of records excluded was 3 to 5 times greater
      when using SMART compared to WHO 2006 criteria, resulting in differences in the
      estimated prevalence of total wasting of between 0.5 and 3.8%, and differences in
      severe wasting of 0.4-3.9%. The magnitude of difference was associated with the
      standard deviation of the survey sample, a statistic that can reflect both
      population heterogeneity and data quality. Using these results to estimate case
      loads for treatment programmes resulted in large differences for all countries.
      Wasting prevalence and caseload estimations are strongly influenced by choice of
      cleaning criterion. Because key policy and programming decisions depend on these
      statistics, variations in analytical practice could lead to inconsistent and
      potentially inappropriate implementation of malnutrition treatment programmes. We
      therefore call for mandatory reporting of cleaning criteria use so that results
      can be compared and interpreted appropriately. International consensus is
      urgently needed regarding choice of criteria to improve the comparability of
      nutrition survey data. 

PMID- 24883245
TI  - On growth and form of irregular coiled-shell of a terrestrial snail: Plectostoma
      concinnum (Fulton, 1901) (Mollusca: Caenogastropoda: Diplommatinidae).
AB  - The molluscan shell can be viewed as a petrified representation of the organism's
      ontogeny and thus can be used as a record of changes in form during growth.
      However, little empirical data is available on the actual growth and form of
      shells, as these are hard to quantify and examine simultaneously. To address
      these issues, we studied the growth and form of a land snail that has an
      irregularly coiled and heavily ornamented shell-Plectostoma concinnum. The growth
      data were collected in a natural growth experiment and the actual form changes of
      the aperture during shell ontogeny were quantified. We used an ontogeny axis that
      allows data of growth and form to be analysed simultaneously. Then, we examined
      the association between the growth and the form during three different whorl
      growing phases, namely, the regular coiled spire phase, the transitional
      constriction phase, and the distortedly-coiled tuba phase. In addition, we also
      explored the association between growth rate and the switching between whorl
      growing mode and rib growing mode. As a result, we show how the changes in the
      aperture ontogeny profiles in terms of aperture shape, size and growth
      trajectory, and the changes in growth rates, are associated with the different
      shell forms at different parts of the shell ontogeny. These associations suggest
      plausible constraints that underlie the three different shell ontogeny phases and
      the two different growth modes. We found that the mechanism behind the
      irregularly coiled-shell is the rotational changes of the animal's body and
      mantle edge with respect to the previously secreted shell. Overall, we propose
      that future study should focus on the role of the mantle and the columellar
      muscular system in the determination of shell form. 

PMID- 24883246
TI  - Retrospective cohort study of anti-tumor necrosis factor agent use in a veteran
      population.
AB  - Introduction. Anti-tumor necrosis factor (TNF) agents are effective for several
      immunologic conditions (rheumatoid arthritis (RA), Crohn's disease (CD), and
      psoriasis). The purpose of this study was to evaluate the efficacy and safety of
      anti-TNF agents via chart review. Methods. Single-site, retrospective cohort
      study that evaluated the efficacy and safety of anti-TNF agents in veterans
      initiated between 2010 and 2011. Primary aim evaluated response at 12 months post
      index date. Secondary aims evaluated initial response prior to 12 months post
      index date and infection events. Results. A majority of patients were prescribed
      anti-TNF agents for CD (27%) and RA (24%). Patients were initiated on etanercept
      (41%), adalimumab (40%), and infliximab (18%) between 2010 and 2011. No
      differences in patient demographics were reported. Response rates were high
      overall. Sixty-five percent of etanercept patients, 82% of adalimumab patients,
      and 59% of infliximab patients were either partial or full responders,
      respectively. Approximately 16%, 11%, and 12% of etanercept, adalimumab, and
      infliximab were non-responders, respectively. Infections between the groups were
      non-significant. Etanercept and adalimumab patients had higher but non
      significant odds of being a responder relative to infliximab. Conclusions. Most
      patients initiated with anti-TNF agent were responders at 12 months follow-up for
      all indications in a veteran population. 

PMID- 24883248
TI  - Effects of terrigenous sediment on settlement and survival of the reef coral
      Pocillopora damicornis.
AB  - Survival and settlement of Pocillopora damicornis larvae on hard surfaces covered
      with fine (<63 um) terrigenous red clay was measured in laboratory Petri dishes.
      The dishes were prepared with sediment films of various thicknesses covering the
      bottoms. Coral larvae were incubated in the dishes for two weeks and the percent
      that settled on the bottom was determined. There was a statistically significant
      relationship between the amount of sediment and coral recruitment on the bottom,
      with no recruitment on surfaces having a sediment cover above 0.9 mg cm(-2).
      Experimental conditions for the delicate coral larvae were favorable in these
      experiments. Total survival over the two week settlement tests expressed as the
      sum of coral recruits and live larvae at the end of the experiment did not show a
      significant decline, so the major impact of the sediment was on successful
      settlement rather than on mortality. Larval substrate selection behavior was the
      primary factor in the observed result. 

PMID- 24883247
TI  - Quantifying cryptic Symbiodinium diversity within Orbicella faveolata and
      Orbicella franksi at the Flower Garden Banks, Gulf of Mexico.
AB  - The genetic composition of the resident Symbiodinium endosymbionts can strongly
      modulate the physiological performance of reef-building corals. Here, we used
      quantitative metabarcoding to investigate Symbiodinium genetic diversity in two
      species of mountainous star corals, Orbicella franksi and Orbicella faveolata,
      from two reefs separated by 19 km of deep water. We aimed to determine if the
      frequency of different symbiont genotypes varied with respect to coral host
      species or geographic location. Our results demonstrate that across the two reefs
      both coral species contained seven haplotypes of Symbiodinium, all identifiable
      as clade B and most closely related to type B1. Five of these haplotypes have not
      been previously described and may be endemic to the Flower Garden Banks. No
      significant differences in symbiont composition were detected between the two
      coral species. However, significant quantitative differences were detected
      between the east and west banks for three background haplotypes comprising 0.1%
      10% of the total. The quantitative metabarcoding approach described here can help
      to sensitively characterize cryptic genetic diversity of Symbiodinium and
      potentially contribute to the understanding of physiological variations among
      coral populations. 

PMID- 24883249
TI  - Organic carbon inventories in natural and restored Ecuadorian mangrove forests.
AB  - Mangroves can capture and store organic carbon and their protection and therefore
      their restoration is a component of climate change mitigation. However, there are
      few empirical measurements of long-term carbon storage in mangroves or of how
      storage varies across environmental gradients. The context dependency of this
      process combined with geographically limited field sampling has made it difficult
      to generalize regional and global rates of mangrove carbon sequestration. This
      has in turn hampered the inclusion of sequestration by mangroves in carbon cycle
      models and in carbon offset markets. The purpose of this study was to estimate
      the relative carbon capture and storage potential in natural and restored
      mangrove forests. We measured depth profiles of soil organic carbon content in 72
      cores collected from six sites (three natural, two restored, and one afforested)
      surrounding Muisne, Ecuador. Samples up to 1 m deep were analyzed for organic
      matter content using loss-on-ignition and values were converted to organic carbon
      content using an accepted ratio of 1.72 (g/g). Results suggest that average soil
      carbon storage is 0.055 +/- 0.002 g cm(-3) (11.3 +/- 0.8% carbon content by dry
      mass, mean +/- 1 SE) up to 1 m deep in natural sites, and 0.058 +/- 0.002 g cm(
      3) (8.0 +/- 0.3%) in restored sites. These estimates are concordant with
      published global averages. Evidence of equivalent carbon stocks in restored and
      afforested mangrove patches emphasizes the carbon sink potential for
      reestablished mangrove systems. We found no relationship between sediment carbon
      storage and aboveground biomass, forest structure, or within-patch location. Our
      results demonstrate the long-term carbon storage potential of natural mangroves,
      high effectiveness of mangrove restoration and afforestation, a lack of
      predictability in carbon storage strictly based on aboveground parameters, and
      the need to establish standardized protocol for quantifying mangrove sediment
      carbon stocks. 

PMID- 24883250
TI  - The role of a water bug, Sigara striata, in freshwater food webs.
AB  - Freshwater food webs are dominated by aquatic invertebrates whose trophic
      relationships are often poorly known. Here, I used laboratory experiments to
      study the role of a water bug, Sigara striata, as a potential predator and prey
      in food webs of stagnant waters. Multiple-choice predation experiment revealed
      that Sigara, which had been considered mostly herbivorous, also consumed larvae
      of Chironomus midges. Because they often occur in high densities and are among
      the most ubiquitous aquatic insects, Sigara water bugs may be important predators
      in fresh waters. A second experiment tested the role of Sigara as a potential
      prey for 13 common invertebrate predators. Mortality of Sigara inflicted by
      different predators varied widely, especially depending on body mass, foraging
      mode (ambush/searching) and feeding mode (chewing/suctorial) of the predators.
      Sigara was highly vulnerable to ambush predators, while searching predators
      caused on average 8.1 times lower mortality of Sigara. Additionally, suctorial
      predators consumed on average 6.6 times more Sigara individuals than chewing
      predators, which supports previous results hinting on potentially different
      predation pressures of these two types of predators on prey populations. The
      importance of these two foraging-related traits demonstrates the need to move
      from body mass based to multiple trait based descriptions of food web structure.
      Overall, the results suggests that detailed experimental studies of common but
      insufficiently known species can significantly enhance our understanding of food
      web structure. 

PMID- 24883251
TI  - Violent deaths of media workers associated with conflict in Iraq, 2003-2012.
AB  - Background. The violent deaths of media workers is a critical issue worldwide,
      especially in areas of political and social instability. Such deaths can be a
      particular concern as they may undermine the development and functioning of an
      open and democratic society. Method. Data on the violent deaths of media workers
      in Iraq for ten years (2003-2012) were systematically collated from five
      international databases. Analyses included time trends, weapons involved,
      nationality of the deceased, outcome for perpetrators and location of death.
      Results. During this ten-year period, there were 199 violent deaths of media
      workers in Iraq. The annual number increased substantially after the invasion in
      2003 (peaking at n = 47 in 2007) and then declined (n = 5 in 2012). The peak
      years (2006-2007) for these deaths matched the peak years for estimated violent
      deaths among civilians. Most of the media worker deaths (85%) were Iraqi
      nationals. Some were killed whilst on assignment in the field (39%) and 28%
      involved a preceding threat. Common perpetrators of the violence were: political
      groups (45%), and coalition forces (9%), but the source of the violence was often
      unknown (29%). None of the perpetrators have subsequently been prosecuted (as of
      April 2014). For each violent death of a media worker, an average of 3.1 other
      people were also killed in the same attack (range 0-100 other deaths).
      Discussion. This analysis highlights the high number of homicides of media
      workers in Iraq in this conflict period, in addition to the apparently total
      level of impunity. One of the potential solutions may be establishing a
      functioning legal system that apprehends offenders and puts them on trial. The
      relatively high quality of data on violent deaths in this occupational group,
      suggests that it could act as one sentinel population within a broader
      surveillance system of societal violence in conflict zones. 

PMID- 24883252
TI  - Mining transcriptomic data to study the origins and evolution of a plant
      allopolyploid complex.
AB  - Allopolyploidy combines two progenitor genomes in the same nucleus. It is a
      common speciation process, especially in plants. Deciphering the origins of
      polyploid species is a complex problem due to, among other things, extinct
      progenitors, multiple origins, gene flow between different polyploid populations,
      and loss of parental contributions through gene or chromosome loss. Among the
      perennial species of Glycine, the plant genus that includes the cultivated
      soybean (G. max), are eight allopolyploid species, three of which are studied
      here. Previous crossing studies and molecular systematic results from two nuclear
      gene sequences led to hypotheses of origin for these species from among extant
      diploid species. We use several phylogenetic and population genomics approaches
      to clarify the origins of the genomes of three of these allopolyploid species
      using single nucleotide polymorphism data and a guided transcriptome assembly.
      The results support the hypothesis that all three polyploid species are fixed
      hybrids combining the genomes of the two putative parents hypothesized on the
      basis of previous work. Based on mapping to the soybean reference genome, there
      appear to be no large regions for which one homoeologous contribution is missing.
      Phylogenetic analyses of 27 selected transcripts using a coalescent approach also
      are consistent with multiple origins for these allopolyploid species, and suggest
      that origins occurred within the last several hundred thousand years. 

PMID- 24883253
TI  - Synthetic surfactant containing SP-B and SP-C mimics is superior to single
      peptide formulations in rabbits with chemical acute lung injury.
AB  - Background. Chemical spills are on the rise and inhalation of toxic chemicals may
      induce chemical acute lung injury (ALI)/acute respiratory distress syndrome
      (ARDS). Although the pathophysiology of ALI/ARDS is well understood, the absence
      of specific antidotes has limited the effectiveness of therapeutic interventions.
      Objectives. Surfactant inactivation and formation of free radicals are important
      pathways in (chemical) ALI. We tested the potential of lipid mixtures with
      advanced surfactant protein B and C (SP-B and C) mimics to improve oxygenation
      and lung compliance in rabbits with lavage- and chemical-induced ALI/ARDS.
      Methods. Ventilated young adult rabbits underwent repeated saline lung lavages or
      underwent intratracheal instillation of hydrochloric acid to induce ALI/ARDS.
      After establishment of respiratory failure rabbits were treated with a single
      intratracheal dose of 100 mg/kg of synthetic surfactant composed of 3% Super Mini
      B (S-MB), a SP-B mimic, and/or SP-C33 UCLA, a SP-C mimic, in a lipid mixture
      (DPPC:POPC:POPG 5:3:2 by weight), the clinical surfactant Infasurf((r)), a bovine
      lung lavage extract with SP-B and C, or synthetic lipids alone. End-points
      consisted of arterial oxygenation, dynamic lung compliance, and protein and lipid
      content in bronchoalveolar lavage fluid. Potential mechanism of surfactant action
      for S-MB and SP-C33 UCLA were investigated with captive bubble surfactometry
      (CBS) assays. Results. All three surfactant peptide/lipid mixtures and Infasurf
      equally lowered the minimum surface tension on CBS, and also improved oxygenation
      and lung compliance. In both animal models, the two-peptide synthetic surfactant
      with S-MB and SP-C33 UCLA led to better arterial oxygenation and lung compliance
      than single peptide synthetic surfactants and Infasurf. Synthetic surfactants and
      Infasurf improved lung function further in lavage- than in chemical-induced
      respiratory failure, with the difference probably due to greater capillary
      alveolar protein leakage and surfactant dysfunction after HCl instillation than
      following lung lavage. At the end of the duration of the experiments, synthetic
      surfactants provided more clinical stability in ALI/ARDS than Infasurf, and the
      protein content of bronchoalveolar lavage fluid was lowest for the two-peptide
      synthetic surfactant with S-MB and SP-C33 UCLA. Conclusion. Advanced synthetic
      surfactant with robust SP-B and SP-C mimics is better equipped to tackle
      surfactant inactivation in chemical ALI than synthetic surfactant with only a
      single surfactant peptide or animal-derived surfactant. 

PMID- 24883254
TI  - Multi-gene analysis of Symbiodinium dinoflagellates: a perspective on rarity,
      symbiosis, and evolution.
AB  - Symbiodinium, a large group of dinoflagellates, live in symbiosis with marine
      protists, invertebrate metazoans, and free-living in the environment.
      Symbiodinium are functionally variable and play critical energetic roles in
      symbiosis. Our knowledge of Symbiodinium has been historically constrained by the
      limited number of molecular markers available to study evolution in the genus.
      Here we compare six functional genes, representing three cellular compartments,
      in the nine known Symbiodinium lineages. Despite striking similarities among the
      single gene phylogenies from distinct organelles, none were evolutionarily
      identical. A fully concatenated reconstruction, however, yielded a well-resolved
      topology identical to the current benchmark nr28S gene. Evolutionary rates
      differed among cellular compartments and clades, a pattern largely driven by
      higher rates of evolution in the chloroplast genes of Symbiodinium clades D2 and
      I. The rapid rates of evolution observed amongst these relatively uncommon
      Symbiodinium lineages in the functionally critical chloroplast may translate into
      potential innovation for the symbiosis. The multi-gene analysis highlights the
      potential power of assessing genome-wide evolutionary patterns using recent
      advances in sequencing technology and emphasizes the importance of integrating
      ecological data with more comprehensive sampling of free-living and symbiotic
      Symbiodinium in assessing the evolutionary adaptation of this enigmatic
      dinoflagellate. 

PMID- 24883255
TI  - Formation of 1-octen-3-ol from Aspergillus flavus conidia is accelerated after
      disruption of cells independently of Ppo oxygenases, and is not a main cause of
      inhibition of germination.
AB  - Eight-carbon (C8) volatiles, such as 1-octen-3-ol, are ubiquitous among fungi.
      They are the volatiles critical for aroma and flavor of fungi, and assumed to be
      signals controlling germination of several fungi. In this study, we found that
      intact Aspergillus flavus conidia scarcely synthesized C8 volatiles but repeated
      freeze-thaw treatment that made the cell membrane permeable promoted (R)-1-octen
      3-ol formation. Loss or down regulation of any one of five fatty acid oxygenases
      (PpoA, PpoB, PpoC, PpoD or lipoxygenase) hypothesized contribute to 1-octen-3-ol
      formation had little impact on production of this volatile. This suggested that
      none of the oxygenases were directly involved in the formation of 1-octen-3-ol or
      that compensatory pathways exist in the fungus. Germination of the conidia was
      markedly inhibited at high density (1.0 * 10(9)spores mL(-1)). It has been
      postulated that 1-octen-3-ol is an autoinhibitor suppressing conidia germination
      at high density. 1-Octen-3-ol at concentration of no less than 10 mM was needed
      to suppress the germination while the concentration of 1-octen-3-ol in the
      suspension at 1.0 * 10(9) mL(-1) was under the detection limit (<1 uM). Thus, 1
      octen-3-ol was not the principal component responsible for inhibition of
      germination. Instead, it was evident that the other heat-labile factor(s)
      suppressed conidial germination. 

PMID- 24883256
TI  - Brain transcriptome sequencing and assembly of three songbird model systems for
      the study of social behavior.
AB  - Emberizid sparrows (emberizidae) have played a prominent role in the study of
      avian vocal communication and social behavior. We present here brain
      transcriptomes for three emberizid model systems, song sparrow Melospiza melodia,
      white-throated sparrow Zonotrichia albicollis, and Gambel's white-crowned sparrow
      Zonotrichia leucophrys gambelii. Each of the assemblies covered fully or in part,
      over 89% of the previously annotated protein coding genes in the zebra finch
      Taeniopygia guttata, with 16,846, 15,805, and 16,646 unique BLAST hits in song,
      white-throated and white-crowned sparrows, respectively. As in previous studies,
      we find tissue of origin (auditory forebrain versus hypothalamus and whole brain)
      as an important determinant of overall expression profile. We also demonstrate
      the successful isolation of RNA and RNA-sequencing from post-mortem samples from
      building strikes and suggest that such an approach could be useful when
      traditional sampling opportunities are limited. These transcriptomes will be an
      important resource for the study of social behavior in birds and for data driven
      annotation of forthcoming whole genome sequences for these and other bird
      species. 

PMID- 24883257
TI  - Spatial and temporal distribution of the invasive lionfish Pterois volitans in
      coral reefs of Tayrona National Natural Park, Colombian Caribbean.
AB  - The lionfish Pterois volitans is an invasive species throughout the Western
      Atlantic that disturbs functioning of local ecosystems such as coral reefs via
      fast and intense consumption of small fish and invertebrates. In 2009, lionfish
      populated the bays of Tayrona National Natural Park (TNNP), a biodiversity
      hotspot in the Colombian Caribbean that is strongly influenced by changing
      environmental conditions due to a rainy and dry season. So far, the spatial and
      temporal distribution of P. volitans in the bays of TNNP is unknown. Therefore,
      this study assessed the abundance and body lengths of P. volitans during monthly
      surveys throughout the year 2012 in four bays (thereof two bays where lionfish
      removals were undertaken) of TNNP at 10 m water depth in coral reefs using
      transect tools. Findings revealed lionfish abundances of 2.9 +/- 0.9 individuals
      ha(-1) with lengths of 20-25 cm for TNNP, hinting to an established, mostly adult
      local population. Actual TNNP lionfish abundances are thereby very similar to
      those at Indo-Pacific reef locations where the invasive lionfish formerly
      originated from. Significant spatial differences for lionfish abundances and body
      lengths between different bays in TNNP suggest habitat preferences of P. volitans
      depending on age. Lionfish abundances were highly variable over time, but without
      significant differences between seasons. Removals could not reduce lionfish
      abundances significantly during the period of study. This study therefore
      recommends improved management actions in order to control the already
      established invasive lionfish population in TNNP. 

PMID- 24883258
TI  - Growth and metal bioconcentration by conspecific freshwater macroalgae cultured
      in industrial waste water.
AB  - The bioremediation of industrial waste water by macroalgae is a sustainable and
      renewable approach to the treatment of waste water produced by multiple
      industries. However, few studies have tested the bioremediation of complex multi
      element waste streams from coal-fired power stations by live algae. This study
      compares the ability of three species of green freshwater macroalgae from the
      genus Oedogonium, isolated from different geographic regions, to grow in waste
      water for the bioremediation of metals. The experiments used Ash Dam water from
      Tarong power station in Queensland, which is contaminated by multiple metals (Al,
      Cd, Ni and Zn) and metalloids (As and Se) in excess of Australian water quality
      guidelines. All species had consistent growth rates in Ash Dam water, despite
      significant differences in their growth rates in "clean" water. A species
      isolated from the Ash Dam water itself was not better suited to the
      bioremediation of that waste water. While there were differences in the temporal
      pattern of the bioconcentration of metals by the three species, over the course
      of the experiment, all three species bioconcentrated the same elements
      preferentially and to a similar extent. All species bioconcentrated metals (Cu,
      Mn, Ni, Cd and Zn) more rapidly than metalloids (As, Mo and Se). Therefore,
      bioremediation in situ will be most rapid and complete for metals. Overall, all
      three species of freshwater macroalgae had the ability to grow in waste water and
      bioconcentrate elements, with a consistent affinity for the key metals that are
      regulated by Australian and international water quality guidelines. Together,
      these characteristics make Oedogonium a clear target for scaled bioremediation
      programs across a range of geographic regions. 

PMID- 24883259
TI  - Carbapenem-resistant enterobacteriaceae: analyzing knowledge and practice in
      healthcare providers.
AB  - Background. Gram negative antibiotic resistance is increasing worldwide as both
      carbapenem-resistant enterobacteriaceae (CREs) and Enterobacteriaceae producing
      extended spectrum beta-lactamases (ESBLs) become more common. Objective. We
      analyzed clinicians' knowledge regarding resistant gram-negative organisms with
      respect to infection control practices, prescribing practices and assessment of
      their patients' risk for resistant infections. Design. Online survey.
      Participants. Target population included clinicians who prescribe antibiotics
      i.e., medical doctors and mid-level practitioners, at three Massachusetts
      hospitals. Methods. Questionnaires were sent to 3 Tufts-affiliated teaching
      hospitals to assess level of knowledge and elucidate perceptions about gram
      negative resistance. Results. We received 434 responses from 3332 non-infectious
      disease clinicians (13%) surveyed at the three hospitals. 51.1% of clinicians
      correctly scored 50% or greater on the knowledge questions. Internal medicine
      clinicians had higher knowledge scores than non-internal medicine clinicians (62%
      vs 45%; OR = 1.67, p = 0.02). Clinicians within three years of training had
      higher scores than those with more than 10 years of training (64.3% vs 44%; OR =
      2.3, p = 0.002). Clinicians with fewer years since training and those with higher
      knowledge scores were more likely to appropriately consider certain patients at
      risk for resistant infections (p < 0.05). 54.4% of clinicians were very concerned
      about gram-negative antibiotic resistance. 64.6% of clinicians felt comfortable
      de-escalating antibiotics as cultures are available. Conclusion. We found overall
      low knowledge scores and much variability in the way clinicians assess whether
      certain patient populations are at risk for antibiotic resistance. Internal
      medicine clinicians and those with fewer years since completion of their training
      scored higher and more appropriately considered patients at risk for resistance.
      The majority of clinicians are concerned about gram-negative resistance and
      indicated they would de-escalate antibiotic therapy if they had susceptibility
      information. These results will help focus and target our teaching and awareness
      raising strategies. 

PMID- 24883260
TI  - Dominance hierarchies, diversity and species richness of vascular plants in an
      alpine meadow: contrasting short and medium term responses to simulated global
      change.
AB  - We studied the impact of simulated global change on a high alpine meadow plant
      community. Specifically, we examined whether short-term (5 years) responses are
      good predictors for medium-term (7 years) changes in the system by applying a
      factorial warming and nutrient manipulation to 20 plots in Latnjajaure, subarctic
      Sweden. Seven years of experimental warming and nutrient enhancement caused
      dramatic shifts in dominance hierarchies in response to the nutrient and the
      combined warming and nutrient enhancement treatments. Dominance hierarchies in
      the meadow moved from a community being dominated by cushion plants, deciduous,
      and evergreen shrubs to a community being dominated by grasses, sedges, and
      forbs. Short-term responses were shown to be inconsistent in their ability to
      predict medium-term responses for most functional groups, however, grasses showed
      a consistent and very substantial increase in response to nutrient addition over
      the seven years. The non-linear responses over time point out the importance of
      longer-term studies with repeated measurements to be able to better predict
      future changes. Forecasted changes to temperature and nutrient availability have
      implications for trophic interactions, and may ultimately influence the access to
      and palatability of the forage for grazers. Depending on what anthropogenic
      change will be most pronounced in the future (increase in nutrient deposits,
      warming, or a combination of them both), different shifts in community dominance
      hierarchies may occur. Generally, this study supports the productivity-diversity
      relationship found across arctic habitats, with community diversity peaking in
      mid-productivity systems and degrading as nutrient availability increases
      further. This is likely due the increasing competition in plant-plant
      interactions and the shifting dominance structure with grasses taking over the
      experimental plots, suggesting that global change could have high costs to
      biodiversity in the Arctic. 

PMID- 24883261
TI  - Salivary biomarkers for detection of oral squamous cell carcinoma - current state
      and recent advances.
AB  - Oral squamous cell carcinoma (OSCC) is the most common malignant neoplasm of the
      oral cavity. Detection of OSCC is currently based on thorough clinical oral
      examination combined with biopsy for histological analysis. Most cases of OSCC
      are not detected until the cancer has developed into advanced stages; thus, a
      reliable early stage diagnostic marker is needed. This literature review presents
      an overview of the status of current advances in salivary diagnostics for OSCC.
      Though many protein and mRNA salivary biomarkers have been identified that can
      detect OSCC with high sensitivity and specificity, the most discernable findings
      occur with the use of multiple markers. Studies that incorporate proteomic,
      transcriptomic, and potentially additional "omics", including methylomics, need
      to be initiated to bring technology to clinical applications and allow the best
      use of saliva in diagnosing OSCC.

PMID- 24883262
TI  - Immunopathogenesis Versus Protection in Dengue Virus Infections.
AB  - Dengue viruses (DENV) are mosquito-borne viruses that cause significant
      morbidity. The existence of four serotypes of DENV with partial immunologic cross
      reactivity creates the opportunity for individuals to experience multiple acute
      DENV infections over the course of their lifetimes. Research over the past
      several years has revealed complex interactions between DENV and the human innate
      and adaptive immune systems that can have either beneficial or detrimental
      influences on the outcome of infection. Further studies that seek to distinguish
      protective from pathological immune responses in the context of natural DENV
      infection as well as clinical trials of candidate DENV vaccines have an important
      place in efforts to control the global impact of this re-emerging viral disease.

PMID- 24883263
TI  - The Role of Maternal Breast Milk in Preventing Infantile Diarrhea in the
      Developing World.
AB  - Multiple interventions have been designed to decrease mortality and disability in
      children. Among these, breastfeeding is the most cost effective intervention for
      protecting children against diarrhea and all causes of mortality. Human milk is
      uniquely suited to the human infant, both in its nutritional composition and in
      the nonnutritive bioactive factors that promote survival and healthy development.
      Suboptimal breastfeeding has been linked with numerous adverse child health
      outcomes including increased incidence of diarrhea and pneumonia. This review
      provides an update regarding recent studies on the effect of breastfeeding on
      diarrhea morbidity and mortality in children in developing countries, describes
      major human milk components responsible for this protective effect
      (oligosaccharides, secretory immunoglobulins, lactoferrin, bacterial microbiota,
      etc.), and highlights areas for future research in this topic. Breastfeeding
      promotion remains an intervention of enormous public health potential to decrease
      global mortality and promote better growth and neurodevelopment in children.

PMID- 24883264
TI  - Early Life Origins of Metabolic Syndrome: The Role of Environmental Toxicants.
AB  - Metabolic syndrome (MetS) affects more than 47 million people in the U.S. Even
      more alarming, MetS, once regarded as an "adult problem", has become increasingly
      common in children. To date, most related research and intervention efforts have
      occurred in the adult medicine arena, with limited understanding of the root
      causes and lengthy latency of MetS. This review highlights new science on the
      early life origins of MetS, with a particular focus on exposure to two groups of
      environmental toxicants: endocrine disrupting chemicals (EDCs) and metals during
      the prenatal and early postnatal periods, and their specific effects and
      important differences in the development of MetS. It also summarizes available
      data on epigenetic effects, including the role of EDCs in the androgen/estrogen
      pathways. Emerging evidence supports the link between exposures to environmental
      toxicants during early life and the development of MetS later in life. Additional
      research is needed to address important research gaps in this area, including
      prospective birth cohort studies to delineate temporal and dose-response
      relationships, important differences in the effects of various environmental
      toxicants and their joint effects on MetS, as well as epigenetic mechanisms
      underlying the effects of specific toxicants such as EDCs and metals.

PMID- 24883267
TI  - Are journal articles accessed more times also cited more?

PMID- 24883265
TI  - Hypoxia alters MicroRNA expression in rat cortical pericytes.
AB  - Microvascular adaptation to metabolic stress is important in the maintenance of
      tissue homeostasis. Nowhere is this more important than in the central nervous
      system (CNS) where the cellular constituents of the neurovascularture including
      endothelial cells, pericytes and some astroglia must make fine-tuned
      autoregulatory modulations that maintain the delicate balance between oxygen
      availability and metabolic demand. miRNAs have been reported to play an important
      regulatory role in many cellular functions including cell differentiation, growth
      and proliferation, lineage determination, and metabolism. In this study, we
      investigated the possible role of miRNAs in the CNS capillary pericyte response
      to hypoxic stress. Micro-array analysis was used to examine the expression of 388
      rat miRNAs in primary rat cortical pericytes with and without exposure to low
      oxygen (1%) after 24 or 48 hr. Pericytes subjected to hypoxia showed 27 miRNAs
      that were higher than control and 31 that were lower. Validation and
      quantification was performed by Real Time RT-PCR on pericytes subjected to 2 hr,
      24 hr, or 48 hr of hypoxia. Hypoxia induced changes included physiological
      pathways governing the stress response, angiogenesis, migration and cell cycle
      regulation. miRNAs associated with HIF-1alpha (miR-322[1], miR-199a [2]), TGF
      beta1 (miR-140[3], miR-145[4], miR-376b-3p[5]) and VEGF (miR-126a[6], miR-297[7],
      miR-16[8], miR-17-5p[9]) were differentially regulated. Systematic and
      integrative analysis of possible gene targets analyzed by DAVID bioinformatics
      resource (http://david.abcc.ncifcrf.gov) and MetaSearch 2.0 (GeneGo) for some of
      these miRNAs was conducted to determine possible gene targets and pathways that
      may be affected by the post-transcriptional changes after hypoxic insult. 

PMID- 24883266
TI  - The influence of Cox-2 and bioactive lipids on hematological cancers.
AB  - Inflammation is implicated in the progression of multiple types of cancers
      including lung, colorectal, breast and hematological malignancies.
      Cyclooxygenases (Cox) -1 and -2 are important enzymes involved in the regulation
      of inflammation. Elevated Cox-2 expression is associated with a poor cancer
      prognosis. Hematological malignancies, which are among the top 10 most
      predominant cancers in the USA, express high levels of Cox-2. Current therapeutic
      approaches against hematological malignances are insufficient as many patients
      develop resistance or relapse. Therefore, targeting Cox-2 holds promise as a
      therapeutic approach to treat hematological malignancies. NSAIDs and Cox-2
      selective inhibitors are anti-inflammatory drugs that decrease prostaglandin and
      thromboxane production while promoting the synthesis of specialized proresolving
      mediators. Here, we review the evidence regarding the applicability of NSAIDs,
      such as aspirin, as well as Cox-2 specific inhibitors, to treat hematological
      malignancies. Furthermore, we discuss how FDA-approved Cox inhibitors can be used
      as anti-cancer drugs alone or in combination with existing chemotherapeutic
      treatments.

PMID- 24883268
TI  - The rat model in microsurgery education: classical exercises and new horizons.
AB  - Microsurgery is a precise surgical skill that requires an extensive training
      period and the supervision of expert instructors. The classical training schemes
      in microsurgery have started with multiday experimental courses on the rat model.
      These courses have offered a low threat supervised high fidelity laboratory
      setting in which students can steadily and rapidly progress. This simulated
      environment allows students to make and recognise mistakes in microsurgery
      techniques and thus shifts any related risks of the early training period from
      the operating room to the lab. To achieve a high level of skill acquisition
      before beginning clinical practice, students are trained on a comprehensive set
      of exercises the rat model can uniquely provide, with progressive complexity as
      competency improves. This paper presents the utility of the classical rat model
      in three of the earliest microsurgery training centres and the new prospects that
      this versatile and expansive training model offers. 

PMID- 24883269
TI  - Stepwise training for reconstructive microsurgery: the journey to becoming a
      confident microsurgeon in singapore.
AB  - Microsurgery training in Singapore began in 1980 with the opening of the
      Experimental Surgical Unit. Since then, the unit has continued to grow and have
      held microsurgical training courses biannually. The road to becoming a full
      fledged reconstructive surgeon requires the mastering of both microvascular as
      well as flap raising techniques and requires time, patience and good training
      facilities. In Singapore, over the past 2 decades, we have had the opportunity to
      develop good training facilities and to refine our surgical education programmes
      in reconstructive microsurgery. In this article, we share our experience with
      training in reconstructive microsurgery. 

PMID- 24883270
TI  - Development of a five-day basic microsurgery simulation training course: a cost
      analysis.
AB  - The widespread use of microsurgery in numerous surgical fields has increased the
      need for basic microsurgical training outside of the operating room. The
      traditional start of microsurgical training has been in undertaking a 5-day basic
      microsurgery course. In an era characterised by financial constraints in academic
      and healthcare institutions as well as increasing emphasis on patient safety,
      there has been a shift in microsurgery training to simulation environments. This
      paper reviews the stepwise framework of microsurgical skill acquisition providing
      a cost analysis of basic microsurgery courses in order to aid planning and
      dissemination of microsurgical training worldwide. 

PMID- 24883271
TI  - Research priorities in light of current trends in microsurgical training:
      revalidation, simulation, cross-training, and standardisation.
AB  - Plastic surgery training worldwide has seen a thorough restructuring over the
      past decade, with the introduction of formal training curricula and work-based
      assessment tools. Part of this process has been the introduction of revalidation
      and a greater use of simulation in training delivery. Simulation is an
      increasingly important tool for educators because it provides a way to reduce
      risks to both trainees and patients, whilst facilitating improved technical
      proficiency. Current microsurgery training interventions are often predicated on
      theories of skill acquisition and development that follow a 'practice makes
      perfect' model. Given the changing landscape of surgical training and advances in
      educational theories related to skill development, research is needed to assess
      the potential benefits of alternative models, particularly cross-training, a
      model now widely used in non-medical areas with significant benefits.
      Furthermore, with the proliferation of microsurgery training interventions and
      therefore diversity in length, cost, content and models used, appropriate
      standardisation will be an important factor to ensure that courses deliver
      consistent and effective training that achieves appropriate levels of competency.
      Key research requirements should be gathered and used in directing further
      research in these areas to achieve on-going improvement of microsurgery training.

PMID- 24883272
TI  - Robotic microsurgery optimization.
AB  - The increased application of the da Vinci robotic platform (Intuitive Surgical
      Inc.) for microsurgery has led to the development of new adjunctive surgical
      instrumentation. In microsurgery, the robotic platform can provide high
      definition 12*-15* digital magnification, broader range of motion, fine
      instrument handling with decreased tremor, reduced surgeon fatigue, and improved
      surgical productivity. This paper presents novel adjunctive tools that provide
      enhanced optical magnification, micro-Doppler sensing of vessels down to a 1-mm
      size, vein mapping capabilities, hydro-dissection, micro-ablation technology
      (with minimal thermal spread-CO2 laser technology), and confocal microscopy to
      provide imaging at a cellular level. Microsurgical outcomes from the use of these
      tools in the management of patients with infertility and chronic groin and
      testicular pain are reviewed. All these instruments have been adapted for the
      robotic console and enhance the robot-assisted microsurgery experience. As the
      popularity of robot-assisted microsurgery grows, so will its breadth of
      instrumentation. 

PMID- 24883273
TI  - Nanotechnology biomimetic cartilage regenerative scaffolds.
AB  - Cartilage has a limited regenerative capacity. Faced with the clinical challenge
      of reconstruction of cartilage defects, the field of cartilage engineering has
      evolved. This article reviews current concepts and strategies in cartilage
      engineering with an emphasis on the application of nanotechnology in the
      production of biomimetic cartilage regenerative scaffolds. The structural
      architecture and composition of the cartilage extracellular matrix and the
      evolution of tissue engineering concepts and scaffold technology over the last
      two decades are outlined. Current advances in biomimetic techniques to produce
      nanoscaled fibrous scaffolds, together with innovative methods to improve
      scaffold biofunctionality with bioactive cues are highlighted. To date, the
      majority of research into cartilage regeneration has been focused on articular
      cartilage due to the high prevalence of large joint osteoarthritis in an
      increasingly aging population. Nevertheless, the principles and advances are
      applicable to cartilage engineering for plastic and reconstructive surgery. 

PMID- 24883274
TI  - Effects of the diabetic condition on grafted fat survival: an experimental study
      using streptozotocin-induced diabetic rats.
AB  - BACKGROUND: Autologous fat grafts have been widely used for cosmetic purposes and
      for soft tissue contour reconstruction. Because diabetes mellitus is one of the
      major chronic diseases in nearly every country, the requirement for fat grafts in
      diabetes patients is expected to increase continuously. However, the circulation
      complications of diabetes are serious and have been shown to involve
      microvascular problems, impairing ischemia-driven neovascularization in
      particular. After injection, revascularization is vital to the survival of the
      grafted fat. In this study, the authors attempted to determine whether the
      diabetic condition inhibits the survival of injected fat due to impaired
      neovascularization. METHODS: The rat scalp was used for testing fat graft
      survival. Forty-four seven-week-old male Sprague-Dawley rats were allocated to a
      diabetic group or a control group. 1.0 mL of processed fat was injected
      subcutaneously into the scalp of each rat. The effect of diabetes was evaluated
      by calculating the volume and the weight of the grafted fat and by histologically
      analyzing the fat sections. RESULTS: The surviving fat graft volume and weight
      were considerably smaller in the diabetic group than in the control group
      (P<0.05), and histological evaluations showed less vascularity, and more cysts,
      vacuoles, and fibrosis in the diabetic group (P<0.05). Cellular integrity and
      inflammation were not considerably different in the two groups. CONCLUSIONS: As
      the final outcome, we found that the presence of diabetes might impair the
      survival and the quality of fat grafts, as evidenced by lower fat graft weights
      and volumes and poor histologic graft quality.

PMID- 24883275
TI  - Overexpression of KAI1 Protein in Diabetic Skin Tissues.
AB  - BACKGROUND: Patients with diabetes mellitus often have a difficult life,
      suffering from foot ulceration or amputation. Diabetes is characterized by
      chronic inflammation, and one of the features of inflammation is hypoxia.
      Recently, it has been reported that KAI1 is a hypoxia target gene. There is no
      published research on hypoxia-related KAI1 protein levels in human diabetic skin.
      Therefore, we have investigated the expression of KAI1 protein in diabetic skin
      tissue in vivo. METHODS: The expression of KAI1 protein was evaluated by western
      blotting in 6 diabetic skin tissue samples and 6 normal skin samples.
      Immunohistochemical staining was carried out to identify KAI1 expression.
      RESULTS: The western blotting revealed significantly increased expression of the
      KAI1 protein in diabetic skin tissues as compared to normal skin tissues.
      Immunohistochemical examination demonstrated that KAI1 was expressed in all
      diabetic skin tissues with moderate-to-strong positivity and weakly expressed in
      normal skin tissues. CONCLUSIONS: Our data suggest that a high expression of the
      KAI1 protein can be observed in diabetic skin tissue. To the best of our
      knowledge, this is the first report suggesting that KAI1 protein expression in
      diabetic skin tissues may be associated with chronic inflammatory states and
      hypoxia.

PMID- 24883276
TI  - Risk factors for complications after reconstructive surgery for sternal wound
      infection.
AB  - BACKGROUND: Although the utility of flaps for the treatment of sternal wound
      infections following median sternotomy has been reported for 30 years, there have
      been few reports on the risk factors for complications after reconstruction. The
      objective of this investigation was to identify factors related to complications
      after the reconstruction of sternal wound infections. METHODS: A retrospective
      analysis of 74 patients with reconstructive surgery after sternal wound infection
      over a 5-year period was performed. Clinical data including age, sex, body mass
      index (BMI), comorbidities, bacterial culture, previous cardiac surgery, wound
      depth, mortality rate, type of reconstructive procedure, and complication rate
      were collected. RESULTS: The patients' BMI ranged from 15.2 to 33.6 kg/m(2)
      (mean, 23.1+/-3.74 kg/m(2)). Wound closure complications after reconstructive
      surgery were observed in 36.5% of the cases. The mortality rate was 2.7%.
      Diabetes mellitus significantly affected the rate of wound closure complications
      (P=0.041). A significant difference in the number of complications was seen
      between Staphylococcus aureus (S. aureus) and coagulase-negative Staphylococci
      (P=0.011). There was a correlation between harvesting of the internal thoracic
      artery and postoperative complications (P=0.048). The complication rates of the
      pectoralis major flap, rectus abdominis flap, omentum flap, a combination of
      pectoralis major flap and rectus abdominis flap, and direct closure were 23.3%,
      33.3%, 100%, 37.5%, and 35.7%, respectively. CONCLUSIONS: Diabetes mellitus, S.
      aureus, harvesting of the internal thoracic artery, and omentum flap were
      significant factors for complications after reconstruction. The omentum flap
      volume may be related to the complications associated with the omentum flap
      transfer in the present study.

PMID- 24883277
TI  - Methylene blue dye-induced skin necrosis in immediate breast reconstruction:
      evaluation and management.
AB  - BACKGROUND: For early breast cancer patients, skin-sparing mastectomy or nipple
      sparing mastectomy with sentinel lymph node biopsy has become the mainstream
      treatment for immediate breast reconstruction in possible cases. However, a few
      cases of skin necrosis caused by methylene blue dye (MBD) used for sentinel lymph
      node localization have been reported. METHODS: Immediate breast reconstruction
      using a silicone implant was performed on 35 breasts of 34 patients after
      mastectomy. For sentinel lymph node localization, 1% MBD (3 mL) was injected into
      the subareolar area. The operation site was inspected in the postoperative
      evaluation. RESULTS: Six cases of immediate breast reconstruction using implants
      were complicated by methylene blue dye. One case of local infection was improved
      by conservative treatment. In two cases, partial necrosis and wound dehiscence of
      the incision areas were observed; thus, debridement and closure were performed.
      Of the three cases of wide skin necrosis, two cases underwent removal of the dead
      tissue and implants, followed by primary closure. In the other case, the breast
      implant was salvaged using latissimus dorsi musculocutaneous flap reconstruction.
      CONCLUSIONS: The complications were caused by MBD toxicity, which aggravated
      blood disturbance and skin tension after implant insertion. When planning
      immediate breast reconstruction using silicone implants, complications of MBD
      should be discussed in detail prior to surgery, and appropriate management in the
      event of complications is required.

PMID- 24883278
TI  - Delayed versus Delayed-Immediate Autologous Breast Reconstruction: A Blinded
      Evaluation of Aesthetic Outcomes.
AB  - BACKGROUND: The technique of delayed-immediate breast reconstruction includes
      immediate insertion of a tissue expander, post-mastectomy radiation, followed by
      reconstruction. The aesthetic benefits of delayed-immediate reconstruction
      compared to delayed reconstruction are postulated but remain unproven. The
      purpose of this study was to compare aesthetic outcomes in patients following
      delayed and delayed-immediate autologous breast reconstruction. METHODS: A
      retrospective analysis was performed of all patients who underwent delayed or
      delayed-immediate autologous breast reconstruction by the senior author from 2005
      to 2011. Postoperative photographs were used to evaluate aesthetic outcomes: skin
      quality, scar formation, superior pole contour, inferior pole contour, and
      overall aesthetic outcome. Ten non-biased reviewers assessed outcomes using a 5
      point Likert scale. Fisher's Exact and Wilcoxon-Mann-Whitney tests were used for
      comparative analysis. RESULTS: Patient age and body mass index were similar
      between delayed (n=20) and delayed-immediate (n=20) cohorts (P>0.05). Skin and
      scar quality was rated significantly higher in the delayed-immediate cohort (3.74
      vs. 3.05, P<0.001 and 3.41 vs. 2.79, P<0.001; respectively). Assessment of
      contour-related parameters, superior pole and inferior pole, found significantly
      improved outcomes in the delayed-immediate cohort (3.67 vs. 2.96, P<0.001 and
      3.84 vs. 3.06, P<0.001; respectively). Delayed-immediate breast reconstruction
      had a significantly higher overall score compared to delayed breast
      reconstructions (3.84 vs. 2.94, P<0.001). Smoking and the time interval from
      radiation to reconstruction were found to affect aesthetic outcomes (P<0.05).
      CONCLUSIONS: Preservation of native mastectomy skin may allow for improved
      skin/scar quality, breast contour, and overall aesthetic outcomes following a
      delayed-immediate reconstructive algorithm as compared to delayed breast
      reconstruction.

PMID- 24883279
TI  - Upper arm contouring with brachioplasty after massive weight loss.
AB  - BACKGROUND: As the obese population increases in Korea, the number of patients
      who are trying to lose weight has been increasing steadily. In these patients,
      skin laxity and deformation of the body contour occurs, which could possibly be
      corrected by various body contouring surgeries. Here, we introduce the
      brachioplasty method and our experience of various body contouring surgeries
      performed in our center. METHODS: From November 2009 to August 2011, five cases
      of brachioplasty were performed. When the patient presented with sagging of the
      lateral inframammary crease and bat wing deformity in the axilla, extended
      brachioplasty was performed; in this case, the deformation of the axilla and
      lateral chest was corrected at the same time. A traditional brachioplasty was
      performed when contouring was needed only for skin laxity in the upper arm.
      RESULTS: Complications, such as hematomas or nerve injuries, were not evident.
      Some patients experienced partial wound dehiscence due to tension or hypertrophic
      scars found during the follow-up. In general, all of the patients were satisfied
      with the improvement in their upper arm contour. CONCLUSIONS: Given the demands
      for body contouring surgery, the number of brachioplasty surgical procedures is
      expected to increase significantly, with abdominoplasty comprising a large
      portion of these surgeries. For the brachioplasty procedure, preparation and
      preoperative consultation regarding design of the surgery by experienced surgeons
      was important to prevent complications such as nerve damage or hematoma
      formation.

PMID- 24883280
TI  - Predicting the Permanent Safe Donor Area for Hair Transplantation in Koreans with
      Male Pattern Baldness according to the Position of the Parietal Whorl.
AB  - BACKGROUND: The most crucial factor in hair transplantation for male pattern
      baldness (MPB) patients is the efficient utilization of the donor-recipient
      ratio. However, there is no known factor that scientifically predicts the rate of
      progression of alopecia or indicates a permanently safe donor area. METHODS: The
      study considered 1,008 Korean adult males with MPB; of these, it excluded 56
      males with an absence of parietal whorls (PWs). The authors investigated the
      distance from the vertical bimeatal line (VM) to the PW, from the PW to the upper
      border of the helical rim (HR), and the distance from the PW to the occipital
      fringe (OF) in 952 subjects with a PW. Furthermore, we examined the distance from
      the PW to the OF considering the duration of alopecia and age in 322 subjects
      with vertex alopecia. RESULTS: The distance between the VM and PW varied from 1.5
      to 11 cm, with an average distance of 6.25 cm. The PW-HR distance ranged from 3.4
      to 17.5 cm, and the average distance was 7.79 cm. The PW-OF distance ranged from
      0.5 to 5.5 cm, and the average distance was 2.37 cm. CONCLUSIONS: For the PW,
      very large variations existed in the vertical direction. The position of the PW
      could predict the progression range of the total alopecia of the vertex. Alopecia
      mostly progresses within 6 cm of the PW toward the occipital side.

PMID- 24883281
TI  - Functional reconstruction of a combined tendocutaneous defect of the achilles
      using a segmental rectus femoris myofascial construct: a viable alternative.
AB  - The composite anterolateral thigh flap with vascularized fascia lata has emerged
      as a workhorse at our institution for complex Achilles defects requiring both
      tendon and soft tissue reconstruction. Safe elevation of this flap, however, is
      occasionally challenged by absent or inadequate perforators supplying the
      anterolateral thigh. When discovered intraoperatively, alternative options
      derived from the same vascular network can be pursued. We present the case of a
      74-year-old male who underwent composite Achilles defect reconstruction using a
      segmental rectus femoris myofascial free flap. Following graduated
      rehabilitation, postoperatively, the patient resumed full activity and was able
      to ambulate on his tip-toes. At 1-year follow-up, active total range of motion of
      the reconstructed ankle exceeded 85% of the unaffected side, and donor site
      morbidity was negligible. American Orthopaedic Foot and Ankle Society and Short
      Form-36 scores improved by 78.8% and 28.8%, respectively, compared to
      preoperative baseline assessments. Based on our findings, we advocate for use of
      the combined rectus femoris myofascial free flap as a rescue option for
      reconstructing composite Achilles tendon/posterior leg defects in the setting of
      inadequate anterolateral thigh perforators. To our knowledge, this is the first
      report to describe use of this flap for such an indication. 

PMID- 24883282
TI  - A rare form of congenital amniotic band syndrome: total circular abdominal
      constriction band.

PMID- 24883283
TI  - Moll's Cyst Occurring in the Orbital Septum.

PMID- 24883284
TI  - Incidental total necrosis of a successful flap due to a secondary operation after
      one year.

PMID- 24883285
TI  - Surgical removal of intraneural perineurioma arising in the brachial plexus using
      an interfascicular dissection technique.

PMID- 24883286
TI  - Diagnosis and management of ecthyma gangrenosum in chronic renal failure patient.

PMID- 24883287
TI  - Chondromyxoid fibroma of the finger.

PMID- 24883289
TI  - Intra-operative complications increase with successive number of cesarean
      sections: Myth or fact?
AB  - OBJECTIVE: To determine whether complications related to surgery increase with
      increasing number of cesarean sections (CSs) in upper segment placenta. To
      compare the complications in urgent and elective high order (4-6) repeat CSs.
      METHODS: A retrospective analysis of 519 women who underwent repeat CS was
      performed from January to December 2012. Women were divided into 3 groups: group
      1 with previous 3 CS (n=325), group 2 with previous 4 CS (n=139), and group 3
      with previous >=5 CS (n=55). RESULTS: Statistically significant differences (P <
      0.001) were observed among 3 groups, regarding mean gravidity, type of CS,
      midline incision and bilateral tubal ligation performed. The risks of severe
      intra-peritoneal adhesions, thin out lower uterine segment and bladder injury
      were significantly increased (P < 0.001) with increasing number of CS deliveries.
      Only one cesarean hysterectomy was done in group 1 due to post partum hemorrhage.
      No significant differences were found in blood loss, duration of surgery, post
      operative hospital stay as well as birth weight and Apgar scores of newborns. The
      elective and emergency CS groups of high order repeat CS had no remarkable
      differences in operative, post operative complications and fetal outcome.
      CONCLUSION: Women with repeat CS are at increased risk of having multiple intra
      operative surgical complications which increase with each subsequent CS. Pregnant
      women must be informed of the related risks which may affect counselling
      regarding possible tubal ligation.Women with repeat CS are at increased risk of
      having multiple intra-operative surgical complications which increase with each
      subsequent CS. Pregnant women must be informed of the related risks which may
      affect counselling regarding possible tubal ligation.

PMID- 24883288
TI  - Clinical characteristics and outcomes of antenatal fetal intra-abdominal
      umbilical vein varix detection.
AB  - OBJECTIVE: This study reviewed clinical characteristics of fetal intra-abdominal
      umbilical vein (FIUV) varices that were detected during antenatal ultrasound
      examinations. METHODS: Between January 2006 and January 2012, 121 cases of FIUV
      varices were detected and 7 cases were lost to follow-up. We retrospectively
      reviewed the medical records of 114 patients and neonates. RESULTS: From a total
      96,553 ultrasound examinations in 43,995 pregnancies, 121 cases of FIUV varices
      were identified (2.8 per 1,000 pregnancies). Gestational age at diagnosis was
      32.0 +/- 2.9 weeks (range, 20.1-36.3 weeks), the mean diameter of the FIUV varix
      was 12.6 +/- 2.1 mm (range, 8.0-21.0 mm) at initial diagnosis and the mean
      maximal diameter was 13.1 +/- 2.3 mm (range, 8.0-21.0 mm) during follow-up. The
      most severe pregnancy complications included one case of intrauterine fetal death
      and another case of fetal hydrops. Associated fetal anomalies (n = 11, 9.6%)
      detected by ultrasonography included bilateral renal pelvis dilatation,
      ventriculomegaly, cryptorchidism, incomplete renal duplication and pulmonary
      sequestration. A total of 104 cases (91.2%) were delivered at term and 10 cases
      (8.8%) were preterm deliveries before 37 weeks of gestation. CONCLUSION: FIUV
      varices that are not associated with fetal anomalies based on ultrasound
      examination during prenatal care have favorable pregnancy outcomes. Nevertheless,
      close fetal monitoring is recommended to decrease perinatal complications.

PMID- 24883290
TI  - Prenatal diagnosis of atrial isomerism in the Korean population.
AB  - OBJECTIVE: To report our experiences in the prenatal diagnosis of atrial
      isomerism and postnatal outcomes. METHODS: A total of 80 fetuses prenatally
      diagnosed with atrial isomerism were retrospectively analyzed between 1999 and
      2011 at a single institution. RESULTS: Of 43 fetuses with prenatally diagnosed
      right atrial isomerism (RAI), 40 cases were analyzed. The diagnostic accuracy was
      93%. The main intracardiac anomalies in RAI were atrioventricular septal defect
      (AVSD), abnormal pulmonary venous connection, bilateral superior vena cava
      (BSVC), and pulmonary atresia. Among 28 live births, three infants were lost to
      follow up, and the overall survival rate was 60%. Of 37 fetuses with prenatally
      diagnosed left atrial isomerism (LAI), 35 were evaluated. The diagnostic accuracy
      was 97%. The main intracardiac anomalies in LAI were ventricular septal defect,
      BSVC, AVSD, double outlet right ventricle, and bradyarrhythmia. Among seven
      patients with bradyarrhythmia, only one showed a complete atrioventricular block.
      All fetuses had an interrupted inferior vena cava with azygous continuation. The
      overall survival rate was 90%. CONCLUSION: Our study confirms the previous
      findings of fetal atrial isomerism. We also demonstrates a much lower prevalence
      of AVSD and complete heart block in LAI and a better survival rate in RAI.
      Although the postnatal outcomes for RAI were worse than those for LAI, successful
      postnatal surgery with active management improved the survival rate.

PMID- 24883291
TI  - S100 expression in dendritic cells is inversely correlated with tumor grade in
      endometrial carcinoma.
AB  - OBJECTIVE: The aim of this study was to determine the expression of S100 positive
      dendritic cells (DCs) and the relationship with clinicopathologic factors in
      endometrial carcinoma. METHODS: Samples were collected from 89 patients with
      endometrial endometrioid adenocarcinoma treated in Pusan National University
      Hospital from 2004 to 2011. Normal endometrial tissues were obtained from 30
      hysterectomized women with benign adnexal masses and served as controls. Paraffin
      embedded sections were immunohistochemically stained for S100 was performed, and
      the number of positive DCs was counted. The relationship of these cells to the
      stage, histological grade, myometrial invasion, and lymph node metastasis was
      analyzed. RESULTS: The proportion of S100-positive DCs in the endometrial
      endometrioid adenocarcinoma was 31.5% (28/89), which was significantly higher
      (P<0.05) than in the control group. The proportion of S100-positive DC expression
      was negatively correlated with the histologic grade, but was not associated with
      the stage, myometrial invasion, or lymph node metastasis. CONCLUSION: High DC
      density was inversely correlated with histologic grade in endometrial carcinoma.
      Tumor-infiltrating S100+ DCs may be used as pathologic marker in endometrial
      carcinoma.

PMID- 24883293
TI  - The effect of aromatase inhibitor letrozole incorporated in gonadotrophin
      releasing hormone antagonist multiple dose protocol in poor responders undergoing
      in vitro fertilization.
AB  - OBJECTIVE: To evaluate whether letrozole incorporated in a gonadotrophin
      releasing hormone (GnRH) antagonist multiple dose protocol (MDP) improved
      controlled ovarian stimulation (COS) and in vitro fertilization (IVF) results in
      poor responders who underwent IVF treatment. METHODS: In this retrospective
      cohort study, a total of 103 consecutive IVF cycles that were performed during
      either the letrozole/GnRH antagonist MDP cycles (letrozole group, n=46) or the
      standard GnRH antagonist MDP cycles (control group, n=57) were included in 103
      poor responders. COS results and IVF outcomes were compared between the two
      groups. RESULTS: Total dose and days of recombinant human follicle stimulating
      hormone (rhFSH) administered were significantly fewer in the letrozole group than
      in the control group. Duration of GnRH antagonist administered was also shorter
      in the letrozole group. The number of oocytes retrieved was significantly higher
      in the letrozole group. However, clinical pregnancy rate per cycle initiated,
      clinical pregnancy rate per embryo transfer, embryo implantation rate and
      miscarriage rate were similar in the two groups. CONCLUSION: The letrozole
      incorporated in GnRH antagonist MDP may be more effective because it results
      comparable pregnancy outcomes with shorter duration and smaller dose of rhFSH,
      when compared with the standard GnRH antagonist MDP.

PMID- 24883292
TI  - Elevated natural killer cell levels and autoimmunity synergistically decrease
      uterine blood flow during early pregnancy.
AB  - OBJECTIVE: To investigate whether natural killer (NK) cell and autoimmune
      antibody acts synergistically, by the action of autoantibodies to increase NK
      cell number and cytotoxicity, to decrease uterine blood flow during early
      pregnancy in pregnant women with a history of recurrent spontaneous abortion
      (RSA). METHODS: Seventy-five pregnant women (between 5 and 7 weeks gestation)
      with a history of unexplained RSA were included in the study group. Forty-one
      pregnant women without a history of RSA were included as controls. All women with
      a history of RSA were tested for autoantibodies and number of peripheral blood
      natural killer (pbNK) cell by flow cytometry. Study populations were stratified
      into four groups by existence of autoantibody and degree of increase of pbNK
      cells. The uterine radial artery resistance index (RI) was measured by color
      pulsed Doppler transvaginal ultrasound. RESULTS: The mean RI of the autoimmune
      antibody-positive (AA+) group (0.63+/-0.09) was significantly higher than that of
      the normal control group (0.53+/-0.10, P=0.001). The mean RI of the AA+/only-NK
      elevated (eNK) group (0.63+/-0.09) was significantly higher than those of the
      only-AA+ group (0.55+/-0.07, P=0.019) and the only-eNK group (0.57+/-0.07,
      P=0.021). CONCLUSION: Concurrent elevation in NK cells and autoimmunity results
      in decreased uterine blood flow during early pregnancy. However, the majority of
      cases of RSA remain unexplained and larger scale studies are needed to confirm
      our conclusion and to develop diagnostic and therapeutic plans for women with a
      history of RSA.

PMID- 24883294
TI  - A meningomyelocele with normal intracranial signs on ultrasound and false
      negative amniotic fluid alpha-fetoprotein and acetylcholinesterase.
AB  - Neural tube defects are the major targets of prenatal diagnoses, along with Down
      syndrome. Prenatal diagnosis of spina bifida is possible at second trimester of
      gestation through alpha-fetoprotein and acetylcholinesterase biochemistry assays
      and ultrasound. In particular, the discovery of characteristic intracranial signs
      on ultrasound leads to a very high diagnosis rate. However, it is rare for spina
      bifida to present without intracranial signs while also showing normal values of
      maternal serum alpha-fetoprotein, amniotic fluid alpha-fetoprotein, and
      acetylcholinesterase. In our hospital, a fetus with spina bifida was delivered at
      37+5 weeks' gestation by cesarean section, and was continually followed up over 2
      years to date. 

PMID- 24883295
TI  - Incidentally detected ganglioneuroma during pregnancy: A case report.
AB  - Retroperitoneal ganglioneuroma is a rare benign tumor, which is included in the
      neuroblastomas group. It can occur anywhere along the peripheral autonomic
      ganglion sites, and the tumor is often incidentally detected in asymptomatic
      patients or may produce symptoms related to the slow growing tumor. Surgical
      excision is the treatment of choice and the prognosis is good. We report a case
      of retroperitoneal ganglioneuroma, which was incidentally detected in the first
      trimester of pregnancy in a 29-year-old woman. Surgical resection of the
      ganglioneuroma was done at the time of cesarean section at full term without
      complications. 

PMID- 24883296
TI  - Laparoscopic transabdominal cervical cerclage: Case report of a woman without
      exocervix at 11 weeks gestation.
AB  - Cervical incompetence is characterized by painless dilatation of the incompetent
      cervix and results in miscarriages and preterm delivery during second trimester.
      We report a 25-year-old patient, gravid 2, para 1, at 11 weeks' gestation with
      the diagnosis of cervical incompetence, in whom transvaginal cerclage was not
      technically possible and laparoscopic cervical cerclage was performed
      successfully. There were no operative or immediate postoperative complications. A
      healthy infant was delivered at 35 weeks by cesarean section. Laparoscopic
      cervical cerclage during pregnancy can be safe and effective treatment for well
      selected patients with cervical incompetence and eliminates the need for open
      laparotomy. 

PMID- 24883297
TI  - A case of huge retroperitoneal liposarcoma in pregnancy.
AB  - A 39-year-old woman was referred to our hospital at 28+2 week gestation. Routine
      obstetric examination revealed a palpable pelvic mass. Initial investigation by
      magnetic resonance imaging demonstrated a huge solid mass with heterogeneous
      enhancement that completely filled the right side of the abdomen. She underwent
      two surgeries: a programmed cesarean section by Department of Obstetrics and
      Gynecology team and a laparotomy performed by the General Surgery team. Final
      diagnosis was de-differentiated liposarcoma (French Federation Nationale des
      Centres de Lutte Contre le Cancer grade 2/3). She has been treated with radiation
      therapy focusing on high risk area of retroperitoneum followed by adjuvant
      chemotherapy (doxorubicin and ifosfamide). Below is the full case with literature
      review. 

PMID- 24883298
TI  - Metastatic malignant melanoma with peritoneal seeding in a young woman: A case
      report.
AB  - Malignant melanomas of the uterus, either primary or metastatic, are extremely
      rare. They can be mistaken as other tumors, such as uterine sarcomas during
      diagnosis. We describe here the first case of a metastatic melanoma of the uterus
      with peritoneal seeding in a young woman. It was first diagnosed as a uterine
      sarcoma from a frozen-section biopsy. 

PMID- 24883299
TI  - The first successful live birth following preimplantation genetic diagnosis using
      PCR for type 1 citrullinemia.
AB  - Type 1 citrullinemia (CTLN1) is an autosomal recessive inherited metabolic
      disorder caused by anargininosuccinicnate synthetase deficiency. The patient was
      a 38-year-old Korean woman who is a carrier for CTLN1 and her first baby was
      diagnosed with CTLN1. Preimplantation genetic diagnosis (PGD) for CTLN1 in day 3
      embryos using polymerase chain reaction was performed for live birth of healthy
      baby who is no affected with CTLN1. One unaffected blastocyst was transferred.
      This resulted in a clinical pregnancy and the live birth of healthy male twin.
      They were confirmed to be unaffected with CTNL1 by post natal diagnosis. This is
      the first case report of the use of PGD for CTNL1. 

PMID- 24883300
TI  - The effects of single-dose rectal midazolam application on postoperative
      recovery, sedation, and analgesia in children given caudal anesthesia plus
      bupivacaine.
AB  - BACKGROUND: This study aimed to compare the effects of rectal midazolam addition
      after applying bupivacaine and caudal anesthesia on postoperative analgesia time,
      the need for additional analgesics, postoperative recovery, and sedation and to
      find out its adverse effects in children having lower abdominal surgery. METHODS:
      40 children between 2 and 10 years of ASA I-II were randomized, and they received
      caudal anesthesia under general anesthesia. Patients underwent the application of
      caudal block in addition to saline and 1 mL/kg bupivacaine 0.25%. In the
      postoperative period, Group C (n = 20) was given 5 mL saline, and Group M (n =
      20) was given 0.30 mg/kg rectal midazolam diluted with 5 mL saline. Sedation
      scale and postoperative pain scale (CHIPPS) of the patients were evaluated. The
      patients were observed for their analgesic need, first analgesic time, and
      adverse effects for 24 hours. RESULTS: Demographic and hemodynamic data of the
      two groups did not differ. Postoperative sedation scores in both groups were
      significantly lower compared with the preoperative period. There was no
      significant difference between the groups in terms of sedation and sufficient
      analgesia. CONCLUSIONS: We conclude that caudal anesthesia provided sufficient
      analgesia in peroperative and postoperative periods, and rectal midazolam
      addition did not create any differences. This trial is registered with
      ClinicalTrials.gov NCT02127489.

PMID- 24883301
TI  - Phyllanthus wightianus Mull. Arg.: a potential source for natural antimicrobial
      agents.
AB  - Phyllanthus wightianus belongs to Euphorbiaceae family having ethnobotanical
      importance. The present study deals with validating the antimicrobial potential
      of solvent leaf extracts of P. wightianus. 11 human bacterial pathogens (Bacillus
      subtilis, Streptococcus pneumoniae, Staphylococcus epidermidis, Proteus vulgaris,
      Pseudomonas aeruginosa, Klebsiella pneumoniae, Salmonella typhimurium,
      Escherichia coli, Shigella flexneri, Proteus vulgaris, and Serratia marcescens)
      and 4 fungal pathogens (Candida albicans, Cryptococcus neoformans, Mucor
      racemosus, and Aspergillus niger) were also challenged with solvent leaf extracts
      usingagar well and disc diffusion methods. Further, identification of the active
      component present in the bioactive extract was done using GC-MS analysis. Results
      show that all extracts exhibited broad spectrum (6-29 mm) of antibacterial
      activity on most of the tested organisms. The results highlight the fact that the
      well in agar method was more effective than disc diffusion method. Significant
      antimicrobial activity was detected in methanol extract against S. pneumoniae (29
      mm) with MIC and MBC values of 15.62 MUg/mL. GC-MS analysis revealed that 29
      bioactive constituents were present in methanolic extract of P. wightianus, of
      which 9,12-octadecaenioic acid (peak area 22.82%; RT-23.97) and N-hexadecanoic
      acid (peak area 21.55% RT-21.796) are the major compounds. The findings of this
      study show that P. wightianus extracts may be used as an anti-infective agent in
      folklore medicine.

PMID- 24883302
TI  - Pathway-driven discovery of rare mutational impact on cancer.
AB  - Identifying driver mutation is important in understanding disease mechanism and
      future application of custom tailored therapeutic decision. Functional analysis
      of mutational impact usually focuses on the gene expression level of the mutated
      gene itself. However, complex regulatory network may cause differential gene
      expression among functional neighbors of the mutated gene. We suggest a new
      approach for discovering rare mutations that have real impact in the context of
      pathway; the philosophy of our method is iteratively combining rare mutations
      until no more mutations can be added under the condition that the combined
      mutational event can statistically discriminate pathway level mRNA expression
      between groups with and without mutational events. Breast cancer patients with
      somatic mutation and mRNA expression were analyzed by our approach. Our approach
      is shown to sensitively capture mutations that change pathway level mRNA
      expression, concurrently discovering important mutations previously reported in
      breast cancer such as TP53, PIK3CA, and RB1. In addition, out of 15,819 genes
      considered in breast cancer, our approach identified mutational events of 32
      genes showing pathway level mRNA expression differences. 

PMID- 24883303
TI  - Immunohistochemical analysis of IL-6, IL-8/CXCR2 axis,  Tyr p-STAT-3, and SOCS-3
      in lymph nodes from patients with chronic lymphocytic leukemia: correlation
      between microvascular characteristics and prognostic significance.
AB  - A number of studies have looked into the pathophysiological role of angiogenesis
      in CLL, but the results have often been inconsistent. We aimed to gain direct
      insight into the angiogenic process in lymph nodes involved by CLL, focusing on
      proangiogenic cytokines and microvessel morphometry. The tissue levels of VEGF,
      Th-2 cytokines IL-6 and IL-8, IL-8 receptor CXCR2, and tyrosine p-STAT-3/SOCS-3
      axis modulating cytokine expression were evaluated immunohistochemically in 62
      CLL/SLL cases. Microvascular characteristics were evaluated by image analysis.
      Results were analyzed with regard to clinicopathological characteristics.
      Proliferation centers (PCs) were less well vascularised compared to non-PC areas.
      IL-8 and CXCR2 expression was distinctly uncommon as opposed to IL-6, VEGF and
      SOCS-3, which were detected in the vast majority of cases. The latter two
      molecule expressions were more pronounced in the PCs in ~ 40% of the cases. p
      STAT-3 immunoreactivity was recorded in 66.67% of the cases with a predilection
      for PCs. Microvessel morphometry was unrelated to proangiogenic cytokines, p-STAT
      3, SOCS-3, or survival. Microvascular caliber and VEGF expression were higher in
      Binet stage A, whereas IL-6 expression was higher in stage C. VEGF and p-STAT-3
      exerted a favorable effect on progression, which remained significant in
      multivariate analysis, thereby constituting potential outcome predictors in CLL
      patients.

PMID- 24883304
TI  - Osteoconductive potential of barrier nanoSiO2 PLGA membranes functionalized by
      plasma enhanced chemical vapour deposition.
AB  - The possibility of tailoring membrane surfaces with osteoconductive potential, in
      particular in biodegradable devices, to create modified biomaterials that
      stimulate osteoblast response should make them more suitable for clinical use,
      hopefully enhancing bone regeneration. Bioactive inorganic materials, such as
      silica, have been suggested to improve the bioactivity of synthetic biopolymers.
      An in vitro study on HOB human osteoblasts was performed to assess
      biocompatibility and bioactivity of SiO2 functionalized poly(lactide-co
      glycolide) (PLGA) membranes, prior to clinical use. A 15 nm SiO2 layer was
      deposited by plasma enhanced chemical vapour deposition (PECVD), onto a
      resorbable PLGA membrane. Samples were characterized by X-ray photoelectron
      spectroscopy, atomic force microscopy, scanning electron microscopy, and infrared
      spectroscopy (FT-IR). HOB cells were seeded on sterilized test surfaces where
      cell morphology, spreading, actin cytoskeletal organization, and focal adhesion
      expression were assessed. As proved by the FT-IR analysis of samples, the
      deposition by PECVD of the SiO2 onto the PLGA membrane did not alter the
      composition and other characteristics of the organic membrane. A temporal and
      spatial reorganization of cytoskeleton and focal adhesions and morphological
      changes in response to SiO2 nanolayer were identified in our model. The novedous
      SiO2 deposition method is compatible with the standard sterilization protocols
      and reveals as a valuable tool to increase bioactivity of resorbable PLGA
      membranes.

PMID- 24883305
TI  - The role of Wnt signaling in the development of Alzheimer's disease: a potential
      therapeutic target?
AB  - Accumulating evidence supports a key role for Wnt signaling in the development of
      the central nervous system (CNS) during embryonic development and in the
      regulation of the structure and function of the adult brain. Alzheimer's disease
      (AD) is the most common form of senile dementia, which is characterized by beta 
      amyloid (A beta ) deposition in specific brain regions. However, the molecular
      mechanism underlying AD pathology remains elusive. Dysfunctional Wnt signaling is
      associated with several diseases such as epilepsy, cancer, metabolic disease, and
      AD. Increasing evidence suggests that downregulation of Wnt signaling, induced by
      A beta , is associated with disease progression of AD. More importantly,
      persistent activation of Wnt signaling through Wnt ligands, or inhibition of
      negative regulators of Wnt signaling, such as Dickkopf-1 (DKK-1) and glycogen
      synthase kinase-3 beta (GSK-3 beta ) that are hyperactive in the disease state,
      is able to protect against A beta toxicity and ameliorate cognitive performance
      in AD. Together, these data suggest that Wnt signaling might be a potential
      therapeutic target of AD. Here, we review recent studies related to the
      progression of AD where Wnt signaling might be relevant and participate in the
      development of the disease. Then, we focus on the potential relevance of
      manipulating the Wnt signaling pathway for the treatment of AD. 

PMID- 24883307
TI  - Highly effective renaturation of a streptokinase from Streptococcus pyogenes DT7
      as inclusion bodies overexpressed in Escherichia coli.
AB  - The streptokinase (SK) is emerging as an important thrombolytic therapy agent in
      the treatment of patients suffering from cardiovascular diseases. We reported
      highly effective renaturation of a SK from S. pyogeness DT7 overexpressed in E.
      coli, purification, and biochemical characterization. A gene coding for the SK
      was cloned from S. pyogeness DT7. Because accumulation of active SK is toxic to
      the host cells, we have expressed it in the form of inclusion bodies. The mature
      protein was overexpressed in E. coli BL21 DE3/pESK under the control of the
      strong promoter tac induced by IPTG with a level of 60% of the total cell
      proteins. The activity of the rSK, renatured in phosphate buffer supplemented
      with Triton X-100 and glycerol, was covered with up to 41 folds of its initial
      activity. The purified of protein was identified with MALDI-TOF mass spectrometry
      through four peptide fragments, which showed 100% identification to the
      corresponding peptides of the putative SK from GenBank. Due to overexpression and
      highly effective renaturation of large amounts of inclusion bodies, the
      recombinant E. coli BL21 DE3/pESK system could be potentially applied for large
      scale production of SK used in the therapy of acute myocardial infarction.

PMID- 24883306
TI  - Calorie restriction in mammals and simple model organisms.
AB  - Calorie restriction (CR), which usually refers to a 20-40% reduction in calorie
      intake, can effectively prolong lifespan preventing most age-associated diseases
      in several species. However, recent data from both human and nonhumans point to
      the ratio of macronutrients rather than the caloric intake as a major regulator
      of both lifespan and health-span. In addition, specific components of the diet
      have recently been identified as regulators of some age-associated intracellular
      signaling pathways in simple model systems. The comprehension of the mechanisms
      underpinning these findings is crucial since it may increase the beneficial
      effects of calorie restriction making it accessible to a broader population as
      well. 

PMID- 24883308
TI  - Follistatin, an activin antagonist, ameliorates renal interstitial fibrosis in a
      rat model of unilateral ureteral obstruction.
AB  - Activin, a member of the TGF-beta superfamily, regulates cell growth and
      differentiation in various cell types. Activin A acts as a negative regulator of
      renal development as well as tubular regeneration after renal injury. However, it
      remains unknown whether activin A is involved in renal fibrosis. To clarify this
      issue, we utilized a rat model of unilateral ureteral obstruction (UUO). The
      expression of activin A was significantly increased in the UUO kidneys compared
      to that in contralateral kidneys. Activin A was detected in glomerular mesangial
      cells and interstitial fibroblasts in normal kidneys. In UUO kidneys, activin A
      was abundantly expressed by interstitial alpha-SMA-positive myofibroblasts.
      Administration of recombinant follistatin, an activin antagonist, reduced the
      fibrotic area in the UUO kidneys. The number of proliferating cells in the
      interstitium, but not in the tubules, was significantly lower in the follistatin
      treated kidneys. Expression of alpha-SMA, deposition of type I collagen and
      fibronectin, and CD68-positive macrophage infiltration were significantly
      suppressed in the follistatin-treated kidneys. These data suggest that activin A
      produced by interstitial fibroblasts acts as a potent profibrotic factor during
      renal fibrosis. Blockade of activin A action may be a novel approach for the
      prevention of renal fibrosis progression. 

PMID- 24883309
TI  - Snapback primer mediated clamping PCR for detection of EGFR and KRAS mutations in
      NSCLC patients by high resolution melting analysis.
AB  - Assays for detecting somatic mutations are requested with higher sensitivity and
      more convenience. Here, we describe snapback primer mediated allele clamping
      enrichment polymerase chain reaction (SPACE-PCR), a novel form of PCR that
      amplifies minority alleles selectively from mixtures. We replaced regular PCR
      with SPACE-PCR before sequencing or genotyping assays to improve mutation
      detection sensitivity by up to 100-fold in detecting EGFR and KRAS somatic
      mutations. Combined SPACE-PCR with analysis of snapback primer by high resolution
      melting (SPACE-HRM), the high sensitive system that enables a closed-tube
      detection of mutations after isolating mutants has been established, as low as
      1/10(5)-1/1000 mutant samples can be diagnosed. And finally, in a double-blind
      experiment of 150 cases of non-small-cell lung cancer (NSCLC) patients, compared
      with direct DNA sequencing and ADX-EGFR/KRAS mutation detection kit, up to 25% of
      the PCR-direct sequencing negative cases turned out to be positive in SPACE-HRM
      mutation tests; the specificity is 100%. Results demonstrated that the SPACE-HRM
      system we set up is a high sensitive assay that can be used for EGFR and KRAS
      allele enrichment and reliable detection. We anticipate that the method will be
      employed in multiple applications in the clinic, including diagnosis, scanner
      recurrence monitoring, and treatment management. 

PMID- 24883310
TI  - Through diffusion tensor magnetic resonance imaging to evaluate the original
      properties of neural pathways of patients with partial seizures and secondary
      generalization by individual anatomic reference atlas.
AB  - To investigate white matter (WM) abnormalities in neocortical epilepsy, we
      extract supratentorial WM parameters from raw tensor magnetic resonance images
      (MRI) with automated region-of-interest (ROI) registrations. Sixteen patients
      having neocortical seizures with secondarily generalised convulsions and 16 age
      matched normal subjects were imaged with high-resolution and diffusion tensor
      MRIs. Automated demarcation of supratentorial fibers was accomplished with
      personalized fiber-labeled atlases. From the individual atlases, we observed
      significant elevation of mean diffusivity (MD) in fornix (cres)/stria terminalis
      (FX/ST) and sagittal stratum (SS) and a significant difference in fractional
      anisotropy (FA) among FX/ST, SS, posterior limb of the internal capsule (PLIC),
      and posterior thalamic radiation (PTR). For patients with early-onset epilepsy,
      the diffusivities of the SS and the retrolenticular part of the internal capsule
      were significantly elevated, and the anisotropies of the FX/ST and SS were
      significantly decreased. In the drug-resistant subgroup, the MDs of SS and PTR
      and the FAs of SS and PLIC were significantly different. Onset age was positively
      correlated with increases in FAs of the genu of the corpus callosum. Patients
      with neocortical seizures and secondary generalisation had microstructural
      anomalies in WM. The changes in WM are relevant to early onset, progression, and
      severity of epilepsy. 

PMID- 24883311
TI  - Identification of a 20-gene expression-based risk score as a predictor of
      clinical outcome in chronic lymphocytic leukemia patients.
AB  - Despite the improvement in treatment options, chronic lymphocytic leukemia (CLL)
      remains an incurable disease and patients show a heterogeneous clinical course
      requiring therapy for many of them. In the current work, we have built a 20-gene
      expression (GE)-based risk score predictive for patients overall survival and
      improving risk classification using microarray gene expression data. GE-based
      risk score allowed identifying a high-risk group associated with a significant
      shorter overall survival (OS) and time to treatment (TTT) (P <= .01), comprising
      19.6% and 13.6% of the patients in two independent cohorts. GE-based risk score,
      and NRIP1 and TCF7 gene expression remained independent prognostic factors using
      multivariate Cox analyses and combination of GE-based risk score together with
      NRIP1 and TCF7 gene expression enabled the identification of three clinically
      distinct groups of CLL patients. Therefore, this GE-based risk score represents a
      powerful tool for risk stratification and outcome prediction of CLL patients and
      could thus be used to guide clinical and therapeutic decisions prospectively. 

PMID- 24883312
TI  - A novel stent coated with antibodies to endoglin inhibits neointimal formation of
      porcine coronary arteries.
AB  - Endoglin/CD105 is an accessory protein of the transforming growth factor-beta
      receptor system that plays a critical role in proliferation of endothelial cells
      and neovasculature. Here, we aimed to assess the effect of novel stents coated
      with antibodies to endoglin (ENDs) on coronary neointima formation. Thirty ENDs,
      thirty sirolimus-eluting stents (SESs), and thirty bare metal stents (BMSs) were
      randomly assigned and placed in the coronary arteries in 30 juvenile pigs.
      Histomorphometric analysis and scanning electron microscopy were performed after
      stent implantation. Our results showed that after 7 days, there was no difference
      in the neointimal area and percent area stenosis in ENDs compared with SMSs or
      BMSs. After 14 days, the neointima area and percent area stenosis in ENDs were
      markedly decreased than those in BMSs or SESs (P < 0.05). Moreover, the
      percentage of reendothelialization was significantly higher in ENDs than that in
      SESs or BMSs (P < 0.01) at 7 and 14 days. The artery injury and the inflammation
      scores were similar in all groups at 7 and 14 days. In conclusion, our results
      demonstrated for the first time to our knowledge that endoglin antibody-coated
      stents can markedly reduce restenosis by enhancing reendothelialization in the
      porcine model and potentially offer a new approach to prevent restenosis. 

PMID- 24883313
TI  - Erythropoietic potential of CD34+ hematopoietic stem cells from human cord blood
      and G-CSF-mobilized peripheral blood.
AB  - Red blood cell (RBC) supply for transfusion has been severely constrained by the
      limited availability of donor blood and the emergence of infection and
      contamination issues. Alternatively, hematopoietic stem cells (HSCs) from human
      organs have been increasingly considered as safe and effective blood source.
      Several methods have been studied to obtain mature RBCs from CD34+ hematopoietic
      stem cells via in vitro culture. Among them, human cord blood (CB) and
      granulocyte colony-stimulating factor-mobilized adult peripheral blood (mPB) are
      common adult stem cells used for allogeneic transplantation. Our present study
      focuses on comparing CB- and mPB-derived stem cells in differentiation from CD34+
      cells into mature RBCs. By using CD34+ cells from cord blood and G-CSF mobilized
      peripheral blood, we showed in vitro RBC generation of artificial red blood
      cells. Our results demonstrate that CB- and mPB-derived CD34+ hematopoietic stem
      cells have similar characteristics when cultured under the same conditions, but
      differ considerably with respect to expression levels of various genes and
      hemoglobin development. This study is the first to compare the characteristics of
      CB- and mPB-derived erythrocytes. The results support the idea that CB and mPB,
      despite some similarities, possess different erythropoietic potentials in in
      vitro culture systems. 

PMID- 24883314
TI  - Long-term anabolic androgenic steroid use is associated with increased atrial
      electromechanical delay in male bodybuilders.
AB  - We investigated the effect of long-term supraphysiologic doses of anabolic
      androgenic steroids (AAS) on atrial electromechanical delay (AEMD) in male
      bodybuilders. We clearly demonstrated that long-term consumption of
      supraphysiologic doses of AAS is associated with higher values of inter- and
      intra-AEMD in healthy young bodybuilders. 

PMID- 24883316
TI  - Radiographic outcomes of percutaneous pinning for displaced extra-articular
      fractures of the distal radius: a time course study.
AB  - INTRODUCTION: Although not all malunited distal radius fractures are symptomatic,
      the goal of treatment for displaced extra-articular fractures of the distal
      radius should be to restore and to maintain the radial geometry until bone
      healing. However, the time course change after surgery for these fractures is
      unclear. METHODS: We, therefore, performed a retrospective cohort study on
      patients who sustained such fractures treated with percutaneous pinning. The main
      outcome measures in this study included four radiographic measurements: radial
      height, radial inclination, radial tilt, and ulnar variance. RESULTS: Assessment
      of the monthly changes in these measurements revealed that early fracture
      collapse with loss of the reduced radial tilt occurred. Besides, among the 4
      measurements, the normal radial tilt was the most difficult to be achieved when
      repositioning and pinning the fractured fragments. CONCLUSIONS: Even though the
      modified Kapandji technique provided a superior ability to maintain the reduced
      position until bone healing over the Willenegger method, we recommended that
      refinement of surgical techniques and postoperative hand care program may be
      necessary to fulfill the treatment objectives of stable surgical fixation and
      early joint motion.

PMID- 24883317
TI  - Elevated serum vascular cell adhesion molecule-1 is associated with septic
      encephalopathy in adult community-onset severe sepsis patients.
AB  - BACKGROUND AND AIM: Septic encephalopathy (SE) is a common complication of severe
      sepsis. Increased concentrations of circulating soluble adhesion molecules are
      reported in septic patients. This study aimed to determine whether serum adhesion
      molecules are associated with SE. METHODS: Seventy nontraumatic, nonsurgical
      adult patients with severe sepsis admitted through ER were evaluated. Serum
      adhesion molecules were assessed for their relationship with SE, and compared
      with other clinical predictors and biomarkers. RESULTS: Twenty-three (32.8%)
      patients had SE. SE group had higher in-hospital mortality (40% versus 11%, P =
      0.009) and their sVCAM-1, sICAM-1, and lactate levels on admission were also
      higher than non-SE group. By stepwise logistic regression model, sVCAM-1, age,
      and maximum 24-hours SOFA score were independently associated with septic
      encephalopathy. The AUC analysis of ROC curve of different biomarkers showed that
      sVCAM-1 is better to predict SE. The sVCAM-1 levels in the SE group were
      significantly higher than those of the non-SE group at three time periods (Days
      1, 4, and 7). CONCLUSIONS: Septic encephalopathy implies higher mortality in
      nontraumatic, nonsurgical patients with severe sepsis. VCAM-1 level on
      presentation is a more powerful predictor of SE in these patients than lactate
      concentration and other adhesion molecules on admission.

PMID- 24883318
TI  - A simple and efficient method to isolate LTR sequences of plant retrotransposon.
AB  - Retrotransposons (RTNs) have important roles in the formation of plant genome
      size, structure, and evolution. Ubiquitous distributions, abundant copy numbers,
      high heterogeneities, and insertional polymorphisms of RTNs have made them as
      excellent sources for molecular markers development. However, the wide
      application of RTNs-based molecular markers is restricted by the scarcity of the
      LTR (long terminal repeat) sequences information. A new, simple, and efficient
      method to isolate LTR sequences of RTNs was presented based on the degenerate
      RNase H nested primers and PPT (polypurine tract) primer of RTNs in tree peony.
      This method combined the characteristics and advantages of high-efficiency
      thermal asymmetric interlaced PCR (hiTAIL-PCR), annealing control primer (ACP)
      system, and suppression PCR method. Nineteen LTR sequences were isolated using
      this new method in tree peony and the applicability of the LTR sequences based
      markers was validated by further SSAP analysis. The results showed that the new
      method is simple, of low-cost, and highly efficient, which is just conducted by
      three rounds of PCR and does not need any restriction enzymes and adapters, much
      less the hybridizations. This new method is rapid, economical, and cost- and time
      saving, which could be easily used to isolate LTR sequences of RTNs. 

PMID- 24883315
TI  - Fatty acids in energy metabolism of the central nervous system.
AB  - In this review, we analyze the current hypotheses regarding energy metabolism in
      the neurons and astroglia. Recently, it was shown that up to 20% of the total
      brain's energy is provided by mitochondrial oxidation of fatty acids. However,
      the existing hypotheses consider glucose, or its derivative lactate, as the only
      main energy substrate for the brain. Astroglia metabolically supports the neurons
      by providing lactate as a substrate for neuronal mitochondria. In addition, a
      significant amount of neuromediators, glutamate and GABA, is transported into
      neurons and also serves as substrates for mitochondria. Thus, neuronal
      mitochondria may simultaneously oxidize several substrates. Astrocytes have to
      replenish the pool of neuromediators by synthesis de novo, which requires large
      amounts of energy. In this review, we made an attempt to reconcile beta-oxidation
      of fatty acids by astrocytic mitochondria with the existing hypothesis on
      regulation of aerobic glycolysis. We suggest that, under condition of neuronal
      excitation, both metabolic pathways may exist simultaneously. We provide
      experimental evidence that isolated neuronal mitochondria may oxidize palmitoyl
      carnitine in the presence of other mitochondrial substrates. We also suggest that
      variations in the brain mitochondrial metabolic phenotype may be associated with
      different mtDNA haplogroups. 

PMID- 24883319
TI  - Does the addition of tramadol and ketamine to ropivacaine prolong the axillary
      brachial plexus block?
AB  - BACKGROUND AND OBJECTIVES: A prospective, randomized, controlled, double-blind
      clinical trial to assess the effect of tramadol and ketamine, 50 mg, added to
      ropivacaine in brachial plexus anesthesia. METHODS: Thirty-six ASA physical
      statuses I and II patients, between 18 and 60 years of age, scheduled for forearm
      and hand surgery under axillary brachial plexus block, were allocated to 3
      groups. Group R received 0.375% ropivacaine in 40 mL, group RT received 0.375%
      ropivacaine in 40 mL with 50 mg tramadol, and group RK received 0.375%
      ropivacaine in 40 mL with 50 mg ketamine for axillary brachial plexus block. The
      onset times and the duration of sensory and motor blocks, duration of analgesia,
      hemodynamic parameters, and adverse events (nausea, vomiting, and feeling
      uncomfortable) were recorded. RESULTS: The onset time of sensorial block was the
      fastest in ropivacaine + tramadol group. Duration of sensorial and motor block
      was the shortest in the ropivacaine + tramadol group. Duration of analgesia was
      significantly longer in ropivacaine + tramadol group. CONCLUSION: We conclude
      that when added to brachial plexus analgesia at a dose of 50 mg, tramadol extends
      the onset and duration time of the block and improves the quality of
      postoperative analgesia without any side effects.

PMID- 24883320
TI  - Intestinal parasites of owned dogs and cats from metropolitan and micropolitan
      areas: prevalence, zoonotic risks, and pet owner awareness in northern Italy.
AB  - Intestinal parasites of dogs and cats are cosmopolitan pathogens with zoonotic
      potential for humans. Our investigation considered their diffusion in dogs and
      cats from northern Italy areas, specifically the metropolitan area of Milan and
      two micropolitan areas of neighboring provinces. It included the study of the
      level of awareness in pet owners of the zoonotic potential from these parasites.
      A total of 409 fresh fecal samples were collected from household dogs and cats
      for copromicroscopic analysis and detection of Giardia duodenalis coproantigens.
      The assemblages of Giardia were also identified. A questionnaire about intestinal
      parasites biology and zoonotic potential was submitted to 185 pet owners. The
      overall prevalence of intestinal parasites resulted higher in cats (47.37%
      60.42%) and dogs (57.41%-43.02%) from micropolitan areas than that from the
      metropolis of Milan (dogs: P = 28.16%; cats: P = 32.58 %). The zoonotic parasites
      infecting pets under investigation were T. canis and T. cati, T. vulpis,
      Ancylostomatidae, and G. duodenalis assemblage A. Only 49.19% of pet owners
      showed to be aware of the risks for human health from canine and feline
      intestinal parasites. Parasitological results in pets and awareness determination
      in their owners clearly highlight how the role of veterinarians is important in
      indicating correct and widespread behaviors to reduce risks of infection for pets
      and humans in urban areas. 

PMID- 24883321
TI  - Cortisol is an associated-risk factor of brain dysfunction in patients with
      severe sepsis and septic shock.
AB  - OBJECTIVES: To investigate cortisol levels in brain dysfunction in patients with
      severe sepsis and septic shock. METHODS: In 128 septic and sedated patients, we
      studied brain dysfunction including delirium and coma by the evaluation of
      Richmond Agitation Sedation Scale (RASS), the Confusion Method Assessment in the
      ICU (CAM-ICU) after sedation withdrawal and the measurement of serum S100B
      biomarker of brain injury. Serum cortisol and S100B were measured within 12 hours
      after ICU admission and daily over the next four days. RESULTS: Brain dysfunction
      was observed in 50% (64/128) before but in 84% (107/128) of patients after
      sedation withdrawal, and was more common in the patients older than 57 years (P =
      0.009). Both cortisol (P = 0.007) and S100B levels (P = 0.028) were higher in
      patients with than patients without brain dysfunction. Cortisol levels were
      associated with ICU mortality (hazard ratio = 1.17, P = 0.024). Multivariate
      logistic regression showed that cortisol (odds ratio (OR): 2.34, 95% CI (2.01,
      3.22), P = 0.02) and the combination effect of cortisol with age (OR: 1.004, 95%
      CI (1.002, 1.93), P = 0.038) but not S100B were associated with brain
      dysfunction. CONCLUSIONS: Cortisol was an associated-risk factor of brain
      dysfunction in patients with severe sepsis and septic shock.

PMID- 24883322
TI  - The effect of autologous activated platelet rich plasma (AA-PRP) injection on
      pattern hair loss: clinical and histomorphometric evaluation.
AB  - To investigate the safety and clinical efficacy of AA-PRP injections for pattern
      hair loss. AA-PRP, prepared from a small volume of blood, was injected on half of
      the selected patients' scalps with pattern hair loss. The other half was treated
      with placebo. Three treatments were given for each patient, with intervals of 1
      month. The endpoints were hair re-growth, hair dystrophy as measured by
      dermoscopy, burning or itching sensation, and cell proliferation as measured by
      Ki-67 evaluation. At the end of the 3 cycles of treatment, the patients presented
      clinical improvement in the mean number of hairs, with a mean increase of 18.0
      hairs in the target area, and a mean increase in total hair density of 27.7 (
      number of hairs/cm(2)) compared with baseline values. Microscopic evaluation
      showed the increase of epidermis thickness and of the number of hair follicles
      two weeks after the last AA-PRP treatment compared to baseline value (P < 0.05).
      We also observed an increase of Ki67(+) keratinocytes of epidermis and of hair
      follicular bulge cells and a slight increase of small blood vessels around hair
      follicles in the treated skin compared to baseline (P < 0.05). 

PMID- 24883323
TI  - Biodegradable polyphosphazene biomaterials for tissue engineering and delivery of
      therapeutics.
AB  - Degradable biomaterials continue to play a major role in tissue engineering and
      regenerative medicine as well as for delivering therapeutic agents. Although the
      chemistry of polyphosphazenes has been studied extensively, a systematic review
      of their applications for a wide range of biomedical applications is lacking.
      Polyphosphazenes are synthesized through a relatively well-known two-step
      reaction scheme which involves the substitution of the initial linear precursor
      with a wide range of nucleophiles. The ease of substitution has led to the
      development of a broad class of materials that have been studied for numerous
      biomedical applications including as scaffold materials for tissue engineering
      and regenerative medicine. The objective of this review is to discuss the
      suitability of poly(amino acid ester)phosphazene biomaterials in regard to their
      unique stimuli responsive properties, tunable degradation rates and mechanical
      properties, as well as in vitro and in vivo biocompatibility. The application of
      these materials in areas such as tissue engineering and drug delivery is
      discussed systematically. Lastly, the utility of polyphosphazenes is further
      extended as they are being employed in blend materials for new applications and
      as another method of tailoring material properties. 

PMID- 24883324
TI  - Contemporary hearing rehabilitation options in patients with aural atresia.
AB  - Congenital aural atresia is the failure of development of the external auditory
      canal. It usually occurs in conjunction with microtia, which is the malformation
      of the auricle due to a failure of development of the external ear. Aural
      atresia, with or without microtia, may significantly affect the hearing and
      social life of the patients. It is important for every medical practitioner to be
      aware of the possible treatment options for hearing rehabilitation in this group
      of patients. In the era of modern technology, new choices, including Bone
      Anchored Hearing Aid (BAHA) (Cochlear Ltd. and Oticon Medical), Vibrant
      Soundbridge (VSB) (MED-EL, Innsbruck, Austria), and Bonebridge system (BB) (MED
      EL, Innsbruck, Austria), provide high-end alternatives to traditional Bone
      Conduction Hearing Aid and Auditory Canal Reconstruction. All these options have
      advantages and disadvantages, and they are appropriate for different patients
      and/or at different ages. This paper aims to provide an overview of the
      management of hearing rehabilitation in congenital aural atresia patients and a
      discussion of each treatment option. 

PMID- 24883326
TI  - Identification and characterization of the grape WRKY family.
AB  - WRKY transcription factors have functions in plant growth and development and in
      response to biotic and abiotic stresses. Many studies have focused on functional
      identification of WRKY transcription factors, but little is known about the
      molecular phylogeny or global expression patterns of the complete WRKY family. In
      this study, we identified 80 WRKY proteins encoded in the grape genome. Based on
      the structural features of these proteins, the grape WRKY genes were classified
      into three groups (groups 1-3). Analysis of WRKY genes expression profiles
      indicated that 28 WRKY genes were differentially expressed in response to biotic
      stress caused by grape whiterot and/or salicylic acid (SA). In that 16 WRKY genes
      upregulated both by whiterot pathogenic bacteria and SA. The results indicated
      that 16 WRKY proteins participated in SA-dependent defense signal pathway. This
      study provides a basis for cloning genes with specific functions from grape. 

PMID- 24883325
TI  - In vitro screening for beta-hydroxy-beta-methylglutaryl-CoA reductase inhibitory
      and antioxidant activity of sequentially extracted fractions of Ficus palmata
      Forsk.
AB  - Hypercholesterolemia-induced oxidative stress has been strongly implicated in the
      pathogenesis of atherosclerosis, which is one of the major causes of mortality
      worldwide. The current work, for the first time, accounts the antioxidant,
      genoprotective, antilipoperoxidative, and HMG-CoA reductase (EC 1.1.1.34)
      inhibitory properties of traditional medicinal plant, Ficus palmata Forsk. Our
      result showed that among sequentially extracted fractions of Ficus palmata Forsk,
      FPBA (F. palmata bark aqueous extract) and FPLM (F. palmata leaves methanolic
      extract) extracts have higher phenolic content and also exhibited significantly
      more radical scavenging (DPPH and Superoxide) and antioxidant (FRAP) capacity.
      Moreover, FPBA extract also exhibited significantly higher inhibition of lipid
      peroxidation assay. Additionally, results showed almost complete and partial
      protection of oxidatively damaged DNA by these plant extracts when compared to
      mannitol. Furthermore, our results showed that FPBA extract (IC50 = 9.1 +/- 0.61
      ug/mL) exhibited noteworthy inhibition of HMG-CoA reductase activity as compared
      to other extracts, which might suggest its role as cardioprotective agent. In
      conclusion, results showed that FPBA extract not only possess significant
      antioxidant and genoprotective property but also is able to attenuate the
      enzymatic activity of HMG-CoA reductase, which might suggest its role in
      combating various oxidative stress-related diseases, including atherosclerosis.

PMID- 24883327
TI  - Quantitative electroencephalography and behavioural correlates of daytime
      sleepiness in chronic stroke.
AB  - Sleepiness is common after stroke, but in contrast to its importance for
      rehabilitation, existing studies focus primarily on the acute state and often use
      subjective sleepiness measures only. We used quantitative electroencephalography
      (qEEG) to extract physiological sleepiness, as well as subjective reports, in
      response to motor-cognitive demand in stroke patients and controls. We
      hypothesised that (a) slowing of the EEG is chronically sustained after stroke;
      (b) increased power in lower frequencies and increased sleepiness are associated;
      and (c) sleepiness is modulated by motor-cognitive demand. QEEGs were recorded in
      32 chronic stroke patients and 20 controls using a Karolinska Drowsiness Test
      protocol administered before and after a motor priming task. Subjective
      sleepiness was measured using the Karolinska Sleepiness Scale. The findings
      showed that power density was significantly increased in delta and theta
      frequency bands over both hemispheres in patients which were not associated with
      subjective sleepiness ratings. This effect was not observed in controls. The
      motor priming task induced differential hemispheric effects with greater increase
      in low-frequency bands and presumably compensatory increases in higher frequency
      bands. The results indicate sustained slowing in the qEEG in chronic stroke, but
      in contrast to healthy controls, these changes are not related to perceived
      sleepiness. 

PMID- 24883328
TI  - Effects of freshwater pollution on the genetics of zebra mussels (Dreissena
      polymorpha) at the molecular and population level.
AB  - Revealing long-term effects of contaminants on the genetic structure of organisms
      inhabiting polluted environments should encompass analyses at the population,
      molecular, and cellular level. Following this concept, we studied the genetic
      constitution of zebra mussel populations from a polluted (Dp) and reference sites
      (Cl) at the river Drava, Croatia, and applied microsatellite and DNA damage
      analyses (Comet assay, micronucleus test (MNT)). Additionally, mussels from both
      populations were exposed to polluted wastewater in the laboratory for three days,
      and DNA damage was analyzed to evaluate acclimatization and genetic adaptation of
      the investigated populations to the polluted environment. The two populations
      differed in their genetic constitution. Microsatellite analysis suggested that Dp
      had undergone a genetic bottleneck. Comet assay did not indicate any difference
      in DNA damage between the two populations, but MNT revealed that Dp had an
      increased percentage of micronuclei in hemocytes in comparison to Cl. The
      laboratory experiment revealed that Dp had a lower percentage of tail DNA and a
      higher percentage of micronuclei than Cl. These differences between populations
      were possibly caused by an overall decreased fitness of Dp due to genetic drift
      and by an enhanced DNA repair mechanism due to acclimatization to pollution in
      the source habitat. 

PMID- 24883330
TI  - Atypical enteropathogenic Escherichia coli strains form biofilm on abiotic
      surfaces regardless of their adherence pattern on cultured epithelial cells.
AB  - The aim of this study was to determine the capacity of biofilm formation of
      atypical enteropathogenic Escherichia coli (aEPEC) strains on abiotic and biotic
      surfaces. Ninety-one aEPEC strains, isolated from feces of children with
      diarrhea, were analyzed by the crystal violet (CV) assay on an abiotic surface
      after 24 h of incubation. aEPEC strains representing each HEp-2 cell type of
      adherence were analyzed after 24 h and 6, 12, and 18 days of incubation at 37
      degrees C on abiotic and cell surfaces by CFU/cm(2) counting and confocal laser
      scanning microscopy (CLSM). Biofilm formation on abiotic surfaces occurred in 55
      (60.4%) of the aEPEC strains. There was no significant difference in biofilm
      biomass formation on an abiotic versus prefixed cell surface. The biofilms could
      be visualized by CLSM at various developmental stages. aEPEC strains are able to
      form biofilm on an abiotic surface with no association with their adherence
      pattern on HEp-2 cells with the exception of the strains expressing UND
      (undetermined adherence). This study revealed the capacity of adhesion and
      biofilm formation by aEPEC strains on abiotic and biotic surfaces, possibly
      playing a role in pathogenesis, mainly in cases of persistent diarrhea.

PMID- 24883329
TI  - CD163+ tumor-associated macrophages correlated with poor prognosis and cancer
      stem cells in oral squamous cell carcinoma.
AB  - Tumor-associated macrophages (TAMs) play an important role in the progression and
      prognostication of numerous cancers. However, the role and clinical significance
      of TAM markers in oral squamous cell carcinoma (OSCC) has not been elucidated.
      The present study was designed to investigate the correlation between the
      expression of TAM markers and pathological features in OSCC by tissue microarray.
      Tissue microarrays containing 16 normal oral mucosa, 6 oral epithelial dysplasia,
      and 43 OSCC specimens were studied by immunohistochemistry. We observed that the
      protein expression of the TAM markers CD68 and CD163 as well as the cancer stem
      cell (CSC) markers ALDH1, CD44, and SOX2 increased successively from the normal
      oral mucosa to OSCC. The expressions of CD68 and CD163 were significantly
      associated with lymph node status, and SOX2 was significantly correlated with
      pathological grade and lymph node status, whereas ALDH1 was correlated with tumor
      stage. Furthermore, CD68 was significantly correlated with CD163, SOX2, and ALDH1
      (P < 0.05). Kaplan-Meier analysis revealed that OSCC patients overexpressing
      CD163 had significantly worse overall survival (P < 0.05). TAM markers are
      associated with cancer stem cell marker and OSCC overall survival, suggesting
      their potential prognostic value in OSCC. 

PMID- 24883331
TI  - Assessment of acute oral and dermal toxicity of 2 ethyl-carbamates with activity
      against Rhipicephalus microplus in rats.
AB  - The acute oral and dermal toxicity of two new ethyl-carbamates (ethyl-4
      bromophenyl-carbamate and ethyl-4-chlorophenyl-carbamate) with ixodicide activity
      was determined in rats. The oral LD50 of each carbamate was 300 to 2000 mg/kg,
      and the dermal LD50 of each carbamate was >5000 mg/kg. Clinically, the surviving
      rats that had received oral doses of each carbamate showed decreased weight gain
      (P < 0.05) and had slight nervous system manifestations. These clinical signs
      were evident from the 300 mg/kg dose and were reversible, whereas the 2000 mg/kg
      dose caused severe damage and either caused their death or was motive for
      euthanasia. At necropsy, these rats had dilated stomachs and cecums with diffuse
      congestion, as well as moderate congestion of the liver. Histologically, the
      liver showed slight degenerative lesions, binucleated hepatocytes, focal
      coagulative necrosis, and congestion areas; the severity of the lesions increased
      with dosage. Furthermore, an slight increase in gamma-glutamyltransferase,
      lactate dehydrogenase, and creatinine was observed in the plasma. The dermal
      application of the maximum dose (5000 mg/kg) of each carbamate did not cause
      clinical manifestations or liver and skin alterations. This finding demonstrates
      that the carbamates under study have a low oral hazard and low acute dermal
      toxicity.

PMID- 24883332
TI  - JAK inhibitors: treatment efficacy and safety profile in patients with psoriasis.
AB  - Janus kinase (JAK) pathways are key mediators in the immunopathogenesis of
      psoriasis. Psoriasis treatment has evolved with the advent of targeted therapies,
      which inhibit specific components of the psoriasis proinflammatory cascade. JAK
      inhibitors have been studied in early phase trials for psoriasis patients, and
      the data are promising for these agents as potential treatment options.
      Tofacitinib, an oral or topically administered JAK1 and JAK3 inhibitor, and
      ruxolitinib, a topical JAK1 and JAK2 inhibitor, have been most extensively
      studied in psoriasis, and both improved clinical symptoms of psoriasis.
      Additional JAK1 or JAK3 inhibitors are being studied in clinical trials. In phase
      III trials for rheumatoid arthritis, tofacitinib was efficacious in patients with
      inadequate responses to tumor necrosis factor inhibitors, methotrexate
      monotherapy, or disease-modifying antirheumatic drugs. The results of phase III
      trials are pending for these therapies in psoriasis, and these agents may
      represent important alternatives for patients with inadequate responses to
      currently available agents. Further investigations with long-term clinical trials
      are necessary to verify their utility in psoriasis treatment and assess their
      safety in this patient population. 

PMID- 24883334
TI  - Influenza Virus H1N1 inhibition by serine protease inhibitor (serpin)
      antithrombin III.
AB  - Endogenous serine protease inhibitors (serpins) are anti-inflammatory mediators
      with multiple biologic functions. Serpins are also part of the early innate
      immune response to viral infection that includes mannose binding lectins, soluble
      CD14, defensins and antimicrobial peptides. Recently, serpin antithrombin III
      (ATIII) was shown to have broad-spectrum antiviral activity against HIV, HSV and
      HCV. We tested ATIII's antiviral activity against a variety of influenza virus
      strains. In our studies we found strong in vitro inhibition of influenza virus A
      H1N1 isolates. Our data also demonstrate that ATIII potency was more than 100
      fold that of ribavirin. We also found that inhibition was dependent on viral
      hemagglutinin with decreasing efficacy in the order of H1N1 > H3N2 > H5N1 >> Flu
      B. In vivo efficacy is currently still lacking demonstrating need for more
      advanced delivery methods for this biomolecule. Understanding how ATIII regulates
      influenza virus inhibition may reveal new avenues for therapeutic interventions.

PMID- 24883333
TI  - Anti-hnRNP B1 (RA33) autoantibodies are associated with the clinical phenotype in
      Russian patients with rheumatoid arthritis and systemic sclerosis.
AB  - Heterogeneous nuclear ribonucleoproteins (hnRNPs) are potent autoantigenic
      targets in systemic autoimmune rheumatic diseases (SARD). Loss of tolerance to
      the RA33 complex consisting of hnRNP A2 and its alternatively spliced variants B1
      and B2 has been the interest of rheumatologists. A novel ELISA for the detection
      of anti-hnRNP B1 autoantibodies has been developed to investigate the prevalence
      thereof in 397 patients with SARD, including patients with rheumatoid arthritis
      (RA), spondyloarthropathy (SPA), juvenile chronic arthritis, systemic lupus
      erythematosus (SLE), systemic sclerosis (SSc), and Sjogren's syndrome (SS), in
      comparison to 174 controls. Anti-hnRNP B1 autoantibodies were significantly more
      prevalent in patients with SARD than controls (47/397, 11.8% versus 2/174, 1.1%;
      P<0.001). In particular, anti-hnRNP B1 were found more frequently in the disease
      cohorts than in the controls and were present in 24/165 (14.5%) patients with RA,
      6/58 (10.3%) SPA, 11/65 (16.9%) SSc, and 4/50 (8.0%) SLE. In RA patients, anti
      hnRNP B1 autoantibodies correlated significantly with C-reactive protein levels
      and erythrocyte sedimentation rate, while in patients with SSc it was associated
      with features of arterial wall stiffness and presence of hypertension. Anti-hnRNP
      B1 autoantibodies occur in SARD and seem to be correlated with distinct clinical
      characteristics in patients with RA and SSc.

PMID- 24883335
TI  - Elementary Implantable Force Sensor: For Smart Orthopaedic Implants.
AB  - Implementing implantable sensors which are robust enough to maintain long term
      functionality inside the body remains a significant challenge. The ideal
      implantable sensing system is one which is simple and robust; free from
      batteries, telemetry, and complex electronics. We have developed an elementary
      implantable sensor for orthopaedic smart implants. The sensor requires no
      telemetry and no batteries to communicate wirelessly. It has no on-board signal
      conditioning electronics. The sensor itself has no electrical connections and
      thus does not require a hermetic package. The sensor is an elementary L-C
      resonator which can function as a simple force transducer by using a solid
      dielectric material of known stiffness between two parallel Archimedean coils.
      The operating characteristics of the sensors are predicted using a simplified,
      lumped circuit model. We have demonstrated sensor functionality both in air and
      in saline. Our preliminary data indicate that the sensor can be reasonably well
      modeled as a lumped circuit to predict its response to loading.

PMID- 24883336
TI  - MODEL-BASED LAMOTRIGINE CLEARANCE CHANGES DURING PREGNANCY: CLINICAL IMPLICATION.
AB  - OBJECTIVE: The objective of the study was to characterize changes in the oral
      clearance (CL/F) of lamotrigine (LTG) over the course of pregnancy and the
      postpartum period through a model-based approach incorporating clinical
      characteristics that may influence CL/F, in support of developing clinical
      management guidelines. METHODS: Women receiving LTG therapy who were pregnant or
      planning pregnancy were enrolled. Maternal blood samples were collected at each
      visit. A pharmacokinetic analysis was performed using a population-based,
      nonlinear, mixed-effects model. RESULTS: A total of 600 LTG concentrations from
      60 women (64 pregnancies) were included. The baseline LTG CL/F was 2.16 L/h with
      a between-subject variability of 40.6%. The influence of pregnancy on CL/F was
      described by gestational week. Two subpopulations of women emerged based on the
      rate of increase of LTG CL/F during pregnancy. The gestational age-associated
      increase in CL/F displayed a ten-fold higher rate in 77% of the women (0.118
      L/h/week) compared to 23% (0.0115 L/h/week). The between-subject variability in
      these slopes was 43.0%. The increased CL/F at delivery declined to baseline
      values with a half-life of 0.55 weeks. INTERPRETATION: The majority of women had
      a substantial increase in CL/F from 2.16 to 6.88 L/h by the end of pregnancy,
      whereas 23% of women had a minimal increase. An increase in CL/F may correspond
      to decreases in LTG blood concentrations necessitating the need for more frequent
      dosage adjustments and closer monitoring in some pregnant women with epilepsy.
      Postpartum doses should be tapered to preconception dose ranges within 3 weeks of
      delivery.

PMID- 24883337
TI  - beta1-adrenergic receptor activation enhances memory in Alzheimer's disease
      model.
AB  - OBJECTIVE: Deficits in social recognition and learning of social cues are major
      symptoms of neurodegenerative disorders such as Alzheimer's disease (AD). Here we
      studied the role of beta1-noradrenergic signaling in cognitive function to
      determine whether it could be used as a potential therapeutic target for AD.
      METHODS: Using pharmacological, biochemical and behavioral tools, we assessed
      social recognition and the beta1-adrenergic receptor (ADR) and its downstream
      PKA/phospho-CREB (pCREB) signaling cascade in the medial amygdala (MeA) in Thy1
      hAPPLond/Swe+(APP) mouse model of AD. RESULTS: Our results demonstrated that APP
      mice display a significant social recognition deficit which is dependent on the
      beta1-adrenergic system. Moreover, betaxolol, a selective beta1-ADR antagonist,
      impaired social but not object/odor learning in C57Bl/6 mice. Our results
      identifies activation of the PKA/pCREB downstream of beta1-ADR in MeA as
      responsible signaling cascade for learning of social cues in MeA. Finally, we
      found that xamoterol, a selective beta1-ADR partial agonist, rescued the social
      recognition deficit of APP mice by increasing nuclear pCREB. INTERPRETATION: Our
      data indicate that activation of beta1-ADR in MeA is essential for learning of
      social cues, and that an impairment of this cascade in AD may contribute to
      pathogenesis and cognitive deficits. Therefore, selective activation of beta1-ADR
      may be used as a therapeutic approach to rescue memory deficits in AD. Further
      safety and translational studies will be needed to ensure the safety of this
      approach.

PMID- 24883338
TI  - Teaching Goal-Setting for Weight-Gain Prevention in a College Population:
      Insights from the CHOICES Study.
AB  - PURPOSE: This article describes the effectiveness of goal setting instruction in
      the CHOICES (Choosing Healthy Options in College Environments and Settings)
      study, an intervention evaluating the effectiveness of weight gain prevention
      strategies for 2-year college students. METHODS: Four hundred and forty-one
      participants from three community colleges were recruited. Participants
      randomized into the intervention (n=224) enrolled in a course that taught
      strategies to help maintain or achieve a healthy weight. Participants were
      instructed in SMART (Specific, Measurable, Attainable, Realistic, Time-based) and
      behavioral goal-setting practices. Throughout the course, participants set goals
      related to improving their sleep, stress-management, exercise, and nutrition."
      RESULTS: Intervention participants set four hundred eighteen goals. Each goal was
      carefully evaluated. The efforts to teach behavioral goal-setting strategies were
      largely successful; however efforts to convey the intricacies of SMART goal
      setting were not as successful. CONCLUSIONS: Implications for effective teaching
      of skills in setting SMART behavioral goals were realized in this study. The
      insights gained from the goal-setting activities of this study could be used to
      guide educators who utilize goals to achieve health behavior change.
      RECOMMENDATIONS: Based on the results of this study, it is recommended that very
      clear and directed instruction be provided in addition to multiple opportunities
      for goal-setting practice. Implications for future interventions involving
      education about goal-setting activities are discussed.

PMID- 24883339
TI  - Evaluation of serum nitric oxide level in patients with oral lichen planus.
AB  - STATEMENT OF PROBLEM: Oral lichen planus (OLP) is a chronic inflammatory oral
      mucosal disease with indefinite etiology. In recent researches, free radicals
      have been deliberated as the possible etiology of inflammatory and autoimmune
      diseases. PURPOSE: This study was aimed to evaluate the stress oxidative status
      with the nitric oxide (NO) index in a sample of Iranian population. MATERIALS AND
      METHOD: In this descriptive-comparative study, serum NO level was assessed in 20
      OLP patients as the case group and 20 healthy individuals as the control group.
      Collected data were analyzed by adopting two Sample t-test, using SPSS 16
      software. The statistical significance level was set at p< 0.05. RESULTS: The
      mean serum NO levels in OLP patients and healthy controls were 17.1+/-3.4 ng/ml
      and 14.5+/-2.7 ng/ml respectively; which revealed a significant statistical
      difference (p= 0.009). CONCLUSION: The results of the current study with its
      limitation may support the premise that higher serum levels of NO in patients
      with OLP might activate the process of lymphocytes and cellular immunity system;
      hence, possibly endorsing the effect of serum NO in pathogenesis of lichen
      planus.

PMID- 24883340
TI  - Evaluation of the serum zinc level in erosive and non-erosive oral lichen planus.
AB  - STATEMENT OF PROBLEM: Lichen planus is a chronic inflammatory immunologic-based
      disease involving skin and mucosa. This disease is generally divided into two
      categories: erosive and non-erosive. Many etiologic factors are deliberated
      regarding the disease; however, the disorders of immune system and the role of
      cytotoxic T-lymphocytes and monocytes are more highlighted. Zinc is an imperative
      element for the growth of epithelium and its deficiency induces the cytotoxic
      activity of T-helper2 cells, which seems to be associated with lichen planus.
      PURPOSE: This study was aimed to evaluate the levels of serum zinc in erosive and
      non-erosive oral lichen planus (OLP) and to compare it with the healthy control
      group to find out any feasible inference. MATERIALS AND METHOD: A total of 22
      patients with erosive oral lichen planus, 22 patients with non erosive OLP and 44
      healthy individuals as the control group were recruited in this descriptive
      comparative study. All the participants were selected from the referees to the
      department of oral medicine, school of dentistry, Tabriz University of Medical
      Sciences. Serum zinc level was examined for all the individuals with liquid-stat
      kit (Beckman Instruments Inc.; Carlsbad, CA). Data were analyzed by adopting the
      ANOVA and Tukey tests, using SPSS 16 statistical software. RESULTS: The mean age
      of patients with erosive and non-erosive LP was 41.7 and 41.3 years,
      respectively. The mean age of the healthy control group was 34.4 years .The mean
      serum zinc levels in the erosive and non erosive lichen planus groups and control
      groups were 8.3 (1.15), 11.15 (0.92) and 15.74 (1.75) MUg/dl respectively. The
      difference was statistically significant (p< 0.05). CONCLUSION: The serum zinc
      levels were decreased in patients with erosive oral lichen planus. This finding
      may probably indicate the promising role of zinc in development of oral lichen
      planus.

PMID- 24883341
TI  - Evaluation of the antimicrobial effect of conventional and nanosilver-containing
      varnishes on oral streptococci.
AB  - STATEMENT OF THE PROBLEM: Nanosilver particles have the potential to serve as a
      bactericidal agent because of the inherent antimicrobial influences of silver
      ion. The literature confirmed that specific micro-organisms, especially
      streptococci, have an important role as an etiological factor for caries.
      PURPOSE: The aim of this study was to evaluate the antimicrobial effect of
      conventional and nanosilver-containing varnishes on oral streptococci. MATERIALS
      AND METHOD: Pure cultivations of Streptococcus mutans and Streptococcus
      salivarius were prepared on blood agar media. Thereafter, 0.5 McFarland standard
      of recently grown bacteria in normal saline was prepared and the bacteria were
      cultivated monotonously on the culture medium surface by applying a swab.
      Different concentrations of nanosilver varnishes were prepared in the Mueller-
      Hinton broth medium in the test tubes and equal amounts of 0.5 McFarland
      suspension of all the tested bacteria were added separately to all test tubes. A
      tube without varnish was included as the control sample. The tubes were kept at
      37 degrees C for 24 hours, then cultured to determine the numbers of bacteria in
      each tube by counting colonies. The numbers of bacteria in tubes with varnish
      were compared to the numbers of bacteria in the tube without varnish. In the
      instance of observing any reduction in the growth, the minimum inhibitory
      concentration for growth in the tube with varnish was determined. RESULTS:
      Nanosilver varnish had an antimicrobial effect on S. mutans and S. salivarius. 
      S. salivarius was more susceptible than S. mutans to the nanosilver varnish.
      CONCLUSION: Based on the results of this study, nanosilver varnishes can be used
      under amalgam restorations to reduce microbial population and subsequently
      preventing the recurrent caries.

PMID- 24883342
TI  - The effects of opaque and clear pit and fissure sealants on infrared laser
      fluorescence measurements.
AB  - STATEMENT OF THE PROBLEM: The purpose of placing sealants is to inhibit caries by
      physical closure of the pits and fissures of teeth. A device named DIAGNOdent is
      useful in detecting occlusal caries by employing laser fluorescence (LF).
      However, there are contradictory results in the influence of sealants on LF
      measurements. PURPOSE: The aim of this study is to investigate the effects of two
      different types of fissure sealants on LF measurements. MATERIALS AND METHOD: In
      this in vitro study, 86 extracted permanent third molars were divided randomly
      into two groups and clear or opaque sealant was applied on the occlusal surfaces.
      Two examiners performed pre- and post-seal fluorescence measurements twice with
      one week interval by employing DIAGNOdent device. Finally, measured values were
      evaluated through the statistical paired t-test by means of SPSS 17 software.
      RESULTS: The mean value of LF measurements increased significantly due to the
      application of clear sealant (p= 0.001) while the statistical changes in this
      measurement was negligible after applying opaque sealant (p= 0.311). CONCLUSION:
      Clear sealants increase the LF measured values but opaque sealants cause almost
      no changes. Therefore, DIAGNOdent device is not reliable for detecting caries
      beneath the clear sealant.

PMID- 24883343
TI  - The Relationship of Severe Early Childhood Caries and Body Mass Index in a Group
      of 3- to 6-year-old Children in Shiraz.
AB  - STATEMENT OF PROBLEM: Early childhood caries can cause pain, discomfort and also
      inability to have a healthy nutrition .Malnutrition can be characterized when
      there is a weight, height, and body mass index (BMI) deficiency. PURPOSE: The aim
      of this study was to evaluate the relationship between the severe early childhood
      caries (based on the dmft index) and BMI in pre-school children in Shiraz.
      MATERIALS AND METHOD: A descriptive analytical cross-sectional study was enrolled
      on 202 healthy preschool children with the age range of 3-6 years recruited from
      the kindergartens of different socio- economical parts of Shiraz, Iran. The
      Anthropometric measurements, weight and height were evaluated. The Z-scores were
      calculated employing WHO Anthro software (www.who.int/childgrowth/software/en/
      index.html) to elucidate the subject's status on the age- and sex-specific growth
      chart. Every Child who has received two Z-scores under the normal value (< -2)
      was considered as abnormal. The relationship between dmft index and BMI was then
      investigated. RESULTS: The mean of dmft was 4.13. From children with severe early
      childhood caries, 12.5%were under weight, 5% had height deficiency and 19.5% had
      BMI deficiency, however, there was no significant relationship between increasing
      dmft and the height, weight and BMI deficiency. CONCLUSION: There was not a
      linear correlation between severe early childhood caries and BMI, height, and
      weight deficiency. An incidence of 55% was yielded for severe early childhood
      caries which was an additional finding of this study.

PMID- 24883345
TI  - The Correlation between the Frequency of Oral Lesions and the Amount of Smokeless
      Tobacco Usage in Patients Referred to Oral Medicine Department of Zahedan Dental
      School.
AB  - STATEMENT OF PROBLEM: The increasing use of smokeless tobacco in the last 15
      years has motivated researchers to evaluate its impact on its user's health.
      PURPOSE: The aim of this study was to determine the frequency of oral lesions
      related to smokeless tobacco and any possible correlation between the frequency
      of oral lesions and the amount of usage in patients referred to Zahedan Dental
      School. MATERIALS AND METHOD: A total of 90 (77 male and 13 female) cases, all
      snuff consumers, were surveyed in this cross sectional study which was
      accomplished by employing questionnaires. The questionnaire included demographic
      information, type and amount of smokeless tobacco used and the location where it
      was placed in the mouth. The completion of the questionnaires was followed by
      oral clinical examinations of patients. The location of any lesion found in soft
      tissue, was recorded in questionnaire. RESULTS: The mean age for men and women
      was 47.7 and 55.61, respectively. A total of 38 cases (29 males, 9 females) were
      found to have oral lesions. 26 patients were using the snuff one pack per day.
      The common site of lesions was lower buccal sulcus. From 38 lesions, 32 lesions
      were found at the site of snuff placement. Most of the lesions were degree 1 and
      white in color. After taking biopsy from 32 lesions, 26 cases were detected as
      hyperkeratotic and 6 cases as epithelial dysplasia. CONCLUSION: This study showed
      that use of snuff is very common in Zahedan and usage of this material can
      produce oral lesions. There is not a significant correlation between the
      frequency of oral lesions and the amount of usage.

PMID- 24883346
TI  - Intraosseous mucoepidermoid carcinoma: report of two cases.
AB  - Intraosseous mucoepidermoid carcinoma is a rare tumor which affects women more
      than men and is more common in the mandible. The radiological examination reveals
      a well-defined unilocular or multilocular radiolucent lesion. This tumor may
      resemble a glandular odontogenic cyst, particularly in incisional biopsies. The
      accurate diagnosis of these lesions is imperative because the subsequent
      treatment of each lesion would be different. The purpose of this study is to
      report two cases of intraosseous mucoepidermoid carcinoma and explicate the
      differentiating criteria of this lesion from the glandular odontogenic cyst. 

PMID- 24883344
TI  - Effect of a home bleaching agent on the fracture toughness of resin composites,
      using short rod design.
AB  - STATEMENT OF PROBLEM: Resin composites are brittle materials and their major
      shortcomings are manifested in their sensitivity to flaws and defects. Although
      various mechanical properties of resin composites have been described, few
      studies are available on assessing the effect of bleaching agents on resin
      composites using the short rod design. PURPOSE: To place various resin composites
      into distilled water at 37 degrees C for 21 days and determine the effect of
      immersion time in distilled water, with and without exposure to 10% carbamide
      peroxide by employing short rod design fracture toughness test. MATERIALS AND
      METHOD: Specimens were prepared from three resin composites; Rok (SDI), Esthet
      (Dentsply), and Estelite (Tokuyama). For each material, a total of 24 disc-shaped
      specimens were prepared using a custom-made mould. Specimens were randomly
      divided into 3 groups of 8 and conditioned in 37 degrees C distilled water for
      either 24 hours, or 21 days. 21 day specimens were tested both with and without
      applying bleaching agent; Polanight (SDI). Study group specimens were bleached
      for 21 days, 2 hours a day. The specimens were loaded using a universal testing
      machine with a crosshead speed of 0.5 mm per minute. The maximum load at specimen
      failure was recorded and the KIc (MPa. M (0.5)) was calculated. RESULTS:
      Statistical analysis using two-way ANOVA showed a significant relationship
      between material and time (p< 0.05).Tukey's test showed that after 24 h of
      immersion in distilled water, Rok revealed the highest KIc followed by Esthet and
      Estelite. The bleaching agent significantly improved the fracture toughness
      values of Esthet while it decreased that of Estelite. CONCLUSION: The fracture
      toughness of the resin composites was affected by the bleaching agent and
      distilled water. In comparison with Rok and Estelite, fracture toughness of
      Esthet was increased due to aging and application of bleaching agent.

PMID- 24883347
TI  - A methodology for multihazards load combinations of earthquake and heavy trucks
      for bridges.
AB  - Issues of load combinations of earthquakes and heavy trucks are important
      contents in multihazards bridge design. Current load resistance factor design
      (LRFD) specifications usually treat extreme hazards alone and have no
      probabilistic basis in extreme load combinations. Earthquake load and heavy truck
      load are considered as random processes with respective characteristics, and the
      maximum combined load is not the simple superimposition of their maximum loads.
      Traditional Ferry Borges-Castaneda model that considers load lasting duration and
      occurrence probability well describes random process converting to random
      variables and load combinations, but this model has strict constraint in time
      interval selection to obtain precise results. Turkstra's rule considers one load
      reaching its maximum value in bridge's service life combined with another load
      with its instantaneous value (or mean value), which looks more rational, but the
      results are generally unconservative. Therefore, a modified model is presented
      here considering both advantages of Ferry Borges-Castaneda's model and Turkstra's
      rule. The modified model is based on conditional probability, which can convert
      random process to random variables relatively easily and consider the nonmaximum
      factor in load combinations. Earthquake load and heavy truck load combinations
      are employed to illustrate the model. Finally, the results of a numerical
      simulation are used to verify the feasibility and rationality of the model. 

PMID- 24883348
TI  - Carbon nanofibers modified graphite felt for high performance anode in high
      substrate concentration microbial fuel cells.
AB  - Carbon nanofibers modified graphite fibers (CNFs/GF) composite electrode was
      prepared for anode in high substrate concentration microbial fuel cells.
      Electrochemical tests showed that the CNFs/GF anode generated a peak current
      density of 2.42 mA cm(-2) at a low acetate concentration of 20 mM, which was 54%
      higher than that from bare GF. Increase of the acetate concentration to 80 mM, in
      which the peak current density of the CNFs/GF anode greatly increased and was up
      to 3.57 mA cm(-2), was seven times as that of GF anode. Morphology
      characterization revealed that the biofilms in the CNFs/GF anode were much denser
      than those in the bare GF. This result revealed that the nanostructure in the
      anode not only enhanced current generation but also could tolerate high substrate
      concentration.

PMID- 24883349
TI  - Global systems for mobile position tracking using Kalman and Lainiotis filters.
AB  - We present two time invariant models for Global Systems for Mobile (GSM) position
      tracking, which describe the movement in x-axis and y-axis simultaneously or
      separately. We present the time invariant filters as well as the steady state
      filters: the classical Kalman filter and Lainiotis Filter and the Join Kalman
      Lainiotis Filter, which consists of the parallel usage of the two classical
      filters. Various implementations are proposed and compared with respect to their
      behavior and to their computational burden: all time invariant and steady state
      filters have the same behavior using both proposed models but have different
      computational burden. Finally, we propose a Finite Impulse Response (FIR)
      implementation of the Steady State Kalman, and Lainiotis filters, which does not
      require previous estimations but requires a well-defined set of previous
      measurements. 

PMID- 24883350
TI  - Directional slack-based measure for the inverse data envelopment analysis.
AB  - A novel technique has been introduced in this research which lends its basis to
      the Directional Slack-Based Measure for the inverse Data Envelopment Analysis. In
      practice, the current research endeavors to elucidate the inverse directional
      slack-based measure model within a new production possibility set. On one
      occasion, there is a modification imposed on the output (input) quantities of an
      efficient decision making unit. In detail, the efficient decision making unit in
      this method was omitted from the present production possibility set but
      substituted by the considered efficient decision making unit while its input and
      output quantities were subsequently modified. The efficiency score of the entire
      DMUs will be retained in this approach. Also, there would be an improvement in
      the efficiency score. The proposed approach was investigated in this study with
      reference to a resource allocation problem. It is possible to simultaneously
      consider any upsurges (declines) of certain outputs associated with the efficient
      decision making unit. The significance of the represented model is accentuated by
      presenting numerical examples. 

PMID- 24883351
TI  - A secure and fair joint E-lottery protocol.
AB  - The attractive huge prize causes people to adore lotteries. Due to the very small
      probability of winning prizes, the players can enhance their probability of
      winning by using the method of joint purchase. In spite of many lottery schemes
      having been proposed, most e-lottery schemes focus on the players' privacy or
      computation overhead rather than support a joint purchase protocol on the
      Internet. In this paper, we use the multisignature and verifiable random function
      to construct a secure and fair joint e-lottery scheme. The players can check the
      lottery integrity, and the winning numbers can be verified publicly. 

PMID- 24883352
TI  - Vertical velocity distribution in open-channel flow with rigid vegetation.
AB  - In order to experimentally investigate the effects of rigid vegetation on the
      characteristics of flow, the vegetations were modeled by rigid cylindrical rod.
      Flow field is measured under the conditions of submerged rigid rod in flume with
      single layer and double layer vegetations. Experiments were performed for various
      spacings of the rigid rods. The vegetation models were aligned with the
      approaching flow in a rectangular channel. Vertical distributions of time
      averaged velocity at various streamwise distances were evaluated using an
      acoustic Doppler velocimeter (ADV). The results indicate that, in submerged
      conditions, it is difficult to described velocity distribution along the entire
      depth using unified function. The characteristic of vertical distribution of
      longitudinal velocity is the presence of inflection. Under the inflection, the
      line is convex and groove above inflection. The interaction of high and low
      momentum fluids causes the flow to fold and creates strong vortices within each
      mixing layer. Understanding the flow phenomena in the area surrounding the tall
      vegetation, especially in the downstream region, is very important when modeling
      or studying the riparian environment. ADV measures of rigid vegetation
      distribution of the flow velocity field can give people a new understanding. 

PMID- 24883353
TI  - A novel resource management method of providing operating system as a service for
      mobile transparent computing.
AB  - This paper presents a framework for mobile transparent computing. It extends the
      PC transparent computing to mobile terminals. Since resources contain different
      kinds of operating systems and user data that are stored in a remote server, how
      to manage the network resources is essential. In this paper, we apply the
      technologies of quick emulator (QEMU) virtualization and mobile agent for mobile
      transparent computing (MTC) to devise a method of managing shared resources and
      services management (SRSM). It has three layers: a user layer, a manage layer,
      and a resource layer. A mobile virtual terminal in the user layer and virtual
      resource management in the manage layer cooperate to maintain the SRSM function
      accurately according to the user's requirements. An example of SRSM is used to
      validate this method. Experiment results show that the strategy is effective and
      stable. 

PMID- 24883354
TI  - Gain enhancement of a multiband resonator using defected ground surface on epoxy
      woven glass material.
AB  - A multiband microstrip resonator is proposed in this study which is realized
      through a rectangular radiator with embedded symmetrical rectangular slots in it
      and a defected ground surface. The study is presented with detailed parametric
      analyses to understand the effect of various design parameters. The design and
      analyses are performed using the FIT based full-wave electromagnetic simulator
      CST microwave studio suite. With selected parameter values, the resonator showed
      a peak gain of 5.85 dBi at 5.2 GHz, 6.2 dBi at 8.3 GHz, 3.9 dBi at 9.5 GHz, 5.9
      dBi at 12.2 GHz, and 4.7 dBi at 14.6 GHz. Meanwhile, the main lobe magnitude and
      the 3 dB angular beam width are 6.2 dBi and 86 degrees , 5.9 dBi and 53.7 degrees
      , 8.5 dBi and 43.9 degrees , 8.6 dBi and 42.1 degrees , and 4.7 dBi and 30.1
      degrees , respectively, at the resonant frequencies. The overall resonator has a
      compact dimension of 0.52lambda  * 0.52lambda  * 0.027lambda at the lower
      resonant frequency. For practical validation, a lab prototype was built on a 1.6
      mm thick epoxide woven glass fabric dielectric material which is measured using a
      vector network analyzer and within an anechoic chamber. The comparison between
      the simulated and measured results showed a very good understanding, which
      implies the practical suitability of the proposed multiband resonator design.

PMID- 24883355
TI  - Experimental and numerical study on tensile strength of concrete under different
      strain rates.
AB  - The dynamic characterization of concrete is fundamental to understand the
      material behavior in case of heavy earthquakes and dynamic events. The
      implementation of material constitutive law is of capital importance for the
      numerical simulation of the dynamic processes as those caused by earthquakes.
      Splitting tensile concrete specimens were tested at strain rates of 10(-7) s(-1)
      to 10(-4) s(-1) in an MTS material test machine. Results of tensile strength
      versus strain rate are presented and compared with compressive strength and
      existing models at similar strain rates. Dynamic increase factor versus strain
      rate curves for tensile strength were also evaluated and discussed. The same
      tensile data are compared with strength data using a thermodynamic model. Results
      of the tests show a significant strain rate sensitive behavior, exhibiting
      dynamic tensile strength increasing with strain rate. In the quasistatic strain
      rate regime, the existing models often underestimate the experimental results.
      The thermodynamic theory for the splitting tensile strength of concrete
      satisfactorily describes the experimental findings of strength as effect of
      strain rates.

PMID- 24883356
TI  - Application of the artificial bee colony algorithm for solving the set covering
      problem.
AB  - The set covering problem is a formal model for many practical optimization
      problems. In the set covering problem the goal is to choose a subset of the
      columns of minimal cost that covers every row. Here, we present a novel
      application of the artificial bee colony algorithm to solve the non-unicost set
      covering problem. The artificial bee colony algorithm is a recent swarm
      metaheuristic technique based on the intelligent foraging behavior of honey bees.
      Experimental results show that our artificial bee colony algorithm is competitive
      in terms of solution quality with other recent metaheuristic approaches for the
      set covering problem. 

PMID- 24883358
TI  - iSentenizer-MU: multilingual sentence boundary detection model.
AB  - Sentence boundary detection (SBD) system is normally quite sensitive to genres of
      data that the system is trained on. The genres of data are often referred to the
      shifts of text topics and new languages domains. Although new detection models
      can be retrained for different languages or new text genres, previous model has
      to be thrown away and the creation process has to be restarted from scratch. In
      this paper, we present a multilingual sentence boundary detection system
      (iSentenizer-MU) for Danish, German, English, Spanish, Dutch, French, Italian,
      Portuguese, Greek, Finnish, and Swedish languages. The proposed system is able to
      detect the sentence boundaries of a mixture of different text genres and
      languages with high accuracy. We employ i (+)Learning algorithm, an incremental
      tree learning architecture, for constructing the system. iSentenizer-MU, under
      the incremental learning framework, is adaptable to text of different topics and
      Roman-alphabet languages, by merging new data into existing model to learn the
      new knowledge incrementally by revision instead of retraining. The system has
      been extensively evaluated on different languages and text genres and has been
      compared against two state-of-the-art SBD systems, Punkt and MaxEnt. The
      experimental results show that the proposed system outperforms the other systems
      on all datasets.

PMID- 24883357
TI  - Human behavior-based particle swarm optimization.
AB  - Particle swarm optimization (PSO) has attracted many researchers interested in
      dealing with various optimization problems, owing to its easy implementation, few
      tuned parameters, and acceptable performance. However, the algorithm is easy to
      trap in the local optima because of rapid losing of the population diversity.
      Therefore, improving the performance of PSO and decreasing the dependence on
      parameters are two important research hot points. In this paper, we present a
      human behavior-based PSO, which is called HPSO. There are two remarkable
      differences between PSO and HPSO. First, the global worst particle was introduced
      into the velocity equation of PSO, which is endowed with random weight which
      obeys the standard normal distribution; this strategy is conducive to trade off
      exploration and exploitation ability of PSO. Second, we eliminate the two
      acceleration coefficients c 1 and c 2 in the standard PSO (SPSO) to reduce the
      parameters sensitivity of solved problems. Experimental results on 28 benchmark
      functions, which consist of unimodal, multimodal, rotated, and shifted high
      dimensional functions, demonstrate the high performance of the proposed algorithm
      in terms of convergence accuracy and speed with lower computation cost. 

PMID- 24883359
TI  - Hybrid metaheuristics for solving a fuzzy single batch-processing machine
      scheduling problem.
AB  - This paper deals with a problem of minimizing total weighted tardiness of jobs in
      a real-world single batch-processing machine (SBPM) scheduling in the presence of
      fuzzy due date. In this paper, first a fuzzy mixed integer linear programming
      model is developed. Then, due to the complexity of the problem, which is NP-hard,
      we design two hybrid metaheuristics called GA-VNS and VNS-SA applying the
      advantages of genetic algorithm (GA), variable neighborhood search (VNS), and
      simulated annealing (SA) frameworks. Besides, we propose three fuzzy earliest due
      date heuristics to solve the given problem. Through computational experiments
      with several random test problems, a robust calibration is applied on the
      parameters. Finally, computational results on different-scale test problems are
      presented to compare the proposed algorithms. 

PMID- 24883360
TI  - Phylogenetic signals from Nepomorpha (Insecta: Hemiptera: Heteroptera)
      mouthparts: stylets bundle, sense organs, and labial segments.
AB  - The present study is a cladistic analysis of morphological characters focusing on
      the file of the mandible, the apices of the maxillae, the rupturing device on the
      maxillae, the internal structures of the mouthparts, and the external morphology
      of the labial segments as well as the distribution of labial sensilla in true
      water bugs (Hemiptera: Heteroptera, infraorder Nepomorpha). The study is based on
      data referring to sixty-two species representing all nepomorphan families
      (Heteroptera), together with one outgroup species representing the infraorders
      Gerromorpha (Mesoveliidae). The morphological data matrix consists of forty-eight
      characters. The present hypothesis supports the monophyly of the Nepomorpha and
      the monophyly of all families. The new modification in the systematic
      classification has been proposed: ((Nepidae + Belostomatidae), (Diaprepocoridae +
      Corixidae + Micronectidae), (Ochteridae + Gelastocoridae), Aphelocheiridae,
      Potamocoridae, Naucoridae, Notonectidae, and (Pleidae + Helotrephidae)).

PMID- 24883361
TI  - Development of biological movement recognition by interaction between active
      basis model and fuzzy optical flow division.
AB  - Following the study on computational neuroscience through functional magnetic
      resonance imaging claimed that human action recognition in the brain of mammalian
      pursues two separated streams, that is, dorsal and ventral streams. It follows up
      by two pathways in the bioinspired model, which are specialized for motion and
      form information analysis (Giese and Poggio 2003). Active basis model is used to
      form information which is different from orientations and scales of Gabor
      wavelets to form a dictionary regarding object recognition (human). Also
      biologically movement optic-flow patterns utilized. As motion information guides
      share sketch algorithm in form pathway for adjustment plus it helps to prevent
      wrong recognition. A synergetic neural network is utilized to generate prototype
      templates, representing general characteristic form of every class. Having
      predefined templates, classifying performs based on multitemplate matching. As
      every human action has one action prototype, there are some overlapping and
      consistency among these templates. Using fuzzy optical flow division scoring can
      prevent motivation for misrecognition. We successfully apply proposed model on
      the human action video obtained from KTH human action database. Proposed approach
      follows the interaction between dorsal and ventral processing streams in the
      original model of the biological movement recognition. The attained results
      indicate promising outcome and improvement in robustness using proposed approach.

PMID- 24883362
TI  - Distributed SLAM using improved particle filter for mobile robot localization.
AB  - The distributed SLAM system has a similar estimation performance and requires
      only one-fifth of the computation time compared with centralized particle filter.
      However, particle impoverishment is inevitably because of the random particles
      prediction and resampling applied in generic particle filter, especially in SLAM
      problem that involves a large number of dimensions. In this paper, particle
      filter use in distributed SLAM was improved in two aspects. First, we improved
      the important function of the local filters in particle filter. The adaptive
      values were used to replace a set of constants in the computational process of
      importance function, which improved the robustness of the particle filter.
      Second, an information fusion method was proposed by mixing the innovation method
      and the number of effective particles method, which combined the advantages of
      these two methods. And this paper extends the previously known convergence
      results for particle filter to prove that improved particle filter converges to
      the optimal filter in mean square as the number of particles goes to infinity.
      The experiment results show that the proposed algorithm improved the virtue of
      the DPF-SLAM system in isolate faults and enabled the system to have a better
      tolerance and robustness. 

PMID- 24883363
TI  - A walk-in screening of dementia in the general population in Taiwan.
AB  - Alzheimer's disease (AD) has increased in its prevalence due to the increasing
      aged population. Currently there is no updated data on the prevalence of dementia
      including its very mild stage in Taiwan. Under the extensive coverage of
      Mentality Protection Center (MPC), Fo Guang Shan, Taiwan, the volunteers of MPC
      have conducted the medicine-related services and the screening of dementia by AD8
      (ascertainment of dementia 8) that can screen the dementia even at its very mild
      stage in general population in all Taiwan. From 2011 to 2013, in total, 2,171
      participants, 368 in the northern, 549 in the central, 877 in the southern, and
      377 in the eastern part, were recruited with the mean age being 66.9 +/- 10.2
      years old. The ratio of suspected dementia patients, AD8 score greater than or
      equal to 2, was 13.6% of all recruited participants with their mean AD8 score
      being 2.9 +/- 1.3, mean age being 69.4 +/- 10.8 years old, and female
      predominance being 73.0%. Although this is a screening study, it has extensive
      coverage of all Taiwan and the use of AD8 is capable of screening very mild
      dementia. A further study with a randomized sampling to examine the prevalence
      and incidence of dementia including its very mild stage is encouraged. 

PMID- 24883364
TI  - Four-wave mixing crosstalk suppression based on the pairing combinations of
      differently linear-polarized optical signals.
AB  - A new approach to suppressing the four-wave mixing (FWM) crosstalk by using the
      pairing combinations of differently linear-polarized optical signals was
      investigated. The simulation was conducted using a four-channel system, and the
      total data rate was 40 Gb/s. A comparative study on the suppression of FWM for
      existing and suggested techniques was conducted by varying the input power from 2
      dBm to 14 dBm. The robustness of the proposed technique was examined with two
      types of optical fiber, namely, single-mode fiber (SMF) and dispersion-shifted
      fiber (DSF). The FWM power drastically reduced to less than -68 and -25 dBm at an
      input power of 14 dBm, when the polarization technique was conducted for SMF and
      DSF, respectively. With the conventional method, the FWM powers were,
      respectively, -56 and -20 dBm. The system performance greatly improved with the
      proposed polarization approach, where the bit error rates (BERs) at the first
      channel were 2.57 * 10(-40) and 3.47 * 10(-29) at received powers of -4.90 and 
      13.84 dBm for SMF and DSF, respectively.

PMID- 24883365
TI  - Modeling of steam distillation mechanism during steam injection process using
      artificial intelligence.
AB  - Steam distillation as one of the important mechanisms has a great role in oil
      recovery in thermal methods and so it is important to simulate this process
      experimentally and theoretically. In this work, the simulation of steam
      distillation is performed on sixteen sets of crude oil data found in the
      literature. Artificial intelligence (AI) tools such as artificial neural network
      (ANN) and also adaptive neurofuzzy interference system (ANFIS) are used in this
      study as effective methods to simulate the distillate recoveries of these sets of
      data. Thirteen sets of data were used to train the models and three sets were
      used to test the models. The developed models are highly compatible with respect
      to input oil properties and can predict the distillate yield with minimum entry.
      For showing the performance of the proposed models, simulation of steam
      distillation is also done using modified Peng-Robinson equation of state.
      Comparison between the calculated distillates by ANFIS and neural network models
      and also equation of state-based method indicates that the errors of the ANFIS
      model for training data and test data sets are lower than those of other methods.

PMID- 24883366
TI  - Nature and properties of lateritic soils derived from different parent materials
      in Taiwan.
AB  - The objective of this study was to investigate the physical, chemical, and
      mineralogical composition of lateritic soils in order to use these soils as
      potential commercial products for industrial application in the future. Five
      lateritic soils derived from various parent materials in Taiwan, including
      andesite, diluvium, shale stone, basalt, and Pleistocene deposit, were collected
      from the Bt1 level of soil samples. Based on the analyses, the Tungwei soil is an
      alfisol, whereas other lateritic soils are ultisol. Higher pH value of Tungwei is
      attributed to the large amounts of Ca(2+) and Mg(2+). Loupi and Pingchen soils
      would be the older lateritic soils because of the lower active iron ratio. For
      the iron minerals, the magnetic iron oxides such as major amounts of magnetite
      and maghemite were found for Tamshui and Tungwei lateritic soils, respectively.
      Lepidocrocite was only found in Soka soil and intermediate amounts of goethite
      were detected for Loupi and Pingchen soils. After Mg-saturated and K-saturated
      processes, major amounts of mixed layer were observed in Loupi and Soka soils,
      whereas the montmorillonite was only detected in Tungwei soil. The investigation
      results revealed that the parent materials would play an important role during
      soil weathering process and physical, chemical, and mineralogy compositions
      strongly affect the formation of lateritic soils. 

PMID- 24883367
TI  - Distributed leader-following finite-time consensus control for linear multiagent
      systems under switching topology.
AB  - This paper investigates the finite-time consensus problem of leader-following
      multiagent systems. The dynamical models for all following agents and the leader
      are assumed the same general form of linear system, and the interconnection
      topology among the agents is assumed to be switching and undirected. We mostly
      consider the continuous-time case. By assuming that the states of neighbouring
      agents are known to each agent, a sufficient condition is established for finite
      time consensus via a neighbor-based state feedback protocol. While the states of
      neighbouring agents cannot be available and only the outputs of neighbouring
      agents can be accessed, the distributed observer-based consensus protocol is
      proposed for each following agent. A sufficient condition is provided in terms of
      linear matrix inequalities to design the observer-based consensus protocol, which
      makes the multiagent systems achieve finite-time consensus under switching
      topologies. Then, we discuss the counterparts for discrete-time case. Finally, we
      provide an illustrative example to show the effectiveness of the design approach.

PMID- 24883368
TI  - Modeling and analysis of mobility management in mobile communication networks.
AB  - Many strategies have been proposed to reduce the mobility management cost in
      mobile communication networks. This paper studies the zone-based registration
      methods that have been adopted by most mobile communication networks. We focus on
      two special zone-based registration methods, called two-zone registration (2Z)
      and two-zone registration with implicit registration by outgoing calls (2Zi). We
      provide a new mathematical model to analyze the exact performance of 2Z and 2Zi.
      We also present various numerical results, to compare the performance of 2Zi with
      those of 2Z and one-zone registration (1Z), and show that 2Zi is superior to 2Z
      as well as 1Z in most cases. 

PMID- 24883369
TI  - An investigation of generalized differential evolution metaheuristic for
      multiobjective optimal crop-mix planning decision.
AB  - This paper presents an annual multiobjective crop-mix planning as a problem of
      concurrent maximization of net profit and maximization of crop production to
      determine an optimal cropping pattern. The optimal crop production in a
      particular planting season is a crucial decision making task from the
      perspectives of economic management and sustainable agriculture. A multiobjective
      optimal crop-mix problem is formulated and solved using the generalized
      differential evolution 3 (GDE3) metaheuristic to generate a globally optimal
      solution. The performance of the GDE3 metaheuristic is investigated by comparing
      its results with the results obtained using epsilon constrained and nondominated
      sorting genetic algorithms-being two representatives of state-of-the-art in
      evolutionary optimization. The performance metrics of additive epsilon,
      generational distance, inverted generational distance, and spacing are considered
      to establish the comparability. In addition, a graphical comparison with respect
      to the true Pareto front for the multiobjective optimal crop-mix planning problem
      is presented. Empirical results generally show GDE3 to be a viable alternative
      tool for solving a multiobjective optimal crop-mix planning problem. 

PMID- 24883370
TI  - Visual quality assessment after network transmission incorporating NS2 and
      Evalvid.
AB  - On the basis of Evalvid tool integrated in NS2 (Network Simulator version 2), the
      paper gets new set of tools, myEvalvid, to establish the simulation and
      evaluation platform for multimedia transmission. Then the paper investigates the
      effects of various influence factors when multimedia information is transmitted
      in the network and the relationships among these factors. Based on the analysis,
      the paper gets different evaluation models, respectively. In this paper, we study
      the impact on performance of several basic source and network parameters of video
      streams, namely, GOP (Group of Pictures) pattern, compression quantitative
      parameters, packet length, and packet error rate. Simulation results show that
      different parameters lead to different distortion levels which are calculated
      according to the reconstruction images at the receiver and the original images.
      The experimental results show that the video transmission and quality evaluation
      model we designed can evaluate multimedia transmission performance over complex
      environment very well. 

PMID- 24883371
TI  - Evolutionary computation with spatial receding horizon control to minimize
      network coding resources.
AB  - The minimization of network coding resources, such as coding nodes and links, is
      a challenging task, not only because it is a NP-hard problem, but also because
      the problem scale is huge; for example, networks in real world may have thousands
      or even millions of nodes and links. Genetic algorithms (GAs) have a good
      potential of resolving NP-hard problems like the network coding problem (NCP),
      but as a population-based algorithm, serious scalability and applicability
      problems are often confronted when GAs are applied to large- or huge-scale
      systems. Inspired by the temporal receding horizon control in control
      engineering, this paper proposes a novel spatial receding horizon control (SRHC)
      strategy as a network partitioning technology, and then designs an efficient GA
      to tackle the NCP. Traditional network partitioning methods can be viewed as a
      special case of the proposed SRHC, that is, one-step-wide SRHC, whilst the method
      in this paper is a generalized N-step-wide SRHC, which can make a better use of
      global information of network topologies. Besides the SRHC strategy, some useful
      designs are also reported in this paper. The advantages of the proposed SRHC and
      GA for the NCP are illustrated by extensive experiments, and they have a good
      potential of being extended to other large-scale complex problems. 

PMID- 24883372
TI  - Effects of thinning intensities on soil infiltration and water storage capacity
      in a Chinese pine-oak mixed forest.
AB  - Thinning is a crucial practice in the forest ecosystem management. The soil
      infiltration rate and water storage capacity of pine-oak mixed forest under three
      different thinning intensity treatments (15%, 30%, and 60%) were studied in
      Qinling Mountains of China. The thinning operations had a significant influence
      on soil infiltration rate and water storage capacity. The soil infiltration rate
      and water storage capacity in different thinning treatments followed the order of
      control (nonthinning): <60%, <15%, and <30%. It demonstrated that thinning
      operation with 30% intensity can substantially improve soil infiltration rate and
      water storage capacity of pine-oak mixed forest in Qinling Mountains. The soil
      initial infiltration rate, stable infiltration rate, and average infiltration
      rate in thinning 30% treatment were significantly increased by 21.1%, 104.6%, and
      60.9%, compared with the control. The soil maximal water storage capacity and
      noncapillary water storage capacity in thinning 30% treatment were significantly
      improved by 20.1% and 34.3% in contrast to the control. The soil infiltration
      rate and water storage capacity were significantly higher in the surface layer
      (0~20 cm) than in the deep layers (20~40 cm and 40~60 cm). We found that the soil
      property was closely related to soil infiltration rate and water storage
      capacity.

PMID- 24883374
TI  - An optimal control strategy for DC bus voltage regulation in photovoltaic system
      with battery energy storage.
AB  - This paper presents an evaluation of an optimal DC bus voltage regulation
      strategy for grid-connected photovoltaic (PV) system with battery energy storage
      (BES). The BES is connected to the PV system DC bus using a DC/DC buck-boost
      converter. The converter facilitates the BES power charge/discharge to compensate
      for the DC bus voltage deviation during severe disturbance conditions. In this
      way, the regulation of DC bus voltage of the PV/BES system can be enhanced as
      compared to the conventional regulation that is solely based on the voltage
      sourced converter (VSC). For the grid side VSC (G-VSC), two control methods,
      namely, the voltage-mode and current-mode controls, are applied. For control
      parameter optimization, the simplex optimization technique is applied for the G
      VSC voltage- and current-mode controls, including the BES DC/DC buck-boost
      converter controllers. A new set of optimized parameters are obtained for each of
      the power converters for comparison purposes. The PSCAD/EMTDC-based simulation
      case studies are presented to evaluate the performance of the proposed optimized
      control scheme in comparison to the conventional methods. 

PMID- 24883373
TI  - New developments in scheduling applications.

PMID- 24883375
TI  - A novel approach toward fuzzy generalized bi-ideals in ordered semigroups.
AB  - In several advanced fields like control engineering, computer science, fuzzy
      automata, finite state machine, and error correcting codes, the use of fuzzified
      algebraic structures especially ordered semigroups plays a central role. In this
      paper, we introduced a new and advanced generalization of fuzzy generalized bi
      ideals of ordered semigroups. These new concepts are supported by suitable
      examples. These new notions are the generalizations of ordinary fuzzy generalized
      bi-ideals of ordered semigroups. Several fundamental theorems of ordered
      semigroups are investigated by the properties of these newly defined fuzzy
      generalized bi-ideals. Further, using level sets, ordinary fuzzy generalized bi
      ideals are linked with these newly defined ideals which is the most significant
      part of this paper. 

PMID- 24883376
TI  - Optimized scheduling technique of null subcarriers for peak power control in 3GPP
      LTE downlink.
AB  - Orthogonal frequency division multiple access (OFDMA) is a key multiple access
      technique for the long term evolution (LTE) downlink. However, high peak-to
      average power ratio (PAPR) can cause the degradation of power efficiency. The
      well-known PAPR reduction technique, dummy sequence insertion (DSI), can be a
      realistic solution because of its structural simplicity. However, the large usage
      of subcarriers for the dummy sequences may decrease the transmitted data rate in
      the DSI scheme. In this paper, a novel DSI scheme is applied to the LTE system.
      Firstly, we obtain the null subcarriers in single-input single-output (SISO) and
      multiple-input multiple-output (MIMO) systems, respectively; then, optimized
      dummy sequences are inserted into the obtained null subcarrier. Simulation
      results show that Walsh-Hadamard transform (WHT) sequence is the best for the
      dummy sequence and the ratio of 16 to 20 for the WHT and randomly generated
      sequences has the maximum PAPR reduction performance. The number of near optimal
      iteration is derived to prevent exhausted iterations. It is also shown that there
      is no bit error rate (BER) degradation with the proposed technique in LTE
      downlink system. 

PMID- 24883379
TI  - Experimental realization of a multiscroll chaotic oscillator with optimal maximum
      Lyapunov exponent.
AB  - Nowadays, different kinds of experimental realizations of chaotic oscillators
      have been already presented in the literature. However, those realizations do not
      consider the value of the maximum Lyapunov exponent, which gives a quantitative
      measure of the grade of unpredictability of chaotic systems. That way, this paper
      shows the experimental realization of an optimized multiscroll chaotic oscillator
      based on saturated function series. First, from the mathematical description
      having four coefficients (a, b, c, d1 ), an optimization evolutionary algorithm
      varies them to maximize the value of the positive Lyapunov exponent. Second, a
      realization of those optimized coefficients using operational amplifiers is
      given. Herein a, b, c, d1 are implemented with precision potentiometers to tune
      up to four decimals of the coefficients having the range between 0.0001 and
      1.0000. Finally, experimental results of the phase-space portraits for generating
      from 2 to 10 scrolls are listed to show that their associated value for the
      optimal maximum Lyapunov exponent increases by increasing the number of scrolls,
      thus guaranteeing a more complex chaotic behavior. 

PMID- 24883378
TI  - Detection of burst suppression patterns in EEG using recurrence rate.
AB  - Burst suppression is a unique electroencephalogram (EEG) pattern commonly seen in
      cases of severely reduced brain activity such as overdose of general anesthesia.
      It is important to detect burst suppression reliably during the administration of
      anesthetic or sedative agents, especially for cerebral-protective treatments in
      various neurosurgical diseases. This study investigates recurrent plot (RP)
      analysis for the detection of the burst suppression pattern (BSP) in EEG. The RP
      analysis is applied to EEG data containing BSPs collected from 14 patients.
      Firstly we obtain the best selection of parameters for RP analysis. Then, the
      recurrence rate (RR), determinism (DET), and entropy (ENTR) are calculated. Then
      RR was selected as the best BSP index one-way analysis of variance (ANOVA) and
      multiple comparison tests. Finally, the performance of RR analysis is compared
      with spectral analysis, bispectral analysis, approximate entropy, and the
      nonlinear energy operator (NLEO). ANOVA and multiple comparison tests showed that
      the RR could detect BSP and that it was superior to other measures with the
      highest sensitivity of suppression detection (96.49%, P = 0.03). Tracking BSP
      patterns is essential for clinical monitoring in critically ill and anesthetized
      patients. The purposed RR may provide an effective burst suppression detector for
      developing new patient monitoring systems. 

PMID- 24883380
TI  - Effect analysis of design variables on the disc in a double-eccentric butterfly
      valve.
AB  - We have performed a shape optimization of the disc in an industrial double
      eccentric butterfly valve using the effect analysis of design variables to
      enhance the valve performance. For the optimization, we select three performance
      quantities such as pressure drop, maximum stress, and mass (weight) as the
      responses and three dimensions regarding the disc shape as the design variables.
      Subsequently, we compose a layout of orthogonal array (L16) by performing
      numerical simulations on the flow and structure using a commercial package, ANSYS
      v13.0, and then make an effect analysis of the design variables on the responses
      using the design of experiments. Finally, we formulate a multiobjective function
      consisting of the three responses and then propose an optimal combination of the
      design variables to maximize the valve performance. Simulation results show that
      the disc thickness makes the most significant effect on the performance and the
      optimal design provides better performance than the initial design. 

PMID- 24883377
TI  - Endocrinopathies after allogeneic and autologous transplantation of hematopoietic
      stem cells.
AB  - Early and late endocrine disorders are among the most common complications in
      survivors after hematopoietic allogeneic- (allo-) and autologous- (auto-) stem
      cell transplant (HSCT). This review summarizes main endocrine disorders reported
      in literature and observed in our center as consequence of auto- and allo-HSCT
      and outlines current options for their management. Gonadal impairment has been
      found early in approximately two-thirds of auto- and allo-HSCT patients: 90-99%
      of women and 60-90% of men. Dysfunctions of the hypothalamus-pituitary-growth
      hormone/insulin growth factor-I axis, hypothalamus-pituitary-thyroid axis, and
      hypothalamus-pituitary-adrenal axis were documented as later complicances,
      occurring in about 10, 30, and 40-50% of transplanted patients, respectively.
      Moreover, overt or subclinical thyroid complications (including persistent low-T3
      syndrome, chronic thyroiditis, subclinical hypo- or hyperthyroidism, and thyroid
      carcinoma), gonadal failure, and adrenal insufficiency may persist many years
      after HSCT. Our analysis further provides evidence that main recognized risk
      factors for endocrine complications after HSCT are the underlying disease,
      previous pretransplant therapies, the age at HSCT, gender, total body
      irradiation, posttransplant derangement of immune system, and in the allogeneic
      setting, the presence of graft-versus-host disease requiring prolonged steroid
      treatment. Early identification of endocrine complications can greatly improve
      the quality of life of long-term survivors after HSCT. 

PMID- 24883381
TI  - Knowledge and asset management in sustainable civil engineering.

PMID- 24883383
TI  - Using fuzzy logic in test case prioritization for regression testing programs
      with assertions.
AB  - Program assertions have been recognized as a supporting tool during software
      development, testing, and maintenance. Therefore, software developers place
      assertions within their code in positions that are considered to be error prone
      or that have the potential to lead to a software crash or failure. Similar to any
      other software, programs with assertions must be maintained. Depending on the
      type of modification applied to the modified program, assertions also might have
      to undergo some modifications. New assertions may also be introduced in the new
      version of the program, while some assertions can be kept the same. This paper
      presents a novel approach for test case prioritization during regression testing
      of programs that have assertions using fuzzy logic. The main objective of this
      approach is to prioritize the test cases according to their estimated potential
      in violating a given program assertion. To develop the proposed approach, we
      utilize fuzzy logic techniques to estimate the effectiveness of a given test case
      in violating an assertion based on the history of the test cases in previous
      testing operations. We have conducted a case study in which the proposed approach
      is applied to various programs, and the results are promising compared to
      untreated and randomly ordered test cases. 

PMID- 24883382
TI  - Global optimization ensemble model for classification methods.
AB  - Supervised learning is the process of data mining for deducing rules from
      training datasets. A broad array of supervised learning algorithms exists, every
      one of them with its own advantages and drawbacks. There are some basic issues
      that affect the accuracy of classifier while solving a supervised learning
      problem, like bias-variance tradeoff, dimensionality of input space, and noise in
      the input data space. All these problems affect the accuracy of classifier and
      are the reason that there is no global optimal method for classification. There
      is not any generalized improvement method that can increase the accuracy of any
      classifier while addressing all the problems stated above. This paper proposes a
      global optimization ensemble model for classification methods (GMC) that can
      improve the overall accuracy for supervised learning problems. The experimental
      results on various public datasets showed that the proposed model improved the
      accuracy of the classification models from 1% to 30% depending upon the algorithm
      complexity. 

PMID- 24883384
TI  - Joint power and multiple access control for wireless mesh network with Rose
      projection method.
AB  - This paper investigates the utility maximization problem for the downlink of the
      multi-interface multichannel wireless mesh network with orthogonal frequency
      division multiple access. A cross-layer joint power and multiple access control
      algorithm are proposed. Rosen projection matrix is combined with Solodov
      projection techniques to build a three-memory gradient Rosen projection method,
      which is applied to solve this optimization problem. The convergence analysis is
      given and simulations show that the proposed solution achieves significant
      throughput compared with existing approaches. 

PMID- 24883385
TI  - Parallel-batch scheduling and transportation coordination with waiting time
      constraint.
AB  - This paper addresses a parallel-batch scheduling problem that incorporates
      transportation of raw materials or semifinished products before processing with
      waiting time constraint. The orders located at the different suppliers are
      transported by some vehicles to a manufacturing facility for further processing.
      One vehicle can load only one order in one shipment. Each order arriving at the
      facility must be processed in the limited waiting time. The orders are processed
      in batches on a parallel-batch machine, where a batch contains several orders and
      the processing time of the batch is the largest processing time of the orders in
      it. The goal is to find a schedule to minimize the sum of the total flow time and
      the production cost. We prove that the general problem is NP-hard in the strong
      sense. We also demonstrate that the problem with equal processing times on the
      machine is NP-hard. Furthermore, a dynamic programming algorithm in
      pseudopolynomial time is provided to prove its ordinarily NP-hardness. An optimal
      algorithm in polynomial time is presented to solve a special case with equal
      processing times and equal transportation times for each order. 

PMID- 24883386
TI  - Improving vector evaluated particle swarm optimisation using multiple
      nondominated leaders.
AB  - The vector evaluated particle swarm optimisation (VEPSO) algorithm was previously
      improved by incorporating nondominated solutions for solving multiobjective
      optimisation problems. However, the obtained solutions did not converge close to
      the Pareto front and also did not distribute evenly over the Pareto front.
      Therefore, in this study, the concept of multiple nondominated leaders is
      incorporated to further improve the VEPSO algorithm. Hence, multiple nondominated
      solutions that are best at a respective objective function are used to guide
      particles in finding optimal solutions. The improved VEPSO is measured by the
      number of nondominated solutions found, generational distance, spread, and
      hypervolume. The results from the conducted experiments show that the proposed
      VEPSO significantly improved the existing VEPSO algorithms. 

PMID- 24883387
TI  - Multidimensional signal processing and applications.

PMID- 24883388
TI  - Towards a low-cost mobile subcutaneous vein detection solution using near
      infrared spectroscopy.
AB  - Excessive venipunctures are both time- and resource-consuming events, which cause
      anxiety, pain, and distress in patients, or can lead to severe harmful injuries.
      We propose a low-cost mobile health solution for subcutaneous vein detection
      using near-infrared spectroscopy, along with an assessment of the current state
      of the art in this field. The first objective of this study was to get a deeper
      overview of the research topic, through the initial team discussions and a
      detailed literature review (using both academic and grey literature). The second
      objective, that is, identifying the commercial systems employing near-infrared
      spectroscopy, was conducted using the PubMed database. The goal of the third
      objective was to identify and evaluate (using the IEEE Xplore database) the
      research efforts in the field of low-cost near-infrared imaging in general, as a
      basis for the conceptual model of the upcoming prototype. Although the reviewed
      commercial devices have demonstrated usefulness and value for peripheral veins
      visualization, other evaluated clinical outcomes are less conclusive. Previous
      studies regarding low-cost near-infrared systems demonstrated the general
      feasibility of developing cost-effective vein detection systems; however, their
      limitations are restricting their applicability to clinical practice. Finally,
      based on the current findings, we outline the future research direction. 

PMID- 24883389
TI  - Marker-assisted selection for recognizing wheat mutant genotypes carrying HMW
      glutenin alleles related to baking quality.
AB  - Allelic diversity of HMW glutenin loci in several studies revealed that allelic
      combinations affect dough quality. Dx5 + Dy10 subunits are related to good baking
      quality and Dx2 + Dy12 are related to undesirable baking quality. One of the most
      regular methods to evaluate the baking quality is SDS-PAGE which is used to
      improve baking quality labs. Marker-assisted selection is the method which can
      recognize the alleles related to baking quality and this method is based on
      polymerase chain reaction. 10 pairs of specific primers related to Dx2, Dx2.1,
      Dx5, Dy10, and Dy12 subunits were used for recognizing baking quality of some
      wheat varieties and some mutant genotypes. Only 5 pairs of them could show the
      specific bands. All subunits were recognized by the primers except Dx2.1. Some of
      the primers were extracted from previous studies and the others were designed
      based on D genome subunits of wheat. SDS-PAGE method accomplished having
      confidence in these marker's results. To realize the effect of mutation, seed
      storage proteins were measured. It showed that mutation had effect on the amount
      of seed storage protein on the mutant seeds (which showed polymorphism). 

PMID- 24883391
TI  - Improved ant algorithms for software testing cases generation.
AB  - Existing ant colony optimization (ACO) for software testing cases generation is a
      very popular domain in software testing engineering. However, the traditional ACO
      has flaws, as early search pheromone is relatively scarce, search efficiency is
      low, search model is too simple, positive feedback mechanism is easy to produce
      the phenomenon of stagnation and precocity. This paper introduces improved ACO
      for software testing cases generation: improved local pheromone update strategy
      for ant colony optimization, improved pheromone volatilization coefficient for
      ant colony optimization (IPVACO), and improved the global path pheromone update
      strategy for ant colony optimization (IGPACO). At last, we put forward a
      comprehensive improved ant colony optimization (ACIACO), which is based on all
      the above three methods. The proposed technique will be compared with random
      algorithm (RND) and genetic algorithm (GA) in terms of both efficiency and
      coverage. The results indicate that the improved method can effectively improve
      the search efficiency, restrain precocity, promote case coverage, and reduce the
      number of iterations.

PMID- 24883390
TI  - Benefits of repetitive transcranial magnetic stimulation (rTMS) for spastic
      subjects: clinical, functional, and biomechanical parameters for lower limb and
      walking in five hemiparetic patients.
AB  - Introduction. Spasticity is a disabling symptom resulting from reorganization of
      spinal reflexes no longer inhibited by supraspinal control. Several studies have
      demonstrated interest in repetitive transcranial magnetic stimulation in spastic
      patients. We conducted a prospective, randomized, double-blind crossover study on
      five spastic hemiparetic patients to determine whether this type of stimulation
      of the premotor cortex can provide a clinical benefit. Material and Methods. Two
      stimulation frequencies (1 Hz and 10 Hz) were tested versus placebo. Patients
      were assessed clinically, by quantitative analysis of walking and measurement of
      neuromechanical parameters (H and T reflexes, musculoarticular stiffness of the
      ankle). Results. No change was observed after placebo and 10 Hz protocols.
      Clinical parameters were not significantly modified after 1 Hz stimulation, apart
      from a tendency towards improved recruitment of antagonist muscles on the Fugl
      Meyer scale. Only cadence and recurvatum were significantly modified on
      quantitative analysis of walking. Neuromechanical parameters were modified with
      significant decreases in H max? /M max? and T/M max? ratios and stiffness indices
      9 days or 31 days after initiation of TMS. Conclusion. This preliminary study
      supports the efficacy of low-frequency TMS to reduce reflex excitability and
      stiffness of ankle plantar flexors, while clinical signs of spasticity were not
      significantly modified. 

PMID- 24883393
TI  - New type continuities via Abel convergence.
AB  - We investigate the concept of Abel continuity. A function f defined on a subset
      of R, the set of real numbers, is Abel continuous if it preserves Abel convergent
      sequences. Some other types of continuities are also studied and interesting
      result is obtained. It turned out that uniform limit of a sequence of Abel
      continuous functions is Abel continuous and the set of Abel continuous functions
      is a closed subset of continuous functions. 

PMID- 24883392
TI  - Risk intelligence: making profit from uncertainty in data processing system.
AB  - In extreme scale data processing systems, fault tolerance is an essential and
      indispensable part. Proactive fault tolerance scheme (such as the speculative
      execution in MapReduce framework) is introduced to dramatically improve the
      response time of job executions when the failure becomes a norm rather than an
      exception. Efficient proactive fault tolerance schemes require precise knowledge
      on the task executions, which has been an open challenge for decades. To well
      address the issue, in this paper we design and implement RiskI, a profile-based
      prediction algorithm in conjunction with a riskaware task assignment algorithm,
      to accelerate task executions, taking the uncertainty nature of tasks into
      account. Our design demonstrates that the nature uncertainty brings not only
      great challenges, but also new opportunities. With a careful design, we can
      benefit from such uncertainties. We implement the idea in Hadoop 0.21.0 systems
      and the experimental results show that, compared with the traditional LATE
      algorithm, the response time can be improved by 46% with the same system
      throughput. 

PMID- 24883394
TI  - Determination of coefficients of high-order schemes for Riemann-Liouville
      derivative.
AB  - Although there have existed some numerical algorithms for the fractional
      differential equations, developing high-order methods (i.e., with convergence
      order greater than or equal to 2) is just the beginning. Lubich has ever proposed
      the high-order schemes when he studied the fractional linear multistep methods,
      where he constructed the pth order schemes (p = 2, 3, 4, 5, 6) for the alphath
      order Riemann-Liouville integral and alphath order Riemann-Liouville derivative.
      In this paper, we study such a problem and develop recursion formulas to compute
      these coefficients in the higher-order schemes. The coefficients of higher-order
      schemes (p = 7,8, 9,10) are also obtained. We first find that these coefficients
      are oscillatory, which is similar to Runge's phenomenon. So, they are not
      suitable for numerical calculations. Finally, several numerical examples are
      implemented to testify the efficiency of the numerical schemes for p = 3,..., 6. 

PMID- 24883395
TI  - Flexural toughness of steel fiber reinforced high performance concrete containing
      nano-SiO2 and fly ash.
AB  - This paper aims to clarify the effect of steel fiber on the flexural toughness of
      the high performance concrete containing fly ash and nano-SiO2. The flexural
      toughness was evaluated by two methods, which are based on ASTM C1018 and DBV
      1998, respectively. By means of three-point bending method, the flexural
      toughness indices, variation coefficients of bearing capacity, deformation
      energy, and equivalent flexural strength of the specimen were measured,
      respectively, and the relational curves between the vertical load and the midspan
      deflection (P(V)-delta) were obtained. The results indicate that steel fiber has
      great effect on the flexural toughness parameters and relational curves (P(V)
      delta) of the three-point bending beam specimen. When the content of steel fiber
      increases from 0.5% to 2%, the flexural toughness parameters increase gradually
      and the curves are becoming plumper and plumper with the increase of steel fiber
      content, respectively. However these flexural toughness parameters begin to
      decrease and the curves become thinner and thinner after the steel fiber content
      exceeds 2%. It seems that the contribution of steel fiber to the improvement of
      flexural toughness of the high performance concrete containing fly ash and nano
      SiO2 is well performed only when the steel fiber content is less than 2%.

PMID- 24883396
TI  - Traveling wave solutions for epidemic cholera model with disease-related death.
AB  - Based on Codeco's cholera model (2001), an epidemic cholera model that
      incorporates the pathogen diffusion and disease-related death is proposed. The
      formula for minimal wave speed c (*) is given. To prove the existence of
      traveling wave solutions, an invariant cone is constructed by upper and lower
      solutions and Schauder's fixed point theorem is applied. The nonexistence of
      traveling wave solutions is proved by two-sided Laplace transform. However, to
      apply two-sided Laplace transform, the prior estimate of exponential decrease of
      traveling wave solutions is needed. For this aim, a new method is proposed, which
      can be applied to reaction-diffusion systems consisting of more than three
      equations. 

PMID- 24883398
TI  - Multiobjective resource-constrained project scheduling with a time-varying number
      of tasks.
AB  - In resource-constrained project scheduling (RCPS) problems, ongoing tasks are
      restricted to utilizing a fixed number of resources. This paper investigates a
      dynamic version of the RCPS problem where the number of tasks varies in time. Our
      previous work investigated a technique called mapping of task IDs for centroid
      based approach with random immigrants (McBAR) that was used to solve the dynamic
      problem. However, the solution-searching ability of McBAR was investigated over
      only a few instances of the dynamic problem. As a consequence, only a small
      number of characteristics of McBAR, under the dynamics of the RCPS problem, were
      found. Further, only a few techniques were compared to McBAR with respect to its
      solution-searching ability for solving the dynamic problem. In this paper, (a)
      the significance of the subalgorithms of McBAR is investigated by comparing McBAR
      to several other techniques; and (b) the scope of investigation in the previous
      work is extended. In particular, McBAR is compared to a technique called,
      Estimation Distribution Algorithm (EDA). As with McBAR, EDA is applied to solve
      the dynamic problem, an application that is unique in the literature. 

PMID- 24883397
TI  - Isolation and characterization of Paracoccus sp. GSM2 capable of degrading
      textile azo dye Reactive Violet 5.
AB  - A potential bacterial strain GSM2, capable of degrading an azo dye Reactive
      Violet 5 as a sole source of carbon, was isolated from textile mill effluent from
      Solapur, India. The 16S rDNA sequence and phenotypic characteristics indicated an
      isolated organism as Paracoccus sp. GSM2. This strain exhibited complete
      decolorization of Reactive Violet 5 (100 mg/L) within 16 h, while maximally it
      could decolorize 800 mg/L of dye within 38 h with 73% decolorization under static
      condition. For color removal, the most suitable pH and temperature were pH 6.0
      9.0 and 25-40  degrees C, respectively. The isolate was able to decolorize more
      than 70% of five structurally different azo dyes within 38 h. The isolate is salt
      tolerant as it can bring out more than 90% decolorization up to a salt
      concentration of 2% (w/v). UV-Visible absorption spectra before and after
      decolorization suggested that decolorization was due to biodegradation and was
      further confirmed by FT-IR spectroscopy. Overall results indicate the
      effectiveness of the strain GSM2 explored for the treatment of textile industry
      effluents containing various azo dyes. To our knowledge, this could be the first
      report on biodegradation of Reactive Violet 5 by Paracoccus sp. GSM2.

PMID- 24883399
TI  - Tissue fractions of cadmium in two hyperaccumulating Jerusalem artichoke
      genotypes.
AB  - In order to investigate the mechanisms in two Jerusalem artichoke (Helianthus
      tuberosus L.) genotypes that hyperaccumulate Cd, a sand-culture experiment was
      carried out to characterize fractionation of Cd in tissue of Cd-hyperaccumulating
      genotypes NY2 and NY5. The sequential extractants were: 80% v/v ethanol (FE),
      deionized water (FW), 1 M NaCl (FNaCl), 2% v/v acetic acid (FAcet), and 0.6 M HCl
      (FHCl). After 20 days of treatments, NY5 had greater plant biomass and greater Cd
      accumulation in tissues than NY2. In both genotypes the FNaCl fraction was the
      highest in roots and stems, whereas the FAcet and FHCl fractions were the highest
      in leaves. With an increase in Cd concentration in the culture solution, the
      content of every Cd fraction also increased. The FW and FNaCl ratios in roots
      were lower in NY5 than in NY2, while the amount of other Cd forms was higher. It
      implied that, in high accumulator, namely, NY5, the complex of insoluble
      phosphate tends to be shaped more easily which was much better for Cd
      accumulation. Besides, translocation from plasma to vacuole after combination
      with protein may be one of the main mechanisms in Cd-accumulator Jerusalem
      artichoke genotypes.

PMID- 24883402
TI  - A relationship: word alignment, phrase table, and translation quality.
AB  - In the last years, researchers conducted several studies to evaluate the machine
      translation quality based on the relationship between word alignments and phrase
      table. However, existing methods usually employ ad-hoc heuristics without
      theoretical support. So far, there is no discussion from the aspect of providing
      a formula to describe the relationship among word alignments, phrase table, and
      machine translation performance. In this paper, on one hand, we focus on
      formulating such a relationship for estimating the size of extracted phrase pairs
      given one or more word alignment points. On the other hand, a corpus-motivated
      pruning technique is proposed to prune the default large phrase table. Experiment
      proves that the deduced formula is feasible, which not only can be used to
      predict the size of the phrase table, but also can be a valuable reference for
      investigating the relationship between the translation performance and phrase
      tables based on different links of word alignment. The corpus-motivated pruning
      results show that nearly 98% of phrases can be reduced without any significant
      loss in translation quality. 

PMID- 24883403
TI  - Numerical manifold method for the forced vibration of thin plates during bending.
AB  - A novel numerical manifold method was derived from the cubic B-spline basis
      function. The new interpolation function is characterized by high-order
      coordination at the boundary of a manifold element. The linear elastic-dynamic
      equation used to solve the bending vibration of thin plates was derived according
      to the principle of minimum instantaneous potential energy. The method for the
      initialization of the dynamic equation and its solution process were provided.
      Moreover, the analysis showed that the calculated stiffness matrix exhibited
      favorable performance. Numerical results showed that the generalized degrees of
      freedom were significantly fewer and that the calculation accuracy was higher for
      the manifold method than for the conventional finite element method. 

PMID- 24883400
TI  - Leaf anatomy and photochemical behaviour of Solanum lycopersicum L. plants from
      seeds irradiated with low-LET ionising radiation.
AB  - Plants can be exposed to ionising radiation not only in Space but also on Earth,
      due to specific technological applications or after nuclear disasters. The
      response of plants to ionising radiation depends on radiation quality/quantity
      and/or plant characteristics. In this paper, we analyse some growth traits, leaf
      anatomy, and ecophysiological features of plants of Solanum lycopersicum L.
      "Microtom" grown from seeds irradiated with increasing doses of X-rays (0.3, 10,
      20, 50, and 100 Gy). Both juvenile and compound leaves from plants developed from
      irradiated and control seeds were analysed through light and epifluorescence
      microscopy. Digital image analysis allowed quantifying anatomical parameters to
      detect the occurrence of signs of structural damage. Fluorescence parameters and
      total photosynthetic pigment content were analysed to evaluate the functioning of
      the photosynthetic machinery. Radiation did not affect percentage and rate of
      seed germination. Plants from irradiated seeds accomplished the crop cycle and
      showed a more compact habitus. Dose-depended tendencies of variations occurred in
      phenolic content, while other leaf anatomical parameters did not show distinct
      trends after irradiation. The sporadic perturbations of leaf structure, observed
      during the vegetative phase, after high levels of radiation were not so severe as
      to induce any significant alterations in photosynthetic efficiency. 

PMID- 24883404
TI  - Balance maintenance in high-speed motion of humanoid robot arm-based on the 6D
      constraints of momentum change rate.
AB  - Based on the 6D constraints of momentum change rate (CMCR), this paper puts
      forward a real-time and full balance maintenance method for the humanoid robot
      during high-speed movement of its 7-DOF arm. First, the total momentum formula
      for the robot's two arms is given and the momentum change rate is defined by the
      time derivative of the total momentum. The author also illustrates the idea of
      full balance maintenance and analyzes the physical meaning of 6D CMCR and its
      fundamental relation to full balance maintenance. Moreover, discretization and
      optimization solution of CMCR has been provided with the motion constraint of the
      auxiliary arm's joint, and the solving algorithm is optimized. The simulation
      results have shown the validity and generality of the proposed method on the full
      balance maintenance in the 6 DOFs of the robot body under 6D CMCR. This method
      ensures 6D dynamics balance performance and increases abundant ZMP stability
      margin. The resulting motion of the auxiliary arm has large abundance in joint
      space, and the angular velocity and the angular acceleration of these joints lie
      within the predefined limits. The proposed algorithm also has good real-time
      performance. 

PMID- 24883405
TI  - Investigation of a new flux-modulated permanent magnet brushless motor for EVs.
AB  - This paper presents a flux-modulated direct drive (FMDD) motor. The key is to
      integrate the magnetic gear with the PM motor while removing the gear inner
      rotor. Hence, the proposed FMDD motor can achieve the low-speed high-torque
      output and high-speed compact design requirements as well as high-torque density
      with a simple structure. The output power equation is analytically derived. By
      using finite element analysis (FEA), the static characteristics of the proposed
      motor are obtained. Based on these characteristics, the system mathematical model
      can be established. Hence, the evaluation of system performances is conducted by
      computer simulation using the Matlab/Simulink. A prototype is designed and built
      for experimentation. Experimental results are given to verify the theoretical
      analysis and simulation. 

PMID- 24883406
TI  - Novel anode catalyst for direct methanol fuel cells.
AB  - PtRu catalyst is a promising anodic catalyst for direct methanol fuel cells
      (DMFCs) but the slow reaction kinetics reduce the performance of DMFCs.
      Therefore, this study attempts to improve the performance of PtRu catalysts by
      adding nickel (Ni) and iron (Fe). Multiwalled carbon nanotubes (MWCNTs) are used
      to increase the active area of the catalyst and to improve the catalyst
      performance. Electrochemical analysis techniques, such as energy dispersive X-ray
      spectrometry (EDX), X-ray diffraction (XRD), field emission scanning electron
      microscopy (FESEM), and X-ray photoelectron spectroscopy (XPS), are used to
      characterize the kinetic parameters of the hybrid catalyst. Cyclic voltammetry
      (CV) is used to investigate the effects of adding Fe and Ni to the catalyst on
      the reaction kinetics. Additionally, chronoamperometry (CA) tests were conducted
      to study the long-term performance of the catalyst for catalyzing the methanol
      oxidation reaction (MOR). The binding energies of the reactants and products are
      compared to determine the kinetics and potential surface energy for methanol
      oxidation. The FESEM analysis results indicate that well-dispersed nanoscale (2-5
      nm) PtRu particles are formed on the MWCNTs. Finally, PtRuFeNi/MWCNT improves the
      reaction kinetics of anode catalysts for DMFCs and obtains a mass current of 31 A
      g(-1) catalyst.

PMID- 24883407
TI  - A survey of noninteractive zero knowledge proof system and its applications.
AB  - Zero knowledge proof system which has received extensive attention since it was
      proposed is an important branch of cryptography and computational complexity
      theory. Thereinto, noninteractive zero knowledge proof system contains only one
      message sent by the prover to the verifier. It is widely used in the construction
      of various types of cryptographic protocols and cryptographic algorithms because
      of its good privacy, authentication, and lower interactive complexity. This paper
      reviews and analyzes the basic principles of noninteractive zero knowledge proof
      system, and summarizes the research progress achieved by noninteractive zero
      knowledge proof system on the following aspects: the definition and related
      models of noninteractive zero knowledge proof system, noninteractive zero
      knowledge proof system of NP problems, noninteractive statistical and perfect
      zero knowledge, the connection between noninteractive zero knowledge proof
      system, interactive zero knowledge proof system, and zap, and the specific
      applications of noninteractive zero knowledge proof system. This paper also
      points out the future research directions. 

PMID- 24883408
TI  - Synthesis and photophysical and electrochemical properties of functionalized mono
      , bis-, and trisanthracenyl bridged Ru(II) bis(2,2':6',2"-terpyridine) charge
      transfer complexes.
AB  - With the aim of developing new molecular devices having long-range electron
      transfer in artificial systems and as photosensitizers, a series of homoleptic
      ruthenium(II) bisterpyridine complexes bearing one to three anthracenyl units
      sandwiched between terpyridine and 2-methyl-2-butenoic acid group are synthesized
      and characterized. The complexes formulated as bis-4'-(9-monoanthracenyl-10-(2
      methyl-2-butenoic acid) terpyridyl) ruthenium(II) bis(hexafluorophosphate)
      (RBT1), bis-4'-(9-dianthracenyl-10-(2-methyl-2-butenoic acid) terpyridyl)
      ruthenium(II) bis(hexafluorophosphate) (RBT2), and bis-4'-(9-trianthracenyl-10-(2
      methyl-2-butenoic acid) terpyridyl) ruthenium(II) bis(hexafluorophosphate) (RBT3)
      were characterized by elemental analysis, FT-IR, UV-Vis, photoluminescence, (1)H
      and (13)C NMR spectroscopy, and electrochemical techniques by elemental analysis,
      FT-IR, UV-Vis, photoluminescence, (1)H and (13)C NMR spectroscopy, and
      electrochemical techniques. The cyclic voltammograms (CVs) of (RBT1), (RBT2), and
      (RBT3) display reversible one-electron oxidation processes at E 1/2 = 1.13 V,
      0.71 V, and 0.99 V, respectively (versus Ag/AgCl). Based on a general linear
      correlation between increase in the length of pi-conjugation bond and the molar
      extinction coefficients, the Ru(II) bisterpyridyl complexes show characteristic
      broad and intense metal-to-ligand charge transfer (MLCT) band absorption
      transitions between 480-600 nm, epsilon = 9.45 * 10(3) M(-1) cm(-1), and
      appreciable photoluminescence spanning the visible region.

PMID- 24883409
TI  - Using enhanced Russell model to solve inverse data envelopment analysis problems.
AB  - This paper studies the inverse data envelopment analysis using the nonradial
      enhanced Russell model. Necessary and sufficient conditions for inputs/outputs
      determination are introduced based on Pareto solutions of multiple-objective
      linear programming. In addition, an approach is investigated to identify extra
      input/lack output in each of input/output components (maximum/minimum
      reduction/increase amounts in each a of input/output components). In addition,
      the following question is addressed: if among a group of DMUs, it is required to
      increase inputs and outputs to a particular unit and assume that the DMU
      maintains its current efficiency level with respect to other DMUs, how much
      should the inputs and outputs of the DMU increase? This question is discussed as
      inverse data envelopment analysis problems, and a technique is suggested to
      answer this question. Necessary and sufficient conditions are established by
      employing Pareto solutions of multiple-objective linear programming as well. 

PMID- 24883410
TI  - Ductility and strength reduction factors for degrading structures considering
      cumulative damage.
AB  - The effect of cumulative damage on the strength requirements of degrading
      structures is assessed through the evaluation of the target ductility and
      corresponding strength reduction factors of simple degrading structures. While
      the reduction on ductility is established through the use of Park and Ang index,
      the suggestions given by Bojorquez and Rivera are used to model the degradation
      of the structural properties of the simple systems. Target ductilities and their
      corresponding reduced strength reduction factors are established for five sets of
      ground motions; most of them are recorded in California. The results given in
      this paper provide insight into all relevant parameters that should be considered
      during seismic design of earthquake-resistant structures. Finally, some
      recommendations to evaluate the effect of cumulative damage on seismic design are
      suggested. 

PMID- 24883411
TI  - The application of similar image retrieval in electronic commerce.
AB  - Traditional online shopping platform (OSP), which searches product information by
      keywords, faces three problems: indirect search mode, large search space, and
      inaccuracy in search results. For solving these problems, we discuss and research
      the application of similar image retrieval in electronic commerce. Aiming at
      improving the network customers' experience and providing merchants with the
      accuracy of advertising, we design a reasonable and extensive electronic commerce
      application system, which includes three subsystems: image search display
      subsystem, image search subsystem, and product information collecting subsystem.
      This system can provide seamless connection between information platform and OSP,
      on which consumers can automatically and directly search similar images according
      to the pictures from information platform. At the same time, it can be used to
      provide accuracy of internet marketing for enterprises. The experiment shows the
      efficiency of constructing the system.

PMID- 24883412
TI  - Novel MSVPWM to reduce the inductor current ripple for Z-source inverter in
      electric vehicle applications.
AB  - A novel modified space vector pulse width modulation (MSVPWM) strategy for Z
      Source inverter is presented. By rearranging the position of shoot-through
      states, the frequency of inductor current ripple is kept constant. Compared with
      existing MSVPWM strategies, the proposed approach can reduce the maximum inductor
      current ripple. So the volume of Z-source network inductor can be designed
      smaller, which brings the beneficial effect on the miniaturization of the
      electric vehicle controller. Theoretical findings in the novel MSVPWM for Z
      Source inverter have been verified by experiment results. 

PMID- 24883414
TI  - Hybrid particle swarm optimization for hybrid flowshop scheduling problem with
      maintenance activities.
AB  - A hybrid algorithm which combines particle swarm optimization (PSO) and iterated
      local search (ILS) is proposed for solving the hybrid flowshop scheduling (HFS)
      problem with preventive maintenance (PM) activities. In the proposed algorithm,
      different crossover operators and mutation operators are investigated. In
      addition, an efficient multiple insert mutation operator is developed for
      enhancing the searching ability of the algorithm. Furthermore, an ILS-based local
      search procedure is embedded in the algorithm to improve the exploitation ability
      of the proposed algorithm. The detailed experimental parameter for the canonical
      PSO is tuning. The proposed algorithm is tested on the variation of 77 Carlier
      and Neron's benchmark problems. Detailed comparisons with the present efficient
      algorithms, including hGA, ILS, PSO, and IG, verify the efficiency and
      effectiveness of the proposed algorithm. 

PMID- 24883413
TI  - Physicochemical properties and surfaces morphologies evaluation of MTA FillApex
      and AH plus.
AB  - The solubility, pH, electrical conductivity, and radiopacity of AH Plus and MTA
      FillApex were evaluated. In addition, the surfaces morphologies of the sealers
      were analyzed by using scanning electron microscopy. For pH test, the samples
      were immersed in distilled water at different periods of time. The same solution
      was used for electrical conductivity measurement. The solubility and radiopacity
      were evaluated according to ANSI/ADA. Statistical analyses were carried out at 5%
      level of significance. MTA FillApex presented higher mean value for solubility
      and electrical conductivity. No significant difference was observed in the mean
      values for pH reading. AH Plus presented higher radiopacity mean values. MTA
      FillApex presented an external surface with porosities and a wide range of sizes.
      In conclusion, the materials fulfill the ANSI/ADA requirements when considering
      the radiopacity and solubility. AH Plus revealed a compact and homogeneous
      surface with more regular aspects and equal particle sizes. 

PMID- 24883415
TI  - The role of mandibular third molars on lower anterior teeth crowding and relapse
      after orthodontic treatment: a systematic review.
AB  - AIMS: To evaluate the role of third molars in the development of crowding or
      relapse after orthodontic treatment in the anterior segment of the dental arch.
      METHODS: PubMed search of the literature was performed selecting all the articles
      relevant to the topic and limiting the studies to controlled trials on humans and
      written in English language. Systematic review was conducted according to the
      PRISMA (preferred reporting items for systematic reviews and meta-analyses)
      statement. RESULTS: A total of 12 clinical studies were included in the review. A
      high risk of bias was found in most of the articles, either because the relative
      items assessed were inadequate or because they were unclearly described. The
      third molars were not correlated with more severe anterior tooth crowding in most
      of the studies. However, four of them described a different outcome. CONCLUSION:
      Definitive conclusions on the role of the third molars in the development of
      anterior tooth crowding cannot be drawn. A high risk of bias was found in most of
      the trials, and the outcomes were not consistent. However, most of the studies do
      not support a cause-and-effect relationship; therefore, third molar extraction to
      prevent anterior tooth crowding or postorthodontic relapse is not justified.

PMID- 24883416
TI  - Multiscale distance coherence vector algorithm for content-based image retrieval.
AB  - Multiscale distance coherence vector algorithm for content-based image retrieval
      (CBIR) is proposed due to the same descriptor with different shapes and the
      shortcomings of antinoise performance of the distance coherence vector algorithm.
      By this algorithm, the image contour curve is evolved by Gaussian function first,
      and then the distance coherence vector is, respectively, extracted from the
      contour of the original image and evolved images. Multiscale distance coherence
      vector was obtained by reasonable weight distribution of the distance coherence
      vectors of evolved images contour. This algorithm not only is invariable to
      translation, rotation, and scaling transformation but also has good performance
      of antinoise. The experiment results show us that the algorithm has a higher
      recall rate and precision rate for the retrieval of images polluted by noise. 

PMID- 24883417
TI  - Analytic approximate solution for Falkner-Skan equation.
AB  - This paper deals with the Falkner-Skan nonlinear differential equation. An
      analytic approximate technique, namely, optimal homotopy asymptotic method
      (OHAM), is employed to propose a procedure to solve a boundary-layer problem. Our
      method does not depend upon small parameters and provides us with a convenient
      way to optimally control the convergence of the approximate solutions. The
      obtained results reveal that this procedure is very effective, simple, and
      accurate. A very good agreement was found between our approximate results and
      numerical solutions, which prove that OHAM is very efficient in practice,
      ensuring a very rapid convergence after only one iteration. 

PMID- 24883418
TI  - A hybrid multiuser detector based on MMSE and AFSA for TDRS system forward link.
AB  - This study mainly focuses on multiuser detection in tracking and data relay
      satellite (TDRS) system forward link. Minimum mean square error (MMSE) is a low
      complexity multiuser detection method, but MMSE detector cannot achieve
      satisfactory bit error ratio and near-far resistance, whereas artificial fish
      swarm algorithm (AFSA) is expert in optimization and it can realize the global
      convergence efficiently. Therefore, a hybrid multiuser detector based on MMSE and
      AFSA (MMSE-AFSA) is proposed in this paper. The result of MMSE and its modified
      formations are used as the initial values of artificial fishes to accelerate the
      speed of global convergence and reduce the iteration times for AFSA. The
      simulation results show that the bit error ratio and near-far resistance
      performances of the proposed detector are much better, compared with MF, DEC, and
      MMSE, and are quite close to OMD. Furthermore, the proposed MMSE-AFSA detector
      also has a large system capacity. 

PMID- 24883419
TI  - Improving causality induction with category learning.
AB  - Causal relations are of fundamental importance for human perception and
      reasoning. According to the nature of causality, causality has explicit and
      implicit forms. In the case of explicit form, causal-effect relations exist at
      either clausal or discourse levels. The implicit causal-effect relations heavily
      rely on empirical analysis and evidence accumulation. This paper proposes a
      comprehensive causality extraction system (CL-CIS) integrated with the means of
      category-learning. CL-CIS considers cause-effect relations in both explicit and
      implicit forms and especially practices the relation between category and
      causality in computation. In elaborately designed experiments, CL-CIS is
      evaluated together with general causality analysis system (GCAS) and general
      causality analysis system with learning (GCAS-L), and it testified to its own
      capability and performance in construction of cause-effect relations. This paper
      confirms the expectation that the precision and coverage of causality induction
      can be remarkably improved by means of causal and category learning. 

PMID- 24883420
TI  - Seismic behavior and force-displacement characterization of neotype column-slab
      high piers.
AB  - The seismic behavior and plasticity spreading of a neotype column-slab high pier
      are researched in this paper. Four scale model tests of a web slab with two
      boundary columns are carried out under cyclic inelastic lateral displacements
      simulating seismic response. The test results show that the neotype column-slab
      high pier has strong and stable bearing capacity, good ductility, and energy
      dissipation capacity. The experimental values pertaining to the spread of
      plasticity are derived. An approach for deriving the spread of plasticity
      analytically is deduced and applied to the four tests. This method accurately
      assesses a pier's spread of plasticity for most ductility levels. At nearly all
      ductility levels, the mean difference between analytical assessments of the
      spread of plasticity and results from 4 large-scale tests is 12% with a 9%
      coefficient of variation. 

PMID- 24883422
TI  - Human body 3D posture estimation using significant points and two cameras.
AB  - This paper proposes a three-dimensional (3D) human posture estimation system that
      locates 3D significant body points based on 2D body contours extracted from two
      cameras without using any depth sensors. The 3D significant body points that are
      located by this system include the head, the center of the body, the tips of the
      feet, the tips of the hands, the elbows, and the knees. First, a linear support
      vector machine- (SVM-) based segmentation method is proposed to distinguish the
      human body from the background in red, green, and blue (RGB) color space. The SVM
      based segmentation method uses not only normalized color differences but also
      included angle between pixels in the current frame and the background in order to
      reduce shadow influence. After segmentation, 2D significant points in each of the
      two extracted images are located. A significant point volume matching (SPVM)
      method is then proposed to reconstruct the 3D significant body point locations by
      using 2D posture estimation results. Experimental results show that the proposed
      SVM-based segmentation method shows better performance than other gray level- and
      RGB-based segmentation approaches. This paper also shows the effectiveness of the
      3D posture estimation results in different postures. 

PMID- 24883421
TI  - Transmission electron microscopic morphological study and flow cytometric
      viability assessment of Acinetobacter baumannii susceptible to Musca domestica
      cecropin.
AB  - Multidrug-resistant (MDR) Acinetobacter baumannii infections are difficult to
      treat owing to the extremely limited armamentarium. Expectations about
      antimicrobial peptides' use as new powerful antibacterial agents have been raised
      on the basis of their unique mechanism of action. Musca domestica cecropin (Mdc),
      a novel antimicrobial peptide from the larvae of Housefly (Musca domestica), has
      potently active against Gram-positive and Gram-negative bacteria standard strain.
      Here we evaluated the antibacterial activity of Mdc against clinical isolates of
      MDR-A. baumannii and elucidate the related antibacterial mechanisms. The minimal
      inhibitory concentration (MIC) of Mdc was 4 MUg/mL. Bactericidal kinetics of Mdc
      revealed rapid killing of A. baumannii (30 min). Flow cytometry using viability
      stain demonstrated that Mdc causes A. baumannii membrane permeabilization in a
      concentration- and time-dependent process, which correlates with the bactericidal
      action. Moreover, transmission electron microscopic (TEM) examination showed that
      Mdc is capable of disrupting the membrane of bacterial cells, resulting in efflux
      of essential cytoplasmic components. Overall, Mdc could be a promising
      antibacterial agent for MDR-A. baumannii infections.

PMID- 24883423
TI  - The impact of nanosilver addition on element ions release form light-cured dental
      composite and compomer into 0.9% NaCl.
AB  - The aim of this paper was to identify and to assess in semi-quantified way the
      release of different ions from composite and compomer restorative materials
      subjected to 0.9% NaCl solution, which simulates the environment of the human
      body. In the present study, the number of ions (Al, Ag, Ba, Sr, Ti) released from
      dental fillings over time (one week, one month and 3 months), in different
      temperatures (23 degrees C, 37 degrees C) and depending on the materials applied
      (unmodified/modified with nanosilver) was investigated. The results suggest that
      nanosilver addition influences directly on the process of metal ion releasing
      into 0.9% NaCl solution. The increase in the number of counts of metal ions was
      observed in the solutions in which samples modified with nanosilver were kept.
      Higher amount of metal ion release was observed for composite samples rather than
      for compomer materials. The study revealed that in general the number of released
      metal ions increases with the time of storage (for metal ions: Ti, Ba, Sr) and at
      higher temperature (Ag, Ti, Ba). Reverse tendency observed for silver ion release
      versus incubation time may be caused by the process of silver adsorption, which
      takes place on the surface of analyzed material and test-tube walls, where
      samples were incubated. 

PMID- 24883429
TI  - Novel DFO-functionalized mesoporous silica for iron sensing. Part 2. Experimental
      detection of free iron concentration (pFe) in urine samples.
AB  - Successful in vivo chelation treatment of iron(iii) overload pathologies requires
      that a significant fraction of the administered drug actually chelates the toxic
      metal. Increased mobilization of the iron(iii) in experiments on animals or
      humans, most often evaluated from urinary output, is usually used as an
      assessment tool for chelation therapy. Alternatively, the efficiency of a drug is
      estimated by calculating the complexing ability of a chelating agent towards
      Fe(iii). The latter is calculated by the pFe value, defined as the negative
      logarithm of the concentration of the free metal ion in a solution containing 10
      MUM total ligand and 1 MUM total metal at a physiological pH of 7.4. In theory,
      pFe has to be calculated taking into account all the complexation equilibria
      involving the metal and the possible ligands. Nevertheless, complexation
      reactions in complex systems such as serum and urine may hardly be accurately
      modelled by computer software. The experimental determination of the bioavailable
      fraction of iron(iii) in biological fluids would therefore be of the utmost
      relevance in the clinical practice. The efficiency of the therapy could be more
      easily estimated as well as the course of overload pathologies. In this context,
      the aim of the present work was the development of a sensor to assess the free
      iron directly in biological fluids (urine) of patients under treatment with
      chelating agents. In the proposed device (DFO-MS), the strong iron chelator
      deferoxamine (DFO) is immobilized on the MCM-41 mesoporous silica. The
      characterization of the iron(iii) sorption on DFO-MS was undertaken, firstly in
      0.1 M KNO3, then directly in urine samples, in order to identify the sorption
      mechanism. The stoichiometry of the reaction in the solid phase was found to be:
      with an exchange constant (average value) of log betaex = 40(1). The application
      of DFO-MS to assess pFe in SPU (Simulating Pathology Urine) samples was also
      considered. The results obtained were very promising for a future validation and
      subsequent application of the sensor in samples of patients undergoing chelation
      therapy.

PMID- 24883431
TI  - Graphene as an atomically thin barrier to Cu diffusion into Si.
AB  - The evolution of copper-based interconnects requires the realization of an
      ultrathin diffusion barrier layer between the Cu interconnect and insulating
      layers. The present work reports the use of atomically thin layer graphene as a
      diffusion barrier to Cu metallization. The diffusion barrier performance is
      investigated by varying the grain size and thickness of the graphene layer;
      single-layer graphene of average grain size 2 +/- 1 MUm (denoted small-grain
      SLG), single-layer graphene of average grain size 10 +/- 2 MUm (denoted large
      grain SLG), and multi-layer graphene (MLG) of thickness 5-10 nm. The thermal
      stability of these barriers is investigated after annealing Cu/small-grain
      SLG/Si, Cu/large-grain SLG/Si, and Cu/MLG/Si stacks at different temperatures
      ranging from 500 to 900  degrees C. X-ray diffraction, transmission electron
      microscopy, and time-of-flight secondary ion mass spectroscopy analyses confirm
      that the small-grain SLG barrier is stable after annealing up to 700  degrees C
      and that the large-grain SLG and MLG barriers are stable after annealing at 900 
      degrees C for 30 min under a mixed Ar and H2 gas atmosphere. The time-dependent
      dielectric breakdown (TDDB) test is used to evaluate graphene as a Cu diffusion
      barrier under real device operating conditions, revealing that both large-grain
      SLG and MLG have excellent barrier performance, while small-grain SLG fails
      quickly. Notably, the large-grain SLG acts as a better diffusion barrier than the
      thicker MLG in the TDDB test, indicating that the grain boundary density of a
      graphene diffusion barrier is more important than its thickness. The near-zero
      thickness SLG serves as a promising Cu diffusion barrier for advanced
      metallization. 

PMID- 24883430
TI  - Bioactive oligosaccharide natural products.
AB  - Covering up to December 2013. Oligosaccharide natural products target a wide
      spectrum of biological processes including disruption of cell wall biosynthesis,
      interference of bacterial translation, and inhibition of human alpha-amylase.
      Correspondingly, oligosaccharides possess the potential for development as
      treatments of such diverse diseases as bacterial infections and type II diabetes.
      Despite their potent and selective activities and potential clinical relevance,
      isolated bioactive secondary metabolic oligosaccharides are less prevalent than
      other classes of natural products and their biosynthesis has received
      comparatively less attention. This review highlights the unique modes of action
      and biosynthesis of four classes of bioactive oligosaccharides: the
      orthosomycins, moenomycins, saccharomicins, and acarviostatins.

PMID- 24883432
TI  - Spatial organization of Pseudomonas aeruginosa biofilms probed by combined matrix
      assisted laser desorption ionization mass spectrometry and confocal Raman
      microscopy.
AB  - Bacteria growing as surface attached biofilms differ significantly from
      planktonic cells in several important traits that are reflected in the
      spatiotemporal organization of the cells and the extracellular polymeric
      substances they secrete. The structural and chemical features that define these
      biofilms are explored here using a combination of matrix-assisted laser
      desorption ionization mass spectrometry (MALDI MS) and confocal Raman
      microspectroscopies (CRM) to characterize and compare the composition and
      distribution of biomolecules found in biofilms and planktonic cells of the
      bacterium Pseudomonas aeruginosa. Three-day old P. aeruginosa biofilms show
      dramatic differences in molecular composition compared to planktonic cultures.
      CRM reveals that wild-type planktonic cell Raman spectra are characterized by
      bands linked to cellular constituents and are dominated by contributions from DNA
      and RNA-related bands. In contrast, biofilm spectra are dominated by bands
      characteristic of glycolipids - rhamnolipids - polysaccharides and by secreted
      proteins. LDI MS was applied in turn to identify the rhamnolipids present in the
      biofilm. Experiments were also conducted using an acyl homoserine lactone quorum
      sensing-deficient mutant (DeltalasIDeltarhlI), which is incapable of producing
      rhamnolipids. CRM and LDI MS analyses revealed that while molecular composition
      of the planktonic quorum sensing-deficient cells is similar to that of the wild
      type planktonic cells, several compositional differences are observed in the
      mutant after biofilm growth, including complete absence of detectable
      rhamnolipids. CRM vibrational spectra of the mutant cells are very similar for
      planktonic and biofilm growth conditions, indicating that biofilm formation is
      greatly hindered in the absence of functioning quorum sensing machinery. 

PMID- 24883434
TI  - Determinants, reproducibility, and seasonal variation of ergosterol  levels in
      house dust.
AB  - This study aimed to clarify the determinants that affect the concentrations of
      ergosterol and viable fungi in house dust and to examine the seasonal variation
      and reproducibility of ergosterol concentrations indoors. In studying the
      determinants, dust samples from living room floors and vacuum cleaner dust bags
      were collected from 107 farming and 105 non-farming homes. Ergosterol levels were
      determined with gas chromatography-mass spectrometry,and the dust bag dust was
      cultivated for enumeration of fungal genera. Lifestyle and environmental factors,
      for example using of the fireplace, and visible mold observations in homes,
      explained 20-26% of the variation of fungal concentrations. For the
      reproducibility study, samples were collected from five urban homes in four
      different seasons. The reproducibility of ergosterol determinations within a
      sample was excellent (ICC = 89.8) for floor dust and moderate (ICC = 63.8) for
      dust bag dust, but poor when sampling the same home throughout a year (ICC = 31.3
      and 12.6, respectively) due to large temporal variation in ergosterol
      concentrations. In conclusion, environmental characteristics only partially
      predicted the variation of fungal concentrations. Based on these studies, we
      recommend repeated sampling of dust over time if one seeks to adequately describe
      overall fungal levels and exposure in a home. PRACTICAL IMPLICATIONS: This study
      shows that levels of ergosterol and viable fungi in house dust are related to
      visible mold observations. Only 20% of the variation in fungal levels can be
      explained with questionnaires, and therefore, environmental samples need to be
      taken in addition. Reproducibility of ergosterol determination was excellent for
      floor dust, and thus, ergosterol measurements from floor dust samples could be
      suitable for assessing the fungal load in building investigations. The temporal
      variation needs to be taken into account when describing the ergosterol
      concentration of urban homes.

PMID- 24883435
TI  - A laboratory study for assessing speech privacy in a simulated  open-plan office.
AB  - The aim of this study is to assess speech privacy in open-plan office using two
      recently introduced single-number quantities: the spatial decay rate of speech,
      DL(2,S) [dB], and the A-weighted sound pressure level of speech at a distance of
      4 m, L(p,A,S,4) m [dB]. Open-plan offices were modeled using a DL(2,S) of 4, 8,
      and 12 dB, and L(p,A,S,4) m was changed in three steps, from 43 to 57 dB.Auditory
      experiments were conducted at three locations with source-receiver distances of
      8, 16, and 24 m, while background noise level was fixed at 30 dBA.A total of 20
      subjects were asked to rate the speech intelligibility and listening difficulty
      of 240 Korean sentences in such surroundings. The speech intelligibility scores
      were not affected by DL(2,S) or L(p,A,S,4) m at a source-receiver distance of 8
      m; however, listening difficulty ratings were significantly changed with
      increasing DL(2,S) and L(p,A,S,4) m values. At other locations, the influences of
      DL(2,S) and L(p,A,S,4) m on speech intelligibility and listening difficulty
      ratings were significant. It was also found that the speech intelligibility
      scores and listening difficulty ratings were considerably changed with increasing
      the distraction distance (r(D)). Furthermore, listening difficulty is more
      sensitive to variations in DL(2,S) and L(p,A,S,4) m than intelligibility scores
      for sound fields with high speech transmission performances. PRACTICAL
      IMPLICATIONS: The recently introduced single-number quantities in the ISO
      standard, based on the spatial distribution of sound pressure level, were
      associated with speech privacy in an open-plan office. The results support single
      number quantities being suitable to assess speech privacy, mainly at large
      distances. This new information can be considered when designing open-plan
      offices and making acoustic guidelines of open-plan offices.

PMID- 24883433
TI  - Next-generation DNA sequencing reveals that low fungal diversity  in house dust
      is associated with childhood asthma development.
AB  - Dampness and visible mold in homes are associated with asthma development, but
      causal mechanisms remain unclear. The goal of this research was to explore
      associations among measured dampness, fungal exposure, and childhood asthma
      development without the bias of culture-based microbial analysis. In the low
      income, Latino CHAMACOS birth cohort, house dust was collected at age 12 months,
      and asthma status was determined at age 7 years.The current analysis included 13
      asthma cases and 28 controls. Next-generation DNA sequencing methods quantified
      fungal taxa and diversity. Lower fungal diversity (number of fungal operational
      taxonomic units) was significantly associated with increased risk of asthma
      development: unadjusted odds ratio(OR) 4.80 (95% confidence interval (CI) 1.04
      22.1). Control for potential confounders strengthened this relationship.
      Decreased diversity within the genus Cryptococcus was significantly associated
      with increased asthma risk (OR 21.0, 95% CI 2.16-204). No fungal taxon (species,
      genus, class) was significantly positively associated with asthma development,
      and one was significantly negatively associated. Elevated moisture was associated
      with increased fungal diversity, and moisture/mold indicators were associated
      with four fungal taxa. Next-generation DNA sequencing provided comprehensive
      estimates of fungal identity and diversity, demonstrating significant
      associations between low fungal diversity and childhood asthma development in
      this community. PRACTICAL IMPLICATIONS: Early life exposure to low fungal
      diversity in house dust was associated with increased risk for later asthma
      developmen tin this low-income, immigrant community. No individual fungal taxon
      (species, genus, or class) was associated with asthma development, although
      exposure to low diversity within the genus Cryptococcus was associated with
      asthma development. Future asthma development studies should incorporate fungal
      diversity measurements, in addition to measuring individual fungal taxa. These
      results represent a step toward identifying the aspect(s) of indoor microbial
      populations that are associated with asthma development and suggest that
      understanding the factors that control diversity in the indoor environment may
      lead to public health recommendations for asthma prevention in the future.

PMID- 24883437
TI  - IGF2: an endocrine hormone to improve islet transplant survival.
AB  - In the week following pancreatic islet transplantation, up to 50% of transplanted
      islets are lost due to apoptotic cell death triggered by hypoxic and pro
      inflammatory cytokine-mediated cell stress. Thus, therapeutic approaches designed
      to protect islet cells from apoptosis could significantly improve islet
      transplant success. IGF2 is an anti-apoptotic endocrine protein that inhibits
      apoptotic cell death through the mitochondrial (intrinsic pathway) or via
      antagonising activation of pro-inflammatory cytokine signalling (extrinsic
      pathway), in doing so IGF2 has emerged as a promising therapeutic molecule to
      improve islet survival in the immediate post-transplant period. The development
      of novel biomaterials coated with IGF2 is a promising strategy to achieve this.
      This review examines the mechanisms mediating islet cell apoptosis in the peri-
      and post-transplant period and aims to identify the utility of IGF2 to promote
      islet survival and enhance long-term insulin independence rates within the
      setting of clinical islet transplantation.

PMID- 24883436
TI  - The identification and developmental requirements of colonic CD169+ macrophages.
AB  - CD169-positive macrophages in the marginal zone of the spleen and subcapsular
      sinus of lymph nodes play an important role as gatekeepers, strategically located
      to capture pathogens. Here we identified a population of CD169-positive
      macrophages in the colon and investigated which factors influenced their
      development. Murine colonic CD115+ F4/80(lo) CD11c(lo) macrophages expressing
      CD169 were present in the lamina propria, mainly surrounding the crypts. In spite
      of the high levels of bacterial flora in the colon and the importance of Toll
      like receptor signalling in mucosal homeostasis, the presence of CD169+
      macrophages was not affected in mice that were deficient in MyD88-mediated Toll
      like receptor signalling and in mice in which the bacterial flora was eradicated.
      Whereas the development of splenic CD169+ macrophages was dependent on
      lymphotoxin alpha, colonic CD169+ macrophages were present in normal numbers in
      lymphotoxin alpha-deficient mice. In contrast, reduced numbers of CD169+
      macrophages were found in the colon of mice deficient in vitamin A, whereas
      CD169+ macrophages in the spleen were unaffected. In conclusion, we identified a
      new macrophage subset in the lamina propria of the colon characterized by the
      expression of CD169. Its differentiation, unlike CD169+ macrophages in lymphoid
      organs, is independent of lymphotoxin alpha signalling, but requires vitamin A.

PMID- 24883438
TI  - [The reward system of the brain: the brain loves surprises].

PMID- 24883439
TI  - Milestone in pacemaker history: first postapproval implantation of NanostimTM in
      UK.

PMID- 24883441
TI  - High-density lipoproteins may offer a more  promising route to statin therapy.

PMID- 24883440
TI  - Riociguat recommended by CHMP for approval in the EU for use in two forms of
      pulmonary hypertension.

PMID- 24883442
TI  - PROGNOSIS looking good for a possible serum  test for preeclampsia.

PMID- 24883443
TI  - Clinical effect of E-series of prostaglandin receptor 2 and epidermal growth
      factor receptor signal pathways in the development of esophageal squamous cell
      carcinoma.
AB  - Signal pathways mediated by epidermal growth factor receptor (EGFR) and E-series
      of prostaglandin receptors (EPs) are closely correlated to the pathogenesis of
      tumor. This experiment was designed to investigate the expression and clinical
      significance of EP2 and EGFR in esophageal squamous cell carcinoma (ESCC). Tissue
      samples were collected reterospectively from 87 patients with ESCC (first
      diagnosed). The patients were followed up for 5 years after radical surgery. The
      expression of EP-2 and EGFR were examined by tissue chip technology and
      immunohistochemistry methods. Clinicopathological and prognostic impact were
      evaluated. Overexpression of EGFR and EP-2 was more observed in ESCC than the
      control group (58.6% vs. 13.9%; 52.9% vs. 4.88%, P < 0.001, respectively); which
      correlated with tumor infiltration depth, lymph node metastasis, and tumor-lymph
      node-metastasis staging. Both the EP-2 and EGFR overexpression were detected in
      39 specimens and exhibited the positive correlation (P < 0.001, r = 0.404).
      Overexpression of EP2 and EGFR exhibited significant correlation with worse 5
      year overall survival than those with negative result (17.6% vs. 27.8%, P =
      0.011; 10.9% vs. 34.1%, P < 0.001, respectively). Cox proportional hazard model
      showed that the T-staging, lymph node metastasis, and EGFR overexpression were
      the independent risk factors of the prognosis. The present study exhibited that
      the overexpression of EP2 and EGFR in ESCC tissues might play an important role
      in carcinogenesis and the progression of ESCC.

PMID- 24883444
TI  - [Physician assistant studies" - a new career option].

PMID- 24883445
TI  - Five-year clinical outcome and patency rate of device-dependent venous grafts
      after clampless OPCAB with PAS-port automated proximal anastomosis: the PAPA
      Study.
AB  - OBJECTIVE: To evaluate long-term clinical performance and angiographic patency of
      automated proximal venous anastomoses following clampless coronary artery bypass
      (C-CAB). METHODS: Observational study in patients submitted for isolated C-CAB
      and at least one proximal aortosaphenous anastomosis performed with an automated
      connector (Cardica PAS-Port) including 152 consecutive patients (165 devices and
      199 device-dependent distal anastomoses), with LVEF > 30% and saphenous vein
      diameter of 4-6 mm. Clinical follow-up was 96% complete (4101/4269 pt-months).
      Graft patency rate was assessed with 64-slice CT-scan or coronary angiography.
      Freedom from major adverse cardiac and cerebrovascular events (MACCE) was
      reported as actuarial probability with 95% confidence limits and venous graft
      patency as actual rate at every year interval. RESULTS: Early operative mortality
      was 1.9%; incidence of neurologic injury was zero. Freedom from MACCE was 92.7 +/
      2.1 at one year and 85.2 +/- 4.8 at five years. The actual patency rate of
      device-dependent venous grafts was 90%, 85%, 84%, 84%, and 93% for one-, two-,
      three-, four-, and five-year-old grafts, respectively. CONCLUSIONS: The device is
      a well-performing system for proximal anastomoses. The incidence of neurologic
      complications seems to be reduced with this clampless approach. The high patency
      rate is stable over time.

PMID- 24883446
TI  - Aggressive bone marrow metastatic medullary thyroid carcinoma.

PMID- 24883447
TI  - Transvenous atrial pacing from the superior vena cava stump after the hemi-fontan
      operation--a new approach.
AB  - BACKGROUND: The placement of a standard endocardial pacemaker system is
      challenging after a superior cavopulmonary connection (hemi-Fontan operation or
      Glenn shunt) as the continuity between the superior vena cava (SVC) and right
      atrium is divided. The standard transvenous approach for endocardial lead
      placement has therefore in general been avoided, and epicardial leads have been
      placed. METHODS: In three patients after a hemi-Fontan procedure, we found viable
      atrial tissue in the SVC stump of the superior cavopulmonary anastomosis, which
      was still connected electrically to the right atrium into which active-fixation
      leads could be safely implanted. RESULTS: There was excellent short- and long
      term atrial pacing and sensing characteristics in the SVC stump. CONCLUSIONS: We
      describe a technique for transvenous pacing in patients after the hemi-Fontan
      procedure using the conventional subclavian vein approach and pectoral placement
      of the generator. For ventricular pacing, it was possible to cross the patch
      dividing the right atrium from the SVC either using a spontaneous leak or by
      needle puncture.

PMID- 24883448
TI  - Pacing and implantable cardioverter defibrillator lead perforation as assessed by
      multiplanar reformatted ECG-gated cardiac computed tomography and clinical
      correlates.
AB  - INTRODUCTION: We aimed to assess the utility of cardiac computed tomography (CT)
      in the evaluation of right atrial (RA) and right ventricular (RV) pacemaker and
      implantable cardiac defibrillator lead perforation. METHODS: Images from a 320
      slice electrocardiogram-gated cardiac CT scanner were retrospectively
      independently analyzed by two reviewers for lead position, pericardial effusion,
      and perforation.Perforation results were correlated with pacing sensing,
      impedance, and threshold measurements. RESULTS: A total of 52 patients had RV
      leads and 35 had RA leads. Five of 17 RV apical, one of 35 RV nonapical, and none
      of the 35 RA leads perforated through the myocardium on CT imaging criteria. Two
      "clinically" perforated leads (that had protruded 5 mm and 15 mm from the outer
      edge of the myocardium)had pericardial effusions and changes in pacing
      parameters, and required RV lead repositioning. In contrast,there were four
      apparent "radiologic" perforations (that had protruded only an average 1.5+/-0.5
      mm from the outer edge of the myocardium) that did not require repositioning.
      These had the radiologic appearance of perforation on cardiac CT; however, they
      were not associated with pericardial effusions or significant changes in RV
      pacing lead sensing, impedance, and threshold measurements. CONCLUSIONS: Cardiac
      CT scanning with multiplanar reformatting is useful for documenting lead position
      and assessing for possible cardiac perforation. The clinical significance and
      natural history of leads with only the appearance of perforation on cardiac CT is
      uncertain.

PMID- 24883449
TI  - Prolonged ablation on critical segments of pulmonary vein ostia in paroxysmal
      atrial fibrillation: a prospective randomized controlled study.
AB  - INTRODUCTION: Electrical reconnection of the pulmonary veins (PVs) plays a key
      role in the recurrence of atrial fibrillation (AF) after ablative treatment. This
      randomized controlled study tested the hypothesis that prolonged ablations, on
      areas that may be critical for left atrial (LA)-PV conduction, can significantly
      reduce the rate of acute PV reconnection and AF recurrence. METHODS: Patients
      with paroxysmal AF were randomly assigned to either a control or an add-on
      group.Ostial PV isolation (PVI) was performed by point-to-point RF ablation
      (irrigated tip, 30 Watts, 30 seconds).An ostial segment was assumed to be
      critical for LA-PV connection if any of the following reactions occurred during
      RF application: (1) sudden delay of LA-PV conduction, (2) change of activation
      sequence,and (3) PVI. In this case, RF application was prolonged from 30 seconds
      to 90 seconds in the add-on group only. RESULTS: A total of 131 patients (58 +/-
      11 years, 47 female) were assigned to a control (n = 64) and an add-on (n = 67)
      group. Ablation time was longer in the add-on (48 +/- 16 minutes vs 37 +/- 15
      minutes, P = 0.03). Acute PV reconnection was observed in 20 of 64 controls and
      in eight of 66 add-on patients (31% vs 12%, P < 0.001). During a follow-up of 26
      months, AF recurred in 33 of 64 controls and in 16 of 66 add-on patients (52% vs
      24%, P = 0.001) after a single ablation procedure. CONCLUSIONS: Prolonged
      radiofrequency application on critical segments of LA-PV connection is a safe and
      effective ablative strategy that significantly reduces acute PV reconnection and
      AF recurrence rates after a single ablation procedure for paroxysmal AF.

PMID- 24883450
TI  - Review of reviews 2014: a virtual issue.

PMID- 24883451
TI  - Grid cells in an inhibitory network.

PMID- 24883452
TI  - Astrocytes go awry in Huntington's disease.

PMID- 24883453
TI  - Turning heads to remember places.

PMID- 24883454
TI  - Large orbital magnetic moment in Pt13 clusters.
AB  - We present an extensive study of Pt13 clusters embedded in a Na-Y zeolite, by
      comparing calculations for isolated clusters to experimental data. We perform
      structural refinements for various geometries involving the isolated clusters and
      calculate the corresponding x-ray absorption and magnetic circular dichroism
      spectra, from the joint perspective of pseudopotential plane wave calculations
      and real space multiple scattering theory. Taking into account the spin-orbit
      coupling significantly improves the previous scalar relativistic predictions of
      magnetic properties. The ensemble of embedded Pt13 is found to be dominated by a
      non-magnetic cuboctahedral geometry. One of the implications is that the ground
      state of Pt13 clusters in the zeolite environment is different from that of
      isolated particles. We investigate several isomers that yield a magnetic
      signature. Furthermore, their abundance was estimated by direct comparison with
      experiment. We found that one third of the magnetic moment of Pt13 comes from the
      orbital contribution, in agreement with the experimental value. We therefore
      provide theoretical proof of the extraordinary orbital magnetization in Pt13
      clusters.

PMID- 24883455
TI  - Loss of phasic dopamine: a new addiction marker?

PMID- 24883457
TI  - Diagnosis and management of shock in the emergency department.
AB  - Shock is a state of acute circulatory failure leading to decreased organ
      perfusion, with inadequate delivery of oxygenated blood to tissues and resultant
      end-organ dysfunction. The mechanisms that can result in shock are divided into 4
      categories: (1) hypovolemic, (2) distributive, (3) cardiogenic, and (4)
      obstructive. While much is known regarding treatment of patients in shock,
      several controversies continue in the literature. Assessment begins with
      identifying the need for critical interventions such as intubation, mechanical
      ventilation, or obtaining vascular access. Prompt workup should be initiated with
      laboratory testing (especially of serum lactate levels) and imaging, as
      indicated. Determining the intravascular volume status of patients in shock is
      critical and aids in categorizing and informing treatment decisions. This issue
      reviews the 4 primary categories of shock as well as special categories,
      including shock in pregnancy, traumatic shock, septic shock, and cardiogenic
      shock in myocardial infarction. Adherence to evidence-based care of the specific
      causes of shock can optimize a patient's chances of surviving this life
      threatening condition.

PMID- 24883456
TI  - Inge Grundke-Iqbal, Ph.D. (1937-2012): the discoverer of the abnormal
      hyperphosphorylation of tau in Alzheimer's disease.

PMID- 24883458
TI  - Emergency department management of calcium-channel blocker, beta blocker, and
      digoxin toxicity.
AB  - While it is relatively uncommon, an overdose of calcium-channel blockers, beta
      blockers, or digoxin has a significant morbidity and mortality rate, and its
      management can be complex. Digoxin toxicity can present with an acute overdose or
      as chronic toxicity while a patient is on therapeutic dosing, which has
      implications for diagnosis and management. While the patient's specific clinical
      presentation may depend on factors such as the time of exposure and the type of
      agent ingested, the differential diagnosis of the bradycardic and hypotensive
      patient is narrow, and toxicity from these agents must be considered. This review
      provides an evidence-based overview of the emergency department management of
      calcium-channel blocker overdose, beta blocker overdose, and digoxin toxicity.

PMID- 24883906
TI  - Partnering with families.
AB  - 1.The numbers of ethnic minority persons in the United States are increasing
      faster than Caucasian populations. This means that nurse will be caring for an
      increasingly diverse patient pool. 2. Ethnic differences have been discovered to
      play a role in the efficacy of psychoactive medication. These differences result
      from a number of biological as well as non-biological factors. 3. Nurses have a
      professional obligation to be aware and sensitive to differential responses to
      treatment.

PMID- 24883914
TI  - Nanowires grown on InP (100): growth directions, facets, crystal structures, and
      relative yield control.
AB  - Growth of III-V nanowires on the [100]-oriented industry standard substrates is
      critical for future integrated nanowire device development. Here we present an in
      depth analysis of the seemingly complex ensembles of epitaxial nanowires grown on
      InP (100) substrates. The nanowires are categorized into three types as vertical,
      nonvertical, and planar, and the growth directions, facets, and crystal structure
      of each type are investigated. The nonvertical growth directions are
      mathematically modeled using a three-dimensional multiple-order twinning concept.
      The nonvertical nanowires can be further classified into two different types,
      with one type growing in the ?111? directions and the other in the ?100?
      directions after initial multiple three-dimensional twinning. We find that 99% of
      the total nanowires are grown either along ?100?, ?111?, or ?110? growth
      directions by {100} or {111} growth facets. We also demonstrate relative control
      of yield of these different types of nanowires, by tuning pregrowth annealing
      conditions and growth parameters. Together, the knowledge and controllability of
      the types of nanowires provide an ideal foundation to explore novel geometries
      that combine different crystal structures, with potential for both fundamental
      science research and device applications. 

PMID- 24883916
TI  - Blurring the lines between ribosomal and nonribosomal peptide scaffolds.
AB  - Two of the canons of protein science have been (1) that there are 20-22 amino
      acids that are proteinogenic and (2), with the exception of achiral glycine, that
      the other residues are L-amino acids. By contrast, the presence of
      nonproteinogenic amino acid residues and D-enantiomers has been regarded as
      hallmarks of nonribosomal peptides. The recent discoveries that bottromycins and
      polytheonamides, containing beta-methyl and D-amino acid residues, are of
      ribosomal origin blur the distinctions between peptide structures derivable by
      ribosomal and nonribosomal assembly lines and reveal new chemistry for
      posttranslational maturation of proteins.

PMID- 24883930
TI  - Electrochemical control over photoinduced electron transfer and trapping in CdSe
      CdTe quantum-dot solids.
AB  - Understanding and controlling charge transfer between different kinds of
      colloidal quantum dots (QDs) is important for devices such as light-emitting
      diodes and solar cells and for thermoelectric applications. Here we study
      photoinduced electron transfer between CdTe and CdSe QDs in a QD film. We find
      that very efficient electron trapping in CdTe QDs obstructs electron transfer to
      CdSe QDs under most conditions. Only the use of thiol ligands results in somewhat
      slower electron trapping; in this case the competition between trapping and
      electron transfer results in a small fraction of electrons being transferred to
      CdSe. However, we demonstrate that electron trapping can be controlled and even
      avoided altogether by using the unique combination of electrochemistry and
      transient absorption spectroscopy. When the Fermi level is raised
      electrochemically, traps are filled with electrons and electron transfer from
      CdTe to CdSe QDs occurs with unity efficiency. These results show the great
      importance of knowing and controlling the Fermi level in QD films and open up the
      possibility of studying the density of trap states in QD films as well as the
      systematic investigation of the intrinsic electron transfer rates in donor
      acceptor films. 

PMID- 24883952
TI  - Enhanced photoactivity with nanocluster-grafted titanium dioxide photocatalysts.
AB  - Titanium dioxide (TiO2), as an excellent photocatalyst, has been intensively
      investigated and widely used in environmental purification. However, the wide
      band gap of TiO2 and rapid recombination of photogenerated charge carriers
      significantly limit its overall photocatalytic efficiency. Here, efficient
      visible-light-active photocatalysts were developed on the basis of TiO2 modified
      with two ubiquitous nanoclusters. In this photocatalytic system, amorphous Ti(IV)
      oxide nanoclusters were demonstrated to act as hole-trapping centers on the
      surface of TiO2 to efficiently oxidize organic contaminants, while amorphous
      Fe(III) or Cu(II) oxide nanoclusters mediate the reduction of oxygen molecules.
      Ti(IV) and Fe(III) nanoclusters-modified TiO2 exhibited the highest quantum
      efficiency (QE = 92.2%) and reaction rate (0.69 MUmol/h) for 2-propanol
      decomposition among previously reported photocatalysts, even under visible-light
      irradiation (420-530 nm). The desirable properties of efficient photocatalytic
      performance with high stability under visible light with safe and ubiquitous
      elements composition enable these catalysts feasible for large-scale practical
      applications. 

PMID- 24883933
TI  - Fluorinated proteins: from design and synthesis to structure and stability.
AB  - Fluorine is all but absent from biology; however, it has proved to be a
      remarkably useful element with which to modulate the activity of biological
      molecules and to study their mechanism of action. Our laboratory's interest in
      incorporating fluorine into proteins was stimulated by the unusual
      physicochemical properties exhibited by perfluorinated small molecules. These
      include extreme chemical inertness and thermal stability, properties that have
      made them valuable as nonstick coatings and fire retardants. Fluorocarbons also
      exhibit an unusual propensity to phase segregation. This phenomenon, which has
      been termed the "fluorous effect", has been effectively exploited in organic
      synthesis to purify compounds from reaction mixtures by extracting fluorocarbon
      tagged molecules into fluorocarbon solvents. As biochemists, we were curious to
      explore whether the unusual physicochemical properties of perfluorocarbons could
      be engineered into proteins. To do this, we developed a synthesis of a highly
      fluorinated amino acid, hexafluoroleucine, and designed a model 4-helix bundle
      protein, alpha4H, in which the hydrophobic core was packed exclusively with
      leucine. We then investigated the effects of repacking the hydrophobic core of
      alpha4H with various combinations of leucine and hexafluoroleucine. These initial
      studies demonstrated that fluorination is a general and effective strategy for
      enhancing the stability of proteins against chemical and thermal denaturation and
      proteolytic degradation. We had originally envisaged that the "fluorous
      interactions", postulated from the self-segregating properties of fluorous
      solvents, might be used to mediate specific protein-protein interactions
      orthogonal to those of natural proteins. However, various lines of evidence
      indicate that no special, favorable fluorine-fluorine interactions occur in the
      core of the fluorinated alpha4 protein. This makes it unlikely that fluorinated
      amino acids can be used to direct protein-protein interactions. More recent
      detailed thermodynamic and structural studies in our laboratory have uncovered
      the basis for the remarkably general ability of fluorinated side chains to
      stabilize protein structure. Crystal structures of alpha4H and its fluorinated
      analogues show that the fluorinated residues fit into the hydrophobic core with
      remarkably little perturbation to the structure. This is explained by the fact
      that fluorinated side chains, although larger, very closely preserve the shape of
      the hydrophobic amino acids they replace. Thus, an increase in buried hydrophobic
      surface area in the folded state is responsible for the additional thermodynamic
      stability of the fluorinated protein. Measurements of DeltaG degrees , DeltaH
      degrees , DeltaS degrees , and DeltaCp degrees  for unfolding demonstrate that
      the "fluorous" stabilization of these protein arises from the hydrophobic effect
      in the same way that hydrophobic partitioning stabilizes natural proteins.

PMID- 24883956
TI  - Some practical approaches to treating electrostatic polarization of proteins.
AB  - Conspectus Electrostatic interaction plays a significant role in determining many
      properties of biomolecules, which exist and function in aqueous solution, a
      highly polar environment. For example, proteins are composed of amino acids with
      charged, polar, and nonpolar side chains and their specific electrostatic
      properties are fundamental to the structure and function of proteins. An
      important issue that arises in computational study of biomolecular interaction
      and dynamics based on classical force field is lack of polarization. Polarization
      is a phenomenon in which the charge distribution of an isolated molecule will be
      distorted when interacting with another molecule or presented in an external
      electric field. The distortion of charge distribution is intended to lower the
      overall energy of the molecular system, which is counter balanced by the
      increased internal energy of individual molecules due to the distorted charge
      distributions. The amount of the charge redistribution, which characterizes the
      polarizability of a molecule, is determined by the level of the charge
      distortion. Polarization is inherently quantum mechanical, and therefore
      classical force fields with fixed atomic charges are incapable of capturing this
      important effect. As a result, simulation studies based on popular force fields,
      AMBER, CHARMM, etc., lack the polarization effect, which is a widely known
      deficiency in most computational studies of biomolecules today. Many efforts have
      been devoted to remedy this deficiency, such as adding additional movable charge
      on the atom, allowing atomic charges to fluctuate, or including induced
      multipoles. Although various successes have been achieved and progress at various
      levels has been reported over the past decades, the issue of lacking polarization
      in force field based simulations is far from over. For example, some of these
      methods do not always give converged results, and other methods require huge
      computational cost. This Account reviews recent work on developing polarized and
      polarizable force fields based on fragment quantum mechanical calculations for
      proteins. The methods described here are based on quantum mechanical calculations
      of proteins in solution, but with a different level of rigor and different
      computational efficiency for the molecular dynamics applications. In the general
      approach, a fragment quantum mechanical calculation for protein with implicit
      solvation is carried out to derive a polarized protein-specific charge (PPC) for
      any given protein structure. The PPC correctly reflects the polarization state of
      the protein in a given conformation, and it can also be dynamically changed as
      the protein changes conformation in dynamics simulations. Another approach that
      is computationally more efficient is the effective polarizable bond method in
      which only polar bonds or groups can be polarized and their polarizabilities are
      predetermined from quantum mechanical calculations of these groups in external
      electric fields. Both methods can be employed for applications in various
      situations by taking advantage of their unique features. 

PMID- 24883981
TI  - Chiral colloids: homogeneous suspension of individualized SiO2 helical and
      twisted nanoribbons.
AB  - Finely tuned chiral nanometric silica fibers were synthesized based on sol-gel
      chemistry using organic self-assembly as a template. The optimization of the sol
      gel process in acidic conditions allowed us to reduce the transcription time by a
      factor of 10. These nanohelices were successfully fragmented while preserving the
      fine internal structures from several micrometers to several hundreds of
      nanometers in length by a sonication method previously reported for carbon
      nanotubes. By carefully choosing the nature of the solvent, the sonication power,
      pH in the case of water, and densification of the silica walls by freeze-drying,
      the homogeneous and stable colloidal suspensions of individualized chiral
      nanometric silica ribbons with controlled length were obtained. 

PMID- 24883986
TI  - Aiming for benchmark accuracy with the many-body expansion.
AB  - Conspectus The past 15 years have witnessed an explosion of activity in the field
      of fragment-based quantum chemistry, whereby ab initio electronic structure
      calculations are performed on very large systems by decomposing them into a large
      number of relatively small subsystem calculations and then reassembling the
      subsystem data in order to approximate supersystem properties. Most of these
      methods are based, at some level, on the so-called many-body (or "n-body")
      expansion, which ultimately requires calculations on monomers, dimers, ..., n
      mers of fragments. To the extent that a low-order n-body expansion can reproduce
      supersystem properties, such methods replace an intractable supersystem
      calculation with a large number of easily distributable subsystem calculations.
      This holds great promise for performing, for example, "gold standard" CCSD(T)
      calculations on large molecules, clusters, and condensed-phase systems. The
      literature is awash in a litany of fragment-based methods, each with their own
      working equations and terminology, which presents a formidable language barrier
      to the uninitiated reader. We have sought to unify these methods under a common
      formalism, by means of a generalized many-body expansion that provides a
      universal energy formula encompassing not only traditional n-body cluster
      expansions but also methods designed for macromolecules, in which the supersystem
      is decomposed into overlapping fragments. This formalism allows various fragment
      based methods to be systematically classified, primarily according to how the
      fragments are constructed and how higher-order n-body interactions are
      approximated. This classification furthermore suggests systematic ways to improve
      the accuracy. Whereas n-body approaches have been thoroughly tested at low levels
      of theory in small noncovalent clusters, we have begun to explore the efficacy of
      these methods for large systems, with the goal of reproducing benchmark-quality
      calculations, ideally meaning complete-basis CCSD(T). For high accuracy, it is
      necessary to deal with basis-set superposition error, and this necessitates the
      use of many-body counterpoise corrections and electrostatic embedding methods
      that are stable in large basis sets. Tests on small noncovalent clusters suggest
      that total energies of complete-basis CCSD(T) quality can indeed be obtained,
      with dramatic reductions in aggregate computing time. On the other hand, naive
      applications of low-order n-body expansions may benefit from significant error
      cancellation, wherein basis-set superposition error partially offsets the effects
      of higher-order n-body terms, affording fortuitously good results in some cases.
      Basis sets that afford reasonable results in small clusters behave erratically in
      larger systems and when high-order n-body expansions are employed. For large
      systems, and (H2O)N?30 is large enough, the combinatorial nature of the many-body
      expansion presents the possibility of serious loss-of-precision problems that are
      not widely appreciated. Tight thresholds are required in the subsystem
      calculations in order to stave off size-dependent errors, and high-order
      expansions may be inherently numerically ill-posed. Moreover, commonplace script-
      or driver-based implementations of the n-body expansion may be especially
      susceptible to loss-of-precision problems in large systems. These results suggest
      that the many-body expansion is not yet ready to be treated as a "black-box"
      quantum chemistry method. 

PMID- 24884001
TI  - Optical properties of metal-molybdenum disulfide hybrid nanosheets and their
      application for enhanced photocatalytic hydrogen evolution.
AB  - Limited control over charge recombination between photogenerated charge carriers
      largely hinders the progress in photocatalysis. Here, we introduce metal
      nanoparticles (Cr, Ag) to the surface of MoS2 nanosheets by simple synthetic
      means creating a hybrid metal-MoS2 nanosheet system with well-defined
      metal/semiconductor interfaces. We demonstrate that this hybrid nanosheet
      structure is capable of decoupling light absorption, primarily in MoS2, and
      carrier separation, across the metal-MoS2 heterostructure leading to drastic
      quenching of recombination between photogenerated carriers in MoS2, as proven by
      absorptance, photoluminescence, and ultrafast pump-probe spectroscopy. The
      photocatalytic activity in the hybrid system is also improved, which further
      shows excellent stability against photocorrosion. 

PMID- 24884003
TI  - Toward reversible control of cucurbit[n]uril complexes.
AB  - CONSPECTUS: The cucurbit[n]uril (CBn) host family consists of a group of rigid
      macrocyclic hosts with barrel-like shapes and limited solubility in aqueous
      media. These hosts are capable of reaching high binding affinities with
      positively charged hydrophobic guests. In optimum cases, equilibrium association
      constant (K) values as high as 10(17) M(-1) have been reported, exceeding the
      binding affinity of the avidin-biotin host-guest pair. The synthetic CBn
      receptors have shattered the notion that highly stable noncovalent complexes can
      form only when one of the partners is a molecule of biological origin. The work
      described in this Account is concerned with the development of methods geared
      toward the reversible modulation of the binding affinity of CBn inclusion
      complexes under mild conditions. A good fraction of the research work has dealt
      with redox active guests, such as 4,4'-bipyridinium (viologen), ferrocene, and
      cobaltocenium derivatives. Our experimental results show that the thermodynamics
      and kinetics of the electron transfer reactions of these compounds can be
      substantially altered by complexation with CBn hosts, and therefore, electron
      transfer reactions can be used to exert a measure of control on the overall
      binding affinity of the CBn complexes. We have also developed systems in which
      proton transfer reactions have a strong effect on the binding affinity. With more
      structurally elaborate guests containing more than one adjacent binding sites,
      proton transfer reactions may affect the average location of the CBn host within
      the complexes. A series of guest compounds containing paramagnetic 2,2,6,6
      tetramethylpiperidine-1-oxyl (TEMPO) residues also exhibit interesting binding
      properties with CB7 and CB8. The latter host forms a very stable host-guest pair
      with TEMPO subunits, in which the nitroxide group resides inside the host cavity.
      Finally, with suitable ditopic guests, we have detected distinct microscopic
      complexes using experimental techniques with relatively slow time scales, such as
      NMR spectroscopy. These unusual findings are the result of the considerable
      thermodynamic and kinetic stability of CBn inclusion complexes.

PMID- 24884013
TI  - Heterogeneously integrated silicon photonics for the mid-infrared and
      spectroscopic sensing.
AB  - Besides being the foundational material for microelectronics, crystalline silicon
      has long been used for the production of infrared lenses and mirrors. More
      recently, silicon has become the key material to achieve large-scale integration
      of photonic devices for on-chip optical interconnect and signal processing. For
      optics, silicon has significant advantages: it offers a very high refractive
      index and is highly transparent in the spectral range from 1.2 to 8 MUm. To fully
      exploit silicon's superior performance in a remarkably broad range and to enable
      new optoelectronic functionalities, here we describe a general method to
      integrate silicon photonic devices on arbitrary foreign substrates. In
      particular, we apply the technique to integrate silicon microring resonators on
      mid-infrared compatible substrates for operation in the mid-infrared. These high
      performance mid-infrared optical resonators are utilized to demonstrate, for the
      first time, on-chip cavity-enhanced mid-infrared spectroscopic analysis of
      organic chemicals with a limit of detection of less than 0.1 ng.

PMID- 24884020
TI  - Mental health promotion & protection.
AB  - 1. Public Health Nurses (PHNs) provide many mental health pro-motion and
      protection services within the scope of their daily practice. 2. The nursing
      story provides nurses with an opportunity to describe nursing care. 3. The
      American culture places enormous pressure on immigrants to change their life
      practices, including those related to health.

PMID- 24884035
TI  - Achieving high-quality single-atom nitrogen doping of graphene/SiC(0001) by ion
      implantation and subsequent thermal stabilization.
AB  - We report a straightforward method to produce high-quality nitrogen-doped
      graphene on SiC(0001) using direct nitrogen ion implantation and subsequent
      stabilization at temperatures above 1300 K. We demonstrate that double defects,
      which comprise two nitrogen defects in a second-nearest-neighbor (meta)
      configuration, can be formed in a controlled way by adjusting the duration of
      bombardment. Two types of atomic contrast of single N defects are identified in
      scanning tunneling microscopy. We attribute the origin of these two contrasts to
      different tip structures by means of STM simulations. The characteristic dip
      observed over N defects is explained in terms of the destructive quantum
      interference.

PMID- 24884022
TI  - DNA materials: bridging nanotechnology and biotechnology.
AB  - CONSPECTUS: In recent decades, DNA has taken on an assortment of diverse roles,
      not only as the central genetic molecule in biological systems but also as a
      generic material for nanoscale engineering. DNA possesses many exceptional
      properties, including its biological function, biocompatibility, molecular
      recognition ability, and nanoscale controllability. Taking advantage of these
      unique attributes, a variety of DNA materials have been created with properties
      derived both from the biological functions and from the structural
      characteristics of DNA molecules. These novel DNA materials provide a natural
      bridge between nanotechnology and biotechnology, leading to far-ranging real
      world applications. In this Account, we describe our work on the design and
      construction of DNA materials. Based on the role of DNA in the construction, we
      categorize DNA materials into two classes: substrate and linker. As a substrate,
      DNA interfaces with enzymes in biochemical reactions, making use of molecular
      biology's "enzymatic toolkit". For example, employing DNA as a substrate, we
      utilized enzymatic ligation to prepare the first bulk hydrogel made entirely of
      DNA. Using this DNA hydrogel as a structural scaffold, we created a protein
      producing DNA hydrogel via linking plasmid DNA onto the hydrogel matrix through
      enzymatic ligation. Furthermore, to fully make use of the advantages of both DNA
      materials and polymerase chain reaction (PCR), we prepared thermostable branched
      DNA that could remain intact even under denaturing conditions, allowing for their
      use as modular primers for PCR. Moreover, via enzymatic polymerization, we have
      recently constructed a physical DNA hydrogel with unique internal structure and
      mechanical properties. As a linker, we have used DNA to interface with other
      functional moieties, including gold nanoparticles, clay minerals, proteins, and
      lipids, allowing for hybrid materials with unique properties for desired
      applications. For example, we recently designed a DNA-protein conjugate as a
      universal adapter for protein detection. We further demonstrate a diverse
      assortment of applications for these DNA materials including diagnostics, protein
      production, controlled drug release systems, the exploration of life evolution,
      and plasmonics. Although DNA has shown great potential as both substrate and
      linker in the construction of DNA materials, it is still in the initial stages of
      becoming a well-established and widely used material. Important challenges
      include the ease of design and fabrication, scaling-up, and minimizing cost. We
      envision that DNA materials will continue to bridge the gap between
      nanotechnology and biotechnology and will ultimately be employed for many real
      world applications.

PMID- 24884043
TI  - Lithium, inositol and mitochondria.
AB  - Our recent DNA-microarray and proteomics studies searching for pathways affected
      both by chronic lithium treatment and by knockout of each of two genes (IMPA1 or
      Slc5a3) encoding for proteins related to inositol metabolism, indicated up
      regulation of mitochondria-related genes and autophagy-related proteins in the
      frontal cortex. Differently from previously reported observations of aberrant
      mitochondrial function in bipolar patients which leave a causality relationship
      between mitochondrial dysfunction and bipolar disorder an open question, the
      behavioral results of our recent report following rotenone treatment tempt us to
      speculate that mitochondrial dysfunction predisposes manic behavior and that
      drugs targeted to ameliorate mitochondrial function are potential preventers of
      bursting manic episodes. However, the promiscuity of the involvement of
      mitochondrial dysfunction and impaired autophagy in the pathophysiology of
      psychiatric and neurodegenerative disorders raises questions regarding the
      credibility and relevance of these findings.

PMID- 24884059
TI  - Two-dimensional molybdenum tungsten diselenide alloys: photoluminescence, Raman
      scattering, and electrical transport.
AB  - Two-dimensional transition-metal dichalcogenide alloys have attracted intense
      attention due to their tunable band gaps. In the present work, photoluminescence,
      Raman scattering, and electrical transport properties of monolayer and few-layer
      molybdenum tungsten diselenide alloys (Mo1-xWxSe2, 0 <= x <= 1) are
      systematically investigated. The strong photoluminescence emissions from Mo1
      xWxSe2 monolayers indicate composition-tunable direct band gaps (from 1.56 to
      1.65 eV), while weak and broad emissions from the bilayers indicate indirect band
      gaps. The first-order Raman modes are assigned by polarized Raman spectroscopy.
      Second-order Raman modes are assigned according to its frequencies. As
      composition changes in Mo1-xWxSe2 monolayers and few layers, the out-of-plane A1g
      mode showed one-mode behavior, while B2g(1) (only observed in few layers), in
      plane E2g(1), and all observed second-order Raman modes showed two-mode
      behaviors. Electrical transport measurement revealed n-type semiconducting
      transport behavior with a high on/off ratio (>10(5)) for Mo1-xWxSe2 monolayers. 

PMID- 24884073
TI  - A heart-felt remembrance: a ritual to help participants grieve the loss of
      another member in their cardiac rehabilitation program.
AB  - 1. Attending to the cardiac participant's grief following a death of another
      member is important to their cardiac health, as well as assisting them to enhance
      their connection to the program. 2.Using a grief ritual in an up-beat, wellness
      type setting is effective and appreciated by participants. It also demonstrates a
      commitment to mind-body healing. 3. Utilizing guidelines, such as suggested in
      this article, in creating and practicing your ritual is necessary to help focus
      the staff and the participants, so that the major concentration then is eliciting
      members'thoughts and feelings.

PMID- 24884074
TI  - Cooperative assembly of pyrene-functionalized donor/acceptor blend for ordered
      nanomorphology by intermolecular noncovalent pi-pi interactions.
AB  - A facile approach to develop the stable and well-defined bulk heterojunction
      (BHJ) nanomorphology has been demonstrated. Novel pyrene (Py)-functionalized
      diblock copolymers poly(3-hexylthiophene)-block-poly[3-(10-(pyren-1
      yloxy)decyloxy)thiophene] (P3HT-b-P3TPy), and pyrene-functionalized fullerene
      [6,6]-phenyl-C61-butyric acid 1-pyrene butyl ester (PCBPy), were successfully
      synthesized. The pi-pi interactions of Py mesogens interdigitated between the
      functionalized fullerene and P3TPy segment can allow for the cooperative assembly
      of P3HT-b-P3TPy and PCBPy. The orientation of the Py mesogens also can further
      enhance the molecular arrangement. Compared with the as-cast and thermal
      annealing, solvent annealing can promote cooperative assembly of P3HT-b
      P3TPy:PCBPy undergoing the slow film growth. Note that the assembly
      microstructure strongly depends on the molar ratio of P3HT and P3TPy with Py
      mesogens. Low loading of P3TPy block in the copolymers blends keeps the same
      behavior to the P3HT, whereas relatively high loading of Py mesogens favors the
      better intermolecular pi-pi stacking interactions between P3HT-b-P3TPy and PCBPy.
      As a result, the P3HT-b-P3TPy(3/1) forms the orientated nanowires with PCBPy in
      bulk heterojunction, and the average domain size is estimated to be 10-20 nm,
      which is desirable for enlarge surface area for donor/acceptor interfaces and
      give a bicontinuous pathway for efficient electron transfer. Furthermore, the
      cooperative assembly between P3HT-b-P3TPy and PCBPy is found to effectively
      suppress the PCBPy macrophase separation, and stabilize the blend morphology. 

PMID- 24884080
TI  - Enhanced photoelectrochemical activity of a hierarchical-ordered TiO2 mesocrystal
      and its sensing application on a carbon nanohorn support scaffold.
AB  - A ternary hybrid was developed through interaction between a hierarchical-ordered
      TiO2 and a thiol group that was obtained by in situ chemical polymerization of L
      cysteine on the carbon nanohorn (CNH) superstructure modified electrode. Herein,
      unique-ordered TiO2 superstructures with quasi-octahedral shape that possess high
      crystallinity, high porosity, oriented subunit alignment, very large specific
      surface area, and superior photocatalytic activity were first introduced as a
      photosensitizer element in the photoelectrochemical determination. Additionally,
      the assembly of hierarchical-structured CNHs was used to provide an excellent
      electron-transport matrix to capture and transport an electron from excited
      anatase to the electrode rapidly, hampering the electron-hole recombination
      effectively, resulting in improved photoelectrochemical response and higher
      photocatalytic activity in the visible light region. Owing to the dependence of
      the photocurrent signal on the concentration of electron donor, 4-methylimidozal,
      which can act as a photogenerated hole scavenger, an exquisite
      photoelectrochemical sensor was successfully fabricated with a wide linear range
      from 1 * 10(-4) to 1 * 10(-10) M, and the detection limit was down to 30 pM. The
      low applied potential of 0.2 V was beneficial to the elimination of interference
      from other reductive species that coexisted in the real samples. More
      importantly, the mesocrystal was first introduced in the fabricating of a
      biosensor, which not only opens up a new avenue for biosensors manufactured based
      on mesocrystal materials but also provides beneficial lessons in the research
      fields ranging from solar cells to photocatalysis.

PMID- 24884092
TI  - Solid-phase synthesis of trisubstituted 2,5-dihydrobenzo[f][1,2,5]thiadiazepine
      1,1-dioxide derivatives.
AB  - The solid-phase synthesis of trisubstituted 2,5
      dihydrobenzo[f][1,2,5]thiadiazepine 1,1-dioxides is reported. Acyclic polymer
      supported intermediates were prepared using commercially available building
      blocks: Fmoc-protected amino acids, 2-nitrobenzenesulfonyl chlorides, and
      bromoketones. The acyclic precursors underwent acid-mediated release from the
      resin and the cyclization was completed in solution. 

PMID- 24884097
TI  - Using therapeutic support: my hands-on experience as a psychiatric nurse.
AB  - 1. Therapeutic support is an indispensable tool in clinical nursing,regardless of
      specialty area. 2. Nurses are being increasingly recognized as more effective
      therapists who bring broader perspective because of being caregivers for the
      client's physical needs. 3. Nurses, especially those who work in psychiatric
      units, require more than what basic nursing programs currently provide in
      psychiatric nursing education.

PMID- 24884098
TI  - Electrochemistry and spectroelectrochemistry of 1,4-dinitrobenzene in
      acetonitrile and room-temperature ionic liquids: ion-pairing effects in mixed
      solvents.
AB  - Room-temperature ionic liquids (RTILs) have been shown to have a significant
      effect on the redox potentials of compounds such as 1,4-dinitrobenzene (DNB),
      which can be reduced in two one-electron steps. The most noticeable effect is
      that the two one-electron waves in acetonitrile collapsed to a single two
      electron wave in a RTIL such as butylmethyl imidazolium-BF4 (BMImBF4). In order
      to probe this effect over a wider range of mixed-molecular-solvent/RTIL
      solutions, the reduction process was studied using UV-vis
      spectroelectrochemistry. With the use of spectroelectrochemistry, it was possible
      to calculate readily the difference in E degrees 's between the first and second
      electron transfer (DeltaE12 degrees  = E1 degrees  - E2 degrees ) even when the
      two one-electron waves collapsed into a single two-electron wave. The spectra of
      the radical anion and dianion in BMImPF6 were obtained using evolving factor
      analysis (EFA). Using these spectra, the concentrations of DNB, DNB(-*), and
      DNB(2-) were calculated, and from these concentrations, the DeltaE12 degrees 
      values were calculated. Significant differences were observed when the
      bis(trifluoromethylsulfonyl)imide (NTf2) anion replaced the PF6(-) anion, leading
      to an irreversible reduction of DNB in BMImNTf2. The results were consistent with
      the protonation of DNB(2-), most likely by an ion pair between DNB(2-) and
      BMIm(+), which has been proposed by Minami and Fry. The differences in reactivity
      between the PF6(-) and NTf2(-) ionic liquids were interpreted in terms of the
      tight versus loose ion pairing in RTILs. The results indicated that
      nanostructural domains of RTILs were present in a mixed-solvent system. 

PMID- 24884070
TI  - Histamine H3 receptor activation counteracts adenosine A2A receptor-mediated
      enhancement of depolarization-evoked [3H]-GABA release from rat globus pallidus
      synaptosomes.
AB  - High levels of histamine H3 receptors (H3Rs) are found in the globus pallidus
      (GP), a neuronal nucleus in the basal ganglia involved in the control of motor
      behavior. By using rat GP isolated nerve terminals (synaptosomes), we studied
      whether H3R activation modified the previously reported enhancing action of
      adenosine A2A receptor (A2AR) stimulation on depolarization-evoked [(3)H]-GABA
      release. At 3 and 10 nM, the A2AR agonist CGS-21680 enhanced [(3)H]-GABA release
      induced by high K(+) (20 mM) and the effect of 3 nM CGS-21680 was prevented by
      the A2AR antagonist ZM-241385 (100 nM). The presence of presynaptic H3Rs was
      confirmed by the specific binding of N-alpha-[methyl-(3)H]-histamine to membranes
      from GP synaptosomes (maximum binding, Bmax, 1327 +/- 79 fmol/mg protein;
      dissociation constant, Kd, 0.74 nM), which was inhibited by the H3R ligands
      immepip, clobenpropit, and A-331440 (inhibition constants, Ki, 0.28, 8.53, and
      316 nM, respectively). Perfusion of synaptosomes with the H3R agonist immepip
      (100 nM) had no effect on K(+)-evoked [(3)H]-GABA release, but inhibited the
      stimulatory action of A2AR activation. In turn, the effect of immepip was blocked
      by the H3R antagonist clobenpropit, which had no significant effect of its own on
      K(+)-induced [(3)H]-GABA release. These data indicate that H3R activation
      selectively counteracts the facilitatory action of A2AR stimulation on GABA
      release from striato-pallidal projections. 

PMID- 24884099
TI  - Assimilation of polybrominated diphenyl ethers from microplastics by the marine
      amphipod, Allorchestes compressa.
AB  - Microplastic particles (MPPs; <5 mm) are found in skin cleansing soaps and are
      released into the environment via the sewage system. MPPs in the environment can
      sorb persistent organic pollutants (POPs) that can potentially be assimilated by
      organisms mistaking MPPs for food. Amphipods (Allorchestes compressa) exposed to
      MPPs isolated from a commercial facial cleansing soap ingested <=45 particles per
      animal and evacuated them within 36 h. Amphipods were exposed to polybrominated
      diphenyl ether (PBDEs) congeners (BDE-28, -47, -99, -100, -153, -154, and -183)
      in the presence or absence of MPPs. This study has demonstrated that PBDEs
      derived from MPPs can be assimilated into the tissue of a marine amphipod. MPPs
      reduced PBDE uptake compared to controls, but they caused greater proportional
      uptake of higher-brominated congeners such as BDE-154 and -153 compared to BDE-28
      and -47. While MPPs in the environment may lower PBDE uptake compared to
      unabsorbed free chemicals, our study has demonstrated they can transfer PBDEs
      into a marine organism. Therefore, MPPs pose a risk of contaminating aquatic food
      chains with the potential for increasing public exposure through dietary sources.
      This study has demonstrated that MPPs can act as a vector for the assimilation of
      POPs into marine organisms.

PMID- 24884108
TI  - Synthetic biologists spring into action at the 245th American Chemical Society
      National Meeting.
AB  - As the field of synthetic biology continues to define itself, it has merged
      concepts from many related areas of research: molecular biology, genetics,
      bioengineering, and chemistry. At the 2013 Spring American Chemical Society
      National Meeting in New Orleans, LA, this mixture was manifested in a wealth of
      sessions emphasizing the use of modern synthetic biological approaches to solve
      many of today's biggest chemical problems. As a result of the field's diverse yet
      pervasive nature, synthetic biology concepts were present in several of the
      conferences many divisions, including Biological Chemistry, Biochemical
      Technology, Cellulose and Renewable Materials, and several others. Here we offer
      a snapshot of some of the exciting research discussed in the dedicated synthetic
      biology sessions throughout the week. 

PMID- 24884109
TI  - Keystone Symposia conference on precision genome engineering and synthetic
      biology brings together players from both disciplines.

PMID- 24884132
TI  - Framework structures of interconnected layers in calcium iron arsenides.
AB  - The new calcium iron arsenide compounds Ca(n(n+1)/2)(Fe(1-x)M(x))(2+3n)M'(n(n
      1)/2)As((n+1)(n+2)/2) (n = 1-3; M = Nb, Pd, Pt; M' = ?, Pd, Pt) were synthesized
      and their crystal structures determined by single-crystal X-ray diffraction. The
      series demonstrates the structural flexibility of iron arsenide materials, which
      otherwise prefer layered structures, as is known from the family of iron-based
      superconductors. In the new compounds, iron arsenide tetrahedral layers are
      bridged by iron-centered pyramids, giving rise to so far unknown frameworks of
      interconnected FeAs layers. Channels within the structures are occupied with
      calcium and palladium or platinum, respectively. Common basic building blocks are
      identified that lead to a better understanding of the building principles of
      these structures and their relation to CaFe4As3.

PMID- 24884124
TI  - Oxidative remobilization of technetium sequestered by sulfide-transformed nano
      zerovalent iron.
AB  - Our previous study showed that formation of TcS2-like phases is favored over TcO2
      under sulfidic conditions stimulated by nano zerovalent iron. This study further
      investigates the stability of Tc(IV) sulfide upon reoxidation by solution
      chemistry, solid phase characterization, and X-ray absorption spectroscopy. Tc
      dissolution data showed that Tc(VII) reduced by sulfide-transformed nZVI has
      substantially slower reoxidation kinetics than Tc(VII) reduced by nZVI only. The
      initial inhibition of Tc(IV) dissolution at S/Fe = 0.112 is due to the redox
      buffer capacity of FeS, which is evidenced by the parallel trends in oxidation
      reduction potentials (ORP) and Tc dissolution kinetics. The role of FeS in
      inhibiting Tc oxidation is further supported by the Mossbauer spectroscopy and
      micro X-ray diffraction data at S/Fe = 0.112, showing persistence of FeS after 24
      h oxidation but complete oxidation after 120-h oxidation. X-ray absorption
      spectroscopy data for S/Fe = 0.011 showed significantly increasing percentages of
      TcS2 in the solid phase after 24-h oxidation, indicating stronger resistance of
      TcS2 to oxidation. At S/Fe = 0.112, the XAS results revealed significant
      transformation of Tc speciation from TcS2 to TcO2 after 120-h oxidation. Given
      that no apparent Tc dissolution occurred during this period, the speciation
      transformation might play a secondary role in hindering Tc oxidation.
      Collectively, the results indicate that sequestrating Tc as TcS2 under stimulated
      sulfate reduction is a promising strategy to improve the long-term stability of
      reduced Tc in subsurface remediation. 

PMID- 24884149
TI  - Engineered porous silicon counter electrodes for high efficiency dye-sensitized
      solar cells.
AB  - In this work, we demonstrate for the first time, the use of porous silicon (P-Si)
      as counter electrodes in dye-sensitized solar cells (DSSCs) with efficiencies
      (5.38%) comparable to that achieved with platinum counter electrodes (5.80%). To
      activate the P-Si for triiodide reduction, few layer carbon passivation is
      utilized to enable electrochemical stability of the silicon surface. Our results
      suggest porous silicon as a promising sustainable and manufacturable alternative
      to rare metals for electrochemical solar cells, following appropriate surface
      modification. 

PMID- 24884152
TI  - Redox chemistry of nickel(II) complexes supported by a series of noninnocent beta
      diketiminate ligands.
AB  - Nickel complexes of a series of beta-diketiminate ligands ((R)L(-), deprotonated
      form of 2-substituted N-[3-(phenylamino)allylidene]aniline derivatives (R)LH, R =
      Me, H, Br, CN, and NO2) have been synthesized and structurally characterized. One
      electron oxidation of the neutral complexes [Ni(II)((R)L(-))2] by AgSbF6 or
      [Ru(III)(bpy)3](PF6)3 (bpy = 2,2'-bipyridine) gave the corresponding metastable
      cationic complexes, which exhibit an EPR spectrum due to a doublet species (S =
      1/2) and a characteristic absorption band in near IR region ascribable to a
      ligand-to-ligand intervalence charge-transfer (LLIVCT) transition. DFT
      calculations have indicated that the divalent oxidation state of nickel ion
      (Ni(II)) is retained, whereas one of the beta-diketiminate ligands is oxidized to
      give formally a mixed-valence complex, [Ni(II)((R)L(-))((R)L(*))](+). Thus, the
      doublet spin state of the oxidized cationic complex can be explained by taking
      account of the antiferromagnetic interaction between the high-spin nickel(II) ion
      (S = 1) and the organic radical (S = 1/2) of supporting ligand. A single-crystal
      structure of one of the cationic complexes (R = H) has been successfully
      determined to show that both ligands in the cationic complex are structurally
      equivalent. On the basis of theoretical analysis of the LLIVCT band and DFT
      calculations as well as the crystal structure, the mixed-valence complexes have
      been assigned to Robin-Day class III species, where the radical spin is equally
      delocalized between the two ligands to give the cationic complex, which is best
      described as [Ni(II)((R)L(0.5*-))2](+). One-electron reduction of the neutral
      complexes with decamethylcobaltocene gave the anionic complexes when the ligand
      has the electron-withdrawing substituent (R = CN, NO2, Br). The generated anionic
      complexes exhibited EPR spectra due to a doublet species (S = 1/2) but showed no
      LLIVCT band in the near-IR region. Thus, the reduced complexes are best described
      as the d(9) nickel(I) complexes supported by two anionic beta-diketiminate
      ligands, [Ni(I)((R)L(-))2](-). This conclusion was also supported by DFT
      calculations. Substituent effects on the electronic structures of the three
      oxidation states (neutral, cationic, and anionic) of the complexes are
      systematically evaluated on the basis of DFT calculations. 

PMID- 24884156
TI  - New water-soluble ruthenium(II) terpyridine complexes for anticancer activity:
      synthesis, characterization, activation kinetics, and interaction with guanine
      derivatives.
AB  - With the aim of assessing whether ruthenium(II) compounds with meridional
      geometry might be utilized as potential antitumor agents, a series of new, water
      soluble, monofunctional ruthenium(II) complexes of the general formula mer
      [Ru(L3)(N-N)X][Y]n (where L3 = 2,2':6',2"-terpyridine (tpy) or 4'-chloro
      2,2':6',2"-terpyridine (Cl-tpy), N-N = 1,2-diaminoethane (en), 1,2
      diaminocyclohexane (dach), or 2,2'-bipyridine (bpy); X = Cl or dmso-S; Y = Cl,
      PF6, or CF3SO3; n = 1 or 2, depending on the nature of X) were synthesized. All
      complexes were fully characterized by elemental analysis and spectroscopic
      techniques (IR, UV/visible, and 1D and 2D NMR), and for three of them, i.e.,
      [Ru(Cl-tpy)(bpy)Cl][Cl] (3Cl), [Ru(Cl-tpy)(en)(dmso-S)][Y]2 [Y = PF6 (6PF6),
      CF3SO3 (6OTf)] and [Ru(Cl-tpy)(bpy)(dmso-S)][CF3SO3]2 (8OTf), the X-ray structure
      was also determined. The new terpyridine complexes, with the exception of 8, are
      well soluble in water (>25 mg/mL). (1)H and (31)P NMR spectroscopy studies
      performed on the three selected complexes [Ru(Cl-tpy)(N-N)Cl](+) [N-N = en (1),
      dach (2), and bpy (3)] demonstrated that, after hydrolysis of the Cl ligand, they
      are capable of interacting with guanine derivatives [i.e., 9-methylguanine (9MeG)
      or guanosine-5'-monophosphate (5'-GMP)] through N7, forming monofunctional
      adducts with rates and extents that depend strongly on the nature of N-N: 1 ~ 2 ?
      3. In addition, compound 1 shows high selectivity toward 5'-GMP compared to
      adenosine-5'-monophosphate (5'-AMP), in a competition experiment. Quantitative
      kinetic investigations on 1 and 2 were performed by means of UV/visible
      spectroscopy. Overall, the complexes with bidentate aliphatic diamines proved to
      be superior to those with bpy in terms of solubility and reactivity (i.e.,
      release of Cl(-) and capability to bind guanine derivatives). Contrary to the
      chlorido compounds, the corresponding dmso derivatives proved to be inert (viz.,
      they do not release the monodentate ligand) in aqueous media. 

PMID- 24884167
TI  - Lanthanide metalloligand strategy toward d-f heterometallic metal-organic
      frameworks: magnetism and symmetric-dependent luminescent properties.
AB  - On the basis of lanthanide metalloligands, [Ln(ODA)3](3-) (H2ODA = oxydiacetic
      acid), three series of d-f heterometallic metal-organic frameworks,
      {[Co(H2O)6].[Ln2(ODA)6Co2].6H2O}n [1; Ln = Gd (1a), Dy (1b), and Er (1c)],
      {[Ln2(ODA)6Cd3(H2O)6].mH2O}n [2; Ln = Pr (2a), Nd (2b), Sm (2c), Eu (2d), and Dy
      (2e), m = 9, 6, or 3], and {[Cd(H2O)6].[Ln2(ODA)6Cd2].mH2O}n [3; Ln = Dy (3a), Ho
      (3b), Er (3c), Tm (3d), and Lu (3e), m = 6 or 12], were designed and synthesized
      by a solvent volatilization and hydrothermal method. Magnetic investigation of 1
      reveals the ferromagnetic interactions between the metal ions. In 2, Ln(III) ions
      occupied the inversion centers, which are confirmed by the fact that the emission
      intensity ratio of (5)D0 -> (7)F1 to (5)D0 -> (7)F2 of the Eu(III) ion is much
      more than 3 in 2d. It is worth noting that, in 2d, the intensity ratio I((5)D0
      >(7)F1)/I((5)D0->(7)F2) could decrease significantly upon the introduction of
      different hydrophilic guest molecules, which implies that the luminescent
      properties of 2d have a strong dependence on the geometry of the first
      coordination sphere of the Eu(III) ion. 

PMID- 24884171
TI  - Bifunctional Crosslinking Agents Enhance Anion Exchange Membrane Efficacy for
      Vanadium Redox Flow Batteries.
AB  - A series of cross-linked fluorinated poly (aryl ether oxadiazole) membranes
      (FPAEOM) derivatized with imidazolium groups were prepared. Poly (N
      vinylimidazole) (PVI) was used as the bifunctional cross-linking agent to: a)
      lower vanadium permeability, b) enhance dimensional stability, and c)
      concomitantly provide added ion exchange capacity in the resultant anion exchange
      membranes. At a molar ratio of PVI to FPAEOM of 1.5, the resultant membrane
      (FPAEOM-1.5 PVI) had an ion exchange capacity of 2.2 meq g-1, a vanadium
      permeability of 6.8*10-7 cm2 min-1, a water uptake of 68 wt.%, and an ionic
      conductivity of 22.0 mS cm-1, all at 25 degrees C. Single cells prepared with the
      FPAEOM-1.5 PVI membrane exhibited a higher coulombic efficiency (> 92%) and
      energy efficiency (> 86%) after 40 test cycles in vanadium redox flow battery.
      The imidazolium cation showed high chemical stability in highly acidic and
      oxidizing vanadium solution as opposed to poor stability in alkaline solutions.
      Based on our DFT studies, this was attributed to the lower HOMO energy (-7.265
      eV) of the HSO4- ion (compared to the OH- ion; -5.496 eV) and the larger HOMO
      LUMO energy gap (6.394 eV) of dimethylimidazolium bisulfate ([DMIM] [HSO4]) as
      compared to [DMIM] [OH] (5.387 eV).

PMID- 24884163
TI  - Adenine nucleotide translocase is acetylated in vivo in human muscle: Modeling
      predicts a decreased ADP affinity and altered control of oxidative
      phosphorylation.
AB  - Proteomics techniques have revealed that lysine acetylation is abundant in
      mitochondrial proteins. This study was undertaken (1) to determine the
      relationship between mitochondrial protein acetylation and insulin sensitivity in
      human skeletal muscle, identifying key acetylated proteins, and (2) to use
      molecular modeling techniques to understand the functional consequences of
      acetylation of adenine nucleotide translocase 1 (ANT1), which we found to be
      abundantly acetylated. Eight lean and eight obese nondiabetic subjects had
      euglycemic clamps and muscle biopsies for isolation of mitochondrial proteins and
      proteomics analysis. A number of acetylated mitochondrial proteins were
      identified in muscle biopsies. Overall, acetylation of mitochondrial proteins was
      correlated with insulin action (r = 0.60; P < 0.05). Of the acetylated proteins,
      ANT1, which catalyzes ADP-ATP exchange across the inner mitochondrial membrane,
      was acetylated at lysines 10, 23, and 92. The extent of acetylation of lysine 23
      decreased following exercise, depending on insulin sensitivity. Molecular
      dynamics modeling and ensemble docking simulations predicted the ADP binding site
      of ANT1 to be a pocket of positively charged residues, including lysine 23.
      Calculated ADP-ANT1 binding affinities were physiologically relevant and
      predicted substantial reductions in affinity upon acetylation of lysine 23.
      Insertion of these derived binding affinities as parameters into a complete
      mathematical description of ANT1 kinetics predicted marked reductions in adenine
      nucleotide flux resulting from acetylation of lysine 23. Therefore, acetylation
      of ANT1 could have dramatic physiological effects on ADP-ATP exchange.
      Dysregulation of acetylation of mitochondrial proteins such as ANT1 therefore
      could be related to changes in mitochondrial function that are associated with
      insulin resistance.

PMID- 24884196
TI  - Responsive nature of 1,2,4,5-tetrakis(2-pyridylthiomethyl)benzene toward group 12
      metal nitrates: activity of coordinated nitrate in metal complexes.
AB  - This study provides a detailed analysis on the responsive behavior of 1,2,4,5
      tetrakis(2-pyridylthiomethyl)benzene (L) toward group 12 metal nitrates in both
      aqueous and nonaqueous media. The ligand L proved to be an environmentally
      responsive species, and structural investigations of its complexes with
      respective M(NO3)2 (M = Zn, Cd, and Hg) allowed one to remark on the inherent
      activity of the nitrate ion, resulting in a distinctively higher coordination
      number and dimensionality to the metal cations. 

PMID- 24884204
TI  - Hybrid self-healing matrix using core-shell nanofibers and capsuleless
      microdroplets.
AB  - In this work, we developed novel self-healing anticorrosive hierarchical coatings
      that consist of several components. Namely, as a skeleton we prepared a core
      shell nanofiber mat electrospun from emulsions of cure material (dimethyl
      methylhydrogen siloxane) in a poly(acrylonitrile) (PAN) solution in
      dimethylformamide. In these nanofibers, cure is in the core, while PAN is in the
      shell. The skeleton deposited on a protected surface is encased in an epoxy-based
      matrix, which contains emulsified liquid droplets of dimethylvinyl-terminated
      dimethylsiloxane resin monomer. When such hierarchical coatings are damaged, cure
      is released from the nanofiber cores and the resin monomer, released from the
      damaged matrix, is polymerized in the presence of cure. This polymerization and
      solidification process takes about 1-2 days and eventually heals the damaged
      material when solid poly(dimethylsiloxane) resin is formed. The self-healing
      effect was demonstrated using an electrochemical analogue of the scanning
      vibrating electrode technique. Damaged samples were left for 2 days. After that,
      the electric current through a damaged coating was found to be negligibly small
      for the samples with self-healing properties. On the other hand, for the samples
      without self-healing properties, the electric current was significant. 

PMID- 24884208
TI  - Energy transfer from Sm3+ to Eu3+ in red-emitting phosphor LaMgAl11O19:Sm3+, Eu3+
      for solar cells and near-ultraviolet white light-emitting diodes.
AB  - The red-emitting phosphor LaMgAl11O19:Sm(3+), Eu(3+) was prepared by solid-state
      reaction at 1600  degrees C for 4 h. The phase formation, luminescence
      properties, and energy transfer from Sm(3+) to Eu(3+) were studied. With the
      addition of 5 mol % Sm(3+) as the sensitizer, the excitation wavelength of
      LaMgAl11O19:Eu(3+) phosphor was extended from 464 to 403 nm, and the emission
      intensity under the excitation at 403 nm was also enhanced. The host material
      LaMgAl11O19 could contain the high doping content of Eu(3+) (20 mol %) without
      concentration quenching. This energy transfer from Sm(3+) to Eu(3+) was confirmed
      by the decay times of energy donor Sm(3+). The mechanism of energy transfer
      (Sm(3+) -> Eu(3+)) was proved to be quadrupole-quadrupole interaction. Under the
      403 nm excitation at 150  degrees C, the emission intensities of the
      characteristic peaks of Sm(3+) and Eu(3+) in LaMgAl11O19:0.05Sm(3+), 0.2Eu(3+)
      phosphor were decreased to 65% and 56% of the initial intensities at room
      temperature, and the relatively high activation energy proved that this phosphor
      had a good thermal stability. The CIE coordinate was calculated to be (x = 0.601,
      y = 0.390). The LaMgAl11O19:0.05Sm(3+), 0.2Eu(3+) phosphor is a candidate for
      copper phthalocyanine-based solar cells and white light-emitting diodes. 

PMID- 24884175
TI  - Nonaggregated alpha-synuclein influences SNARE-dependent vesicle docking via
      membrane binding.
AB  - alpha-Synuclein (alpha-Syn), a major component of Lewy body that is considered as
      the hallmark of Parkinson's disease (PD), has been implicated in neuroexocytosis.
      Overexpression of alpha-Syn decreases the neurotransmitter release. However, the
      mechanism by which alpha-Syn buildup inhibits the neurotransmitter release is
      still unclear. Here, we investigated the effect of nonaggregated alpha-Syn on
      SNARE-dependent liposome fusion using fluorescence methods. In ensemble in vitro
      assays, alpha-Syn reduces lipid mixing mediated by SNAREs. Furthermore, with the
      more advanced single-vesicle assay that can distinguish vesicle docking from
      fusion, we found that alpha-Syn specifically inhibits vesicle docking, without
      interfering with the fusion. The inhibition in vesicle docking requires alpha-Syn
      binding to acidic lipid containing membranes. Thus, these results imply the
      existence of at least two mechanisms of inhibition of SNARE-dependent membrane
      fusion: at high concentrations, nonaggregated alpha-Syn inhibits docking by
      binding acidic lipids but not v-SNARE; on the other hand, at much lower
      concentrations, large alpha-Syn oligomers inhibit via a mechanism that requires v
      SNARE interaction [ Choi et al. Proc. Natl. Acad. Sci. U. S. A. 2013 , 110 ( 10
      ), 4087 - 4092 ]. 

PMID- 24884214
TI  - The impact of the number of young adults on an inpatient psychiatric unit.
AB  - Age has been shown to contribute to aggression in inpatient settings. Studies
      that examine violence in inpatient settings have shown that younger patients have
      a higher tendency of aggressive behavior toward staff and other patients
      (Aquilina, 1991; Hillbrand, Foster, & Spitz, 1996; James, Fineberg, Shah, &
      Priest, 1990; Nijman, Allerti, Merckelbach, a Campo, & Rovelli, 1997; Owen,
      Tarantello, Jones, & Tennant, 1998).However, though younger age has been
      associated with higher rates of violence, no studies have been conducted to
      assess the impact of multiple young adults on the functioning of an inpatient
      unit. This study evaluates the effect of the number of young adults on unit
      functioning and whether young adults mix poorly with other age groups. 

PMID- 24884211
TI  - Nucleic acid-scavenging electrospun nanofibrous meshes for suppressing
      inflammatory responses.
AB  - Fragmented nucleic acids are potent stimulators for inflammatory responses
      provoking pathological outcomes by activating adaptive immunity. In this study,
      highly cationic surfaces were prepared on electrospun nanofibrous meshes to
      scavenge nucleic acids to the surfaces. Poly(epsilon-caprolactone) [PCL]
      poly(ethylenimine) [PEI] block copolymers were synthesized by coupling the
      carboxyl-terminated PCL to the primary amines of branched PEI. Polymeric
      solutions composed of PCL-PEI and PCL were electrospun to nanofibrous mats, and
      the surfaces were further methylated to prepare highly cationic surfaces on the
      mats. Raman spectroscopy revealed that the presence of increased methylated
      amines on the surfaces of the mats compared to unmodified mats. The methylated
      surfaces showed significant increases of wettability after methylation,
      suggesting highly charged surfaces caused by methylation of the primary amines.
      When the blend ratio of PCL-PEI was increased, the scavenged DNA was also
      increased, and the methylation further strengthened the scavenging ability of the
      mats. Fluorescently labeled oligodeoxynucleic acids were significantly adsorbed
      on the surface of the mats depending on the amounts of PCL-PEI and the degree of
      methylation. In the presence of the methylated nanofibrous mats, inflammatory
      responses induced by CpG oligonucleotides in murine macrophages were
      significantly reduced, which was confirmed by measuring inflammatory cytokine
      levels including TNF-alpha and IFN-gamma. 

PMID- 24884227
TI  - Hierarchical mesoporous MnO2 superstructures synthesized by soft-interface method
      and their catalytic performances.
AB  - To obtain a highly efficient and stable heterogeneous catalyst in catalytic wet
      hydrogen peroxide oxidation, we have successfully synthesized hierarchical
      mesoporous manganese dioxide (MnO2) superstructures by a facile and environmental
      friendly method on a soft-interface between CH2Cl2 and H2O without templates. The
      main crystal phase of as-prepared MnO2 was proved to be epsilon-MnO2 by X-ray
      diffraction techniques. The structure characterizations indicated that the
      hierarchical MnO2 superstructures were composed of urchin-like MnO2 hollow
      submicrospheres assembled by one-dimension nanorods building blocks with rich
      mesoporosity. The nitrogen sorption analysis confirmed that the as-synthesized
      MnO2 has an average pore diameter of 5.87 nm, mesoporous volume of 0.451 cm(3) g(
      1), and specific surface area of 219.3 m(2) g(-1). Further investigations
      revealed that a possible formation mechanism of this unique hierarchical
      superstructure depended upon the synthesis conditions. The catalytic performances
      of the hierarchical mesoporous MnO2 superstructures were evaluated in catalytic
      degradation of methylene blue in the presence of H2O2 at neutral pH, which
      demonstrated highly efficient catalytic degradation of the organic pollutant
      methylene blue using hierarchical mesoporous MnO2 superstructures as catalyst at
      room temperature. 

PMID- 24884229
TI  - Glycerol-mediated nanostructure modification leading to improved transparency of
      porous polymeric scaffolds for high performance 3D cell imaging.
AB  - Glycerol is among the most commonly used optical clearing agents for tissues
      clearance largely due to refractive index (RI) matching between glycerol and the
      submerged tissues. Here we applied glycerol as structure modifier at both
      macroscopic (as porogen) and nanoscopic (as nanostructure ameliorant) scales to
      fabricate transparent porous scaffolds made from poly(ethylene glycol) (PEG) as
      well as other widely used biomaterials (e.g., PLGA, PA, or gelatin), whose
      nanostructures, in the scale of light wavelength, dominantly improved the optical
      transmittance of the scaffolds even when immersed in RI mismatched medium (e.g.,
      culture medium or water). We further exploited the clearing mechanisms based on
      Mie scattering theory, illustrating that conformational changes of polymer chains
      induced by solvent effects of glycerol enhanced the anisotropy (i.e., directional
      alignment) of the nanostructures, leading to reduced crystallinity and scattering
      of the resulted PEG scaffolds. Our findings represent the first and systematic
      demonstration with both experimental and theoretical evidence in effectively
      clearing porous polymeric scaffolds by mechanisms other than RI matching, which
      could tackle the limitations of current optical imaging of cells cultured within
      three-dimensional (3D) opaque porous scaffolds, such as poor visibility, low
      spatial resolution, and small penetration depth. 

PMID- 24884230
TI  - Synthesis and structure of an open-cage thiafullerene C69S: reactivity
      differences of an open-cage C70 tetraketone relative to its C60 analogue.
AB  - An open-cage C70 fullerene with a 13-membered ring-opening and a bis(hemiacetal)
      moiety was synthesized by the reaction of the corresponding open-cage C70
      diketone with nucleophilic oxidizing agents. The size of the cage opening could
      be expanded by a subsequent dehydration reaction. Reaction of the thus obtained
      open-cage C70 tetraketone with elemental sulfur in the presence of
      tetrakis(dimethylamino)ethylene resulted in the formation of the first example of
      an open-cage C69S thiafullerene with a 12-membered ring-opening. The formation of
      this sulfur-containing heterofullerene reflects a significantly different
      chemical reactivity for the open-cage C70 tetraketone relative to its C60
      analogue. The structures of all novel compounds were unambiguously determined by
      single crystal X-ray diffraction analyses, in addition to which the
      electrochemical properties of the thiafullerene C69S were examined and compared
      with those of the corresponding C70 analogue. 

PMID- 24884237
TI  - Ultra-low-energy three-dimensional oxide-based electronic synapses for
      implementation of robust high-accuracy neuromorphic computation systems.
AB  - Neuromorphic computing is an attractive computation paradigm that complements the
      von Neumann architecture. The salient features of neuromorphic computing are
      massive parallelism, adaptivity to the complex input information, and tolerance
      to errors. As one of the most crucial components in a neuromorphic system, the
      electronic synapse requires high device integration density and low-energy
      consumption. Oxide-based resistive switching devices have been shown to be a
      promising candidate to realize the functions of the synapse. However, the
      intrinsic variation increases significantly with the reduced spike energy due to
      the reduced number of oxygen vacancies in the conductive filament region. The
      large resistance variation may degrade the accuracy of neuromorphic computation.
      In this work, we develop an oxide-based electronic synapse to suppress the
      degradation caused by the intrinsic resistance variation. The synapse utilizes a
      three-dimensional vertical structure including several parallel oxide-based
      resistive switching devices on the same nanopillar. The fabricated three
      dimensional electronic synapse exhibits the potential for low fabrication cost,
      high integration density, and excellent performances, such as low training energy
      per spike, gradual resistance transition under identical pulse training scheme,
      and good repeatability. A pattern recognition computation is simulated based on a
      well-known neuromorphic visual system to quantify the feasibility of the three
      dimensional vertical structured synapse for the application of neuromorphic
      computation systems. The simulation results show significantly improved
      recognition accuracy from 65 to 90% after introducing the three-dimensional
      synapses. 

PMID- 24884240
TI  - High level biosynthesis of a silk-elastin-like protein in E. coli.
AB  - Silk-elastin-like proteins (SELPs) have enormous potential for use as
      customizable biomaterials in numerous biomedical and materials applications, yet
      success in harnessing this potential has been limited by the lack of a
      commercially viable industrially relevant production process. We have developed a
      scalable fed-batch production approach which enables a SELP volumetric
      productivity of 4.3 g L(-1) with E. coli BL21(DE3). This is the highest SELP
      productivity reported to date and is 50-fold higher than that reported by other
      groups. As compared to typical fed-batch processes, high preinduction growth
      rates and low inducer and oxygen concentrations are allowed whereas reduced
      postinduction feeding rates are preferred. Limiting factors were identified and
      productivity was found to be strongly influenced by a trade-off between the rate
      of production and plasmid stability. The process developed is robust,
      reproducible, and applicable to scale up to the industrial level and moves these
      biopolymers a step closer to the marketplace. 

PMID- 24884258
TI  - Production of Bombyx mori silk fibroin incorporated with unnatural amino acids.
AB  - Silk fibroin incorporated with unnatural amino acids was produced by in vivo
      feeding of p-chloro-, p-bromo-, and p-azido-substituted analogues of L
      phenylalanine (Phe) to transgenic silkworms (Bombyx mori) that expressed a mutant
      of phenylalanyl-tRNA synthetase with expanded substrate recognition capabilities
      in silk glands. Cutting down the content of Phe in the diet was effective for
      increasing the incorporation of Phe analogues but simultaneously caused a
      decrease of fibroin production. The azide groups incorporated in fibroin were
      active as chemical handles for click chemistry in both the solubilized and the
      solid (fibrous) states. The azides survived degumming in the boiling alkaline
      solution that is required for complete removal of the sericin layer,
      demonstrating that AzPhe-incorporated silk fibroin could be a versatile platform
      to produce "clickable" silk materials in various forms. This study indicates the
      huge potential of UAA mutagenesis as a novel methodology to alter the
      characteristics of B. mori silk.

PMID- 24884274
TI  - High-pressure chemical biology and biotechnology.

PMID- 24884284
TI  - Detection of melamine in foods using terahertz time-domain spectroscopy.
AB  - The aim of this study was to investigate the feasibility of detecting melamine in
      foodstuffs using terahertz imaging. The terahertz (THz) spectra and images of
      melamine mixtures were obtained in the frequency range of 0.1-3 THz at room
      temperature using THz time-domain spectroscopy. Characteristic absorption peaks
      of melamine were found at 2, 2.26, and 2.6 THz, and these peaks showed the same
      frequencies in the different food matrices. At 2 THz, the THz images of melamine
      were dose-dependently distinguishable from those of food components with or
      without the packaging materials used. The calibration curve of melamine showed a
      regression coefficient (R(2)) of >0.913 and a detection limit of <13%. These
      results suggest that terahertz imaging has the potential to be used for the
      qualitative detection of melamine in food as a nondestructive analytical tool. 

PMID- 24884286
TI  - Free energy of PAMAM dendrimer adsorption onto model biological membranes.
AB  - We investigated the thermodynamic, structural, and dynamics changes in dendrimer
      membrane systems during dendrimer adsorption to biological membrane systems by
      combining atomistic molecular dynamics simulations with umbrella sampling
      techniques to understand the atomistic interactions between the dendrimer and
      biological membranes. An ethylenediamine core polyamidoamine dendrimer
      (generation 3) with amine terminal groups and both zwitterionic dipalmitoyl
      phosphatidyl-choline (DPPC) and anionic palmitoyl-oleoyl-phosphatidyl glycerol
      (POPG) lipid bilayer membranes were used as the model dendrimer and biological
      membranes, respectively, in this study. The free energy of the dendrimer
      adsorption onto two model membranes with different charge states was
      quantitatively determined. For the zwitterionic DPPC membrane, the dendrimer has
      a minimum free energy of approximately 50 kcal/mol, which is 15 kcal/mol higher
      than that observed in previous studies. The dominant contribution to the
      adsorption potential energy is the van der Waals attraction between the dendrimer
      and the DPPC membrane. However, the anionic POPG membrane pulls the positively
      charged dendrimer with an attractive mean force of about 200 pN, finally
      positioning the dendrimer in the membrane headgroup region. As a result of these
      strong attractive dendrimer and membrane interactions, the dendrimer structurally
      undergoes the transition from spherical to a pancake conformation, which slows
      its lateral mobility, especially in the presence of the POPG membrane. The
      bilayer lipid membranes are also perturbed by the dendrimer adsorption. 

PMID- 24884298
TI  - Formation of ethane from mono-methyl palladium(II) complexes.
AB  - This article describes the high-yielding and selective oxidatively induced
      formation of ethane from mono-methyl palladium complexes. Mechanistic details of
      this reaction have been explored via both experiment and computation. On the
      basis of these studies, a mechanism involving methyl group transmetalation
      between Pd(II) and Pd(IV) interediates is proposed. 

PMID- 24884299
TI  - Strategies, barriers, and motivation for weight loss among veterans living with
      schizophrenia.
AB  - OBJECTIVE: Weight loss programs for veterans living with schizophrenia have
      demonstrated mixed efficacy, highlighting unique obstacles faced by this
      population. Data from a large national sample provide an opportunity to
      characterize the unique factors related to weight loss for veterans with
      schizophrenia. The present study compared veterans living with schizophrenia (n =
      5,388) to veterans with no mental health diagnoses (n = 81,422) on responses to
      the MOVE!23, a multidimensional assessment of factors related to weight
      management. METHODS: Responses to the MOVE!23 between August, 2005 and May, 2013
      by veterans with a body mass index in the overweight or obese range were used to
      describe clinical characteristics, current strategies, perceived barriers, stages
      of readiness, and importance of and confidence to change behaviors related to
      their weight management. RESULTS: Both groups reported similar stages of
      readiness and high ratings of importance and confidence regarding weight loss
      behaviors. Compared with veterans with no mental health diagnoses, over 5 times
      as many veterans living with schizophrenia reported smoking to control weight,
      and a greater number endorsed 18 of the 21 barriers to modifying eating and
      physical activity. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: RESULTS highlight
      the necessity of addressing healthy lifestyles from a holistic perspective for
      all veterans. Adding regular physical activity as part of daily treatment may
      address the accessibility, safety concerns, and lack of social support reported
      as physical activity barriers. Increased access to healthier food choices and
      addressing smoking in conjunction with weight loss are also warranted.

PMID- 24884300
TI  - Measurement equivalence of the Empowerment Scale for White and Black persons with
      severe mental illness.
AB  - OBJECTIVE: The current study examined the measurement equivalence on a measure of
      personal empowerment for Black and White consumers of mental health services.
      METHOD: Confirmatory factor analysis was used to assess measurement equivalence
      of the 28-item Empowerment Scale (Rogers, Chamberlin, Ellison, & Crean, 1997),
      using data from 1,035 White and 301 Black persons with severe mental illness.
      RESULTS: Metric invariance of the Empowerment Scale was supported, in that the
      factor structure and loadings were equivalent across groups. Scalar invariance
      was violated on 3 items; however, the impact of these items on scale scores was
      quite small. Finally, subscales of empowerment tended to be more highly
      intercorrelated for Black than for White respondents. CONCLUSIONS AND
      IMPLICATIONS FOR PRACTICE: RESULTS generally support the use of Empowerment Scale
      for ethnic group comparisons. However, subtle differences in the psychometric
      properties of this measure suggest that Black and White individuals may
      conceptualize the construct of empowerment in different ways. Specifically, Black
      respondents had a lower threshold for endorsing some items on the self-esteem and
      powerlessness dimensions. Further, White respondents viewed the 3 dimensions of
      empowerment (self-esteem, powerlessness, and activism) as more distinct, whereas
      these 3 traits were more strongly interrelated for Blacks.

PMID- 24884301
TI  - Conceptions of time in children treated for malignant cerebellar tumours.
AB  - PRIMARY OBJECTIVE: Conceptions of time in children having survived malignant
      cerebellar tumours (CT) and healthy children matched for chronological age (HCCA)
      were compared, knowing that the cerebellum has been involved in time perception.
      METHODS AND PROCEDURE: Study participants included 20 children with CT (13 boys)
      and 20 HCCA (10 boys) aged 6-12 years. All children with CT were at least 1 year
      after the end of treatment without relapse. A time questionnaire (TQ) exploring
      duration of daily activities, time units, planning and diachronic thinking was
      used, as well as a video animation (VA) displaying cyclic and linear time. MAIN
      OUTCOMES AND RESULTS: Children with CT obtained similar results as HCCA for time
      units, planning and diachronic thinking, but showed more difficulties than
      controls in estimating the duration of daily activities and understanding linear
      and cyclic time concepts (VA). CONCLUSIONS: These findings are not in favour of
      impaired time conceptions in children with CT and are probably linked to the
      specific life experience among children treated for a malignant pathology, rather
      than to the role of the cerebellum in time processing.

PMID- 24884306
TI  - The capsule endoscopy "suspected blood indicator" (SBI) for detection of active
      small bowel bleeding: no active bleeding in case of negative SBI.
AB  - OBJECTIVE: Capsule endoscopy (CE) is the gold standard to diagnose small bowel
      bleeding. The "suspected blood indicator" (SBI) offers an automated detection of
      active small bowel bleeding but validity of this technique is unknown. The
      objective was to analyze specificity and sensitivity of the SBI using the second
      small bowel capsule generation for the detection of active bleeding. METHODS:
      This is a retrospective analysis of all patients (199) who attended our clinic
      for CE from June 2008 through March 2013. The second-generation PillCam SB 2
      capsule was used for detection of (1) luminal blood content and (2) potentially
      responsible small bowel lesions. The findings of an independent investigator were
      correlated to SBI findings and a number of SBI markings were analyzed by a
      receiver operating characteristic (ROC). RESULTS: In 157/199 cases, no sign of
      active bleeding or altered blood was detected. One hundred and thirty-seven of
      these 157 cases provided at least one SBI marking and a mean of 18.4 positive SBI
      markings per record were found. In 20 cases, neither SBI nor the human
      investigator detected abnormalities. Thirteen patients showed investigator
      detected minor bleeding with mean SBI findings of 36 positive screenshots per
      record. When major bleeding was diagnosed by the investigator (n = 29), SBI
      detected a mean of 46.6 SBI-positive markings. SBI turned positive in 179
      patients, whereas the investigator detected active bleeding in 42 cases. All
      patients with active bleeding were detected by SBI (sensitivity 100%, specificity
      13%). ROC analysis revealed 51.0 SBI markings being the optimal cutoff for active
      versus no bleeding (sensitivity 79.1%, specificity 90.4%, misclassification of
      15.3%). CONCLUSION: The new SBI software is a reliable tool to exclude active
      bleeding and/or major lesions but analysis of the CE video by a trained
      investigator is still important for the detection of lesions responsible for past
      bleeding.

PMID- 24884307
TI  - The status of health communication: education and employment outlook for a
      growing field.
AB  - Using an online survey of health communication practitioners and academics (N =
      372), this study investigates the educational background (degrees, knowledge,
      skills, and coursework) perceived to be important for employment in health
      communication. It provides an update on what may be needed in terms of graduate
      education, as well as which areas may be emerging as most important in the field.
      The purpose is to inform students, educators, administrators, and practitioners
      about the current status and possible future trends in health communication
      education and practice.

PMID- 24884302
TI  - Anti-tumor necrosis factor agents reduce corticosteroid use compared with
      azathioprine in patients with Crohn's disease.
AB  - BACKGROUND: Corticosteroids are effective for inducing remission of Crohn's
      disease, but should not be used long term due to risk of adverse events. Benefits
      of immunosuppressants (e.g., azathioprine) and anti tumor necrosis factor (anti
      TNF) agents include reduced reliance on corticosteroid-based therapies and
      avoidance of corticosteroid-associated adverse events. Our aim was to evaluate
      corticosteroid-sparing effects in patients with Crohn's disease upon being newly
      initiated on an anti-TNFalpha agent or azathioprine. METHODS: An analysis of US
      patient claims data from January 2008 to October 2011 was conducted using Truven
      Health MarketScan Research databases. Corticosteroid-sparing within 12 and 24
      months after initiation of an anti-TNF agent (adalimumab, certolizumab pegol, or
      infliximab) or azathioprine was evaluated. RESULTS: In total, 2900 patients
      received a prescription for corticosteroids within the 6 month period before the
      initiation of an anti-TNF agent (63%) or azathioprine (37%). When certolizumab
      pegol, infliximab, or adalimumab were collectively compared with azathioprine,
      patients initiated on an anti-TNF agent avoided further prescriptions for
      corticosteroids at a greater rate than patients receiving azathioprine at 12 (43%
      vs. 27%, respectively; P < 0.0001) and 24 months (33% vs. 23%, respectively; P =
      0.028). Individually, all anti-TNF agents showed higher rates of corticosteroid
      sparing compared with azathioprine at 12 (P < 0.0001-0.011), but not 24 months (P
      = 0.0086-0.24). Key limitations of this study include lack of data regarding
      disease severity, response and assumptions of improvement, and compliance.
      CONCLUSIONS: Patients with Crohn's disease were able to avoid new prescriptions
      for corticosteroids at a statistically higher rate when treated with an anti-TNF
      agent. These results demonstrate that the anti-TNF agents are superior to
      azathioprine for minimizing exposure to corticosteroids.

PMID- 24884309
TI  - Effect of seed roasting on canolol, tocopherol, and phospholipid contents,
      Maillard type reactions, and oxidative stability of mustard and rapeseed oils.
AB  - This work was carried out to study the effect of roasting on different
      compositional parameters and oil oxidative stability of three Brassica species
      (Brassica juncea (BJ), B. juncea var. oriental (BJO), and Brassica napus
      (rapeseed, RS)). After 10 min of roasting at 165  degrees C, canolol contents of
      BJ, BJO, and RS oil reached 297.8, 171.6, and 808.5 MUg/g, and the phospholipid
      phosphorus contents reached 453.6, 342.6, and 224.2 MUg/g oil, respectively. The
      BJ and BJO seeds showed more prominent browning reactions than RS, due to the
      presence of higher amounts of reducing sugars, lysine, arginine and the
      occurrence of Maillard type browning reactions of phospholipids. The UV-visible
      spectra, fluorescence, and pyrrole content showed the presence of browning
      reaction products in the roasted seed oils. Roasting increased the oxidative
      stability of all varieties. Canolol formation could only partially explain such
      observations. Other roasting effects such as phospholipid extraction and Maillard
      type browning reaction products were also responsible for the increased
      stability. 

PMID- 24884311
TI  - Role of plerixafor in autologous stem cell mobilization with vinorelbine
      chemotherapy and granulocyte-colony stimulating factor in patients with myeloma:
      a phase II study (PAV-trial).
AB  - Current practice in Switzerland for the mobilization of autologous stem cells in
      patients with myeloma is combining vinorelbine chemotherapy and granulocyte
      colony stimulating factor (G-CSF) cytokine stimulation. We prospectively
      investigated adding intravenous plerixafor to the vinorelbine/G-CSF combination
      (VGP), and compared it with vinorelbine/plerixafor (VP) and G-CSF/plerixafor (GP)
      combinations. In a final cohort (VP-late), plerixafor was given on the first day
      of CD34 + cells increasing to > 15,000/mL peripheral blood. Four consecutive
      cohorts of 10 patients with myeloma were studied. We observed that intravenously
      administered plerixafor can be safely combined with vinorelbine/G-CSF. VGP was
      superior in mobilizing peripheral stem and progenitor cells compared to the three
      double combinations (VP, GP and VP-late), and GP mobilized better than VP. Our
      data indicate that the triple combination of VGP is an efficient strategy to
      collect autologous CD34 + cells, with G-CSF contributing predominantly in this
      concept. Plerixafor can be safely added to G-CSF and/or vinorelbine chemotherapy.

PMID- 24884313
TI  - Translocation (18;22)(q21;q11.2) in B-cell lymphoproliferative disorders: a
      report of six cases.

PMID- 24884312
TI  - Response monitoring of infant acute myeloid leukemia treatment by quantification
      of the tumor specific MLL-FNBP1 fusion gene.

PMID- 24884314
TI  - Higher percentage of CD34 + CD38- cells detected by multiparameter flow cytometry
      from leukapheresis products predicts unsustained complete remission in acute
      myeloid leukemia.
AB  - Relapse in acute myeloid leukemia (AML) after chemotherapy reflects the
      persistence of resistant leukemia stem cells (LSCs). These cells have been
      described in the CD34 + CD38- cell fraction. Leukapheresis products were
      harvested in 123 patients in morphological complete remission and analyzed by
      multiparameter flow cytometry. The CD34 + CD38- cell population showed a
      prognostic impact on survival. Median event-free survival (EFS) was 8.2 months (3
      year EFS: 29%) for those with a higher percentage of CD34 + CD38- versus 91.9
      months (3-year EFS: 62%) for those with a lower percentage for the entire cohort.
      These differences were confirmed in patients undergoing autologous stem cell
      transplant, with median EFS of 7.3 months versus 91.1 months (3-year EFS: 31% vs.
      70%). Higher proportions of CD34 + CD38- cells were associated with adverse
      cytogenetics and with earlier relapses. Higher percentages of CD34 + CD38- cells
      in apheresis products reflect inadequate in vivo purging and reliably distinguish
      samples enriched in LSCs from those involving mainly normal cells. 

PMID- 24884315
TI  - Outcomes of chronic-phase chronic myeloid leukemia beyond first-line therapy.
AB  - The therapeutic landscape of chronic-phase chronic myeloid leukemia (CP-CML) has
      truly been revolutionized with the advent of BCR-ABL1 tyrosine-kinase inhibitor
      (TKI) therapy. First-line therapy with the TKI imatinib has produced high rates
      of remissions among treatment-naive patients, as well as patients previously
      treated with interferon. However, imatinib resistance and intolerance remain
      significant clinical challenges. Dasatinib, nilotinib, bosutinib and ponatinib
      are more recently developed TKIs that have been shown to be very effective as
      second- or later-line treatment for CML after imatinib failure. Dasatinib and
      nilotinib are also approved for use in newly diagnosed patients with CP-CML, and
      produce faster responses when compared with first-line imatinib. Resistance or
      intolerance can occur with any of the currently available TKIs, necessitating a
      change to an alternative TKI or consideration of allogeneic hematopoietic stem
      cell transplant. Treatment options and outcomes for patients whose first-line
      therapy has failed are reviewed in depth in this article. 

PMID- 24884316
TI  - Alternative intensive induction chemotherapeutic regimens in MYC expressing
      diffuse large B-cell lymphoma.

PMID- 24884317
TI  - Clinical manifestation and prognostic factors of 32 Japanese patients with
      autoimmune disease-associated diffuse large B-cell lymphoma.

PMID- 24884318
TI  - Cryptotanshinone acts synergistically with imatinib to induce apoptosis of human
      chronic myeloid leukemia cells.
AB  - Imatinib resistance has emerged as a significant clinical problem in chronic
      myeloid leukemia (CML) treatment. In this study, we investigated the effect and
      mechanism of combination treatment with imatinib and cryptotanshinone (CPT) in
      CML cells. Cotreatment with imatinib and CPT showed a significant synergistic
      killing effect in both imatinib sensitive and resistant CML cell lines, as well
      as primary CML cells. Furthermore, combination treatment induced apoptosis
      significantly, as indicated by increases in apoptotic cell fraction and
      activities of proapoptotic proteins. Subsequent studies revealed that CPT
      significantly inhibited Bcr/Abl protein expression, as well as phosphorylation
      expression levels of signal transducer and activator of transcription 3 (STAT3),
      mammalian target of rapamycin (mTOR) and eukaryotic translation initiation factor
      4E (eIF4E), which are critical mediators of Bcr/Abl transformation. Furthermore,
      CPT in combination with imatinib dramatically decreased the activity of the
      Bcr/Abl pathway in both K562 and K562-R cells. Our results demonstrated that CPT
      increased imatinib-induced apoptosis in a Bcr/Abl dependent manner, suggesting a
      novel strategy for the treatment of CML. 

PMID- 24884319
TI  - Bendamustine for the treatment of multiple myeloma in first-line and relapsed
      refractory settings: a review of clinical trial data.
AB  - Multiple myeloma (MM) is a hematologic malignancy characterized by abnormal
      growth and/or dysregulation of plasma cells leading to the build-up of malignant
      plasma cells in the bone marrow and increased production of monoclonal
      immunoglobulins. Treatment modalities for MM include autologous stem cell
      transplant (ASCT), chemotherapy with conventional and immunomodulatory agents,
      radiation therapy and adjunct therapies. Bendamustine is a synthetic
      chemotherapeutic agent combining the alkylating properties of a mustard group
      with the activities of a benzimidazole ring, giving it a unique alkylating
      activity compared with other alkylating agents. Bendamustine has proven activity
      in both newly diagnosed and relapsed-refractory MM. Bendamustine has also
      demonstrated activity in MM after relapse from ASCT, and has recently been used
      successfully as a conditioning regimen for ASCT in combination with melphalan.
      Bendamustine is generally well tolerated, with the majority of adverse events
      being due to bone marrow suppression. Extramedullary toxicity is infrequent and
      usually mild. 

PMID- 24884320
TI  - Lenalidomide (Revlimid), bortezomib (Velcade) and dexamethasone for the treatment
      of secondary plasma cell leukemia.

PMID- 24884326
TI  - What's NEW in the New Year at JPN.

PMID- 24884328
TI  - Surface adsorption and bulk aggregation of cyclodextrins by computational
      molecular dynamics simulations as a function of temperature: alpha-CD vs beta-CD.
AB  - The structural simplicity of native cyclodextrins (CDs) contrasts with their
      complex behavior in the bulk of aqueous solutions, mainly when they are combined
      with other cosolutes. Many scientific and industrial applications based on these
      molecules are supported only by empirical information. The lack of fundamental
      knowledge, which would allow one to rationally optimize many of these
      applications, is notable mainly at the solution/air interface. Basic information
      on phenomena such as the spontaneous adsorption of native CDs or on the structure
      of CD aggregates in the bulk solution is really scarce. In order to fill these
      gaps, a detailed computational study on the adsorption and aggregation of alpha-
      and beta-CDs as a function of temperature is presented here. Our simulations
      reproduce, at atomic resolution, the experimentally observed much higher ability
      of beta-CD to aggregate compared to that of alpha-CD at 298 K, as well as their
      dependence on temperature. The adsorption of both individual CDs and small CD
      aggregates (up to 20 molecules) to the solution/air interface is found to be
      negligible. 0.8 MUs long trajectories of single CD molecules in aqueous solution
      reveal that the main differences in the behavior of both CDs are their
      flexibility, higher for beta-CD, and the occupancy of individual intramolecular
      hydrogen bonds that is significantly longer for the same cyclodextrin. The
      aggregation pattern of alpha- and beta-CDs is followed at the hundreds of ns time
      scale, allowing both the spontaneous self-assembly of cyclodextrins and their
      redistribution along the aggregates to be observed. This is the first attempt to
      study the adsorption and aggregation of native cyclodextrins by atomistic
      molecular dynamics simulations. 

PMID- 24884333
TI  - Field testing the alternative criteria for tension-type headache proposed in the
      third beta edition of the international classification of headache disorders:
      results from the Korean headache-sleep study.
AB  - BACKGROUND: According to the third beta edition of the International
      Classification of Headache Disorder (ICHD-3 beta), the diagnostic criteria for
      tension-type headache (TTH) might lead to the inclusion of individuals with
      headaches showing migrainous features. To better define TTH, the alternative
      diagnostic criteria were proposed in the appendix of ICHD-3 beta. This study
      attempted to test the alternative criteria for diagnosis of TTH proposed in ICHD
      3 beta in a population-based sample from Korea. METHODS: We selected participants
      from the Korean population aged 19-69 years using stratified random sampling and
      evaluated them by interview using a questionnaire designed to identify headache
      type, headache characteristics, and psychiatric comorbidities. RESULTS: Of the
      2,762 participants, 586 (21.3%) were diagnosed as having TTH using the standard
      criteria. Among these, 238 (40.6%) were also classified as having TTH using the
      alternative criteria. All 238 TTH subjects first diagnosed as having TTH by the
      alternative criteria were also classified as having TTH by the standard criteria.
      If the standard criteria were not applied, the remaining 348 patients were
      subclassified as having probable migraine (115, 19.6%) and unclassified headache
      (233, 39.7%). Compared with subjects diagnosed with TTH using the standard
      criteria, those diagnosed using the alternative criteria were less likely to
      demonstrate unilateral, pulsating headache, which is aggravated by movement,
      photophobia, phonophobia, and osmophobia. CONCLUSION: Using the alternative
      criteria, less than half of the subjects with TTH according to the standard
      criteria were classified as having TTH. All the subjects with TTH by the
      alternative criteria were classified as having TTH by the standard criteria. This
      study also demonstrated that subjects diagnosed with TTH using the standard
      criteria could include people with headaches showing migrainous features.

PMID- 24884339
TI  - Photothermoelectric and photoelectric contributions to light detection in metal
      graphene-metal photodetectors.
AB  - Graphene's high mobility and Fermi velocity, combined with its constant light
      absorption in the visible to far-infrared range, make it an ideal material to
      fabricate high-speed and ultrabroadband photodetectors. However, the precise
      mechanism of photodetection is still debated. Here, we report wavelength and
      polarization-dependent measurements of metal-graphene-metal photodetectors. This
      allows us to quantify and control the relative contributions of both photothermo-
      and photoelectric effects, both adding to the overall photoresponse. This paves
      the way for a more efficient photodetector design for ultrafast operating speeds.

PMID- 24884338
TI  - Phospholipase A/Acyltransferase enzyme activity of H-rev107 inhibits the H-RAS
      signaling pathway.
AB  - BACKGROUND: H-rev107, also called HRASLS3 or PLA2G16, is a member of the HREV107
      type II tumor suppressor gene family. Previous studies showed that H-rev107
      exhibits phospholipase A/acyltransferase (PLA/AT) activity and downregulates H
      RAS expression. However, the mode of action and the site of inhibition of H-RAS
      by H-rev107 are still unknown. RESULTS: Our results indicate that H-rev107 was co
      precipitated with H-RAS and downregulated the levels of activated RAS (RAS-GTP)
      and ELK1-mediated transactivation in epidermal growth factor-stimulated and H-RAS
      cotransfected HtTA cervical cancer cells. Furthermore, an acyl-biotin exchange
      assay demonstrated that H-rev107 reduced H-RAS palmitoylation. H-rev107 has been
      shown to be a PLA/AT that is involved in phospholipid metabolism. Treating cells
      with the PLA/AT inhibitor arachidonyl trifluoromethyl ketone (AACOCF3) or methyl
      arachidonyl fluorophosphate (MAFP) alleviated H-rev107-induced downregulation of
      the levels of acylated H-RAS. AACOCF3 and MAFP also increased activated RAS and
      ELK1-mediated transactivation in H-rev107-expressing HtTA cells following their
      treatment with epidermal growth factor. In contrast, treating cells with the acyl
      protein thioesterase inhibitor palmostatin B enhanced H-rev107-mediated
      downregulation of acylated H-RAS in H-rev107-expressing cells. Palmostatin B had
      no effect on H-rev107-induced suppression of RAS-GTP levels or ELK1-mediated
      transactivation. These results suggest that H-rev107 decreases H-RAS activity
      through its PLA/AT activity to modulate H-RAS acylation. CONCLUSIONS: We made the
      novel observation that H-rev107 decrease in the steady state levels of H-RAS
      palmitoylation through the phospholipase A/acyltransferase activity. H-rev107 is
      likely to suppress activation of the RAS signaling pathway by reducing the levels
      of palmitoylated H-RAS, which decreases the levels of GTP-bound H-RAS and also
      the activation of downstream molecules. Our study further suggests that the
      PLA/AT activity of H-rev107 may play an important role in H-rev107-mediated RAS
      suppression.

PMID- 24884340
TI  - Experience of affects predicting sense of self and others in short-term dynamic
      and cognitive therapy.
AB  - The present study examined whether levels of activating affects (AA) and
      inhibitory affects (IA) were related to change toward more compassionate and
      realistic levels of sense of self (SoS) and sense of others (SoO). The sample
      included 47 patients diagnosed with cluster C personality disorders, who received
      40 sessions of either cognitive therapy or short-term dynamic therapy (see the
      randomized controlled trial study, Svartberg, Stiles, & Seltzer, 2004). A total
      of 927 videotaped sessions were rated with the use of the observational
      instrument, Achievement of Therapeutic Objectives Scale. Longitudinal multilevel
      modeling enabled the examination of both between-person effects and within-person
      changes in level of AA and IA. Patients with better ability to experience AA at
      the start of therapy displayed significantly higher SoS and SoO across sessions
      compared with other patients. Patients who experienced higher levels of IA at the
      start of therapy displayed lower levels of SoS across sessions. A patient
      experiencing more AA than usual for him/her self within a session predicted an
      increased level of SoS and SoO at the next measuring point. There were no
      different change patterns in the 2 treatment groups. Results suggest that focus
      within therapy sessions on increasing patients' AA can help facilitate change in
      SoS and SoO toward more compassionate and realistic quality.

PMID- 24884343
TI  - Lung clearance index in adults with non-cystic fibrosis bronchiectasis.
AB  - BACKGROUND: Lung clearance index (LCI) is a measure of abnormal ventilation
      distribution derived from the multiple breath inert gas washout (MBW) technique.
      We aimed to determine the clinical utility of LCI in non-CF bronchiectasis, and
      to assess two novel MBW parameters that distinguish between increases in LCI due
      to specific ventilation inequality (LCIvent) and increased respiratory dead space
      (LCIds). METHODS: Forty-three patients with non-CF bronchiectasis and 18 healthy
      control subjects underwent MBW using the sulphur hexafluoride wash-in technique,
      and data from 40 adults with CF were re-analysed. LCIvent and LCIds were
      calculated using a theoretical two-compartment lung model, and represent the
      proportional increase in LCI above its ideal value due to specific ventilation
      inequality and increased respiratory dead space, respectively. RESULTS: LCI was
      significantly raised in patients with non-CF bronchiectasis compared to healthy
      controls (9.99 versus 7.28, p < 0.01), and discriminated well between these two
      groups (area under receiver operating curve = 0.90, versus 0.83 for forced
      expiratory volume in one second [% predicted]). LCI, LCIvent and LCIds were
      repeatable (intraclass correlation coefficient > 0.75), and correlated
      significantly with measures of spirometric airflow obstruction. CONCLUSION: LCI
      is repeatable, discriminatory, and is associated with spirometric airflow
      obstruction in patients with non-CF bronchiectasis. LCIvent and LCIds are a
      practical and repeatable alternative to phase III slope analysis and may allow a
      further level of mechanistic information to be extracted from the MBW test in
      patients with severe ventilation heterogeneity.

PMID- 24884347
TI  - Test of mindfulness and hope components in a psychological intervention for women
      with cancer recurrence.
AB  - OBJECTIVE: Psychological interventions can attenuate distress and enhance coping
      for those with an initial diagnosis of cancer, but there are few intervention
      options for individuals with cancer recurrence. To address this gap, we developed
      and tested a novel treatment combining Mindfulness, Hope Therapy, and
      biobehavioral components. METHOD: An uncontrolled, repeated measures design was
      used. Women (N = 32) with recurrent breast or gynecologic cancers were provided
      20 treatment sessions in individual (n = 12) or group (n = 20) formats. On
      average, participants were middle aged (M = 58) and Caucasian (81%). Independent
      variables (i.e., hope and mindfulness) and psychological outcomes (i.e.,
      depression, negative mood, worry, and symptoms of generalized anxiety disorder)
      were assessed pre-treatment and 2, 4, and 7 months later. Session-by-session
      therapy process (positive and negative affect, quality-of-life) and mechanism
      (use of intervention-specific skills) measures were also included. RESULTS:
      Distress, anxiety, and negative affect decreased, whereas positive affect and
      mental-health-related quality-of-life increased over the course of treatment, as
      demonstrated in mixed-effects models with the intent-to-treat sample. Both hope
      and mindfulness increased, and use of mindfulness skills was related to decreased
      anxiety. CONCLUSIONS: This treatment was feasible to deliver and was acceptable
      to patients. The trial serves as preliminary evidence for a multi-component
      intervention tailored to treat difficulties specific to recurrent cancer. The
      blending of the components was novel as well as theoretically and practically
      consistent. A gap in the literature is addressed, providing directions for
      testing interventions designed for patients coping with the continuing stressors
      and challenges of cancer recurrence.

PMID- 24884350
TI  - Subdural haemorrhage is associated with recent morphine treatment in patients
      with cancer: a retrospective population-based nested case-control study.
AB  - BACKGROUND: This study investigated the relationship between recent morphine use
      and risk of subdural haemorrhage (SDH) in patients with cancer. METHODS: This
      study identified a malignancy cohort of 25,322 patients who had never received
      morphine treatment. In this malignancy cohort, 200 patients who subsequently
      developed SDH were designated as the SDH group. Control-group patients without
      SDH were selected from the malignancy cohort and were matched ~4:1 to each SDH
      case for age, sex, year of cancer diagnosis and index year. Morphine use was
      designated as 'recent' if the prescription duration covered the index date or
      ended within 6 months before the index date. Logistic regression was used to
      estimate odds ratios and 95% confidence intervals and a multivariable model was
      applied to control for age, sex and cerebrovascular disease. RESULTS: Compared
      with non-morphine users, patients with cancer who received morphine within 6
      months of the index date exhibited a 2.58-fold (95% CI = 1.23-5.39) increase in
      the risk of developing SDH. The risk of SDH development increased as the duration
      of morphine treatment increased. CONCLUSION: The incidence of SDH in patients
      with cancer in Taiwan is associated with recent morphine treatment (<=6 months)
      and is dependent on the duration of morphine use.

PMID- 24884349
TI  - A predictor for predicting Escherichia coli transcriptome and the effects of gene
      perturbations.
AB  - BACKGROUND: A means to predict the effects of gene over-expression, knockouts,
      and environmental stimuli in silico is useful for system biologists to develop
      and test hypotheses. Several studies had predicted the expression of all
      Escherichia coli genes from sequences and reported a correlation of 0.301 between
      predicted and actual expression. However, these do not allow biologists to study
      the effects of gene perturbations on the native transcriptome. RESULTS: We
      developed a predictor to predict transcriptome-scale gene expression from a small
      number (n = 59) of known gene expressions using gene co-expression network, which
      can be used to predict the effects of over-expressions and knockdowns on E. coli
      transcriptome. In terms of transcriptome prediction, our results show that the
      correlation between predicted and actual expression value is 0.467, which is
      similar to the microarray intra-array variation (p-value = 0.348), suggesting
      that intra-array variation accounts for a substantial portion of the
      transcriptome prediction error. In terms of predicting the effects of gene
      perturbation(s), our results suggest that the expression of 83% of the genes
      affected by perturbation can be predicted within 40% of error and the correlation
      between predicted and actual expression values among the affected genes to be
      0.698. With the ability to predict the effects of gene perturbations, we
      demonstrated that our predictor has the potential to estimate the effects of
      varying gene expression level on the native transcriptome. CONCLUSION: We present
      a potential means to predict an entire transcriptome and a tool to estimate the
      effects of gene perturbations for E. coli, which will aid biologists in
      hypothesis development. This study forms the baseline for future work in using
      gene co-expression network for gene expression prediction.

PMID- 24884351
TI  - Menopausal symptoms and quality of life in Turkish women in the climacteric
      period.
AB  - OBJECTIVES: The purpose of this study is to determine the frequency of menopausal
      symptoms in Turkish women and the impact of these symptoms and related factors on
      the quality of life. METHODS: The sample in this cross-sectional study consisted
      of 1030 women, aged 40-59 years. The researcher collected the data at the women's
      homes via the face-to-face interview method using the Menopause-Specific Quality
      of Life (MENQOL) questionnaire and a questionnaire developed and drawn up in line
      with the literature. RESULTS: The mean age (+/- standard deviation) of the women
      participating in the study was 48.58 +/- 5.61 years and their mean menopausal age
      was 46.4 +/- 4.4 years. While the most frequently experienced menopausal symptoms
      in the study were feeling tired and worn out (79.2%), aches in the muscles and
      joints (79.1%) and low backache (77.8%), the least experienced symptom was an
      increase in facial hair (28.3%). Significant differences were found between the
      subdomain mean scores on the MENQOL according to menopausal periods (p = 0.000).
      Significant differences were detected in all subdomain mean scores of the MENQOL
      questionnaire according to age groups, perception of income, education, parity
      and body mass index (p < 0.05). CONCLUSION: In women in the climacteric period,
      the time that quality of life is the most affected among all the menopausal
      periods is the postmenopausal period. Women in menopause should not be forgotten;
      health-care services addressing the health needs of women should not be
      restricted only to the period of fertility but continued with the same
      sensitivity throughout the life cycle.

PMID- 24884352
TI  - Identifying crash patterns on roundabouts.
AB  - OBJECTIVES: Roundabouts are a type of circular intersection control generally
      associated with a favorable influence on traffic safety. International studies of
      intersections converted to roundabouts indicate a strong reduction in injury
      crashes, particularly for crashes with fatal or serious injuries. Nevertheless,
      some crashes still occur at roundabouts. The present study aims to improve the
      understanding of roundabout safety by identifying crash types, locations, and
      factors that are associated with roundabout crashes. METHODS: An analysis of 399
      crashes on 28 roundabouts in Flanders, Belgium, was carried out based on detailed
      crash descriptions; that is, crash data and collision diagrams. The crashes are
      sampled from police-reported crashes at roundabouts in the region of Flanders,
      Belgium. Collision diagrams of the registered crashes were used to distinguish 8
      different crash types. The roundabout itself is divided into 11 detailed and
      different typical segments, according to previously established knowledge on the
      occurrence of crashes at roundabouts. The 8 roundabout crash types are examined
      by injury severity, crash location within the roundabout, type of roundabout,
      type of cycle facility, and type of involved road user. RESULTS: Four dominant
      crash types are identified: rear-end crashes, collisions with vulnerable road
      users, entering-circulating crashes, and single-vehicle collisions with the
      central island. Crashes with vulnerable road users and collisions with the
      central island are characterized by significantly higher proportions of injury
      crashes. About 80% of the crashes occurred on the entry lanes and the circulatory
      road (segments 1-4). Road users who are the most at risk to be involved in
      serious injury crashes at roundabouts are cyclists and moped riders. CONCLUSIONS:
      The main goal of this study was to identify and analyze dominant crash types at
      roundabouts by taking into account detailed information on the crash location.
      Some connections between certain roundabout crash types, their crash location,
      and roundabout design characteristics have been found.

PMID- 24884353
TI  - The relation between stress and sexual function and satisfaction in reproductive
      age women in Iran: a cross-sectional study.
AB  - The present study aimed to evaluate the relation between stress and different
      aspects of female sexual function and satisfaction. This cross-sectional study
      was conducted on 228 reproductive-age women who were referred to the public
      Health Centers in Ahvaz, Iran. All eligible participants were asked to complete a
      demographic questionnaire, the Female Sexual Function Index, and the Perceived
      Stress Scale. The data were analyzed using independent t test, Pearson
      correlation, and logistic regression. The mean score of stress was 32.9 (SD =
      4.7) in the normal sexual function group and 33.3 (SD = 5.5) in the unfavorable
      sexual function group. There was a significant correlation between stress and
      sexual function score, sexual desire, arousal, orgasm, lubrication, sexual pain,
      and satisfaction (p <.001). Spouses' education (OR = 0.15, CI [0.02, 0.97], p
      =.04) and frequency of sexual intercourse per week (OR = 1.8, CI [1.3, 2.5], p
      <.001) had a significant relation with stress. There is a significant relation
      between women's perceived stress and sexual function and satisfaction. Further
      analytical studies are needed to show the harmful effects of stress on women's
      sexual activity and satisfaction. 

PMID- 24884357
TI  - Enhanced production of functional extracellular single chain variable fragment
      against HIV-1 matrix protein from Escherichia coli by sequential simplex
      optimization.
AB  - The optimal culture condition for extracellular recombinant single chain variable
      fragment anti HIV-1 p17 protein (scFv anti-p17) production in Escherichia coli
      HB2151 was investigated by the sequential simplex optimization (SS) method. Five
      variable parameters were submitted in the fermentation process. The most
      favorable condition obtained from 19 independent experiments was as followed: 58
      uM of IPTG induction to 1.7 OD600 nm at 25.5 degrees C for 16 h with 202 rpm
      agitation rate. The amount of secreted scFv anti-p17 at the optimal condition was
      38% higher than under the control condition. The binding activity of soluble
      extracellular scFv anti-p17 protein increased 95.5% and 73.2% in comparison with
      the control condition and non-optimized condition respectively. The soluble scFv
      anti-p17 from crude HB2151 lysated was subsequently purified by immobilized metal
      ion affinity chromatography (IMAC) with His-tag. The purified scFv anti-p17 was
      intact and retained its antigen-binding affinity against HIV-1 p17. We
      demonstrated that the sequential simplex optimization method was a key for
      exertion of high yield with fewer experimental requirements for acquiring of
      large scale secretory protein production. 

PMID- 24884355
TI  - Toona sinensis leaf extract inhibits lipid accumulation through up-regulation of
      genes involved in lipolysis and fatty acid oxidation in adipocytes.
AB  - Toona sinensis leaf (TSL) has been shown to lower plasma triacylglycerol levels
      and diminish the size of visceral fat cells in vivo. The molecular mechanism of
      TSL ethanol extract (TSL-E) on lipid metabolism in 3T3-L1 adipocytes was
      investigated in this study. Oil Red O staining as well as immunoblotting, real
      time PCR, and dual-Luciferase reporter system were performed to investigate the
      effect of TSL-E on lipid accumulation and the regulation of lipid metabolism,
      respectively. In addition, active compounds in the TSL-E were analyzed by HPLC.
      TSL-E significantly decreased lipid accumulation, stimulated free fatty acid
      (FFA) release, and up-regulated peroxisome proliferator-activated receptor-alpha
      (PPARalpha) and genes involved in peroxisomal (acyl-CoA oxidase) and
      mitochondrial (uncouple protein 3) fatty acid oxidation. TSL-E also up-regulated
      cytoplasmic triacylglycerol hydrolysis gene (adipose triglyceride lipase) and
      genes related to fatty acid oxidation (AMP-activated protein kinase, acetyl-CoA
      carboxylase, carnitine palmitoyltransferase I, PPARgamma, and adiponectin). The
      major constituents directly inducing PPARalpha transactivity in TSL-E are gallic
      acid, rutin, palmitic acid, linoleic acid, and alpha-linolenic acid. These
      results indicate that the inhibitory effect of TSL-E on lipid accumulation was
      through PPARalpha activation and further up-regulation of PPARalpha-mediated
      genes plus up-regulation of cytoplasmic genes involved in lipid catabolism. 

PMID- 24884358
TI  - A resource-saving collective approach to biomedical semantic role labeling.
AB  - BACKGROUND: Biomedical semantic role labeling (BioSRL) is a natural language
      processing technique that identifies the semantic roles of the words or phrases
      in sentences describing biological processes and expresses them as predicate
      argument structures (PAS's). Currently, a major problem of BioSRL is that most
      systems label every node in a full parse tree independently; however, some nodes
      always exhibit dependency. In general SRL, collective approaches based on the
      Markov logic network (MLN) model have been successful in dealing with this
      problem. However, in BioSRL such an approach has not been attempted because it
      would require more training data to recognize the more specialized and diverse
      terms found in biomedical literature, increasing training time and computational
      complexity. RESULTS: We first constructed a collective BioSRL system based on
      MLN. This system, called collective BIOSMILE (CBIOSMILE), is trained on the
      BioProp corpus. To reduce the resources used in BioSRL training, we employ a tree
      pruning filter to remove unlikely nodes from the parse tree and four argument
      candidate identifiers to retain candidate nodes in the tree. Nodes not recognized
      by any candidate identifier are discarded. The pruned annotated parse trees are
      used to train a resource-saving MLN-based system, which is referred to as
      resource-saving collective BIOSMILE (RCBIOSMILE). Our experimental results show
      that our proposed CBIOSMILE system outperforms BIOSMILE, which is the top BioSRL
      system. Furthermore, our proposed RCBIOSMILE maintains the same level of accuracy
      as CBIOSMILE using 92% less memory and 57% less training time. CONCLUSIONS: This
      greatly improved efficiency makes RCBIOSMILE potentially suitable for training on
      much larger BioSRL corpora over more biomedical domains. Compared to real-world
      biomedical corpora, BioProp is relatively small, containing only 445 MEDLINE
      abstracts and 30 event triggers. It is not large enough for practical
      applications, such as pathway construction. We consider it of primary importance
      to pursue SRL training on large corpora in the future.

PMID- 24884360
TI  - Molecular evolution and functional characterisation of an ancient phenylalanine
      ammonia-lyase gene (NnPAL1) from Nelumbo nucifera: novel insight into the
      evolution of the PAL family in angiosperms.
AB  - BACKGROUND: Phenylalanine ammonia-lyase (PAL; E.C.4.3.1.5) is a key enzyme of the
      phenylpropanoid pathway in plant development, and it catalyses the deamination of
      phenylalanine to trans-cinnamic acid, leading to the production of secondary
      metabolites. This enzyme has been identified in many organisms, ranging from
      prokaryotes to higher plants. Because Nelumbo nucifera is a basal dicot rich in
      many secondary metabolites, it is a suitable candidate for research on the
      phenylpropanoid pathway. RESULTS: Three PAL members, NnPAL1, NnPAL2 and NnPAL3,
      have been identified in N. nucifera using genome-wide analysis. NnPAL1 contains
      two introns; however, both NnPAL2 and NnPAL3 have only one intron. Molecular and
      evolutionary analysis of NnPAL1 confirms that it is an ancient PAL member of the
      angiosperms and may have a different origin. However, PAL clusters, except
      NnPAL1, are monophyletic after the split between dicots and monocots. These
      observations suggest that duplication events remain an important occurrence in
      the evolution of the PAL gene family. Molecular assays demonstrate that the mRNA
      of the NnPAL1 gene is 2343 bp in size and encodes a 717 amino acid polypeptide.
      The optimal pH and temperature of the recombinant NnPAL1 protein are 9.0 and 55
      degrees C, respectively. The NnPAL1 protein retains both PAL and weak TAL
      catalytic activities with Km values of 1.07 mM for L-phenylalanine and 3.43 mM
      for L-tyrosine, respectively. Cis-elements response to environmental stress are
      identified and confirmed using real-time PCR for treatments with abscisic acid
      (ABA), indoleacetic acid (IAA), ultraviolet light, Neurospora crassa (fungi) and
      drought. CONCLUSIONS: We conclude that the angiosperm PAL genes are not derived
      from a single gene in an ancestral angiosperm genome; therefore, there may be
      another ancestral duplication and vertical inheritance from the gymnosperms. The
      different evolutionary histories for PAL genes in angiosperms suggest different
      mechanisms of functional regulation. The expression patterns of NnPAL1 in
      response to stress may be necessary for the survival of N. nucifera since the
      Cretaceous Period. The discovery and characterisation of the ancient NnPAL1 help
      to elucidate PAL evolution in angiosperms.

PMID- 24884361
TI  - Hemiclonal analysis of interacting phenotypes in male and female Drosophila
      melanogaster.
AB  - BACKGROUND: Identifying the sources of variation in mating interactions between
      males and females is important because this variation influences the strength
      and/or the direction of sexual selection that populations experience. While the
      origins and effects of variation in male attractiveness and ornamentation have
      received much scrutiny, the causes and consequences of intraspecific variation in
      females have been relatively overlooked. We used cytogenetic cloning techniques
      developed for Drosophila melanogaster to create "hemiclonal" males and females
      with whom we directly observed sexual interaction between individuals of
      different known genetic backgrounds and measured subsequent reproductive
      outcomes. Using this approach, we were able to quantify the genetic contribution
      of each mate to the observed phenotypic variation in biologically important
      traits including mating speed, copulation duration, and subsequent offspring
      production, as well as measure the magnitude and direction of intersexual genetic
      correlation between female choosiness and male attractiveness. RESULTS: We found
      significant additive genetic variation contributing to mating speed that can be
      attributed to male genetic identity, female genetic identity, but not their
      interaction. Furthermore we found that phenotypic variation in copulation
      duration had a significant male-associated genetic component. Female genetic
      identity and the interaction between male and female genetic identity accounted
      for a substantial amount of the observed phenotypic variation in egg size.
      Although previous research predicts a trade-off between egg size and fecundity,
      this was not evident in our results. We found a strong negative genetic
      correlation between female choosiness and male attractiveness, a result that
      suggests a potentially important role for sexually antagonistic alleles in sexual
      selection processes in our population. CONCLUSION: These results further our
      understanding of sexual selection because they identify that genetic identity
      plays a significant role in phenotypic variation in female behaviour and
      fecundity. This variation may be potentially due to ongoing sexual conflict found
      between the sexes for interacting phenotypes. Our unexpected observation of a
      negative correlation between female choosiness and male attractiveness highlights
      the need for more explicit theoretical models of genetic covariance to
      investigate the coevolution of female choosiness and male attractiveness.

PMID- 24884362
TI  - The link between transcript regulation and de novo protein synthesis in the
      retrograde high light acclimation response of Arabidopsis thaliana.
AB  - BACKGROUND: Efficient light acclimation of photosynthetic cells is a basic and
      important property of plants. The process of acclimation depends on
      transformation of retrograde signals in gene expression, transcript accumulation
      and de novo protein synthesis. While signalling cues, transcriptomes and some
      involved players have been characterized, an integrated view is only slowly
      emerging, and information on the translational level is missing. Transfer of low
      (8 MUmol quanta.m(-2).s(-1)) or normal light (80 MUmol quanta.m(-2).s(-1))
      acclimated 30 d old Arabidopsis thaliana plants to high light (800 MUmol
      quanta.m(-2).s(-1)) triggers retrograde signals. Using this established approach,
      we sought to link transcriptome data with de novo synthesized proteins by in vivo
      labelling with (35)S methionine and proteome composition. RESULTS: De novo
      synthesized protein and proteome patterns could reliably be matched with newly
      annotated master gels. Each molecular level could be quantified for a set of 41
      proteins. Among the proteins preferentially synthesized in plants transferred to
      high light were enzymes including carbonic anhydrase, fructose-1,6-bisphosphate
      aldolase, O-acetyl serine thiol lyase, and chaperones, while low rates upon
      transfer to high light were measured for e.g. dehydroascorbate reductase,
      glyceraldehyde-3-phosphate dehydrogenase and CuZn superoxide dismutase, and
      opposite responses between 10-fold and 100-fold light increment for e.g.
      glutamine synthetase and phosphoglycerate kinase. CONCLUSIONS: The results prove
      the hypothesis that transcript abundance is poorly linked to de novo protein
      synthesis due to profound regulation at the level of translation. This vertical
      systems biology approach enables to quantitatively and kinetically link the
      molecular levels for scrutinizing signal processing and response generation.

PMID- 24884364
TI  - The wide expansion of hepatitis delta virus-like ribozymes throughout
      trypanosomatid genomes is linked to the spreading of L1Tc/ingi clade mobile
      elements.
AB  - BACKGROUND: Hepatitis Delta Virus (HDV)-like ribozymes have recently been found
      in many mobile elements in which they take part in a mechanism that releases
      intermediate RNAs from cellular co-transcripts. L1Tc in Trypanosoma cruzi is one
      of the elements in which such a ribozyme is located. It lies in the so-called
      Pr77-hallmark, a conserved region shared by retrotransposons belonging to the
      trypanosomatid L1Tc/ingi clade. The wide distribution of the Pr77-hallmark
      detected in trypanosomatid retrotransposons renders the potential catalytic
      activity of these elements worthy of study: their distribution might contribute
      to host genetic regulation at the mRNA level. Indeed, in Leishmania spp, the
      pervasive presence of these HDV-like ribozyme-containing mobile elements in
      certain 3'-untranslated regions of protein-coding genes has been linked to mRNA
      downregulation. RESULTS: Intensive screening of publicly available trypanosomatid
      genomes, combined with manual folding analyses, allowed the isolation of
      putatively Pr77-hallmarks with HDV-like ribozyme activity. This work describes
      the conservation of an HDV-like ribozyme structure in the Pr77 sequence of
      retrotransposons in a wide range of trypanosomatids, the catalytic function of
      which is maintained in the majority.These results are consistent with the
      previously suggested common phylogenetic origin of the elements that belong to
      this clade, although in some cases loss of functionality appears to have occurred
      and/or perhaps molecular domestication by the host. CONCLUSIONS: These HDV-like
      ribozymes are widely distributed within retrotransposons across trypanosomatid
      genomes. This type of ribozyme was once thought to be rare in nature, but in fact
      it would seem to be abundant in trypanosomatid transcripts. It can even form part
      of the pool of mRNA 3'-untranslated regions, particularly in Leishmania spp. Its
      putative regulatory role in host genetic expression is discussed.

PMID- 24884369
TI  - Regression hidden Markov modeling reveals heterogeneous gene expression
      regulation: a case study in mouse embryonic stem cells.
AB  - BACKGROUND: Studies have shown the strong association between histone
      modification levels and gene expression levels. The detailed relationships
      between the two can vary substantially due to differential regulation, and hence
      a simple regression model may not be adequate. We apply a regression hidden
      Markov model (regHMM) to further investigate the potential multiple relationships
      between genes and histone methylation levels in mouse embryonic stem cells.
      RESULTS: Seven histone methylation levels are used in the study. Averaged histone
      modifications over non-overlapping 200 bp windows on the range transcription
      starting site (TSS) +/- 1 Kb are used as predictors, and in total 70 explanatory
      variables are generated. Based on regHMM results, genes segregated into two
      groups, referred to as State 1 and State 2, have distinct association strengths.
      Genes in State 1 are better explained by histone methylation levels with R(2)=.72
      while those in State 2 have weaker association strength with R(2)=.38. The
      regression coefficients in the two states are not very different in magnitude
      except in the intercept,.25 and 1.15 for State 1 and State 2, respectively. We
      found specific GO categories that may be attributed to the different
      relationships. The GO categories more frequently observed in State 2 match those
      of housekeeping genes, such as cytoplasm, nucleus, and protein binding. In
      addition, the housekeeping gene expression levels are significantly less
      explained by histone methylation in mouse embryonic stem cells, which is
      consistent with the constitutive expression patterns that would be expected.
      CONCLUSION: Gene expression levels are not universally affected by histone
      methylation levels, and the relationships between the two differ by the gene
      functions. The expression levels of the genes that perform the most common
      housekeeping genes' GO categories are less strongly associated with histone
      methylation levels. We suspect that additional biological factors may also be
      strongly associated with the gene expression levels in State 2. We discover that
      the effect of the presence of CpG island in TSS +/- 1 Kb is larger in State 2.

PMID- 24884370
TI  - EPAS1 gene variants are associated with sprint/power athletic performance in two
      cohorts of European athletes.
AB  - BACKGROUND: The endothelial PAS domain protein 1 (EPAS1) activates genes that are
      involved in erythropoiesis and angiogenesis, thus favoring a better delivery of
      oxygen to the tissues and is a plausible candidate to influence athletic
      performance. Using innovative statistical methods we compared genotype
      distributions and interactions of EPAS1 SNPs rs1867785, rs11689011, rs895436,
      rs4035887 and rs1867782 between sprint/power athletes (n=338), endurance athletes
      (n=254), and controls (603) in Polish and Russian samples. We also examined the
      association between these SNPs and the athletes' competition level ('elite' and
      'sub-elite' level). Genotyping was performed by either Real-Time PCR or by Single
      Base Extension (SBE) method. RESULTS: In the pooled cohort of Polish and Russian
      athletes, 1) rs1867785 was associated with sprint/power athletic status; the AA
      genotype in rs1867785 was underrepresented in the sprint/power athletes, 2)
      rs11689011 was also associated with sprint/power athletic status; the TT genotype
      in rs11689011 was underrepresented sprint/power athletes, and 3) the interaction
      between rs1867785, rs11689011, and rs4035887 was associated with sprint/power
      athletic performance; the combinations of the AA genotype in rs4035887 with
      either the AG or GG genotypes in rs1867785, or with the CT or CC genotypes in
      rs11689011, were underrepresented in two cohorts of sprint/power athletes.
      CONCLUSIONS: Based on the unique statistical model rs1867785/rs11689011 are
      strong predictors of sprint/power athletic status, and the interaction between
      rs1867785, rs11689011, and rs4035887 might contribute to success in sprint/power
      athletic performance.

PMID- 24884371
TI  - RNA sequencing on Solanum lycopersicum trichomes identifies transcription factors
      that activate terpene synthase promoters.
AB  - BACKGROUND: Glandular trichomes are production and storage organs of specialized
      metabolites such as terpenes, which play a role in the plant's defense system.
      The present study aimed to shed light on the regulation of terpene biosynthesis
      in Solanum lycopersicum trichomes by identification of transcription factors
      (TFs) that control the expression of terpene synthases. RESULTS: A trichome
      transcriptome database was created with a total of 27,195 contigs that contained
      743 annotated TFs. Furthermore a quantitative expression database was obtained of
      jasmonic acid-treated trichomes. Sixteen candidate TFs were selected for further
      analysis. One TF of the MYC bHLH class and one of the WRKY class were able to
      transiently transactivate S. lycopersicum terpene synthase promoters in Nicotiana
      benthamiana leaves. Strikingly, SlMYC1 was shown to act synergistically with a
      previously identified zinc finger-like TF, Expression of Terpenoids 1 (SlEOT1) in
      transactivating the SlTPS5 promoter. CONCLUSIONS: High-throughput sequencing of
      tomato stem trichomes led to the discovery of two transcription factors that
      activated several terpene synthase promoters. Our results identified new elements
      of the transcriptional regulation of tomato terpene biosynthesis in trichomes, a
      largely unexplored field.

PMID- 24884372
TI  - Lung involvement at presentation predicts disease activity and permanent organ
      damage at 6, 12 and 24 months follow - up in ANCA - associated vasculitis.
AB  - BACKGROUND: Antineutrophilic cytoplasmic antibody (ANCA)-associated vasculitis
      (AAV) may present with pulmonary involvement ranging from mild to life
      threatening disease such as diffuse alveolar hemorrhage. There is a paucity of
      information regarding morbidity outcomes for AAV subjects presenting with lung
      involvement. This study determines the relationship between disease activity and
      damage in these subjects using the Birmingham Vasculitis Activity Score v 3 (BVAS
      3) and Vasculitis Damage Index (VDI) respectively. RESULTS: 151 patients with AAV
      were included with 59 presenting initially with pulmonary involvement. The
      initial BVAS scores recorded at time of diagnosis were positively correlated with
      the final VDI scores at 24 months (p < 0.0001, rs = 0.5871). No differences
      between BVAS and VDI scores were seen for both groups, however in the lung
      involvement group only, BVAS scores were significantly higher at 6, 12 and 24
      months whilst the VDI scores were significantly higher at 12 and 24 months.
      Subjects presenting with pulmonary involvement had an increased likelihood for
      cardiovascular (OR 1.31, 95% CI 0.89, 1.54; p = 0.032) and renal (OR 1.32, 95% CI
      1.22, 1.39; p = 0.005) involvement. Subjects presenting with lung involvement
      with granulomatosis with polyangiitis and microscopic polyangiitis had 24-month
      VDI scores that were significantly higher (p = 0.027, p = 0.045), and more likely
      to develop pulmonary fibrosis (OR 1.79, 95% CI 1.48, 2.12; p < 0.001).
      CONCLUSION: AAV subjects with lung involvement at presentation had a higher
      disease activity and damage scores at 6, 12 and 24 months follow-up representing
      a considerable burden of disease despite improvement in overall survival due to
      the introduction of immunosuppressive therapy.

PMID- 24884373
TI  - Boundary cap neural crest stem cells homotopically implanted to the injured
      dorsal root transitional zone give rise to different types of neurons and glia in
      adult rodents.
AB  - BACKGROUND: The boundary cap is a transient group of neural crest-derived cells
      located at the presumptive dorsal root transitional zone (DRTZ) when sensory
      axons enter the spinal cord during development. Later, these cells migrate to
      dorsal root ganglia and differentiate into subtypes of sensory neurons and glia.
      After birth when the DRTZ is established, sensory axons are no longer able to
      enter the spinal cord. Here we explored the fate of mouse boundary cap neural
      crest stem cells (bNCSCs) implanted to the injured DRTZ after dorsal root
      avulsion for their potential to assist sensory axon regeneration. RESULTS:
      Grafted cells showed extensive survival and differentiation after transplantation
      to the avulsed DRTZ. Transplanted cells located outside the spinal cord organized
      elongated tubes of Sox2/GFAP expressing cells closely associated with
      regenerating sensory axons or appeared as small clusters on the surface of the
      spinal cord. Other cells, migrating into the host spinal cord as single cells,
      differentiated to spinal cord neurons with different neurotransmitter
      characteristics, extensive fiber organization, and in some cases surrounded by
      glutamatergic terminal-like profiles. CONCLUSIONS: These findings demonstrate
      that bNCSCs implanted at the site of dorsal root avulsion injury display
      remarkable differentiation plasticity inside the spinal cord and in the
      peripheral compartment where they organize tubes associated with regenerating
      sensory fibers. These properties offer a basis for exploring the ability of
      bNCSCs to assist regeneration of sensory axons into the spinal cord and replace
      lost neurons in the injured spinal cord.

PMID- 24884374
TI  - Extremely elevated room-temperature kinetic isotope effects quantify the critical
      role of barrier width in enzymatic C-H activation.
AB  - The enzyme soybean lipoxygenase (SLO) has served as a prototype for hydrogen
      tunneling reactions, as a result of its unusual kinetic isotope effects (KIEs)
      and their temperature dependencies. Using a synergy of kinetic, structural, and
      theoretical studies, we show how the interplay between donor-acceptor distance
      and active-site flexibility leads to catalytic behavior previously predicted by
      quantum tunneling theory. Modification of the size of two hydrophobic residues by
      site-specific mutagenesis in SLO reduces the reaction rate 10(4)-fold and is
      accompanied by an enormous and unprecedented room-temperature KIE. Fitting of the
      kinetic data to a non-adiabatic model implicates an expansion of the active site
      that cannot be compensated by donor-acceptor distance sampling. A 1.7 A
      resolution X-ray structure of the double mutant further indicates an unaltered
      backbone conformation, almost identical side-chain conformations, and a
      significantly enlarged active-site cavity. These findings show the compelling
      property of room-temperature hydrogen tunneling within a biological context and
      demonstrate the very high sensitivity of such tunneling to barrier width. 

PMID- 24884375
TI  - Multilocus sequence typing and ftsI sequencing: a powerful tool for surveillance
      of penicillin-binding protein 3-mediated beta-lactam resistance in nontypeable
      Haemophilus influenzae.
AB  - BACKGROUND: Beta-lactam resistance in Haemophilus influenzae due to ftsI
      mutations causing altered penicillin-binding protein 3 (PBP3) is increasing
      worldwide. Low-level resistant isolates with the N526K substitution (group II low
      rPBP3) predominate in most geographical regions, while high-level resistant
      isolates with the additional S385T substitution (group III high-rPBP3) are common
      in Japan and South Korea.Knowledge about the molecular epidemiology of rPBP3
      strains is limited. We combined multilocus sequence typing (MLST) and ftsI/PBP3
      typing to study the emergence and spread of rPBP3 in nontypeable H. influenzae
      (NTHi) in Norway. RESULTS: The prevalence of rPBP3 in a population of 795 eye,
      ear and respiratory isolates (99% NTHi) from 2007 was 15%. The prevalence of
      clinical PBP3-mediated resistance to ampicillin was 9%, compared to 2.5% three
      years earlier. Group II low-rPBP3 predominated (96%), with significant
      proportions of isolates non-susceptible to cefotaxime (6%) and meropenem (20%).
      Group III high-rPBP3 was identified for the first time in Northern Europe.Four
      MLST sequence types (ST) with characteristic, highly diverging ftsI alleles
      accounted for 61% of the rPBP3 isolates. The most prevalent substitution pattern
      (PBP3 type A) was present in 41% of rPBP3 isolates, mainly carried by ST367 and
      ST14. Several unrelated STs possessed identical copies of the ftsI allele
      encoding PBP3 type A.Infection sites, age groups, hospitalization rates and rPBP3
      frequencies differed between STs and phylogenetic groups. CONCLUSIONS: This study
      is the first to link ftsI alleles to STs in H. influenzae. The results indicate
      that horizontal gene transfer contributes to the emergence of rPBP3 by phylogeny
      restricted transformation.Clonally related virulent rPBP3 strains are widely
      disseminated and high-level resistant isolates emerge in new geographical
      regions, threatening current empiric antibiotic treatment. The need of continuous
      monitoring of beta-lactam susceptibility and a global system for molecular
      surveillance of rPBP3 strains is underlined. Combining MLST and ftsI/PBP3 typing
      is a powerful tool for this purpose.

PMID- 24884376
TI  - Genome-wide association for grain morphology in synthetic hexaploid wheats using
      digital imaging analysis.
AB  - BACKGROUND: Grain size and shape greatly influence grain weight which ultimately
      enhances grain yield in wheat. Digital imaging (DI) based phenomic
      characterization can capture the three dimensional variation in grain size and
      shape than has hitherto been possible. In this study, we report the results from
      using digital imaging of grain size and shape to understand the relationship
      among different components of this trait, their contribution to enhance grain
      weight, and to identify genomic regions (QTLs) controlling grain morphology using
      genome wide association mapping with high density diversity array technology
      (DArT) and allele-specific markers. RESULTS: Significant positive correlations
      were observed between grain weight and grain size measurements such as grain
      length (r = 0.43), width, thickness (r = 0.64) and factor from density (FFD) (r =
      0.69). A total of 231 synthetic hexaploid wheats (SHWs) were grouped into five
      different sub-clusters by Bayesian structure analysis using unlinked DArT
      markers. Linkage disequilibrium (LD) decay was observed among DArT loci > 10 cM
      distance and approximately 28% marker pairs were in significant LD. In total, 197
      loci over 60 chromosomal regions and 79 loci over 31 chromosomal regions were
      associated with grain morphology by genome wide analysis using general linear
      model (GLM) and mixed linear model (MLM) approaches, respectively. They were
      mainly distributed on homoeologous group 2, 3, 6 and 7 chromosomes. Twenty eight
      marker-trait associations (MTAs) on the D genome chromosomes 2D, 3D and 6D may
      carry novel alleles with potential to enhance grain weight due to the use of
      untapped wild accessions of Aegilops tauschii. Statistical simulations showed
      that favorable alleles for thousand kernel weight (TKW), grain length, width and
      thickness have additive genetic effects. Allelic variations for known genes
      controlling grain size and weight, viz. TaCwi-2A, TaSus-2B, TaCKX6-3D and TaGw2
      6A, were also associated with TKW, grain width and thickness. In silico
      functional analysis predicted a range of biological functions for 32 DArT loci
      and receptor like kinase, known to affect plant development, appeared to be
      common protein family encoded by several loci responsible for grain size and
      shape. CONCLUSION: Conclusively, we demonstrated the application and integration
      of multiple approaches including high throughput phenotyping using DI, genome
      wide association studies (GWAS) and in silico functional analysis of candidate
      loci to analyze target traits, and identify candidate genomic regions underlying
      these traits. These approaches provided great opportunity to understand the
      breeding value of SHWs for improving grain weight and enhanced our deep
      understanding on molecular genetics of grain weight in wheat.

PMID- 24884377
TI  - CONSTANS is a photoperiod regulated activator of flowering in sorghum.
AB  - BACKGROUND: Sorghum genotypes used for grain production in temperate regions are
      photoperiod insensitive and flower early avoiding adverse environments during the
      reproductive phase. In contrast, energy sorghum hybrids are highly photoperiod
      sensitive with extended vegetative phases in long days, resulting in enhanced
      biomass accumulation. SbPRR37 and SbGHD7 contribute to photoperiod sensitivity in
      sorghum by repressing expression of SbEHD1 and FT-like genes, thereby delaying
      flowering in long days with minimal influence in short days (PNAS_108:16469
      16474, 2011; Plant Genome_in press, 2014). The GIGANTEA (GI)-CONSTANS (CO)
      FLOWERING LOCUS T (FT) pathway regulates flowering time in Arabidopsis and the
      grasses (J Exp Bot_62:2453-2463, 2011). In long day flowering plants, such as
      Arabidopsis and barley, CONSTANS activates FT expression and flowering in long
      days. In rice, a short day flowering plant, Hd1, the ortholog of CONSTANS,
      activates flowering in short days and represses flowering in long days. RESULTS:
      Quantitative trait loci (QTL) that modify flowering time in sorghum were
      identified by screening Recombinant Inbred Lines (RILs) derived from BTx642 and
      Tx7000 in long days, short days, and under field conditions. Analysis of the
      flowering time QTL on SBI-10 revealed that BTx642 encodes a recessive CONSTANS
      allele containing a His106Tyr substitution in B-box 2 known to inactivate
      CONSTANS in Arabidopsis thaliana. Genetic analysis characterized sorghum CONSTANS
      as a floral activator that promotes flowering by inducing the expression of EARLY
      HEADING DATE 1 (SbEHD1) and sorghum orthologs of the maize FT genes ZCN8 (SbCN8)
      and ZCN12 (SbCN12). The floral repressor PSEUDORESPONSE REGULATOR PROTEIN 37
      (PRR37) inhibits sorghum CONSTANS activity and flowering in long days.
      CONCLUSION: Sorghum CONSTANS is an activator of flowering that is repressed post
      transcriptionally in long days by the floral inhibitor PRR37, contributing to
      photoperiod sensitive flowering in Sorghum bicolor, a short day plant.

PMID- 24884378
TI  - Super-resolution microscopy using standard fluorescent proteins in intact cells
      under cryo-conditions.
AB  - We introduce a super-resolution technique for fluorescence cryo-microscopy based
      on photoswitching of standard genetically encoded fluorescent marker proteins in
      intact mammalian cells at low temperature (81 K). Given the limit imposed by the
      lack of cryo-immersion objectives, current applications of fluorescence cryo
      microscopy to biological specimens achieve resolutions between 400-500 nm only.
      We demonstrate that the single molecule characteristics of reversible
      photobleaching of mEGFP and mVenus at liquid nitrogen temperature are suitable
      for the basic concept of single molecule localization microscopy. This enabled us
      to perform super-resolution imaging of vitrified biological samples and to
      visualize structures in unperturbed fast frozen cells for the first time with a
      structural resolution of ~125 nm (average single molecule localization accuracy
      ~40 nm), corresponding to a 3-5 fold resolution improvement.

PMID- 24884381
TI  - Investigation of publication bias in meta-analyses of diagnostic test accuracy: a
      meta-epidemiological study.
AB  - BACKGROUND: The validity of a meta-analysis can be understood better in light of
      the possible impact of publication bias. The majority of the methods to
      investigate publication bias in terms of small study-effects are developed for
      meta-analyses of intervention studies, leaving authors of diagnostic test
      accuracy (DTA) systematic reviews with limited guidance. The aim of this study
      was to evaluate if and how publication bias was assessed in meta-analyses of DTA,
      and to compare the results of various statistical methods used to assess
      publication bias. METHODS: A systematic search was initiated to identify DTA
      reviews with a meta-analysis published between September 2011 and January 2012.
      We extracted all information about publication bias from the reviews and the two
      by-two tables. Existing statistical methods for the detection of publication bias
      were applied on data from the included studies. RESULTS: Out of 1,335 references,
      114 reviews could be included. Publication bias was explicitly mentioned in 75
      reviews (65.8%) and 47 of these had performed statistical methods to investigate
      publication bias in terms of small study-effects: 6 by drawing funnel plots, 16
      by statistical testing and 25 by applying both methods. The applied tests were
      Egger's test (n = 18), Deeks' test (n = 12), Begg's test (n = 5), both the Egger
      and Begg tests (n = 4), and other tests (n = 2). Our own comparison of the
      results of Begg's, Egger's and Deeks' test for 92 meta-analyses indicated that up
      to 34% of the results did not correspond with one another. CONCLUSIONS: The
      majority of DTA review authors mention or investigate publication bias. They
      mainly use suboptimal methods like the Begg and Egger tests that are not
      developed for DTA meta-analyses. Our comparison of the Begg, Egger and Deeks
      tests indicated that these tests do give different results and thus are not
      interchangeable. Deeks' test is recommended for DTA meta-analyses and should be
      preferred.

PMID- 24884383
TI  - Utility of a primary care based transient ischaemic attack electronic decision
      support tool: a prospective sequential comparison.
AB  - BACKGROUND: Stroke is a major cause of death and disability worldwide. Reducing
      the incidence of stroke has the potential to not only improve health outcomes,
      but also lead to significant cost savings for health services. Transient
      ischaemic attacks (TIA) can herald an imminent stroke and following a TIA early
      initiation of best medical therapy significantly reduces the risk of subsequent
      stroke. To achieve time targets rapid access stroke specialist services have been
      promoted; however, a number of resource related barriers can impede specialist
      access and cause unnecessary time delays. Cross sector collaboration led to the
      development of a primary care based TIA/Stroke electronic decision support (EDS)
      tool. This study aimed to assess the impact of this tool on improving access and
      reducing management delays. METHODS: This is a prospective before (2009) versus
      after (2011) study of the effect on process of care following the implementation
      of EDS assisted TIA management in primary care. All patients presenting with TIA
      to secondary services were included. Outcomes assessed were TIA Guideline
      adherence and patient safety. RESULTS: Over the study period 266 patients
      presented for TIA assessment (130 in 2009 and 136 in 2011). Following EDS
      implementation the median delay to specialist assessment fell from 10 days in
      2009 to three days in 2011 (HR 1.45; 95% CI 1.13-1.86; p=0.001), the number of
      patients achieving optimal medical therapy within 24 hours rose from 43% to 57%
      (RR 1.33; 95% CI 1.02-1.71; p=0.04), carotid and CT imaging were achieved
      significantly faster (HR 1.52 (1.02-2.26) p=0.003 and HR 1.34 (1.16-1.78 p=0.002)
      respectively), and there were no adverse events associated with EDS use.
      CONCLUSION: The availability of TIA/Stroke electronic decision support in the
      primary care setting was associated with reductions in management delays without
      compromising patient safety.

PMID- 24884386
TI  - Involvement of dopamine D2 receptor in the diurnal changes of tuberoinfundibular
      dopaminergic neuron activity and prolactin secretion in female rats.
AB  - BACKGROUND: An endogenous dopaminergic (DA) tone acting on D3 receptors has been
      shown to inhibit tuberoinfundibular (TI) DA neuron activity and stimulate
      prolactin (PRL) surge in the afternoon of estrogen-primed ovariectomized (OVX+E2)
      rats. Whether D2 receptor (D2R) is also involved in the regulation of TIDA and
      PRL rhythms was determined in this study. RESULTS: Intracerebroventricular (icv)
      injection of PHNO, a D2R agonist, in the morning inhibited TIDA and midbrain DA
      neurons' activities, and stimulated PRL secretion. The effects of PHNO were
      significantly reversed by co-administration of raclopride, a D2R antagonist. A
      single injection of raclopride at 1200 h significantly reversed the lowered TIDA
      neuron activity and the increased serum PRL level at 1500 h. Dopamine D2R mRNA
      expression in medial basal hypothalamus (MBH) exhibited a diurnal rhythm, i.e.,
      low in the morning and high in the afternoon, which was opposite to that of TIDA
      neuron activity. The D2R rhythm was abolished in OVX+E2 rats kept under constant
      lighting but not in OVX rats with regular lighting exposures. Pretreatment with
      an antisense oligodeoxynucleotides (AODN, 10 MUg/3 MUl/day, icv) against D2R mRNA
      for 2 days significantly reduced D2R mRNAs in central DA neurons, and reversed
      both lowered TIDA neuron activity and increased serum PRL level in the afternoon
      on day 3. A diurnal rhythm of D2R mRNA expression was also observed in midbrain
      DA neurons and the rhythm was significantly knocked down by the AODN
      pretreatment. CONCLUSIONS: We conclude that a diurnal change of D2R mRNA
      expression in MBH may underlie the diurnal rhythms of TIDA neuron activity and
      PRL secretion in OVX+E2 rats.

PMID- 24884382
TI  - A comparison of risk factors for mortality from heart failure in Asian and non
      Asian populations: an overview of individual participant data from 32 prospective
      cohorts from the Asia-Pacific Region.
AB  - BACKGROUND: Most of what is known regarding the epidemiology of mortality from
      heart failure (HF) comes from studies within Western populations with few data
      available from the Asia-Pacific region where the burden of heart failure is
      increasing. METHODS: Individual level data from 543694 (85% Asian; 36% female)
      participants from 32 cohorts in the Asia Pacific Cohort Studies Collaboration
      were included in the analysis. Adjusted hazard ratios (HR) and 95% confidence
      intervals (CI) for mortality from HF were estimated separately for Asians and non
      Asians for a quintet of cardiovascular risk factors: systolic blood pressure,
      diabetes, body mass index, cigarette smoking and total cholesterol. All analyses
      were stratified by sex and study. RESULTS: During 3,793,229 person years of
      follow-up there were 614 HF deaths (80% Asian). The positive associations between
      elevated blood pressure, obesity, and cigarette smoking were consistent for
      Asians and non-Asians. There was evidence to indicate that diabetes was a weaker
      risk factor for death from HF for Asians compared with non-Asians: HR 1.26 (95%
      CI: 0.74-2.13) versus 3.04 (95% CI 1.76-5.25) respectively; p for interaction =
      0.022. Additional adjustment for covariates did not materially change the overall
      associations. There was no good evidence to indicate that total cholesterol was a
      risk factor for HF mortality in either population. CONCLUSIONS: Most traditional
      cardiovascular risk factors including elevated blood pressure, obesity and
      cigarette smoking appear to operate similarly to increase the risk of death from
      HF in Asians and non-Asians populations alike.

PMID- 24884389
TI  - Strategy selection in cue-based decision making.
AB  - People can make use of a range of heuristic and rational, compensatory strategies
      to perform a multiple-cue judgment task. It has been proposed that people are
      sensitive to the amount of cognitive effort required to employ decision
      strategies. Experiment 1 employed a dual-task methodology to investigate whether
      participants' preference for heuristic versus compensatory decision strategies
      can be altered by increasing the cognitive demands of the task. As indicated by
      participants' decision times, a secondary task interfered more with the
      performance of a heuristic than compensatory decision strategy but did not affect
      the proportions of participants using either type of strategy. A stimulus set
      effect suggested that the conjunction of cue salience and cue validity might play
      a determining role in strategy selection. The results of Experiment 2 indicated
      that when a perceptually salient cue was also the most valid, the majority of
      participants preferred a single-cue heuristic strategy. Overall, the results
      contradict the view that heuristics are more likely to be adopted when a task is
      made more cognitively demanding. It is argued that people employ 2 learning
      processes during training, one an associative learning process in which cue
      outcome associations are developed by sampling multiple cues, and another that
      involves the sequential examination of single cues to serve as a basis for a
      single-cue heuristic.

PMID- 24884387
TI  - Effective pulmonary delivery of an aerosolized plasmid DNA vaccine via surface
      acoustic wave nebulization.
AB  - BACKGROUND: Pulmonary-delivered gene therapy promises to mitigate vaccine safety
      issues and reduce the need for needles and skilled personnel to use them. While
      plasmid DNA (pDNA) offers a rapid route to vaccine production without side
      effects or reliance on cold chain storage, its delivery to the lung has proved
      challenging. Conventional methods, including jet and ultrasonic nebulizers, fail
      to deliver large biomolecules like pDNA intact due to the shear and cavitational
      stresses present during nebulization. METHODS: In vitro structural analysis
      followed by in vivo protein expression studies served in assessing the integrity
      of the pDNA subjected to surface acoustic wave (SAW) nebulisation. In vivo
      immunization trials were then carried out in rats using SAW nebulized pDNA
      (influenza A, human hemagglutinin H1N1) condensate delivered via intratracheal
      instillation. Finally, in vivo pulmonary vaccinations using pDNA for influenza
      was nebulized and delivered via a respirator to sheep. RESULTS: The SAW nebulizer
      was effective at generating pDNA aerosols with sizes optimal for deep lung
      delivery. Successful gene expression was observed in mouse lung epithelial cells,
      when SAW-nebulized pDNA was delivered to male Swiss mice via intratracheal
      instillation. Effective systemic and mucosal antibody responses were found in
      rats via post-nebulized, condensed fluid instillation. Significantly, we
      demonstrated the suitability of the SAW nebulizer to administer unprotected pDNA
      encoding an influenza A virus surface glycoprotein to respirated sheep via
      aerosolized inhalation. CONCLUSION: Given the difficulty of inducing functional
      antibody responses for DNA vaccination in large animals, we report here the first
      instance of successful aerosolized inhalation delivery of a pDNA vaccine in a
      large animal model relevant to human lung development, structure, physiology, and
      disease, using a novel, low-power (<1 W) surface acoustic wave (SAW) hand-held
      nebulizer to produce droplets of pDNA with a size range suitable for delivery to
      the lower respiratory airways.

PMID- 24884391
TI  - DMRforPairs: identifying differentially methylated regions between unique samples
      using array based methylation profiles.
AB  - BACKGROUND: Array based methylation profiling is a cost-effective solution to
      study the association between genome methylation and human disease & development.
      Available tools to analyze the Illumina Infinium HumanMethylation450 BeadChip
      focus on comparing methylation levels per locus. Other tools combine multiple
      probes into a range, identifying differential methylated regions (DMRs). These
      tools all require groups of samples to compare. However, comparison of unique,
      individual samples is essential in situations where larger sample sizes are not
      possible. RESULTS: DMRforPairs was designed to compare regional methylation
      status between unique samples. It identifies probe dense genomic regions and
      quantifies/tests their (difference in) methylation level between the samples. As
      a proof of concept, DMRforPairs is applied to public data from four human cell
      lines: two lymphoblastoid cell lines from healthy individuals and the cancer cell
      lines A431 and MCF7 (including 2 technical replicates each). DMRforPairs
      identified an increasing number of DMRs related to the sample phenotype when
      biological similarity of the samples decreased. DMRs identified by DMRforPairs
      were related to the biological origin of the cell lines. CONCLUSION: To our
      knowledge, DMRforPairs is the first tool to identify and visualize relevant and
      significant differentially methylated regions between unique samples.

PMID- 24884392
TI  - Developing the principles of chair based exercise for older people: a modified
      Delphi study.
AB  - BACKGROUND: Chair based exercise (CBE) is suggested to engage older people with
      compromised health and mobility in an accessible form of exercise. A systematic
      review looking at the benefits of CBE for older people identified a lack of
      clarity regarding a definition, delivery, purpose and benefits. This study aimed
      to utilise expert consensus to define CBE for older people and develop a core set
      of principles to guide practice and future research. METHODS: The framework for
      consensus was constructed through a team workshop identifying 42 statements
      within 7 domains. A four round electronic Delphi study with multi-disciplinary
      health care experts was undertaken. Statements were rated using a 5 point Likert
      scale of agreement and free text responses. A threshold of 70% agreement was used
      to determine consensus. Free text responses were analysed thematically. Between
      rounds a number of strategies (e.g., amended wording of statements, generation
      and removal of statements) were used to move towards consensus. RESULTS: 16
      experts agreed on 46 statements over four rounds of consultation (Round 1: 22
      accepted, 3 removed, 5 new and 17 modified; Round 2: 16 accepted, 0 removed, 4
      new and 6 modified; Round 3: 4 accepted, 2 removed, 0 new and 4 modified; Round
      4: 4 accepted, 0 removed, 0 new, 0 modified).Statements were accepted in all
      seven domains: the definition of CBE (5), intended users (3), potential benefits
      (8), structure (12), format (8), risk management (7) and evaluation (3).The
      agreed definition of CBE had five components: 1. CBE is primarily a seated
      exercise programme; 2. The purpose of using a chair is to promote stability in
      both sitting and standing; 3. CBE should be considered as part of a continuum of
      exercise for frail older people where progression is encouraged; 4. CBE should be
      used flexibly to respond to the changing needs of frail older people; and 5.
      Where possible CBE should be used as a starting point to progress to standing
      programmes. CONCLUSIONS: Consensus has been reached on a definition and a set of
      principles governing CBE for older people; this provides clarity for
      implementation and future research about CBE.

PMID- 24884393
TI  - Urine real-time polymerase chain reaction detection for children virus pneumonia
      with acute human cytomegalovirus infection.
AB  - BACKGROUND: Human cytomegalovirus (HCMV) is an important pathogen of viral
      pneumonia in children. The diagnosis of acute HCMV infection is complicated and
      difficult. METHODS: Clinical and laboratory data of 6063 hospitalized children
      with respiratory infection and 509 with respiratory virus infection alone were
      retrospectively analyzed. Urine and respiratory specimens of 186 hospitalized
      children with pneumonia were also prospectively collected. Real-time polymerase
      chain reaction (PCR) and a chemiluminescent assay were used to detect HCMV DNA
      copy number, the pp65 gene, and HCMV IgM. RESULTS: The patients with respiratory
      virus infection alone and those with pulmonary HCMV infection (n = 422) were
      mostly children aged <6 months old (82.91%, 422/509). The accuracy of urine HCMV
      DNA (82.32%) was higher than that of HCMV IgM (67.78%), indicating that PCR of
      urine samples is suitable for determining pediatric acute pulmonary HCMV
      infection. There was no significant difference in detecting HCMV DNA or the pp65
      gene between urinary and respiratory specimens (P > 0.05) in 186 pediatric
      pneumonia cases. The accuracy of the pp65 gene measured in urine for determining
      acute pulmonary HCMV infection was the highest (93.01%). CONCLUSIONS: Our study
      shows a novel method for investigating acute pulmonary HCMV infection in children
      by using real-time PCR and non-invasive samples. This study also highlights the
      superiority and potential use of the pp65 gene as an important target for the
      diagnosis of acute pulmonary HCMV infection.

PMID- 24884396
TI  - Incidence and etiology of hemolytic-uremic syndrome in children in Norway, 1999
      2008--a retrospective study of hospital records to assess the sensitivity of
      surveillance.
AB  - BACKGROUND: Public awareness of hemolytic-uremic syndrome (HUS), especially
      related to Shiga toxin-producing Escherichia coli (STEC), has increased in Europe
      in recent years; accentuated in Norway by a national outbreak in 2006 and in a
      European context especially by the 2011 outbreak originating in Germany. As STEC
      surveillance is difficult due to diagnostic challenges in detecting non-O157
      infections, surveillance of HUS can be used to indicate the burden of STEC
      infection. Until 2006, notification of HUS to the Norwegian Communicable Disease
      Surveillance System (MSIS) was based on microbiologically confirmed infection
      with enterohemorrhagic Escherichia coli (EHEC), humanpathogenic STEC. In 2006,
      diarrhea-associated HUS (D(+)HUS) was made notifiable based on clinical criteria
      alone. The incidence and etiology of HUS in children in Norway has not previously
      been described. METHODS: In order to assess the sensitivity of STEC and D+HUS
      surveillance and describe the incidence and etiology of HUS in children in
      Norway, we conducted a nationwide retrospective study collecting data from
      medical records from pediatric departments for the period 1999-2008 and compared
      them with data from MSIS. Descriptive statistics are presented as proportions,
      median, average and mean values with ranges and as incidence rates, calculated
      using population numbers provided by official registries. RESULTS: Forty-seven
      HUS cases were identified, corresponding to an average annual incidence rate of
      0.5 cases per 100,000 children. Diarrhea-associated HUS was identified in 38
      (81%) cases, of which the median age was 29 months, 79% were <5 years of age and
      68% were girls. From 1999 to 2006, thirteen more diarrhea-associated HUS cases
      were identified than had been notified to MSIS. From the change in notification
      criteria to 2008, those identified corresponded to those notified. STEC infection
      was verified in 23 (49%) of the HUS cases, in which O157 was the most frequently
      isolated sporadic serogroup. CONCLUSIONS: Our results show that the incidence of
      HUS in children in Norway is low and suggest that D+HUS cases may be
      underreported when notification requires microbiological confirmation. This may
      also indicate underreporting of STEC infections.

PMID- 24884397
TI  - Association between adherence to an antimicrobial stewardship program and
      mortality among hospitalised cancer patients with febrile neutropaenia: a
      prospective cohort study.
AB  - BACKGROUND: Initial management of chemotherapy-induced febrile neutropaenia (FN)
      comprises empirical therapy with a broad-spectrum antimicrobial. Currently, there
      is sufficient evidence to indicate which antibiotic regimen should be
      administered initially. However, no randomized trial has evaluated whether
      adherence to an antimicrobial stewardship program (ASP) results in lower rates of
      mortality in this setting. The present study sought to assess the association
      between adherence to an ASP and mortality among hospitalised cancer patients with
      FN. METHODS: We conducted a prospective cohort study in a single tertiary
      hospital from October 2009 to August 2011. All adult patients who were admitted
      to the haematology ward with cancer and FN were followed up for 28 days. ASP
      adherence to the initial antimicrobial prescription was determined. The mortality
      rates of patients who were treated with antibiotics according to the ASP protocol
      were compared with those of patients treated with other antibiotic regimens. The
      multivariate Cox proportional hazards model and propensity score were used to
      estimate 28-day mortality risk. RESULTS: A total of 307 FN episodes in 169
      subjects were evaluated. The rate of adherence to the ASP was 53%. In a Cox
      regression analysis, adjusted for propensity scores and other potential
      confounding factors, ASP adherence was independently associated with lower
      mortality (hazard ratio, 0.36; 95% confidence interval, 0.14-0.92). CONCLUSIONS:
      Antimicrobial selection is important for the initial management of patients with
      FN, and adherence to the ASP, which calls for the rational use of antibiotics,
      was associated with lower mortality rates in this setting.

PMID- 24884398
TI  - Stroke survivors over-estimate their medication self-administration (MSA)
      ability, predicting memory loss.
AB  - BACKGROUND AND OBJECTIVE: Medication self-administration (MSA) may be cognitively
      challenging after stroke, but guidelines are currently lacking for identifying
      high-functioning stroke survivors who may have difficulty with this task.
      Complicating this matter, stroke survivors may not be aware of their cognitive
      problems (cognitive anosognosia) and may over-estimate their MSA competence. The
      authors wished to evaluate medication self-administration and MSA self-awareness
      in 24 consecutive acute stroke survivors undergoing inpatient rehabilitation, to
      determine if they would over-estimate their medication self-administration and if
      this predicted memory disorder. METHODS: Stroke survivors were tested on the
      Hopkins Medication Schedule and also their memory, naming mood and dexterity were
      evaluated, comparing their performance to 17 matched controls. RESULTS: The
      anosognosia ratio indicated MSA over-estimation in stroke survivors compared with
      controls--no other over-estimation errors were noted relative to controls. A
      strong correlation was observed between over-estimation of MSA ability and verbal
      memory deficit, suggesting that formally assessing MSA and MSA self-awareness may
      help detect cognitive deficits. CONCLUSIONS: Assessing medication self
      administration and MSA self-awareness may be useful in rehabilitation and
      successful community-return after stroke.

PMID- 24884399
TI  - The SAD PERSONS scale for suicide risk assessment: a systematic review.
AB  - The SAD PERSONS scale (SPS) is widely used for suicide risk assessment in
      clinical and educational settings. The study objective was to systematically
      review the SPS performance in clinical situations. A systematic search of
      electronic databases was conducted. Relevant descriptive, quality, and outcome
      data were reviewed. In the search, 149 studies were identified and 9 met
      inclusion criteria. Included studies were highly variable across outcome
      measures, populations, and assessment methods. Only 3 studies examined SPS
      performance in predicting suicide outcomes; none showed the scale accurately
      predicted suicidal behavior. Available literature is of limited quality and
      quantity. Insufficient evidence exists to support SPS use in assessment or
      prediction of suicidal behavior. Well-designed studies that address the observed
      limitations are required.

PMID- 24884400
TI  - Safety and efficacy of protease inhibitor based combination therapy in a single
      center "real-life" cohort of 110 patients with chronic hepatitis C genotype 1
      infection.
AB  - BACKGROUND: The combination of boceprevir or telaprevir with peginterferon-alfa
      and ribavirin for the treatment of patients infected with HCV genotype 1 has led
      to significantly increased rates of sustained virological response (SVR) in phase
      III trials. There is only limited data regarding the safety and efficacy in a
      "real-life" cohort. METHODS: We analyzed a cohort of 110 unselected HCV patients
      who started triple therapy from September 2011 to February 2013 by chart review
      with focus on the individual course of treatment, complications and outcome. We
      excluded 8 patients from analysis because of HIV-coinfection (N = 6) or status
      post liver transplant (N = 2). Importantly, 41 patients displayed F3 or F4
      fibrosis, 10 patients had a history of treatment with protease/polymerase
      inhibitors and 15 patients were prior partial- or null-responder. RESULTS: SVR12
      was achieved in 62 of the 102 patients (60.8%). A high rate of serious adverse
      events (N = 30) was observed in 22 patients including 2 fatalities in cirrhotic
      diabetes patients. Age >50 years, liver cirrhosis, bilirubin >1.1 mg/dl (P <
      0.01, each), platelets <100,000/MUl (P = 0.01), ASAT >100 U/l (P = 0.03) and
      albumin <=35 g/l (P = 0.04) at baseline were associated with occurence of a SAE.
      CONCLUSIONS: The frequency of SVR in a "real-life" treatment setting is slightly
      lower as compared to the results of the phase III trials for telaprevir or
      boceprevir. Importantly, we observed a high frequency of SAE in triple therapy,
      especially in patients with liver cirrhosis.

PMID- 24884402
TI  - Effect of anastrozole on hormone levels in postmenopausal women with early breast
      cancer.
AB  - OBJECTIVES: The aim of this study was to investigate the influence of anastrozole
      on serum hormone levels in postmenopausal women with hormone receptor-positive
      breast cancer. METHODS: We prospectively determined serum levels of estradiol,
      testosterone, dehydroepiandrosterone sulfate (DHEAS), sex hormone binding
      globulin (SHBG), follicle stimulating hormone (FSH) and luteinizing hormone (LH)
      at screening, as well as after 12 and 24 months of treatment and studied the
      associations with markers of bone turnover and bone mineral density (BMD).
      RESULTS: Altogether, a full set of hormone levels was available for 70 patients.
      Anastrozole treatment led to decreases of 92.1% for estradiol and 11.1% for LH
      over the observation period (p < 0.001). Conversely, FSH, DHEAS and testosterone
      concentrations increased by 5.9%, 33.3% and 50%, respectively (p < 0.001). SHBG
      levels remained stable during the 24 months of treatment (p = 0.355). There were
      modest associations between FSH, SHBG, CrossLaps and N-terminal propeptide of
      human procollagen type I (p < 0.05). Moreover, SHBG correlated positively with
      the BMD of femoral neck, total hip, total hip T-score, lumbar spine and the
      lumbar spine T-score, whereas FSH and estradiol correlated with the lumbar spine
      T-score (p < 0.05). CONCLUSIONS: During the 24 months of follow-up, treatment
      with anastrozole decreased the serum levels of estradiol and LH. Furthermore, we
      found notable increases of serum levels of FSH, DHEAS and testosterone in the
      first 12 months of treatment, stabilizing thereafter. Additionally, we were able
      to correlate hormone levels with markers of bone turnover and BMD for the first
      time in this regard.

PMID- 24884403
TI  - Effectiveness of motorcycle antilock braking systems (ABS) in reducing crashes,
      the first cross-national study.
AB  - OBJECTIVES: This study set out to evaluate the effectiveness of motorcycle
      antilock braking systems (ABS) in reducing real-life crashes. Since the European
      Parliament has voted on legislation making ABS mandatory on all new motorcycles
      over 125 cc from 2016, the fitment rate in Europe is likely to increase in the
      coming years. Though previous research has focused on mostly large displacement
      motorcycles, this study used police reports from Spain (2006-2009), Italy (2009),
      and Sweden (2003-2012) in order to analyze a wide range of motorcycles, including
      scooters, and compare countries with different motorcycling habits. METHODS: The
      statistical analysis used odds ratio calculations with an induced exposure
      approach. Previous research found that head-on crashes were the least ABS
      affected crash type and was therefore used as the nonsensitive crash type for ABS
      in these calculations. The same motorcycle models, with and without ABS, were
      compared and the calculations were carried out for each country separately.
      Crashes involving only scooters were further analyzed. RESULTS: The effectiveness
      of motorcycle ABS in reducing injury crashes ranged from 24% (95% confidence
      interval [CI], 12-36) in Italy to 29% (95% CI, 20-38) in Spain, and 34% (95% CI,
      16-52) in Sweden. The reductions in severe and fatal crashes were even greater,
      at 34% (95% CI, 24-44) in Spain and 42% (95% CI, 23-61) in Sweden. The overall
      reductions of crashes involving ABS-equipped scooters (at least 250 cc) were 27%
      (95% CI, 12-42) in Italy and 22% (95% CI, 2-42) in Spain. ABS on scooters with at
      least a 250 cc engine reduced severe and fatal crashes by 31% (95% CI, 12-50),
      based on Spanish data alone. CONCLUSIONS: At this stage, there is more than
      sufficient scientific-based evidence to support the implementation of ABS on all
      motorcycles, even light ones. Further research should aim at understanding the
      injury mitigating effects of motorcycle ABS, possibly in combination with
      combined braking systems.

PMID- 24884404
TI  - Molecular basis of DEL phenotype in the Chinese population.
AB  - BACKGROUND: Rh blood group system is the most complex and immunogenetic blood
      group system. Prevalent RHD alleles vary in different populations. We conducted
      the present study to examine the genotype of DEL individuals and to elucidate
      whether novel alleles exist in the Chinese population. METHODS: DEL phenotype was
      identified by a serologic adsorption-elution method. The nucleotide sequences of
      ten RHD exons and exon-intron boundary regions were evaluated by RHD gene
      specific PCR-SSP and sequencing. RESULTS: Of 42306 samples from individual donors
      and patients, 165 samples were typed as D-negative. Among these D-negative
      samples, 41 DEL individuals were observed. Thirty-seven DELs were confirmed to
      have the RHD1227A allele. Two DELs seemed to have RHD-CE-D hybrid alleles,
      including one RHD-CE (4-7)-D and one RHD-CE (2-5)-D. Two novel RHD alleles were
      found among the rest of the DEL samples, including one RHD93T > A and one RHD838G
      > A. CONCLUSION: In this study, about 24.85% (41/165) of the apparent D-negative
      Chinese individuals were DEL. RHD1227G > A is the most frequent allele in Chinese
      DEL phenotypes, accounting for 90.24% (37/41). The RHD-CE-D hybrid allele might
      be the second most frequent DEL allele in the Chinese population. Our study would
      contribute to the understanding of the molecular mechanism underlying D antigen
      expression of DEL individuals and provide useful information for designing
      suitable genotyping strategies in RhD-negative individuals in Asia.

PMID- 24884406
TI  - Binding free-energy calculation is a powerful tool for drug optimization:
      calculation and measurement of binding free energy for 7-azaindole derivatives to
      glycogen synthase kinase-3beta.
AB  - Present computational lead (drug)-optimization is lacking in thermodynamic
      tactics. To examine whether calculation of binding free-energy change (DeltaG) is
      effective for the lead-optimization process, binding DeltaGs of 7-azaindole
      derivatives to the ATP binding site of glycogen synthase kinase-3beta (GSK-3beta)
      were calculated. The result was a significant correlation coefficient of r =
      0.895 between calculated and observed DeltaGs. This indicates that calculated
      DeltaG reflects the inhibitory activities of 7-azaindole derivatives. In addition
      to quantitative estimation of activity, DeltaG calculation characterizes the
      thermodynamic behavior of 7-azaindole derivatives, providing also useful
      information for inhibitor optimization on affinity to water molecules. 

PMID- 24884407
TI  - Polychondritis presenting with oculomotor and abducens nerve palsies as the
      initial manifestation.
AB  - We treated a patient with relapsing polychondritis (RP) who presented with
      intermittent oculomotor and abducens nerve palsies as the first manifestation.
      Ear swelling and laryngeal edema emerged 7 months later, which led us to diagnose
      him with RP. Moderate doses of glucocorticoid resolved all symptoms. Our
      experience with RP accompanied by oculomotor nerve palsy suggests that RP should
      be considered in patients with cranial nerve palsies so that they may be promptly
      diagnosed and treated. 

PMID- 24884405
TI  - KNOW-KT (KoreaN cohort study for outcome in patients with kidney transplantation:
      a 9-year longitudinal cohort study): study rationale and methodology.
AB  - BACKGROUND: Asian patients undergoing kidney transplantation (KT) generally have
      better renal allograft survival and a lower burden of cardiovascular disease than
      those of other racial groups. The KNOW-KT aims to explore allograft survival
      rate, cardiovascular events, and metabolic profiles and to elucidate the risk
      factors in Korean KT patients. METHODS: KNOW-KT is a multicenter, observational
      cohort study encompassing 8 transplant centers in the Republic of Korea. KNOW-KT
      will enroll 1,000 KT recipients between 2012 and 2015 and follow them up to 9
      years. At the time of KT and at pre-specified intervals, clinical information,
      laboratory test results, and functional and imaging studies on cardiovascular
      disease and metabolic complications will be recorded. Comorbid status will be
      assessed by the age-adjusted Charlson co-morbidity index. Medication adherence
      and information on quality of life (QoL) will be monitored periodically. The QoL
      will be assessed by the Kidney Disease Quality of Life Short Form. Donors will
      include both living donors and deceased donors whose status will be assessed by
      the Kidney Donor Risk Index. Primary endpoints include graft loss and patient
      mortality. Secondary endpoints include renal functional deterioration (a decrease
      in eGFR to <30 mL/min/1.73 m2), acute rejection, cardiovascular event,
      albuminuria, new-onset diabetes after transplant, and QoL. Data on other adverse
      outcomes including episodes of infection, malignancy, recurrence of original
      renal disease, fracture, and hospitalization will also be collected. A bio-bank
      has been established for the acquisition of DNA, RNA, and protein from serum and
      urine samples of recipients at regular intervals. Bio-samples from donors will
      also be collected at the time of KT. KNOW-KT was registered in an international
      clinical trial registry (NCT02042963 at http://www.clinicaltrials.gov) on January
      20th, 2014. CONCLUSION: The KNOW-KT, the first large-scale cohort study in Asian
      KT patients, is expected to represent the Asian KT population and provide
      information on their natural course, complications, and risk factors for
      complications.

PMID- 24884408
TI  - A highly conserved WDYPKCDRA epitope in the RNA directed RNA polymerase of human
      coronaviruses can be used as epitope-based universal vaccine design.
AB  - BACKGROUND: Coronaviruses are the diverse group of RNA virus. From 1960, six
      strains of human coronaviruses have emerged that includes SARS-CoV and the recent
      infection by deadly MERS-CoV which is now going to cause another outbreak.
      Prevention of these viruses is urgent and a universal vaccine for all strain
      could be a promising solution in this circumstance. In this study we aimed to
      design an epitope based vaccine against all strain of human coronavirus. RESULTS:
      Multiple sequence alignment (MSA) approach was employed among spike (S), membrane
      (M), enveloped (E) and nucleocapsid (N) protein and replicase polyprotein 1ab to
      identify which one is highly conserve in all coronaviruses strains. Next, we use
      various in silico tools to predict consensus immunogenic and conserved peptide.
      We found that conserved region is present only in the RNA directed RNA polymerase
      protein. In this protein we identified one epitope WDYPKCDRA is highly
      immunogenic and 100% conserved among all available human coronavirus strains.
      CONCLUSIONS: Here we suggest in vivo study of our identified novel peptide
      antigen in RNA directed RNA polymerase protein for universal vaccine--which may
      be the way to prevent all human coronavirus disease.

PMID- 24884409
TI  - Dementia with Lewy bodies versus nonconvulsive status epilepticus in the
      diagnosis of a patient with cognitive dysfunction, complex visual hallucinations
      and periodic abnormal waves in EEG: a case report.
AB  - BACKGROUND: The diagnosis of dementia with Lewy bodies (DLB) is often challenging
      in elderly individuals, not only for its various clinical features, sometimes,
      but also for its rare changes of periodic synchronous discharges (PSD) in
      electroencephalogram ( EEG). So, we reported one case of DLB and gave a detailed
      analysis. CASE PRESENTATION: A Chinese patient (Female, 56 years old) presented
      with progressive cognitive decline and complex visual hallucinations. Several
      days after admission, she gradually showed focal myoclonic jerks. Mini-Mental
      State Examination (MMSE) score was 19/30, EEG revealed PSD, Cerebrospinal fluid
      and 14-3-3 brain protein was negative, Magnetic resonance imaging (MRI) showed
      diffuse atrophy. To differentiate the PSD derived from DLB or from late-onset
      Absence Status Epilepticus, we have given the treatment with intravenous
      valproate (1200 mg/24 h) and diazepam 20 mg under the EEG monitor, a clinical
      improvement was absent and PSD in EEG did not disappear. Two weeks later, the
      patient showed akinetic-rigid syndrome and PSD in EEG persisted for a long time.
      According to her history and therapy, a clinical diagnosis of DLB has been made,
      but no autopsy for confirmation, and in the following visit, she has a poor
      prognosis. CONCLUSION: PSD in EEG may occasionally be recorded in
      neurodegenerative disorders such as AD, DLB other than CJD or NCSE. Hence it
      should not dissuade clinicians from the diagnosis of DLB where the clinical and
      neuropsychological findings were consistent with suggested diagnostic criteria
      for DLB.

PMID- 24884410
TI  - The effect of social support around pregnancy on postpartum depression among
      Canadian teen mothers and adult mothers in the maternity experiences survey.
AB  - BACKGROUND: Postpartum depression (PPD) is a mood disorder that affects 10-20
      percent of women, and can begin any time during first year after delivery lasting
      for months. Social support may decrease risk of depression during pregnancy for
      women. However, literature shows that the amount of social support received
      during and after pregnancy is different for teen mothers and adult mothers. This
      study examined the effects of social support received during and after pregnancy
      on PPD among Canadian women and identified if the relationship was different for
      teen mothers compared to adult mothers. METHODS: The study was based on secondary
      analysis of the Maternity Experiences Survey. A total of 6,421 women with
      singleton live births, aged 15 years and older were analyzed. Teen mothers were
      identified as 15-19 years old and adult mothers were identified as 20 years and
      older. The main outcome of the study was PPD, which was evaluated using the
      Edinburg Postnatal Depression Scale. The main independent variable was social
      support received during pregnancy and after birth. Logistic regression was
      computed to assess the relationship between social support and PPD after
      adjusting for confounding variables and age as an interaction term. Adjusted Odds
      Ratios and 95% Confidence Intervals were reported. RESULTS: PPD was experienced
      by 14.0% among teen mothers and 7.2% among adult mothers (p < .001). Overall,
      teen mothers reported receiving more support during pregnancy and after birth
      than adult mothers (p < .010). The relationship between social support and PPD
      did not significantly differ for teen compared to adult mothers. Both teen and
      adult mothers were approximately five times more likely to experience PPD if they
      received no support or minimal support after the birth of the baby (95% CI, 3.51
      7.36). CONCLUSION: Receiving social support especially after birth is important
      for mothers of all ages to reduce the risk of PPD.

PMID- 24884411
TI  - A multilocus timescale for oomycete evolution estimated under three distinct
      molecular clock models.
AB  - BACKGROUND: Molecular clock methodologies allow for the estimation of divergence
      times across a variety of organisms; this can be particularly useful for groups
      lacking robust fossil histories, such as microbial eukaryotes with few
      distinguishing morphological traits. Here we have used a Bayesian molecular clock
      method under three distinct clock models to estimate divergence times within
      oomycetes, a group of fungal-like eukaryotes that are ubiquitous in the
      environment and include a number of devastating pathogenic species. The earliest
      fossil evidence for oomycetes comes from the Lower Devonian (~400 Ma), however
      the taxonomic affinities of these fossils are unclear. RESULTS: Complete genome
      sequences were used to identify orthologous proteins among oomycetes, diatoms,
      and a brown alga, with a focus on conserved regulators of gene expression such as
      DNA and histone modifiers and transcription factors. Our molecular clock
      estimates place the origin of oomycetes by at least the mid-Paleozoic (~430-400
      Ma), with the divergence between two major lineages, the peronosporaleans and
      saprolegnialeans, in the early Mesozoic (~225-190 Ma). Divergence times estimated
      under the three clock models were similar, although only the strict and random
      local clock models produced reliable estimates for most parameters. CONCLUSIONS:
      Our molecular timescale suggests that modern pathogenic oomycetes diverged well
      after the origin of their respective hosts, indicating that environmental
      conditions or perhaps horizontal gene transfer events, rather than host
      availability, may have driven lineage diversification. Our findings also suggest
      that the last common ancestor of oomycetes possessed a full complement of
      eukaryotic regulatory proteins, including those involved in histone modification,
      RNA interference, and tRNA and rRNA methylation; interestingly no match to
      canonical DNA methyltransferases could be identified in the oomycete genomes
      studied here.

PMID- 24884412
TI  - Selection on synonymous codons in mammalian rhodopsins: a possible role in
      optimizing translational processes.
AB  - BACKGROUND: Synonymous codon usage can affect many cellular processes,
      particularly those associated with translation such as polypeptide elongation and
      folding, mRNA degradation/stability, and splicing. Highly expressed genes are
      thought to experience stronger selection pressures on synonymous codons. This
      should result in codon usage bias even in species with relatively low effective
      population sizes, like mammals, where synonymous site selection is thought to be
      weak. Here we use phylogenetic codon-based likelihood models to explore patterns
      of codon usage bias in a dataset of 18 mammalian rhodopsin sequences, the protein
      mediating the first step in vision in the eye, and one of the most highly
      expressed genes in vertebrates. We use these patterns to infer selection
      pressures on key translational mechanisms including polypeptide elongation,
      protein folding, mRNA stability, and splicing. RESULTS: Overall, patterns of
      selection in mammalian rhodopsin appear to be correlated with post
      transcriptional and translational processes. We found significant evidence for
      selection at synonymous sites using phylogenetic mutation-selection likelihood
      models, with C-ending codons found to have the highest relative fitness, and to
      be significantly more abundant at conserved sites. In general, these codons
      corresponded with the most abundant tRNAs in mammals. We found significant
      differences in codon usage bias between rhodopsin loops versus helices, though
      there was no significant difference in mean synonymous substitution rate between
      these motifs. We also found a significantly higher proportion of GC-ending codons
      at paired sites in rhodopsin mRNA secondary structure, and significantly lower
      synonymous mutation rates in putative exonic splicing enhancer (ESE) regions than
      in non-ESE regions. CONCLUSIONS: By focusing on a single highly expressed gene we
      both distinguish synonymous codon selection from mutational effects and
      analytically explore underlying functional mechanisms. Our results suggest that
      codon bias in mammalian rhodopsin arises from selection to optimally balance high
      overall translational speed, accuracy, and proper protein folding, especially in
      structurally complicated regions. Selection at synonymous sites may also be
      contributing to mRNA stability and splicing efficiency at exonic-splicing
      enhancer (ESE) regions. Our results highlight the importance of investigating
      highly expressed genes in a broader phylogenetic context in order to better
      understand the evolution of synonymous substitutions.

PMID- 24884413
TI  - The influences of PRG-1 on the expression of small RNAs and mRNAs.
AB  - BACKGROUND: In metazoans, Piwi-related Argonaute proteins play important roles in
      maintaining germline integrity and fertility and have been linked to a class of
      germline-enriched small RNAs termed piRNAs. Caenorhabditis elegans encodes two
      Piwi family proteins called PRG-1 and PRG-2, and PRG-1 interacts with the C.
      elegans piRNAs (21U-RNAs). Previous studies found that mutation of prg-1 causes a
      marked reduction in the expression of 21U-RNAs, temperature-sensitive defects in
      fertility and other phenotypic defects. RESULTS: In this study, we wanted to
      systematically demonstrate the function of PRG-1 in the regulation of small RNAs
      and their targets. By analyzing small RNAs and mRNAs with and without a mutation
      in prg-1 during C. elegans development, we demonstrated that (1) mutation of prg
      1 leads to a decrease in the expression of 21U-RNAs, and causes 35 ~ 40% of
      miRNAs to be down-regulated; (2) in C. elegans, approximately 3% (6% in L4) of
      protein-coding genes are differentially expressed after mutating prg-1, and 60 ~
      70% of these substantially altered protein-coding genes are up-regulated; (3) the
      target genes of the down-regulated miRNAs and the candidate target genes of the
      down-regulated 21U-RNAs are enriched in the up-regulated protein-coding genes;
      and (4) PRG-1 regulates protein-coding genes by down-regulating small RNAs
      (miRNAs and 21U-RNAs) that target genes that participate in the development of C.
      elegans. CONCLUSIONS: In prg-1-mutated C. elegans, the expression of miRNAs and
      21U-RNAs was reduced, and the protein-coding targets, which were associated with
      the development of C. elegans, were up-regulated. This may be the mechanism
      underlying PRG-1 function.

PMID- 24884415
TI  - Women's perception of pre-hospital labour duration and obstetrical outcomes; a
      prospective cohort study.
AB  - BACKGROUND: Progress during early labour may impact subsequent labour
      trajectories. Women admitted to hospital in latent phase (<3 cm cervical
      dilation) labour have been shown to be at higher risk of obstetrical
      interventions. METHODS: We conducted a secondary analysis of data from a
      randomized controlled trial of 1247 healthy nulliparous women in spontaneous
      labour at term with a singleton fetus in cephalic presentation at seven hospitals
      in Southwestern British Columbia. We computed relative risks and their 95%
      confidence intervals to examine our primary outcome of cesarean section and
      secondary outcomes including obstetrical interventions and maternal and newborn
      outcomes according to women's perception of length of pre-hospital labour. Women
      were asked on admission to hospital how long they had been experiencing
      contractions prior to coming to hospital. RESULTS: Women indicating that they had
      been in labour for 24 hours or longer at the time of hospital admission were at
      elevated risk for cesarean birth, relative risk (RR) 1.40, (95% Confidence
      Intervals 1.15-1.72), admission with a cervical dilation of 3 cm or less, RR 1.21
      (1.07-1.36), more obstetrical interventions including continuous electronic fetal
      monitoring RR 1.11 (1.03-1.20), augmentation of labour RR 1.33 (1.23-1.44), use
      of narcotic RR 1.21 (1.06-1.37) and epidural analgesia RR 1.18 (1.09-1.28).
      Adverse neonatal outcomes did not differ apart from a significant increase in
      meconium-stained amniotic fluid RR 1.60 (1.09-2.35). CONCLUSIONS: A single
      question asked of women on presentation to hospital was an important predictor of
      cesarean birth and may have utility in identifying women who would benefit from
      close observation and more active management of labour.

PMID- 24884414
TI  - EXPRSS: an Illumina based high-throughput expression-profiling method to reveal
      transcriptional dynamics.
AB  - BACKGROUND: Next Generation Sequencing technologies have facilitated differential
      gene expression analysis through RNA-seq and Tag-seq methods. RNA-seq has biases
      associated with transcript lengths, lacks uniform coverage of regions in mRNA and
      requires 10-20 times more reads than a typical Tag-seq. Most existing Tag-seq
      methods either have biases or not high throughput due to use of restriction
      enzymes or enzymatic manipulation of 5' ends of mRNA or use of RNA ligations.
      RESULTS: We have developed EXpression Profiling through Randomly Sheared cDNA tag
      Sequencing (EXPRSS) that employs acoustic waves to randomly shear cDNA and
      generate sequence tags at a relatively defined position (~150-200 bp) from the 3'
      end of each mRNA. Implementation of the method was verified through comparative
      analysis of expression data generated from EXPRSS, NlaIII-DGE and Affymetrix
      microarray and through qPCR quantification of selected genes. EXPRSS is a strand
      specific and restriction enzyme independent tag sequencing method that does not
      require cDNA length-based data transformations. EXPRSS is highly reproducible, is
      high-throughput and it also reveals alternative polyadenylation and
      polyadenylated antisense transcripts. It is cost-effective using barcoded
      multiplexing, avoids the biases of existing SAGE and derivative methods and can
      reveal polyadenylation position from paired-end sequencing. CONCLUSIONS: EXPRSS
      Tag-seq provides sensitive and reliable gene expression data and enables high
      throughput expression profiling with relatively simple downstream analysis.

PMID- 24884417
TI  - Decreased expression of long noncoding RNA GAS5 indicates a poor prognosis and
      promotes cell proliferation in gastric cancer.
AB  - BACKGROUND: Gastric cancer is the second leading cause of cancer death and
      remains a major clinical challenge due to poor prognosis and limited treatment
      options. Long noncoding RNAs (lncRNAs) have emerged recently as major players in
      tumor biology and may be used for cancer diagnosis, prognosis, and potential
      therapeutic targets. Although downregulation of lncRNA GAS5 (Growth Arrest
      Specific Transcript) in several cancers has been studied, its role in gastric
      cancer remains unknown. Our studies were designed to investigate the expression,
      biological role and clinical significance of GAS5 in gastric cancer. METHODS:
      Expression of GAS5 was analyzed in 89 gastric cancer tissues and five gastric
      cancer cell lines by quantitative reverse-transcription polymerase chain reaction
      (qRT-PCR). Over-expression and RNA interference (RNAi) approaches were used to
      investigate the biological functions of GAS5. The effect of GAS5 on proliferation
      was evaluated by MTT and colony formation assays, and cell apoptosis was
      evaluated by hochest stainning. Gastric cancer cells transfected with pCDNA3.1 
      GAS5 were injected into nude mice to study the effect of GAS5 on tumorigenesis in
      vivo. Protein levels of GAS5 targets were determined by western blot analysis.
      Differences between groups were tested for significance using Student's t-test
      (two-tailed). RESULTS: We found that GAS5 expression was markedly downregulated
      in gastric cancer tissues, and associated with larger tumor size and advanced
      pathologic stage. Patients with low GAS5 expression level had poorer disease-free
      survival (DFS; P = 0.001) and overall survival (OS; P < 0.001) than those with
      high GAS5 expression. Further multivariable Cox regression analysis suggested
      that decreased GAS5 was an independent prognostic indicator for this disease (P =
      0.006, HR = 0.412; 95%CI = 2.218-0.766). Moreover, ectopic expression of GAS5 was
      demonstrated to decrease gastric cancer cell proliferation and induce apoptosis
      in vitro and in vivo, while downregulation of endogenous GAS5 could promote cell
      proliferation. Finally, we found that GAS5 could influence gastric cancer cells
      proliferation, partly via regulating E2F1 and P21 expression. CONCLUSION: Our
      study presents that GAS5 is significantly downregulated in gastric cancer tissues
      and may represent a new marker of poor prognosis and a potential therapeutic
      target for gastric cancer intervention.

PMID- 24884418
TI  - The chick chorioallantoic membrane as an in vivo xenograft model for Burkitt
      lymphoma.
AB  - BACKGROUND: Burkitt lymphoma (BL) is an aggressive malignancy that arises from B
      cells and belongs to the group of Non-Hodgkin lymphomas (NHL). Due to the lack of
      appropriate in vivo models NHL research is mainly performed in vitro. Here, we
      studied the use of the chick chorioallantoic membrane (CAM) for the generation of
      human BL xenograft tumors, which we compared with known characteristics of the
      human disease. METHODS: In order to generate experimental BL tumors, we
      inoculated human BL2B95 and BL2-GFP cells on the CAM. BL2B95 xenograft-tumors
      were grown for seven days and subsequently analyzed with transmission electron
      and immunofluorescence microscopy, as well as histological staining approaches.
      BL2-GFP cells were studied at regular intervals up to seven days, and their
      metastatic behavior was visualized with intravital immunofluorescence techniques.
      RESULTS: Xenografted BL2B95 cells formed solid tumors in the CAM model with a
      Ki67-index greater than 90%, preservation of typical tumor markers (CD10, CD19,
      CD20), a 'starry sky' morphology, production of agyrophilic fibers in the stroma,
      formation of blood and lymphatic vessels and lymphogenic dissemination of BL2B95
      to distant sites. We identified macrophages, lymphocytes and heterophilic
      granulocytes (chick homolog of neutrophils) as the most abundant immune cells in
      the experimental tumors. BL2-GFP cells could be traced in real-time during their
      distribution in the CAM, and the first signs for their dissemination were visible
      after 2-3 days. CONCLUSIONS: We show that xenografted BL2B95 cells generate
      tumors in the CAM with a high degree of cellular, molecular and proliferative
      concord with the human disease, supporting the application of the CAM model for
      NHL research with a focus on tumor-stroma interactions. Additionally we report
      that BL2-GFP cells, grafted on the CAM of ex ovo cultured chick embryos, provide
      a powerful tool to study lymphogenic dissemination in real-time.

PMID- 24884419
TI  - Individual risk of cutaneous melanoma in New Zealand: developing a clinical
      prediction aid.
AB  - BACKGROUND: New Zealand and Australia have the highest melanoma incidence rates
      worldwide. In New Zealand, both the incidence and thickness have been increasing.
      Clinical decisions require accurate risk prediction but a simple list of genetic,
      phenotypic and behavioural risk factors is inadequate to estimate individual risk
      as the risk factors for melanoma have complex interactions. In order to offer
      tailored clinical management strategies, we developed a New Zealand prediction
      model to estimate individual 5-year absolute risk of melanoma. METHODS: A
      population-based case-control study (368 cases and 270 controls) of melanoma risk
      factors provided estimates of relative risks for fair-skinned New Zealanders aged
      20-79 years. Model selection techniques and multivariate logistic regression were
      used to determine the important predictors. The relative risks for predictors
      were combined with baseline melanoma incidence rates and non-melanoma mortality
      rates to calculate individual probabilities of developing melanoma within 5
      years. RESULTS: For women, the best model included skin colour, number of moles >
      =5 mm on the right arm, having a 1st degree relative with large moles, and a
      personal history of non-melanoma skin cancer (NMSC). The model correctly
      classified 68% of participants; the C-statistic was 0.74. For men, the best model
      included age, place of occupation up to age 18 years, number of moles > =5 mm on
      the right arm, birthplace, and a history of NMSC. The model correctly classified
      67% of cases; the C-statistic was 0.71. CONCLUSIONS: We have developed the first
      New Zealand risk prediction model that calculates individual absolute 5-year risk
      of melanoma. This model will aid physicians to identify individuals at high risk,
      allowing them to individually target surveillance and other management
      strategies, and thereby reduce the high melanoma burden in New Zealand.

PMID- 24884420
TI  - Cell proliferation and apoptosis in rat mammary glands following combinational
      exposure to bisphenol A and genistein.
AB  - BACKGROUND: Humans are exposed to an array of both harmful and beneficial
      hormonally active compounds in the environment and through diet. Two such
      chemicals are Bisphenol A (BPA), a plasticizer, and genistein, a component of
      soy. Prepubertal exposure to BPA increased mammary carcinogenesis, while
      genistein suppressed cancer in a chemically-induced model of rodent mammary
      cancer. The purpose of this research was to determine the effects of
      combinational exposure to genistein and BPA on cell proliferation, apoptosis, and
      associated proteins as markers of cancer in mammary glands of rats exposed
      prepubertally to these environmental chemicals. METHODS: Prepubertal rats
      (postpartum days (PND) 2-20) were exposed through lactation via nursing dams
      treated orally with sesame oil (SO), BPA, genistein, or a combination of BPA and
      genistein (BPA + Gen). Cell proliferation, apoptosis and protein expressions were
      investigated for mechanistic studies in mammary glands of rats exposed to these
      environmental chemicals. RESULTS: Prepubertal exposure to genistein increased
      cell proliferation in mammary glands of PND21 rats, while BPA increased cell
      proliferation in adult (PND50) rats. Prepubertal combinational exposure to BPA +
      Gen increased cell proliferation and reduced apoptosis in PND21 rats, but reduced
      cell proliferation and increased apoptosis in PND50 rats. The altered mechanisms
      behind these cellular responses appear to be centered on differential protein
      expression of caspases, PARP, Bad, p21, Akts, PTEN, ER-beta and SRCs 1-3, in the
      rat mammary gland. CONCLUSION: Prepubertal BPA exposure resulted in increased
      cell proliferation in mammary glands of PND50 rats, a process associated with
      increased risk of cancer development in a chemically-induced mammary cancer. On
      the other hand, genistein stimulated cell proliferation at PND21, a process that
      correlates with mammary gland maturation and chemoprevention. In contrast to
      single chemical exposure, combinational exposure to BPA + Gen performed most
      similarly to genistein exposure alone. BPA + Gen increased cell proliferation at
      PND21, suggesting mammary gland maturation, and decreased cell proliferation
      while increasing apoptosis in PND50 rats, suggesting mammary chemoprevention.
      Differential expression of proteins involved in regulating cell proliferation and
      apoptosis lend support to these chemicals, both alone and in combination,
      altering mammary gland cancer susceptibility.

PMID- 24884422
TI  - Hydrocortisone concentration influences time to clinically significant healing of
      acute inflammation of the ocular surface and adnexa - results from a double-blind
      randomized controlled trial.
AB  - BACKGROUND: The efficacy of topical ophthalmic corticosteroids depends upon small
      modifications in preparations, such as drug concentration.The aim of this study
      was to confirm that hydrocortisone acetate (HC-ac) ophthalmic ointments of 2.5%
      and 1% are more effective than a 0.5% eye ointment. METHODS: In this randomized,
      double-blind, placebo-controlled, parallel-group clinical study, the change of
      signs and symptoms of acute inflammation of the ocular surface and adnexa was
      evaluated in 411 subjects. RESULTS: Median time to clinically relevant response
      as estimated by 50% reduction in clinical signs and symptoms (CSS) total score
      over the entire trial was similar for subjects treated with HC-ac 2.5% (73.5 h)
      and for subjects treated with HC-ac 1.0% (67.7 h) and was considerably and
      significantly longer for subjects treated with HC-ac 0.5% (111.8 h) [p < 0.001
      for both dosages]. All trial medications were safe and well tolerated.
      CONCLUSION: Hydrocortisone acetate 2.5% and Hydrocortisone acetate 1% eye
      ointments are efficacious and safe treatments for acute inflammations of the
      ocular surface or adnexa, and showed significantly better efficacy than a control
      group treated with Hydrocortisone acetate 0.5% therapy. TRIAL REGISTRATION:
      Current Controlled Trials ISRCTN15464650.

PMID- 24884423
TI  - High-throughput capturing and characterization of mutations in essential genes of
      Caenorhabditis elegans.
AB  - BACKGROUND: Essential genes are critical for the development of all organisms and
      are associated with many human diseases. These genes have been a difficult
      category to study prior to the availability of balanced lethal strains. Despite
      the power of targeted mutagenesis, there are limitations in identifying mutations
      in essential genes. In this paper, we describe the identification of coding
      regions for essential genes mutated using forward genetic screens in
      Caenorhabditis elegans. The lethal mutations described here were isolated and
      maintained by a wild-type allele on a rescuing duplication. RESULTS: We applied
      whole genome sequencing to identify the causative molecular lesion resulting in
      lethality in existing C. elegans mutant strains. These strains are balanced and
      can be easily maintained for subsequent characterization. Our method can be
      effectively used to analyze mutations in a large number of essential genes. We
      describe here the identification of 64 essential genes in a region of chromosome
      I covered by the duplication sDp2. Of these, 42 are nonsense mutations, six are
      splice signal mutations, one deletion, and 15 are non-synonymous mutations. Many
      of the essential genes in this region function in cell cycle, transcriptional
      regulation, and RNA processing. CONCLUSIONS: The essential genes identified here
      are represented by mutant strains, many of which have more than one mutant
      allele. The genetic resource can be utilized to further our understanding of
      essential gene function and will be applicable to the study of C. elegans
      development, conserved cellular function, and ultimately lead to improved human
      health.

PMID- 24884424
TI  - DoMINO: Donor milk for improved neurodevelopmental outcomes.
AB  - BACKGROUND: Provision of mother's own milk is the optimal way to feed infants,
      including very low birth weight infants (VLBW, <1500 g). Importantly for VLBW
      infants, who are at elevated risk of neurologic sequelae, mother's own milk has
      been shown to enhance neurocognitive development. Unfortunately, the majority of
      mothers of VLBW infants are unable to provide an adequate supply of milk and thus
      supplementation with formula or donor milk is necessary. Given the association
      between mother's own milk and neurodevelopment, it is important to ascertain
      whether provision of human donor milk as a supplement may yield superior
      neurodevelopmental outcomes compared to formula.Our primary hypothesis is that
      VLBW infants fed pasteurized donor milk compared to preterm formula as a
      supplement to mother's own milk for 90 days or until hospital discharge,
      whichever comes first, will have an improved cognitive outcome as measured at 18
      months corrected age on the Bayley Scales of Infant Development, 3(rd) ed.
      Secondary hypotheses are that the use of pasteurized donor milk will: (1) reduce
      a composite of death and serious morbidity; (2) support growth; and (3) improve
      language and motor development. Exploratory research questions include: Will use
      of pasteurized donor milk: (1) influence feeding tolerance and nutrient intake
      (2) have an acceptable cost effectiveness from a comprehensive societal
      perspective? METHODS/DESIGN: DoMINO is a multi-centre, intent-to-treat, double
      blinded, randomized control trial. VLBW infants (n = 363) were randomized within
      four days of birth to either (1) pasteurized donor milk or (2) preterm formula
      whenever mother's own milk was unavailable. Study recruitment began in October
      2010 and was completed in December 2012. The 90 day feeding intervention is
      complete and long-term follow-up is underway. DISCUSSION: Preterm birth and its
      complications are a leading cause long-term morbidity among Canadian children.
      Strategies to mitigate this risk are urgently required. As mother's own milk has
      been shown to improve neurodevelopment, it is essential to ascertain whether
      pasteurized donor milk will confer the same advantage over formula without undue
      risks and at acceptable costs. Knowledge translation from this trial will be
      pivotal in setting donor milk policy in Canada and beyond. TRIAL REGISTRATION:
      ISRCTN35317141; Registered 10 August 2010.

PMID- 24884425
TI  - Workplace mental health: developing an integrated intervention approach.
AB  - BACKGROUND: Mental health problems are prevalent and costly in working
      populations. Workplace interventions to address common mental health problems
      have evolved relatively independently along three main threads or disciplinary
      traditions: medicine, public health, and psychology. In this Debate piece, we
      argue that these three threads need to be integrated to optimise the prevention
      of mental health problems in working populations. DISCUSSION: To realise the
      greatest population mental health benefits, workplace mental health intervention
      needs to comprehensively 1) protect mental health by reducing work-related risk
      factors for mental health problems; 2) promote mental health by developing the
      positive aspects of work as well as worker strengths and positive capacities; and
      3) address mental health problems among working people regardless of cause. We
      outline the evidence supporting such an integrated intervention approach and
      consider the research agenda and policy developments needed to move towards this
      goal, and propose the notion of integrated workplace mental health literacy.
      SUMMARY: An integrated approach to workplace mental health combines the strengths
      of medicine, public health, and psychology, and has the potential to optimise
      both the prevention and management of mental health problems in the workplace.

PMID- 24884426
TI  - Organellar genomes of the four-toothed moss, Tetraphis pellucida.
AB  - BACKGROUND: Mosses are the largest of the three extant clades of gametophyte
      dominant land plants and remain poorly studied using comparative genomic methods.
      Major monophyletic moss lineages are characterised by different types of a spore
      dehiscence apparatus called the peristome, and the most important unsolved
      problem in higher-level moss systematics is the branching order of these
      peristomate clades. Organellar genome sequencing offers the potential to resolve
      this issue through the provision of both genomic structural characters and a
      greatly increased quantity of nucleotide substitution characters, as well as to
      elucidate organellar evolution in mosses. We publish and describe the chloroplast
      and mitochondrial genomes of Tetraphis pellucida, representative of the most
      phylogenetically intractable and morphologically isolated peristomate lineage.
      RESULTS: Assembly of reads from Illumina SBS and Pacific Biosciences RS
      sequencing reveals that the Tetraphis chloroplast genome comprises 127,489 bp and
      the mitochondrial genome 107,730 bp. Although genomic structures are similar to
      those of the small number of other known moss organellar genomes, the chloroplast
      lacks the petN gene (in common with Tortula ruralis) and the mitochondrion has
      only a non-functional pseudogenised remnant of nad7 (uniquely amongst known moss
      chondromes). CONCLUSIONS: Structural genomic features exist with the potential to
      be informative for phylogenetic relationships amongst the peristomate moss
      lineages, and thus organellar genome sequences are urgently required for
      exemplars from other clades. The unique genomic and morphological features of
      Tetraphis confirm its importance for resolving one of the major questions in land
      plant phylogeny and for understanding the evolution of the peristome, a likely
      key innovation underlying the diversity of mosses. The functional loss of nad7
      from the chondrome is now shown to have occurred independently in all three
      bryophyte clades as well as in the early-diverging tracheophyte Huperzia
      squarrosa.

PMID- 24884428
TI  - Personality dimensions of schizophrenia patients compared to control subjects by
      gender and the relationship with illness severity.
AB  - BACKGROUND: Personality traits and schizophrenia present gender differences;
      however, gender has not been considered in most studies on personality and
      schizophrenia. This study aims to identify the different personality dimensions
      of schizophrenia patients and healthy control subjects by gender and to explore
      the relationship between personality dimensions and illness severity variables by
      analyzing data for males and females separately. METHODS: Temperament and
      Character Inventory-Revised dimensions were compared by gender between 161
      schizophrenia patients and 214 healthy controls from a population-based sample
      using independent t-tests. We then investigated whether personality dimensions
      are related to illness severity variables using correlation analyses and
      bivariate logistic regression, also by gender. RESULTS: The patients had
      significantly higher scores for harm avoidance (HA) and self-transcendence (ST)
      and lower scores for reward dependence (RD), cooperativeness (C), and self
      directedness (SD) than the controls. Similar results were obtained when the
      sample was stratified by gender, however the differences were higher and more
      significant for HA among males and for RD among females. The number of admissions
      to a psychiatric hospital positively correlated with novelty seeking (NS) in
      males and negatively with SD in females. In males, SD and ST negatively
      correlated with the number of suicide attempts. CONCLUSIONS: Male and female
      patients present difficulties for regulating and adapting behavior to achieve
      goals (SD) and for identifying and accepting others (C), as well as a great sense
      of spirituality and universe identification (ST). However, male patients are more
      characterized by being fearful, doubtful and easily fatigued (HA), while female
      patients are characterized by presenting difficulties maintaining and pursuing
      associated reward behaviors (RD). Furthermore, male and female patients who are
      frequently admitted to psychiatric hospitals and male patients who attempt
      suicide should be evaluated regarding their personality dimensions. Future
      studies assessing the relationship between personality dimensions and the
      clinical features of schizophrenia should consider gender differences.

PMID- 24884429
TI  - In absence of local adaptation, plasticity and spatially varying selection rule:
      a view from genomic reaction norms in a panmictic species (Anguilla rostrata).
AB  - BACKGROUND: American eel (Anguilla rostrata) is one of the few species for which
      panmixia has been demonstrated at the scale of the entire species. As such, the
      development of long term local adaptation is impossible. However, both plasticity
      and spatially varying selection have been invoked in explaining how American eel
      may cope with an unusual broad scope of environmental conditions. Here, we
      address this question through transcriptomic analyses and genomic reaction norms
      of eels from two geographic origins reared in controlled environments. RESULTS:
      The null hypothesis of no difference in gene expression between eels from the two
      origins was rejected. Many unique transcripts and two out of seven gene clusters
      showed significant difference in expression, both at time of capture and after
      three months of common rearing. Differences in expression were observed at
      numerous genes representing many functional groups when comparing eels from a
      same origin reared under different salinity conditions. Plastic response to
      different rearing conditions varied among gene clusters with three clusters
      showing significant origin-environment interactions translating into differential
      genomic norms of reaction. Most genes and functional categories showing
      differences between origins were previously shown to be differentially expressed
      in a study comparing transcription profiles between adult European eels
      acclimated to different salinities. CONCLUSIONS: These results emphasize that
      while plasticity in expression may be important, there is also a role for local
      genetic (and/or epigenetic) differences in explaining differences in gene
      expression between eels from different geographic origins. Such differences match
      those reported in genetically distinct populations in other fishes, both in terms
      of the proportion of genes that are differentially expressed and the diversity of
      biological functions involved. We thus propose that genetic differences between
      glass eels of different origins caused by spatially varying selection due to
      local environmental conditions translates into transcriptomic differences
      (including different genomic norms of reaction) which may in turn explain part of
      the phenotypic variance observed between different habitats colonized by eels.

PMID- 24884430
TI  - Depigmented-polymerised allergoids favour regulatory over effector T cells:
      enhancement by 1alpha, 25-dihydroxyvitamin D3.
AB  - BACKGROUND: Allergen immunotherapy (SIT) is the only treatment for allergic
      disease capable of modifying disease long term. To reduce the risk of anaphylaxis
      from SIT, allergen-extracts have been modified by polymerisation with
      glutaraldehyde to reduce IgE binding. It is suggested that these allergoid
      extracts also have reduced T cell activity, which could compromise clinical
      efficacy. Effective SIT is thought to act through regulatory T cells (Tregs)
      rather than activation of effector T cells. There is no published data on the
      activity of modified extracts on Tregs. RESULTS: We compared the capacity of
      modified (depigmented-polymerised) versus unmodified (native) allergen extracts
      of grass pollen and house dust mite to stimulate proliferation/cytokine
      production and to modulate Treg/effector T cell frequency in cultures of
      peripheral blood mononuclear cells (PBMC), from volunteers sensitised to both
      allergens in vitro. Depigmented-polymerised allergen extracts stimulated less
      proliferation of PBMC, and reduced effector cell numbers after 7 days in culture
      than did native extracts. However, the frequency of Foxp3+ Tregs in cultures were
      similar to those seen with native extract so that ratios of regulatory to
      effector T cells were significantly increased in cultures stimulated with
      depigmented-polymerised extracts. Addition of 1alpha, 25-dihydroxyvitamin D3
      further favoured Treg, and reduced effector cytokine production, but not
      interleukin-10. CONCLUSIONS: Depigmented-polymerised allergen extracts appear to
      favour Treg expansion over activation of effector T cells and this may relate to
      their demonstrated efficacy and safety in SIT. 1alpha, 25-dihydroxyvitamin D3
      further reduces effector T cell activation by allergen extracts and may be a
      useful adjuvant for SIT.

PMID- 24884431
TI  - Introducing rapid oral-fluid HIV testing among high risk populations in Shandong,
      China: feasibility and challenges.
AB  - BACKGROUND: This study was conducted to ascertain the feasibility of using rapid
      oral fluid testing as an alternative HIV testing method in China. METHOD: This is
      a mixed-method study among men who have sex with men (MSM), female sex workers
      (FSW) and VCT clients, conducted in 4 cities in Shandong Province. A pre-tested
      questionnaire was administered to 1137 participants through face-to-face
      interview to assess demographic characteristics, HIV testing histories and
      willingness to accept rapid oral fluid testing. VCT clients were provided with
      the saliva test kits for a screening test and errors in operation were recorded.
      Testing results were compared between oral and blood testing. Short feedback
      questionnaire was administered to 200 FSW who had undergone oral testing.
      RESULTS: The rate of willingness to take oral-fluid HIV testing among MSM, FSW
      and VCT clients was 72.8%, 72.1% and 67.4% respectively. Common errors recorded
      during test kit operation by the 229 VCT clients included: unpreparedness, wrong
      swab sampling, wrong dilution, wrong testing and inability to read test results.
      Advantages of oral testing listed by participants included: less intrusive,
      painlessness, easy self- testing and privacy. Disadvantages included perceived
      unreliable results (55.5%) and not nationally recognised (9%). Comparison of
      saliva and the blood testing results recorded a consistency rate of 0.970 (chi2 =
      153.348, P < 0.001), implying an excellent consistency. CONCLUSION: Introduction
      of oral rapid fluid testing as an alternative HIV testing method in China is
      highly feasible but with some challenges including low recognition and operation
      errors.

PMID- 24884433
TI  - Knowledge, attitudes, beliefs and behaviours of older adults about pneumococcal
      immunization, a Public Health Agency of Canada/Canadian Institutes of Health
      Research Influenza Research Network (PCIRN) investigation.
AB  - BACKGROUND: Fewer Canadian seniors are vaccinated against pneumococcal disease
      than receive the influenza vaccine annually. Improved understanding of factors
      influencing pneumococcal vaccination among older adults is needed to improve
      vaccine uptake. METHODS: A self-administered survey measuring knowledge,
      attitudes, beliefs and behaviours about pneumococcal vaccination was administered
      to a cohort of seniors participating in a clinical trial of seasonal influenza
      vaccines at eight centers across Canada. Eligible participants were ambulatory
      adults 65 years of age or older, in good health or with stable health conditions,
      previously given influenza vaccine. The primary outcome was self-reported receipt
      of pneumococcal vaccination. Multi-variable logistic regression was used to
      determine factors significantly associated with pneumococcal vaccine receipt.
      RESULTS: A total of 863 participants completed questionnaires (response rate
      92%); 58% indicated they had received the pneumococcal vaccine. Being offered the
      vaccine by a health care provider had the strongest relationship with vaccine
      receipt (AOR 23.4 (95% CI 13.4-40.7)). Other variables that remained
      significantly associated with vaccine receipt in the multivariable model included
      having heard of the vaccine (AOR 10.1(95% CI 4.7-21.7)), and strongly agreeing
      that it is important for adults > 65 to be vaccinated against pneumococcus (AOR
      3.3 (95% CI 1.2-9.2)). Participants who were < 70 years of age were less likely
      to be vaccinated. CONCLUSIONS: These results indicate healthcare recommendation
      significantly influenced vaccine uptake in this population of older adults.
      Measures to encourage healthcare providers to offer the vaccine may help increase
      coverage.

PMID- 24884434
TI  - High fluoride water in Bondo-Rarieda area of Siaya County, Kenya: a hydro
      geological implication on public health in the Lake Victoria Basin.
AB  - BACKGROUND: Only a few studies to evaluate groundwater fluoride in Eastern Africa
      have been undertaken outside the volcanic belt of the Great Eastern Africa Rift
      Valley. The extent and impact of water fluoride outside these regions therefore
      remain unclear. The current study evaluated fluoride levels in household water
      sources in Bondo-Rarieda Area in the Kenyan part of the Lake Victoria Basin (LVB)
      and highlighted the risk posed by water fluoride to the resident communities. The
      results, it was anticipated, will contribute to in-depth understanding of the
      fluoride problem in the region. METHODS: A total of 128 water samples were
      collected from different water sources from the entire study area and analyzed
      for fluoride content using ion-selective electrodes. RESULTS: Lake Victoria was
      the main water source in the area but dams and open pans (39.5%), boreholes and
      shallow wells (23.5%), and streams (18.5%) were the principal water sources
      outside walking distances from the lake. The overall mean fluoride content of the
      water exceeded recommended limits for drinking water. The mean water fluoride was
      highest in Uyoma (1.39+/-0.84 ppm), Nyang'oma (1.00+/-0.59 ppm) and Asembo
      (0.92+/-0.46 ppm) and lowest in Maranda Division (0.69+/-0.42 ppm). Ponds (1.41+/
      0.82 ppm), springs (1.25+/-0.43 ppm), dams and open pans (0.96+/-0.79 ppm), and
      streams (0.95+/-0.41 ppm) had highest fluoride levels but lake and river water
      did not have elevated fluoride levels. Groundwater fluoride decreased with
      increasing distance from the lake indicating that water fluoride may have hydro
      geologically been translocated into the region from geochemical sources outside
      the area. CONCLUSIONS: Lake Victoria was the main water source for the residents
      of Bondo-Rarieda Area. Majority of in-land residents however used water from
      dams, open pans, boreholes, shallow wells, ponds and streams, which was generally
      saline and fluoridated. It was estimated that 36% of children living in this
      area, who consume water from ground sources from the area could be at the risk of
      dental fluorosis.

PMID- 24884435
TI  - The contribution of media analysis to the evaluation of environmental
      interventions: the commuting and health in Cambridge study.
AB  - BACKGROUND: Media content can increase awareness of, and shape interactions with,
      public health interventions. As part of a natural experimental evaluation of the
      travel, physical activity and health impacts of the Cambridgeshire Guided Busway,
      we analysed print and social media discourse and interview data to understand the
      nature of new transport infrastructure and how it was experienced. METHODS:
      Newspaper articles were systematically retrieved from the LexisNexis database and
      tweets were identified from an online archive. Interviews were conducted as part
      of the larger evaluation study with 38 adults. Inductive thematic analysis was
      performed and comparisons were drawn between datasets. RESULTS: The findings are
      discussed in relation to five themes. First, an understanding of the intervention
      context and how the intervention was experienced was developed through accounts
      of events occurring pre and post the busway's opening. Second, the media captured
      the dynamic nature of the intervention. Third, the media constructed idealised
      portrayals of the anticipated busway which in some cases were contradicted by the
      impact of the busway on the existing context and people's lived experiences.
      Fourth, differential media coverage of the intervention components suggested that
      a lesser value was placed on promoting active travel compared with public
      transport. Lastly, interview data provided support for the hypothesis that the
      media increased awareness of the busway and served as a frame of reference for
      constructing expectations and comparing experiences. CONCLUSIONS: This analysis
      has contributed to the wider evaluation of the busway, helping to understand its
      nature and implementation and informing hypotheses about how the local population
      interact with the infrastructure by attending to the significance of
      representations in the media.

PMID- 24884436
TI  - Chronic alcohol consumption from adolescence-to-adulthood in mice--hypothalamic
      gene expression changes in the dilated cardiomyopathy signaling pathway.
AB  - BACKGROUND: Adolescence is a developmental stage vulnerable to alcohol drinking
      related problems and the onset of alcoholism. Hypothalamus is a key brain region
      for food and water intake regulation, and is one of the alcohol-sensitive brain
      regions. However, it is not known what would be the alcohol effect on
      hypothalamus following adolescent alcohol intake, chronically over the adolescent
      development, at moderate levels. RESULTS: We employed a paradigm of chronic
      moderate alcohol intake from adolescence-to-adulthood in mice, and analyzed the
      alcohol effect on both behavioral and hypothalamic gene expression changes. A
      total of 751 genes were found and subjected to pathway analysis. The dilated
      cardiomyopathy (DCM) pathway was identified. The changes of ten genes under this
      pathway were further verified using RT-PCR. Chronic alcohol consumption during
      adolescence, even at moderate levels, led to a decrease of motor activity in
      mice, and also a concerted down regulation of signaling pathway initiating factor
      (SPIF) genes in the DCM signaling pathway, including beta1-adrenergic receptor
      (Adrb1), Gs protein (Gnas), adenylyl cyclase 1 (Adcy1), and dihydropyridine
      receptor/L-type calcium channel (Cacna1d). CONCLUSIONS: These findings suggest
      that adolescent alcohol intake may trigger gene expression changes in the CNS
      that parallel those found in the dilated cardiomyopathy signaling pathway. If
      such effects also take place in humans, our findings would serve as a warning
      against alcohol intake in youth, such as by teens and/or college students.

PMID- 24884438
TI  - Growth attenuation under saline stress is mediated by the heterotrimeric G
      protein complex.
AB  - BACKGROUND: Plant growth is plastic, able to rapidly adjust to fluctuation in
      environmental conditions such as drought and salinity. Due to long-term
      irrigation use in agricultural systems, soil salinity is increasing; consequently
      crop yield is adversely affected. It is known that salt tolerance is a
      quantitative trait supported by genes affecting ion homeostasis, ion transport,
      ion compartmentalization and ion selectivity. Less is known about pathways
      connecting NaCl and cell proliferation and cell death. Plant growth and cell
      proliferation is, in part, controlled by the concerted activity of the
      heterotrimeric G-protein complex with glucose. Prompted by the abundance of
      stress-related, functional annotations of genes encoding proteins that interact
      with core components of the Arabidopsis heterotrimeric G protein complex (AtRGS1,
      AtGPA1, AGB1, and AGG), we tested the hypothesis that G proteins modulate plant
      growth under salt stress. RESULTS: Na+ activates G signaling as quantitated by
      internalization of Arabidopsis Regulator of G Signaling protein 1 (AtRGS1).
      Despite being components of a singular signaling complex loss of the Gbeta
      subunit (agb1-2 mutant) conferred accelerated senescence and aborted development
      in the presence of Na+, whereas loss of AtRGS1 (rgs1-2 mutant) conferred Na+
      tolerance evident as less attenuated shoot growth and senescence. Site-directed
      changes in the Galpha and Gbetagamma protein-protein interface were made to
      disrupt the interaction between the Galpha and Gbetagamma subunits in order to
      elevate free activated Galpha subunit and free Gbetagamma dimer at the plasma
      membrane. These mutations conferred sodium tolerance. Glucose in the growth media
      improved the survival under salt stress in Col but not in agb1-2 or rgs1-2
      mutants. CONCLUSIONS: These results demonstrate a direct role for G-protein
      signaling in the plant growth response to salt stress. The contrasting phenotypes
      of agb1-2 and rgs1-2 mutants suggest that G-proteins balance growth and death
      under salt stress. The phenotypes of the loss-of-function mutations prompted the
      model that during salt stress, G activation promotes growth and attenuates
      senescence probably by releasing ER stress.

PMID- 24884439
TI  - Identification of leptospiral 3-hydroxyacyl-CoA dehydrogenase released in the
      urine of infected hamsters.
AB  - BACKGROUND: Leptospirosis is a global zoonosis caused by pathogenic Leptospira.
      The non-specific clinical signs and symptoms of leptospirosis lead to its
      misdiagnosis. To date, there is still no reliable rapid test kit that can
      accurately diagnose leptospirosis at bedside or in field. In this research, with
      the ultimate goal of formulating a rapid and accurate diagnostic tool for
      leptospirosis, we aimed to identify leptospiral proteins excreted in urine of
      infected hamsters, which are thought to mimic Weil's disease. RESULTS: Hamsters
      were subcutaneously infected with leptospires, and the general attributes of
      urine as well as the proteins excreted in it were examined. Some leptospiral
      proteins were found to be excreted in the urine from the early phase of
      infection. The most important finding of this study was the detection of the
      lipid-metabolizing enzyme, 3-hydroxyacyl-CoA dehydrogenase (HADH), before the
      onset of illness, when leptospires were not yet detected in the urine of infected
      hamsters. CONCLUSIONS: This is the first report on the detection of leptospiral
      HADH in the host urine, which may be a possible candidate leptospiral antigen
      that can be used in the early diagnosis of human and animal leptospirosis.

PMID- 24884440
TI  - Physical inactivity is strongly associated with anxiety and depression in Iraqi
      immigrants to Sweden: a cross-sectional study.
AB  - BACKGROUND: Increasing evidence on associations between mental health and chronic
      diseases like cardio-vascular disease and diabetes together with the fact that
      little is known about the prevalence of anxiety/depression and associated risk
      factors among Iraqi immigrants to Sweden, warrants a study in this group. The aim
      was to study the prevalence of anxiety and depression in immigrants from Iraq
      compared to native Swedes and compare socioeconomic and lifestyle-related factors
      associated with these conditions. METHOD: A population-based, cross-sectional
      study of residents of Malmo, Sweden, aged 30-75 years, born in Iraq or Sweden.
      The overall response rate was 49% for Iraqis and 32% for Swedes. Anxiety and
      depression were assessed using the Hospital Anxiety and Depression Scale.
      Associations were studied using multivariate logistic regression models. The
      outcome was odds of depression and/or anxiety. RESULTS: Compared to Swedes (n =
      634), anxiety was three times as prevalent (52.6 vs. 16.3%, p < 0.001) and
      depression five times as prevalent (16.3 vs. 3.1%, p < 0.001) in Iraqi immigrants
      (n = 1255). Iraqis were three times more likely to be anxious and/or depressed
      compared to Swedes (odds ratio (OR) 3.02, 95% confidence interval (CI) 2.06
      4.41). Among Iraqis, physical inactivity (<150 min/week) (OR 2.00, 95% CI 1.49
      2.69), economic insecurity (OR 2.16, 95% CI 1.56-3.01), inability to trust people
      (OR 1.75, 95% CI 1.28-2.39) and smoking (OR 1.43, 95% CI 1.02-2.01), were
      strongly associated with anxiety/depression. Among Swedes, living alone (OR 2.10,
      95% CI 1.36-3.25) and economic insecurity (OR 2.38, 95% CI 1.38-4.12) showed the
      strongest associations with anxiety/depression. Country of birth modified the
      effect of physical inactivity (P(interaction) =0.058) as well as of marital
      status (P(interaction) =0.001). CONCLUSION: Our study indicates that economic
      insecurity has a major impact on poor mental health irrespective of ethnic
      background but that physical inactivity may be more strongly associated with
      anxiety/depression in immigrants from the Middle East compared to native Swedes.
      Preventive actions emphasizing increased physical activity may reduce the risk of
      poor mental health in immigrants from the Middle East, however intervention
      studies are warranted to test this hypothesis.

PMID- 24884442
TI  - Direct characterization of plasmonic slot waveguides and nanocouplers.
AB  - We demonstrate the use of amplitude- and phase-resolved near-field mapping for
      direct characterization of plasmonic slot waveguide mode propagation and
      excitation with nanocouplers in the telecom wavelength range. We measure mode's
      propagation length, effective index and field distribution and directly evaluate
      the relative coupling efficiencies for various couplers configurations. We report
      26- and 15-fold improvements in the coupling efficiency with two serially
      connected dipole and modified bow-tie antennas, respectively, as compared to that
      of the short-circuited waveguide termination. 

PMID- 24884441
TI  - Exploring the evolutionary route of the acquisition of betaine aldehyde
      dehydrogenase activity by plant ALDH10 enzymes: implications for the synthesis of
      the osmoprotectant glycine betaine.
AB  - BACKGROUND: Plant ALDH10 enzymes are aminoaldehyde dehydrogenases (AMADHs) that
      oxidize different omega-amino or trimethylammonium aldehydes, but only some of
      them have betaine aldehyde dehydrogenase (BADH) activity and produce the
      osmoprotectant glycine betaine (GB). The latter enzymes possess alanine or
      cysteine at position 441 (numbering of the spinach enzyme, SoBADH), while those
      ALDH10s that cannot oxidize betaine aldehyde (BAL) have isoleucine at this
      position. Only the plants that contain A441- or C441-type ALDH10 isoenzymes
      accumulate GB in response to osmotic stress. In this work we explored the
      evolutionary history of the acquisition of BAL specificity by plant ALDH10s.
      RESULTS: We performed extensive phylogenetic analyses and constructed and
      characterized, kinetically and structurally, four SoBADH variants that simulate
      the parsimonious intermediates in the evolutionary pathway from I441-type to A441
      or C441-type enzymes. All mutants had a correct folding, average thermal
      stabilities and similar activity with aminopropionaldehyde, but whereas A441S and
      A441T exhibited significant activity with BAL, A441V and A441F did not. The
      kinetics of the mutants were consistent with their predicted structural features
      obtained by modeling, and confirmed the importance of position 441 for BAL
      specificity. The acquisition of BADH activity could have happened through any of
      these intermediates without detriment of the original function or protein
      stability. Phylogenetic studies showed that this event occurred independently
      several times during angiosperms evolution when an ALDH10 gene duplicate changed
      the critical Ile residue for Ala or Cys in two consecutive single mutations.
      ALDH10 isoenzymes frequently group in two clades within a plant family: one
      includes peroxisomal I441-type, the other peroxisomal and non-peroxisomal I441-,
      A441- or C441-type. Interestingly, high GB-accumulators plants have non
      peroxisomal A441- or C441-type isoenzymes, while low-GB accumulators have the
      peroxisomal C441-type, suggesting some limitations in the peroxisomal GB
      synthesis. CONCLUSION: Our findings shed light on the evolution of the synthesis
      of GB in plants, a metabolic trait of most ecological and physiological relevance
      for their tolerance to drought, hypersaline soils and cold. Together, our results
      are consistent with smooth evolutionary pathways for the acquisition of the BADH
      function from ancestral I441-type AMADHs, thus explaining the relatively high
      occurrence of this event.

PMID- 24884443
TI  - The community and consumer food environment and children's diet: a systematic
      review.
AB  - BACKGROUND: While there is a growing body of research on food environments for
      children, there has not been a published comprehensive review to date evaluating
      food environments outside the home and school and their relationship with diet in
      children. The purpose of this paper is to review evidence on the influence of the
      community and consumer nutrition environments on the diet of children under the
      age of 18 years. METHODS: Our search strategy included a combination of both
      subject heading searching as well as natural language, free-text searching. We
      searched nine databases (MEDLINE, Web of Science, CINAHL, Embase, Scopus,
      ProQuest Public Health, PsycINFO, Sociological Abstracts, and GEOBASE) for papers
      published between 1995 and July 2013. Study designs were included if they were
      empirically-based, published scholarly research articles, were focused on
      children as the population of interest, fit within the previously mentioned date
      range, included at least one diet outcome, and exposures within the community
      nutrition environment (e.g., location and accessibility of food outlets), and
      consumer nutrition environment (e.g., price, promotion, and placement of food
      choices). RESULTS: After applying exclusion and inclusion criteria, a total of 26
      articles were included in our review. The vast majority of the studies were cross
      sectional in design, except for two articles reporting on longitudinal studies.
      The food environment exposure(s) included aspects of the community nutrition
      environments, except for three that focused on the consumer nutrition
      environment. The community nutrition environment characterization most often used
      Geographic Information Systems to geolocate participants' homes (and/or schools)
      and then one or more types of food outlets in relation to these. The children
      included were all of school age. Twenty-two out of 26 studies showed at least one
      positive association between the food environment exposure and diet outcome. Four
      studies reported only null associations. CONCLUSIONS: This review found moderate
      evidence of the relationship between the community and consumer nutrition
      environments and dietary intake in children up to 18 years of age. There is wide
      variation in measures used to characterize both the community and consumer
      nutrition environments and diet, and future research should work to decrease this
      heterogeneity.

PMID- 24884446
TI  - Supporting intensive interventions for students with autism spectrum disorder:
      performance feedback and discrete trial teaching.
AB  - This study evaluated the impact of performance feedback on nine public educators'
      level of procedural integrity to Discrete Trial Teaching (DTT) procedures for
      students with Autism Spectrum Disorder (ASD). Procedural integrity was observed
      during four phases: no feedback, general feedback, performance feedback, and
      maintenance, in a multiple baseline across participants design. Results indicate
      that for most educators, performance feedback is necessary to improve and
      maintain integrity at or above 80%. Most participants' performance during no
      feedback and general feedback was characterized by high rates of variability. One
      participant required in vivo feedback to achieve and maintain acceptable levels
      of integrity. Procedural modifications necessary to adapt this procedure to the
      applied environment of school are discussed. Findings suggest that highly
      structured evidence-based interventions for students with ASD require
      consultation support to be implemented with integrity in schools, and the
      duration and intensity of support needed may be higher than for other
      interventions. These promising findings emphasize the important role of school
      psychologists and other support personnel in ensuring that services are delivered
      as intended.

PMID- 24884447
TI  - Life satisfaction and maladaptive behaviors in early adolescents.
AB  - This study explored the directionality of the relations between global life
      satisfaction (LS) and internalizing and externalizing behaviors using a sample of
      regular education students who were initially enrolled in Grade 7 (n = 470). Self
      report measures of internalizing and externalizing behaviors and LS were
      administered on 2 occasions, 6 months apart, to students from a Southeastern U.S.
      middle school. Short-term longitudinal analyses revealed that neither
      externalizing behaviors nor internalizing behaviors at Time 1 predicted LS at
      Time 2. However, LS at Time 1 predicted externalizing behaviors at Time 2. LS at
      Time 1 also predicted internalizing behaviors at Time 2, but the results were
      moderated by student gender. At higher levels of LS, boys reported lower levels
      of internalizing behaviors at Time 2. The overall results suggested that lower
      levels of LS are an antecedent of increased maladaptive behaviors among early
      adolescents. Alternatively, higher levels of LS may be a protective factor
      against subsequent externalizing behaviors among boys and girls and internalizing
      behaviors among boys. Furthermore, the results provide further support for the
      discriminant validity of positive and negative measures of mental health and
      suggest that LS measures may provide useful information for comprehensive
      adolescent health screening and monitoring systems.

PMID- 24884444
TI  - Accumulation of lifestyle and psychosocial problems and persistence of adverse
      lifestyle over two-year follow-up among Finnish adolescents.
AB  - BACKGROUND: Adolescent'psychosocial problems associate with unhealthy behaviors,
      but data on co-occurring patterns is sparse. We investigated 1) whether
      adolescents could be categorized into meaningful subgroups with respect to
      psychosocial and lifestyle factors, 2) whether the prevalence of physical
      inactivity, overweight and smoking vary within the subgroups and 3) whether these
      unhealthy behaviors persist in a two-year follow-up. METHODS: The study was based
      on a subgroup of the 1986 Northern Finland Birth Cohort, which consisted of
      adolescents who replied to a postal questionnaire at 16 years (n = 6792) and a
      subgroup of this sample at 18 years (n = 1552). Latent class analysis (LCA) was
      performed to establish clusters at 16 years. RESULTS: Smoking co-existed with
      emotional and behavioral problems in both genders. Boys with the most inactive
      lifestyle slept poorly, whereas multiple problems co-occurred among girls. Those
      with a high body mass index (BMI) separated as groups of their own. Different
      combinations of adverse lifestyle and emotional and behavioral problems were
      relatively common in both sexes as only 51% of boys and 67% of girls belonged to
      the reference cluster with low probability for these findings. Physical
      inactivity, high BMI and smoking tended to persist over the two-year follow-up.
      CONCLUSIONS: It seems that lifestyle and psychosocial factors divide adolescents
      into distinct subgroups in which unhealthy lifestyle patterns remain between the
      ages of 16 and 18. This may indicate problems in other life areas and expose them
      to an increased risk of future health problems.

PMID- 24884448
TI  - Multilevel multi-informant structure of the authoritative school climate survey.
AB  - The Authoritative School Climate Survey was designed to provide schools with a
      brief assessment of 2 key characteristics of school climate--disciplinary
      structure and student support--that are hypothesized to influence 2 important
      school climate outcomes--student engagement and prevalence of teasing and
      bullying in school. The factor structure of these 4 constructs was examined with
      exploratory and confirmatory factor analyses in a statewide sample of 39,364
      students (Grades 7 and 8) attending 423 schools. Notably, the analyses used a
      multilevel structural approach to model the nesting of students in schools for
      purposes of evaluating factor structure, demonstrating convergent and concurrent
      validity and gauging the structural invariance of concurrent validity
      coefficients across gender. These findings provide schools with a core group of
      school climate measures guided by authoritative discipline theory.

PMID- 24884449
TI  - Estimating intervention effects across different types of single-subject
      experimental designs: empirical illustration.
AB  - The purpose of this study is to illustrate the multilevel meta-analysis of
      results from single-subject experimental designs of different types, including AB
      phase designs, multiple-baseline designs, ABAB reversal designs, and alternating
      treatment designs. Current methodological work on the meta-analysis of single
      subject experimental designs often focuses on combining simple AB phase designs
      or multiple-baseline designs. We discuss the estimation of the average
      intervention effect estimate across different types of single-subject
      experimental designs using several multilevel meta-analytic models. We illustrate
      the different models using a reanalysis of a meta-analysis of single-subject
      experimental designs (Heyvaert, Saenen, Maes, & Onghena, in press). The
      intervention effect estimates using univariate 3-level models differ from those
      obtained using a multivariate 3-level model that takes the dependence between
      effect sizes into account. Because different results are obtained and the
      multivariate model has multiple advantages, including more information and
      smaller standard errors, we recommend researchers to use the multivariate
      multilevel model to meta-analyze studies that utilize different single-subject
      designs.

PMID- 24884450
TI  - Teacher Network of Relationships Inventory: measurement invariance of
      academically at-risk students across ages 6 to 15.
AB  - We tested the longitudinal measurement invariance of the Teacher Network of
      Relationships Inventory (TNRI), a teacher-report measure of teacher-student
      relationship quality (TSRQ), on a sample of 784 academically at-risk students
      across ages 6 to 15 years by comparing the model for each subsequent year with
      that of the previous year(s). The TNRI was constructed with 22 items to form 3
      correlated factors: Warmth, Conflict, and Intimacy. Cronbach's alphas ranged from
      .87 to .96 across 9 years. Both metric and scalar measurement invariance held for
      9 years, indicating that scores on the TNRI have similar meaning across these
      ages. The TNRI also demonstrated measurement invariance across gender and
      race/ethnicity. Findings support that the TNRI is an appropriate measure for
      investigating substantive issues related to developmental changes in TSRQ from
      early childhood through adolescence, including gender and ethnic/racial
      differences in TSRQ across these ages. Based on repeated-measures ANOVAs, each
      scale decreased across the 9 years, although the growth patterns for scales
      differed somewhat: Conflict had a linearly decreasing pattern, Warmth declined
      most notably as students make the transition to adolescence, whereas Intimacy
      scores dropped off noticeably at the transition from early to late childhood.
      Research limitations and implications for practice are discussed.

PMID- 24884451
TI  - A latent class growth analysis of school bullying and its social context: the
      self-determination theory perspective.
AB  - The contribution of social context to school bullying was examined from the self
      determination theory perspective in this longitudinal study of 536 adolescents
      from 3 secondary schools in Hong Kong. Latent class growth analysis of the
      student-reported data at 5 time points from grade 7 to grade 9 identified 4
      groups of students: bullies (9.8%), victims (3.0%), bully-victims (9.4%), and
      typical students (77.8%). There was a significant association between academic
      tracking and group membership. Students from the school with the lowest academic
      performance had a greater chance of being victims and bully-victims. Longitudinal
      data showed that all 4 groups tended to report less victimization over the years.
      The victims and the typical students also had a tendency to report less bullying
      over the years, but this tendency was reversed for bullies and bully-victims.
      Perceived support from teachers for relatedness significantly predicted
      membership of the groups of bullies and victims. Students with higher perceived
      support for relatedness from their teachers had a significantly lower likelihood
      of being bullies or victims. The findings have implications for the theory and
      practice of preventive interventions in school bullying.

PMID- 24884452
TI  - Disease knowledge level is a noteworthy risk factor of anxiety and depression in
      patients with chronic obstructive pulmonary disease: a cross-sectional study.
AB  - BACKGROUND: Risk factors of anxiety and depression symptoms in patients with
      chronic obstructive pulmonary disease (COPD) have been widely researched, but
      most of them cannot be addressed clinically. The aim of this study was to
      investigate whether COPD knowledge level is a risk factor of anxiety and/or
      depression in COPD patients in addition to functional capacity and quality of
      life, and to determine the key topics of COPD knowledge. METHODS: A total of 364
      COPD patients from four centers were recruited into this cross-sectional survey.
      Subjects' general medical information, assessments of lung function, dyspnea,
      quality of life, and exercise capacity, and responses to the Hospital Anxiety and
      Depression Scale (HAD) and the Bristol COPD Knowledge Questionnaire (BCKQ) were
      collected. Partial correlation analysis was performed, and a multivariable model
      testing risk factors of anxiety and depression as well as a multivariable model
      of 13 topics of knowledge derived from BCKQ were constructed. RESULTS: Subjects
      with anxiety or depression were more likely to have less COPD knowledge. Partial
      correlation analysis revealed that HAD score was negatively correlated with BCKQ
      score (rho = -0.153, P = 0.004). BCKQ score was significant in the multivariable
      model that tested risk factors of anxiety and depression (P = 0.001, OR = 0.944).
      Topics of epidemiology (P < 0.001, OR = 0.653) and infections (P = 0.006, OR =
      0.721) were significant in the multivariable model evaluating 13 topics.
      CONCLUSIONS: The level of patients' disease knowledge is a significant risk
      factor of anxiety and depression in COPD patients. Epidemiology and infections
      are key topics of COPD knowledge to target in the Chinese population. TRIAL
      REGISTRATION: ChiCTR-OCS-12002518.

PMID- 24884454
TI  - Safety of infusing rituximab at a more rapid rate in patients with rheumatoid
      arthritis: results from the RATE-RA study.
AB  - BACKGROUND: As recommended in the current prescribing information, rituximab
      infusions in patients with rheumatoid arthritis (RA) take 4.25 hours for the
      first infusion and 3.25 hours for subsequent infusions, which is a burden on
      patients and the health care system. We therefore evaluated the safety of
      infusing rituximab at a faster rate for an infusion period of 2 hours in patients
      with RA. METHODS: Patients with an inadequate response to anti-TNF who were
      rituximab-naive or -experienced received 2 courses of rituximab: Infusion 1 (Day
      1) was administered over the standard 4.25 hours, and Infusions 2 (Day 15), 3
      (Day 168) and 4 (Day 182) were administered over a faster 2-hour period. The
      primary endpoint was incidence of infusion-related reactions (IRRs) associated
      with Infusion 2. RESULTS: Of the 351 patients enrolled, 87% and 13% were
      rituximab-naive and -experienced, respectively. The incidence (95% CI) of IRRs
      associated with Infusion 1 was 16.2% (12.5%, 20.5%) and consistent with weighted
      historical incidence of 20.7% (19.4%, 22.1%). The incidence (95% CI) of IRRs
      associated with Infusions 2, 3, and 4 compared with respective weighted
      historical incidences at the standard infusion rate was 6.5% (4.1%, 9.7%) vs 8.1%
      (7.2%, 9.1%); 5.9% (3.5%, 9.3%) vs 11.5% (10.3%, 12.8%); and 0.7 (0.1%, 2.6%) vs
      5.0% (4.2%, 6.0%), respectively. All IRRs were grade 1 or 2, except for 3 grade 3
      IRRs associated with Infusion 1 and 2 grade 3 IRRs associated with Infusion 2.
      Four patients experienced a total of 5 grade 3 IRRs; 3 of these patients
      continued on to received subsequent infusions at the faster rate. There were no
      serious IRRs. CONCLUSION: This study demonstrated that rituximab can be
      administered at the faster infusion rate at the second and subsequent infusions
      without increasing the rate or severity of IRRs.

PMID- 24884455
TI  - Neuromuscular training and muscle strengthening in patients with patellofemoral
      pain syndrome: a protocol of randomized controlled trial.
AB  - BACKGROUND: Patellofemoral pain syndrome (PFPS) is a common musculoskeletal
      condition, particularly among women. Patients with PFPS usually experience
      weakness in the gluteal muscles, as well as pain and impaired motor control
      during activities of daily living. Strengthening the hip muscles is an effective
      way of treating this disorder. Neuromuscular training has also been identified as
      a therapeutic tool, although the benefits of this intervention in patients with
      PFPS patients remain inconclusive. DESIGN: This is a protocol of randomized
      controlled trial with a blind assessor. Thirty-four women with a clinical
      diagnosis of PFPS participated. These participants were allocated into two groups
      (experimental and control). The experimental group performed twelve sessions to
      strengthen the knee extensors, hip abductor and lateral rotator muscles in
      association with neuromuscular training of the trunk and lower extremities. The
      control group performed the same number of sessions to strengthen the muscles of
      the hip and knee. The primary outcome was functional capacity (Anterior Knee Pain
      Scale - AKPS) at 4 weeks. Pain intensity, muscle strength and kinematic changes
      were also measured during the step down test after four weeks of intervention.
      Follow up assessments were conducted after three and six months to assess
      functional capacity and pain. The effects of the treatment (i.e. between-group
      differences) were calculated using mixed linear models. DISCUSSION: The present
      study was initiated on the 1st of April 2013 and is currently in progress. The
      results of this study may introduce another effective technique of conservative
      treatment and could guide physical therapists in the clinical decision-making
      process for women with PFPS. TRIAL REGISTRATION: Current Controlled Trials
      NCT01804608.

PMID- 24884456
TI  - Effect of occipitocervical fusion with screw-rod system for upper cervical spine
      tumor.
AB  - BACKGROUND: Craniospinal junction tumors are rare but severe lesions. Surgical
      stabilization has been established to be an ideal treatment for upper cervical
      tumor pathology. The purpose of this study was to evaluate the effect of a screw
      rod system for occipitocervical fusion. METHODS: A total of 24 cases with C1 and
      C2 cervical tumor underwent occipitocervical fusion with Vertex screw-rod
      internal fixation from January 2005 to December 2012. Preoperative X-ray and MRI
      examinations were performed on all patients before the operation, after the
      operation, and during last follow-up. The JOA score was used to assess
      neurological function pre and postoperatively. RESULTS: All the patients were
      followed up for 6 to 42 months with an average of 24 months. The result of X-ray
      showed that bony fusion was successful in 18 patients at 3 months and 6 patients
      at 6 months of follow-ups. There was no deterioration of spinal cord injury. The
      JOA Scores of neurological function increased significantly. CONCLUSION: The
      screw-rod system offers strong fixation and good fusion for occipitocervical
      fusion. It is an effective and reliable method for reconstruction of upper
      cervical spine tumor.

PMID- 24884457
TI  - The promise of record linkage for assessing the uptake of health services in
      resource constrained settings: a pilot study from South Africa.
AB  - BACKGROUND: Health and Demographic Surveillance Systems (HDSS) have been
      instrumental in advancing population and health research in low- and middle-
      income countries where vital registration systems are often weak. However, the
      utility of HDSS would be enhanced if their databases could be linked with those
      of local health facilities. We assess the feasibility of record linkage in rural
      South Africa using data from the Agincourt HDSS and a local health facility.
      METHODS: Using a gold standard dataset of 623 record pairs matched by means of
      fingerprints, we evaluate twenty record linkage scenarios (involving different
      identifiers, string comparison techniques and with and without clerical review)
      based on the Fellegi-Sunter probabilistic record linkage model. Matching rates
      and quality are measured by their sensitivity and positive predictive value
      (PPV). Background characteristics of matched and unmatched cases are compared to
      assess systematic bias in the resulting record-linked dataset. RESULTS: A hybrid
      approach of deterministic followed by probabilistic record linkage, and scenarios
      that use an extended set of identifiers including another household member's
      first name yield the best results. The best fully automated record linkage
      scenario has a sensitivity of 83.6% and PPV of 95.1%. The sensitivity and PPV
      increase to 84.3% and 96.9%, respectively, when clerical review is undertaken on
      10% of the record pairs. The likelihood of being linked is significantly lower
      for females, non-South Africans and the elderly. CONCLUSION: Using records
      matched by means of fingerprints as the gold standard, we have demonstrated the
      feasibility of fully automated probabilistic record linkage using identifiers
      that are routinely collected in health facilities in South Africa. Our study also
      shows that matching statistics can be improved if other identifiers (e.g.,
      another household member's first name) are added to the set of matching
      variables, and, to a lesser extent, with clerical review. Matching success is,
      however, correlated with background characteristics that are indicative of the
      instability of personal attributes over time (e.g., surname in the case of women)
      or with misreporting (e.g., age).

PMID- 24884458
TI  - The relation of location-specific epicardial adipose tissue thickness and
      obstructive coronary artery disease: systemic review and meta-analysis of
      observational studies.
AB  - BACKGROUND: There is growing evidence about the importance of epicardial
      adiposity on cardiometabolic risk. However, the relation of location-specific
      epicardial adipose tissue (EAT) thickness to coronary atherosclerotic burden is
      still unclear. METHODS: This meta-analysis was used to study the relations
      between location-specific EAT thickness and obstructive coronary artery disease
      (CAD). A systemic literature search to identify eligible studies that met the
      inclusion criteria from the beginning until January 2014 was made. We conducted
      the meta-analysis of all included 10 published studies. Pre-specified subgroup
      analyses were performed according to ethnicity, body mass index, diagnostic tools
      for CAD, and measurement tool if presence of high heterogeneity between studies.
      Potential publication bias was also assessed. RESULTS: We identified ten observed
      studies with a total of 1625 subjects for planned comparison. With regard to the
      association between obstructive CAD and location-specific EAT thickness at the
      right ventricular free wall, caution is warranted. The pooled estimate showed
      that location-specific EAT thickness at the right ventricular free wall was
      significantly higher in the CAD group than non-CAD group (standardized mean
      difference (SMD): 0.70 mm, 95% CI: 0.26-1.13, P = 0.002), although heterogeneity
      was high (I2 = 93%). It should be clear that only the result of echocardiography
      based studies showed a significant association (SMD: 0.98 mm, 95% CI: 0.43-1.53,
      P = 0.0005), and the result of all included CT-based studies showed a non
      significant association (SMD: 0.06 mm, 95% CI: -0.12-0.25, P = 0.50). In the
      subgroup analysis, the "diagnostic tools for CAD" or "measurement tool of EAT
      thickness" are potential major sources of heterogeneity between studies. With
      regard to location-specific EAT thickness at the left atrioventricular (AV)
      groove, it was significantly higher in the CAD group than non-CAD group (SMD:
      0.74 mm, 95% CI: 0.55-0.92, P <0.00001; I2 = 0%). CONCLUSION: Our meta-analysis
      suggests that significantly elevated location-specific EAT thickness at the left
      AV groove is associated with obstructive CAD. Based on the current evidence, the
      location-specific EAT thickness at the left AV groove appears to be a good
      predictor in obstructive CAD, especially in Asian populations. Furthermore well
      designed studies are warranted because of the current limited number of studies.

PMID- 24884459
TI  - Recombinant fusion protein of cholera toxin B subunit with YVAD secreted by
      Lactobacillus casei inhibits lipopolysaccharide-induced caspase-1 activation and
      subsequent IL-1 beta secretion in Caco-2 cells.
AB  - BACKGROUND: Lactobacillus species are used as bacterial vectors to deliver
      functional peptides to the intestine because they are delivered live to the
      intestine, colonize the mucosal surface, and continue to produce the desired
      protein. Previously, we generated a recombinant Lactobacillus casei secreting the
      cholera toxin B subunit (CTB), which can translocate into intestinal epithelial
      cells (IECs) through GM1 ganglioside. Recombinant fusion proteins of CTB with
      functional peptides have been used as carriers for the delivery of these peptides
      to IECs because of the high cell permeation capacity of recombinant CTB (rCTB).
      However, there have been no reports of rCTB fused with peptides expressed or
      secreted by Lactobacillus species. In this study, we constructed L. casei
      secreting a recombinant fusion protein of CTB with YVAD (rCTB-YVAD). YVAD is a
      tetrapeptide (tyrosine-valine-alanine-aspartic acid) that specifically inhibits
      caspase-1, which catalyzes the production of interleukin (IL)-1beta, an
      inflammatory cytokine, from its inactive precursor. Here, we examined whether
      rCTB-YVAD secreted by L. casei binds to GM1 ganglioside and inhibits caspase-1
      activation in Caco-2 cells used as a model of IECs. RESULTS: We constructed the
      rCTB-YVAD secretion vector pSCTB-YVAD by modifying the rCTB secretion vector
      pSCTB. L. casei secreting rCTB-YVAD was generated by transformation with pSCTB
      YVAD. Both the culture supernatant of pSCTB-YVAD-transformed L. casei and
      purified rCTB-YVAD bound to GM1 ganglioside, as did the culture supernatant of
      pSCTB-transformed L. casei and purified rCTB. Interestingly, although both
      purified rCTB-YVAD and rCTB translocated into Caco-2 cells, regardless of
      lipopolysaccharide (LPS), only purified rCTB-YVAD but not rCTB inhibited LPS
      induced caspase-1 activation and subsequent IL-1beta secretion in Caco-2 cells,
      without affecting cell viability. CONCLUSIONS: The rCTB protein fused to a
      functional peptide secreted by L. casei can bind to GM1 ganglioside, like rCTB,
      and recombinant YVAD secreted by L. casei may exert anti-inflammatory effects in
      the intestine. Therefore, rCTB secreted by L. casei has potential utility as a
      vector for the delivery of YVAD to IECs.

PMID- 24884460
TI  - Gaining information about home visits in primary care: methodological issues from
      a feasibility study.
AB  - BACKGROUND: Home visits are part of general practice work in Germany. Within the
      context of an expanding elderly population and a decreasing number of general
      practitioner (GPs), open questions regarding the organisation and adequacy of
      GPs' care in immobile patients remain. To answer these questions, we will conduct
      a representative primary data collection concerning contents and organisation of
      GPs' home visits in 2014. Because this study will require considerable efforts
      for documentation and thus substantial involvement by participating GPs, we
      conducted a pilot study to see whether such a study design was feasible. METHODS:
      We used a mixed methods design with two study arms in a sample of teaching GPs of
      the University Halle. The quantitative arm evaluates participating GPs and
      documentation of home visits. The qualitative arm focuses on reasons for non
      participation for GPs who declined to take part in the pilot study. RESULTS: Our
      study confirms previously observed reasons for non-response of GPs in the
      particular setting of home visits including lack of time and/or interest. In
      contrast to previous findings, monetary incentives were not crucial for GPs
      participation. Several factors influenced the documentation rate of home visits
      and resulted in a discrepancy between the numbers of home visits documented
      versus those actually conducted. The most frequently reported problem was related
      to obtaining patient consent, especially when patients were unable to provide
      informed consent due to cognitive deficits. CONCLUSIONS: The results of our
      feasibility study provide evidence for improvement of the study design and study
      instruments to effectively conduct a documentation-intensive study of GPs doing
      home visits. Improvement of instructions and questionnaire regarding time
      variables and assessment of the need for home visits will be carried out to
      increase the reliability of future data. One particularly important
      methodological issue yet to be resolved is how to increase the representativeness
      of home visit care by including the homebound patient population that is unable
      to provide informed consent.

PMID- 24884461
TI  - Contraceptive-induced amenorrhoea leads to reduced migraine frequency in women
      with menstrual migraine without aura.
AB  - BACKGROUND: Menstrual migraine without aura (MM) affects approximately 20% of
      female migraineurs in the general population. The aim of the present study was to
      investigate the influence of contraception on the attacks of migraine without
      aura (MO) in women with MM. FINDINGS: 141 women from the general population with
      a history of MM according to the International Classification of Headache
      Disorders II (ICHD II) were interviewed by a headache specialist. Of 49 women
      with a history of MM currently using hormonal contraception, 23 reported
      amenorrhoea. Significantly more women with amenorrhoea reported no MO- days
      during the preceding month compared to women without amenorrhoea (OR 16.1; 95%
      confidence interval (CI) 1.8-140.4; P = 0.003). A reduction of MO-frequency was
      more often reported in women with than without amenorrhoea (OR 3.5; 95% CI 1.1
      11.4; P = 0.04). CONCLUSION: Amenorrhoea leads to a reduction of MO-frequency in
      women with MM using hormonal contraceptives. Future prospective studies on MM
      should focus on contraceptive methods that achieve amenorrhoea.

PMID- 24884462
TI  - Valproate pretreatment protects pancreatic beta-cells from palmitate-induced ER
      stress and apoptosis by inhibiting glycogen synthase kinase-3beta.
AB  - BACKGROUND: Reduction of pancreatic beta-cells mass, major secondary to increased
      beta-cells apoptosis, is increasingly recognized as one of the main contributing
      factors to the pathogenesis of type 2 diabetes (T2D), and saturated free fatty
      acid palmitate has been shown to induce endoplasmic reticulum (ER) stress that
      may contribute to promoting beta-cells apoptosis. Recent literature suggests that
      valproate, a diffusely prescribed drug in the treatment of epilepsy and bipolar
      disorder, can inhibit glycogen synthase kinase-3beta (GSK-3beta) activity and has
      cytoprotective effects in neuronal cells and HepG2 cells. Thus, we hypothesized
      that valproate may protect INS-1 beta-cells from palmitate-induced apoptosis via
      inhibiting GSK-3beta. RESULTS: Valproate pretreatment remarkable prevented
      palmitate-mediated cytotoxicity and apoptosis (lipotoxicity) as well as ER
      distension. Furthermore, palmitate triggered ER stress as evidenced by increased
      mRNA levels of C/EBP homologous protein (CHOP) and activating transcription
      factor 4 (ATF4) in a time-dependent fashion. However, valproate not only reduced
      the mRNA and protein expression of CHOP but also inhibited GSK-3beta and caspase
      3 activity induced by palmitate, whereas, the mRNA expression of ATF4 was not
      affected. Interestingly, TDZD-8, a specific GSK-3beta inhibitor, also showed the
      similar effect on lipotoxicity and ER stress as valproate in INS-1 cells.
      Finally, compared with CHOP knockdown, valproate displayed better cytoprotection
      against palmitate. CONCLUSIONS: Valproate may protect beta-cells from palmitate
      induced apoptosis and ER stress via GSK-3beta inhibition, independent of
      ATF4/CHOP pathway. Besides, GSK-3beta, rather than CHOP, may be a more promising
      therapeutic target for T2D.

PMID- 24884464
TI  - Detecting differentially methylated loci for multiple treatments based on high
      throughput methylation data.
AB  - BACKGROUND: Because of its important effects, as an epigenetic factor, on gene
      expression and disease development, DNA methylation has drawn much attention from
      researchers. Detecting differentially methylated loci is an important but
      challenging step in studying the regulatory roles of DNA methylation in a broad
      range of biological processes and diseases. Several statistical approaches have
      been proposed to detect significant methylated loci; however, most of them were
      designed specifically for case-control studies. RESULTS: Noticing that the age is
      associated with methylation level and the methylation data are not normally
      distributed, in this paper, we propose a nonparametric method to detect
      differentially methylated loci under multiple conditions with trend for Illumina
      Array Methylation data. The nonparametric method, Cuzick test is used to detect
      the differences among treatment groups with trend for each age group; then an
      overall p-value is calculated based on the method of combining those independent
      p-values each from one age group. CONCLUSIONS: We compare the new approach with
      other methods using simulated and real data. Our study shows that the proposed
      method outperforms other methods considered in this paper in term of power: it
      detected more biological meaningful differentially methylated loci than others.

PMID- 24884463
TI  - Sequence analysis on the information of folding initiation segments in ferredoxin
      like fold proteins.
AB  - BACKGROUND: While some studies have shown that the 3D protein structures are more
      conservative than their amino acid sequences, other experimental studies have
      shown that even if two proteins share the same topology, they may have different
      folding pathways. There are many studies investigating this issue with molecular
      dynamics or Go-like model simulations, however, one should be able to obtain the
      same information by analyzing the proteins' amino acid sequences, if the
      sequences contain all the information about the 3D structures. In this study, we
      use information about protein sequences to predict the location of their folding
      segments. We focus on proteins with a ferredoxin-like fold, which has a
      characteristic topology. Some of these proteins have different folding segments.
      RESULTS: Despite the simplicity of our methods, we are able to correctly
      determine the experimentally identified folding segments by predicting the
      location of the compact regions considered to play an important role in
      structural formation. We also apply our sequence analyses to some homologues of
      each protein and confirm that there are highly conserved folding segments despite
      the homologues' sequence diversity. These homologues have similar folding
      segments even though the homology of two proteins' sequences is not so high.
      CONCLUSION: Our analyses have proven useful for investigating the common or
      different folding features of the proteins studied.

PMID- 24884465
TI  - Cost analysis of periodontitis management in public sector specialist dental
      clinics.
AB  - BACKGROUND: The objective of this paper is to quantify the cost of periodontitis
      management at public sector specialist periodontal clinic settings and analyse
      the distribution of cost components. METHODS: Five specialist periodontal clinics
      in the Ministry of Health represented the public sector in providing clinical and
      cost data for this study. Newly-diagnosed periodontitis patients (N = 165) were
      recruited and followed up for one year of specialist periodontal care. Direct and
      indirect costs from the societal viewpoint were included in the cost analysis.
      They were measured in 2012 Ringgit Malaysia (MYR) and estimated from the societal
      perspective using activity-based and step-down costing methods, and substantiated
      by clinical pathways. Cost of dental equipment, consumables and labour (average
      treatment time) for each procedure was measured using activity-based costing
      method. Meanwhile, unit cost calculations for clinic administration, utilities
      and maintenance used step-down approach. Patient expenditures and absence from
      work were recorded via diary entries. The conversion from MYR to Euro was based
      on the 2012 rate (1? = MYR4). RESULTS: A total of 2900 procedures were provided,
      with an average cost of MYR 2820 (?705) per patient for the study year, and MYR
      376 (?94) per outpatient visit. Out of this, 90% was contributed by provider cost
      and 10% by patient cost; 94% for direct cost and 4% for lost productivity.
      Treatment of aggressive periodontitis was significantly higher than for chronic
      periodontitis (t-test, P = 0.003). Higher costs were expended as disease severity
      increased (ANOVA, P = 0.022) and for patients requiring surgeries (ANOVA, P <
      0.001). Providers generally spent most on consumables while patients spent most
      on transportation. CONCLUSIONS: Cost of providing dental treatment for
      periodontitis patients at public sector specialist settings were substantial and
      comparable with some non-communicable diseases. These findings provide basis for
      identifying potential cost-reducing strategies, estimating economic burden of
      periodontitis management and performing economic evaluation of the specialist
      periodontal programme.

PMID- 24884466
TI  - Psychometric properties of four fear of falling rating scales in people with
      Parkinson's disease.
AB  - BACKGROUND: Fear of falling (FOF) is commonly experienced in people with
      Parkinson's disease (PD). It is a predictor of recurrent falls, a barrier to
      physical exercise, and negatively associated with health-related quality of life.
      A variety of rating scales exist that assess different aspects of FOF but
      comprehensive head-to-head comparisons of their psychometric properties in people
      with PD are lacking. The aim of this study was to evaluate the psychometric
      properties of four FOF rating scales in people with PD. More specifically, we
      investigated and compared the scales' data completeness, scaling assumptions,
      targeting, and reliability. METHODS: The FOF rating scales were: the Falls
      Efficacy Scale-International (FES-I), the Swedish FES (FES(S)), the Activities
      specific Balance Confidence scale (ABC), and the modified Survey of Activities
      and Fear of Falling in the Elderly (mSAFFE). A postal survey was administered to
      174 persons with PD. Responders received a second survey after two weeks.
      RESULTS: The mean (SD) age and PD duration of the 102 responders were 73 (8) and
      7 (6) years, respectively. ABC had worse data completeness than the other scales
      (6.9 vs. 0.9-1.3% missing data). All scales had corrected item-total correlations
      exceeding 0.4 and showed acceptable reliabilities (Cronbach's alpha and
      Intraclass Correlation Coefficient (ICC) >0.80) but only FES-I had ICC >0.90. The
      standard error of measurements ranged from 7% (FES-I) to 12% (FES(S)), and the
      smallest detectable differences ranged from 20% (FES-I) to 33% (FES(S)) of the
      total score ranges. ABC and FES(S) had substantially more outliers than mSAFFE
      and FES-I (10 and 15 vs. 3 and 4, respectively) when the two test occasions were
      compared. CONCLUSIONS: When assessing FOF in people with PD, the findings in the
      present study favoured the choice of FES-I or mSAFFE. However, FES-I was the only
      scale with ICC >0.90 which has been suggested as a minimum when using a scale for
      individual comparisons.

PMID- 24884467
TI  - Distinguishing West Nile virus infection using a recombinant envelope protein
      with mutations in the conserved fusion-loop.
AB  - BACKGROUND: West Nile Virus (WNV) is an emerging mosquito-transmitted flavivirus
      that continues to spread and cause disease throughout several parts of the world,
      including Europe and the Americas. Specific diagnosis of WNV infections using
      current serological testing is complicated by the high degree of cross-reactivity
      between antibodies against other clinically relevant flaviviruses, including
      dengue, tick-borne encephalitis (TBEV), Japanese encephalitis (JEV), and yellow
      fever (YFV) viruses. Cross-reactivity is particularly problematic in areas where
      different flaviviruses co-circulate or in populations that have been immunized
      with vaccines against TBEV, JEV, or YFV. The majority of cross-reactive
      antibodies against the immunodominant flavivirus envelope (E) protein target a
      conserved epitope in the fusion loop at the distal end of domain II. METHODS: We
      tested a loss-of-function bacterially expressed recombinant WNV E protein
      containing mutations in the fusion loop and an adjacent loop domain as a possible
      diagnostic reagent. By comparing the binding of sera from humans infected with
      WNV or other flaviviruses to the wild type and the mutant E proteins, we analyzed
      the potential of this technology to specifically detect WNV antibodies. RESULTS:
      Using this system, we could reliably determine WNV infections. Antibodies from
      WNV-infected individuals bound equally well to the wild type and the mutant
      protein. In contrast, sera from persons infected with other flaviviruses showed
      significantly decreased binding to the mutant protein. By calculating the mean
      differences between antibody signals detected using the wild type and the mutant
      proteins, a value could be assigned for each of the flaviviruses, which
      distinguished their pattern of reactivity. CONCLUSIONS: Recombinant mutant E
      proteins can be used to discriminate infections with WNV from those with other
      flaviviruses. The data have important implications for the development of
      improved, specific serological assays for the detection of WNV antibodies in
      regions where other flaviviruses co-circulate or in populations that are
      immunized with other flavivirus vaccines.

PMID- 24884469
TI  - Memory-enhancing activities of the aqueous extract of Albizia adianthifolia
      leaves in the 6-hydroxydopamine-lesion rodent model of Parkinson's disease.
AB  - BACKGROUND: Albizia adianthifolia (Schumach.) W. Wright (Fabaceae) is a
      traditional herb largely used in the African traditional medicine as analgesic,
      purgative, anti-inflammatory, antioxidant, antimicrobial and memory-enhancer
      drug. This study was undertaken in order to evaluate the possible cognitive
      enhancing and antioxidative effects of the aqueous extract of A. adianthifolia
      leaves in the 6-hydroxydopamine-lesion rodent model of Parkinson's disease.
      METHODS: The effect of the aqueous extract of A. adianthifolia leaves (150 and
      300 mg/kg, orally, daily, for 21 days) on spatial memory performance was assessed
      using Y-maze and radial arm-maze tasks, as animal models of spatial memory.
      Pergolide-induced rotational behavior test was employed to validate unilateral
      damage to dopamine nigrostriatal neurons. Also, in vitro antioxidant activity was
      assessed through the estimation of total flavonoid and total phenolic contents
      along with determination of free radical scavenging activity. Statistical
      analyses were performed using two-way analysis of variance (ANOVA). Significant
      differences were determined by Tukey's post hoc test. F values for which p<0.05
      were regarded as statistically significant. Pearson's correlation coefficient and
      regression analysis were used in order to evaluate the association between
      behavioral parameters and net rotations in rotational behavior test. RESULTS: The
      6-OHDA-treated rats exhibited the following: decrease of spontaneous alternations
      percentage within Y-maze task and increase of working memory errors and reference
      memory errors within radial arm maze task. Administration of the aqueous extract
      of A. adianthifolia leaves significantly improved these parameters, suggesting
      positive effects on spatial memory formation. Also, the aqueous extract of A.
      adianthifolia leaves showed potent in vitro antioxidant activity. Furthermore, in
      vivo evaluation, the aqueous extract of A. adianthifolia leaves attenuated the
      contralateral rotational asymmetry observed by pergolide challenge in 6-OHDA
      treated rats. CONCLUSIONS: Taken together, our results suggest that the aqueous
      extract of A. adianthifolia leaves possesses antioxidant potential and might
      provide an opportunity for management neurological abnormalities in Parkinson's
      disease conditions.

PMID- 24884470
TI  - A model-based economic analysis of pre-pandemic influenza vaccination cost
      effectiveness.
AB  - BACKGROUND: A vaccine matched to a newly emerged pandemic influenza virus would
      require a production time of at least 6 months with current proven techniques,
      and so could only be used reactively after the peak of the pandemic. A pre
      pandemic vaccine, although probably having lower efficacy, could be produced and
      used pre-emptively. While several previous studies have investigated the cost
      effectiveness of pre-emptive vaccination strategies, they have not been directly
      compared to realistic reactive vaccination strategies. METHODS: An individual
      based simulation model of ~30,000 people was used to examine a pre-emptive
      vaccination strategy, assuming vaccination conducted prior to a pandemic using a
      low-efficacy vaccine. A reactive vaccination strategy, assuming a 6-month delay
      between pandemic emergence and availability of a high-efficacy vaccine, was also
      modelled. Social distancing and antiviral interventions were examined in
      combination with these alternative vaccination strategies. Moderate and severe
      pandemics were examined, based on estimates of transmissibility and clinical
      severity of the 1957 and 1918 pandemics respectively, and the cost effectiveness
      of each strategy was evaluated. RESULTS: Provided that a pre-pandemic vaccine
      achieved at least 30% efficacy, pre-emptive vaccination strategies were found to
      be more cost effective when compared to reactive vaccination strategies. Reactive
      vaccination coupled with sustained social distancing and antiviral interventions
      was found to be as effective at saving lives as pre-emptive vaccination coupled
      with limited duration social distancing and antiviral use, with both strategies
      saving approximately 420 life-years per 10,000 population for a moderate pandemic
      with a basic reproduction number of 1.9 and case fatality rate of 0.25%. Reactive
      vaccination was however more costly due to larger productivity losses incurred by
      sustained social distancing, costing $8 million per 10,000 population
      ($19,074/LYS) versus $6.8 million per 10,000 population ($15,897/LYS) for a pre
      emptive vaccination strategy. Similar trends were observed for severe pandemics.
      CONCLUSIONS: Compared to reactive vaccination, pre-emptive strategies would be
      more effective and more cost effective, conditional on the pre-pandemic vaccine
      being able to achieve a certain level of coverage and efficacy. Reactive
      vaccination strategies exist which are as effective at mortality reduction as pre
      emptive strategies, though they are less cost effective.

PMID- 24884472
TI  - Family needs in the chronic phase after severe brain injury in Denmark.
AB  - OBJECTIVE: This preliminary study aimed at investigating (1) changes in the
      status of family members between time of injury and follow-up in the chronic
      phase and (2) the most important needs within the family in the chronic phase and
      whether the needs were perceived as met. PARTICIPANTS: The sample comprised 42
      relatives (76% female, mean age = 53 years) of patients with severe brain injury,
      who had received intensive sub-acute rehabilitation. The relatives were contacted
      in the chronic phase after brain injury. OUTCOME MEASURE: A set of questions
      about demographics and time spent caregiving for the patient was completed. The
      relatives completed the revised version of the Family Needs Questionnaire, a
      questionnaire consisting of 37 items related to different needs following brain
      injury. RESULTS: Significant changes in status were found in employment (z = 
      3.464, p = 0.001) and co-habitation (z = -3.317, p = 0.001). The sub-scale
      'Health Information' (Mean = 3.50, SD = 0.73) had the highest mean importance
      rating, whereas the sub-scale 'Emotional support' (Mean = 3.07, SD = 0.79) had
      the lowest. When combining importance and met ratings, it was found that the five
      most important needs were only met in 41-50% of the total sample. CONCLUSION:
      Occupational and co-habitation status of the relatives was significantly affected
      by brain injury. A high number of relatives reported family needs not satisfied
      in the chronic phase. This requires an interventional approach for families to
      get these needs fulfilled individually, even after rehabilitation.

PMID- 24884471
TI  - Evolving epidemiology and antimicrobial resistance in spontaneous bacterial
      peritonitis: a two-year observational study.
AB  - BACKGROUND: Current recommendations for empirical antimicrobial therapy in
      spontaneous bacterial peritonitis (SBP) are based on quite old trials. Since
      microbial epidemiology and the management of patients have changed, whether these
      recommendations are still appropriate must be confirmed. METHODS: An
      observational study that exhaustively collected the clinical and biological data
      associated with positive ascitic fluid cultures was conducted in four French
      university hospitals in 2010-2011. RESULTS: Two hundred and sixty-eight
      documented positive cultures were observed in 190 cirrhotic patients (median age
      61.5 years, 58.5% Child score C). Of these, 57 were classified as confirmed SBP
      and 140 as confirmed bacterascites. The predominant flora was Gram-positive
      cocci, whatever the situation (SBP, bacterascites, nosocomial/health-care related
      or not). Enteroccocci (27.7% E. faecium) were isolated in 24% of the episodes,
      and in 48% from patients receiving quinolone prophylaxis. E. coli were
      susceptible to amoxicillin-clavulanate and to third-generation cephalosporins in
      62.5% and 89.5% of cases, respectively. No single antibiotic allowed
      antimicrobial coverage of more than 60%. Only combinations such as amoxicillin +
      third-generation cephalosporin or cotrimoxazole allowed coverage close to 75-80%
      in non-nosocomial episodes. Combinations based on broader spectrum antibiotics
      should be considered for empirical therapy of nosocomial infections. CONCLUSIONS:
      Our study confirmed the changing spectrum of pathogens in SBP and bacterascites,
      and the need for more complex antibiotic strategies than those previously
      recommended. Our findings also underline the need for new clinical trials
      conducted in the current epidemiological context.

PMID- 24884474
TI  - Care of the elderly: survey of teaching in an aging sub-Saharan Africa.
AB  - In sub-Saharan Africa (SSA), a rapidly aging population is presenting challenges
      to health care systems. Doctors need specialized knowledge to be prepared for the
      increase in age-related medical conditions. This study aims to investigate the
      current provision of geriatrics education (GE) in SSA medical schools and
      discover some of the barriers faced in its implementation. Questionnaires were
      sent to a list of medical schools in SSA, supplied by the sub-Saharan African
      Medical Schools Study. Responses were received from 25/135 institutions (19%),
      representing 11 countries in SSA. Of these institutions, 4% taught geriatrics and
      40% had no geriatrics teaching. The largest perceived barriers to GE were a lack
      of staff expertise (72%), lack of funding (52%), and absence of geriatrics in the
      national curricula (48%). There are still a large number of medical schools in
      SSA who do not teach geriatrics. Improvements in GE should be implemented through
      local approaches and national policy, while appreciating the cultural context and
      economic constraints of each country to prepare future doctors for the increasing
      challenges of an aging population. 

PMID- 24884473
TI  - Grape seed extract prevents skeletal muscle wasting in interleukin 10 knockout
      mice.
AB  - BACKGROUND: Muscle wasting is frequently a result of cancers, AIDS, chronic
      diseases and aging, which often links to muscle inflammation. Although grape seed
      extract (GSE) has been widely used as a human dietary supplement for health
      promotion and disease prevention primarily due to its anti-oxidative and anti
      inflammative effects, it is unknown whether GSE affects muscle wasting. The
      objective is to test the effects of GSE supplementation on inflammation and
      muscle wasting in interleukin (IL)-10 knockout mice, a recently developed model
      for human frailty. METHODS: Male IL-10 knockout (IL10KO) C57BL/6 mice at 6 weeks
      of age were assigned to either 0% or 0.1% GSE (in drinking water) groups (n=10)
      for 12 weeks, when skeletal muscle was sampled for analyses. Wild-type C57BL/6
      male mice were used as controls. RESULTS: Tibialis anterior muscle weight and
      fiber size of IL10KO mice were much lower than wild-type mice. IL10KO enhanced
      nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB)
      signaling and inflammasome formation when compared to wild-type mice.
      Phosphorylation of anabolic signaling was inhibited, whereas muscle specific
      ubiquitin ligase, AMP-activated protein kinase (AMPK) and apoptotic signaling
      were up-regulated in IL10KO mice. GSE supplementation effectively rectified these
      adverse changes in IL10KO muscle, which provide an explanation for the enhanced
      muscle mass, reduced protein degradation and apoptosis in GSE supplemented mice
      compared to IL10KO mice without supplementation. CONCLUSION: GSE supplementation
      effectively prevents muscle wasting in IL10KO mice, showing that GSE can be used
      as an auxiliary treatment for muscle loss associated with chronic inflammation
      and frailty.

PMID- 24884475
TI  - Can the type of gallstones be predicted with known possible risk factors?: A
      comparison between mixed cholesterol and black pigment stones.
AB  - BACKGROUND: Pathogenesis of gallstones (GS) is multifactorial and multiple
      genetic and environmental factors have been identified in different populations
      for different types of GS with varying prevalence. However the role of the each
      aetiological factor on the formation of mixed cholesterol and black pigment GS
      has not being addressed adequately. Hence in this study we attempted to compare
      known possible risk factors for mixed cholesterol and black pigment GS among two
      groups of patients with two types of GS. METHODS: The study was done on a cohort
      of patients with symptomatic GS admitted to the Teaching Hospital Peradeniya, Sri
      Lanka over a period of 18 months. Clinical and epidemiological data and physical
      parameters of the patients were recorded and surgically removed GS were analyzed
      chemically and physically to identify the type of GS. In addition lipid profile
      was done in all the patients with normal serum bilirubin levels. RESULTS: A total
      of 86 patients were included in the study. Mixed cholesterol GS was significantly
      common among females than males (chi2 test, p = 0.029). Mixed cholesterol GS was
      commonly seen among patients belonging to Moor ethnicity (chi2 test, p = 0.009).
      Majority of patients with mixed cholesterol GS had body mass index above 25 kg/m2
      (chi2 test, p = 0.018). Black pigment GS were significantly common among patients
      with type II diabetes mellitus (Fisher's exact test, p = 0.035). Further all the
      patients with chronic haemolytic anaemia and alcoholic cirrhosis had black
      pigment GS. Age, family history, Fasting Blood Glucose, dyslipidaemia, lipid
      profile, parity and use of oral contraceptive pills in females, smoking and
      alcohol intake in males did not differ significantly among patients in the two
      groups. CONCLUSION: Gender, ethnicity and body mass index can be used to predict
      the formation of mixed cholesterol GS and black pigment GS.

PMID- 24884476
TI  - Kinematics of pediatric crash dummies seated on vehicle seats with realistic belt
      geometry.
AB  - OBJECTIVE: A series of sled tests was performed using vehicle seats and Hybrid
      III 6-year-old (6YO) and 10YO anthropomorphic test devices (ATDs) to explore
      possibilities for improving occupant protection for children who are not using
      belt-positioning booster seats. METHODS: Cushion length was varied from
      production length of 450 mm to a shorter length of 350 mm. Lap belt geometry was
      set to rear, mid, and forward anchorage locations that span the range of lap belt
      angles found in vehicles. Six tests each were performed with the 6YO and 10YO
      Hybrid III ATDs. One additional test was performed using a booster seat with the
      6YO. The ATDs were positioned using an updated version of the University of
      Michigan Transportation Research Institute (UMTRI) seating procedure that
      positions the ATD hips further forward with longer seat cushions to reflect the
      effect of cushion length on posture that has been measured with child volunteers.
      ATD kinematics were evaluated using peak head excursion, peak knee excursion, the
      difference between peak head and peak knee excursion, and the maximum torso
      angle. RESULTS: Shortening the seat cushion improved kinematic outcomes,
      particularly for the 10YO. Lap belt geometry had a greater effect on kinematics
      with the longer cushion length, with mid or forward belt geometries producing
      better kinematics than the rearward belt geometry. The worst kinematics for both
      ATDs occurred with the long cushion length and rearward lap belt geometry. The
      improvements in kinematics from shorter cushion length or more forward belt
      geometry are smaller than those provided by a booster seat. CONCLUSIONS: The
      results show potential benefits in occupant protection from shortening cushion
      length and increasing lap belt angles, particularly for children the size of the
      10YO ATD.

PMID- 24884477
TI  - Case management training needs to support vocational rehabilitation for case
      managers and general practitioners: a survey study.
AB  - BACKGROUND: The use of the biopsychosocial model of health and case management
      for effective vocational rehabilitation (VR) has been confirmed for many health
      conditions. While Case and Condition Managers (CCMPs) use this approach in their
      everyday work, little is known about their views on training needs. A review of
      the training curriculum for General Practitioners' (GPs) revealed little training
      in VR and the biopsychosocial model of care. This study aims to identify Case and
      Condition Managers and GPs perceptions of their training needs in relation to
      employability and VR. METHODS: 80 Case and Condition Managers and 304 GPs working
      in NHS Lanarkshire, providing a comparison group, were invited to participate in
      this study. A self-completion questionnaire was developed and circulated for
      online completion with a second round of hardcopy questionnaires distributed.
      RESULTS: In total 45 responses were obtained from CCMPs, 5 from occupational
      health nurses (62% response rate) and 60 from GPs (20% response rate). CCMPs and
      the nursing group expressed a need for training but to a lesser extent than GP's.
      The GP responses demonstrated a need for high levels of training in
      case/condition management, the biopsychosocial model, legal and ethical issues
      associated with employment and VR, and management training. CONCLUSIONS: This
      survey confirms a need for further training of CCMPs and that respondent GPs in
      one health board are not fully equipped to deal with patients employability and
      vocational needs. GPs also reported a lack of understanding about the role of
      Case and Condition managers. Training for these professional groups and others
      involved in multidisciplinary VR could improve competencies and mutual
      understanding among those advising patients on return-to-work.

PMID- 24884478
TI  - Relationship between serum uric acid levels and hepatic steatosis in non-obese
      postmenopausal women.
AB  - OBJECTIVE: Serum uric acid levels have been reported to be associated with non
      alcoholic fatty liver disease (NAFLD). However, very few studies specifically
      examining the relationship between serum uric acid (SUA) levels and NAFLD in
      postmenopausal women have been reported in China, especially in postmenopausal
      women with normal body mass index (BMI) in whom NAFLD is not uncommon. METHODS: A
      cross-sectional study was employed of 528 Chinese normal-BMI postmenopausal women
      (aged 41-79 years) who participated in annual health check-ups. NAFLD is defined
      as a hepatic steatosis observed on liver ultrasonography in the absence of a
      second cause. Of all the participants, 121 women were diagnosed with hepatic
      steatosis (NAFLD group) and the others were without (non-NAFLD group). SUA
      quartiles were defined as follows: Q1, < 3.8 mg/dl; Q2, 3.8-4.4 mg/dl; Q3, 4.5
      5.0 mg/dl; Q4, 5.1-6.0 mg/dl. Stepwise multivariable regression analysis was used
      to assess the relationships between SUA level and other variables. The
      association between SUA quartiles and hepatic steatosis was assessed using binary
      logistic regression. RESULTS: Compared to the non-NAFLD group, the mean level of
      SUA was significantly higher in the NAFLD group (p < 0.01). The adjusted odds
      ratio (95% confidence interval) for the presence of hepatic steatosis in the
      highest SUA quartile vs. the lowest quartile was 2.774 (1.396-5.513) for all
      women (p < 0.01) after adjusting for the factors which were independently
      associated with uric acid level including waist circumference, high blood
      pressure, blood urea nitrogen, creatinine, gamma-glutamyltransferase, and
      triglycerides. Most estimates changed little after further adjustment for age,
      metabolic syndrome, drinking status, and smoking status. The presence of hepatic
      steatosis significantly increased in the third and fourth quartiles of SUA. The
      prevalence of hepatic steatosis increased gradually with an increasing SUA
      quartile (p for trend < 0.01). CONCLUSION: Higher SUA levels even within the
      normal range are positively and independently associated with the presence of
      hepatic steatosis in Chinese postmenopausal women with normal BMI.

PMID- 24884479
TI  - Hereditary breast and ovarian cancer: assessment of point mutations and copy
      number variations in Brazilian patients.
AB  - BACKGROUND: Germ line mutations in BRCA1 and BRCA2 (BRCA1/2) and other
      susceptibility genes have been identified as genetic causes of hereditary breast
      and ovarian cancer (HBOC). To identify the disease-causing mutations in a cohort
      of 120 Brazilian women fulfilling criteria for HBOC, we carried out a
      comprehensive screening of BRCA1/2, TP53 R337H, CHEK2 1100delC, followed by an
      analysis of copy number variations in 14 additional breast cancer susceptibility
      genes (PTEN, ATM, NBN, RAD50, RAD51, BRIP1, PALB2, MLH1, MSH2, MSH6, TP53,
      CDKN2A, CDH1 and CTNNB1). METHODS: Capillary sequencing and multiplex ligation
      dependent probe amplification (MLPA) were used for detecting point mutations and
      copy number variations (CNVs), respectively, for the BRCA1 and BRCA2 genes;
      capillary sequencing was used for point mutation for both variants TP53 R337H and
      CHEK2 1100delC, and finally array comparative genomic hybridization (array-CGH)
      was used for identifying CNVs in the 14 additional genes. RESULTS: The positive
      detection rate in our series was 26%. BRCA1 pathogenic mutations were found in 20
      cases, including two cases with CNVs, whereas BRCA2 mutations were found in 7
      cases. We also found three patients with the TP53 R337H mutation and one patient
      with the CHEK2 1100delC mutation. Seven (25%) pathogenic mutations in BRCA1/2
      were firstly described, including a splice-site BRCA1 mutation for which
      pathogenicity was confirmed by the presence of an aberrant transcript showing the
      loss of the last 62 bp of exon 7. Microdeletions of exon 4 in ATM and exon 2 in
      PTEN were identified in BRCA2-mutated and BRCA1/2-negative patients,
      respectively. CONCLUSIONS: In summary, our results showed a high frequency of
      BRCA1/2 mutations and a higher prevalence of BRCA1 (64.5%) gene. Moreover, the
      detection of the TP53 R337H variant in our series and the fact that this variant
      has a founder effect in our population prompted us to suggest that all female
      breast cancer patients with clinical criteria for HBOC and negative for BRCA1/2
      genes should be tested for the TP53 R337H variant. Furthermore, the presence of
      genomic structural rearrangement resulting in CNVs in other genes that predispose
      breast cancer in conjunction with BRCA2 point mutations demonstrated a highly
      complex genetic etiology in Brazilian breast cancer families.

PMID- 24884480
TI  - Assessment of fatigue in a large series of 1492 Brazilian patients with
      Spondyloarthritis.
AB  - BACKGROUND: The aim of the present study was to analyze the score of fatigue in a
      large cohort of Brazilian patients with SpA, comparing different disease patterns
      and its association with demographic and disease-specific variables. METHODS: A
      common protocol of investigation was prospectively applied to 1492 Brazilian
      patients classified as SpA according to the European Spondyloarthropathies Study
      Group (ESSG) criteria, attended at 29 reference centers. Clinical and demographic
      variables were recorded. Fatigue was evaluated using the first item of the Bath
      Ankylosing Spondylitis Disease Activity Index (BASDAI) questionnaire. RESULTS:
      The mean BASDAI fatigue score was 4.20 +/- 2.99. There was no significant
      difference in the fatigue score between the different SpA. Fatigue was higher in
      female patients (p < 0.001), with mixed (axial + peripheral) involvement (p <
      0.001) and in those who did not practice exercises (p < 0.001). Higher scores of
      fatigue were significantly associated with inflammatory low back pain (p =
      0.013), alternating buttock pain (p = 0.001), cervical pain (p = 0.001), and hip
      involvement (p = 0.005). Fatigue presented a moderate positive statistical
      correlation with Bath Ankylosing Spondylitis Functional Index (BASFI) (0.469; p <
      0.001) and Ankylosing Spondylitis Quality of Life (0.462; p < 0.001). CONCLUSION:
      In this large series of Brazilian SpA patients, higher fatigue scores were
      associated with female gender, sedentary, worse functionality, and quality of
      life.

PMID- 24884481
TI  - A condition closely mimicking IgG4-related disease despite the absence of serum
      IgG4 elevation and IgG4-positive plasma cell infiltration.
AB  - We describe a 74-year-old Japanese man with systemic fibroinflammatory conditions
      closely resembling those of immunoglobulin G4-related disease (IgG4-RD).
      Radiology and histology showed characteristics of IgG4-related tubulointerstitial
      nephritis, despite normal serum IgG4 value and scanty IgG4-positive plasma cell
      infiltration in each organ. This case suggests that a condition closely mimicking
      IgG4-RD may develop without IgG4-positive plasma cells and those exceptional
      cases should also be taken into account in the differential diagnosis of IgG4-RD.

PMID- 24884482
TI  - Comments on the paper showing an exceptionally favorable response to tofacitinib
      among Japanese rheumatoid patients and an issue surrounding clinical trial led by
      pharmaceutical company.

PMID- 24884484
TI  - Visible-light activation of the bimetallic chromophore-catalyst dyad: analysis of
      transient intermediates and reactivity toward organic sulfides.
AB  - In order to develop a new photocatalytic system, we designed a new redox-active
      module (5) to hold both a photosensitizer part, [Ru(II)(terpy)(bpy)X](n+) (where
      terpy = 2,2':6',2''-terpyridine and bpy = 2,2'-bipyridine), and a popular
      Jacobsen catalytic part, salen-Mn(III), covalently linked through a pyridine
      based electron-relay moiety. On the basis of nanosecond laser flash photolysis
      studies, an intramolecular electron transfer mechanism from salen-Mn(III) to
      photooxidized Ru(III) chromophore yielding the catalytically active high-valent
      salen-Mn(IV) species was proposed. To examine the reactivity of such
      photogenerated salen-Mn(IV), we employed organic sulfide as substrate. Detection
      of the formation of a Mn(III)-phenoxyl radical and a sulfur radical cation during
      the course of reaction using time-resolved transient absorption spectroscopy
      confirms the electron transfer nature of the reaction. This is the first report
      for the electron transfer reaction of organic sulfide with the photochemically
      generated salen-Mn(IV) catalytic center. 

PMID- 24884483
TI  - Impact of renal dysfunction on long-term outcomes of elderly patients with acute
      coronary syndrome: a longitudinal, prospective observational study.
AB  - BACKGROUND: This study investigated the impact of renal dysfunction (RD) on long
      term outcomes in elderly patients with acute coronary syndrome (ACS), and
      evaluated prognostic factors in elderly patients with ACS and RD. METHODS: This
      longitudinal prospective study included 184 consecutive patients who were
      admitted with ACS between January 2009 and January 2010 and also had RD. Patients
      were divided into five groups according to their estimated glomerular filtration
      rate (eGFR): 1) eGFR >= 90 mL/min/1.73 m2 with evidence of kidney damage, 2) 60
      <= eGFR <90 mL/min/1.73 m2, 3) 30 <= eGFR <60 mL/min/1.73 m2, 4) 15 <= eGFR <30
      mL/min/1.73 m2, and 5) eGFR <15 mL/min/1.73 m2. The primary endpoints were death
      and complications during hospitalization. The secondary endpoint was any major
      adverse cardiac event (MACE) during follow-up. RESULTS: The mean follow-up period
      was 502.2 +/- 203.6 days. The mean patient age was 73.7 +/- 9.4 years, and 61.4%
      of the patients were men. Severe RD (eGFR <30 mL/min/1.73 m2) was an independent
      predictor of MACE. Severe RD was associated with a low hemoglobin level, low left
      ventricular ejection fraction, and high levels of high-sensitivity C-reactive
      protein, N-terminal pro-B-type natriuretic peptide, and cystatin C. Survival was
      significantly poorer in patients with severe RD than in patients with mild RD.
      CONCLUSIONS: Among patients with ACS, severe RD was associated with advanced age,
      diabetes, hypertension, and cardiac dysfunction. Severe RD was an independent
      risk factor for MACE, and was associated with poor prognosis.

PMID- 24884485
TI  - Potential biomarkers relating pathological proteins, neuroinflammatory factors
      and free radicals in PD patients with cognitive impairment: a cross-sectional
      study.
AB  - BACKGROUND: Cognitive impairment strikingly reduces the quality of life of
      Parkinson's disease (PD) patients. Studies find that pathological proteins,
      neuroinflammatory factors and free radicals may involve in the pathogenesis of
      cognitive impairment of PD, however, results are inconclusive. METHODS: We
      recruited 62 PD patients and 31 healthy controls. PD patients were identified
      with cognitive impairment, including PD with mild cognitive impairment (PD-MCI)
      and PD with dementia (PDD) according to the diagnostic criteria for PD-MCI and
      PDD issued by Movement Disorder Society Task Force. The levels of pathological
      proteins, including beta-amyloid 1-42 (Abeta1-42),Total-tau (T-tau) and
      phosphorelated tau (P-tau), neuroinflammatory factors,including tumor necrosis
      factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), interleukin-6 (IL-6),
      interferon-gamma (INF-gamma) and prostaglandin E2 (PGE2), free radicals,
      including hydroxyl radical (.OH), hydrogen peroxide (H2O2) and nitric oxide (NO)
      in cerebrospinal fluid(CSF) were detected. The levels of above factors in CSF
      were compared among healthy controls and patients with and without cognitive
      impairment. Correlation analyses were performed between Montreal Cognitive
      Assessment (MoCA) score and the levels of above factors in CSF. RESULTS: T-tau
      level in CSF from PD-CI patients are significantly elevated comparing with those
      without cognitive impairment and controls (P = 0.016 and 0.004, respectively).
      The levels of P-tau (S396) and . OH in PD-CI patients are significantly higher
      than controls (P = 0.001 and 0.014, respectively). IL-6 levels in PD-CI patients
      are strikingly enhanced comparing with those without cognitive impairment (P =
      0.005). MoCA score is negatively correlated with the levels of T-tau (r = 
      0.340), P-tau (S396) (r = -0.448), IL-6 (r = -0.489) and . OH (r = -0.504) in PD
      CI patients. CONCLUSIONS: Elevated levels of T-tau, P-tau (S396), IL-6 and . OH
      in CSF are significantly correlated with cognitive impairment in PD patients.
      This investigation may suggest the potential biomarkers relating pathological
      proteins, neuroinflammatory factors and free radicals in PD patients with
      cognitive impairment.

PMID- 24884486
TI  - A multivariate approach to the integration of multi-omics datasets.
AB  - BACKGROUND: To leverage the potential of multi-omics studies, exploratory data
      analysis methods that provide systematic integration and comparison of multiple
      layers of omics information are required. We describe multiple co-inertia
      analysis (MCIA), an exploratory data analysis method that identifies co
      relationships between multiple high dimensional datasets. Based on a covariance
      optimization criterion, MCIA simultaneously projects several datasets into the
      same dimensional space, transforming diverse sets of features onto the same
      scale, to extract the most variant from each dataset and facilitate biological
      interpretation and pathway analysis. RESULTS: We demonstrate integration of
      multiple layers of information using MCIA, applied to two typical "omics"
      research scenarios. The integration of transcriptome and proteome profiles of
      cells in the NCI-60 cancer cell line panel revealed distinct, complementary
      features, which together increased the coverage and power of pathway analysis.
      Our analysis highlighted the importance of the leukemia extravasation signaling
      pathway in leukemia that was not highly ranked in the analysis of any individual
      dataset. Secondly, we compared transcriptome profiles of high grade serous
      ovarian tumors that were obtained, on two different microarray platforms and next
      generation RNA-sequencing, to identify the most informative platform and extract
      robust biomarkers of molecular subtypes. We discovered that the variance of RNA
      sequencing data processed using RPKM had greater variance than that with
      MapSplice and RSEM. We provided novel markers highly associated to tumor
      molecular subtype combined from four data platforms. MCIA is implemented and
      available in the R/Bioconductor "omicade4" package. CONCLUSION: We believe MCIA
      is an attractive method for data integration and visualization of several
      datasets of multi-omics features observed on the same set of individuals. The
      method is not dependent on feature annotation, and thus it can extract important
      features even when there are not present across all datasets. MCIA provides
      simple graphical representations for the identification of relationships between
      large datasets.

PMID- 24884487
TI  - Reconstructing the age and historical biogeography of the ancient flowering-plant
      family Hydatellaceae (Nymphaeales).
AB  - BACKGROUND: The aquatic flowering-plant family Hydatellaceae has a classic
      Gondwanan distribution, as it is found in Australia, India and New Zealand. To
      shed light on the biogeographic history of this apparently ancient branch of
      angiosperm phylogeny, we dated the family in the context of other seed-plant
      divergences, and evaluated its biogeography using parsimony and likelihood
      methods. We also explicitly tested the effect of different extinction rates on
      biogeographic inferences. RESULTS: We infer that the stem lineage of
      Hydatellaceae originated in the Lower Cretaceous; in contrast, its crown
      originated much more recently, in the early Miocene, with the bulk of its
      diversification after the onset of the Pliocene. Biogeographic reconstructions
      predict a mix of dispersal and vicariance events, but considerations of
      geological history preclude most vicariance events, besides a split at the root
      of the family between southern and northern clades. High extinction rates are
      plausible in the family, and when these are taken into account there is greater
      uncertainty in biogeographic inferences. CONCLUSIONS: A stem origin for
      Hydatellaceae in the Lower Cretaceous is consistent with the initial appearance
      of fossils attributed to its sister clade, the water lilies. In contrast, the
      crown clade is young, indicating that vicariant explanations for species outside
      Australia are improbable. Although long-distance dispersal is likely the primary
      driver of biogeographic distribution in Hydatellaceae, we infer that the recent
      drying out of central Australia divided the family into tropical vs.
      subtropical/temperate clades around the beginning of the Miocene.

PMID- 24884488
TI  - Is it possible to identify cases of coronary artery bypass graft postoperative
      surgical site infection accurately from claims data?
AB  - BACKGROUND: Claims data has usually been used in recent studies to identify cases
      of healthcare-associated infection. However, several studies have indicated that
      the ICD-9-CM codes might be inappropriate for identifying such cases from claims
      data; therefore, several researchers developed alternative identification models
      to correctly identify more cases from claims data. The purpose of this study was
      to investigate three common approaches to develop alternative models for the
      identification of cases of coronary artery bypass graft (CABG) surgical site
      infection, and to compare the performance between these models and the ICD-9-CM
      model. METHODS: The 2005-2008 National Health Insurance claims data and
      healthcare-associated infection surveillance data from two medical centers were
      used in this study for model development and model verification. In addition to
      the use of ICD-9-CM codes, this study also used classification algorithms, a
      multivariable regression model, and a decision tree model in the development of
      alternative identification models. In the classification algorithms, we defined
      three levels (strict, moderate, and loose) of the criteria in terms of their
      strictness. Sensitivity, specificity, positive predictive value, negative
      predictive value, and accuracy were used to evaluate the performance of each
      model. RESULTS: The ICD-9-CM-based model showed good specificity and negative
      predictive value, but sensitivity and positive predictive value were poor.
      Performances of the other models were varied, except for negative predictive
      value. Among the models, the performance of the decision tree model was
      excellent, especially in terms of positive predictive value. CONCLUSION: The
      accuracy of identification of cases of CABG surgical site infection is an
      important issue in claims data. Use of the decision tree model to identify such
      cases can improve the accuracy of patient-level outcome research. This model
      should be considered when performing future research using claims data.

PMID- 24884489
TI  - "Not too far to walk": the influence of distance on place of delivery in a
      western Kenya health demographic surveillance system.
AB  - BACKGROUND: Maternal health service coverage in Kenya remains low, especially in
      rural areas where 63% of women deliver at home, mainly because health facilities
      are too far away and/or they lack transport. The objectives of the present study
      were to (1) determine the association between the place of delivery and the
      distance of a household from the nearest health facility and (2) study the
      demographic characteristics of households with a delivery within a demographic
      surveillance system (DSS). METHODS: Census sampling was conducted for 13,333
      households in the Webuye health and demographic surveillance system area in 2008
      2009. Information was collected on deliveries that had occurred during the
      previous 12 months. Digital coordinates of households and sentinel locations such
      as health facilities were collected. Data were analyzed using STATA version 11.
      The Euclidean distance from households to health facilities was calculated using
      WinGRASS version 6.4. Hotspot analysis was conducted in ArcGIS to detect
      clustering of delivery facilities. Unadjusted and adjusted odds ratios were
      estimated using logistic regression models. P-values less than 0.05 were
      considered significant. RESULTS: Of the 13,333 households in the study area, 3255
      (24%) reported a birth, with 77% of deliveries being at home. The percentage of
      home deliveries increased from 30% to 80% of women living within 2 km from a
      health facility. Beyond 2 km, distance had no effect on place of delivery (OR
      1.29, CI 1.06-1.57, p = 0.011). Heads of households where women delivered at home
      were less likely to be employed (OR 0.598, CI 0.43-0.82, p = 0.002), and were
      less likely to have secondary education (OR 0.50, CI 0.41-0.61, p < 0.0001).
      Hotspot analysis showed households having facility deliveries were clustered
      around facilities offering comprehensive emergency obstetric care services.
      CONCLUSION: Households where the nearest facility was offering emergency
      obstetric care were more likely to have a facility delivery, but only if the
      facility was within 2 km of the home. Beyond the 2-km threshold, households were
      equally as likely to have home and facility deliveries. There is need for further
      research on other factors that affect the choice of place of delivery, and their
      relationships with maternal mortality.

PMID- 24884490
TI  - Comparative analysis of mitochondrial genomes between the hau cytoplasmic male
      sterility (CMS) line and its iso-nuclear maintainer line in Brassica juncea to
      reveal the origin of the CMS-associated gene orf288.
AB  - BACKGROUND: Cytoplasmic male sterility (CMS) is not only important for exploiting
      heterosis in crop plants, but also as a model for investigating nuclear
      cytoplasmic interaction. CMS may be caused by mutations, rearrangement or
      recombination in the mitochondrial genome. Understanding the mitochondrial genome
      is often the first and key step in unraveling the molecular and genetic basis of
      CMS in plants. Comparative analysis of the mitochondrial genome of the hau CMS
      line and its maintainer line in B. juneca (Brassica juncea) may help show the
      origin of the CMS-associated gene orf288. RESULTS: Through next-generation
      sequencing, the B. juncea hau CMS mitochondrial genome was assembled into a
      single, circular-mapping molecule that is 247,903 bp in size and 45.08% in GC
      content. In addition to the CMS associated gene orf288, the genome contains 35
      protein-encoding genes, 3 rRNAs, 25 tRNA genes and 29 ORFs of unknown function.
      The mitochondrial genome sizes of the maintainer line and another normal type
      line "J163-4" are both 219,863 bp and with GC content at 45.23%. The maintainer
      line has 36 genes with protein products, 3 rRNAs, 22 tRNA genes and 31
      unidentified ORFs. Comparative analysis the mitochondrial genomes of the hau CMS
      line and its maintainer line allowed us to develop specific markers to separate
      the two lines at the seedling stage. We also confirmed that different mitotypes
      coexist substoichiometrically in hau CMS lines and its maintainer lines in B.
      juncea. The number of repeats larger than 100 bp in the hau CMS line (16 repeats)
      are nearly twice of those found in the maintainer line (9 repeats). Phylogenetic
      analysis of the CMS-associated gene orf288 and four other homologous sequences in
      Brassicaceae show that orf288 was clearly different from orf263 in Brassica
      tournefortii despite of strong similarity. CONCLUSION: The hau CMS mitochondrial
      genome was highly rearranged when compared with its iso-nuclear maintainer line
      mitochondrial genome. This study may be useful for studying the mechanism of
      natural CMS in B. juncea, performing comparative analysis on sequenced
      mitochondrial genomes in Brassicas, and uncovering the origin of the hau CMS
      mitotype and structural and evolutionary differences between different mitotypes.

PMID- 24884491
TI  - Hospital-physician relations: the relative importance of economic, relational and
      professional attributes to organizational attractiveness.
AB  - BACKGROUND: Belgian hospitals face a growing shortage of physicians and
      increasingly competitive market conditions. In this challenging environment
      hospitals are struggling to build effective hospital-physician relationships
      which are considered to be a critical determinant of organizational success.
      METHODS: Employed physicians of a University hospital were surveyed.
      Organizational attributes were identified through the literature and two focus
      groups. Variables were measured using validated questionnaires. Descriptive
      analyses and linear regression were used to test the model and relative
      importance analyses were performed. RESULTS: The selected attributes predict
      hospital attractiveness significantly (79.3%). The relative importance analysis
      revealed that hospital attractiveness is most strongly predicted by professional
      attributes (35.3%) and relational attributes (29.7%). In particular, professional
      development opportunities (18.8%), hospital prestige (16.5%), organizational
      support (17.2%) and leader support (9.3%) were found to be most important.
      Besides these non-economic aspects, the employed physicians indicated pay and
      financial benefits (7.4%) as a significant predictor of hospital attractiveness.
      Work-life balance and job security were not significantly related to hospital
      attractiveness. CONCLUSIONS: This study shows that initiatives aimed at
      strengthening physicians' positive perceptions of professional and relational
      aspects of practicing medicine in hospitals, while assuring satisfactory
      financial conditions, may offer useful avenues for increasing the level of
      perceived hospital attractiveness. Overall, hospitals are advised to use a
      differentiated approach to increase their attractiveness to physicians.

PMID- 24884492
TI  - How populations differentiate despite gene flow: sexual and natural selection
      drive phenotypic divergence within a land fish, the Pacific leaping blenny.
AB  - BACKGROUND: Divergence between populations in reproductively important features
      is often vital for speciation. Many studies attempt to identify the cause of
      population differentiation in phenotype through the study of a specific selection
      pressure. Holistic studies that consider the interaction of several contrasting
      forms of selection are more rare. Most studies also fail to consider the history
      of connectivity among populations and the potential for genetic drift or gene
      flow to facilitate or limit phenotypic divergence. We examined the interacting
      effects of natural selection, sexual selection and the history of connectivity on
      phenotypic differentiation among five populations of the Pacific leaping blenny
      (Alticus arnoldorum), a land fish endemic to the island of Guam. RESULTS: We
      found key differences among populations in two male ornaments--the size of a
      prominent head crest and conspicuousness of a coloured dorsal fin--that reflected
      a trade-off between the intensity of sexual selection (male biased sex ratios)
      and natural selection (exposure to predators). This differentiation in
      ornamentation has occurred despite evidence suggesting extensive gene flow among
      populations, which implies that the change in ornament expression has been recent
      (and potentially plastic). CONCLUSIONS: Our study provides an early snapshot of
      divergence in reproductively important features that, regardless of whether it
      reflects genetic or plastic changes in phenotype, could ultimately form a
      reproductive barrier among populations.

PMID- 24884494
TI  - Meta-analysis of studies on biochemical marker tests for the diagnosis of
      premature rupture of membranes: comparison of performance indexes.
AB  - BACKGROUND: Premature rupture of the membranes (PROM) is most commonly diagnosed
      using physical examination; however, accurate decision making in ambiguous cases
      is a major challenge in current obstetric practice. As this may influence a
      woman's subsequent management, a number of tests designed to assist with
      confirming a diagnosis of PROM are commercially available. This study sought to
      evaluate the published data for the accuracy of two amniotic fluid-specific
      biomarker tests for PROM: insulin-like growth factor binding protein-1 (IGFBP-1 -
      Actim(r) PROM) and placental alpha microglobulin-1 (PAMG-1 - AmniSure(r)).
      METHODS: Main analysis included all PubMed referenced studies related to Actim(r)
      PROM and AmniSure(r) with available data to extract performance rates. To compare
      accuracy, a comparison of pooled indexes of both rapid tests was performed.
      Studies in which both tests were used in the same clinical population were also
      analysed. Membrane status, whether it was known or a suspected rupture, and
      inclusion or not of women with bleeding, were considered. RESULTS: All the
      available studies published in PubMed up to April 2013 were reviewed. Data were
      retrieved from 17 studies; 10 for Actim(r) PROM (n = 1066), four for AmniSure(r)
      (n = 1081) and three studies in which both biomarker tests were compared
      directly. The pooled analysis found that the specificity and positive predictive
      value were significantly higher for AmniSure(r) compared with Actim(r) PROM.
      However, when 762 and 1385 women with known or suspected rupture of membranes,
      respectively, were evaluated, AmniSure(r) only remained significantly superior in
      the latter group. Furthermore, when the two tests were compared directly in the
      same study no statistically significant differences were observed. Remarkably,
      women with a history or evidence of bleeding were excluded in all four studies
      for AmniSure(r), in two Actim(r) PROM studies and in two of the three studies
      reporting on both tests. CONCLUSIONS: No differences were observed in the
      performance of the two tests in studies where they were used under the same
      clinical conditions or in women with known membrane status. Although AmniSure(r)
      performed better in suspected cases of PROM, this may need further analysis as
      exclusion of bleeding may not be representative of the real clinical presentation
      of women with suspected PROM.

PMID- 24884495
TI  - Effects of metformin and exercise training, alone or in association, on cardio
      pulmonary performance and quality of life in insulin resistance patients.
AB  - BACKGROUND: Metformin (MET) therapy exerts positive effects improving glucose
      tolerance and preventing the evolution toward diabetes in insulin resistant
      patients. It has been shown that adding MET to exercise training does not improve
      insulin sensitivity. The aim of this study was to determine the effect of MET and
      exercise training alone or in combination on maximal aerobic capacity and, as a
      secondary end-point on quality of life indexes in individuals with insulin
      resistance. METHODS: 75 insulin resistant patients were enrolled and subsequently
      assigned to MET (M), MET with exercise training (MEx), and exercise training
      alone (Ex). 12-weeks of supervised exercise-training program was carried out in
      both Ex and MEx groups. Cardiopulmonary exercise test and SF-36 to evaluate
      Health-Related Quality of Life (HRQoL) was performed at basal and after 12-weeks
      of treatment. RESULTS: Cardiopulmonary exercise test showed a significant
      increase of peak VO2 in Ex and MEx whereas M showed no improvement of peak VO2 (?
      VO2 [CI 95%] Ex +0.26 [0.47 to 0.05] l/min; ? VO2 MEx +0.19 [0.33 to 0.05] l/min;
      ? VO2 M -0.09 [-0.03 to -0.15] l/min; M vs E p < 0.01; M vs MEx p < 0.01; MEx vs
      Ex p = ns). SF-36 highlighted a significant increase in general QoL index in the
      MEx (58.3 +/- 19 vs 77.3 +/- 16; p < 0.01) and Ex (62.1 +/- 17 vs 73.7 +/- 12; p
      < 0.005) groups. CONCLUSIONS: We evidenced that cardiopulmonary negative effects
      showed by MET therapy may be counterbalanced with the combination of exercise
      training. Given that exercise training associated with MET produced similar
      effects to exercise training alone in terms of maximal aerobic capacity and
      HRQoL, programmed exercise training remains the first choice therapy in insulin
      resistant patients.

PMID- 24884497
TI  - A randomised controlled trial on the Four Pillars Approach in managing pregnant
      women with anaemia in Yogyakarta-Indonesia: a study protocol.
AB  - BACKGROUND: Anaemia is a common health problem among pregnant women and a
      contributing factor with a major influence on maternal mortality in Indonesia.
      The Four Pillars Approach is a new approach to anaemia in pregnancy, combining
      four strategies to improve antenatal and delivery care. The primary objective of
      this study is to measure the effectiveness of the Four Pillars Approach. The
      barriers, the facilitators, and the patients' as well as the midwives'
      satisfaction with the Four Pillars Approach will also be measured.
      METHODS/DESIGN: This study will use a cluster randomised controlled trial. This
      intervention study will be conducted in the Public Health Centres with basic
      emergency obstetric care in Yogyakarta Special Province and in Central Java
      Province. We will involve all the Public Health Centres (24) with emergency
      obstetric care in Yogyakarta Special Province. Another 24 Public Health Centres
      with emergency obstetric care in Central Java Province which have similarities in
      their demographic, population characteristics, and facilities will also be
      involved. Each Public Health Centre will be asked to choose two or three nurse
      midwives to participate in this study. For the intervention group, the Public
      Health Centres in Yogyakarta Special Province, training on the Four Pillars
      Approach will be held prior to the model's implementation. Consecutively, we will
      recruit 360 pregnant women with anaemia to take part in part in the study to
      measure the effectiveness of the intervention. The outcome measurements are the
      differences in haemoglobin levels between the intervention and control groups in
      the third trimester of pregnancy, the frequency of antenatal care attendance, and
      the presence of a nurse-midwife during labour. Qualitative data will be used to
      investigate the barriers and facilitating factors, as to nurse-midwives'
      satisfaction with the implementation of the Four Pillars Approach. DISCUSSION: If
      the Four Pillars Approach is effective in improving the outcome for pregnant
      women with anaemia, this approach could be implemented nationwide and be taken
      into consideration to improve the outcome for other conditions in pregnancy,
      after further research. TRIAL REGISTRATION: Current Controlled Trials
      ISRCTN35822126.

PMID- 24884498
TI  - Brain cancer mortality in an agricultural and a metropolitan region of Rio de
      Janeiro, Brazil: a population-based, age-period-cohort study, 1996-2010.
AB  - BACKGROUND: Individuals who live in rural areas are at greater risk for brain
      cancer, and pesticide exposure may contribute to this increased risk. The aims of
      this research were to analyze the mortality trends and to estimate the age-period
      cohort effects on mortality rates from brain cancer in two regions in Rio de
      Janeiro, Brazil. METHODS: This descriptive study examined brain cancer mortality
      patterns in individuals of both sexes, >19 years of age, who died between 1996
      and 2010. They were residents of a rural (Serrana) or a non-rural (Metropolitan)
      area of Rio de Janeiro, Brazil. We estimated mortality trends using Joinpoint
      Regression analysis. Age-period-cohort models were estimated using Poisson
      regression analysis. RESULTS: The estimated annual percentage change in mortality
      caused by brain cancer was 3.8% in the Serrana Region (95% confidence interval
      (CI): 0.8-5.6) and -0.2% (95% CI: -1.2-0.7) in the Metropolitan Region. The
      results indicated that the relative risk was higher in the rural region for the
      more recent birth cohorts (1954 and later). Compared with the reference birth
      cohort (1945-49, Serrana Region), the relative risk was four times higher for
      individuals born between 1985 and 1989. CONCLUSIONS: The results of this study
      indicate that there is an increasing trend in brain cancer mortality rates in the
      rural Serrana Region in Brazil. A cohort effect occurred in the birth cohorts
      born in this rural area after 1954. At the ecological level, different
      environmental factors, especially the use of pesticides, may explain regional
      disparities in the mortality patterns from brain cancers.

PMID- 24884499
TI  - Highly efficient L-lactate production using engineered Escherichia coli with
      dissimilar temperature optima for L-lactate formation and cell growth.
AB  - L-Lactic acid, one of the most important chiral molecules and organic acids, is
      produced via pyruvate from carbohydrates in diverse microorganisms catalyzed by
      an NAD+-dependent L-lactate dehydrogenase. Naturally, Escherichia coli does not
      produce L-lactate in noticeable amounts, but can catabolize it via a
      dehydrogenation reaction mediated by an FMN-dependent L-lactate dehydrogenase. In
      aims to make the E. coli strain to produce L-lactate, three L-lactate
      dehydrogenase genes from different bacteria were cloned and expressed. The L
      lactate producing strains, 090B1 (B0013-070, DeltaldhA::diflldD::Pldh-ldhLca),
      090B2 (B0013-070, DeltaldhA::diflldD::Pldh-ldhStrb) and 090B3 (B0013-070,
      DeltaldhA::diflldD::Pldh-ldhBcoa) were developed from a previously developed D
      lactate over-producing strain, E. coli strain B0013-070 (ack
      ptappspflBdldpoxBadhEfrdA) by: (1) deleting ldhA to block D-lactate formation,
      (2) deleting lldD to block the conversion of L-lactate to pyruvate, and (3)
      expressing an L-lactate dehydrogenase (L-LDH) to convert pyruvate to L-lactate
      under the control of the ldhA promoter. Fermentation tests were carried out in a
      shaking flask and in a 25-l bioreactor. Strains 090B1, 090B2 or 090B3 were shown
      to metabolize glucose to L-lactate instead of D-lactate. However, L-lactate yield
      and cell growth rates were significantly different among the metabolically
      engineered strains which can be attributed to a variation between temperature
      optimum for cell growth and temperature optimum for enzymatic activity of
      individual L-LDH. In a temperature-shifting fermentation process (cells grown at
      37 degrees C and L-lactate formed at 42 degrees C), E. coli 090B3 was able to
      produce 142.2 g/l of L-lactate with no more than 1.2 g/l of by-products (mainly
      acetate, pyruvate and succinate) accumulated. In conclusion, the production of
      lactate by E. coli is limited by the competition relationship between cell growth
      and lactate synthesis. Enzymatic properties, especially the thermodynamics of an
      L-LDH can be effectively used as a factor to regulate a metabolic pathway and its
      metabolic flux for efficient L-lactate production. HIGHLIGHTS: The enzymatic
      thermodynamics was used as a tool for metabolic regulation. Minimizing the
      activity of L-lactate dehydrogenase in growth phase improved biomass
      accumulation. Maximizing the activity of L-lactate dehydrogenase improved lactate
      productivity in production phase.

PMID- 24884500
TI  - Screening for adulticidal activity against Anopheles arabiensis in ten plants
      used as mosquito repellent in South Africa.
AB  - BACKGROUND: Due to the development of resistance to synthetic insecticides,
      adverse effects to human health, non-target organisms and the environment, there
      is an urgent need to develop new insecticides, which are effective, safe,
      biodegrable and target-specific. This study was undertaken to evaluate the
      adulticidal activity of 10 plants used traditionally as mosquito repellents in
      South Africa. METHODS: The dried plant materials were extracted with
      dichloromethane (DCM) and ethanol (EtOH). The extracts were evaluated for
      adulticidal activity against Anopheles arabiensis mosquitoes, a potent malaria
      vector in South Africa. Adult mortality was observed after 24 hours of exposure.
      RESULTS: All the extracts showed adulticidal activity. The highest activity was
      observed in both DCM and EtOH extracts of Aloe ferox leaves with 98 and 86%
      mosquito mortality, respectively. The DCM extract of A. ferox leaves was then
      subjected to a dose-dependent bioassay to determine the EC50 value. The extract
      exhibited an EC50 value of 4.92 mg/ml. CONCLUSION: The results of the present
      study showed that the DCM extract of A. ferox leaves may have the potential to be
      used as an insecticide against An. arabiensis. Further studies to isolate and
      identify active compounds are in progress.

PMID- 24884502
TI  - Laboratory and field evaluation of the impact of washings on the effectiveness of
      LifeNet(r), Olyset(r) and PermaNet(r) 2.0 in two areas, where there is a high
      level of resistance of Anopheles gambiae to pyrethroids, Benin, West Africa.
AB  - BACKGROUND: An investigation carried out in Benin has shown that, in some areas
      close to rivers where density of mosquitoes is high, long-lasting, insecticidal
      bed nets (LLINs) are permanently used. In such areas, LLINs are washed every
      month. Based on this situation, the 20-wash minimum efficacy advised by the
      manufacturers would be inadequate. The main goal of this study was to evaluate
      the effectiveness of LifeNet(r), Olyset(r) and Permanet(r) 2.0 washed several
      times against Anopheles gambiae sensu stricto (s.s.) populations, which have
      developed high resistance to pyrethroids. METHODS: Efficacy of LifeNet(r),
      Olyset(r) and PermaNet(r) 2.0 washed 30 and 40 times was expressed in terms of
      blood-feeding inhibition rate, deterrence, induced exophily and mortality rates.
      This WHOPES phase II evaluation, conducted in experimental huts in Akron
      (southern Benin) and in Malanville (northern Benin), was accompanied by WHOPES
      Phase I evaluation. RESULTS: Over 40 successive washes, LifeNet(r) induced a
      mortality rate over 80% in phase I. However, beyond 10 washes, Permanet(r) 2.0
      and Olyset induced dramatically reduced mortality rates, respectively 12.5 and
      2.5%. With regard to Phase II results, unwashed LifeNet(r), LifeNet(r) and
      Olyset(r) washed 30 and 40 times induced a similar exophily rate per study site
      (at least 58% in Malanville and at least 71% in Akron). Regarding blood feeding
      inhibition, LifeNet(r) and Olyset(r) washed 30 and 40 times significantly reduced
      wild An. gambiae s.s. blood feeding showing a similar personal protection as
      unwashed LifeNet(r). LifeNet(r) washed 30 and 40 times induced mortality rates
      significantly higher than those induced by Olyset(r) and Permanet(r) 2.0 (P <
      0,05). CONCLUSION: LifeNet(r), followed by Olyset(r), have shown good efficacy
      against host-seeking resistant An. gambiae s.s. population in experimental huts
      in Benin. Lifenet(r) have shown to be an effective and promising vector control
      tool to prevent malaria in areas where repeated washings is a common practice in
      the community.

PMID- 24884501
TI  - FCGR2A and FCGR3A polymorphisms and clinical outcome in metastatic colorectal
      cancer patients treated with first-line 5-fluorouracil/folinic acid and
      oxaliplatin +/- cetuximab.
AB  - BACKGROUND: Polymorphisms of genes encoding the Fcy receptors (Fc fragment of IgG
      receptor 2A (FCGR2A) and 3A (FCGR3A)), which influence their affinity for the Fc
      fragment, have been linked to the pharmacodynamics of monoclonal antibodies. Most
      studies have been limited by small samples sizes and have reported inconsistent
      associations between the FCGR2A and the FCGR3A polymorphisms and clinical outcome
      in metastatic colorectal cancer (mCRC) patients treated with cetuximab. We
      investigated the association of these polymorphisms and clinical outcome in a
      large cohort of mCRC patients treated with first-line 5-fluorouracil/folinic acid
      and oxaliplatin (Nordic FLOX) +/- cetuximab in the NORDIC-VII study
      (NCT00145314). METHODS: 504 and 497 mCRC patients were evaluable for the FCGR2A
      and FCGR3A genotyping, respectively. Genotyping was performed on TaqMan ABI HT
      7900 (Applied Biosystems, Foster City, CA, USA) with pre-designed SNP genotyping
      assays for FCGR2A (rs1801274) and FCGR3A (rs396991). RESULTS: The response rate
      for patients with the FCGR2A R/R genotype was significantly increased when
      cetuximab was added to Nordic FLOX (31% versus 53%, interaction P = 0.03), but
      was not significantly different compared to the response rate of patients with
      the FCGR2A H/H or H/R genotypes given the same treatment. A larger increase in
      response rate with the addition of cetuximab to Nordic FLOX in patients with KRAS
      mutated tumors and the FCGR2A R/R genotype was observed (19% versus 50%,
      interaction P = 0.04). None of the FCGR3A polymorphisms were associated with
      altered response when cetuximab was added to Nordic FLOX (interaction P = 0.63).
      Neither of the FCGR polymorphisms showed any significant associations with
      progression-free survival or overall survival. CONCLUSION: Patients with KRAS
      mutated tumors and the FCGR2A R/R polymorphism responded poorly when treated with
      chemotherapy only, and experienced the most benefit of the addition of cetuximab
      in terms of response rate.

PMID- 24884493
TI  - Identification of the main venom protein components of Aphidius ervi, a
      parasitoid wasp of the aphid model Acyrthosiphon pisum.
AB  - BACKGROUND: Endoparasitoid wasps are important natural enemies of the widely
      distributed aphid pests and are mainly used as biological control agents.
      However, despite the increased interest on aphid interaction networks, only
      sparse information is available on the factors used by parasitoids to modulate
      the aphid physiology. Our aim was here to identify the major protein components
      of the venom injected at oviposition by Aphidius ervi to ensure successful
      development in its aphid host, Acyrthosiphon pisum. RESULTS: A combined large
      scale transcriptomic and proteomic approach allowed us to identify 16 putative
      venom proteins among which three gamma-glutamyl transpeptidases (gamma-GTs) were
      by far the most abundant. Two of the gamma-GTs most likely correspond to alleles
      of the same gene, with one of these alleles previously described as involved in
      host castration. The third gamma-GT was only distantly related to the others and
      may not be functional owing to the presence of mutations in the active site.
      Among the other abundant proteins in the venom, several were unique to A. ervi
      such as the molecular chaperone endoplasmin possibly involved in protecting
      proteins during their secretion and transport in the host. Abundant transcripts
      encoding three secreted cystein-rich toxin-like peptides whose function remains
      to be explored were also identified. CONCLUSIONS: Our data further support the
      role of gamma-GTs as key players in A. ervi success on aphid hosts. However, they
      also evidence that this wasp venom is a complex fluid that contains diverse, more
      or less specific, protein components. Their characterization will undoubtedly
      help deciphering parasitoid-aphid and parasitoid-aphid-symbiont interactions.
      Finally, this study also shed light on the quick evolution of venom components
      through processes such as duplication and convergent recruitment of virulence
      factors between unrelated organisms.

PMID- 24884504
TI  - TIMP-1 and responsiveness to gemcitabine in advanced breast cancer; results from
      a randomized phase III trial from the Danish breast cancer cooperative group.
AB  - BACKGROUND: Tissue inhibitor of metalloproteinases-1 (TIMP-1) has anti-apoptotic
      functions, which may protect TIMP-1 positive cancer cells from the effects of
      chemotherapy such as docetaxel and gemcitabine. The purpose of the present study
      was to evaluate TIMP-1 immunoreactivity as a prognostic and predictive marker in
      advanced breast cancer patients receiving docetaxel (D) or gemcitabine plus
      docetaxel (GD). METHODS: Patients with locally advanced or metastatic breast
      cancer who were assigned to D or GD by participation in a randomized phase III
      trial were included in the study. Assessment of TIMP-1 status was performed
      retrospectively on primary tumor whole-tissue sections by immunohistochemistry
      and tumor samples were considered positive if epithelial breast cancer cells were
      stained by the anti-TIMP-1 monoclonal antibody VT7. Time to progression (TTP) was
      the primary endpoint. Overall survival (OS) and response rate (RR) were secondary
      endpoints. Associations between TIMP-1 status and outcome after chemotherapy were
      analyzed by Kaplan-Meier estimates and Cox proportional hazards regression
      models. RESULTS: TIMP-1 status was available from 264 of 337 patients and 210
      (80%) of the tumors were classified as cancer cell TIMP-1 positive. No
      significant difference for TTP between TIMP-1 positive versus TIMP-1 negative
      patients was observed in multivariate analysis, and RR did not differ according
      to TIMP-1 status. However, patients with TIMP-1 positive tumors had a significant
      reduction in OS events (hazard ratio = 0.71, 95% confidence interval (CI) = 0.52
      0.98, P = 0.03). Additionally, a borderline significant interaction for OS was
      observed between TIMP-1 status and benefit from GD compared to D (Pinteraction =
      0.06) such that median OS increased by nine months for TIMP-1 negative patients
      receiving GD. CONCLUSIONS: TIMP-1 status was an independent prognostic factor for
      OS but not TTP in patients with advanced breast cancer receiving either D or GD.
      There was no statistically significant interaction between TIMP-1 status and
      treatment, but a trend towards an incremental OS from the addition of gemcitabine
      to docetaxel in patients with TIMP-1 negative tumors suggests further
      investigation.

PMID- 24884506
TI  - Acquired retinoschisis resolved after 23Gage pars plana vitrectomy in posterior
      microphthalmos.
AB  - BACKGROUND: Posterior microphthalmos combined with acquired retinoschisis is a
      rare entity. This report presents a case of acquired retinoschisis in a patient
      with posterior microphthalmos and discusses the management for such disease. The
      patient exhibited acquired peripheral retinal schisis in both eyes. CASE
      PRESENTATION: The patient presented with a fix scotoma and decrease in visual
      acuity for 2 weeks in his left eye. Ocular examination revealed that his best
      corrected visual acuity was 0.6 in right eye and 0.2 in left eye. The patient had
      amblyopia because of hyperopia with spherical equivalent of +11.75 diopters in
      the right eye and +12.00 diopters in the left eye. The axial lengths were 18.41
      mm in right and 18.43 mm in left eyes respectively. Slip lamp examination found
      normal anterior segments. Funduscopy showed bilateral retinoschisis in
      inferotemporal retina. The schisis in right eye was limited to peripheral retina
      whereas the schisis in left eye was bullous type. The schisis in the left eye
      extended from the periphery to the posterior macular region in left eye. A pars
      plana vitrectomy was performed in the left eye and visual acuity was restored to
      0.6. CONCLUSION: Posterior microphthalmos combined with retinoschisis is rare.
      When it appears in peripheral retina, the schisis remains stable. In cases where
      the schisis extends to posterior pole and affects the macula, surgery in the form
      of pars plana vitrectomy could be an option.

PMID- 24884505
TI  - Mitochondrial haplogroups modify the effect of black carbon on age-related
      cognitive impairment.
AB  - BACKGROUND: Traffic-related air pollution has been linked with impaired cognition
      in older adults, possibly due to effects of oxidative stress on the brain.
      Mitochondria are the main source of cellular oxidation. Haplogroups in
      mitochondrial DNA (mtDNA) mark individual differences in oxidative potential and
      are possible determinants of neurodegeneration. The aim of this study was to
      investigate whether mtDNA haplogroups determined differential susceptibility to
      cognitive effects of long-term exposure to black carbon (BC), a marker of traffic
      related air pollution. METHODS: We investigated 582 older men (72 +/- 7 years) in
      the VA Normative Aging Study cohort with <=4 visits per participant (1.8 in
      average) between 1995-2007. Low (<=25) Mini Mental State Examination (MMSE) was
      used to assess impaired cognition in multiple domains. We fitted repeated-measure
      logistic regression using validated-LUR BC estimated in the year before their
      first visit at the participant's address. RESULTS: Mitochondrial haplotyping
      identified nine haplogroups phylogenetically categorized in four clusters. BC
      showed larger effect on MMSE in Cluster 4 carriers, including I, W and X
      haplogroups, [OR = 2.7; 95% CI (1.3-5.6)], moderate effect in Cluster 1,
      including J and T haplogroups [OR = 1.6; 95% CI: (0.9-2.9)], and no effect in
      Cluster 2 (H and V haplogroups) [OR = 1.1; 95% CI: (0.8-1.5)] or Cluster 3 (K and
      U haplogroups) [OR = 1.0; 95% CI: (0.6-1.6)]. BC effect varied only moderately
      across the I, X, and W haplogroups or across the J and T haplogroups.
      CONCLUSIONS: The association of BC with impaired cognition was worsened in
      carriers of phylogenetically-related mtDNA haplogroups in Cluster 4. No BC
      effects were detected in Cluster 2 and 3 carriers. MtDNA haplotypes may modify
      individual susceptibility to the particle cognitive effects.

PMID- 24884503
TI  - Large-scale label-free comparative proteomics analysis of polo-like kinase 1
      inhibition via the small-molecule inhibitor BI 6727 (Volasertib) in BRAF(V600E)
      mutant melanoma cells.
AB  - Polo-like kinase 1 (Plk1) is a serine/threonine kinase that plays a key role
      during the cell cycle by regulating mitotic entry, progression, and exit. Plk1 is
      overexpressed in a variety of human cancers and is essential to sustained
      oncogenic proliferation, thus making Plk1 an attractive therapeutic target.
      However, the clinical efficacy of Plk1 inhibition has not emulated the
      preclinical success, stressing an urgent need for a better understanding of Plk1
      signaling. This study addresses that need by utilizing a quantitative proteomics
      strategy to compare the proteome of BRAF(V600E) mutant melanoma cells following
      treatment with the Plk1-specific inhibitor BI 6727. Employing label-free nano-LC
      MS/MS technology on a Q-exactive followed by SIEVE processing, we identified more
      than 20 proteins of interest, many of which have not been previously associated
      with Plk1 signaling. Here we report the down-regulation of multiple metabolic
      proteins with an associated decrease in cellular metabolism, as assessed by
      lactate and NAD levels. Furthermore, we have also identified the down-regulation
      of multiple proteasomal subunits, resulting in a significant decrease in 20S
      proteasome activity. Additionally, we have identified a novel association between
      Plk1 and p53 through heterogeneous ribonucleoprotein C1/C2 (hnRNPC), thus
      providing valuable insight into Plk1's role in cancer cell survival. 

PMID- 24884507
TI  - The study of anthropometric estimates in the visceral fat of healthy individuals.
AB  - BACKGROUND: Abdominal visceral fat affects the metabolic processes, and is an
      important risk factor for morbidity and mortality. The purpose of the study was
      to develop a quick and accurate estimate in the visceral fat area (VFA) of the L4
      L5 vertebrae using anthropometric predictor variables that can be measured
      conveniently. METHODS: A total of 227 individuals participated in this study and
      were further divided into a Modeling group (MG) and a Validation group (VG).
      Anthropometrics measurements (height, weight, waist circumference, hip
      circumference, age, and subcutaneous fat thickness) and VFACT were measured using
      computer assisted tomography for all participants. Multivariate linear regression
      analysis was applied to the MG to construct a VFA estimator using anthropometric
      predictor variables and to evaluate its performance using the VG. RESULTS: The
      estimate equation obtained from the MG were VFAANT = -144.66 + 1.84X1 + 1.35X2 +
      0.52X3 (r = 0.92, SEE =14.58 cm2, P < 0.001, n = 152). The X1, X2, and X3
      variables in the equation were denoted as waist circumference (WC), age, and
      abdomen subcutaneous fat thickness (AS). In addition, the correlation between
      VFAANT and VFACT showed a high correlation (r = 0.92). CONCLUSION: A rapid and
      accurate VFA estimation can be achieved by using only age, WC, and AS. The
      approach in the present study provides an easy and reliable estimate that can be
      applied widely in health and epidemiology studies.

PMID- 24884508
TI  - Comparison of cyclic fatigue resistance of original and counterfeit rotary
      instruments.
AB  - INTRODUCTION: In recent years, with the advances in counterfeiting methods,
      counterfeit products have reached the dental market. The purpose of this study
      was to compare the cyclic fatigue resistance of original and counterfeit rotary
      root canal instruments. MATERIALS AND METHODS: The cyclic fatigue of original and
      counterfeit ProTaper F2 endodontic instruments was tested (n = 20) in 3 mm radius
      steel canals with a 60 degrees  angle of curvature. The number of cycles to
      fracture (NCF) was calculated, and the data were subjected to the Student's t
      test (alpha = 0.05). RESULTS: The original instruments showed better cyclic
      fatigue resistance than the counterfeit ones (p < .001). The mean NCF was 483 +/-
      84 for the original files and 186 +/- 86 for the counterfeit files. CONCLUSIONS:
      The cyclic fatigue resistance of the counterfeit instruments was very low. As a
      result, clinicians should be careful not to purchase counterfeit products.

PMID- 24884509
TI  - Fbxw7 is an independent prognostic marker and induces apoptosis and growth arrest
      by regulating YAP abundance in hepatocellular carcinoma.
AB  - BACKGROUND: The E3 ubiquitin ligase Fbxw7 functions as a general tumor suppressor
      by targeting several well-known oncoproteins for ubiquitination and proteasomal
      degradation. However, the clinical significance of Fbxw7 and the mechanisms
      involved in the anti-cancer effect of Fbxw7 in HCC are not clear. METHOD: The
      Fbxw7 and YAP expression in 60 samples of surgical resected HCC and matched
      normal tumor-adjacent tissues were assessed using IHC or immunoblotting. Flow
      cytometry, caspase 3/7 activity assay, BrdU cell proliferation assay and MTT
      assay were used to detect proliferation and apoptosis of HCC cells. The
      regulatory effect of Fbxw7 on YAP in HCC cells was confirmed by qRT-PCR,
      immunoblotting and immunofluorescence. Co-immunoprecipitation was used to analyze
      interaction between YAP and Fbxw7. Nude mice subcutaneous injection, Ki-67
      staining and TUNEL assay were used to evaluate tumor growth and apoptosis in
      vivo. RESULTS: In this study, we found that Fbxw7 expression was impaired in HCC
      tissues and loss of Fbxw7 expression was correlated with poor clinicopathological
      features including large tumor size, venous infiltration, high pathological
      grading and advanced TNM stage. Additionally, we demonstrated that patients with
      positive Fbxw7 expression had a better 5-year survival and Fbxw7 was an
      independent factor for predicting the prognosis of HCC patients. We confirmed
      that Fbxw7 inhibited HCC by inducing both apoptosis and growth arrest. Elevated
      YAP expression was observed in the same cohort of HCC tissues. Pearson's
      correlation coefficient analysis indicated that Fbxw7 was inversely associated
      with YAP protein expression in HCC tissues. We also found that Fbxw7 regulated
      YAP protein abundance by targeting YAP for ubiquitination and proteasomal
      degradation in HCC. Furthermore, restoring YAP expression partially abrogated
      Fbxw7 induced HCC cell apoptosis and growth arrest in vitro and in vivo.
      CONCLUSION: These results indicate that Fbxw7 may serve as a prognostic marker
      and that YAP may be a potential target of Fbxw7 in HCC.

PMID- 24884511
TI  - Validation of the Spanish version of the Hip Outcome Score: a multicenter study.
AB  - BACKGROUND: The Hip Outcome Score (HOS) is a self-reported questionnaire
      evaluating the outcomes of treatment interventions for hip pathologies, divided
      in 19 items of activities of daily life (ADL) and 9 sports' items. The aim of the
      present study is to translate and validate HOS into Spanish. METHODS: A
      prospective and multicenter study with 100 patients undergoing hip arthroscopy
      was performed between June 2012 and January 2013. Crosscultural adaptation was
      used to translate HOS into Spanish. Patients completed the questionnaire before
      and after surgery. Feasibility, reliability, internal consistency, construct
      validity (correlation with Western Ontario and McMaster Universities
      Osteoarthritis Index), ceiling and floor effects and sensitivity to change were
      assessed for the present study. RESULTS: Mean age was 45.05 years old. 36 women
      and 64 men were included. Feasibility: 13% had at least one missing item within
      the ADL subscale and 17% within the sport subscale. Reliability: the translated
      version of HOS was highly reproducible with intraclass correlation coefficient of
      0.95 for ADL and 0.94 for the sports subscale. Internal consistency was confirmed
      with Cronbach's alpha >0.90 in both subscales. Construct validity showed
      statistically significant correlation with WOMAC. Ceiling effect was observed in
      6% and 12% for ADL and sports subscale, respectively. Floor effect was found in
      3% and 37% ADL and sports subscale, respectively. Large sensitivity to change was
      shown in both subscales. CONCLUSION: The translated version of HOS into Spanish
      has shown to be feasible, reliable and sensible to changes for patients
      undergoing hip arthroscopy. This validated translation of HOS allows for
      comparisons between studies involving either Spanish- or English-speaking
      patients. LEVEL OF EVIDENCE: Prognostic study, Level I.

PMID- 24884510
TI  - Construction and verification of the transcriptional regulatory response network
      of Streptococcus mutans upon treatment with the biofilm inhibitor carolacton.
AB  - BACKGROUND: Carolacton is a newly identified secondary metabolite causing altered
      cell morphology and death of Streptococcus mutans biofilm cells. To unravel key
      regulators mediating these effects, the transcriptional regulatory response
      network of S. mutans biofilms upon carolacton treatment was constructed and
      analyzed. A systems biological approach integrating time-resolved transcriptomic
      data, reverse engineering, transcription factor binding sites, and experimental
      validation was carried out. RESULTS: The co-expression response network
      constructed from transcriptomic data using the reverse engineering algorithm
      called the Trend Correlation method consisted of 8284 gene pairs. The regulatory
      response network inferred by superimposing transcription factor binding site
      information into the co-expression network comprised 329 putative transcriptional
      regulatory interactions and could be classified into 27 sub-networks each co
      regulated by a transcription factor. These sub-networks were significantly
      enriched with genes sharing common functions. The regulatory response network
      displayed global hierarchy and network motifs as observed in model organisms. The
      sub-networks modulated by the pyrimidine biosynthesis regulator PyrR, the
      glutamine synthetase repressor GlnR, the cysteine metabolism regulator CysR,
      global regulators CcpA and CodY and the two component system response regulators
      VicR and MbrC among others could putatively be related to the physiological
      effect of carolacton. The predicted interactions from the regulatory network
      between MbrC, known to be involved in cell envelope stress response, and the
      murMN-SMU_718c genes encoding peptidoglycan biosynthetic enzymes were
      experimentally confirmed using Electro Mobility Shift Assays. Furthermore, gene
      deletion mutants of five predicted key regulators from the response networks were
      constructed and their sensitivities towards carolacton were investigated.
      Deletion of cysR, the node having the highest connectivity among the regulators
      chosen from the regulatory network, resulted in a mutant which was insensitive to
      carolacton thus demonstrating not only the essentiality of cysR for the response
      of S. mutans biofilms to carolacton but also the relevance of the predicted
      network. CONCLUSION: The network approach used in this study revealed important
      regulators and interactions as part of the response mechanisms of S. mutans
      biofilm cells to carolacton. It also opens a door for further studies into novel
      drug targets against streptococci.

PMID- 24884513
TI  - The development and validation of oral cancer staging using administrative health
      data.
AB  - BACKGROUND: Oral cancer is a major global health problem. The complexity of
      histological prognosticators in oral cancer makes it difficult to compare the
      benefits of different treatment regimens. The Taiwanese National Health database
      provides an opportunity to assess correlations between outcome and treatment
      protocols and to compare the effects of different treatment regimens. However,
      the absence of indices of disease severity is a critical problem. The aim of this
      study was to ascertain how accurately we could assess the severity of oral cancer
      at the time of initial diagnosis on the basis of variables in a national
      database. METHODS: In the cancer registry database of a medical center in Taiwan,
      we identified 1067 histologically confirmed cases of oral cancer (ICD9 codes 140,
      141 and 143-145) that had been first diagnosed and subjected to initial treatment
      in this hospital. The clinical staging status was considered as the gold standard
      and we used concordance (C)-statistics to assess the model's predictive
      performance. We added the predictors of treatment modality, cancer subsite, and
      age group to our models. RESULTS: Our final overall model included treatment
      regimen, site, age, and two interaction terms; namely, interactions between
      treatment regimen and age and those between treatment regimen, site, and age. In
      this model, the C-statistics were 0.82-0.84 in male subjects and 0.96-0.99 in
      female subjects. Of the models stratified by age, the model that considered
      treatment regimen and site had the highest C-statistics for the interaction term,
      this value being greater than 0.80 in male subjects and 0.9 in female subjects.
      CONCLUSION: In this study, we found that adjusting for sex, age at first
      diagnosis, oral cancer subsite, and therapy regimen provided the best indicator
      of severity of oral cancer. Our findings provide a method for assessing cancer
      severity when information about staging is not available from a national health
      related database.

PMID- 24884512
TI  - Gene-diet interactions with polymorphisms of the MGLL gene on plasma low-density
      lipoprotein cholesterol and size following an omega-3 polyunsaturated fatty acid
      supplementation: a clinical trial.
AB  - BACKGROUND: Omega-3 (n-3) polyunsaturated fatty acid (PUFA) consumption increases
      low-density lipoprotein (LDL) cholesterol (C) concentrations and particle size.
      Studies showed that individuals with large, buoyant LDL particles have decreased
      risk of cardiovascular diseases. However, a large inter-individual variability is
      observed in LDL particle size. Genetic factors may explain the variability of LDL
      C concentrations and particle size after an n-3 PUFA supplementation. The
      monoglyceride lipase (MGLL) enzyme, encoded by the MGLL gene, plays an important
      role in lipid metabolism, especially lipoprotein metabolism. The aim of this
      study was to investigate if polymorphisms (SNPs) of the MGLL gene influence the
      variability of LDL-C and LDL particle size in response to an n-3 PUFA
      supplementation. METHODS: 210 subjects completed the study. They consumed 5 g/d
      of a fish oil supplement (1.9-2.2 g eicosapentaenoic acid and 1.1 g
      docosaexaenoic acid) during 6 weeks. Plasma lipids were measured before and after
      the supplementation period and 18 SNPs of the MGLL gene, covering 100% of common
      genetic variations (minor allele frequency >=0.05), have been genotyped using
      TaqMan technology (Life Technologies Inc., Burlington, ON, CA). RESULTS:
      Following the n-3 PUFA supplementation, 55% of subjects increased their LDL-C
      levels. In a model including the supplementation, genotype and
      supplementation*genotype effects, gene-diet interaction effects on LDL-C
      concentrations (rs782440, rs6776142, rs555183, rs6780384, rs6787155 and
      rs1466571) and LDL particle size (rs9877819 and rs13076593) were observed for the
      MGLL gene SNPs (p < 0.05). CONCLUSION: SNPs within the MGLL gene may modulate
      plasma LDL-C levels and particle size following an n-3 PUFA supplementation. This
      trial was registered at clinicaltrials.gov as NCT01343342.

PMID- 24884514
TI  - When to stop? Decision-making when children's cancer treatment is no longer
      curative: a mixed-method systematic review.
AB  - BACKGROUND: Children with cancer, parents, and clinicians, face difficult
      decisions when cure is no longer possible. Little is known about decision-making
      processes, how agreement is reached, or perspectives of different actors.
      Professionals voice concerns about managing parental expectations and beliefs,
      which can be contrary to their own and may change over time. We conducted the
      first systematic review to determine what constitutes best medico-legal practice
      for children under 19 years as context to exploring the perspectives of actors
      who make judgements and decisions when cancer treatment is no longer curative.
      METHODS: Theory-informed mixed-method thematic systematic review with theory
      development. RESULTS: Eight legal/ethical guidelines and 18 studies were
      included. Whilst there were no unresolved dilemmas, actors had different
      perspectives and motives. In line with guidelines, the best interests of the
      individual child informed decisions, although how different actors conceptualized
      'best interests' when treatment was no longer curative varied. Respect for
      autonomy was understood as following child/parent preferences, which varied from
      case to case. Doctors generally shared information so that parents alone could
      make an informed decision. When parents received reliable information, and
      personalized interest in their child, they were more likely to achieve shared
      trust and clearer transition to palliation. Although under-represented in
      research studies, young people's perspectives showed some differences to those of
      parents and professionals. For example, young people preferred to be informed
      even when prognosis was poor, and they had an altruistic desire to help others by
      participating in research. CONCLUSION: There needs to be fresh impetus to more
      effectively and universally implement the ethics of professionalism into daily
      clinical practice in order to reinforce humanitarian attitudes. Ethical
      guidelines and regulations attempt to bring professionals together by
      articulating shared values. While important, ethics training must be supported by
      institutions/organizations to assist doctors to maintain good professional
      standards. Findings will hopefully stimulate further normative and descriptive
      lines of research in this complex under-researched field. Future research needs
      to be undertaken through a more deliberative cultural lens that includes
      children's and multi-disciplinary team members' perspectives to more fully
      characterize and understand the dynamics of the decision-making process in this
      specific end-of life context.

PMID- 24884515
TI  - Food policies for physical and mental health.
AB  - Noncommunicable diseases (NCDs) account for the largest burden of early mortality
      and are predicted to cost the global community more than US $30 trillion over the
      next 20 years. Unhealthy dietary habits, in large part driven by substantial
      changes to global food systems, are recognised as major contributors to many of
      the common NCDs, including cardiovascular disease, cancer and diabetes. Recent
      evidence now indicates that unhealthy diets are also risk factors for mental
      disorders, particularly depression and dementia. This affords substantial scope
      to leverage on the established and developing approaches to the nutrition-related
      NCDs to address the large global burden of these mental disorders and reinforces
      the imperative for governments take substantial actions in regards to improving
      the food environment and consequent population health via policy initiatives. 

PMID- 24884516
TI  - Clinical implications of AGBL2 expression and its inhibitor latexin in breast
      cancer.
AB  - BACKGROUND: We investigated the expression status of AGBL2 and its inhibitor
      latexin in breast cancer stem cells and its clinical implications in order to lay
      a foundation for managing breast cancer. METHODS: CD44+/CD24- tumor cells (CSC)
      from clinical specimens were sorted using flow cytometry. AGBL2 expression status
      was detected in CSC and 126 breast cancer specimens by western blot and
      immunohistochemistry staining. The relationship between the AGBL2 protein and
      clinicopathological parameters and prognosis was subsequently determined. RESULT:
      As a result, CSC are more likely to generate new tumors in mice and cell
      microspheres that are deficient in non-obese diabetic/severe combined
      immunodeficiency mice (NOD/SCID) compared to the control group. The AGBL2 protein
      was expressed higher in CSC induced to epithelial to mesenchymal transition (EMT)
      when compared to the control cells, and was found to be related to CSC
      chemotherapy resistance. After Spearman regression correlation analysis, AGBL2
      was observed to be related to clinical stage, histological stage, and lymph node
      metastasis. In the Cox regression test, the AGBL2 protein was detected as an
      independent prognostic factor. Through immunoprecipitation, AGBL2 and latexin
      could form immune complexes. CONCLUSIONS: These results demonstrate that AGBL2 is
      a latexin-interacting protein that regulates the tubulin tyrosination cycle and
      is a potential target for intervention.

PMID- 24884517
TI  - Social class and gender patterning of insomnia symptoms and psychiatric distress:
      a 20-year prospective cohort study.
AB  - BACKGROUND: Psychiatric distress and insomnia symptoms exhibit similar patterning
      by gender and socioeconomic position. Prospective evidence indicates a bi
      directional relationship between psychiatric distress and insomnia symptoms so
      similarities in social patterning may not be coincidental. Treatment for insomnia
      can also improve distress outcomes. We investigate the extent to which the
      prospective patterning of distress over 20 years is associated with insomnia
      symptoms over that period. METHODS: 999 respondents to the Twenty-07 Study had
      been followed for 20 years from approximately ages 36-57 (73.2% of the living
      baseline sample). Psychiatric distress was measured using the GHQ-12 at baseline
      and at 20-year follow-up. Gender and social class were ascertained at baseline.
      Insomnia symptoms were self-reported approximately every five years. Latent class
      analysis was used to classify patterns of insomnia symptoms over the 20 years.
      Structural Equation Models were used to assess how much of the social patterning
      of distress was associated with insomnia symptoms. Missing data was addressed
      with a combination of multiple-imputation and weighting. RESULTS: Patterns of
      insomnia symptoms over 20 years were classified as either healthy, episodic,
      developing or chronic. Respondents from a manual social class were more likely to
      experience episodic, developing or chronic patterns than those from non-manual
      occupations but this was mostly explained by baseline psychiatric distress.
      People in manual occupations experiencing psychiatric distress however were
      particularly likely to experience chronic patterns of insomnia symptoms. Women
      were more likely to experience a developing pattern than men, independent of
      baseline distress. Psychiatric distress was more persistent over the 20 years for
      those in manual social classes and this effect disappeared when adjusting for
      insomnia symptoms. Irrespective of baseline symptoms, women, and especially those
      in a manual social class, were more likely than men to experience distress at age
      57. This overall association for gender, but not the interaction with social
      class, was explained after adjusting for insomnia symptoms. Sensitivity analyses
      supported these findings. CONCLUSIONS: Gender and socioeconomic inequalities in
      psychiatric distress are strongly associated with inequalities in insomnia
      symptoms. Treatment of insomnia or measures to promote healthier sleeping may
      therefore help alleviate inequalities in psychiatric distress.

PMID- 24884518
TI  - Complete sequencing of Novosphingobium sp. PP1Y reveals a biotechnologically
      meaningful metabolic pattern.
AB  - BACKGROUND: Novosphingobium sp. strain PP1Y is a marine alpha-proteobacterium
      adapted to grow at the water/fuel oil interface. It exploits the aromatic
      fraction of fuel oils as a carbon and energy source. PP1Y is able to grow on a
      wide range of mono-, poly- and heterocyclic aromatic hydrocarbons. Here, we
      report the complete functional annotation of the whole Novosphingobium genome.
      RESULTS: PP1Y genome analysis and its comparison with other Sphingomonadal
      genomes has yielded novel insights into the molecular basis of PP1Y's phenotypic
      traits, such as its peculiar ability to encapsulate and degrade the aromatic
      fraction of fuel oils. In particular, we have identified and dissected several
      highly specialized metabolic pathways involved in: (i) aromatic hydrocarbon
      degradation; (ii) resistance to toxic compounds; and (iii) the quorum sensing
      mechanism. CONCLUSIONS: In summary, the unraveling of the entire PP1Y genome
      sequence has provided important insight into PP1Y metabolism and, most
      importantly, has opened new perspectives about the possibility of its
      manipulation for bioremediation purposes.

PMID- 24884520
TI  - Analysis of the Pantoea ananatis pan-genome reveals factors underlying its
      ability to colonize and interact with plant, insect and vertebrate hosts.
AB  - BACKGROUND: Pantoea ananatis is found in a wide range of natural environments,
      including water, soil, as part of the epi- and endophytic flora of various plant
      hosts, and in the insect gut. Some strains have proven effective as biological
      control agents and plant-growth promoters, while other strains have been
      implicated in diseases of a broad range of plant hosts and humans. By analysing
      the pan-genome of eight sequenced P. ananatis strains isolated from different
      sources we identified factors potentially underlying its ability to colonize and
      interact with hosts in both the plant and animal Kingdoms. RESULTS: The pan
      genome of the eight compared P. ananatis strains consisted of a core genome
      comprised of 3,876 protein coding sequences (CDSs) and a sizeable accessory
      genome consisting of 1,690 CDSs. We estimate that ~106 unique CDSs would be added
      to the pan-genome with each additional P. ananatis genome sequenced in the
      future. The accessory fraction is derived mainly from integrated prophages and
      codes mostly for proteins of unknown function. Comparison of the translated CDSs
      on the P. ananatis pan-genome with the proteins encoded on all sequenced
      bacterial genomes currently available revealed that P. ananatis carries a number
      of CDSs with orthologs restricted to bacteria associated with distinct hosts,
      namely plant-, animal- and insect-associated bacteria. These CDSs encode proteins
      with putative roles in transport and metabolism of carbohydrate and amino acid
      substrates, adherence to host tissues, protection against plant and animal
      defense mechanisms and the biosynthesis of potential pathogenicity determinants
      including insecticidal peptides, phytotoxins and type VI secretion system
      effectors. CONCLUSIONS: P. ananatis has an 'open' pan-genome typical of bacterial
      species that colonize several different environments. The pan-genome incorporates
      a large number of genes encoding proteins that may enable P. ananatis to
      colonize, persist in and potentially cause disease symptoms in a wide range of
      plant and animal hosts.

PMID- 24884521
TI  - Increased expression of the pluripotency markers sex-determining region Y-box 2
      and Nanog homeobox in ovarian endometriosis.
AB  - BACKGROUND: The precise etiology of endometriosis is not fully understood; the
      involvement of stem cells theory is a new hypothesis. Related studies mainly
      focus on stemness-related genes, and pluripotency markers may play a role in the
      etiology of endometriosis. We aimed to analyze the transcription pluripotency
      factors sex-determining region Y-box 2 (SOX2), Nanog homeobox (NANOG), and
      octamer-binding protein 4 (OCT4) in the endometrium of reproductive-age women
      with and without ovarian endometriosis. METHODS: We recruited 26 women with
      laparoscopy-diagnosed ovarian endometriosis (endometriosis group) and 16 disease
      free women (control group) to the study. Endometrial and endometriotic samples
      were collected. SOX2, NANOG, and OCT4 expression were analyzed with quantitative
      real-time polymerase chain reaction, western blotting, and immunohistochemistry.
      RESULTS: Compared to the control group, SOX2 mRNA and protein expression was
      significantly higher in the eutopic endometrium of participants in the
      endometriosis group. In the endometriosis group, SOX2 and NANOG mRNA and protein
      expression were significantly increased in ectopic endometrium compared with
      eutopic endometrium; there was a trend towards lower OCT4 mRNA expression and
      higher OCT4 protein expression in ectopic endometrium. CONCLUSIONS: The
      transcription pluripotency factors SOX2 and NANOG were overexpression in ovarian
      endometriosis, their role in pathogenesis of endometriosis should be further
      studied.

PMID- 24884522
TI  - The effect of field strength on glioblastoma multiforme response in patients
      treated with the NovoTTFTM-100A system.
AB  - The NovoTTFTM-100A system is a portable device that delivers intermediate
      frequency alternating electric fields (TTFields, tumor treating fields) through
      transducer arrays arranged on the scalp. An ongoing trial is assessing its
      efficacy for newly diagnosed glioblastoma multiforme (GBM) and it has been FDA
      approved for recurrent GBM.The fields are believed to interfere with formation of
      the mitotic spindle as well as to affect polar molecules at telophase, thus
      preventing cell division. The position of the four arrays is unique to each
      patient and optimized based on the patient's imaging. We present three patients
      with GBM in whom the fields were adjusted at recurrence and the effects of each
      adjustment. We believe there may be a higher risk of treatment failure on the
      edges of the field where the field strength may be lower. The first patient
      underwent subtotal resection, radiotherapy with temozolomide (TMZ), and then
      began NovoTTF Therapy with metronomic TMZ. She had good control for nine months;
      however, new bifrontal lesions developed, and her fields were adjusted with a
      subsequent radiographic response. Over the next five months, her tumor burden
      increased and death was preceded by a right insular recurrence. A second patient
      underwent two resections followed by radiotherapy/TMZ and NovoTTF Therapy/TMZ.
      Six months later, two new distal lesions were noted, and he underwent further
      resection with adjustment of his fields. He remained stable over the subsequent
      year on NovoTTF Therapy and bevacizumab. A third patient on NovoTTF Therapy/TMZ
      remained stable for two years but developed a small, slow growing enhancing
      lesion, which was resected, and his fields were adjusted accordingly.
      Interestingly, the pathology showed giant cell GBM with multiple syncitial-type
      cells. Based on these observations, we believe that field strength may play a
      role in 'out of field' recurrences and that either the presence of a certain
      field strength may select for cells that are of a different size or that tumor
      cells may change size to avoid the effects of the TTFields.

PMID- 24884523
TI  - Yin Yang-1 suppresses invasion and metastasis of pancreatic ductal adenocarcinoma
      by downregulating MMP10 in a MUC4/ErbB2/p38/MEF2C-dependent mechanism.
AB  - BACKGROUND: Increasing evidence indicates an important role of transcription
      factor Yin Yang-1 (YY1) in human tumorigenesis. However, its function in cancer
      remains controversial and the relevance of YY1 to pancreatic ductal
      adenocarcinoma (PDAC) remains to be clarified. METHODS: In this study, we
      detected YY1 expression in clinical PDAC tissue samples and cell lines using
      quantitative RT-PCR, immunohistochemistry and western blotting. We also detected
      MUC4 and MMP10 mRNA levels in 108 PDAC samples using qRT-PCR and analyzed the
      correlations between YY1 and MUC4 or MMP10 expression. The role of YY1 in the
      proliferation, invasion and metastatic abilities of PDAC cells in vitro was
      studied by CCK-8 assay, cell migration and invasion assays. In vivo pancreatic
      tumor growth and metastasis was studied by a xenogenous subcutaneously implant
      model and a tail vein metastasis model. The potential mechanisms underlying YY1
      mediated tumor progression in PDAC were explored by digital gene expression (DGE)
      sequencing, signal transduction pathways blockage experiments and luciferase
      assays. Statistical analysis was performed using the SPSS 15.0 software. RESULTS:
      We found that the expression of YY1 in PDACs was higher compared with their
      adjacent non-tumorous tissues and normal pancreas tissues. However, PDAC patients
      with high level overexpression of YY1 had better outcome than those with low
      level overexpression. YY1 expression levels were statistically negatively
      correlated with MMP10 expression levels, but not correlated with MUC4 expression
      levels. YY1 overexpression suppressed, whereas YY1 knockdown enhanced, the
      proliferation, invasion and metastatic properties of BXPC-3 cells, both in vitro
      and in vivo. YY1 suppresses invasion and metastasis of pancreatic cancer cells by
      downregulating MMP10 in a MUC4/ErbB2/p38/MEF2C-dependent mechanism. CONCLUSIONS:
      The present study suggested that YY1 plays a negative role, i.e. is a tumor
      suppressor, in PDAC, and may become a valuable diagnostic and prognostic marker
      of PDAC.

PMID- 24884524
TI  - Processing faecal samples: a step forward for standards in microbial community
      analysis.
AB  - BACKGROUND: The microbial community analysis of stools requires optimised and
      standardised protocols for their collection, homogenisation, microbial disruption
      and nucleic acid extraction. Here we examined whether different layers of the
      stool are equally representative of the microbiome. We also studied the effect of
      stool water content, which typically increases in diarrhoeic samples, and of a
      microbial disruption method on DNA integrity and, therefore, on providing an
      unbiased microbial composition analysis. RESULTS: We collected faecal samples
      from healthy subjects and performed microbial composition analysis by
      pyrosequencing the V4 region of the 16S rRNA gene. To examine the effect of stool
      structure, we compared the inner and outer layers of the samples (N = 8). Both
      layers presented minor differences in microbial composition and abundance at the
      species level. These differences did not significantly bias the microbial
      community specific to an individual. To evaluate the effect of stool water
      content and bead-beating, we used various volumes of a water-based salt solution
      and beads of distinct weights before nucleic acid extraction (N = 4). The
      different proportions of water did not affect the UniFrac-based clustering of
      samples from the same subject However, the use or omission of a bead-beating step
      produced different proportions of Gram-positive and Gram-negative bacteria and
      significant changes in the UniFrac-based clustering of the samples. CONCLUSION:
      The degree of hydration and homogenisation of faecal samples do not significantly
      alter their microbial community composition. However, the use of bead-beating is
      critical for the proper detection of Gram-positive bacteria such as Blautia and
      Bifidobacterium.

PMID- 24884525
TI  - Development and validation of a tool to assess the physical and social
      environment associated with physical activity among adults in Sri Lanka.
AB  - BACKGROUND: Environmental characteristics are known to be associated with
      patterns of physical activity (PA). Although several validated tools exist, to
      measure the environment characteristics, these instruments are not necessarily
      suitable for application in all settings especially in a developing country. This
      study was carried out to develop and validate an instrument named the "Physical
      And Social Environment Scale--PASES" to assess the physical and social
      environmental factors associated with PA. This will enable identification of
      various physical and social environmental factors affecting PA in Sri Lanka,
      which will help in the development of more tailored intervention strategies for
      promoting higher PA levels in Sri Lanka. METHODS: The PASES was developed using a
      scientific approach of defining the construct, item generation, analysis of
      content of items and item reduction. Both qualitative and quantitative methods of
      key informant interviews, in-depth interviews and rating of the items generated
      by experts were conducted. A cross sectional survey among 180 adults was carried
      out to assess the factor structure through principal component analysis. Another
      cross sectional survey among a different group of 180 adults was carried out to
      assess the construct validity through confirmatory factor analysis. Reliability
      was assessed with test re-test reliability and internal consistency using
      Spearman r and Cronbach's alpha respectively. RESULTS: Thirty six items were
      selected after the expert ratings and were developed into interviewer
      administered questions. Exploration of factor structure of the 34 items which
      were factorable through principal component analysis with Quartimax rotation
      extracted 8 factors. The 34 item instrument was assessed for construct validity
      with confirmatory factor analysis which confirmed an 8 factor model (x2 = 339.9,
      GFI = 0.90). The identified factors were infrastructure for walking, aesthetics
      and facilities for cycling, vehicular traffic safety, access and connectivity,
      recreational facilities for PA, safety, social cohesion and social acceptance of
      PA with the two non-factorable factors, residential density and land use mix. The
      PASES also showed good test re-test reliability and a moderate level of internal
      consistency. CONCLUSIONS: The PASES is a valid and reliable tool which could be
      used to assess the physical and social environment associated with PA in Sri
      Lanka.

PMID- 24884526
TI  - Ferritin levels and risk of metabolic syndrome: meta-analysis of observational
      studies.
AB  - BACKGROUND: Elevated ferritin levels have been associated with single
      cardiovascular risk factors but the relationship to the presence of metabolic
      syndrome is inconclusive.The aim of this systematic review and meta-analysis of
      published observational studies was to estimate the association between serum
      ferritin levels and metabolic syndrome in adults. METHODS: The Pubmed, SCOPUS and
      the Cochrane Library databases were searched for epidemiological studies that
      assessed the association between ferritin levels and metabolic syndrome and were
      published before September 2013. There were no language restrictions. Two
      investigators independently selected eligible studies. Measures of association
      were pooled by using an inverse-variance weighted random-effects model. The
      heterogeneity among studies was examined using the I2 index. Publication bias was
      evaluated using the funnel plot. RESULTS: Twelve cross-sectional, one case
      control and two prospective studies met our inclusion criteria including data
      from a total of 56,053 participants. The pooled odds ratio (OR) for the metabolic
      syndrome comparing the highest and lowest category of ferritin levels was 1.73
      (95% CI: 1.54, 1.95; I2 = 75,4%). Subgroup analyses indicate that pooled OR was
      1.92 (95% CI: 1.61, 2.30; I2 = 78%) for studies adjusting for C-reactive protein
      (CRP), and 1.52 (95% CI:1. 36, 1.69; I2 = 41%) for studies that did not adjust
      for CRP (P = 0.044). This finding was remarkably robust in the sensitivity
      analysis. We did not find publication bias. CONCLUSIONS: The meta-analysis
      suggests that increased ferritin levels are independently and positively
      associated with the presence of the metabolic syndrome with an odds ratio higher
      than 1.73.

PMID- 24884527
TI  - ERP correlates of German Sign Language processing in deaf native signers.
AB  - BACKGROUND: The present study investigated the neural correlates of sign language
      processing of Deaf people who had learned German Sign Language (Deutsche
      Gebardensprache, DGS) from their Deaf parents as their first language. Correct
      and incorrect signed sentences were presented sign by sign on a computer screen.
      At the end of each sentence the participants had to judge whether or not the
      sentence was an appropriate DGS sentence. Two types of violations were
      introduced: (1) semantically incorrect sentences containing a selectional
      restriction violation (implausible object); (2) morphosyntactically incorrect
      sentences containing a verb that was incorrectly inflected (i.e., incorrect
      direction of movement). Event-related brain potentials (ERPs) were recorded from
      74 scalp electrodes. RESULTS: Semantic violations (implausible signs) elicited an
      N400 effect followed by a positivity. Sentences with a morphosyntactic violation
      (verb agreement violation) elicited a negativity followed by a broad centro
      parietal positivity. CONCLUSIONS: ERP correlates of semantic and morphosyntactic
      aspects of DGS clearly differed from each other and showed a number of
      similarities with those observed in other signed and oral languages. These data
      suggest a similar functional organization of signed and oral languages despite
      the visual-spacial modality of sign language.

PMID- 24884528
TI  - Arabidopsis AtHB7 and AtHB12 evolved divergently to fine tune processes
      associated with growth and responses to water stress.
AB  - BACKGROUND: Arabidopsis AtHB7 and AtHB12 transcription factors (TFs) belong to
      the homeodomain-leucine zipper subfamily I (HD-Zip I) and present 62% amino acid
      identity. These TFs have been associated with the control of plant development
      and abiotic stress responses; however, at present it is not completely understood
      how AtHB7 and AtHB12 regulate these processes. RESULTS: By using different
      expression analysis approaches, we found that AtHB12 is expressed at higher
      levels during early Arabidopsis thaliana development whereas AtHB7 during later
      developmental stages. Moreover, by analysing gene expression in single and double
      Arabidopsis mutants and in transgenic plants ectopically expressing these TFs, we
      discovered a complex mechanism dependent on the plant developmental stage and in
      which AtHB7 and AtHB12 affect the expression of each other. Phenotypic analysis
      of transgenic plants revealed that AtHB12 induces root elongation and leaf
      development in young plants under standard growth conditions, and seed production
      in water-stressed plants. In contrast, AtHB7 promotes leaf development,
      chlorophyll levels and photosynthesis and reduces stomatal conductance in mature
      plants. Moreover AtHB7 delays senescence processes in standard growth conditions.
      CONCLUSIONS: We demonstrate that AtHB7 and AtHB12 have overlapping yet specific
      roles in several processes related to development and water stress responses. The
      analysis of mutant and transgenic plants indicated that the expression of AtHB7
      and AtHB12 is regulated in a coordinated manner, depending on the plant
      developmental stage and the environmental conditions. The results suggested that
      AtHB7 and AtHB12 evolved divergently to fine tune processes associated with
      development and responses to mild water stress.

PMID- 24884529
TI  - Measuring the healthfulness of food retail stores: variations by store type and
      neighbourhood deprivation.
AB  - BACKGROUND: The consumer nutrition environment has been conceptualised as in
      store environmental factors that influence food shopping habits. More healthful
      in-store environments could be characterised as those which promote healthful
      food choices such as selling good quality healthy foods or placing them in
      prominent locations to prompt purchasing. Research measuring the full-range of in
      store environmental factors concurrently is limited. PURPOSE: To develop a
      summary score of 'healthfulness' composed of nine in-store factors that influence
      food shopping behaviour, and to assess this score by store type and neighbourhood
      deprivation. METHODS: A cross-sectional survey of 601 retail food stores,
      including supermarkets, grocery stores and convenience stores, was completed in
      Hampshire, United Kingdom between July 2010 and June 2011. The survey measured
      nine variables (variety, price, quality, promotions, shelf placement, store
      placement, nutrition information, healthier alternatives and single fruit sale)
      to assess the healthfulness of retail food stores on seven healthy and five less
      healthy foods that are markers of diet quality. Four steps were completed to
      create nine individual variable scores and another three to create an overall
      score of healthfulness for each store. RESULTS: Analysis of variance showed
      strong evidence of a difference in overall healthfulness by store type (p <
      0.001). Large and premium supermarkets offered the most healthful shopping
      environments for consumers. Discount supermarkets, 'world', convenience and
      petrol stores offered less healthful environments to consumers however there was
      variation across the healthfulness spectrum. No relationship between overall
      healthfulness and neighbourhood deprivation was observed (p = 0.1). CONCLUSIONS:
      A new composite measure of nine variables that can influence food choices was
      developed to provide an overall assessment of the healthfulness of retail food
      stores. This composite score could be useful in future research to measure the
      relationship between main food store and quality of diet, and to evaluate the
      effects of multi-component food environment interventions.

PMID- 24884530
TI  - How can knowledge exchange portals assist in knowledge management for evidence
      informed decision making in public health?
AB  - BACKGROUND: Knowledge exchange portals are emerging as web tools that can help
      facilitate knowledge management in public health. We conducted a review to better
      understand the nature of these portals and their contribution to knowledge
      management in public health, with the aim of informing future development of
      portals in this field. METHODS: A systematic literature search was conducted of
      the peer-reviewed and grey literature to identify articles that described the
      design, development or evaluation of Knowledge Exchange Portals KEPs in the
      public health field. The content of the articles was analysed, interpreted and
      synthesised in light of the objectives of the review. RESULTS: The systematic
      search yielded 2223 articles, of which fifteen were deemed eligible for review,
      including eight case studies, six evaluation studies and one commentary article.
      Knowledge exchange portals mainly included design features to support knowledge
      access and creation, but formative evaluation studies examining user needs
      suggested collaborative features supporting knowledge exchange would also be
      useful. Overall web usage statistics revealed increasing use of some of these
      portals over time; however difficulties remain in retaining users. There is some
      evidence to suggest that the use of a knowledge exchange portal in combination
      with tailored and targeted messaging can increase the use of evidence in policy
      and program decision making at the organisational level. CONCLUSIONS: Knowledge
      exchange portals can be a platform for providing integrated access to relevant
      content and resources in one location, for sharing and distributing information
      and for bringing people together for knowledge exchange. However more performance
      evaluation studies are needed to determine how they can best support evidence
      informed decision making in public health.

PMID- 24884531
TI  - Natural rice rhizospheric microbes suppress rice blast infections.
AB  - BACKGROUND: The natural interactions between plant roots and their rhizospheric
      microbiome are vital to plant fitness, modulating both growth promotion and
      disease suppression. In rice (Oryza sativa), a globally important food crop, as
      much as 30% of yields are lost due to blast disease caused by fungal pathogen
      Magnaporthe oryzae. Capitalizing on the abilities of naturally occurring rice
      soil bacteria to reduce M. oryzae infections could provide a sustainable solution
      to reduce the amount of crops lost to blast disease. RESULTS: Naturally occurring
      root-associated rhizospheric bacteria were isolated from California field grown
      rice plants (M-104), eleven of which were taxonomically identified by 16S rRNA
      gene sequencing and fatty acid methyl ester (FAME) analysis. Bacterial isolates
      were tested for biocontrol activity against the devastating foliar rice fungal
      pathogen, M. oryzae pathovar 70-15. In vitro, a Pseudomonas isolate, EA105,
      displayed antibiosis through reducing appressoria formation by nearly 90% as well
      as directly inhibiting fungal growth by 76%. Although hydrogen cyanide (HCN) is a
      volatile commonly produced by biocontrol pseudomonads, the activity of EA105
      seems to be independent of its HCN production. During in planta experiments,
      EA105 reduced the number of blast lesions formed by 33% and Pantoea agglomerans
      isolate, EA106 by 46%. Our data also show both EA105 and EA106 trigger jasmonic
      acid (JA) and ethylene (ET) dependent induced systemic resistance (ISR) response
      in rice. CONCLUSIONS: Out of 11 bacteria isolated from rice soil, pseudomonad
      EA105 most effectively inhibited the growth and appressoria formation of M.
      oryzae through a mechanism that is independent of cyanide production. In addition
      to direct antagonism, EA105 also appears to trigger ISR in rice plants through a
      mechanism that is dependent on JA and ET signaling, ultimately resulting in fewer
      blast lesions. The application of native bacteria as biocontrol agents in
      combination with current disease protection strategies could aid in global food
      security.

PMID- 24884532
TI  - Intravenous ascorbic acid as an adjuvant to interleukin-2 immunotherapy.
AB  - Interleukin-2 (IL-2) therapy has been demonstrated to induce responses in 10-20%
      of advanced melanoma and renal cell carcinoma patients, which translates into
      durable remissions in up to half of the responsers. Unfortunately the use of IL-2
      has been associated with severe toxicity and death. It has been previously
      observed and reported that IL-2 therapy causes a major drop in circulating levels
      of ascorbic acid (AA). The IL-2 induced toxicity shares many features with sepsis
      such as capillary leakage, systemic complement activation, and a relatively non
      specific rise in inflammatory mediators such as TNF-alpha, C-reactive protein,
      and in advanced cases organ failure. Animal models and clinical studies have
      shown rapid depletion of AA in conditions of sepsis and amelioration associated
      with administration of AA (JTM 9:1-7, 2011). In contrast to other approaches to
      dealing with IL-2 toxicity, which may also interfere with therapeutic effects, AA
      possesses the added advantage of having direct antitumor activity through
      cytotoxic mechanisms and suppression of angiogenesis. Here we present a
      scientific rationale to support the assessment of intravenous AA as an adjuvant
      to decrease IL-2 mediated toxicity and possibly increase treatment efficacy. 

PMID- 24884533
TI  - Zwitterionic poly(amino acid methacrylate) brushes.
AB  - A new cysteine-based methacrylic monomer (CysMA) was conveniently synthesized via
      selective thia-Michael addition of a commercially available methacrylate-acrylate
      precursor in aqueous solution without recourse to protecting group chemistry.
      Poly(cysteine methacrylate) (PCysMA) brushes were grown from the surface of
      silicon wafers by atom-transfer radical polymerization. Brush thicknesses of ca.
      27 nm were achieved within 270 min at 20  degrees C. Each CysMA residue comprises
      a primary amine and a carboxylic acid. Surface zeta potential and atomic force
      microscopy (AFM) studies of the pH-responsive PCysMA brushes confirm that they
      are highly extended either below pH 2 or above pH 9.5, since they possess either
      cationic or anionic character, respectively. At intermediate pH, PCysMA brushes
      are zwitterionic. At physiological pH, they exhibit excellent resistance to
      biofouling and negligible cytotoxicity. PCysMA brushes undergo photodegradation:
      AFM topographical imaging indicates significant mass loss from the brush layer,
      while XPS studies confirm that exposure to UV radiation produces surface aldehyde
      sites that can be subsequently derivatized with amines. UV exposure using a
      photomask yielded sharp, well-defined micropatterned PCysMA brushes
      functionalized with aldehyde groups that enable conjugation to green fluorescent
      protein (GFP). Nanopatterned PCysMA brushes were obtained using interference
      lithography, and confocal microscopy again confirmed the selective conjugation of
      GFP. Finally, PCysMA undergoes complex base-catalyzed degradation in alkaline
      solution, leading to the elimination of several small molecules. However, good
      long-term chemical stability was observed when PCysMA brushes were immersed in
      aqueous solution at physiological pH. 

PMID- 24884534
TI  - Spatial distribution, work patterns, and perception towards malaria interventions
      among temporary mobile/migrant workers in artemisinin resistance containment
      zone.
AB  - BACKGROUND: Mobile populations are at a high risk of malaria infection and
      suspected to carry and spread resistant parasites. The Myanmar National Malaria
      Control Programme focuses on preventive interventions and vector control measures
      for the temporary mobile/migrant workers in Myanmar Artemisinin Resistance
      Containment Zones. METHODS: A prospective cross-sectional study was conducted in
      2012 in Kawthaung and Bokepyin townships of Tanintharyi Region, Myanmar, covering
      192 mobile/migrant aggregates. The objectives were to identify the spatial
      distribution of the mobile/migrant populations, and to assess knowledge,
      attitudes, perceptions, and practices concerning malaria prevention and control,
      and their preferred methods of interventions. The structure of the 192 migrant
      aggregates was investigated using a migrant mapping tool. Individual and
      household information was collected by structured interviews of 408 respondents
      from 39 aggregates, supplemented by 12 in-depth interviews of health care
      providers, authorities, volunteers, and employers. Data were analyzed by
      triangulating quantitative and qualitative data. RESULTS: The primary reasons for
      the limitation in access to formal health services for suspected malaria within
      24 hours were identified to be scattered distribution of migrant aggregates,
      variable working hours and the lack of transportation. Only 19.6% of respondents
      reported working at night from dusk to dawn. Among study populations, 73%
      reported a perceived risk of contracting malaria and 60% reported to know how to
      confirm a suspected case of malaria. Moreover, only 15% was able to cite correct
      antimalarial drugs, and less than 10% believed that non-compliance with
      antimalarial treatment may be related to the risk of drug resistance. About 50%
      of study population reported to seeking health care from the public sector, and
      to sleep under ITNs/LLINs the night before the survey. There was a gap in
      willingness to buy ITNs/LLINs and affordability (88.5% vs. 60.2%) which may
      affect their sustained and consistent use. Only 32.4% across all aggregates
      realized the importance of community participation in effective malaria
      prevention and control. CONCLUSIONS: Community-based innovative approaches
      through strong collaboration and coordination of multi-stakeholders are desirable
      for relaying information on ITNs/LLINs, rapid diagnostic test, and artemisinin
      combination therapy and drug resistance successfully across the social and
      economic diversity of mobile/migrant aggregates in Myanmar.

PMID- 24884535
TI  - Detection of activated KRAS from cancer patient peripheral blood using a weighted
      enzymatic chip array.
AB  - BACKGROUND: The KRAS oncogene was one of the earliest discoveries of genetic
      alterations in colorectal and lung cancers. Moreover, KRAS somatic mutations
      might be used for predicting the efficiency of anti-EGFR therapeutic drugs. The
      purpose of this research was to improve Activating KRAS Detection Chip by using a
      weighted enzymatic chip array (WEnCA) platform to detect activated KRAS mutations
      status in the peripheral blood of non-small-cell lung cancer (NSCLC) and
      colorectal cancer (CRC) patients in Taiwan. METHODS: Our laboratory developed an
      Activating KRAS Detection Chip and a WEnCA technique that can detect activated
      KRAS mutation status by screening circulating cancer cells in the surrounding
      bloodstream. We collected 390 peripheral blood samples of NSCLC patients (n =
      210) and CRC patients (n = 180) to evaluate clinical KRAS activation using this
      gene array diagnosis apparatus, an Activating KRAS Detection Chip and a WEnCA
      technique. Subsequently, we prospectively enrolled 88 stage III CRC patients who
      received adjuvant FOLFOX-4 chemotherapy with or without cetuximab. We compared
      the chip results of preoperative blood specimens and their relationship with
      disease control status in these patients. RESULTS: After statistical analysis,
      the sensitivity of WEnCA was found to be 93%, and the specificity was found to be
      94%. Relapse status and chip results among the stage III CRC patients receiving
      FOLFOX-4 plus cetuximab (n = 59) and those receiving FOLFOX-4 alone (n = 29) were
      compared. Among the 51 stage III CRC patients with chip negative results who were
      treated with FOLFOX-4 plus cetuximab chemotherapy, the relapse rate was 33.3%;
      otherwise, the relapse rate was 48.5% among the 23 out of 88 patients with chip
      negative results who received FOLFOX-4 alone. Negative chip results were
      significantly associated to better treatment outcomes in the FOLFOX-4 plus
      cetuximab group (P = 0.047). CONCLUSIONS: The results demonstrated that the WEnCA
      technique is a sensitive and convenient technique that produces easy-to-interpret
      results for detecting activated KRAS from the peripheral blood of cancer
      patients. We suggest that the WEnCA technique is also a potential tool for
      predicting responses in CRC patients following FOLFOX-4 plus cetuximab
      chemotherapy.

PMID- 24884536
TI  - Plasmonically enhanced electron escape from gold nanoparticles and their
      polarization-dependent excitation transfer along DNA nanowires.
AB  - Here we show plasmon mediated excitation transfer along DNA nanowires over up to
      one micrometer. Apparently, an electron excitation is initiated by a femtosecond
      laser pulse that illuminates gold nanoparticles (AuNP) on double stranded DNA
      (dsDNA). The dependency of this excitation on laser wavelength and polarization
      are investigated. Excitation of the plasmon resonance of the AuNPs via one- and
      two-photon absorption at 520 and 1030 nm, respectively, was explored. We
      demonstrate an excitation transfer along dsDNA molecules at plasmon supported
      four-photon excitation of AuNP cluster or at laser field driven nanoparticle
      electron tunneling for an alignment of the attached dsDNA to the polarization of
      the electric field of the laser light. These results extend the previously
      observed plasmonically induced three-photon excitation transfer along DNA
      nanowires to another nanoparticle material (gold) and the adapted irradiation
      wavelengths. 

PMID- 24884537
TI  - Corticosteroid therapy in regressive autism: Preliminary findings from a
      retrospective study.
AB  - Some children with autism spectrum disorders (ASD; 15% to 30% of patients) show a
      significant and persistent regression in speech and social function during early
      childhood. There are no established treatments for the regressive symptoms.
      However, there are some known causes of this type of regression, such as Rett
      syndrome and Landau-Kleffner syndrome (LKS). In LKS, steroids have been used as a
      treatment. Some evidence suggests an autoimmune contribution to the
      pathophysiology of autism (Chez MG, Guido-Estrada N: Immune therapy in autism:
      historical experience and future directions with immunomodulatory therapy.
      Neurotherapeutics 2010, 7:293-301, Wasilewska J, Kaczmarski M, Stasiak-Barmuta A,
      Tobolczyk J, Kowalewska E: Low serum IgA and increased expression of CD23 on B
      lymphocytes in peripheral blood in children with regressive autism aged 3-6 years
      old. Arch Med Sci 2012, 8:324-331, Stefanatos G: Changing perspectives on Landau
      Kleffner syndrome. Clin Neuropsychol 2011, 25:963-988), raising the possibility
      that steroids might be a useful therapy for regression in ASD. A retrospective
      study published in BMC Neurology by Duffy et al. (Duffy, et al: Corticosteroid
      therapy in regressive autism: A retrospective study of effects on the Frequency
      Modulated Auditory Evoked Response (FMAER), language, and behavior. BMC Neurol
      2014, 14:70) reviewed 20 steroid treated R-ASD (STAR) patients and 24 ASD control
      patients not treated with steroids (NSA). Improvements in clinical function and
      in a neurophysiological biomarker were seen in the steroid-treated children pre-
      to post-prednisolone treatment. This research provides a rationale for a
      randomized trial with steroid therapy to determine the longer term benefits and
      complications of steroids in this population.

PMID- 24884538
TI  - Deconstructing pheromone-mediated behavior one layer at a time.
AB  - The vomeronasal organ, a sensory structure within the nasal cavity of most
      tetrapods, detects pheromones that influence socio-sexual behavior. It has two
      neuronal layers, each patterned by distinct receptor sub-families coupled to
      different G-proteins. Work recently published in this journal found female mice
      with one layer genetically inactivated are deficient in a surprisingly wide range
      of reproductive behaviors, providing new insights into how the nose can influence
      the brain.

PMID- 24884539
TI  - Reimbursement of hormonal contraceptives and the frequency of induced abortion
      among teenagers in Sweden.
AB  - BACKGROUND: Reduction in costs of hormonal contraceptives is often proposed to
      reduce rates of induced abortion among young women. This study investigates the
      relationship between rates of induced abortion and reimbursement of dispensed
      hormonal contraceptives among young women in Sweden. Comparisons are made with
      the Nordic countries Finland, Norway and Denmark. METHODS: Official statistics on
      induced abortion and numbers of prescribed and dispensed hormonal contraceptives
      presented as "Defined Daily Dose/thousand women" (DDD/T) aged 15-19 years were
      compiled and related to levels of reimbursement in all Swedish counties by using
      public official data. The Swedish numbers of induced abortion were compared to
      those of Finland, Norway and Denmark. The main outcome measure was rates of
      induced abortion and DDD/T. RESULTS: No correlation was observed between rates of
      abortion and reimbursement among Swedish counties. Nor was any correlation found
      between sales of hormonal contraceptives and the rates of abortion. In a Nordic
      perspective, Finland and Denmark, which have no reimbursement at all, and Norway
      all have lower rates of induced abortion than Sweden. CONCLUSIONS: Reimbursement
      does not seem to be enough in order to reduce rates of induced abortion.
      Evidently, other factors such as attitudes, education, religion, tradition or
      cultural differences in each of Swedish counties as well as in the Nordic
      countries may be of importance. A more innovative approach is needed in order to
      facilitate safe sex and to protect young women from unwanted pregnancies.

PMID- 24884540
TI  - The HMITM module: a new tool to study the Host-Microbiota Interaction in the
      human gastrointestinal tract in vitro.
AB  - BACKGROUND: Recent scientific developments have shed more light on the importance
      of the host-microbe interaction, particularly in the gut. However, the
      mechanistic study of the host-microbe interplay is complicated by the intrinsic
      limitations in reaching the different areas of the gastrointestinal tract (GIT)
      in vivo. In this paper, we present the technical validation of a new device--the
      Host-Microbiota Interaction (HMI) module--and the evidence that it can be used in
      combination with a gut dynamic simulator to evaluate the effect of a specific
      treatment at the level of the luminal microbial community and of the host surface
      colonization and signaling. RESULTS: The HMI module recreates conditions that are
      physiologically relevant for the GIT: i) a mucosal area to which bacteria can
      adhere under relevant shear stress (3 dynes cm(-2)); ii) the bilateral transport
      of low molecular weight metabolites (4 to 150 kDa) with permeation coefficients
      ranging from 2.4 * 10(-6) to 7.1 * 10(-9) cm sec(-1); and iii) microaerophilic
      conditions at the bottom of the growing biofilm (PmO2 = 2.5 * 10(-4) cm sec(-1)).
      In a long-term study, the host's cells in the HMI module were still viable after
      a 48-hour exposure to a complex microbial community. The dominant mucus
      associated microbiota differed from the luminal one and its composition was
      influenced by the treatment with a dried product derived from yeast fermentation.
      The latter--with known anti-inflammatory properties--induced a decrease of pro
      inflammatory IL-8 production between 24 and 48 h. CONCLUSIONS: The study of the
      in vivo functionality of adhering bacterial communities in the human GIT and of
      the localized effect on the host is frequently hindered by the complexity of
      reaching particular areas of the GIT. The HMI module offers the possibility of co
      culturing a gut representative microbial community with enterocyte-like cells up
      to 48 h and may therefore contribute to the mechanistic understanding of host
      microbiome interactions.

PMID- 24884541
TI  - The influence of pericardial fat upon left ventricular function in obese females:
      evidence of a site-specific effect.
AB  - BACKGROUND: Although increased volume of pericardial fat has been associated with
      decreased cardiac function, it is unclear whether this association is mediated by
      systemic overall obesity or direct regional fat interactions. We hypothesized
      that if local effects dominate, left ventricular (LV) function would be most
      strongly associated with pericardial fat that surrounds the left rather than the
      right ventricle (RV). METHODS: Female obese subjects (n = 60) had cardiovascular
      magnetic resonance (CMR) scans to obtain measures of LV function and pericardial
      fat volumes. LV function was obtained using the cine steady state free precession
      imaging in short axis orientation. The amount of pericardial fat was determined
      volumetrically by the cardiac gated T1 black blood imaging and normalized to body
      surface area. RESULTS: In this study cohort, LV fat correlated with several LV
      hemodynamic measurements including cardiac output (r = -0.41, p = 0.001) and
      stroke volume (r = -0.26, p = 0.05), as well as diastolic functional parameters
      including peak-early-filling rate (r = -0.38, p = 0.01), early late filling ratio
      (r = -0.34, p = 0.03), and time to peak-early-filling (r = 0.34, p = 0.03). These
      correlations remained significant even after adjusting for the body mass index
      and the blood pressure. However, similar correlations became weakened or even
      disappeared between RV fat and LV function. LV function was not correlated with
      systemic plasma factors, such as C-reactive protein (CRP), B-type natriuretic
      peptide (BNP), Interleukin-6 (IL-6), resistin and adiponectin (all p > 0.05).
      CONCLUSIONS: LV hemodynamic and diastolic function was associated more with LV
      fat as compared to RV or total pericardial fat, but not with systemic
      inflammatory markers or adipokines. The correlations between LV function and
      pericardial fat remained significant even after adjusting for systemic factors.
      These findings suggest a site-specific influence of pericardial fat on LV
      function, which could imply local secretion of molecules into the underlying
      tissue or an anatomic effect, both mechanisms meriting future evaluation.

PMID- 24884542
TI  - Focus on vulnerable populations and promoting equity in health service
      utilization--an analysis of visitor characteristics and service utilization of
      the Chinese community health service.
AB  - BACKGROUND: Community health service in China is designed to provide a convenient
      and affordable primary health service for the city residents, and to promote
      health equity. Based on data from a large national study of 35 cities across
      China, we examined the characteristics of the patients and the utilization of
      community health institutions (CHIs), and assessed the role of community health
      service in promoting equity in health service utilization for community
      residents. METHODS: Multistage sampling method was applied to select 35 cities in
      China. Four CHIs were randomly chosen in every district of the 35 cities. A total
      of 88,482 visitors to the selected CHIs were investigated by using intercept
      survey method at the exit of the CHIs in 2008, 2009, 2010, and 2011. Descriptive
      analyses were used to analyze the main characteristics (gender, age, and income)
      of the CHI visitors, and the results were compared with that from the National
      Health Services Survey (NHSS, including CHIs and higher levels of hospitals). We
      also analyzed the service utilization and the satisfactions of the CHI visitors.
      RESULTS: The proportions of the children (2.4%) and the elderly (about 22.7%)
      were lower in our survey than those in NHSS (9.8% and 38.8% respectively). The
      proportion of the low-income group (26.4%) was apparently higher than that in
      NHSS (12.5%). The children group had the lowest satisfaction with the CHIs than
      other age groups. The satisfaction of the low-income visitors was slightly higher
      than that of the higher-income visitors. The utilization rate of public health
      services was low in CHIs. CONCLUSIONS: The CHIs in China appears to fulfill the
      public health target of uptake by vulnerable populations, and may play an
      important role in promoting equity in health service utilization. However,
      services for children and the elderly should be strengthened.

PMID- 24884543
TI  - Is a single item stress measure independently associated with subsequent severe
      injury: a prospective cohort study of 16,385 forest industry employees.
AB  - BACKGROUND: A previous review showed that high stress increases the risk of
      occupational injury by three- to five-fold. However, most of the prior studies
      have relied on short follow-ups. In this prospective cohort study we examined the
      effect of stress on recorded hospitalised injuries in an 8-year follow-up.
      METHODS: A total of 16,385 employees of a Finnish forest company responded to the
      questionnaire. Perceived stress was measured with a validated single-item
      measure, and analysed in relation recorded hospitalised injuries from 1986 to
      2008. We used Cox proportional hazard regression models to examine the
      prospective associations between work stress, injuries and confounding factors.
      RESULTS: Highly stressed participants were approximately 40% more likely to be
      hospitalised due to injury over the follow-up period than participants with low
      stress. This association remained significant after adjustment for age, gender,
      marital status, occupational status, educational level, and physical work
      environment. CONCLUSIONS: High stress is associated with an increased risk of
      severe injury.

PMID- 24884544
TI  - Patient reported outcome measures (PROMs) in primary care: an observational pilot
      study of seven generic instruments.
AB  - BACKGROUND: Patient reported outcome measures (PROMs) have been introduced in
      studies to assess healthcare performance. The development of PROMs for primary
      care poses specific challenges, including a preference for generic measures that
      can be used across diseases, including early phases or mild conditions. This
      pilot study aimed to explore the potential usefulness of seven generic measures
      for assessing health outcomes in primary care patients. METHODS: A total of 300
      patients in three general practices were invited to participate in the study,
      shortly after their visit to the general practitioner. Patients received a
      written questionnaire, containing seven validated instruments, focused on patient
      empowerment (PAM-13 or EC-17), quality of life (EQ-5D or SF-12), mental health
      (GHQ-12), enablement (PEI) and perceived treatment effect (GPE). Furthermore,
      questions on non-specific symptoms and number of GP contacts were included. After
      4 weeks patients received a second, identical, questionnaire. Response and
      missing items, total scores and dispersion, responsiveness, and associations
      between instruments and other measures were examined. RESULTS: A total of 124
      patients completed the questionnaire at baseline, of whom 98 completed it both at
      baseline and 4 weeks later (response rate: 32.7%). The instruments had a full
      completion rate of 80% or higher. Differences between baseline and follow up were
      significant for the EQ-5D (p=0.026), SF-12 PCS (p=0.026) and the GPE (p=0.006). A
      strong correlation (r >= 0.6) was found between the SF-12 MCS and GHQ-12, at both
      baseline measurement and after four weeks. Other observed associations between
      instruments were moderately strong. No strong correlations were found between
      instruments and non-specific symptoms or number of GP contacts. CONCLUSIONS: The
      present study is among the first to explore the use of generic patient-reported
      outcome measures in primary care. It provides several leads for developing a
      generic PROM questionnaire in primary care as well as for potential limitations
      of such instruments.

PMID- 24884545
TI  - Speeding in school zones: violation or lapse in prospective memory?
AB  - Inappropriate speed is a causal factor in around one third of fatal accidents
      (OECD/ECMT, 2006). But are drivers always consciously responsible for their
      speeding behavior? Two studies are reported which show that an interruption to a
      journey, caused by stopping at a red traffic light, can result in failure to
      resume the speed of travel prior to the interruption (Study 1). In Study 2 we
      showed that the addition of a reminder cue could offset this interruption. These
      studies were conducted in a number of Australian school zone sites subject to a
      40 km/h speed limit, requiring a reduction of between 20 km/h and 40 km/h.
      Motorists who had stopped at a red traffic signal sped on average, 8.27 km/h over
      the speed limit compared with only 1.76 km/h over the limit for those who had not
      been required to stop. In the second study a flashing "check speed" reminder cue,
      placed 70 m after the traffic lights, in the same school zones as those in Study
      1 eliminated the interruptive effect of stopping with drivers resuming their
      journey at the legal speed. These findings have practical implications for the
      design of road environments, enforcement of speed limits, and the safety of
      pedestrians.

PMID- 24884546
TI  - Altered mucosal immune response after acute lung injury in a murine model of
      Ataxia Telangiectasia.
AB  - BACKGROUND: Ataxia telangiectasia (A-T) is a rare but devastating and progressive
      disorder characterized by cerebellar dysfunction, lymphoreticular malignancies
      and recurrent sinopulmonary infections. In A-T, disease of the respiratory system
      causes significant morbidity and is a frequent cause of death. METHODS: We used a
      self-limited murine model of hydrochloric acid-induced acute lung injury (ALI) to
      determine the inflammatory answer due to mucosal injury in Atm (A-T mutated)-
      deficient mice (Atm(-/-)). RESULTS: ATM deficiency increased peak lung
      inflammation as demonstrated by bronchoalveolar lavage fluid (BALF) neutrophils
      and lymphocytes and increased levels of BALF pro-inflammatory cytokines (e.g. IL
      6, TNF). Furthermore, bronchial epithelial damage after ALI was increased in Atm(
      /-) mice. ATM deficiency increased airway resistance and tissue compliance before
      ALI was performed. CONCLUSIONS: Together, these findings indicate that ATM plays
      a key role in inflammatory response after airway mucosal injury.

PMID- 24884547
TI  - Web-based therapeutic exercise resource center as a treatment for knee
      osteoarthritis: a prospective cohort pilot study.
AB  - BACKGROUND: Although beneficial effects of exercise in the management of knee
      osteoarthritis (OA) have been established, only 14 -18% of patients with knee OA
      receive an exercise from their primary care provider. Patients with knee OA cite
      lack of physician exercise advice as a major reason why they do not exercise to
      improve their condition. The purpose of this pilot study was to investigate use
      of a web-based Therapeutic Exercise Resource Center (TERC) as a tool to prescribe
      strength, flexibility and aerobic exercise as part of knee OA treatment. It was
      hypothesized that significant change in clinical outcome scores would result from
      patients' use of the TERC. METHODS: Sixty five individuals diagnosed with
      mild/moderate knee OA based on symptoms and radiographs were enrolled through
      outpatient physician clinics. Using exercise animations to facilitate proper
      technique, the TERC assigned and progressed patients through multiple levels of
      exercise intensity based on exercise history, co-morbidities and a validated
      measure of pain and function. Subjects completed a modified short form WOMAC (mSF
      WOMAC), World Health Organization Quality of Life (WHO-QOL) and Knee Self
      Efficacy Scale (K-SES) at baseline and completion of the 8 week program, and a
      user satisfaction survey. Outcomes were compared over time using paired t-tests
      and effect sizes calculated using partial point biserial (pr). RESULTS: Fifty two
      participants completed the 8 week program with average duration of knee pain 8.0
      +/- 11.0 yrs (25 females; 61.0 +/- 9.4 yrs; body mass index, 28.8 +/- 6.3 kg/m2).
      During the study period, all outcome measures improved: mSF-WOMAC scores
      decreased (better pain and function) (p<.001; large effect, pr=0.70); WHO-QOL
      physical scores increased (p=.015; medium effect, pr=0.33); and K-SES scores
      increased (p<.001; large effect, pr=0.54). No significant differences were found
      in study outcomes as a function of gender, age, BMI or symptom duration. Patients
      reported very positive evaluation of the TERC (94% indicated the website was easy
      to use; 90% specified the exercise animations were especially helpful).
      CONCLUSION: This pilot study demonstrated the web-based TERC to be feasible and
      efficacious in improving clinical outcomes for patients with mild/moderate knee
      OA and supports future studies to compare TERC to current standard of care, such
      as educational brochures.

PMID- 24884548
TI  - Role of anti-inflammatory compounds in human immunodeficiency virus-1
      glycoprotein120-mediated brain inflammation.
AB  - BACKGROUND: Neuroinflammation is a common immune response associated with brain
      human immunodeficiency virus-1 (HIV-1) infection. Identifying therapeutic
      compounds that exhibit better brain permeability and can target signaling
      pathways involved in inflammation may benefit treatment of HIV-associated
      neurological complications. The objective of this study was to implement an in
      vivo model of brain inflammation by intracerebroventricular administration of the
      HIV-1 viral coat protein gp120 in rats and to examine anti-inflammatory
      properties of HIV adjuvant therapies such as minocycline, chloroquine and
      simvastatin. METHODS: Male Wistar rats were administered a single dose of
      gp120ADA (500 ng) daily for seven consecutive days, intracerebroventricularly,
      with or without prior intraperitoneal administration of minocycline, chloroquine
      or simvastatin. Maraviroc, a CCR5 antagonist, was administered
      intracerebroventricularly prior to gp120 administration for seven days as
      control. Real-time qPCR was used to assess gene expression of inflammatory
      markers in the frontal cortex, hippocampus and striatum. Interleukin-1beta (IL
      1beta) and tumor necrosis factor-alpha (TNF-alpha) secretion in cerebrospinal
      fluid (CSF) was measured applying ELISA. Protein expression of mitogen-activated
      protein kinases (MAPKs) (extracellular signal-related kinase 1/2 (ERK1/2), c-Jun
      N-terminal kinases (JNKs) and P38 kinases (P38Ks)) was detected using immunoblot
      analysis. Student's t-test and ANOVA were applied to determine statistical
      significance. RESULTS: In gp120ADA-injected rats, mRNA transcripts of interleukin
      1beta (IL-1beta) and inducible nitric oxide synthase (iNOS) were significantly
      elevated in the frontal cortex, striatum and hippocampus compared to saline or
      heat-inactivated gp120-injected controls. In CSF, a significant increase in TNF
      alpha and IL-1beta was detected. Maraviroc reduced upregulation of these markers
      suggesting that the interaction of R5-tropic gp120 to CCR5 chemokine receptor is
      critical for induction of an inflammatory response. Minocycline, chloroquine or
      simvastatin attenuated upregulation of IL-1beta and iNOS transcripts in different
      brain regions. In CSF, minocycline suppressed TNF-alpha and IL-1beta secretion,
      whereas chloroquine attenuated IL-1beta secretion. In gp120-injected animals,
      activation of ERK1/2 and JNKs was observed in the hippocampus and ERK1/2
      activation was significantly reduced by the anti-inflammatory agents.
      CONCLUSIONS: Our data demonstrate that anti-inflammatory compounds can completely
      or partially reverse gp120-associated brain inflammation through an interaction
      with MAPK signaling pathways and suggest their potential role in contributing
      towards the prevention and treatment of HIV-associated neurological
      complications.

PMID- 24884549
TI  - The impact of headache in Europe: principal results of the Eurolight project.
AB  - BACKGROUND: European data, at least from Western Europe, are relatively good on
      migraine prevalence but less sound for tension-type headache (TTH) and medication
      overuse headache (MOH). Evidence on impact of headache disorders is very limited.
      Eurolight was a data-gathering exercise primarily to inform health policy in the
      European Union (EU). This manuscript reports personal impact. METHODS: The study
      was cross-sectional with modified cluster sampling. Surveys were conducted by
      structured questionnaire, including diagnostic questions based on ICHD-II and
      various measures of impact, and are reported from Austria, France, Germany,
      Italy, Lithuania, Luxembourg, Netherlands, Spain and United Kingdom. Different
      methods of sampling were used in each. The full methodology is described
      elsewhere. RESULTS: Questionnaires were analysed from 8,271 participants (58%
      female, mean age 43.4 y). Participation-rates, where calculable, varied from
      10.6% to 58.8%. Moderate interest-bias was detected. Unadjusted lifetime
      prevalence of any headache was 91.3%. Gender-adjusted 1-year prevalences were:
      any headache 78.6%; migraine 35.3%; TTH 38.2%, headache on >=15 d/mo 7.2%;
      probable MOH 3.1%. Personal impact was high, and included ictal symptom burden,
      interictal burden, cumulative burden and impact on others (partners and
      children). There was a general gradient of probable MOH > migraine > TTH, and
      most measures indicated higher impact among females. Lost useful time was
      substantial: 17.7% of males and 28.0% of females with migraine lost >10% of days;
      44.7% of males and 53.7% of females with probable MOH lost >20%. CONCLUSIONS: The
      common headache disorders have very high personal impact in the EU, with
      important implications for health policy.

PMID- 24884550
TI  - Testing the treatment effect on competing causes of death in oncology clinical
      trials.
AB  - BACKGROUND: Chemotherapy is expected to reduce cancer deaths (CD), while possibly
      being harmful in terms of non-cancer deaths (NCD) because of toxicity. Peto's log
      rank test is popular in the medical literature, but its operating characteristics
      are barely known. We compared this test to the most common ones in the
      statistical literature: the cause-specific hazard test and Gray's test on the
      hazard of the subdistribution. We investigated for the first time the impact of
      reclassifications of causes of death (CoD) after recurrences, and of
      misclassification of CoD. METHODS: We present a simulation study in which we
      varied the censoring rate and the correlation between CD and NCD times, we
      generated recurrence times to study the role of the reclassification of CoD, and
      we added 20% misclassified CoD. We considered four scenarios for the treatment
      effect: none; none for CD and negative for NCD; positive for CD and none for NCD;
      positive for CD and negative for NCD. We applied the three tests to a randomized
      clinical trial evaluating adjuvant chemotherapy in 1,867 patients with non-small
      cell lung cancer. RESULTS: Most often the three tests well preserved their
      nominal size, Gray's test did not when the treatment had an effect on the
      competing CoD. With a high rate of misclassified CoD, Gray's and the cause
      specific tests lost much of their power, whereas the Peto's test had the highest
      power. The cause-specific test had inflated size for NCD when the treatment was
      beneficial for CD with many misclassified CoD, but had the highest power for NCD
      when the treatment had no effect on CD, and had similar power to Peto's test for
      CD when the treatment had no effect on NCD. Gray's test performed best when the
      effect on the two CoD was opposite. The higher the censoring, the lower the
      rejection probabilities of all the tests and the smaller their differences.
      CONCLUSIONS: In this first head-to-head comparison of the three tests, the cause
      specific test often proved to be the most reliable. Comparing results with and
      without misclassification of the CoD, Peto's test was the least influenced by the
      presence of such misclassification.

PMID- 24884553
TI  - Gathering of wild food plants in anthropogenic environments across the seasons:
      implications for poor and vulnerable farm households.
AB  - This article presents the results of a study conducted in Northeast Thailand on
      wild food plant gathering in anthropogenic areas and the implications for
      vulnerable households. A sub-sample of 40 farming households was visited every
      month to conduct seven-day recalls over a 12-month period on wild food plant
      acquisition events. Results show that these plants are an essential part of the
      diet, constituting a "rural safety net" particularly for vulnerable households.
      Findings reveal that anthropogenic environments have seasonal complementarity
      throughout the year with respect to wild food gathering and farmer's gathering of
      wild food plants from anthropogenic environments complements seasonal crop
      availability. This study contributes to a deeper understanding of these plants as
      a household asset and their potential contribution to household well-being. The
      results of this study furthers our understanding of dietary traditions and the
      scientific challenge of the partitions that have for decades divided
      agriculturalists and gatherers. 

PMID- 24884552
TI  - Environmental influences on youth eating habits: insights from parents and
      teachers in South Korea.
AB  - Youth obesity has increased over the past two decades in South Korea. Researchers
      employed in-depth interviews and focus-group discussions with parents and
      teachers from 26 schools in metropolitan South Korea, to examine environmental
      factors affecting youth eating habits. Home environment and exposure to healthy
      foods were the most important factors influencing healthy eating habits. Families
      with working mothers eat out more than do families with stay-at-home mothers.
      Poor nutrition education is associated with low vegetable intake in elementary
      school lunches. A cultural emphasis on academic achievement adversely affects
      children's eating practices. Findings can guide future studies and inform program
      development. 

PMID- 24884551
TI  - Resistance to simian immunodeficiency virus low dose rectal challenge is
      associated with higher constitutive TRIM5alpha expression in PBMC.
AB  - BACKGROUND: At least six host-encoded restriction factors (RFs), APOBEC3G,
      TRIM5alpha, tetherin, SAMHD1, schlafen 11, and Mx2 have now been shown to inhibit
      HIV and/or SIV replication in vitro. To determine their role in vivo in the
      resistance of macaques to mucosally-acquired SIV, we quantified both pre-exposure
      (basal) and post-exposure mRNA levels of these RFs, Mx1, and IFNgamma in PBMC,
      lymph nodes, and duodenum of rhesus macaques undergoing weekly low dose rectal
      exposures to the primary isolate, SIV/DeltaB670. RESULTS: Repetitive challenge
      divided the monkeys into two groups with respect to their susceptibility to
      infection: highly susceptible (2-3 challenges, 5 monkeys) and poorly susceptible
      (>=6 challenges, 3 monkeys). Basal RF and Mx1 expression varied among the three
      tissues examined, with the lowest expression generally detected in duodenal
      tissues, and the highest observed in PBMC. The one exception was A3G whose basal
      expression was greatest in lymph nodes. Importantly, significantly higher basal
      expression of TRIM5alpha and Mx1 was observed in PBMC of animals more resistant
      to mucosal infection. Moreover, individual TRIM5alpha levels were stable
      throughout a year prior to infection. Post-exposure induction of these genes was
      also observed after virus appearance in plasma, with elevated levels in PBMC and
      duodenum transiently occurring 7-10 days post infection. They did not appear to
      have an effect on control of viremia. Interestingly, minimal to no induction was
      observed in the resistant animal that became an elite controller. CONCLUSIONS:
      These results suggest that constitutively expressed TRIM5alpha appears to play a
      greater role in restricting mucosal transmission of SIV than that associated with
      type I interferon induction following virus entry. Surprisingly, this association
      was not observed with the other RFs. The higher basal expression of TRIM5alpha
      observed in PBMC than in duodenal tissues emphasizes the understated role of the
      second barrier to systemic infection involving the transport of virus from the
      mucosal compartment to the blood. Together, these observations provide a strong
      incentive for a more comprehensive examination of the intrinsic, variable control
      of constitutive expression of these genes in the sexual transmission of HIV.

PMID- 24884554
TI  - Indigenous knowledge on landraces and fonio-based food in Benin.
AB  - Fonio is a traditional cereal cultivated in many West African countries, where
      farmers are often the guardians of a rich diversity of landraces or traditional
      varieties. An investigation conducted in northwest of Benin on indigenous
      knowledge about fonio landraces and fonio-based traditional foods allowed us to
      inventory 35 landraces identified by the farmers. Ipormoa, Namba, Icantoni or
      Kopognake or Icantoga and Iporhouwan landraces were good to cook paste and
      couscous and easy to dehusk. Besides, Ipormoa and Iporhouwan landraces had
      interesting agronomic characteristics. Paste, porridge, and couscous were the
      main fonio-based foods consumed by farmers in northwest of Benin. 

PMID- 24884555
TI  - Nutritional habits of mothers and children in the age group 0-4 years in Iran.
AB  - Maternal education and attitudes and practices can significantly be associated
      with the child's nutritional outcomes. Our goal was to find out patterns among
      mothers and children in the context of beliefs, knowledge and cultural practices
      of Iranian mothers. This research provides primary descriptive statistical data.
      To administer the interviews, five hospitals in Tehran, Iran (operating in mother
      and child medical services) were selected. 190 mothers and their children were
      selected for the study. Forty seven mothers (24.7%) were giving cow milk, while
      92 (48.4 %) were giving powdered milk and milk itself 49 remaining (25.8%) gave a
      mixture of breast and cow milk to their children below one year. The
      anthropometric results in majority of the children fell under Grade-I and Grade
      II undernourished category, and that the prevalence of under-nutrition was more
      obvious in lower age group children. A majority of the children were
      undernourished. Poor quality and inadequacy of food intake, economy below
      subsistence level and poor income, and seasonal food shortage were known to cause
      under-nutrition. Numerous factors, such as social, economic, regional, ethnical,
      religious, and superstition affect the mother and child. 

PMID- 24884557
TI  - Nutritional profiles of urban and rural men of Punjab with regard to dietary fat
      intake.
AB  - This study was undertaken to determine the quantity and type of fat consumed by
      urban and rural men in relation to BMI. Researchers surveyed 200 Punjabi men from
      rural and urban areas of Ludhiana District; total fat intake (74 g/day) by urban
      men was significantly more than that of men in rural areas. The energy percentage
      from total fat was positively and significantly (p <= .05) associated with BMI,
      accounting for 3.1%, 4.2%, and 2.9% of variation in the rural, urban, and total
      sample, respectively. Fatty-acid ratios were closer to recommendations for urban
      men than for men from rural areas. 

PMID- 24884556
TI  - Length of migration and eating habits of Portuguese university students living in
      London, United Kingdom.
AB  - Several studies have pointed adverse effects of long term migration on eating
      habits. Research is needed to understand if this effect occurs also with a short
      length of migration, as is the case of international students. Our aim was to
      evaluate the effect of short and long term migration on eating habits of
      Portuguese university students. Participants were 46 English and 55 Portuguese
      students from universities in London, United Kingdom. The findings from this
      study highlight the difficulties that Portuguese students faced in maintaining a
      traditional Mediterranean diet after moving to a Northern European environment. 

PMID- 24884558
TI  - Fisheries productivity and its effects on the consumption of animal protein and
      food sharing of fishers' and non-fishers' families.
AB  - This study compared the consumption of animal protein and food sharing among
      fishers' and non-fishers' families of the northeastern Brazilian coast. The diet
      of these families was registered through the 24-hour-recall method during 10
      consecutive days in January (good fishing season) and June (bad fishing season)
      2012. Fish consumption was not different between the fishers' and non-fishers'
      families, but varied according to fisheries productivity to both groups.
      Likewise, food sharing was not different between the two groups, but food was
      shared more often when fisheries were productive. Local availability of fish,
      more than a direct dependency on fisheries, determines local patterns of animal
      protein consumption, but a direct dependency on fisheries exposes families to a
      lower-quality diet in less-productive seasons. As such, fisheries could shape and
      affect the livelihoods of coastal villages, including fishers' and non-fishers'
      families. 

PMID- 24884559
TI  - Urethral metastasis from a sigmoid colon carcinoma: a quite rare case report and
      review of the literature.
AB  - BACKGROUND: Urethral metastatic adenocarcinoma is extremely rare. Moreover, only
      9 previous cases with metastases from colorectal cancer have been reported to
      date, and not much information on urethral metastases from colorectum is
      available so far. CASE PRESENTATION: We report our experience in the diagnosis
      and the management of the case with urethral metastasis from a sigmoid colon
      cancer. A 68-year-old man, who underwent laparoscopic sigmoidectomy for sigmoid
      colon carcinoma four years ago, presented gross hematuria with pain. Urethroscopy
      identified a papillo-nodular tumor 7 mm in diameter in the bulbar urethra. CT
      scan imaging revealed the small mass of bulbous portion of urethra and solitary
      lung metastasis. Histological examination of the tumor obtained by transurethral
      resection showed moderately differentiated adenocarcinoma, which was diagnosed as
      a metastasis of a sigmoid colon carcinoma pathologically by morphological
      examination. Immunohistochemical analysis of the urethral tumor revealed the
      positive for cytokertin 20 and CDX2, whereas negative for cytokertin 7. These
      features were consistent with metastatic adenocarcinoma of the sigmoid colon
      cancer. As the management of this case with urethral and lung metastasis, 6-cycle
      of chemotherapy with fluorouracil with leucovorin plus oxaliplatin was
      administered to the patient, and these metastases were disappeared with no
      recurrence of disease for 34 months. CONCLUSION: Urethral metastasis from
      colorectal cancer is a very rare occurrence. However, in the presence of urinary
      symptoms, the possibility of the urethral metastasis should be considered.

PMID- 24884560
TI  - Financial impact of adopting implantable loop recorder diagnostic for unexplained
      syncope compared with conventional diagnostic pathway in Portugal.
AB  - BACKGROUND: To estimate the short- and long-term financial impact of early
      referral for implantable loop recorder diagnostic (ILR) versus conventional
      diagnostic pathway (CDP) in the management of unexplained syncope (US) in the
      Portuguese National Health Service (PNHS). METHODS: A Markov model was developed
      to estimate the expected number of hospital admissions due to US and its
      respective financial impact in patients implanted with ILR versus CDP. The
      average cost of a syncope episode admission was estimated based on Portuguese
      cost data and landmark papers. The financial impact of ILR adoption was estimated
      for a total of 197 patients with US, based on the number of syncope admissions
      per year in the PNHS. Sensitivity analysis was performed to take into account the
      effect of uncertainty in the input parameters (hazard ratio of death; number of
      syncope events per year; probabilities and unit costs of each diagnostic test;
      probability of trauma and yield of diagnosis) over three-year and lifetime
      horizons. RESULTS: The average cost of a syncope event was estimated to be
      between 1,760? and 2,800?. Over a lifetime horizon, the total discounted costs of
      hospital admissions and syncope diagnosis for the entire cohort were 23% lower
      amongst patients in the ILR group compared with the CDP group (1,204,621? for
      ILR, versus 1,571,332? for CDP). CONCLUSION: The utilization of ILR leads to an
      earlier diagnosis and lower number of syncope hospital admissions and
      investigations, thus allowing significant cost offsets in the Portuguese setting.
      The result is robust to changes in the input parameter values, and cost savings
      become more pronounced over time.

PMID- 24884561
TI  - Natural transformation of Thermotoga sp. strain RQ7.
AB  - BACKGROUND: Thermotoga species are organisms of enormous interest from a
      biotechnological as well as evolutionary point of view. Genetic modifications of
      Thermotoga spp. are often desired in order to fully release their multifarious
      potentials. Effective transformation of recombinant DNA into these bacteria
      constitutes a critical step of such efforts. This study aims to establish natural
      competency in Thermotoga spp. and to provide a convenient method to transform
      these organisms. RESULTS: Foreign DNA was found to be relatively stable in the
      supernatant of a Thermotoga culture for up to 6 hours. Adding donor DNA to T. sp.
      strain RQ7 at its early exponential growth phase (OD600 0.18 ~ 0.20) resulted in
      direct acquisition of the DNA by the cells. Both T. neapolitana chromosomal DNA
      and Thermotoga-E. coli shuttle vectors effectively transformed T. sp. strain RQ7,
      rendering the cells resistance to kanamycin. The kan gene carried by the shuttle
      vector pDH10 was detected by PCR from the plasmid extract of the transformants,
      and the amplicons were verified by restriction digestions. A procedure for
      natural transformation of Thermotoga spp. was established and optimized. With the
      optimized method, T. sp. strain RQ7 sustained a transformation frequency in the
      order of 10-7 with both genomic and plasmid DNA. CONCLUSIONS: T. sp. strain RQ7
      cells are naturally transformable during their early exponential phase. They
      acquire DNA from both closely and distantly related species. Both chromosomal DNA
      and plasmid DNA serve as suitable substrates for transformation. Our findings
      lend a convenient technical tool for the genetic engineering of Thermotoga spp.

PMID- 24884562
TI  - The effect of rituximab therapy on immunoglobulin levels in patients with
      multisystem autoimmune disease.
AB  - BACKGROUND: Rituximab is a B cell depleting anti-CD20 monoclonal antibody. CD20
      is not expressed on mature plasma cells and accordingly rituximab does not have
      immediate effects on immunoglobulin levels. However, after rituximab some
      patients develop hypogammaglobulinaemia. METHODS: We performed a single centre
      retrospective review of 177 patients with multisystem autoimmune disease
      receiving rituximab between 2002 and 2010. The incidence, severity and
      complications of hypogammaglobulinaemia were investigated. RESULTS: Median
      rituximab dose was 6 g (1-20.2) and total follow-up was 8012 patient-months. At
      first rituximab, the proportion of patients with IgG <6 g/L was 13% and remained
      stable at 17% at 24 months and 14% at 60 months. Following rituximab, 61/177
      patients (34%) had IgG <6 g/L for at least three consecutive months, of whom
      7/177 (4%) had IgG <3 g/L. Low immunoglobulin levels were associated with higher
      glucocorticoid doses during follow up and there was a trend for median IgG levels
      to fall after >= 6 g rituximab. 45/115 (39%) with IgG >= 6 g/L versus 26/62 (42%)
      with IgG <6 g/L experienced severe infections (p=0.750). 6/177 patients (3%)
      received intravenous immunoglobulin replacement therapy, all with IgG <5 g/L and
      recurrent infection. CONCLUSIONS: In multi-system autoimmune disease, prior
      cyclophosphamide exposure and glucocorticoid therapy but not cumulative rituximab
      dose was associated with an increased incidence of hypogammaglobulinaemia. Severe
      infections were common but were not associated with immunoglobulin levels. Repeat
      dose rituximab therapy appears safe with judicious monitoring.

PMID- 24884563
TI  - Natural course of care dependency in residents of long-term care facilities:
      prospective follow-up study.
AB  - BACKGROUND: Insight in the natural course of care dependency of vulnerable older
      persons in long-term care facilities (LTCF) is essential to organize and optimize
      individual tailored care. We examined changes in care dependency in LTCF
      residents over two 6-month periods, explored the possible predictive factors of
      change and the effect of care dependency on mortality. METHODS: A prospective
      follow-up study in 21 Dutch long-term care facilities. 890 LTCF residents, median
      age 84 (Interquartile range 79-88) years participated. At baseline, 6 and 12
      months, care dependency was assessed by the nursing staff with the Care
      Dependency Scale (CDS), range 15-75 points. Since the median CDS score differed
      between men and women (47.5 vs. 43.0, P = 0.013), CDS groups (low, middle and
      high) were based on gender-specific 33% of CDS scores at baseline and 6 months.
      RESULTS: At baseline, the CDS groups differed in median length of stay on the
      ward, urine incontinence and dementia (all P < 0.001); participants in the low
      CDS group stayed longer, had more frequent urine incontinence and more dementia.
      They had also the highest mortality rate (log rank 32.2; df = 2; P for trend
      <0.001). Per point lower in CDS score, the mortality risk increased with 2% (95%
      CI 1%-3%). Adjustment for age, gender, cranberry use, LTCF, length of stay,
      comorbidity and dementia showed similar results. A one point decrease in CDS
      score between 0 and 6 months was related to an increased mortality risk of 4%
      (95% CI 3%-6%).At the 6-month follow-up, 10% improved to a higher CDS group, 65%
      were in the same, and 25% had deteriorated to a lower CDS group; a similar
      pattern emerged at 12-month follow-up. Gender, age, urine incontinence, dementia,
      cancer and baseline care dependency status, predicted an increase in care
      dependency over time. CONCLUSION: The majority of residents were stable in their
      care dependency status over two subsequent 6-month periods. Highly care dependent
      residents showed an increased mortality risk. Awareness of the natural course of
      care dependency is essential to residents and their formal and informal
      caregivers when considering therapeutic and end-of-life care options.

PMID- 24884564
TI  - Efficient discovery of responses of proteins to compounds using active learning.
AB  - BACKGROUND: Drug discovery and development has been aided by high throughput
      screening methods that detect compound effects on a single target. However, when
      using focused initial screening, undesirable secondary effects are often detected
      late in the development process after significant investment has been made. An
      alternative approach would be to screen against undesired effects early in the
      process, but the number of possible secondary targets makes this prohibitively
      expensive. RESULTS: This paper describes methods for making this global approach
      practical by constructing predictive models for many target responses to many
      compounds and using them to guide experimentation. We demonstrate for the first
      time that by jointly modeling targets and compounds using descriptive features
      and using active machine learning methods, accurate models can be built by doing
      only a small fraction of possible experiments. The methods were evaluated by
      computational experiments using a dataset of 177 assays and 20,000 compounds
      constructed from the PubChem database. CONCLUSIONS: An average of nearly 60% of
      all hits in the dataset were found after exploring only 3% of the experimental
      space which suggests that active learning can be used to enable more complete
      characterization of compound effects than otherwise affordable. The methods
      described are also likely to find widespread application outside drug discovery,
      such as for characterizing the effects of a large number of compounds or
      inhibitory RNAs on a large number of cell or tissue phenotypes.

PMID- 24884565
TI  - High-resolution crystal structure of spin labelled (T21R1) azurin from
      Pseudomonas aeruginosa: a challenging structural benchmark for in silico spin
      labelling algorithms.
AB  - BACKGROUND: EPR-based distance measurements between spin labels in proteins have
      become a valuable tool in structural biology. The direct translation of the
      experimental distances into structural information is however often impaired by
      the intrinsic flexibility of the spin labelled side chains. Different algorithms
      exist that predict the approximate conformation of the spin label either by using
      pre-computed rotamer libraries of the labelled side chain (rotamer approach) or
      by simply determining its accessible volume (accessible volume approach).
      Surprisingly, comparisons with many experimental distances have shown that both
      approaches deliver the same distance prediction accuracy of about 3 A. RESULTS:
      Here, instead of comparing predicted and experimental distances, we test the
      ability of both approaches to predict the actual conformations of spin labels
      found in a new high-resolution crystal structure of spin labelled azurin (T21R1).
      Inside the crystal, the label is found in two very different environments which
      serve as a challenging test for the in silico approaches. CONCLUSIONS: Our
      results illustrate why simple and more sophisticated programs lead to the same
      prediciton error. Thus, a more precise treatment of the complete environment of
      the label and also its interactions with the environment will be needed to
      increase the accuracy of in silico spin labelling algorithms.

PMID- 24884566
TI  - Single nucleotide polymorphisms in TNFAIP3 were associated with the risks of
      rheumatoid arthritis in northern Chinese Han population.
AB  - BACKGROUND: Rheumatoid arthritis (RA) is a systemic autoimmune disease
      characterized by chronic destructive inflammation in synovial joints. It is well
      known that genetic and environmental risk factors and their interaction
      contribute to RA pathogenesis. This study aimed to investigate the association
      between the critical polymorphisms in the tumor necrosis factor alpha (TNFalpha)
      induced protein 3(TNFAIP3) gene and the risk of RA in a large northern Chinese
      Han population. METHODS: A case-control study of 1280 RA patients and 1280
      matched healthy controls was conducted. RESULTS: This study showed that carriers
      of the rs2230926 TG genotype or rs10499194 CT genotype had an increased risk for
      RA compared with those carrying the wild genotype (rs2230926: OR = 1.48, 95% CI =
      1.17-1.86, p = 0.001; rs10499194: OR = 2.00, 95% CI = 1.46-2.74, p < 0.001). The
      combined rs2230926TG/GG or rs10499194 CT/TT were associated with an increased
      risk of RA (ORs were 1.50 and 2.01, 95% CIs were 1.19-1.88 and 1.47-2.74,
      respectively, both p < 0.001). There was not significant association between
      rs13207033 polymorphism and RA risk. Subset analysis stratified to gender showed
      that the increased risks were significant among the genotypes TG, TG/GG of
      rs2230926 and CT, CT/TT of rs10499194 and the corresponding ORs were 1.42 (95% 
      CI = 1.10-1.83, p = 0.006), 1.44(95% CI = 1.12-1.85, p = 0.004), 1.52(95% CI =
      1.05-2.20, p = 0.026) and 1.52(95% CI = 1.06-2.19, p = 0.023) in the female
      population. Stratified analyses by age found that rs2230926(TG, TG/GG) and
      rs10499194(CT, CT/TT) polymorphisms were associated with RA risks in population
      <=53 years old and among >53 years old only rs10499194(CT, TT, CT/TT)
      polymorphism had significant results. The interaction analysis suggested that
      individuals with both risk genotypes of the two SNPs have a higher elevated risk
      of RA than those with only one of them (ORs were 3.44 compared to 1.74 and 1.35).
      The haplotype results showed that individuals with the rs2230926G-rs13207033G
      rs10499194C haplotype were associated with increased risks of RA (OR = 1.37, 95%
      CI = 1.08-1.74, p = 0.010). CONCLUSIONS: Rs10499194 and rs2230926 polymorphisms
      in the TNFAIP3 gene region may be susceptibility factors for rheumatoid arthritis
      in the northern Chinese Han population.

PMID- 24884568
TI  - An orally active immune adjuvant prepared from cones of Pinus sylvestris,
      enhances the proliferative phase of a primary T cell response.
AB  - BACKGROUND: We have previously demonstrated that an alkaline extract of shredded
      pinecones yields a polyphenylpropanoid polysaccharide complex (PPC) that
      functions as an orally active immune adjuvant. Specifically, oral PPC can boost
      the number of antigen-specific memory CD8+ T cells generated in response to a
      variety of vaccine types (DNA, protein, and dendritic cell) and bias the response
      towards one that is predominately a T helper 1 type. METHODS: An immune response
      was initiated by intraperitoneal injection of mice with Staphylococcus
      enterotoxin B (SEB). A group of mice received PPC by gavage three times per day
      on Days 0 and 1. The draining lymph nodes were analyzed 48-96 h post-injection
      for the numbers of reactive T cells, cytokine production, the generation of
      reactive oxygen species, and apoptotsis. RESULTS: In this study we examined
      whether the ability of PPC to boost a T cell response is due to an effect on the
      proliferative or contraction phases, or both, of the primary response. We present
      data to demonstrate that oral PPC significantly enhances the primary T cell
      response by affecting the expansion of T cells (both CD4 and CD8) during the
      proliferative phase, while having no apparent effects on the activation-induced
      cell death associated with the contraction phase. CONCLUSIONS: These findings
      suggest that PPC could potentially be utilized to enhance the T cell response
      generated by a variety of prophylactic and therapeutic vaccines designed to
      target a cellular response.

PMID- 24884567
TI  - Nasal application of neuropeptide S inhibits arthritis pain-related behaviors
      through an action in the amygdala.
AB  - Recently discovered neuropeptide S (NPS) has anxiolytic and pain-inhibiting
      effects in rodents. We showed previously that NPS increases synaptic inhibition
      of amygdala output to inhibit pain behaviors. The amygdala plays a key role in
      emotional-affective aspects of pain. Of clinical significance is that NPS can be
      applied nasally to exert anxiolytic effects in rodents. This study tested the
      novel hypothesis that nasal application of NPS can inhibit pain-related behaviors
      in an arthritis model through NPS receptors (NPSR) in the amygdala. Behaviors and
      electrophysiological activity of amygdala neurons were measured in adult male
      Sprague Dawley rats. Nasal application of NPS, but not saline, inhibited audible
      and ultrasonic vocalizations and had anxiolytic-like effects in the elevated plus
      maze test in arthritic rats (kaolin/carrageenan knee joint arthritis model) but
      had no effect in normal rats. Stereotaxic application of a selective non-peptide
      NPSR antagonist (SHA68) into the amygdala by microdialysis reversed the
      inhibitory effects of NPS. NPS had no effect on hindlimb withdrawal thresholds.
      We showed previously that intra-amygdala application of an NPSR antagonist alone
      had no effect. Nasal application of NPS or stereotaxic application of NPS into
      the amygdala by microdialysis inhibited background and evoked activity of
      amygdala neurons in arthritic, but not normal, anesthetized rats. The inhibitory
      effect was blocked by a selective NPSR antagonist ([D-Cys(tBu)5]NPS). In
      conclusion, nasal application of NPS can inhibit emotional-affective, but not
      sensory, pain-related behaviors through an action in the amygdala. The beneficial
      effects of non-invasive NPS application may suggest translational potential. 

PMID- 24884569
TI  - Framework of behavioral indicators for outcome evaluation of TB health promotion:
      a Delphi study of TB suspects and Tb patients.
AB  - BACKGROUND: Health promotion for prevention and control of Tuberculosis (TB) is
      implemented worldwide because of its importance, but few reports have evaluated
      its impact on behavior due to a lack of standard outcome indicators. The
      objective of this study was to establish a framework of behavioral indicators for
      outcome evaluation of TB health promotion among TB suspects and patients.
      METHODS: A two-round modified Delphi method involving sixteen TB control experts
      was used to establish a framework of behavioral indicators for outcome evaluation
      of TB health promotion targeted at TB suspects and patients. RESULTS: Sixteen of
      seventeen invited experts in TB control (authority score of 0.91 on a 1.0 scale)
      participated in round 1 survey. All sixteen experts also participated in a second
      round survey. After two rounds of surveys and several iterations among the
      experts, there was consensus on a framework of indicators for measuring outcomes
      of TB health promotion for TB suspects and patients. For TB suspects, the experts
      reached consensus on 2 domains ("Healthcare seeking behavior" and "Transmission
      prevention"), 3 subdomains ("Seeking care after onset of TB symptoms", "Pathways
      of seeking care" and "Interpersonal contact etiquette"), and 8 indicators
      (including among others, "Length of patient delay"). For TB patients, consensus
      was reached on 3 domains ("Adherence to treatment", "Healthy lifestyle" and
      "Transmission prevention"), 8 subdomains (including among others, "Adherence to
      their medication"), and 14 indicators (including "Percentage of patients who
      adhered to their medication"). Operational definitions and data sources were
      provided for each indicator. CONCLUSIONS: The findings of this study provide the
      basis for debate among international experts on a framework for achieving global
      consensus on outcome indicators for TB health promotion interventions targeted at
      TB patients and suspects. Such consensus will help to increase effectiveness of
      TB health promotion, while ensuring international comparability of outcome data.

PMID- 24884570
TI  - A systematic review and meta-analysis on the prevalence of dietary supplement use
      by military personnel.
AB  - BACKGROUND: Although a number of studies have been conducted on the prevalence of
      dietary supplement (DS) use in military personnel, these investigations have not
      been previously summarized. This article provides a systematic literature review
      of this topic. METHODS: Literature databases, reference lists, and other sources
      were searched to find studies that quantitatively examined the prevalence of DS
      use in uniformed military groups. Prevalence data were summarized by gender and
      military service. Where there were at least two investigations, meta-analysis was
      performed using a random model and homogeneity of the prevalence values was
      assessed. RESULTS: The prevalence of any DS use for Army, Navy, Air Force, and
      Marine Corps men was 55%, 60%, 60%, and 61%, respectively; for women
      corresponding values were 65%, 71%, 76%, and 71%, respectively. Prevalence of
      multivitamin and/or multimineral (MVM) use for Army, Navy, Air Force, and Marine
      Corps men was 32%, 46%, 47%, and 41%, respectively; for women corresponding
      values were 40%, 55%, 63%, and 53%, respectively. Use prevalence of any
      individual vitamin or mineral supplement for Army, Navy, Air Force, and Marine
      Corps men was 18%, 27%, 25%, and 24%, respectively; for women corresponding
      values were 29%, 36%, 40%, and 33%, respectively. Men in elite military groups
      (Navy Special Operations, Army Rangers, and Army Special Forces) had a use
      prevalence of 76% for any DS and 37% for MVM, although individual studies were
      not homogenous. Among Army men, Army women, and elite military men, use
      prevalence of Vitamin C was 15% for all three groups; for Vitamin E, use
      prevalence was 8%, 7%, and 9%, respectively; for sport drinks, use prevalence was
      22%, 25% and 39%, respectively. Use prevalence of herbal supplements was
      generally low compared to vitamins, minerals, and sport drinks, <=5% in most
      investigations. CONCLUSIONS: Compared to men, military women had a higher use
      prevalence of any DS and MVM. Army men and women tended to use DSs and MVM less
      than other service members. Elite military men appeared to use DSs and sport
      drinks more than other service members.

PMID- 24884571
TI  - Attenuated neuroprotective effect of riboflavin under UV-B irradiation via miR
      203/c-Jun signaling pathway in vivo and in vitro.
AB  - BACKGROUND: Riboflavin (RF) or vitamin B2 is known to have neuroprotective
      effects. In the present study, we report the attenuation of the neuroprotective
      effects of RF under UV-B irradiation. Preconditioning of UV-B irradiated
      riboflavin (UV-B-RF) showed attenuated neuroprotective effects compared to that
      of RF in SH-SY5Y neuroblostoma cell line and primary cortical neurons in vitro
      and a rat model of cerebral ischemia in vivo. RESULTS: Results indicated that RF
      pretreatment significantly inhibited cell death and reduced LDH secretion
      compared to that of the UV-B-RF pretreatment in primary cortical neuron cultures
      subjected to oxygen glucose deprivation in vitro and cortical brain tissue
      subjected to ischemic injury in vivo. Further mechanistic studies using cortical
      neuron cultures revealed that RF treatment induced increased miR-203 expression
      which in turn inhibited c-Jun expression and increased neuronal cell survival.
      Functional assays clearly demonstrated that the UV-B-RF preconditioning failed to
      sustain the increased expression of miR-203 and the decreased levels of c-Jun,
      mediating the neuroprotective effects of RF. UV-B irradiation attenuated the
      neuroprotective effects of RF through modulation of the miR-203/c-Jun signaling
      pathway. CONCLUSION: Thus, the ability of UV-B to serve as a modulator of this
      neuroprotective signaling pathway warrants further studies into its role as a
      regulator of other cytoprotective/neuroprotective signaling pathways.

PMID- 24884572
TI  - Molecular evolution accompanying functional divergence of duplicated genes along
      the plant starch biosynthesis pathway.
AB  - BACKGROUND: Starch is the main source of carbon storage in the Archaeplastida.
      The starch biosynthesis pathway (sbp) emerged from cytosolic glycogen metabolism
      shortly after plastid endosymbiosis and was redirected to the plastid stroma
      during the green lineage divergence. The SBP is a complex network of genes, most
      of which are members of large multigene families. While some gene duplications
      occurred in the Archaeplastida ancestor, most were generated during the sbp
      redirection process, and the remaining few paralogs were generated through
      compartmentalization or tissue specialization during the evolution of the land
      plants. In the present study, we tested models of duplicated gene evolution in
      order to understand the evolutionary forces that have led to the development of
      SBP in angiosperms. We combined phylogenetic analyses and tests on the rates of
      evolution along branches emerging from major duplication events in six gene
      families encoding sbp enzymes. RESULTS: We found evidence of positive selection
      along branches following cytosolic or plastidial specialization in two starch
      phosphorylases and identified numerous residues that exhibited changes in volume,
      polarity or charge. Starch synthases, branching and debranching enzymes
      functional specializations were also accompanied by accelerated evolution.
      However, none of the sites targeted by selection corresponded to known functional
      domains, catalytic or regulatory. Interestingly, among the 13 duplications
      tested, 7 exhibited evidence of positive selection in both branches emerging from
      the duplication, 2 in only one branch, and 4 in none of the branches.
      CONCLUSIONS: The majority of duplications were followed by accelerated evolution
      targeting specific residues along both branches. This pattern was consistent with
      the optimization of the two sub-functions originally fulfilled by the ancestral
      gene before duplication. Our results thereby provide strong support to the so
      called "Escape from Adaptive Conflict" (EAC) model. Because none of the residues
      targeted by selection occurred in characterized functional domains, we propose
      that enzyme specialization has occurred through subtle changes in affinity,
      activity or interaction with other enzymes in complex formation, while the basic
      function defined by the catalytic domain has been maintained.

PMID- 24884573
TI  - The interferon-inducible antiviral protein Daxx is not essential for interferon
      mediated protection against avian sarcoma virus.
AB  - BACKGROUND: The antiviral protein Daxx acts as a restriction factor of avian
      sarcoma virus (ASV; Retroviridae) in mammalian cells by promoting epigenetic
      silencing of integrated proviral DNA. Although Daxx is encoded by a type I
      (alpha/beta) interferon-stimulated gene, the requirement for Daxx in the
      interferon anti-retroviral response has not been elucidated. In this report, we
      describe the results of experiments designed to investigate the role of Daxx in
      the type I interferon-induced anti-ASV response. FINDINGS: Using an ASV reporter
      system, we show that type I interferons are potent inhibitors of ASV replication.
      We demonstrate that, while Daxx is necessary to silence ASV gene expression in
      the absence of interferons, type I interferons are fully-capable of inducing an
      antiviral state in the absence of Daxx. CONCLUSIONS: These results provide
      evidence that Daxx is not essential for the anti-ASV interferon response in
      mammalian cells, and that interferons deploy multiple, redundant antiviral
      mechanisms to protect cells from ASV.

PMID- 24884574
TI  - Fast food diet with CCl4 micro-dose induced hepatic-fibrosis--a novel animal
      model.
AB  - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is defined as a spectrum of
      conditions ranging from hepatocellular steatosis to steatohepatitis and fibrosis,
      progressing to cirrhosis, which occur in the absence of excessive alcohol use.
      Several animal models capture aspects of NAFLD but are limited either in their
      representation of the disease stages or use for development of therapeutics due
      to the extended periods of time required to develop full histological features.
      METHODS: Here, we report the development of a novel rat model for NAFLD that
      addresses some of these limitations. We used a fast food diet (FFD) and a CCl4
      micro dose (0.5 ml/kg B.wt) for 8 weeks in Wistar rats. Serological analyses,
      gene expression profiling and liver histology studies were conducted to
      investigate the development of steatosis, steatohepatitis and fibrosis in the FFD
      CCl4 model when compared to the individual effects of a FFD or a micro dose of
      CCl4 in rats. RESULTS: The serum biochemical profile of the FFD-CCl4 model showed
      an increase in liver injury and fibrosis. This was also accompanied by a
      significant increase in liver triglycerides (TG), inflammation and oxidative
      stress. Importantly, we observed extensive fibrosis confirmed by: i) increased
      gene expression of fibrosis markers and, ii) moderate to severe collagen
      deposition seen as perisinusoidal and bridging fibrosis using H&E, Trichome and
      Sirius Red staining. CONCLUSIONS: In summary, we find that the FFD-CCl4 rat model
      developed NAFLD histological features including, steatosis, inflammation and
      fibrosis in 8 weeks showing promise as a model that can be used to develop NAFLD
      therapeutics and liver anti-fibrotics.

PMID- 24884575
TI  - Dynamics of a combined Medea-underdominant population transformation system.
AB  - BACKGROUND: Transgenic constructs intended to be stably established at high
      frequencies in wild populations have been demonstrated to "drive" from low
      frequencies in experimental insect populations. Linking such population
      transformation constructs to genes which render them unable to transmit pathogens
      could eventually be used to stop the spread of vector-borne diseases like malaria
      and dengue. RESULTS: Generally, population transformation constructs with only a
      single transgenic drive mechanism have been envisioned. Using a theoretical
      modelling approach we describe the predicted properties of a construct combining
      autosomal Medea and underdominant population transformation systems. We show that
      when combined they can exhibit synergistic properties which in broad
      circumstances surpass those of the single systems. CONCLUSION: With combined
      systems, intentional population transformation and its reversal can be achieved
      readily. Combined constructs also enhance the capacity to geographically restrict
      transgenic constructs to targeted populations. It is anticipated that these
      properties are likely to be of particular value in attracting regulatory approval
      and public acceptance of this novel technology.

PMID- 24884577
TI  - Gerontology and youth-focused service learning: the relation between service
      recipient age and student responses.
AB  - Service learning is a pedagogical technique that integrates traditional
      coursework with activities outside the classroom that meet the needs of the
      community. Gerontology-focused service learning has been incorporated into many
      courses that cover aging content and is believed to be beneficial to the learning
      process. Other research has demonstrated that service learning in general has
      benefits, regardless of the age of the service recipient. It is unclear whether
      benefits associated with gerontology-focused service learning are unique to
      experiences with older adults or are a product of the general benefits associated
      with this pedagogy. This study examined student responses to gerontology-focused
      service learning compared to youth-focused service learning. The results revealed
      that students working with older adults reported more negative expectations
      related to the assignment, more positive experiences interacting with the service
      recipients, and more reports of learning benefits attributed to service learning.

PMID- 24884576
TI  - Cloning and expression of N22 region of Torque Teno virus (TTV) genome and use of
      peptide in developing immunoassay for TTV antibodies.
AB  - BACKGROUND: Torque Teno Virus (TTV) is a DNA virus with high rate of prevalence
      globally. Since its discovery in 1997, several studies have questioned the role
      of this virus in causing disease. However, it still remains an enigma. Although
      methods are available for detection of TTV infection, there is still a need for
      simple, rapid and reliable method for screening of this virus in human
      population. Present investigation describes the cloning and expression of N22
      region of TTV-genome and the use of expressed peptide in development of
      immunoassay to detect anti-TTV antibodies in serum. Since TTV genotype-1 is more
      common in India, the serum positive for genotype-1 was used as source of N22 for
      expression purpose. METHODS: Full length N22 region of ORF1 from TTV genotype-1
      was amplified and cloned in pGEM(r)-T Easy vector. After cloning, the amplicon
      was transformed and expressed as a fusion protein containing hexa-histidine tag
      in pET-28a(+) vector using BL21 E. coli cells as host. Expression was conducted
      both in LB medium as well as ZYP-5052 auto-induction medium. The expressed
      peptide was purified using metal-chelate affinity chromatography and used as
      antigen in developing a blot immunoassay. RESULTS: Analysis of translated product
      by SDS-PAGE and western blotting demonstrated the presence of 25 kDa polypeptide
      produced after expression. Solubility studies showed the polypeptide to be
      associated with insoluble fraction. The use of this peptide as antigen in blot
      assay produced prominent spot on membrane treated with sera from TTV-infected
      patients. Analysis of sera from 75 patients with liver and renal diseases
      demonstrated a successful implication of N22 polypeptide based immunoassay in
      screening sera for anti-TTV antibodies. Comparison of the immunoassay developed
      using expressed N22 peptide with established PCR method for TTV-DNA detection
      showed good coherence between TTV-DNA and presence of anti-TTV antibodies in the
      sera analysed. CONCLUSIONS: This concludes that TTV N22 region may be expressed
      and safely used as antigen for blot assay to detect anti-TTV antibodies in sera.

PMID- 24884578
TI  - A randomized Phase 2 trial of telavancin versus standard therapy in patients with
      uncomplicated Staphylococcus aureus bacteremia: the ASSURE study.
AB  - BACKGROUND: Staphylococcus aureus bacteremia is a common infection associated
      with significant morbidity and mortality. Telavancin is a bactericidal
      lipoglycopeptide active against Gram-positive pathogens, including methicillin
      resistant S. aureus (MRSA). We conducted a randomized, double-blind, Phase 2
      trial in patients with uncomplicated S. aureus bacteremia. METHODS: Patients were
      randomized to either telavancin or standard therapy (vancomycin or anti
      staphylococcal penicillin) for 14 days. Continuation criteria were set to avoid
      complicated S. aureus bacteremia. The primary end point was clinical cure at 84
      days. RESULTS: In total, 60 patients were randomized and 58 received >=1 study
      medication dose (all-treated), 31 patients fulfilled inclusion/exclusion and
      continuation criteria (all-treated target [ATT]) (telavancin 15, standard therapy
      16), and 17 patients were clinically evaluable (CE) (telavancin 8, standard
      therapy 9). Mean age (ATT) was 60 years. Intravenous catheters were the most
      common source of S. aureus bacteremia and ~50% of patients had MRSA. A similar
      proportion of CE patients were cured in the telavancin (88%) and standard therapy
      (89%) groups. All patients with MRSA bacteremia were cured and one patient with
      MSSA bacteremia failed study treatment in each group. Although adverse events
      (AEs) were more common in the telavancin ATT group (90% vs. 72%), AEs leading to
      drug discontinuation were similar (7%) in both treatment arms. Potentially
      clinically significant increases in serum creatinine (>=1.5 mg/dl and at least
      50% greater than baseline) were more common in the telavancin group (20% vs. 7%).
      CONCLUSIONS: This study suggests that telavancin may have utility for treatment
      of uncomplicated S. aureus bacteremia; additional studies are warranted.
      (Telavancin for Treatment of Uncomplicated Staphylococcus Aureus Bacteremia
      (ASSURE); NCT00062647).

PMID- 24884579
TI  - Does IQ influence associations between ADHD symptoms and other cognitive
      functions in young preschoolers?
AB  - BACKGROUND: Working memory, inhibition, and expressive language are often
      impaired in ADHD and many children with ADHD have lower IQ-scores than typically
      developing children. The aim of this study was to test whether IQ-score
      influences associations between ADHD symptoms and verbal and nonverbal working
      memory, inhibition, and expressive language, respectively, in a nonclinical
      sample of preschool children. METHODS: In all, 1181 children recruited from the
      Norwegian Mother and Child Cohort Study were clinically assessed at the age of 36
      to 46 months. IQ-score and working memory were assessed with subtasks from the
      Stanford Binet test battery, expressive language was reported by preschool
      teachers (Child Development Inventory), response inhibition was assessed with a
      subtask from the NEPSY test, and ADHD symptoms were assessed by parent interview
      (Preschool Age Psychiatric Assessment). RESULTS: The results showed an
      interaction between ADHD symptoms and IQ-score on teacher-reported expressive
      language. In children with below median IQ-score, a larger number of ADHD
      symptoms were more likely to be accompanied by reports of lower expressive
      language skills, while the level of ADHD symptoms exerted a smaller effect on
      reported language skills in children with above median IQ-score. The associations
      between ADHD symptoms and working memory and response inhibition, respectively,
      were not influenced by IQ-score. CONCLUSIONS: Level of IQ-score affected the
      relation between ADHD symptoms and teacher-reported expressive language, whereas
      associations between ADHD symptoms and working memory and response inhibition,
      respectively, were significant and of similar sizes regardless of IQ-score. Thus,
      in preschoolers, working memory and response inhibition should be considered
      during an ADHD assessment regardless of IQ-score, while language skills of young
      children are especially important to consider when IQ-scores are average or low.

PMID- 24884580
TI  - Whole body magnetic resonance angiography and computed tomography angiography in
      the vascular mapping of head and neck: an intraindividual comparison.
AB  - INTRODUCTION: The aim of the study was to compare the detectability of neck
      vessels with contrast enhanced magnetic resonance angiography (MRA) in the
      setting of a whole-body MRA and multislice computed tomography angiography (CTA)
      for preoperative vascular mapping of head and neck. METHODS: In 20 patients MRA
      was performed prior to microvascular reconstruction of the mandible with
      osteomyocutaneous flaps. CTA of the neck served as the method of reference.1.5 T
      contrast enhanced magnetic resonance angiograms were acquired to visualize the
      vascular structures of the neck in the setting of a whole-body MRA examination.
      64-slice spiral computed tomography was performed with a dual-phase protocol,
      using the arterial phase images for 3D CTA reconstruction. Maximum intensity
      projection was employed to visualize MRA and CTA data. To retrieve differences in
      the detectability of vessel branches between MRA and CTA, a McNemar test was
      performed. RESULTS: All angiograms were of diagnostic quality. There were no
      statistically significant differences between MRA and CTA for the detection of
      branches of the external carotid artery that are relevant host vessels for
      microsurgery (p = 0.118). CTA was superior to MRA if all the external carotid
      artery branches were included (p < 0.001). CONCLUSIONS: MRA is a reliable
      alternative to CTA in vascular mapping of the cervical vasculature for planning
      of microvascular reconstruction of the mandible. In the setting of whole-body MRA
      it could serve as a radiation free one-stop-shop tool for preoperative assessment
      of the arterial system, potentially covering both, the donor and host site in one
      single examination.

PMID- 24884581
TI  - A systematic review for pursuing the presence of antibiotic associated
      enterocolitis caused by methicillin resistant Staphylococcus aureus.
AB  - BACKGROUND: Although it has received a degree of notoriety as a cause for
      antibiotic-associated enterocolitis (AAE), the role of methicillin resistant
      Staphylococcus aureus (MRSA) in the pathogenesis of this disease remains
      enigmatic despite a multitude of efforts, and previous studies have failed to
      conclude whether MRSA can cause AAE. Numerous cases of AAE caused by MRSA have
      been reported from Japan; however, due to the fact that these reports were
      written in the Japanese language and a good portion lacked scientific rigor, many
      of these reports went unnoticed. METHODS: We conducted a systematic review of
      pertinent literatures to verify the existence of AAE caused by MRSA. We modified
      and applied methods in common use today and used a total of 9 criteria to prove
      the existence of AAE caused by Klebsiella oxytoca. MEDLINE/Pubmed, Excerpta
      Medica Database (EMBASE), the Cochrane Database of Systematic Reviews, and the
      Japan Medical Abstract Society database were searched for studies published prior
      to March 2013. RESULTS: A total of 1,999 articles were retrieved for evaluation.
      Forty-five case reports/series and 9 basic studies were reviewed in detail. We
      successfully identified articles reporting AAE with pathological and microscopic
      findings supporting MRSA as the etiological agent. We also found comparative
      studies involving the use of healthy subjects, and studies detecting probable
      toxins. In addition, we found animal models in which enteritis was induced by
      introducing MRSA from patients. Although we were unable to identify a single
      study that encompasses all of the defined criteria, we were able to fulfill all 9
      elements of the criteria by collectively analyzing multiple studies. CONCLUSIONS:
      AAE caused by MRSA-although likely to be rarer than previous Japanese literatures
      have suggested-most likely does exist.

PMID- 24884582
TI  - Characteristics of patients with acute traumatic brain injury discharged against
      medical advice in a level 1 urban trauma centre.
AB  - PRIMARY OBJECTIVE: To predict which characteristics are associated with patients
      at risk of discharge against medical advice (AMA). RESEARCH DESIGN: Data were
      retrospectively collected on individuals (n = 5642) admitted to the Traumatic
      Brain Injury Program of the MUHC-MGH. METHODS AND PROCEDURES: Outcome measures
      used were length of stay (LOS), the Extended Glasgow Outcome Scale (GOSE) as well
      as the Functional Independence Measure (FIM(r)). MAIN OUTCOMES: The overall rate
      of patients leaving AMA was 1.9% (n = 108). Age was negatively associated with
      AMA discharge (95% CI OR = [0.966;0.991]). Patients with a history of substance
      abuse were ~2-times more likely to leave AMA than those not using substances
      before injury (95% CI OR = [1.172;3.314]) and the homeless were ~3-times more
      likely to leave AMA compared to those who were not homeless (95% CI OR =
      [1.260;7.138]). Length of stay (LOS) was shorter for patients leaving AMA (p <
      0.001) and they showed better outcome (GOSE: p < 0.001; FIM: p = 0.032).
      CONCLUSIONS: Knowing the profile of patients with TBI leaving AMA hospitalized in
      an urban Level 1 Trauma centre will help in the development of effective
      strategies based on patient needs, values and pre-injury psychosocial situation
      to encourage them to complete their treatment course in hospital.

PMID- 24884583
TI  - Show what you know and deal with stress yourself: a qualitative interview study
      of medical interns' perceptions of stress and gender.
AB  - BACKGROUND: Medical students report high stress levels and in particular, the
      clinical phase is a demanding one. The field of medicine is still described as
      having a patriarchal culture which favors aspects like a physicians' perceived
      certainty and rationalism. Also, the Effort-Recovery Model explains stress as
      coming from a discrepancy between job demands, job control, and perceived work
      potential. Gendered differences in stress are reported, but not much is known
      about medical interns' perceptions of how gender plays in relation to stress. The
      aim of this study is to explore how medical interns experience and cope with
      stress, as well as how they reflect on the gendered aspects of stress. METHODS:
      In order to do this, we have performed a qualitative study. In 2010-2011, semi
      structured qualitative interviews were conducted with seventeen medical interns
      across all three years of the Masters programme (6 male, 11 female) at a Dutch
      medical school. The interview guide is based on gender theory, the Effort
      Recovery Model, and empirical literature. Transcribed interviews have been
      analyzed thematically. RESULTS: First, stress mainly evolves from having to prove
      one's self and show off competencies and motivation ("Show What You Know...").
      Second, interns seek own solutions for handling stress because it is not open for
      discussion (... "And Deal With Stress Yourself"). Patient encounters are a source
      of pride and satisfaction rather than a source of stress. But interns report
      having to present themselves as 'professional and self-confident', remaining
      silent about experiencing stress. Female students are perceived to have more
      stress and to study harder in order to live up to expectations. CONCLUSIONS: The
      implicit message interns hear is to remain silent about insecurities and stress,
      and, in particular, female students might face disadvantages. Students who feel
      less able to manifest the 'masculine protest' may benefit from a culture that
      embraces more collaborative styles, such as having open conversation about
      stress.

PMID- 24884584
TI  - Discriminative ability of the generic and condition specific Oral Impact on Daily
      Performance (OIDP) among adolescents with and without hypodontia.
AB  - BACKGROUND: The aims of this study were to (1) investigate to what extent the
      generic and condition specific (CS) forms of the oral impact of daily performance
      (OIDP) inventory discriminate between a group of patients with hypodontia and a
      group of patients having malocclusion, (2) assess the association of the generic
      and CS OIDP with severity and localisation of hypodontia, whilst adjusting for
      patients' age and sex. METHODS: A total of 163 patients aged 10-17 years were
      included in a cross-sectional study. Two groups were investigated: 62 patients
      with non-syndromic hypodontia and 101 non-hypodontia patients. Both groups had a
      malocclusion of similar treatment need. All patients underwent a clinical and
      radiographic examination and completed a Norwegian version of the generic and the
      CS OIDP inventory. CS scores were established for impacts attributed to
      hypodontia. RESULTS: The mean number of missing teeth in the hypodontia group was
      6.2. The prevalence of generic and CS oral impacts in the hypodontia group were
      64% and 30%, and the corresponding rates in the non-hypodontia group were 62% and
      10%. The generic OIDP did not discriminate between the two groups with respect to
      overall scores. The CS OIDP discriminated strongly between patients with and
      without hypodontia regarding problems with emotional status, showing teeth,
      social contact, speaking and carrying out work. Compared to the non-hypodontia
      group, patients with hypodontia, with severe hypodontia (>= 6 missing teeth) and
      upper anterior hypodontia were respectively 3.4, 2.5 and 7.0 times more likely to
      report any oral impact attributed to small teeth, gaps between teeth and missing
      teeth. CONCLUSIONS: Hypodontia and malocclusion patients report a considerable
      burden of oral impacts. The CS-OIDP measure discriminated most effectively
      between patients with and without hypodontia and was related to severity and
      upper anterior localisation of hypodontia.

PMID- 24884585
TI  - Optimization of the viability of stem cells derived from umbilical cord blood
      after maternal supplementation with DHA during the second or third trimester of
      pregnancy: study protocol for a randomized controlled trial.
AB  - BACKGROUND: Umbilical cord blood (UCB) is an important source of hematopoietic
      stem cells (HSCs). However, the concentration of cells in cord blood units is
      limited and this may represent the main restriction to their therapeutic clinical
      use. The percentage of metabolically active stem cells provides a measure of the
      viability of cells in an UCB sample. It follows that an active cellular
      metabolism causes a proliferation in stem cells, offering an opportunity to
      increase the cellular concentration. A high cell dose is essential when
      transplanting cord stem cells, guaranteeing, in the receiving patient, a
      successful outcome.This study is designed to evaluate the impact of
      docosahexaenoic acid (DHA) supplementation in pregnant women, in order to
      increase the quantity and viability of the cells in UCB samples. METHODS/DESIGN:
      The metabolic demand of DHA increases in the course of pregnancy and reaches
      maximum absorption during the third trimester of pregnancy. According to these
      observations, this trial will be divided into two different experimental groups:
      in the first group, participants will be enrolled from the 20th week of estimated
      stage of gestation, before the maximum absorption of DHA; while in the second
      group, enrolment will start from the 28th week of estimated stage of gestation,
      when the DHA request is higher. Participants in the trial will be divided and
      randomly assigned to the placebo group or to the experimental group. Each
      participant will receive a complete set of capsules of either placebo (250 mg of
      olive oil) or DHA (250 mg), to take one a day from the 20th or from the 28th
      week, up to the 40th week of estimated gestational age. Samples of venous blood
      will be taken from all participants before taking placebo or DHA, at the 20th or
      at the 28th week, and at the 37th to 38th week of pregnancy to monitor the level
      of DHA. Cell number and cellular viability will be evaluated by flow cytometry
      within 48 hours of the UCB sample collection. TRIAL REGISTRATION: International
      Standard Randomised Controlled Trial Number Register: ISRCTN58396079.
      Registration date: 8 October 2013.

PMID- 24884588
TI  - The clinical adoption meta-model: a temporal meta-model describing the clinical
      adoption of health information systems.
AB  - Health information systems (HISs) hold the promise to transform health care;
      however, their adoption is challenged. We have developed the Clinical Adoption
      Meta-Model (CAMM) to help describe processes and possible challenges with
      clinical adoption. The CAMM, developed through an action research study to
      evaluate a provincial HIS, is a temporal model with four dimensions:
      availability, use, behaviour changes, and outcome changes. Seven CAMM archetypes
      are described, illustrating classic trajectories of adoption of HISs over time.
      Each archetype includes an example from the literature. The CAMM and its
      archetypes can support HIS implementers, evaluators, learners, and researchers.

PMID- 24884587
TI  - Population genetic analysis of bi-allelic structural variants from low-coverage
      sequence data with an expectation-maximization algorithm.
AB  - BACKGROUND: Population genetics and association studies usually rely on a set of
      known variable sites that are then genotyped in subsequent samples, because it is
      easier to genotype than to discover the variation. This is also true for
      structural variation detected from sequence data. However, the genotypes at known
      variable sites can only be inferred with uncertainty from low coverage data.
      Thus, statistical approaches that infer genotype likelihoods, test hypotheses,
      and estimate population parameters without requiring accurate genotypes are
      becoming popular. Unfortunately, the current implementations of these methods are
      intended to analyse only single nucleotide and short indel variation, and they
      usually assume that the two alleles in a heterozygous individual are sampled with
      equal probability. This is generally false for structural variants detected with
      paired ends or split reads. Therefore, the population genetics of structural
      variants cannot be studied, unless a painstaking and potentially biased
      genotyping is performed first. RESULTS: We present svgem, an expectation
      maximization implementation to estimate allele and genotype frequencies,
      calculate genotype posterior probabilities, and test for Hardy-Weinberg
      equilibrium and for population differences, from the numbers of times the alleles
      are observed in each individual. Although applicable to single nucleotide
      variation, it aims at bi-allelic structural variation of any type, observed by
      either split reads or paired ends, with arbitrarily high allele sampling bias. We
      test svgem with simulated and real data from the 1000 Genomes Project.
      CONCLUSIONS: svgem makes it possible to use low-coverage sequencing data to study
      the population distribution of structural variants without having to know their
      genotypes. Furthermore, this advance allows the combined analysis of structural
      and nucleotide variation within the same genotype-free statistical framework,
      thus preventing biases introduced by genotype imputation.

PMID- 24884589
TI  - Higher anti-depressant dose and major adverse outcomes in moderate chronic kidney
      disease: a retrospective population-based study.
AB  - BACKGROUND: Many older patients have chronic kidney disease (CKD), and a lower
      dose of anti-depressants paroxetine, mirtazapine and venlafaxine is recommended
      in patients with CKD to prevent drug accumulation from reduced elimination. Using
      information available in large population-based healthcare administrative
      databases, we conducted this study to determine if ignoring the recommendation
      and prescribing a higher versus lower dose of anti-depressants associates with a
      higher risk of adverse events. METHODS: We conducted a population-based cohort
      study to describe the 30-day risk of delirium in older adults who initiated a
      higher vs. lower dose of these three anti-depressants in routine care. We defined
      delirium using the best proxy available in our data sources - hospitalization
      with an urgent head computed tomography (CT) scan. We determined if CKD status
      modified the association between anti-depressant dose and outcome, and examined
      the secondary outcome of 30 day all-cause mortality. We used multivariable
      logistic regression analyses to estimate adjusted odds ratios (relative risk
      (RR)) and 95% confidence intervals. RESULTS: We identified adults (mean age 75)
      in Ontario who started a new study anti-depressant at a higher dose (n=36,651;
      31%) or lower dose (n=81,160; 69%). Initiating a higher vs. lower dose was not
      associated with an increased risk of hospitalization with head CT (1.09% vs.
      1.27% (adjusted RR 0.90; 95% CI, 0.80 to 1.02), but was associated with a lower
      risk of all-cause mortality (0.76% vs. 0.97% RR 0.82; 95% CI, 0.71 to 0.95).
      Neither of these relative risks were modified by the presence of CKD (p=0.16,
      0.68, respectively). CONCLUSIONS: We did not observe an increase in two adverse
      outcomes when study anti-depressants were initiated at a higher dose in elderly
      patients with moderate CKD. Contrary to our hypothesis, the 30-day risk of
      mortality was lower when a higher versus lower dose of anti-depressant was
      initiated in these patients, a finding which requires corroboration and further
      study.

PMID- 24884590
TI  - Discovery of the first potent and orally available agonist of the orphan G
      protein-coupled receptor 52.
AB  - G-protein-coupled receptor 52 (GPR52) is an orphan Gs-coupled G-protein-coupled
      receptor. GPR52 inhibits dopamine D2 receptor signaling and activates dopamine
      D1/N-methyl-d-aspartate receptors via intracellular cAMP accumulation, and
      therefore, GPR52 agonists may have potential as a novel class of antipsychotics.
      A series of GPR52 agonists with a bicyclic core was designed to fix the
      conformation of the phenethyl ether moiety of compounds 2a and 2b. 3-[2-(3-Chloro
      5-fluorobenzyl)-1-benzothiophen-7-yl]-N-(2-methoxyethyl)benzamide 7m showed
      potent activity (pEC50 = 7.53 +/- 0.08) and good pharmacokinetic properties.
      Compound 7m significantly suppressed methamphetamine-induced hyperactivity in
      mice after oral administration of 3 mg/kg without disturbance of motor function.

PMID- 24884591
TI  - Changing cluster composition in cluster randomised controlled trials: design and
      analysis considerations.
AB  - BACKGROUND: There are many methodological challenges in the conduct and analysis
      of cluster randomised controlled trials, but one that has received little
      attention is that of post-randomisation changes to cluster composition. To
      illustrate this, we focus on the issue of cluster merging, considering the impact
      on the design, analysis and interpretation of trial outcomes. METHODS: We
      explored the effects of merging clusters on study power using standard methods of
      power calculation. We assessed the potential impacts on study findings of both
      homogeneous cluster merges (involving clusters randomised to the same arm of a
      trial) and heterogeneous merges (involving clusters randomised to different arms
      of a trial) by simulation. To determine the impact on bias and precision of
      treatment effect estimates, we applied standard methods of analysis to different
      populations under analysis. RESULTS: Cluster merging produced a systematic
      reduction in study power. This effect depended on the number of merges and was
      most pronounced when variability in cluster size was at its greatest. Simulations
      demonstrate that the impact on analysis was minimal when cluster merges were
      homogeneous, with impact on study power being balanced by a change in observed
      intracluster correlation coefficient (ICC). We found a decrease in study power
      when cluster merges were heterogeneous, and the estimate of treatment effect was
      attenuated. CONCLUSIONS: Examples of cluster merges found in previously published
      reports of cluster randomised trials were typically homogeneous rather than
      heterogeneous. Simulations demonstrated that trial findings in such cases would
      be unbiased. However, simulations also showed that any heterogeneous cluster
      merges would introduce bias that would be hard to quantify, as well as having
      negative impacts on the precision of estimates obtained. Further methodological
      development is warranted to better determine how to analyse such trials
      appropriately. Interim recommendations include avoidance of cluster merges where
      possible, discontinuation of clusters following heterogeneous merges, allowance
      for potential loss of clusters and additional variability in cluster size in the
      original sample size calculation, and use of appropriate ICC estimates that
      reflect cluster size.

PMID- 24884592
TI  - The fecal microbiota of semi-free-ranging wood bison (Bison bison athabascae).
AB  - BACKGROUND: The intestinal tract harbours a complex and diverse microbial
      population that is important for health, yet has been poorly described in many
      species. This study explored the fecal microbiota of semi-free-ranging Wood bison
      (Bison bison athabascae). RESULTS: A total of 2081936 16S rRNA (V4) sequences
      from 40 bison were evaluated. CatchAll analysis of richness predicted a mean of
      10685 species per sample (range 5428-24764, SD 4136). Diversity was high, with an
      average inverse Simpson's index of 31.78 (SD 15.3, range 8.55-86.7). Twenty-one
      different phyla were identified; however, only Firmicutes and Proteobacteria,
      Actinobacteria accounted for >1% of sequences. Two distinct population clusters
      (Group A, n = 19 and Group B, n = 21) were evident based on both community
      membership and population structure. Group A had a significantly lower relative
      abundance of Actinobacteria (6.4 vs 11.8%, P = 0.002), Chloroflexi (0.002 vs
      0.013%, P = 0.014), Gemmatimonadetes (0.007 vs 0.15%, P = 0.038) and
      Proteobacteria (18.7 vs 42.5%, P = <0.0001) and a greater relative abundance of
      Firmicutes (70.9 vs 39.3%, P < 0.0001) than Group B. Within Group B,
      Alphaproteobacteria was the most common class of Proteobacteria (28% of all
      sequences), while Caulobacteraceae (18.5%), Pseudomonadaceae (3.5%),
      Hyphomicrobiaceae (3.5%), Alcaligenaceae (3.1%) and Xanthomonadaceae (2.6%) were
      the most abundant families. The twenty (3.1%) most abundant genera accounted for
      71% of sequences. No operational taxon units (OTUs) were found in all samples at
      a relative abundance of 1% or greater. One OTU (Clostridium cluster XI) was
      present at 1% or more in all Group A samples, with two other Clostridium cluster
      XI OTUs in 18/19 (95%) samples. No OTUs were found at that abundance in all Group
      B sample, but an unclassified Lachnospiraceae was present in 20/21 (95%) and
      Clostridium cluster XI and Brevundimonas were found in 19 (90%) samples.
      CONCLUSIONS: The fecal microbiota of Wood bison is rich and diverse. The presence
      of two distinct populations not associated with housing, age or gender suggest
      that enterotypes, distinctly different microbial population compositions that can
      achieve the same ultimate function, might be present in bison, as has been
      suggested in humans.

PMID- 24884593
TI  - XSAnno: a framework for building ortholog models in cross-species transcriptome
      comparisons.
AB  - BACKGROUND: The accurate characterization of RNA transcripts and expression
      levels across species is critical for understanding transcriptome evolution. As
      available RNA-seq data accumulate rapidly, there is a great demand for tools that
      build gene annotations for cross-species RNA-seq analysis. However, prevailing
      methods of ortholog annotation for RNA-seq analysis between closely-related
      species do not take inter-species variation in mappability into consideration.
      RESULTS: Here we present XSAnno, a computational framework that integrates
      previous approaches with multiple filters to improve the accuracy of inter
      species transcriptome comparisons. The implementation of this approach in
      comparing RNA-seq data of human, chimpanzee, and rhesus macaque brain
      transcriptomes has reduced the false discovery of differentially expressed genes,
      while maintaining a low false negative rate. CONCLUSION: The present study
      demonstrates the utility of the XSAnno pipeline in building ortholog annotations
      and improving the accuracy of cross-species transcriptome comparisons.

PMID- 24884594
TI  - The Welsh study of mothers and babies: protocol for a population-based cohort
      study to investigate the clinical significance of defined ultrasound findings of
      uncertain significance.
AB  - BACKGROUND: Improvement in ultrasound imaging has led to the identification of
      subtle non-structural markers during the 18 - 20 week fetal anomaly scan, such as
      echogenic bowel, mild cerebral ventriculomegaly, renal pelvicalyceal dilatation,
      and nuchal thickening. These markers are estimated to occur in between 0.6% and
      4.3% of pregnancies. Their clinical significance, for pregnancy outcomes or
      childhood morbidity, is largely unknown. The aim of this study is to estimate the
      prevalence of seven markers in the general obstetric population and establish a
      cohort of children for longer terms follow-up to assess the clinical significance
      of these markers. METHODS/DESIGN: All women receiving antenatal care within six
      of seven Welsh Health Boards who had an 18 to 20 week ultrasound scan in Welsh
      NHS Trusts between July 2008 and March 2011 were eligible for inclusion. Data
      were collected on seven markers (echogenic bowel, cerebral ventriculomegaly,
      renal pelvicalyceal dilatation, nuchal thickening, cardiac echogenic foci,
      choroid plexus cysts, and short femur) at the time of 18 - 20 week fetal anomaly
      scan. Ultrasound records were linked to routinely collected data on pregnancy
      outcomes (work completed during 2012 and 2013). Images were stored and reviewed
      by an expert panel.The prevalence of each marker (reported and validated) will be
      estimated. A projected sample size of 23,000 will allow the prevalence of each
      marker to be estimated with the following precision: a marker with 0.50%
      prevalence to within 0.10%; a marker with 1.00% prevalence to within 0.13%; and a
      marker with 4.50% prevalence to within 0.27%. The relative risk of major
      congenital abnormalities, stillbirths, pre-term birth and small for gestational
      age, given the presence of a validated marker, will be reported. DISCUSSION: This
      is a large, prospective study designed to estimate the prevalence of markers in a
      population-based cohort of pregnant women and to investigate associations with
      adverse pregnancy outcomes. The study will also establish a cohort of children
      that can be followed-up to explore associations between specific markers and
      longer-term health and social outcomes.

PMID- 24884596
TI  - Women's expectations and experiences of hormone treatment for sexual dysfunction.
AB  - OBJECTIVES: There is a paucity of information regarding women's expectations of
      medical treatment for female sexual dysfunction (FSD) and their self-appraisal of
      treatment outcomes. The aims of this study were to explore women's perception and
      expectations of treatment and their experiences of treatment for FSD using a
      qualitative approach. METHODS: First-time attendees to an endocrinologist with
      the complaint of sexual difficulties were identified and were invited to take
      part in an in-depth interview on the same day as, but prior to, their medical
      consultation. Follow-up phone interview took place 3-4 months later. RESULTS:
      Seventeen women, aged 26-70 years, participated in the face-to-face interview.
      Ten of these participated in the follow-up interview. Four major themes emerged
      from the women's narrative stories: (1) personal psychological distress
      associated with FSD, (2) concern about the adverse effect of FSD on the
      relationship with their sexual partner, (3) a belief in a relationship between
      FSD and 'hormone deficiency', and (4) an expectation of treatment, which included
      positive physical and sexual changes. CONCLUSIONS: Health professionals should be
      aware of the high degree of psychological distress that can result from FSD and
      consider available treatment options, which may include hormone therapy.

PMID- 24884595
TI  - Genome based analysis of type-I polyketide synthase and nonribosomal peptide
      synthetase gene clusters in seven strains of five representative Nocardia
      species.
AB  - BACKGROUND: Actinobacteria of the genus Nocardia usually live in soil or water
      and play saprophytic roles, but they also opportunistically infect the
      respiratory system, skin, and other organs of humans and animals. Primarily
      because of the clinical importance of the strains, some Nocardia genomes have
      been sequenced, and genome sequences have accumulated. Genome sizes of Nocardia
      strains are similar to those of Streptomyces strains, the producers of most
      antibiotics. In the present work, we compared secondary metabolite biosynthesis
      gene clusters of type-I polyketide synthase (PKS-I) and nonribosomal peptide
      synthetase (NRPS) among genomes of representative Nocardia species/strains based
      on domain organization and amino acid sequence homology. RESULTS: Draft genome
      sequences of Nocardia asteroides NBRC 15531(T), Nocardia otitidiscaviarum IFM
      11049, Nocardia brasiliensis NBRC 14402(T), and N. brasiliensis IFM 10847 were
      read and compared with published complete genome sequences of Nocardia farcinica
      IFM 10152, Nocardia cyriacigeorgica GUH-2, and N. brasiliensis HUJEG-1. Genome
      sizes are as follows: N. farcinica, 6.0 Mb; N. cyriacigeorgica, 6.2 Mb; N.
      asteroides, 7.0 Mb; N. otitidiscaviarum, 7.8 Mb; and N. brasiliensis, 8.9 - 9.4
      Mb. Predicted numbers of PKS-I, NRPS, and PKS-I/NRPS hybrid clusters ranged
      between 4-11, 7-13, and 1-6, respectively, depending on strains, and tended to
      increase with increasing genome size. Domain and module structures of
      representative or unique clusters are discussed in the text. CONCLUSION: We
      conclude the following: 1) genomes of Nocardia strains carry as many PKS-I and
      NRPS gene clusters as those of Streptomyces strains, 2) the number of PKS-I and
      NRPS gene clusters in Nocardia strains varies substantially depending on species,
      and N. brasiliensis strains carry the largest numbers of clusters among the
      species studied, 3) the seven Nocardia strains studied in the present work have
      seven common PKS-I and/or NRPS clusters, some of whose products are yet to be
      studied, and 4) different N. brasiliensis strains have some different gene
      clusters of PKS-I/NRPS, although the rest of the clusters are common within the
      N. brasiliensis strains. Genome sequencing suggested that Nocardia strains are
      highly promising resources in the search of novel secondary metabolites.

PMID- 24884597
TI  - Intelligent Structured Intermittent Auscultation (ISIA): evaluation of a decision
      making framework for fetal heart monitoring of low-risk women.
AB  - BACKGROUND: Research-informed fetal monitoring guidelines recommend intermittent
      auscultation (IA) for fetal heart monitoring for low-risk women. However, the use
      of cardiotocography (CTG) continues to dominate many institutional maternity
      settings. METHODS: A mixed methods intervention study with before and after
      measurement was undertaken in one secondary level health service to facilitate
      the implementation of an initiative to encourage the use of IA. The intervention
      initiative was a decision-making framework called Intelligent Structured
      Intermittent Auscultation (ISIA) introduced through an education session.
      RESULTS: Following the intervention, medical records review revealed an increase
      in the use of IA during labour represented by a relative change of 12%, with
      improved documentation of clinical findings from assessments, and a significant
      reduction in the risk of receiving an admission CTG (RR 0.75, 95% CI, 0.60-0.95,
      p = 0.016). CONCLUSION: The ISIA informed decision-making framework transformed
      the practice of IA and provided a mechanism for knowledge translation that
      enabled midwives to implement evidence-based fetal heart monitoring for low risk
      women.

PMID- 24884598
TI  - Which need characteristics influence healthcare service utilization in home care
      arrangements in Germany?
AB  - BACKGROUND: We see a growing number of older adults receiving long-term care in
      industrialized countries. The Healthcare Utilization Model by Andersen suggests
      that individual need characteristics influence utilization. The purpose of this
      study is to analyze correlations between need characteristics and service
      utilization in home care arrangements. METHODS: 1,152 respondents answered the
      questionnaire regarding their integration of services in their current and future
      care arrangements. Care recipients with high long-term care needs answered the
      questionnaire on their own, the family caregiver assisted the care recipient in
      answering the questions, or the family caregiver responded to the questionnaire
      on behalf of the care recipient. They were asked to rank specific needs according
      to their situation. We used descriptive statistics and regression analysis.
      RESULTS: Respondents are widely informed about services. Nursing services and
      counseling are the most used services. Short-term care and guidance and training
      have a high potential for future use. Day care, self-help groups, and mobile
      services were the most frequently rejected services in our survey. Women use more
      services than men and with rising age utilization increases. Long waiting times
      and bad health of the primary caregiver increases the chance of integrating
      services into the home care arrangements. CONCLUSION: The primary family
      caregiver has a high impact on service utilization. This indicates that the whole
      family should be approached when offering services. Professionals should react
      upon the specific needs of care dependents and their families.

PMID- 24884599
TI  - Paternal therapy with disease modifying drugs in multiple sclerosis and pregnancy
      outcomes: a prospective observational multicentric study.
AB  - BACKGROUND: Most of Multiple Sclerosis (MS) patients undergo disease modifying
      drug (DMD) therapy at childbearing age. The objective of this prospective,
      collaborative study, was to assess outcomes of pregnancies fathered by MS
      patients undergoing DMD. METHODS: Structured interviews on pregnancies fathered
      by MS patients gathered in the Italian Pregnancy Dataset were collected;
      pregnancies were divided according to father exposure or unexposure to DMD at
      time of procreation. Treatment were compared with multivariable logistic and
      linear models. RESULTS: Seventy-eight pregnancies fathered by MS patients were
      tracked. Forty-five patients were taking DMD at time of conception (39 beta
      interferons, 6 glatiramer acetate), while 33 pregnancies were unexposed to DMD.
      Seventy-five pregnancies ended in live-births, 44 in the exposed and 31 in the
      unexposed group. No significant differences between the two groups were found in
      the risk of spontaneous abortion or malformations (p > 0.454), mean gestational
      age (p = 0.513), frequency of cesarean delivery (p = 0.644), birth weight (p =
      0.821) and birth length (p = 0.649). In comparison with data of the Italian
      general population, the proportion of spontaneous abortion and caesarean delivery
      in exposed pregnancies fell within the estimates, while the proportion of pre
      term delivery in the exposed group was higher than expected. CONCLUSIONS: Our
      data indicate no association between paternal DMD exposure at time of conception
      and risk of spontaneous abortion, adverse fetal outcomes and congenital
      malformations. Further studies clarifying the role of DMD fathers intake prior
      and during pregnancy are desirable, to supply guidelines for clinical practice.

PMID- 24884600
TI  - Ion mobility spectrometry, infrared dissociation spectroscopy, and ab initio
      computations toward structural characterization of the deprotonated leucine
      enkephalin peptide anion in the gas phase.
AB  - Although the sequencing of protonated proteins and peptides with tandem mass
      spectrometry has blossomed into a powerful means of characterizing the proteome,
      much less effort has been directed at their deprotonated analogues, which can
      offer complementary sequence information. We present a unified approach to
      characterize the structure and intermolecular interactions present in the gas
      phase pentapeptide leucine-enkephalin anion by several vibrational spectroscopy
      schemes as well as by ion-mobility spectrometry, all of which are analyzed with
      the help of quantum-chemical computations. The picture emerging from this study
      is that deprotonation takes place at the C terminus. In this configuration, the
      excess charge is stabilized by strong intramolecular hydrogen bonds to two
      backbone amide groups and thus provides a detailed picture of a potentially
      common charge accommodation motif in peptide anions. 

PMID- 24884601
TI  - Smoking increases rectal cancer risk to the same extent in women as in men:
      results from a Norwegian cohort study.
AB  - BACKGROUND: Smoking has recently been established as a risk factor for rectal
      cancer. We examined whether the smoking-related increase in rectal cancer
      differed by gender. METHODS: We followed 602,242 participants (49% men), aged 19
      to 67 years at enrollment from four Norwegian health surveys carried out between
      1972 and 2003, by linkage to Norwegian national registries through December 2007.
      Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by fitting
      Cox proportional hazard models and adjusting for relevant confounders.
      Heterogeneity by gender in the effect of smoking and risk of rectal cancer was
      tested with Wald chi2. RESULTS: During a mean follow-up of 14 years, 1,336 men
      and 840 women developed invasive rectal cancer. Ever smokers had a significantly
      increased risk of rectal cancer of more than 25% for both men (HR = 1.27, 95% CI
      = 1.11-1.45) and women (HR = 1.28, 95% CI = 1.11-1.48) compared with gender
      specific never smokers. Men smoking >=20 pack-years had a significantly increased
      risk of rectal cancer of 35% (HR = 1.35, 95% CI = 1.14-1.58), whereas for women,
      it was 47% (HR = 1.47, 95% CI = 1.13-1.91) compared with gender-specific never
      smokers. For both men and women, we observed significant dose-response
      associations between the risk of rectal cancer for four variables [Age at smoking
      initiation in years (both ptrend <0.05), number of cigarettes smoked per day
      (both ptrend <0.0001), smoking duration in years (ptrend <0.05, <0.0001) and
      number of pack-years smoked (both ptrend <0.0001)]. The test for heterogeneity by
      gender was not significant between smoking status and the risk of rectal cancer
      (Wald chi2, p -value; current smokers = 0.85; former smokers = 0.87; ever smokers
      = 1.00). CONCLUSIONS: Smoking increases the risk of rectal cancer to the same
      extent in women as in men.

PMID- 24884602
TI  - Safety and tolerability of canakinumab, an IL-1beta inhibitor, in type 2 diabetes
      mellitus patients: a pooled analysis of three randomised double-blind studies.
AB  - BACKGROUND: We aimed to assess the safety and tolerability of different doses of
      canakinumab versus placebo in patients with type 2 diabetes mellitus (T2DM).
      METHODS: Data were pooled from three studies in 1026 T2DM patients with different
      routes of administration, treatment regimens and follow-up duration. Canakinumab
      groups were categorised as low (0.03 mg/kg i.v. once; N = 20), intermediate (0.1
      and 0.3 mg/kg i.v. once, 5 and 15 mg s.c. monthly; N = 247), medium (1.5 mg/kg
      i.v. once, 50 mg s.c. monthly and 150 mg s.c. once; N = 268), and high doses (10
      mg/kg i.v. once and 150 mg s.c. monthly; N = 137) and compared with placebo (N =
      354). Incidences of adverse events (AEs), serious AEs (SAEs), discontinuations
      due to AEs, deaths, AEs of special interest related to interleukin-1beta
      inhibition and T2DM disease, and laboratory abnormalities related to haematology
      and biochemistry parameters were reported. Safety was also analysed by age (<65,
      >=65) and gender. RESULTS: Average exposure across all groups was ~ 6 months
      (maximum ~17 months). No dose response in AEs was observed but a trend towards
      more patients having at least one AE across canakinumab groups relative to
      placebo (P = 0.0152) was observed. SAEs were few and the incidence rate for most
      canakinumab groups was lower than that of placebo group except for the high-dose
      group (0.94% versus 0.58% per month in placebo). A total of five patients
      discontinued treatment due to AEs across treatment groups. No death was reported
      in any of the three studies. A small, non-significant increase in the incidence
      rate of infection AEs was observed on canakinumab groups relative to placebo.
      Canakinumab was associated with mostly mild decreases in WBC, neutrophils and
      platelet counts. Additionally, mild increases in SGPT, SGOT and bilirubin were
      reported. Overall, despite small differences, no clinically relevant findings
      were observed with respect to laboratory values and vital signs. CONCLUSIONS:
      This pooled analysis demonstrated that canakinumab was safe and well tolerated
      over a treatment period up to 1.4 years at the four pooled doses evaluated, in
      agreement with safety findings reported in the individual studies.

PMID- 24884603
TI  - Accessibility and implementation in UK services of an effective depression
      relapse prevention programme - mindfulness-based cognitive therapy (MBCT): ASPIRE
      study protocol.
AB  - BACKGROUND: Mindfulness-based cognitive therapy (MBCT) is a cost-effective
      psychosocial prevention programme that helps people with recurrent depression
      stay well in the long term. It was singled out in the 2009 National Institute for
      Health and Clinical Excellence (NICE) Depression Guideline as a key priority for
      implementation. Despite good evidence and guideline recommendations, its roll-out
      and accessibility across the UK appears to be limited and inequitably
      distributed. The study aims to describe the current state of MBCT accessibility
      and implementation across the UK, develop an explanatory framework of what is
      hindering and facilitating its progress in different areas, and develop an
      Implementation Plan and related resources to promote better and more equitable
      availability and use of MBCT within the UK National Health Service.
      METHODS/DESIGN: This project is a two-phase qualitative, exploratory and
      explanatory research study, using an interview survey and in-depth case studies
      theoretically underpinned by the Promoting Action on Implementation in Health
      Services (PARIHS) framework. Interviews will be conducted with stakeholders
      involved in commissioning, managing and implementing MBCT services in each of the
      four UK countries, and will include areas where MBCT services are being
      implemented successfully and where implementation is not working well. In-depth
      case studies will be undertaken on a range of MBCT services to develop a detailed
      understanding of the barriers and facilitators to implementation. Guided by the
      study's conceptual framework, data will be synthesized across Phase 1 and Phase 2
      to develop a fit for purpose implementation plan. DISCUSSION: Promoting the
      uptake of evidence-based treatments into routine practice and understanding what
      influences these processes has the potential to support the adoption and spread
      of nationally recommended interventions like MBCT. This study could inform a
      larger scale implementation trial and feed into future implementation of MBCT
      with other long-term conditions and associated co-morbidities. It could also
      inform the implementation of interventions that are acceptable and effective, but
      are not widely accessible or implemented.

PMID- 24884604
TI  - Peripheral blood lymphocyte/monocyte ratio at the time of first relapse predicts
      outcome for patients with relapsed or primary refractory diffuse large B-cell
      lymphoma.
AB  - BACKGROUND: Despite the use of modern immunochemotherapy regimens, a significant
      proportion of diffuse large B-cell lymphoma (DLBCL) patients will relapse. We
      proposed absolute lymphocyte count/absolute monocyte count ratio (ALC/AMC ratio)
      as a new prognostic factor in relapsed or primary refractory DLBCL. METHODS: We
      retrospectively analyzed 163 patients who have been diagnosed with relapsed or
      primary refractory DLBCL. The overall survival (OS) and progression-free survival
      (PFS) were measured from the time of first relapse. The Cox proportional hazards
      model was used to evaluate ALC/AMC ratio as prognostic factors for OS and PFS.
      RESULTS: On univariate and multivariate analysis performed with factors included
      in the saaIPI, early relapse, prior exposure to rituximab and autologous stem
      cell transplantation (ASCT), the ALC/AMC ratio at the time of first relapse
      remained an independent predictor of PFS and OS (PFS: P < 0.001; OS: P < 0.001).
      Patients with lower ALC/AMC ratio (<2.0) had lower overall response rate, 1-year
      PFS and 2-year OS rate compared with those with higher ALC/AMC ratio (>=2.0).
      Moreover, the ALC/AMC ratio can provide additional prognostic information when
      superimposed on the saaIPI. CONCLUSIONS: Lower ALC/AMC ratio at the time of first
      relapse is a adverse prognostic factor for OS and PFS in relapsed or primary
      refractory DLBCL, and leads to the identification of high-risk patients otherwise
      classified as low/intermediate risk by the saaIPI alone.

PMID- 24884605
TI  - Predicting red blood cell transfusion in hospitalized patients: role of
      hemoglobin level, comorbidities, and illness severity.
AB  - BACKGROUND: Randomized controlled trial evidence supports a restrictive strategy
      of red blood cell (RBC) transfusion, but significant variation in clinical
      transfusion practice persists. Patient characteristics other than hemoglobin
      levels may influence the decision to transfuse RBCs and explain some of this
      variation. Our objective was to evaluate the role of patient comorbidities and
      severity of illness in predicting inpatient red blood cell transfusion events.
      METHODS: We developed a predictive model of inpatient RBC transfusion using
      comprehensive electronic medical record (EMR) data from 21 hospitals over a four
      year period (2008-2011). Using a retrospective cohort study design, we modeled
      predictors of transfusion events within 24 hours of hospital admission and
      throughout the entire hospitalization. Model predictors included administrative
      data (age, sex, comorbid conditions, admission type, and admission diagnosis),
      admission hemoglobin, severity of illness, prior inpatient RBC transfusion,
      admission ward, and hospital. RESULTS: The study cohort included 275,874 patients
      who experienced 444,969 hospitalizations. The 24 hour and overall inpatient RBC
      transfusion rates were 7.2% and 13.9%, respectively. A predictive model for
      transfusion within 24 hours of hospital admission had a C-statistic of 0.928 and
      pseudo-R2 of 0.542; corresponding values for the model examining transfusion
      through the entire hospitalization were 0.872 and 0.437. Inclusion of the
      admission hemoglobin resulted in the greatest improvement in model performance
      relative to patient comorbidities and severity of illness. CONCLUSIONS: Data from
      electronic medical records at the time of admission predicts with very high
      likelihood the incidence of red blood transfusion events in the first 24 hours
      and throughout hospitalization. Patient comorbidities and severity of illness on
      admission play a small role in predicting the likelihood of RBC transfusion
      relative to the admission hemoglobin.

PMID- 24884606
TI  - Comparison of Giemsa microscopy with nested PCR for the diagnosis of malaria in
      North Gondar, north-west Ethiopia.
AB  - BACKGROUND: Malaria remains one of the leading communicable diseases in Ethiopia.
      Early diagnosis combined with prompt treatment is one of the main strategies for
      malaria prevention and control. Despite its limitation, Giemsa microscopy is
      still considered to be the gold standard for malaria diagnosis. This study aimed
      to compare the performance of Giemsa microscopy with nested polymerase chain
      reaction (nPCR) for the diagnosis of malaria in north-west Ethiopia. METHODS: A
      cross sectional study was conducted in public health facilities in North Gondar,
      from March 2013 to April 2013. A total number of 297 subjects with suspected
      malaria were enrolled in the study. Finger-prick blood samples were collected and
      examined for Plasmodium parasites using Giemsa microscopy and standard nPCR.
      RESULTS: Among the study participants, 61.6% (183/297) patients tested positive
      for malaria by Giemsa microscopy of which, 72.1% (132/183) and 27.9% (51/183)
      were diagnosed as Plasmodium falciparum and Plasmodium vivax, respectively. By
      nPCR, 73.1% (217/297) were malaria-positive. Among microscopy-negative samples,
      13.1% (39/297) samples turned malaria-positive in nPCR. In nPCR, the rate of
      mixed Plasmodium infections was 4.7% (14/297) and 3.03% (9/297) were positive for
      Plasmodium ovale. Using nPCR as reference the sensitivity, specificity, positive
      predictive and negative predictive values of Giemsa microscopy were 82.0%, 93.8%,
      97.3% and 65.8%, respectively, with a good agreement (kappa = 0.668) to nested
      PCR. The sensitivity and specificity of Giemsa microscopy in identifyingP.
      falciparium infections were 74.0% and 87.4% and 63.2% and 96.5% for P. vivax
      infections, respectively. CONCLUSION: Although Giemsa microscopy remains the gold
      standard for malaria diagnosis in resource-limited environments, its sensitivity
      and specificity as compared to nPCR is limited suggesting exploration of novel
      rapid and simplified molecular techniques for malaria-endemic countries. A high
      rate of misclassification and misidentification highlights the importance of
      adequate training for staff involved in malaria diagnosis.

PMID- 24884607
TI  - The epidemiology of malaria and anaemia in the Bonikro mining area, central Cote
      d'Ivoire.
AB  - BACKGROUND: The epidemiology of malaria and anaemia is characterized by small
      scale spatial and temporal heterogeneity, which might be influenced by human
      activities, such as mining and related disturbance of the environment. Private
      sector involvement holds promise to foster public health, including the
      prevention and control of malaria and anaemia. Here, results from a cross
      sectional epidemiological survey, conducted in communities that might potentially
      be affected by the Bonikro Gold Mine (BGM) in Cote d'Ivoire, are reported.
      METHODS: In December 2012, a cross-sectional survey was carried out in seven
      communities situated within a 20-km radius of the BGM in central Cote d'Ivoire.
      Capillary blood samples were obtained from children aged six to 59 months.
      Samples were subjected to a rapid diagnostic test (RDT) for Plasmodium falciparum
      detection, whilst haemoglobin (Hb) was measured to determine anaemia.
      Additionally, mothers were interviewed with a malaria-related knowledge,
      attitudes and practices questionnaire. RESULTS: A total of 339 children and 235
      mothers participated in the surveys. A positive RDT for P. falciparum was found
      in 69% of the children, whilst 72% of the children were anaemic (Hb <11 g/dl).
      Plasmodium falciparum infection was significantly associated with anaemia (odds
      ratio (OR) 7.43, 95% confidence interval (CI) 3.97-13.89), access to a health
      facility (OR 5.59, 95% CI 1.81-17.32) and age (OR 0.04, 95% CI 0.01-0.12;
      youngest (six to 11 months) versus oldest (48-59 months) age group). Less than a
      quarter of mothers knew that malaria is uniquely transmitted by mosquitoes
      (22.3%, 95% CI 16.8-27.7%). Misconceptions were common; most of the mothers
      believe that working in the sun can cause malaria. CONCLUSIONS: Malaria and
      anaemia are highly endemic in the surveyed communities around the BGM project
      area in Cote d'Ivoire. The data presented here provide a rationale for designing
      setting-specific interventions and can be utilized as a benchmark for
      longitudinal monitoring of potential project-related impacts due to changes in
      the social-ecological and health systems.

PMID- 24884608
TI  - The nucleolar size is associated to the methylation status of ribosomal DNA in
      breast carcinomas.
AB  - BACKGROUND: There is a body of evidence that shows a link between tumorigenesis
      and ribosome biogenesis. The precursor of mature 18S, 28S and 5.8S ribosomal RNAs
      is transcribed from the ribosomal DNA gene (rDNA), which exists as 300-400 copies
      in the human diploid genome. Approximately one half of these copies are
      epigenetically silenced, but the exact role of epigenetic regulation on ribosome
      biogenesis is not completely understood. In this study we analyzed the
      methylation profiles of the rDNA promoter and of the 5' regions of 18S and 28S in
      breast cancer. METHODS: We analyzed rDNA methylation in 68 breast cancer tissues
      of which the normal counterpart was partially available (45/68 samples) using the
      MassARRAY EpiTYPER assay, a sensitive and quantitative method with single base
      resolution. RESULTS: We found that rDNA locus tended to be hypermethylated in
      tumor compared to matched normal breast tissues and that the DNA methylation
      level of several CpG units within the rDNA locus was associated to nuclear grade
      and to nucleolar size of tumor tissues. In addition we identified a subgroup of
      samples in which large nucleoli were associated with very limited or absent rDNA
      hypermethylation in tumor respect to matched normal tissue. CONCLUSIONS: In
      conclusion, we suggest that rDNA is an important target of epigenetic regulation
      in breast tumors and that rDNA methylation level is associated to nucleolar size.

PMID- 24884609
TI  - Site-specific glycan microheterogeneity of inter-alpha-trypsin inhibitor heavy
      chain H4.
AB  - Inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4) is a 120 kDa acute-phase
      glycoprotein produced primarily in the liver, secreted into the blood, and
      identified in serum. ITIH4 is involved in liver development and stabilization of
      the extracellular matrix (ECM), and its expression is altered in liver disease.
      In this study, we aimed to characterize glycosylation of recombinant and serum
      derived ITIH4 using analytical mass spectrometry. Recombinant ITIH4 was analyzed
      to optimize glycopeptide analyses, followed by serum-derived ITIH4. First, we
      confirmed that the four ITIH4 N-X-S/T sequons (N81, N207, N517, and N577) were
      glycosylated by treating ITIH4 tryptic/GluC glycopeptides with PNGaseF in the
      presence of (18)O water. Next, we performed glycosidase-assisted LC-MS/MS
      analysis of ITIH4 trypsin-GluC glycopeptides enriched via hydrophilic interaction
      liquid chromatography to characterize ITIH4 N-glycoforms. While
      microheterogeneity of N-glycoforms differed between ITIH4 protein expressed in
      HEK293 cells and protein isolated from serum, occupancy of N-glycosylation sites
      did not differ. A fifth N-glycosylation site was discovered at N274 with the rare
      nonconsensus NVV motif. Site N274 contained high-mannose N-linked glycans in both
      serum and recombinant ITIH4. We also identified isoform-specific ITIH4 O
      glycoforms and documented that utilization of O-glycosylation sites on ITIH4
      differed between the cell line and serum. 

PMID- 24884610
TI  - Molecular characterization of clinical multidrug-resistant Klebsiella pneumoniae
      isolates.
AB  - BACKGROUND: Klebsiella pneumoniae is a frequent nosocomial pathogen, with the
      multidrug-resistant (MDR) K. pneumoniae being a major public health concern,
      frequently causing difficult-to-treat infections worldwide. The aim of this study
      was to investigate the molecular characterization of clinical MDR Klebsiella
      pneumoniae isolates. METHODS: A total of 27 non-duplicate MDR K. pneumoniae
      isolates with a CTX-CIP-AK resistance pattern were investigated for the
      prevalence of antimicrobial resistance genes including extended spectrum beta
      lactamase genes (ESBLs), plasmid-mediated quinolone resistance (PMQR) genes, 16S
      rRNA methylase (16S-RMTase) genes, and integrons by polymerase chain reaction
      (PCR) amplification and DNA sequencing. Plasmid replicons were typed by PCR-based
      replicon typing (PBRT). Multi-locus sequence typing (MLST) and pulsed-field gel
      electrophoresis (PFGE) were carried out to characterize the strain relatedness.
      RESULTS: All the isolates co-harbored 3 or more resistance determinants. OqxAB,
      CTX-M-type ESBLs and RmtB were the most frequent determinants, distributed among
      19 (70.4%),18 (66.7%) and 8 (29.6%) strains. Fourteen isolates harbored class 1
      integrons, with orfD-aacA4 being the most frequent gene cassette array. Class 3
      integrons were less frequently identified and contained the gene cassette array
      of blaGES-1-blaOXA-10-aac(6')-Ib. IncFII replicon was most commonly found in this
      collection. One cluster was observed with >=80% similarity among profiles
      obtained by PFGE, and one sequence type (ST) by MLST, namely ST11, was observed
      in the cluster. CONCLUSION: K. pneumoniae carbapenemase (KPC)-producing ST11 was
      the main clone detected. Of particular concern was the high prevalence of
      multiple resistance determinants, classs I integrons and IncFII plasmid replicon
      among these MDR strains, which provide advantages for the rapid development of
      MDR strains.

PMID- 24884611
TI  - An easy method to differentiate retinal arteries from veins by spectral domain
      optical coherence tomography: retrospective, observational case series.
AB  - BACKGROUND: Recently it was shown that retinal vessel diameters could be measured
      using spectral domain optical coherence tomography (OCT). It has also been
      suggested that retinal vessels manifest different features on spectral domain OCT
      (SD-OCT) depending on whether they are arteries or veins. Our study was aimed to
      present a reliable SD-OCT assisted method of differentiating retinal arteries
      from veins. METHODS: Patients who underwent circular OCT scans centred at the
      optic disc using a Spectralis OCT (Heidelberg Engineering, Heidelberg, Germany)
      were retrospectively reviewed. Individual retinal vessels were identified on
      infrared reflectance (IR) images and given unique labels for subsequent grading.
      Vessel types (artery, vein or uncertain) assessed by IR and/or fluorescein
      angiography (FA) were referenced as ground truth. From OCT, presence/absence of
      the hyperreflective lower border reflectivity feature was assessed. Presence of
      this feature was considered indicative for retinal arteries and compared with the
      ground truth. RESULTS: A total of 452 vessels from 26 eyes of 18 patients were
      labelled and 398 with documented vessel type (302 by IR and 96 by FA only) were
      included in the study. Using SD-OCT, 338 vessels were assigned a final grade, of
      which, 86.4% (292 vessels) were classified correctly. Forty three vessels (15
      arteries and 28 veins) that IR failed to differentiate were correctly classified
      by SD-OCT. When using only IR based ground truth for vessel type the SD-OCT based
      classification approach reached a sensitivity of 0.8758/0.9297, and a specificity
      of 0.9297/0.8758 for arteries/veins, respectively. CONCLUSION: Our method was
      able to classify retinal arteries and veins with a commercially available SD-OCT
      alone, and achieved high classification performance. Paired with OCT based vessel
      measurements, our study has expanded the potential clinical implication of SD-OCT
      in evaluation of a variety of retinal and systemic vascular diseases.

PMID- 24884612
TI  - Overexpression of CIP2A is an independent prognostic indicator in nasopharyngeal
      carcinoma and its depletion suppresses cell proliferation and tumor growth.
AB  - BACKGROUND: Cancerous inhibitor of protein phosphatase 2A (CIP2A) is an
      oncoprotein that acts as a prognostic marker for several human malignancies. In
      this study, we investigated the clinical significance of CIP2A and its function
      in nasopharyngeal carcinoma (NPC). METHODS: Quantitative RT-PCR, western blot,
      and immunohistochemistry analyses were used to quantify CIP2A expression in NPC
      cell lines and clinical samples. Kaplan-Meier curves were used to estimate the
      association between CIP2A expression and patient survival. The functional role of
      CIP2A in NPC cell lines was evaluated by small interfering RNA-mediated depletion
      of the protein followed by analyses of cell proliferation and xenograft growth.
      RESULTS: CIP2A levels were upregulated in NPC cell lines and clinical samples at
      both the mRNA and protein levels (P < 0.01). Patients with high CIP2A expression
      had poorer overall survival (HR, 1.98; 95% CI, 1.16-3.34; P = 0.01) and poorer
      disease-free survival (HR, 1.68; 95% CI, 1.07-2.62; P = 0.02) rates than patients
      with low CIP2A expression. In addition, CIP2A expression status was an
      independent prognostic indicator for NPC patients. The depletion of CIP2A
      expression inhibited c-Myc protein expression in NPC cell lines, suppressed cell
      viability, colony formation, and anchorage-independent growth in vitro, and
      inhibited xenograft tumor growth in vivo. CONCLUSIONS: Our data demonstrate that
      high CIP2A expression in patients was associated with poor survival in NPC, and
      depletion of CIP2A expression inhibited NPC cell proliferation and tumor growth.
      Thus, these results warrant further investigation of CIP2A as a novel therapeutic
      target for the treatment of NPC.

PMID- 24884613
TI  - An amino acid-electrolyte beverage may increase cellular rehydration relative to
      carbohydrate-electrolyte and flavored water beverages.
AB  - BACKGROUND: In cases of dehydration exceeding a 2% loss of body weight, athletic
      performance can be significantly compromised. Carbohydrate and/or electrolyte
      containing beverages have been effective for rehydration and recovery of
      performance, yet amino acid containing beverages remain unexamined. Therefore,
      the purpose of this study is to compare the rehydration capabilities of an
      electrolyte-carbohydrate (EC), electrolyte-branched chain amino acid (EA), and
      flavored water (FW) beverages. METHODS: Twenty men (n = 10; 26.7 +/- 4.8 years;
      174.3 +/- 6.4 cm; 74.2 +/- 10.9 kg) and women (n = 10; 27.1 +/- 4.7 years; 175.3
      +/- 7.9 cm; 71.0 +/- 6.5 kg) participated in this crossover study. For each
      trial, subjects were dehydrated, provided one of three random beverages, and
      monitored for the following three hours. Measurements were collected prior to and
      immediately after dehydration and 4 hours after dehydration (3 hours after
      rehydration) (AE = -2.5 +/- 0.55%; CE = -2.2 +/- 0.43%; FW = -2.5 +/- 0.62%).
      Measurements collected at each time point were urine volume, urine specific
      gravity, drink volume, and fluid retention. RESULTS: No significant differences
      (p > 0.05) existed between beverages for urine volume, drink volume, or fluid
      retention for any time-point. Treatment x time interactions existed for urine
      specific gravity (USG) (p < 0.05). Post hoc analysis revealed differences
      occurred between the FW and EA beverages (p = 0.003) and between the EC and EA
      beverages (p = 0.007) at 4 hours after rehydration. Wherein, EA USG returned to
      baseline at 4 hours post-dehydration (mean difference from pre to 4 hours post
      dehydration = -0.0002; p > 0.05) while both EC (-0.0067) and FW (-0.0051)
      continued to produce dilute urine and failed to return to baseline at the same
      time-point (p < 0.05). CONCLUSION: Because no differences existed for fluid
      retention, urine or drink volume at any time point, yet USG returned to baseline
      during the EA trial, an EA supplement may enhance cellular rehydration rate
      compared to an EC or FW beverage in healthy men and women after acute dehydration
      of around 2% body mass loss.

PMID- 24884614
TI  - Suggestions to ameliorate the inequity in urban/rural allocation of healthcare
      resources in China.
AB  - The imbalance in the allocation in healthcare resources between urban and rural
      areas has become a main focus of the recent medical reforms adopted in China.
      However, systematic analysis has identified wide differences in the allocation of
      healthcare resources between urban and rural areas, including healthcare
      expenditures and the number of healthcare facilities, available beds, and
      personnel. Therefore, the aim of this report was to identify ethical
      considerations in current governmental policies to rectify existing problems in
      the distribution of healthcare resources. Our findings indicate that the
      inequality in the distribution of healthcare resources does not adhere to ethical
      standards and the policies are flawed because they give rise to differences in
      the availability of medical care to urban and rural communities. To optimize the
      allocation of medical healthcare resources, countermeasures are proposed to
      formulate policies to urge the flow of public healthcare resources to rural
      areas, strengthen the responsibilities of both governmental and public financial
      investments, increase the construction of public healthcare facilities in rural
      areas, promote the quality of healthcare resources, adjust resource allocations
      to rural public healthcare facilities, and improve resource utilization
      efficiency by establishing two-way referral mechanisms. 

PMID- 24884616
TI  - A 6-month "self-monitoring" lifestyle modification with increased sunlight
      exposure modestly improves vitamin D status, lipid profile and glycemic status in
      overweight and obese Saudi adults with varying glycemic levels.
AB  - BACKGROUND: The over-all age-adjusted prevalence of diabetes mellitus type 2
      (DMT2) in Saudi Arabia is unprecedented at 31%. Aggressive measures should be
      done to curb down increasing incidence. In this prospective 6-month study we aim
      to determine whether a self-monitoring, life-style modification program that
      includes increased sunlight exposure confer improvement in vitamin D status and
      health benefits among adult Saudi overweight and obese patients with varying
      glycemic status. METHODS: A total of 150 overweight and obese Saudi adults with
      varying glycemic status aged 30-60 years were included in this study. They were
      divided into 3 groups (Non-DMT2, Pre-diabetes and DMT2). Baseline anthropometrics
      and blood glucose were taken at baseline and after 6 months. Fasting blood sugar,
      lipid profile, calcium, albumin and phosphate were measured routinely. Serum
      25(OH) vitamin D was measured using standard assays. Within the time period they
      were instructed to reduce total intake of fat, increased fiber intake and
      increase sun exposure. RESULTS: In all groups there was a significant improvement
      in vitamin D levels as well as serum triglycerides, LDL- and total cholesterol.
      However, a significant increase in serum glucose levels was noted in the non-DMT2
      group, and a significant decrease in HDL-cholesterol in both non-DMT2 and pre
      diabetes group. In the pre-diabetes group, 53.2% were able to normalize their
      fasting blood levels after 6 months, with 8.5% reaching the DMT2 stage and 38.3%
      remaining pre-diabetic. In all groups there was a significant increase in the
      prevalence of hypertension. CONCLUSION: Improving vitamin D status with modest
      lifestyle modifications over a short-period translates to improvement in lipid
      profile except HDL-cholesterol among overweight and obese Saudi adults, but not
      BMI and blood pressure. Findings of the present study merit further investigation
      as to whether full vitamin D status correction can delay or prevent onset of
      DMT2.

PMID- 24884615
TI  - Complete genome sequence and comparative genomic analyses of the vancomycin
      producing Amycolatopsis orientalis.
AB  - BACKGROUND: Amycolatopsis orientalis is the type species of the genus and its
      industrial strain HCCB10007, derived from ATCC 43491, has been used for large
      scale production of the vital antibiotic vancomycin. However, to date, neither
      the complete genomic sequence of this species nor a systemic characterization of
      the vancomycin biosynthesis cluster (vcm) has been reported. With only the whole
      genome sequence of Amycolatopsis mediterranei available, additional complete
      genomes of other species may facilitate intra-generic comparative analysis of the
      genus. RESULTS: The complete genome of A. orientalis HCCB10007 comprises an
      8,948,591-bp circular chromosome and a 33,499-bp dissociated plasmid. In total,
      8,121 protein-coding sequences were predicted, and the species-specific genomic
      features of A. orientalis were analyzed in comparison with that of A.
      mediterranei. The common characteristics of Amycolatopsis genomes were revealed
      via intra- and inter-generic comparative genomic analyses within the domain of
      actinomycetes, and led directly to the development of sequence-based
      Amycolatopsis molecular chemotaxonomic characteristics (MCCs). The chromosomal
      core/quasi-core and non-core configurations of the A. orientalis and the A.
      mediterranei genome were analyzed reciprocally, with respect to further
      understanding both the discriminable criteria and the evolutionary
      implementation. In addition, 26 gene clusters related to secondary metabolism,
      including the 64-kb vcm cluster, were identified in the genome. Employing a
      customized PCR-targeting-based mutagenesis system along with the biochemical
      identification of vancomycin variants produced by the mutants, we were able to
      experimentally characterize a halogenase, a methyltransferase and two
      glycosyltransferases encoded in the vcm cluster. The broad substrate spectra
      characteristics of these modification enzymes were inferred. CONCLUSIONS: This
      study not only extended the genetic knowledge of the genus Amycolatopsis and the
      biochemical knowledge of vcm-related post-assembly tailoring enzymes, but also
      developed methodology useful for in vivo studies in A. orientalis, which has been
      widely considered as a barrier in this field.

PMID- 24884617
TI  - Cancer risks among patients with type 2 diabetes: a 10-year follow-up study of a
      nationwide population-based cohort in Taiwan.
AB  - BACKGROUND: This study aims to determine cancer risks among patients with type 2
      diabetes through a follow-up study on a nationwide population-based cohort that
      included Taiwanese diabetic patients and general population in Taiwan as well as
      to estimate the population attributable fraction (PAF) of site-specific cancer
      risks that can be attributed to type 2 diabetes in Taiwanese population by using
      standardized incidence ratios (SIRs, 95% CI). METHODS: Subjects with type 2
      diabetes consisted of 472,979 patients aged >= 20 years, whereas general
      population consisted of 9,411,249 individuals of the same age limit but are not
      diabetic. Subjects were identified from 1997 to 1998 and followed up until
      December 31, 2007 or until the first manifestation of any cancer. RESULTS: Cancer
      sites with increased risks in men, which were consistent with the main and
      sensitivity analyses, included pancreas (SIR=1.62; 95% CI=1.53 to 1.72), liver
      (1.61; 1.57 to 1.64), kidney (1.32; 1.25 to 1.40), oral (1.16, 1.12 to 1.21), and
      colorectal (1.19, 1.15 to 1.22). Cancer sites with increased risks in women
      included liver (1.55; 1.51 to 1.60), pancreas (1.44; 1.34 to 1.55), kidney (1.38;
      1.30 to 1.46), endometrium (1.36; 1.26 to 1.47), bladder (1.19; 1.11 to 1.27),
      colorectal (1.16; 1.13 to 1.20), and breast (1.14; 1.09 to 1.18). Overall, PAFs
      were highest for liver cancer in men (4.0%) and women (3.7%), followed by
      pancreas (3.4%) and kidney (1.6%) cancers in men, and then for endometrium (1.8%)
      and kidney (1.8%) cancers in women. CONCLUSION: Our data suggested that increased
      cancer risks are associated with type 2 diabetes.

PMID- 24884618
TI  - Landless female peasants living in resettlement residential areas in China have
      poorer quality of life than males: results from a household study in the Yangtze
      River Delta region.
AB  - BACKGROUND: Urbanization has accelerated in China, and a large amount of arable
      land has been transformed into urban land. Moreover, the number of landless
      peasants has continually increased. Peasants lose not only their land, but also a
      series of rights and interests related with land. The problems of landless
      peasants have been long-standing; however, only a few studies have examined their
      health or quality of life (QOL). This paper assesses the QOL of landless peasants
      in the Yangtze River Delta (YRD) region, analyzes gender differences, and
      explores health inequity. METHODS: Data are derived from household samples in six
      resettlement residential areas of three cities (Nanjing, Hangzhou, and Yangzhou)
      in the YRD region (N = 1,500; the effective rate = 82.4%). This study uses the
      short version of World Health Organization Quality of Life questionnaire (WHOQOL
      BREF) scale to measure the QOL of landless peasants, and performs confirmatory
      factor analysis (CFA) and analyze gender differences in QOL on the basis of CFA.
      RESULTS AND CONCLUSION: First, we use Analysis of Variance and Non-parametric
      Tests to test if the differences of mean value of testing generals have
      statistical significances. Results shows significant differences occur between
      the impacts of different genders on the four domains of QOL (physical health,
      psychological health, social relationships, and environment). The internal
      reliability of the WHOQOL-BREF scale is good (Cronbach's alpha > 0.8), and the
      four domains of QOL are connected with each other. Second, scores in each QOL
      domain are commonly low, whereas the scores of females are much lower, indicating
      a poorer QOL than that of males. Third, results of the CFA of the QOL domains and
      their related observed variables indicate a good model fit. Fourth, results imply
      that the order of importance of the four domains (psychological health (males =
      26.74%, females = 27.17%); social relationships (males = 26.23%, females =
      25.35%); environment (males = 25.70%, females = 24.40%); and physical health
      (males = 21.33%, females = 23.08%)) affecting QOL from high to low is the same
      for landless male and female peasants, whereas the proportion of importance is
      different between genders. The results highlight the importance of government
      intervention to improve the QOL of Chinese landless peasants, ultimately reducing
      health inequity.

PMID- 24884619
TI  - Pediatric gastroenteritis in the emergency department: practice evaluation in
      Belgium, France, The Netherlands and Switzerland.
AB  - BACKGROUND: Based on European recommendations of ESPGHAN/ESPID from 2008, first
      line therapy for dehydration caused by acute gastroenteritis (AGE) is oral
      rehydration solution (ORS). In case of oral route failure, nasogastric tube
      enteral rehydration is as efficient as intra-venous rehydration and seems to lead
      to fewer adverse events. The primary objective was to describe rehydration
      strategies used in cases of AGE in pediatric emergency departments (PEDs) in
      Belgium, France, The Netherlands, and Switzerland. METHODS: An electronic survey
      describing a scenario in which a toddler had moderate dehydration caused by AGE
      was sent to physicians working in pediatric emergency departments. Analytical
      data were analyzed with descriptive statistics and Kruskal -Wallis Rank test.
      RESULTS: We analyzed 68 responses, distributed as follows: Belgium N = 10, France
      N = 37, The Netherlands N = 7, and Switzerland N = 14. Oral rehydration with ORS
      was the first line of treatment for 90% of the respondents. In case of first line
      treatment failure, intravenous rehydration was preferred by 95% of respondents
      from France, whereas nasogastric route was more likely to be used by those from
      Belgium (80%), The Netherlands (100%) and Switzerland (86%). Serum electrolyte
      measurements were more frequently prescribed in France (92%) and Belgium (80%)
      than in The Netherlands (43%) and Switzerland (29%). Racecadotril was more
      frequently used in France, and ondansetron was more frequently used in
      Switzerland. No respondent suggested routine use of antibiotics. CONCLUSION: We
      found variations in practices in terms of invasiveness and testing. Our study
      supports the need for further evaluation and implementation strategies of
      ESPGHAN/ESPID guidelines. We plan to extend the study throughout Europe with
      support of the Young ESPID Group.

PMID- 24884620
TI  - Resolution of intussusception after spontaneous expulsion of an ileal lipoma per
      rectum: a case report and literature review.
AB  - We herein report a case of spontaneous rectal expulsion of an ileal lipoma in a
      65-year-old female patient who presented with recurrent attacks of subacute
      intestinal obstruction. During each episode, the patient developed severe
      abdominal pain and expelled a fleshy mass from her rectum. The fleshy mass was
      histopathologically diagnosed as a lipoma comprising fat cells, fibers, and blood
      vessels. Upon expulsion, the pain disappeared and the intussusception was
      immediately resolved. Colonoscopic examination revealed a 2.5-cm diameter
      ulcerated lesion near the ileocecal valve, which was confirmed to be inflammation
      by pathological examination. A subsequent barium series revealed a normal colonic
      tract, and the patient remained completely symptom-free for 4 months after the
      incident. According to the relevant literature and our clinical experience, the
      treatment method for a lipoma depends on the patient's clinical manifestations
      and the size of the tumor. However, the various diagnostic and therapeutic
      modalities currently available continue to be debated; whether an asymptomatic
      lipoma requires treatment is controversial. When histopathological examination
      results allow for the exclusion of malignant lesions such as sarcoma, a lipoma
      can be resected surgically. 

PMID- 24884621
TI  - Gender differences in the association between adiposity and probable major
      depression: a cross-sectional study of 140,564 UK Biobank participants.
AB  - BACKGROUND: Previous studies on the association between adiposity and mood
      disorder have produced contradictory results, and few have used measurements
      other than body mass index (BMI). We examined the association between probable
      major depression and several measurements of adiposity: BMI, waist circumference
      (WC), waist-hip-ratio (WHR), and body fat percentage (BF%). METHODS: We conducted
      a cross-sectional study using baseline data on the sub-group of UK Biobank
      participants who were assessed for mood disorder. Multivariate logistic
      regression models were used, adjusting for potential confounders including:
      demographic and life-style factors, comorbidity and psychotropic medication.
      RESULTS: Of the 140,564 eligible participants, evidence of probable major
      depression was reported by 30,145 (21.5%). The fully adjusted odds ratios (OR)
      for obese participants were 1.16 (95% confidence interval (CI) 1.12, 1.20) using
      BMI, 1.15 (95% CI 1.11, 1.19) using WC, 1.09 (95% CI 1.05, 1.13) using WHR and
      1.18 (95% CI 1.12, 1.25) using BF% (all p < 0.001). There was a significant
      interaction between adiposity and gender (p = 0.001). Overweight women were at
      increased risk of depression with a dose response relationship across the
      overweight (25.0-29.9 kg/m2), obese I (30.0-34.9 kg/m2), II (35.0-39.9 kg/m2) and
      III (>=40.0 kg/m2) categories; fully adjusted ORs 1.14, 1.20, 1.29 and 1.48,
      respectively (all p < 0.001). In contrast, only obese III men had significantly
      increased risk of depression (OR 1.29, 95% CI 1.08, 1.54, p = 0.006). CONCLUSION:
      Adiposity was associated with probable major depression, irrespective of the
      measurement used. The association was stronger in women than men. Physicians
      managing overweight and obese women should be alert to this increased risk.

PMID- 24884622
TI  - The association of ADHD symptoms to self-harm behaviours: a systematic PRISMA
      review.
AB  - BACKGROUND: Self-harm is a major public health issue in young people worldwide
      and there are many challenges to its management and prevention. Numerous studies
      have indicated that ADHD is associated with completed suicides and other suicidal
      behaviours (i.e., suicidal attempt and ideation). However, significantly less is
      known about the association between ADHD and self-harm. METHOD: This is the first
      review of the association between ADHD and self-harm. A systematic PRISMA review
      was conducted. Two internet-based bibliographic databases (Medline and CINAHL)
      were searched to access studies which examined to any degree the association
      between, specifically, ADHD and self-harm. RESULTS: Only 15 studies were
      identified which investigated the association between ADHD and self-harm and
      found evidence to support that ADHD is a potential risk factor for self-harm.
      CONCLUSION: This association raises the need for more awareness of self-harm in
      individuals with symptoms of ADHD.

PMID- 24884623
TI  - Differential expression of small RNAs from Burkholderia thailandensis in response
      to varying environmental and stress conditions.
AB  - BACKGROUND: Bacterial small RNAs (sRNAs) regulate gene expression by base-pairing
      with downstream target mRNAs to attenuate translation of mRNA into protein at the
      post-transcriptional level. In response to specific environmental changes, sRNAs
      can modulate the expression levels of target genes, thus enabling adaptation of
      cellular physiology. RESULTS: We profiled sRNA expression in the Gram-negative
      bacteria Burkholderia thailandensis cultured under 54 distinct growth conditions
      using a Burkholderia-specific microarray that contains probe sets to all
      intergenic regions greater than 90 bases. We identified 38 novel sRNAs and
      performed experimental validation on five sRNAs that play a role in adaptation of
      Burkholderia to cell stressors. In particular, the trans-encoded BTH_s1 and s39
      exhibited differential expression profiles dependent on growth phase and cell
      stimuli, such as antibiotics and serum. Furthermore, knockdown of the highly
      expressed BTH_s39 by antisense transcripts reduced B. thailandensis cell growth
      and attenuated host immune response upon infection, indicating that BTH_s39
      functions in bacterial metabolism and adaptation to the host. In addition,
      expression of cis-encoded BTH_s13 and s19 found in the 5' untranslated regions of
      their cognate genes correlated with tight regulation of gene transcript levels.
      This sRNA-mediated downregulation of gene expression may be a conserved mechanism
      of post-transcriptional gene dosage control. CONCLUSIONS: These studies provide a
      broad analysis of differential Burkholderia sRNA expression profiles and
      illustrate the complexity of bacterial gene regulation in response to different
      environmental stress conditions.

PMID- 24884624
TI  - Management of brain metastases with stereotactic radiosurgery alone versus whole
      brain irradiation alone versus both.
AB  - INTRODUCTION: This prospective randomized study aimed to evaluate the role of
      WBRT + SRS compared to SRS alone and to WBRT alone in improvement of overall
      survival, brain local control and neurologic manifestations. PATIENTS AND
      METHODS: The trial included 60 patients with 1 to 3 brain metastases treated at
      the Radiotherapy Department, National Cancer Institute. 21 patients received WBRT
      + SRS, 18 patients received SRS alone and 21 patients received WBRT alone.
      RESULTS: Median local control was significantly better for WBRT + SRS compared to
      SRS alone & WBRT alone (10 vs 6 vs 5 months, respectively, P = 0.04). There was
      non significant survival benefit for WBRT + SRS compared to SRS alone & WBRT
      alone. Survival was significantly better for patients with controlled primary
      tumor who received WBRT + SRS compared to SRS alone & WBRT alone (median survival
      was 12 vs 5.5 vs 8 months, respectively. P = 0.027). Regardless of the treatment
      group, median survival and median local control were highly significantly better
      for single brain site involvement compared to multiple brain sites involvement (P
      = 0.003 & P = 0.001, respectively), and median brain local control was
      significantly better for single lesion compared to multiple lesions (P = 0.05).
      CONCLUSIONS: WBRT + SRS is an effective, safe tool in treatment of patients with
      1 to 3 brain metastses improving the brain local control, but further studies
      with larger number of patients is recommended.

PMID- 24884626
TI  - Is fibrin sealant effective and safe in total knee arthroplasty? A meta-analysis
      of randomized trials.
AB  - The objective of this study was to evaluate the efficacy and safety of fibrin
      sealant in patients following total knee arthroplasty (TKA). A comprehensive
      literature search of the electronic databases PubMed, MEDLINE, Web of Science,
      and Cochrane Library for published randomized controlled trials (RCTs) was
      undertaken. The evidence base was critically appraised using a tool from the
      Cochrane Bone, Joint and Muscle Trauma Group. Eight RCTs involving 641 patients
      were included. The use of fibrin sealant significantly reduced postoperative
      drainage (weighted mean difference (WMD) -346, 95% confidence interval (CI) 
      496.29 to -197.54, P < 0.00001) and blood transfusions (risk ratio (RR) 0.47, 95%
      CI 0.35 to 0.63, P < 0.00001) and led to a significant improvement in the range
      of motion (WMD 16.59, 95% CI 6.92 to 26.25, P = 0.0008). However, using fibrin
      sealant did not significantly reduced total blood loss (WMD -305.25, 95% CI 
      679.44 to 68.95, P = 0.11). Regarding complications, there were no significant
      differences in any adverse events, fever, infection, or hematoma among the study
      groups. In conclusion, the present meta-analysis indicates that the use of fibrin
      sealant was effective and safe as a hemostatic therapy for patients with TKA. 

PMID- 24884625
TI  - Complete sequences of organelle genomes from the medicinal plant Rhazya stricta
      (Apocynaceae) and contrasting patterns of mitochondrial genome evolution across
      asterids.
AB  - BACKGROUND: Rhazya stricta is native to arid regions in South Asia and the Middle
      East and is used extensively in folk medicine to treat a wide range of diseases.
      In addition to generating genomic resources for this medicinally important plant,
      analyses of the complete plastid and mitochondrial genomes and a nuclear
      transcriptome from Rhazya provide insights into inter-compartmental transfers
      between genomes and the patterns of evolution among eight asterid mitochondrial
      genomes. RESULTS: The 154,841 bp plastid genome is highly conserved with gene
      content and order identical to the ancestral organization of angiosperms. The
      548,608 bp mitochondrial genome exhibits a number of phenomena including the
      presence of recombinogenic repeats that generate a multipartite organization,
      transferred DNA from the plastid and nuclear genomes, and bidirectional DNA
      transfers between the mitochondrion and the nucleus. The mitochondrial genes sdh3
      and rps14 have been transferred to the nucleus and have acquired targeting
      presequences. In the case of rps14, two copies are present in the nucleus; only
      one has a mitochondrial targeting presequence and may be functional. Phylogenetic
      analyses of both nuclear and mitochondrial copies of rps14 across angiosperms
      suggests Rhazya has experienced a single transfer of this gene to the nucleus,
      followed by a duplication event. Furthermore, the phylogenetic distribution of
      gene losses and the high level of sequence divergence in targeting presequences
      suggest multiple, independent transfers of both sdh3 and rps14 across asterids.
      Comparative analyses of mitochondrial genomes of eight sequenced asterids
      indicates a complicated evolutionary history in this large angiosperm clade with
      considerable diversity in genome organization and size, repeat, gene and intron
      content, and amount of foreign DNA from the plastid and nuclear genomes.
      CONCLUSIONS: Organelle genomes of Rhazya stricta provide valuable information for
      improving the understanding of mitochondrial genome evolution among angiosperms.
      The genomic data have enabled a rigorous examination of the gene transfer events.
      Rhazya is unique among the eight sequenced asterids in the types of events that
      have shaped the evolution of its mitochondrial genome. Furthermore, the organelle
      genomes of R. stricta provide valuable genomic resources for utilizing this
      important medicinal plant in biotechnology applications.

PMID- 24884627
TI  - Fibrinogen concentrate administration attributes to significant reductions of
      blood loss and transfusion requirements in thoracic aneurysm repair.
AB  - BACKGROUND: Repair of thoracic aortic aneurysm (TAA) is often associated with
      massive hemorrhage aggravated by dilutional coagulopathy with severe
      hypofibrinogenemia. Although only fresh frozen plasma (FFP) is available for
      acquired hypofibrinogenemia in Japan, the hemostatic effect of FFP has not been
      enough for dilutional coagulopathy in TAA surgery. There are increasing reports
      suggesting that fibrinogen concentrate may be effective in controlling
      perioperative bleeding and reducing transfusion requirements. METHODS: We
      retrospectively analyzed the hemostatic effect of fibrinogen concentrate compared
      with FFP in total 49 cases of elective TAA surgery. In 25 patients, fibrinogen
      concentrate was administered when the fibrinogen level was below 150 mg/dL at the
      cardiopulmonary bypass (CPB) termination. The recovery of fibrinogen level, blood
      loss, and transfused units during surgery were compared between cases of this
      agent and FFP (n = 24). RESULTS: We observed rapid increases in plasma fibrinogen
      level and subsequent improvement in hemostasis by administration of fibrinogen
      concentrate after CPB termination. The average volume of total blood loss
      decreased by 64% and the average number of transfused units was reduced by 58% in
      cases of fibrinogen concentrate given, in comparison with cases of only FFP
      transfused for fibrinogen supplementation. CONCLUSIONS: In patients showing
      severe hypofibrinogenemia during TAA surgery, timely administration of fibrinogen
      concentrate just after removal from CPB is effective for hemostasis, and
      therefore in reducing blood loss and transfused volumes.

PMID- 24884628
TI  - Ovulation but not milt production is inhibited in fathead minnows (Pimephales
      promelas) exposed to a reproductively inhibitory pulp mill effluent.
AB  - BACKGROUND: A 5-day fathead minnow (FHM) spawning assay is used by industry to
      monitor pulp mill effluent quality, with some mill effluents capable of
      completely inhibiting spawning. The purpose of this report is to characterize the
      effect of an inhibitory effluent on egg and milt production in FHM. METHODS:
      Eight tanks were treated with an inhibitory effluent while eight were kept with
      clean water. Each tank contained two males and four females as per the 5-day FHM
      spawning assay used by industry. Females were stripped of ovulated eggs and males
      of milt in four effluent-exposed and four control tanks. Eggs oviposited in every
      tank were also counted and checked for fertilization and data analyzed with 2-way
      ANOVA. RESULTS: We show that female, but not male, fathead minnow reproductive
      function is impaired in the 5-day fathead minnow spawning assay used by industry
      to evaluate pulp mill effluent quality in Canada. Milt production was not changed
      in the control or exposed males mid-way and at the end of the five day exposure
      (p > 0.05; n = 8). Total egg production (stripped + oviposited) was impaired (p <
      0.05) in fathead minnows exposed to effluent (288 eggs/tank, n = 4 tanks)
      compared to those in control tanks (753 eggs/tank, n = 4 tanks). CONCLUSIONS: Our
      results indicate that males are able to detect female signals and prepare
      appropriately for spawning while in females inhibition of ovulation is occurring
      somewhere along the hypothalamus-pituitary-gonad reproductive axis. These results
      suggest female-specific neuroendocrine disruption and provide mechanistic insight
      into an assay used by industry to assess pulp mill effluent quality.

PMID- 24884630
TI  - A mechanically-induced colon cancer cell population shows increased metastatic
      potential.
AB  - BACKGROUND: Metastasis accounts for the majority of deaths from cancer. Although
      tumor microenvironment has been shown to have a significant impact on the
      initiation and/or promotion of metastasis, the mechanism remains elusive. We
      previously reported that HCT-8 colon cancer cells underwent a phenotypic
      transition from an adhesive epithelial type (E-cell) to a rounded dissociated
      type (R-cell) via soft substrate culture, which resembled the initiation of
      metastasis. The objective of current study was to investigate the molecular and
      metabolic mechanisms of the E-R transition. METHODS: Global gene expressions of
      HCT-8 E and R cells were measured by RNA Sequencing (RNA-seq); and the results
      were further confirmed by real-time PCR. Reactive oxygen species (ROS), anoikis
      resistance, enzyme activity of aldehyde dehydrogenase 3 family, member A1
      (ALDH3A1), and in vitro invasion assay were tested on both E and R cells. The
      deformability of HCT-8 E and R cells was measured by atomic force microscopy
      (AFM). To study the in vivo invasiveness of two cell types, athymic nude mice
      were intra-splenically injected with HCT-8 E or R cells and sacrificed after 9
      weeks. Incidences of tumor development and metastasis were histologically
      evaluated and analyzed with Fisher's exact test. RESULTS: Besides HCT-8, E-R
      transition on soft substrates was also seen in three other cancer cell lines
      (HCT116, SW480 colon and DU145 prostate cancer). The expression of some genes,
      such as ALDH3A1, TNS4, CLDN2, and AKR1B10, which are known to play important
      roles in cancer cell migration, invasion, proliferation and apoptosis, were
      increased in HCT-8 R cells. R cells also showed higher ALDH3A1 enzyme activity,
      higher ROS, higher anoikis resistance, and higher softness than E cells. More
      importantly, in vitro assay and in vivo animal models revealed that HCT-8 R cells
      were more invasive than E cells. CONCLUSIONS: Our comprehensive comparison of HCT
      8 E and R cells revealed differences of molecular, phenotypical, and mechanical
      signatures between the two cell types. To our knowledge, this is the first study
      that explores the molecular mechanism of E-R transition, which may greatly
      increase our understanding of the mechanisms of cancer mechanical
      microenvironment and initiation of cancer metastasis.

PMID- 24884631
TI  - Free posterior tibial flap reconstruction for hypopharyngeal squamous cell
      carcinoma.
AB  - OBJECTIVES: The aim of this article was to determine outcomes in patients with
      squamous cell carcinoma of the hypopharynx (SCCHP) in whom the free posterior
      tibial flap was used for primary reconstruction of hypopharynx defects after
      cancer resection. SUBJECTS AND METHODS: Between August 2009 and February 2012, 10
      patients with SCCHP underwent posterior tibial flap reconstruction for
      hypopharynx defects. The corresponding clinical data were retrospectively
      collected and analyzed. RESULTS: Despite the multistep and time-consuming
      procedure, the posterior tibial flap survival rate was 100%. Operation-induced
      complications did not occur in four patients. Six patients developed
      postoperative hypoproteinemia, four patients developed postoperative pulmonary
      infections, and four patients developed pharyngeal fistula. The pharyngeal and
      laryngeal functions of all patients were preserved. CONCLUSION: Our experience
      demonstrates that the posterior tibial flap is a safe and reliable choice for the
      reconstruction of hypopharynx defects.

PMID- 24884632
TI  - Sequence analysis for detection of drug resistance in Mycobacterium tuberculosis
      complex isolates from the Central Region of Cameroon.
AB  - BACKGROUND: The potential of genetic testing to rapidly diagnose drug resistance
      has lead to the development of new diagnostic assays. However, prior to
      implementation in a given setting, the association of specific mutations with
      specific drug resistance phenotypes should be evaluated. The purpose of this
      study was to evaluate molecular markers in predicting drug resistance in the
      Central Region of Cameroon. RESULTS: From April 2010 and March 2011, 725 smear
      positive pulmonary tuberculosis patients were enrolled and all positive cultures
      were tested for drug susceptibility. A total of 63 drug resistant and 100 drug
      sensitive Mycobacterium tuberculosis complex clinical isolates were screened for
      genetic mutations in katG, inhA, ahpC, rpoB, rpsL, rrs, gidB and embCAB loci
      using DNA sequencing. Of the 44 isoniazid resistant (INHR) isolates (24 high
      level, 1 MUg/ml and 20 low level, 0.2 MUg/ml), 73% (32/44) carried the katG315
      and/or the -15 inhA promoter mutations. Of the 24 high level INHR, 17 (70.8%)
      harbored katG315 mutation, 1 a point mutation (-15C -> T) in the inhA promoter
      and 6 were (25.0%) wild types. Thus, for INHR high level detection, katG315
      mutation had a specificity and a sensitivity of 100% and 70.8% respectively. Of
      the 20 low level INHR, 10 (50.0%) had a -15C -> T mutation in the inhA promoter
      region, and 1 (2.2%) a -32G -> A mutation in the ahpC promoter region. All of the
      7 rifampicin resistant (RIFR) isolates carried mutations in the rpoB gene (at
      codons Ser531Leu (71.4%), His526Asp (14.3%), and Asp516Val (14.3%)). Of the 27
      streptomycin resistant (SMR) isolates, 7 carried mutations at the rpsL and the
      gidB genes. 1 of the 2 ethambutol resistant (EMBR) isolates displayed a mutation
      in embB gene. CONCLUSION: This study provided the first molecular investigation
      assessing the correlation of phenotypic to genotypic characteristics on MTB
      isolates from the Central Region of Cameroon using DNA sequencing. Mutations on
      rpoB, katG315 and -15 point mutations in inhA promoter loci could be used as
      markers for RIF and INH -resistance detection respectively.

PMID- 24884633
TI  - Prevalence of human immunodeficiency virus, syphilis, hepatitis B and C in blood
      donations in Namibia.
AB  - BACKGROUND: Transfusion Transmissible Infections (TTIs) such as Human
      Immunodeficiency Virus (HIV), syphilis, hepatitis B virus (HBV) and hepatitis C
      virus (HCV) are infections which are common in some communities in Southern
      Africa. It is important to screen blood donations for these infections. METHODS:
      This is a retrospective study which involved reviewing of previous blood donation
      records for the year 2012 in Namibia. The records were analyzed to determine the
      prevalence of HIV, syphilis, Hepatitis B and C among blood donations with regard
      to gender, age and geographical region of the donors. RESULTS: The findings
      indicated a significantly low prevalence of HIV, syphilis, HBsAg and anti
      Hepatitis C among the blood donations. A low infection rate of 1.3% by any of the
      four tested TTIs was found among the blood donations given by the donor
      population in Namibia in 2012. CONCLUSION: The blood donations given by the donor
      population in Namibia has a low infection rate with the HIV, syphilis, HBsAg and
      anti-HCV. A strict screening regime must continue to be used as the infections
      are still present albeit in small numbers.

PMID- 24884629
TI  - CNS involvement in OFD1 syndrome: a clinical, molecular, and neuroimaging study.
AB  - BACKGROUND: Oral-facial-digital type 1 syndrome (OFD1; OMIM 311200) belongs to
      the expanding group of disorders ascribed to ciliary dysfunction. With the aim of
      contributing to the understanding of the role of primary cilia in the central
      nervous system (CNS), we performed a thorough characterization of CNS involvement
      observed in this disorder. METHODS: A cohort of 117 molecularly diagnosed OFD
      type I patients was screened for the presence of neurological symptoms and/or
      cognitive/behavioral abnormalities on the basis of the available information
      supplied by the collaborating clinicians. Seventy-one cases showing CNS
      involvement were further investigated through neuroimaging studies and
      neuropsychological testing. RESULTS: Seventeen patients were molecularly
      diagnosed in the course of this study and five of these represent new mutations
      never reported before. Among patients displaying neurological symptoms and/or
      cognitive/behavioral abnormalities, we identified brain structural anomalies in
      88.7%, cognitive impairment in 68%, and associated neurological disorders and
      signs in 53% of cases. The most frequently observed brain structural anomalies
      included agenesis of the corpus callosum and neuronal migration/organisation
      disorders as well as intracerebral cysts, porencephaly and cerebellar
      malformations. CONCLUSIONS: Our results support recent published findings
      indicating that CNS involvement in this condition is found in more than 60% of
      cases. Our findings correlate well with the kind of brain developmental anomalies
      described in other ciliopathies. Interestingly, we also described specific
      neuropsychological aspects such as reduced ability in processing verbal
      information, slow thought process, difficulties in attention and concentration,
      and notably, long-term memory deficits which may indicate a specific role of OFD1
      and/or primary cilia in higher brain functions.

PMID- 24884635
TI  - Original surgical treatment of thoracolumbar subarachnoid cysts in six
      chondrodystrophic dogs.
AB  - BACKGROUND: Subarachnoid cysts are rare conditions in veterinary medicine,
      associated with spinal cord dysfunction. Most of the 100 cases of subarachnoid
      cysts described since the first report in 1968 were apparently not true cysts.
      Reported cysts are usually situated in the cervical area and occur in predisposed
      breeds such as the Rottweiler. The purpose of this retrospective study, from May
      2003 to April 2012, was to describe the distinctive features of thoracolumbar
      spinal subarachnoid cysts, together with their surgical treatment and outcome in
      6 chondrodystrophic dogs. RESULTS: Five Pugs and 1 French Bulldog were examined.
      Images suggestive of a subarachnoid cyst were obtained by myelography (2/6) and
      computed tomography myelography (4/6), and associated disc herniation was
      observed in 3/6 dogs. A hemilaminectomy was performed. The protruding disc
      eventually found in 5/6 dogs was treated by lateral corpectomy. The ventral
      leptomeningeal adhesions observed in all dogs after durotomy were dissected. No
      or only mild post-operative neurological degradation was observed. Follow-up
      studies (7 months to 4 years) indicated good outcome and no recurrence.
      CONCLUSIONS: All the thoracolumbar subarachnoid cysts described in these 6
      chondrodystrophic dogs were associated with leptomeningeal adhesions. Good
      results seemed to be obtained by dissecting and removing these adhesions. A
      protruding disc, found here in 5/6 dogs, needs to be ruled out and can be treated
      by lateral corpectomy.

PMID- 24884634
TI  - What have we learned about communication inequalities during the H1N1 pandemic: a
      systematic review of the literature.
AB  - BACKGROUND: During public health emergencies, public officials are busy in
      developing communication strategies to protect the population from existing or
      potential threats. However, a population's social and individual determinants
      (i.e. education, income, race/ethnicity) may lead to inequalities in individual
      or group-specific exposure to public health communication messages, and in the
      capacity to access, process, and act upon the information received by specific
      sub-groups- a concept defined as communication inequalities.The aims of this
      literature review are to: 1) characterize the scientific literature that examined
      issues related to communication to the public during the H1N1 pandemic, and 2)
      summarize the knowledge gained in our understanding of social determinants and
      their association with communication inequalities in the preparedness and
      response to an influenza pandemic. METHODS: Articles were searched in eight major
      communication, social sciences, and health and medical databases of scientific
      literature and reviewed by two independent reviewers by following the PRISMA
      guidelines. The selected articles were classified and analyzed in accordance with
      the Structural Influence Model of Public Health Emergency Preparedness
      Communications. RESULTS: A total of 118 empirical studies were included for final
      review. Among them, 78% were population-based studies and 22% were articles that
      employed information environment analyses techniques. Consistent results were
      reported on the association between social determinants of communication
      inequalities and emergency preparedness outcomes. Trust in public officials and
      source of information, worry and levels of knowledge about the disease, and
      routine media exposure as well as information-seeking behaviors, were related to
      greater likelihood of adoption of recommended infection prevention practices.
      When addressed in communication interventions, these factors can increase the
      effectiveness of the response to pandemics. CONCLUSIONS: Consistently across
      studies, a number of potential predictors of behavioral compliance to preventive
      recommendations during a pandemic were identified. Our findings show the need to
      include such evidence found in the development of future communication campaigns
      to ensure the highest rates of compliance with recommended protection measures
      and reduce communication inequalities during future emergencies.

PMID- 24884636
TI  - Induction of proline-rich tyrosine kinase 2 activation-mediated C6 glioma cell
      invasion after anti-vascular endothelial growth factor therapy.
AB  - BACKGROUND: Anti-angiogenic therapy inhibits tumor growth and is considered as a
      potential clinical therapy for malignant glioma. However, inevitable recurrences
      and unexpected tumor resistance, particularly increased invasion ability of
      glioma cell, were observed after anti-angiogenic treatment. The underlying
      mechanism remains undetermined. Focal adhesion kinase (FAK) and proline-rich
      tyrosine kinase 2 (Pyk2) are closely associated with cell migration; therefore,
      we investigated the possible role of these kinases in rat C6 glioma cell invasion
      induced by bevacizumab, a recombinant monoclonal antibody against vascular
      endothelial growth factor (VEGF). METHODS: The effects of bevacizumab on
      migration and invasion of C6 glioma cells were investigated in vitro and in vivo.
      The cells proliferation, migration, and invasion were determined by MTT assay,
      wound healing, and transwell assay, respectively. Invasive potential of glioma
      cells in vivo was assessed by counting vimentin-positive cells crossing the solid
      tumor rim by immunohistochemical staining. The total and phosphorylated protein
      levels of FAK and Pyk2 were detected by Western blotting. RESULTS: Bevacizumab
      exposure increased migration and invasion of cultured C6 cells in a concentration
      dependent manner. In addition, the continuous bevacizumab treatment also promoted
      tumor invasion in rat C6 intracranial glioma models. Bevacizumab treatment
      enhanced Pyk2 phosphorylation at Tyr402, but no effect on FAK phosphorylation at
      Tyr397 both in vitro and in vivo. Knockdown of Pyk2 by siRNA or inhibition of
      Pyk2 phosphorylation by Src kinase specific inhibitor PP1 partially inhibited
      bevacizumab-induced cell invasion in cultured C6 glioma cells. Furthermore, the
      combined administration of bevacizumab and PP1 significantly suppressed glioma
      cell invasion into surrounding brain tissues compared to bevacizumab treatment
      alone in experimental rats. CONCLUSIONS: These results suggest that anti-VEGF
      treatment promotes glioma cell invasion via activation of Pyk2. Inhibition of
      Pyk2 phosphorylation might be a potential target to ameliorate the therapeutic
      efficiency of anti-VEGF treatment.

PMID- 24884637
TI  - Statistical mechanics of the denatured state of a protein using replica-averaged
      metadynamics.
AB  - The characterization of denatured states of proteins is challenging because the
      lack of permanent structure in these states makes it difficult to apply to them
      standard methods of structural biology. In this work we use all-atom replica
      averaged metadynamics (RAM) simulations with NMR chemical shift restraints to
      determine an ensemble of structures representing an acid-denatured state of the
      86-residue protein ACBP. This approach has enabled us to reach convergence in the
      free energy landscape calculations, obtaining an ensemble of structures in
      relatively accurate agreement with independent experimental data used for
      validation. By observing at atomistic resolution the transient formation of
      native and non-native structures in this acid-denatured state of ACBP, we
      rationalize the effects of single-point mutations on the folding rate, stability,
      and transition-state structures of this protein, thus characterizing the role of
      the unfolded state in determining the folding process. 

PMID- 24884638
TI  - Prevalence and extent of infarct and microvascular obstruction following
      different reperfusion therapies in ST-elevation myocardial infarction.
AB  - BACKGROUND: Microvascular obstruction (MVO) describes suboptimal tissue perfusion
      despite restoration of infarct-related artery flow. There are scarce data on
      Infarct Size (IS) and MVO in relation to the mode and timing of reperfusion. We
      sought to characterise the prevalence and extent of microvascular injury and IS
      using Cardiovascular magnetic resonance (CMR), in relation to the mode of
      reperfusion following acute ST-Elevation Myocardial Infarction (STEMI). METHODS:
      CMR infarct characteristics were measured in 94 STEMI patients (age 61.0 +/- 13.1
      years) at 1.5 T. Seventy-three received reperfusion therapy: primary percutaneous
      coronary-intervention (PPCI, n = 47); thrombolysis (n = 12); rescue PCI (R-PCI, n
      = 8), late PCI (n = 6). Twenty-one patients presented late (>12 hours) and did
      not receive reperfusion therapy. RESULTS: IS was smaller in PPCI (19.8 +/- 13.2%
      of LV mass) and thrombolysis (15.2 +/- 10.1%) groups compared to patients in the
      late PCI (40.0 +/- 15.6%) and R-PCI (34.2 +/- 18.9%) groups, p <0.001. The
      prevalence of MVO was similar across all groups and was seen at least as
      frequently in the non-reperfused group (15/21, [76%] v 33/59, [56%], p = 0.21)
      and to a similar magnitude (1.3 (0.0-2.8) v 0.4 [0.0-2.9]% LV mass, p = 0.36)
      compared to patients receiving early reperfusion therapy. In the 73 reperfused
      patients, time to reperfusion, ischaemia area at risk and TIMI grade post-PCI
      were the strongest independent predictors of IS and MVO. CONCLUSIONS: In patients
      with acute STEMI, CMR-measured MVO is not exclusive to reperfusion therapy and is
      primarily related to ischaemic time. This finding has important implications for
      clinical trials that use CMR to assess the efficacy of therapies to reduce
      reperfusion injury in STEMI.

PMID- 24884639
TI  - Deprivation, clubs and drugs: results of a UK regional population-based cross
      sectional study of weight management strategies.
AB  - BACKGROUND: Despite rising levels of obesity in England, little is known about
      slimming club and weight loss drug (medication) use or users. In order to inform
      future commissioning, we report the prevalence of various weight management
      strategies and examine the associations between slimming club and medication use
      and age, gender, deprivation and body mass index. METHODS: A population based
      cross-sectional survey of 26,113 adults was conducted in South Yorkshire using a
      self-completed health questionnaire. Participants were asked whether they had
      ever used the following interventions to manage their weight: increasing
      exercise, healthy eating, controlling portion size, slimming club, over the
      counter weight loss medication, or meal replacements. Factors associated with
      slimming club and weight-loss medication use were explored using logistic
      regression. RESULTS: Over half of the sample was either overweight (36.6%) or
      obese (19.6%). Obesity was more common in the most deprived areas compared to the
      least deprived (26.3% vs. 12.0%). Healthy eating (49.0%), controlling portion
      size (43.4%), and increasing exercise (43.0%) were the most commonly reported
      weight management strategies. Less common strategies were attending a slimming
      club (17.2%), meal replacements (3.4%) and weight-loss medication (3.2%).
      Adjusting for BMI, age, deprivation and long standing health conditions, women
      were significantly more likely to report ever using a slimming club (adjusted OR
      = 18.63, 95% CI = 16.52-21.00) and more likely to report ever using over the
      counter weight-loss medications (AOR = 3.73, 95% CI = 3.10-4.48), while
      respondents from the most deprived areas were less likely to report using
      slimming clubs (AOR = 0.60, 95% CI = 0.53-0.68), and more likely to reporting
      using weight loss medications (AOR =1.38, 95% CI = 1.05-1.82). CONCLUSION: A
      large proportion of individuals report having used weight management strategies.
      Slimming clubs and over-the-counter weight loss medication account for a smaller
      proportion of the overall uptake. Those from less deprived areas were more likely
      to use slimming clubs while those from more deprived areas were more likely to
      use weight-loss medications. Future NHS and Local Authority commissioning of
      weight management services must be aware of this varying social gradient in
      weight management strategies.

PMID- 24884641
TI  - Expanded program of immunization coverage and associated factors among children
      age 12-23 months in Arba Minch town and Zuria District, Southern Ethiopia, 2013.
AB  - BACKGROUND: Immunization averts an estimated 2 to 3 million deaths every year
      globally. In Ethiopia only quarter of children are fully immunized; the rest are
      remained at risk for vaccine-preventable mortality. To increase the immunization,
      its coverage and predictors has to be identified. This study has measured
      immunization coverage and identified the predictors. METHODS: Cross-sectional
      community based study has been conducted within 630 age 12-23 months children in
      15 districts of Arba Minch town and Arba Minch Zuria district, Southern Ethiopia
      in March 2013. Census was done to identify eligible children. The 2005 world
      health organization expanded program of immunization cluster sampling method has
      been used. Data were collected using semi-structured pretested Amharic version
      questionnaire by interviewing index children's mothers/caretakers, copying from
      vaccine card and observing BCG vaccine scar. Data were processed using SPSS
      version 16. Associations between dependent and independent variables has been
      assessed and presented using three consecutive logistic regression models.
      RESULT: Nearly three fourth (73.2%) of children in Arba Minch Town and Arba Minch
      Zuria district were fully immunized. The rest 20.3% were partially immunized and
      6.5% received no vaccine. Mother education, mothers' perception to accessibility
      of vaccines, mothers' knowledge to vaccine schedule of their site, place of
      delivery and living altitude were independent predictors of children immunization
      status. CONCLUSION: Expanded program of immunization (EPI) coverage at Arba Minch
      town and Arba Minch Zuria district is better than the national immunization
      coverage but still below the goal. Educating mother, promoting institution
      delivery could help to maintain and enhance current immunization coverage. More
      emphasis should be given to the highland areas of the area.

PMID- 24884640
TI  - Impact of recurrent gene duplication on adaptation of plant genomes.
AB  - BACKGROUND: Recurrent gene duplication and retention played an important role in
      angiosperm genome evolution. It has been hypothesized that these processes
      contribute significantly to plant adaptation but so far this hypothesis has not
      been tested at the genome scale. RESULTS: We studied available sequenced
      angiosperm genomes to assess the frequency of positive selection footprints in
      lineage specific expanded (LSE) gene families compared to single-copy genes using
      a dN/dS-based test in a phylogenetic framework. We found 5.38% of alignments in
      LSE genes with codons under positive selection. In contrast, we found no evidence
      for codons under positive selection in the single-copy reference set. An analysis
      at the branch level shows that purifying selection acted more strongly on single
      copy genes than on LSE gene clusters. Moreover we detect significantly more
      branches indicating evolution under positive selection and/or relaxed constraint
      in LSE genes than in single-copy genes. CONCLUSIONS: In this - to our knowledge 
      first genome-scale study we provide strong empirical support for the hypothesis
      that LSE genes fuel adaptation in angiosperms. Our conservative approach for
      detecting selection footprints as well as our results can be of interest for
      further studies on (plant) gene family evolution.

PMID- 24884642
TI  - Risk stratification in emergency patients by copeptin.
AB  - BACKGROUND: Rapid risk stratification is a core task in emergency medicine.
      Identifying patients at high and low risk shortly after admission could help
      clinical decision-making regarding treatment, level of observation, allocation of
      resources and post discharge follow-up. The purpose of the present study was to
      determine short-, mid- and long-term mortality by plasma measurement of copeptin
      in unselected admitted patients. METHOD: Consecutive patients >40-years-old
      admitted to an inner-city hospital were included. Within the first 24 hours after
      admission, a structured medical interview was conducted and self-reported medical
      history was recorded. All patients underwent a clinical examination, an
      echocardiographic evaluation and collection of blood for later measurement of
      risk markers. RESULTS: Plasma for copeptin measurement was available from 1,320
      patients (average age 70.5 years, 59.4% women). Median follow-up time was 11.5
      years (range 11.0 to 12.0 years). Copeptin was elevated (that is, above the 97.5
      percentile in healthy individuals).Mortality within the first week was 2.7%
      (17/627) for patients with elevated copeptin (above the 97.5 percentile, that is,
      >11.3 pmol/L) compared to 0.1% (1/693) for patients with normal copeptin
      concentrations (that is, <=11.3 pmol/L) (P <0.01). Three-month mortality was
      14.5% (91/627) for patients with elevated copeptin compared to 3.2% (22/693) for
      patients with normal copeptin. Similar figures for one-year mortality and for the
      entire observation period were 27.6% (173/627) versus 8.7% (60/693) and 82.9%
      (520/527) versus 57.5% (398/693) (P <0.01 for both), respectively.Using
      multivariable Cox regression analyses shows that elevated copeptin was
      significantly and independently related to short-, mid- and long-term mortality.
      Adjusted hazard ratios were 2.4 for three-month mortality, 1.9 for one-year
      mortality and 1.4 for mortality in the entire observation period. CONCLUSIONS: In
      patients admitted to an inner-city hospital, copeptin was strongly associated
      with short-, mid- and long-term mortality. The results suggest that rapid
      copeptin measurement could be a useful tool for both disposition in an emergency
      department and for mid- and long-term risk assessment.

PMID- 24884643
TI  - A phase IotaI study of five peptides combination with oxaliplatin-based
      chemotherapy as a first-line therapy for advanced colorectal cancer (FXV study).
AB  - BACKGROUND: We previously conducted a phase I trial for advanced colorectal
      cancer (CRC) using five HLA-A*2402-restricted peptides, three derived from
      oncoantigens and two from vascular endothelial growth factor (VEGF) receptors,
      and confirmed safety and immunological responses. To evaluate clinical benefits
      of cancer vaccination treatment, we conducted a phase II trial using the same
      peptides in combination with oxaliplatin-based chemotherapy as a first-line
      therapy. METHODS: The primary objective of the study was the response rates (RR).
      Progression free survival (PFS), overall survival (OS), and immunological
      parameters were evaluated as secondary objective. The planned sample size was
      more than 40 patients for both HLA2402-matched and -unmatched groups. All
      patients received a cocktail of five peptides (3 mg each) mixed with 1.5 ml of
      IFA which was subcutaneously administered weekly for the first 12 weeks followed
      by biweekly administration. Presence or absence of the HLA-A*2402 genotype were
      used for classification of patients into two groups. RESULTS: Between February
      2009 and November 2012, ninety-six chemotherapy naive CRC patients were enrolled
      under the masking of their HLA-A status. Ninety-three patients received mFOLFOX6
      and three received XELOX. Bevacizumab was added in five patients. RR was 62.0%
      and 60.9% in the HLA-A*2402-matched and -unmatched groups, respectively
      (p=0.910). The median OS was 20.7 months in the HLA-A*2402-matched group and 24.0
      months in the unmatched group (log-rank, p=0.489). In subgroup with a
      neutrophil/lymphocyte ratio (NLR) of <3.0, patients in the HLA-matched group did
      not survive significantly longer than those in the unmatched group (log-rank,
      p=0.289) but showed a delayed response. CONCLUSIONS: Although no significance was
      observed for planned statistical efficacy endpoints, a delayed response was
      observed in subgroup with a NLR of <3.0. Biomarkers such as NLR might be useful
      for selecting patients with a better treatment outcome by the vaccination. TRIAL
      REGISTRATION: Trial registration: UMIN000001791.

PMID- 24884644
TI  - Calpain: a molecule to induce AIF-mediated necroptosis in RGC-5 following
      elevated hydrostatic pressure.
AB  - BACKGROUND: RIP3 (Receptor-interacting protein 3) pathway was mainly described as
      the molecular mechanism of necroptosis (programmed necrosis). But recently, non
      RIP3 pathways were found to mediate necroptosis. We deliberate to investigate the
      effect of calpain, a molecule to induce necroptosis as reported (Cell Death
      Differ 19:245-256, 2012), in RGC-5 following elevated hydrostatic pressure.
      RESULTS: First, we identified the existence of necroptosis of RGC-5 after insult
      by using necrostatin-1 (Nec-1, necroptosis inhibitor) detected by flow cytometry.
      Immunofluorescence staining and western blot were used to detect the expression
      of calpain. Western blot analysis was carried out to describe the truncated AIF
      (tAIF) expression with or without pretreatment of ALLN (calpain activity
      inhibitor). Following elevated hydrostatic pressure, necroptotic cells pretreated
      with or without ALLN was stained by Annexin V/PI, The activity of calpain was
      also examined to confirm the inhibition effect of ALLN. The results showed that
      after cell injury there was an upregulation of calpain expression. Upon adding
      ALLN, the calpain activity was inhibited, and tAIF production was reduced upon
      injury along with the decreased number of necroptosis cells. CONCLUSION: Our
      study found that calpain may induce necroptosis via tAIF-modulation in RGC-5
      following elevated hydrostatic pressure.

PMID- 24884645
TI  - Setting policy priorities to address eating disorders and weight stigma: views
      from the field of eating disorders and the US general public.
AB  - BACKGROUND: The prevalence and health consequences of eating disorders and weight
      stigmatization have prompted increasing discussion of potential policy actions to
      address these public health issues. The present study aimed to assess support for
      policy strategies to address eating disorders and weight stigmatization among the
      general public and relevant health professionals. METHODS: An Internet survey was
      fielded to a national sample of 944 US adults and 1,420 members of professional
      organizations specializing in eating disorders to examine their support for 23
      potential policy strategies to address eating disorders and weight stigma.
      Participants also rated policy actions according to their potential for positive
      impact and feasible implementation. RESULTS: Support for the majority of health
      and social policies was high in both samples. For example, strategies to 1)
      improve school-based health curriculum to include content aimed at preventing
      eating disorders, 2) require training for educators and health providers on the
      prevention and early identification of eating disorders, and 3) implement school
      based anti-bullying policies that that protect students from being bullied about
      their weight, were supported by over two-thirds of participants. CONCLUSIONS: Our
      findings suggest that both health and social policy actions will be important in
      broader policy initiatives to address eating disorders and weight stigma.

PMID- 24884646
TI  - Time-based loss in visual short-term memory is from trace decay, not temporal
      distinctiveness.
AB  - There is no consensus as to why forgetting occurs in short-term memory tasks. In
      past work, we have shown that forgetting occurs with the passage of time, but
      there are 2 classes of theories that can explain this effect. In the present
      work, we investigate the reason for time-based forgetting by contrasting the
      predictions of temporal distinctiveness and trace decay in the procedure in which
      we have observed such loss, involving memory for arrays of characters or letters
      across several seconds. The 1st theory, temporal distinctiveness, predicts that
      increasing the amount of time between trials will lead to less proactive
      interference, resulting in less forgetting across a retention interval. In the
      2nd theory, trace decay, temporal distinctiveness between trials is irrelevant to
      the loss over a retention interval. Using visual array change detection tasks in
      4 experiments, we find small proactive interference effects on performance under
      some specific conditions, but no concomitant change in the effect of a retention
      interval. We conclude that trace decay is the more suitable class of explanations
      of the time-based forgetting in short-term memory that we have observed, and we
      suggest the need for further clarity in what the exact basis of that decay may
      be.

PMID- 24884647
TI  - Discrete-state and continuous models of recognition memory: testing core
      properties under minimal assumptions.
AB  - A classic discussion in the recognition-memory literature concerns the question
      of whether recognition judgments are better described by continuous or discrete
      processes. These two hypotheses are instantiated by the signal detection theory
      model (SDT) and the 2-high-threshold model, respectively. Their comparison has
      almost invariably relied on receiver operating characteristic data. A new model
      comparison approach based on ranking judgments is proposed here. This approach
      has several advantages: It does not rely on particular distributional assumptions
      for the models, and it does not require costly experimental manipulations. These
      features permit the comparison of the models by means of simple paired-comparison
      tests instead of goodness-of-fit results and complex model-selection methods that
      are predicated on many auxiliary assumptions. Empirical results from 2
      experiments are consistent with a continuous memory process such as the one
      assumed by SDT.

PMID- 24884648
TI  - Eliminating the Simon effect by instruction.
AB  - A growing body of research demonstrates that instructions can elicit automatic
      response activations. The results of the present study indicate that instruction
      based response activations can also counteract automatic response activations
      based on long-term associations. To this end, we focused on the Simon effect,
      which is the observation that responding to a nonspatial feature of a stimulus
      (e.g., color) is faster and more accurate when the task-irrelevant stimulus
      position matches the spatial position of the correct response. The Simon effect
      can be eliminated or even reversed when combining a Simon task with an
      incompatible position task (e.g., press right for left stimuli; press left for
      right stimuli). The present study demonstrates that the Simon effect is
      eliminated even after presenting only the instructions of an incompatible
      position task, without participants having the opportunity to practice that task.
      Moderate practice of the incompatible task did not add anything to the effect of
      the instructions. Finally, the instructions of a compatible spatial stimulus
      response task did not affect the Simon effect. The present results converge with
      previous findings indicating that the Simon effect is highly malleable and
      suggest that stimulus-response associations formed on the basis of instructions
      can counteract effects of long-term stimulus-response associations.

PMID- 24884649
TI  - The role of the verb in grammatical function assignment in English and Korean.
AB  - One of the central questions in speech production is how speakers decide which
      entity to assign to which grammatical function. According to the lexical
      hypothesis (e.g., Bock & Levelt, 1994), verbs play a key role in this process
      (e.g., "send" and "receive" result in different entities being assigned to the
      subject position). In contrast, according to the structural hypothesis (e.g.,
      Bock, Irwin, & Davidson, 2004), grammatical functions can be assigned based on a
      speaker's conceptual representation of an event, even before a particular verb is
      chosen. In order to examine the role of the verb in grammatical function
      assignment, we investigated whether English and Korean speakers exhibit semantic
      interference effects for verbs during a scene description task. We also analyzed
      speakers' eye movements during production. We found that English speakers
      exhibited verb interference effects and also fixated the action/verb region
      before the subject region. In contrast, Korean speakers did not show any verb
      interference effects and did not fixate the action/verb region before the subject
      region. Rather, in Korean, looks to the action/verb region sharply increased
      following looks to the object region. The findings provide evidence for the
      lexical hypothesis for English and are compatible with the structural hypothesis
      for Korean. We suggest that whether the verb is retrieved before speech onset
      depends on the role that the verb plays in grammatical function assignment or
      structural choice in a particular language.

PMID- 24884650
TI  - The discriminant power of RNA features for pre-miRNA recognition.
AB  - BACKGROUND: Computational discovery of microRNAs (miRNA) is based on pre
      determined sets of features from miRNA precursors (pre-miRNA). Some feature sets
      are composed of sequence-structure patterns commonly found in pre-miRNAs, while
      others are a combination of more sophisticated RNA features. In this work, we
      analyze the discriminant power of seven feature sets, which are used in six pre
      miRNA prediction tools. The analysis is based on the classification performance
      achieved with these feature sets for the training algorithms used in these tools.
      We also evaluate feature discrimination through the F-score and feature
      importance in the induction of random forests. RESULTS: Small or non-significant
      differences were found among the estimated classification performances of
      classifiers induced using sets with diversification of features, despite the wide
      differences in their dimension. Inspired in these results, we obtained a lower
      dimensional feature set, which achieved a sensitivity of 90% and a specificity of
      95%. These estimates are within 0.1% of the maximal values obtained with any
      feature set (SELECT, Section "Results and discussion") while it is 34 times
      faster to compute. Even compared to another feature set (FS2, see Section
      "Results and discussion"), which is the computationally least expensive feature
      set of those from the literature which perform within 0.1% of the maximal values,
      it is 34 times faster to compute. The results obtained by the tools used as
      references in the experiments carried out showed that five out of these six tools
      have lower sensitivity or specificity. CONCLUSION: In miRNA discovery the number
      of putative miRNA loci is in the order of millions. Analysis of putative pre
      miRNAs using a computationally expensive feature set would be wasteful or even
      unfeasible for large genomes. In this work, we propose a relatively inexpensive
      feature set and explore most of the learning aspects implemented in current ab
      initio pre-miRNA prediction tools, which may lead to the development of efficient
      ab-initio pre-miRNA discovery tools.The material to reproduce the main results
      from this paper can be downloaded from
      http://bioinformatics.rutgers.edu/Static/Software/discriminant.tar.gz.

PMID- 24884651
TI  - The effects of increased therapy time on cognition and mood in frail patients
      with a stroke who rehabilitate on rehabilitation units of nursing homes in the
      Netherlands: a protocol of a comparative study.
AB  - BACKGROUND: Recovery after stroke is dependent on how much time can be spent on
      rehabilitation. Recently, we found that therapy time for older stroke patients on
      a rehabilitation unit of a nursing home could be increased significantly from 8.6
      to at least 13 hours a week. This increase was attained by the implementation of
      interventions, focused on strength, mobility and balance. Nurses carried out
      these exercises with the patients during their daily activities. The aim of the
      present study is to investigate if increased therapy time has a positive effect
      on cognition, mood (depression and anxiety), and ADL in stroke patients. METHODS:
      A comparative single blind controlled study will be applied. Patients suffering
      from a stroke and staying on one of the rehabilitation units of the nursing homes
      are eligible for participation. Participants belong to the intervention group if
      they stay in two nursing homes where four interventions of the Clinical Nursing
      Rehabilitation Stroke Guideline were implemented. Participants who stay in two
      nursing homes where therapy is given according to the Dutch stroke Guideline, are
      included in the control group. Clinical neuropsychologists will assess patients'
      cognitive functioning, level of depression (mood) and anxiety. Nurses will assess
      a Barthel Index score on a weekly basis (ADL). These variables are measured at
      baseline, after 8 weeks and at the moment when participants are discharged from
      the nursing home. DISCUSSION: The present study evaluates the effect of increased
      therapy time on cognition, mood (level of depression and anxiety), and ADL in
      stroke patients. When positive effects will be found this study can guide policy
      makers and practitioners on how to implement more therapy time on rehabilitation
      wards of nursing homes. TRIAL REGISTRATION: TNR Our study has been documented in
      the Dutch Trial Registration, TC = 3871.

PMID- 24884653
TI  - Correlates of stunting among children in Ghana.
AB  - BACKGROUND: Stunting, is a linear growth retardation, which results from
      inadequate intake of food over a long period of time that may be worsened by
      chronic illness. Over a long period of time, inadequate nutrition or its effects
      could result in stunting. This paper examines the correlates of stunting among
      children in Ghana using data from the 2008 Ghana Demographic and Health Survey
      (GDHS). METHODS: The paper uses data from the children recode file of the 2008
      Demographic and Health Survey (DHS), a nationally representative cross sectional
      survey conducted in Ghana. A total of 2379 children under five years who had
      valid anthropometric data were used for the study. Data on the stunting of
      children were collected by measuring the height of all children under six years
      of age. A measuring board produced by Shorr Productions was used to obtain the
      height of the children. Children under 2 years of age were measured lying down on
      the board while those above 2 years were measured standing. In the DHS data, a z
      score is given for the child's height relative to the age. Both bi-variate and
      multi-variate statistics are used to examine the correlates of stunting. RESULTS:
      Stunting was common among males than females. Age of child was a significant
      determinant of stunting with the highest odd of stunting been among children aged
      36-47 months. Region was significantly related to stunting. Children from the
      Eastern Region were more likely to be stunted than children from the Western
      Region which is the reference group (OR = 1.7 at p < 0.05). Number of children in
      household was significantly related to stunting. Children in households with 5-8
      children were 1.3 times more likely to be stunted compared to those with 1-4
      children (p < .05). Mother's age was a significant predictor of stunting with
      children whose mothers were aged 35-44 years being more likely to be stunted.
      CONCLUSION: Culturally appropriate interventions and policies should be put in
      place to minimise the effects of the distal, proximal and intermediate factors on
      stunting among under 5 children in Ghana.

PMID- 24884652
TI  - The relation of sexual function to migraine-related disability, depression and
      anxiety in patients with migraine.
AB  - BACKGROUND: Depression and anxiety are two phenomena that affect quality of life
      as well as sexual function. Depression and anxiety levels are reported to be high
      in migraine sufferers. We aimed to understand whether sexual function in women
      with migraine was associated to migraine-related disability and frequency of
      migraine attacks, and whether this relationship was modulated by depressive and
      anxiety symptoms. METHODS: As migraine is more commonly seen in females, a total
      of 50 women with migraine were included. The diagnosis of migraine with or
      without aura was confirmed by two specialists in Neurology, according to the
      second edition of International Headache Society (IHS) International
      Classification of Headache Disorders (ICHD-II) in 2004. Migraine disability
      assessment scale score, female sexual function index scores, Beck depression
      inventory score and Beck anxiety inventory scores. RESULTS: Mean MIDAS score was
      19.3 +/- 12.8, and mean number of migraine attacks per month were 4.3 +/- 2.7.
      Mean Female Sexual Function Index score was 20.9 +/- 5.9 and 90% of patients had
      sexual dysfunction. Sexual dysfunction was not related to MIDAS score or
      frequency and severity of attacks. No relationship between sexual function and
      anxiety was found, whereas severity of depressive symptoms was closely related to
      sexual function. Depressive symptoms affected all dimensions of sexual function,
      except for pain. CONCLUSION: Sexual dysfunction seemed to be very common in our
      patients with migraine, while not related to migraine related disability,
      frequency of attacks and migraine severity or anxiety. The most important factor
      that predicted sexual function was depression, which was also independent of
      disease severity and migraine related disability. While future larger scale
      studies are needed to clarify the exact relationship, depressive and sexual
      problems should be properly addressed in all patients with migraine, regardless
      of disease severity or disability.

PMID- 24884654
TI  - Molecular characterization of the SPL gene family in Populus trichocarpa.
AB  - BACKGROUND: SPLs, a family of transcription factors specific to plants, play
      vital roles in plant growth and development through regulation of various
      physiological and biochemical processes. Although Populus trichocarpa is a model
      forest tree, the PtSPL gene family has not been systematically studied. RESULTS:
      Here we report the identification of 28 full-length PtSPLs, which distribute on
      14 P. trichocarpa chromosomes. Based on the phylogenetic relationships of SPLs in
      P. trichocarpa and Arabidopsis, plant SPLs can be classified into 6 groups. Each
      group contains at least a PtSPL and an AtSPL. The N-terminal zinc finger 1 (Zn1)
      of SBP domain in group 6 SPLs has four cysteine residues (CCCC-type), while Zn1
      of SPLs in the other groups mainly contains three cysteine and one histidine
      residues (C2HC-type). Comparative analyses of gene structures, conserved motifs
      and expression patterns of PtSPLs and AtSPLs revealed the conservation of plant
      SPLs within a group, whereas among groups, the P. trichocarpa and Arabidopsis
      SPLs were significantly different. Various conserved motifs were identified in
      PtSPLs but not found in AtSPLs, suggesting the diversity of plant SPLs. A total
      of 11 pairs of intrachromosome-duplicated PtSPLs were identified, suggesting the
      importance of gene duplication in SPL gene expansion in P. trichocarpa. In
      addition, 18 of the 28 PtSPLs, belonging to G1, G2 and G5, were found to be
      targets of miR156. Consistently, all of the AtSPLs in these groups are regulated
      by miR156. It suggests the conservation of miR156-mediated posttranscriptional
      regulation in plants. CONCLUSIONS: A total of 28 full-length SPLs were identified
      from the whole genome sequence of P. trichocarpa. Through comprehensive analyses
      of gene structures, phylogenetic relationships, chromosomal locations, conserved
      motifs, expression patterns and miR156-mediated posttranscriptional regulation,
      the PtSPL gene family was characterized. Our results provide useful information
      for evolution and biological function of plant SPLs.

PMID- 24884655
TI  - CBD binding domain fused gamma-lactamase from Sulfolobus solfataricus is an
      efficient catalyst for (-) gamma-lactam production.
AB  - BACKGROUND: gamma-lactamase is used for the resolution of gamma-lactam which is
      utilized in the synthesizing of abacavir and peramivir. In some cases, enzymatic
      method is the most utilized method because of its high efficiency and
      productivity. The cellulose binding domain (CBD) of cellulose is often used as
      the bio-specific affinity matrix for enzyme immobilization. Cellulose is cheap
      and it has excellent chemical and physical properties. Meanwhile, binding between
      cellulose and CBD is tight and the desorption rarely happened. RESULTS: We
      prepared two fusion constructs of the gamma-lactamase gene gla, which was from
      Sulfolobus solfataricus P2. These two constructs had Cbd (cellulose binding
      domain from Clostridium thermocellum) fused at amino or carboxyl terminus of the
      gamma-lactamase. These two constructs were heterogeneously expressed in E. coli
      rosetta (DE3) as two fusion proteins. Both of them were immobilized well on
      Avicel (microcrystalline cellulose matrix). The apparent kinetic parameters
      revealed that carboxyl terminus fused protein (Gla-linker-Cbd) was a better
      catalyst. The V(max) and k(cat) value of Avicel immobilized Gla-linker-Cbd were
      381 U mg-1 and 4.7 * 105 s-1 respectively. And the values of the free Gla-linker
      Cbd were 151 U mg-1 and 1.8 * 105 s-1 respectively. These data indicated that the
      catalytic efficiency of the enzyme was upgraded after immobilization. The
      immobilized Gla-linker-Cbd had a 10-degree temperature optimum dropping from 80
      degrees C to 70 degrees C but it was stable when incubated at 60 degrees C for 48
      h. It remained stable in catalyzing 20-batch reactions. After optimization, the
      immobilized enzyme concentration in transformation was set as 200 mg/mL. We found
      out that there was inhibition that occurred to the immobilized enzyme when
      substrate concentration exceeded 60 mM. Finally a 10 mL-volume transformation was
      conducted, in which 0.6 M substrate was hydrolyzed and the resolution was
      completed within 9 h with a 99.5% ee value. CONCLUSIONS: Cellulose is the most
      abundant and renewable material on the Earth. The absorption between Cbd domain
      and cellulose is a bio-green process. The cellulose immobilized fusion Gla
      exhibited good catalytic characters, therefore we think the cellulose immobilized
      Gla is a promising catalyst for the industrial preparation of (-) - gamma-lactam.

PMID- 24884656
TI  - Determinants of exercise capacity in cystic fibrosis patients with mild-to
      moderate lung disease.
AB  - BACKGROUND: Adult patients with cystic fibrosis (CF) frequently have reduced
      exercise tolerance, which is multifactorial but mainly due to bronchial
      obstruction. The aim of this retrospective analysis was to determine the
      mechanisms responsible for exercise intolerance in patients with mild-to-moderate
      or severe disease. METHODS: Cardiopulmonary exercise testing with blood gas
      analysis at peak exercise was performed in 102 patients aged 28 +/- 11 years: 48
      patients had severe lung disease (FEV1 < 50%, group 1) and 54 had mild-to
      moderate lung disease (FEV1 >= 50%, group 2). VO2 peak was measured and
      correlated with clinical, biological, and functional parameters. RESULTS: VO2
      peak for all patients was 25 +/- 9 mL/kg/min (65 +/- 21% of the predicted value)
      and was < 84% of predicted in 82% of patients (100% of group 1, 65% of group 2).
      VO2 peak was correlated with body mass index, C-reactive protein, FEV1, FVC, RV,
      DLCO, VE/VCO2 peak, VD/VT, PaO2, PaCO2, P(A-a)O2, and breathing reserve. In
      multivariate analysis, FEV1 and overall hyperventilation during exercise were
      independent determinants of exercise capacity (R(2) = 0.67). FEV1 was the major
      significant predictor of VO2 peak impairment in group 1, accounting for 31% of
      VO2 peak alteration, whereas excessive overall hyperventilation (reduced or
      absent breathing reserve and VE/VCO2) accounted for 41% of VO2 alteration in
      group 2. CONCLUSION: Exercise limitation in adult patients with CF is largely
      dependent on FEV1 in patients with severe lung disease and on the magnitude of
      the ventilatory response to exercise in patients with mild-to-moderate lung
      disease.

PMID- 24884657
TI  - Characterization of a new mouse p53 variant: loss-of-function and gain-of
      function.
AB  - BACKGROUND: p53 is a major tumor suppressor that is inactivated in over 50% of
      human cancer types through either mutation or inactivating interactions with
      viral or cellular proteins. The uncertainties around the link between p53 status,
      therapeutic response, and outcome in cancer suggest that additional factors may
      be involved. p53 isoforms that are generated via the alternative splicing pathway
      may be promising candidates for further investigation. RESULT: In this study, we
      report one new p53 protein with two internally deleted regions, resulting in one
      deleted amino acid fragment (from amino acid residues 42 to 89) and one reading
      frame-shift region (from amino acid residues 90-120) compared to wild-type p53.
      The functional status of the new p53 protein, which has a defect in its proline
      rich and N-terminal DNA-binding domains, was characterized as possessing an
      intact conformation, exhibiting no transactivation activity, exerting a dominant
      negative effect and an interacting with a coactivator with an arginine
      methyltransferase activity. CONCLUSION: Taken together, our findings provide
      valuable information about the structure and function of p53 for the regulation
      of transactivation activity and cellular protein-protein interactions.
      Furthermore, natural p53 isoforms will help us understand the functional roles of
      the p53 family and potential therapeutics for p53-dependent cancers.

PMID- 24884658
TI  - Metformin-associated lactic acidosis presenting as an ischemic gut in a patient
      who then survived a cardiac arrest: a case report.
AB  - INTRODUCTION: Lactic acidosis is the most common cause of metabolic acidosis in
      hospitalized patients. It is recognized as a potential complication of metformin
      use, particularly in patients with risk factors such as renal dysfunction, liver
      disease, and heavy alcohol ingestion. These conditions are associated with
      systemic hypoxemia, which may be caused by cardiorespiratory disease, major
      surgery, sepsis, dehydration, old age, and overdose. The reported frequency of
      lactic acidosis is 0.06 per 1000 patient-years, mostly in patients with
      predisposing factors. This case is important because it details the seriousness
      of metformin-associated lactic acidosis in a critically ill patient and because,
      to the best of our knowledge, our patient survived with minimal residual defect
      despite experiencing a cardiac arrest. CASE PRESENTATION: A 66-year-old Caucasian
      woman presented to our hospital with profound lactic acidosis, which was
      initially thought to be ischemic gut. She then survived an in-hospital pulseless
      electrical activity arrest. CONCLUSION: Metformin-associated lactic acidosis is a
      diagnosis by exclusion; however, a high degree of clinical suspicion supplemented
      by prompt multisystem organ support can significantly influence the outcome in
      critically ill patients.

PMID- 24884659
TI  - Sulfur nanocrystals confined in carbon nanotube network as a binder-free
      electrode for high-performance lithium sulfur batteries.
AB  - A binder-free nano sulfur-carbon nanotube composite material featured by clusters
      of sulfur nanocrystals anchored across the superaligned carbon nanotube (SACNT)
      matrix is fabricated via a facile solution-based method. The conductive SACNT
      matrix not only avoids self-aggregation and ensures dispersive distribution of
      the sulfur nanocrystals but also offers three-dimensional continuous electron
      pathway, provides sufficient porosity in the matrix to benefit electrolyte
      infiltration, confines the sulfur/polysulfides, and accommodates the volume
      variations of sulfur during cycling. The nanosized sulfur particles shorten
      lithium ion diffusion path, and the confinement of sulfur particles in the SACNT
      network guarantees the stability of structure and electrochemical performance of
      the composite. The nano S-SACNT composite cathode delivers an initial discharge
      capacity of 1071 mAh g(-1), a peak capacity of 1088 mAh g(-1), and capacity
      retention of 85% after 100 cycles with high Coulombic efficiency (~100%) at 1 C.
      Moreover, at high current rates the nano S-SACNT composite displays impressive
      capacities of 1006 mAh g(-1) at 2 C, 960 mAh g(-1) at 5 C, and 879 mAh g(-1) at
      10 C.

PMID- 24884660
TI  - In silico modeling predicts drug sensitivity of patient-derived cancer cells.
AB  - BACKGROUND: Glioblastoma (GBM) is an aggressive disease associated with poor
      survival. It is essential to account for the complexity of GBM biology to improve
      diagnostic and therapeutic strategies. This complexity is best represented by the
      increasing amounts of profiling ("omics") data available due to advances in
      biotechnology. The challenge of integrating these vast genomic and proteomic data
      can be addressed by a comprehensive systems modeling approach. METHODS: Here, we
      present an in silico model, where we simulate GBM tumor cells using genomic
      profiling data. We use this in silico tumor model to predict responses of cancer
      cells to targeted drugs. Initially, we probed the results from a recent
      hypothesis-independent, empirical study by Garnett and co-workers that analyzed
      the sensitivity of hundreds of profiled cancer cell lines to 130 different
      anticancer agents. We then used the tumor model to predict sensitivity of patient
      derived GBM cell lines to different targeted therapeutic agents. RESULTS: Among
      the drug-mutation associations reported in the Garnett study, our in silico model
      accurately predicted ~85% of the associations. While testing the model in a
      prospective manner using simulations of patient-derived GBM cell lines, we
      compared our simulation predictions with experimental data using the same cells
      in vitro. This analysis yielded a ~75% agreement of in silico drug sensitivity
      with in vitro experimental findings. CONCLUSIONS: These results demonstrate a
      strong predictability of our simulation approach using the in silico tumor model
      presented here. Our ultimate goal is to use this model to stratify patients for
      clinical trials. By accurately predicting responses of cancer cells to targeted
      agents a priori, this in silico tumor model provides an innovative approach to
      personalizing therapy and promises to improve clinical management of cancer.

PMID- 24884661
TI  - Clinical factors affecting pathological fracture and healing of unicameral bone
      cysts.
AB  - BACKGROUND: Unicameral bone cyst (UBC) is the most common benign lytic bone
      lesion seen in children. The aim of this study is to investigate clinical factors
      affecting pathological fracture and healing of UBC. METHODS: We retrospectively
      reviewed 155 UBC patients who consulted Nagoya musculoskeletal oncology group
      hospitals in Japan. Sixty of the 155 patients had pathological fracture at
      presentation. Of 141 patients with follow-up periods exceeding 6 months, 77 were
      followed conservatively and 64 treated by surgery. RESULTS: The fracture risk was
      significantly higher in the humerus than other bones. In multivariate analysis,
      ballooning of bone, cyst in long bone, male sex, thin cortical thickness and
      multilocular cyst were significant adverse prognostic factors for pathological
      fractures at presentation. The healing rates were 30% and 83% with observation
      and surgery, respectively. Multivariate analysis revealed that fracture at
      presentation and history of biopsy were good prognostic factors for healing of
      UBC in patients under observation. CONCLUSION: The present results suggest that
      mechanical disruption of UBC such as fracture and biopsy promotes healing, and
      thus watchful waiting is indicated in these patients, whereas patients with poor
      prognostic factors for fractures should be considered for surgery.

PMID- 24884662
TI  - Upregulation of the tight junction protein occludin: effects on ventilation
      induced lung injury and mechanisms of action.
AB  - BACKGROUND: Occludin, a tight junction protein, plays an important role in
      maintaining the integrity of the lung epithelial barrier; however, its role in
      ventilation-induced lung injury has not been explored. Here, we measured the
      expression of occludin with different tidal volumes. Our study indicated that the
      level of occludin was significantly decreased and alveolar permeability was
      increased owing to acute lung injury. METHODS: Thirty healthy Wistar rats (15
      female, 15 male) weighing 250-300 g, were randomly divided into 5 groups (n = 6
      in each group): a control group (group C), a low tidal volume group (group L), a
      low tidal volume + protein kinase C(PKC) inhibitor group (group L + P), a high
      tidal volume group (group H) and a high tidal volume + PKC inhibitor group (group
      H + P). Tracheas of rats in the control group underwent incision without any
      special treatment. The other four groups were mechanically ventilated for 4 h.
      The rats in groups L + P and H + P were treated with a PKC inhibitor
      (bisindolylmaleimide I, 0.12 mg/kg) by intramuscular injection 1 h before
      anesthesia. Rats were sacrificed after mechanical ventilation. Specimens of lung
      tissues were harvested. Lung pathological changes were observed using an optical
      microscope, and lung wet/dry weight ratio was measured. The occludin protein
      level was assayed by immunohistochemistry and Western blotting. RESULTS: HE
      staining and immunohistochemistry results showed that occludin was mainly located
      in alveolar epithelial cells and some alveolar endothelial cells. The lung injury
      and alveolar edema were more serious in high tidal volume groups than in low
      tidal volume groups. Occludin expression was reduced and PKC activation was
      increased in rats in the high tidal volume groups compared with rats in the low
      tidal volume groups. Rats that were pretreated with the PKC inhibitor had less
      pulmonary edema induced by the high tidal volume ventilation. CONCLUSION:
      Mechanical ventilation can activate the PKC signaling pathway and tight junction
      proteins participate in this pathway. Up-regulation of occludin can reduce
      ventilation-induced lung injury.

PMID- 24884663
TI  - MOIRAI: a compact workflow system for CAGE analysis.
AB  - BACKGROUND: Cap analysis of gene expression (CAGE) is a sequencing based
      technology to capture the 5' ends of RNAs in a biological sample. After mapping,
      a CAGE peak on the genome indicates the position of an active transcriptional
      start site (TSS) and the number of reads correspond to its expression level. CAGE
      is prominently used in both the FANTOM and ENCODE project but presently there is
      no software package to perform the essential data processing steps. RESULTS: Here
      we describe MOIRAI, a compact yet flexible workflow system designed to carry out
      the main steps in data processing and analysis of CAGE data. MOIRAI has a
      graphical interface allowing wet-lab researchers to create, modify and run
      analysis workflows. Embedded within the workflows are graphical quality control
      indicators allowing users assess data quality and to quickly spot potential
      problems. We will describe three main workflows allowing users to map, annotate
      and perform an expression analysis over multiple samples. CONCLUSIONS: Due to the
      many built in quality control features MOIRAI is especially suitable to support
      the development of new sequencing based protocols. AVAILIABILITY: The MOIRAI
      source code is freely available at http://sourceforge.net/projects/moirai/.

PMID- 24884665
TI  - Synthesizing genetic sequential logic circuit with clock pulse generator.
AB  - BACKGROUND: Rhythmic clock widely occurs in biological systems which controls
      several aspects of cell physiology. For the different cell types, it is supplied
      with various rhythmic frequencies. How to synthesize a specific clock signal is a
      preliminary but a necessary step to further development of a biological computer
      in the future. RESULTS: This paper presents a genetic sequential logic circuit
      with a clock pulse generator based on a synthesized genetic oscillator, which
      generates a consecutive clock signal whose frequency is an inverse integer
      multiple to that of the genetic oscillator. An analogous electronic waveform
      shaping circuit is constructed by a series of genetic buffers to shape logic
      high/low levels of an oscillation input in a basic sinusoidal cycle and generate
      a pulse-width-modulated (PWM) output with various duty cycles. By controlling the
      threshold level of the genetic buffer, a genetic clock pulse signal with its
      frequency consistent to the genetic oscillator is synthesized. A synchronous
      genetic counter circuit based on the topology of the digital sequential logic
      circuit is triggered by the clock pulse to synthesize the clock signal with an
      inverse multiple frequency to the genetic oscillator. The function acts like a
      frequency divider in electronic circuits which plays a key role in the sequential
      logic circuit with specific operational frequency. CONCLUSIONS: A cascaded
      genetic logic circuit generating clock pulse signals is proposed. Based on
      analogous implement of digital sequential logic circuits, genetic sequential
      logic circuits can be constructed by the proposed approach to generate various
      clock signals from an oscillation signal.

PMID- 24884664
TI  - Improvement of spinal non-viral IL-10 gene delivery by D-mannose as a transgene
      adjuvant to control chronic neuropathic pain.
AB  - BACKGROUND: Peri-spinal subarachnoid (intrathecal; i.t.) injection of non-viral
      naked plasmid DNA encoding the anti-inflammatory cytokine, IL-10 (pDNA-IL-10)
      suppresses chronic neuropathic pain in animal models. However, two sequential
      i.t. pDNA injections are required within a discrete 5 to 72-hour period for
      prolonged efficacy. Previous reports identified phagocytic immune cells present
      in the peri-spinal milieu surrounding the i.t injection site that may play a role
      in transgene uptake resulting in subsequent IL-10 transgene expression. METHODS:
      In the present study, we aimed to examine whether factors known to induce pro
      phagocytic anti-inflammatory properties of immune cells improve i.t. IL-10
      transgene uptake using reduced naked pDNA-IL-10 doses previously determined
      ineffective. Both the synthetic glucocorticoid, dexamethasone, and the hexose
      sugar, D-mannose, were factors examined that could optimize i.t. pDNA-IL-10
      uptake leading to enduring suppression of neuropathic pain as assessed by light
      touch sensitivity of the rat hindpaw (allodynia). RESULTS: Compared to
      dexamethasone, i.t. mannose pretreatment significantly and dose-dependently
      prolonged pDNA-IL-10 pain suppressive effects, reduced spinal IL-1beta and
      enhanced spinal and dorsal root ganglia IL-10 immunoreactivity. Macrophages
      exposed to D-mannose revealed reduced proinflammatory TNF-alpha, IL-1beta, and
      nitric oxide, and increased IL-10 protein release, while IL-4 revealed no
      improvement in transgene uptake. Separately, D-mannose dramatically increased
      pDNA-derived IL-10 protein release in culture supernatants. Lastly, a single i.t.
      co-injection of mannose with a 25-fold lower pDNA-IL-10 dose produced prolonged
      pain suppression in neuropathic rats. CONCLUSIONS: Peri-spinal treatment with D
      mannose may optimize naked pDNA-IL-10 transgene uptake for suppression of
      allodynia, and is a novel approach to tune spinal immune cells toward pro
      phagocytic phenotype for improved non-viral gene therapy.

PMID- 24884666
TI  - Activation of coagulation and tissue fibrin deposition in experimental influenza
      in ferrets.
AB  - BACKGROUND: Epidemiological studies relate influenza infection with vascular
      diseases like myocardial infarction. The hypothesis that influenza infection has
      procoagulant effects on humans has been investigated by experimental animal
      models. However, these studies often made use of animal models only susceptible
      to adapted influenza viruses (mouse adapted influenza strains) or remained
      inconclusive. Therefore, we decided to study the influence of infection with
      human influenza virus isolates on coagulation in the well-established ferret
      influenza model. RESULTS: After infection with either a seasonal-, pandemic- or
      highly pathogenic avian influenza (HPAI-H5N1) virus strain infected animals
      showed alterations in hemostasis compared to the control animals. Specifically on
      day 4 post infection, a four second rise in both PT and aPTT was observed. D
      dimer concentrations increased in all 3 influenza groups with the highest
      concentrations in the pandemic influenza group. Von Willebrand factor activity
      levels increased early in infection suggesting endothelial cell activation. Mean
      thrombin-antithrombin complex levels increased in both pandemic and HPAI-H5N1
      virus infected ferrets. At tissue level, fibrin staining showed intracapillary
      fibrin deposition especially in HPAI-H5N1 virus infected ferrets. CONCLUSION:
      This study showed hemostatic alterations both at the circulatory and at the
      tissue level upon infection with different influenza viruses in an animal model
      closely mimicking human influenza virus infection. Alterations largely correlated
      with the severity of the respective influenza virus infections.

PMID- 24884667
TI  - Bipolar radiofrequency ablation is useful for treating atrial fibrillation
      combined with heart valve diseases.
AB  - BACKGROUND: Atrial fibrillation (AF) is a common arrhymia, and it results in
      increased risk of thromboembolism and decreased cardiac function. In patients
      undergoing cardiac surgery, concomitant radiofrequency ablation to treat AF is
      effective in restoring sinus rhythm (SR). This study is an observational cohort
      study aimed to investigate the safety and efficacy of bipolar radiofrequency
      ablation (BRFA) for treating AF combined with heart valve diseases. METHODS:
      Clinical data were analyzed retrospectively from 324 cases of rheumatic heart
      disease combined with persistent AF patients who underwent valve replacement
      concomitant BRFA. The modified left atrial and the simplified right atrial
      ablation were used for AF treatments. Of the 324 patients, 248 patients underwent
      mitral valve replacement and 76 patients underwent double valve replacement.
      Meanwhile, 54 patients underwent concomitant thrombectomy and 97 underwent
      tricuspid valvuloplasty. And all of them received temporary pacemaker
      implantation. The 24 hours holter electrocardiogram (ECG) monitoring and
      echocardiography was performed before the operation, on the first day after
      operation, on discharge day, and at 6 and 12 months after operation. RESULTS:
      There were 299 patients with SR on the first day after operation (92.30%), 12
      patients with junctional rhythm (3.70%), 11 patients with AF (3.39%), and 2
      patients with atrial flutter (0.62%). The temporary pacemaker was used in 213
      patients (65.74%) with heart rates less than 70 beat/minute in the ICU. Two
      patients died early and the mortality rate was 0.62%. Two patients had left
      ventricular rupture and the occurrence rate was 0.62%. They both recovered. There
      was no degree III atrioventricular blockage and no permanent pacemaker
      implantation. Overall survival rate was 99.38% (322 cases) with SR conversion
      rate of 89.13% (287 cases) at discharge. The SR conversion rate was 87.54% and
      87.01% at 6 and 12 months after operation. Sinus bradycardia occurred in 3.42% of
      patients at 6 months after operation and in 3.03% of patients at 12 months after
      operation. Echocardiography showed that the left atrial diameter was
      significantly decreased, and ejection fraction and fractional shortening were
      significantly improved. CONCLUSIONS: BRFA for treating AF in concomitant valve
      replacement is safe and with good efficacy.

PMID- 24884668
TI  - Oral health survey and oral health questionnaire for high school students in
      Tibet, China.
AB  - OBJECTIVES: The aim of this study is to identify the oral health status as well
      as oral health practices and access for care of graduating senior high school
      Tibetan students in Shannan prefecture of Tibet. METHODS: Based on standards of
      the 3rd Chinese National Oral Epidemiological Survey and WHO Oral Health Surveys,
      1907 graduating students from three senior high schools were examined for caries,
      periodontitis, dental fluorosis, and oral hygiene status. The questionnaire to
      the students addressed oral health practices and present access to oral medical
      services. RESULTS: Dental caries prevalence (39.96%) and mean DMFT (0.97) were
      high in Tibetan students. In community periodontal indexes, the detection rate of
      gingivitis and dental calculus were 59.50% and 62.64%, respectively. Oral hygiene
      index-simplified was 0.69, with 0.36 and 0.33 in debris index-simplified and
      calculus index-simplified, respectively. Community dental fluorosis index was
      0.29, with 8.13% in prevalence rate. The questionnaire showed students had poor
      oral health practices and unawareness for their needs for oral health services.
      It was also noted that the local area provides inadequate oral medical services.
      CONCLUSIONS: Tibetan students had higher prevalence of dental diseases and lower
      awareness of oral health needs. The main reasons were geographical environment,
      dietary habit, students' attitude to oral health, and lack of oral health
      promotion and education. Oral health education and local dentists training should
      be strengthened to get effective prevention of dental diseases.

PMID- 24884669
TI  - Mitochondria as signaling organelles.
AB  - Almost 20 years ago, the discovery that mitochondrial release of cytochrome c
      initiates a cascade that leads to cell death brought about a wholesale change in
      how cell biologists think of mitochondria. Formerly viewed as sites of
      biosynthesis and bioenergy production, these double membrane organelles could now
      be thought of as regulators of signal transduction. Within a few years, multiple
      other mitochondria-centric signaling mechanisms have been proposed, including
      release of reactive oxygen species and the scaffolding of signaling complexes on
      the outer mitochondrial membrane. It has also been shown that mitochondrial
      dysfunction causes induction of stress responses, bolstering the idea that
      mitochondria communicate their fitness to the rest of the cell. In the past
      decade, multiple new modes of mitochondrial signaling have been discovered. These
      include the release of metabolites, mitochondrial motility and dynamics, and
      interaction with other organelles such as endoplasmic reticulum in regulating
      signaling. Collectively these studies have established that mitochondria
      dependent signaling has diverse physiological and pathophysiological outcomes.
      This review is a brief account of recent work in mitochondria-dependent signaling
      in the historical framework of the early studies. 

PMID- 24884670
TI  - General practice and ethnicity: an experimental study of doctoring.
AB  - BACKGROUND: There is extensive evidence of health inequality across ethnic
      groups. Inequity is a complex social phenomenon involving several underlying
      factors, including ethnic discrimination. In the field of health care, it has
      been established that ethnic discrimination stems partially from bias or
      prejudice on the part of doctors. Indeed, it has been hypothesized that patient
      ethnicity may affect doctors' social cognition, thus modifying their social
      interactions and decision-making processes. General practitioners (GPs) are the
      primary access point to health care for ethnic minority groups. In this study, we
      examine whether patient ethnicity affects the relational and decisional features
      of doctoring. METHODS: The sample was made up of 171 Belgian GPs, who were each
      randomly allocated to one of two experimental conditions. One group were given a
      hypertension vignette case with a Belgian patient (non-minority patient), while
      the other group were given a hypertension vignette case with a Moroccan patient
      (minority patient). We evaluated the time devoted by GPs to examining medical
      history; time devoted by GPs to examining socio-relational history;
      cardiovascular risk assessments by GPs; electrocardiogram (ECG) recommendations
      by GPs, and drug prescriptions by GPs. RESULTS: We observed that for ethnic
      minority patients, GPs prescribed more drugs and devoted less time to examining
      socio-relational history. Neither cardiovascular risk assessments nor ECG
      recommendations were affected by patient ethnicity. GPs who were very busy
      devoted less time to examining medical history when dealing with minority
      patients. CONCLUSIONS: We found no evidence that GPs discriminated against ethnic
      minority patients when it came to medical decisions. However, our study did
      identify a risk of drugs being used inappropriately in some ethnic-specific
      encounters. We also observed that, with ethnic minority patients, GPs engage less
      in the relational dimension of doctoring, particularly when working within a
      demanding environment. In general practice, the quality of the relationship
      between doctor and patient is an essential component of the effective management
      of chronic illness. Our research highlights the complexity of ethnic
      discrimination in general practice, and the need for further studies.

PMID- 24884671
TI  - Two M-T hook residues greatly improve the antiviral activity and resistance
      profile of the HIV-1 fusion inhibitor SC29EK.
AB  - BACKGROUND: Peptides derived from the C-terminal heptad repeat (CHR) of HIV-1
      gp41 such as T20 (Enfuvirtide) and C34 are potent viral fusion inhibitors. We
      have recently found that two N-terminal residues (Met115 and Thr116) of CHR
      peptides form a unique M-T hook structure that can greatly enhance the binding
      and anti-HIV activity of inhibitors. Here, we applied two M-T hook residues to
      optimize SC29EK, an electrostatically constrained peptide inhibitor with a potent
      anti-HIV activity. RESULTS: The resulting peptide MT-SC29EK showed a dramatically
      increased binding affinity and could block the six-helical bundle (6-HB)
      formation more efficiently. As expected, MT-SC29EK potently inhibited HIV-1 entry
      and infection, especially against those T20- and SC29EK-resistant HIV-1 variants.
      More importantly, MT-SC29EK and its short form (MT-SC22EK) suffered from the
      difficulty to induce HIV-1 resistance during the in vitro selection, suggesting
      their high genetic barriers to the development of resistance. CONCLUSIONS: Our
      studies have verified the M-T hook structure as a vital strategy to design novel
      HIV-1 fusion inhibitors and offered an ideal candidate for clinical development.

PMID- 24884672
TI  - Is performance in goal oriented head movements altered in patients with tension
      type headache?
AB  - BACKGROUND: Head repositioning tasks have been used in different experimental and
      clinical contexts to quantitatively measure motor control performance. Effects of
      pain on sensorimotor control have often been described in various musculoskeletal
      conditions and may provide relevant information with regard to potential
      mechanisms underlying tension-type headaches. The purpose of the current study
      was to compare the performance of patients with tension-type headache and healthy
      participants in a cervical aiming task using the Fitts' task paradigm. METHODS:
      Patients with tension-type headache and healthy controls were compared in a
      cervical aiming task. Participants were asked to move their head as quickly, and
      precisely as possible to a target under various experimental conditions.
      Dependent variables included movement time, variable error, constant error and
      absolute error. RESULTS: As predicted by Fitts' law, decreasing target size and
      increasing head rotation amplitudes yielded longer movement times in both groups.
      Participants with tension-type headache, when compared to healthy participants
      showed a significant increase in both constant and absolute errors for each of
      the four conditions. CONCLUSION: Decreased motor performance was observed in
      participants with tension-type headache, likely due to altered motor control of
      the neck musculature. Future research is warranted to investigate the clinical
      aspect related to decrease in motor performance.

PMID- 24884673
TI  - Lower than expected hepatitis B virus infection prevalence among first generation
      Koreans in the U.S.: results of HBV screening in the Southern California Inland
      Empire.
AB  - BACKGROUND: Hepatitis B virus (HBV) infection is prevalent in Asian immigrants in
      the USA. California's Inland Empire region has a population of approximately four
      million, including an estimated 19,000 first generation Koreans. Our aim was to
      screen these adult individuals to establish HBV serological diagnoses, educate,
      and establish linkage to care. METHODS: A community-based program was conducted
      in Korean churches from 11/2009 to 2/2010. Subjects were asked to complete a HBV
      background related questionnaire, provided with HBV education, and tested for
      serum HBsAg, HBsAb and HBcAb. HBsAg positive subjects were tested for HBV
      quantitative DNA, HBeAg and HBeAb, counseled and directed to healthcare
      providers. Subjects unexposed to HBV were invited to attend a HBV vaccination
      clinic. RESULTS: A total of 973 first generation Koreans were screened, aged
      52.3y (18-93y), M/F: 384/589. Most (75%) had a higher than high school education
      and were from Seoul (62.2%). By questionnaire, 24.7% stated they had been
      vaccinated against HBV. The serological diagnoses were: HBV infected (3.0%),
      immune due to natural infection (35.7%), susceptible (20.1%), immune due to
      vaccination (40.3%), and other (0.9%). Men had a higher infection prevalence
      (4.9% vs. 1.7%, p = 0.004) and a lower vaccination rate (34.6% vs. 44.0%, p =
      0.004) compared to women. Self-reports of immunization status were incorrect for
      35.1% of subjects. CONCLUSIONS: This large screening study in first generation
      Koreans in Southern California demonstrates: 1) a lower than expected HBV
      prevalence (3%), 2) a continued need for vaccination, and 3) a need for screening
      despite a reported history of vaccination.

PMID- 24884674
TI  - Salmonella enterica serovar Virchow meningitis in a young man in Italy: a case
      report.
AB  - INTRODUCTION: Salmonella enterica is a leading cause of foodborne infections
      worldwide and includes more than 2500 different serovars, causing primarily
      gastroenteritis. However, the infection may occur elsewhere and produce
      characteristic clinical syndromes. Meningitis is a rare complication that occurs
      in less than 1% of clinical salmonellosis. CASE PRESENTATION: We describe a case
      of Salmonella Virchow meningitis in a 36-year-old Caucasian man presenting with
      headache in the occipital region, associated fever, nausea and vomiting, dyspnea
      and ambulatory difficulty. The cerebrospinal fluid culture showed growth of
      Salmonella, later confirmed to be Salmonella enterica serovar Virchow.
      CONCLUSIONS: Salmonella Virchow infection is rare and this report highlights the
      risk of meningitis as a presentation of salmonellosis. To the best of our
      knowledge this is the first Italian case of meningitis due to Salmonella Virchow
      in a young adult. The probable route of transmission remains unclear and a long
      carriage state after a previous episode of gastroenteritis should be considered.

PMID- 24884675
TI  - Discovery, optimization, and biological evaluation of 5-(2
      (trifluoromethyl)phenyl)indazoles as a novel class of transient receptor
      potential A1 (TRPA1) antagonists.
AB  - A high throughput screening campaign identified 5-(2-chlorophenyl)indazole
      compound 4 as an antagonist of the transient receptor potential A1 (TRPA1) ion
      channel with IC50 = 1.23 MUM. Hit to lead medicinal chemistry optimization
      established the SAR around the indazole ring system, demonstrating that a
      trifluoromethyl group at the 2-position of the phenyl ring in combination with
      various substituents at the 6-position of the indazole ring greatly contributed
      to improvements in vitro activity. Further lead optimization resulted in the
      identification of compound 31, a potent and selective antagonist of TRPA1 in
      vitro (IC50 = 0.015 MUM), which has moderate oral bioavailability in rodents and
      demonstrates robust activity in vivo in several rodent models of inflammatory
      pain.

PMID- 24884676
TI  - Genome-wide identification of heat shock proteins (Hsps) and Hsp interactors in
      rice: Hsp70s as a case study.
AB  - BACKGROUND: Heat shock proteins (Hsps) perform a fundamental role in protecting
      plants against abiotic stresses. Although researchers have made great efforts on
      the functional analysis of individual family members, Hsps have not been fully
      characterized in rice (Oryza sativa L.) and little is known about their
      interactors. RESULTS: In this study, we combined orthology-based approach with
      expression association data to screen rice Hsps for the expression patterns of
      which strongly correlated with that of heat responsive probe-sets. Twenty-seven
      Hsp candidates were identified, including 12 small Hsps, six Hsp70s, three
      Hsp60s, three Hsp90s, and three clpB/Hsp100s. Then, using a combination of
      interolog and expression profile-based methods, we inferred 430 interactors of
      Hsp70s in rice, and validated the interactions by co-localization and function
      based methods. Subsequent analysis showed 13 interacting domains and 28 target
      motifs were over-represented in Hsp70s interactors. Twenty-four GO terms of
      biological processes and five GO terms of molecular functions were enriched in
      the positive interactors, whose expression levels were positively associated with
      Hsp70s. Hsp70s interaction network implied that Hsp70s were involved in
      macromolecular translocation, carbohydrate metabolism, innate immunity,
      photosystem II repair and regulation of kinase activities. CONCLUSIONS: Twenty
      seven Hsps in rice were identified and 430 interactors of Hsp70s were inferred
      and validated, then the interacting network of Hsp70s was induced and the
      function of Hsp70s was analyzed. Furthermore, two databases named Rice Heat Shock
      Proteins (RiceHsps) and Rice Gene Expression Profile (RGEP), and one online tool
      named Protein-Protein Interaction Predictor (PPIP), were constructed and could be
      accessed at http://bioinformatics.fafu.edu.cn/.

PMID- 24884677
TI  - Protective effects of pomegranate (Punica granatum) juice on testes against
      carbon tetrachloride intoxication in rats.
AB  - BACKGROUND: Pomegranate fruit has been extensively used as a natural medicine in
      many cultures. The present study was aimed at evaluating the protective effects
      of pomegranate (Punica granatum) juice against carbon tetrachloride (CCl4)
      induced oxidative stress and testes injury in adult Wistar rats. METHODS: Twenty
      eight Wistar albino male rats were divided equally into 4 groups for the
      assessment of protective potential of pomegranate juice. Rats of group I
      (control) received only vehicles and had free access to food and water. Rats of
      groups II and IV were treated with CCl4 (2 ml/kg bwt) via the intraperitoneal
      route once a week for ten weeks. The pomegranate juice was supplemented via
      drinking water 2 weeks before and concurrent with CCl4 treatment to group IV.
      Group III was supplemented with pomegranate juice for twelve weeks. The
      protective effects of pomegranate on serum sex hormones, oxidative markers,
      activities of antioxidant enzymes and histopathology of testes were determined in
      CCl4-induced reproductive toxicity in rats. RESULTS: Pomegranate juice showed
      significant elevation in testosterone, luteinizing hormone (LH) and follicle
      stimulating hormone (FSH) those depleted by the injection of CCl4. Activity
      levels of endogenous testesticular antioxidant enzymes; superoxide dismutase
      (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase
      (GST) and glutathione reductase (GR) and glutathione (GSH) contents were
      increased while lipid peroxidation (LPO) and nitric oxide (NO) were decreased
      with pomegranate juice. Moreover, degeneration of germ and Leydig cells along
      with deformities in spermatogenesis induced after CCl4 injections were restored
      with the treatment of pomegranate juice. CONCLUSION: The results clearly
      demonstrated that pomegranate juice augments the antioxidant defense mechanism
      against carbon tetrachloride-induced reproductive toxicity and provides evidence
      that it may have a therapeutic role in free radical mediated diseases.

PMID- 24884678
TI  - Extending the authority for sickness certification beyond the medical profession:
      the importance of 'boundary work'.
AB  - BACKGROUND: The study aimed to explore the views of general practitioners (GPs),
      nurses and physiotherapists towards extending the role of sickness certification
      beyond the medical profession in primary care. METHODS: Fifteen GPs, seven nurses
      and six physiotherapists were selected to achieve varied respondent
      characteristics including sex, geographical location, service duration and post
      graduate specialist training. Constant-comparative qualitative analysis of data
      from 28 semi-structured telephone interviews was undertaken. RESULTS: The
      majority of respondents supported the extended role concept; however members of
      each professional group also rejected the notion. Respondents employed four
      different legitimacy claims to justify their views and define their occupational
      boundaries in relation to sickness certification practice. Condition-specific
      legitimacy, the ability to adopt a holistic approach to sickness certification,
      system efficiency and control-related arguments were used to different degrees by
      each occupation. Practical suggestions for the extension of the sickness
      certification role beyond the medical profession are underpinned by the
      sociological theory of professional identity. CONCLUSIONS: Extending the
      authority to certify sickness absence beyond the medical profession is not simply
      a matter of addressing practical and organisational obstacles. There is also a
      need to consider the impact on, and preferences of, the specific occupations and
      their respective boundary claims. This paper explores the implications of
      extending the sick certification role beyond general practice. We conclude that
      the main policy challenge of such a move is to a) persuade GPs to relinquish this
      role (or to share it with other professions), and b) to understand the 'boundary
      work' involved.

PMID- 24884679
TI  - Service usage and vascular complications in young adults with type 1 diabetes.
AB  - BACKGROUND: Few studies have examined young adults with type 1 diabetes use of
      health services and the development of vascular complications. As part of the
      Youth Outreach for Diabetes (YOuR-Diabetes) project, this study identified health
      service usage, the prevalence and factors predictive of development of vascular
      complications (hypertension, retinopathy and nephropathy) in a cohort of young
      adults (aged 16-30 years) with type 1 diabetes in Hunter New England and the
      Lower Mid-North Coast area of New South Wales, Australia. METHODS: A cross
      sectional retrospective documentation survey was undertaken of case notes of
      young adults with type 1 diabetes accessing Hunter New England Local Health
      District public health services in 2010 and 2011, identified through ambulatory
      care clinic records, hospital attendances and other clinical records. Details of
      service usage, complications screening and evidence of vascular complications
      were extracted. Independent predictors were modelled using linear and logistic
      regression analyses. RESULTS: A cohort of 707 patients were reviewed; mean (SD)
      age was 23.0 (3.7) years, with mean diabetes duration of 10.2 (5.8, range 0.2 -
      28.3) years; 42.4% lived/ 23.1% accessed services in non-metropolitan
      areas.Routine preventative service usage was low and unplanned contacts high;
      both deteriorated with increasing age. Low levels of complications screening were
      found. Where documented, hypertension, particularly, was common, affecting 48.4%
      across the study period. Diabetes duration was a strong predictor of vascular
      complications along with glycaemic control; hypertension was linked with renal
      dysfunction. CONCLUSION: Findings indicate a need to better understand young
      people's drivers and achievements when accessing services, and how services can
      be reconfigured or delivered differently to better meet their needs and achieve
      better outcomes. Regular screening is required using current best practice
      guidelines as this affords the greatest chance for early complication detection,
      treatment initiation and secondary prevention.

PMID- 24884680
TI  - Ivy gourd (Coccinia grandis L. Voigt) root suppresses adipocyte differentiation
      in 3T3-L1 cells.
AB  - BACKGROUND: Ivy gourd (Coccinia grandis L. Voigt) is a tropical plant widely
      distributed throughout Asia, Africa, and the Pacific Islands. The anti-obesity
      property of this plant has been claimed but still remains to be scientifically
      proven. We therefore investigated the effects of ivy gourd leaf, stem, and root
      on adipocyte differentiation by employing cell culture model. METHODS: Dried
      roots, stems, and leaves of ivy gourd were separately extracted with ethanol.
      Each extract was then applied to 3T3-L1 pre-adipocytes upon induction with a
      mixture of insulin, 3-isobutyl-1-methylxanthine, and dexamethasone, for anti
      adipogenesis assay. The active extract was further fractionated by a sequential
      solvent partitioning method, and the resulting fractions were examined for their
      abilities to inhibit adipogenesis in 3T3-L1 cells. Differences in the expression
      of adipogenesis-related genes between the treated and untreated cells were
      determined from their mRNA and protein levels. RESULTS: Of the three ivy gourd
      extracts, the root extract exhibited an anti-adipogenic effect. It significantly
      reduced intracellular fat accumulation during the early stages of adipocyte
      differentiation. Together with the suppression of differentiation, expression of
      the genes encoding PPARgamma, C/EBPalpha, adiponectin, and GLUT4 were down
      regulated. Hexane-soluble fraction of the root extract also inhibited adipocyte
      differentiation and decreased the mRNA levels of various adipogenic genes in the
      differentiating cells. CONCLUSIONS: This is the first study to demonstrate that
      ivy gourd root may prevent obesity based mainly on the ability of its active
      constituent(s) to suppress adipocyte differentiation in vitro. Such an inhibitory
      effect is mediated by at least down-regulating the expression of PPARgamma-the
      key transcription factor of adipogenesis in pre-adipocytes during their early
      differentiation processes.

PMID- 24884682
TI  - The relations of family members' unique and shared perspectives of family
      dysfunction to dyad adjustment.
AB  - Among a community sample of families (N = 128), this study examined how family
      members' shared and unique perspectives of family dysfunction relate to dyad
      members' shared views of dyad adjustment within adolescent-mother, adolescent
      father, and mother-father dyads. Independent of a family's family perspective
      (shared perspective of family dysfunction), the adolescent's unique perspective
      was associated with lower security and higher conflict with both mother and
      father; the father's unique perspective was associated with lower security and
      higher conflict with the adolescent, as well as lower marital quality with
      mother; and the mother unique perspective was associated with lower marital
      quality with the father. Moreover, for adolescent-parent dyads, compared with the
      parent unique perspective, the adolescent unique perspective was more strongly
      associated with dyad adjustment. These findings indicate that both shared and
      unique views of the family system-the adolescent's unique view in particular
      independently relate to the health of family subsystems. They also suggest that
      research, as well as therapeutic interventions, that focus on just the shared
      view of the family may miss important elements of family dysfunction.

PMID- 24884681
TI  - West Nile virus neuroinvasive disease: neurological manifestations and
      prospective longitudinal outcomes.
AB  - BACKGROUND: West Nile Virus (WNV) is a mosquito-borne flavivirus that has caused
      ongoing seasonal epidemics in the United States since 1999. It is estimated that
      <=1% of WNV-infected patients will develop neuroinvasive disease (West Nile
      encephalitis and/or myelitis) that can result in debilitating morbidities and
      long-term sequelae. It is essential to collect longitudinal information about the
      recovery process and to characterize predicative factors that may assist in
      therapeutic decision-making in the future. METHODS: We report a longitudinal
      study of the neurological outcomes (as measured by neurological examination,
      Glascow Coma Scale, and Modified Mini-Mental State Examination) for 55 subjects
      with WNV neuroinvasive disease (confirmed by positive CSF IgM) assessed on day 7,
      at discharge, and on days 14, 30, and 90. The neurological outcome measures were
      coma (presence and degree), global cognitive status, presence of cranial
      neuropathy, tremors and/or weakness. RESULTS: At initial clinical presentation
      93% presented with a significant neurological deficit (49% with weakness, 35%
      with tremor, and 16% with cranial neuropathy). The number of patients with a
      cognitive deficit fell from 25 at initial evaluation to 9 at their last
      evaluation. Cranial neuropathy was present in 9 at onset and in only 4 patients
      at study conclusion. Of the 19 patients who had a tremor at enrollment, 11
      continued to exhibit a tremor at follow-up. Seven patients died after initial
      enrollment in the study, with 5 of those having presented in a coma. The factors
      that predict either severity or long-term recovery of neurological function
      include age (older individuals were weaker at follow-up examination), gender
      (males recovered better from coma), and presentation in a coma with cranial nerve
      deficits (had a poorer recovery particularly with regard to cognition).
      CONCLUSIONS: This study represents one of the largest clinical investigations
      providing prospectively-acquired neurological outcomes data among American
      patients with WNV central nervous system disease. The findings show that the
      factors that influence prognosis from the initial presentation include age,
      gender, and specific neurological deficits at onset. TRIAL REGISTRATION:
      ClinicalTrials.gov identifier: NCT00138463 and NCT00069316.

PMID- 24884683
TI  - Synthesis and activity of three new trinuclear platinums with cis-geometry for
      terminal metal centres.
AB  - BACKGROUND: As compared to cisplatin, trinuclear platinum compounds such as
      BBR3464 and DH6Cl have an altered spectrum of activity possibly because they form
      long-range adducts with DNA as against mainly intrastrand 1,2-bifunctional
      adducts formed by cisplatin and its analogues. Because of the labilizing effect
      associated with the trans-geometry, the compounds are expected to break down
      inside the cell thus serving to reduce the number of long-range adducts formed.
      In contrast, trinuclear platinum complexes with cis-geometry for the terminal
      metal centres would be less subject to such breakdown and hence may produce a
      greater number of long-range inter- and intrastrand adducts with the DNA. This
      paper describes the synthesis and activity against human ovarian tumour models of
      of three new trinuclear platinum complexes with cis-geometry for terminal
      platinum centres, coded as QH4, QH7 and QH8. The paper also describes cellular
      accumulation of platinum, level of drug-DNA binding, and nature of interaction of
      the compounds with pBR322 plasmid DNA. RESULTS: Methods of synthesis, elemental
      analysis, spectral studies and molar conductivity measurements provide support to
      the suggested structures of the compounds. QH4 and QH8 are found to be more
      cytotoxic than cisplatin against the parental A2780 cell line; QH8 is more active
      than cisplatin against the resistant A2780cisR and A2780ZD0473R cell lines as
      well. The least compound QH7 shows a greater activity against the resistant cell
      lines than the parental cell line; it is most damaging to pBR322 plasmid DNA and
      most able to induce changes in DNA conformation. The variations in activity of
      the compounds, changes in intracellular drug accumulation and levels of Pt-DNA
      binding with the changes in number of planaramine ligands bound to central
      platinum and the length of the linking diamines, can be seen (1) to illustrate
      structure-activity relationships and (2) to highlight that the relationship
      between antitumour activity and interaction with cellular platinophiles including
      DNA can be quite complex as the cell death is carried out by downstream processes
      in the cell cycle where many proteins are involved. CONCLUSION: Among the three
      designed trinuclear platinum complexes with cis-geometry for the terminal metal
      centres, the most active compound QH8 is found to be more active than cisplatin
      against the parental A2780 and the resistant A2780cisR and A2780ZD0473R cell
      lines.

PMID- 24884684
TI  - Sealing versus partial caries removal in primary molars: a randomized clinical
      trial.
AB  - BACKGROUND: The resin-based pit and fissure sealant is considered a successful
      tool in caries prevention, however there is a growing evidence of its use in
      controlling already established caries in posterior teeth. The aim of this
      clinical trial is to verify the efficacy of pit and fissure sealants in arresting
      dentinal caries lesions compared to partial excavation and restorative treatment
      in primary molar teeth. METHODS: Thirty six patients with occlusal cavitated
      primary molar reaching outer half of dentin were selected. The patients were
      randomly allocated into two groups: sealant application (experimental group - n =
      17) and restoration with composite resin (control group - n = 19). Clinical and
      radiograph evaluation were performed after 6, 12 and 18 months. The chi-square
      test was used to verify the distribution of characteristics variables of the
      sample among the groups. The survival rate of treatments was evaluated using
      Kaplan-Meier survival and log-rank test. Fisher's Exact and logistic regression
      tests were calculated in each evaluation period (alpha = 5%). RESULTS: The
      control group showed significantly better clinical survival after 18 months (p =
      0.0025). In both groups, no caries progression was registered on the radiographic
      evaluations. CONCLUSIONS: Sealing had similar efficacy in the arrestment of
      caries progression of cavitated occlusal lesions compared to partial excavation
      of the lesions, even though the frequency of re-treatments was significantly
      higher in sealed lesions. TRIAL REGISTRATION: Registro Brasileiro de Ensaios
      Clinicos (ReBEC): RBR-9kkv53.

PMID- 24884685
TI  - Chelation of Ca2+ ions by a peptide from the repeat region of the Plasmodium
      falciparum circumsporozoite protein.
AB  - BACKGROUND: Elegant efforts towards the determination of the structural
      tendencies of peptides derived from the Plasmodium falciparum circumsporozoite
      protein allowed the proposal of a left-handed helical conformation for this
      protein. The use of circular dichroism and Fourier-transformed infrared
      spectroscopy applied to various peptides derived from this protein, indicated
      that they bind Ca2+ ions in helical environments. The essential role of calcium
      in cell function and biological mechanisms is well known. It influences the
      development of several stages of the P. falciparum parasite. However, there is
      very little knowledge regarding calcium coordination to circumsporozoite
      proteins. In the present investigation the chelation of Ca2+ by the
      (NANPNVDP)3NANP peptide, which contains the first seven 4-amino-acid blocks of
      the repeat region of the P. falciparum circumsporozoite protein, is tested with
      the use of circular dichroism and nuclear magnetic resonance spectroscopies.
      Spectroscopy-based solution conformations of the Ca-bound peptide are also
      determined. METHODS: NMR spectroscopy and circular dichroism were used to test
      Ca2+ coordination by the peptide (NANPNVDP)3NANP. Solution conformations for the
      Ca-bound peptide were determined through molecular dynamics calculations.
      RESULTS: The NMR spectra collected for (NANPNVDP)3NANP indicate that the signals
      generated by some of the amino acids located at its C-terminal end are shifted
      from their original positions upon Ca2+ addition. The solution conformations
      determined for the Ca-bound peptide indicate that the metal ion can be either six
      or seven-coordinate. CONCLUSIONS: The investigation described herein strongly
      supports the coordination of Ca2+ ions to some of the amino acids located at the
      C-terminus of the peptide (NANPNVDP)3NANP. The solution conformations determined
      for the Ca-bound congener of this peptide display many structural features
      associated to Ca-binding proteins.

PMID- 24884687
TI  - Molecular and pathological insights into Chlamydia pecorum-associated sporadic
      bovine encephalomyelitis (SBE) in Western Australia.
AB  - BACKGROUND: Despite its global recognition as a ruminant pathogen, cases of
      Chlamydia pecorum infection in Australian livestock are poorly documented. In
      this report, a C. pecorum specific Multi Locus Sequence Analysis scheme was used
      to characterise the C. pecorum strains implicated in two cases of sporadic bovine
      encephalomyelitis confirmed by necropsy, histopathology and immunohistochemistry.
      This report provides the first molecular evidence for the presence of mixed
      infections of C. pecorum strains in Australian cattle. CASE PRESENTATION:
      Affected animals were two markedly depressed, dehydrated and blind calves, 12 and
      16 weeks old. The calves were euthanized and necropsied. In one calf, a severe
      fibrinous polyserositis was noted with excess joint fluid in all joints whereas
      in the other, no significant lesions were seen. No gross abnormalities were noted
      in the brain of either calf. Histopathological lesions seen in both calves
      included: multifocal, severe, subacute meningoencephalitis with vasculitis,
      fibrinocellular thrombosis and malacia; diffuse, mild, acute interstitial
      pneumonia; and diffuse, subacute epicarditis, severe in the calf with gross
      serositis. Immunohistochemical labelling of chlamydial antigen in brain, spleen
      and lung from the two affected calves and brain from two archived cases,
      localised the antigen to the cytoplasm of endothelium, mesothelium and
      macrophages. C. pecorum specific qPCR, showed dissemination of the pathogen to
      multiple organs. Phylogenetic comparisons with other C. pecorum bovine strains
      from Australia, Europe and the USA revealed the presence of two genetically
      distinct sequence types (ST). The predominant ST detected in the brain, heart,
      lung and liver of both calves was identical to the C. pecorum ST previously
      described in cases of SBE. A second ST detected in an ileal tissue sample from
      one of the calves, clustered with previously typed faecal bovine isolates.
      CONCLUSION: This report provides the first data to suggest that identical C.
      pecorum STs may be associated with SBE in geographically separated countries and
      that these may be distinct from those found in the gastrointestinal tract. This
      report provides a platform for further investigations into SBE and for
      understanding the genetic relationships that exist between C. pecorum strains
      detected in association with other infectious diseases in livestock.

PMID- 24884688
TI  - An ancient satellite DNA has maintained repetitive units of the original
      structure in most species of the living fossil plant genus Zamia.
AB  - ZpS1 satellite DNA is specific to the genus Zamia and presents repetitive units
      organized as long arrays and also as very short arrays dispersed in the genome.
      We have characterized the structure of the ZpS1 repeats in 12 species
      representative of the whole geographic distribution of the genus. In most
      species, the clone most common sequences (cMCS) were so similar that a general
      most common sequence (GMCS) of the ZpS1 repetitive unit in the genus could be
      obtained. The few partial variations from the GMCS found in cMCS of some species
      correspond to variable positions present in most other species, as indicated by
      the clone consensus sequences (cCS). Two species have an additional species
      specific variety of ZpS1 satellite. The dispersed repeats were found to contain
      more mutations than repeats from long arrays. Our results indicate that all or
      most species of Zamia inherited the ZpS1 satellite from a common ancestor in
      Miocene and have maintained repetitive units of the original structure till
      present. The features of ZpS1 satellite in the genus Zamia are poorly compatible
      with the model of concerted evolution, but they are perfectly consistent with a
      new model of satellite evolution based on experimental evidences indicating that
      a specific amplification-substitution repair mechanism maintains the homogeneity
      and stability of the repeats structure in each satellite DNA originally present
      in a species as long as the species exists. 

PMID- 24884686
TI  - A newborn with grouped facial skin lesions and subsequent seizures.
AB  - BACKGROUND: Congenital grouped skin lesions are alarming signs of a variety of
      threatening diagnoses of quite different origin. The present case report shows an
      impressive clinical pattern of a neonate and illustrates the difficulty in
      differential diagnosis of mixed connective tissue disease and neonatal lupus
      erythematosus in newborns. This reported case is to our knowledge the first
      description of an unrecognized mixed connective tissue disease in the mother with
      an unusual clinical manifestation in the newborn, comprising skin lesions,
      neurological damage and non-typical antibody constellation. CASE PRESENTATION: We
      report on a Caucasian female neonate from a perinatally asymptomatic mother, who
      presented with grouped facial pustular-like skin lesions, followed by focal
      clonic seizures caused by multiple ischemic brain lesions. Herpes simplex virus
      infection was excluded and both the mother and her infant had the antibody
      pattern of systemic lupus erythematosus and neonatal lupus erythematosus,
      respectively. However, clinical signs in the mother showed overlapping features
      of mixed connective tissue disease. CONCLUSION: This case report emphasizes
      congenital Lupus erythematosus and mixed connective tissue disease as important
      differential diagnoses of grouped skin lesions in addition to Herpes simplex
      virus-infection. The coexistence of different criteria for mixed connective
      tissue disease makes it difficult to allocate precisely maternal and congenital
      infantile disease.

PMID- 24884689
TI  - Comparative analyses of a putative Francisella conjugative element.
AB  - A large circular plasmid detected in Francisella novicida-like strain PA10-7858,
      designated pFNPA10, was sequenced completely and analyzed. This 41,013-bp plasmid
      showed no homology to any of the previously sequenced Francisella plasmids and
      was 8-10 times larger in size than them. A total of 57 ORFs were identified
      within pFNPA10 and at least 9 of them encoded putative proteins with homology to
      different conjugal transfer proteins. The presence of iteron-like direct repeats
      and an ORF encoding a putative replication protein within pFNPA10 suggested that
      it replicated by the theta mode. Phylogenetic analyses indicated that pFNPA10 had
      no near neighbors in the databases and that it may have originated within an
      environmental Francisella lineage. Based on its features, pFNPA10 appears to be a
      novel extra-chromosomal genetic element within the genus Francisella. The
      suitability of pFNPA10 as a vector for transformation of species of Francisella
      by conjugation remains to be explored.

PMID- 24884690
TI  - Sequence analysis of single-copy genes in two wild olive subspecies: nucleotide
      diversity and potential use for testing admixture.
AB  - The wild olive distribution extends from the Mediterranean region to south Asia
      and Austral Africa. The species is also invasive, particularly in Australia.
      Here, we investigated the sequence variation at five nuclear single-copy genes in
      41 native and invasive accessions of the Mediterranean and African olive
      subspecies. The nucleotide diversity was assessed and the phylogenetic
      relationships between alleles were depicted with haplotype networks. A Bayesian
      clustering method (STRUCTURE) was applied to identify the main gene pools. We
      found an average of 18.4 alleles per locus. Native Mediterranean and African
      olives only share one allele, which testifies for ancient admixture on the Red
      Sea hills. The presence of divergent alleles in the Mediterranean olive, as well
      as the identification of two main genetic clusters, suggests a complex origin
      with two highly differentiated gene pools from the eastern and western
      Mediterranean that recently admixed. In the invasive range, relatively high
      nucleotide diversity is observed as a consequence of the introduction of alleles
      from two subspecies. Our data confirm that four invasive individuals are early
      generation hybrids. Finally, the utility of single-copy gene sequences in olive
      population genomic and phylogenetic studies is briefly discussed. 

PMID- 24884691
TI  - Genetic structure of the four wild tomato species in the Solanum peruvianum s.l.
      species complex.
AB  - The most diverse wild tomato species Solanum peruvianum sensu lato (s.l.) has
      been reclassified into four separate species: Solanum peruvianum sensu stricto
      (s.s.), Solanum corneliomuelleri, Solanum huaylasense, and Solanum arcanum.
      However, reproductive barriers among the species are incomplete and this can lead
      to discrepancies regarding genetic identity of germplasm. We used genotyping by
      sequencing (GBS) of S. peruvianum s.l., Solanum neorickii, and Solanum
      chmielewskii to develop tens of thousands of mapped single nucleotide
      polymorphisms (SNPs) to analyze genetic relationships within and among species.
      The data set was condensed to 14,043 SNPs with no missing data across 46 sampled
      plants. Origins of accessions were mapped using geographical information systems
      (GIS). Isolation by distance, pairwise genetic distances, and number of clusters
      were estimated using population genetics approaches. Isolation by distance was
      strongly supported, especially between interspecific pairs. Eriopersicon (S.
      peruvianum s.s., S. corneliomuelleri, S. huaylasense) and Arcanum (S. arcanum, S.
      neorickii, S. chmielewskii) species groups were genetically distinct, except for
      S. huaylasense which showed 50% membership proportions in each group. Solanum
      peruvianum and S. corneliomuelleri were not significantly differentiated from
      each other. Many thousands of SNP markers were identified that could potentially
      be used to distinguish pairs of species, including S. peruvianum versus S.
      corneliomuelleri, if they are verified on larger numbers of samples. Diagnostic
      markers will be valuable for delimiting morphologically similar and interfertile
      species in germplasm management. Approximately 12% of the SNPs rejected a genome
      wide test of selective neutrality based on differentiation among species of S.
      peruvianum s.l. These are candidates for more comprehensive studies of
      microevolutionary processes within this species complex.

PMID- 24884692
TI  - Regulatory motifs identified from a maize developmental coexpression network.
AB  - Transcriptional control is an important determinant of plant development, and
      distinct modules of coordinated genes characterize the maize developmental
      transcriptome. Upstream regulatory sequences are often the primary factors that
      control gene expression pattern and abundance. Here, we identify 244 regulatory
      motifs that are significantly enriched within 24 gene expression modules
      previously constructed from transcript abundances of 34,876 Zea mays (maize) gene
      models from embryogenesis to senescence. Within modules, we identify motifs that
      have not been characterized. In addition, we identify motifs similar to
      experimentally verified motifs, and the functions of these motifs overlap with
      predicted module functions. This work demonstrates the power of transcript-level
      coexpression modules to identify both variants of known regulatory motifs and
      novel motifs that control a species' developmental transcriptome.

PMID- 24884693
TI  - Right ventricular dysfunction as an echocardiographic prognostic factor in
      hemodynamically stable patients with acute pulmonary embolism: a meta-analysis.
AB  - BACKGROUND: We investigated whether right ventricular dysfunction (RVD) as
      assessed by echocardiogram can be used as a prognostic factor in hemodynamically
      stable patients with acute pulmonary embolism (PE). Short-term mortality has been
      investigated only in small studies and the results have been controversial.
      METHODS: A PubMed search was conducted using two keywords, "pulmonary embolism"
      and "echocardiogram", for articles published between January 1st 1998 and
      December 31st 2011. Out of 991 articles, after careful review, we found 12
      articles that investigated the implications of RVD as assessed by echocardiogram
      in predicting short-term mortality for hemodynamically stable patients with acute
      PE. We conducted a meta-analysis of these data to identify whether the presence
      of RVD increased short-term mortality. RESULTS: Among 3283 hemodynamically stable
      patients with acute PE, 1223 patients (37.3%) had RVD, as assessed by
      echocardiogram, while 2060 patients (62.7%) had normal right ventricular
      function. Short-term mortality was reported in 167 (13.7%) out of 1223 patients
      with RVD and in 134 (6.5%) out of 2060 patients without RVD. Hemodynamically
      stable patients with acute PE who had RVD as assessed by echocardiogram had a
      2.29-fold increase in short-term mortality (odds ratio 2.29, 95% confidence
      interval 1.61-3.26) compared with patients without RVD. CONCLUSIONS: In
      hemodynamically stable patients with acute PE, RVD as assessed by echocardiogram
      increases short-term mortality by 2.29 times. Consideration should be given to
      obtaining echocardiogram to identify high-risk patients even if they are
      hemodynamically stable.

PMID- 24884694
TI  - Multiple risk factor intervention reduces carotid atherosclerosis in patients
      with type 2 diabetes.
AB  - BACKGROUND: Patients with rapid progression of carotid intima media thickness
      (CIMT) were shown to have a higher future risk for cardiovascular events.The aim
      of this study was to investigate the impact of multiple risk factor intervention
      on CIMT progression and to establish whether new cardiovascular surrogate
      measurements would allow prediction of CIMT changes. MATERIALS AND METHODS: In
      this prospective, open, 2-years study, we included 97 patients with type 2
      diabetes and at least two insufficiently treated cardiovascular risk factors,
      i.e. HbA1c > 7.5% (58 mmol/mol); LDL-cholesterol >3.1 mmol/l or blood pressure
      >140/90 mmHg. Treatment was intensified according to current guidelines over 3
      months with the aim to maintain intensification over 2 years.The primary outcome
      was the change in CIMT after 2 years. We also assessed markers of mechanical and
      biochemical endothelial function and endothelial progenitor cells before and
      after 3 months of treatment intensification. For testing differences between
      before and after multifactorial treatment measurements we used either the paired
      student's t-test or the Wilcoxon signed-rank test, depending on the distribution
      of the data. Additional, explorative statistical data analysis was done on CIMT
      progression building a linear multivariate regression model. RESULTS: Blood
      glucose, lipids and blood pressure significantly improved during the first 3
      months of intensified treatment, which was sustained over the 2-year study
      duration. Mean CIMT significantly decreased from baseline to 2 year (0.883 +/-
      0.120 mm vs. 0.860 +/- 0.130 mm; p = 0.021). None of the investigated surrogate
      measures, however, was able to predict changes in IMT early after treatment
      intensification. CONCLUSIONS: Intensification of risk factor intervention in type
      2 diabetes results in CIMT regression over a period of 2 years. None of the
      biomarkers used including endothelial function parameters or endothelial
      progenitor cells turned out to be useful to predict CIMT changes. TRIAL
      REGISTRATION: Clinical Trial Registration - Unique identifier: NCT00660790.

PMID- 24884695
TI  - The multiplicity of alternative splicing decisions in Caenorhabditis elegans is
      linked to specific intronic regulatory motifs and minisatellites.
AB  - BACKGROUND: Alternative splicing diversifies the pool of messenger RNA molecules
      encoded by individual genes. This diversity is particularly high when multiple
      splicing decisions cause a combinatorial arrangement of several alternate exons.
      We know very little on how the multiple decisions occurring during the maturation
      of single transcripts are coordinated and whether specific sequence elements
      might be involved. RESULTS: Here, the Caenorhabditis elegans genome was surveyed
      in order to identify sequence elements that might play a specific role in the
      regulation of multiple splicing decisions. The introns flanking alternate exons
      in transcripts whose maturation involves multiple alternative splicing decisions
      were compared to those whose maturation involves a single decision. Fifty-eight
      penta-, hexa-, and hepta-meric elements, clustered in 17 groups, were
      significantly over-represented in genes subject to multiple alternative splicing
      decisions. Most of these motifs relate to known splicing regulatory elements and
      appear to be well conserved in the related species Caenorhabditis briggsae. The
      usage of specific motifs is not linked to the gene product function, but rather
      depends on the gene structure, since it is influenced by the distance separating
      the multiple splicing decision sites. Two of these motifs are part of the
      CeRep25B minisatellite, which is also over-represented at the vicinity of
      alternative splicing regions. Most of the remaining motifs are not part of
      repeated sequence elements, but tend to occur in specific heterologous pairs in
      genes subject to multiple alternative splicing decisions. CONCLUSIONS: The
      existence of specific intronic sequence elements linked to multiple alternative
      splicing decisions is intriguing and suggests that these elements might have some
      specialized regulatory role during splicing.

PMID- 24884696
TI  - Prefrontal cortical and striatal transcriptional responses to the reinforcing
      effect of repeated methylphenidate treatment in the spontaneously hypertensive
      rat, animal model of attention-deficit/hyperactivity disorder (ADHD).
AB  - BACKGROUND: Methylphenidate is the most commonly used stimulant drug for the
      treatment of attention-deficit/hyperactivity disorder (ADHD). Research has found
      that methylphenidate is a "reinforcer" and that individuals with ADHD also abuse
      this medication. Nevertheless, the molecular consequences of long-term
      recreational methylphenidate use or abuse in individuals with ADHD are not yet
      fully known. METHODS: Spontaneously hypertensive rats (SHR), the most validated
      and widely used ADHD animal model, were pretreated with methylphenidate (5 mg/kg,
      i.p.) during their adolescence (post-natal day [PND] 42-48) and tested for
      subsequent methylphenidate-induced conditioned place preference (CPP) and self
      administration. Thereafter, the differentially expressed genes in the prefrontal
      cortex (PFC) and striatum of representative methylphenidate-treated SHRs, which
      showed CPP to and self-administration of methylphenidate, were analyzed. RESULTS:
      Genome-wide transcriptome profiling analyses revealed 30 differentially expressed
      genes in the PFC, which include transcripts involved in apoptosis (e.g. S100a9,
      Angptl4, Nfkbia), transcription (Cebpb, Per3), and neuronal plasticity (Homer1,
      Jam2, Asap1). In contrast, 306 genes were differentially expressed in the
      striatum and among them, 252 were downregulated. The main functional categories
      overrepresented among the downregulated genes include those involved in cell
      adhesion (e.g. Pcdh10, Ctbbd1, Itgb6), positive regulation of apoptosis (Perp,
      Taf1, Api5), (Notch3, Nsbp1, Sik1), mitochondrion organization (Prps18c, Letm1,
      Uqcrc2), and ubiquitin-mediated proteolysis (Nedd4, Usp27x, Ube2d2). CONCLUSION:
      Together, these changes indicate methylphenidate-induced neurotoxicity, altered
      synaptic and neuronal plasticity, energy metabolism and ubiquitin-dependent
      protein degradation in the brains of methylphenidate-treated SHRs, which showed
      methylphenidate CPP and self-administration. In addition, these findings may also
      reflect cognitive impairment associated with chronic methylphenidate use as
      demonstrated in preclinical studies. Future studies are warranted to determine
      the clinical significance of the present findings with regard to long-term
      recreational methylphenidate use or abuse in individuals with ADHD.

PMID- 24884697
TI  - EDAR-induced hypohidrotic ectodermal dysplasia: a clinical study on signs and
      symptoms in individuals with a heterozygous c.1072C > T mutation.
AB  - BACKGROUND: Mutations in the EDAR-gene cause hypohidrotic ectodermal dysplasia,
      however, the oral phenotype has been described in a limited number of cases. The
      aim of the present study was to clinically describe individuals with the c.1072C
      > T mutation (p. Arg358X) in the EDAR gene with respect to dental signs and
      saliva secretion, symptoms from other ectodermal structures and to assess
      orofacial function. METHODS: Individuals in three families living in Sweden,
      where some members had a known c.1072C > T mutation in the EDAR gene with an
      autosomal dominant inheritance (AD), were included in a clinical investigation on
      oral signs and symptoms and self-reported symptoms from other ectodermal
      structures (n = 37). Confirmation of the c.1072C > T mutation in the EDAR gene
      were performed by genomic sequencing. Orofacial function was evaluated with NOT
      S. RESULTS: The mutation was identified in 17 of 37 family members. The mean
      number of missing teeth due to agenesis was 10.3 +/- 4.1, (range 4-17) in the
      mutation group and 0.1 +/- 0.3, (range 0-1) in the non-mutation group (p < 0.01).
      All individuals with the mutation were missing the maxillary lateral incisors and
      one or more of the mandibular incisors; and 81.3% were missing all four.
      Stimulated saliva secretion was 0.9 +/- 0.5 ml/min in the mutation group vs 1.7
      +/- 0.6 ml/min in the non-mutation group (p < 0.01). Reduced ability to sweat was
      reported by 82% in the mutation group and by 20% in the non-mutation group (p <
      0.01). The mean NOT-S score was 3.0 +/- 1.9 (range 0-6) in the mutation group and
      1.5 +/- 1.1 (range 0-5) in the non-mutation group (p < 0.01). Lisping was present
      in 56% of individuals in the mutation group. CONCLUSIONS: Individuals with a
      c.1072C > T mutation in the EDAR-gene displayed a typical pattern of congenitally
      missing teeth in the frontal area with functional consequences. They therefore
      have a need for special attention in dental care, both with reference to tooth
      agenesis and low salivary secretion with an increased risk for caries. Sweating
      problems were the most frequently reported symptom from other ectodermal
      structures.

PMID- 24884698
TI  - Deep mRNA sequencing reveals stage-specific transcriptome alterations during
      microsclerotia development in the smoke tree vascular wilt pathogen, Verticillium
      dahliae.
AB  - BACKGROUND: Verticillium dahliae is a soil-borne fungus that causes vascular wilt
      diseases in a wide range of plant hosts. V. dahliae produces multicelled,
      melanized resting bodies, also known as microsclerotia (MS) that can survive for
      years in the soil. The MS are the primary source of infection of the Verticillium
      disease cycle. Thus, MS formation marks an important event in the disease cycle
      of V. dahliae. RESULTS: In this study, next generation sequencing technology of
      RNA-Seq was employed to investigate the global transcriptomic dynamics of MS
      development to identify differential gene expression at several stages of MS
      formation in strain XS11 of V. dahliae, isolated from smoke tree. We observed
      large-scale changes in gene expression during MS formation, such as increased
      expression of genes involved in protein metabolism and carbohydrate metabolism.
      Genes involved in glycolytic pathway and melanin biosynthesis were dramatically
      up-regulated in MS. Cluster analyses revealed increased expression of genes
      encoding products involved in primary metabolism and stress responses throughout
      MS development. Differential expression of ubiquitin-dependent protein catabolism
      and cell death-associated genes during MS development were revealed. Homologs of
      genes located in the lineage-specific (LS) regions of V. dahliae strain VdLs.17,
      were either not expressed or showed low expression. Furthermore, alternative
      splicing (AS) events were analyzed, revealing that over 95.0% AS events involve
      retention of introns (RI). CONCLUSIONS: These data reveal the dynamics of
      transcriptional regulation during MS formation and were used to construct a
      comprehensive high-resolution gene expression map. This map provides a key
      resource for understanding the biology and molecular basis of MS development of
      V. dahliae.

PMID- 24884699
TI  - Long-branch attraction and the phylogeny of true water bugs (Hemiptera:
      Nepomorpha) as estimated from mitochondrial genomes.
AB  - BACKGROUND: Most previous studies of morphological and molecular data have
      consistently supported the monophyly of the true water bugs (Hemiptera:
      Nepomorpha). An exception is a recent study by Hua et al. (BMC Evol Biol 9: 134,
      2009) based on nine nepomorphan mitochondrial genomes. In the analysis of Hua et
      al. (BMC Evol Biol 9: 134, 2009), the water bugs in the group Pleoidea formed the
      sister group to a clade that consisted of Nepomorpha (the remaining true water
      bugs) + Leptopodomorpha (shore bugs) + Cimicomorpha (assassin bugs and relatives)
      + Pentatomomorpha (stink bugs and relatives), thereby suggesting that fully
      aquatic hemipterans evolved independently at least twice. Based on these results,
      Hua et al. (BMC Evol Biol 9: 134, 2009) elevated the Pleoidea to a new
      infraorder, the Plemorpha. RESULTS: Our reanalysis suggests that the lack of
      support for the monophyly of the true water bugs (including Pleoidea) by Hua et
      al. (BMC Evol Biol 9: 134, 2009) likely resulted from inadequate taxon sampling.
      In particular, long-branch attraction (LBA) between the distant outgroup taxa and
      Pleoidea, as well as LBA among taxa in the ingroup, made Nepomorpha appear to be
      polyphyletic. We used three complementary strategies to test and alleviate the
      effects of LBA: (1) the removal of distant outgroups from the analysis; (2) the
      addition of closely related outgroups; and (3) the addition of a mitochondrial
      genome from a second family of Pleoidea. We also performed likelihood-ratio tests
      to examine the support for monophyly of Nepomorpha with different combinations of
      taxa included in the analysis. Furthermore, we found that specimens of
      Helotrephes sp. were misidentified as Paraplea frontalis (Fieber, 1844) by Hua et
      al. (BMC Evol Biol 9: 134, 2009). CONCLUSIONS: All analyses that included the
      addition of more taxa significantly and consistently supported the placement of
      Pleoidea within the Nepomorpha (i.e., supported the monophyly of the traditional
      true water bugs). Our analyses further support a close relationship between
      Notonectoidea and Pleoidea within Nepomorpha, and the superfamilies Nepoidea,
      Ochteroidea, Naucoroidea, and Pleoidea are resolved as monophyletic in all trees
      with strong support. Our results also confirmed that monophyly of Nepomorpha
      clearly is not refuted by the mitochondrial genome data.

PMID- 24884700
TI  - Mesoniviruses are mosquito-specific viruses with extensive geographic
      distribution and host range.
AB  - BACKGROUND: The family Mesoniviridae (order Nidovirales) comprises of a group of
      positive-sense, single-stranded RNA ([+]ssRNA) viruses isolated from mosquitoes.
      FINDINGS: Thirteen novel insect-specific virus isolates were obtained from
      mosquitoes collected in Indonesia, Thailand and the USA. By electron microscopy,
      the virions appeared as spherical particles with a diameter of ~50 nm. Their
      20,129 nt to 20,777 nt genomes consist of positive-sense, single-stranded RNA
      with a poly-A tail. Four isolates from Houston, Texas, and one isolate from Java,
      Indonesia, were identified as variants of the species Alphamesonivirus-1 which
      also includes Nam Dinh virus (NDiV) from Vietnam and Cavally virus (CavV) from
      Cote d'Ivoire. The eight other isolates were identified as variants of three new
      mesoniviruses, based on genome organization and pairwise evolutionary distances:
      Karang Sari virus (KSaV) from Java, Bontag Baru virus (BBaV) from Java and
      Kalimantan, and Kamphaeng Phet virus (KPhV) from Thailand. In comparison with
      NDiV, the three new mesoniviruses each contained a long insertion (180 - 588 nt)
      of unknown function in the 5' region of ORF1a, which accounted for much of the
      difference in genome size. The insertions contained various short imperfect
      repeats and may have arisen by recombination or sequence duplication.
      CONCLUSIONS: In summary, based on their genome organizations and phylogenetic
      relationships, thirteen new viruses were identified as members of the family
      Mesoniviridae, order Nidovirales. Species demarcation criteria employed
      previously for mesoniviruses would place five of these isolates in the same
      species as NDiV and CavV (Alphamesonivirus-1) and the other eight isolates would
      represent three new mesonivirus species (Alphamesonivirus-5, Alphamesonivirus-6
      and Alphamesonivirus-7). The observed spatiotemporal distribution over widespread
      geographic regions and broad species host range in mosquitoes suggests that
      mesoniviruses may be common in mosquito populations worldwide.

PMID- 24884701
TI  - WinHAP2: an extremely fast haplotype phasing program for long genotype sequences.
AB  - BACKGROUND: The haplotype phasing problem tries to screen for phenotype
      associated genomic variations from millions of candidate data. Most of the
      current computer programs handle this problem with high requirements of computing
      power and memory. By replacing the computation-intensive step of constructing the
      maximum spanning tree with a heuristics of estimated initial haplotype, we
      released the WinHAP algorithm version 1.0, which outperforms the other algorithms
      in terms of both running speed and overall accuracy. RESULTS: This work further
      speeds up the WinHAP algorithm to version 2.0 (WinHAP2) by utilizing the divide
      and-conquer strategy and the OpenMP parallel computing mode. WinHAP2 can phase
      500 genotypes with 1,000,000 SNPs using just 12.8 MB in memory and 2.5 hours on a
      personal computer, whereas the other programs require unacceptable memory or
      running times. The parallel running mode further improves WinHAP2's running speed
      with several orders of magnitudes, compared with the other programs, including
      Beagle, SHAPEIT2 and 2SNP. CONCLUSIONS: WinHAP2 is an extremely fast haplotype
      phasing program which can handle a large-scale genotyping study with any number
      of SNPs in the current literature and at least in the near future.

PMID- 24884702
TI  - A description of the hepatitis B virus genomic background in a high-prevalence
      area in China.
AB  - BACKGROUND: Hepatitis B (HB) is an important disease worldwide. Almost 350
      million people are positive for Hepatitis B virus surface antigen (HBsAg), and
      one-third of them live in China. According to a nation-wide serosurvey in China
      in 2006, the prevalence of HBsAg was higher in Northwest China than in other
      areas. However, the epidemic HBV strains in this area are poorly studied.
      RESULTS: In this study, 242 complete hepatitis B virus (HBV) genome sequences
      were obtained from HBV asymptomatic carriers in major cities of Northwest China.
      The 242 HBV sequences clustered into genotypes B, C and D. Through comparison of
      the genotype consensus sequences, 158 genotype-dependent positions were observed
      in P, S and X ORFs. Clinically relevant mutation screening in this study revealed
      that no HBV antiviral drug resistance mutations were observed and the vaccination
      failure mutations were heavily underrepresented. CONCLUSIONS: The role of
      genotype D strains in HBV prevalence should not be ignored in Northwest China.
      Due to low prevalence of vaccination failure mutations, it can be inferred that
      the genotype B, C and D strains in Northwest China may have less likelihood of
      vaccine escape.

PMID- 24884703
TI  - Role of inflammation in previously untreated macular edema with branch retinal
      vein occlusion.
AB  - BACKGROUND: The association of inflammatory factors and the aqueous flare value
      with macular edema in branch retinal vein occlusion (BRVO) patients remains
      unclear. The relationship between the aqueous flare value and the vitreous fluid
      levels of vascular endothelial growth factor (VEGF), interleukin (IL)-6, monocyte
      chemotactic protein (MCP)-1, soluble intercellular adhesion molecule 1 (sICAM-1),
      and soluble VEGF receptor-2 (sVEGFR-2) was evaluated to investigate the role of
      inflammation in BRVO associated with macular edema. Aqueous flare values and the
      vitreous levels of VEGF, IL-6, MCP-1, sICAM-1, and sVEGFR-2 were compared between
      previously untreated patients with BRVO and patients with macular hole (MH).
      METHODS: Vitreous samples were obtained from 45 patients during vitreoretinal
      surgery (28 patients with BRVO and 17 with MH), and the levels of VEGF, IL-6, MCP
      1, sICAM-1, and sVEGFR-2 were measured by enzyme-linked immunosorbent assay.
      Retinal ischemia was evaluated by measuring the area of capillary non-perfusion
      using fluorescein angiography and the Scion Image program. Aqueous flare values
      were measured with a laser flare meter and macular edema was examined by optical
      coherence tomography. RESULTS: The median aqueous flare value was significantly
      higher in the BRVO group (12.1 photon counts/ms) than in the MH group (4.5 photon
      counts/ms, P < 0.001). There were significant correlations between the aqueous
      flare value and the vitreous levels of VEGF, IL-6, MCP-1, and sICAM-1 in the BRVO
      group (rho = 0.54, P = 0.005; rho = 0.56, P = 0.004; rho = 0.52, P = 0.006; and
      rho = 0.47, P = 0.015, respectively). The aqueous flare value was also
      significantly correlated with the foveal thickness in the BRVO group (rho = 0.40,
      P = 0.037). CONCLUSIONS: Inflammation may induce an increase of vascular
      permeability and disrupt the blood-aqueous barrier via release of inflammatory
      factors (VEGF, IL-6, MCP-1, and sICAM-1) in BRVO patients with macular edema.

PMID- 24884704
TI  - The DREEM, part 2: psychometric properties in an osteopathic student population.
AB  - BACKGROUND: The Dundee Ready Educational Environment Measure (DREEM) is widely
      used to assess the educational environment in health professional education
      programs. A number of authors have identified issues with the psychometric
      properties of the DREEM. Part 1 of this series of papers presented the
      quantitative data obtained from the DREEM in the context of an Australian
      osteopathy program. The present study used both classical test theory and item
      response theory to investigate the DREEM psychometric properties in an osteopathy
      student population. METHODS: Students in the osteopathy program at Victoria
      University (Melbourne, Australia) were invited to complete the DREEM and a
      demographic questionnaire at the end of the 2013 teaching year (October 2013).
      Data were analysed using both classical test theory (confirmatory factor
      analysis) and item response theory (Rasch analysis). RESULTS: Confirmatory factor
      analysis did not demonstrate model fit for the original 5-factor DREEM subscale
      structure. Rasch analysis failed to identify a unidimensional model fit for the
      50-item scale, however model fit was achieved for each of the 5 subscales
      independently. A 12-item version of the DREEM was developed that demonstrated
      good fit to the Rasch model, however, there may be an issue with the targeting of
      this scale given the mean item-person location being greater than 1. CONCLUSIONS:
      Given that the full 50-item scale is not unidimensional; those using the DREEM
      should avoid calculating a total score for the scale. The 12-item 'short-form' of
      the DREEM warrants further investigation as does the subscale structure. To
      confirm the reliability of the DREEM, as a measure to evaluate the
      appropriateness of the educational environment of health professionals, further
      work is required to establish the psychometric properties of the DREEM, with a
      range of student populations.

PMID- 24884705
TI  - Changes in vitamin and mineral supplement use after breast cancer diagnosis in
      the Pathways Study: a prospective cohort study.
AB  - BACKGROUND: Vitamin and mineral supplement use after a breast cancer diagnosis is
      common and controversial. Dosages used and the timing of initiation and/or
      discontinuation of supplements have not been clearly described. METHODS: We
      prospectively examined changes in use of 17 vitamin/mineral supplements in the
      first six months following breast cancer diagnosis among 2,596 members (28% non
      white) of Kaiser Permanente Northern California. We used multivariable logistic
      regression to examine demographic, clinical, and lifestyle predictors of
      initiation and discontinuation. RESULTS: Most women used vitamin/mineral
      supplements before (84%) and after (82%) diagnosis, with average doses far in
      excess of Institute of Medicine reference intakes. Over half (60.2%) reported
      initiating a vitamin/mineral following diagnosis, 46.3% discontinuing a
      vitamin/mineral, 65.6% using a vitamin/mineral continuously, and only 7.2% not
      using any vitamin/mineral supplement before or after diagnosis. The most commonly
      initiated supplements were calcium (38.2%), vitamin D (32.01%), vitamin B6
      (12.3%) and magnesium (11.31%); the most commonly discontinued supplements were
      multivitamins (17.14%), vitamin C (15.97%) and vitamin E (45.62%). Higher
      education, higher intake of fruits/vegetables, and receipt of chemotherapy were
      associated with initiation (p-values <0.05). Younger age and breast-conserving
      surgery were associated with discontinuation (p-values <0.05). CONCLUSIONS: In
      this large cohort of ethnically diverse breast cancer patients, high numbers of
      women used vitamin/mineral supplements in the 6 months following breast cancer
      diagnosis, often at high doses and in combination with other supplements. The
      immediate period after diagnosis is a critical time for clinicians to counsel
      women on supplement use.

PMID- 24884706
TI  - Effective filtering strategies to improve data quality from population-based
      whole exome sequencing studies.
AB  - BACKGROUND: Genotypes generated in next generation sequencing studies contain
      errors which can significantly impact the power to detect signals in common and
      rare variant association tests. These genotyping errors are not explicitly
      filtered by the standard GATK Variant Quality Score Recalibration (VQSR) tool and
      thus remain a source of errors in whole exome sequencing (WES) projects that
      follow GATK's recommended best practices. Therefore, additional data filtering
      methods are required to effectively remove these errors before performing
      association analyses with complex phenotypes. Here we empirically derive
      thresholds for genotype and variant filters that, when used in conjunction with
      the VQSR tool, achieve higher data quality than when using VQSR alone. RESULTS:
      The detailed filtering strategies improve the concordance of sequenced genotypes
      with array genotypes from 99.33% to 99.77%; improve the percent of discordant
      genotypes removed from 10.5% to 69.5%; and improve the Ti/Tv ratio from 2.63 to
      2.75. We also demonstrate that managing batch effects by separating samples based
      on different target capture and sequencing chemistry protocols results in a final
      data set containing 40.9% more high-quality variants. In addition, imputation is
      an important component of WES studies and is used to estimate common variant
      genotypes to generate additional markers for association analyses. As such, we
      demonstrate filtering methods for imputed data that improve genotype concordance
      from 79.3% to 99.8% while removing 99.5% of discordant genotypes. CONCLUSIONS:
      The described filtering methods are advantageous for large population-based WES
      studies designed to identify common and rare variation associated with complex
      diseases. Compared to data processed through standard practices, these strategies
      result in substantially higher quality data for common and rare association
      analyses.

PMID- 24884707
TI  - Psychosocial work conditions and quality of life among primary health care
      employees: a cross sectional study.
AB  - BACKGROUND: Workers in Primary Health Care are often exposed to stressful
      conditions at work. This study investigated the association between adverse
      psychosocial work conditions and poor quality of life among Primary Health Care
      workers. METHODS: This cross-sectional study included all 797 Primary Health Care
      workers of a medium-sized city, Brazil: doctors, nurses, nursing technicians and
      nursing assistants, dentists, oral health technicians, and auxiliary oral
      hygienists, and community health workers. Data were collected by interviews.
      Quality of life was assessed using the WHOQOL-BREF; general quality of life, as
      well as the physical, psychological, social and environmental domains were
      considered, with scores from 0 to 100. Higher scores indicate a better quality of
      life. Poor quality of life was defined by the lowest quartiles of the WHOQOL
      score distributions for each of the domains. Adverse psychosocial work conditions
      were investigated by the Effort-Reward Imbalance model. Associations were
      verified using multiple logistic regression. RESULTS: Poor quality of life was
      observed in 117 (15.4%) workers. Workers with imbalanced effort-reward (high
      effort/low reward) had an increased probability of general poor quality of life
      (OR = 1.91; 1.07-3.42), and in the physical (OR = 1.62; 1.02-2.66), and
      environmental (OR = 2.39; 1.37-4.16) domains; those with low effort/low reward
      demonstrated a greater probability of poor quality of life in the social domain
      (OR = 1.82; 1.00-3.30). Workers with overcommitment at work had an increased
      likelihood of poor quality of life in the physical (OR = 1.55, 1.06-2.26) and
      environmental (OR = 1.69; 1.08-2.65) domains. These associations were independent
      of individual characteristics, job characteristics, lifestyle, perception of
      general health, or psychological and biological functions. CONCLUSIONS: There is
      an association between adverse psychosocial work conditions and poor quality of
      life among Primary Health Care workers.

PMID- 24884709
TI  - Angelica Sinensis promotes myotube hypertrophy through the PI3K/Akt/mTOR pathway.
AB  - BACKGROUND: Angelica Sinensis (AS), a folk medicine, has long been used in
      ergogenic aids for athletes, but there is little scientific evidence supporting
      its effects. We investigated whether AS induces hypertrophy in myotubes through
      the phosphatidylinositol 3-kinase (PI3K)/Akt (also termed PKB)/mammalian target
      of the rapamycin (mTOR) pathway. METHODS: An in vitro experiment investigating
      the induction of hypertrophy in myotubes was conducted. To investigate whether AS
      promoted the hypertrophy of myotubes, an established in vitro model of myotube
      hypertrophy with and without AS was used and examined using microscopic images.
      The role of the PI3K/Akt/mTOR signaling pathway in AS-induced myotube hypertrophy
      was evaluated. Two inhibitors, wortmannin (an inhibitor of PI3K) and rapamycin
      (an inhibitor of mTOR), were used. RESULT: The results revealed that the myotube
      diameters in the AS-treated group were significantly larger than those in the
      untreated control group (P < 0.05). Wortmannin and rapamycin inhibited AS-induced
      hypertrophy. Furthermore, AS increased Akt and mTOR phosphorylation through the
      PI3K pathway and induced myotube hypertrophy. CONCLUSION: The results confirmed
      that AS induces hypertrophy in myotubes through the PI3K/Akt/mTOR pathway.

PMID- 24884708
TI  - KNOW-CKD (KoreaN cohort study for Outcome in patients With Chronic Kidney
      Disease): design and methods.
AB  - BACKGROUND: The progression and complications of chronic kidney disease should
      differ depending on the cause (C), glomerular filtration rate category (G), and
      albuminuria (A). The KNOW-CKD (KoreaN Cohort Study for Outcome in Patients With
      Chronic Kidney Disease), which is a prospective cohort study, enrolls subjects
      with chronic kidney disease stages 1 to 5 (predialysis). METHODS/DESIGN: Nine
      nephrology centers in major university hospitals throughout Korea will enroll
      approximately 2,450 adults with chronic kidney disease over a 5-year period from
      2011 to 2015. The participating individuals will be monitored for approximately
      10 years until death or until end-stage renal disease occurs. The subjects will
      be classified into subgroups based on the following specific causes of chronic
      kidney disease: glomerulonephritis, diabetic nephropathy, hypertensive
      nephropathy, polycystic kidney disease, and others. The eligible subjects will be
      evaluated at baseline for socio-demographic information, detailed personal/family
      history, office BP, quality of life, and health behaviors. After enrollment in
      the study, thorough assessments, including laboratory tests, cardiac evaluation
      and radiologic imaging, will be performed according to the standardized protocol.
      The biospecimen samples will be collected regularly. A renal event is defined by
      >50% decrease in estimated GFR (eGFR) from the baseline values, doubling of serum
      creatinine, or end-stage renal disease. The primary composite outcome consists of
      renal events, cardiovascular events, and death. As of September 2013, 1,470 adult
      chronic kidney disease subjects were enrolled in the study, including 543
      subjects with glomerulonephritis, 317 with diabetic nephropathy, 294 with
      hypertensive nephropathy and 249 with polycystic kidney disease. DISCUSSION: As
      the first large-scale chronic kidney disease cohort study to be established and
      maintained longitudinally for up to 10 years, the KNOW-CKD will help to clarify
      the natural course, complication profiles, and risk factors of Asian populations
      with chronic kidney disease. TRIAL REGISTRATION: No. NCT01630486 at
      http://www.clinicaltrials.gov.

PMID- 24884710
TI  - Regulation of ACVR1 and ID2 by cell-secreted exosomes during follicle maturation
      in the mare.
AB  - BACKGROUND: Ovarian follicle growth and maturation requires extensive
      communication between follicular somatic cells and oocytes. Recently,
      intercellular cell communication was described involving cell-secreted vesicles
      called exosomes (50-150 nm), which contain miRNAs and protein, and have been
      identified in ovarian follicular fluid. The goal of this study was to identify a
      possible role of exosomes in follicle maturation. METHODS: Follicle contents were
      collected from mares at mid-estrous (~35 mm, before induction of follicular
      maturation) and pre-ovulatory follicles (30-34 h after induction of follicular
      maturation). A real time PCR screen was conducted to reveal significant
      differences in the presence of exosomal miRNAs isolated from mid-estrous and pre
      ovulatory follicles, and according to bioinformatics analysis these exosomal
      miRNAs are predicted to target members belonging to the TGFB superfamily,
      including ACVR1 and ID2. Granulosa cells from pre-ovulatory follicles were
      cultured and treated with exosomes isolated from follicular fluid. Changes in
      mRNA and protein were measured by real time PCR and Western blot. RESULTS: ACVR1
      mRNA and protein was detected in granulosa cells at mid-estrous and pre-ovulatory
      stages, and real time PCR analysis revealed significantly lower levels of ID2 (an
      ACVR1 target gene) in granulosa cells from pre-ovulatory follicles. Exposure to
      exosomes from follicular fluid of mid-estrous follicles decreased ID2 levels in
      granulosa cells. Moreover, exosomes isolated from mid-estrous and pre-ovulatory
      follicles contain ACVR1 and miR-27b, miR-372, and miR-382 (predicted regulators
      of ACVR1 and ID2) were capable of altering ID2 levels in pre-ovulatory granulosa
      cells. CONCLUSIONS: These data indicate that exosomes isolated from follicular
      fluid can regulate members of the TGFB/BMP signaling pathway in granulosa cells,
      and possibly play a role in regulating follicle maturation.

PMID- 24884711
TI  - No consensus on gestational diabetes mellitus screening regimes in Sweden:
      pregnancy outcomes in relation to different screening regimes 2011 to 2012, a
      cross-sectional study.
AB  - BACKGROUND: Although associated adverse pregnancy outcomes, no international or
      Swedish consensus exists that identifies a cut-off value or what screening method
      to use for definition of gestational diabetes mellitus. This study investigates
      the following: i) guidelines for screening of GDM; ii) background and risk
      factors for GDM and selection to OGTT; and iii) pregnancy outcomes in relation to
      GDM, screening regimes and levels of OGTT 2 hour glucose values. METHODS: This
      cross-sectional and population-based study uses data from the Swedish Maternal
      Health Care Register (MHCR) (2011 and 2012) combined with guidelines for GDM
      screening (2011-2012) from each Maternal Health Care Area (MHCA) in Sweden. The
      sample consisted of 184,183 women: 88,140 in 2011 and 96,043 in 2012. Chi-square
      and two independent samples t-tests were used. Univariate and multivariate
      logistic regression analyses were performed. RESULTS: Four screening regimes of
      oral glucose tolerance test (OGTT) (75 g of glucose) were used: A) universal
      screening with a 2-hour cut-off value of 10.0 mmol/L; B) selective screening with
      a 2-hour cut-off value of 8.9 mmol/L; C) selective screening with a 2-hour cut
      off value of 10.0 mmol/L; and D) selective screening with a 2-hour cut-off value
      of 12.2 mmol/L. The highest prevalence of GDM (2.9%) was found with a 2-hour cut
      off value of 8.9 mmol/L when selective screening was applied. Unemployment and
      low educational level were associated with an increased risk of GDM. The OR was
      4.14 (CI 95%: 3.81-4.50) for GDM in obese women compared to women with BMI <30
      kg/m2. Women with non-Nordic origin presented a more than doubled risk for GDM
      compared to women with Nordic origin (OR = 2.24; CI 95%: 2.06-2.43). Increasing
      OGTT values were associated with increasing risks of adverse pregnancy outcomes.
      CONCLUSIONS: There was no consensus regarding screening regimes for GDM from 2011
      through 2012 when four different regimes were applied in Sweden. Increasing
      levels of OGTT 2-hour glucose values were strongly associated with adverse
      pregnancy outcomes. Based on these findings, we suggest that Sweden adopts the
      recent recommendations of the International Association of Diabetes and Pregnancy
      Study Group (IADPSG) concerning the performance of OGTT and the diagnostic
      criteria for GDM.

PMID- 24884712
TI  - Missed case of sinus venosus atrial septal defect post coronary artery bypass
      grafting.
AB  - We report a case of a 41-year-old Indian man who initially underwent an emergency
      coronary artery bypass grafting surgery (CABG) after presenting with an
      anterolateral myocardial infarction.Post-operatively he developed progressively
      worsening symptoms of right heart failure with increasing abdominal distension
      and lower limb swelling. Clinically, the patient was in NYHA class 4 heart
      failure.He was admitted multiple times for the treatment of his heart failure,
      which was recalcitrant to diuretic therapy.He subsequently underwent an MRI scan,
      which revealed near transmural myocardial infarction involving mainly the left
      side of the heart. The right atrium and ventricle were grossly dilated, with
      moderate to severe right ventricular systolic dysfunction. A sinus venosus atrial
      septal defect with right-sided partial anomalous pulmonary venous drainange
      (PAPVD) was noted. He subsequently underwent surgery to repair the sinus venosus
      atrial septal defect (ASD) as well as re-route the PAPVD to the left atrium (LA).
      He was discharged on post-operative day 19 with oral diuretics.On follow-up at 1
      month, the patient's symptoms had resolved and his clinical status corresponded
      to NYHA class 1-2. 

PMID- 24884714
TI  - Using life history narratives to educate staff members about personhood in
      assisted living.
AB  - Oral life history narratives are a promising method to promote person-centered
      values of personhood and belonging. This project used resident oral history
      interviews to educate staff members in an assisted-living setting about
      personhood. A single group pre-post test design evaluated impacts on 37 staff
      members to assess their use of resident videotaped oral history interviews and
      impacts on their perceived knowledge of residents. Perceived knowledge of
      residents declined (p = .003) between pretest and posttest. Older staff members
      were less likely to view a video. Staff members are interested in resident oral
      history biographies and identify them as helpful for delivering care. Oral
      history methods might provide an opportunity for staff members to promote
      personhood by allowing them to expand their understanding of resident
      preferences, values, and experiences. 

PMID- 24884713
TI  - Functional characterization of a Penicillium chrysogenum mutanase gene induced
      upon co-cultivation with Bacillus subtilis.
AB  - BACKGROUND: Microbial gene expression is strongly influenced by environmental
      growth conditions. Comparison of gene expression under different conditions is
      frequently used for functional analysis and to unravel regulatory networks,
      however, gene expression responses to co-cultivation with other microorganisms, a
      common occurrence in nature, is rarely studied under laboratory conditions. To
      explore cellular responses of the antibiotic-producing fungus Penicillium
      chrysogenum to prokaryotes, the present study investigates its transcriptional
      responses during co-cultivation with Bacillus subtilis. RESULTS: Steady-state
      glucose-limited chemostats of P. chrysogenum grown under penillicin-non-producing
      conditions were inoculated with B. subtilis. Physiological and transcriptional
      responses of P. chrysogenum in the resulting mixed culture were monitored over 72
      h. Under these conditions, B. subtilis outcompeted P. chrysogenum, as reflected
      by a three-fold increase of the B. subtilis population size and a two-fold
      reduction of the P. chrysogenum biomass concentration. Genes involved in the
      penicillin pathway and in synthesis of the penicillin precursors and side-chain
      were unresponsive to the presence of B. subtilis. Moreover, Penicillium
      polyketide synthase and nonribosomal peptide synthase genes were either not
      expressed or down-regulated. Among the highly responsive genes, two putative
      alpha-1,3 endoglucanase (mutanase) genes viz Pc12g07500 and Pc12g13330 were
      upregulated by more than 15-fold and 8-fold, respectively. Measurement of enzyme
      activity in the supernatant of mixed culture confirmed that the co-cultivation
      with B. subtilis induced mutanase production. Mutanase activity was neither
      observed in pure cultures of P. chrysogenum or B. subtilis, nor during exposure
      of P. chrysogenum to B. subtilis culture supernatants or heat-inactivated B.
      subtilis cells. However, mutanase production was observed in cultures of P.
      chrysogenum exposed to filter-sterilized supernatants of mixed cultures of P.
      chrysogenum and B. subtilis. Heterologous expression of Pc12g07500 and Pc12g13330
      genes in Saccharomyces cerevisiae confirmed that Pc12g07500 encoded an active
      alpha-1,3 endoglucanase. CONCLUSION: Time-course transcriptional profiling of P.
      chrysogenum revealed differentially expressed genes during co-cultivation with B.
      subtilis. Penicillin production was not induced under these conditions. However,
      induction of a newly characterized P. chrysogenum gene encoding alpha-1,3
      endoglucanase may enhance the efficacy of fungal antibiotics by degrading
      bacterial exopolysaccharides.

PMID- 24884716
TI  - Validation of reference genes for gene expression analysis in olive (Olea
      europaea) mesocarp tissue by quantitative real-time RT-PCR.
AB  - BACKGROUND: Gene expression analysis using quantitative reverse transcription PCR
      (qRT-PCR) is a robust method wherein the expression levels of target genes are
      normalised using internal control genes, known as reference genes, to derive
      changes in gene expression levels. Although reference genes have recently been
      suggested for olive tissues, combined/independent analysis on different cultivars
      has not yet been tested. Therefore, an assessment of reference genes was required
      to validate the recent findings and select stably expressed genes across
      different olive cultivars. RESULTS: A total of eight candidate reference genes
      [glyceraldehyde 3-phosphate dehydrogenase (GAPDH), serine/threonine-protein
      phosphatase catalytic subunit (PP2A), elongation factor 1 alpha (EF1-alpha),
      polyubiquitin (OUB2), aquaporin tonoplast intrinsic protein (TIP2), tubulin alpha
      (TUBA), 60S ribosomal protein L18-3 (60S RBP L18-3) and polypyrimidine tract
      binding protein homolog 3 (PTB)] were chosen based on their stability in olive
      tissues as well as in other plants. Expression stability was examined by qRT-PCR
      across 12 biological samples, representing mesocarp tissues at various
      developmental stages in three different olive cultivars, Barnea, Frantoio and
      Picual, independently and together during the 2009 season with two software
      programs, GeNorm and BestKeeper. Both software packages identified GAPDH, EF1
      alpha and PP2A as the three most stable reference genes across the three
      cultivars and in the cultivar, Barnea. GAPDH, EF1-alpha and 60S RBP L18-3 were
      found to be most stable reference genes in the cultivar Frantoio while 60S RBP
      L18-3, OUB2 and PP2A were found to be most stable reference genes in the cultivar
      Picual. CONCLUSIONS: The analyses of expression stability of reference genes
      using qRT-PCR revealed that GAPDH, EF1-alpha, PP2A, 60S RBP L18-3 and OUB2 are
      suitable reference genes for expression analysis in developing Olea europaea
      mesocarp tissues, displaying the highest level of expression stability across
      three different olive cultivars, Barnea, Frantoio and Picual, however the
      combination of the three most stable reference genes do vary amongst individual
      cultivars. This study will provide guidance to other researchers to select
      reference genes for normalization against target genes by qPCR across tissues
      obtained from the mesocarp region of the olive fruit in the cultivars, Barnea,
      Frantoio and Picual.

PMID- 24884715
TI  - Combined targeting of TGF-beta1 and integrin beta3 impairs lymph node metastasis
      in a mouse model of non-small-cell lung cancer.
AB  - BACKGROUND: Transforming Growth Factor beta (TGF-beta) acts as a tumor suppressor
      early in carcinogenesis but turns into tumor promoter in later disease stages. In
      fact, TGF-beta is a known inducer of integrin expression by tumor cells which
      contributes to cancer metastatic spread and TGF-beta inhibition has been shown to
      attenuate metastasis in mouse models. However, carcinoma cells often become
      refractory to TGF-beta-mediated growth inhibition. Therefore identifying patients
      that may benefit from anti-TGF-beta therapy requires careful selection. METHODS:
      We performed in vitro analysis of the effects of exposure to TGF-beta in NSCLC
      cell chemotaxis and adhesion to lymphatic endothelial cells. We also studied in
      an orthotopic model of NSCLC the incidence of metastases to the lymph nodes after
      inhibition of TGF-beta signaling, beta3 integrin expression or both. RESULTS: We
      offer evidences of increased beta3-integrin dependent NSCLC adhesion to lymphatic
      endothelium after TGF-beta exposure. In vivo experiments show that targeting of
      TGF-beta and beta3 integrin significantly reduces the incidence of lymph node
      metastasis. Even more, blockade of beta3 integrin expression in tumors that did
      not respond to TGF-beta inhibition severely impaired the ability of the tumor to
      metastasize towards the lymph nodes. CONCLUSION: These findings suggest that lung
      cancer tumors refractory to TGF-beta monotherapy can be effectively treated using
      dual therapy that combines the inhibition of tumor cell adhesion to lymphatic
      vessels with stromal TGF-beta inhibition.

PMID- 24884717
TI  - Cost-effectiveness of enzyme replacement therapy with alglucosidase alfa in
      classic-infantile patients with Pompe disease.
AB  - BACKGROUND: Infantile Pompe disease is a rare metabolic disease. Patients
      generally do not survive the first year of life. Enzyme replacement therapy (ERT)
      has proven to have substantial effects on survival in infantile Pompe disease.
      However, the costs of therapy are very high. In this paper, we assess the cost
      effectiveness of enzyme replacement therapy in infantile Pompe disease. METHODS:
      A patient simulation model was used to compare costs and effects of ERT with
      costs of effects of supportive therapy (ST). The model was filled with data on
      survival, quality of life and costs. For both arms of the model, data on survival
      were obtained from international literature. In addition, survival as observed
      among 20 classic-infantile Dutch patients, who all received ERT, was used.
      Quality of life was measured using the EQ-5D and assumed to be the same in both
      treatment groups. Costs included the costs of ERT (which depend on a child's
      weight), infusions, costs of other health care utilization, and informal care. A
      lifetime time horizon was used, with 6-month time cycles. RESULTS: Life
      expectancy was significantly longer in the ERT group than in the ST group. On
      average, ST receiving patients were modelled not to survive the first half year
      of life; whereas the life expectancy in the ERT patients was modelled to be
      almost 14 years. Lifetime incremental QALYs were 6.8. Incremental costs were
      estimated to be ? 7.0 million, which primarily consisted of treatment costs
      (95%). The incremental costs per QALY were estimated to be ? 1.0 million (range
      sensitivity analyses: ? 0.3 million - ? 1.3 million). The incremental cost per
      life year gained was estimated to be ? 0.5 million. CONCLUSIONS: The incremental
      costs per QALY ratio is far above the conventional threshold values. Results from
      univariate and probabilistic sensitivity analyses showed the robustness of the
      results.

PMID- 24884718
TI  - Genome instability in blood cells of a BRCA1+ breast cancer family.
AB  - BACKGROUND: BRCA1 plays an essential role in maintaining genome stability.
      Inherited BRCA1 germline mutation (BRCA1+) is a determined genetic predisposition
      leading to high risk of breast cancer. While BRCA1+ induces breast cancer by
      causing genome instability, most of the knowledge is known about somatic genome
      instability in breast cancer cells but not germline genome instability. METHODS:
      Using the exome-sequencing method, we analyzed the genomes of blood cells in a
      typical BRCA1+ breast cancer family with an exon 13-duplicated founder mutation,
      including six breast cancer-affected and two breast cancer unaffected members.
      RESULTS: We identified 23 deleterious mutations in the breast cancer-affected
      family members, which are absent in the unaffected members. Multiple mutations
      damaged functionally important and breast cancer-related genes, including
      transcriptional factor BPTF and FOXP1, ubiquitin ligase CUL4B, phosphorylase
      kinase PHKG2, and nuclear receptor activator SRA1. Analysis of the mutations
      between the mothers and daughters shows that most mutations were germline
      mutation inherited from the ancestor(s) while only a few were somatic mutation
      generated de novo. CONCLUSION: Our study indicates that BRCA1+ can cause genome
      instability with both germline and somatic mutations in non-breast cells.

PMID- 24884719
TI  - Recurrent paratyphoid fever A co-infected with hepatitis A reactivated chronic
      hepatitis B.
AB  - We report here a case of recurrent paratyphoid fever A with hepatitis A co
      infection in a patient with chronic hepatitis B. A 26-year-old male patient, who
      was a hepatitis B virus carrier, was co-infected with Salmonella enterica serovar
      Paratyphi A and hepatitis A virus. The recurrence of the paratyphoid fever may be
      ascribed to the coexistence of hepatitis B, a course of ceftriaxone plus
      levofloxacin that was too short and the insensitivity of paratyphoid fever A to
      levofloxacin. We find that an adequate course and dose of ceftriaxone is a better
      strategy for treating paratyphoid fever. Furthermore, the co-infection of
      paratyphoid fever with hepatitis A may stimulate cellular immunity and break
      immunotolerance. Thus, the administration of the anti-viral agent entecavir may
      greatly improve the prognosis of this patient with chronic hepatitis B, and the
      episodes of paratyphoid fever and hepatitis A infection prompt the use of timely
      antiviral therapy.

PMID- 24884720
TI  - Social participation in patients with multiple sclerosis: correlations between
      disability and economic burden.
AB  - BACKGROUND: Economic costs related to treatment of multiple sclerosis (MS) must
      be justified by health state, quality of life (QOL) and social participation
      improvement. This study aims to describe correlations between social
      participation, economic costs, utility and MS-specific QOL in a sample of
      patients with MS (pwMS). METHODS: We interviewed 42 pwMS receiving natalizumab
      and collected clinical data, direct medical costs, productivity loss, utility
      (EQ5D-VAS), MS-specific QOL (SEP-59), social participation with the Impact on
      Participation and Autonomy questionnaire (IPA). We performed descriptive and
      correlation analyses. RESULTS: 41 pwMS, with a mean Expanded Disability Status
      Scale (EDSS) score of 4.0, completed questionnaires. Mean annual global cost per
      patient was 68448 +/-33374 Euros and increased with EDSS (r = 0.644), utility (r
      = -0.456) and IPA (r = 0.519-0.671) worsening. Mean utility was 0.52 +/- 0.28.
      Correlations between IPA and QOL (EQ5D-VAS or SEP-59) were observed (r = -0.53 to
      -0.78). Association between QOL and EDSS was smaller (EQ5D-VAS) or absent.
      Productivity losses were poorly correlated to EDSS (r = 0.375). CONCLUSION:
      Moderate to strong correlations of social participation with clinical status
      (EDSS), QOL, utility and economic costs encourage exploring better these links in
      larger cohorts. The stronger correlation between social participation and QOL
      than between EDSS and QOL needs to be confirmed.

PMID- 24884721
TI  - Simultaneously improving xylose fermentation and tolerance to lignocellulosic
      inhibitors through evolutionary engineering of recombinant Saccharomyces
      cerevisiae harbouring xylose isomerase.
AB  - BACKGROUND: Yeasts tolerant to toxic inhibitors from steam-pretreated
      lignocellulose with xylose co-fermentation capability represent an appealing
      approach for 2nd generation ethanol production. Whereas rational engineering,
      mutagenesis and evolutionary engineering are established techniques for either
      improved xylose utilisation or enhancing yeast tolerance, this report focuses on
      the simultaneous enhancement of these attributes through mutagenesis and
      evolutionary engineering of Saccharomyces cerevisiae harbouring xylose isomerase
      in anoxic chemostat culture using non-detoxified pretreatment liquor from
      triticale straw. RESULTS: Following ethyl methanesulfonate (EMS) mutagenesis,
      Saccharomyces cerevisiae strain D5A+ (ATCC 200062 strain platform), harbouring
      the xylose isomerase (XI) gene for pentose co-fermentation was grown in anoxic
      chemostat culture for 100 generations at a dilution rate of 0.10 h-1 in a medium
      consisting of 60% (v/v) non-detoxified hydrolysate liquor from steam-pretreated
      triticale straw, supplemented with 20 g/L xylose as carbon source. In semi
      aerobic batch cultures in the same medium, the isolated strain D5A(+H) exhibited
      a slightly lower maximum specific growth rate (MU(max) = 0.12 +/- 0.01 h-1) than
      strain TMB3400, with no ethanol production observed by the latter strain. Strain
      D5A(+H) also exhibited a shorter lag phase (4 h vs. 30 h) and complete removal of
      HMF, furfural and acetic acid from the fermentation broth within 24 h, reaching
      an ethanol concentration of 1.54 g/L at a yield (Y(p/s)) of 0.06 g/g xylose and a
      specific productivity of 2.08 g/gh. Evolutionary engineering profoundly affected
      the yeast metabolism, given that parental strain D5A+ exhibited an oxidative
      metabolism on xylose prior to strain development. CONCLUSIONS: Physiological
      adaptations confirm improvements in the resistance to and conversion of
      inhibitors from pretreatment liquor with simultaneous enhancement of xylose to
      ethanol fermentation. These data support the sequential application of random
      mutagenesis followed by continuous culture under simultaneous selective pressure
      from inhibitors and xylose as primary carbon source.

PMID- 24884722
TI  - A Randomized trial of an Asthma Internet Self-management Intervention (RAISIN):
      study protocol for a randomized controlled trial.
AB  - BACKGROUND: The financial costs associated with asthma care continue to increase
      while care remains suboptimal. Promoting optimal self-management, including the
      use of asthma action plans, along with regular health professional review has
      been shown to be an effective strategy and is recommended in asthma guidelines
      internationally. Despite evidence of benefit, guided self-management remains
      underused, however the potential for online resources to promote self-management
      behaviors is gaining increasing recognition. The aim of this paper is to describe
      the protocol for a pilot evaluation of a website 'Living well with asthma' which
      has been developed with the aim of promoting self-management behaviors shown to
      improve outcomes. METHODS/DESIGN: The study is a parallel randomized controlled
      trial, where adults with asthma are randomly assigned to either access to the
      website for 12 weeks, or usual asthma care for 12 weeks (followed by access to
      the website if desired). Individuals are included if they are over 16-years-old,
      have a diagnosis of asthma with an Asthma Control Questionnaire (ACQ) score of
      greater than, or equal to 1, and have access to the internet. Primary outcomes
      for this evaluation include recruitment and retention rates, changes at 12 weeks
      from baseline for both ACQ and Asthma Quality of Life Questionnaire (AQLQ)
      scores, and quantitative data describing website usage (number of times logged
      on, length of time logged on, number of times individual pages looked at, and for
      how long). Secondary outcomes include clinical outcomes (medication use, health
      services use, lung function) and patient reported outcomes (including adherence,
      patient activation measures, and health status). DISCUSSION: Piloting of complex
      interventions is considered best practice and will maximise the potential of any
      future large-scale randomized controlled trial to successfully recruit and be
      able to report on necessary outcomes. Here we will provide results across a range
      of outcomes which will provide estimates of efficacy to inform the design of a
      future full-scale randomized controlled trial of the 'Living well with asthma'
      website. TRIAL REGISTRATION: This trial is registered with Current Controlled
      Trials ISRCTN78556552 on 18/06/13.

PMID- 24884723
TI  - Sulfur K-edge X-ray absorption spectroscopy and density functional theory
      calculations on monooxo Mo(IV) and bisoxo Mo(VI) bis-dithiolenes: insights into
      the mechanism of oxo transfer in sulfite oxidase and its relation to the
      mechanism of DMSO reductase.
AB  - Sulfur K-edge X-ray absorption spectroscopy (XAS) and density functional theory
      (DFT) calculations have been used to determine the electronic structures of two
      complexes [Mo(IV)O(bdt)2](2-) and [Mo(VI)O2(bdt)2](2-) (bdt = benzene-1,2
      dithiolate(2-)) that relate to the reduced and oxidized forms of sulfite oxidase
      (SO). These are compared with those of previously studied dimethyl sulfoxide
      reductase (DMSOr) models. DFT calculations supported by the data are extended to
      evaluate the reaction coordinate for oxo transfer to a phosphite ester substrate.
      Three possible transition states are found with the one at lowest energy,
      stabilized by a P-S interaction, in good agreement with experimental kinetics
      data. Comparison of both oxo transfer reactions shows that in DMSOr, where the
      oxo is transferred from the substrate to the metal ion, the oxo transfer induces
      electron transfer, while in SO, where the oxo transfer is from the metal site to
      the substrate, the electron transfer initiates oxo transfer. This difference in
      reactivity is related to the difference in frontier molecular orbitals (FMO) of
      the metal-oxo and substrate-oxo bonds. Finally, these experimentally related
      calculations are extended to oxo transfer by sulfite oxidase. The presence of
      only one dithiolene at the enzyme active site selectively activates the
      equatorial oxo for transfer, and allows facile structural reorganization during
      turnover. 

PMID- 24884724
TI  - Transcriptome dynamics-based operon prediction in prokaryotes.
AB  - BACKGROUND: Inferring operon maps is crucial to understanding the regulatory
      networks of prokaryotic genomes. Recently, RNA-seq based transcriptome studies
      revealed that in many bacterial species the operon structure vary with the change
      of environmental conditions. Therefore, new computational solutions that use both
      static and dynamic data are necessary to create condition specific operon
      predictions. RESULTS: In this work, we propose a novel classification method that
      integrates RNA-seq based transcriptome profiles with genomic sequence features to
      accurately identify the operons that are expressed under a measured condition.
      The classifiers are trained on a small set of confirmed operons and then used to
      classify the remaining gene pairs of the organism studied. Finally, by linking
      consecutive gene pairs classified as operons, our computational approach produces
      condition-dependent operon maps. We evaluated our approach on various RNA-seq
      expression profiles of the bacteria Haemophilus somni, Porphyromonas gingivalis,
      Escherichia coli and Salmonella enterica. Our results demonstrate that, using
      features depending on both transcriptome dynamics and genome sequence
      characteristics, we can identify operon pairs with high accuracy. Moreover, the
      combination of DNA sequence and expression data results in more accurate
      predictions than each one alone. CONCLUSION: We present a computational strategy
      for the comprehensive analysis of condition-dependent operon maps in prokaryotes.
      Our method can be used to generate condition specific operon maps of many
      bacterial organisms for which high-resolution transcriptome data is available.

PMID- 24884725
TI  - Clear cell variant of follicular thyroid carcinoma with normal thyroid
      stimulating hormone value: a case report.
AB  - INTRODUCTION: Clear cell carcinomas of the thyroid gland with normal thyroid
      stimulating hormone value are very rare, but clear cell changes are described in
      most reported cases of thyroidal lesions. CASE PRESENTATION: In this report, we
      describe the case of a 50-year-old Caucasian woman with a normal thyroid
      stimulating hormone level who underwent surgery to treat a multi-nodular goiter.
      The pathology was a clear cell variant of follicular thyroid carcinoma. The tumor
      was 1cm in diameter and consisted of pure clear cells. CONCLUSION: Clear cell
      variants of follicular thyroid carcinoma are rarely seen, especially it is
      misdiagnosed with metastatic renal cell carcinoma. In this report, we describe
      the case of a patient with a clear cell variant of follicular thyroid carcinoma
      with an interesting pathology.

PMID- 24884726
TI  - Helical tomotherapy with simultaneous integrated boost dose painting for the
      treatment of synchronous primary cancers involving the head and neck.
AB  - OBJECTIVE: To demonstrate the feasibility of helical tomotherapy (HT)-based
      intensity-modulated radiotherapy (IMRT) for the treatment of synchronous primary
      cancers arising from the head and neck. METHODS: 14 consecutive patients with
      histologically proven squamous cell carcinoma of the head and neck were
      determined to have a second primary cancer in the upper aerodigestive tract on
      further evaluation and were treated with HT using simultaneous integrated boost
      IMRT. Megavoltage CT scans were acquired daily as part of an image-guided
      registration protocol. Concurrent platinum-based systemic therapy was given to
      nine patients (64%). RESULTS: HT resulted in durable local control in 21 of the
      28 primary disease sites irradiated, including a complete clinical and
      radiographic response initially observed at 17 of the 20 sites with gross tumour.
      The mean displacements to account for interfraction motion were 2.44 +/- 1.25,
      2.92 +/- 1.09 and 2.31 +/- 1.70 mm for the medial-lateral (ML), superior-inferior
      (SI) and anteroposterior (AP) directions, respectively. Table shifts of >3 mm
      occurred in 19%, 20% and 22% of the ML, SI and AP directions, respectively. The 2
      year estimates of overall survival, local-regional control and progression-free
      survival were 58%, 73% and 60%, respectively. CONCLUSION: The effectiveness of HT
      for the treatment of synchronous primary cancers of the head and neck was
      demonstrated. ADVANCES IN KNOWLEDGE: HT is a feasible option for synchronous
      primary cancers of the head and neck and can result in long-term disease control
      with acceptable toxicity in appropriately selected patients.

PMID- 24884727
TI  - Feasibility of a radiation dose conserving CT protocol for myocardial function
      assessment.
AB  - OBJECTIVE: Assessment of myocardial function can be performed at higher noise
      levels than necessary for coronary arterial evaluation. We evaluated image
      quality and radiation exposure of a dose-conserving function-only acquisition vs
      retrospectively electrocardiogram(ECG)-gated coronary CTA with automatic tube
      current modulation. METHODS: Of 26 patients who underwent clinically indicated
      coronary CTA for coronary and function evaluation, 13 (Group I) underwent
      prospectively ECG-triggered coronary CTA, followed by low-dose retrospectively
      ECG-gated scan for function (128-slice dual-source, 80 kVp; reference tube
      current, 100 mA; 8-mm-thick multiplanar reformatted reconstructions) performed
      either immediately (n = 6) or after 5- to 10-min delay for infarct assessment (n
      = 7). 13 corresponding controls (Group II) underwent retrospectively ECG-gated
      protocols (automatic tube potential selection with CARE kV/CARE Dose 4D; Siemens
      Healthcare, Forchheim, Germany) with aggressive dose modulation. Image quality
      assessment was performed on the six Group I subjects who underwent early post
      contrast dedicated function scan and corresponding controls. Radiation exposure
      was based on dose-length product. RESULTS: Contrast-to-noise ratio (CNR) was
      preserved throughout the cardiac cycle in Group I and varied according to dose
      modulation in Group II. Visual image quality indices were similar during end
      systole but were better in Group II at end diastole. Although the total radiation
      exposure was equivalent in Group I and Group II (284 vs 280 mGy cm), the median
      radiation exposure associated with only the dedicated function scan was 138 mGy
      cm (interquartile range, 116-203 mGy cm). CONCLUSION: A low-dose retrospective
      ECG-gated protocol permits assessment of myocardial function at a median
      radiation exposure of 138 mGy cm and offers more consistent multiphase CNR vs
      traditional ECG-modulation protocols. This is useful for pure functional
      evaluation or as an adjunct to single-phase scan modes. ADVANCES IN KNOWLEDGE:
      Radiation exposure can be limited with a tailored myocardial function CT protocol
      while maintaining preserved images.

PMID- 24884728
TI  - The average receiver operating characteristic curve in multireader multicase
      imaging studies.
AB  - OBJECTIVE: In multireader, multicase (MRMC) receiver operating characteristic
      (ROC) studies for evaluating medical imaging systems, the area under the ROC
      curve (AUC) is often used as a summary metric. Owing to the limitations of AUC,
      plotting the average ROC curve to accompany the rigorous statistical inference on
      AUC is recommended. The objective of this article is to investigate methods for
      generating the average ROC curve from ROC curves of individual readers. METHODS:
      We present both a non-parametric method and a parametric method for averaging ROC
      curves that produce a ROC curve, the area under which is equal to the average AUC
      of individual readers (a property we call area preserving). We use hypothetical
      examples, simulated data and a real-world imaging data set to illustrate these
      methods and their properties. RESULTS: We show that our proposed methods are area
      preserving. We also show that the method of averaging the ROC parameters, either
      the conventional bi-normal parameters (a, b) or the proper bi-normal parameters
      (c, da), is generally not area preserving and may produce a ROC curve that is
      intuitively not an average of multiple curves. CONCLUSION: Our proposed methods
      are useful for making plots of average ROC curves in MRMC studies as a companion
      to the rigorous statistical inference on the AUC end point. The software
      implementing these methods is freely available from the authors. ADVANCES IN
      KNOWLEDGE: METHODS for generating the average ROC curve in MRMC ROC studies are
      formally investigated. The area-preserving criterion we defined is useful to
      evaluate such methods.

PMID- 24884729
TI  - A polymorphism in the DNA repair domain of APEX1 is associated with the radiation
      induced pneumonitis risk among lung cancer patients after radiotherapy.
AB  - OBJECTIVE: To examine the association of tag single nucleotide polymorphisms
      (tagSNPs) (rs1130409, rs1760944, rs2307486 and rs3136817) in APEX1 with the risk
      of severe radiation-induced pneumonitis (RP) after radiotherapy among Han Chinese
      patients with lung cancer. METHODS: A total of 168 patients with lung cancer who
      were receiving radiotherapy were prospectively recruited. RP was evaluated
      according to the Radiation Therapy Oncology Group. A case-control study was
      performed. The case group included patients with RP grade of >=3, while the
      control group comprised patients with RP grades <3. Four tagSNPs of APEX1 were
      genotyped in 126 patients with complete follow-up by multi-SNaPshot(r) (Genesky
      Biotechnologies Inc., Shanghai, China) genotyping assays. RESULTS were assessed
      by a logistic regression model for RP risk and Mantal-Cox log-rank test for the
      cumulative RP probability by the genotypes. RESULTS: rs1130409 was associated
      with severe RP. GT genotype of rs1130409 was significantly higher in patients
      with RP than in those of the control group [68.8% vs 41.8%; p = 0.025; resulting
      odds ratio (OR), 5.98]. Patients with lung cancer bearing the G allele had a 5.83
      fold higher risk of RP than those with the wild TT genotype [OR = 5.83; 95%
      confidence interval (CI), 1.27-26.90; p = 0.024], and this was further confirmed
      by the binary regression adjusted by some confounding factors, including
      Karnofsky performance scale, concurrent chemotherapy-radiotherapy and lung volume
      receiving >30 Gy (OR = 6.96; 95% CI, 1.36-35.77; p = 0.02). rs1130409 was also
      associated with the time to occurrence of severe RP (p = 0.04). Three-dimensional
      model APEX1 protein showed that rs1130409 is located in the random coil structure
      corresponding to the DNA repair function region. ADVANCES IN KNOWLEDGE: rs1130409
      of APEX1 can be a predictor of RP grades >=3 among patients with lung cancer.

PMID- 24884730
TI  - Cancer incidence in Ghana, 2012: evidence from a population-based cancer
      registry.
AB  - BACKGROUND: Data on cancers is a challenge in most developing countries.
      Population-based cancer registries are also not common in developing countries
      despite the usefulness of such registries in informing cancer prevention and
      control programmes. The availability of population-based data on cancers in
      Africa varies across different countries. In Ghana, data and research on cancer
      have focussed on specific cancers and have been hospital-based with no reference
      population. The Kumasi Cancer Registry was established as the first population
      based cancer registry in Ghana in 2012 to provide information on cancer cases
      seen in the city of Kumasi. METHODS: This paper reviews data from the Kumasi
      Cancer Registry for the year 2012. The reference geographic area for the registry
      is the city of Kumasi as designated by the 2010 Ghana Population and Housing
      Census. Data was from all clinical departments of the Komfo Anokye Teaching
      Hospital, Pathology Laboratory Results, Death Certificates and the Kumasi South
      Regional Hospital. Data was abstracted and entered into Canreg 5 database.
      Analysis was conducted using Canreg 5, Microsoft Excel and Epi Info Version
      7.1.2.0. RESULTS: The majority of cancers were recorded among females accounting
      for 69.6% of all cases. The mean age at diagnosis for all cases was 51.6 years.
      Among males, the mean age at diagnosis was 48.4 compared with 53.0 years for
      females. The commonest cancers among males were cancers of the Liver (21.1%),
      Prostate (13.2%), Lung (5.3%) and Stomach (5.3%). Among females, the commonest
      cancers were cancers of the Breast (33.9%), Cervix (29.4%), Ovary (11.3%) and
      Endometrium (4.5%). Histology of the primary tumour was the basis of diagnosis in
      74% of cases with clinical and other investigations accounting for 17% and 9%
      respectively. The estimated cancer incidence Age Adjusted Standardised Rate for
      males was 10.9/100,000 and 22.4/100, 000 for females. CONCLUSION: This first
      attempt at population-based cancer registration in Ghana indicates that such
      registries are feasible in resource limited settings as ours. Strengthening
      Public Health Surveillance and establishing more Population-based Cancer
      Registries will help improve data quality and national efforts at cancer
      prevention and control in Ghana.

PMID- 24884731
TI  - The effect of mannitol on intraoperative brain relaxation in patients undergoing
      supratentorial tumor surgery: study protocol for a randomized controlled trial.
AB  - BACKGROUND: The risk of brain swelling after dural opening is high in patients
      with midline shift undergoing supratentorial tumor surgery. Brain swelling may
      result in increased intracranial pressure, impeded tumor exposure, and adverse
      outcomes. Mannitol is recommended as a first-line dehydration treatment to reduce
      brain edema and enable brain relaxation during neurosurgery. Research has
      indicated that mannitol enhanced brain relaxation in patients undergoing
      supratentorial tumor surgery; however, these results need further confirmation,
      and the optimal mannitol dose has not yet been established. We propose to examine
      whether different doses of 20% mannitol improve brain relaxation in a dose
      dependent manner when administered at the time of incision. We will examine
      patients with preexisting mass effects and midline shift undergoing elective
      supratentorial brain tumor surgery. METHODS: This is a single-center, randomized
      controlled, parallel group trial that will be carried out at Beijing Tiantan
      Hospital, Capital Medical University. Randomization will be achieved using a
      computer-generated table. The study will include 220 patients undergoing
      supratentorial tumor surgery whose preoperative computed tomography/magnetic
      resonance imaging results indicate a brain midline shift. Patients in group A,
      group B, and group C will receive dehydration treatment at incision with 20%
      mannitol solutions of 0.7, 1.0, and 1.4 g/kg, respectively, at a rate of 600
      mL/h. The patients in the control group will not receive mannitol. The primary
      outcome is an improvement in intraoperative brain relaxation and dura tension
      after dehydration with mannitol. Secondary outcomes are postoperative outcomes
      and the incidence of mannitol side effects. DISCUSSION: The aim of this study is
      to determine the optimal dose of 20% mannitol for intraoperative infusion. We
      will examine brain relaxation and outcome in patients undergoing supratentorial
      tumor surgery. If our results are positive, the study will indicate the optimal
      dose of mannitol to improve brain relaxation and avoid side effects during brain
      tumor surgery. TRIAL REGISTRATION: The study is registered with the registry
      website http://www.chictr.org with the registration number ChiCTRTRC13003984 (17
      December 2013).

PMID- 24884732
TI  - microRNA-182 targets special AT-rich sequence-binding protein 2 to promote
      colorectal cancer proliferation and metastasis.
AB  - BACKGROUND: Increasing evidence has revealed that microRNAs (miRNA) played a
      pivotal role in regulating cancer cell proliferation and metastasis. The
      deregulation of miR-182 has been identified in colorectal cancer (CRC). However,
      the role and mechanism of miR-182 in CRC have not been completely understood yet.
      METHODS: The expression levels of miR-182 in CRC tissues and CRC cell lines were
      examined by performing stem-loop quantitative RT-PCR. The stable over-expression
      miR-182 cell lines and control cell lines were constructed by lentivirus
      infection. Subsequently, CCK-8 assay, plate colony formation assay, cell
      migration, invasion assay and experimental animal models were performed to detect
      the biological functions of miR-182 in vitro and in vivo. A luciferase reporter
      assay was conducted to confirm target associations. Western blot and
      immunohistochemical analysis were performed to examine the expression changes of
      molecular markers that are regulated by miR-182. RESULTS: We found that miR-182
      expression is increased in CRC cells that originated from metastatic foci and
      human primary CRC tissues with lymph node metastases. The ectopic expression of
      miR-182 enhanced cell proliferation, invasion, and migration in vitro. Stable
      overexpression of miR-182 also facilitated tumor growth and metastasis in vivo
      too. Further research showed that miR-182 could directly target the
      3'untranslated region (3'UTR) of SATB2 mRNA and subsequently repress both the
      mRNA and protein expressions of SATB2, which we identified in previous studies as
      a CRC metastasis-associated protein. Restoring SATB2 expression could reverse the
      effects of miR-182 on CRC cell proliferation and migration. Investigations of
      possible mechanisms underlying these behaviors induced by miR-182 revealed that
      miR-182 induced epithelial-mesenchymal transition (EMT) by modulating the
      expression of key cellular molecules in EMT. CONCLUSIONS: Our results illustrated
      that the up-regulation of miR-182 played a pivotal role in CRC tumorigenesis and
      metastasis, which suggesting a potential implication of miR-182 in the molecular
      therapy for CRC.

PMID- 24884734
TI  - Sexual behavior and knowledge of human immunodeficiency virus/aids and sexually
      transmitted infections among women inmates of Briman Prison, Jeddah, Saudi
      Arabia.
AB  - BACKGROUND: To reduce the incidence of HIV and sexually transmitted infections
      (STIs), it is necessary to target high-risk populations such as prison inmates.
      This study aims to explore the range of knowledge on HIV and STIs, sexual
      behaviors, and adoption of preventive measures among women inmates. METHODS: This
      was a survey conducted between July 1, 2012 and July 29, 2012 among women inmates
      at Briman Prison, Jeddah, Saudi Arabia. The author gave an educational lecture on
      STIs in a conference room at the prison. Educational material was distributed to
      the attendees after the lecture, and the survey was conducted one week later. All
      the participants were asked to complete an anonymous 40-item self-administered
      questionnaire in the presence of a professional health assistant and a
      translator, for non-Arabic speakers. Data collected included the personal data of
      the respondent, her alleged criminal background, penal status, accumulative time
      in prison, history of smoking, alcohol or drug addiction, knowledge about the
      seven most common STIs, symptoms, modes of transmission, prevention, sexual
      activity, addiction, and means of protection. Descriptive analysis was performed
      using Microsoft Excel. RESULTS: We interviewed 204 women aged 16-60 years (mean,
      33.3 years). Most of the respondents (n = 170; 83 . 0%) were not aware of STIs;
      117 respondents (57 . 4%) did not undergo screening for STIs before marriage or
      intercourse, while only 59 (28 . 9%) did. Over half of the respondents (n = 107;
      52.5%) thought they knew how to protect themselves from STIs. Nevertheless, 87
      (42.6%) were uncertain about the role of condoms in protection from STIs and (n =
      41; 20.1%) thought condoms provide 100% protection against STIs, while 72
      respondents (35.3%) thought condoms did not confer 100% protection against STIs.
      Only 10 respondents (4.9%) used condoms to protect themselves from STIs. Saudi
      women (P = 0.033) and those with a higher level of education (P < 0.01) were
      significantly more likely to have better knowledge. CONCLUSION: Women inmates at
      Briman Prison have poor knowledge of STIs as well as risky sexual behaviors.
      Campaigns aimed at increasing awareness of STIs should also target prison
      inmates, who in general constitute high-risk populations.

PMID- 24884733
TI  - USP18 is crucial for IFN-gamma-mediated inhibition of B16 melanoma tumorigenesis
      and antitumor immunity.
AB  - BACKGROUND: Interferon (IFN)-gamma-mediated immune response plays an important
      role in tumor immunosurveillance. However, the regulation of IFN-gamma-mediated
      tumorigenesis and immune response remains elusive. USP18, an interferon
      stimulating response element, regulates IFN-alpha-mediated signaling in anti
      viral immune response, but its role in IFN-gamma-mediated tumorigenesis and anti
      tumor immune response is unknown. METHOD: In this study, USP18 in tumorigenesis
      and anti-tumor immune response was comprehensively appraised in vivo by
      overexpression or downregulation its expression in murine B16 melanoma tumor
      model in immunocompetent and immunodeficient mice. RESULTS: Ectopic expression or
      downregulation of USP18 in B16 melanoma tumor cells inhibited or promoted
      tumorigenesis, respectively, in immunocompetent mice. USP18 expression in B16
      melanoma tumor cells regulated IFN-gamma-mediated immunoediting, including
      upregulating MHC class-I expression, reducing tumor cell-mediated inhibition of T
      cell proliferation and activation, and suppressing PD-1 expression in CD4+ and
      CD8+ T cells in tumor-bearing mice. USP18 expression in B16 melanoma tumor cells
      also enhanced CTL activity during adoptive immunotherapy by prolonging the
      persistence and enhancing the activity of adoptively transferred CTLs and by
      reducing CTL exhaustion in the tumor microenvironment. Mechanistic studies
      demonstrated that USP18 suppressed tumor cell-mediated immune inhibition by
      activating T cells, inhibiting T-cell exhaustion, and reducing dendritic cell
      tolerance, thus sensitizing tumor cells to immunosurveillance and immunotherapy.
      CONCLUSION: These findings suggest that stimulating USP18 is a feasible approach
      to induce B16 melanoma specific immune response.

PMID- 24884735
TI  - The role of childhood social position in adult type 2 diabetes: evidence from the
      English Longitudinal Study of Ageing.
AB  - BACKGROUND: Socioeconomic circumstances in childhood and early adulthood may
      influence the later onset of chronic disease, although such research is limited
      for type 2 diabetes and its risk factors at the different stages of life. The
      main aim of the present study is to examine the role of childhood social position
      and later inflammatory markers and health behaviours in developing type 2
      diabetes at older ages using a pathway analytic approach. METHODS: Data on
      childhood and adult life circumstances of 2,994 men and 4,021 women from English
      Longitudinal Study of Ageing (ELSA) were used to evaluate their association with
      diabetes at age 50 years and more. The cases of diabetes were based on having
      increased blood levels of glycated haemoglobin and/or self-reported medication
      for diabetes and/or being diagnosed with type 2 diabetes. Father's job when ELSA
      participants were aged 14 years was used as the measure of childhood social
      position. Current social characteristics, health behaviours and inflammatory
      biomarkers were used as potential mediators in the statistical analysis to assess
      direct and indirect effects of childhood circumstances on diabetes in later life.
      RESULTS: 12.6 per cent of participants were classified as having diabetes. A
      disadvantaged social position in childhood, as measured by father's manual
      occupation, was associated at conventional levels of statistical significance
      with an increased risk of type 2 diabetes in adulthood, both directly and
      indirectly through inflammation, adulthood social position and a risk score
      constructed from adult health behaviours including tobacco smoking and limited
      physical activity. The direct effect of childhood social position was reduced by
      mediation analysis (standardised coefficient decreased from 0.089 to 0.043) but
      remained statistically significant (p= 0.035). All three indirect pathways made a
      statistically significantly contribution to the overall effect of childhood
      social position on adulthood type 2 diabetes. CONCLUSIONS: Childhood social
      position influences adult diabetes directly and indirectly through inflammatory
      markers, adulthood social position and adult health behaviours.

PMID- 24884736
TI  - Complementary and alternative therapies for treatment of insomnia in women in
      postmenopause.
AB  - Menopause is an important episode in the life of women and, for the great
      majority of women, occurs in their fifties. The climacteric period, which is
      often associated with insomnia, represents one of the most important changes in
      the female reproductive cycle because it marks the end of reproductive capacity.
      Hormonal therapy has been considered the most useful and standardized method for
      treating menopause and climacteric-associated symptoms despite its side-effects.
      The present study is a review of the scientific literature about the efficacy,
      toxicity and safety of complementary and alternative therapies used as
      alternatives to hormone therapy to treat insomnia in menopausal women. Mind-body
      therapies and the use of isoflavonoids have exhibited promise as interventions
      for treating insomnia in the climacteric at our Walk-In Clinic of Sleep
      Disturbance at the Universidade Federal de Sao Paulo. This review will describe
      the use of complementary and alternative therapies and their effectiveness in
      treating insomnia in this period of a woman's life.

PMID- 24884737
TI  - Common genetic variation of the APOE gene and personality.
AB  - BACKGROUND: A recent study yielded first evidence that personality plays an
      important role in explaining the influence of a prominent APOE polymorphism on
      cognitive decline and Alzheimer's disease (AD) in elderly humans. Adding to this,
      two earlier studies examined this polymorphism in the context of individual
      differences in temperament traits in young humans with mixed results. In general,
      research linking the prominent APOE epsilon2, epsilon3 and epsilon4 variants and
      human personality is of special interest, because an influence of this gene and
      its prominent polymorphism on personality in young adulthood could be of
      diagnostic value to predict AD and its development in later years. RESULTS: In
      the present study N = 531 participants provided buccal swabs and filled in a self
      report inventory measuring the Five Factor Model of Personality. No association
      between common genetic variations of the APOE gene (in detail the genotypes
      epsilon3/epsilon3, epsilon2/epsilon3 and epsilon3/epsilon4) and personality could
      be observed. The remaining genotypes, including the high risk constellation
      epsilon4/epsilon4 for AD, were too seldom to be tested. CONCLUSIONS: In sum, the
      present study yielded no evidence for a direct link between common genetic
      variants of the APOE gene and personality in young adulthood.

PMID- 24884739
TI  - Can an e-learning course improve nursing care for older people at risk of
      delirium: a stepped wedge cluster randomised trial.
AB  - BACKGROUND: Delirium occurs frequently in older hospitalised patients and is
      associated with several adverse outcomes. Ignorance among healthcare
      professionals and a failure to recognise patients suffering from delirium have
      been identified as the possible causes of poor care. The objective of the study
      was to determine whether e-learning can be an effective means of improving
      implementation of a quality improvement project in delirium care. This project
      aims primarily at improving the early recognition of older patients who are at
      risk of delirium. METHODS: In a stepped wedge cluster randomised trial an e
      learning course on delirium was introduced, aimed at nursing staff. The trial was
      conducted on general medical and surgical wards from 18 Dutch hospitals. The
      primary outcome measure was the delirium risk screening conducted by nursing
      staff, measured through monthly patient record reviews. Patient records from
      patients aged 70 and over admitted onto wards participating in the study were
      used for data collection. Data was also collected on the level of delirium
      knowledge of these wards' nursing staff. RESULTS: Records from 1,862 older
      patients were included during the control phase and from 1,411 patients during
      the intervention phase. The e-learning course on delirium had a significant
      positive effect on the risk screening of older patients by nursing staff (OR 1.8,
      p-value <0.01), as well as on other aspects of delirium care. The number of
      patients diagnosed with delirium was reduced from 11.2% in the control phase to
      8.7% in the intervention phase (p = 0.04). The e-learning course also showed a
      significant positive effect on nurses' knowledge of delirium. CONCLUSIONS: Nurses
      who undertook a delirium e-learning course showed a greater adherence to the
      quality improvement project in delirium care. This improved the recognition of
      patients at risk and demonstrated that e-learning can be a valuable instrument
      for hospitals when implementing improvements in delirium care. TRIAL
      REGISTRATION: The Netherlands National Trial Register (NTR). TRIAL NUMBER:
      NTR2885.

PMID- 24884738
TI  - Pulmonary symptoms and diagnoses are associated with HIV in the MACS and WIHS
      cohorts.
AB  - BACKGROUND: Several lung diseases are increasingly recognized as comorbidities
      with HIV; however, few data exist related to the spectrum of respiratory
      symptoms, diagnostic testing, and diagnoses in the current HIV era. The objective
      of the study is to determine the impact of HIV on prevalence and incidence of
      respiratory disease in the current era of effective antiretroviral treatment.
      METHODS: A pulmonary-specific questionnaire was administered yearly for three
      years to participants in the Multicenter AIDS Cohort Study (MACS) and Women's
      Interagency HIV Study (WIHS). Adjusted prevalence ratios for respiratory
      symptoms, testing, or diagnoses and adjusted incidence rate ratios for diagnoses
      in HIV-infected compared to HIV-uninfected participants were determined. Risk
      factors for outcomes in HIV-infected individuals were modeled. RESULTS: Baseline
      pulmonary questionnaires were completed by 907 HIV-infected and 989 HIV
      uninfected participants in the MACS cohort and by 1405 HIV-infected and 571 HIV
      uninfected participants in the WIHS cohort. In MACS, dyspnea, cough, wheezing,
      sleep apnea, and incident chronic obstructive pulmonary disease (COPD) were more
      common in HIV-infected participants. In WIHS, wheezing and sleep apnea were more
      common in HIV-infected participants. Smoking (MACS and WIHS) and greater body
      mass index (WIHS) were associated with more respiratory symptoms and diagnoses.
      While sputum studies, bronchoscopies, and chest computed tomography scans were
      more likely to be performed in HIV-infected participants, pulmonary function
      tests were no more common in HIV-infected individuals. Respiratory symptoms in
      HIV-infected individuals were associated with history of pneumonia,
      cardiovascular disease, or use of HAART. A diagnosis of asthma or COPD was
      associated with previous pneumonia. CONCLUSIONS: In these two cohorts, HIV is an
      independent risk factor for several respiratory symptoms and pulmonary diseases
      including COPD and sleep apnea. Despite a higher prevalence of chronic
      respiratory symptoms, testing for non-infectious respiratory diseases may be
      underutilized in the HIV-infected population.

PMID- 24884740
TI  - Stability and change in alcohol habits of different socio-demographic subgroups-
      a cohort study.
AB  - BACKGROUND: Stability in alcohol habits varies over time and in subgroups, but
      there are few longitudinal studies assessing stability in alcohol habits by socio
      demographic subgroups and potential predictors of stability and change. The aim
      was to study stability and change in alcohol habits by sex, age, and socio
      economic position (SEP). METHODS: Data derived from two longitudinal population
      based studies in Sweden; the PART study comprising 19 457 individuals aged 20-64
      years in 1998-2000, and the Stockholm Public Health Cohort (SPHC) with 50 067
      individuals aged 18-84 years in 2002. Both cohorts were followed-up twice; PART
      2000-2003 and 2010, and SPHC 2007 and 2010. Alcohol habits were measured with the
      Alcohol Use Disorders Identification Test (AUDIT), and with normal weekly alcohol
      consumption (NWAC). Stability in alcohol habits was measured with intraclass
      correlation. Odds ratios were estimated in multinomial logistic regression
      analysis to predict stability in alcohol habits. RESULTS: For the two drinking
      measures there were no consistent patterns of stability in alcohol habits by sex
      or educational level. The stability was higher for older age groups and self
      employed women. To be a man aged 30-39 at baseline predicted both increase and
      decrease in alcohol habits. CONCLUSIONS: The findings illustrate higher stability
      in alcohol habits with increasing age and among self-employed women with risky
      alcohol habits. To be a man and the age 30-39 predicted change in alcohol habits.
      No conclusive pattern of socio-economic position as predictor of change in
      alcohol habits was found and other studies of potential predictors seem
      warranted.

PMID- 24884741
TI  - Tickling the TLR7 to cure viral hepatitis.
AB  - Chronic hepatitis B and C are the leading causes of liver disease and liver
      transplantation worldwide. Ability to mount an effective immune response against
      both HBV and HCV is associated with spontaneous clearance of both infections,
      while an inability to do so leads to chronicity of both infections. To mount an
      effective immune response, both innate and adaptive immune responses must work in
      tandem. Hence, developing protective immunity to hepatitis viruses is an
      important goal in order to reduce the global burden of these two infections and
      prevent development of long-term complications. In this regard, the initial
      interactions between the pathogen and immune system are pivotal in determining
      the effectiveness of immune response and subsequent elimination of pathogens.
      Toll-like receptors (TLRs) are important regulators of innate and adaptive immune
      responses to various pathogens and are often involved in initiating and
      augmenting effective antiviral immunity. Immune-based therapeutic strategies that
      specifically induce type I interferon responses are associated with functional
      cure for both chronic HBV and HCV infections. Precisely, TLR7 stimulation
      mediates an endogenous type I interferon response, which is critical in
      development of a broad, effective and protective immunity against hepatitis
      viruses. This review focuses on anti-viral strategies that involve targeting TLR7
      that may lead to development of protective immunity and eradication of hepatitis
      B. 

PMID- 24884742
TI  - Socioeconomic inequalities and body mass index in Vasterbotten County, Sweden: a
      longitudinal study of life course influences over two decades.
AB  - INTRODUCTION: Life course socioeconomic inequalities in heart disease, stroke and
      all-cause mortality are well studied in Sweden. However, few studies have sought
      to explain the mechanism for such associations mainly due to lack of longitudinal
      data with multiple measures of socioeconomic status (SES) across the life course.
      Given the population health concern about how socioeconomic inequality is related
      to poorer health, we aim to tackle obesity as one of the prime suspects that
      could explain the association between SES inequality and cardiovascular disease
      and consequently premature death. The aim of this study is to test which life
      course model best describes the association between socioeconomic disadvantage
      and obesity among 60 year old inhabitants of Vasterbotten County in Northern
      Sweden. METHODS: A birth cohort consisting of 3340 individuals born between 1930
      and 1932 was studied. Body mass index (BMI) at the age of 60 and information on
      socioeconomic status at three stages of life (ages 40, 50, and 60 years) was
      collected. Independent samples t-test was used to compare BMI between advantaged
      and disadvantaged groups and one-way ANOVA was used to compare BMI among eight
      SES trajectories. We applied a structured modeling approach to examine three
      different hypothesized life course SES models (accumulation, critical period, and
      social mobility) in relation to BMI. RESULTS: We found sex differences in the way
      that late adulthood socioeconomic disadvantage is associated with BMI among
      inhabitants of Northern Sweden. Our study suggests that social adversity in all
      stages of late adulthood is a particularly important indicator for addressing the
      social gradients in BMI among women in Northern Sweden and that unhealthy
      behaviors in terms of smoking and physical inactivity are insufficient to explain
      the relationships between social and lifestyle inequalities and BMI. CONCLUSION:
      In order for local authorities to develop informed preventive efforts, we suggest
      further research to identify modifiable risk factors across the life course which
      could explain this health inequality.

PMID- 24884743
TI  - Sigmoid colon cancer arising in a diverticulum of the colon with involvement of
      the urinary bladder: a case report and review of the literature.
AB  - BACKGROUND: Colon cancer can arise from the mucosa in a colonic diverticulum.
      Although colon diverticulum is a common disease, few cases have been previously
      reported on colon cancer associated with a diverticulum. We report a rare case of
      sigmoid colon cancer arising in a diverticulum with involvement of the urinary
      bladder, which presented characteristic radiographic images. CASE PRESENTATION: A
      73-year-old man was admitted to our hospital for macroscopic hematuria. Computed
      tomography and magnetic resonance imaging revealed a sigmoid colon tumor that
      protruded into the urinary bladder lumen. The radiographs showed a tumor with a
      characteristic dumbbell-shaped appearance. Colonoscopy showed a type 1 cancer and
      multiple diverticula in the sigmoid colon. A diagnosis of sigmoid colon cancer
      with involvement of the urinary bladder was made based on the pathological
      findings of the biopsied specimens. We performed sigmoidectomy and total
      resection of the urinary bladder with colostomy and urinary tract diversion.
      Histopathological findings showed the presence of a colovesical fistula due to
      extramurally growing colon cancer. Around the colon cancer, the normal colon
      mucosa was depressed sharply with lack of the muscular layer, suggesting that the
      colon cancer was arising from a colon diverticulum. CONCLUSION: The present case
      is the first report of sigmoid colon cancer arising in a diverticulum with
      involvement of the urinary bladder. Due to an accurate preoperative radiological
      diagnosis, we were able to successfully perform a curative resection for sigmoid
      colon cancer arising in a diverticulum with involvement of the urinary bladder.

PMID- 24884744
TI  - Accuracy of portrayal by standardized patients: results from four OSCE stations
      conducted for high stakes examinations.
AB  - BACKGROUND: The reliability in Objective Structured Clinical Exams (OSCEs) is
      based on variance introduced due to examiners, stations, items, standardized
      patients (SP), and the interaction of one or more of these items with the
      candidates. The impact of SPs on the reliability has not been well studied.
      Accordingly, the main purpose of the present study was to assess the accuracy of
      portrayal by standardized patients. METHODS: Four stations from a ten station
      high-stakes OSCE were selected for video recording. Due to the large number of
      candidates to be evaluated, the OSCE was administered using four assessment
      tracks. Four SPs were trained for each case (n = 16). Two physician assessors
      were trained to assess the accuracy of SP portrayal using a station-specific
      instrument based on the station guidelines. For the items with disagreement a
      third physician was asked to review and the mode was used for analysis. Each
      instrument included case-specific items on verbal and physical portrayal using a
      3-point rating scale ("yes", "yes, but" and "not done"). The physician assessors
      also scored each SP on their overall performance based on a 5-item anchored
      global rating scale ("very poor", "poor", "ok", "good", and "very good"). SPs at
      location 1 were trained by one trainer and SPs at location 2 had another trainer.
      All SPs were employed in a high-stakes OSCE for at least the second time.
      RESULTS: The reliability of rating scores ranged from Cronbach's alpha of .40 to
      .74. Verbal portrayal by SPs did not significantly differ for most items;
      however, the facial expressions of the SPs differed significantly (p < .05). An
      emergency management station that depended heavily on SPs physical presentation
      and facial expressions differed between all four SPs trained for that station.
      CONCLUSIONS: Variation of trained SP portrayal of the same station across
      different tracks and at different times in OSCE may contribute substantial error
      to OSCE assessments. The training of SPs should be strengthened and constantly
      monitored during the exam to ensure that the examinees' scores are a true
      reflection of their competency and devoid of exam errors.

PMID- 24884745
TI  - Evolution of sperm morphology in anurans: insights into the roles of mating
      system and spawning location.
AB  - BACKGROUND: The degree of postcopulatory sexual selection, comprising variable
      degrees of sperm competition and cryptic female choice, is an important
      evolutionary force to influence sperm form and function. Here we investigated the
      effects of mating system and spawning location on the evolution of sperm
      morphology in 67 species of Chinese anurans. We also examined how relative testes
      size as an indicator of the level of sperm competition affected variation in
      sperm morphology across a subset of 29 species. RESULTS: We found a significant
      association of mating system and spawning location with sperm morphology.
      However, when removing the effects of body mass or absolute testes mass for
      species for which such data were available, this effect became non-significant.
      Consistent with predictions from sperm competition theory, we found a positive
      correlation between sperm morphology and relative testes size after taking
      phylogeny into account. CONCLUSIONS: Our findings suggest that sexual selection
      in Chinese anurans favors longer sperm when the level of sperm competition is
      high. Pre-copulatory male-male competition and spawning location, on the other
      hand, do not affect the evolution of sperm morphology after taking body mass and
      absolute testes mass into account.

PMID- 24884746
TI  - Latent phenotypes pervade gene regulatory circuits.
AB  - BACKGROUND: Latent phenotypes are non-adaptive byproducts of adaptive phenotypes.
      They exist in biological systems as different as promiscuous enzymes and genome
      scale metabolic reaction networks, and can give rise to evolutionary adaptations
      and innovations. We know little about their prevalence in the gene expression
      phenotypes of regulatory circuits, important sources of evolutionary innovations.
      RESULTS: Here, we study a space of more than sixteen million three-gene model
      regulatory circuits, where each circuit is represented by a genotype, and has one
      or more functions embodied in one or more gene expression phenotypes. We find
      that the majority of circuits with single functions have latent expression
      phenotypes. Moreover, the set of circuits with a given spectrum of functions has
      a repertoire of latent phenotypes that is much larger than that of any one
      circuit. Most of this latent repertoire can be easily accessed through a series
      of small genetic changes that preserve a circuit's main functions. Both circuits
      and gene expression phenotypes that are robust to genetic change are associated
      with a greater number of latent phenotypes. CONCLUSIONS: Our observations suggest
      that latent phenotypes are pervasive in regulatory circuits, and may thus be an
      important source of evolutionary adaptations and innovations involving gene
      regulation.

PMID- 24884747
TI  - Health-related quality of life is not impaired in children with undetected as
      well as diagnosed celiac disease: a large population based cross-sectional study.
AB  - BACKGROUND: Knowledge regarding the health-related quality of life (HRQoL) of
      children with celiac disease remains limited and inconclusive. We investigated
      the HRQoL of three groups of 12-year-olds with: i) undetected celiac disease ii)
      clinically diagnosed celiac disease, and iii) without celiac disease. METHODS: A
      school-based cross-sectional multicenter screening study invited 18 325 children,
      whereof 68% consented to participate. Participants provided a blood sample, which
      was later analyzed for anti-tissue-tranglutaminase antibodies, and alongside
      filled in a questionnaire. When anti-tissue-tranglutaminase antibodies were
      elevated, a small intestinal biopsy verified the screening-detected celiac
      disease diagnosis. Self-reported HRQoL was measured using Kidscreen, a generic 52
      items instrument with proven reliability and validity. Scores were linearly
      transformed into a 0-100 scale with higher values indicating better HRQoL. Mean
      values with standard deviations (mean +/- SD) were compared, and uni- and
      multivariate logistic regression models tested the odds of a low HRQoL among
      children with undetected or diagnosed celiac disease, respectively. RESULTS:
      Children with undetected celiac disease (n = 238) reported similar HRQoL as
      children without celiac disease (n = 12 037) (83.0 +/- 11.0 vs. 82.5 +/- 11.3, P
      = 0.51), and also similar HRQoL (82.2 +/- 12.2, P = 0.28) to that of children
      with diagnosed celiac disease (n = 90), of whom 92% were adherent to treatment.
      Having undetected celiac disease did not increase the odds of low overall HRQoL,
      independent of sex, area of residence, study year and occurrence of
      gastrointestinal symptoms (adjusted odds ratio 0.77, 95% CI 0.54-1.10).
      Comparable results were seen for diagnosed celiac disease cases (adjusted odds
      ratio 1.11, 95% CI 0.67-1.85). CONCLUSION: Children with undetected celiac
      disease reported comparable HRQoL as their peers with diagnosed celiac disease,
      and those without celiac disease, when reporting prior to receiving the diagnosis
      through screening. Thus, children with celiac disease, both untreated and
      diagnosed, perceive their HRQoL as unimpaired by their disease.

PMID- 24884749
TI  - The economics of resistant pathogens and antibiotic innovation.

PMID- 24884748
TI  - Cadmium exposure and sulfate limitation reveal differences in the transcriptional
      control of three sulfate transporter (Sultr1;2) genes in Brassica juncea.
AB  - BACKGROUND: Cadmium (Cd) exposure and sulfate limitation induce root sulfate
      uptake to meet the metabolic demand for reduced sulfur. Although these responses
      are well studied, some aspects are still an object of debate, since little is
      known about the molecular mechanisms by which changes in sulfate availability and
      sulfur metabolic demand are perceived and transduced into changes in the
      expression of the high-affinity sulfate transporters of the roots. The analysis
      of the natural variation occurring in species with complex and highly redundant
      genome could provide precious information to better understand the topic, because
      of the possible retention of mutations in the sulfate transporter genes. RESULTS:
      The analysis of plant sulfur nutritional status and root sulfate uptake performed
      on plants of Brassica juncea - a naturally occurring allotetraploid species -
      grown either under Cd exposure or sulfate limitation showed that both these
      conditions increased root sulfate uptake capacity but they caused quite
      dissimilar nutritional states, as indicated by changes in the levels of
      nonprotein thiols, glutathione and sulfate of both roots and shoots. Such
      behaviors were related to the general accumulation of the transcripts of the
      transporters involved in root sulfate uptake (BjSultr1;1 and BjSultr1;2).
      However, a deeper analysis of the expression patterns of three redundant, fully
      functional, and simultaneously expressed Sultr1;2 forms (BjSultr1;2a,
      BjSultr1;2b, BjSultr1;2c) revealed that sulfate limitation induced the expression
      of all the variants, whilst BjSultr1;2b and BjSultr1;2c only seemed to have the
      capacity to respond to Cd. CONCLUSIONS: A novel method to estimate the apparent
      kM for sulfate, avoiding the use of radiotracers, revealed that BjSultr1;1 and
      BjSultr1;2a/b/c are fully functional high-affinity sulfate transporters. The
      different behavior of the three BjSultr1;2 variants following Cd exposure or
      sulfate limitation suggests the existence of at least two distinct signal
      transduction pathways controlling root sulfate uptake in dissimilar nutritional
      and metabolic states.

PMID- 24884750
TI  - STABLE results: warfarin home monitoring achieves excellent INR control.
AB  - OBJECTIVES: Point-of-care, home international normalized ratio (INR) monitoring
      (patient self-testing, or PST) provides an opportunity to optimize warfarin
      therapy as demonstrated in randomized trials. This study sought to determine the
      quality of warfarin therapy as determined by time in therapeutic INR range (TTR)
      in patients who perform home monitoring outside of a clinical trial setting.
      STUDY DESIGN: Retrospective analysis. METHODS: The data base of an independent
      diagnostic testing facility was retrospectively queried over a 2.5-year period
      (January 2008-June 2011) and patient TTR was analyzed based on frequency of
      testing, age, gender, indication for therapy, duration of therapy, and critical
      value occurrence. RESULTS: A total of 29,457 patients with multiple indications
      for warfarin therapy comprised the database. The mean TTR for the entire group
      was 69.7%, with weekly testers achieving a TTR of 74% versus 68.9% for variable
      testers (testing every 2-4 weeks)(P <.0001). In all categories analyzed (age,
      indication for anticoagulation, and referral site volume), weekly testers
      performed significantly better than variable testers. Older individuals had a
      higher TTR than younger patients. Weekly testers experienced significantly fewer
      critical values (INR <1.5 or >5.0) than did variable testers. CONCLUSIONS: Point
      of-care patient self-testing at home achieves high-quality warfarin therapy
      outside of clinical trials and compares favorably with the results achieved in
      randomized trials or in anticoagulation clinic settings.

PMID- 24884751
TI  - Do strict formularies replicate failure for patients with schizophrenia?
AB  - OBJECTIVES: We measure the impact of Medicaid formulary restrictions (FRs) on the
      rate at which patients who previously failed a drug therapy for schizophrenia are
      returned to that therapy. STUDY DESIGN: We collect drug-level information on FRs
      in state Medicaid programs and examine claims of noninstitutionalized Medicaid
      enrollees with schizophrenia. METHODS: A difference-in-differences technique is
      used to compute the change in the probability of adverse outcomes before and
      after a state adopts an FR. This change is compared with the change in failure
      probabilities in states with no FRs. RESULTS: Regardless of FRs, patients tend to
      resume the same drug after an adverse medical event. In 2005, 69% of inpatient
      mental health-related admissions resulted in patients resuming the same therapy
      within 6 months of the event, and 63% of patients resumed the same drug after a
      mental health-related emergency department admission. In states where FRs limit
      access to all atypicals, the likelihood of a patient resuming the same atypical
      after having ceased treatment for at least 30 days increases by 20.1% relative to
      patients in states without restrictions. Additionally, patients in states that
      impose FRs on all atypicals are 11.6% more likely to discontinue all treatments.
      CONCLUSIONS: FR may increase the likelihood that patients will return to failed
      treatments or cease treatment altogether. Although formularies are designed to
      reduce drug spending, an unintended consequence may be an increase in the use of
      other services needed to treat patients with schizophrenia.

PMID- 24884753
TI  - Cost-effectiveness of a peer and practice staff support intervention.
AB  - OBJECTIVES: We examined the cost-effectiveness of an intervention to reduce
      coronary heart disease (CHD) risk and blood pressure in African Americans. STUDY
      DESIGN: Stochastic cost-effectiveness analysis alongside a clinical trial,
      augmented by a Markov model of lifetime cost-effectiveness. METHODS: In 2 urban
      academic primary care practices, we randomized African American patients with
      uncontrolled hypertension to a 6-month intervention of office practice and peer
      coach behavioral support (N = 136) or informational brochures about CHD risk
      factors (N = 144). Costs were estimated from the perspective of the provider.
      Outcomes included estimated CHD events avoided over 6 months and reduction in
      systolic blood pressure (SBP) (mm Hg). Subgroup analysis was performed for
      compliers who received an "effective" dose of the peer coach and office staff
      visits. Long-term cost-effectiveness was estimated by applying the clinical trial
      cost and effectiveness into a Markov model of CHD risk. RESULTS: The average cost
      for the behavioral support intervention group was $435.36 compared with $74.39
      for the brochure control group. The incremental cost-effectiveness ratio (ICER)
      was $47 per mm Hg reduction in SBP and $453,419 per CHD event avoided in 6
      months. Modeled over a 10-year horizon, the intervention had an ICER only as high
      as $3998 per incremental quality-adjusted life-year. CONCLUSIONS: A community
      primary care practice behavioral intervention to reduce hypertension in African
      Americans with sustained uncontrolled hypertension does not appear to be cost
      effective in the first 6 months. If intervention results are sustained over the
      long term, the program may be cost-effective over the patient's lifetime.

PMID- 24884752
TI  - Beyond black and white: race/ethnicity and health status among older adults.
AB  - OBJECTIVES: This study examined physical and mental health, health symptoms,
      sensory and functional limitations, risk factors, and multimorbidity among older
      Medicare managed care members to assess disparities associated with
      race/ethnicity. STUDY DESIGN AND METHODS: We used data on 236,289 older adults
      from 208 Medicare plans who completed the 2012 Medicare Health Outcomes Survey to
      compare 14 health indicators across non-Hispanic whites, blacks, American
      Indians/Alaskan Natives, Asians, Native Hawaiians/Pacific Islanders, multiracial
      individuals, and Hispanics. Logistic regression models that clustered on the plan
      estimated the risk of indicators of adverse health and functional status.
      RESULTS: Even after controlling for key patient sociodemographic factors,
      race/ethnicity was significantly associated with most adverse health indicators.
      Except for Asians, all racial/ethnic minority groups were significantly more
      likely than whites to report poor mental health status, presence of most health
      symptoms, sensory limitations, and activities-of-daily-living disability.
      Important differences were observed across racial and ethnic groups. CONCLUSIONS:
      Despite some exceptions, elders of racial/ethnic minority background are
      generally at higher risk than non-Hispanic whites for a broad range of adverse
      health and functional outcomes that are not routinely assessed. Limitations
      include bias related to self-reported data and respondent recall. Future research
      should consider ethnic subgroup variations; employing newer techniques to improve
      estimates for smaller groups; and prioritizing and identifying opportunities for
      care improvement of diverse enrollee groups by considering specific needs. To
      improve the health status of the elderly, service delivery targeting the needs of
      specific population groups, coupled with culturally appropriate care for racial/
      ethnic minorities, should also be considered.

PMID- 24884754
TI  - Mobile health clinics in the era of reform.
AB  - OBJECTIVES: Despite the role of mobile clinics in delivering care to the full
      spectrum of at-risk populations, the collective impact of mobile clinics has
      never been assessed. This study characterizes the scope of the mobile clinic
      sector and its impact on access, costs, and quality. It explores the role of
      mobile clinics in the era of delivery reform and expanded insurance coverage.
      STUDY DESIGN: A synthesis of observational data collected through Mobile Health
      Map and published literature related to mobile clinics. METHODS: Analysis of data
      from the Mobile Health Map Project, an online platform that aggregates data on
      mobile health clinics in the United States, supplemented by a comprehensive
      literature review. RESULTS: Mobile clinics represent an integral component of the
      healthcare system that serves vulnerable populations and promotes high-quality
      care at low cost. There are an estimated 1500 mobile clinics receiving 5 million
      visits nationwide per year. Mobile clinics improve access for vulnerable
      populations, bolster prevention and chronic disease management, and reduce costs.
      Expanded coverage and delivery reform increase opportunities for mobile clinics
      to partner with hospitals, health systems, and insurers to improve care and lower
      costs. CONCLUSIONS: Mobile clinics have a critical role to play in providing high
      quality, low-cost care to vulnerable populations. The postreform environment,
      with increasing accountability for population health management and expanded
      access among historically underserved populations, should strengthen the ability
      for mobile clinics to partner with hospitals, health systems, and payers to
      improve care and lower costs.

PMID- 24884755
TI  - Interruption in physical activity bout analysis: an accelerometry research issue.
AB  - BACKGROUND: The purpose of the present investigation was to clarify the impact of
      the treatment of interruptions on the durations and the frequency of the physical
      activity (PA) bouts under free-living conditions. METHODS: One hundred and forty
      adults (50 +/- 7 years) wore an accelerometer (Lifecorder) for seven consecutive
      days under free-living conditions. According to the minutes by minutes metabolic
      equivalents (METs) value, the PA was divided into one of three intensity
      categories: light intensity PA (LPA, < 3 METs), moderate intensity PA (MPA, 3 to
      6 METs), vigorous intensity PA (VPA, > 6 METs), and the sum of the MPA and VPA
      was defined as moderate to vigorous intensity PA (MVPA, > 3 METs). Thereafter,
      based on the time series data, we defined MVPA bouts as PA that was maintained at
      no less than 3 METs completely for 10 minutes or longer with or without allowing
      for a one-minute or a two-minute break (<3METs). RESULTS: The frequency and
      duration of the continuous MVPA bouts lasting longer than 10-min were
      significantly lower and shorter compared with that in the non-continuous MVPA
      bouts allowing a one- or two-minute interruption (4.11 +/- 1.65, 6.58 +/- 2.72
      and 8.97 +/- 3.55 bouts/day, 71.62 +/- 33.66, 119.03 +/- 49.35 and 169.75 +/-
      65.87 min/day, P < 0.05). The number of days with a total time of MVPA bouts of
      30-min was significantly lower in the continuous MVPA bouts compared with that in
      the non-continuous MVPA bouts allowing a 1-min or 2-min interruption (5.36 +/-
      1.65, 6.39 +/- 1.07 and 6.65 +/- 0.85 days/week). CONCLUSION: The treatment of
      interruptions for the setting of the accelerometer affects the estimation of the
      MVPA bouts under free-living conditions in middle-aged to older adults. The best
      analysis process with regard to the accelerometer quantifying the break to
      reflect the real behavioral pattern and the physiological stress in such subjects
      remains unclear.

PMID- 24884757
TI  - Interprofessional practices of physiotherapists working with adults with low back
      pain in Quebec's private sector: results of a qualitative study.
AB  - BACKGROUND: Collaboration and interprofessional practices are highly valued in
      health systems, because they are thought to improve outcomes of care for persons
      with complex health problems, such as low back pain. Physiotherapists, like all
      health providers, are encouraged to take part in interprofessional practices.
      However, little is known about these practices, especially for private sector
      physiotherapists. This study aimed to: 1) explore how physiotherapists working in
      the private sector with adults with low back pain describe their
      interprofessional practices, 2) identify factors that influence their
      interprofessional practices, and 3) identify their perceived effects. METHODS:
      Participants were 13 physiotherapists, 10 women/3 men, having between 3 and 21
      years of professional experience. For this descriptive qualitative study, we used
      face-to-face semi-structured interviews and conducted content analysis
      encompassing data coding and thematic regrouping. RESULTS: Physiotherapists
      described interprofessional practices heterogeneously, including numerous
      processes such as sharing information and referring. Factors that influenced
      physiotherapists' interprofessional practices were related to patients,
      providers, organizations, and wider systems (e.g. professional system).
      Physiotherapists mostly viewed positive effects of interprofessional practices,
      including elements such as gaining new knowledge as a provider and being valued
      in one's own role, as well as improvements in overall treatment and outcome.
      CONCLUSIONS: This qualitative study offers new insights into the
      interprofessional practices of physiotherapists working with adults with low back
      pain, as perceived by the physiotherapists' themselves. Based on the results, the
      development of strategies aiming to increase interprofessionalism in the
      management of low back pain would most likely require taking into consideration
      factors associated with patients, providers, the organizations within which they
      work, and the wider systems.

PMID- 24884758
TI  - What factors influence the metal-proton spin-spin coupling constants in mercury-
      and cadmium-substutited rubredoxin?
AB  - The indirect metal-proton spin-spin coupling constants between protons in
      cysteine groups and the mercury or cadmium nucleus have been calculated for a
      small model of Me-rubredoxin complex (Me = Cd, Hg) by means of density functional
      theory with zeroth-order regular approximation Hamiltonian (DFT-ZORA). The
      calculated spin-spin coupling constants, in spite of the moderate size of the
      model system, are in good agreement with the values measured in NMR experiment,
      which are in the 0.29-0.56 Hz range for the Cd complex and in the 0.57-2.20 Hz
      range for the Hg complex. The robustness of the chosen method has been verified
      by calculations with a number of different exchange-correlation functionals and
      basis sets. Additionally, it has been shown that the short- and long-distance
      metal-proton coupling constants are affected mainly by the values of the metal
      proton distance and the H-N-C-C dihedral angle. 

PMID- 24884756
TI  - RNA-binding protein RNPC1: acting as a tumor suppressor in breast cancer.
AB  - BACKGROUND: RNA binding proteins (RBPs) play a fundamental role in
      posttranscriptional control of gene expression. Different RBPs have oncogenic or
      tumor-suppressive functions on human cancers. RNPC1 belongs to the RNA
      recognition motif (RRM) family of RBPs, which could regulate expression of
      diverse targets by mRNA stability in human cancer cells. Several studies reported
      that RNPC1 played an important role in cancer, mostly acting as an oncogene or up
      regulating in tumors. However, its role in human breast cancer remains unclear.
      METHODS: In the present study, we investigated the functional and mechanistic
      roles of RNPC1 in attenuating invasive signal including reverse epithelial
      mesenchymal transition (EMT) to inhibit breast cancer cells aggressiveness in
      vitro. Moreover, RNPC1 suppress tumorigenicity in vivo. Further, we studied the
      expression of RNPC1 in breast cancer tissue and adjacent normal breast tissue by
      quantitative RT-PCR (qRT-PCR) and Western blot. RESULTS: We observed that RNPC1
      expression was silenced in breast cancer cell lines compared to breast epithelial
      cells. More important, RNPC1 was frequently silenced in breast cancer tissue
      compared to adjacent normal breast tissue. Low RNPC1 mRNA expression was
      associated with higher clinical stages and mutp53, while low level of RNPC1
      protein was associated with higher lymph node metastasis, mutp53 and lower
      progesterone receptor (PR). Functional assays showed ectopic expression of RNPC1
      could inhibit breast tumor cell proliferation in vivo and in vitro through
      inducing cell cycle arrest, and further suppress tumor cell migration and
      invasion partly through repressing mutant p53 (mutp53) induced EMT. CONCLUSIONS:
      Overall, our findings indicated that RNPC1 had a potential function to play a
      tumor-suppressor role which may be a potential marker in the therapeutic and
      prognostic of breast cancer.

PMID- 24884759
TI  - Individual and community determinants of neonatal mortality in Ghana: a
      multilevel analysis.
AB  - BACKGROUND: Neonatal mortality is a global challenge; identification of
      individual and community determinants associated with it are important for
      targeted interventions. However in most low and middle income countries (LMICs)
      including Ghana this problem has not been adequately investigated as the impact
      of contextual factors remains undetermined despite their significant influence on
      under-five mortality and morbidity. METHODS: Based on a modified conceptual
      framework for child survival, hierarchical modelling was deployed to examine
      about 6,900 women, aged 15 - 49 years (level 1), nested within 412 communities
      (level 2) in Ghana by analysing combined data of the 2003 and 2008 Ghana
      Demographic and Health Survey. The aim was to identify individual (maternal,
      paternal, neonatal, antenatal, delivery and postnatal) and community
      (socioeconomic disadvantage communities) determinants associated with neonatal
      mortality. RESULTS: The results showed both individual and community
      characteristics to be associated with neonatal mortality. Infants of multiple
      gestation [OR 5.30; P-value < 0.001; 95% CI 2.81 - 10.00], neonates with
      inadequate birth spacing [OR 3.47; P-value < 0.01; 95% CI 1.60 - 7.57] and low
      birth weight [OR 2.01; P-value < 0.01; 95% CI 1.23 - 3.30] had a lower chance of
      surviving the neonatal period. Similarly, infants of grand multiparous mothers
      [OR 2.59; P-value < 0.05; 95% CI 1.03 - 6.49] and non-breastfed infants [OR
      142.31; P-value < 0.001; 95% CI 80.19 - 252.54] were more likely to die during
      neonatal life, whereas adequate utilization of antenatal, delivery and postnatal
      health services [OR 0.25; P-value < 0.001; 95% CI 0.13 - 0.46] reduced the
      likelihood of neonatal mortality. Dwelling in a neighbourhood with high
      socioeconomic deprivation was associated with increased neonatal mortality [OR
      3.38; P-value < 0.01; 95% CI 1.42 - 8.04]. CONCLUSION: Both individual and
      community characteristics show a marked impact on neonatal survival.
      Implementation of community-based interventions addressing basic education,
      poverty alleviation, women empowerment and infrastructural development and an
      increased focus on the continuum-of-care approach in healthcare service will
      improve neonatal survival.

PMID- 24884760
TI  - Electronic excitations in graphene in the 1-50 eV range: the pi and pi + sigma
      peaks are not plasmons.
AB  - The field of plasmonics relies on light coupling strongly to plasmons as
      collective excitations. The energy loss function of graphene is dominated by two
      peaks at ~5 and ~15 eV, known as pi and pi + sigma plasmons, respectively. We use
      electron energy-loss spectroscopy in an aberration-corrected scanning
      transmission electron microscope and density functional theory to show that
      between 1 to 50 eV, these prominent pi and pi + sigma peaks are not plasmons, but
      single-particle interband excitations.

PMID- 24884761
TI  - Nested PCR detection of malaria directly using blood filter paper samples from
      epidemiological surveys.
AB  - BACKGROUND: Nested PCR is considered a sensitive and specific method for
      detecting malaria parasites and is especially useful in epidemiological surveys.
      However, the preparation of DNA templates for PCR is often time-consuming and
      costly. METHODS: A simplified PCR method was developed to directly use a small
      blood filter paper square (2 * 2 mm) as the DNA template after treatment with
      saponin. This filter paper-based nested PCR method (FP-PCR) was compared to
      microscopy and standard nested PCR with DNA extracted by using a Qiagen DNA mini
      kit from filter paper blood spots of 204 febrile cases. The FP-PCR technique was
      further applied to evaluate malaria infections in 1,708 participants from cross
      sectional epidemiological surveys conducted in Myanmar and Thailand. RESULTS: The
      FP-PCR method had a detection limit of ~0.2 parasites/MUL blood, estimated using
      cultured Plasmodium falciparum parasites. With 204 field samples, the sensitivity
      of the FP-PCR method was comparable to that of the standard nested PCR method,
      which was significantly higher than that of microscopy. Application of the FP-PCR
      method in large cross-sectional studies conducted in Myanmar and Thailand
      detected 1.9% (12/638) and 6.2% (66/1,070) asymptomatic Plasmodium infections,
      respectively, as compared to the detection rates of 1.3% (8/638) and 0.04%
      (4/1,070) by microscopy. CONCLUSION: This FP-PCR method was much more sensitive
      than microscopy in detecting Plasmodium infections. It drastically increased the
      detection sensitivity of asymptomatic infections in cross-sectional surveys
      conducted in Thailand and Myanmar, suggesting that this FP-PCR method has a
      potential for future applications in malaria epidemiology studies.

PMID- 24884763
TI  - Substitution of physicians by nurses in primary care: a systematic review and
      meta-analysis.
AB  - BACKGROUND: In many countries, substitution of physicians by nurses has become
      common due to the shortage of physicians and the need for high-quality,
      affordable care, especially for chronic and multi-morbid patients. We examined
      the evidence on the clinical effectiveness and care costs of physician-nurse
      substitution in primary care. METHODS: We systematically searched OVID Medline
      and Embase, The Cochrane Library and CINAHL, up to August 2012; selected and
      critically appraised published randomised controlled trials (RCTs) that compared
      nurse-led care with care by primary care physicians on patient satisfaction,
      Quality of Life (QoL), hospital admission, mortality and costs of healthcare. We
      assessed the individual study risk of bias, calculated the study-specific and
      pooled relative risks (RR) or standardised mean differences (SMD); and performed
      fixed-effects meta-analyses. RESULTS: 24 RCTs (38,974 participants) and 2
      economic studies met the inclusion criteria. Pooled analyses showed higher
      overall scores of patient satisfaction with nurse-led care (SMD 0.18, 95% CI 0.13
      to 0.23), in RCTs of single contact or urgent care, short (less than 6 months)
      follow-up episodes and in small trials (N <= 200). Nurse-led care was effective
      at reducing the overall risk of hospital admission (RR 0.76, 95% CI 0.64 to
      0.91), mortality (RR 0.89, 95% CI 0.84 to 0.96), in RCTs of on-going or non
      urgent care, longer (at least 12 months) follow-up episodes and in larger (N >
      200) RCTs. Higher quality RCTs (with better allocation concealment and less
      attrition) showed higher rates of hospital admissions and mortality with nurse
      led care albeit less or not significant. The results seemed more consistent
      across nurse practitioners than with registered or licensed nurses. The effects
      of nurse-led care on QoL and costs were difficult to interpret due to
      heterogeneous outcome reporting, valuation of resources and the small number of
      studies. CONCLUSIONS: The available evidence continues to be limited by the
      quality of the research considered. Nurse-led care seems to have a positive
      effect on patient satisfaction, hospital admission and mortality. This important
      finding should be confirmed and the determinants of this effect should be
      assessed in further, larger and more methodically rigorous research.

PMID- 24884762
TI  - Critical role of inflammatory cytokines in impairing biochemical processes for
      learning and memory after surgery in rats.
AB  - BACKGROUND: Patients with postoperative cognitive dysfunction have poor outcomes.
      Neuroinflammation may be the underlying pathophysiology for this dysfunction. We
      determined whether proinflammatory cytokines affect the trafficking of alpha
      amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors to the plasma
      membrane, a fundamental biochemical process for learning and memory. METHODS:
      Four-month-old male Fischer 344 rats were subjected to right carotid exposure
      under isoflurane anesthesia. Some rats received intravenous lidocaine infusion
      during anesthesia. Rats were tested two weeks later by Barnes maze. The
      hippocampus was harvested six hours after the surgery for western blotting of
      interleukin (IL)-1beta or IL-6. Hippocampal slices were prepared from control
      rats or rats subjected to surgery two weeks previously. They were incubated with
      tetraethylammonium, an agent that can induce long term potentiation, for
      determining the trafficking of GluR1, an alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid receptor subunit. RESULTS: Surgery or anesthesia
      increased the time to identify the target box during the Barnes maze test
      training sessions and one day after the training sessions. Surgery also prolonged
      the time to identify the target box eight days after the training sessions.
      Surgery increased IL-1beta and IL-6 in the hippocampus. The tetraethylammonium
      induced GluR1 phosphorylation and trafficking were abolished in the hippocampal
      slices of rats after surgery. These surgical effects were partly inhibited by
      lidocaine. The incubation of control hippocampal slices with IL-1beta and IL-6
      abolished tetraethylammonium-induced GluR1 trafficking and phosphorylation.
      Lidocaine minimally affected the effects of IL-1beta on GluR1 trafficking.
      CONCLUSIONS: Our results suggest that surgery increases proinflammatory cytokines
      that then inhibit GluR1 trafficking, leading to learning and memory impairment.

PMID- 24884765
TI  - Headache yesterday in Europe.
AB  - BACKGROUND: Surveys enquiring about burden of headache over a prior period of
      time (e.g., 3 months) are subject to recall bias. To eliminate this as far as
      possible, we focused on presence and impact of headache on the preceding day
      ("headache yesterday"). METHODS: Adults (18-65 years) were surveyed from the
      general populations of Germany, Italy, Lithuania, Luxembourg and the Netherlands,
      from a work-force population in Spain and from mostly non-headache patient
      populations of Austria, France and U.K. A study of non-responders in some
      countries allowed detection of potential participation bias where initial
      participation rates were low. RESULTS: Participation rates varied between 11% and
      59% (mean 27%). Non-responder studies suggested that, because of participation
      bias, headache prevalence might be overestimated in initial responders by up to
      2% (absolute). Across all countries, 1,422 of 8,271 participants (15-17%,
      depending on correction for participation bias) had headache yesterday lasting on
      average for 6 hours. It was bad or very bad in 56% of cases and caused absence
      from work or school in 6%. Among those who worked despite headache, 20% reported
      productivity reduced by >50%. Social activities were lost by 24%. Women (21%)
      were more likely than men (12%) to have headache yesterday, but impact was
      similar in the two genders. CONCLUSIONS: With recall biases avoided, our findings
      indicate that headache costs at least 0.7% of working capacity in Europe. This
      calculation takes into account that most of those who missed work could make up
      for this later, which, however, means that leisure and social activities are even
      more influenced by headache.

PMID- 24884764
TI  - Secondary bile acids: an underrecognized cause of colon cancer.
AB  - Bile acids were first proposed as carcinogens in 1939. Since then, accumulated
      evidence has linked exposure of cells of the gastrointestinal tract to repeated
      high physiologic levels of bile acids as an important risk factor for
      gastrointestinal cancers. High exposure to bile acids may occur in a number of
      settings, but most importantly, is prevalent among individuals who have a high
      dietary fat intake. A rapid effect on cells of high bile acid exposure is the
      generation of reactive oxygen species and reactive nitrogen species, disruption
      of the cell membrane and mitochondria, induction of DNA damage, mutation and
      apoptosis, and development of reduced apoptosis capability upon chronic exposure.
      Here, we review the substantial evidence of the mechanism of secondary bile acids
      and their role in colon cancer.

PMID- 24884766
TI  - Differential gene expression between functionally specialized polyps of the
      colonial hydrozoan Hydractinia symbiolongicarpus (Phylum Cnidaria).
AB  - BACKGROUND: A colony of the hydrozoan Hydractinia symbiolongicarpus comprises
      genetically identical yet morphologically distinct and functionally specialized
      polyp types. The main labor divisions are between feeding, reproduction and
      defense. In H. symbiolongicarpus, the feeding polyp (called a gastrozooid) has
      elongated tentacles and a mouth, which are absent in the reproductive polyp
      (gonozooid) and defensive polyp (dactylozooid). Instead, the dactylozooid has an
      extended body column with an abundance of stinging cells (nematocysts) and the
      gonozooid bears gonophores on its body column. Morphological differences between
      polyp types can be attributed to simple changes in their axial patterning during
      development, and it has long been hypothesized that these specialized polyps
      arose through evolutionary alterations in oral-aboral patterning of the ancestral
      gastrozooid. RESULTS: An assembly of 66,508 transcripts (>200 bp) were generated
      using short-read Illumina RNA-Seq libraries constructed from feeding,
      reproductive, and defensive polyps of H. symbiolongicarpus. Using several
      different annotation methods, approximately 54% of the transcripts were
      annotated. Differential expression analyses were conducted between these three
      polyp types to isolate genes that may be involved in functional, histological,
      and pattering differences between polyp types. Nearly 7 K transcripts were
      differentially expressed in a polyp-specific manner, including members of the
      homeodomain, myosin, toxin and BMP gene families. We report the spatial
      expression of a subset of these polyp-specific transcripts to validate our
      differential expression analyses. CONCLUSIONS: While potentially originating
      through simple changes in patterning, polymorphic polyps in Hydractinia are the
      result of differentially expressed functional, structural, and patterning
      genes.The differentially expressed genes identified in our study provide a
      starting point for future investigations of the developmental patterning and
      functional differences that are displayed in the different polyp types that
      confer a division of labor within a colony of H. symbiolongicarpus.

PMID- 24884767
TI  - Detection and genetic analysis of the enteroaggregative Escherichia coli heat
      stable enterotoxin (EAST1) gene in clinical isolates of enteropathogenic
      Escherichia coli (EPEC) strains.
AB  - BACKGROUND: The enteroaggregative E. coli heat-stable enterotoxin 1 (EAST1)
      encoded by astA gene has been found in enteropathogenic E. coli (EPEC) strains.
      However, it is not sufficient to simply probe strains with an astA gene probe due
      to the existence of astA mutants (type 1 and type 2 SHEAST) and EAST1 variants
      (EAST1 v1-4). In this study, 222 EPEC (70 typical and 152 atypical) isolates were
      tested for the presence of the astA gene sequence by PCR and sequencing. RESULTS:
      The astA gene was amplified from 54 strains, 11 typical and 43 atypical. Sequence
      analysis of the PCR products showed that 25 strains, 7 typical and 18 atypical,
      had an intact astA gene. A subgroup of 7 atypical strains had a variant type of
      the astA gene sequence, with four non-synonymous nucleotide substitutions. The
      remaining 22 strains had mutated astA gene with nucleotide deletions or
      substitutions in the first 8 codons. The RT-PCR results showed that the astA gene
      was transcribed only by the strains carrying either the intact or the variant
      type of the astA gene sequence. Southern blot analysis indicated that astA is
      located in EAF plasmid in typical strains, and in plasmids of similar size in
      atypical strains. Strains carrying intact astA genes were more frequently found
      in diarrheic children than in non-diarrheic children (p < 0.05). CONCLUSION: In
      conclusion, our data suggest that the presence of an intact astA gene may
      represent an additional virulence determinant in both EPEC groups.

PMID- 24884768
TI  - Incidental finding of carcinoid tumor on Meckel's diverticulum: case report and
      literature review, should prophylactic resection be recommended?
AB  - Meckel's diverticulum (MD) is the most common congenital anomaly of the
      gastrointestinal tract and is caused by incomplete obliteration of the vitelline
      duct during intrauterine life. MD affects less than 2% of the population. In most
      cases, MD is asymptomatic and the estimated average complication risk of MD
      carriers, which is inversely proportional to age, ranges between 2% and 4%. The
      most common MD-related complications are gastrointestinal bleeding, intestinal
      obstruction and acute phlogosis. Excision is mandatory in the case of symptomatic
      diverticula regardless of age, while surgical treatment for asymptomatic
      diverticula remains controversial. According to the majority of studies, the
      incidental finding of MD in children is an indication for surgical resection,
      while the management of adults is not yet unanimous. In this case report, we
      describe the prophylactic resection of an incidentally detected MD, which led to
      the removal of an occult mucosal carcinoid tumor. In literature, the association
      of MD and carcinoid tumor is reported as a rare finding. Even though the strategy
      for adult patients of an incidental finding of MD during surgery performed for
      other reasons divides the experts, we recommend prophylactic excision in order to
      avoid any further risk. 

PMID- 24884769
TI  - Plasma levels of the pro-inflammatory protein S100A12 (EN-RAGE) are associated
      with muscle and fat mass in hemodialysis patients: a cross-sectional study.
AB  - BACKGROUND: Malnutrition is highly prevalent and contributes to mortality in
      hemodialysis (HD) patients. Although the receptor for advanced glycation end
      products (RAGE) system also contributes to the morbidity and mortality of these
      patients, the role that the RAGE system plays in determining nutritional status
      is currently unknown. METHODS: A cross-sectional study examining 79 HD patients
      was performed. The plasma concentrations of the soluble RAGE (sRAGE) and S100A12
      (also known as EN-RAGE) were studied to evaluate their association with
      nutritional status, which was assessed by measuring the mid-thigh muscle mass and
      subcutaneous fat mass with computed tomography. RESULTS: Plasma S100A12
      concentrations were shown to be significantly and negatively correlated with
      muscle mass and with fat mass (r = -0.237, P < 0.05 and r = -0.261, P < 0.05,
      respectively). In contrast, sRAGE was not shown to significantly correlate with
      either of these factors. Multiple regression analyses demonstrated that S100A12
      is a significant independent predictor of both muscle mass and fat mass (P < 0.01
      and P < 0.05, respectively). CONCLUSIONS: Our findings suggest that plasma
      S100A12 levels could play an important role in determining muscle mass and fat
      mass in HD patients. TRIAL REGISTRATION: Study number; UMIN000012341.

PMID- 24884770
TI  - Mesh Or Patch for Hernia on Epigastric and Umbilical Sites (MORPHEUS trial):
      study protocol for a multi-centre patient blinded randomized controlled trial.
AB  - BACKGROUND: Evidence is accumulating that, similar to other ventral hernias,
      umbilical and epigastric hernias must be mesh repaired. The difficulties involved
      in mesh placement and in mesh-related complications could be the reason many
      small abdominal hernias are still primary closed. In laparoscopic repair, a mesh
      is placed intraperitoneally, while the most common procedure is open surgery is
      pre-peritoneal mesh placement. A recently developed alternative method is the so
      called patch repair, in this approach a mesh can be placed intraperitoneally
      through open surgery. In theory, such patches are particularly suitable for small
      hernias due to a reduction in the required dissection. This simple procedure is
      described in several studies. It is still unclear whether this new approach is
      associated with an equal risk of recurrence and complications compared with pre
      peritoneal meshes. The material of the patch is in direct contact with intra
      abdominal organs, it is unknown if this leads to more complications. On the other
      hand, the smaller dissection in the pre-peritoneal plane may lead to a reduction
      in wound complications. METHODS/DESIGN: 346 patients suffering from an umbilical
      or epigastric hernia will be included in a multi-centre patient-blinded trial,
      comparing mesh repair with patch repair. Randomisation will take place for the
      two operation techniques. The two devices investigated are a flat pre-peritoneal
      mesh and a Proceed Ventral Patch(r). Stratification will occur per centre. Post
      operative evaluation will take place after 1, 3, 12 and 24 months. The number of
      complications requiring treatment is the primary endpoint. Secondary endpoints
      are Verbal Descriptor Scale (VDS) pain score and VDS cosmetic score, operation
      duration, recurrence and costs. An intention to treat analysis will be performed.
      DISCUSSION: This trial is one of the first in its kind, to compare different mesh
      devices in a randomized controlled setting. The results will help to evaluate
      mesh repair for epigastric an umbilical hernia, and find a surgical method that
      minimizes the complication rate. TRIAL REGISTRATION: Netherlands Trail
      Registration (NTR) www.trialregister.nl 2010 NTR2514 NL33995.060.10.

PMID- 24884771
TI  - Density of the midpalatal suture after RME treatment - a retrospective
      comparative low-dose CT-study.
AB  - INTRODUCTION: Rapid maxillary expansion (RME) is a common technique to improve
      the dental and skeletal transverse width in cases of constricted maxillary
      arches. Although retention after RME has been widely examined, there is still no
      clear statement about the minimal retention time in postpubertal patients and
      many practitioners have retention concepts varying between three and six months.
      METHODS: This retrospective study consisted of 14 patients who were either
      treated with a Haas-type RME (6 patients) or a Hybrid-RME (8 patients). The
      average age was 15.8 years (min. 13.5 years, max. 23.0 years).Low-dose CT scans
      were taken initially before placement of the RME (T0), directly after maximal
      activation (T1) and (in six cases) also in retention after 6 months (T2). Using a
      3D-software ("OnDemand3D"/Cybermed Inc.) in analogy to the method published by
      Franchi et al. (AJODO Volume 137/ Number 4) all values were measured twice at an
      interval of 1 month to assess the method error and the intraoperator
      reliability.Statistical analysis was performed using SPSS 21 for Mac. Possible
      influences of the RME-type were assessed using the univariate ANOVA. Changes in
      the sutural density between the different points of time were examined using
      paired t-tests. RESULTS: The density of the suture decreased significantly after
      expansion (T0-T1) with both types of RME (p = 0.000). In the retention period
      there was a significant increase of the sutural density (p = 0.007) although it
      did not achieve the initial level (p = 0.002). CONCLUSIONS: 1. The midpalatal
      suture was opened in all analysed patients.2. In postpubertal patients a
      retention time of six months does not allow sufficient reorganization of the
      suture.3. Therefore, a retention period longer than six months seems to be
      beneficial to prevent relapses in postpubertal patients.

PMID- 24884772
TI  - Critical role of cellular cholesterol in bovine rotavirus infection.
AB  - BACKGROUND: Bovine rotavirus (BRV) is a non-enveloped dsRNA virus that cause
      neonatal calf diarrhea. Lipid rafts are cholesterol-enrich membrane mircodomains
      that play a vital role in many cellular processes. In this study, the effect of
      cellular cholesterol depletion on infection of MA-104 cells with bovine rotavirus
      was investigated. RESULTS: We demonstrated that cholesterol depletion of the
      plasma membrane by MbetaCD had no effect on BRV binding to cells but
      significantly impaired BRV entry in a dose-dependent manner and the effect was
      partially reversed by addition of exogenous cholesterol, suggesting the reduction
      of BRV infection by MbetaCD was specifically due to cholesterol depletion.
      Cholesterol depletion after virus entry did not reduce BRV replication, whereas
      affected virus assembly. CONCLUSIONS: Taken together, our results demonstrate
      that cell membrane cholesterol is essential to BRV infectivity.

PMID- 24884773
TI  - Whole brain radiotherapy plus simultaneous in-field boost with image guided
      intensity-modulated radiotherapy for brain metastases of non-small cell lung
      cancer.
AB  - BACKGROUND: Whole brain radiotherapy (WBRT) plus sequential focal radiation boost
      is a commonly used therapeutic strategy for patients with brain metastases.
      However, recent reports on WBRT plus simultaneous in-field boost (SIB) also
      showed promising outcomes. The objective of present study is to retrospectively
      evaluate the efficacy and toxicities of WBRT plus SIB with image guided intensity
      modulated radiotherapy (IG-IMRT) for inoperable brain metastases of NSCLC.
      METHODS: Twenty-nine NSCLC patients with 87 inoperable brain metastases were
      included in this retrospective study. All patients received WBRT at a dose of 40
      Gy/20 f, and SIB boost with IG-IMRT at a dose of 20 Gy/5 f concurrent with WBRT
      in the fourth week. Prior to each fraction of IG-IMRT boost, on-line positioning
      verification and correction were used to ensure that the set-up errors were
      within 2 mm by cone beam computed tomography in all patients. RESULTS: The one
      year intracranial control rate, local brain failure rate, and distant brain
      failure rate were 62.9%, 13.8%, and 19.2%, respectively. The two-year
      intracranial control rate, local brain failure rate, and distant brain failure
      rate were 42.5%, 30.9%, and 36.4%, respectively. Both median intracranial
      progression-free survival and median survival were 10 months. Six-month, one
      year, and two-year survival rates were 65.5%, 41.4%, and 13.8%, corresponding to
      62.1%, 41.4%, and 10.3% of intracranial progression-free survival rates. Patients
      with Score Index for Radiosurgery in Brain Metastases (SIR) >5, number of
      intracranial lesions <3, and history of EGFR-TKI treatment had better survival.
      Three lesions (3.45%) demonstrated radiation necrosis after radiotherapy. Grades
      2 and 3 cognitive impairment with grade 2 radiation leukoencephalopathy were
      observed in 4 (13.8%) and 4 (13.8%) patients. No dosimetric parameters were found
      to be associated with these late toxicities. Patients received EGFR-TKI treatment
      had higher incidence of grades 2-3 cognitive impairment with grade 2
      leukoencephalopathy. CONCLUSIONS: WBRT plus SIB with IG-IMRT is a tolerable and
      effective treatment for NSCLC patients with inoperable brain metastases. However,
      the results of present study need to be examined by the prospective
      investigations.

PMID- 24884774
TI  - Vitamin D deficiency is common in psychogeriatric patients, independent of
      diagnosis.
AB  - BACKGROUND: Previous studies have found an association between psychiatric
      disorders and vitamin D deficiency, but most studies have focused on depression.
      This study aimed to establish the prevalence of vitamin D deficiency in elderly
      patients with a wider range of psychiatric diagnoses. METHOD: The study included
      elderly patients (>64 years) referred to a psychiatric hospital in Northern
      Norway and a control group from a population survey in the same area. An
      assessment of psychiatric and cognitive symptoms and diagnoses was conducted
      using the Montgomery and Aasberg Depression Rating Scale, the Cornell Scale for
      Depression in Dementia, the Mini Mental State Examination, the Clockdrawing Test,
      and the Mini International Neuropsychiatric Interview (MINI+), as well as
      clinical interviews and a review of medical records. The patients' mean level of
      25-hydroxyvitamin D (25(OH)D) and the prevalence of vitamin D deficiency were
      compared with those of a control group, and a comparison of vitamin D deficiency
      across different diagnostic groups was also made. Vitamin D deficiency was
      defined as 25(OH)D <50 nmol/L (<20 ng/ml). RESULTS: The mean levels of 25(OH)D in
      the patient group (n = 95) and the control group (n = 104) were 40.5 nmol/L and
      65.9 nmol/L (p < 0.001), respectively. A high prevalence of vitamin D deficiency
      was found in the patient group compared with the control group (71.6% and 20.0%,
      respectively; p < 0.001). After adjusting for age, gender, season, body mass
      index, and smoking, vitamin D deficiency was still associated with patient status
      (OR: 12.95, CI (95%): 6.03-27.83, p < 0.001). No significant differences in the
      prevalence of vitamin D deficiency were found between patients with different
      categories of psychiatric diagnoses, such as depression, bipolar disorders,
      psychosis, and dementia. CONCLUSION: Vitamin D deficiency is very common among
      psychogeriatric patients, independent of diagnostic category. Even though the
      role of vitamin D in psychiatric disorders is still not clear, we suggest
      screening for vitamin D deficiency in this patient group due to the importance of
      vitamin D for overall health.

PMID- 24884777
TI  - Retrospective diagnosis of a famous historical figure: ontological, epistemic,
      and ethical considerations.
AB  - The aim of this essay is to elaborate philosophical and ethical underpinnings of
      posthumous diagnosis of famous historical figures based on literary and artistic
      products, or commonly called retrospective diagnosis. It discusses ontological
      and epistemic challenges raised in the humanities and social sciences, and
      attempts to systematically reply to their criticisms from the viewpoint of
      clinical medicine, philosophy of medicine, particularly the ontology of disease
      and the epistemology of diagnosis, and medical ethics. The ontological challenge
      focuses on the doubt about the persistence of a disease over historical time,
      whereas the epistemic challenge disputes the inaccessibility of scientific
      verification of a diagnosis in the past. I argue that the critics are in error in
      conflating the taxonomy of disease (nosology) and the act of diagnosing a
      patient. Medical diagnosis is fundamentally a hypothesis-construction and an
      explanatory device that can be generated under various degrees of uncertainty and
      limited amount of information. It is not an apodictic judgment (true or false) as
      the critics presuppose, but a probabilistic (Bayesian) judgment with varying
      degrees of plausibility under uncertainty. In order to avoid this confusion, I
      propose that retrospective diagnosis of a historical figure be syndromic without
      identifying underlying disease, unless there is justifiable reason for such
      specification. Moreover it should be evaluated not only from the viewpoint of
      medical science but also in a larger context of the scholarship of the humanities
      and social sciences by its overall plausibility and consistency. On the other
      hand, I will endorse their concerns regarding the ethics and professionalism of
      retrospective diagnosis, and call for the need for situating such a diagnosis in
      an interdisciplinary scope and the context of the scholarship of the historical
      figure. I will then enumerate several important caveats for interdisciplinary
      retrospective diagnosis using an example of the retrospective diagnosis of
      Socrates for his life-long intermittent neurologic symptoms. Finally, I will
      situate the present argument in a larger context of the major debate among the
      historians of medicine and paleopathologists, and discuss the similarities and
      differences. 

PMID- 24884776
TI  - Distal end side-to-side anastomoses of sequential vein graft to small target
      coronary arteries improve intraoperative graft flow.
AB  - BACKGROUND: End-to-side anastomoses to connect the distal end of the great
      saphenous vein (GSV) to small target coronary arteries are commonly performed in
      sequential coronary artery bypass grafting (CABG). However, the oversize diameter
      ratio between the GSV and small target vessels at end-to-side anastomoses might
      induce adverse hemodynamic condition. The purpose of this study was to describe a
      distal end side-to-side anastomosis technique and retrospectively compare the
      effect of distal end side-to-side versus end-to-side anastomosis on graft flow
      characteristics. METHODS: We performed side-to-side anastomoses to connect the
      distal end of the GSV to small target vessels on 30 patients undergoing off-pump
      sequential CABG in our hospital between October 2012 and July 2013. Among the 30
      patients, end-to-side anastomoses at the distal end of the GSV were initially
      performed on 14 patients; however, due to poor graft flow, those anastomoses were
      revised into side-to-side anastomoses. We retrospectively compared the
      intraoperative graft flow characteristics of the end-to-side versus side-to-side
      anastomoses in the 14 patients. The patient outcomes were also evaluated.
      RESULTS: We found that the side-to-side anastomosis reconstruction improved
      intraoperative flow and reduced pulsatility index in all the 14 patients
      significantly. The 16 patients who had the distal end side-to-side anastomoses
      performed directly also exhibited satisfactory intraoperative graft flow. Three
      month postoperative outcomes for all the patients were satisfactory. CONCLUSIONS:
      Side-to-side anastomosis at the distal end of sequential vein grafts might be a
      promising strategy to connect small target coronary arteries to the GSV.

PMID- 24884775
TI  - Shaping the dynamic mitochondrial network.
AB  - In a majority of cell types, mitochondria form highly dynamic, tubular networks.
      Maintaining the shape of this complex network is critical for both mitochondrial
      and cellular function and involves the activities of mitochondrial division,
      fusion, motility, and tethering. Recent studies have advanced our understanding
      of the molecular mechanisms underlying these conserved activities and their
      integration with cellular needs. 

PMID- 24884778
TI  - Enhancement of gefitinib-induced growth inhibition by Marsdenia tenacissima
      extract in non-small cell lung cancer cells expressing wild or mutant EGFR.
AB  - BACKGROUND: Non-small cell lung cancer (NSCLC) expressed high levels of epidermal
      growth factor receptor (EGFR). Gefitinib (Iressa) has demonstrated clinical
      efficacy in NSCLC patients harboring EGFR mutations or refractory to
      chemotherapy. However, most of NSCLC patients are with wild type EGFR, and showed
      limited response to gefitinib. Therefore, to develop new effective therapeutic
      interventions for NSCLC is still required. Our previous study showed Marsdenia
      tenacissima extract (MTE) restored gefitinib efficacy in the resistant NSCLC
      cells, but whether MTE acts in the gefitinib-sensitive NSCLC cells is the same as
      it in the resistant one is unknown. METHODS: Dose response curves for gefitinib
      and MTE were generated for two sensitive NSCLC cell lines with mutant or wild
      type EGFR status. Three different sequential combinations of MTE and gefitinib on
      cell growth were evaluated using IC50 and Combination Index approaches. The flow
      cytometric method was used to detect cell apoptosis and cell cycle profile. The
      impact of MTE combined with gefitinib on cell molecular network response was
      studied by Western blotting. RESULTS: Unlike in the resistant NSCLC cells, our
      results revealed that low cytotoxic dose of MTE (8 mg/ml) combined gefitinib with
      three different schedules synergistically or additively enhanced the growth
      inhibition of gefitinib. Among which, MTE->MTE+gefitinib treatment was the most
      effective one. MTE markedly prompted cell cycle arrest and apoptosis caused by
      gefitinib both in EGFR mutant (HCC827) and wild type of NSCLC cells (H292). The
      Western blotting results showed that MTE->MTE+gefitinib treatment further
      enhanced the suppression of gefitinib on cell growth and apoptosis pathway such
      as ERK1/2 and PI3K/Akt/mTOR. This combination also blocked the activation of EGFR
      and c-Met which have cross-talk with each other. Unlike in gefitinib-resistant
      NSCLC cells, MTE alone also demonstrated certain unexpected modulation on EGFR
      related cell signal pathways in the sensitive cells. CONCLUSION: Our results
      suggest that MTE is a promising herbal medicine to improve gefitinib efficacy in
      NSCLC regardless of EGFR status. However, why MTE acted differently between
      gefitinib-sensitive and -resistant NSCLC cells needs a further research.

PMID- 24884779
TI  - Design of the INTEGRATE study: effectiveness and cost-effectiveness of a
      cardiometabolic risk assessment and treatment program integrated in primary care.
AB  - BACKGROUND: The increasing prevalence of cardiometabolic disease (CMD) in
      combination with an ageing population is a major public health problem. Early
      detection and management of individuals at risk for CMD is required to prevent
      future health problems with associated costs. General practice is the optimal
      health care setting to accomplish this goal. Prevention programs for
      identification and treatment of patients with an increased risk for CMD in
      primary care have been proven feasible. However, the effectiveness and cost
      effectiveness have yet to be demonstrated. The 'Personalized Prevention Approach
      for CardioMetabolic Risk' (PPA CMR) is such a prevention program. The objective
      of the INTEGRATE study is to investigate the effectiveness and cost-effectiveness
      of PPA CMR, as well as to establish determinants for participation and
      compliance. METHODS: The INTEGRATE study is designed as a stepped-wedge
      randomized controlled trial with a waiting list control group. In approximately
      40 general practices, all enlisted patients without CMD aged 45-70 years, are
      invited to participate in PPA CMR. After an online risk estimation, patients with
      a score above risk threshold are invited to the GP for additional measurements,
      detailed risk profiling and tailored treatment of risk factors through medication
      and/or lifestyle counseling. At baseline and after twelve months of follow-up
      lifestyle, health and work status of all participants are established with online
      questionnaires. Additionally after twelve months, we will determine health care
      utilization, costs of PPA CMR and compliance. Primary endpoints are the number of
      newly detected patients with CMD and changes in individual risk factors between
      the intervention and waiting list control group. Medical data will be extracted
      from the GPs' electronic medical records. In order to assess factors related to
      participation, we will send questionnaires to non-participants and assess
      characteristics of participating practices. For all participants, additional
      demographic characteristics will be available through Statistics Netherlands.
      DISCUSSION: The INTEGRATE study will provide insight into the effectiveness and
      cost-effectiveness of PPA CMR as well as determinants for participation and
      compliance, which represents essential information to guide further large-scale
      implementation of primary prevention programs for CMD. TRIAL REGISTRATION NUMBER:
      NTR4277, The Netherlands National Trial Register, 26-11-2013.

PMID- 24884780
TI  - Structure guided design and kinetic analysis of highly potent benzimidazole
      inhibitors targeting the PDEdelta prenyl binding site.
AB  - K-Ras is one of the most frequently mutated signal transducing human oncogenes.
      Ras signaling activity requires correct cellular localization of the GTPase. The
      spatial organization of K-Ras is controlled by the prenyl binding protein
      PDEdelta, which enhances Ras diffusion in the cytosol. Inhibition of the Ras
      PDEdelta interaction by small molecules impairs Ras localization and signaling.
      Here we describe in detail the identification and structure guided development of
      Ras-PDEdelta inhibitors targeting the farnesyl binding pocket of PDEdelta with
      nanomolar affinity. We report kinetic data that characterize the binding of the
      most potent small molecule ligands to PDEdelta and prove their binding to
      endogenous PDEdelta in cell lysates. The PDEdelta inhibitors provide promising
      starting points for the establishment of new drug discovery programs aimed at
      cancers harboring oncogenic K-Ras.

PMID- 24884781
TI  - Interleukin 32gamma (IL-32gamma) is highly expressed in cutaneous and mucosal
      lesions of American Tegumentary Leishmaniasis patients: association with tumor
      necrosis factor (TNF) and IL-10.
AB  - BACKGROUND: The interleukin 32 (IL-32) is a proinflammatory cytokine produced by
      immune and non-immune cells. It can be induced during bacterial and viral
      infections, but its production was never investigated in protozoan infections.
      American Tegumentary Leishmaniasis (ATL) is caused by Leishmania protozoan
      leading to cutaneous, nasal or oral lesions. The aim of this study was to
      evaluate the expression of IL-32 in cutaneous and mucosal lesions as well as in
      peripheral blood mononuclear cells (PBMC) exposed to Leishmania (Viannia)
      braziliensis. METHODS: IL-32, tumour necrosis factor (TNF) and IL-10 protein
      expression was evaluated by immunohistochemistry in cutaneous, mucosal lesions
      and compared to healthy specimens. The isoforms of IL-32alpha, beta, delta, gamma
      mRNA, TNF mRNA and IL-10 mRNA were assessed by qPCR in tissue biopsies of lesions
      and healthy skin and mucosa. In addition, PBMC from healthy donors were cultured
      with amastigotes of L. (V.) braziliensis. In lesions, the parasite subgenus was
      identified by PCR-RFLP. RESULTS: We showed that the mRNA expression of IL-32, in
      particular IL-32gamma was similarly up-regulated in lesions of cutaneous (CL) or
      mucosal (ML) leishmaniasis patients. IL-32 protein was produced by epithelial,
      endothelial, mononuclear cells and giant cells. The IL-32 protein expression was
      associated with TNF in ML but not in CL. IL-32 was not associated with IL-10 in
      both CL and ML. Expression of TNF mRNA was higher in ML than in CL lesions,
      however levels of IL-10 mRNA were similar in both clinical forms. In all lesions
      in which the parasite was detected, L. (Viannia) subgenus was identified.
      Interestingly, L. (V.) braziliensis induced only IL-32gamma mRNA expression in
      PBMC from healthy individuals. CONCLUSIONS: These data suggest that IL-32 plays a
      major role in the inflammatory process caused by L. (Viannia) sp or that IL-32 is
      crucial for controlling the L. (Viannia) sp infection.

PMID- 24884782
TI  - European Adrenal Insufficiency Registry (EU-AIR): a comparative observational
      study of glucocorticoid replacement therapy.
AB  - BACKGROUND: Increased morbidity and mortality associated with conventional
      glucocorticoid replacement therapy for primary adrenal insufficiency (primary AI;
      estimated prevalence 93-140/million), secondary AI (estimated prevalence, 150
      280/million, respectively) or congenital adrenal hyperplasia (estimated
      prevalence, approximately 65/million) may be due to the inability of typical
      glucocorticoid treatment regimens to reproduce the normal circadian profile of
      plasma cortisol. A once-daily modified-release formulation of hydrocortisone has
      been developed to provide a plasma cortisol profile that better mimics the
      daytime endogenous profile of cortisol. Here, we describe the protocol for the
      European Adrenal Insufficiency Registry (EU-AIR), an observational study to
      assess the long-term safety of modified-release hydrocortisone compared with
      conventional glucocorticoid replacement therapies in routine clinical practice
      (ClinicalTrials.gov identifier: NCT01661387). METHODS: Patients enrolled in EU
      AIR have primary or secondary AI and are receiving either modified-release or
      conventional glucocorticoid replacement therapy. The primary endpoints of EU-AIR
      are the incidence of intercurrent illness, adrenal crisis and serious adverse
      events (SAEs), as well as the duration of SAEs and dose changes related to SAEs.
      Data relating to morbidity, mortality, adverse drug reactions, dosing and
      concomitant therapies will be collected. Patient diaries will record illness
      related dose changes between visits. All decisions concerning medical care are
      made by the registry physician and patient. Enrolment is targeted at achieving
      3600 patient-years of treatment (1800 patient-years per group) for the primary
      analysis, which is focused on determining the non-inferiority of once-daily
      modified-release replacement therapy compared with conventional glucocorticoid
      therapy. RESULTS: Recruitment began in August 2012 and, as of March 2014, 801
      patients have been enrolled. Fifteen centres are participating in Germany, the UK
      and Sweden, with recruitment soon to be initiated in the Netherlands.
      CONCLUSIONS: EU-AIR will provide a unique opportunity not only to collect long
      term safety data on a modified-release preparation of glucocorticoid but also to
      evaluate baseline data on conventional glucocorticoid replacement. Such data
      should help to improve the treatment of AI.

PMID- 24884784
TI  - Protocol for disseminating an evidence-based fall prevention program in community
      senior centers: evaluation of translatability and public health impact via a
      single group pre-post study.
AB  - BACKGROUND: Falls are the leading cause of injury death in older adults and
      present a significant public health problem and a major burden to healthcare.
      Although there is sufficient evidence from randomized controlled trials to
      indicate that exercise can prevent falls in older people, few effective, evidence
      based fall prevention programs exist in community practice. Thus, there is a
      pressing need to translate and disseminate evidence-based exercise programs to
      community providers that serve older adults at increased risk of falling. The
      current study addresses this public health need by disseminating the evidence
      based Tai Ji Quan: Moving for Better Balance (TJQMBB) program through community
      senior centers. METHODS/DESIGN: The study uses a single-group design in which the
      TJQMBB program is being delivered to community-dwelling older adults through
      collaboration with senior centers in selected counties in Oregon, USA, for 48
      weeks, followed by a 24-week post-intervention follow-up. Study process and
      outcome measures will be evaluated in accordance with the components of the RE
      AIM framework that focus on Reach, Effectiveness, Adoption, Implementation and
      Maintenance. DISCUSSION: This study will determine whether the evidence-based
      TJQMBB fall prevention program can be disseminated through a broad spectrum of
      community-based senior centers that often cater to low-income, underserved
      community-dwelling older adults at risk of falling. If shown to be both
      practically implementable and sustainable, the TJQMBB program will provide an
      effective, potentially low-cost, easy-to-implement intervention that could be
      used by public health practitioners and community-based organizations to address
      the problem of falls among older adults. TRIAL REGISTRATION: ClinicalTrials.gov
      Identifier: NCT01854931.

PMID- 24884783
TI  - Differential binding of neutralizing and non-neutralizing antibodies to native
      like soluble HIV-1 Env trimers, uncleaved Env proteins, and monomeric subunits.
AB  - BACKGROUND: The trimeric envelope glycoproteins (Env) on the surface of HIV-1
      virions are the targets for neutralizing antibodies (NAbs). No candidate HIV-1
      immunogen has yet induced potent, broadly active NAbs (bNAbs). Part of the
      explanation may be that previously tested Env proteins inadequately mimic the
      functional, native Env complex. Trimerization and the proteolytic processing of
      Env precursors into gp120 and gp41 profoundly alter antigenicity, but soluble
      cleaved trimers are too unstable to serve as immunogens. By introducing
      stabilizing mutations (SOSIP), we constructed soluble, cleaved Env trimers
      derived from the HIV-1 subtype A isolate BG505 that resemble native Env spikes on
      virions both structurally and antigenically. RESULTS: We used surface plasmon
      resonance (SPR) to quantify antibody binding to different forms of BG505 Env: the
      proteolytically cleaved SOSIP.664 trimers, cleaved gp120-gp41ECTO protomers, and
      gp120 monomers. Non-NAbs to the CD4-binding site bound only marginally to the
      trimers but equally well to gp120-gp41ECTO protomers and gp120 monomers, whereas
      the bNAb VRC01, directed to the CD4bs, bound to all three forms. In contrast,
      bNAbs to V1V2 glycan-dependent epitopes bound preferentially (PG9 and PG16) or
      exclusively (PGT145) to trimers. We also explored the antigenic consequences of
      three different features of SOSIP.664 gp140 trimers: the engineered inter-subunit
      disulfide bond, the trimer-stabilizing I559P change in gp41ECTO, and proteolytic
      cleavage at the gp120-gp41ECTO junction. Each of these three features
      incrementally promoted native-like trimer antigenicity. We compared Fab and IgG
      versions of bNAbs and validated a bivalent model of IgG binding. The NAbs showed
      widely divergent binding kinetics and degrees of binding to native-like BG505
      SOSIP.664. High off-rate constants and low stoichiometric estimates of NAb
      binding were associated with large amounts of residual infectivity after NAb
      neutralization of the corresponding BG505.T332N pseudovirus. CONCLUSIONS: The
      antigenicity and structural integrity of cleaved BG505 SOSIP.664 trimers render
      these proteins good mimics of functional Env spikes on virions. In contrast,
      uncleaved gp140s antigenically resemble individual gp120-gp41ECTO protomers and
      gp120 monomers, but not native trimers. Although NAb binding to functional
      trimers may thus be both necessary and sufficient for neutralization, the
      kinetics and stoichiometry of the interaction influence the neutralizing efficacy
      of individual NAbs.

PMID- 24884785
TI  - Implications of differences in expression of sarcosine metabolism-related
      proteins according to the molecular subtype of breast cancer.
AB  - BACKGROUND: The goal of this study was to investigate the expression of sarcosine
      metabolism-related proteins, namely glycine N-methyltransferase (GNMT), sarcosine
      dehydrogenase (SARDH), and l-pipecolic acid oxidase (PIPOX), in the different
      breast cancer subtypes and to assess the implications of differences in
      expression pattern according to subtype. METHODS: We analyzed the expression of
      GNMT, SARDH, and PIPOX in a tissue microarray of 721 breast cancer cases using
      immunohistochemistry (IHC). We classified breast cancer cases into subtype
      luminal A, luminal B, HER-2, and triple negative breast cancer (TNBC) according
      to the status for the estrogen receptor (ER), progesterone receptor (PR), HER-2,
      and Ki-67. Sarcosine metabolism phenotype was stratified according to IHC results
      for GNMT, SARDH, and PIPOX: GNMT(+), SARDH and PIPOX(-) was classified as high
      sarcosine type; GNMT(-), SARDH or PIPOX(-) as low sarcosine type; GNMT(+), SARDH
      or PIPOX(+) as intermediate sarcosine type, and GNMT(-), SARDH and PIPOX(-) as
      null type. RESULTS: Expression of sarcosine metabolism-related proteins differed
      significantly according to breast cancer subtype (GNMT, p=0.005; SARDH, p=0.012;
      tumoral PIPOX, p=0.008; stromal PIPOX, p<0.001). These proteins were the most
      frequently expressed in HER-2 type tumors and the least in TNBC. Sarcosine
      metabolism phenotype also varied according to breast cancer subtype, with high
      sarcosine type the most common in HER-2, and null type the most common in TNBC
      (p=0.003). Univariate analysis revealed that GNMT expression (p=0.042), tumoral
      PIPOX negativity (p=0.039), and high sarcosine type (p=0.021) were associated
      with shorter disease-free survival (DFS). Multivariate analysis also revealed
      GNMT expression was an independent factor for shorter DFS (hazard ratio: 2.408,
      95% CI: 1.154-5.024, p=0.019). CONCLUSION: Expressions of sarcosine metabolism
      related proteins varied according to subtype of breast cancer, with HER-2 type
      tumors showing elevated expression of these proteins, and TNBC subtype showing
      decreased expression of these proteins. Expression of sarcosine metabolism
      related proteins was also associated with breast cancer prognosis.

PMID- 24884786
TI  - Mass distribution of free insecticide-treated nets do not interfere with
      continuous net distribution in Tanzania.
AB  - BACKGROUND: To protect the most vulnerable groups from malaria (pregnant women
      and infants) the Tanzanian Government introduced a subsidy (voucher) scheme in
      2004, on the basis of a public-private partnership. These vouchers are provided
      to pregnant women at their first antenatal care visit and mothers of infants at
      first vaccination. The vouchers are redeemed at registered retailers for a long
      lasting insecticidal net against the payment of a modest top-up price. The
      present work analysed a large body of data from the Tanzanian National Voucher
      Scheme, focusing on interactions with concurrent mass distribution campaigns of
      free nets. METHODS: In an ecologic study involving all regions of Tanzania,
      voucher redemption data for the period 2007-2011, as well as data on potential
      determinants of voucher redemption were analysed. The four outcome variables
      were: pregnant woman and infant voucher redemption rates, use of treated bed nets
      by all household members and by under- five children. Each of the outcomes was
      regressed with selected determinants, using a generalized estimating equation
      model and accounting for regional data clustering. RESULTS: There was a
      consistent improvement in voucher redemption rates over the selected time period,
      with rates >80% in 2011. The major determinants of redemption rates were the top
      up price paid by the voucher beneficiary, the retailer- clinic ratio, and socio
      economic status. Improved redemption rates after 2009 were most likely due to
      reduced top-up prices (following a change in policy). Redemption rates were not
      affected by two major free net distribution campaigns. During this period, there
      was a consistent improvement in net use across all the regions, with rates of up
      to 75% in 2011. CONCLUSION: The key components of the National Treated Nets
      Programme (NATNETS) seem to work harmoniously, leading to a high level of net use
      in the entire population. This calls for the continuation of this effort in
      Tanzania and for emulation by other countries with endemic malaria.

PMID- 24884787
TI  - A pilot three-month sitagliptin treatment increases serum adiponectin level in
      Japanese patients with type 2 diabetes mellitus--a randomized controlled trial
      START-J study.
AB  - BACKGROUND: The dipeptidyl-peptidase-IV (DPP-4) inhibitors, including
      sitagliptin, are used for the treatment of type 2 diabetes mellitus (T2DM).
      Adiponectin, an adipocyte-derived circulating protein, has anti-atherosclerotic
      and anti-diabetic properties and is effectively elevated in bloodstream by
      thiazolidinediones, an insulin sensitizer. However, the effect of sitagliptin
      treatment on serum adiponectin level in T2DM has not fully elucidated in Japanese
      T2DM patients. The aim of the present study was to examine the effect of
      sitagliptin treatment on serum adiponectin levels in T2DM subjects. METHODS:
      Twenty-six consecutive Japanese T2DM outpatients were recruited between April
      2011 and March 2013, and randomized into the control (conventional treatment, n =
      10) group and sitagliptin treatment group (n = 16). Serum adiponectin was
      measured by enzyme-linked immunosorbent assay. RESULTS: Indices of glycemic
      control, such as hemoglobin A1c, glycated albumin, and 1.5-anhydro-D-glucitol,
      were significantly improved after the three-month treatment in both the control
      and sitagliptin groups. Serum adiponectin level was significantly increased in
      sitagliptin group from 6.7 +/- 0.8 to 7.4 +/- 1.0 MUg/mL without change of body
      mass index (p = 0.034), while serum adiponectin level was not altered in the
      control group (p = 0.601). CONCLUSION: In Japanese T2DM patients, serum
      adiponectin level was elevated by three-month treatment with sitagliptin without
      change of body weight. TRIAL REGISTRATION: UMIN000004721.

PMID- 24884788
TI  - Gaps in universal health coverage in Malawi: a qualitative study in rural
      communities.
AB  - BACKGROUND: In sub-Saharan Africa, universal health coverage (UHC) reforms have
      often adopted a technocratic top-down approach, with little attention being paid
      to the rural communities' perspective in identifying context specific gaps to
      inform the design of such reforms. This approach might shape reforms that are not
      sufficiently responsive to local needs. Our study explored how rural communities
      experience and define gaps in universal health coverage in Malawi, a country
      which endorses free access to an Essential Health Package (EHP) as a means
      towards universal health coverage. METHODS: We conducted a qualitative cross
      sectional study in six rural communities in Malawi. Data was collected from 12
      Focus Group Discussions with community residents and triangulated with 8 key
      informant interviews with health care providers. All respondents were selected
      through stratified purposive sampling. The material was tape-recorded, fully
      transcribed, and coded by three independent researchers. RESULTS: The results
      showed that the EHP has created a universal sense of entitlements to free health
      care at the point of use. However, respondents reported uneven distribution of
      health facilities and poor implementation of public-private service level
      agreements, which have led to geographical inequities in population coverage and
      financial protection. Most respondents reported affordability of medical costs at
      private facilities and transport costs as the main barriers to universal
      financial protection. From the perspective of rural Malawians, gaps in financial
      protection are mainly triggered by supply-side access-related barriers in the
      public health sector such as: shortages of medicines, emergency services,
      shortage of health personnel and facilities, poor health workers' attitudes,
      distance and transportation difficulties, and perceived poor quality of health
      services. CONCLUSIONS: Moving towards UHC in Malawi, therefore, implies the
      introduction of appropriate interventions to fill the financial protection gaps
      in the private sector and the access-related gaps in the public sector and/or an
      effective public-private partnership that completely integrates both sectors.
      Current universal health coverage reforms need to address context specific gaps
      and be carefully crafted to avoid creating a sense of universal entitlements in
      principle, which may not be effectively received by beneficiaries due to
      contextual and operational bottlenecks.

PMID- 24884789
TI  - Patterns of nutrients' intake at six months in the northeast of Italy: a cohort
      study.
AB  - BACKGROUND: Adequate complementary feeding is recognized as an important
      predictor of health later in life. The objective of this study was to describe
      the feeding practices and nutrients' intake, and their association with
      breastfeeding at six months of age, in a cohort of infants enrolled at birth in
      the maternity hospital of Trieste, Italy. METHODS: Out of 400 infants enrolled at
      birth, 268 (67%) had complete data gathered through a 24-hour feeding diary on
      three separate days at six months, and two questionnaires administered at birth
      and at six months. Data from feeding diaries were used to estimate nutrients'
      intakes using the Italian food composition database included in the software. To
      estimate the quantity of breastmilk, information was gathered on the frequency
      and length of breastfeeds. RESULTS: At six months, 70% of infants were breastfed
      and 94% were given complementary foods. The average daily caloric intake was
      higher in non-breastfed (723 Kcal) than in breastfed infants (547 Kcal, p <
      0.001) due to energy provided by complementary foods (321 vs. 190 Kcal, p <
      0.001) and milk (363 vs. 301 Kcal, p = 0.007). Non-breastfed infants had also
      higher intakes of carbohydrates, proteins, and fats. The mean intake of
      macronutrients was within recommended ranges in both groups, except for the
      higher protein intake in non-breastfed infants. These consumed significantly
      higher quantities of commercial baby foods than breastfed infants. CONCLUSIONS:
      Contrary to what is recommended, 94% of infants were not exclusively breastfed
      and were given complementary foods at six months. The proportion of daily energy
      intake from complementary foods was around 50% higher than recommended and with
      significant differences between breastfed and non-breastfed infants, with
      possible consequences for future nutrition and health.

PMID- 24884791
TI  - Does the amygdala response correlate with the personality trait 'harm avoidance'
      while evaluating emotional stimuli explicitly?
AB  - BACKGROUND: The affective personality trait 'harm avoidance' (HA) from
      Cloninger's psychobiological personality model determines how an individual deals
      with emotional stimuli. Emotional stimuli are processed by a neural network that
      include the left and right amygdalae as important key nodes. Explicit, implicit
      and passive processing of affective stimuli are known to activate the amygdalae
      differently reflecting differences in attention, level of detailed analysis of
      the stimuli and the cognitive control needed to perform the required task.
      Previous studies revealed that implicit processing or passive viewing of
      affective stimuli, induce a left amygdala response that correlates with HA. In
      this new study we have tried to extend these findings to the situation in which
      the subjects were required to explicitly process emotional stimuli. METHODS: A
      group of healthy female participants was asked to rate the valence of positive
      and negative stimuli while undergoing fMRI. Afterwards the neural responses of
      the participants to the positive and to the negative stimuli were separately
      correlated to their HA scores and compared between the low and high HA
      participants. RESULTS: Both analyses revealed increased neural activity in the
      left laterobasal (LB) amygdala of the high HA participants while they were rating
      the positive and the negative stimuli. CONCLUSIONS: Our results indicate that the
      left amygdala response to explicit processing of affective stimuli does correlate
      with HA.

PMID- 24884792
TI  - South Asian populations in Canada: migration and mental health.
AB  - BACKGROUND: South Asian populations are the largest visible minority group in
      Canada; however, there is very little information on the mental health of these
      populations. The objective of this study was to determine the prevalence rates
      and characteristics of mental health outcomes for South Asian first-generation
      immigrant and second-generation Canadian-born populations. METHODS: The Canadian
      Community Health Survey (CCHS) 2011 was used to calculate the estimated
      prevalence rates of the following mental health outcomes: mood disorders, anxiety
      disorders, fair-poor self-perceived mental health status, and extremely stressful
      life stress. The characteristics associated with these four mental health
      outcomes were determined through multivariate logistic regression analysis of
      merged CCHS 2007-2011 data. RESULTS: South Asian Canadian-born (3.5%, 95% CI 3.4
      3.6%) and South Asian immigrant populations (3.5%, 95% CI 3.5-3.5%) did not vary
      significantly in estimated prevalence rates of mood disorders. However, South
      Asian immigrants experienced higher estimated prevalence rates of diagnosed
      anxiety disorders (3.4%, 95% CI 3.4-3.5 vs. 1.1%, 95% CI 1.1-1.1%) and self
      reported extremely stressful life stress (2.6%, 95% CI 2.6-2.7% vs. 2.4%, 95% CI
      2.3-2.4%) compared to their Canadian-born counterparts. Lastly, South Asian
      Canadian-born populations had a higher estimated prevalence rate of poor-fair
      self-perceived mental health status (4.4%, 95% CI 4.3-4.5%) compared to their
      immigrant counterparts (3.4%, 95% CI 3.3-3.4%). Different profiles of mental
      health determinants emerged for South Asian Canadian-born and immigrant
      populations. Female gender, having no children under the age of 12 in the
      household, food insecurity, poor-fair self-rated health status, being a current
      smoker, immigrating to Canada before adulthood, and taking the CCHS survey in
      either English or French was associated with greater risk of negative mental
      health outcomes for South Asian immigrant populations, while not being currently
      employed, having a regular medical doctor, and inactive physical activity level
      were associated with greater risk for South Asian Canadian-born populations.
      CONCLUSIONS: Mental health outreach programs need to be cognizant of the
      differences in prevalence rates and characteristics of mental health outcomes for
      South Asian immigrant and Canadian-born populations to better tailor mental
      health services to be responsive to the unique mental health needs of South Asian
      populations in Canada.

PMID- 24884790
TI  - Inference of high resolution HLA types using genome-wide RNA or DNA sequencing
      reads.
AB  - BACKGROUND: Accurate HLA typing at amino acid level (four-digit resolution) is
      critical in hematopoietic and organ transplantations, pathogenesis studies of
      autoimmune and infectious diseases, as well as the development of immunoncology
      therapies. With the rapid adoption of genome-wide sequencing in biomedical
      research, HLA typing based on transcriptome and whole exome/genome sequencing
      data becomes increasingly attractive due to its high throughput and convenience.
      However, unlike targeted amplicon sequencing, genome-wide sequencing often
      employs a reduced read length and coverage that impose great challenges in
      resolving the highly homologous HLA alleles. Though several algorithms exist and
      have been applied to four-digit typing, some deliver low to moderate accuracies,
      some output ambiguous predictions. Moreover, few methods suit diverse read
      lengths and depths, and both RNA and DNA sequencing inputs. New algorithms are
      therefore needed to leverage the accuracy and flexibility of HLA typing at high
      resolution using genome-wide sequencing data. RESULTS: We have developed a new
      algorithm named PHLAT to discover the most probable pair of HLA alleles at four
      digit resolution or higher, via a unique integration of a candidate allele
      selection and a likelihood scoring. Over a comprehensive set of benchmarking data
      (a total of 768 HLA alleles) from both RNA and DNA sequencing and with a broad
      range of read lengths and coverage, PHLAT consistently achieves a high accuracy
      at four-digit (92%-95%) and two-digit resolutions (96%-99%), outcompeting most of
      the existing methods. It also supports targeted amplicon sequencing data from
      Illumina Miseq. CONCLUSIONS: PHLAT significantly leverages the accuracy and
      flexibility of high resolution HLA typing based on genome-wide sequencing data.
      It may benefit both basic and applied research in immunology and related fields
      as well as numerous clinical applications.

PMID- 24884793
TI  - Postoperative complications do not influence the pattern of early lung function
      recovery after lung resection for lung cancer in patients at risk.
AB  - BACKGROUND: The pattern and factors influencing the lung function recovery in the
      first postoperative days are still not fully elucidated, especially in patients
      at increased risk. METHODS: Prospective study on 60 patients at increased risk,
      who underwent a lung resection for primary lung cancer. INCLUSION CRITERIA:
      complete resection and one or more known risk factors in form of COPD,
      cardiovascular disorders, advanced age or other comorbidities. Previous
      myocardial infarction, myocardial revascularization or stenting, cardiac rhythm
      disorders, arterial hypertension and myocardiopathy determined the increased
      cardiac risk. The severity of COPD was graded according to GOLD criteria. The
      trend of the postoperative lung function recovery was assessed by performing
      spirometry with a portable spirometer. RESULTS: Cardiac comorbidity existed in
      55%, mild and moderate COPD in 20% and 35% of patients respectively. Measured
      values of FVC% and FEV1% on postoperative days one, three and seven, showed
      continuous improvement, with significant difference between the days of
      measurement, especially between days three and seven. There was no difference in
      the trend of the lung function recovery between patients with and without
      postoperative complications. Whilst pO2 was decreasing during the first three
      days in a roughly parallel fashion in patients with respiratory, surgical
      complications and in patients without complications, a slight hypercapnia
      registered on the first postoperative day was gradually abolished in all groups
      except in patients with cardiac complications. CONCLUSION: Extent of the lung
      resection and postoperative complications do not significantly influence the
      trend of the lung function recovery after lung resection for lung cancer.

PMID- 24884794
TI  - Glycosylated hemoglobin A1c as a marker predicting the severity of coronary
      artery disease and early outcome in patients with stable angina.
AB  - BACKGROUND: Glycosylated hemoglobin A1C (HbA1c) has been widely recognized as a
      marker for predicting the severity of diabetes mellitus (DM) and several
      cardiovascular diseases. However, whether HbA1c could predict the severity and
      clinical outcomes in patients with stable coronary artery disease (CAD) remains
      largely unknown. We determine relationship of HbA1c with severity and outcome in
      patients with stable CAD. METHODS: We enrolled 1433 patients with stable angina
      who underwent coronary angiography and were followed up for an average 12 months.
      The patients were classified into three groups by tertiles of baseline HbA1c
      level (low group <5.7%, n = 483; intermediate group 5.7 - 6.3%, n = 512; high
      group >6.3%, n = 438). The relationships between the plasma HbA1c and severity of
      CAD and early clinical outcomes were evaluated. RESULTS: High HbA1c was
      associated with three-vessel disease. Area under the receivers operating
      characteristic curve (AUC = 0.67, 95% CI: 0.63-0.71, P < 0.001) and multivariate
      logistic regression analysis suggested that HbA1C was an independent predictor of
      severity of CAD (OR = 1.60, 95% CI: 1.29-1.99, P < 0.001) even after adjusting
      for gender, age, risk factor of CAD, lipid profile and fasting blood glucose.
      During follow-up, 133 patients underwent pre-specified outcomes. After adjusting
      for multiple variables in the Cox regression model, HbA1C remained to be an
      independent predictor of poor prognosis (HR = 1.28, 95% CI: 1.12-1.45, P <
      0.001). CONCLUSIONS: We concluded that high level of baseline HbA1c appeared to
      be an independent predictor for the severity of CAD and poor outcome in patients
      with stable CAD.

PMID- 24884795
TI  - The polyene antifungals, amphotericin B and nystatin, cause cell death in
      Saccharomyces cerevisiae by a distinct mechanism to amphibian-derived
      antimicrobial peptides.
AB  - BACKGROUND: There is a pressing need to identify novel antifungal drug targets to
      aid in the therapy of life-threatening mycoses and overcome increasing drug
      resistance. Identifying specific mechanisms of action of membrane-interacting
      antimicrobial drugs on the model fungus Saccharomyces cerevisiae is one avenue
      towards addressing this issue. The S. cerevisiae deletion mutants Deltaizh2,
      Deltaizh3, Deltaaif1 and Deltastm1 were demonstrated to be resistant to amphibian
      derived antimicrobial peptides (AMPs). The purpose of this study was to examine
      whether AMPs and polyene antifungals have a similar mode of action; this was done
      by comparing the relative tolerance of the mutants listed above to both classes
      of antifungal. FINDINGS: In support of previous findings on solid media it was
      shown that Deltaizh2 and Deltaizh3 mutants had increased resistance to both
      amphotericin B (1-2 MUg ml-1) and nystatin (2.5 - 5 MUg ml-1) in liquid culture,
      after acute exposure. However, Deltaaif1 and Deltastm1 had wild-type levels of
      susceptibility to these polyenes. The generation of reactive oxygen species (ROS)
      after exposure to amphotericin B was also reduced in Deltaizh2 and Deltaizh3.
      These data indicated that polyene antifungal and AMPs may act via distinct
      mechanisms of inducing cell death in S. cerevisiae. CONCLUSIONS: Further
      understanding of the mechanism(s) involved in causing cell death and the roles of
      IZH2 and IZH3 in drug susceptibility may help to inform improved drug design and
      treatment of fungal pathogens.

PMID- 24884796
TI  - Gluteal silicone injections and total hip arthroplasty: a case report.
AB  - INTRODUCTION: Silicone injection is a common procedure in cosmetic surgery.
      Granuloma formation and migration are the most commonly observed complications.
      CASE PRESENTATION: We report an unusual case of avascular necrosis of the hip in
      a 41-year-old woman from Thailand presenting with hip pain. Subcutaneous nodules
      were observed in the clinical examination. A pelvic X-ray revealed necrosis of
      the right femoral head and histological analysis of the punctuated nodules showed
      a reaction of foreign body granulomas. During surgical treatment with a hip
      replacement solitary silicone cysts were removed. CONCLUSIONS: This case report
      emphasizes that orthopedic surgeons treating patients with necrosis of the hip
      joint in combination with palpable granulomas in the gluteal region have to be
      aware of silicone augmentation and its potential complications before planning a
      hip replacement.

PMID- 24884797
TI  - Exploration of population and practice characteristics explaining differences
      between practices in the proportion of hospital admissions that are emergencies.
AB  - BACKGROUND: Emergency (unscheduled) and elective (scheduled) use of secondary
      care varies between practices. Past studies have described factors associated
      with the number of emergency admissions; however, high quality care of chronic
      conditions, which might include increased specialist referrals, could be followed
      by reduced unscheduled care. We sought to characterise practices according to the
      proportion of total hospital admissions that were emergency admissions, and
      identify predictors of this proportion. METHOD: The study included 229 general
      practices in Leicestershire, Northamptonshire and Rutland, England. Publicly
      available data were obtained on scheduled and unscheduled secondary care usage,
      and on practice and patient characteristics: age; gender; list size; observed
      prevalence, expected prevalence and the prevalence gap of coronary heart disease,
      hypertension and stroke; deprivation; headcount number of GPs per 1000 patients;
      total and clinical quality and outcomes framework (QOF) scores; ethnicity;
      proportion of patients seen within two days by a GP; proportion able to see their
      preferred GP. Using the proportion of admissions that were emergency admissions,
      seven categories of practices were created, and a regression analysis was
      undertaken to identify predictors of the proportion. RESULTS: In univariate
      analysis, practices with higher proportions of admissions that were emergencies
      tended to have fewer older patients, higher proportions of male patients, fewer
      white patients, greater levels of deprivation, smaller list sizes, lower recorded
      prevalence of coronary heart disease and stroke, a bigger gap between the
      expected and recorded levels of stroke, and lower proportions of total and
      clinical QOF points achieved. In the multivariate regression, higher deprivation,
      fewer white patients, more male patients, lower recorded prevalence of
      hypertension, more outpatient appointments, and smaller practice list size were
      associated with higher proportions of total admissions being emergencies.
      CONCLUSION: In monitoring use of secondary care services, the role of population
      characteristics in determining levels of use is important, but so too is the
      ability of practices to meet the demands for care that face them. The level of
      resources, and the way in which available resources are used, are likely to be
      key in determining whether a practice is able to meet the health care needs of
      its patients.

PMID- 24884798
TI  - Change in Oral Impacts on Daily Performances (OIDP) with increasing age: testing
      the evaluative properties of the OIDP frequency inventory using prospective data
      from Norway and Sweden.
AB  - BACKGROUND: Oral health-related quality of life, OHRQoL, among elderly is an
      important concern for the health and welfare policy in Norway and Sweden. The aim
      of the study was to assess reproducibility, longitudinal validity and
      responsiveness of the OIDP frequency score. Whether the temporal relationship
      between tooth loss and OIDP varied by country of residence was also investigated.
      METHODS: In 2007 and 2012, all inhabitants born in 1942 in three and two counties
      of Norway and Sweden were invited to participate in a self-administered
      questionnaire survey. In Norway the response rates were 58.0% (4211/7248) and
      54.5% (3733/6841) in 2007 and 2012. Corresponding figures in Sweden were 73.1%
      (6078/8313) and 72.2% (5697/7889), respectively. RESULTS: Reproducibility of the
      OIDP in terms of intra-class correlation coefficient (ICC) was 0.73 in Norway and
      0.77 in Sweden. The mean change scores for OIDP were predominantly negative among
      those who worsened, zero in those who did not change and positive in participants
      who improved change scores of the reference variables; self-reported oral health
      and tooth loss. General Linear Models (GLM) repeated measures revealed
      significant interactions between OIDP and change scores of the reference
      variables (p < 0.05). Stratified analysis revealed that the mean OIDP frequency
      score worsened in participants who became dissatisfied- and improved in
      participants who became satisfied with oral health. Compared to participants who
      maintained all teeth, those who lost teeth were more likely to experience
      improvement and worsening of OIDP across both countries. The two-way interaction
      between country and tooth loss was not statistically significant. CONCLUSIONS:
      Changes in OIDP at the individual level were more pronounced than the percentage
      distribution of OIDP at each point in time would suggest. The OIDP frequency
      score showed promising evaluative properties in terms of acceptable longitudinal
      validity, responsiveness and reproducibility among older people in Norway and
      Sweden. This suggests that the OIDP instrument is able to detect change in the
      oral health status that occurred over the 5 year period investigated. Norwegian
      elderly were more likely to report worsening in OIDP than their Swedish
      counterparts. Disease prevention should be at focus when formulating the health
      policy for older people.

PMID- 24884799
TI  - A transgenic approach to study argininosuccinate synthetase gene expression.
AB  - BACKGROUND: Argininosuccinate synthetase (ASS) participates in urea, nitric oxide
      and arginine production. Besides transcriptional regulation, a post
      transcriptional regulation affecting nuclear precursor RNA stability has been
      reported. To study whether such post-transcriptional regulation underlines
      particular temporal and spatial ASS expression, and to investigate how human ASS
      gene behaves in a mouse background, a transgenic mouse system using a modified
      bacterial artificial chromosome carrying the human ASS gene tagged with EGFP was
      employed. RESULTS: Two lines of ASS-EGFP transgenic mice were generated: one with
      EGFP under transcriptional control similar to that of the endogenous ASS gene,
      another with EGFP under both transcriptional and post-transcriptional regulation
      as that of the endogenous ASS mRNA. EGFP expression in the liver, the organ for
      urea production, and in the intestine and kidney that are responsible for
      arginine biosynthesis, was examined. Organs taken from embryos E14.5 stage to
      young adult were examined under a fluorescence microscope either directly or
      after cryosectioning. The levels of EGFP and endogenous mouse Ass mRNAs were also
      quantified by S1 nuclease mapping. EGFP fluorescence and EGFP mRNA levels in both
      the liver and kidney were found to increase progressively from embryonic stage
      toward birth. In contrast, EGFP expression in the intestine was higher in
      neonates and started to decline at about 3 weeks after birth. Comparison between
      the EGFP profiles of the two transgenic lines indicated the developmental and
      tissue-specific regulation was mainly controlled at the transcriptional level.
      The ASS transgene was of human origin. EGFP expression in the liver followed
      essentially the mouse Ass pattern as evidenced by zonation distribution of
      fluorescence and the level of EGFP mRNA at birth. However, in the small
      intestine, Ass mRNA level declined sharply at 3 week of age, and yet substantial
      EGFP mRNA was still detectable at this stage. Thus, the time course of EGFP
      expression in the transgenic mice resembled that of the human ASS gene.
      CONCLUSIONS: We demonstrate that the transgenic mouse system reported here has
      the merit of sensitivity and direct visualization advantage, and is ideal for
      annotating temporal and spatial expression profiles and the regulation mode of
      the ASS gene.

PMID- 24884800
TI  - Measuring changes in perception using the Student Perceptions of Physician
      Pharmacist Interprofessional Clinical Education (SPICE) instrument.
AB  - BACKGROUND: The Student Perceptions of Physician-Pharmacist Interprofessional
      Clinical Education (SPICE) instrument contains 10 items, 3 factors
      (interprofessional teamwork and team-based practice, roles/responsibilities for
      collaborative practice, and patient outcomes from collaborative practice), and
      utilizes a five-point response scale (1 = strongly disagree, 5 = strongly agree).
      Given the SPICE instrument's demonstrated validity and reliability, the objective
      of this study was to evaluate whether it was capable of measuring changes in
      medical (MS) and pharmacy students' (PS) perceptions following an
      interprofessional education (IPE) experience. METHODS: In this prospective cohort
      study, MS and PS completed the SPICE instrument before and after participation in
      a predefined IPE experience. Descriptive statistics were used to characterize
      students and pre-post responses. Independent samples t tests and Fisher's Exact
      tests were used to assess group difference in demographic variables. Mann Whitney
      U tests were used to assess between-group differences in item scores. Wilcoxon
      Signed-Rank tests were used to evaluate post-participation changes in item
      scores. Spearman correlations were calculated to assess associations between
      ordinal demographic variables and item scores, and whether the number of clinic
      visits completed was associated with post-test responses. Paired samples t tests
      were used to calculate mean score changes for each of the factors. RESULTS:
      Thirty-four MS and 15 PS were enroled. Baseline differences included age (25.3.
      +/- 1.3 MS vs. 28.7 +/- 4.4 PS; p = 0.013), years full-time employment (0.71 +/-
      0.97 MS vs. 4.60 +/- 4.55 PS; p < 0.001), and number of prior IPE rotations (1.41
      +/- 1.74 MS vs. 3.13 +/- 2.1 PS; p < 0.001). Two items generated baseline
      differences; 1 persisted post-participation: whether MS/PS should be involved in
      teamwork (3.91 MS vs. 4.60 PS; p < 0.001). For all students, significant mean
      score increases were observed for role clarity ("my role" [3.72 vs. 4.11; p =
      0.001] and "others' roles" [3.87 vs. 4.17; p = 0.001]), impact of teamwork on
      patient satisfaction (3.72 vs. 4.34; p < 0.001), and ideal curricular location
      for IPE (4.06 vs. 4.34; p = 0.002). Significant increases were observed for all
      three factors (teamwork, p = 0.003; roles/responsibilities and patient outcomes,
      p < 0.001). CONCLUSIONS: This study demonstrated the SPICE instrument's ability
      to measure changes in perception for medical and pharmacy students exposed to an
      IPE experience, both at the individual item level and at the factor level.

PMID- 24884801
TI  - Ophthalmic manifestation of disseminated cutaneous Mycobacterium avium
      intracellulare complex in a child with a presumed primary IL-12 receptor defect.

PMID- 24884802
TI  - Sociodemographic and behavioral factors associated with physical activity in
      Brazilian adolescents.
AB  - BACKGROUND: Physical activity in adolescents is associated with short- and long
      term health benefits. Physical activity can occur in various domains and is
      influenced by a complex network of factors. The aims of this study are 1) to
      describe the physical activity of Brazilian adolescents in physical education
      classes, during leisure time, and during active commuting and 2) to investigate
      the socio-demographic and behavioral factors associated with physical activity.
      METHODS: The representative sample included 109,104 Brazilian students in the
      final year of elementary school from 2,842 schools. The weekly frequency and
      duration of physical activity were assessed. A variety of socio-demographic and
      behavioral factors were studied. A multiple Poisson regression analysis was used
      to test for associations between physical activity and the socio-demographic and
      behavioral variables. RESULTS: Most of the students (97.0%) engaged in physical
      activity in at least one of the domains studied, especially physical education at
      school (81.7%) and leisure time physical activity (67.5%). However, only 29% of
      the adolescents reached the recommended level of physical activity. Among the
      adolescents who reached the minimum recommended time for physical activity, the
      various domains contributed the following proportions to total physical activity:
      leisure time physical activity (PR 12.5; 95% CI 11.17-13.97), active commuting
      (PR 1.63; 95% CI 1.59-1.67), and physical education at school (PR 1.36; 95% CI
      1.29-1.44). The weekly frequency of all activities was greater among boys than
      among girls. Moreover, nearly two-thirds (61.8%) of students spent more than two
      hours per day engaging in sedentary behaviors; the prevalence of sedentary
      behaviors was similar between boys and girls (59.0 and 64.5%, respectively).Total
      level of physical activity, leisure time physical activity, and active commuting
      were associated with higher nutritional scores. CONCLUSIONS: Physical activity is
      important in any health promotion program. Therefore, it is necessary to invest
      in policies and interagency initiatives that promote all domains and to ensure
      that the general population helps determine the scope and design of such
      policies.

PMID- 24884803
TI  - Discovery of transgene insertion sites by high throughput sequencing of mate pair
      libraries.
AB  - BACKGROUND: Transgenesis by random integration of a transgene into the genome of
      a zygote has become a reliable and powerful method for the creation of new mouse
      strains that express exogenous genes, including human disease genes, tissue
      specific reporter genes or genes that allow for tissue specific recombination.
      Nearly 6,500 transgenic alleles have been created by random integration in
      embryos over the last 30 years, but for the vast majority of these strains, the
      transgene insertion sites remain uncharacterized. RESULTS: To obtain a complete
      understanding of how insertion sites might contribute to phenotypic outcomes, to
      more cost effectively manage transgenic strains, and to fully understand
      mechanisms of instability in transgene expression, we've developed methodology
      and a scoring scheme for transgene insertion site discovery using high throughput
      sequencing data. CONCLUSIONS: Similar to other molecular approaches to transgene
      insertion site discovery, high-throughput sequencing of standard paired-end
      libraries is hindered by low signal to noise ratios. This problem is exacerbated
      when the transgene consists of sequences that are also present in the host
      genome. We've found that high throughput sequencing data from mate-pair libraries
      are more informative when compared to data from standard paired end libraries. We
      also show examples of the genomic regions that harbor transgenes, which have in
      common a preponderance of repetitive sequences.

PMID- 24884804
TI  - The role of high cell density in the promotion of neuroendocrine
      transdifferentiation of prostate cancer cells.
AB  - BACKGROUND: Tumor heterogeneity and the plasticity of cancer cells present
      challenges for effective clinical diagnosis and therapy. Such challenges are
      epitomized by neuroendocrine transdifferentiation (NED) and the emergence of
      neuroendocrine-like cancer cells in prostate tumors. This phenomenon frequently
      arises from androgen-depleted prostate adenocarcinoma and is associated with the
      development of castration-resistant prostate cancer and poor prognosis. RESULTS:
      In this study, we showed that NED was evoked in both androgen receptor (AR)
      positive and AR-negative prostate epithelial cell lines by growing the cells to a
      high density. Androgen depletion and high-density cultivation were both
      associated with cell cycle arrest and deregulated expression of several cell
      cycle regulators, such as p27Kip1, members of the cyclin D protein family, and
      Cdk2. Dual inhibition of Cdk1 and Cdk2 using pharmacological inhibitor or RNAi
      led to modulation of the cell cycle and promotion of NED. We further demonstrated
      that the cyclic adenosine 3', 5'-monophosphate (cAMP)-mediated pathway is
      activated in the high-density conditions. Importantly, inhibition of cAMP
      signaling using a specific inhibitor of adenylate cyclase, MDL-12330A, abolished
      the promotion of NED by high cell density. CONCLUSIONS: Taken together, our
      results imply a new relationship between cell cycle attenuation and promotion of
      NED and suggest high cell density as a trigger for cAMP signaling that can
      mediate reversible NED in prostate cancer cells.

PMID- 24884805
TI  - Differential expression of C-reactive protein and serum amyloid A in different
      cell types in the lung tissue of chronic obstructive pulmonary disease patients.
AB  - BACKGROUND: Chronic systemic inflammatory syndrome has been implicated in the
      pathobiology of extrapulmonary manifestations of chronic obstructive pulmonary
      disease (COPD). We aimed to investigate which cell types within lung tissue are
      responsible for expressing major acute-phase reactants in COPD patients and
      disease-free ("resistant") smokers. METHODS: An observational case-control study
      was performed to investigate three different cell types in surgical lung samples
      of COPD patients and resistant smokers via expression of the C-reactive protein
      (CRP) and serum amyloid A (SAA1, SAA2 and SAA4) genes. Epithelial cells,
      macrophages and fibroblasts from the lung parenchyma were separated by magnetic
      microbeads (CD326, CD14 and anti-fibroblast), and gene expression was evaluated
      by RT-PCR. RESULTS: The sample consisted of 74 subjects, including 40 COPD
      patients and 34 smokers without disease. All three cell types were capable of
      synthesizing these biomarkers to some extent. In fibroblasts, gene expression
      analysis of the studied biomarkers demonstrated increased SAA2 and decreased SAA1
      in patients with COPD. In epithelial cells, there was a marked increase in CRP,
      which was not observed in fibroblasts or macrophages. In macrophages, however,
      gene expression of these markers was decreased in COPD patients compared to
      controls. CONCLUSIONS: These results provide novel information regarding the gene
      expression of CRP and SAA in different cell types in the lung parenchyma. This
      study revealed differences in the expression of these markers according to cell
      type and disease status and contributes to the identification of cell types that
      are responsible for the secretion of these molecules.

PMID- 24884807
TI  - Effectiveness of the Chest Pain Choice decision aid in emergency department
      patients with low-risk chest pain: study protocol for a multicenter randomized
      trial.
AB  - BACKGROUND: Chest pain is the second most common reason patients visit emergency
      departments (EDs) and often results in very low-risk patients being admitted for
      prolonged observation and advanced cardiac testing. Shared decision-making,
      including educating patients regarding their 45-day risk for acute coronary
      syndrome (ACS) and management options, might safely decrease healthcare
      utilization. METHODS/DESIGN: This is a protocol for a multicenter practical
      patient-level randomized trial to compare an intervention group receiving a
      decision aid, Chest Pain Choice (CPC), to a control group receiving usual care.
      Adults presenting to five geographically and ethnically diverse EDs who are being
      considered for admission for observation and advanced cardiac testing will be
      eligible for enrollment. We will measure the effect of CPC on (1) patient
      knowledge regarding their 45-day risk for ACS and the available management
      options (primary outcome); (2) patient engagement in the decision-making process;
      (3) the degree of conflict patients experience related to feeling uninformed
      (decisional conflict); (4) patient and clinician satisfaction with the decision
      made; (5) the rate of major adverse cardiac events at 30 days; (6) the proportion
      of patients admitted for advanced cardiac testing; and (7) healthcare
      utilization. To assess these outcomes, we will administer patient and clinician
      surveys immediately after each clinical encounter, obtain video recordings of the
      patient-clinician discussion, administer a patient healthcare utilization diary,
      analyze hospital billing records, review the electronic medical record, and
      conduct telephone follow-up. DISCUSSION: This multicenter trial will robustly
      assess the effectiveness of a decision aid on patient-centered outcomes, safety,
      and healthcare utilization in low-risk chest pain patients from a variety of
      geographically and ethnically diverse EDs. TRIAL REGISTRATION: NCT01969240.

PMID- 24884806
TI  - Sodium iodide symporter (NIS) in extrathyroidal malignancies: focus on breast and
      urological cancer.
AB  - BACKGROUND: Expression and function of sodium iodide symporter (NIS) is requisite
      for efficient iodide transport in thyrocytes, and its presence in cancer cells
      allows the use of radioiodine as a diagnostic and therapeutic tool in thyroid
      neoplasia. Discovery of NIS expression in extrathyroidal tissues, including
      transformed cells, has opened a novel field of research regarding NIS-expressing
      extrathyroidal neoplasia. Indeed, expression of NIS may be used as a biomarker
      for diagnostic, prognostic, and therapeutic purposes. Moreover, stimulation of
      endogenous NIS expression may permit the radioiodine treatment of extrathyroidal
      lesions by concentrating this radioisotope. RESULTS: This review describes recent
      findings in NIS research in extrathyroidal malignancies, focusing on breast and
      urological cancer, emphasizing the most relevant developments that may have
      clinical impact. CONCLUSIONS: Given the recent progress in the study of NIS
      regulation as molecular basis for new therapeutic approaches in extrathyroidal
      cancers, particular attention is given to studies regarding the relationship
      between NIS and clinical-pathological aspects of the tumors and the regulation of
      NIS expression in the experimental models.

PMID- 24884808
TI  - Incidences and clinical outcomes of acute kidney injury in ICU: a prospective
      observational study in Sri Lanka.
AB  - BACKGROUND: Acute kidney injury (AKI) is a common and a serious complication
      among patients admitted to intensive care units (ICUs), and has been the focus of
      many studies leading to recent advances in diagnosis and classification. The
      incidence and outcome of AKI in Sri Lankan ICUs is largely unknown. The aim of
      this study was to describe the incidence, severity and outcome of AKI among
      patients admitted to the medical ICU, National Hospital, Colombo, Sri Lanka
      (NHSL). METHODS: Patients admitted to the medical ICU, NHSL, over a period of 6
      months were studied prospectively.Standard demographic, physiological and
      clinical data were collected. Severity of illness was assessed using SOFA
      (Sequential Organ Failure Assessment) score. Diagnosis of AKI was based on Acute
      Kidney Injury Network (AKIN) criteria. RESULTS: Of 212 patients screened, 108
      satisfied the inclusion criteria; males 67(61.5%); mean age 47.8 years(SD 19.4,
      range 12-94). Mean duration of ICU stay was 11.6 days (SD 10.6, range 2-55).
      Eighty one (75.0%) received mechanical ventilation. Forty nine (45.4%) had
      sepsis. ICU mortality was 38.9% and AKI was present in 60.2%. The majority of AKI
      patients (38, 58.5%) had AKI stage 3. Patients with AKI were at higher risk of
      death (p < 0.01). Neither age, gender, nor the presence of co-morbidities were
      associated with increased risk of AKI. Patients with AKI had significantly longer
      ICU stay (Log-Rank Chi Square: 23.186, p < 0.0001). Both the incidence of AKI and
      ICU mortality were higher in patients with SOFA scores over 9 (Pearson Chi-Square
      7.581, p = 0.006, and 11.288, p = 0.001 respectively). CONCLUSIONS: The incidence
      of AKI is high at 60% among our ICU patients, and those with AKI had higher
      mortality and longer duration of ICU stay. Age, gender or the presence of co
      morbidities was not associated with a higher risk of AKI. Patients with SOFA
      scores over 9 within the first 24 hours were more likely to develop AKI and had
      higher risk of death.

PMID- 24884809
TI  - Nutlin-3 overcomes arsenic trioxide resistance and tumor metastasis mediated by
      mutant p53 in Hepatocellular Carcinoma.
AB  - BACKGROUND: Arsenic trioxide has been demonstrated as an effective anti-cancer
      drug against leukemia and solid tumors both in vitro and in vivo. However, recent
      phase II trials demonstrated that single agent arsenic trioxide was poorly
      effective against hepatocellular carcinoma (HCC), which might be due to drug
      resistance. METHODS: Mutation detection of p53 gene in arsenic trioxide resistant
      HCC cell lines was performed. The therapeutic effects of arsenic trioxide and
      Nutlin-3 on HCC were evaluated both in vitro and in vivo. A series of experiments
      including MTT, apoptosis assays, co-Immunoprecipitation, siRNA transfection,
      lentiviral infection, cell migration, invasion, and epithelial-mesenchy-mal
      transition (EMT) assays were performed to investigate the underlying mechanisms.
      RESULTS: The acquisition of p53 mutation contributed to arsenic trioxide
      resistance and enhanced metastatic potential of HCC cells. Mutant p53 (Mutp53)
      silence could re-sensitize HCC resistant cells to arsenic trioxide and inhibit
      the metastatic activities, while mutp53 overexpression showed the opposite
      effects. Neither arsenic trioxide nor Nutlin-3 could exhibit obvious effects
      against arsenic trioxide resistant HCC cells, while combination of them showed
      significant effects. Nutlin-3 can not only increase the intracellular arsenicals
      through inhibition of p-gp but also promote the p73 activation and mutp53
      degradation mediated by arsenic trioxide. In vivo experiments indicated that
      Nutlin-3 can potentiate the antitumor activities of arsenic trioxide in an
      orthotopic hepatic tumor model and inhibit the metastasis to lung. CONCLUSIONS:
      Acquisitions of p53 mutations contributed to the resistance of HCC to arsenic
      trioxide. Nutlin-3 could overcome arsenic trioxide resistance and inhibit tumor
      metastasis through p73 activation and promoting mutant p53 degradation mediated
      by arsenic trioxide.

PMID- 24884810
TI  - GO2MSIG, an automated GO based multi-species gene set generator for gene set
      enrichment analysis.
AB  - BACKGROUND: Despite the widespread use of high throughput expression platforms
      and the availability of a desktop implementation of Gene Set Enrichment Analysis
      (GSEA) that enables non-experts to perform gene set based analyses, the
      availability of the necessary precompiled gene sets is rare for species other
      than human. RESULTS: A software tool (GO2MSIG) was implemented that combines data
      from various publicly available sources and uses the Gene Ontology (GO) project
      term relationships to produce GSEA compatible hierarchical GO based gene sets for
      all species for which association data is available. Annotation sources include
      the GO association database (which contains data for over 200000 species), the
      Entrez gene2go table, and various manufacturers' array annotation files. This
      enables the creation of gene sets from the most up-to-date annotation data
      available. Additional features include the ability to restrict by evidence code,
      to remap gene descriptors, to filter by set size and to speed up repeat queries
      by caching the GO term hierarchy. Synonymous GO terms are remapped to the version
      preferred by the GO ontology supplied. The tool can be used in standalone form,
      or via a web interface. Prebuilt gene set collections constructed from the
      September 2013 GO release are also available for common species including human.
      In contrast human GO based sets available from the Broad Institute itself date
      from 2008. CONCLUSIONS: GO2MSIG enables the bioinformatician and non
      bioinformatician alike to generate gene sets required for GSEA analysis for
      almost any organism for which GO term association data exists. The output gene
      sets may be used directly within GSEA and do not require knowledge of programming
      languages such as Perl, R or Python. The output sets can also be used with other
      analysis software such as ErmineJ that accept gene sets in the same format.
      Source code can be downloaded and installed locally from
      http://www.bioinformatics.org/go2msig/releases/ or used via the web interface at
      http://www.go2msig.org/cgi-bin/go2msig.cgi.

PMID- 24884811
TI  - Multicentre consensus recommendations for skin care in inherited epidermolysis
      bullosa.
AB  - BACKGROUND: Inherited epidermolysis bullosa (EB) comprises a highly heterogeneous
      group of rare diseases characterized by fragility and blistering of skin and
      mucous membranes. Clinical features combined with immunofluorescence antigen
      mapping and/or electron microscopy examination of a skin biopsy allow to define
      the EB type and subtype. Molecular diagnosis is nowadays feasible in all EB
      subtypes and required for prenatal diagnosis. The extent of skin and mucosal
      lesions varies greatly depending on EB subtype and patient age. In the more
      severe EB subtypes lifelong generalized blistering, chronic ulcerations and
      scarring sequelae lead to multiorgan involvement, major morbidity and life
      threatening complications. In the absence of a cure, patient management remains
      based on preventive measures, together with symptomatic treatment of cutaneous
      and extracutaneous manifestations and complications. The rarity and complexity of
      EB challenge its appropriate care. Thus, the aim of the present study has been to
      generate multicentre, multidisciplinary recommendations on global skin care
      addressed to physicians, nurses and other health professionals dealing with EB,
      both in centres of expertise and primary care setting. METHODS: Almost no
      controlled trials for EB treatment have been performed to date. For this reason,
      recommendations were prepared by a multidisciplinary team of experts from
      different European EB centres based on available literature and expert opinion.
      They have been subsequently revised by a panel of external experts, using an
      online-modified Delphi method to generate consensus. RESULTS: Recommendations are
      reported according to the age of the patients. The major topics treated comprise
      the multidisciplinary approach to EB patients, global skin care including wound
      care, management of itching and pain, and early diagnosis of squamous cell
      carcinoma. Aspects of therapeutic patient education, care of disease burden and
      continuity of care are also developed. CONCLUSION: The recommendations are
      expected to be useful for daily global care of EB patients, in particular in the
      community setting. An optimal management of patients is also a prerequisite to
      allow them to benefit from the specific molecular and cell-based treatments
      currently under development.

PMID- 24884812
TI  - Assessment of stigma in patients with cystic fibrosis.
AB  - BACKGROUND: Research that explores stigma in Cystic Fibrosis (CF) is limited.
      Productive cough, repeated lung infections, and periods of serious illness
      requiring hospitalizations are among common symptoms of CF. These symptoms may
      cause a negative perception by others. We developed a CF-specific Stigma Scale
      and tested its psychometric properties. METHODS: We conducted a focus group with
      11 participants including adult patients with CF (n = 5) and their informal
      caregivers (n = 6). The thematic content of the focus group was analyzed to find
      key themes. We developed a CF-specific Stigma Scale and assessed its psychometric
      properties in a 3-month prospective cohort study of adult CF outpatients (n =
      45). RESULTS: Stigma emerged as consistent concern for people living and caring
      for those with CF, affecting both patients' lives and health through the focus
      group. Using the newly developed CF Stigma scale, the mean baseline score was
      16.6 (SD = 4.5, Range = 10-25). The CF Stigma Scale demonstrated robust
      psychometric properties: 1) Internal consistency: alpha = 0.79; 2) Mean inter
      item correlation: 0.30 with good test-retest reliability; 3) Convergent validity:
      Positive associations with depression, severity of CF symptoms and anxiety;
      negative associations with validated quality of life scores were observed.
      CONCLUSIONS: Stigma is measurable and significantly impacts the lives of CF
      patients. Further research should investigate the role of stigma in patients
      living with CF.

PMID- 24884813
TI  - Multimorbidity and long-term care dependency--a five-year follow-up.
AB  - BACKGROUND: Not only single, but also multiple, chronic conditions are becoming
      the normal situation rather than the exception in the older generation. While
      many studies show a correlation between multimorbidity and various health
      outcomes, the long-term effect on care dependency remains unclear. The objective
      of this study is to follow up a cohort of older adults for 5 years to estimate
      the impact of multimorbidity on long-term care dependency. METHODS: This study is
      based on claims data from a German health insurance company. We included 115,203
      people (mean age: 71.5 years, 41.4% females). To identify chronic diseases and
      multimorbidity, we used a defined list of 46 chronic conditions based on ICD-10
      codes. Multimorbidity was defined as three or more chronic conditions from this
      list. The main outcome was "time until long-term care dependency". The follow-up
      started on January 1st, 2005 and lasted for 5 years until December 31st, 2009. To
      evaluate differences between those with multimorbidity and those without, we
      calculated Kaplan-Meier curves and then modeled four distinct Cox proportional
      hazard regressions including multimorbidity, age and sex, the single chronic
      conditions, and disease clusters. RESULTS: Mean follow-up was 4.5 years. People
      with multimorbidity had a higher risk of becoming care dependent (HR: 1.85, CI
      1.78-1.92). The conditions with the highest risks for long-term care dependency
      are Parkinson's disease (HR: 6.40 vs. 2.68) and dementia (HR: 5.70 vs. 2.27).
      Patients with the multimorbidity pattern "Neuropsychiatric disorders" have a 79%
      higher risk of care dependency. CONCLUSIONS: The results should form the basis
      for future health policy decisions on the treatment of patients with multiple
      chronic diseases and also show the need to introduce new ways of providing long
      term care to this population. A health policy focus on chronic care management as
      well as the development of guidelines for multimorbidity is crucial to secure
      health services delivery for the older population.

PMID- 24884814
TI  - A panel of tumor markers, calreticulin, annexin A2, and annexin A3 in upper tract
      urothelial carcinoma identified by proteomic and immunological analysis.
AB  - BACKGROUND: Upper tract urothelial carcinoma (UTUC) is a tumor with sizable
      metastases and local recurrence. It has a worse prognosis than bladder cancer.
      This study was designed to investigate the urinary potential tumor markers of
      UTUC. METHODS: Between January 2008 and January 2009, urine was sampled from 13
      patients with UTUC and 20 healthy adults. The current study identified biomarkers
      for UTUC using non-fixed volume stepwise weak anion exchange chromatography for
      fractionation of urine protein prior to two-dimensional gel electrophoresis.
      RESULTS: Fifty five differential proteins have been determined by comparing with
      the 2-DE maps of the urine of UTUC patients and those of healthy people. Western
      blotting analysis and immunohistochemistry of tumor tissues and normal tissues
      from patients with UTUC were carried out to further verify five possible UTUC
      biomarkers, including zinc-alpha-2-glycoprotein, calreticulin, annexin A2,
      annexin A3 and haptoglobin. The data of western blot and immunohistochemical
      analysis are consistent with the 2-DE data. Combined the experimental data in the
      urine and in tumor tissues collected from patients with UTUC, the crucial over
      expressed proteins are calreticulin, annexin A2, and annexin A3. CONCLUSIONS:
      Calreticulin, annexin A2, and annexin A3 are very likely a panel of biomarkers
      with potential value for UTUC diagnosis.

PMID- 24884816
TI  - A superfluorinated molecular probe for highly sensitive in vivo(19)F-MRI.
AB  - (19)F-MRI offers unique opportunities to image diseases and track cells and
      therapeutic agents in vivo. Herein we report a superfluorinated molecular probe,
      herein called PERFECTA, possessing excellent cellular compatibility, and whose
      spectral properties, relaxation times, and sensitivity are promising for in vivo
      (19)F-MRI applications. The molecule, which bears 36 equivalent (19)F atoms and
      shows a single intense resonance peak, is easily synthesized via a simple one
      step reaction and is formulated in water with high stability using trivial
      reagents and methods. 

PMID- 24884815
TI  - Relationship amongst teratozoospermia, seminal oxidative stress and male
      infertility.
AB  - BACKGROUND: Spermatozoa morphology is an important and complex characteristic of
      the fertilization capacity of male germ cells. Morphological abnormalities have
      been observed to be accompanied by reactive oxygen species (ROS) overproduction
      and further damage to spermatozoa, ultimately leading to infertility. Therefore,
      this study aimed to examine the relationship between seminal ROS production and
      sperm morphology in infertile teratozoospermic patients as well as in healthy men
      of proven and unproven fertility. METHODS: Semen samples were collected from 79
      patients classified as teratozoospermic and 56 healthy donors (control). Standard
      semen analysis was performed and spermatozoa morphology was assessed according to
      the WHO 2010 guidelines. Seminal ROS was measured by chemiluminescence assay.
      Receiver operating characteristic (ROC) curves were generated, and sensitivity,
      specificity, cutoff value and area under curve (AUC) were determined. RESULTS:
      Sperm morphology was significantly poor in the Teratozoospermic Group compared
      with the 3 Donor Groups (P < 0.05). Significantly higher levels of ROS
      (RLU/sec/106 sperm) were seen in the Teratozoospermic group (145.4 (41.5; 555.4)
      compared to the Donor Groups: All Donors (64.8 (21.1; 198.2), Proven Donors (58.8
      (14.2; 79.2) and Proven Donors < 2 years (58.8 (14.2; 79.2) (P < 0.05). ROS
      correlated negatively with sperm concentration in the All Donor group (r = 
      0.354; P = 0.021) as well as in the Teratozospermic group (r -0.356; P = 0.002).
      Using ROC analysis, we established the cutoff values for concentration,
      morphology and ROS. CONCLUSIONS: The incidence of teratozoospermia may be
      directly related to the overproduction of seminal ROS. Therefore, besides sperm
      concentration and motility, spermatozoa morphology should receive an equally
      important consideration in the overall assessment of male fertility.

PMID- 24884817
TI  - Impact of heparin and short term anesthesia on the quantification of cytokines in
      laboratory mouse plasma.
AB  - BACKGROUND: Studies have reported that heparin may be unsuitable as an
      anticoagulant in human plasma samples when quantifying cytokines using multiplex
      bead array assays. For mouse samples, multiplex assays have been validated for
      serum and EDTA-plasma, but it remains to be elucidated whether heparin influences
      the quantification of cytokines, and if so - to what extent. Furthermore,
      laboratory mice are often anesthetized for blood sampling, which causes acute
      stress that may influence circulating cytokine concentrations and thus bias
      experimental results. The objectives of the present study were to identify
      whether specific cytokine concentrations varied between heparin-plasma, serum,
      and EDTA-plasma, and whether short isoflurane anesthesia would influence the
      concentrations of these cytokines in the circulation. Twenty-three acute phase
      and pro-inflammatory cytokines were quantified in matched serum, EDTA-plasma, and
      heparin-plasma samples from anesthetized and unanesthetized male NMRI mice using
      a multiplex assay. In addition, samples from unanesthetized mice were spiked with
      three levels of heparin. RESULTS: The concentrations of five out of 23 cytokines
      were significantly different between sample types, but only one cytokine (IL-17A)
      differed between heparin-plasma and serum. When further spiking the heparin
      plasma with increasing concentrations of heparin, there was a significant effect
      on 11 cytokines, where the cytokine recovery could be correlated to the heparin
      concentration for ten of these cytokines. Anesthesia resulted in lower
      concentrations of G-CSF, but had no significant impact on the concentrations of
      the other 22 cytokines. CONCLUSION: In mice, heparin seems like a suitable
      anticoagulant for obtaining plasma for multiplex assays for the cytokines IL
      1alpha, IL-1beta, IL-2, IL-6, IL-9, IL-12p40, IL-12p70, IL-13, G-CSF, GM-CSF, IFN
      gamma, KC, MCP-1, MIP-1alpha, MIP-1beta, RANTES and TNFalpha, but an effect of
      heparin in high concentrations should be considered for the cytokines IL-9, IL
      12p40, IL-12p70, KC, MCP-1, MIP-1beta and RANTES. Short isoflurane anesthesia had
      significant impact on G-CSF, but none of the other cytokines.

PMID- 24884818
TI  - Effect of time factors on the mortality in brittle hip fracture.
AB  - OBJECTIVE: The aim of this research is to study the effect of time factors on the
      mortality of brittle hip fracture. METHODS: The data of 705 patients of hip
      fracture hospitalized at our department from 2010 to 2012 were reviewed. Among
      them, 499 cases undergoing surgical operation over the age of 50 were followed
      up, and 250 cases had valid follow-up records. The effects of the time from
      injury to operation, the time from injury to hospitalization and the time from
      hospitalization to operation on the mortality were analyzed. RESULTS: The average
      duration of follow-up was 21.37 +/- 9.77 months. There were 198 cases which were
      followed up for over 12 months. Nine patients died within 3 months after the hip
      fracture surgery, and 13 patients died within 1 year. A total of 25 patients died
      during the follow-up. The survival rate of patients with the interval from injury
      to surgery longer than 5 days was lower than that of patients with the interval
      less than or equal to 5 days (p = 0.014). The survival rate of patients with the
      interval from injury to hospitalization longer than 2 days was lower than that of
      patients with the interval from injury to hospitalization less than or equal to 2
      days (p = 0.003). There was no statistical significance in the survival rate
      between patients with the interval from hospitalization to surgery longer than 3
      days and that of patients with the interval from hospitalization to surgery less
      than or equal to 3 days (p = 0.973). CONCLUSION: The operational delay,
      especially the delay of time from injury to hospitalization, is an important
      factor affecting the early mortality of hip fracture. The delay of time from
      hospitalization to operation is mainly due to the consideration of the patients'
      situation and has no effect on early mortality.

PMID- 24884819
TI  - Efficacy of a mesenchymal stem cell loaded surgical mesh for tendon repair in
      rats.
AB  - OBJECTIVES: The purpose of this study was to investigate the efficacy of a
      composite surgical mesh for delivery of mesenchymal stem cells (MSCs) in tendon
      repair. METHODS: The MSC-loaded mesh composed of a piece of conventional surgical
      mesh and a layer of scaffold, which supported MSC-embedded alginate gel. A 3-mm
      defect was surgically created at the Achilles tendon-gastrocnemius/soleus
      junction in 30 rats. The tendon defects were repaired with either 1) MSC-loaded
      mesh; or 2) surgical mesh only; or 3) routine surgical suture. Repaired tendons
      were harvested at days 6 and 14 for histology, which was scored on the bases of
      collagen organization, vascularity and cellularity, and immunohistochemisty of
      types I and III collagen. RESULTS: In comparison with the other two repair types,
      at day 6, the MSC-loaded mesh significantly improved the quality of the repaired
      tendons with dense and parallel collagen bundles, reduced vascularity and
      increased type I collagen. At day 14, the MSC-loaded mesh repaired tendons had
      better collagen formation and organization. CONCLUSION: The MSC-loaded mesh
      enhanced early tendon healing, particularly the quality of collagen bundles.
      Application of the MSC-loaded mesh, as a new device and MSC delivery vehicle, may
      benefit to early functional recovery of the ruptured tendon.

PMID- 24884820
TI  - Structure-activity relationship study of trifluoromethylketone inhibitors of
      insect juvenile hormone esterase: comparison of several classification methods.
AB  - Juvenile hormone esterase (JHE) plays a key role in the development and
      metamorphosis of holometabolous insects. Its inhibitors could possibly be
      targeted for insect control. Conversely, JHE may also be involved in endocrine
      disruption by xenobiotics, resulting in detrimental effects in beneficial
      insects. There is therefore a need to know the structural characteristics of the
      molecules able to monitor JHE activity, and to develop SAR and QSAR studies to
      estimate their effectiveness. For a large diverse population of 181
      trifluoromethylketones (TFKs) - the most potent JHE inhibitors known to date - we
      recently proposed a binary classification (active/inactive) using a support
      vector machine and Codessa structural descriptors. We have now examined, using
      the same data set and with the same descriptors, the applicability and
      performance of five other machine learning approaches. These have been shown able
      to handle high dimensional data (with descriptors possibly irrelevant or
      redundant) and to cope with complex mechanisms, but without delivering explicit
      directly exploitable models. Splitting the data into five batches (training set
      80%, test set 20%) and carrying out leave-one-out cross-validation, led to good
      results of comparable performance, consistent with our previous support vector
      classifier (SVC) results. Accuracy was greater than 0.80 for all approaches. A
      reduced set of 15 descriptors common to all the investigated approaches showed
      good predictive ability (confirmed using a three-layer perceptron) and gives some
      clues regarding a mechanistic interpretation. 

PMID- 24884821
TI  - Sweetened beverage consumption and the risk of hyperuricemia in Mexican adults: a
      cross-sectional study.
AB  - BACKGROUND: The prevalence of hyperuricemia has doubled worldwide during the last
      few decades. The substantial increase in sweetened beverage (SB) consumption has
      also coincided with the secular trend of hyperuricemia. Recent studies do show
      that the consumption of SB can induce hyperuricemia. However, the association
      between SB and hyperuricemia remains unclear. The aim of this study was to
      evaluate the association between SB consumption and levels of uric acid in
      Mexican adults. METHODS: We performed a cross-sectional analysis of data from
      selected adults participating in the baseline assessment of the Health Workers
      Cohort Study. A total of 6,705 participants of both sexes between ages 18 and 70
      years were included. SB intake was estimated using a validated semi-quantitative
      food frequency questionnaire. Biochemical and anthropometric information was
      collected using standard procedures. Hyperuricemia was defined as uric acid
      levels >= 7.0 mg/dL in men and >= 5.8 mg/dL in women. The association of interest
      was assessed by multiple logistic regression models. RESULTS: The odds ratios
      (OR) for hyperuricemia in men who consume 0.5-1 SB/day was 1.59 (95% CI; 1.05
      2.40) and 2.29 (95% CI; 1.55-3.38) for those who consume >=3 SB/day when compared
      to men who consume less than half a SB/day. In women, the OR for hyperuricemia
      for those who consume >1.0- < 3.0 SB/day was 1.33 (95% CI; 1.04-1.70) and 1.35
      (95% CI; 1.04-1.75) for those who consume >=3 SB/day when compared to women who
      consume less than half a SB/day, independent of other covariables. Men and women
      with high SB consumption and a body mass index (BMI) >= 25 Kg/m2 had greater risk
      for hyperuricemia than men and women with low SB consumption and normal BMI < 25
      Kg/m2. CONCLUSIONS: Our findings suggest that the consumption of SB is associated
      with an increased risk of hyperuricemia in Mexican adults. However, longitudinal
      research is needed to confirm the association between SB intake and
      hyperuricemia.

PMID- 24884822
TI  - A replication study confirms the association of GWAS-identified SNPs at MICB and
      PLCE1 in Thai patients with dengue shock syndrome.
AB  - BACKGROUND: Dengue shock syndrome (DSS), a severe life-threatening form of dengue
      infection, mostly occurs in children. A recent genome wide association study
      (GWAS) identified two SNPs, rs3132468 of major histocompatibility complex class I
      polypeptide-related sequence B (MICB) and rs3765524 of phospholipase C, epsilon 1
      (PLCE1), associated with DSS in Vietnamese children. In this study, to examine
      whether an identical association is found in a different population, the
      association of these two SNPs with DSS was assessed in Thai children with dengue.
      METHODS: The rs3132468 and rs3765524 SNPs were genotyped in 917 Thai children
      with dengue: 76 patients with DSS and 841 patients with non-DSS. The allele
      frequencies were compared between DSS and non-DSS groups by one-sided Fisher's
      exact test. The association of rs3132468 and rs3765524 with the mRNA expression
      levels of MICB and PLCE1 were assessed in EBV-transformed lymphoblastoid cell
      lines. RESULTS: The reported DSS-risk alleles were significantly associated with
      DSS in Thai patients with dengue (one-sided P = 0.0213 and odds ratio [OR] = 1.58
      for rs3132468-C and one-sided P = 0.0252 and OR = 1.49 for rs3765524-C). The
      rs3132468-C allele showed a significant association with lower mRNA level of MICB
      (P = 0.0267), whereas the rs3765524-C allele did not. These results imply that
      the MICB molecule may play an important role in the prevention of DSS in dengue
      infection. CONCLUSIONS: Together with previous association studies, we conclude
      that rs3132468-C at MICB and rs3765524-C at PLCE1 confer risk of DSS in Southeast
      Asians.

PMID- 24884824
TI  - Learning through loss: implementing lossography narratives in death education.
AB  - Students may have a greater willingness to discuss issues of death and loss
      through written assignments; however, there is little guidance for instructors
      regarding how to manage these sensitive assignments, nor how students benefit
      from them. The authors implemented and evaluated a "lossography" assignment in an
      undergraduate thanatology course in which students wrote about their losses and
      anonymously shared these narratives with their classmates. Although many themes
      of loss emerged, the most frequently reported significant loss was death of a
      grandparent. Additionally, most significant losses occurred in
      childhood/adolescence. Prominent themes related to student learning included
      gaining self-awareness, knowledge about grief responses, and compassion for
      others. Students (N = 64) also completed a survey reflecting on their course
      learning. Of all aspects of course delivery, 44% identified the lossography as
      the most beneficial, whereas 97% recommended this assignment for future students.
      The implications of the assignment for death education are also discussed. 

PMID- 24884823
TI  - Phenolic contents, antioxidant and anticholinesterase potentials of crude
      extract, subsequent fractions and crude saponins from Polygonum hydropiper L.
AB  - BACKGROUND: We investigated Polygonum hydropiper L. (P. hydropiper) for phenolic
      contents, antioxidant, anticholinesterase activities, in an attempt to
      rationalize its use in neurological disorders. METHODS: Plant crude extract
      (Ph.Cr), its subsequent fractions: n-hexane (Ph.Hex), chloroform (Ph.Chf), ethyl
      acetate (Ph.EtAc), n-Butanol (Ph.Bt), aqueous (Ph.Aq) and saponins (Ph.Sp) were
      evaluated for 1,1-diphenyl,2-picrylhydrazyl (DPPH), 2,2-azinobis[3
      ethylbenzthiazoline]-6-sulfonic acid (ABTS) free radical scavenging potential.
      Further, acetylcholinesterase (AChE) & butyrylcholinesterase (BChE) inhibitory
      activities were performed using Ellman's assay. Moreover, total phenolic contents
      of plant extracts were determined and expressed in mg of gallic acid equivalent
      per gram of dry sample (mg GAE/g dry weight). RESULTS: Among different fractions,
      Ph.Cr (90.82), Ph.Chf (178.16), Ph.EtAc (203.44) and Ph.Bt (153.61) exhibited
      high phenolic contents. All fractions showed concentration dependent DPPH
      scavenging activity, with Ph.EtAc 71.33% (IC50 15 MUg/ml), Ph.Bt 71.40% (IC50 3
      MUg/ml) and Ph.Sp 71.40% (IC50 35 MUg/ml) were most potent. The plant extracts
      exhibited high ABTS scavenging ability i.e. Ph.Bt (91.03%), Ph.EtAc (90.56%),
      Ph.Sp (90.84%), Ph.Aq (90.56%) with IC50<0.01 MUg/ml. All fractions showed
      moderate to high AChE inhibitory activity as; Ph.Cr, 86.87% (IC50 330 MUg/ml),
      Ph.Hex, 87.49% (IC50 35 MUg/ml), Ph.Chf, 84.76% (IC50 55 MUg/ml), Ph.Sp, 87.58%
      (IC50 108 MUg/ml) and Ph.EtAc 79.95% (IC50 310 MUg/ml) at 1 mg/ml). Furthermore
      the BChE inhibitory activity was most prominent in Ph.Hex 90.30% (IC50 40
      MUg/ml), Ph.Chf 85.94% (IC50 215 MUg/ml), Ph.Aq 87.62% (IC50 3 MUg/ml) and
      Ph.EtAc 81.01% (IC50 395 MUg/ml) fractions. CONCLUSIONS: In this study, for the
      first time, we determined phenolic contents, isolated crude saponins,
      investigated antioxidant and anticholinestrase potential of P. hydropiper
      extracts. The results indicate that P. hydropiper is enriched with potent
      bioactive compounds and warrant further investigation by isolation and structural
      elucidation to find novel and affordable compounds for the treatment of various
      neurological disorders.

PMID- 24884825
TI  - Increased genetic diversity of ADME genes in African Americans compared with
      their putative ancestral source populations and implications for
      pharmacogenomics.
AB  - BACKGROUND: African Americans have been treated as a representative population
      for African ancestry for many purposes, including pharmacogenomic studies.
      However, the contribution of European ancestry is expected to result in
      considerable differences in the genetic architecture of African American
      individuals compared with an African genome. In particular, the genetic admixture
      influences the genomic diversity of drug metabolism-related genes, and may cause
      high heterogeneity of drug responses in admixed populations such as African
      Americans. RESULTS: The genomic ancestry information of African-American (ASW)
      samples was obtained from data of the 1000 Genomes Project, and local ancestral
      components were also extracted for 32 core genes and 252 extended genes, which
      are associated with drug absorption, distribution, metabolism, and excretion
      (ADME) genes. As expected, the global genetic diversity pattern in ASW was
      determined by the contributions of its putative ancestral source populations, and
      the whole profiles of ADME genes in ASW are much closer to those in YRI than in
      CEU. However, we observed much higher diversity in some functionally important
      ADME genes in ASW than either CEU or YRI, which could be a result of either
      genetic drift or natural selection, and we identified some signatures of the
      latter. We analyzed the clinically relevant polymorphic alleles and haplotypes,
      and found that 28 functional mutations (including 3 missense, 3 splice, and 22
      regulator sites) exhibited significantly higher differentiation between the three
      populations. CONCLUSIONS: Analysis of the genetic diversity of ADME genes showed
      differentiation between admixed population and its ancestral source populations.
      In particular, the different genetic diversity between ASW and YRI indicated that
      the ethnic differences in pharmacogenomic studies are broadly existed despite
      that African ancestry is dominant in Africans Americans. This study should
      advance our understanding of the genetic basis of the drug response heterogeneity
      between populations, especially in the case of population admixture, and have
      significant implications for evaluating potential inter-population heterogeneity
      in drug treatment effects.

PMID- 24884826
TI  - Cache-Oblivious parallel SIMD Viterbi decoding for sequence search in HMMER.
AB  - BACKGROUND: HMMER is a commonly used bioinformatics tool based on Hidden Markov
      Models (HMMs) to analyze and process biological sequences. One of its main
      homology engines is based on the Viterbi decoding algorithm, which was already
      highly parallelized and optimized using Farrar's striped processing pattern with
      Intel SSE2 instruction set extension. RESULTS: A new SIMD vectorization of the
      Viterbi decoding algorithm is proposed, based on an SSE2 inter-task
      parallelization approach similar to the DNA alignment algorithm proposed by
      Rognes. Besides this alternative vectorization scheme, the proposed
      implementation also introduces a new partitioning of the Markov model that allows
      a significantly more efficient exploitation of the cache locality. Such
      optimization, together with an improved loading of the emission scores, allows
      the achievement of a constant processing throughput, regardless of the innermost
      cache size and of the dimension of the considered model. CONCLUSIONS: The
      proposed optimized vectorization of the Viterbi decoding algorithm was
      extensively evaluated and compared with the HMMER3 decoder to process DNA and
      protein datasets, proving to be a rather competitive alternative implementation.
      Being always faster than the already highly optimized ViterbiFilter
      implementation of HMMER3, the proposed Cache-Oblivious Parallel SIMD Viterbi
      (COPS) implementation provides a constant throughput and offers a processing
      speedup as high as two times faster, depending on the model's size.

PMID- 24884827
TI  - Time to revisit arsenic regulations: comparing drinking water and rice.
AB  - BACKGROUND: Current arsenic regulations focus on drinking water without due
      consideration for dietary uptake and thus seem incoherent with respect to the
      risks arising from rice consumption. Existing arsenic guidelines are a cost
      benefit compromise and, as such, they should be periodically re-evaluated.
      DISCUSSION: Literature data was used to compare arsenic exposure from rice
      consumption relative to exposure arising from drinking water. Standard risk
      assessment paradigms show that arsenic regulations for drinking water should
      target a maximum concentration of nearly zero to prevent excessive lung and
      bladder cancer risks (among others). A feasibility threshold of 3 MUg As l(-1)
      was determined, but a cost-benefit analysis concluded that it would be too
      expensive to target a threshold below 10 MUg As l(-1). Data from the literature
      was used to compare exposure to arsenic from rice and rice product consumption
      relative to drinking water consumption. The exposure to arsenic from rice
      consumption can easily be equivalent to or greater than drinking water exposure
      that already exceeds standard risks and is based on feasibility and cost-benefit
      compromises. It must also be emphasized that many may disagree with the
      implications for their own health given the abnormally high cancer odds expected
      at the cost-benefit arsenic threshold. SUMMARY: Tighter drinking water quality
      criteria should be implemented to properly protect people from excessive cancer
      risks. Food safety regulations must be put in place to prevent higher
      concentrations of arsenic in various drinks than those allowed in drinking water.
      Arsenic concentrations in rice should be regulated so as to roughly equate the
      risks and exposure levels observed from drinking water.